PMID- 15939501
TI  - The use of thiolated polymers as carrier matrix in oral peptide delivery--proof
      of concept.
AB  - It was the aim of this study to develop an oral delivery system for the peptide
      drug antide. The stability of the therapeutic peptide towards gastrointestinal
      peptidases was evaluated. The therapeutic agent and the permeation mediator
      glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine
      conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release
      studies were performed in the dissolution test apparatus according to the
      Pharmacopoeia Europea using the paddle method and demineralized water as release
      medium. In order to avoid mucoadhesion of these delivery systems already in the
      oral cavity and oesophagus tablets were coated with a triglyceride. These tablets
      were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover,
      antide was administered intravenously, subcutaneously and orally in solution.
      Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In
      contrast, antide was rapidly degraded by elastase. Consequently a stomach
      targeted delivery system was designed. Drug release studies demonstrated an
      almost zero-order controlled release of antide over 8 h. In vivo studies
      demonstrated a relative bioavailability of 34.4% for the subcutaneous
      administration. Oral administration of antide in solution led to no detectable
      concentrations of the drug in plasma at all. In contrast, administering antide
      being incorporated in the thiolated polymer resulted in a significant uptake of
      the peptide. The absolute and relative bioavailability was determined to be 1.1%
      and 3.2%, respectively.

PMID- 15939500
TI  - Pluronic block copolymers alter apoptotic signal transduction of doxorubicin in
      drug-resistant cancer cells.
AB  - Pluronic block copolymer P85 (P85) sensitizes multidrug resistant (MDR) cancer
      cells resulting in the increase of cytotoxic activity of antineoplastic agents.
      This effect is attributed to the inhibition of the most clinically relevant drug
      efflux transporter, P-glycoprotein (Pgp), through the combined ATP depletion and
      inhibition of Pgp ATPase activity. The present study elucidates effects of an
      anticancer agent, doxorubicin (Dox), formulated with P85 on drug-induced
      apoptosis in MDR cancer cells. Early and late stages of apoptosis were detected
      by Annexin V and TUNEL methods, respectively. In parallel experiments, the
      expression of genes related to apoptosis, BCL2, BCLXL, BAX, P53, APAF1, Caspase
      3, and Caspase 9, was determined by RT-PCR. The obtained data suggest that
      Dox/P85 formulation induces apoptosis in the resistant cancer cells more
      efficiently than free Dox. The treatment of the cells with Dox alone
      simultaneously activated a proapoptotic signal and an antiapoptotic cellular
      defense. Therefore, the apoptosis induction by Dox was substantially limited. In
      contrast, the treatment of the cells with Dox/P85 formulation significantly
      enhanced the proapoptotic activity of the drug and prevented the activation of
      the antiapoptotic cellular defense. This is likely to result in the stronger
      cytotoxic response of the resistant cells to the Dox/P85 formulation compared to
      the free drug.

PMID- 15939502
TI  - Lessons from the genomes of bifidobacteria.
AB  - The gut microbiota is a complex ecosystem composed of hundreds of different
      bacterial species that altogether play an important role in the physiology of
      their host. In the past few years the complete genome sequence of a number of
      bacterial strains isolated from the human gastrointestinal tract has been
      established including that of Bifidobacterium longum NCC2705 isolated from the
      feces of a healthy infant. Bifidobacteria are among the first species to colonise
      the human gastrointestinal tract and as such are believed to play an important
      role in gut homeostasis and normal development. The genome sequence of NCC2705
      has revealed a number of features that suggest how this bacterium has adapted to
      its environment and that could help understanding how it interacts with its host.
      Here, we review general features of bifidobacteria and illustrate how genome
      based approaches can help us better understand the biology of these organisms.

PMID- 15939503
TI  - Overview on sugar metabolism and its control in Lactococcus lactis - the input
      from in vivo NMR.
AB  - The wide application of lactic acid bacteria in the production of fermented foods
      depends to a great extent on the unique features of sugar metabolism in these
      organisms. The relative metabolic simplicity and the availability of genetic
      tools made Lactococcus lactis the organism of choice to gain insight into
      metabolic and regulatory networks. In vivo nuclear magnetic resonance has proven
      a very useful technique to monitor non-invasively the dynamics of intracellular
      metabolite and co-factor pools following a glucose pulse. Examples of the
      application of this methodology to identify metabolic bottlenecks and regulatory
      sites are presented. The use of this information to direct metabolic engineering
      strategies is illustrated.

PMID- 15939504
TI  - Lactic acid bacteria - Genetics, metabolism and application.

PMID- 15939505
TI  - Bacterial resistance to antibiotics: active efflux and reduced uptake.
AB  - Antibiotic resistance of bacterial pathogens is a fast emerging global crisis and
      an understanding of the underlying resistance mechanisms is paramount for design
      and development of new therapeutic strategies. Permeability barriers for and
      active efflux of drug molecules are two resistance mechanisms that have been
      implicated in various infectious outbreaks of antibiotic-resistant pathogens,
      suggesting that these mechanisms may be good targets for new drugs. The synergism
      of reduced uptake and efflux is most evident in the multiplicative action of the
      outer membrane permeability barrier and active efflux, which results in high
      level intrinsic and/or acquired resistance in many clinically important Gram
      negative bacteria. This review summarizes the current knowledge of these two
      important resistance mechanisms and potential strategies to overcome them. Recent
      advances in understanding the physical structures, function and regulation of
      efflux systems will facilitate exploitation of pumps as new drug targets.

PMID- 15939506
TI  - Estimating the proportion of community-associated methicillin-resistant
      Staphylococcus aureus: two definitions used in the USA yield dramatically
      different estimates.
AB  - The objective of this retrospective study was to compare the prevalence of
      community-associated methicillin-resistant Staphylococcus aureus (CAMRSA) and
      healthcare-associated MRSA (HAMRSA) using healthcare risk factor exposure
      criteria with that obtained using Centers for Disease Control and Prevention
      (CDC) criteria. Cases were defined as CAMRSA or HAMRSA based on the general CDC
      guidelines for nosocomial infections, and then re-assessed with healthcare risk
      factor exposure criteria using a medical chart review. One hundred MRSA cases
      occurred at a mid-Western veterans affairs medical centre from November 2001 to
      November 2003. The proportion of these cases classified as CAMRSA differed
      dramatically when classified by healthcare risk factor exposure criteria (5%)
      compared with CDC nosocomial infection criteria (49%). Estimating the role of
      healthcare-related exposures and developing strategies to control MRSA can be
      markedly affected by the criteria used to determine CAMRSA and HAMRSA.

PMID- 15939507
TI  - Methylobacterium sp. bacteraemia due to a contaminated endoscope.

PMID- 15939508
TI  - Questionnaire to reduce the risk of iatrogenic prion disease transmission.

PMID- 15939509
TI  - Tuning the biological properties of amphipathic alpha-helical antimicrobial
      peptides: rational use of minimal amino acid substitutions.
AB  - In nature, alpha-helical antimicrobial peptides present the small and flexible
      residue glycine at positions 7 or 14 with a significant frequency. Based on the
      sequence of the non-proteinogenic alpha-helical model peptide P1(Aib7), with a
      potent, broad spectrum antimicrobial activity, six peptides were designed by
      effecting a single amino acid substitution to investigate how tuning the
      structural characteristics at position 7 could lead to optimization of
      selectivity without affecting antimicrobial activity against a broad panel of
      multidrug resistant bacterial and yeast indicator strains. The relationship
      between structural features (size/hydrophobicity of the side chain as well as
      conformation and flexibility) and biological activity, in terms of minimum
      inhibitory concentration, membrane permeabilization kinetics and lysis of red
      blood cells are discussed. On conversion of the peptide to proteinogenic
      residues, these principles allowed development of a potent antimicrobial peptide
      with a reduced cytotoxicity. However, while results suggest that both
      hydrophobicity of residue 7 and chain flexibility at this position can be
      modulated to improve selectivity, position 14 is less tolerant of substitutions.

PMID- 15939510
TI  - The suitability of yellow fever and Japanese encephalitis vaccines for
      immunization against West Nile virus.
AB  - Seven volunteers involved in flavivirus studies have been immunized with
      commercial Japanese encephalitis and yellow fever vaccines JE-VAX and YF-VAX.
      Strong homologous and cross-reactive with West Nile virus (WNV) antibody
      responses with titers 1:1600 to 1:51200 were found in all donors. All donors
      developed high levels of yellow fever virus (YFV) and Japanese encephalitis virus
      (JEV) neutralizing antibodies with titers 1:50 to 1:1600 and 1:20 to 1:640,
      respectively, and WNV neutralizing antibodies with titers 1:10 to 1:80. In
      contrast, predominantly YF-specific cell-mediated immunity was detected in all
      immunized donors. Responses to YFV were long lasting, but the anti-JEV humoral
      immunity was found to decrease with time. Cross-reactive anti-WNV responses were
      following the same trend dropping below detectable level at 4 years post
      immunization and sharply coming back after booster immunization with the JE
      vaccine. Thus, immunization with the commercial flavivirus JE vaccine may be
      beneficial for individuals at high risk of exposure to WNV, such as personnel
      involved in WN research.

PMID- 15939511
TI  - Chernobyl radioactivity persists in reindeer.
AB  - Transfer of 137Cs in the soil-plant/lichen-reindeer food chain was studied in
      central (Ostre Namdal) and southern Norway (Vaga) during 2000-2003. Reindeer from
      these areas have been continuously subjected to countermeasure application since
      the 1986 Chernobyl accident. In both areas no decline in 137Cs concentrations was
      detectable in reindeer slaughtered in autumn since 1995, or in reindeer
      slaughtered in winter since 1998-1999. Seasonal differences in 137Cs
      concentrations in reindeer have been less pronounced in recent years, with 137Cs
      concentrations occasionally higher in autumn than in winter. Soil-to-plant 137Cs
      transfer was significantly higher in Ostre Namdal than in Vaga. Climatic
      influences on lichen growth and abundance, and on soil properties that influence
      the availability of 137Cs for plant uptake, are hypothesized to have a larger
      impact on long-term transfer of radiocaesium in the soil-plant/lichen-reindeer
      food chain than has been previously observed.

PMID- 15939512
TI  - Management of low-flow vascular malformations of upper aero digestive system-role
      of N-butyl cyanoacrylate in peroperative devascularization.
AB  - OBJECTIVES: Low-flow vascular malformations of upper aero digestive system may
      cause difficulty in swallowing and/or breathing and bleeding from these lesions
      may even threaten the life of patient due to risk of aspiration. These lesions
      may require surgical resection with prior devascularization to minimize blood
      loss during surgery. METHODS: Peroperative devascularization of vascular
      malformations was carried in patients of our study group by injecting N-butyl
      cyanoacrylate (NBCA) into vascular malformations using direct puncture technique.
      This was followed by surgical resection of lesion in the same sitting. RESULTS:
      Successful devascularization of vascular malformations in all patients in our
      study group was achieved by injection of NBCA into the lesion by direct puncture
      technique. There was retraction of malformation due to devascularization, good
      plane of cleavage was found during subsequent surgical resection and blood loss
      was minimal. CONCLUSIONS: Low-flow vascular malformations of upper aero digestive
      system can be treated with surgical resection after peroperative
      devascularization. Direct puncture of NBCA into lesion under fluoroscopy control
      is an effective, safe and inexpensive method of devascularization which can be
      carried out by the surgeon in a single sitting.

PMID- 15939513
TI  - Metastasising pleomorphic adenoma of the parotid gland.
AB  - A 33-year-old man had a left superficial parotidectomy for a pleomorphic adenoma.
      He remained well, but 28 years later developed a metastasis in a lymph node in
      the left supraclavicular fossa.

PMID- 15939514
TI  - Plant-specific responses to zinc contamination in a semi-field lysimeter and on
      hydroponics.
AB  - The species Agrostis stolonifera, Brassica napus and Trifolium repens
      representing different ecological strategies, were selected to study the effect
      of Zn contamination on Zn tolerance, uptake and accumulation patterns. Parallel
      tests were carried out with increasing concentrations of Zn in a semi-field
      lysimeter and hydroponics in the climate chamber. A significant reduction in
      biomass production or root length and an increase in shoot Zn concentration was
      observed for all species at increasing external Zn concentrations. However, shoot
      biomass production, Zn tolerance and Zn accumulation differed significantly among
      the tested species. The results in both experimental set-ups were quite similar
      concerning Zn tolerance and accumulation and improved the validity of the
      findings. The rather specific responses of the different plant species to Zn
      contamination interfere with the more generic approach used in risk assessment
      studies. Maximum amounts of Zn in shoot are not likely to cause a risk to
      herbivores.

PMID- 15939515
TI  - Working in London hospitals: perceptions of place in nursing students' employment
      considerations.
AB  - During the past decade, a distinct body of research has started to investigate
      the dynamics between nursing and place. However, despite attention being paid to
      a wide-range of nursing subjects, few studies have engaged with the important
      topic of labour force recruitment. In this context, this study uses a combined
      questionnaire (n=650), interview (n=30) and focus group (n=7) survey of London
      based students, and investigates the complex mix of experiences and perceptions
      that result in hospitals having varying degrees of popularity as potential
      workplaces. The findings suggest experiences and perceptions of institutions
      often gained on clinical placements-to be important, particularly relating to
      feeling valued, the quality of patient care, clinical and educational
      opportunities and team cohesion. These are often combined with experiences and
      perceptions of locality, relating to factors such as cost of living, travel
      considerations and sense of personnel safety. The study demonstrates that place
      is relevant to employment decision-making on multiple scales from wards to
      regions. Furthermore, that perceptions of potential workplaces result from
      engagements with complex mixes of cultural, economic and physical features, many
      of which are the consequences of management. It is argued that in order to
      effectively unpack workplaces, geographical research of nursing labour may
      benefit from researching simultaneously both 'inside' institutions, focusing on
      their dominant cultures of production and sub-cultures, and 'outside', focusing
      on their local urban or rural contexts.

PMID- 15939516
TI  - Local neighbourhood and mental health: evidence from the UK.
AB  - This paper examines the association between neighbourhood and levels and changes
      in common mental disorders. Using data from a large scale nationally
      representative survey of individuals and households (the British Household Panel
      Survey), it locates individuals in their local neighbourhoods. These are defined
      as the nearest 500-800 persons centered around each individual in the survey.
      These 'bespoke' neighbourhoods are characterised according to five dimensions-
      disadvantage, mobility, age, ethnicity and urbanness--derived from factor
      analysis of the census characteristics of the residents of neighbourhoods in
      1991. These dimensions measure characteristics of place that have been argued to
      be associated with mental ill health. The paper estimates multilevel models of
      the level and 5-year changes of common mental disorders (measured by the twelve
      item version of the General Health Questionnaire). Three and two level models are
      estimated, all of which allow for individual and household characteristics that
      may act as confounders of any neighbourhood effect. The results show the extent
      of association between neighbourhood and both levels and changes in mental health
      is limited. Less than one percent of the variance across individuals is at the
      neighbourhood level. The neighbourhood characteristics are not generally
      statistically associated with levels or changes in mental ill health. There is
      some evidence of interaction between neighbourhood characteristics and gender and
      ethnicity, but while statistically significant these interactions are small in
      size compared to the main effects of individual and household characteristics.
      What appears to be important for levels of common mental disorders are the
      observed characteristics of individuals and their households, not of place.

PMID- 15939517
TI  - Treatment of suicide attempters prior to hospital admission.
AB  - OBJECTIVE: Numerous authors have reported serious shortcomings in the treatment
      of suicidal patients. This study examined the treatment suicide attempters
      admitted to a psychiatric hospital in Switzerland had received prior to the
      suicide attempt. METHOD: Thirty-one patients were admitted to this hospital
      within a year, representing 36 suicide attempts, which corresponds to 6.5% of the
      annual admission number. Three of these patients were admitted twice, and one
      patient was admitted three times. Information on previous treatment was collected
      in personal interviews and included medication, and its dosage, at 1 month and 2
      weeks prior to the suicide attempt, and whether the patient had received
      psychotherapy. In addition, details of the psychosocial event and the means of
      the suicide attempt were recorded. RESULTS: Twenty-one patients had been
      prescribed psychotropic drugs in 24 events, but only in 17 events concerning 15
      patients, antidepressants were prescribed prior to hospitalisation.
      Antipsychotics and benzodiazepines were prescribed in 6 and 21 events,
      respectively (including 8 events with hypnotics). None of the patients was
      treated with lithium. In 19 events, 16 patients had received psychotherapy prior
      to admission. In 32 events, psychotropic drugs were used for the suicide attempt.
      CONCLUSION: The findings confirm the undertreatment of patients attempting
      suicide reported by other authors. In spite of the majority of patients being
      under psychiatric care, no adequate pharmacotherapy had been prescribed
      particularly for depressed patients.

PMID- 15939518
TI  - The influence of Serotonin Transporter Promoter Polymorphism (SERTPR) and other
      polymorphisms of the serotonin pathway on the efficacy of antidepressant
      treatments.
AB  - The definition of a genetic liability profile for specific antidepressant
      treatment will soon be available offering considerable help in early detection of
      effective therapy in affective disorders. The search for genetic factors
      predisposing to drug response or side-effects in affective disorders started only
      in the last few years. The efficacy of antidepressant action was associated with
      several polymorphisms, located on coding genes of proteins thought to be involved
      in the different mechanisms of action of antidepressant treatments. Among these,
      gene variants in sequences of serotonin pathway proteins were candidate, both for
      the well known evidence of its involvement in the development of depressive
      symptomathology and for the wide-world use of selective serotonin reuptake
      inhibitors as first choice treatment of depression. A polymorphism in the
      promoter region of the serotonin transporter (SERTPR) was independently
      associated with efficacy for a range of treatments, other polymorphism located on
      the tryptophan hydroxylase gene, 5-HT2a receptor and G-protein beta 3 showed some
      association, while other candidate genes were not associated with treatment
      efficacy. Possible liability genes controlling at least to some extent both acute
      and long-term treatment were identified, and the further objective is to identify
      other candidate genes in order to define individualized treatments according to
      genetic profile in a future. The present paper reviews the pharmacogenetic
      studies published to date, focusing the attention on the serotonergic pathway.

PMID- 15939519
TI  - Changes of smoking behavior and serum adrenocorticotropic hormone, cortisol,
      prolactin, and endogenous opioids levels in nicotine dependence after naltrexone
      treatment.
AB  - This study was done to evaluate the therapeutic effects of naltrexone on smoking
      behaviors and to measure the changing of brain substances for elucidating the
      mode of action by naltrexone. Twenty-five voluntarily participated healthy male
      smokers were randomly assigned to naltrexone group or placebo group for 2 weeks.
      In this study, naltrexone group showed significant reduction in daily cigarette
      consumption amount, the expiratory CO levels, brief questionnaire for smoking
      urge (B-QSU) score, and FTQ score. However, only 2 subjects in naltrexone group
      quitted smoking completely at 4th week. Plasma levels of pituitary hormones
      (ACTH, cortisol, and prolactin) and endogenous opioids (beta-endorphin and
      dynorphin A) were checked weekly before and after the 'provocation and smoking
      coupled' stimulus once in a week for 3 weeks. In naltrexone group, pituitary
      hormones showed upward tendencies even though only the prolactin had statistical
      significance. However, beta-endorphin and dynorphin A were not significantly
      different between the two groups. It was suggested that naltrexone made effects
      on hypothalamo-pituitary-adrenocortical axis activity as well as smoking
      behavior. However, the meaning of these endocrinal changes by naltrexone is not
      conclusive, whether it is beneficial or aversive.

PMID- 15939520
TI  - Anxiety and beta-adrenergic receptor function in a normal population.
AB  - Many studies have shown a close relationship between anxiety and beta-adrenergic
      receptor function in patients with anxiety disorders. This study examined the
      relationship between beta-adrenergic receptor function and anxiety levels in a
      normal population. Subjects for this study included 36 men and 44 women between
      the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26.
      All of them were healthy subjects who had no previous history of medical or
      psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety
      Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose
      (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic
      receptor sensitivity. We also examined correlations between log normalized CD25
      and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men
      was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than
      that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p < 0.001). CD25
      showed negative correlations with STAI state anxiety (r = -0.344, p = 0.002),
      trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was
      positively correlated with BMI (r = 0.423, p < 0.001) and age (r = 0.271, p =
      0.015). In stepwise multiple regression analyses, 34% of the variance in CD25 was
      accounted for by sex, state anxiety, and BMI. The sensitivity of beta-adrenergic
      receptors increased as anxiety levels became higher in a normal population. Thus,
      the relationship between anxiety and beta-adrenergic receptor function in healthy
      subjects may be different from that of patients with anxiety disorders.

PMID- 15939521
TI  - Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive
      schizophrenic patients.
AB  - Several lines of evidence suggest that D-serine, an endogenous agonist of the
      glycine site on the NMDA receptors, might play a role in the pathophysiology of
      schizophrenia. The purpose of this study was to determine whether levels of D-
      and L-serine or D-serine ratio (D-serine/total serine) in cerebrospinal fluid
      (CSF) were altered in first episode and drug-naive schizophrenic patients. The
      CSF levels of D- and L-serine in 25 male first episode and drug-naive
      schizophrenic patients and 17 age-matched male healthy subjects were measured
      using a column-switching high performance liquid chromatography system. The
      percentage of D-serine in the total serine of patients was significantly (z = 
      2.01, p = 0.044) lower than that of controls. This study suggests that synthetic
      or metabolic pathways of D-serine may be abnormal in the brain of drug-naive
      schizophrenic patients, supporting the NMDA receptor dysfunction hypothesis of
      schizophrenia.

PMID- 15939522
TI  - [Surgical management of cutaneous pathomimia. A report case].
AB  - Cutaneous pathomimia is a behaviour disorder witch interest the skin. In some
      cases, self-mutilation can be serious and require a surgical treatment. CASE
      REPORT: A 60 year old woman consults for extensive scar interesting the face and
      the scalp and realising the aspect of burn face in cicatricle level. The
      treatment consisted on excision and skin graft. The patient was addressed to
      Psychodermatology consultation. Authors show the place of plastic surgery in
      management of cutaneous pathomimia.

PMID- 15939523
TI  - Optimal Er:YAG laser energy for preventing enamel demineralization.
AB  - OBJECTIVES: The purpose of this study was to identify the optimal laser energy
      range of Er:YAG laser irradiation for laser-induced caries prevention (LICP).
      METHODS: Twenty-one human non-carious molars were selected. The teeth were
      covered with nail varnish, except two 4 mm x 1 mm windows on both the buccal and
      lingual surfaces. The windows were randomly assigned to groups A, B, C and D,
      receiving no irradiation, 100, 200 and 300 mJ irradiation, respectively. The
      pulse width 10 pps (pulse per second) with a 1.0 mm spot size was used. After the
      laser treatment, each tooth was cut into two halves longitudinally. Then a two
      day pH-cycling was performed, with an 18-hour demineralization followed by a 6
      hour remineralization. Sections of 120 +/- 20 microm in thickness were obtained
      from each window. Lesion depth was measured using polarized light microscope
      coupled with an image analysis software. One-way ANOVA and post-hoc Tukey tests
      were used for evaluation of treatment effects. RESULTS: The laser treatments of
      100 and 200 mJ have demonstrated significant protection of enamel
      demineralization (p = 0.01 and 0.001, respectively), but not the treatment with
      300 mJ (p = 0.106). A smaller lesion depth was observed for the 200 mJ group
      (97.1 microm) than that of the 100 mJ group (105.6 microm). Compared with the
      control, a lesion reduction of 32.78 and 26.93% for the 200 mJ group and the 100
      mJ group were obtained, respectively. CONCLUSION: Caries prevention may be
      achieved by using Er:YAG laser treatment if the optimal range of laser parameters
      for LICP can be employed.

PMID- 15939524
TI  - Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic
      review and meta-analysis of individual patient data advanced bladder cancer (ABC)
      meta-analysis collaboration.
AB  - OBJECTIVES: To update a systematic review and meta-analysis that assesses the
      effect of neoadjuvant chemotherapy in the treatment of patients with invasive
      bladder cancer. METHODS: Following a prespecified protocol, we analysed updated
      individual patient data from all eligible randomised controlled trials that
      compared neoadjuvant chemotherapy plus local treatment with the same local
      treatment alone. RESULTS: Updated results are based on 11 trials, 3005 patients;
      comprising 98% of all patients from known eligible randomised controlled trials.
      We found a significant survival benefit associated with platinum-based
      combination chemotherapy (HR = 0.86, 95% CI 0.77-0.95, p = 0.003). This is
      equivalent to a 5% absolute improvement in survival at 5 years. There was also a
      significant disease-free survival benefit associated with platinum-based
      combination chemotherapy (HR = 0.78 95% CI 0.71-0.86, p < 0.0001), equivalent to
      a 9% absolute improvement at 5 years. CONCLUSIONS: These results provide the best
      available evidence in support of the use of neoadjuvant platinum-based
      combination chemotherapy.

PMID- 15939526
TI  - Re: Montorsi F, Salonia A, Briganti A, Barbieri L, Zanni G, Surdi N, Cestari A,
      Montorsi P, Rigatti P. Vardenafil for the treatment of erectile dysfunction: a
      critical review of the literature based on personal clinical experience. Eur Urol
      2005;47:612-21.

PMID- 15939527
TI  - Evaluation of male sexual function in patients with Lower Urinary Tract Symptoms
      (LUTS) associated with Benign Prostatic Hyperplasia (BPH) treated with a
      phytotherapeutic agent (Permixon), Tamsulosin or Finasteride.
AB  - OBJECTIVES: Sexual function is one of the aspects in the treatment of lower
      urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH)
      that has gained increasing attention. We compared the influence on men's
      sexuality of Permixon, a lipido-sterolic extract of Serenoa Repens, with
      Tamsulosin and Finasteride using a specific validated questionnaire exploring
      patient's sexual functions. METHODS: A database was created comprising patients
      from 3 main double-blind, randomized studies - Permixon vs. Finasteride, Permixon
      vs. Tamsulosin and Permixon 160 mg vs. 320 mg including a total of 2511 patients.
      Three hundred fifty four were on Tamsulosin, 545 on Finasteride and 1612 patients
      on Permixon. LUTS were assessed using the I-PSS questionnaire. Peak flow rates
      and prostate volume were recorded. The MSF-4 questionnaire, including 4 items
      that explore the patient's interest in sex, quality of erection, achievement of
      orgasm and ejaculation, was used across the studies. This questionnaire was
      demonstrated as highly reproducible and both psychometrically and clinically
      valid across different cultures. Correlation coefficients were given to assess
      the linear relationship between continuous variables. RESULTS: At 3 months, there
      were no statistically significant differences between the three treatment groups
      in terms of I-PSS or Qmax evolutions (all p values > 0.05). At 6 months, as
      compared to pretreatment data, there was a slight increase in sexual disorders in
      Tamsulosin (+0.3) and Finasteride (+0.8) treated patients while it slightly
      improved with Permixon therapy (-0.2). Ejaculation disorders were the most
      frequently reported side effects after Tamsulosin or Finasteride (both +0.2 on
      the specific MSF-4 question 4). There was no correlation between the evolution of
      the MSF-4 scores and the evolution in I-PSS neither in patients treated with
      Permixon, Finasteride or Tamsulosin. However, there was a slight correlation
      between the MSF-4 score at baseline and the I-PSS at baseline (r2 = 0.032).
      Although there was a correlation between the MSF-4 and age at baseline (r2 =
      0.1452), there was no correlation between the evolution in MSF-4 during therapy
      and the age of the patients. CONCLUSION: The present study demonstrates that
      Permixon therapy has no negative impact on male sexual function. Both Finasteride
      and Tamsulosin had a slight impact on sexual function, especially on ejaculation,
      although these effects were rare and in line with previous reports about these
      two drugs.

PMID- 15939528
TI  - Biological Age vs. Chronological Age.

PMID- 15939529
TI  - Direct access to the renal artery at the level of treitz ligament during left
      radical laparoscopic transperitoneal nephrectomy.
AB  - PURPOSE: To describe and demonstrate the feasibility of early ligature of the
      renal artery using a direct access to the renal pedicle at the level of the
      Treitz ligament during left transperitoneal radical laparoscopic nephrectomy.
      MATERIALS AND METHODS: A total of 42 patient underwent left transperitoneal
      radical laparoscopic nephrectomies from February 2001 to July 2004. In the first
      consecutive 27 patients (Group A) we performed early ligature with the standard
      technique; in the last consecutive 15 patients (Group B) we attempted the early
      ligature with direct access to the renal artery at the level of the Treitz
      ligament. Comparative analysis was carried out between the two groups examining
      operative times, blood loss, intra and post operative complications,
      postoperative stay. RESULTS: No difference was noted in gender, age and size of
      the lesions (6.2 versus 6.25 cm respectively, p = 0.9) in the two groups. In
      12/15 (80%) of Group B cases we successfully identified and ligated the renal
      artery at the level of the Treitz ligament. In the other 3 cases (20%) we were
      constrained to revert to the more common laparoscopic approach. Mean Operative
      times were 131' in group A versus 137' in group B (p = 0.15). The time required
      to find the renal artery at the level of Treitz ligament in group B was 16' (15'
      30'). No differences were noted between the two groups in terms of blood loss
      (222 cc versus 268 ml, p = 0.4), intraoperative and postoperative complications
      (p = 0.6), postoperative stay (5 days in the two groups, p = 0.9). Mean follow-up
      was average 24 months (15-48) in Group A and average 7 months (3-12) in Group B.
      No complications and no recurrence of disease at CT evaluation were recorded
      neither in Group A nor in Group B. CONCLUSIONS: Radical laparoscopic left side
      nephrectomy with direct access to the renal artery at the level the Treitz
      ligament is technically feasible and safe and reproduces the classic principles
      of radical nephrectomy allowing to perform the procedure without any manipulation
      of the tumor.

PMID- 15939530
TI  - Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta
      analysis of individual patient data Advanced Bladder Cancer (ABC) Meta-analysis
      Collaboration.
AB  - OBJECTIVES: To evaluate the effect of adjuvant chemotherapy in invasive bladder
      cancer. METHODS: : We conducted a systematic review and meta-analysis of updated
      individual patient data from all available randomised controlled trials comparing
      local treatment plus adjuvant chemotherapy versus the same local treatment alone.
      RESULTS: Analyses were based on 491 patients from six trials, representing 90% of
      all patients randomised in cisplatin-based combination chemotherapy trials and
      66% of patients from all eligible trials. The power of this meta-analysis is
      clearly limited. The overall hazard ratio for survival of 0.75 (95% CI 0.60-0.96,
      p = 0.019) suggests a 25% relative reduction in the risk of death for
      chemotherapy compared to that on control. Cox regression suggests that small
      imbalances in patient characteristics do not bias the results in favour of
      chemotherapy. However, the impact of trials that stopped early, of patients not
      receiving allocated treatments or not receiving salvage chemotherapy is less
      clear. CONCLUSIONS: This IPD meta-analysis provides the best evidence currently
      available on the role of adjuvant chemotherapy for invasive bladder cancer.
      However, at present there is insufficient evidence on which to reliably base
      treatment decisions. These results highlight the urgent need for further research
      into the use of adjuvant chemotherapy. The results of appropriately sized
      randomised trials, such as the ongoing EORTC-30994 trial are needed before any
      definitive conclusions can be drawn.

PMID- 15939532
TI  - On the use of multi-objective evolutionary algorithms for the induction of fuzzy
      classification rule systems.
AB  - Extracting comprehensible and general classifiers from data in the form of rule
      systems is an important task in many problem domains. This study investigates the
      utility of a multi-objective evolutionary algorithm (MOEA) for this task. Multi
      objective evolutionary algorithms are capable of finding several trade-off
      solutions between different objectives in a single run. In the context of the
      present study, the objectives to be optimised are the complexity of the rule
      systems, and their fit to the data. Complex rule systems are required to fit the
      data well. However, overly complex rule systems often generalise poorly on new
      data. In addition they tend to be incomprehensible. It is, therefore, important
      to obtain trade-off solutions that achieve the best possible fit to the data with
      the lowest possible complexity. The rule systems produced by the proposed multi
      objective evolutionary algorithm are compared with those produced by several
      other existing approaches for a number of benchmark datasets. It is shown that
      the algorithm produces less complex classifiers that perform well on unseen data.

PMID- 15939533
TI  - The decline in testosterone biosynthesis during male aging: a consequence of
      multiple alterations.
AB  - The decline in blood testosterone concentration during the course of male aging
      results in decreases in many physiological functions. However, the mechanism(s)
      responsible for this decline is not clear. Previous observations have suggested
      the involvement of multiple alterations or defects that inhibit the activities of
      proteins involved in steroidogenesis and result in reduced testosterone
      biosynthesis. Recent studies have demonstrated an age-related increase in
      cyclooxygenase-2 (COX2) activity and its tonic inhibition of steroidogenic acute
      regulatory gene expression and steroidogenesis in rat Leydig cells. These
      findings indicate the presence of a novel mechanism in male aging involving COX2
      and suggest the potential application of COX2 inhibitors or other interventions
      in this mechanism to delay the decline in testosterone biosynthesis in aged
      males.

PMID- 15939534
TI  - HPV 16 E6 sequence variations in Indian patients with cervical neoplasia.
AB  - In a cross-sectional study performed between June 2001 and November 2003, the HPV
      16 E6 gene of 50 women with cervical neoplasia and 20 cytologically normal women
      ('controls') was sequenced following amplification by PCR. The 350T to G variant
      was seen in 35 (70%) of 50 patients' isolates while it was seen in only 3 (15%)
      of the 20 isolates from the 'controls'. The higher occurrence of the 350G variant
      among the patients was statistically significant (P<0.01). Isolates from patients
      were grouped into the European (E), Asian-American (AA) and North-American (NA-1)
      phylogenetic clusters with 46 (92%) belonging to the E cluster. All the 20
      isolates from 'controls' belonged to the E cluster. This study suggests an
      association of the HPV 16 350G variant with a higher risk of cervical neoplasia
      and a predominance of E lineage strains among Indian HPV 16 isolates.

PMID- 15939535
TI  - Studies on salts of 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4,6-trinitroanilino
      benzoic acid (TABA): potential energetic ballistic modifiers.
AB  - The Co/Cu/Ni/Fe salts of 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4,6
      trinitroanilino benzoic acid (TABA) were prepared and characterized during this
      work. All the salts exhibited exothermic decomposition in DSC. The FT-IR spectra
      of the gaseous products evolved during TGA of NTO salts indicated the release of
      NO2 and cleavage of NTO ring during the course of decomposition. Thermal
      decomposition of TABA salts also produced NO2 on decomposition. The transition
      metal salts enhanced the burning rates of AP-HTPB composite propellant evaluated
      during this work. The best catalytic effect was obtained with Fe-NTO salt which
      increased the burning rate to the extent of approximately 80% as well as brought
      down the pressure index (n) to 0.18 (2-9MPa).

PMID- 15939536
TI  - Palmitic and stearic fatty acids induce Alzheimer-like hyperphosphorylation of
      tau in primary rat cortical neurons.
AB  - Epidemiological studies suggest that high fat diets significantly increase the
      risk of Alzheimer's disease (AD). In addition, the AD brain is characterized by
      high fatty acid content compared to that of healthy subjects. Nevertheless, the
      basic mechanism relating elevated fatty acids and the pathogenesis of AD remains
      unclear. The present study examines the role of fatty acids in causing
      hyperphosphorylation of the tau protein, one of the characteristic signatures of
      AD pathology. Hyperphosphorylation of tau disrupts the cell cytoskeleton and
      leads to neuronal degeneration. Here, primary rat cortical neurons and astrocytes
      were treated with saturated free fatty acids (FFAs), palmitic and stearic acids.
      There was no change in the levels of phosphorylated tau in rat cortical neurons
      treated directly with these FFAs. The conditioned media from FFA-treated
      astrocytes, however, caused hyperphosphorylation of tau in the cortical neurons
      at AD-specific phospho-epitopes. Co-treatment of neurons with N-acetyl cysteine,
      an antioxidant, reduced FFA-induced hyperphosphorylation of tau. The present
      results establish a central role of FFAs in causing hyperphosphorylation of tau
      through astroglia-mediated oxidative stress.

PMID- 15939537
TI  - Seronegative conversion in four Neospora caninum-infected cows, with a low rate
      of transplacental transmission.
AB  - Four Neospora-seropositive pregnant cows (prebreeding indirect fluorescent
      antibody (IFA) titers between 1:400 and 1:1600) were confined and observed until
      parturition. All cows gave birth to normal calves. Selected tissues were tested
      for NC by histopathology, immunohistochemical (IHC) and polymerase chain reaction
      (PCR). Parasite isolation was attempted in vero cell cultures. At parturition,
      all cows were seronegative at 1:200 and two of four cows had a titer of 1:100
      when further tested. Three of four calves were not infected, as determined by
      negative results of precolostral serology (1:25 cut-off), histopathology, IHC and
      PCR. One calf was congenitally infected, as shown by the presence of a thick
      walled cyst labelled by IHC in its brain, positive PCR of brain and a
      precolostral IFA titer of 1:100. It was concluded that NC antibody titers may
      drop or convert to seronegative status in chronically infected cows by the time
      of parturition and this finding in four of four cows indicates that this could be
      a common occurrence. Similarly, the finding of an infected calf with a low
      antibody titer indicates that precolostral serology may not be a fool-proof means
      of identifying calves with congenital Neospora caninum infections. These findings
      call into question conclusions of other studies that have estimated rates of
      congenital transmission of this parasite based on serological tests at calving.
      This study is the first confirmed report of congenital NC infection in a calf in
      Thailand.

PMID- 15939538
TI  - Wohlfahrtiosis in sheep and the role of dicyclanil in its prevention.
AB  - Wohlfahrtia magnifica is the main agent of traumatic myiasis in the southern
      Palaearctic zone. It was recorded in outbreak situations in Crete, Greece, for
      the first time in 1999, causing widespread production losses and considerable
      concern in the livestock sectors. Most commonly applied curative insecticides,
      organophosphates and pyrethroids, can kill larvae of W. magnifica, but they do
      not provide long-term protection from infestation or re-infestation, which would
      facilitate wound healing. The objective of the present work was to study the
      seasonal dynamics of sheep wohlfahrtiosis in Crete and to determine the
      prophylactic efficacy of dicyclanil, an insect growth regulator, against natural
      infestations by larvae of W. magnifica. Six sheep flocks were studied, three from
      a semi-intensive husbandry system and three from an extensive husbandry system.
      Two flocks were kept as untreated controls and also were used to study the
      disease dynamics. Dicyclanil was strategically applied just to males and young
      non-milking females in four treatment flocks; milking females in these flocks
      were not treated. The untreated flocks demonstrated seasonal patterns in case
      numbers that were associated with changes in climate and husbandry activities,
      especially reproduction and shearing. Cases were most common on the genitalia
      (60%) and a greater proportion of males than females were infested. The
      prophylactic efficacy of dicyclanil in males was up to 91.3% over the entire
      trial period. Hence the incidence in treated males at 22 weeks, when final
      infestations were recorded, was 5-10% compared to 45-55% in untreated controls.
      Moreover, the application of dicyclanil to a limited number of animals per flock
      (males and non-milking females=c. 15-20% of the flock) significantly reduced the
      incidence of wohlfahrtiosis even in the untreated animals. Hence, final overall
      incidences in the treated flocks ranged from 4.5 to 5.5% compared to 13.3-13.4%
      in the control flocks.

PMID- 15939539
TI  - Ischemic preconditioning prevents protein aggregation after transient cerebral
      ischemia.
AB  - Transient cerebral ischemia leads to protein aggregation mainly in neurons
      destined to undergo delayed neuronal death after ischemia. This study utilized a
      rat transient cerebral ischemia model to investigate whether ischemic
      preconditioning is able to alleviate neuronal protein aggregation, thereby
      protecting neurons from ischemic neuronal damage. Ischemic preconditioning was
      introduced by a sublethal 3 min period of ischemia followed by 48 h of recovery.
      Brains from rats with either ischemic preconditioning or sham-surgery were then
      subjected to a subsequent 7 min period of ischemia followed by 30 min, 4, 24, 48
      and 72 h of reperfusion. Protein aggregation and neuronal death were studied by
      electron and confocal microscopy, as well as by biochemical analyses. Seven
      minutes of cerebral ischemia alone induced severe protein aggregation after 4 h
      of reperfusion mainly in CA1 neurons destined to undergo delayed neuronal death
      (which took place after 72 h of reperfusion). Ischemic preconditioning reduced
      significantly protein aggregation and virtually eliminated neuronal death in CA1
      neurons. Biochemical analyses revealed that ischemic preconditioning decreased
      accumulation of ubiquitin-conjugated proteins (ubi-proteins) and reduced free
      ubiquitin depletion after brain ischemia. Furthermore, ischemic preconditioning
      also reduced redistribution of heat shock cognate protein 70 and Hdj1 from
      cytosolic fraction to protein aggregate-containing fraction after brain ischemia.
      These results suggest that ischemic preconditioning decreases protein aggregation
      after brain ischemia.

PMID- 15939541
TI  - Localization and properties of respiratory neurons in the rostral pons of the
      newborn rat.
AB  - The distribution and discharge pattern of respiratory neurons in the 'pneumotaxic
      center' of the rostral pons in the rat has remained unknown. We performed optical
      recordings and whole-cell patch clamp recordings to clarify respiratory neuron
      activity in the rostral pons of a brainstem-spinal cord preparation from a
      newborn rat. Inspiratory nerve activity was recorded in the 4th cervical nerve
      and used as a trigger signal for optical recordings. Respiratory neuron activity
      was detected in the limited region of the rostral-lateral pons. The main active
      region was presumed to be primarily the Kolliker-Fuse nucleus. The location of
      respiratory neurons was further confirmed by Lucifer Yellow staining after
      conducting whole-cell recordings. From a membrane potential analysis of the
      respiratory neurons in the rostral pons, the respiratory neurons were divided
      into four types: inspiratory neuron (71.9%), pre-inspiratory neuron (5.3%), post
      inspiratory neuron (19.3%), and expiratory neuron (3.5%). A noticeable difference
      between pontine and medullary respiratory neurons was that post-inspiratory
      neurons were more frequently encountered in the pons. Application of a mu-opioid
      agonist, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, transformed the burst pattern
      of post-inspiratory neurons into that of pre-inspiratory neurons. The electrical
      stimulation of the sensory root of the trigeminal nerve induced three types of
      responses in 85% of pontine respiratory neurons: inhibitory postsynaptic
      potentials (42.7%), excitatory postsynaptic potentials (37.7%) and no response
      (15.1%). Our findings provide the first evidence in the rat for the presence of
      respiratory neurons in the rostral pons, with localization in the lateral region
      approximately overlapping with the Kolliker-Fuse nucleus.

PMID- 15939540
TI  - Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12
      [corrected].
AB  - During rapid cell growth the availability of phospholipid precursors like
      cytidine triphosphate and diacylglycerol can become limiting in the formation of
      key membrane constituents like phosphatidylcholine. Uridine, a normal plasma
      constituent, can be converted to cytidine triphosphate in PC12 [corrected] cells
      and intact brain, and has been shown to produce a resulting increase in
      phosphatidylcholine synthesis. To determine whether treatments that elevate
      uridine availability also thereby augment membrane production, we exposed PC12
      [corrected] cells which had been differentiated by nerve growth factor to various
      concentrations of uridine, and measured the numbers of neurites the cells
      produced. After 4 but not 2 days uridine significantly and dose-dependently
      increased the number of neurites per cell. This increase was accompanied by
      increases in neurite branching and in levels of the neurite proteins
      neurofilament M [corrected] and neurofilament 70. Uridine treatment also
      increased intracellular levels of cytidine triphosphate, which suggests that
      uridine may affect neurite outgrowth by enhancing phosphatidylcholine synthesis.
      Uridine may also stimulate neuritogenesis by a second mechanism, since the
      increase in neurite outgrowth was mimicked by exposing the cells to uridine
      triphosphate, and could be blocked by various drugs known to antagonize P2Y
      receptors (suramin; Reactive Blue 2; pyridoxal-phosphate-6-azophenyl-2',4'
      disulfonic acid). Treatment of the cells with uridine or uridine triphosphate
      stimulated their accumulation of inositol phosphates, and this effect was also
      blocked by pyridoxal-phosphate-6-azophenyl-2',4' disulfonic acid. Moreover,
      degradation of nucleotides by apyrase blocked the stimulatory effect of uridine
      on neuritogenesis. Taken together these data indicate that uridine can regulate
      the output of neurites from differentiating PC12 [corrected] cells, and suggest
      that it does so in two ways, i.e. both by acting through cytidine triphosphate as
      a precursor for phosphatidylcholine biosynthesis and through uridine triphosphate
      as an agonist for P2Y receptors.

PMID- 15939542
TI  - Regulation of multiple dopamine signal transduction molecules by retinoids in the
      developing striatum.
AB  - Increasing evidence based on pharmacological and genetic studies suggests that
      retinoid signaling plays an important role in developmental control of striatal
      neurons. In the present report, we screened for genes that might be regulated by
      retinoids in the developing striatum. We cultured tissue explants from the
      lateral ganglionic eminence (striatal primordium), and for regional comparison,
      its adjacent structures of the cerebral cortex and the medial ganglionic eminence
      in embryonic day 15 rat telencephalon. Using the ribonuclease protection assay,
      we found that both all-trans retinoic acid and 9-cis retinoic acid significantly
      up-regulated dopamine D1 receptor, heterotrimeric G protein olfactory, adenylyl
      cyclase type V and dopamine- and cyclic adenosine 3':5'-monophosphate-regulated
      phosphoprotein mRNAs in the lateral ganglionic eminence culture. By contrast,
      neither all-trans retinoic acid nor 9-cis retinoic acid significantly altered D1
      receptor, heterotrimeric G protein olfactory, adenylyl cyclase type V and
      dopamine- and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein mRNAs
      in the cortical and the medial ganglionic eminence cultures except that D1
      receptor mRNA was dramatically induced in the medial ganglionic eminence by
      retinoic acid treatments. To test whether the induction of multiple dopamine
      signaling molecules in the lateral ganglionic eminence was due to a general
      enhancement of neuronal differentiation by retinoic acid, we assayed the effects
      of retinoic acid on other differentiation markers, including glutamate
      decarboxylase 65, NR1 subunit of glutamate NMDA receptor and microtubule
      associated protein-2. None of these genes were significantly altered by retinoic
      acid treatments in the lateral ganglionic eminence culture, indicating the
      specificity of gene regulation by retinoic acid signaling. As D1 receptor,
      heterotrimeric G protein olfactory, adenylyl cyclase type V and dopamine- and
      cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein are important
      molecules involved in propagation of striatal dopamine neurotransmission, our
      study raises the hypothesis that retinoid signaling may coordinately activate the
      transcriptional program that is associated with the dopamine signaling pathway in
      developing striatal neurons. Such coordinate regulation by retinoids may be part
      of the mechanisms by which the complex yet highly organized neurochemical
      constituents of the striatum are established during development.

PMID- 15939543
TI  - Involvement of the bed nucleus of the stria terminalis activated by the central
      nucleus of the amygdala in the negative affective component of morphine
      withdrawal in rats.
AB  - The central nucleus of the amygdala (Ce) and the bed nucleus of the stria
      terminalis (BST) are key structures of the extended amygdala, which is suggested
      to be involved in drug addiction and reward. We have previously reported that the
      Ce plays a crucial role in the negative affective component of morphine
      withdrawal. In the present study, we examined the involvement of the neural
      pathway between the Ce and the BST in the negative affective component of
      morphine withdrawal in rats. Rats were rendered morphine dependent by s.c.
      implantation of a 75-mg morphine pellet for 3 days, and morphine withdrawal was
      precipitated by an i.p. injection of naloxone (0.3 mg/kg). In the place
      conditioning paradigm, discrete bilateral excitotoxic lesions of the Ce or the
      BST significantly reduced naloxone-precipitated morphine withdrawal-induced
      conditioned place aversion. On the other hand, they had little effect on morphine
      withdrawal-induced somatic signs. In an immunohistochemical study for c-Fos
      protein, naloxone-precipitated morphine withdrawal dramatically induced c-Fos
      immunoreactive neurons in the capsular part of the Ce, and the lateral and medial
      divisions of the BST. Bilateral excitotoxic lesion of the Ce reduced the number
      of morphine withdrawal-induced c-Fos-immunoreactive neurons in the lateral and
      medial BST, with significant decreases in the posterior, ventral and
      juxtacapsular parts of lateral division, and anterior part of the medial
      division, but not in the ventral part of the medial division of the BST. On the
      other hand, bilateral excitotoxic lesion of the BST had no effect on such c-Fos
      induction within the capsular part, nor the ventral and medial divisions of the
      Ce. These results suggest that activation of the BST mediated through the neural
      pathway from the Ce contributes to the negative affective component of morphine
      withdrawal.

PMID- 15939544
TI  - Effect of N-methyl-d-aspartate receptor blockade on neuronal plasticity and
      gastrointestinal transit delay induced by ischemia/reperfusion in rats.
AB  - Intestinal ischemia impairs gastrointestinal motility. The aims of this study
      were to investigate the effect of intestinal ischemia on gastrointestinal transit
      and on the expression of enteric transmitters in the rat, and whether the
      glutamate N-methyl-d-aspartate receptors influence these effects. Ischemia (1 h),
      induced by occluding the superior mesenteric artery, was followed by 0 or 24 h of
      reperfusion. Normal and sham-operated rats served as controls. Serosal blood flow
      was measured with laser Doppler flow meter. Gastrointestinal transit was measured
      as time of appearance of a marker in fecal pellets. Immunohistochemistry was used
      to evaluate the number of neurons immunoreactive for neuronal nitric oxide
      synthase (NOS) or vasoactive intestinal polypeptide and the density of substance
      P immunoreactive fibers in the myenteric plexus. The N-methyl-d-aspartate
      receptors antagonist, (+)-5-methyl-10,11-dihydro-5HT-[a,b] cyclohepten-5,10-imine
      (MK-801) (1 mg/kg i.v.) or the NOS inhibitor, N-nitro-l-arginine (10 mg/kg i.v.)
      was administered prior to ischemia. Serosal blood flow was decreased by 70%
      during ischemia, but it was not altered in sham-operated rats. Gastrointestinal
      transit was significantly prolonged in ischemic/reperfused rats compared with
      controls. There was a significant increase in the number of vasoactive intestinal
      polypeptide and neuronal nitric oxide synthase immunoreactive neurons, and a
      marked decrease of substance P immunoreactive fibers in ischemia followed by 24 h
      of reperfusion animals compared with controls. These alterations were not
      observed in ischemia without reperfusion. A significant delay of gastrointestinal
      transit and increase of vasoactive intestinal polypeptide neurons were also
      observed in sham-operated rats. The changes in transmitter expression and
      gastrointestinal transit in ischemic/reperfused rats were prevented by pre
      treatment with the NOS inhibitor, N-nitro-l-arginine or the N-methyl-d-aspartate
      receptors antagonist, MK-801. This study suggests an involvement of the
      glutamatergic system and its interaction with nitric oxide in intestinal
      ischemia/reperfusion. Ischemia/reperfusion might induce local release of
      glutamate that activates N-methyl-d-aspartate receptors leading to increased
      production of nitric oxide and adaptive changes in enteric transmitters that
      might contribute to gastrointestinal dysmotility.

PMID- 15939545
TI  - Effects of minocycline and tetracycline on retinal ganglion cell survival after
      axotomy.
AB  - In the present study, we compared the in vivo neuroprotective efficacy of
      intraperitoneally administered tetracycline and minocycline to enhance the
      survival of retinal ganglion cells (RGCs) following unilateral axotomy of the
      adult rat optic nerve. We also examined the effects of the tetracycline drugs on
      the activation of retinal microglia. RGCs in retinal whole-mounts were visualized
      by retrograde labeling with fluorogold. The presence of activated microglia was
      confirmed immunohistochemically using OX-42 monoclonal antibodies. Optic nerve
      axotomy produced RGC death and increased activation of microglia. No significant
      RGC loss was seen prior to 5 days and approximately 50% and 80-90% cell loss
      occurred at 7 and 14 days, respectively. Examination of the effects of
      tetracycline and minocycline on RGC survival at 7 days post-axotomy, revealed
      increased numbers of RGCs in minocycline-treated animals (75% of non-axotomized
      control) compared with vehicle-only (52% of control) and tetracycline-treated
      (58% of control) animals. The densities of RGCs (RGCs/mm2+/-S.D.) for control,
      vehicle-, tetracycline- and minocycline-treated axotomized animals were 1996+/
      81, 1029+/-186, 1158+/-190 and 1497+/-312, respectively. The neuroprotective
      effect of minocycline seen at 7 days was transient, since RGCs present in
      minocycline-treated animals at 14 days post-axotomy (281+/-43, 14% of control)
      were not significantly different to vehicle-treated animals (225+/-47, 11% of
      control). OX-42 staining of activated retinal microglia was reduced in
      tetracycline- and minocycline-treated axotomized animals compared with axotomized
      animals receiving vehicle-only. These results demonstrate that systemic
      administration of the second-generation tetracycline derivative, minocycline,
      delays the death of axotomized RGCs by a mechanism that may be associated with
      inhibition of microglia activation. The neuroprotective efficacy of minocycline
      following optic nerve axotomy was superior to that of tetracycline.

PMID- 15939546
TI  - Expanding stress theory: prolonged activation and perseverative cognition.
AB  - Several theories of the stress-disease link have now incorporated prolonged
      activation. This article argues that these theories still lack an important
      element, that is, the cognitive nature of the mechanism that causes stress
      responses to be sustained. The perception of stress and the initial response to
      it do not automatically lead to prolonged activation. The active cognitive
      representations of stressors need to be prolonged in order to extend their
      physiological concomitants. We call this mediating process perseverative
      cognition, and it is manifested in phenomena such as worry, rumination, and
      anticipatory stress. We summarize evidence suggesting that these phenomena are
      indeed associated with physiological activation, including cardiovascular,
      endocrinological and immunological parameters. This evidence is still far from
      sufficient, due to the many methodological insufficiencies in the studies
      involved. Nevertheless, it makes clear that cognitive phenomena characterized by
      perseverative cognition may be likely candidates to mediate the effects of stress
      sources on somatic disease. We also argue that there is a dearth of evidence
      supporting the role of prolonged activation. There are a limited number of
      studies demonstrating prolonged activity related to stressors and emotional
      episodes, and their methodologies often do not allow unambiguous conclusions.
      Even more important, the crucial assumption that prolonged activation actually
      leads to pathogenic states and disease has received hardly any attention yet and
      therefore is still largely unsupported. There are only a few studies that showed
      that anticipatory responses and slow recovery from stress predicted disease
      states.

PMID- 15939547
TI  - Volume and hormonal effects for acute side effects of rectum and bladder during
      conformal radiotherapy for prostate cancer.
AB  - PURPOSE: To identify dosimetric variables predictive of acute gastrointestinal
      (GI) and genitourinary (GU) toxicity and to determine whether hormonal therapy
      (HT) is independently associated with acute GI and GU toxicity in prostate cancer
      patients treated with conformal radiotherapy (RT). METHODS AND MATERIALS: This
      analysis was performed on 336 patients participating in a multicenter (four
      hospitals) randomized trial comparing 68 Gy and 78 Gy. The clinical target volume
      consisted of the prostate with or without the seminal vesicles, depending on the
      risk of seminal vesicle involvement. The margin from the clinical target volume
      to the planning target volume was 1 cm. For these patients, the treatment plan
      for a total dose of 68 Gy was used, because nearly all toxicity appeared before
      the onset of the 10-Gy boost. Acute toxicity (<120 days) was scored according to
      the Radiation Therapy Oncology Group criteria. The dosimetric parameters were
      obtained from the relative and absolute dose-volume/surface histograms derived
      from the rectal wall (rectal wall volume receiving > or =5-65 Gy) and the bladder
      surface (bladder surface receiving > or =5-65 Gy). Additionally, relative and
      absolute dose-length histograms of the rectum were created, and the lengths of
      rectum receiving more than a certain dose over the whole circumference (rectal
      length receiving > or =5-65 Gy) were computed. The clinical variables taken into
      account for GI toxicity were neoadjuvant HT, hospital, and dose-volume group; for
      GU toxicity, the variables pretreatment GU symptoms, neoadjuvant HT, and
      transurethral resection of the prostate were analyzed. The variable neoadjuvant
      HT was divided into three categories: no HT, short-term neoadjuvant HT (started <
      or =3 months before RT), and long-term neoadjuvant HT (started >3 months before
      RT). RESULTS: Acute GI toxicity Grade 2 or worse was seen in 46% of the patients.
      Patients with long-term neoadjuvant HT experienced less Grade 2 or worse toxicity
      (27%) compared with those receiving short-term neoadjuvant HT (50%) and no HT
      (50%). The volumes of the prostate and seminal vesicles were significantly
      smaller in both groups receiving neoadjuvant HT compared with those receiving no
      HT. In multivariate logistic regression analysis, including the two statistically
      significant clinical variables neoadjuvant HT and hospital, a volume effect was
      found for the relative, as well as absolute, rectal wall volumes exposed to
      intermediate and high doses. Of all the length parameters, the relative rectal
      length irradiated to doses of > or =5 Gy and > or =30 Gy and absolute lengths
      receiving > or =5-15 and 30 Gy were significant. Acute GU toxicity Grade 2 or
      worse was reported in 56% of cases. For patients with pretreatment GU symptoms,
      the rate was 93%. The use of short-term and long-term neoadjuvant HT resulted in
      more GU toxicity (73% and 71%) compared with no HT (50%). In multivariate
      analysis, containing the variables pretreatment symptoms and neoadjuvant HT, only
      the absolute dose-surface histogram parameters (absolute surface irradiated to >
      or =40, 45, and 65 Gy) were significantly associated with acute GU toxicity.
      CONCLUSION: A volume effect was found for acute GI toxicity for relative, as well
      as absolute, volumes. With regard to acute GU toxicity, an area effect was found,
      but only for absolute dose-surface histogram parameters. Neoadjuvant HT appeared
      to be an independent prognostic factor for acute toxicity, resulting in less
      acute GI toxicity, but more acute GU toxicity. The presence of pretreatment GU
      symptoms was the most important prognostic factor for GU symptoms during RT.

PMID- 15939548
TI  - Correlation of dosimetric factors and radiation pneumonitis for non-small-cell
      lung cancer patients in a recently completed dose escalation study.
AB  - PURPOSE: To determine dosimetric factors for lung, lung subregions, and heart
      that correlate with radiation pneumonitis (Radiation Therapy Oncology Group Grade
      3 or more) in the 78 evaluable patients from a Phase I dose escalation study
      (1991-2003) of three-dimensional conformal radiation therapy (3D-CRT) of non
      small-cell lung cancer. METHODS AND MATERIALS: There were 10 > or = Grade 3
      pneumonitis cases within 6 months after treatment. Dose-volume factors analyzed
      for univariate correlation with > or = Grade 3 pneumonitis were mean dose (MD),
      effective uniform dose (d(eff)), normal tissue complication probability (NTCP),
      parallel model f(dam) and V(D) for 5 < or = D < or = 60 Gy for whole,
      ipsilateral, contralateral, upper and lower halves of the lungs and heart D05,
      and mean and maximum doses. RESULTS: The most significant variables (0.005 < p <
      0.006) were ipsilateral lung V(D) for D < 20 Gy. Also significant (p < 0.05) for
      ipsilateral lung were V(D) for D < 50 Gy, MD, f(dam) and d(eff); for total lung
      V(D) (D < 50 Gy), MD, f(dam), d(eff) and NTCP; for lower lung V(D) (D < 60 Gy),
      MD, f(dam) and d(eff). All variables for upper and contralateral lung were
      insignificant, as were heart variables. CONCLUSIONS: Previously reported
      correlations between severe pneumonitis and whole lung V13 and with other dose
      volume factors of total lung and lower lung are confirmed. The most significant
      correlations were for (V05-V13) in ipsilateral lung.

PMID- 15939549
TI  - Spinal reirradiation after short-course RT for metastatic spinal cord
      compression.
AB  - PURPOSE: To investigate the feasibility and effectiveness of reirradiation (re
      RT) for in-field recurrence of metastatic spinal cord compression after primary
      RT with 1 x 8 Gy or 5 x 4 Gy. METHODS AND MATERIALS: A total of 62 patients,
      treated with 1 x 8 Gy (n = 34) or 5 x 4 Gy (n = 28) between January 1995 and
      August 2003, received re-RT for in-field recurrence of metastatic spinal cord
      compression. The median time to recurrence was 6 months (range, 2-40 months). Re
      RT was performed with 1 x 8 Gy (after 1 x 8 Gy or 5 x 4 Gy, n = 34), 5 x 3 Gy
      (after 1 x 8 Gy or 5 x 4 Gy, n = 15), or 5 x 4 Gy (after 1 x 8 Gy, n = 13). The
      cumulative biologically effective dose (primary RT plus re-RT) was 80-100 Gy2.
      The median follow-up after re-RT was 8 months (range, 2-42 months). Motor
      function was evaluated up to 6 months after re-RT. RESULTS: After re-RT, 25
      patients (40%) showed improvement of motor function, 28 (45%) had no change, and
      9 (15%) had deterioration. Of the 16 previously nonambulatory patients, 6 (38%)
      regained the ability to walk. No second in-field recurrence in the same spinal
      region was observed after re-RT. The outcome was not significantly influenced by
      the radiation schedule. Radiation myelopathy was not observed. CONCLUSIONS:
      Spinal re-RT with 1 x 8 Gy, 5 x 3 Gy, or 5 x 4 Gy for in-field recurrence of
      metastatic spinal cord compression appears safe and effective. Myelopathy seems
      unlikely, if the cumulative biologically effective dose is < or = 100 Gy2.

PMID- 15939550
TI  - Duration, response, and location: the influence of upcoming 32% sucrose on rats'
      licking or lever pressing for 1% liquid sucrose.
AB  - The present study investigated whether rats' rates of licking or pressing a lever
      for 1% liquid sucrose delivered by a continuous reinforcement schedule would
      decrease (contrast) or increase (induction) when the upcoming period would allow
      access to 32% sucrose and whether such changes would be influenced by how long
      each substance was available. In Experiment 1, different groups of rats licked a
      spout or pressed a lever for 1% sucrose in the first half of the session and, in
      different conditions, for 1% or 32% sucrose in the second half. Across
      conditions, halves of the session were 3, 6, 12, or 24 min long. Upcoming 32%
      sucrose significantly decreased rates of licking at each duration whereas it
      increased rates of lever pressing except when access duration was 3 min.
      Experiment 2 replicated Experiment 1 with the exception that rats that licked did
      so from the same spout in both halves of the session and rats that pressed a
      lever collected the sucrose reinforcers in the different halves at different
      locations. In these procedures, upcoming 32% sucrose significantly increased
      rates of licking. Significant, but small, increases in rates of lever pressing
      were still observed. The present results suggest that continuous reinforcement or
      duration of access to sucrose are not primary determinants of whether contrast or
      induction is observed. Rather, they suggest that the type of behavior (licking
      versus pressing a lever) and the location at which the substances are collected
      and consumed play a large role in which effect occurs.

PMID- 15939551
TI  - Reinstatement of a food-maintained operant produced by compounding discriminative
      stimuli.
AB  - After a tone and a light were established as discriminative stimuli for food
      reinforced responding in rats, presenting these stimuli simultaneously produced
      over three times as many responses as either the tone or light alone. Following
      this stimulus compounding test, responses during the tone and during the light
      were not reinforced (extinction) for 20 sessions, essentially eliminating
      responding. On stimulus compounding tests administered after the 10th and 20th
      extinction sessions, tone-plus-light continued to produce significantly more
      responding than the tone or light alone. The compound even produced responses
      when the individual stimuli no longer did. These results suggest that the
      simultaneous presentation of multiple extinguished discriminative stimuli may
      also contribute to the reinstatement of other positively-reinforced behaviors,
      such as drug taking.

PMID- 15939552
TI  - Detection of temporal patterns in dog-human interaction.
AB  - A new time structure model and pattern detection procedures developed by
      (Magnusson, M.S., 1996. Hidden real-time patterns in intra- and inter-individual
      behaviour description and detection. Eur. J. Psychol. Assess. 12, 112-123;
      Magnusson, M.S., 2000. Discovering hidden time patterns in behaviour: T-patterns
      and their detection. Behav. Res. Methods, Instrum. Comput. 32, 93-110) enables us
      to detect complex temporal patterns in behaviour. This method has been used
      successfully in studying human and neuronal interactions (Anolli, L., Duncan, S.
      Magnusson, M.S., Riva G. (Eds.), 2005. The Hidden Structure of Interaction, IOS
      Press, Amsterdam). We assume that similarly to interactions between humans,
      cooperative and communicative interaction between dogs and humans also consist of
      patterns in time. We coded and analyzed a cooperative situation when the owner
      instructs the dog to help build a tower and complete the task. In this situation,
      a cooperative interaction developed spontaneously, and occurrences of hidden time
      patterns in behaviour can be expected. We have found such complex temporal
      patterns (T-patterns) in each pair during the task that cannot be detected by
      "standard" behaviour analysis. During cooperative interactions the dogs' and
      humans' behaviour becomes organized into interactive temporal patterns and that
      dog-human interaction is much more regular than yet has been thought. We have
      found that communicative behaviour units and action units can be detected in the
      same T-pattern during cooperative interactions. Comparing the T-patterns detected
      in the dog-human dyads, we have found a typical sequence emerging during the
      task, which was the outline of the successfully completed task. Such temporal
      patterns were conspicuously missing from the "randomized data" that gives
      additional support to the claim that interactive T-patterns do not occur by
      chance or arbitrarily but play a functional role during the task.

PMID- 15939553
TI  - Characterization of the origin recognition complex (ORC) from a higher plant,
      rice (Oryza sativa L.).
AB  - The origin recognition complex (ORC) protein plays a critical role in DNA
      replication through binding to sites (origins) where replication commences. The
      protein is composed of six subunits (ORC1 to 6) in animals and yeasts. Our
      knowledge of the ORC protein in plants is, however, much less complete. We have
      performed cDNA cloning and characterization of ORC subunits in rice (Oryza sativa
      L. cv. Nipponbare) in order to facilitate study of plant DNA replication
      mechanisms. Our previous report provided a description of a gene, ORC1 (OsORC1),
      that encodes one of the protein subunits. The present report extends this initial
      analysis to include the genes that encode four other rice ORC subunits, OsORC2,
      3, 4 and 5. Northern hybridization analyses demonstrated the presence of abundant
      transcripts for all OsORC subunits in shoot apical meristems (SAM) and cultured
      cells, but not in mature leaves. Interestingly, only OsORC5 showed high levels of
      expression in organs in which cell proliferation is not active, such as flag
      leaves, the ears and the non-tip roots. The pattern of expression of OsORC2 also
      differed from other OsORC subunits. When cell proliferation was temporarily
      halted for 6-10 days by removal of sucrose from the growth medium, expression of
      OsORC1, OsORC3, OsORC4 and OsORC5 was substantially reduced. However, the level
      of expression of OsORC2 remained constant. We suggest from these results that
      expression of OsORC1, 3, 4 and 5 are correlated with cell proliferation, but the
      expression of OsORC2 is not.

PMID- 15939555
TI  - Antibacterial effect of Cu2+-exchanged montmorillonite on Aeromonas hydrophila
      and discussion on its mechanism.
AB  - Montmorillonite (MMT) and its Cu2+-exchanged montmorillonite (Cu-MMT) were used
      to study the antibacterial activity on Aeromonas hydrophila. The results
      indicated that MMT had no antibacterial activity. The minimum inhibitory
      concentration (MIC) and bactericidal concentration (MBC) of Cu-MMT on A.
      hydrophila are found to be 150 and 600 mg/L, respectively. The continuance of the
      antibacterial activity of Cu-MMT was much longer than copper sulfate. In order to
      reveal the mechanism of the antibacterial activity of Cu-MMT, the Cu release from
      Cu-MMT in tryptic soy broth (TSB) was investigated. In the first 2 h, Cu
      concentration in the supernatant reaches saturated value, about 1.22-2.27% of the
      overall Cu in Cu-MMT suspended in the medium. The washed Cu-MMT in TSB for 24 h
      retained their full antibacterial activity; whereas, the supernatants from the
      washed pellets showed very little antibacterial activity. These findings
      suggested that the antibacterial activity of Cu-MMT was mainly localized on the
      clay surface, and not due to the release of Cu2+ into solution. The excessive
      positive charge of Cu-MMT would make Cu-MMT attract A. hydrophila with negatively
      charged cellular wall. In this case, the copper cation would act directly on the
      bacteria adsorbed on the surface of Cu-MMT, instead of into the medium. The
      mechanism for the antibacterial activity of Cu-MMT may involve the enhanced
      affinity of Cu-MMT for A. hydrophila and the antibacterial activity of Cu2+.

PMID- 15939554
TI  - Genomic structure and functional characterization of the promoter region of human
      IkappaB kinase-related kinase IKKi/IKKvarepsilon gene.
AB  - The inducible IkappaB kinase (IKKi/IKKepsilon) is a recently described serine
      threonine kinase that activates the transcription factors NFkappaB, interferon
      regulatory factor-3 (IRF3) and CCAAA/enhancer-binding protein (C/EBPdelta).
      Several inflammatory agents have been shown to induce the expression of the IKKi
      gene in macrophages and other cell types but the mechanism is unknown. We have
      found that the IKKi expression was constitutive in human chondrocytes from OA
      cartilage and a human chondrocytic cell line C28/I2 but was up-regulated by the
      inflammatory cytokines TNFalpha or IL-1betain an NFkappaB-dependent manner. To
      understand the constitutive and inducible expression of the IKKi gene we
      localized the transcription start site (TSS), cloned and sequenced a 2 kb genomic
      DNA fragment 5' of the TSS and characterized the putative promoter region (PPR),
      and identified the motifs therein that are required for basal and cytokine
      induced IKKi gene promoter activity. We found that IKKi core promoter was TATA
      less and by using PCR generated deletion mutants of the PPR we found that the cis
      elements responsible for basal transcriptional activity were located between -51
      and -100 bp upstream of the TSS while the cytokine response elements were located
      distally between -501 and -1000 bp upstream of the TSS. The DNA region containing
      the cytokine response elements had two kappaB sites as the most relevant
      regulatory motifs. The results of site-directed mutagenesis revealed that the
      kappaB site located between -833 and -847 bp upstream of the TSS was biologically
      functional and required for cytokine-induced IKKi promoter activity in human
      chondrocytes and HeLa cells. The silence of the other kappaB site (-816/-802) was
      positional, rather than sequence-specific. Over-expression of NFkappaB p65 mimics
      the TNFalpha-induced activation of the IKKi promoter. Also the gel shift assay
      suggested that NFkappaB p65 is responsible for activation of the IKKi promoter.
      These data for the first time characterize the promoter region and provide
      further insights into the transcriptional regulation of IKKi in human
      chondrocytes and other cell types.

PMID- 15939556
TI  - Comparison of milk-ELISA and serum-ELISA for the diagnosis of Brucella melitensis
      infection in sheep.
AB  - Milk and blood samples from 704 lactating ewes were examined for the diagnosis of
      Brucella melitensis infection by milk-ELISA, serum-ELISA, RBPT, SAT and culture
      of milk. Of these ewes, 209 were from brucellosis free sheep flock, 443 from
      brucellosis infected sheep flock and 52 were from private sheep flocks of which
      status for brucellosis was not known. All the 209 ewes belonging to uninfected
      sheep flock were found negative in all the tests and of the remaining 495 ewes
      105 were positive in serum-ELISA, 103 in milk-ELISA, 92 in RBPT, 85 in SAT, and
      B. melitensis biovar-1 was isolated from the milk of 29 ewes. Of the 105 serum
      ELISA positive ewes, 99 were positive and 6 were negative in milk-ELISA, whereas
      of the 103 milk-ELISA positive ewes, 4 were negative in serum-ELISA. All
      together, 99 ewes were positive and 386 were negative in both the assays while 10
      ewes yielded variable results. The specificity of milk-ELISA in brucellosis free
      flock was 100% and sensitivity and positive predictive value were 96.11% and
      94.28%, respectively, in infected flocks. The Brucella antibody levels in milk
      and serum samples as determined by milk-ELISA and serum-ELISA were correlated
      significantly. The milk-ELISA for brucellosis appears to be an attractive
      alternative of serum-ELISA particularly in the lactating ewes.

PMID- 15939557
TI  - Feline herpesvirus type-1 transcription is associated with increased nasal
      cytokine gene transcription in cats.
AB  - The etiopathogenesis of chronic nasal discharge in the cat is poorly understood.
      The objective of this study was to investigate alterations in transcription of
      genes for cytokines and chemokines in association with feline herpesvirus-1 (FHV
      1) mRNA transcription. Nasal samples from 21 cats were submitted for FHV-1 virus
      isolation (VI), traditional endpoint polymerase chain reaction (PCR) detection of
      FHV-1 DNA, and quantitative real-time TaqMan PCR analysis of cytokines and
      chemokines (interleukin [IL]-4, IL-5, IL-6, IL-10, IL-12p40, IL-16, IL-18,
      interferon [IFN]-gamma, tumor necrosis factor [TNF]-alpha, and regulated on
      activation normal T cell expressed and secreted protein [RANTES]) and of FHV-1
      mRNA and DNA. Co-infection with feline calicivirus or Chlamydophila spp. was
      excluded in all cats. Gene transcription in nasal samples from four specific
      pathogen free (SPF) cats served as the calibrator for cytokines. FHV-1 was
      detected by VI in 14 of 21 samples, by traditional PCR in 18 of 21 samples, and
      by quantitative PCR in 13 (mRNA+) and 18 (DNA+) samples. Nasal samples from cats
      positive for FHV-1 mRNA displayed significantly increased transcription of IL-6,
      IL-10, IL-12p40, IL-18, IFN-gamma, TNF-alpha, and RANTES (P<0.05) in comparison
      to samples from cats negative for FHV-1 mRNA. The cycle threshold for FHV-1 DNA
      was significantly higher in cats with detectable FHV-1 mRNA (P<0.05). Increased
      transcription of cytokines/chemokines in cats with detectable mRNA for FHV-1
      suggests a role for FHV-1 in nasal inflammation.

PMID- 15939558
TI  - Monte Carlo simulation of classical swine fever epidemics and control. II.
      Validation of the model.
AB  - A stochastic and spatial simulation model was developed to simulate the spread of
      classical swine fever virus among herds in a certain area. A model is a
      simplification of a real system. The mechanisms and parameters are often not
      exactly known. Validation is necessary to gain insight into model behaviour and
      to identify risk factors with great impact on the response variables. Several
      risk factors such as incubation period, number of daily farm contacts,
      probability of detection, probability of infection after contact, probability of
      local spread and time from infection to infectivity were considered in the model
      as probability distributions in order to take the stochastic component of disease
      dynamics into account. In order to estimate the effects of the risk factors on
      the response variables mean size and duration of epidemics, a sensitivity
      analysis was performed. A fractional factorial design with two-level factors (2(7
      2) design) was developed to gain the maximum strength with minimum demand on the
      calculating capacity. The main factors were unconfounded with any other main
      factor and also unconfounded with two-factor interactions. Apart from the time
      from infection to infectivity, all risk factors had a significant effect on the
      mean size and duration of epidemics (p<0.05). Eight two-factor interactions had a
      significant influence as well (p<0.05). Mainly, two-factor interactions with
      probability of detection were significant thus emphasising the impact of a rapid
      detection of outbreaks. The reaction of the simulation responses to changing of
      the parameter values was consistent with the expected reaction.

PMID- 15939559
TI  - Timing of emergence of ovulatory follicles in polyovulatory goats.
AB  - The current study characterized the timing of emergence of ovulatory follicles
      during the follicular phase of the estrous cycle in polyovulatory does and
      assessed whether selection may influence ovulation rate through differences in
      ovarian follicular dynamics, by characterizing preovulatory follicular emergence
      and growth in two ecotypes of Neuquen-Criollo Argentinean goats (Short-Hair, n=11
      and Long-Hair, n=9). During the breeding season, the time of estrus was
      synchronized in all does with two doses of a prostaglandin analogue. Ovarian
      laparoscopies were performed on days 17 and 19 after the induced estrus (day 0)
      and 7-15 h after the beginning of the subsequent estrus. Results indicate that
      both ecotypes of goats have common features in the ovarian follicular population
      and in the patterns of preovulatory follicular enlargement. In all the goats,
      most of the preovulatory follicles arose from the pool of follicles present in
      the ovary between days 17 and 19 of the estrous cycle. These follicles were all
      larger than 2mm at emergence, being the largest growing follicle present in the
      ovaries on days 17 and 19 in 56.5 and 78.6% of the does, respectively. The
      appearance of new follicles remained unaffected, while the mean number of small
      growing follicles decreased (P<0.05) during the follicular phase, indicating that
      preovulatory follicles do not suppress the emergence of new follicles but inhibit
      the growth of small follicles. A separate analysis of single and double ovulating
      does showed that 75% of the second ovulatory follicles in polyovulatory goats was
      present on the ovarian surface between days 17 and 19 of the estrous cycle, but
      appeared later in the other 25% of the estrous cycles. These findings support the
      hypothesis that follicular dominance effects are exerted during the preovulatory
      period, when the growth of follicles other than the ovulatory is inhibited, and
      that increases in ovulation rate in small ruminants are related to a reduced
      incidence of follicular atresia and an extended period of ovulatory follicle
      recruitment.

PMID- 15939560
TI  - Postmenopausal hormone therapy and mammographic breast density.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of different types
      of hormone replacement therapy (HRT) on mammographic density. MATERIALS AND
      METHODS: In a prospective 1-year study, 103 postmenopausal women were randomized
      to receive tibolone 2.5 mg/die, continuous conjugated equine estrogens 0.625
      mg/die plus medroxyprogesterone acetate (MPA) 5mg/die or placebo. Mammograms were
      performed at baseline and after 12 months of treatment. Mammographic density was
      quantified according to the Wolfe classification. RESULTS: After 12 months of HRT
      16 of the 35 patients (45.1%) receiving continuous combined hormonal therapy
      showed an increase of breast density change in the Wolfe classification. After
      treatment with tibolone, an up grading in breast density, according to Wolfe's
      classification, was found in 2 of the 43 patients (2.3%). No changes were
      recorded in the 25 patients of the control group. The difference between the
      group treated with continuous combined hormonal therapy and the control group was
      highly significant (p<0.001). The difference in breast density between patients
      in treatment with tibolone and the control group was not statistically
      significant (p=0.34). DISCUSSION: Continuous combination HRT may be more commonly
      associated with an increase of mammography density than tibolone treatment.

PMID- 15939561
TI  - The diffusion of latex nanospheres and the effective (microscopic) viscosity of
      HPMC gels.
AB  - Dynamic light scattering (DLS) has been used to measure the diffusion
      coefficients of 108+/-7 (+/-S.D.) and 495+/-23 nm positively charged amino latex
      nanospheres (ALNs) and negatively charged carboxyl latex nanospheres (CLNs) (48+/
      7, 91+/-9.8 and 483+/-10 nm) in three different media, water, glycerol aqueous
      solutions and hydroxypropyl methylcellulose (HPMC) gels. The translational
      diffusion coefficients (D) of these latex spheres in water were found to be 13.00
      (+/-0.12), 5.11 (+/-0.06), 0.89 (+/-0.01) microm2/s for 48, 91 and 483 nm CLN,
      and 3.26 (+/-0.01) and 0.88 (+/-0.03) microm2/s for 108 and 495 nm ALN,
      respectively. In Newtonian glycerol aqueous solutions as anticipated the
      diffusion could be predicted by the Stokes-Einstein relationship over a range of
      system viscosities. In HPMC gels the results show the deviation of the diffusion
      coefficient from the Stokes-Einstein equation when the viscosity of the medium is
      increased. In addition, there was an increase in the polydispersity index (PI)
      from 0.217 to 0.928 with 108 nm ALN on increasing HPMC concentrations from 0.2%
      to 0.8% (w/v), which implied an interaction between the positively charged
      nanospheres and the gel. From the D values, the "effective" or "microscopic"
      viscosities of the HPMC medium were calculated, and ranged from 0.899 to 0.925
      mPa s.

PMID- 15939562
TI  - Stability indicating RP-HPLC method for simultaneous determination of amlodipine
      and benazepril hydrochloride from their combination drug product.
AB  - A stability indicating reversed-phase HPLC method has been developed and
      subsequently validated for simultaneous estimation of amlodipine (AM) present as
      amlodipine besylate (AB), and benazepril hydrochloride (BH) from their
      combination product. The proposed RP-HPLC method utilizes a Zorbax SB C18, 5
      microm, 250 mm x 4.6 mm i.d. column, mobile phase consisting of phosphate buffer
      and acetonitrile in the proportion of 65:35 (v/v) with apparent pH adjusted to
      7.0, and UV detection at 240 nm using a photodiode array detector. AB, BH, and
      their combination drug product were exposed to thermal, photolytic, hydrolytic,
      and oxidative stress conditions, and the stressed samples were analysed by the
      proposed method. Peak homogeneity data of AM and BH peaks obtained using
      photodiode array detector, in the stressed sample chromatograms, demonstrated the
      specificity of the method for their estimation in presence of degradants. The
      described method was linear over a range of 6-14 microg/ml for AM and 12-28
      microg/ml for BH. The mean recoveries were 99.91 and 100.53% for AM and BH,
      respectively. F-test and t-test at 95% confidence level were used to check the
      intermediate precision data obtained under different experimental setups; the
      calculated value was found to be less than critical value.

PMID- 15939563
TI  - Evaluation of the stability of chlortetracycline in granular premixes by
      monitoring its conversion into degradation products.
AB  - A methodology for the evaluation of the stability of chlortetracycline (CTC) in
      granular premixes is described. This methodology is based on the monitoring of
      the conversion of CTC into its degradation products by an improved gradient
      liquid chromatography (LC) method, based on one previously described by our
      laboratory. Sample preparation involves the extraction of CTC and its degradation
      products prior to LC analysis, using acidified methanol as extraction solvent.
      The gradient elution LC method proved to be very sensitive, especially towards
      the late eluting anhydro derivatives. The use of a Hypersil C8 BDS, 5 microm, 250
      mm x 4.6 mm i.d. column is recommended since this column allowed a complete
      separation of the different impurities from each other and from the main
      component CTC. The applicability of this approach was demonstrated by the
      analysis of stability samples.

PMID- 15939564
TI  - Pharmacokinetic study of trimebutine maleate in rabbit blood using in vivo
      microdialysis coupled to capillary electrophoresis.
AB  - In vivo microdialysis was used together with capillary electrophoresis (CE) to
      monitor the concentration of trimebutine maleate (TM) in rabbit blood. Dialysis
      probe was perfused at 3 microl/min resulting in relative recovery of 26.6+/-3.1%
      (n=3). After a one step sample preparation the samples were injected directly
      into the capillary. TM was detected on-column using UV detector at 214 nm.
      Separation of TM from other components in the dialysate was achieved within 15
      min. Evaluation was based on the relative collected peak height (TM/IS). The
      response for TM in the blood dialysate was linear over the range of 0.5-100
      microg/ml. The detection limit of TM in the blood dialysate was 0.1 microg/ml
      (S/N=3). This method has been successfully applied to the pharmacokinetic study
      of trimebutine maleate in rabbit blood following oral administration of 200
      mg/kg. It provides a fast and simple technique for the pharmacokinetic study of
      TM in vivo.

PMID- 15939565
TI  - An assessment of calibration and performance of the microdialysis system.
AB  - To improve the reliability of microdialysis measurements of tissue concentrations
      of metabolic substances, this study was designed to test both the performance and
      the internal validity of the microdialysis methods in the hands of our research
      group. The stability of the CMA 600 analyser was tested with a known glucose
      solution in 72 standard microvials and in 48 plastic vials. To evaluate if
      variation in sampling time makes any difference in sample concentration
      (recovery), sampling times of 10, 20 and 30 min were compared in vitro with a
      constant flow rate of 1 microl/min. For testing of sampling times at different
      flow rates, an in vitro study was performed in which a constant sample volume of
      10 microl was obtained. With the no net flux method, the actual concentration of
      glucose and urea in subcutaneous tissue was measured. The CMA 600 glucose
      analysis function was accurate and stable with a coefficient of variability (CV)
      of 0.2-0.55%. There was no difference in recovery for the CMA 60 catheter for
      glucose when sampling times were varied. Higher flow rates resulted in decreased
      recovery. Subcutaneous tissue concentrations of glucose and urea were 4.4 mmol/l
      and 4.1 mmol/l, respectively. To conclude, this work describes an internal
      validation of our use of the microdialysis system by calibration of vials and
      catheters. Internal validation is necessary in order to be certain of adequate
      sampling times, flow rates and sampling volumes. With this in mind, the
      microdialysis technique is useful and appropriate for in vivo studies on tissue
      metabolism.

PMID- 15939566
TI  - Susceptibility testing accuracy of a CTX-M-type extended-spectrum beta-lactamase
      organism-producing population of Enterobacteriaceae: intermethod analysis for 9
      beta-lactams.
AB  - To assess the wide geographical applicability of the current and proposed
      susceptibility breakpoint criteria for 9 beta-lactam antimicrobials, the
      performance characteristics of 2 standardized methods were analyzed by testing a
      contemporary collection of 354 isolates of Enterobacteriaceae, enriched (76;
      21.5%) for extended-spectrum beta-lactamase (ESBL)-producing strains. Molecular
      characterization of 57 ESBL strains revealed that majority of the strains (94.7%)
      were CTX-M type, with a predominance (85.2%) of CTX-M-14 and -3 types, those
      types prevalent in China. Bloodstream isolates constituted 68.6% of the entire
      collection. The 9 beta-lactam antimicrobials analyzed were aztreonam, cefepime,
      cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, ceftizoxime, and
      cefuroxime. Reference broth microdilution minimal inhibitory concentration (MIC)
      results were compared to those zone diameters obtained by disk diffusion testing.
      The regression coefficient was acceptable for most antimicrobials, ranging from r
      = 0.84 (cefotetan) to r = 0.98 (cefotaxime, cefuroxime, and ceftriaxone). Using
      the current breakpoint criteria, the absolute intermethod categorical agreement
      was acceptable for 8 of the 9 antimicrobials (not cefoxitin, 85.1%) ranging from
      92.6% (cefotaxime) to 97.8% (ceftazidime). Very major (false-susceptible) and
      major (false-resistant) errors were nil (0.0%) for 5 of the beta-lactams and
      minor errors ranged from 0.8% (cefotetan) to 14.1% (cefoxitin). The proposed
      (generally lower) MIC breakpoint criteria also had acceptable intermethod
      concordance ranging from 91.6% (cefoxitin) to 99.2% (cefotaxime and ceftriaxone).
      Furthermore, an improvement in the intermethod absolute categorical agreement
      ranging from +0.8% (ceftazidime) to +6.6% (cefotaxime) was observed for 7 of 9
      antimicrobials tested, including the ESBL screening test compounds (aztreonam,
      ceftazidime, cefotaxime, and ceftriaxone). No modification of the susceptible
      breakpoint criteria, with removal of the intermediate category, was proposed for
      cefoxitin and cefuroxime, resulted in a shift of error type from minor to major
      or very major, but the categorical agreement improved (+ >or=1.2%) for both
      cephems. In conclusion, our results confirm that both the current and the
      proposed MIC breakpoint criteria with appropriately selected zone diameter
      correlates have acceptable intermethod error rates even when tested against an
      Enterobacteriaceae collection enriched with CTX-M-type ESBL-producing strains
      that are endemic in locations (China) outside the United States.

PMID- 15939567
TI  - The effectiveness of a bibliotherapy in increasing the self-management ability of
      slightly to moderately frail older people.
AB  - OBJECTIVE: Self-management ability (SMA) is the ability to obtain those resources
      necessary for the production of well-being. With age, SMA becomes increasingly
      important, if one has a large variety of resources, physical and psychosocial
      losses due to the aging process can be substituted or compensated for. This study
      examined whether an increase in SMA would ensure sustainable levels of positive
      well-being among slightly to moderately frail older people. METHODS: A
      bibliotherapy was developed to increase the SMA of slightly to moderately frail
      older people, and to help these persons to sustain a certain level of well-being.
      The effectiveness of this bibliotherapy was examined by comparing the SMA,
      mastery, and subjective well-being of 97 older people participating in the
      bibliotherapy to those of 96 older people in a delayed-treatment control
      condition. RESULTS: The bibliotherapy resulted in a significant increase in SMA
      and mastery compared to the delayed-treatment control condition, and for SMA,
      this effect still existed 6 months after the intervention. The increase in SMA
      among older people who received the bibliotherapy prevented a decline in well
      being as expected, but only in the short-term. CONCLUSION: The current findings
      show that it is possible to counteract an age-related decline in well-being, even
      with only slight to moderate levels of frailty. PRACTICE IMPLICATIONS: Cheap and
      easily accessible interventions, like the self-management bibliotherapy described
      in this article, may provide a useful addition to more traditional gerontological
      interventions.

PMID- 15939568
TI  - How well can children understand medicine related topics?
AB  - The aim of this study was to discover how well children understand medicine
      related topics and in this way to evaluate their preparedness for two-way
      communication about these matters. The data were collected by conducting 14 focus
      group discussions (FGDs) among Finnish schoolchildren aged 7-8, 10-11 and 13-14
      years. The main theme during the FGDs was the management of diseases with
      medicines. Both inductive and deductive analyses were used to analyse the data
      [Patton M. Qualitative evaluation and research methods. 2nd ed. Newbury Park:
      Sage Publications; 1990]. Children had superficial knowledge of and a negative
      attitude towards medicine use. They used medicine related vocabulary uncertainly
      implying that they do not fully comprehend all the information that they have
      gained. Children realized that there may be risks when using medicines and this
      understanding tended to increase by age. The results of this study indicate a
      need to educate children about medicines. In addition to school-based medicine
      education, health care professionals should communicate directly with children
      about their medicines at an appropriate cognitive level in order to increase
      their understanding and skills concerning health issues.

PMID- 15939569
TI  - Pre-tracheal lymph node metastasis in squamous cell carcinoma of the thoracic
      esophagus.
AB  - AIMS: To clarify the incidence of pre-tracheal lymph node metastasis in squamous
      cell carcinoma of the esophagus, and their impact on survival. METHODS: A cohort
      of 101 patients with squamous cell carcinoma of the thoracic esophagus who
      underwent esophagectomy together with 2-field lymphadenectomy including the pre
      tracheal region was analysed, retrospectively. The p-TNM staging included stage I
      in 9, stage IIa in 33, stage IIb in 4, stage III in 43, and stage IV in 12 cases.
      RESULTS: Nodal metastases were identified in 56 patients (55.4%). Subcarinal
      lymph node and pre-tracheal lymph-node metastases were found in 24 patients
      (23.8%) and 15 patients (14.9%), respectively. The 5-year cumulative survival
      rates were 26.5 and 2.5% in nodal negative and nodal positive patients,
      respectively. Patients with pre-tracheal nodal metastasis all died within 2
      years. Cox proportional hazards model in patients with nodal involvement revealed
      T-factor (p=0.0017), pre-tracheal nodal involvement (p=0.0055) and distant
      metastasis (p=0.0024) as independent prognostic factors. CONCLUSIONS: Our
      findings suggest that pre-tracheal lymph node metastasis indicates a dismal
      prognosis. Its occurrence is not unusual, especially in tumour of upper or middle
      thoracic esophagus. The subcarinal node cannot be regarded as a sentinel node of
      the pre-tracheal nodal station. Complete lymphadenectomy excluding the pre
      tracheal lymph nodes in treating esophageal cancers is only a myth.

PMID- 15939570
TI  - Future alternative therapies in a quest to halt aberrations in diabetes mellitus.
AB  - Under normal physiological conditions, euglycaemia is maintained principally by
      the homeostatic balance of insulin and glucagon which are secreted from the
      pancreas. In both type 1 and type 2 diabetes mellitus there is a substantial and
      chronic increase in the circulating glucose concentration. This elevation in
      glucose levels is accompanied by a plethora of other biochemical disturbances,
      including disruption of carbohydrate, fat and protein metabolism. Clinical
      manifestations of diabetes, which arise from the metabolic disturbances vary
      between individuals but are often a serious threat to quality and length of life.
      Pancreas transplantation (Tx) and islet modifications are methods used to restore
      endogenous insulin secretion in insulin-dependent diabetic patients. In order for
      this to be achieved successfully, however, some of the problems such as
      hyperglycemia states (> 150 mg/dl), which may harm pancreatic graft beta cells,
      immunorejection, the effects of immunosuppression, for example, must be overcome.
      Considering these problems, therefore, it seems logical that the replacement of
      the islet tissue itself, either by transplanting a vascularised pancreatic
      allograft or by transplanting modified pancreatic islet cells, provides a better
      alternative therapeutic approach than simply replacing insulin that has been
      lost. This review will show the recent development in the use of pancreatic
      islets and their modification in a quest to halt the aberrations seen in diabetes
      mellitus.

PMID- 15939571
TI  - Highly conserved regulatory elements around the SHH gene may contribute to the
      maintenance of conserved synteny across human chromosome 7q36.3.
AB  - Comparative genomic analysis reveals an exceptionally large section of conserved
      shared synteny between the human 7q36 chromosomal region and the pufferfish (Fugu
      rubripes) genome. Remarkably, this conservation extends not only to gene order
      across 16 genes, but also to the position and orientation of a number of
      prominent conserved noncoding elements (CNEs). A functional assay using zebrafish
      has shown that most of the CNEs have reproducible and specific enhancer activity.
      This enhancer activity is often detected in a subset of tissues which reflect the
      endogenous expression pattern of a proximal gene, though some CNEs may act over a
      long range. We propose that the distribution of CNEs, and their probable
      association with a number of genes throughout the region, imposes a critical
      constraint on genome architecture, resulting in the maintenance of such a large
      section of conserved synteny across the vertebrate lineage.

PMID- 15939572
TI  - A comparison of two strategies of sight word instruction in children with mental
      disability.
AB  - The aim of this research study was to compare two strategies of sight word
      instruction in children attending a school for learners with moderate to severe
      mental disability, namely modified orthography (MO) and modified orthography
      where an association was made between the modification and the traditional
      orthography (MO/TO) together with a control group (TO). Thirty-three participants
      were matched according to their gender, receptive language skills and alphabet
      knowledge and assigned to the three groups, after which they were taught 10 sight
      words by using one of the above-mentioned strategies for 2 weeks. Word
      identification scores were obtained prior to teaching, on a daily basis during
      teaching, and after 3 weeks of withdrawal to determine the retention of
      identified words. Results show that individuals with moderate to severe mental
      disability are able to learn sight words through any of the three strategies
      implemented. Although there was no statistically significant difference between
      the three groups on a 5% level, significance on a 10% level was recorded for the
      MO/TO and TO groups. The order of effectiveness as measured by group averages on
      word identification was: MO/TO, TO and MO. The clinical implication of these
      results is that by using MO/TO as teaching strategy for sight words, individuals
      with limited literacy skills would be able to derive meaning from the written
      word while forming an association between the modification and the orthography.
      This could provide early reading success and enhance word identification.

PMID- 15939573
TI  - Sensitivity analysis applied to the construction of radial basis function
      networks.
AB  - Conventionally, a radial basis function (RBF) network is constructed by obtaining
      cluster centers of basis function by maximum likelihood learning. This paper
      proposes a novel learning algorithm for the construction of radial basis function
      using sensitivity analysis. In training, the number of hidden neurons and the
      centers of their radial basis functions are determined by the maximization of the
      output's sensitivity to the training data. In classification, the minimal number
      of such hidden neurons with the maximal sensitivity will be the most
      generalizable to unknown data. Our experimental results show that our proposed
      sensitivity-based RBF classifier outperforms the conventional RBFs and is as
      accurate as support vector machine (SVM). Hence, sensitivity analysis is expected
      to be a new alternative way to the construction of RBF networks.

PMID- 15939574
TI  - Characterization of maltose and maltotriose transport in the acarbose-producing
      bacterium Actinoplanes sp.
AB  - Acarbose, a pseudomaltotetraose, is produced by strains of the genus
      Actinoplanes. The compound is an inhibitor of alpha-glucosidases and is used in
      the treatment of patients suffering from type II diabetes. The benefits of
      acarbose for the producer are not known; however, a role as carbophor has been
      proposed. Acarbose synthesis is induced in the presence of maltose and
      maltotriose. We have investigated the transport activities for these sugars in
      Actinoplanes sp. strain SN 223/29 grown on different carbon sources, including
      acarbose. Under the conditions used, Actinoplanes sp. utilized acarbose as sole
      source of carbon and energy, although growth ceased after 24 h, possibly due to
      the accumulation of a toxic degradation product in the cytosol. Maltose transport
      was observed in cells grown on each of the substrates tested except glucose.
      Maltose transport of acarbose-grown cells was inhibited by sucrose and trehalose
      and, to a lesser extent, by maltodextrins but not by acarbose. In contrast, in
      maltose/maltotriose-grown cells maltose uptake was inhibited by acarbose.
      Maltotriose uptake in these cells was less inhibited by maltose but was more
      sensitive to acarbose than in acarbose-grown cells. The Km and Vmax values of
      maltose uptake are in the range of those reported for binding protein-dependent
      sugar ATP-binding cassette (ABC) transport systems. A maltose-binding protein
      that does not bind acarbose was isolated from cells grown on either acarbose,
      glycerol or maltose. These results suggest that an acarbose-insensitive
      maltose/sucrose/trehalose transporter that also accepts maltodextrins operates in
      acarbose-grown cells while a maltodextrin transporter that accepts
      maltose/sucrose/trehalose and is moderately sensitive to acarbose is found in
      cells grown in maltose/maltotriose-containing media.

PMID- 15939575
TI  - Influence of ethanol and low pH on arginine and citrulline metabolism in lactic
      acid bacteria from wine.
AB  - The aim of this work was to study the effects of ethanol on cell growth and
      arginine and citrulline metabolism in two heterofermentative lactic acid bacteria
      from wine, and to determine their possible association with the formation of
      ethyl carbamate (EC), a carcinogenic compound. Lactobacillus hilgardii X1B is
      able to utilize arginine and citrulline, while Oenococcus oeni m can only use
      citrulline, a precursor of EC. Growth of both microorganisms was partially
      inhibited by 10 and 15% (v/v) ethanol. Specific arginine consumption by L.
      hilgardii increased when the pH value diminished from 6.5 to 3.8, but was not
      affected by an increasing ethanol concentration. However, the ethanol
      concentration affected the specific citrulline consumption of both
      microorganisms. Arginine metabolism by L. hilgardii X1B increased the amount of
      citrulline, thus allowing production of EC in the medium. Citrulline utilization
      by both microorganisms, at all pH values studied, indirectly inhibited the
      formation of EC; indeed, one of the precursors had practically disappeared after
      48 h of incubation. Due to its ability to form precursors, L. hilgardii X1B has
      the potential to contribute to EC formation, whereas citrulline utilization by O.
      oeni m in the presence of ethanol may contribute to diminishing the formation of
      EC. Rapid degradation of citrulline in the presence of ethanol by O. oeni m is
      important from a toxicological point of view, because it is important to keep the
      EC levels as low as possible.

PMID- 15939576
TI  - Characterization of long-chain fatty-acid-degrading syntrophic associations from
      a biodegraded oil reservoir.
AB  - Molecular methods were used to characterize stearate- and heptadecanoate
      degrading methanogenic consortia enriched from a low-temperature biodegraded oil
      field. Stearate- and heptadecanoate-degrading cultures formed acetate. Growth on
      heptadecanoate was also accompanied by the production of propionate. These
      fermentation products were transiently accumulated at the beginning of the
      exponential phase and were further consumed with the concomitant production of
      methane. Clone libraries of bacterial and archaeal 16S rRNA genes were generated
      for each stable enrichment. Our 16S rRNA gene-cloning analysis combined with
      fluorescence in situ hybridization revealed that the predominant microorganisms
      in the associations were affiliated with a clone cluster close to the genus
      Syntrophus in the class "Deltaproteobacteria" and with the methanogenic genera
      Methanocalculus and Methanosaeta. Confocal scanning laser microscopy showed that
      the bacterial and archaeal cells formed compact aggregates around the insoluble
      substrates. No layered structure was observed in the aggregate organization. This
      study reports the presence of new fatty-acid-degrading syntrophic consortia in
      oil fields and our results suggest that such associations may have an important
      ecological role in oil fields under methanogenic conditions.

PMID- 15939577
TI  - Absence of hippocampal volume differences in survivors of the Nazi Holocaust with
      and without posttraumatic stress disorder.
AB  - It remains unclear whether smaller hippocampal volume is a consistent feature of
      chronic posttraumatic stress disorder (PTSD) and whether it accounts for the
      associated memory deficits observed in this illness. Hippocampal volume,
      comparison regions and memory performance were examined in Holocaust survivors
      with PTSD (PTSD+: n=14; 5 men, 9 women) and without PTSD (PTSD-: n=13; 6 men, 7
      women) and a non-exposed control group of healthy Jewish adults (n=20; 13 men, 7
      women). The subjects had medical examinations, high-resolution magnetic resonance
      imaging, and memory testing. PTSD+ subjects had poorer memory performance than
      non-exposed subjects and PTSD- subjects, but they did not differ from either
      group in right or left hippocampal volume when gender and head size were taken
      into account. Older age and smaller left hippocampal volume were more strongly
      associated in the PTSD+ group than in the PTSD- groups. Holocaust survivors had
      larger superior temporal gyral and lateral temporal lobe volumes bilaterally than
      non-exposed subjects. Smaller hippocampal volume is not invariably associated
      with chronic PTSD and does not explain the substantial explicit memory impairment
      observed in Holocaust survivors with this disorder. Larger temporal lobe volumes
      may be associated with early traumatization and survival or may reflect some
      other characteristic of Holocaust survivors.

PMID- 15939578
TI  - The influence of microbial metabolites on human intestinal epithelial cells and
      macrophages in vitro.
AB  - Microbial metabolites may influence the metabolic integrity of intestinal
      epithelial cells and induce mucosal immune responses. Therefore, we investigated
      the effects of the microbial metabolites butyrate, iso-valerate, and ammonium on
      Caco-2 cells and macrophages. Barrier functioning was determined by measuring
      transepithelial electrical resistance and basolateral recoveries of metabolites.
      The barrier function of Caco-2 cells remained intact after exposures. Basolateral
      recoveries ranged from 6.2% to 15.2%. Tumour necrosis factor-alpha and
      interleukin-10 were measured to determine immune reactions. The Caco-2 cells did
      not secrete both cytokines. Physiological concentrations of butyrate and iso
      valerate stimulated the secretion of tumour necrosis factor-alpha and suppressed
      the secretion of interleukin-10 by macrophages that are not protected by an
      epithelial barrier. In contrast, ammonium concentrations as high as those
      produced by microbiotas of IBD patients suppressed the release of both cytokines
      when the barrier function is impaired.

PMID- 15939579
TI  - [Massive inhalation of mould and gravels].

PMID- 15939580
TI  - Differences in COPD care among doctors who control the disease: general
      practitioner vs. pneumologist.
AB  - AIM: To assess the role of doctors who patients report as responsible of their
      disease, in moderate-severe chronic obstructive pulmonary disease (COPD),
      describing characteristics of patients and treatments use according to each type
      of doctor, and relating it to the way of access to hospital at the time of an
      exacerbation. MATERIALS/PATIENTS AND METHODS: A systematic sample of 1:2 patients
      admitted for a COPD exacerbation during 1 year in four tertiary hospitals in the
      Barcelona area, Spain, was recruited. Information about health services was
      obtained by an administered questionnaire. RESULTS: A total of 346 patients were
      recruited: mean age 69 (+/-9) years, percent of predicted FEV(1) of 35 (+/-16)%,
      PO(2) of 64 (+/-13)mmHg. At the time of admission, 17% of patients reported being
      controlled by a general practitioner (GP) and 56% by a pneumologist whereas 21%
      reported its COPD not being under the regular control of any doctor. Patients not
      controlled by a pneumologist did not suffer from milder COPD than the remaining,
      but were less likely to receive pharmacological and non-pharmacological
      treatments and less likely to perform correctly the inhalation manoeuvres. During
      the course of the exacerbation 70% of patients reported a visit to a hospital
      emergency room department without a previous medical visit, this proportion being
      higher among those controlled by a pneumologist. CONCLUSIONS: Lack of control and
      variability in the patterns of care among patients controlled by different types
      of physicians are common in moderate-to-severe COPD patients admitted for a COPD
      exacerbation, despite the lack of differences in COPD severity. Medical control
      of COPD patients needs more investigation and a wider inclusion in international
      guidelines.

PMID- 15939581
TI  - Home mechanical ventilatory support in patients with restrictive ventilatory
      disorders: a 48-year experience.
AB  - We performed a retrospective analysis to the effects of negative pressure
      ventilation (NPV), tracheal intermittent positive pressure ventilation (TIPPV),
      and nasal intermittent positive pressure ventilation (NIPPV, volume or pressure
      controlled ventilatory mode), in 114 patients with restrictive ventilatory
      disorders instituted in our hospital from 1956 until 2005. The patients were
      assigned on "ad hoc" basis to NPV, TIPPV, or NIPPV. All patients were subdivided
      in an idiopathic kyphoscoliosis group (IK, n=64), a post-poliomyelitis syndrome
      group (PP, n=30), or a miscellaneous group (M, n=20). The patients in the PP
      group had higher survival rates compared to the IK patients (P<0.05), while the M
      patients had the lowest survival rates (P<0.01). Both NPV (P<0.01) and TIPPV
      (P<0.05) lead to a decrease in PaCO2 after 9 months compared to baseline. This
      decrease in PaCO2 was still present after 5 years NPV (P<0.001) and TIPPV
      (P<0.05). NIPPV lead to an improvement in pulmonary function (P<0.05) and
      arterial blood gases (P<0.001) after 9 months compared to baseline. After 5 years
      NIPPV, the arterial blood gases were still significantly improved compared to
      baseline (P<0.01). Both volume-controlled and pressure-controlled ventilation
      improved pulmonary function and arterial blood gases. CONCLUSION: Long-term home
      mechanical ventilatory support by both NPV and positive pressure ventilation is
      effective in patients with IK, PP syndrome, and a M group, even after a period of
      5 years.

PMID- 15939582
TI  - Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine
      house dust in healthy subjects.
AB  - BACKGROUND: Inhalation of swine house dust induces acute airway inflammation and
      increased bronchial responsiveness in healthy subjects. OBJECTIVE: The aim of the
      study was to investigate whether 5-lipoxygenase products such as leukotrienes may
      have a role in this reaction. METHODS: Twenty-three healthy subjects were
      randomised into two groups receiving treatment with either zileuton (600 mg) or
      placebo four times a day. After 5 days of treatment, all subjects were exposed
      for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and
      mediators in nasal lavage (NAL), blood and urine were measured before and after
      the exposure. RESULTS: The exposure induced an increased bronchial responsiveness
      to methacholine in both groups with 2-3 doubling concentration steps, no
      significant difference between treatments. Leukotriene E(4) in urine increased
      significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean
      (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol
      creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of
      LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05
      vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two
      fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in
      placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell
      participation. Neutrophil counts and levels of IL-6 in peripheral blood increased
      in both groups, with a significantly larger increase in zileuton treated subjects
      (P<0.05 and P<0.001, respectively compared to placebo). CONCLUSIONS: Pre
      treatment with clinically recommended doses of the 5-lipoxygenase inhibitor
      zileuton did not affect the increase of bronchial reactivity induced by swine
      dust exposure. The intervention totally abolished the LTB(4) release in NAL
      fluid, but only partially inhibited the formation of leukotrienes as monitored by
      urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood
      in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro
      inflammatory effects.

PMID- 15939583
TI  - Antenatal anaesthetic assessment of high-risk pregnancy: a survey of UK practice.
AB  - BACKGROUND: Anaesthetists are frequently involved in the management of high-risk
      pregnancy. Antenatal referral permits time to prepare an appropriate management
      plan for labour and delivery. This survey looked at current methods of referral
      in the UK and the role of a formal clinic. METHOD: A postal questionnaire was
      sent to lead consultant anaesthetists of 256 UK obstetric units enquiring into
      methods of referral for high-risk pregnancy. RESULTS: Replies were received from
      196 units (response rate 77%). Only 30% of units that responded ran a formal
      anaesthetic pre-assessment clinic, the remaining 70% relying on ad hoc referrals
      of high-risk cases. Larger units were more likely to run formal clinics. Some
      units wishing to introduce a formal clinic had not been able to do so because of
      financial constraints. CONCLUSION: Most hospitals were satisfied with current
      arrangements for referral of high-risk pregnancy. A mechanism for anaesthetic
      referral of high-risk pregnancy is vital, but in many units is not via a formal
      clinic.

PMID- 15939584
TI  - A decade of CASP: progress, bottlenecks and prognosis in protein structure
      prediction.
AB  - For the past ten years, CASP (Critical Assessment of Structure Prediction) has
      monitored the state of the art in modeling protein structure from sequence.
      During this period, there has been substantial progress in both comparative
      modeling of structure (using information from an evolutionarily related
      structural template) and template-free modeling. The quality of comparative
      models depends on the closeness of the evolutionary relationship on which they
      are based. Template-free modeling, although still very approximate, now produces
      topologically near correct models for some small proteins. Current major
      challenges are refining comparative models so that they match experimental
      accuracy, obtaining accurate sequence alignments for models based on remote
      evolutionary relationships, and extending template-free modeling methods so that
      they produce more accurate models, handle parts of comparative models not
      available from a template and deal with larger structures.

PMID- 15939585
TI  - Aromatase inhibitors for therapy of advanced breast cancer.
AB  - In postmenopausal women with advanced breast cancer, numerous phase III trials
      have been performed comparing the third-generation non-steroidal aromatase
      inhibitors (NS-AIs) anastrozole and letrozole and the steroidal AI (S-AI)
      exemestane in the "first-line" setting against tamoxifen and in the "second-line"
      setting against megestrol acetate. In both settings, the AIs were at least as
      efficacious or superior in some endpoints with a preferable toxicity profile
      including a lower incidence of thrombotic events. Relatively small differences in
      potency between the three AIs have been identified and it has not been
      demonstrated that these differences have clinical implications. The recent
      establishment of the value of AIs in the adjuvant setting for postmenopausal
      women will impact on their utilization in advanced disease. In premenopausal
      women the third-generation AIs have not been studied as monotherapy and there is
      a paucity of data in combination with ovarian function suppression in the
      advanced disease setting. The main area of future investigations for the AIs in
      premenopausal women will be in the adjuvant therapy setting in combination with
      suppression of ovarian function.

PMID- 15939586
TI  - Aromatase and comparative response to its inhibitors in two types of endometrial
      cancer.
AB  - Aromatase activity (AA) was evaluated totally in 80 tumors collected from primary
      endometrial cancer (EC) patients. All patients were divided into cases belonging
      to the types I or II of EC (respectively, 50 and 30 observations). Samples of
      malignant endometrium from type II demonstrated inclination to the higher AA in
      comparison with type I samples; the difference reached level of statistical
      significance in non-smoking patients (p=0.02). Although no positive correlation
      was revealed between AA in EC tissue and percentage of cells with DNA damage in
      normal endometrium from the same patients, the rate of DNA damage (percent of
      comets, comet's tail average length, etc.) was higher in intact endometrium
      collected from patients with type II of the disease. In 19 tumor samples, CYP19
      gene expression was evaluated by RT-PCR and level of mRNA signal demonstrated
      positive correlation with AA (R(s)=+0.63, p=0.05) in the whole this material. Of
      note, though, CYP19 mRNA expression was not revealed in six cases, and all of
      them belonged to the type I of disease. Finally, in 23 EC patients (15 with type
      I and 8 with type II of the disease) effects of 2 weeks treatment with letrozole
      (10 pts) and exemestane (13 pts) were evaluated in neoadjuvant setting. Although
      diminishing of endometrial M-echo signal and the increases in FSH and LH
      concentration after treatment were more pronounced in type I patients, decrease
      in tumor PR content (p=0.04) was more revealing in patients with type II of EC;
      besides, the decreases in AA in tumor tissue by the end of treatment were noted
      predominantly in patients with lower body weight (BMI <27.5). Thus, although type
      II of EC is frequently considered as hormone-independent, increased ability of
      this type of the tumor to estrogen biosynthesis (at CYP19 gene and protein level)
      may lead to the reconsideration of such conclusion and warrants further
      investigation. The search of possible ethnic differences in AA and in the
      biologic response to aromatase inhibitors in EC can be of importance too.

PMID- 15939587
TI  - 1,25-Dihydroxyvitamin D3 induces splenocyte apoptosis and enhances BALB/c mice
      sensitivity to toxoplasmosis.
AB  - The hormonal form of Vitamin D, 1,25-dihydroxyvitamin D3, is well known for its
      immunosuppressive, anti-proliferative and pro-apoptotic activities. In the
      present work, we studied the effect of 1,25-dihydroxyvitamin D3 on Toxoplasma
      gondii-infected mice. We observed that 1,25-dihydroxyvitamin D3 reduces the
      survival rate of infected mice by up to 37% at day 10 post-infection compared to
      untreated infected mice (P < 0.0001). IFN-gamma and IL-12p40 levels were
      significantly reduced by 1,25-dihydroxyvitamin D3 in infected mice sera
      indicating an inhibition of Th-1-type cytokines. CD4+ T lymphocyte and splenocyte
      counts were also reduced following 1,25-dihydroxyvitamin D3 treatment and a
      marked induction of apoptosis, accompanied with down-regulation of the anti
      apoptotic proteins Bcl-2 and Bcl-X(L), was observed. The above results indicate
      that 1,25-dihydroxyvitamin D3 induces splenocyte apoptosis and enhances host
      susceptibility to toxoplasmosis.

PMID- 15939588
TI  - Continuous electricity production from artificial wastewater using a mediator
      less microbial fuel cell.
AB  - A microbial fuel cell (MFC) was optimized in terms of MFC design factors and
      operational parameters for continuous electricity production using artificial
      wastewater (AW). The performance of MFC was analyzed through the polarization
      curve method under different conditions using a mediator-less MFC. The highest
      power density of 0.56 W/m2 was achieved with AW of 300 mg/l fed at the rate of
      0.53 ml/min at 35 degrees C. The power per unit cell working volume was 102 mW/l,
      which was over 60 times higher than those reported in the previous mediator-less
      MFCs which did not use a cathode or an anode mediator. The power could be stably
      generated over 2 years.

PMID- 15939589
TI  - Extraction of cashew (Anacardium occidentale) nut shell liquid using
      supercritical carbon dioxide.
AB  - This work investigated the extraction of cashew nut shell liquid (CNSL) using
      supercritical carbon dioxide (SC-CO(2)). Effects of process parameters such as
      extraction pressure, temperature and flow rate of SC-CO(2) were investigated. The
      yield of CNSL increased with increase in pressure, temperature and mass flow rate
      of SC-CO(2). However, under different operating conditions, the composition of
      CNSL varied. The study of physical properties and chemical composition of the oil
      obtained through super critical fluid extraction (SCFE) showed better quality as
      compared to the CNSL obtained through thermal route. Experimental results were
      compared with diffusion based mass transfer model. Based on this simple model,
      extraction time was optimized.

PMID- 15939590
TI  - Impact of long and short term irrigation of a sodic soil with distillery effluent
      in combination with bioamendments.
AB  - The study reports the effects of irrigation of a sodic soil with post methanation
      effluent (PME) of a distillery. Impact of long term effluent irrigation in the
      field (10 years) and short term effluent irrigation using different doses of PME
      in the laboratory (30 days) was studied in combination with three bioamendments
      i.e. farmyard manure, brassica residues and rice husk. Impact on various soil
      properties like EC, pH, total organic carbon (TOC), total Kjeldahl nitrogen
      (TKN), available phosphorus, exchangeable K, Na, Ca, Cl, microbial population and
      soil enzyme activities were studied. Long term application of PME proved useful
      in significantly increasing TOC, TKN, K, P and soil enzymatic activities in the
      soil but tended to build up harmful concentration of Na, that could be chelated
      by bioamendments. In short terms studies, application of 50% PME along with
      bioamendments proved to be the most useful in improving the properties of sodic
      soil and also favoured successful germination and improved seedling growth of
      pearl millet.

PMID- 15939591
TI  - The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as
      protein maturation and quality-control tags.
AB  - The majority of proteins that traverse the secretory pathway receive asparagine
      (Asn)-linked glycosylations. Glycans are bulky hydrophilic modifications that
      serve a variety of structural and functional roles within the cell. Here, we
      review the recent growing knowledge on the role of Asn-linked glycans as
      maturation and quality-control protein tags in the early secretory pathway. The
      carbohydrate composition encodes crucial information about the structure,
      localization and age of glycoproteins. The "glycan code" is encoded by a series
      of glycosidases and carbohydrate transferases that line the secretory pathway.
      This code is deciphered by carbohydrate-binding proteins that possess distinct
      carbohydrate binding properties and act as molecular chaperones or sorting
      receptors. These glycosidases and transferases work in concert with resident
      secretory pathway carbohydrate-binding proteins to form a network that assists in
      the maturation and trafficking of both native and aberrant glycoproteins within
      the cell.

PMID- 15939592
TI  - Biomechanics of the knee joint in flexion under various quadriceps forces.
AB  - Bioemchanics of the entire knee joint including tibiofemoral and patellofemoral
      joints were investigated at different flexion angles (0 degrees to 90 degrees )
      and quadriceps forces (3, 137, and 411 N). In particular, the effect of changes
      in location and magnitude of restraining force that counterbalances the isometric
      extensor moment on predictions was investigated. The model consisted of three
      bony structures and their articular cartilage layers, menisci, principal
      ligaments, patellar tendon, and quadriceps muscle. Quadriceps forces
      significantly increased the anterior cruciate ligament, patellar tendon, and
      contact forces/areas as well as the joint resistant moment. Joint flexion,
      however, substantially diminished them all with the exception of the
      patellofemoral contact force/area that markedly increased in flexion. When
      resisting extensor moment by a force applied on the tibia, the force in cruciate
      ligaments and tibial translation significantly altered as a function of magnitude
      and location of the restraining force. Quadriceps activation generated large ACL
      forces at full extension suggesting that post ACL reconstruction exercises should
      avoid large quadriceps exertions at near full extension angles. In isometric
      extension exercises against a force on the tibia, larger restraining force and
      its more proximal location to the joint substantially decreased forces in the
      anterior cruciate ligament at small flexion angles whereas they significantly
      increased forces in the posterior cruciate ligament at larger flexion angles.

PMID- 15939593
TI  - Experimental studies on excitation functions of the proton-induced activation
      reactions on yttrium.
AB  - Proton-induced activation cross-sections were measured for the
      (89)Y(p,x)(89,88,86)Zr, (89)Y(p,x)(88,87,87 m,86)Y, (89)Y(p,x)(85,83,82)Sr and
      (89)Y(p,x)(84,83)Rb reactions by a stacked foil technique in the energy range 15
      80 MeV which was covered by two separate measurements for 15-50 and 32-80 MeV
      energy range with 50 and 80 MeV incident protons. The differences between the
      results of two irradiations were found within 6% in the overlapping energy
      regions. The production yields for the long-lived products like (88)Zr, and (88)Y
      are significantly larger than that of (nat)Mo+p, (nat)Nb+p and (nat)Zr+p
      processes. The productions of the medical isotopes, (85)Sr and (83)Sr are also
      effective by Y+p process using an 80 MeV beam. Thick target integral yields were
      also deduced using the measured cross-sections. The (87)Y, (88)Y, (88)Zr and
      (89)Zr radionuclides have suitable yields and decay characteristics important for
      thin-layer activation (TLA) analysis.

PMID- 15939594
TI  - Tracheomalacia in oesophageal atresia: morphological considerations by endoscopic
      and CT study.
AB  - OBJECTIVE: A Tracheomalacia complicates 11-33% of cases of Oesophageal Atresia
      with distal Tracheo-Oesophageal Fistula. The lesion generally involves only the
      thoracic segment of the trachea, and it has close anatomical relationships with
      the mediastinal structures, specially with the aortic arch. We therefore tried to
      define the most important morphotypes of tracheobronchial malacia by using
      dynamic fiberoptic bronchoscopy (DFB) and spiral multilayer computed tomography
      (CT). METHODS: Between 1999 and 2003 we studied 40 children from two different
      institutions who had been operated on at birth for oesophageal atresia. All
      patients were been submitted to DFB, and the positive cases underwent examination
      by CT with an iodinated contrast medium. CT angiographic images of great vessels
      and multiplanar and three-dimensional images of the airways (virtual broncoscopy
      and broncography) were obtained for morphological evaluation. RESULTS: Twenty
      five patients (62%) tested positive for malacia using DBF and all were also
      confirmed by CT study. In 11 cases (46%), the malacia was located at the thoracic
      section of the trachea, which was occluded by compression of the aorto-innominate
      complex. A simple intrinsic tracheomalacia without any vascular compression was
      present in eight cases (33%), while in five cases (21%), the malacia was complex.
      CONCLUSIONS: A correct morphological analysis of the malformed segment permitted
      'tailored surgery' for each individual patient, allowing us to take account of
      the type of malacia, its length, and the compressive action exercised by the
      mediastinal great vessels.

PMID- 15939595
TI  - Does size matter? Larger Blalock-Taussig shunt in the modified Norwood operation
      correlates with better hemodynamics.
AB  - OBJECTIVE: Excess pulmonary to systemic blood flow ratio (Qp/Qs) correlates with
      hemodynamic instability and mortality after modified Norwood operation. Studies
      suggest that maximal oxygen delivery occurs at a Qp/Qs of around 1. The use of a
      rather small modified Blalock-Taussig shunt (MBTS) is believed to achieve this
      goal. However, optimal MBTS size with respect to postoperative hemodynamics
      remains unclear. METHODS: Between 2/2002 and 2/2004, 20 consecutive patients
      underwent Norwood operation; there were 19 operative survivors: nine with a
      normalized MBTS area (NSA) > or = 3.3 mm2/kg (group 1) and 10 with NSA < 3.3
      mm2/kg (group 2). Mean arterial pressure (MAP) and common atrial pressures (CAP),
      arterial and superior vena cava oxygen saturations, urinary output and inotropes
      recorded for the postoperative hours 0, 6, 12, 18, 24 and 48 were analyzed.
      RESULTS: Hospital mortality was 11.1% (1/9) in group 1 and 30% (3/10) in group 2
      (P = 0.6). For group 1 significantly higher MAP of 52+/-1.3 versus 46+/-0.8 mmHg
      (P < 0.001), higher urinary output of 6.2+/-0.5 versus 4.2+/-0.5 ml/kg per h (P <
      0.01), lower CAP of 8+/-0.3 versus 10+/-0.4 mmHg (P < 0.001), and lower heart
      rate of 145+/-2.6 versus 160+/-1.6 bpm were recorded than for group 2. In group
      1, lower doses of adrenaline (0.03+/-0.01 versus 0.15+/-0.01 microg/kg per min, P
      < 0.05) and noradrenaline (0.01+/-0.01 versus 0.13+/-0.04 microg/kg per min, P <
      0.01) were needed. Although Qp/Qs was more often calculated to be > 1.5 in group
      1 (51 versus 31%), arteriovenous oxygen difference and oxygen excess factor were
      not significantly different, indicating similar oxygen delivery. CONCLUSIONS:
      Monitoring of the central venous oxygen saturations and application of afterload
      reduction in cases of high Qp/Qs allows the insertion of a larger MBTS without
      association with lower oxygen delivery. In fact, better hemodynamic status with
      less inotropic support was noted with a larger MBTS early after Norwood
      operation.

PMID- 15939596
TI  - Gender and early mortality after lung resection in elderly.

PMID- 15939597
TI  - Simultaneous repair of post-infarct ventricular septal defect and coronary artery
      bypass grafting.

PMID- 15939598
TI  - From the dis-covered stent to the valved stent: you learn from your mistakes!!

PMID- 15939599
TI  - Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and
      lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR.
AB  - OBJECTIVE: Detection of disseminated tumor cells in mediastinoscopic biopsies
      could improve staging and might be helpful concerning indications for neoadjuvant
      therapy regimens. This prospective study was performed to evaluate a simple and
      observer-independent polymerase chain reaction (PCR)-based method for the
      detection of disseminated tumor cells in regional lymph nodes. METHODS: Lymph
      nodes of 32 consecutive patients without neoadjuvant therapy were removed by
      systematic lymphadenectomy during resection of primary NSCLC. One hundred of
      these lymph nodes were cut into two equal halves which were examined using either
      routine histopathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT
      PCR amplification of cytokeratin 19 (CK19) transcripts was applied for the
      detection of tumor cell-specific RNA. We differentiated between illegitimate
      marker gene transcription and cancer-specific expression by using a cut-off value
      that was obtained from the analysis of 18 lymph nodes of patients with benign
      lung diseases. Subsequent to the evaluation of qRT-PCR, a pilot project with five
      additional patients was conducted to examine 19 mediastinoscopic biopsies, which
      were cut into two equal halves and proceeded as described above. RESULTS: Ninety
      four (94%) lymph nodes were tumor-free by histopathology. qRT-PCR detected
      disseminated tumor cells in 26 (28%) of these lymph nodes. All of the remaining
      six lymph nodes that were judged by the pathologist to contain tumor cells
      exhibited CK19 transcripts. Twenty-three patients had a pN0 status. qRT-PCR
      detected disseminated tumor cells in 13 (56%) of these pN0 patients. The
      mediastinoscopic biopsies showed disseminated tumor cells in four (21%) out of 19
      histopathologically tumor-free samples. CONCLUSIONS: CK19 qRT-PCR is a sensitive
      and specific tools for the detection of disseminated tumor cells in regional
      lymph nodes of patients with operable NSCLC. Further studies are required to
      asses if this molecular method might improve mediastinoscopic staging.

PMID- 15939601
TI  - Factors affecting regression of mitral regurgitation following isolated coronary
      artery bypass surgery.
AB  - OBJECTIVE: Fate of MR following CABG is variable. Predictors of MR regression
      following CABG alone are not known. METHODS: From our surgical registry, CABG
      patients with both pre-operative and post-operative resting echocardiograms at
      our institution were screened. Of the 523 patients identified, 92 had 3+ (n = 65)
      or 4+ (n = 27) MR on the pre-operative echocardiogram on a 0-4 scale, who had
      isolated CABG. MR regression was correlated with clinical, operative,
      electrocardiographic and echocardiographic variables. RESULTS:  PATIENT
      CHARACTERISTICS: age 68+/-11 years, 62% male, and LVEF 37+/-15%. MR grade
      decreased from 3.3+/-0.5 to 2.3+/-1.2 post-CABG. Residual 3 or 4+ MR post-CABG
      was present in 43 (47%) patients. Regression of MR (n=49) was associated with
      reductions in LV end-diastolic (P = 0.006) and end-systolic (P = 0.0005)
      dimensions, improvement in LVEF (P = 0.01), longer cross-clamp time (P = 0.04),
      use of beta-blockers (P = 0.04) and lower presence of CVA as a possible marker of
      lower atherosclerotic burden (P = 0.03). There was a trend towards increased
      mortality (P = 0.3) with residual 3-4+ MR over a mean follow-up of 3.9 years.
      CONCLUSIONS: In nearly half of patients with 3-4+ MR, MR does not regress with
      CABG alone. Residual MR may be associated with increased mortality. Regression of
      MR is related to LV size reduction and improvement in LV function. Presence of
      myocardial viability, adequate revascularization, lack of excessive
      atherosclerotic burden and therapy with beta-blockers and ace-inhibitors may be
      critical for MR regression following CABG alone.

PMID- 15939602
TI  - Recurrent pulmonary mucinous cystadenoma.
AB  - A pulmonary mucinous cyst adenoma is rare and there has been no report of the
      recurrence. We report a case of a 56-year-old female who had recurrent pulmonary
      mucinous cystadenoma. She had previously received a partial resection of the lung
      for a pulmonary mucinous cystadenoma 20 years ago. On this admission, a chest X
      ray and CT scan revealed a large pulmonary mass, and a lung resection was
      performed. The resected lesion was histologically confirmed as mucinous
      cystadenoma. At 2 years to date after the second operation, the patient has no
      recurrence.

PMID- 15939603
TI  - Pacemaker implantation after congenital heart surgery: risk and prognosis in a
      population-based follow-up study.
AB  - OBJECTIVE: Although earlier a feared complication of congenital cardiac surgery,
      the incidence of heart-block and sinus node dysfunction has been lowered to 1-4%
      due to improved surgical techniques and better anatomical understanding of the
      cardiac conduction system. Development of feasible pacemaker technologies has
      further lowered mortality and morbidity. However, pacemaker implantation in
      paediatric patients is in itself associated with significant morbidity due to
      pacemaker system failure and replacement. The aim of the present study was to
      examine prognostic factors of mortality, failure of systems and timing of
      implantation after surgery in post-surgical pacemaker patients. METHODS: We
      carried out a historical prospective follow-up analysis of all patients (age less
      than 18 years) who underwent pacemaker implantation due to post-surgical heart
      block or sinus node dysfunction in the period 1981-2002 at our institution. Data
      was extracted from the Danish Pacemaker Register and hospital records. Kaplan
      Meier survival time estimates and Cox proportional hazards analysis (Relative
      Risk, RR) were used to identify prognostic factors. RESULTS: High RACHS score
      (RR, 16.57), low age at implantation (RR, 0.22), low age at operation (RR, 0.06)
      and epicardial lead (RR, 0.18) were significant predictors for early mortality.
      Similarly, high RACHS score (RR, 4.84), low age at implantation (RR, 0.32), low
      age operation (RR, 0.38) and epicardial lead (RR, 0.40) were significant
      predictors failure of 1st pacemaker system. CONCLUSIONS: We identified a number
      of prognostic factors of patient mortality and failure of systems. One factor,
      high RACHS score, was previously shown to predict mortality and length of ICU
      stay in paediatric cardiac surgery; however, this study is the first to show a
      correlation between RACHS score and mortality as well as failure of pacemaker
      systems. This may have future implications for preoperative risk stratification
      of patients and counselling of parents to patients with congenital heart disease.

PMID- 15939604
TI  - Atypical presentation of mature teratoma mimicking hydatidosis.

PMID- 15939605
TI  - Operative VATS: the need for a different intrathoracic approach.

PMID- 15939606
TI  - Aortic arch embolization of an Amplatzer occluder after an atrial septal defect
      closure: hybrid operative approach without circulatory arrest.
AB  - Percutaneous closure of the secundum type atrial septal defects is becoming
      increasingly popular. We report the case of a 49-year-old man who presented for
      an unusual embolization of an Amplatzer occluder (AO) 6 weeks after a
      percutaneous closure of his secundum type atrial septal defect. Emergency cardiac
      surgery was performed and the device was safely removed by a combined surgical
      and endovascular approach with no need of circulatory arrest or of profound
      hypothermia.

PMID- 15939608
TI  - Maze III-still the holy grail?

PMID- 15939609
TI  - Giant free floating left atrial thrombus.

PMID- 15939610
TI  - Stem cell research and cell transplantation for myocardial regeneration.
AB  - Several human organs are not capable of functional regeneration following a
      tissue defect and react with scar formation. In stem cell transplantation,
      undifferentiated or partly differentiated precursor cells are applied to
      defective tissue for therapeutic regeneration. After promising preclinical
      investigations, the transplantation of autologous stem cells for myocardial
      infarction treatment is being transferred to clinical use. Mesenchymal stem cells
      and endothelial precursor cells derived from the bone marrow or circulating blood
      as well as skeletal myoblasts are employed in clinical trials. Furthermore,
      indications for cell transplantation and delivery routes vary considerably
      throughout current investigations. Initial results suggest a potential for
      restoration of cardiac function in stem cell-treated patients; however, the
      mechanisms are not fully understood. This overview will focus on objectives,
      recent achievements, and future perspectives of diverse stem cell transplantation
      approaches.

PMID- 15939611
TI  - Skeletonized bilateral internal mammary arteries for non-elective surgical
      revascularization in unstable angina.
AB  - OBJECTIVE: The aim of this study was to evaluate the feasibility, safety and
      outcome of skeletonized bilateral internal mammary arteries (BIMA) in patients
      with unstable angina (UA) undergoing non-elective myocardial revascularization.
      METHODS: Between January 1997 and December 2003, 758 patients, mean age 62+/-12
      years, underwent non-elective coronary artery bypass grafting (CABG) for unstable
      angina. Two hundred and five (27%) were operated emergently and 503 (73%)
      urgently. BIMA were employed in 320 (42%) patients (Group B) and isolated left
      IMA and/or saphenous vein grafts in the remaining 438 (58%) patients (Group M).
      RESULTS: In-hospital mortality (B = 5.9% and M = 5.3%), and perioperative
      myocardial infarction (B = 2.2%; M = 1.96%) were similar between the two groups
      (P = ns). Actuarial survival at 1, 3 and 7 years was 98.7, 97.5 and 96.2% in B
      and 99, 94.3 and 88.4% in M (P < 0.05 at 7 years follow-up). At 7 years follow
      up, the event-free cardiac survival (92 vs. 87%, P = 0.021), angina-free survival
      (98.6 vs. 94%, P = 0.039), reoperation-free cardiac survival (98 vs. 95%, P =
      0.04) and infarct-free cardiac survival (98.7 vs. 96%, P = 0.05) were better in
      Group B. Multivariate analysis identified age > 65 years (P = 0.02), LVEF < 35%
      (P = 0.01), > 1 ischemic irreversible area (P = 0.03) as independent predictors
      for late deaths, while the use of the LIMA (P=0.006) and both mammary arteries
      (P=0.001) decreased the risk of late deaths. CONCLUSIONS: The use of BIMA in non
      elective CABG for UA is safe and effective. Mid-term outcome, however, are
      superior with improved freedom from cardiac death, from coronary reintervention
      and from myocardial infarction.

PMID- 15939612
TI  - The myocardial band: simplicity can be a weakness.

PMID- 15939613
TI  - The effect of chronic steroid therapy on outcomes following cardiac surgery: a
      propensity-matched analysis.
AB  - OBJECTIVE: Steroids are beneficial in reducing the inflammatory response
      accompanying surgery with cardiopulmonary bypass. However, chronic steroid
      therapy has been implicated as a risk factor for abdominal complications and
      mortality following surgery. We assessed the impact of chronic steroid therapy
      had on outcome following cardiac surgery. METHODS: During the period January 1999
      to March 2003 there were 98 patients on chronic steroid therapy (Group S) who
      underwent cardiac surgery at our institution. These patients were matched with a
      control group of 98 patients who were not on steroids (Group C). A propensity
      score was used to perform the matching. The C statistic for this model was 0.72.
      RESULTS: Ninety (93.7%) of the 98 patients in Group S had been on oral
      prednisolone for a median of 9.5 years (25th and 75th percentile of 5 and 12
      years) with a median dose of 5mg (25th and 75th percentile of 4 and 8.75 mg).
      Preoperative characteristics were well matched between both groups. There was no
      difference in the post-operative outcome between the two groups with respect to
      mortality, stroke, renal failure, abdominal complications, wound infections,
      requirement for inotropic support and myocardial infarction. Patients in Group S
      were more likely to develop atrial arrhythmias and to require prolonged
      ventilation, although this did not reach statistical significance. CONCLUSIONS:
      Chronic steroid therapy was not associated with increased mortality or overall
      morbidity following cardiac surgery. However, patients on chronic steroids may be
      at greater risk of developing atrial arrhythmias or of requiring prolonged
      ventilation.

PMID- 15939614
TI  - Heparin induced thrombocytopenia causing an isolated cardiac free floating
      thrombosis.

PMID- 15939617
TI  - Use of a modified endobronchial tube for mechanical ventilation of patients with
      bronchopleural fistula.
AB  - Mechanical ventilation in patients with bronchopleural fistula after lung
      resection is a major problem, as it causes increase of the air-leak, complicates
      the healing process and makes residual lung tissue ventilation difficult. We
      present two cases in which the use of a modified double lumen endobronchial tube
      improved ventilation and eliminated the fistula air-leak. We used a right-sided
      double lumen sher-i-bronch tube (Sheridan Catheter Corp., USA). This method, by
      blocking the airflow through the fistula, may facilitate the expansion of the
      residual lung parenchyma. In both the patients treated with this technique, we
      obtained a good expansion of the residual parenchyma. Despite the procedure, the
      first patient died of septic shock; in the second patient, we achieved
      improvement of the respiratory function, the weaning from the mechanical
      ventilation, and thereafter, the healing of the fistula. The use of a modified
      double lumen sher-i-bronch tube in mechanically ventilated patients with post
      resection bronchopleural fistula allows the anaesthesiologist to suction
      separately the two lungs and to ventilate adequately the remaining lung tissue,
      thus obtaining the lung reexpansion and the consequent reduction of the residual
      pleural space, and facilitating the healing of the fistula.

PMID- 15939618
TI  - Surgery for acute type A aortic dissection in pregnant patients with Marfan
      syndrome.
AB  - OBJECTIVE: Acute type A aortic dissection during pregnancy can be fatal to both
      the mother and the fetus. The goal of the present study was to characterize the
      prevalence, treatment and outcomes of this dangerous condition in an effort to
      determine optimal management. METHODS: A retrospective study was conducted using
      data from four Marfan patients with acute type A aortic dissection during
      pregnancy at our institution between 1991 and 2003. RESULTS: The mean gestational
      period at the time of operative repair was 31 weeks, with a range of 26-34 weeks,
      and the aortic root diameter ranged from 35 to 85 mm. Two of the four patients
      underwent a combined operation with cesarean section followed by aortic repair.
      One patient underwent operative aortic repair following spontaneous delivery. The
      final patient underwent aortic repair with the fetus remaining in situ. Median
      sternotomy and cardiopulmonary bypass were established via the femoral artery
      with direct right atria drainage and left atrial venting in all patients.
      Composite graft replacement combined with re-implantation of the coronary artery
      and aortic valve replacement were performed in three patients, and aortic valve
      replacement with coronary artery bypass grafting of the right coronary artery was
      performed in one patient. Three of four patients underwent aortic arch repair
      utilizing antegrade cerebral perfusion and deep hypothermia with total
      circulatory arrest. The patient that underwent operative correction with the
      fetus remaining in situ experienced fetal demise with miscarriage just after
      cardiac surgery, and the patient died 4 days later secondary to disseminated
      intravascular coagulation and multi-organ failure. The remaining three cases
      recovered uneventfully, and the mothers and babies were discharged in good
      condition. CONCLUSIONS: Based on these data, we advocate cesarean section with
      concomitant aortic repair for patients with Marfan syndrome and acute type A
      aortic dissection during pregnancy. Minimization of deep hypothermic circulatory
      arrest time is also recommended for cases in which the fetus remains in situ.

PMID- 15939619
TI  - Metabolic alkalosis after pediatric cardiac surgery.
AB  - OBJECTIVE: To determine occurrence, causes and associated mortality of
      postoperative metabolic alkalosis in pediatric cardiac surgery. METHODS: We
      retrospectively analyzed clinical and biochemical variables of 186 consecutive
      cardiac operations other than ductal ligations on children less than 2 years old
      during the years 1999 and 2000. Metabolic alkalosis was defined as a pH>7.48
      corrected for PCO2, with a base excess > or =5 on two or more consecutive
      measurements during an 8h period. RESULTS: Median age was 15 weeks [range 2 days
      95 weeks] and median weight 4.5 kg [range 2.1-15.7 kg]. In 157 cases,
      cardiopulmonary bypass was used. In 92 [49%] procedures, metabolic alkalosis
      occurred with the highest corrected pH 24.3h after operation. Multivariate
      regression analysis associated age [P<0.001], cardiopulmonary bypass [P<0.001]
      and preoperative ductal dependency [P=0.04] with postoperative metabolic
      alkalosis. Of the surgical procedures the arterial switch for transposition of
      the great arteries [n=19] was strongly associated with metabolic alkalosis [100%,
      P<0.001]. Hemodilution appeared to enhance the development of alkalosis: those
      who experienced alkalosis had been hemodiluted to a greater extent [P=0.007].
      Nearly 95% of patients experienced some increase in bicarbonate, but patients
      with metabolic alkalosis experienced more than those without [5.9 versus 3.5
      mmol/l, P<0.001]. There were four postoperative deaths, only one coincidental
      with metabolic alkalosis. CONCLUSIONS: Metabolic alkalosis has a high incidence
      after pediatric cardiac surgery, strongly associated with younger age,
      cardiopulmonary bypass, preoperative ductal dependency and perioperative
      hemodilution. Early recognition allows for timely therapeutic intervention.

PMID- 15939621
TI  - Comparison of minimally invasive closed circuit extracorporeal circulation with
      conventional cardiopulmonary bypass and with off-pump technique in CABG patients:
      selected parameters of coagulation and inflammatory system.
AB  - OBJECTIVE: Closed circuit extracorporeal circulation (CCECC) has been developed
      to reduce deleterious effects of standard cardiopulmonary bypass (CPB). This
      study compares the effects of CCECC (CORx system), CPB, and off-pump coronary
      artery bypass grafting (OPCAB) on red blood cell damage, coagulation activation,
      fibrinolysis and cytokine expression. METHODS: Thirty patients underwent coronary
      artery bypass grafting (CABG). Twenty of them were randomized into two groups:
      CCECC (n = 10), CPB (n = 10). While not randomized, OPCAB (n = 10) served as a
      separate reference group. CCECC and CPB patients received cardioplegic arrest.
      Interleukin 6 (IL-6), free hemoglobin (fHb), von Willebrand factor activity
      (vWf), thrombin-antithrombin-III-complex (TATc), prothrombin fragment 1.2 (F 1+2)
      and plasmin-antiplasmin complex (PAPc) were assessed preoperatively,
      perioperatively and 24 h postoperatively. RESULTS: CCECC showed significantly
      lower red blood cell damage than CPB (fHb: CCECC, 7.1+/- 5.7 micromol/l; CPB,
      16.8+/-11.4 micromol/l; P = 0.025; OPCAB, 3.4+/-1.1 micromol/l). Perioperatively,
      CCECC exhibited significantly lower activation of coagulation and fibrinolysis
      than CPB, but did not differ from OPCAB (vWf: CCECC, 133+/-52%; CPB, 241+/-128%;
      P = 0.052; OPCAB, 153+/-58%; TATc: CCECC, 4.7+/-0.9 ng/ml; CPB, 31.1+/-15.8
      ng/ml; P < 0.001; OPCAB, 2.4+/-0.6 ng/ml; PAPc: CCECC, 214+/-30 ng/ml; CPB, 897+/
      367 ng/ml; P < 0.001; OPCAB, 253+/-98 ng/ml). In contrast, fibrinolysis markers
      and IL-6 were markedly increased in CCECC postoperatively (PAPc: CCECC, 458+/-98
      ng/ml; CPB, 159+/-128 ng/ml; P < 0.001; OPCAB, 262+/-174 ng/ml; IL-6: CCECC,
      123.4+/-49.8 pg/dl; CPB, 18.8+/-13.1 pg/dl; P < 0.001; OPCAB, 31.6+/-26.2 pg/dl).
      CONCLUSIONS: CCECC for CABG is associated with a significant reduction of red
      blood cell damage and activation of coagulation cascades similar to OPCAB when
      compared with conventional CPB while a delayed fibrinolytic and inflammatory
      activity was observed. These findings require further investigation to verify the
      promising concept of CCECC.

PMID- 15939622
TI  - COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen
      and meloxicam: an in vitro analysis.
AB  - We report on the inhibitory activity of the NSAIDs meloxicam, carprofen,
      phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro
      enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam
      and carprofen are more selective inhibitors of COX-2 than phenylbutazone and
      flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined.
      However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2
      selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower
      COX-2 selectivity than at IC50. We therefore propose that the selectivity of
      NSAIDs should be assessed at the 80% as well as 50% inhibition level.

PMID- 15939623
TI  - The role of nitric oxide on glutaminergic modulation of dopaminergic activation.
AB  - Biochemical studies have been demonstrated that N-methyl-D-aspartate (NMDA)
      evoked dopaminergic (DAergic) activation can be modulated by nitric oxide (NO)
      systems. Therefore, behavioral study was performed to characterize the role of NO
      on NMDA modulation of DAergic activation. It is well known that apomorphine
      induces climbing behaviors in mice by the activation of DAergic receptors. Our
      previous studies showed that NMDA receptor antagonists reduced apomorphine
      induced climbing behaviors. It was reported that nitric oxide synthase (NOS)
      inhibitors reduced the apomorphine-induced climbing behaviors. In this
      experiment, NO donor restored the apomorphine-induced climbing behavior, which
      was inhibited by NMDA receptor antagonist. NOS inhibitor inhibited the
      apomorphine-induced climbing behavior, which was enhanced by NMDA receptor
      agonist. These results suggest that DAergic activation is regulated by both NMDA
      receptors and NO systems, and NO in the down-stream of NMDA receptors play an
      important role on the glutaminergic NMDA modulation of DAergic function.

PMID- 15939624
TI  - Oct2 transcription factors in fish--a comparative genomic analysis.
AB  - The Oct2 transcription factor is important in driving expression of the IgH locus
      of the channel catfish, Ictalurus punctatus. Two isoforms, catfish Oct2alpha and
      Oct2beta, have been characterized at the level of expression and function, but
      little is known of the structure of the Oct2 gene in catfish. To gain insight
      into the diversity of Oct2 gene structure and expression in the teleost fish, a
      comparative genomic analysis of Oct2 was undertaken in the pufferfish (Fugu
      rubripes) and the zebrafish (Danio rerio). The orthologues of zebrafish and Fugu
      Oct2 were identified, and share with catfish Oct2 the expression of a limited
      number (two in zebrafish, three in Fugu) of isotypes produced by alternative
      pathways of RNA processing. The alternatively spliced variants of catfish Oct2
      showed a different pattern of exon use from those of Fugu and zebrafish. The
      analysis also identified a novel homologue of Oct2 in both zebrafish and Fugu.
      This homologue, termed Oct2x, shares similarities to both Oct1 and Oct2. A
      phylogenetic analysis of the relationships of Oct2x gave an unexpected result,
      with Oct2x occupying a position basal to the Oct gene families of both
      vertebrates and Drosophila.

PMID- 15939625
TI  - Cytotoxic activities of fish leucocytes.
AB  - Like mammalian leucocytes, white blood cells of fish are able to kill altered
      (e.g. virus-infected) and foreign (allogeneic or xenogeneic) cells. The existence
      of natural killer (NK)-like and specific cytotoxic cells in fish was first shown
      using allogeneic and xenogeneic effector/target cell systems. In addition to in
      vivo and ex vivo studies, very important contributions were made by in vitro
      analysis using a number of different long-term cytotoxic cell lines established
      from channel catfish. In mammals, specific cell-mediated cytotoxicity (CMC) as
      part of the adaptive immune response requires a number of key molecules expressed
      on effector leucocytes and target cells. CD8+ T lymphocytes kill infected cells
      only, if their antigen receptor (TCR) matches the MHC class I with bound peptide
      of the target cell. Expression patterns of the fish gene homologues for TCR, CD8
      and MHC class I, as well as related genes, are in agreement with similar
      function. Convenient systems for the analysis of specific CMC have only recently
      become available for fish with the combination of clonal fish with syngeneic or
      allogeneic but MHC class I matching cell lines. It was demonstrated that both, NK
      and cytotoxic T (Tc) cells are involved in the killing of virus infected MHC
      class I matching and mismatching target cells. Analysis of these lymphocyte
      subsets is only starting for fish. There is also evidence that the different
      viral proteins trigger different subsets of killer cells. This review further
      discusses findings on fish CMC with regard to temperature/seasons and ontogeny.

PMID- 15939626
TI  - The interferon system of teleost fish.
AB  - Interferons (IFNs) are secreted proteins, which induce vertebrate cells into an
      antiviral state. In mammals, three families of IFNs (type I IFN, type II IFN and
      IFN-lambda) can be distinguished on the basis of gene structure, protein
      structure and functional properties. Type I IFNs, which include IFN-alpha and IFN
      beta, are encoded by intron lacking genes and have a major role in the first line
      of defense against viruses. The human IFN-lambdas have similar biological
      properties as type I IFNs, but are encoded by intron containing genes. Type II
      IFN is identical to IFN-gamma, which is produced by T helper 1 cells in response
      to mitogens and antigens and has a key role in adaptive cell mediated immunity.
      IFNs, which show structural and functional properties similar to mammalian type I
      IFNs, have recently been cloned from Atlantic salmon, channel catfish,
      pufferfish, and zebrafish. Teleost fish appear to have at least two type I IFN
      genes. Phylogenetic sequence analysis shows that the fish type I IFNs form a
      group separated from the avian type I IFNs and the mammalian IFN-alpha, -beta and
      -lambda groups. Interestingly, the fish IFNs possess the same exon/intron
      structure as the IFN-lambdas, but show most sequence similarity to IFN-alpha.
      Recently, IFN-gamma genes have also been cloned from several fish species and
      shown to have the same exon/intron structure as mammalian IFN-gamma genes. The
      antiviral effect of mammalian type I IFN is exerted through binding to the IFN
      alpha/beta-receptor, which triggers signal transduction through the JAK-STAT
      signal transduction pathway resulting in expression of Mx and other antiviral
      proteins. Putative IFN receptor genes have been identified in pufferfish. Several
      interferon regulatory factors and members of the JAK-STAT pathway have also been
      identified in various fish species. Moreover, Mx and several other interferon
      stimulated genes have been cloned and studied in fish. Furthermore, antiviral
      activity of Mx protein from Atlantic salmon and Japanese flounder has recently
      been demonstrated.

PMID- 15939627
TI  - Ontogeny of the immune system of fish.
AB  - Information on the ontogeny of the fish immune system is largely restricted to a
      few species of teleosts (e.g., rainbow trout, catfish, zebrafish, sea bass) and
      has previously focused on morphological features. However, basic questions
      including the identification of the first lympho-hematopoietic sites, the origin
      of T- and B-lymphocytes and the acquisition of full immunological capacities
      remain to be resolved. We review these three main topics with special emphasis on
      recent results obtained from the zebrafish, a new experimental model particularly
      suitable for study of the ontogeny of the immune system because of its rapid
      development and easy manipulation. This species also provides an easy way of
      creating mutations that can be detected by various types of screens. In some
      teleosts (i.e., angelfish) the first blood cells are formed in the yolk sac. In
      others, such as zebrafish, the first hematopoietic site is an intraembryonic
      locus, the intermediate cell mass (ICM), whereas in both killifish and rainbow
      trout the first blood cells appear for a short time in the yolk sac but later the
      ICM becomes the main hematopoietic area. Erythrocytes and macrophages are the
      first blood cells to be identified in zebrafish embryos. They occur in the ICM,
      the duct of Cuvier and the peripheral circulation. Between 24 and 30 hour post
      fertilization (hpf) at a temperature of 28 degrees C a few myeloblasts and
      myelocytes appear between the yolk sac and the body walls, and the ventral region
      of the tail of 1-2 day-old zebrafish also contains developing blood cells. The
      thymus, kidney and spleen are the major lymphoid organs of teleosts. The thymus
      is the first organ to become lymphoid, although earlier the kidney can contain
      hematopoietic precursors but not lymphocytes. In freshwater, but not in marine,
      teleosts the spleen is the last organ to acquire that condition. We and other
      authors have demonstrated an early expression of Rag-1 in the zebrafish thymus
      that correlates well with the morphological identification of lymphoid cells. On
      the other hand, the origins and time of appearance of B lymphocytes in teleosts
      are a matter of discussion and recent results are summarized here. The
      functioning rather than the mere morphological evidence of lymphocytes determines
      when the full immunocompetence in fish is attained. Information on the
      histogenesis of fish lymphoid organs can also be obtained by analysing zebrafish
      mutants with defects in the development of immune progenitors and/or in the
      maturation of non-lymphoid stromal elements of the lymphoid organs. The main
      characteristics of some of these mutants will also be described.

PMID- 15939628
TI  - Evaluation of a method for bimanual testing coordination of hand grip and load
      forces under isometric conditions.
AB  - The purpose of the study was to evaluate a method for testing bimanual prehension
      based on a novel experimental device. The device consists of two handles allowing
      for simultaneous measurement of bimanual hand grip forces (GF) and different
      patterns of load forces (LF) exerted during compression and tension along the
      longitudinal axis. In order to assess the reliability of the obtained measures,
      eight healthy subjects were tested over three consecutive test, while three
      moderately impaired neurological patients were tested once. In healthy subjects,
      high coordination was observed between GFs and LFs, as well as between two GFs
      and two LFs. The results also suggest a satisfactory task performance in regards
      to exerting the instructed LF profile, as well as a sufficient, but not excessive
      GF. The reliability of most of the assessed variables proved to be either
      moderate or high. When compared to healthy subjects, the data obtained from
      neurological patients mainly revealed irregular patterns of LFs, excessive GFs,
      as well as a relatively weak relationship between GFs and LFs. It was concluded
      that the evaluated methodological approach can be applied not only to explore uni
      and bi-manual coordination of arm and hand grip forces in various prehensile
      activities, but also to serve as a basis for future development of specific
      clinical tests for neurological patients and other populations that demonstrate
      impaired hand function.

PMID- 15939629
TI  - Long-term repeatability of force, endurance time and muscle activity during
      isometric contractions.
AB  - We determined the repeatability and correlations between force, endurance and
      muscle activity during isometric contractions over three years. Twenty-six
      subjects, with and without complaints of the shoulder and neck, performed
      standardized maximal and submaximal shoulder-abduction contractions and wrist
      extension-contractions at yearly intervals from 1997 to 1999. Peak forces
      developed during maximal contraction and the endurance times of submaximal
      contractions during shoulder abduction and wrist extension were measured.
      Electromyography (EMG) of muscle activity was recorded bilaterally from the upper
      trapezius, middle deltoid, and forearm extensor muscles. Root mean square EMG
      amplitudes were calculated. We found statistically significant associations
      between peak forces developed during wrist extension and shoulder abduction, and
      between endurance times of submaximal wrist extension and shoulder abduction. No
      statistically significant changes in peak force and EMG(peak) were found over the
      measurement years. The responses were not statistically significantly influenced
      by gender, or neck and shoulder pain. However, we observed considerable intra
      individual variation in the inter-year measurements particularly for the
      responses to submaximal contraction. Such large variations represent a challenge
      when attempting to use the responses to interpret the effects of therapies.

PMID- 15939630
TI  - Nuclear ribosomal DNA sequence variation and evolution of spotted marsh-orchids
      (Dactylorhiza maculata group).
AB  - Sequences of both internal and external transcribed spacers of nuclear ribosomal
      DNA were sequenced for four species belonging to the Dactylorhiza maculata group
      or "spotted marsh-Orchids". These four species are D. fuchsii, D. saccifera, D.
      foliosa, and D. maculata. Extensive nuclear ribosomal DNA polymorphism was
      uncovered within the diploid D. fuchsii and the putative autotetraploid D.
      maculata. Within the phylogenetic trees reconstructed using parsimony and
      Bayesian analyses, four main lineages (A, B, C, and D) were well supported. While
      D. saccifera, D. maculata, and D. foliosa were confined to clades B, C, and D,
      respectively, D. fuchsii accessions were spread over three clades (A, B, and C).
      Lineage C, which included accessions of the diploid D. fuchsii and the tetraploid
      D. maculata, was closely related to the lineage of D. foliosa (lineage D), an
      endemic diploid species from Madeira. Moreover, intra-individual polymorphism was
      found within accessions of D. maculata, D. fuchsii, and D. saccifera. It is shown
      that in some instances two lineages, contributed to the observed intra-individual
      polymorphism (C and A in D. maculata, A and B in D. fuchsii and D. saccifera).
      Evolutionary scenarios leading to this extensive nuclear ribosomal DNA
      polymorphism are discussed in the light of results from maternally inherited
      chloroplast DNA markers and an autopolyploid origin of D. maculata from a D.
      foliosa-like ancestor is postulated.

PMID- 15939631
TI  - Visual function in epilepsy patients treated with initial valproate monotherapy.
AB  - PURPOSE: To investigate whether initial valproate (VPA) monotherapy for the
      treatment of epilepsy causes visual field defects and visual dysfunction.
      METHODS: In a cross-sectional study, visual fields were examined with the kinetic
      Goldmann and automated Humphrey perimeters, contrast sensitivity function with
      the Pelli-Robson letter chart and colour vision with the Standard
      Pseudoisochromatic Plates Part 2 (SPP 2) and Farnsworth-Munsell 100 Hue test (FM
      100) in eighteen epilepsy patients (aged 18--50 years, 30.2.+/-10 years, mean+/
      S.D.) treated with initial valproate monotherapy for 2--20 years (8.4+/-5.1
      years). RESULTS: None had vigabatrin-type, concentric visual field defect with
      the kinetic Goldmann or automated Humphrey perimetries. In the Humphrey
      perimetry, the mean deviation for the group was within normal limits varying from
      -2.53 to 0.59 dB (-0.74+/-0.80 dB) in the right eye and from -2.66 to 0.67 dB (
      0.78+/-0.82 dB) in the left eye. In the FM 100 test, acquired colour vision
      deficiency was found in two out of 18 patients (11%, 95% CI: 0--25%). However,
      the mean total error score was lower in the patient group than in the control
      group. All patients had normal contrast sensitivity function. CONCLUSIONS: The
      use of VPA in the treatment of epilepsy is not associated with visual field
      defects similar to vigabatrin, but may induce abnormalities in colour vision.

PMID- 15939632
TI  - Gene transfection and expression in a primary culture of mammary epithelial cells
      isolated from lactating sows.
AB  - Porcine mammary epithelial cells (PMECs) were isolated from lactating sow mammary
      glands and cultured on a matrix gel. Primary culture cells expressed significant
      amounts of the specific marker cytokeratin as determined by immunohistochemistry,
      and exhibited mammary-specific functions, such as transcription of alpha
      lactalbumin, beta-casein and beta-lactoglobulin genes. They also formed
      mammospheres when the medium was supplemented with lactogenic hormones. The PMECs
      were used to study gene transfer and expression in vitro. A gene encoding
      enhanced green fluorescent protein (EGFP) was used as a reporter and two
      constructs were investigated, pEGFP-N1 (a vector constructed with a CMV promoter
      followed by the EGFP gene) and pGB562/GFP (a mammary gland-specific expression
      vector with regulatory sequences from the goat beta-casein gene linked to EGFP).
      The efficiency of DNA transfer into the cultured PMECs was about 20-30%. GFP
      expression in the pGB562/GFP-transfected PMECs was markedly stimulated by
      prolactin supplements in the medium. The established PMECs maintained optimal
      gene expression from 1 to 20 passages and appeared to provide an efficient and
      convenient system for assessing the expression of transgenes containing mammary
      gland-specific promoters.

PMID- 15939633
TI  - Pathways to caspase activation.
AB  - Apoptosis or programmed cell death is an active form of cell death which is
      essential for tissue homeostasis. Many proteins are involved in the molecular
      signal transduction of apoptosis. The caspase enzymes, a family of specific
      cysteine proteases, play a central role in cell death machinery. In this review,
      we mainly discuss the current understanding of several pathways to activate
      caspases and some key proteins related to these pathways.

PMID- 15939634
TI  - JAK-STAT signaling pathway in pulmonary arterial smooth muscle cells is activated
      by hypoxia.
AB  - Pulmonary arterial smooth muscle cells (PASMC) were divided into a normoxic group
      (N), 2, 8 and 12 h hypoxic groups (H2, H8 and H12) and an AG490 plus 8 h hypoxic
      group (AG490). The expression of JAK1, JAK2, JAK3 and TYK2 mRNA was analyzed by
      reverse transcription-polymerase chain reaction (RT-PCR). STAT1 and STAT3 protein
      expressions were determined by Western blotting. The results showed that the
      levels of JAK1, JAK2 and JAK3 mRNA did not change significantly in the N group
      but were increased after 2 h exposure to hypoxia. JAK1, JAK2 and JAK3 mRNA
      expressions peaked at 8 h. It decreased at 12 h but remained above those in the N
      group. TYK2 mRNA was not found in either hypoxic or normal PASMC. The phospho
      STAT1 and -STAT3 protein levels increased after 2 h exposure to hypoxia. They
      were about 2.8 and 4.1 times the N group, respectively, after 8 h. They decreased
      at 12 h but remained above those in the N group. AG490 inhibited phospho-STAT3
      protein expression by about 25.5% at 8 h but did not block the expression of
      phospho-STAT1 protein. These findings suggest that hypoxia induces the expression
      of JAK1, JAK2, JAK3 and phospho-STAT1 and -STAT3 in PASMC. Hypoxia activates the
      JAKs-STATs signaling pathway, which may participate in the pathogenesis of
      hypoxic PASMC injury.

PMID- 15939635
TI  - The influence of subintimal angioplasty on level of amputation and limb salvage
      rates in lower limb critical ischaemia: a 15-year experience.
AB  - OBJECTIVES: The aim of this study is to assess the influence of subintimal
      angioplasty (SIA) on lower limb amputation rate and level in critically ischaemic
      limbs. METHODS: Between January 1989 and March 2004, 1268 patients were admitted
      for treatment of lower limb critical ischaemia. Eight hundred and twenty-nine
      patients underwent revascularisation (bypass 671 and angioplasty 158), while 439
      patients had primary amputations. A retrospective analysis of a prospectively
      maintained vascular registry was performed. Patients were divided into two
      groups, those who were admitted prior to the availability of subintimal
      angioplasty and those treated post-introduction of angioplasty. The two groups
      were compared with regards to age, sex, diabetes mellitus, ASA grade, Rutherford
      classification and level of disease. Outcome was assessed by the limb salvage
      rate, 30-day morbidity and mortality, and length of hospital stay. RESULTS: The
      average number of revascularisation increased with the introduction of subintimal
      angioplasty, from 53 to 96 per year (p<0.001). The overall limb salvage rate
      increased significantly from 42 to 70% (p<0.001). The cumulative limb salvage
      rate following revascularisation rose from 72 to 86% (p<0.001). The level of
      amputation (AKA:BKA) did not vary significantly. Thirty-day morbidity, mortality
      and length of hospital stay were significantly lower in the post-angioplasty
      group. CONCLUSIONS: Technical advances have resulted in a steadying of amputation
      numbers despite an ageing population.

PMID- 15939636
TI  - Endovascular management of isolated infrarenal aortic occlusive disease is safe
      and effective in selected patients.
AB  - OBJECTIVE: To examine the safety and efficacy of endovascular management of
      isolated infrarenal aortic occlusive disease within our centre. DESIGN AND
      METHODS: Retrospective analysis of all patients who underwent endovascular
      treatment of occlusive disease that is confined to the infrarenal aorta between
      September 1993 and November 2004. RESULTS: Primary aortic stenting was carried
      out in 16 women and five men using self-expanding (12 patients) and balloon
      expanding stents to treat both occlusions (six) and stenoses (15). Indications
      included intermittent claudication (13), critical limb ischaemia (six), and
      distal embolisation (three). Significant postoperative complications within 30
      days were noted in three, including one death. Fifteen patients completed 1-year
      follow-up with primary patency in 14 and secondary patency in the remaining
      patient. Clinical improvement was documented in all patients. CONCLUSION: Primary
      stenting for occlusive disease isolated in the infrarenal aorta is relatively
      safe in selected patients with encouraging early follow-up results.

PMID- 15939637
TI  - The isolated internal iliac artery aneurysm--a review.
AB  - BACKGROUND: The isolated internal iliac artery aneurysm (IIIAA) is rare but
      rupture has a high mortality rate. This paper reviews the available literature
      regarding the epidemiology, aetiology, natural history, diagnosis and management
      with a focus on aneurysms of atherosclerotic origin. METHODS: A literature search
      was performed using internet databases PubMed, Medline and Medscape followed by
      manual cross referencing of relevant articles. Data were retrieved from the
      papers, tabulated and analysed to form a review of atherosclerotic IIIAA.
      RESULTS: Three hundred and seventy-two papers were found relating to internal
      iliac artery aneurysms in general and 82 were directly relevant to this paper,
      reporting 94 cases of atherosclerotic IIIAA. For atherosclerotic aneurysms, the
      median (range) age was 71.9 (47-89) years and 95% were male. The natural history
      is unclear but is probably one of increasing size, with corresponding increased
      risk of rupture. Presentation was with rupture in 40%, leading to rapid death if
      untreated. The death rate in the group as a whole was 31%. The median (range)
      size of aneurysms at diagnosis was 7.7 (2-13) cm and death was significantly
      associated with rupture (Spearman correlation coefficient r=0.327, p=0.007).
      Symptoms included abdominal pain (31.7%), urological symptoms (28.3%),
      neurological symptoms (18.3%), groin pain (11.7%), hip or buttock pain (8.3%) and
      gastrointestinal symptoms (8.3%). Diagnosis may also be coincidental as a result
      of investigation for other conditions. Of particular use in diagnosis and
      assessment are ultrasound, computerised tomography and magnetic resonance
      angiography. Surgical treatment is difficult but can be achieved by ligation,
      excision or endoanneurysmorrhaphy. More recently, radiological treatments include
      coil embolisation and endoluminal stenting (often in combination) with the
      established advantages of endovascular repair have yielded promising short term
      results, although long term follow-up is required to assess complications and the
      durability of the devices. CONCLUSIONS: Atherosclerotic IIIAA is a rare condition
      and if undiagnosed is often fatal. Early diagnosis and treatment may reduce
      morbidity and mortality particularly with the advent of endovascular techniques.

PMID- 15939638
TI  - Urinary albumin:creatinine ratio (ACR) and the prediction of postoperative
      complications after abdominal aortic aneurysm repair.
AB  - INTRODUCTION: Open repair of abdominal aortic aneurysm (AAA) requires aortic
      clamping. This results in an ischaemia-reperfusion injury (IRI) which can lead to
      the development of the systemic inflammatory response syndrome (SIRS) and
      multiple organ failure (MOF). We investigated the use of urinary
      albumin:creatinine ratio (ACR) as a simple predictor of the development of
      complications (SIRS) postoperatively. METHODS: Forty-four patients undergoing
      elective infrarenal AAA repair and 10 control patients undergoing major abdominal
      surgery had fresh urine samples taken before, immediately after and 24 h after
      the procedure. Urinary ACR was calculated on all samples, and daily SIRS scores
      were calculated for all patients postoperatively. Systemic interleukin-6 (IL-6)
      levels were measured intraoperatively to measure the cytokine response to
      surgery. RESULTS: AAA patients demonstrated a characteristic pattern of ACR
      levels during the three time points, with a significant increase in the ACR
      immediately postoperatively and with normalisation by 24 h (P<0.001 Wilcoxon
      signed ranks test). In comparison, control patients did not demonstrate any
      changes in their ACR (P=0.45 Wilcoxon signed ranks test) suggesting the increased
      ACR in AAA patients to occur as a result of IRI. ACR did not correlate with the
      development of SIRS postoperatively or with the systemic IL-6 response.
      CONCLUSIONS: Infrarenal AAA repair is associated with a temporary and reversible
      renal injury. ACR could not, however, be used as a predictor of complications
      postoperatively.

PMID- 15939639
TI  - Epidemiological clues to preventing colic.
AB  - Colic remains a significant problem in the horse in terms of welfare and
      economics; in some equine populations it is the single most common cause of
      death. Many causes of colic are cited in the equestrian and veterinary literature
      but little scientific evidence exists to substantiate these theories. Recent
      epidemiological investigations have confirmed that colic is complex and multi
      factorial in nature. Studies have identified a number of factors that are
      associated with increased risk of colic including parasite burden, certain feed
      types, recent change in feeding practices, stabling, lack of access to pasture
      and water, increasing exercise and transport. These findings are reviewed
      together with examples of management practices that may be altered to reduce the
      incidence of specific types of colic. This is an opinionated, not a systematic,
      review focusing on those areas that are considered most relevant to the
      practitioner.

PMID- 15939640
TI  - Magnetic material in head, thorax, and abdomen of Solenopsis substituta ants: a
      ferromagnetic resonance study.
AB  - Ferromagnetic resonance temperature dependence is used to study the magnetic
      material in smashed head, thorax, and abdomen of Solenopsis substituta ants.
      These three body parts present the five lines previously observed in other social
      insects. The magnetic material content is slightly higher in heads with antennae
      than in abdomen with petiole. Isolated nanoparticle diameters were estimated as
      12.5 +/- 0.1 and 11.0 +/- 0.2 nm in abdomen with petiole and head with antennae,
      respectively. The presence of linear chains of these particles or large
      ellipsoidal particles are suggested. A bulk-like magnetite particle was observed
      in the thorax. The Curie-Weiss, the structural-electronic and ordering transition
      temperatures were obtained in good agreement with those proposed for magnetite
      nanoparticles.

PMID- 15939641
TI  - The internal magnetic field distribution, and single exponential magnetic
      resonance free induction decay, in rocks.
AB  - When fluid saturated porous media are subjected to an applied uniform magnetic
      field, an internal magnetic field, inside the pore space, is induced due to
      magnetic susceptibility differences between the pore-filling fluid and the solid
      matrix. The microscopic distribution of the internal magnetic field, and its
      gradients, was simulated based on the thin-section pore structure of a
      sedimentary rock. The simulation results were verified experimentally. We show
      that the 'decay due to diffusion in internal field' magnetic resonance technique
      may be applied to measure the pore size distribution in partially saturated
      porous media. For the first time, we have observed that the internal magnetic
      field and its gradients in porous rocks have a Lorentzian distribution, with an
      average gradient value of zero. The Lorentzian distribution of internal magnetic
      field arises from the large susceptibility contrast and an intrinsic disordered
      pore structure in these porous media. We confirm that the single exponential
      magnetic resonance free induction decay commonly observed in fluid saturated
      porous media arises from a Lorentzian internal field distribution. A linear
      relationship between the magnetic resonance linewidth, and the product of the
      susceptibility difference in the porous media and the applied magnetic field, is
      observed through simulation and experiment.

PMID- 15939642
TI  - Planar microresonators for EPR experiments.
AB  - EPR resonators on the basis of standing-wave cavities are optimised for large
      samples. For small samples it is possible to design different resonators that
      have much better power handling properties and higher sensitivity. Other
      parameters being equal, the sensitivity of the resonator can be increased by
      minimising its size and thus increasing the filling factor. Like in NMR, it is
      possible to use lumped elements; coils can confine the microwave field to volumes
      that are much smaller than the wavelength. We discuss the design and evaluation
      of EPR resonators on the basis of planar microcoils. Our test resonators, which
      operate at a frequency of 14 GHz, have excellent microwave efficiency factors,
      achieving 24 ns pi/2 EPR pulses with an input power of 17 mW. The sensitivity
      tests with DPPH samples resulted in the sensitivity value 2.3 x 10(9) spins.G(-1)
      Hz(-1/2) at 300 K.

PMID- 15939643
TI  - Four differentially expressed cDNAs in Callinectes sapidus containing the Rebers
      Riddiford consensus sequence.
AB  - Decapod crustaceans such as Callinectes sapidus, the blue crab, provide unique
      opportunities to study proteins involved in biomineralization. Subsequent to each
      molt, the previously deposited soft cuticle is calcified while the postecdysial
      layers are simultaneously deposited and mineralized. Though the majority of the
      exoskeleton hardens, morphologically similar cuticle at the joints, called
      arthrodial membrane, remains flexible. It seems reasonable that hypodermal cells
      producing these cuticle types should be synthesizing proteins that regulate
      mineralization. Data presented here are consistent with this hypothesis, showing
      that transcripts coding for proteins containing the chitin-binding Rebers
      Riddiford (RR) consensus sequence (Gx(8)Gx(7)YxAxExGYx(7)Px(2)P) are
      differentially expressed. Two RR-containing transcripts, CsAMP8.1 and CsAMP6.0,
      are found only in arthrodial membrane and are expressed uniformly both before and
      after ecdysis. They have high sequence homology with RR-containing proteins from
      uncalcified portions of the cuticle of Cancer pagurus, Penaeus japonicus, and
      Homarus americanus. The other two transcripts, CsCP8.5 and CsCP8.2, are expressed
      solely in premolt and in hypodermis depositing calcifying cuticle rather than
      arthrodial membrane. They have high sequence homology with calcification
      associated peptides containing the RR sequence obtained from the calcified
      cuticle of Procambarus clarkii. This suggests possible involvement in the
      postmolt mineralization of the pre-ecdysial cuticle.

PMID- 15939644
TI  - Clinical, pathological, and biochemical studies in a patient with propionic
      acidemia and fatal cardiomyopathy.
AB  - A patient diagnosed at 9 months with a milder form of propionic acidemia was
      functioning at a near normal intellectual level and a normal neurological level
      at age 8. After 2-week history of feeling "poorly" but functioning normally, she
      became acutely ill and succumbed to heart failure and ventricular fibrillation in
      12 h. At post-mortem the heart was hypertrophied and had low carnitine levels,
      despite carnitine supplementation and repeatedly normal plasma carnitine levels.
      The findings in this patient provide a possible mechanism for the cardiac
      complications that are becoming more apparent in propionic acidemia.

PMID- 15939645
TI  - Gastrointestinal manifestations of Fabry disease: clinical response to enzyme
      replacement therapy.
AB  - Gastrointestinal symptoms are often an early and prominent manifestation of Fabry
      disease, an X-linked inborn error of metabolism caused by the deficient activity
      of the lysosomal enzyme, alpha-galactosidase A. This enzyme deficiency results in
      the progressive accumulation of globotriaosylceramide and other
      glycosphingolipids in tissue lysosomes throughout the body. In classically
      affected patients, glycosphingolipid accumulation in the vascular endothelium
      eventually culminates in life-threatening renal, cardiac, and cerebrovascular
      disease. In addition, over 50% of patients experience post-prandial abdominal
      pain and diarrhea that interferes with the ability to work and quality of life.
      Here, we describe four males aged 17-40 years with classic Fabry disease and
      severe gastrointestinal symptoms who participated in clinical trials of enzyme
      replacement therapy with agalsidase beta (Fabrazyme, 1 mg/kg every 2 weeks).
      Before therapy, the three adult patients experienced post-prandial abdominal
      pain, bloating, and severe diarrhea with 7-10 bowel movements per day every day
      and the 17-year-old had weekly episodes of diarrhea with six bowel movements per
      day. Other symptoms included vomiting, food intolerance, and poor weight gain.
      All patients took medications for these symptoms (diphenoxylate-atropine
      [Lomotil], ranitidine hydrochloride [Zantac], or sulfasalazine). After 6-7 months
      of agalsidase beta therapy, all patients reported "no or only occasional"
      abdominal pain or diarrhea, had discontinued their gastrointestinal medications,
      and had gained 3-8 kg. These marked improvements in gastrointestinal symptoms
      have persisted for over 3 years of treatment. In such patients, enzyme
      replacement at 1 mg/kg effects an early and significant clinical improvement in
      the gastrointestinal manifestations of Fabry disease.

PMID- 15939646
TI  - [Discussions about Europe].

PMID- 15939647
TI  - [Health research matters in the next ten years].

PMID- 15939648
TI  - [Tenth Anniversary of the National Blood Transfusion Institute, Monday 28th June
      2004. Presentation by Mr. Philippe Douste-Blasy, health and social welfare
      minister].

PMID- 15939649
TI  - [Blood transfusion in step with the European Union, the objectives of the
      Directive].

PMID- 15939650
TI  - [Public health and blood transfusion on a continental European scale].

PMID- 15939651
TI  - [Moving towards predictive and molecular medicine that is "reasonable and
      humane"].

PMID- 15939653
TI  - Identification, characterization and forensic application of novel Y-STRs.
AB  - Y-chromosomal polymorphic STRs are a powerful tool for forensic and evolutionary
      studies. Within the last decade, a series of Y-STR systems have been developed
      and demonstrated to be suitable for a variety of forensic applications including
      sexual assault cases and paternity testing. This review describes our recent
      studies on novel male-specific Y-STRs, involving identification, development of a
      multiplex-PCR system, population study and forensic application.

PMID- 15939654
TI  - Regulation of ABO gene expression.
AB  - The ABO blood group system is important in blood transfusions and in identifying
      individuals during criminal investigations. Two carbohydrate antigens, the A and
      B antigens, and their antibodies constitute this system. Although biochemical and
      molecular genetic studies have demonstrated the molecular basis of the histo
      blood group ABO system, some aspects remain to be elucidated. To explain the
      molecular basis of how the ABO genes are controlled in cell type-specific
      expression, during normal cell differentiation, and in cancer cells with invasive
      and metastatic potential that lack A/B antigens, it is essential to understand
      the regulatory mechanism of ABO gene transcription. We review the transcriptional
      regulation of the ABO gene, including positive and negative elements in the
      upstream region of the gene, and draw some inferences that help to explain the
      phenomena described above.

PMID- 15939655
TI  - Recent progress in mitochondrial DNA analysis.
AB  - In this review, we describe the current state of knowledge of mitochondrial
      genetics of East Asian populations and its application to forensic science.
      Recent advances in mitochondrial DNA (mtDNA) phylogeny have identified haplogroup
      specific single nucleotide polymorphisms (SNPs) and the control region motifs of
      haplogroups. By analyzing haplogroup-specific SNPs, we can rapidly and accurately
      connect the mtDNA under study to the relevant haplogroup. Haplogroups are fairly
      continent- and/or region-specific; therefore, we can infer the ethnic background
      of that mtDNA. In addition, errors in hypervariable region sequences can be
      detected by means of haplogroup motif analysis.

PMID- 15939656
TI  - Human tandem repeat sequences in forensic DNA typing.
AB  - It has been 20 years since the first development of DNA fingerprinting and the
      start of forensic DNA typing. Ever since, human tandem repeat DNA sequences have
      been the main targets for forensic DNA analysis. These repeat sequences are
      classified into minisatellites (or VNTRs) and microsatellites (or STRs). In this
      brief review, we discuss the historical and current forensic applications of such
      tandem repeats.

PMID- 15939657
TI  - Measurements of acoustic dispersion on calcaneus using spilt spectrum processing
      technique.
AB  - The speed of sound (SOS) has become a useful tool in osteoporosis assessment,
      since it represents a combination of density and compressibility of bone tissue
      and should provide better information on bone quality and an estimate the
      fracture risk. In general, the speed of sound on dispersive material, such as
      bone tissue, depends strongly on frequency. Therefore, a measurement of velocity
      dispersion magnitude (VDM) might provide more important bone structure
      information than measurements of bone mineral density (BMD), SOS or broadband
      ultrasound attenuation (BUA). To obtain the velocity dispersion magnitude
      requires a sequence of pulses that have a frequency that is different from that
      used in conventional approaches. The measurement is complicated by the fact that
      pulse waveform will distort as the pulses propagate through the frequency
      dependent medium. Alternatively, the phase velocity and velocity dispersion
      measurements also can be obtained on frequency-domain processing. However, the
      accuracy of those techniques is affected by the 2mpi ambiguity in the phase
      unwrapping process in frequency domain. And the spectrum approach is highly
      dependent on the gating window selection in time domain signals. The time-domain
      split spectrum processing (SSP) technique is proposed here to measure the phase
      velocity and the VDM. The SSP technique is also used to measure the SOS and VDM
      of two commercial calcaneus phantoms. Simulation results are in good agreement
      with the preset parameters of a model-based signal obtained using the SSP
      technique. In addition, in vitro SSP measurements agree with the manufacturer's
      specifications for two commercial calcaneus phantoms. The negative dispersion is
      also found in in vivo measurements on human heel. Finally, an approach based on
      the time domain SSP technique has potential clinical applications for
      osteoporosis diagnosis.

PMID- 15939658
TI  - QRS artifact elimination on full night sleep EEG.
AB  - Spectral analysis is now a standard procedure for analyzing the
      electroencephalograms (EEG) obtained by polysomnographic recordings. These
      numerical methods assume an artifact-free EEG since artifacts create spurious
      spectral components. Our aim was the development of a QRS artifact removal
      technique that might be applied to full night EEG with a minimal human
      intervention. This technique should handle one EEG channel, with or without use
      of one ECG channel. Variance minimization, independent component analysis (ICA),
      morphological filters (MF) have been implemented. Careful attention has been
      given to define the MF structuring element. The tests on artifact-simulated and
      real data were checked on the residual ECG spectral components present in the
      cleaned EEG. The best results are obtained by the MF when the structuring element
      is an artifact template defined either directly on the EEG or on the ICA ECG
      component. Further developments are required to identify and subtract the T-wave
      artifacts.

PMID- 15939659
TI  - Membrane properties of retinal stem cells/progenitors.
AB  - The membrane properties of cells help integrate extrinsic information relayed
      through growth factors, chemokines, extracellular matrix, gap junctions and
      neurotransmitters towards modulating cell-intrinsic properties, which in turn
      determine whether cells remain quiescent, proliferate, differentiate, establish
      contact with other cells or remove themselves by activating programmed cell
      death. This review highlights some of the membrane properties of early and late
      retinal stem cells/progenitors, which are likely to be helpful in the
      identification and enrichment of these cells and in understanding mechanisms
      underlying their maintenance and differentiation. Understanding of membrane
      properties of retinal stem cells/progenitors is essential for the successful
      formulation of approaches to treat retinal degeneration and diseases by cell
      therapy.

PMID- 15939660
TI  - Vacuolar processing enzyme: an executor of plant cell death.
AB  - Apoptotic cell death in animals is regulated by cysteine proteinases called
      caspases. Recently, vacuolar processing enzyme (VPE) was identified as a plant
      caspase. VPE deficiency prevents cell death during hypersensitive response and
      cell death of limited cell layers at the early stage of embryogenesis. Because
      plants do not have macrophages, dying cells must degrade their materials by
      themselves. VPE plays an essential role in the regulation of the lytic system of
      plants during the processes of defense and development. VPE is localized in the
      vacuoles, unlike animal caspases, which are localized in the cytosol. Thus,
      plants might have evolved a regulated cellular suicide strategy that, unlike
      animal apoptosis, is mediated by VPE and the vacuoles.

PMID- 15939661
TI  - The role of abscisic acid in plant-pathogen interactions.
AB  - The effect of the abiotic stress hormone abscisic acid on plant disease
      resistance is a neglected field of research. With few exceptions, abscisic acid
      has been considered a negative regulator of disease resistance. This negative
      effect appears to be due to the interference of abscisic acid with biotic stress
      signaling that is regulated by salicylic acid, jasmonic acid and ethylene, and to
      an additional effect of ABA on shared components of stress signaling. However,
      recent research shows that abscisic acid can also be implicated in increasing the
      resistance of plants towards pathogens via its positive effect on callose
      deposition.

PMID- 15939662
TI  - Functions of the respiratory burst oxidase in biotic interactions, abiotic stress
      and development.
AB  - The production of reactive oxygen intermediates (ROI) is among the earliest
      temporal events following pathogen recognition in plants. Initially, ROI were
      thought to be cell-death executioners. Emerging evidence, however, suggests a
      broader role for ROI as signals that mediate responses to infection, the abiotic
      environment, developmental cues, and programmed cell death in different cell
      types. The Respiratory burst oxidase homolog (Rboh) gene family encodes the key
      enzymatic subunit of the plant NADPH oxidase. Rboh proteins are the source of ROI
      produced following pathogen recognition and in a variety of other processes.

PMID- 15939663
TI  - The complex interplay between plant viruses and host RNA-silencing pathways.
AB  - RNA silencing was originally identified as an immune system targeted against
      transposons and viruses, but is now also recognized as a major regulatory process
      that affects all layers of host gene expression through the activities of various
      small RNA species. Recent work in plants and animals indicates that viruses not
      only suppress, but can also exploit, endogenous RNA silencing pathways to
      redirect host gene expression. There are also indications that cellular, as
      opposed to virus-derived small RNAs, might well constitute an unsuspected defense
      layer against foreign nucleic acids. This complex interplay has implications in
      the context of disease resistance and evolution of viral genomes.

PMID- 15939664
TI  - Plant immunity: the EDS1 regulatory node.
AB  - ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) and its interacting partner, PHYTOALEXIN
      DEFICIENT 4 (PAD4), constitute a regulatory hub that is essential for basal
      resistance to invasive biotrophic and hemi-biotrophic pathogens. EDS1 and PAD4
      are also recruited by Toll-Interleukin-1 receptor (TIR)-type nucleotide binding
      leucine rich repeat (NB-LRR) proteins to signal isolate-specific pathogen
      recognition. Recent work points to a fundamental role of EDS1 and PAD4 in
      transducing redox signals in response to certain biotic and abiotic stresses.
      These intracellular proteins are important activators of salicylic acid (SA)
      signaling and also mediate antagonism between the jasmonic acid (JA) and ethylene
      (ET) defense response pathways. EDS1 forms several molecularly and spatially
      distinct complexes with PAD4 and a newly discovered in vivo signaling partner,
      SENESCENCE ASSOCIATED GENE 101 (SAG101). Together, EDS1, PAD4 and SAG101 provide
      a major barrier to infection by both host-adapted and non-host pathogens.

PMID- 15939665
TI  - Plant secondary metabolites and vertebrate herbivores--from physiological
      regulation to ecosystem function.
AB  - Plant secondary metabolites can constrain the diet of vertebrates and these
      effects can flow through to community dynamics. Recent studies have moved beyond
      attempting to correlate diet choice with secondary metabolite profiles and
      instead focus on mechanisms that animals use to detect toxins and to regulate
      their intake and absorption. These include molecularly determined taste
      specificity, serotonin-mediated learning and the control of toxin absorption by
      permeability-glycoproteins. Focus on the detoxification pathways employed by
      specialist and generalist herbivores has facilitated explicit tests of the long
      standing hypothesis that detoxification rates limit feeding. Understanding the
      molecular basis of differences amongst species in their tolerance of plant
      secondary metabolites opens many opportunities for understanding the evolutionary
      history of interactions between vertebrates and their food plants.

PMID- 15939666
TI  - Biotic interactions of mites, plants and leaf domatia.
AB  - Leaf domatia, minute structures that typically house mites and other small
      arthropods, are produced by an impressive number of plants; however, their role
      in mediating plant-mite mutualism has only recently been elucidated. New evidence
      indicates that domatia function primarily as refuges for beneficial mites against
      predators. The presence of domatia therefore results in more beneficial mites on
      leaves, fewer pathogen attacks and reduced leaf herbivory. Unexpectedly,
      herbivorous mites are specialized domatia inhabitants of some plants. By
      providing refuges for herbivores, however, domatia may stabilize interactions
      between predator and their mite prey and thereby reduce the chances of herbivore
      outbreaks. Understanding the ecological mechanisms that promote beneficial
      interactions between mites and plants could have important implications for pest
      management.

PMID- 15939667
TI  - Systemic signaling in the wound response.
AB  - In many plants, localized tissue damage elicits an array of systemic defense
      responses against herbivore attack. Progress in our understanding of the long
      distance signaling events that control these responses has been aided by the
      identification of mutants that fail to mount systemic defenses in response to
      wounding. Grafting experiments conducted with various mutants of tomato indicate
      that systemic signaling requires both the biosynthesis of jasmonic acid at the
      site of wounding and the ability to perceive a jasmonate signal in remote
      tissues. These and other studies support the hypothesis that jasmonic acid
      regulates the production of, or acts as, a mobile wound signal. Following its
      synthesis in peroxisomes, further metabolism of jasmonic acid might enhance its
      stability, transport, or action in remote tissues. Recent studies in tomato
      suggest that the peptide signal systemin promotes long-distance defense responses
      by amplifying jasmonate production in vascular tissues.

PMID- 15939668
TI  - Gpi17p does not stably interact with other subunits of
      glycosylphosphatidylinositol transamidase in Saccharomyces cerevisiae.
AB  - Homologues of Gpi8p, Gaa1p, Gpi16p, Gpi17p, and Cdc91p are essential components
      of the GPI transamidase complex that adds glycosylphosphatidylinositols (GPIs 1)
      to newly synthesized proteins in the ER. In mammalian cells, these five subunits
      remain stably associated with each other in detergent. In yeast, we find no
      stable stoichiometric association of Gpi17p with the Gpi8p-Gpi16p-Gaa1p core in
      detergent extracts. Random and site-directed mutagenesis generated mutations in
      several highly conserved amino acids but did not yield nonfunctional alleles of
      Gpi17p and a saturating screen did not yield any dominant negative alleles of
      Gpi17p. Moreover, Gpi8p becomes unstable when any one of the other subunits is
      depleted, whereas Gpi17p is slightly affected only by the depletion of Gaa1p.
      These data suggest that yeast Gpi17p may be able to exert its GPI anchoring
      function without interacting in a stable and continuous manner with the other GPI
      transamidase subunits. Shutting down ER-associated and vacuolar protein
      degradation pathways has no effect on the levels of Gpi17p or other transamidase
      subunits.

PMID- 15939669
TI  - Soluble T cell receptors: novel immunotherapies.
AB  - T cell receptors are antigen-specific proteins that have evolved to recognize
      peptide antigens presented by human leukocyte antigen molecules on most cell
      types. Like antibodies, T cell receptors are produced with huge diversity but,
      unlike antibodies, T cell receptors are not secreted and do not undergo somatic
      mutations that increase their affinities for antigen. Recently, however, methods
      have been developed that enable T cell receptors to be engineered as soluble
      proteins with extremely high affinities, and fused to various immune-modulator
      molecules. T cell receptors are now set to unlock a whole new range of targets
      with key roles in cancer, viral infections, autoimmune diseases and allergies.

PMID- 15939670
TI  - Induction of donor-specific tolerance in sublethally irradiated recipients by
      gene therapy.
AB  - Donor-specific transplantation tolerance can be established through the induction
      of molecular chimerism following reconstitution of lethally irradiated mice with
      autologous bone marrow expressing retrovirally transduced allogeneic MHC
      antigens. Here, we set out to define nonmyeloablative host conditioning regimens
      that would allow for establishment of molecular chimerism and the induction of
      donor-specific tolerance. Recipient mice received various doses of whole-body
      irradiation, together with costimulatory blockade using anti-CD154 monoclonal
      antibody prior to reconstitution with syngeneic bone marrow cells transduced with
      retroviruses carrying the gene encoding H-2K(b). Conditioning consisting of 3 Gy
      whole-body irradiation and treatment with anti-CD154 was sufficient to induce
      molecular chimerism resulting in stable multilineage expression of K(b) on
      hematopoietic cells. T cells from molecular chimeras were unable to lyse
      allogeneic targets expressing K(b) and contained substantially fewer K(b)
      reactive IL-2- and IFN-gamma-producing CD4 T cells than controls receiving mock
      transduced bone marrow. Induction of molecular chimerism using nonmyeloablative
      host conditioning allowed for permanent survival of K(b)-disparate allogeneic
      skin grafts. These data suggest that nonmyeloablative host conditioning can be
      used effectively to induce molecular chimerism resulting in transplantation
      tolerance.

PMID- 15939671
TI  - Left ventricular cavity area reflects N-terminal pro-brain natriuretic peptide
      plasma levels in heart failure.
AB  - AIMS: N-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in the
      diagnosis of heart failure (HF). LV two-dimensional cavity area from end-diastole
      (LVEDA) and end-systole (LVESA), and LV fractional area change (LVFAC) reflect
      changes in LV morphology and function without using geometric assumptions. In a
      multicenter study, we correlated LVEDA, LVESA and LVFAC with NT-proBNP, comparing
      patients with dilated and ischemic cardiomyopathy. METHODS AND RESULTS: We
      studied 106 HF patients. In the dilated group, NT-proBNP correlated with LVEDAI
      (r=0.6), LVESAI (r=0.7) and LVFAC (r=-0.6), all significant at p<0.001. In
      patients with ischemic cardiomyopathy we found LVESAI (r=0.3, p<0.05) and LVFAC
      (r=-0.4, p<0.01). After adjustment for age and BMI, LVFAC and LVESAI were
      associated in a multiple linear regression analysis with peptide levels (adjusted
      r(2)=0.5, p<0.001). CONCLUSIONS: In this study we found a good correlation of NT
      proBNP with LV cavity areas and LVFAC. Multiple regression analysis showed that
      when adjusted for age and BMI, LVFAC and LVESAI are independent predictors of NT
      proBNP levels in both dilated and ischemic etiologies. Patients with dilated
      cardiomyopathy showed better results than those with ischemic cardiomyopathy. We
      think LV areas are a useful and reproducible parameter, do not need geometric
      assumptions and reflect NT-proBNP plasma levels.

PMID- 15939672
TI  - The Brief Symptom Inventory (BSI) as a screening tool for psychological disorders
      in patients with epilepsy and mild intellectual disabilities in residential care.
AB  - This study examines the usefulness of the Brief Symptom Inventory (BSI) as a
      screening tool for psychological disorders in patients with epilepsy and mild
      intellectual disabilities. Participants were 91 residents of the Bethel
      Institute, Bielefeld, Germany. Cronbach's alpha was revealed to be sufficient for
      the composite score Global Severity Index (GSI) (0.95) and for most of the
      subscales (0.64-0.80). Compared with normative data, residents with epilepsy
      scored slightly higher on all BSI scales. Only the subscale Paranoid Ideation was
      especially elevated, a finding of heuristic value. Subgroups of residents with
      past psychiatric morbidity, on current psychotropic medication, with poor seizure
      control, and more epilepsy-related problems either tended toward or demonstrated
      higher GSI scores. These results indicate the validity of the questionnaire with
      the GSI as a global indicator of possible psychopathology. BSI subscales seemed
      to reflect predominantly the amount of emotional distress, but their potential to
      identify specific clinical syndromes remained unclear.

PMID- 15939673
TI  - Effect of comorbidities on medical care use and cost among refractory patients
      with partial seizure disorder.
AB  - PURPOSE: The goal of this work was to assess the effect of comorbidities on
      medical care use and costs among patients with partial seizure disorder who are
      also refractory to initial antiepileptic drug (AED) monotherapy. METHODS:
      Retrospective data from the PharMetrics managed care claims database were
      collected for adult patients treated with AED monotherapy between January 1, 2000
      and March 31, 2002. The associations of comorbidity, specifically the Charlson
      Comorbidity Index (CCI) and incidence of specific comorbid conditions, with total
      costs and with hospitalization were analyzed via econometric analysis and
      logistic regression. RESULTS: Five hundred forty-nine patients were identified
      and analyzed. The odds of hospitalization were 3.7 times greater among patients
      with a CCI1, than for patients without comorbidities (OR=3.7, 95% CI=1.7-7.9),
      while treatment costs for all medical care were 136% higher (P<0.05). Depression
      had the largest marginal effect on costs and on the likelihood of
      hospitalization. CONCLUSIONS: For patients refractory to initial AED monotherapy,
      the presence of comorbidities, especially depression, is associated with a
      substantial increase in medical care use and costs.

PMID- 15939674
TI  - The effect of morphine in rat small mesenteric arteries.
AB  - We investigated the effect of morphine in phenylephrine (PE)- or KCl
      precontracted rat small mesenteric arteries. Morphine (10(-6)-10(-4) M)
      administration caused concentration-dependent relaxation responses in small
      mesenteric arteries precontracted by PE or KCl. Removal of endothelium did not
      significantly alter the relaxation responses to morphine. The relaxant responses
      to morphine were partially inhibited by pre-treatment of tissues with naloxone
      (NAL, 10(-5) M) for 20 min. The inhibitory effect of NAL on relaxant responses to
      morphine in PE- or KCl-precontracted arteries did not differ significantly
      between endothelium-intact and endothelium-denuded preparations. Incubation of
      endothelium-intact or endothelium-denuded arterial segments with NOS inhibitor
      N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or cyclooxygenase (COX)
      inhibitor indomethacin (10(-5) M) or histamine H(1)-receptor blocker
      diphenhydramine (10(-6) M), for 20 min did not inhibit the relaxation responses
      to morphine. Small mesenteric arterial segment contractions induced by stepwise
      addition of calcium to high KCl solution with no calcium were almost completely
      inhibited by morphine. These findings suggested that morphine-induced relaxation
      responses in isolated rat small mesenteric arteries were neither dependent on
      endothelium nor blocked by NOS or COX inhibition but they rather seem to depend
      on an interaction of morphine with calcium influx pathways.

PMID- 15939675
TI  - Studies on the interaction of protein with acid chrome blue K by electrochemical
      method and its analytical application.
AB  - An electrochemical investigation on the interaction of acid chrome blue K (ACBK)
      with protein on the mercury electrode with different electrochemical methods such
      as cyclic voltammetry and linear sweep voltammetry was reported in this paper. In
      pH 3.0 Britton-Robinson (B-R) buffer solution, ACBK has an irreversible
      voltammetric reductive peak at -0.23 V (vs. SCE). The addition of human serum
      albumin (HSA) into the ACBK solution resulted in the decrease of reductive peak
      currents without the change of the peak potential and no new peaks appeared on
      the cyclic voltammogram. In the absence and presence of HSA, the electrochemical
      parameters such as the formal potential E0, the electrode reaction standard rate
      constant k(s) and the charge transfer coefficient alpha of the interaction system
      were calculated and the results showed that there were no significant changes
      between each other. Thus, the interaction of ACBK with protein forms an electro
      inactive supramolecular bio-complex, which induces the decrease of the free
      concentration of ACBK in the reaction solution, and the decrease of the reductive
      peak current of ACBK. The binding constant and the binding ratio are calculated
      as 1.29 x 10(8) and 1:2, respectively, and the interaction mechanism is
      discussed. Based on the binding reaction, this new electrochemical method is
      further applied to the determination of HSA with the linear range from 3.0-20.0
      mg/L and the linear regression equation as deltaIp"(nA) = 10.08 + 19.90 C (mg/L).
      This method was further applied to determinate the content of protein in the
      healthy human serum samples with the results in good agreement with the
      traditional Coomassie brilliant blue G-250 spectrophotometric method.

PMID- 15939677
TI  - Identification of the mass transfer mechanisms involved in the transport of human
      immunoglobulin-G in N,N,N',N'-ethylenediaminetetramethylenephosphonic acid
      modified zirconia.
AB  - Zirconia particles modified with N,N,N',N'
      ethylenediaminetetramethylenephosphonic acid (EDTPA), further referred to as
      r_PEZ, were studied as a support material for use in chromatography. Our previous
      studies have demonstrated the utility of r_PEZ in the separation of
      immunoglobulins from biological fluids. In the present study we sought to
      understand the underlying factors and identify the rate-limiting mechanisms that
      govern the transport of biomolecules in r_PEZ. Pulse injection techniques were
      used to elucidate the individual mass transfer parameters. Elution profiles
      obtained under retained and unretained conditions were approximated by the
      Gaussian equation and the corresponding HETP contributions were estimated. The
      dependence of the HETP values on incremental salt concentration in the mobile
      phase was determined. Resulting data in conjunction with the equations outlined
      in literature were used to estimate the theoretical number of transfer units for
      the chromatographic separation process. Our results indicate that surface
      diffusion probably plays a minor role; however pore diffusion was established to
      be the rate limiting mechanism for immunoglobulin G adsorption to r_PEZ. The HETP
      based methodology may be used to estimate the rate limiting mechanisms of mass
      transfer for any given chromatographic system under appropriate conditions.

PMID- 15939678
TI  - Simple sensitive and simultaneous high-performance liquid chromatography method
      of glucoconjugated and non-glucoconjugated porphyrins and chlorins using near
      infra-red fluorescence detection.
AB  - This paper reports, for the first time, a reversed-phase high performance liquid
      chromatographic method for the simultaneous determination of seven
      glucoconjugated and non-glucoconjugated porphyrins and chlorins, using near infra
      red fluorescence detection. Chromatographic separation was performed on nucleosil
      CN analytical column using an isocratic acetonitrile-0.1% (w/v) TFA at pH 1.8
      (55:45, v/v) as mobile phase. Wavelength gradient was employed for sensitive
      detection, porphyrins derivates were monitored at lambda(exc) = 440 nm and
      lambda(emi) = 680 nm; and chlorins derivates at lambda(exc) = 420 nm, lambda(emi)
      = 650 nm. The method was validated and applied to monitor the biodegradation of a
      tri glucoconjugated chlorin derivative, TPC(glu)3, in spiked samples of human
      serum.

PMID- 15939679
TI  - Femoral neck shape and the spatial distribution of its mineral mass varies with
      its size: Clinical and biomechanical implications.
AB  - The femoral neck (FN) is a cantilever with external and internal dimensions
      determining its size, shape, the spatial distribution of the mineralized cortical
      and trabecular bone tissue mass, and its strength. Geometric indices of FN
      strength are often derived using FN dimensions estimated in vivo from dual X-ray
      absorptiometry (DXA) assuming that the FN cross section approximates a circle or
      a square. As DXA does not measure FN depth, we examined whether circular, square,
      or elliptical models of FN cross sections predict FN depth, and so its external
      volume, shape, volumetric bone mineral density (vBMD), and geometric indices of
      strength. We studied paired FN specimens from 13 Caucasian female cadavers (mean
      age 69 years, range 29 to 85) using DXA, micro-computed tomography (mu-CT), and
      direct calliper measurements. DXA accurately measured FN width (supero-inferior
      diameter) but models assuming a circular and a square cross section overestimated
      FN depth (antero-posterior diameter) and volume, and so underestimated vBMD by
      15.0 +/- 5.8% (circular cross section) and by 33.2 +/- 4.6% (square cross
      section) (both P < 0.05). As depth was less than the width, an elliptical model
      with a constant depth/width ratio of 0.75 reduced the accuracy error in vBMD to
      14.0 +/- 8.5% (P = 0.10). However, as FN width increased, FN depth increased
      relatively less. An elliptical model using a quadratic equation to mimic this
      changing in shape with increasing size reduced the error in vBMD to 4.4 +/- 7.7%
      (NS). Circular cross-section models overestimated section modulus at the mid-FN
      by about 51%. The elliptical models reduced the error two- to three fold. Images
      from micro-CT scanning show that the FN cross-sectional shape resembles an
      ellipse with the long axis and the maximum moment of inertia (I(max)) oriented in
      the supero-inferior direction, and the cortical mass concentrated inferiorly. The
      larger the cross section, the more elliptical the shape, and the greater the
      I(max) supero-inferiorly, while I(min) (in the antero-posterior direction)
      remains relatively constant. The shape, spatial distribution of bone, and moments
      of inertia are likely to be adaptations to bending moments during bipedalism.
      Assuming the FN cross section approximates a circle or square produces errors in
      FN depth, volume, vBMD, and geometric indices of bone strength. Studies are
      needed to determine the effects of age, sex, and race on FN size and shape in
      health and disease.

PMID- 15939680
TI  - [Changes and renovations in AKD with some current surprises].

PMID- 15939681
TI  - Effects of glucose-insulin-potassium solution added to reperfusion treatment in
      acute myocardial infarction.
AB  - OBJECTIVE: Reperfusion treatment modalities used in the routine treatment
      protocols of acute myocardial infarction (AMI) were found to be ineffective in
      establishing the nutritional cellular reperfusion in the microvascular
      environment even they succeed to open the infarct related artery. Glucose-insulin
      potassium (GIK) solution, which is presumed to stimulate the glycolytic pathway,
      is experimentally proven to be the most efficacious substrate for the
      preservation of energy production and therefore the myocardial viability, in the
      setting of acute ischemia. METHODS: We compared, 54 patients who suffered AMI and
      received GIK solution (300 g glucose+50 IU crystallized insulin+80 mEq potassium
      chloride in one liter solution) in addition to conventional treatment (GIK group)
      with 27 patients who were traditionally treated (control group) for in-hospital
      and early-term (1 month) cardiac morbidity. We also compared the two groups in
      terms of heart rate variability (HRV). RESULTS: Eight patients in the control
      group developed new-onset symptomatic congestive heart failure whereas only 5
      patients in GIK group were found to have such a cardiac morbidity (p=0.01).
      Reduced HRV (<50 ms) was found in 3 patients of control group whereas no patient
      in GIK group had abnormal HRV (p=0.01). CONCLUSION: The GIK solution decreased
      the incidence of new-onset symptomatic congestive heart failure and low HRV after
      myocardial infarction. Larger multicenter trials need to resolve the questions on
      the efficiency of metabolic intervention with GIK solution in acute myocardial
      infarction.

PMID- 15939682
TI  - [Thrombotic, fibrinolytic and proliferative activities of pulmonary vascular bed
      in secondary pulmonary hypertension].
AB  - OBJECTIVE: To determine whether pulmonary vascular bed contributes to the
      development of in situ thrombosis and vascular remodelling in secondary pulmonary
      hypertension (SPH) via changes in its local secretory activities. METHODS:
      Seventy-one patients with the diagnosis of secondary pulmonary hypertension (38
      females, mean age 40.36+/-1.05 years) were included in the study. Selective right
      and left heart catheterization was performed to each patient for diagnostic
      purposes. Blood samples obtained from left ventricle (LV) and pulmonary artery
      (PA) of each patient were analyzed for levels of plasminogen activator inhibitor
      1 (PAI-1), platelet derived growth factor (PDGF), vascular endothelial growth
      factor (VEGF), D-dimer, von Willebrand factor (vWF), protein-C, antithrombin-III,
      fibrinogen, and plasminogen. Results were compared between LV and PA. Correlation
      analysis between each parameter and mean pulmonary artery pressure (MPAP) was
      performed. RESULTS: Although mean level of VEGF in LV and PA were found to be in
      normal range, it was significantly higher in LV than in PA (p<0.001). Mean PDGF
      and D-dimer levels, which remained in normal range were also higher in LV
      (p<0.001 and p<0.001, respectively) than in PA;.vWF showed similar degree of
      elevation in both LV and PA. Only one parameter, PAI-1, was found to be
      significantly higher in PA than in LV (p=0.012). Antithrombin-III, protein C,
      plasminogen, and fibrinogen levels showed no significant differences between two
      chambers. They also remained in normal range, except for fibrinogen, which was
      slightly elevated in both LV and PA. Correlation analysis revealed strong
      positive correlation between D-dimer level in both LV and PA and MPAP (r=0.775,
      p<0.001 and r=0.649, p<0.001, respectively). CONCLUSION: In SPH, pulmonary
      vascular bed shows increased thrombotic, hypofibrinolytic, and proliferative
      activities, which are partially related to the severity of illness.

PMID- 15939683
TI  - [Has the mortality rate from acute myocardial infarction fallen substantially in
      recent years? Single center data on elderly patient population].
AB  - OBJECTIVE: We aimed to compare the trend in clinical approach and interventions,
      in-hospital mortality rate in elderly patients with acute myocardial infarction
      (AMI) in a single reference center within subsequent years, 2000-2002. METHODS:
      In our retrospective analysis within years 2000 and 2003 we could reach 160
      eligible patients' data files, who were hospitalized for of AMI and aged above 70
      years. RESULTS: Within three years we evaluated data of 105 male and 55 female
      eligible patients (mean age: 74.0+/-3.3 years). In-hospital mortality was
      observed in 39 (24%) patients with a median admission-to-mortality time of 24
      hours. In 33 (20%) of the cases AMI involved more than one myocardial wall. Sixty
      one percent of the whole population and 80% of the patients with early in
      hospital mortality had reduced left ventricular ejection fraction. The comparison
      of treatment approaches within three years revealed a growing tendency for
      application of percutaneous transluminal coronary angioplasty (PTCA), surgical
      interventions and for the use of beta-blockers, angiotenzin converting enzyme
      inhibitors and lipid lowering agents (p<0.05). We did not observe any difference
      in mortality rates at subsequent years. CONCLUSION: In our single center analysis
      we observed changes in treatment policy in elderly AMI population, which was in
      concordance with the trends in international arena. But we were not able to show
      any reduction in mortality rate. Beyond the diverse ethnicity of our patient
      population, the relative delayed time to hospital admission, more extensive
      infarct area, lower administration of interventional procedures and primary PTCA,
      and most importantly the relative short time interval we analyzed may be
      contributing factors for still high in-hospital mortality in elderly population.

PMID- 15939684
TI  - The myocardial performance index in children with isolated left-to-right shunt
      lesions.
AB  - OBJECTIVE: The myocardial performance index (MPI) measures the ratio of
      isovolumic time intervals to ventricular ejection time. The effects of altered
      ventricular preload or afterload on MPI have yet to be determined. This study was
      designed to determine the impact of altered preload on left and right ventricular
      myocardial performance index in the clinical setting of left-to-right lesions.
      METHODS: The left and right ventricular myocardial performance indexes were
      measured in 17 patients with atrial septal defect (ages 6 to 148 months), 23
      patients with ventricular septal defect (ages 2 to 160 months), and 24 healthy
      children (ages 3 to 160 months). A complete 2- dimensional and Doppler
      echocardiographic examination was performed in all study groups. RESULTS: In
      patients with atrial septal defect, ventricular septal defect, and control group
      subjects, the left ventricular MPI was 0.38, 0.37 and 0.32, respectively, and the
      right ventricular MPI was 0.24, 0.21, and 0.20, respectively. No significant
      differences in the left and right ventricular myocardial performance indexes were
      seen between patients with left-to-right shunt lesions and control subjects.
      CONCLUSION: This study documents that the myocardial performance index is a
      quantitative measure of ventricular function that appears to be relatively
      independent of changes in preload.

PMID- 15939685
TI  - Cardiac troponin I elevation in paediatric cardiac catheterization.
AB  - OBJECTIVE: The aim of this study is to investigate prospectively whether
      intracardiac catheterization produces myocardial damage in paediatric heart.
      METHODS: The study was performed in all patients undergoing diagnostic cardiac
      catheterization at our institute. A baseline serum sample was drawn before the
      procedure. The second serum sample was obtained 4-6 hours after the procedure.
      Cardiac troponin-I and creatine kinase isoenzyme MB fraction levels were
      determined quantitatively. RESULTS: Diagnostic cardiac catheterization was
      performed in 30 patients. There were 17 males and 13 females in the study group.
      The median age was 12 months (range 1 to 204 months); the median body weight was
      8 kilograms (range 2.1 to 45 kilograms). The increase in cardiac troponin I
      (0.21+/-0.04 ng/ml to 1.16+/-1.40 ng/ml, p<0.05) and creatine kinase isoenzyme MB
      (26.68+/-7.53 U/L to 41.65+/-22.12 U/L, p< 0.05) levels after the procedure was
      significant. CONCLUSION: This study shows that serum elevations of cardiac
      troponin I and creatine kinase isoenzyme MB occur after the most of paediatric
      diagnostic cardiac catheterization procedures.

PMID- 15939686
TI  - [The effects of phase II cardiac rehabilitation programme on patients undergone
      coronary bypass surgery].
AB  - OBJECTIVE: To investigate the effects of phase II cardiac rehabilitation in 52
      patients undergone coronary artery bypass surgery. METHODS: Gradual walking
      tests, cardio-pulmonary capacity tests and lipid profile were administered to
      patients selected for phase II cardiac rehabilitation before and after the
      programme. Training was started on 12-channel electrocardiogram controlled
      running bands 3 times a week for 20 min periods for 12 weeks fitting the
      programme. Low or intermediate level exercise programme was applied to patients.
      Cleveland Clinic Chronotropic Assessment exercise protocol was used during
      rehabilitation. RESULTS: As a result of phase II cardiac rehabilitation
      administered to 52 patients undergone coronary bypass operation, exercise
      capacity, oxygen consumption, anaerobic threshold, cardiac output mean values
      (p<0.001) and mean HDL cholesterol level (p<0.05) were found to increase, whereas
      body mass index, total cholesterol, LDL cholesterol and triglyceride mean levels
      reduced (p<0.001) significantly. CONCLUSION: In patients who have undergone
      coronary bypass surgery, phase II cardiac rehabilitation is a very useful
      programme in improvement of life quality and secondary prevention.

PMID- 15939687
TI  - [Cardiac rehabilitation in our country].

PMID- 15939688
TI  - [Contrast media-induced nephropathy: clinical burden and current attempts for
      prevention].
AB  - Contrast media-induced nephropathy is the third most common cause of hospital
      acquired acute renal failure. With the increasing use of contrast media in
      diagnostic and interventional procedures it has become one of the major
      challenges encountered during routine cardiology practice. Despite clinical
      importance it is an under-recognized event with major morbidity and mortality.
      Risk of developing contrast media-induced nephropathy depends mainly on patients
      preexisting characteristics and physicochemical properties of the contrast agent.
      Primary attempts for the prevention of contrast media-induced nephropathy should
      include systematic review of patient's characteristics and risk stratification.
      Patients at the greatest risk for contrast media-induced nephropathy can be
      defined as those having preexisting impaired renal function, diabetes mellitus,
      and congestive heart failure. Other risk factors include; age above seventy
      years, female gender, dehydration and use of high volume contrast media. The more
      expeditious use of iso-osmolar non-ionic contrast media reduced the incidence of
      contrast media related renal dysfunction. Currently, the only widely proven
      method of reducing the risk of contrast-induced nephropathy is adequate pre and
      postprocedural hydration. In addition, prophylactic use of free radical scavenger
      N-acetylcysteine has been shown to prevent contrast media-induced nephropathy in
      some moderate-scale clinical trials and a meta-analysis. Despite the attempts to
      reduce the risk of contrast nephropathy, this clinical event affects over 25% of
      high risk patients and mortality remains to be high.

PMID- 15939689
TI  - [What we should not do in the catheterization laboratory].

PMID- 15939690
TI  - [Blood pressure control rates in hypertensive patients and their determining
      factors in two urban regions of Izmir].

PMID- 15939691
TI  - [Cardiac thrombus due to protein C deficiency].

PMID- 15939692
TI  - Left ventricular noncompaction with hypothyroidism and sensorineural hearing
      loss.

PMID- 15939693
TI  - Non-cardiac Tl-201 uptake on myocardial perfusion SPECT study.

PMID- 15939694
TI  - Annular insertion levels of atrioventricular valves along the interventricular
      septum alone can lead to misdiagnosis of ventricular morphology.

PMID- 15939695
TI  - Surgical removal of fractured guidewire with ministernotomy.

PMID- 15939696
TI  - Anabolic-androgenic steroids: a bad tenor for cardiovascular orchestra
      (Myocardial infarction with intracoronary thrombus induced by anabolic steroids).

PMID- 15939697
TI  - [A new philosophy on stem cell trials in cardiovascular diseases: to collect
      pollen or to be a beekeeper].

PMID- 15939698
TI  - Fetal echocardiography and postnatal electrocardiographies of omphalopagus twins.

PMID- 15939699
TI  - Isolated noncompaction of left ventricular myocardium in an elderly man.

PMID- 15939700
TI  - [Isolated left ventricular noncompaction: magnetic resonance imaging findings].

PMID- 15939701
TI  - Multiple vascular aneurysms in Behcet's disease.

PMID- 15939702
TI  - [A huge left atrial myxoma with angiographic tumour vascularity].

PMID- 15939703
TI  - Deletion of the datA site does not affect once-per-cell-cycle timing but induces
      rifampin-resistant replication.
AB  - In Escherichia coli, three mechanisms have been proposed to maintain proper
      regulation of replication so that initiation occurs once, and only once, per cell
      cycle. First, newly formed origins are inactivated by sequestration; second, the
      initiator, DnaA, is inactivated by the Hda protein at active replication forks;
      and third, the level of free DnaA protein is reduced by replication of the datA
      site. The datA site titrates unusually large amounts of DnaA and it has been
      reported that reinitiation, and thus asynchrony of replication, occurs in cells
      lacking this site. Here, we show that reinitiation in deltadatA cells does not
      occur during exponential growth and that an apparent asynchrony phenotype results
      from the occurrence of rifampin-resistant initiations. This shows that the datA
      site is not required to prevent reinitiation and limit initiation of replication
      to once per generation. The datA site may, however, play a role in timing of
      initiation relative to cell growth. Inactivation of active ATP-DnaA by the Hda
      protein and the sliding clamp of the polymerase was found to be required to
      prevent reinitiation and asynchrony of replication.

PMID- 15939704
TI  - A risk assessment perspective: application of mode of action and human relevance
      frameworks to the analysis of rodent tumor data.

PMID- 15939705
TI  - Effects of chronic alcohol treatment on acoustic startle reactivity during
      withdrawal and subsequent alcohol intake in high and low alcohol drinking rats.
AB  - AIMS: The purpose of the present study is to determine whether the inverse
      genetic association between alcohol withdrawal magnitude and genetic propensity
      for alcohol drinking that we have previously identified in alcohol-naive rats
      given alcohol acutely, would also be seen following chronic alcohol exposure. The
      effect of forced, chronic alcohol treatment on subsequent voluntary alcohol
      drinking was also examined. METHODS: Male rats from the high alcohol drinking
      (HAD2) and low alcohol drinking (LAD2) lines received two intragastric (IG)
      infusions of alcohol (3.0 g/kg BW; 25% v/v) or an equal volume of water,
      separated by 5 h, every day for 20 consecutive days (chronic alcohol treatment).
      Acoustic startle reactivity was assessed at 10, 14, and 18 h after the second
      infusion on days 1, 5, 10, 15, and 20. After acoustic startle testing was
      completed, all rats received two IG infusions of 3.0 g alcohol/kg BW, separated
      by 5 h, and blood alcohol content was assessed at 10, 14, and 18 h after the
      second alcohol infusion. All rats were then given a 24 h free-choice between
      alcohol and water for 8 weeks. RESULTS: Startle magnitude to a 120 dB tone was
      suppressed during alcohol withdrawal in both alcohol-treated HAD2 and LAD2 rats
      after 5, 10, and 15 days of alcohol treatment. Forced, chronic alcohol treatment
      produced metabolic tolerance in both the HAD2 and LAD2 lines and significantly
      suppressed subsequent voluntary alcohol intake in rats of the HAD2 line.
      CONCLUSIONS: Reduced acoustic startle reactivity during alcohol withdrawal in
      both HAD2 and LAD2 rats is consistent with our previous findings in the HAD2 but
      not the LAD2 line and may reflect reduced CNS excitability during withdrawal from
      forced alcohol exposure. Forced alcohol exposure robustly retarded the expression
      of a genetic predisposition toward alcohol drinking in rats selectively bred for
      high alcohol intake.

PMID- 15939706
TI  - A critical review of pharmacoeconomic studies of acamprosate.
AB  - AIMS: This review assessed the published data on the cost-effectiveness of
      acamprosate for the treatment of alcohol dependence. METHODS: Four Markov
      modelling studies have assessed the therapeutic benefit and economic impact of
      acamprosate on the treatment of alcohol dependence. These have evaluated both
      short-term and long-term outcomes and have used German, Belgian, and Spanish
      costings. A fifth prospective cohort study collected real outcomes and data on
      expenditure during a 1 year study follow-up period. RESULTS: All five studies
      have produced consistent results, showing the use of acamprosate, which enhances
      abstinence rates, to reduce the total costs of treatment and thus be dominant
      over other rehabilitation strategies not involving pharmacotherapy. In all of the
      studies, the principal cost-driver is hospitalization. Although there is a short
      term increase in treatment costs associated with drug acquisition, these are
      recovered from long-term savings attributable to reduced hospitalization and
      rehabilitation costs.

PMID- 15939707
TI  - Histone h3 modifications in rat hepatic stellate cells by ethanol.
AB  - AIMS: Hepatic stellate cells (HSCs) play critical roles in the development of
      hepatic fibrosis caused by various agents including alcohol. Ethanol causes post
      translational modification in histone. The goal of this study is to investigate
      whether ethanol affected acetylation and methylation of histone H3 in rat HSCs.
      METHODS: We isolated and separated HSCs using collagenase perfusion of liver
      followed by Nycodenz density gradient centrifugation. HSCs were divided and
      treated with different concentrations of ethanol for various times. Histone was
      isolated using acid extraction method. Acetylation and methylation of histone H3
      at Lys9 was analysed by both western blot and fluorescein isothiocyanate (FITC)
      immunochemical stain. Acetylation of histone H3 at Lys9 (Ac-H3-lys9), Lys14 (Ac
      H3-Lys14), Lys18 (Ac-H3-lys18), or Lys23 (Ac-H3-lys23) was checked by western
      blotting. RESULTS: At lysine 9, ethanol caused dose-dependent increase of Ac-H3
      up to 200 mM. Ac-H3-lys9 increased with a maximum of 86-fold at 72 h and 200 mM
      ethanol treatment, and decreased thereafter. This increase was confirmed by both
      western blotting and FITC stain. At high dose, ethanol increased acetylation of
      histone H3 at Lys23 (Ac-H3-lys23), but it had no effect on Ac-H3-lys14 or Ac-H3
      lys18. The intensity of the FITC-labelled dimethyl-histone H3 at Lys9 (Me-H3
      lys9) antibody appeared to decrease slightly with increasing dose of ethanol. But
      this did not appear to change when monitored by western blotting. CONCLUSIONS:
      Ethanol caused dose and time-dependent increase in acetylation of histone H3 at
      Lys9, but not at Lys14 or Lys18. Compared with hepatocytes the Ac-H3-lys9 in HSCs
      required longer ethanol exposure. Levels of Me-H3-lys9 seemed to remain
      unaltered. Thus increase in Ac-H3-lys9 represents a nuclear-chromatin
      modification event in HSCs exposed to ethanol.

PMID- 15939708
TI  - Spreading out or concentrating weekly consumption: alcohol problems and other
      consequences within a UK population sample.
AB  - AIMS: To consider the consequences, within a UK population sample, of consuming a
      given amount of alcohol weekly in one or two sessions as against spreading it out
      over several sessions. METHODS: A new analysis of data from the UK components of
      the GENACIS survey of adults aged > or =18, was carried out. RESULTS: At low
      levels of weekly alcohol consumption those subjects whose usual drinking
      frequency was several times per week ('spreaders'), if anything, reported more
      alcohol problems than those who consumed alcohol only once or twice per week
      ('bingers'). As weekly consumption increased above approximately 11 units per
      week 'bingers' began to experience more problems than 'spreaders'. At the highest
      levels of consumption 'bingers' reported more positive experiences from drinking
      than did 'spreaders'. Subjects >54 years showed lower levels of weekly alcohol
      consumption than other subjects, and relationships between problems, drinking
      level, and drinking pattern were less in evidence. Females drank less alcohol and
      experienced fewer alcohol-related problems than did their male counterparts.
      However, at high-consumption levels, female 'bingers' experienced fewer problems
      than male 'bingers'. CONCLUSIONS: For most but not all the variables studied,
      both drinking level and drinking pattern are important determinants of problems
      experienced. Binge drinking for people who drink more than approximately 11 units
      per week is an obvious target for harm minimization.

PMID- 15939709
TI  - Do lipids contribute to the lack of cardio-protective effect of binge drinking:
      alcohol consumption and lipids in three eastern European countries.
AB  - AIMS: The cardio-protective effect of moderate alcohol consumption is partly
      mediated by HDL cholesterol. However, epidemiological studies suggest that binge
      drinking may not be associated with reduced risk of heart disease; a possible
      explanation is that the relationship of blood lipids with binge drinking is
      different from that with moderate intake. We investigated this hypothesis in a
      population study in three eastern European countries. METHODS: We conducted a
      cross-sectional study in random population samples in Novosibirsk (Russia),
      Krakow (Poland) and Karvina (Czech Republic). A sub-sample of 282 men aged 45-64
      years who provided a fasting blood sample were analysed. Annual alcohol intake
      and the frequency of heavy binge drinking (> or =140 g of ethanol per session)
      were estimated from a graduated frequency questionnaire. RESULTS: Annual intake
      of alcohol was positively associated with total and HDL cholesterol. After
      controlling for annual intake, the frequency of heavy binge drinking was
      associated with increased concentrations of total and HDL cholesterol. By
      combining annual intake and drinking pattern, we found that men consuming >8 l of
      alcohol per year who had a heavy binge at least once a month had the mean total,
      HDL and LDL cholesterol 1.69 (SE 0.35), 0.61 (0.11) and 0.97 (0.34) mmol/l,
      respectively, higher than non-drinkers; this resulted in more favourable ratios
      of total and LDL cholesterol relative to HDL cholesterol in frequent heavy
      bingers. Triglycerides were not related to alcohol intake or binge drinking.
      CONCLUSIONS: Blood lipids do not seem to explain the apparent lack of the cardio
      protective effect of binge drinking reported in epidemiological studies.

PMID- 15939710
TI  - Short-term recovery from alcohol abuse or dependence: any evidence of a
      relationship with treatment use in a general population sample?
AB  - AIMS: To test whether survey respondents who report alcohol misuse in the past
      year are more likely to be abstinent or binge-free in the past 30 days if they
      have used treatment, than if they have not. METHODS: Analysis of data from the
      2002 US National Survey on Drug Use and Health was obtained. RESULTS: A total of
      5730 respondents scored positive for alcohol abuse or dependence in the preceding
      year. Fewer than 10% had used any treatment for alcohol or drugs in this period,
      but this was associated with a 10% increase in the past-month abstinence and past
      month binge-free drinking compared with respondents who did not access treatment.
      Such an apparent short-term recovery appeared greater in those whose treatment
      had been received in a formal treatment setting, a doctor's office, or in self
      help groups than in the emergency room or in prison. CONCLUSIONS: Even if part of
      the association between treatment and recent abstinence and non-binge drinking
      was causal, indicating that treatment has some impact, it is a pathway chosen
      only by the minority.

PMID- 15939712
TI  - High-dose sequential chemotherapy followed by autologous stem cell
      transplantation in relapsed and refractory aggressive non-Hodgkin's lymphoma:
      results of a multicenter phase II study.
AB  - BACKGROUND: Combination chemotherapy can cure patients with non-Hodgkin's
      lymphoma (NHL), but those who suffer treatment failure or relapse still have a
      poor prognosis. High-dose chemotherapy (HDCT) with autologous stem cell
      transplantation (ASCT) can improve the outcome of these patients. We evaluated an
      intensified high-dose sequential chemotherapy program with a final myeloablative
      course. PATIENTS AND METHODS: Inclusion criteria were age 18-65 years,
      histologically proven primary progressive or relapsed aggressive NHL and
      eligibility for HDCT. The therapy consists of two cycles DHAP: dexamethasone 40
      mg (day 1-4), high-dose cytarabine 2 g/m2 12q (day 2), cisplatin 100 mg/m2 (day
      51); patients with partial (PR) or complete remission (CR) received
      cyclophosphamide 4 g/m2 (day 37), followed by peripheral blood stem cell (PBSC)
      harvest; methotrexate 8 g/m2 (day 1) plus vincristine 1.4 mg/m2 (day 51); and
      etoposide 500 mg/m2 (day 58-62). The final myeloblative course was BEAM:
      cytarabine 200 mg/m2 12q (day 81-84), etoposide 150 mg/m2 12q (day 81-84),
      melphalan 140 mg/m2 (day 80), carmustin 300 mg/m2 (day 80) followed by PBSCT.
      RESULTS: Fifty-seven patients (median age 43 years, range 24-65) were enrolled:
      23 (40%) patients were refractory to primary therapy and 34 (60%) patients had
      relapsed NHL. The response rate (RR) after 2 cycles of DHAP was 72% (9% CR, 63%
      PR) and at the final evaluation (100 days post transplantation) 43% (32% CR, 11%
      PR). Toxicity was tolerable. Median follow-up was 25 months (range 1-76 months).
      Freedom from second failure (FF2F) and overall survival (OS) at 2 years were 25%
      and 47% for all patients, respectively. FF2F at 2 years for patients with relapse
      and for patients refractory to primary therapy were 35% and 9% (P=0.0006),
      respectively. OS at 2 years for patients with relapse and for patients refractory
      to primary therapy were 58% and 24% (P=0.0044), respectively. CONCLUSIONS: We
      conclude that this regimen is feasible, tolerable and effective in patients with
      relapsed NHL. In contrast, the results in patients with progressive disease are
      unsatisfactory. This program is currently being modified by addition of rituximab
      for patients with relapsed aggressive NHL.

PMID- 15939713
TI  - Prognostic value of interim FDG-PET after two or three cycles of chemotherapy in
      Hodgkin lymphoma.
AB  - BACKGROUND: Long-term survival from Hodgkin lymphoma (HL) is 80-90%, but the
      treatment has serious late adverse effects. Modern risk-adapted treatment
      requires accurate assessment of the patient's prognosis. This investigation
      assessed the value of positron emission tomography (PET) with 2-[18F]fluoro-2
      deoxy-D-glucose (FDG-PET) after two or three cycles of chemotherapy for
      prediction of progression-free survival (PFS) and overall survival (OS). PATIENTS
      AND METHODS: A total of 85 patients with HL underwent FDG-PET after two or three
      cycles of chemotherapy. Median follow-up was 3.3 years. FDG-PET results were
      related to PFS and OS using Kaplan-Meier analysis. Regression analyses were
      employed to test for independence of established pretreatment prognostic factors.
      RESULTS: After two or three cycles of chemotherapy, 63 patients had negative FDG
      PET scans, nine patients had minimal residual uptake (MRU) and 13 patients had
      positive scans. Three PET-negative patients and one patient from the MRU group
      relapsed. In the PET-positive group, nine patients progressed and two died.
      Survival analyses showed highly significant associations between early interim
      FDG-PET and PFS (P <0.0001) and OS (P <0.03). All advanced-stage patients with
      positive interim FDG-PET relapsed within 2 years. CONCLUSION: Early interim FDG
      PET is an accurate and independent predictor of PFS and OS in HL. A positive
      interim FDG-PET is highly predictive of relapse in advanced-stage disease.

PMID- 15939714
TI  - A phase I/II and pharmacokinetic study of irinotecan in combination with
      capecitabine as first-line therapy for advanced colorectal cancer.
AB  - PURPOSE: The aim of this study was to determine in patients with previously
      untreated advanced colorectal cancer the maximum tolerated dose (MTD) and safety
      profile of irinotecan in combination with capecitabine, to identify a recommended
      dose and to determine the response rate and time to disease progression. In
      addition, we aimed to explore the pharmacokinetic parameters of irinotecan and
      capecitabine when used in different sequences of administration, with irinotecan
      infusion either prior to or after the first intake of capecitabine. PATIENTS AND
      METHODS: One hundred patients were included: 43 patients were recruited into an
      extended phase I trial of alternating escalation in dose of both drugs where
      irinotecan was administered intravenously (i.v) on day 1 after first intake of
      capecitabine taken from days 1-14 twice daily, with cycles repeated every 3
      weeks. After the determination of recommended dose a further 57 patients were
      treated in a phase II evaluation with the reverse sequence of drugs on day 1.
      Pharmacokinetic analysis was performed in patients treated at the recommended
      dose in two cohorts of patients in which the sequence of the first administration
      of each drug was reversed. RESULTS: The MTD of the combination was determined as
      irinotecan 300 mg/m2, with capecitabine 2000 mg/m2/day. Dose limiting toxicities
      were neutropenia and diarrhoea. The recommended dose is irinotecan intravenous
      (i.v.) 250 mg/m2 day 1 and capecitabine 2000 mg/m2/day days 1-14, every 3 weeks.
      Treatment was well tolerated, with diarrhoea the most common serious toxicity.
      Response rate in the phase II cohort was 42% [95% confidence interval (CI) 29% to
      56%]. Median duration of response was 7.7 months (95% CI 7.5-8.9). Median time to
      progression was 8.3 months (95% CI 5.8-10). No significant effect on irinotecan
      pharmacokinetics was observed whatever the intake of capecitabine before or after
      irinotecan infusion. An effect of irinotecan on capecitabine and some
      capecitabine metabolites was observed, but irinotecan did not effect 5
      fluorouracil (5-FU) pharmacokinetics. CONCLUSIONS: Irinotecan in combination with
      capecitabine is a well tolerated regimen with an activity comparable to, but more
      convenient than, irinotecan-5-FU i.v. combinations in patients with previously
      untreated advanced colorectal cancer. The pharmacokinetic data suggest that the
      sequence of administration does not impact significantly on the metabolism of the
      two drugs.

PMID- 15939715
TI  - Bevacizumab--current status and future directions.
AB  - Angiogenesis is crucial to tumour initiation, survival and metastasis. Vascular
      endothelial growth factor (VEGF) is one of the most important pro-angiogenic
      factors in cancer development. Bevacizumab (a humanised monoclonal antibody
      against VEGF) has a reasonable safety profile and proven efficacy in a phase III
      trial in advanced colorectal cancer. Efficacy of Bevacizumab also looks promising
      in non small cell lung cancer, renal cancer and a variety of other solid tumours.
      Questions still surround optimal dosing and the appropriate selection of patients
      who are most likely to benefit. Future trials will address these questions and
      provide further translational insights.

PMID- 15939716
TI  - Communicating prognosis in cancer care: a systematic review of the literature.
AB  - Prognosis is an issue that most doctors and patients describe as difficult to
      discuss and the best way of presenting prognostic information to optimise patient
      understanding, psychological adjustment and decision-making is uncertain. A
      systematic review of the literature was conducted with the aim of clarifying the
      current available knowledge of patient preferences, clinician views and current
      practice regarding the communication of prognosis. Eleven primary research
      questions guided organisation of the review findings, which were: patient
      preferences for prognostic information and preferred style of communicating
      prognosis; disclosure of prognosis to family members; physicians' views on
      communication of prognosis; current practice of delivering prognostic
      information; patient understanding and awareness of prognostic information;
      cultural differences in preferences and understanding; impact of prognostic
      information on patient outcomes; and interventions to facilitate prognostic
      discussion. Predictors of patient preferences for and understanding of prognostic
      information were also summarised. Studies are summarised under the subcategories
      according to the participants' disease stage. It was found that the majority of
      the published research has been conducted in the early stage cancer setting
      providing mostly descriptive evidence, and there is little evidence of the best
      method of communicating prognosis or of the impact of prognostic information on
      patient outcomes.

PMID- 15939717
TI  - Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery
      alone for gastric cancer: 7-year results of the FFCD randomized phase III trial
      (8801).
AB  - BACKGROUND: The aim of this study was to evaluate the efficacy of adjuvant
      chemotherapy after resection for gastric cancer in a randomized controlled trial.
      PATIENTS AND METHODS: After curative resection, stage II-III-IVM0 gastric cancer
      patients were randomly assigned to postoperative chemotherapy or surgery alone. 5
      Fluorouracil (5-FU) 800 mg/m(2) daily (5-day continuous infusion) was initiated
      before day 14 after resection. One month later, four 5-day cycles of 5-FU (1
      g/m(2) per day) plus cisplatin (100 mg/m(2) on day 2) were administered every 4
      weeks. RESULTS: The study was closed prematurely after enrollment of 260 patients
      (79.7% N+), owing to poor accrual. At 97.8 months median follow-up, 5- and 7-year
      overall survival were 41.9% and 34.9% in the control group versus 46.6% and 44.6%
      in the chemotherapy group (P=0.22). Cox model hazard ratios were 0.74 [95%
      confidence interval (CI) 0.54-1.02; P=0.063] for death and 0.70 (95% CI 0.51
      0.97; P=0.032) for recurrence. An invaded/removed lymph nodes ratio >0.3 was the
      main independent poor prognostic factor identified by multivariate analysis
      (P=0.0001). Because of toxicity, only 48.8% of patients received more than 80% of
      the planned dose. CONCLUSION: There was no statistically significant survival
      benefit with this toxic cisplatin-based adjuvant chemotherapy, but a risk
      reduction in recurrence was observed.

PMID- 15939718
TI  - Prognostic indexes in follicular lymphoma: a comparison of different prognostic
      systems.
AB  - BACKGROUND: The International Prognostic Index (IPI), initially designed for
      aggressive lymphomas, is also used in follicular lymphoma (FL) and other indolent
      lymphomas. Two new prognostic indexes have recently been proposed for FL [the
      Italian Lymphoma Intergroup (ILI) Index and the Follicular Lymphoma International
      Prognostic Index (FLIPI)]. PATIENTS AND METHODS: Three indexes, IPI [age >60
      years, extranodal involvement two or more sites, elevated lactate dehydrogenase
      (LDH), Eastern Cooperative Oncology Group performance status > or =2, stage > or
      =3], ILI (age >60 years, extranodal involvement two or more sites, elevated LDH,
      male sex, B symptoms, erythrocyte sedimentation rate > or =30 mm first hour) and
      FLIPI (age >60 years, stage > or =3, elevated LDH, nodal involvement five or
      more, haemoglobin level < or =12 g/dl) were calculated in 411 patients with FL.
      RESULTS: Overall concordance between the three indexes was 54%. A total of 126
      (31%) patients were included in the high-risk group according to IPI, 131 (32%)
      according to ILI and 157 (38%) after FLIPI application. Ten-year overall survival
      rates after applying the prognostic indexes (IPI, ILI and FLIPI) were,
      respectively: 72%, 71% and 72%, in the low-risk group; 51%, 60% and 49% in the
      intermediate-risk group; and 24%, 16% and 31% in the high-risk group.
      CONCLUSIONS: In this series, all three indexes, IPI, ILI and FLIPI, were useful
      to classify FL patients into differentiated risk groups, although the FLIPI
      identified a larger proportion of high-risk patients than the IPI and ILI.

PMID- 15939719
TI  - Is the new WHO classification of neuroendocrine tumours useful for selecting an
      appropriate treatment?
AB  - BACKGROUND: Neuroendocrine tumours (NETs) are a rare and heterogeneous group of
      neoplasms. The most recent WHO classification provides clinical tools and
      indications to make the diagnosis and to suggest the correct treatment in
      different subgroups of patients. The aim of this trial was to apply the new
      classification criteria in clinical practice and, accordingly, to choose the most
      appropriate treatment. PATIENTS AND METHODS: Thirty-one evaluable patients, not
      previously treated, classified as advanced well differentiated NETs according to
      the new classification, were given long-acting release octreotide 30 mg every 28
      days until evidence of disease progression. The treatment activity was evaluated
      according to objective, biochemical and symptomatic responses. Safety and
      tolerability were also assessed. RESULTS: Two partial objective tumour responses
      were obtained (6%), stabilization occurred in 16 patients (52%) and 95% of
      patients had a disease stabilisation lasting > or =6 months. However, eight
      patients showed rapid disease progression within 6 months of therapy and six
      patients after 6 months. Biochemical responses, evaluated by changes in serum
      chromogranine A levels were reported in 20/24 patients (83%). Symptomatic
      responses were observed in 6/14 patients (43%): a complete syndrome remission in
      one patient, partial syndrome remission in five patients, no change in four
      patients and progressive disease in four patients. The median overall survival
      was not reached, and the median time to disease progression was 18 months (range
      1-49 months). The treatment was well tolerated, no severe adverse events were
      observed and no patient withdrew from the study because of adverse events.
      CONCLUSIONS: The WHO classification enables identification of low-grade NET
      patients who may be suitable for hormonal treatment. Octreotide LAR was seen to
      be effective in controlling the disease and was well tolerated. However, eight
      patients failed to respond to the treatment, despite histological evidence of a
      well differentiated tumour according to the new classification. This suggests
      that further histological examination should be carried out, especially in
      patients with visceral metastases and a short disease-free interval.

PMID- 15939720
TI  - Clinical significance of cytogenetics and interphase fluorescence in situ
      hybridization analysis in newly diagnosed multiple myeloma in Taiwan.
AB  - BACKGROUND: The incidence of multiple myeloma (MM) is lower in Asia than in
      Western countries. However, it is not known whether cytogenetic abnormalities
      (CA) characteristic of MM in Asia differ from those documented in the West.
      PATIENTS AND METHODS: We analyzed CA by conventional cytogenetics (CG) and/or
      fluorescence in situ hybridization (FISH), assessed their clinical significance
      in 150 Chinese MM patients and compared our data with that derived from Western
      countries. RESULTS: CA were detected by CG (CG_CA) in 44 (29.3%) of the 150
      patients and by FISH (FISH_CA) in 59 (67%) of the 88 patients studied. Presence
      of either CG_CA or FISH_CA was associated with a poor prognosis. Patients with
      CG_CA and hyperdiploid chromosomes, always associated with several trisomies, had
      a longer survival (median 25 months versus 12 months; P=0.025) in comparison with
      those with non-hyperdiploid chromosomes, usually associated with a monosomy
      13/partial deletion of 13q (Delta13) and a rearrangement of 14q32. A novel
      recurrent CG_CA, add(19)(p13), was found in four patients: all males with
      immunoglobulin G/lambda isotypes, extramedullary myeloma at diagnosis and a poor
      prognosis. Three groups of patients with significantly different survival,
      CG_Delta13, FISH_Delta13 but without CG_Delta13, and neither CG_Delta13 nor
      FISH_Delta13 (median 9 versus 15 versus 32 months; P=0.013) were identified.
      CONCLUSIONS: We conclude that MM CA in our patients are similar to those noted in
      Western countries, and that combined CG and FISH analysis can predict prognosis.
      The clinical significance of add(19)(p13) needs to be further investigated.

PMID- 15939721
TI  - Staged surgical management of hypoplastic left heart syndrome: a single
      institution 12 year experience.
AB  - OBJECTIVE: To describe a 12 year experience with staged surgical management of
      the hypoplastic left heart syndrome (HLHS) and to identify the factors that
      influenced outcome. METHODS: Between December 1992 and June 2004, 333 patients
      with HLHS underwent a Norwood procedure (median age 4 days, range 0-217 days).
      Subsequently 203 patients underwent a bidirectional Glenn procedure (stage II)
      and 81 patients underwent a modified Fontan procedure (stage III). Follow up was
      complete (median interval 3.7 years, range 32 days to 11.3 years). RESULTS: Early
      mortality after the Norwood procedure was 29% (n = 95); this decreased from 46%
      (first year) to 16% (last year; p < 0.05). Between stages, 49 patients died, 27
      before stage II and 22 between stages II and III. There were one early and three
      late deaths after stage III. Actuarial survival (SEM) was 58% (3%) at one year
      and 50% (3%) at five and 10 years. On multivariable analysis, five factors
      influenced early mortality after the Norwood procedure (p < 0.05). Pulmonary
      blood flow supplied by a right ventricle to pulmonary artery (RV-PA) conduit,
      arch reconstruction with pulmonary homograft patch, and increased operative
      weight improved early mortality. Increased periods of cardiopulmonary bypass and
      deep hypothermic circulatory arrest increased early mortality. Similar factors
      also influenced actuarial survival after the Norwood procedure. CONCLUSION: This
      study identified an improvement in outcome after staged surgical management of
      HLHS, which was primarily attributable to changes in surgical technique. The RV
      PA conduit, in particular, was associated with a notable and independent
      improvement in early and actuarial survival.

PMID- 15939722
TI  - Usefulness of myocardial parametric imaging to evaluate myocardial viability in
      experimental and in clinical studies.
AB  - OBJECTIVE: To evaluate whether myocardial parametric imaging (MPI) is superior to
      visual assessment for the evaluation of myocardial viability. METHODS AND
      RESULTS: Myocardial contrast echocardiography (MCE) was assessed in 11 pigs
      before, during, and after left anterior descending coronary artery occlusion and
      in 32 patients with ischaemic heart disease by using intravenous SonoVue
      administration. In experimental studies perfusion defect area assessment by MPI
      was compared with visually guided perfusion defect planimetry. Histological
      assessment of necrotic tissue was the standard reference. In clinical studies
      viability was assessed on a segmental level by (1) visual analysis of myocardial
      opacification; (2) quantitative estimation of myocardial blood flow in regions of
      interest; and (3) MPI. Functional recovery between three and six months after
      revascularisation was the standard reference. In experimental studies, compared
      with visually guided perfusion defect planimetry, planimetric assessment of
      infarct size by MPI correlated more significantly with histology (r2 = 0.92
      versus r2 = 0.56) and had a lower intraobserver variability (4% v 15%, p < 0.05).
      In clinical studies, MPI had higher specificity (66% v 43%, p < 0.05) than visual
      MCE and good accuracy (81%) for viability detection. It was less time consuming
      (3.4 (1.6) v 9.2 (2.4) minutes per image, p < 0.05) than quantitative blood flow
      estimation by regions of interest and increased the agreement between observers
      interpreting myocardial perfusion (kappa = 0.87 v kappa = 0.75, p < 0.05).
      CONCLUSION: MPI is useful for the evaluation of myocardial viability both in
      animals and in patients. It is less time consuming than quantification analysis
      by regions of interest and less observer dependent than visual analysis. Thus,
      strategies incorporating this technique may be valuable for the evaluation of
      myocardial viability in clinical routine.

PMID- 15939723
TI  - Are drug eluting stents really worth the money?

PMID- 15939724
TI  - Carboxyhaemoglobin concentration, smoking habit, and mortality in 25 years in the
      Renfrew/Paisley prospective cohort study.
AB  - OBJECTIVE: To investigate how carboxyhaemoglobin concentration is related to
      smoking habit and to assess whether carboxyhaemoglobin concentration is related
      to mortality. DESIGN: Prospective cohort study. SETTING: Residents of the towns
      of Renfrew and Paisley in Scotland. PARTICIPANTS: The whole Renfrew/Paisley
      study, conducted between 1972 and 1976, consisted of 7048 men and 8354 women aged
      45-64 years. This study was based on 3372 men and 4192 women who were screened
      after the measurement of carboxyhaemoglobin concentration was introduced about
      halfway through the study. MAIN OUTCOME MEASURES: Deaths from coronary heart
      disease (CHD), stroke, chronic obstructive pulmonary disease (COPD), lung cancer,
      and all causes in 25 years after screening. RESULTS: Carboxyhaemoglobin
      concentration was related to self reported smoking and for each smoking category
      was higher in participants who reported inhaling than in those who reported not
      inhaling. Carboxyhaemoglobin concentration was positively related to all causes
      of mortality analysed (relative rates associated with a 1 SD (2.93) increase in
      carboxyhaemoglobin for all causes, CHD, stroke, COPD, and lung cancer were 1.26
      (95% confidence interval (CI) 1.19 to 1.34), 1.19 (95% CI 1.13 to 1.26), 1.19
      (95% CI 1.13 to 1.26), 1.64 (95% CI 1.47 to 1.84), and 1.69 (95% CI 1.60 to
      1.79), respectively). Adjustment for self reported cigarette smoking attenuated
      the associations but they remained relatively strong. CONCLUSIONS: Self reported
      smoking data were validated by the objective measure of carboxyhaemoglobin
      concentration. Since carboxyhaemoglobin concentration remained associated with
      mortality after adjustment for smoking, carboxyhaemoglobin seems to capture more
      of the risk associated with smoking tobacco than does self reported tobacco
      consumption alone. Analysing mortality by self reported cigarette smoking
      underestimates the strength of association between smoking and mortality.

PMID- 15939725
TI  - Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior
      myocardium.
AB  - OBJECTIVE: To determine whether the Bezold-Jarisch reflex or enhancement of vagal
      nerves, which are preferentially distributed in the inferoposterior myocardium,
      results from exercise induced ischaemia in this region. METHODS: On the basis of
      exercise myocardial scintigraphy and coronary angiography, 145 patients were
      classified as follows: group I, 34 patients with inferoposterior ischaemia; group
      A, 32 with anterior ischaemia; and control, 79 without ischaemia. The relation
      between ischaemic areas and ECG leads with ST segment changes and vagal
      modulation assessed by heart rate variability (HRV) (high frequency (HF)
      component (0.15-0.40 Hz) and coefficient of HF component variance (CCVHF), which
      is the square root of HF divided by mean RR interval) were assessed. RESULTS: The
      rate of ST segment depression in any lead did not differ between group I and
      group A. HF and CCV(HF) were similar before exercise but higher in group I than
      in group A and the control group after exercise (mean (SEM) HF: 94 (17) ms2, 41
      (7) ms2, and 45 (6) ms2, respectively, p = 0.021; CCV(HF): 1.18 (0.09)%, 0.81
      (0.07)%, and 0.89 (0.05)%, p = 0.0053). Furthermore, the percentage change in
      CCV(HF) before and after exercise was higher in group I than in group A or
      controls (mean (SEM) 22 (10)%, -24 (4)%, and -21 (3)%, p < 0.0001). The optimal
      cut off for diagnosis of inferoposterior ischaemia was -5% with a sensitivity of
      74%, specificity 75%, and accuracy 75%. CONCLUSIONS: Vagal modulation as assessed
      by HRV analysis was enhanced in association with exercise induced inferoposterior
      ischaemia. Exercise ECG testing combined with HRV analysis would increase
      accuracy in the diagnosis of ischaemic areas in selected patients with angina
      pectoris.

PMID- 15939726
TI  - Non-invasive evaluation of the myocardial substrate of cardiac amyloidosis by
      gadolinium cardiac magnetic resonance.
AB  - OBJECTIVE: To investigate the prevalence and distribution of gadolinium (Gd)
      enhancement at cardiac magnetic resonance (CMR) imaging in patients with cardiac
      amyloidosis (CA) and to look for associations with clinical, morphological, and
      functional features. PATIENTS AND DESIGN: 21 patients with definitely diagnosed
      CA (nine with immunoglobulin light chain amyloidosis and 12 transthyretin
      related) underwent Gd-CMR. RESULTS: Gd enhancement was detected in 16 of 21 (76%)
      patients. Sixty six of 357 (18%) segments were enhanced, more often at the mid
      ventricular level. Transmural extension of enhancement within each patient
      significantly correlated with left ventricular (LV) end systolic volume (r =
      0.58). The number of enhanced segments correlated with LV end diastolic volume (r
      = 0.76), end systolic volume (r = 0.6), and left atrial size (r = 0.56). Segments
      with > 50% extensive transmural enhancement more often were severely hypokinetic
      or akinetic (p = 0.001). Patients with > 2 enhanced segments had significantly
      lower 12 lead QRS voltage and Sokolow-Lyon index. No relation was apparent with
      any other clinical, morphological, functional, or histological characteristics.
      CONCLUSION: Gd enhancement is common but not universally present in CA, probably
      due to expansion of infiltrated interstitium. The segmental and transmural
      distribution of the enhancement is highly variable, and mid-ventricular regions
      are more often involved. Enhancement appears to be associated with impaired
      segmental and global contractility and a larger atrium.

PMID- 15939727
TI  - Demographic and temporal trends in out of hospital sudden cardiac death in
      Belfast.
AB  - OBJECTIVE: To determine the epidemiology of out of hospital sudden cardiac death
      (OHSCD) in Belfast from 1 August 2003 to 31 July 2004. DESIGN: Prospective
      examination of out of hospital cardiac arrests by using the Utstein style and
      necropsy reports. World Health Organization criteria were applied to determine
      the number of sudden cardiac deaths. RESULTS: Of 300 OHSCDs, 197 (66%) in men,
      mean age (SD) 68 (14) years, 234 (78%) occurred at home. The emergency medical
      services (EMS) attended 279 (93%). Rhythm on EMS arrival was ventricular
      fibrillation (VF) in 75 (27%). The call to response interval (CRI) was mean (SD)
      8 (3) minutes. Among patients attended by the EMS, 9.7% were resuscitated and
      7.2% survived to leave hospital alive. The CRI for survivors was mean (SD) 5 (2)
      minutes and for non-survivors, 8 (3) minutes (p < 0.001). Ninety one (30%) OHSCDs
      were witnessed; of these 91 patients 48 (53%) had VF on EMS arrival. The survival
      rate for witnessed VF arrests was 20 of 48 (41.7%): all 20 survivors had VF as
      the presenting rhythm and CRI < or = 7 minutes. The European age standardised
      incidence for OHSCD was 122/100,000 (95% confidence interval 111 to 133) for men
      and 41/100,000 (95% confidence interval 36 to 46) for women. CONCLUSION: Despite
      a 37% reduction in heart attack mortality in Ireland over the past 20 years, the
      incidence of OHSCD in Belfast has not fallen. In this study, 78% of OHSCDs
      occurred at home.

PMID- 15939728
TI  - Identification of patients with evolving coronary syndromes by using statistical
      models with data from the time of presentation.
AB  - OBJECTIVE: To derive statistical models for the diagnosis of acute coronary
      syndromes by using clinical and ECG information at presentation and to assess
      performance, portability, and calibration of these models, as well as how they
      may be used with cardiac marker proteins. DESIGN AND METHODS: Data from 3462
      patients in four UK teaching hospitals were used. Inputs for 8, 14, 25, and 43
      factor logistic regression models were selected by using log10 likelihood ratios
      (log10 LRs). Performance was analysed by receiver operating characteristic
      curves. RESULTS: A 25 factor model derived from 1253 patients from one centre was
      selected for further study. On training data, 98.2% of ST elevation myocardial
      infarctions (STEMIs) and 96.2% of non-ST elevation myocardial infarctions (non
      STEMIs) were correctly classified, whereas only 2.1% of non-cardiac cases were
      incorrectly classified. On data from three other centres, 97.3% of STEMIs and
      91.9% of non-STEMIs were correctly classified. Differences in log10 LRs for
      individual inputs from different centres accounted for the decline in performance
      when models were applied to unseen data. Classification was improved when output
      was combined with either clinical opinion or marker proteins. CONCLUSIONS:
      Logistic regression models based on data available at presentation can classify
      patients with chest pain with a high degree of accuracy, particularly when
      combined with clinical opinion or marker proteins.

PMID- 15939729
TI  - Supervision and responsibility: The Royal College of Anaesthetists National
      Audit.
AB  - BACKGROUND: The Royal College of Anaesthetists audited consultant supervision and
      responsibility in anaesthesia in the UK during 2003. METHODS: Consultants
      (supervising) and non-consultants (supervised) were surveyed on their attitudes
      to supervision, experience of their own hospital system for supervision and of
      induction for new starters. Local coordination was achieved through anaesthesia
      audit coordinators who provided information on local policies, induction
      programmes and anaesthesia charts. Supervision was audited over a 5-day period.
      RESULTS: 135 departments of anaesthesia took part (43% of 315 departments),
      questionnaires being returned by 2297 anaesthetists. Anaesthesia record charts in
      use do not meet criteria considered desirable locally. Most trainees, but less
      than half staff grade/associate specialists, received an induction programme,
      often not supported by written documentation. Consultants find conflicting
      demands of service and supervision difficult. Many work in systems which do not
      permit providing direct, immediate support to those supervised. Most
      anaesthetists think supervision is very important. Around half disagree with
      national guidance that every NHS patient should have a named consultant. Two per
      cent of non-consultants during the audit period reported assistance from
      consultants not being obtainable soon enough. CONCLUSIONS: This audit found
      departure from standards and the potential for risk and failure. New standards
      may be needed regarding anaesthesia record sheets, induction, accountability,
      when to seek help and care of sick patients. Supervision systems in over 40% of
      hospitals need review to ensure they provide a named consultant and immediate
      direct support for elective lists.

PMID- 15939730
TI  - Anaesthetic preconditioning but not postconditioning prevents early activation of
      the deleterious cardiac remodelling programme: evidence of opposing genomic
      responses in cardioprotection by pre- and postconditioning.
AB  - BACKGROUND: Anaesthetic preconditioning (A_PreC) and postconditioning (A_PostC)
      both provide protection against ischaemia-reperfusion in the heart. However, post
      ischaemic gene responses may differ between the two therapeutic strategies.
      METHODS: Isolated perfused rat hearts were exposed to 40 min test ischaemia
      followed by 3 h reperfusion and used to determine transcriptional changes in
      response to A_PreC and A_PostC. A_PreC was induced by 15 min of isoflurane 2.1
      vol% followed by 10 min of washout, and A_PostC was induced by 15 min of
      isoflurane 2.1 vol% administered at the onset of reperfusion. Untreated hearts
      served as ischaemic control (ISCH). Coupled-two way clustering (CTWC) and
      principal component analysis (PCA) were used to identify gene expression
      patterns. RESULTS: A_PreC (7[sd 1]%) and A_PostC (6[2]%) produced a similar
      decrease in infarct size (ISCH 36[1]%, P<0.05). However, post-ischaemic genomic
      reprogramming was completely different. Few genes were jointly regulated (2.1 per
      thousand of upregulated genes and 1.3% of downregulated genes). Eight stable gene
      clusters including three subclusters emerged from CTWC and were related to
      inflammation, signalling, ion channels, transcription factors, long interspersed
      repetitive DNA, heat shock response and remodelling. Two stable sample clusters
      were identified for postconditioned hearts (first cluster) and for all other
      protocols (second cluster), emphasizing the unique cardiac phenotype elicited by
      A_PostC. PCA revealed a close genomic relationship between A_PreC and non
      ischaemic healthy myocardium. CONCLUSIONS: A_PreC, but not A_PostC, induces a
      post-ischaemic gene expression profile similar to virgin myocardium and prevents
      activation of the deleterious cardiac remodelling programme. Hence A_PreC and
      A_PostC are not interchangeable with respect to their molecular outcome in the
      heart.

PMID- 15939731
TI  - Mechanisms of improvement of respiratory failure in patients with restrictive
      thoracic disease treated with non-invasive ventilation.
AB  - BACKGROUND: Nocturnal non-invasive ventilation (NIV) is an effective treatment
      for hypercapnic respiratory failure in patients with restrictive thoracic
      disease. We hypothesised that NIV may reverse respiratory failure by increasing
      the ventilatory response to carbon dioxide, reducing inspiratory muscle fatigue,
      or enhancing pulmonary mechanics. METHODS: Twenty patients with restrictive
      disease were studied at baseline (D0) and at 5-8 days (D5) and 3 months (3M).
      RESULTS: Mean (SD) daytime arterial carbon dioxide tension (Paco(2)) was reduced
      from 7.1 (0.9) kPa to 6.6 (0.8) kPa at D5 and 6.3 (0.9) kPa at 3M (p = 0.004),
      with the mean (SD) hypercapnic ventilatory response increasing from 2.8 (2.3)
      l/min/kPa to 3.6 (2.4) l/min/kPa at D5 and 4.3 (3.3) l/min/kPa at 3M (p = 0.044).
      No increase was observed in measures of inspiratory muscle strength including
      twitch transdiaphragmatic pressure, nor in lung function or respiratory system
      compliance. CONCLUSIONS: These findings suggest that increased ventilatory
      response to carbon dioxide is the principal mechanism underlying the long term
      improvement in gas exchange following NIV in patients with restrictive thoracic
      disease. Increases in respiratory muscle strength (sniff oesophageal pressure and
      sniff nasal pressure) correlated with reductions in the Epworth sleepiness score,
      possibly indicating an increase in the ability of patients to activate
      inspiratory muscles rather than an improvement in contractility.

PMID- 15939732
TI  - Intravenous aminophylline in patients admitted to hospital with non-acidotic
      exacerbations of chronic obstructive pulmonary disease: a prospective randomised
      controlled trial.
AB  - BACKGROUND: Intravenous aminophylline is commonly used in the treatment of
      exacerbations of chronic obstructive pulmonary disease (COPD), despite limited
      evidence for its efficacy and known risks of toxicity. We hypothesised that
      adding intravenous aminophylline to conventional treatment would not produce
      clinically important changes in the speed of spirometric or symptomatic recovery
      or shorten hospital stay in patients with exacerbations of COPD. METHODS: Eighty
      patients admitted to hospital with non-acidotic exacerbations of COPD were
      recruited at admission to a randomised, double blind, placebo controlled study
      comparing intravenous aminophylline 0.5 mg/kg/hour after an appropriate loading
      dose with an equivalent volume of 0.9% saline. The primary outcome was the change
      in post-bronchodilator forced expiratory volume in 1 second (FEV(1)) over the
      first 5 days of the admission. Secondary end points were changes in self-reported
      breathlessness, arterial blood gas tensions, forced vital capacity (FVC), and
      length of hospital stay. RESULTS: There was no difference in the post
      bronchodilator FEV(1) over the first 5 days between the aminophylline and placebo
      groups. In the aminophylline group, 2 hours of treatment produced a small but
      significant rise in arterial pH (p = 0.001) and a fall in arterial carbon dioxide
      tension (p = 0.01) compared with placebo treatment. There were no differences in
      the severity of breathlessness, post-bronchodilator FVC, or length of hospital
      stay between the groups. Nausea was a more frequent side effect in the
      aminophylline group (46% v 22%; p<0.05), but palpitations and headache were noted
      equally in both groups. CONCLUSIONS: Although intravenous aminophylline produced
      small improvements in acid-base balance, these did not influence the subsequent
      clinical course. No evidence was found for any clinically important additional
      effect of aminophylline treatment when used with high dose nebulised
      bronchodilators and oral corticosteroids. Given its known toxicity, we cannot
      therefore recommend the use of intravenous aminophylline in the treatment of non
      acidotic COPD exacerbations.

PMID- 15939733
TI  - European plant science: a field of opportunities.
AB  - Plants have a pivotal role in eco- and agricultural systems. Genomics is driving
      a rapid expansion of our understanding of how genes, individually and in
      networks, determine plant function. Technological developments in breeding and
      genomics are providing strategies to translate this knowledge into crop
      improvement. The possibilities range from improvement of existing crops and the
      systematic use of natural diversity through to the domestication of completely
      new species. As examples of possible goals, it is discussed how profiling of
      composition will integrate plant breeding and agronomic practice with emerging
      knowledge about nutrition and health, how improved and novel crops will
      contribute to the creation of new bio-based economies revolving around plant
      products, and how advances in our knowledge about plant-environment and plant
      pathogen interactions will provide novel strategies to stabilize agricultural
      yield in a fluctuating environment and contribute to integrated approaches in
      which modern agriculture is carried out in concert with the environment. In
      addition, knowledge generated by plant science will be needed to monitor,
      understand, and cope with climate change and its impact on agriculture and
      ecosystems. Realization of these goals will require close interactions with
      related disciplines including agronomy and ecology. Further, it will be important
      to continue and deepen open support for research in the developing world.

PMID- 15939734
TI  - Polycyclic aromatic hydrocarbons induce an inflammatory atherosclerotic plaque
      phenotype irrespective of their DNA binding properties.
AB  - Although it has been demonstrated that carcinogenic environmental polycyclic
      aromatic hydrocarbons (PAHs) cause progression of atherosclerosis, the underlying
      mechanism remains unclear. In the present study, we aimed to investigate whether
      DNA binding events are critically involved in the progression of PAH-mediated
      atherogenesis. Apolipoprotein E knockout mice were orally (24 wk, once/wk)
      exposed to 5 mg/kg benzo[a]pyrene (B[a]P), or its nonmutagenic, noncarcinogenic
      structural isoform benzo[e]pyrene (B[e]P). 32P-postlabeling of lung tissue
      confirmed the presence of promutagenic PAH-DNA adducts in B[a]P-exposed animals,
      whereas in B[e]P-exposed and vehicle control animals, these adducts were
      undetectable. Morphometrical analysis showed that both B[a]P and B[e]P caused an
      increase in plaque size, whereas location or number of plaques was unaffected.
      Immunohistochemistry revealed no differences in oxidative DNA damage (8-OHdG) or
      apoptosis in the plaques. Also plasma lipoprotein levels remained unchanged after
      PAH-exposure. However, T lymphocytes were increased > or =2-fold in the plaques
      of B[a]P- and B[e]P-exposed animals. Additionally, B[a]P and to a lesser extent
      B[e]P exposure resulted in increased TGFbeta protein levels in the plaques, that
      was mainly localized in the plaque macrophages. In vitro studies using the murine
      macrophage like RAW264.7 cells showed that inhibition of TGFbeta resulted in
      decreased tumor necrosis factor (TNF) alpha release, suggesting that enhanced
      TGFbeta expression in the plaque macrophages contributes to the proinflammatory
      effects in the vessel wall. In general, this inflammatory reaction in the plaques
      appeared to be a local response since peripheral blood cell composition (T cells,
      B cells, granulocytes, and macrophages) was not changed upon PAH exposure. In
      conclusion, we showed that both B[a]P and B[e]P cause progression of
      atherosclerosis, irrespective of their DNA binding properties. Moreover, our data
      revealed a possible novel mechanism of PAH-mediated atherogenesis, which likely
      involves a TGFbeta-mediated local inflammatory reaction in the vessel wall.

PMID- 15939735
TI  - Calixarene derivative as a tool for highly sensitive detection and oriented
      immobilization of proteins in a microarray format through noncovalent molecular
      interaction.
AB  - One important factor in fabricating protein microarray is to immobilize proteins
      without losing their activity on a solid phase. To keep them functional, it is
      necessary to immobilize proteins in a way that preserve their folded structural
      integrity. In a previous study, we developed novel Calixarene derivatives for the
      immobilization of proteins on the surface of a glass slide (1). In this study, we
      compared the sensitivity and the specificity of the linker molecules with those
      of five other protein attachment agents on glass slides using a prostate-specific
      antigen and its antibodies as a model system. The Calixcrown-coated protein chip
      showed a superior sensitivity and a much lower detection limit than those chips
      prepared by other methods. When we tested the capability of Calixcrown to
      immobilize antibody molecules, it appeared that Calixcrown makes arrangement of
      antibody be more regular with the vertical orientation than the covalent-bond
      agent. We also observed that the Calixcrown chip could be used for the diagnostic
      application with clinical samples from prostate cancer and HIV patients. Finally,
      we applied the Calixcrown chip using an antibody microarray to identify up- or
      down-regulated proteins in specific tissue and detected several up- or down
      regulated proteins from a rat liver by administering toxin. Thus, the Calixcrown
      chip can be used as a powerful tool with a wide range of applications, including
      protein-protein interaction, protein-DNA interaction, and an enzyme activity
      assay.

PMID- 15939736
TI  - IKKbeta-dependent NF-kappaB pathway controls vascular inflammation and intimal
      hyperplasia.
AB  - Nuclear factor-kappaB (NF-kappaB)-mediated vascular inflammation is a prominent
      characteristic of atherogenesis and restenosis. We noted that angioplastic injury
      to carotid artery elicited two phases of NF-kappaB activation characterized by an
      early activation in the arterial media and a late activation coupled with high
      levels of inhibitor of IkappaB kinase (IKK) activity in intima. These findings
      prompted us to elucidate the role for the different phases of NF-kappaB
      activation and IKK in the progress of vascular repair. Our results show that
      blockade of the early NF-kappaB activation by perivascular administration of
      pyrrolidine dithiocarbamate transiently attenuates the expression of
      proinflammatory genes in the injured vessels but does not affect intimal
      formation. Interruption of IKKbeta by overexpressing a dominant-negative IKKbeta
      in the injured artery effectively inhibited the late phase of NF-kappaB
      activation, resulting in down-regulation of inducible nitric oxide synthase,
      tumor necrosis factor alpha, and monocyte chemoattractant protein-1 expression in
      conjunction with a 36% reduction in intima size, albeit with a lack of inhibitory
      effect on the early NF-kappaB activation. Collectively, these findings show that
      the IKKbeta-mediated late-phase NF-kappaB activation contributes to intimal
      hyperplasia and the accompanied vascular inflammatory responses.

PMID- 15939737
TI  - Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune
      inflammation.
AB  - The tryptophan (trp)-catabolizing enzyme indolamine 2,3-dioxygenase (IDO) is
      induced by the T helper 1 (Th 1) cytokine IFN-gamma during infections in various
      tissues including the brain. Recent studies demonstrated an immune modulatory
      function of this enzyme, since IDO-mediated depletion of trp hinders T cell
      proliferation, while its inhibition by 1-methyl-tryptophan (1-Mt) induces
      breakdown of immune tolerance in the placenta, leading to rejection of allogeneic
      concepti. Here, we tested IDO expression and function during experimental
      autoimmune encephalomyelitis (EAE) actively induced in adult SJL mice by
      immunization with PLP139-151. IDO activity (determined by HPLC analysis of the
      kynurenine/tryptophan ratio) was increased in the spleen during the preclinical
      phase, and within the brain and spinal cord at the onset of symptoms.
      Immunocytochemistry revealed macrophages/activated microglia expressing IDO
      during EAE and in vitro experiments confirmed IDO induction in microglia upon IFN
      gamma treatment with synergistic effects of TNF-alpha. Inhibition of IDO by
      systemic administration of 1-Mt at clinical onset significantly exacerbated
      disease scores. From these data, it is tempting to speculate that IFN-gamma from
      encephalitogenic Th 1 cells induces local IDO expression, thereby initiating a
      negative feedback loop which may underlie the self-limitation of autoimmune
      inflammation during EAE and multiple sclerosis.

PMID- 15939738
TI  - Ena/VASP proteins enhance actin polymerization in the presence of barbed end
      capping proteins.
AB  - Ena/VASP proteins influence the organization of actin filament networks within
      lamellipodia and filopodia of migrating cells and in actin comet tails. The
      molecular mechanisms by which Ena/VASP proteins control actin dynamics are
      unknown. We investigated how Ena/VASP proteins regulate actin polymerization at
      actin filament barbed ends in vitro in the presence and absence of barbed end
      capping proteins. Recombinant His-tagged VASP increased the rate of actin
      polymerization in the presence of the barbed end cappers, heterodimeric capping
      protein (CP), CapG, and gelsolin-actin complex. Profilin enhanced the ability of
      VASP to protect barbed ends from capping by CP, and this required interactions of
      profilin with G-actin and VASP. The VASP EVH2 domain was sufficient to protect
      barbed ends from capping, and the F-actin and G-actin binding motifs within EVH2
      were required. Phosphorylation by protein kinase A at sites within the VASP EVH2
      domain regulated anti-capping and F-actin bundling by VASP. We propose that
      Ena/VASP proteins associate at or near actin filament barbed ends, promote actin
      assembly, and restrict the access of barbed end capping proteins.

PMID- 15939739
TI  - Modulation of charge in the phosphate binding site of Escherichia coli ATP
      synthase.
AB  - This paper presents a study of the role of positive charge in the P(i) binding
      site of Escherichia coli ATP synthase, the enzyme responsible for ATP-driven
      proton extrusion and ATP synthesis by oxidative phosphorylation. Arginine
      residues are known to occur with high propensity in P(i) binding sites of
      proteins generally and in the P(i) binding site of the betaE catalytic site of
      ATP synthase specifically. Removal of natural betaArg-246 (betaR246A mutant)
      abrogates P(i) binding; restoration of P(i) binding was achieved by mutagenesis
      of either residue betaAsn-243 or alphaPhe-291 to Arg. Both residues are located
      in the P(i) binding site close to betaArg-246 in x-ray structures. Insertion of
      one extra Arg at beta-243 or alpha-291 in presence of betaArg-246 retained P(i)
      binding, but insertion of two extra Arg, at both positions simultaneously,
      abrogated it. Transition state stabilization was measured using phosphate analogs
      fluoroaluminate and fluoroscandium. Removal of betaArg-246 in betaR246A caused
      almost complete loss of transition state stabilization, but partial rescue was
      achieved in betaN243R/betaR246A and alphaF291R/betaR246A. BetaArg-243 or alphaArg
      291 in presence of betaArg-246 was less effective; the combination of
      alphaF291R/betaN243R with natural betaArg-246 was just as detrimental as
      betaR246A. The data demonstrate that electrostatic interaction is an important
      component of initial P(i) binding in catalytic site betaE and later at the
      transition state complex. However, since none of the mutants showed significant
      function in growth tests, ATP-driven proton pumping, or ATPase activity assays,
      it is apparent that specific stereochemical interactions of catalytic site Arg
      residues are paramount.

PMID- 15939740
TI  - A multifunctional acyl-acyl carrier protein desaturase from Hedera helix L.
      (English ivy) can synthesize 16- and 18-carbon monoene and diene products.
AB  - A desaturase with 83% sequence identity to the coriander delta(4)-16:0-ACP
      desaturase was isolated from developing seeds of Hedera helix (English ivy).
      Expression of the ivy desaturase in Arabidopsis resulted in the accumulation of
      16:1delta(4) and its expected elongation product 18:1delta(6) (petroselinic
      acid). Expression in Escherichia coli resulted in the accumulation of soluble,
      active protein that was purified to apparent homogeneity. In vitro assays
      confirmed delta(4) desaturation with 16:0-ACP; however, with 18:0-acyl acyl
      carrier protein (ACP) desaturation occurred at the delta(9) position. The ivy
      desaturase also converted 16:1delta(9)-ACP and 18:1delta(9)-ACP to the
      corresponding delta(4,9) dienes. These data suggest at least two distinct
      substrate binding modes, one placing C4 at the diiron active site and the other
      placing C9 at the active site. In the latter case, 18:0 would likely bind in an
      extended conformation as described for the castor desaturase with 9-carbons
      accommodated in the cavity beyond the dirron site. However, delta(4) desaturation
      would require the accommodation of 12 carbons for C16 substrates or 14 carbons
      for C18 substrates. The amino acids lining the substrate binding cavity of ivy
      and castor desaturases are conserved except for T117R and P179I (castor/ivy).
      Paradoxically, both substitutions, when introduced into the castor desaturase,
      favored the binding of shorter acyl chains. Thus, it seems likely that delta(4)
      desaturation would require a non-extended, perhaps U-shaped, substrate
      conformation. A cis double bond may facilitate the initiation of such a non
      extended conformation in the monounsaturated substrates. The multifunctional
      properties of the ivy desaturase make it well suited for further dissection of
      the determinants of regiospecificity.

PMID- 15939741
TI  - Evaluation of five antibody detection tests for diagnosis of bovine
      paratuberculosis.
AB  - Five diagnostic tests based on enzyme-linked immunosorbent assay (ELISA)
      technology for bovine paratuberculosis were evaluated by using individual serum
      or milk samples from 359 dairy cattle in seven paratuberculosis-free herds and
      2,094 dairy cattle in seven Mycobacterium paratuberculosis-infected dairy herds.
      Three independent laboratories using three different culture procedures completed
      fecal cultures for M. paratuberculosis on these cattle and found 417 cows to be
      shedding M. paratuberculosis in their feces. An animal that was fecal culture
      positive for M. paratuberculosis by any of the three laboratories was considered
      a confirmed case of infection. The specificity of three ELISAs (two on serum and
      one on milk) was > or =99.8%. The specificity of the remaining two ELISAs, both
      done on serum, was 94.9 and 84.7%. Four of the five ELISAs evaluated produced
      similar sensitivity in detecting fecal culture-positive cattle (27.8 to 28.9%).
      Serum ELISA "D" had the lowest specificity (84.7%) and the highest sensitivity
      (44.5%), but if the cutoff value defining a positive test was changed from 125 to
      250% (of the positive control) the sensitivity and specificity, 31.8 and 97.5%,
      respectively, were comparable to those of the other four assays. If the case
      definition for M. paratuberculosis infection was based on the culture results of
      a single laboratory instead of the combined results of three laboratories, ELISA
      sensitivity estimates were 45.7 to 50.0%. With the exception of ELISA D, assay
      agreement was high (kappa 0.66 to 0.85) for categorical assay interpretations
      (positive or negative), but linear regression of quantitative results showed low
      correlation coefficients (r(2) = 0.40 to 0.68) due to the fact that ELISA results
      for some cows were high in one assay but low in another assay. Likelihood ratio
      analysis showed a direct relationship between the magnitude of ELISA result and
      the odds of a cow shedding M. paratuberculosis in its feces. If used judiciously
      and interpreted quantitatively, these ELISAs are useful tools in support of
      paratuberculosis control programs in dairy herds.

PMID- 15939742
TI  - Lipopolysaccharide-based enzyme-linked immunosorbent assay for experimental use
      in detection of antibodies to Lawsonia intracellularis in pigs.
AB  - An enzyme-linked immunosorbent assay (ELISA) for Lawsonia intracellularis was
      developed and compared with a whole-cell antigen-based immunofluorescence
      antibody test (IFAT). The antigen-containing lipopolysaccharide (LPS) was derived
      from Percoll gradient purified cultures of L. intracellularis by using a
      modification of the Westphal hot phenol procedure. The antigen was bound directly
      to polystyrene 96-well microtiter plates, and the assay was performed in an
      indirect ELISA format. Specificity and sensitivity values based on 80 known
      positive and 80 known negative serum samples from controlled experimental trials
      were 93.7% and 88.7%, respectively. Serological results from a controlled L.
      intracellularis challenge exposure study confirmed the high specificity and
      sensitivity of this assay (100% and 99.5%, respectively). Comparisons between the
      LPS ELISA and the IFAT in detecting anti-Lawsonia antibodies in this controlled
      study revealed significantly more LPS ELISA-positive pigs than IFAT-positive pigs
      on days 21, 28, 35, and 42 (P = 0.003, 0.030, 0.002, and 0.006, respectively).
      This indirect ELISA (LPS ELISA) test is an improved method of detecting
      antibodies in pigs soon after exposure to L. intracellularis, regardless of
      isolate type (vaccine or wild type) in experimental studies. The LPS ELISA may be
      used as a tool to support future research trials on vaccine efficacy and to
      further understand the immune response induced by L. intracellularis.

PMID- 15939743
TI  - Preliminary evaluation of whole-blood gamma interferon release for clinical
      assessment of cellular immunity in patients with active coccidioidomycosis.
AB  - Assessment of the cellular immune response in coccidioidomycosis has
      epidemiologic and prognostic importance. Measurement of delayed-type
      hypersensitivity to skin testing has been used in the past to determine cellular
      immunity in coccidioidomycosis. However, no skin tests are currently available in
      the United States. Assay of gamma interferon (IFN-gamma) release in whole blood
      in response to incubation with antigen has been used to assess cellular immunity
      in tuberculosis. We used a similar assay using the coccidioidal antigen
      preparation T27K to measure the in vitro cellular immune responses among a cohort
      of 69 subjects with active coccidioidomycosis. IFN-gamma release was bimodal,
      with concentrations above and below 5 IU/ml. Using multivariate logistic
      regression, underlying disease and disseminated or chronic pulmonary
      coccidioidomycosis was significantly associated with the release of IFN-gamma at
      a concentration of <5 IU/ml (P = 0.02 or 0.05, respectively). In addition, the
      release IFN-gamma concentration was <5 IU/ml in all subjects with a clinical
      severity score of > or =6 (P = 0.02). The release IFN-gamma concentration
      correlated with expression of CD69 on T lymphocytes in an in vitro assay using
      T27K as the antigen (Spearman's rho = 0.59; P < 0.01). These results suggest that
      the IFN-gamma release assay with T27K as the antigen may be a useful clinical
      test for assessing cellular immunity in patients with active coccidioidomycosis.

PMID- 15939744
TI  - Inhibitory receptors CD85j, LAIR-1, and CD152 down-regulate immunoglobulin and
      cytokine production by human B lymphocytes.
AB  - Class switching consists in the substitution of the heavy-chain constant region
      of immunoglobulin M (IgM) with that of IgG, IgA, or IgE. This enables antibodies
      to acquire new effector functions that are crucial to combat invading pathogens.
      Class switching usually requires engagement of CD40 on B cells by CD40 ligand
      (CD40L) on antigen-activated CD4(+) T cells and the production of cytokines. The
      process must be regulated tightly because abnormal IgG and IgA production favors
      the onset of autoimmunity, whereas increased switching to IgE leads to atopy.
      These inflammatory disorders can be triggered or exacerbated by costimulatory
      signals. Although thoroughly investigated on T cells, the roles of the inhibitory
      receptors CD85j, LAIR-1, and CD152 on B-cell functions have not been fully
      elucidated. In this study we show that cross-linking of the B-cell inhibitory
      receptors by specific monoclonal antibodies inhibits IgG and IgE production,
      reduces the percentage of IgG- and IgE-expressing B cells, and down-regulates
      interleukin 8 (IL-8), IL-10, and tumor necrosis factor alpha production. These
      effects were demonstrated using different B-cell stimulatory pathways (recall
      antigens, CD40L-transfected cells plus IL-4, and lipopolysaccharide plus IL-4).
      It thus appears that CD85j, LAIR-1, and CD152 play a central role for the control
      of IL-4-driven isotype switching.

PMID- 15939745
TI  - Protective antigen and toxin neutralization antibody patterns in anthrax
      vaccinees undergoing serial plasmapheresis.
AB  - Recipients of licensed anthrax vaccine (AVA; Biothrax) could serve as a source of
      hyperimmune plasma and immunoglobulin for therapy and prophylaxis. We measured
      serum antibodies during serial weekly to biweekly plasmapheresis in 38
      individuals previously vaccinated with 4 to 27 doses of AVA. Immunoglobulin G
      (IgG) to protective antigen (PA) and toxin neutralization assay (TNA) antibody
      levels were highly correlated (r = 0.86930 and P < 0.0001 for anti-PA
      concentration versus TNA concentration). Significant decreases in antibody titer
      and concentration were observed over time when compared for the number of days
      from the last AVA injection (P < 0.0001 for both anti-PA and TNA concentration)
      and for the number of days from the first plasmapheresis (P = 0.0007 for anti-PA
      concentration and P = 0.0025 for TNA concentration). The rate of the decrease in
      total IgG concentration (half-life [t(1/2)] = 198.90 days after first
      plasmapheresis) was significantly less than the decrease in anti-PA IgG (t(1/2) =
      63.53 days) (P < 0.0001), indicating that the reduction in anti-PA IgG was more
      likely due to natural decay than plasmapheresis. The time since the last
      injection and the time after initial plasmapheresis are important elements in
      considering an optimal schedule for collecting anthrax hyperimmune plasma. Good
      correlation between IgG to PA and TNA antibodies suggests that the anti-PA enzyme
      linked immunosorbent assay can be used as a high-throughput screen for functional
      immune reactivity in donor plasma units.

PMID- 15939746
TI  - Effects of absorption with pneumococcal type 22F polysaccharide on maternal, cord
      blood, and infant immunoglobulin G antipneumococcal polysaccharide antibodies.
AB  - The aim of this study was to evaluate the effect of absorption with pneumococcal
      type 22F polysaccharide on antipneumococcal antibody titers in unimmunized
      Chilean pregnant women and on antibodies in their offspring at birth and 3, 6,
      and 12 months of age. Sera from 10 healthy pregnant women and from their
      offspring at birth and at 3, 6, and 12 months of age were studied. Immunoglobulin
      G antibodies against serotypes 1, 3, 4, 5, 6B, 9V, 14, 18, 19F, and 23F were
      measured by a standardized enzyme-linked immunosorbent assay method. All sera
      were absorbed with polysaccharide C, and aliquots of each serum were absorbed
      with polysaccharide 22F. Individual results were expressed in mug/ml based on the
      standard serum pool 89-SF. Absorption with polysaccharide 22F reduced antibody
      concentrations in all samples and to all 10 serotypes studied. Reduction was
      highest in maternal sera and in cord blood, but it was also present at 3, 6, and
      12 months of age. The percent reduction ranged from 24% for serotype 14 to 50%
      for serotype 1 in maternal samples and from 20% for serotype 18C to 49% for
      serotype 4 in cord blood samples. The percentages of transplacental transmission
      were similar for nonabsorbed and absorbed maternal fetal pairs. Absorption with
      serotype 22F had a significant impact on antipneumococcal antibody concentrations
      in unimmunized pregnant women and in their offspring. Our results suggest that
      absorption with 22F polysaccharide needs to be performed in studies of
      transplacental transmission of antipneumococcal antibodies.

PMID- 15939747
TI  - Antibody responses in reindeer (Rangifer tarandus) infected with Mycobacterium
      bovis.
AB  - Despite having a very low incidence of disease, reindeer (Rangifer tarandus) are
      subject to tuberculosis (TB) testing requirements for interstate shipment and
      herd accreditation in the United States. Improved TB tests are desperately
      needed, as many reindeer are falsely classified as reactors by current testing
      procedures. Sera collected sequentially from 11 (experimentally) Mycobacterium
      bovis-infected reindeer and 4 noninfected reindeer were evaluated by enzyme
      linked immunosorbent assay (ELISA), immunoblotting, and multiantigen print
      immunoassay (MAPIA) for antibody specific to M. bovis antigens. Specific antibody
      was detected as early as 4 weeks after challenge with M. bovis. By MAPIA, sera
      were tested with 12 native and recombinant antigens, which were used to coat
      nitrocellulose. All M. bovis-infected reindeer developed responses to MPB83 and a
      fusion protein, Acr1/MPB83, and 9/11 had responses to MPB70. Other antigens less
      commonly recognized included MPB59, ESAT-6, and CFP10. Administration of purified
      protein derivatives for skin testing boosted serum antibody responses, as
      detected by each of the assays. Of the noninfected reindeer, 2/4 had responses
      that were detectable immediately following skin testing, which correlated with
      pathological findings (i.e., presence of granulomatous lesions yet the absence of
      acid-fast bacteria). The levels of specific antibody produced by infected
      reindeer appeared to be associated with disease progression but not with cell
      mediated immunity. These findings indicate that M. bovis infection of reindeer
      elicits an antibody response to multiple antigens that can be boosted by skin
      testing. Serological tests using carefully selected specific antigens have
      potential for early detection of infections in reindeer.

PMID- 15939749
TI  - Borreliacidal OspC antibodies specific for a highly conserved epitope are
      immunodominant in human lyme disease and do not occur in mice or hamsters.
AB  - Humans produce highly specific borreliacidal antibodies against outer surface
      protein C (OspC) shortly after infection with Borrelia burgdorferi sensu stricto.
      We previously demonstrated the epitope recognized by immunoglobulin M (IgM) and
      IgG OspC borreliacidal antibodies was located within the 50 amino acids nearest
      the carboxy (C) terminus. In this study, we show the immunodominant epitope is
      located in the highly conserved region within the seven C-terminal amino acids.
      Six early Lyme disease sera that contained borreliacidal activity and IgM and/or
      IgG OspC antibodies were chosen randomly and adsorbed with truncated OspC
      containing the 16 or 7 amino acids nearest the C terminus. Adsorptions with each
      truncated protein abrogated the borreliacidal activity completely. In addition,
      only small concentrations of OspC antibodies remained detectable by enzyme-linked
      immunosorbent assay and Western blotting. Moreover, borreliacidal OspC antibodies
      were not induced in laboratory mice or hamsters despite heavy infections with B.
      burgdorferi spirochetes. These findings confirm that borreliacidal antibodies
      comprise the majority of the IgM and IgG OspC antibody response in human Lyme
      disease and that the epitope is located in the highly conserved C terminus. In
      addition, rodent animal models appear to be inappropriate subjects for assessing
      the effectiveness of the epitope for serodiagnosis or as a human Lyme disease
      vaccine.

PMID- 15939748
TI  - Adoptive immunotherapy of feline immunodeficiency virus with autologous ex vivo
      stimulated lymphoid cells modulates virus and T-cell subsets in blood.
AB  - The potential of immunotherapy with autologous virus-specific T cells to affect
      the course of feline immunodeficiency virus (FIV) infection was explored in a
      group of specific-pathogen-free cats infected with FIV a minimum of 10 months
      earlier. Popliteal lymph node cells were stimulated by cocultivation with UV
      inactivated autologous fibroblasts infected with recombinant vaccinia viruses
      expressing either FIV gag or env gene products, followed by expansion in
      interleukin-2. One or two infusions of both Gag- and Env-stimulated cells
      resulted in a slow increase in FIV-specific gamma interferon-secreting T cells in
      the circulation of cats. In the same animals, viral set points fluctuated widely
      during the first 2 to 3 weeks after adoptive transfer and then returned to
      pretreatment levels. The preexisting viral quasispecies was also found to be
      modulated, whereas no novel viral variants were detected. Circulating CD4(+)
      counts underwent a dramatic decline early after treatment. CD4/CD8 ratios
      remained instead essentially unchanged and eventually improved in some animals.
      In contrast, a single infusion of Gag-stimulated cells alone produced no apparent
      modulations of infection.

PMID- 15939750
TI  - Demonstration of components of antigen 85 complex in cerebrospinal fluid of
      tuberculous meningitis patients.
AB  - Tuberculous meningitis (TBM) is the most common form of chronic infection of the
      central nervous system. Despite the magnitude of the problem, the general
      diagnostic outlook is discouraging. Specifically, there is no generally accepted
      early confirmative diagnosis protocol available for TBM. Various Mycobacterium
      tuberculosis antigens are now recognized as potential markers for diagnosis of
      TBM. However, their presence remains questionable, and many of these antigens are
      reported in the blood but not in the cerebrospinal fluid (CSF). This study
      identifies a specific protein marker in CSF which will be useful in early
      diagnosis of TBM. We have demonstrated the presence of a 30-kDa protein band in
      CSF of 100% (n = 5) of confirmed and 90% (n = 138) of suspected TBM patients out
      of 153 TBM patients. The 30-kDa band was excised from the gel, destained
      extensively, and digested with trypsin. The resulting peptides were analyzed by
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). Partially purified
      proteins from CSF samples of TBM were analyzed by two-dimensional polyacrylamide
      gel electrophoresis and Western blotting. Immunoblotting and enzyme-linked
      immunosorbent assay (ELISA) were performed to confirm the presence of proteins in
      the 30-kDa protein band. The antigen 85 (Ag 85) complex was detected in CSF of
      TBM patients by indirect ELISA using antibodies against Ag 85 complex. The
      results of this study showed the 30-kDa protein band contained MTB proteins
      Rv3804c (Ag85A) and Rv1886c (Ag 85B), both members of the Ag85 complex. This was
      also confirmed by using immunotechniques such as indirect ELISA and the dot
      immunobinding assay. Detection of Ag85 complex was observed in CSF of 89% (71 out
      of 80) of suspected TBM patients that were 30-kDa protein positive. The observed
      30-kDa protein in the CSF is comprised of the MTB Ag85 complex. This protein was
      earlier reported to be present in the blood of patients with extra-central
      nervous system tuberculosis. Therefore, this finding suggests that this protein
      can be used as a molecular marker for any type of tuberculous infection. It also
      provides a more sensitive immunoassay option for the early and confirmatory
      diagnosis of TBM.

PMID- 15939751
TI  - Evaluation of PCR-based assay for diagnosis of spotted fever group rickettsiosis
      in human serum samples.
AB  - A nested PCR assay was developed for the detection of spotted fever group (SFG)
      rickettsiae in serum samples. The assay was based on specific primers derived
      from the rickettsial outer membrane protein B gene (rompB) of Rickettsia conorii.
      An SFG rickettsia-specific signal is obtained from R. akari, R. japonica, R.
      sibirica, and R. conorii. Other bacterial species tested did not generate any
      signal, attesting to the specificity of the assay. As few as seven copies of the
      rompB gene of R. conorii could be detected in 200 microl of serum sample. The
      assay was evaluated with a panel of sera obtained from patients with acute-phase
      febrile disease tested by immunofluorescent antibody assay (IFA). The SFG
      rickettsia-specific DNA fragment was detected in 71 out of 100 sera, which were
      proven to have immunoglobulin M antibodies against SFG rickettsial antigen by
      IFA. The results were further confirmed by restriction fragment length
      polymorphism and sequencing analysis of the DNA fragments. The results indicated
      that this PCR assay is suitable for the diagnosis of spotted fever group
      rickettsiosis in Korea.

PMID- 15939752
TI  - Antibody response to actinomyces antigen and dental caries experience:
      implications for caries susceptibility.
AB  - Fluoridated dentifrices reduce dental caries in subjects who perform effective
      oral hygiene. Actinomyces naeslundii increases in teeth-adherent microbial
      biofilms (plaques) in these subjects, and a well-characterized serum
      immunoglobulin G (IgG) antibody response (Actinomyces antibody [A-Ab]) is also
      increased. Other studies suggest that a serum IgG antibody response to
      streptococcal d-alanyl poly(glycerophosphate) (S-Ab) may indicate caries
      experience associated strongly with gingival health and exposure to fluoridated
      water. The aim of this study was to investigate relationships between A-Ab
      response, oral hygiene, S-Ab response, and caries experience. Measurements were
      made of A-Ab and S-Ab concentrations, caries experience (number of decayed,
      missing, and filled teeth [DMFT], number of teeth surfaces [DMFS], and number of
      decayed teeth needing treated [DT]), exposure to fluoridated water (Flu), mean
      clinical pocket depth (PD; in millimeters), and extent of plaque (PL) and
      gingival bleeding on probing (BOP). A-Ab concentration, the dependent variable in
      a multiple regression analysis, increased with S-Ab concentration and decreased
      with PL and DMFT adjusted for Flu (R(2) = 0.51, P < 0.002). Residual associations
      with age, DMFS, DT, and BOP were not significant. In addition, an elevated A-Ab
      response, defined from immunoprecipitation and immunoassay measurements,
      indicated a significant, 30% reduction in DMFT after adjustment for significant
      age and Flu covariance (analysis of variance with covariance F statistic = 10.6,
      P < 0.003; S-Ab response and interactions not significant). Thus, an elevated A
      Ab response indicates less caries in subjects performing effective oral hygiene
      using fluoridated dentifrices. Conversely, a low A-Ab response is suggestive of
      decreased A. naeslundii binding to saliva-coated apatite and greater caries
      experience, as reported by others.

PMID- 15939753
TI  - Antibody responses to recombinant protein fragments of the major outer membrane
      protein and polymorphic outer membrane protein POMP90 in Chlamydophila abortus
      infected pregnant sheep.
AB  - Chlamydophila abortus is one of the major causes of infectious abortion in
      pregnant sheep (enzootic abortion of ewes or EAE) worldwide. Organisms shed in
      infected placentas and uterine discharges at lambing time are the main sources of
      environmental contamination, responsible for transmission to susceptible animals
      and possible human contacts. In the present study, a recently developed test,
      based on a recombinant fragment of the polymorphic outer membrane protein POMP90
      (rOMP90-4 indirect enzyme-linked immunosorbent assay [iELISA]) and one based on
      the variable segment 2 (VS2) region of the major outer membrane protein (MOMP)
      (MOMP VS2 iELISA) were compared using sera from C. abortus-infected ewes at
      different stages throughout pregnancy. The rOMP90 iELISA detected antibody much
      earlier in pregnancy than the MOMP iELISA, which, like the complement fixation
      test, detected antibody only at the time of abortion or lambing. No anti-MOMP
      antibody response could be detected in three of seven experimentally infected
      ewes. Furthermore, the rOMP90 iELISA detected antibody in an animal that
      seroconverted during the course of the study, which the MOMP iELISA failed to
      detect. Overall, the results show that the rOMP90-4 iELISA is considerably more
      sensitive than the MOMP VS2 iELISA for identifying animals infected with C.
      abortus. Earlier detection of infection will allow appropriate control measures
      to be taken to reduce environmental contamination, thus limiting the spread of
      infection, financial losses, and the possible risks of zoonotic transmission to
      humans.

PMID- 15939754
TI  - Several recombinant capsid proteins of equine rhinitis a virus show potential as
      diagnostic antigens.
AB  - Equine rhinitis A virus (ERAV) is a significant pathogen of horses and is also
      closely related to Foot-and-mouth disease virus (FMDV). Despite these facts,
      knowledge of the prevalence and importance of ERAV infections remains limited,
      largely due to the absence of a simple, robust diagnostic assay. In this study,
      we compared the antigenicities of recombinant full-length and fragmented ERAV
      capsid proteins expressed in Escherichia coli by using sera from experimentally
      infected and naturally exposed horses. We found that, from the range of antigens
      tested, recombinant proteins encompassing the C-terminal region of VP1, full
      length VP2, and the N-terminal region of VP2 reacted specifically with antibodies
      present in sera from each of the five experimentally infected horses examined.
      Antibodies to epitopes on VP2 (both native and recombinant forms) persisted
      longer postinfection (>105 days) than antibodies specific for epitopes on other
      fragments. Our data also suggest that B-cell epitopes within the C terminus of
      VP1 and N terminus of VP2 contribute to a large proportion of the total
      reactivity of recombinant VP1 and VP2, respectively. Importantly, the reactivity
      of these VP1 and VP2 recombinant proteins in enzyme-linked immunosorbent assays
      (ELISAs) correlated well with the results from a range of native antigen-based
      serological assays using sera from 12 field horses. This study provides promising
      candidates for development of a diagnostic ERAV ELISA.

PMID- 15939755
TI  - CD4(+) CD25(+) T cells prevent arthritis associated with Borrelia vaccination and
      infection.
AB  - CD4(+) CD25(+) T cells are a population of regulatory T cells associated with
      control of arthritis in anti-interleukin-17 antibody-treated Borrelia-vaccinated
      and challenged gamma interferon-deficient mice. Here, we present direct evidence
      that adoptive transfer of enriched CD4(+) CD25(+) T cells from these mice can
      prevent the development of arthritis in Borrelia-vaccinated and challenged mice.
      These findings establish a major role for CD4(+) CD25(+) T cells in the
      prevention of arthritis in Borrelia-vaccinated and challenged animals.

PMID- 15939756
TI  - Opsonization effects on Mycobacterium avium subsp. paratuberculosis--macrophage
      interactions.
AB  - High antibody titers in ruminants infected with Mycobacterium avium subsp.
      paratuberculosis correlates with disease progression. Effects of humoral
      responses during mycobacterial infection are not completely understood. This
      study suggests that activation status may be an important factor in determining
      macrophage ability to limit proliferation of opsonized M. avium subsp.
      paratuberculosis.

PMID- 15939757
TI  - Surface envelope glycoprotein is B-lymphocyte immunodominant in sheep naturally
      infected with ovine progressive pneumonia virus.
AB  - The B-lymphocyte-immunodominant antigen involved in naturally ovine progressive
      pneumonia virus (OPPV)-infected mature sheep remains unknown. Therefore, the
      amount of antibody in sera from 10 naturally OPPV-infected sheep was evaluated by
      immunoprecipitation (IP) of the major viral proteins in
      [(35)S]methionine/cysteine-labeled OPPV (whole virus) lysate. Using an excess of
      OPPV proteins in whole-virus lysate, 8 out of 10 sheep had the highest serum
      antibody IP endpoint titers to the gp135 surface envelope glycoprotein (SU).
      Also, 2 out of 10 sheep had equivalent serum antibody IP endpoint titers to the
      transmembrane glycoprotein oligomer (TM90) and SU. Since these data indicate that
      SU is the immunodominant protein in most mature sheep persistently infected with
      OPPV, SU-specific diagnostic serological assays can be utilized for OPPV
      diagnosis.

PMID- 15939758
TI  - Physiological regulation of yeast cell death in multicellular colonies is
      triggered by ammonia.
AB  - The existence of programmed cell death (PCD) in yeast and its significance to
      simple unicellular organisms is still questioned. However, such doubts usually do
      not reflect the fact that microorganisms in nature exist predominantly within
      structured, multicellular communities capable of differentiation, in which a
      profit of individual cells is subordinated to a profit of populations. In this
      study, we show that some PCD features naturally appear during the development of
      multicellular Saccharomyces cerevisiae colonies. An ammonia signal emitted by
      aging colonies triggers metabolic changes that localize yeast death only in the
      colony center. The remaining population can exploit the released nutrients and
      survives. In colonies defective in Sok2p transcription factor that are unable to
      produce ammonia, death is spread throughout the whole population, thus decreasing
      the lifetime of the colony. The absence of Mca1p metacaspase or Aif1p orthologue
      of mammalian apoptosis-inducing factor does not prevent regulated death in yeast
      colonies.

PMID- 15939759
TI  - De novo formation of basal bodies in Naegleria gruberi: regulation by
      phosphorylation.
AB  - The de novo formation of basal bodies in Naegleria gruberi was preceded by the
      transient formation of a microtubule (MT)-nucleating complex containing gamma
      tubulin, pericentrin, and myosin II complex (GPM complex). The MT-nucleating
      activity of GPM complexes was maximal just before the formation of visible basal
      bodies and then rapidly decreased. The regulation of MT-nucleating activity of
      GPM complexes was accomplished by a transient phosphorylation of the complex.
      Inhibition of dephosphorylation after the formation of basal bodies resulted in
      the formation of multiple flagella. 2D-gel electrophoresis and Western blotting
      showed a parallel relationship between the MT-nucleating activity of GPM
      complexes and the presence of hyperphosphorylated gamma-tubulin in the complexes.
      These data suggest that the nucleation of MTs by GPM complexes precedes the de
      novo formation of basal bodies and that the regulation of MT-nucleating activity
      of GPM complexes is essential to the regulation of basal body number.

PMID- 15939760
TI  - Methyl CpG-binding proteins induce large-scale chromatin reorganization during
      terminal differentiation.
AB  - Pericentric heterochromatin plays an important role in epigenetic gene
      regulation. We show that pericentric heterochromatin aggregates during myogenic
      differentiation. This clustering leads to the formation of large chromocenters
      and correlates with increased levels of the methyl CpG-binding protein MeCP2 and
      pericentric DNA methylation. Ectopic expression of fluorescently tagged MeCP2
      mimicked this effect, causing a dose-dependent clustering of chromocenters in the
      absence of differentiation. MeCP2-induced rearrangement of heterochromatin
      occurred throughout interphase, did not depend on the H3K9 histone methylation
      pathway, and required the methyl CpG-binding domain (MBD) only. Similar to MeCP2,
      another methyl CpG-binding protein, MBD2, also increased during myogenic
      differentiation and could induce clustering of pericentric regions, arguing for
      functional redundancy. This MeCP2- and MBD2-mediated chromatin reorganization may
      thus represent a molecular link between nuclear genome topology and the
      epigenetic maintenance of cellular differentiation.

PMID- 15939761
TI  - ADAR2-mediated editing of RNA substrates in the nucleolus is inhibited by C/D
      small nucleolar RNAs.
AB  - Posttranscriptional, site-specific adenosine to inosine (A-to-I) base
      conversions, designated as RNA editing, play significant roles in generating
      diversity of gene expression. However, little is known about how and in which
      cellular compartments RNA editing is controlled. Interestingly, the two enzymes
      that catalyze RNA editing, adenosine deaminases that act on RNA (ADAR) 1 and 2,
      have recently been demonstrated to dynamically associate with the nucleolus.
      Moreover, we have identified a brain-specific small RNA, termed MBII-52, which
      was predicted to function as a nucleolar C/D RNA, thereby targeting an A-to-I
      editing site (C-site) within the 5-HT2C serotonin receptor pre-mRNA for 2'-O
      methylation. Through the subcellular targeting of minigenes that contain natural
      editing sites, we show that ADAR2- but not ADAR1-mediated RNA editing occurs in
      the nucleolus. We also demonstrate that MBII-52 forms a bona fide small nucleolar
      ribonucleoprotein particle that specifically decreases the efficiency of RNA
      editing by ADAR2 at the targeted C-site. Our data are consistent with a model in
      which C/D small nucleolar RNA might play a role in the regulation of RNA editing.

PMID- 15939762
TI  - A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross
      talk with EGFR in prostate cancer cells.
AB  - The bioactive phospholipids, lysophosphatidic acid (LPA) and phosphatidic acid
      (PA), regulate pivotal processes related to the pathogenesis of cancer. Here, we
      report characterization of a novel lipid kinase, designated acylglycerol kinase
      (AGK), that phosphorylates monoacylglycerol and diacylglycerol to form LPA and
      PA, respectively. Confocal microscopy and subcellular fractionation suggest that
      AGK is localized to the mitochondria. AGK expression was up-regulated in prostate
      cancers compared with normal prostate tissues from the same patient. Expression
      of AGK in PC-3 prostate cancer cells markedly increased formation and secretion
      of LPA. This increase resulted in concomitant transactivation of the EGF receptor
      and sustained activation of extracellular signal related kinase (ERK) 1/2,
      culminating in enhanced cell proliferation. AGK expression also increased
      migratory responses. Conversely, down-regulating expression of endogenous AGK
      inhibited EGF- but not LPA-induced ERK1/2 activation and progression through the
      S phase of the cell cycle. Hence, AGK can amplify EGF signaling pathways and may
      play an important role in the pathophysiology of prostate cancer.

PMID- 15939763
TI  - {alpha}-Syntrophin regulates ARMS localization at the neuromuscular junction and
      enhances EphA4 signaling in an ARMS-dependent manner.
AB  - EphA4 signaling has recently been implicated in the regulation of synapse
      formation and plasticity. In this study, we show that ankyrin repeat-rich
      membrane spanning (ARMS; also known as a kinase D-interacting substrate of 220
      kD), a substrate for ephrin and neurotrophin receptors, was expressed in
      developing muscle and was concentrated at the neuromuscular junction (NMJ). Using
      yeast two-hybrid screening, we identified a PDZ (PSD-95, Dlg, ZO-1) domain
      protein, alpha-syntrophin, as an ARMS-interacting protein in muscle.
      Overexpression of alpha-syntrophin induced ARMS clustering in a PDZ domain
      dependent manner. Coexpression of ARMS enhanced EphA4 signaling, which was
      further augmented by the presence of alpha-syntrophin. Moreover, the ephrin-A1
      induced tyrosine phosphorylation of EphA4 was reduced in C2C12 myotubes after the
      blockade of ARMS and alpha-syntrophin expression by RNA interference. Finally,
      alpha-syntrophin-null mice exhibited a disrupted localization of ARMS and EphA4
      at the NMJ and a reduced expression of ARMS in muscle. Altogether, our findings
      suggest that ARMS may play an important role in regulating postsynaptic signal
      transduction through the syntrophin-mediated localization of receptor tyrosine
      kinases such as EphA4.

PMID- 15939764
TI  - Regulation of stroke and glide in a foot-propelled avian diver.
AB  - Bottom-feeding, breath-hold divers would be expected to minimize transit time
      between the surface and foraging depth, thus maximizing the opportunities for
      prey capture during the bottom phase of the dive. To achieve this they can
      potentially adjust a variety of dive parameters, including dive angle and swim
      speed. However, because of predictable changes in buoyancy with depth,
      individuals would also be expected to adjust dive behavior according to dive
      depth. To test these predictions we deployed miniature, dorsally attached data
      loggers that recorded surge and heave accelerations at 64 Hz to obtain the first
      detailed measurements of a foot-propelled diving bird, the European shag
      Phalacrocorax aristotelis, in the wild. The results were used to investigate
      biomechanical changes during the descent, ascent and bottom phases for dives
      varying between 7 m and 43 m deep. Shags descended and ascended almost vertically
      (60-90 degrees relative to the sea surface). During descent, swim speed varied
      between 1.2-1.8 m s(-1) and the frequency of the foot stroke used for propulsion
      decreased significantly with depth, mainly due to a fivefold increase in the
      duration of the glide between strokes. Birds appeared to maintain the duration
      and the maximum strength of power stroke and thus optimize muscle contraction
      efficiency.

PMID- 15939765
TI  - Beta-adrenergic control of plasma glucose and free fatty acid levels in the air
      breathing African catfish Clarias gariepinus Burchell 1822.
AB  - In several water-breathing fish species, beta-adrenergic receptor stimulation by
      noradrenaline leads to a decrease in plasma free fatty acid (FFA) levels, as
      opposed to an increase in air-breathing mammals. We hypothesised that this change
      in adrenergic control is related to the mode of breathing. Therefore, cannulated
      air-breathing African catfish were infused for 90 min with noradrenaline or with
      the nonselective beta-agonist, isoprenaline. To identify the receptor type
      involved, a bolus of either a selective beta1-antagonist (atenolol) or a
      selective beta2-antagonist (ICI 118,551) was injected 15 min prior to the
      isoprenaline infusion. Both noradrenaline and isoprenaline led to an expected
      rise in glucose concentration. Isoprenaline combined with both the beta1- and
      beta2-antagonist led to higher glucose concentrations than isoprenaline alone.
      This could indicate the presence of a stimulatory beta-adrenoceptor different
      from beta1 and beta2-adrenoceptors; these two receptors thus seemed to mediate a
      reduction in plasma glucose concentration. Both noradrenaline and isoprenaline
      led to a significant decrease in FFA concentration. Whereas the beta1-antagonist
      had no effect, the beta2-antagonist reduced the decrease in FFA concentration,
      indicating the involvement of beta2-adrenoceptors. It is concluded that the air
      breathing African catfish reflects water-breathing fish in the adrenergic control
      of plasma FFA and glucose levels.

PMID- 15939766
TI  - Specificity of the fluorescein transport process in Malpighian tubules of the
      cricket Acheta domesticus.
AB  - We demonstrate the presence of an efficient, multispecific transport system for
      excretion of organic anions in the Malpighian tubules of the cricket Acheta
      domesticus using fluorescein (FL) as a model substrate. Malpighian tubules
      rapidly accumulated FL via a high affinity process (Km = 7.75 micromol l(-1));
      uptake was completely eliminated by the prototypical organic anion transport
      inhibitor probenecid (1 mmol l(-1)), but not by p-aminohippuric acid (3 mmol l(
      1)). FL uptake was inhibited by monocarboxylic acids at a high concentration (3
      mmol l(-1)), and inhibition was more effective with an increase in the carbon
      chain of the monocarboxylic acid (37% inhibition by 5-carbon valeric acid, and
      89% inhibition by 7-carbon caprylic acid). Likewise, tests using a series of
      aliphatic glutathione conjugates indicated that only the compound with the
      longest side-chain (decyl-glutathione) significantly inhibited FL uptake (81%
      inhibition). FL uptake was inhibited by a number of xenobiotics, including a
      plant alkaloid (quinine), herbicides (2,4-dichlorophenoxyacetic acid and 4-(2,4
      dichlorophenoxy)-butyric acid), and the insecticide metabolites malathion
      monocarboxylic acid (MMA) and 3-phenoxybenzoic acid (PBA), suggesting that this
      transport system plays an active role in excretion of xenobiotics from Acheta by
      Malpighian tubules. HPLC quantification of MMA and PBA accumulation into
      Malpighian tubules verified that MMA accumulation was via a mediated transport
      process, but suggested that PBA accumulation was by nonspecific binding. The
      presence of a transport system in Malpighian tubules that handles at least one
      pesticide metabolite (MMA) suggests that transport processes could be a mechanism
      conferring resistance to xenobiotic exposure in insects.

PMID- 15939767
TI  - The behavioural transition from straight to curve walking: kinetics of leg
      movement parameters and the initiation of turning.
AB  - The control of locomotion requires the ability to adapt movement sequences to the
      behavioural context of the animal. In hexapod walking, adaptive behavioural
      transitions require orchestration of at least 18 leg joints and twice as many
      muscle groups. Although kinematics of locomotion has been studied in several
      arthropod species and in a range of different behaviours, almost nothing is known
      about the transition from one behavioural state to another. Implicitly, most
      studies on context-dependency assume that all parameters that undergo a change
      during a behavioural transition do so at the same rate. The present study tests
      this assumption by analysing the sequence of kinematic events during turning of
      the stick insect Carausius morosus, and by measuring how the time courses of the
      changing parameters differ between legs. Turning was triggered reliably at a
      known instant in time by means of the optomotor response to large-field visual
      motion. Thus, knowing the start point of the transition, the kinematic parameters
      that initiate turning could be ranked according to their time constants.
      Kinematics of stick insect walking vary considerably among trials and within
      trials. As a consequence, the behavioural states of straight walking and curve
      walking are described by the distributions of 13 kinematic parameters per leg and
      of orientation angles of head and antennae. The transitions between the
      behavioural states are then characterised by the fraction of the variance within
      states by which these distributions differ, and by the rate of change of the
      corresponding time courses. The antennal optomotor response leads that of the
      locomotor system. Visually elicited turning is shown to be initiated by stance
      direction changes of both front legs. The transition from straight to curve
      walking in stick insects follows different time courses for different legs, with
      time constants of kinematic parameters ranging from 1.7 s to more than 3 s.
      Therefore, turning is a behavioural transition that involves a characteristic
      orchestration of events rather than synchronous parallel actions with a single
      time constant.

PMID- 15939768
TI  - Context-dependent changes in strength and efficacy of leg coordination
      mechanisms.
AB  - Appropriate coordination of stepping in adjacent legs is crucial for stable
      walking. Several leg coordination rules have been derived from behavioural
      experiments on walking insects, some of which also apply to arthropods with more
      than six legs and to four-legged walking vertebrates. Three of these rules affect
      the timing of stance-swing transition [rules 1 to 3 (sensu Cruse)]. They can give
      rise to normal leg coordination and adaptive responses to disturbances, as shown
      by kinematic simulations and dynamic hardware tests. In spite of their importance
      to the study of animal walking, the coupling strength associated with these rules
      has never been measured experimentally. Generally coupling strength of the
      underlying mechanisms has been considered constant rather than context-dependent.
      The present study analyses stepping patterns of the stick insect Carausius
      morosus during straight and curve walking sequences. To infer strength and
      efficacy of coupling between pairs of sender and receiver legs, the likelihood of
      the receiver leg being in swing is determined, given a certain delay relative to
      the time of a swing-stance (or stance-swing) transition in the sender leg. This
      is compared to a corresponding measure for independent, hence uncoupled, step
      sequences. The difference is defined as coupling strength. The ratio of coupling
      strength and its theoretical maximum is defined as efficacy. Irrespective of the
      coordination rule, coupling strength between ipsilateral leg pairs is at least
      twice that of contralateral leg pairs, being strongest between ipsilateral hind
      and middle legs and weakest between contralateral middle legs. Efficacy is
      highest for inhibitory rule 1, reaching 84-95% for ipsilateral and 29-65% for
      contralateral leg pairs. Efficacy of excitatory rules 2 and 3 ranges between 35
      56% for ipsilateral and 8-21% for contralateral leg pairs. The behavioural
      transition from straight to curve walking is associated with context-dependent
      changes in coupling strength, increasing in both outer leg pairs and decreasing
      between inner hind and middle leg. Thus, the coordination rules that are thought
      to underlie many adaptive properties of the walking system, themselves adapt in a
      context-dependent manner.

PMID- 15939769
TI  - Digestive state influences the heart rate hysteresis and rates of heat exchange
      in the varanid lizard Varanus rosenbergi.
AB  - To maximize the period where body temperature (Tb) exceeds ambient temperature
      (Ta), many reptiles have been reported to regulate heart rate (fH) and peripheral
      blood flow so that the rate of heat gain in a warming environment occurs more
      rapidly than the rate of heat loss in a cooling environment. It may be
      hypothesized that the rate of cooling, particularly at relatively cool Tbs, would
      be further reduced during postprandial periods when specific dynamic action (SDA)
      increases endogenous heat production (i.e. the heat increment of feeding).
      Furthermore, it may also be hypothesized that the increased perfusion of the
      gastrointestinal organs that occurs during digestion may limit peripheral blood
      flow and thus compromise the rate of heating. Finally, if the changes in fh are
      solely for the purpose of thermoregulation, there should be no associated changes
      in energy demand and, consequently, no hysteresis in the rate of oxygen
      consumption (V(O2)). To test these hypotheses, seven individual Varanus
      rosenbergi were heated and cooled between 19 degrees C and 35 degrees C following
      at least 8 days fasting and then approximately 25 h after consumption of a meal
      (mean 10% of fasted body mass). For a given Tb between the range of 19-35 degrees
      C, fh of fasting lizards was higher during heating than during cooling.
      Postprandial lizards also displayed a hysteresis in fh, although the magnitude
      was reduced in comparison with that of fasting lizards as a result of a higher fh
      during cooling in postprandial animals. Both for fasting and postprandial
      lizards, there was no hysteresis in V(O2) at any Tb throughout the range
      although, as a result of SDA, postprandial animals displayed a significantly
      higher V(O2) than fasting animals both during heating and during cooling at Tbs
      above 24 degrees C. The values of fh during heating at a given Tb were the same
      for fasting and postprandial animals, which, in combination with a slower rate of
      heating in postprandial animals, suggests that a prioritization of blood flow to
      the gastrointestinal organs during digestion is occurring at the expense of
      higher rates of heating. Additionally, postprandial lizards took longer to cool
      at Tbs below 23 degrees C, suggesting that the endogenous heat produced during
      digestion temporarily enhances thermoregulatory ability at lower temperatures,
      which would presumably assist V. rosenbergi during cooler periods in the natural
      environment by augmenting temperature-dependent physiological processes.

PMID- 15939770
TI  - The tube feet of sea urchins and sea stars contain functionally different mutable
      collagenous tissues.
AB  - Echinoderms possess mutable collagenous tissues (MCTs), which are capable of
      undergoing rapid changes in their passive mechanical properties mediated by
      secretions from a specific cell type, the juxtaligamental cell. In this study,
      the possible presence of MCTs in the tube feet of the echinoid Paracentrotus
      lividus and the asteroid Marthasterias glacialis was investigated by measuring
      their extensibility, tensile strength, stiffness and toughness after different
      treatments known to influence the physiological state of MCTs. Calcium removal
      reversibly induced a significant plasticization of the tube feet of both species.
      When exposed to cell-disrupting solutions, the tube foot stem of sea urchins and
      sea stars showed a significant increase in strength, stiffness and toughness in
      the absence of calcium. This response, combined with the ultrastructural
      observation of juxtaligamental-like cells in the connective tissue, confirms that
      an MCT is present in both echinoid and asteroid tube feet. It was observed,
      however, that the tube foot stems of P. lividus and M. glacialis are affected
      differently by exposure to cell-disrupting solutions in the presence of calcium,
      indicating that their MCTs could be functionally different. In their soft state,
      MCTs could assist the muscles in tube foot protraction, bending and retraction;
      in their stiff state, they could play a role in the energy-sparing maintenance of
      position; for example, during strong attachment to the substratum to resist
      hydrodynamically generated loads.

PMID- 15939771
TI  - The mechanical scaling of coasting in zebrafish (Danio rerio).
AB  - Many fish species span two or three orders of magnitude in length during the
      growth from larvae to adults, and this change may have dramatic consequences for
      locomotor performance. We measured how the performance of coasting changes over
      the life history of zebrafish (Danio rerio) and examined the scaling of mechanics
      underlying this change. Adult zebrafish coast disproportionately further and
      faster and maintain their speed for a longer duration than do larvae and
      juveniles. Measurements of drag on tethered dead fish suggest that adult fish
      operate in an inertial regime by coasting at relatively high Reynolds numbers (Re
      > 1000), and in vivo drag measurements showed adults to operate with a drag
      coefficient (Cinert approximately 0.024) that was consistent with previously
      published estimates. However, drag scaled differently at lower Re values than
      those assumed in previous studies. We found a viscous regime at Re < 300, which
      corresponds to the routine coasting of larvae and juveniles. Despite these
      changes in hydrodynamics over growth, a mathematical model of coasting mechanics
      suggests that the disproportionately longer coasting of adults is caused
      primarily by their large body mass and high speed at the beginning of coasting.
      We therefore propose that changes in coasting performance with growth are
      dictated primarily by the scaling of momentum rather than resulting from
      hydrodynamic changes. These results provide an opportunity for new
      interpretations of function in the growth and evolution of fish.

PMID- 15939772
TI  - The aerodynamics of hovering flight in Drosophila.
AB  - Using 3D infrared high-speed video, we captured the continuous wing and body
      kinematics of free-flying fruit flies, Drosophila melanogaster, during hovering
      and slow forward flight. We then 'replayed' the wing kinematics on a dynamically
      scaled robotic model to measure the aerodynamic forces produced by the wings.
      Hovering animals generate a U-shaped wing trajectory, in which large drag forces
      during a downward plunge at the start of each stroke create peak vertical forces.
      Quasi-steady mechanisms could account for nearly all of the mean measured force
      required to hover, although temporal discrepancies between instantaneous measured
      forces and model predictions indicate that unsteady mechanisms also play a
      significant role. We analyzed the requirements for hovering from an analysis of
      the time history of forces and moments in all six degrees of freedom. The wing
      kinematics necessary to generate sufficient lift are highly constrained by the
      requirement to balance thrust and pitch torque over the stroke cycle. We also
      compare the wing motion and aerodynamic forces of free and tethered flies.
      Tethering causes a strong distortion of the stroke pattern that results in a
      reduction of translational forces and a prominent nose-down pitch moment. The
      stereotyped distortion under tethered conditions is most likely due to a
      disruption of sensory feedback. Finally, we calculated flight power based
      directly on the measurements of wing motion and aerodynamic forces, which yielded
      a higher estimate of muscle power during free hovering flight than prior
      estimates based on time-averaged parameters. This discrepancy is mostly due to a
      two- to threefold underestimate of the mean profile drag coefficient in prior
      studies. We also compared our values with the predictions of the same time
      averaged models using more accurate kinematic and aerodynamic input parameters
      based on our high-speed videography measurements. In this case, the time-averaged
      models tended to overestimate flight costs.

PMID- 15939773
TI  - Cuvier's beaked whale (Ziphius cavirostris) head tissues: physical properties and
      CT imaging.
AB  - Tissue physical properties from a Cuvier's beaked whale (Ziphius cavirostris)
      neonate head are reported and compared with computed tomography (CT) X-ray
      imaging. Physical properties measured include longitudinal sound velocity,
      density, elastic modulus and hysteresis. Tissues were classified by type as
      follows: mandibular acoustic fat, mandibular blubber, forehead acoustic fat
      (melon), forehead blubber, muscle and connective tissue. Results show that each
      class of tissues has unique, co-varying physical properties. The mandibular
      acoustic fats had minimal values for sound speed (1350+/-10.6 m s(-1)) and mass
      density (890+/-23 kg m(-3)). These values increased through mandibular blubber
      (1376+/-13 m s(-1), 919+/-13 kg m(-3)), melon (1382+/-23 m s(-1), 937+/-17 kg m(
      3)), forehead blubber (1401+/-7.8 m s(-1), 935+/-25 kg m(-3)) and muscle (1517+/
      46.8 m s(-1), 993+/-58 kg m(-3)). Connective tissue had the greatest mean sound
      speed and density (1628+/-48.7 m s(-1), 1087+/-41 kg m(-3)). The melon formed a
      low-density, low-sound-speed core, supporting its function as a sound focusing
      organ. Hounsfield unit (HU) values from CT X-ray imaging are correlated with
      density and sound speed values, allowing HU values to be used to predict these
      physical properties. Blubber and connective tissues have a higher elastic modulus
      than acoustic fats and melon, suggesting more collagen structure in blubber and
      connective tissues. Blubber tissue elastic modulus is nonlinear with varying
      stress, becoming more incompressible as stress is increased. These data provide
      important physical properties required to construct models of the sound
      generation and reception mechanisms in Ziphius cavirostris heads, as well as
      models of their interaction with anthropogenic sound.

PMID- 15939774
TI  - Effect of an increase in gravity on the power output and the rebound of the body
      in human running.
AB  - The effect of an increase in gravity on the mechanics of running has been studied
      by using a force platform fixed to the floor of an aircraft undergoing flight
      profiles, resulting in a simulated gravity of 1.3 g. The power spent to maintain
      the motion of the centre of mass of the body is approximately 1.3 times greater
      than on Earth, due to a similar increase of both the power spent against gravity
      and to sustain the forward speed changes. This indicates that the average
      vertical displacement per unit distance and the average direction of the push are
      unchanged. The increase in power is mainly due to an increase in step frequency
      rather than to an increase in the work done at each step. The increase in step
      frequency in turn is mainly due to a decreased duration of the effective aerial
      phase (when the vertical force is less than body weight), rather than an increase
      in the stiffness of the bouncing system. The maximal speed where step frequency
      can match the resonant frequency of the bouncing system is increased by
      approximately 5 km h(-1) at 1.3 g. These results suggest a similar running
      mechanics at higher gravity, maintained at the expense of greater energy
      expenditure.

PMID- 15939775
TI  - Molecular characterization and expression of the UV opsin in bumblebees: three
      ommatidial subtypes in the retina and a new photoreceptor organ in the lamina.
AB  - Ultraviolet-sensitive photoreceptors have been shown to be important for a
      variety of visual tasks performed by bees, such as orientation, color and
      polarization vision, yet little is known about their spatial distribution in the
      compound eye or optic lobe. We cloned and sequenced a UV opsin mRNA transcript
      from Bombus impatiens head-specific cDNA and, using western blot analysis,
      detected an eye protein band of approximately 41 kDa, corresponding to the
      predicted molecular mass of the encoded opsin. We then characterized UV opsin
      expression in the retina, ocelli and brain using immunocytochemistry. In the main
      retina, we found three different ommatidial types with respect to the number of
      UV opsin-expressing photoreceptor cells, namely ommatidia containing two, one or
      no UV opsin-immunoreactive cells. We also observed UV opsin expression in the
      ocelli. These results indicate that the cloned opsin probably encodes the P350 nm
      pigment, which was previously characterized by physiological recordings.
      Surprisingly, in addition to expression in the retina and ocelli, we found opsin
      expression in different parts of the brain. UV opsin immunoreactivity was
      detected in the proximal rim of the lamina adjacent to the first optic chiasm,
      which is where studies in other insects have found expression of proteins
      involved in the circadian clock, period and cryptochrome. We also found UV opsin
      immunoreactivity in the core region of the antennal lobe glomeruli and different
      clusters of perikarya within the protocerebrum, indicating a putative function of
      these brain regions, together with the lamina organ, in the entrainment of
      circadian rhythms. In order to test for a possible overlap of clock protein and
      UV opsin spatial expression, we also examined the expression of the period
      protein in these regions.

PMID- 15939777
TI  - Patterns of red muscle strain/activation and body kinematics during steady
      swimming in a lamnid shark, the shortfin mako (Isurus oxyrinchus).
AB  - The dynamics of steady swimming were examined in the shortfin mako (Isurus
      oxyrinchus), a member of the cartilaginous fish family Lamnidae, a family known
      for their morphological adaptations for high-performance locomotion and their
      similarity in hydromechanical design to tunas. Patterns of red muscle (RM) strain
      (i.e. relative length change) and activation were quantified at two axial
      positions ( approximately 0.4 and 0.6L, where L is total body length), using
      sonomicrometry and electromyography (EMG), and correlated with simultaneous
      measurements of dorsal midline kinematics during steady swimming ( approximately
      0.5-1 L s(-1)). RM strain varied longitudinally with strain amplitudes ranging
      from 5.5+/-1.1% (s.e.m.) in the anterior to 8.7+/-0.9% in the posterior. We found
      no significant longitudinal variation in patterns of RM activation, with mean
      onset of activation occurring at 83-84 degrees (90 degrees is peak length) and
      offset at 200-210 degrees at both body positions. Likewise, duty cycles were
      similar: 35.5+/-1.0% in the anterior and 32.2+/-1.6% in the posterior. Comparison
      of the timing of waves of dorsal midline curvature and predicted strain relative
      to measured RM strain revealed a phase shift between RM shortening and local body
      bending. Furthermore, when the body is bent passively, RM shortens synchronously
      with the surrounding white muscle (WM) and skin, as expected. During active
      swimming, peaks in RM strain were delayed relative to peaks in WM strain by a
      mean of approximately 10% of the tailbeat cycle, with one individual as high as
      approximately 17% in the anterior and nearly 50% in the posterior. The
      longitudinal consistency in the EMG/strain phase relationship in the mako is
      similar to that in the leopard shark, suggesting a consistent trend among sharks
      using different locomotor modes. However, unlike in the leopard shark, RM
      shortening in the mako is physically uncoupled from deformation of the
      surrounding body during steady swimming, a characteristic shared between the mako
      and tunas.

PMID- 15939776
TI  - Adaptations to an extreme environment: retinal organisation and spectral
      properties of photoreceptors in Antarctic notothenioid fish.
AB  - The Notothenioid suborder of teleosts comprises a number of species that live
      below the sea ice of the Antarctic. The presence of 'antifreeze' glycoproteins in
      these fish as an adaptation to freezing temperature has been well documented but
      little is known about the adaptations of the visual system of these fish to a
      light environment in which both the quantity and spectral composition of
      downwelling sunlight has been reduced by passage through ice and snow. In this
      study, we show that the red/long-wave sensitive (LWS) opsin gene is not present
      in these fish but a UV-sensitive short-wave sensitive (SWS1) pigment is expressed
      along with blue-sensitive (SWS2) and green/middle-wave sensitive (Rh2) pigments.
      The identity and spectral location of maximal absorbance of the SWS1 and Rh2
      pigments was confirmed by in vitro expression of the recombinant opsins followed
      by regeneration with 11-cis retinal. Only the SWS2 pigment showed interspecific
      variations in peak absorbance. Expression of the Rh2 opsin is localised to double
      cone receptors in both the central and peripheral retina, whereas SWS2 opsin
      expression is present only in the peripheral retina. SWS1 cones could not be
      identified by either microspectrophotometry or in situ hybridisation, presumably
      reflecting their low number and/or uneven distribution across the retina. A study
      of photoreceptor organisation in the retina of two species, the shallower
      dwelling Trematomus hansoni and the deeper dwelling Dissostichus mawsoni,
      identified a square mosaic in the former, and a row mosaic in the latter species;
      the row mosaic in Dissostichus mawsoni with less tightly packed cone
      photoreceptors allows for a higher rod photoreceptor density.

PMID- 15939778
TI  - Determination of the exact copy numbers of particular mRNAs in a single cell by
      quantitative real-time RT-PCR.
AB  - Gene expression is differently regulated in every cell even though the cells are
      included in the same tissue. For this reason, we need to measure the amount of
      mRNAs in a single cell to understand transcription mechanism better. However,
      there are no accurate, rapid and appropriate methods to determine the exact copy
      numbers of particular mRNAs in a single cell. We therefore developed a procedure
      for isolating a single, identifiable cell and determining the exact copy numbers
      of mRNAs within it. We first isolated the cerebral giant cell of the pond snail
      Lymnaea stagnalis as this neuron plays a key role in the process of memory
      consolidation of a learned behavior brought about by associative learning of
      feeding behavior. We then determined the copy numbers of mRNAs for the cyclic AMP
      responsive element binding proteins (CREBs). These transcription factors play an
      important role in memory formation across animal species. The protocol uses two
      techniques in concert with each other: a technique for isolating a single neuron
      with newly developed micromanipulators coupled to an assay of mRNAs by
      quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR).
      The molecular assay determined the mRNA copy numbers, each of which was compared
      with a standard curve prepared from cDNA solutions corresponding to the serially
      diluted solutions of Lymnaea CREB mRNA. The standard curves were linear within a
      range of 10 to 10(5) copies, and the intra-assay variation was within 15%. Each
      neuron removed from the ganglia was punctured to extract the total RNA directly
      and was used for the assay without further purification. Using this two-step
      procedure, we found that the mRNA copy number of CREB repressor (CREB2) was 30
      240 in a single cerebral giant cell, whereas that of CREB activator (CREB1) was
      below the detection limits of the assay (< 25). These results suggest that the
      CREB cascade is regulated by an excess amount of CREB2 in the cerebral giant
      cells. Our procedure is the only quantitative analysis for elucidation of the
      dynamics of gene transcription in a single cell.

PMID- 15939779
TI  - Do monarch butterflies use polarized skylight for migratory orientation?
AB  - To test if migratory monarch butterflies use polarized light patterns as part of
      their time-compensated sun compass, we recorded their virtual flight paths in a
      flight simulator while the butterflies were exposed to patches of naturally
      polarized blue sky, artificial polarizers or a sunny sky. In addition, we tested
      butterflies with and without the polarized light detectors of their compound eye
      being occluded. The monarchs' orientation responses suggested that the
      butterflies did not use the polarized light patterns as a compass cue, nor did
      they exhibit a specific alignment response towards the axis of polarized light.
      When given direct view of the sun, migratory monarchs with their polarized light
      detectors painted out were still able to use their time-compensated compass: non
      clockshifted butterflies, with their dorsal rim area occluded, oriented in their
      typical south-southwesterly migratory direction. Furthermore, they shifted their
      flight course clockwise by the predicted approximately 90 degrees after being
      advance clockshifted 6 h. We conclude that in migratory monarch butterflies,
      polarized light cues are not necessary for a time-compensated celestial compass
      to work and that the azimuthal position of the sun disc and/or the associated
      light-intensity and spectral gradients seem to be the migrants' major compass
      cue.

PMID- 15939780
TI  - Temperature-dependent protein synthesis capacities in Antarctic and temperate
      (North Sea) fish (Zoarcidae).
AB  - For an evaluation of effects of seasonal cold acclimation and evolutionary cold
      adaptation on protein synthesis capacity, the protein synthesis apparatus was
      isolated from the gills and white muscle of Antarctic eelpout Pachycara
      brachycephalum and North Sea eelpout Zoarces viviparus. Both species had been
      acclimated to 0 degrees C (control) and 5 degrees C (Antarctic) and 5 degrees C
      and 10 degrees C (North Sea control). The translational capacities of the protein
      synthesis machineries were determined in an optimised cell-free in vitro system.
      The results demonstrate that tissues from the polar zoarcid possess cold-adapted
      protein synthesis machineries, indicated by low activation energies and,
      especially, high RNA translational capacities at similar RNA:protein ratios when
      compared to temperate zoarcids at 10 degrees C. When both species were brought to
      5 degrees C, the temperate species displayed cold compensated protein synthesis
      capacities caused by elevated RNA:protein ratios. Warm exposure (from 0 to 5
      degrees C) of the Antarctic zoarcid revealed a capacity for thermal acclimation
      indicated by a reduction in protein synthesis capacities associated with lower
      RNA:protein ratios.

PMID- 15939781
TI  - Nitric oxide and the control of catecholamine secretion in rainbow trout
      Oncorhynchus mykiss.
AB  - An in situ saline-perfused posterior cardinal vein preparation was used to assess
      the role of nitric oxide (NO) in the regulation of basal and stimulus-evoked
      catecholamine secretion from rainbow trout Oncorhynchus mykiss chromaffin cells.
      Addition of the NO donor, sodium nitroprusside (SNP) to the inflowing perfusate
      abolished catecholamine secretion during electrical field stimulation, thereby
      establishing the potential for NO to act as a potent inhibitor of catecholamine
      release. A possible role for endogenously produced NO was established by
      demonstrating that stimulus-evoked (depolarizing levels of KCl or electrical
      field stimulation) catecholamine secretion was markedly stimulated in the
      presence of the nitric oxide synthase (NOS) inhibitors l-NAME and 7-NI. Although
      in vitro experiments demonstrated that catecholamine degradation was enhanced by
      NO in a dose-dependent manner, the dominant factor contributing to the reduction
      in catecholamine appearance in the perfusate was specific inhibition of
      catecholamine secretion. Subsequent experiments were performed to identify the
      NOS isoform(s) contributing to the inhibition of stimulus-evoked catecholamine
      secretion. Inducible NOS (iNOS; an enzyme that can be activated in the absence of
      Ca2+), although present in the vicinity of the chromaffin cells (based on mRNA
      measurements), does not appear to play a role because stimulus-evoked NO
      production was eliminated during perfusion with Ca2+-free saline. The potential
      involvement of endothelial NOS (eNOS) was revealed by showing that hypoxic
      perfusate evoked NO production and corresponded with an inhibition of stimulus
      evoked catecholamine secretion; chemical removal of the endothelium (using
      saponin) prevented the production of NO during hypoxia. However, because removal
      of the endothelium did not affect NO production during electrical field
      stimulation, it would appear that the neuronal form of NOS (nNOS) is the key
      isoform modulating catecholamine secretion from trout chromaffin cells.

PMID- 15939782
TI  - The anhydrobiotic potential and molecular phylogenetics of species and strains of
      Panagrolaimus (Nematoda, Panagrolaimidae).
AB  - Members of the genus Panagrolaimus are bacterial-feeding nematodes that occupy a
      diversity of niches ranging from Antarctic and temperate soils to terrestrial
      mosses. Some members of this genus are able to survive extreme desiccation by
      entering into a state of suspended animation known as anhydrobiosis. We have
      assembled a collection of Panagrolaimus species and strains and have investigated
      their anhydrobiotic phenotypes. Our data show that within the genus Panagrolaimus
      there is a continuum of strains ranging from those unable to survive exposure to
      low relative humidity (RH) without prior preconditioning at high RH (slow
      desiccation strategists), through strains that have limited ability to survive
      rapid desiccation but whose anhydrobiotic ability improves upon preconditioning,
      to strains such as P. superbus that can readily survive immediate exposure to
      severe desiccation (fast desiccation strategists). Using this panel of nematodes
      we investigated the effect of preincubation at high RH on the accumulation of
      trehalose and on the nematodes' anhydrobiotic potential. We found that there is a
      strong correlation between trehalose induction and anhydrobiotic survival in
      Panagrolaimus. Furthermore, the high trehalose levels observed in fully hydrated
      P. superbus (10% dry mass) suggest that constitutive expression of trehalose pre
      adapts this fast dehydration strategist to combat desiccation. All the strains
      observed, regardless of survival rates, undertook both coiling and clumping,
      which has the effect of reducing surface area and slowing the rate of water loss
      during desiccation. Phylogenetic analyses were carried out to investigate whether
      the observed anhydrobiotic phenotypes were the result of convergent evolution or
      represented a single phylogenetic lineage. These analyses, derived from
      alignments of the rDNA ITS and D3 sequences, indicate that the strongly
      anhydrobiotic strains of Panagrolaimus form a single phylogenetic lineage, which
      is separate from the weakly anhydrobiotic strains. The weakly anhydrobiotic
      strains are also phylogenetically divergent from each other. Our data indicate
      that Panagrolaimus has the potential to be an excellent model system for the
      investigation of molecular aspects of nematode anhydrobiosis.

PMID- 15939783
TI  - Maximal metabolic rates during voluntary exercise, forced exercise, and cold
      exposure in house mice selectively bred for high wheel-running.
AB  - Selective breeding for high wheel-running activity has generated four lines of
      laboratory house mice (S lines) that run about 170% more than their control
      counterparts (C lines) on a daily basis, mostly because they run faster. We
      tested whether maximum aerobic metabolic rates (V(O2max)) have evolved in concert
      with wheel-running, using 48 females from generation 35. Voluntary activity and
      metabolic rates were measured on days 5+6 of wheel access (mimicking conditions
      during selection), using wheels enclosed in metabolic chambers. Following this,
      V(O2max) was measured twice on a motorized treadmill and twice during cold
      exposure in a heliox atmosphere (HeO2). Almost all measurements, except heliox
      V(O2max), were significantly repeatable. After accounting for differences in body
      mass (S < C) and variation in age at testing, S and C did not differ in V(O2max)
      during forced exercise or in heliox, nor in maximal running speeds on the
      treadmill. However, running speeds and V(O2max) during voluntary exercise were
      significantly higher in S lines. Nevertheless, S mice never voluntarily achieved
      the V(O2max) elicited during their forced treadmill trials, suggesting that
      aerobic capacity per se is not limiting the evolution of even higher wheel
      running speeds in these lines. Our results support the hypothesis that S mice
      have genetically higher motivation for wheel-running and they demonstrate that
      behavior can sometimes evolve independently of performance capacities. We also
      discuss the possible importance of domestication as a confounding factor to
      extrapolate results from this animal model to natural populations.

PMID- 15939784
TI  - Acoustic characteristics of underwater tail slaps used by Norwegian and Icelandic
      killer whales (Orcinus orca) to debilitate herring (Clupea harengus).
AB  - Norwegian killer whales debilitate prey by slapping their tails into herring
      schools. These underwater tail slaps produce a thud-like sound. It is unclear
      whether this sound is caused by cavitation and/or physical contact between
      herring and whale tail. Also the forces causing debilitation of the fish are not
      understood. Here we present an acoustic analysis of underwater tail slaps using a
      multi-channel wide (150 kHz) band recording system. Underwater tail slaps
      produced by Norwegian killer whales generated sounds consisting of multiple
      pulses with source levels of 186+/-5.4 dB (pp) re.1 microPa at 1 m (+/-1 s.d., N
      = 4). The -3 dB and 97% energy bandwidths were 36.8+/-22.5 kHz and 130.5+/-17.5
      kHz (+/-1 s.d., N = 13), respectively, with a centre frequency of 46.1+/-22.3
      kHz. The similarities between the acoustic properties of underwater tail slaps
      recorded from killer whales in Norway, and thud-like sounds recorded from killer
      whales in Iceland suggest that Norwegian and Icelandic killer whales use similar
      hunting techniques. The acoustic characteristics of sounds produced by underwater
      tail slaps were similar to the ones from other cavitation sound sources described
      in the literature, both in term of temporal and frequency features as well as in
      source level. We suggest that multiple factors generated by the tail slaps like
      particle fluctuations, turbulence, pressure changes and physical impact cause
      debilitation of herring.

PMID- 15939785
TI  - Mycobacterium tuberculosis and the host response.
AB  - Mycobacterium tuberculosis remains a leading cause of morbidity and mortality
      worldwide. Advances reported at a recent international meeting highlight insights
      and controversies in the genetics of M. tuberculosis and the infected host, the
      nature of protective immune responses, adaptation of the bacillus to host-imposed
      stresses, animal models, and new techniques.

PMID- 15939786
TI  - The career of Maclyn McCarty.
AB  - On January 2, 2005, the scientific community lost a valued colleague and friend.
      Maclyn McCarty, or "Mac," as he was better known, was perhaps most recognized for
      his part in the discovery of DNA as the carrier of genetic information. But
      McCarty's scientific career was long and fruitful, and his contributions to
      science were vast. This retrospective offers a look at some of Mac's other
      notable scientific achievements.

PMID- 15939787
TI  - Mutational escape from CD8+ T cell immunity: HCV evolution, from chimpanzees to
      man.
AB  - The mechanisms by which the hepatitis C virus (HCV) establishes persistence are
      not yet fully understood. Previous chimpanzee and now human studies suggest that
      mutations within MHC class I-restricted HCV epitopes might contribute to viral
      escape from cytotoxic T lymphocyte (CTL) responses. However, there are several
      outstanding questions regarding the role of escape mutations in viral persistence
      and their fate in the absence of immune selection pressure.

PMID- 15939788
TI  - Immune evasion versus recovery after acute hepatitis C virus infection from a
      shared source.
AB  - Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the
      determinants of spontaneous resolution versus chronicity remain incompletely
      understood. In particular, because of the retrospective nature and unknown source
      of infection in most human studies, direct evidence for emergence of escape
      mutations in immunodominant major histocompatibility complex class I-restricted
      epitopes leading to immune evasion is extremely limited. In two patients infected
      accidentally with an identical HCV strain but who developed divergent outcomes,
      the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T
      cells that targeted a single epitope in one patient was associated with
      mutational escape and viral persistence. Statistical evidence for positive
      Darwinian selective pressure against an immunodominant epitope is presented. Wild
      type cytotoxic T lymphocytes persisted even after the cognate antigen was no
      longer present.

PMID- 15939789
TI  - An essential role for SKAP-55 in LFA-1 clustering on T cells that cannot be
      substituted by SKAP-55R.
AB  - Lymphocyte function-associated antigen (LFA)-1 clustering, which is needed for
      high avidity binding to intercellular adhesion molecule (ICAM)-1 and -2,
      regulates T cell motility and T cell-antigen-presenting cell (APC) conjugation.
      In this study, down-regulation of SKAP-55 by small interfering RNAs (siRNAs)
      identified an essential role for this adaptor molecule in the T cell receptor
      (TCR)-mediated "inside-out signaling" that is needed for LFA-1 clustering and T
      cell-APC conjugation. In contrast, down-regulation of SKAP-55 had no effect on
      TCR-CD3 clustering. Furthermore, the expression of the related protein SKAP-55R
      failed to compensate for the loss of SKAP-55 in LFA-1 clustering, indicating that
      SKAP-55 has a unique function that cannot be replaced by this closely related
      protein. Our findings therefore indicate that SKAP-55, unlike SKAP-55R, is
      specifically tailored as an essential component of the inside-out signaling
      events that couple the TCR to LFA-1 clustering and T cell-APC conjugation.

PMID- 15939790
TI  - Cellular immune selection with hepatitis C virus persistence in humans.
AB  - Hepatitis C virus (HCV) infection frequently persists despite substantial virus
      specific cellular immune responses. To determine if immunologically driven
      sequence variation occurs with HCV persistence, we coordinately analyzed sequence
      evolution and CD8+ T cell responses to epitopes covering the entire HCV
      polyprotein in subjects who were followed prospectively from before infection to
      beyond the first year. There were no substitutions in T cell epitopes for a year
      after infection in a subject who cleared viremia. In contrast, in subjects with
      persistent viremia and detectable T cell responses, we observed substitutions in
      69% of T cell epitopes, and every subject had a substitution in at least one
      epitope. In addition, amino acid substitutions occurred 13-fold more often within
      than outside T cell epitopes (P < 0.001, range 5-38). T lymphocyte recognition of
      8 of 10 mutant peptides was markedly reduced compared with the initial sequence,
      indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of
      known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These
      findings reveal two distinct mechanisms of sequence evolution involved in HCV
      persistence: viral escape from CD8+ T cell responses and optimization of
      replicative capacity.

PMID- 15939791
TI  - Divergent and convergent evolution after a common-source outbreak of hepatitis C
      virus.
AB  - The genomic sequences of viruses that are highly mutable and cause chronic
      infection tend to diverge over time. We report that these changes represent both
      immune-driven selection and, in the absence of immune pressure, reversion toward
      an ancestral consensus. Sequence changes in hepatitis C virus (HCV) structural
      and nonstructural genes were studied in a cohort of women accidentally infected
      with HCV in a rare common-source outbreak. We compared sequences present in serum
      obtained 18-22 yr after infection to sequences present in the shared inoculum and
      found that HCV evolved along a distinct path in each woman. Amino acid
      substitutions in known epitopes were directed away from consensus in persons
      having the HLA allele associated with that epitope (immune selection), and toward
      consensus in those lacking the allele (reversion). These data suggest that
      vaccines for genetically diverse viruses may be more effective if they represent
      consensus sequence, rather than a human isolate.

PMID- 15939792
TI  - Inflammation and the reciprocal production of granulocytes and lymphocytes in
      bone marrow.
AB  - The coordinated production of leukocytes in bone marrow is crucial for innate and
      adaptive immunity. Inflammation alters normal leukocyte production by promoting
      granulopoiesis over lymphopoiesis, a response that supports the reactive
      neutrophilia that follows infection. Here we demonstrate that this specialization
      for granulopoiesis is determined by inflammation-induced reductions of growth and
      retention factors, most significantly stem cell factor and CXCL12, which act
      preferentially to inhibit lymphoid development. These hierarchical effects
      suggest that the normal equilibrium of leukocyte production in bone marrow is
      determined by lymphopoiesis' higher demand for specific growth factors and/or
      retention signals. Inflammation regulates this balance by reducing growth factors
      that have less impact on developing neutrophils than lymphocytes. We demonstrate
      that granulopoiesis and lymphopoiesis are coupled specifically in the bone marrow
      by development in a common niche and propose that the leukopoietic equilibrium is
      specified by limiting amounts of developmental resources.

PMID- 15939793
TI  - Coexpression of CD25 and CD27 identifies FoxP3+ regulatory T cells in inflamed
      synovia.
AB  - A better understanding of the role of CD4+CD25+ regulatory T cells in disease
      pathogenesis should follow from the discovery of reliable markers capable of
      discriminating regulatory from activated T cells. We report that the CD4+CD25+
      population in synovial fluid of juvenile idiopathic arthritis (JIA) patients
      comprises both regulatory and effector T cells that can be distinguished by
      expression of CD27. CD4+CD25+CD27+ cells expressed high amounts of FoxP3 (43% of
      them being FoxP3+), did not produce interleukin (IL)-2, interferon-gamma, or
      tumor necrosis factor, and suppressed T cell proliferation in vitro, being, on a
      per cell basis, fourfold more potent than the corresponding peripheral blood
      population. In contrast, CD4+CD25+CD27- cells expressed low amounts of FoxP3,
      produced effector cytokines and did not suppress T cell proliferation. After in
      vitro activation and expansion, regulatory but not conventional T cells
      maintained high expression of CD27. IL-7 and IL-15 were found to be present in
      synovial fluid of JIA patients and, when added in vitro, abrogated the
      suppressive activity of regulatory T cells. Together, these results demonstrate
      that, when used in conjunction with CD25, CD27 is a useful marker to distinguish
      regulatory from effector T cells in inflamed tissues and suggest that at these
      sites IL-7 and IL-15 may interfere with regulatory T cell function.

PMID- 15939794
TI  - Live imaging of effector cell trafficking and autoantigen recognition within the
      unfolding autoimmune encephalomyelitis lesion.
AB  - We tracked pathogenic myelin basic protein-specific CD4+ effector T cells in
      early central nervous system (CNS) lesions of experimental autoimmune
      encephalomyelitis (EAE) by combining two-photon imaging and fluorescence video
      microscopy. We made two key observations: (a) the majority of the cells (65%)
      moved fast (maximal speed 25 microm/min) and apparently nondirected through the
      compact tissue; and (b) a second group of effector T cells (35%) appeared
      tethered to a fixed point. Polarization of T cell receptor and adhesion molecules
      (lymphocyte function-associated antigen 1) towards this fixed point suggests the
      formation of immune synapses. Nonpathogenic, ovalbumin-specific T cells were not
      tethered in the CNS and did not form synapse-like contacts, but moved through the
      tissue. After intrathecal injection of antigen, 40% of ovalbumin-specific T cells
      became tethered. Conversely, injection of anti-major histocompatibility complex
      class II antibodies profoundly reduced the number of stationary pathogenic T
      cells within the CNS (to 15%). We propose that rapid penetration of the CNS
      parenchyma by numerous autoimmune effector T cells along with multiple
      autoantigen-presentation events are responsible for the fulminate development of
      clinical EAE.

PMID- 15939795
TI  - Mimicry of a constitutively active pre-B cell receptor in acute lymphoblastic
      leukemia cells.
AB  - Pre-B cells undergo apoptosis unless they are rescued by pre-B cell receptor
      dependent survival signals. We previously showed that the BCR-ABL1 kinase that is
      expressed in pre-B lymphoblastic leukemia bypasses selection for pre-B cell
      receptor-dependent survival signals. Investigating possible interference of BCR
      ABL1 with pre-B cell receptor signaling, we found that neither SYK nor SLP65 can
      be phosphorylated in response to pre-B cell receptor engagement. Instead,
      Bruton's tyrosine kinase (BTK) is constitutively phosphorylated by BCR-ABL1.
      Activated BTK is essential for survival signals that otherwise would arise from
      the pre-B cell receptor, including activation of PLCgamma1, autonomous Ca2+
      signaling, STAT5-phosphorylation, and up-regulation of BCLX(L). Inhibition of BTK
      activity specifically induces apoptosis in BCR-ABL1+ leukemia cells to a similar
      extent as inhibition of BCR-ABL1 kinase activity itself. However, BCR-ABL1 cannot
      directly bind to full-length BTK. Instead, BCR-ABL1 induces the expression of a
      truncated splice variant of BTK that acts as a linker between the two kinases. As
      opposed to full-length BTK, truncated BTK lacks kinase activity yet can bind to
      BCR-ABL1 through its SRC-homology domain 3. Acting as a linker, truncated BTK
      enables BCR-ABL1-dependent activation of full-length BTK, which initiates
      downstream survival signals and mimics a constitutively active pre-B cell
      receptor.

PMID- 15939797
TI  - Norepinephrine induces lipolysis in beta1/beta2/beta3-adrenoceptor knockout mice.
AB  - Catecholamines are major stimulants of adipose tissue metabolism. Norepinephrine
      and epinephrine act through three subtypes of beta-adrenoceptors (beta-AR)
      expressed in the adipocytes. The aim of this work was to study the mechanisms of
      lipid mobilization in beta1/beta2/beta3-AR triple-knockout (beta-less) mice.
      Glycerol and nonesterified fatty acids released from isolated adipocytes were
      measured as an index of lipolytic activity. There was no difference between the
      two genotypes for basal lipolysis and lipolytic response to corticotropin or to
      agents acting at the adenylyl cyclase and protein kinase A levels. The lipolytic
      response to norepinephrine and beta-AR agonists was blunted in beta-less mice.
      However, a residual low-affinity lipolytic effect was observed in the presence of
      catecholamines and beta3-AR agonists but not of beta1- or beta2-AR agonists. cAMP
      levels were increased by a beta-AR agonist in white and brown adipocytes of beta
      less mice. The residual lipolytic effect was blocked by beta-AR antagonists. It
      was mediated neither by alpha1- or alpha2-AR nor dopaminergic, serotonergic, and
      histaminergic by receptors. Bioinformatic analyses do not provide evidence for a
      fourth beta-AR. We conclude that the residual lipolytic effect observed in beta
      less mice can be attributed to an unknown Gs-protein-coupled receptor with low
      affinity for catecholamines.

PMID- 15939796
TI  - SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and
      infected erythrocytes.
AB  - The surfaces of the infected erythrocyte (IE) and the merozoite, two
      developmental stages of malaria parasites, expose antigenic determinants to the
      host immune system. We report on surface-associated interspersed genes (surf
      genes), which encode a novel polymorphic protein family, SURFINs, present on both
      IEs and merozoites. A SURFIN expressed in 3D7 parasites, SURFIN4.2, was
      identified by mass spectrometric analysis of peptides cleaved off the surface of
      live IEs with trypsin. SURFINs are encoded by a family of 10 surf genes,
      including three predicted pseudogenes, located within or close to the
      subtelomeres of five of the chromosomes. SURFINs show structural and sequence
      similarities with exported surface-exposed proteins (PvSTP1, PkSICAvar, PvVIR,
      Pf332, and PfEMP1) of several Plasmodium species. SURFIN4.2 of a parasite other
      than 3D7 (FCR3S1.2) showed polymorphisms in the extracellular domain, suggesting
      sequence variability between genotypes. SURFIN4.2 not only was found
      cotransported with PfEMP1 and RIFIN to the IE surface, but also accumulated in
      the parasitophorous vacuole. In released merozoites, SURFIN4.2 was present in an
      amorphous cap at the parasite apex, where it may be involved in the invasion of
      erythrocytes. By exposing shared polymorphic antigens on IEs and merozoites, the
      parasite may coordinate the antigenic composition of these attachment surfaces
      during growth in the bloodstream.

PMID- 15939798
TI  - The reduced folate carrier gene is a novel selectable marker for recombinant
      protein overexpression.
AB  - Folate cofactors are one-carbon donors essential for the biosynthesis of purines
      and thymidylate. Mammalian cells are devoid of folate biosynthesis and are
      therefore folate auxotrophs that take up folate vitamins primarily via the
      reduced folate carrier (RFC). In this study, we showed that the human RFC (hRFC)
      gene can serve as a novel selectable marker for the overproduction of recombinant
      proteins. Toward this end, a hemagglutinin (HA) epitope tagged hRFC (hRFC-HA) was
      introduced into a bicistronic vector (pIRES2-EGFP), upstream of an enhanced green
      fluorescent protein (EGFP) reporter gene. Chinese hamster ovary cells deficient
      in RFC activity were isolated and transfected with this construct, followed by
      gradual deprivation of leucovorin, the sole folate source in the growth medium.
      Only cells with hRFC-HA overexpression were able to take up leucovorin and
      thereby survive these selective conditions. Western blot and immunofluorescence
      analyses confirmed that the hRFC-HA was overexpressed at extremely high levels,
      properly glycosylated and sorted out to the plasma membrane. This resulted in a
      approximately 450-fold increase in [3H]methotrexate influx and approximately 100
      fold increased sensitivity to methotrexate, relative to untransfected RFC
      deficient cells. Flow cytometric analysis consistently revealed that EGFP was
      overexpressed approximately 100-fold above the autofluorescence level.
      Overproduction of hRFC-HA and EGFP was stably maintained for at least 2 months in
      a constant concentration of leucovorin. These results establish a novel RFC-based
      metabolic selection system for the efficient overexpression of recombinant
      proteins. Furthermore, the possible implications to subcellular transporter
      localization and restoration of MTX sensitivity in drug-resistant tumors by RFC
      based gene therapy are discussed.

PMID- 15939799
TI  - Vitamin K3 (menadione)-induced oncosis associated with keratin 8 phosphorylation
      and histone H3 arylation.
AB  - The vitamin K analog menadione (K3), capable of both redox cycling and arylating
      nucleophilic substrates by Michael addition, has been extensively studied as a
      model stress-inducing quinone in both cell culture and animal model systems.
      Exposure of keratin 8 (k-8) expressing human breast cancer cells (MCF7, T47D,
      SKBr3) to K3 (50-100 microM) induced rapid, sustained, and site-specific k-8
      serine phosphorylation (pSer73) dependent on signaling by a single mitogen
      activated protein kinase (MAPK) pathway, MEK1/2. Normal nuclear morphology and k
      8 immunofluorescence coupled with the lack of DNA laddering or other features of
      apoptosis indicated that K3-induced cytotoxicity, evident within 4 h of treatment
      and delayed but not prevented by MEK1/2 inhibition, was due to a form of stress
      activated cell death known as oncosis. Independent of MAPK signaling was the
      progressive appearance of K3-induced cellular fluorescence, principally nuclear
      in origin and suggested by in vitro fluorimetry to have been caused by K3 thiol
      arylation. Imaging by UV transillumination of protein gels containing nuclear
      extracts from K3-treated cells revealed a prominent 17-kDa band shown to be
      histone H3 by immunoblotting and mass spectrometry (MS). K3 arylation of histones
      in vitro followed by electrospray ionization-tandem MS analyses identified the
      unique Cys110 residue within H3, exposed only in the open chromatin of
      transcriptionally active genes, as a K3 arylation target. These findings
      delineate new pathways associated with K3-induced stress and suggest a
      potentially novel role for H3 Cys110 as a nuclear stress sensor.

PMID- 15939800
TI  - Identification of four novel exon 5 splice variants of the mouse mu-opioid
      receptor gene: functional consequences of C-terminal splicing.
AB  - The rat mu-opioid receptor clone in which novel exon 5 was found in the place of
      exon 4 (MOR-1B) was one of the first MOR-1 variants described. We now have
      identified the mouse homolog of the rat MOR-1B as well as four additional
      variants derived from splicing from exon 3 into different sites within exon 5.
      The sequences of all of the variants were identical except for the intracellular
      tip of the C terminus encoded by exon 5, where each variant predicted a unique
      amino acid sequence ranging from 2 to 39 amino acids. All of the mMOR-1B variants
      were selective for mu-opioids in receptor-binding assays, as anticipated, because
      they all have identical binding pockets defined by the transmembrane domains.
      However, the relative potency and efficacy of mu-agonists to each other varied
      from variant to variant in guanosine 5'-O-(3-[35S]thio)triphosphate-binding
      studies, as shown by morphine-6beta-glucuronide, which was the most efficacious
      agent against mouse MOR-1B1 (mMOR-1B1) and the least efficacious agent against
      mMOR-1B2. mMOR-1B4 was quite unusual. Although mMOR-1B4 was mu-selective in
      receptor-binding studies and antagonists labeled mMOR-1B4 well, the binding
      affinities of most of the mu-agonists were far lower than those seen with mMOR-1,
      suggesting that the 39 amino acids at the C terminus of mMOR-1B4 influences the
      conformation of the receptor and its ligand recognition site itself either
      directly or through its interactions with other proteins. In conclusion,
      alterations in the amino acid sequence of the C terminus do not alter the mu
      specificity of the receptor but they can influence the binding characteristics,
      efficacy, and potency of mu-opioids.

PMID- 15939801
TI  - Novel plant substances acting as beta subunit isoform-selective positive
      allosteric modulators of GABAA receptors.
AB  - GABAA receptors are modulated by a large variety of compounds. A common chemical
      characteristic of most of these modulators is that they contain a cyclic entity.
      Three linear molecules of a polyacetylene structure were isolated from the East
      African medicinal plant Cussonia zimmermannii Harms and shown to allosterically
      stimulate GABAA receptors. Stimulation was not abolished by the absence of the
      gamma2 subunit, the benzodiazepine antagonist Ro15-1788 (8-fluoro-5,6-dihydro-5
      methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid ethyl ester),
      or the point mutation beta2N265S that abolishes effects by loreclezole. At a
      concentration of 30 microM, the substances by themselves elicited only tiny
      currents. Maximal stimulation at alpha1beta2gamma2 amounted to 110 to 450% for
      the three substances, and half-maximal stimulation was observed at concentrations
      of 1 to 2 muM. Stimulation was subunit composition-dependent and was for the
      substance MS-1, alpha1beta2gamma2 approximately alpha1beta2 approximately
      alpha3beta2gamma2 > alpha2beta2gamma2 > alpha5beta2gamma2 approximately
      alpha1beta3gamma2 approximately alpha6beta2gamma2 > alpha1beta1gamma2, for MS-2
      alpha1beta2gamma2 approximately alpha3beta2gamma2 approximately alpha1beta2 >
      alpha2beta2gamma2 approximately alpha6beta2gamma2 approximately alpha5beta2gamma2
      > alpha1beta1gamma2, and for MS-4, alpha1beta2gamma2 approximately alpha1beta2
      approximately alpha5beta2gamma2 approximately alpha3beta2gamma2 approximately
      alpha2beta2gamma2 > alpha6beta2gamma2 >> alpha1beta1gamma2. Maximal stimulation
      by MS-1 was 450% at alpha1beta2gamma2, 80% at alpha1beta1gamma2, and 150% at
      alpha1beta3gamma2. MS-1 was thus specific for receptors containing the beta2
      subunit. The reversal potential was unaffected by 10 microM MS-1, whereas
      apparent picrotoxin affinity for current inhibition was increased approximately 3
      fold. In summary, these positive allosteric modulators of GABAA receptors of
      plant origin have a novel unusual chemical structure and act at a site
      independent of that of benzodiazepines and loreclezole.

PMID- 15939802
TI  - Pharmacological telomerase inhibition can sensitize drug-resistant and drug
      sensitive cells to chemotherapeutic treatment.
AB  - Effective strategies to reverse or prevent chemotherapeutic resistance are
      required before cancer therapies can be curative. Telomerase is the
      ribonucleoprotein responsible for de novo synthesis and maintenance of telomeres,
      and its activity is predominantly observed in cancer cells. The telomerase enzyme
      has been successfully inhibited or inactivated to sensitize cells to cellular
      stresses; however, no studies have determined yet the effect of combining a
      pharmacological inhibitor of telomerase catalysis and traditional
      chemotherapeutics for the treatment of drug-sensitive or drug-resistant cancers.
      Here, we describe the effect of 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-benzoic
      acid (BIBR1532), a small-molecule inhibitor of telomerase catalytic activity, on
      drug-resistant leukemia and breast cancer cells and their parental counterparts
      when treated in combination with chemotherapeutics. We observed that BIBR1532
      treated cells show progressive telomere shortening, decreased proliferative
      capacity, and sensitization to chemotherapeutic treatment. These effects are
      telomere length-dependent, because cells insensitive to BIBR1532 or cells
      released from telomerase inhibition did not demonstrate changes in growth ability
      or drug sensitivity. Our novel observations suggest that pharmacological
      telomerase inhibition in combination therapy may be a valid strategy for the
      treatment of both drug-sensitive and drug-resistant cancers.

PMID- 15939803
TI  - Lys418Asn polymorphism of the alpha2-adrenoceptor gene relates to serum uric acid
      levels but not to insulin sensitivity.
AB  - Hyperuricemia is associated with cardiovascular risk. The present study examines
      the association between serum uric acid (UA) elevation and the alpha2-, beta2-,
      and beta3-adrenoceptor polymorphisms. In 219 nonobese, normotensive,
      normouricemic (serum UA <6.5 mg/dL at entry) men, serum UA, plasma norepinephrine
      (NE), the homeostasis model assessment of insulin resistance (HOMA-IR), body mass
      index, total body fat mass, the alpha2A(Lys418Asn)-, beta2(Arg16Gly, Gln27Glu)-,
      and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured annually over 5
      years. Hyperuricemia was defined as a serum UA level of > or =mean+1 SD of 5.0
      mg/dL in the participants. At entry, there were 36 subjects who had hyperuricemia
      and 183 who had normal UA levels. A significant UA elevation for 5 years was
      defined as an increase in > or =10% in UA levels. There were 82 subjects who had
      significant UA elevations. The subjects who had hyperuricemia at entry in
      addition to the subjects who had significant UA elevations over the 5-year period
      carried a significantly higher frequency of the Asn418 allele of Lys418Asn.
      Additionally, subjects carrying the Asn418 allele had higher UA and plasma NE and
      greater elevations in UA over the study period, but HOMA-IR was similar. Insulin
      resistance at entry and during the study was associated with Arg16Gly
      polymorphisms but not with Lys418Asn polymorphisms. In conclusion, the Asn418
      allele of Lys418Asn is associated with either established hyperuricemia or the
      progressive elevation of UA over time. This polymorphism was not associated with
      insulin resistance in nonobese, normotensive individuals. Although hyperuricemia
      is of known relevance to insulin resistance, it appears to have different genetic
      determinants from insulin resistance in terms of adrenoceptor polymorphisms.

PMID- 15939804
TI  - Effect of compensated renal dysfunction on approved heart failure markers: direct
      comparison of brain natriuretic peptide (BNP) and N-terminal pro-BNP.
AB  - Brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are markers of
      heart failure. Although renal dysfunction may increase plasma concentrations, the
      magnitude of this effect has not been assessed in a head-to-head comparison
      between the clinically approved tests. We assessed the effect of compensated
      renal dysfunction on BNP (Triage BNP; Biosite) and NT-proBNP (elecsys proBNP;
      Roche) in 469 randomly selected stable outpatients after myocardial infarction
      (MI; Monitoring Trends and Determinants in Cardiovascular Diseases [MONICA]
      register Augsburg) who were characterized with respect to renal function
      (glomerular filtration rate [GFR]; Cockroft method) and left ventricular (LV)
      ejection fraction (EF) and mass (2D echocardiography). BNP and NT-proBNP were
      elevated in MI patients with LV dysfunction (LVD; EF <35%) compared with MI
      patients with preserved EF ( >45%; BNP 139+/-27 pg/mL versus 75+/-6; NT-proBNP
      816+/-237 pg/mL versus 243+/-20; both P <0.03). Among all MI patients, the
      prevalence of renal dysfunction (GFR <85 mL/min) was 24%. BNP and NT-proBNP were
      significantly elevated in MI patients with renal dysfunction (BNP 132+/-17 pg/mL
      versus 68+/-4 without renal dysfunction; NT-proBNP 535+/-80 pg/mL versus 232+/
      19; both P <0.05), and both markers were correlated with GFR in univariate and
      multivariate analyses (all P <0.01). When binary cut-off values were stratified
      according to the absence or presence of renal dysfunction (BNP 75 pg/mL and 125
      pg/mL, respectively; NT-proBNP 100 pg/mL and 350 pg/mL, respectively), the
      predictive power of both markers for the detection of LVD increased
      substantially. BNP and NT-proBNP are almost similarly influenced by mild-to
      moderate renal dysfunction. Renal dysfunction is a potential cause of elevated
      marker concentrations in the absence of LVD, and cut-off concentrations should be
      stratified according to renal function.

PMID- 15939805
TI  - Superiority of ambulatory over clinic blood pressure measurement in predicting
      mortality: the Dublin outcome study.
AB  - The purpose of this study was to determine if ambulatory blood pressure
      measurement predicted total and cardiovascular mortality over and beyond clinic
      blood pressure measurement and other cardiovascular risk factors; 5292 untreated
      hypertensive patients referred to a single blood pressure clinic who had clinic
      and ambulatory blood pressure measurement at baseline were followed up in a
      prospective study of mortality outcome. Multiple Cox regression was used to model
      time to total and cause-specific mortality for ambulatory blood pressure
      measurement while adjusting for clinic blood pressure measurement and other risk
      factors at baseline. There were 646 deaths (of which 389 were cardiovascular)
      during a median follow-up period of 8.4 years. With adjustment for gender, age,
      risk indices, and clinic blood pressure, higher mean values of ambulatory blood
      pressure were independent predictors for cardiovascular mortality. The relative
      hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06
      to 1.18; P<0.001) for daytime and 1.21 (1.15 to 1.27; P<0.001) for nighttime
      systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic
      blood pressure were 1.02 (0.99 to 1.07; P=NS) for daytime and 1.09 (1.04 to 1.13;
      P<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime
      ambulatory blood pressure remained significant after adjustment for daytime
      ambulatory blood pressure. These results have 2 important clinical messages:
      ambulatory measurement of blood pressure is superior to clinic measurement in
      predicting cardiovascular mortality, and nighttime blood pressure is the most
      potent predictor of outcome.

PMID- 15939806
TI  - Left ventricular hypertrophy in blacks and whites: different genes or different
      exposure?

PMID- 15939807
TI  - Left ventricular hypertrophy is more prevalent in blacks than whites in the
      general population: the Dallas Heart Study.
AB  - Although recent studies have suggested that blacks compared with whites have an
      increased prevalence of left ventricular hypertrophy, it remains uncertain
      whether this is true despite adjustment for body composition (fat mass and fat
      free mass) and when assessed by cardiac MRI in the general population. The Dallas
      Heart Study is a population-based study of Dallas County in which 1335 black and
      858 white participants 30 to 67 years of age underwent detailed assessment
      including dual-energy x-ray absorptiometry scan to measure body composition and
      cardiac MRI. Left ventricular hypertrophy, whether defined by indexation to body
      surface area (P<0.001), fat-free mass (P=0.002), or height2.7 (P<0.001) was 2- to
      3-fold more common in black versus white women. Similar results were seen when
      comparing black and white men (P<0.001 when left ventricular hypertrophy was
      indexed to body surface area or height2.7 and P=0.05 when indexed to fat-free
      mass). Ethnic disparities in left ventricular mass persisted in multivariable
      models despite adjustment for fat mass, fat-free mass, systolic blood pressure,
      age, gender, and measures of socioeconomic status. We conclude that blacks
      compared with whites have increased left ventricular mass and a 2- to 3-fold
      higher prevalence of left ventricular hypertrophy in the general population, as
      assessed by cardiac MRI. The ethnic differences in left ventricular mass are
      independent of differences in body composition.

PMID- 15939808
TI  - Activation of 5-hydroxytryptamine 1A receptors suppresses the cardiovascular
      response evoked from the dorsomedial hypothalamic nucleus.
AB  - The dorsomedial hypothalamic nucleus is a key component of the central pathways
      subserving the cardiovascular response to psychological stress, which is believed
      to be an important risk factor for hypertension. Previous studies indicate that 5
      hydroxytryptamine 1A receptors can modulate the cardiovascular responses
      associated with stress. In this study, we determined in anesthetized rats the
      effects of systemic or intracisternal administration of 8-hydroxy-2-(di-n
      propylamino)tetralin, a selective agonist of 5-hydroxytryptamine 1A receptors,
      and then subsequent administration of the selective antagonist WAY-100635 on the
      cardiovascular response evoked by activation of the dorsomedial hypothalamic
      nucleus (by microinjection of bicuculline). The increase in mean arterial
      pressure, heart rate, and renal sympathetic nerve activity (RSNA) evoked by
      bicuculline injection into the dorsomedial hypothalamic nucleus was greatly
      reduced (by 80% to 90%) by administration of 8-hydroxy-2-(di-n
      propylamino)tetralin and then completely restored by subsequent administration of
      WAY-100635, whether administered systemically or intracisternally. In contrast,
      systemic administration of 8-hydroxy-2-(di-n-propylamino)tetralin had no
      significant effect on the baseline level or reflex changes in RSNA evoked by
      chemoreceptor or baroreceptor stimulation and resulted in only a modest reduction
      (12 mm Hg) in baseline mean arterial pressure. The results indicate that
      activation of 5-hydroxytryptamine 1A receptors in the brain stem causes a potent
      and selective suppression of the hypertensive and sympathoexcitatory response
      evoked by stimulation of the dorsomedial hypothalamic nucleus but has little
      effect on the tonic level or baroreceptor or chemoreceptor reflex control of
      RSNA.

PMID- 15939809
TI  - PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin.
AB  - The adipose-specific protein adiponectin has been recently discovered to improve
      insulin sensitivity. Angiotensin type-1 receptor (AT1R) blockers (ARBs) reduce
      the incidence of type 2 diabetes mellitus by mostly unknown molecular mechanisms.
      To identify new antidiabetic mechanisms of ARBs, we studied the regulation of
      adiponectin by angiotensin II (Ang II) and different ARBs in murine 3T3-L1
      adipocytes and obese Zucker rats. Adiponectin protein expression was markedly
      stimulated by Ang II (5 nmol/L), which was inhibited by blockade of the AT2R, and
      further enhanced by the ARB irbesartan. Irbesartan-mediated adiponectin
      upregulation started beyond the concentrations needed for AT1R blockade and was
      also present in the absence of Ang II, implicating an AT1R-independent mechanism
      of action. Recently, certain ARBs (irbesartan, telmisartan) were identified as
      ligands of the peroxisome proliferator-activated receptor (PPAR)gamma.
      Telmisartan also stimulated adiponectin protein expression, whereas the non
      PPARgamma-activating ARB eprosartan had no effect. Blockade of PPARgamma
      activation by the PPARgamma antagonist GW9662 markedly inhibited irbesartan
      induced adiponectin expression. Cognate mRNA levels of adiponectin were not
      affected by ARBs. Kinetic studies using the protein synthesis inhibitor
      cycloheximide showed that irbesartan prevented the cellular depletion of
      adiponectin protein. Finally, administration of irbesartan to obese Zucker rats
      improved insulin sensitivity and attenuated adiponectin serum depletion. The
      present study demonstrates that AT2R activation and certain ARBs induce
      adiponectin in adipocytes, which was associated with an improvement of parameters
      of insulin sensitivity in vivo. ARB-induced adiponectin stimulation is likely to
      be mediated via PPARgamma activation involving a post-transcriptional mechanism.

PMID- 15939810
TI  - Aldosterone synthase inhibitor ameliorates angiotensin II-induced organ damage.
AB  - BACKGROUND: Aldosterone and angiotensin (Ang) II both may cause organ damage.
      Circulating aldosterone is produced in the adrenals; however, local cardiac
      synthesis has been reported. Aldosterone concentrations depend on the activity of
      aldosterone synthase (CYP11B2). We tested the hypothesis that reducing
      aldosterone by inhibiting CYP11B2 or by adrenalectomy (ADX) may ameliorate organ
      damage. Furthermore, we investigated how much local cardiac aldosterone
      originates from the adrenal gland. METHODS AND RESULTS: We investigated the
      effect of the CYP11B2 inhibitor FAD286, losartan, and the consequences of ADX in
      transgenic rats overexpressing both the human renin and angiotensinogen genes
      (dTGR). dTGR-ADX received dexamethasone and 1% salt. Dexamethasone-treated dTGR
      salt served as a control group in the ADX protocol. Untreated dTGR developed
      hypertension and cardiac and renal damage and had a 40% mortality rate (5/13) at
      7 weeks. FAD286 reduced mortality to 10% (1/10) and ameliorated cardiac
      hypertrophy, albuminuria, cell infiltration, and matrix deposition in the heart
      and kidney. FAD286 had no effect on blood pressure at weeks 5 and 6 but slightly
      reduced blood pressure at week 7 (177+/-6 mm Hg in dTGR+FAD286 and 200+/-5 mm Hg
      in dTGR). Losartan normalized blood pressure during the entire study. Circulating
      and cardiac aldosterone levels were reduced in FAD286 or losartan-treated dTGR.
      ADX combined with dexamethasone and salt treatment decreased circulating and
      cardiac aldosterone to barely detectable levels. At week 7, ADX-dTGR
      dexamethasone-salt had a 22% mortality rate compared with 73% in dTGR
      dexamethasone-salt. Both groups were similarly hypertensive (190+/-9 and 187+/-4
      mm Hg). In contrast, cardiac hypertrophy index, albuminuria, cell infiltration,
      and matrix deposition were significantly reduced after ADX (P<0.05). CONCLUSIONS:
      Aldosterone plays a key role in the pathogenesis of Ang II-induced organ damage.
      Both FAD286 and ADX reduced circulating and cardiac aldosterone levels. The
      present results show that aldosterone produced in the adrenals is the main source
      of cardiac aldosterone.

PMID- 15939811
TI  - Elastic-vessel arteritis in interleukin-1 receptor antagonist-deficient mice
      involves effector Th1 cells and requires interleukin-1 receptor.
AB  - BACKGROUND: In mice that lack interleukin-1 receptor antagonist (IL-1ra),
      transmural inflammation of the elastic arteries develops at sites of turbulent
      flow. We described late histopathology previously. Here, we investigate the
      cellular events in nonlethal arteritis at the aortic root and compare them with
      Takayasu's arteritis and giant cell arteritis. METHODS AND RESULTS: IL-1ra
      deficient mice were inbred from the original stocks and from BALB/c backcrosses.
      Disease was ascertained histologically and immunohistologically postmortem at the
      aortic root. Onset appeared to be stochastic and was not detectably age
      dependent; in our local Sf3 strain, the half-time of onset was approximately 52
      days. Loss of the type I IL-1 receptor suppressed the arteritis. Microvascular
      activation, as determined by absence of strong E-selectin expression, was absent
      from preaffected vessels. In mildly affected cases, infiltration was adventitial.
      In severely affected animals, infiltrates appeared to be active in destroying
      elastin, but resynthesis of disorganized elastin occurred at closely adjacent
      sites. Infiltrates consisted predominantly of macrophages but were rich in CD4+
      interferon-gamma+ cells, which are likely to represent Th1 cells. Dendritic cells
      accumulated in lesional areas. CONCLUSIONS: The arteritic phenotype of IL-1ra
      deficiency is mediated by the interleukin-1 receptor and involves effector Th1
      cells. The destructive pattern and many of the cellular features of arteritis in
      IL-1ra-deficient mice resemble the human elastic-vessel arteritides, for which
      these mice may be a useful animal model.

PMID- 15939812
TI  - Admission glucose and mortality in elderly patients hospitalized with acute
      myocardial infarction: implications for patients with and without recognized
      diabetes.
AB  - BACKGROUND: The relationship between admission glucose levels and outcomes in
      older diabetic and nondiabetic patients with acute myocardial infarction is not
      well defined. METHODS AND RESULTS: We evaluated a national sample of elderly
      patients (n=141,680) hospitalized with acute myocardial infarction from 1994 to
      1996. Admission glucose was analyzed as a categorical (< or =110, >110 to 140,
      >140 to 170, >170 to 240, >240 mg/dL) and continuous variable for its association
      with mortality in patients with and without recognized diabetes. A substantial
      proportion of hyperglycemic patients (eg, 26% of those with glucose >240 mg/dL)
      did not have recognized diabetes. Fewer hyperglycemic patients without known
      diabetes received insulin during hospitalization than diabetics with similar
      glucose levels (eg, glucose >240 mg/dL, 22% versus 73%; P<0.001). Higher glucose
      levels were associated with greater risk of 30-day mortality in patients without
      known diabetes (for glucose range from < or =110 to >240 mg/dL, 10% to 39%)
      compared with diabetics (range, 16% to 24%; P for interaction <0.001). After
      multivariable adjustment, higher glucose levels continued to be associated with a
      graded increase in 30-day mortality in patients without known diabetes (referent,
      glucose < or =110 mg/dL; range from glucose >110 to 140 mg/dL: hazard ratio [HR],
      1.17; 95% CI, 1.11 to 1.24; to glucose >240 mg/dL: HR, 1.87; 95% CI, 1.75 to
      2.00). In contrast, among diabetic patients, greater mortality risk was observed
      only in those with glucose >240 mg/dL (HR, 1.32; 95% CI, 1.17 to 1.50 versus
      glucose < or =110 mg/dL; P for interaction <0.001). One-year mortality results
      were similar. CONCLUSIONS: Elevated glucose is common, rarely treated, and
      associated with increased mortality risk in elderly acute myocardial infarction
      patients, particularly those without recognized diabetes.

PMID- 15939813
TI  - Novel molecular mechanism involving alpha1D (Cav1.3) L-type calcium channel in
      autoimmune-associated sinus bradycardia.
AB  - BACKGROUND: Congenital heart block (CHB) is an autoimmune disease that affects
      fetuses/infants born to mothers with anti-Ro/La antibodies (positive IgG).
      Although the hallmark of CHB is complete atrioventricular block, sinus
      bradycardia has been reported recently in animal models of CHB. Interestingly,
      knockout of the neuroendocrine alpha1D Ca channel in mice results in significant
      sinus bradycardia and atrioventricular block, a phenotype reminiscent to that
      seen in CHB. Here, we tested the hypothesis that the alpha1D Ca channel is a
      novel target for positive IgG. METHODS AND RESULTS: Reverse transcription
      polymerase chain reaction, confocal indirect immunostaining, and Western blot
      data established the expression of the alpha1D Ca channel in the human fetal
      heart. The effect of positive IgG on alpha1D Ca current (I(Ca-L)) was
      characterized in heterologous expression systems (tsA201 cells and Xenopus
      oocytes) because of the unavailability of alpha1D-specific modulators. alpha1D
      I(Ca-L) activated at negative potentials (between -60 and -50 mV). Positive IgG
      inhibited alpha1D I(Ca-L) in both expression systems. This inhibition was rescued
      by a Ca channel activator, Bay K8644. No effect on alpha1D I(Ca-L) was observed
      with negative IgG and denatured positive IgG. Western blot data showed that
      positive IgG binds directly to alpha1D Ca channel protein. CONCLUSIONS: The data
      are the first to demonstrate (1) expression of the alpha1D Ca channel in human
      fetal heart, (2) inhibition of alpha1D I(Ca-L) by positive IgG, and (3) direct
      cross-reactivity of positive IgG with the alpha1D Ca channel protein. Given that
      alpha1D I(Ca-L) activates at voltages within the pacemaker's diastolic
      depolarization, inhibition of alpha1D I(Ca-L) in part may account for autoimmune
      associated sinus bradycardia. In addition, Bay K8644 rescue of alpha1D I(Ca-L)
      inhibition opens new directions in the development of pharmacotherapeutic
      approaches in the management of CHB.

PMID- 15939814
TI  - D-4F induces heme oxygenase-1 and extracellular superoxide dismutase, decreases
      endothelial cell sloughing, and improves vascular reactivity in rat model of
      diabetes.
AB  - BACKGROUND: Apolipoprotein A1 mimetic peptide, synthesized from D-amino acid (D
      4F), enhances the ability of HDL to protect LDL against oxidation in
      atherosclerotic animals. METHODS AND RESULTS: We investigated the mechanisms by
      which D-4F provides antioxidant effects in a diabetic model. Sprague-Dawley rats
      developed diabetes with administration of streptozotocin (STZ). We examined the
      effects of daily D-4F (100 microg/100 g of body weight, intraperitoneal
      injection) on superoxide (O2-), extracellular superoxide dismutase (EC-SOD),
      vascular heme oxygenase (HO-1 and HO-2) levels, and circulating endothelial cells
      in diabetic rats. In response to D-4F, both the quantity and activity of HO-1
      were increased. O2- levels were elevated in diabetic rats (74.8+/-8x10(3) cpm/10
      mg protein) compared with controls (38.1+/-8x10(3) cpm/10 mg protein; P<0.01). D
      4F decreased O2- levels to 13.23+/-1x10(3) (P<0.05 compared with untreated
      diabetics). The average number of circulating endothelial cells was higher in
      diabetics (50+/-6 cells/mL) than in controls (5+/-1 cells/mL) and was
      significantly decreased in diabetics treated with D-4F (20+/-3 cells/mL;
      P<0.005). D-4F also decreased endothelial cell fragmentation in diabetic rats.
      The impaired relaxation typical of blood vessels in diabetic rats was prevented
      by administration of D-4F (85.0+/-2.0% relaxation). Western blot analysis showed
      decreased EC-SOD in the diabetic rats, whereas D-4F restored the EC-SOD level.
      CONCLUSIONS: We conclude that an increase in circulating endothelial cell
      sloughing, superoxide anion, and vasoconstriction in diabetic rats can be
      prevented by administration of D-4F, which is associated with an increase in 2
      antioxidant proteins, HO-1 and EC-SOD.

PMID- 15939815
TI  - Calcineurin-nuclear factor of activated T cells pathway-dependent cardiac
      remodeling in mice deficient in guanylyl cyclase A, a receptor for atrial and
      brain natriuretic peptides.
AB  - BACKGROUND: Although disruption of guanylyl cyclase (GC) A, a natriuretic peptide
      receptor, induces cardiac hypertrophy and fibrosis, the molecular mechanism
      underlying these effects are not well understood. In this study, we examined the
      role of calcineurin, a calcium-dependent phosphatase, in cardiac remodeling in
      GCA-knockout (GCA-KO) mice. METHODS AND RESULTS: At 14 weeks of age, calcineurin
      activity, nuclear translocation of nuclear factor of activated T cells c3
      (NFATc3), and modulatory calcineurin-interacting protein 1 (MCIP1) gene
      expressions were increased in the hearts of GCA-KO mice compared with wild-type
      (WT) mice. Blockade of calcineurin activation by FK506 (6 mg/kg body weight
      administered subcutaneously once a day from 10 to 14 weeks of age) significantly
      decreased the heart-to-body weight ratio, cardiomyocyte size, and collagen volume
      fraction in GCA-KO mice, whereas FK506 did not affect these parameters in WT
      mice. Overexpression of atrial and brain natriuretic peptides, collagen, and
      fibronectin mRNAs in GCA-KO mice was also attenuated by FK506. Electrophoretic
      mobility shift assays demonstrated that GATA4 DNA-binding activity was increased
      in GCA-KO mice, and this increase was inhibited by calcineurin blockade. In
      neonatal cultured cardiac myocytes, inhibition of GCA by HS142-1 (100 microg/mL)
      increased basal and phenylephrine (10(-6) mol/L)-stimulated calcineurin activity,
      nuclear translocation of NFATc3, and MCIP1 mRNA expression. In contrast,
      activation of GCA by atrial natriuretic peptide (10(-6) mol/L) inhibited
      phenylephrine (10(-6) mol/L)-stimulated nuclear translocation of NFATc3.
      CONCLUSIONS: These results suggest that activation of cardiac GCA by locally
      secreted natriuretic peptides protects the heart from excessive cardiac
      remodeling by inhibiting the calcineurin-NFAT pathway.

PMID- 15939816
TI  - Cholesterol feeding increases C-reactive protein and serum amyloid A levels in
      lean insulin-sensitive subjects.
AB  - BACKGROUND: Inflammatory markers associated with elevated cardiovascular risk are
      increased by cholesterol feeding in animal models. However, whether dietary
      cholesterol increases inflammatory marker levels in humans is not known. METHODS
      AND RESULTS: C-reactive protein (CRP), serum amyloid A (SAA), and lipoprotein
      levels were compared in 201 healthy subjects on an American Heart Association
      National Cholesterol Education Program step 1 diet at baseline and after addition
      of 4 eggs per day for 4 weeks. Subjects were classified a priori into 3 groups
      based on their body mass index (BMI) and insulin sensitivity index (SI): lean
      insulin sensitive (LIS), mean+/-SEM BMI, 23.2+/-0.3 kg/m2, and SI, 6.7+/-0.3x10(
      4)min(-1)/(microU/mL), n=66; lean insulin resistant (LIR), BMI, 24.5+/-0.2 kg/m2
      and SI, 2.9+/-0.1x10(-4)min(-1)/(microU/mL), n=76; or obese insulin resistant
      (OIR), BMI, 31.4+/-0.5 kg/m2 and SI, 2.1+/-0.1x10(-4)min(-1)/(microU/mL), n=59.
      Insulin resistance and obesity each were associated with increased baseline
      levels of both CRP (P for trend, <0.001) and SAA (P for trend=0.015). Egg feeding
      was associated with significant increases in both CRP and SAA in the LIS group
      (both P<0.01) but not in the LIR or OIR groups. Egg feeding also was associated
      with a significant increase in non-HDL cholesterol (P<0.001) in LIS subjects;
      however, there was no correlation between the change in non-HDL cholesterol or
      changes in either CRP or SAA in this group. CONCLUSIONS: A high-cholesterol diet
      leads to significant increases in both inflammatory markers and non-HDL
      cholesterol levels in insulin-sensitive individuals but not in lean or obese
      insulin-resistant subjects.

PMID- 15939817
TI  - Conditional mineralocorticoid receptor expression in the heart leads to life
      threatening arrhythmias.
AB  - BACKGROUND: Life-threatening cardiac arrhythmia is a major source of mortality
      worldwide. Besides rare inherited monogenic diseases such as long-QT or Brugada
      syndromes, which reflect abnormalities in ion fluxes across cardiac ion channels
      as a final common pathway, arrhythmias are most frequently acquired and
      associated with heart disease. The mineralocorticoid hormone aldosterone is an
      important contributor to morbidity and mortality in heart failure, but its
      mechanisms of action are incompletely understood. METHODS AND RESULTS: To
      specifically assess the role of the mineralocorticoid receptor (MR) in the heart,
      in the absence of changes in aldosteronemia, we generated a transgenic mouse
      model with conditional cardiac-specific overexpression of the human MR. Mice
      exhibit a high rate of death prevented by spironolactone, an MR antagonist used
      in human therapy. Cardiac MR overexpression led to ion channel remodeling,
      resulting in prolonged ventricular repolarization at both the cellular and
      integrated levels and in severe ventricular arrhythmias. CONCLUSIONS: Our results
      indicate that cardiac MR triggers cardiac arrhythmias, suggesting novel
      opportunities for prevention of arrhythmia-related sudden death.

PMID- 15939818
TI  - Does autonomic function link social position to coronary risk? The Whitehall II
      study.
AB  - BACKGROUND: Laboratory and clinical studies suggest that the autonomic nervous
      system responds to chronic behavioral and psychosocial stressors with adverse
      metabolic consequences and that this may explain the relation between low social
      position and high coronary risk. We sought to test this hypothesis in a healthy
      occupational cohort. METHODS AND RESULTS: This study comprised 2197 male civil
      servants 45 to 68 years of age in the Whitehall II study who were undergoing
      standardized assessments of social position (employment grade) and the
      psychosocial, behavioral, and metabolic risk factors for coronary disease
      previously found to be associated with low social position. Five-minute
      recordings of heart rate variability (HRV) were used to assess cardiac
      parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to
      0.40 Hz]) and the influence of sympathetic and parasympathetic function (low
      frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low
      HRV (age-adjusted trend for each modality, P< or =0.02). Adverse behavioral
      factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job
      control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted
      mean low-frequency power was 319 ms2 among those participants in the bottom
      tertile of job control compared with 379 ms2 in the other participants (P=0.004).
      HRV showed strong (P<0.001) linear associations with components of the metabolic
      syndrome (waist circumference, systolic blood pressure, HDL cholesterol,
      triglycerides, and fasting and 2-hour postload glucose). The social gradient in
      prevalence of metabolic syndrome was explained statistically by adjustment for
      low-frequency power, behavioral factors, and job control. CONCLUSIONS:
      Chronically impaired autonomic function may link social position to different
      components of coronary risk in the general population.

PMID- 15939819
TI  - Apolipoprotein E mimetic Peptide dramatically lowers plasma cholesterol and
      restores endothelial function in watanabe heritable hyperlipidemic rabbits.
AB  - BACKGROUND: These studies were designed to determine whether the dual-domain
      peptide with a class A amphipathic helix linked to the receptor-binding domain of
      apolipoprotein (apo) E (Ac-hE-18A-NH2) possesses both antidyslipidemic and
      antiinflammatory properties. METHODS AND RESULTS: A single bolus (15 mg/kg IV) of
      Ac-hE-18A-NH2 that contains LRKLRKRLLR (141- to 150-residue region of apo E)
      covalently linked to apo A-I mimetic peptide 18A not only reduced plasma
      cholesterol levels (baseline, 562+/-29.0 mg/dL versus 287.7+/-22.0 mg/dL at 18
      hours, P<0.001) in the Watanabe heritable hyperlipidemic rabbit model but also
      significantly improved arterial endothelial function. This improvement was
      associated with a reduction in 2 markers of oxidative stress. First, the plasma
      lipid hydroperoxide content was reduced significantly, an effect associated with
      a 5-fold increase in HDL paraoxonase activity. Second, the formation of
      superoxide anion, a scavenger of nitric oxide, was also significantly reduced in
      arteries of these animals. CONCLUSIONS: Because dyslipidemia and endothelial
      dysfunction are common features of the atherosclerotic disease process, this
      unique dual-domain peptide has ideal composite properties that ameliorate key
      contributory factors to atherosclerosis.

PMID- 15939820
TI  - Long-term survival after acute myocardial infarction is lower in more deprived
      neighborhoods.
AB  - BACKGROUND: As part of the Worcester Heart Attack Study, a community-wide study
      examining changes over time in the incidence and long-term case-fatality rates of
      greater Worcester, Mass, residents hospitalized with confirmed acute myocardial
      infarction (AMI), we investigated the hypothesis that census tract-level
      socioeconomic position is an important predictor of survival after hospital
      discharge for AMI, after adjusting for demographic and clinical characteristics.
      METHODS AND RESULTS: Data were available for 3423 confirmed cases of AMI among
      metropolitan Worcester residents during the 4 study years of 1995, 1997, 1999,
      and 2001 who were followed up through the end of 2002. The mean age among
      patients was 69 years, and 58% were men. Using a multilevel Cox proportional
      hazards regression model, we estimated a 30% higher death rate after AMI for
      patients living in census tracts with the most residents living below the poverty
      line compared with patients living in the wealthiest census tracts (relative
      risk=1.30; 95% CI, 1.08 to 1.56). Similarly, patients living in census tracts
      with the highest proportion of residents with less than a high school education
      experienced a 47% higher death rate than patients living in census tracts with
      the lowest proportion of residents with less than a high school education
      (relative risk=1.47; 95% CI, 1.15 to 1.88). CONCLUSIONS: Within a medium-sized
      urban area, there are important variations in survival after hospital discharge
      for AMI that are associated with socioeconomic position. These associations
      persist after adjustment for demographic and clinical characteristics. Reasons
      for these differences warrant further investigation.

PMID- 15939821
TI  - Long-term response to calcium channel blockers in idiopathic pulmonary arterial
      hypertension.
AB  - BACKGROUND: Characteristics of patients with idiopathic pulmonary arterial
      hypertension (IPAH) who benefit from long-term calcium channel blockers (CCB) are
      unknown. METHODS AND RESULTS: Acute pulmonary vasodilator testing with
      epoprostenol or nitric oxide was performed in 557 IPAH patients. Acute
      responders, defined by a fall in both mean pulmonary artery pressure (PAP) and
      pulmonary vascular resistance (PVR) >20%, received long-term oral CCB. Patients
      who benefit from long-term CCB were defined as those being in New York Heart
      Association (NYHA) functional class I or II after at least 1 year on CCB
      monotherapy. Among the 70 patients who displayed acute pulmonary vasoreactivity
      (12.6%; 95% CI, 9.8% to 15.3%) and received CCB therapy, only 38 showed long-term
      improvement (6.8%; 95% CI, 4.7% to 8.9%). Long-term CCB responders had less
      severe disease at baseline than patients who failed. During acute vasodilator
      testing, long-term CCB responders displayed a more pronounced fall in mean PAP (
      39+/-11% versus -26+/-7%; P<0.0001), reaching an absolute value of mean PAP lower
      than that measured in patients who failed (33+/-8 versus 46+/-10 mm Hg;
      P<0.0001). After 7.0+/-4.1 years, all but 1 long-term CCB responders were alive
      in NYHA class I or II, with a sustained hemodynamic improvement. In the group of
      patients who failed on CCB, the 5-year survival rate was 48%. CONCLUSIONS: Long
      term CCB responders represent <10% of IPAH patients evaluated in a pulmonary
      vascular referral center. During acute vasodilator testing, these patients showed
      significantly lower levels of both mean PAP and PVR, which reached near-normal
      values.

PMID- 15939822
TI  - Three-dimensional electroanatomic voltage mapping increases accuracy of
      diagnosing arrhythmogenic right ventricular cardiomyopathy/dysplasia.
AB  - BACKGROUND: Three-dimensional electroanatomic voltage mapping offers the
      potential to identify low-voltage areas that correspond to regions of right
      ventricular (RV) myocardial loss and fibrofatty replacement in patients with
      arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). METHODS AND RESULTS: Thirty
      one consecutive patients (22 men and 9 women; mean age, 30.8+/-7 years) who
      fulfilled the criteria of the Task Force of the European Society of Cardiology
      and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D
      diagnosis after noninvasive clinical evaluation underwent further invasive study
      including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to
      validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175+/-23)
      were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal
      RV electroanatomic voltage mapping showing > or =1 area (mean 2.25+/-0.7) with
      low-voltage values (bipolar electrogram amplitude <0.5 mV), surrounded by a
      border zone (0.5 to 1.5 mV) that transitioned into normal myocardium (>1.5 mV).
      Low-voltage electrograms appeared fractionated with significantly prolonged
      duration and delayed activation. In 11 patients (group B; 35%), electroanatomic
      voltage mapping was normal, with preserved electrogram voltage (4.4+/-0.7 mV) and
      duration (37.2+/-0.9 ms) throughout the RV. Low-voltage areas in patients from
      group A corresponded to echocardiographic/angiographic RV wall motion
      abnormalities and were significantly associated with myocyte loss and fibrofatty
      replacement at EMB (P<0.0001) and familial ARVC/D (P<0.0001). Patients from group
      B had sporadic disease and histopathological evidence of inflammatory
      cardiomyopathy (P<0.0001). During the time interval from onset of symptoms to the
      invasive study, 11 patients (55%) with electroanatomic low-voltage regions
      received an implantable cardioverter/defibrillator because of life-threatening
      ventricular arrhythmias, whereas all but 1 patient with a normal voltage map
      remained stable on antiarrhythmic drug therapy (P=0.02). CONCLUSIONS: Three
      dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing
      ARVC/D (1) by demonstrating low-voltage areas that were associated with
      fibrofatty myocardial replacement and (2) by identifying a subset of patients who
      fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved
      electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a
      better arrhythmic outcome.

PMID- 15939823
TI  - Association of osteoprotegerin with human abdominal aortic aneurysm progression.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is characterized by destruction of
      the arterial media associated with loss of vascular smooth muscle cells,
      infiltration of mononuclear cells, and high concentration of metalloproteinases
      (MMPs) and cytokines. Osteoprotegerin (OPG) has recently been identified in
      atherosclerosis. The presence and functional importance of OPG in human AAA was
      investigated. METHODS AND RESULTS: In 146 men with small AAA followed up by
      ultrasound for 3 years, serum OPG was weakly correlated with aneurysm growth
      rate. Western analysis showed 3-, 8-, and 12-fold-greater OPG concentrations in
      human AAA biopsies compared with biopsies of atherosclerotic narrowed aorta
      (1.4+/-0.1 versus 0.5+/-0.1 ng/mg tissue; P=0.002), postmortem nondiseased
      abdominal aorta (1.4+/-0.1 versus 0.2+/-0.1 ng/mg tissue; P<0.001), and
      nondiseased thoracic aorta (1.4+/-0.1 versus 0.1+/-0.06 ng/mg tissue; P<0.001).
      Healthy human aortic vascular smooth muscle cells incubated with recombinant
      human (rh)OPG (0 to 20 ng rhOPG/10(5) cells per 1 mL per 24 hours) developed an
      aneurysmal phenotype defined by impaired cell proliferation (P<0.001), increased
      apoptosis (P<0.01), and increased MMP-9 (92 kDa) expression (P<0.001). Incubation
      of monocytic THP-1 cells with 1 ng rhOPG/10(5) cells per 1 mL per 24 hours
      induced a 2-fold increase in MMP-9 expression (P<0.001), a 1.5-fold increase in
      MMP-2 activity (P=0.005), and a 2-fold stimulation of IL-6 production in these
      cells (P=0.02). Finally, secretion of OPG from human AAA explant was abrogated by
      treatment with the angiotensin II blocker irbesartan, with the reduction in
      secreted levels averaging 63.0+/-0.9 ng/mg tissue per 48-hour period.
      CONCLUSIONS: These findings support a role for OPG in the growth of human AAA and
      suggest a potential benefit for angiotensin II blockade in slowing aneurysm
      expansion.

PMID- 15939824
TI  - Images in cardiovascular medicine. Spontaneous left atrial dissection presenting
      as pulmonary edema.

PMID- 15939825
TI  - Images in cardiovascular medicine. ST elevation during open heart surgery:
      floating air bubble in saphenous vein graft.

PMID- 15939826
TI  - Images in cardiovascular medicine. Fluorine-18-labeled deoxyglucose positron
      emission tomography in the diagnosis and management of aortitis with pulmonary
      artery involvement.

PMID- 15939827
TI  - Letter regarding article by Devereux et al, "regression of hypertensive left
      ventricular hypertrophy by losartan compared with atenolol: the Losartan
      Intervention for Endpoint Reduction in Hypertension (LIFE) trial".

PMID- 15939828
TI  - Letter regarding article by Thijssen et al, "temporal and spatial variations in
      structural protein expression during the progression from stunned to hibernating
      myocardium".

PMID- 15939829
TI  - Comparing different strategies for catheter ablation of atrial fibrillation.

PMID- 15939830
TI  - Particulate pollution and endothelial function: deja vu all over again in the
      air.

PMID- 15939831
TI  - Alpha-linolenic acid: a gift from the land?

PMID- 15939832
TI  - Endothelium-derived nitric oxide regulates postischemic myocardial oxygenation
      and oxygen consumption by modulation of mitochondrial electron transport.
AB  - BACKGROUND: Nitric oxide (NO) production is increased in postischemic myocardium,
      and NO can control mitochondrial oxygen consumption in vitro. Therefore, we
      investigated the role of endothelial NO synthase (eNOS)-derived NO on in vivo
      regulation of oxygen consumption in the postischemic heart. METHODS AND RESULTS:
      Mice were subjected to 30 minutes of coronary ligation followed by 60 minutes of
      reperfusion. Myocardial oxygen tension (Po2) was monitored by electron
      paramagnetic resonance oximetry. In wild-type, N-nitro-L-arginine methyl ester (L
      NAME)-treated (with 1 mg/mL in drinking water), and eNOS knockout (eNOS-/-) mice,
      no difference was observed among baseline myocardial Po2 values (8.6+/-0.7,
      10.0+/-1.2, and 10.1+/-1.2 mm Hg, respectively) or those measured at 30 minutes
      of ischemia (1.4+/-0.6, 2.3+/-0.9, and 3.1+/-1.4 mm Hg, respectively). After
      reperfusion, myocardial Po2 increased markedly (P<0.001 versus baseline in each
      group) but was much lower in L-NAME-treated and eNOS-/- mice (17.4+/-1.6 and
      20.4+/-1.9 mm Hg) than in wild-type mice (46.5+/-1.7 mm Hg; P<0.001). A transient
      peak of myocardial Po2 was observed at early reperfusion in wild-type mice. No
      reactive hyperemia was observed during early reperfusion. Endothelial NO
      decreased the rate-pressure product (P<0.05), upregulated cytochrome c oxidase
      (CcO) mRNA expression (P<0.01) with no change in CcO activity, and inhibited NADH
      dehydrogenase (NADH-DH) activity (P<0.01) without alteration of NADH-DH mRNA
      expression. Peroxynitrite-mediated tyrosine nitration was higher in hearts from
      wild-type mice than in eNOS-/- or L-NAME-treated hearts. CONCLUSIONS: eNOS
      derived NO markedly suppresses in vivo O2 consumption in the postischemic heart
      through modulation of mitochondrial respiration based on alterations in enzyme
      activity and mRNA expression of NADH-DH and CcO. The marked myocardial
      hyperoxygenation in reperfused myocardium may be a critical factor that triggers
      postischemic remodeling.

PMID- 15939833
TI  - Neurocardiogenic syncope and related disorders of orthostatic intolerance.

PMID- 15939834
TI  - Recommendations of the National Heart, Lung, and Blood Institute Working Group on
      Future Direction in Cardiac Surgery.
AB  - New surgical procedures, imaging modalities, and medical devices have improved
      therapy for many patients and made treatment possible for others who have had few
      options in the past. In February 2004, the National Heart, Lung, and Blood
      Institute's (NHLBI) Advisory Council proposed that the institute evaluate the
      status and future directions in cardiac surgery. In response to this
      recommendation, the NHLBI convened a working group of cardiac surgeons on May 7
      and 8, 2004, to assess the state of cardiac surgery research, identify critical
      gaps in current knowledge, determine areas of opportunity, and obtain specific
      recommendations for future research activities. The working group discussed
      surgical revascularization, novel surgical approaches, valvular research
      directions, biotechnology and cell-based therapy, heart failure, imaging
      modalities, and barriers to clinical research and presents its recommendations
      here.

PMID- 15939835
TI  - Hypnotic session.

PMID- 15939836
TI  - Psychiatric epidemiology: it's not just about counting anymore.

PMID- 15939837
TI  - Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the
      National Comorbidity Survey Replication.
AB  - CONTEXT: Little is known about lifetime prevalence or age of onset of DSM-IV
      disorders. OBJECTIVE: To estimate lifetime prevalence and age-of-onset
      distributions of DSM-IV disorders in the recently completed National Comorbidity
      Survey Replication. DESIGN AND SETTING: Nationally representative face-to-face
      household survey conducted between February 2001 and April 2003 using the fully
      structured World Health Organization World Mental Health Survey version of the
      Composite International Diagnostic Interview. PARTICIPANTS: Nine thousand two
      hundred eighty-two English-speaking respondents aged 18 years and older. MAIN
      OUTCOME MEASURES: Lifetime DSM-IV anxiety, mood, impulse-control, and substance
      use disorders. RESULTS: Lifetime prevalence estimates are as follows: anxiety
      disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%;
      substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much
      earlier for anxiety (11 years) and impulse-control (11 years) disorders than for
      substance use (20 years) and mood (30 years) disorders. Half of all lifetime
      cases start by age 14 years and three fourths by age 24 years. Later onsets are
      mostly of comorbid conditions, with estimated lifetime risk of any disorder at
      age 75 years (50.8%) only slightly higher than observed lifetime prevalence
      (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in
      earlier cohorts and have fairly stable intercohort differences across the life
      course that vary in substantively plausible ways among sociodemographic
      subgroups. CONCLUSIONS: About half of Americans will meet the criteria for a DSM
      IV disorder sometime in their life, with first onset usually in childhood or
      adolescence. Interventions aimed at prevention or early treatment need to focus
      on youth.

PMID- 15939838
TI  - Failure and delay in initial treatment contact after first onset of mental
      disorders in the National Comorbidity Survey Replication.
AB  - CONTEXT: An understudied crucial step in the help-seeking process is making
      prompt initial contact with a treatment provider after first onset of a mental
      disorder. OBJECTIVE: To provide data on patterns and predictors of failure and
      delay in making initial treatment contact after first onset of a mental disorder
      in the United States from the recently completed National Comorbidity Survey
      Replication. DESIGN AND SETTING: Nationally representative face-to-face household
      survey carried out between February 2001 and April 2003. PARTICIPANTS: A total of
      9282 respondents aged 18 years and older. MAIN OUTCOME MEASURES: Lifetime DSM-IV
      disorders were assessed with the World Mental Health (WMH) Survey Initiative
      version of the World Health Organization Composite International Diagnostic
      Interview (WMH-CIDI), a fully structured interview designed to be administered by
      trained lay interviewers. Information about age of first professional treatment
      contact for each lifetime DSM-IV/WMH-CIDI disorder assessed in the survey was
      collected and compared with age at onset of the disorder to study typical
      duration of delay. RESULTS: Cumulative lifetime probability curves show that the
      vast majority of people with lifetime disorders eventually make treatment
      contact, although more so for mood (88.1%-94.2%) disorders than for anxiety
      (27.3%-95.3%), impulse control (33.9%-51.8%), or substance (52.7%-76.9%)
      disorders. Delay among those who eventually make treatment contact ranges from 6
      to 8 years for mood disorders and 9 to 23 years for anxiety disorders. Failure to
      make initial treatment contact and delay among those who eventually make
      treatment contact are both associated with early age of onset, being in an older
      cohort, and a number of socio-demographic characteristics (male, married, poorly
      educated, racial/ethnic minority). CONCLUSIONS: Failure to make prompt initial
      treatment contact is a pervasive aspect of unmet need for mental health care in
      the United States. Interventions to speed initial treatment contact are likely to
      reduce the burdens and hazards of untreated mental disorder.

PMID- 15939840
TI  - Twelve-month use of mental health services in the United States: results from the
      National Comorbidity Survey Replication.
AB  - BACKGROUND: Dramatic changes have occurred in mental health treatments during the
      past decade. Data on recent treatment patterns are needed to estimate the unmet
      need for services. OBJECTIVE: To provide data on patterns and predictors of 12
      month mental health treatment in the United States from the recently completed
      National Comorbidity Survey Replication. DESIGN AND SETTING: Nationally
      representative face-to-face household survey using a fully structured diagnostic
      interview, the World Health Organization's World Mental Health Survey Initiative
      version of the Composite International Diagnostic Interview, carried out between
      February 5, 2001, and April 7, 2003. PARTICIPANTS: A total of 9282 English
      speaking respondents 18 years and older. MAIN OUTCOME MEASURES: Proportions of
      respondents with 12-month DSM-IV anxiety, mood, impulse control, and substance
      disorders who received treatment in the 12 months before the interview in any of
      4 service sectors (specialty mental health, general medical, human services, and
      complementary and alternative medicine). Number of visits and proportion of
      patients who received minimally adequate treatment were also assessed. RESULTS:
      Of 12-month cases, 41.1% received some treatment in the past 12 months, including
      12.3% treated by a psychiatrist, 16.0% treated by a non-psychiatrist mental
      health specialist, 22.8% treated by a general medical provider, 8.1% treated by a
      human services provider, and 6.8% treated by a complementary and alternative
      medical provider (treatment could be received by >1 source). Overall, cases
      treated in the mental health specialty sector received more visits (median, 7.4)
      than those treated in the general medical sector (median, 1.7). More patients in
      specialty than general medical treatment also received treatment that exceeded a
      minimal threshold of adequacy (48.3% vs 12.7%). Unmet need for treatment is
      greatest in traditionally underserved groups, including elderly persons, racial
      ethnic minorities, those with low incomes, those without insurance, and residents
      of rural areas. CONCLUSIONS: Most people with mental disorders in the United
      States remain either untreated or poorly treated. Interventions are needed to
      enhance treatment initiation and quality.

PMID- 15939839
TI  - Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the
      National Comorbidity Survey Replication.
AB  - BACKGROUND: Little is known about the general population prevalence or severity
      of DSM-IV mental disorders. OBJECTIVE: To estimate 12-month prevalence, severity,
      and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders
      in the recently completed US National Comorbidity Survey Replication. DESIGN AND
      SETTING: Nationally representative face-to-face household survey conducted
      between February 2001 and April 2003 using a fully structured diagnostic
      interview, the World Health Organization World Mental Health Survey Initiative
      version of the Composite International Diagnostic Interview. PARTICIPANTS: Nine
      thousand two hundred eighty-two English-speaking respondents 18 years and older.
      MAIN OUTCOME MEASURES: Twelve-month DSM-IV disorders. RESULTS: Twelve-month
      prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%;
      substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were
      classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent
      carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses.
      Latent class analysis detected 7 multivariate disorder classes, including 3
      highly comorbid classes representing 7% of the population. CONCLUSION: Although
      mental disorders are widespread, serious cases are concentrated among a
      relatively small proportion of cases with high comorbidity.

PMID- 15939841
TI  - Operation of the schizophrenia susceptibility gene, neuregulin 1, across
      traditional diagnostic boundaries to increase risk for bipolar disorder.
AB  - CONTEXT: Family and twin data suggest that, in addition to susceptibility genes
      specific for bipolar disorder or schizophrenia, genes exist that contribute to
      susceptibility across the traditional kraepelinian divide. Several studies have
      provided evidence that variation at the neuregulin 1 (NRG1) gene on chromosome
      8p12 influences susceptibility to schizophrenia. The most consistent finding has
      been that one particular haplotype (the "core" haplotype) is overrepresented in
      cases compared with control subjects. OBJECTIVE: To investigate the possible role
      of NRG1 in bipolar disorder. DESIGN: Genetic case-control association analysis.
      SETTING: Subjects were unrelated and ascertained from general psychiatric
      inpatient and outpatient services. PARTICIPANTS: Five hundred twenty-nine
      patients with DSM-IV bipolar I disorder and 1011 controls from the United Kingdom
      (100% white). METHODS: We genotyped the markers constituting the NRG1 core
      haplotype in cases and controls and reanalyzed our existing data from 573 DSM-IV
      schizophrenia cases with this larger set of controls. RESULTS: We found a
      significant difference in haplotype distribution between bipolar cases and
      controls globally (P = .003) and specifically for the core haplotype. Frequencies
      were 10.2% for bipolar cases and 7.8% for controls (effect size, as measured by
      odds ratio [OR], 1.37; 95% confidence interval [CI], 1.03-1.80; P = .04). The
      effect size in our bipolar sample was similar to that in our schizophrenia sample
      (OR, 1.22; 95% CI, 0.92-1.61). In the bipolar cases with predominantly mood
      incongruent psychotic features (n = 193), the effect was greater (OR, 1.71; 95%
      CI, 1.29-2.59; P = .009), as was the case in the subset of schizophrenia cases (n
      = 27) who had experienced mania (OR, 1.64; 95% CI, 0.54-5.01). CONCLUSIONS: Our
      findings suggest that neuregulin 1 plays a role in influencing susceptibility to
      bipolar disorder and schizophrenia and that it may exert a specific effect in the
      subset of functional psychosis that has manic and mood-incongruent psychotic
      features.

PMID- 15939842
TI  - Effects of cigarette smoking on spatial working memory and attentional deficits
      in schizophrenia: involvement of nicotinic receptor mechanisms.
AB  - BACKGROUND: Cigarette smoking rates in schizophrenia are higher than in the
      general population. OBJECTIVES: To determine whether cigarette smoking modifies
      cognitive deficits in schizophrenia and to establish the role of nicotinic
      acetylcholine receptors (nAChRs) in mediating cigarette smoking-related cognitive
      enhancement. DESIGN: Neuropsychological assessments were performed at smoking
      baseline, after overnight abstinence, and after smoking reinstatement across 3
      separate test weeks during which subjects were pretreated in a counterbalanced
      manner with the nonselective nAChR antagonist mecamylamine hydrochloride (0, 5,
      or 10 mg/d). PARTICIPANTS: Twenty-five smokers with schizophrenia and 25 control
      smokers. SETTING: Outpatient mental health center. MAIN OUTCOME MEASURES:
      Visuospatial working memory (VSWM) and Continuous Performance Test (CPT) scores.
      RESULTS: In smokers with schizophrenia and control smokers, overnight abstinence
      led to undetectable plasma nicotine levels and an increase in tobacco craving.
      While abstinence reduced CPT hit rate in both groups, VSWM was only impaired in
      smokers with schizophrenia. Smoking reinstatement reversed abstinence-induced
      cognitive impairment. Enhancement of VSWM and CPT performance by smoking
      reinstatement in smokers with schizophrenia, but not the subjective effects of
      smoking, was blocked by mecamylamine treatment. CONCLUSIONS: Cigarette smoking
      may selectively enhance VSWM and attentional deficits in smokers with
      schizophrenia, which may depend on nAChR stimulation. These findings may have
      implications for understanding the high rates of smoking in schizophrenia and for
      developing pharmacotherapies for cognitive deficits and nicotine dependence in
      schizophrenia.

PMID- 15939843
TI  - Depression and heart rate variability in patients with stable coronary heart
      disease: findings from the Heart and Soul Study.
AB  - CONTEXT: Depression is associated with low heart rate variability (HRV) in
      patients following myocardial infarction, suggesting that alterations in the
      autonomic nervous system may contribute to the adverse cardiac outcomes
      associated with depression. Whether depression is associated with low HRV in
      patients with stable coronary heart disease (CHD) is not known. OBJECTIVE: To
      examine the association between major depression and 24-hour HRV in patients with
      stable CHD. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 873
      outpatients with stable CHD recruited from outpatient clinics in the San
      Francisco Bay Area, California. MAIN OUTCOME MEASURES: Major depression was
      assessed using the Computerized National Institute of Mental Health Diagnostic
      Interview Schedule. Heart rate variability was measured by 24-hour ambulatory
      electrocardiography. RESULTS: A total of 195 participants (22%) had major
      depression. Overall, we observed no association between depression and HRV as
      measured by time domain or frequency domain variables. Mean HRV was similar in
      participants with and without depression (all P values >.10), and participants
      with depression were no more likely than those without depression to have low HRV
      (all P values >.10). CONCLUSIONS: We found no evidence of an association between
      depression and HRV in 873 outpatients with stable CHD. These findings raise
      questions about the potential role of HRV in the association between depression
      and cardiovascular disease.

PMID- 15939844
TI  - Cognitive modulation of the endocrine stress response to a pharmacological
      challenge in normal and panic disorder subjects.
AB  - CONTEXT: The hypothalamic-pituitary-adrenal (HPA) axis may mediate the
      deleterious effects of stress on health. It is sensitive to cognitive and
      emotional aspects of organism-environment interactions, such as familiarity,
      control, and social support. Scientific study of how such factors moderate human
      HPA axis activity has been limited. Their relevance to HPA axis disturbances in
      psychiatric patients is largely unexplored. OBJECTIVE: To determine whether
      cognitive manipulation can alter HPA axis activity in laboratory studies and
      whether patients with panic disorder are differentially sensitive to the
      manipulated factors. DESIGN: Pharmacological activation paradigm (cholecystokinin
      B agonist pentagastrin) by which we examined symptom and endocrine effects on
      subjects randomly assigned to a standard introduction or a cognitive
      intervention. SETTING: Clinical research center. PARTICIPANTS: Recruited from
      university clinic and newspaper advertisements. Fourteen patients with panic
      disorder and 14 controls, individually matched for age and sex. Intervention Half
      of each group received a 9-minute cognitive intervention designed to reduce
      novelty, increase cognitive coping, and provide a sense of control. MAIN OUTCOME
      MEASURES: Corticotropin (ACTH) and cortisol levels. RESULTS: The cognitive
      intervention significantly reduced cortisol (P = .02) and ACTH (P = .01) levels,
      despite pentagastrin's robust stimulation of both hormones (P<.001). The
      intervention effect was evident in patients and controls, who did not differ in
      basal HPA axis activity or response to pentagastrin. They did differ in panic
      symptom responses, which were unaffected by the intervention, and in ACTH effects
      of the intervention. Patients' exaggerated anxiety responses to pentagastrin were
      normalized by the intervention. CONCLUSIONS: Cognitive/emotional manipulation can
      substantially modulate HPA axis responses to pharmacological activation in
      humans, and HPA disturbances in panic disorder may be secondary to manipulable
      cognitive/emotional sensitivities. Further study of such factors as novelty,
      control, and coping may help clarify the origins of HPA axis disturbance in
      psychiatric disorders and the mediators linking psychosocial stress to disease.

PMID- 15939845
TI  - Effect of genes, environment, and lifetime co-occurring disorders on health
      related quality of life in problem and pathological gamblers.
AB  - BACKGROUND: Problem and pathological gambling are associated with many
      impairments in quality of life, including financial, family, legal, and social
      problems. Gambling disorders commonly co-occur with other psychiatric disorders,
      such as alcoholism and depression. Although these consequences and correlates
      have been reported, little is known about the health-related functional
      impairment associated with gambling. OBJECTIVE: To model differences in the
      health-related quality of life (HRQoL) among non-problem gamblers, problem
      gamblers, and pathological gamblers after controlling for lifetime co-occurring
      substance use disorders, psychiatric disorders, sociodemographics, and genetic
      and family environmental influences. DESIGN: Cohort and co-twin studies. SETTING:
      Nationally distributed community sample. PATIENTS: Male twin members of the
      Vietnam Era Twin Registry: 53 pathological gamblers, 270 subclinical problem
      gamblers, and 1346 non-problem gamblers (controls). INTERVENTIONS: We obtained
      HRQoL data, via the 8-Item Short-Form Health Survey, from all participants. Data
      from a subset of twin pairs discordant for gambling behavior was used to control
      for genetic and family environmental effects on HRQoL and problem gambling. Main
      Outcome Measure Health-related quality of life. RESULTS: Results from adjusted
      logistic regression analyses suggest little difference across groups in the
      physical domains of the health survey; however, for each mental health domain,
      pathological gamblers had lower HRQoL scores than problem gamblers (P<.05), who
      in turn had lower scores than non-problem gamblers (P<.05). After controlling for
      genes and family environment, no significant differences existed between the non
      problem gambling twins and their problem or pathological gambling brothers, but
      adjusted co-twin analyses resulted in statistically significant differences in 4
      of 8 subscales. CONCLUSIONS: Pathological and problem gambling are associated
      with significant decrements in HRQoL. This association is partly explained by
      genetic and family environmental effects and by lifetime co-occurring substance
      use disorders. Implications for clinicians, health care utilization, and public
      health issues are discussed.

PMID- 15939846
TI  - Sex differences in the clinical manifestations of Alzheimer disease pathology.
AB  - CONTEXT: Sex differences in risk of clinically diagnosed Alzheimer disease (AD)
      have been studied extensively, but little is known about the relation of the
      pathologic indices of AD to the clinical manifestations of the disease in men
      compared with women. OBJECTIVE: To test whether the relation of AD pathology to
      the clinical manifestations of the disease differs in men and women. DESIGN:
      Longitudinal, clinicopathologic cohort study. PARTICIPANTS AND SETTING: Analyses
      were conducted on 141 older Catholic clergy members who underwent detailed annual
      clinical evaluations and brain autopsy at death. The number of neuritic plaques,
      diffuse plaques, and neurofibrillary tangles in a 1-mm2 area sampled from 4
      cortical regions was counted, and a global measure of AD pathology (range, 0-2.98
      U) and specific measures of each pathology were derived. MAIN OUTCOME MEASURES:
      Clinical diagnosis of probable AD and level of global cognitive function at the
      last evaluation before death. RESULTS: Women had more global AD pathology than
      did men (P = .04), due primarily to more neurofibrillary tangles (P = .02). At
      the last evaluation before death, 57 persons met clinical criteria for probable
      AD (34 [60%] of them women). In logistic regression models, sex was not related
      to odds of clinical AD (odds ratio [OR], 1.35; 95% confidence interval [CI], 0.56
      3.25), but the relation of global AD pathology to clinical diagnosis differed for
      men and women. Each additional unit of AD pathology was associated with a nearly
      3-fold increase in the odds of clinical AD in men (OR, 2.82; 95% CI, 1.03-7.65)
      compared with a more than 20-fold increase in the odds of clinical AD in women
      (OR, 22.67; 95% CI, 5.11-100.53). Results were unchanged after controlling for
      potential confounders or using level of cognition as the outcome. CONCLUSION:
      These data suggest that AD pathology is more likely to be clinically expressed as
      dementia in women than in men.

PMID- 15939848
TI  - Associations of body mass index and perceived weight with suicide ideation and
      suicide attempts among US high school students.
AB  - BACKGROUND: Previous research with adolescents has shown associations of body
      weight and perceptions of body size with suicide ideation and suicide attempts,
      but it is unclear whether these associations are direct or whether a mediating
      effect exists. OBJECTIVES: To determine if body mass index and perceived weight
      are associated significantly with suicide ideation and suicide attempts,
      controlling for weight control practices, and if perceived weight mediates the
      associations of body mass index with suicide ideation and suicide attempts.
      DESIGN, SETTING, AND PARTICIPANTS: Data were analyzed from the 2001 Youth Risk
      Behavior Survey, a school-based survey administered to a nationally
      representative sample of students in grades 9 through 12 (N = 13 601). MAIN
      OUTCOME MEASURE: Self-reported past-year suicide ideation and suicide attempts,
      compared by perceived weight and body mass index category, calculated from self
      reported height and weight. RESULTS: Body mass index category was associated
      significantly with suicide ideation (among all students) and suicide attempts
      (among white and Hispanic students) without perceived weight in the model but not
      with perceived weight added to the model. In contrast with those who perceive
      themselves as about the right weight, students who perceived themselves as very
      underweight (odds ratio [OR], 2.29 [95% confidence interval (CI), 1.46-3.59]),
      slightly underweight (OR, 1.36 [95% CI, 1.03-1.79]), slightly overweight (OR,
      1.33 [95% CI, 1.12-1.58]), and very overweight (OR, 2.50 [95% CI, 1.73-3.60]) had
      greater adjusted odds of suicide ideation. Among white students, perceiving
      oneself as very underweight (OR, 3.04 [95% CI, 1.40-6.58]) or very overweight
      (OR, 2.74 [95% CI, 1.21-6.23]) was associated with greater odds of suicide
      attempts. Perceiving oneself as very underweight was associated with greater odds
      for suicide attempts among black (OR, 2.86 [95% CI, 1.10-7.45]) and Hispanic (OR,
      3.40 [95% CI, 1.54-7.51]) students. CONCLUSIONS: How adolescents perceive their
      body weight may be more important than their actual weight in terms of increased
      likelihood of suicidal behavior. Regardless of body mass index, extreme
      perceptions of weight appear to be significant risk factors for suicidal
      behavior; important racial/ethnic differences exist.

PMID- 15939849
TI  - Population demographic indicators associated with incidence of pyloric stenosis.
AB  - OBJECTIVES: To calculate incidence rates of pyloric stenosis (estimated by the
      rate of pyloromyotomy) among infants in Ontario and determine their association
      with population sociodemographic indicators. METHODS: Pyloromyotomy rates were
      calculated from hospital discharge data from 1993 through 2000. Four-year data
      (1993-1996 and 1997-2000) were combined to ensure the stability of the rates.
      Small-area variations in pyloromyotomy rates and correlations between
      sociodemographic indicators were studied. RESULTS: Approximately 84.0% of the
      patients were male infants (younger than 1 year). The sex-adjusted pyloromyotomy
      rates were 1.57 and 1.86 per 1000 with a 3.4-fold and 3.0-fold regional variation
      in 1993-1996 and 1997-2000, respectively. Urban areas consistently had the lowest
      pyloromyotomy rate (1.04 and 1.11 per 1000 in Metropolitan Toronto), but the
      highest rates were from more rural areas (3.30 and 3.38 per 1000 in Quinte,
      Kingston, Rideau). After adjusting for socioeconomic status and availability of
      surgeons in the region, living in a rural area remained a significant factor
      associated with a higher incidence of pyloromyotomy. The risk of pyloromyotomy
      for an infant who lives in a region with more than two thirds of its area
      classified as rural was 1.79 (95% confidence interval, 1.23-2.61; P<.005).
      CONCLUSIONS: The observed changes in incidence and a higher rate among male
      infants are consistent with results from previous comparative studies conducted
      in North America and Sweden. The rural/urban differences suggest that
      environmental influences related to living in these areas may have a role in the
      etiology of pyloric stenosis. Further research is needed to evaluate these
      differences.

PMID- 15939850
TI  - Intrapulmonary percussive ventilation vs incentive spirometry for children with
      neuromuscular disease.
AB  - BACKGROUND: Pulmonary infections can be life threatening for children with
      neuromuscular diseases who have impaired ability to clear secretions.
      Intrapulmonary percussive ventilation (IPV) is a pneumatic device that delivers
      air and aerosol to the lungs at frequencies of 200 to 300 cycles per minute at
      peak pressures from 20 to 40 cm H(2)O. Anecdotal reports and pilot studies show
      its safety and effectiveness in mobilizing secretions in patients with cystic
      fibrosis. OBJECTIVE: To test the hypothesis that IPV used in a pulmonary program
      for adolescents with neuromuscular disease would reduce the number of days of
      antibiotic use for pulmonary infection. METHODS: A randomized, controlled study
      was conducted to compare efficacy of IPV with incentive spirometry (IS) in
      reducing number of days of antibiotic use in adolescents with neuromuscular
      disease. The secondary endpoints were the number of respiratory infections,
      hospitalizations, and school days missed. RESULTS: A total of 18 patients were
      enrolled (9 IPV, 9 IS). Antibiotic use was significantly higher with IS (24/1000
      patient-days) compared with IPV (0/1000 patient-days), (incidence rate ratio, 43;
      95% confidence interval, 6-333). The IS group spent more days hospitalized
      (4.4/1000 patient-days vs 0/1000 patient-days) than the IPV group (incidence rate
      ratio, 8.5; 95% confidence interval, 1.1-67). The IPV group had 0 episodes of
      pneumonia or bacterial bronchitis compared with 3 events in the IS group,
      although this did not meet statistical significance. CONCLUSION: Intrapulmonary
      percussive ventilation as part of a preventive pulmonary regimen reduced days of
      antibiotic use and hospitalization for respiratory illness in adolescents with
      neuromuscular disease.

PMID- 15939851
TI  - Urgency of evaluation and outcome of acute ovarian torsion in pediatric patients.
AB  - OBJECTIVE: To describe the symptoms, diagnostic studies, and rate of ovarian
      salvage among children and adolescents with ovarian torsion. METHODS: We reviewed
      the medical records of all children with acute ovarian torsion treated at a
      university-affiliated pediatric hospital from 1987 to 2002; prenatal cases were
      excluded. For each child we recorded the time from onset of symptoms to initial
      examination and the time from initial examination to operation. We reviewed
      diagnostic tests used, operative reports, and pathology reports. RESULTS: We
      identified 22 cases; the mean age was 10.2 years (range, 3-15 years). In 6 cases
      (27%), the ovary was salvaged. Prolonged duration of symptoms prior to initial
      examination was not significantly associated with ovarian necrosis. Mean time of
      symptoms prior to care was 76 hours for both salvaged and nonsalvaged ovaries
      (range, 7-159 hours). The mean time from initial examination to operation, 11
      hours for salvaged ovaries (range, 1-23 hours) and 21 hours for nonsalvaged
      ovaries (range, 2-71 hours), was not significantly different between groups.
      Twenty-one patients underwent imaging; 19 of 20 ultrasounds and 4 of 5 computed
      tomographic scans suggested the diagnosis. Less than half (10 of 22) of the
      torsed ovaries contained cysts, teratomas, or other masses. CONCLUSIONS: These
      data suggest pediatric ovarian torsion is a more salvageable condition than
      previously reported. Prolonged time of symptoms prior to initial examination does
      not preclude ovarian salvage. Ovarian tumor accounts for less than half of cases.
      Urgent imaging and surgical management may lead to improved outcomes.

PMID- 15939852
TI  - The effect of correct and consistent condom use on chlamydial and gonococcal
      infection among urban adolescents.
AB  - OBJECTIVE: To evaluate the relationship between self-reported correct and
      consistent condom use and chlamydial and gonococcal infection. DESIGN: Cross
      sectional study. SETTING: An urban adolescent health care clinic. Patients A
      total of 509 adolescent girls tested for Chlamydia trachomatis and Neisseria
      gonorrhoeae infection by urine nucleic acid amplification tests. Main Outcome
      Measure Effect of condom use on infection rates of chlamydia and gonorrhea.
      Consistent condom use was defined as using condoms for every act of vaginal sex
      and correct use as consistent use without any of the following: beginning sex
      without a condom, taking it off before finishing sex, flipping it over, condom
      breakage, or condom slippage. RESULTS: A total of 95% of the participants were
      African American, with a mean age of 16.6 years. Chlamydia prevalence was 21%
      (105/509) and gonorrhea prevalence was 7% (36/509). Condom errors were reported
      by 316 (71%) of 442 participants who had reported using a condom at least once in
      the previous 3 months. Consistent use was reported by 176 patients (35%);
      however, both correct and consistent use was reported by only 80 patients (16%).
      After adjusting for confounders, correct and consistent use was protective for
      chlamydia (odds ratio, 0.4; 95% confidence interval, 0.2-1.0) and highly
      protective for gonorrhea (odds ratio, 0.1; 95% confidence interval, 0-0.7).
      CONCLUSION: Our findings indicate that assessing both correctness and consistency
      of use is important for evaluation of condom effectiveness.

PMID- 15939853
TI  - Milk, dairy fat, dietary calcium, and weight gain: a longitudinal study of
      adolescents.
AB  - BACKGROUND: Milk is promoted as a healthy beverage for children, but some
      researchers believe that estrone and whey protein in dairy products may cause
      weight gain. Others claim that dairy calcium promotes weight loss. OBJECTIVE: To
      assess the associations between milk, calcium from foods and beverages, dairy
      fat, and weight change over time.Design, Subjects, and Outcome Measure We
      followed a cohort of 12 829 US children, aged 9 to 14 years in 1996, who returned
      questionnaires by mail through 1999. Children annually reported their height and
      weight and completed food frequency questionnaires regarding typical past-year
      intakes. We estimated associations between annual change in body mass index (BMI)
      (calculated as weight in kilograms divided by height in meters squared) and our
      dietary factors, adjusted for adolescent growth and development, race, physical
      activity, inactivity, and (in some models) total energy intake. RESULTS: Children
      who drank more than 3 servings a day of milk gained more in BMI than those who
      drank smaller amounts (boys: beta +/- SE, 0.076 +/- 0.038 [P = .04] more than
      those who drank 1 to 2 glasses a day; girls: beta +/- SE, 0.093 +/- 0.034 [P =
      .007] more than those who drank 0 to 0.5 glass a day). For boys, milk intake was
      associated with small BMI increases during the year (beta +/- SE, 0.019 +/- 0.009
      per serving a day; P = .03); results were similar for girls (beta +/- SE, 0.015
      +/- 0.007 per serving a day; P = .04). Quantities of 1% milk (boys) and skim milk
      (girls) were significantly associated with BMI gain, as was total dietary calcium
      intake. Multivariate analyses of milk, dairy fat, calcium, and total energy
      intake suggested that energy was the most important predictor of weight gain.
      Analyses of year-to-year changes in milk, calcium, dairy fat, and total energy
      intakes provided generally similar conclusions; an increase in energy intake from
      the prior year predicted BMI gain in boys (P = .003) and girls (P = .03).
      CONCLUSIONS: Children who drank the most milk gained more weight, but the added
      calories appeared responsible. Contrary to our hypotheses, dietary calcium and
      skim and 1% milk were associated with weight gain, but dairy fat was not.
      Drinking large amounts of milk may provide excess energy to some children.

PMID- 15939854
TI  - Subsidized housing and children's nutritional status: data from a multisite
      surveillance study.
AB  - BACKGROUND: A critical shortage of affordable housing for low-income families
      continues in the United States. Children in households that are food insecure are
      at high risk for adverse nutritional and health outcomes and thus may be more
      vulnerable to the economic pressures exerted by high housing costs. Only about
      one fourth of eligible families receive a federally financed housing subsidy. Few
      studies have examined the effects of such housing subsidies on the health and
      nutritional status of low-income children. OBJECTIVE: To examine the relationship
      between receiving housing subsidies and nutritional and health status among young
      children in low-income families, especially those that are food insecure. DESIGN:
      Cross-sectional observational study. SETTING AND PARTICIPANTS: From August 1998
      to June 2003, the Children's Sentinel Nutrition Assessment Program interviewed
      caregivers of children younger than 3 years in pediatric clinics and emergency
      departments in 6 sites (Arkansas, California, Maryland, Massachusetts, Minnesota,
      and Washington, DC). Interviews included demographics, perceived child health,
      the US Household Food Security Scale, and public assistance program
      participation. Children's weight at the time of the visit was documented. The
      study sample consisted of all renter households identified as low income by their
      participation in at least 1 means-tested program. MAIN OUTCOME MEASURES: Weight
      for age, self-reported child health status, and history of hospitalization.
      RESULTS: Data were available for 11 723 low-income renter families; 27% were
      receiving a public housing subsidy, and 24% were food insecure. In multivariable
      analyses, stratified by household food security status and adjusted for potential
      confounding variables, children of food-insecure families not receiving housing
      subsidies had lower weight for age (adjusted mean z score, -0.025 vs 0.205;
      P<.001) compared with children of food-insecure families receiving housing
      subsidies. Compared with children in food-insecure, subsidized families, the
      adjusted odds ratio (95% confidence interval) for weight-for-age z score more
      than 2 SDs below the mean was 2.11 (1.34-3.32) for children in food-insecure,
      nonsubsidized families. CONCLUSIONS: In a large convenience sentinel sample, the
      children of low-income renter families who receive public housing subsidies are
      less likely to have anthropometric indications of undernutrition than those of
      comparable families not receiving housing subsidies, especially if the family is
      not only low income but also food insecure.

PMID- 15939855
TI  - Unit-dose packaging of iron supplements and reduction of iron poisoning in young
      children.
AB  - BACKGROUND: Iron poisoning is a major cause of unintentional poisoning death in
      young children. The US Food and Drug Administration proclaimed a regulation for
      unit-dose packaging of iron supplements in 1997. OBJECTIVE: To determine whether
      the requirement for unit-dose packaging of iron supplements decreases the
      incidence of iron ingestion and the incidence of deaths due to iron poisoning in
      children younger than 6 years. METHODS: This is a preintervention
      postintervention study of the US federally mandated requirement for unit-dose
      packaging of iron supplements. The 10 years prior to the intervention were
      compared with the 5 years after its promulgation. The incidences of iron
      ingestion and of iron poisoning deaths for children younger than 6 years were
      obtained from the annual reports of the American Association of Poison Control
      Centers (Washington, DC). RESULTS: The average number of iron ingestion calls per
      1000 of all calls to poison control centers regarding children younger than 6
      years decreased from 2.99 per 1000 to 1.91 per 1000 (odds ratio, 1.29 [95%
      confidence interval, 1.27-1.32]; P<.001). The number of deaths decreased from 29
      to 1 (odds ratio, 13.56 [95% confidence interval, 1.85-99.52]; P = .03).
      CONCLUSIONS: These are the first data that show a decrease in the incidence of
      nonintentional ingestion of a specific drug by young children and a decrease in
      mortality from poisoning by this drug after the introduction of unit-dose
      packaging. There was a decrease in the incidence of iron ingestion and a dramatic
      decrease in the number of deaths due to iron poisoning. This validates unit-dose
      packaging as an effective strategy for the prevention of iron poisoning and iron
      poisoning deaths in young children. This highly effective intervention should be
      considered for other medications with a high hazard for morbidity and mortality
      when taken as an overdose.

PMID- 15939856
TI  - Continuing medical education in child sexual abuse: cognitive gains but not
      expertise.
AB  - OBJECTIVE: Describe the effect of an educational intervention on medical provider
      knowledge and competency regarding child sexual abuse. DESIGN: Using a before and
      after trial design with an educational intervention, the study assesses knowledge
      changes in specific content areas and describes a post-intervention competency
      assessment. SETTING/ PARTICIPANTS: Voluntary participation of practicing medical
      providers and pediatric residents. Intervention Completion of a self-study, case
      based, published learning curriculum on child sexual abuse, including a work book
      and videotaped genital examinations. MAIN OUTCOME MEASURES: Pre- and post
      intervention multiple choice and short answer (30 questions) test results as well
      as a written response to a clinical case scenario. RESULTS: Sixty-four
      participants completed pre- and post-tests. The average posttest score (26.9/30,
      SD = 4.13) was significantly higher (P< .001) than the average pretest score
      (20.4/30, SD = 1.65). More than half (59.4%) of providers did not correctly
      interpret the exam findings, 28.1% did not correctly reassure the child and
      family, and 39.1% did not indicate an appropriate understanding of the legal
      implications. CONCLUSIONS: Motivated medical providers demonstrated significant
      knowledge gains regarding the evaluation of child sexual abuse following
      participation in the educational program. This new knowledge was not enough to
      provide competency in the interpretation of genital findings or in offering legal
      advocacy to the families. Competence in these areas may in fact represent the
      domain of experts, not primary care providers, and further studies are needed to
      determine how much experience is necessary to provide competency in these areas.

PMID- 15939857
TI  - Weight gain since infancy and prepubertal body dissatisfaction.
AB  - OBJECTIVE: To investigate whether body dissatisfaction at prepuberty is
      associated with preceding changes in relative weight since infancy. DESIGN: A
      longitudinal cohort study. Follow-up of weight and height from age 7 months to 8
      years; evaluation of body dissatisfaction at age 8 years. SETTING AND
      PARTICIPANTS: The subjects were 205 girls and 230 boys participating in a
      prospective randomized atherosclerosis prevention trial in Finland. MAIN OUTCOME
      MEASURES: A pictorial instrument was used in measuring estimated current and
      desired body sizes. A difference between the 2 indicated body dissatisfaction.
      RESULTS: Children, particularly girls, who wished to be thinner at age 8 years
      had, on average, a more rapid increase in relative weight between ages 3 and 8
      years compared with other children. Slopes of the average trends of change in
      weight differed significantly between the children wishing to be thinner, those
      who were satisfied with their size, and those who wished to look heavier (P =
      .002 in girls; P = .02 in boys). CONCLUSION: Body dissatisfaction at prepuberty
      may reflect changes in weight during the preceding several years.

PMID- 15939858
TI  - Continuity of methylphenidate treatment for attention-deficit/hyperactivity
      disorder.
AB  - OBJECTIVE: To compare the continuity of methylphenidate hydrochloride (MPH)
      therapy among youth Medicaid beneficiaries treated for attention
      deficit/hyperactivity disorder with immediate-release (IR) or extended-release
      (ER) MPH formulations. Method An analysis was conducted of statewide California
      Medicaid claims (2000-2003) focusing on children and adolescents, ages 6 to 17
      years, who started ER-MPH or IR-MPH treatment for attention-deficit/hyperactivity
      disorder. The study cohorts were limited to youth who had not filled a
      prescription for MPHs, amphetamines, pemoline, or atomoxetine for 6 months
      preceding the index prescription and remained eligible for Medicaid benefits for
      the following 12 months. The study groups were compared with respect to
      background demographic traits and clinical characteristics. Mean and median
      duration of MPH treatment episodes were defined to terminate if a gap of 30 or
      more days occurred from the end of the last prescription supply to the start of
      the next prescription. Survival time ratios were used to assess treatment
      duration controlling for group differences in background characteristics.
      RESULTS: As compared with patients initiating IR-MPH treatment, patients
      initiating ER-MPH treatment had a significantly longer mean estimated duration of
      treatment (ER-MPH, 140.3 days [95% confidence interval (CI), 136.3-144.4 days] vs
      IR-MPH, 103.4 days [95% CI, 101.3-103.4 days]). Similar results were found in
      analyses stratified by patient age, race/ethnicity, and sex. Controlling for
      group differences in age, sex, race/ethnicity, coprescribed psychotropic
      medications, other treated mental disorders, case management, managed care
      participation, and seasonal effects, ER-MPH treatment initiation was associated
      with an average 37% longer duration of treatment than IR-MPH treatment (survival
      time ratio, 1.37 [95% CI, 1.32-1.42]). Among patients treated with ER-MPH,
      treatment initiation with an osmotic release oral system MPH (Concerta) was
      associated with significantly longer mean duration (147.2 days [95% CI, 142.6
      151.7 days]) than treatment initiation with Metadate CD (controlled delivery)
      (113.0 days [95% CI, 100.9-125.1 days]) or Ritalin LA (long acting) (101.1 days
      [95% CI, 91.2-111.0 days]), respectively. CONCLUSIONS: Extended-release MPH
      formulations were associated with greater continuity of MPH treatment than IR
      formulations in the study population. Initial selection of an ER formulation may
      help to prolong continuity of MPH therapy among youth Medicaid beneficiaries with
      attention-deficit/hyperactivity disorder.

PMID- 15939859
TI  - Effects of a large-scale industrial disaster on rates of symptoms consistent with
      posttraumatic stress disorders among schoolchildren in toulouse.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) has been studied largely among
      adults and in the context of intentional, collective experiences such as war and
      terrorism. Far less is known about PTSD among adolescents and resulting from
      massive industrial accidents. Such an accident in Toulouse, France, 10 days after
      the World Trade Center disaster, provided an opportunity to examine its effects
      among adolescents already sensitized by media coverage of the World Trade Center
      disaster. OBJECTIVES: (1) To assess the presence of symptoms consistent with PTSD
      (SCW-PTSD) among adolescents in Toulouse after a massive industrial accident, (2)
      to determine the "excess" of SCW-PTSD among those directly exposed vs those
      nondirectly exposed, and (3) to examine dosage effects for exposure and the
      cumulative effect on PTSD of accident-related experiences. DESIGN, SETTING, AND
      PARTICIPANTS: A survey containing questions on exposure and SCW-PTSD was
      administered to students aged 11 years, 13 years, 15 years, and 17 years who were
      enrolled in randomly selected, grade-stratified classrooms from schools for
      directly exposed students (n = 577) in Toulouse and nondirectly exposed students
      (n = 900) in the region.Main Outcome Measure The prevalence of SCW-PTSD among
      directly exposed and nondirectly exposed students. RESULTS: Nine months after the
      industrial accident, 44.6% of 11- and 13-year-old directly exposed students and
      28.5% of 15- and 17-year-old directly exposed students still showed SCW-PTSD,
      compared with 22.1% of 11- and 13-year-old nondirectly exposed students and 4.4%
      of 15-year-old nondirectly exposed students. Among 11- and 13-year-olds, the
      likelihood of having SCW-PTSD was higher for girls who were enrolled in
      elementary schools, were personally injured, and had severe damage at home, as
      opposed to boys who were high-school students without severe damage at home or
      personal injury. Among the 15- and 17-year-olds, being a girl, 17 years old, and
      personally injured increased the likelihood of having SCW-PTSD, as opposed to 15
      year-old boys who were not injured. The effects of injuries were cumulative:
      students injured personally and with an injured family member were more likely to
      have SCW-PTSD than those experiencing either personal or family injury but not
      both. Excess of SCW-PTSD attributable to direct exposure was 50.5% for 11-year
      olds, 49.3% for 13-year-olds, and 73.5% for 15-year-olds. CONCLUSIONS: A
      substantial proportion of Toulouse adolescents still had SCW-PTSD 9 months after
      the accident. Directly exposed students were far more likely to show SCW-PTSD
      than those nondirectly exposed, but both groups had SCW-PTSD at rates that were
      higher than expected. The symptoms were associated with demographic
      characteristics and direct experiences of trauma. Higher rates applied to
      students who were personally injured with injured family members and severe
      damage at home. Students with these characteristics predictive of SCW-PTSD should
      be given prompt attention to avoid long-lasting effects.

PMID- 15939860
TI  - The "lost boys of Sudan": functional and behavioral health of unaccompanied
      refugee minors re-settled in the United States.
AB  - OBJECTIVE: To assess the functional and behavioral health of unaccompanied
      Sudanese refugee minors approximately 1 year after resettlement in the United
      States. DESIGN: A descriptive survey. SETTING: Local refugee foster care programs
      affiliated with the US Unaccompanied Refugee Minors Program. PARTICIPANTS: A
      total of 304 Sudanese refugee minors enrolled in the US Unaccompanied Refugee
      Minors Program. MAIN OUTCOME MEASURES: Health outcomes were assessed using the
      Harvard Trauma Questionnaire and the Child Health Questionnaire. Outcomes
      included the diagnosis of posttraumatic stress disorder and scores on all Child
      Health Questionnaire subscales and global single-item assessments. RESULTS:
      Twenty percent of the minors had a diagnosis of posttraumatic stress disorder and
      were more likely to have lower (worse) scores on all the Child Health
      Questionnaire subscales. Low functional and behavioral health scores were seen
      mainly in functioning in the home and in subjective health ratings. Social
      isolation and history of personal injury were associated with posttraumatic
      stress disorder. CONCLUSIONS: Unaccompanied Sudanese minors have done well in
      general. The minors function well in school and in activities; however,
      behavioral and emotional problems manifest in their home lives and emotional
      states. The subset of children with traumatic symptoms had characteristics that
      may distinguish them from their peers and that may inform future resettlement
      services for unaccompanied minors in the United States.

PMID- 15939861
TI  - When perception is reality.

PMID- 15939862
TI  - Progress in the prevention of childhood iron poisoning.

PMID- 15939864
TI  - Impact of mass communication in the implementation of influenza vaccination for
      infants.

PMID- 15939865
TI  - The effect of supplemental fluids or feedings during the first days of life on
      the success and duration of breastfeeding: a systematic review of randomized
      controlled trials.

PMID- 15939866
TI  - Coinfection with hepatitis C virus and human immunodeficiency virus 1 in
      children: pathogenesis and screening.

PMID- 15939867
TI  - An essential role for an inositol polyphosphate multikinase, Ipk2, in mouse
      embryogenesis and second messenger production.
AB  - Phospholipase C and several inositol polyphosphate kinase (IPK) activities
      generate a branched ensemble of inositol polyphosphate second messengers that
      regulate cellular signaling pathways in the nucleus and cytoplasm. Here, we
      report that mice deficient for Ipk2 (also known as inositol polyphosphate
      multikinase), an inositol trisphosphate and tetrakisphosphate 6/5/3-kinase active
      at several places in the inositol metabolic pathways, die around embryonic day
      9.5 with multiple morphological defects, including abnormal folding of the neural
      tube. Metabolic analysis of Ipk2-deficient cells demonstrates that synthesis of
      the majority of inositol pentakisphosphate, hexakisphosphate and pyrophosphate
      species are disrupted, although the presence of 10% residual inositol
      hexakisphosphate indicates the existence of a minor alternative pathway. Agonist
      induced inositol tris- and bis-phosphate production and calcium release responses
      are present in homozygous mutant cells, indicating that the observed mouse
      phenotypes are a result of failure to produce higher inositol polyphosphates. Our
      data demonstrate that Ipk2 plays a major role in the synthesis of inositol
      polyphosphate messengers derived from inositol 1,4,5-trisphosphate and uncovers a
      role for their production in embryogenesis and normal development.

PMID- 15939868
TI  - Disruption of the mouse inositol 1,3,4,5,6-pentakisphosphate 2-kinase gene,
      associated lethality, and tissue distribution of 2-kinase expression.
AB  - Many functions have been suggested for inositol 1,2,3,4,5,6-hexakisphosphate
      (InsP6), including mRNA export, nonhomologous end-joining, endocytosis, and ion
      channel regulation. However, it remains to be demonstrated that InsP6 is
      necessary for in vivo survival. We previously isolated a cDNA encoding the
      mammalian inositol 1,3,4,5,6-pentakisphosphate (InsP5) 2-kinase (2-kinase), the
      enzyme that converts InsP5 to InsP6. We used the sequence to search the
      BayGenomics databases and identify an ES cell line (XA232) that has a gene trap
      construct embedded in the 2-kinase gene. We obtained a mouse from this line,
      produced heterozygotes, and confirmed that the heterozygotes contain the trapping
      construct and have diminished 2-kinase activity. Breeding the XA232 heterozygotes
      produced no homozygous offspring; thus, loss of 2-kinase is lethal in mice.
      Dissections of embryonic day-8.5 uteri yielded no homozygous embryos; thus, the
      mice die before day 8.5 postcoitum. The gene trap construct contains a beta
      galactosidase/neomycin reporter gene, allowing us to stain heterozygotes for beta
      galactosidase to determine tissue-specific expression of 2-kinase protein. 2
      kinase is expressed in the hippocampus, the cortex, the Purkinje layer of the
      cerebellum in the brain, in cardiomyocytes, and in the testes of adult mice. At
      day 9.5 postcoitum, 2-kinase was expressed in the notochord, the ventricular
      layer of the neural tube, and the myotome of the somites. Intense staining was
      also seen in the yolk sac, suggesting that InsP6 is necessary for yolk sac
      development or function. Furthermore, failure of yolk sac development or function
      is consistent with the early lethality of 2-kinase embryos.

PMID- 15939869
TI  - Robust hepatitis C virus infection in vitro.
AB  - The absence of a robust cell culture model of hepatitis C virus (HCV) infection
      has severely limited analysis of the HCV life cycle and the development of
      effective antivirals and vaccines. Here we report the establishment of a simple
      yet robust HCV cell culture infection system based on the HCV JFH-1 molecular
      clone and Huh-7-derived cell lines that allows the production of virus that can
      be efficiently propagated in tissue culture. This system provides a powerful tool
      for the analysis of host-virus interactions that should facilitate the discovery
      of antiviral drugs and vaccines for this important human pathogen.

PMID- 15939870
TI  - A general method for greatly improving the affinity of antibodies by using
      combinatorial libraries.
AB  - Look-through mutagenesis (LTM) is a multidimensional mutagenesis method that
      simultaneously assesses and optimizes combinatorial mutations of selected amino
      acids. The process focuses on a precise distribution within one or more
      complementarity determining region (CDR) domains and explores the synergistic
      contribution of amino acid side-chain chemistry. LTM was applied to an anti-TNF
      alpha antibody, D2E7, which is a challenging test case, because D2E7 was highly
      optimized (K(d) = 1 nM) by others. We selected and incorporated nine amino acids,
      representative of the major chemical functionalities, individually at every
      position in each CDR and across all six CDRs (57 aa). Synthetic oligonucleotides,
      each introducing one amino acid mutation throughout the six CDRs, were pooled to
      generate segregated libraries containing single mutations in one, two, and/or
      three CDRs for each V(H) and V(L) domain. Corresponding antibody libraries were
      displayed on the cell surface of yeast. After positive binding selection, 38
      substitutions in 21 CDR positions were identified that resulted in higher
      affinity binding to TNF-alpha. These beneficial mutations in both V(H) and V(L)
      were represented in two combinatorial beneficial mutagenesis libraries and
      selected by FACS to produce a convergence of variants that exhibit between 500-
      and 870-fold higher affinities. Importantly, these enhanced affinities translate
      to a 15- to 30-fold improvement in in vitro TNF-alpha neutralization in an L929
      bioassay. Thus, this LTM/combinatorial beneficial mutagenesis strategy generates
      a comprehensive energetic map of the antibody-binding site in a facile and rapid
      manner and should be broadly applicable to the affinity maturation of antibodies
      and other proteins.

PMID- 15939871
TI  - Reading depends on writing, in Chinese.
AB  - Language development entails four fundamental and interactive abilities:
      listening, speaking, reading, and writing. Over the past four decades, a large
      body of evidence has indicated that reading acquisition is strongly associated
      with a child's listening skills, particularly the child's sensitivity to
      phonological structures of spoken language. Furthermore, it has been hypothesized
      that the close relationship between reading and listening is manifested
      universally across languages and that behavioral remediation using strategies
      addressing phonological awareness alleviates reading difficulties in dyslexics.
      The prevailing view of the central role of phonological awareness in reading
      development is largely based on studies using Western (alphabetic) languages,
      which are based on phonology. The Chinese language provides a unique medium for
      testing this notion, because logographic characters in Chinese are based on
      meaning rather than phonology. Here we show that the ability to read Chinese is
      strongly related to a child's writing skills and that the relationship between
      phonological awareness and Chinese reading is much weaker than that in reports
      regarding alphabetic languages. We propose that the role of logograph writing in
      reading development is mediated by two possibly interacting mechanisms. The first
      is orthographic awareness, which facilitates the development of coherent,
      effective links among visual symbols, phonology, and semantics; the second
      involves the establishment of motor programs that lead to the formation of long
      term motor memories of Chinese characters. These findings yield a unique insight
      into how cognitive systems responsible for reading development and reading
      disability interact, and they challenge the prominent phonological awareness
      view.

PMID- 15939872
TI  - Uterine sensing of the embryo.

PMID- 15939873
TI  - Historical influences on community ecology.

PMID- 15939874
TI  - Gene expression patterns define key transcriptional events in cell-cycle
      regulation by cAMP and protein kinase A.
AB  - Although a substantial number of hormones and drugs increase cellular cAMP
      levels, the global impact of cAMP and its major effector mechanism, protein
      kinase A (PKA), on gene expression is not known. Here we show that treatment of
      murine wild-type S49 lymphoma cells for 24 h with 8-(4-chlorophenylthio)-cAMP (8
      CPT-cAMP), a PKA-selective cAMP analog, alters the expression of approximately
      4,500 of approximately 13,600 unique genes. By contrast, gene expression was
      unaltered in Kin- S49 cells (that lack PKA) incubated with 8-CPT-cAMP. Changes in
      mRNA and protein expression of several cell-cycle regulators accompanied cAMP
      induced G1-phase cell-cycle arrest of wild-type S49 cells. Within 2 h, 8-CPT-cAMP
      altered expression of 152 genes that contain evolutionarily conserved cAMP
      response elements within 5 kb of transcriptional start sites, including the
      circadian clock gene Per1. Thus, cAMP through its activation of PKA produces
      extensive transcriptional regulation in eukaryotic cells. These transcriptional
      networks include a primary group of cAMP-response element-containing genes and
      secondary networks that include the circadian clock.

PMID- 15939875
TI  - Bird genes give new insights into the origins of lipid antigen presentation.

PMID- 15939876
TI  - Detection of glutamate release from neurons by genetically encoded surface
      displayed FRET nanosensors.
AB  - Glutamate is the predominant excitatory neurotransmitter in the mammalian brain.
      Once released, its rapid removal from the synaptic cleft is critical for
      preventing excitotoxicity and spillover to neighboring synapses. Despite
      consensus on the role of glutamate in normal and disease physiology, technical
      issues limit our understanding of its metabolism in intact cells. To monitor
      glutamate levels inside and at the surface of living cells, genetically encoded
      nanosensors were developed. The fluorescent indicator protein for glutamate
      (FLIPE) consists of the glutamate/aspartate binding protein ybeJ from Escherichia
      coli fused to two variants of the green fluorescent protein. Three sensors with
      lower affinities for glutamate were created by mutation of residues peristeric to
      the ybeJ binding pocket. In the presence of ligands, FLIPEs show a concentration
      dependent decrease in FRET efficiency. When expressed on the surface of rat
      hippocampal neurons or PC12 cells, the sensors respond to extracellular glutamate
      with a reversible concentration-dependent decrease in FRET efficiency.
      Depolarization of neurons leads to a reduction in FRET efficiency corresponding
      to 300 nM glutamate at the cell surface. No change in FRET was observed when
      cells expressing sensors in the cytosol were superfused with up to 20 mM
      glutamate, consistent with a minimal contribution of glutamate uptake to
      cytosolic glutamate levels. The results demonstrate that FLIPE sensors can be
      used for real-time monitoring of glutamate metabolism in living cells, in
      tissues, or in intact organisms, providing tools for studying metabolism or for
      drug discovery.

PMID- 15939877
TI  - Engineered single-chain dimeric streptavidins with an unexpected strong
      preference for biotin-4-fluorescein.
AB  - Streptavidin, a homotetrameric protein with extremely tight biotin binding (K(d)
      < or = 10(-14) M), has been widely used as an affinity reagent. Its utility would
      be increased by engineering single-chain mutants with a wide spectrum of
      affinities, more suitable for phage-display and chip technologies. By a circular
      permutation procedure, we converted streptavidin to a single-chain dimer (SCD)
      with two biotin-binding sites and introduced random mutations by error-prone PCR.
      Clones from a phagemid library, expressed as gene-3 fusion proteins on M13
      bacteriophage, were panned with biotinylated beads, and SCD genes from affinity
      enriched phage were subcloned to produce soluble proteins. Purification of
      products from the original gene and two mutants by FPLC and analysis by MALDI-TOF
      MS showed they exist in both dimeric (single-chain) and tetrameric (two-chain)
      forms, which were further characterized for their binding affinity to biotin-4
      fluorescein (B4F) by fluorescence polarization and intensity measurements. K'(d)
      values for B4F ranged from approximately 10(-11) to 10(-10) M, although K(d)
      values for biotin ranged from 10(-6) to 10(-5) M. These results point to the
      possibility of combining an SCD streptavidin mutant with B4F derivatives to
      create a fluorescence-tagged affinity system with tight but still-reversible
      interaction that could be used sequentially with ordinary streptavidin-biotin for
      composite separation or analysis steps.

PMID- 15939878
TI  - Gene transfer to human joints: progress toward a gene therapy of arthritis.
AB  - This article describes the clinical application of gene therapy to a nonlethal
      disease, rheumatoid arthritis (RA). Intraarticular transfer of IL-1 receptor
      antagonist (IL-1Ra) cDNA reduces disease in animal models of RA. Whether this
      procedure is safe and feasible in humans was addressed in a phase I clinical
      study involving nine postmenopausal women with advanced RA who required
      unilateral sialastic implant arthroplasty of the 2nd-5th metacarpophalangeal
      (MCP) joints. Cultures of autologous synovial fibroblasts were established and
      divided into two. One was transduced with a retrovirus carrying IL-1Ra cDNA; the
      other provided untransduced, control cells. In a dose escalation, double-blinded
      fashion, two MCP joints were injected with transduced cells, and two MCP joints
      received control cells. One week later, injected joints were resected and
      examined for evidence of successful gene transfer and expression by using RT-PCR,
      ex vivo production of IL-1Ra, in situ hybridization, and immunohistochemistry.
      All subjects tolerated the protocol well, without adverse events. Unlike control
      joints, those receiving transduced cells gave positive RT-PCR signals. Synovia
      that were recovered from the MCP joints of intermediate and high dose subjects
      produced elevated amounts of IL-1Ra (P = 0.01). Clusters of cells expressing high
      levels of IL-1Ra were present on synovia of transduced joints. No adverse events
      occurred. Thus, it is possible to transfer a potentially therapeutic gene safely
      to human rheumatoid joints and to obtain intraarticular, transgene expression.
      This conclusion justifies additional efficacy studies and encourages further
      development of genetic approaches to the treatment of arthritis and related
      disorders.

PMID- 15939879
TI  - Virulent Coxiella burnetii does not activate human dendritic cells: role of
      lipopolysaccharide as a shielding molecule.
AB  - Coxiella burnetii is an obligate intracellular bacterium and the etiological
      agent of the zoonotic disease Q fever. Acute human Q fever is characterized by
      flu-like symptoms that, in some cases, can result in a persistent infection that
      may reactivate months or years after initial exposure. Mechanisms by which this
      obligate parasite evades clearance by the host immune response during persistent
      infection are unknown. Here, we characterized the interaction of C. burnetii with
      dendritic cells (DC), critical components of both innate and adaptive immunity.
      Human DC were infected with two isogenic C. burnetii strains that differ in LPS
      length. Infection by the Nine Mile phase I (NMI) strain, which is fully virulent
      and produces full-length LPS, did not result in DC maturation. In contrast,
      infection by the avirulent Nine Mile phase II strain, producing a severely
      truncated LPS, resulted in toll-like receptor 4-independent DC maturation and
      approximately 10-fold more IL-12 and TNF production. NMI did not actively inhibit
      DC maturation as NMI-infected DC subsequently matured if treated with Escherichia
      coli LPS or Nine Mile phase II. Furthermore, removal of LPS from NMI dramatically
      increased its ability to stimulate DC. We propose a model whereby LPS of virulent
      C. burnetii masks toll-like receptor ligands from innate immune recognition by
      DC, thereby allowing replication without significant maturation or inflammatory
      cytokine production. This immune evasion strategy may allow C. burnetii to
      persist in an immunocompetent host.

PMID- 15939880
TI  - Different mutation signatures in DNA polymerase eta- and MSH6-deficient mice
      suggest separate roles in antibody diversification.
AB  - Hypermutation in immunoglobulin genes produces a high frequency of substitutions
      of all four bases, which are likely generated by low-fidelity DNA polymerases.
      Indeed, humans deficient for DNA polymerase (pol) eta have decreased
      substitutions of A.T base pairs in variable and switch regions. To study the role
      of pol eta in a genetically tractable system, we created mice lacking pol eta. B
      cells from Polh-/- mice produced normal amounts of IgG, indicating that pol eta
      does not affect class switch recombination. Similar to their human counterparts,
      variable and switch regions from Polh-/- mice had fewer substitutions of A.T base
      pairs and correspondingly more mutations of C.G base pairs, which firmly
      establishes a central role for pol eta in hypermutation. Notably, the location
      and types of substitutions differ markedly from those in Msh6-/- clones, which
      also have fewer A.T mutations. The data suggest that pol eta preferentially
      synthesizes a repair patch on the nontranscribed strand, whereas MSH6 functions
      to generate the patch.

PMID- 15939881
TI  - UV irradiation stimulates histone acetylation and chromatin remodeling at a
      repressed yeast locus.
AB  - Chromatin immunoprecipitation with anti-acetyl histone H3 (K9 and K14) and anti
      acetyl histone H4 (K5, K8, K12, and K16) antibodies shows that Lys-9 and/or Lys
      14 of histone H3, but not the relevant sites of histone H4 in nucleosomes at the
      repressed MFA2 promoter, are hyperacetylated after UV irradiation. This level of
      histone hyperacetylation diminishes gradually as repair proceeds. Accompanying
      this, chromatin in the promoter becomes more accessible to restriction enzymes
      after UV irradiation and returns to the pre-UV state gradually. UV-related
      histone hyperacetylation and chromatin remodeling in the MFA2 promoter depend on
      Gcn5p and partially on Swi2p, respectively. Deletion of GCN5, but not of SWI2,
      impairs repair of DNA damage in the MFA2 promoter. The post-UV histone
      modifications and chromatin remodeling at the repressed MFA2 promoter do not
      activate MFA2 transcriptionally, nor do they require damage recognition by Rad4p
      or Rad14p. Furthermore, we show that UV irradiation triggers genome-wide histone
      hyperacetylation at both histone H3 and H4. These experiments indicate that
      chromatin at a yeast repressed locus undergoes active change after UV radiation
      treatment and that failure to achieve histone H3 hyperacetylation impairs the
      repair of DNA damage.

PMID- 15939882
TI  - Actin polymerization kinetics, cap structure, and fluctuations.
AB  - Polymerization of actin proteins into dynamic structures is essential to
      eukaryotic cell life, motivating many in vitro experiments measuring
      polymerization kinetics of individual filaments. Here, we model these kinetics,
      accounting for all relevant steps revealed by experiment: polymerization,
      depolymerization, random ATP hydrolysis, and release of phosphate (P(i)). We
      relate filament growth rates to the dynamics of ATP-actin and ADP-P(i)-actin caps
      that develop at filament ends. At the critical concentration of the barbed end,
      c(crit), we find a short ATP cap and a long fluctuation-stabilized ADP-P(i) cap.
      We show that growth rates and the critical concentration at the barbed end are
      intimately related to cap structure and dynamics. Fluctuations in filament
      lengths are described by the length diffusion coefficient, D. Recently Fujiwara
      et al. [Fujiwara, I., Takahashi, S., Takaduma, H., Funatsu, T. & Ishiwata, S.
      (2002) Nat. Cell Biol. 4, 666-673] and Kuhn and Pollard [Kuhn, J. & Pollard, T.
      D. (2005) Biophys. J. 88, 1387-1402] observed large length fluctuations slightly
      above c(crit), provoking speculation that growth may proceed by oligomeric rather
      than monomeric on-off events. For the single-monomer growth process, we find that
      D exhibits a pronounced peak below c(crit), due to filaments alternating between
      capped and uncapped states, a mild version of the dynamic instability of
      microtubules. Fluctuations just above c(crit) are enhanced but much smaller than
      those reported experimentally. Future measurements of D as a function of
      concentration can help identify the origin of the observed fluctuations.

PMID- 15939883
TI  - Variation in DISC1 affects hippocampal structure and function and increases risk
      for schizophrenia.
AB  - Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene
      expressed predominantly within the hippocampus. We typed 12 single-nucleotide
      polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype
      [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was
      associated with schizophrenia in a family-based sample (P = 0.002). A common
      nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated
      with schizophrenia (P = 0.004). Based on primary expression of DISC1 in
      hippocampus, we hypothesized that allelic variation at Ser704Cys would have a
      measurable impact on hippocampal structure and function as assayed via specific
      hippocampus-related intermediate phenotypes. In addition to overtransmission in
      schizophrenia, the Ser allele was associated with altered hippocampal structure
      and function in healthy subjects, including reduced hippocampal gray matter
      volume and altered engagement of the hippocampus during several cognitive tasks
      assayed with functional magnetic resonance imaging. These convergent data suggest
      that allelic variation within DISC1, either at Ser704Cys or haplotypes monitored
      by it, increases the risk for schizophrenia and that the mechanism of this effect
      involves structural and functional alterations in the hippocampal formation.

PMID- 15939884
TI  - Characterization of two avian MHC-like genes reveals an ancient origin of the CD1
      family.
AB  - Many of the genes that comprise the vertebrate adaptive immune system are
      conserved across wide evolutionary time scales. Most notably, homologs of the
      mammalian MHC gene family have been found in virtually all jawed vertebrates,
      including sharks, bony fishes, reptiles, and birds. The CD1 family of antigen
      presenting molecules are related to the MHC class I family but have evolved to
      bind and present lipid antigens to T cells. Here, we describe two highly
      divergent nonclassical MHC class I genes found in the chicken (Gallus gallus)
      that have sequence homology to the mammalian CD1 family of proteins. One of the
      chicken CD1 genes expresses a full-length transcript, whereas the other has
      multiple splice variants. Both Southern blot and single nucleotide polymorphism
      analysis indicates that chicken CD1 is relatively nonpolymorphic. Moreover, cross
      hybridizing bands are present in other bird species, suggesting broad
      conservation in the avian class. Northern analysis of chicken tissue shows a high
      level of CD1 expression in the bursa and spleen. In addition, molecular modeling
      predicts that the potential antigen-binding pocket is probably hydrophobic, a
      universal characteristic of CD1 molecules. Genomic analysis indicates that the
      CD1 genes are located on chicken chromosome 16 and maps to within 200 kb of the
      chicken MHC B locus, suggesting that CD1 genes diverged from classical MHC genes
      while still linked to the major histocompatibility complex locus. The existence
      of CD1 genes in an avian species suggests that the origin of CD1 extends deep
      into the evolutionary history of terrestrial vertebrates.

PMID- 15939885
TI  - Selective modification of alternative splicing by indole derivatives that target
      serine-arginine-rich protein splicing factors.
AB  - The prevalence of alternative splicing as a target for alterations leading to
      human genetic disorders makes it highly relevant for therapy. Here we have used
      in vitro splicing reactions with different splicing reporter constructs to screen
      4,000 chemical compounds for their ability to selectively inhibit spliceosome
      assembly and splicing. We discovered indole derivatives as potent inhibitors of
      the splicing reaction. Importantly, compounds of this family specifically inhibit
      exonic splicing enhancer (ESE)-dependent splicing, because they interact directly
      and selectively with members of the serine-arginine-rich protein family.
      Treatment of cells expressing reporter constructs with ESE sequences demonstrated
      that selected indole derivatives mediate inhibition of ESE usage in vivo and
      prevent early splicing events required for HIV replication. This discovery opens
      the exciting possibility of a causal pharmacological treatment of aberrant
      splicing in human genetic disorders and development of new antiviral therapeutic
      approaches.

PMID- 15939886
TI  - Nitric oxide synthase II suppresses the growth and metastasis of human cancer
      regardless of its up-regulation of protumor factors.
AB  - Inducible nitric oxide (NO) synthase (NOS) II has been implicated in macrophage
      mediated antitumor activity. However, use of the NOS II gene in cancer therapy is
      problematic because of the double-edged nature of NO action. Herein we show that
      adenoviral vectors mediated effective NOS II gene transfer into various human
      tumors. Production of NO significantly up-regulated multiple angiogenic
      molecules. However, the NO-producing tumor cells did not form tumors or
      metastases in ectopic or orthotopic xenograft nude mouse models. The dramatic
      loss of malignancy was due to NO-mediated apoptosis. We also generated a series
      of adenoviral vectors harboring mutant NOS II genes that expressed mutant NOS II
      proteins with defined levels of enzymatic activity. Tumor cells transduced with
      these NOS II genes produced NO at different levels, which directly correlated
      with the antitumor activity in vitro and in vivo. This demonstration using a
      relevant biological system shows that NO produces dose-dependent antitumor
      activity in vitro and in vivo, regardless of its up-regulation of protumor
      factors.

PMID- 15939887
TI  - Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and
      likely to have been present in the primordial MHC.
AB  - CD1 molecules play an important role in the immune system, presenting lipid
      containing antigens to T and NKT cells. CD1 genes have long been thought to be as
      ancient as MHC class I and II genes, based on various arguments, but thus far
      they have been described only in mammals. Here we describe two CD1 genes in
      chickens, demonstrating that the CD1 system was present in the last common
      ancestor of mammals and birds at least 300 million years ago. In phylogenetic
      analysis, these sequences cluster with CD1 sequences from other species but are
      not obviously like any particular CD1 isotype. Sequence analysis suggests that
      the expressed proteins bind hydrophobic molecules and are recycled through
      intracellular vesicles. RNA expression is strong in lymphoid tissues but weaker
      to undetectable in some nonlymphoid tissues. Flow cytometry confirms expression
      from one gene on B cells. Based on Southern blotting and cloning, only two such
      CD1 genes are detected, located approximately 800 nucleotides apart and in the
      same transcriptional orientation. The sequence of one gene is nearly identical in
      six chicken lines. By mapping with a backcross family, this gene could not be
      separated from the chicken MHC on chromosome 16. Mining the draft chicken genome
      sequence shows that chicken has only these two CD1 genes located approximately 50
      kb from the classical class I genes. The unexpected location of these genes in
      the chicken MHC suggests the CD1 system was present in the primordial MHC and is
      thus approximately 600 million years old.

PMID- 15939888
TI  - Dynamic reassembly of peptide RADA16 nanofiber scaffold.
AB  - Nanofiber structures of some peptides and proteins as biological materials have
      been studied extensively, but their molecular mechanism of self-assembly and
      reassembly still remains unclear. We report here the reassembly of an ionic self
      complementary peptide RADARADARADARADA (RADA16-I) that forms a well defined
      nanofiber scaffold. The 16-residue peptide forms stable beta-sheet structure and
      undergoes molecular self-assembly into nanofibers and eventually a scaffold
      hydrogel consisting of >99.5% water. In this study, the nanofiber scaffold was
      sonicated into smaller fragments. Circular dichroism, atomic force microscopy,
      and rheology were used to follow the kinetics of the reassembly. These sonicated
      fragments not only quickly reassemble into nanofibers that were indistinguishable
      from the original material, but their reassembly also correlated with the
      rheological analyses showing an increase of scaffold rigidity as a function of
      nanofiber length. The disassembly and reassembly processes were repeated four
      times and, each time, the reassembly reached the original length. We proposed a
      plausible sliding diffusion model to interpret the reassembly involving
      complementary nanofiber cohesive ends. This reassembly process is important for
      fabrication of new scaffolds for 3D cell culture, tissue repair, and regenerative
      medicine.

PMID- 15939889
TI  - Identification of coexpressed gene clusters in a comparative analysis of
      transcriptome and proteome in mouse tissues.
AB  - A major advantage of the mouse model lies in the increasing information on its
      genome, transcriptome, and proteome, as well as in the availability of a fast
      growing number of targeted and induced mutant alleles. However, data from
      comparative transcriptome and proteome analyses in this model organism are very
      limited. We use DNA chip-based RNA expression profiling and 2D gel
      electrophoresis, combined with peptide mass fingerprinting of liver and kidney,
      to explore the feasibility of such comprehensive gene expression analyses.
      Although protein analyses mostly identify known metabolic enzymes and structural
      proteins, transcriptome analyses reveal the differential expression of
      functionally diverse and not yet described genes. The comparative analysis
      suggests correlation between transcriptional and translational expression for the
      majority of genes. Significant exceptions from this correlation confirm the
      complementarities of both approaches. Based on RNA expression data from the 200
      most differentially expressed genes, we identify chromosomal colocalization of
      known, as well as not yet described, gene clusters. The determination of 29 such
      clusters may suggest that coexpression of colocalizing genes is probably rather
      common.

PMID- 15939890
TI  - The selective advantage of microbial fratricide.

PMID- 15939891
TI  - Cytoplasmic LEK1 is a regulator of microtubule function through its interaction
      with the LIS1 pathway.
AB  - LIS1 and nuclear distribution gene E (NudE) are partner proteins in a conserved
      pathway regulating the function of dynein and microtubules. Here, we present data
      that cytoplasmic LEK1 (cytLEK1), a large protein containing a spectrin repeat and
      multiple leucine zippers, is a component of this pathway through its direct
      interaction with NudE, as determined by a yeast two-hybrid screen. We identified
      the binding domains in each molecule, and coimmunoprecipitation and
      colocalization studies confirmed the specificity of the interaction between
      cytLEK1 and NudE. Confocal deconvolution analysis revealed that cytLEK1 exhibits
      colocalization with endogenous NudE and with the known NudE binding partners,
      LIS1 and dynein. By localizing the NudE-binding domain of cytLEK1 to a small
      domain within the molecule, we were able to disrupt cytLEK1 function by using a
      dominant negative approach in addition to LEK1 knockdown and, thus, examine the
      role of the cytLEK1-NudE interaction in cells. Consistent with a defect in the
      LIS1 pathway, disruption of cytLEK1 function resulted in alteration of
      microtubule organization and cellular shape. The microtubule network of cells
      became tightly focused around the nucleus and resulted in a rounded cell shape.
      Additionally, cells exhibited a severe inability to repolymerize their
      microtubule networks after nocodazole challenge. Taken together, our studies
      revealed that cytLEK1 is essential for cellular functions regulated by the LIS1
      pathway.

PMID- 15939894
TI  - Patient n plus 1.

PMID- 15939892
TI  - Concurrent use of transgenic plants expressing a single and two Bacillus
      thuringiensis genes speeds insect adaptation to pyramided plants.
AB  - Transgenic plants expressing insecticidal proteins from the bacterium Bacillus
      thuringiensis (Bt) were grown on over 13 million ha in the United States and 22.4
      million ha worldwide in 2004. Preventing or slowing the evolution of resistance
      by insects ("resistance management") is critical for the sustainable use of Bt
      crops. Plants containing two dissimilar Bt toxin genes in the same plant
      ("pyramided") have the potential to delay insect resistance. However, the
      advantage of pyramided Bt plants for resistance management may be compromised if
      they share similar toxins with single-gene plants that are deployed
      simultaneously. We tested this hypothesis using a unique model system composed of
      broccoli plants transformed to express different Cry toxins (Cry1Ac, Cry1C, or
      both) and a synthetic population of the diamondback moth (Plutella xylostella)
      carrying genes for resistance to Cry1Ac and Cry1C at frequencies of approximately
      0.10 and 0.34, respectively. After 24-26 generations of selection in the
      greenhouse, the concurrent use of one- and two-gene plants resulted in control
      failure of both types of Bt plants. When only two-gene plants were used in the
      selection, no or few insects survived on one- or two-gene Bt plants, indicating
      that concurrent use of transgenic plants expressing a single and two Bt genes
      will select for resistance to two-gene plants more rapidly than the use of two
      gene plants alone. The results of this experiment agree with the predictions of a
      Mendelian deterministic simulation model and have important implications for the
      regulation and deployment of pyramided Bt plants.

PMID- 15939893
TI  - The dense core transmembrane vesicle protein IA-2 is a regulator of vesicle
      number and insulin secretion.
AB  - IA-2 is an enzymatically inactive member of the transmembrane protein tyrosine
      phosphate family located in dense core secretory vesicles and a major autoantigen
      in type 1 diabetes. Recent studies showed that targeted disruption of the IA-2
      gene in mice resulted in impairment of insulin secretion and glucose intolerance.
      Insulin homeostasis, however, is a complex process involving a cascade of
      regulatory factors, and IA-2 is widely expressed in neuroendocrine cells
      throughout the body. Consequently, it is uncertain whether the impairment of
      insulin secretion in IA-2 knockout mice is a direct result of the knockout of IA
      2 in beta cells or to counter regulatory alterations resulting from IA-2 knockout
      in other neuroendocrine cells. To define the function of IA-2, we studied the
      secretion of insulin in a single cell type, MIN-6, by overexpressing and knocking
      down IA-2. Our experiments showed that overexpression of IA-2 resulted in a 6
      fold increase in glucose- or K+-induced insulin secretion and a approximately 3
      fold increase in the number of secretory vesicles and the insulin content of
      cells. In contrast, knockdown of endogenous IA-2 by short interfering RNA
      resulted in nearly a complete loss of glucose-induced insulin secretion and a 50%
      decrease in basal insulin release. The half-life of insulin in cells
      overexpressing IA-2 was nearly twice as great as that in mock-transfected cells,
      suggesting that IA-2 was stabilizing the insulin-containing vesicles. From these
      results we conclude that in beta cells, IA-2 is an important regulator of dense
      core vesicle number and glucose-induced and basal insulin secretion.

PMID- 15939895
TI  - Global IDEA.

PMID- 15939896
TI  - Integrating medical and engineering undergraduate training.

PMID- 15939898
TI  - Global IDEA.

PMID- 15939899
TI  - The study of NOELs.

PMID- 15939900
TI  - The study of NOELs.

PMID- 15939902
TI  - The study of NOELs.

PMID- 15939904
TI  - Ottawa to combine smart regulation and precaution.

PMID- 15939905
TI  - Ads pressure Ontario to butt out in retail locations.

PMID- 15939906
TI  - New malaria combination cheaper and easier to take.

PMID- 15939907
TI  - US health spending up; Medicare expanded.

PMID- 15939908
TI  - Google Scholar: A source for clinicians?

PMID- 15939909
TI  - A drug target for focal segmental glomerulosclerosis.

PMID- 15939910
TI  - Depression: more than just serotonin.

PMID- 15939911
TI  - A young man with palpitations and Ebstein's anomaly of the tricuspid valve.

PMID- 15939912
TI  - Plague: a continuing threat.

PMID- 15939913
TI  - An elderly man with excruciating retrosternal pain and dysphagia.

PMID- 15939914
TI  - Is genetic screening for the Lynch syndrome effective?

PMID- 15939915
TI  - A clinical return-to-work rule for patients with back pain.
AB  - BACKGROUND: Tools for early identification of workers with back pain who are at
      high risk of adverse occupational outcome would help concentrate clinical
      attention on the patients who need it most, while helping reduce unnecessary
      interventions (and costs) among the others. This study was conducted to develop
      and validate clinical rules to predict the 2-year work disability status of
      people consulting for nonspecific back pain in primary care settings. METHODS:
      This was a 2-year prospective cohort study conducted in 7 primary care settings
      in the Quebec City area. The study enrolled 1007 workers (participation, 68.4% of
      potential participants expected to be eligible) aged 18-64 years who consulted
      for nonspecific back pain associated with at least 1 day's absence from work. The
      majority (86%) completed 5 telephone interviews documenting a large array of
      variables. Clinical information was abstracted from the medical files. The
      outcome measure was "return to work in good health" at 2 years, a variable that
      combined patients' occupational status, functional limitations and recurrences of
      work absence. Predictive models of 2-year outcome were developed with a recursive
      partitioning approach on a 40% random sample of our study subjects, then
      validated on the rest. RESULTS: The best predictive model included 7 baseline
      variables (patient's recovery expectations, radiating pain, previous back
      surgery, pain intensity, frequent change of position because of back pain,
      irritability and bad temper, and difficulty sleeping) and was particularly
      efficient at identifying patients with no adverse occupational outcome (negative
      predictive value 78%- 94%). INTERPRETATION: A clinical prediction rule accurately
      identified a large proportion of workers with back pain consulting in a primary
      care setting who were at a low risk of an adverse occupational outcome.

PMID- 15939916
TI  - Vitamin B12, homocysteine and carotid plaque in the era of folic acid
      fortification of enriched cereal grain products.
AB  - BACKGROUND: Carotid plaque area is a strong predictor of cardiovascular events.
      High homocysteine levels, which are associated with plaque formation, can result
      from inadequate intake of folate and vitamin B12. Now that folic acid
      fortification is widespread in North America, vitamin B12 has become an important
      determinant of homocysteine levels. We sought to determine the prevalence of low
      serum levels of vitamin B12, and their relation to homocysteine levels and
      carotid plaque area among patients referred for treatment of vascular disease
      since folic acid fortification of enriched grain products. METHODS: We evaluated
      421 consecutive new patients with complete data whom we saw in our vascular
      disease prevention clinics between January 1998 and January 2002. We measured
      total carotid plaque area by ultrasound and determined homocysteine and serum
      vitamin B12 levels in all patients. RESULTS: The patients, 215 men and 206 women,
      ranged in age from 37 to 90 years (mean 66 years). Most were taking medications
      for hypertension (67%) and dyslipidemia (62%). Seventy-three patients (17%) had
      vitamin B12 deficiency (vitamin B12 level < 258 pmol/L with homocysteine level >
      14 mumol/L or methylmalonic acid level > 271 nmol/L). The mean area of carotid
      plaque was significantly larger among the group of patients whose vitamin B12
      level was below the median of 253 pmol/L than among those whose vitamin B12 level
      was above the median: 1.36 (standard deviation [SD] 1.27) cm2 v. 1.09 (SD 1.0)
      cm2; p = 0.016. CONCLUSIONS: Vitamin B12 deficiency is surprisingly common among
      patients with vascular disease, and, in the setting of folic acid fortification,
      low serum vitamin B12 levels are a major determinant of elevated homocysteine
      levels and increased carotid plaque area.

PMID- 15939917
TI  - Clinical prediction rule for return to work after back pain.

PMID- 15939918
TI  - Borderline personality disorder.
AB  - Borderline personality disorder is a chronic psychiatric disorder characterized
      by marked impulsivity, instability of mood and interpersonal relationships, and
      suicidal behaviour that can complicate medical care. Identifying this diagnosis
      is important for treatment planning. Although the cause of borderline personality
      disorder is uncertain, most patients improve with time. There is an evidence base
      for treatment using both psychotherapy and psychopharmacology. The clinical
      challenge centres on managing chronic suicidality.

PMID- 15939919
TI  - Bladder cancer "adjuvant-lite": tastes great (works as well) and less filling
      (less toxic)?

PMID- 15939920
TI  - Adjuvant cisplatin plus methotrexate versus methotrexate, vinblastine,
      epirubicin, and cisplatin in locally advanced bladder cancer: results of a
      randomized, multicenter, phase III trial (AUO-AB 05/95).
AB  - PURPOSE: Radical cystectomy as standard treatment of muscle-invasive urothelial
      carcinoma of the urinary bladder cures less than 50% of patients with locally
      advanced bladder cancer. We compared two adjuvant combination chemotherapies in
      patients with stage pT3a-4a and/or pathologic node-positive transitional-cell
      carcinoma of the bladder after radical cystectomy. PATIENTS AND METHODS: A total
      of 327 patients were randomly assigned to either adjuvant systemic chemotherapy
      with three cycles of cisplatin 70 mg/qm(2) on day 1 and methotrexate 40 mg/qm(2)
      on days 8 and 15 of a 21-day cycle (CM) or three cycles of methotrexate 30
      mg/qm(2) on days 1, 15, and 22, vinblastine 3 mg/qm(2) on days 2, 15, and 22,
      epirubicin 45 mg/qm(2) on day 2, and cisplatin 70 mg/qm(2) on day 2 of a 28-day
      cycle (M-VEC). RESULTS: The hazard ratio for progression-free survival as the
      primary end point was 1.13 (90% CI, 0.86 to 1.48) for 163 CM patients compared
      with 164 M-VEC patients whose right-hand limit remained below the upper bound
      compatible with the noninferiority hypothesis (alpha = .0403). The 5-year
      progression-free, tumor-specific, and overall survival rates (point estimates +/-
      SE) for CM versus M-VEC were 46.3% +/- 4.6% v 48.8% +/- 4.5%, 52.0% +/- 4.6% v
      52.3% +/- 4.8%, and 46.1% +/- 4.3% v 45.1% +/- 4.6%, respectively. WHO grade 3
      and 4 leukopenia occurred in 7.0% of patients treated with CM and 22.2% of
      patients treated with M-VEC (P < .0001). CONCLUSION: CM cannot be considered
      inferior to M-VEC with regard to progression-free survival of patients with
      locally advanced bladder cancer after radical cystectomy. Moreover, patients
      receiving adjuvant CM combination therapy experienced significantly less grade 3
      and 4 leukopenia than patients treated with M-VEC.

PMID- 15939921
TI  - Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced
      breast cancer.
AB  - PURPOSE: To evaluate the antitumor activity and pharmacodynamic/biologic effect
      of gefitinib 500 mg/day monotherapy in patients with previously treated, advanced
      breast cancer. METHODS: In this phase II multicenter trial, the primary objective
      was assessment of the tumor response rate with gefitinib; secondary objectives
      included analysis of the pharmacodynamic and biologic profiles in healthy and
      tumor tissue. RESULTS: while phosphorylation of mitogen-activated protein kinase
      was inhibited in both tissues, gefitinib treatment induced p27 and a decrease in
      Ki67 in skin but not in tumors. Furthermore, gefitinib did not inhibit the
      activated form of Akt in the tumors. CONCLUSION: This study demonstrates a good
      correlation between the degree of inhibition of EGFR in skin and in breast
      tumors. The lack of significant clinical activity of gefitinib in our study
      population is not due to lack of receptor inhibition in these tumors but rather
      to lack of EGFR dependence in the tested population.

PMID- 15939922
TI  - Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced
      colorectal cancer: a multicenter study of the Gruppo Oncologico Dell'Italia
      Meridionale.
AB  - PURPOSE: We performed this phase III study to compare the irinotecan, leucovorin
      (LV), and fluorouracil (FU) regimen (FOLFIRI) versus the oxaliplatin, LV, and FU
      regimen (FOLFOX4) in previously untreated patients with advanced colorectal
      cancer. PATIENTS AND METHODS: A total of 360 chemotherapy-naive patients were
      randomly assigned to receive, every 2 weeks, either arm A (FOLFIRI: irinotecan
      180 mg/m(2) on day 1 with LV 100 mg/m(2) administered as a 2-hour infusion before
      FU 400 mg/m(2) administered as an intravenous bolus injection, and FU 600 mg/m(2)
      as a 22-hour infusion immediately after FU bolus injection on days 1 and 2
      [LV5FU2]) or arm B (FOLFOX4: oxaliplatin 85 mg/m(2) on day 1 with LV5FU2
      regimen). RESULTS: One hundred sixty-four and 172 patients were assessable in arm
      A and B, respectively. Overall response rates (ORR) were 31% in arm A (95% CI,
      24.6% to 38.3%) and 34% in arm B (95% CI, 27.2% to 41.5%; P = .60). In both arms
      A and B, median time to progression (TTP; 7 v 7 months, respectively), duration
      of response (9 v 10 months, respectively), and overall survival (OS; 14 v 15
      months, respectively) were similar, without any statistically significant
      difference. Toxicity was mild in both groups: alopecia and gastrointestinal
      disturbances were the most common toxicities in arm A; thrombocytopenia and
      neurosensorial were the most common toxicities in arm B. Grade 3 to 4 toxicities
      were uncommon in both arms, and no statistical significant difference was
      observed. CONCLUSION: There is no difference in ORR, TTP, and OS for patients
      treated with the FOLFIRI or FOLFOX4 regimen. Both therapies seemed effective as
      first-line treatment in these patients. The difference between these two
      combination therapies is mainly in the toxicity profile.

PMID- 15939923
TI  - Phase III study of weekly high-dose infusional fluorouracil plus folinic acid
      with or without irinotecan in patients with metastatic colorectal cancer:
      European Organisation for Research and Treatment of Cancer Gastrointestinal Group
      Study 40986.
AB  - PURPOSE: To demonstrate that adding irinotecan to a standard weekly schedule of
      high-dose, infusional fluorouracil (FU) and leucovorin (folinic acid [FA]) can
      prolong progression-free survival (PFS). PATIENTS AND METHODS: Four hundred
      thirty patients with measurable or assessable metastatic colorectal cancer were
      randomly assigned to receive either FA 500 mg/m(2) as a 2-hour infusion and FU
      2.6 g/m(2) by intravenous 24-hour infusion, both administered weekly for 6 weeks,
      followed by a 2-week rest (Arbeitsgemeinschaft fur Internistische Onkologie [AIO]
      arm, n = 216), or a similar schedule but with FU 2.3 or 2.0 g/m(2) preceded by
      irinotecan 80 mg/m(2) administered over 30 minutes (experimental group, n = 214).
      RESULTS: The median PFS time in the experimental group was 8.5 months (95% CI,
      7.6 to 9.9 months) compared with 6.4 months (95% CI, 5.3 to 7.2 months) in the
      AIO arm (P < .0001). The median overall survival time was increased from 16.9 to
      20.1 months (P = .2779). The objective response rate was 62.2% (95% CI, 55.0% to
      69.5%) in the experimental group and 34.4% (95% CI, 27.5% to 41.3%) in the AIO
      arm (P < .0001). CONCLUSION: The addition of irinotecan to the standard AIO FU/FA
      regimen was associated with a highly significant improvement in PFS and response
      rate and was well tolerated. The results of this study confirm that irinotecan in
      combination with high-dose infusional FU/FA is a reference first-line treatment.

PMID- 15939924
TI  - Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of
      patients with active multiple myeloma.
AB  - PURPOSE: To study the antiangiogenic effect of thalidomide. PATIENTS AND METHODS:
      The expression of key angiogenic genes was studied in bone marrow endothelial
      cells (ECs) of patients with active and nonactive multiple myeloma (MM),
      monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell
      non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy
      human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of
      thalidomide. RESULTS: Thalidomide markedly downregulates the genes in a dose
      dependent fashion in active MMECs and KS cell line, but upregulates them or is
      ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of
      vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF)
      and hepatocyte growth factor also diminishes according to the dose in culture
      conditioned media (CM) of active MMECs and KS, whereas it does not change in the
      other CM. CONCLUSION: Inhibition by thalidomide is probably confined to the genes
      of active MMECs and KS. This would account for its higher efficacy in these
      diseases.

PMID- 15939925
TI  - Phase I and pharmacokinetic study of LY293111, an orally bioavailable LTB4
      receptor antagonist, in patients with advanced solid tumors.
AB  - PURPOSE: LY293111, a novel diaryl ether carboxylic acid derivative, is a potent
      and selective inhibitor of the lipoxygenase pathway either directly through 5'
      lipoxygenase or via antagonism of the leukotriene B4 (LTB4) receptor. More
      recently it has been determined to have peroxisome proliferator activated
      receptor-gamma agonist (PPARgamma) activity. LY293111 has antineoplastic activity
      in a variety of preclinical models. The tolerability and pharmacokinetics of
      LY293111 administered continuously, by mouth, BID for repeat cycles of 21 days
      was evaluated. PATIENTS AND METHODS: Thirty-eight patients with advanced solid
      tumors were treated at five dose levels (200 to 800 mg BID) for a total of 102
      cycles. RESULTS: The most common toxicity was diarrhea (76%). One patient at 600
      mg BID (n = 11) and two at 800 mg BID (n = 8), experienced dose-limiting grade 3
      diarrhea. Dose reductions and/or delays were infrequent. Increases in steady
      state maximum plasma concentration (Cmax,ss) and area under the steady-state
      plasma concentration time curve 0 to 12 hours (AUCtau,ss) on day 8 could be
      considered to be dose-proportional over the four-fold-dose range. Interpatient
      variability in Cmax,ss and AUCtau,ss was estimated to be 65% and 71%
      respectively. There was a small increase in AUC (1.37; 90% CI, 0.85 to 2.21)
      between single and multiple doses. Two patients with progressive chondrosarcoma
      and melanoma had stable disease lasting approximately 336 and 168 days,
      respectively. CONCLUSION: LY293111 can be administered safely by continuous oral
      therapy with mild toxicities. Diarrhea is dose-limiting. The recommended phase II
      dose will be 600 mg BID. The steady-state concentrations in humans exceed
      relevant levels observed in preclinical models.

PMID- 15939926
TI  - Creeping phase II-ism and the medical pharmaceutical complex: weapons of mass
      distraction in the war against lung cancer.

PMID- 15939927
TI  - Effect of individual psychological intervention in Chinese women with gynecologic
      malignancy: a randomized controlled trial.
AB  - PURPOSE: To evaluate the effectiveness of psychological intervention in the care
      of cancer patients and to determine whether routine use of individual
      psychological therapies is indicated. PATIENTS AND METHODS: Patients with newly
      diagnosed gynecologic malignancies from August 1999 to November 2000 were
      recruited and randomly assigned to either a control group receiving routine
      medical care or to an intervention group receiving individual psychotherapy. A
      set of fixed-choice, self-report questionnaires assessing the patients'
      psychological status, quality of life, and their perceptions related to the
      medical consultations was completed at recruitment and then every 3 months for 18
      months. Data analysis was performed according to the intention-to-treat principle
      by fitting the data into a linear mixed-effects model. Multivariable analyses
      were performed to examine the effects of confounding factors. RESULTS: One
      hundred fifty-five patients participated in the trial. There were no
      statistically significant differences between the two groups at baseline. There
      was a trend toward better quality of life and functional status and also
      improvement of the symptoms over time for both groups. No differences were found
      between the groups in the scores measured by any of the instruments at baseline
      and at any time points after the cancer diagnosis. Psychological intervention had
      no significant effects on the psychosocial parameters. CONCLUSION: Routine use of
      psychological therapies as given in our format has no significant effect on the
      patients' quality of life and psychological status.

PMID- 15939928
TI  - Whither irinotecan?

PMID- 15939929
TI  - How and for whom? Asking questions about the utility of psychosocial
      interventions for individuals diagnosed with cancer.

PMID- 15939930
TI  - Study of paclitaxel, etoposide, and cisplatin chemotherapy combined with twice
      daily thoracic radiotherapy for patients with limited-stage small-cell lung
      cancer: a Radiation Therapy Oncology Group 9609 phase II study.
AB  - PURPOSE: To determine the response rate, progression-free survival and overall
      survival, and toxicity of paclitaxel, etoposide, and cisplatin combined with
      accelerated hyperfractionated thoracic radiotherapy in patients with limited
      disease (LD) small-cell lung cancer (SCLC). PATIENTS AND METHODS: LD-SCLC
      patients with measurable disease, Karnofsky performance score of > or = 70, and
      adequate organ function who were previously untreated were eligible for the
      study. Treatment was as follows. In cycle 1 of chemotherapy, concurrent thoracic
      radiation therapy was administered. In cycles 2 to 4, chemotherapy was
      administered alone. In cycle 1, chemotherapy consisted of paclitaxel 135 mg/m(2)
      intravenous over 3 hours on day 1, etoposide 60 mg/m(2) intravenous on day 1 and
      80 mg/m(2) orally on days 2 and 3, and cisplatin 60 mg/m(2) intravenous on day 1.
      In cycles 2 to 4, the paclitaxel dose was increased to 175 mg/m(2), with the
      etoposide and cisplatin doses remaining the same as in cycle 1. The thoracic
      radiation therapy consisted of 1.5 Gy in 30 fractions (total dose, 45 Gy)
      administered 5 days a week for 3 weeks. RESULTS: Fifty-five patients were
      enrolled onto the study, and 53 were assessable. The major toxicities included
      grade 3 and 4 acute neutropenia (32% and 43%, respectively) and grade 3 and 4
      esophagitis (32% and 4%, respectively). Two patients died as a result of therapy
      (one died of acute respiratory distress syndrome, and one died of sepsis). There
      was one late fatal pulmonary toxicity. The median survival time was 24.7 months.
      The 2-year survival rate was 54.7%. The median progression-free survival time was
      13 months, with a 2-year progression-free survival rate of 26.4%. CONCLUSION:
      Although this therapeutic regimen is effective in the treatment of patients with
      LD-SCLC, it is unlikely that the three-drug combination with thoracic radiation
      therapy will improve the survival times compared with the etoposide plus
      cisplatin chemotherapy regimen with thoracic radiation therapy in LD-SCLC
      patients.

PMID- 15939931
TI  - DNA microarrays on a dendron-modified surface improve significantly the detection
      of single nucleotide variations in the p53 gene.
AB  - Selectivity and sensitivity in the detection of single nucleotide polymorphisms
      (SNPs) are among most important attributes to determine the performance of DNA
      microarrays. We previously reported the generation of a novel mesospaced surface
      prepared by applying dendron molecules on the solid surface. DNA microarrays that
      were fabricated on the dendron-modified surface exhibited outstanding performance
      for the detection of single nucleotide variation in the synthetic oligonucleotide
      DNA. DNA microarrays on the dendron-modified surface were subjected to the
      detection of single nucleotide variations in the exons 5-8 of the p53 gene in
      genomic DNAs from cancer cell lines. DNA microarrays on the dendron-modified
      surface clearly discriminated single nucleotide variations in hotspot codons with
      high selectivity and sensitivity. The ratio between the fluorescence intensity of
      perfectly matched duplexes and that of single nucleotide mismatched duplexes was
      >5-100 without sacrificing signal intensity. Our results showed that the
      outstanding performance of DNA microarrays fabricated on the dendron-modified
      surface is strongly related to novel properties of the dendron molecule, which
      has the conical structure allowing mesospacing between the capture probes. Our
      microarrays on the dendron-modified surface can reduce the steric hindrance not
      only between the solid surface and target DNA, but also among immobilized capture
      probes enabling the hybridization process on the surface to be very effective.
      Our DNA microarrays on the dendron-modified surface could be applied to various
      analyses that require accurate detection of SNPs.

PMID- 15939932
TI  - NMR structure and Mg2+ binding of an RNA segment that underlies the L7/L12 stalk
      in the E.coli 50S ribosomal subunit.
AB  - Helix 42 of Domain II of Escherichia coli 23S ribosomal RNA underlies the L7/L12
      stalk in the ribosome and may be significant in positioning this feature relative
      to the rest of the 50S ribosomal subunit. Unlike the Haloarcula marismortui and
      Deinococcus radiodurans examples, the lower portion of helix 42 in E.coli
      contains two consecutive G*A oppositions with both adenines on the same side of
      the stem. Herein, the structure of an analog of positions 1037-1043 and 1112-1118
      in the helix 42 region is reported. NMR spectra and structure calculations
      support a cis Watson-Crick/Watson-Crick (cis W.C.) G*A conformation for the
      tandem (G*A)2 in the analog and a minimally perturbed helical duplex stem. Mg2+
      titration studies imply that the cis W.C. geometry of the tandem (G*A)2 probably
      allows O6 of G20 and N1 of A4 to coordinate with a Mg2+ ion as indicated by the
      largest chemical shift changes associated with the imino group of G20 and the H8
      of G20 and A4. A cross-strand bridging Mg2+ coordination has also been found in a
      different sequence context in the crystal structure of H.marismortui 23S rRNA,
      and therefore it may be a rare but general motif in Mg2+ coordination.

PMID- 15939933
TI  - Structural properties of promoters: similarities and differences between
      prokaryotes and eukaryotes.
AB  - During the process of transcription, RNA polymerase can exactly locate a promoter
      sequence in the complex maze of a genome. Several experimental studies and
      computational analyses have shown that the promoter sequences apparently possess
      some special properties, such as unusual DNA structures and low stability, which
      make them distinct from the rest of the genome. But most of these studies have
      been carried out on a particular set of promoter sequences or on promoter
      sequences from similar organisms. To examine whether the promoters from a wide
      variety of organisms share these special properties, we have carried out an
      analysis of sets of promoters from bacteria, vertebrates and plants. These
      promoters were analyzed with respect to the prediction of three different
      properties, such as DNA curvature, bendability and stability, which are relevant
      to transcription. All the promoter sequences are predicted to share certain
      features, such as stability and bendability profiles, but there are significant
      differences in DNA curvature profiles and nucleotide composition between the
      different organisms. These similarities and differences are correlated with some
      of the known facts about transcription process in the promoters from the three
      groups of organisms.

PMID- 15939935
TI  - Reducing reductionism: reclaiming psychiatry.

PMID- 15939934
TI  - Functional analysis of the N- and C-terminus of mammalian G9a histone H3
      methyltransferase.
AB  - Methylation of lysine 9 (K9) in the N-terminus tail of histone H3 (H3) in
      chromatin is associated with transcriptionally silenced genes and is mediated by
      histone methyltransferases. Murine G9a is a 1263 amino acid H3-K9
      methyltransferase that possesses characteristic SET domain and ANK repeats. In
      this paper, we have used a series of green fluorescent protein-tagged deletion
      constructs to identify two nuclear localization signals (NLS), the first NLS
      embedded between amino acids 24 and 109 and the second between amino acids 394
      and 401 of murine G9a. Our data show that both long and short G9a isoforms were
      capable of entering the nucleus to methylate chromatin. Full-length or N-terminus
      deleted G9a isoforms were also catalytically active enzymes that methylated
      recombinant H3 or synthetic peptides representing the N-terminus tail of H3. In
      vitro methylation reactions using N-terminus tail peptides resulted in tri
      methylation of K9 that remained processive, even in G9a enzymes that lacked an N
      terminus region by deletion. Co-expression of G9a and H3 resulted in di- and tri
      methylation of H3-K9, while siRNA-mediated knockdown of G9a in HeLa cells
      resulted in reduction of global H3-K9 di- and tri-methylation. A recombinant
      deletion mutant enzyme fused with maltose-binding protein (MBP-G9aDelta634) was
      used for steady-state kinetic analysis with various substrates and was compared
      with full-length G9a (G9aFL). Turnover numbers of MBP-G9aDelta634 for various
      substrates was approximately 3-fold less compared with G9aFL, while their
      Michaelis constants (K(m)) for recombinant H3 were similar. The K(AdoMet)m for
      MBP-G9aDelta634 was approximately 2.3-2.65 microM with various substrates.
      Catalytic efficiencies (kcat/K(m)) for both MBP-G9aDelta634 and G9aFL were
      similar, suggesting that the N-terminus is not essential for catalysis.
      Furthermore, mutation of conserved amino acids R1097A, W1103A, Y1120A, Y1138A and
      R1162A, or the metal binding C1168A in the catalytic region, resulted in
      catalytically impaired enzymes, thereby confirming the involvement of the C
      terminus of G9a in catalysis. Thus, distinct domains modulate nuclear targeting
      and catalytic functions of G9a.

PMID- 15939936
TI  - Proposition 63: should other states follow California's lead?

PMID- 15939937
TI  - Economic grand rounds: the economics of the new medicare drug benefit:
      implications for people with mental illnesses.

PMID- 15939938
TI  - Components of spending for Medicaid Mental Health Services, 2001.

PMID- 15939939
TI  - Psychopharmacology: the need for effectiveness trials to inform evidence-based
      psychiatric practice.

PMID- 15939940
TI  - Best practices: reducing rehospitalization with telephonic targeted care
      management in a managed health care plan.

PMID- 15939941
TI  - The story of Margery Kempe.

PMID- 15939942
TI  - Trends in U.S. emergency department visits for mental health conditions, 1992 to
      2001.
AB  - OBJECTIVE: The objective of this study was to ascertain trends in mental health
      related visits to U.S. emergency departments. METHODS: Data were obtained from
      the National Hospital Ambulatory Medical Care Survey by using mental health
      related ICD-9-CM, E, and V codes as well as mental health-related reasons for
      visit. RESULTS: From 1992 to 2001, there were 53 million mental health-related
      visits, representing an increase from 4.9 percent to 6.3 percent of all emergency
      department visits and an increase from 17.1 to 23.6 visits per 1,000 U.S.
      population across the decade. The most prevalent diagnoses were substance-related
      disorders (22 percent of visits), mood disorders (17 percent), and anxiety
      disorders (16 percent). Mental health-related visits increased significantly
      among non-Hispanic whites, patients older than 70 years, and patients with
      insurance. Medications were administered during 61 percent of all mental health
      related visits, most commonly psychotropic medication, the prescription rate of
      which increased from 22 percent to 31 percent of visits over the decade. Ten-year
      increases in mental health-related emergency department visits were significant
      for all U.S. geographic regions except the Midwest. CONCLUSIONS: Mental health
      related visits constitute a significant and increasing burden of care in U.S.
      emergency departments.

PMID- 15939943
TI  - High utilizers of psychiatric emergency services.
AB  - OBJECTIVE: The purpose of this study was to examine the sociodemographic and
      clinical characteristics of high utilizers of psychiatric emergency services.
      METHODS: Data were collected over four years for 761 patients who were identified
      as high utilizers according to three definitions (two standard deviations above
      the mean number of visits to an urban psychiatric emergency service, six visits
      in a year, and four visits in a quarter) and for 1,585 nonfrequent utilizers
      (control group). Univariate analysis of variance and logistic regression models
      were used to determine group differences. RESULTS: Two distinct groups of high
      utilizers emerged: high utilizers by quarter and high utilizers by standard
      deviation. Compared with the control group, the high utilizers were more likely
      to be homeless, to have developmental delays, to be enrolled in a mental health
      plan, to have a history of voluntary and involuntary hospitalizations, to be
      uncooperative, to have personality disorders, to have unreliable social support,
      and to have a lifetime history of incarceration and detoxification. Compared with
      the high utilizers by quarter, the high utilizers by standard deviation had more
      visits and were more likely to have a history of incarceration and psychiatric
      hospitalization, more likely to be enrolled in mental health plan, and less
      likely to be homeless. CONCLUSIONS: High utilizers make up a small percentage of
      individuals who seek care in psychiatric emergency services and
      disproportionately use resources. It may be helpful to use two definitions of
      high utilizer to identify patients at different phases of their illness and to
      guide clinical interventions and mental health policies.

PMID- 15939944
TI  - The impact of capitated financing on psychiatric emergency services.
AB  - OBJECTIVE: Studies of capitated financing of mental health services have
      generally focused on the cost and utilization of services. Relatively little
      research has addressed whether capitation has an impact on the effectiveness of
      the mental health system as a whole. This study examined the impact of capitation
      on hospital emergency department visits, a widely cited indicator of the
      effectiveness of the other components of the system. METHODS: In 1995 Colorado's
      Medicaid program instituted capitation for mental health services in two areas of
      the state, one in which reimbursement of not-for-profit providers was directly
      capitated and another in which not-for-profit providers partnered with a for
      profit managed behavioral health organization. The analysis examined variation
      over time in the number of emergency department visits by adults who had a
      primary mental or substance use disorder. Using interrupted time-series methods,
      visits in areas where reimbursement was capitated were compared with visits in
      areas where providers continued to be reimbursed on a fee-for-service basis. A
      total of 105 weeks for each area was examined; capitation was implemented at week
      53. RESULTS: The number of psychiatric emergencies treated in capitated areas
      declined by 814 (28 percent) below the 2,908 psychiatric emergencies expected
      from trends, cycles, and levels in fee-for-service areas. Findings were similar
      for for-profit and not-for-profit areas. The decrease persisted through the end
      of the first year after capitation. CONCLUSIONS: In Colorado the implementation
      of capitation was associated with a sustained decrease in utilization of
      psychiatric emergency services provided by hospital emergency departments. Our
      findings suggest that capitation does not necessarily reduce the quality of care
      provided to clients.

PMID- 15939945
TI  - Psychiatric emergency service use after implementation of managed care in a
      public mental health system.
AB  - OBJECTIVE: This study examined whether implementation of managed care in a public
      mental health system affected return visits to psychiatric emergency services
      within 180 days of an index visit. METHODS: Data were taken from an
      administrative database of 75,815 patient visits made to a hospital-based
      psychiatric emergency service for mental health care between January 1, 1995, and
      December 31, 2002. Rates of return visits for patients whose index visit occurred
      at least 26 weeks before a system of managed care was implemented in 1999 were
      compared with rates for patients whose index visit occurred after the
      implementation but at least 26 weeks before the data collection period ended.
      Declining-effects modeling was used to adjust for patients' gender, ethnicity,
      age, and admission status. RESULTS: A total of 37,371 patients met study criteria
      for inclusion: 21,135 before managed care was implemented and 16,236 after
      managed care was implemented. In the pre-managed care group, 3,687 patients (17
      percent) made a repeat visit within 26 weeks of their index visit; 2,369 patients
      (15 percent) in the post-managed care group made such a repeat visit. For any
      given index visit to the psychiatric emergency department, patients who presented
      for treatment after managed care were only 90 percent as likely as patients who
      presented before managed care to have a return visit within the first five weeks
      after the index visit. However, there was essentially no difference between
      groups in the likelihood of a return visit by week 26 after the index visit,
      suggesting that managed care delayed, but did not eliminate, return visits. In
      addition, the number of police-accompanied index visits continued to rise after
      managed care was implemented (from 32.0 to 52.6 percent of all index visits),
      suggesting that increasing numbers of patients with mental illness in need of
      treatment were coming to the attention of law enforcement officials after managed
      care was implemented. CONCLUSIONS: Managed care strategies are often used to
      reduce reliance on emergency services. In this study, managed care delayed,
      rather than prevented, return visits to the psychiatric emergency service.

PMID- 15939946
TI  - Psychiatric emergency service use and homelessness, mental disorder, and
      violence.
AB  - OBJECTIVE: This study examined relationships between homelessness, mental
      disorder, violence, and the use of psychiatric emergency services. To the
      authors' knowledge, this study is the first to examine these issues for all
      episodes of care in a psychiatric emergency service that serves an entire mental
      health system in a major city. METHODS: Archival databases were examined to
      gather data on all individuals (N=2,294) who were served between January 1, 1997,
      and June 30, 1997, in the county hospital's psychiatric emergency service in San
      Francisco, California. RESULTS: Homeless individuals accounted for approximately
      30 percent of the episodes of service in the psychiatric emergency service and
      were more likely than other emergency service patients to have multiple episodes
      of service and to be hospitalized after the emergency department visit.
      Homelessness was associated with increased rates of co-occurring substance
      related disorders and severe mental disorders. Eight percent of persons who were
      homeless had exhibited violent behavior in the two weeks before visiting the
      emergency service. CONCLUSIONS: Homeless individuals with mental disorders
      accounted for a large proportion of persons who received psychiatric emergency
      services in the community mental health system in the urban setting of this
      study. The co-occurrence of homelessness, mental disorder, substance abuse, and
      violence represents a complicated issue that will likely require coordination of
      multiple service delivery systems for successful intervention. These findings
      warrant consideration in public policy initiatives. Simply diverting individuals
      with these problems from the criminal justice system to the community mental
      health system may have limited impact unless a broader array of services can be
      brought to bear.

PMID- 15939947
TI  - The role of Afro-Canadian status in police or ambulance referral to emergency
      psychiatric services.
AB  - OBJECTIVE: This study tested the hypothesis that among patients admitted to a
      hospital with psychosis, Afro-Canadian patients would be more likely than Euro
      Canadian or Asian-Canadian patients to be brought to emergency services by police
      or ambulance. METHODS: Data on psychotic patients admitted to the psychiatry ward
      in 1999 were extracted from records of a general hospital in Montreal. Logistic
      regression models examined the relationship between being Afro-Canadian and being
      brought to the emergency service by police or ambulance, while controlling for
      age, gender, marital status, and number of psychotic symptoms. RESULTS: Of the
      351 patients with psychosis, 59 percent were Euro-Canadian, 11 percent were Afro
      Canadian, and 18 percent were Asian Canadian. Most Afro-Canadian patients in the
      study were immigrants from the Caribbean and Africa. Being Afro-Canadian was
      independently and positively associated with police or ambulance referral to
      emergency services. CONCLUSIONS: Afro-Canadians admitted to the hospital with
      psychosis are overrepresented in police and ambulance referrals to emergency
      psychiatric services.

PMID- 15939948
TI  - Ethnic differences in prediction of violence risk with the HCR-20 among
      psychiatric inpatients.
AB  - OBJECTIVE: This study examined ethnic differences in assessment of violence risk
      among psychiatric inpatients by using the Historical Clinical Risk Management-20
      (HCR-20). METHODS: The HCR-20 was administered to 169 consecutive psychiatric
      inpatients. Individual items and total scores on the HCR-20 were compared between
      patients of Asian-American (N=51), Euro-American (N=46), and Native-Hawaiian
      (N=38) heritage. Receiver operating characteristic (ROC) and stepwise regressions
      were calculated for each ethnic group with HCR-20 scores as predictor variables
      and violent event reports of significant threats and assaults as the outcome
      measure. RESULTS: Similar rates of overall violence were found between ethnic
      groups, and the HCR-20 was found to have predictive validity as measured by ROC
      analysis. Differences in scores on individual HCR-20 items were found, including
      young age at first incident of violence, psychopathy, early maladjustment,
      personality disorder, and past supervision failure, as well as total HCR-20
      score, with Asian Americans scoring lower (less risk) than Euro-Americans and
      Native Hawaiians. Stepwise multiple regressions indicated a different pattern of
      predictor variables for each ethnic group, with impulsivity salient for the Asian
      American group, young age at first incident of violence salient for the Euro
      American group, and young age at first incident of violence, relationship
      instability, and risk-management plans' lacking feasibility as salient predictors
      for the Native-Hawaiian group. CONCLUSIONS: The findings provide preliminary
      support for the cross-cultural validity of the HCR-20 while at the same time
      identifying unique ethnic differences in prediction of violence risk among
      psychiatric inpatients.

PMID- 15939949
TI  - Depression among Latina immigrant mothers separated from their children.
AB  - OBJECTIVE: Latinas who immigrate to the United States and leave their children in
      their homelands may experience psychological consequences of this separation.
      This study examined whether immigrant Latinas who were separated from their
      children differed in rates of probable major depression from those who lived with
      their children and from those who did not have any children. METHODS: Data were
      obtained between March 1997 and May 2002 from women in Women, Infants, and
      Children programs that target low-income pregnant and postpartum women and their
      children (up to five years of age), women in county-run Title X family planning
      clinics, women in pediatric clinics for low-income families, and women who were
      living in a subsidized-housing project or attending programs for county welfare
      recipients. Latinas in this study were all immigrants to the United States. The
      women were screened for major depressive disorders with the Primary Care
      Evaluation of Mental Disorders. RESULTS: A total of 5,122 Latina immigrants were
      screened. Overall, 11.7 percent of the sample screened positive for major
      depression. The rates of depression were 11.4 percent for women who lived with
      their children, 10.9 percent for those who did not have children, and 18.1 for
      those who were not living with their children. When the analyses controlled for
      demographic differences, the odds of depression for immigrant Latinas who were
      separated from their children were 1.52 times as great as the odds for those
      whose children were currently living with them (p=.02). Odds of depression were
      similar among women who lived with their children and those who did not have
      children. CONCLUSIONS: Separation from children during immigration may lead to
      increased risk of depression for immigrant Latinas. Health care clinicians who
      treat young immigrant women should pay close attention to signs of depression
      among women who have left children with relatives in their homelands.

PMID- 15939950
TI  - Race, gender, and psychiatrists' diagnosis and treatment of major depression
      among elderly patients.
AB  - OBJECTIVE: This study examined psychiatrists' contributions to racial and gender
      disparities in diagnosis and treatment among elderly persons. METHODS:
      Psychiatrists who volunteered to participate in the study were randomly assigned
      to one of four video vignettes depicting an elderly patient with late-life
      depression. The vignettes differed only in terms of the race of the actor
      portraying the patient (white or African American) and gender. The study
      participants were 329 psychiatrists who attended the 2002 annual meeting of the
      American Psychiatric Association. RESULTS: Eighty-one percent of the
      psychiatrists assigned the elderly patient a diagnosis of major depression.
      Patients' race and gender was not associated with significant differences in the
      diagnoses of major depression, assessment of most patient characteristics, or
      recommendations for managing the disorder. However, psychiatrists'
      characteristics, particularly the location of the medical school at which the
      psychiatrist was trained (United States versus international), were significantly
      associated with a number of variables. CONCLUSIONS: Given standardized symptom
      pictures, psychiatrists are no less likely to diagnose or treat depression among
      African-American elderly patients than among other patients, which suggests that
      bias based simply on race is not a likely explanation for racial differences in
      diagnosis and treatments found in earlier clinical studies. The impact of
      psychiatrists' having trained at international medical schools on diagnosis,
      treatment, and judgment of several patient attributes may indicate the need for
      targeted educational initiatives for aging and cultural competency.

PMID- 15939952
TI  - Recovery from schizophrenia: a concept in search of research.

PMID- 15939951
TI  - Access to specialty mental health services among women in California.
AB  - OBJECTIVE: The Anderson behavioral model was used to investigate racial and
      ethnic disparities in access to specialty mental health services among women in
      California as well as factors that might account for such disparities. METHODS:
      The study was a cross-sectional examination of a probability sample of 3,750
      California women. The main indicators of access to services were perceived need,
      service seeking, and service use. Multivariate models were constructed that
      accounted for need and enabling and demographic variables. RESULTS: Significant
      racial and ethnic variations in access to specialty mental health services were
      observed. African-American, Hispanic, and Asian women were significantly less
      likely to use specialty mental health services than white women. Multivariate
      analyses showed that Hispanic and Asian women were less likely than white women
      to report perceived need, even after frequent mental distress had been taken into
      account. Among women with perceived need, African-American and Asian women were
      less likely than white women to seek mental health services after differences in
      insurance status had been taken into account. Among women who sought services,
      Hispanic women were less likely than white women to obtain services after
      adjustment for the effects of poverty. Need and enabling factors did not entirely
      account for the observed disparities in access to services. CONCLUSIONS:
      Additional research is needed to identify gender- and culture-specific models for
      access to mental health services in order to decrease disparities in access.
      Factors such as perceived need and decisions to seek services are important
      factors that should be emphasized in future studies.

PMID- 15939953
TI  - Service expectations and clinical characteristics of patients receiving
      psychiatric emergency services.
AB  - Previous studies suggest that patients use medical emergency departments for
      nonurgent care. However, relatively little has been published about the use of
      psychiatric emergency services. Eighty-two patients who visited the psychiatric
      emergency department in a free-standing psychiatric hospital during July 2003
      participated in a self-report survey about patients' expectations. Almost all
      respondents had acute psychiatric needs on presentation to the psychiatric
      emergency department, and 45 (75 percent) had urgent needs that required
      inpatient or partial hospitalization. However, there was considerable mismatch
      between some patients' expectations and the types of services available.
      Patients' use of this psychiatric emergency department was generally consistent
      with the department's mission, but many respondents endorsed a need for a service
      that was not available, such as family therapy. These findings suggest the
      importance of efforts to educate the public about how to obtain mental health
      services.

PMID- 15939954
TI  - Use of mental health services by Asian Americans.
AB  - This study explored the use of mental health services by Asian Americans and
      other ethnic populations (N=104,773) in California. The authors used linear
      regression analyses to assess the role of ethnicity and diagnosis in predicting
      six-month use of services. East Asians used more services than Southeast Asians,
      Filipinos, other Asians, Caucasians, African Americans, Latinos, and Native
      Americans, even when severity of illness was taken into account. The findings
      suggest that aggregating Asian subpopulations into a single group in services
      research is no longer appropriate. Attention needs to be placed on the needs of
      Southeast Asians and other Asians, whose service use patterns approximate those
      of the traditionally most underserved groups, African Americans and Latinos.

PMID- 15939955
TI  - Disparities in use of antipsychotic medications among nursing home residents in
      Arkansas.
AB  - Pilot work was conducted to determine whether there were racial disparities in
      the use of second-generation antipsychotic medications in a sample of 2,717
      residents of nursing homes in Arkansas in 2001. Chi square analysis and a
      logistic regression model were used to examine the relationship between
      residents' race and likelihood of receiving a second-generation antipsychotic.
      Other independent variables included in the model were age, gender, and the
      location of the nursing home. The results indicated racial disparities in use of
      second-generation antipsychotics among the nursing home residents, with African
      American residents less likely to receive these medications than residents from
      other racial or ethnic groups.

PMID- 15939957
TI  - Long-term use of hypnotic agents in the treatment of chronic insomnia.

PMID- 15939959
TI  - Racism and mental illness.

PMID- 15939960
TI  - Service-related needs and opinions of people with schizophrenia in Hungary.

PMID- 15939961
TI  - The BPRS-E as predictor of length of stay in a residential facility.

PMID- 15939963
TI  - Treatment compliance and child custody.

PMID- 15939964
TI  - Profiling of alopecia areata autoantigens based on protein microarray technology.
AB  - Protein biochips have a great potential in future parallel processing of complex
      samples as a research tool and in diagnostics. For the generation of protein
      biochips, highly automated technologies have been developed for cDNA expression
      library production, high throughput protein expression, large scale analysis of
      proteins, and protein microarray generation. Using this technology, we present
      here a strategy to identify potential autoantigens involved in the pathogenesis
      of alopecia areata, an often chronic disease leading to the rapid loss of scalp
      hair. Only little is known about the putative autoantigen(s) involved in this
      process. By combining protein microarray technology with the use of large cDNA
      expression libraries, we profiled the autoantibody repertoire of sera from
      alopecia areata patients against a human protein array consisting of 37,200
      redundant, recombinant human proteins. The data sets obtained from incubations
      with patient sera were compared with control sera from clinically healthy persons
      and to background incubations with anti-human IgG antibodies. From these results,
      a smaller protein subset was generated and subjected to qualitative and
      quantitative validation on highly sensitive protein microarrays to identify novel
      alopecia areata-associated autoantigens. Eight autoantigens were identified by
      protein chip technology and were successfully confirmed by Western blot analysis.
      These autoantigens were arrayed on protein microarrays to generate a disease
      associated protein chip. To confirm the specificity of the results obtained, sera
      from patients with psoriasis or hand and foot eczema as well as skin allergy were
      additionally examined on the disease-associated protein chip. By using alopecia
      areata as a model for an autoimmune disease, our investigations show that the
      protein microarray technology has potential for the identification and evaluation
      of autoantigens as well as in diagnosis such as to differentiate alopecia areata
      from other skin diseases.

PMID- 15939965
TI  - Rabies and the cerebellum: new methods for tracing circuits in the brain.

PMID- 15939966
TI  - Whither neuropsychiatry?

PMID- 15939967
TI  - Toward a neurobiology of psychotherapy: basic science and clinical applications.
AB  - Psychotherapy is used commonly to treat a variety of mental illnesses, yet
      surprisingly little is known about its biological mechanisms especially in
      comparison with pharmacotherapy. In this review we survey the current knowledge
      about changes in brain function following psychotherapeutic intervention that are
      detectable with current neuroimaging techniques. We also consider the possible
      role for neuroimaging in refining clinical diagnoses and predicting treatment
      outcome, which would benefit both clinical decision-making and the cognitive
      neuroscience of psychotherapy.

PMID- 15939968
TI  - Apathy and pituitary disease: it has nothing to do with depression.
AB  - Increasingly, patients with pituitary disease are evaluated and treated at cancer
      centers. In many ways, these patients resemble patients with other malignant
      brain tumors. Although the majority of pituitary adenomas are benign, the
      physical, emotional, and cognitive changes that these patients experience on
      their well-being is malignant. Pituitary disease causes a variety of physical
      illnesses resulting from the alterations in the hypothalamic-pituitary-end organ
      axis. In addition, patients with pituitary diseases may experience many emotional
      problems, including depression, anxiety, behavioral disturbances, and personality
      changes, above and beyond the many reactions these patients may have to the
      myriad of adjustments that they must make in their lives. There is a growing
      understanding that pituitary patients may experience these emotional problems as
      a result of long-term effects that the pituitary tumor itself, treatment, and/or
      hormonal changes have on the hypothalamic-pituitary-end organ axis. The authors
      present a series of cases, in which patients with pituitary disease were
      diagnosed and treated for depression and showed little response to the treatment
      for depression. When the diagnosis of apathy syndrome was considered and
      treatment implemented, the patients' condition improved. A review of the
      literature on apathy, hypothalamic-pituitary-end organ axis dysfunction, and
      treatment for apathy syndrome is included.

PMID- 15939969
TI  - Apathy is associated with volume of the nucleus accumbens in patients infected
      with HIV.
AB  - Apathy refers to a reduction in self-initiated behavior, and it is commonly
      reported by patients infected with human immunodeficiency virus (HIV). It remains
      unclear whether apathy among HIV patients reflects a direct effect of the virus
      on subcortical brain circuits or a secondary neuropsychiatric symptom. In the
      present study we examined the relationship between ratings of apathy and
      quantitative analysis of the nucleus accumbens (NA), a subcortical brain
      structure that regulates initiation of behavioral activation. Twelve HIV-positive
      individuals without dementia were administered the Marin Apathy Scale and
      underwent neuroimaging. Voxel-based quantification of the nucleus accumbens was
      completed using a segmentation protocol. Results of our study revealed that
      increased ratings of apathy were significantly correlated with lower volume of
      the nucleus accumbens. By contrast, ratings of depression were unrelated to
      either apathy or nucleus accumbens volume. These findings provide preliminary
      evidence that apathy reflects direct involvement of the central nervous system in
      patients with HIV.

PMID- 15939971
TI  - The relationship between age and cognitive function in HIV-infected men.
AB  - Several studies have identified increased age as a risk factor for the
      development of cognitive impairment in human immunodeficiency virus (HIV)
      infected subjects, but few have examined the potential synergistic effect of age
      and HIV serostatus on cognitive decline. The authors examined the possible
      combined effect of age and HIV serostatus on cognitive decline in 254 subjects
      stratified by age group and HIV status. After controlling for the effect of
      education, there were significant effects for serostatus and age group on overall
      cognitive impairment and a number of neuropsychological measures but no
      interaction effects. These data suggest that older seropositive individuals are
      not at an increased risk for HIV-related cognitive impairment when normal age
      related cognitive changes are considered.

PMID- 15939970
TI  - Clinical assessment of Axis I psychiatric morbidity in chronic epilepsy: a
      multicenter investigation.
AB  - This study characterizes the rate of current Axis I DSM-IV disorders using a
      brief standardized psychiatric interview procedure, the Mini International
      Neuropsychiatric Interview (v5.0) (MINI), and determined the validity of MINI
      diagnoses of current depressive episodes to the research standard (Structured
      Clinical Interview for DSM-IV Disorders [SCID]). One hundred seventy-four
      patients with chronic epilepsy from five tertiary medical centers were
      interviewed using the MINI and the mood disorders module of the SCID. Current
      Axis I disorders were evident in one-half the sample (49%), with prevalent
      anxiety (30.4%) and mood (21.8%) disorders. Major depressive episode was the most
      common individual diagnosis (17.2%). Concordance was high between the MINI and
      SCID for diagnoses of current depression, especially for major depression. Of
      those with current major depression, less than one-half were treated with
      antidepressant medications. Current Axis I DSM-IV diagnoses can be effectively
      and accurately identified in clinical settings using shorter standardized
      psychiatric interview techniques. Issues regarding recognition and treatment of
      psychiatric morbidity in epilepsy are discussed.

PMID- 15939972
TI  - HIV Dementia Scale and psychomotor slowing--the best methods in screening for
      neuro-AIDS.
AB  - The authors examined the correlation between Human Immunodeficiency Virus (HIV)
      Dementia Scale (HDS) and psychomotor tests, evaluating basal ganglia function in
      266 HIV-seropositive, Caucasian, homosexual men. Fifty-five HIV-positive,
      patients with mild dementia (HDS score < or =10) showed significant slowing of
      most rapid alternating movements (MRAM) and significantly prolonged contraction
      times compared to 211 HIV-positive nondemented patients (HDS score >10). Motor
      performance correlated significantly with the time-dependent HDS subscores for
      psychomotor speed and construction and HDS sum score. In contrast to contraction
      times and MRAM, HDS scores also showed significant correlations to age, premorbid
      and actual intelligence, and duration of HIV seropositivity.

PMID- 15939973
TI  - H215O PET study of impairment of nonverbal recognition with normal aging.
AB  - Little research has been conducted regarding age-related changes in nonverbal
      memory. Using positron emission tomography (PET), the authors studied 17 elderly
      volunteers and 20 young volunteers, during nonverbal recognition task
      performance, to examine differences in brain blood flow. The subjects were asked
      to recognize a study list size (SLS) of shapes that was adjusted so that each
      subject performed at approximately 75% accuracy. Positron emission tomography
      results showed that, relative to younger individuals, elderly subjects engaged
      different regions, including the insula, during recognition. Elderly subjects did
      not show the relationship between parahippocampal flow and SLS, which was
      observed in younger subjects. These differences suggest that age-related
      functional brain changes partly explain performance deficits.

PMID- 15939974
TI  - Behavioral problems in dementia patients and salivary cortisol patterns in
      caregivers.
AB  - This study examines cortisol profiles in caregivers of dementia patients and
      their relationship to patients' behavioral problems. Salivary cortisol profiles
      and cortisol response to awakening were measured in 57 caregivers and 55
      noncaregiver comparison subjects. Caregivers showed significantly higher levels
      of cortisol at the time of morning awakening than did comparison subjects, with a
      smaller increase after awakening. A higher cortisol awakening response was found
      in caregivers of patients with high versus low levels of behavioral and
      psychological symptoms of dementia (BPSD). Elevated morning cortisol levels could
      predispose caregivers to negative health consequences, with caregivers of
      patients with BPSD at greater risk.

PMID- 15939975
TI  - Neuropsychological functioning in early- and late-onset obsessive-compulsive
      disorder.
AB  - Significant relationships have been noted between age of onset and demographics,
      clinical characteristics, and cerebral metabolic activity in obsessive-compulsive
      disorder (OCD). The authors investigated whether patients with early (N=21) and
      late (N=17) onset OCD differ with respect to neuropsychological functioning.
      Results revealed that the late onset OCD group obtained poorer scores on measures
      of executive function and auditory attention than the early onset group. Late
      onset OCD was also associated with poorer visual memory relative to healthy
      comparison subjects. These findings suggest that early and late onset OCD may be
      the result of at least partially differing neurobiological mechanisms.

PMID- 15939976
TI  - Anhedonia, depression, and motor functioning in Parkinson's disease during
      treatment with pramipexole.
AB  - Anhedonia, a core symptom of depression, correlates with motor alterations in
      major depressive disorder and has been assumed to be frequent in depressed
      patients with Parkinson's disease (PD). In the present study, the authors
      assessed for the first time frequency of anhedonia in patients with idiopathic
      Parkinson's disease (N = 657) and the relationship of anhedonia and parkinsonian
      motor deficits during treatment with pramipexole. Mild depression was present in
      47% of the patients and moderate to severe depression in 22%. Anhedonic
      individuals included 45.7% of all patients and 79.7% of depressed Parkinson's
      disease patients. Anhedonic Parkinson's disease patients had greater motor
      deficits, restrictions in activities of daily living, and depression compared to
      nonanhedonic patients. Frequency of anhedonia and depression was significantly
      reduced during treatment with pramipexole. Future studies should further
      investigate antianhedonic efficacy of dopamine agonists including pramipexole in
      depressed patients with Parkinson's disease.

PMID- 15939977
TI  - Tardive dyskinesia predicts prolactin response to buspirone challenge in people
      with schizophrenia.
AB  - Prolactin response to buspirone was evaluated in patients with schizophrenia,
      with and without tardive dyskinesia (TD). Prolactin response in patients with
      schizophrenia without TD was significantly decreased, compared to healthy
      comparison subjects (F = 6.36, df = 5, p < 0.0001). Furthermore, prolactin levels
      after administration of buspirone were not significantly increased from baseline.
      In contrast, there was no prolactin response difference between patients with
      schizophrenia and TD and healthy subjects. This finding suggests that decreased
      dopamine (D(2)) receptor sensitivity may result in lower risk of developing TD
      and may lead to a fuller understanding of the variable expression of D(2)
      receptor mediated side effects.

PMID- 15939978
TI  - Oxidative stress during treatment with first- and second-generation
      antipsychotics.
AB  - Neurotoxicity of first-generation antipsychotics (FGAs) may be involved in lipid
      peroxidation, which is the pathogenesis of extrapyramidal symptoms, including
      tardive dyskinesia (TD). Blood samples at day 0, 7, and 21 drawn from patients
      taking antipsychotics were analyzed for malondialdehyde (MDA) in plasma, a marker
      of lipid peroxidation, by high-performance liquid chromatography. Of 115 patients
      enrolled, 92 patients completed the study. Most MDA levels were within normal
      ranges (<1.0 micromol/liter). Malondialdehyde levels in patients receiving
      clozapine (p = 0.002), quetiapine (p = 0.003), amisulpride (p = 0.008), and
      risperidone (p = 0.008) were significantly lower than within the first generation
      antipsychotic group. The authors conclude that lipid peroxidation is
      significantly higher in treatment with FGAs.

PMID- 15939979
TI  - Adjunctive valproic acid for delirium and/or agitation on a consultation-liaison
      service: a report of six cases.
AB  - The authors present six cases in which valproate was used in patients seen by a
      consultation-liaison service (CLS) to manage delirium and/or psychotic agitation.
      The intravenous (IV) preparation (Depacon, Abbott Laboratories) was used in two
      nothing by mouth (NPO) patients, while the liquid oral preparation (Depakene,
      Abbott Laboratories) was used via nasogastric tube (NGT) in the other patients.
      All of these cases had suboptimal responses and/or concerning side effects from
      conventional therapy with benzodiazepines and/or antipsychotics. In all six
      cases, the CLS use of valproic acid combined with conventional antidelirium
      medications resulted in improved control of behavioral symptoms without
      significant side effects from valproic acid. Consultation-liaison psychiatrists
      should consider the addition of valproic acid to control behavioral symptoms of
      delirium when conventional therapy is inadequate. This may be especially
      advisable when problematic side effects result from more conventional
      psychopharmacological management. Specifically, intravenous valproate sodium may
      be a viable option for NPO patients.

PMID- 15939980
TI  - Relation between estradiol and negative symptoms in men with schizophrenia.
AB  - The authors tested the hypothesis that estradiol would be associated with
      negative symptoms in 30 male schizophrenia inpatients. Medications were switched
      from typical to atypical antipsychotics. Estradiol concentrations were inversely
      correlated with negative symptoms significantly before the switch and at a trend
      level of significance after the switch. Changes in negative symptoms were
      positively correlated with those in estradiol concentrations at a trend level of
      significance. Estradiol could be a biological marker for negative symptoms even
      in male schizophrenia patients.

PMID- 15939981
TI  - Auditory hallucinations after right temporal gyri resection.
AB  - The authors present a case study on the development of auditory hallucinations
      secondary to right temporal lobe damage. Surgical resection in the study patient
      was of the right superficial middle and inferior temporal gyri. Carbamazepine at
      a dosage of 800 mg daily was the most effective medication used. A
      multidisciplinary approach involving the neurosurgeon, psychiatrist, family, and
      rehabilitation specialist is necessary in managing the psychiatric sequelae of
      brain injury.

PMID- 15939982
TI  - Psychopathology in neuropsychiatry: DSM and beyond.
AB  - The case reports described in this article indicate that current neuropsychiatric
      practice is strongly limited by reliance on the Diagnostic and Statistical Manual
      of Mental Disorders (DSM). Knowledge of new psychopathology that will enable the
      neuropsychiatrists and neuroscientists identify specific areas of brain
      dysfunction is essential to modern practice of neuropsychiatry. Today, less than
      20% of neuropsychiatry and neuroscience programs teach such psychopathology.The
      development of brain imaging and metabolic measurement technologies; the
      continuous and rapid introduction of many new pharmaceutical agents into clinical
      care; and the various, detailed editions of the Diagnostic and Statistical Manual
      of Mental Disorders (DSM) have all shaped modern psychiatric training and thus
      future psychiatric practice. This "shaping" is observed most often in the
      teaching of psychopathology and of mental status examinations, both currently
      focusing on how to recognize and elicit the clinical features needed to apply the
      criteria set by the DSM. Once DSM criteria are met, a best-choice treatment plan
      based on DSM diagnosis is selected from an array of pharmacotherapy algorithms.
      It is assumed that the known reliability of the DSM system maximizes the
      likelihood that these diagnostic decisions are valid and treatment choices are
      therefore appropriate. Descriptive psychopathology that goes beyond the DSM is
      primarily relegated to historical consideration and rarely pertains to issues
      regarding patient care.

PMID- 15939983
TI  - Tardive dyskinesia after long-term veralipride treatment.

PMID- 15939984
TI  - Tiagabine for rage, aggression, and anxiety.

PMID- 15939985
TI  - Low-dose-trazodone-induced disorganized type psychosis.

PMID- 15939986
TI  - Obsessive and compulsive symptoms in schizophrenia patients--from neuropsychology
      to clinical typology and classification.

PMID- 15939987
TI  - Persisting dementia after isoniazid overdose.

PMID- 15939988
TI  - Anxiety-induced tremors in a 131/2-year-old female with idiopathic Parkinson's
      disease.

PMID- 15939989
TI  - Acute disseminated encephalomyelitis presenting as conversion disorder.

PMID- 15939990
TI  - Cognitive affective psychosis syndrome in a patient with sporadic
      olivopontocerebellar atrophy.

PMID- 15939991
TI  - Isothermal titration calorimetry.
AB  - Isothermal titration calorimetry is an ideal technique for measuring biological
      binding interactions. It does not rely on the presence of chromophores or
      fluorophores, nor does it require an enzymatic assay. Because the technique
      relies only on the detection of a heat effect upon binding, it can be used to
      measure the binding constant, K, the enthalpy of binding, DeltaH degrees and the
      stoichiometry, or number of binding sites, n. This chapter describes
      instrumentation, experimental design, and the theoretical underpinnings necessary
      to run and analyze a calorimetric binding experiment.

PMID- 15939992
TI  - Direct optical detection of protein-ligand interactions.
AB  - Direct optical detection provides an excellent means to investigate interactions
      of molecules in biological systems. The dynamic equilibria inherent to these
      systems can be described in greater detail by recording the kinetics of a
      biomolecular interaction. Optical biosensors allow direct detection of
      interaction patterns without the need for labeling. An overview covering several
      commercially available biosensors is given, with a focus on instruments based on
      surface plasmon resonance (SPR) and reflectometric interference spectroscopy
      (RIFS). Potential assay formats and experimental design, appropriate controls,
      and calibration procedures, especially when handling low molecular weight
      substances, are discussed. The single steps of an interaction analysis combined
      with practical tips for evaluation, data processing, and interpretation of
      kinetic data are described in detail. In a practical example, a step-by-step
      procedure for the analysis of a low molecular weight compound interaction with
      serum protein, determined on a commercial SPR sensor, is presented.

PMID- 15939993
TI  - Label-free detection of protein-ligand interactions by the quartz crystal
      microbalance.
AB  - In recent years the quartz crystal microbalance (QCM) has been accepted as a
      powerful technique to monitor adsorption processes at interfaces in different
      chemical and biological research areas. In the last decade, the investigation of
      adsorption of biomolecules on functionalized surfaces turned out to be one of the
      paramount applications of the QCM comprising the interaction of nucleic acids,
      specific molecular recognition of protein-receptor couples, and antigen-antibody
      reactions realized in immunosensors. The advantage of the QCM technique is that
      it allows for a label free detection of molecules. This is a result of the fact
      that the frequency response of the quartz resonator is proportional to the
      increase in thickness of the adsorbed layer. However, in recent years it became
      more and more evident that quartz resonators used in fluids are more than mere
      mass or thickness sensors. The sensor response is also influenced by viscoelastic
      properties of the adhered biomaterial, surface charges of adsorbed molecules and
      surface roughness. These phenomena have been used to get new insights in the
      adhesion process of living cells and to understand their response to
      pharmacological substances by determining morphological changes of the cells. In
      this chapter we describe a protocol to explore the kinetics and thermodynamics of
      specific interactions of different proteins such as lectins and annexins with
      their ligands using receptor bearing solid supported lipid bilayers.

PMID- 15939994
TI  - Measurement of solvent accessibility at protein-protein interfaces.
AB  - Methods are presented for monitoring solvent accessibility of protein-ligand and
      protein-protein interfaces. The kinetics of solvent accessibility at the protein
      protein interface is monitored by amide hydrogen/deuterium (H/2H) exchange
      detected by matrix assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry (MS). A straightforward theoretical analysis is presented
      for determining the concentration of a weakly binding ligand that is required for
      achieving a situation in which the receptor is essentially 100% bound, and this
      is verified by control experiments. We show that when the receptor is essentially
      100% bound it is possible to distinguish amide exchange as a result of solvent
      accessibility at the interface from amide exchange caused by complex
      dissociation. Methods are also presented for the measurement of tightly bound
      complexes of large interactions such as antibody-antigen complexes. Quantitation
      of the number of amides sequestered at the interface can be related to the number
      of H2O molecules excluded from the interface.

PMID- 15939995
TI  - Sedimentation velocity method in the analytical ultracentrifuge for the study of
      protein-protein interactions.
AB  - Sedimentation analysis in the analytical ultracentrifuge can be employed to
      detect macromolecular interactions. Whenever two molecules interact the mass of
      the resulting complex is increased and this is reflected in the sedimentation
      behavior. In this chapter we discuss how this phenomenon can be utilized to
      determine quantitative parameters of an interaction. An example, interaction of
      single-stranded DNA binding protein with a subunit of DNA polymerase III
      holoenzyme is given together with a thorough treatment of the relating theory and
      a description of evaluation algorithms.

PMID- 15939996
TI  - Protein-ligand interaction probed by time-resolved crystallography.
AB  - Time-resolved (TR) crystallography is a unique method for determining the
      structures of intermediates in biomolecular reactions. The technique reached its
      mature stage with the development of the powerful third-generation synchrotron X
      ray sources, and the advances in data processing and analysis of time-resolved
      Laue crystallographic data. A time resolution of 100 ps has been achieved and
      relatively small structural changes can be detected even from only partial
      reaction initiation. The remaining challenge facing the application of this
      technique to a broad range of biological systems is to find an efficient and
      rapid, system-specific method for the reaction initiation in the crystal. Other
      frontiers for the technique involve the continued improvement in time resolution
      and further advances in methods for determining intermediate structures and
      reaction mechanisms. The time-resolved technique, combined with trapping methods
      and computational approaches, holds the promise for a complete structure-based
      description of biomolecular reactions.

PMID- 15939997
TI  - X-ray crystallography of protein-ligand interactions.
AB  - Crystal structures of protein-ligand complexes provide a detailed view of their
      spatial arrangement and interactions. In the case of stable, unreactive ligands,
      such as inhibitors or allosteric regulators, the complexes can be generated by
      cocrystallization or by soaking the ligand into fully grown crystals. In order to
      obtain highly occupied stochiometric complexes, the concentration and amount of
      ligand used needs to be considered. Protein complexes with reactive short-lived
      species that occur in chemical or binding reactions can be determined using
      monochromatic X-ray diffraction techniques via kinetic trapping approaches. To
      this end, the kinetics of the reaction has to be determined in the crystalline
      state and triggering methods to start the reaction need to be established. To
      facilitate data interpretation, the experimental conditions are usually chosen
      such that the peak concentration of the reactive species under investigation is
      maximized.

PMID- 15939998
TI  - Combined use of XAFS and crystallography for studying protein-ligand interactions
      in metalloproteins.
AB  - This chapter describes the method of X-ray absorption spectroscopy when applied
      to the study of metal sites in proteins. The method requires the intense X-rays
      found only at synchrotron radiation sources, and is equally applicable to
      metalloproteins in dilute solutions, in fibers, films, and in crystalline states.
      In each case, structural changes occurring at metal sites during catalysis or
      ligand-binding are revealed with an accuracy and precision equivalent to atomic
      resolution crystallography. When combined with crystallographic data, of any
      resolution, X-ray absorption spectroscopy can yield atomic resolution three
      dimensional structural models of the metal sites, thus providing the level of
      structural detail necessary for understanding the chemical mechanisms involved in
      the active states of metalloproteins.

PMID- 15939999
TI  - NMR studies of protein-ligand interactions.
AB  - Interaction between biological macromolecules or of macromolecules with low
      molecular-weight ligands is a central paradigm in the understanding of function
      in biological systems. It is also the major goal in pharmaceutical research to
      find and optimize ligands that modulate the function of biological
      macromolecules. Both technological advances and new methods in the field of
      nuclear magnetic resonance (NMR) have led to the development of several tools by
      which the interaction of proteins or DNA and low molecular weight-ligands can be
      characterized at an atomic level. Information can be gained quickly and easily
      with ligand-based techniques. These need only small amounts of nonisotope
      labeled, and thus readily available target macromolecules. As the focus is on the
      signals stemming only from the ligand, no further NMR information regarding the
      target is needed. Techniques based on the observation of isotopically labeled
      biological macromolecules open the possibility to observe interactions of
      proteins with low-molecular-weight ligands, DNA or other proteins. With these
      techniques, the structure of high-molecular-weight complexes can be determined.
      Here, the resonance signals of the macromolecule must be identified beforehand,
      which can be time consuming but with the benefit of obtaining more information
      with respect to the target ligand complex.

PMID- 15940000
TI  - Probing heme protein-ligand interactions by UV/visible absorption spectroscopy.
AB  - Ultraviolet/visible (UV/vis) absorption spectroscopy is a powerful tool for
      steady-state and time-resolved studies of protein-ligand interactions. Prosthetic
      groups in proteins frequently have strong electronic absorbance bands that depend
      on the oxidation, ligation, and conformation states of the chromophores. They are
      also sensitive to conformational changes of the polypeptide chain into which they
      are embedded. Steady-state absorption spectroscopy provides information on ligand
      binding equilibria, from which the Gibbs free energy differences between the
      ligated and unligated states can be computed. Time-resolved absorption
      spectroscopy allows one to detect short-lived intermediate states that may not
      get populated significantly under equilibrium conditions, but may nevertheless be
      of crucial importance for biological function. Moreover, the energy barriers that
      have to be surmounted in the reaction can be determined. In this chapter, we
      present a number of typical applications of steady-state and ns time-resolved
      UV/vis absorption spectroscopy in the study of ligand binding to the central iron
      in heme proteins.

PMID- 15940001
TI  - Ultrafast time-resolved IR studies of protein-ligand interactions.
AB  - Time-resolved mid-IR spectroscopy combines molecular sensitivity with ultrafast
      capability to incisively probe protein-ligand interactions in model heme
      proteins. Highly conserved residues near the heme binding site fashion a ligand
      docking site that mediates the transport of ligands to and from the binding site.
      We employ polarization anisotropy measurements to probe the orientation and
      orientational distribution of CO when bound to and docked near the active binding
      site, as well as the dynamics of ligand trapping in the primary docking site. In
      addition, we use more conventional transient absorption methods to probe the
      dynamics of ligand escape from this site, as well as the ultrafast dynamics of NO
      geminate recombination with the active binding site. The systems investigated
      include myoglobin, hemoglobin, and microperoxidase.

PMID- 15940002
TI  - Monitoring protein-ligand interactions by time-resolved FTIR difference
      spectroscopy.
AB  - Time-resolved FTIR difference spectroscopy is a valuable tool to monitor the
      dynamics of protein-ligand interactions, which selects out of the background
      absorbance of the whole sample the absorbance bands of the protein groups and of
      the ligands, which are involved in the protein reaction. The absorbance changes
      can be monitored with time-resolutions down to nanoseconds and followed then over
      nine orders of time up to seconds even in membrane proteins with the size of
      100,000 Dalton. Here, we will discuss the various experimental setups. We will
      show new developments for sample cells and how to trigger a reaction within these
      cells. The kinetic analysis of the data will be discussed. A crucial step in the
      data analysis is the clear-cut band assignment to chemical groups of the protein
      and the ligand. This is done either by site directed mutagenesis or by
      isotopically labeling. Examples for band assignments will be presented in this
      chapter.

PMID- 15940003
TI  - Proteins in motion: resonance Raman spectroscopy as a probe of functional
      intermediates.
AB  - Elucidating proteins function at a level that allows for intelligent design and
      manipulation is essential in realization of their potential role in biomedical
      and industrial applications. It has become increasingly apparent though, that
      probing structures and functionalities under equilibrium conditions is not
      sufficient. Rather, many aspects of protein behavior and reactivity are rooted in
      protein dynamics. Thus, there is a growing effort to probe intermediate
      structures that occur transiently during the course of a proteins function in
      particular linked to the binding or release of a ligand or substrate. However,
      studies following the sequence of conformational changes triggered by the binding
      of substrate/ligand and the concomitant change in functional properties are
      inherently difficult because often the diffusion times are of the order of
      conformational relaxation times. This chapter describes methodologies for
      generating resonance Raman spectra from transient forms of hemoglobin under
      conditions that allow for the systematic exploration of conformational relaxation
      and functionality. Special consideration is given to Raman compatible protocols
      based on sol-gel encapsulation that allow for the preparation, trapping and
      temporal tuning of nonequilibrium population generated from either the addition
      or the removal of ligands/substrates.

PMID- 15940004
TI  - Fluorescence polarization/anisotropy approaches to study protein-ligand
      interactions: effects of errors and uncertainties.
AB  - Fluorescence techniques are widely used in the study of protein-ligand
      interactions because of their inherent sensitivity, and the fact that they can be
      implemented at true equilibrium conditions. Fluorescence polarization/anisotropy
      methodologies, in particular, are now extensively utilized in biotechnology and
      clinical chemistry. In this chapter, we shall discuss both theoretical and
      practical aspects of polarization/anisotropy methods. We shall also focus
      attention on considerations of errors and uncertainties in such measurements, and
      how these uncertainties affect the ultimate estimation of ligand-protein
      dissociation constants.

PMID- 15940005
TI  - Ligand binding with stopped-flow rapid mixing.
AB  - Stopped-flow rapid mixing is a common, direct technique for the study of ligand
      binding reactions. In this method, protein and ligand are mixed together at
      relatively high velocities directly into an observation chamber, so that time
      courses for reactions occurring on time scales as short as a few milliseconds can
      be measured. This chapter presents an introduction to this technique, including a
      discussion of experimental and technical issues that must be addressed when
      designing stopped-flow experiments. Simple experiments for measuring reaction
      dead time and flushing volume are also described along with the details of
      several common reaction schemes and methods for data analysis.

PMID- 15940006
TI  - Circular dichroism spectroscopy for the study of protein-ligand interactions.
AB  - Circular dichroism (CD) is the difference in absorption of left and right
      circularly polarized light, usually by a solution containing the molecules of
      interest. A signal is only measured for chiral molecules such as proteins. A CD
      spectrum provides information about the bonds and structures responsible for this
      chirality. When a small molecule (or ligand) binds to a protein, it acquires an
      induced CD (ICD) spectrum through chiral perturbation to its structure or
      electron rearrangements. The wavelengths of this ICD are determined by the
      ligand's own absorption spectrum, and the intensity of the ICD spectrum is
      determined by the strength and geometry of its interaction with the protein.
      Thus, ICD can be used to probe the binding of ligands to proteins. This chapter
      outlines protein CD and ICD, together with some of the issues relating to
      experimental design and implementation.

PMID- 15940007
TI  - High-throughput screening of interactions between G protein-coupled receptors and
      ligands using confocal optics microscopy.
AB  - Interactions of extracellular ligands with proteins in the cellular plasma
      membrane are the starting point for various intracellular signaling cascades. In
      the pharmaceutical industry, particular attention has been paid to G protein-
      coupled receptors (GPCRs), which are involved in various disease processes. In so
      called high-throughput screening (HTS) campaigns, large medicinal chemistry
      compound libraries were searched for bioactive molecules that would either induce
      or inhibit the activity of a specific disease-relevant GPCR. In the respective
      drug discovery assays, the test compound typically competes with the
      physiological ligand for a binding site on the receptor. The transmembrane
      receptor is prepared in the form of membrane fragments or, as described here, in
      so-called virus-like particles (VLiPs). As hundreds of thousands of test
      compounds must be analyzed, there is a strict need for low volume binding assays
      to save the expensive bioreagents, and to reduce the consumption of the test
      compounds. In this chapter, we describe the application of confocal optics
      microscopy to measure GPCR ligand interactions in low microliter assay volumes.

PMID- 15940008
TI  - Single-molecule study of protein-protein and protein-DNA interaction dynamics.
AB  - Protein-protein and protein-DNA interactions play critical roles in biological
      systems, and these interactions often involve complex mechanisms and
      inhomogeneous dynamics. Single-molecule spectroscopy is a powerful and
      complimentary approach to decipher such spatially and temporally inhomogeneous
      protein interaction systems, providing new information that are not obtainable
      from static structure analyses, thermodynamics characterization, and ensemble
      averaged measurements. To illustrate the single-molecule spectroscopy and imaging
      technology and their applications on studying protein-ligand interactions, this
      chapter focuses on discussing two recent single-molecule spectroscopy studies on
      protein-protein interaction in cell signaling process and on protein-DNA
      interactions in DNA damage recognition process.

PMID- 15940009
TI  - Application of fluorescence correlation spectroscopy to hapten-antibody binding.
AB  - Two-photon fluorescence correlation spectroscopy 2P-FCS has received a large
      amount of attention over the past ten years as a technique that can monitor the
      concentration, the dynamics, and the interactions of molecules with single
      molecule sensitivity. In this chapter, we explain how 2P-FCS is carried out for a
      specific ligand-binding problem. We briefly outline considerations for proper
      instrument design and instrument calibration. General theory of autocorrelation
      analysis is explained and straightforward equations are given to analyze simple
      binding data. Specific concerns in the analytical methods related to IgG, such as
      the presence of two equivalent sites and fractional quenching of the bound hapten
      fluorophore conjugate, are explored and equations are described to account for
      these issues. We apply these equations to data on two antibody-hapten pairs:
      antidigoxin IgG with fluorescein-digoxin and antidigitoxin IgG with Alexa488
      digitoxin. Digoxin and digitoxin are important cardio glycoside drugs, toxic at
      higher levels, and their blood concentrations must be monitored carefully.
      Clearly, concentration assays based on IgG rely on accurate knowledge of the
      hapten-IgG binding strengths. The protocols for measuring and determining the
      dissociation constants for both IgG-hapten pairs are outlined and discussed.

PMID- 15940010
TI  - Atomic force microscopy measurements of protein-ligand interactions on living
      cells.
AB  - Cell adhesion receptors are expressed on the surface of cells and can mediate
      binding to other cells and to the extracellular matrix. Here, we describe in
      detail the use of atomic force microscopy (AFM)-based force spectroscopy for
      studying cell detachment forces on living leukocytes. With this technique it is
      now possible to measure force with resolution down to the level of individual
      molecules. AFM force spectroscopy is particularly well suited for research in
      cell adhesion, which has relevance in both the medical and life sciences
      including immunology, cancer and stem cell research, and human pharmacology.
      Along with its limitations, we herein, describe how the rupture force of a single
      complex formed between the integrin receptor leukocyte function-associated
      antigen (LFA)-1, expressed on the surface of a living leukocyte, and immobilized
      intercellular adhesion molecule-1 (ICAM-1) was measured. With only minor
      modifications this protocol can be used to study other adhesion receptors on
      almost any mammalian cell or bacterial system. This protocol is also suitable for
      studying single-molecule de-adhesion events in cell-free systems as well as
      between two living cells.

PMID- 15940011
TI  - Computer simulation of protein-ligand interactions: challenges and applications.
AB  - The accurate modeling of protein-ligand interactions, like any prediction of
      macromolecular structure, requires an energy function of sufficient detail to
      account for all relevant interactions and a conformational search method that can
      reliably find the energetically favorable conformations of a heterogeneous
      system. Both of these prerequisites represent daunting challenges. Consequently,
      the routine docking of small molecules or peptides to proteins in their correct
      binding modes, and the reliable ranking of binding affinities remain unsolved
      problems. Nonetheless, computational techniques are continually evolving so as to
      broaden the range of feasible applications, and the accuracy of predictions and
      theoretical approaches can often be of great help in guiding and interpreting
      experiments. We discuss the energetics of protein-ligand systems and survey
      conformational searching techniques. We illustrate how molecular modeling of a
      protein-ligand complex sheds light on the observed resistance of a mutant
      dihydrofolate reductase to the antibiotic trimethoprim. In another example, we
      show that relaxation of side chains in different crystal structures of the same
      complex, benzamidine bound to trypsin, is needed to draw sensible conclusions
      from the calculations. The results of these relatively simple conformational
      searches underscore the importance of incorporating protein flexibility in
      simulations of protein-ligand interactions, even in the context of relatively
      rigid binding pockets.

PMID- 15940012
TI  - Study of ligand-protein interactions by means of density functional theory and
      first-principles molecular dynamics.
AB  - Density Functional Theory (DFT) is a promising technique to study protein-ligand
      interactions from an atomistic-electronic point of view. It provides information
      on the electronic rearrangements upon ligand binding, the structure and the
      relative energy of the ligand in the binding pocket, among other properties. In
      addition, DFT-based techniques such as first-principles molecular dynamics (FPMD)
      (e.g., the Car-Parrinello [CP] method) are used to simulate the short-time
      dynamics of ligand-protein interactions. These techniques are emerging as a
      useful tool to decipher complex protein-ligand interactions in which chemical
      bonds are formed and/or broken during the binding process. In this chapter, the
      basis of DFT, its limitations, and current developments of the theory are
      discussed, focusing on its applications in the area of ligand-protein
      interactions. The performance of the method is illustrated with three examples in
      which the ligand binding process induces changes in the spin state or in the
      protonation state of the active species. The first two examples deal with the
      binding of oxygen to the active center of myoglobin, whereas the third one
      describes the binding of a formic acid inhibitor in the active center of
      catalase.

PMID- 15940013
TI  - Aggregation of mitochondria.

PMID- 15940014
TI  - Recent advances in interventional radiology for acute massive pulmonary
      thromboembolism.
AB  - Acute massive pulmonary thromboembolism is life-threatening and requires vigorous
      treatment. Anticoagulation is the most traditional treatment for pulmonary
      thromboembolism, but may not be sufficient for massive thromboemboli. Systemic
      thrombolytic therapy and surgical thrombectomy are the traditional therapeutic
      options in this situation. Catheter-directed thrombolysis, percutaneous
      embolectomy and, more recently, percutaneous thrombus fragmentation techniques
      using specialized devices are now available to treat the most severe cases of
      massive pulmonary thromboembolism. The success of these techniques depends on a
      thorough understanding of the mechanism of action of each of the devices and
      familiarity with the relevant catheterization techniques. We present a review of
      currently available equipment and techniques, and describe our work with hybrid
      treatment using a combination of mechanical fragmentation, localized fibrinolysis
      and clot aspiration.

PMID- 15940015
TI  - Neonatal encephalopathy and cerebral palsy.

PMID- 15940016
TI  - Luteinizing hormone-releasing hormone agonist monotherapy for prostate cancer:
      outcome and prognostic factors.
AB  - BACKGROUND: We assessed the outcome and prognostic factors in men with prostate
      cancer after luteinizing hormone-releasing hormone agonist monotherapy. METHODS:
      Between April 1998 and August 2002, 62 men with prostate cancer who were treated
      with monotherapy at our institution were included in this analysis. Prostate
      specific antigen (PSA) failure-free (bNED) survival was calculated using Kaplan
      Meier methods. Prognostic factors were evaluated using Cox proportional hazards
      regression model. RESULTS: We reviewed the data of patients, with a median follow
      up from the commencement of monotherapy of 26 months. The overall survival rate
      at 3 years was 89.9%. The bNED survival rate was 63.7% at 3 years. Of the 20
      patients with clinical stage B, 2 progressed to PSA failure, whereas PSA failure
      was seen in 8 of 30 patients with stage C and 8 of 12 patients with stage D. The
      significant factors for bNED status were an initial PSA level of <30 ng/ml
      (p=0.0044), achievement of PSA nadir level of <2.0 ng/ml (p<0.001), and Gleason
      score of <or=6 (p<0.001). CONCLUSIONS: Patients with high clinical stage, a high
      initial PSA level of >or=30 ng/ml, and high Gleason score of >or=7 are at
      increased risk for PSA failure. Failure to achieve PSA nadir level of <2.0 ng/ml
      is an important predictor of the progression. The use of PSA nadir can provide
      useful guidelines for the reconsideration of treatment in patients who have
      received monotherapy.

PMID- 15940017
TI  - Evaluation of the changes in the muscle sympathetic nerve activity and anterior
      tibial muscle blood flow caused by the Valsalva maneuver in patients with lumbago
      and healthy subjects.
AB  - Clinical symptoms affecting the lower extremities are common among lumber spinal
      disorder patients. Pain, numbness and sensory disturbance are major signs of
      these symptoms, and have been suggested to be related to sympathetic nerve
      disturbance. This study was designed to examine whether these patients experience
      a difference in sympathetic nerve flow in terms of muscle sympathetic nerve
      activity (MSA) compared to healthy subjects. Five patients with lumbar
      intervertebral disc herniation of the spine (LIDH) and four patients with lumbar
      spinal canal stenosis (LSCS) were examined along with six healthy volunteers.
      Basic MSAs for IDH and SCS patients that were introduced from a common peroneal
      nerve were found to be statistically higher than those of the control subjects.
      MSA behavior and muscle blood flow introduced from the tibialis anterior muscle
      over 30 seconds while performing the Valsalva maneuver, a well-known technique
      used to artificially facilitate MSA, were examined for all subjects, and showed
      relatively slower changes for LIDH and LSCS patients compared to the normal
      subjects. Muscle blood flow was inversely proportional to MSA for the normal
      subjects, and this relationship was observed for IDH patients as well as SCS
      patients. However, MSA and the muscle blood flow of patients gradually changed
      while performing the Valsalva maneuver relative to the control subjects. This
      suggests that the systemic physiological response to the maneuver is maintained,
      but that, some local modification mechanisms exist.

PMID- 15940018
TI  - Temporalis muscle-galea pedicled flap for reconstruction of longstanding facial
      paralysis.
AB  - Reanimation of longstanding facial paralysis is a difficult clinical problem
      commonly tackled with the method of pedicled muscle flap transfer. The temporalis
      muscle has been the most popular. In the past, one common problem was that the
      flap was not long enough to reach parts of the face distant from the affected
      area. To overcome this disadvantage, we have devised a flap consisting of the
      pedicled temporalis muscle, temporal fascia and galea together and have achieved
      good static results in paralyzed faces. From June, 1996 to May, 2003, we used
      this procedure with 38 longstanding facial paralysis patients (16 male and 22
      female); 23 had right-sided and 15 had left-sided facial paralysis. The patients
      were followed-up over three years. Our results were recorded as "Excellent",
      "Good", "Fair" or "Poor". Excellent or good results were obtained in 33 patients
      (87%). In these patients, the static results are very good. The oral commissure
      on the affected side maintained a favorable position and almost complete symmetry
      of expression was attained. We have achieved dynamic reconstruction by using a
      temporalis muscle-galea pedicled flap in 38 longstanding facial paralysis
      patients. Our results show that this is a good option in treating such patients.

PMID- 15940019
TI  - Hirschsprung's disease in adults: report of a case and review of the literature.
AB  - Hirschsprung's disease in the adult is a rare and frequently misdiagnosed cause
      of long-standing refractory constipation. We report a case of Hirschsprung's
      disease in a 23-year-old man and review the literature. The patient had a history
      of chronic constipation that required daily enemas, since early infancy, but he
      had remained in good health until intestinal obstruction developed. As a
      subemergency operation, right transverse colostomy was performed, to relieve the
      constipation. Histological examination, by a biopsy, showed absence of ganglion
      cells in the myenteric plexus in the rectum. One year later, Ikeda's modification
      of the Duhamel procedure was successfully performed as definitive surgery. The
      postoperative course was uneventful, and complete resolution of the symptoms
      without complications has been confirmed by a 22-year follow-up. A review of 229
      cases of adult Hirschsprung's disease in the literature suggested that the
      Duhamel procedure is the operation of choice because of the lower postoperative
      morbidity rate and better functional outcome.

PMID- 15940020
TI  - Inflammatory pseudotumor in the Spiegel lobe of the liver of an elderly woman.
AB  - We describe an inflammatory tumor in the Spiegel lobe of the liver of an 81-year
      old woman. The patient was referred to our hospital for evaluation of a fever of
      over 39 degrees C and upper abdominal pain. Both conditions had persisted for
      five days in spite of antibiotic treatment. Initial laboratory tests revealed a
      serum C-reactive protein concentration of 20.9 mg/dL and white blood cell count
      of 15,500/microL. Abdominal ultrasound showed a hypoechoic lesion measuring 4 cm
      in diameter in the Spiegel lobe of the liver. A follow-up abdominal ultrasound
      revealed that the hypoechoic lesion was not decreased in size. Computed
      tomography showed a moderate-to-high-density area in the arterial phase and a low
      density area in the Spiegel lobe on delayed phase. Magnetic resonance imaging
      showed a faint low-intensity lesion on T1-weighted imaging and moderate-to-high
      intensity lesion on T2-weighted imaging in the Spiegel lobe. Angiography showed a
      slight hypervascularity in the area of the Spiegel lobe. Antibiotics and nu
      globulin were commenced soon after admission and the fever gradually improved.
      Ultrasound-guided liver biopsy revealed that the hepatic parenchyma was almost
      completely replaced by dense hyalinized fibrous tissue and inflammatory cells.
      These findings were construed to indicate a benign lesion, but the tumor remained
      unchanged. Malignant disease could not be completely ruled out. Segment 1 of the
      liver was resected. Macroscopic examination of the resected specimen revealed a
      gray, fibrotic, solid tumor. The border of the tumor was well-circumscribed but
      not encapsulated. Microscopically, the tumor showed a marked fibrotic background
      with infiltration by a mixed population of lymphocytes, plasma cells,
      histiocytes, and reactive, plump spindle cells. The postoperative course was
      uneventful. The patient has remained well in the 10 months since the resection
      without recurrence.

PMID- 15940021
TI  - Maternal treatment with MCI-186 does not improve delayed deterioration of
      cellular bioenergetic state and mitochondrial activity following transient
      intrauterine ischemia in the fetal rat brain.
AB  - The mitochondrial respiratory activities and energy metabolism in the fetal rat
      brain were measured at the end of 30 minutes of intrauterine ischemia and after 2
      and 4 hours of recirculation. The transient ischemia was associated with a
      delayed deterioration of cellular bioenergetic state and mitochondrial
      activities. The deterioration was not prevented by a free radical scavenger, 3
      methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), given immediately after
      recirculation.

PMID- 15940022
TI  - The use of a writing group to enhance voice and connection among staff nurses.
AB  - The aim of this study was to pilot test a group-writing intervention to decrease
      negative workplace behaviors. The pilot test demonstrated that cohesive and
      supportive relationships developed and allowed nurses to talk about important
      topics. The participants suggested that a writing group would be a forum that
      could be used by staff development educators to encourage nurses to support each
      other and develop their voices.

PMID- 15940024
TI  - Preparation and care at the time of death: content of the ELNEC curriculum and
      teaching strategies.
AB  - Nurses are exposed to death across the lifespan ranging from stillbirths to
      neonatal deaths to deaths of children, adolescents, or adults from trauma or
      various acute or chronic illnesses. To provide quality care at the end of life,
      nurses must not only possess the knowledge and skills to provide effective end-of
      life care, but must also develop the attitudes and interpersonal competence to
      provide compassionate care. The purpose of this article is to present the key
      content and teaching strategies related to preparation and care at the time of
      death based on the End-of-Life Nursing Education Consortium (ELNEC) curriculum.
      As nurses are educated regarding end-of-life care in undergraduate nursing
      curriculums and through continuing education programs, the expectation is that
      quality care will be provided and the suffering of patients and families
      alleviated. Clearly, nurses play a key role in improving the care of the dying in
      America.

PMID- 15940026
TI  - Learning communities: the link to recruitment and retention.
AB  - The professional learning community is a strategy to help staff development
      educators address recruitment and retention and organizational culture. The
      purpose of this article is to analyze the concept of learning communities and
      discuss their potential to increase the recruitment and retention of new graduate
      nurses and returning practitioners to the nursing profession. Incorporating
      learning communities into the healthcare organization will decrease the number of
      nurses leaving nursing, foster retention, and thus, enhance recruitment.

PMID- 15940027
TI  - Nurturing the seeds of learning: a professional development initiative for
      hospital-based nurse educators.
AB  - This article describes a collaborative initiative between two healthcare
      organizations to promote professional development of nurse educators from
      hospitals in neighboring regions. Information collected from a needs survey and a
      preregistration questionnaire was used to develop didactic and interactive
      sessions of a 1-day conference. Several brainstorming sessions were utilized to
      engage participants and to facilitate networking. Participants responded
      positively to this professional development conference in meeting their learning
      needs.

PMID- 15940028
TI  - Creation of a stepdown nurse internship program.
AB  - Within Christiana Care Health System, an opportunity evolved to develop a nurse
      recruitment strategy for our stepdown units. Being a large teaching system, there
      was specific need for nursing education at this entry level. Through
      collaboration of nursing colleagues, the Stepdown Nurse Internship Program was
      created. The program encompassed clinical orientation and didactic classes. Of
      notable significance at the completion of the program were the Basic Knowledge
      Assessment Test score improvement and the nurse retention rate.

PMID- 15940029
TI  - Mentor training in a military nurse corps.
AB  - Mentoring relationships benefit the mentor, protege, and the organization.
      Although the Air Force, Army, and Navy Nurse Corps recognize the importance and
      potential of such relationships, formal methods to develop and support new
      mentors have not been widely adopted. A brief literature review of mentoring
      relationships, followed by a description of the uniqueness of military nursing,
      and finally, the details of development, implementation, and suggestions for
      evaluation of a formal mentor training workshop are presented. The military
      experience can also provide parallels for civilian organizations facing
      recruitment and retention issues, particularly those with multiple sites.

PMID- 15940030
TI  - Pediatric code readiness: practice is the key.
AB  - Nurses caring for children in an acute care setting may be faced with a pediatric
      emergency. Being prepared is essential. This article describes the development of
      a program that gives nurses the opportunity to transfer their knowledge and skill
      into practice. Nurses who participate in this program report feeling more
      confident to provide lifesaving measures.

PMID- 15940032
TI  - Tacrolimus and posttransplant diabetes mellitus in renal transplantation.
AB  - The most prominent side effect of tacrolimus is the induction of posttransplant
      diabetes mellitus (PTDM). In this review, the authors discuss the incidence,
      mechanism, prevention, and treatment of tacrolimus-induced PTDM in renal
      patients.

PMID- 15940033
TI  - Altruistic living kidney donation challenges psychosocial research and policy: a
      response to previous articles.
AB  - BACKGROUND: Policies with respect to altruistic living kidney donation to
      strangers (both nondirected and directed donation) should, in addition to medical
      criteria, preferably be based on valid attitude research data. However, deciding
      on what data are relevant is a normative issue. The challenge for both research
      and policy making is to bring together empirical and normative issues. METHODS:
      By comparing two recent surveys, the authors shed light on the complex
      methodologic and ethical questions surrounding altruistic living kidney donation.
      RESULTS: The authors found that the main methodologic issues were the distinction
      between the willingness to donate and the acceptability of the offer, the
      difference between public attitudes observed in surveys ("facts") and well
      considered moral judgments ("norms"), and biases caused by a misperception of
      central moral concepts (e.g., discrimination and injustice). The authors argue
      that transplantation centers have a good case for applying or initiating
      altruistic living donation programs. Centers should seek to influence public
      attitudes if these attitudes are shown to be biased by prejudice and
      misunderstanding. CONCLUSIONS: The authors advocate an interaction between
      research and policy making. Social research can best influence transplantation
      policies in altruistic living donation by in-depth interviews into the
      complicated background beliefs underlying personal preferences. In addition, the
      public should be encouraged to judge the immanent issues in a morally responsible
      way. In the end, a fair balance should be established between the impartial
      requirements of social justice and the partial motivations of individuals
      involved in altruistic living donation. Although discriminatory acts should be
      rejected categorically, donation policies should be willing to consider, support,
      and accept motivations based on personal loyalties.

PMID- 15940034
TI  - Tailoring a homeostatic expansion to favor donor hematopoiesis.

PMID- 15940035
TI  - Pharmacodynamics of oral ganciclovir and valganciclovir in solid organ transplant
      recipients.
AB  - BACKGROUND: A randomized, double-blind study was conducted to evaluate the
      pharmacokinetics of ganciclovir following oral administration of ganciclovir or
      valganciclovir for prophylaxis of cytomegalovirus (CMV) disease in solid organ
      transplant recipients (n = 240/372). METHODS: The correlations between individual
      exposure to ganciclovir during prophylaxis, with CMV viremia incidence during and
      after treatment, CMV disease up to 12 months posttransplant, and hematological
      toxicity were assessed. RESULTS: Mean daily areas under the curve (AUCs) of
      ganciclovir from valganciclovir and oral ganciclovir were 46.3 +/- 15.2 and 28.0
      +/- 10.9 microg.h/ml (mean +/- SD), respectively. Viremia was suppressed during
      prophylaxis when exposure to ganciclovir was 40-50 microg.h/ml, AUCs typical of
      those achieved in valganciclovir-treated patients. The development of viremia 1
      month after ending prophylaxis was also reduced with higher ganciclovir AUC
      (median predicted incidence, 20% and 10% at AUCs of 33 and 50 microg h/ml,
      respectively). The development of CMV disease within 1 year of transplant was
      17.6% and independent of prophylactic exposure to ganciclovir. There was only a
      weak tendency to increased neutropenia and leukopenia with higher ganciclovir
      exposure. CONCLUSIONS: The greater systemic exposure to ganciclovir delivered by
      valganciclovir was associated with delayed development of viremia. There was only
      a weak association between AUC and hematological toxicity.

PMID- 15940036
TI  - Engraftment of allogeneic hematopoietic stem cells requires both inhibition of
      host-versus-graft responses and 'space' for homeostatic expansion.
AB  - BACKGROUND: The establishment of host-versus-graft (HvG) tolerance is the primary
      aim of reduced intensity conditioning (RIC) regimens for allogeneic stem cell
      transplantation (SCT). It remains to be clarified to what extent recipient
      myeloablation is fundamental in the establishment of donor chimerism. METHODS: We
      have addressed this question in a murine model of RIC SCT in which the donor
      recipient combination produces HvG against the male specific minor
      histocompatibility antigen HY. In this system engraftment can be monitored by RT
      PCR and HvG effectors enumerated by tetramer analysis. RESULTS: We demonstrate
      that the dose of irradiation influences donor hemopoietic engraftment and affects
      generation of anti-donor specific T cells. Chimeric recipients do not mount a HvG
      immune response, becoming selectively tolerant, as demonstrated by the long term
      acceptance of skin grafts of donor but not third party origin. However, HvG
      tolerance is not sufficient to secure engraftment since, even in the absence of
      HvG, partial myeloablation was still required. The "space" produced by
      myeloablation and the consequent potential for donor cell expansion could also
      affect HvG tolerance, since its induction is severely impaired when donor
      hematopoietic cells have reduced proliferative capacity. CONCLUSIONS: We conclude
      that both some degree of myeloablation and HvG tolerance are required for
      successful engraftment, and that the capacity of donor cells to proliferate
      influences the induction of HvG tolerance.

PMID- 15940037
TI  - Tolerance to rat heart grafts induced by intrathymic immunomodulation is mediated
      by indirect recognition primed CD4+CD25+ Treg cells.
AB  - BACKGROUND: In a rat model (PVG.R8-to-PVG.1U) disparate for one class I antigen,
      RT.1Aa, we previously demonstrated that intrathymic immunomodulation with donor
      antigens resulted in prolonged survival of cardiac allografts that underwent
      chronic rejection. However, long-term survivors developed a regulatory cell
      population that prevented both acute and chronic rejection when adoptively
      transferred into secondary graft recipients. The purpose of this study was to
      characterize these regulatory cells with particular emphasis on CD4+CD25+ Treg
      cells. METHODS: Spleens, lymph nodes, and peripheral blood lymphocytes of
      secondary tolerant recipients were characterized using antibodies to various T
      cell markers in flow cytometry. In vitro MLR and in vivo adoptive transfer
      experiments were conducted to investigate the involvement of CD4+CD25+ T cells in
      the observed tolerance. The presence of various cytokines in the sera of graft
      recipients and MLR culture supernatants was tested using ELISA. RESULTS: Tolerant
      recipients compared with naive rats had substantially higher percentages of
      CD4+CD25+ T cells in the spleen (28+/-3% vs. 11+/-5%) and blood (23+/-6% vs. 9+/
      4%). Tolerant animals also had higher levels of serum IL-10 than naive and
      rejecting animals. CD4+CD25+ T cells from secondary long-term graft survivors
      inhibited donor-specific proliferative responses in vitro that was associated
      with high IL-10 production. Importantly, depletion of CD4+CD25+ T cells from
      splenocytes of tolerant rats abrogated their ability to transfer tolerance to
      tertiary graft recipients. CONCLUSIONS: Our data demonstrate that cardiac
      allograft tolerance in this model is mediated by CD4+CD25+ Treg cells primed by
      indirect recognition and is associated with high levels of IL-10.

PMID- 15940038
TI  - Association of circulating interleukin (IL)-12- and IL-10-producing dendritic
      cells with time posttransplant, dose of immunosuppression, and plasma cytokines
      in renal-transplant recipients.
AB  - BACKGROUND: Interleukin (IL)-12-producing dendritic cells (IL-12+DC) polarize T
      helper (Th) differentiation toward Th1, whereas IL-10+DC induce Th
      differentiation toward Th2. We investigated DC and plasma cytokine patterns early
      and late after transplantation. METHODS: Twenty-five hospitalized renal
      transplant recipients without acute rejection or infection early (<40 days)
      posttransplant, 32 symptom-free outpatients with long-term functioning
      transplants (2,762+/-2,423 days posttransplant), and 17 healthy controls were
      studied. The intracellular production of IL-12 and IL-10 in CD11c+ CD83+ CD40+ DC
      was measured in freshly obtained whole blood using four-color fluorescence flow
      cytometry. In addition, plasma cytokine levels were investigated. RESULTS: Early
      and late posttransplant patients had significantly lower proportions of IL-12+DC
      (early: P=0.001; late: P=0.034) and lower ratios of IL-12+/IL-10+DC (early:
      P=0.0001; late: P<0.0001) than healthy controls. IL-10+DC (P=0.0004) and IL-12+DC
      (P=0.002) increased with time posttransplant in association with dose reductions
      of cyclosporine (IL-10+DC: P=0.003; IL-12+DC: P=0.005), methylprednisolone (IL
      10+DC: P<0.0001; IL-12+DC: P=0.001) and mycophenolate mofetil (IL-10+DC:
      P<0.0001; IL-12+DC: P=0.004). Both IL-10+DC and IL-12+DC were associated with low
      plasma IL-10 (IL-10+DC: P=0.010; IL-12+DC: P=0.011) and high plasma IL-6 (IL
      10+DC: P=0.001; IL-12+DC: P=0.009). IL-10+DC were also associated with high
      plasma levels of IL-3 (P=0.003), interferon (IFN)-gamma (P=0.014), and IL-2
      (P=0.058). CONCLUSION: IL-10+DC and IL-12+DC in peripheral blood are associated
      with time after transplantation and dosage of immunosuppression. IL-10+DC
      dominate late posttransplant in the presence of Th1 plasma cytokines (high IFN
      gamma and IL-2), high IL-3, and low IL-10. These findings could be a reflection
      of immunoregulatory processes favoring long-term allograft acceptance.

PMID- 15940039
TI  - Polyclonal rabbit antithymocyte globulin triggers B-cell and plasma cell
      apoptosis by multiple pathways.
AB  - BACKGROUND: Polyclonal antithymocyte globulin (ATG) is widely used as an anti-T
      cell agent for induction and treatment of acute cellular rejection in solid organ
      transplantation. The authors recently demonstrated that rabbit (r) ATG can be
      used in combination with plasmapheresis to effectively treat antibody-mediated
      renal allograft rejection. This observation suggested that rATG may have anti-B
      cell activity. METHODS: The authors tested the complement-independent, apoptosis
      inducing properties of rATG on CD27- naive B cells, CD40 ligand-activated B
      cells, and plasma cells in vitro by annexin V staining, subdiploid DNA content,
      caspase activation, and loss of mitochondrial membrane polarity. Potential
      surface targets for rATG were assayed by competitive inhibition of monoclonal
      antibody binding. RESULTS: Rabbit ATG strongly induced apoptosis in vitro against
      naive, activated B cells and bone marrow resident plasma cells at clinically
      relevant concentrations (1-100 ng/mL). The authors found rATG activity against
      numerous B-cell surface proteins and observed that crosslinking of CD30, CD38,
      CD95, CD80, and HLA-DR likely accounts for this activity. F(ab)2 fragments of
      rATG showed 90% of the activity of the intact molecule, suggesting participation
      of the Fc fragment. Inhibition of caspase- and cathepsin-dependent apoptotic
      pathways partially inhibits rATG-induced B-cell apoptosis. Immunohistochemical
      staining of pediatric thymi demonstrated the presence of CD20+ B cells and CD138+
      plasma cells within the thymic parenchyma, which accounts for the anti-B-cell
      activity in rATG. CONCLUSIONS: Polyclonal rATG induces complement-independent
      apoptosis of naive, activated, and plasma B cells. This effect appears to involve
      the caspase- and cathepsin-mediated apoptosis pathways.

PMID- 15940040
TI  - Superiority of the two-layer method before islet isolation confirmed by in vivo
      viability assessment.
AB  - BACKGROUND: Although the outcome of islet transplantation has improved, there
      remains a major obstacle in isolating viable islets from prolonged preserved
      pancreas. We previously reported that the two-layer cold storage method (TLM)
      improved the yield and in vitro function. In this study, we performed in vivo
      accurate functional analyses of islets from TLM-preserved pancreas and
      investigated pancreatic duct cell viability, which may critically affect islet
      isolation. METHODS: Rat islets isolated from fresh pancreas (group 1), after
      preservation in the University of Wisconsin (UW) solution (group 2) or by the TLM
      (group 3), were examined by assessing islet yields, stimulation indices, cure
      rates after transplantation to diabetic nude mice, and trypan blue uptake of
      pancreatic duct cells. RESULTS: TLM significantly improved the islet yield
      compared with UW cold storage. The cure rates after transplantation were 100%,
      0%, and 80% for groups 1, 2, and 3, respectively. This indicates that islet
      viability was well maintained even after 24 hr of TLM preservation. The
      percentages of nonviable duct cells were 4.1%+/-1.9%, 48.3%+/-8.0%, and 26.1%+/
      21.4% in groups 1, 2, and 3, respectively, showing that the TLM was superior to
      UW as seen by this duct cell viability assessment. CONCLUSIONS: The TLM used for
      pancreas preservation before islet isolation results in excellent islet function
      in addition to improved islet yield comparable to freshly isolated islets. The
      underlying mechanism may be duct cell viability maintained during TLM
      preservation. Therefore the TLM is an excellent preservation technique for
      isolating sufficient numbers of highly viable islets.

PMID- 15940041
TI  - Combined effects of losartan and pravastatin on interstitial inflammation and
      fibrosis in chronic cyclosporine-induced nephropathy.
AB  - BACKGROUND: Statins and angiotensin II type I receptor blockers have synergistic
      effects on vascular smooth-muscle-cell proliferation and the progression of renal
      diseases. We evaluated whether combined treatment with losartan (LSRT) and
      pravastatin (PRVT) affords superior protection compared with their respective
      monotherapies in treating chronic cyclosporine (CsA)-induced nephropathy in rats.
      METHODS: Rats maintained on a low salt diet were given vehicle, CsA (15 mg/kg),
      CsA and LSRT (10 mg/kg), CsA and PRVT (5 mg/kg), or a combination of CsA, LSRT,
      and PRVT for 28 days. Basic parameters (renal function, systolic blood pressure,
      serum high-sensitivity C-reactive protein [hs-CRP], and lipid profiles),
      histopathology (arteriolopathy, tubulointerstitial fibrosis, and inflammatory
      cell infiltration), and inflammatory and fibrotic factors (intrarenal CRP,
      angiotensin II, osteopontin, and transforming growth factor [TGF]-beta1) were
      studied. RESULTS: LSRT or PRVT treatment significantly attenuated the
      histopathologic changes induced by CsA, and combined treatment with LSRT and PRVT
      further decreased these parameters compared with giving each drug alone.
      Increased levels of angiotensin II, intrarenal CRP, osteopontin, and TGF-beta1 in
      CsA-treated rat kidney were reduced by treatment with either LSRT or PRVT and
      were further decreased by the combination of the two drugs. There were no
      significant differences in systolic blood pressure or serum lipid parameters
      between groups. CONCLUSIONS: Combined treatment with LSRT and PRVT provided
      synergistic effects in attenuating inflammatory and fibrotic processes in a rat
      model of chronic CsA-induced nephropathy, and this effect was independent of
      their hypolipidemic and hypotensive actions.

PMID- 15940042
TI  - Vascular endothelial growth factor increases functional beta-cell mass by
      improvement of angiogenesis of isolated human and murine pancreatic islets.
AB  - BACKGROUND: Blood flow is impaired in islet transplants, but there is conflicting
      evidence on improving the outcome by promoting vascularization. We previously
      reported that islet endothelial cells (EC) possess significant angiogenic
      capacity. METHODS: To further address this issue, we studied human islets in
      culture under hypoxic conditions. Moreover, we used a transgene mouse model with
      human vascular endothelial growth factor (VEGF) production in beta-cells under
      the control of the rat insulin promoter (RIP) to stimulate islet EC
      proliferation. RESULTS: Subsequent to a hypoxic stimulus, islets responded with
      specific expression patterns of VEGF and fibroblast growth factor; however, this
      was not sufficient to prevent the decay of islet EC. VEGF release of RIP-VEGF
      transgenic islets was controlled by glucose and resulted in the formation of
      sprouts. When transplanted to the kidney capsule of diabetic mice, RIP-VEGF
      islets significantly enhanced microvascular density and functional blood flow to
      the graft compared with controls. CONCLUSIONS: Optimized angiogenesis of islet
      transplants resulted in greater availability of insulin caused by beta-cell
      proliferation and a significantly higher percentage (90% versus 20%) of mice
      cured from diabetes.

PMID- 15940043
TI  - Immunosuppression with a combination of pg490-88 and a subtherapeutic dose of
      FK506 in a canine renal allograft model.
AB  - BACKGROUND: PG490-88 is a water soluble, semisynthetic derivative of a novel
      compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii
      Hook F. In this study, we evaluated the immunosuppressive effect of PG490-88
      alone or combined with FK506 in a dog renal transplantation model. METHODS:
      Recipient and donor male beagle dogs were obtained from different breeders to
      ensure MHC mismatching. PG490-88 and/or FK506 were administered orally based on
      protocol design. RESULTS: All dogs in the untreated group developed acute
      vascular rejection with a median survival time of 6 days. The grafts from this
      group presented with massive hemorrhage, IgM, IgG, and C4c deposition.
      Administration of PG490-88 0.06 mg/kg/day significantly prolonged graft survival
      to a median survival time of 11 days (P=0.038, vs. control). Treatment with FK506
      0.3 mg/kg/day did not prolong graft survival with a median survival time of 9
      days. Although FK506 0.6 mg/kg/day significantly prolonged survival, this dose
      was not tolerated by the dogs. The combination of PG 0.06 mg/kg/day and FK506 0.3
      mg/kg/day significantly prolonged survival to a median survival time of 15 days
      (P=0.017, vs. control). Compared to the untreated control group, the pattern of
      acute humoral rejection was attenuated in renal allografts treated with PG490-88
      and/or FK506. C4c deposition was significantly decreased in renal allografts
      treated with PG490-88 monotherapy and combination therapy. CONCLUSIONS: PG490-88
      alone and combined with low dose FK506 significantly prolonged renal allograft
      survival in a dog model. This agent attenuated acute humoral rejection by
      inhibiting complement activation and T-cell infiltration.

PMID- 15940044
TI  - Transplantation of discordant xenogeneic islets using repeated therapy with anti
      CD154.
AB  - BACKGROUND: Costimulatory blockade has been shown to allow long-term survival of
      xenogeneic islets. The aim of the present study was to analyze the possibility of
      xenogeneic islet retransplantation using costimulatory blockade. METHODS:
      Streptozotocin-induced diabetic C57/BL6 mice were transplanted with 1000 human
      islet equivalents. After 14 days, mice were nephrectomized (graftectomy) and
      retransplanted with human leukocyte antigen (HLA)-mismatched human islets under
      contralateral kidney capsule. Four groups were performed: I: all transplants (Tx)
      without MR1; II: first Tx without MR1, second Tx with MR1; III: first Tx with
      MR1, second Tx without MR1; and IV: all Tx with MR1. Recipient serums were
      analyzed by cross-match for serum-mediated cytotoxicity against human lymphocytes
      and islets. RESULTS: In group I, the second graft rejection was accelerated
      (graft survival, 5 +/- 3 days) compared with the first graft without MR1 (13 +/-
      7 days). In groups II and III, second graft survivals were 16 +/-1 3 and 62 +/-
      15 days, respectively. In group IV, second graft function was maintained for >100
      days. Pretransplant cross-matches were all negative. Post-second Tx cross-matches
      were positive in groups I and II and negative in group IV. In group III, post
      second Tx cross-matches were negative only for cells with HLA molecules present
      in the first donor. CONCLUSIONS: MR1 was unable to induce tolerance after
      sensitization. MR1 given at the first Tx only allowed prolonged survival of the
      second Tx, but rejection still occurred with development of antibodies against
      molecules not present on first donor cells, indicating that costimulatory
      blockade does not induce linked-suppression against species-specific antigens of
      xenografts but can induce donor-specific unresponsiveness. MR1 given for all
      sequential transplantation allowed long-term regraft survival and prevented
      occurrence of antidonor antibodies.

PMID- 15940045
TI  - FTY720, a novel immunomodulator: efficacy and safety results from the first phase
      2A study in de novo renal transplantation.
AB  - BACKGROUND: FTY720 is the first of a new drug class: sphingosine-1-phosphate
      receptor agonist. Its effect relates to the modulation of lymphocytes trafficking
      from blood and peripheral tissues to lymph nodes. This is the first study to
      evaluate the efficacy and safety of FTY720 in de novo renal transplantation.
      METHODS: This phase 2a, multicenter, open-label, dose-finding study compared
      FTY720 (0.25, 0.5, 1.0, or 2.5 mg) with mycophenolate mofetil (MMF), in
      combination with cyclosporine and corticosteroids. Patients (n=208) received
      FTY720 (n=167) or MMF (n=41) for 3 months followed by a 3-month follow-up.
      RESULTS: The incidence of biopsy-confirmed acute rejection at month 3 was 23.3%,
      34.9%, 17.5%, and 9.8%, respectively, with FTY720 at doses of 0.25, 0.5, 1.0, and
      2.5 mg, versus 17.1% with MMF. The incidence for the composite endpoint (biopsy
      confirmed acute rejection, graft loss, or death) was lowest with FTY720 at a dose
      of 2.5 mg at month 3 (14.6%) compared with FTY720 at doses of 0.25 mg (25.6%),
      0.5 mg (34.9%), and 1.0 mg (17.5%), and MMF (19.5%). Safety was comparable
      between FTY720 and MMF group. The main difference in tolerability was a mild and
      transient reduction in heart rate. A decrease in peripheral lymphocytes occurred
      in patients receiving FTY720, as expected from the mode of action, and this was
      reversible after treatment cessation. CONCLUSIONS: FTY720 at 2.5 mg was found to
      be as effective as MMF in combination with cyclosporine for the prevention of
      acute rejection after renal transplantation. FTY720 was well tolerated and not
      associated with the side effects commonly observed with immunosuppressant
      therapies.

PMID- 15940046
TI  - Physiologic impact of low-dose dopamine on renal function in the early post renal
      transplant period.
AB  - BACKGROUND: Low-dose dopamine (LDD) (< or =5.0 microg/kg/min) is often used in
      the early postrenal transplant period for its perceived improvements in renal
      function parameters. However, there is little published evidence to support its
      use. The aim of this study was to evaluate the effects of LDD on the physiologic
      parameters of the transplanted kidney. METHODS: With local ethics approval, 20
      consecutive adult patients (age range, 27-74 years), who underwent cadaveric
      renal transplantation with cyclosporine immunosuppression, were randomized into
      two study groups, each with 10 patients. The study period was over 9 hrs on the
      first postoperative day. This 9-hr block was divided into three 3-hr periods.
      Patient group 1 received a dopamine infusion over the second 3-hr period only,
      and patient group 2 received a dopamine infusion over both the first and third 3
      hr periods. During these periods, urine flow rate (UFR), effective renal plasma
      flow (ERPF), creatinine clearance (CC), and total urinary sodium excretion rate
      (tUNa) were measured. RESULTS: In both groups, there were significant (P<0.05,
      Wilcoxon rank sum test) increases in ERPF, UFR, CC, and tUNa during LDD infusion
      periods compared with periods of no LDD infusion. No changes in heart rate or
      mean arterial blood pressure were seen with LDD administration. CONCLUSIONS: LDD
      significantly increases ERPF, UFR, CC, and tUNa in the transplanted allograft
      kidney treated with cyclosporine immunosuppression in the early posttransplant
      period.

PMID- 15940047
TI  - The favorable outcome of human islet transplantation in Korea: experiences of 10
      autologous transplantations.
AB  - BACKGROUND: Cystic neoplasms of the pancreas are an increasingly diagnosed
      entity, and surgical resection of the pancreas is advocated. Islet
      autotransplantation is a therapeutic approach used to prevent diabetes in cases
      of pathologically benign neoplasm after major pancreatectomy. METHODS: A total of
      10 patients underwent pancreatectomy with islet autotransplantation. To evaluate
      islet transplantation efficiency, the authors compared 23 subjects who did not
      undergo islet transplantation after partial pancreatectomy with 87 subjects with
      normal glucose tolerance and with 77 diabetic subjects that did not undergo
      pancreatectomy. RESULTS: Ten female patients with nine cystic neoplasms and one
      patient with pancreatic injury underwent transplantation. Their mean islet
      equivalents (IEQ) was 3,159 IEQ/kg. During follow-up, two recipients required
      insulin or oral agents. At the 12-month follow-up, homeostasis model assessment
      (HOMA)-beta was 77.36+/-17.68, the insulinogenic index (INSindex) was 0.49+/
      0.11, and fasting C-peptide and hemoglobin A1c were 1.28+/-0.18 ng/mL and 5.73+/
      0.26%, respectively. Islet replacement was found to increase HOMA-beta by
      approximately 17% compared with distal pancreatectomy in normal glucose tolerance
      subjects without islet autotransplantation and by 46% compared with distal
      pancreatectomy diabetes subjects without islet autotransplantation. Factors
      different in the two insulin and oral hypoglycemic agent (OHA)-requiring
      recipients and the eight insulin- and OHA-free recipients were pancreatectomy
      extent, preoperative glucose metabolism insufficiency, age, and underlying cystic
      neoplasm disease. CONCLUSIONS: Even partial islet graft function can have a
      beneficial metabolic effect on the recipient in terms of metabolic parameters
      such as HOMA-beta and INSindex. This study suggests that islet replacement should
      be considered for experimental procedures in benign pancreatic conditions.

PMID- 15940048
TI  - Mycophenolate mofetil for renal dysfunction after pediatric liver
      transplantation.
AB  - BACKGROUND: Cyclosporine A (CsA) and tacrolimus (Tac) provide effective
      immunosuppression after orthotopic liver transplantation (OLT) but can cause
      renal dysfunction that may progress to end-stage renal failure (ESRF).
      Mycophenolate mofetil (MMF) is a newer immunosuppressant that does not affect
      renal function. Its long-term use in children with renal dysfunction after OLT
      has not yet been fully evaluated. METHODS: A retrospective analysis was performed
      of all children begun on MMF for renal dysfunction and followed up for at least 1
      year. Renal dysfunction was defined as calculated glomerular filtration rate
      (cGFR) of less than 65 mL/min/1.73 m2. cGFR and liver function were measured
      before and after transfer. Data were analyzed using the Wilcoxon signed rank
      test. RESULTS: Forty-eight children (23 males) began MMF at a median age of 11.1
      (0.9-18.1) years and at a median of 4.0 (0.3-12.4) years postOLT. Median baseline
      cGFR was 54 (range 29-65) mL/min/1.73 m2. Immunosuppression after transfer was
      MMF monotherapy in 36, MMF with steroids, in 4 and MMF with low-dose CsA or Tac
      in 8. In 44 (92%) patients, there was a statistically significant increase to a
      median cGFR of 69 (28-114) mL/min/1.73 m2 by 1 month and a further increase to a
      median cGFR of 77 (24-105) mL/min/1.73 m2 by 2 months of MMF treatment, after
      which time cGFR was maintained. Children aged less than 3 years at OLT or who
      were less than 5 years postOLT when MMF was begun demonstrated greater increases
      in cGFR. Four children with a median baseline cGFR of 34 (range 31-49)
      mL/min/1.73 m2 did not respond and progressed to ESRF. Mild side effects occurred
      in seven (15%) and gastrointestinal bleeding requiring discontinuation of MMF in
      one (2%). Liver function abnormalities occurred in seven (15%): transient
      transaminitis in three, acute rejection in two, and chronic rejection in two, of
      whom one required retransplantation. CONCLUSIONS: In 92% children with renal
      dysfunction after OLT, MMF treatment provided safe and effective
      immunosuppression and allowed CsA or Tac to be discontinued or reduced, leading
      to improvement of renal function. The improvement was greatest in younger
      children and those who began MMF early postOLT. Side effects were uncommon.
      Additional steroid cover during the transfer to MMF should be considered to
      prevent liver-allograft rejection.

PMID- 15940049
TI  - Anti-human leukocyte antigen antibodies are associated with restenosis after
      percutaneous coronary intervention for cardiac allograft vasculopathy.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) to palliate cardiac
      allograft vasculopathy (CAV) has been associated with high restenosis rates,
      possibly related to increased inflammation associated with this disease. Whether
      markers of immunologic rejection are associated with restenosis in this
      population is unknown. The goal of the study was to determine the predictors of
      restenosis after PCI for CAV. METHODS: Records were reviewed retrospectively from
      a single, high-volume cardiac transplant center. Clinical, angiographic, and
      immunologic data were collected on all patients postorthotopic heart
      transplantation (OHT) that had subsequent PCI. Restenosis was defined as greater
      than 50% stenosis at the previous intervention site. RESULTS: PCI was
      successfully performed on 62 de novo lesions in 40 patients an average of 6.8+/
      3.9 years after OHT. Angiographic follow-up data was available for 79%, with an
      average follow-up of 1.54+/-1.22 years. The 1-year restenosis rate was 49% (64%
      for balloon percutaneous transluminal coronary angioplasty and 33% for coronary
      stenting [P=0.09 for difference]). The frequency of immunoglobulin (Ig)G antibody
      to major histocompatibility complex (MHC) class I antigen was highly associated
      with risk of restenosis (hazard ratio [HR] 11.33, P=0.01). Greater stenosis
      severity and smaller target vessel diameter were also predictors of restenosis as
      in the nontransplant population. CONCLUSIONS: The findings suggest that in
      patients postPCI for CAV, humoral allo-immunity may contribute to restenosis and
      that IgG antibodies to MHC class I antigen may help predict the risk of
      restenosis after PCI in this population.

PMID- 15940050
TI  - Prevalence and correlates of self-reported pretransplant nonadherence with
      medication in heart, liver, and lung transplant candidates.
AB  - BACKGROUND: Evidence on prevalence and correlates of pretransplant medication
      nonadherence (MNA) is limited. The present study explored self-reported
      prevalence and correlates of MNA before heart, liver, and lung transplantation.
      METHODS: This cross-sectional descriptive study included 174 patients: 69 lung,
      33 heart, and 72 liver transplant candidates. MNA was assessed by self-report
      using the following question: "During the past 14 days, how often did you not
      take your medication?" Patients scoring once or higher on a five-point rating
      scale were considered to be nonadherent. Correlates of MNA explored were
      demographics, anxiety and depression (Hospital Anxiety and Depression Inventory),
      personality traits (NEO Personality Inventory-Revised), perceived health status
      (Euro-QOL), and social support (Social Support Questionnaire). RESULTS:
      Prevalence of pretransplant MNA was 16.7% and was comparable among the three
      groups. After correction for multiple comparisons (i.e., P=0.01), higher
      educational level (P=0.006) was related to MNA. Less severe depression (P=0.069),
      lower scores on the personality trait conscientiousness (P=0.021), and less
      received social support (P=0.062) tended to be related to MNA. Multiple logistic
      regression revealed that higher educational level (P=0.008), lower received
      social support (P=0.013), and lower conscientiousness (P=0.023) were independent
      predictors of pretransplant MNA. CONCLUSIONS: Several correlates of MNA allow
      identification of patients at risk for pretransplant MNA.

PMID- 15940051
TI  - Successful low toxicity hematopoietic stem cell transplantation for high-risk
      adult chronic granulomatous disease patients.
AB  - BACKGROUND: Allogeneic hematopoietic stem cell transplantation for chronic
      granulomatous disease (CGD) is associated with a significant risk of transplant
      related mortality. Adult age, overt infection, and residual inflammatory disease
      at transplant are major risk factors. METHODS: Here we report the favorable
      outcome after bone marrow transplantation in three high-risk adult CGD patients
      (ages 18, 35, and 39) with severe disease-related complications (overt pneumonia,
      liver abscess, steroid-dependent granulomatous colitis, diabetes, restrictive
      lung disease, renal insufficiency, epilepsia). Bone marrow donors were human
      leukocyte antigen-matched related or unrelated. The conditioning regimen
      consisted of 2 x 4 mg/kg oral busulphan (d -3, -2), fludarabine 6 x 30 mg/qm (d 
      7 to -2), rabbit anti-T-cell-globulin (Fresenius) 4 x 10 mg/kg (d -4 to -1).
      Graft versus host disease prophylaxis consisted of cyclosporine A and
      mycophenolate-mofetil. RESULTS: Mean neutrophil and platelet engraftment was
      observed at day +18.5 and +22.5, respectively. All infectious and inflammatory
      lesions resolved and restrictive lung disease improved. No signs of grade II-IV
      acute or chronic graft versus host disease were observed. With a follow-up of 12
      to 27 months, all patients are alive and well with full donor chimerism,
      normalized superoxide production, and documented T- and B-cell function.
      CONCLUSION: This modified reduced intensity conditioning protocol is a promising
      treatment modality for high-risk adult CGD patients.

PMID- 15940052
TI  - Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in
      a patient with severe osteogenesis imperfecta.
AB  - BACKGROUND: Mesenchymal stem cells (MSC) are progenitors of mesenchymal tissues
      such as bone, cartilage, and adipose. Adult human leukocyte antigen (HLA)-matched
      MSC have been used in cellular therapies of bone disorders such as osteogenesis
      imperfecta, with promising results. METHODS: A female fetus with multiple
      intrauterine fractures, diagnosed as severe osteogenesis imperfecta, underwent
      transplantation with allogeneic HLA-mismatched male fetal MSC in the 32nd week of
      gestation. Engraftment analyses of donor cells, immunologic reaction against
      donor cells, and the well-being of the patient were assessed. RESULTS: At 9
      months of age, on slides stained for osteocalcin or osteopontin, a centromeric XY
      specific probe revealed 0.3% of XY-positive cells in a bone biopsy specimen.
      Whole Y genome fluorescent in situ hybridization staining showed a median of 7.4%
      Y-positive cells (range, 6.8%-16.6%). Bone histology showed regularly arranged
      and configurated bone trabeculae. Patient lymphocyte proliferation against donor
      MSC was not observed in co-culture experiments performed in vitro after MSC
      injection. Complementary bisphosphonate treatment was begun at 4 months. During
      the first 2 years of life, three fractures were noted. At 2 years of corrected
      age, psychomotor development was normal and growth followed the same channel, -5
      SD. CONCLUSIONS: The authors' findings show that allogeneic fetal MSC can engraft
      and differentiate into bone in a human fetus even when the recipient is
      immunocompetent and HLA-incompatible.

PMID- 15940053
TI  - IL-10 promoter gene polymorphism associated with the occurrence of chronic GVHD
      and its clinical course during systemic immunosuppressive treatment for chronic
      GVHD after allogeneic peripheral blood stem cell transplantation.
AB  - BACKGROUND: The current study attempted to evaluate the association between IL-10
      promoter gene polymorphism and transplant outcomes including the occurrence of
      chronic graft-versus-host disease (GVHD) and its clinical course during systemic
      immunosuppressive treatment (IST) among 60 recipients of cytokine-mobilized
      peripheral blood stem cell (PBSC) from HLA-matched sibling donors. METHODS: We
      analyzed 3 single-nucleotide polymorphisms in proximal region of IL-10 promoter
      gene (-1082/-819/-592). RESULTS: In the current study, only two haplotypes
      (1082*A/819*T/592*A [ATA] and 1082*A/819*C/592*C [ACC]) were found. An increased
      occurrence of chronic GVHD was noted dependent on the IL-10 haplotypes (43% vs.
      68% vs. 96% in ACC/ACC vs. ATA/ACC vs. ATA/ATA haplotype, P=0.003). In a logistic
      regression based on multinomial model, ATA/ATA homozygote had 7-fold increasing
      risk of the development of chronic GVHD compared with ACC/ACC homozygote. The
      incidence of chronic GVHD at 1 year was 46%+/-20%, 64%+/-10%, and 82%+/-5% in
      ACC/ACC, ATA/ACC and ATA/ATA group, respectively (P=0.0266). Plus, the duration
      of systemic IST was significantly shorter in recipients without ATA-haplotype
      comparing with those with ATA haplotype (339 days vs. 1,146 days, P=0.0091).
      CONCLUSION: IL-10 promoter gene polymorphism was found to be apparently
      associated with chronic GVHD after allogeneic peripheral blood stem cell
      transplantation from HLA-matched sibling donors.

PMID- 15940054
TI  - Costimulation blockade followed by a 12-week period of cyclosporine A facilitates
      prolonged drug-free survival of rhesus monkey kidney allografts.
AB  - Costimulation blockade as a single immunosuppressive treatment modality is not
      sufficient to prevent graft rejection. Here, we report an induction therapy using
      antagonistic antibodies against CD40 and CD86, given twice weekly from day -1
      until day 56, followed by a delayed 12-week course of low-dose cyclosporine A
      (CsA) treatment in the rhesus monkey kidney-allograft model. Low-dose CsA
      treatment was initiated on day 42 and tapered until total cessation of all
      treatment on day 126. Treatment with anti-CD40/86 alone resulted in graft
      survival of 61, 71, 75, 78, and 116 days. Costimulation blockade followed by CsA
      resulted in more than 3-year drug-free survival in two of four animals. None of
      the animals developed donor-specific alloantibodies. Transforming growth factor
      beta producing cells are present in early as well as in late kidney-graft
      biopsies and could play a role in the observed long-term drug-free graft
      survival.

PMID- 15940055
TI  - Novel in vivo murine model to study islet potency: engraftment and function.
AB  - Standard islet potency testing uses transplantation of islets under the kidney
      capsule in diabetic severe combined immunodeficient (d-SCID) mice. Even though it
      is possible to achieve normoglycemia in the majority of recipients by this
      method, the surgical procedure, by itself, is technically difficult and
      associated with an appreciable mortality of animals. In addition, the spatially
      limited renal subcapsular site restricts the mass of islet tissue that can be
      transplanted. Matrigel basement membrane matrix (MATRIGEL), extracted from a
      mouse sarcoma, is rich in angiogenic growth factors and has been shown to support
      the growth of mammalian cells using murine models. In this report we demonstrate
      that subcutaneous islet transplantation with MATRIGEL can effectively achieve
      normoglycemia and that this is a simple and reproducible model for in vivo islet
      potency testing in d-SCID mice that overcomes many drawbacks of the conventional
      method of kidney subcapsular islet transplantation.

PMID- 15940056
TI  - Solid-organ transplantation in HBsAg-negative patients with antibodies to HBV
      core antigen: low risk of HBV reactivation.
AB  - Hepatitis B virus (HBV) reactivation is a well-described event in HBV surface
      antigen (HbsAg)-positive patients undergoing immunosuppression. There are only
      few data about the risk of HBV reactivation in HBsAg-negative solid-organ
      transplant recipients with resolved HBV infection. We conducted a systematic
      screening of serum and liver samples from 38 HBsAg-negative and anti-HBV core
      antigen (anti-HBc)-positive patients for the presence of HBV-DNA and for
      serologic HBV markers before and after solid-organ transplantation (kidney, n=23;
      liver, n=9; heart, n=6). Pretransplant prevalence of HBV-DNA was 24% (6/25) in
      serum and 33% (3/9) in liver samples. Forty-four percent (15/34) of the
      recipients were viremic after transplantation; this finding was more common in
      patients coinfected with hepatitis C (P=0.011) and in patients negative for anti
      HBs (P=0.001). Two recipients became antigenemic (HBsAg-positive), but none
      developed clinical signs of hepatitis. In conclusion, subclinical reactivation of
      HBV infection was detected in a significant proportion of HBsAg-negative solid
      organ-transplant recipients.

PMID- 15940057
TI  - Partial splenic embolization for the treatment of hypersplenism in liver
      transplanted patients with hepatitis C virus recurrence before peg-interferon
      plus ribavirin.

PMID- 15940058
TI  - Hepatic mucormycosis in a renal transplant recipient.

PMID- 15940059
TI  - Expanded efficacy and indication of extracorporeal membrane oxygenation for
      preoperative pulmonary bleeding on pediatric cadaveric orthotopic liver
      transplantation.

PMID- 15940060
TI  - Digital cine angiography permits radiation dose reduction without reduction in
      image quality.
AB  - PURPOSE: To investigate how much the radiation dose in digital cine angiography
      (DCA) systems can be reduced while maintaining an image quality equivalent to
      that of conventional cine angiography (CCA). MATERIALS AND METHODS: Simulated
      vessel phantoms were subjected to DCA and CCA. In DCA, the input dose value to
      the image intensifier built in the system was 0.10, 0.12, 0.14, 0.17, 0.2, and
      0.24 microGy. The detectability for simulated vessel phantoms was visually
      evaluated by five observers. The radiation dose was measured using
      radiofluorescent glass-rod dosimeters. Doses of digital cine imaging were
      measured as relative values with the dose of CCA considered as 1.0. RESULTS: The
      relative DCA/CCA values in DCA, measured by radiofluorescent glass-rod
      dosimeters, ranged from 0.414 to 0.901 for simulated vessel phantoms CONCLUSION:
      DCA allows a reduction by 59% of the radiation dose compared with CCA without
      reduction of image quality.

PMID- 15940061
TI  - Stage I and II non-Hodgkin's lymphoma: results of combined of THP-COP
      chemotherapy and radiotherapy.
AB  - PURPOSE: We evaluated the usefulness of radiotherapy plus THP-COP chemotherapy
      consisting of cyclophosphamide, vincristine, pirarubicin (tetrahydropyranyl
      adriamycin, THP), and prednisone for stage I and II non-Hodgkin's lymphoma (NHL).
      PATIENTS AND METHODS: Between October 1998 and October 2001, 32 patients with
      Stage I or II NHL were treated with THP-COP plus radiotherapy. The patients
      consisted of 19 men and 13 women with a median age of 60 years (range, 23-81
      years). The histological type was intermediate grade in 29, high in one, and
      unclassified in two. The number of cycles of THP-COP ranged from three to six
      (median, three cycles). Doses of irradiation ranged from 18.0 to 46.5 Gy (median,
      40.0 Gy). The median length of follow-up was 19 months (range, 1-47 months).
      RESULTS: The 3-year overall survival rate and progression-free survival rate were
      81.3% and 74.9%, respectively. Leukopenia of grade 3-4 was documented in 24
      patients (75%) and thrombopenia of grade 3-4 in four (12.5%). CONCLUSION: THP-COP
      plus radiotherapy appeared to be feasible for stage I and II NHL patients.
      However, further evaluation is needed to determine the usefulness of this
      treatment.

PMID- 15940062
TI  - A method for reducing radiation dose in cerebral CT perfusion study with variable
      scan schedule.
AB  - PURPOSE: To propose a method for reducing the radiation dose in cerebral CT
      perfusion studies by using a variable scan schedule. MATERIALS AND METHODS:
      Original images were obtained with a multi detector-row CT (MDCT) scanner using
      the following CT perfusion protocol: continuous scans of 1 sec/rotation x 60 sec,
      four 5-mm-thick contiguous slices. The original images were thinned-out using
      combinations of various numbers of former continuous images (10, 15, 20, 25, and
      30), and the later skipped images with various scan intervals (2, 5, 10, 15 and
      20 sec). The thinned-out images were interpolated by linear interpolation. In
      five patients with cerebrovascular disease, we generated functional images of
      cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time
      (MTT) from both original and interpolated data. The correlation coefficients (CC)
      for these parameters between the original and interpolated images were evaluated.
      RESULTS: The CC decreased with dose reduction. To keep the correlation
      coefficients greater than 0.9, the estimated dose was reduced to 33.3% on CBF
      with a set of 10 continuous images and scan interval of 5 sec, to 20.0% on CBV
      with a set of 10 continuous images and scan interval of 20 sec, and to 58.3% on
      MTT with a set of 10 continuous images and scan interval of 2 sec. CONCLUSION:
      The variable scan schedule method would be useful to reduce radiation dose while
      maintaining the accuracy of CT perfusion (CTP) parameters.

PMID- 15940063
TI  - Full-size digital storage phosphor chest radiography: effect of 4K versus 2K
      matrix size on observer performance in detection of subtle interstitial
      abnormalities.
AB  - PURPOSE: To compare observer performance in the detection of subtle interstitial
      abnormalities on 3,520 x 3,520 (4K) matrix and 1,760 x 1,760 (2K) matrix full
      size digital storage phosphor (DSP) chest radiographs. MATERIALS AND METHODS:
      Thirty-five 4K DSP chest radiographs with subtle interstitial abnormalities
      (n=27) or normal lungs (n=8) were processed with a half-band low-pass filter to
      produce 2K DSP radiographs. Although the actual matrix size of the 2K DSP
      radiographs remained 4K, the effective matrix size was reduced to 2K. Four chest
      radiologists independently evaluated full-sized hard-copy of the 4K and 2K DSP
      radiographs, and scored the presence of interstitial abnormalities for both right
      and left lungs on a five-point confidence scale. With findings on high-resolution
      computed tomography as the reference standard, observer performance was evaluated
      using multireader-multicase receiver operating characteristic (ROC) analysis.
      RESULTS: The average area under the ROC curve (Az) values for 4K and 2K DSP
      radiographs were 0.791+/-0.055 and 0.804+/-0.050, respectively. Both individual
      and averaged Az values showed no statistically significant differences (p>0.05)
      between 4K and 2K DSP radiographs. CONCLUSION: Observer performance in the
      detection of subtle interstitial abnormalities on 4K full-size DSP chest
      radiographs was equivalent to that on 2K full-size DSP chest radiographs.

PMID- 15940064
TI  - Quantitative evaluation of measurement accuracy for three-dimensional angiography
      system using various phantoms.
AB  - PURPOSE: The purpose of this study was to evaluate the spatial resolution and
      accuracy of three-dimensional (3D) distance measurements performed with 3D
      angiography using various phantoms. MATERIALS AND METHODS: With a 3D angiography
      system, digital images with a 512 x 512 matrix were obtained with the C-arm
      sweep, which rotates at a speed of 30 degrees/second. A 3D comb phantom was
      designed to assess spatial resolution and artifacts at 3D angiography and
      consisted of six combs with different pitches: 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm,
      0.9 mm, and 1.0 mm. Frame rate, field of view (FOV) size, reconstruction matrix,
      and direction of the phantom were changed. In order to investigate the accuracy
      of 3D distance measurements, aneurysm phantoms and stenosis phantoms were used.
      Aneurysm phantoms simulated intracranial saccular aneurysms and parent arteries;
      2-mm- or 4-mm-inner-diameter cylinder and five different spheres (diameter: 10,
      7, 5, 3, 2 mm) were used. Stenosis phantoms were designed to simulate
      intracranial steno-occlusive diseases; the nonpulsatile phantoms were made of
      four cylinders (diameter: 3.0, 3.6, 4.0, 5.0 mm) that had areas of 50% and 75%
      stenosis. The dimensions of the spheres and cylinders were measured on magnified
      multiplanar reconstruction (MPR) images. RESULTS: The pitch of the 0.5 mm comb
      phantom was identified clearly on 3D images reconstructed with a frame rate of 30
      frame/sec and 512(3) reconstruction mode. In any reconstruction matrixes and any
      angles of the phantom, the resolution and artifacts worsened when frame rates
      were decreased. With regard to the angle of the phantom to the axis of rotational
      angiography, spatial resolution and artifacts worsened with increase in angle.
      Spatial resolution and artifacts were better with a FOV of 7 x 7 inch than with
      one of 9 x 9 inch. All spheres on the aneurysm phantom were clearly demonstrated
      at any angle; measurement error of sphere size was 0.3 mm or less for 512(3)
      reconstruction. In 512(3) reconstruction, the error of percent stenosis was 3% or
      less except for a cylinder diameter of 3.0 mm and 5% for a cylinder diameter of
      3.0 mm. CONCLUSION: Spatial resolution of the reconstructed 3D images in this
      system was 0.5 mm or less. Measurement error of sphere size was 0.3 mm or less
      when 512(3) reconstruction was used. When using proper imaging parameters and
      postprocessing methods, measurements of aneurysm size and percent stenosis on the
      reconstructed 3D angiograms were substantially reliable.

PMID- 15940065
TI  - Pathologic significance of low-attenuation hepatic parenchymal abnormalities in
      CT scans of living related donor partial liver transplant recipients.
AB  - PURPOSE: To evaluate the pathologic significance of the low-attenuation changes
      of liver grafts in living donor partial liver transplantation (LDLT) on computed
      tomography (CT). MATERIALS AND METHODS: We retrospectively correlated the low
      attenuation changes of liver grafts which were defined as readings below 50 HU on
      unenhanced CT with histological findings obtained by needle biopsy or surgery
      within seven days of CT studies. The study group included 35 CT findings of 35
      recipients. We classified the low-attenuation change of the liver grafts into a
      homogeneous low-attenuation group and a heterogeneous low-attenuation group.
      RESULTS: Major histologic findings of 35 specimens included cholangitis in 10
      (28.6%), cholestasis in eight (22.9%), fatty change in 15 (42.9%), acute cellular
      rejection (ACR) in 12 (34.3%), acute hepatitis in three (8.6%), liver cell
      ballooning in four (11.4%), massive hepatic necrosis in four (11.4%), and
      centrilobular congestion in five (14.3%) cases, respectively. Homogeneous and
      heterogeneous low-attenuation changes of liver grafts on unenhanced CT were seen
      in 26 (74.3%) and 9 (25.7%) cases, respectively. Massive hepatic necrosis
      occurred more frequently among the heterogeneous low-attenuation group than among
      the homogeneous low-attenuation group. CONCLUSION: Low-attenuation changes in
      liver grafts on CT may indicate a variety of pathological changes. Heterogeneous
      low-attenuation changes suggest massive hepatic necrosis.

PMID- 15940066
TI  - Relationship between hormonal receptors, HER-2, p53 protein, Bcl-2, and MIB-1
      status and the antitumor effects of neoadjuvant anthracycline-based chemotherapy
      in invasive breast cancer patients.
AB  - PURPOSE: The purpose of this study was to evaluate the predictive value of six
      different biological factors for neoadjuvant chemotherapy (NAC) in breast
      conservation treatment (BCT) for invasive breast cancer. MATERIALS AND METHODS:
      Thirty invasive breast cancer patients (31 breasts) who received NAC as BCT and
      needle biopsy before chemotherapy were included in this study. Breast cancer
      tissue was obtained with an 18G core needle with ultrasound guidance. Patients
      received two to five courses of CAF (cyclophosphamide 600 mg/m(2), pirarubicin 20
      40 mg, 5-fluorouracil 600 mg/m(2)). Tissue sections from formalin-fixed paraffin
      embedded blocks were stained for the presence of estrogen receptor (ER),
      progesterone receptor (PgR), HER (human epidermal growth factor receptor)-2, p53
      protein, Bcl-2, and MIB-1 (Ki-67). Tumor reduction rate was assessed by MRI
      before and after chemotherapy. RESULTS: The tumor reduction rate did not differ
      according to the number of courses of chemotherapy administered. In both the
      univariate and multivariate analyses, HER-2-negative status was the only
      significant predictive factor of response (P<0.05). There was no correlation
      between response and hormone receptors, MIB-1, p53 protein, or Bcl-2 expression.
      CONCLUSION: This study suggests that breast cancer cells that overexpress HER-2
      may be resistant to low-doses of anthracycline-based chemotherapy.

PMID- 15940067
TI  - Quantitative evaluation of the pyramidal tract segmented by diffusion tensor
      tractography: feasibility study in patients with amyotrophic lateral sclerosis.
AB  - PURPOSE: Diffusion tensor imaging can evaluate the cerebral white matter
      quantitatively using fractional anisotropy (FA) and also can extract a certain
      tract by tractography, but these two have been used separately and not combined.
      The purpose of this study was to assess the clinical feasibility of ROI analysis
      using diffusion tensor tractography (DTT) in patients with amyotrophic lateral
      sclerosis (ALS). MATERIALS AND METHODS: Sixteen patients with ALS (9 limb-onset
      type, 7 bulbar-onset type) and nine age-matched volunteers were studied. DTT of
      the corticobulbar tract (DTT-CBT) and corticospinal tract (DTT-CST) were
      visualized by free software (dTV/VOLUME-ONE). Regions-of-interest (ROIs) were
      semi-automatically placed on the tracts defined by DTT methods, and FA values
      within the ROIs were measured. RESULTS: Mean FA values of ALS patients in the
      ROIs along the DTT-CST (bulbar-onset: 0.574, limb-onset: 0.594) were
      significantly lower than those of controls (DTT-CST: 0.629) (p<0.05). The mean FA
      of DTT-CBT of the bulbar-onset type (0.509) was significantly lower than that of
      the limb-onset type (0.558) and that of volunteers (0.561). CONCLUSION: DTT could
      segmentate certain white matter tracts and evaluate them quantitatively. It could
      depict the subtle changes between subtypes of ALS as well as the changes between
      the patients and volunteers.

PMID- 15940068
TI  - Intraluminal brachytherapy with metallic stenting in the palliative treatment of
      malignant obstruction of the bile duct.
AB  - PURPOSE: To describe the outcome of intraluminal high-dose-rate (HDR)
      brachytherapy with metallic stenting in patients with obstructing extrahepatic
      cholangiocarcinoma. MATERIALS AND METHODS: Eight patients with inoperable and/or
      unresectable extrahepatic bile duct carcinomas were treated with intraluminal
      brachytherapy (ILBT) followed by self-expandable metallic stent placement.
      Following percutaneous transhepatic drainage, ILBT was delivered by an HDR-Ir-192
      source using the Micro-Selectron afterloading device. Two treatments were planned
      one week apart, with each treatment consisting of a single 10 Gy fraction.
      Biliary patency and palliative effect were assessed by serial labs (including
      bilirubin/alkaline phosphatase), symptomatic improvement, and/or cholangiography.
      RESULTS: All eight patients tolerated the first application of ILBT well, and
      five of them completed two-intraluminal treatments. Six of eight had satisfactory
      control of jaundice until death. Pain relief was observed in four of five (80%)
      and pruritus in six of seven (86%) patients experiencing such symptoms. The mean
      and median times of stent patency were 6.9 and 5 months (range, 4-14),
      respectively. Gastrointestinal bleeding and/or cholangitis occurred in three
      patients. CONCLUSION: HDR ILBT with metallic stenting for patients with
      obstructive jaundice from extrahepatic bile duct carcinoma appears to be feasible
      and associated with acceptable toxicity. These treatments may lead to an improved
      quality of life in these patients.

PMID- 15940069
TI  - Primary synovial sarcoma of the sternum: computed tomography and magnetic
      resonance imaging findings.
AB  - We report the computed tomography (CT) and magnetic resonance imaging (MRI)
      findings of a rare case of synovial sarcoma of the sternum in an 86-year-old man.
      CT demonstrated an inhomogenously enhanced soft-tissue-density mass of the
      sternum that destroyed bone cortex and protruded anteriorly. On MRI, the tumor
      showed a multinodular mass with internal septation and heterogeneous enhancement.
      These CT and MRI findings were nonspecific, but were similar to those of soft
      tissue synovial sarcomas. The tumor was more clearly demarcated by MRI than CT.
      This is the first report concerning the CT and MRI findings of synovial sarcoma
      of the sternum. Synovial sarcoma should be added to the gamut of primary
      malignant neoplasms of the sternum.

PMID- 15940070
TI  - MR imaging of primary malignant lymphoma of the pancreas.
AB  - Pancreatic lymphoma is rare and is usually found as a large pancreatic mass. We
      report the case of a small 2-cm pancreatic lymphoma in a 54-year-old woman that
      had its histological origin in the pancreatic parenchyma. The mass showed
      homogeneously high signal-intensity on T2-weighted images and low signal
      intensity on T1-weighted images. The infiltrative nature and hypovascularity in
      early-phase dynamic contrast study without encasement of arteries and veins were
      well demonstrated by MR imaging and were consistent with malignant lymphoma.

PMID- 15940071
TI  - Simple technique to visualize random set-up displacements using a commercially
      available radiotherapy planning system.
AB  - PURPOSE: To visualize random set-up displacements in isodose distribution images,
      we introduce a simple technique using a commercially available radiotherapy
      planning system (RTP). MATERIALS AND METHODS: A distribution of set-up
      displacement is known to be compatible with that of a Gaussian distribution.
      Based on that assumption, 41 intentionally misaligned beams with 1-mm intervals
      were planned in the respective weights according to Gaussian distribution.
      "Modified" isodose distributions were then visualized using a commercially
      available RTP. In the next step, only two beams misaligned with one standard
      deviation (SD) of the Gaussian distribution were used in place of 41 beams, as a
      large number of beams increases the workload and is unsuitable for clinical use.
      Differences between the two versions of isodose distribution images were assessed
      visually. RESULTS: In modified dose distribution images, the edge of distribution
      was dull compared to normal images. These images show that the larger SD of set
      up displacement dulls the edge of dose distribution. Images from two beams were
      not significantly different to those from 41 beams. CONCLUSION: Using this
      technique, the impact of random set-up displacements was effectively reflected in
      isodose distribution images.

PMID- 15940072
TI  - [Postpartum hemorrhage].
AB  - Postpartum hemorrhage, frequently due to uterine atony, is an important cause of
      maternal death and morbidity. The knowledge of causes, of antenatal and
      intrapartum risk factors and of physiopathological changes in hemodynamics and
      coagulation during pregnancy are essential for the management of the condition.
      At the present time, many efforts are made to organize a multidisciplinary
      approach to this complication of delivery involving clinical and laboratory
      staffs, since the rapid correction of hypovolemia, the diagnosis and treatment of
      defective coagulation, the surgical and pharmacological control of bleeding are
      mandatory. Several medical options have been developed and the surgical
      management includes traditional and newer conservative procedures with variable
      success rates. The developments in the treatment of postpartum hemorrhage may
      reduce hysterectomy that is to be considered the last resort to resolve the
      hemorrhage in some cases. In the modern management of postpartum hemorrhage
      protocols and guidelines should be available in every delivery room.

PMID- 15940073
TI  - [Vulvovaginal candidiasis: a therapeutic approach].
AB  - The vulvovaginal candidiasis represents, after the bacterial vaginosis, the most
      frequent cause of vaginal affection. It is esteemed that around the 75% of the
      women of reproductive age suffered from an episode of vulvovaginitis from candida
      and 40-45% have had more episodes, of which 10-20% in complicated form. The kind
      of candida more frequently isolated in the vagina of symptomatic women is the
      Candida albicans: in the 10-20% of the cases the agent is present in absence of
      symptomatology, and we can almost consider it a saprophytic. On the other hand,
      always with greater frequency fetterses can be isolated of not albicans Candida,
      particularly the tropicalis and the glabrata kind, usually resistant to the
      common therapies. The classification of the vulvovaginal candidiasis proposed by
      Sobel, and by now universally approved, foresees 2 clinical forms of vulvovaginal
      candidiasis, the vulvovaginitis from not complicated candida (VVC) and the
      vulvovaginitis from complicated candida (VVCC): different for pathogenesis,
      elapsed clinical, symptomatology and frequency. They have to be considered in the
      substance 2 different nosological entities, and they request a diagnostic
      approach and a well different therapeutic appointment. In this study we will
      shortly reassume the principal characteristics of it, detaining us on the most
      recent acquisitions in theme of therapy. The base medicines of ac. boric, to
      parity of effectiveness, seem to introduce the most contained cost and the best
      compliance, and they offer him to a complementary use or, in some cases,
      alternative to the more you consolidate therapies with azoli.

PMID- 15940074
TI  - [Treatment of stage IIIB cervical carcinoma. A comparison between radiotherapy,
      concurrent chemo-radiotherapy and neoadjuvant chemotherapy].
AB  - AIM: The aim of this study is to evaluate the effectiveness of radiation,
      concomitant chemoradiation and primary chemotherapy in the treatment of FIGO
      stage IIIB cervical carcinoma. METHODS: Between January 1981 and December 2001 94
      women with stage IIIB FIGO cervical carcinoma were observed. Exclusive
      radiotherapy was administered in 30 cases (32%), radiotherapy and
      radiosensitizing chemotherapy in 20 cases (21%) and primary chemotherapy in 44
      cases (47%); among the latter patients 2 (4%) developed neoplastic progression,
      28 (64%) underwent surgery and 14 (32%) underwent radiotherapy. RESULTS: After a
      median follow-up of 69 months, 5-year overall survival of the 3 groups is
      respectively 23%, 36% and 26% (p=0.7). Total dose to point A greater than 60 Gy
      and the use of brachyradiotherapy are suggestive for a better outcome among women
      treated with radiation therapy (5-year overall survival 31% versus 18%, p=0.8 and
      33% versus 23%, p=0.4, respectively). Radiologically assessed nodal status is the
      only statistically significant risk factor (p=0.001). Although not statistically
      significant, vaginal involvement is a relevant factor influencing survival
      (p=0.1). Women treated with concomitant chemoradiation showed a better 5-year
      disease-free survival (45%) when compared to the other treatment groups
      (radiation alone 27%, primary chemotherapy 30%, p=0.4). CONCLUSIONS: Primary
      chemotherapy, although useful to allow subsequent surgery, does not yield a
      survival advantage with respect to the irradiated patients. Among these,
      concomitant radiosensitizing chemotherapy is likely to improve the disease-free
      survival.

PMID- 15940075
TI  - [Intraepithelial cervical squamous lesions: comparison between PAP-test,
      colposcopy, phase contrast microscopy and histology; usefulness of their synergic
      use].
AB  - AIM: In the last 10 years the tumors of cervix have showed a significant
      reduction in incidence, while the preneoplastic lesions are increased (linked
      often to human papilloma virus [HPV] infection), and so it is enhanced the role
      of early diagnosis. METHODS: The Authors have examined 124 patients at colposcopy
      showing transformation zone anomalies and/or HPV infections. The patients have
      submitted to PAP-test, phase contrast microscopy and to biopsy. RESULTS: The
      analysis of our cases show oneself better sensitivity of colposcopy than
      cytologic exam, in particular in the diagnosis of low grade intraepithelial
      lesions (LSIL), corresponding to CIN 1 and HPV lesions. CONCLUSIONS: Phase
      contrast microscopy, by search of possible preneoplastic elements in the smear,
      is a complementary technique, and if performed systematically and by qualified
      operators allows to reduce furthermore false negative rate. The synergic use of
      tools allows to increase of number of intrecervical neoplasia diagnosis. The
      following cost's increase cannot be considered an obstacle and it is not should
      be necessary to counsel always the colposcopy in case of anomalous PAP smear
      revealed during screening.

PMID- 15940076
TI  - Minilaparotomy vs laparotomy for uterine myomectomies: a randomized controlled
      trial.
AB  - AIM: To evaluate the efficacy and applicability of the minilaparotomy technique
      in abdominal myomectomies and to compare it with traditional laparotomy. METHODS:
      We enrolled 99 women, suffering from symptomatic uterine myomas, to be operated
      for myomectomy. Through computer randomization, 55 women were assigned to the
      study group (minilaparotomy) and 44 women to the control group (traditional
      laparotomy). Women assigned to the study group were operated using a recently
      modified minilaparotomy technique. Statistical evaluation was performed through
      Mann-Whitney U test, chi2 test, Student's t-test. RESULTS: Duration of surgery,
      time for spontaneous recanalization and days of postoperative hospital stay were
      significantly lower in the study group, as well as treatment satisfaction
      reported by the patients (p<0.05). Moreover, each minilaparotomy operation ended
      by saving 620 Euro. CONCLUSIONS: Minilaparotomy seems to be a valid alternative
      to the removal of symptomatic uterine myomas. The objective and subjective
      advantages in operated patients, as well as the reduction in sanitary costs are
      underlined.

PMID- 15940077
TI  - [Preeclampsia and high serum levels of homocysteine].
AB  - AIM: Preeclampsia, a syndrome that can arise in the second half of pregnancy and
      that is characterised essentially by the presence, alone or variously combined,
      of three symptoms, oedemas, proteinuria and hypertension, has an incidence which
      varies between 5-7% and 25%. It seems that the element which determines the start
      and the continuation of the syndrome is located in the placenta and, in
      particular, in structural and functional changes of the trophoblast syncytium. In
      addition, the literature contains numerous studies that have evidenced
      endothelial damage as a key element to the pathogenetic mechanism in EPH-gestosis
      and recently an important role is attributed to a condition of
      hyperhomocysteinaemia. METHODS: Blood samples obtained from 30 primigravidas with
      term pregnancies and physiological course were taken within 1 week of delivery
      and from the same number of primigravidas hospitalised for preeclampsia. RESULTS:
      The homocysteine levels observed were significantly higher in women with
      preeclampsia (8.8+/-2.7 mol/l compared with the control group (4.1+-1.8 mol/l)
      (P<0.05). Haematocrit values measured on the day the sample was taken did not
      present any particular differences in the two groups. CONCLUSIONS: Our research,
      carried out on gravid patients at term of a physiological pregnancy and without
      intercurrent diseases and on primigravidas with preeclampsia who came to our
      observation at the moment of delivery and with a negative history for chronic
      hypertension, diabetes or other, showed a high concentration of homocysteine in
      the primigravidas with preeclampsia close to childbirth.

PMID- 15940078
TI  - Congenital heart disease: a retrospective study of their frequency.
AB  - AIM: An early diagnosis of congenital heart disease (CHD) is necessary for the
      obstetrical management. METHODS: One thousand five hundred and fifty-six pregnant
      women underwent a fetal 2-D echocardiography from 1991 to 2002. We assessed
      patients who had the most common risk factor (RF): family history of CHD,
      diabetes mellitus, teratogen drugs, polyhydramnios, abnormal fetal growth, fetal
      arrhythmia, maternal age over 40 years, maternal autoimmune disease, maternal
      disease contracted during pregnancy, oligohydramnios, only umbilical artery,
      uncorrected visualization in the first level 2-D fetal echocardiography. RESULTS:
      In 110 morphological anomalies found 54 were complex. The malformations are not
      equally distributed among the different RF. The most common RF is the family
      history of CHD where 24 patients showed complex malformations. Another high
      percentage of complex malformations was found in patients with no apparent
      presence of RF: the diagnosis was done after an uncorrected cardiac visualization
      in the first level 2-D echocardiography. In the minor cardiomyopathies we did not
      find the prevalence of any RF. After diagnosis of complex malformations we had
      15% of termination of pregnancies, 37% of the newborns are alive and in good
      health. CONCLUSIONS: The first RF is the family history of CHD, but a correct
      first level fetal 2-D echocardiography is necessary because a very high
      percentage of complex malformations is seen in infant whose mother did not have
      any RF. Ninety percent of cardiac malformations where seen in a 4 chamber view,
      and it is of the utmost importance also for a correct diagnosis of minor
      cardiomyopathies where we did not find a predominant RF.

PMID- 15940079
TI  - The importance of Doppler ultrasonography in the management of fetal growth
      restriction.
AB  - AIM: To evaluate the importance of Doppler ultrasonography in fetuses in the
      management of fetal growth restriction (FGR). METHODS: Sixty-five pregnant women,
      aged between 23 to 39 years and from 27 to 37 weeks of pregnancy were selected;
      they all carried a single fetus showing a diminished growth curve in respect to
      the previous echographic examinations. Women affected with diabetes types I and
      II, renal pathologies and/or past endocrinopathies were excluded. All the
      patients with fetal growth restriction underwent accurate flussimetric mapping of
      some fetal districts such as umbilical artery and ductus venosus. Modalities of
      birth and the neonatal outcome were also considered. RESULTS: The patients
      selected were divided into 4 groups according to the velocimetrical data. The
      neonatal outcome was positive when the end diastolic flow was present in the
      umbilical artery associated with a normal flow in the ductus venosus. In cases
      where the end diastolic flow was absent in the umbilical artery, the management
      and neonatal outcome varied in relation to the morphology of the flow in the
      ductus venosus: the absence or reverse A phase of the mentioned flow is often
      indicative of acute fetal distress and unfavourable prognosis. Reverse end
      diastolic flow in the umbilical artery was always associated with the
      intrauterine death of the fetus. CONCLUSIONS: Our results confirm the validity of
      Doppler ultrasonography in the management and in the choice of timing for birth
      in cases of fetal growth restriction.

PMID- 15940080
TI  - [Comparison between pre- and postnatal echographic screening of malformative
      uropathies].
AB  - AIM: The aim of this study has been to compare the validity of postnatal
      echographic screening in respect of prenatal echography in early diagnosis of
      malformative uropathies (MU). METHODS: In 6578 infants, who have been submitted
      to fetal echography, and to a postnatal screening of MU in our Neonatal Service
      of Echography (University of Messina), we have compared the diagnostic agreement
      of prenatal with postnatal echography. RESULTS: Our comparison demonstrates that,
      in respect of postnatal screening, only 35.71% of pyelectasies and 73.17% of
      hydronephrosis have been diagnosed by fetal echography, and, in particular, only
      18.75% of no-dilated MU. CONCLUSIONS: These data confirm that, in our country,
      the postnatal screening of MU has still significance and suggest that, before
      excluding this screening, it is necessary to verify everywhere the validity of
      fetal echography.

PMID- 15940081
TI  - [''Isolated'' single umbilical artery: incidence, cytogenetic abnormalities,
      malformation and perinatal outcome].
AB  - AIM: The aim of the study was to 1) evaluate the gestational age at diagnosis and
      the incidence of single umbilical artery in an unselected population of 3750
      pregnant women; 2) identify its association with malformations and/or karyotype
      aberrations in pre/postnatal age; 3) evaluate the fetal-neonatal outcome; 4)
      investigate the likelihood that a fetus might be affected by a cytogenetic
      abnormality even in presence of an apparently ''isolated'' single umbilical
      artery. METHODS: Transabdominal ultrasound of the umbilical vessels and
      histological confirmation at birth. In presence of single umbilical artery an
      accurate prenatal ultrasound assessment, karyotyping (pre/postnatal), and
      clinical follow-up after birth were performed. RESULTS: The incidence of single
      umbilical artery in our population resulted 1.07% (40/3750), being ''isolated''
      in 40% of cases. The diagnosis of chromosomal aberration associated with single
      umbilical artery was made in 6 cases (15%), while structural fetal abnormalities
      in absence of causal chromosomal anomalies were present in 9 cases (22.5%), with
      syndromic patterns in 3 of them. In 2 cases with chromosomal anomalies the single
      umbilical artery was apparently ''isolated'' at the ultrasound examination
      between the 17th and the 22nd week of gestation. Excluding 4 terminations of
      pregnancy, the perinatal mortality percentage resulted 25% (9/36); similarly,
      fetal growth retardation was present in 25% of cases (9/36). CONCLUSIONS: The
      incidence of single umbilical artery in our population confirms that this fetal
      vascular anomaly is frequently identified in pregnancy. In the light of our cases
      and data in the literature it is evident that diligent surveillance in prenatal
      age and accurate clinical follow-up after birth are mandatory when a single
      umbilical artery has been diagnosed. Finally, the possibility, even if rare, that
      even when the single umbilical artery is apparently ''isolated'', a chromosomal
      aberration might be present (1/24 of our ''isolated'' cases) should be considered
      when addressing correct counselling to the couples.

PMID- 15940082
TI  - [Water birth and neonatal infections. Experience with 1575 deliveries in water].
AB  - AIM: The aim of our study is to provide an answer on the advantages offered by
      water births, to compare them with 2 other delivery positions and to analyse the
      pathogenous microorganisms present in the water from the bath. METHODS: We
      compared 725 primiparae deliveries in water, 407 primiparae deliveries in bed and
      142 on the delivery stool over the last 7 years. We evaluated the duration of
      labour, perineal trauma, arterial cord blood pH, shoulder dystocia and postpartum
      maternal hemoglobin levels. We have evaluated 200 water samples, taken from the
      bath after filling it and after delivery, and analyzed the pathogenous
      microorganisms and the possibility of neonatal infections. RESULTS: The duration
      (first stage) of labour and the rate of episiotomies was significantly reduced in
      primiparae delivering in water compared with the other delivery positions.
      Nevertheless, the percentage of perineal trauma was not increased. There were no
      differences in the duration of the second stage and arterial umbilical cord blood
      pH. Postpartum maternal hemoglobin levels remained unchanged. No woman delivering
      in the water required analgesics. Infections after water births do not occur more
      frequently than after traditional births. CONCLUSIONS: Our results show that
      water birth has major advantages compared with traditional delivery methods. It
      is associated with a significantly shorter first stage of labour, a lower
      episiotomy rate and reduced analgesic requirements when compared with other
      delivery positions. Provided that the women are selected appropriately, and the
      hygiene rules are respected, water birth is safe for mother and neonate.

PMID- 15940083
TI  - Ectopic pregnancy on previous cesarean section scar. Case report.
AB  - This report concerns a very rare case of ectopic pregnancy on previous cesarean
      section scar, with its clinical therapeutic solutions. The increasing amount of
      cesarean sections could cause, in the next years, a greater probability to meet
      cases such this one. Here it follows a description of the diagnostic iter and the
      surgical therapy with laparotomic approach.

PMID- 15940084
TI  - Combined simple and complex cord knots associated with an encirclement.
AB  - A case of combined simple and a complex knots, and an encirclement of the
      umbilical cord, which did not cause any detectable harm, is presented. The
      combination of a simple and a complex true knots, as described in this paper, is
      a highly unusual phenomenon with only two previous reports in the world
      literature. No report exist showing a combined simple and complex knots and an
      encirclement.

PMID- 15940085
TI  - Voluntary interruption of pregnancy in Europe: medico-legal issues and ethical
      approach to the regulation.
AB  - The legislative criteria of the various European countries, as far as voluntary
      interruption of pregnancy is concerned, differ in the levels of severity employed
      by the law of the single nations. The authors analyze the legislation of some of
      European countries and, as a result, they identify countries that may be defined
      as more tolerant and others where the law is more restrictive. Italy is to be
      dealt with separately, because its legislation as regards this subject presents a
      greater interpretative ambiguity. In the end they analyze religious attitudes
      underlying the laws on voluntary interruption of pregnancy, because of the
      suspicion that the teachings of both Catholic and Protestant theology have
      influenced the differences in the quality of the law in force as regards
      termination of pregnancy is certainly well-grounded, and on the other hand the
      philosophy of law certainly owes its meditation both to theology and to the
      teachings of the Catholic Church.

PMID- 15940086
TI  - Predictors of elevated B-type natriuretic peptide concentrations in dyspneic
      patients without heart failure: an analysis from the breathing not properly
      multinational study.
AB  - STUDY OBJECTIVE: B-type natriuretic peptide (BNP) is an established tool for the
      diagnosis of acute congestive heart failure in patients presenting with dyspnea.
      Some patients have moderately elevated BNP levels (ie, 100 to 500 pg/mL) in the
      absence of acute congestive heart failure. The objective of the current study was
      to identify independent predictors of elevated BNP concentrations in the absence
      of congestive heart failure. METHODS: We studied 781 patients without acute
      congestive heart failure and BNP levels 0 to 500 pg/mL drawn from a cohort of
      1,586 patients with acute dyspnea who had BNP levels measured on emergency
      department arrival. Two cardiologists blinded to BNP results reviewed all
      clinical data and categorized patients according to whether they had acute
      congestive heart failure or not. RESULTS: Independent predictors of elevated BNP
      levels (ie, >100 pg/mL) were a medical history of atrial fibrillation,
      radiographic cardiomegaly, decreased blood hemoglobin concentration, decreased
      body mass index, and increased age. CONCLUSION: Knowledge of these commonly
      obtained variables should aid clinicians in the interpretation of moderately
      elevated BNP results in patients presenting with acute dyspnea in the emergency
      department.

PMID- 15940087
TI  - Changes in the numeric descriptive scale for pain after sublingual nitroglycerin
      do not predict cardiac etiology of chest pain.
AB  - STUDY OBJECTIVE: We determine whether the change in numeric descriptive scale for
      pain after sublingual nitroglycerin use can predict cardiac etiology of chest
      pain. METHODS: A prospective study of a convenience sample of patients who had
      chest pain, presented to the emergency department from May 24, 2001, to April 30,
      2002, and received sublingual nitroglycerin during their evaluation was
      performed. The 11-point numeric descriptive scale for chest pain was recorded
      before and after the initial dose of sublingual nitroglycerin. Cardiac-related
      pain was defined as chest pain in a patient with a discharge diagnosis of
      myocardial infarction or the diagnosis of coronary artery disease based on a
      positive diagnostic study (cardiac catheterization or noninvasive stress
      imaging). Change in the numeric descriptive scale was divided into 4 categories:
      (1) significant/complete reduction; (2) moderate reduction; (3) minimal
      reduction; and (4) no change. RESULTS: The study cohort was composed of 664
      patients: 345 women (52%) and 319 men (48%), mean age 52 years (+/-12.4 years).
      Cardiac-related chest pain was identified in 122 patients (18%). In the overall
      patient population, 125 (19%) patients had no change in pain, 206 (31%) patients
      had minimal reduction, 145 (22%) patients had moderate reduction, and 188 (28%)
      patients had significant or complete reduction in pain. There was no significant
      difference in any subgroup of numeric descriptive scale response to sublingual
      nitroglycerin administration in patients with and without a diagnosis of cardiac
      chest pain. CONCLUSION: In this convenience sample, the response of chest pain to
      sublingual nitroglycerin was not a reliable indicator of a cardiac etiology.

PMID- 15940088
TI  - Images in emergency medicine. Giant pulmonary bulla.

PMID- 15940089
TI  - Point-of-care testing reduces length of stay in emergency department chest pain
      patients.
AB  - STUDY OBJECTIVE: We determine the effect of cardiac troponin I point-of-care
      testing on emergency department (ED) length of stay in chest pain patients.
      METHODS: This was a before-and-after trial in a university-based ED with 75,000
      annual visits. Participants were consecutive patients with a chief complaint of
      chest pain who were admitted to the hospital. During the first 2-week period
      (before), only central laboratory testing of troponin was performed. During the
      second 2-week period (after), treating nurses performed bedside point-of-care
      testing for troponin I, as well as central laboratory testing. Test turnaround
      times, time from triage until calling in admissions, and time from triage until
      patients left the ED to be transferred to a floor (ED length of stay) were
      determined and compared between the 2 study periods. Comparisons between study
      periods are expressed as mean differences with 95% confidence intervals (CIs). A
      sample of 100 patients in each group had 90% power to detect a 1-hour difference
      in length of stay (2-tailed alpha=0.05). RESULTS: There were 232 patients before
      and 134 after introduction of point-of-care testing. Mean age (SD) was 63 years
      (16 years), and 44% were female patients. Baseline characteristics were similar
      in both groups. The rate of positive troponins was also similar (9.5% versus
      6.1%). ED length of stay was significantly reduced after introduction of point-of
      care testing (5.2 hours [95% CI 4.6 to 5.8 hours] versus 7.1 hours [95% CI 6.6 to
      7.7 hours]; mean difference 1.9 hours [95% CI 1.1 to 2.7 hours]). The time until
      the admission was called in to bed control was also significantly reduced by
      introducing point-of-care testing (2.7 hours [95% CI 2.4 to 3.1 hours] versus 4.7
      hours [95% CI 4.3 to 5.0 hours]; mean difference 1.9 hours [95% CI 1.4 to 2.5
      hours]). Point-of-care testing turnaround (14.8 minutes [95% CI 14.1 to 15.5
      minutes]) was significantly shorter than for central laboratory testing (83
      minutes [95% CI 77 to 89 minutes]; mean difference 68 minutes [95% CI 62 minutes
      to 74 minutes]). With central testing as the criterion standard, point-of-care
      testing had a sensitivity of 100% (95% CI 63% to 100%) and a specificity of 96%
      (95% CI 92% to 99%). CONCLUSION: Bedside performance of troponin I point-of-care
      testing by treating nurses significantly reduces ED length of stay.

PMID- 15940090
TI  - Shortness of breath, syncope, and cardiac arrest caused by systemic mastocytosis.
AB  - During a 3-month period, a 33-year-old man presented to the emergency department
      on 4 occasions with dyspnea, palpitations, and syncope. His initial presentation
      was accompanied by acute myocardial injury and ventricular fibrillation. An
      extensive evaluation spanned the 3 months and included echocardiography, cardiac
      catheterization, electrophysiology study, tilt-table evaluation, pulmonary
      angiography, electroencephalography, and serum and urine analysis. Diagnosis
      eluded clinicians until a rash was recognized to be urticaria pigmentosa, and
      biopsy of the rash then implicated mastocytosis. Since the initiation of
      pharmacotherapy nearly 5 years ago, the patient has remained asymptomatic. This
      case demonstrates that systemic mastocytosis can present as recurrent syncope and
      even as cardiac arrest. Diagnosis of this rare but potentially fatal disease is
      made particularly challenging by its protean manifestations.

PMID- 15940091
TI  - Crotalidae polyvalent immune Fab (ovine) antivenom is effective in the
      neutralization of South American viperidae venoms in a murine model.
AB  - STUDY OBJECTIVE: Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) is used
      in the treatment of symptomatic crotaline envenomations in North America. Unlike
      Antivenin (Crotalidae) Polyvalent, which is approved for treatment of crotaline
      envenomation in North and South America, FabAV is manufactured using only venoms
      from crotaline snakes native to the United States. This study was designed to
      evaluate the efficacy of FabAV in the neutralization of venom from 2 South
      American crotaline snakes: Crotalus durissus terrificus (tropical rattlesnake)
      and Bothrops atrox (fer-de-lance). METHODS: A randomized, blinded, placebo
      controlled murine model of intraperitoneal venom injection was used. Venom
      potency was determined in preliminary median lethal dose (LD 50) dosing studies.
      Study animals were then divided into 7 groups: (1) C durissus terrificus venom
      (Sigma-Aldrich Co.)+FabAV, (2) C durissus terrificus venom (Sigma-Aldrich
      Co.)+0.9% normal saline solution, (3) C durissus terrificus venom (Biotoxins
      Inc.)+FabAV, (4) C durissus terrificus venom (Biotoxins Inc.)+normal saline
      solution, (5) B atrox venom+FabAV, (6) B atrox venom+normal saline solution, and
      (7) FabAV+normal saline solution. Twice the estimated LD 50 was the chosen venom
      dose, and the amount of FabAV injected was 10 times the amount needed for venom
      neutralization. Statistical analysis included Fisher's exact test and log-rank
      testing to compare survival rates and times. RESULTS: The venom LD 50 was found
      in preliminary studies to be 0.9 mg/kg and 1.35 mg/kg for the C durissus
      terrificus venom obtained from Sigma-Aldrich Co. and Biotoxins Inc.,
      respectively. The LD 50 for B atrox venom was 5.0 mg/kg. All animals receiving
      venom only and saline solution died. Animals receiving FabAV together with either
      venom survived to the end of the 24-hour observation period ( P <.001).
      Comparison of survival times between groups demonstrated a significant difference
      in time to death between venom-only control groups and the FabAV+venom groups (P
      <.001). All animals in the FabAV+normal saline solution group survived to the
      conclusion of the study. CONCLUSION: FabAV, when premixed with venom, decreases
      lethality in a murine model of intraperitoneal venom injection of the South
      American pit vipers, C durissus terrificus and B atrox .

PMID- 15940092
TI  - Pressure-immobilization bandages delay toxicity in a porcine model of eastern
      coral snake (Micrurus fulvius fulvius) envenomation.
AB  - STUDY OBJECTIVES: Pressure-immobilization bandages are used in countries where
      neurotoxic snake envenomations are common. They impede lymphatic egress from the
      bite site and delay systemic venom toxicity. The effectiveness of these devices
      has not been evaluated in coral snake envenomations. We investigated the efficacy
      of pressure-immobilization bandages in delaying the onset of systemic toxicity in
      a porcine model of coral snake envenomation. METHODS: A randomized controlled
      trial of pressure-immobilization bandages was conducted in a university animal
      care center. Subjects were 12 anesthetized, spontaneously breathing pigs, ranging
      from 9.1 to 11.4 kg. After injection with 10 mg of Micrurus fulvius fulvius venom
      in the subcutaneous tissue of the distal foreleg, subjects were randomized to
      receive no treatment or application of a pressure-immobilization bandage at 1
      minute after injection. Treated animals had elastic bandages applied to the
      extremity and splinting for immobilization. Vital signs and quality of
      respirations were recorded. Outcome was the onset of respiratory failure or
      survival to 8 hours. Necropsies and histologic analysis of the envenomation site
      was performed. RESULTS: One animal from each group was removed because of the
      discovery of pre-existing respiratory pathology. Four of 5 pigs in the treatment
      group survived to 8 hours, but none in the control group survived. Mean time to
      onset of respiratory compromise was 170.4 +/- 33.3 minutes in the control group.
      None of the pigs had histologic changes at the envenomation site consistent with
      ischemia or pressure-related injury. CONCLUSION: Pressure-immobilization bandages
      delayed the onset of systemic toxicity in our porcine model of M fulvius
      envenomation.

PMID- 15940093
TI  - Tetramethylenedisulfotetramine: old agent and new terror.
AB  - Tetramethylenedisulfotetramine has accounted for numerous intentional and
      unintentional poisonings in China. In May 2002, the first known case of human
      illness in the United States caused by tetramethylenedisulfotetramine, a banned
      neurotoxic rodenticide from China, occurred in New York City. The clinical
      presentation after tetramethylenedisulfotetramine exposure is dose dependent, and
      the most recognized complication is status epilepticus. Poisonings may be fatal
      within hours. No known antidote exists, and treatment is mainly supportive.
      Anecdotal reports, case reports, and 2 animal studies suggest possible success
      with certain pharmacologic interventions, including pyridoxine and chelation
      therapy. Pesticide and rodenticide poisonings, whether intentional or
      unintentional, pose a serious threat to populations, and the availability of a
      banned rodenticide such as tetramethylenedisulfotetramine, with its associated
      morbidity and lethality, is a serious public health concern. Given the recent
      case report that confirms the presence of tetramethylenedisulfotetramine in the
      United States, the toxicity of the compound, its unique physical properties, the
      absence of an antidote, and the history of its use as an agent of intentional
      mass poisoning, public health entities have undertaken educational efforts to
      inform the public, health care providers, and emergency personnel of this
      potentially lethal rodenticide.

PMID- 15940094
TI  - Resuscitative effect of a gamma-aminobutyric acid B receptor antagonist on gamma
      hydroxybutyric acid mortality in mice.
AB  - STUDY OBJECTIVE: In the present study, a number of compounds were tested to
      evaluate their efficacy in exerting a protective effect on gamma-hydroxybutyric
      acid (GHB)-induced mortality in mice. The drugs investigated were the gamma
      aminobutyric acid B (GABA B ) receptor antagonist SCH 50911, the GABA A receptor
      antagonist bicuculline, the benzodiazepine receptor antagonist flumazenil, the
      putative GHB receptor antagonist NCS-382, the opioid receptor antagonist
      naltrexone, and the amino acid and possible neuromodulator, taurine. METHODS: All
      mice were initially treated with a lethal dose of GHB (7 g/kg, administered
      intragastrically). Once mice had displayed clear signs of GHB intoxication,
      animals from each group were treated acutely with either SCH 50911 (vehicle; 75,
      150, and 300 mg/kg, administered intraperitoneally), bicuculline (vehicle; 2, 4,
      6, and 8 mg/kg, administered intraperitoneally), flumazenil (vehicle; 1, 3, and
      10 mg/kg, administered intraperitoneally), NCS-382 (vehicle; 50 and 200 mg/kg,
      administered intraperitoneally), naltrexone (vehicle; 3 and 10 mg/kg,
      administered intraperitoneally), or taurine (vehicle; 250 and 750 mg/kg,
      administered intraperitoneally). The various doses of each single drug were
      administered to 10 mice, randomly allocated throughout the experimental groups.
      Mortality was recorded every hour for the first 9 hours and subsequently 12, 18,
      and 24 hours after GHB injection. RESULTS: In each experiment, all vehicle
      treated mice died within 24 hours of GHB injection. Doses of 150 and 300 mg/kg
      SCH 50911 produced a marked protection on GHB-induced mortality, evidenced by the
      death of only 0 of 10 and 2 of 10 mice in the 150- and 300-mg/kg SCH 50911
      groups, respectively. In contrast, at all doses tested, bicuculline, flumazenil,
      NCS-382, naltrexone, and taurine were not observed to exert any protective effect
      on GHB-induced mortality (9 to 10/10 mice died in each treatment group).
      CONCLUSION: These results suggest an involvement of the GABA B receptor, at least
      in rodents, in the mediation of the lethal effects of GHB.

PMID- 15940095
TI  - Emergency department brief motivational interventions for alcohol with motor
      vehicle crash patients.
AB  - STUDY OBJECTIVE: This study compares the effect of a brief motivational
      intervention for alcohol plus a booster given to emergency department (ED)
      patients with subcritical injuries from a motor vehicle crash with the effect of
      brief motivational intervention for alcohol plus a booster in patients treated
      for non-motor vehicle crash-related injuries. METHODS: A randomized controlled
      trial (n=539) was conducted at an urban Level I trauma center of brief
      intervention (1 ED session of brief intervention), brief motivational
      intervention for alcohol plus a booster (1 ED session plus booster session), or
      standard care for injured ED patients with an alcohol use problem who were being
      discharged home. At 12 months, alcohol-related negative consequences and injuries
      were measured. We performed a secondary analysis comparing motor vehicle crash
      injured patients and non-motor vehicle crash-injured patients in the study
      sample. RESULTS: Subcritically injured ED patients with harmful or hazardous
      alcohol use who received brief motivational intervention for alcohol plus a
      booster had fewer alcohol-related negative consequences and alcohol-related
      injuries than those receiving brief intervention or standard care at 12-month
      follow-up (previously reported). A secondary analysis of this result showed that
      motor vehicle crash patients (n=133) given brief motivational intervention for
      alcohol plus a booster (n=34) had fewer alcohol-related injuries than those
      receiving standard care (n=46; P =.001). Moreover, there were no significant
      differences in alcohol-related injuries among the non-motor vehicle crash-injured
      patients who received brief intervention or standard care. CONCLUSION: Brief
      motivational intervention for alcohol plus a booster is a useful intervention for
      subcritically injured ED patients with harmful or hazardous alcohol use. Its
      effects may be moderated by the cause of injury.

PMID- 15940096
TI  - An observational study of safety belt use among taxi drivers in Boston.
AB  - STUDY OBJECTIVE: Although safety belt legislation exists for drivers in
      Massachusetts, there is an exemption for taxicab drivers. According to the most
      recent data from the Governor's Highway Safety Bureau, the observed safety belt
      use rate of drivers in Massachusetts is 64%. However, the safety belt use among
      taxicab drivers in Boston is unknown. METHODS: An observational study was
      conducted to assess the prevalence of safety belt use among taxicab drivers in
      Boston. We compared our findings with state-level data obtained from the
      Governor's Highway Safety Bureau. Research staff made observations of taxicabs
      arriving at various sites within Boston (Logan Airport, Back Bay subway entrance,
      Government Center, and a hospital in Boston). The methodology used in this study
      was adapted from MASS-Safe, the Traffic Safety Research Program of the Governor's
      Highway Safety Bureau. In brief, research staff assessed the use of shoulder
      safety belts worn by taxicab drivers in Boston. Researchers observed traffic flow
      coming from a single direction at each observation site. These observers were
      instructed to include only taxicabs in motion, approaching in the nearest lane to
      the sidewalk. RESULTS: Two hundred fifty taxicabs were observed during the study
      period. Of these, 247 taxicab drivers were men (98.9%), whereas 3 were women
      (1.2%). Overall, 17 of 250 taxicab drivers (6.8%; 95% confidence interval 3.9% to
      9.7%) wore safety belts, whereas 233 (93.2%) did not. CONCLUSION: The safety belt
      use among taxicab drivers in Boston is 6.8%, markedly lower than the state-level
      safety belt use of other drivers in Massachusetts. Stronger safety belt use
      legislation in Massachusetts may help to improve safety belt use among taxi
      drivers in Boston.

PMID- 15940097
TI  - Non-work-related finger amputations in the United States, 2001-2002.
AB  - STUDY OBJECTIVE: We characterize non-work-related finger amputations treated in
      US hospital emergency departments (EDs) and discuss implications for injury
      prevention programs. METHODS: Finger amputation data from 2001 and 2002 were
      obtained from the National Electronic Injury Surveillance System All Injury
      Program (a nationally representative sample of 66 US hospital EDs). National
      estimates are based on weighted data for 948 cases for finger amputations
      (including partial and complete) that occurred during non-work-related activities
      (ie, nonoccupational) activities. RESULTS: An estimate of 30,673 (95% confidence
      interval [CI] 24,877 to 36,469) persons with non-work-related amputations were
      treated in US hospital EDs annually. Of these persons, 27,886 (90.9%; 95% CI
      22,707 to 33,065) had amputations involving 1 or more fingers; 19.1% were
      hospitalized or transferred for specialized trauma care. Male patients were
      treated for finger amputations at 3 times the rate of female patients. The rate
      of persons treated for finger amputations was highest for children younger than 5
      years (18.8 per 100,000 population; 95% CI 12.3 to 25.2 per 100,000 population),
      followed by adults aged 55 to 64 years (14.9 per 100,000 population; 95% CI 9.6
      to 20.1 per 100,000 population). For children aged 4 years and younger, 72.9%
      were injured in incidents involving doors, and for adults aged 55 years or older,
      47.2% were injured in incidents involving power tools. CONCLUSION: National
      estimates of finger amputations among US residents indicate that young children
      and older adults are at greatest risk. Parents or other responsible adults should
      be aware of the risk of small children's fingers around doorways, and adults
      should take safety precautions when using power tools.

PMID- 15940098
TI  - Hand injury prevention.

PMID- 15940100
TI  - National Highway Traffic Safety Administration(NHTSA) Notes. Graduated driver
      licensing systems.

PMID- 15940101
TI  - Medical treatment of radiological casualties: current concepts.
AB  - The threat of radiologic or nuclear terrorism is increasing, yet many physicians
      are unfamiliar with basic treatment principles for radiologic casualties.
      Patients may present for care after a covert radiation exposure, requiring an
      elevated level of suspicion by the physician. Traditional medical and surgical
      triage criteria should always take precedence over radiation exposure management
      or decontamination. External contamination from a radioactive cloud is easily
      evaluated using a simple Geiger-Muller counter and decontamination accomplished
      by prompt removal of clothing and traditional showering. Management of surgical
      conditions in the presence of persistent radioactive contamination should be
      dealt with in a conventional manner with health physics guidance. To be most
      effective in the medical management of a terrorist event involving high-level
      radiation, physicians should understand basic manifestations of the acute
      radiation syndrome, the available medical countermeasures, and the psychosocial
      implications of radiation incidents. Health policy considerations include
      stockpiling strategies, effective use of risk communications, and decisionmaking
      for shelter-in-place versus evacuation after a radiologic incident.

PMID- 15940102
TI  - When it's hot, it's hot.

PMID- 15940103
TI  - Secondary contamination of emergency department personnel from o
      chlorobenzylidene malononitrile exposure, 2002.
AB  - In a hazardous materials event in 2002, the unannounced presentation of 3
      symptomatic, contaminated patients to an emergency department (ED) resulted in
      secondary contamination of 2 ED personnel who experienced skin, eye, and
      respiratory irritation. The material that caused these injuries was o
      chlorobenzylidene malononitrile, a white powder with a peppery odor used largely
      as a tear gas and riot-control agent. Secondary contamination can cause adverse
      symptoms and injuries in ED personnel, further contaminate the ED, and
      potentially lead to costly ED closures and evacuations. To prevent secondary
      exposure, EDs can educate their staff about the potential for secondary
      contamination, implement a team approach for handling contaminated patients,
      establish decontamination protocols, ensure proper selection of and training in
      the use of personal protective equipment, and simulate drills for receiving
      contaminated patients.

PMID- 15940104
TI  - The model of the clinical practice of emergency medicine: a 2-year update.

PMID- 15940105
TI  - In-Service.

PMID- 15940106
TI  - Images in emergency medicine. Ectopic pregnancy.

PMID- 15940107
TI  - Foreign body in the tongue: a novel use for emergency department ultrasonography.

PMID- 15940108
TI  - Limiting out-of-hospital intubation in the Israel Defense Forces.

PMID- 15940109
TI  - Response to Latrodectus-associated compartment syndrome.

PMID- 15940110
TI  - Femoral nerve block for femur fractures.

PMID- 15940112
TI  - Hospital water point-of-use filtration: a complementary strategy to reduce the
      risk of nosocomial infection.
AB  - Cholera, hepatitis and typhoid are well-recognized water-borne illnesses that
      take the lives of many every year in areas of uncontrollable flood, but far less
      attention is afforded to the allegedly safe potable water in affluent nations and
      the presumed healthful quality of water in communities and hospitals. Recent
      literature, however, points to increasing awareness of serious clinical sequelae
      particularly experienced by immunocompromised patients at high risk for disease
      and death from exposure to water-borne microbes in hospitals. This review
      reflects the literature indicting hospital water as an important source for
      nosocomial infections, examines patient populations at greatest risk, uncovers
      examples of failures in remedial water treatment methods and the reasons for
      them, and introduces point-of-use water filtration as a practical alternative or
      complementary component of an infection control strategy that may reduce the risk
      of nosocomial infections.

PMID- 15940113
TI  - Efficacy of new point-of-use water filter for preventing exposure to Legionella
      and waterborne bacteria.
AB  - BACKGROUND: Legionella species cause health care-acquired infections in which
      immunocompromised patients are disproportionately affected. Epidemiologic studies
      have demonstrated that point-of-use water fixtures are the reservoirs for these
      infections. The current approach to prevention is system-wide chemical
      disinfection of the hospital water system. These methods affect both low-risk and
      high-risk areas. A more effective approach to prevention may be a targeted
      approach aimed at protecting high-risk patients. One option is the application of
      a physical barrier (filter) at the point-of-use water fixture. OBJECTIVES: To
      evaluate the ability of point-of-use filters to eliminate Legionella and other
      pathogens from water. METHODS: One hundred twenty-milliliter hot water samples
      were collected from 7 faucets (4 with filters and 3 without) immediately and
      after a 1-minute flush. Samples were collected every 2 or 3 days for 1 week. This
      cycle was repeated for 12 weeks. Samples were cultured for Legionella, total
      heterotrophic plate count (HPC) bacteria, and Mycobacterium species. RESULTS:
      Five hundred ninety-four samples were collected over 12 cycles. No Legionella or
      Mycobacterium were isolated from the faucets with filters between T = 0 and T = 8
      days. The mean concentration of L pneumophila and Mycobacterium from the control
      faucets was 104.5 CFU/mL and 0.44 CFU/mL, respectively. The filters achieved a
      greater than 99% reduction in HPC bacteria in the immediate and postflush
      samples. CONCLUSIONS: Point-of-use filters completely eliminated L pneumophila
      and Mycobacterium from hot water samples. These filter units could prevent
      exposure of high-risk patients to waterborne pathogens.

PMID- 15940114
TI  - Prevention and control of health care-associated waterborne infections in health
      care facilities.
AB  - The current article is a review of the public health risks attributable to
      waterborne pathogens in health care. The consequences of health care-associated
      infections (HAIs) are discussed. Not only are Legionella spp involved in HAIs,
      but also Pseudomonas aeruginosa, other gram-negative microorganisms, fungi, and
      amoeba-associated bacteria. This is particularly noteworthy among
      immunocompromised patients. New prevention strategies and control measures
      brought about through advanced planning, facility remodelling and reconstruction,
      disinfection, and filtration have resulted in a significant reduction of the
      incidence of waterborne HAIs. The positive consequences of a comprehensive
      multibarrier approach including prevention and control programs in health care
      facilities are discussed. Environmental cultures are now integrated within the
      infection control program of some European countries. In high-risk areas, the
      application of disposable sterile point-of-use filters for faucets and shower
      heads appears to be the practice of choice to efficiently control waterborne
      pathogens and to prevent infections.

PMID- 15940115
TI  - Ecology of Pseudomonas aeruginosa in the intensive care unit and the evolving
      role of water outlets as a reservoir of the organism.
AB  - In spite of the significant changes in the spectrum of organisms causing
      intensive care unit (ICU)-associated infections, Pseudomonas aeruginosa has held
      a nearly unchanged position in the rank order of pathogens causing ICU-related
      infections during the last 4 decades. Horizontal transmissions between patients
      have long been considered the most frequent source of P aeruginosa
      colonizations/infections. The application of molecular typing methods made it
      possible, during the last approximately 7 years, to identify ICU tap water as a
      significant source of exogenous P aeruginosa isolates. A review of prospective
      studies published between 1998 and 2005 showed that between 9.7% and 68.1% of
      randomly taken tap water samples on different types of ICUs were positive for P
      aeruginosa , and between 14.2% and 50% of infection/colonization episodes in
      patients were due to genotypes found in ICU water. Faucets are easily accessible
      for preventive measures, and the installation of single-use filters on ICU water
      outlets appears to be an effective concept to reduce water-to-patient
      transmissions of this important nosocomial pathogen.

PMID- 15940116
TI  - Formulating a risk reduction strategy for waterborne pathogens in hospital water
      systems.

PMID- 15940117
TI  - Performance of various steam sterilization indicators under optimum and sub
      optimum exposure conditions.

PMID- 15940119
TI  - Diet as a risk factor for atopy and asthma.
AB  - It has been hypothesized that decreasing antioxidant (fruit and vegetables),
      increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and
      decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases
      in asthma and atopic disease. Epidemiologic studies in adults and children have
      reported beneficial associations between dietary antioxidants and lipids and
      parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA
      appear to be very complex and might differ between asthma and atopic dermatitis.
      Dietary antioxidants are probably exerting antioxidant and nonantioxidant
      immunomodulatory effects. Dietary lipids exert numerous complex effects on
      proinflammatory and immunologic pathways. It has also been suggested that atopic
      dermatitis is associated with an enzyme defect in lipid metabolism. In spite of
      this, the results of interventional supplementation studies in established
      disease have been disappointing, and there is now increasing interest in the
      possibility that dietary antioxidant and lipid intakes might be important in
      determining expression of disease during pregnancy and early childhood and that
      dietary interventions should be targeted at these groups. It also seems likely
      that there is individual variation in the responses of individuals to lipid, and
      probably antioxidant, supplementation. Further research to determine whether
      dietary intervention can reduce the risk of asthma and atopic disease is
      justified.

PMID- 15940121
TI  - Mechanisms of nutrient modulation of the immune response.
AB  - Lack of adequate macronutrients or selected micronutrients, especially zinc,
      selenium, iron, and the antioxidant vitamins, can lead to clinically significant
      immune deficiency and infections in children. Undernutrition in critical periods
      of gestation and neonatal maturation and during weaning impairs the development
      and differentiation of a normal immune system. Infections are both more frequent
      and more often become chronic in the malnourished child. Recent identification of
      genetic mechanisms is revealing critical pathways in the gastrointestinal immune
      response. New studies show that the development of tolerance, control of
      inflammation, and response to normal mucosal flora are interrelated and linked to
      specific immune mechanisms. Nutrients act as antioxidants and as cofactors at the
      level of cytokine regulation. Protein calorie malnutrition and zinc deficiency
      activate the hypothalamic-pituitary-adrenal axis. Increased circulating levels of
      glucocorticoids cause thymic atrophy and affect hematopoiesis. Chronic
      undernutrition and micronutrient deficiency compromise cytokine response and
      affect immune cell trafficking. The combination of chronic undernutrition and
      infection further weakens the immune response, leading to altered immune cell
      populations and a generalized increase in inflammatory mediators. Obesity caused
      by excess nutrition or excess storage of fats relative to energy expenditure is a
      form of malnutrition that is increasingly seen in children. Leptin is emerging as
      a cytokine-like immune regulator that has complex effects in both overnutrition
      and in the inflammatory response in malnutrition. Because the immune system is
      immature at birth, malnutrition in childhood might have long-term effects on
      health.

PMID- 15940124
TI  - Measurements of exhaled nitric oxide in healthy subjects age 4 to 17 years.
AB  - BACKGROUND: Fractional exhaled nitric oxide (FE NO ) is used in monitoring of
      asthma. OBJECTIVES: The aim of this multicenter study was to establish normal
      values of FE NO and assess feasibility in children with a standardized method and
      equipment approved for clinical use. METHODS: FE NO was measured in healthy
      subjects of 4 to 17 years according to American Thoracic Society guidelines
      (single breath online, exhalation flow 50 mL/s) with a chemiluminescence analyzer
      (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden) in 3 European
      and 2 US centers. Each child performed 3 acceptable nitric oxide measurements
      within 6 attempts and completed an extended International Study of Asthma and
      Allergy in Children questionnaire. RESULTS: Measurement of FE NO was attempted in
      522 children. Four hundred five children completed the study according to the
      protocol. Geometric mean FE NO in 405 children was 9.7 ppb, and the upper 95%
      confidence limit was 25.2 ppb. FE NO increased significantly with age, and higher
      FE NO was seen in children with self-reported rhinitis/conjunctivitis or hay
      fever. The success rate was age-dependent and improved from 40% in the children 4
      years old to almost 100% from the age of 10 years. The repeatability of 3
      approved measurements was 1.6 ppb (95% CI, 1.49-1.64 ppb). CONCLUSION: FE NO in
      healthy children is below 15 to 25 ppb depending on age and self-reported atopy.
      Measurement of FE NO by NIOX is simple and safe and has a good repeatability.
      Feasibility depends on age and may be difficult in the preschool child.

PMID- 15940125
TI  - Internet-based monitoring of asthma: a long-term, randomized clinical study of
      300 asthmatic subjects.
AB  - BACKGROUND: Experience from other fields of internal medicine shows that Internet
      based technology can be used to monitor various diseases. The new technology
      handles complex calculation programs easily, and it is a unique way of
      communicating. These advantages might be used in optimizing the treatment for
      asthmatic subjects because undertreatment is a common problem found in European
      asthmatic subjects. OBJECTIVE: We sought to investigate the outcome of monitoring
      and treatment using a physician-managed online interactive asthma monitoring tool
      and to assess whether the outcome differs from that of monitoring and treatment
      in an outpatient respiratory clinic or in primary care. METHODS: Three hundred
      asthmatic subjects were randomized to 3 parallel groups in a 6-month prospective
      study: (1) Internet-based monitoring (n = 100); (2) specialist monitoring (n =
      100); and (3) general practitioner (GP) monitoring (n = 100). All the patients
      were examined on entry into the study and after 6 months of treatment. RESULTS:
      The treatment and monitoring with the Internet-based management tool lead to
      significantly better improvement in the Internet group than in the other 2 groups
      regarding asthma symptoms (Internet vs specialist: odds ratio of 2.64, P = .002;
      Internet vs GP: odds ratio of 3.26; P < .001), quality of life (Internet vs
      specialist: odds ratio of 2.21, P = .03; Internet vs GP: odds ratio of 2.10, P =
      .04), lung function (Internet vs specialist: odds ratio of 3.26, P = .002;
      Internet vs GP: odds ratio of 4.86, P < .001), and airway responsiveness
      (Internet vs GP: odds ratio of 3.06, P = .02). CONCLUSION: When physicians and
      patients used an interactive Internet-based asthma monitoring tool, better asthma
      control was achieved.

PMID- 15940126
TI  - Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human
      beings.
AB  - BACKGROUND: Animal models of lung inflammation have validated the plasma 16-kd
      Clara cell protein (CC16) as a peripheral marker of the permeability of the
      alveolocapillary barrier. OBJECTIVE: We investigated in human beings whether
      inhaled LPS induced a rise in airways permeability measured by the plasma changes
      in CC16. METHODS: The CC16 was measured in plasma from 15 subjects exposed to LPS
      by inhalation, during which the kinetics and the dose-response relationship of
      LPS-induced CC16 were evaluated. Because LPS-induced response involves
      macrophages activation, the protective effect of oral methylprednisolone was also
      evaluated. RESULTS: An inhalation of 50 microg LPS induced a significant ( P <
      .001) rise in CC16 after 6 hours (from 7.24 [+/-0.68] microg/L to 10.69 [+/-0.99]
      microg/L) that normalized at 24 hours (6.65 [+/-0.33] microg/L). The CC16
      response was dose-related, with the no-response threshold 0.5 microg LPS. A 6-day
      treatment with 20 mg/d methylprednisolone inhibited significantly ( P < .001) the
      CC16 response to 50 microg LPS. CONCLUSION: Exposure to LPS by inhalation in
      healthy subjects induces an intravascular leakage of CC16 that can be blocked by
      corticosteroids. These observations further validate plasma CC16 as a noninvasive
      test of the alveolocapillary barrier permeability.

PMID- 15940127
TI  - Expression of the anaphylatoxin receptors C3aR and C5aR is increased in fatal
      asthma.
AB  - BACKGROUND: The mechanisms leading to death from asthma are not completely
      understood. Recent studies suggest the involvement of the anaphylatoxins C3a and
      C5a, generated during complement activation, and their receptors C3aR and C5aR in
      the pathogenesis of asthma. OBJECTIVE: The aim of our study was to investigate
      the expression of C3aR and C5aR in fatal asthma. METHODS: We analyzed lung tissue
      from 14 subjects who died of asthma (fatal asthma; FA) and 14 subjects who died
      of nonpulmonary causes (controls) and bronchial biopsy specimens from 16 subjects
      with mild intermittent asthma (MIA). C3aR and C5aR expression was evaluated by
      immunohistochemistry, and a semiquantitative analysis of the intensity of
      staining was performed according to a visual analogue scale (score, 0-3).
      RESULTS: C3aR was expressed on airway epithelium, smooth muscle, submucosal, and
      parenchymal vessels. C5aR was expressed on myeloid cells infiltrating the
      submucosa and on airway epithelium. Statistical analysis demonstrated higher
      expression of C3aR on submucosal vessels in FA compared with controls and MIA
      (median [minimum-maximum], controls, 0.24 [0-1.48]; MIA, 0.0 [0-1.00]; FA, 1.56
      [0.13-3]; P = .002). C3aR was also increased on parenchymal vessels in FA
      (controls, 0.56 [0-2.00]; FA, 1.81 [0.5-3]; P = .0004). C5aR expression on airway
      epithelium was increased in FA compared with controls and MIA (controls, 1.25
      [0.25-3]; MIA, 1.00 [0-2.00]; FA, 3.00 [1.13-3.00]; P = .001). CONCLUSION: The
      results of our study suggest a role of complement in FA.

PMID- 15940128
TI  - Analysis of the lineage relationship between mast cells and basophils using the c
      kit D816V mutation as a biologic signature.
AB  - BACKGROUND: Mast cells and basophils share similar morphologic and functional
      properties; however, it is not known whether they are derived from a bilineage
      (basophil/mast cell)-restricted progenitor. OBJECTIVE: To assess whether
      basophils and mast cells are derived from common committed progenitors using the
      c-kit D816V mutation as a biologic signature. METHODS: The D816V c-kit mutation
      found in mast cells of patients with systemic mastocytosis is used as a trackable
      genetic marker to assess the lineage relationship between mast cells and
      basophils. Blood and bone marrow aspirates were collected from 33 consecutive
      patients with mastocytosis with different disease severity. Peripheral blood
      basophils, monocytes and neutrophils were sorted by immunomagnetic beads.
      Presence of the D816V c-kit mutation was analyzed by restriction fragment length
      polymorphism in the genomic DNA and mRNA from sorted cells in all patients and in
      the genomic DNA of individual basophils of 1 patient. RESULTS: The c-kit D816V
      mutation was detectable in basophils of 5 patients (15%). All 5 patients had the
      c-kit mutation also detectable in monocytes and thus had multilineage
      involvement. Single cell analysis of the genomic DNA in 1 patient showed a
      similar degree of clonal expansion in basophils, monocytes, and neutrophils.
      Mutated c-kit was expressed at the mRNA level in all 5 patients. There was no
      difference in surface Kit expression levels in basophils. CONCLUSION: Basophils
      carrying the D816V c-kit mutation in mastocytosis were detected only in the
      context of a multilineage involvement. These results argue against the presence
      of a bilineage-restricted committed progenitor for mast cells and basophils.

PMID- 15940129
TI  - Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung
      mast cell.
AB  - BACKGROUND: MC(T) and MC(TC) types of human mast cells (MCs) are distinguished
      from one another on the basis of the protease compositions of their secretory
      granules, but their functional and developmental relationships have been
      uncertain. OBJECTIVE: These studies better define the functional properties and
      developmental relationship of MC(T) and MC(TC) cells. METHODS: Mast cells were
      dispersed from human skin and lung, purified with anti-Kit antibody, and
      separated into CD88+ and CD88- populations by cell sorting. These cells were
      evaluated by immunocytochemistry with antitryptase and antichymase mAbs; for
      chymase and tryptase mRNA by real-time RT-PCR; for conversion of MC(T) to MC(TC)
      cells during cell culture with recombinant human stem cell factor and recombinant
      human IL-6; and for degranulation and leukotriene C 4 (LTC 4 ) secretion when
      stimulated with anti-FcepsilonRI, substance P, C5a, and compound 48/80. RESULTS:
      Mature MC(T) and MC(TC) cells were separated from one another on the basis of
      selective expression of CD88, the C5aR, on MC(TC) cells. Lung MC(T) cells had
      negligible levels of chymase mRNA and retained their MC(T) phenotype in culture.
      Mature MC(TC) cells from skin and lung degranulated in response to FcepsilonRI
      cross-linking, C5a, compound 48/80, and substance P. Lung MC(TC) cells released
      LTC 4 on activation, but no LTC 4 was detected when skin-derived MC(TC) cells
      were activated. MC(T) cells from lung degranulated and released LTC 4 in response
      to anti-FcepsilonRI and substance P, but not to C5a and compound 48/80.
      CONCLUSION: These observations functionally distinguish MC(T) from MC(TC) types
      of human mast cells and suggest important differences that may affect their
      participation in diseases such as asthma and urticaria.

PMID- 15940130
TI  - Genome screen for asthma and bronchial hyperresponsiveness: interactions with
      passive smoke exposure.
AB  - BACKGROUND: Asthma is a common respiratory disease caused by the interaction of
      genetic susceptibility and exposure to various environmental factors. Passive
      smoke exposure, characterized by parental smoking, has been shown to be a risk
      factor for the development of atopy and asthma. OBJECTIVE: We sought to perform a
      genome-wide linkage screen for asthma and bronchial hyperresponsiveness (BHR) and
      to determine the influence of passive tobacco smoke exposure during childhood on
      the results of genetic linkage studies to investigate gene-environment
      interactions. METHODS: A genome-wide linkage screen for asthma and BHR was
      performed in 200 families ascertained through a parent with asthma. Analyses were
      performed separately for the entire sample and for the smoking-exposed and
      nonexposed families. RESULTS: For asthma and BHR, the strongest evidence for
      linkage was observed for chromosomes 3p and 5q. The families in which the
      children were exposed to passive smoking accounted for the evidence for linkage
      of BHR to 5q ( P < .001), but evidence for linkage to 3p was found in both sets
      of families. Similar results were observed for asthma. However, there was no
      observed difference in the frequency of asthma or BHR in the offspring from the
      smoke-exposed compared with the nonexposed families. CONCLUSION: The results from
      this study demonstrate that the influence of susceptibility genes for a common
      disease such as asthma might not be apparent unless there is the appropriate
      exposure to environmental stimuli, such as passive exposure to cigarette smoke.
      This approach should be useful for identification of asthma susceptibility genes.

PMID- 15940131
TI  - Soy, isoflavones, and prevalence of allergic rhinitis in Japanese women: the
      Osaka Maternal and Child Health Study.
AB  - BACKGROUND: It has been hypothesized that isoflavones reduce the risk of many
      chronic diseases, but there are no data on the effects of dietary soy and
      isoflavone consumption on allergic disorders. OBJECTIVE: This cross-sectional
      study examined the relationship between dietary soy products and isoflavone
      intake and the prevalence of allergic rhinitis. METHODS: Study subjects were 1002
      Japanese pregnant women. Allergic rhinitis (including cedar pollinosis) was
      defined as present if subjects had received drug treatment at some point during
      the previous 12 months. Adjustment was made for age; gestation; parity; cigarette
      smoking; passive smoking at home and at work; indoor domestic pets; family
      history of asthma, atopic eczema, and allergic rhinitis; family income;
      education; mite allergen level in house dust; changes in diet in the previous
      month; season when data were collected; and body mass index. RESULTS: Compared
      with dietary intake of total soy product, soy protein, daidzein, and genistein in
      the first quartile, consumption of these substances in the fourth quartile was
      independently associated with a reduced prevalence of allergic rhinitis, although
      no significant dose-response relationships were observed. A clear inverse linear
      trend for miso intake across quartiles was found, whereas the adjusted odds ratio
      for comparison of the highest with the lowest quartile was not statistically
      significant. Consumption of tofu, tofu products, fermented soybeans, boiled
      soybeans, and miso soup was not related to the prevalence of allergic rhinitis.
      CONCLUSION: A high intake of soy and isoflavones may be associated with a reduced
      prevalence of allergic rhinitis.

PMID- 15940132
TI  - Clinical, functional, and immunologic effects of sublingual immunotherapy in
      birch pollinosis: a 3-year randomized controlled study.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) has been proved effective in allergic
      rhinitis, but there are few studies assessing its effects on inflammation and on
      the lower airways. OBJECTIVE: We sought to evaluate at the same time the effects
      of SLIT on rhinitis symptoms, nasal inflammation, and lower airways function in
      patients with birch pollinosis. METHODS: Adult patients with rhinitis and asthma
      monosensitized to birch were evaluated during a run-in pollen season and then
      randomized to receive openly either drugs alone or drugs plus SLIT and
      reevaluated in the subsequent 4 pollen seasons. Rhinitis symptoms and consumption
      of bronchodilators were assessed by means of diary card. A nasal smear for
      eosinophil count was carried out in and out of pollen seasons, and pulmonary
      function tests with methacholine challenge were performed at each season.
      RESULTS: Of 79 enrolled patients, 27 dropped out, with a significantly higher
      rate of dropouts in the control group. There was a decrease in symptoms and
      bronchodilator use in the SLIT group versus the control group, becoming
      significant at the second and third pollen seasons, respectively ( P < .01 at all
      times). Nasal eosinophils decreased significantly in the active group, starting
      from the third pollen season ( P < .01). In the SLIT group a significant increase
      in FEV 1 , specific airways conductance, and maximal expiratory flow at 25% of
      forced vital capacity was seen starting from the second year and was associated
      with an increase in the methacholine threshold dose ( P < .01). The differences
      were significant also at the intragroup comparison over time. CONCLUSION: SLIT
      achieved a significant clinical benefit in birch pollinosis, reduced the
      eosinophil infiltration in nasal mucosa, and significantly improved pulmonary
      function during the pollen seasons.

PMID- 15940134
TI  - Advances in environmental and occupational diseases 2004.
AB  - 2004 was another good year for publications on environmental and occupational
      disorders in our journal. The major focus is clearly on the environment and
      particularly on environmental risk factors for sensitization and asthma. There is
      a growing consensus that exposure to pets is good, provided there is enough of
      it. Low levels enhance sensitization, and higher levels protect against the
      consequences of that sensitization. Following on from previous work on
      cockroaches, we now see allergy to feral mice as an emergent problem--at least we
      now have the tools to study this properly. Emphasis seems to be swinging away
      from the outdoor environment as a cause of allergic disease and toward the indoor
      environment, which is, after all, where most of us spend most of our lives. New
      techniques for studying isocyanate allergy might kindle a revival of interest in
      the mechanisms of occupational asthma caused by low-molecular-weight compounds.
      But for all types of occupational allergy, prevention remains key, and it is good
      to see that comprehensive programs of allergen reduction can pay off in reduced
      rates of latex allergy in health care workers. Further work in the area of
      recombinant allergens is welcome but needs soon to be translated into new
      diagnostic and therapeutic strategies. This sector of allergy research remains
      vibrant, and the editors will continue to welcome outstanding contributions in
      this area.

PMID- 15940133
TI  - Prostaglandin, leukotriene, and lipoxin balance in chronic rhinosinusitis with
      and without nasal polyposis.
AB  - BACKGROUND: Upper airway diseases and especially the aspirin hypersensitivity
      syndrome have been linked to changes in the arachidonic acid cascade; however,
      the specificity of these changes and their relation to inflammatory reactions in
      these diseases still remain controversial. OBJECTIVE: We aimed to study the
      tissue eicosanoid production in 3 subgroups of patients with chronic
      rhinosinusitis (CRS) and control subjects and to correlate it with the severity
      of inflammation and clinical manifestation of aspirin sensitivity. METHODS:
      Samples were prepared from sinonasal tissue of patients with CRS with (CRS-NP
      group, n = 13) and without nasal polyposis (CRS group, n = 11), sinonasal tissue
      of patients with nasal polyposis and aspirin sensitivity (CRS-ASNP group, n =
      13), and normal nasal mucosa from healthy subjects (NM group, n = 8). Real-time
      PCR was applied for mRNA quantification of COX-2, 5-lipoxygenase, leukotriene C 4
      synthase, and 15-lipoxygenase. Enzyme immunoassays were used to measure IL-5,
      eosinophil cationic protein, and eicosanoid (leukotriene [LT] C 4 , LTD 4 , and
      LTE 4 ; lipoxin A 4 ; and prostaglandin E 2 [PGE 2 ]) concentrations. RESULTS:
      COX-2 mRNA and PGE 2 concentrations were similar in the CRS and NM groups but
      significantly decreased in nasal polyp tissue, especially in the CRS-ASNP group.
      LTC 4 synthase, 5-lipoxygenase mRNA, LTC 4 , LTD 4 , and LTE 4 concentrations
      increased with disease severity among the patient groups. 15-Lipoxygenase and
      lipoxin A 4 concentrations were increased in all CRS groups compared with in the
      NM group but were significantly downregulated in the CRS-ASNP group when compared
      with the CRS-NP group. IL-5 and eosinophil cationic protein were increased in
      both groups of nasal polyp tissue compared with in the NM and CRS groups and
      correlated directly with LTC 4 , LTD 4 , and LTE 4 concentrations and inversely
      with PGE 2 concentrations. CONCLUSION: Changes of tissue eicosanoid metabolism do
      occur in CRS, even in the absence of clinical aspirin sensitivity, and these
      changes appear to be related to the severity of eosinophilic inflammation.

PMID- 15940135
TI  - Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the
      Barbados Asthma Genetics Study.
AB  - BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C
      260T) and exposure to endotoxin are believed to play key roles in modulating the
      immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate
      the role of the CD14 C-260T polymorphism in a population of African descent and
      to test for interaction between this genotype and house dust endotoxin (HDE)
      exposure on atopic phenotypes. METHODS: Asthmatic probands and their families
      were recruited as part of the Barbados Asthma Genetics Study. The C-260T
      polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were
      genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family
      Based Association Test, the C-260T allele appeared to be protective against
      asthma ( z = -2.444; P = .015) and asthma severity ( z = -2.615; P = .009) under
      a recessive model. No significant associations were observed for the G-1461T and
      C-1721T markers both individually and in haplotypes. In a case-control analysis,
      the CD14 TT genotype was found to reduce risk of asthma compared with the CD14
      CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated
      with lower asthma severity scores ( P < .002). The TT genotype might protect
      against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but
      may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03
      131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest
      that the CD14-260 polymorphism may play a role in controlling risk to atopic
      disease and underscore the importance of incorporating key environmental
      exposures into studies of genetic risk factors.

PMID- 15940136
TI  - Diagnosis of Alternaria alternata sensitization with natural and recombinant Alt
      a 1 allergens.
AB  - BACKGROUND: Diagnosis of Alternaria alternata sensitization is hampered by the
      variability and complexity of fungal extracts, and thus simplification of the
      diagnostic procedures with purified allergens should be pursued. OBJECTIVE: We
      sought to compare A alternata extract and purified natural Alt a 1 (nAlt a 1) and
      recombinant Alt a 1 (rAlt a 1) allergens for their diagnostic value. METHODS:
      Forty-two patients allergic to A alternata , 10 atopic patients with negative
      skin prick test responses to A alternata extract, and 10 healthy subjects were
      investigated. Skin prick tests and determination of specific IgE levels were
      performed with nAlt a 1 and 2 different types of rAlt a 1: rbAlt a 1, expressed
      in Escherichia coli , and ryAlt a 1, expressed in the yeast Yarrowia lipolytica .
      RESULTS: Prevalence for Alt a 1, Alt a 2, and Alt a 11 by IgE dot-blot testing
      was 98%, 0%, and 15%, respectively, and therefore Alt a 1 was used as a marker
      for A alternata sensitization. Immunoblotting and inhibition analysis showed no
      IgE-binding differences between nAlt a 1 and rAlt a 1. The whole group of
      patients with allergy to A alternata had positive skin test reactions to purified
      allergens at 100 microg/mL, whereas no false-positive reactions were detected.
      Natural or ryAlt a 1 elicited a similar response in skin tests compared with A
      alternata extract, although a reduced reactivity was observed with rbAlt a 1.
      Specific IgE levels to nAlt a 1 or rAlt a 1 showed significant correlation and
      similar sensitivity and specificity. CONCLUSIONS: Alt a 1, either in its natural
      or recombinant form, is sufficient for a reliable diagnosis of A alternata
      sensitization and induces skin prick reactivity comparable with that produced by
      A alternata extract.

PMID- 15940137
TI  - Antibiotic exposure in early infancy and risk for childhood atopy.
AB  - BACKGROUND: The increase in pediatric allergy and asthma parallels the increase
      in use of antibiotics. Antibiotics disturb the flora of the gastrointestinal
      tract, possibly perturbing the developing immune system. OBJECTIVE: We evaluated
      whether antibiotic use during early infancy increased the risk for atopy.
      METHODS: Antibiotic prescriptions documented in medical records were collected
      from a birth cohort born from 1987 through 1989 (n = 725). At 6 to 7 years of
      age, 448 were followed by means of examination, including skin prick tests and
      serum IgE measurements to common allergens. RESULTS: Adjusted odds ratios (aORs)
      and 95% CIs were calculated comparing children with any versus those with no
      antibiotic use in the first 6 months and the outcomes of atopy (any positive skin
      test response), seroatopy (any positive specific IgE test result), either atopy
      or seroatopy, and both atopy and seroatopy. Atopy increased with antibiotic use
      approaching statistical significance (aOR, 1.48; 95% CI, 0.94-2.34; P = .09);
      however, the risk was concentrated among children with less than 2 pets in the
      home (aOR, 1.73; 95% CI, 1.07-2.80; P = .024) and children breast-fed for 4 or
      more months (aOR, 3.02; 95% CI, 1.27-7.17; P = .013). The aORs were generally in
      the same direction for seroatopy and the combined categories. CONCLUSION:
      Antibiotic use in early life appears to contribute to increased risk for atopy in
      certain subgroups of children.

PMID- 15940138
TI  - Challenges in asthma patient education.

PMID- 15940139
TI  - The ethics of placebo-controlled trials: the case of asthma.
AB  - Some have argued that placebo-controlled trials (PCTs) are unnecessary and
      unethical in conditions such as asthma for which there is standard therapy. This
      article, by using asthma clinical trials as an example, examines the ethics of
      PCTs. There remain several scientifically sound reasons to conduct PCTs: (1)
      ensuring scientific validity of the trial, (2) evaluating new therapies less
      effective than the gold standard, (3) minimizing the number of patients exposed
      to potentially inefficacious or dangerous therapy, (4) studying clinical
      situations in which withdrawal of therapy might be considered, and (5)
      determining the true incidence of side effects. Opponents of PCTs err by
      conflating clinical research with clinical practice and ignoring the fact that
      all clinical research involves some sacrifice on the part of the subject for the
      ends of the research and the good of future patients. PCTs do not per se violate
      major ethical codes. Properly conducted, PCTs remain a valuable and ethical tool
      in the armamentarium of modern scientific medicine.

PMID- 15940140
TI  - Diet and allergy: you are what you eat?

PMID- 15940141
TI  - The role of breast-feeding in the development of allergies and asthma.
AB  - Breast-feeding is the preferred method of infant nutrition for numerous reasons.
      However, its role in the prevention of allergic disease remains controversial.
      Reasons for this controversy include methodological differences and flaws in the
      studies performed to date, the immunologic complexity of breast milk itself and,
      possibly, genetic differences among patients that would affect whether breast
      feeding is protective against the development of allergies or is in fact
      sensitizing. The preponderance of evidence does suggest, however, that there
      would be much to lose by not recommending breast-feeding. In general, studies
      reveal that infants fed formulas of intact cow's milk or soy protein compared
      with breast milk have a higher incidence of atopic dermatitis and wheezing
      illnesses in early childhood. Consistent with these findings, exclusive breast
      feeding should be encouraged for at least 4 to 6 months in infants at both high
      and low risk of atopy and irrespective of a history of maternal asthma.

PMID- 15940142
TI  - Report of the Topical Calcineurin Inhibitor Task Force of the American College of
      Allergy, Asthma and Immunology and the American Academy of Allergy, Asthma and
      Immunology.

PMID- 15940143
TI  - Induction of inflammation as a possible mechanism of probiotic effect in atopic
      eczema-dermatitis syndrome.
AB  - BACKGROUND: The immunomodulating mechanisms of Lactobacillus GG (LGG) and other
      probiotics are poorly understood. OBJECTIVE: We studied in vivo the immunologic
      effects of probiotics in infants with atopic eczema-dermatitis syndrome (AEDS)
      and cow's milk allergy (CMA). METHODS: Two hundred thirty infants with AEDS and
      suspected CMA received, concomitant with elimination diet, either LGG, a mixture
      of 4 probiotic strains (MIX), or placebo for 4 weeks. All available paired
      pretreatment and posttreatment plasma samples (n = 132) were analyzed for
      concentrations of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma, soluble
      intercellular adhesion molecule 1, soluble E-selectin, TGF-beta1, TGF-beta2, and
      C-reactive protein. RESULTS: In infants with IgE-associated AEDS, treatment with
      LGG induced higher C-reactive protein levels than in the placebo group (geometric
      mean, 0.83 microg/mL [95% CI, 0.56-0.81] vs 0.42 microg/mL [95% CI, 0.27-0.65]; P
      = .021). Concomitantly, IL-6 levels increased after treatment with LGG ( P =
      .023) but not with MIX or placebo. Soluble E-selectin levels were higher after
      probiotic than after placebo treatment in infants with IgE-mediated CMA (LGG
      geometric mean, 86.7 ng/mL [95% CI, 75.2-100]; MIX geometric mean, 91.6 ng/mL
      [95% CI, 74.8-111.9]; and placebo geometric mean, 64.9 ng/mL [95% CI, 53-79.3];
      analysis of covariance, P = .035; LGG vs placebo, P = .023; MIX vs placebo, P =
      .020). Use of MIX induced an increase in plasma IL-10 levels ( P = .016).
      CONCLUSION: Probiotics induced systemically detectable low-grade inflammation,
      which might explain the clinical effects of probiotics in AEDS and CMA.

PMID- 15940144
TI  - Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro
      by modulating dendritic cell function through dendritic cell-specific
      intercellular adhesion molecule 3-grabbing nonintegrin.
AB  - BACKGROUND: Lactobacilli are probiotic bacteria that are frequently tested in the
      management of allergic diseases or gastroenteritis. It is hypothesized that these
      probiotics have immunoregulatory properties and promote mucosal tolerance, which
      is in part mediated by regulatory T cells (Treg cells). On the basis of
      pathogenic or tissue-specific priming, dendritic cells (DC) acquire different T
      cell-instructive signals and drive the differentiation of naive T H cells into
      either T H 1, T H 2, or regulatory effector T cells. OBJECTIVE: We studied in
      what way different species of lactobacilli prime human DCs for their ability to
      drive Treg cells. METHODS: Human monocyte-derived DCs were cultured in vitro with
      lactobacilli of different species. RESULTS: Two different species of
      lactobacilli, Lactobacillus reuteri and Lactobacillus casei , but not
      Lactobacillus plantarum, prime monocyte-derived DCs to drive the development of
      Treg cells. These Treg cells produced increased levels of IL-10 and were capable
      of inhibiting the proliferation of bystander T cells in an IL-10-dependent
      fashion. Strikingly, both L reuteri and L casei , but not L plantarum , bind the
      C-type lectin DC-specific intercellular adhesion molecule 3-grabbing non-integrin
      (DC-SIGN). Blocking antibodies to DC-SIGN inhibited the induction of the Treg
      cells by these probiotic bacteria, stressing that ligation of DC-SIGN can
      actively prime DCs to induce Treg cells. CONCLUSIONS: The targeting of DC-SIGN by
      certain probiotic bacteria might explain their beneficial effect in the treatment
      of a number of inflammatory diseases, including atopic dermatitis and Crohn's
      disease.

PMID- 15940146
TI  - Brain-derived neurotrophic factor is increased in atopic dermatitis and modulates
      eosinophil functions compared with that seen in nonatopic subjects.
AB  - BACKGROUND: Recently, the pivotal role of brain-derived neurotrophic factor
      (BDNF) has been described in allergic asthma. However, the role of this
      neurotrophin in atopic dermatitis (AD) still remains unknown. OBJECTIVE: The aim
      of this study was to investigate the functional role of BDNF on eosinophils and
      to assess BDNF levels in patients with AD and nonatopic control subjects. Methods
      p75 Neurotrophin receptor and tyrosine kinase B receptor expression was
      demonstrated by using FACS analysis and immunohistochemistry. BDNF levels were
      assessed with ELISA and FACS analysis. Chemotactic activity (modified Boyden
      chamber assay), eosinophil cationic protein release (fluoroenzyme immunoassay),
      respiratory burst (lucigenin-dependent chemiluminescence), and apoptosis
      (Nicoletti protocol and Annexin-V method) assays were used to assess BDNF
      functional activity. RESULTS: BDNF levels were increased in serum, plasma,
      eosinophils, and supernatants of stimulated eosinophils from patients with AD
      compared with levels seen in nonatopic control subjects ( P < .05-.001). In
      addition, p75 neurotrophin receptor and tyrosine kinase B expression was higher
      on eosinophils from patients with AD compared with that seen on eosinophils from
      nonatopic control subjects ( P < .05-.001). Eosinophil apoptosis was inhibited by
      BDNF ( P < .05-.01) and chemotactic index was increased ( P < .001) in BDNF
      stimulated eosinophils from patients with AD, whereas this effect was not shown
      in eosinophils from nonatopic control subjects. However, no response of BDNF
      through the release of eosinophil cationic protein or reactive oxygen species was
      found. CONCLUSION: This study provides the first evidence for a functional role
      of BDNF on eosinophils from patients with AD, probably mediated by an increased
      expression of BDNF receptors compared with that seen in nonatopic control
      subjects. In addition, higher intracellular, serum, and plasma BDNF levels, as
      well as the release of BDNF by eosinophils, underline the particular importance
      of BDNF in patients with AD, pointing to new pathophysiologic aspects of this
      chronic inflammatory skin disease.

PMID- 15940147
TI  - Pimecrolimus leads to an apoptosis-induced depletion of T cells but not
      Langerhans cells in patients with atopic dermatitis.
AB  - BACKGROUND: Apart from the long-used corticosteroids, topical calcineurin
      inhibitors (tacrolimus, pimecrolimus) represent novel therapeutic options for the
      treatment of atopic dermatitis. OBJECTIVE: This study was designed to investigate
      the pathophysiological target cells and mode of action of pimecrolimus in atopic
      skin. METHODS: Twenty-two patients were randomly assigned to treatment with
      pimecrolimus cream 1%, matching vehicle cream, or beta-methasone-17-valerate
      (BMV) cream 0.1% in a randomized, double-blind, vehicle-controlled, parallel
      group clinical trial. Treatment was given twice daily for 3 weeks. Cryostat
      sections of skin biopsies were taken before as well as at selected time points
      after initiation of therapy. For certain experiments, healthy volunteers were
      topically treated with the creams described twice a day on 5 consecutive days.
      Epidermal sheets were prepared from suction blisters. For in vitro experiments,
      untreated, healthy human skin was obtained from patients undergoing plastic
      surgery. The effect of pimecrolimus and BMV on Langerhans cells (LCs),
      inflammatory dendritic epidermal cells, and T cells was investigated by using
      immunofluorescence and flow-cytometry techniques. RESULTS: While topical BMV
      treatment depleted LCs in healthy and atopic skin, pimecrolimus did not affect
      their number. Correlating with the disappearance of inflammatory cells, we
      observed a depletion of inflammatory dendritic epidermal cells and T cells on
      pimecrolimus and BMV treatment. Furthermore, we show that pimecrolimus depletes T
      cells by the induction of apoptosis. CONCLUSION: In summary, our data show that
      pimecrolimus reduces pathological T cells in atopic dermatitis skin via
      apoptosis, whereas LCs remain unaffected.

PMID- 15940148
TI  - Ana o 3, an important cashew nut (Anacardium occidentale L.) allergen of the 2S
      albumin family.
AB  - BACKGROUND: Cashew nut allergy is the second most commonly reported tree nut
      allergy in the United States. We have previously cloned and characterized major
      cashew allergens belonging to the vicilin and legumin families of seed storage
      proteins. OBJECTIVE: Here we set out to describe a third major cashew allergen, a
      2S albumin. METHODS: The recombinant cashew 2S albumin was amplified from a cDNA
      library by means of PCR, sequenced, and expressed in Escherichia coli.
      Immunoblotting was used to screen for reactivity with patients' sera, and
      inhibition immunoblotting was used to identify the corresponding native cashew
      nut proteins. The mass of affinity-purified native allergen was determined by
      means of matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)
      mass spectroscopy. Patients' sera were used to probe solid-phase 2S albumin
      peptides to identify linear epitopes. RESULTS: The cloned allergen, designated
      Ana o 3, was identified as 2S albumin. MALDI-TOF mass spectroscopy of native Ana
      o 3 yielded a molecular mass of 12,598 d. Immunoblot analysis showed 21 (81%) of
      26 sera from patients with cashew allergy were reactive. Three native Ana o 3
      large-subunit isoforms with molecular weights ranging from approximately 6 to 10
      kd were identified. Probing of overlapping synthetic Ana o 3 peptides with
      patients' sera identified 16 reactive peptides, 4 of which gave strong signals
      and one of which positionally overlaps linear epitopes in mustard and walnut
      allergenic 2S albumins. The overlapping cashew and walnut epitopes also share
      considerable homology. CONCLUSIONS: We conclude that this 2S albumin protein is a
      major allergen in cashew nut and demonstrates a possible basis for cross
      reactivity with walnut 2S albumin.

PMID- 15940149
TI  - Diagnosing peanut allergy with skin prick and specific IgE testing.
AB  - BACKGROUND: Food allergy is common in childhood. It has been suggested that the
      magnitude of a skin prick test or specific IgE result can improve diagnostic
      usefulness, but this has been addressed in only a few tertiary challenge-based
      studies. OBJECTIVE: To determine the predictive value of a wheal > or = 8 mm or
      serum specific IgE > or = 15 kU A /L for clinical allergy and investigate whether
      results are generalizable. METHODS: All subjects, up to 16 years of age, who had
      been investigated with a peanut or tree nut food challenge were eligible for the
      study. Subjects were referred from either a tertiary allergy clinic or a
      community birth cohort. All subjects with a history suggestive of food allergy
      were offered a challenge unless there were features of anaphylaxis. Details of
      challenges were prospectively recorded. Results were modeled by using logistic
      regression. RESULTS: There was a total of 161 peanut challenges. Recent skin
      prick (longest wheal diameter) and specific IgE data were available for 135 and
      136 challenges, respectively. The results suggest that a skin prick result > or =
      8 mm and a specific IgE > or = 15 kU A /L have predictive values of 95% (95% CI,
      76.2% to 99.9%) and 92.0% (74.0% to 99.0%), respectively, for a positive
      challenge. Age, the type of nut, and referral pattern of the subject did not
      appear to alter this relationship. CONCLUSION: These data suggest that a skin
      prick result > or = 8 mm or a specific IgE > or = 15 kU A /L have a high
      predictive value for clinical allergy to peanut and that these cutoff figures
      appear generalizable to different populations of children undergoing an
      assessment for peanut allergy.

PMID- 15940150
TI  - Effects of radiation and latent virus on immune responses in a space flight
      model.
AB  - BACKGROUND: The immunosuppressive effects of space flight radiation and
      reactivation of latent virus infections in human beings are largely unknown.
      OBJECTIVE: To develop a murine model that can predict the adverse effects of
      space flight radiation and reactivation of latent virus infection for human
      beings. METHODS: In experiment I, some BALB/c mice received whole-body gamma
      irradiation (3 Gy) on day 0 and murine polyoma virus (PyV) on day 1. In
      experiment II, mice received irradiation (3 Gy) or none on days 0 and/or 49, and
      PyV or none on day 1: A1, 3 Gy/PyV/3 Gy; A2, 3 Gy/ PyV/0 Gy; B1, 0 Gy/PyV/3 Gy;
      B2, 0 Gy/ PyV/0 Gy; C, 3 Gy/0 PyV/0 Gy; and D, 0 Gy/0 PyV/0 Gy. RESULTS: In
      experiment I, PyV was detected by PCR more frequently in several host organs
      tested and for a longer period of time in irradiated than in control animals. In
      experiment II, PyV replication in the spleen was detected in A1>B1 mice on days
      10 and 20; both groups cleared PyV by day 49. After irradiation on day 49,
      reactivated PyV was detected in more B1 than A1 mice. A1 mice had lower spleen
      weights and cell counts than other groups at all time points. From 0 to 49 days,
      irradiation suppressed spleen cell proliferation to concanavalin A in all
      irradiated groups except in B1 when the virus was cleared at day 20. PyV enhanced
      IFN-gamma production in all groups: B1>A1>C, D (0-49 days; all differences, P <
      .05). CONCLUSION: This small animal model of space flight suggests that the
      combined effects of radiation and virus replication will significantly affect T
      lymphocyte-mediated immunity that may lead to chronic viral infection and
      malignancy.

PMID- 15940151
TI  - Neonatal immune responses to microbial stimuli: is there an influence of maternal
      allergy?
AB  - BACKGROUND: Environmental factors are believed to play a role in the development
      of atopic allergy. This is likely to be important very early in life, at the
      fetal stage. The in utero environment could be affected by maternal allergy and
      in turn could influence the immune system of the baby. OBJECTIVE: To investigate
      how cord blood mononuclear blood cells (CBMCs) from children of women with and
      without allergy respond to microbial stimuli. METHODS: PBMCs from women with (n =
      9) and without allergy (n = 10) and CBMCs from their newborn babies were
      stimulated in vitro with LPS and peptidoglycan. Cells were analyzed with flow
      cytometry for expression of CD14, Toll-like receptor (TLR)-2, and TLR4. The
      release of cytokines and chemokines (IL-1beta, IL-6, IL-8, IL-10, IL-12p70, TNF
      alpha) and soluble CD14 into culture supernatants was measured with Cytometric
      Bead Array and ELISA, respectively. RESULTS: Cord blood (CB) monocytes from
      children with mothers with allergy had significantly lower expression of TLR2 and
      TLR4 compared with maternal monocytes both before and after microbial
      stimulation, in contrast with CB monocytes from children with mothers without
      allergy. Further, CBMCs from children with mothers with allergy had a lower ( P =
      .03) IL-6 response after stimulation with peptidoglycan than CBMCs from children
      with mothers without allergy. CONCLUSION: Our results imply that CB monocytes and
      CBMC immune responses are influenced by maternal allergy. On the basis of these
      findings, we speculate that monocytes from children with mothers with allergy
      have a reduced capacity to respond to microbial stimuli.

PMID- 15940153
TI  - Detection of novel latex allergens associated with clinically relevant allergy to
      plant-derived foods.

PMID- 15940152
TI  - Human metapneumovirus infection in children hospitalized for wheezing.

PMID- 15940154
TI  - Importance of mixture of minor determinants and benzylpenicilloyl poly-L-lysine
      skin testing in the diagnosis of beta-lactam allergy.

PMID- 15940155
TI  - Level of osteopontin is increased after bee venom immunotherapy.

PMID- 15940156
TI  - Common variable immunodeficiency presenting with a large abdominal mass.

PMID- 15940157
TI  - Largess, excess, and tithing.

PMID- 15940158
TI  - Does absorption across the buccal mucosa explain early onset of food-induced
      allergic systemic reactions?

PMID- 15940160
TI  - Is randomization of breast-feeding feasible?

PMID- 15940161
TI  - On the hygiene hypothesis: regulation down, up, or sideways?

PMID- 15940162
TI  - Safety of penicillin administration to patients with histories of penicillin
      allergy.

PMID- 15940170
TI  - [Treatment of a burn stricture of the esophagus complicated with a fistula].
AB  - The experience in the treatment of esophageal fistulas is analyzed. Necessity and
      expediency of bougienage of esophageal burn stricture in patients with fistulas
      are discussed, indications and contraindications to bougienage of esophageal
      stricture complicated with a fistula are formulated. Surgical treatment of these
      patients (disfunction of esophageal fistulas and different variants of
      esophagoplasty) are considered.

PMID- 15940171
TI  - [Principles of determination of surgical policy in general peritonitis].
AB  - Based on clinical examination and analysis of treatment results of 575 patients
      with general peritonitis, the most informative factors were determined which
      predict lethal outcome, progression of peritonitis and help choose the most
      effective surgical policy. It is demonstrated that conventional treatment is
      preferable in the interval of perioperative score of APACHE II from 0 to 10, and
      programmed sanation relaparotomies -- from 11 to 15. Data about efficacy of total
      intestinal decompression and peritoneal-enteral lavage, and also methods of
      mathematical prediction of postoperative complications and outcomes are
      presented. Prognostic value of individual symptoms, different degree of organs
      dysfunction and SIRS criteria in early postoperative period were determined.

PMID- 15940172
TI  - [Enterosorption with pectin-containing medication in the treatment of
      peritonitis].
AB  - One hundred and fifty patients aged 19 to 86 years with general peritonitis
      mainly in a toxic (85.3%) stage were examined. The leading causes of peritonitis
      were acute appendicitis (24.0%) and perforation of gastroduodenal ulcers (21.3%).
      Three groups of patients were formed with a pair samples method for a comparative
      analysis of treatment RESULTS: The control group of patients was treated
      conventionally. Entero-sorption was performed through naso-intestinal tube with
      well-known carbonic sorbent UAO-A and pectin-containing medication made of red
      beet. The results were compared. A 1.3-fold decrease in entero-paresis naso
      intestinal intubation duration, a relief in severity of the patients' condition
      by SAPS scale as early as on day 2, improvement of immunity indices, faster
      reduction of toxicity of blood plasma and leukocytic index of intoxication, a 12%
      decrease in postoperative pneumonia morbidity and postoperative lethality from 14
      to 6.6% demonstrated advantages of entero-sorption with pectin-containing
      medication.

PMID- 15940173
TI  - [Diagnosis of chronic duodenal obstruction].
AB  - Arteriomesenterial compression (AMC) of a low-horizontal part of the duodenum is
      one of the causes of chronic duodenal obstruction (CDO). The degree of
      compression of this part of the duodenum was studied in 82 patients with CDO. It
      was revealed that distance between the aorta and superior mesenterial artery
      (SMA) on the level of low-horizontal part of the duodenum was less than 20 mm in
      the majority of cases. When this distance is 20 mm or less the duodenum is
      compressed by SMA and looks like sand-glass. If the distance between the aorta
      and SMA is 10 mm and less, delay of contrast in the middle third of a low
      horizontal part of the duodenum during roentgenography is an obligate symptom. In
      AMC 10-20 mm this phenomenon is diagnosed less frequently. In AMC 20 mm and less
      endoscopy demonstrates symptoms of CDO in the majority of cases. There were no
      intraoperative subjective symptoms of AMC.

PMID- 15940174
TI  - [The role of endoscopy in diagnosis and treatment of gastroduodenal bleedings].
AB  - The experience in diagnosis and treatment of 469 patients with gastroduodenal
      ulcer bleedings is presented. Sensitivity of endoscopy in detection of bleeding
      source was 98.8%, in detection of ulcer size -- 93.4%, specificity -- 80.6%. It
      is demonstrated that the most frequently recurrence of bleeding occurs when ulcer
      size is more than 1 cm. Location of ulcer on posterior, posterior-superior and
      posterior-inferior walls of the duodenal bulb is an unfavorable prognostic
      symptom (rebleeding occurs in 17.1, 30.0 and 12.5% cases, respectively). Types
      Forrest-Ia and Forrest-IIa are especially dangerous for recurrence (21.4 and
      15.6%, respectively). In types Forrest-Ib and Forrest-IIb rebleeding occurs less
      frequently (4 and 6%, respectively). In types Forrest-Ia and Forrest-Ib
      rebleeding occurs mainly on the first day, rebleeding in types Forrest-IIa occurs
      more often on the first-second day, however it is possible up to day 7.
      Rebleeding in types Forrest-IIb occurs also mainly during the first two days.
      Endoscopic hemostasis (electrocoagulation and injection therapy) was performed in
      40 patients. In 6 (15%) cases hemostasis was not achieved. In 8 (20%) cases
      endoscopic hemostasis led to a temporary effect, i.e. rebleeding was seen within
      24-72 hours after endoscopic procedure. Stable hemostasis with endoscopy was
      achieved in 26 (65%) patients.

PMID- 15940175
TI  - [Surgical treatment of complicated ulcers of cardia and sub-cardia].
AB  - Two hundred and two patients with ulcers of a proximal part of the stomach (17.5%
      of all patients with gastric ulcer) were treated. In 135 (64.9%) patients these
      ulcers were complicated: in 28 (20.7%) -- malignant ulcers, in 42 (31.1%) --
      bleeding ulcers, in 53 (39.3%) -- penetrating ones. Surgery was performed in 142
      (70.3%) patients. A high rate of complications dictates a need to reduce period
      of conservative treatment of such ulcers to 6 months -- 1 year. Distal and
      proximal resection of the stomach are main surgeries in elective surgical
      treatment of patients with benign ulcers of cardia and sub-cardia. In malignant
      transformation gastrectomy is the most preferable. Suturing is indicated in
      perforated and bleeding ulcers, and if it is impossible -- distal subtotal
      resection of the stomach.

PMID- 15940176
TI  - [Laparoscopic treatment of peritoneal adhesions].
AB  - Based on experience of treatment of 3000 patients with peritoneal comissures, new
      methods of diagnosis, prevention and treatment of this disease were developed and
      used. Exact verification of location and degree of comissures permits carrying
      out minimally invasive surgical procedures. A new variant of membranous allo
      abdominal graft with anti-infective and anti-adhesive properties was developed
      and used for prevention of comissures. This approach leads to reduction of the
      number of ...

PMID- 15940177
TI  - [One-stage operations on the lungs and other organs in multifocal and metastatic
      cancer].
AB  - Surgical treatment of 135 patients with multifocal and metastatic cancer of the
      lungs and other organs is analyzed. The absence of absolute differential
      diagnostic differences between true poly-neoplasia and synchronous or
      metachronous solitary metastases leads to extension of indications to surgical
      treatment of these patients. Surgical procedures were performed in 109 patients,
      37 (33.9%) of them were one-stage. One-stage procedures meet the requirements of
      radical surgery and are most preferable biologically and clinically. These
      surgeries decrease treatment duration, prolong survival to 3-5 and more years in
      many patients. As cytoreductive operations, one-stage resections improve the
      condition of the patients, enable effective polychemotherapy.

PMID- 15940178
TI  - [Surgical technologies in the treatment of varicose veins of the lower
      extremities complicated with trophic ulcer].
AB  - Results of an open randomized study of staged treatment of 94 patients suffering
      from varicose veins of the lower extremities with open infected trophic ulcers of
      the shank were analyzed. All the patients were divided into 3 groups depending on
      the treatment variant. Based on this study, clinical efficacy of early correction
      of upper vertical venous-venous reflux is substantiated. Efficacy of CO(2) laser
      application for sanation of trophic venous ulcers and practical importance of
      their auto-venous plastic reconstruction are demonstrated. Thus, up-to-date
      technologies provide differential treatment in patients with trophic venous
      ulcers.

PMID- 15940179
TI  - [Surgical treatment of initial forms of varicose veins of the lower extremities].
AB  - Experience in the treatment of 386 patients with stage 2-3 of varicose disease is
      analyzed. There are five main variants of surgical treatment in these patients:
      combined phlebectomy, sclero-obliteration of the trunk, short stripping with
      ligation of insufficient perforant veins, short stripping with excision or
      destruction of varicose branches, short stripping and sclero-obliteration of the
      trunk. It is demonstrated that minimally invasive surgical procedures decrease
      the number of postoperative subcutaneous haematomas, ensure good cosmetic effect,
      allow to avoid an injury of n.saphenus and lymphorrhea. It is concluded that
      minimally invasive surgical procedures may be used for treatment of initial forms
      of varicose disease.

PMID- 15940180
TI  - [Long-term results of reconstructive surgeries in iatrogenic injury of the
      urinary tracts].
AB  - Various reconstructive surgeries were performed in 21 patients because of
      intraoperative injuries of the urinary tracts. In 4 patients trauma of the ureter
      and urinary bladder was associated with obstetric operations (Cesarean section,
      hysterectomy). In 13 cases injury of the ureter was the consequence of
      hysterectomy due to cancer (4), hysteromyoma (4), prolapses of the uterus (1),
      extirpation of the stump of the uterine cervix (1), electrocoagulation of the
      ureter (2) and adnexectomy (1). In 4 patients ligation of the ureter complicated
      surgery for cancer of the sigmoid colon (1) and rectum (1), diverticular disease
      of the colon (1) and portal hepatic cirrhosis with severe ascites. Surgical
      policy was organ-saving. Only in 3 patients with severe acute pyelonephritis
      surgical treatment was performed in two stages with preliminary nephrostomy. In
      the rest cases primary reconstructive surgeries were used. Reconstructive
      surgeries saved the kidney as a functioning organ.

PMID- 15940181
TI  - [Abdomino-anal resection in the treatment of low-ampullar cancer of the rectum].
AB  - Surgical policy was developed for improvement of functional results and quality
      of life in patients operated on for low rectal cancer. This policy includes
      choice of the method of sphincter-saving operation depending on the stage of the
      tumor, grade of malignancy, distance from a low edge of the tumor to dentate
      line. Methods of prevention of ischemia and necrosis of brought down colonic
      transplant and anal incontinence were used. This increased the number of
      sphincter-saving operations in low location of rectal cancer by 35%, reduced the
      rate of necrosis of intestinal transplant from 7 to 4.4%, saved continent
      function and improved significantly quality of life in 89.8% operated patients.

PMID- 15940182
TI  - [Causes and features of involvement of the intestine and its vessels in acute
      disturbance of mesenterial circulation].
AB  - A course of acute disturbance of mesenterial circulation (ADMC) in 346 patients
      (89% of them were over 50 years, mean age 68.4+/-3.6 years) was analyzed.
      Occlusive forms of ADMC occurred in 88% cases (91% of them were due to affection
      of intestinal arterial bed). Atherosclerosis of the aorta or/and it unpaired
      visceral branches was the main cause of ADMC in 96% patients. In 87.6% cases the
      causes of acute mesenterial ischemia were occlusive disease of intestinal vessels
      due to thrombosis and embolism of unpaired visceral branches of the abdominal
      aorta, thrombosis in porto-mesenterial bed. Circulatory disorders on the
      microcirculation level (non-occlusive ischemia) were among the causes in 7.5%
      cases.

PMID- 15940183
TI  - [Possibilities of a compound bone and soft tissue complex in reconstructive
      surgery].
AB  - The method of forming a bone and soft tissue complex for reconstructive surgery
      is presented. Sixty-eight transplantations of compound flaps of soft tissues,
      muscles and bones including ones on microvascular anastomosis were performed in
      66 patients. Good functional and esthetic results were seen in 86.8% cases,
      satisfactory -- in 11.8%. It is very important to form vascular pedicle
      precisely, and to make an adequate choice of the shape and size of the flap.
      There is no prolonged immobilization of the extremity after microsurgical
      transplantation that is very important for children and adolescents because this
      prevents joint stiffness and long stay in bed in conventional treatment (Italian
      plasty, Filatov's graft, etc). The proposed method of forming the bone and soft
      tissue complex simplifies technical aspects of transplantation and monitoring.
      Transplantation of costal-thoracodorsal complex is a method of choice in large
      soft tissue defects.

PMID- 15940184
TI  - [Pattern of excitation in isolated heart of hibernator ground squirrel Citellus
      undulatus].
AB  - Aim of our study was to measure conduction velocity and pattern of excitation
      during hypothermia in hearts of ground squirrels Citellus undulatus, known to be
      most resilient hibernators. We imaged electrical conduction in intact isolated
      hearts of summer active and winter hibernating ground squirrels at temperatures
      varying from +37 degrees C to +3 degrees C. Electrical activity was mapped using
      CCD camera (500 frames/sec) and voltage-sensitive dye di-4-ANEPPS during normal
      sinus rhythm and ventricular pacing. No spontaneous tachyarrhythmia was observed
      in all hearts at any temperature. Hearts were able to maintain spontaneous sinus
      rhythm and normal pattern of epicardial excitation throughout the whole range of
      studied temperatures. Despite responsiveness to pacing in all hearts ventricular
      conduction velocity was significantly reduced (about 10-fold) at low temperatures
      +3 degrees C. Our data provides the first direct demonstration that isolated
      heart of the summer active and winter hibernating ground squirrel Citellus
      undulatus is able to maintain normal excitation pattern in a range of
      temperatures from +37 degrees C to +3 degrees C.

PMID- 15940185
TI  - [Changes of cardiac electrophysiological parameters after destruction of
      epicardial nervous plexi innervating sinoatrial node].
AB  - Electrophysiological methods were used in experiments on 15 dogs for the study of
      topography of right atrial epicardial nerves, their connections with sinoatrial
      node, and possibilities of selective surgical denervation of sinoatrial node.
      Epicardial nerves were electro-coagulated or cryo-destructed in ventral, lateral
      and dorsal atrial zones near base of vena cava inferior. The following parameters
      were registered: heart rate, time of restoration of sinus node function,
      conduction through atrioventricular node, refractoriness of atria and
      atrioventricular node. Comparison of cardiac parameters before and after
      destruction of epicardial nerves showed that in lateral and ventral zones
      sympathetic nerves reach sinus node through lateral and ventral zones while
      parasympathetic -- along dorsal zone. Selective surgical destruction allows to
      modify sinus node function in a desired way.

PMID- 15940187
TI  - [Heart rate turbulence in patients with ventricular tachy arrhythmias of
      noncoronary genesis].
AB  - AIM: To assess parameters of heart rate turbulence in patients with ventricular
      extrasystoles (VES). MATERIAL AND METHODS: Patients with VES during Holter ECG
      monitoring (n=65, age 1-17 years, 32 girls, 33 boys) including 3 with long QT
      syndrome, 4 with catecholaminergic ventricular tachycardia, 1 with arrhythmogenic
      right ventricular dysplasia, 4 with dilated cardiomyopathy, 2 with Brugada
      syndrome, 3 with Duchenne myopathy, and 48 with idiopathic VES. Parameters HRT
      onset and slope were calculated for 1678 VES. During follow-up (6+/-4.9 years)
      deaths, sudden deaths, and such complications as syncope, cardiac dilatation,
      heart failure were registered in 26 patients. RESULTS: HRT slope exceeded 2.5
      ms/RR in all patients. HRT onset was >0 in patients with catecholaminergic
      ventricular tachycardia, dilated cardiomyopathy, and Duchenne myopathy. The
      following complications occurred in 7 of 8 patients (87.5%) with HRT onset >0:
      syncope, sudden deaths (2 patients with dilated cardiomyopathy), dilatation of
      cardiac chambers, tolerance to antiarrhythmic therapy. Patients with long QT
      syndrome and arrhythmogenic right ventricular dysplasia (including 2 who
      afterwards died suddenly) had normal HRT onset. The sensitivity and specificity
      of HRT onset measurement for unfavorable prognosis of VES was 27 and 97%,
      respectively. No relationship was found between HRT slope and onset (r=-0.057).
      CONCLUSION: Pathological HRT (mainly represented by changes of HRT onset) are
      characteristic for organic myocardial diseases. Therefore detection of abnormal
      HRT dictates necessity of exclusion of organic cardiac pathology.

PMID- 15940186
TI  - [The role of mutation in cardiac beta-myosin heavy chain gene in population of
      patients].
AB  - One of most widely spread causes of hypertrophic cardiomyopathy (HCMP) is
      mutation in cardiac beta-myosin heavy chain gene. Data on contribution of this
      mutation to development of HCMP in Russian patients are very limited. We
      conducted screening of beta-myosin heavy chain gene for the presence of mutations
      in 116 patients with confirmed HCMP (probands). DHPLC was used with subsequent
      sequencing of DNA fragments. Genetic defects of beta-myosin heavy chain were
      found more than in every 10-th patient. These defects were represented by 13
      mutations (Ala729Pro mutation was found twice). Phenotypes of majority of known
      mutations in Russian population did not differ substantially from their
      phenotypes in other populations. Six mutations had not been previously described;
      most of them were associated with especially severe clinical and hemodynamic
      signs and relatively unfavorable course of the disease. Thus beta-myosin heavy
      chain gene mutation play important role in etiology of HCMP in patients in
      Russia.

PMID- 15940188
TI  - [Dermatological adverse reactions of amiodarone].
AB  - Amiodarone, an iodine -- rich benzofurane derivate, is a highly effective agent
      for the prophylaxis and treatment of various cardiac arrhythmias, but it is
      associated with numerous side effects. Aim of this study was to elucidate
      dermatological adverse effects of therapy with amiodarone. Patients (n=468, mean
      age 48.7+/-0.7 years) receiving oral amiodarone were followed-up for 1-134 months
      (mean 20.85+/-1.2 months). Photosensitivity was quite common (41.4%). Spectrum of
      skin reactions was wide, ranging from erythema and swelling of area exposed to
      sunshine. Some patients (0.8%) developed pigmentation of the exposed skin areas.

PMID- 15940189
TI  - [Segmental left ventricular function in patients with syndrome X].
AB  - Impulse tissue Doppler study of the left ventricle was carried out in 44 patients
      with cardiac syndrome X (age 47.15+/-6.27 years) and 46 healthy volunteers aged
      35-55 years. Maximal peak velocities "s", "e", "a", "e/a" ratio and segmental
      isovolumic relaxation time "ivrt" were evaluated for each of 18 selected left
      ventricular segments. Criteria of disturbed segmental diastolic left ventricular
      function were e/a ratio <1.0 and ivrt >85 ms. Left ventricular filling was
      abnormal (E/A (min) <1.0) in 18 (40.9%) patients all of whom had segments with
      e/a <1.0. According to e/a values 18 of 26 patients (69,23%) with E/A (min) >1.0
      had segmental dysfunction while 8 patients (30,77%) had intact segmental
      diastolic function. Patients with and without segmental diastolic dysfunction had
      different exercise tolerance, nocturnal blood pressure fall, blood levels of
      glucose and low density lipoprotein cholesterol. Patients with abnormal (IVRT >90
      ms) and normal (IVRT 40-80 ms) left ventricular relaxation had similar numbers of
      dysfunctional segments. Patients with IVRT 80-40 ms and with (n=21) or without
      (n=4) disturbances of segmental relaxation had different age, left ventricular
      myocardial mass index and magnitude of myocardial hypoperfusion.

PMID- 15940190
TI  - [Clinical genetic determinants of carbohydrate metabolism disturbances in
      patients with hypertension and excessive weight].
AB  - AIM: To elucidate associations of polymorphic markers of PPAR, PPARG2, IRS1, IRS2
      genes with disturbances of carbohydrate metabolism in patients with hypertension
      and excessive weight. MATERIAL: Patients (n=145, 53 men and 92 women, age 40-75
      years) with untreated stage 1 hypertension (systolic BP 140-159 and diastolic BP
      <100 mm Hg) and excessive weight or obesity (body mass index >27 kg/m(2)) were
      divided into 2 groups: with (group 1, n=124) and without (group II, n=21)
      disturbances of carbohydrate metabolism. Group I comprised patients with insulin
      resistance, abnormal fasting blood glucose or glucose tolerance, type 2 diabetes.
      Results of oral glucose tolerance test were normal in 25 and abnormal in 99 of
      these patients. RESULTS: Carriers of Pro allele compared with carriers of Ala
      allele of PPARG2 gene had higher frequency of insulin resistance. No association
      was found between insulin resistance and alleles and genotypes of PPAR, IRS1, and
      IRS2 genes. There was an association between diastolic BP and polymorphic markers
      Pro12Ala of PPARG2 gene and C24313G of PPARA gene. Carriers of C allele of PPARA
      gene and Ala allele of PPARG2 gene had higher diastolic BP. No association was
      found between systolic BP and alleles and genotypes of polymorphic markers of
      PPARG2 and PPARA genes.

PMID- 15940191
TI  - [Efficacy and tolerability of two forms of nifedipine in the treatment of
      hypertension].

PMID- 15940192
TI  - [Anomalous origin of left coronary artery from pulmonary trunk: symptoms,
      diagnosis and surgical treatment].
AB  - Anomalous origin of left coronary artery from pulmonary artery is a rare
      congenital pathology causing death of most patients because of various arrhythmia
      and heart failure. The authors present 4 cases of this anomaly with description
      of clinical course, diagnosis and surgical procedures. The first patient was
      operated upon in 12 years after mitral valve replacement. Ligation of anterior
      interventricular and circumflex arteries at their origin in this patient was
      combined with anastomosis between mammary and anterior interventricular coronary
      arteries. Reimplantation of the left coronary artery into the aortic root was
      used in other 3 patients with good immediate postoperative effect. Restoration of
      left ventricular pump function occurred in all 3 patients.

PMID- 15940193
TI  - [Plasma lipids oxidation in patients with occlusive atherosclerosis of lower
      extremities and ischemic heart disease].
AB  - Dynamics of lipoprotein oxidation in blood plasma was studied by Cu-induced
      plasma oxidation in 114 patients with atherosclerosis of lower extremities of
      various severity with and without ischemic heart disease. Preparedness of plasma
      lipoproteins to oxidation in patients was higher than in healthy subjects. Degree
      of oxidizeability increased with increase of severity and extent of
      atherosclerosis and was highest in patients with atherosclerosis of lower
      extremities and ischemic heart disease. There were no significant differences
      between groups of patients with various severity and extent of atherosclerosis in
      levels of total cholesterol and triglycerides as well as in other parameters of
      lipid spectrum. Correlation analysis revealed no relationship between age of
      patients and degree of plasma oxidizeability.

PMID- 15940194
TI  - [Clinical value of allele variants of cytochrome CYP2C9 gene for anticoagulation
      therapy with warfarin].
AB  - Warfarin is metabolized by cytochrome CYP2C9 and its pharmacokinetic properties
      depend on structural polymorphisms of CYP2C9 gene. We studied frequencies of
      allele variants of CYP2C9 gene and associations of individual reaction to
      warfarin intake with genotype of CYP2C9 gene. Population frequencies of CYP2C9x1,
      CYP2C9x2, CYP2C9x3 alleles of CYP2C9 gene in St-Petersburg were 82.66, 11.11, and
      6.32%, respectively. Carriers of CYP2C9x2 and CYP2C9x3 alleles more rapidly
      achieved therapeutic levels of hypocoagulation and required significantly lower
      weekly doses of warfarin.

PMID- 15940195
TI  - [The role of a type of m-choline receptors in realization of vagal influences on
      cardiac rhythm and conduction].

PMID- 15940196
TI  - [Antioxidant properties of statins].
AB  - Statins block expression of protein subunits of Gi-proteins (p22phox and
      gp91phox) which determine oxidase activity of NADPH oxidases and expression of
      GTP-ase (NADPH activator). This leads to suppression of activity of prooxidant
      enzyme systems (NADPH oxidase, xanthine oxidase, oxidase activity of endothelial
      NO-synthase) and diminishment of production of most aggressive free radicals --
      superoxide anion and peroxinitrite. Hyperproduction of these radicals is
      associated with lowering of nitric oxide (NO) level and augmented NO destruction,
      the state of oxidative stress and endothelial dysfunction. Statins increase
      expression of enzymes with antioxidant properties (catalases, paroxonases),
      augment resistance of low density lipoproteins to oxidation, decrease take up of
      oxidized low density lipoproteins by monocytes and differentiation of monocytes
      into macrophages at the account of suppression of cellular scavenger receptor
      CD36 gene expression. Thus statins are powerful antioxidants.

PMID- 15940197
TI  - [Academician Alexander Leonidovitch Myasnikov -- the first Chief Internist of the
      USSR Navy (to the 60-th Anniversary of the Great Victory)].

PMID- 15940203
TI  - [The place of cardiac glycosides in the treatment of chronic heart failure].
AB  - In a series of papers the authors analyze literature data on the use of cardiac
      glycosides for long term treatment of chronic heart failure. Part 1 is devoted to
      clinical pharmacology of glycosides with special emphasis on digoxin. In low
      doses digoxin produces no substantial effect on contractility of left ventricular
      myocardium but can cause worsening of its diastolic function. Favorable action of
      digoxin on clinical course and outcomes of chronic heart failure is most probably
      related to modulation of neuro-humoral systems. Data on factors influencing
      sensitivity to glycosides in various categories of patients with heart failure,
      their interaction with other drugs, and contraindications for digoxin are also
      presented.

PMID- 15940204
TI  - [Is it necessary to detect insulin resistance for diagnosis of metabolic syndrome
      in clinical practice?].
AB  - Metabolic syndrome is widely spread in population especially among subjects with
      risk factors of atherosclerosis related diseases. Since 1988 criteria of
      metabolic syndrome have undergone substantial transformation. Technical
      difficulties related to detection of insulin resistance created obstacles to
      application of the term "metabolic syndrome" in clinical practice. In 2001
      experts of National Cholesterol Education Program in USA suggested new set of
      criteria. The presence of 3 or more of the following 5 components (abdominal
      obesity, hypertriglyceridemia, low level of high density lipoprotein cholesterol,
      hypertension and high fasting blood glucose) allows to diagnose metabolic
      syndrome. These worldwide used criteria do not imply detection of insulin
      resistance. Feasibility of this approach has been confirmed by analysis of
      correlation between presence of markers of insulin resistance and that of
      metabolic syndrome according to novel criteria. This analysis has shown that
      combination of 3 or more components is significantly associated with insulin
      resistance.

PMID- 15940205
TI  - [The place of metoprolol in the treatment of ischemic heart disease].

PMID- 15940206
TI  - Performance and accountability in medical physics: a point of view.

PMID- 15940207
TI  - Virtual micro MLC commissioning.
AB  - The resolution of multileaf collimators (MLCs) is limited by their finite leaf
      width. A commercial package (HD-270) uses 3D couch translation and leaf
      adjustments to emulate smaller leaf widths. In this paper, we report on the
      commissioning of this feature using software testing, dial gauge measurements,
      and film dosimetry. We also identify a variety of limitations: software bugs and
      truncation artifacts, MLC leaf positioning uncertainties (random variations,
      systematic gantry dependence and backlash), and uncertainties in couch
      positioning. These reduce the capabilities of this implementation below that
      achievable theoretically.

PMID- 15940208
TI  - Limited accuracy of dose calculation for large fields at deep depths using the
      BrainSCAN v5.21 treatment planning system.
AB  - The Varian 120 multileaf collimator (MLC) has a leaf thickness of 5 mm projected
      at the isocenter plane and can deliver a radiation beam of large field size (up
      to 30 cm) to be used in intensity-modulated radiotherapy (IMRT). Often the dose
      must be delivered to depths greater than 20 cm. Therefore, during the
      commissioning of the BrainSCAN v5.21 or any radiation treatment-planning (RTP)
      systems, extensive testing of dose and monitor unit calculations must encompass
      the field sizes (1 cm to 30 cm) and the prescription depths (1 cm to 20 cm).
      Accordingly, the central-axis percent depth doses (PDDs) and off-axis percentage
      profiles must be measured at several depths for various field sizes. The data for
      this study were acquired with a 6-MV X-ray beam from a Varian 2100EX LINAC with a
      water phantom at a source-to-surface distance (SSD) of 100 cm. These measurements
      were also used to generate a photon beam module, based on a photon pencil beam
      dose-calculation algorithm with a fast-Fourier transform method. To commission
      the photon beam module used in our BrainSCAN RTP system, we performed a
      quantitative comparison of measured and calculated central-axis depth doses and
      off-axis profiles. Utilizing the principles of dose difference and distance-to
      agreement introduced by Van Dyk et al. [Commissioning and quality assurance of
      treatment planning computers. Int J Radiat Oncol Biol Phys. 1993; 26:261-273],
      agreements between calculated and measured doses are <2% and <2 mm for the
      regions of low- and high-dose gradients, respectively. However, large errors (up
      to approximately 5% and approximately 7% for 20-cm and 30-cm fields,
      respectively, at the depth 20 cm) were observed for monitor unit calculations.
      For a given field size, the disagreement increased with the depth. Similarly, for
      a given depth the disagreement also increase with the field size. These large
      systematic errors were caused by using the tissue maximum ratio (TMR) in
      BrainSCAN v5.21 without considering increased field size as depth increased.
      These errors have been reported to BrainLAB.

PMID- 15940209
TI  - Interfractional anatomic variation in patients treated with respiration-gated
      radiotherapy.
AB  - As quality assurance for respiration-gated treatments using the Varian RPM
      system, we monitor interfractional diaphragm variation throughout treatment using
      extra anterior-posterior (AP) portal images. We measure the superior-inferior (SI
      distance between one or more bony landmarks and the ipsilateral diaphragm dome in
      each such radiograph and calculate its difference, D, from the corresponding
      distance in a planning CT scan digitally reconstructed radiograph (DRR). For each
      patient, the mean of D represents the systematic diaphragm displacement, and the
      standard deviation of D represents random diaphragm variations and is a measure
      of interfractional gating reproducibility. We present results for 31 sequential
      patients (21 lung, 10 liver tumors), each with at least 8 such portal images. For
      all patients, the gate included end-exhale. The patient-specific duty cycle
      ranged from 30% to 60%. All patients received customized audio prompting for
      simulation and treatment, and 14 patients also received visual prompting.
      Respiration-synchronized fluoroscopic movies taken at a conventional simulator
      revealed patient-specific diaphragm excursions from 1.0 cm to 5.0 cm and
      diaphragm excursion within the gate from 0.5 cm to 1.0 cm, demonstrating a
      significant reduction of intra-fractional diaphragm (and by inference tumor)
      motion by respiratory gating. One standard deviation of the systematic
      displacement (the mean of D) was 0.63 cm and 0.48 cm for the lung and liver
      patient groups, respectively. The average +/-1 SD of the random displacements
      (i.e., the average of the standard deviations of D) was 0.42 +/- 0.11 cm and 0.50
      +/- 0.19 for the two groups, respectively. The similar magnitude of the
      systematic and random displacements suggests that both derive from a common
      distribution of interfractional variations. Combining visual with audio prompting
      did not significantly improve performance, as judged by D. Guided by these portal
      images, field changes were made during the course of treatment for 6 patients (1
      lung, 5 liver).

PMID- 15940210
TI  - Maximum MLC opening effect in dynamic delivery of IMRT: leaf-positional analysis.
AB  - The analysis of dynamic multileaf collimator (MLC) positions for the delivered
      intensity-modulated radiotherapy (IMRT) plans is crucial in that it may capture
      dose delivery problems otherwise difficult to observe and quantify in the
      conventional dosimetric measurements with film or with an ionization chamber. In
      some IMRT systems, delivery of IMRT fields starts with a maximum MLC opening
      (roughly the shape of the target in the beam's-eye view) and then proceeds to the
      subsequent dynamic MLC subfields. No irradiation is required in going from the
      initial segment (maximum opening) to the next one, and theoretically, no dose
      should be delivered in that initial moment. However, due to a finite sampling
      time of the MLC controller, the finite speed of the MLC, and a finite leaf
      tolerance, there may be some dose delivered between the first and the second
      segment. The amount of the excess dose is higher for larger dose rates and for a
      smaller number of the total monitor units per IMRT field. The magnitude of the
      dose errors could be in the order of a few percent. Effects similar to the
      maximum MLC opening may occur in other situations as well, for instance, when
      leaves are forced to move over large distances in a short time. Confounding this
      are dose errors due to the uncertainty in the MLC transmission. The analysis of
      the actual leaf positions recorded in the dynamic MLC log file is helpful in
      differentiating between the two types of errors and in determining the optimal
      dynamic MLC delivery parameters.

PMID- 15940211
TI  - Advantages of inflatable multichannel endorectal applicator in the neo-adjuvant
      treatment of patients with locally advanced rectal cancer with HDR brachytherapy.
AB  - High-dose rate endorectal brachytherapy (HDR-EBT) is mainly used as a palliative
      treatment modality. In this paper, we compare dosimetry distributions for a
      single-channel catheter (Miami) applicator with distributions of the inflatable
      multichannel (Novi Sad) endorectal applicator. The comparisons were made with
      respect to dose coverage to the clinical tumor volume as well as to the bladder,
      rectal wall, prostate, and bone marrow. Our results suggest that a multichannel
      applicator provides better sparing of the bone marrow by 50%, clinically
      uninvolved parts of the rectal wall by 70%, and bladder and prostate (in the case
      of male patients) by 100% in terms of ratio of median doses to critical organ
      volume for single- and multichannel endorectal applicators. Our results justify
      the advantage of using a multichannel endorectal brachytherapy applicator as a
      neo-adjuvant treatment of patients with locally advanced rectal cancer.

PMID- 15940212
TI  - A feasibility study of Dynamic Phantom scanner for quality assurance of photon
      beam profiles at various gantry angles.
AB  - The effect of gantry rotation on beam profiles of photon and electron beams is an
      important issue in quality assurance for radiotherapy. To address variations in
      the profiles of photon and electron beams at different gantry angles, a Dynamic
      Phantom scanner composed of a 20 x 12 x 6 cm3 scanning Lucite block was designed
      as a cross-beam-profile scanner. To our knowledge, differences between scanned
      profiles acquired at different gantry angles with a small size Lucite block and
      those acquired a full-size (60 x 60 x 50 cm3) water phantom have not been
      previously investigated. We therefore performed a feasibility study for a first
      prototype Dynamic Phantom scanner without a gantry attachment mount. Radiation
      beams from a Varian LINAC 21EX and 2100C were used. Photon beams (6 MV and 18 MV)
      were shaped by either collimator jaws or a Varian 120 Multileaf (MLC) collimator,
      and electron beams (6 MeV, 12 MeV, and 20 MeV) were shaped by a treatment cone.
      To investigate the effect on profiles by using a Lucite block, a quantitative
      comparison of scanned profiles with the Dynamic Phantom and a full-size water
      phantom was first performed at a 0 degrees gantry angle for both photon and
      electron beams. For photon beam profiles defined by jaws at 1.0 cm and 5.0 cm
      depths of Lucite (i.e., at 1.1 cm and 5.7 cm depth of water), a good agreement
      (less than 1% variation) inside the field edge was observed between profiles
      scanned with the Dynamic Phantom and with a water phantom. The use of Lucite in
      the Dynamic Phantom resulted in reduced penumbra width (about 0.5 mm out of 5 mm
      to 8mm) and reduced (1% to 2%) scatter dose beyond the field edges for both 6 MV
      and 18 MV beams, compared with the water phantom scanner. For profiles of the MLC
      shaped 6 MV photon beam, a similar agreement was observed. For profiles of
      electron beams scanned at 2.9 cm depth of Lucite (i.e., at 3.3 cm depth of
      water), larger disagreements in profiles (3% to 4%) and penumbra width (3 mm to 4
      mm out of 12 mm) were observed. Additional profiles with the gantry at 90 degrees
      and 270 degrees were performed for both MLC- and jaw-shaped photon beams and
      electron beams to evaluate the effect of gantry rotation. General good agreement
      is seen (less than 1 % variation) at all field sizes for collimator-shaped 6 MV
      and 18 MV photon beams. Similar variations observed for MLC-shaped photon beams
      indicate that the uncertainty in MLC position is similar to that for the
      collimator jaws. We conclude that the Dynamic Phantom scanner is a useful device
      for the routine quality assurance on beam profiles of photon beams and for
      constancy check on electron beams at various gantry angles. Caution should be
      taken when using this device to acquire basic electron dosimetry data.

PMID- 15940213
TI  - A dose gradient analysis tool for IMRT QA.
AB  - The use of intensity-modulated radiation therapy (IMRT) has led to an increase in
      the number of complex fields that require measurement and comparison to
      calculated dose distributions in 2D. Current dose-evaluation techniques,
      including isodose line comparisons, displays of the dose difference between
      calculated and measured distributions, and distance-to-agreement (DTA)
      comparisons, are useful for display of differences between two different dose
      distributions but are often of limited value for the assessment of the
      discrepancies in terms of significance and/or cause. In this paper, we present a
      new gradient compensation method for the evaluation of local dosimetric
      differences as a function of the dose gradient at each point in the dose
      distribution. To apply the method, the user specifies a distance parameter
      (typically 1 mm), which is the geometric tolerance the user is prepared to accept
      for the dose comparison. The expected geometric uncertainties in the comparison
      process can include finite calculation and measurement grids, small misalignments
      of measured and calculated results, and volume-averaging effects in the
      measurement detector. Since these uncertainties can obscure the interpretation of
      any of the analysis tools described above, removing dose differences related to
      the tolerable geometric uncertainty helps the gradient compensation method
      highlight algorithm and delivery-related differences. The remaining dose
      differences not explained by the geometric tolerance can then be evaluated
      graphically (dose difference display) or analytically (dose difference dose
      volume histograms)over the entire comparison region.

PMID- 15940217
TI  - Open sesame.

PMID- 15940214
TI  - Validation of physics improvements for IMRT with a commercial treatment-planning
      system.
AB  - A new Pinnacle 3D treatment-planning system software release has recently become
      available (v7.4, Philips Radiation Oncology Systems, Milpitas, CA), which
      supports modeling of rounded multileaf collimator (MLC) leaf ends; it also
      includes a number of other software enhancements intended to improve the overall
      dose calculation accuracy. In this report, we provide a general discussion of the
      dose calculation algorithm and new beam-modeling parameters. The accuracy of a
      diode dosimeter was established for measurement of MLC-shaped beam profiles
      required by the new software version by comparison with film and ion chamber
      measurements in various regions of the field. The results suggest that a suitable
      diode or other small volume dosimeter with appropriate energy sensitivity should
      be used to obtain profiles for commissioning the planning system. Film should be
      used with caution, especially for larger field profile measurements. The dose
      calculation algorithm and modeling parameters chosen were validated through
      various test field measurements including a bar pattern, a strip pattern, and a
      clinical head and neck IMRT field. For the bar and strip patterns, the agreement
      between Pinnacle calculations and diode measurements was generally very good.
      These tests were helpful in establishing the new model parameter values,
      especially tongue-and-groove width, additional interleaf leakage, rounded leaf
      tip radius, and MLC transmission. For the clinical head and neck field, the
      comparison between Pinnacle and film measurements showed regions of approximately
      2 cGy under- or overdose. However, the Pinnacle calculations agreed with diode
      measurements at all points to within 1 cGy or 1% of the maximum dose for the
      field (67 cGy). The greatest discrepancy between film and diode measurements for
      the clinical field (maximum of 2.8%) occurred in low-dose regions in the central
      part of the field. The disagreement may be due to the overresponse of film to
      scattered radiation in the low-dose regions, which have significant shielding by
      the MLCs.

PMID- 15940218
TI  - Acquisition signals shift from US market.

PMID- 15940219
TI  - Beer giant blindsides Ventria's pharmacrop.

PMID- 15940220
TI  - GM rice forges ahead in China amid concerns over illegal planting.

PMID- 15940221
TI  - Dow pulls out of bioplastics due to slow sector maturation.

PMID- 15940223
TI  - Network aims to knit disparate European initiatives.

PMID- 15940222
TI  - Multi-kinase inhibitors create buzz at ASCO.

PMID- 15940226
TI  - Biotech hits regulatory doldrums.

PMID- 15940227
TI  - Better living through microbes.

PMID- 15940228
TI  - National origins of new drugs.

PMID- 15940229
TI  - Cross-border biotech.

PMID- 15940230
TI  - Reexamining the research exemption.

PMID- 15940231
TI  - Keeping your head when all about you are losing theirs.

PMID- 15940232
TI  - Public biotechnology 2004--the numbers.

PMID- 15940233
TI  - The rise of venture capital and biotechnology in the US and Europe.

PMID- 15940234
TI  - Overcoming obviousness when patenting nanotechnology inventions.

PMID- 15940236
TI  - Plasmon coupling measures up.

PMID- 15940237
TI  - Receptor-targeted siRNAs.

PMID- 15940238
TI  - Viral-mediated plant transformation gets a boost.

PMID- 15940239
TI  - "Magic" scissors for genome surgery.

PMID- 15940241
TI  - Functional genome annotation through phylogenomic mapping.
AB  - Accurate determination of functional interactions among proteins at the genome
      level remains a challenge for genomic research. Here we introduce a genome-scale
      approach to functional protein annotation--phylogenomic mapping--that requires
      only sequence data, can be applied equally well to both finished and unfinished
      genomes, and can be extended beyond single genomes to annotate multiple genomes
      simultaneously. We have developed and applied it to more than 200 sequenced
      bacterial genomes. Proteins with similar evolutionary histories were grouped
      together, placed on a three dimensional map and visualized as a topographical
      landscape. The resulting phylogenomic maps display thousands of proteins
      clustered in mountains on the basis of coinheritance, a strong indicator of
      shared function. In addition to systematic computational validation, we have
      experimentally confirmed the ability of phylogenomic maps to predict both mutant
      phenotype and gene function in the delta proteobacterium Myxococcus xanthus.

PMID- 15940245
TI  - Making it in the biotech business.

PMID- 15940242
TI  - Characterization and culture of human embryonic stem cells.
AB  - Human embryonic stem cells have been defined as self-renewing cells that can give
      rise to many types of cells of the body. How and whether these cells can be
      manipulated to replace cells in diseased tissues, used to screen drugs and
      toxins, or studied to better understand normal development, however, depends on
      knowing more about their fundamental properties. Many different human embryonic
      stem cell lines--which are pluripotent, proliferate indefinitely in vitro and
      maintain a normal, euploid karyotype over extended culture--have now been
      derived, but whether these cell lines are in fact equivalent remains unclear. It
      will therefore be important to define robust criteria for the assessment of both
      existing and newly derived cell lines and for the validation of new culture
      conditions.

PMID- 15940247
TI  - Estrogen and progesterone regulate radiation-induced p53 activity in mammary
      epithelium through TGF-beta-dependent pathways.
AB  - DNA damage normally induces p53 activity, but responses to ionizing radiation in
      the mammary epithelium vary among developmental stages. The following studies
      examined the hormones and growth factors that regulate radiation-responsiveness
      of p53 in mouse mammary epithelium. Immunoreactive p21/WAF1 and TUNEL staining
      were used as indicators of p53 activity following exposure to ionizing radiation.
      In ovariectomized mice, radiation-induced accumulation of p21/WAF1 was minimal in
      the mammary epithelial cells (<1%). Systemic injections of estrogen and
      progesterone (E+P) for 72 h were necessary to recover maximal expression of
      p21/WAF1 following ionizing radiation (55%). The effects of E+P on radiation
      induced p21/WAF1 were p53-dependent as responses were absent in Trp53-/- mice.
      Though hormonal treatments stimulated increases in the proportion of cycling
      cells (PCNA-positive), this was not directly correlated with p53 activity. Whole
      organ cultures were used to determine whether E+P act directly upon the mammary
      gland. Treatment with E+P was sufficient to render p53 responsive to radiation,
      but TGF-beta-neutralizing antibodies blocked responsiveness. In the absence of
      E+P, TGF-beta1 alone did not alter p53 activity. These results demonstrate that
      estrogen and progesterone together with TGF-beta signaling are necessary for
      maintenance of p53 activity in the mammary epithelium.

PMID- 15940248
TI  - 7q deletion mapping and expression profiling in uterine fibroids.
AB  - Uterine fibroids are some of the most common tumours of females, but relatively
      little is known about their molecular basis. Several studies have suggested that
      deletions on chromosome 7q could have a role in fibroid formation. We analysed
      165 sporadic uterine fibroids to define a small 3.2 megabase (Mb) commonly
      deleted region on 7q22.3-q31.1, flanked by clones AC005070 and AC007567. We also
      used oligonucleotide microarrays to compare the expression profiles of 10 samples
      of normal myometrium and 15 fibroids, nine of which displayed 7q-deletions.
      Activating transcription factor 3, patched homolog (Drosophila), homeo box A5,
      death-associated protein kinase 1, and retinoic acid receptor responder 3 were
      downregulated, and excision repair crosscomplementing 3, transcription factor AP
      2 gamma and protein kinase C beta 1 were upregulated in fibroids. New pathways
      were discovered related to fibroid formation. The presence or absence of 7q
      deletions did not dramatically affect the global expression pattern of the
      tumours; changes, however, were observed in genes related to vesicular transport
      and nucleic acid binding.

PMID- 15940249
TI  - Gamma secretase inhibitor blocks Notch activation and induces apoptosis in
      Kaposi's sarcoma tumor cells.
AB  - Kaposi's sarcoma (KS) is a common neoplasm in HIV-1-infected individuals causing
      significant morbidity and mortality. Despite recent advances, the pathogenesis of
      this potentially life-threatening neoplasm remains unclear, and there is
      currently no cure for KS. Notch proteins are known to play a fundamental role in
      cell fate decisions including proliferation, differentiation, and apoptosis. It
      is, therefore, not surprising that Notch proteins have been implicated in
      tumorigenesis and appear to function as either oncogenes or tumor suppressor
      proteins depending on cellular context. In this report, we demonstrate elevated
      levels of activated Notch-1, -2, and -4 in KS tumor cells in vivo and in vitro
      compared to endothelial cells, the precursor of the KS cell. Notch activation was
      confirmed through luciferase reporter assays and localization of Hes
      (Hairy/Enhancer of Split)-1 and Hey (Hairy/Enhancer of Split related with YRPW)1
      (primary targets of the Notch pathway) in KS cell nuclei. Studies using gamma
      secretase inhibitors (GSI and LY-411,575), which block Notch activation, resulted
      in apoptosis in primary and immortalized KS cells. Similar studies injecting GSI
      into established KS cell tumors on mice demonstrated growth inhibition or tumor
      regression that was characterized by apoptosis in treated, but not control
      tumors. The results indicate that KS cells overexpress activated Notch and
      interruption of Notch signaling inhibits KS cell growth. Thus, targeting Notch
      signaling may be of therapeutic value in KS patients.

PMID- 15940250
TI  - Accelerated proliferation of myeloma cells by interleukin-6 cooperating with
      fibroblast growth factor receptor 3-mediated signals.
AB  - Interleukin-6 (IL-6) is a cytokine that regulates the proliferation of some tumor
      cells including multiple myeloma (MM). Ectopic expression of fibroblast growth
      factor receptor 3 (FGFR 3) associated with the chromosomal translocation,
      t(4;14)(p16.3;q32), is frequently found in MM, and therefore, has been implicated
      in the neoplastic transformation of this disease. Here, we show that IL-6
      together with FGF enhanced proliferation of a myeloma cell line, KMS-11 carrying
      t(4;14)(p16.3;q32) and the FGFR 3-transfected U 266 myeloma cell line which
      ectopically expressed FGFR 3 but responded to neither IL-6 nor FGF alone. In KMS
      11, IL-6 activated signal transducer and activator of transcription 3 (STAT 3)
      while FGF activated extracellular signal-regulated kinase 1/2 (ERK 1/2) and
      phosphatidylinositol (PI)-3 kinase. As both MEK inhibitors and a PI 3-kinase
      inhibitor abolished the effect of IL-6 and FGF, the activation of both the ERK
      1/2 and PI 3-kinase signaling cascades is essential for the proliferation of KMS
      11 enhanced by IL-6 and FGF. Furthermore, the FGF-induced activation of ERK 1/2
      contributed to the serine phosphorylation of STAT 3, suggesting that the
      signaling crosstalk between the cytokine receptor, IL-6 receptor alpha/gp 130 and
      the growth factor receptor tyrosine kinase, FGFR 3. These results indicate that
      FGFR 3 plays a crucial role in the accelerated proliferation of MM carrying
      t(4;14)(p16.3;q32).

PMID- 15940251
TI  - Nfkb 1 is dispensable for Myc-induced lymphomagenesis.
AB  - Rel/NF-kappaB transcription factors are critical arbiters of immune responses,
      cell survival, and transformation, and are frequently deregulated in cancer. The
      p50 NF-kappaB 1 component of Rel/NF-kappaB DNA-binding dimers regulates genes
      involved in both cell cycle traverse and apoptosis. Nfkb 1 loss accelerates B
      cell growth and leads to increased B cell turnover in vivo, phenotypes akin to
      those manifested in B cells of Emu-Myc transgenic mice, a model of human Burkitt
      lymphoma. Interestingly, Emu-Myc B cells express reduced levels of cytoplasmic
      and nuclear NF-kappaB 1 and have reduced Rel/NF-kappaB DNA-binding activity,
      suggesting that Myc-mediated repression of NF-kappaB 1 might mediate its
      proliferative and apoptotic effects on B cells. Furthermore, Nfkb 1 expression
      was reduced in the majority of Emu-Myc lymphomas and was also suppressed in human
      Burkitt lymphoma. Nonetheless, loss of Nfkb 1 did not appreciably affect Myc's
      proliferative or apoptotic responses in B cells and had no effect on lymphoma
      development in Emu-Myc mice. Therefore, Nfkb 1 is dispensable for Myc-induced
      lymphomagenesis..

PMID- 15940252
TI  - RAI(ShcC/N-Shc)-dependent recruitment of GAB 1 to RET oncoproteins potentiates PI
      3-K signalling in thyroid tumors.
AB  - RAI, also named ShcC/N-Shc, one of the members of the Shc proteins family, is a
      substrate of the RET receptor tyrosine kinase. Here, we show that RAI forms a
      protein complex with both RET/MEN 2 A and RET/PTC oncoproteins. By co
      immunoprecipitation, we found that RAI associates with the Grb 2-associated
      binder 1 (GAB 1) adapter. This association is constitutive, but, in the presence
      of RET oncoproteins, both RAI and GAB 1 are tyrosine-phosphorylated, and the
      stoichiometry of this interaction remarkably increases. Consequently, the p 85
      regulatory subunit of phosphatidylinositol-3 kinase (PI-3 K) is recruited to the
      complex, and its downstream effector Akt is activated. We show that human thyroid
      cancer cell lines derived from papillary or medullary thyroid carcinoma (PTC or
      MTC) carrying, respectively, RET/PTC and RET/MEN 2 A oncoproteins express RAI
      proteins. We also show that human PTC samples express higher levels of RAI, when
      compared to normal thyroid tissue. In thyroid cells expressing RET/PTC 1, ectopic
      expression of RAI protects cells from apoptosis; on the other hand, the silencing
      of endogenous RAI by small inhibitory duplex RNAs in a PTC cell line that
      expresses endogenous RET/PTC 1, increases the rate of spontaneous apoptosis.
      These data suggest that RAI is a critical substrate for RET oncoproteins in
      thyroid carcinomas.

PMID- 15940253
TI  - Expression of the candidate tumor suppressor gene hSRBC is frequently lost in
      primary lung cancers with and without DNA methylation.
AB  - Recently, the human SRBC (hSRBC) gene, a candidate tumor suppressor gene (TSG),
      has been mapped to the chromosomal region 11p 15.5--p15.4 where frequent allele
      loss has been described in lung cancer. Aberrant methylation (referred to as
      methylation) of the promoter region of TSGs has been identified as an important
      mechanism for gene silencing. Loss of hSRBC protein expression occurs frequently
      in lung cancer cell lines and sodium bisulfite sequencing of the promoter region
      of hSRBC in several lung cancer cell lines suggested that methylation plays an
      important role in inactivating hSRBC. To determine the methylation status of
      hSRBC in a large collection of primary lung cancer samples, corresponding
      nonmalignant lung tissues and lung cancer cell lines (N=52), we designed primers
      for a methylation-specific PCR assay. Methylation was detected in 41% of primary
      non-small-cell lung cancers (NSCLC) (N=107) and in 80% of primary small-cell lung
      cancers (SCLC) (N=5), but was seen only in 4% of corresponding nonmalignant lung
      tissues (N=103). In all, 79% of lung cancer cell lines were methylated and the
      frequency of hSRBC methylation was significantly higher in SCLC (100%) than in
      NSCLC (58%) cell lines. Normal hSRBC protein expression was detected in only 18%
      of primary NSCLCs (N=93) by immunostaining and a significant association between
      loss of protein expression and methylation was found. hSRBC re-expression was
      observed after treatment of lung cancer cells with the demethylating agent 5-aza
      2'-deoxycytidine. In addition, 45% of the 76 hSRBC immunostaining-negative NSCLCs
      did not have hSRBC promoter methylation, indicating that other mechanisms of
      hSRBC expression silencing also exist. Both hSRBC immunostaining and methylation
      results did not correlate with clinicopathological characteristics of these
      patients. Our findings suggest that hSRBC is a candidate TSG involved in lung
      cancer pathogenesis, where expression is frequently inactivated by methylation
      and other mechanisms.

PMID- 15940254
TI  - Gene expression profiles in cells transformed by overexpression of the IGF-I
      receptor.
AB  - To identify genes associated with insulin-like growth factor-I receptor (IGF-IR)
      mediated cellular transformation, we isolated genes that are differentially
      expressed in R- cells (derived from the IGF-IR knockout mouse) and R+ cells (R-
      cells that overexpress the IGF-IR). From these, 45 genes of known function were
      expressed at higher levels in R+ cells and 22 were expressed at higher levels in
      R- cells. Differential expression was confirmed by Northern blot analysis of R+
      and R- cells. Genes expressed more abundantly in R+ cells are associated with (1)
      tumour growth and metastasis including, betaigH3, mts1, igfbp5 protease, and
      mystique; (2) cell division, including cyclin A1 and cdk1; (3) signal
      transduction, including pkcdeltabp and lmw-ptp; and (4) metabolism including
      ATPase H+ transporter and ferritin. In MCF-7 cells IGF-I induced expression of
      two genes, lasp-1 and mystique, which could contribute to metastasis. Lasp-1
      expression required activity of the PI3-kinase signalling pathway. Mystique was
      highly expressed in metastatic but not in androgen-dependent prostate cancer cell
      lines and Mystique overexpression in MCF-7 cells promoted cell migration and
      invasion. We conclude that genes identified in this screen may mediate IGF-IR
      function in cancer progression.

PMID- 15940255
TI  - The 'regulatory' beta-subunit of protein kinase CK2 negatively influences p53
      mediated allosteric effects on Chk2 activation.
AB  - The 'regulatory' beta-subunit of protein kinase CK2 has previously been shown to
      interact with protein kinases such as A-Raf, c-Mos, Lyn and Chk1 in addition to
      the catalytic subunit of CK2. Sequence alignments suggest that these interactions
      have a structural basis, and hence other protein kinases harboring corresponding
      sequences may be potential interaction partners for CK2beta. We show here that
      Chk2 specifically interacts with CK2beta in vitro and in cultured cells, and that
      activation of Chk2 leads to a reduction of this interaction. Additionally, we
      show that the presence of the CK2beta-subunit significantly reduces the Chk2
      catalysed phosphorylation of p53 in vitro. These findings support the notion that
      CK2beta can act as a general modulator of remote docking sites in protein kinase-
      substrate interactions.

PMID- 15940256
TI  - Ets-1 expression promotes epithelial cell transformation by inducing migration,
      invasion and anchorage-independent growth.
AB  - Ets-1 is the prototype of the family of ETS transcription factors. In human
      tumors, Ets-1 is expressed in endothelial cells and fibroblasts of the tumor
      stroma and is proposed to play a role in tumor vascularization and invasion by
      upregulating expression of matrix-degrading proteases. In human carcinomas, Ets-1
      is also expressed by neoplastic cells, but little is known about the functional
      implications of this observation. We have addressed the role of Ets-1 in
      epithelial HeLa tumor cells by selecting stably Ets-1 over and underexpressing
      HeLa cells. Ets-1 expression increases the transformed phenotype of HeLa cells,
      by promoting cell migration, invasion and anchorage-independent growth, while Ets
      1 downregulation reduces cell attachment. In correlation with these results, Ets
      1 upregulation increases integrinbeta2 expression but not that of other
      integrins. These results suggest that, in addition to its role in the tumor
      stroma, Ets-1 may also promote tumor development and progression by increasing
      neoplastic transformation.

PMID- 15940257
TI  - Lipid modification of GRN163, an N3'-->P5' thio-phosphoramidate oligonucleotide,
      enhances the potency of telomerase inhibition.
AB  - The vast majority of human cancers express telomerase activity, while most human
      somatic cells do not have detectable telomerase activity. Since telomerase plays
      a critical role in cell immortality, it is an attractive target for a selective
      cancer therapy. Oligonucleotides complementary to the RNA template region of
      human telomerase (hTR) have been shown to be effective inhibitors of telomerase
      and, subsequently, cancer cell growth in vitro. We show here that a lipid
      modified N3'-->P5' thio-phosphoramidate oligonucleotide (GRN163L) inhibits
      telomerase more potently than its parental nonconjugated thio-phosphoramidate
      sequence (GRN163). Cells were treated with both the first- (GRN163) and second
      generation (GRN163L) oligonucleotides, including a mismatch control, with or
      without a transfection enhancer reagent. GRN163L inhibited telomerase activity
      effectively in a dose-dependent manner, even without the use of a transfection
      reagent. The IC50 values for GRN163 in various cell lines were on average
      sevenfold higher than for GRN163L. GRN163L inhibition of telomerase activity
      resulted in a more rapid loss of telomeres and cell growth than GRN163. This
      report is the first to show that lipid modification enhanced the potency of the
      novel GRN163 telomerase inhibitor. These results suggest that the lipid
      conjugated thio-phosphoramidates could be important for improved pharmacodynamics
      of telomerase inhibitors in cancer therapy.

PMID- 15940258
TI  - Diallyl trisulfide-induced G(2)-M phase cell cycle arrest in human prostate
      cancer cells is caused by reactive oxygen species-dependent destruction and
      hyperphosphorylation of Cdc 25 C.
AB  - Molecular mechanism of cell cycle arrest caused by diallyl trisulfide (DATS), a
      garlic-derived cancer chemopreventive agent, has been investigated using PC-3 and
      DU 145 human prostate cancer cells as a model. Treatment of PC-3 and DU 145
      cells, but not a normal prostate epithelial cell line (PrEC), with growth
      suppressive concentrations of DATS caused enrichment of the G(2)-M fraction. The
      DATS-induced cell cycle arrest in PC-3 cells was associated with increased
      Tyr(15) phosphorylation of cyclin-dependent kinase 1 (Cdk 1) and inhibition of
      Cdk 1/cyclinB 1 kinase activity. The DATS-treated PC-3 and DU 145 cells also
      exhibited a decrease in the protein level of Cdc 25 C and an increase in its
      Ser(216) phosphorylation. The DATS-mediated decrease in protein level and
      Ser(216) phosphorylation of Cdc 25 C as well as G(2)-M phase cell cycle arrest
      were significantly attenuated in the presence of N-acetylcysteine implicating
      reactive oxygen species (ROS) in cell cycle arrest caused by DATS. ROS generation
      was observed in DATS-treated PC-3 and DU 145 cells. DATS treatment also caused an
      increase in the protein level of Cdk inhibitor p21, but DATS-induced G(2)-M phase
      arrest was not affected by antisense-mediated suppression of p21 protein level.
      In conclusion, the results of the present study indicate that DATS-induced G(2)-M
      phase cell cycle arrest in human prostate cancer cells is caused by ROS-mediated
      destruction and hyperphosphorylation of Cdc 25 C.

PMID- 15940259
TI  - A p53-dominant transcriptional response to cisplatin in testicular germ cell
      tumor-derived human embryonal carcinoma.
AB  - Testicular germ cell cancers remain one of the few solid tumors routinely cured
      in advanced stages with conventional cisplatin-based chemotherapy. The mechanisms
      remain largely unknown. Through use of gene-expression array profiling we define
      immediate transcriptional targets in response to cisplatin in testicular germ
      cell-derived human embryonal carcinoma cells. We report 46 genes upregulated and
      five genes repressed by cisplatin. Several of these gene products, including FAS,
      TRAILR3, PHLDA3, LRDD, and IER3 are previously implicated in the apoptotic death
      receptor pathway, while others including SESN1, FDXR, PLK3, and DDIT4 are known
      mediators of reactive oxygen species generation. Approximately 54% of the
      upregulated genes are established or suspected downstream targets of p53.
      Specific siRNA to p53 prevents cisplatin-mediated activation of p53 and p53
      pathway genes and renders embryonal carcinoma cells relatively resistant to
      cisplatin cytotoxicity. Interestingly, in p53 knockdown cells nearly the entire
      set of identified cisplatin targets fail to respond or have a diminished response
      to cisplatin, suggesting that many are new direct or indirect targets of p53
      including GPR87, STK17A, INPP5D, FLJ11259, and EPS8L2. The data indicate that
      robust transcriptional activation of p53 is linked to the known hypersensitivity
      of testicular germ cell tumors to chemotherapy. Many of the gene products may
      participate in the unique curability of this disease.

PMID- 15940260
TI  - Proteomics analysis of H-RAS-mediated oncogenic transformation in a genetically
      defined human ovarian cancer model.
AB  - RAS is a small GTP binding protein mutated in approximately 30% human cancer.
      Despite its important role in the initiation and progression of human cancer, the
      underlying mechanism of RAS-induced human epithelial transformation remains
      elusive. In this study, we probe the cellular and molecular mechanisms of RAS
      mediated transformation, by profiling two human ovarian epithelial cell lines.
      One cell line was immortalized with SV40 T/t antigens and the human catalytic
      subunit of telomerase (T29), while the second cell line was transformed with an
      additional oncogenic ras(V12) allele (T29H). In total, 32 proteins associated
      with RAS-mediated transformation have been identified using peptide mass
      fingerprinting. These protein targets are involved in several cellular pathways,
      including metabolism, redox balance, calcium signaling, apoptosis, and cellular
      methylation. One such target, the 40 kDa procaspase 4 is significantly
      upregulated at the protein level in RAS-transformed T29H cells, related directly
      to signaling through MEK, but not PI3 kinase. Cellular caspase 4 activity is,
      however, suppressed in the T29H cells, suggesting that the maturation process of
      caspase 4 is abrogated in RAS-transformed T29H cells. Consistent with this
      notion, transformed T29H cells were less susceptible to the toxic effects of anti
      Fas antibody than were immortalized, nontransformed T29 cells, associated with
      less activation of caspase 4. This study demonstrates that functional proteomic
      analysis of a genetically defined cancer model provides a powerful approach
      toward systematically identifying cellular targets associated with oncogenic
      transformation.

PMID- 15940261
TI  - AID binds to transcription-induced structures in c-MYC that map to regions
      associated with translocation and hypermutation.
AB  - Translocation and aberrant hypermutation of c-MYC are common in B-cell lymphomas.
      Activation-induced Cytidine Deaminase (AID) initiates switch recombination and
      somatic hypermutation in B cells by targeted deamination of transcribed genes. We
      show that transcription of the immunoglobulin S regions and c-MYC results in
      formation of similar DNA structures, 'G-loops', which contain a cotranscriptional
      RNA: DNA hybrid on the C-rich strand and single-stranded regions and G4 DNA on
      the G-rich strand. AID binds specifically to G-loops within transcribed S regions
      and c-MYC, and G-loops in c-MYC map to the regions associated with translocation
      breakpoints and aberrant hypermutation in B-cell lymphomas. Aberrant targeting of
      AID to DNA structures formed upon c-MYC transcription may therefore contribute to
      the genetic instability of c-MYC in B-cell malignancies.

PMID- 15940262
TI  - Annexin A6 stimulates the membrane recruitment of p120GAP to modulate Ras and Raf
      1 activity.
AB  - Annexin A6 is a calcium-dependent membrane-binding protein that interacts with
      signalling proteins, including the GTPase-activating protein p120GAP, one of the
      most important inactivators of Ras. Since we have demonstrated that annexin A6
      inhibits EGF- and TPA-induced Ras signalling, we investigated whether modulation
      of Ras activity by annexin A6 was mediated via altered subcellular localization
      of p120GAP. First, we exploited our observation that high-density lipoproteins
      (HDL) can activate the Ras/MAP kinase pathway. Expression of annexin A6 caused a
      significant reduction in HDL-induced activation of Ras and Raf-1. Annexin A6
      promoted membrane binding of p120GAP in vitro, and plasma membrane targeting of
      p120GAP in living cells, both in a Ca(2+)-dependent manner, which is consistent
      with annexin A6 promoting the Ca(2+)-dependent assembly of p120GAP-Ras at the
      plasma membrane. We then extended these studies to other cell types and stimuli.
      Expression of annexin A6 in A431 cells reduced, while RNAi-mediated suppression
      of annexin A6 in HeLa cells enhanced EGF-induced Ras and Erk activation.
      Importantly, the enhancement of Ras activation following RNAi-mediated reduction
      in p120GAP levels was more marked in annexin A6-expressing A431 cells than
      controls, indicating that the effect of annexin A6 on Ras was mediated via
      p120GAP. Finally, we demonstrated that annexin A6 promotes plasma membrane
      targeting of p120GAP in A431 cells in response to a variety of stimuli, resulting
      in colocalization with H-Ras. These findings demonstrate an important role for
      annexin A6 in regulating plasma membrane localization of p120GAP and hence Ras
      activity.

PMID- 15940263
TI  - Novel inosine monophosphate dehydrogenase inhibitor VX-944 induces apoptosis in
      multiple myeloma cells primarily via caspase-independent AIF/Endo G pathway.
AB  - Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme required
      for the de novo synthesis of guanine nucleotides from IMP. VX-944 (Vertex
      Pharmaceuticals, Cambridge, MA, USA) is a small-molecule, selective,
      noncompetitive inhibitor directed against human IMPDH. In this report, we show
      that VX-944 inhibits in vitro growth of human multiple myeloma (MM) cell lines
      via induction of apoptosis. Interleukin-6, insulin-like growth factor-1, or co
      culture with bone marrow stromal cells (BMSCs) do not protect against VX-944
      induced MM cell growth inhibition. VX-944 induced apoptosis in MM cell lines with
      only modest activation of caspases 3, 8, and 9. Furthermore, the pan-caspase
      inhibitor z-VAD-fmk did not inhibit VX-944-induced apoptosis and cell death.
      During VX-944-induced apoptosis, expressions of Bax and Bak were enhanced, and
      both apoptosis-inducing factor (AIF) and endonuclease G (Endo G) were released
      from the mitochondria to cytosol, suggesting that VX-944 triggers apoptosis in MM
      cells primarily via a caspase-independent, Bax/AIF/Endo G pathway. Importantly,
      VX-944 augments the cytotoxicity of doxorubicin and melphalan even in the
      presence of BMSCs. Taken together, our data demonstrate a primarily non-caspase
      dependent apoptotic pathway triggered by VX-944, thereby providing a rationale to
      enhance MM cell cytotoxicity by combining this agent with conventional agents
      which trigger caspase activation.

PMID- 15940264
TI  - The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a
      novel functional interaction between estrogen receptor alpha and transcriptional
      elongation factor cyclin T1.
AB  - Estrogen receptor alpha (ERalpha) regulates transcription of specific genes and
      is believed to play a major role in breast tumorigenesis. We previously
      identified estrogen down regulated gene 1 (EDG1 (also known as HEXIM1)) using the
      C-terminus of ERalpha (E/F domain) as bait in yeast two-hybrid screenings. Here
      we report on the role of EDG1 as a coregulator of ERalpha transcriptional
      activity. We observe an interaction between EDG1 and ERalpha. EDG1 inhibits the
      transcriptional activity of ERalpha and this is dependent upon the C-terminus of
      EDG1. The C-terminus of EDG1/HEXIM1 was recently shown to inhibit the positive
      transcription elongation factor b (P-TEFb) by interacting with the cyclin T1
      subunit. Here we show that ERalpha interacts with cyclin T1, cyclin T1 and ER co
      occupancy on the promoter region of an ER target gene, and that this interaction
      plays an important role in ERalpha-induced gene expression. The interaction of
      ERalpha with cyclin T1 also allows ERalpha to compete with EDG1 for cyclin T1,
      and may release cyclin T1 from EDG1 repression. Conversely, increased EDG1
      expression results in inhibition of cyclin T1 recruitment and ERalpha DNA
      binding. Our results support a novel functional interaction between ERalpha and
      cyclin T1 that is modulated by EDG1.

PMID- 15940265
TI  - Enhanced radiation damage of tumor vasculature by mTOR inhibitors.
AB  - It is known that radiation activates the phosphoinositol-3 kinase (PI3K)/Akt
      pathway and that inhibition of PI3K or Akt sensitizes tumor vasculature to
      radiotherapy. Mammalian target of rapamycin (mTOR) is a downstream target of Akt,
      and we hypothesized that irradiation activates mTOR signaling in both glioma and
      endothelial cells (ECs) and that radiosensitization results from inhibiting mTOR
      signaling. mTOR inhibitors, rapamycin and RAD001 (everolimus) were found to
      radiosensitize vascular ECs, but failed to sensitize glioma cells as determined
      by clonogenic assay. Therefore, we investigated the anti-angiogenic effects of
      mTOR inhibitors. Increased phospho-mTOR protein was detected in irradiated human
      umbilical vein endothelial cells (HUVEC), but not in GL261 glioma cells. Phospho
      S6, a biomarker for mTOR signaling, was also found to be induced following
      irradiation in HUVEC and this effect was inhibited by PI3K or mTOR inhibitors.
      Significant increase in cleaved caspase 3 was detected when Rad001 was combined
      with radiation. Endothelial tube formation was significantly diminished following
      treatment with rapamycin and 3 Gy of radiation. Histological sections of GL261
      tumors from mice showed a greatly reduced vascular density when treated with
      RAD001 and radiation. Power Weighted Doppler of glioma xenografts in mice showed
      a significant reduction in vasculature and blood flow compared with mice treated
      with 3 Gy or RAD001 alone. We conclude that irradiation activates mTOR signaling
      in vascular endothelium and that rapamycin and RAD001 increased apoptosis of ECs
      in response to radiation. To the authors' best knowledge this is the first study
      which demonstrates that mTOR inhibitors may be a way to target the vasculature by
      radiosensitizing the vascular endothelium resulting in better tumor control as
      seen in experiments demonstrating increased tumor growth delay in mice treated
      with rapamycin with radiation compared with mice treat with either treatment
      alone. We conclude that mTOR inhibitors have increased efficacy as
      antiangiogenics when combined with radiation.

PMID- 15940266
TI  - Stabilization of PML nuclear localization by conjugation and oligomerization of
      SUMO-3.
AB  - The PML gene of acute promyelocytic leukemia (APL) encodes a cell-growth and
      tumor suppressor. PML localizes to discrete nuclear bodies (NBs) that are
      disrupted in APL cells, resulting from a reciprocal chromosome translocation t
      (15;17). Here we show that the nuclear localization of PML is also regulated by
      SUMO-3, one of the three recently identified SUMO isoforms in human cells. SUMO-3
      bears similar subcellular distribution to those of SUMO-1 and -2 in the
      interphase nuclear body, which is colocalized with PML protein. However, both
      SUMO-2 and -3 are also localized to nucleoli, a region lacking SUMO-1.
      Immunoprecipitated PML protein bears SUMO-3 moiety in a covalently modified form,
      supporting the notion that PML is conjugated by SUMO-3. To determine the
      functional relevance of SUMO-3 conjugation on PML molecular dynamics, we
      suppressed SUMO-3 protein expression using a siRNA-mediated approach. Depletion
      of SUMO-3 markedly reduced the number of PML-containing NBa and their integrity,
      which is rescued by exogenous expression of SUMO-3 but not SUMO-1 or SUMO-2. The
      specific requirement of SUMO-3 for PML nuclear localization is validated by
      expression of SUMO-3 conjugation defective mutant. Moreover, we demonstrate that
      oligomerization of SUMO-3 is required for PML retention in the nucleus. Taken
      together, our studies provide first line of evidence showing that SUMO-3 is
      essential for PML localization and offer novel insight into the pathobiochemistry
      of APL.

PMID- 15940267
TI  - The 2,5 oligoadenylate synthetase/RNaseL pathway is a novel effector of BRCA1-
      and interferon-gamma-mediated apoptosis.
AB  - BRCA1 has been reported to have roles in DNA damage repair, cell cycle checkpoint
      control, transcriptional regulation and ubiquitination. We have previously
      demonstrated that BRCA1 is a potent activator of a subset of interferon (IFN)
      regulated genes and that BRCA1 synergistically activated a number of these genes
      in the presence of IFN-gamma, but not type I IFNs. Here we report that one of
      these targets, 2,5 oligoadenylate synthetase (2,5 OAS), is a mediator of
      BRCA1/IFN-gamma-induced apoptosis. We show that the induction of 2,5 OAS in
      response to IFN-gamma is BRCA1 and STAT1 dependent. Consistent with a role as a
      negative regulator of proliferation, transient transfection of 2,5 OAS into
      breast cancer cell lines results in decreased colony growth and apoptosis.
      Furthermore we show that IFN-gamma-induced apoptosis is dependent on functional
      BRCA1 and STAT1 and we demonstrate that IFN-gamma-induced apoptosis is dependent
      on 2,5 OAS induction. 2,5 OAS is the only known upstream regulator of RNaseL, a
      recently identified hereditary prostate tumour suppressor gene implicated in
      apoptosis. We propose that BRCA1 may be an upstream regulator of RNaseL, acting
      in concert with IFN-gamma to transcriptionally activate 2,5 OAS, leading to the
      downstream activation of RNaseL and apoptosis.

PMID- 15940268
TI  - Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-x(L)
      reduction thereby enhancing UV-light induced apoptosis.
AB  - Ultraviolet (UV) light exposure is a common cause of epithelial-derived skin
      cancers, and the epidermal response to UV-light has been extensively studied
      using both mouse models and cultured human keratinocytes (KCs). Elimination of
      cells with UV-induced DNA damage via apoptosis provides a powerful mechanism to
      minimize retention or expansion of genetically abnormal cells. This cell editing
      function has largely been ascribed to the biological role of the p53 tumor
      suppressor gene, as mutations or deletions involving p53 have been linked to skin
      cancer development. Rather than introducing mutations, or using cells with
      complete loss of wild-type p53, we used an siRNA-based approach to knockdown, but
      not eliminate, p53 levels in primary cultures of human KCs followed by UV
      irradiation. Surprisingly, when p53 levels were reduced by 50-80% the apoptosis
      induced by exposure to UV-light was accelerated and markedly enhanced (two- to
      three- fold) compared to control siRNA treated KCs. The p53 siRNA treated KCs
      were characterized by elevated E2F-1 levels accompanied by accelerated
      elimination of the Mcl-1 and Bcl-x(L) antiapoptotic proteins, as well as enhanced
      Bax oligomerization. Forced overexpression of either Mcl-1 or Bcl-x(L) reduced
      the UV-light enhanced apoptotic response in p53 siRNA treated KCs. We conclude
      that p53 not only can provide proapoptotic signals but also regulates a survival
      pathway influencing Mcl-1 and Bcl-x(L) levels. This overlooked survival function
      of p53 may explain previous paradoxical responses noted by investigators using
      p53 heterozygous and knockout mouse models, and opens up the possibility that not
      all liaisons within the cell involving p53 necessarily represent fatal
      attractions.

PMID- 15940269
TI  - A complex pattern of mutations and abnormal splicing of Smad4 is present in
      thyroid tumours.
AB  - Sensitivity to transforming growth factor-beta is impaired in thyroid tumours.
      Similar to Mad -- Mother Against Decapentaplegic-(Smad)4 is frequently altered in
      cancers, but its involvement in this system is unknown. We analysed 56 thyroid
      tumours of various histotypes for Smad4 mutations by PCR-SSCP and sequencing,
      linking them to Smad4 reactivity as examined by immunohistochemistry (IHC), and
      29 of them also for abnormalities in RNA expression due to alternative splicing.
      In all, 15/56 cases (27%), both benign and malignant lesions, harbour alterations
      of Smad4 coding sequence. We found several novel intragenic mutations (13
      missense, two silent, one frameshift and one large insertion-deletion), with high
      incidence in the linker region. A subset of mutated tumours failed to express
      Smad4 protein by IHC. We have also detected four alternatively spliced tumour
      associated Smad4 isoforms, lacking portions of the linker region, and three more
      due to unreported internal exon-exon rearrangements. Smad4 is both frequently
      mutated and deregulated by aberrant splicing in thyroid tumours and these
      alterations may contribute as an early event to thyroid tumorigenesis.

PMID- 15940270
TI  - Discrimination between serous low malignant potential and invasive epithelial
      ovarian tumors using molecular profiling.
AB  - Tumors of low malignant potential (LMP) represent 20% of epithelial ovarian
      cancers (EOCs) and are associated with a better prognosis than the invasive
      tumors (TOV). Defining the relationship between LMPs and TOVs remains an
      important goal towards understanding the molecular pathways that contribute to
      prognosis, as well as providing molecular markers, for these EOCs. To this end,
      DNA microarray analyses were performed either in a primary culture or a tumor
      tissue model system and selected candidate genes showing a distinctive expression
      profile between LMPs and TOVs were identified using a class prediction approach
      based on three statistical methods of analysis. Both model systems appear
      relevant as candidate genes identified by either model allowed the proper
      reclassification of samples as either LMPs or TOVs. Selected candidate genes
      (CAS, CCNE1, LGALS8, ITGbeta3, ATP1B1, FLIP, KRT7 and KRT19) were validated by
      real-time quantitative PCR analysis and show differential expression between LMPs
      and TOVs. Immunohistochemistry analyses showed that the two tumor classes were
      distinguishable by their expression of CAS, TNFR1A, FLIP, CKS1 and CCNE1. These
      results define signature patterns for gene expression of LMPs and TOVs and
      identify gene candidates that warrant further study to deepen our understanding
      of the biology of EOC.

PMID- 15940271
TI  - Intron polymorphism (EPIC-PCR) reveals phylogeographic structure of Zacco
      platypus in China: a possible target for aquaculture development.
AB  - The present study aims at a phylogeographic description of Zacco platypus from
      southeast China, in order to detect subdivisions within the nominal species. Two
      main basins were sampled: the Chang Jiang (Yangstze River) in central and east
      China (Hunan and Sichuan provinces) and the Xi Jiang, the more southern main
      tributary of the Zhu Jiang (Pearl River, Guangxi province). A total of 27 intron
      systems were tested, five of them were informative and gave 12 interpretable and
      polymorphic loci. Within the diversity of Z. platypus, four genetic groups were
      identified by multidimensional (FCA) analyses, corresponding to distinct genetic
      pools. The geographical distribution of the genetic groups corresponds neither
      with the drainage structure, nor the geographic distances between samples. It
      follows that isolation by distance and limited migration are insufficient to
      explain this geographic structure. The history of the river network therefore
      appears to have played an important role.

PMID- 15940272
TI  - A comparison of regression interval mapping and multiple interval mapping for
      linked QTL.
AB  - Regression interval mapping and multiple interval mapping are compared with
      regard to mapping linked quantitative trait loci (QTL) in inbred-line cross
      experiments. For that purpose, a simulation study was performed using genetic
      models with two linked QTL. Data were simulated for F(2) populations of different
      sizes and with all QTL and marker alleles fixed for alternative alleles in the
      parental lines. The criteria for comparison are power of QTL identification and
      the accuracy of the QTL position and effect estimates. Further, the estimates of
      the relative QTL variance are assessed. There are distinct differences in the QTL
      position estimates between the two methods. Multiple interval mapping tends to be
      more powerful as compared to regression interval mapping. Multiple interval
      mapping further leads to more accurate QTL position and QTL effect estimates. The
      superiority increased with wider marker intervals and larger population sizes. If
      QTL are in repulsion, the differences between the two methods are very
      pronounced. For both methods, the reduction of the marker interval size from 10
      to 5 cM increases power and greatly improves QTL parameter estimates. This
      contrasts with findings in the literature for single QTL scenarios, where a
      marker density of 10 cM is generally considered as sufficient. The use of
      standard (asymptotic) statistical theory for the computation of the standard
      errors of the QTL position and effect estimates proves to give much too
      optimistic standard errors for regression interval mapping as well as for
      multiple interval mapping.

PMID- 15940273
TI  - Comparing Bayesian estimates of genetic differentiation of molecular markers and
      quantitative traits: an application to Pinus sylvestris.
AB  - Comparison of the level of differentiation at neutral molecular markers
      (estimated as F(ST) or G(ST)) with the level of differentiation at quantitative
      traits (estimated as Q(ST)) has become a standard tool for inferring that there
      is differential selection between populations. We estimated Q(ST) of timing of
      bud set from a latitudinal cline of Pinus sylvestris with a Bayesian hierarchical
      variance component method utilizing the information on the pre-estimated
      population structure from neutral molecular markers. Unfortunately, the between
      family variances differed substantially between populations that resulted in a
      bimodal posterior of Q(ST) that could not be compared in any sensible way with
      the unimodal posterior of the microsatellite F(ST). In order to avoid publishing
      studies with flawed Q(ST) estimates, we recommend that future studies should
      present heritability estimates for each trait and population. Moreover, to detect
      variance heterogeneity in frequentist methods (ANOVA and REML), it is of
      essential importance to check also that the residuals are normally distributed
      and do not follow any systematically deviating trends.

PMID- 15940274
TI  - Does insecticide resistance alone account for the low genetic variability of
      asexually reproducing populations of the peach-potato aphid Myzus persicae?
AB  - The typical life cycle of aphids includes several parthenogenetic generations and
      a single sexual generation (cyclical parthenogenesis), but some species or
      populations are totally asexual (obligate parthenogenesis). Genetic variability
      is generally low in these asexually reproducing populations, that is, few
      genotypes are spread over large geographic areas. Both genetic drift and natural
      selection are often invoked to account for this low genetic variability. The
      peach-potato aphid, Myzus persicae, which encompasses both cyclical and obligate
      parthenogens, has developed several insecticide resistance mechanisms as a
      consequence of intense insecticide use since the 1950s. We collected asexually
      reproducing M. persicae from oilseed rape and examined genetic variability at
      eight microsatellite loci and three insecticide resistance genes to determine
      whether their genetic structure was driven by drift and/or selection. We
      identified only 16 multilocus microsatellite genotypes among 255 individuals. One
      clone, which combined two insecticide resistance mechanisms, was frequently
      detected in all populations whatever their location over a large geographical
      area (the northern half of France). These unexpected findings suggest that drift
      is not the unique cause of this low variability. Instead, the intensification of
      both insecticide treatments and oilseed rape cultivation may have favored a few
      genotypes. Thus, we propose that selective pressures resulting from human
      activities have considerably modified the genetic structure of M. persicae
      populations in northern France in a relatively short period of time.

PMID- 15940275
TI  - Measuring the genetic structure of the pollen pool as the probability of paternal
      identity.
AB  - Contemporary pollen flow in forest plant species is measured by the probability
      of paternal identity (PPI) for two randomly sampled offspring, drawn from a
      single female, and contrasting that with PPI for two random offspring, drawn from
      different females. Two different estimation strategies have emerged: (a) an
      indirect approach, using the 'genetic structure' of the pollen received by
      different mothers and (b) a direct approach, based on parentage analysis. The
      indirect strategy is somewhat limited by the assumptions, but is widely useful.
      The direct approach is most appropriate where a large majority of the true
      fathers can be identified exactly, which is sometimes possible with high
      resolution SSR markers. Using the parentage approach, we develop estimates of
      PPI, showing that the obvious estimates are severely biased, and providing an
      unbiased alternative. We then illustrate the methods with SSR data from a 36-tree
      isolated population of Pinus sylvestris from the Meseta region of Spain, for
      which categorical paternity assignment was available for over 95% of offspring.
      For all the females combined, we estimate that PPI=0.0425, indicating uneven male
      reproductive contributions. Different (but overlapping) arrays of males pollinate
      different females, and for the average female, PPI=0.317, indicating substantial
      'pollen structure' for the population. We also relate the direct measures of PPI
      to those available from indirect approaches, and show that they are generally
      comparable.

PMID- 15940276
TI  - Hybrid zones between invasive Rorippa austriaca and native R. sylvestris
      (Brassicaceae) in Germany: ploidy levels and patterns of fitness in the field.
AB  - Hybrid zones may serve as natural laboratories for evolutionary studies. One
      common viewpoint is that hybrids may always be less fit than their parents due to
      genetic discontinuities. An alternative idea is that genotype-environment
      interactions influence the outcome of natural hybridization. Our comparative
      study of two different natural hybrid zones between the invasive diploid Rorippa
      austriaca and the native polyploid R. sylvestris in Germany identified the ploidy
      level as a major determinant of hybrid fitness. Different ploidy levels and
      patterns of fitness were detected in different hybrid zones. In one hybrid zone
      (Mulheim, Ruhr valley) hybrids were pentaploid and showed a relatively high seed
      set, whereas in the second hybrid zone (Randersacker, Main valley) hybrids were
      triploid and displayed extremely low fitness values. Analyses of fitness values
      in different natural hybrid zones between the same two species may lead to very
      different conclusions about the evolutionary significance of natural
      hybridization.

PMID- 15940277
TI  - Biotech, the environment and the three Ps.

PMID- 15940278
TI  - One hundred years of hormones.

PMID- 15940279
TI  - Phytoremediation.

PMID- 15940280
TI  - New superbug or tempest in a teapot?

PMID- 15940282
TI  - Adopting an orphan.

PMID- 15940281
TI  - Common defences.

PMID- 15940284
TI  - Keeping your lawn wet.

PMID- 15940285
TI  - The effects of histone deacetylase inhibitors on heterochromatin: implications
      for anticancer therapy?
AB  - Histone acetylation regulates many chromosome functions, such as gene expression
      and chromosome segregation. Histone deacetylase inhibitors (HDACIs) induce growth
      arrest, differentiation and apoptosis of cancer cells ex vivo, as well as in vivo
      in tumour-bearing animal models, and are now undergoing clinical trials as anti
      tumour agents. However, little attention has been paid to how HDACIs function in
      these biological settings and why different cells respond in different ways.
      Here, we discuss the consequences of inhibiting histone deacetylases in cycling
      versus non-cycling cells, in light of the dynamics of histone acetylation
      patterns with a specific emphasis on heterochromatic regions of the genome.

PMID- 15940286
TI  - Degenerate mitochondria.
AB  - Mitochondria are the main sites of biological energy generation in eukaryotes.
      These organelles are remnants of a bacterial endosymbiont that took up residence
      inside a host cell over 1,500 million years ago. Comparative genomics studies
      suggest that the mitochondrion is monophyletic in origin. Thus, the original
      mitochondrial endosymbiont has evolved independently in anaerobic and aerobic
      environments that are inhabited by diverse eukaryotic lineages. This process has
      resulted in a collection of morphologically, genetically and functionally
      heterogeneous organelle variants that include anaerobic and aerobic mitochondria,
      hydrogenosomes and mitosomes. Current studies aim to determine whether a central
      common function drives the retention of mitochondrial organelles in different
      eukaryotic organisms.

PMID- 15940287
TI  - Case study: management of advanced prostate cancer with soft tissue metastases.

PMID- 15940288
TI  - Case study: management of lymph node-positive disease detected at radical
      prostatectomy.

PMID- 15940289
TI  - Association of CYP2A6*1B genetic variant with the amount of smoking in French
      adults from the Stanislas cohort.
AB  - This study was designed in order to investigate the influence of the genetic
      polymorphism of CYP2A6 on the amount of smoking. In all, 463 French adults
      included in the Stanislas cohort were studied and underwent two examinations at 5
      years distance (t0 and t(+5) years). Information on their smoking habits was
      collected. They were genotyped by RFLP for the CYP2A6*1A, CYP2A6*1B and CYP2A6*4
      alleles. CYP2A6*1B and CYP2A6*4 allele frequencies were 32 and 4%, respectively.
      The subjects carrying the CYP2A6*1B allele oxidize nicotine to cotinine faster
      than subjects with the CYP2A6*1A allele. The number of cigarettes smoked per day
      was significantly higher in the CYP2A6*1B/*1B group as compared to the
      CYP2A6*1A/*1A group (P = 0.01 at t0; P = 0.001 t(+5) years), with a larger
      increase in their daily cigarettes consumption over the 5-year period (P =
      0.006). No significant difference in the smoking status was observed according to
      the CYP2A6 genotype. These data suggest that the CYP2A6*1B is associated with the
      number of cigarettes smoked per day.

PMID- 15940290
TI  - Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD.
AB  - Genetic and pharmacological studies have emphasised the role of serotonin 5
      hydroxytryptamine (5-HT) as a possible etiologic factor in the development of
      attention-deficit hyperactivity disorder (ADHD). Tryptophan hydroxylase (TPH) is
      a rate-limiting enzyme in the biosynthesis of serotonin from tryptophan.
      Originally, the TPH gene was thought to be widely expressed, but a second form of
      TPH, TPH2, was recently identified and the TPH2 gene was found to be solely
      expressed in the brain. We examined eight single nucleotide polymorphisms (SNP)
      in the TPH2 gene for association with ADHD in 179 Irish nuclear families.
      Transmission disequilibrium test analysis revealed significant association
      between the T allele of marker rs1843809 with the disorder (chi2=12.2, P=0.0006,
      OR=2.36). Stratifying data by the sex of the transmitting parent showed that this
      association was enhanced when paternal transmission was considered (OR=3.7). In
      addition, several haplotypes (all including the associated marker) were
      associated with ADHD. These preliminary findings suggest that TPH2 is a
      susceptibility locus for ADHD. Further confirmation, preferably from different
      ethnic groups, is required to firmly implicate TPH2 in the pathophysiology of
      ADHD.

PMID- 15940291
TI  - Estrogen receptor alpha gene polymorphisms and anxiety disorder in an elderly
      population.

PMID- 15940292
TI  - Association of the paternally transmitted copy of common Valine allele of the
      Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene with
      susceptibility to ADHD.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable,
      neurodevelopmental disorder with onset in early childhood. Genes involved in
      neuronal development and growth are, thus, important etiological candidates and
      brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in
      the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is
      involved in the survival and differentiation of dopaminergic neurons in the
      developing brain (of relevance because drugs that block the dopamine transporter
      can be effective therapeutically). The common Val66Met functional polymorphism in
      the human BDNF gene (rs 6265) was genotyped in a collaborative family-based
      sample of 341 white UK or Irish ADHD probands and their parents. We found
      evidence for preferential transmission of the valine (G) allele of BDNF (odds
      ratio, OR=1.6, P=0.02) with a strong paternal effect (paternal transmissions:
      OR=3.2, P=0.0005; maternal transmissions: OR=1.00; P=1.00). Our findings support
      the hypothesis that BDNF is involved in the pathogenesis of ADHD. The
      transmission difference between parents raises the possibility that an epigenetic
      process may be involved.

PMID- 15940293
TI  - Genetic tests of biologic systems in affective disorders.
AB  - To liberate candidate gene analyses from criticisms of inexhaustiveness of
      examination of specific candidate genes, or incompleteness in the choice of
      candidate genes to study for specific neurobiological pathways, study of sizeable
      sets of genes pertinent to each putative pathophysiological pathway is required.
      For many years, genes have been tested in a 'one by one' manner for association
      with major affective disorders, primarily bipolar illness. However, it is
      conceivable that not individual genes but abnormalities in several genes within a
      system or in several neuronal, neural, or hormonal systems are implicated in the
      functional hypotheses for etiology of affective disorders. Compilation of
      candidate genes for entire pathways is a challenge, but can reasonably be carried
      out for the major affective disorders as discussed here. We present here five
      groupings of genes implicated by neuropharmacological and other evidence, which
      suggest 252 candidate genes worth examining. Inexhaustiveness of gene
      interrogation would apply to many studies in which only one polymorphism per gene
      is analyzed. In contrast to whole-genome association studies, a study of a
      limited number of candidate genes can readily exploit information on genomic
      sequence variations obtained from databases and/or resequencing, and has an
      advantage of not having the complication of an extremely stringent statistical
      criterion for association.

PMID- 15940294
TI  - Behavioral deficits associated with fetal alcohol exposure are reversed by
      prenatal thyroid hormone treatment: a role for maternal thyroid hormone
      deficiency in FAE.
AB  - Children prenatally exposed to alcohol typically exhibit behavioral
      abnormalities, including hyperactivity, learning deficits, and an increased
      prevalence of depression. Similar impairments are found in children of
      hypothyroid mothers, and we have shown that alcohol-consuming rat dams have
      suppressed hypothalamic-pituitary-thyroid (HPT) function. Therefore, we
      hypothesized that suppressed maternal thyroid hormonal milieu may contribute to
      the deleterious consequences of prenatal alcohol exposure. We aimed first to
      confirm and then to reverse the behavioral deficits in the fetal alcohol exposed
      (FAE) rat offspring by administration of thyroxine (T4) to the alcohol-consuming
      dams. Adult offspring prenatally exposed to ethanol (FAE; 35% ethanol-derived
      calories), pair-fed (PF) or control (C) diets were tested in the Morris water
      maze (MWM), the forced swim test (FST), and the open field test (OFT) to assess
      spatial learning, depressive behavior, and exploratory behavior/anxiety,
      respectively. Adult FAE offspring took longer to locate a hidden platform in the
      MWM and showed increased depressive behavior in the FST both of which were
      reversed by administration of T4 to the alcohol-consuming mother. We found sex
      and brain region-specific alterations in expression of genes involved in these
      behaviors in FAE adult offspring. Specifically, decreased hippocampal GAP-43 mRNA
      levels in adult FAE females and decreased glucocorticoid receptor (GR) expression
      in the amygdala of male and female FAE offspring were observed. The decreased
      mRNA levels of GAP-43 and GR were normalized by T4 treatment to the alcohol
      consuming mother. Our results suggest that the suppressed HPT function of the
      alcohol-consuming mother contributes to the behavioral and cognitive dysfunctions
      observed in the offspring.

PMID- 15940295
TI  - Evidence for linkage on 21q and 7q in a subset of autism characterized by
      developmental regression.
AB  - Autism is a pervasive developmental disorder with a strong genetic component.
      While candidate regions of the genome have been identified, location of genes
      conferring susceptibility to autism has been hindered by the heterogeneity within
      this clinically defined disorder, and the likely contribution of many genes of
      weak effect. Subsetting samples on the basis of distinct, nondiagnostic clinical
      features has been recommended to decrease sample heterogeneity. In this study,
      linkage analysis was performed on a subset of families in the database of the
      Autism Genetic Resource Exchange (AGRE). This set of autism-affected relative
      pairs (n=34) was also concordant for a history of developmental regression as
      measured by the Autism Diagnostic Interview-Revised (ADI-R). In this sample, a
      maximum multipoint LOD score of 3.4 under the dominant mode of inheritance and an
      NPL score of 3.0 (P=1.3 x 10(-3)) were observed on chromosome 21 near D21S1437.
      On chromosome 7 near D7S483 a LOD score of 2.0 under the dominant mode of
      inheritance and an NPL score of 3.7 (P=7.9 x 10(-5)) were observed. Genetic
      elements in these regions of 21q and 7q are likely to confer susceptibility to
      autism or modify the disease presentation in a subgroup of children characterized
      by a history of developmental regression.

PMID- 15940296
TI  - Meta-analysis reveals association between serotonin transporter gene STin2 VNTR
      polymorphism and schizophrenia.
AB  - The serotonin transporter gene (SLC6A4) is a candidate gene for schizophrenia
      based on serotonin transporter's crucial role in serotonergic neurotransmission.
      However, association studies have produced conflicting results regarding the
      association between two common SLC6A4 gene polymorphisms, the promoter
      insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR) polymorphisms,
      and schizophrenia susceptibility. To further elucidate the putative association
      between the two SLC6A4 gene polymorphisms and schizophrenia susceptibility, we
      performed a meta-analysis based on all original published association studies
      between schizophrenia and the 5-HTTLPR and STin2 VNTR polymorphisms published
      before April 2004. Our analyses showed no statistically significant evidence for
      the association between the Short allele of the 5-HTTLPR polymorphism and
      schizophrenia (random-effects pooled odds ratio (OR)=0.99, 95% Confidence
      Interval (CI)=0.92-1.07, Z=-0.23, P=0.82) from 19 population-based association
      studies consisting of 2990 case and 3875 control subjects. However, highly
      significant evidence for association between the STin2.12 allele of the STin2
      VNTR polymorphism (random-effects pooled OR=1.24, 95% CI=1.11-1.38, Z=3.82,
      P=0.00014) and schizophrenia was found from 12 population-based association
      studies consisting of 2177 cases and 2369 control subjects. Our meta-analysis
      suggests that the STin2.12 allele of the STin2 VNTR polymorphism is likely a risk
      factor for schizophrenia susceptibility. Our data imply that following completion
      of the International HapMap Project, a comprehensive evaluation of a set of
      markers that fully characterize the linkage disequilibrium relationships at the
      SLC6A4 gene should be tested in large well-characterized clinical samples in
      order to understand the role of this gene in schizophrenia susceptibility.

PMID- 15940297
TI  - Identification of a potential bipolar risk haplotype in the gene encoding the
      winged-helix transcription factor RFX4.
AB  - The gene encoding the transcription factor RFX4 represents an excellent
      neurobiological and positional candidate gene for Bipolar disorder due to the
      potential involvement of RFX4 proteins in the regulation of circadian rhythms and
      the proximity of the locus to numerous linkage signals on chromosome 12q23. In
      this study we have sought to identify common variants within the gene, which
      might confer risk to the disease in our large UK Caucasian sample of Bipolar
      patients (676 DSMIV Bipolar I probands, 690 controls). RFX4 was screened for
      sequence variants and the LD block structure across the genomic region determined
      using 22 biallelic polymorphisms (minor allele frequency >or=0.1). Through
      analysis of 10 haplotype-tagging markers and using a two-stage approach (subset
      I: 347 cases, 374 controls; subset II: 329 cases, 316 controls), we identified a
      haplotype at rs10778502 and ss24735177, which showed nominally significant
      disease association in our full sample (haplotype-specific P=0.002, global
      P=0.017; subset I: haplotype-specific P=0.0002, global P=0.0008; subset II:
      haplotype-specific P=0.572, global P=0.109). Evidence for potential disease
      association with mutations across the RFX4 region came also from the analysis of
      the nearby microsatellite D12S2072 (empirical P=0.009 in our full sample).
      Investigation of RFX4 brain cDNA tagged by rs10778502 provided evidence for
      significant allelic differences in expression (P<0.001), where some of the
      variance was accounted for by the genotype at ss24735177. Our findings thus
      indicate the potential functional relevance of the associated haplotype and now
      require replication in independent samples.

PMID- 15940298
TI  - siRNA-mediated knockdown of the serotonin transporter in the adult mouse brain.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressant
      drugs that increase the extracellular levels of serotonin by blocking the
      reuptake activity of the serotonin transporter (SERT). Although SSRIs elevate
      brain serotonergic neurotransmission acutely, their full therapeutic effects
      involve neurochemical adaptations that emerge following chronic drug
      administration. The adaptive downregulation of SERT has recently been implicated
      in the therapeutic response of SSRIs. Interestingly, studies using SERT-knockout
      mice reveal somewhat paradoxical depression-related effects, probably specific to
      the downregulation of SERT during early development. However, the behavioral
      significance of SSRI-mediated downregulation of SERT during adulthood is still
      unknown. We investigated whether somatic gene manipulation, triggered by infusing
      short interfering RNA (siRNA) into the ventricular system, would enable the
      downregulation of SERT in the adult mouse brain. Infusing the SERT-targeting
      siRNA, for 2 weeks, significantly reduced the mRNA levels of SERT in raphe
      nuclei. Further, a significant, specific and widespread downregulation of SERT
      binding sites was achieved in the brain. In contrast, 2-week infusion of the
      SSRI, citalopram, produced a widespread downregulation of SERT-binding sites,
      independent of any alterations at the mRNA level. Irrespective of their
      mechanisms for downregulating SERT in the brain, infusions of SERT-siRNA or
      citalopram elicited a similar antidepressant-related behavioral response in the
      forced swim test. These results signify a role for the downregulation of SERT in
      mediating the antidepressant action of SSRIs in adults. Further, these data
      demonstrate that siRNA-induced widespread knockdown of gene expression serves as
      a powerful tool for assessing the function of endogenous genes in the adult
      brain.

PMID- 15940299
TI  - Brain-derived neurotrophic factor variants are associated with childhood-onset
      mood disorder: confirmation in a Hungarian sample.
AB  - Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has been
      implicated in the neurobiology of depression. Our group has previously reported
      an association between a BDNF variant and childhood-onset mood disorder (COMD) in
      an adult sample from Pittsburgh. We hypothesize that variants at the BDNF locus
      are associated with COMD. Six BDNF polymorphisms were genotyped in 258 trios
      having juvenile probands with childhood-onset DSM-IV major depressive or
      dysthymic disorder. BDNF markers included the (GT)n microsatellite, Val66Met and
      four other single-nucleotide polymorphisms (SNPs) distributed across the BDNF
      gene. Family-based association and evolutionary haplotype analysis methods were
      used. Analysis of linkage disequilibrium (LD) revealed substantial LD among all
      six polymorphisms. Analyses of the Val66Met polymorphism demonstrated significant
      overtransmission of the val allele (chi2=7.12, d.f.=1, P=0.0076). Consistent with
      the pattern of LD, all other SNPs showed significant biased transmission. The
      (GT)n microsatellite alleles also indicated a trend towards biased transmission
      (170 bp: Z=2.095, P=0.036). Significant haplotypes involved Val66Met and BDNF2
      (P=0.0029). In this Hungarian sample, we found all five BDNF SNPs tested and a
      haplotype containing the BDNF Val66Met Val allele to be associated with COMD.
      These results provide evidence that BDNF variants affect liability to juvenile
      onset mood disorders, supported by data from two independent samples.

PMID- 15940300
TI  - Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair
      genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21,
      10p14-p12 and 18q22.
AB  - Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex
      genetic aetiology. We have undertaken a genome-wide scan in one of the largest
      samples of bipolar affected sibling pairs (ASPs) using a two-stage approach
      combining sample splitting and marker grid tightening. In this second stage
      analysis, we have examined 17 regions that achieved a nominally significant
      maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X
      chromosome) in stage one. The second stage has added 135 ASP families to bring
      the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have
      been used to screen the human genome at a density of 10 cM in the first stage
      sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model,
      two markers gave LOD scores exceeding 3 with two-point analysis: D4S392
      (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive
      evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS=2.61) and
      4q12-q21 (MLS=2.38). 6q16-q21 is of particular interest because our data,
      together with those from two recent genome scans, make this the best supported
      linkage region in BPAD. Further, our data show evidence of a gender effect at
      this locus with increased sharing predominantly within the male-male pairs. Our
      scan also provides support for linkage (MLS> or =1.5) at several other regions
      that have been implicated in meta-analyses of bipolar disorder and/or
      schizophrenia including 9p21, 10p14-p12 and 18q22.

PMID- 15940301
TI  - Serotonin transporter polymorphism and potential response to SSRIs in bulimia
      nervosa.

PMID- 15940302
TI  - Relationship of a 5-HT transporter functional polymorphism to 5-HT1A receptor
      binding in healthy women.

PMID- 15940303
TI  - Direct targeting of hippocampal neurons for apoptosis by glucocorticoids is
      reversible by mineralocorticoid receptor activation.
AB  - An important question arising from previous observations in vivo is whether
      glucocorticoids can directly influence neuronal survival in the hippocampus. To
      this end, a primary postnatal hippocampal culture system containing mature
      neurons and expressing both glucocorticoid (GR) and mineralocorticoid (MR)
      receptors was developed. Results show that the GR agonist dexamethasone (DEX)
      targets neurons (microtubule-associated protein 2-positive cells) for death
      through apoptosis. GR-mediated cell death was counteracted by the MR agonist
      aldosterone (ALDO). Antagonism of MR with spironolactone ([7alpha-(acetylthio)-3
      oxo-17alpha-pregn-4-ene-21 carbolactone] (SPIRO)) causes a dose-dependent
      increase in neuronal apoptosis in the absence of DEX, indicating that nanomolar
      levels of corticosterone present in the culture medium, which are sufficient to
      activate MR, can mask the apoptotic response to DEX. Indeed, both SPIRO and
      another MR antagonist, oxprenoate potassium ((7alpha,17alpha)-17-hydroxy-3-oxo-7
      propylpregn-4-ene-21-carboxylic acid, potassium salt (RU28318)), accentuated DEX
      induced apoptosis. These results demonstrate that GRs can act directly to induce
      hippocampal neuronal death and that demonstration of their full apoptotic potency
      depends on abolition of survival-promoting actions mediated by MR.

PMID- 15940304
TI  - Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients
      with schizophrenia.
AB  - Patients with schizophrenia have reduced neurotrophin levels in their
      dorsolateral prefrontal cortex (DLPFC) compared to normal unaffected individuals.
      The tyrosine kinase-containing receptors, trkB and trkC, mediate the growth
      promoting effects of neurotrophins and respond to changes in growth factor
      availability. We hypothesized that trkB and/or trkC expression would be altered
      in the DLPFC of patients with schizophrenia. We measured mRNA encoding the
      tyrosine kinase domain (TK+)-containing form of trkB and measured pan trkC mRNA
      in schizophrenics (N=14) and controls (N=15) using in situ hybridization. TrkB
      and trkC mRNAs were detected in large and small neurons in multiple cortical
      layers of the human DLPFC. We found significantly diminished expression of
      trkB(TK+) mRNA in large neurons in multiple cortical layers of patients as
      compared to controls, while small neurons also showed reductions in trkB(TK+)
      mRNA that did not reach statistical significance. In normals, strong positive
      correlations were found between trkB(TK+) mRNA levels and brain-derived
      neurotrophic factor (BDNF) mRNA levels among various neurons, while no
      correlation between BDNF and trkB(TK+) was found in patients with schizophrenia.
      TrkC mRNA was also reduced in the DLPFC of schizophrenics in large neurons in
      layers II, III, V and VI and in small neurons in layer IV. Since neurons in the
      DLPFC integrate and communicate signals to various cortical and subcortical
      regions, these reductions in growth factor receptors may compromise the function
      and plasticity of the DLPFC in schizophrenia.

PMID- 15940305
TI  - A frameshift mutation in Disrupted in Schizophrenia 1 in an American family with
      schizophrenia and schizoaffective disorder.
AB  - In a large Scottish pedigree, a balanced translocation t(1;11)(q42.1;q14.3)
      segregates with major mental illness, including schizophrenia, bipolar disorder,
      and recurrent major depression. The translocation is predicted to result in the
      loss of the C-terminal region of the protein product of Disrupted In
      SChizophrenia 1 (DISC1), a gene located on 1q42.1. Since this initial discovery,
      DISC1 has been functionally implicated in several processes, including
      neurodevelopment. Based on the genetic and functional evidence that DISC1 may be
      associated with schizophrenia, we sequenced portions of DISC1 in 28 unrelated
      probands with schizophrenia and six unrelated probands with schizoaffective
      disorder, ascertained as part of a large sibpair study. We detected a 4 bp
      deletion at the extreme 3' end of exon 12 in a proband with schizophrenia. The
      mutation was also present in a sib with schizophrenia, a sib with schizoaffective
      disorder, and the unaffected father, while the mutation was not detected in 424
      control individuals. The mutation is predicted to cause a frameshift and encode a
      truncated protein with nine abnormal C-terminal amino acids. The truncated
      transcript is detectable, but at a reduced level, in lymphoblastoid cell lines
      from three of four mutation carriers. These findings are consistent with the
      possibility that mutations in the DISC1 gene can increase the risk for
      schizophrenia and related disorders.

PMID- 15940306
TI  - Dopamine transporter haplotype and attention-deficit hyperactivity disorder.

PMID- 15940307
TI  - [Medical truths].

PMID- 15940308
TI  - [Drugs for adults--and for the children?].

PMID- 15940309
TI  - [Progress and high-cost medicine].

PMID- 15940310
TI  - [Simulation of waiting time and effectiveness in hospitals].
AB  - BACKGROUND: Many Norwegian hospitals have to cancel elective surgery because of
      acute cases, and ring fencing of elective surgery is a frequently discussed
      measure. In this article we discuss advantages and disadvantages of ring fencing
      in relation to the results from a simulation model. MATERIAL AND METHODS: Model
      simulations were done in the computer program Powersim Constructor 2.5. RESULTS:
      We found that combined acute and elective departments are expected to have
      shorter waiting time and less use of overtime compared with separate acute and
      elective departments, as more flexible use of capacity results in higher average
      capacity utilization. In a combined department, elective patients run the risk of
      having their operation cancelled, but they may expect a shorter waiting time
      before treatment. INTERPRETATION: Our results indicate that ring fencing in
      itself is not beneficial, as total capacity utilization declines. On the other
      hand, separate departments may facilitate an increase in efficiency in the
      elective surgery department; this may shorten waiting time.

PMID- 15940311
TI  - [Reversible infertility from nonsteroidal anti-inflammatory drugs].
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective
      cyclooxygenase-2 inhibitors may interfere with ovulation and the rupture of the
      follicle, causing reversible infertility. METHOD: Literature review. RESULTS:
      Reversible infertility is shown both in animal and human studies of these drugs.
      As determined by ultrasound, the drugs may delay or inhibit ovulation. These
      findings are also confirmed by a few randomized controlled studies showing an
      increase in time from the luteinizing hormone surge to rupture of the follicle
      and an increased size of the unruptured follicle. Most of the hormone analyses
      show values in accordance with the ovulation/menstrual cycle. Also, two
      epidemiological studies have shown an association between NSAID use and
      spontaneous abortion. These studies have methodological weaknesses and their
      findings have to be elucidated in future studies. INTERPRETATION: Women with
      fertility problems should avoid not only the selective cyclooxygenase-2
      inhibitors, but also the traditional NSAIDs. However, women with rheumatic
      disease responding well to therapy should consult their physicians before
      stopping treatment. Reduced dose of a NSAID and temporary stop of drug treatment
      early in the menstrual cycle, or alternative drug treatment, may be a solution.
      NSAIDs should not be used in the last eight weeks of pregnancy.

PMID- 15940312
TI  - [Glutamate, glutamine and ischaemia in the central nervous system].
AB  - BACKGROUND: This review presents basic knowledge on glutamate and glutamine
      homeostasis in the central nervous system and relates this knowledge to some
      aspects of cerebral ischaemia. RESULTS AND INTERPRETATION: The amino acid
      glutamate is the main excitatory neurotransmitter in the central nervous system.
      Following stimulation of the postsynaptic glutamate receptors, glutamate must
      rapidly be removed from the synaptic cleft. Whereas several other
      neurotransmitters are taken up directly into the presynaptic nerve terminal,
      glutamate is mainly transported into the surrounding glial cells. Glial glutamate
      can be amidated to glutamine, and since glutamine is a precursor of glutamate
      without being a neurotransmitter itself, it can be returned to the presynaptic
      neuron without eliciting new synaptic signals. In the nerve terminal, glutamine
      can be converted back to glutamate, thereby completing the postulated glutamate
      glutamine cycle. During ischaemia, this cycle is impaired as it depends on energy
      consuming membrane transport proteins and enzymes.

PMID- 15940313
TI  - [Treatment of burns in general practice].
AB  - Smaller burns for which wound management is uncomplicated are mostly treated by
      general practitioners. However, general practitioners working in locations far
      from a hospital need skills in primary assessment and management of larger burns
      as well. For burns with limited depth and surface area it is recommended to
      choose a polyurethane dressing when the wound is exudative. As the wound dries
      up, a hydrocolloid dressing is preferable. Close follow up is important. A
      limited infection should be treated with silver sulfadiazine or a silver
      dressing. Hospital admittance is required for patients with deep wounds in the
      face, on the hands or in the genital area, high voltage burns and inhalation
      injuries, and of children below the age of two.

PMID- 15940314
TI  - [General practitioner-based prehospital thrombolysis in acute myocardial
      infarction].
AB  - BACKGROUND: If properly organised, prehospital thrombolysis in acute myocardial
      infarction saves time to treatment and improves outcome. We have evaluated a
      quality assurance program for general practitioner-based (GP-based) prehospital
      thrombolysis. MATERIAL AND METHODS: GPs and the local ambulance service in eight
      local communities went through a one-day training programme. The GPs interpreted
      the ECGs themselves and initiated prehospital thrombolysis according to a set of
      criteria. Patients with prehospital thrombolysis were prospectively compared with
      patients receiving hospital thrombolysis during the same time period. RESULTS:
      From 1999 to 2001, 69 patients received prehospital thrombolysis: 50% of all
      patients receiving thrombolysis. No complications were attributed to prehospital
      administration; 66 out of 69 patients received thrombolysis on a correct
      indication. The median call to needle time was reduced from 145 to 63 minutes in
      patients treated before arrival at a hospital, which gives a median of 82 minutes
      of time saved. INTERPRETATION: GP-initiated prehospital thrombolysis is safe
      after proper training and saves clinically important time to treatment compared
      with hospital administration.

PMID- 15940315
TI  - [Vaccination against allergy--why and how].

PMID- 15940316
TI  - [Oral care in the last stages of life].
AB  - BACKGROUND: It is the responsibility of the nursing homes to provide residents
      with adequate oral hygiene. This article describes a new approach to improve the
      oral hygiene standards of the elderly in long-term care. MATERIAL AND METHODS:
      The method was based on 1) the production of individual, pictorial oral care
      plans for each resident; 2) the patients receiving first-class dental care
      equipment (electric toothbrush, interdental brushes, prosthesis brushes etc.; 3)
      nursing staff receiving information on oral hygiene methods; 4) the introduction
      of a number of fixed routines at the nursing home. To assess the oral care in the
      group of elderly, the mucosal-plaque index was used. RESULTS AND INTERPRETATION:
      The evaluation was made before commencement of the study and again after 15
      months. The evaluation showed that the introduction of this method significantly
      improved oral hygiene in 40 out of the 63 patients.

PMID- 15940317
TI  - [Therapeutic use of music in nursing homes].
AB  - BACKGROUND: There is growing interest in the therapeutic use of music in nursing
      homes. The difficulties inherent in medical treatment of this population warrant
      further studies of music as a therapeutic modality. MATERIAL AND METHODS: This is
      a review of articles on the use of music and music therapy in geriatrics.
      Findings from a nursing home project, "Music in the late stages of life", have
      been compared with those reported in the literature, particularly from meta
      analyses and systematic reviews. The distinction between music therapy, music
      medicine and individualised music has been taken into account. RESULTS AND
      INTERPRETATION: The evidence base for using music therapeutically in nursing
      homes is still insufficient. There is a lack of consensus about criteria for the
      use of different types of music therapy, and most studies have methodological
      limitations or are insufficiently defined. Approaches to measurement and
      evaluation vary. Meta-analyses have tried to overcome this problem by emphasizing
      effect size. A widely shared conclusion is that music can supplement medical
      treatment. The cost is low, there are few side effects, and music gives a high
      level of patient satisfaction. Clinical experience and analyses of effect size
      indicate that music has a specific potential in nursing homes. It can enhance
      well-being and alleviate symptoms like agitation, anxiety, depression, and
      sensomotor symptoms in neurodegenerative diseases; it may also contribute in
      palliative care at the end-of-life stage.

PMID- 15940318
TI  - [Behavioural and psychological symptoms in dementia].
AB  - BACKGROUND: Behavioural and psychological symptoms in dementia (BPSD) are the
      clinically most significant symptoms of the illness. They are non-cognitive and
      include apathy, agitation, aggression, anxiety, hallucinations and delusions. The
      syndrome is not well defined, and the symptomatology is heterogenous. MATERIALS
      AND METHODS: This discussion of the concept of BPSD, which suggest assessment and
      treatment strategies, is based on a review of the literature as well as on
      clinical experience and knowledge of clinical practice in the field in Norway.
      RESULTS AND INTERPRETATION: BPSDs are widespread and often critical with regard
      to life quality for the patient as well as caregiver stress. The frequency of
      BPSD increases as the dementing disorder progresses. There are several
      etiological factors that require thorough assessment of biological,
      psychological, and environmental issues. The treatment should be aimed at well
      defined symptoms. Pharmacological treatment is widely used, though there is
      limited evidence of the benefit. Non-pharmacological treatment should be the
      first choice for milder symptoms of BPSD.

PMID- 15940320
TI  - [Medical publishing in Norway 1905-2005].
AB  - The nation-building process in Norway took mainly place before the Norwegian
      Swedish union came to a close in 1905. This was not a dramatic change, though the
      end of the union did bring a lift to Norwegian national consciousness. In 1905
      there were three general medical journals in Norway and approximately 1200
      doctors. German was the most important language of international science, but
      most scientific publishing was done in Norwegian. After the Second World War,
      English became the dominating language of scientific communication. Twentieth
      century medicine and medical publishing was an era of specialisation and
      internationalisation. Norwegian medicine has to a large extent been
      internationalised through Nordic cooperation, with the Nordic specialist journals
      being of particular importance. With increasing professionalism in research,
      international English-language journals have become the major channels of
      communication, though several Norwegian-language journals (on paper or on the
      internet) have been established and are of crucial importance to a national
      identity within medical specialties. In 2005 there is only one general medical
      journal in Norwegian, in a country with approximately 20,000 doctors. A national
      identity related to medical publishing is not given much attention, though
      national medicine is still closely tied in with national culture. Good clinical
      practice should be based on a firm knowledge of local society and local
      tradition. This is a challenge in contemporary medical publishing.

PMID- 15940319
TI  - [Specialised short-term wards in nursing homes--the Trondheim model].
AB  - BACKGROUND: The health sector faces major challenges as a consequence of the
      elderly constituting a growing proportion of the population. Doctors at all
      levels will need to acquire the skills needed for dealing with patients with
      multiple and complex conditions, and hospitals will need to be dynamic in dealing
      with patients with acute and curable diseases as well as with the elderly and
      chronically ill. There is a considerable professional gap between community care
      services and services offered by the general hospitals. MATERIAL AND METHODS: In
      the City of Trondheim, Norway, the community care and hospital services have
      analysed the challenges they share and what they can do to make the "chain of
      care" better for those patients that are the most in need of coordinated efforts.
      One initiative is two short-term units specialising in treatment and care at an
      intermediary level between ordinary nursing homes and hospitals. RESULTS: In
      2003, 275 patients were admitted to the intermediary care department in Sobstad
      nursing home, and at Havstein nursing home 79 patients were admitted to its
      palliative care department. The operating costs in these nursing homes are higher
      than in traditional units, but far lower than in hospitals. We suggest that these
      specialised units represent a good solution, professionally as well as
      financially.

PMID- 15940321
TI  - [A Swedish helping hand].

PMID- 15940322
TI  - [Norwegian-Swedish labor market for physicians].

PMID- 15940323
TI  - [Time for a more intensive Swedish-Norwegian research cooperation].

PMID- 15940324
TI  - [Norwegian pediatrician in Sweden and Swedish pediatrician in Norway].

PMID- 15940325
TI  - [Microbiology on Kjolen's both sides].

PMID- 15940326
TI  - [Waiting lists in the neighbouring country].

PMID- 15940329
TI  - [Norwegian physicians' North Cape-Varanger expedition in 1905].

PMID- 15940331
TI  - [Italian geriatrics].

PMID- 15940332
TI  - [Sexual relations between physicians and patients are not acceptable].

PMID- 15940333
TI  - [Asylum seekers who received final refusal from immigration authorities].

PMID- 15940334
TI  - [A national competence center for breast feeding--beneficial for physicians?].

PMID- 15940335
TI  - The phenomenon of alcohol (and other drugs) use in pregnancy.

PMID- 15940336
TI  - [Registration of anal incontinence].

PMID- 15940337
TI  - [What dosage of antidiabetics?].

PMID- 15940338
TI  - [Fetal injury and alcohol drinking during pregnancy].

PMID- 15940340
TI  - [Quisling].

PMID- 15940343
TI  - Beta-actin in human colon adenocarcinoma cell lines with different metastatic
      potential.
AB  - Human colon adenocarcinoma LS180 parental cell line and selected variants,
      characterized by different metastatic capacity were used to examine, whether a
      correlation exists between beta-actin expression, its subcellular distribution
      and metastatic potential of these cells. Cytosolic fraction (supernatant 105000 x
      g), isolated from the tumor cells was used as a source for actin quantification.
      The higher level of beta-actin was observed in the cytosol of three selected
      sublines to compare with LS180 parental line. Statistically significant increase
      of beta-actin level in highly motile EB3 cells variant should be underlined to
      compare with the other sublines. Distinct differences in the phenotype of
      adenocarcinoma cell variants were found, such as the changes in cells shape,
      cells spreading and ability to attach to the surface of culture dish. Actin
      cytoskeleton was visualized with fluorescence microscopy application and
      microfilaments rhodamine-conjugated phalloidin staining. beta-actin subcellular
      localization was done by immunofluorescence staining with monoclonal anti-beta
      actin antibodies. In the elongated cells (LS180, 3LNLN), this isoactin is
      dispersed in the whole cell body and concentrates in pseudopods and at the
      leading edges, when in the rounded variant (EB3) beta-actin dominates mainly in
      cortical ring under cellular membrane and it is also seen in the subtle
      protrusions. Summary of our former (Nowak et al., 2002, Acta Biochim. Polon., 49:
      823) and current data lead to the conclusion that there is a distinct correlation
      between metastatic capacity of examined human colon adenocarcinoma cells, the
      state of actin polymerization, actin cytoskeleton organization and beta-actin
      expression.

PMID- 15940344
TI  - Adeno-associated virus vector-mediated gene delivery to the vasculature and
      kidney.
AB  - Relatively successful elsewhere, gene delivery aimed at the vasculature and
      kidney has made very little progress. In the kidney, the hurdles are related to
      the unique structure-function relationships of this organ and in the blood
      vessels to a variety of, mostly endothelial, factors making the delivery of
      transgenes very difficult. Among gene-therapeutic approaches, most viral gene
      delivery systems utilized to date have shown significant practical and safety
      related limitations due to the level and duration of recombinant transgene
      expression as well as their induction of a significant host immune response to
      vector proteins. Recombinant adeno-associated virus (rAAV) vectors appear to
      offer a vehicle for safe, long-term transgene expression. rAAV-based vectors are
      characterized by a relative non-immunogenicity and the absence of viral coding
      sequences. Furthermore, they allow for establishment of long-term latency without
      deleterious effects on the host cell. This brief review addresses problems
      related to transgene-delivery to kidney and vasculature with particular attention
      given to rAAV vectors. The potential for gene therapy as a strategy for selected
      renal and vascular diseases is also discussed.

PMID- 15940345
TI  - Targeting site-specific chromosome integration.
AB  - The concept of gene therapy was introduced with great promise and high
      expectations. However, what appeared simple in theory has not translated into
      practice. Despite some success in clinical trials, the research community is
      still facing an old problem: namely, the need for a vector that can deliver a
      gene to target cells without adverse events while maintaining a long-term
      therapeutic effect. Some of these challenges are being addressed by the
      development of hybrid vectors which meld two different viral systems to
      incorporate efficient gene delivery and large cloning capacity with site-specific
      integration. The two known systems that integrate genes into specific sites in
      mammalian genomes are the adeno-associated virus and phage integrases. Recent
      experiments with hybrid vectors incorporating both of these systems are
      encouraging. However, extensive research should be directed towards the safety
      and efficacy of this approach before it will be available for gene therapy.

PMID- 15940346
TI  - Inhibition and regression of atherosclerotic lesions.
AB  - Atherosclerosis, once believed to be a result of a slow, irreversible process
      resulting from lipid accumulation in arterial walls, is now recognized as a
      dynamic process with reversibility. Liver-directed gene therapy for dyslipidemia
      aims to treat patients who are not responsive to currently available primary and
      secondary prevention. Moreover, gene therapy strategies have also proved valuable
      in studying the dynamics of atherosclerotic lesion formation, progression, and
      remodeling in experimental animals. Recent results on the long-term effect of
      gene therapy suggest that hepatic expression of therapeutic genes suppresses
      inflammation and has profound effects on the nature of the atherogenic process.

PMID- 15940347
TI  - Characterization of a novel protein that specifically binds to DNA modified by N
      acetoxy-acetylaminofluorene and cis-diamminedichloroplatinum.
AB  - Proteins recognizing DNA damaged by the chemical carcinogen N-acetoxy
      acetylaminofluorene (AAAF) were analyzed in nuclear extracts from rat tissues,
      using a 36 bp oligonucleotide as a substrate and electrophoretic mobility shift
      and Southwestern blot assays. One major damage-recognizing protein was detected,
      whose amount was estimated as at least 10(5) copies per cell. Levels of this
      protein were similar in extracts from brain, kidney and liver, but much lower in
      extracts from testis. The affinity of the detected protein for DNA damaged by
      AAAF was about 70-fold higher than for undamaged DNA. DNA damaged by cis
      diamminedichloroplatinum (cis-DDP), benzo(a)pyrene diolepoxide (BPDE) or UV
      radiation also bound this protein with an increased affinity, the former more
      strongly and the latter two more weakly as compared to AAAF-damaged DNA. The
      detected AAAF/DDP-damaged-DNA-binding (AAAF/DDP-DDB) protein had a molecular mass
      of about 25 kDa and was distinct from histone H1 or HMGB proteins, which are
      known to have a high affinity for cis-DDP-damaged DNA. The level of this damage
      recognizing protein was not affected in rats treated with the carcinogen 2
      acetylaminofluorene. The activity of an AAAF/DDP-DDB protein could also be
      detected in extracts from mouse liver cells but not from the Hep2G human
      hepatocellular carcinoma.

PMID- 15940348
TI  - Role of NAD(P)H:quinone oxidoreductase (NQO1) in apoptosis induction by
      aziridinylbenzoquinones RH1 and MeDZQ.
AB  - We aimed to characterize the role of NAD(P)H:quinone oxidoreductase (NQO1) in
      apoptosis induction by antitumour quinones RH1 (2,5-diaziridinyl-3-hydroxymethyl
      6-methyl-1,4-benzoquinone) and MeDZQ (2,5-dimethyl-3,6-diaziridinyl-1,4
      benzoquinone). Digitonin-permeabilized FLK cells catalyzed NADPH-dependent single
      and two-electron reduction of RH1 and MeDZQ. At equitoxic concentrations, RH1
      and MeDZQ induced apoptosis more efficiently than the nonalkylating duroquinone
      or H(2)O(2). The antioxidant N,N'-diphenyl-p-phenylene diamine, desferrioxamine,
      and the inhibitor of NQO1 dicumarol, protected against apoptosis induction by all
      compounds investigated, but to a different extent. The results of multiparameter
      regression analysis indicate that RH1 and MeDZQ most likely induce apoptosis via
      NQO1-linked formation of alkylating species but not via NQO1-linked redox
      cycling.

PMID- 15940349
TI  - Isolation and characterization of pigeon breast muscle cytosolic 5'-nucleotidase
      I (cN-I).
AB  - 5'-Nucleotidase specific towards dCMP and AMP was isolated from avian breast
      muscle and characterized. It was found to be similar to a type-I form (cN-I)
      identified earlier as the AMP-selective 5'-nucleotidase responsible for adenosine
      formation during ATP breakdown in transfected COS-7 cells. Expression pattern of
      the cN-I gene in pigeon tissues indicated breast muscle as a rich source of the
      transcript. We purified the enzyme from this source using two-step chromatography
      and obtained an active homogenous preparation, free of ecto-5'-nucleotidase
      activity. The tissue content of the activity was calculated at 0.09 U/g wet
      weight. The specific activity of the enzyme preparation was 4.33 U/mg protein and
      it preferred dCMP and AMP to dAMP and IMP as a substrate. Its kinetic properties
      were very similar to those of the enzyme purified earlier from heart tissue. It
      was strongly activated by ADP. Inhibition by inorganic phosphate was more
      pronounced than in heart-isolated cN-I. Despite this difference, a similar
      physiological function is suggested for cN-I in both types of muscle.

PMID- 15940350
TI  - Recombinant angioarrestin secreted from mouse melanoma cells inhibits growth of
      primary tumours.
AB  - Angioarrestin is a recently described anti-angiogenic protein whose expression is
      down-regulated in solid tumours of various origins. It has a sequence identical
      to angiopoietin related protein-1. In this study we investigated anti-tumour
      properties of angioarrestin in B16 (F10) melanoma tumour model. We constructed an
      expression vector encoding human angioarrestin under the control of EF-1alpha
      promoter. This vector was transferred to B16 (F10) cells and recombinant
      angioarrestin secreted from the transfected cells was tested for anti-angiogenic
      activity using endothelial cell proliferation assay. Finally, mice were injected
      subcutaneously with cells that had been transfected with either angioarrestin
      encoding vector or empty vector and tumor growth was compared. The obtained
      recombinant angioarrestin inhibited proliferation of bovine aortic endothelial
      cells. Tumours derived from an angioarrestin-secreting B16 (F10) cell clone grew
      in vivo more slowly than tumours derived from a cell clone transfected with empty
      vector. These data show, to our knowledge for the first time, that angioarrestin
      can inhibit primary melanoma tumour growth.

PMID- 15940351
TI  - Two types of non-homologous RNA recombination in brome mosaic virus.
AB  - Non-homologous RNA recombination is a process enabling the exchange of genetic
      material between various (related or unrelated) RNA-based viruses. Despite
      extensive investigations its molecular mechanism remains unclear. Studies on
      genetic recombination in brome mosaic virus (BMV) have shown that local
      hybridization between genomic RNAs induces frequent non-homologous crossovers. A
      detailed analysis of recombinant structures suggested that local complementary
      regions might be involved in two types of non-homologous recombination in BMV:
      site-specific and heteroduplex-mediated. To verify the above hypothesis and
      better recognize the mechanism of the phenomenon studied we have tested how the
      putative types of recombination are affected by a specific mutation in the BMV
      polymerase gene or by changes in RNA structure. The experiments undertaken
      revealed substantial differences between site-specific and heteroduplex-mediated
      recombination, indicating that they occur according to different mechanisms. The
      former can be classified as homology-assisted, and the latter as homology
      independent. In addition to local RNA/RNA hybridization, short regions of
      homology are required for site-specific crossovers to occur. They are most
      efficiently mediated if one homologous sequence is located at the beginning of
      and the second just before a double-stranded region. At present it is difficult
      to state what is the mechanism of heteroduplex-mediated recombination. Earlier it
      was postulated that strong RNA/RNA interaction enforces template switching by the
      viral replicase. There are, however, several observations questioning this model
      and indicating that some other factors, which are still unknown, may influence
      heteroduplex-mediated crossovers.

PMID- 15940352
TI  - Some structural properties of plant serine:glyoxylate aminotransferase?
AB  - The structural properties of photorespiratory serine:glyoxylate aminotransferases
      (SGAT, EC 2.6.1.45) from maize (Zea mays L.) and wheat (Triticum aestivum L.)
      leaves were examined. By means of molecular sieving on Zorbax SE-250 column and
      filtration through centrifugal filters it was shown that dimers of wheat enzyme
      (molecular mass of about 90 kDa) dissociate into component monomers (molecular
      mass of about 45 kDa) upon decrease in pH value (from 9.1 or 7.0 to 6.5). At pH
      9.1 a 50-fold decrease of ionic strength elicited a similar effect. Under the
      same conditions homodimers of the maize enzyme (molecular mass similar to that of
      the wheat enzyme) remained stable. Immunoblot analysis with polyclonal antiserum
      against wheat seedling SGAT on leaf homogenates or highly purified preparations
      of both enzymes showed that the immunogenic portions of the wheat enzyme are
      divergent from those of the maize enzyme. The sequence of 136 amino acids of the
      maize enzyme and 78 amino acids of the wheat enzyme was established by tandem
      mass spectrometry with time of flight analyzer. The two enzymes likely share
      similarity in tertiary and quaternary structures as well as high level of
      hydrophobicity on their molecular surfaces. They likely differ in the mechanism
      of transport from the site of biosynthesis to peroxisomes as well as in some
      aspects of secondary structure.

PMID- 15940353
TI  - Exact relevance of bone marrow cells in the healing process after myocardial
      infarction: analysis with a murine model of bone marrow cell transplantation.
AB  - BACKGROUND: Cellular cardiomyoplasty has created new possibilities in cardiac
      regeneration. Several cell types can be used in the procedure, such as skeletal
      myoblasts and bone marrow cells. Recent publications have suggested that bone
      marrow cells may be excellent candidates due to their pluripotency, but their
      actual role in cardiac regeneration is unknown. OBJECTIVE: To evaluate the exact
      physiological role of bone marrow cells in the healing process after myocardial
      infarction. METHODS: A mouse bone marrow cell transplantation model was used in
      which transplanted cells were easily detectable by immunohistochemistry. Chimeric
      mice were subjected to myocardial infarction by ligation of the left descending
      coronary artery. After one month, the mice were sacrificed and the scars were
      analyzed. RESULTS: Transplanted bone marrow cells were detected in the scars and
      these cells seemed able to transdifferentiate into endothelial cells, but no
      transdifferentiation into cardiomyocytes occurred. This mechanism of regeneration
      was dismissed because only 2% of the vessels in the scars were positive for
      transplanted cells. CONCLUSIONS: Bone marrow cells might be involved in
      myocardial healing, but this physiological mechanism is insufficient to allow
      correct regeneration.

PMID- 15940354
TI  - Have angiotensin receptor blockers lived up to expectations?
AB  - Angiotensin receptor blockers (ARBs) were introduced after clinical trials showed
      angiotensin-converting enzyme inhibitors (ACEIs) to have extensive clinical
      benefits in a wide range of diseases. Consequently, it has been more difficult
      for clinical trials to demonstrate similar, enhanced or additive benefits of
      ARBs. However, ARBs were introduced with the hypothesis that they were likely a
      more effective method of interrupting the renin-angiotensin system and would
      result in enhanced outcomes. Clinical trials in high-risk vascular patients
      (after myocardial infarction), patients with heart failure and patients with
      nephropathy show the benefits of ACE inhibition. ARBs likely have similar
      benefits as ACEIs when used after myocardial infarction, in patients with heart
      failure and for management of diabetic nephropathy. However, ARBs generally
      remain a second-line treatment because it has been more difficult to demonstrate
      that ARBs prevent acute vascular events, such as myocardial infarction, together
      with the greater clinical trial evidence for ACE inhibition. The primary
      application of ACEIs over ARBs is reflected in the Canadian clinical guidelines
      for the management of patients with diabetes, hypertension, heart failure and
      following myocardial infarction. Until the completion of clinical trials, such as
      the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint
      Trial (ONTARGET), that examine whether ARBs have vascular protective properties
      similar to ACEIs, it is unlikely that the clinical guidelines will change.

PMID- 15940355
TI  - Inhibition of the renin-angiotensin system in cardiovascular protection: Is it
      important to watch your C'ARB' intake?

PMID- 15940356
TI  - The efficacy of sirolimus- and paclitaxel-eluting stents: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Drug-eluting stents prevent in-stent restenosis after percutaneous
      coronary intervention, and differences between sirolimus-eluting stents (SES) and
      paclitaxel-eluting stents (PES) may exist in the rates of target lesion
      revascularization, death, myocardial infarction and stent thrombosis. OBJECTIVE:
      To compare the efficacy of SES and PES with the efficacy of bare-metal stents for
      de novo coronary lesions in patients with stable or unstable angina. METHODS: A
      meta-analysis of randomized trials from MEDLINE, EMBASE and other electronic
      databases and conference proceedings was conducted. The efficacy of SES, PES with
      a polymer carrier (PPOL) and PES without a polymer carrier (PNPOL) was compared
      using random-effects models. RESULTS: Ten trials comprising 5041 patients were
      included in the meta-analysis. There was an absolute decrease in target lesion
      revascularization of 17% (95% CI 14% to 20%), 9% (95% CI 6% to 11%) and 3% (95%
      CI 0% to 6%) with SES, PPOL and PNPOL, respectively, with significant differences
      between SES and PPOL and between PPOL and PNPOL (P < 0.01 for both comparisons).
      However, sensitivity analysis using the OR of target lesion revascularization
      showed no difference between SES (OR 0.18 [95% CI 0.12 to 0.26]) and PPOL (OR
      0.25 [95% CI 0.16 to 0.37]) (P = 0.26). There were no differences in the
      incidence of death, myocardial infarction or stent thrombosis, although the small
      number of events limited the power of these analyses. CONCLUSIONS: SES show a
      greater absolute reduction in target lesion revascularization than do PES, likely
      due to differences in the bare-metal stents used for comparison in the trials.
      Head-to-head comparisons are needed to directly address the differential efficacy
      of SES and PES.

PMID- 15940357
TI  - Awareness and misconception of hypertension in Canada: results of a national
      survey.
AB  - BACKGROUND: The Canadian Heart Health Surveys were the last Canadian population
      based physical measures surveys (conducted between 1988 and 1992) that determined
      that hypertension in Canada was poorly managed. Hypertension was undetected in
      almost one-half of all hypertensive Canadians surveyed, and only 13% of those
      with hypertension were treated and controlled to recommended blood pressure
      targets. The reasons for poor control are likely multifactorial; however, a lack
      of public awareness and understanding of hypertension may contribute to the
      epidemic of uncontrolled hypertension in Canada. METHODS: A national telephone
      survey was conducted comprising 1001 randomly selected men and women older than
      40 years of age to determine the level of public awareness, understanding and
      misconception of hypertension in Canada. The survey was balanced for region, age
      and sex. RESULTS: Thirty-four per cent of respondents had been diagnosed with
      high blood pressure or hypertension by a health care professional, but only 58%
      of respondents had ever discussed their blood pressure with a physician, and only
      44% were able to identify their own blood pressure or differentiate blood
      pressure levels considered to be above or below recommended targets. Overall,
      respondents had a poor understanding of the consequences of high blood pressure
      or hypertension. The majority were unaware of the association between
      hypertension and heart disease (80%), heart attack (66%), kidney disease (98%),
      damage to blood vessels (95%) and premature death (74%). Respondents also had
      limited knowledge of lifestyle issues affecting hypertension, despite 44%
      indicating that they were overweight and 18% identifying themselves as smokers.
      Almost two-thirds (63%) thought hypertension had clearly identifiable signs or
      symptoms, although they believed that hypertension was not a serious medical
      condition. Most respondents (59%) falsely believed that they would not develop
      hypertension and 38% thought that they would be able to control hypertension
      without the aid of a physician if they did have hypertension. CONCLUSIONS: While
      hypertension-related complications are preventable, lack of public awareness and
      misconceptions about hypertension and hypertensive complications are common and
      may, in part, be associated with ongoing inadequate Canadian awareness, treatment
      and control rates for hypertension. Increasing public awareness of hypertension
      using public education and health provider strategies should be a high national
      health priority.

PMID- 15940358
TI  - Downward delegation of implantable cardioverter defibrillator decision-making in
      a restricted-resource environment: the pitfalls of bedside rationing.
AB  - Implantable cardioverter defibrillators have been shown to reduce all-cause
      mortality in some patient populations at risk of sudden death. New Canadian
      guidelines recommend implantable cardioverter defibrillator therapy for these
      patients. However, the need for these devices exceeds the funded volumes in many
      Canadian jurisdictions. As a result, rationing of this resource has been
      necessary. While rationing at the macro (Ministry of Health) and meso (hospital)
      levels has achieved some level of acceptance by society, the responsibility for
      the decisions taken at the micro (individual) patient level actually rests with
      the physician at the bedside. This 'bedside rationing' creates a moral dilemma
      for physicians, who are torn between their traditional fiduciary role as 'patient
      advocate' and the competing role of 'gatekeeper'. This 'downward delegation' of
      rationing decision-making obscures the reality that rationing occurs, and
      encourages covert, opaque and inconsistent approaches. The remedy is the
      development of fair, legitimate procedures for making rationing decisions that
      include guidelines that structure and constrain those decisions. Macro- and meso
      level stakeholders must also recognize and take responsibility for their part in
      restricting resources in a broadly inclusive and transparent process.

PMID- 15940359
TI  - Kawasaki disease, myocardial infarction and coronary artery revascularization.
AB  - Kawasaki disease (KD) is the leading cause of acquired pediatric heart disease in
      North America and Japan. Cardiac sequelae, such as coronary artery aneurysms and
      myocardial infarction, are the major causes of the morbidity and mortality
      associated with KD. Three case scenarios are described illustrating the wide
      range of clinical presentations of myocardial ischemia in children after acute
      KD, varying from asymptomatic to fatal myocardial infarction. In addition, the
      present paper provides a review of the literature on myocardial infarction in
      association with KD and various modalities of coronary artery revascularization
      in children with myocardial ischemia secondary to KD.

PMID- 15940360
TI  - In silico modeling and simulation of bone biology: a proposal.
AB  - Contemporary, computer-based mathematical modeling techniques make it possible to
      represent complex biological mechanisms in a manner that permits hypothesis
      testing in silico. This perspective shows how such approaches might be applied to
      bone remodeling and therapeutic research. Currently, the dominant conceptual
      model applied in bone research involves the dynamic balance between the continual
      build-up and breakdown of bone matrix by two cell types, the osteoblasts and
      osteoclasts, acting together as a coordinated, remodeling unit. This
      conceptualization has served extraordinarily well as a focal point for
      understanding how mutations, chemical mediators, and mechanical force, as well as
      external influences (e.g., drugs, diet) affect bone structure and function.
      However, the need remains to better understand and predict the consequences of
      manipulating any single factor, or combination of factors, within the context of
      this complex system's multiple interacting pathways. Mathematical models are a
      natural extension of conceptual models, providing dynamic, quantitative
      descriptions of the relationships among interacting components. This
      formalization creates the ability to simulate the natural behavior of a system,
      as well as its modulation by therapeutic or dietetic interventions. A number of
      mathematical models have been developed to study complex bone functions, but most
      include only a limited set of biological components needed to address a few
      specific questions. However, it is possible to develop larger, multiscale models
      that capture the dynamic interactions of many biological components and relate
      them to important physiological or pathological outcomes that allow broader
      study. Examples of such models include entelos' physiolab platforms. These models
      simulate the dynamic, quantitative interactions among a biological system's
      biochemicals, cells, tissues, and organs and how they give rise to key
      physiologic and pathophysiologic outcomes. We propose that a similar predictive,
      dynamical, multiscale mathematical model of bone remodeling and metabolism would
      provide a better understanding of the mechanisms governing these phenomena as
      well as serve as an in silico platform for testing pharmaceutical and clinical
      interventions on metabolic bone disease.

PMID- 15940361
TI  - Ovariectomy-induced bone loss varies among inbred strains of mice.
AB  - There is a subset of women who experience particularly rapid bone loss during and
      after the menopause. However, the factors that lead to this enhanced bone loss
      remain obscure. We show that patterns of bone loss after ovariectomy vary among
      inbred strains of mice, providing evidence that there may be genetic regulation
      of bone loss induced by estrogen deficiency. INTRODUCTION: Both low BMD and
      increased rate of bone loss are risk factors for fracture. Bone loss during and
      after the menopause is influenced by multiple hormonal factors. However, specific
      determinants of the rate of bone loss are poorly understood, although it has been
      suggested that genetic factors may play a role. We tested whether genetic factors
      may modulate bone loss subsequent to estrogen deficiency by comparing the
      skeletal response to ovariectomy in inbred strains of mice. MATERIALS AND
      METHODS: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ,
      CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery
      (n = 6-9/group). After 1 month, mice were killed, and microCT was used to compare
      cortical and trabecular bone response to OVX. RESULTS: The effect of OVX on
      trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular
      bone volume (BV/TV) declined after OVX in all strains (-15 to -24%), except for
      C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline
      in trabecular BV/TV (-39%) than C57BL/6J (-18%), DBA2/J (-23%), and CAST/EiJ mice
      (-21%). OVX induced declines in cortical bone properties, but in contrast to
      trabecular bone, the effect of OVX did not vary by mouse strain. The extent of
      trabecular bone loss was greatest in those mice with highest trabecular BV/TV at
      baseline, whereas cortical bone loss was lowest among those with high cortical
      bone parameters at baseline. CONCLUSIONS: We found that the skeletal response to
      OVX varies in a site- and compartment-specific fashion among inbred mouse
      strains, providing support for the hypothesis that bone loss during and after the
      menopause is partly genetically regulated.

PMID- 15940362
TI  - Interleukin-11 receptor signaling is required for normal bone remodeling.
AB  - IL-6 and -11 regulate bone turnover and have been implicated in estrogen
      deficiency-related bone loss. In this study, deletion of IL-11 signaling, but not
      that of IL-6, suppressed osteoclast differentiation, resulting in high trabecular
      bone volume and reduced bone formation. Furthermore, IL-11 signaling was not
      required for the effects of estradiol or estrogen deficiency on the mouse
      skeleton. INTRODUCTION: Interleukin (IL)-6 and -11 stimulate osteoclastogenesis
      and bone formation in vitro and have been implicated in bone loss in estrogen
      deficiency. Because of their common use of the gp130 co-receptor signaling
      subunit, the roles of these two cytokines are linked, and each may compensate for
      the absence of the other to maintain trabecular bone volume and bone cell
      differentiation. MATERIALS AND METHODS: To determine the interactions in bone
      between IL-11 and IL-6 in vivo and whether IL-11 is required for normal bone
      turnover, we examined the bone phenotype of mature male and female IL-11 receptor
      knockout mice (IL-11Ralpha1-/-) and compared with the bone phenotype of IL-6-/-
      mice and mice lacking both IL-6 and IL-11Ralpha. To determine whether IL-11 is
      required for the effects of estrogen on trabecular bone, mature IL-11Ralpha1-/-
      mice were ovariectomized and treated with estradiol. RESULTS: In both male and
      female IL-11Ralpha1-/- mice, trabecular bone volume was significantly higher than
      that of wildtype controls. This was associated with low bone resorption and low
      bone formation, and the low osteoclast number generated by IL-11Ralpha1-/-
      precursors was reproduced in ex vivo cultures, whereas elevated osteoblast
      generation was not. Neither trabecular bone volume nor bone turnover was altered
      in IL-6-/- mice, and compound IL-6-/- :IL-11Ralpha1-/- mice showed an identical
      bone phenotype to IL-11Ralpha1-/- mice. The responses of IL-11Ralpha1-/- mice to
      ovariectomy and estradiol treatment were the same as those observed in wildtype
      mice. CONCLUSIONS: IL-11 signaling is clearly required for normal bone turnover
      and normal trabecular bone mass, yet not for the effects of estradiol or estrogen
      deficiency on the skeleton. In the absence of IL-11Ralpha, increased trabecular
      bone mass seems to result from a cell lineage-autonomous reduction in osteoclast
      differentiation, suggesting a direct effect of IL-11 on osteoclast precursors.
      The effects of IL-11Ralpha deletion on the skeleton are not mediated or
      compensated for by changes in IL-6 signaling.

PMID- 15940363
TI  - TOPGAL mice show that the canonical Wnt signaling pathway is active during bone
      development and growth and is activated by mechanical loading in vitro.
AB  - We identified cellular targets of canonical Wnt signaling within the skeleton,
      which included chondrocytes, osteoblasts, and osteocytes in growing bone, but
      only osteocytes and chondrocytes in the mature skeleton. Mechanical deformation
      induced Wnt signaling in osteoblasts in vitro. INTRODUCTION: Genetic evidence in
      mice and humans has implicated the canonical Wnt signaling pathway in the control
      of skeletal development and bone mass. However, little is known of the details of
      Wnt signaling in the skeleton in vivo. We used Wnt indicator TOPGAL mice to
      identify which cells activated this pathway during bone development and in the
      mature skeleton. MATERIALS AND METHODS: We examined canonical Wnt signaling
      during embryonic and neonatal bone development in TOPGAL mice. The TOPGAL
      transgene consists of a beta-galactosidase gene driven by a T cell factor
      (TCF)beta-catenin responsive promoter so that canonical Wnt activity can be
      detected by X-gal staining. Expression of Wnt signaling components was examined
      in primary calvarial cell cultures by RT-PCR. The effect of mechanical
      deformation on Wnt signaling was examined in primary calvarial cells grown on
      collagen I and stretched using Flexercell Tension Plus System FX-4000T.
      Immunohistochemistry was used to examine the localization of beta-catenin in
      cartilage, bone, and cultured calvarial cells exposed to physical deformation.
      RESULTS AND CONCLUSIONS: Canonical Wnt signaling was active in several cell types
      in the fetal and neonatal skeleton, including chondrocytes, osteoblasts, and
      osteocytes. With age, activation of Wnt signaling became less prominent but
      persisted in chondrocytes and osteocytes. Although osteoblasts in culture
      expressed many different individual Wnt's and Wnt receptors, the TOPGAL transgene
      was not active in these cells at baseline. However, Wnt signaling was activated
      in these cells by physical deformation. Together with the activation of canonical
      Wnt signaling in osteocytes seen in vivo, these data suggest that Wnt signaling
      may be involved in the coupling of mechanical force to anabolic activity in the
      skeleton.

PMID- 15940364
TI  - Angiogenesis is required for successful bone induction during distraction
      osteogenesis.
AB  - The role of angiogenesis during mechanically induced bone formation is
      incompletely understood. The relationship between the mechanical environment,
      angiogenesis, and bone formation was determined in a rat distraction osteogenesis
      model. Disruption of either the mechanical environment or endothelial cell
      proliferation blocked angiogenesis and bone formation. This study further defines
      the role of the mechanical environment and angiogenesis during distraction
      osteogenesis. INTRODUCTION: Whereas successful fracture repair requires a
      coordinated and complex transcriptional program that integrates
      mechanotransductive signaling, angiogenesis, and osteogenesis, the
      interdependence of these processes is not fully understood. In this study, we use
      a system of bony regeneration known as mandibular distraction osteogenesis (DO)
      in which a controlled mechanical stimulus promotes bone induction after an
      osteotomy and gradual separation of the osteotomy edges to examine the
      relationship between the mechanical environment, angiogenesis, and osteogenesis.
      MATERIALS AND METHODS: Adult Sprague-Dawley rats were treated with gradual
      distraction, gradual distraction plus the angiogenic inhibitor TNP-470, or acute
      distraction (a model of failed bony regeneration). Animals were killed at the end
      of distraction (day 13) or at the end of consolidation (day 41) and examined with
      muCT, histology, and immunohistochemistry for angiogenesis and bone formation (n
      = 4 per time-point per group). An additional group of animals (n = 6 per time
      point per group) was processed for microarray analysis at days 5, 9, 13, 21, and
      41. RESULTS AND CONCLUSIONS: Either TNP-470 administration or disruption of the
      mechanical environment prevented normal osteogenesis and resulted in a fibrous
      nonunion. Subsequent analysis of the regenerate showed an absence of angiogenesis
      by gross histology and immunohistochemical localization of platelet endothelial
      cell adhesion molecule in the groups that failed to heal. Microarray analysis
      revealed distinct patterns of expression of genes associated with osteogenesis,
      angiogenesis, and hypoxia in each of the three groups. Our findings confirm the
      interdependence of the mechanical environment, angiogenesis, and osteogenesis
      during DO, and suggest that induction of proangiogenic genes and the proper
      mechanical environment are both necessary to support new vasculature for bone
      induction in DO.

PMID- 15940365
TI  - Alpha-lipoic acid inhibits TNF-alpha-induced apoptosis in human bone marrow
      stromal cells.
AB  - TNF-alpha is an important mediator of bone loss. In the HS-5 hBMSC, TNF-alpha and
      H2O2 increased intracellular ROS levels and induced cell apoptosis through
      activation of caspases, JNK and NF-kappaB. alpha-Lipoic acid prevented these
      changes induced by TNF-alpha and H2O2, suggesting its potential therapeutic
      applications in attenuating bone loss. INTRODUCTION: Oxidative stress is an
      important mediator of bone loss. TNF-alpha, which plays a critical role in the
      bone loss after menopause, has been shown to increase intracellular oxidative
      stress. Because oxidative stress is associated with cell death, we analyzed the
      apoptotic effects of TNF-alpha and H2O2 on human bone marrow stromal cells
      (hBMSCs). We also examined the protective effects of an important biological
      thiol antioxidant, alpha-lipoic acid (alpha-LA), against TNF-alpha- and H2O2
      induced apoptosis. MATERIALS AND METHODS: Using the HS-5 hBMSC cell line, we
      tested whether TNF-alpha-induced apoptosis was mediated by the generation of
      excessive reactive oxygen species (ROS). Apoptosis was determined by 3-(4,5
      dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay, trypan blue
      exclusion assay, quantitation of histone-associated DNA fragments in cytosol, and
      the activation of caspases. The mechanisms mediating these apoptotic effects were
      determined by Western blotting and enzyme immunoassay. RESULTS: Both TNF-alpha
      and H2O2 increased intracellular ROS levels, reduced total cellular glutathione
      levels, activated caspases-3, -9, and -8, and enhanced hBMSC apoptosis. The
      activation of c-jun N-terminal kinase (JNK) and NF-kappaB mediated these
      apoptotic effects. Pretreatment of cells with alpha-LA prevented these changes
      induced by TNF-alpha and H2O2. CONCLUSIONS: Our data show that TNF-alpha
      increases intracellular ROS in hBMSC and that TNF-alpha and H2O2 induce apoptosis
      in hBMSC through the activation of JNK and NF-kappaB. Our findings also suggest
      that alpha-LA may have therapeutic applications in halting or attenuating bone
      loss associated with increased oxidative stress.

PMID- 15940366
TI  - Fibroblasts express RANKL and support osteoclastogenesis in a COX-2-dependent
      manner after stimulation with titanium particles.
AB  - Synovial fibroblasts are possible mediators of osteolysis. Fibroblasts respond
      directly to titanium particles and increase RANKL expression through a COX
      2/PGE2/EP4/PKA signaling pathway. Fibroblasts pretreated with titanium or PGE2
      stimulated osteoclast formation, showing the functional importance of RANKL
      induction. Synovial fibroblasts and their activation pathways are potential
      targets to prevent osteolysis. INTRODUCTION: Bone loss adjacent to the implant is
      a major cause of joint arthroplasty failure. Although the cellular and molecular
      response to microscopic wear debris particles is recognized as causative, little
      is known concerning role of synovial fibroblasts in these events. MATERIALS AND
      METHODS: Murine embryonic fibroblasts and knee synovial fibroblasts in culture
      stimulated with titanium particles were examined by FACS, real time RT-PCR,
      Northern blot, and Western blot for expressions of vascular cell adhesion
      molecule (VCAM)1, RANKL, cyclooxygenase (COX)-1, and COX-2, and the four
      prostaglandin E2 (PGE2) receptor isoforms. Experiments were performed in the
      presence and absence of COX inhibitors, protein kinase A (PKA) and protein kinase
      C (PKC) inhibitors, and various EP receptor agonists. Osteoclast formation was
      examined in co-cultures of pretreated glutaraldehyde-fixed fibroblasts and
      primary murine spleen cells treated with macrophage-colony stimulating factor (M
      CSF) for 7-days. RESULTS: TNF-alpha stimulated VCAM1 expression, consistent with
      a synovial fibroblast phenotype. Titanium particles stimulated RANKL gene and
      protein expressions in fibroblasts in a dose-dependent manner. Gene expression
      was increased 5-fold by 4 h, and protein levels reached a maximum after 48 h.
      Within 1 h, titanium particles also induced COX-2 mRNA and protein levels,
      whereas both indomethacin and celecoxib blocked the stimulation of RANKL,
      suggesting a COX-2-mediated event. Furthermore, PGE2 induced RANKL gene and
      protein expression and rescued RANKL expression in titanium-treated cultures
      containing COX-2 inhibitors. Fibroblast cultures pretreated with either PGE2 or
      titanium particles enhanced osteoclast formation, indicating the functional
      importance of RANKL induction. EP4 was the most abundant PGE2 receptor isoform,
      EP1 and EP2 were expressed at low levels, and EP3 was absent. The EP1 selective
      agonist iloprost and the EP2 selective agonist butaprost minimally stimulated
      RANKL. In contrast, the EP2 and EP4 agonist misoprostol induced RANKL to a
      magnitude similar to PGE2. Finally, PKA antagonism strongly repressed RANKL
      stimulation by PGE2. CONCLUSION: Fibroblasts respond directly to titanium
      particles and increase RANKL expression through a COX-2/PGE2/EP4/PKA signaling
      pathway. Thus, the synovial fibroblast is important mediator of osteolysis and
      target for therapeutic strategies.

PMID- 15940367
TI  - Overexpression of human PHEX under the human beta-actin promoter does not fully
      rescue the Hyp mouse phenotype.
AB  - XLH in humans and the Hyp phenotype in mice are caused by inactivating Phex
      mutations. Overexpression of human PHEX under the human beta-actin promoter in
      Hyp mice rescued the bone phenotype almost completely, but did not affect
      phosphate homeostasis, suggesting that different, possibly independent,
      pathophysiological mechanisms contribute to hyperphosphaturia and bone
      abnormalities in XLH. INTRODUCTION: Mutations in PHEX, a phosphate-regulating
      gene with homologies to endopeptidases on the X chromosome, are responsible for X
      linked hypophosphatemia (XLH) in humans, and its mouse homologs, Hyp, Phex(Hyp
      2J), Phex(Hyp-Duk), Gy, and Ska1. PHEX is thought to inactivate a phosphaturic
      factor, which may be fibroblast growth factor 23 (FGF)-23. Consistent with this
      hypothesis, FGF-23 levels were shown to be elevated in most patients with XLH and
      in Hyp mice. The aim of this study was, therefore, to examine whether transgenic
      overexpression of PHEX under the human beta-actin promoter would rescue the Hyp
      phenotype. MATERIALS AND METHODS: We tested this hypothesis by generating two
      mouse lines expressing human PHEX under the control of a human beta-actin
      promoter (PHEX-tg). With the exception of brain, RT-PCR analyses showed transgene
      expression in all tissues examined. PHEX protein, however, was only detected in
      bone, muscle, lung, skin, and heart. To assess the role of the mutant PHEX, we
      crossed female heterozygous Hyp mice with male heterozygous PHEX-tg mice to
      obtain wildtype (WT), PHEX-tg, Hyp, and Hyp/PHEX-tg offspring, which were
      examined at 3 months of age. RESULTS: PHEX-tg mice exhibited normal bone and
      mineral ion homeostasis. Hyp mice showed the known phenotype with reduced body
      weight, hypophosphatemia, hyperphosphaturia, and rickets. Hyp/PHEX-tg mice had
      almost normal body weight relative to WT controls, showed a dramatic improvement
      in femoral BMD, almost normal growth plate width, and, despite remaining
      disturbances in bone mineralization, almost normal bone architecture and
      pronounced improvements of osteoidosis and of halo formation compared with Hyp
      mice. However, Hyp and Hyp/PHEX-tg mice had comparable reductions in tubular
      reabsorption of phosphate and were hypophosphatemic relative to WT controls.
      CONCLUSION: Our data suggest that different, possibly independent,
      pathophysiological mechanisms contribute to renal phosphate wasting and bone
      abnormalities in Hyp and XLH.

PMID- 15940368
TI  - Annexin II stimulates RANKL expression through MAPK.
AB  - We report that AX-II, in addition to inducing GM-CSF expression, also increases
      membrane-bound RANKL synthesis by marrow stromal cells and does so through a
      previously unreported MAPK-dependent pathway. Thus, both GM-CSF and RANKL are
      required for AX-II stimulation of OCL formation. INTRODUCTION: Annexin II (AX-II)
      is an autocrine/paracrine factor secreted by osteoclasts (OCLs) that stimulates
      human OCL formation and bone resorption in vitro by inducing bone marrow stromal
      cells and activated CD4+ T cells to produce granulocyte-macrophage colony
      stimulating factor (GM-CSF). GM-CSF in turn increases OCL precursor proliferation
      and further enhances OCL formation. However, the induction of GM-CSF by AX-II
      cannot fully explain its effects on OCL formation. In this study, we tested the
      capacity of AX-II to induce the expression of RANKL and the corresponding
      signaling pathways AX-II employs in human marrow stromal cells to induce RANKL.
      We also showed that both GM-CSF and RANKL are required for OCL formation induced
      by AX-II. MATERIALS AND METHODS: Real-time RT-PCR and Western blot analysis were
      used to detect RANKL and osteoprotegerin (OPG) mRNA and protein expression in
      unfractionated human bone marrow mononuclear cells stimulated with AX-II. Soluble
      RANKL in the conditioned medium was analyzed by ELISA. Activation of the MAPK
      pathway by AX-II was tested by Western blot. The effects of OPG and anti-GM-CSF
      on AX-II-induced OCL formation were also examined. RESULTS AND CONCLUSION: In
      addition to upregulating GM-CSF mRNA, AX-II increased RANKL mRNA expression dose
      dependently in unfractionated human bone marrow mononuclear cells and modestly
      increased soluble RANKL in unfractionated human bone marrow mononuclear cell
      conditioned medium. However, AX-II markedly increased membrane-bound RANKL on
      human bone marrow stromal cells. Treatment of marrow stromal cells with AX-II
      activated MAP-kinase (ERKs) and PD 98059 abolished the effect but did not block
      the increase in GM-CSF. Interestingly, OPG, a natural decoy receptor for RANKL,
      or anti-GM-CSF partially inhibited OCL formation by AX-II in human bone marrow
      cells, and the combination of OPG and anti-GM-CSF completely blocked AX-II
      induced OCL formation. These data show that AX-II stimulates both the
      proliferation and differentiation of OCL precursors through production of GM-CSF
      and RANKL respectively.

PMID- 15940369
TI  - Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis,
      misregulates cell surface expression and trafficking of BMPRIA.
AB  - FOP is a disorder in which skeletal muscle is progressively replaced with bone.
      FOP lymphocytes, a model system for exploring the BMP pathway in these patients,
      exhibit a defect in BMPRIA internalization and increased activation of downstream
      signaling, suggesting that altered BMP receptor trafficking underlies ectopic
      bone formation in this disease. INTRODUCTION: Fibrodysplasia ossificans
      progressiva (FOP) is a severely disabling disorder characterized by progressive
      heterotopic ossification of connective tissues. Whereas the genetic defect and
      pathophysiology of this condition remain enigmatic, BMP4 mRNA and protein are
      overexpressed, and mRNAs for a subset of secreted BMP antagonists are not
      synthesized at appropriate levels in cultured lymphocytes from FOP patients.
      These data suggest involvement of altered BMP signaling in the disease. In this
      study, we investigate whether the abnormality is associated with defective BMP
      receptor function in lymphocytes. MATERIALS AND METHODS: Cell surface proteins
      were quantified by fluorescence-activated cell sorting (FACS). Protein
      phosphorylation was assayed by immunoprecipitation and immunoblotting. Protein
      synthesis and degradation were examined by [35S]methionine labeling and pulse
      chase assays. mRNA was detected by RT-PCR. RESULTS: FOP lymphocytes expressed 6
      fold higher levels of BMP receptor type IA (BMPRIA) on the cell surface compared
      with control cells and displayed a marked reduction in ligand-stimulated
      internalization and degradation of BMPRIA. Moreover, in control cells, BMP4
      treatment increased BMPRIA phosphorylation, whereas BMPRIA showed ligand
      insensitive constitutive phosphorylation in FOP cells. Our data additionally
      support that the p38 mitogen-activated protein kinase (MAPK) signaling pathway is
      a major BMP signaling pathway in these cell lines and that expression of
      inhibitor of DNA binding and differentiation 1 (ID-1), a transcriptional target
      of BMP signaling, is enhanced in FOP cells. CONCLUSIONS: These data extend our
      previous observations of misregulated BMP4 signaling in FOP lymphocytes and show
      that cell surface overabundance and constitutive phosphorylation of BMPRIA are
      associated with a defect in receptor internalization. Altered BMP receptor
      trafficking may play a significant role in FOP pathogenesis.

PMID- 15940370
TI  - Comparison insight bone measurements by histomorphometry and microCT.
AB  - Morphometric analysis of 70 bone biopsies was done in parallel by microCT and
      histomorphometry. microCT provided higher results for trabecular thickness and
      separation because of the 3D shape of these anatomical objects. INTRODUCTION:
      Bone histomorphometry is used to explore the various metabolic bone diseases. The
      technique is done on microscopic 2D sections, and several methods have been
      proposed to extrapolate 2D measurements to the 3D dimension. X-ray microCT is a
      recently developed imaging tool to appreciate 3D architecture. Recently the use
      of 2D histomorphometric measurements have been shown to provide discordant
      results compared with 3D values obtained directly. MATERIAL AND METHODS: Seventy
      human bone biopsies were removed from patients presenting with metabolic bone
      diseases. Complete bone biopsies were examined by microCT. Bone volume (BV/TV),
      Tb.Th, and Tb.Sp were measured on the 3D models. Tb.Th and Tb.Sp were measured by
      a method based on the sphere algorithm. In addition, six images were resliced and
      transferred to an image analyzer: bone volume and trabecular characteristics were
      measured after thresholding of the images. Bone cores were embedded
      undecalcified; histological sections were prepared and measured by routine
      histomorphometric methods providing another set of values for bone volume and
      trabecular characteristics. Comparison between the different methods was done by
      using regression analysis, Bland-Altman, Passing-Bablock, and Mountain plots.
      RESULTS: Correlations between all parameters were highly significant, but microCT
      overestimated bone volume. The osteoid volume had no influence in this series.
      Overestimation may have been caused by a double threshold used in microCT, giving
      trabecular boundaries less well defined than on histological sections.
      Correlations between Tb.Th and Tb.Sp values obtained by 3D or 2D measurements
      were lower, and 3D analysis always overestimated thickness by approximately 50%.
      These increases could be attributed to the 3D shape of the object because the
      number of nodes and the size of the marrow cavities were correlated with 3D
      values. CONCLUSION: In clinical practice, microCT seems to be an interesting
      method providing reliable morphometric results in less time than conventional
      histomorphometry. The correlation coefficient is not sufficient to study the
      agreement between techniques in histomorphometry. The architectural descriptors
      are influenced by the algorithms used in 3D.

PMID- 15940371
TI  - Predictive value of BMD for hip and other fractures.
AB  - The relationship between BMD and fracture risk was estimated in a meta-analysis
      of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD
      was an important predictor of fracture risk. The prediction of hip fracture with
      hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was
      to quantify the relationship between BMD and fracture risk and examine the effect
      of age, sex, time since measurement, and initial BMD value. MATERIALS AND
      METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising
      EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES,
      Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3
      years and a total of 168,366 person-years. The effect of BMD on fracture risk was
      examined using a Poisson model in each cohort and each sex separately. Results of
      the different studies were then merged using weighted coefficients. RESULTS: BMD
      measurement at the femoral neck with DXA was a strong predictor of hip fractures
      both in men and women with a similar predictive ability. At the age of 65 years,
      risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI =
      2.31-3.59) in women for each SD decrease in BMD. However, the effect was
      dependent on age, with a significantly higher gradient of risk at age 50 years
      than at age 80 years. Although the gradient of hip fracture risk decreased with
      age, the absolute risk still rose markedly with age. For any fracture and for any
      osteoporotic fracture, the gradient of risk was lower than for hip fractures. At
      the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41
      per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI =
      1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased
      with age. For the prediction of any osteoporotic fracture (and any fracture),
      there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the
      risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the
      risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar
      but less pronounced and nonsignificant effect was observed for hip fractures.
      Data for ultrasound and peripheral measurements were available from three
      cohorts. The predictive ability of these devices was somewhat less than that of
      DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We
      conclude that BMD is a risk factor for fracture of substantial importance and is
      similar in both sexes. Its validation on an international basis permits its use
      in case finding strategies. Its use should, however, take account of the
      variations in predictive value with age and BMD.

PMID- 15940372
TI  - Femoral neck bone loss predicts fracture risk independent of baseline BMD.
AB  - Whereas low BMD is known to be a risk factor for fracture, it is not clear
      whether loss of BMD is also a risk factor. In elderly women, greater loss of BMD
      at the femoral neck was associated with increased risk of fracture, independent
      of baseline BMD and age. INTRODUCTION: Baseline measurement of BMD predicts
      fracture risk. However, it is not clear whether short-term bone loss is an
      independent risk factor for fractures. This study was designed to investigate the
      relationship between changes in BMD and fracture risk in elderly women in the
      general population. MATERIALS AND METHODS: A total of 966 women > or = 60 years
      of age (mean, 70 +/- 6.7 [SD] years), who had been followed for an average of
      10.7 years, were studied. Atraumatic fracture of the proximal femur (hip),
      symptomatic vertebral fracture, and other major fractures, excluding pathological
      fractures or those resulting from severe trauma, were recorded and confirmed by
      radiographs. Femoral neck and lumbar spine BMD was measured by DXA. RESULTS:
      During the follow-up period, 224 had sustained a fracture (including 43 hip, 71
      symptomatic vertebrae, 37 proximal humerus, 46 forearm and wrist, and 27 rib and
      pelvis fractures). The annual rate of change in BMD in fracture women (-2.1 +/-
      4.2%) was significantly higher than that in nonfracture women (-0.8 +/- 2.8%; p =
      0.005). In the multivariable Cox's proportional hazards analysis, the following
      factors were significant predictors of fracture risk: femoral neck bone loss
      (relative hazard [RH], 1.4; 95% CI, 1.1-1.8 per 5% loss), baseline femoral neck
      BMD (RH, 2.0; 95% CI, 1.7-2.7 per SD), and advancing age (RH, 1.2; 95% CI, 1.1
      1.4). The proportion of fractures attributable to the three factors was 45%. For
      hip fracture, the attributable risk fraction was approximately 90%. CONCLUSION:
      Bone loss at the femoral neck is a predictor of fracture risk in elderly women,
      independent of baseline BMD and age.

PMID- 15940373
TI  - Examining bone surfaces across puberty: a 20-month pQCT trial.
AB  - This follow-up study assessed sex differences in cortical bone growth at the
      tibial midshaft across puberty. In both sexes, periosteal apposition dominated
      over endosteal resorption. Boys had a greater magnitude of change at both
      surfaces, and thus, a greater increase in bone size across puberty. Relative
      increase in cortical bone area was similar between sexes. INTRODUCTION:
      Generally, sex differences in bone size become most evident as puberty
      progresses. This was thought to be caused, in part, by greater periosteal
      apposition in boys, whereas endosteal apposition prevailed in girls. However,
      this premise is based on evidence from cross-sectional studies and planar
      measurement techniques. Thus, our aim was to prospectively evaluate sex-specific
      changes in cortical bone area across puberty. MATERIALS AND METHODS: We used pQCT
      to assess the tibial midshaft (50% site) at baseline and final (20 months) in
      girls (N = 68) and boys (N = 60) across early-, peri-, and postpuberty. We report
      total bone cross-sectional area (ToA, mm2), cortical area (CoA, mm2), marrow
      cavity area (CavA, mm2), and CoA/ToA ratio. RESULTS: Children were a mean age of
      11.9 +/- 0.6 (SD) years at baseline. At the tibia, CoA ranged from 230 +/- 44,
      261 +/- 50, and 258 +/- 46 in early-, peri-, and postpubertal girls. In boys,
      comparable values were 223 +/- 36 (early), 264 +/- 38 (peri), and 281 +/- 77
      (postpubertal). There was no sex difference for ToA or CoA at baseline. Increase
      in ToA and CoA was, on average, 10% greater for boys than girls across maturity
      groups. The area of the marrow cavity increased in all groups, but with
      considerable variability. The increase in CavA was significantly less for girls
      than boys in the early- and postpubertal groups. Change in CoA/ToA was similar
      between sexes across puberty. CONCLUSION: Both sexes showed a similar pattern of
      change in CoA at the tibial midshaft, where periosteal apposition dominated over
      endosteal resorption. Boys showed a greater magnitude of change at both surfaces,
      and thus, showed a greater increase in bone size across puberty. The relative
      increase in cortical area was similar between sexes. These pQCT findings provide
      no evidence for endosteal apposition in postmenarchal girls.

PMID- 15940374
TI  - Smoking and the risk of fracture in older men.
AB  - The role of smoking on fracture risk in older men was studied within a
      longitudinal population-based cohort study. Using time-dependent exposure
      information and analysis, smoking was detected to be a stronger, dose-dependent
      and a more long lasting risk factor for fracture than has previously been
      estimated. INTRODUCTION: Although several studies have indicated a negative
      influence of smoking on fracture risk in women, there are few studies in men. No
      study in either sex has considered that smoking exposure may vary during follow
      up in a cohort study. There is a need for a prospective study with repeated
      measures to analyze smoking exposure and fracture risk in men. MATERIALS AND
      METHODS: A total of 2322 men, 49-51 years of age, were enrolled in a
      longitudinal, population-based cohort study. Smoking status and other lifestyle
      habits were established at baseline and additionally at 60, 70, and 77 years of
      age. One or more fractures were documented in 272 men during 30 years of follow
      up. Cox proportional hazards regression was used to determine the rate ratio (RR)
      of fracture according to time-dependent smoking habits and covariates. RESULTS:
      The overall adjusted fracture risk was increased in current (RR, 2.71; 95% CI,
      1.86-3.95) and former smokers (RR, 1.66, 95% CI; 1.18-2.34), and persistent until
      30 years after cessation. Among current smokers, the adjusted risk of any
      fracture increased by 30% (95% CI, 6-58%) for every 5 g of tobacco smoked each
      day. Smoking duration did not substantially influence fracture risk in either
      current or former smokers. One-half (52%; 95% CI, 35-65%) of all fractures were
      attributable to current smoking. CONCLUSIONS: Tobacco smoking seems to be a long
      lasting major risk factor for fracture in older men, and the risks depends both
      on recency of smoking and on the daily amount of tobacco smoked, rather than
      smoking duration.

PMID- 15940376
TI  - Age of attainment of peak bone mass is site specific in Swedish men--The GOOD
      study.
AB  - Results from this study suggest that PBM has been attained in the spine and
      femoral neck, but not in the radius or tibia, in 18- to 20-year-old men, in which
      an endosteal contraction and increase in cortical volumetric BMD is observed.
      INTRODUCTION: Peak bone mass (PBM) is an important determinant for the risk of
      osteoporosis. In men, the age of attainment of PBM has been under some
      controversy. The objective of this study was to determine if peak bone mass had
      been attained, and whether it is site specific, in 18- to 20-year-old Swedish
      men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants
      (GOOD) Study consists of 1068 men, 18.9 +/- 0.6 years of age. BMD was measured
      using both DXA and pQCT. Environmental factors, such as dietary intake and
      physical activity, were assessed through questionnaires. The independent
      predictors of BMD were assessed through multiple linear regression, including
      age, height, weight, calcium intake, smoking, and physical activity. RESULTS AND
      CONCLUSIONS: We show, in a large well-characterized cohort, that age was not an
      independent predictor of BMD of the lumbar spine, femoral neck, or total body,
      indicating that peak BMD has been achieved in these skeletal sites, whereas it
      was an independent predictor of BMD of the radius, suggesting that peak BMD has
      not yet been attained in the long bones. pQCT analyses of the radius and the
      tibia revealed that age was associated with cortical volumetric BMD and endosteal
      contraction of the radius and tibia. These results show that the age of
      attainment of PBM is site specific.

PMID- 15940375
TI  - What proportion of incident radiographic vertebral deformities is clinically
      diagnosed and vice versa?
AB  - We prospectively examined, in a large cohort of older women, the proportion of
      incident radiographic vertebral deformities diagnosed as incident clinical
      vertebral fractures in the same women at the same vertebral level. The proportion
      of deformities clinically diagnosed ranged from <15% for milder deformities to
      nearly 30% for more severe deformities. INTRODUCTION: The relationship between
      radiographic and clinical vertebral fractures is incompletely understood. No
      previous study has prospectively compared the agreement between incident
      radiographic vertebral deformities and incident community-recognized,
      radiographically confirmed vertebral fractures in the same women at the same
      vertebral level(s). MATERIALS AND METHODS: This analysis of data from the
      Fracture Intervention Trial included all participants who completed both baseline
      and at least one scheduled follow-up lateral spinal radiograph (n = 6084).
      Incident vertebral deformities were defined at a given vertebral level as a
      reduction between baseline and closeout radiographs of > or = 20% and 4 mm in any
      vertebral height and subdivided into two severity categories. Incident clinical
      vertebral fractures were those reported to clinical centers by participants and
      confirmed by the study radiologist, who compared the community spinal radiograph
      with the participant's baseline study radiograph using semiquantitative methods.
      RESULTS: A total of 446 incident radiographic vertebral deformities were
      identified in 330 women, whereas 121 women experienced one or more confirmed
      incident clinical vertebral fracture. Of incident radiograpic vertebral
      deformities, 22.6% were also clinically diagnosed as incident vertebral
      fractures, with clinical diagnoses made for 28.4% of the deformities that
      exceeded 30% and 4 mm height loss (severe deformity) compared with 14.3% for
      deformities that involved > or = 20% and 4 mm but < 30% height loss (milder
      deformity). Of incident clinical vertebral fractures, 72.7% were morphometrically
      identified as incident deformities, most of them as severe deformities. More than
      20% of incident clinical fractures were not identified as incident deformities by
      even the most liberal morphometric criterion used in this study. CONCLUSIONS:
      Approximately one-fourth of incident radiographic vertebral deformities were
      clinically diagnosed as new vertebral fractures, although the proportion
      clinically diagnosed was increased for more severe deformities. Whereas most
      incident clinical vertebral fractures were identified as severe morphometric
      deformities, approximately one-fourth did not meet even the most liberal study
      criterion for morphometric deformity. Further study of factors that may explain
      the discordance between incident vertebral deformities and incident clinical
      vertebral fractures is important.

PMID- 15940377
TI  - Racial differences in rate of decline in bone mass in older men: the Baltimore
      men's osteoporosis study.
AB  - Older black men have higher adjusted BMD than older white men. Using data from a
      longitudinal cohort study of older men followed for a mean of 18.8 +/- 6.5 (SD)
      months, we found that older black men have a higher rate of decline in femoral
      neck and total hip BMD and femoral neck BMAD than older white men. INTRODUCTION:
      Older black men have higher adjusted BMD compared with older white men. The
      difference in BMD may be caused by having attained higher peak bone mass as young
      adults and/or having a slower rate of decline in bone mass as adults. There are
      few published longitudinal data on change in bone mass in older white men and no
      published data for older black men. MATERIALS AND METHODS: Three hundred forty
      nine white men and 119 black men 65 of age (mean age, 75 +/- 5.7 and 72 +/- 5.6
      years, respectively) who participated in the longitudinal component of the
      Baltimore Men's Osteoporosis Study returned for a second visit after a mean of
      18.8 +/- 6.5 (SD) months and were not taking medications used to treat low bone
      mass at either visit. BMD was measured at the femoral neck and total hip by
      Hologic-certified technicians using a QDR 2000 at the baseline visit (V1) and QDR
      4500 at the first follow-up visit (V2). Participants also completed self
      administered and interviewer-administered questionnaires and underwent
      standardized clinic examinations. Bone mineral apparent density (BMAD) at the
      femoral neck was calculated as an estimate of volumetric BMD. Annual crude and
      multiple variable adjusted percent changes in BMD and BMAD were calculated.
      RESULTS: In univariate analyses, black men had lower percent decline in femoral
      neck and total hip BMD and femoral neck BMAD than white men. In addition, older
      age at baseline, lower baseline weight, current smoking, and lower baseline BMD
      were associated with greater percent decline per year in femoral neck BMD; older
      age at baseline, current smoking, and lower baseline BMD were associated with
      greater percent decline per year in total hip BMD; and older age at baseline and
      lower baseline femoral neck BMAD were associated with greater percent decline per
      year in femoral neck BMAD. Racial differences in bone loss persisted in multiple
      variable models that controlled for other factors associated with change in BMD
      and BMAD. CONCLUSIONS: Older black men seem to lose bone mass at a slower rate
      than older white men. These differences in the rate of bone loss may account, in
      part, for the racial disparities in BMD and BMAD and risk of osteoporotic
      fractures among older men.

PMID- 15940378
TI  - Effects of intravenous pamidronate treatment in infants with osteogenesis
      imperfecta: clinical and histomorphometric outcome.
AB  - Clinical and histomorphometric outcome was compared between children with OI who
      had received pamidronate since infancy and age-matched patients who had never
      received pamidronate. Pamidronate was associated with improved vertebral shape
      and mass, higher cortical width, increased cancellous bone volume, and suppressed
      bone turnover. INTRODUCTION: Observations in small patient series indicate that
      infants with severe osteogenesis imperfecta (OI) benefit from treatment with
      cyclical intravenous pamidronate. However, detailed analyses of outcome are
      lacking for this age group. MATERIALS AND METHODS: Clinical outcome was evaluated
      in 29 children with OI types I (n = 3), III (n = 14), or IV (n = 12) who started
      pamidronate therapy before 2 years of age (age at treatment onset: median, 6
      months; range, 2 weeks to 23 months) and who had completed 3 years of treatment
      (total annual pamidronate dose, 9 mg/kg). They were compared with a historical
      control group of 29 untreated children with severe OI who were matched for OI
      type and age at the 3-year treatment time-point. In addition, iliac bone
      histomorphometry was compared between 24 pamidronate-treated patients and 24 age
      matched OI patients who had not received pamidronate. RESULTS: Morphometric
      evaluation of lumbar vertebrae (L(1)-L(4)) showed that the shape of vertebral
      bodies was better preserved in pamidronate-treated patients. This was accompanied
      by significantly higher lumbar spine areal and volumetric BMD (+110 and +96%,
      respectively) and a larger vertebral bone volume (+26%) on densitometry.
      Regarding mobility function, the Pediatric Evaluation of Disability Inventory
      gross motor score was 50% greater in the pamidronate group (p < 0.001). Iliac
      bone histomorphometry showed 61% higher cortical width and 89% higher cancellous
      bone volume in pamidronate-treated patients. Bone formation rate per bone surface
      in the pamidronate group was only 17% that of untreated patients. CONCLUSIONS: In
      conclusion, this study suggests that cyclical pamidronate treatment started in
      infancy leads to improved bone strength and better gross motor function but also
      suppresses bone turnover markedly. It is therefore prudent to reserve pamidronate
      treatment to infant OI patients who present with a moderate to severe phenotype.

PMID- 15940379
TI  - Differential effects of teriparatide and alendronate on bone remodeling in
      postmenopausal women assessed by histomorphometric parameters.
AB  - An 18-month randomized double-blind study was conducted in postmenopausal women
      with osteoporosis to compare the effects of once-daily teriparatide 20 microg
      with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42
      patients. Indices of bone formation were significantly higher after 6 or 18
      months of teriparatide compared with alendronate treatment. INTRODUCTION:
      Alendronate and teriparatide increased BMD, assessed by DXA, by different
      mechanisms of action, supported by changes in biochemical markers of bone
      turnover. The purpose of this cross-sectional study was to explore the
      differential effects of these two osteoporosis treatments at the bone tissue
      level by examining bone histomorphometric parameters of bone turnover after
      either 6 or 18 months of treatment. MATERIALS AND METHODS: Patients were a cohort
      from a randomized parallel double-blind study conducted to compare the effects of
      once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women
      with osteoporosis. Transiliac crest bone biopsies were obtained after
      tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18
      months (n = 14); 5 additional patients were biopsied from contralateral sides at
      6 and 18 months. Biopsy specimens adequate for quantitative analysis were
      analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n =
      8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8;
      alendronate, n = 7). Data were analyzed by two-sample tests. RESULTS:
      Histomorphometric indices of bone formation were significantly and markedly
      greater in the teriparatide group than in the alendronate group at 6 and 18
      months, whereas indices of bone resorption were only significantly greater in the
      teriparatide group than in the alendronate group at 6 months. Bone formation and
      activation frequency were significantly lower at 18 months compared with 6 months
      in the teriparatide group, returning to levels comparable with untreated
      postmenopausal women. In the teriparatide group, the peak in histomorphometric
      bone formation indices coincided with peak levels for N-terminal propeptide of
      type I collagen, a biochemical marker of bone formation. The degree of
      mineralization was lower at 18 months than at 6 months with treatment in both
      groups but was not different between groups. CONCLUSIONS: These results confirm
      the opposite mechanisms of action of teriparatide and alendronate on bone
      remodeling and confirm the bone formation effect of teriparatide.

PMID- 15940380
TI  - An autosomal dominant high bone mass phenotype in association with
      craniosynostosis in an extended family is caused by an LRP5 missense mutation.
AB  - Gain-of-function mutations in LRP5 have been shown to cause high BMD disorders
      showing variable expression of some clinical symptoms, including torus palatinus
      and neurological complications. In an extended family, we were able to add
      craniosynostosis and developmental delay to the clinical spectrum associated with
      LRP5 mutations. We report on an extended four-generation family with 13 affected
      individuals (7 men and 6 women) in which an autosomal dominant type of
      osteosclerosis segregates. Osteosclerosis was most pronounced in the cranial base
      and calvarium, starting in early childhood with variable expression and a
      progressive character. Craniosynostosis at an early age was reported in four
      affected family members (two males and two females). The patients also presented
      with dysmorphic features (macrocephaly, brachycephaly, wide and high forehead,
      hypertelorism, prominent cheekbones, prominent jaw). They have normal height and
      proportions. Neurological complications like entrapment of cranial nerves
      resulting in optical nerve atrophy, hearing loss, and facial palsy were reported
      in two individuals. A mild developmental delay was reported in three affected
      individuals. None of the patients have torus palatinus, increased rate of
      fractures, osteomyelitis, hepatosplenomegaly, or pancytopenia. A missense
      mutation 640G-->A (A214T) in the low-density lipoprotein receptor-related protein
      5 (LRP5) gene was found in all affected individuals analyzed, including cases in
      whom craniosynostosis, a mild developmental delay, and/or macrocephaly is
      observed. To our knowledge, this is the first report in the literature of
      patients presenting with autosomal dominant osteosclerosis in whom a variable
      expression of craniosynostosis, macrocephaly, and mild developmental delay is
      observed, which is most likely associated with a mutation in the LRP5 gene. These
      phenotypes can therefore be added to the clinical spectrum of LRP5-associated
      bone disorders.

PMID- 15940381
TI  - How to interpret surrogate markers of efficacy in osteoporosis.

PMID- 15940383
TI  - No evidence of insulin resistance in normal weight vegetarians. A case control
      study.
AB  - BACKGROUND: Diets rich in carbohydrates with a low glycemic index and with high
      fiber content are associated with flat post-prandial rises of blood glucose,
      minimal post-prandial insulin secretion and maintenance of insulin sensitivity.
      Protective food commodities in the prevention of cardiovascular disease, insulin
      resistance syndrome or diabetes are crucial components of the vegetarian diet.
      AIM OF THE STUDY: Insulin resistance values were assessed in relation to
      different nutrition. Metabolic abnormality is a predictor of age-related diseases
      and can be more pronounced in obese subjects. Insulin resistance values in normal
      weight subjects of two different nutritional habits were correlated with age.
      METHODS: Fasting concentrations of glucose and insulin as well as calculated
      values of insulin resistance IR (HOMA) were assessed in two nutritional groups of
      apparently healthy adult subjects (age range 19 - 64 years) with normal weight
      (body mass index 18.6 - 25.0 kg/m(2)): a vegetarian group (95 long-term lacto-ovo
      vegetarians; duration of vegetarianism 10.2 +/- 0.5 years) and a non-vegetarian
      control group (107 subjects of general population on traditional western diet).
      Intake of energy and main nutrients (fats, saccharides, proteins) was similar in
      both groups. RESULTS: Glucose and insulin concentrations and IR (HOMA) values
      were significantly lower in vegetarians (glucose 4.47 +/- 0.05 vs. 4.71 +/- 0.07
      mmol/l; insulin 4.96 +/- 0.23 vs. 7.32 +/- 0.41 mU/l; IR (HOMA) 0.99 +/- 0.05 vs.
      1.59 +/- 0.10). IR (HOMA) dependence on age was only significant in subjects on a
      western diet. A significant increase of IR was found already in the age range 31
      40 years, compared to vegetarians and it continued in later age decades. Age
      independent and low insulin resistance values in vegetarians are a consequence of
      an effective diet prevention by long-term frequent consumption of protective
      food. Vegetarians had a significantly higher consumption of whole grain products,
      pulses, products from oat and barley. CONCLUSION: The results of age independent
      and low values of insulin resistance document a beneficial effect of long-term
      vegetarian nutrition in prevention of metabolic syndrome, diabetes and
      cardiovascular disease.

PMID- 15940384
TI  - Familial frontotemporal dementia associated with the novel MAPT mutation T427M.

PMID- 15940385
TI  - Blood transfusion-induced irreversible brain damage.

PMID- 15940387
TI  - Chronic inflammatory demyelinating polyneuropathy and respiratory failure.
AB  - Neuromuscular respiratory failure is not considered to be a clinical feature of
      chronic inflammatory demyelinating polyneuropathy (CIDP). We present 4 patients
      with CIDP who required respiratory assistance and mechanical ventilation. Two
      patients needed emergent intubation and one patient lapsed in a stupor from
      hypercapnia. Respiratory failure in CIDP should be considered exceptional, but
      more formal studies in CIDP may be needed to assess its prevalence.

PMID- 15940386
TI  - The combination of cyclophosphamide plus interferon beta as rescue therapy could
      be used to treat relapsing-remitting multiple sclerosis patients-- twenty-four
      months follow-up.
AB  - The aim of the present study was to evaluate the efficacy of the combination of
      cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing
      remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure
      during IFN beta therapy. It is the general experience that immunomodulatory
      agents (IMA) are only partially effective in RR patients. Recent data on the
      efficacy of immunosuppressive therapies for these patients are encouraging. The
      anti-inflammatory and immunosuppressive effects of CTX have been utilized to
      treat selected cases of multiple sclerosis with a progressive and worsening
      course as rescue therapy. Thirty RR MS patients with clinically defined MS who
      experienced treatment failure during IFN beta therapy (2 or more relapses per
      year or 1.5 EDSS point worsening in one year) were enrolled in the study and
      treated with CTX iv pulse therapy added to IFN beta and followed up for 24
      months. As primary endpoints we evaluated the yearly relapse rate. We also
      evaluated the percentage of patients free of relapses and of EDSS variations. We
      analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and
      24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30
      RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed
      a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further
      improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of
      relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to
      2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation
      of MRI lesion load and no severe adverse events were recorded during the study.
      These data showed that the combination of CTX plus IFN beta halted the
      progression of disease in active and deteriorating MS patients suggesting the
      necessity of RCTs to test the efficacy of this combination therapy in active RRMS
      patients or in patients who experienced treatment failure in response to disease
      modifying drugs (DMDs).

PMID- 15940388
TI  - Association of the endothelial nitric oxide synthase (NOS3) Glu298Asp gene
      polymorphism with the risk of Alzheimer's disease-- a meta-analysis.

PMID- 15940389
TI  - Different clinical and evolutional patterns in late idiopathic and vascular
      parkinsonism.
AB  - OBJECTIVE: The aim of this study was to examine the clinical picture of
      Parkinson's disease (PD) and vascular parkinsonism (VP) in the elderly, in an
      attempt to differentiate the clinical history, symptoms, signs and response to
      therapy. MATERIAL AND METHODS: Thirty-two elderly patients with late onset PD and
      45 with VP were enrolled and the clinical features of two groups were compared.
      All patients underwent brain MRI and were scored using the Unified Parkinson's
      Disease Rating Scales (UPDRS) -II, -III. RESULTS: Patients with PD had a younger
      age at onset and a longer duration of the disease as compared to patients with
      VP. Nearly all PD patients showed a good response to levodopa therapy, while only
      29% of patients with VP were responsive to levodopa treatment. Vascular risk
      factors as well as postural tremor, gait disorders and pyramidal signs with lower
      body predominance, were more frequent in patients with VP. Ninety-three % of PD
      patients had normal MRI, whereas all patients with VP had cerebral vascular
      lesions. UPDRS-II, -III scores at baseline were higher in VP than in PD patients
      and their increases throughout the follow-up period were more marked in VP than
      in PD patients. CONCLUSIONS: Clinical history, symptoms, signs, response to
      therapy, and brain imaging help to differentiate PD and VP as two clinical
      entities with different clinical, prognostic and therapeutic implications, even
      if the coexistence of PD and a cerebral vascular disease in elderly patients is
      not infrequent and can make the diagnosis difficult.

PMID- 15940390
TI  - Fifty-year perspective of "cystic fibrosis of the pancreas".

PMID- 15940391
TI  - Stage-I osteochondritis dissecans versus normal variants of ossification in the
      knee in children.
AB  - BACKGROUND: Juvenile osteochondritis dissecans (OCD) has a better prognosis than
      the adult type. OBJECTIVE: We postulated that the excellent prognosis of juvenile
      OCD could be explained, at least in part, by the erroneous diagnosis of some
      developmental variants of ossification as stage-I OCD. MATERIALS AND METHODS:
      Knee MRIs of 38 children, ages 7.5-17.7 years (mean and median age 13 years),
      were retrospectively reviewed to look for features that might separate normal
      variants of ossification from stage-I OCD. These included age, gender, site,
      configuration of the lesion, residual cartilaginous model and presence of edema.
      RESULTS: Twenty-three patients (32 condyles) had ossification defects with intact
      articular cartilage suggestive of stage-I lesions. No stage-II lesions were seen
      in the posterior femoral condyles. Accessory ossification centers were seen in
      11/16 posterior condyles and 3/16 central condyles. Spiculation of existing
      ossification was seen in 12/16 posterior condylar lesions and 1/16 central
      condyles. There was a predominance of accessory ossifications and spiculations in
      the patients with 10% or greater residual cartilaginous model. No edema signal
      greater than diaphyseal red-marrow signal was seen in the posterior condyles.
      Clinical follow-up ranged from 0.5 to 38 months, with clinical improvement in 22
      out of 23 patients. CONCLUSION: Inclusion of normal variants in the stage-I OCD
      category might explain, in part, the marked difference in published outcome
      between the juvenile and adult forms of OCD. Ossification defects in the
      posterior femoral condyles with intact overlying articular cartilage, accessory
      ossification centers, spiculation, residual cartilaginous model, and lack of bone
      marrow edema are features of developmental variants rather than OCD.

PMID- 15940392
TI  - Juvenile intraosseous gout of the calcaneus.
AB  - Gout presenting as an osteolytic lesion is exceedingly rare in children with
      asymptomatic hyperuricemia. We report the clinical and radiological presentation
      of intraosseous gout in a 13-year-old boy.

PMID- 15940393
TI  - Genetic variations in the gene encoding TFAP2B are associated with type 2
      diabetes mellitus.
AB  - To search a gene(s) conferring susceptibility to type 2 diabetes mellitus, we
      genotyped nearly 60,000 gene-based SNPs for Japanese patients and found evidence
      that the gene at chromosome 6p12 encoding transcription-factor-activating protein
      2beta (TFAP2B) was a likely candidate in view of significant association of
      polymorphism in this gene with type 2 diabetes. Extensive analysis of this region
      identified that several variations within TFAP2B were significantly associated
      with type 2 diabetes [a variable number of tandem repeat locus: chi(2)=10.9,
      P=0.0009; odds ratio=1.57, 95% CI 1.20-2.06, intron 1+774 (G/T); chi(2)=11.6,
      P=0.0006; odds ratio=1.60, 95% CI 1.22-2.09, intron 1+2093 (A/C); chi(2)=12.2,
      P=0.0004; odds ratio=1.61, 95% CI 1.23-2.11]. The association of TFAP2B with type
      2 diabetes was also observed in the UK population. These results suggest that
      TFAP2B might be a new candidate for conferring susceptibility to type 2 diabetes
      and contribute to the pathogenesis of type 2 diabetes.

PMID- 15940394
TI  - Analysis of expressed sequence tags in prothallia of Adiantum capillus-veneris.
AB  - The analysis of expressed sequences from a diverse set of plant species has
      fueled the increase in understanding of the complex molecular mechanisms
      underlying plant growth regulation. While representative data sets can be found
      for the major branches of plant evolution, fern species data are lacking. To
      further the availability of genetic information in pteridophytes, a normalized
      cDNA library of Adiantum capillus-veneris was constructed from prothallia grown
      under white light. A total of 10,420 expressed sequence tags (ESTs) were obtained
      and clustering of these sequences resulted in 7,100 nonredundant clusters. Of
      these, 1,608 EST clusters were found to be similar to sequences of known function
      and 1,092 EST clusters showed similarity to sequences of unknown function. Given
      the usefulness of Adiantum for developmental studies, the sequence data
      represented in this report stand to make a significant contribution to the
      understanding of plant growth regulation, particularly for pteridophytes.

PMID- 15940395
TI  - Bone mineral density and fracture risk in type-2 diabetes mellitus: the Rotterdam
      Study.
AB  - The aim of this study was to determine the association between type-2 diabetes
      mellitus (DM), BMD and fractures in 6,655 men and women aged 55 years and over
      from the Rotterdam Study. We compared subjects with type-2 DM to subjects without
      DM. Additionally, subset analyses were performed, dividing subjects on the basis
      of the glucose tolerance test into already treated DM, newly diagnosed DM,
      impaired glucose tolerance (IGT) and normal glucose tolerance (NGT, reference).
      Femoral neck and lumbar spine BMD were measured using DEXA. Nonvertebral fracture
      ascertainment was performed using an automated record system involving GPs and
      local hospitals. Although subjects with DM had higher BMD, they had an increased
      nonvertebral fracture risk: hazard ratio (HR) 1.33 (1.00-1.77). In subset
      analysis, the increased fracture risk appeared restricted to treated DM subjects
      only: HR 1.69 (1.16-2.46). Subjects with IGT had a higher BMD, but contrary to
      treated DM, they had a lower fracture risk: HR 0.80 (0.63-1.00). In conclusion,
      subjects with type-2 DM and IGT both have a higher BMD. Whereas, subjects with
      IGT have a decreased fracture risk, subjects with DM (primarily those with
      already established and treated DM) had an increased fracture risk, probably due
      to long-term complications associated with DM.

PMID- 15940396
TI  - Chronic traumatic diaphragmatic hernia with pericardial rupture and associated
      gastroesophageal reflux.
AB  - Major thoracic and abdominal trauma damages the diaphragm 5% of the time. These
      injuries may be recognized when they occur but often are discovered months later
      during work up for related symptoms. Typically, the injury is to the left
      posterolateral aspect of the diaphragm. Rarely, rupture through the central
      diaphragmatic tendon into the pericardial space occurs and this results in
      different symptoms than the more common injury. We present the case of a patient
      who presented with chest pain, near syncopal episodes and refractory
      gastroesophageal reflux years after he was struck by a car and hospitalized.
      Radiographic imaging included a chest CT that demonstrated herniation of the
      transverse colon into the mediastinum. During exploration, a defect in the
      central diaphragm was found with free communication between the peritoneal and
      pericardial spaces. In this paper, we review our management of this unusual
      diaphragmatic hernia and the unique symptoms associated with it.

PMID- 15940397
TI  - Treating the banana fold with the dermotuberal anchorage technique: case report.
AB  - The banana fold, or the infragluteal fold, is a fat deposit on the posterior
      thigh close to the gluteal crease and parallel to it. A banana fold may form for
      different reasons, among which an iatrogenic cause is recurrent. Although banana
      fold is a common problem, unrelished by most women, few procedures are targeted
      specifically to fight it. This report presents a severe case of iatrogenic banana
      fold corrected by a modification of the dermotuberal anchorage buttock-lifting
      technique, as reported by the author for gluteal ptosis. The operation is
      performed by tucking in part of the banana fold tissue caudal to the gluteal
      crease, sliding that tissue, after depithelization, under the buttock, and
      pulling it up toward the ischial tuberosity until the redundant skin on the
      posterior thigh is tight and the banana fold is reduced. Assessment of the
      results 1 year after surgery showed that the technique provided a good scar kept
      within the subgluteal crease, and that it satisfactorily corrected the patient's
      major complaint: the banana-shaped fold.

PMID- 15940398
TI  - Adaptive capacity and community-based natural resource management.
AB  - Why do some community-based natural resource management strategies perform better
      than others? Commons theorists have approached this question by developing
      institutional design principles to address collective choice situations, while
      other analysts have critiqued the underlying assumptions of community-based
      resource management. However, efforts to enhance community-based natural resource
      management performance also require an analysis of exogenous and endogenous
      variables that influence how social actors not only act collectively but do so in
      ways that respond to changing circumstances, foster learning, and build capacity
      for management adaptation. Drawing on examples from northern Canada and Southeast
      Asia, this article examines the relationship among adaptive capacity, community
      based resource management performance, and the socio-institutional determinants
      of collective action, such as technical, financial, and legal constraints, and
      complex issues of politics, scale, knowledge, community and culture. An emphasis
      on adaptive capacity responds to a conceptual weakness in community-based natural
      resource management and highlights an emerging research and policy discourse that
      builds upon static design principles and the contested concepts in current
      management practice.

PMID- 15940399
TI  - Application of a physical input-output table to evaluate the development and
      sustainability of continental water resources in Spain.
AB  - Continental waters are complex resources in terms of a measurable physical
      quantity, and measuring them requires a good knowledge of total water
      availability. In this research, an accounting physical input-output table (PIOT)
      was applied to evaluate total water resources and gross annual availabilities at
      each stage of the natural-artificial water cycle. These stages are considered
      subsystems of a continental water resource system describing water transfers for
      an average year within 13 administrative basins of Spain. Water transfers between
      various subsystems are characterized by internal flows decreasing the water
      resource availabilities. The PIOT analysis establishes these internal flows, and
      the origins and final uses of the total resources for each subsystem. The input
      output balance registered an unsustainable negative net accumulation in eight
      water basins. The PIOT analysis also allowed the calculation of significant
      indicators such as water resource developments (RDI) and their sustainable use
      (SUI). RDI and SUI demonstrate that groundwater is a critical resource affecting
      the environment (e.g., wetlands in the upper Guadiana) and the water supply
      (e.g., irrigation in the Segura basin). The results of this model suggest that
      above-/below-ground hydrological links are important when decisions have to be
      made in order to provide a satisfactory supply of water in Spain. The model
      integrates the different water basins under territorial criteria, and therefore
      it may be useful for the Spanish National Hydrological Plan.

PMID- 15940400
TI  - Phreatophytic vegetation and groundwater fluctuations: a review of current
      research and application of ecosystem response modeling with an emphasis on great
      basin vegetation.
AB  - Although changes in depth to groundwater occur naturally, anthropogenic
      alterations may exacerbate these fluctuations and, thus, affect vegetation
      reliant on groundwater. These effects include changes in physiology, structure,
      and community dynamics, particularly in arid regions where groundwater can be an
      important water source for many plants. To properly manage ecosystems subject to
      changes in depth to groundwater, plant responses to both rising and falling
      groundwater tables must be understood. However, most research has focused
      exclusively on riparian ecosystems, ignoring regions where groundwater is
      available to a wider range of species. Here, we review responses of riparian and
      other species to changes in groundwater levels in arid environments. Although
      decreasing water tables often result in plant water stress and reduced live
      biomass, the converse is not necessarily true for rising water tables. Initially,
      rising water tables kill flooded roots because most species cannot tolerate the
      associated low oxygen levels. Thus, flooded plants can also experience water
      stress. Ultimately, individual species responses to either scenario depend on
      drought and flooding tolerance and the change in root system size and water
      uptake capacity. However, additional environmental and biological factors can
      play important roles in the severity of vegetation response to altered
      groundwater tables. Using the reviewed information, we created two conceptual
      models to highlight vegetation dynamics in areas with groundwater fluctuations.
      These models use flow charts to identify key vegetation and ecosystem properties
      and their responses to changes in groundwater tables to predict community
      responses. We then incorporated key concepts from these models into EDYS, a
      comprehensive ecosystem model, to highlight the potential complexity of
      predicting community change under different fluctuating groundwater scenarios.
      Such models provide a valuable tool for managing vegetation and groundwater use
      in areas where groundwater is important to both plants and humans, particularly
      in the context of climate change.

PMID- 15940401
TI  - A risk-based predictive tool to prevent accidental introductions of nonindigenous
      marine species.
AB  - Preventing the introduction of nonindigenous species (NIS) is the most efficient
      way to avoid the costs and impacts of biological invasions. The transport of
      fouling species on ship hulls is an important vector for the introduction of
      marine NIS. We use quantitative risk screening techniques to develop a predictive
      tool of the abundance and variety of organisms being transported by ocean-going
      yachts. We developed and calibrated an ordinal rank scale of the abundance of
      fouling assemblages on the hulls of international yacht hulls arriving in New
      Zealand. Fouling ranks were allocated to 783 international yachts that arrived in
      New Zealand between 2002 and 2004. Classification tree analysis was used to
      identify relationships between the fouling ranks and predictor variables that
      described the maintenance and travel history of the yachts. The fouling ranks
      provided reliable indications of the actual abundance and variety of fouling
      assemblages on the yachts and identified most (60%) yachts that had fouling on
      their hulls. However, classification tree models explained comparatively little
      of the variation in the distribution of fouling ranks (22.1%), had high
      misclassification rates (approximately 43%), and low predictive power. In
      agreement with other studies, the best model selected the age of the toxic
      antifouling paint on yacht hulls as the principal risk factor for hull fouling.
      Our study shows that the transport probability of fouling organisms is the result
      of a complex suite of interacting factors and that large sample sizes will be
      needed for calibration of robust risk models.

PMID- 15940402
TI  - On the design of computer-based models for integrated environmental science.
AB  - The current research agenda in environmental science is dominated by calls to
      integrate science and policy to better understand and manage links between social
      (human) and natural (nonhuman) processes. Freshwater resource management is one
      area where such calls can be heard. Designing computer-based models for
      integrated environmental science poses special challenges to the research
      community. At present it is not clear whether such tools, or their outputs,
      receive much practical policy or planning application. It is argued that this is
      a result of (1) a lack of appreciation within the research modeling community of
      the characteristics of different decision-making processes including policy,
      planning, and (2) participation, (3) a lack of appreciation of the
      characteristics of different decision-making contexts, (4) the technical
      difficulties in implementing the necessary support tool functionality, and (5)
      the socio-technical demands of designing tools to be of practical use. This
      article presents a critical synthesis of ideas from each of these areas and
      interprets them in terms of design requirements for computer-based models being
      developed to provide scientific information support for policy and planning.
      Illustrative examples are given from the field of freshwater resources
      management. Although computer-based diagramming and modeling tools can facilitate
      processes of dialogue, they lack adequate simulation capabilities. Component
      based models and modeling frameworks provide such functionality and may be suited
      to supporting problematic or messy decision contexts. However, significant
      technical (implementation) and socio-technical (use) challenges need to be
      addressed before such ambition can be realized.

PMID- 15940403
TI  - Public participation mechanisms in environmental disasters.
AB  - This paper examines the role of public participation mechanisms in certain major
      environmental disasters. It examines situations in which people's lifestyles or
      their lives have been directly threatened, and thus elicited citizen
      participation. Threatening issues often seem morally, physically, socially,
      economically, religiously, and otherwise unacceptable to a group. As will be
      presented in this paper, citizens voluntarily participate in a community activity
      when they see that their way of life has been threatened. An introductory
      historical perspective, the legal framework upon which it is based, and
      background information on the participatory mechanisms, all emphasizing the
      importance and need for empowering citizens with participatory skills so as to
      bring changes in the existing educational, legal, and social systems are
      presented. The major environmental accidents/disasters of Minamata, Japan;
      Bhopal, India; Seveso, Italy; Chernobyl, Ukraine; and Exxon-Valdez, Alaska are
      discussed, mainly to indicate the reaction, and the participatory mechanisms used
      by the affected communities in each of the sudden disasters that occurred. If
      citizens worldwide had been active participants in the environmental issues, it
      is quite possible that we would have experienced fewer environmental accidents.

PMID- 15940404
TI  - Consensus Seasonal Flood Forecasts and Warning Response System (FFWRS): an
      alternate for nonstructural flood management in Bangladesh.
AB  - Despite advances in short-range flood forecasting and information dissemination
      systems in Bangladesh, the present system is less than satisfactory. This is
      because of short lead-time products, outdated dissemination networks, and lack of
      direct feedback from the end-user. One viable solution is to produce long-lead
      seasonal forecasts--the demand for which is significantly increasing in
      Bangladesh--and disseminate these products through the appropriate channels. As
      observed in other regions, the success of seasonal forecasts, in contrast to
      short-term forecast, depends on consensus among the participating institutions.
      The Flood Forecasting and Warning Response System (henceforth, FFWRS) has been
      found to be an important component in a comprehensive and participatory approach
      to seasonal flood management. A general consensus in producing seasonal forecasts
      can thus be achieved by enhancing the existing FFWRS. Therefore, the primary
      objective of this paper is to revisit and modify the framework of an ideal
      warning response system for issuance of consensus seasonal flood forecasts in
      Bangladesh. The five-stage FFWRS-i) Flood forecasting, ii) Forecast
      interpretation and message formulation, iii) Warning preparation and
      dissemination, iv) Responses, and v) Review and analysis-has been modified. To
      apply the concept of consensus forecast, a framework similar to that of the
      Southern African Regional Climate Outlook Forum (SARCOF) has been discussed.
      Finally, the need for a climate Outlook Fora has been emphasized for a
      comprehensive and participatory approach to seasonal flood hazard management in
      Bangladesh.

PMID- 15940405
TI  - A rapid decision-making method for the evaluation of pollution-sensitive coastal
      areas in the Mediterranean sea.
AB  - Places of natural beauty and/or cultural value in the Mediterranean Sea are
      presenting adverse effects due to pollution. These environmental threats caused
      by point and nonpoint sources are mainly the reason why these areas represent
      "pollution-sensitive areas," where the risk of deterioration is immediate.
      However, the risk will decrease and eventually disappear if protective measures
      are applied. In the present article, a multicriteria decision-making method is
      proposed for the prioritization of the Mediterranean sensitive coastal areas,
      taking into consideration criteria of pollution risk such as impact on human
      health, aquatic ecosystems, and socioeconomic value of the area. Weighting
      factors were then attributed to the different criteria according to their
      regional priorities, and a total pollution risk score was calculated for every
      sensitive area. However, some sensitive areas are more vulnerable than others
      because of their natural characteristics. Therefore, the total pollution risk
      score was then multiplied by a vulnerability weighting factor and a Total
      Sensitivity Score was calculated for every sensitive area. With this method,
      Mediterranean sensitive areas in coastal zones can be ranked on a priority list
      and then categorized according to their "sensitivity," in a way that decision
      makers can select the most urgent cases to direct their attention for the
      effective protection of the Mediterranean marine environment. The method is rapid
      and practicable and has already been used with existing data and information in
      several Mediterranean countries.

PMID- 15940406
TI  - Gamma knife radiosurgery for circumscribed choroidal hemangioma.
AB  - The authors report a case of circumscribed choroidal hemangioma (CCH) treated by
      stereotactic radiosurgery with gamma knife. A thirteen-year-old boy presented
      with a 4-year history of progressive visual loss in his right eye. Because of the
      large size and fluid collection under the macula, gamma knife radiosurgery was
      done. During 2 years of follow-up, there was resolution of retinal detachment,
      regression in tumor thickness, and no complications. Gamma knife radiosurgery may
      be a reasonable alternative treatment option for symptomatic CCHs which are
      difficult to manage using standard therapeutic options such as photocoagulation.

PMID- 15940409
TI  - Nosocomial infections in intensive care units.

PMID- 15940410
TI  - New fluoroquinolones in lower respiratory tract infections and emerging patterns
      of pneumococcal resistance.
AB  - The increasing resistance of Streptococcus pneumoniae, the most important
      community respiratory pathogen, to beta-lactams and other first-line
      antimicrobial agents usually employed for the empirical treatment of lower
      respiratory tract infections has led to the inclusion, in several current
      guidelines, of a fluoroquinolone with improved activity against pneumococci as
      the first choice agent for the management of such infections. The excellent
      microbiological, pharmacokinetic, and pharmacodynamic characteristics of the new
      fluoroquinolones (levofloxacin, moxifloxacin, gemifloxacin, and gatifloxacin)
      have encouraged their growing use, probably contributing to the emergence of
      fluoroquinolone-resistant pneumococci; although pneumococcal resistance to new
      fluoroquinolones is currently low, there is still concern about the potential for
      widespread emergence of resistance to these agents if they become
      indiscriminately used. Levofloxacin clinical failures have already been reported
      in the management of patients with pneumococcal community-acquired pneumonia;
      development of resistance in clinical isolates of S. pneumoniae has prompted a
      critical reexamination of the newer fluoroquinolones to assess their potency and
      to preserve their activity. An understanding of the pharmacokinetic and
      pharmacodynamic properties, allowing selection of the most potent
      fluoroquinolone, will reduce the opportunity for resistance to develop. Finally,
      a targeted use of these agents will maintain class efficacy.

PMID- 15940411
TI  - Periodic surveillance of nosocomial infections in a neurosurgery intensive care
      unit.
AB  - BACKGROUND: We assessed data on the epidemiology of nosocomial infections (NIs)
      in a 14-bed neurosurgical intensive care unit (NSICU) and used surveillance data
      for the promotion of quality improvement activities. PATIENTS AND METHODS:
      Prospective periodic surveillance was performed over five 3-month periods between
      July 1998 and October 2002 on all patients admitted with a length of stay > 24
      hours. RESULTS: 763 patients with a total of 4,512 patient days and a mean length
      of stay of 5.9 days were enrolled within the 15-month study period. A total of 93
      NIs were identified in 82 patients. Urinary tract infections (24.7%), pneumonia
      (23.6%), and bloodstream infections (17.2%) were the most frequent NIs recorded.
      Device-associated incidence rates were 6.0 (3.8-9.0, CI(95%)) for urinary tract
      infection, 4.4 (2.4-7.4, CI(95%)) for bloodstream infection, and 10.3 (6.3-15.9,
      CI(95%)) for pneumonia per 1,000 days at risk. For improvement of infection
      control-related processes, evidence-based infection control guidelines were
      established and an NSICU nurse was designated to be responsible for infection
      control issues on the ward. In addition, several infection control problems arose
      during the observation periods and were rapidly responded to by introducing
      specific intervention strategies. CONCLUSION: Periodic surveillance is a valuable
      tool for assessing the epidemiology of NIs in the NSICU setting as well as for
      promoting the initiation of quality improvement activities.

PMID- 15940412
TI  - Epidemiology of severe sepsis in intensive care units in the Slovak Republic.
AB  - BACKGROUND: We investigated the number, clinical characteristics, and outcomes of
      ICU patients, who met precise clinical and physiological criteria for severe
      sepsis (as defined in the PROWESS study) in Slovak intensive care units. We
      designed an observational cohort epidemiological study with retrospective
      analysis of prospectively collected data. 12 adult general intensive care units
      participated in the Slovak Republic between July and December 2002. PATIENTS AND
      METHODS: Patients included 1,533 adult ICU admissions during the second half of
      2002 in 12 adult ICUs. Descriptive statistical methods (independent sample T
      test, chi(2) test, and linear Pearson coefficient of correlation) were used.
      RESULTS: We found that 7.9% of hospitalized critically ill patients met severe
      sepsis criteria in the intensive care units. The most frequent primary sources of
      infection were lungs and abdomen. Hospital mortality of severe septic patients
      was 51.2% (62 pts/121 pts). Most patients (85.1%) were > 40 years of age.
      Mortality increased with age; mean average age of survivors (53 years) was
      significantly lower than in nonsurvivors (61 years, p = 0.01). Factors associated
      with mortality were age over 50 years, three or more dysfunctional organs, and
      elevated admission and maximum SOFA scores. Survivors had a significantly lower
      number of sites with organ system dysfunction (MODS 2.56) than nonsurvivors (MODS
      3.98). SOFA score seems to be a valuable tool to differentiate survivors from
      nonsurvivors. All the septic patients had SOFA scores greater than 4 points.
      Survivors of severe sepsis were characterized with significantly lower admission
      and maximum SOFA scores (median 8.7 and 9.4 points, respectively) than septic
      nonsurvivors (median 11.6 and 14.0 points, respectively, p = 0.001). CONCLUSION:
      We estimate 1,770 cases of severe sepsis hospitalized at Slovak adult intensive
      care units per year. Hospital mortality for severe sepsis remains very high
      (51.2%) and is associated with advanced age (over 50 years), number of failing
      organs and higher admission and maximum SOFA scores.

PMID- 15940413
TI  - Hospital-acquired pneumonia in critically ill patients: factors associated with
      episodes due to imipenem-resistant organisms.
AB  - BACKGROUND: Inadequate initial antimicrobial therapy represents one of the
      factors associated with mortality of patients suffering from hospital-acquired
      pneumonia. According to its wide antimicrobial spectrum, imipenem belongs to the
      usual antibiotics proposed by current guidelines for such a therapy. However,
      major changes in the antibiotic susceptibility patterns of bacteria in the
      intensive care unit (ICU) have occurred. Our goal was to determine the incidence
      of hospital-acquired pneumonia (HAP) due to imipenem-resistant organism(s) in our
      ICU and to identify factors associated with such a resistance. PATIENTS AND
      METHODS: From January 1994 to December 2001, all consecutive patients admitted to
      our ICU for HAP or exhibiting HAP during their ICU stay were included in an
      observational cohort. Patients with a bacteriologically documented HAP were
      studied. For each causative pathogen, imipenem susceptibility was routinely
      determined. Patients with an HAP episode due to at least one imipenem-resistant
      causative organism were compared with patients who developed HAP in which all
      incriminated pathogens were imipenem susceptible. RESULTS: 235 patients were
      included in our observational cohort. Among them, 168 had an HAP episode with a
      bacteriologically proven infection. In 42 patients (25%), at least one causative
      organism was resistant to imipenem. The 44 imipenem-resistant organisms were
      Staphylococcus aureus (n = 15), Pseudomonas aeruginosa (n = 14), Stenotrophomonas
      maltophilia (n = 13), and Acinetobacter baumannii (n = 2). Multivariate analysis
      identified four significant independent factors associated with resistance of
      causative organism(s) to imipenem: prior use of a fluoroquinolone (AOR = 3.9; 95%
      CI: 1.8 to 8.8; p < 0.0001), prior use of an aminoglycoside (AOR = 2.6; CI: 1.2
      to 5.9; p = 0.02), use of invasive blood pressure monitoring (AOR = 2.7; CI: 1.0
      to 7.0; p = 0.04) and bilateral chest X-ray involvement (AOR = 2.6; CI: 1.1 to
      5.8; p = 0.02). CONCLUSION: Factors associated with potential inadequacy of
      imipenem used as the single antibiotic for initial empiric treatment for HAP were
      identified. When they are present, imipenem should be either combined with
      antibiotics such as vancomycin and ciprofloxacin or replaced with another broad
      spectrum antimicrobial regimen.

PMID- 15940414
TI  - Increased incidence of fulminant hepatic failure in previously unrecognized HBsAg
      carriers with acute hepatitis independent of etiology.
AB  - BACKGROUND: Previous studies have shown a high risk of fulminant hepatitis in
      HBsAg carriers with acute hepatitis. The etiology of acute hepatitis in HBsAg
      carriers was heterogeneous. This study aimed to correlate the incidence of
      fulminant hepatitis with the etiology in HBsAg carriers with acute hepatitis.
      PATIENTS AND METHODS: The incidence of fulminant hepatitis was studied in 334
      adults hospitalized for overt acute viral hepatitis. There were 12 patients with
      acute hepatitis A, 17 with acute hepatitis B, 70 with acute hepatitis C, five
      with acute hepatitis E, 53 with acute hepatitis non-A-E, and 177 previously
      unrecognized HBsAg carriers with acute hepatitis (patients who were positive for
      HBsAg but negative for IgM antibody against hepatitis B core antigen). Of the
      latter, 64 (36%) had serological evidence of non-B hepatotropic virus
      superinfection. RESULTS: The incidence of fulminant hepatitis was 3.2% (5/157) in
      patients with acute hepatitis A, B, C, E or non-A-E, and 20.3% (36/177) in HBsAg
      carriers with acute hepatitis (p < 0.001). HBsAg carriers were at a 9-fold
      increased risk of fulminant hepatitis than noncarriers. Among HBsAg carriers with
      acute hepatitis, the incidence of fulminant hepatitis showed no significant
      difference between patients with viral superinfection (23% or 15/64) and those
      without (19% or 21/113). The incidence of fulminant hepatitis in HBsAg carriers
      with viral superinfection also showed no significant difference between different
      etiologies of virus superinfection. CONCLUSION: There is a 9-fold increased risk
      of fulminant hepatitis in HBsAg carriers with acute hepatitis, independent of the
      underlying etiology.

PMID- 15940415
TI  - Treatment of HIV-1-associated Kaposi's sarcoma with pegylated liposomal
      doxorubicin and HAART simultaneously induces effective tumor remission and CD4+ T
      cell recovery.
AB  - BACKGROUND: The combination of highly active antiretroviral therapy (HAART) and
      liposomal doxorubicin is a promising approach for the treatment of progressive
      HIV-related Kaposi's sarcoma (KS). Here, we determined the safety, tolerability,
      and efficacy of liposomal doxorubicin and HAART as a combined treatment approach
      for advanced KS, and assessed the impact of liposomal doxorubicin on HAART
      mediated immune reconstitution and viral suppression. PATIENTS AND METHODS: In an
      uncontrolled observational trial, KS treatment responses were assessed in 54 HIV
      1-infected patients with advanced KS according to ACTG criteria. Immunological
      and virological treatment responses were compared to 54 non-KS-affected HIV-1
      patients who were individually matched to the study participants according to
      sex, age (+/- 5 years), CD4+ T cell count (+/- 25%), HIV RNA load (+/- 25%) and
      previous antiretroviral therapy exposure. RESULTS: In 81.5% of the study
      patients, complete or partial responses were observed within a median of 8 weeks.
      Treatment-related side effects were predominantly confined to leukopenia (44.4%
      of patients) and mild-to-moderate liver enzyme elevation (22.3% of patients).
      Relative CD4+ T cell counts increased to a similar degree both in study patients
      and matched pairs (7% vs 6%, respectively), yet, absolute CD4+ T cell counts
      augmented considerably stronger in chemotherapy-naive matched pairs than in the
      study patients. CONCLUSION: The simultaneous administration of HAART and
      liposomal doxorubicin is a safe and effective treatment approach for advanced KS
      and HAART-mediated recovery of relative CD4+ T cell counts does not seem to be
      impaired by concomitant treatment with liposomal doxorubicin.

PMID- 15940416
TI  - Rapidly destructive Staphylococcus epidermidis endocarditis.
AB  - A 29-year-old man with rapidly destructive Staphylococcus epidermidis
      endocarditis after mitral valve reconstruction is presented. Resistance to
      rifampin and teicoplanin occurred during antibiotic treatment resulting in
      clinical failure and valve destruction. Subsequently, the patient was
      successfully treated, by combining valve replacement with antibiotic therapy
      including quinupristin/dalfopristin, levofloxacin, and vancomycin. In conclusion,
      S. epidermidis can cause rapid valve destruction with large vegetations, and
      combination of surgery and antibiotic therapy may be necessary.

PMID- 15940417
TI  - Possibly linezolid-induced peripheral and central neurotoxicity: report of four
      cases.
AB  - BACKGROUND: Linezolid is the first member of the new synthetic class of
      antibacterial agents that prevent the formation of the 70S ribosomal subunit. It
      represents an attractive choice in the therapeutic arsenal because it is
      effective against methicillin-resistant strains of Staphylococcus spp. Adverse
      hematological events have been reported. They are rapidly reversible after
      discontinuation of treatment and usually occur during treatment courses of more
      than 2 weeks. The advised duration of linezolid use is 28 days and the
      consequences of prolonged use are unknown. In addition, this drug has some
      dopaminergic properties that can induce the serotonin syndrome if a monoamine
      oxidase inhibitor is used simultaneously. PATIENTS AND METHODS: Since linezolid
      became available for use in 2002, four cases of probable central and peripheral
      linezolid-induced neurotoxicity have been recorded in our unit. RESULTS: Two de
      novo peripheral neuropathies and one worsening of a preexisting toxic neuropathy
      have been observed. In each case, linezolid therapy was used during a prolonged
      duration of 8, 23, and 24 weeks, respectively. First neurological signs appeared
      in one case during the 2nd week of treatment and beyond the 1st month in the
      other cases. To date, all cases of peripheral neuropathy resulted in persistent
      neurological damage after discontinuation of linezolid. Assessments did not
      reveal any other explanation for these neurological impairments. Another case
      concerned a patient who developed transient encephalopathy attributed to
      linezolid during a coadministration with hydroxyzine. CONCLUSION: Linezolid may
      induce persistent peripheral neuropathy after prolonged use and may cause a
      transient central neurotoxicity in combination with an anticholinergic agent,
      such as an antihistamine. Close neurological monitoring should be recommended in
      prolonged linezolid therapy and coadministration of a serotonin reuptake
      inhibitor or antihistamine should be avoided to limit neurological adverse
      events.

PMID- 15940418
TI  - Linezolid contributed to Clostridium difficile colitis with fatal outcome.
AB  - Linezolid, the first of a new class of antibacterial drugs, the oxazolidinones,
      has inhibitory activity against a broad range of gram-positive aerobic cocci and
      also against certain anaerobes. Although diarrhea is one of the most frequently
      encountered adverse effects of linezolid, Clostridium difficile-related
      complications are very uncommon. One case of fatal C. difficile colitis in a
      patient with spondylodiscitis, who had received a long-term course of linezolid
      therapy, is presented. Colitis was able to be exclusively assigned to linezolid.
      Factors contributing to the colitis are discussed.

PMID- 15940419
TI  - Tick-borne encephalitis in Friuli Venezia Giulia, northeastern Italy.

PMID- 15940420
TI  - Susceptibility to HIV/AIDS: an individual characteristic we can measure?
AB  - Susceptibility to HIV-1 infections is, beside other factors, determined by
      individual host genetic variants like HLA class I alleles, CCR5 and CCR2 variants
      and levels of CCR5 binding chemokines. A new approach to determine the individual
      risk of acquiring an HIV infection or to estimate the disease progression could
      now be possible. In a recent study, a significant interindividual and
      interpopulation difference in the copy number of a segmental duplication
      encompassing the gene encoding CCL3L1, a potent human immunodeficiency virus-1
      (HIV- 1)-suppressive chemokine was found. Possession of a CCL3L1 copy number
      lower than the population average was associated with markedly enhanced
      HIV/acquired immunodeficiency syndrome (AIDS) susceptibility. This could lead to
      a screening test that identifies people who have a higher or lower susceptibility
      to HIV/ AIDS, potentially enabling clinicians to adapt treatment regimens. Also,
      this is particularly important for assessment of the efficacy of a protective
      vaccine.

PMID- 15940421
TI  - Two-beam optical traps: refractive index and size measurements of microscale
      objects.
AB  - A counter-propagating optical trap measurement (COTM) system is proposed and
      analyzed based on the ray-optics model. In this system, refractive index and size
      of trapped objects can be estimated by using forward scattered light from the two
      beam laser trap with resolution Delta n = 0.013 for the refractive index
      measurements and 3.3% for the size measurements, which is comparable with current
      bulk techniques, such as refractometry, and flow cytometry. The unique advantage
      of the COTM system over conventional approaches lies in its capability of marker
      free single-particle characterization in whatever transparent buffer required by
      living cell, eliminating the necessity of changing the fluid composition of the
      sample in refractometry, and of tagging target with toxic fluorescence dyes in
      flow cytometry. Noise analysis predicts a potential improvement in the system
      resolution by more than two orders of magnitude. This non-invasive and sterile
      tool complements lab-on-a-chips with single cell manipulation and analysis in
      living friendly ambient.

PMID- 15940422
TI  - Modeling and optimization of high-sensitivity, low-volume microfluidic-based
      surface immunoassays.
AB  - Microfluidics are emerging as a promising technology for miniaturizing biological
      assays for applications in diagnostics and research in life sciences because they
      enable the parallel analysis of multiple analytes with economy of samples and in
      short time. We have previously developed microfluidic networks for surface
      immunoassays where antibodies that are immobilized on one wall of a microchannel
      capture analytes flowing in the microchannel. This technology is capable of
      detecting analytes with picomolar sensitivity and from sub-microliter volume of
      sample within 45 min. This paper presents the theoretical modeling of these
      immunoassays where a finite difference algorithm is applied to delineate the role
      of the transport of analyte molecules in the microchannel (convection and
      diffusion), the kinetics of binding between the analyte and the capture
      antibodies, and the surface density of the capture antibody on the assay. The
      model shows that assays can be greatly optimized by varying the flow velocity of
      the solution of analyte in the microchannels. The model also shows how much the
      analyte-antibody binding constant and the surface density of the capture
      antibodies influence the performance of the assay. We then derive strategies to
      optimize assays toward maximal sensitivity, minimal sample volume requirement or
      fast performance, which we think will allow further development of microfluidic
      networks for immunoassay applications.

PMID- 15940423
TI  - Wireless spectroscopic compact photonic explorer for diagnostic optical imaging.
AB  - A remote, small-size spectroscopic-based device called Compact Photonics Explorer
      (CPE) was designed, assembled, and tested for medical and non-medical
      spectroscopic and imaging applications. Spatial images acquired using the
      spectroscopic CPE are presented. Operational principles are demonstrated for
      various biomedical and non-medical applications.

PMID- 15940424
TI  - Microreactor microfluidic systems with human microsomes and hepatocytes for use
      in metabolite studies.
AB  - In the area of drug discovery, high-speed synthesis has increased the number of
      drug candidates produced. These potential drugs need to be evaluated for their
      adsorption, distribution, metabolism, elimination, and toxicology (ADMET)
      properties as early in the drug development stage as possible. Previously, a
      potential drug's ADMET properties have been found out by using monolayer cell
      cultures and live animals. These methods can be costly, time-intensive, and
      impractical for screening the large amount of potential drugs created by
      combinatorial chemistry. A quick, small, inexpensive, and highly parallel device
      would be desirable to determine a drug candidate's properties (i.e., metabolism
      of the drug). Here we fabricate a microfluidic device entrapping human microsomes
      within poly(ethylene) glycol hydrogels thereby generating an in situ microreactor
      to assess a drug candidate's metabolic properties that can be coupled to analysis
      equipment. We show that microsomes can be entrapped without the loss of enzymatic
      activity during photopolymerization. Additionally, a microreactor utilizing
      hepatocytes was also created for comparison with the microsome microreactor.

PMID- 15940425
TI  - Editorial.

PMID- 15940427
TI  - Analysis of electro-osmotic flow characteristics at joint of capillaries with
      step change in zeta-potential and dimension.
AB  - The Navier-Stokes equation was used to describe the characteristics of electro
      osmotic flow. The corresponding numerical simulations were performed for varying
      zeta-potential and dimension. The results indicated that a step change in zeta
      potential will cause a significant variation in the velocity profile and pressure
      distribution of the flow. A step change both in zeta-potential and dimension will
      result in a more violent variation near the joint of the capillary. This
      variation will reduce the separation efficiency and quality of capillary
      electrophoresis. The conclusions are helpful to design and fabrication of
      microfluidic devices, the analysis of data collected from such devices and
      improvement of the separation efficiency of capillary electrophoresis.

PMID- 15940428
TI  - New method for DNA microarrays development: applied to human platelet antigens
      polymorphisms.
AB  - DNA microarrays are a powerful experimental tool for the detection of specific
      genomic sequences and are invaluable to a broad array of applications: clinical
      diagnosis, personalized medicine, drug research and development, gene therapy,
      food control technologies, and environmental sciences. Alloimmunization to human
      platelet antigens (HPAs) is commonly responsible for neonatal alloimmune
      thrombocytopenia, post-transfusional purpura and platelet transfusion
      refractoriness. Using DNA microarrays, we developed a diagnosis to type the
      biallelic HPA-1 platelet group. The region for the human genomic DNA sequence
      that contains the polymorphism responsible for HPA-1 alleles was amplified by
      polymerase chain reaction (PCR). The expected DNA fragments were hybridized on
      DNA microarrays, and the data were analyzed using specially developed software.
      Our initial results show that the two HPA-1 antigens polymorphisms containing a
      single base difference were detected using DNA microarrays.

PMID- 15940429
TI  - Parallel detection and quantification using nine immunoassays in a protein
      microarray for drug from serum samples.
AB  - A protein microarray system for detection and quantification of nine prohibited
      drugs in serum is described. Chemically modified slides were chosen as the
      microarray substrates because of their suitable for drug-BSA printing. The
      developed protein microarray was able to preserve the biological function of the
      haptens, when immobilized on the microarray surface and demonstrated binding with
      their corresponding antibodies. The microarray could also be used for
      quantitative analysis when mouse IgG was chosen as an internal control for data
      processing. There was no qualitative difference between the results obtained
      using the protein microarray and ELISA. The protein microarray technology should
      be applicable to performing, simultaneously, large scale screening tests for many
      different analytes in serum.

PMID- 15940430
TI  - Microfluidic genetic analysis with an integrated a-Si:H detector.
AB  - We have developed an integrated hydrogenated amorphous silicon (a-Si:H)
      fluorescence detector for microfluidic genetic analysis. It consists of a half
      ball lens, a ZnS/YF3 multilayer optical interference filter with a pinhole, and
      an annular a-Si:H PIN photodiode allowing the laser excitation to pass up through
      the central aperture in the photodiode and the filter. Microfluidic separations
      of multiplex PCR products generated from methicillin-resistant/sensitive
      Staphylococcus aureus (MRSA/MSSA) DNA on microfluidic capillary electrophoresis
      (CE) devices are successfully detected with the integrated detector. Similarly,
      multiplex PCR amplicons from the kanamycin resistant and K12 serotype-specific
      genes of E. coli cells are detected. The direct detection of multiplex PCR
      amplicons indicates that the fluorescence detector can be successfully coupled
      with current microfluidic PCR-CE platforms. This work establishes that the
      integrated a-Si:H detector provides relevant limits of detection for point-of
      care genetic and pathogen analysis with microfluidic devices.

PMID- 15940431
TI  - The synthesis of GoldMag nano-particles and their application for antibody
      immobilization.
AB  - Fe3O4/Au (GoldMag) particles with core/shell structure were synthesized by
      reduction of Au3+ with hydroxylamine in the presence of Fe3O4. The synthesized
      particles have an average size smaller than 100 nm in diameter with of
      superparemagnetic properties due to their Fe oxide cores. The particles show
      optical features with a plasmon resonance peak from 550, 570 to 590 nm
      correlating with increasing diameters from 50 nm, 70 nm to 100 nm. The GoldMag
      particles need only a single step for antibody immobilization and have high
      binding capacity for antibodies. These advantages permit improved methods of
      isolating and detecting biomolecules.

PMID- 15940432
TI  - Design and simulation of active biochip system.
AB  - To solve the problems existing in passive biochip systems, we designed a novel
      active biochip system. This system introduces negative pressure and controlling
      devices to adjust the antigen-antibody reaction on the nitrocellulose membrane.
      Computational simulation demonstrated that this system is a rapid, stable, robust
      and practical system that may enhance the efficiency of antigen-antibody
      reactions and improve the repeatability and accuracy of biochip analysis.

PMID- 15940433
TI  - Fifteenth Meeting of the European Neurological Society, 18-22 June 2005, Vienna,
      Austria. Abstracts.

PMID- 15940436
TI  - Foreign body in the airway: unusual cause of acute dyspnoe after cardiac surgery.
AB  - We report on a 68-year-old male who presented with acute onset of dyspnoea and
      cough. After coronary artery bypass grafting and mitral valve repair with an
      annuloplasty ring, postoperative recovery was initially uneventful. On the 6th
      postoperative day, he came back to intensive care unit due to acute dyspnoea.
      Fig. 1 demonstrates chest x-ray. We identified the foreign body as a dental
      prosthesis (Fig. 2). Removal from the right bronchial tree was successful using a
      flexible bronchoscope under local anesthesia; intubation was not required. This
      procedure was safe and well tolerated by the patient. Clinical presentation of
      adult foreign body aspiration are often nonspecific. Chest x-ray is very helpful
      for identification and localization of foreign bodies in the airway. Extraction
      can be performed with flexible or rigid bronchoscopy. For the removal, biopsy
      forceps, Fogarty balloon catheter, alligator forceps or wire baskets are
      effective.

PMID- 15940437
TI  - Clopidogrel in acute coronary syndrome: when, how much, how long?
AB  - An important part of the therapy management of acute coronary syndrome (ACS)
      consists of antiplatelet drugs. Whereas the administration of acetylsalicylic
      acid (ASA) is well established, the guidelines recommend the additive use of
      clopidogrel in patients with ACS without persisting ST-elevation. Clopidogrel
      should be added to ASA as soon as possible in patients with a non-invasive
      treatment strategy and continued for more than 1 month (class 1A) and up to 9
      months (class 1B). In patients for whom a percutaneous coronary intervention
      (PCI) is planned, an additional loading-dose of 300 mg clopidogrel should be
      given on top of ASA (100 mg). These recommendations are based on data recently
      published in the CURE and CREDO trials, which however should be critically
      discussed: In these trials, an absolute risk reduction of only 2% could be
      documented by additive use of clopidogrel. The combined endpoint of
      cardiovascular death, myocardial infarction and stroke is significantly reduced,
      but there was no improvement taken the individual endpoints alone. In additional,
      the data for duration of clopidogrel therapy were determined by taken the mean
      follow-up of these studies. The efficacy of the dual antiplatelet therapy should
      be discussed in the context of an increased frequency of major bleedings (in
      total 1%) and should be considered against a reasonable cost effective
      background. An adequate therapy with clopidogrel in patients presenting ACS
      should be confirmed by further trials. Until more detailed data are available,
      the guideline recommendations should be implemented based on of patient's
      individual risk.

PMID- 15940438
TI  - Biocompatibility screening in cardiovascular implants.
AB  - BACKGROUND: Interest in information on biocompatibility of implants is
      increasing. The purpose of this paper is to discuss methods and results of
      pathological biocompatibility screening of explanted cardiovascular implants.
      METHODS: Use of standard histology after embedding in paraffin is limited since
      metallic implants have to be removed during workup with disruption of the
      specimen. Alternatively, tissue blocks containing an implant can be embedded in
      methylmethacrylate or hydroxyethylmethacrylate and processed by sectioning with a
      diamond cutter and grinding, thus leaving the implant in situ and saving the
      tissue/implant interface for detection of local inflammatory reactions. Another
      important aspect of evaluation is the progress of thrombus organisation after
      initial fibrin clotting on the metal surface or in the inner part of occlusion
      devices. New methacrylate resins and embedding techniques allow for specific
      immunohistochemical staining of the specimen thus enabling characterisation of
      tissues surrounding the implant. Information on endothelialisation of the
      vascular surface of the implant can be obtained by means of immunohistochemistry
      or by scanning electron microscopy. RESULTS: Illustrating the use of these
      technologies, we demonstrate findings in tissue specimens from animal studies
      with different types of devices (i.e. stents, occlusion devices). We present
      corresponding findings in human specimens with implants that were removed during
      corrective surgery for congenital heart defects. Early endothelialisation of the
      vascular surface was seen after implantation in all types of devices. Cells
      within occlusion devices could be characterised histologically and
      immunohistochemically as fibromuscular cells as seen in intimal hyperplasia after
      stent implantation. Inflammatory implant-host reactions ranged from mild to
      moderate (medical grade stainless steel, nitinol) to severe
      (polytetrafluoroethylene [PTFE]). CONCLUSIONS: With an optimal work-up of
      cardiovascular implants, ingrowth and endothelialisation as well as inflammatory
      reactions in the surrounding tissue can be assessed. This information allows
      evaluation of individual tissue reactions to the implant and may serve as
      valuable basis for optimisation of biocompatibility by implant modification.

PMID- 15940439
TI  - Incications and complications of invasive diagnostic procedures and percutaneous
      coronary interventions in the year 2003. Results of the quality control registry
      of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausarzte (ALKK).
AB  - BACKGROUND: The ALKK registry contains about 20% of the invasive and
      interventional cardiological procedures performed in Germany. METHODS: In 2003 a
      total of 82,282 consecutive diagnostic invasive and 30,689 interventional
      procedures from 75 hospitals were centrally collected and analyzed. RESULTS: The
      main indication for an invasive diagnostic procedure was coronary artery disease
      in 92.5% of cases, myocardial disease in 1.6%, impaired left ventricular function
      in 4.0%, valve disease in 4% and other indications in 1.9%. An acute coronary
      syndrome was present in 25% of the patients. The rate of severe complications in
      patients with a lone diagnostic invasive procedure was low (<0.5%). The
      indication for percutaneous coronary intervention (n=30,689) was stable angina in
      44.1%, ST elevation myocardial infarction in 22.3%, non ST elevation myocardial
      infarction in 14.8%, unstable angina in 10.0%, silent ischemia in 2.2%,
      prognostic in 5.2% of patients. The majority of interventions were performed
      directly after the diagnostic procedure (n=23,887=78.6%). The intervention was
      successful in 94.6% of cases. Stent implantation was performed in 77.2%, with 1
      stent in 88.4%, two stents in 7.6% and 3 or more stents in 3.3%. A drug-eluting
      stent was implanted in 3.6% of the cases. The complication rate after PCI was
      influenced by the indication for the intervention. The in-hospital mortality in
      patients with cardiogenic shock was 33%, while in patients with stable angina,
      silent ischemia and prognostic indication only 0.2% died. CONCLUSION: There is an
      increase of invasive diagnostic and interventional procedures in patients with
      acute coronary syndromes, with 47% of PCIs performed in these patient. PCIs were
      performed in 75% of the cases directly after the diagnostic procedure. The rate
      of stent implantation seems to have reached a plateau at around 80%, while drug
      eluting stents were implanted only in a minority of cases. The complication rate
      is mainly dependent on the clinical presentation of the patients and the
      indication for PCI.

PMID- 15940440
TI  - Reference values of NT-proBNP serum concentrations in the umbilical cord blood
      and in healthy neonates and children.
AB  - BACKGROUND: N-terminal brain natriuretic peptide (NT-proBNP) is a neurohormonal
      substance secreted mainly by the cardiac myocytes of the left ventricle and to a
      less degree of the left atrium. The releasing mechanism is induced by an
      increased wall stress on the base of volume or pressure load of the ventricle.
      The physiologic actions of BNP are prohibition of the sympathetic activity,
      vasodilatation, natriuresis, diureses and inhibition of the renin-angiotensin
      system. Because of its high sensitivity and specifity in relation to the left
      ventricular incompetence, BNP as well as NTproBNP are well accepted markers of
      ventricular dysfunction. It was the aim of the study to establish reference
      values of NT-proBNP serum concentrations throughout childhood, in particular in
      the newborn age group. METHODS: In a cross sectional study, serum NT-proBNP
      concentrations were measured by an ElectroChemiLuminescenceImmunoAssay ("ECLIA"
      Roche) in the umbilical cord blood of 62 healthy full-term neonates and in 222
      healthy probands from birth up to the age of 18 years. RESULTS: The concentration
      of NT-proBNP in the cord blood samples ranged from 281 to 2595 pg/ml (mean: 818
      pg/ml). There was a significant increase in the first days of life followed by a
      rapid decrease during the first year and a further gradual decrease throughout
      infancy; beyond the 10(th) year of age normal adult values were approached.
      CONCLUSIONS: The knowledge of the normal range of plasma NT-proBNP levels in
      healthy subjects during childhood serves as a non-invasive marker for
      differentiation of pathologic conditions such as acute myocarditis, hypertrophic
      or dilated cardiomyopathy, tachyarrhythmias and pulmonary hypertension.

PMID- 15940441
TI  - Angiographic and clinical outcome for the treatment of in-stent restenosis with
      sirolimus-eluting stent compared to vascular brachytherapy.
AB  - BACKGROUND: With the use of coronary stents for the treatment of coronary artery
      disease, in-stent restenosis became a major clinical problem. In this non
      randomized study, we examined the use of stent-based delivery of sirolimus
      (rapamycin) for the treatment of in-stent restenosis in comparison to
      intracoronary beta-brachytherapy, regarding the clinical effectiveness and the
      angiographic results for the treatment of in-stent restenosis after 6-9 months.
      METHODS AND RESULTS: Between July 2001 and May 2002, 28 patients (65+/-11 years)
      with instent restenosis were treated with intracoronary brachytherapy.
      Consecutively, between May 2002 and April 2003, 28 patients (65+/-10 years) with
      in-stent restenosis were treated with the implantation of a sirolimus-eluting
      stent (SES). Patients with in-stent restenosis treated by implantation of a SES
      had significantly lower incidence of in-stent restenosis (1/28 (3.6%) vs 10/28
      (36%); p=0.007) and insegment restenosis (4/28 (14%) vs 14/28 (50%); p=0.013)
      compared to patients treated with brachytherapy. Target lesion and target vessel
      revascularization rate tended to be lower in the SES group (14 vs 25%) but did
      not yet reach statistical significance. One patient died in the group treated by
      implantation of a SES eight months after stenting, one patient suffered from
      myocardial infarction due to a subtotal in-stent restenosis after brachytherapy.
      Two patients after brachytherapy underwent surgical revascularization due to
      recurrent in-stent restenosis similar to the patient with in-stent restenosis
      after SES implantation. CONCLUSION: In this study we show the feasibility and
      safety of the treatment of in-stent restenosis by implantation of sirolimus
      eluting stents and demonstrate a lower incidence of recurrent in-stent restenosis
      as well as lower late luminal loss compared to treatment by intravascular
      brachytherapy.

PMID- 15940442
TI  - Malignant oesophago-pleuro-pericardial fistula in a patient with oesophageal
      carcinoma.
AB  - Pericardial and cardiac fistulae secondary to oesophageal or gastric tumours are
      a rare complication. We report about a 50-year-old male patient with a 10-month
      history of distal oesophageal carcinoma with lung and liver metastases who was
      referred to our hospital after 6 cycles of palliative chemotherapy at the
      beginning of March 2004. The patient presented with dysphagia, dyspnea,
      tachycardia, and hypotension. Purulent pericardial and bilateral pleural effusion
      was diagnosed, and the patient was treated with antibiotics, repeated
      pleurocentesis and pericardial drainage with daily polihexanide lavage.
      Oesophagogastroduodenoscopy, Peritrast swallow and computed tomographic scans of
      chest revealed a malignant oesophago-pleuro-pericardial fistula. A total of three
      coated, expandable metal stents were inserted into the oesophagus, which sealed
      successfully the fistula. Unfortunately, the patient succumbed to his carcinoma
      three months later.

PMID- 15940443
TI  - Implantation of an "extracardiac" internal cardioverter defibrillator in a 6
      month-old infant.
AB  - In infants and small children, ICD implantation is a challenge due to technical
      limitations and a significant number of complications. This report describes ICD
      implantation in a 6-month-old infant (body weight 5.5 kg). A completely
      extracardiac defibrillation system was implanted using a transvenous lead
      subcutaneously in the back below the left scapula as the defibrillation electrode
      and an active-can device in the right upper abdomen. Defibrillation threshold of
      implantation was < or =10 J. During the follow-up of 3 months, 8 adequate ICD
      discharges were noted. The technique described seems feasible to facilitate ICD
      implantation in small infants.

PMID- 15940444
TI  - [Horst Schmutzler, 80 years old].

PMID- 15940447
TI  - Wilhelm Fresenius 1913-2004.

PMID- 15940448
TI  - Integrating functional components into capillary electrophoresis systems using
      liquid-core waveguides.

PMID- 15940449
TI  - Photoacoustic spectroscopy for process analysis.
AB  - Photoacoustic spectroscopy (PAS) is based on the absorption of electromagnetic
      radiation by analyte molecules. The absorbed energy is measured by detecting
      pressure fluctuations in the form of sound waves or shock pulses. In contrast to
      conventional absorption spectroscopy (such as UV/Vis spectroscopy), PAS allows
      the determination of absorption coefficients over several orders of magnitude,
      even in opaque and strongly scattering samples. Small absorption coefficients,
      such as those encountered during trace gas monitoring, can be detected with cells
      with relatively short pathlengths. Furthermore, PA techniques allow absorption
      spectra of solid samples (including powders, chips or large objects) to be
      determined, and they permit depth profiling of layered systems. These features
      mean that PAS can be used for on-line monitoring in technical processes without
      the need for sample preparation and to perform depth-resolved characterization of
      industrial products. This article gives an overview on PA excitation and
      detection schemes employed in analytical chemistry, and reviews applications of
      PAS in process analytical technology and characterization of industrial products.

PMID- 15940450
TI  - Three-way partial least-squares regression for the simultaneous kinetic-enzymatic
      determination of xanthine and hypoxanthine in human urine.
AB  - The performance of three-way principal component analysis and three-way partial
      least-squares regression when applied to a complex kinetic-enzymatic system is
      studied, in order to investigate the analytical potential of the combined use of
      these chemometric technologies for non-selective enzymatic systems. A enzymatic
      kinetic procedure for the simultaneous determination of hypoxanthine and xanthine
      in spiked samples of human urine is proposed. The chemical system involves two
      consecutive reactions catalyzed by xanthine oxidase (EC 1.17.3.2). This enzyme
      catalyzes the oxidation of hypoxanthine, first to xanthine and then to uric acid,
      a competitive inhibitor of the reactions. The influence of uric acid during
      quantitative determination was considered in the design of the calibration set.
      The sample and enzyme solution were mixed in a stopped-flow module and the
      reaction was monitored using a diode array spectrophotometer. The recorded data
      have an intrinsical three-component structure (samples, time and wavelength).
      This data array was studied via three-way principal component analysis and was
      modeled for quantitative purposes using a three-way partial least-squares
      calibration procedure. Results are compared with those obtained by applying
      classical bilinear PLS to the previously unfolded data matrix.

PMID- 15940451
TI  - Optical interrogation of molecularly imprinted polymers and development of MIP
      sensors: a review.
AB  - This article reviews the progress and developments achieved in the past five
      years (2000-2005) in the application of optical analytical techniques to the
      evaluation of molecularly imprinted polymer (MIP) characteristics. The MIP
      binding efficiency, recognition processes and selectivity have been intensively
      studied by optical means due to the general high sensitivity and simplicity of
      the utilisation of optical techniques. In addition, recent progress in the
      covalent linkage of MIPs to optical transducers has allowed for the realisation
      of highly efficient and robust optical MIP-based molecular recognition sensors.
      The review provides insight into the various approaches to the optical
      interrogation of MIPs, and is organised according to the type of optical
      technique employed (fluorescence, UV/Vis and infrared spectroscopy, surface
      plasmon resonance, chemiluminescence, refractive interference spectroscopy and
      Raman scattering) and the detailed strategies applied. The review also covers the
      recent progress achieved in the area of optical sensors based on MIPs.

PMID- 15940452
TI  - Investigation of a cylindrical chemosorptive denuder for sampling and phase
      separation of toluene diisocyanate aerosols.
AB  - A cylindrical chemosorptive denuder in series with a glass fibre filter has been
      evaluated for sampling toluene diisocyanate (TDI) aerosols. The sampler is
      designed for measuring personal exposure to diisocyanates. Several denuder
      coatings and derivatising reagents were investigated. Dimethylpolysiloxane (SE
      30) and 5% phenyl dimethylpolysiloxane (SE-54) with either dibutylamine (DBA) or
      dipentylamine (DPeA) as derivatising reagents yielded the lowest vapour
      breakthrough (the amount (%) of the vapour that passes through the denuder),
      close to values predicted by theory. Immobilisation of the SE-30 denuder coating
      by in-situ cross-linking yielded comparable results. With an SE-30/DBA-coated
      denuder operating within an airflow range of 100-500 mL min(-1), the phase
      separation was shown to be consistent with theoretical predictions derived by use
      of the Gormley-Kennedy equation. This provides a means of calculating the vapour
      breakthrough and correcting experimentally obtained values with regard to vapour
      particulate phase distribution, suggesting that the denuder can provide accurate
      phase-distribution measurements. The SE-30/DBA denuder can be used over a
      concentration range spanning nearly six orders of magnitude. Its capacity is
      sufficient to perform 15-min exposure measurements of a TDI aerosol with air
      concentrations as high as 1,700 microg m(-3), 40 times higher than the Swedish
      occupational exposure limit (OEL). At the other end of the range, the estimated
      limit of detection (LOD) was less than 2 ng m(-3) for both the vapour and the
      aerosol phases when LC-ESI-MS-MS was used for chemical analysis.

PMID- 15940453
TI  - Instruction in bioanalytical chemistry.

PMID- 15940454
TI  - Quantitative determination of organochlorine pesticides in sewage sludges using
      soxtec, soxhlet and pressurized liquid extractions and ion trap mass-mass
      spectrometric detection.
AB  - A new analytical method is described for the determination of organochlorine
      pesticides (OCPs) in sewage sludges using GC-ion trap-MS-MS. In this work, 16
      organo-chlorine pesticides (OCPs) listed by the US Environmental Protection
      Agency (US EPA) as priority pollutants were separated and quantified. Sludge
      samples from three of Kuwait's wastewater treatment plants (WWTPs) were analyzed
      for organochlorine pesticides (OCPs). Spiked sludge samples were extracted with a
      mixture of (1:1 v/v) dichloromethane (DCM)/hexane. The extracts were cleaned on a
      silica/aluminum oxide column, then transferred to a gel permeation chromatography
      (GPC) column, before undergoing further silica/aluminum oxide clean-up; the
      presence of OCPs was then confirmed by GC-ion trap-MS-MS. Three extraction
      techniques, soxtec, soxhlet, and pressurized liquid extractions were utilized,
      compared and validated using the spiked sludge samples. The methods were
      validated in term of accuracy (recovery) and precision (RSD). The method recovery
      values varied from 76.1 to 92.9% for the three extraction techniques.

PMID- 15940455
TI  - Determination of ageing time of spirits in oak barrels using a headspace-mass
      spectrometry (HS-MS) electronic nose system and multivariate calibration.
AB  - The aromatic composition of sugar cane spirits and, in general, of alcoholic
      beverages, is mainly influenced by the ageing process in wood barrels. There are
      several factors that affect the quality of the final aged product, but the time
      of the storage in the barrel is perhaps the most important one. Ageing time must
      therefore be controlled in order to detect counterfeits; however, this parameter
      is very difficult to control and, at present, there is no analytical method
      available to determine it. We propose a quantitative method for determining the
      ageing time of sugar cane spirits in oak barrels by using an electronic nose
      based on coupling directly a headspace sampler to a mass spectrometer (HS-MS),
      and multivariate calibration. The method developed is simple and provides, in 5
      min, the ageing time of spirits with an accuracy of about 1 month.

PMID- 15940456
TI  - Use of 1,5-bis(di-2-pyridyl)methylene thiocarbohydrazide immobilized on silica
      gel for automated preconcentration and selective determination of antimony(III)
      by flow-injection electrothermal atomic absorption spectrometry.
AB  - Selective sorption of Sb(III) on a microcolumn packed with 1,5-bis(di-2
      pyridyl)methylene thiocarbohydrazide immobilized on silica gel (DPTH-gel) has
      been used for determination of Sb(III). A flow-injection system comprising a
      microcolumn connected to the tip of the autosampler was used for
      preconcentration. The sorbed antimony was eluted with nitric acid directly into
      the graphite furnace and determined by AAS. The detection limit for antimony
      under the optimum conditions was 0.3 ng mL(-1). This procedure was used for
      determination of antimony in natural water, soil, vegetation, and a certified
      sample of a city waste incineration ash (BCR 176).

PMID- 15940457
TI  - alpha-Glucosidase from a strain of deep-sea Geobacillus: a potential enzyme for
      the biosynthesis of complex carbohydrates.
AB  - An alpha-glucosidase from Geobacillus sp. strain HTA-462, one of the deepest sea
      bacteria isolated from the sediment of the Mariana Trench, was purified to
      homogeneity and estimated to be a 65-kDa protein by SDS-PAGE. At low ion
      strength, the enzyme exists in the homodimeric form (130 kDa). It is a thermo-
      and alkaline-stable enzyme with a half-life of 13.4 h and a maximum hydrolytic
      activity at 60 degrees C and pH 9.0 in 15 mM glycine-NaOH buffer. The enzyme
      exclusively hydrolyzed alpha-1,4-glycosidic linkages of oligosaccharides in an
      exo-type manner. The enzyme had an overwhelming transglycosylation activity and
      glycosylated various non-sugar molecules when maltose was used as a sugar donor.
      It converted maltose to isomaltose. The gene encoding the enzyme was cloned and
      sequenced. The recombinant enzyme could be extracellularly overproduced by
      Bacillus subtilis harboring its gene and preserved the primary properties of the
      native enzyme. Site-directed mutagenesis experiments showed that Asp98 is
      essential for the enzyme activity in addition to Asp199, Asp326, and Glu256.

PMID- 15940458
TI  - The effects of ftsZ mutation on the production of recombinant protein in Bacillus
      subtilis.
AB  - In this paper, the possibility of using a mutation of ftsZ as a pseudo-spore
      mutant is investigated. ftsZ, which is essential for cell division and
      sporulation of Bacillus subtilis, was placed under the spac promoter, which is
      inducible with isopropyl thiogalactose (IPTG). Cell growth of the ftsZ mutant and
      its beta-galactosidase activity under the aprE promoter were compared with the
      wild type. In the presence of 1 mM IPTG, cell growth of the ftsZ mutant was
      almost the same as that of the wild type and its sporulation frequency was
      slightly lower than that of the wild type. However, under uninduced conditions,
      cell growth of ftsZ mutant was severely impaired. When induced with 0.2 mM IPTG,
      the ftsZ mutant showed about 13 times higher beta-galactosidase activity than the
      wild type. When the ftsZ mutant was used for secretory production of subtilisin,
      only three times higher extracellular subtilisin activity was measured, compared
      with the wild type. By real-time PCR investigation, it was revealed that the ftsZ
      mutant intracellular mRNA level for subtilisin was more than 16 times higher,
      compared with the wild type. However, it appears that the secretion pathway is
      somewhat damaged in the ftsZ mutant. These results suggest that the cell division
      mutant can also be used like a sporulation mutant to produce recombinant
      proteins, with a precise control of cell growth and induction.

PMID- 15940459
TI  - Subcompartmental intra abdominal hypertension.

PMID- 15940460
TI  - Erythromycin dose of 70 mg accelerates gastric emptying as effectively as 200 mg
      in the critically ill.
AB  - OBJECTIVE: To compare the effectiveness of 70-mg and 200-mg doses of intravenous
      erythromycin in improving gastric emptying in critically ill patients. DESIGN:
      Gastric emptying was measured on consecutive days; day 1 (pre-treatment), day 2
      (post-treatment) after an intravenous infusion of either 70 or 200 mg
      erythromycin or saline placebo (0.9%), in a randomized double-blind fashion.
      SETTING: Mixed medical/surgical intensive care unit, tertiary referral. PATIENTS
      AND PARTICIPANTS: Thirty-five randomly selected, mechanically ventilated,
      enterally fed critically ill patients (median APACHE II score 19 on admission).
      INTERVENTIONS: On day 2 either 70 or 200 mg erythromycin or saline was
      administered intravenously over 20 min. MEASUREMENTS AND RESULTS: Gastric
      emptying was measured using the [13C]octanoic acid breath test. The gastric
      emptying coefficient (GEC) and half-emptying time (t1/2) were calculated from the
      area under the 13CO2-recovery curve. Pre-treatment gastric emptying measurements
      were similar in all three patient groups. Treatment with both doses of
      erythromycin significantly reduced the gastric t1/2: 70 mg, 98 min (IQR 88-112);
      200 mg, 86 min (75-104); vs. placebo, 122 min (102-190) (p<0.05). The GEC was
      higher with both doses of erythromycin: 70 mg, 3.8 (3.3-4.0); 200 mg, 4.0 (3.6
      4.2); vs. placebo, 2.9 (2.5-3.7) (p<0.05). There was no difference in gastric
      emptying post-treatment between the two doses of erythromycin. The effect of
      erythromycin was greatest in patients with delayed gastric emptying. CONCLUSIONS:
      Treatment with 70 and 200 mg intravenous erythromycin are equally effective in
      accelerating gastric emptying in the critically ill.

PMID- 15940461
TI  - Cuticular wax deposition in growing barley (Hordeum vulgare) leaves commences in
      relation to the point of emergence of epidermal cells from the sheaths of older
      leaves.
AB  - In grasses, leaf cells divide and expand within the sheaths of older leaves,
      where the micro-environment differs from the open atmosphere. By the time
      epidermal cells are displaced into the atmosphere, they must have a functional
      cuticle to minimize uncontrolled water loss. In the present study, gas
      chromatography and scanning electron microscopy were used to follow cuticular wax
      deposition along the growing leaf three of barley (Hordeum vulgare L.). 1
      Hexacosanol (C(26) alcohol) comprised more than 75% of extractable cuticular wax
      and was used as a marker for wax deposition. There was no detectable wax along
      the first 20 mm from the point of leaf insertion. Deposition started within the
      distal portion of the elongation zone (23-45 mm) and continued beyond the point
      of leaf emergence from the sheath of leaf two. The region where wax deposition
      commenced shifted towards more proximal (basal) positions when the point of leaf
      emergence was lowered by stripping back part of the sheath. When relative
      humidity in the shoot environment was elevated from 70% (standard growth
      conditions) to 92-96% for up to 4 days prior to analysis, wax deposition did not
      change significantly. The results show that cuticular waxes are deposited along
      the growing grass leaf independent of cell age or developmental stage. Instead,
      the reference point for wax deposition appears to be the point of emergence of
      cells into the atmosphere. The possibility of changes in relative humidity
      between enclosed and emerged leaf regions triggering wax deposition is discussed.

PMID- 15940462
TI  - Sequence evolution and sex-specific expression patterns of the C class floral
      identity gene, SpAGAMOUS, in dioecious Spinacia oleracea L.
AB  - Development in dioecious cultivated spinach, Spinacia oleracea, is distinguished
      by the absence of alternative reproductive organ primordia in male and female
      flowers. Given the highly derived floral developmental program in spinach, we
      wished to characterize a spinach C class floral identity gene and to determine
      the patterns of sequence evolution as well as compare the spatial and temporal
      expression patterns with those of AGAMOUS. The isolated cDNA sequence clusters
      phylogenetically within the AGAMOUS/FARINELLI C class clade. In comparison with
      the SLM1 sequence from the related Silene latifolia, amino acid replacements are
      highly conservative and non-randomly distributed, being predominantly found in
      hinge regions or on exposed surfaces of helices. The spinach gene (SpAGAMOUS)
      appears to be exclusively expressed in reproductive tissues and not in vegetative
      organs. Initial expression of SpAGAMOUS is similar in male and female floral
      primordia. However, upon initiation of the first whorl organs, SpAGAMOUS becomes
      restricted to meristemic regions from which the reproductive primordia will
      develop. This results in an early gender-specific pattern. Thus, the spinach C
      class gene is differentially expressed prior to reproductive organ development
      and is, at least, correlated with, if not directly involved in, the sexual
      dimorphism in spinach.

PMID- 15940463
TI  - The genome sequence of black cottonwood (Populus trichocarpa) reveals 18
      conserved cellulose synthase (CesA) genes.
AB  - The genome sequence of Populus trichocarpa was screened for genes encoding
      cellulose synthases by using full-length cDNA sequences and ESTs previously
      identified in the tissue specific cDNA libraries of other poplars. The data
      obtained revealed 18 distinct CesA gene sequences in P. trichocarpa. The
      identified genes were grouped in seven gene pairs, one group of three sequences
      and one single gene. Evidence from gene expression studies of hybrid aspen
      suggests that both copies of at least one pair, CesA3-1 and CesA3-2, are actively
      transcribed. No sequences corresponding to the gene pair, CesA6-1 and CesA6-2,
      were found in Arabidopsis or hybrid aspen, while one homologous gene has been
      identified in the rice genome and an active transcript in Populus tremuloides. A
      phylogenetic analysis suggests that the CesA genes previously associated with
      secondary cell wall synthesis originate from a single ancestor gene and group in
      three distinct subgroups. The newly identified copies of CesA genes in P.
      trichocarpa give rise to a number of new questions concerning the mechanism of
      cellulose synthesis in trees.

PMID- 15940464
TI  - A methionine synthase homolog is associated with secretory vesicles in tobacco
      pollen tubes.
AB  - Seven isoforms of 85 kDa polypeptides (p85) were identified as methionine
      synthase (MetE) homologs by partial aminoacid sequencing in tobacco pollen tube
      extracts. Immunocytochemistry data showed a localization of the antigen on the
      surface of tip-focussed post-Golgi secretory vesicles (SVs), that appear to be
      partially associated with microtubules (Mts). The chemical dissection of pollen
      tube high speed supernatant (HSS) showed that two distinct pools of MetE are
      present in pollen tubes, one being the more acidic isoforms sedimenting at 15S
      and the remaining at 4S after zonal centrifugation through a sucrose density
      gradient. The identification of the MetE within the pollen tube and its possible
      participation as methyl donor in a wide range of metabolic reactions, makes it a
      good subject for studies on pollen tube growth regulation.

PMID- 15940465
TI  - Gene structure and molecular analysis of the laccase-like multicopper oxidase
      (LMCO) gene family in Arabidopsis thaliana.
AB  - Completed genome sequences have made it clear that multicopper oxidases related
      to laccase are widely distributed as multigene families in higher plants. Laccase
      like multicopper oxidase (LMCO) sequences culled from GenBank and the Arabidopsis
      thaliana genome, as well as those from several newly cloned genes, were used to
      construct a gene phylogeny that clearly divided plant LMCOs into six distinct
      classes, at least three of which predate the evolutionary divergence of
      angiosperms and gymnosperms. Alignments of the predicted amino acid sequences
      highlighted regions of variable sequence flanked by the highly conserved copper
      binding domains that characterize members of this enzyme family. All of the
      predicted proteins contained apparent signal sequences. The expression of 13 of
      the 17 LMCO genes in A. thaliana was assessed in different tissues at various
      stages of development using RT-PCR. A diversity of expression patterns was
      demonstrated with some genes being expressed in a constitutive fashion, while
      others were only expressed in specific tissues at a particular stage of
      development. Only a few of the LMCO genes were expressed in a pattern that could
      be considered consistent with a major role for these enzymes in lignin
      deposition. These results are discussed in the context of other potential
      physiological functions for plant LMCOs, such as iron metabolism and wound
      healing.

PMID- 15940466
TI  - Bleeding diathesis in a child with normal screening tests: think about
      fibrinolysis.

PMID- 15940467
TI  - Intra- and inter-specific variations in the copy number of two types of
      retrotransposons from the ectomycorrhizal basidiomycete Tricholoma matsutake.
AB  - To explore intra- and inter-specific variations of the ectomycorrhizal
      basidiomycete Tricholoma matsutake that produces the fruit body "matsutake", we
      carried out real-time PCR analysis based on two types of retrotransposons, one
      designated marY1, which resembles a retrovirus carrying the long terminal repeat
      (LTR) and the other marY2N, which resembles mRNA carrying the polyadenylated
      tail. Calculation based on the average genome size of homobasidiomycetes (34 Mbp)
      shows that ca. 5.5% of the total genome of T. matsutake isolated from Asia is
      made up of these retrotransposons, whereas they occupy ca. 1.4% in the isolates
      from Morocco, ca. 0.8% in isolates from Mexico, and ca. 0.5% in Tricholoma
      magnivelare, the species which produces "American matsutake". Other Tricholoma
      spp. that produce fruit bodies similar to those of T. matsutake, such as T.
      bakamatsutake, T. fulvocastaneum, and T. robustum, carry them in the region less
      than 0.05% of their total genome. Copy number of LTR of marY1 is consistently and
      markedly higher than that of the coding regions of marY1 and marY2N. Data suggest
      that retrotransposons are deeply involved in evolution of the ectomycorrhizal
      symbiont.

PMID- 15940468
TI  - Impaired non-esterified fatty acid suppression to intravenous glucose during late
      pregnancy persists postpartum in gestational diabetes: a dominant role for
      decreased insulin secretion rather than insulin resistance.
AB  - AIMS/HYPOTHESIS: Non-esterified fatty acids are implicated in the pathogenesis of
      gestational (GDM) and type 2 diabetes. We examined the relationship between NEFA
      dynamics, insulin resistance and beta cell dysfunction in women with GDM in late
      pregnancy and postpartum. METHODS: A total of 19 Caucasian women with GDM and 19
      healthy pregnant women matched for BMI and age underwent an IVGTT in the third
      trimester and 4 months postpartum, deriving values for insulin sensitivity (SI),
      insulin secretion (AIRg) and disposition index (DI). NEFA levels were measured
      serially. RESULTS: In pregnancy, the GDM women had similar SI but reduced AIRg
      and DI compared with control subjects. The GDM group demonstrated significantly
      slower NEFA suppression, which was attributable to the GDM women who required
      insulin during pregnancy (n=7) and who had markedly reduced AIRg and K(NEFA)
      (NEFA disappearance constant) compared with their matched controls. In contrast,
      GDM subjects not requiring insulin (n=12) had similar NEFA suppression curves and
      AIRg to control subjects. Postpartum, GDM subjects demonstrated reduced SI and
      DI. The impaired suppression of NEFA persisted postpartum, but again only in the
      subgroup of GDM subjects who had required insulin during pregnancy. Furthermore,
      K(NEFA) correlated with AIRg and DI in both states, but not with SI.
      CONCLUSIONS/INTERPRETATION: Impaired NEFA suppression occurs in GDM subjects both
      in late pregnancy and postpartum in response to IVGTT-induced endogenous insulin
      secretion. The impaired NEFA suppression is present in GDM women with the most
      severe beta cell dysfunction (who had required insulin during pregnancy) and is
      related to their insulin secretory dysfunction rather than their reduced SI.

PMID- 15940469
TI  - Effect of low-level lifetime exposure to cadmium on calciotropic hormones in aged
      female rats.
AB  - The effect of low-level lifetime exposure to cadmium (Cd) on calciotropic
      hormones and the possible association between the Cd-induced disorders in bone
      metabolism and these hormones were investigated on a female rat model of human
      environmental exposure in areas unpolluted by this metal. For this purpose, the
      concentrations of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D
      (1,25(OH)(2)D), calcitonin (CT) and parathormone (PTH) were measured in the serum
      of control and Cd-exposed (1 mg Cd/l in drinking water for 24 months) female
      rats. Calcium (Ca) and inorganic phosphorus (P(i)) serum concentrations, renal
      tubular reabsorption of Ca (TRCa) and phosphate (TRP) and the glomerular
      filtration rate (GFR) were estimated as well. Moreover, 1,25(OH)(2)D,
      metallothionein (MT) and Cd were determined in the kidney. The exposure to Cd led
      to a decrease in the serum concentrations of 25OHD and 1,25(OH)(2)D (by 50 and
      31%, respectively) and the concentration of 1,25(OH)(2)D in the kidney
      mitochondrial fraction (by 55%). The serum concentrations of CT and PTH increased
      (5.2-fold and by 29%, respectively) and those of Ca and P(i) were unchanged,
      whereas the TRCa, TRP and GFR decreased due to the exposure to Cd. The results
      give evidence that the low lifetime exposure to Cd disturbs the metabolism of
      calciotropic hormones and damages the reabsorptive and filtrative function of the
      kidney in aged female rats. Numerous correlations noted between calciotropic
      hormones and the indices of kidney function, and indices of bone turnover and
      bone mineral status (bone mineral content and density) of these females indicate
      a relationship between these hormones and the kidney functional status and bone
      metabolism. The results of the present study together with our previous findings
      on the bone status in the experimental model allow for the conclusion that the
      low lifetime exposure to Cd by affecting the metabolism and proper function of
      calciotropic hormones may contribute to the advancement of bone damage at the
      elderly.

PMID- 15940470
TI  - Use of the dog as non-rodent test species in the safety testing schedule
      associated with the registration of crop and plant protection products
      (pesticides): present status.
AB  - The results from a survey of the expert information that is publicly accessible
      on the use of the dog as test species during the regulatory evaluation of
      agricultural chemicals and pesticides are reported. Methods that are being used
      or considered in order to reduce the number of dogs used for this purpose are
      described. Regulatory evaluation aims at establishing threshold values for safe
      human exposure; it is based on no-observed-adverse-effect levels (NOELs)
      determined in animal studies. Current regulations require testing in two species,
      a rodent species (usually rat or mouse), and a non-rodent species (usually the
      dog). Subchronic (90-day) and chronic (12-month) repeated-dose feeding studies
      must be routinely conducted in dogs. This report first focuses on the results
      from a retrospective study analysing data on 216 pesticides kept on record by the
      Bundesinstitut fur Risikobewertung, BfR (German Federal Institute for Risk
      Assessment), the competent regulatory authority in Germany. The study was
      sponsored and coordinated by SET, the German Foundation for the Promotion of
      Research on Replacement and Complementary Methods to Reduce Animal Testing
      (Stiftung zur Forderung der Erforschung von Ersatz-und Erganzungsmethoden zur
      Einschrankung von Tierversuchen, Mainz) and conducted by the BfR. Since the data
      submitted for registration of a product is the property of the manufacturer, the
      study could only proceed with the collaboration of the German Association of
      Manufacturers of Agricultural Chemicals (Industrieverband Agrar, IVA). To ensure
      confidentiality, designated codes were used instead of the compounds' proper
      names when the study was published. The results support two major conclusions.
      The use of the dog for the testing of pesticides is indeed necessary because the
      dog has proved to be the most sensitive species for about 15% of the compounds
      examined. However, chronic studies are only of limited value since they only
      provide essential information that cannot be obtained in sub-chronic studies in
      about 5% of cases. These conclusions are supported by several retrospective
      analyses using data on pharmaceutical drugs carried out in the context of the
      International Conference on Harmonisation of Technical Requirements for the
      Registration of Pharmaceuticals for Human Use (ICH). Over 90% of drugs elicited
      no toxic symptoms in 12-month studies in dogs in addition to those that had been
      recorded previously in studies conducted for 90 or 180 days in dogs and rats.
      Another approach comparing the results from pre-clinical animal studies with
      clinical studies noted that animal studies predicted about 70% of the effects
      observed in volunteers, and in about 94% of cases the effects occurred in animal
      studies lasting not more than one month. Furthermore, the report summarises the
      current methods under consideration that could refine or reduce the use of dogs
      in toxicity testing: industrial data sharing and harmonisation of guidelines, in
      vitro methods, human studies, computational prediction models, and integrated
      testing approaches. The integrated Agricultural Chemicals Safety Assessment
      (ACSA) testing scheme, which is currently being developed in an international
      project initiated by the International Life Sciences Institute (ILSI, USA), is of
      particular relevance, since an ambitious attempt is being made to design a new
      comprehensive test framework incorporating modern scientific approaches and
      covering most aspects of current regulatory testing requirements. The ACSA
      project has access to the pesticide database of the US EPA's Office of Pesticide
      Programs (OPP). Preliminary results have confirmed the two major conclusions from
      the joint SET/BfR study conducted in Germany. Taking these results into account,
      it is recommended that the regulatory requirement for 12-month studies to be
      routinely carried out in dogs should be abandoned. While 90-day studies should be
      conducted in both rats and dogs, chronic studies should only take place in rats.
      If the dog is more sensitive than the rat in the 90-day study, an additional
      safety factor to the NOEL value obtained in the chronic rat study should be
      applied in order to set the threshold for safe human exposure, instead of
      conducting a 12-month study in dogs. This safety factor may be calculated from
      chronic NOEL data available in several pesticide databases. Chronic tests using
      dogs would then only be required if the test compound belongs to a new class of
      chemicals that has never been tested before. Thus, the report concludes that,
      according to current scientific knowledge, the routine 12-month studies in dogs
      are no longer required for agricultural chemicals and pesticides, and
      international regulations should be changed accordingly. Active international
      support of such measures is welcomed, from both an economical and an animal
      welfare perspective.

PMID- 15940471
TI  - Dose-dependent liver regeneration in chloroform, trichloroethylene and allyl
      alcohol ternary mixture hepatotoxicity in rats.
AB  - The present study was designed to examine the hypothesis that liver tissue repair
      induced after exposure to chloroform (CF) + trichloroethylene (TCE) + allyl
      alcohol (AA) ternary mixture (TM) is dose-dependent similar to that elicited by
      exposure to these compounds individually. Male Sprague Dawley (S-D) rats (250-300
      g) were administered with fivefold dose range of CF (74-370 mg/kg, ip), and TCE
      (250-1250 mg/kg, ip) in corn oil and sevenfold dose range of AA (5-35 mg/kg, ip)
      in distilled water. Liver injury was assessed by plasma alanine amino transferase
      (ALT) activity and liver tissue repair was measured by (3) H-thymidine
      incorporation into hepatonuclear DNA. Blood and liver levels of parent compounds
      and two major metabolites of TCE [trichloroacetic acid (TCA) and trichloroethanol
      (TCOH)] were quantified by gas chromatography. Blood and liver CF and AA levels
      after TM were similar to CF alone or AA alone, respectively. However, the TCE
      levels in blood and liver were substantially decreased after TM in a dose
      dependent fashion compared to TCE alone. Decreased plasma and liver TCE levels
      were consistent with decreased production of metabolites and elevated urinary
      excretion of TCE. The antagonistic interaction resulted in lower liver injury
      than the summation of injury caused by the individual components at all three
      dose levels. On the other hand, tissue repair showed a dose-response leading to
      regression of injury. Although the liver injury was lower and progression was
      contained by timely tissue repair, 50% mortality occurred only with the high dose
      combination, which is several fold higher than environmental levels. The
      mortality could be due to the central nervous system toxicity. These findings
      suggest that exposure to TM results in lower initial liver injury owing to higher
      elimination of TCE, and the compensatory liver tissue repair stimulated in a dose
      dependent manner mitigates progression of injury after exposure to TM.

PMID- 15940472
TI  - Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on
      cyclosporine A-induced nephrotoxicity in rats.
AB  - The aim of this study was to analyze the effect of streptozotocin (STZ)-induced
      diabetic state and the insulin-like acting, vanadyl sulphate (VS) on cyclosporine
      A (CyA) related nephrotoxicity in rats. Male Wistar rats were divided into six
      groups, of 12 animals each: The control, diabetic rats and diabetic rats whose
      drinking VS in the drinking water in a concentration of 1 mg/ml. Another three
      similarly treated groups were injected intra-peritoneally (ip) with CyA in a dose
      of 25 mg/kg/day for ten doses, 10 days after diabetic induction by using a single
      dose of STZ of 65 mg/kg. Rats were sacrificed 48 h after the last CyA dose and
      serum as well as kidneys were isolated and analyzed. Treatment with CyA to
      control normoglycemic rats resulted in significant increases in kidney weight,
      serum creatinine, urea nitrogen, cholesterol and triglycerides (TG) levels. Also,
      the kidney tissue of CyA-treated control animals showed significant increases in
      total nitrate/nitrite (NO(x)) concentration and malondialdehyde (MDA) production
      level as well as depletion of glutathione (GSH) content and glutathione
      peroxidase (GSH-P(x)) activity level. Histopathologic evaluation of CyA-treated
      control rats revealed tubular atrophy, hyaline casts and focal tubular necrosis.
      However, treatment of diabetic rats with CyA showed significant reduction in
      serum creatinine and elevation in TG level as well as reductions in the kidney
      NO(x) concentration and MDA production level and increase in GSH concentration
      compared to CyA-treated control rats. Moreover, histopathology of the kidney of
      CyA-treated diabetics showed typical changes of the diabetic controls revealing
      glomerular hypertrophy and tubular dilation. On the other hand, treatment with
      CyA to those diabetic animals administered VS in the drinking water resulted in
      exacerbation of renal dysfunction, manifested by significant increases in serum
      indices of nephrotoxicity, cholesterol, TG and bilirubin levels. Also, VS
      administration to CyA-treated diabetics showed significant increase in kidney
      NO(x) concentration compared to those CyA-treated diabetics drinking plain tap
      water, and to a level significantly lower than those CyA-treated controls.
      Histopathologically, kidney of CyA/VS-treated diabetic showed marked CyA related
      changes. In conclusion, STZ-induced diabetes might provide partial protection
      against CyA-induced renal dysfunction. Also, treatment of hyperglycemia with VS
      might exacerbate CyA related nephrotoxicity.

PMID- 15940473
TI  - Hepatotoxic and nephrotoxic effects of cadmium in the frog Rana ridibunda.
AB  - Histological and histochemical alterations in the liver and kidneys of the frog
      Rana ridibunda, which was exposed to 200 ppm aqueous solutions of cadmium for 4,
      10 and 30 days, respectively were investigated. In both the liver and kidneys,
      essential changes appeared after 10 days' exposure, the maximum changes being
      apparent after 30 days of exposure. In the liver, what was very characteristic
      was an increase in the area occupied by Kupffer cells, with the area in the
      animals exposed to cadmium for 30 days being the largest observed. What was also
      apparent was karyomegaly, polyploidy and infiltration. In addition with regard
      the kidneys, Hyaline Globules (HG) and apoptotic bodies occurred at a higher
      rate. At 30 days' exposure, most of the above changes were enhanced. In
      comparison with 10 days' exposure, fibrosis around the blood vessels and between
      hepatocytes, as well as Proliferating Cell Nuclear Antigen (PCNA) reactivity and
      apoptotic bodies increased lightly in the liver. In the kidneys, the most
      pronounced changes were the increase in numbers of apoptotic bodies, PCNA
      reactivity and hyaline globules. It was concluded that the variability in
      positive reactions for various proteins in the hyaline globules may be an
      indication that these (and possibly other) proteins are synthesized by tumor
      cells, but, most probably, that they may represent liver damage, progressive
      nephropathy, or progressive glomerulonephropathy.

PMID- 15940474
TI  - Inadvertent C2-C3 union after C1-C2 posterior fusion in adults.
AB  - INTRODUCTION: Some authors pointed out that there were more than a few patients
      with inadvertent C2-C3 union after C1-C2 posterior fusion, although few detailed
      studies of C2-C3 union have been reported. The purpose of this study was to
      clarify whether C2-C3 union accelerated adjacent C3-C4 disc degeneration after C1
      C2 posterior fusion and to investigate the related factors for C2-C3 union.
      METHODS: Sixteen patients with rheumatoid arthritis (RA group) (4 males, 12
      females, mean age 60 years, mean follow-up period 4 years and 3 months) and
      fifteen patients without RA (non-RA group) (11 males, 4 females, mean 52 years,
      mean follow-up period 3 years and 10 months) who underwent C1-C2 posterior fusion
      were radiologically assessed. The C2-C3 union was defined as trabecular bone
      formation at C2-C3 interlamina in lateral radiograph. C3-C4 disc height was
      measured to evaluate the disc degeneration. RESULTS: C2-C3 union rate was 56% and
      60% in RA group and non-RA group, respectively. In RA group, postoperative C3-C4
      disc height was lower (Student's t-test, P = 0.029) and the decrease rate of C3
      C4 disc height was higher (Student's t-test, P = 0.015) in patients with C2-C3
      union than in patients without C2-C3 union. In non-RA group, the age at operation
      was older (Student's t-test, P = 0.0007), and the C1-C2 fusion angle (Student's t
      test, P = 0.012) was smaller in patients with C2-C3 union than in patients
      without C2-C3 union. CONCLUSIONS: C2-C3 union after C1-C2 posterior fusion
      occurred in more than half of both groups. Inadvertent C2-C3 union should be
      considered a radiological complication and a potential risk factor due to
      acceleration of C3-C4 disc degeneration in RA.

PMID- 15940476
TI  - Clinical studies in spinal surgery.
AB  - There is a growing interest in applying evidence-based approaches also in
      orthopedic surgery. Despite many challenges to the validity of clinical trials in
      orthopedic surgery, it is possible to conduct well-designed trials in this field
      and to produce clinically important findings and reasonably valid conclusions
      about effectiveness, prognosis and diagnosis in orthopedic surgery. We describe
      the main principles for conducting clinical trials in this field as well as some
      of the most common errors and ways to avoid them.

PMID- 15940475
TI  - Back extensor muscle fatigue in patients with lumbar disc herniation. Pre
      operative and post-operative analysis of electromyography, endurance time and
      subjective factors.
AB  - We investigated back muscle fatigue and endurance in patients with lumbar disc
      herniation before and after surgery, and established the degree of association
      between perceived fatigue and objectively measured fatigue. Additionally, the
      relationships between muscle fatigue and endurance time on the one hand, and
      activity, participation, self-efficacy and health on the other, were investigated
      to clarify the grades of association between these factors. Forty-three
      consecutive patients with lumbar disc herniation were tested before surgery and 4
      weeks after surgery. The protocol comprised an isometric endurance test (modified
      Sorensen's test) with concomitant measures of electromyography, and Borg ratings
      of pain and fatigue. To measure activity, participation, self-efficacy and
      health, the patients also filled in questionnaires. Results showed a post
      operatively significant improvement in lumbar muscle fatigue expressed as a
      flatter L5 slope for the men. No significant improvement was found for endurance
      times or for Borg ratings. Endurance time correlated with questionnaire answers
      on physical activity, the Roland-Morris, the Oswestry, self-efficacy and some
      items of the SF-36 with correlation coefficients ranging from 0.52 to 0.91. The
      L5 slope correlated with the Roland-Morris, the Oswestry and some items of the SF
      36 only in women with correlation coefficients between 0.53 and 0.77. We conclude
      that the effects of surgery reduced muscle fatigue for the men. There is an
      association between muscle fatigue and endurance with activity limitations,
      participation restrictions, self-efficacy and health in patients undergoing
      surgery for lumbar disc herniation.

PMID- 15940477
TI  - The long-term mechanical integrity of non-reinforced PEEK-OPTIMA polymer for
      demanding spinal applications: experimental and finite-element analysis.
AB  - Polyetheretherketone (PEEK) is a novel polymer with potential advantages for its
      use in demanding orthopaedic applications (e.g. intervertebral cages). However,
      the influence of a physiological environment on the mechanical stability of PEEK
      has not been reported. Furthermore, the suitability of the polymer for use in
      highly stressed spinal implants such as intervertebral cages has not been
      investigated. Therefore, a combined experimental and analytical study was
      performed to address these open questions. A quasi-static mechanical compression
      test was performed to compare the initial mechanical properties of PEEK-OPTIMA
      polymer in a dry, room-temperature and in an aqueous, 37 degrees C environment
      (n=10 per group). The creep behaviour of cylindrical PEEK polymer specimens (n=6)
      was measured in a simulated physiological environment at an applied stress level
      of 10 MPa for a loading duration of 2000 hours (12 weeks). To compare the
      biomechanical performance of different intervertebral cage types made from PEEK
      and titanium under complex loading conditions, a three-dimensional finite element
      model of a functional spinal unit was created. The elastic modulus of PEEK
      polymer specimens in a physiological environment was 1.8% lower than that of
      specimens tested at dry, room temperature conditions (P<0.001). The results from
      the creep test showed an average creep strain of less than 0.1% after 2000 hours
      of loading. The finite element analysis demonstrated high strain and stress
      concentrations at the bone/implant interface, emphasizing the importance of cage
      geometry for load distribution. The stress and strain maxima in the implants were
      well below the material strength limits of PEEK. In summary, the experimental
      results verified the mechanical stability of the PEEK-OPTIMA polymer in a
      simulated physiological environment, and over extended loading periods. Finite
      element analysis supported the use of PEEK-OPTIMA for load-bearing intervertebral
      implants.

PMID- 15940478
TI  - Accuracy of the clinical examination to predict radiographic instability of the
      lumbar spine.

PMID- 15940479
TI  - Low back pain in a cohort of 622 Tunisian schoolchildren and adolescents: an
      epidemiological study.
AB  - Low back pain (LBP) in children was considered for many years to be a rare
      condition revealing a serious disease, but in the last two decades,
      epidemiological studies have shown that the prevalence of nonspecific LBP in
      children is high. This study was aimed at analyzing the prevalence, severity,
      consequences and associated factors of LBP in children. A cross-sectional study
      was undertaken in two preparatory schools in the city of Monastir, Tunisia, in
      April 2002. This study included a total of 622 children and adolescents--326
      females and 296 males--with a mean age of 14 years (range: 11-19 years). They
      completed the questionnaire in the presence of the physician. For the first 201
      questionnaires collected, the corresponding children and adolescents underwent a
      spine medical examination, with evaluation of pain by visual analog scale if LBP
      was present. A stepwise logistic regression analysis was carried out to determine
      the risk factors associated with LBP and chronic LBP. The cumulative lifetime
      prevalence of LBP was 28.4%. Eight percent of the subjects suffered from chronic
      LBP. LBP was responsible for 23% of school absenteeism and 29% for sports
      absenteeism. Medical care requirement was observed in 32.2% and psychological
      symptoms in 75%. Stepwise logistic regression analysis showed that three factors
      were associated with LBP: school failure (held back 1 year), odds ratio (OR) =2.6
      (95% confidence interval [CI], 1.96-3.44), family history of LBP (parental or
      sibling LBP), OR=3.80 (95% CI, 2.94-5.92), dissatisfaction with school chair (in
      height and comfort), OR=3.40 (95% CI, 2.24-5.29). Two factors were associated
      with chronic LBP: dissatisfaction with school chair, OR=1.62 (95% CI, 1.46-3.32)
      and football playing, OR=3.07 (95% CI, 2.15-5.10). The prevalence of LBP among
      Tunisian schoolchildren and adolescents is high. This requires preventive
      measures and longitudinal studies, which are very important from the standpoint
      of public health.

PMID- 15940480
TI  - Cervical intervertebral disc injury during simulated frontal impact.
AB  - Cervical disc injury due to frontal impact has been observed in both clinical and
      biomechanical investigations; however, there is a lack of data that elucidate the
      mechanisms of disc injury during these collisions. The goals of the current study
      were to determine the peak dynamic disc annular tissue strain and disc shear
      strain during simulated frontal impact of the whole human cervical spine model
      with muscle force replication at 4 g, 6 g, 8 g and 10 g horizontal accelerations
      of the T1 vertebra. These data were compared with those obtained during
      physiological loading, and with previously reported rear impact data. Peak disc
      shear strain and peak annular tissue strain during frontal impact exceeded
      (p<0.05) corresponding physiological limits at the C2-C3 intervertebral level,
      beginning at 4 g and 6 g, respectively. These subsequently spread throughout the
      entire cervical spine at 10 g, with the exception of C4-C5. The C5-C6
      intervertebral level was at high risk for injury during both frontal and rear
      impacts, while during frontal impact, in addition to C5-C6, subfailure injuries
      were likely at superior intervertebral levels, including C2-C3. The disc injuries
      occurred at lower impact accelerations during rear impact as compared with
      frontal impact. The subfailure injuries of the cervical intervertebral disc that
      occur during frontal impact may lead to the chronic symptoms reported by
      patients, such as head and neck pain.

PMID- 15940481
TI  - Differential activity of regions of transversus abdominis during trunk rotation.
AB  - The role of the abdominal muscles in trunk rotation is not comprehensively
      understood. This study investigated the electromyographic (EMG) activity of
      anatomically distinct regions of the abdominal muscles during trunk rotation in
      six subjects with no history of spinal pain. Fine-wire electrodes were inserted
      into the right abdominal wall; upper region of transversus abdominis (TrA),
      middle region of TrA, obliquus internus abdominis (OI) and obliquus externus
      abdominis (OE), and lower region of TrA and OI. Surface electrodes were placed
      over right rectus abdominis (RA). Subjects performed trunk rotation to the left
      and right in sitting by rotating their pelvis relative to a fixed thorax. EMG
      activity was recorded in relaxed supine and sitting, and during an isometric hold
      at end range. TrA was consistently active during trunk rotation, with the
      recruitment patterns of the upper fascicles opposite to that of the middle and
      lower fascicles. During left rotation, there was greater activity of the lower
      and middle regions of contralateral TrA and the lower region of contralateral OI.
      The upper region of ipsilateral TrA and OE were predominately active during right
      rotation. In contrast, there was no difference in activity of RA and middle OI
      between directions (although middle OI was different between directions for all
      but one subject). This study indicates that TrA is active during trunk rotation,
      but this activity varies between muscle regions. These normative data will assist
      in understanding the role of TrA in lumbopelvic control and movement, and the
      effect of spinal pain on abdominal muscle recruitment.

PMID- 15940483
TI  - Monocular diplopia after neodymium: YAG laser capsulotomy.
AB  - PURPOSE: To present an unusual complication of posterior capsulotomy such as
      monocular diplopia and to discuss the importance of capsulotomy size. METHODS: 
      CASE REPORT: A 57-year old man came to our clinic complaining of horizontal
      monocular diplopia in his right eye for the past 3 days. The patient had
      undergone a Nd:YAG capsulotomy in this eye 3 weeks before. Slit-lamp
      biomicroscopy under pupil dilation revealed a small capsulotomy and a
      considerable Elschnig pearl as the presumable cause of the diplopia. The rest of
      the examination was completely normal. RESULTS: After repeat Nd:YAG capsulotomy
      treatment, the diplopia disappeared. CONCLUSION: Capsulotomy size is a
      significant factor to consider when treating a posterior capsular opacification.
      A capsulotomy that is larger than the pupil diameter under scotopic conditions
      may avoid disturbances of vision such as monocular diplopia.

PMID- 15940484
TI  - Bullous keratopathy as a complication of trabeculectomy with mitomycin C.
AB  - BACKGROUND: The routine use of mitomycin C to enhance glaucomatous filtering
      surgery has found wide acceptance. Complications of the application of mitomycin
      C have been repeatedly noticed. We now report a previously undescribed
      complication showing a toxic effect of mitomycin C to the corneal endothelium.
      METHODS: Patients underwent routine trabeculectomy with mitomycin C. Following
      surgery, the eyes were examined by biomicroscopy and specular microscopy of the
      corneal endothelium. RESULTS: In two cases, we observed a partial decompensation
      of the corneal endothelium resulting in a well-demarcated clear zone of the
      cornea and a second zone with thickening of the cornea and a bullous keratopathy
      adjacent to the filtering bleb. The specular microscopy showed marked
      irregularities of the endothelial cells and areas of necrosis in those parts of
      the cornea close to the filtering bleb. CONCLUSIONS: The two cases described here
      demonstrate that if the corneal endothelium is already compromised before
      surgery, the application of mitomycin C may have an additional toxic effect on
      the endothelium and may result in a partial bullous keratopathy. Surgeons should
      be aware of this complication.

PMID- 15940485
TI  - Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary
      acquired melanosis with atypia: 12 years' experience.
AB  - PURPOSE: To report 12-year follow-up experience with topical mitomycin
      chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with
      atypia and conjunctival melanoma. METHODS: Interventional case series of 16
      patients. Mitomycin was a primary treatment for residual epithelial disease in
      ten patients (eight with PAM with atypia and two with conjunctival melanoma) and
      as an adjuvant to excision and cryotherapy in six with conjunctival malignant
      melanoma. Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14
      day cycles) and for 7 consecutive days as adjuvant therapy. Patients were
      followed for both local recurrence and metastatic disease. RESULTS: Sixteen
      patients were followed for a mean 81 months (range 13-144 months) after
      treatment. All tumors responded to chemotherapy. Recurrence was noted in eight
      (three adjuvant and five primary treatment patients). Three underwent orbital
      exenteration. The remaining five were treated conservatively. The mean time to
      recurrence was 36.9 months. The short-term mitomycin-related complications
      included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1)
      and one corneal abrasion with scar formation. The long-term complications
      included pannus (n=2) and corneal haze (n=1). Visual acuity was maintained within
      two lines in 14 patients (including measurements just prior to exenteration).
      Three patients died, one of metastatic conjunctival melanoma. CONCLUSIONS:
      Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy;
      subepithelial nests appeared resistant to treatment. Treatment-related
      complications were acceptable. In this series, as primary and adjuvant therapy,
      topical mitomycin yielded an overall recurrence rate of 50%.

PMID- 15940486
TI  - Usefulness of MRI for diagnosis of painful snapping elbow.
AB  - Painful snapping of the elbows is rare. We report on a 12-year-old boy with a
      painful snap in both elbows. High-resolution magnetic resonance imaging of the
      elbow using microscopy coils detected a synovial fold interposed in each
      humeroradial joint and was very helpful in establishing the cause of symptoms.
      Resection of the synovial folds was performed with subsequent relief of symptoms.

PMID- 15940487
TI  - Is intra-articular pathology associated with MCL edema on MR imaging of the non
      traumatic knee?
AB  - OBJECTIVE: Edema surrounding the medial collateral ligament (MCL) is seen on MR
      imaging in patients with MCL injuries and in patients with radiographic
      osteoarthritis in the non-traumatic knee. Because we noted MCL edema in patients
      without prior trauma or osteoarthritis, we studied the association between intra
      articular pathology and MCL edema in patients without knee trauma. DESIGN AND
      PATIENTS: We evaluated the MR examinations of 247 consecutive patients (121 male,
      126 female with a mean age of 44 years) without recent trauma for the presence of
      edema surrounding the MCL, meniscal and ACL tears, medial meniscal extrusion,
      medial compartment chondromalacia, and osteoarthritis. The percentages of
      patients illustrating MCL edema with and without each type of pathology were
      compared using Fisher's exact test to determine if there was a statistically
      significant association. RESULTS: We found MCL edema in 60% of 247 patients. MCL
      edema was present in 67% of patients with medial meniscal tears, 35% with lateral
      meniscal tears, 100% with meniscal extrusion of 3 mm or more, 78% with femoral
      chondromalacia, 82% with tibial chondromalacia, and 50% with osteoarthritis. The
      percentage of patients with edema increased with the severity of the
      chondromalacia. These associations were all statistically significant (p <0.02).
      The mean age of those with MCL edema was 49.7 years compared with 34.9 years
      without MCL edema ( p <0.001). Patient gender and ACL tear did not correlate with
      MCL edema. Nine (4%) of the 247 patients had MCL edema without intra-articular
      pathology. None of these 9 patients had MCL tenderness or joint laxity on
      physical examination. CONCLUSIONS: We confirmed that MCL edema is associated with
      osteoarthritis, but is also associated with meniscal tears, meniscal extrusion,
      and chondromalacia. In addition, MCL edema can be seen in patients without intra
      articular pathology, recent trauma or MCL abnormality on physical examination.

PMID- 15940488
TI  - Spontaneous collapse of the tibial plateau: radiological staging.
AB  - OBJECTIVE: This paper proposes a radiological staging system for necrosis of the
      tibial plateau, similar to those already developed for the hip and the medial
      femoral condyle. DESIGN AND PATIENTS: We retrospectively studied the clinical
      case histories and radiographic findings of 14 patients (15 affected knees) with
      histologically proven osteonecrosis of the tibial plateau. RESULTS: Stage I was
      marked by normal radiograph, but increased uptake in bone scan and subchondral
      areas of abnormal marrow signal intensity in magnetic resonance imaging (MRI), as
      reported in other osteonecrosis sites. Stage II was characterised by cystic and
      sclerotic changes, and stage III fracture of the medial rim of the medial tibial
      plateau and tibial plateau collapse were present. Stage IV was marked by joint
      narrowing. These changes appeared earlier and were more pronounced when there was
      genu varum/valgum or involvement of the lateral tibial plateau. CONCLUSIONS: The
      radiological evolution of the disease appears to follow a four-stage course over
      a period of roughly one year from the onset of symptoms.

PMID- 15940489
TI  - Pes anserine bursitis: incidence in symptomatic knees and clinical presentation.
AB  - OBJECTIVE: To determine the prevalence and associated clinical symptoms of pes
      anserine bursitis in symptomatic adult knees. MATERIALS AND METHODS: A
      retrospective review was performed of the reports of 509 knee MRI studies
      obtained from July 1998 to June 2004 on 488 patients presenting to an orthopaedic
      clinic with knee pain suspected to be due to internal derangement. The MRI
      studies and case histories of all patients reported to have pes anserine bursitis
      were reviewed. The management of these patients was also noted. RESULTS AND
      CONCLUSIONS: The prevalence of pes anserine bursitis as detected on MRI is 2.5%.
      The commonest clinical presentation was pain along the medial joint line
      mimicking a medial meniscal tear. We suggest that an accurate diagnosis of pes
      anserine bursitis on MRI will help prevent unnecessary arthroscopy and possibly
      initiate early treatment of the condition. Axial imaging is important in these
      cases to differentiate the bursa from other medial fluid collections.

PMID- 15940490
TI  - Isolated lower extremity metastases, 9 years after initial diagnosis of
      retinoblastoma.
AB  - We report the development of isolated lower extremity metastases, in a child, 9
      years after her initial diagnosis and treatment of bilateral infantile
      retinoblastomas. The radiographic, scintigraphic, computed tomographic, and
      magnetic resonance imaging findings are discussed. The dominant metastatic focus
      was blastic, involving the medial cuneiform. Additional occult lesions were found
      in the base of the second metatarsal, middle cuneiform, navicular and tibial
      diaphysis. An open biopsy confirmed the diagnosis. The occurrence of late distant
      metastases is rare in the USA.

PMID- 15940491
TI  - [Management of pulmonary embolism].
AB  - Venous thromboembolism is often triggered by transient episodes of increased risk
      but may occur spontaneously in patients with permanently increased risk.
      Pulmonary embolism may cause impairment of respiratory and circulatory function
      which can vary in severity from silent to catastrophic. The diagnosis can be
      feasibly established by detecting vein thrombosis. If this approach fails,
      demonstration of pulmonary emboli by lung scans becomes necessary to establish
      the diagnosis. A D-dimer-test can select patients in whom imaging of pulmonary
      perfusion is required. Immediate therapeutic anticoagulation with heparins is
      mandatory in confirmed thromboembolism, and is followed by a vitamin K
      antagonist. In the initial work-up, patients also have to be evaluated for
      systemic thrombolytic therapy by hemodynamic parameters and echocardiography. In
      a triggered episode of venous thromboembolism, duration of anticoagulation is
      confined to several months while spontaneous or recurrent events require
      prolonged or indefinite treatment.

PMID- 15940492
TI  - Cerebral oxygen saturation and electrical brain activity before, during, and up
      to 36 hours after arterial switch procedure in neonates without pre-existing
      brain damage: its relationship to neurodevelopmental outcome.
AB  - OBJECTIVE: To monitor the pattern of cerebral oxygen saturation (rSat), by use of
      NIRS, in term infants before, during and after the arterial switch operation and
      to evaluate its relation to neurodevelopmental outcome. METHODS: In 20 neonates
      without pre-existing brain damage hemodynamics and arterial oxygen saturation
      (AO2-Sat) were monitored simultaneously with rSat and amplitude-integrated EEG
      (aEEG) from 4 h to 12 h before up to 36 h after cardiopulmonary bypass (CPB) and
      short duration of cardiac arrest during deep hypothermia (DHCA). The Bayleys
      developmental scale was performed at 30 months. RESULTS: Before surgery rSat was
      <50% in 16 patients. During CPB rSat increased to normal values, with a sharp
      decrease during brief CA (median 6.5 min). Post-CPB rSat showed a transient
      decrease (30-45%) despite normal PaO2 with sustained normalization after 6-26 h.
      Recovery time of the rSat seemed longer when pre-operative rSat was below 35%,
      and for lower minimum nasopharyngeal temperature and longer duration of CPB and
      of DHCA. Recovery time of the aEEG varied and did not correlate with
      normalization of rSat. Neurodevelopmental outcome was normal in all but two
      patients. Patients with lower pre-operative rSat (<35%) tended to have lower DQ
      (developmental quotient) scores at 30-36 months. (median: mental 102 and motor
      101 (range 58-125) compared with mental 100 and motor 110 (range 83-125))
      CONCLUSION: Despite prompt normalization of circulation and oxygenation after
      surgery, recovery of rSat of the brain took 6-26 h, probably because of higher
      energy demand after CPB. Pre-operative cerebral oxygenation may be underestimated
      as a possible cause of adverse post-operative outcome.

PMID- 15940493
TI  - Mental maze solving: directional fMRI tuning and population coding in the
      superior parietal lobule.
AB  - The superior parietal lobule (SPL) of six human subjects was imaged at 4 T during
      mental traversing of a directed maze path. Here we demonstrate the orderly
      involvement of the SPL in this function, as follows. Forty-two percent of the
      voxels were tuned with respect to the direction of the maze path. This suggests a
      coherent tuning of local neuronal populations contributing to the change of the
      single-voxel BOLD signal. Preferred directions ranged throughout the directional
      continuum of 360 degrees. Voxels with similar preferred directions tended to
      cluster together: on average there were seven same-direction clusters per slice,
      with an average cluster membership of five voxels/cluster and an average nearest
      neighbor same-direction intercluster distance of 13.1 mm. On the other hand, the
      average nearest-neighbor intercluster distance between a given direction and all
      other directions was 3.1 mm. This suggests a patchy arrangement such that patches
      of directionally tuned voxels, containing voxels with different preferred
      directions, alternate with patches of non-tuned voxels. Finally, the population
      vector predicted accurately the direction of the maze path (with an error of 12.7
      degrees), and provided good estimates (with an error of 29 degrees) when
      calculated within parts of the SPL. Altogether, these findings document a new,
      orderly functional organization of the SPL with respect to mental tracing.

PMID- 15940494
TI  - Postural responses triggered by multidirectional leg lifts and surface tilts.
AB  - The aim of the present study was to investigate the relationship between
      proactive and reactive components of postural control. We contrasted the
      kinematic and electromyographic (EMG) responses to multidirectional voluntary leg
      lifts with those elicited by unexpected surface tilts. In particular, we
      addressed the role of trunk stabilization following either a voluntary or forced
      weight shift from double to single limb support. Nine young female subjects stood
      with a standing posture of 45 degrees toe-out and their arms abducted to shoulder
      level. On the experimenter's signal, subjects either (1) lifted one leg as fast
      as possible in one of six directions (R/L side, R/L diagonal front, R/L diagonal
      back) to a height of 45 degrees or (2) maintained standing as the support surface
      tilted at a rate of 53 degrees /s to a height of 10 degrees in one of six
      directions (R/L-up, R/L diagonal toes-up, R/L diagonal toes-down). For both
      tasks, our results showed that the center of pressure (COP) displacement began
      before or in conjunction with displacement of the center of mass (COM), after
      which the COP oscillated about the horizontal projection of the COM. In addition,
      the muscles were recruited in a distal-to-proximal sequence, either in
      anticipation of the voluntary leg lift or in response to the sudden surface tilt.
      Thus, the COP was being used dynamically to control displacement of the COM. The
      axial postural strategy comprising head, trunk, and pelvis movements was
      quantified by means of principal component analysis. More than 95% of the
      variance in the data could be described by the first two eigenvectors, which
      revealed specific coordination patterns dominated by pelvis rotation in one
      direction and head/trunk rotation in the opposite direction. Unexpected surface
      tilting elicited an automatic response strategy that focused on controlling the
      orientation of the head and trunk with respect to the vertical gravity vector
      while trunk verticality was compromised for movement generation and the recovery
      of postural equilibrium during leg lifting. In conclusion, regardless of the type
      (voluntary versus involuntary) or direction of perturbation, the strategy
      employed by the central nervous system to control the body COM displacement
      concerns mainly trunk stabilization.

PMID- 15940496
TI  - The effect of time to peak ankle torque on balance stability boundary:
      experimental validation of a biomechanical model.
AB  - Pai and Patton (1997), using a biomechanical model, determined a set of feasible
      center of mass (CM) velocity-position combinations (balance stability boundary)
      that guarantee upright stability. In their study, the magnitude of the restoring
      ankle torque was used to study the subject's ability to recover balance. Recent
      studies have suggested that the ability to maintain a stable posture depends not
      only on the magnitude of the restoring torque but also on the time to generate
      this torque. The objectives of the present study were: (1) to build a
      biomechanical model that predicts the balance stability boundary which includes
      time to peak ankle torque, (2) to determine the capability of the model to
      predict successful and failed experimental balance recovery trials, and (3) to
      compare the predictive capability of the biomechanical model with that of a
      statistical model (logistic regression). A single-link-plus-foot biomechanical
      model was used to determine a set of balance stability boundaries, computed from
      the combination of maximum CM velocity and related CM position, for various times
      to peak ankle torque. An experiment was conducted to validate the biomechanical
      model. The participants self-initiated a forward destabilization and were asked
      to regain balance using an ankle feet-in-place strategy. Also, a forward stepwise
      logistic regression (predictors: CM position and velocity and time to peak ankle
      torque) was used to discriminate between successful and failed experimental
      trials. (1) The outcomes of the biomechanical model confirmed that the time to
      peak ankle torque drastically constrained the stability boundaries. (2) The
      biomechanical model predicted 79.9% of the failed experimental trials and 74.5%
      of the successful experimental trials. (3) The stepwise logistic regression
      included all independent variables and predicted 57.2% of the failed and 93.7% of
      the successful experimental trials. Hence, the biomechanical model showed better
      predictive capability than the statistical model for identifying unsuccessful
      balance recovery. It is noteworthy that the balance stability boundaries
      constrained by the speed of ankle torque development predicted the outcome of the
      experimental trial earlier in the time series than balance stability boundary
      constrained by constant ankle torque. Overall, the present biomechanical model
      may serve as an assessment tool to develop specific interventions towards
      improving a patient's speed of ankle torque development and to possibly reduce
      falling frequency.

PMID- 15940495
TI  - Cortical afferents to the smooth-pursuit region of the macaque monkey's frontal
      eye field.
AB  - In primates, the frontal eye field (FEF) contains separate representations of
      saccadic and smooth-pursuit eye movements. The smooth-pursuit region (FEFsem) in
      macaque monkeys lies principally in the fundus and deep posterior wall of the
      arcuate sulcus, between the FEF saccade region (FEFsac) in the anterior wall and
      somatomotor areas on the posterior wall and convexity. In this study, cortical
      afferents to FEFsem were mapped by injecting retrograde tracers (WGA-HRP and fast
      blue) into electrophysiologically identified FEFsem sites in two monkeys. In the
      frontal lobe, labeled neurons were found mostly on the ipsilateral side in the
      (1) supplementary eye field region and lateral area F7; (2) area F2 along the
      superior limb of the arcuate sulcus; and (3) in the buried cortex of the arcuate
      sulcus extending along the superior and inferior limbs and including FEFsac and
      adjacent areas 8, 45, and PMv. Labeled cells were also found in the caudal
      periprincipal cortex (area 46) in one monkey. Labeled cells were found
      bilaterally in the frontal lobe in the deep posterior walls of the arcuate sulcus
      and postarcuate spurs and in cingulate motor areas 24 and 24c. In postcentral
      cortical areas all labeling was ipsilateral and there were two major foci of
      labeled cells: (1) the depths of the intraparietal sulcus including areas VIP,
      LIP, and PEa, and (2) the anterior wall and fundus of the superior temporal
      sulcus including areas PP and MST. Smaller numbers of labeled cells were found in
      superior temporal sulcal areas FST, MT, and STP, posterior cingulate area 23b,
      area 3a within the central sulcus, areas SII, RI, Tpt in the lateral sulcus, and
      parietal areas 7a, 7b, PEc, MIP, DP, and V3A. Many of these posterior afferent
      cortical areas code visual-motion (MT, MST, and FST) or visual-motion and
      vestibular (PP, VIP) signals, consistent with the responses of neurons in FEFsem
      and with the overall physiology and anatomy of the smooth-pursuit eye movement
      system.

PMID- 15940498
TI  - Peripheral vision for perception and action.
AB  - Anatomical and physiological evidence suggests that vision-for-perception and
      vision-for-action may be differently sensitive to increasingly peripheral
      stimuli, and to stimuli in the upper and lower visual fields (VF). We asked
      participants to fixate one of 24 randomly presented LED arranged radially in
      eight directions and at three eccentricities around a central target location.
      One of two (small, large) target objects was presented briefly, and participants
      responded in two ways. For the action task, they reached for and grasped the
      target. For the perception task, they estimated target height by adjusting thumb
      finger separation. In a final set of trials for each task, participants knew that
      target size would remain constant. We found that peak aperture increased with
      eccentricity for grasping, but not for perceptual estimations of size. In
      addition, peak grip aperture, but not size-estimation aperture, was more variable
      when targets were viewed in the upper as opposed to the lower VF. A second
      experiment demonstrated that prior knowledge about object size significantly
      reduced the variability of perceptual estimates, but had no effect on the
      variability of grip aperture. Overall, these results support the claim that
      peripheral VF stimuli are processed differently for perception and action.
      Moreover, they support the idea that the lower VF is specialized for the control
      of manual prehension. Finally, the effect of prior knowledge about target size on
      performance substantiates claims that perception is more tightly linked to memory
      systems than action.

PMID- 15940497
TI  - Patterns of spontaneous activity in unstructured and minimally structured spinal
      networks in culture.
AB  - The rhythmic activity observed in locomotion is generated by local neuronal
      networks in the spinal cord. The alternating patterns are produced by reciprocal
      connections between these networks. Synchronous rhythmic activity, but not
      alternation, can be reproduced in disinhibited networks of dissociated spinal
      neurons of rats. This suggests that a specific network architecture is required
      for pattern generation but not for rhythm generation. Here we were interested in
      the recruitment of neurons to produce population bursts in unstructured and
      minimally structured cultures of rat spinal cord grown on multielectrode arrays.
      We tested whether two networks, connected by a small number of axons, could be
      functionally separated into two units and generate more complex patterns such as
      alternation. In the unstructured cultures, we found that the recruitment of the
      neurons into bursting populations is divided into two steps: the fast recruitment
      of a "trigger network", consisting of intrinsically firing cells connected in
      networks with short delays, and slow recruitment of the rest of the network. One
      or several trigger networks were observed in a single culture and could account
      for variable patterns of propagation. In the minimally structured cultures, a
      functional separation between loosely connected networks was achieved. Such
      separation led either to an independent bursting between the networks or to
      synchronized bursting with long and variable delays. However, no qualitatively
      novel pattern such as alternation could be generated. In addition, we found that
      the strength of reciprocal inhibitory connections was modulated by spontaneous
      activity.

PMID- 15940499
TI  - Proactive stability control while carrying loads and negotiating an elevated
      surface.
AB  - In this study, proactive stability control while handling loads and negotiating
      an elevated surface was examined. Ten young healthy males completed two gait-mode
      conditions--level walking and negotiating a raised surface. Load-handling
      conditions were: no load, empty box (reduced visual information), and loaded box
      (reduced visual information combined with increased inertial load). The lower
      limb trajectory in the sagittal plane was not modified as a function of reduced
      visual information or increased inertial load. The step width decreased while
      stepping over the surface and carrying the loaded box. The trunk pitch angle was
      biased backwards for both the empty box and the loaded box. When carrying the
      empty box and negotiating the surface, the trunk pitch range of motion (ROM)
      increased which may have been a strategy to increase visual exteroceptive
      information. As increased net trunk pitch could destabilize the system,
      concurrent stabilizing strategies--decreased gait velocity and reduced net trunk
      roll velocity--were observed. To meet the equilibrium goals when carrying the
      loaded box, the trunk pitch ROM and net pitch velocity were reduced during both
      level walking and surface accommodation. Trunk roll ROM was reduced when carrying
      the load and negotiating the surface. This study extends our knowledge regarding
      whole body coordination strategies during anticipatory locomotor adaptations.

PMID- 15940500
TI  - Kinematic properties of on-line error corrections in the monkey.
AB  - Despite the abundant experimental evidence for the irregular, multipeaked
      velocity profiles that often characterize rapid human limb movements, there is
      currently little agreement on how to interpret these phenomena. While in some
      studies these irregularities have been interpreted as reflecting a continuous
      control process, in others the irregularities are considered to be evidence for
      the existence of discrete movement primitives that are initiated by an
      intermittent controller. Here we introduce a novel "soft symmetry" method for
      analyzing irregular movements and decomposing them into their discrete movement
      primitives. We applied this method to analyze rapid pronation/supination wrist
      movements in monkeys during a one-dimensional tracking task. We showed that the
      properties of the extracted overlapping submovements (OSMs) were very similar to
      those of single, regular movements, despite the fact that the decomposition
      algorithm did not restrict the extracted submovements to a particular shape. In
      addition we showed that the movement primitives corrected preceding primitives
      and that the correction initiation time was highly variable, and thus could not
      be explained by the relatively fixed sensorimotor delay. These results argue
      against the interpretation of movement irregularities as reflecting a continuous
      control process and reinforce the hypothesis that movement irregularities result
      from an intermittent control mechanism. Demonstrating these phenomena in non
      human primates will allow neurophysiological investigation of the neural
      mechanisms involved in these corrections.

PMID- 15940502
TI  - Synaptic potentiation induced by rTMS: effect of lidocaine infusion.
AB  - Repetitive transcranial magnetic stimulation (rTMS) delivered at various
      intensities and frequencies excites cortical motor areas. Trains of stimuli (at 5
      Hz frequency, and suprathreshold intensity) progressively increase the size of
      motor evoked potentials (MEPs) and the duration of the cortical silent period
      (CSP) in normal subjects. Because antiepileptic drugs, acting mainly on sodium
      channels, depress MEP facilitation during rTMS, we suggested that rTMS trains
      facilitate the MEP size by inducing synaptic potentiation primarily involving
      voltage-gated sodium channels. The aim of this study was to evaluate the effect
      of lidocaine-a drug that acts selectively on sodium channels-on the rTMS-induced
      changes in cortical excitability. We tested the changes in motor threshold, MEP
      size, CSP duration evoked by focal rTMS and the M-wave amplitude in healthy
      subjects before and after lidocaine infusion. Lidocaine abolished the normal rTMS
      induced facilitation of MEPs but left the other rTMS variables and the M-wave
      unchanged. Our results suggest that the MEP facilitation related to rTMS-induced
      synaptic potentiation results from an increase in cortical excitatory interneuron
      excitability that involves voltage-gated sodium channels.

PMID- 15940501
TI  - Otolith organ or semicircular canal stimulation induces c-fos expression in
      unipolar brush cells and granule cells of cat and squirrel monkey.
AB  - Immediate early gene expression in the cerebellar vermis of cats and squirrel
      monkeys was stimulated by prolonged whole body rotations. Continuous, earth
      horizontal axis rotations that excited only otoliths or high velocity vertical
      axis rotations that excited only semicircular canals resulted in c-fos
      immunoreactive nuclei concentrated in the granular layer of lobules X and ventral
      IX (the nodulus and ventral uvula), which represent the medial parts of the
      vestibulo-cerebellum. Large clusters of labeled nuclei consisting mainly of
      granule cells and calretinin-positive unipolar brush cells were present in the
      granular layer, whereas Purkinje cell nuclei were unlabeled, and labeled basket
      and stellate cell nuclei were scattered in the molecular layer. In other vermal
      lobules there was a significant but less dense label than in the nodulus and
      ventral uvula. Generally, the extent of c-fos labeling of molecular layer
      interneurons was in relation to nuclear labeling of granular layer neurons:
      labeling of both basket and stellate cells accompanied nuclear labeling of
      neurons throughout the depth of the granular layer, whereas only stellate cells
      were labeled when nuclear labeling was restricted to the superficial granular
      layer. Yaw horizontal or roll vertical rotations each stimulated c-fos expression
      in the cat medial vestibulo-cerebellum to approximately the same extent. Low
      velocity rotations resulted in much less c-fos expression. Similar, albeit less
      intense, patterns of c-fos activation were observed in monkeys. Concentrated c
      fos expression in the medial vestibulo-cerebellum after exposure to a strong head
      velocity signal that could originate from either otolith or canal excitation
      suggests that granule and unipolar brush cells participate in a neuronal network
      for estimating head velocity, irrespective of the signal source.

PMID- 15940503
TI  - Intermanual and intramanual tactual grating discrimination.
AB  - For intermanual tactual discrimination to occur, it is thought that neural
      signals have to cross the corpus callosum in some way at least once. In this note
      we address the question of whether this interhemispheric transfer affects grating
      discrimination in active touch. Eight right-handed participants made intermanual
      and intramanual tactual discriminations of sinusoidal gratings that had slightly
      different spatial periods. Intramanual discrimination included comparisons in
      which the gratings were felt with the same finger, as well as comparisons made
      with two different fingers of the same hand. During intermanual discrimination
      the gratings were felt with corresponding fingers or with non-corresponding
      fingers of different hands. We found that thresholds for intramanual conditions
      were lower than for intermanual conditions in active dynamic touch. This suggests
      that there is a component of the task that is unilateral, as might be mediated by
      a somatosensory region that has predominantly or exclusively contralateral
      receptive fields.

PMID- 15940504
TI  - [Clinical pathways in psychiatry and psychotherapy].
AB  - BACKGROUND: Implementing evidence-based clinical guidelines by means of clinical
      pathways is one of the key elements of continuous quality management at the
      University Hospital of Marburg. This paper explains how clinical pathways for
      suicidal ideation and suicide attempts were developed. METHODS: Based upon a
      review of existing guidelines and literature, optimal standards of care were
      defined. Step-by-step analysis of the process of care and results of a
      questionnaire were used to describe the actual processes. A problem-orientated
      comparison of the actual and the optimal process of care was the basis for
      developing these pathways. A consensus was achieved with all persons involved in
      the respective process of care taking into consideration local resources as well
      as barriers. The most important decisions and interventions were defined and
      presented as a patient-oriented process. RESULTS: The lack of explicit "how to do
      it"-recommendations of the guidelines for the entire care processes required
      specific, locally tailored adaptations. Potentials for improvement were
      identified in the following areas: transfer of patients, consultation,
      information and coordination within the team, and diagnosis of suicide risk. The
      pathways include care-oriented algorithms, checklists and assignments of
      responsibility. CONCLUSIONS: The development of clinical pathways as part of
      quality management and transsectoral integrated care in psychiatry and
      psychotherapy is feasible. The concept presented incorporates the potential of
      increasing transparency, efficiency and efficacy of care, and of improving
      satisfaction of those involved. It offers psychiatric hospitals the chance to
      guarantee optimal quality of care in face of increasing workload and costs.

PMID- 15940505
TI  - Rapidly destructive coxopathy after subchondral insufficiency fracture of the
      femoral head.
AB  - Rapidly destructive coxopathy (RDC) is a rare disorder, and its pathophysiology
      is unknown. Here, we report a case of RDC evaluated by roentgenography and
      magnetic resonance imaging, from the onset of hip pain without changes on
      roentgenograms, to the terminal stage with collapse of the femoral head. Our
      serial radiological findings clearly illustrate the entire process of RDC,
      especially the initial stage. Subchondral insufficiency fracture of the femoral
      head seems to be an important preliminary event in the development of RDC.

PMID- 15940507
TI  - Simultaneous measurements of local tissue temperature and blood perfusion rate in
      the canine prostate during radio frequency thermal therapy.
AB  - Local tissue temperature and blood perfusion rate were measured simultaneously to
      study thermoregulation in the canine prostate during transurethral radio
      frequency (RF) thermal therapy. Thermistor bead microprobes measured interstitial
      temperatures and a thermal clearance method measured the prostatic blood
      perfusion rate under both normal and hyperthermic conditions. Increase in local
      tissue temperature induced by the RF heating increased blood perfusion throughout
      the entirety of most prostates. The onset of the initial increase in blood
      perfusion was sometimes triggered by a temporal temperature gradient at low
      tissue temperatures. When tissue temperature was higher than 41 degrees C,
      however, the magnitude and the spatial gradient of temperature may play
      significant roles. It was found that the temperature elevation in response to the
      RF heating was closely coupled with local blood flow. The resulting decrease in
      or stabilization of tissue temperature suggested that blood flow might act as a
      negative feedback of tissue temperature in a closed control system. Results from
      this experiment provide insights into the regulation of local perfusion under
      hyperthermia. The information is important for accurate predictions of
      temperature during transurethral RF thermal therapy.

PMID- 15940506
TI  - Effects of fixation and decalcification on the immunohistochemical localization
      of bone matrix proteins in fresh-frozen bone sections.
AB  - To examine the stability of bone matrix proteins for crystal dislocation, the
      immunolocalization of type I collagen, bone sialoprotein, and osteopontin was
      investigated during different stages of fixation and decalcification. Four-week
      old rat femurs were rapidly frozen, and were sectioned without fixation or
      decalcification. Thereafter, following or bypassing fixation in 4%
      paraformaldehyde, these sections were decalcified in 5% EDTA for 0-5 min. Before
      decalcification, marked radiopacity of bone matrix was observed in contact
      microradiography (CMR) images, and electron probe microanalysis (EPMA)
      demonstrated intense localization for phosphorus and calcium. In fixed and
      unfixed sections without decalcification, immunolocalization of bone matrix
      proteins were almost restricted to osteoid. After 1 min of decalcification,
      reduced radiopacity was apparent in the CMR images, and less phosphorus and
      calcium was observed by EPMA, which completely disappeared by 5 min
      decalcification. After 3-5 min of decalcification, unfixed sections showed that
      these proteins were immunolocalized in bone matrix, but were not detectable in
      osteoid. However, fixed sections demonstrated that these were found in both bone
      matrix and osteoid. The present findings suggest that bone matrix proteins are
      embedded in calcified matrix which is separated from the aqueous environment and
      that they hardly move, probably due to firm bonding with each other. In contrast,
      matrix proteins in osteoid are subject to loss after decalcification because they
      may be bound to scattered apatite crystals, not to each other.

PMID- 15940508
TI  - Patterns of AFLP variation in a core subset of cultivated hexaploid oat
      germplasm.
AB  - Many core collections have been developed from large collections of crop
      germplasm, but most of these have not been characterized, particularly using
      molecular techniques, for germplasm management and utilization. We have attempted
      to characterize a structured sample representing a world collection of 11,622
      cultivated hexaploid oat accessions in the hope of understanding the genetic
      structure of the world collection. The amplified fragment length polymorphism
      (AFLP) technique was applied to screen 670 accessions representing 79 countries
      and one group of uncertain origin. For each accession, 170 AFLP polymorphic bands
      detected by five AFLP primer pairs were scored. Analyses of the AFLP data showed
      the effectiveness of the stratified sampling applied in capturing country-wise
      AFLP variation. The frequencies of polymorphic bands ranged from 0.11 to 0.99,
      with an average of 0.72. The majority (89.9%) of the AFLP variation resided
      within accessions of each country, and only 6.2% of the AFLP differences existed
      among accessions of major geographic regions. Accessions from the Mediterranean
      region were the most distinct, while those from Russia and the USA were the most
      diverse. The two distinct groups that were observed were separated largely on the
      basis of common oat and red oat. Red oat was genetically more diverse than its
      common and hull-less counterparts, and hull-less oat was more related to common
      oat than red oat. Landrace and non-landrace accessions displayed similar AFLP
      variation patterns. These patterns are significant for understanding the
      domestication of cultivated oat and are useful in classifying the intraspecific
      diversity of oat germplasm, developing specific core subsets of the oat
      collection, and exploring new sources of genes for oat improvement.

PMID- 15940509
TI  - Fine mapping of the rice low phytic acid (Lpa1) locus.
AB  - Phytic acid is the primary storage form of phosphorus (P) in cereal grains. In
      addition to being essential for normal seedling growth and development, phytic
      acid plays an important role in human and animal nutrition. The rice low phytic
      acid mutation lpa1 results in a 45% reduction in seed phytic acid with a molar
      equivalent increase in inorganic P. The Lpa1 locus was previously mapped to the
      long arm of chromosome 2. Using microsatellite markers and a recombinant inbred
      line population, we fine mapped this locus between the markers RM3542 and RM482,
      which encompass a region of 135 kb. Additional markers were developed from the
      DNA sequence of this region. Two of these markers further delimited the locus to
      a 47-kb region containing eight putative open reading frames. Cloning and
      molecular characterization of the Lpa1 gene will provide insight into phytic acid
      biosynthesis in plants. The markers reported here should also be useful in
      introgressing the low phytic acid phenotype into other rice cultivars.

PMID- 15940510
TI  - Mapping of QTLs conferring extremely early heading in rice (Oryza sativa L.).
AB  - Two genes related to extremely early heading were identified in populations
      derived from crosses between Hoshinoyume, a variety adapted to the northernmost
      limit of rice cultivation (Hokkaido), and Nipponbare, a variety adapted to the
      temperate region of Japan. The segregations for heading date clearly revealed
      that a two-gene model determined the extremely early heading in the F(2) and
      BC(1)F(1) populations under natural field conditions in Hokkaido. Using molecular
      markers corresponding to ten known quantitative trait loci (QTLs) for heading
      date, we carried out QTL analysis in the BC(1)F(1) population and detected two
      QTLs, qDTH-7-1 and qDTH-7-2, both on chromosome 7, and observed epistatic
      interaction between them. We conclude that the recessive alleles of these two
      genes contribute to extremely early heading for the adaptation to Hokkaido
      environment and to stable rice production in Hokkaido. The relationships between
      the two QTLs identified in this study and known QTLs are discussed.

PMID- 15940511
TI  - En bloc resection of right-sided colonic adenocarcinoma with adjacent organ
      invasion.
AB  - BACKGROUND: Right-sided colon cancers that invade the adjacent organs are often
      missed on preoperative imaging. These patients are often considered unresectable
      at laparotomy as the surgeon is not prepared for en bloc resections. A few
      centers have reported extended survival after en bloc resection in such tumors.
      We therefore decided to evaluate the outcome of our patients after en bloc right
      hemicolectomy. PATIENTS AND METHODS: The records of all patients who underwent en
      bloc resection of adjacent organs for right colon cancers were analyzed. RESULTS:
      Between 1992 and 2004, 11 patients had an en bloc right hemicolectomy for right
      sided colon cancer. There were ten males and one female with a mean age of 44
      years (35-80 years). All patients had anaemia at presentation and most had weight
      loss and a fixed palpable lump. Preoperative CT scan was able to detect adjacent
      organ infiltration in nine patients. Six patients had an en bloc
      pancreaticoduodenectomy, three patients had en bloc local excision of duodenal
      wall, one patient had en bloc resection of segments 5 and 6 of the liver and one
      patient had en bloc distal gastrectomy. There was one operative mortality after
      an en bloc pancreaticoduodenectomy. The median disease-free survival was 54
      months. CONCLUSION: Right-sided colon cancers that invade adjacent organs in the
      absence of distant spread may be a subset of tumors that behave in a locally
      aggressive manner without causing hematogenous spread. En bloc resection of these
      tumors is possible, in select centers, with low mortality and morbidity and
      extended survival.

PMID- 15940512
TI  - Echo-enhanced ultrasound--a new imaging modality for the differentiation of
      pancreatic lesions.
AB  - INTRODUCTION: Echo-enhanced ultrasound is a newly available mode of imaging for
      differential diagnosis of pancreatic tumours. Ductal carcinomas are often
      hypovascularised compared with the surrounding tissue. Neuroendocrine tumours, on
      the other hand, are hypervascularised lesions. Tumours associated with
      pancreatitis have a different vascularisation pattern depending on inflammation
      and necrosis. Cystadenomas frequently have many vessels along the fibrotic
      strands. RESULTS: Data from prospective studies have demonstrated, on the basis
      of these imaging criteria, that the sensitivity and specificity of echo-enhanced
      sonography for differentiation of pancreatic masses are >or=85 and >or=90%,
      respectively. CONCLUSIONS: Pancreatic tumours have a different vascularisation
      pattern in echo-enhanced ultrasound. These characteristics can be used with high
      diagnostic accuracy for differential diagnosis.

PMID- 15940513
TI  - Correlations among serum leptin levels, complete blood count parameters and
      peripheral CD34(+) cell count in prepubertal obese children.
AB  - Leptin is a hormone produced by adipocytes that helps reduce body weight by
      depressing appetite and increasing metabolic activity. Leptin also promotes early
      hematopoiesis. The main aim of this study was to compare complete blood count
      (CBC) parameters and peripheral blood CD34(+) cell counts in prepubertal obese
      and nonobese children. Relationships between leptin levels and CBC parameters and
      peripheral CD34(+) progenitor cell counts in the obese group were also
      investigated. Thirty one healthy, prepubertal, obese children and 30 nonobese,
      age-matched prepubertal controls were included in the study. A fasting blood
      sample was collected from each subject, and CBC findings, serum leptin level, and
      peripheral blood CD34(+) progenitor cell count were recorded. In the obese group,
      the mean results for body mass index (BMI), BMI standard deviation score (BMI
      SDS), and serum leptin level were significantly higher than the corresponding
      control findings. There were no significant differences between the groups with
      respect to CBC parameters and CD34(+) cell percentage. In both the obese and
      control groups, the girls' serum leptin levels were significantly higher than the
      boys'. In the obese group, serum leptin level was strongly correlated with BMI
      and with BMI SDS (Pearson correlation coefficients r=0.70, p<0.001, and r=0.59,
      p<0.001, respectively) in both girls and boys. None of the CBC parameters nor
      CD34(+) progenitor cell percentage was correlated with leptin, BMI, or BMI SDS.
      The results indicate that serum leptin levels in obese children are positively
      correlated with BMI. However, in contrast to adults, high leptin level in
      childhood obesity does not seem to be associated with altered CBC parameters or
      increased peripheral CD34(+) progenitor cell count.

PMID- 15940514
TI  - Epstein-Barr virus reactivation after allogeneic stem cell transplantation
      without lymph node enlargement.

PMID- 15940515
TI  - Capillary leak syndrome caused by cytostatics.

PMID- 15940516
TI  - How predictable is the abundance of double gametocyte infections?
AB  - It has been proposed that erythrocytes, infected by one male and one female
      gametocyte, enhance malaria transmission by lowering encounter time between male
      and female gametes once inside the mosquito vector. This may have important
      implications if they occur in human Plasmodium infections. Double gametocyte
      infections (DGIs) have been found in Plasmodium cultures, but it is thought that
      they are an artefact due to the artificially high crowding of cultures. Here, we
      studied gametocyte density and DGI occurrence in Haemoproteus columbae infecting
      feral pigeons (Columba livia), to determine if crowding is the key factor
      producing DGIs. We demonstrate that DGIs are not a spurious phenomenon or an
      artefact of crowding, but occur in any gametocyte density in a proportion a bit
      higher than that expected by a Poisson distribution.

PMID- 15940517
TI  - Molecular characterization of crane Coccidia, Eimeria gruis and E. reichenowi,
      found in feces of migratory cranes.
AB  - Eimeria gruis and E. reichenowi have lethal pathogenicity to a number of species
      of cranes. These parasites develop at multiple organs or tissues in infected
      cranes, thus lacking the specificity of infection sites shown by other Eimeria
      spp. in spite of morphologic similarity. To date, there have been many reports of
      crane Eimeria infections, however, genetic examinations of these parasites have
      never been published. In the present study, we isolated oocysts of E. gruis and
      E. reichenowi from crane feces at a wintering area in Japan. By phylogenic
      analysis, we first demonstrated that partial sequences of the isolates formed
      their own cluster, located separately from other Eimeria spp.

PMID- 15940518
TI  - Mechanisms associated with Acanthamoeba castellanii (T4) phagocytosis.
AB  - Using fluorescein isothiocyanate (FITC)-labelled Escherichia coli, phagocytosis
      in Acanthamoeba is studied. This assay is based on the quenching effect of trypan
      blue on FITC-labelled E. coli. Only intracellular E. coli retain their
      fluorescence, which are easily discriminated from non-fluorescent adherent
      bacteria. Acanthamoeba uptake of E. coli is significantly reduced in the presence
      of genistein, a protein tyrosine kinase inhibitor. In contrast, sodium
      orthovanadate (protein tyrosine phosphatase inhibitor) increases bacterial uptake
      by Acanthamoeba. Treatment of Acanthamoeba with cytochalasin D (actin
      polymerization inhibitor) abolished the ability of Acanthamoeba to phagocytose E.
      coli suggesting that tyrosine kinase-mediated signaling may play a role in
      Acanthamoeba phagocytosis. In addition, we showed that phosphatidylinositol 3
      kinase (PI3K) plays an important role in Acanthamoeba uptake of E. coli. Role of
      mannose-binding protein in Acanthamoeba phagocytosis is discussed further.

PMID- 15940519
TI  - Infestation of Werneckiella equi on Icelandic horses, characteristics of
      predilection sites and lice dermatitis.
AB  - Lice infestations on horses caused by the lice Werneckiella (Damalinia) equi and
      Haematopinus equi are observed worldwide. In this study, the distribution and
      clinical manifestations of lice on Icelandic horses were examined. Thirty-eight
      out of 93 animals (40.86%) were identified as infested with W. equi. Sixty-eight
      animals (73.12%) presented dermatological lesions associated with lice
      infestation, while only 32 of these animals presented lice. Six animals had no
      clinical signs although of being lice-positive, and 19 animals (20.43%) showed
      neither lice nor clinical manifestations. Lice burdens varied from animal to
      animal, and clinical manifestations occurred at all levels of infestation. Focal
      alopecia was the main clinical sign (83.78%) on lice-positive horses, while
      scaling and crusts occurred in 10.81% and 9.68% of the cases, respectively.
      Clinical signs present in the head and the neck/mane area were found to be an
      indication of lice infestation in horses.

PMID- 15940520
TI  - Dermatological and parasitological evaluation of infestations with chewing lice
      (Werneckiella equi) on horses and treatment using imidacloprid.
AB  - Lice infestations in horses caused by the chewing louse Werneckiella (Damalinia)
      equi are observed worldwide. In the present study, the efficacy of 10%
      imidacloprid was tested on horses naturally infested with lice. Two groups of
      animals received a double application of 4 ml and 8 ml Advantage 10% spot-on on
      day 0 and 28 either. Horses, presenting dermatological signs with negative lice
      counts, were also included in this investigation. 40.86% of the horses presented
      positive lice counts and 84.21% of these animals showed clinical dermatologic
      signs. 65.45% of the lice-negative horses also showed clinical manifestations.
      Two days after treatment, lice counts dropped in both the treatment groups and on
      day 56, all animals were free of alive lice, and dermatological lesions decreased
      significantly (P<0.001) in both the lice-positive and the negative animals. No
      correlation (P>0.050) between lice burden and clinical signs was detected.

PMID- 15940521
TI  - Vitellogenesis in two spathebothriidean cestodes.
AB  - Vitellogenesis in two spathebothriidean tapeworms, dixenous adult Cyathocephalus
      truncatus and monoxenous progenetic Diplocotyle olrikii, has been examined using
      transmission electron microscopy and cytochemical staining with periodic acid
      thiosemicarbazide-silver proteinate for glycogen. Each vitelline follicle
      consists of vitellocytes at various stages of development and one irregularly
      shaped interstitial cell. Projections of the interstitial cell enclose the
      vitellocytes and extend as a cytoplasmic sheath on the follicular periphery. An
      outer thin fibrous layer (= extracellular lamina) covers the cytoplasmic sheath
      in C. truncatus, but lacks in D. olrikii. Maturing and mature vitellocytes
      contain vitelline material in the form of single small shell globules that
      gradually fuse and give rise to the large shell globule clusters. Morphology of
      shell globule clusters differs slightly in both species. In addition, single
      "lamellar" granules are present in the cytoplasm of vitellocytes of C. truncatus,
      but not in D. olrikii. Both electron lucent and electron dense lipid droplets are
      present in the vitellocytes of C. truncatus, whereas only electron dense lipids
      occur in D. olrikii. A single lipid droplet turns up occasionally in the nuclei
      of some of the vitellocytes of C. truncatus. The ultrastructural features of
      vitellogenesis in spathebothriideans resemble those reported previously in
      "lower" cestodes, especially in pseudophyllideans.

PMID- 15940522
TI  - Influence of the long-term Trypanosoma cruzi infection in vertebrate host on the
      genetic and biological diversity of the parasite.
AB  - The influence of the long-term Trypanosoma cruzi infection in vertebrate host on
      the biological and genetic properties of the parasite was evaluated. Four T.
      cruzi isolates obtained from different chronic chagasic dogs infected with
      Berenice-78 T. cruzi strain during 2 and 7 years were comparatively analyzed. The
      long-term T. cruzi infection has led to alterations in parasitemia, virulence and
      pathogenicity of Be-78 strain for mice. These biological parameters varied from
      low to high in realation to the parental strain. Randomly amplified polymorphic
      DNA and isoenzyme profiles detected two distinct genetic groups of parasites. The
      first group included the parental strain and two T. cruzi isolates, and the
      second group the two other isolates. Interestingly, the isolates of the second
      group showed a reversibility of the genetic profile to the parental strain after
      25 passages in mice. No correlation between the genetic groups and biological
      properties of the isolates was observed. Our findings confirmed the population
      heterogeneity of the Be-78 strain, and showed how differently it responds to the
      long-term infection in the same vertebrate hosts.

PMID- 15940523
TI  - Genotype of Giardia intestinalis isolates from children and dogs and its
      relationship to host origin.
AB  - The presence of human Giardia in several animals suggests a zoonotic
      transmission. We studied G. Intestinalis isolates obtained from: children with
      diarrhea (n=6), asymptomatic children (n=7), axenic cultures (n=7) and dogs
      (n=11). The sequence corresponding to 16 S rRNA was amplified by PCR, sequenced
      and compared with genotypes A, B and Dog sequences reported in the Gene Bank
      database. Results show that 9/20 (45%) of children isolates belonged to genotype
      A and 11/20 (55%) showed some variable sites, allowing classification in three
      arbitrary clusters: A1, A2 and A3. In addition 7/11 (63%) of dog isolates were
      genotype A, including those dogs that lived in the same locality as the children
      lived, while 4/11 (37%) belonged to an arbitrary A4 cluster living in a different
      locality. In this study, genotype A was associated with samples from children and
      dogs, and, therefore, we could infer zoonotic transmission as a way of getting
      the disease.

PMID- 15940524
TI  - Glycogen as a carbohydrate energy reserve in trophozoites of Giardia lamblia.
AB  - Although there is indirect evidence to suggest that glycogen is present in G.
      lamblia, to date it has not been purified and identified from this organism. In
      this study, a high molecular weight carbohydrate was purified and characterized
      and its physiological role as an energetic reserve was established. The
      monosaccharide constituents of the carbohydrate reserve were identified as
      glucose by two independent methods: thin layer chromatography and an enzymatic
      assay. The degree of branching of the molecule was evaluated by comparing its
      absorbance spectrum in the presence of lugol with spectra of standard solutions
      of glycogen and starch under the same conditions. The results strongly suggest
      that glycogen is present in G. lamblia and acts as an energy reserve in
      trophozoites of this organism.

PMID- 15940525
TI  - Prevalence and intensity of haemogregarine blood parasites and their mite vectors
      in the common wall lizard, Podarcis muralis.
AB  - We describe the general field population biology of haemogregarines and mites in
      the wall lizard, Podarcis muralis, examining the factors that determine the
      prevalence and intensity of infection. The intensity of infection by
      haemogregarines in females was slightly lower in summer than in spring, whereas
      males maintained similar levels of intensity among all the seasons, probably due
      to immunosuppressive effects of testosterone. This is also supported because the
      prevalence and the infection intensity by mites were higher in males than in
      females. Parasite load was higher in lizards with better body condition, which
      could be reflecting the mortality of infected lizards with poor condition.

PMID- 15940526
TI  - Leucocytozoonosis in the Israeli sparrow, Passer domesticus biblicus Hartert
      1904.
AB  - Among the 91 house sparrows (Passer domesticus biblicus Hartert, 1904) examined
      and caught in the Jordan valley, Israel, 79% were found to be infected with
      Leucocytozoon fringillinarum Woodcock 1910. In the coastal plain of Israel (South
      of Tel Aviv), Leucocytozoon infection was found in only 3 out of 43 examined
      sparrows. In the birds examined, Leucocytozoon gametocytes were present, often in
      large numbers, in the circulating blood of the visceral organs, whereas they were
      only sporadic or even absent in the peripheral blood. Gametocytes were seen in
      the brain capillaries in only a few birds. Only one of the heavily infected
      sparrows was anemic. Leucocytozoon merozoites were present in the liver and
      kidneys in only a few infected birds. Merogonic infections did not induce any
      severe pathological changes, while the gametocyte congestion caused dilation of
      the blood vessels and sinuses. Tissue damage by the gametocyte parasitemia was
      most evident in the liver and kidneys. Leucocyte infiltration developed alongside
      the affected vessels; diffuse necrosis developed in the infiltrated areas. In the
      kidneys, many tubules were degenerated. Leucocytozoon gametocyte infection in
      sparrows is unique in that it appears to be confined, for most of its duration,
      to the visceral circulation, resulting in clinical consequences. Geographically,
      it is confined to habitats presumably supporting vectors.

PMID- 15940527
TI  - Plant regeneration from protoplasts isolated from embryogenic suspension cultured
      cells of Cinnamomum camphora L.
AB  - An efficient and reproducible protocol is described for the regeneration of
      Cinnamomum camphora protoplasts isolated from cultured embryogenic suspension
      cells. Maximum protoplast yield (13.1+/-2.1x10(6)/g FW) and viability (91.8+/
      3.8%) were achieved using a mixture of 3% (w/v) cellulase Onozuka R10 and 3%
      (w/v) macerozyme Onozuka R10 in 12.7% (w/v) mannitol solution containing 0.12%
      (w/v) MES, 0.36% (w/v) CaCl(2).2H(2)O, and 0.011% (w/v) NaH(2)PO(4).2H(2)O. First
      divisions occurred 7-10 days following culture initiation. The highest division
      frequency (24.6+/-2.9%) and plating efficiency (6.88+/-0.8%) were obtained in
      liquid medium (MS) supplemented with 30 g l(-1) sucrose, 0.7M glucose, 0.1 mg l(
      1) NAA, 1.0 mg l(-1) BA, and 1.0 mg l(-1) GA(3). After somatic embryo induction
      and then shoot induction, the protoplast-derived embryos produced plantlets at an
      efficiency of 17.5%. Somatic embryos developed into well-rooted plants on MS
      medium supplemented with 1.0 mg l(-1) 3-indole butyric acid (IBA). Regenerated
      plants that transferred to soil have normal morphology.

PMID- 15940528
TI  - Comparison of four constitutive promoters for the expression of transgenes in the
      tropical nitrogen-fixing tree Allocasuarina verticillata.
AB  - Allocasuarina verticillata is an actinorhizal tree that lives in symbiotic
      association with a nitrogen fixing actinomycete called Frankia. In the search for
      promoters that drive strong constitutive expression in this tropical tree, we
      studied the organ specificity of four different constitutive promoters (CaMV 35S,
      e35S, e35S-4ocs and UBQ1 from Arabidopsis thaliana) in stably transformed A.
      verticillata plants. The ss-glucuronidase (gus) gene was used as a reporter and
      expression studies were carried out by histochemical analyses on shoots, roots
      and actinorhizal nodules. While the 35S promoter was poorly expressed in the
      shoot apex and lateral roots, both the e35S and e35S-4ocs were found to drive
      high constitutive expression in the transgenic non-nodulated plants. In contrast,
      the UBQ1 promoter was very poorly expressed and appeared unsuitable for A.
      verticillata. We also showed that none of the promoters studied were active in
      the nodule infected cells, whatever the developmental stage studied.

PMID- 15940529
TI  - Endovascular treatment of an "anterior cerebral artery" aneurysm in a patient
      with "embryonic unfused middle cerebral artery" anomaly: a case report.
AB  - We report a unique case of an anterior cerebral artery aneurysm in a patient with
      embryonic unfused middle cerebral artery anomaly. The arterial twigs of the
      middle cerebral artery supply the entire middle cerebral artery territory
      including the lenticulostriate branches. There was a vessel incorporated into the
      aneurysm, which was referred to as an accessory middle cerebral artery and it
      gave rise to a lenticulostriate branch. The aneurysm was occluded with detachable
      coils using a remodeling technique. After successful occlusion of the aneurysm
      the so-called accessory middle cerebral artery including its lenticulostriate
      branch started to fill from the anomalous middle cerebral artery network and the
      patient did not experience any ischemic injury.

PMID- 15940530
TI  - Primary lymphoma of the skull base.
AB  - This case demonstrates the rare finding of a primary malignant lymphoma of the
      frontobasis and ethmoidal cells in a patient presenting with progressive loss of
      vision. Computed tomography and MRI demonstrated a homogenously enhancing tumour
      with extensive bony destructions of the skull base. After transsphenoidal biopsy,
      histology revealed a highly malignant primary B-cell lymphoma. The patient was
      further treated with immunochemotherapy. Tissue diagnosis is, therefore, crucial
      before a definitive therapy is instituted.

PMID- 15940531
TI  - Utilisation of medications recommended for chronic heart failure and the
      relationship with annual hospitalisation duration in patients over 75 years of
      age. A pharmacoepidemiological study.
AB  - OBJECTIVES: Trials in chronic heart failure (CHF) include few patients older than
      75 years, who represent a large proportion of CHF patients. We evaluated the
      influence of age on CHF-medication use and of CHF medications on hospitalisation
      in patients older than 75 years. METHODS: Included in our nested case-control
      study were 281 patients admitted in 2000 to a French teaching hospital with a
      main diagnosis of CHF and monitored over a 12-month period. Patient
      characteristics, medications at discharge, outpatient medications and
      hospitalisation frequency and duration were compared by means of univariate and
      multivariate analyses. RESULTS: Patients older than 75 years (n=150) and 75 years
      or younger (n=131) were similar with regard to NYHA class and ejection fraction.
      At discharge, diuretic use was similar in the two groups, but fewer older
      patients were prescribed angiotensin-converting enzyme (ACE) inhibitors (48%
      versus 63%, P<0.01) or beta-blockers (19% versus 37%, P<0.001). During follow-up,
      total re-admission rate and mean number of re-admissions were similar; however,
      total hospitalisation duration was greater in patients older than 75 years (38+/
      77 days) than in those 75 years or younger (26+/-59 days) (P<0.01). In patients
      over 75 years, shorter 12-month hospitalisation duration was associated with
      prescription of diuretics (P<0.001), ACE inhibitors (P<0.001), beta-blockers
      (P<0.01) and digitalis (P<0.05). CONCLUSIONS: Recent advances in CHF therapy are
      generally applied less to patients over 75 years of age-associated with longer
      annual hospitalisation duration in this population. Appropriate CHF medications
      at hospital discharge appear to reduce annual hospitalisation duration in
      patients older than 75 years.

PMID- 15940532
TI  - Animal models of premature and retarded ejaculation.
AB  - Most of our current understanding of the neurobiology of sexual behavior and
      ejaculatory function has been derived from animal studies using rats with normal
      sexual behaviour. However, none of these proposed models adequately represents
      human ejaculatory disorders. Based on the "ejaculation distribution theory",
      which postulates that the intravaginal ejaculation latency time in men is
      represented by a biological continuum, we have developed an animal model for the
      research of premature and delayed ejaculation. In this model, a large number of
      male Wistar rats are investigated during 4-6 weekly sexual behavioural tests.
      Based on the number of ejaculations during 30 min tests, rapid and sluggish
      ejaculating rats are distinguished, each representing approximately 10% at both
      ends of a Gaussian distribution. Together with other parameters, such as
      ejaculation latency time, these rats at either side of the spectrum resemble men
      with premature and delayed ejaculation, respectively. Comparable to the human
      situation, in a normal population of rats, endophenotypes exist with regard to
      basal sexual (ejaculatory) performance.

PMID- 15940533
TI  - Cardiorespiratory synchronization during Zen meditation.
AB  - The impact of meditation on cardiorespiratory synchronization with respect to
      breathing oscillations and the modulations of heart rate induced by respiration
      (respiratory sinus arrhythmia, RSA) was investigated in this study. Four
      different exercises (spontaneous breathing, mental task, Zen meditation, and
      Kinhin meditation) were consecutively performed by nine subjects mainly without
      any experience in meditation. An electrocardiogram and a respiratory trace were
      recorded simultaneously. On this basis the degree of cardiorespiratory
      synchronization was quantified by a technique which has been adopted from the
      analysis of weakly coupled chaotic oscillators. Both types of meditation showed a
      high degree of synchronization, whereas heartbeat and respiration were hardly
      synchronized during spontaneous breathing. During the mental task exercise the
      extent of synchronization was slightly higher than during spontaneous breathing.
      These results were largely determined by the breathing frequency because the two
      types of meditation induce low breathing frequencies which led to a pronounced
      and in-phase RSA. During the meditation the low breathing frequencies led to a
      decrease in the high frequency of heart rate variability, whereas the low
      frequency and the extent of RSA increased. The heart rate primarily reflected the
      degree of physical effort. The high degree of cardiorespiratory synchronization
      during meditation in unexperienced meditators suggests that the physiological
      implications of meditation does not require prior experience in meditation.

PMID- 15940534
TI  - Sleep disturbance at simulated altitude indicated by stratified respiratory
      disturbance index but not hypoxic ventilatory response.
AB  - At high altitudes, the clinically defined respiratory disturbance index (RDI) and
      high hypoxic ventilatory response (HVR) have been associated with diminished
      sleep quality. Increased RDI has also been observed in some athletes sleeping at
      simulated moderate altitude. In this study, we investigated relationships between
      the HVR of 14 trained male endurance cyclists with variable RDI and sleep quality
      responses to simulated moderate altitude. Blood oxygen saturation (SpO2%), heart
      rate, RDI, arousal rate, awakenings, sleep efficiency, rapid eye movement (REM)
      sleep, non-REM sleep stages 1, 2 and slow wave sleep as percentages of total
      sleep time (%TST) were measured for two nights at normoxia of 600 m and one night
      at a simulated altitude of 2,650 m. HVR and RDI were not significantly correlated
      with sleep stage, arousal rate or awakening response to nocturnal simulated
      altitude. SpO2 was inversely correlated with total RDI (r = -0.69, P = 0.004) at
      simulated altitude and with the change in arousal rate from normoxia (r = -0.65,
      P = 0.02). REM sleep response to simulated altitude correlated with the change,
      relative to normoxia, in arousal (r = -0.63, P = 0.04) and heart rate (r = -0.61,
      P = 0.04). When stratified, those athletes at altitude with RDI >20 h(-1) (n = 4)
      and those with <10 h(-1) (n = 10) exhibited no difference in HVR but the former
      had larger falls in SpO2 (P = 0.05) and more arousals (P = 0.03). Neither RDI
      (without stratification) nor HVR were sufficiently sensitive to explain any
      deterioration in REM sleep or arousal increase. However, the stratified RDI
      provides a basis for determining potential sleep disturbance in athletes at
      simulated moderate altitude.

PMID- 15940535
TI  - The basic reproductive number of tick-borne encephalitis virus. An empirical
      approach.
AB  - Tick-borne encephalitis virus (TBEV) is reciprocally transmitted between Ixodes
      ricinus ticks and small mammals. Recently, transmission between co-feeding ticks
      has been postulated as an epidemiological by important mechanism of perpetuating
      the agent. To empirically examine the question whether the "traditional" mode of
      transmission is sufficient to maintain enzootic TBEV transmission, the basic
      reproductive number R(0) of TBEV could be estimated under this model for sites in
      which TBEV is enzootic. I propose an empirical estimator of R(0) for TBEV which
      is based on longitudinal stage-specific local tick infestation densities assessed
      by live trapping of small mammals. A Gibbs sampler-based 95%-credibility interval
      is presented. When applied to published field data from TBEV enzootic sites sub
      critical R(0) estimates are obtained for both sites. I discuss potential
      shortcomings of this method and possible implications of these findings on the
      discussion of supplemental mechanisms of transmission.

PMID- 15940536
TI  - Eye movement instabilities and nystagmus can be predicted by a nonlinear dynamics
      model of the saccadic system.
AB  - The study of eye movements and oculomotor disorders has, for four decades,
      greatly benefitted from the application of control theoretic concepts. This paper
      is an example of a complementary approach based on the theory of nonlinear
      dynamical systems. Recently, a nonlinear dynamics model of the saccadic system
      was developed, comprising a symmetric piecewise-smooth system of six first-order
      autonomous ordinary differential equations. A preliminary numerical investigation
      of the model revealed that in addition to generating normal saccades, it could
      also simulate inaccurate saccades, and the oscillatory instability known as
      congenital nystagmus (CN). By varying the parameters of the model, several types
      of CN oscillations were produced, including jerk, bidirectional jerk and pendular
      nystagmus. The aim of this study was to investigate the bifurcations and
      attractors of the model, in order to obtain a classification of the simulated
      oculomotor behaviours. The application of standard stability analysis techniques,
      together with numerical work, revealed that the equations have a rich bifurcation
      structure. In addition to Hopf, homoclinic and saddlenode bifurcations organised
      by a Takens-Bogdanov point, the equations can undergo nonsmooth pitchfork
      bifurcations and nonsmooth gluing bifurcations. Evidence was also found for the
      existence of Hopf-initiated canards. The simulated jerk CN waveforms were found
      to correspond to a pair of post-canard symmetry-related limit cycles, which exist
      in regions of parameter space where the equations are a slow-fast system. The
      slow and fast phases of the simulated oscillations were attributed to the
      geometry of the corresponding slow manifold. The simulated bidirectional jerk and
      pendular waveforms were attributed to a symmetry invariant limit cycle produced
      by the gluing of the asymmetric cycles. In contrast to control models of the
      oculomotor system, the bifurcation analysis places clear restrictions on which
      kinds of behaviour are likely to be associated with each other in parameter
      space, enabling predictions to be made regarding the possible changes in the
      oscillation type that may be observed upon changing the model parameters. The
      analysis suggests that CN is one of a range of oculomotor disorders associated
      with a pathological saccadic braking signal, and that jerk and pendular nystagmus
      are the most probable oscillatory instabilities. Additionally, the transition
      from jerk CN to bidirectional jerk and pendular nystagmus observed experimentally
      when the gaze angle or attention level is changed is attributed to a gluing
      bifurcation. This suggests the possibility of manipulating the waveforms of
      subjects with jerk CN experimentally to produce waveforms with an extended
      foveation period, thereby improving visual resolution.

PMID- 15940537
TI  - Species coexistence and periodicity in host-host-pathogen models.
AB  - Models for the transmission of an infectious disease in one and two host
      populations with and without self-regulation are analyzed. Many unusual behaviors
      such as multiple positive equilibria and periodic solutions occur in previous
      models that use the mass-action (density-dependent) incidence. In contrast, the
      models formulated using the frequency-dependent (standard) incidence have the
      behavior of a classic endemic model, since below the threshold, the disease dies
      out, and above the threshold, the disease persists and the infectious fractions
      approach an endemic equilibrium. The results given here reinforce previous
      examples in which there are major differences in behavior between models using
      mass-action and frequency-dependent incidences.

PMID- 15940538
TI  - Kinetic models for chemotaxis: hydrodynamic limits and spatio-temporal
      mechanisms.
AB  - We study kinetic models for chemotaxis, incorporating the ability of cells to
      assess temporal changes of the chemoattractant concentration as well as its
      spatial variations. For prescribed smooth chemoattractant density, the
      macroscopic limit is carried out rigorously. It leads to a drift equation with a
      chemotactic sensitivity depending on the time derivative of the chemoattractant
      density. As an application it is shown by numerical experiments that the new
      model can resolve the chemotactic wave paradox. For this purpose, the macroscopic
      equation is coupled to a simple activation-inhibition model for the
      chemoattractant which produces the chemoattractant waves typical for the slime
      mold Dictyostelium discoideum.

PMID- 15940539
TI  - Dynamical behaviour of epidemiological models with sub-optimal immunity and
      nonlinear incidence.
AB  - In this paper we analyze the dynamics of two families of epidemiological models
      which correspond to transitions from the SIR (susceptible-infectious-resistant)
      to the SIS (susceptible-infectious-susceptible) frameworks. In these models we
      assume that the force of infection is a nonlinear function of density of
      infectious individuals, I. Conditions for the existence of backwards
      bifurcations, oscillations and Bogdanov-Takens points are given.

PMID- 15940540
TI  - General mathematical frame for open or closed biomembranes (Part I): equilibrium
      theory and geometrically constraint equation.
AB  - This paper aims at constructing a general mathematical frame for the equilibrium
      theory of open or closed biomembranes. Based on the generalized potential
      functional, the equilibrium differential equation for open biomembrane (with free
      edge) or closed one (without boundary) is derived. The boundary conditions for
      open biomembranes are obtained. Besides, the geometrically constraint equation
      for the existence, formation and disintegration of open or closed biomembranes is
      revealed. The physical and biological meanings of the equilibrium differential
      equation and the geometrically constraint equation are discussed. Numerical
      simulation results for axisymmetric open biomembranes show the effectiveness and
      convenience of the present theory.

PMID- 15940541
TI  - Ecological conditions that favor the evolution of intermediate-virulence in an
      environmentally transmitted parasite.
AB  - In this paper we develop and analyze several population-dynamic models of an
      environmentally transmitted symbiotic parasite infecting an isolated population
      of susceptible hosts. In our most basic model infection acts only to decrease the
      average lifetime of the infected host, parasites are only transmitted to
      uninfected hosts, there is no recovery from infection, and the rate of parasite
      transmission is an increasing function of the level of parasite virulence. It is
      shown that invasion of the parasite-free equilibrium cannot occur for virulence
      levels that are either too high or too low. We then incorporate a number of
      modifications to the model, among them the possibility that host fertility is
      reduced by infection, and that transmission rate depends additionally on
      susceptible host density. It is shown that the essential nature of the conditions
      for invasion are preserved. Thus, natural selection for intermediate virulence is
      a generic property of a broad class of population models.

PMID- 15940542
TI  - Entanglement invariants and phylogenetic branching.
AB  - It is possible to consider stochastic models of sequence evolution in
      phylogenetics in the context of a dynamical tensor description inspired from
      physics. Approaching the problem in this framework allows for the well developed
      methods of mathematical physics to be exploited in the biological arena. We
      present the tensor description of the homogeneous continuous time Markov chain
      model of phylogenetics with branching events generated by dynamical operations.
      Standard results from phylogenetics are shown to be derivable from the tensor
      framework. We summarize a powerful approach to entanglement measures in quantum
      physics and present its relevance to phylogenetic analysis. Entanglement measures
      are found to give distance measures that are equivalent to, and expand upon,
      those already known in phylogenetics. In particular we make the connection
      between the group invariant functions of phylogenetic data and phylogenetic
      distance functions. We introduce a new distance measure valid for three taxa
      based on the group invariant function known in physics as the "tangle". All work
      is presented for the homogeneous continuous time Markov chain model with
      arbitrary rate matrices.

PMID- 15940543
TI  - Overeruption without root exposure of third molars and periodontal health in the
      mandible.
AB  - Bone formation is seen around the third molar even when the tooth is exposed to
      the oral environment due to overeruption. To determine if overeruption of the
      third molar with or without root exposure is related to the status of the
      exposure of other teeth in the mandible, using orthopantomographs, 424 third
      molars were studied in 371 patients who were over 41 years of age. The rate of
      overeruption and root exposure in third molars was measured, and its relationship
      to the number of teeth lost and the rate of root exposure in other teeth in the
      mandible was analyzed. Tooth loss in the group of third molars with overeruption
      without root exposure was greater than in that without overeruption or root
      exposure in men, whereas the relationship was not seen in women. We found that
      root exposures of other teeth in the group of third molars with overeruption
      without root exposure were significantly smaller than in those with root exposure
      in both genders. Third molars with overeruption without root exposure, in which
      bone formation was easy to observe for radiographic diagnosis, were correlated
      with periodontal health in the mandible, suggesting a component of precision
      determination for predicting resistance to periodontitis.

PMID- 15940544
TI  - MRI detection of atrophic kidney in a hypertensive child with a single kidney.
AB  - The role of magnetic resonance imaging (MRI) in the work-up of secondary causes
      of pediatric hypertension is typically restricted to that of renovascular causes
      where main renal artery stenosis is suspected. We report a case of a 10-year-old
      female child with hypertension, who was thought to have unilateral renal
      agenesis, because only a solitary left kidney could be visualized on both
      ultrasound and renal scintigraphy. Our patient underwent magnetic resonance
      imaging because of suspected renal artery stenosis in her solitary left kidney.
      At MRI she was found to have a normal left kidney. However, a very tiny, atrophic
      right kidney was also visualized. A laparoscopic right nephrectomy was performed,
      which resulted in complete resolution of her hypertension. This case illustrates
      a possible additional role for MRI in a very small subset of pediatric
      hypertensive patients: those with a single kidney on ultrasound.

PMID- 15940545
TI  - Impaired neutrophils in children with the typical form of hemolytic uremic
      syndrome.
AB  - Experimental and clinical evidence suggest that activated neutrophils (PMN) could
      contribute to endothelial damage in Hemolytic Uremic Syndrome (D+HUS).
      Additionally, while PMN-activating cytokines and PMN-derived products have been
      found in D+HUS sera, we have demonstrated phenotypic alterations in D+HUS PMN
      compatible with a deactivation state. Here, we investigated whether D+HUS PMN
      were actually hyporesponsive, and explored some of the mechanisms probably
      involved in their derangement. Twenty-two D+HUS children were bled in the acute
      period, and blood samples from healthy, acute uremic and neutrophilic children
      were obtained as controls. We evaluated degranulation markers in response to
      cytokines, intracellular granule content, and reactive oxygen species (ROS)
      generation in circulating D+HUS and control PMN. The influence of D+HUS-derived
      plasma and the direct effects of Stx in vitro were evaluated on healthy donors'
      PMN. We found that D+HUS PMN presented reduced degranulatory capacity in response
      to cytokines and intracellular granule content, and decreased ROS generation.
      D+HUS plasma or Stx did not affect the phenotype and function of healthy donors'
      PMN. These results suggest that upon hospitalization D+HUS PMN are functionally
      impaired and show features of previous degranulation, indicating a preceding
      process of activation with release of ROS and proteases involved in endothelial
      damage.

PMID- 15940546
TI  - Epidemiology treatment and outcome of childhood systemic lupus erythematosus in
      Egypt.
AB  - To highlight the characteristics of Egyptian children with systemic lupus
      erythematosus (SLE), the records of 52 SLE patients (48 girls and four boys aged
      11.9+/-2.6 years) were retrospectively analyzed. The median duration of follow up
      was 22 months (range 1-94.5). The most common extrarenal manifestation was fever
      (76.6%), followed by joint involvement (65.4%). Hemolytic anemia was demonstrated
      in 51%, thrombocytopenia in 29.2%, and leucopenia in 27.5%. Antinuclear
      antibodies were positive in 92.7%, while positive anti-double-stranded DNA and
      hypocomplementemia were demonstrated in 95.6% and 67.4%, respectively. Lupus
      nephritis (LN) was evident in 80.8%. The renal manifestations of LN patients were
      proteinuria (83.3%), hematuria (71.5%), hypertension (35.7%), and elevated serum
      creatinine (16.7%). The histopathological findings of the initial renal biopsies
      were class I (4.9%), class II (22%), class III (36.3%), and class IV (36.3%).
      Among patients without LN, 85.7% gained remission and nonimmediately died. At
      last observation, 55.6% of LN patients had complete remission, 22.2% had active
      disease, and 22.2% died. Most patients who died had class IV LN. In conclusion,
      the characteristics of Egyptian SLE children are comparable with those in most
      Arab and Western series. However, LN may be more prevalent and severe, with
      unfavorable outcomes.

PMID- 15940547
TI  - A nephrotic child with deep vein thrombosis after a long-haul flight.

PMID- 15940548
TI  - Childhood thin GBM disease: review of 22 children with family studies and long
      term follow-up.
AB  - Thin glomerular basement membrane (GBM) disease is generally known to have a good
      renal prognosis, although renal insufficiency has sometimes been reported and the
      overlap with Alport syndrome implies that a good prognosis cannot be guaranteed.
      In order to shed light on long-term prognosis of thin GBM disease we have
      retrospectively evaluated 22 children with persistent haematuria and biopsy
      proven thin GBM. Mean follow up was 7 years (range 2-17 years), mean age at onset
      was 7 years (range 1.5-15). Biopsies were performed a mean of 3.8 years after
      detection of hematuria. The light microscopy (LM) and immunofluorescence (IF)
      findings were essentially unremarkable in all of the children, while electron
      microscopy (EM) showed thinning of the GBM in all cases and no changes
      characteristic of Alport syndrome. The family history was positive for renal
      disease in 17 (77.3%) patients with hematuria in 8 (36.3%) families, and
      hematuria with renal failure (RF) or deafness in 9 (40.9%). It was completely
      negative for renal disease in 4 (18.2%) and unavailable in 1 (4.5%). Four
      patients (18%) showed a decline in renal function after 6, 8, 9 and 12 years of
      follow-up, and 1 of these also developed hearing impairment. None developed
      hypertension. Our study suggests that thin GBM disease is not always benign and a
      child with thin GBM should never be assigned such a prognosis, especially if
      there is a family history of renal impairment or deafness, where careful follow
      up is needed due to the risk of late onset renal failure.

PMID- 15940550
TI  - Gamma-tubulin and microtubule organization during microsporogenesis in Ginkgo
      biloba.
AB  - This is the first report on gamma-tubulin and microtubule arrays during
      microsporogenesis in a gymnosperm. Meiosis in Ginkgo biloba is polyplastidic, as
      is typical of the spermatophyte clade, and microtubule arrays are organized at
      various sites during meiosis and cytokinesis. In early prophase, a cluster of
      gamma-tubulin globules occurs in the central cytoplasm adjacent to the off-center
      nucleus. These globules diminish in size and spread over the surface of the
      nucleus. A system of microtubules focused on the gamma-tubulin forms a reticulate
      pattern in the cytoplasm. As the nucleus migrates to the center of the
      microsporocyte, gamma-tubulin becomes concentrated at several sites adjacent to
      the nuclear envelope. Microtubules organized at these foci of gamma-tubulin give
      rise to a multipolar prophase spindle. By metaphase I, the spindle has matured
      into a distinctly bipolar structure with pointed poles. In both first and second
      meiosis, gamma-tubulin becomes distributed throughout the metaphase spindles, but
      becomes distinctly polar again in anaphase. In telophase I, gamma-tubulin moves
      from polar regions to the proximal surface of chromosome groups/nuclei where
      interzonal microtubules are organized. No cell wall is deposited and the
      interzonal microtubules embrace a plate of organelles between the two nuclear
      cytoplasmic domains (NCDs) of the dyad. Following second meiosis, phragmoplasts
      that form between sister and non-sister nuclei fuse to form a complex six-sided
      structure that directs simultaneous cytokinesis. Gamma-tubulin becomes associated
      with nuclei after both meiotic divisions and is especially conspicuous in the
      distal hemisphere of each young microspore where an unusual encircling system of
      cortical microtubules develops.

PMID- 15940551
TI  - Rheumatoid arthritis in a patient with common variable immunodeficiency:
      difficulty in diagnosis and therapy.
AB  - Common variable immunodeficiency (CVID) is the most frequent primary
      immunodeficiency syndrome in adults with equal sex prevalence. The syndrome
      typically presents as recurrent infections, with onset in childhood or young
      adulthood (between 20 and 30 years). CVID patients also have a higher prevalence
      of autoimmune diseases. A 38-year-old woman presented to the Rheumatology
      Department with polyarthralgia and fever of 39 degrees C of several months'
      duration. She had recurrent respiratory and gastrointestinal tract infections and
      pernicious anemia. Immunological studies showed decreased levels of IgG, IgM,
      complete IgA deficiency, increased percentage of CD8 lymphocytes, and a reduced
      CD4:CD8 ratio. HLA-DR typing was performed and we identified HLA-DRB1*01.
      Adequate intravenous immune globulin substitution as well as antibiotic and anti
      inflammatory treatment resulted in the remission of arthritis. Hand radiograms
      repeated after 12 months showed narrowing of the intra-articular space in the
      right metacarpophalangeal and radiocarpal joints with multiple bone cysts and
      erosions. Erosions were found in both humeral heads as well. This prompted the
      diagnosis of rheumatoid arthritis. Arthritis can be a presenting symptom of
      primary immunodeficiency in adults, especially when accompanied by recurrent
      infections or autoimmune diseases. These patients require more advanced
      diagnostic procedures and therapeutic cooperation of different specialists.

PMID- 15940552
TI  - Have traditional DMARDs had their day? Effectiveness of parenteral gold compared
      to biologic agents.
AB  - This review tries to answer the question of whether in the face of the recently
      introduced biologics conventional disease-modifying antirheumatic drugs (DMARDs)
      can still be recommended in the treatment of rheumatoid arthritis (RA). We start
      with an overview of the oldest conventional DMARD, injectable gold (Au), which
      was introduced in the treatment of RA in the 1920s. The effect of gold is
      directed at a number of different sites of the immune system. A significant
      improvement of clinical and biochemical disease activity parameters as well as an
      inhibition of X-ray progression has been shown in many studies. Head-to-head
      comparisons between gold and high-dose methotrexate (MTX) demonstrated no
      significant difference but some advantages for gold. Since trials comparing
      biologics with gold will never be performed, an indirect comparison was done by
      analyzing the results of trials with gold with those with biologics. Conclusions
      from such comparisons have to be drawn with caution especially since the
      methodology for performing trials has changed with time. We selected four trials
      with gold (two open, one placebo-controlled, and one comparison with MTX) and
      five trials with biologics (three placebo-controlled, one dose escalation study,
      and one comparison with MTX). In all these trials baseline data regarding swollen
      joint count (SJC), erythrocyte sedimentation rate (ESR), and C-reactive protein
      (CRP) were roughly comparable and, with the exception of interleukin (IL)-1 RA,
      demonstrated a similar improvement of over 50% already after 6 months [with
      faster onset with tumor necrosis factor (TNF)-alpha blockade]. American College
      of Rheumatology (ACR) response data were not available for the older gold trials.
      European League Against Rheumatism (EULAR) response criteria could be calculated
      for the Au/MTX trial and were-for these compounds-only slightly inferior to the
      results with adalimumab. X-ray response is especially difficult to compare across
      studies. Although an inhibition with Au and MTX could be demonstrated, this
      occurred-similar to corticosteroid treatment-earlier and more pronounced with TNF
      alpha blockers. We confirm the statement of Weinblatt that the most modern DMARDs
      do not appear to be much better than the oldest one indicating that conventional
      DMARDs are not outdated. Therefore, a sufficient trial of conventional DMARDs
      should precede the introduction of treatment with the very expensive biologics.

PMID- 15940553
TI  - Prevalence of rheumatoid arthritis in Antalya, Turkey.
AB  - The aim of this study was to evaluate the prevalence of rheumatoid arthritis (RA)
      in Antalya, Turkey. A cross-sectional study was performed face-to-face using a
      structured interview. Subjects were asked whether they had arthritis at present
      or previously. Subjects suspected of having RA were invited to the hospital for
      physical examination and laboratory investigations. Diagnosis of RA was confirmed
      if the patient fulfilled 1987 American College of Rheumatology (ACR) criteria for
      RA. A total of 3173 subjects were interviewed. The diagnosis of RA was
      established in 12 subjects. The prevalence of RA was determined as 0.38% [95%
      confidence interval (CI): 0.16-0.59]. The mean age was 49.92+/-11.56 years in
      subjects with RA and greater than that of other subjects (p<0.001). Of 12
      subjects with RA, 9 had previously been diagnosed with the disease. Rheumatoid
      factor was detected in the sera of eight subjects. RA is less frequent in Turkey
      than in Northern Europe. Different genetic and environmental factors may have a
      role in this result.

PMID- 15940554
TI  - Intra- and interobserver variability of Kleerekoper's method in vertebral
      fracture assessment.
AB  - Radiographically detected vertebral fractures (VF) are a hallmark of
      osteoporosis. Several approaches to describe VF have been proposed. The objective
      of this study was to evaluate the intra- and interobserver variability of
      semiquantitative Kleerekoper's method in osteoporotic VF assessment. Sixty-seven
      postmenopausal osteoporotic (L2-4 T-score < or =-2.5) women with a mean age of
      65.2+/-7.51 years were included into the study. Lateral radiographs of thoracic
      and lumbar spine were evaluated in all patients. Kleerekoper's method was used to
      define VF. Two observers evaluated all radiographs independently. To investigate
      intraobserver reproducibility, the first observer reevaluated all radiographs a
      month later on a separate occasion. Intra- and interobserver agreement was
      calculated using the kappa statistic. The agreement between two readings for the
      first observer was 86.3% with a corresponding kappa score of 0.573 (95%
      confidence limits of kappa score were 0.505-0.642). Interobserver agreement was
      87.7% with a corresponding kappa score of 0.660 (95% confidence limits were 0.602
      0.718). We observed a moderate agreement for Kleerekoper's method in vertebral
      fracture assessment. There is no gold standard or standardized measurement or
      description for VF. Quantitative assessment of VF is essential in epidemiologic
      studies and in clinical drug trials, but a semiquantitative technique, which is
      done by experienced observers, should also be added to evaluate the entire
      spectrum of visible features that are helpful in identifying deformities.

PMID- 15940555
TI  - Clinical significance of antinucleosome antibodies in Tunisian systemic lupus
      erythematosus patients.
AB  - The aim of this study was to investigate the clinical significance of
      antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE)
      patients. IgG antinucleosome antibodies were detected by a qualitative enzyme
      immunoassay (immunodot) in the sera of SLE patients at onset of disease. The
      patients were divided into two groups according to the result of the
      antinucleosome antibodies test: positive (group A) and negative (group B). The
      two groups were also evaluated for clinical and biological parameters. Of 84
      patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients
      negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome
      positive. The most common initial features were haematological disorders (80.1%)
      and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE
      patients, were more common in group A compared to group B (65 vs 38%) (p=0.04).
      The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher
      in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies
      were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We
      found a correlation between antinucleosome antibodies, nephritis and SLE disease
      activity. Therefore, the determination of circulating antinucleosome antibodies
      could be a useful parameter for early diagnosis and follow-up of SLE patients.

PMID- 15940556
TI  - Relationship between clinically detected joint swelling and effusion diagnosed by
      ultrasonography in elbow joints in patients with rheumatoid arthritis.
AB  - The aim of this study was to compare the relationship between clinically detected
      swelling and effusion diagnosed by ultrasonography (US) in elbow joints in
      patients with rheumatoid arthritis (RA). Fifty consecutive patients with RA
      entered the study and 20 healthy persons formed a control group. Altogether 100
      elbow joints of the RA patients and 40 of the controls were studied. All the
      clinical assessments were performed by one doctor and the US investigations by
      the other and they were blinded to each others results. In 77 elbow joints of the
      RA patients the clinical assessment and the US gave similar results, whereas they
      differed in the remaining 23 joints. The kappa coefficient between these
      investigations was 0.371. In the control group no elbow joint showed either
      swelling in the clinical assessment or effusion in the US investigation. The
      results of this study indicate that clinical assessment of swelling and
      evaluation of effusion by US in elbow joints in patients with RA show only fair
      agreement. Thus, US may improve the accuracy of diagnosis of synovitis in many
      cases in these patients.

PMID- 15940557
TI  - Serological screening for celiac disease in premenopausal women with idiopathic
      osteoporosis.
AB  - The aim of this study was to perform serological testing to screen for celiac
      disease (CD) among premenopausal women with idiopathic osteoporosis and to
      investigate the bone turnover in patients who are seropositive for CD. We studied
      89 premenopausal women with idiopathic osteoporosis. The serological screening
      protocol was based on a two-level evaluation. The first level consisted of
      determining serum level of IgA antigliadin antibodies (AGA). Subjects who were
      negative for IgA AGA were classified as not having CD, while samples testing
      positive for IgA AGA underwent a second level of the screening process. For the
      second level of screening, the serum IgA endomysial antibody (EMA) test was
      performed. Bone metabolism was evaluated by serum calcium (Ca), phosphorus,
      alkaline phosphatase, parathyroid hormone (PTH), 25 (OH) vitamin D, osteocalcin
      (OC), urinary deoxypyridinoline (dPD), and 24-h urinary calcium levels. Of the 89
      patients evaluated, 17 were found to have positive IgA AGA tests (19%) and 9 were
      found to be positive for EMA (10.11%). EMA-positive patients showed lower values
      of serum Ca (p<0.05) and 25 (OH) vitamin D (p<0.01) and significantly higher
      values of PTH (p<0.01) compared with the EMA-negative patients. The level of
      urinary dPD was found to be significantly higher in EMA-positive patients
      (p<0.05). The results of this study suggest that all patients with idiopathic
      osteoporosis should be screened for CD by measurement of EMA. Additionally, we
      believe that serological screening for CD and detection of such patients will
      allow determination of the most convenient treatment strategies for osteoporosis.

PMID- 15940558
TI  - High-dose azathioprine pulse therapy as a new treatment option in patients with
      active Wegener's granulomatosis and lupus nephritis refractory or intolerant to
      cyclophosphamide.
AB  - The objective of this study was to evaluate the feasibility and safety of high
      dose azathioprine pulse (HAP) therapy in the induction of remission in patients
      with active Wegener's granulomatosis (WG) or progressive lupus nephritis (LN)
      refractory to or intolerant of cyclophosphamide. Four patients with
      antineutrophil cytoplasmic antibody (ANCA)-associated WG and two patients with
      progressive LN were treated with HAP (1200-1800 mg) applied monthly as continuous
      intravenous infusions at 50 mg/h. Patients received a total of 50 courses of
      intravenous azathioprine (AZA) therapy. Disease activity was assessed using the
      Birmingham Vasculitis Activity Score (BVAS) and the Systemic Lupus Erythematosus
      Activity Index (SLEDAI). As only partial remission was induced in patients with
      progressive LN on this regimen, an additional 18 cycles were applied in these
      patients in which oral AZA at 100 mg/day in weeks 2 and 3 was added between two
      intravenous courses. A hereditary defect in thiopurine methyltransferase activity
      was excluded before initiation of treatment. High-dose azathioprine pulse and the
      intensified HAP treatment were well tolerated. Complete remission was achieved in
      two patients with WG suffering from three relapses of disease on application of 2
      6 courses of HAP. Remission was maintained for 16-24 months. The remaining two
      patients with WG were withdrawn after 2-3 courses due to unchanged disease
      activity. In two patients with LN, partial remission was noted on 6-9 courses of
      HAP; however, the patients relapsed despite therapy with methotrexate and
      mycophenolate mofetil. The intensified HAP regimen led to partial or complete
      remission in both LN patients which was confirmed by sequential renal biopsies.
      Our results suggest that HAP therapy represents a well-tolerated regimen in
      patients with active WG and LN intolerant of or refractory to cyclophosphamide.
      As partial or complete remission was observed in four of six patients, further
      studies seem warranted to assess clinical efficacy in these patients.

PMID- 15940559
TI  - Effects of shoulder arthroplasty and exercise in patients with rheumatoid
      arthritis.
AB  - The aim of this study was to examine pain and shoulder function in patients with
      rheumatoid arthritis (RA) before and after shoulder arthroplasty and
      postoperative exercise. Twenty-four patients (26 shoulders) were consecutively
      included in a multicentre study. Before surgery, at discharge from hospital and
      after 3 and 6 months, perceived shoulder function and shoulder pain were assessed
      by visual analogue scales, activities of daily living by the Modified Health
      Assessment Questionnaire (M-HAQ) and shoulder range of motion (ROM) by a
      goniometer. All patients showed considerable pain reduction at discharge from
      hospital (p<0.001). In those with intact rotator cuff and biceps tendon (n=13)
      improvements were found after 6 months in active and passive abduction and
      flexion ROMs (p<0.01) and in M-HAQ (p<0.001). Such improvements were not found in
      those with torn soft tissue (n=12). Preoperatively, abduction and flexion motor
      deficits (passive ROM >active ROM) were found for the total group (p=0.001). Less
      flexion motor deficit was found in the intact soft tissue than in the torn soft
      tissue group after 3 (p=0.002) and 6 months (p<0.001). No group difference was
      found with respect to abduction motor deficit. In conclusion, pain relief was
      obtained by all patients. Improvements in ROMs and activities of daily living
      were influenced by the state of the soft tissue.

PMID- 15940560
TI  - Ultrasonographic evaluation of tendons and enthesal sites in rheumatoid
      arthritis: comparison with ankylosing spondylitis and healthy subjects.
AB  - The objective of this study was to determine tendon involvements and enthesal
      abnormalities in patients with rheumatoid arthritis (RA) using high-resolution
      ultrasonographic images and to compare the findings with those seen in patients
      with ankylosing spondylitis (AS) and healthy controls. A total of 24 patients
      with RA, 18 with AS, and 20 healthy controls matched by age and body mass index
      (BMI) were included in the study. All of the patients and controls underwent
      clinical and ultrasonographic examinations of both lower limbs at five enthesal
      sites (superior and inferior pole of the patella, tibial tuberosity, Achilles
      tendon, and plantar aponeurosis) and both upper limbs at two tendon sites
      (tendons of m. biceps brachii and supraspinatus at the shoulder). High-resolution
      ultrasonographic examinations were performed to detect bursitis, structure
      thickness, bony erosion, and enthesophyte. An ultrasonographic score of lower
      limb enthesitis was calculated using the Glasgow Ultrasound Enthesitis Scoring
      System (GUESS) in all patients. Tendon involvements and enthesal abnormalities
      were found significantly more often in the RA group than in controls (p<0.05 to
      <0.001), but were not found to be different from the AS group (p>0.05). On
      clinical examination 67 of 336 (19.9%) tendon and enthesal sites were abnormal
      and on ultrasonographic examination 130 of 336 (38.2%) sites were abnormal in RA
      patients. The most frequently affected enthesal sites in the lower limbs were
      suprapatellar, infrapatellar, and Achilles tendon in both the RA and AS groups.
      The tibial tuberosity was less affected in both groups, and involvement of the
      plantar aponeurosis was not different from the controls. A statistically
      significant correlation was found between the Ritchie articular index and GUESS
      (r=0.578, p=0.008). Tendon involvements and enthesal abnormalities in RA patients
      were found more often than had been estimated. Further studies are required to
      validate our results.

PMID- 15940561
TI  - Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee
      osteoarthritis.
AB  - The cartilage oligometrix matrix protein (COMP) is a noncollagenous protein, a
      glycoprotein, the function of which is to bind to type II collagen fibres and
      stabilise the collagen fibre network in the articular cartilage. In the serum of
      the normal population the COMP level is 5 mug/ml. An increased level of COMP in
      the synovial fluid was described in the early stage of rheumatoid arthritis (RA),
      whereas in advanced stages of RA, the level of COMP decreased. In this study we
      assessed the serum COMP level in patients with RA and knee osteoarthritis (OA)
      and found a correlation between the serum COMP level and other markers as well as
      bone mass density (BMD) changes, activity of disease, disease duration and the
      age of the patients. The blood was collected from 30 RA patients and 30 OA
      patients who constituted the control group. The serum COMP level was determined
      using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value
      of the serum COMP level in RA patients was 10.4+/-3.6 U/l. There was a
      correlation between the serum COMP level and the age of RA patients (p<0.005) and
      disease activity score (DAS) value (p<0.01). According to correlation
      coefficients, the serum COMP level was independent of stage of disease, number of
      painful and swollen joints, duration of morning stiffness, disease duration and
      titre of the Waaler-Rose test. The influence of rheumatoid nodule presence on the
      serum COMP level was shown (p<0.05). In RA patients with erythrocyte
      sedimentation rate (ESR) values below 20 mm/h compared with patients with ESR
      values over 60 mm/h, the serum COMP level was observed to be significantly lower
      (p<0.05). The average value of COMP in OA patients was 10.4+/-2.7 U/l. No
      correlation was found between the serum COMP level and patients' age and disease
      duration. There was a correlation between the serum COMP level and Western
      Ontario and McMaster Universities (WOMAC) index pain scale for the lower limbs
      (p<0.005) and T-score value of densitometry examinations (p<0.036) in OA
      patients. No statistical differences were found between the average serum COMP
      level in RA and OA patients.

PMID- 15940562
TI  - ENT Wegener's granulomatosis can hide severe central nervous system involvement.
AB  - The clinical manifestations of localised or early systemic forms of Wegener's
      granulomatosis (WG) do not require immediate treatment to save the patient's life
      and/or the function of a vital organ. The organs mainly involved are the ear,
      nose, throat (ENT) and lung, and the results of antineutrophil cytoplasmic
      antibody (ANCA) assays are frequently negative. We here describe three cases of
      the ANCA-negative early systemic form of WG with prevalent ENT involvement
      complicated by severe central nervous system (CNS) disease; in two cases, the
      only symptom was a mild headache. We conclude that, although apparently mild, the
      localised and early systemic forms of WG can hide CNS involvement and may require
      immediate treatment. This complication should be suspected and investigated in
      the case of patients with localised or early systemic disease especially in the
      presence of ENT involvement and negative ANCA assays.

PMID- 15940563
TI  - Pleural amyloidosis as the first sign of IgD multiple myeloma.
AB  - We describe a case of IgD myeloma with amyloid and plasmocytic pleural
      localisations. At the onset of the disease it mimicked rheumatoid arthritis,
      which can be the first presentation of both AL amyloidosis and multiple myeloma.
      Pleural effusion can happen first in IgD myeloma, but our observation is of
      interest in that it confirms the very rare possibility of pleural amyloid and
      plasmocytic localisations devoid of pleural effusion.

PMID- 15940564
TI  - Shoulder hemarthrosis due to a bleeding pseudoaneurysm.
AB  - We describe a patient with advanced shoulder osteoarthritis who developed a
      spontaneous hemarthrosis due to a bleeding pseudoaneurysm. This rare cause of
      intra-articular hemorrhage is important to establish because specific treatment
      may offer relief and prevent further bleeding.

PMID- 15940565
TI  - Fracture of axial spinous process in a patient with rheumatoid arthritis.

PMID- 15940566
TI  - Prognostic factors of low bone mineral density in ankylosing spondylitis.

PMID- 15940567
TI  - Lupus erythematosus and sarcoidosis.

PMID- 15940568
TI  - Systemic sclerosis following oral contraception.

PMID- 15940570
TI  - [Concept and anatomical feasibility study of an "endosteal electrode" for bimodal
      stimulation in severely deaf ears].
AB  - BACKGROUND: Many patients with severe hearing loss could benefit from a bimodal
      stimulation unilaterally: acoustically in the apical region of the cochlea with
      some residual low frequency hearing and electrically via a cochlear implant in
      the basal turn with lost high hearing in the high frequency range. As a new
      concept we introduce the idea of an "endosteal electrode" - to be inserted
      between spiral ligament and endosteum of the bony wall without opening the fluid
      filled inner ear. In this paper the feasibility from the anatomical point of view
      is to be proven. MATERIALS AND METHODS: In 10 human temporal bone specimens the
      bone covering the membraneous inner ear is carefully removed in the site of a
      typical cochleostomy. It should by proven whether or not the soft tissue layer
      covering the inner ear could be left intact and, furthermore, whether a "dummy
      electrode array" could be inserted "endosteally". RESULTS: In 10 of the 10
      specimen the preparation could be carried out in the desired way, leaving the
      spiral ligament intact. The regular site of the "electrode" was morphologically
      proven after embedding the specimens for histological evaluation. CONCLUSIONS:
      From the anatomical point of view, an "endosteal cochlear implantation" seems
      feasible. Further experiments including animal studies must show, whether this
      concept might succeed functionally.

PMID- 15940569
TI  - Photodynamic inactivation of fibroblasts by a cationic porphyrin.
AB  - An important determinant of the clinical applicability and value of antimicrobial
      photodynamic inactivation (PDI) is the cytotoxicity of the treatment to human
      cells. We evaluated the in vitro cytotoxicity of PDI to human dermal fibroblasts
      using 5-phenyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin chloride (TriP[4]) as
      the photosensitiser. The fibroblasts were exposed to a PDI regime that is known
      to be sufficient for the inactivation of Staphylococcus aureus, Pseudomonas
      aeruginosa and Candida albicans. The PDI experiments were carried out in
      phosphate-buffered saline (PBS) and in 6.25%, 12.5%, 25% and 50% fetal calf serum
      (FCS)/PBS suspensions. Cell viability subsequent to exposure was evaluated after
      0 h, 6 h and 18 h using the methylthiazoletetrazolium (MTT) assay and compared to
      pretreatment values. At a TriP[4] concentration previously demonstrated to induce
      a 5 log(10)-unit reduction in a viable count for S. aureus, 79% of the
      fibroblasts were photo-inactivated. Increasing the FCS concentration in the
      medium protected the fibroblasts against PDI. Based on our in vitro results, we
      propose that in vivo PDI of S. aureus holds potential; however, PDI of P.
      aeruginosa and C. albicans will probably require such a strong PDI regime that it
      will induce substantial damage to fibroblasts.

PMID- 15940571
TI  - [The freiburg incision for cochlear implantation -- initial results].
AB  - BACKGROUND: Cochlear implant surgery is a well standardized therapy for
      rehabilitation of congenital or acquired deafness at all ages. Mastoidectomy,
      posterior tympanotomy, cochleostomy and electrode insertion are performed
      consistently worldwide. Recently newly developed types of incision are taken into
      account. In our experience over more than 15 years the extended endaural incision
      has proven to be reliable with a low complication rate. OBJECTIVE: To evaluate a
      modified retroauricular incision for clinical use and complication rate in
      cochlear implant surgery with devices of different manufacturers. MATERIAL AND
      METHODS: We performed a prospective analysis of cochlear implant surgeries
      between 03/2003 and 03/2004. In all cases a modified retroauricular incision was
      used. Necessary adaptations of incision, depending on the device used, and
      postoperative complications were evaluated. RESULTS: In 76 ears a retroauricular
      incision was performed. Depending on the shape and size of receiver/stimulator an
      extension of the incision was necessary. The mean observation time was 6.3
      months. Intra- or postoperative complications were not observed. In one case a
      skin dehiscence following trauma 28 days after surgery was reported without
      dehiscence of fascia or implant failure with uneventful healing after secondary
      suture. CONCLUSIONS: With regard to the results with the extended endaural
      incision the modified retroauricular incision allows a safe access for cochlear
      implant surgery. Observation of long term results and outcomes in revision
      surgery is mandatory.

PMID- 15940572
TI  - [Towards a cellular pathophysiology of Meniere's disease].
AB  - BACKGROUND: A modest increase in the hydrostatic pressure within the
      endolymphatic space may induce an endolymphatic hydrops which in turn is
      typically associated with Meniere's disease. However, there is no convincing
      pathophysiological model that might explain, on a cellular level, how a pressure
      increases may cause disturbed functions of vestibular hair cells and vertigo
      attacks. METHODS: So far, models involve osmotic mechanisms leading to
      electrolyte imbalances in the endolymphatic space. Alternatively, impaired
      longitudinal flow in the endolymphatic space is considered important. RESULTS:
      Recently, a pressure-sensitive potassium current was identified and characterized
      in vestibular hair cells. CONCLUSIONS: This current may modify the frequency
      behavior of a cell and may be the "missing link" in a cellular pathophysiology of
      the hydrops. Ion currents in hair cells offer attractive targets for
      pharmacological interventions in Meniere's disease.

PMID- 15940573
TI  - [LED autoregistration in navigated endonasal sinus surgery].
AB  - BACKGROUND: In endonasal sinus surgery, computer aided surgery (CAS) is a
      generally accepted method. Applying CAS, there are basic problems with the
      constancy of accuracy at a free mobile patient head as well as with extended
      referencing time. The navigation system manufacturer Stryker-Leibinger invented
      together with our working group a non-invasive, frameless, automatic patient
      registration and simultaneous tracking system for navigated endonasal sinus
      surgery. With this new user-friendly system it concerns an active, LED-based,
      self-adhesive on the surface of splanchnocranium autoregistration mask. MATERIAL
      AND METHOD: The LED autoregistration mask was tested in an anatomic cadaver study
      and an ongoing clinical patient study regarding manageability, applicability and
      accuracy. Accuracy measurements were accomplished on different control points of
      the head in the cadaver study. The determination of accuracy was calculated with
      the metric Euclidean distance. Further we report on our experiences with a total
      of 20 patients applying the new mask. To control the accuracy, anatomic landmarks
      of the patients were adducted. Goal of our study was to determine the accuracy of
      the LED mask and to compare it with titanium screw markers, the valid reference
      gold standard. RESULTS: The LED autoregistration mask convinced by a high
      precision with relatively simple useability. Total accuracy amounted to 2.22 +/-
      0.91 mm. The LED system proved to be a valuable orientation guide mainly at
      revision surgeries with modified anatomy. CONCLUSIONS: LED surface
      autoregistration is especially suitable for endonasal sinus surgery and
      represents a very helpful tool for the rhinosurgeon. Our accuracy studies have
      shown that the LED autoregistration mask is comparable to the gold standard
      titanium screw markers and, in addition, very reliable.

PMID- 15940574
TI  - [A historic case of Wegener's granulomatosis: the physicist who discovered the
      electromagnetic waves: Heinrich Hertz].
AB  - SUMMARY: A diary and an extensive correspondence of Heinrich Hertz and his family
      provide a meticulous documentation of his life, made available by Albrecht
      Folsing in 1997 through a carefully investigated biography, which permit the
      conclusion that H. Hertz died of Wegener's granulomatosis, 45 years before this
      disease had been explored. WEGENER'S GRANULOMATOSIS: The symptoms of the
      granulomatosis, that was first described by Friedrich Wegener in 1936 and 1939
      are presented in short with literal quotations of the author: It begins with a
      refractory cold that will last until the end, then follow involvement of the
      paranasal sinuses, ears, mucous lining of mouth and pharynx, slight fever,
      weakness, in the final phase dissemination with nephritis, septic fever,
      arthritis, myalgia, paralyses leading to total immobility, exitus. The etiology
      is not fully understood but probably based on immunoreaction. H. HERTZ:
      CURRICULUM VITAE: Born in Hamburg, Germany, in 1857: after secondary school
      academic training in physics at Dresden, Munic and Berlin. 1885 professor of
      physics in Karlsruhe, then starting in 1889 at Bonn. 1887/88 exploration of the
      electromagnetic waves, now the basis for all radio communication, and exploration
      of the photoelectric effect, the basis of solar techniques. Numerous highranking
      distinctions. H. HERTZ: THE CASE HISTORY: The case history is presented in detail
      based on numerous literal quotations from personal letters and the diary. After a
      few banal affections involving the teeth and toes the systemic disease became
      manifest in summer 1892 with a refractory cold which remained the focus of
      treatment until death. Granulation tissue in the nose that was excised several
      times: no tuberculosis, no carcinoma. Otitis with purulent mastoiditis, in
      October 1892 mastoidectomy, persistent purulence. Early in 1893 diagnosis of
      nephritis. Extraction of a superior tooth, punturing of the maxillary sinus, then
      twice radical opening of the maxillary sinus. Painful ankylosis and paralyses
      ending in complete immobility, hyperthermy, exitus on Jan. 1 1894. DISCUSSION:
      The case history is repeated in short and discussed. At that time a diagnosis and
      an effective therapy were not available. Today the disease could have been kept
      under control applying immunosuppressive and antibiotic treatment.

PMID- 15940575
TI  - [Report of a spindle cell myoepithelialioma of the minor salivary glands with
      extensive lipomatous component].
AB  - Myoepitheliomas of the salivary glands are rare benign tumors composed of spindle
      shaped myoepithelial cells, but may show plasmacytoid, epitheloid and clear cell
      types that principally exhibit myoepithelial but not ductal differentiation.
      These tumors are mainly located in the major salivary glands and have sometimes
      abundant, acellular, mucoid or hyaline stroma but lack chondroid and
      myxochondroid foci, probably representing the one end of the spectrum of
      pleomorphic adenoma. Lipomatosis in the form of isolated small islands or
      scattered single lipocytes, is quite uncommon, and a large amount of adipose
      tissue in a pleomorphic adenoma and myoepithelioma is a rarity and only described
      in major salivary glands. We present the case report of a 38-year old man with a
      myoepithelioma of the minor palatinal salivary glands with extensive lipomatosis
      as an example of this rare phenomena.

PMID- 15940576
TI  - [Principles of hearing aids].
AB  - The diagnostic and therapy of hearing impairment is one of the main tasks of the
      Otolaryngologist. This article deals with the treatment of hearing aids in adults
      and young persons according to the laws and the guidelines of the "Heil- und
      Hilfsmittelrichtlinien" in Germany. It shall serve the Otolaryngologist as a
      guideline. The second part of the article is about the different strategies to
      adjust hearing aids. Then the examination of the hearing aids by the
      otolaryngologist is described. Finally the importance of aftercare is stressed
      and the future of hearing aids in Germany according to the concept of "OHRWELL"
      is pointed out.

PMID- 15940579
TI  - Shift happens: using outcomes to survive and thrive under PPS.
AB  - In the post prospective payment system (PPS) era, acute rehabilitation providers
      are presented with multiple challenges and opportunities. All inpatient
      rehabilitation facilities (IRFs) face the requisite demands for improved
      efficiency (e.g., reduced length of stay for persons with stroke) and the re
      institution of monitoring for compliance with the 75% rule. However IRFs also now
      have a dramatic opportunity to shift the paradigm of "how we do business" by
      adopting cutting edge technology and continuous quality improvement methodology
      and by rethinking and revising how we evaluate a stroke program. Today, more than
      ever before in our industry, providers have an opportunity to evolve to a
      consumer-driven program evaluation model with the resultant modification of
      rehabilitation outcomes, indicators, and metrics. The article argues for a
      climactic and dramatic change in how acute rehabilitation providers market for
      patients, deliver care, and report on their outcomes. In the current context of
      PPS and the 75% rule, we are quite literally considering the survival of the
      industry as we know it. Improved rehabilitation processes and revised
      rehabilitation report cards (customized for the various stakeholders) hold the
      key to market share and organizational success. If patient access, quality
      outcomes, patient safety, and functional gains are to be achieved, the industry
      needs to change the way it does business and as a consequence the way it
      evaluates its programs.

PMID- 15940580
TI  - Medicare reform and the American devolution.
AB  - The Medicare Modernization Act of 2003 (MMA'03) did more than introduce a
      prescription drug benefit for Medicare beneficiaries; it also laid the groundwork
      for several far-reaching changes in the Medicare program. These changes must be
      considered in the context of the "American devolution"--a much larger shift in
      American health and social policy that is changing how Americans manage their
      health and wealth as more tasks and responsibilities devolve to individuals in
      managing their personal affairs and their lives in the workplace. The devolution
      presents a special challenge to those who have diminished capacities for self
      direction, including many stroke survivors who are especially dependent on the
      Medicare program for their rehabilitation and management of their diminished
      health status. This article calls for a massive investment in information
      technology and brokerage that will enable all Americans to effectively navigate
      the brave new world that the changes in the Medicare program portend.

PMID- 15940581
TI  - Functional neuroimaging in motor recovery after stroke.
AB  - Neuroimaging techniques provide information on the neural substrates underlying
      functional recovery after stroke, the number one cause of long-term disability.
      Despite the methodological difficulties, they promise to offer insight into the
      mechanisms by which therapeutic interventions can modulate human cortical
      plasticity. This information should lead to the development of new, targeted
      interventions to maximize recovery.

PMID- 15940582
TI  - Advances in the understanding and treatment of stroke impairment using robotic
      devices.
AB  - The presence of robotic devices in rehabilitation centers is now becoming
      commonplace across the world, challenging heath care professionals to rethink
      treatment strategies for motor impairment in hemiparetic stroke patients. In this
      article, we will discuss some of the motivations for using these devices, review
      clinical outcomes following robotic-assisted training in both the upper and lower
      extremities, and detail how these devices can provide quantitative evaluations of
      function. We will also address the clinical issues that need to be considered
      when using robotic devices to treat stroke patients, and finally a vision of
      where this field is heading will be discussed.

PMID- 15940583
TI  - Opening the black box of stroke rehabilitation with clinical practice improvement
      methodology.
AB  - Although stroke survivors are the largest consumer group for postacute
      rehabilitation services, there has been little quantification of the details of
      poststroke rehabilitation (PSR), with the major exception of the AHCPR Clinical
      Practice Guidelines #16 of 1995. The gold standard research methodology of a
      randomized controlled trial cannot practically encompass PSR. Using clinical
      practice improvement (CPI), a statistically based, validated research
      methodology, a mathematical representation of the inpatient stroke rehabilitation
      experience has been constructed. This article examines the principle aspects of
      CPI methodology and how it was adapted to a multicenter study of inpatient PSR.

PMID- 15940584
TI  - Management of communication disorders using family member input, group treatment,
      and telerehabilitation.
AB  - Today, speech-language pathologists (SLPs) practice stroke rehabilitation in
      environments where they have less time to manage the communication impairments of
      patients who are more medically fragile than ever before. Many SLPs have
      creatively adapted their practice to maximize functional outcomes for their
      patients. This article highlights three techniques designed to enhance functional
      SLP outcomes: maximizing family member input; providing group treatment; and
      providing treatment in remote, functional settings via telepractice technology.

PMID- 15940585
TI  - A new approach to patient-centered care.
AB  - An opportunity existed at our rehabilitation hospital, in preparation for
      Medicare's Prospective Payment System (PPS) in acute medical rehabilitation, to
      develop an integrated inpatient care model using all available resources. The
      results have been an improved practice of all staff, increased efficiency and
      productivity, and increased staff and patient satisfaction. This article
      discusses the drivers for changing the team model within a large rehabilitation
      hospital. It includes an overview of the process of data gathering prior to
      changing the team model, how the new team model functions, and follow-up data
      collection 9 months after to provide evidence on what changes worked and what
      areas required further change to meet the objectives.

PMID- 15940586
TI  - The relationship between functional independence scores on admission and patient
      falls after stroke.
AB  - This study explores the relationships between patient admission scores on the FIM
      tool for patients admitted with stroke and their risk for falling within the
      first 5 days of admission to an acute rehabilitation hospital.

PMID- 15940587
TI  - Stroke knowledge and misconceptions among survivors of stroke and a non-stroke
      survivor sample.
AB  - PURPOSE: To investigate stroke knowledge, knowledge gaps, and misconceptions
      about stroke among stroke survivors and non-stroke survivors. METHOD: Archival
      data from a stroke knowledge test administered to 38 non-stroke survivors
      (community sample) were compared to data collected for this study from 42 stroke
      survivors. RESULTS: No difference in the overall level of stroke knowledge
      between groups was found. There were 12 issues about which stroke survivors and
      non-stroke survivors appear to have good understanding (e.g., the role of aspirin
      in preventing stroke). There were a smaller number of issues about which
      participants from both groups reported they lacked knowledge (e.g., the
      relationship between TIAs and stroke) or held erroneous beliefs (e.g., the effect
      of atrial fibrillation on stroke risk). CONCLUSION: There is a continuing need
      for education about stroke. Particular areas on which such programs might need to
      focus are identified.

PMID- 15940588
TI  - Family presence at cardiopulmonary resuscitation: considerations in a
      rehabilitation hospital.
AB  - The presence of family members in the resuscitation room is an issue that is
      extremely controversial, with strong opinions for and against the practice in
      both medical and lay communities. Routinely, family members have remained in a
      nearby waiting room while resuscitative efforts were performed on a loved one.
      Meanwhile, medical and nursing personnel, driven by their desire to meet the
      needs of the patient, may not have considered the needs of the family. Recently,
      a movement has begun that has challenged and provoked a change in practice in
      institutions across the United States and beyond. Research shows that a vast
      majority of family members wish to be present or, at minimum, be given the
      opportunity to be present. Health care providers have mixed opinions, with more
      nurses in favor than physicians. Patients expressed appreciation for the presence
      of and support by a family member during the emergency. Family presence is a
      difficult issue; presently there is no universally satisfactory conclusion. The
      purpose of this article is to explore the movement of family presence at
      resuscitation and its adoption in rehabilitation hospitals.

PMID- 15940595
TI  - Operation Iraqi Freedom: the Landstuhl Regional Medical Center experience.
AB  - Landstuhl Regional Medical Center, Germany, the only American medical center in
      Europe, received approximately 80% of American military patients evacuated out of
      theater during the first 4 months of Operation Iraqi Freedom. 1236 patients
      arrived at Landstuhl Regional Medical Center from the beginning of Operation
      Iraqi Freedom until May 15, 2003, consisting of 256 battle casualties (20.7%),
      510 injury patients (41.3%), and 470 disease patients (38.0%). Retrospective
      record reviews were done on all battle casualties, as well as all disease and
      injury patients with a musculoskeletal diagnosis. Of the battle casualty
      patients, 68.4% suffered an extremity injury--a percentage that is consistent
      with that from prior wars. 52.8% had a lower extremity injury and 21.5% had a
      foot or ankle injury. Additionally, of all disease and non-battle injury patients
      with a musculoskeletal diagnosis, 74.7% had an extremity complaint, 44.1% had a
      lower extremity diagnosis, and 23.2% had foot or ankle pathology. Of all 1236
      patients evacuated during this period, 39.5% had extremity pathology, 25.8% had
      lower extremity pathology, and 12.4% had foot and ankle pathology in isolation or
      combined with other complaints. Extremity injuries, and specifically lower
      extremity injuries, continue to be the predominant wounding pattern found in
      surviving troops in modern warfare. Proper staffing and positioning of medical
      specialties involved in musculoskeletal trauma care is vital in ensuring proper
      casualty care in future conflicts.

PMID- 15940596
TI  - The value of radiographic parameters in the surgical treatment of hallux rigidus.
AB  - The purpose of this study was to determine if metatarsal protrusion or the length
      of the first and second rays were associated with the incidence of hallux
      rigidus. For this retrospective study, anteroposterior radiographs from 51
      patients diagnosed with hallux rigidus and 51 patients without evidence of hallux
      rigidus were selected for review as a control group. Radiographs were randomly
      assigned to one of two raters who determined the metatarsal protrusion distance,
      first metatarsal length, second metatarsal length, length of the proximal phalanx
      of the hallux, length of the proximal phalanx of the second toe, and overall
      hallux length. A statistical comparison of these radiographic measurements showed
      only first metatarsal length to significantly differ (P = .05) between the two
      groups (65.4 +/- 5.3 mm and 67.7 +/- 5.9 mm for the hallux rigidus and control
      groups, respectively). The findings of this study suggest the need to revisit the
      role that metatarsal protrusion distance and first metatarsal length play in the
      etiology of hallux rigidus. In addition the need to surgically correct a long
      first metatarsal should be further evaluated.

PMID- 15940597
TI  - Radiographic investigation of angular and linear measurements including first
      metatarsophalangeal joint dorsiflexion and rearfoot to forefoot axis angle.
AB  - This study investigated intra- and inter-rater reliability of several
      radiographic angular and linear parameters using 6 subjects. Using standard
      weight-bearing radiographs, the following measurements were performed: first
      metatarsal protrusion distance, hallux abductus, first intermetatarsal, calcaneal
      inclination and lateral intermetatarsal angles. Measurement of lateral stressed
      dorsiflexion of the first metatarsophalangeal joint and the rearfoot-to-forefoot
      axis angle taken using a composite view were also obtained. All parameters were
      measured independently by 2 raters, and measurements were repeated on 3 separate
      occasions at weekly intervals. Intrarater reliability of radiographic
      measurements ranged between R = 0.65-1.00 for lateral stressed dorsiflexion, and
      between R = 0.91 and 0.99 for the rearfoot to forefoot axis angle. Inter-rater
      reliability of radiographic measurements ranged from R = 0.82-0.99. Specifically,
      lateral stressed dorsiflexion showed R = 0.87 with a mean difference of -1.47
      (confidence interval [CI]: -3.42, 0.47), indicating no significant difference ( t
      = 1.54, P = 0.13). The rearfoot-to-forefoot-axis angle showed R = 0.92 with a
      mean difference of -0.15 (CI: -1.05, 0.74), indicating no significant difference
      ( t = 0.35, P = 0.73). The 7 angular and linear measurements chosen demonstrated
      high inter- and intrarater reliability. These results indicate that weight
      bearing radiographic first metatarsophalangeal joint dorsiflexion using the
      lateral stressed dorsiflexion view, and measurement of the rearfoot-to-forefoot
      axis angle using a composite view could be measured reliably within and between
      raters.

PMID- 15940598
TI  - The incidence of the intermetatarsal facet of the first metatarsal and its
      relationship to metatarsus primus varus: a cadaveric study.
AB  - The purpose of this study was to determine the incidence of the intermetatarsal
      facet on the lateral aspect of the base of the first metatarsal and its role in
      the medial angulation of the proximal metatarsal base as it relates to metatarsus
      primus varus. A total of 77 human first metatarsals were examined for the
      presence of the intermetatarsal facet. The intermetatarsal facet was seen on the
      lateral aspect of the first metatarsal base, superior to the tuberous attachment
      of the peroneus longus tendon. The obliquity of the first metatarsal base was
      measured on metatarsals with and without the intermetatarsal facet. The
      intermetatarsal facet was present on 22 of 77 first metatarsals, or 29% of
      specimens. The proximal obliquity angle was 2.92 degrees in metatarsals without
      the facet and 4.63 degrees when the facet was present. This increase in the
      medial obliquity of the proximal first metatarsal base in the presence of an
      intermetatarsal facet was statistically significant (P < .002). The
      intermetatarsal facet between the first and second metatarsals may have a role in
      an increased medial obliquity of the first metatarsal base and is present in
      approximately 30% of the population.

PMID- 15940599
TI  - Fixation of the chevron osteotomy with an absorbable copolymer pin for treatment
      of hallux valgus deformity.
AB  - This study investigated the use of a bioabsorbable pin made of an oriented poly-L
      lactic acid/polyglycolic acid (82:18 ratio) copolymer to fix distal chevron
      osteotomies in 15 patients (18 feet), with an average follow-up of 18 months.
      This material absorbs faster than poly-L-lactic acid and slower than poly-p
      dioxanone, 2 bioabsorbable polymers that have a clinical history in fixation of
      distal chevron osteotomies. The average intermetatarsal angle significantly
      decreased from 11.9+/-1.7 degrees to 0.9+/-3.8 degrees (P < .001) while the
      average hallux valgus angle significantly decreased from 19.4+/-4.7 degrees to
      6.2+/-6.4 degrees (P < .001). The preoperative American Orthopaedic Foot and
      Ankle Society's hallux-metatarsophalangeal-interphalangeal score averaged 44.6+/
      15.1, which increased significantly to 87.4+/-14.9 (P < .001) postoperatively. In
      1 procedure, a giant cell granuloma developed that was treated with debridement.
      Overall, these results were comparable to those derived from the use of other
      methods of fixation used for bunionectomies.

PMID- 15940600
TI  - Long-term results of ankle fractures with a posterior malleolar fragment.
AB  - The aim of this study was to evaluate 1) long-term results of ankle fractures
      with a posterior malleolar fragment, and 2) the need for fixation of fragments
      smaller than 25%. Forty-five patients with ankle fractures and a posterior
      malleolar fragment were evaluated. Mean follow-up was 13 years (range, 2-24). The
      size and fixation of the fragment were registered. Outcome was assessed using an
      Ankle Fracture Scoring System (maximum: 150 points), a 10-point Numeric Scale for
      Pain (1 = no pain, 10 = unbearable pain) and an OsteoArthritis Score (0 = no
      osteoarthritis, 3 = severe osteoarthritis). The mean Ankle Fracture Scoring
      System, Numeric Scale for Pain and Osteoarthritis-score were 124, 2.5, and 1.2,
      respectively. The mean size of fixated fragments was significantly larger than
      that of nonfixated fragments (30% versus 16%). Those patients in which the
      posterior malleolar fragment was fixated did not have a statistically significant
      better outcome than those patients in which the fragments were not fixated (Ankle
      Fracture Scoring System: 119 versus 126, Numeric Scale for Pain: 2.6 versus 2.4,
      Osteoarthritis-score: 1.0 versus 1.2). There was no significant correlation
      between outcome and size of unfixated fragments. Fracture-dislocation was seen
      more often in combination with larger fragments (24% versus 15%) and resulted in
      statistically significant worse long-term outcome than nondislocated fractures,
      except for pain (Ankle Fracture Scoring System: 115 versus 134, Osteoarthritis
      score: 1.7 versus 0.8). In conclusion, patients showed good results after 13
      years follow-up and there was no evidence for the need for fixation of fragments
      smaller than 25%.

PMID- 15940601
TI  - Freiberg's infraction in identical twins: a case report.
AB  - Freiberg's infraction is an ostechondrosis of a lesser metatarsal head resulting
      in degeneration of the metatarsophalangeal joint. Several mechanisms have been
      suggested in its pathenogenesis. Freiberg first described the entity and believed
      single impact trauma was the underlying cause. Repetitive biomechanical
      microtrauma is the most widely accepted etiologic theory. Other factors
      contributing to its development include aseptic necrosis, ischemia, and a
      congenital predisposition. We present a case report of Freiberg's infraction
      occurring in identical twins involving multiple metatarsals in various stages of
      degeneration. One of the twins was affected unilaterally whereas the other twin
      was affected bilaterally. Both twins had involvement of the second metatarsal on
      the same side extremity. The occurrence of Freiberg's infraction in identical
      twins suggests that an underlying congenital predisposition to the condition may
      play more of a role than previously considered.

PMID- 15940602
TI  - Longitudinal tears of both peroneal tendons associated with tophaceous gouty
      infiltration. A case report.
AB  - The authors report a case of longitudinal tendon tears of the peroneus longus and
      brevis in the presence of tophaceous gouty infiltration. There are a limited
      number of reports discussing similar processes affecting various tendons
      throughout the body. There has been 1 prior case of peroneal tendon involvement
      affecting only the peroneus brevis. A 35-year-old man presented with a 4-year
      history of left-sided lateral ankle pain, redness, and swelling. The patient
      described the "attacks" as occurring off and on, with a recent increase in
      frequency. The symptoms were relieved with indomethacin, colchicine, and narcotic
      analgesics. Upon clinical evaluation, there was a cavus foot type with moderate
      calcaneal varus. Peroneal subluxation was elicited with resisted eversion. An MRI
      evaluation revealed longitudinal tears of both peroneal tendons. During surgical
      repair, a chalky-white substance resembling gouty tophi was present within both
      tendon tears. The tendons were remodeled and repaired. The patient had an
      uneventful postoperative course with nearly completed resolution of his symptoms
      at 1-year follow-up. The patient was referred to his primary care physician for
      further evaluation and long-term control of elevated uric acid levels.

PMID- 15940603
TI  - Persistent diastasis in a Maisonneuve fracture--interposition of a tibial
      osteochondral fragment: a case report.
AB  - We report a case of failed reduction of the distal tibiofibular syndesmosis
      following a Maisonneuve fracture due to interposition of an osteochondral
      fragment in the syndesmosis from the tibial plafond. The displaced fragment was
      not initially appreciated. It is suggested that surgeons consider this as a
      possible cause of an incompletely reduced diastasis after deltoid ligament
      interposition has been excluded.

PMID- 15940604
TI  - Naviculocuneiform dislocations treated with immediate arthrodesis: a report of 2
      cases.
AB  - The authors report on 2 patients who sustained naviculocuneiform dislocations and
      intercuneiform diastasis, and who were treated with immediate arthrodesis of the
      midfoot complex. Injury patterns in both cases involved damage to the medial
      facet of the distal navicular articular surface, separation of the first and
      second cuneiforms, and an unstable first ray. At the 15- and 18-month follow-up,
      respectively, both patients attained a stable, solid fusion with maintenance of
      the medial longitudinal architecture. Both patients returned to their preinjury
      activity levels with no disability.

PMID- 15940605
TI  - Tailor's bunion: a review.
AB  - The tailor's bunion is a painful bony prominence on the lateral aspect of the
      fifth metatarsal head that occurs in many individuals, but seldom causes
      symptoms. This article reviews the current literature regarding the presentation,
      etiology, and management of the tailor's bunion. The first line of management
      should be conservative, with advice on shoe wear. Orthotics may be useful if a
      symptomatic tailor's bunion results from excessive subtalar joint pronation.
      Operative management, indicated when symptoms are not controlled nonoperatively,
      aims to decrease foot width and the prominence of the tailor's bunion. Procedures
      can be grouped into resections and distal, diaphyseal, and proximal osteotomies.
      A distal osteotomy is recommended if medial translation of the head for one-third
      of the width of the metatarsal shaft produces a normal fourth-fifth
      intermetatarsal angle. A proximal osteotomy can be performed in the face of
      larger deformities. The management of recurrent tailor's bunion is still
      controversial. If the recurrence is due to under-correction, or if the initial
      procedure was not the best suited to that particular patient, then revision
      surgery may be helpful, after the cause of the failure has been established.
      Although unpopular, resection should be considered as the final salvage
      procedure.

PMID- 15940606
TI  - The brevis buttress effect in hallux valgus surgery.

PMID- 15940607
TI  - Lesser digital fusion with a cannulated screw.

PMID- 15940608
TI  - Valdecoxib withdrawal leaves pain relief treatment gap.

PMID- 15940609
TI  - Functional GI disorders: what's in a name?

PMID- 15940610
TI  - Image of the month. Gastric signet-ring-cell carcinoma with leptomeningeal
      carcinomatosis.

PMID- 15940611
TI  - Differentiation of in vitro-modified human peripheral blood monocytes into
      hepatocyte-like and pancreatic islet-like cells.
AB  - BACKGROUND & AIMS: Adult stem cells provide a promising alternative for the
      treatment of diabetes mellitus and end-stage liver diseases. We evaluated the
      differentiation potential of human peripheral blood monocytes into hepatocyte
      like and pancreatic islet-like cells. METHODS: Monocytes were treated with
      macrophage colony-stimulating factor and interleukin 3 for 6 days, followed by
      incubation with hepatocyte and pancreatic islet-specific differentiation media.
      Cells were characterized by flow cytometry, gene-expression analysis, metabolic
      assays, and transplantation for their state of differentiation and tissue
      specific functions. RESULTS: In response to macrophage colony-stimulating factor
      and interleukin 3, monocytes resumed cell division in a CD115-dependent fashion,
      which was associated with a down-regulation of the PRDM1 and ICSBP genes. These
      programmable cells of monocytic origin were capable of differentiating into
      neohepatocytes, which closely resemble primary human hepatocytes with respect to
      morphology, expression of hepatocyte markers, and specific metabolic functions.
      After transplantation into the liver of severe combined immunodeficiency
      disease/nonobese diabetic mice, neohepatocytes integrated well into the liver
      tissue and showed a morphology and albumin expression similar to that of primary
      human hepatocytes transplanted under identical conditions. Programmable cells of
      monocytic origin-derived pancreatic neoislets expressed beta cell-specific
      transcription factors, secreted insulin and C peptide in a glucose-dependent
      manner, and normalized blood glucose levels when xenotransplanted into
      immunocompetent, streptozotocin-treated diabetic mice. Programmable cells of
      monocytic origin retained monocytic characteristics, notably CD14 expression, a
      monocyte-specific methylation pattern of the CD115 gene, and expression of the
      transcription factor PU.1. CONCLUSIONS: The ability to reprogram, expand, and
      differentiate peripheral blood monocytes in large quantities opens the real
      possibility of the clinical application of programmable cells of monocytic origin
      in tissue repair and organ regeneration.

PMID- 15940613
TI  - Positron emission tomography imaging of adenoviral-mediated transgene expression
      in liver cancer patients.
AB  - BACKGROUND & AIMS: In gene-therapy protocols, imaging of gene expression is
      needed to evaluate the transduction efficiency of the vector, its tissue
      distribution, and the duration of transgene expression and to assess the
      feasibility of repeated vector administration. METHODS: We have used positron
      emission tomography with a fluorine-18-labeled penciclovir analogue to monitor
      thymidine kinase gene expression after intratumoral injection of a first
      generation recombinant adenovirus in patients with hepatocellular carcinoma.
      Patients were enrolled in a pilot clinical trial and treated with escalating
      doses of the vector. Two days after adenovirus inoculation, transgene expression
      was evaluated during the first hours after administration of the radiotracer both
      on the treated lesion and on a whole-body basis. RESULTS: Transgene expression in
      the tumor was dependent on the injected dose of the adenovirus and was detectable
      in all patients who received > or = 10(12) viral particles. However, when the
      study was repeated 9 days after vector injection, no expression could be
      observed. It is interesting to note that no specific expression of the transgene
      could be detected in distant organs or in the surrounding cirrhotic tissue in any
      of the cases studied. CONCLUSIONS: Our findings show the real possibility of
      imaging transgene expression in humans by using viral vectors. We show that
      hepatocarcinoma is a permissive tumor for adenoviral infection and that the
      nontumoral cirrhotic liver is spared from transduction when the vector is
      administered by intratumoral injection. These results show that positron emission
      tomography imaging may help in the design of gene-therapy strategies and in the
      clinical assessment of new-generation vectors.

PMID- 15940614
TI  - Human colorectal cancer cells induce T-cell death through release of proapoptotic
      microvesicles: role in immune escape.
AB  - BACKGROUND & AIMS: Normal and neoplastic cells release microvesicles, whose
      effects on the immune system still need to be elucidated. Because human
      colorectal cancer cells are hypothesized to escape immune recognition by
      expressing proapoptotic molecules, we investigated whether microvesicles bearing
      Fas ligand and tumor necrosis factor-related apoptosis-inducing ligand and
      inducing apoptosis of activated T cells are secreted by colorectal cancer cells
      both in vitro and in affected patients. METHODS: Fas ligand and tumor necrosis
      factor-related apoptosis-inducing ligand expression were analyzed in colorectal
      cancer cells and purified microvesicles by flow cytometry, Western blotting, and
      immunoelectron microscopy. Microvesicle tumor origin was assessed through
      simultaneous detection of lysosomal (CD63) and adenocarcinoma (carcinoembryonic
      antigen) markers. Proapoptotic activity of microvesicles was evaluated by annexin
      V/propidium iodide staining and caspase activation in T cells, including CD8+ T
      lymphocytes from colorectal cancer patients. RESULTS: Colorectal cancer cells
      showed a granular pattern of tumor necrosis factor-related apoptosis-inducing
      ligand and Fas ligand expression, suggesting a secretory behavior. These
      proapoptotic molecules were detected on isolated microvesicles, together with
      class I HLA, CD63, and carcinoembryonic antigen. Microvesicles induced Fas ligand
      mediated and tumor necrosis factor-related apoptosis-inducing ligand-mediated
      apoptosis of activated CD8+ T cells generated from colorectal cancer patients.
      Microvesicles with comparable phenotypes and functions were found in plasma from
      patients with advanced disease, whereas vesicular structures expressing Fas
      ligand and tumor necrosis factor-related apoptosis-inducing ligand were also
      detected in colorectal cancer specimens. CONCLUSIONS: These data show that
      colorectal cancer induces T-cell apoptosis through the release of Fas ligand
      bearing and tumor necrosis factor-related apoptosis-inducing ligand-bearing
      microvesicles both in vitro and in vivo. This mechanism of immune escape has
      potential implications as a prognostic factor and could be targeted for the
      development of new antitumor therapies in colorectal cancer patients.

PMID- 15940615
TI  - Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a
      randomized, placebo-controlled study.
AB  - BACKGROUND & AIMS: Despite treatment with corticosteroids, severe to moderately
      severe attacks of ulcerative colitis have a high colectomy rate. We intended to
      find a rescue therapy other than cyclosporin A, which imposes a high risk of side
      effects and cyclosporine-related mortality. METHODS: This was a randomized double
      blind trial of infliximab or placebo in severe to moderately severe ulcerative
      colitis not responding to conventional treatment. Patients were randomized to
      infliximab/placebo either on day 4 after the initiation of corticosteroid
      treatment if they fulfilled the index criteria for fulminant ulcerative colitis
      on day 3 or on day 6-8 if they fulfilled index criteria on day 5-7 for a severe
      or moderately severe acute attack of ulcerative colitis. Results were analyzed
      according to the intention-to-treat principle. The primary end point was
      colectomy or death 3 months after randomization. Secondary end points were
      clinical and endoscopic remission at that time in patients who did not undergo
      operation. RESULTS: Forty-five patients were included (24 infliximab and 21
      placebo). No patient died. Seven patients in the infliximab group and 14 in the
      placebo group had a colectomy (P = .017; odds ratio, 4.9; 95% confidence
      interval, 1.4-17) within 3 months after randomization. No serious side effects
      occurred. Three patients in the placebo group required operation for septic
      complications. CONCLUSIONS: Infliximab 4-5 mg/kg is an effective and safe rescue
      therapy in patients experiencing an acute severe or moderately severe attack of
      ulcerative colitis not responding to conventional treatment.

PMID- 15940616
TI  - A randomized, double-blind, controlled withdrawal trial in Crohn's disease
      patients in long-term remission on azathioprine.
AB  - BACKGROUND & AIMS: An open study reported that patients with Crohn's disease in
      remission who have taken azathioprine for longer than 3.5 years are at low risk
      of relapse when azathioprine is discontinued. To confirm this observation, we
      performed a multicenter, double-blind, noninferiority withdrawal study. METHODS:
      Patients who were in clinical remission on azathioprine for > or = 42 months were
      randomized to continue azathioprine or to receive an equivalent placebo for 18
      months. The primary end point was clinical relapse at 18 months. RESULTS: Forty
      patients were randomly assigned to receive azathioprine and 43 to receive
      placebo. Characteristics of patients at entry were similar in the 2 study groups.
      At 18 months, 3 patients had a relapse in the azathioprine group, and 9 had a
      relapse in the placebo group. Kaplan-Meier estimates of the relapse rate at 18
      months were 8% +/- 4% and 21% +/- 6%, respectively. The hypothesis that placebo
      was inferior to azathioprine was not rejected (P = .195). Among the baseline
      variables, C-reactive protein level > 20 mg/L, time without steroids < 50 months,
      and hemoglobin level < 12 g/dL were found to be predictive of relapse in the
      multivariate analysis. CONCLUSIONS: This study shows that azathioprine withdrawal
      is not equivalent to continued therapy with azathioprine for maintenance of
      remission in patients with Crohn's disease who have been in remission on
      azathioprine for > or = 3.5 years. Thus, azathioprine maintenance therapy should
      be continued beyond 3.5 years.

PMID- 15940617
TI  - Brain response to visceral aversive conditioning: a functional magnetic resonance
      imaging study.
AB  - BACKGROUND & AIMS: Brain-imaging studies to date have confounded visceral pain
      perception with anticipation. We used functional magnetic resonance imaging of
      the human brain to study the neuroanatomic network involved in aversive
      conditioning of visceral pain and, thus, anticipation. METHODS: Eight healthy
      volunteers (5 male) participated in the study. We used a classic conditioning
      paradigm in which 3 neutral stimuli (differently colored circles) that acted as
      conditioned stimuli were paired with painful esophageal distention, air puff to
      the wrist, or nothing, which acted as unconditioned stimuli. Neural activity was
      measured during learning, anticipation (pairing only 50% of conditioned stimuli
      with their unconditioned stimuli), and extinction (unpaired conditioned stimuli)
      phases. For magnetic resonance imaging, axial slices depicting blood oxygen level
      dependent contrast were acquired with a 1.5-T system. RESULTS: Neural responses
      during the learning phase included areas commonly associated with visceral pain
      (anterior cingulate cortex, insula, and primary and secondary somatosensory
      cortices) and innocuous somatosensory perception (primary and secondary
      somatosensory cortices and insula). During the anticipation and extinction phases
      of aversive stimulation, brain activity resembled that seen during actual painful
      esophageal stimulation. In contrast, anticipation and extinction of the innocuous
      somatic stimulus failed to show that effect. CONCLUSIONS: We have shown that
      actual and anticipated visceral pain elicit similar cortical responses. These
      results have implications for the design and interpretation of brain-imaging
      studies of visceral pain. They not only contribute to our understanding of the
      processing of visceral pain, but also have clinical implications for the
      management of chronic pain states.

PMID- 15940618
TI  - Vitamin B6 intake, alcohol consumption, and colorectal cancer: a longitudinal
      population-based cohort of women.
AB  - BACKGROUND & AIMS: Vitamin B6 has a crucial role in 1-carbon metabolism, which
      involves DNA synthesis and DNA methylation. Aberrations in these processes have
      been implicated in colorectal carcinogenesis. We examined the association between
      long-term dietary vitamin B6 intake and risk of colorectal cancer and whether
      this association is modified by consumption of alcohol, which may disrupt 1
      carbon metabolism. METHODS: Our study population comprised 61,433 women in the
      population-based Swedish Mammography Cohort. The women were aged 40 to 76 years,
      had no history of cancer, and completed a food-frequency questionnaire at
      baseline in 1987-1990. Dietary information was updated in 1997. During a mean
      follow-up of 14.8 years, 805 incident colorectal cancer cases were diagnosed.
      RESULTS: After controlling for age and other potential confounders, long-term
      intake of dietary vitamin B6 was significantly inversely associated with risk of
      colorectal cancer (P value for trend = .002). Compared with women in the lowest
      quintile of vitamin B6 intake, those in the highest quintile had a 34% lower risk
      (multivariate rate ratio, 0.66; 95% confidence interval, 0.50-0.86). The
      association was most pronounced among women with moderate to high alcohol
      consumption. The multivariate rate ratio of colorectal cancer comparing extreme
      quintiles of vitamin B6 intake was 0.28 (95% confidence interval, 0.13-0.59)
      among women who consumed > or = 30 g/wk of alcohol (approximately equivalent to 2
      drinks per week). CONCLUSIONS: Findings of this study suggest that vitamin B6 may
      play a role in the prevention of colorectal cancer, particularly among women who
      drink alcohol.

PMID- 15940619
TI  - Helicobacter pylori "test and treat" or endoscopy for managing dyspepsia: an
      individual patient data meta-analysis.
AB  - BACKGROUND & AIMS: Helicobacter pylori "test and treat" has been recommended for
      the management of young dyspeptic patients without alarm symptoms, and trials
      have suggested that it is as effective as endoscopy. However, none of these
      trials have had sufficient sample size to confirm that "test and treat" costs
      less or to detect small differences in effect. A collaborative group has
      prospectively registered trials comparing prompt endoscopy with a "test and
      treat" approach, with the aim of performing an individual patient data meta
      analysis of both effect and resource utilization data. METHODS: Researchers
      provided data for meta-analysis, pooling effects of interventions on individual
      dyspepsia symptoms. Standardized unit costs were applied to resource utilization,
      and net benefit was calculated at patient level. Effects, costs, and net benefit
      were then pooled at study level. RESULTS: Five trials were identified, containing
      1924 patients (946 endoscopy [mean age, 40 years], 978 "test and treat" [mean
      age, 41 years]). The relative risk (RR) of remaining symptomatic after 1 year was
      reduced with endoscopy compared with "test and treat" (RR = 0.95; 95% confidence
      interval [CI]: 0.92-0.99). "Test and treat" cost 389 dollars less per patient
      (95% CI: 275-502 dollars). Using the net benefit approach, at no realistic level
      of willingness to pay per patient symptom-free did prompt endoscopy become cost
      effective. CONCLUSIONS: Prompt endoscopy confers a small benefit in terms of cure
      of dyspepsia but costs more than "test and treat" and is not a cost-effective
      strategy for the initial management of dyspepsia.

PMID- 15940620
TI  - Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a
      prospective cohort study.
AB  - BACKGROUND & AIMS: Helicobacter pylori-negative idiopathic ulcers are
      increasingly recognized. The secular trend and long-term outcome of this
      condition are unknown. METHODS: We prospectively studied consecutive patients
      with bleeding gastroduodenal ulcers from January to December 2000. The incidence
      and etiology of ulcers during this period were compared with that between
      September 1997 and August 1998. H. pylori-negative idiopathic ulcers were defined
      as negative tests for H. pylori, no exposure to analgesics within 4 weeks, and
      absence of other risk factors for ulcers. After the ulcers had healed, patients
      with H. pylori-negative idiopathic ulcers and patients with H. pylori ulcers who
      received eradication therapy were followed up for 12 months without anti-ulcer
      drugs. RESULTS: Six hundred thirty-eight patients had bleeding ulcers: 213
      (33.4%) were H. pylori ulcers, and 120 (18.8%) were H. pylori-negative idiopathic
      ulcers (vs 480 [50.3%] H. pylori ulcers and 40 [4.2%] H. pylori-negative
      idiopathic ulcers in 1997-1998; P < .001). H. pylori-negative idiopathic ulcers
      accounted for 16.1% of patients who were admitted for bleeding and 42.4% of
      patients who bled while in the hospital (P < .0001); 28.3% of patients with H.
      pylori-negative idiopathic ulcers had histologic evidence of past H. pylori
      infection. The probability of recurrent ulcer complications in 12 months was
      13.4% (95% CI: 7.3%-19.5%) in patients with H. pylori-negative idiopathic ulcers
      and 2.5% (95% CI: 0.4%-4.6%) in patients with H. pylori ulcers who received
      eradication therapy (P = .0002). CONCLUSIONS: The incidence of H. pylori-negative
      idiopathic bleeding ulcers is rising. These ulcers are prone to recurrent
      complications.

PMID- 15940621
TI  - Increase of bone marrow-derived secretory lineage epithelial cells during
      regeneration in the human intestine.
AB  - BACKGROUND & AIMS: We have previously reported that bone marrow (BM)-derived
      cells contribute to the regeneration of the human intestinal epithelium. To
      analyze further how these cells arise, proliferate, and differentiate as
      epithelial cells, histologic analysis was conducted using endoscopic specimens.
      METHODS: Thirty biopsy specimens from 14 female, sex-mismatched BM
      transplantation recipients were examined. BM-derived cells were identified by
      fluorescent in situ hybridization (FISH) for the Y chromosome and
      immunohistochemistry. Multicolor FISH was used to exclude cell fusion. These
      cells were further analyzed for various differentiation or proliferation markers.
      RESULTS: No evidence of cell fusion was detected. BM-derived cells did not
      distribute within the crypt as stem cells and rarely expressed Musashi-1.
      However, BM-derived epithelial cells frequently expressed Ki-67, and some of
      these cells appeared as pairs of adjacent cells. These cells also expressed
      markers of all 4 lineages of terminally differentiated cells. During regeneration
      following graft-vs-host disease, the number of BM-derived cells was substantially
      increased within Ki-67-positive cells. Interestingly, the number of cells
      expressing markers for secretory lineage cells was significantly increased within
      BM-derived cells. This change was unique for BM-derived cells, resulting in a
      significantly increased proportion of BM-derived cells among secretory lineage
      cells. CONCLUSIONS: BM-derived epithelial cells arise via a mechanism other than
      cell fusion and rarely give rise to stem cells. However, a small proportion of
      these cells express proliferation markers, and a majority reside as terminally
      differentiated cells. During regeneration BM-derived cells increase as secretory
      lineage cells, thereby contributing to restore epithelial functions.

PMID- 15940622
TI  - Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory
      bowel disease.
AB  - BACKGROUND & AIMS: Regulatory CD25+ T cells (T(reg)) are effective in the
      prevention and down-regulation of inflammatory bowel disease (IBD) in animal
      models. Functional T(reg) cells are characterized by the expression of the
      transcription factor FOXP3 and show a CD4+ CD25(high) phenotype in humans. The
      aim of this study was to determine whether disease activity in IBD correlates
      with changes in frequency of T(reg) cells and their distribution in the
      intestinal mucosa. METHODS: T(reg) cells were analyzed from peripheral blood and
      from biopsy specimens of IBD patients, inflammatory controls, and healthy
      volunteers by flow cytometry (CD4+ CD25(high)), immunochemistry (FOXP3), and real
      time PCR (FOXP3). Regulatory properties of purified peripheral CD4+ CD25(high)
      T(reg) cells were determined by their suppressive effect on the proliferation of
      CD4+ CD25- T cells. RESULTS: In peripheral blood, CD4+ CD25(high) T cells from
      IBD patients retain their suppressive activity. CD4+ CD25(high) and FOXP3+ T(reg)
      cells are increased during remission but decreased during active disease. This
      contrasts with their strong increase in peripheral blood of patients with acute
      diverticulitis. Different than peripheral blood, inflamed IBD mucosa contains an
      increased number of CD4+ CD25(high) T cells, FOXP3+ T cells, and transcripts for
      FOXP3 compared with noninflamed mucosa. However, the increase of FOXP3+ T cells
      in IBD lesions is significantly lower compared with inflammatory controls.
      CONCLUSIONS: The frequency of CD4+ CD25+ T(reg) cells varies with IBD activity.
      Active IBD is not associated with a functional defect but with a contraction of
      the peripheral blood T reg pool and an only moderate expansion in intestinal
      lesions. Thus, compensatory mechanisms, numerically, are not successfully
      achieved in these diseases.

PMID- 15940623
TI  - Human intestinal IgA response is generated in the organized gut-associated
      lymphoid tissue but not in the lamina propria.
AB  - BACKGROUND & AIMS: The intestinal lamina propria has traditionally been viewed as
      the effector site of mucosal immune responses. However, this view has been
      challenged with the identification, in the murine lamina propria, of an in situ
      class switch DNA recombination pathway to IgA. In this study, we tested the
      hypothesis that in situ class switching occurs in the human lamina propria.
      METHODS: Immunohistochemistry was used to analyze tissue microenvironments and RT
      PCR to look for molecular evidence of Ig class switching and to track clonally
      related cells of B lineage. RESULTS: We found no evidence of proliferation of
      either lamina propria CD20+ or CD19+ cells or evidence of activation-induced
      cytidine deaminase mRNA expression outside the organized gut-associated lymphoid
      tissue, although I alpha-C alpha immunoglobulin germ-line gene transcript
      expression could be identified in the lamina propria. We identified clonally
      related cells, including IgA and IgM isotype-switched variants, in multiple
      samples known to be free of activation-induced cytidine deaminase, organized
      lymphoid tissue, or cellular proliferation. For 4 groups of cells, the patterns
      of somatic mutations on the rearranged IgV(H)5 gene segment were more similar
      between cells from distant sites than from their immediate neighbors, implying
      dissemination of cells from a common set of precursors. CONCLUSIONS: Our data are
      inconsistent with a model in which precursors of human IgA-secreting plasma cells
      are induced or expanded in the lamina propria. The human lamina propria is
      therefore likely to solely be an effector site of intestinal secretory IgA
      responses that originate from the organized gut-associated lymphoid tissues.

PMID- 15940624
TI  - Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor
      of sustained response to therapy.
AB  - BACKGROUND & AIMS: This study aimed to determine whether intrahepatic hepatitis B
      virus (HBV) covalently closed circular (ccc) DNA and total HBV DNA levels at the
      end of therapy would predict sustained response to therapy. METHODS: Hepatitis B
      e antigen (HBeAg)-positive chronic hepatitis B patients receiving either
      lamivudine monotherapy or combination of peginterferon and lamivudine had liver
      biopsy at the end of 1 year therapy and were followed for 52 more weeks after
      cessation of therapy. Serum HBV DNA, intrahepatic HBV ccc DNA, and total HBV DNA
      levels were determined. RESULTS: Forty-seven patients, including 34 males and 13
      females, were studied. Twenty-seven patients received combination therapy, and 20
      patients received lamivudine monotherapy. Twenty-nine patients had end-of
      treatment virologic response, and 15 patients had sustained response 52 weeks
      after therapy. At the end of treatment, log serum HBV DNA levels correlated well
      with log intrahepatic HBV cccDNA and log intrahepatic total HBV DNA levels. Log
      intrahepatic cccDNA and log intrahepatic total DNA levels were significantly
      lower among patients with sustained virologic response. The adjusted odds ratio
      for log cccDNA was 5.3 (95% CI: 1.5-18.2, P = .009) and, for log intrahepatic HBV
      DNA, was 4.4 (95% CI: 1.3-14.7, P = .015) to predict sustained virologic
      response. Using log cccDNA at -0.80 copies/genome equivalent as cutoff, the
      sensitivity, specificity, and positive and negative predictive values and
      accuracy of predicting sustained virologic response were 73%, 78%, 56%, 86%, and
      77% respectively. CONCLUSIONS: Intrahepatic HBV cccDNA and intrahepatic total HBV
      DNA levels at the end of therapy are superior to serum HBV DNA as surrogates of
      sustained virologic response.

PMID- 15940625
TI  - Sampling variability of liver biopsy in nonalcoholic fatty liver disease.
AB  - BACKGROUND & AIMS: In nonalcoholic fatty liver disease (NAFLD), the distinction
      between steatosis and steatohepatitis (NASH) and the assessment of the severity
      of the disease rely on liver histology alone. The aim of this study was to assess
      the sampling error of liver biopsy and its impact on the diagnosis and staging of
      NASH. METHODS: Fifty-one patients with NAFLD underwent percutaneous liver biopsy
      with 2 samples collected. The agreement between paired biopsy specimens was
      assessed by the percentage of discordant results and by the kappa reliability
      test. RESULTS: No features displayed high agreement; substantial agreement was
      only seen for steatosis grade; moderate agreement for hepatocyte ballooning and
      perisinusoidal fibrosis; fair agreement for Mallory bodies; acidophilic bodies
      and lobular inflammation displayed only slight agreement. Overall, the
      discordance rate for the presence of hepatocyte ballooning was 18%, and
      ballooning would have been missed in 24% of patients had only 1 biopsy been
      performed. The negative predictive value of a single biopsy for the diagnosis of
      NASH was at best 0.74. Discordance of 1 stage or more was 41%. Six of 17 patients
      with bridging fibrosis (35%) on 1 sample had only mild or no fibrosis on the
      other and therefore could have been under staged with only 1 biopsy.
      Intraobserver variability was systematically lower than sampling variability and
      therefore could not account for most of the sampling error. CONCLUSIONS:
      Histologic lesions of NASH are unevenly distributed throughout the liver
      parenchyma; therefore, sampling error of liver biopsy can result in substantial
      misdiagnosis and staging inaccuracies.

PMID- 15940626
TI  - Oncogenic K-ras stimulates Wnt signaling in colon cancer through inhibition of
      GSK-3beta.
AB  - BACKGROUND & AIMS: Two key genetic events underlying the development of colon
      cancer are activation of the K-ras and Wnt signaling pathways. We have previously
      shown that these 2 pathways can cooperate to regulate vascular endothelial growth
      factor (VEGF) gene expression. The goal of this study was to define the molecular
      basis for this interaction. METHODS: The effects of K-ras(Val12) on VEGF and T
      cell factor 4 (TCF-4) promoter activity, nuclear levels of beta-catenin and beta
      catenin/TCF-4 complexes, glycogen synthase kinase 3beta (GSK-3beta)
      phosphorylation, and GSK-3beta kinase activity were measured. LY294002 and
      PD98059 were used to define the role of specific ras effector pathways. RESULTS:
      Oncogenic K-ras up-regulated the activity of the VEGF promoter, and selective
      mutagenesis of TCF-4 binding sites significantly blocked this induction. K
      ras(Val12) also induced the activity of a heterologous TCF-4 reporter construct
      in Caco-2 and HeLa cells. LY294002 and dominant negative phosphatidylinositol 3
      kinase nearly completely blocked this induction. K-ras(Val12) increased the
      stability of beta-catenin, the levels of nuclear beta-catenin, and the formation
      of nuclear beta-catenin/TCF-4 complexes, and these effects were also blocked by
      LY294002. Finally, K-ras(Val12) inhibited the kinase activity of total cellular
      GSK-3beta and GSK-3beta complexed with Axin. This effect was not mediated through
      phosphorylation at serine 9 but did depend on phosphatidylinositol 3-kinase.
      CONCLUSIONS: Our results suggest a unique cooperative interaction between 2
      critical oncogenic pathways in colorectal tumorigenesis and highlight the pivotal
      role of GSK-3beta.

PMID- 15940627
TI  - Poly(ADP-ribose) polymerase-1 is a component of the oncogenic T-cell factor
      4/beta-catenin complex.
AB  - BACKGROUND & AIMS: T-cell factor (TCF)-4 regulates a certain set of genes related
      to growth and differentiation of intestinal epithelial cells. Aberrant
      transactivation of these TCF-4-regulated genes by beta-catenin protein plays a
      crucial role in early intestinal carcinogenesis, and the transcriptional
      machinery of the TCF-4/beta-catenin complex is likely to contain targets for
      molecular therapy. We explored the molecular composition of the TCF-4/beta
      catenin transcriptional complex by means of proteomics. METHODS & RESULTS: A
      protein of approximately 112 kilodaltons was consistently coimmunoprecipitated
      with FLAG-tagged TCF-4 transiently expressed in HEK293 cells, and the protein was
      identified by mass spectrometry as poly(ADP-ribose) polymerase-1 (PARP-1). PARP-1
      physically interacted with TCF-4 and augmented the transcriptional activity of
      the beta-catenin/TCF-4 complex. Knockdown of PARP-1 by RNA interference
      significantly suppressed both transcriptional activity and proliferation by
      colorectal cancer cells. Auto-polyADP-ribosylation of the PARP-1 protein induced
      by DNA damage inhibited the functional interaction of PARP-1 with TCF-4. PARP-1
      was overexpressed in the intestinal adenomas of patients with familial
      adenomatous polyposis and multiple intestinal polyposis mice. The expression of
      PARP-1 was closely associated with the accumulation of beta-catenin and with the
      undifferentiated status of intestinal epithelial cells. CONCLUSIONS: In this
      study, we identified PARP-1 as a novel coactivator of the beta-catenin/TCF-4
      complex. Although PARP-1 has been believed to play a protective role against
      carcinogenesis, these expression patterns and functional properties of PARP-1
      were highly suggestive of its participation in early colorectal carcinogenesis.

PMID- 15940628
TI  - Helicobacter felis eradication restores normal architecture and inhibits gastric
      cancer progression in C57BL/6 mice.
AB  - BACKGROUND & AIMS: The impact of Helicobacter eradication therapy on the
      progression or regression of gastric lesions is poorly defined. This study
      examined the effects of eradication therapy on inflammation, atrophy, metaplasia,
      dysplasia, and cancer progression. METHODS: C57BL/6 mice were infected with
      Helicobacter felis and received bacterial eradication therapy after 2, 6, or 12
      months of infection. The gastric mucosa was examined at early, mid, and late
      intervals after eradication and graded for histology, expression pattern of alpha
      catenin and beta-catenin, and IQGAP1. RESULTS: Eradication of Helicobacter
      infection after 2 or 6 months of infection led to a regression of inflammation,
      restoration of parietal cell mass, and reestablishment of normal architecture.
      Progression to adenocarcinoma was prevented. Bacterial eradication at 1 year was
      associated with the reappearance of parietal cells, partial regression of
      inflammation, and restoration of architecture. Hyperplasia scores significantly
      improved, and dysplasia did not progress. Infected mice developed antral
      adenocarcinoma and gastric outlet obstruction by 24 months. Only 30% of the mice
      receiving bacterial eradication therapy at 12 months developed antral carcinoma.
      Bacterial eradication at any time during the first year of infection prevented
      death due to gastric outlet obstruction. The expression pattern of alpha-catenin,
      beta-catenin, and IQGAP1 varied with cell type and paralleled histologic changes.
      CONCLUSIONS: Inflammation, metaplasia, and dysplasia are reversible with early
      eradication therapy; progression of dysplasia was arrested with eradication
      therapy given as late as 1 year and prevented gastric cancer-related deaths.

PMID- 15940629
TI  - A model of neural cross-talk and irritation in the pelvis: implications for the
      overlap of chronic pelvic pain disorders.
AB  - BACKGROUND & AIMS: Irritable bowel syndrome, interstitial cystitis, and other
      chronic pelvic pain (CPP) disorders often occur concomitantly. Neural cross-talk
      may play a role in the overlap of CPP disorders via the convergence of pelvic
      afferents. We investigated the hypothesis that afferent irritation of one pelvic
      organ may adversely influence and sensitize another via neural interactions.
      METHODS: We measured pelvic organ smooth muscle and striated muscle reflexes
      during micturition and colorectal distention (CRD) in urethane-anesthetized rats.
      The effects of acute cystitis on distal colonic sensory thresholds to CRD and the
      effects of acute colonic irritation on micturition parameters were assessed.
      RESULTS: External urethral sphincter (EUS) electromyography (EMG) was typical for
      the rat, with phasic firing during micturition. External anal sphincter EMG also
      showed phasic firing during micturition in synchrony with EUS activity but, in
      addition, showed both tonic bursts and phasic firing independent of EUS activity.
      Before bladder irritation, graded CRDs to 40 cm H2O produced no notable changes
      in abdominal wall EMG activity. Following acute bladder irritation, dramatic
      increases in abdominal wall EMG activity in response to CRD were observed at much
      lower distention pressures, indicating colonic afferent sensitization.
      Analogously, following acute colonic irritation, bladder contraction frequency
      increased 66%, suggesting sensitization of lower urinary tract afferents.
      CONCLUSIONS: We report compelling evidence of bidirectional cross-sensitization
      of the colon and lower urinary tract in a novel experimental model. This cross
      sensitization may account for the substantial overlap of CPP disorders; however,
      further studies are needed to fully characterize these pathways.

PMID- 15940630
TI  - Synergistic inhibitory effects of gastrin and histamine receptor antagonists on
      Helicobacter-induced gastric cancer.
AB  - BACKGROUND & AIMS: Apart from its importance as an acid secretogogue, the role of
      histamine as a downstream target of gastrin has not been fully explored. Previous
      studies have shown that the combination of hypergastrinemia and Helicobacter
      infection resulted in accelerated gastric cancer in mice. We used this model to
      examine the role of cholecystokinin 2 (CCK2)/gastrin receptor and histamine H2
      receptor signaling in the development of gastric atrophy and cancer. METHODS:
      Male hypergastrinemic mice (INS-GAS mice) were infected with Helicobacter felis
      and given the CCK2/gastrin receptor antagonist YF476 and/or the histamine H2
      receptor antagonist loxtidine for 3 or 6 months. In addition, mice were treated
      with omeprazole alone or in combination with either YF476 or loxtidine for 3
      months. RESULTS: Mice treated with YF476 or loxtidine alone showed partial
      suppression of both gastric acid secretion and progression to neoplasia. The
      combination of YF476 plus loxtidine treatment resulted in nearly complete
      inhibition of both parameters. YF476 and/or loxtidine treatment did not alter the
      overall level of H. felis colonization but did result in significant down
      regulation of the growth factors regenerating gene I and amphiregulin. Loxtidine
      treatment, with or without YF476, induced a mild shift in T-helper cell
      polarization. In contrast, omeprazole treatment resulted in mild progression of
      gastric hyperplasia/dysplasia, which was ameliorated by the addition of YF476 or
      loxtidine. CONCLUSIONS: The combination of CCK2/gastrin- and histamine H2
      receptor antagonists has synergistic inhibitory effects on development of gastric
      atrophy and cancer in H. felis/INS-GAS mice, while the proton pump inhibitor
      showed no such effects. These results support an important role for the gastrin
      histamine axis in Helicobacter-induced gastric carcinogenesis.

PMID- 15940631
TI  - A regenerative role for bone marrow following experimental colitis: contribution
      to neovasculogenesis and myofibroblasts.
AB  - BACKGROUND & AIMS: Bone marrow (BM) cells form differentiated adult lineages
      within nonhematopoietic tissues, with a heightened propensity with increasing
      regenerative pressure dictated by disease. We have previously shown that BM cells
      engraft into the gut and contribute substantially to the subepithelial intestinal
      myofibroblast population in the lamina propria. To investigate the reparative
      capacity of BM in inflammatory bowel disease (IBD), a well-established model of
      experimental colitis was used. METHODS: Lethally irradiated female mice were
      rescued by a BM transplant from male donors. Colitis was induced 6 weeks
      posttransplantation by injection of trinitrobenzene sulfonic acid (TNBS), and
      tissues were analyzed 1-14 days later. Donor-derived cells were detected by in
      situ hybridization using a Y chromosome-specific probe, and their phenotype was
      determined by immunohistochemistry. RESULTS: TNBS-induced colitis was manifest as
      patchy lesions that increased in severity between days 1 and 8, and the mucosa
      gradually regenerated between days 8 and 14. The contribution of BM to intestinal
      myofibroblasts was significantly increased in regions of colitis compared with
      noninflamed regions. Furthermore, BM-derived endothelial cells, pericytes, and
      vascular smooth muscle cells were frequently interspersed throughout blood
      vessels, suggesting that these cells facilitate angiogenesis in tissue repair,
      substantiated by a significant increase in the incidence of BM-derived vascular
      smooth muscle cells in colitic compared with noninflamed regions. Blood vessels
      formed entirely from BM-derived cells were also seen, suggesting a role for BM in
      neovasculogenesis. CONCLUSIONS: Our data show that BM contributes to multiple
      intestinal cell lineages in colitis, with an important function in tissue
      regeneration and vasculogenesis after injury.

PMID- 15940632
TI  - Rectal instillation of butyrate provides a novel clinically relevant model of
      noninflammatory colonic hypersensitivity in rats.
AB  - BACKGROUND & AIMS: The treatment of irritable bowel syndrome (IBS), characterized
      by abdominal pain and bloating, is empirical and often poorly efficient. Research
      lacks suitable models for studying the pathophysiologic mechanisms of the colonic
      hypersensitivity and new pharmacologic targets. The present study aimed to
      develop a novel model of colonic hypersensitivity possessing several of the
      characteristics encountered in patients with IBS. METHODS: Rats received enemas
      of a butyrate solution (8-1000 mmol/L) twice daily for 3 days. A time course was
      determined for colonic hypersensitivity (colorectal distention test) and referred
      cutaneous lumbar hyperalgesia (von Frey hairs). Macroscopic and histologic
      analyses were performed on colonic mucosa. The efficacy of morphine, U50488H (a
      kappa opioid agonist), and trimebutine on the 2 pain parameters was determined.
      Finally, the involvement of peptidergic C-fibers was evaluated using capsaicin
      pretreated animals and treatments with calcitonin gene-related peptide (CGRP) and
      neurokinin 1 receptor antagonists. RESULTS: Butyrate enemas induced a sustained,
      concentration-dependent colonic hypersensitivity and, to a lesser extent, a
      referred cutaneous mechanical hyperalgesia, particularly in female rats, but no
      macroscopic and histologic modifications of the colonic mucosa, as observed in
      patients with IBS. Both pain parameters were sensitive to morphine, U50488H,
      trimebutine, neonatal capsaicin treatment, and the CGRP receptor antagonist but
      not to the neurokinin 1 receptor antagonist. CONCLUSIONS: These results present
      our noninflammatory model of chronic colonic hypersensitivity as a useful novel
      tool for studying IBS. The CGRP receptor antagonist-induced reduction of colonic
      hypersensitivity suggests that CGRP receptors may provide a promising target for
      treatment of IBS.

PMID- 15940633
TI  - N-methyl-D-aspartate receptors mediate endogenous opioid release in enteric
      neurons after abdominal surgery.
AB  - BACKGROUND & AIMS: We tested the hypothesis that N-methyl-D-aspartate (NMDA)
      receptors mediate surgery-induced opioid release in enteric neurons. METHODS: We
      used mu opioid receptor (muOR) internalization as a measure of opioid release
      with immunohistochemistry and confocal microscopy. MuOR internalization was
      quantified in enteric neurons from nondenervated and denervated ileal segments of
      guinea pig after abdominal laparotomy with and without pretreatment with NMDA
      receptor antagonists acting at different recognition sites (+)-5-methyl-10,11
      dihydro-5H-dibenzo [a,b] cyclohepten-5,10-imine (MK-801) or (D) 2-amino-5
      phosphopenoic acid (AP-5) at .5, 1 mg/kg; 8-chloro-4-hydroxy-1-oxo-1,2
      dihydropyridazinol [4,5-]quinoline-5-oxide choline (MRZ 2/576) or 8-chloro-1,4
      dioxo-1,2,3,4-tetrahydropyridazinol [4,5-]quinoline choline salt (MRZ 2/596) at
      .3, 1 mg/kg, or with an antagonist for the alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) receptors, 6-cyano-7-nitroquinoxaline-2,3-dione
      (1, 3 mg/kg). To determine whether NMDA stimulation induces opioid release, (1)
      ilea were exposed to NMDA (100 micromol/L) and D-serine (10 micromol/L) with or
      without the antagonist MK-801 or AP-5 (50 micromol/L); and (2) neuromuscular
      preparations of the ileum were stimulated electrically (20 Hz, 20 min) with or
      without MK-801 or AP-5 (50 micromol/L). RESULTS: MuOR endocytosis induced by
      abdominal laparotomy was inhibited significantly by NMDA-receptor antagonists in
      nondenervated and denervated ileal segments, but not by the AMPA-receptor
      antagonist. MuOR endocytosis in neurons exposed to NMDA or electrical stimulation
      was prevented by NMDA-R antagonists. CONCLUSIONS: Abdominal laparotomy evokes
      local release of glutamate that results in endogenous opioid release through the
      activation of peripheral NMDA receptors. This suggests an interaction between the
      glutamatergic and opioid systems in response to the noxious and perhaps
      mechanosensory stimulation of surgery.

PMID- 15940634
TI  - Antibodies to CBir1 flagellin define a unique response that is associated
      independently with complicated Crohn's disease.
AB  - BACKGROUND & AIMS: Antibody responses to certain microbial antigens define
      heterogeneous groups of Crohn's patients; multiple and high-level responses to
      these antigens are associated with aggressive clinical phenotypes. The flagellin,
      CBir1, identified by investigations in the C3H/HeJBir mouse model, has been
      identified as a dominant antigen capable of inducing colitis in mice and
      eliciting antibody responses in a subpopulation of patients with Crohn's disease
      (CD). The aim of this study was to evaluate serum response to CBir1 flagellin in
      CD patients and to compare this response to responses defined previously to
      oligomannan (anti-Saccharomyces cerevisiae antibody), I2, OmpC, and neutrophil
      nuclear autoantigens (pANCA), and to determine anti-CBir1-associated phenotypes.
      METHODS: A total of 484 sera from the Cedars Sinai Medical Center repository,
      previously typed for anti-Saccharomyces cerevisiae antibody, anti-I2, anti-OmpC,
      and pANCA were tested for anti-CBir1 by enzyme-linked immunosorbent assay, and
      results were assessed for clinical phenotype associations. RESULTS: The presence
      and level of immunoglobulin G anti-CBir1 were associated with CD independently.
      Anti-CBir1 was present in all antibody subgroups and expression increased in
      parallel with increases in the number of antibody responses. pANCA+ CD patients
      were more reactive to CBir1 than were pANCA+ ulcerative colitis patients. Anti
      CBir1 expression is associated independently with small-bowel, internal
      penetrating, and fibrostenosing disease features. CONCLUSIONS: Serum responses to
      CBir1 independently identify a unique subset of patients with complicated CD.
      This bacterial antigen was identified in a murine model and has a similar pattern
      of aberrant reactivity in a subset of CD patients.

PMID- 15940635
TI  - Use of adenovirus-delivered siRNA to target oncoprotein p28GANK in hepatocellular
      carcinoma.
AB  - BACKGROUND & AIMS: RNA interference (RNAi) is a powerful tool to silence gene
      expression. The adenoviral vector expressing small interfering RNA (siRNA) is
      highly effective in mammalian cells. However, its potential use as a therapeutic
      tool to target an oncogene specifically remains to be seen. We applied the
      adenovirus-delivered siRNA (AdSiRNA) to inhibit a hepatocellular carcinoma (HCC)
      oncogene, p28GANK, in HCC cell lines and investigated its antitumor effects.
      METHODS: The T7-RNA polymerase system was used to screen the specific target
      site. Double-strand oligonucleotide for transcription of short hairpin RNA was
      constructed into the adenoviral vector. Four HCC cell lines were infected with
      the RNAi-containing adenovirus. The RNAi effects on HCC were studied in cultured
      cells as well as in animal models. RESULTS: p28GANK expression was suppressed by
      up to 80% in HCC cells. Depletion of p28GANK inhibited HCC cell growth and
      tumorigenesis, enhanced dephosphorylation of RB1, and decreased transcription
      activity of E2F-1 in HuH-7 cells. Furthermore, depletion of p28GANK induced
      caspase-8- and caspase-9-mediated apoptosis of HCC cells. Finally, targeting
      p28GANK by adenovirus injection inhibited the growth of established tumors in
      nude mice. CONCLUSIONS: This study shows that the T7-system screening-based
      AdSiRNA can be used successfully to silence an oncogene. We proved the
      therapeutic potential of AdSiRNA on the treatment of HCC by targeting p28GANK.
      Our results indicate that p28GANK may serve as a novel therapeutic target for
      treating HCC.

PMID- 15940636
TI  - Interferon-gamma inhibits hepatitis B virus-induced NF-kappaB activation through
      nuclear localization of NF-kappaB-inducing kinase.
AB  - BACKGROUND & AIMS: Nuclear factor-kappaB (NF-kappaB) signaling pathway is an
      important regulating pathway in liver diseases, including hepatocellular
      carcinoma. In our study, immunohistochemical analysis showed that NF-kappaB
      inducing kinase (NIK), an upstream kinase of IkappaB kinases, nuclear
      localization occurs only in liver tissues obtained from hepatitis B surface
      antigen (HBsAg)(+) patients but not in tissues from HBsAg(-) patients. The aim of
      the present study was to identify the inducer of NIK nuclear localization and
      determine whether the NIK nuclear localization affects the hepatitis B virus
      (HBV)-mediated NF-kappaB activation. METHODS: The experiments were performed on
      HepG2.2.15 cells and on HepG2 cells transfected with pHBV1.2x, a plasmid encoding
      all HBV messages, using NF-kappaB-dependent luciferase reporter gene assay,
      electrophoretic mobility shift assay, immunoblot analysis, and fluorescent
      microscopy analysis. RESULTS: HBV induced NIK-dependent NF-kappaB activation.
      However, interferon (IFN)-gamma induced NIK nuclear localization and inhibited NF
      kappaB activation in HepG2.2.15 cells and in HepG2 cells transfected with
      pHBV1.2x. When NIK nuclear localization was inhibited by deletion of nuclear
      localization signal on NIK, IFN-gamma did not induce the NIK nuclear localization
      and did not inhibit NF-kappaB activation. CONCLUSIONS: IFN-gamma selectively
      inhibits HBV-mediated NF-kappaB activation. This inhibition is accomplished by
      NIK nuclear localization, which is a novel mechanism of NF-kappaB inhibition.

PMID- 15940637
TI  - Interleukin-6 contributes to Mcl-1 up-regulation and TRAIL resistance via an Akt
      signaling pathway in cholangiocarcinoma cells.
AB  - BACKGROUND & AIMS: Cholangiocarcinomas often arise within a background of chronic
      inflammation suggesting that inflammation imparts survival signals to this
      cancer. Previous studies have also shown that the inflammatory cytokine
      interleukin (interleukin [IL]-6) contributes to survival signals in an autocrine
      fashion and that myeloid cell leukemia-1 (Mcl-1), an antiapoptotic member of the
      B-cell leukemia-2 family, is an important participant in tumor necrosis factor
      related apoptosis-inducing ligand (TRAIL) resistance in this neoplasm. The
      present study evaluated the possibility that IL-6 signaling contributes to Mcl-1
      up-regulation in cholangiocarcinoma. METHODS: Protein kinase B (Akt) and Mcl-1
      expression in human tissue was assessed by immunohistochemistry. The relationship
      between IL-6 signaling, Akt activity, and Mcl-1 expression was examined in cell
      lines. RESULTS: Immunohistochemistry showed that the serine/threonine kinase Akt
      and Mcl-1 are strongly expressed in the preneoplastic bile duct inflammatory
      disease primary sclerosing cholangitis and in human cholangiocarcinoma specimens.
      Immunoblotting showed that Akt is expressed and constitutively phosphorylated in
      3 human cholangiocarcinoma lines. Further analysis showed that treatment with
      anti-IL-6-neutralizing antiserum led to reduced Akt phosphorylation, diminished
      Mcl-1 expression, and enhanced TRAIL sensitivity. Likewise, the Akt inhibitor
      A443654.3 led to diminished signaling through the Akt pathway, decreased Mcl-1
      expression, and enhanced TRAIL-mediated apoptosis. CONCLUSIONS: These findings
      not only show that an autocrine IL-6/Akt signaling pathway enhances Mcl-1
      expression in cholangiocarcinoma but also suggest a strategy for overcoming the
      resulting apoptosis resistance.

PMID- 15940638
TI  - Early growth response-1 transcription factor is essential for ethanol-induced
      fatty liver injury in mice.
AB  - BACKGROUND & AIMS: Early growth response-1 (Egr-1), an immediate early gene/zinc
      finger transcription factor, is required for maximal stimulation of tumor
      necrosis factor alpha (TNF-alpha) transcription in response to lipopolysaccharide
      (LPS). Because chronic ethanol exposure sensitizes macrophages to LPS-stimulated
      TNF-alpha expression, we have investigated the role of Egr-1 in mediating
      increased LPS-stimulated TNF-alpha expression after chronic ethanol feeding.
      Furthermore, because TNF-alpha contributes to alcoholic liver injury, we tested
      the hypothesis that Egr-1 is required for the development of ethanol-induced
      fatty liver injury in wild type and egr-1 -/- mice. METHODS: Wild-type and egr-1 
      /- mice were fed ethanol-containing diets or pair-fed control diets for 6 weeks.
      RESULTS: Wild-type mice fed the ethanol diet developed hepatic steatosis
      characterized by micro- and macrovesicular lipid accumulation. However, egr-1 -/-
      mice did not develop steatosis after ethanol feeding. Alanine transferase and TNF
      alpha concentrations in serum were increased after ethanol feeding in wild-type
      but not egr-1 -/- mice. In wild-type mice, challenge with LPS increased Egr-1
      messenger RNA (mRNA) and DNA binding activity in liver; this response to LPS was
      enhanced after chronic ethanol feeding. LPS challenge also increased hepatic TNF
      alpha mRNA and serum TNF-alpha to a greater extent after ethanol feeding compared
      with pair-fed wild-type mice. However, chronic ethanol feeding did not enhance
      LPS-stimulated TNF-alpha mRNA or serum TNF-alpha in egr-1 -/- mice. CONCLUSIONS:
      These data show that Egr-1 contributes to increased LPS-mediated TNF-alpha
      expression after chronic ethanol and that the absence of Egr-1 prevents chronic
      ethanol-induced fatty liver, as well as increased sensitivity to LPS.

PMID- 15940639
TI  - Role of connective tissue growth factor in oval cell response during liver
      regeneration after 2-AAF/PHx in rats.
AB  - BACKGROUND & AIMS: Recruitment and proliferation of Thy-1+ oval cells is a
      hallmark of liver regeneration after 2-acetylaminofluorene (2-AAF)/partial
      hepatectomy (PHx) in rats. To understand the molecular mechanism underlying this
      process, we investigated the role of connective tissue growth factor (CTGF), one
      of the candidate genes differentially expressed in Thy-1+ oval cells, in this
      liver injury model. METHODS: Northern and Western analyses were performed to
      examine the induction of CTGF in total liver homogenate. Quantitative real-time
      polymerase chain reaction (PCR), immunofluorescent staining, and in situ
      hybridization were performed to confirm the expression and localization of CTGF
      in Thy-1+ oval cells. Finally, a known inhibitor of CTGF synthesis, Iloprost, was
      administered to 2-AAF/PHx treated rats to investigate the effect of Iloprost on
      oval cell response. RESULTS: CTGF was found to be up-regulated at both the RNA
      and protein levels and occurred concurrently with an up-regulation of
      transforming growth factor beta1 (TGF-beta1). Sorted Thy-1+ oval cells expressed
      a high level of CTGF gene in a quantitative PCR assay. Colocalization of Thy-1
      antigen and ctgf signals by in situ hybridization further confirmed that Thy-1+
      oval cells were a source of CTGF. Iloprost administration blocked CTGF induction
      in treated animals but did not affect TGF-beta1 expression. The inhibition of
      CTGF induction by Iloprost was associated with a significant decrease in oval
      cell proliferation and a lower level of alpha-fetoprotein expression as compared
      with control animals. CONCLUSIONS: These results show that CTGF induction is
      important for robust oval cell response after 2-AAF/PHx treatment in rats.

PMID- 15940640
TI  - Long-term extensive expansion of mouse hepatic stem/progenitor cells in a novel
      serum-free culture system.
AB  - BACKGROUND & AIMS: The liver has high regenerative potential. We attempted to
      establish a novel culture system for extensive expansion of fetal mouse hepatic
      stem/progenitor cells and to characterize cultured cells. METHODS: Hepatic
      spheroids collected from 6-day floating cultures were cultured on collagen-coated
      dishes in serum-free conditions in medium containing growth factors. Cultured
      cells were mainly characterized by immunocytochemistry and flow cytometry or
      transplanted into adult mice. RESULTS: Approximately 400 expanding hepatic
      spheroids were generated from every 1 x 10(6) fetal liver cells. Subsequently,
      highly replicative colonies were subcultured with maintaining colony formation on
      collagen-coated dishes. These colonies consisted of small immature alpha
      fetoprotein-positive cells and hepatocytic and cholangiocytic lineage-committed
      cells. The immature alpha-fetoprotein-positive cells could be expanded in a
      reproducible manner at least 5 x 10(5)-fold (which involved at least 30 passages
      over >6 months) without losing differentiation potential. Flow cytometric
      analysis showed that all cultured cells expressed CD49f, but not CD34, Thy-1, c
      kit, or CD45. Nearly 15% of the cells expressed Sca-1, and approximately 5%-20%
      of the cells were side population cells. Both sorted side population cells and
      Sca-1-positive cells (especially side population cells) produced a large number
      of alpha-fetoprotein-positive cells and lineage-committed cells. Expanded cells
      had bidirectional differentiation potential and improved serum albumin levels in
      mice with severe liver damage. CONCLUSIONS: Long-term extensive expansion of
      transplantable hepatic stem/progenitor cells was reproducibly achieved in a novel
      serum-free culture system. Moreover, this culture system yielded side population
      and Sca-1-positive cell populations that included hepatic stem/progenitor cells
      with differentiation and proliferation properties.

PMID- 15940641
TI  - Cytokines and peroxisome proliferator-activated receptor gamma ligand regulate
      phagocytosis by pancreatic stellate cells.
AB  - BACKGROUND & AIMS: Pancreatic stellate cells have been characterized as the major
      source of extracellular matrix and cytokine production in the pancreas. This
      study showed that pancreatic stellate cells have a phagocytic function. METHODS:
      The morphological features of periacinar phagocytic cells were investigated by
      immunohistochemically staining serial sections of the pancreas from male WBN/Kob
      rats and an animal model of acute pancreatitis for glial fibrillary acidic
      protein and alpha-smooth muscle actin. Pancreatic stellate cells were assayed for
      phagocytic activity by incubating them with senescent polymorphonuclear
      neutrophils or fluorescence-labeled latex beads in the presence or absence of
      cytokines, growth factors, and peroxisome proliferator-activated receptor gamma
      ligand. The role of CD36 and peroxisome proliferator-activated receptor gamma in
      phagocytosis was investigated by blocking endogenous CD36 and peroxisome
      proliferator-activated receptor gamma activity with anti-CD36 antibody and
      peroxisome proliferator-activated receptor gamma small interfering RNAs,
      respectively. RESULTS: Phagocytic cells were observed in areas of inflammation,
      and they were identical to the glial fibrillary acidic protein-positive and alpha
      smooth muscle actin-positive cells, thus suggesting that they were pancreatic
      stellate cells. Aged polymorphonuclear neutrophils were ingested into the
      cytoplasm of the pancreatic stellate cells. Transforming growth factor beta,
      tumor necrosis factor alpha, and interleukin 1beta decreased the phagocytic
      activity of pancreatic stellate cells, whereas troglitazone induced a dose
      dependent increase in both phagocytic activity and expression of CD36. Blockade
      of CD36 reduced troglitazone-induced phagocytosis. Silencing of the peroxisome
      proliferator-activated receptor gamma gene decreased phagocytosis and expression
      of CD36. CONCLUSIONS: Pancreatic stellate cells act as resident phagocytic cells,
      and CD36 promotes troglitazone-induced phagocytic activity via peroxisome
      proliferator-activated receptor gamma transactivation. Because phagocytosis is
      essential to limit the extent of inflammation, enhancement of phagocytic activity
      may provide an important approach to the treatment of pancreatic diseases.

PMID- 15940642
TI  - Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy.
AB  - BACKGROUND & AIMS: Confocal laser endomicroscopy enables subsurface microscopic
      imaging of living tissue during ongoing endoscopy. This case report describes the
      in vivo detection of Helicobacter pylori by endomicroscopy. METHODS:
      Endomicroscopy (Pentax, Tokyo, EC-3870CIFK) was performed by using two different
      contrast stains: Topical Acriflavine in addition to intravenously applied
      fluorescein netted the surface and allowed identification of focal accumulation
      of Helicobacter pylori at the surface and in deeper layer of the gastric
      epithelium. Biopsies were performed at the antrum and corpus for urease testing
      and histology. In addition, biopsies were cultured for Helicobacter pylori.
      Cultured bacteria were re-assessed ex vivo using confocal microscopy with and
      without acriflavine staining. RESULTS: Helicobacter pylori infection could be
      detected in a 70-year-old male by endomicroscopy. Accumulated, as well as single
      bacteria, could be observed and the distinct shape and flagella of Helicobacter
      pylori could be identified. Helicobacter pylori infection was proved by
      histology. Furthermore, ex vivo examination of cultures proved the presence of
      Helicobacter pylori and the active uptake of acriflavine into the bacteria.
      CONCLUSIONS: Endomicroscopy is a new diagnostic approach, which enables the
      immediate diagnosis of Helicobacter pylori in vivo during standard video
      endoscopy.

PMID- 15940643
TI  - Molecular analysis to detect pancreatic ductal adenocarcinoma in high-risk
      groups.
AB  - BACKGROUND & AIMS: Screening of high-risk groups for pancreatic cancer has not
      been adopted because of concerns regarding specificity and sensitivity.
      Suitability of a combination of 3 novel molecular screening techniques was
      investigated. METHODS: Pancreatic juice was extracted from 146 patients with
      pancreatic ductal adenocarcinoma, chronic pancreatitis, or biliary tract stones.
      p53 mutations were analyzed by using a modified yeast functional assay, K-ras
      status was analyzed using mutation-specific real-time PCR and the proportion of
      p16(INK4a) promoter methylation was estimated using comparative methylation
      specific real-time PCR. RESULTS: p53 mutations were detected in 20 of 48 (42%)
      cancer cases, none of 49 controls, and 2 of 49 (4%) patients with pancreatitis. K
      ras mutations were detected in 31 of 57 (54%) cancer patients, 13 of 61 (21%)
      controls, and 23 of 67 (34%) patients with pancreatitis. Twenty-six of 42 (62%)
      cancer patients had promoter methylation levels > 12%, compared with 3 of 24
      (13%) controls, and 2 of 26 (8%) with pancreatitis. Mutations in p53 or high
      level p16(INK4a) promoter methylation occurred in 29 of 36 (80%) patients with
      cancer, 3 of 24 (13%) controls, and 3 of 22 (13%) with pancreatitis. Three
      patients (8%) of 36 with cancer; 14 of 24 (58%) controls, and 13 of 22 (59%)
      patients with pancreatitis had no marker. The gallstone disease patients had a
      high rate of positive K-ras mutations, possibly reflecting the fact that they
      were not disease free. CONCLUSIONS: Combination molecular analysis increased the
      discrimination between patients with malignant and benign disease. This level of
      discrimination would allow patients in high-risk groups to be stratified from
      negligible risk to over 50% probability of an early cancer.

PMID- 15940644
TI  - The role of protein kinase C in gastrointestinal function and disease.

PMID- 15940645
TI  - Presentation of the AGA Distinguished Achievement Award to Henry J. Binder, MD.

PMID- 15940646
TI  - Presentation of the Julius M. Friedenwald Medal to Ralph A. Giannella, MD.

PMID- 15940647
TI  - The origin of hepatocytes.

PMID- 15940648
TI  - Infliximab for ulcerative colitis: finally some answers.

PMID- 15940649
TI  - Treatment of Crohn's disease: the "long" of it.

PMID- 15940650
TI  - Mycobacterium in Crohn's: something to ruminate about?

PMID- 15940651
TI  - Occult viral hepatitis: what is the significance?

PMID- 15940652
TI  - The GIST of a stromal tumor.

PMID- 15940654
TI  - Protease inhibitors in acute pancreatitis: lessons from the bench and failed
      clinical trials.

PMID- 15940659
TI  - Insulin resistance and hepatitis C.

PMID- 15940660
TI  - Etiology of acute pancreatitis: beware of the lipase/amylase ratio!

PMID- 15940662
TI  - Autologous hematopoietic stem cell transplantation in refractory Crohn's disease:
      a feasible therapeutic approach?

PMID- 15940663
TI  - The effect of vascular origin, oxygen, and tumour necrosis factor alpha on
      trophoblast invasion of maternal arteries in vitro.
AB  - Extravillous trophoblasts (EVTs) invade and remodel uterine spiral arteries.
      Regulatory factors may include inherent vessel susceptibility, local oxygen
      levels and tumour necrosis factor alpha (TNFalpha). We have used an in vitro
      model to investigate interstitial and endovascular invasion of myometrial spiral
      arteries from pregnant and non-pregnant uteri and also omental arteries. To model
      endovascular invasion, fluorescent-labelled EVTs were perfused into the lumen of
      these dissected vessels. For interstitial invasion, labelled EVTs were layered on
      top. Cultures were either maintained in 17% or 3% oxygen, or cultured with
      TNFalpha. The invasion of arteries from pregnant women occurred via both routes
      at 17% oxygen, with endovascular invasion more efficient than interstitial. In
      omental arteries and spiral arteries from non-pregnant women, endovascular
      invasion was limited. Endovascular and interstitial invasion were lower in all
      arteries at 3% oxygen. Typically, endovascular events were clustered, with an
      associated disruption in the adjacent endothelium and smooth muscle. A role for
      TNFalpha in limiting invasion was also supported. In conclusion, priming of
      uterine arteries may be necessary prior to EVT invasion. Oxygen is a sensitive
      regulator within this physiological model and increased invasion at higher pO2
      may explain the homing of EVT to maternal arteries rather than veins. Adequate
      vascular transformation may therefore rely on a balance between vascular
      receptivity, oxygen partial pressure, and exposure to inflammatory mediators.

PMID- 15940664
TI  - Controlled release of tethered molecules via engineered hydrogel degradation:
      model development and validation.
AB  - A statistical-co-kinetic model has been developed to predict effects of
      hydrolytic or enzymatic degradation on the macroscopic properties of hydrogels
      formed through Michael-type addition reactions. Important parameters accounted
      for by the theoretical calculations are bond cleavage kinetics, microstructural
      network characteristics such as macromer functionality and crosslinking
      efficiency, and detailed analysis of degradation products. Previous work
      indicated the validity of this modeling approach for predicting swelling behavior
      of hydrolytically degradable gels during early stages of degradation and the
      quantitative dependence of gel degradation on kinetic and structural parameters.
      The theoretical methodology is extended in the current work to predict release of
      covalently bound proteins from the network via labile bonds. Release studies of a
      network-bound fluoroscopic probe allow validation of model degradation parameters
      and indicate that macromer functionalization and network crosslinking efficiency
      can be appropriately tailored to achieve desired swelling profiles and protein
      release rates over the lifetime of the degradable gel. The effects of these
      network parameters on the timing of gel dissolution and the protein release that
      occurs during this phase of degradation are also identified, highlighting the
      utility of the developed model as a comprehensive tool for optimizing degradable
      hydrogels as matrices for drug delivery and tissue regeneration.

PMID- 15940665
TI  - Febrile seizures in the predisposed brain: a new model of temporal lobe epilepsy.
AB  - The atypical febrile seizure has important clinical implications because of its
      association with the mesial temporal lobe epilepsy syndrome, which is the most
      common of the intractable epilepsies. However, whether a causal relation exists
      between these conditions is currently unknown. We have previously shown that a
      focal cortical lesion induced in the neonatal rat predisposes to the development
      of atypical hyperthermic seizures. We show here that 86% of the lesion plus
      hyperthermia group experience development of spontaneous recurrent seizures
      recorded from the amygdala ipsilateral to the lesion. Control rats did not have
      spontaneous recurrent behavioral or electrographic seizures. Lesioned rats with
      hyperthermic seizures also showed an impaired performance on the Morris water
      maze when compared with naive control rats, suggesting mild deficits in learning
      and memory. These findings support a link between the atypical febrile seizure
      and mesial temporal lobe epilepsy, and at the same time establish a new model for
      this condition through which new preventative and therapeutic strategies can be
      tested.

PMID- 15940666
TI  - The role of CD1d-restricted NK T lymphocytes in the immune response to oral
      infection with Salmonella typhimurium.
AB  - CD1d-restricted natural killer T (NKT) cells belong to the innate-like
      lymphocytes which respond rapidly to stress and infectious challenge. We have
      studied murine CD1d-restricted NKT cells in the early immune response to virulent
      Salmonella enterica serovar Typhimurium after oral infection. In the liver and
      spleen, neutrophil and macrophage numbers had increased several-fold by day 5
      post-infection, while the frequency of B and T lymphocytes decreased. These
      cellular changes occurred independently of CD1d-restricted NKT cells, and
      further, CD1d-restricted T cells did not influence the bacterial load. However,
      in CD1d(+) mice NK1.1(+) T cells and invariant CD1d-restricted T cells were
      activated by the infection, as demonstrated by an increase in size, up-regulation
      of CD69 and production of IFN-gamma. The NK1.1 antigen was down-modulated on
      these cells during the course of infection, while TCR levels were unaffected.
      While dendritic cells (DC) up-regulated CD1d-levels upon 24 h of in vitro
      exposure to the bacteria, increased CD1d expression was not evident on DC in vivo
      during infection. Furthermore, in vitro re-stimulation of CD1d-restricted T cells
      isolated from infected mice demonstrated a significant skewing of the cytokine
      profile, with suppressed IL-4 and increased IFN-gamma production.

PMID- 15940667
TI  - Recruitment and selection of marginal zone B cells is independent of exogenous
      antigens.
AB  - Marginal zone B (MZ-B) cells of the spleen contribute significantly to the
      immunity against invasive infections with polysaccharide-encapsulated bacteria.
      Recent evidence indicates that recruitment and selection of MZ-B cells occurs on
      the basis of positive selection constraints that likely operate via B cell
      receptor (BCR) signaling. Previous studies have shown that MZ-B cells carry
      relatively shorter immunoglobulin (Ig) heavy (H) chain complementarity
      determining region 3 (H-CDR3) sequences and express BCR which are thought to be
      polyreactive. In this scenario, MZ-B cell selection proceeds via engagement of
      the BCR with exogenous (i.e. microbial gut flora-derived) and/or endogenous
      (self) antigens. Here, we studied the influence of exogenous antigens on the
      selection process of MZ-B cells using non-genetically manipulated adult germ-free
      and conventionally reared infant rats. This study was carried out by H-CDR3
      spectratype analysis of V(H)(PC7183)-encoded Ig V(H)DJ(H)-mu transcripts
      expressed by purified splenic MZ-B cells and other B cell subsets. We show that
      MZ-B cells in both adult germ-free and conventionally reared infant (14-day-old)
      rats are H-CDR3-selected cells, providing strong evidence that recruitment and
      selection of MZ-B cells is driven by self antigens.

PMID- 15940668
TI  - Association of CTLA4 polymorphism with regulatory T cell frequency.
AB  - A common single nucleotide polymorphism in CTLA4 has been linked with
      susceptibility and outcome in autoimmune and infectious diseases, respectively.
      Here, we show that this polymorphism is associated with the frequency of
      CD4(+)CD25(+) regulatory T cells in healthy human volunteers. We further show
      that, on a per cell basis, such regulatory T cells appear to be functionally
      indistinguishable across CTLA4 genotypes. These data implicate CTLA4 in
      regulatory T cell development, and provide a mechanism to account for the link
      between polymorphisms at this locus and the biological outcome of adaptive immune
      responses to self and to pathogens.

PMID- 15940669
TI  - Structural and functional differences between the promoters of independently
      expressed killer cell Ig-like receptors.
AB  - Killer Ig-like receptors (KIR) are important for the recognition and elimination
      of diseased cells by human NK cells. Myeloid leukemia patients given a
      hematopoietic stem cell transplantation, for example, benefit from KIR-mediated
      NK alloreactivity directed against the leukemia cells. To establish an effective
      NK cell repertoire, most KIR genes are expressed stochastically, independently of
      the others. However, the sequences upstream of the coding regions of these KIR
      genes are highly homologous to the recently identified KIR3DL1 promoter (91.1
      99.6% sequence identity), suggesting that they are regulated by similar if not
      identical mechanisms of transcriptional activation. We investigated the effects
      of small sequence differences between the KIR3DL1 promoter and other KIR
      promoters on transcription factor binding and promoter activity. Surprisingly,
      electrophoretic mobility shift assays and promoter-reporter assays revealed
      significant structural and functional differences in the cis-acting elements of
      these highly homologous KIR promoters, suggesting a key role for transcription
      factors in independent control of expression of specific KIR loci. Thus, the KIR
      repertoire may be shaped by a combination of both gene-specific and stochastic
      mechanisms.

PMID- 15940670
TI  - Somatic hypermutation and mismatch repair in non-B cells.
AB  - Mismatch repair contributes to hypermutation in B lymphocytes, both by increasing
      the frequency of mutations and by changing the mutational patterns. In this
      paper, we investigated whether or not mismatch repair influences activation
      induced cytidine deaminase (AID)-mediated hypermutation in a non-B lymphocyte
      line. We did so by regulating expression of MutL homologue MLH 1, which is
      essential in mismatch repair, in a kidney cell line that had been transduced by
      an AID-containing vector. Whether or not MLH1 was expressed, we found no
      difference in the mutation rates of an indicator gene. We conclude that in order
      to contribute to hypermutation, mismatch repair needs additional factors that are
      present in activated B lymphocytes, but absent in the cell line investigated.

PMID- 15940671
TI  - Cross-presentation of phage particle antigen in MHC class II and endoplasmic
      reticulum marker-positive compartments.
AB  - It has been shown that exogenous antigens can access the MHC class I pathway of
      professional antigen-processing cells. However, details as to how the MHC class I
      peptide complex forms in the presentation pathway are still poorly understood.
      Here we used MHC class I-peptide-specific antibodies to investigate the formation
      and intracellular location of class I-peptide complexes in macrophages. We
      observed that the formation of class I-peptide complexes occurs within a few
      hours and lasts for another few hours on the cell surface of macrophages
      following loading with filamentous phage particles. The class I-peptide complexes
      in the process were co-localized with MHC class II molecules and endocytic system
      markers. Moreover, endosomal compartments containing class I-peptide complexes
      were found within intracellular organelles stained by DiOC6 and calnexin. In
      addition, the cross-presentation of phage particles was transporter associated
      with antigen processing (TAP)-dependent and sensitive to proteasome inhibitors
      and NH(4)Cl. These data suggest that endocytosed phage particles may be processed
      and cross-presented in organelles positive for phagosome and endoplasmic
      reticulum (ER) markers via a classical ER MHC class I loading mechanism.

PMID- 15940672
TI  - Dectin-2 is predominantly myeloid restricted and exhibits unique activation
      dependent expression on maturing inflammatory monocytes elicited in vivo.
AB  - Dectin-2 is a recently described dendritic-cell-associated receptor, suggested to
      be involved in the initiation and maintenance of UV-induced tolerance. To
      understand the physiological relevance of the proposed functions of this C-type
      lectin-like receptor, we have generated monoclonal antibodies against its
      extracellular domain and performed a detailed study of its expression. In naive
      mice, Dectin-2 has a novel distribution pattern compared with other myeloid
      markers, but is predominantly expressed by a wide variety of tissue macrophages.
      Its expression was limited on dendritic cells and notably absent from brain
      microglia and choroid plexus or meningeal macrophages. On peripheral blood
      monocytes, Dectin-2 expression was very low on the surface but was transiently
      and markedly up-regulated on induction of inflammation in vivo using a variety of
      stimuli. This change in Dectin-2 expression occurs on 'inflammatory' monocytes
      after arrival at the inflammatory lesion as demonstrated by adoptive cell
      transfer studies, and is independent of whether the macrophages elicited by the
      stimuli ultimately expressed Dectin-2. These observations show Dectin-2
      expression to be characteristic of monocyte activation/maturation at an
      inflammatory lesion and provide a new perspective on the interpretation of Dectin
      2 function in vivo.

PMID- 15940673
TI  - Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-kappa B
      activation and IFN-beta synthesis downstream of Toll-like receptor 3 and 4.
AB  - Phosphoinositide 3-kinases (PI3K) are known to regulate Toll-like receptor (TLR)
      mediated inflammatory responses, but their impact on the different pathways of
      TLR signaling remains to be clarified. Here, we investigated the consequences of
      pharmacological inhibition of PI3K on Toll-IL-1 receptor domain-containing
      adapter-inducing IFN-beta (TRIF)-dependent signaling, which induces IFN-beta gene
      expression downstream of TLR3 and TLR4. First, treatment of monocyte-derived
      dendritic cells (DC) with wortmannin or LY294002 was found to enhance IFN-beta
      expression upon TLR3 or TLR4 engagement. In the same models of DC activation,
      PI3K inhibition increased DNA-binding activity of NF-kappaB, but not interferon
      response factor (IRF)-3, the key transcription factors required for TLR-mediated
      IFN-beta synthesis. In parallel, wortmannin-treated DC exhibited enhanced levels
      of IkappaB kinase (IKK)-alpha/beta phosphorylation and IkappaB-alpha degradation
      with a concomitant increase in NF-kappaB nuclear translocation. Experiments
      carried out in HEK 293T cells stably expressing TLR3 or TLR4 confirmed that
      inhibition of PI3K activity enhances NF-kappaB-dependent promoters as well as IFN
      beta promoter activities without interfering with transcription at the positive
      regulatory domain III-I. Furthermore, wortmannin enhanced NF-kappaB activity
      induced by TRIF overexpression in HEK 293T cells, while overexpression of
      catalytically active PI3K selectively attenuated TRIF-mediated NF-kappaB
      transcriptional activity. Finally, in co-immunoprecipitation experiments, we
      showed that PI3K physically interacted with TRIF. We conclude that inhibition of
      PI3K activity enhances TRIF-dependent NF-kappaB activity, and thereby increases
      IFN-beta synthesis elicited by TLR3 or TLR4 ligands.

PMID- 15940674
TI  - The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation
      pathway for a subset of CD8+ T cells.
AB  - The CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E is coupled to
      the KARAP/DAP12 adapter in a subset of NK cells, triggering their effector
      functions. We have studied the distribution and function of this KLR in T
      lymphocytes. Like other NK cell receptors (NKR), CD94/NKG2C was predominantly
      expressed by a CD8(+) T cell subset, though TCRgammadelta(+) NKG2C(+) and rare
      CD4(+) NKG2C(+) cells were also detected in some individuals. Coculture with the
      721.221 HLA class I-deficient lymphoma cell line transfected with HLA-E (.221
      AEH) induced IL-2Ralpha expression in CD94/NKG2C+ NK cells and a minor subset of
      CD94/NKG2C(+) T cells, promoting their proliferation; moreover, a similar
      response was triggered upon selective engagement of CD94/NKG2C with a specific
      mAb. CD8(+) TCRalphabeta CD94/NKG2C(+) T cell clones, that displayed different
      combinations of KIR and CD85j receptors, expressed KARAP/DAP12 which was co
      precipitated by an anti-CD94 mAb. Specific engagement of the KLR triggered
      cytotoxicity and cytokine production in CD94/NKG2C(+) T cell clones, inducing as
      well IL-2Ralpha expression and a proliferative response. Altogether these results
      support that CD94/NKG2C may constitute an alternative T cell activation pathway
      capable of driving the expansion and triggering the effector functions of a CTL
      subset.

PMID- 15940676
TI  - Amyloid fibril formation by the CAD domain of caspase-activated DNase.
AB  - Caspase-activated DNase (CAD) is a key protein in the process of apoptosis that
      degrades DNA through the action of caspases. Its N-terminal region, the CAD
      domain (CAD-CD), is highly conserved among CAD family proteins and is responsible
      for the interaction with its inhibitor. We report here that CAD-CD spontaneously
      aggregates to form amyloid fibrils, without a lag time, under the conditions of
      low pH (below 4) and the presence of anions. Interestingly, the secondary
      structure of CAD-CD in the fibril state comprised not only beta-sheet but also
      alpha-helix, as found in CD, FTIR, and x-ray fiber diffraction experiments.
      Aromatic side chains have a defined orientation and are in the hydrophobic
      environment occurring with the CAD-CD fibrillogenesis. These findings provide new
      insights into the architecture of amyloid fibrils.

PMID- 15940677
TI  - Minor malformations characteristic of the retinoic acid embryopathy and other
      birth outcomes in children of women exposed to topical tretinoin during early
      pregnancy.
AB  - Topical tretinoin (Retin-A) is used to treat acne and photodamaged skin. Its
      teratogenic potential is of concern due to its similarity to isotretinoin
      (Accutane), a recognized human teratogen. Through the California Teratogen
      Information Service and Clinical Research Program, between 1983 and 2003, 106
      pregnant women with first-trimester exposure to topical tretinoin were
      prospectively ascertained and followed. Birth outcomes, including pregnancy loss,
      major structural defects, and pre- and postnatal growth were compared to 389
      similarly and prospectively ascertained women with no topical tretinoin exposure
      during pregnancy. Because a distinct pattern of malformation had already been
      described for isotretinoin, we also compared exposed (n = 62) and unexposed (n =
      191) infants on the prevalence of a specific subset of minor malformations
      selected to represent the spectrum of defects comprising the retinoic acid
      embyopathy. There were no significant differences between groups in the
      proportion of pregnancies ending in spontaneous abortion (6.6% in exposed vs.
      8.5% in unexposed; P = 0.53), or infants with major structural defects (2.2% in
      exposed vs. 1.2% in unexposed; P = 0.62). In addition, the groups were similar in
      birth weight, length and head circumference, and there were no significant
      differences between groups in length of gestation. Furthermore, the prevalence of
      one or more retinoic acid-specific minor malformations did not differ
      significantly between groups (12.9% in exposed vs. 9.9% in unexposed; P = 0.51).
      First-trimester topical tretinoin exposure in this study was not associated with
      an increased risk of any adverse pregnancy outcome evaluated. Specifically, there
      was no indication that topical tretinoin is associated with an increased risk for
      minor malformations that are consistent with the retinoic acid embryopathy.
      Although it is impossible to exclude the possibility that some women/infants may
      be uniquely susceptible to topical tretinoin exposure, this study provides
      further reassurance for women who are inadvertently exposed early in pregnancy.

PMID- 15940678
TI  - Intrachromosomal triplication for the distal part of chromosome 15q.
AB  - We report the case of a boy whose karyotype at birth showed additional material
      on one chromosome 15. He underwent treatment for unilateral nephroblastoma at 6
      years old. At 23 years old, he presented with body asymmetry, facial dysmorphism,
      arachnodactyly, severe scoliosis, and mental retardation. Molecular cytogenetic
      analyses of peripheral lymphocytes demonstrated a complex mosaic with three
      clones. A major cell lineage (68%) showed a chromosome 15 with additional
      material fused to its telomere long arm that was constituted by an inverted
      duplicated 15q24.3-qter segment. Therefore, the resulting add(15)(q) harbored an
      intrachromosomal triplication with the middle segment being inverted in
      orientation. A minor cell lineage (7%) showed an abnormal chromosome 3 resulting
      from a telomeric fusion between its short arm and an inverted duplicated 15q24.3
      qter segment. The third cell lineage (25%) showed a normal 46,XY constitution.
      Finally, this resulted in tetrasomy for the distal 15q24.3-qter region in 75% of
      the patient's lymphocytes. To our knowledge, distal 15q tetrasomy is rare and
      only eight cases have been reported in the literature, all due to a supernumerary
      analphoid marker consisting of an inverted duplication. We report here the first
      observation of distal 15q tetrasomy associated with a 46 chromosomes
      constitution. We compare the phenotype of our patient to previous cases of distal
      tetrasomy 15q and discuss the mechanisms underlying this chromosomal
      rearrangement.

PMID- 15940679
TI  - Maladaptive behaviors and risk factors among the genetic subtypes of Prader-Willi
      syndrome.
AB  - Maladaptive behaviors among 65 people with Prader-Willi syndrome were assessed
      using the Reiss Screen for maladaptive behaviors. Young adults in their twenties
      were more likely to display aggressive behavior than adolescents and older
      adults. Differences in maladaptive behaviors between the typical deletion and
      uniparental disomy (UPD) subtypes were evaluated. The typical deletion subtype
      had higher self-injury and stealing scores than the UPD subtype. Subject
      characteristics were differentially related to maladaptive behavior among the
      typical deletion and UPD subtypes. Differences in maladaptive behavior were also
      examined between the typical deletion type I and type II subtypes. The type I
      deletion subtype had greater physical depression scores than the type II deletion
      subtype. The Reiss Screen cut-off scores were used to determine whether
      differences occurred between the subtypes at a clinically significant level.
      These findings offer insight into the health care needs of people with PWS.

PMID- 15940680
TI  - Mitochondrial alterations and autofluorescent conversion of Candida albicans
      induced by histatins.
AB  - The mechanism of the candidacidal activity of histatins 3 and 5 (Hst) is still a
      matter of debate. Previous studies have indicated that Hst induce cell
      permeabilization, generation of reactive oxygen species (ROS) by mitochondria,
      inhibition of the respiratory chain, and energy-dependent cytotoxic release of
      ATP. On the other hand, the multiplicity of effects and the apparent contrast
      between experimental data continue to render the mechanism of Hst-induced killing
      of C. albicans unclear. In this investigation, using fluorescent probes (the
      potential-sensitive mitochondrial probe tetramethylrhodamine methyl ester
      perchlorate, TMRM; the ROS-sensitive probe dihydrofluorescein diacetate, DHF; the
      membrane-impermeant probe, calcein) and autofluorescence data we observed that
      Hst induce ROS generation by mitochondria undergoing a high energy swelling
      condition, accompanied by oxidation of cytosolic NAD(P)H and mitochondrial
      flavoproteins. ROS generation and swelling, attributable to an inhibition of the
      respiratory chain and to impairment of the K/H-exchanger, were followed by
      mitochondrial depolarization. Mitochondrial changes were accompanied by massive
      calcein influx, indicative of cell permeabilization, and prominent alterations of
      the cell size, shape, and optical density. The loss of proliferative activity was
      correlated, on a single cell basis, to the acquisition of a lipofuscin-like
      autofluorescence.

PMID- 15940681
TI  - The revolution of counting "tops": two decades of the disector principle in
      morphological research.
AB  - Twenty years have passed since the publication of the seminal paper enunciating
      the disector principle by an author using the pseudonym D.C. Sterio. During this
      time, methods based on the revolutionary principle of counting "tops" have become
      progressively better known and have been included in several commercially
      available systems for quantitative morphology. Analysis of the number of
      published studies citing Sterio's paper on the ISI Web of Knowledge database
      showed that its scientific "impact factor" has almost continuously risen since
      its publication, indicating the growing knowledge about disector-based methods in
      the various scientific fields where morphological quantification is required.
      This report briefly reviews the first two decades of disector use, pointing to
      its advantages as well as to shortcomings that have recently been addressed in
      critical papers and have given rise to a lively debate on the role of counting
      tops in quantitative morphology today.

PMID- 15940682
TI  - Cadmium distribution and effects on ultrastructureand chlorophyll status in
      photobionts and mycobionts of Xanthoria parietina.
AB  - In this work, we tried to go deeper inside distribution and toxicity of cadmium
      (Cd) in the macrolichen Xanthoria parietina (L.) Th. Fr. Thalli of this species
      were treated with 0 (control), 4.5, 9, 18, or 36 muM Cd for 24 or 48 hours.
      Transmission electron microscopy, X-ray microanalysis, and electron energy loss
      spectroscopy were exploited to study distribution and ultrastructural effects of
      Cd in thalli; spectrophotometric techniques were utilized for measuring Cd
      effects on chlorophyll (Chl) content; light fluorescence microscopy was used to
      evaluate Chl autofluorescence. The highest Cd concentration caused
      ultrastructural alterations both in the mycobiont and in the photobiont, more
      severe in the latter, decreased total Chl content and progressively quenched Chl
      autofluorescence. Cell wall immobilization was observed in both bionts, and
      evidence pointing to a Cd-binding ability by the concentric bodies in the
      mycobiont was also obtained. Lower Cd concentrations led to slight or even no
      effects on thallus structures and on Chl content and autofluorescence. The
      results obtained suggest that: (1) among the two bionts, the algal partner
      appears to be more susceptible to Cd stress, probably because of the presence of
      delicate and sensitive components such as the chloroplast and photosynthetic
      pigments; (2) a concentration threshold exists for the occurrence of evident
      structural and functional damage in X. parietina thalli exposed to Cd.

PMID- 15940683
TI  - Elemental changes in the brain, muscle, and gut cells of the housefly, Musca
      domestica, exposed to heavy metals.
AB  - The toxic effects of heavy metals on organisms are well established. However,
      their specific action at the cellular level in different tissues is mostly
      unknown. We have used the housefly, Musca domestica, as a model organism to study
      the toxicity of four heavy metals: copper (Cu), zinc (Zn), cadmium (Cd), and lead
      (Pb). These have been fed to larvae at low and high, semi-lethal concentrations,
      and their accumulation in the head, thorax, and abdomen was subsequently measured
      in adult flies. In addition, their impact on the cellular concentration of
      several elements important for cell metabolism-sodium (Na+), magnesium (Mg++),
      phosphorous (P), sulphur (S), chloride (Cl-) and potassium (K+)-were measured in
      neural cells, muscle fibers, and midgut epithelial cells. Our study showed that
      the heavy metals accumulate mainly in the abdomen, in which the concentrations of
      two of the xenobiotic metals, Cd and Pb, were 213 and 23 times more concentrated,
      respectively, than in controls. All the heavy metals affected the cellular
      concentration of light elements in all cell types, but the changes observed were
      dependent on tissue type and were specific for each heavy metal, and its
      concentration.

PMID- 15940684
TI  - Preparation of cells cultured on silicon wafers for mass spectrometry analysis.
AB  - The distribution of specific atoms and molecules within living cells is of high
      interest in bio-medical research. Laser secondary neutral mass spectrometry
      (laser-SNMS) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) detect
      atoms with high sensitivity and spatial resolution. The application of these
      methods to cultured cells requires special preparation techniques preserving
      morphological and chemical integrity of the living cells. The cells should,
      therefore, be grown on a conducting material preventing charging of the sample
      during ion bombardment. Silicon is currently used as the preferred support
      material for non-biological samples in mass spectrometry. This study investigates
      (1) the influence of silicon surfaces on cell growth and (2) the suitability of a
      sandwiched, rapid freezing method to analyse transmembrane ion gradients. Human
      melanoma cells were grown on silicon with polished or etched surfaces. Growth
      kinetics were studied using the Sulforhodamine-B assay. Number, shape, and
      morphology of the cells were assessed by epifluorescence microscopy of calcein AM
      and DAPI-stained cells. Cells were subjected to rapid freezing, freeze
      fracturing, and freeze-drying prior to analysis by TOF-SIMS and laser-SNMS. While
      cell numbers and morphology on the rough silicon wafers were impaired, morphology
      and growth kinetics of cells on polished silicon were identical to control cells
      on cell culture tested polystyrene. TOF-SIMS and laser-SNMS resulted in high
      resolution elemental images and mass spectra. Measurement of the intracellular
      Na+ and K+ concentrations revealed a ratio as observed in living cells. In
      conclusion, culturing cells on polished silicon wafers followed by sandwiched,
      rapid freezing is an adequate preparation method to study intracellular ion
      distribution with mass spectrometry.

PMID- 15940685
TI  - Perovskites in the comb roof base of hornets: their possible function.
AB  - On the ceiling of the Oriental hornet comb cell, there are mineral granules of
      polycrystalline material known to belong to the group of perovskites. In a comb
      cell intended to house a worker hornet, the roof base usually carries one or
      several such perovskite granules containing titanium (Ti), whereas in the roof
      base of a cell housing a developing queen, there are usually several granules
      containing a high percentage of silicon (Si), aluminum (Al), calcium (Ca), and
      iron (Fe), but very little if any Ti. In worker comb cells, Ti usually appears as
      ilmenite (FeTiO3). Besides documenting the above-mentioned facts, this report
      discusses possible reasons for the appearance of ilmenite crystals in worker
      cells only and not in queen cells.

PMID- 15940686
TI  - Prenatal death in Smith-Lemli-Opitz/RSH syndrome.

PMID- 15940687
TI  - Prenatal diagnosis of chromosome 4 mosaicism: prognostic role of cytogenetic,
      molecular, and ultrasound/MRI characterization.
AB  - Trisomy 4 mosaicism is extremely rare: herein we report the cytogenetic and
      molecular characterization and prenatal US findings of a case diagnosed
      prenatally. The diagnosis of level III mosaicism was established in cultured
      amniotic fluid cells (22.5%). At 22 weeks gestation, micrognathia and
      hypotelorism were suspected at 2-D sonography, and confirmed at 3-D examination.
      In addition, 2-D US showed cerebellar hypoplasia associated with borderline
      ventriculomegaly (confirmed at magnetic resonance imaging, MRI), spine deformity
      (hemivertebra), and a complete atrioventricular septal defect (AVSD). The
      pregnancy was terminated. Trisomy 4 mosaicism was confirmed in placental and
      fetal skin cultured cells. The cord blood karyotype was normal. Molecular
      analysis excluded uniparental disomy of chromosome 4, and indicated that the
      trisomy 4 was of maternal meiotic origin. In presence of chromosome 4 mosaicism,
      accurate fetal sonography and echocardiography are mandatory. Low level mosaicism
      and normal echographic examinations seem to be associated with good prognosis. In
      postnatal life, chromosome 4 mosaicism should be suspected, and cytogenetic
      analysis proposed of further tissues (i.e., skin), in presence of craniofacial
      dysmorphism, cardiac defects, and abnormal hands/feet, even if mental development
      is appropriate or only slightly impaired.

PMID- 15940688
TI  - Development of an audit tool for genetic services.
AB  - Rapid growth in demand and altered professional roles have produced changes in
      the delivery of genetic services over the past decade, but these have not been
      rigorously evaluated because of the paucity of appropriate audit tools. The aim
      of this study was to use clients' accounts and factor analysis to develop a
      robust assessment and audit tool. Qualitative data abstracted from several
      published studies were used to generate a number of statements related to
      outcomes of genetic services. A total of 57 statements were incorporated into a
      questionnaire. The questionnaire was mailed to clients of the Wales genetic
      service (n = 133) who had completed their episode of care. Respondents were asked
      to rank each statement on a seven-point Likert type scale. Responses were
      subjected to factor analysis. A total of 97 anonymized responses were received
      (73% response rate). Six main factors were found to contribute to the outcome of
      the service from the client's perspective. These were labeled (i) enhanced
      understanding, (ii) positive psychological change, (iii) respect for autonomy,
      (iv) adaptation, (v) disequilibirium, and (vi) value of contact. The audit tool
      has now been refined for use in evaluating genetic services. Questions are
      included to investigate the six outcome areas shown to be relevant from the
      client's perspective. Data from the next phase of the study will be analyzed to
      validate the tool for use in both clinical audit and research contexts.

PMID- 15940689
TI  - GFP as a tool for the analysis of proteins in the flagellar basal apparatus of
      Chlamydomonas.
AB  - Green fluorescent protein (GFP) was used to analyse three proteins in the
      flagellar basal apparatus of C. reinhardtii: (1) Striated fiber assemblin (SFA),
      the major component of the striated microtubule-associated fibers; (2) Centrin,
      present in the nucleus basal body connectors (NBBCs) and the distal connecting
      fiber (dCF) between the two basal bodies; and (3) DIP13, the Chlamydomonas
      homologue of human autoantigen NA14. The fusions co-localized with the wild-type
      proteins when expressed moderately. Overexpression of centrin-GFP and DIP13-GFP
      resulted in the formation of large aggregates and disturbed the distribution of
      the respective wild-type proteins. The amount of wild-type DIP13 was
      significantly reduced in cells overexpressing DIP13-GFP. Moreover, the cells
      frequently failed to assemble full-length flagella and flagellar regeneration was
      delayed, indicating a role of DIP13 during flagellar assembly. In contrast,
      overexpression of GFP-SFA, which retained more wild-type properties than SFA-GFP,
      increased the size of the striated fibers without altering the cross-shaped
      pattern. Abnormal patterns were observed in centrin-deficient cells, suggesting
      that centrin is required for proper localization of SFA. Photobleaching of GFP
      SFA fibers indicated that GFP-SFA in the fibers is turned over slowly.
      Conditionally expressed centrin-GFP was incorporated into NBBCs in regions close
      to the basal bodies, but underrepresented in the dCF, indicative of a different
      dynamic of these two centrin fibers. Bending of the NBBCs was observed in vivo
      during flagellar motion, indicating that the filaments are flexible. In
      conclusion, in Chlamydomonas GFP-tagging is a useful tool for yielding new
      insights into the function and properties of the analyzed proteins.

PMID- 15940690
TI  - Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle.
AB  - A link between the cardioprotective benefits of pharmacological preconditioning
      and natural mammalian hibernation is considered to involve the cellular
      activation of opioid receptors and subsequent opening of K(ATP) channels. In
      previous studies, we have demonstrated the protective effects of specific delta
      opioid agonists against porcine cardiac ischemia/reperfusion injury. We
      hypothesize here that preincubation with hibernation induction trigger (HIT)
      should confer a similar protection in skeletal muscles. Therefore, muscle bundles
      from swine were pretreated with plasma from hibernating woodchucks (HWP) for 30
      min, then exposed to hypoxia for 90 min and reoxygenation for 120 min. Stimulated
      twitch forces were assessed. The functional effects of pretreatment with
      nonhibernation (summer) woodchuck plasma, a K(ATP) blocker, or opioid antagonist
      were also studied. During the reoxygenation period, significantly greater force
      recoveries were observed only for bundles pretreated with HWP; this response was
      blocked by naloxone (P < 0.05). We conclude that HIT pretreatment could be used
      to confer protection against hypoxia/reperfusion injury of skeletal muscles of
      nonhibernators; it could potentially be utilized to prevent injury during
      surgical procedures requiring ischemia.

PMID- 15940691
TI  - Identification of consistent novel submegabase deletions in low-grade
      oligodendrogliomas using array-based comparative genomic hybridization.
AB  - We have analyzed 18 low-grade gliomas using array comparative genomic
      hybridization (aCGH) with an average resolution of <500 kb. Because the majority
      of these tumors showed loss of chromosome arms 1p and 19q, we used custom
      statistical approaches to define submegabase hemizygous losses throughout the
      genome that correlated with 19q loss. As a result of this analysis, we have
      identified a approximately 550-kb region in 11q13 and a approximately 300-kb
      region in 13q12 that showed hemizygous deletion in virtually all the tumors
      analyzed regardless of their 1p/19q status. FISH analyses of interphase nuclei
      from the same tumors used for aCGH analysis confirmed the hemizygous loss. The
      identification of such specific changes provides a potentially very useful
      diagnostic marker for this subgroup of low-grade tumors. These regions of the
      genome define small numbers of candidate genes that are within the deletions. The
      aCGH analysis also defined the spectrum of gain and loss of genomic regions in
      low-grade oligodendrogliomas.

PMID- 15940692
TI  - Interstitial telomeric DNA sequences of Chinese hamster cells are hypersensitive
      to nitric oxide damage, and DNA-PKcs has a specific local role in its repair.
AB  - The DNA breakage detection-fluorescence in situ hybridization (DBD-FISH)
      procedure was used to analyze DNA single-strand breaks (SSBs) and alkali-labile
      sites induced by exposure to the nitric oxide (NO) donors sodium nitroprusside
      (SNP) and 3-morpholinosydnomine hydrochloride (SIN-1) in the whole genome and in
      long interstitial telomeric repeat sequence (ITRS) blocks from Chinese hamster
      cells. The relative density of DNA damage generated in the ITRS by X-rays was
      similar to that induced in the genome overall, whereas it was 1.7 times higher
      when the alkylating agent MNNG was assayed. Nevertheless, after SNP or SIN-1
      treatment, ITRSs proved to be 2.8 and 2.7 times relatively more damaged,
      respectively, than the whole genome. When the DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs) was not active, as in XR-C1 mutant cells, the repair
      kinetics in the whole genome did not differ from that in the parental cell line
      with X-ray or SNP exposure. However, whereas the SSBs and alkali-labile sites
      induced in the ITRS by X-rays exhibited rejoining kinetics similar to that of the
      parental cell line, the damage induced by SNP was more slowly rejoined. This
      implies a role for DNA-PKcs in the repair of DNA damage induced by NO, especially
      in ITRSs. The results demonstrated intragenomic heterogeneity of NO-induced DNA
      damage and repair; there was a higher density of DNA damage in the ITRS blocks,
      possibly because of their guanine richness. This suggests that a parallel process
      may occur in the terminal telomeres, which has implications for premature aging
      and neoplastic development by chronic NO exposure in vivo.

PMID- 15940693
TI  - PTPN11 mutations play a minor role in isolated congenital heart disease.
AB  - PTPN11 missense mutations cause approximately 50% of Noonan syndrome, an
      autosomal dominant disorder presenting with various congenital heart defects,
      most commonly valvar pulmonary stenosis, and hypertrophic cardiomyopathy.
      Atrioventricular septal defects and coarctation of the aorta occur in 15% and 9%,
      respectively. The aim of this study was to determine if PTPN11 mutations exist in
      non-syndromic patients with these two relevant forms of congenital heart disease.
      The 15 coding PTPN11 exons and their intron boundaries from subjects with
      atrioventricular septal defects (n = 24) and coarctation of the aorta (n = 157)
      were analyzed using denaturing high performance liquid chromatography and
      sequenced if abnormal. One subject with an atrioventricular septal defect but no
      other known medical problems had a c.127C > T transition in exon 2, predicting a
      p.L43F substitution. This mutation affected the phosphotyrosine-binding region in
      the N-terminal src homology 2 domain and was close to a Noonan syndrome mutation
      (p.T42A). An otherwise healthy patient with aortic coarctation had a silent
      c.540C > T change in exon 5 corresponding to p.D180D. Our study showed that
      PTPN11 mutations are rarely found in two isolated forms of congenital heart
      disease that commonly occur in Noonan syndrome. The p.L43F mutation belongs to a
      rare class of PTPN11 mutations altering the phosphotyrosine-binding region. These
      mutations are not predicted to alter the autoinhibition of the PTPN11 protein
      product, SHP-2, which is the mechanism for the vast majority of mutations causing
      Noonan syndrome. Future studies will be directed towards understanding these rare
      phosphotyrosine binding region mutants.

PMID- 15940694
TI  - Detection of genomic rearrangements by DHPLC: a prospective study of 90 patients
      with inherited peripheral neuropathies associated with 17p11.2 rearrangements.
AB  - Large genomic duplications and deletions are increasingly recognized as a cause
      of human disease. Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy
      with liability to pressure palsy (HNPP) result, respectively, from a duplication
      or deletion of a 1.5 Mb genomic region in 17p11.2-12, containing the PMP22 gene.
      In routine diagnostic analysis, CMT1A status is inferred from the detection of an
      imbalanced dosage of two alleles or the presence of three alleles of a
      polymorphic marker flanking the PMP22 gene. HNPP is suspected if only one allele
      is seen, but hemizygosity must be confirmed by analyzing allele segregation in
      the family or by other techniques such as Southern blotting or fluorescence in
      situ hybridization (FISH). PCR-based methodologies have also been developed that
      allow single-step determination of the PMP22 gene copy number, wherein amplicons
      are typically labeled and/or separated by gel electrophoresis. We describe here a
      fast and reliable PCR-based method for the diagnosis of CMT1A and HNPP in which
      the PMP22 gene is co-amplified with a reference gene, and the amplicons are
      separated according to their size and quantified by DHPLC. Our results suggest
      that this method for quantifying gene dosage could be applied to other genomic
      rearrangements.

PMID- 15940695
TI  - A novel filamin A D203Y mutation in a female patient with otopalatodigital type 1
      syndrome and extremely skewed X chromosome inactivation.
AB  - Otopalatodigital syndrome type 1 (OPD1) [OMIM 311300] is an X-linked dominant
      multiple congenital anomalies disease mainly characterized by a generalized
      skeletal dysplasia, mild mental retardation, hearing loss, cleft palate, and
      typical facial anomalies. OPD1 belongs to a group of X-linked skeletal dysplasias
      known as oto-palato-digital syndrome spectrum disorders that also include OPD2,
      Melnick-Needles syndrome (MNS), and frontometaphyseal dysplasia (FMD). Recently,
      it has been demonstrated that mutations in the gene encoding the cytoskeletal
      protein Filamin A (FLNA) are responsible for this group of clinically overlapping
      human syndromes. We present the phenotypic and molecular data of a sporadic
      female patient clinically diagnosed with an OPD1 syndrome who carried a novel
      FLNA point mutation resulting in an Asp203Tyr substitution in the actin-binding
      domain of the protein. X-inactivation analyses demonstrated an extremely skewed
      pattern towards her maternal chromosome. Our results add to the molecular
      spectrum of the oto-palato-digital related syndromes and contribute to the
      delineation of phenotype-genotype correlation in this group of X-linked skeletal
      disorders.

PMID- 15940696
TI  - Cerebellar vermis aplasia: patient report and exclusion of the candidate genes
      EN2 and ZIC1.
AB  - Cerebellar vermis aplasia (ACV, OMIM 117360) is a rare malformation of the
      cerebellum, with only few familial patients reported so far. Main clinical
      features of this rare disorder include floppiness and delayed milestones in early
      infancy, preceding mild cerebellar ataxia, non-progressive clinical course,
      normal or slightly delayed intelligence, and occasional nystagmus. Neuroimaging
      reveals selective involvement of the cerebellum, which is prominent in the
      vermis. Because of the large preponderance of female patients, X-linked dominant
      transmission was suggested by [Fenichel and Phillips (1989); Arch Neurol 46:582
      583], and subsequent reports only concern female patients. Only one family with
      male-to-male transmission presenting with a generalized atrophy of the cerebellum
      rather than a more localized vermis aplasia has been reported so far. We report
      on a family in which father and son are affected by a mild form of ACV, thus
      confirming an autosomal mode of inheritance of the disease. Our patients showed a
      progressive improvement of their motor abilities, neurological examination of the
      father being actually normal except for a mild mental retardation. We also
      evaluated the potential role of two candidate genes, EN2 and ZIC1, responsible
      for abnormal cerebellar development in murine knock-out models. However,
      molecular analysis failed to reveal any causative mutation in the coding sequence
      of the two genes in our patients. The understanding of the genetic basis of
      autosomal dominant ACV would allow a better classification of isolate cerebellar
      malformations and might permit to understand cell differentiation and migration
      in the developing central nervous system.

PMID- 15940697
TI  - Generalized arterial calcification of infancy: different clinical courses in two
      affected siblings.
AB  - Generalized arterial calcification of infancy (GACI) is a rare autosomal
      recessive disease caused by mutations in ENPP1. Due to extensive calcification of
      the arterial media associated with intimal proliferation leading to vascular
      occlusion, most affected children die within the first 6 months of life. We
      report on two Taiwanese siblings with an identical genotype, but different
      clinical course. The male sibling developed heart failure and severe
      hypertension, and died at the age of 6 weeks despite of treatment with
      bisphosphonates, ACE inhibitors, and hydralazine. The subsequent female, who was
      monitored closely pre- and post-natally, is having an uncomplicated clinical
      course up to the age of 1(1/2) year now. There were similar characteristic
      sonographic and roentgenographic findings in both siblings in early infancy. In
      both siblings, the same compound heterozygous mutations (c.1025G > T
      [p.Gly342Val] and c.1112A > T [Tyr371Phe]) in ENPP1 were identified. Despite the
      same genotype and similar sonographic and radiographic features in early infancy,
      the phenotype of GACI can vary to a great extent within one family.

PMID- 15940698
TI  - Risks for severe mental retardation occurring in isolation and with other
      developmental disabilities.
AB  - Individual and maternal characteristics as potential risk factors for having
      severe mental retardation (SMR) occurring with and without cerebral palsy (CP),
      epilepsy, or a pervasive developmental disorder (PDD) were explored among a
      cohort of 119,404 children without Down syndrome born in the California Central
      Valley in 1992 and 1993. Unadjusted and adjusted relative risks (RRs) and their
      95% confidence intervals (CIs) based on the Poisson distribution were used to
      estimate the risks associated with each individual and maternal factor studied
      for each SMR diagnostic category. The most notable increased risks for SMR
      occurring in isolation or with CP or epilepsy was for children born low-birth
      weight or preterm who were at a substantially increased risk (RRs 2.6-9.9). In
      contrast, the risk of SMR occurring with a PDD was the greatest among males
      compared to females (RR = 3.4, 95% CI 1.5, 7.9), Blacks compared to Whites (RR =
      5.1, 95% CI 1.7, 15.5), and Asians compared to Whites (RR = 3.9, 95% CI 1.3,
      12.0). Etiologic heterogeneity when SMR occurs with a PDD was suggested.

PMID- 15940699
TI  - Update: PGD and Holt-Oram syndrome.

PMID- 15940700
TI  - Hair whorls and handedness: informative phenotypic markers in nonsyndromic cleft
      lip with or without cleft palate (NS CL/P) cases and their unaffected relatives.
AB  - Cleft lip with or without cleft palate (CL/P) is a complex disorder with a range
      of phenotypic manifestations and a birth prevalence that varies by population
      (1/500-1/2,000). Investigators have postulated that CL/P cases may have abnormal
      brain development, citing structural brain differences, and cognitive impairments
      in affected individuals. Previously, increased levels of non-right handedness
      (NRH), a marker for abnormal brain lateralization, have also been demonstrated in
      CL/P cases. Atypical hair whorls, more direct markers of altered brain
      development, may be related to NRH. To date, neither hair whorl patterns nor
      their relationship to NRH have been studied in a CL/P population. In the current
      study, we investigate the hypothesis that altered brain development is part of
      the phenotypic spectrum of NS CL/P by assessing NRH and atypical hair whorls in
      CL/P families. The study population included 49 nonsyndromic CL/P cases and 116
      of their unaffected relatives; 21.8% of the study population was NRH compared to
      the 10% population estimate (P < 0.0001). Counter-clockwise hair whorls (CCW)
      were found in 12.7% of all subjects compared to a population rate of 9.9 %. Of
      all subjects, 11% of the NRH individuals had CCW, which was similar to the
      frequency of CCW in right-handed individuals. Approximately 80% of the whorls
      were placed on either the right or center of the scalp. No significant
      associations were found between the type of cleft and handedness, hair whorl
      rotation, or placement. These results suggest that certain phenotypic markers of
      abnormal brain development may comprise part of the extended phenotype of
      orofacial clefting.

PMID- 15940701
TI  - Mosaicism for an FMR1 gene deletion in a fragile X female.
AB  - Most cases of fragile X syndrome result from expansion of CGG repeats in the FMR1
      gene; deletions and point mutations of FMR1 are much less common. Mosaicism for
      an FMR1 full mutation with a deletion or with a normal allele has been reported
      in fragile X males. Here we report on a fragile X female who is mosaic for an
      FMR1 full mutation and an intragenic deletion. The patient is a 4-year-old girl
      with developmental delay, autistic-like behaviors, and significant speech and
      language abnormalities. Southern blotting demonstrated the presence of a
      methylated full mutation, a normal allele in methylated and unmethylated forms,
      and an additional fragment smaller than the normal methylated allele. This result
      indicates that the patient is mosaic for a full mutation and a deletion, in the
      presence of a normal allele. By DNA sequence analysis, we mapped the 5'
      breakpoint 63/65 bp upstream from the CGG repeat region and the 3' breakpoint
      86/88 bp downstream of the CGG repeats within the FMR1 gene. The deletion removed
      210 bp, including the entire CGG repeat region. The full mutation was inherited
      from a premutation in the patient's mother. The deletion, which remained
      methylated at the Eag I and Nru I sites, was probably derived from the full
      mutation allele. Mosaicism of this type is rare in females with a fragile X
      mutation but should be kept in mind in the interpretation of Southern blots.

PMID- 15940702
TI  - Terminal deletion of 6p results in a recognizable phenotype.
AB  - With improved cytogenetic techniques, small deletions and duplications are being
      identified with increased frequency. We report four cases with terminal deletions
      involving the 6p24- and 6p25-pter chromosomal segment who exhibit a distinct,
      recognizable pattern of malformations including hypertelorism, downslanting
      palpebral fissures, flat nasal bridge, Dandy-Walker malformation/variant,
      congenital heart defects, anterior eye-chamber abnormalities, hearing loss, and
      developmental delay. We also compare the clinical aspects of these patients to
      those of previously reported cases in the literature with similar terminal
      deletions of chromosome 6p. Routine chromosome analysis can miss this deletion,
      therefore, high-resolution chromosome analysis is indicated for individuals who
      exhibit these distinct features. Furthermore, individuals with this deletion
      should have an ophthalmologic exam, cardiac evaluation, head imaging, renal
      ultrasound, and formal hearing evaluation.

PMID- 15940703
TI  - The adult phenotype in Costello syndrome.
AB  - We report clinical findings in 17 adults with Costello syndrome ranging in age
      from 16 to 40 years. Two patients in this series have had bladder carcinoma, the
      only malignancy reported to affect adults with Costello syndrome. Benign tumors
      included multiple ductal papillomata in two women, and a fourth ventricle mass in
      one man, thought to be a choroid plexus papilloma. Endocrine problems in this
      series were osteoporosis, central hypogonadism, and delayed puberty. Other health
      problems were symptomatic Chiari malformations in three patients. Four patients
      had adult-onset gastro-esophageal reflux, three of whom had Chiari malformations.
      Fourteen adults had mild to moderate intellectual disability with three
      individuals having severe intellectual disability; 15 individuals attained some
      reading and writing skills and 14 showed ongoing acquisition of new skills into
      adulthood. On the basis of this data, we recommend that neuro-imaging be
      considered in adults with Costello syndrome if they develop symptoms suggestive
      of a Chiari malformation. In the event of pubertal delay, endocrine
      investigations are indicated and hormone treatment may be required. Bone density
      assessments should be performed in adults with Costello syndrome, particularly in
      those with pubertal abnormalities. Screening for microscopic hematuria as a
      marker for bladder carcinoma may be indicated, although this requires further
      evaluation.

PMID- 15940704
TI  - Direct analysis of unphased SNP genotype data in population-based association
      studies via Bayesian partition modelling of haplotypes.
AB  - We describe a novel method for assessing the strength of disease association with
      single nucleotide polymorphisms (SNPs) in a candidate gene or small candidate
      region, and for estimating the corresponding haplotype relative risks of disease,
      using unphased genotype data directly. We begin by estimating the relative
      frequencies of haplotypes consistent with observed SNP genotypes. Under the
      Bayesian partition model, we specify cluster centres from this set of consistent
      SNP haplotypes. The remaining haplotypes are then assigned to the cluster with
      the "nearest" centre, where distance is defined in terms of SNP allele matches.
      Within a logistic regression modelling framework, each haplotype within a cluster
      is assigned the same disease risk, reducing the number of parameters required.
      Uncertainty in phase assignment is addressed by considering all possible
      haplotype configurations consistent with each unphased genotype, weighted in the
      logistic regression likelihood by their probabilities, calculated according to
      the estimated relative haplotype frequencies. We develop a Markov chain Monte
      Carlo algorithm to sample over the space of haplotype clusters and corresponding
      disease risks, allowing for covariates that might include environmental risk
      factors or polygenic effects. Application of the algorithm to SNP genotype data
      in an 890-kb region flanking the CYP2D6 gene illustrates that we can identify
      clusters of haplotypes with similar risk of poor drug metaboliser (PDM)
      phenotype, and can distinguish PDM cases carrying different high-risk variants.
      Further, the results of a detailed simulation study suggest that we can identify
      positive evidence of association for moderate relative disease risks with a
      sample of 1,000 cases and 1,000 controls.

PMID- 15940705
TI  - Identification of Helicobacter sp. in gastric mucosa from captive marmosets
      (Callithrix sp.; callitrichidae, primates).
AB  - The aim of this study was to identify the presence of Helicobacter sp. in the
      gastric mucosa of captive marmosets (Callithrix sp.). Histologic specimens from
      the fundic, corpus, and antral gastric regions of six Callithrix jacchus, 12 C.
      kuhli, and 12 C. geoffroyi specimens were evaluated. The sections were stained
      with hematoxylin-eosin (H&E) and the Warthin-Starry silver impregnation method,
      and immunostained with rabbit anti-H. pylori polyclonal antibody. Helicobacter
      like organisms (HLOs) and coccoid forms were present in silver-stained sections
      from 29 stomachs, whereas immunohistochemistry (IHC) tests revealed bacterial
      aggregates in 15 stomachs. No statistical difference relative to the presence of
      Helicobacter sp. was found among the gastric regions or marmoset species. Gastric
      lesions were found in the groups of marmosets that had positive and negative IHC
      results, but no correlation between inflammation and Helicobacter sp. infection
      was established. These findings demonstrate that marmosets are susceptible to
      naturally-occurring Helicobacter sp. infection, and open the way to the
      development of comparative studies on Helicobacter sp. infection in humans.

PMID- 15940706
TI  - Neighbor effect: evidence of affiliative and agonistic social contagion in
      captive chimpanzees (Pan troglodytes).
AB  - Previous studies of captive chimpanzees have demonstrated the "neighbor effect,"
      or social contagion, with respect to agonistic vocalizations and behaviors. The
      present study considers whether there is a relationship between behavior patterns
      in focal animals and the auditory signals of neighboring social groups. Using
      focal-group sampling, we collected 172.5 hr of data on 51 subjects (25 females
      and 26 males) housed in 10 social groups. We performed two-tailed Wilcoxon
      matched-pairs signed-rank tests to determine whether the relative frequency of
      the vocalizations (high vs. low) affected the behaviors. In keeping with past
      research, we found that agonistic noises and vocalizations from neighboring
      social groups had a significant effect on the rates of focal-group bluff
      displays, pant-hoots, and aggression (P<0.05). In addition, we also found
      significant relationships between grooming behavior and vocalizations in focal
      groups, and grooming vocalizations from neighboring groups (P<0.05). The results
      suggest that social contagion is not limited to aggressive behaviors, but also
      occurs for affiliative behavior patterns.

PMID- 15940707
TI  - Proximity and estrous synchrony in Mahale chimpanzees.
AB  - Since McClintock [Nature 229:244-255, 1971] first reported menstrual synchrony in
      women, a number of studies have reported similar phenomena. Many researchers have
      suggested that one of the proximate factors leading to synchrony is spatial
      proximity among females (e.g., close friends or roommates). However, most studies
      on menstrual synchrony have been conducted in limited spaces, and it remains to
      be determined whether controlled environments, such as those used in experiments,
      actually exist in the wild. In this study, we analyzed the relationship between
      proximity and estrous synchrony using data from wild female chimpanzees at
      Mahale, Tanzania. In the cycling females, we observed two pairs that spent a
      large amount of time together. We compared the estrous synchrony indices (ESIs)
      between these two pairs and the other females. Our results showed that the ESIs
      of the high-proximity pairs did not differ from those of other pairs. .

PMID- 15940708
TI  - Galago locomotion in Kibale National Park, Uganda.
AB  - Very few locomotor studies have been conducted on galagos. This is surprising
      given their interesting anatomy and ecology, as well as their increasing species
      diversity. In this study we investigated locomotion and postures in two sympatric
      galagos species (Galagoides thomasi and Galago matschiei) living in Kibale
      National Park, Uganda. G. thomasi uses arboreal quadrupedalism and leaping, while
      G. matschiei is more leaping-oriented. Both species utilize small oblique
      branches in the mid-canopy. These similarities in substrate use are most likely
      due to the similar body sizes and anatomies of the two species, as well as to the
      structure and availability of trees in Kibale National Park. Lastly, we compare
      the locomotor patterns of G. thomasi and G. matschiei with those observed in the
      few other quantitative locomotor studies available for galagos.

PMID- 15940709
TI  - Sex differences in scent marking in Propithecus edwardsi of Ranomafana National
      Park, Madagascar.
AB  - In this study we compared the scent-marking rates of females with those of males.
      Specifically, we examined the ability of season, dominance status, and natal
      status to explain the frequency of scent marking in female sifakas living wild in
      Ranomafana National Park, Madagascar, and compared the results with those
      published for males [Pochron et al., American Journal of Primatology, in press].
      We also sought to determine whether vulnerability to infanticide affects marking
      frequency in adults of either sex, and whether female reproductive status affects
      female marking behavior. We found that males marked at twice the rate of females,
      and like males, females in single-female groups marked at the highest rates.
      Dominant females and non-natal females marked at higher rates than did
      subordinate females and natal females, a pattern also seen in males. This
      suggests that scent marks may convey important information about status. Neither
      females nor males varied their marking frequency with the presence of vulnerable
      infants. Females did not alter marking frequency with reproductive state, and
      like males, they marked at higher rates in the period prior to the mating season
      than they did in the mating season itself. This implies that females may use
      scent marks more for intrasexual aggression or territoriality than for mate
      attraction.

PMID- 15940710
TI  - Testosterone and energetics in wild chimpanzees (Pan troglodytes schweinfurthii).
AB  - Ovarian function in female hominoids is sensitive to both energy flux and energy
      balance, resulting in a reduced probability of conception during periods when a
      successful reproductive outcome is less likely. However, the extent to which
      energetic factors constrain gonadal function in male hominoids is not clear. We
      examined the effects of both acute and chronic variation in energy availability
      on urinary testosterone (T) levels in adult male chimpanzees. Acute changes in
      energy availability, which were assayed by means of observational data on feeding
      behavior, did not result in decreased T production for 11 individuals at Kibale
      National Park, Uganda. Chronic energy shortages, on the other hand, may be
      associated with lower T levels in this population. Adult males in Kibale (n=11),
      who maintain suboptimal access to energy, exhibit significantly lower urinary T
      levels than males in captivity (n=11), who are more sedentary and better fed.
      These results suggest that data on hormonal function in captive chimpanzees
      should be interpreted with caution because individuals may produce T at levels
      well above those that are typical in the wild. They also suggest that short-term
      variations in T levels in male hominoids are more likely to be explained by
      social factors than by energetic ones.

PMID- 15940711
TI  - Interpopulation differences in exudate feeding of pygmy marmosets in Ecuadorian
      Amazonia.
AB  - Local variations in fruit- and leaf-eating have been reported for some primate
      species; however, similar variations in exudate-feeding of pygmy marmosets, one
      of the most specialized neotropical primate species, have not been studied. In
      our 3-year study of four populations of pygmy marmosets in northeastern Ecuador,
      we characterized their exudate-feeding behavior by describing the use of exudate
      sources. We tested whether the use of exudate species was related to ecological
      factors such as the availability of exudate species in an area. We estimated the
      daily activity budgets of the groups with 1-hr scan samples and found significant
      interpopulation differences in the time spent on exudate feeding. We recorded a
      total of 18 exudate species used in the four populations; however, the
      populations differed in the total number of species used and in the preferred
      species. The most commonly used plant species were Sterculia apetala at San
      Pablo, Cedrela odorata at Sacha, Inga marginata at Amazoonico, and Parkia
      balslevii at Zancudo. We recorded the presence and abundance of the 18 exudate
      species in 90-m transects in the home range of each group and in one additional
      control area that contained no marmosets, for each population. Differences in the
      most-used exudate species among populations did not appear to be related to the
      availability of these species in each population, i.e., the marmosets did not use
      at random the exudate species available within their range, nor did they use more
      often the exudate species that were more abundant in their home ranges. One
      implication of our results for conservation is that protecting exudate resources
      based on data from only one area will not be sufficient to preserve pygmy
      marmosets in all populations.

PMID- 15940712
TI  - Age differences in neophilia, exploration, and innovation in family groups of
      callitrichid monkeys.
AB  - The prevailing assumption in the primate literature is that young or juvenile
      primates are more innovative than adult individuals. This innovative tendency
      among the young is frequently thought to be a consequence, or side effect, of
      their increased rates of exploration and play. Conversely, Reader and Laland's
      [International Journal of Primatology 22:787-806, 2001] review of the primate
      innovation literature noted a greater reported incidence of innovation in adults
      than nonadults, which they interpreted as (in part) a reflection of the greater
      experience and competence of older individuals. Within callitrichids there is
      contradictory evidence for age differences in response to novel objects, foods,
      and foraging tasks. By presenting novel extractive foraging tasks to family
      groups of callitrichid monkeys in zoos, we examined, in a large sample, whether
      there are positive or negative relationships of age with neophilia, exploration,
      and innovation, and whether play or experience most facilitates innovation. The
      results indicate that exploration and innovation (but not neophilia) are
      positively correlated with age, perhaps reflecting adults' greater manipulative
      competence. To the extent that there was evidence for play in younger
      individuals, it did not appear to contribute to innovation. The implications of
      these findings for the fields of innovation and conservation through
      reintroduction are considered.

PMID- 15940713
TI  - Disproportionate participation by age/sex classes in aggressive interactions
      between long-tailed macaques (Macaca fascicularis) and human tourists at
      Padangtegal monkey forest, Bali, Indonesia.
AB  - We observed 420 aggressive interactions between tourists and Macaca fascicularis
      at the Padangtegal Wanara Wana Temple forest site in Bali, Indonesia, during the
      months of June and July 2001. The data collected included patterns of aggression,
      presence or absence of food, and demographic information on resident macaques and
      human visitors. Analyses of the interactions suggest that macaques respond
      differentially to humans according to the age/sex classes involved. Additionally,
      adult and subadult male macaques participated in more aggressive behaviors than
      expected, while adult female macaques and immatures participated in such
      behaviors less than expected. These variations in interaction patterns between
      macaques and tourists may have substantial implications for management issues and
      the potential for pathogen transmission.

PMID- 15940714
TI  - Risk of silicosis in cohorts of Chinese tin and tungsten miners and pottery
      workers (II): Workplace-specific silica particle surface composition.
AB  - BACKGROUND: It is hypothesized that surface occlusion by alumino-silicate affects
      the toxic activity of silica particles in respirable dust. In conjunction with an
      epidemiological investigation of silicosis disease risk in Chinese tin and
      tungsten mine and pottery workplaces, we analyzed respirable silica dusts using a
      multiple-voltage scanning electron microscopy-energy dispersive X-ray
      spectroscopy (MVSEM-EDS). METHODS: Forty-seven samples of respirable sized dust
      were collected on filters from 13 worksites and were analyzed by MVSEM-EDS using
      high (20 keV) and low (5 keV) electron beam accelerating voltages. Changes in the
      silicon-to-aluminum X-ray line intensity ratio between the two voltages are
      compared particle-by-particle with the 90th percentile value of the same
      measurements for a ground glass homogeneous control sample. This provides an
      index that distinguishes a silica particle that is homogeneously aluminum
      contaminated from a clay-coated silica particle. RESULTS: The average sample
      percentages of respirable-sized silica particles alumino-silicate occlusion were:
      45% for potteries, 18% for tin mines, and 13% for tungsten mines. The difference
      between the pottery and the metal mine worksites accounted for one third of an
      overall chi-square statistic for differences in change in measured silicon
      fraction between the samples. CONCLUSION: The companion epidemiological study
      found lower silicosis risk per unit cumulative respirable silica dust exposure
      for pottery workers compared to metal miners. Using these surface analysis
      results resolves differences in risk when exposure is normalized to cumulative
      respirable surface-available silica dust.

PMID- 15940715
TI  - Antithetical effect of tumor necrosis factor-alphagene polymorphism on coal
      workers' pneumoconiosis (CWP).
AB  - BACKGROUND: Inter-individual variation in the severity of pneumoconiosis has been
      described, even with the same environmental exposure. We hypothesized that TNF
      alpha promoter polymorphisms associate with lung responses to environmental
      exposure in coal worker's pneumoconiosis (CWP) patients. METHODS: We examined
      polymorphisms at -238, -308, and -376 in 124 patients with CWP who had similar
      dust exposure history and in 122 non-exposed controls. CWP patients were divided
      into two groups: (1) nodular CWP (n = 84); (2) progressive massive fibrosis (PMF)
      (n = 44). RESULTS: The -308 A allele frequency was higher in patients with CWP
      compared to controls (6.35% and 2.05%, P < 0.01). It was also higher in patients
      with nodular CWP compared to PMF (P < 0.05). Logistic regression analysis
      revealed that patients with the -308 A allele were 3.8 times (P = 0.036) and
      those with smoking habit were 2.3 times (P < 0.002) more likely to have nodular
      CWP than PMF. CONCLUSION: TNF-alpha-308 A allele might interact with smoking to
      enhance susceptibility to nodular CWP.

PMID- 15940716
TI  - Trends in work-related musculoskeletal disorder reports by year, type, and
      industrial sector: a capture-recapture analysis.
AB  - BACKGROUND: Musculoskeletal disorders (MSD) are thought to be declining based on
      Bureau of Labor Statistics survey data, but there is also evidence of MSD under
      reporting, raising the possibility of contrary trends. The magnitude of MSD under
      reporting over time, and its industry distribution have not been adequately
      described. METHODS: Capture-recapture analysis of 7 years of Connecticut MSD
      (1995-2001), utilizing Workers' Compensation and physician reporting data was
      performed. RESULTS: Only 5.5%-7.9% of MSD cases appear to be reported to Workers
      Compensation annually. The capture-recapture estimated average annual rate for
      upper-extremity MSD was 133.1 per 10,000 employed persons, far above BLS rates.
      By industry, Manufacturing, State Government, and the Finance/Insurance/Real
      Estate sectors all had significantly higher MSD rates than Wholesale/Retail
      Trade. CONCLUSIONS: Upper-extremity MSD appears to be significantly under
      reported, and rates are not decreasing over time. Capture-recapture methods
      provide an improved surveillance method for monitoring temporal trends in injury
      rates.

PMID- 15940717
TI  - Work-related eye injuries treated in hospital emergency departments in the US.
AB  - BACKGROUND: Eye injuries account for 3.3% of all occupational injuries resulting
      in lost workdays in private industry in the United States. Work-related eye
      injuries among individuals 15 years of age and older treated in hospital
      emergency departments (EDs) in the United States in 1999 were investigated in
      this study. METHODS: Work-related eye injuries treated in hospital EDs in the US
      were identified from the Work-Related Injury Statistics Query System (Work
      RISQS). National estimates of the numbers and rates per 10,000 full-time worker
      equivalents (FTE) of work-related eye injuries were determined by gender and age.
      The characteristics of these injuries were described, including the injury event,
      the main source of injury, injury diagnosis, and the disposition of the injured
      patient. RESULTS: In 1999, there were approximately 280,000 (95% confidence
      interval (CIs) +/- 66,400) work-related eye injuries treated in hospital EDs,
      with individuals 20-34 years of age at highest risk for work-related eye injury.
      Foreign-bodies in the eye and chemical burns were among the most common types of
      work-related eye injuries. CONCLUSIONS: The findings of this study underscore the
      need for use of appropriate eye protection and implementation, and enforcement of
      eye protection policies in the workplace to prevent work-related eye injuries.

PMID- 15940718
TI  - Risk of silicosis in cohorts of Chinese tin and tungsten miners, and pottery
      workers (I): an epidemiological study.
AB  - BACKGROUND: Epidemiological evaluations of the risk of silicosis in relation to
      exposure to crystalline silica have raised the question of whether different
      types of silica dust exposures vary with respect to their ability to cause
      silicosis. The aim of this study is to compare the risk of silicosis among
      cohorts of silica dust-exposed Chinese tin miners, tungsten miners, and pottery
      workers and to assess whether gravimetric measurements of respirable silica dust
      sufficiently determine the risk of silicosis or whether other factors of exposure
      may play a significant role. METHODS: Cohorts were selected from 20 Chinese mines
      and potteries. Inclusion criteria were starting employment after January 1, 1950
      and being employed for at least 1 year during 1960-1974 in one of the selected
      workplaces. Radiological follow-up for silicosis onset was from January 1, 1950
      through December 31, 1994. Silicosis was assessed according to the Chinese
      radiological criteria for diagnosis of pneumoconiosis (as suspect, Stage I, II,
      or III). Exposure-response relationships were estimated for silicosis of Stage I
      or higher. Silica dust exposure was estimated in terms of cumulative total dust
      exposure, calculated from a workplace, job title, and calendar year exposure
      matrix, and individual occupational histories. Cumulative total dust exposure was
      converted in two steps into cumulative respirable dust exposure and cumulative
      respirable silica dust exposure using conversion factors estimated from side-by
      side measurements conducted in 1988-89. RESULTS: The male cohorts included 4,028
      tin miners, 14,427 tungsten miners, and 4,547 pottery workers who had similar
      onset of employment and duration of follow-up. For a given exposure level, the
      risk of silicosis was higher for the tin and tungsten than the pottery workers.
      CONCLUSION: The observed differences in the risk of silicosis among the three
      cohorts suggest that silica dust characteristics, in addition to cumulative
      respirable silica dust exposure, may affect the risk of silicosis.

PMID- 15940719
TI  - One agent, many diseases: exposure-response data and comparative risks of
      different outcomes following silica exposure.
AB  - BACKGROUND: Evidence in recent years indicates that silica causes lung cancer,
      and probably renal disease, in addition to its well-known relationship to
      silicosis. There is also suggestive evidence that silica can cause arthritis and
      other auto-immune diseases. Silica has, therefore, joined a handful of other
      toxic exposures such as tobacco smoke, dioxin, and asbestos which cause multiple
      serious diseases. METHODS: The available exposure-response data for silica and
      silicosis, lung cancer, and renal disease are reviewed. We compare the
      corresponding excess risks (or absolute risks in the case of silicosis) of death
      or disease incidence by age 75 for these three diseases, subsequent to a lifetime
      (45 years) of exposure to silica at current US standard (0.1 mg/m(3) respirable
      crystalline silica). RESULTS: The absolute risk of silicosis, as defined by small
      opacities greater than or equal to ILO classification 1/1 on an X-ray, ranges
      from 47% to 77% in three cohort studies with adequate follow-up after employment.
      The absolute risk of death from silicosis is estimated at 1.9% (0.8%-2.9%), based
      on a pooled analysis of six cohort studies. The excess risk of lung cancer death,
      assuming US male background rates, is 1.7% (0.2%-3.6%), based on a pooled
      analysis of ten cohort studies. The excess risk of end-stage renal disease
      (assuming male background rates) is 5.1% (2.2%-7.3%), based on a single cohort.
      The excess risk of death from renal disease is estimated to be 1.8% (0.8%-9.7%),
      based on a pooled analysis of three cohorts. CONCLUSIONS: Keeping in mind that
      the usual OSHA acceptable excess risk of serious disease or death for workers is
      0.1%, it is clear that the current standard is far from sufficiently protective
      of workers' health. Perhaps surprisingly, kidney disease emerges as perhaps a
      higher risk than either mortality from silicosis or lung cancer, although the
      data are based on fewer studies.

PMID- 15940720
TI  - Endotoxin exposure and symptoms in wastewater treatment workers.
AB  - BACKGROUND: Wastewater treatment workers can be exposed to biological and
      chemical agents resulting in work-related health effects. The aim of this study
      was to investigate work-related symptoms in these workers. METHODS: Questionnaire
      data of 468 employees from 67 sewage treatment plants is evaluated. Personal
      endotoxin exposure (8 hr measurements; n = 460) was measured in a sample of
      workers in three different periods over 1 year. RESULTS: Endotoxin exposure
      ranged from 0.6 to 2093 endotoxin units (EU)/m(3), the geometric mean exposure
      was low (27 EU/m(3)). Factor analysis yielded three clusters of correlated
      symptoms: "lower respiratory and skin symptoms," "flu-like and systemic
      symptoms," and "upper respiratory symptoms." Symptoms appeared to be more
      prevalent in workers exposed to endotoxin levels higher than 50 EU/m(3). A
      significant dose-response relationship was found for "lower respiratory and skin
      symptoms" and "flu-like and systemic symptoms" (P < 0.05). CONCLUSIONS:
      Wastewater treatment workers reported a wide range of symptoms that may be work
      related. Microbial exposures such as endotoxin seem to play a causal role.

PMID- 15940721
TI  - Age-related differences in work injuries: a multivariate, population-based study.
AB  - BACKGROUND: Many population-based studies find that the rate of work injuries is
      higher among adolescent and young adult workers compared to older adults. The
      present study examines age-related differences in work injuries, with an emphasis
      on adjusting for the potential confounding effects of job characteristics.
      METHODS: Age-related differences in work injuries were examined in a
      representative sample of 56,510 working Canadians aged 15 years and over.
      Respondents reported work-related injuries and job characteristics (e.g.,
      occupation) in the past 12 months. Total hours worked in the past year were
      computed for each worker and accounted for in the logistic regressions. Analyses
      were stratified by gender. RESULTS: For men, adjusting for job characteristics
      substantially reduced, but did not eliminate the elevated risk status of
      adolescent and young adult workers. For women, only young adult women showed an
      elevated risk of work injury with job characteristics controlled. CONCLUSIONS:
      This is one of the few multivariate studies specifically examining contributors
      to age-related differences in work injuries in a population-based sample of
      workers. The substantial reduction in age-work injury association in the fully
      adjusted model suggests that differences in the types of jobs young workers hold
      play a critical role in their high-risk status.

PMID- 15940722
TI  - Potential occupational risks for neurodegenerative diseases.
AB  - BACKGROUND: Associations between occupations and neurodegenerative diseases (NDD)
      may be discernable in death certificate data. METHODS: Hypotheses generated from
      1982 to 1991 study were tested in data from 22 states for the years 1992-1998.
      Specific occupations and exposures to pesticides, solvents, oxidative stressors,
      magnetic fields, and welding fumes were evaluated. RESULTS: About one third
      (26/87) of the occupations hypothesized with neurodegenerative associations had
      statistically significant elevated mortality odds ratios (MOR) for the same
      outcome. Occupations with the largest MORs were (a) for presenile dementia (PSD)
      dentists, graders/sorters (non-agricultural), and clergy; (b) for Alzheimer's
      disease (AD)-bank tellers, clergy, aircraft mechanics, and hairdressers; (c) for
      Parkinson's disease (PD)-biological scientists, clergy, religious workers, and
      post-secondary teachers; and (d) for motor neuron disease (MND)-veterinarians,
      hairdressers, and graders and sorters (non-agricultural). Teachers had
      significantly elevated MORs for all four diseases, and hairdressers for three of
      the four. Non-horticultural farmers below age 65 had elevated PD (MOR = 2.23, 95%
      CI = 1.47-3.26), PSD (MOR = 2.22, 95% CI = 1.10-4.05), and AD (MOR = 1.76, 95% CI
      = 1.04-2.81). Sixty hertz magnetic fields exhibited significant exposure-response
      for AD and, below age 65, for PD (MOR = 1.87, 95% CI = 1.14-2.98) and MND (MOR =
      1.63, 95% CI = 1.10-2.39). Welding had elevated PD mortality below age 65 (MOR =
      1.77, 95% CI = 1.08-2.75). CONCLUSIONS: Support was observed for hypothesized
      excess neurodegenerative disease associated with a variety of occupations, 60 Hz
      magnetic fields and welding.

PMID- 15940723
TI  - Asthma death after spraying polyurethane truck bedliner.
AB  - BACKGROUND: Isocyanate exposure is the most common cause of work-related asthma.
      In 2003, a male in his mid-40s died of an acute asthmatic reaction approximately
      1 hr after he sprayed the inside of a cargo van with an isocyanate-containing
      truck bedliner. This is the first reported death attributable to this type of
      isocyanate application. METHODS: The Michigan Fatality Assessment and Control
      Evaluation (MIFACE) program investigated this work-related fatality to identify
      the factors that contributed to his death. The investigation included site
      visits, personal interviews, and a review of pertinent documents. RESULTS:
      Factors contributing to his death included: the vehicle type; lack of engineering
      controls; lack of a company safety and health program, including a personal
      protective equipment program, medical monitoring, and employee training; and a
      lack of recognition of work-relatedness of the deceased's respiratory problems by
      a health care provider. CONCLUSIONS: This work-related fatality investigation
      demonstrates the need for isocyanate manufacturers/formulators to inform end
      users of their products of appropriate health and safety work practices
      associated with new technologies. In addition, health care providers need more
      education and assistance to recognize and manage work-related asthma.

PMID- 15940724
TI  - Immunosuppression with ALG and CsA is first line treatment in children with SAA
      lacking an HLA identical sibling.

PMID- 15940726
TI  - Stability of gaseous thallium monofluoride as TlF0, TlF+, and TlF2+.

PMID- 15940725
TI  - Response of metastatic recurrent neuroblastoma to nitisinone: a modulator of
      tyrosine metabolism.
AB  - Nitisinone blocks the tyrosine pathway and may be effective in treating
      neuroblastoma. A 33-month-old male with heavily treated metastatic, recurrent, N
      MYC amplified neuroblastoma received nitsinone (0.8 mg/kg/day escalated to 5.0
      mg/kg/day). Dramatic tumor regression and resolution of pain without toxicity
      were observed. At 10 weeks, the tumor progressed. Nitisinone, low dose
      cyclophosphamide and doxorubicin subsequently produced a very good partial
      response. At 18 months the disease progressed. The child succumbed 21 months
      after starting nitisinone. Nitisinone produced an increase in tyrosine and
      catecholamine metabolite (HVA, VMA, and metanephrines) levels. Nitisinone may be
      a promising agent in metastatic neuroblastoma.

PMID- 15940727
TI  - Catalytic, enantioselective, vinylogous aldol reactions.
AB  - In 1935, R. C. Fuson formulated the principle of vinylogy to explain how the
      influence of a functional group may be felt at a distant point in the molecule
      when this position is connected by conjugated double-bond linkages to the group.
      In polar reactions, this concept allows the extension of the electrophilic or
      nucleophilic character of a functional group through the pi system of a carbon
      carbon double bond. This vinylogous extension has been applied to the aldol
      reaction by employing "extended" dienol ethers derived from gamma-enolizable
      alpha,beta-unsaturated carbonyl compounds. Since 1994, several methods for the
      catalytic, enantioselective, vinylogous aldol reaction have appeared, with which
      varying degrees of regio- (site), enantio-, and diastereoselectivity can be
      attained. In this Review, the current scope and limitations of this
      transformation, as well as its application in natural product synthesis, are
      discussed.

PMID- 15940728
TI  - Effect of pressure on the magnetic anisotropy in the single-molecule magnet Mn12
      acetate: an inelastic neutron scattering study.

PMID- 15940729
TI  - Preparation of functionalized aryl magnesium reagents by the addition of
      magnesium aryl thiolates and amides to arynes.

PMID- 15940730
TI  - Single-crystal dendritic micro-pines of magnetic alpha-Fe2O3: large-scale
      synthesis, formation mechanism, and properties.

PMID- 15940731
TI  - Heteroligated Rh(I) tweezer complexes.

PMID- 15940732
TI  - Aerogels from semiconductor nanomaterials.

PMID- 15940733
TI  - Direct catalytic asymmetric Mannich-type reactions of N-(2-hydroxyacetyl)pyrrole
      as an ester-equivalent donor.

PMID- 15940734
TI  - UV spectra and excitation delocalization in DNA: influence of the spectral width.
AB  - The singlet excited states of the model DNA duplex (dA)10.(dT)10 are studied.
      Calculations are performed in the exciton theory framework. Molecular dynamics
      calculations provide the duplex geometry. The dipolar coupling is determined
      using atomic transition charges. The monomer transition energies are simulated by
      Gaussian functions resembling the absorption bands of nucleosides in aqueous
      solutions. Most of the excited states are found to be delocalized over at least
      two bases and result from the mixing of different monomer states. Their
      properties are only weakly affected by conformational changes of the double
      helix. On average, the highest oscillator strength is carried by the upper
      eigenstates. The duplex absorption spectra are shifted a few nanometers to higher
      energies with respect to the spectra of noninteracting monomers. The states with
      larger spatial extent are located close to the maximum of the absorption
      spectrum.

PMID- 15940735
TI  - Solvation of tetraalkylammonium chlorides in acetonitrile-water mixtures: mass
      spectrometry and molecular dynamics simulations.
AB  - The solvation of tetramethylammonium chloride (Me4NCl) and tetra-n-butylammonium
      chloride (Bu4NCl) in water-acetonitrile mixtures was investigated by mass
      spectrometry of clusters isolated from the solution. As far as the positive ions
      are concerned, clusters composed of alkylammonium ions and acetonitrile molecules
      only were observed, even for mixtures with high water content. In contrast, for
      the negative ions, clusters composed of chloride with both water and/or
      acetonitrile molecules were observed. For the smaller system (Me4NCl) we
      performed quantum chemical calculations and molecular dynamics simulations. It
      was found that even though water is present in the solvation shell of Me4N+, only
      acetonitrile has a strong electrostatic interaction with the cation. Water
      molecules around Me4N+ form hydrogen bonds with other water molecules, and they
      interact with Me4N+ mainly via dispersive interactions. These results indicate
      that Me4N+ behaves like a hydrophobic solute. On the other hand, the interaction
      of Cl- with water and acetonitrile is of comparable strength and, in both cases,
      the electrostatic interaction dominates. Herein we demonstrate experimentally and
      theoretically that positive and negative ions give rise to characteristic
      solvation structures in mixed solvents: even a relatively small organic cation,
      such as Me4N+, exhibits a hydrophobic-like solvation shell.

PMID- 15940736
TI  - Valence shell charge concentrations at pentacoordinate d0 transition-metal
      centers: non-VSEPR structures of Me2NbCl3 and Me3NbCl2.
AB  - The molecular structures of the monomeric, pentacoordinated
      methylchloroniobium(IV) compounds Me3NbCl2 and Me2NbCl3 have been determined by
      gas electron diffraction (GED) and density functional theory (DFT) calculations,
      and, for Me3NbCl2, by single crystal X-ray diffraction. Each of the molecules is
      found to have a heavy-atom skeleton in the form of a trigonal bipyramid (TBP)
      with Cl atoms in the axial positions, in accord with their vibrational spectra.
      The TBP is somewhat distorted in the case of Me2NbCl3 with the two axial Nb--Cl
      bonds bent away from the equatorial, slightly shorter Nb--Cl bond. In the case of
      Me3NbCl2, moreover, the X-ray model suggests structural distortions away from the
      idealized C3h geometry, in line with the results of quantum chemical
      calculations. Structure optimizations by DFT calculations and least-squares
      refinement to the GED data yield the following structural parameters
      (calcd/exptl; eq=equatorial; ax=axial; distances in A, angles in degrees; average
      values in brackets): Me3NbCl2, in C(3v) symmetry, Nb--Cl 2.370/2.319(3), Nb--C
      2.173/2.152(4), C--H 1.096/1.124(5), angle-spherical NbCH 109.3/105.2(8), angle
      spherical ClNbC 92.2/93.3(2), angle-spherical CNbC 119.9/119.7(1); Me2NbCl3, in
      C(2v) symmetry, Nb--Cl(ax) 2.361/2.304(5), Nb--Cl(eq) 2.321/2.288(9), Nb--C
      2.180/2.135(9), C--H 1.094/1.12(1), angle-spherical Cl(ax)NbCl(eq) 98.5/96.5(6),
      angle-spherical CNbC 121.0/114(2), angle-spherical NbCH 108.9/109(2). The
      electronic structures of Me2NbCl3 and Me3NbC(2 have been explored by rigorous
      analysis of both the wavefunction and the topology of the electron density,
      employing DFT calculations. Hence the structures of these compounds are shown to
      reflect repulsion between the Nb--C and Nb--Cl bonding electron density and
      charge concentrations induced by the methyl ligands in the valence shell of the
      Nb atom and arising mainly from use of Nb(4d) functions in the Nb--C bonds.

PMID- 15940737
TI  - Structure and bonding of zinc antimonides: complex frameworks and narrow band
      gaps.
AB  - We investigated crystal structure relationships, phase stability and chemical
      bonding of the thermoelectric materials ZnSb, alpha-Zn4Sb3, and beta-Zn4Sb3 by
      means of first principles calculations. The structures of these materials are
      difficult to rationalise. This is especially true for beta-Zn4Sb3 because of the
      presence of vacancies and interstitial atoms. We recognised rhomboid rings Zn2Sb2
      as central structural building units present in all materials. Importantly, these
      rings enable to establish a clear relationship between disordered beta-Zn4Sb3 and
      ordered low-temperature alpha-Zn4Sb3. Concerning the phase stability of Zn4Sb3 we
      identified a peculiar situation: alpha-Zn4Sb3 is metastable and beta-Zn4Sb3 can
      only be thermodynamically stable when its structural disorder accounts for a
      large entropy contribution to free energy. According to their electronic
      structure zinc antimonides represent heteroatomic framework structures with a
      modest polarity. The peculiar electronic structure of Zn/Sb systems can also be
      modelled by Al/Si systems. The high coordination numbers in the frameworks
      implies the presence of multicentre bonding. We developed a simple bonding
      picture for these frameworks where multicentre bonding is confined to rhomboid
      rings Zn2Sb2.

PMID- 15940738
TI  - Solution- and solid-phase synthesis of radicicol (monorden) and pochonin C.
AB  - A modular synthesis for pochonin C and radicicol is reported. The two natural
      products were prepared in seven and eight steps, respectively, from three readily
      available fragments. Alternative syntheses of these compounds were achieved using
      a combination of polymer-bound reagents and solid phase reactions. The
      conformation of the two natural products was studied and compared by using 2D NMR
      spectroscopy.

PMID- 15940739
TI  - Cervimycin A-D: a polyketide glycoside complex from a cave bacterium can defeat
      vancomycin resistance.
AB  - Cervimycins A-D are novel polyketide glycosides with significant activity against
      multi-drug-resistant staphylococci and vancomycin-resistant enterococci. They are
      produced by a strain of Streptomyces tendae, isolated from an ancient cave. The
      structures of the cervimycins were determined by performing extensive NMR and
      chemical degradation studies. All cervimycins have a common tetracyclic
      polyketide core that is substituted with unusual di- and tetrasaccharide chains,
      composed exclusively of trideoxysugars; however, they differ in the acetyl and
      carbamoyl ring substituent and in the highly unusual terminal methylmalonyl and
      dimethylmalonyl residues.

PMID- 15940740
TI  - Complementary medicine use by Australian women with gynaecological cancer.
AB  - AIMS AND OBJECTIVES: Social and cultural factors are identified that impact on
      complementary therapy use among Australia-born and immigrant women diagnosed with
      gynaecological cancer. METHODS: A qualitative study design including in-depth
      interviews with women diagnosed with gynaecological cancer (N=53) and participant
      observation was conducted. RESULTS: Approximately one-third of women utilized
      complementary and alternative medicine, with this being determined by current
      health concerns and health beliefs related to the efficacy of different
      modalities. Four types of complementary therapy users emerged: consequential,
      therapeutic, informed and exploratory. CONCLUSION: There was a relatively low
      uptake of complementary treatments. Choice was influenced by women's socio
      demographic background, clinical and personal history, lack of personal
      experiences of gynaecological cancer among study participants' kin and friends,
      and lack of popular alternative literature on such cancer.

PMID- 15940742
TI  - A qualitative exploration of the cancer experience among long-term survivors:
      comparisons by cancer type, ethnicity, gender, and age.
AB  - BACKGROUND: To elucidate meanings ascribed to the cancer experience by long-term
      survivors. METHODS: Semi-structured interviews were conducted with 58 cancer
      survivors (>15 years post-diagnosis). Respondents described how cancer affected
      their quality of life (QOL) generally and in 17 domains. Systematic content
      analyses were conducted to extract themes relating to meanings assigned to the
      cancer experience. Themes were analyzed by cancer type, gender, and age and
      confirmed using quantitative assessments of self-rated health and QOL. RESULTS:
      Four themes were identified: Personal Growth, That's Life. Relinquishing Control,
      and Resentment. Women more frequently acknowledged Personal Growth, and men more
      often indicated minimal impact on their lives (That's Life). Older survivors were
      disproportionately classified as That's Life and younger survivors as Personal
      Growth. No differences were observed by cancer type or ethnicity. Those who saw
      cancer as personal growth had the highest QOL, while those who resented cancer
      had the lowest QOL. CONCLUSIONS: Most long-term survivors retrospectively report
      that cancer either positively influenced their lives or had little long-term
      impact. Those who express Resentment report that pain, physical deformities, and
      social isolation significantly reduced their QOL. This qualitative study
      highlights how cancer survivors incorporate the cancer experience within their
      overall lives.

PMID- 15940743
TI  - Subclinical atherosclerosis in systemic lupus erythematosus.

PMID- 15940746
TI  - Silicone breast implants.

PMID- 15940748
TI  - Temporal arteritis associated with systemic necrotizing vasculitis.

PMID- 15940751
TI  - Mycophenolate mofetil: a magic bullet for lupus?

PMID- 15940752
TI  - Value of homogenous populations for gene identification in complex rheumatic
      diseases.

PMID- 15940753
TI  - Problems with the definition of axial and peripheral disease patterns in
      psoriatic arthritis.

PMID- 15940754
TI  - An editorial is a golden opportunity.

PMID- 15940755
TI  - Work limitations in the outcome assessment of rheumatoid arthritis.

PMID- 15940756
TI  - Familial seropositive rheumatoid arthritis in North American Native families:
      effects of shared epitope and cytokine genotypes.
AB  - OBJECTIVE: A number of North American native (NAN) populations have high
      prevalence rates of both rheumatoid arthritis (RA) and the shared epitope (SE).
      We examined the phenotype and familial incidence of RA in a NAN population, and
      investigated how the SE and cytokine genes may affect disease risk within
      affected families. METHODS: NAN patients with seropositive RA or polyarthritis
      rheumatoid factor (RF) positive juvenile idiopathic arthritis (JIA) were
      identified from clinical databases. Patients were recruited consecutively as they
      presented for clinic visits. Family pedigrees were constructed and consenting
      relatives were interviewed and examined. The risk of RA within families was
      calculated by multiple logistic regression. Input variables were the SE and
      cytokine genotypes. Probands and affected relatives were entered as the affected
      group, and unaffected relatives within families as the unaffected group. Results
      were confirmed among unrelated subjects, i.e., unrelated patients and unaffected
      relatives of other probands. RESULTS: The familial prevalence of RA was 0.50 (95%
      confidence intervals 0.30, 0.70) among 28 families studied. The interleukin 10
      (IL-10) promoter -1082 G/A genotype decreased the odds of RA relative to the A/A
      genotype in affected families (OR 0.247, 95% CI 0.081, 0.751; p = 0.014) and
      among unrelated subjects (OR 0.203, 95% CI 0.064, 0.640; p = 0.006). The G/G
      genotype yielded an OR of 0.093 (95% 0.013, 0.676; p = 0.019) among unrelated
      subjects. The SE had no effect in these calculations. CONCLUSION: There was a
      high familial prevalence of RA in this NAN cohort. In susceptible NAN families,
      the risk of RA was reduced by IL-10 genotypes, whereas the SE did not affect
      risk. Study of healthy NAN controls is required to determine if these conclusions
      apply to this NAN population as a whole.

PMID- 15940757
TI  - Glutathione S-transferase M1, T1, and P1 genotypes and rheumatoid arthritis.
AB  - OBJECTIVE: To determine the effects of genetic polymorphisms of glutathione S
      transferase (GST) M1, GSTT1, and GSTP on risk and severity of rheumatoid
      arthritis (RA) in a Korean population. METHODS: A total of 258 patients with RA
      and 400 disease-free controls were enrolled. GST genotypes were determined by
      RFLP-PCR. HLA-DRB 1 typing and further subtyping of all alleles was performed
      using sequence-specific oligonucleotide probe hybridization after PCR. Severity
      of RA among cases was assessed by Steinbrocker anatomical stage. Risk was
      assessed by calculating the age and sex adjusted odds ratio (OR) and 95%
      confidence intervals (CI). RESULTS: The OR for risk of RA with the GSTM1-null
      genotype was 1.40 (95% CI 1.02- 1.92, p = 0.04), and 1.86 (95% CI 1.12- 3.09, p =
      0.005) among individuals without the shared epitope (SE). Among patients with RA,
      the OR for risk of severe RA for the GSTM1-null genotype was 2.45 (95% CI 1.04-
      5.77, p = 0.02). No association was observed between the GSTT1 or GSTP1 genotypes
      and either risk or severity of RA. CONCLUSION: These results suggest that the
      deletion polymorphism of GSTM1 is associated with increased susceptibility for
      RA, particularly among individuals who are not carriers of the HLA-DRB 1 SE.

PMID- 15940758
TI  - Mononuclear cell response to lipopolysaccharide in patients with rheumatoid
      arthritis: relationship with tristetraprolin expression.
AB  - OBJECTIVE: To analyze tumor necrosis factor-alpha (TNF-alpha) synthesis by
      mononuclear cells stimulated with lipopolysaccharide (LPS) in patients with
      rheumatoid arthritis (RA). METHODS: TNF-alpha molecular expression and
      extracellular release were assessed in the peripheral blood mononuclear cells
      (PBMC) of 27 RA patients and 16 healthy blood donor controls during 8 hours of
      LPS stimulation. We also analyzed the mRNA expression of tristetraprolin (TTP),
      the major TNF-alpha mRNA destabilizing factor. TNF receptor p75 (TNFR 2) plasma
      concentrations were also tested in all patients. RESULTS: Controls and patients
      demonstrated a comparable wide range of TNF-alpha release capability, but
      patients achieved the peak value of protein release more quickly. Defining the
      median TNF-alpha release in controls as the cutoff value to distinguish high and
      low LPS-induced TNF-alpha-releasing phenotypes, patients with early RA (disease
      duration < 1 yr) belonged mainly to the low TNF-alpha producer subgroup, whereas
      patients with long-standing RA (> 1 yr) were prevalently high TNF-alpha
      producers. TTP molecular expression was higher in patients with shorter, than in
      patients with longer, disease duration. The profile of TNF-alpha release in
      patients with early RA changed significantly when retested after 6 months of
      therapy, while patients with long-standing disease maintained the same behavior
      as at baseline. Finally, a baseline low TNF-alpha-producer phenotype predisposed
      to a better responsiveness to disease modifying antirheumatic drugs. CONCLUSION:
      The LPS-induced TNF-alpha-releasing phenotype differs between cells obtained from
      RA patients with different disease durations and seems to influence the
      therapeutic outcome.

PMID- 15940759
TI  - Work limitations among working persons with rheumatoid arthritis: results,
      reliability, and validity of the work limitations questionnaire in 836 patients.
AB  - OBJECTIVE: To describe workplace limitations and the validity and reliability of
      the Work Limitations Questionnaire (WLQ) in persons with rheumatoid arthritis
      (RA). METHODS: A total of 836 employed persons with RA reported clinical and work
      related measures and completed the WLQ, a 25 item questionnaire that assesses the
      impact of chronic health conditions on job performance and productivity.
      Limitations are categorized into 4 domains: physical demands (PDS), mental
      demands (MDS), time management demands (TMS), and output demands (ODS), which are
      then used to calculate the WLQ index. RESULTS: Of the 836 completed WLQ, about
      10% (85) could not be scored, as more than half the items in each domain were not
      applicable to the patient's job. Demographic and clinical variables were
      associated with missing WLQ scores including older age (OR 1.7, 95% CI 1.3-2.1),
      male sex (OR 1.9, 95% CI 1.2-3.0), and Health Assessment Questionnaire (HAQ)
      scores (OR 1.4, 95% CI 1.0-2.0). Work limitations were present in all work
      domains: PDS (27.5%), MDS (15.7%), ODS (19.4%), and TMS (28.6%), resulting in a
      mean WLQ index of 5.9 (SD 5.6), which corresponds to a 4.9% decrease in
      productivity and a 5.1% increase in work hours to compensate for productivity
      loss. The WLQ index was inversely associated with Medical Outcomes Study Short
      Form 36 (SF-36) Mental Component Score (MCS; r = -0.60) and Physical Component
      Score (PCS; r = -0.49). Fatigue (0.5), pain (0.46), and HAQ (0.56) were also
      significantly associated with the WLQ index. Weaker associations were seen with
      days unable to perform (0.29), days activities cut down (0.38), and annual income
      (-0.10). CONCLUSION: The WLQ is a reliable tool for assessing work productivity.
      However, persons with RA tend to select jobs that they can do with their RA
      limitations, with the result that the WLQ does not detect functional limitations
      as well as the HAQ and SF-36. The WLQ provides special information that is not
      available using conventional measures of assessment, and can provide helpful
      knowledge about individual patient problems in the workplace. Whether this
      information will have greater predictive ability and clinical relevance compared
      with surrogate measures such as the HAQ and SF-36 has not been determined, but
      should be the subject of future studies.

PMID- 15940760
TI  - Comorbid depression is an independent risk factor for mortality in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: Whether comorbid depression increases mortality in patients with
      rheumatoid arthritis (RA) is unknown. Our objective was to determine whether the
      presence of depression predicted mortality in patients with RA. METHODS: We
      followed 1290 consecutive outpatients with RA who met our stringent inclusion
      criteria during an 18-year observation period. Since 1981, demographic, clinic,
      and self-report data were collected and entered into a computer database at the
      time of each clinic visit. The comorbidity data were consistently recorded
      beginning in 1991. Our primary independent variable was the mean of the Arthritis
      Impact Measurement Scales (AIMS) depression scores during the first 4 years of
      entry into the clinic cohort (average 4-year depression). Data were analyzed
      using Cox proportional hazard models. RESULTS: After adjusting for covariates,
      the hazard ratio (HR) for each unit increase in the average 4-year depression
      score on mortality was 1.14 (p < 0.0001). Using only the data obtained from 1991
      to 2003, the mortality risk was slightly increased (HR 1.35, p < 0.0001). To
      reduce residual confounding due to RA disease activity and/or comorbid medical
      conditions, we then excluded deaths during the first 2 years after study onset.
      With this method, the HR for the average 4-year depression remained significant
      (HR 1.35, p < 0.0001). Because an AIMS depression score > or = 4 is consistent
      with clinical depression, we analyzed the dataset using the average 4-year
      depression score as a dichotomous variable (score < 4 or > or = 4). The HR of
      clinical depression on mortality was 2.2 (95% CI 1.2- 3.9, p = 0.01). CONCLUSION:
      Depression increases the risk of mortality in RA. Our study highlights the
      importance of comorbid depression in patients with RA.

PMID- 15940761
TI  - Rheumatoid arthritis: evidence for bone loss in premenopausal women.
AB  - OBJECTIVE: To assess bone mineral density (BMD) status in patients with
      rheumatoid arthritis (RA). METHODS: Rheumatoid factor-positive premenopausal
      women with RA meeting the American College of Rheumatology criteria were
      enrolled. Exclusion criteria included diseases or drugs that affect BMD, except
      for glucocorticoids, and smoking. Evaluation consisted of a questionnaire,
      physical examination, and laboratory tests. Lumbar spine and right proximal femur
      BMD were measured with a DPX-Lunar DEXA scanner. Data were analyzed by Student t
      test, chi-square, and multivariate analysis. RESULTS: We studied 78 patients with
      RA and 39 controls; 82% were Caucasian, with mean age 35.5 +/- 6.7 years, and
      mean disease duration 48 +/- 51 months. Among patients, 74.4% had been treated
      with glucocorticoids, with a mean daily dose of 9.7 +/- 5.9 mg. Mean lumbar spine
      BMD was 1.157 +/- 0.124 g/cm2 in the RA patients, and 1.223 +/- 0.147 g/cm2 in
      controls (p < 0.01). Mean right proximal femur BMD did not differ significantly.
      Lumbar spine osteopenia correlated with "no physical activity at work" status,
      low body weight, and duration of glucocorticoid therapy. Femoral neck osteopenia
      correlated with "no physical activity at work" status, Steinbrocker class III,
      erosions of the hands, and high erythrocyte sedimentation rate (ESR).
      Trochanteric osteopenia correlated with "no physical activity at work" status,
      erosions on hand radiographs, low body weight, high ESR, and anemia. CONCLUSION:
      Patients with RA of relatively short disease duration already exhibited
      significantly lower lumbar spine BMD. The identification of prognostic markers
      for bone loss in patients with RA should not only prompt early therapeutic
      intervention, but also facilitate early preventive measures.

PMID- 15940762
TI  - Parenteral gold preparations. Efficacy and safety of therapy after switching from
      aurothioglucose to aurothiomalate.
AB  - OBJECTIVE: For reasons of insufficient quality of the raw material,
      aurothioglucose was withdrawn from the Dutch market at the end of 2001.
      Aurothiomalate became available as an alternative preparation. We followed a
      cohort of patients during the first year after switching from aurothioglucose to
      aurothiomalate to study efficacy and tolerability. METHODS: Patients were
      observed at baseline and at 3 and 12 months after switching. At each visit, data
      on adverse drug reactions (ADR), withdrawal, and disease activity were collected.
      RESULTS: In total 120 patients were included [age 63(SD 15) yrs, 68% female, 93%
      with rheumatoid arthritis, duration of disease 15 (SD 9) years, 82% IgM
      rheumatoid factor-positive, with 9 (SD 9, range 0.1-45) yrs of previous
      aurothioglucose therapy]. Nineteen patients (16%) reported an ADR taking
      aurothiomalate not previously experienced with aurothioglucose, the most
      frequently reported being pruritus, dermatitis/stomatitis, and
      chrysiasis/hyperpigmentation. Twenty-nine patients (24%) withdrew from
      aurothiomalate within 12 months of followup for reasons of inefficacy (14%), ADR
      (7%), or disease in state of remission (3%). Kaplan-Meier estimates show
      aurothiomalate survival rates of 78.5% after 12 months. No statistically
      significant differences between the disease activity indicators during followup
      visits compared with the baseline visit were detected for the patients continuing
      aurothiomalate. CONCLUSION: Within the first 12 months after switching from
      aurothioglucose, 24% of patients withdrew from aurothiomalate. Sixteen percent of
      patients reported novel ADR. For the population continuing to take aurothiomalate
      no clinically relevant changes in disease activity were recorded after switching.

PMID- 15940763
TI  - Can progressive resistance training reverse cachexia in patients with rheumatoid
      arthritis? Results of a pilot study.
AB  - OBJECTIVE: . A Phase II trial was performed as a preliminary test of the efficacy
      and safety of progressive resistance training (PRT) as adjunct treatment for
      rheumatoid cachexia. METHODS: Ten mildly disabled patients with well-controlled
      rheumatoid arthritis (RA) trained, on average, 2.5 times per week for 12 weeks.
      Ten age and sex matched RA patients with similar disease characteristics were non
      randomly assigned to a control group. Body composition, physical function, and
      disease activity were assessed pre and post intervention period. RESULTS: Between
      group comparisons at followup by ANCOVA using baseline scores as covariate showed
      significant increases in fat-free mass (+1253 g, p = 0.004), total body protein
      (+1063 g, p = 0.044), and arm (+280 g, p = 0.005) and leg (+839 g, p = 0.001)
      lean mass (a proxy measure of total body skeletal muscle mass) in response to PRT
      with no exacerbation of disease activity. There was also a trend for loss of fat
      mass in the trunk (-752 g, p = 0.084) and a significant reduction in percent body
      fat (-1.1%, p = 0.047). Changes in body composition were associated with
      improvements in various measures of physical function. CONCLUSION: Intense PRT
      with adequate volume seems to be an effective and safe intervention for
      stimulating muscle growth in patients with RA. Pending confirmation of these
      results in a larger randomized controlled trial that includes patients with more
      active and severe disease, a similar PRT program should be included in the
      management of RA as adjunct treatment for cachexia.

PMID- 15940764
TI  - Age adjustment corrects for apparent differences in erythrocyte sedimentation
      rate and C-reactive protein values at the onset of seropositive rheumatoid
      arthritis in younger and older patients.
AB  - OBJECTIVE: To evaluate the effect of age adjustment on baseline erythrocyte
      sedimentation rate (ESR) and C-reactive protein (CRP) in patients with late-onset
      rheumatoid arthritis (LORA, age > or = 55 yrs) and younger-onset RA (YORA, age <
      55 yrs) in a cohort with early, rheumatoid factor (RF) positive RA that has not
      received disease modifying antirheumatic drugs (DMARD). METHODS: In an ongoing
      prospective cohort study of 263 patients with seropositive RA who were enrolled
      within 14 months of symptom onset, baseline assessments included ESR, CRP, tender
      and swollen joint counts, and functional status. Westergren ESR determinations
      were performed in the rheumatologist's office or in a local laboratory using
      appropriate methods. CRP were performed at the Specialty Laboratories in Santa
      Monica, CA, using Behring nephelometry. Percentages of patients with greater than
      the upper limit of normal (ULN) laboratory values using both age-unadjusted and
      age-adjusted ESR and CRP values were determined. The late-onset and younger-onset
      RA patients were compared using Wilcoxon rank-sum and chi-square tests. RESULTS:
      At study entry, both the YORA and LORA patients had comparable symptom duration,
      disease activity scores, tender and swollen joint counts, and Health Assessment
      Questionnaire values. RF, CRP, and ESR were significantly higher (p < 0.05) in
      LORA patients. Although the percentages of patients with age-unadjusted ESR and
      CRP above ULN were higher in LORA patients, the percentages exceeding the age
      adjusted ULN did not differ significantly between the YORA and LORA groups.
      CONCLUSION: In patients with late-onset and younger-onset RA with similar disease
      duration and severity, the apparent discrepancy in elevation of both the baseline
      ESR and CRP disappears after age-adjustment.

PMID- 15940765
TI  - Diagnosing late onset rheumatoid arthritis, polymyalgia rheumatica, and temporal
      arteritis in patients presenting with polymyalgic symptoms. A prospective
      longterm evaluation.
AB  - OBJECTIVE: . To examine for demographic and clinical differences between late
      onset rheumatoid arthritis (LORA), polymyalgia rheumatica (PMR), and temporal
      arteritis (TA) patients presenting with polymyalgic symptoms (PMS) and to
      identify baseline clinical and laboratory features that would lead to a more
      accurate final diagnosis. METHODS: Three hundred forty-nine consecutive patients
      with new onset of symptoms suggestive of LORA, PMR, or TA presenting at or above
      age 60 years were enrolled in a prospective study. RESULTS: During followup, 9
      patients diagnosed initially as PMR developed LORA (giving a final total of 145),
      5 patients initially diagnosed as LORA changed diagnosis to PMR (final total
      147), and 29 patients had PMS that predated TA symptoms (final total 57). The
      delay in diagnosis ranged from 1 to 30 months. DRB1*04 was associated with
      development of both LORA and TA. CONCLUSION: In about 10% of patients the correct
      diagnosis of LORA, PMR, and TA in those presenting with PMS may be delayed due to
      similarities in initial clinical presentation. Longterm followup is essential to
      establish correct diagnosis. Laboratory tests tend to be unhelpful, although a
      positive rheumatoid factor or persistently raised plasma viscosity despite
      steroids might indicate RA, and the presence of HLA-DRB1*04 may indicate
      underlying RA or TA.

PMID- 15940766
TI  - Mycophenolate mofetil in systemic lupus erythematosus: efficacy and tolerability
      in 86 patients.
AB  - OBJECTIVE: To assess the indications, efficacy, and tolerability of mycophenolate
      mofetil (MMF) in patients with systemic lupus erythematosus (SLE) resistant to
      other immunosuppressive therapy. METHODS: Records of 93 patients with SLE were
      retrospectively reviewed. Seven patients were excluded. The remaining 86 patients
      received other immunosuppressive drugs before MMF. Efficacy was measured by
      changes in daily oral prednisolone dose, European Consensus Lupus Activity
      Measurement Index (ECLAM), erythrocyte sedimentation rate (ESR), C-reactive
      protein, and dsDNA antibody titer. In renal patients, changes in serum
      creatinine, creatinine clearance, chromium-51 EDTA glomerular filtration rate
      (EDTA-GFR), and 24 hour urine protein excretion were also evaluated. RESULTS:
      Indications for MMF were mainly renal involvement (59% of patients), uncontrolled
      disease activity (14%), and other SLE related manifestations (13%). Overall, we
      found a significant reduction in the steroid dosage, ECLAM, ESR, and anti-dsDNA
      antibody titer. Renal patients (n = 35) showed a significant reduction in urinary
      24 hour protein excretion. Levels of serum creatinine, creatinine clearance, and
      EDTA-GFR showed no significant change during treatment. Thirty-seven patients
      (42.8%) developed adverse events. Gastrointestinal intolerance in 25 (29%) and
      infections in 20 (23.2%) were the most frequent. The drug was discontinued in 14
      (16.3%) patients due to side effects and 6 patients discontinued MMF because they
      achieved disease remission and were trying to conceive. MMF was stopped due to
      lack of efficacy in 12 patients. CONCLUSION: Our data suggest that MMF is a good
      therapeutic alternative for patients with SLE and renal involvement or refractory
      disease activity.

PMID- 15940767
TI  - Seasonal variation of lupus nephritis: high prevalence of class V lupus nephritis
      during the winter and spring.
AB  - OBJECTIVE: Systemic lupus erythematosus is a multisystem disease with many
      clinical variations, including renal involvement. Our aim was to determine
      whether lupus nephritis (LN) has a specific seasonality. METHODS: Reports of
      renal biopsies performed from 1990 to 2002 were reviewed. Three hundred and
      seventy-three patients with class II, III, IV, and V LN were identified. Using
      the modified WHO classification of LN, diagnoses were tabulated and the
      seasonality (season of diagnosis) of LN was statistically analyzed. RESULTS:
      Class IV LN was detected in 179 patients (48%), class II in 63 patients (16.9%),
      class III in 73 patients (19.57%), and class V in 74 patients (19.9%). No
      difference could be detected in the number of patients diagnosed in each season
      when all 373 patients were analyzed as one group. The number of patients with
      class IV LN was higher during summer and fall than during the winter and spring.
      In contrast, a higher number of patients with class V LN were observed during the
      winter and spring seasons than during the summer and fall seasons. The percentage
      of patients with class V LN was significantly higher during winter and spring
      than during summer and fall. A similar, though non-significant, trend was seen
      for class III LN. A striking parallelism was found between the month of
      occurrence of class III and class V LN. The monthly distribution of the
      percentage of patients in each month with class III and V LN showed a significant
      correlation. The monthly distribution of patients with class IV LN was different
      from those with either class III or V LN. CONCLUSION: We found that the
      prevalence of class V LN was significantly higher and that of class III LN non
      significantly higher in winter and spring. Parallelism between the monthly
      occurrences of class III and class V may suggest a common trigger. Analysis of
      the seasonality of LN may contribute to the understanding of the pathogenesis of
      LN, which may be multifactorial, as the different classes of LN represent
      different types of glomerular injury. Further studies are needed to clarify this
      potentially important observation.

PMID- 15940768
TI  - Factor XIII in primary antiphospholipid syndrome.
AB  - OBJECTIVE: To evaluate the clinical significance of factor XIII (FXIII) in
      primary antiphospholipid syndrome (APS). METHODS: A cross-sectional study
      including patients with primary APS (n =29), persistent carriers of idiopathic
      antiphospholipid antibodies (aPL) with no history of thrombosis (n = 14),
      thrombotic patients with inherited thrombophilia (n =24), healthy controls (n
      =28), and patients with mitral and aortic valve prosthesis (n =32, as controls
      for FXIII only). FXIII and fibrinogen were measured by functional assays: IgG
      anticardiolipin antibody (aCL), IgG anti-beta2-glycoprotein I (anti-beta2-GPI),
      and plasminogen activator inhibitor (PAI) by immunoassay; and paraoxonase
      activity by paranitrophenol formation. Intima-media thickness (IMT) of carotid
      arteries was determined by high resolution sonography. RESULTS: FXIII activity
      (FXIIIa) was highest in primary APS (p= 0.001), particularly in patients with
      multiple occlusions (n =12) versus those with single occlusion (158 +/- 45% vs
      118 +/- 38%; p=0.02). In primary APS, FXIII positively correlated with PAI
      (p=0.003) and fibrinogen (p = 0.005). Similarly in the thrombotic control group,
      FXIIIa correlated with PAI (p =0.05) and fibrinogen (0.007). In primary APS,
      FXIIIa was related to the IMT of all carotid artery segments (p always < 0.01).
      In thrombotic controls FXIIIa correlated only to the IMT of the common carotid (p
      =0.01). In primary APS, FXIIIa was strongly associated with IgG aCL and IgG anti
      beta2-GPI (p=0.005 for both). These associations were weaker in the aPL group
      (FXIIIa with IgG aCL, p= 0.02, with IgG anti-beta2-GPI, p=0.04). CONCLUSION:
      Enhanced FXIII activity may contribute to atherothrombosis in primary APS via
      increased fibrin/fibrinogen cross-linking. This pathway is not exclusive to
      primary APS, being present also in thrombotic controls, but the presence of IgG
      aPL may favor a higher degree of FXIIIa activation in the primary APS group.

PMID- 15940769
TI  - Vasculitis and expression of vascular cell adhesion molecule-1, intercellular
      adhesion molecule-1, and E-selectin in salivary glands of patients with Sjogren's
      syndrome.
AB  - OBJECTIVE: We investigated the relationship between clinical symptoms and the
      grade of histopathological damage and expression of adhesion molecules in
      salivary glands of patients with Sjogren's syndrome (SS). METHODS: We studied
      untreated and recently diagnosed patients with primary (n =20) and secondary SS
      [10 with SS and rheumatoid arthritis (RA); 10 with SS and systemic lupus
      erythematosus (SLE)] and 3 healthy controls. Salivary gland biopsies were
      performed in patients and controls and clinical data were obtained. Salivary
      gland biopsies were assessed for lymphocyte focus score and expression of
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and E-selectin. In serum, antinuclear antibodies, rheumatoid factor,
      anti-Ro and anti-La antibodies, anti-alpha-fodrin IgA and IgG antibodies, and
      gamma-globulin concentrations were measured. RESULTS: In salivary gland samples,
      ICAM-1 was expressed on vascular endothelial cells and lymphocyte foci, while
      VCAM-1 was expressed on vascular endothelial cells and follicular dendritic
      reticulin cells. There was a positive correlation between lymphocyte focus score
      and ICAM-1 expression (p < 0.05). We detected correlation between expression of
      ICAM-1 and VCAM-1, and the expression of VCAM-1 was significantly related to
      vasculitis (p < 0.05). The areas of E-selectin expression and the dispersion and
      severity of staining were not correlated with the focus score or with patients'
      clinical features (p > 0.05). There was no correlation between the staining and
      autoantibody positivity and gamma-globulin levels. CONCLUSION: ICAM-1 may be
      important for lymphocyte recruitment and glandular damage and VCAM-1 may be
      important for the development of vasculitis in patients with SS.

PMID- 15940770
TI  - Abnormal distribution of aquaporin-5 in salivary glands in the NOD mouse model
      for Sjogren's syndrome.
AB  - OBJECTIVE: To localize aquaporin-5 in healthy salivary gland acinar cells and to
      check if it is abnormally translocated in an experimental NOD mouse model for
      Sjogren's syndrome (SS). METHODS: Healthy BALB/c control mice and autoimmune
      focal adenitis NOD mice were studied. Aquaporin-5 was stained using avidin-biotin
      peroxidase complex and indirect immunofluorescence staining methods, and
      visualized using light and laser scanning confocal microscopy. RESULTS: Aquaporin
      5 was found in the apical domain of the acinar cell plasma membrane in healthy
      BALB/c mice. In contrast, aquaporin-5 was found in the apical and basolateral
      acinar plasma cell membrane in parotid, submandibular, and sublingual glands in
      NOD mice. This was confirmed using laser scanning confocal microscopy for optical
      sectioning and image reconstruction. CONCLUSION: Our findings reveal an abnormal
      translocation of aquaporin-5 in an experimental SS animal model and support
      observations that implied a similar loss of the ordered and polarized expression
      of aquaporin-5 in human SS labial and lacrimal glands.

PMID- 15940771
TI  - Incidence of Churg-Strauss syndrome in asthma drug users: a population-based
      perspective.
AB  - OBJECTIVE: To estimate the incidence of Churg-Strauss syndrome (CSS) among a
      large population of asthma drug users. METHODS: A retrospective study was
      conducted among patients who had been dispensed asthma drugs at 3 managed care
      organizations. Adults who received >or =3 dispensings of an asthma drug during
      any consecutive 12-month period between January 1, 1995 and June 30, 2000 were
      identified. Information on patient age, gender, enrollment status, asthma drugs
      dispensed, and inpatient and outpatient diagnoses and procedures was obtained
      from automated databases. Chart reviews were performed on persons identified by
      combinations of diagnostic and billing codes indicative of CSS. A rheumatologist
      reviewed abstracted information on all subjects; those who met >or =2 American
      College of Rheumatology criteria for CSS were reviewed by 2 clinical experts.
      Each clinical expert independently rated the cases; disagreements were resolved
      by consensus. Cases classified as having "probable/definite" CSS were included in
      these analyses. The incidence of CSS was estimated overall and according to
      patient gender, age, and calendar year. RESULTS: From a population of 184,667
      asthma drug users contributing 606,184 person-years of exposure, 21 incident
      cases of CSS were identified (overall incidence of 34.6 per million person-years;
      95% confidence interval 21.4 to 53.0). Incidence rates did not differ by gender
      and age group. The incidence rates for 1995, 1996, 1997, 1998, 1999, and the
      first 6 months of 2000 were 0, 22, 52, 75, 14, and 14 per million person-years
      respectively. CONCLUSIONS: Results from this population-based study suggest a
      somewhat lower incidence of CSS in asthma drug users than previously reported and
      provides important information as to the risk of developing CSS from a population
      based perspective.

PMID- 15940772
TI  - Inducible nitric oxide synthase polymorphism is associated with susceptibility to
      Henoch-Schonlein purpura in northwestern Spain.
AB  - OBJECTIVE: To assess the contribution of 2 polymorphisms within the inducible
      nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schonlein
      purpura (HSP), and to determine if implications exist with severe systemic
      complications of HSP, in particular with severe renal involvement and permanent
      renal dysfunction (renal sequelae). METHODS: Fifty-eight patients from Northwest
      Spain with primary cutaneous vasculitis classified as HSP were studied. All
      patients were required to have had at least 2 years' followup. Patients and
      ethnically matched controls (n=251) were genotyped by PCR based techniques for a
      multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of
      the NOS2A gene. RESULTS: HSP patients exhibited a significantly increased
      frequency of the NOS2A short (8-11) CCTTTn alleles (OR 1.64, 95% CI 1.09-2.47,
      p=0.017) and genotypes (OR 3.59, 95% CI 1.79-7.20, p=0.0002) compared to
      controls, particularly when patients with nephritis were compared with controls.
      However, when the NOS2A TAAA repeat polymorphism was assessed, no differences
      were found. CONCLUSION: Significant differences in the NOS2A promoter
      polymorphism allele and genotype frequency between HSP patients and controls
      suggest a potential role for this gene in the susceptibility to HSP and in the
      development of nephritis.

PMID- 15940773
TI  - Women's preferences for prevention of bone loss.
AB  - OBJECTIVE: Despite the serious consequences of osteoporosis, few women use
      pharmacologic measures to prevent postmenopausal bone loss. We used an
      interactive computerized questionnaire to examine women's preferences for
      prevention of osteoporosis. METHODS: We administered a choice-based conjoint
      analysis survey (CBCA) to consecutive early postmenopausal women in a shopping
      center. The questionnaire was constructed to measure preferences for
      pharmacologic and nonpharmacologic measures to prevent postmenopausal bone loss.
      Women were also given the option of choosing "none," i.e., to defer or refuse all
      options. Utilities were calculated based on a Hierarchical Bayes model using
      Monte Carlo-Markov chain algorithms. We performed simulations based on women's
      values for specific treatment characteristics to estimate choice. RESULTS: A
      total of 212 women agreed to complete the survey (42% participation rate).
      Between 18% and 47% of the women surveyed (mean age 52+/-5 yrs) were predicted to
      choose once-weekly medications to prevent postmenopausal bone loss, assuming
      treatment confers an absolute lifetime risk reduction in fractures of at least
      10%. CONCLUSION: In this CBCA survey, which derived preferences based on how
      women make tradeoffs between specific treatment characteristics, a significant
      percentage of women were willing to use once-weekly medications to prevent
      postmenopausal bone loss.

PMID- 15940774
TI  - Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with
      osteoarthritis of the knee. A combined analysis of the VACT studies.
AB  - OBJECTIVE: To compare efficacy among 1578 patients with osteoarthritis randomized
      to take acetaminophen 4000 mg (n=269), celecoxib 200 mg (n=523), rofecoxib 12.5
      mg (n=259), or rofecoxib 25 mg (n=527) in a double blind trial [Vioxx,
      Acetaminophen, Celecoxib Trial (VACT2)]. Results were also pooled with the
      similarly designed VACT1 trial. METHODS: Patients evaluated over Days 1 to 6 and
      6 weeks with Patient Global Assessment of Response to Therapy (PGART) and Western
      Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. RESULTS: For
      VACT2, median time to good or excellent PGART response was 6, 5, 4, and 3 days
      for acetaminophen, celecoxib, rofecoxib 12.5 mg, and rofecoxib 25 mg (COX-2
      inhibitors vs acetaminophen, p<or=0.035; rofecoxib 25 mg vs celecoxib, p=0.01).
      WOMAC response over the first 6 days was greater (p < 0.05) with both rofecoxib
      doses than acetaminophen and celecoxib. At Week 6, all COX-2 inhibitors provided
      significantly greater efficacy than acetaminophen. Good or excellent PGART was
      numerically, but not significantly, greater with rofecoxib 25 mg (55.4%) than
      celecoxib (50.6%) at Week 6; a significant difference was seen at Weeks 2 (6.9,
      p=0.022) and 4 (6.7, p=0.027) and over 6 weeks with analysis of all 5 PGART
      categories of response (p=0.035). Rofecoxib 25 mg provided greater response
      (p<0.05) than celecoxib on WOMAC subscales. Pooled analysis of VACT1/VACT2
      demonstrated greater PGART (p=0.023) with rofecoxib 25 mg (56.1%) than celecoxib
      (49.8%) at 6 weeks and greater response to all other PGART and WOMAC endpoints,
      and confirmed superiority of COX-2 inhibitors to acetaminophen. Overall,
      tolerability of the study medications was generally good and similar. There was
      no significant difference between treatment groups in the percentage of patients
      who experienced a clinical adverse experience (AE). The incidence of
      discontinuations due to an AE was significantly lower with celecoxib (2.5%)
      compared to rofecoxib 25 mg (6.3%, p=0.004) or acetaminophen (7.8%, p< 0.001),
      and did not differ significantly from rofecoxib 12.5 mg (4.6%). Discontinuation
      rates due to edema and hypertension related AE were similar among all COX-2
      inhibitors. CONCLUSION: Rofecoxib and celecoxib provided superior efficacy to
      acetaminophen. There was a more rapid and greater response with rofecoxib 25 mg
      than celecoxib 200 mg. Rofecoxib 12.5 mg demonstrated greater efficacy than
      celecoxib 200 mg over the first 6 days, and was similar over 6 weeks. All study
      medications were generally well tolerated.

PMID- 15940775
TI  - The effects of an exercise program for older adults with osteoarthritis of the
      hip.
AB  - OBJECTIVE: . Evaluation of an 8-week exercise program with strength training and
      lifestyle advice for older adults with osteoarthritis (OA) of the hip. Outcome
      measures were pain, hip function, disability, quality of life (QOL), and body
      mass index (BMI). METHODS: Inclusion criteria for this randomized controlled
      trial were: age >or=55 years, clinical diagnosis of OA according to American
      College of Rheumatology criteria, and living independently. Interview and
      physical data were collected at baseline, post-test, and followup (3 mo) by
      trained interviewers and physical therapists with validated instruments: Harris
      Hip Score, Sickness Impact Profile, Groningen Activity Restriction Scale,
      functional tests (walking, timed Up & Go, ascending and descending stairs, and
      toe reaching), and visual analog scales (pain and QOL). Data were analyzed on an
      intention-to-treat basis. Effect sizes were calculated. RESULTS: There were 109
      participants (55 experimental, 54 controls). The 15 participants who dropped out
      were characterized by less tolerance to pain and younger age. The program had a
      positive effect on pain (moderate effect at post-test and small effect at
      followup), hip function (small effect at post-test), self-reported disability
      (small effect at followup), and the timed Up & Go test (small effect at
      followup). It did not affect QOL, other measures of observed disability, or BMI.
      CONCLUSION: The exercise program had positive effects on pain and hip function,
      which are important mediators of disability. This study fulfilled a need for
      older adults with hip OA and provides evidence of the benefit of exercise in the
      management of hip OA.

PMID- 15940776
TI  - A randomized, double-blind, placebo controlled triphosphate in study of oral
      adenosine subacute low back pain.
AB  - OBJECTIVE: To assess the efficacy and safety of oral adenosine triphosphate (ATP)
      in subacute low back pain. METHODS: This was a randomized, double-blind, parallel
      group, placebo controlled clinical trial. The patients were given either ATP 90
      mg once daily (n=81) or placebo (n=80) for one month. The patients were assessed
      3 times during the study period, at days 0, 7, and 30. The primary outcome
      measure was the Roland-Morris Disability Questionnaire (RDQ) at day 30. Secondary
      measures of efficacy included visual analog scale (VAS) pain, overall assessments
      of efficacy by both patient and investigator, and number of dextropropoxyphene
      and acetaminophen combination tablets used as rescue analgesic. RESULTS:
      Regarding the RDQ, the mean values dropped from 10.3 +/-2.8 at baseline to 7.5 +/
      3.8 (day 7) and 5.2 +/-5.2 (day 30) in the ATP group, and from 11.0 +/- 3.5 to
      9.1 +/- 4.2 (day 7) and 6.1 +/- 4.3 (day 30) in the placebo group. The difference
      between the 2 groups was statistically significant at day 7 (p= 0.02) but not at
      day 30 (p=0.2). In other words, the mean changes from baseline were 2.8 +/- 3.1
      and 2.0 +/- 2.6 at day 7 (p=0.06), and 5.1 +/- 3.9 and 5.0 +/- 4.2 at day 30
      (p=0.78) in the ATP group and the placebo group, respectively. There were no
      statistically significant differences in the VAS pain and overall assessments of
      efficacy between groups at any time point during the study. Conversely, there was
      a significant difference in the use of the rescue analgesic between groups, in
      favor of ATP (p=0.04). Oral ATP was well tolerated. CONCLUSION: Oral ATP might
      have an early acting effect in subacute low back pain.

PMID- 15940777
TI  - Lack of association of fibromyalgia with hepatitis C virus infection.
AB  - OBJECTIVE: An association between chronic hepatitis C virus (HCV) infection and
      fibromyalgia (FM) remains controversial, mainly because previous studies were
      based on prevalent case series or comparisons with less than optimal control
      groups. We investigated whether there might be an association between chronic HCV
      infection and FM. METHODS: We prospectively investigated the prevalence of HCV
      infection in a series of 115 patients with FM and compared it with the prevalence
      in the general population of our community reported in the same period. Anti-HCV
      antibodies were determined by ELISA. In positive cases, infection was confirmed
      by recombinant immunoblot assay and HCV-RNA was detected by PCR using sera
      samples. Differences between prevalence rates were assessed by chi-square test.
      RESULTS: HCV infection was confirmed in 3 of 115 patients with FM (2.6%). Two of
      these patients (1.74%) had active HCV infection shown by the presence of viral
      RNA in serum, whereas HCV RNA was undetectable in the third patient. In these
      cases, liver disease had previously been undiagnosed and HCV infection manifested
      itself by extrahepatic symptoms. Although the prevalence of HCV infection was
      slightly higher in patients with FM than in the general population in the age
      groups 25-44 and 45-64 years, when we compared prevalence rates in the total
      group and the different age groups, no statistically significant differences were
      found. CONCLUSION: From our results, it seems unlikely that HCV infection plays a
      pathogenic role in FM.

PMID- 15940778
TI  - Early disease course and predictors of disability in juvenile rheumatoid
      arthritis and juvenile spondyloarthropathy: a 3 year prospective study.
AB  - OBJECTIVE: . To describe the 3 year disease course in early juvenile rheumatoid
      arthritis (JRA) and juvenile spondyloarthropathy (JSpA), to compare the health
      status after 3 years of followup with that of normal controls, and to investigate
      the relationship between physical function at followup and disease
      characteristics recorded during the first 6 months. METHODS: One hundred and
      ninety-seven children (median age 6:6 yrs) with JRA and JSpA and disease duration
      <1.5 years were examined by a pediatric rheumatologist every 6 months for a
      median of 3.1 years. Controls were randomly selected from the National Population
      Register. Physical and psychosocial health was assessed by means of the Child
      Health Questionnaire and the Childhood Health Assessment Questionnaire (CHAQ).
      Disease course was analyzed by analysis of variance for repeated measurements.
      RESULTS: Health status and disease activity improved over time. Treatment with
      disease modifying antirheumatic drugs was started in 58% of the patients at
      baseline. Patients with persistent oligoarthritis had the most favorable disease
      course. The patients with juvenile ankylosing spondylitis (JAS), syndrome of
      seronegative enthesopathy and arthropathy (SEA), and rheumatoid factor (RF)
      positive polyarthritis had the poorest health status. A significant improvement
      for the whole group was observed after 3 years in all measures of disease
      activity and health status, except pain. Patients had poorer physical function
      and general health and more pain than controls. Predictors of reduced physical
      function at followup were a high CHAQ disability index and a poor well-being
      assessed during the first 6 months. CONCLUSION: Health status and disease
      activity improved over time in patients under medical treatment. The patients
      with JAS/SEA and RF positive polyarthritis had poorer health than the patients in
      other subtypes. A high disability index and a poor well-being at baseline
      predicted reduced physical function after 3 years.

PMID- 15940779
TI  - Leflunomide induced acute interstitial pneumonia.
AB  - We describe a 54-year-old woman with rheumatoid arthritis (RA), who developed
      acute respiratory failure 2 weeks after cessation of 6-week treatment with
      leflunomide. We diagnosed interstitial pneumonia, probably induced by leflunomide
      because acute respiratory failure was preceded by elevated serum liver enzyme
      concentration and hypertension. She showed dramatic improvement with prednisolone
      and cholestyramine. Prompt treatment may improve the prognosis. In Japan,
      leflunomide has been implicated as a possible cause to initiate or exacerbate
      interstitial pneumonia in patients with RA according to postmarketing
      surveillance. Clinicians should exclude pulmonary disease prior to initiating
      leflunomide treatment in patients with RA on the basis of a thorough history and
      physical examination, and chest radiograph.

PMID- 15940780
TI  - Persistent cryoglobulinemic vasculitis following successful treatment of
      hepatitis C virus.
AB  - There is a well established link between type II mixed cryoglobulinemia (MC) and
      hepatitis C virus (HCV) infection, and HCV is believed to be the cause of
      cryoprotein formation and tissue deposition. Successful treatment of HCV
      infection has resulted in resolution of cryoglobulinemia and vasculitis. We
      describe 4 patients who had persistent MC and vasculitis despite successful
      eradication of HCV with antiviral therapy.

PMID- 15940781
TI  - Marked dilatation of pulmonary arteries in mixed connective tissue disease.

PMID- 15940783
TI  - [protein toxins and their medical applications].

PMID- 15940784
TI  - [Construction and expression of ricin A chain and green fluorescent protein
      fusion gene in E. coli].
AB  - OBJECTIVE: To study the expression and purification of a fusion protein of ricin
      A chain (RTA) and green fluorescent protein (GFP). METHODS: The DNA sequence
      encoding ricin A chain was inserted into pEGFPC1 first to make the template
      sequence of the fusion protein. The fusion gene was amplified from the plasmid
      pEGFP-RTA by PCR, and directly subcloned into T vector. The fusion gene then was
      cloned into expression vector pET-28a(+), and the sequence was confirmed by
      sequencing. Expression was induced by IPTG in E. coli BL21(DE3). The fusion
      protein was purified by metal chelated affinity chromatography. The cytotoxicity
      of fusion protein was analyzed by the MTT assay in HepG2 and Hela cells. RESULTS:
      The fusion protein of ricin A chain and GFP could be produced in E. coli
      transformed with the expression plasmid of pET-28a(+)-GFP-RTA. The molecular
      weight of the recombinant protein was measured by SDS-PAGE. The fusion protein
      showed a green fluorescence and had a similar cytotoxicity of RTA. CONCLUSION: A
      recombinant fusion protein of RTA and GFP expressed in E. coli is possessed of
      similar biological activity of individual GFP and RTA, which could be used in
      study of the intracellular trafficking and translocation of RTA.

PMID- 15940785
TI  - [Cloning and expression of luffin-a gene from the seeds of Luffa cylindrical].
AB  - OBJECTIVE: To clone luffin-a cDNA from the seeds of Luffa cylindrical, and to
      obtain bioactive recombinant luffin-a protein using the expression vector pET-44a
      (+) in E. coli. METHODS: The cDNA sequence encoding luffin-a was cloned from the
      fresh seeds of Luffa cylindrical by RT-PCR. The target DNA fragments were
      sequenced after T-A cloning. The luffin-a expression plasmid was constructed by
      inserting the luffin-a cDNA fragment into vector pET-44a (+). Luffin-a was
      expressed in E. coli by addition of IPTG into final concentration 1.0 mmol/L. The
      recombinant luffin-a was identified by SDS-PAGE. The biological activity of
      luffin-a protein was evaluated by using the MTT assay in HepG2 cells following
      fluid-phase endocytosis. RESULTS: In comparison with the reported luffin-a, the
      homology of nucleotide sequence of the cloned luffin-a gene was 99.73%, while
      their amino acid sequences were identical. The solubility of recombinant protein
      was analyzed by SDS-PAGE, and the luffin-a was mainly produced in inclusion
      bodies. The recombinant luffin-a, renatured by dialysis of the denatured
      products, showed a similar cytotoxicity to ricin A chain. CONCLUSION: The cDNA of
      luffin-a has been successfully cloned. The recombinant luffin-a protein expressed
      by E. coli is bioactive.

PMID- 15940786
TI  - [Study on lysosomes degradation of ricin A chain].
AB  - OBJECTIVE: To study lysosomes involvement in the degradation of ricin A chain.
      METHODS: A lysosome-targeted singal KFERQ was added to the C terminus of rRTA by
      DNA recombinant technology. A pKK223.3 expression system in E. coli was used to
      produce recombinant ricine A chain (rRTA) and rRTA-KFERQ. Recombinant proteins
      were purified by affinity chromatography using Blue-Sepharose 6B. The
      cytotoxicity of recombinant proteins was measured by the MTT method. RESULTS:
      Recombinant RTA-KFERQ was 49.87%, 54.18% and 88.68% less cytotoxic than RTA
      itself on the three cell lines HEPG2, Hela and A549, respectively. CONCLUSION:
      Lysosomes can degrade, but not completely inactivate RTA in different cells,
      suggesting cells may have other degradation pathways for RTA.

PMID- 15940787
TI  - [Purification and anti-cancer activity of ricin].
AB  - OBJECTIVE: To extract and purify ricin from castor beans and to evaluate its anti
      cancer activity. METHODS: Ricin was purified from castor beans according the
      modified method of Nicolson and Blaustin. The lectins were extracted in 0.01
      mol/L phosphate buffered saline and isolated in the 40% to 80% fraction of
      ammonium sulfate precipitation. The dialyzed fractionated preparation was applied
      with a Sepharose 4B column. The lectins were eluted with a linear lactose
      gradient (0.01 mol/L approximately 0.5 mol/L). Ricin was separated from the
      ricinus agglutinin by gel filtration on a Sephadex G-100. MTT was applied to
      analyze the cytotoxicity with different dosage of ricin in different cancer cell
      lines. RESULTS: There was no difference between the killing effect of normal
      cells and that of colon cancer cells by using the high dosage of ricin (5 x 10(
      8) mol/L approximately 5 x 10(-10) mol/L). However, the cytotoxicity was
      significant different in those cells with the low dosage of ricin (5 x 10(-11)
      mol/L approximately 5 x 10(-13) mol/L). Meanwhile ricin had the similar
      cytotoxicity to leukemia cell K562 and colon cancer cell SW480. CONCLUSION: Ricin
      is able to kill tumor cells selectively at low concentration, but the selectivity
      does not appear at high concentrations.

PMID- 15940788
TI  - [Expression of P53 and Bax in rat liver induced by microcystin LR in vivo].
AB  - OBJECTIVE: To examine the expression of P53, Bcl-2 and Bax proteins in rat liver
      after exposed to microcystin LR. METHODS: SD rats received microsystin LR by
      gastric perfusion. The expression of P53, Bax and Bcl-2 in liver was detected by
      Western blot. RESULTS: The expression of P53 and Bax in each treatment group
      increased significantly compared with that in control group(P<0.05), with the
      exception of 0.1 microg/kg LR exposure group. Moreover, with exposure levels
      increasing the expression of P53 and Bax increased gradually; while no changes of
      the expression of Bcl-2 were observed. CONCLUSION: P53 and Bax may play important
      roles in microcystin LR induced apoptosis, but Bcl-2 seems not be involved in
      this process.

PMID- 15940789
TI  - [Detection of cagA gene, CagA protein in Helicobacter pylori isolates and its
      antibody in serum of patients with gastric diseases by a recombinant protein CagA
      1].
AB  - OBJECTIVE: To construct a prokaryotic expression system of a fragment from
      Helicobacter pylori cagA gene and to detect the CagA positive Helicobacter pylori
      (CagA(+) H. pylori) and its antibody with the recombinant protein cagA 1.
      METHODS: H.pylori isolates were obtained from biopsy specimens of 156 patients
      with gastric diseases. PCR method was used to detect frequency of cagA gene in
      109 H. pylori isolates and to amplify a 2 148 bp fragment (cagA1) of cagA gene
      from a clinical strain Y06. A prokaryotic expression system of cagA1 was
      constructed. Expression of the target recombinant protein (rCagA1) was examined
      by SDS-PAGE. Western blot and immunodiffusion assay were applied to determine
      immunoreactivity and antigenicity of rCagA1. Two ELISA protocols were established
      to detect CagA expression in 109 H. pylori isolates and CagA antibody in serum of
      patients with gastric diseases. Correlations between infection of CagA(+) H.
      pylori and gastric diseases were analyzed. RESULTS: H. pylori strains were
      isolated from 80.8% of the biopsy specimens (126/156) and 97.2% of the isolates
      (106/109) were cagA gene positive. In comparison with the reported data,
      homologies of nucleotide and putative amino acid sequences of the cloned cagA1
      fragment were 94.83% and 93.30%, respectively. The output of rCagA1 was
      approximate 30.0% of the total bacterial proteins. rCagA1 was able to combine
      with the commercial antibody against whole cell of H. pylori and to induce the
      immunized rabbits to produce antibody with an immunodiffusion titer of 1:4. 92.6%
      of the H. pylori isolates (101/109) expressed CagA and 88.1% of serum samples
      (96/109) were CagA antibody positive. The percentage of CagA(+) H. pylori strains
      (97.9%) of peptic ulcer trended to be higher than that of gastritis (88.5%), but
      there was no statistically significant difference between two groups
      (chi(2)=3.48, P>0.05). CONCLUSION: The recombinant rCagA1 can be used to detect
      CagA of H. pylori and its antibody. No association is found between CagA
      expression of H. pylori strains and types of gastric diseases in this study.

PMID- 15940790
TI  - [Junctional epithelialization of dental implants in animals].
AB  - OBJECTIVE: To detect the histological changes and the expression of proliferating
      cell nuclear antigen (PCNA) in junctional epithelialization of dental implants.
      METHODS: The junctional epithelium was detected by HE staining and the PCNA
      expression was observed by immunohistochemical staining on the st, 3rd, 6th, 9th,
      12th, 15th, 20th and 30th day after implantation in Beagle dogs. RESULTS: The
      junctional epithelium began to form and PCNA was expressed positively 12 days
      after implantation. The epithelial hyperplasia tended to stabilization and the
      expression of PCNA weakened drastically 15 days after implantation. The
      epithelial attachment showed to be similar to that of natural teeth 20 days
      later. CONCLUSION: The gingiva epithelium can attach to titanium implants forming
      junctional epithelium which is similar to the natural teeth.

PMID- 15940791
TI  - [Tissue engineered bone reconstruction with modified PLGA/Type-I collagen
      compound scaffold].
AB  - OBJECTIVE: To fabricate bone grafts by bone marrow stromal cell combined with
      modified PLGA/Type-I collagen compound scaffold using tissue engineering method.
      METHODS: The modified PLGA/Type-I collagen compound scaffold was fabricated. The
      rabbit primary cultured osteoblasts were identified and seeded onto the modified
      compound scaffold for one week in vitro. The adhesion and growth of cells were
      observed with scanning electron microscope. The complex of cells and scaffold was
      implanted into the subcutaneous region of rabbits and new bone formation was
      evaluated. RESULTS: The rabbit bone marrow stromal cells were induced and
      differentiated into osteoblasts. The adhesion and growth of osteoblasts in
      cluster were observed on the surface of scaffolds. New bone formation was
      observed at one month postoperatively and active osteoblasts were found on the
      surface of the newly formed bone in vivo. CONCLUSION: The complex of PLGA and
      type-I collagen is an appropriate biodegradable scaffold and can be applied in
      bone tissue engineering.

PMID- 15940793
TI  - [Ultrastructure and crystallin mutant molecular modeling of hereditary
      coralliform cataract].
AB  - OBJECTIVE: To observe the correlation of gammaD-crystallin P23T mutant with lens
      ultrastructure of the hereditary coralliform cataract. METHODS: Complete
      ophthalmologic examinations were performed before lens extraction and lens
      samples were studied by transmission and scanning electric microscope
      respectively. Protein molecular modeling was performed using SWISS-MODEL(version
      2.0). RESULTS: Protein structure modeling demonstrated that the mutant caused a
      decrease in molecular final total energy and changes in the surface structure of
      gammaD-crystallin. Ultrastructure study revealed crystals deposited in lens,
      extensive granules dispersed in uncommon oval structure and the disorganization
      of lens epithelial cells. CONCLUSION: It is possible that the gammaD-crystallin
      P23T mutant is associated with abnormal crystals in lens and disorganization of
      lens epithelial cells.

PMID- 15940792
TI  - [Pathophysiology of bleomycin-induced pulmonary hypertension in immature
      rabbits].
AB  - OBJECTIVE: To investigate the evolution of pulmonary hypertension induced by
      intratracheal bleomycin (BLM) in immature rabbits. METHODS: Immature rabbits were
      divided into control and BLM groups. Two and four weeks after intratracheal
      normal saline or BLM, the systolic, diastolic and mean pulmonary artery pressure
      (PASP, PADP, MPAP) were measured by micro-catheter, the pathological changes and
      the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary
      arteries were evaluated by HE and in situ hybridization. RESULTS: Pulmonary
      artery pressure was elevated 2 weeks and 4 weeks after intratracheal BLM. Two
      weeks after treatment PASP was (16.5 +/- 2.9 compared with 25.2 +/- 7.0) mmHg,
      PADP (8.8 +/- 4.2 compared with 13.1 +/- 3.8) mmHg, MPAP (12.1 +/-4.0 compared
      with 18.4 +/-4.7) mmHg in control and BLM groups, respectively; meanwhile 4 weeks
      after treatment, PASP was (16.7 +/-2.3 compared with 23.8 +/-7.1) mmHg, PADP (7.3
      +/-1.5 compared with 13.8 +/-6.6) mmHg, MPAP (11.3 +/- 1.9 compared with 17.6 +/-
      6.3) mmHg in control and BLM groups, respectively. The thickness of arterial wall
      increased and the cavity became narrow, and the thickness index (TI) and area
      index (AI) increased in middle and small pulmonary arteries 2 weeks and 4 weeks
      after intratracheal BLM. Two weeks after treatment TI was 0.52 +/- 0.16 compared
      with 0.65 +/- 0.16, AI 0.74+/- 0.17 compared with 0.84 +/- 0.14 in control and
      BLM groups, respectively; meanwhile 4 weeks after treatment TI was 0.52 +/- 0.11
      compared with 0.64 +/- 0.15, AI 0.71 +/- 0.15 compared with 0.85 +/- 0.10 in
      control and BLM groups. The levels of VEGFmRNA and eNOSmRNA expression in
      pulmonary arterial endothelial cells decreased 2 weeks and 4 weeks after
      intratracheal BLM. Two weeks after treatment VEGFmRNA was 0.83 +/- 0.09 compared
      with 0.45 +/- 0.11, eNOSmRNA 0.79 +/- 0.12 compared with 0.45 +/- 0.12 in control
      and BLM groups, respectively; meanwhile 4 weeks after VEGFmRNA was 0.81 +/- 0.19
      compared with 0.46 +/- 0.15, eNOSmRNA 0.89 +/- 0.14 compared with 0.44 +/- 0.12
      in control and BLM groups, respectively. CONCLUSION: Intratracheal bleomycin may
      induce the pathological changes of pulmonary arteries and decrease the expression
      of VEGFmRNA and eNOSmRNA in immature rabbits, which results in pulmonary
      hypertension.

PMID- 15940794
TI  - [Application of DHPLC in human genomic SNP screening and genotyping for all-trans
      retinol dehydrogenase].
AB  - OBJECTIVE: To assess the efficacy of denaturing high-performance liquid
      chromatography (DHPLC) as a new screening assay for sequence variation in SNP
      detecting and new approach to SNP genotyping. METHODS: DHPLC was used to screen
      SNPs in 8 DNA pools each consisting of DNA from 5 individuals, and genotype the
      identified SNPs in 150 Chinese subjects from Hong Kong. RESULTS: Seventeen SNPs
      were identified: 12 were novel and 5 were previously reported; 11 were found in
      screening stage and the other 6 were found in genotyping stage; 2 were only found
      in Caucasian samples; 3 showed ethnic difference of minor allele frequency(MAF);
      7 were common with the MAF>0.05 in Chinese samples. CONCLUSION: The results
      demonstrated the efficiency of DHPLC in screening SNPs when coupled with DNA
      pooling strategy, and in genotyping SNPs.

PMID- 15940795
TI  - [Exclusion of the association of five known mutations with congenital stationary
      nyctalopia in a large Chinese family].
AB  - OBJECTIVE: To detect gene mutations associated with autosomal dominant congenital
      stationary night blindness(ADCSNB) in a large Chinese family. METHODS: Genomic
      DNAs were extracted from peripheral blood samples of 16 affected and 14
      unaffected family members. According to 5 missense mutations in 3 genes reported
      previously, 4 pairs of primers were designed and corresponding exons containing
      the five mutation sites were amplified by polymerase chain reaction. Amplified
      products were purified and sequenced by MegaBACE1000 capillary array
      electrophoresis DNA sequencer. Full field electroretinogram (ERG, ISCEV) of
      patients was recorded and analyzed by Roland Consult System. RESULTS: Dark
      adapted ERG showed a-wave was normal, but b-wave of the patients was markedly
      decreased. None of the five missense mutations were detected in 16 affected and
      14 unaffected family members. CONCLUSION: The molecular pathogenesis of ADCSNB in
      this family does not involve point mutations or deletions of these five sites,
      which indicates the heterogeneity of ADCSNB.

PMID- 15940796
TI  - [Determination of interleukine-16 levels in peritoneal fluid and serum of women
      with endometriosis].
AB  - OBJECTIVE: To investigate the role of interleukine-16 (IL-16) in the pathogenesis
      of endometriosis. METHODS: Enzyme-linked immunosorbent assay (ELISA) was used to
      determine the levels of IL-16 in peritoneal fluid and serum specimens of 22 women
      with different stage endometriosis and 22 controls. RESULTS: The median levels of
      IL-16 in peritoneal fluid and serum were 290.5 pg/ml and 539.4 pg/ml in women
      with endometriosis, and 296.6 pg/ml and 778.1 pg/ml in controls, respectively;
      there was no significant difference between two groups (P>0.05). However, the IL
      16 levels in peritoneal fluid and serum of patients with minimal/mild stage
      endometriosis and controls were all significantly higher than those of patients
      with moderate/severe endometriosis (P<0.01, <0.05). In addition, there was no
      statistical correlation of peritoneal IL-16 levels with those in serum (P>0.05).
      CONCLUSION: Reduced levels of IL-16 in peritoneal fluid and serum of women with
      advanced stage endometriosis may imply a role of IL-16 in the development and
      progression of endometriosis.

PMID- 15940797
TI  - [Clinical value of three-dimensional dynamic contrast-enhanced MR angiography in
      diagnosis of angiostenosis after liver transplantation].
AB  - OBJECTIVE: To evaluate the clinical application of three-dimensional dynamic
      contrast-enhanced MR angiography (3D DCE MRA) in diagnosis of angiostenosis after
      liver transplantation. METHODS: Twenty recipients of liver transplantation
      underwent 3D DCE MRA examination. The blood vessel rating grades were accessed
      and the relative diameter of vascular anastomosis was measured; and the results
      were compared with those of US or DSA examination. RESULTS: Satisfactory
      angiography images were obtained in all cases by 3D DCE MRA, including 11 cases
      with normal and mild stenosis, 5 with moderate and 4 with severe stenosis in
      hepatic artery. Except one case in which 3D DCE MRA showed severe stenosis but
      DSA showed moderate stenosis, the results of MRA were all consistent with those
      of US or/and DSA in the stenosis degree of the portal vein, hepatic vein and the
      postcava. CONCLUSION: 3D DCE MRA is an effective technique to evaluate the degree
      of angiostenosis after liver transplantation.

PMID- 15940798
TI  - [Low initial dose of levothyroxine for treatment of congenital hypothyroidism].
AB  - OBJECTIVE: To evaluate the results of treatment of infants with congenital
      hypothyroidism (CH) with a low initial dosage of levothyroxine. METHODS: 138
      newborns with primary CH detected by neonatal screening were divided into 3
      groups according to levels of serum TSH, TT(3) and TT(4): sub-clinical CH (TSH
      >50 mU/L), mild CH (TT(4) <54 nmol/L), severe CH (TT(4)<54 nmol/L and TT(3)<1.2
      nmol/L). The initial dose of levothyroxine was (3.5 +/-1.0) microg/(kg.d) for sub
      clinical CH group, (4.3 +/-0.7)microg/(kg.d) for mild CH group and (4.7 +/-
      0.6)microg/(kg.d) for severe CH group. Follow-up evaluation was carried out at 1,
      2 and 3 months of age by measuring serum levels of TT(3), TT(4) and TSH. The
      time, when clinical signs and symptoms were eliminated and serum levels of TT(3),
      TT(4) and TSH normalized, was recorded. Development Quotient (DQ) testing was
      performed when CH cases were about 2 years old. RESULTS: The mean initial dose of
      levothyroxine in 138 cases was (4.3 +/-0.9)microg/(kg.d). In one month the serum
      TT(3) and TT(4) levels returned to normal, while for TSH levels 67.4 % cases
      reached normal range in 2 months and 84.1 % in 3 months. Two months after
      therapy, the levels of TT(3) and TT(4) reached to the upper half of normal range
      and there were no signs or symptoms of hypothyroidism. The time for all cases in
      3 groups to reach the normal clinical and biochemical indicators was similar
      (P=0.925). The dosage for cases with low circulating thyroxine before treatment
      was higher than that of the other groups (P<0.01). The average DQ score of 18
      cases after treatment was 116.7 +/- 17.0. CONCLUSION: he levothyroxine dosage of
      (4.3 +/- 0.9)microg/(kg.d) is appropriate for the initial treatment of the
      majority of infants with CH. However it is better to individualize the dosage for
      each case.

PMID- 15940799
TI  - [Establishment of a heterotopic heart transplantation model in mice].
AB  - OBJECTIVE: To establish a mouse model of heterotopic heart transplantation.
      METHODS: In isotransplantation,BALB/c mice were used as both donors and
      recipients. In allotransplantation, C57 mice were used as donors and BALB/c mice
      as recipients. The hearts of donor mice were transplanted into the abdominal
      cavity of recipient mice, connecting aortic ascent artery of donor mice and
      abdominal aortic artery of recipient mice, main pulmonary artery of donor mice
      and inferior vena cava of recipient mice. RESULTS: The mouse model of heterotopic
      heart transplantation was established successfully with a success rate of 90 %.
      The mean time of hot ischemia and cold ischemia were (0.9 +/-0.05) min and (34.8
      +/-0.7) min, respectively. The survival time of isograft was more than 100 days
      and that of allograft was (7.7 +/- 0.3) days. CONCLUSION: The operational
      procedure of donor heart and the quality of blood vessel anastomosis are two key
      points for successful heterotopic heart transplantation.

PMID- 15940800
TI  - [Transperitoneal laparoscopic ligation of renal lymphatic vessels for treatment].

PMID- 15940801
TI  - [Analysis of sonographic misdiagnosis for ovarian mature teratoma].

PMID- 15940802
TI  - [Application of fiberoptic bronchoscopic intubation in difficult airway of
      maxillofacial surgery].

PMID- 15940803
TI  - [DNA methyltransferases and early embryo development].

PMID- 15940804
TI  - Conflict questions. Insurance execs on healthcare boards prompts worry.

PMID- 15940805
TI  - DWP incapacity adjudicators seem to work on the assumption that 'doctor knows
      best'.

PMID- 15940806
TI  - Dietary approaches to treatment could have a major public health impact.

PMID- 15940807
TI  - Fecal incontinence: what to know about this often-hidden problem.

PMID- 15940808
TI  - Investigating chorion softening of zebrafish embryos with a microrobotic force
      sensing system.
AB  - The zebrafish is a model organism for addressing questions of vertebrate embryo
      development. In this paper, the softening phenomenon of the chorion envelope of
      zebrafish embryos at different developmental stages was mechanically quantitated
      by using a microrobotic force sensing system. The microrobotic system integrates
      a piezoelectric cellular force sensor to measure the required forces for
      penetrating the chorion envelope. Magnitude of penetration forces was found to
      decrease as an embryo develops. The results mechanically quantitate "chorion
      softening" in zebrafish embryos due to protease activities subtly modifying the
      chorion structure, providing an understanding of zebrafish embryo development.

PMID- 15940809
TI  - A bedtime story: by Caveman.

PMID- 15940811
TI  - Health is the loser in the vote against Europe.

PMID- 15940810
TI  - Harry Goldblatt and the discovery of renin.
AB  - In 1934, pathologist Harry Goldblatt established the first animal model of
      hypertension. This model provided researchers with the tools to delineate the
      renin-angiotensin system of blood pressure control and, eventually, to design
      enzyme inhibitors for the treatment of chronic hypertension.

PMID- 15940812
TI  - An AIDS patient with fever and rash.

PMID- 15940813
TI  - Countering the difficult aspects of ageing.

PMID- 15940814
TI  - Stem cell research: hope and hype.

PMID- 15940815
TI  - Research scandal forces Israel to tighten up supervision.

PMID- 15940816
TI  - Court case shines spotlight on South African AIDS policy.

PMID- 15940817
TI  - Donor charged in Romania's first organ trafficking trial.

PMID- 15940818
TI  - Evaluation of a real-time quantitative polymerase chain reaction assay for
      detection and quantitation of virulent Rhodococcus equi.
AB  - OBJECTIVE: To evaluate a real-time quantitative polymerase chain reaction (QPCR)
      assay in the detection and quantitation of virulent Rhodococcus equi. SAMPLE
      POPULATION: 1 virulent, 2 intermediately virulent, and 2 avirulent strains of R.
      equi and 16 isolates of bacteria genetically related to R. equi. PROCEDURE: The
      QPCR assay was evaluated for detection and quantitation of the virulence
      associated gene (vapA) of R. equi in pure culture and in samples of
      tracheobronchial fluid, which were inoculated with known numbers of virulent R.
      equi. Results were compared with those derived via quantitative microbial culture
      and standard polymerase chain reaction methods. RESULTS: The QPCR assay detected
      the vapA gene in pure culture of R. equi and in tracheobronchial fluid samples
      that contained as few as 20 CFUs of virulent R. equi/mL and accurately
      quantitated virulent R. equi to 10(3) CFUs/mL of fluid. The assay was highly
      specific for detection of the vapA gene of virulent R. equi and was more
      sensitive than standard polymerase chain reaction for detection of R. equi in
      tracheobronchial fluid. CONCLUSIONS AND CLINICAL RELEVANCE: The QPCR assay
      appears to be a rapid and reliable method for detecting and quantitating virulent
      R. equi. The accuracy of the QPCR assay is comparable to that of quantitative
      microbial culture. The increased sensitivity of the QPCR method in detection of
      virulent R. equi should facilitate rapid and accurate diagnosis of R. equi
      pneumonia in foals.

PMID- 15940819
TI  - Recent developments in the field of monolithic stationary phases for capillary
      electrochromatography.
AB  - This review summarizes the contributions to the rapidly growing area of
      monolithic columns based on both silica and synthetic polymers for capillary
      electrochromatography and chip electrochromatography, with a focus on those
      published during the year 2004. A wide variety of both modified approaches to the
      "old" monoliths and new monoliths have been reported despite the very short
      period of time covered. This demonstrates that monolithic stationary phases have
      become a well-established format in the field of electrochromatography. The
      simplicity of their preparation as well as the good control over their porous
      properties and surface chemistries make the monolithic separation media an
      attractive alternative to capillary columns packed with particulate materials.

PMID- 15940820
TI  - Tick immunobiology.
AB  - Ticks are of vast medical and veterinary public health importance due to direct
      damage caused by feeding and their roles in transmitting well known and emerging
      infectious agents. Ticks and tick-borne pathogens stimulate the immune system of
      the host. Those immune interactions are of importance in tick biology, pathogen
      transmission and control of ticks and tick-borne diseases. Both innate and
      specific acquired immune defenses are involved in the responses of vertebrate
      hosts to infestation. Ticks have evolved countermeasures to circumvent host
      immune defenses. This review addresses the immunobiology of the tick-host
      interface from the perspectives of the pharmacology of tick saliva; relationship
      of tick saliva to pathogen transmission; host immune responses to infestation;
      tick modulation of host immune defences; and genomic/proteomic strategies for
      studying tick salivary gland molecules.

PMID- 15940821
TI  - Emerging tick-borne infections: rediscovered and better characterized, or truly
      'new' ?
AB  - The emergence of Lyme borreliosis as a public health burden within the last two
      decades has stimulated renewed interest in tick-borne infections. This attention
      towards ticks, coupled with advances in detection technologies, has promoted the
      recognition of diverse emergent or potentially emerging infections, such as
      monocytic and granulocytic ehrlichiosis, local variants of spotted fever group
      rickettsioses, WA-1 babesiosis, or a Lyme disease mimic (Masters' Disease). The
      distribution of pathogens associated with well-described tick-borne zoonoses such
      as human babesiosis due to Babesia microti or B. divergens seems wider than
      previously thought. Bartonellae, previously known to be maintained by fleas, lice
      or sandflies, have been detected within ticks. Purported 'new' agents, mainly
      identified by sequencing of PCR products and comparison with those sequences
      present in GenBank, are being increasingly reported from ticks. We briefly review
      the diversity of these infectious agents, identify aetiological enigmas that
      remain to be solved, and provide a reminder about 'old friends' that should not
      be forgotten in our pursuit of novelty. We suggest that newly recognised agents
      or tick/pathogen associations receive careful scrutiny before being declared as
      potential public health burdens.

PMID- 15940822
TI  - Simultaneous modelling of survival and longitudinal data with an application to
      repeated quality of life measures.
AB  - In biomedical studies, interest often focuses on the relationship between
      patient's characteristics or some risk factors and both quality of life and
      survival time of subjects under study. In this paper, we propose a simultaneous
      modelling of both quality of life and survival time using the observed
      covariates. Moreover, random effects are introduced into the simultaneous models
      to account for dependence between quality of life and survival time due to
      unobserved factors. EM algorithms are used to derive the point estimates for the
      parameters in the proposed model and profile likelihood function is used to
      estimate their variances. The asymptotic properties are established for our
      proposed estimators. Finally, simulation studies are conducted to examine the
      finite-sample properties of the proposed estimators and a liver transplantation
      data set is analyzed to illustrate our approaches.

PMID- 15940823
TI  - A diagnostic for association in bivariate survival models.
AB  - We propose exploratory, easily implemented methods for diagnosing the
      appropriateness of an underlying copula model for bivariate failure time data,
      allowing censoring in either or both failure times. It is found that the proposed
      approach effectively distinguishes gamma from positive stable copula models when
      the sample is moderately large or the association is strong. Data from the
      Women's Health and Aging Study (WHAS, Guralnik et al., The Womens's Health and
      Aging Study: Health and Social Characterisitics of Older Women with Disability.
      National Institute on Aging: Bethesda, Mayland, 1995) are analyzed to demonstrate
      the proposed diagnostic methodology. The positive stable model gives a better
      overall fit to these data than the gamma frailty model, but it tends to
      underestimate association at the later time points. The finding is consistent
      with recent theory differentiating 'catastrophic' from 'progressive' disability
      onset in older adults. The proposed methods supply an interpretable quantity for
      copula diagnosis. We hope that they will usefully inform practitioners as to the
      reasonableness of their modeling choices.

PMID- 15940824
TI  - Abstracts of the IXth Congress of the Middle East Society for Organ
      Transplantation (MESOT). December 6-10, 2004, Ankara, Turkey.

PMID- 15940825
TI  - Researchers develop portable device that can instantly detect heart and gum
      disease.

PMID- 15940826
TI  - Habitat selection and ecological speciation in Galapagos warbler finches
      (Certhidea olivacea and Certhidea fusca).
AB  - We investigated phylogeographic divergence among populations of Galapagos warble
      finches. Their broad distribution, lack of phenotypic differentiation and low
      levels of genetic divergence make warbler finches an appropriate model to study
      speciation in allopatry. A positive relationship between genetic and geographical
      distance is expected for island taxa. Warbler finches actually showed a negative
      isolation by distance relationship, causing us to reject the hypothesis of
      distance-limited dispersal. An alternative hypothesis, that dispersal is limited
      by habitat similarity, was supported. We found a positive correlation between
      genetic distances and differences in maximum elevation among islands, which is an
      indicator of ecological similarity. MtDNA sequence variation revealed
      monophyletic support for two distinct species. Certhidea olivacea have recently
      dispersed among larger central islands, while some Certhidea fusca have recently
      dispersed to small islands at opposite ends of the archipelago. We conclude that
      females have chosen to breed on islands with habitats similar to their natal
      environment. Habitat selection is implicated as an important component of
      speciation of warbler finches, which is the earliest known divergence of the
      adaptive radiation of Darwin's finches. These results suggest that small
      populations can harbour cryptic but biologically meaningful variation that may
      affect longer term evolutionary processes.

PMID- 15940827
TI  - Laparoscopic ligation of the median sacral artery before excision of type I
      sacrococcygeal teratomas.

PMID- 15940828
TI  - Comment on Doctor Swenson's paper on Hirschsprung's disease.

PMID- 15940830
TI  - [Abstracts of the XLI Congress of the Brazilian Society of Tropical Medicine. 6
      10 March 2005, Florianopolis, Brazil].

PMID- 15940829
TI  - Abstracts of the 13th Annual Meeting of the Israel Society for Neuroscience.
      Eilat, Israel, November 28-30, 2004.

PMID- 15940831
TI  - Abstracts of the 53rd Annual Meeting of the Pacific Coast Reproductive Society.
      May 4-8, 2005, Indian Wells, California, USA.

PMID- 15940832
TI  - Abstracts of the Associate Professional Sleep Societies, LLC 19th Annual Meeting.
      June 18-23, 2005, Denver, Colorado, USA.

PMID- 15940834
TI  - Clinical Research 2005 Abstracts.

PMID- 15940833
TI  - 2005 Combined Annual Meeting of the Central Society for Clinical Research and the
      American Federation for Medical Research midwestern section (CSCR-MWAFMR).
      Abstracts.

PMID- 15940835
TI  - [Abstracts of the 46th National Congress of the Italian Society of Nephrology.
      Montesilvano, Italy, 4-7 May 2005].

PMID- 15940836
TI  - Hospital admission x-rays. 1955.

PMID- 15940837
TI  - Enhanced surveillance for vaccine-associated adverse events: dTap catch-up of
      high school students in Yukon.

PMID- 15940838
TI  - Active hospital-based surveillance for meningococcal polysaccharide vaccine
      adverse events after an emergency mass immunization program, Edmonton, Alberta.

PMID- 15940840
TI  - Avian influenza, Vietnam--update.

PMID- 15940839
TI  - 50 years ago. March 1955 Report of the Commission to study the establishment of
      medical, dental and veterinary colleges on a New England regional basis.

PMID- 15940841
TI  - Update on rabies vaccines. An advisory committee statement.

PMID- 15940842
TI  - Fate of disinfection by-products in groundwater during aquifer storage and
      recovery with reclaimed water.
AB  - Knowledge on the behaviour of disinfection by-products (DBPs) during aquifer
      storage and recovery (ASR) is limited even though this can be an important
      consideration where recovered waters are used for potable purposes. A reclaimed
      water ASR trial in an anoxic aquifer in South Australia has provided some of the
      first quantitative information at field-scale on the fate and transport of
      trihalomethanes (THMs) and haloacetic acids (HAAs). The results revealed that THM
      half-lives varied from <1 to 65 days, with persistence of chloroform being
      highest and bromoform lowest. HAA attenuation was rapid (<1 day). Rates of THM
      attenuation were shown to be highly dependent on the geochemical environment as
      evidenced by the 2-5 fold reduction in half-lives at the ASR well which became
      methanogenic during the storage phase of the trial, as compared to an observation
      well situated 4 m away, which remained nitrate-reducing. These findings agree
      with previous laboratory-based studies which also show persistence declining with
      increased bromination of THMs and reducing redox conditions. Modelling suggests
      that the chlorinated injectant has sufficient residual chlorine and natural
      organic matter for substantial increases in THMs to occur within the aquifer,
      however this is masked in some of the field observations due to concurrent
      attenuation, particularly for the more rapidly attenuated brominated compounds.
      The model is based on data taken from water distribution systems and may not be
      representative for ASR since bromide and ammonia concentrations in the injected
      water and the possible role of organic carbon in the aquifer were not taken into
      consideration. During the storage phase DBP formation potentials were reduced as
      a result of the removal of precursor material despite an increase in the THM
      formation potential per unit weight of total organic carbon. This suggests that
      water quality improvements with respect to THMs and HAAs can be achieved through
      ASR in anoxic aquifers.

PMID- 15940843
TI  - Gene expression profiling for managing breast cancer treatment.

PMID- 15940844
TI  - Contrast-enhanced cardiac computed tomographic angiography for coronary artery
      evaluation.

PMID- 15940845
TI  - Valuing life: a plea for disaggregation.
AB  - Each government agency uses a uniform figure to measure the value of a
      statistical life (VSL). This is a serious mistake. The very theory that underlies
      current practice calls for far more individuation of the relevant values.
      According to that theory, VSL should vary across risks. More controversially, VSL
      should vary across individuals -- even or especially if the result would be to
      produce a lower number for some people than for others. One practical implication
      is that a higher value should be given to programs that reduce cancer risks.
      Another is that government should use a higher VSL for programs that
      disproportionately benefit the wealthy -- and a lower VSL for programs that
      disproportionately benefit the poor. But there are two serious complications
      here. First, bounded rationality raises problems for the use of private
      willingness to pay, which underlies current calculations of VSL. Second, the
      beneficiaries of regulation sometimes pay only a fraction or even none of its
      cost; when this is so, the appropriate VSL for poor people might be higher, on
      distributional grounds, than market evidence suggests. An understanding of this
      point has implications for foundational issues about government regulation,
      including valuation of persons in poor and wealthy nations.

PMID- 15940846
TI  - Rehabilitating bioethics: recontextualizing in vitro fertilization outside
      contractual autonomy.

PMID- 15940847
TI  - Efficacy of chloroquine, amodiaquine, sulfadoxine-pyrimethamine, chloroquine
      sulfadoxine-pyrimethamine combination, and amodiaquine-sulfadoxine-pyrimethamine
      combination in Central African children with noncomplicated malaria.
AB  - This paper reports a two-phase study in Bangui, Central African Republic (CAR):
      first, we assessed the clinical efficacy to chloroquine (CQ), sulfadoxine
      pyrimethamine (SP), and amodiaquine (AQ), then we tested the efficacy of two
      combinations: CQ + SP and AQ + SP. We used the standard 14-day WHO 2001 protocol
      to compare therapeutic responses in children under 5 years of age with acute
      uncomplicated Plasmodium falciparum malaria in Bangui between February 2002 and
      March 2004. The overall treatment failure rates with CQ, AQ, SP, CQ + SP, and AQ
      + SP were 40.9%, 20.0%, 22.8%, 7.2%, and 0%. These findings suggest that the
      Ministry of Health should recommend an interim policy with AQ + SP combination as
      the first-line antimalarial drug in Bangui until best alternative treatments like
      artemisinin-based combination therapies (ACTs) become available at low prices in
      the CAR.

PMID- 15940848
TI  - [Intracranial neuroendocrine carcinoma: report of one case].

PMID- 15940849
TI  - Endothelial tight junctions form the blood-brain barrier.

PMID- 15940850
TI  - Defining gap junctions.

PMID- 15940851
TI  - Lessons from expanded government enforcement efforts against drug companies.

PMID- 15940852
TI  - Perception and process at the Food and Drug Administration: obligations and trade
      offs in rules and guidances.

PMID- 15940853
TI  - Takings issues in the approval of generic biologics.

PMID- 15940854
TI  - Medical research on humans: regulation in Switzerland, the European Union, and
      the United States.

PMID- 15940855
TI  - The World Health Organization's prequalification program and its potential effect
      on data exclusivity laws.

PMID- 15940856
TI  - Gene therapy is facing a crucial hearing.

PMID- 15940857
TI  - In Vermont, a bid to legalize physician-assisted suicide.

PMID- 15940858
TI  - Illinois pharmacies ordered to provide birth control.

PMID- 15940859
TI  - Vast abuses cited at National Health Institutes.

PMID- 15940860
TI  - New attention for 2002 law on survivors of abortions.

PMID- 15940861
TI  - Evidence in Vioxx suits shows intervention by Merck officials.

PMID- 15940862
TI  - Bioethics panel suggests stem cell alternatives.

PMID- 15940863
TI  - Chimeras on the horizon, but don't expect centaurs.

PMID- 15940864
TI  - Florida halts fight to bar girl's abortion: after resisting, Governor Bush says
      state will abide by ruling.

PMID- 15940865
TI  - The line between life and death.

PMID- 15940866
TI  - Parthenolide and abscisic acid synthesis in feverfew are associated but
      environmental factors affect them dissimilarly.
AB  - The effect of harvest time, shading prior to harvest and water stress on
      parthenolide (PRT) concentration in feverfew and its possible connection with the
      abscisic acid (ABA) pathway were investigated. In plants harvested at different
      times of the day, acetumar the PRT levels were highest during late afternoon
      while ABA levels were greatest during morning hours. Shading plants during the
      afternoon prior to harvest caused a two-fold increase in ABA and no significant
      difference in PRT levels. ABA was higher in water-stressed plants while
      PRTcontent increased in plants following recovery from a water stress event. ABA
      inhibitors, norflurazon, sodium tungstate, naproxen and sodium bisulfite, were
      used to determine the connection between the biosynthesis of PRTand ABA.
      Norflurazon and naproxen reduced PRT concentration in cut flowers and in 2-month
      old plants. Sodium bisulfite and sodium tungstate reduced PRT only in cut
      flowers. Application of 2,4-D, a promoter of ABA synthesis, to potted plants
      resulted in a 2.5 fold increase in PRT levels. The inhibition of PRT formation in
      response to ABA inhibitors and the increase in PRT concentration observed with
      2,4-D application indicated that PRT is derived from carotenoid synthesis
      similarly to ABA and not directly from farnesyl pyrosphosphate (FPP) as suggested
      for other sesquiterpene Lactones. However, PRT and ABA levels are affected
      dissimilarly by environmental conditions. The overall results of the study
      indicated that simple agricultural practices, such as harvesting during afternoon
      and subjecting plants to a single water stress event, can increase PRT
      concentration in the final feverfew product with no additional costs of
      production prior to harvest.

PMID- 15940867
TI  - Jasmonates are essential factors inducing gummosis in tulips: mode of action of
      jasmonates focusing on sugar metabolism.
AB  - The purpose of this study was to know the mechanism of jasmonates to induce
      gummosis in tulip (Tulipa gesneriana L. cv. Apeldoorn) shoots, especially on the
      focus of sugar metabolism. Gummosis in the first internode of tulip plants was
      induced by the application of methyl jasmonate (JA-Me, 1% w/w in lanolin) and
      jasmonic acid (JA, 1% w/w in lanolin) 5 days after application and strongly
      stimulated by the simultaneous application of ethylene-releasing compound,
      ethephon (2-chloroethylphosphonic acid, 1% w/w in lanolin), although ethephon
      alone had little effect. JA-Me stimulated ethylene production of the first
      internodes of tulips, ethylene production increasing up to more than 5 times at
      day 1 and day 3 after the application. On the other hand, application of ethephon
      did not increase endogenous levels of jasmonates in tulip stems. Analysis of
      composition of tulip gums revealed that they were consisted of
      glucuronoarabinoxylan with an average molecular weight of ca. 700 kDa. JA-Me
      strongly decreased the total amount of soluble sugars in tulip stems even in 1
      day after application, being ca. 50% of initial values 5 days after application,
      but ethephon did not. However, both JA-Me and ethephon had almost no effect on
      the neutral sugar compositions of soluble sugars mainly consisting of glucose,
      mannose and xylose in ratio of 20:2:1 and traces of arabinose. Both JA-Me and
      ethephon applied exogenously stimulated senescence of tulip shoots shown by the
      loss of chlorophyll. These results strongly suggest that the essential factor of
      gummosis in tulips is jasmonates affecting the sugar metabolism in tulip shoots.
      The mode of action of jasmonates to induce gummosis of tulip shoots is discussed
      in relation to ethylene production, sugar metabolism and senescence.

PMID- 15940868
TI  - Cytokinin inhibits lateral root initiation but stimulates lateral root elongation
      in rice (Oryza sativa).
AB  - Research in lateral root (LR) development mainly focuses on the role of auxin.
      This article reports the effect of cytokinins (kinetin and trans-zeatin) on LR
      formation in rice (Oryza sativa L.). Our results showed that cytokinin has an
      inhibitory effect on LR initiation and stimulatory effect on LR elongation. Both
      KIN and ZEA at a concentration of 1 microM and above completely inhibited lateral
      root primordium (LRP) formation. The inhibitory effect of cytokinin on LR
      initiation required a continuous presence of KIN or ZEA in the growth solution.
      Cytokinin did not show any inhibitory effect on LR emergence from the seminal
      root once LRPs had been formed. The LRPs that developed in cytokinin-free
      solution can emerge normally in the solution containing inhibitory concentration
      (1 microM) of KIN and ZEA. The KIN and ZEA treatment dramatically stimulated LR
      elongation at all the concentrations tested. Maximum LR elongation was observed
      at a concentration of 0.01 microM KIN and 0.001 microM ZEA. The epidermal cell
      length increased significantly in LRs of cytokinin treated seedlings compared to
      those of untreated control. This result indicates that the stimulation of LR
      elongation by cytokinin is due to increased cell length. Exogenously applied
      auxin counteracted the effect of cytokinin on LR initiation and LR elongation,
      suggesting that cytokinin acts on LR elongation through an auxin dependent
      pathway.

PMID- 15940869
TI  - Carotenoid composition and its chemotaxonomic significance in leaves of ten
      species of the genus Ceratozamia (Cycads).
AB  - The qualitative composition and localization of carotenoids in leaflets of ten
      species of the genus Ceratozamia (Cycads) was investigated, and the distributions
      of 16 of these carotenoids, which were isolated and differently located in the
      chloroplast, are discussed. Eight classic carotenoids are located in the
      thylakoidal membranes of the chloroplasts of all ten of the species examined. In
      contrast, eight red keto-carotenoids are unusually located in several
      plastoglobules present in the stroma of nine species Ceratozamia mexicana Brongn.
      excluded. The characteristic red-brown transitory coloration shown by the newly
      formed leaflets during the first stages of development is due to this latter keto
      mixture. It is constituted of three very rare keto-carotenoids, which were, in
      our case, identified for the first time from the photosynthetic tissues (semi
      beta-carotenone, triphasiaxanthin, and beta-carotenone). It is also constituted
      of four others, which are completely novel (ceratoxanthin, ceratozamiaxanthin,
      kuesteriaxanthin, and ceratoxanthone). Some hypotheses about their presence and
      function are presented.

PMID- 15940870
TI  - Changes in the ascorbate system in the response of pumpkin (Cucurbita pepo L.)
      roots to aluminium stress.
AB  - The involvement of the ascorbate (AsA) system in the response of pumpkin
      (Cucurbita pepo L.) roots to aluminium stress was studied. The treatment of 5-day
      old pumpkin seedlings with 50 microM aluminium sulphate resulted in approximately
      60% inhibition of root growth within 48-60 h of treatment, while aluminium
      accumulated in the roots reaching a maximum within 48h. During the same period,
      the hydrogen peroxide content of the roots was strongly enhanced. The increased
      level of hydrogen peroxide was matched by both increased ascorbate peroxidase
      (APX) (EC 1.11.1.11) activity and ascorbate free radical reductase (AFRR) (EC
      1.1.5.4) activity, while dehydroascorbate reductase (DHAR) (EC 1.8.5.1) and
      glutathione reductase (GR) (EC 1.6.4.2) did not change. The levels of AsA in the
      roots were also increased by the Al treatment. It was concluded that an oxidative
      burst is probably involved in the toxicity of Al in pumpkin roots and that plants
      react to the enhanced production of reactive oxygen species by expressing higher
      levels of scavenging systems such as the AsA-APX system.

PMID- 15940871
TI  - Moderation of morphogenetic and oxidative stress responses in flax in vitro
      cultures by hydroxynonenal and desferrioxamine.
AB  - Hypocotyl segments of 7-day old seedlings of flax (Linum usitatissimum L.)
      cultivars Atalante, Flanders, Jitka, Szegedi 30 and Super were screened for
      organogenesis (shoot and root induction) and embryo-like structure production. A
      non-destructive assay for hydroxyl radicals (*OH), utilising DMSO as a radical
      trap, was used to determine *OH formation during tissue culture and
      morphogenesis. Desferrioxamine, an inhibitor of Fenton reaction, and 4-hydroxy-2
      nonenal, a cytotoxic Lipid peroxidation product, were exogenously applied to flax
      cultures to determine the effect of antioxidative and prooxidative status on
      morphogenetic responses induced through the exogenous application of plant growth
      regulators. Flax genotypes varied in their response to treatments after exposure
      to different plant hormones. Hydroxyl radical (*OH) formation correlated with
      morphogenetic responses and this was affected by plant hormones. Desferrioxamine
      and 4-hydroxy-2-nonenal also moderated morphogenetic responses and influenced
      hydroxyl radical formation during in vitro propagation.

PMID- 15940872
TI  - Freezing tolerance in two Norway spruce (Picea abies [L.] Karst.) progenies is
      physiologically correlated with drought tolerance.
AB  - The goal of the present study was to investigate whether seedlings of Norway
      spruce (Picea abies [L.] Karst.) from a frost tolerant progeny (P2), were more
      drought tolerant than seedlings from a less frost tolerant progeny (P1).
      Progenies differing in freezing tolerance were identified by exposing seedlings
      in autumn in a large-scale trial to temperatures from -11 to -15 degrees C and
      scoring the degree of needle injury. Seedlings from P1 and P2 were grown from
      seeds for about 1 year under controlled conditions in a climatized growth room
      and were exposed to drought stress by withholding water for about 3 weeks.
      Drought caused reductions in biomass in both progenies but to a stronger extent
      in P1 than in P2. Seedlings of P2 were able to fully maintain root biomass. They
      also showed less water loss in different tissues. Decreases in quantum yield
      efficiency of photosystem II of dark-adapted plants occurred several days later
      in P2 than in P1. New proteins of molecular masses of 24.3 and 25.5 kDa appeared
      during drought stress. Since they occurred in both progenies a role of these
      proteins in progeny-related differences in drought performance is unlikely.
      Progeny 2 contained inherently higher superoxide dismutase and lower peroxidase
      activities than progeny 1. In conclusion, freezing and drought-tolerance
      respective -sensitivity were co-occurring traits in the spruce progenies studied
      here. Pre-existing high activities of enzymes protecting against oxidative stress
      in seedlings may have contributed to increase stress tolerance in P2 compared
      with P1.

PMID- 15940873
TI  - Expression of an antisense Datura stramonium S-adenosylmethionine decarboxylase
      cDNA in tobacco: changes in enzyme activity, putrescine-spermidine ratio,
      rhizogenic potential, and response to methyl jasmonate.
AB  - S-adenosylmethionine decarboxylase activity (SAMDC; EC 4.1.1.21) leads to
      spermidine and spermine synthesis through specific synthases which use
      putrescine, spermidine and decarboxylated S-adenosylmethionine as substrates. In
      order to better understand the regulation of polyamine (PA), namely spermidine
      and spermine, biosynthesis, a SAMDC cDNA of Datura stramonium was introduced in
      tobacco (Nicotiana tabacum L. cv. Xanthi) in antisense orientation under the CaMV
      35S promoter, by means of Agrobacterium tumefaciens and leaf disc transformation.
      The effect of the genetic manipulation on PA metabolism, ethylene production and
      plant morphology was analysed in primary transformants (R0), and in the
      transgenic progeny (second generation, R1) of self-fertilised primary
      transformants, relative to empty vector-transformed (pBin19) and wild-type (WT)
      controls. All were maintained in vitro by micropropagation. Primary
      transformants, which were confirmed by Southern and northern analyses,
      efficiently transcribed the antisense SAMDC gene, but SAMDC activity and PA
      titres did not change. By contrast, in most transgenic R1 shoots, SAMDC activity
      was remarkably lower than in controls, and the putrescine-to-spermidine ratio was
      altered, mainly due to increased putrescine, even though putrescine oxidising
      activity (diamine oxidase, EC 1.4.3.6) did not change relative to controls.
      Despite the reduction in SAMDC activity, the production of ethylene, which shares
      with PAs the common precursor SAM, was not influenced by the foreign gene. Some
      plants were transferred to pots and acclimatised in a growth chamber. In these in
      vivo-grown second generation transgenic plants, at the vegetative stage, SAMDC
      activity was scarcely reduced, and PA titres did not change. Finally, the
      rhizogenic potential of in vitro-cultured leaf explants excised from antisense
      plants was significantly diminished as compared with WT ones, and the response to
      methyl jasmonate, a stress-mimicking compound, in terms of PA conjugation, was
      higher and differentially affected in transgenic leaf discs relative to WT ones.
      The effects of SAMDC manipulation are discussed in relation to plant generation,
      culture conditions and response to stress.

PMID- 15940874
TI  - Molecular cloning and characterization of a cotton glucuronosyltranferase gene.
AB  - A glucuronosyltranferase gene has been isolated from cotton (Gossypium hirsutum)
      fiber cells using rapid amplification of the cDNA ends. The full-length cDNA,
      designated GhGlcAT1, is 1400 bp in length (AY346330) and contains an open reading
      frame of 1107 bp encoding a protein of 368 amino acids. Alignment of the GhGlcAT1
      predicted amino acid sequence was shown to have high sequence similarity with
      animal glucuronosyltranferases. A phylogenic tree generated by the PHYLIP program
      package showed that GhGlcAT1 is clustered into the plant glucuronosyltranferase
      proteins and is distinct from those of other species. Homology modeling of the
      GhGlcAT1 structure using Homo sapiens native glucuronosyltranferase (1 kws and 1
      fgg) structure as a template strongly suggests that the main-chain conformation
      and the folding patterns were similar to structural features characteristic of
      animal glucuronosyltranferases. Northern blot analysis showed that the
      transcripts of GhGlcAT1 were abundant in fiber cells, moderate in stem, but not
      detected in ovule, flower, seed, root and leaf. Transcripts were most abundant at
      15dpa fiber. The transcription occurred at both the primary wall elongation stage
      and former stage of secondary cell thickening, suggesting that GhGLcAT1 may be
      involved in non-cellulose polysacchrides biosynthesis of the cotton cell wall.

PMID- 15940875
TI  - Changes in competence for somatic embryogenesis in Norway spruce zygotic embryo
      segments.
AB  - Embryogenic capacity of Norway spruce zygotic embryo sections was drastically
      altered by a preinduction transfer to hormone-free medium for 7 or 14 days. An
      increase in competence for somatic embryogenesis was found with the cotyledons,
      while the hypocotyl sections completely lost their competence. These changes in
      competence were not dependent on physical contact between plant sections, and
      could not be correlated to the developmental stage of each section. The increase
      of competence in cotyledonary material was due not only to an increase of
      genotypes initiating somatic embryos, but also to an increase in embryogenicity
      of cotyledons.

PMID- 15940876
TI  - Fluctuations of different endogenous phenolic compounds and cinnamic acid in the
      first days of the rooting process of cherry rootstock 'GiSelA 5' leafy cuttings.
AB  - The relationship between the phenol composition of rooting zones and rootability
      was studied in the first days after the establishment of cuttings. The trial
      included two different types of cuttings (basal and terminal). Additionally, the
      influence of exogenously applied auxin (IBA) was observed. The best rooting
      results (55.6%) were achieved with terminal IBA treated cuttings, while only 1.9%
      of basal cuttings formed roots. The auxin treatment increased the root formation
      in terminal, but not in basal cuttings. Low rooting rate of basal cuttings was
      probably due to higher lignification rate of the basal tissue which can represent
      a mechanical barrier for root emergence. When measuring phenolic compounds and
      cinnamic acid, terminal cuttings contained higher (rutin, vanillic acid, (-)
      epicatechin, caffeic acid and sinapinic acid) or equal concentrations of detected
      phenols as basal cuttings, while applied auxin did not influence the level of any
      of discussed phenolics, neither of cinnamic acid. It is to assume that cuttings
      for starting of root induction phase should contain certain levels of several
      phenolic compounds, but higher influence on rooting success is to be ascribed to
      the impact of the auxin level. During the time of the experiment concentrations
      of monophenols sinapinic acid and vanillic acid rapidly decreased. This decrease
      was more pronounced in terminal cuttings, which might have a better mechanism of
      lowering those two compounds to which a negative influence on rooting is
      ascribed. Fluctuations and differences between treatments of other phenolics were
      not significant enough to influence the rooting process.

PMID- 15940877
TI  - Changes in content and fatty acid profiles of total lipids and sulfolipids in the
      halophyte Crithmum maritimum under salt stress.
AB  - In the halophyte Crithmum maritimum, the sulfolipid content increased
      considerably in the presence of NaCl. There were no significant changes in the
      total fatty acid composition of sulfolipids during salt treatment, except for
      linoleic and linolenic acids. In comparison to the control plants, sulfolipids in
      NaCl-treated plants showed a decrease in the percentage of unsaturated fatty acid
      (C18:3), and a corresponding increase in the percentage of unsaturated fatty
      acids (C18:2). As a whole, the data reported in this work suggest that sulfolipds
      may be one important aspect of strategies involved in salt tolerance of this
      halophyte.

PMID- 15940878
TI  - Nitrogen transport in the xylem sap of Quercus ilex: the role of ornithine.
AB  - The storage and remobilization of nitrogen in deciduous and evergreen species is
      a major source of N, supporting the seasonal growth of trees. In evergreens, in
      addition to wood and roots, older leaves are important reservoirs of N used in
      the growth of new foliage. Just before bud burst, when transpiration is inactive
      or low, and when uptake of nitrogen by the roots may be restricted due to low
      temperatures, levels of organic N in the xylem are high. Amino acids usually
      comprise the bulk of this organic N. Changes in amino acid concentrations in
      early spring are thought to result mainly from hydrolysis of N reserves, and not
      from current N uptake. The seasonal profiles of amino acids in the xylem sap of
      Quercus ilex, an evergreen Mediterranean tree, were investigated. The first amino
      acid detected in the xylem sap before spring was ornithine, which may result from
      the breakdown of arginine present in storage proteins. Arginine is one of the
      main amino acids present in storage proteins because each arginine molecule has
      four nitrogen atoms. When protein degradation increases the free arginine pool,
      the arginase activity is enhanced and, consequently, the conversion of arginine
      to ornithine. It seems that ornithine has an important role in N transport early
      in the growth season of Q. ilex.

PMID- 15940879
TI  - Demystifying cancer.

PMID- 15940880
TI  - Instructive differences.

PMID- 15940881
TI  - Issue missed the boat.

PMID- 15940882
TI  - Fishing for a cure. Does the tiny zebrafish hold a key to stopping tumor growth?

PMID- 15940883
TI  - Working with cancer.

PMID- 15940884
TI  - Genomic gestalt.

PMID- 15940885
TI  - Breaking news.

PMID- 15940886
TI  - Access to care--should there be winners and losers?

PMID- 15940887
TI  - On the backwaterfront.

PMID- 15940888
TI  - The contenders. Vaccines and viruses take aim at cancer cells.

PMID- 15940889
TI  - Out of the driver's seat. The recurrence of cancer is a far different ride than
      the first diagnosis.

PMID- 15940890
TI  - The reluctant oracle. What is a physician to say when a dying patient asks how
      much time is left?

PMID- 15940891
TI  - Mastering the art of oncology.

PMID- 15940892
TI  - Taking a comprehensive approach to addressing Minnesota's leading cause of death.
      Cancer Plan Minnesota 2005-2010.
AB  - Cancer is now the leading cause of death in Minnesota. Half of all Minnesotans
      will develop a potentially life-threatening cancer in their lifetime, and the
      number of people diagnosed with cancer is projected to increase by 22% between
      2000 and 2010. In 2003, health care providers, health plan representatives,
      patient care advocates, public health professionals, members of volunteer
      organizations, and cancer researchers came together to begin crafting the state's
      first plan to address the full spectrum of cancer control--from prevention and
      early detection to treatment, palliative care, and survivorship. The resulting
      plan is intended to serve as a framework for action by policymakers, planners,
      health care providers, and others, and is grounded in the notion that better
      integration and coordination of cancer control activities and programs will
      result in more effective efforts to address the burden of cancer in Minnesota.

PMID- 15940893
TI  - Recollection of previous colon cancer screening in Minnesota adults.
AB  - Regularly scheduled screening of patients has been shown to be effective for
      decreasing morbidity and mortality from colorectal cancer. We used a
      questionnaire to assess patients' ability to accurately recall the date and type
      of their most recent colorectal cancer screening. The study included 200
      consecutive patients whose records indicated they had undergone previous
      colorectal cancer screening (8 patients were later excluded because they had been
      screened more than 5 years earlier). Overall, 32.3% of patients could not recall
      the date of their last colorectal cancer screening, 34.3% recalled the date
      inaccurately, and 33.3% recalled the date accurately within 1 month. The results
      suggest that recall alone is not sufficient to determine the date and type of
      previous colorectal cancer screening, especially if the screening was performed
      more than a year earlier.

PMID- 15940894
TI  - Holding hope.

PMID- 15940895
TI  - [Validation and regulatory acceptance of alternative methods for toxicity
      evaluation].
AB  - For regulatory acceptance of alternative methods (AMs) to animal toxicity tests,
      their reproducibility and relevance should be determined by intra- and inter
      laboratory validation. Appropriate procedures of the validation and regulatory
      acceptance of AMs were recommended by OECD in 1996. According to those
      principles, several in vitro methods like skin corrosivity tests and
      phototoxicity tests were evaluated and accepted by ECVAM (European Center for the
      Validation of Alternative Methods), ICCVAM (The Interagency Coordinating
      Committee on the Validation of Alternative Methods), and OECD. Because of the
      difficulties in conducting inter-laboratory validation and relatively short
      period remained until EU's ban of animal experiments for safety evaluation of
      cosmetics, ECVAM and ICCVAM have recently started cooperation in validation and
      evaluation of AMs. It is also necessary to establish JaCVAM (Japanese Center for
      the Validation of AM) to contribute the issue and for the evaluation of new
      toxicity tests originated in Japan.

PMID- 15940896
TI  - [NO-release ability and DNA-damage activity of aromatic N-nitroso compounds].
AB  - To develop a new nitric oxide-donor (NO-donor) that is useful for chemical and
      biochemical research, we synthesized several aromatic N-nitroso compounds
      including 1-[N-nitroso-N-(4-tolyl)carbamoyl] piperidine-4-carboxylic acid (1f)
      and phenyl(2-pyridyl)-N-nitrosamines, which spontaneously generate NO at ambient
      temperature. Thermal decomposition of these compounds was run under mild
      conditions. Gaseous NO released from them was quantified by means of the Griess
      reaction using a specially designed apparatus in which NO2- is generated from NO.
      The structure of products arose from the radical cleavage of N-NO bond was
      clarified by chemical and spectral studies. Generation of NO from the N-nitroso
      compounds was also confirmed by ESR spectroscopy. The action of these NO
      releasing compounds against DNA was examined. When the pBR 322 DNA was treated
      with 1f at 37 degrees C for 3 h, the DNA single-strand breaks was 31% for 1 mM of
      1f. The denitrosated compound and sodium nitrite did not show any effective DNA
      cleaving activity. On the other hand, aromatic N-nitrosamines induced weak DNA
      cleaving activity under the same condition.

PMID- 15940897
TI  - Growth characteristics of Cannabis sativa L. cultivated in a phytotron and in the
      field.
AB  - Growth characteristics of Cannabis saliva L. are indispensable factors to verify
      the statements by the criminals of illegal cannabis cultivation. To investigate
      growth characteristics of C. sativa, two varieties, cannabidiolic acid (CBDA)
      rich (CBDA-type) which being cultivated for fiber production and delta9
      tetrahydrocannabinolic acid (THCA)-rich (THCA-type) which is used for drug abuse,
      were cultivated from seeds under the same growth environment in a phytotron. THCA
      type showed high germination rate (100%) whereas only 39% of the CBDA-type seeds
      germinated 6 days after sowing. Plant height, number of true leaves, number of
      nodes, number of axillary buds and flowering of these two varieties were
      periodically observed. THCA-type grew more rapidly (plant height: 125.8 cm for
      THCA-type, 84.7 cm for CBDA-type, 75 days after cultivation) demonstrating
      vigorous axillary bud formation and earlier male-flowering (63 days for THCA
      type, 106 days for CBDA-type, after sowing). Propagation of THCA-type was tested
      using the axillary shoot cuttings of female plants either with or without the
      main stem. All the cuttings with the main stem rooted after 21 days and grew
      healthily in a phytotron. However, all the newly developed leaves were single
      instead of palmate. In the field, THCA-type male-flowered after 155 days of
      cultivation after sowing on March 31. The height of the field-cultivated plants
      reached 260.9 cm 163 days after sowing. Despite the great differences in final
      plant heights, the increases of plant height per day during the vegetative growth
      stage were similar in the field and in the phytotron. Thus estimating the
      starting time of illegal cannabis cultivation might be possible if the plant is
      in the vegetative growth stage.

PMID- 15940898
TI  - [Validation of a method for discrimination of formaldehyde processing in textile
      products].
AB  - It is important to investigate a cause of formaldehyde contamination exceeding a
      regulation limit value in a textile product. If formaldehyde was released from a
      textile product itself by treatment or processing with formaldehyde, an
      administrative guidance is given to a manufacture. On the other hand, when the
      formaldehyde migrated from other textile products or a furniture stand during
      displaying, an improvement instruction is performed to the store. Iwama et al.
      [Ann. Rep. Nagoya City Public Res. Inst., 42, 11-16 (1996)] developed a method
      for distinguishing fabric processing and migration by additional hydrolytic
      extraction using hydrochloric acid solution. This study was to confirm the
      reliability and stability of the method for knowing formaldehyde processing on
      textiles. Five laboratories evaluated three samples: unprocessed textile,
      processed textile and unprocessed but formaldehyde-migrated textile. For a
      processed textile sample, amounts of formaldehyde increased by additional
      extractions with acidic solution, so all laboratories judged that the sample had
      been treated with formaldehyde. In the cases of the other two samples, such
      increases were not observed in the extracts using acidic solution. All
      laboratories reported that these samples were not processed using formaldehyde
      but had absorbed a different level of formaldehyde by migration. In a series of
      experiments, the judgement about the existence of formaldehyde processing or
      migration is comparatively consistent among all laboratories. This validation
      study concluded that the distinguishing method adopting additional extractions
      with acidic solution is useful to find formaldehyde processing of textile, and to
      deal with processing and migration separately as a cause of formaldehyde
      contamination.

PMID- 15940899
TI  - [Studies for analyzing prohibited ingredients such as estriol in cosmetics].
AB  - Estriol (EO) is nominated as the prohibited ingredients in cosmetics in Japanese
      Pharmaceutical Affairs Act. So the analytical method using HPLC for EO was
      investigated. After placing 1.0 ml of EO solution at 50 microg/ml and 0.5 g of
      the lotion into a 10-ml volumetric flask, the methanol was added to make until
      that volume and this solution was used as the testing solution. Milky lotion was
      procedured as follows: After placing 1.0 ml of EO solution at 50 microg/ml and
      0.5 g of the milky lotion into a 10-ml volumetric flask, the methanol was added
      to make until that volume. The suspending mixture was moved to a centrifuging
      tube with a cap. After centrifuging at 3000 rpm for 5 minutes, the supernatant
      was used as the testing solution. The testing solution of 20 microl was
      determined by HPLC using the ODS column (CAPCELL PAK C18 column, 4.6 x 250 mm),
      the mixture of water and acetonitrile (31:9) and the detection wavelength of 285
      nm. The working curve from 1.0 to 6.0 microg/ml showed a linear line between the
      concentrations of EO and the peak area. There was no interference of peak of EO
      from the lotion and milky lotion.

PMID- 15940900
TI  - [Studies for analyzing prohibited ingredients such as tetracaine hydrochloride in
      cosmetics].
AB  - Tetracaine hydrochloride (TH) is nominated as the prohibited ingredients in
      cosmetics in Japanese Pharmaceutical Affairs Act. So the analytical method for TH
      was investigated by HPLC. After adding 5 ml of TH solution at 10 microg/ml and 2
      ml of salicylic acid solution at 75 microg/ml as the internal standard to 0.5 g
      of the lotion, the mixture was made up to 10 ml with a mixture of water and
      methanol (1:1) as the testing solution. Milky lotion was procedured as follows:
      After adding 5 ml of TH solution at 10 microg/ml and 2 ml of internal standard
      solution to 0.5 g of the milky lotion, the mixture was made up to 10 ml with a
      mixture of water and methanol (1:1). Two milliliter of this mixture was placed
      into a centrifuging tube with a cap and 2 ml of hexane was added. After shaking
      vigorously and centrifuging, the lower layer was used as the testing solution. In
      the case of the cream, the other procedures were used: 0.5 g of cream was placed
      into a 10-ml volumetric flask and 1 ml of tetrahydrofuran was added. After
      dissolving, the mixture of methanol and water (1:1) was added to make up 10.0 ml.
      Two milliliter of this mixture was placed into a centrifuging tube with a cap and
      2.0 ml of hexane was added. After shaking vigorously and centrifuging, the lower
      layer was used as the testing solution. The testing solution of 20 microl was
      analyzed by HPLC using the ODS column (CAPCELL PAK C18 column, 4.6 x 250 mm), the
      mixture of acetonitrile and 50 mmol/l phosphate buffer(pH 2.0)(7:3) and the
      detection wavelength of 303 nm. The working curves from 0.5 to 6.0 microg/ml
      showed a linear line between the concentrations of TH and the peak area ratio.
      There was no interference of peak of TH from the lotion, milky lotion and cream.

PMID- 15940901
TI  - [Status of NIHS Computer Network System (NIHS-NET)].
AB  - We described the development of National Institute of Health Sciences Computer
      Network System (NIHS-NET), which was named NIHS Information and Computing
      Infrastructure (NICI) previously. In the system, the main server machines and
      common machines were replaced and the network lines were upgraded from 100 Mbps
      to 1Gbps. The connection nodes were changed from Inter Ministry Network (IMnet)
      to Science Information Network (SINET), and the dedicated lines between NIHS
      (yoga, osaka, tsukuba) and SINET were constructed. The Internet connection speed
      from each campus to SINET was upgraded. We also performed security audit in this
      system.

PMID- 15940902
TI  - [Progress on OECD chemicals programme].
AB  - The twelfth SIDS, the Screening Information Data Set, Initial Assessment Meeting
      (SIAM 12) was held at the Organisation for Economic Co-operation and Development
      (OECD) headquarters in Paris, France and SIAM 13 was held in Bern, Switzerland,
      hosted by the European Commission. Two substances at SIAM 12 (CAS No:91-15-6, 123
      77-3) and 4 substances at SIAM 13 (CAS No:91-76-9, 112-85-6, 868-77-9, 1477-55-0)
      were submitted by the Japanese Government and/or International Council of
      Chemical Associations (ICCA). These substances were agreed at the meetings. In
      this report, the human health effects of 6 substances above-mentioned are
      introduced.

PMID- 15940903
TI  - [Studies for analyzing restricted ingredients such as sodium benzoate].
AB  - Sodium benzoate is a kind of preservatives in cosmetics and is nominated as the
      restricted ingredients in cosmetics in Japanese Pharmaceutical Affairs Act. So
      the analytical method for sodium benzoate was investigated by HPLC. After adding
      5 ml of tetrahydrofuran to 0.05 g of the lotions or creams with 0.1 or 1.0%
      sodium benzoate and dissolving them, that mixture was made up to 50 ml with
      methanol. If necessary, the mixture was filtrated with a membrane filter (0.45
      microm). The testing solution of 20 micro1 was analyzed by HPLC using the ODS
      column (CAPCELL PAK C18 column, 4.6 x 250 mm), the mixture of 50 mmol/l phosphate
      buffer (pH5.5) and acetonitrile (7:3) and the detection wavelength of 227 nm. The
      working curve from 1.0 to 12.0 microg/ml showed a linear line between the
      concentrations of sodium benzoate and the peak area. There was no interference of
      peak of sodium benzoate from the lotion and cream.

PMID- 15940904
TI  - [Estimated production by the official inspection of tar colors (including
      aluminum lakes) in fiscal year 2003].
AB  - There were 197 official inspections of tar colors and their lakes in fiscal year
      2003, the two of their samples were rejected, and the other were qualified. Total
      production amount of tar colors that passed inspection in Japan in fiscal year
      2003 reached 147.9 tons. Tar color production amounts were described by month and
      by manufacturer. The food tar color produced in the largest amount was Food
      Yellow No. 4, accounting for 41.7% during this period.

PMID- 15940906
TI  - [Recent TDI derivation of dioxin based on the reproductive and developmental
      toxicity].
AB  - In 1998, WHO-IPCS re-assessed the TDI of dioxin, which was derived from the body
      burdens of TCDD exposed to the experimental animals. Then, the international
      assessment agencies and governmental assessment agencies have conducted the
      dioxin fs health assessment using the similar method to the WHO-IPCS approach.
      The key endpoints were reproductive and developmental toxicity caused by in utero
      and lactational exposure. Each assessment agencies used the similar data set of
      the toxicity studies, however, there are some differences about the TDI
      derivation method and the selection of adverse endpoints. This report reviewed
      the recent reproductive and developmental toxicity studies of the dioxins and
      summarized the health assessment in the international or governmental agencies,
      and discussed the appropriate TDI derivation.

PMID- 15940905
TI  - [Development of the web system for analysis of toxic drugs and chemicals].
AB  - When poisoning or chemical incident occurs, it is important to examine and
      identify the causal substances rapidly to treat patients properly. In order to
      make it easily accessible for people who analyze samples, we developed the web
      system which provides the analytical methods of drugs and toxic compounds in
      biological samples such as blood and urine. The rapid analytical method using
      Test Kits and the instrumental analysis using GC/MS or HPLC are included. Photos
      of procedures and description on pitfalls during analysis are also included to
      make the system practically.

PMID- 15940907
TI  - [Septic shock: diagnosis and management].
AB  - Sepsis is the most important reason for death among intensive care patients. This
      review will cover the actual definition of septic shock, and the difficulties
      regarding the diagnosis of sepsis. The principles of management of sepsis, the
      recently established principles as early goal directed therapy, low dose steroid
      substitution, insulin therapy, and the activated protein C are discussed.

PMID- 15940908
TI  - [In diabetes and peripheral arterial occlusive disease: long-term treatment with
      clopidogrel].

PMID- 15940909
TI  - [Determination of olfactory function].

PMID- 15940910
TI  - [Communication between physician and patient: art or science?].

PMID- 15940911
TI  - ["Subacute thyreoiditis" without response on corticosteroid therapy].
AB  - A 49-year old employee of a drug store with neck pain, painful thyroid gland, and
      elevated erythrocyte sedimentation rate (38 mm/h) was diagnosed as subacute
      thyreoiditis (de Quervain). However, application of oral corticosteroids
      (prednisone 50 mg/d) during three days did not reduce pain as expected.
      Therefore, the patient was admitted for further evaluation. Clinical examination
      showed a female in a pain-relieving posture (forward neck flexion). Further
      examinations including ultrasound of the thyroid, computertomography of the neck,
      and ENT examination did not reveal etiology of the pain. Finally,
      electrocardiography showed subacute infero-posterior myocardial infarction, and
      coronary angiography revealed severe coronary two vessel disease. Tabacco smoking
      since the age of fourteen (35 pack years) was identified as the only major risk
      factor for premature atherosclerosis. Diagnosis of subacute thyreoiditis is made
      from clinical and laboratory findings. Treatment with nonsteroidal
      antiinflammatory drugs or corticosteroids usually relieves pain within two or
      three days. Otherwise, etiology of the disease must be re-evaluated considering
      any disease localized in neck or thorax region. Antiinflammatory treatment of
      subacute thyreoiditis has to be continued for weeks or months.

PMID- 15940912
TI  - [A small virus among the large].

PMID- 15940913
TI  - [Fever and fatigue].

PMID- 15940914
TI  - [Solution to the medical literature puzzle].

PMID- 15940915
TI  - [Primary adrenal insufficiency in children].
AB  - Three boys, aged 5, 11 and 14 years, were admitted due to vomiting, fatigue and
      dehydration, and a 10-year-old boy was admitted due to circulatory and
      respiratory insufficiency. Two had Addison's disease, one had a late presentation
      of congenital adrenal hypoplasia due to a DAX-1 mutation and in one adrenal
      insufficiency was the first manifestation ofadrenoleukodystrophia. The boys
      recovered after treatment. It is important to recognise the symptoms of adrenal
      insufficiency, because treatment can be life-saving. After the initial diagnosis
      the underlying pathology should be sought.

PMID- 15940916
TI  - [Evidence-based guidelines in the organization of medical care].
AB  - Organizational as well as managerial aspects can influence the outcome of patient
      care, in the establishment of a stroke service unit for instance. Critics wonder
      whether organisational aspects should be excluded from evidence-based guidelines
      as strong evidence is often lacking and managers are not included in the working
      party. It can be argued that it is neither the outcome nor the strength of the
      published evidence that determines whether a guideline is evidence-based but the
      method of guideline development. This includes a systematic search and critical
      appraisal of the literature as well as a rigorous external review in order to
      achieve consensus on statements including those pertaining to organization of
      care, for which evidence is poor or lacking.

PMID- 15940917
TI  - [Pathophysiology and treatment of sickle-cell disease].
AB  - Sickle-cell disease is a hereditary haemoglobinopathy caused by a mutation in the
      beta-globin gene. The disease is characterised by recurrent vaso-occlusive crises
      resulting in severe organ damage and a sharply reduced life expectancy. The
      formation of haemoglobin-S polymers in hypoxic conditions plays a pivotal role in
      sickle-cell disease and produces the characteristic phenotype of sickle-shaped
      erythrocytes that promote vasoocclusion. Endothelial cell activation, enhanced
      erythrocyte and leukocyte adhesion, vasoconstriction and coagulation activation
      play an important role in vaso-occlusive crises. Treatment of pain and hydration
      remain the main interventions in the management ofvaso-occlusive crises.
      Hydroxyurea has been shown to prevent vaso-occlusive crises by increasing the
      amount of foetal haemoglobin. Allogeneic stem-cell transplantation is the only
      curative therapy. However, transplantation-related mortality, graft-versus-host
      disease and the limited availability of HLA-identical donors restrict this
      therapeutic option.

PMID- 15940918
TI  - [Toll-like receptors and the significance for clinical medicine].
AB  - The recently-discovered class of toll-like receptors (TLRs) play an essential
      role in the complex defence system against microorganisms. TLRs are the first to
      detect potential pathogens, initiate immune responses and form the crucial link
      between the innate and acquired immune systems. TLRs also play an important role
      in the pathophysiology of infectious diseases, inflammatory diseases such as
      Crohn's disease and atherosclerosis, and possibly play a role in autoimmune
      diseases. Common polymorphisms in TLR genes are associated with predisposition to
      severe infections. Drugs that target the TLRs offer new opportunities for the
      development of therapeutics against a wide variety of diseases such as sepsis
      syndrome, asthma, inflammatory-bowel diseases and cancer. The first drug that
      works by modulating the TLR response has already been registered.

PMID- 15940919
TI  - [From gene to disease; congenital adrenal hypoplasia and the DAX-1 gene].
AB  - Congenital adrenal hypoplasia is an X-linked disorder resulting in adrenocortical
      deficiency, failure to complete puberty due to hypogonadotrophic hypogonadism,
      and infertility. The disease is caused by mutations in the DAX-1 gene. The DAX-1
      protein is a transcription inhibitor; it represses the transcription of other, as
      yet mostly unknown, genes. Mutation analysis can confirm a clinical diagnosis of
      congenital adrenal hypoplasia. An early diagnosis might prevent critical damage
      due to an adrenal crisis in an undiagnosed patient. Molecular testing can be used
      for carrier detection and genetic counselling.

PMID- 15940920
TI  - [The use of a self-expanding stent as palliation or before elective surgery in
      patients with obstructive colorectal carcinoma].
AB  - OBJECTIVE: To evaluate the use of colorectal stents. DESIGN: Retrospective.
      METHOD: Data were collected on all patients treated at the Deventer Hospital, the
      Netherlands, between 1 April 1996 and 31 December 2003 in whom the placement of a
      self-expanding colorectal stent was attempted. Each patient's physician was
      contacted to inquire about the patient's status, including quality of life with
      the stent in situ. RESULTS: Stent placement was attempted in 57 patients as
      palliation (n = 45) or before elective surgery (n = 12). Of the 57 patients, 29
      were men and 28 were women, and the mean age was 71 years (range: 46-94). All
      patients had colorectal carcinoma, except 1 patient with stenosis following
      ischaemic colitis. Passage of air and faeces occurred immediately after stent
      expansion in 55 of the 57 patients (96%). Perforation during stent placement
      occurred in 2 patients, who subsequently underwent colostomy. 4 additional
      patients required a colostomy due to stent migration within a few hours or days
      after placement (n = 3) or obstruction by tumor growth after 65 days (n = 1).
      Patients in the palliative group had an acceptable quality of life. Those who
      received a stent before elective surgery were able to undergo resection, did not
      require colostomy, and had no postoperative complications. One patient did not
      undergo surgery because of extensive metastases. CONCLUSION: A colorectal stent
      can be used in the palliative treatment of terminal patients with colorectal
      carcinoma before colostomy is considered. Experiences with stents before elective
      surgery were also positive.

PMID- 15940922
TI  - [Cardiac sarcoidosis: improved prognosis through new diagnostic tests and
      treatment].
AB  - Cardiac sarcoidosis was diagnosed in 3 patients: 2 men aged 52 and 51 years,
      respectively, and a woman aged 55 years. Both men had ventricular tachycardia. In
      the first man, a right-ventricle biopsy revealed a non-caseating granuloma. The
      second man had active granulomatous cardiac infiltration, according to a gallium
      scintigram. The first man recovered after receiving immunosuppression, heart
      failure medication, and an implantable defibrillator; the second received the
      same plus radio-frequency catheter ablation, but experienced serious heart
      failure. The woman was being treated for pulmonary sarcoidosis but complained of
      progressive cardiac symptoms. She recovered after receiving heart-failure
      medication, immunosuppression, and a biventricular pacemaker. Sarcoidosis is a
      multi-system granulomatous disorder of unknown aetiology with cardiac involvement
      in 20 to 30% of patients, resulting in severe morbidity and mortality. With the
      help ofgadolinium MRI and positron emission tomography (PET), these conditions
      can be detected at an earlier stage, which allows for improved evaluation of the
      efficacy of available therapies. The use of resynchronisation therapy and
      implantable defibrillators has improved the prognosis of patients with cardiac
      sarcoidosis.

PMID- 15940921
TI  - [A spontaneous haemarthros in a postpartal woman: a case of acquired haemophilia
      A].
AB  - A woman aged 35 years presented with a haemarthros of the left elbow 6 months
      after her first parturition due to acquired haemophilia A. The bleeding episodes
      were mild and treated with recombinant activated factor VII. Because of the mild
      bleeding tendency and the chance of spontaneous remission it was decided to
      withhold immunosuppressive treatment. During the course of one year, the factor
      VIII level and the activated partial thromboplastin time (APTT) normalized and
      the autoantibodies disappeared. Four years after her first parturition, she had
      an uncomplicated pregnancy and the postpartum period was uneventful. Up to
      fourteen months postpartum, there are no signs of recurrence of the acquired
      haemophilia A. Acquired haemophilia A post partum usually presents in the first 3
      months post partum. Frequently presenting symptoms are haemorrhages post partum,
      menorrhagia, soft-tissue haemorrhages and haemorrhages during surgical
      procedures. As a rule, the haemorrhages are slight. The titers of blocking
      antibodies are low in comparison with the titers in congenital haemophilia A.

PMID- 15940923
TI  - [Rubella epidemic in the Netherlands, 2004/'05: awareness of congenital rubella
      syndrome required].
AB  - Rubella is a public health problem due to the teratogenic effects associated with
      primary rubella infection during pregnancy (congenital rubella syndrome).
      Following universal rubella vaccination of infants in the Netherlands, the
      incidence of rubella has declined dramatically. However, since September 2004, an
      outbreak has occurred among unvaccinated individuals, most of whom declined
      vaccination based on religious beliefs. In the period 1 September 2004-22 March
      2005, 166 cases of rubella were reported, including 12 pregnant women. Monitoring
      for signs that the epidemic has spread to other populations in the Netherlands is
      important because this might indicate the need for additional interventions.
      Awareness among health-care workers of the possible occurrence of congenital
      rubella syndrome should be raised. The clinical manifestations of congenital
      rubella syndrome are diverse, can be transient or permanent, and may not present
      until adolescence or adulthood. All cases of laboratory-confirmed rubella
      infection and congenital rubella syndrome should be reported to municipal health
      authorities. There is a possibility that this outbreak will spread abroad. The
      WHO aims to reduce the incidence of congenital rubella syndrome to < 1/100,000
      live births. Health-care workers in the Netherlands should be extra alert to
      detect and notify rubella in a timely manner.

PMID- 15940924
TI  - [A focus on incidents and patient communication skills in the training of
      internists].
AB  - Development of communication skills is an important aspect of the training of
      young physicians. In our hospital, we have developed a programme consisting of
      monthly 1-hour meetings in which the residents in internal medicine discuss
      incidents and communication problems with patients or their relatives. During
      these meetings, residents give feedback to each other under the supervision of
      the consultation-liaison psychiatrist. Important issues that have been discussed
      include refusal of treatment by patients, how to handle aggression, how to
      respond to complaints, relating bad news to patients, euthanasia, and dealing
      with personal problems or work-related stress. The meeting is well attended and
      appreciated by the residents. We believe that this approach of improving
      communication skills based on actual problems encountered in daily practice makes
      a valuable contribution to the training of young doctors.

PMID- 15940925
TI  - [A swelling in the knee cavity, not caused by a Baker's cyst but by a nerve
      sheath tumour].

PMID- 15940926
TI  - [The diagnosis of pulmonary embolism: the best strategies according to the
      results of a large Dutch multicentre study].

PMID- 15940927
TI  - [Summary of the practice guideline 'TIA' (first revision) from the Dutch College
      of General Practitioners].

PMID- 15940928
TI  - [Bad marks for German clinics in osteoporosis--fracture patients almost always
      discharged without therapy].

PMID- 15940929
TI  - [The dilemma with men. Few study data, no guidelines].

PMID- 15940930
TI  - [Headache not taken seriously--could blindness have been prevented?].

PMID- 15940931
TI  - [Insurance patients could have cost-free check-ups: in every 100th patient skin
      cancer was detected (interview by Dr. Judith Neumaier)].

PMID- 15940932
TI  - [Atopic eczema and food allergy: sense and nonsense of diets].

PMID- 15940933
TI  - [Decubitus--signs of the use of mechanical restraints--odd circumstances
      surrounding the death of old patients. Look long and carefully!].

PMID- 15940934
TI  - [Restraining measures in the hospital and nursing home].
AB  - Time and time again, physicians and nursing staff are confronted with a need to
      apply compulsory fixation measures to hospital patients or nursing home
      residents. This may be necessary to protect the physical integrity either of the
      patient himself or of others. When applying coercive measures, careful
      consideration must be given to the respective hazard potential. The care
      providing physician must exercise great care with regard to the selection,
      implementation and documentation of the measures to be employed.

PMID- 15940935
TI  - [Inspection of a corpse by the family physician (general practitioner) in
      practice and nursing home].
AB  - Inspection of a corpse by the physician is a responsible last service he can
      offer his patient. Apart from reliably establishing death and the time of its
      occurrence, the physician must thoroughly inspect the corpse to clarify the cause
      of death. Regrettably, the results of an autopsy are often at odds with the cause
      of death as entered in the death certificate. Poor nursing care and homicides can
      be detected only on the basis of correct information about the cause of death.
      Only then do statistics on causes of death in the population make sense and can
      provide useful data. If an unnatural cause of death is suspected, or if it is not
      possible to ascertain the cause, the police or public prosecutor (coroner) must
      be notified.

PMID- 15940936
TI  - [A therapeutically delicate duo. Hypertension and COPD (interview by Dr. med.
      Jochen Aumiller)].

PMID- 15940937
TI  - [Pruritus--symptom of both skin and systemic diseases].
AB  - Itching is one of the most common complaints affecting the skin. A
      differentiation is made between pruritus in the absence of inflamed skin lesions,
      which is frequently associated with a systemic disease, and pruritus caused by
      inflamed skin, as a symptom of a skin disease. Treatment is directed initially to
      the underlying illness, and both topical and systemic antipruritic medications
      are available as flanking measures.

PMID- 15940938
TI  - [Utilizing progress in modern antihypertensive therapy. Treating hypertension
      effectively from the beginning].

PMID- 15940939
TI  - [A suitable antihypertensive drug of significance. Protection of heart, brain and
      kidney is decisive].

PMID- 15940940
TI  - [Wound management in EBM 2000plus. Reimbursement for cutting, suturing, dressing
      and punctures].

PMID- 15940941
TI  - [Therapy of COPD. Reducing air trapping in the lung--improving physical
      capacity].

PMID- 15940942
TI  - [2005 Robert Koch Award for tiotropium. Quality leap in therapy of COPD].

PMID- 15940943
TI  - [Pain therapy. Extensive possibilities not adequately utilized].

PMID- 15940944
TI  - [10 minute consultation. Extorting the diagnosis... ...when the patient coughs
      for you].

PMID- 15940945
TI  - [Diagnosis at a glance. Nearly asphyxiated by own tongue].

PMID- 15940947
TI  - [RANTES protein protects monkeys from infection with chimeric AIDS viruses].

PMID- 15940948
TI  - [A diarylquinolone active against tuberculosis].

PMID- 15940949
TI  - [A third tumor following SCID gene therapy].

PMID- 15940950
TI  - [The history of ulcer treatment].

PMID- 15940951
TI  - [Proton pump inhibitors].

PMID- 15940952
TI  - [Pharmacology of proton pump inhibitors].

PMID- 15940953
TI  - [ Treatment of peptic ulcers with proton pump inhibitors].

PMID- 15940954
TI  - [Treatment of reflux disease with proton pump inhibitors].

PMID- 15940955
TI  - [Drug preparations of proton pump inhibitors].

PMID- 15940956
TI  - [New drugs for GERD treatment].

PMID- 15940957
TI  - [Proton pump inhibitors in the pharmacy].

PMID- 15940958
TI  - Motor correlates of ADHD: contribution of reading disability and oppositional
      defiant disorder.
AB  - This study investigated whether the likelihood of motor impairment in children
      with attention-deficit/hyperactivity disorder (ADHD) increases with the presence
      of other disorders, and whether the co-occurring diagnoses of reading disability
      (RD) and oppositional defiant disorder (ODD) account for the motor deficits seen
      in ADHD. A total of 291 children (218 boys, 73 girls) participated. Six groups of
      children were compared: ADHD only (n = 29); RD only (n = 63); ADHD and RD (n =
      47); ADHD and ODD (n = 19); ADHD, RD, and ODD (n = 21); and typically developing
      control children (n = 112). Motor skills were assessed with the Bruininks
      Oseretsky Test of Motor Proficiency and the Beery Test of Visual-Motor
      Integration. We found that the motor skills of the ADHD-only group did not differ
      from the typical control group. Furthermore, motor impairment in ADHD increased
      as a function of co-occurring disorders, and the presence of RD rather than ADHD
      predicted motor impairment.

PMID- 15940959
TI  - Working memory in Dutch children with reading- and arithmetic-related LD.
AB  - The aim of the two studies presented in this article was to examine working
      memory performance in Dutch children with various subtypes of learning
      disabilities. The performance of children with reading disabilities (RD) was
      compared to that of children with arithmetic disabilities (AD), children with
      both reading and arithmetic disabilities (RAD), and chronological age-matched
      controls (CA). Measures covered the phonological loop, the visuospatial
      sketchpad, and the central executive. In both studies, the children with RD
      showed no working memory deficits whatsoever. Children with AD showed a single
      impairment on the task tapping working memory for dynamic visual information.
      Children with RAD performed lower only on the digit span backward task. The
      failure to replicate the expected working memory deficits in children with
      reading-related disabilities is discussed.

PMID- 15940960
TI  - Genetic influences on specific versus nonspecific language impairment in 4-year
      old twins.
AB  - The present study addresses the distinction between specific (SLI) and
      nonspecific (NLI) language impairment at an etiological level by estimating the
      relative genetic and environmental contributions to language impairment in
      children with SLI and NLI. Drawing on a large longitudinal twin study, we tested
      a sample of 356 four-and-a-half-year-old children with low language ability and
      their twin partners at home on a range of language and nonverbal measures. For
      children whose language and nonverbal abilities were both low (NLI), genetic
      influence on language impairment was moderate and shared environmental influence
      was substantial. A similar pattern emerged for children whose language
      difficulties occurred in apparent isolation (SLI), although there was a trend for
      the genetic effects to be smaller for SLI than for NLI: Group heritability was
      .18 for SLI and .52 for NLI. Probandwise cross-concordances were suggestive of
      some genetic overlap between these two groups, but not with a subgroup of
      children with more severe cognitive delay.

PMID- 15940961
TI  - Self-determination perceptions and behaviors of diverse students with LD during
      the transition planning process.
AB  - Transition models include components of student self-determination during
      transition planning meetings. Researchers acknowledge that cultural identity may
      influence both transition decisions and self-determination strategies. Yet the
      appropriateness of these approaches for culturally and linguistically diverse
      students with learning disabilities (LD) remains unknown. This study examined
      self-determination perceptions and behaviors of European American, African
      American, and Hispanic American male adolescents with LD. Data were collected
      during focus group and individual interviews, observations, and document reviews.
      Qualitative data analysis provided information about students' behaviors and
      perceptions during postsecondary transition planning. The findings indicated that
      differences within this group of diverse participants were subtle. Students
      identified themselves and family members--rather than teachers--as key players in
      transition planning. Students perceived that self-determination efforts were
      thwarted in school contexts, whereas self-determination opportunities in home
      contexts were more accessible and productive.

PMID- 15940962
TI  - Sources of error in constructing and interpreting graphs: a study of fourth- and
      fifth-grade students with LD.
AB  - The purpose of this study was to examine students' understanding of and ability
      to interpret line graphs, using four tasks: two where students constructed a
      graph and two where students interpreted a given graph. The tasks were unique in
      that they did not simply involve the explanation of given data but included a
      language component that looked at students' cognitive processes and understanding
      while they were engaged in the tasks. The study is important because students are
      often able to define and even draw graphs yet perform poorly on graph
      interpretation items presented in high-stakes examinations. The sample for the
      study consisted of 91 fourth and fifth graders with and without learning
      disabilities (LD) from six schools in a major metropolitan area. Scoring rubrics
      were designed for each item. An analysis of variance by grade and group indicated
      no significant differences between fourth and fifth graders overall but revealed
      that typically achieving students performed at significantly higher levels than
      students with LD at both grade levels. Additional descriptive analyses looked at
      the patterns of errors evidenced and the nature of the students' constructions.
      These are discussed, and instructional implications are derived.

PMID- 15940964
TI  - Widening the nurse recruitment net.

PMID- 15940963
TI  - Why children with ADHD do not have low IQs.
AB  - The major cognitive deficit of children with attention-deficit/hyperactivity
      disorder (ADHD) is impaired executive function (EF), a cognitive component that
      some theorists believe to be the primary substrate for the general intelligence
      (g) factor. We review the constructs of g and EF and the relevant research
      findings on ADHD. We then analyze the results of a battery of diverse tests,
      including measures of EF, administered to 123 boys with ADHD. The correlations
      among the EF measures, two well-accepted measures of IQ, and the g factor
      extracted from the entire battery are trivial at best. These results are
      discussed in the context of collateral evidence supporting the independence of g
      and EF and its clinical and theoretical implications.

PMID- 15940966
TI  - Treating the untreatable.

PMID- 15940965
TI  - Volunteering can work for all.

PMID- 15940968
TI  - Fragile X.

PMID- 15940967
TI  - Draft guidance on treatment and prevention of MRSA.
AB  - New draft guidelines have been prepared on the treatment and prophylaxis of MRSA.
      This article outlines their content and discusses the development and management
      of this bacteria.

PMID- 15940969
TI  - Hepatitis B vaccine.

PMID- 15940970
TI  - Monitoring pulse.

PMID- 15940971
TI  - The use and benefits of compression stocking aids.
AB  - An exploratory study was undertaken to trial various stocking aids designed for
      use with compression and antiembolic hosiery. Their features were identified and
      assessed by professionals for ease of use. Factors affecting the choice of
      stocking aids were the style and grade of stockings and the physical ability of
      users.

PMID- 15940972
TI  - Managing constipation in advanced cancer care.
AB  - Constipation is a common and debilitating symptom in patients with advanced
      cancer. If ignored, constipation will get worse. If left untreated, it can
      greatly reduce a patient's quality of life. An improved understanding of bowel
      function and knowledge of the recognised risk factors will lead to a greater
      appreciation of the signs and symptoms of constipation.

PMID- 15940973
TI  - Developing roles in critical care outreach.

PMID- 15940974
TI  - Helping people assert their rights.

PMID- 15940975
TI  - Nursing is more than meeting targets.

PMID- 15940976
TI  - Time to re-think policies for routine HIV screening.

PMID- 15940977
TI  - Multi-site diabetes initiative targets inpatient and outpatient care.
AB  - Recognizing that routine diabetes care has simply not kept pace with the science,
      Irving, TX-based VHA is on a mission to help its member facilities boost their
      performance on a number of inpatient and outpatient parameters. While goals for
      the effort are uniform, each member site has been charged with developing its own
      roadmap--essentially producing a flurry of quality improvement activities that
      take aim at common problems.

PMID- 15940978
TI  - Summit yields urgent call to eliminate disparities in CVD care.
AB  - Fresh data and new insight have been added to the debate over how to make sure
      that racial and ethnic minorities receive the same level of cardiovascular care
      as white patients. It's a problem that has been documented year after year, and
      yet new surveys suggest that many providers seem unaware of the problem. In an
      effort to tackle the issue head on, experts have presented a multifaceted plan of
      action designed to get attention and get results.

PMID- 15940979
TI  - Asthma DM program demonstrates substantial savings in CO pilot study.
AB  - Investigators at Denver, CO-based National Jewish Medical and Research Center
      think it might account, at least in part, for the outstanding results its program
      produced in a pilot study involving CO Medicaid recipients. In fact, the results
      showed that the asthma program can more than pay for itself, and the state is now
      offering it to all its eligible Medicaid members.

PMID- 15940980
TI  - The Old Medical-Surgical Journal Club, 1956-2004: A legacy of Delaware's Academy
      of Medicine.

PMID- 15940981
TI  - Doctrine of continuing medical treatment.

PMID- 15940982
TI  - Neural network learning algorithms for tracking minor subspace in high
      dimensional data stream.
AB  - A novel random-gradient-based algorithm is developed for online tracking the
      minor component (MC) associated with the smallest eigenvalue of the
      autocorrelation matrix of the input vector sequence. The five available learning
      algorithms for tracking one MC are extended to those for tracking multiple MCs or
      the minor subspace (MS). In order to overcome the dynamical divergence properties
      of some available random-gradient-based algorithms, we propose a modification of
      the Oja-type algorithms, called OJAm, which can work satisfactorily. The
      averaging differential equation and the energy function associated with the OJAm
      are given. It is shown that the averaging differential equation will globally
      asymptotically converge to an invariance set. The corresponding energy or
      Lyapunov functions exhibit a unique global minimum attained if and only if its
      state matrices span the MS of the autocorrelation matrix of a vector data stream.
      The other stationary points are saddle (unstable) points. The globally
      convergence of OJAm is also studied. The OJAm provides an efficient online
      learning for tracking the MS. It can track an orthonormal basis of the MS while
      the other five available algorithms cannot track any orthonormal basis of the MS.
      The performances of the relative algorithms are shown via computer simulations.

PMID- 15940983
TI  - From projection pursuit and CART to adaptive discriminant analysis?
AB  - While many efforts have been put into the development of nonlinear approximation
      theory and its applications to signal and image compression, encoding and
      denoising, there seems to be very few theoretical developments of adaptive
      discriminant representations in the area of feature extraction, selection and
      signal classification. In this paper, we try to advocate the idea that such
      developments and efforts are worthwhile, based on the theorerical study of a data
      driven discriminant analysis method on a simple--yet instructive--example. We
      consider the problem of classifying a signal drawn from a mixture of two classes,
      using its projections onto low-dimensional subspaces. Unlike the linear
      discriminant analysis (LDA) strategy, which selects subspaces that do not depend
      on the observed signal, we consider an adaptive sequential selection of
      projections, in the spirit of nonlinear approximation and classification and
      regression trees (CART): at each step, the subspace is enlarged in a direction
      that maximizes the mutual information with the unknown class. We derive explicit
      characterizations of this adaptive discriminant analysis (ADA) strategy in two
      situations. When the two classes are Gaussian with the same covariance matrix but
      different means, the adaptive subspaces are actually nonadaptive and can be
      computed with an algorithm similar to orthonormal matching pursuit. When the
      classes are centered Gaussians with different covariances, the adaptive subspaces
      are spanned by eigen-vectors of an operator given by the covariance matrices
      (just as could be predicted by regular LDA), however we prove that the order of
      observation of the components along these eigen-vectors actually depends on the
      observed signal. Numerical experiments on synthetic data illustrate how data
      dependent features can be used to outperform LDA on a classification task, and we
      discuss how our results could be applied in practice.

PMID- 15940984
TI  - Deterministic convergence of an online gradient method for BP neural networks.
AB  - Online gradient methods are widely used for training feedforward neural networks.
      We prove in this paper a convergence theorem for an online gradient method with
      variable step size for backward propagation (BP) neural networks with a hidden
      layer. Unlike most of the convergence results that are of probabilistic and
      nonmonotone nature, the convergence result that we establish here has a
      deterministic and monotone nature.

PMID- 15940985
TI  - Efficient training algorithms for a class of shunting inhibitory convolutional
      neural networks.
AB  - This article presents some efficient training algorithms, based on first-order,
      second-order, and conjugate gradient optimization methods, for a class of
      convolutional neural networks (CoNNs), known as shunting inhibitory convolution
      neural networks. Furthermore, a new hybrid method is proposed, which is derived
      from the principles of Quickprop, Rprop, SuperSAB, and least squares (LS).
      Experimental results show that the new hybrid method can perform as well as the
      Levenberg-Marquardt (LM) algorithm, but at a much lower computational cost and
      less memory storage. For comparison sake, the visual pattern recognition task of
      face/nonface discrimination is chosen as a classification problem to evaluate the
      performance of the training algorithms. Sixteen training algorithms are
      implemented for the three different variants of the proposed CoNN architecture:
      binary-, Toeplitz- and fully connected architectures. All implemented algorithms
      can train the three network architectures successfully, but their convergence
      speed vary markedly. In particular, the combination of LS with the new hybrid
      method and LS with the LM method achieve the best convergence rates in terms of
      number of training epochs. In addition, the classification accuracies of all
      three architectures are assessed using ten-fold cross validation. The results
      show that the binary- and Toeplitz-connected architectures outperform slightly
      the fully connected architecture: the lowest error rates across all training
      algorithms are 1.95% for Toeplitz-connected, 2.10% for the binary-connected, and
      2.20% for the fully connected network. In general, the modified Broyden-Fletcher
      Goldfarb-Shanno (BFGS) methods, the three variants of LM algorithm, and the new
      hybrid/LS method perform consistently well, achieving error rates of less than 3%
      averaged across all three architectures.

PMID- 15940986
TI  - Enhanced FMAM based on empirical kernel map.
AB  - The existing morphological auto-associative memory models based on the
      morphological operations, typically including morphological auto-associative
      memories (auto-MAM) proposed by Ritter et al. and our fuzzy morphological auto
      associative memories (auto-FMAM), have many attractive advantages such as
      unlimited storage capacity, one-shot recall speed and good noise-tolerance to
      single erosive or dilative noise. However, they suffer from the extreme
      vulnerability to noise of mixing erosion and dilation, resulting in great
      degradation on recall performance. To overcome this shortcoming, we focus on FMAM
      and propose an enhanced FMAM (EFMAM) based on the empirical kernel map. Although
      it is simple, EFMAM can significantly improve the auto-FMAM with respect to the
      recognition accuracy under hybrid-noise and computational effort. Experiments
      conducted on the thumbnail-sized faces (28 x 23 and 14 x 11) scaled from the ORL
      database show the average accuracies of 92%, 90%, and 88% with 40 classes under
      10%, 20%, and 30% randomly generated hybrid-noises, respectively, which are far
      higher than the auto-FMAM (67%, 46%, 31%) under the same noise levels.

PMID- 15940987
TI  - Chaotic neurodynamics for autonomous agents.
AB  - Mesoscopic level neurodynamics study the collective dynamical behavior of neural
      populations. Such models are becoming increasingly important in understanding
      large-scale brain processes. Brains exhibit aperiodic oscillations with a much
      more rich dynamical behavior than fixed-point and limit-cycle approximation
      allow. Here we present a discretized model inspired by Freeman's K-set mesoscopic
      level population model. We show that this version is capable of replicating the
      important principles of aperiodic/chaotic neurodynamics while being fast enough
      for use in real-time autonomous agent applications. This simplification of the K
      model provides many advantages not only in terms of efficiency but in simplicity
      and its ability to be analyzed in terms of its dynamical properties. We study the
      discrete version using a multilayer, highly recurrent model of the neural
      architecture of perceptual brain areas. We use this architecture to develop
      example action selection mechanisms in an autonomous agent.

PMID- 15940988
TI  - Global asymptotic stability analysis of bidirectional associative memory neural
      networks with time delays.
AB  - This paper presents a sufficient condition for the existence, uniqueness and
      global asymptotic stability of the equilibrium point for bidirectional
      associative memory (BAM) neural networks with distributed time delays. The
      results impose constraint conditions on the network parameters of neural system
      independently of the delay parameter, and they are applicable to all continuous
      nonmonotonic neuron activation functions. It is shown that in some special cases
      of the results, the stability criteria can be easily checked. Some examples are
      also given to compare the results with the previous results derived in the
      literature.

PMID- 15940989
TI  - Mutation-based genetic neural network.
AB  - Evolving gradient-learning artificial neural networks (ANNs) using an
      evolutionary algorithm (EA) is a popular approach to address the local optima and
      design problems of ANN. The typical approach is to combine the strength of
      backpropagation (BP) in weight learning and EA's capability of searching the
      architecture space. However, the BP's "gradient descent" approach requires a
      highly computer-intensive operation that relatively restricts the search coverage
      of EA by compelling it to use a small population size. To address this problem,
      we utilized mutation-based genetic neural network (MGNN) to replace BP by using
      the mutation strategy of local adaptation of evolutionary programming (EP) to
      effect weight learning. The MGNN's mutation enables the network to dynamically
      evolve its structure and adapt its weights at the same time. Moreover, MGNN's EP
      based encoding scheme allows for a flexible and less restricted formulation of
      the fitness function and makes fitness computation fast and efficient. This makes
      it feasible to use larger population sizes and allows MGNN to have a relatively
      wide search coverage of the architecture space. MGNN implements a stopping
      criterion where overfitness occurrences are monitored through "sliding-windows"
      to avoid premature learning and overlearning. Statistical analysis of its
      performance to some well-known classification problems demonstrate its good
      generalization capability. It also reveals that locally adapting or scheduling
      the strategy parameters embedded in each individual network may provide a proper
      balance between the local and global searching capabilities of MGNN.

PMID- 15940990
TI  - Auditory learning: a developmental method.
AB  - Motivated by the human autonomous development process from infancy to adulthood,
      we have built a robot that develops its cognitive and behavioral skills through
      real-time interactions with the environment. We call such a robot a developmental
      robot. In this paper, we present the theory and the architecture to implement a
      developmental robot and discuss the related techniques that address an array of
      challenging technical issues. As an application, experimental results on a real
      robot, self-organizing, autonomous, incremental learner (SAIL), are presented
      with emphasis on its audition perception and audition-related action generation.
      In particular, the SAIL robot conducts the auditory learning from unsegmented and
      unlabeled speech streams without any prior knowledge about the auditory signals,
      such as the designated language or the phoneme models. Neither available before
      learning starts are the actions that the robot is expected to perform. SAIL
      learns the auditory commands and the desired actions from physical contacts with
      the environment including the trainers.

PMID- 15940991
TI  - A performance analysis of two approximate adaptive designs.
AB  - The performance of function approximator based adaptive control designs may scale
      badly with approximator dimension. For a simple system class, both projection
      based designs and multiresolution approximation based designs have been shown to
      have good scaling properties with respect to to linear quadratic (LQ) costs. Here
      we show that by considering a cost functional with penalties on the control rate,
      the multiresolution approximator based design can outperform the projection based
      design. Generalizations are briefly discussed.

PMID- 15940992
TI  - Adaptive neural control for a class of nonlinearly parametric time-delay systems.
AB  - In this paper, an adaptive neural controller for a class of time-delay nonlinear
      systems with unknown nonlinearities is proposed. Based on a wavelet neural
      network (WNN) online approximation model, a state feedback adaptive controller is
      obtained by constructing a novel integral-type Lyapunov-Krasovskii functional,
      which also efficiently overcomes the controller singularity problem. It is shown
      that the proposed method guarantees the semiglobal boundedness of all signals in
      the adaptive closed-loop systems. An example is provided to illustrate the
      application of the approach.

PMID- 15940993
TI  - Missile guidance law design using adaptive cerebellar model articulation
      controller.
AB  - An adaptive cerebellar model articulation controller (CMAC) is proposed for
      command to line-of-sight (CLOS) missile guidance law design. In this design, the
      three-dimensional (3-D) CLOS guidance problem is formulated as a tracking problem
      of a time-varying nonlinear system. The adaptive CMAC control system is comprised
      of a CMAC and a compensation controller. The CMAC control is used to imitate a
      feedback linearization control law and the compensation controller is utilized to
      compensate the difference between the feedback linearization control law and the
      CMAC control. The online adaptive law is derived based on the Lyapunov stability
      theorem to learn the weights of receptive-field basis functions in CMAC control.
      In addition, in order to relax the requirement of approximation error bound, an
      estimation law is derived to estimate the error bound. Then the adaptive CMAC
      control system is designed to achieve satisfactory tracking performance.
      Simulation results for different engagement scenarios illustrate the validity of
      the proposed adaptive CMAC-based guidance law.

PMID- 15940994
TI  - Survey of clustering algorithms.
AB  - Data analysis plays an indispensable role for understanding various phenomena.
      Cluster analysis, primitive exploration with little or no prior knowledge,
      consists of research developed across a wide variety of communities. The
      diversity, on one hand, equips us with many tools. On the other hand, the
      profusion of options causes confusion. We survey clustering algorithms for data
      sets appearing in statistics, computer science, and machine learning, and
      illustrate their applications in some benchmark data sets, the traveling salesman
      problem, and bioinformatics, a new field attracting intensive efforts. Several
      tightly related topics, proximity measure, and cluster validation, are also
      discussed.

PMID- 15940995
TI  - High-speed face recognition based on discrete cosine transform and RBF neural
      networks.
AB  - In this paper, an efficient method for high-speed face recognition based on the
      discrete cosine transform (DCT), the Fisher's linear discriminant (FLD) and
      radial basis function (RBF) neural networks is presented. First, the
      dimensionality of the original face image is reduced by using the DCT and the
      large area illumination variations are alleviated by discarding the first few low
      frequency DCT coefficients. Next, the truncated DCT coefficient vectors are
      clustered using the proposed clustering algorithm. This process makes the
      subsequent FLD more efficient. After implementing the FLD, the most
      discriminating and invariant facial features are maintained and the training
      samples are clustered well. As a consequence, further parameter estimation for
      the RBF neural networks is fulfilled easily which facilitates fast training in
      the RBF neural networks. Simulation results show that the proposed system
      achieves excellent performance with high training and recognition speed, high
      recognition rate as well as very good illumination robustness.

PMID- 15940996
TI  - Image shadow removal using pulse coupled neural network.
AB  - This paper introduces an approach for image shadow removal by using pulse coupled
      neural network (PCNN), based on the phenomena of synchronous pulse bursts in the
      animal visual cortexes. Two shadow-removing criteria are proposed. These two
      criteria decide how to choose the optimal parameter (the linking strength beta).
      The computer simulation results of shadow removal based on PCNN show that if
      these two criteria are satisfied, shadows are removed completely and the shadow
      removed images are almost as the same as the original nonshadowed images. The
      shadow removal results are independent of changes of intensities of shadows in
      some range and variations of the places of shadows. When the first criterion is
      satisfied, even if the second criterion is not satisfied, as to natural grey
      images that have abundant grey levels, shadows also can be removed and PCNN
      shadow-removed images retain the shapes of the objects in original images. These
      two criteria also can be used for color images by dividing a color image into
      three channels (R, G, B). For shadows varying drastically, such as the noisy
      points in images, these two criteria are still right, but difficult to satisfy.
      Therefore, this approach can efficiently remove shadows that do not include the
      random noise.

PMID- 15940997
TI  - Decision feedback recurrent neural equalization with fast convergence rate.
AB  - Real-time recurrent learning (RTRL), commonly employed for training a fully
      connected recurrent neural network (RNN), has a drawback of slow convergence
      rate. In the light of this deficiency, a decision feedback recurrent neural
      equalizer (DFRNE) using the RTRL requires long training sequences to achieve good
      performance. In this paper, extended Kalman filter (EKF) algorithms based on the
      RTRL for the DFRNE are presented in state-space formulation of the system, in
      particular for complex-valued signal processing. The main features of global EKF
      and decoupled EKF algorithms are fast convergence and good tracking performance.
      Through nonlinear channel equalization, performance of the DFRNE with the EKF
      algorithms is evaluated and compared with that of the DFRNE with the RTRL.

PMID- 15940998
TI  - Blind equalization using a predictive radial basis function neural network.
AB  - In this paper, we propose a novel blind equalization approach based on radial
      basis function (RBF) neural networks. By exploiting the short-term predictability
      of the system input, a RBF neural net is used to predict the inverse filter
      output. It is shown here that when the prediction error of the RBF neural net is
      minimized, the coefficients of the inverse system are identical to those of the
      unknown system. To enhance the identification performance in noisy environments,
      the improved least square (ILS) method based on the concept of orthogonal
      distance to red the estimation bias caused by additive measurement noise is
      proposed here to perform the training. The convergence rate of the ILS learning
      is analyzed, and the asymptotic mean square error (MSE) of the proposed
      predictive RBF identification method is derived theoretically. Monte Carlo
      simulations show that the proposed method is effective for blind system
      identification. The new blind technique is then applied to two practical
      applications: equalization of real-life radar sea clutter collected at the east
      coast of Canada and deconvolution of real speech signals. In both cases, the
      proposed blind equalization technique is found to perform satisfactory even when
      the channel effects and measurement noise are strong.

PMID- 15940999
TI  - Zeroing polynomials using modified constrained neural network approach.
AB  - This paper proposes new modified constrained learning neural root finders (NRFs)
      of polynomial constructed by backpropagation network (BPN). The technique is
      based on the relationships between the roots and the coefficients of polynomial
      as well as between the root moments and the coefficients of the polynomial. We
      investigated different resulting constrained learning algorithms (CLAs) based on
      the variants of the error cost functions (ECFs) in the constrained BPN and
      derived a new modified CLA (MCLA), and found that the computational complexities
      of the CLA and the MCLA based on the root-moment method (RMM) are the order of
      polynomial, and that the MCLA is simpler than the CLA. Further, we also discussed
      the effects of the different parameters with the CLA and the MCLA on the NRFs. In
      particular, considering the coefficients of the polynomials involved in practice
      to possibly be perturbed by noisy sources, thus, we also evaluated and discussed
      the effects of noises on the two NRFs. Finally, to demonstrate the advantage of
      our neural approaches over the nonneural ones, a series of simulating experiments
      are conducted.

PMID- 15941000
TI  - An analysis of neural models for walking control.
AB  - A large space of different neural models exists from simple mathematical
      abstractions to detailed biophysical representations with strongly differing
      levels of complexity and biological relevance. Previous comparisons between
      models have looked at biological realism or mathematical tractability rather than
      expressive power. This paper, however, investigates whether more sophisticated
      models are better suited to a complex sensorimotor control task than simpler
      ones, or whether the more general nature of groups of the simpler neurons allows
      them to collectively solve complex tasks better despite their individual
      simplicity. Many models have been proposed or used for sensorimotor control tasks
      such as the control of locomotion. Four such neural models with varying levels of
      complexity were chosen. Controllers made of networks of each neural type were
      evolved to generate locomotion in a simulated dynamically stable four-legged
      robot using a genetic algorithm. The problem domain was chosen as one for which
      no simple solution could be hand crafted and which, with its tight sensorimotor
      coupling, had strongly time-dependent properties as is common in many biological
      control tasks. Analysis of the results shows that the most complex and
      biologically based model is significantly better at walking control, even
      producing recognizable gaits.

PMID- 15941001
TI  - Landmine detection and classification with complex-valued hybrid neural network
      using scattering parameters dataset.
AB  - Neural networks have been applied to landmine detection from data generated by
      different kinds of sensors. Real-valued neural networks have been used for
      detecting landmines from scattering parameters measured by ground penetrating
      radar (GPR) after disregarding phase information. This paper presents results
      using complex-valued neural networks, capable of phase-sensitive detection
      followed by classification. A two-layer hybrid neural network structure
      incorporating both supervised and unsupervised learning is proposed to detect and
      then classify the types of landmines. Tests are also reported on a benchmark
      data.

PMID- 15941002
TI  - A MOSFET-based model of a Class 2 nerve membrane.
AB  - We have constructed a nerve membrane using MOSFET circuitry, which can be a basic
      element of an FET-based neural system. Its mechanism of action potentials
      generation is designed to reproduce that of the Hodgkin-Huxley equations. The
      responses to singlet, doublet, repetitive pulse, and sustained stimuli are
      analyzed to show that it exhibits similar properties to the Hodgkin-Huxley
      equations; namely, 1) excitable dynamics with generation of action potentials, 2)
      the existence of a chaotic response to periodic stimuli, and 3) Class 2
      excitability. It is known that Class 2 excitability is generated by an inverted
      Hopf bifurcation. We have applied Hopf bifurcation theory to our nerve membrane's
      system equations and have shown a routine for ascertaining whether a certain
      parameter set generates an inverted Hopf bifurcation.

PMID- 15941003
TI  - Rigorous proof of termination of SMO algorithm for support vector machines.
AB  - Sequential minimal optimization (SMO) algorithm is one of the simplest
      decomposition methods for learning of support vector machines (SVMs). Keerthi and
      Gilbert have recently studied the convergence property of SMO algorithm and given
      a proof that SMO algorithm always stops within a finite number of iterations. In
      this letter, we point out the incompleteness of their proof and give a more
      rigorous proof.

PMID- 15941004
TI  - Comments on "The multisynapse neural network and its application to fuzzy
      clustering".
AB  - In the above-mentioned paper, Wei and Fahn proposed a neural architecture, the
      multisynapse neural network, to solve constrained optimization problems including
      high-order, logarithmic, and sinusoidal forms, etc. As one of its main
      applications, a fuzzy bidirectional associative clustering network (FBACN) was
      proposed for fuzzy-partition clustering according to the objective-functional
      method. The connection between the objective-functional-based fuzzy c-partition
      algorithms and FBACN is the Lagrange multiplier approach. Unfortunately, the
      Lagrange multiplier approach was incorrectly applied so that FBACN does not
      equivalently minimize its corresponding constrained objective-function.
      Additionally, Wei and Fahn adopted traditional definition of fuzzy c-partition,
      which is not satisfied by FBACN. Therefore, FBACN can not solve constrained
      optimization problems, either.

PMID- 15941005
TI  - Comments on "A generalized LMI-based approach to the global asymptotic stability
      of delayed cellular neural networks".
AB  - In this letter, we point out that the linear matrix inequality (LMI)-based
      criterion obtained in the above paper for the global exponential stability of the
      delayed neural networks can be simplified to a simpler but equivalent form and,
      thus, show that it is not necessary to have such complex form of condition in the
      above paper. As a result, we also answer the question raised by the author of the
      above paper.

PMID- 15941006
TI  - Urinary nickel: measurement of exposure by inductively coupled plasma argon
      emission spectrometry.
AB  - Nickel is a rare earth metal and is widely used in modern industry. Its
      overexposure in human beings can provoke significant effects including lung,
      cardiovascular and kidney diseases. As an index of occupational exposure, urine
      is widely used for the monitoring of nickel concentration because it is a
      minimally invasive method. Recent studies have used atomic absorption
      spectrometry to measure nickel concentration. In this study, we introduced novel
      inductively coupled plasma argon emission spectrometry (ICPAES) which enables us
      to measure multiple elements simultaneously with smaller volume and with lower
      detection limits compared to conventional atomic absorption emission
      spectrometry, and we established the new measuring method by determining the
      appropriate wavelengths for nickel concentration. Furthermore, using the
      established new measuring method, we investigated the correlation between a
      single oral administration of nickel and urine elimination in rats. As a result,
      different concentrations of nickel standard solutions were measured by ICPAES,
      and among five specific wavelengths of nickel, 221.647 and 231.604 nm were chosen
      because they had the highest inclines of both signal to background ratio and
      emission intensity in simple linear regression analysis. Next, by using healthy
      human urine samples that had not been exposed to nickel, 231.604 nm was
      determined to be the most appropriate wavelength because it did not present
      abnormal intensity due to obstacle wavelength. Male Wistar rats received an oral
      administration of nickel ranging from 0.025 to 250 mg/kg, which is equivalent to
      0.0015 - 15% of LD50, and during the following 24 h, urine samples were collected
      and the nickel concentration was measured by ICPAES. With a single oral
      administration of nickel, there was an increase in urine nickel concentration in
      a dose-dependent manner and the appropriate equation was developed. Acute renal
      failure was not observed in this dosage of oral nickel administration by
      analysing NAG, beta2-microglobulin, urine albumin and urine protein. It was
      concluded that the obtained nickel reference values using ICPAES would be useful
      for the early diagnosis of nickel intoxication and in the assessment of the
      exposure to nickel.

PMID- 15941007
TI  - Percutaneous absorption and skin irritation upon low-level prolonged dermal
      exposure to nonane, dodecane and tetradecane in hairless rats.
AB  - Even though the dermal toxicity of hydrocarbon fuels has been well established in
      the literature, there is little information available on the dermal penetration
      kinetics and irritation potential of the individual hydrocarbons. The penetration
      and skin retention of nonane, dodecane and tetradecane was assessed in vitro
      using hairless rats' skin. The effects of unocclusive dermal exposures of these
      chemicals (15 microL every 2 h for 8 h a day for four days) on the transepidermal
      water loss (TEWL) and erythema were measured in CD hairless rats. The expression
      of interleukin 1alpha (IL- 1alpha) and TNF-alpha in the skin and blood were
      measured at the end of dermal exposures. The flux of dodecane was 3- and 77-fold
      higher than nonane and tetradecane. The retention of chemicals in stratum corneum
      (SC) was in the order of tetradecane > dodecane > nonane, and directly correlated
      to the log Kp (r2 = 0.9900) and molecular weight of the chemicals (r2 = 0.8782).
      The TEWL and erythema data indicate that irritation was in the following order:
      tetradecane > dodecane > nonane. Likewise, the expression of IL-lalpha in the
      blood and TNF-alpha in the skin after dermal exposures was higher for tetradecane
      followed by dodecane and nonane compared to control. In conclusion, the aliphatic
      hydrocarbon chemicals of the present study induced cumulative irritation upon low
      level repeat exposures for a four-day period. The affinity of the chemicals to SC
      and their gradual accumulation in the skin in the present study is the probable
      cause for the differences in the skin irritation profiles of different aliphatic
      chemicals. The findings of the present study will be helpful in understanding the
      skin irritation response of the chemicals in humans; indeed the reality check
      arises from dermal exposures in humans and human experience in occupational
      handling of these chemicals.

PMID- 15941008
TI  - Effect of Mentha piperita (Labiatae) and Mentha spicata (Labiatae) on iron
      absorption in rats.
AB  - AIM: The effect of Mentha piperita (Labiatae) and Mentha spicata (Labiatae) teas,
      which contain different phenol compounds, on iron metabolism was studied. These
      teas grow in different areas of the city of Isparta, Turkey. These herbals were
      given to the rats in tea. METHODS: Forty-eight male Wistar albino rats weighing
      200-250 g were used for this study. The rats were divided into four groups of 12
      animals: Group I received no herbal tea (control group); Group II received 20 g/L
      M. piperita tea; Group III received 20 g/L M. spicata tea; Group IV received 40
      g/L M. spicata tea. Herbal teas were prepared daily and provided at all times to
      the rats over 30 days as drinking water. RESULTS: M. piperita tea caused a
      decrease in serum iron and ferritin levels (P < 0.05), and caused an increase in
      unsaturated iron-binding capacity (UIBC) (P < 0.01). M. spicata tea caused no
      significant change in serum iron, ferritin levels and UIBC (P > 0.05).
      CONCLUSION: Both herbal teas inhibited Fe absorption. Inhibition caused by M.
      spicata tea was dose dependent. Therefore, when drinking these teas, their effect
      should be considered, especially for children and anemic patients.

PMID- 15941009
TI  - Morphometric analysis of mice uteri treated with the preservatives methyl, ethyl,
      propyl, and butylparaben.
AB  - The alkyl esters of p-hydroxybenzoic acid (PHBA) known as parabens (Pbens) are
      widely used as preservatives in food, pharmaceuticals, and cosmetics. Several in
      vivo and in vitro studies have shown these compounds to be estrogenic. Here, for
      the first time, we present evidence of their estrogenicity using a morphometric
      analysis of uteri from mice treated with the preservatives methylparaben
      (MePben), ethylparaben (EtPben), propylparaben (PrPben), and butylparaben
      (BuPben) compared with estradiol (E2). Different groups of adult ovariectomized
      (Ovx) CD1 mice were subcutaneously (sc) treated daily for three days with two
      different equimolar doses (362 and 1086 micromol/kg) of the Pbens: MePben (55 and
      165 mg/kg), EtPben (60 and 180 mg/kg), PrPben (65 and 195 mg/kg), BuPben (70 and
      210 mg/kg), E2 (10 microg/kg; 0.036 micromol/kg), and vehicle (propyleneglycol;
      V, 10 mL/kg). On the fourth day, uteri were dissected, blotted, weighed, and
      placed in a fixative solution for 24 h. The paraffin embeded uteri were cut to
      obtain 7 microm thick transversal sections. Luminal epithelium heights (LEH),
      glandular epithelium heights (GEH), and myometrium widths (MW) were measured. The
      highest Pbens dose was able to produce uterotrophic effects (38 to 76%) compared
      to E2 efects (100%). The relative uterotrophic potency to E2 (100) was from 0.02
      to 0.009. Significant increases (P < 0.05) in LEH, GEH, and MW as compared with V
      were obtained: LEH from 87 to 113% (E2 153%), GEH from 10 to 40% (E2 60%), and MW
      from 35 to 43% (E2 88%). These results confirm that Pbens at the doses assayed
      here induce estrogenic histological changes in the uteri of Ovx mice.

PMID- 15941010
TI  - Prevention of mobile phone induced skin tissue changes by melatonin in rat: an
      experimental study.
AB  - Most of the mobile phones in Turkey emit 900 MHz radiation which is mainly
      absorbed by the skin and, to a lesser extent, muscle. The aim of this study was
      to investigate the effects the 900 MHz electromagnetic irradiation emitted by
      these devices on the induction of histopathologic changes in skin and the effect
      of melatonin (Mel) on any of these changes. Thirty male Wistar-Albino rats were
      used in the study. The experimental groups were composed of: a nontreated control
      group, an irradiated group (IR) without Mel and an irradiated with Mel treatment
      group (IR + Mel). 900 MHz radiation was applied to IR group for 10 days (30
      min/day). The IR + Mel group received 10 mg/kg per day melatonin in tap water for
      10 days before irradiation. At the end of the tenth day, the skin graft was
      excized from the thoraco-abdominal area. Histopathologic changes in skin were
      analyzed. In the IR group, increased thickness of stratum corneum, atrophy of
      epidermis, papillamatosis, basal cell proliferation, increased granular cell
      layer (hypergranulosis) in epidermis and capillary proliferation, impairment in
      collagen tissue distribution and separation of collagen bundles in dermis were
      all observed compared to the control group. Most of these changes, except
      hypergranulosis, were prevented with melatonin treatment. In conclusion, exposure
      to 900 MHz radiation emitted by mobile phones caused mild skin changes.
      Furthermore, melatonin treatment can reduce these changes and may have a
      beneficial effect to prevent 900 MHz mobile phone-induced rat skin changes.

PMID- 15941011
TI  - Protective effects of erdosteine on rotenone-induced oxidant injury in liver
      tissue.
AB  - Rotenone, an insecticide of botanical origin, causes toxicity through inhibition
      of complex I of the respiratory chain in mitochondria. This study was undertaken
      to determine whether rotenone-induced liver oxidant injury is prevented by
      erdosteine, a mucolytic agent showing antioxidant properties. There were four
      groups of Male Wistar Albino rats: group one was untreated as control; the other
      groups were treated with erdosteine (50 mg/kg per day, orally), rotenone (2.5
      mg/mL once and 1 mL/kg per day for 60 days, i.p.) or rotenone plus erdosteine,
      respectively. Rotenone treatment without erdosteine increased xanthine oxidase
      (XO) enzyme activity and also increased lipid peroxidation in liver tissue (P <
      0.05). The rats treated with rotenone plus erdosteine produced a significant
      decrease in lipid peroxidation and XO activities in comparison with rotenone
      group (P < 0.05). Erdosteine treatment with rotenone led to an increase in
      catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the
      rotenone group (P < 0.05). There was no significant difference in nitric oxide
      (NO) level between groups. There were negative correlations between CAT activity
      and malondialdehyde (MDA) level (r = -0.934, P < 0.05) with between CAT and SOD
      activities (r = -0.714, P < 0.05), and a positive correlation between SOD
      activity and MDA level (r = 0.828, P < 0.05) in rotenone group. In the rotenone
      plus erdosteine group, there was a negative correlation between XO activity and
      NO level in liver tissue (r = -0.833, P < 0.05). In the light of these findings,
      erdosteine may be a protective agent for rotenone-induced liver oxidative injury
      in rats.

PMID- 15941012
TI  - Human health risk assessment of 2-mercaptobenzothiazole in drinking water.
AB  - 2-Mercaptobenzothiazole (MBT) is used as a vulcanization accelerator in rubber
      products that come into contact with potable drinking water. When such products
      are evaluated for contact with potable water and submitted for ANSI/NSF Standard
      61 certification, any chemical extracting from these products must be below an
      appropriate action level of exposure. As defined by Standard 61, a total
      allowable concentration (TAC) is the maximum concentration of a nonregulated
      contaminant allowed in a public drinking water supply, and the single product
      allowable concentration (SPAC) is 10% of the TAC. Currently, MBT has a TAC of 40
      microg/L and a SPAC of 4 microg/L. A comprehensive health effects evaluation of
      MBT was performed to determine whether these action levels should be revised.
      Epidemiological investigations indicate that workers occupationally exposed to
      MBT have an increased risk of death from bladder cancer. Genotoxicity
      investigations in bacterial and mammalian test systems provide some evidence
      indicating that MBT has the potential to induce mutations and chromosomal
      aberrations. Toxicity studies in rats and mice chronically exposed to MBT
      identified increases in various tumours, such as adrenal gland tumours, pituitary
      gland tumours, liver tumours and renal pelvis tumours. The biological
      significance of most of these tumours is questionable due to a variety of
      factors, such as a lack of dose-response between tumour incidence and dose, and
      the effect of test article vehicle (corn oil) upon tumour rates. Potential human
      health effects of exposure to MBT can be predicted from an NTP 2-year cancer
      study in rats, as well as epidemiological investigations in occupationally
      exposed workers. A comprehensive review of the epidemiological and toxicological
      dataset for MBT indicates that the induction of renal pelvis transitional cell
      tumours is the most sensitive and relevant health effects endpoint upon which to
      base a revised TAC and SPAC. A multistage model was used to extrapolate to low
      dose MBT exposures due to the genotoxicity and clastogenicity of MBT. A TAC of
      600 microg/L was derived for MBT, and was based upon an LED10 of 157.681 mg/kg
      per day. A SPAC of 60 microg/L was derived by multiplying the revised TAC by
      0.10, and rounding to one significant figure. These revised action levels are
      based upon the most sensitive health effects endpoint, as well as current cancer
      risk assessment methodology.

PMID- 15941013
TI  - Occupational exposure limits in the context of solvent mixtures, consumption of
      ethanol, and target tissue dose.
AB  - Individuals are exposed to mixtures, and never to single chemicals. Depending on
      the composition of the elements of mixtures, significant toxicological
      interactions between the components may occur. These interactions are complex and
      often difficult to predict, ranging from synergistic to additive and subadditive
      interactions. The nature of the interactions needs to be evaluated as the target
      tissue dose of the active form of each chemical. PBPK modeling is an effective
      tool for determining the target tissue dose and evaluating these interactions
      when data are available for model development. Some of the interactions are
      pharmacokinetic in nature, affecting the disposition of other chemicals in the
      body. Other interactions can be pharmacodynamic in nature, altering the effects
      that other chemicals have on the organism. For many organic solvents, these
      interactions occur principally at the level of the metabolizing enzyme,
      cytochrome P-450 2E1 (CYP2E1). Many solvents are known to induce or inhibit
      CYP2E1, or both. Mixtures may be comprised of concomitant exposures to chemicals
      or from components encountered separately on-the-job, off-the-job, through the
      diet, and otherwise. Examples of mixtures where the exposure to separate
      components occurs off the job will be discussed, with special emphasis on ethanol
      consumption as a modifier of solvent pharmacokinetics. The present practice of
      the linear extrapolation of the toxicity of individual mixture components in the
      interpretation of occupational exposure limits will also be critiqued.

PMID- 15941015
TI  - Food quality and safety: traceability and labeling.
AB  - This article discusses food systems in general, their development over the past
      120 years, and realities and problems faced by a world population of over 6
      billion people. Various food and feed problems are mentioned, and the concept of
      "traceability" is discussed in the context of the broader and more useful
      approach of using "good practices" at all levels of the food chain.

PMID- 15941014
TI  - Updated knowledge about the presence of phenolic compounds in wine.
AB  - Phenolic compounds are partly responsible for the color, astringency, and
      bitterness of wine, as well as for numerous physiological properties associated
      with wine consumption. Mass spectrometry has allowed for great progress in the
      identification and characterization of wine polyphenols. The aim of the present
      article is to summarize the numerous advances recently achieved in this field.
      The main type of phenolic compounds found in wine, including hydroxybenzoic and
      hydroxycinnamic acids, stilbenes, flavones, flavonols, flavanonols, flavanols,
      and anthocyanins, are firstly described. Chemical reactions and mechanisms
      involving phenolic compounds during winemaking are also extensively discussed,
      including enzymatic and chemical oxidation reactions, direct and acetaldehyde
      mediated anthocyanin-tannin condensation reactions, acetaldehydemediated and
      glyoxylic acid-mediated tannin-tannin condensation reactions and, C-4/C-5
      anthocyanin cycloaddition reactions with 4-vinylphenols, vinylflavanols and
      pyruvic acid, among others, leading to the formation of pyranoanthocyanins.
      Useful mass spectral data of well-known and novel phenolic compounds recently
      identified in wine, and details related to their fragmentation pathway according
      to different ionization techniques, are given.

PMID- 15941016
TI  - Membrane cleaning in the dairy industry: a review.
AB  - Membrane separation processes have become part of the set of basic unit
      operations for dairy process design and product development. These processes are
      employed in a variety of separation and concentration duties, but in all cases,
      the membranes must be cleaned regularly to remove both organic and inorganic
      material deposited on the surface from the fluid stream being processed. Cleaning
      is a vital step in maintaining the permeability and selectivity of the membrane
      and is necessary to return the plant to its original capacity, to minimize risks
      of bacteriological contamination, and to produce acceptable products. Caustic-,
      acidic-, and enzyme-based cleaners may be used for membrane cleaning and are
      usually formulated with additives to best match the specific cleaning duty.
      Cleaning generates significant volumes of wastewater and reduces membrane life
      and plant productivity, so each regime must be optimized with respect to
      concentration, order and duration of cleaning steps, temperature, pressure, and
      flow rate. This article reviews the key mechanisms governing cleaning performance
      and suggests directions by which further optimization may be achieved.

PMID- 15941017
TI  - Role of the conjugated linoleic acid in the prevention of cancer.
AB  - There are multiple lines of evidence that a variety of natural fatty acids are
      effective in health promotion. Among these fatty acids, conjugated linoleic acid
      (CLA)--a collective term referring to a mixture of positional and geometric
      isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic acid)--is currently
      under intensive investigation due to its health-promotion potential. The
      antitumor activity of CLA is of special interest, since it shows inhibitory
      effects against multistage carcinogenesis at relatively low dietary levels. Many
      studies using in vivo and in vitro models have shown that CLA suppresses the
      development of multistage carcinogenesis at different sites. The research to date
      on CLA has provided a vast amount of information about the mechanism on how CLA
      functions in the prevention of cancer. This article discusses characteristics of
      CLA in the prevention of cancer in both in vivo and in vitro studies and the
      possible underlying chemoprevention mechanisms.

PMID- 15941018
TI  - Editorial: Mental disability.

PMID- 15941020
TI  - Rehabilitation of the disabled mentally III in the community.
AB  - The purpose of this article is to review the latest developments in the area of
      rehabilitation of disabled mentally ill patients. Rehabilitation is a
      comprehensive and multi-disciplinary treatment. It involves a wide variety of
      interventions. These interventions are designed to enable the client to integrate
      into the normal life of the community and to improve his quality of life. This
      review discusses the different approaches and their effectiveness. The approaches
      that are described include comprehensive psychiatric, psycho-social and psycho
      educational interventions including family therapy, training in social skills,
      and vocational intervention in programs and services in the community. The
      approaches that have been shown to be the most effective in controlled studies
      include: follow-up psychiatric drug treatment, individual and family psycho
      educational treatment; social skills training; community sheltered-housing
      facilities and vocational rehabilitation programs. It has been emphasized that
      the effectiveness of treatment is conditional not only on the client's resilience
      and a comprehensive and multidisciplinary treatment approach, but also on the
      community financial resources and the level of training of the professionals.

PMID- 15941019
TI  - The contribution of social disability to the evaluation of mental disability
      among PTSD veterans.
AB  - BACKGROUND: Israeli veterans who claim for recognition of their mental disability
      and compensation undergo multi-professional assessments including a detailed
      psychosocial evaluation. OBJECTIVES: To conduct a systematic evaluation of the
      social disabilities of veterans with PTSD; to examine the relationships between
      the various aspects of their social disability and their PTSD symptom severity,
      on the one hand, and the ratings they receive from psychiatrists determining
      their overall disability, on the other hand. METHOD: The study was conducted on
      120 veterans with PTSD, all filing for compensation. Data was collected by means
      of semi-structured interviews that were carried out by social workers in ajoint
      meeting with the veterans and their spouses and that covered marital, parental
      and social functioning; from the self-report PTSD questionnaire that the veterans
      filled out; and from the final disability ratings in the veterans' files.
      RESULTS: Findings showed a disturbing picture of impaired marital, parental and
      social functioning of veterans with PTSD. In addition, they indicate that both
      PTSD severity and the psychiatrists' disability ratings were correlated with only
      a quarter or so of the veterans' specific social disabilities in the areas
      studied. DISCUSSION: Several explanations for the pattern of correlations between
      these two assessments are offered. In addition, we highlight the importance of a
      sensitive and detailed evaluation of social disability as well as recommending
      the development of practical guidelines for the determination of disability.

PMID- 15941021
TI  - Dementia and disability in old-age: a clinical perspective.
AB  - This article briefly reviews the subject of disability in elderly dementia
      patients, and focuses primarily on the clinical perspective. The prevalence of
      dementia among community-dwelling elderlies is estimated to be about 5% and
      increases with age. Disability due to cognitive impairment and dementia is
      frequent in this group. Clinical determinants of disability in dementia include:
      a) Diagnosis of dementia: disability is inherent to the diagnosis of dementia
      even though the term is not specified in modern psychiatric classifications; b)
      Severity of dementia: expressed by breakdown into stages or by providing a
      psychometric score; c) Neuropsychological correlates of performance; d)
      Associated psychopathology; e) Etiology of dementia; f) Associated impairment in
      health or physical handicap. Finally, some management principles of disability in
      dementia are considered.

PMID- 15941022
TI  - Evaluation of psychiatric disability in PTSD of military origin.
AB  - BACKGROUND: Israeli veterans suffering from post-traumatic stress disorder (PTSD)
      filed claims for recognition of their mental disability and for compensation
      underwent thorough psychiatric evaluations conducted by an interdisciplinary
      team. OBJECTIVE: To study the clinical features and functional impairment of PTSD
      veterans who filed claims for psychiatric disability. To evaluate possible
      relationships among severity of PTSD, psychiatric comorbidity and level of
      disability. METHOD: Subjects were 294 veterans with PTSD. Evaluation included a
      semi-structured psychiatric interview; self report questionnaires of PTSD,
      psychiatric symptoms and assessment of functional impairments (in self-care in
      daily living, interpersonal--familial and social, and occupational functioning).
      Upon completion of the various assessments the psychiatrist determined a global
      disability score. RESULTS: 156/294 (53%) of the PTSD subjects had psychiatric
      comorbidity, mainly depression (31%) and anxiety (15%). PTSD casualties suffered
      significant functional impairments, more in occupational functioning than
      interpersonal and activities of daily living, respectively. A number of PTSD
      symptoms were positively correlated with functional impairments in the
      occupational and interpersonal areas and with the global disability score, while
      psychiatric comorbidity was not. CONCLUSION: PTSD veterans who file for
      psychiatric disability report severe mental distress and functional impairment,
      and probably constitute the more severe PTSD casualties. Systematic assessment of
      functional impairment in addition to clinical examination is needed for valid
      evaluation of disability and for determining disability score.

PMID- 15941023
TI  - Legal aspects of work-related mental illness and disorder.
AB  - Workers' compensation laws exist to compensate workers for injuries sustained on
      the job. In Israel, this includes mental as well as physical injuries, both
      generally described by the law as "work accidents." Courts readily accept mental
      injuries as work-related when they are caused by physical work events. In cases
      where a physical event precipitates mental injury, courts allow presumptions of
      work-relatedness as proof of part of the case. However, when a psychological
      event causes a psychological illness (referred to as "purely psychological"
      cases), courts must grapple with ascertaining whether these non-visible, internal
      events, often accompanied by multiple causes, have the requisite work connection
      to justify compensation. Ultimately, a court requires proof of each aspect of a
      purely psychological case to assure itself of the legitimacy of the claim. To
      provide courts with requisite proof of work-relatedness, a claimant in a purely
      psychological case must show that the event was sudden, unexpected, severe, and
      that it was caused in significant part by work, as viewed objectively, rather
      than on the basis of a claimant's subjective perception of reality. Gradual
      events, such as repetitive work stress, are generally not compensated.
      Presumptions of work-relatedness will not apply. The workers' compensation system
      cannot bear the burden for psychological events that occur as a usual part of the
      work environment or that are the result of multiple non-work-related causes.

PMID- 15941024
TI  - Trauma and traumatized populations in Israel: the Israel Journal of Psychiatry
      and Related Sciences, 1963-2002.
AB  - In Europe and the U.S., awareness of interpersonal traumatization has disappeared
      and reappeared, seemingly connected to socio-historical conditions. The authors
      wanted to explore this phenomenon in Israel, a complex, multicultural, society
      that has yet to know peace. Content analysis of a professional journal, the
      Israel Journal of Psychiatry, was the method of choice. This journal has existed
      since the fifteenth year of Israel's existence and, because it is published in
      English, is in active dialogue with the rest of the world. Striking parallels
      were found between the timing and focus on traumas in the published articles and
      the socio-cultural context.

PMID- 15941025
TI  - Forensic psychiatry corner 3--the issue of anonymity in lay referrals.

PMID- 15941026
TI  - Does pretreatment insomnia or anxiety predict acute response to bupropion SR?
AB  - BACKGROUND: This retrospective analysis was conducted to determine whether
      pretreatment levels of insomnia or anxiety were associated with likelihood of or
      time to antidepressant response with bupropion sustained release (SR). METHODS:
      Data from an open-label, 8-week, acute phase multicenter study of 797 adult
      outpatients with recurrent, nonpsychotic major depressive disorder who received
      bupropion SR (300 mg/day) were used. Depressive symptom severity was measured by
      the 17-item Hamilton Rating Scale for Depression (HAM-D17), insomnia by totaling
      the three HAM-D17 insomnia items (early, middle, late), and anxiety by the 14
      item Hamilton Rating Scale forAnxiety. RESULTS: Overall, 67% (533/797) of
      patients responded (defined as > or = 50% reduction in baseline HAM-D17). Neither
      baseline insomnia nor baseline anxiety was related to the likelihood of achieving
      response. Higher baseline insomnia and lower baseline anxiety were associated
      with an earlier onset of response (about one week sooner in each). CONCLUSIONS:
      Predicting the likelihood of antidepressant response with bupropion SR cannot be
      based on either baseline insomnia or anxiety levels.

PMID- 15941027
TI  - Variable effects of psychosocial factors on the clinical course of schizophrenia.
AB  - BACKGROUND: Recent work suggests that psychosocial stress factors play a lesser
      role (qualitatively) in the progression of schizophrenic illness in male
      patients. The authors endeavored to determine if hospitalization in schizophrenic
      patients of both sexes is associated with less quantifiable psychosocial stress
      over time. METHODS: Male and female, schizophrenic inpatients from 2 urban
      centers in New York State (n = 31) were enrolled in this retrospective and cross
      sectional study. Linear regression analysis was performed with illness duration
      as the independent variable and ln (1 + Paykel Life Events Schedule) score,
      associated with current hospitalization, as the dependent variable. RESULTS:
      Linear regression analysis revealed an inverse relationship (slope = -.086) that
      was statistically significant (p < .01). This result indicates an annual 92%
      reduction in the psychosocial stress load associated with hospitalization. The
      inverse relationship remained intact when males and females were analyzed
      separately. CONCLUSIONS: The data suggest that, over time, male and female
      patients with schizophrenia experience hospitalization and, likely, relapse as
      well in response to less of a total significance load of psychosocial stress.

PMID- 15941028
TI  - Are SSRIs really more effective for anxious depression?
AB  - BACKGROUND: Selective Serotonin Reuptake Inhibitors (SSRIs) are well-established
      first-line agents for Anxiety Disorders. Anxiety is also a frequent manifestation
      of major depression. Many psychiatrists assume that anxious depression is more
      responsive to SSRIs than to other antidepressants. The purpose of this literature
      review was to determine if SSRIs or any other antidepressants are superior.
      METHODS: A computerized search was conducted of double-blind, English-language
      studies comparing antidepressants available in the United States. Databases
      searched included Medline and PsycINFO. RESULTS: SSRIs were not found to be
      superior to other antidepressants in the treatment of anxious depression.
      CONCLUSIONS: The above assumption is not supported. Treatment implications are
      discussed.

PMID- 15941029
TI  - Current patterns and future directions in the treatment of insomnia.
AB  - BACKGROUND: Despite the high prevalence and the high burden associated with
      chronic insomnia, it remains largely unrecognized and often inadequately treated
      by physicians. METHODS: A review was undertaken of the literature on barriers to
      both acute and chronic treatment of insomnia, as well as recent trials of
      pharmacologic and nonpharmacologic agents for insomnia. RESULTS: Obstacles to
      appropriate treatment of the condition include outdated insomnia management
      guidelines, which have contributed to US Food and Drug Administration
      restrictions on longer-term prescription of hypnotic agents; lack of research
      demonstrating the benefit of treating insomnia; and fears of tolerance and
      withdrawal effects of long-term use of hypnotic agents, as well as an absence of
      longer-term, randomized, controlled, double-blind trials of existing agents used
      to treat insomnia. CONCLUSIONS: There is evidence that improved sleep may improve
      outcome in some medical and psychiatric illnesses. Both behavioral and
      pharmacologic therapies have shown efficacy in chronic insomnia. In addition, a
      recent 6-month, randomized, controlled study has demonstrated that at least one
      agent may be safe and effective in longer-term use.

PMID- 15941030
TI  - The diagnosis of borderline personality disorder: problematic but better than the
      alternatives.
AB  - BACKGROUND: The purpose of this review is to examine empirical evidence
      concerning critiques of the diagnosis of borderline personality disorder (BPD):
      for uncertain validity, and for overlap with other mental disorders. METHODS: A
      review of the literature on the validity and comorbidity of BPD was conducted.
      RESULTS: Since BPD is a complex multidimensional construct, its validity is
      inevitably problematic, but no more so than most other psychiatric diagnoses. The
      comorbidity of BPD is probably an artefact of the current classification system,
      and there is no convincing evidence that BPD is a variant of an Axis I disorder.
      CONCLUSIONS: Although further research should lead to changes in classification,
      the diagnosis of BPD retains significant clinical utility.

PMID- 15941031
TI  - Auditory and visual P300 evoked potentials do not predict response to valproate
      versus lithium in patients with mania.

PMID- 15941032
TI  - Simultaneous determination of thyreostatic residues in animal tissues by matrix
      solid-phase dispersion and gas chromatography-mass spectrometry.
AB  - A method for determination of thyreostatic residues in animal tissues by matrix
      solid-phase dispersion (MSPD) and gas chromatography-mass spectrometry in
      selected ion detection mode was developed. Thyreostatic compounds in different
      matrices were extracted and purified by combination of MSPD and subsequent solid
      phase extraction. Silica gel was selected as the solid support of both procedures
      and the conditions of the procedures were optimized. Thyreostats were derivatized
      with pentafluorobenzylbromide (PFBBr) in strong basic medium and then with N
      methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA), which can improve the
      yields of derivatization for thyreostats, the repeatability, and therefore the
      limits of detection (LOD) of thyreostats. The limits of detection reached 10
      microg/kg (2-thiouracil, 6-methyl-2-thiouracil and 6-propyl-2-thiouracil), 20
      microg/kg (6-phenyl-2-thiouracil) and 50 microg/kg (tapazole) with high
      recoveries (more than 70% for most of thyreostats) and relative standard
      deviations between 4.5% and 8.7%.

PMID- 15941033
TI  - Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid
      phase microextraction coupled to high performance liquid chromatography and
      analysis of amphetamines in urine samples.
AB  - In-tube solid-phase microextraction (SPME) based on a poly(methacrylic acid
      ethylene glycol dimethacrylate) monolithic capillary column was investigated for
      the extraction of amphetamine, methamphetamine and their methylenedioxy
      derivatives. The monolithic capillary column showed high extraction efficiency
      towards target analytes, which could be attributed to its larger loading amount
      of extraction phase than conventional open-tubular extraction capillaries and the
      convective mass transfer procedure provided by its monolithic structure. The
      extraction mechanism was studied, and the results indicated that the extraction
      process of the target analytes was involved with hydrophobic interaction and ion
      exchange interaction. The polymer monolith in-tube SPME-HPLC system with UV
      detection was successfully applied to the determination of amphetamine,
      methamphetamine and their methylenedioxy derivatives in urine samples, yielding
      the detection limits of 1.4 - 4.0 ng/mL. Excellent method reproducibility (RSD <
      2.9%) was found over a linear range of 0.05-5 microg/mL, and the time for the
      whole analysis was only approximately 25 min. The monolithic capillary column was
      reusable in coping with the complicated urine samples.

PMID- 15941034
TI  - Azithromycin extraction from municipal wastewater and quantitation using liquid
      chromatography/mass spectrometry.
AB  - Azithromycin is a broad spectrum antimicrobial agent that is approved in the
      United States for use in humans. Due to azithromycin's low rate of metabolism it
      is likely to be found in wastewater treatment plants, where its broad spectrum of
      antimicrobial activity could lead to development of resistance in bacteria. A
      liquid-liquid extraction using K2CO3 and methyl-t-butyl ether (MTBE) was used to
      extract azithromycin from 10 ml aliquots of wastewater. Liquid chromatography was
      performed using a Luna C18(2) (30 mm x 2.0 mm) column with a mass spectrometer
      friendly mobile phase containing 50:24:2:24 acetonitrile, methanol,
      tetrahydrofuran, and 0.04 M ammonium hydroxide. The mass spectrometer used an
      electrospray source with positive ionization and an ion trap detector. A linear
      standard curve from 5 to 200pg/ml was validated and used to quantitate
      azithromycin in wastewater.

PMID- 15941035
TI  - Optimization of intracellular microcystin extraction for their subsequent
      analysis by high-performance liquid chromatography.
AB  - Microcystins are a family of heptapeptide hepatotoxins produced by some genera of
      cyanobacteria. These toxins have been responsible for the illness and death of
      both animals and humans. Due to their hazard to human health, extraction of all
      intracellular microcystin variants is required to characterize and quantify all
      microcystins present in a sample. To date, there is little work reported
      comparing results obtained with different extraction methods. Findings reported
      to date indicate that selection of solvent will vary depending on sample and its
      microcystin contents. In the present work, a wide range of extraction volumes and
      solvents were evaluated over a range of pH and extraction times in order to
      optimize a suitable method for the extraction of a wide range of microcystins.
      The number of extractions required was also studied. This study was carried out
      using mainly two laboratory cultures which contain microcystin variants with
      quite different hydrophobicities. This is the first time that the most commonly
      used solvents for intracellular microcystin extraction have been studied in
      detail.

PMID- 15941036
TI  - Conformational order of n-alkyl modified silica gels as evaluated by Fourier
      transform infrared spectroscopy.
AB  - The conformational behaviour of non-deuterated and selectively deuterated alkyl
      modified silica gels in the dry state is examined by variable temperature FT IR
      spectroscopy. In the present study, three systems are considered, which are
      distinguished by the length of the tethered alkyl chains (C9Hl9-, C18H37-, C22H45
      ). The desired information is obtained by the analysis of various conformational
      sensitive IR bands, including CH2 wagging, CD2 stretching and CD2 rocking bands.
      The analysis of the CH2 wagging bands provides the relative amounts (i.e.,
      integral numbers over the whole chain) of the kink/gauche-trans-gauche, double
      gauche and end-gauche conformers in the tethered alkyl chains. From the analysis
      of the CD2 stretching and CD2 rocking bands information about the conformational
      order at a specific deuterated methylene segment is available. Here, the CD2
      rocking band data are used to determine the amount of gauche conformers at the
      deuterated carbon positions C-4 and C-6, and C-12. It is found that the
      conformational order critically depends on the actual alkyl chain length, chain
      position and sample temperature. Particular emphasis is given to the impact of
      the external pressure during sample preparation on the alkyl chain conformations,
      about which so far no information is available. It is observed that the samples
      prepared as KBr pellets, which experienced a pressure of about 10 kbar, are
      characterised by a lower amount of gauche conformers. This substantial increase
      of conformational order is attributed to better alkyl chain packing along with a
      gain of intermolecular chain interactions.

PMID- 15941037
TI  - Semi-industrial isolation of salicin and amygdalin from plant extracts using slow
      rotary counter-current chromatography.
AB  - Salicin in the bark extract of Salix alba and amygdalin in the fruit extract of
      Semen armeniacae were each separated by slow rotary counter-current
      chromatography (SRCCC). The apparatus was equipped with a 40-L column made of 17
      mm i.d. convoluted Teflon tubing. A 500g amount of crude extract containing
      salicin at 13.5% was separated yielding 63.5 g of salicin at 95.3% purity in 20h
      using methyl tert-butyl ether-l-butanol (1:3) saturated by methanol-water (1:5)
      as a stationary phase and methanol-water (1:5) saturated by methyl tert-butyl
      ether-1-butanol (1:3) as a mobile phase. A 400g amount of crude extract
      containing amygdalin at 55.3% was isolated to yield 221.2g of amygdalin at 94.1%
      purity in 19h using ethyl acetate-1-butanol (1:2) saturated by water as a
      stationary phase and water saturated by ethyl acetate-1-butanol (1:2) as a mobile
      phase. The flow rate of the mobile phase was 50 ml/min. The results show that
      industrial SRCCC separation of salicin and amygdalin is feasible using a larger
      column at a higher flow rate of the mobile phase.

PMID- 15941038
TI  - Improved assay for catechol-O-methyltransferase activity utilizing norepinephrine
      as an enzymatic substrate and reversed-phase high-performance liquid
      chromatography with fluorescence detection.
AB  - We have previously established a rapid catechol-O-methyltransferase (COMT) assay
      using norepinephrine (NE) as a natural substrate and flow-injection analysis. In
      this study, the method is improved for screening of COMT inhibitors or activators
      using reversed-phase high-performance liquid chromatographic separation with
      fluorescence detection. The excess substrate, NE, was removed by the addition of
      borate in the eluent for HPLC to make an ionic complex with NE, which was eluted
      faster than the enzymatic product, normetanephrine. The method had good precision
      and accuracy, and was able to assay one sample in 5 min, showing the usability
      for screening of COMT inhibitors or activators.

PMID- 15941039
TI  - Estimation of diffusion parameters in functionalized silicas with modulated
      porosity. Part I: chromatographic studies.
AB  - The diffusion parameters of binary gas mixture He (tracer gas)-N2 (carrier gas)
      in hybrid organic-inorganic SiO2-X porous solids which have suffered gradual
      functionalization with functional groups X of increasing length (X = psi, [triple
      bond]Si-H, [triple bond]Si-CH2OH, [triple bond]Si-(CH2)3OH, [triple bond]Si
      (CH2)11CH3) are reported. The effective diffusivities Deff, the Henry law
      constants K as well as the tortuosity factors tau for the examined solids were
      estimated by a typical pulse gas chromatographic method. Analysis of the
      experimental results was carried out by the well-known method of linearization of
      moments. The moments s analysis provides a powerful means for extracting
      diffusion parameters from the experimental response curves The proposed
      methodology is simple compared to other similar studies and provides rapidly
      reliable data. The results of this work indicate that the effective diffusivity
      Deff in porous networks drops markedly as the initial porosity of the parent SiO2
      sample is blocked by the functionalization of the pore surfaces with functional
      groups of increasing size, [triple bond]Si-H, [triple bond]Si-CH2OH, [triple
      bond]Si-(CH2)3OH and [triple bond]Si-(CH2)11CH3. The low values of the Henry law
      constants K found indicate that the adsorption of He on the porous surfaces for
      all the solids is weak. Also, the tortuosity factor r is proportionally
      correlated to the pore blocking effects and the percolation phenomena of gases
      flowing into the porous network.

PMID- 15941040
TI  - Estimation of diffusion parameters in functionalized silicas with modulated
      porosity. Part II: pore network modeling.
AB  - In this work, the pore structure of those five (5) silicas SiO2-X (see Part I)
      which have suffered gradual functionalization with functional groups X of
      increasing length (X = psi, [triple bond]Si-H, [triple bond]Si-CH2OH, [triple
      bond]Si-(CH2)3OH, [triple bond]Si-(CH2)11CH3), is modeled as a three-dimensional
      cubic network of cylindrical pores. Those hybrids organic-inorganic SiO2-X
      samples are characterized by different extent of pore blocking effects. The pores
      of samples are represented in a 9 x 9 x 9 lattice by the nodes as well the bonds
      that are interconnected in a so-called dual site-bond model, DSBM, network. The
      pore network is developed using a Monte Carlo statistical method where the
      cylindrical pores (nodes and bonds) are randomly assigned into the lattice, until
      matching of the theoretical results to the experimental data of N2 adsorption
      desorption measurements. Thus, a visual picture of the porous solid is possible.
      This realistic network is used next in order to study the steady-state gas
      transport (Knudsen gas-phase and viscous diffusion) properties for the examined
      materials and how flow processes depend on the morphology of the pore structure.
      The pore diffusivity Dp and total permeability P of each porous medium is
      determined based on theoretical calculations and the structural statistical
      parameters, such as porosity epsilonp, tortuosity factor tau and connectivity c
      of pores is discussed with the corresponding experimental data described in Part
      I of this work. The results indicate clearly that the diffusion model made it
      possible to predict pore effective diffusivity in these porous media in very good
      agreement with the corresponding experimental results for all the examined solids
      (Part I). The pore diffusivity increases significantly as the value of the pore
      connectivity increases but the transport properties of the network are influenced
      strongly at lowest connectivity. Also the predicted tortuosity factor is related
      inversely to the extent of interconnection of pores in these solids, which
      indicates that the influence of pore branching to the tortuosity factor of the
      pore network decreases, as connectivity increases.

PMID- 15941041
TI  - Retention behavior of small polar compounds on polar stationary phases in
      hydrophilic interaction chromatography.
AB  - Retention characteristics of four polar stationary phases (i.e., amide, amino,
      silica and sulfobetaine) were studied by using a group of small polar compounds
      in hydrophilic interaction chromatography (HILIC). Different polar stationary
      phases shared certain degrees of similarity, but also exhibited differences in
      retentivity and selectivity for the model compounds. Among the four columns
      studied, HILIC Silica column had the least retention for the model compounds, but
      also showed different selectivity from other three columns. Experimental data
      also provided some evidences that functional groups on the stationary phases
      might have certain degrees of influence on selectivity possibly through secondary
      interactions with the model compounds. The retention of the acids on the amino
      phase decreased with increasing salt concentration in the mobile phase due to the
      ion-exchange effect, and the retention process was endothermic as opposed to
      exothermic on other phases. This study also systematically investigated the
      effect of various experimental factors on the retention of the polar stationary
      phases, such as acetonitrile content, column temperature, buffer pH, salt type
      and concentration in the mobile phase.

PMID- 15941042
TI  - Development of a triple hyphenated HPLC-radical scavenging detection-DAD-SPE-NMR
      system for the rapid identification of antioxidants in complex plant extracts.
AB  - A rapid method for the simultaneous detection and identification of radical
      scavenging compounds in plant extracts was developed by combining an HPLC with on
      line radical scavenging using DPPH* as a model radical and an HPLC-DAD-SPE-NMR
      system. Using this method a commercial rosemary extract was investigated. All
      major compounds present in the extract were collected on SPE cartridges after
      their separation. Advantages of on-line SPE peak trapping are the possibility to
      perform HPLC with non-deuterated solvents, a concentration effect and being able
      to record NMR spectra in pure 100% deuterated solvents. After comparing DAD and
      DPPH scavenging chromatograms, 1H NMR spectra of compounds having radical
      scavenging activities were recorded. Afterwards all compounds were collected and
      infused into an ESI-MS. The five main active compounds - carnosol, carnosic acid
      carnosaldehyde, 12-methoxycarnosic acid and epiisorosmanol could be identified
      from the combined UV, NMR and mass spectral data without actually isolating them.
      It was possible to record on-line an HMBC spectrum of carnosic acid. Also one
      compound was tentatively identified as epirosmanol methyl ether.

PMID- 15941043
TI  - Full verification of the liquid exclusion-adsorption chromatography theory using
      monolithic capillary columns.
AB  - Capillary electrochromatography (CEC) was used to separate alkyl phenol
      ethoxylates (APEs) as model diblock copolymers, with monolithic polymers as
      stationary phases. The order of elution indicate that the two polymer blocks
      follow distinct chromatographic modes: size-exclusion for the poly(oxyethylene)
      group and adsorption interaction for the alkyl part. Therefore, our experimental
      results were compared to the theory describing liquid exclusion-adsorption
      chromatography (LEAC). They were found in perfect agreement with the theory,
      which turned to be verified for the first time over the full range of polymer
      lengths.

PMID- 15941044
TI  - Isolation of carotenoids from plant materials and dietary supplements by high
      speed counter-current chromatography.
AB  - Methods for the isolation of lipophilic pigments from crude extracts of plant
      materials (spinach and sweet corn) by high-speed counter-current chromatography
      (HSCCC) were developed. Particular attention was given to (all-E)-lutein and (all
      E)-zeaxanthin. However, the concomitant pigments neoxanthin, violaxanthin and
      beta-carotene as well as chlorophylls a and b were also considered. Furthermore,
      for the first time dietary supplements containing lutein and zeaxanthin were also
      used as a source for the recovery of carotenoids. Due to their simple matrix
      (oily excipient in soft gelatine capsules), sample preparation was facilitated
      and consumption of solvents was minimized. The carotenoids were characterized by
      1H NMR spectroscopy, by LC/APcI-MS in the positive ionization mode, and by UV-vis
      spectroscopy. Data showed that the target compounds were of high purity (90 -
      93%). Lutein and zeaxanthin may be used as reference substances for analytical
      purposes.

PMID- 15941045
TI  - Isolation and purification of baicalein, wogonin and oroxylin A from the
      medicinal plant Scutellaria baicalensis by high-speed counter-current
      chromatography.
AB  - The medicinal plant Scutellaria baicalensis Georgi has been used widely in
      traditional Chinese medicine for anti-inflammation, anticancer, antiviral and
      antibacterial infections, reducing the total cholesterol level and decreasing
      blood pressures. A high-speed counter-current chromatography (HSCCC) method was
      developed for the preparative separation and purification of three bioactive
      flavonoids, namely, baicalein, wogonin and oroxylin A, from S. baicalensis
      Georgi. Preparative HSCCC with a two-phase solvent system composed of n-hexane
      ethyl acetate-n-butanol-water (1:1:8:10, v/v/v/v) was successfully performed by
      increasing the flow-rate of the mobile phase stepwise from 1.0 to 2.0 ml min(-1)
      after 4 h. The components purified and collected were analyzed by high
      performance liquid chromatography. The method yielded 144.8 mg of baicalein at
      95.7% purity, 50.2 mg of wogonin at 98.5% purity, and 12.4 mg of oroxylin A at
      93.2% purity from 500 mg of the crude extract in a one-step separation. The
      recoveries of baicalein, wogonin and oroxylin A were 92.7%, 91.6% and 92.5%,
      respectively.

PMID- 15941046
TI  - Preparative separation of isovitexin and isoorientin from Patrinia villosa Juss
      by high-speed counter-current chromatography.
AB  - High-speed counter-current chromatography (HSCCC) with a solvent system composed
      of ethyl acetate-n-butanol-water (2:1:3, v/v/v) was used to isolate and separate
      two C-glycosylflavones from Patrinia villosa Juss, a traditional Chinese
      medicine. The separation produced 42.9 mg isovitexin and 20.1 mg isoorientin with
      purities of 99.3% and 98.5%, respectively as determined by high-performance
      liquid chromatography (HPLC) in one step elution from 250 mg crude extract, and
      identification was performed by MS, 1H NMR and 13C NMR. It is the first report of
      discovering isovitexin and isoorientin from the plant of Patrinia genus.

PMID- 15941047
TI  - Orthogonality and similarity within silica-based reversed-phased chromatographic
      systems.
AB  - The starting point of this study was a current set of 32 chromatographic systems
      used to select initial conditions for method development to determine the
      impurity profile of a drug. The system exhibiting the best selectivity is then
      selected for further method development. In this current set eight silica-based
      phases are applied in conjunction with four mobile phases at different pH. In
      order to save time and resources, the possibilities for a meaningful subset
      selection were investigated. The most differing systems in terms of selectivity,
      in other words only the most orthogonal systems, need to be selected. Since the
      stationary phases are all silica-based, the selectivity differences are examined
      within a more homogeneous group than if, for instance, also zirconia- or polymer
      based columns would be involved. To select the subset of systems also the best
      overall separation performances are taken into account. The selection is based
      both on the HPLC-DAD data of a generic set of 68 drugs, and on the LC-MS-DAD
      results for a mixture of 15 drugs, less different in structure. The orthogonality
      is evaluated using weighted-average-linkage dendrograms and color maps, both
      created from the Pearson-correlation coefficients r between normalized retention
      times r. The Derringer's desirability functions are applied to define the systems
      with the best overall separation performances. Proposals for different
      representative subsets of the initial 32 systems are made.

PMID- 15941048
TI  - Analysis of trans-resveratrol by laser ionization mass spectrometry and HPLC with
      fluorescence detection. Comparison between both techniques.
AB  - A comparison between two analytical techniques is presented using trans
      resveratrol as analyte and vine leaf as sample. The employed methods were: (a)
      laser desorption followed by resonance enhanced multiphoton ionization coupled
      with time-of-flight mass spectrometry (LD-REMPI-TOFMS), and (b) reversed-phase
      high performance liquid chromatography (RP-HPLC) with fluorescence detection.
      While both techniques show a similar range of linearity and reproducibility,
      marked differences were found in their sensitivity and required time for a single
      analysis. For example: (i) the chromatographic method required considerable less
      time (30min) than the REMPI method to implement the analysis, (ii) the detection
      and quantification limits of the REMPI technique were 2.1 and 6.7 microg L(-1),
      respectively, while for the chromatographic method they were ten times minor,
      i.e. 20 and 67 microg L(-1), respectively. A critical assessment including
      advantages and drawbacks of each technique is presented.

PMID- 15941049
TI  - Preparative isolation and purification of alkaloids from the Chinese medicinal
      herb Evodia rutaecarpa (Juss.) Benth by high-speed counter-current
      chromatography.
AB  - High-speed counter-current chromatography (HSCCC) with a two-phase solvent system
      composed of n-hexane-ethyl acetate-methanol-water system (5:5:7:5, v/v) was
      applied to the isolation and purification of alkaloids from the Chinese medicinal
      plant Evodia rutaecarpa (Juss.) Benth. Five kinds of alkaloids were obtained and
      yielded 28 mg of evodiamine (I), 19 mg of rutaecarpine (II), 21 mg of evocarpine
      (III), 16mg of 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone (IV), 12
      mg of 1-methyl-2-dodecyl-4-(1H)-quinolone (V) from 180 mg of crude extract in a
      one-step separation, with the purity of 98.7%, 98.4%, 96.9%, 98.0%, 97.2%,
      respectively, as determined by high performance liquid chromatography (HPLC). The
      structures of these compounds were identified by 1H NMR and 13CNMR.

PMID- 15941050
TI  - Evaluation of a commercial immunoassay for the detection of chlorfenapyr in
      agricultural samples by comparison with gas chromatography and mass spectrometric
      detection.
AB  - A commercially available enzyme-linked immunosorbent assay (ELISA) kit with a
      high affinity monoclonal antibody was applied to residual analysis of insecticide
      chlorfenapyr in agricultural samples, and drawn a parallel between the ELISA and
      gas chromatography (GC) with mass spectrometry (MS). For standards prepared in
      water containing 5% (v/v) methanol, the sensitivity (I50 value), the dynamic
      range, and the limit of detection of the ELISA kit were 2.3, 1 - 10, and 0.1
      ng/g, respectively. The used monoclonal antibody in the ELISA kit had a high
      selectivity. The ELISA kit was applied to the determination of chlorfenapyr in
      two kinds of fruits (apple and peach). The examination of the influence of these
      matrices on the reliability of the assay performance indicated that the ELISA
      could determine it in these samples near the regulation values in Japan simply by
      diluting the methanolic extract or by concentrating it, without any clean-up
      procedures. Recovery and precision of the proposed ELISA method were assessed by
      fortifying fruit samples with chlorfenapyr ranging from 0.05 to 1.5 microg/g.
      Mean recoveries were 94.2 and 90.3% for apple and peach, and coefficients of
      variation were below 16% in most cases. The results obtained from the proposed
      ELISA method correlate well the reference GC/MS method for both fruit samples (r
      > 0.98). These considerations make the ELISA kit very useful analytical tool for
      monitoring and regulatory programs, without the need of complex and expensive
      instrumentation.

PMID- 15941051
TI  - Development of a high-sensitivity quantitative analytical method for determining
      polycarbamate by gas chromatography-mass spectrometry incorporating temperature
      programmable inlet on-column injection.
AB  - A highly sensitive analytical method was developed using GC/MS with temperature
      programmable inlet on-column injection (TPI on-column GC/MS) for determining
      methyl dimethyldithiocarbamate (DMDC-methyl) and dimethyl
      ethylenebisdithiocarbamate (EBDC-dimethyl), which are methyl derivatives of
      alkali decomposed polycarbamate. This method makes it possible to quantify 0.3
      microg/l of polycarbamate in tap water, which is a 1/100 of the residual target
      value of 30 microg/l in Japan. Moreover, it now becomes possible to distinguish
      polycarbamate from other dithiocarbamate pesticides (DTCs) that have similar
      structures, including ziram and thiram, which only incorporate a DMDC side chain,
      or manzeb, maneb and zineb, which only incorporate an EBDC side chain, by
      simultaneously analyzing for DMDC-methyl and EBDC-dimethyl.

PMID- 15941052
TI  - Integration of supercritical fluid chromatography into drug discovery as a
      routine support tool. Part I. fast chiral screening and purification.
AB  - Supercritical fluid chromatography (SFC) has been implemented within our group as
      a purity assessment and purification tool to complement high performance liquid
      chromatography (HPLC) for diastereomer and chiral separations. Using a novel
      strategy, rapid chiral screening has been implemented using short columns, high
      flow rates and fast gradients. A primary screen delivers a separation assessment
      using one solvent modifier (methanol) and four columns (Chiralpak AD-H and AS-H,
      and Chiralcel OD-H and OJ-H) run serially in a total of 24 min. A secondary
      screen then uses ethanol and isopropanol (IPA) modifiers across the same columns.
      The screens can be combined to run a sequence of samples overnight where each
      racemate is analysed over 80 min. The fast analytical screening and optimisation
      process enables rapid identification of the purification method. Furthermore,
      subsequent preparative chiral SFC has decreased the overall sample turnaround
      time for the Medicinal Chemist, delivering high fraction purities and acceptable
      recoveries, substantial operational cost savings and increased flexibility with
      respect to large scale purification feasibility in comparison to HPLC. SFC has
      been so successful it is now used as the primary method for chiral analysis and
      purification within our laboratory.

PMID- 15941053
TI  - Integration of supercritical fluid chromatography into drug discovery as a
      routine support tool. II. investigation and evaluation of supercritical fluid
      chromatography for achiral batch purification.
AB  - Supercritical fluid chromatography (SFC) has recently been implemented within our
      analytical technologies department as a purity assessment and purification tool
      to complement HPLC for isomer and chiral separations. This report extends the
      previous work to achiral analysis and purification. This internal evaluation
      explores the potential impact SFC can have on high throughput, batch
      purification. Achiral methods have been optimised and batches of compounds
      purified using a retention time mapping strategy. Here the preparative retention
      time is predicted from a standard calibration curve and fraction windows set to
      ensure the peak of interest is collected in one of the four available fraction
      positions. In this contribution, a completely indirect scale up strategy is
      applied using totally independent analytical and preparative methods. This novel
      approach allows for fast analytical purity analysis without compromising the
      ability to scale up to the preparative system. The benefits and limitations of
      SFC for batch purification are described in comparison to HPLC across a set of
      standard compounds and a set of 90 research compounds.

PMID- 15941054
TI  - Electrophoretic separation of aniline derivatives using fused silica capillaries
      coated with acid treated single-walled carbon nanotubes.
AB  - This paper reports on a new strategy for coating fused silica capillaries based
      on the ionic adsorption of acid treated single-walled carbon nanotubes (SWCNTs)
      on a poly(diallydimethylammonium chloride)-modified fused silica surface. The
      coated capillaries were used to demonstrate their performance for baseline
      separation of a mixture of seven nitrogen-containing aromatic compounds compared
      to capillary zone electrophoresis. This combined layer formed a coating material
      that could be useful for improvement of the selectivity of the solutes in an
      electrical field. We reasoned that the interaction of the solutes and the
      modified capillary wall occurred mainly via ionic interactions with the charged
      moieties of CNTs. The single-walled CNT modified capillaries were very stable and
      could be used for over 200 repeated analyses without compromising its analytical
      performance.

PMID- 15941055
TI  - Chiral separation of anticholinergic drug enantiomers in nonaqueous capillary
      electrophoresis.
AB  - Nonaqueous capillary electrophoretic (NACE) method for the separation of nine
      structurally similar chiral anticholinergic drugs was developed. The eight drug
      enantiomers were separated on baseline within 18 min using 20mM phosphoric acid
      and 10 mM NaOH, containing 10 mM heptakis(2,3-dimethyl-6-sulfato)-4beta
      cyclodextrin (HDMS-beta-CD) in methanol. The results were compared with those
      obtained in the high performance liquid chromatography system.

PMID- 15941056
TI  - Determination of antioxidants in cosmetics by micellar electrokinetic capillary
      chromatography with electrochemical detection.
AB  - A new and efficient method for the determination of antioxidants [Propyl gallate
      (PG), tert-butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA), and
      butylated hydroxytoluene (BHT)] in cosmetics has been established by using
      micellar electrokinetic capillary chromatography with electrochemical detection
      (MECC-ED). Under the optimum conditions of the method, all analytes were
      successfully separated within 13 min at the separation voltage of 18 kV in a 20
      mmol/L borate running buffer (pH 7.4) containing 25 mmol/L sodium dodecyl
      sulfate. The excellent linearity was obtained in the concentration range from 5.0
      x 10(-4) to 2.0 x 10(-6) mol/L and the detection limits (S/N = 3) of PG, TBHQ,
      BHA, and BHT range from 3 x 10(-7) to 3 x 10(-6) mol/L.

PMID- 15941057
TI  - Separation and determination of phospholipids in plant seeds by nonaqueous
      capillary electrophoresis.
AB  - A method has been developed for the separation and determination of phospholipids
      by nonaqueous capillary electrophoresis in a separation medium of acetonitrile-2
      proponol (3:2, v/v), 0.3% acetic acid and 60 mM ammonium acetate. To optimize the
      separation conditions, the composition of separation medium including alcohols,
      acetic acid, n-hexane and ammonium acetate was studied. The solvation interaction
      and ion-dipole interaction were also investigated. The contents of phospholipids
      in soybean, sunflower, peanut, apricot kernel, filbert and walnut were determined
      by the recommended method. The results obtained by the nonaqueous capillary
      electrophoreses were in good agreement with those determined by micellar
      electrokinetic chromatography.

PMID- 15941058
TI  - Direct olive oil authentication: detection of adulteration of olive oil with
      hazelnut oil by direct coupling of headspace and mass spectrometry, and
      multivariate regression techniques.
AB  - Control of adulteration of olive oil, together with authentication and
      contamination, is one of the main aspects in the quality control of olive oil.
      Adulteration with hazelnut oil is one of the most difficult to detect due to the
      similar composition of hazelnut and olive oils; both virgin olive oil and olive
      oil are subjected to that kind of adulteration. The main objective of this work
      was to develop an analytical method able to detect adulteration of virgin olive
      oils and olive oils with hazelnut oil by means of its analysis by a headspace
      autosampler directly coupled to a mass spectrometer used as detector
      (ChemSensor). As no chromatographic separation of the individual components of
      the samples exists, a global signal of the sample is obtained and employed for
      its characterization by means of chemometric techniques. Four different crude
      hazelnut oils from Turkey were employed for the development of the method.
      Multivariate regression techniques (partial least squares and principal
      components analysis) were applied to generate adequate regression models. Good
      values were obtained in both techniques for the parameters employed (standard
      errors of prediction (SEP) and prediction residual error sum of squares (PRESS))
      to evaluate its goodness. With the proposed method, minimum adulteration levels
      of 7 and 15% can be detected in refined and virgin olive oils, respectively. Once
      validated, the method was applied to the detection of such adulteration in
      commercial olive oil and virgin olive oil samples.

PMID- 15941059
TI  - Dioctadecyl L-glutamide-derived lipid-grafted silica as a novel organic
      stationary phase for RP-HPLC.
AB  - Dialkyl L-glutamide-derived lipids have been found to form supramolecular
      assemblies and to show specific properties based on their highly ordered
      structures in aqueous and organic media. To use these unique properties to create
      molecular recognition systems, dioctadecyl L-glutamide-derived lipid-grafted
      porous silica particles (Sil-DSG) were newly prepared and used as a stationary
      phase in reversed phase liquid chromatography. Compared with conventional ODS
      (octadecylated silica), the Sil-DSG column showed remarkably higher selectivity
      for polycyclic aromatic hydrocarbons (PAHs). Especially, Sil-DSG recognized the
      molecular linearity and planarity of PAHs. Suspension state 1H NMR and 13C CP/MAS
      NMR spectroscopies showed that the alkyl chains on the Sil-DSG are in gauche form
      and their mobility is strongly restricted at room temperature. This paper
      discusses higher selectivity of Sil-DSG with a carbonyl pi-benzene pi
      interactions.

PMID- 15941060
TI  - Determination of traces of chloride and fluoride in H2SO4, H3PO4 and H3BO3 by in
      situ analyte distillation-ion chromatography.
AB  - A simple dual vessel in situ analyte distillation (IAD) system has been developed
      for suppressed ion chromatographic determination of chloride and fluoride ions in
      complex matrices. In IAD system, water vapours generated from the outer vessel
      reacts with sulfuric acid generating heat, thus favouring the quantitative
      distillation of chloride and fluoride within 30 min on water bath temperature
      (approximately 80 degrees C). The distilled analytes, as their respective acids
      in water, were directly injected into an ion-chromatograph. This newly developed
      method has been applied for analysis of trace impurities in H2SO4, H3PO4 and
      H3BO3. The detection limits for chloride is 8, 80 and 70ppb (w/w) for H2SO4,
      H3PO4 and H3BO3, respectively. For fluoride the detection limits are 6 and 60 ppb
      (w/w) for H2SO4 and H3PO4, respectively. The recovery of spikes for both the
      analytes ranged between 87 and 100%.

PMID- 15941061
TI  - Essential oil composition of the different parts of Eryngium bourgatii Gouan from
      Spain.
AB  - The essential oil extracted from the different parts of Eryngium bourgatii Gouan:
      stems + leaves (E.b.SL), inflorescences (E.b.I) and roots (E.b.R), have been
      extracted by steam distillation and analysed by gas chromatography (GC) and gas
      chromatography coupled to mass spectrometry (GC-MS). Quantitative but not
      qualitative differences have been found between the analysed parts. The principal
      compounds from the inflorescences oil were found to be phyllocladene (37.6%) and
      bicyclogermacrene (15.1%), while the oil from stems and leaves showed
      phyllocladene (20.4%), gamma-muurolene (11.8%) and (E)-caryophyllene (10.1%) as
      main ones. The oil from the roots presented gamma-muurolene (15.4%) and
      phyllocladene (15.0%) as major constituents. It is worth mentioning the presence
      of a diterpene, phyllocladene, as main compound of the essential oil. This is the
      first report on the essential oil of this species.

PMID- 15941062
TI  - Human monoclonal IgMs with anti-Mycoplasma pneumoniae antibody activity.
AB  - We have previously reported that IgM antibodies to Pep13 P1, the major
      immunogenic peptide of Mycoplasma pneumoniae (MP) P1 cytoadhesin involved in
      microorganism cytoadherence, is a part of the natural antibody repertoire
      expressed early in life. Hence, Pep13P1 belongs to the panel of self and non-self
      antigens recognized by the primitive B cell repertoire. Considering that antibody
      activity of human monoclonal IgM associated with lymphoproliferative diseases is
      representative of the immune repertoire, we analyze, in this study, the antibody
      reactivity to P1 of twenty human monoclonal IgMs. Interestingly, we show that 25%
      of them are of anti-Pep13P1 specificity: one is a MIgM with reactivity against
      intermediate filaments, two are MIgMs with anti-MAG specificity and two IgMs with
      previously unknown antibody activity. Our results indicate that anti-P1 IgM
      antibodies are parts of the autoreactive than the heteroreactive B cell
      repertoire and Pep13P1 may have structural similarities with an unknown self
      antigen as the corresponding physiologic ligand.

PMID- 15941063
TI  - [Research on Parvovirus B19 infections and chronic articular manifestations in a
      Tunisian hospital].
AB  - Parvovirus B19 infection is often associated with acute and chronic joint
      diseases thus suggesting an etiologic role for the virus in these pathologies. In
      this work, we looked for a possible correlation between Parvovirus B19 infection
      and certain types of chronic inflammatory rheumatisms. We therefore, screened a
      population of 100 patients with different chronic inflammatory rheumatismal
      affections for serological markers of Parvovirus B19 infection. All patients were
      Tunisians of both sexes, who presented at the service of Rheumatology of the
      Charles Nicolle Hospital, Tunis. One hundred blood donors were taken as controls.
      Specific Immunoenzyme Assays of the ELISA type (Biotrin International, France)
      were used to detect anti-Parvovirus IgG and IgM. On the other hand, viral DNA was
      sought by nested PCR in synovial fluid from 14 patients. The data obtained
      indicate that specific anti-Parvovirus B19 IgG was detectable in the sera of
      80.7% of patients and 43% of controls. In contrast, none of the sera was found
      positive for specific IgM antibodies. Synovial fluid samples could be collected
      from 14 anti-Parvovirus B19 seropositive patients and were tested for the
      presence of viral DNA. None of the samples was found positive. The results of our
      serological study reinforce the hypothesis that Parvovirus B19 infection is
      associated with rheumatismal joint affections. However, the lack of detectable
      viral DNA in synovial fluid of the tested seropositive patients points to an
      indirect role of the virus in these joint disorders.

PMID- 15941064
TI  - [Risk factors of leishmanin-skin test positivity in transmission of Leishmania
      infantum in the center of Tunisia].
AB  - This work aims to estimate prevalence and evaluate risk factors of leishmanin
      skin test positivity. A cross-sectional leishmanin skin test study was carried
      out on a sample of 3190 healthy volunteers living in the gouvernorates of
      Kairouan and Kasserine. Age standardized prevalence of leishmanin-skin test
      positivity was 45.9% (CI95% = [43.9-47.9]) confirming the hyper endemicity of
      this region. The rate of leishmanin-skin test positivity ranged from 75.9% (CI95%
      = [71.9-79.5]) in Zaghdoud (Kairouan) to 6.5% (CI95% = [3.7-11.01) in Abdeladhim
      (Kasserine). There is no significant difference between men and women suggesting
      a similar exposure to infection. In the districts of Zaghdoud, Sidi Amor, El
      Hajeb and chbika, age specific rates showed a rapid increasing positive
      prevalence with age reaching a proportion exceeding 80% after the age of 15
      years. However, the age specific prevalence from other delegations showed a
      progressive increasing trend with age, with a low rate for younger children and a
      plateau of 75% after 45 years. Multivariate analysis of leishmanin-skin test
      positivity risk factors showed that only district and age are determinants of
      this infection.

PMID- 15941065
TI  - [Value of screening for intestinal and urinary parasites in non-resident
      permanent students in Tunisia].
AB  - In order to fight digestive and urinary parasitoses, a national program of
      surveillance has been founded. The screening of these parasitoses among the non
      permanent resident students in Tunisia (ENRPTS) is one of the main actions of
      this program. Among 2560 ENRPTS tested in the laboratory of Parasitologie of
      Institut Pasteur of Tunis, between 1998 and 2002, 674 were infected by parasites,
      which represents a global prevalence of 26.3%. The intestinal protozoa constitute
      the majority of parasites identified (87.4%). Entamoeba histolytica has been
      isolated in 89 cases, essentially from students from tropical African countries.
      Urinary bilharziosis has been diagnosed in 25 cases. These results confirm the
      utility of the control of the ENRPTS. The precocious tracking permits to avoid
      the introduction and the dissemination of parasites already absent or rare in our
      country.

PMID- 15941066
TI  - Molecular cloning and nucleotide sequence analysis of encoded anti-insect toxin
      BotIT2 from the scorpion Buthus occitanus tunetanus venom.
AB  - Numerous toxins from scorpion venoms are much more toxic to insects than to other
      animal classes, and possess high affinity to Na+ channels. Many of them active on
      insects were purified from the venom of Buthus occitanus tunetanus. Using amino
      acid sequences of BotIT2 and RACE-PCR amplification (Rapid amplification of cDNA
      ends) technique, we isolated, identified and sequenced the nucleotide sequence
      from the venom glands of the scorpion Buthus occitanus tunetanus. The cDNA
      encodes a precursor of an insect toxin of 60 amino acid residues. The deduced
      nucleotide sequence toxin was identical to the determined amino acid sequence of
      BotIT2. BotIT2 is more similar to the excitatory toxins in its mode of action and
      to the depressant toxins in its primary structure.

PMID- 15941067
TI  - [Characterisation of a novel toxin active on potassium apanaine channels,
      purified from Buthus occitanus tunetanus scorpion venom].
AB  - A new peptidyl inhibitor of the small-conductance Ca(2+)-activated K+ channels
      (SKca) was purified to homogeneity from the venom of the Tunisian scorpion Buthus
      occitanus tunetanus. The molecular mass determined by SDS-PAGE, shows that it's a
      short peptide (3300 Da). The primary sequence of this toxin shows that it is a 31
      residue polypeptide cross-linked by three disulfide bridges and structurally
      related to subfamily 5 of short scorpion toxins. This molecule shows similar
      pharmacological properties with this group of peptides inducing high toxicity in
      mice after intracerebro-ventricular injection, and competing with iodinated
      apamin for binding to its receptor site from rat brain synaptosomes (K0.5 = 4
      nM).

PMID- 15941068
TI  - [Importance of amastigote forms morphology to differentiate Leishmania infantum
      and Leishmania major species].
AB  - The microscopic study of the dermal smears of 62 cases of cutaneous leishmaniose,
      27 infected by Leishmania (L.) infantum and 35 by L. major, showed that the
      amastigotes of L. infantum are meaningfully smaller (p < 0.001). This criteria is
      a simple pary alternative to distinguish these 2 species which have completely
      different epidemiology, recovery delay and prophylactic dispositions.

PMID- 15941069
TI  - FNAB thyroid gland: comparison study between pre- and post-operative histological
      diagnosis.
AB  - Fine-needle aspiration biopsy is recommended as the first and most important step
      in the management of nodular thyroid disease. A retrospective study of 520
      patients with nodular thyroid disease was done in the north of Jordan, between
      January 1998 and August 2001. We compared the results of fine-needle aspiration
      biopsy (FNAB) of thyroid gland with postoperative histological findings. The
      results are classified into three groups A)-benign, B)-malignant, and C)
      suspicious as shown in table II. The results of the FNAB were benign in 96.4% of
      the cases which include benign colloid nodules (325 cases), multi-nodular goitre
      (70 cases), diffuse goitre (40 cases), thyroiditis (23 cases) and thyroid cysts
      (43 cases). A total of 52 patients underwent surgical management, 49 patients
      found to be accurate with the FNAB. The accuracy of FNAB was 94% (49 patients out
      of 52), with a specificity of 99% and a sensitivity of 93%. Ultrasound findings
      showed that 65% (338 patients) had solid nodules, 15% (78 patients) had cystic
      lesions and 20% (104 patients) had mixed echogenicity lesions. Histological
      confirmation of malignancy was 10 out of 11 patients with a 91% accuracy rate.
      FNAB was found to be a highly effective procedure, which can obviate a lot of
      unnecessary surgery in case of thyroid lesions, and avoid over treatment of
      benign disease. Surgery was recommended in all suspicious cases. FNAB under
      ultrasound guidance increases the sensitivity rate which can reach 100%. FNAB
      accuracy seems to be similar in cold and in hot nodules. Clinically, most of the
      patients with benign colloid nodules were having goitres suggesting the role
      played by iodine deficiency is which a prominent feature in that area in Jordan.

PMID- 15941070
TI  - [Tongue transplantation].

PMID- 15941071
TI  - Mast cells, masters, and mastocytosis: development of research since the times of
      Paul Ehrlich.

PMID- 15941072
TI  - The European Competence Network on Mastocytosis (ECNM).
AB  - The European Competence Network on Mastocytosis (ECNM) is a Europe-wide,
      multinational cooperative approach attempting to improve recognition, diagnosis,
      and therapy of mastocytosis. The network is composed of local centers,
      physicians, and scientists who have dedicated their work to patients with
      mastocytosis. However, because of the rarity and complexity of the disease, each
      single component in the network alone would fail to meet important demands and to
      reach solid conclusions in this field of applied medicine. The ECNM represents an
      attempt to overcome this restriction as a cooperative multicenter platform that
      should serve as an important basis for the development of new therapeutic
      strategies and diagnostic concepts, and for the standardization of techniques
      used to determine diagnostic and prognostic parameters. Moreover, using future
      central databases and registries, a suitable infrastructure for the development
      of co-operative multicenter clinical trials will be established. In addition, the
      ECNM is dedicated to provide the best available information about the disease to
      patients and physicians.

PMID- 15941073
TI  - [Immunization recommendations for travel in the Mediterranean area].
AB  - The Mediterranean region is a popular destination for tourists during the summer.
      However, European tourists, who are travelers within their own continent, do not
      consider themselves exposed to possible, travel-associated infections, since
      problem awareness among tourists as well as doctors is rather weak. The objective
      of this consensus paper is to outline guidelines with regard to relevant travel
      immunizations for Mediterranean destinations. These recommendations are mainly
      based on risk calculations according to country-specific incidences and
      prevalences of vaccine-preventable diseases such as hepatitis A, hepatitis B,
      typhoid fever, meningococcal meningitis, rabies, and tick-borne encephalitis.

PMID- 15941074
TI  - Gas voiding in an anuric patient.

PMID- 15941075
TI  - Estimation of seasonal variations in risk factor profiles and mortality from
      coronary heart disease.
AB  - OBJECTIVE: Seasonal variations in coronary heart disease (CHD) and related risk
      factors have been reported previously. However, no studies to date quantify the
      contribution of seasonal variations in risk factors to actual mortality in both
      men and women using a single database of sufficient size and follow-up. METHODS:
      We investigated the database from the Western Austrian Vorarlberg Health
      Monitoring and Promotion Programme (VHM&PP) including over 450,000 repeated
      measurements of 149,650 individuals between 1985 and 1999. RESULTS: Of a total of
      1266 deaths from CHD (ICD-9 410-414), 353 deaths occurred between December and
      February (27.9%), in contrast to 275 (21.7%) between June and August. While the
      frequency of deaths through acute myocardial infarction (ICD-9 410) was similar
      over the seasons, chronic forms of CHD (ICD-9 414) occurred significantly (p <
      0.001) more frequently in winter. Total cholesterol, blood pressure and body mass
      index showed pronounced seasonal variations with average levels significantly
      higher during the winter months in all age groups and both sexes, giving an
      estimated increase in score risk of 6.8% in men and 3.6% in women. However by
      contrast, use of single time point risk factor data tended to over-estimate
      subsequent 10 year mortality if measured in winter and the converse in summer.
      CONCLUSION: For the first time, this study quantifies the contribution of
      seasonal risk factor variation to CHD mortality. The consistent effect across
      demographic groups suggests that this is a real physiological phenomenon and not
      an artefact of living conditions. Interpretation of standard risk scores should
      take account of this seasonal fluctuation in subsequent investigation and follow
      up.

PMID- 15941076
TI  - Cancer mortality in Austria: 1970-2002.
AB  - PURPOSE: The aim of this study is to assess the overall progress against cancer
      in Austria by analyzing changes in age-adjusted mortality rates from 1970 to
      2002. METHODS: For the years 1970 through 2002, age-adjusted rates for all
      malignant neoplasms together and for selected cancers individually were
      calculated for men and women according to year and age. The data were obtained
      from Statistik Austria. RESULTS: Age-adjusted mortality rates of all cancers
      decreased in men by 22% and in women by 27%. The annual decrease of cancer
      mortality was 0.8% per year in the time period analyzed and 1.7% per year from
      1993 to 2002 in both sexes. Among older persons (> or = 55 years) the mortality
      decreased by 21% in men and by 25% in women; among younger persons (< or = 54
      years) by 25% and 40%, respectively. In individual cancer sites, the highest
      mortality rates are observed before the year 1995 in both sexes, except for liver
      and brain cancer in men (with the most recent peaks in the year 2001) and lung
      and brain cancer in women (with the most recent peaks in the year 2002).
      CONCLUSIONS: The observed changes in cancer mortality are primarily related to
      changes in incidence and, in the last decade, to improved treatment and early
      detection, but neither of these contributions can be quantified. The
      strengthening of prevention research (primary and secondary prevention) and
      further implementation of preventive knowledge is urgently needed.

PMID- 15941077
TI  - Morphology of erythrocytes of patients with ovarian cancer.
AB  - AIM OF THE STUDY: To investigate the morphology of erythrocytes in the peripheral
      blood of patients with ovarian cancer stage II and III. MATERIALS AND METHODS:
      The patient group consisted of 17 women (age 53 +/- 16 years) diagnosed with
      stage II or II ovarian cancer. The control group comprised 20 healthy women (age
      20 +/- 2 years). Seventeen samples of peripheral venous blood were collected from
      the cancer patients and 20 from the healthy women. These were then prepared for
      observation by scanning electron microscopy. RESULTS: The percentages of
      knizocytes and echinocytes were higher in the blood of patients than in that of
      the healthy controls. For knizocytes, the values for the mean +/- SD and the
      range were 2.45 +/- 3.72 and 0-15.7 vs. 0.66 +/- 0.57, 0.1-2.5, with p < 0.01.
      For echinocytes, these values were 1.94 +/- 1.04 and 0.5-3.6 vs. 1.03 +/- 0.71,
      0.1-2.6 and p < 0.01. Acanthocytes were present only in small numbers and were
      not evaluated. CONCLUSION: The proportion of erythrocytes with abnormal
      morphology in the blood of cancer patients before cancer therapy was
      significantly elevated as compared to that healthy controls.

PMID- 15941078
TI  - [Parental satisfaction with an outpatient asthma-management program for children
      and adolescents--a pilot study].
AB  - The objective of our asthma management program is to optimize the disease
      management and the quality of life of children and adolescents with asthma. An
      improvement in coping with asthma should be achieved by teaching theoretical
      aspects and practical skills. The training is performed in small groups of
      children and adolescents of similar age, going for 10 sessions each lasting 90
      minutes. Additionally, in 1999 and 2000, the program was also offered as a two
      week workshop in the summer holidays. The goal of this study was the assessment
      of parental satisfaction with the outpatient asthma management program for
      children and adolescents. We developed a short questionnaire and assessed the
      following aspects: general parental satisfaction with the training, judgement of
      the children's knowledge about asthma, coping skills and recommendation of the
      training. All parents (n = 138) whose children/adolescents attended the training
      between 1999 and 2002 were invited to take part in this study. 106 parents
      (76.8%) returned the questionnaire. The results showed that most parents (95%)
      were highly satisfied with this asthma management program. They equally
      positively rated their children's coping skills (87% classified them as "much
      better") and their knowledge (96% rated it as "very good" resp. "good") about
      asthma after the training. Almost all parents (97%) recommended our program. The
      results were very helpful for planning the recently started, prospective case
      control study on outcome evaluation of this program.

PMID- 15941079
TI  - [Patient anxiety and satisfaction in coloproctological operations].
AB  - BACKGROUND: Patients' emotional internal views related to coloproctological
      operations were examined, especially the relation between anxieties and
      satisfaction with treatment, including possible moderator variables such as age,
      gender, and control beliefs. PATIENTS AND METHODS: For 328 patients with
      operations on the rectum versus colon operations, intensity of anxiety, quality
      of anxiety, and their course was assessed. Likewise, satisfaction with medical
      care, subjective success of treatment, as well as control beliefs regarding
      illness and health were measured. The data were analyzed by means of analysis of
      (co-)variance, regression analysis, and discriminatory analysis. RESULTS: The
      emotional internal view turned out to have a greater influence than the objective
      severity of the operation. This also concerns specific, coloproctology-related
      contents of anxiety (e.g., anxieties concerning an anus praeter). For coping with
      anxiety, variables of a "talking medicine" are relevant. For this purpose,
      engaged communicative nursing care is important, though it cannot compensate for
      deficiencies in doctor-patient-communication. The latter must take into account
      the higher intensity of anxiety among younger patients as well as feelings of
      insecurity related to the hospital dismissal. CONCLUSION: These findings suggest
      the following improvements: the information provided by the physician should be
      more sophisticated, the clarification of diagnosis should take place as soon as
      possible, and the communication of the diagnosis should be combined with the
      reinforcement of internal control beliefs. This should apply to the transition to
      outpatient treatment as well.

PMID- 15941080
TI  - Premature rupture of membranes with oligo- or anhydramnios before 24 weeks of
      gestation and the chances of fetal survival.
AB  - Rupture of the membranes before the fetus has achieved viability within the womb
      is an event of enormous importance for both mother and physician. The potential
      outcome ranges from fetal death, a frequent occurrence, to a severely disabled
      life or a happy (but rare) birth without any mental or physical retardation for
      the child. The aim of the present investigation was to provide the consulting
      physician with valid data, enabling him/her to make a realistic assessment of the
      risks and to inform the patient accordingly. METHOD: In a retrospective analysis,
      we followed 36 cases with spontaneous rupture of the maternal membranes and
      development of oligo-/anhydramnios before 24 weeks of gestation. The patients had
      been treated between January 1994 and 2004. In a more detailed assessment, the
      patient cohort was divided into one group of women with rupture between 10 and 20
      weeks of gestation and another group with a gestational age between start of week
      21 and end of week 23. RESULTS: Of the 36 children, seven (19.4%) survived
      initially, with two of the seven survivors dying subsequently. Among women with
      amniorrhexis before week 21 of gestation, only three of the 26 children survived,
      while four of 10 children survived among women with premature rupture of
      membranes between 21 and 23 weeks of gestation (p = 0.053) No case of mental
      retardation could be observed in the surviving children. Perinatal outcome was
      found to be significantly different in the presence of amnionitis (3/27) compared
      to the group without this event (4/9) (p = 0.028). CONCLUSIONS: Because of the
      poor fetal outcome, termination of an ongoing pregnancy must also be considered
      in counseling the mother. If the mother decides to continue her pregnancy,
      amnionitis will be the most critical factor for ultimate termination of
      pregnancy.

PMID- 15941081
TI  - No adverse effect of ABVD chemotherapy in a patient with chronic hepatitis C and
      Hodgkin's disease.
AB  - There is insufficient information on the effects of chemotherapy protocols for
      Hodgkin's disease (HD) and the course of coexisting hepatitis C virus (HCV)
      infection. A single literature case reported a patient with HD who developed
      fulminant hepatitis and hepatic coma after receiving chemotherapy. The case
      described here is of a female patient previously exposed to prolonged war stress,
      complicated by intravenous drug abuse and chronic hepatitis C. One year after
      diagnosis of HCV infection she was diagnosed with HD (nodular sclerosis type II,
      clinical stage IIIB). The patient received six cycles of ABVD chemotherapy
      (doxorubicin, bleomycin, vinblastine and dacarbazine) resulting in complete
      remission of HD. There was no hepatitis flare either during or after
      chemotherapy. In conclusion, there were no adverse effects of the ABVD regimen on
      the course of HCV infection in this patient who was successfully treated for HD.
      Because concurrent HCV infection and HD is extremely rare, we discuss here the
      possibility of the synergistic contribution of chronic war stress and hepatitis C
      infection in the pathogenesis of HD.

PMID- 15941082
TI  - Kaposi's sarcoma-associated herpesvirus: clinical, diagnostic, and
      epidemiological aspects.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHI) is one of the few viruses proven
      to be associated with tumorigenesis in humans. Its causal association with all
      clinical and epidemiological variants of Kaposi's sarcoma (KS) is well
      established. KSHV is also involved in the pathogenesis of primary effusion
      lymphoma (PEL) and a subset of multicentric Castleman's disease (MCD). Possible
      associations of KSHV with other clinical settings have been extensively examined.
      The findings from several of these studies are contradictory and are yet to be
      resolved. Concentrated effort over the last decade, since the initial discovery
      of KSHV, led to the development of several experimental systems that resulted in
      a better comprehension of the biological characteristics of KSHV and set the
      stage for the understanding of mechainisms by which diseases are induced by the
      virus. The development of molecular, histological, and serological tools for KSHV
      diagnosis allowed researchers to track the transmission and to study the
      epidemiology of KSHV. These assays have been applied, in particular in ambiguous
      cases, in order to confirm clinically and pathologically based diagnoses. Here,
      we review the advances in the clinical, experimental, diagnostic, and
      epidemiological research of KSHV.

PMID- 15941083
TI  - Detection of disseminated tumor cells in peripheral blood.
AB  - Metastases are the major cause of cancer-related deaths in patients with solid
      epithelial malignancies, such as breast, colorectal and prostate carcinomas.
      Hematogenous spreading of tumor cells from a primary tumor can be considered as a
      crucial step in the metastasis cascade leading eventually to the formation of
      clinically manifest metastases. Consequently, as shown in recent studies, the
      detection of disseminated tumor cells in peripheral blood might be of clinical
      relevance with respect to individual patient prognosis and staging or monitoring
      of therapy. However, the rarity of disseminated tumor cells in peripheral blood
      renders the application of sensitive techniques mandatory for their detection.
      The emergence of highly sophisticated reverse transciptase-polymerase chain
      reaction (RT-PCR) assays, combining a preanalytical enrichment step with the
      assessment of multiple molecular tumor markers expressed in disseminated tumor
      cells, provides a powerful tool in detecting disseminated tumor cells with high
      sensitivity and specificity. This review will discuss currently used tumor
      markers as well as experimental means to enhance the sensitivity and specificity
      of RT-PCR assays to detect disseminated tumor cells in the peripheral blood of
      patients with breast, colorectal, and prostate cancers, and their clinical
      relevance assessed in recent studies.

PMID- 15941084
TI  - [The Botnar Center and clinical research].

PMID- 15941085
TI  - [Survival mechanisms to cellular stress].
AB  - Cells in our organism are constantly subjected to various types of stress that
      can lead to apoptosis, a form of programmed cell death. Apoptosis is induced when
      members of the caspase family of proteases are activated, either as a result of
      death receptor stimulation, or following cytochrome C release from the
      mitochondria. Cells can nevertheless survive in noxious conditions by activating
      a series of mechanisms that block or hamper caspase activation. As deregulation
      of apoptosis or of its regulatory check-points can lead to pathologies such as
      cancer and diabetes, a better understanding of apoptosis and its regulation is
      vital for the development of new therapeutical tools to treat these diseases.

PMID- 15941086
TI  - [Cerebral ischemia and apoptosis].
AB  - Ischemic stroke is an important cause of mortality and invalidity. Focal cerebral
      ischemia induces multiple and complex mechanisms leading to the loss of function
      and the demise of cerebral tissue. Apoptosis, or programmed cell death, well
      known for its role in normal development, is one of these mechanisms, and
      contributes to ischemic neuronal death. This short review gives an overview of
      apoptotic mechanisms triggered by cerebral ischemia.

PMID- 15941087
TI  - [Role of intracellular signalling pathways in the development of type 1
      diabetes].
AB  - Type I diabetes develops following an attack of the immune system that destroys
      the cells secreting insulin. Death of these cells however requires many
      intracellular mechanisms that are dependent of the insulin-secreting cells
      themselves. The pivotal role that the insulin-secreting cells play in their own
      destruction starts to be uncovered, and these new mechanisms are the target for a
      whole battery of future drugs.

PMID- 15941088
TI  - [Management of end-stage heart failure].
AB  - Non-medical approaches to end-stage heart failure (ESHF) include heart
      transplantation, but also implantable cardioverter-defibrillators, cardiac
      resynchronization therapy and ventricular assist devices. These techniques might
      be used as a bridge to transplant, as a bridge to recovery or as destination
      therapy. Optimal medical therapy of ESHF should include an angiotensin-converting
      enzyme inhibitor, a beta-blocker and spironolactone. Risk stratification in ESHF
      allows to determine the individual prognosis of each patient with parameters such
      as echocardiographic criteria, peak exercise oxygen consumption, or plasma BNP
      levels. Heart transplantation is to be considered if the individual prognosis
      obtained after stratification is worse than the expected survival of transplant
      recipients.

PMID- 15941089
TI  - [Use of intravenous immunoglobulin in neurological disorders].
AB  - The use of intravenous immunglobulin in the treatment of Guillain-Barre-Syndrome,
      chronic inflammatory demyelinating polyneuropathy and multifocal motor
      neuropathies is well established. Other conditions, such as dysglobulinemic
      neuropathy, myasthenia gravis, multiple sclerosis and inclusion body myositis may
      also benefit from the administration of intravenous immunoglobulins.

PMID- 15941090
TI  - [The patient and the financial incentives of physicians].

PMID- 15941091
TI  - [Thoughts on a year of functioning of the Tarmed].

PMID- 15941092
TI  - [Treating malaria for less than one dollar].

PMID- 15941093
TI  - [Should complementary medicine be reimbursed?].

PMID- 15941094
TI  - Exact and resampling probability values for weighted kappa.
AB  - Permutation procedures to compute exact and resampling probability values for
      weighted kappa are described. Comparisons with asymptotic probability values
      demonstrate that exact permutation procedures are advantageous for sparse data
      sets, whereas resampling permutation procedures are appropriate for both sparse
      and nonsparse data sets.

PMID- 15941095
TI  - Anchors distort estimates of expected duration.
AB  - This research explored the effect of presenting participants an anchor, which is
      a salient standard of comparison, before asking them to estimate the amount of
      time they believe they will need to complete a task (expected duration
      estimation). Such anchors can be assumed to be common in real-life situations,
      e.g., duration suggestions made by work colleagues. Participants were 32 students
      (M age = 23.1 yr., SD = 3.2; 28 women) who received course credit for
      participating. In the presence or absence of one of two anchors they had to
      estimate how much time they would need to work on a catalogue task. Actual time
      needed for the task was also measured. As predicted, analysis showed that
      estimates of expected duration were distorted in the direction of the anchors,
      i.e., estimations were assimilated into the presented anchor value. The
      implications for time management are discussed.

PMID- 15941096
TI  - Attitudes of university precalculus students toward mathematics.
AB  - To investigate the attitudes of 200 university students (83% freshmen) toward
      mathematics, a questionnaire was administered to report on their attitudes toward
      mathematics. Analysis indicated that students studying precalculus had a somewhat
      positive attitude toward mathematics.

PMID- 15941097
TI  - Personal information in searching for faces.
AB  - Participants searched for a target on a television monitor either after they
      viewed pictures and received physical information about the target or received
      that information augmented by personal information. Based on a levels of
      processing perspective we predicted that the addition of personal information
      would stimulate deeper processing and result in better identification
      performance. Personal information did increase identification accuracy, as
      anticipated. Personal information also increased the duration of time spent on
      the search task relative to a distractor task, suggesting that personal
      information may have done more than deepen the processing at the time of
      encoding. In the current climate of terrorism, this increase in identification
      performance via a surveillance camera has clear applied significance.

PMID- 15941098
TI  - Temporal stability of the Francis Scale of Attitude toward Christianity short
      form: test-retest data over one week.
AB  - This study evaluated the test-retest reliability of the Francis Scale of Attitude
      toward Christianity short-form. 39 Northern Irish undergraduate students
      completed the measure on two occasions separated by one week. Stability across
      the two administrations was high, r = .92, and there was no significant change
      between Time 1(M = 25.2, SD = 5.4) and Time 2 (M = 25.7, SD = 6.2). These data
      support the short-term test-retest reliability of the Francis Scale of Attitude
      toward Christianity short-form.

PMID- 15941099
TI  - Relation between school bullying during adolescence and subsequent long-term
      unemployment in adulthood in a Finnish sample.
AB  - The relationship between school bullying in adolescence and long-term
      unemployment in adulthood was investigated. A questionnaire was distributed to 68
      participants of a training program for people with long-term unemployment in
      Finland. Responses were compared with data of a nationwide investigation (sample
      53,394) of the prevalence of school bullying, according to which 8% of Finnish
      pupils are regularly bullied at least once a week. Among people with long-term
      unemployment, 29% reported having been exposed to school bullying at least once a
      week during their adolescence. This finding indicates a relationship between self
      reported school bullying in adolescence and long-term unemployment in adulthood.

PMID- 15941100
TI  - Nigerian undergraduate education majors' conceptions of mathematics.
AB  - The Conceptions of Mathematics Questionnaire by Crawford, et al. was administered
      to 130 southwest Nigerian undergraduate education majors who took mathematics.
      Coefficient alphas of .86 and .84 for the Fragmented and Cohesive subscales were
      similar to prior values. There were no statistically significant mean differences
      between men and women or between undergraduates taking mathematics with science
      and nonscience topics.

PMID- 15941101
TI  - Are over a third of foster parent molestations homosexual?
AB  - 50% of foster parent abuse in a general population survey and 34% of abuse as
      determined by the Illinois DCFS was homosexual. In news stories in the 50 largest
      newspapers and wire services 1980-2003, 175 foster parents sexually abused 351+
      charges. For the 169 whose sex of victim could be determined: 149 (88%) were men;
      76 (53%) victimized homosexually; and 85 (50%) were unmarried. Men assaulted 319
      (91%) victims, homosexual practitioners 222 (63%), and the unmarried 164 (47%).
      From 1980-1994 57% of the victims were girls; after 1994 56% were boys. In 21
      group homes, the molestation was homosexual in 15 (71%) and 31 of the 32+
      perpetrators were male and at least 334 of 349+ victims were boys.

PMID- 15941102
TI  - Relationship between two aspects of perfectionism and obsessive-compulsive
      symptoms.
AB  - In this study was investigated the relationship between two aspects of
      perfectionism (Concern over Mistakes and Personal Standards) and obsessive
      compulsive symptoms. College students (57 men and 193 women: M age = 19.5 yr., SD
      = 1.9) majoring in psychology were from introductory psychology classes and a
      psychological assessment practice class. They completed the Padua Inventory,
      which assesses obsessive-compulsive symptoms, and the subscales of Concern over
      Mistakes and Personal Standards of the Frost Multidimensional Perfectionism
      Scale, which assess the tendency to be concerned about making mistakes and the
      tendency to set excessively high standards, respectively. Multiple regression
      analysis indicated that only the Concern over Mistakes scores predicted
      significantly all Padua Inventory subscale scores. Perhaps only being concerned
      over making mistakes may be associated with obsessive-compulsive symptoms. The
      tendency to set high standards was not strongly correlated with obsessive
      compulsive symptoms. Further, the relationship between setting high standards and
      having obsessive-compulsive symptoms reported in previous studies may be
      spurious. Further work is required to untangle these associations.

PMID- 15941103
TI  - Sex differences on a measure of conformity: comments on a recent study.
AB  - Reysen and Reysen's recent article made a contribution to understanding of sex
      differences by interpreting the results through the lens of conformity research.
      Reinterpretation could refer to differences in perceptual sensitivity. The
      results, then, are theoretically and empirically consistent with the literature.

PMID- 15941104
TI  - An evaluation scale of family environment for identification of children at risk
      of school failure.
AB  - This study describes the development of the Home Environment Resources Scale, a
      Brazilian measure for families with children ages 6 to 12 years. The scale
      measures aspects of support for school achievement, made available to the child
      at home. A first version of the measure with 11 subscales was administered to 100
      mothers or guardians of children with poor school achievement in a clinical
      setting. Analysis of the items in the first version resulted in a final version
      comprising 8 subscales with acceptable indices of internal consistency. Two
      validity studies were conducted. One aimed at verifying to what extent the Home
      Environment Resources Scale could discriminate the home environment of students
      referred to a mental health clinic on account of poor school performance. The
      sample included mothers of 53 referred and 23 nonreferred children. The two
      groups differed significantly in home resources and on four subscales. The other
      study assessed the validity, i.e., prediction of the academic outcome of children
      entering Grade 1. 70 children and their mothers participated. Results indicate
      that school achievement and social competence at school are mediated by family
      support.

PMID- 15941105
TI  - Comment on Soar, et al.'s case study of problems and use of Ecstasy.
AB  - This case report provides no basis for drawing any conclusions regarding possible
      adverse effects of use of Ecstasy.

PMID- 15941106
TI  - Values of fathers for themselves and their newborns.
AB  - The paternal role has been neglected in parenting research. The present study
      focused on the values of fathers of newborns. Values of fathers of newborns drawn
      from the inner-city lower-class were compared with values of fathers of newborns
      drawn from the middle class. Highest goals of fathers from both groups for
      themselves were economic ('family security'); values for their children were
      morally focused ('honest'). Inner-city fathers placed a higher value on a clean
      and obedient child, whereas middle-class fathers placed a higher value on a
      loving and imaginative child. When values of these fathers were compared with
      values of a similar sample of mothers of newborns, socioeconomic status remained
      an important predictor of values. Sex of parent was significant in the inner-city
      sample as these fathers placed a higher valuation on goals associated with
      autonomy than did inner-city mothers.

PMID- 15941107
TI  - Reply to Schumm's argument that ending the gay ban will morally "injure" some
      service members.
AB  - Schumm does not explain why moral injuries that would ensue from serving
      alongside peers who utter the words "I am gay" warrant protection in federal law.

PMID- 15941108
TI  - Low income, unemployment, and suicide mortality rates for middle-age persons in
      Japan.
AB  - The relationships between age-specific suicide mortality rates and social life
      factors for all 47 Japanese prefectures in 1980, 1985, and 1990 were assessed by
      multiple regression analysis after factor analysis on 20 social life indicators.
      During this period, Japan experienced a secondary oil crisis in 1980-1983 and a
      bubble economy in 1986-1990. It was concluded that (1) low income was the major
      determinant which positively affected suicide mortality rate in middle-aged men
      during a previous 20-yr. period (1970-1990), (2) urbanization was negatively
      associated with male suicide mortality rates in most of the age classes in the
      1980s, (3) unemployment was one of the major determinants of increased suicide
      mortality rate in middle-age men in the 1980s, and (4) unemployment was the major
      factor which was inversely associated with suicide mortality rate for elderly
      women from 1980 to 1990 in Japan.

PMID- 15941109
TI  - Context in selection of men and women in hiring decisions: gender composition of
      the applicant pool.
AB  - The hypothesis that the sex composition of an applicant pool affects the hiring
      probabilities of individual job applicants was tested using gender-distinctive
      information on accepted and rejected job applicants in The Netherlands. The
      evidence supports this hypothesis, although the effect sizes are moderate. Both
      men and women have a lower probability of being hired when the applicant pool
      contains fewer applicants from their own sex.

PMID- 15941110
TI  - Relations between female students' personality traits and reported handicaps to
      rhythmic gymnastics performance.
AB  - The present study evaluated the relative contributions of Self-esteem, Trait
      anxiety, and Public Self-consciousness to self-handicapping on a sex-typed task,
      within a specific academic sport context. Prior to the competitive examination
      used to recruit French Physical Education Teachers, female sport students (N =
      74) were asked to list and rate on a 7-point scale handicaps which could be
      disruptive to their Rhythmic Gymnastics performance. Self-esteem did not account
      for significant variance in any category of handicaps. Trait Anxiety was
      negatively related to handicaps related to Rhythmic Gymnastics and to Social and
      Work Commitments. Public Self-consciousness was significantly related to
      endorsement of Friends and Family Commitments handicaps. These results were
      discussed in relation to the literature.

PMID- 15941111
TI  - Following instructions on a final examination: an informal look.
AB  - Of a total of 914 undergraduate college students over 5 years 600 (about 66%)
      were in full compliance with a simple instruction for how to enter their names on
      their final examination papers; approximately 33% were not. The compliance rate
      over the years declined from 73% to 59%.

PMID- 15941112
TI  - Comparing market orientation culture of businesses and schools of business: an
      extension and refinement.
AB  - This study extends previous work concerning the market orientation culture within
      specialty businesses and schools of business. Specifically, member schools of the
      Association to Advance Collegiate Schools of Business International are separated
      into public and private universities. Data were collected via a mailed survey to
      business schools holding membership. 106 public school deans and 35 private
      school deans responded, for a 23% response rate. Input from the deans was sought
      on their perceptions of the market orientation culture within the schools.
      Respondents' perceptions, rated on a 7-point scale, measured four dimensions of
      market orientation: customer orientation, competitor orientation, organizational
      coordination, and overall market orientation. Data for specialty businesses were
      drawn from a previous study. Comparison testing between the public and private
      business schools' deans and business managers was conducted. Analysis indicated
      perceived market orientation was significantly higher for deans of private
      business schools than public business schools. Compared with business managers,
      private school deans were statistically different on only one of the four
      dimensions, whereas public business school deans' scores were significantly
      different from those of business managers on all four. Compared with each other,
      business school deans were statistically different on three dimensions, with
      private school deans reporting greater market orientation.

PMID- 15941113
TI  - Strengths and distress in adults who are aging with HIV: a pilot study.
AB  - In this qualitative pilot study, distress and strengths associated with aging
      with Human Immunodeficiency Virus (HIV) were identified for 12 participants.
      Potential sources of distress were fear of death, financial worries, fear of
      disclosure, stigma, and long-term coping. Strengths were hardiness, renewed
      spirituality, social support, community service, and openness to aging. Ways of
      mitigating these barriers and accentuating these strengths can be explored by
      mental health professionals if extended with a representative larger sample.

PMID- 15941114
TI  - Does self-consciousness mediate the relation between self-talk and self
      knowledge?
AB  - Building on Morin's understanding of the relations among self-talk, self
      consciousness, and self-knowledge, this study examined the hypothesis that
      functional and dysfunctional self-consciousness mediate between self-talk and
      self-knowledge. A self-report questionnaire including 10 scales assessing
      different aspects of Self-talk, Self-consciousness, and Self-knowledge was
      administered to 200 German undergraduate university students (95 women, 105 men).
      Mediation analysis showed that the observed negative relationship between Self
      talk and Self-knowledge was mediated by Dysfunctional Self-consciousness, while
      Functional Self-consciousness acted like a supressor variable. The discussion
      focuses on limitations of the present measures of Self-talk.

PMID- 15941115
TI  - Oddities in Kirkpatrick, et al.'s study of children of lesbian mothers.
AB  - Kirkpatrick, et al.'s 1976 study of what happened to 20 lesbians' children has
      received considerable attention, apparently later being matched with 20
      heterosexuals' children. In 2004, Kirkpatrick generally acknowledged Schumm's
      caution that her findings are less impressive than are needed, yet, Kirkpatrick
      stated her "early findings have been reinforced" and that "no evidence of
      differences in the children grouped by the mother's sexual orientation" have been
      documented by subsequent research. Close examination of the data of these studies
      indicates that children from 13 lesbian mothers were compared with children from
      13 divorced heterosexuals. Further, there are contradictions between the
      published reports regarding the nature of samples and various findings. Analysis
      of Kirkpatrick, et al.'s study suggests that children do less well when raised by
      homosexual parents.

PMID- 15941116
TI  - Revisiting the factor structure of the Kirton Adaption-Innovation Inventory.
AB  - The original Kirton Adaption-Innovation Inventory, used to measure innovative (as
      opposed to adaptive) individual cognitive styles, has been reported to have three
      factors: Sufficiency of Originality, Efficiency, and Rule/Group Conformity. In
      exploring the construct validity of the Kirton Adaption-Innovation Inventory,
      findings from a 2003 study by Im, Hu, and Toh showed the existence of two
      subdimensions of the Sufficiency of Originality factor-Idea Generation and
      Preference for Change. In this study, using a sample of 356 household
      participants, with an average age of 56.0 yr. (SD = 14.0), average income of
      dollar 39,700 (SD = dollar 19,200), and average of 15.0 yr. of education (SD =
      2), from the Arkansas Household Research Panel, we conducted factor analyses. The
      results specific to our selected sample indicate that a four-factor model
      recognizing the two subdimensions of Sufficiency of Originality has a better fit
      than the original three-factor model.

PMID- 15941117
TI  - Use of a religious hymn in remission of symptoms of social phobia (social anxiety
      disorder): a case study.
AB  - This case report described a veteran with social anxiety disorder who reported
      fears of negative evaluation by others, social avoidance, and accompanying
      physiological symptoms of heart palpitations, gastrointestinal discomfort, muscle
      tension and mental confusion. The symptoms of social anxiety disorder subsided
      with the use of a Christian hymn "Be Still My Soul" and its accompanying musical
      poem, in Finlandia. The veteran attributed the symptom remission to the feeling
      of stillness and surrender to God conveyed by the words and music of the hymn.
      Although previous studies have shown that both music and religious beliefs can
      affect mental health, the findings in this case cannot be generalized without
      conducting further prospective empirical studies.

PMID- 15941118
TI  - Differences in mathematics anxiety by sex, program, and education of university
      mathematics students in Turkey.
AB  - In this study, we aimed to re-examine sex-related differences in mathematics
      anxiety and to investigate the effects of two different programs associated with
      mathematics education applied in Turkish universities on mathematics anxiety.
      Mathematics anxiety scores were assessed in 221 male and 142 female students, 238
      in the education faculty and 125 in the science faculty. There were no sex
      related mean differences for mathematics anxiety scores, and scores were not
      related to faculty program. The lower mean mathematics performance on the
      university entry examination of the students of science faculty may be associated
      with the mathematics anxiety.

PMID- 15941119
TI  - Cross-modality priming for people's adjectivized names: failure to support the
      adjectivization hypothesis.
AB  - This experiment tested a prediction derived from Hollis and Valentine's 2001
      adjectivization hypothesis, that having an adjectival form is the key factor that
      makes certain classes of proper names, i.e., country names, exhibit a common name
      like pattern of long-term priming. The hypothesis predicted that, when
      adjectivized historical celebrity names, e.g., William Shakespeare/Shakespearean,
      were compared with nonadjectivized historical celebrity names, e.g., Emile Zola,
      cross-modality long-term priming in a familiarity decision task would occur only
      for nonadjectivized name stimuli. 32 students of literature, history, or
      philosophy (21 women and 11 men; age range 18-41 years, M age = 22.4 yr.) were
      tested. Priming was measured by latency of response. Analysis showed that the
      mean RT to primed items was faster than the mean RT to unprimed items when the
      prime task was presented in both visual and auditory modalities both for the
      adjectivized and nonadjectivized names. Contrary to the hypothesis, cross
      modality priming was observed regardless of the adjectivization of name stimuli.
      The findings of the present experiment did not support the adjectivization
      hypothesis.

PMID- 15941120
TI  - Sleep disturbances associated with age and HIV.
AB  - Sleep disturbances are common in normal people of several age groups and those
      with Human Immunodeficiency Virus (HIV) disease. In a secondary analysis of data,
      50 HIV-positive and 50 HIV-negative adults between 30 and 65 years old responded
      to 5 items about sleep. No statistically significant differences by HIV status or
      age group were found.

PMID- 15941121
TI  - Anxiety and depression in adolescents in urban and rural China.
AB  - The goal was to assess rates of anxiety and depression in adolescents in two
      areas of Zhejiang Province, China. A cross-sectional survey was carried-out using
      a self-report questionnaire developed for this study. Participants were middle
      school students (age range 13-16 years) in an urban and a rural setting. There
      were 1576 completed questionnaires. Symptoms of anxiety sufficient to interfere
      with enjoyment of life, relaxation, and sleep were common (48%, 40%, and 27%,
      respectively). School-related problems were the predominant sources of worry. One
      third reported a history of depression, 16% had at times felt life was not worth
      living, and 9% reported that they had attempted suicide. Girls were more likely
      to report symptoms of depression. Patterns of help-seeking showed reliance on
      friends and parents; only 1% had sought professional help. There were no
      significant differences in anxiety and depression between one-child and
      multisibling families.

PMID- 15941122
TI  - Discriminating among diagnostic categories using the Dissociative Disorders
      Interview Schedule.
AB  - The Dissociative Disorders Interview Schedule was administered to 1,308 subjects
      in eight diagnostic categories, including 296 with dissociative identity
      disorder. The study tested three hypotheses: (1) the Mahalanobis distance between
      dissociative identity disorder and each of seven other diagnostic categories
      would be large, (2) the closest diagnostic category to dissociative identity
      disorder would be dissociative disorder not otherwise specified, and (3)
      nondissociative diagnostic categories would be closer to each other than any one
      to dissociative identity disorder. All three hypotheses were confirmed by these
      data. The findings support the conclusion that dissociative identity disorder is
      a discrete category or taxon.

PMID- 15941123
TI  - Lee Acculturation Dream Scale for Korean-American college students.
AB  - This study examined acculturation as represented in dream narratives of 165
      Korean immigrant college students living in the USA. A total of 165 dreams were
      collected and evaluated using the Lee Acculturation Dream Scale, for which
      locations of dream contents were coded. 39% of the dreams took place in South
      Korea, while 38% were in the USA. Also, 16% of the dreams included both
      locations, whereas 7% had no specific dream location. The dreams contained
      overlapping dream messages, images, scenes, and interactions in both South Korea
      and the USA. A two-sample t test on the mean scores of the Lee Acculturation
      Dream Scale indicated no significant difference between men and women.

PMID- 15941124
TI  - Perceived gender of a pastor's name and ratings of vocational success.
AB  - Undergraduate students (16 men and 16 women) from a Christian university read a 1
      page description of a pastor named either "Carl Anderson" or "Carol Anderson."
      Students rated each named pastor on four items summed for a measure of vocational
      success. We predicted, based on role congruity, that students would rate a female
      named pastor lower than a male-named pastor on the measure, but women's ratings
      of pastoral vocational success were significantly higher. Men's ratings did not
      differ significantly for the male- and female-named pastors. Power was low so
      further research is appropriate.

PMID- 15941125
TI  - The Motivation Analysis Test: an historical and contemporary evaluation.
AB  - This is an historical review and contemporary empirical evaluation of the
      Motivation Analysis Test (MAT), one of the first tests to take a psychometric
      approach to the assessment of motivation. Reviews were quite positive, but the
      test is now over 50 years old. Nevertheless, it employs innovations in
      measurement not widely used in objective measurement then or now: (1) subtests
      with different formats, (2) disguised items, (3) speeded administration
      procedures, and (4) ipsative format and scoring procedures. These issues are
      discussed and a contemporary sample (N = 360) obtained to evaluate the Motivation
      Analysis Test in light of its innovative characteristics.

PMID- 15941126
TI  - Verbal aggressiveness of physical education teachers and students' self-reports
      of behavior.
AB  - The purpose of this study was to develop a test for describing verbally
      aggressive behaviors of physical education teachers as perceived by secondary
      school students. The sample of 130 students (70 boys and 60 girls) were students
      in the second year of secondary school in Greece. 12 items designed for students
      were structured to describe possible verbal aggressive behaviors of physical
      education teachers as perceived by students and students' intention to respond.
      Exploratory factor analysis using the principal components method and varimax
      rotation yielded three factors, namely, (i) personal insults, threats, irony and
      their effect, (ii) intention to respond, and (iii) insults and threats toward
      others. Eigenvalues were greater than 1.00 for each of three factors which
      accounted for 69% of the total variance. Values of Cronbach alpha were .86, .88,
      and .78 for the three factors, respectively.

PMID- 15941127
TI  - Influence of sex differences in leaders' behavior.
AB  - Sex differences in influence tactics were examined with a sample of 269 followers
      (67 men, 202 women) at a large midwestern national insurance company who rated
      the downward influence tactics used by their direct supervisors. Downward
      influence tactics are behaviors used by leaders to gain compliance from
      followers. One department within the organization was identified as a source for
      participants in the study. Participation was voluntary. The age range for the
      sample was 21 to 65 years, with the largest percentage falling in the 40-49 year
      range (M = 3.8, SD = .8). Hierarchical linear modeling procedures were utilized
      to analyze the multiple level data (leader and follower) and to examine variables
      within the organization at different levels of analysis. Leader participants were
      asked to solicit their followers to complete an influence tactic measure, which
      consisted of the most reliable subscales taken from the Influence Behavior
      Questionnaire, Schriesheim and Hinkin Influence Measure, and the Profiles of
      Organizational Influence Strategies. The integrated measure resulted in a 45-item
      scale. It was hypothesized that, overall, followers would report that male
      leaders would use hard influence tactics more frequently than female leaders. On
      the other hand, followers would report that female leaders would use soft
      influence tactics more frequently than male leaders. When differentiating
      followers by sex, however, we expected that male followers would report more than
      female followers that their leaders use hard tactics more frequently. Also, we
      expected that female followers would report (more than male followers) that their
      leaders use soft tactics more frequently. Overall, followers reported that male
      leaders used significantly more personal appeal and consultation, so called "soft
      tactics," with their followers than did female leaders. Female followers reported
      that their leaders (both male and female) used consultation and inspirational
      appeal more frequently. In contrast, male followers reported that their leaders
      used exchange, so called "hard tactics," more frequently.

PMID- 15941128
TI  - Accuracy of self-reports of alcohol offenders in a rural midwestern county.
AB  - Self-reports of drinking are of doubtful accuracy as heavy drinkers tend to
      underreport consistently amounts drunk as well as other alcohol-related data. A
      sample of 60 people cited for DWI in a rural midwestern county in southeast
      Nebraska during routine alcohol-dependency evaluations indicated that 10%
      underreported their Breath Alcohol Content at the time of arrest and 38% their
      previous number of DWI citations. Subjects were grouped by age (over and under
      30) and by accuracy (accurate and inaccurate reporters). A 2 x 2 analysis of
      variance of later DWI arrests was significant as younger subjects showed greater
      risk. Those who underreported number of past DWI citations were significantly
      lower on their self-reported BAC at the time of arrest than accurate reporters.
      Age and underreporting alcohol-related data are as important for practitioners to
      attend to as scores on the Michigan Alcoholism Screening Test or SCID measuring
      alcoholic tendencies.

PMID- 15941129
TI  - Parenting and marital trust in Japan.
AB  - This study examined the relationship between marital trust, mothers' parenting
      stress and maladjusted parenting behavior in Japan. The participants consisted of
      327 Japanese mothers who reside in the greater Tokyo area and whose children go
      to kindergarten or nursery school (the children's ages range from 3 to 6 years.
      Participants were asked to complete questionnaires about their family structure
      (nuclear or extended family), demographic information about their child (sex,
      age, birth order. etc.), marital trust, parenting stress, and maladjusted
      childrearing behavior. Analysis indicated that the relationship between marital
      trust, mothers' parenting stress and maladjusted childrearing behavior was
      different depending on the family structure. More specifically, for mothers in
      nuclear families, marital trust, especially the sense of being trusted by the
      husband, was associated with parenting behavior directly as well as indirectly
      via parenting stress. In contrast, for mothers in an extended family marital
      trust was not associated with maternal parenting behavior. The results were
      discussed in terms of the differences in the availability of social support in a
      nuclear family compared to the extended family.

PMID- 15941130
TI  - Pilot assessment of pain of orthopaedic patients in Hong Kong.
AB  - This pilot study examined the internal consistency and concurrent validity of the
      Chinese version of the Acute Lower Back Pain Screening Questionnaire. A sample of
      45 acute low back pain patients (27 men and 18 women; mean age = 47.8) were
      recruited from the Department of Orthopaedics and Traumatology of the Tuen Mun
      Hospital in Hong Kong. Three items of the original questionnaire were excluded
      from the analyses because response was low by 30 of the 45 patients. The
      questionnaire showed good internal reliability (Cronbach alpha = .88) and
      correlated significantly with other test scores: the Faces Pain Scale-Revised
      (alpha = .74), the Chinese (Hong Kong) SF-12 Health Survey (Mental subscale,
      alpha = -.47; Physical subscale alpha = -.62), and the Chinese Hospital Anxiety
      and Depression Scale (Anxiety subscale, alpha = .42; Depression subscale, alpha =
      .43). The questionnaire could be used in research and clinical work to provide
      data on the multicomponents of a pain experience as well as psychosocial risk
      factors related to pain among the Chinese. Researchers might examine the course
      of change in chronic pain.

PMID- 15941131
TI  - Why do people reject unintended inequity? Responders' rejection in a truncated
      ultimatum game.
AB  - Rejection of an inequitable and yet unintended outcome in a truncated ultimatum
      game was examined in an experiment with 46 undergraduate students (27 men and 19
      women) from a large national university in Japan. In an ultimatum game, one of
      two players, the proposer, makes an offer to divide a fixed-sum of money. The
      other player, the responder, decides whether to accept or reject the offer. When
      the responder rejects the proposer's offer, neither of the two players receives a
      reward. Previous work examining the behavior of participants in the truncated
      ultimatum game employed strategy method in their experimental design. We examined
      whether these previous findings would be replicated in an experimental design
      that did not use the strategy method and instead used the standard one-shot game.
      Seven out of 46 responders given an inequitable offer rejected it, replicating
      prior results with the strategy method. We further found that subjects who
      rejected an offer that was involuntary and yet inequitable did not over-attribute
      intentions to the proposer's involuntary behavior more strongly than did
      acceptors. These findings strongly suggest that aversion to inequity is the
      explanation for the subjects' rejection of the inequitable offer.

PMID- 15941132
TI  - Wealth is associated with lower anxiety in a sample of Lebanese students.
AB  - A sample of 160 Lebanese students in the American University at Beirut (a
      relatively wealthy sample) had a significantly lower mean score on the Kuwait
      University Anxiety Scale than a sample of 639 Lebanese students in the Lebanese
      University (a less wealthy sample). Sex differences in anxiety scores were not
      significant in the first sample, but were in the second.

PMID- 15941133
TI  - Interpretation of MMPI-A Scale 5 with female patients.
AB  - The present report describes clinical data useful in interpreting the meaning of
      elevations of Scale 5 of the MMPI-A with adolescent girls. Previous commentaries
      on the clinical significance of such scores have been ambiguous. The present
      findings suggest that scores which are elevated but still below a T value of 65
      on this scale will be associated with acting out in treatment settings.

PMID- 15941134
TI  - [Extracorporal methods in transfusiology].

PMID- 15941135
TI  - [Nephrological aspects of obesity].

PMID- 15941136
TI  - [Intestinal dysbiosis (dysbacteriosis) and/or "excessive bacterial growth
      syndrome"].

PMID- 15941137
TI  - [Influence of therapy with atenolol on lethality of patients with chronic heart
      failure].
AB  - The paper demonstrates that the hydrophilic beta-adrenoblocker (BAB) atenolol is
      effective in patients with III-IV functional class chronic heart failure (CHF),
      associated with postinfarction cardiosclerosis (PIC) and dilatational
      cardiomyopathy (DC). In reduction of general and cardiovascular mortality in the
      given category of patients atenolol was not less effective than the lipophilic
      BAB bisoprolol (in comparison with the results of the CIBIS II study). Sudden
      death was typical of the patients with DC, whereas most of PC patients died of
      repeated myocardial infarctions and progressive CHF. There was no significant
      difference between lethality in DC and PIC groups (p > 0.05). The results of the
      study suggest that hydrophilic BABs are not less effective in improving the
      prognosis than lipophilic BABs. Further research into this problem is
      appropriate.

PMID- 15941138
TI  - ["Function-corrected" indexes for precise estimation of aortic stenosis
      severety].
AB  - The aim of the research was to study clinical significance of "function
      corrected" indexes (FCI) in non-invasive evaluation of aortic valvular stenosis
      (AVS) severity. 85 patients with degenerative aortic valve calcification (42 -
      with AVS and 43 - without aortic ostium (AO) stenosis) were subjects of a cross
      sectional study. Significant correlation between AO area and FCI indexes was
      demonstrated. When it is not possible to determine AO by planimetric methods, it
      may be counted using FCI with good sensitivity (87%) and specificity (94%).

PMID- 15941139
TI  - [Enterosorption in complex therapy of bronchial asthma].
AB  - Generation of active oxygen forms in whole blood was studied in 84 patients with
      bronchial asthma (BA) by luminol-enhanced chemiluminescence (Chl) registration.
      Chl intensity depended on inflammatory process expression; groups of patients
      with high and low blood Chl (the 1st and the 2nd group, respectively) were
      distinguished. Enterosorption was used in complex therapy of 8 patients of the
      1st group and 15 patients of the 2nd group. Indices of free radical oxidation and
      content of average molecular oligopeptides in blood serum normalized in the
      patients who took enterosorbent; the remission in these cases was more complete.
      The results of the study suggest that enterosorption increases effectiveness of
      treatment in patients with BA.

PMID- 15941140
TI  - [Genotypic and phenotypic markers in patients with chronic obstructive
      bronchitis].
AB  - The study included examination of 120 patients with chronic obstructive
      bronchitis (COB) and 70 healthy people. The following genotypic and phenotypic
      markers were evaluated: blood group, Rhesus factor, earwax type, constitution,
      height, iris color, hair color, signs of functional asymmetry and some minimal
      signs of embryogenesis disturbances. The relative risk of the disease development
      was counted for each parameter. The study found the highest COB morbidity in
      short normosthenics people with short neck, wet earwax type, nasal septum
      deviation and B (III) blood group. Such markers as light brown hair and dry
      earwax type were shown to be associated with COB-protective activity. The signs
      discussed in the article may be used to determine predisposition to COB.

PMID- 15941141
TI  - [Clinical and morphological features of alcoholic steatohepatitis].
AB  - 48 patients with alcoholic steatohepatitis (ASH) were examined and divided into 3
      groups according to the degree of fatty liver infiltration. It was minimal in 8
      (16. 6%) patients, moderate in 10 (20.8%) and severe in 30 (62.5%) patients. The
      higher the degree of the fatty infiltration, the more pronounced dystrophic
      alterations and the more often necrosis, fibrosis and cell infiltration focuses
      were found in liver biopsy material. Morphologic changes in biopsy samples from
      ASH patients were much more pronounced in comparison with those in non-alcoholic
      steatohepatitis (NASH). The latter is characterized mostly by lymphocyte
      infiltration, while leukocyte infiltration is more typical of ASH. The study
      found prominent alterations in serum lipoprotein spectrum, triglyceride (TG) and
      saturated fatty acid concentrations in patients with ASH. High concentrations of
      chylomicrons, low-density lipoproteins and TG were registered together with low
      levels of high-density lipoproteins and albumin complex.

PMID- 15941142
TI  - [Clinical and biochemical characteristics of biliferous tract diseases in
      patients with diabetes mellitus].
AB  - The aim of the study was to investigate manifestations of biliferous tract
      diseases in patients with diabetes mellitus (DM) and to measure concentrations
      and the ratio of lipids in gall-bladder and liver bile in these patients.
      125patients with DM and biliferous tract diseases were examined. Patients with
      chronic cholecystitis (CC), cholelithiasis, and biliary dyskinesia underwent
      clinical examination as well as biochemical and instrumental tests. The control
      group included 87 healthy individuals of comparable age and gender. CC was
      diagnosed in 35.2% of DM patients, cholelithiasis - in 17.6% patients. In liver
      and gall-bladder bile samples taken from patients with CC and cholelithiasis,
      fatty acids concentrations was not significantly different, cholesterol level was
      significantly higher, and phospholipids level was lower than in the control
      group. Thus, indices of cholesterol saturation in liver and gall-bladder bile
      portions were higher in patients with cholelithiasis than in the control group.
      The study revealed high biliferous tract diseases morbidity in patients with DM.
      Thomas-Hofmann index, which characterizes bile saturation with cholesterol, is
      significantly higher in patients with cholelithiasis and DM, then in healthy
      individuals.

PMID- 15941143
TI  - [Peculiarities of ulcerous and erosive lesions of gastroduodenal zone in patients
      with arterial hypertension].
AB  - The aim of the research was to evaluate peculiarities of ulcerous and erosive
      lesions of gastroduodenal zone (UELGDZ) in patients with arterial hypertension
      (AH). The authors studied clinical and endoscopic parameters in 442 patients with
      UELGDZ and AH, and 160 patients without AH (control group). The feature of the AH
      group was more frequent HP-invasion, aggravation of ulcerous process, development
      of complicated and atypical forms of the disease. In the patients with AH the
      clinical manifestations of chronic erosive gastritis were more diverse and
      severe; unfavorable clinical course prevailed. Risk of cardiovascular
      complications varied from low to very high, correlating with the severety of AH
      and UELGDZ.

PMID- 15941144
TI  - [Clinical effectiveness of dehelmintization in patients with psoriasis
      accompanied by chronic opisthorchosis].
AB  - The purpose of the study was to prove the appropriateness of dehelmintization in
      patients with psoriasis accompanied by chronic opisthorchosis (CO). The authors
      examined 150 patients with psoriasis accompanied by CO, 100 patients having
      psoriasis without helminthiasis, 100 patients with psoriasis and 30 healthy
      individuals. Gastric secretion was evaluated by means of the fractional test
      (both phases) with histamine stimulation; other diagnostic procedures included
      carbohydrate absorption evaluation (5-gram D-Xylose absorption test), Kamer test
      of fat absorption and evaluation of small intestine bioelectric activity by means
      of electromyography. The patients were followed up within 2 to 3 years. The study
      found negative dynamics in the parameters of gastric secretion, fat and D-xylose
      absorption and small intestine bioelectric activity in patients with psoriasis
      and CO within the 2-3-year follow-up, while the group of dehelmintized patients
      displayed significant improvement of these parameters. Thus, effective
      dehelmintization allowed improvement of alimentary tract functional condition and
      the clinical course of psoriasis.

PMID- 15941145
TI  - [Reduction of cardiovascular risk in primary prophylaxy of coronary heart
      disease].
AB  - The purpose of the study was to evaluate the effects of Allicor, an Allium
      sativum (garlic) preparation with prolonged activity, on 10-year prognostic risk
      of coronary heart disease (CHD), acute myocardial infarction (MI) and sudden
      death in patients with elevated and high risk of CHD. 79 patients with elevated
      and high risk of CHD were included in a double blind randomized placebo
      controlled study. They underwent multifactor evaluation of cardiovascular risk by
      algorithms based on the results of Framingham and Munster studies. Prolonged (12
      months) administration of Allicor significantly reduced the multifactor risk,
      which was demonstrated by a 13.2% (p = 0.005) reduction of prognostic 10-year
      risk of CHD in men, and a 7.1% (p = 0.040) reduction of the same parameter in
      women. Prognostic 10-year risk of MI and sudden death in men was reduced by 26.1%
      (p = 0.025) and did not change significantly in women. In men the main factor of
      cardiovascular risk reduction was the decrease of cholesterol and low-density
      lipoprotein concentration by 23.5 +/- 6.6 mg/dl (p = 0.004), and in women - the
      increase of high-density lipoprotein level by 2.8 +/- 1.5 mg/dl (p = 0.040). The
      results of the study demonstrate that prolonged Allicor therapy can be applied to
      the large category of patients who are in need of atherosclerosis prevention.

PMID- 15941146
TI  - [Antiischemic and metabolic effects of nebivolol and metaprolol CR/XL (betalok
      ZOK) in patients with postinfarction heart dysfunction].
AB  - The purpose of the study was to evaluate anti-ischemic and metabolic effects of
      the cardioselective beta-adrenoblockers nebivolol and retarded metoprolol
      metaprolol CR/XL (betalok ZOK) in patients with postinfarction heart dysfunction,
      associated with type II diabetes mellitus (DM). 40 patients with coronary heart
      disease (CHD), functional class (FC) II-III exertional angina, postinfarction
      left ventricular (LV) dysfunction, and NYHA FC II heart failure, associated with
      type II DM, were randomized into 2 groups. The 20 patients of the 1st group were
      administered nebivolol in a dose of 1.25 to 5 mg per day, the 20 patients of the
      2nd group - betalok ZOK in a dose of 12.5 to 100 mg per day. The course therapy
      lasted 8 weeks. The effects of the treatment were evaluated using paired
      veloergometry, echoCG, and lipid spectrum analysis. The study found that
      nebivolol in a mean dose of 4.2 +/- 0.3 mg per day and betalok ZOK in a dose of
      46.5 +/- 6.2 mg per day reduced the frequency and severety of angina attacks (by
      73.8% and 67.8%, respectively) and daily nitroglycerine uptake (by 78.6% and
      69.1%, respectively), and increased activity tolerance (by 7.9% and 25.3%,
      respectively). None of the preparations displayed any adverse effects on
      carbohydrate exchange and blood lipid spectrum. Nebivolol, unlike betalok ZOK,
      significantly (p = 0.02) reduced triglyceride blood level by 29%. Thus, the new
      generation cardioselective beta1-adrenoblockers nebivolol and metoprolol CR/XL
      (betalok ZOK) provide anti-ischemic and metabolic effects in patients with CHD
      and postinfarction LV dysfunction, associated with type 2 diabetes mellitus.
      Nebivolol is preferable as far as blood lipid spectrum is concerned.

PMID- 15941147
TI  - [Efficacy of nebulizer therapy with acetylcystein in outpatients with chronic
      obstructive lung disease].
AB  - Chronic obstructive lung disease (COLD) is a widespread illness with constantly
      growing mortality. Mucolytic therapy plays a significant role in treatment of
      patients with COLD. The paper contains the results of nebulization with acetyl
      cystein as part of rehabilitation program in outpatients with stable clinical
      course of I-II stage of COLD. The results demonstrated significant clinical
      improvement, as well as positive changes in external respiration parameters (1
      sforced expiratory volume), increase of physical activity tolerance, and
      disappearance of acute inflammation phase reactants in saliva.

PMID- 15941148
TI  - [Abdominal syndrome in patients with coronary heart disease].
AB  - The article discusses diagnostic difficulties in acute abdominal pain. The author
      adduces data on the frequency of diagnostic errors in diagnostics of coronary
      heart disease (CHD) before admission and in the admission department of an urgent
      aid hospital. The analysis of the causes of delayed diagnosis in patients with
      CHD and acute myocardial infarction is exemplified with 3 clinical observations.
      The article also covers ways of prevention of diagnostic errors in patients with
      abdominal pain.

PMID- 15941149
TI  - [A case of diagnostics of dilatational cardiomyopathy with isolated right atrium
      involvement].

PMID- 15941150
TI  - [Giant cell arteritis as the cause of fever of unknown origin].

PMID- 15941151
TI  - [Duodenogastral reflux: moot points and unanswered questions].

PMID- 15941152
TI  - New hips for old! Lessons from the Arabian Nights.

PMID- 15941153
TI  - Early results of metal on metal articulation total hip arthroplasty in young
      patients.
AB  - We report our early experience of 20 cases of metal on metal articulation total
      hip arthroplasty in 19 young patients. Avascular necrosis of the femoral head
      (63%) was the commonest diagnosis for patients undergoing this procedure,
      followed by osteoarthritis (21%). In general, most of the patients were young and
      physically active with an average age of 43.1 years (range, 25 to 58 years). The
      average follow-up period was 18 months (range, 7 to 46 months). The mean total
      Harris Hip Score preoperatively and at final follow-up was 31 points and 89
      points respectively. The mean total Pain Score improved from an average of 11.5
      to 41.1 points at final follow-up. Sixteen (84%) of the patients had a good to
      excellent hip score. There was one dislocation, which stabilized after reduction
      and conservative management. One case of early infection underwent a two-staged
      revision.

PMID- 15941154
TI  - Objective triceps muscle strength measurement using computerized adaptation.
AB  - In our centre the non-availability computerized exercise machines limits the
      objective monitoring of strength rehabilitation. We undertook this research
      programme to objectively measure triceps muscle strength by interfacing NORSK-Gym
      machine with accelerometer and positional transducers to a computer. This data
      was tabulated and processed using Microsoft Excel. The positional transducer was
      first calibrated and it showed an excellent Pearson Correlation Coefficients
      against a standard metric reading (r = 0.9999). Peak Force was used as a test
      parameter for isotonic triceps muscle strength measurements. The criterion
      referenced validity was established as the peak forces measured using the
      accelerometer and positional transducer demonstrated identical Peak Forces (r =
      0.94). Analysis of our mean Peak Force measurements using non-biological force as
      well as the intra-individual reproducibility demonstrated excellent Pearson
      Correlation Coefficients (r) = 0.982-0.998 and 0.929-0.972 respectively. This
      computerized adaptation of the NORSK-Gym machine produced an objective, valid and
      reproducible triceps muscle strength measurement.

PMID- 15941155
TI  - Coronal plane and apical vertebral rotation correction of adolescent idiopathic
      scoliosis with multisegmented hook-rod system--a retrospective review.
AB  - Between April 1998 and December 1999, thirty patients with Idiopathic Scoliosis
      were operated with Multisegmented Hook-Rod System. These patients were operated
      at the mean age of 16 years and were followed up for a mean of 22.3 months (range
      13-34 months). Seven patients had anterior release to increase the curve
      flexibility followed by second stage posterior instrumentation on the same day.
      The average operating time for a posterior instrumentation alone and anterior
      release combined with posterior instrumentation were 270 minutes and 522 minutes
      respectively. The average blood loss was 2.2 litres for posterior instrumentation
      alone and 3.3 litres for single day anterior release and posterior surgery. The
      mean preoperative Cobb's angle was 70 degrees. The mean immediate postoperative
      and final follow up Cobb's angles were 38 and 42 degrees, which represented an
      average coronal plane correction of 46.7% and 40.0% respectively. The mean
      preoperative apical vertebral rotation was 25 degrees, which improved to 15
      degrees after the operation. At final follow up, the mean apical vertebra
      rotation was 20 degrees, which represented a mean apical vertebral rotation
      correction of 20%. Complications of the procedure included one transient
      neurological deficit, one infection, one graft site infection and one case of
      screw cut out. We were able to obtain satisfactory correction of idiopathic
      scoliosis with the Multisegmented Hook-Rod System.

PMID- 15941156
TI  - The epidemiology of shoulder dislocations in Malaysia.
AB  - The case notes of 102 patients (117 shoulder dislocations) were reviewed
      retrospectively to improve the understanding of the epidemiology of this common
      injury. Eighty-one dislocations were primary and 36 dislocations were second or
      recurrent dislocations. The age distribution was characterized by a peak in male
      patients aged between 21-30 years. The mean age for males was 30.5 years and 47.7
      years for females. The male:female ratio in first time dislocations was 5:2,
      while it was 5:1 in recurrent dislocations. Ninety-eight percent were anterior
      dislocations and 2% were posterior dislocations. Greater tuberosity fractures
      were found in 17 patients and almost half of these patients were aged between 41
      50 years. The most common cause of first time dislocation was a direct blow or
      fall onto the shoulder, accounting for 42 patients (55%). The majority of these
      patients were aged 40 years and above. Next common cause was motor vehicle
      accident which occurred mostly in the younger age group. Dislocations due to
      sporting injuries accounted for only 5.3% of all first time dislocations. Nearly
      97% were successfully reduced without a general anaesthesia. Seventy-seven
      percent of the patients had their shoulders immobilized after reduction, mostly
      with body strapping only. Fifteen patients (14.7%) were referred for
      physiotherapy for stiffness. Few operations were performed for recurrent
      dislocations but surgery does not appear to be well accepted as yet by our
      patients.

PMID- 15941157
TI  - Osteosarcoma: the outcome of limb salvage surgery.
AB  - We reviewed the surgical and oncological management 23 consecutive patients with
      osteosarcoma of the long bones to determine the outcome of limb salvage technique
      performed in our centre. All patients received neoadjuvant chemotherapy. There
      were 15 males and 8 females with a mean age at diagnosis of 19 years (9 to 36).
      The median follow-up was 30 months (10 to 60). Fifteen had lesion around the knee
      joint followed by three in the proximal humerus, two in distal humerus, two in
      the pelvis, and one in the distal tibia. Six patients presented with lung
      metastases at diagnosis. We performed limb salvage surgery to control local
      disease in 16 patients and amputation in 7. The resection margins of the primary
      lesion were adequate and free of tumour cells in all patients. Local recurrence
      developed in 1 patient of limb salvage group. The overall median survival was 22
      months and actuarial survival was 52% at 3 years. Eleven patients died of
      pulmonary metastases within 2 years of follow-up. Median survival of the limb
      salvage surgery group was 30 months compared to 6 months in the amputation group.
      As per our experience, limb salvage technique is a feasible option in extremity
      osteosarcoma without compromising survival.

PMID- 15941158
TI  - Early complication following long bone reconstruction using vascularised fibula
      graft.
AB  - Long bone reconstruction using vascularized fibula graft is becoming more popular
      despite the difficulties and its post-operative complications. We reviewed our
      early experience dealing with vascularized fibula graft for the management of
      massive long bone defect. Thirteen patients had undergone long bone
      reconstruction using vascularized fibula graft. Early complications that had been
      encountered include superficial wound infection (23%), transient common peroneal
      nerve palsy (23%), stage 1 bed sore (7.7%), anastomotic venous thrombosis
      (30.8%), DIVC (15.4%), flap loss and amputation (7.7%), and reactive psychiatric
      problem (7.7%). The early complications following this procedure are comparable
      with other major orthopaedic surgery and most of them are minor and treatable.
      The complication rates are also comparable with similar surgery done elsewhere.

PMID- 15941159
TI  - Treatment for flexion contracture of the knee during Ilizarov reconstruction of
      tibia with passive knee extension splint.
AB  - Joint stiffness is one of the complications of limb procedure. It developes as a
      result of failure of knee flexors to lengthen in tandem with the bone, especially
      when there is inadequate physical therapy to provide active and passive
      mobilization of the affected joint. We are reporting four patients who developed
      fixed flexion contracture of their knees during bone lengthening procedure for
      the tibia with Ilizarov external fixator. Three of them were treated for
      congenital pseudoarthrosis and one was for fibular hemimelia. None of them were
      able to visit the physiotherapist even on a weekly basis. A splint was
      constructed from components of Ilizarov external fixator and applied on to the
      existing frame to passively extend the affected knee. Patients and their family
      members were taught to perform this exercise regularly and eventually near
      complete correction were achieved. With this result, we would like to recommend
      the use of this "Passive Knee Extension Splint" to avoid knee flexion Contracture
      during limb lengthening procedures with Ilizarov external fixators.

PMID- 15941160
TI  - Versatility of the latissimus dorsi flap in upper limb salvage tumour surgery.
AB  - Reconstructive surgeons often encounter complex soft tissue and skeletal defects
      following oncological surgery. Soft tissue defects after wide resection in upper
      extremities posses a difficult challenge to find adequate tissue for
      reconstructing these defects. Paucity of local tissues dictates the requirement
      of loco-regional or distant flaps for these complex soft tissue defects which
      often exposes tendons, bones, nerves and joints. The latissimus dorsi muscle is a
      near ideal flap for the reconstruction because of the long neurovascular pedicle,
      ease of mobilization and its expendability. It can be rotated, with or without
      overlying skin, to cover soft tissue defects of the shoulder arm and elbow. Due
      to the large size of the muscle, it can be used to resurface the soft tissue
      defects and cover all major structures. Eleven consecutive cases were reviewed in
      which latissimus dorsi myocutaneous flap was used to reconstruct soft tissue
      defects of the upper limb following radical tumor resection. Flap survival was
      100% with nominal donor site morbidity.

PMID- 15941161
TI  - A modified method of traction for young children with congenital dislocation of
      the hip as a preliminary to reduction.
AB  - Many authors agree that preliminary traction prior to closed or open reduction
      for congenital dislocation of the hip is helpful. Different ways of traction have
      been used and each of them has its own advantages and disadvantages. One of the
      problems in the very young child is the difficulty in maintaining a suitable
      traction that is biomechanically effective. We found that using a rocker bed made
      the traction more "user friendly" for the child, the parent and the doctors.

PMID- 15941162
TI  - Ossifying fibromyxoid tumour in a child.
AB  - Ossifying fibromyxoid tumor (OFMT) is a rare benign tumor, most of which occurs
      in adults with localization in the subcutaneous tissue or muscle of the
      extremities. A five-year-old girl presented with a mass in her right upper thigh.
      Due to the large size of the mass (10 x 7 cm), our provisional diagnosis was a
      soft tissue sarcoma. A tru-cut biopsy showed that the lesion was benign. The mass
      was excised and has not recurred since. To the best of our knowledge, this
      patient is the youngest case of OFMT reported in the English literature.

PMID- 15941163
TI  - Sleeve fracture of the patella in a child.
AB  - Sleeve fracture of the inferior pole of the patella is a rare and distinctive
      fracture in children with few published reports. These fractures are frequently
      misdiagnosed and neglected. We highlight a case of a neglected and misdiagnosed
      sleeve fracture of the patella in an eleven-year-old boy. This was initially
      diagnosed as an avulsion fracture of the tibial tubercle. A good outcome was
      achieved after open reduction and internal fixation.

PMID- 15941164
TI  - The rusty knee--pigmented villonodular synovitis.
AB  - Pigmented villonodular synovitis (PVNS) is a distinct but rare clinical entity
      often presents late with a diagnostic difficulty. Its non-specific manifestations
      require exclusion of several chronic inflammatory disorders and other humorous
      lesions but all investigations including highly predictive magnetic resonance
      imaging (MRI) and arthroscopic examination are non-diagnostic demanding
      confirmatory tissue biopsy. A typical case of such lesion is presented to
      highlight some potential difficulties.

PMID- 15941165
TI  - Symptomatic intra-articular ganglion cyst of the knee.
AB  - We are reporting a case of a patient with a symptomatic intra-articular ganglion
      of the knee arising from infrapatellar fat pad. Plain radiograph and Magnetic
      Resonance (MR) images were correlated with arthroscopic examination and
      histological findings. The cyst was removed and post operatively patient regained
      full extension.

PMID- 15941166
TI  - A rare case of chondrosarcoma of the clavicle.
AB  - Although all types of tumour and tumour-like conditions have been described to
      occur in the clavicle, they only contribute to less then 0.5% of all skeletal
      tumours. The incidence of primary chondrosarcoma of the clavicle is extremely
      rare. To our knowledge it has not been reported in Malaysia. We would like to
      highlight the possibility of chondrosarcoma as a differential diagnosis for a
      clavicular lesion.

PMID- 15941167
TI  - Unicameral bone cyst of the calcaneum.
AB  - The calcaneus is not a common site for a unicameral solitary bone cyst. Little is
      known about the etiology and natural history of these lesions. The author reports
      an adult man with a solitary bone cyst of the os calcis which was confirmed
      radiologically and histologically and successfully treated with curretage and
      bone grafting.

PMID- 15941168
TI  - An unusual radiographic presentation of posterior cruciate ligament avulsion
      fracture.
AB  - A case of traumatic posterior cruciate ligament (PCL) avulsion fracture
      presenting with unusual radiographic findings is described. CT scan of the right
      knee showed features suggestive of combined ACL and PCL avulsion fractures.
      Arthroscopic findings showed that the injury was in fact a PCL avulsion fracture
      that was displaced anteriorly so as to mimic an ACL avulsion fracture on CT scan.

PMID- 15941169
TI  - Tarsal tunnel syndrome caused by ganglion.
AB  - We report a case of delayed diagnosis of tarsal tunnel syndrome caused by a
      ganglion arising from the talo-calcaneal joint. Unusually the symptoms were
      mainly due to the lateral planter nerve compression with a positive Tinel's sign.
      A surgical decompression was successful in relieving the dysaesthesia in spite of
      a 7 years history.

PMID- 15941170
TI  - Close fracture complicated by acute haematogenous osteomyelitis.
AB  - This is the first time we encountered a peculiar case of osteomyelitis
      complicating a closed fracture. The patient was a 38 year-old lady who presented
      just like any other patient with a closed fracture of the right femur.
      Intraoperatively we were surprised to find pus from the fracture site. This not
      only changed the surgical management but altered the subsequent outcome as well.

PMID- 15941171
TI  - Resection and reconstruction of retroperitoneal sarcoma of spinal roots.

PMID- 15941172
TI  - Pulmonary metastases of giant cell tumour of the bone.
AB  - The clinical presentation and behaviour of giant cell tumour of bone vary. The
      progression of the disease and metastasis are unpredictable, but the overall
      prognosis is good. Six patients with pulmonary metastases of giant cell tumour
      have been treated at our institution since 1998. This represents 15% of all
      patients treated for giant cell tumour of the bone. Early detection and treatment
      of this tumour is important as complete resection of this tumour have favourable
      prognosis. Multiple lung nodules which preclude resection may remain dormant and
      asymptomatic with systemic chemotherapy.

PMID- 15941174
TI  - [And if the guardian angel was a nurse?].

PMID- 15941173
TI  - Close vs. closed fracture.

PMID- 15941175
TI  - [Theory? Practice?].
AB  - This second article about the difficult balance between academic and professional
      development in pre-European Spain poses the issue of the theory-practice, or
      learning-treatment, relationship as the historical dissolution of the practical
      in the theoretical.

PMID- 15941176
TI  - [From wish to reality].
AB  - The author counterposes the wish to achieve full recognition and professional
      development with the real situation which nurses face daily in their work places
      and how these working conditions and human relationships affect daily life and
      treatment which is provided by nurses to their patients.

PMID- 15941177
TI  - [Nursing, simply complicated].
AB  - From a very young age, we played doctors and nurses. Back then, society was
      positive that a nursing profession existed. Now, is society's vision adequate?
      Evidently not. But, Why does this distortion exist? Fundamentally this occurs
      because the professionals themselves do not have a clear identity regarding their
      profession. And Why is this? Because the education transmitted has important
      lacks, the sanitary system dampens innovation and creativity, there are no
      appropriate leaders, lobbies transform into "wolves", and neither do we have a
      tradition which facilitates association and cooperation amongst professionals.
      These are some of the factors which the author develops in this deep, brave
      analysis about the reality of the nursing profession in order to arrive at the
      conclusion that we must have clear in our minds what nursing power is, a power
      which interacts with the community, and that this is important not only as a
      power in itself but rather as a means to increase the intrinsic value of nursing,
      none other than providing care.

PMID- 15941178
TI  - [Marie Francoise Colliere: the art of caring for lives].
AB  - After the recent death of Madame Colliere, the author, who had a close personal
      and professional relationship with the deceased, writes an article which
      highlights the character, ideas and teachings which this magnificent woman left
      to the nursing profession.

PMID- 15941179
TI  - [On the necessary defense of dignity].
AB  - As a critique to a television program, the author concludes: if the proposed
      values propounded in this television episode being commented on consist in
      ridiculing problems such as sexual dependence and violence committed against
      women, then effectively the program is proposing a society in which "Here no one
      will be able to survive".

PMID- 15941180
TI  - [Mammogram screening: an on-going debate].
AB  - General public mamma-gram screening programs directed at women aged from 50 to 65
      years are a common practice in Spain and other European countries. After more
      than ten years being recognized as early detection programs for breast cancer A
      debate has opened about the effectiveness of mamma-gram screening to reduce the
      number of deaths due to this type of tumor. The author includes a wide
      bibliography and various data bases such as MEDLINE: 1989-2003, CANCERLIT: 1975
      2002, CINAHL: 1982-2003, and EMBASE: 1988-2003; and realizes it is not simple to
      justify mamma-gram screening since there is a great diversity of opinion in
      medical literature.

PMID- 15941181
TI  - [A new system to treat ostomy in Spain].
AB  - Esteem synergy (ConvaTec, S.L., Group Bristol-Myers Squibb) is a new device for
      ostomized patients which displays differential characteristics and combines the
      benefits of the traditional one- and two-piece systems. A cross-sectional,
      multicentric, prospective study was conducted to evaluate the performance of
      Esteem synergy in clinical practice in Spain. 114 investigators participated in
      the study and 591 ostomized patients--colostomy, ileostomy--were included. The
      period of evaluation was 16 weeks. Objectives were defined in terms of
      effectiveness, security, comfort, impact on the quality of life and global
      valuation. The inclusion questionnaire form, the in-hospital evaluation and the
      out-patient evaluation, applied to each patient and developed in a quantitative,
      qualitative and general evaluation of the new system. Results were classified as
      "very good" in all parameters measured, with no differences between the in
      hospital and the out-patients evaluations. The global performance of the dressing
      was valued positively by most of the patients. The device was valued by patients
      like "very good" or "good" in all the evaluations and independently of the scope
      of evaluation. We concluded that Esteem synergy seems to be the suitable system
      to use for ostomized in- and out-patients.

PMID- 15941182
TI  - [Having diabetes without knowing it].
AB  - As part of the activities on the World Day for Diabetes in 2002, nine professors,
      one nurse who teaches about diabetes and 126 nursing students at University
      Schools of Nursing in Barcelona, Lleida, Tarragona, Tortosa and Girona, in
      collaboration with the Association of Diabetics in Catalonia and with the help of
      the Advisory Council for Diabetes in Catalonia participated in a diabetes
      screening campaign on the population residing in Catalonia. This campaign studied
      the prevalence of type two diabetes in a random sample of the Catalan population.
      This campaign also proposed to raise the awareness among the general population
      and among nursing students about the important health consequences diabetes has
      and to increase investigation and social support measures by nurses related to
      diabetes. This study checked 4083 persons and discovered 77 cases of altered
      blood-sugar levels among people who did not know they had diabetes. This finding
      means that there is a 2.2% prevalence of altered blood-sugar levels in the
      population who are not diagnosed diabetics. Professors and student participants
      all gave this experience positive marks and the students' degree of satisfaction
      was very high.

PMID- 15941183
TI  - [Surgical instruments (I). An introduction to surgical instruments].
AB  - In surgical wards, the variety and increasing complexity of techniques used,
      together with the high number of materials and instruments employed, demands that
      professionals who join these wards have a specific professional development
      related to instruments and techniques. In this short series of articles, the
      author shall present distinct manners to gain knowledge about instruments in such
      a way that at the end of this series, professionals who are interested will have
      a guide to help them acquire a deep understanding of surgical instruments, their
      common usage and their specialized characteristics. A bibliography will be
      included with the last article.

PMID- 15941184
TI  - [What kind of community nurse do we want?].

PMID- 15941185
TI  - Fiscal care for the Medicare Modernization Act.

PMID- 15941186
TI  - How can pharmacoeconomics be more useful?

PMID- 15941187
TI  - Assessing potential risks and evaluating expected benefits.
AB  - The recent withdrawal of rofecoxib from the market will have profound and long
      term effects on the methods by which society views, assesses, and monitors risk.
      As is the case with many drugs, the rofecoxib experience was complex from both
      the scientific and regulatory standpoints. A drug is marketed in the United
      States only if its expected benefits outweigh its risks; a recent trend has also
      included several cost-effectiveness considerations in launch decisions, possibly
      spurring further debates on ethical implications. However, a great portion of the
      evidence about actual outcomes of therapies is revealed in the postmarketing
      phase of development. It is unclear how this understanding of treatment benefit
      and harm should actually relate to a specific clinical decision.

PMID- 15941188
TI  - A comparison of clinical effectiveness initiatives.

PMID- 15941189
TI  - Utilization management and noninvasive diagnostic imaging.
AB  - Health care costs are rising at unprecedented rates in the United States, and a
      substantial contributor to these cost increases is a growing dependence on
      diagnostic imaging. Radiologists have become aware of the need for optimal use of
      imaging provided in a cost-effective and timely manner. This article describes a
      program that has reduced inappropriate imaging use by involving both community
      based and academic radiologists in its precertification process.

PMID- 15941190
TI  - The clinical effectiveness initiative: a pharmacy analysis to improve outcomes
      and costs of drug therapy.
AB  - Selecting the most appropriate therapeutic regimens is one of the most complex
      and critical aspects of pharmacy management today, but the process is fraught
      with biases. Clinical pharmacists must offer balanced and unbiased opinions
      concerning therapies that provide the best cost-benefit ratio for their
      organizations. This article describes the use of existing administrative
      databases to develop robust clinical resource utilization data, identify internal
      bias and barriers to efficient drug therapy selection, and devise medical
      management strategies that provide desirable clinical outcomes through cost
      consequence analysis.

PMID- 15941191
TI  - Environmentally smart polymers.
AB  - Much progress has been made in the synthesis of polymers that emulate certain
      naturally occurring polymers and demonstrate exquisite sensitivity to
      environmental factors such as temperature, pH and mechanical stress. This article
      explains how these are finding use in medical technologies such as drug delivery
      and cell-sheet tissue engineering.

PMID- 15941192
TI  - Resolving the challenges of producing small-bore tubing.
AB  - Experience shows that sufficient time and resources must be allocated to writing
      a specification. It is essential to be clear about the intended use of the
      tubing. Once the preliminary specification has been compiled, trial and error is
      often a necessary part of the process of making a successful product. Finally,
      all polymers are affected by the environment and their previous history.

PMID- 15941193
TI  - Solutions to stabilisation issues.
AB  - Proteins employed as diagnostic agents must be kept stable to maintain their
      structure and viability. Multiple strategies to address stabilisation issues are
      presented here.

PMID- 15941194
TI  - In vitro diagnostics industry news.

PMID- 15941195
TI  - Preventing encrustation in indwelling urethral catheters.
AB  - Encrustation is the main problem encountered with indwelling urethral catheters.
      A promising new approach to overcoming this problem is described here, which may
      have implications for catheter design.

PMID- 15941196
TI  - Design as a research development tool.
AB  - The design and development process is due for some innovation. Current practices
      use design as a downstream activity. This article explores how to use it during
      research and development and the benefits this offers companies.

PMID- 15941197
TI  - Preparing for more active market surveillance.
AB  - Competent Authorities are developing increasingly active market surveillance
      programmes. As a result, they are initiating or broadening the scope of
      inspection visits. This article discusses the manner in which some of these
      visits are being conducted and actions that should be taken to prepare for them.

PMID- 15941198
TI  - The benefits of design partnership.
AB  - Collaboration with outside agencies on product design is still often regarded as
      a risky venture. Its advantages, and the advice on getting the most out of a
      design partner described here, suggest it is a good option, particularly for
      small companies.

PMID- 15941199
TI  - Sourcing goes online for medical device manufacturers.

PMID- 15941200
TI  - Electromechanical lancing device for diabetes monitoring.
AB  - Sterility, precision and convenience for users are the important features of
      blood-monitoring devices. This article examines how some of the design challenges
      were met in a novel lancet system.

PMID- 15941201
TI  - France offers good prospects.

PMID- 15941202
TI  - 3D software streamlines more than design.

PMID- 15941203
TI  - Coatings for medical diagnostics.

PMID- 15941205
TI  - Introduction: inorganic and bioinorganic mechanisms.

PMID- 15941206
TI  - Inorganic and bioinorganic solvent exchange mechanisms.

PMID- 15941207
TI  - Ligand substitution reactions at inorganic centers.

PMID- 15941208
TI  - Treatment of substitution and rearrangement mechanisms of transition metal
      complexes with quantum chemical methods.

PMID- 15941209
TI  - Ion pairing in transition-metal organometallic chemistry.

PMID- 15941210
TI  - Chemistry and enzymology of vitamin B12.

PMID- 15941211
TI  - Mode of action of bi- and trinuclear zinc hydrolases and their synthetic
      analogues.

PMID- 15941212
TI  - Kinetics and mechanisms of formation and reactivity of non-heme iron oxygen
      intermediates.

PMID- 15941213
TI  - Reaction mechanisms of mononuclear non-heme iron oxygenases.

PMID- 15941214
TI  - Structure and chemistry of cytochrome P450.

PMID- 15941215
TI  - Theoretical perspective on the structure and mechanism of cytochrome P450
      enzymes.

PMID- 15941216
TI  - Recent advances in transition metal catalyzed oxidation of organic substrates
      with molecular oxygen.

PMID- 15941217
TI  - Mechanistic studies on synthetic Fe-S-based clusters and their relevance to the
      action of nitrogenases.

PMID- 15941218
TI  - Mechanisms of reductive nitrosylation in iron and copper models relevant to
      biological systems.

PMID- 15941219
TI  - Chemistry of peroxynitrites as compared to peroxynitrates.

PMID- 15941220
TI  - Mechanistic aspects of C-H activation by Pt complexes.

PMID- 15941221
TI  - The potential of palladacycles: more than just precatalysts.

PMID- 15941222
TI  - Homogeneous versus heterogeneous self-exchange electron transfer reactions of
      metal complexes: insights from pressure effects.

PMID- 15941223
TI  - Redox chemistry of nickel complexes in aqueous solutions.

PMID- 15941224
TI  - Mechanism of electron transfer in heme proteins and models: the NMR approach.

PMID- 15941225
TI  - Bioinorganic photochemistry: frontiers and mechanisms.

PMID- 15941226
TI  - Theoretical methods of potential use for studies of inorganic reaction
      mechanisms.

PMID- 15941227
TI  - Fabrication of flexible carbon nanotube field emitter arrays by direct microwave
      irradiation on organic polymer substrate.
AB  - Carbon nanotubes (CNTs) were directly synthesized on flexible polymer substrates
      without damage of polymer by microwave irradiation. Cobalt was used as the
      catalysts, and the synthesis was done in the atmospheric pressure with an
      acetylene carbon source. Only 5 s was required for the synthesis of well
      graphitized CNTs. Field emission measurements revealed that this flexible CNT
      field emitter array has a great potential for the flexible field emission
      displays (FEDs).

PMID- 15941228
TI  - Polymer micelle with cross-linked ionic core.
AB  - This work reports the design of polymer micelles with cross-linked ionic cores
      that display high stability. Block ionomer complexes were utilized as a micellar
      template for the synthesis of the cross-linked micelles. Such micelles represent
      hydrophilic nanospheres of core-shell morphology. The core comprises a network of
      the cross-linked polyanions, which is surrounded by the shell of hydrophilic PEO
      chains.

PMID- 15941229
TI  - Cobalt-filled apoferritin for suspended single-walled carbon nanotube growth with
      narrow diameter distribution.
AB  - Cobalt-filled apoferritin (Co-ferritin) was, for the first time, used as a wet
      catalyst for the synthesis of single-walled carbon nanotubes (SWNTs) with narrow
      diameter distribution. Co-ferritins were spin-coated and converted to cobalt
      nanoparticles by calcination. Using chemical vapor deposition, suspended networks
      of SWNTs were formed on pillar-structured substrates. The suspended SWNTs show
      narrow tube diameter distribution with a relatively good graphite structure. By
      virtue of the low diffusion coefficient of cobalt, Co-ferritin might be more
      useful for narrow diameter SWNTs growth than ferritins, which encase iron
      particles.

PMID- 15941230
TI  - Electron propagator calculations show that alkyl substituents alter porphyrin
      ionization energies.
AB  - The effect of alkyl substituents on the four lowest vertical ionization energies
      of porphyrins is determined with ab initio electron propagator calculations on
      porphine and octamethylporphyrin. With the use of the partial third-order
      approximation, predicted ionization energies are in close agreement with recent
      photoelectron spectra. These data and the associated Dyson orbitals, which
      describe changes in electronic structure that accompany photoionization, enable
      assignment of photoelectron spectra and determination of alkyl-induced shifts.
      Hyperconjugation is most evident in the Dyson orbitals associated with the third
      and fourth ionization energies of octamethylporphyrin and is least prominent in
      the Dyson orbital of the second ionization energy. There is a positive
      correlation between the shift in an ionization energy produced by alkyl
      substitution and the degree of hyperconjugation in the associated Dyson orbital.
      Alkyl substitutions, therefore, may be employed to adjust the ionization energies
      of porphyrins and, consequently, their reactivity patterns that depend on charge
      transfer capabilities and disposition to electrophilic attack.

PMID- 15941231
TI  - Absolute configuration of chiral [2.2]paracyclophanes with intramolecular charge
      transfer interaction. Failure of the exciton chirality method and use of the
      sector rule applied to the cotton effect of the CT transition.
AB  - Optically active 4,7-dicyano-12,15-dimethoxy[2.2]paracyclophanes have been
      separated by chiral HPLC and their absolute configurations determined by
      comparison of the experimental and the theoretical VCD spectra. X-ray
      crystallographic structures for both diastereomers are also reported. The
      electronic circular dichroism spectra of these enantiomeric pairs, as chiral
      intramolecular charge-transfer complexes, have been obtained for the first time.
      The exciton coupling method, usually used for determining the absolute
      configuration of chiral molecules, however, did not give a correct prediction for
      the present CT-paracyclophane system. Instead, empirical sector rules for the
      signs of the Cotton effects of the CT transition can be applied for the
      assignment of the absolute configuration.

PMID- 15941232
TI  - Cyclobutenes by platinum-catalyzed cycloisomerization reactions of enynes.
AB  - 1,6-Enynes bearing (electron-rich) aryl substituents on their alkyne moiety
      rearrange to cyclobutene derivatives in the presence of catalytic amounts of
      PtCl2 in toluene. The reaction is significantly accelerated when performed under
      an atmosphere of CO (1 atm), most likely by increasing the electrophilicity of
      the metal template by temporary coordination to this pi-acidic ligand. This
      transformation allows the build up of considerable strain in the products as
      witnessed by the productive formation of tricyclic skeletons, such as 7 or 9.
      Moreover, these products provide evidence for the mechanistic scenario of
      platinum-catalyzed cycloisomerization reactions previously proposed, which are
      thought to proceed via organo-platinum species that mimic the reactivity of metal
      complexed "nonclassical" carbocations.

PMID- 15941233
TI  - Time-resolved resonance Raman observation of the 2-fluorenylnitrenium ion
      reaction with guanosine to form a C8 intermediate.
AB  - Time-resolved resonance Raman spectroscopy was used to directly observe the
      reaction of the 2-fluorenylnitrenium ion with guanosine to produce a C8
      intermediate species. Comparison of the Raman spectra with results of density
      functional theory calculations indicates the C8 intermediate forms two C=N
      conjugated bonds in ring 1 of the guanosine moiety.

PMID- 15941234
TI  - Radical reactions of a stable N-heterocyclic germylene: EPR study and DFT
      calculation.
AB  - The first radical adducts of a stable N-heterocyclic germylene were investigated.
      Novel radical species were produced from a variety of precursors and studied by
      EPR spectroscopy. DFT (B3LYP) calculations of radical adducts of different (C,
      Si, Ge) unsaturated N-heterocyclic divalent species with phenoxyl radical show
      that in the radicals studied the unpaired electron is delocalized over the five
      membered ring and the spin density on the central atoms decreases in the
      following order: C > Si > Ge. These trends can be understood in terms of
      zwitterionic structure of radical adducts.

PMID- 15941235
TI  - Selective cleavage of the C-C bonds of aminoethyl groups, via a multistep
      pathway, by a pincer iridium complex.
AB  - A pincer-ligated iridium complex is found to react with N-ethylamines, HN(Et)R (R
      = cyclohexyl, tert-butyl, ethyl), to give the corresponding iridium isocyanide
      complexes (PCP)Ir(CH3)(H)(CNR) (PCP = kappa3-2,6-(tBu2PCH2)2C6H3). This novel,
      regioselective C-C bond cleavage reaction occurs readily under mild conditions
      (25-45 degrees C). The reaction is shown to proceed via initial dehydrogenation
      of the amine to give the corresponding imine (N-ethylidenealkylamine). The
      ethylidene sp2 C-H bond then undergoes addition to iridium, followed by methyl
      migration.

PMID- 15941236
TI  - One-step synthesis of triethynylvinylmethanes and tetraethynylmethanes by GaCl(3)
      promoted diethynylation of 1,4-enynes and 1,4-diynes.
AB  - The treatment of 1,4-enynes with chlorotriethylsilylacetylene at 130 degrees C in
      the presence of GaCl3 gave triethynylvinylmethanes by the diethynylation at the
      allylic methylene moiety. The addition of 2,6-di(tert-butyl)-4-methylpyridine and
      tert-butyldiphenylsilanol considerably improved the yields of the products by
      reducing the decompositions of the substrates and products. The reaction should
      involve the initial formation of allylgallium from the enynes and GaCl3, where
      GaCl3 activated hydrocarbon C-H to generate a nucleophilic organogallium
      intermediate. Carbometalation with chloroacetylene followed by beta-elimination
      then led to the ethynylated product. Triethynylvinylmethanes were obtained by the
      repeated regioselective ethynylation at the 3-position of the enynes. The
      reaction of allylsilanes with the chloroacetylene also gave
      diethynylvinylmethanes, in which 1,4-enynes were formed in situ by the addition
      elimination of allylgallium formed from allylsilane and GaCl3.
      Tetraethynylmethanes were obtained by reacting 1,4-diynes with the
      chloroacetylene at 150 degrees C. The structure and amount of silanol can be used
      to control the reactivity of GaCl3.

PMID- 15941237
TI  - A potent transactivation domain mimic with activity in living cells.
AB  - Transcriptional coactivator-binding peptoids were isolated from a large
      combinatorial library. One of these molecules is shown to function as a potent
      activation domain surrogate in mammalian cells. Up to a 900-fold increase in
      expression of a Gal4-responsive reporter gene is observed when a steroid
      conjugate of the peptoid is incubated with HeLa cells expressing a Gal4 DNA
      binding domain (DBD)-glucocorticoid receptor ligand-binding domain (GRLBD) fusion
      protein.

PMID- 15941238
TI  - Divergent kinetic control of classical versus ozonolytic lactonization: mechanism
      based diastereoselection.
AB  - A strategy has been developed in which mechanistically distinct lactonization
      reactions are used to prepare diastereomeric delta-lactones relevant to the C1-C9
      fragment of (+)-peloruside A. Depending upon which of two reaction types is used,
      the central (C5) hydroxyl group can be directed to differentiate the C1 versus C9
      termini of pseudosymmetric substrates to provide diastereomeric lactones. Thus,
      the 5-hydroxy-1,9-diester substrate 1 (an azelaic ester) cyclizes under classical
      (acid- or base-catalyzed) lactonization conditions to give a predominance of one
      diastereomer, whereas the 5-hydroxy-1,10-diene congener 2 provides the opposite
      sense of diastereoselectivity when subjected to ozonolytic lactonization (O3,
      MeOH, NaOH, at -78 degrees C). Thus, this under-utilized oxidative transformation
      is mechanistically orthogonal to the classical reaction.

PMID- 15941239
TI  - MauG-dependent in vitro biosynthesis of tryptophan tryptophylquinone in
      methylamine dehydrogenase.
AB  - Tryptophan tryptophylquinone (TTQ) is the prosthetic group of methylamine
      dehydrogenase (MADH) and is synthesized through post-translational modification
      of two endogenous tryptophan residues. This modification involves two oxygenation
      reactions and one cross-linking reaction. It is clearly shown that the
      incorporation of the second oxygen into betaTrp57 and the covalent cross-linking
      of betaTrp57 to betaTrp108 are MauG-dependent processes. These reaction steps are
      severely compromised in vivo when mauG is mutated or deleted. These steps may
      then be catalyzed in vitro upon addition of MauG to the isolated biosynthetic
      intermediates. These results also show that TTQ formation is linked to proper
      assembly of subunits during MADH biosynthesis. Last, these results demonstrate a
      novel function for the c-type heme protein, MauG, which is consistent with its
      atypical physical properties. These results are the first description of an
      enzyme-mediated biosynthesis of a protein-derived cofactor in vitro.

PMID- 15941240
TI  - An anomeric control on remote stereochemistry in the synthesis of spiroketals.
AB  - Evidence for a remarkable anomeric control on the stereoselectivity of a remote
      center is described in this communication.

PMID- 15941241
TI  - 3-center-4-electron bonding in [(silox)2Mo=NtBu]2(mu-Hg) controls reactivity
      while frontier orbitals permit a dimolybdenum pi-bond energy estimate.
AB  - Na/Hg reduction of (silox)2Cl2Mo=NtBu (3) afforded C2h [(silox)2Mo=NtBu]2(mu-Hg)
      (12-Hg), which consists of two distorted trigonal monoprisms with Hg at the each
      apex (d(MoHg) = 2.6810(5) A). Calculations reveal 3c4e bonding in the linear
      MoHgMo linkage that renders 12-Hg susceptible to nucleophilic cleavage. Exposure
      to PMe3 and pyridine rapidly (<5 min) affords (silox)2(tBuN)MoLn (L = PMe3, n = 1
      (1-PMe3); py, n = 2 (1-py2)), while poorer nucleophiles (L = C2H4, 2-butyne)
      yield adducts (e.g., 1-C2H4 and 1-C2Me2) after prolonged heating. The HOMO and
      LUMO of 12-Hg are "stretched" pi and pi* orbitals from which four states arise:
      1Ag (GS), 3Bu, 1Bu, and 1Ag. DeltaE = E(1Bu) - E(3Bu) = 2K, where K is the
      exchange energy. Magnetic studies indicate E(3Bu) - E(1Ag) approximately 550 cm-1
      (calcd 1744 cm-1), and a UV-vis absorption at 10 000 cm-1 is assigned to 1Ag -->
      1Bu, permitting K to be evaluated as 4725 cm-1. With the pi --> pi* transition in
      Schrock's [Mo(NAr)(CH2tBu)(OC6F5)]2 (4) assigned at 528 nm, this estimation
      places its pi-bond energy as {E(pi2 --> pi1pi*1 in 4) - E(1Ag --> 1Bu in 12-Hg)}
      + E(1Ag --> 3Bu in 12-Hg) = 27 kcal/mol.

PMID- 15941242
TI  - Highly regioselective Ir-catalyzed beta-borylation of porphyrins via C-H bond
      activation and construction of beta-beta-linked diporphyrin.
AB  - Highly regioselective borylation of 5,15-diaryl- and 5,10,15-triarylporphyrins
      has been achieved by the reaction with bis(pinacolato)diborane under iridium
      catalysis. Borylated porphyrins are a useful building block for constructing
      porphyrin arrays, hence offering an effective route to beta-functionalized
      porphyrins.

PMID- 15941243
TI  - Photocontrolled microphase separation of block copolymers in two dimensions.
AB  - A novel ABA-type triblock copolymer, where A and B correspond to azobenzene (Az)
      containing polymethacrylate and poly(ethylene oxide) (PEO), respectively, was
      synthesized by atom transfer radical polymerization. Langmuir-Blodgett monolayers
      showed characteristic microphase separation structures depending on the
      isomerization state of the Az unit. The trans-to-cis isomerization induced an
      anisotropic elongation of the domain of the Az polymer parallel to the rod
      maintaining the width. Thus, successful photocontrol of nanostructures formed by
      the block copolymer in the two dimensions was performed. A plausible model for
      the Az packing and PEO conformation is proposed.

PMID- 15941244
TI  - Nano-welding by scanning probe microscope.
AB  - A novel method, nano-welding, analogous to spot welding at the nanoscale level
      using scanning probe microscopy (SPM) is presented. Using SPM oxidation of the
      underlying silicon, single-walled carbon nanotubes (SWNTs) have been immobilized
      to the surface at point sites along their lengths by the nano-welding. It is
      shown that this nano-welding process nearly has no structural damage to the
      SWNTs. This immobilization makes the SPM manipulation of SWNTs controllable and
      desirable, which is helpful for the construction of SWNT-based nanodevices.

PMID- 15941245
TI  - Sensing of antipyretic carboxylates by simple chromogenic calix[4]pyrroles.
AB  - We present a simple, two- or three-step method for the synthesis of chromogenic
      octamethylcalix[4]pyrrole-based (OMCP) sensors for anions. Electrophilic aromatic
      substitution allows for converting the pyrrole moieties of OMCP into a dye. The
      formation of a sensor-anion complex results in partial charge transfer and a
      dramatic change in color. The absorption (UV-vis) and NMR titration experiments
      show that the chromogenic OMCPs sense anions administered as aqueous solutions,
      even at high ionic strength ( approximately 0.1 M NaCl), while displaying
      selectivity for pyrophosphate and carboxylate anions. The experiments with
      polyurethane sensor films show a strong response for aqueous carboxylates, such
      as antipyretics naproxen approximately ibuprofen > salicylate, without being
      biased by bicarbonate or carboxy termini of blood plasma proteins.

PMID- 15941246
TI  - Determining the Mg2+ stoichiometry for folding an RNA metal ion core.
AB  - The folding and catalytic function of RNA molecules depend on their interactions
      with divalent metal ions, such as magnesium. As with every molecular process, the
      most basic knowledge required for understanding the close relationship of an RNA
      with its metal ions is the stoichiometry of the interaction. Unfortunately,
      inventories of the numbers of divalent ions associated with unfolded and folded
      RNA states have been unattainable. A common approach has been to interpret Hill
      coefficients fit to folding equilibria as the number of metal ions bound upon
      folding. However, this approach is vitiated by the presence of diffusely
      associated divalent ions in a dynamic ion atmosphere and by the likelihood of
      multiple transitions along a folding pathway. We demonstrate that the use of
      molar concentrations of background monovalent salt can alleviate these
      complications. These simplifying solution conditions allow a precise
      determination of the stoichiometry of the magnesium ions involved in folding the
      metal ion core of the P4-P6 domain of the Tetrahymena group I ribozyme. Hill
      analysis of hydroxyl radical footprinting data suggests that the P4-P6 RNA core
      folds cooperatively upon the association of two metal ions. This unexpectedly
      small stoichiometry is strongly supported by counting magnesium ions associated
      with the P4-P6 RNA via fluorescence titration and atomic emission spectroscopy.
      By pinpointing the metal ion stoichiometry, these measurements provide a critical
      but previously missing step in the thermodynamic dissection of the coupling
      between metal ion binding and RNA folding.

PMID- 15941247
TI  - In situ synthesis of temperature-sensitive hollow microspheres via interfacial
      polymerization.
AB  - In this communication, a novel one-pot synthetic strategy for preparing hollow
      PNIPAM microspheres via an interfacial polymerization approach at the interface
      of an inverse W/O emulsion has been proposed and demonstrated. The results show
      that the prepared PNIPAM microspheres have real empty core and polymer shell
      structure, with a size range of 1-3 mum. The hollow microspheres experienced a
      reversible swelling and deswelling process by mediating the temperature below and
      above the lower critical solution temperature (LCST) of the PNIPAM. The new
      approach not only provided a unique technical pathway to prepare hollow PNIPAM
      microspheres in situ under mild reaction conditions but also opened a platform
      for helping to understand the mechanism of diffusion, migration of the PNIPAM at
      an oil/water interface above its LCST, and the polymer layer formation mechanism
      as well.

PMID- 15941248
TI  - An entry to a chiral dihydropyrazole scaffold: enantioselective [3 + 2]
      cycloaddition of nitrile imines.
AB  - We have developed a versatile strategy to access dihydropyrazoles in highly
      enantioenriched form. Dipolar cycloaddition of electron-deficient acceptors and
      in situ-generated nitrile imines proceeds with high regio- and enantioselectivity
      using 10 mol % chiral Lewis acid catalyst. A variety of dihydropyrazoles that
      incorporate functionality for further manipulation have been prepared.

PMID- 15941249
TI  - A simple structural-based approach to prevent aminoglycoside inactivation by
      bacterial defense proteins. Conformational restriction provides effective
      protection against neomycin-B nucleotidylation by ANT4.
AB  - Herein, we describe how the conformational differences exhibited by
      aminoglycosides in the binding pockets of the ribosome and those enzymes involved
      in bacterial resistance can be exploited in the design of new antibiotic
      derivatives with improved activity in resistant strains. The simple modification
      shown in the figure, leading to the conformationally restricted 5, provides an
      effective protection against aminoglycoside inactivation by Staphylococcus aureus
      ANT4, both in vivo and in vitro.

PMID- 15941250
TI  - Polarized emission of individual self-assembled oligo(p-phenylenevinylene)-based
      nanofibers on a solid support.
AB  - We have prepared 5 nm diameter, micrometer long tetra(p-phenylenevinylene) (OPV)
      based nanofibers on a graphite surface. The fluorescence emission of an
      individual fiber shows a profound polarization over its entire length that
      directly corresponds to its orientation on the substrate. Quantitative analysis
      of the fluorescence polarization, including the depolarizing effect of the
      underlying graphite, evidences the high degree of organization within chiral
      fibers with the OPV molecules perpendicular to the fiber axis. The control of the
      internal order within self-assembled fibers, and the ability to measure it, is a
      crucial step to obtain uniform organic fibers that can be applied in nanosized
      electronics at room temperature.

PMID- 15941251
TI  - Are C-H groups significant hydrogen bonding sites in anion receptors? Benzene
      complexes with Cl-, NO3-, and ClO4-.
AB  - Theoretical calculations,examination of crystallographic data, and experimental
      binding energies suggest that even in the absence of electron-withdrawing
      substituents, simple arenes such as benzene form hydrogen bonds with anions that
      can exceed 50% of the strength of those formed by O-H and N-H groups. Thus, when
      present in a receptor, even moderately acidic C-H groups can significantly
      enhance the anion binding affinity and they should be considered as additional
      binding sites within the host cavity.

PMID- 15941252
TI  - Controlled self-assembly triggered by olefin metathesis: cross-linked graphitic
      nanotubes from an amphiphilic hexa-peri-hexabenzocoronene.
AB  - Acyclic diene metathesis (ADMET) in CH2Cl2 of a Gemini-shaped nonionic
      hexabenzocoronene amphiphile (2), bearing triethylene glycol chains with terminal
      allylic functionalities, resulted in spontaneous formation of graphitic nanotubes
      with a cross-linked surface. Without ADMET, 2 did not self-assemble to form a
      tubular structure due to a high solubility in CH2Cl2. Although 2 formed nanotubes
      in THF, ADMET on the surface of the preformed nanotubes in THF proceeded only
      sluggishly and resulted in partial disruption of the tubular structure. The cross
      linked nanotubes showed a softening temperature (244 degrees C) higher than that
      of the uncross-linked version (195 degrees C) and preserved their hollow
      structure much longer upon heating.

PMID- 15941253
TI  - GaN:ZnO solid solution as a photocatalyst for visible-light-driven overall water
      splitting.
AB  - Photocatalytic overall water splitting has been studied extensively from the
      viewpoint of solar energy conversion. Despite numerous attempts, none have
      yielded satisfactory results for the development of photocatalysts, which work
      under visible light irradiation to efficiently utilize solar energy. We report
      here the first example of visible-light-driven overall water splitting on a novel
      oxynitride photocatalyst, a solid solution of GaN and ZnO with a band gap of 2.58
      2.76 eV, modified with RuO2 nanoparticles. In contrast to the conventional non
      oxide photocatalysts, such as CdS, the solid solution is stable during the
      overall water splitting reaction. This is the first example of achieving overall
      water splitting by a photocatalyst with a band gap in the visible light region,
      which opens the possibility of new non-oxide-type photocatalysts for energy
      conversion.

PMID- 15941254
TI  - Asymmetric hydrogenation of tert-alkyl ketones.
AB  - A combined system of RuCl2(tolbinap)(pica) and an alkaline or organic phosphazene
      base catalyzes asymmetric hydrogenation of sterically congested tert-alkyl
      ketones (TolBINAP = 2,2'-bis(di-4-tolylphosphino)-1,1'-binaphthyl, PICA = alpha
      picolylamine). Hydrogenation with RuH(eta1-BH4)(tolbinap)(pica) does not require
      any strong base. Alcoholic solvents strongly affect the catalytic efficiency. The
      reaction proceeds smoothly in ethanol under 1-20 atm of H2 and at room
      temperature with a substrate to catalyst molar ratio of up to 100 000. Various
      aliphatic, aromatic, heteroaromatic, and olefinic tert-alkyl ketones are
      convertible to the corresponding chiral carbinols in high enantiomeric purity.
      Olefinic and heteroaromatic functions are left intact. Certain cyclic ketones are
      also usable. The mode of enantioface selection is consistent and predictable.

PMID- 15941255
TI  - A new design for light-breakable polymer micelles.
AB  - A new and general design strategy is presented for amphiphilic block copolymers
      whose micellar aggregates can be dissociated by light. A diblock copolymer
      composed of hydrophilic poly(ethylene oxide) (PEO) and a hydrophobic
      polymethacrylate bearing pyrene pendant groups (PPy) was synthesized using ATRP.
      Upon UV light irradiation of polymer micellar solutions, the photosolvolysis of
      pyrene moieties results in their detachment from the polymer and converts the
      hydrophobic PPy block into hydrophilic poly(methacrylic acid). This effect leads
      to complete dissociation of polymer micelles.

PMID- 15941256
TI  - Synthesis of (-)-tetracycline.
AB  - We describe a convergent, enantioselective synthesis of (-)-tetracycline (1) from
      benzoic acid (17 steps, 1.1% yield). Benzoic acid was transformed into the AB
      precursor 2 in 10 steps (11% yield), as previously described, and the latter
      compound was activated toward Diels-Alder cycloaddition by the introduction of an
      alpha-phenylthio group (two steps, 66% yield). Heating of the resulting alpha
      (phenylthio)enone (3) with the triethylsilyloxybenzocyclobutene derivative 4 at
      85 degrees C gave the endo-Diels Alder adduct 5 in 64% yield. Deprotection and
      oxidation of the latter intermediate gave the 2-(phenylthio)-1,3-diketone 7,
      which was oxidized with m-chloroperoxybenzoic acid in the presence of
      trifluoroacetic acid. The sulfoxide intermediate(s) formed eliminated upon
      warming to 35 degrees C to give the anyhydrotetracycline derivative 8.
      Intermediate 8 underwent spontaneous autoxidation at 23 degrees C to form the
      hydroperoxide keto-9 stereoselectively. Without isolation, hydrogenolysis of 9 in
      the presence of palladium black gave (-)-tetracycline (42% yield from 7),
      indistinguishable from an authentic sample.

PMID- 15941257
TI  - Cobalt-catalyzed hydroazidation of olefins: convenient access to alkyl azides.
AB  - Conversion of olefins to azides was achieved with high Markovnikov selectivity
      for a broad range of alkenes using 6 mol % Co(BF4).6H2O and ligand 1, with 3
      equiv of TsN3 as nitrogen source and simple silanes (PhSiH3, TMDSO).

PMID- 15941258
TI  - Bundle-like assemblies of cadmium hydroxide nanostrands and anionic dyes.
AB  - Molecularly flat and extremely long bundle-like assemblies were prepared from
      cadmium hydroxide nanostrands and polysulfonated dyes. The dye molecules were
      regularly aligned along with the nanostrands, as confirmed by electron
      microscopies and UV-vis absorption spectroscopy. Strong electrostatic interaction
      between the two components was useful to control the fibrous morphologies and
      optical properties of these organic/inorganic nanocomposites.

PMID- 15941259
TI  - Total synthesis of salinosporamide A.
AB  - Total synthesis of potent proteasome inhibitor salinosporamide A (1) has been
      accomplished, which features strictly substrate-controlled operations starting
      with the only chiral center of (R)-pyroglutamic acid. The consecutive quaternary
      carbons within 1 have been efficiently constructed by manipulation of two
      intramolecular reactions: (1) carbonate-mediated internal acylation of imidate
      ester (4 --> 14) and (2) selenocyclization of aldehyde to exocyclic methylene
      group (5 --> 18).

PMID- 15941260
TI  - Sulfidative purification of carbon nanotubes integrated in transistors.
AB  - We demonstrate a simple purification method of carbon nanotubes via sulfidation
      reaction of carbon, C + 2S --> CS2, to selectively remove carbonaceous impurities
      from nanotubes. The sulfidative purification of carbon nanotubes integrated in
      field-effect transistors results in a dramatic improvement of switching
      characteristics due to removal of carbonaceous impurities.

PMID- 15941261
TI  - Selective surface activation of a functional monolayer for the fabrication of
      nanometer scale thiol patterns and directed self-assembly of gold nanoparticles.
AB  - Application of a voltage bias between the tip of an atomic force microscope (AFM)
      and a silicon substrate causes the localized modification of a specially designed
      self-assembled monolayer (SAM), transforming a surface-bound thiocarbonate into a
      surface-bound thiol. The resulting surface-bound thiols are used to direct the
      patternwise self-assembly of gold nanoparticles (AuNPs). This methodology is
      applied to deposit individual AuNPs onto a surface with nanometer precision and
      to produce 10 nm lines of closely spaced AuNPs that are a single nanoparticle in
      width.

PMID- 15941262
TI  - Titanosilicate molecular sieve for size-screening photocatalytic conversion.
AB  - Titanosilicate molecular sieves, when activated by ultraviolet light irradiation
      in water in the presence of molecular oxygen, catalyze a conversion of molecules
      having a size close to the pore of the catalysts but are inactive for molecules
      having much larger or smaller size. This unprecedented size-screening
      photocatalytic activity is triggered by a combination of H2O-induced shortened
      lifetime of active species (charge-transfer excited state of tetrahedrally
      coordinated titanium oxide) and restricted diffusion of a molecule inside the
      pore. This catalytic property demonstrates a potential utility of the catalyst
      for selective transformation of molecules that is associated with a size
      reduction of molecules, so-labeled "molecular shave" transformation.

PMID- 15941263
TI  - Helical rosette nanotubes with tunable stability and hierarchy.
AB  - The design of nanostructured materials with tunable dimensions and properties
      that maintain their structural integrity under physiological conditions is a
      major challenge in biomedical engineering and nanomedicine. Helical rosette
      nanotubes (HRN) are a new class of materials produced through a hierarchical self
      assembly process of low molecular weight synthetic organic modules in water.
      Here, we describe a synthetic strategy to tune their stability and hierarchy by
      preorganization of the self-assembling units, control of net charge per unit of
      nanotube surface area, amphiphilicity, and number of H-bonds per self-assembling
      module, and through peripheral steric (de)compression. Using these criteria, HRNs
      with tunable stability and hierarchical architecture were produced from self
      assembling modules that (a) persist as individual molecules in solution, (b) self
      assemble into HRN but denature at high temperature (<85 degrees C), (c) self
      assemble into HRN whose structural integrity persists even in boiling water (>95
      degrees C), and (d) self-assemble into well-dispersed short nanotubes, long
      nanotubes, ribbons, or superhelices. Given the biocompatibility, synthetic
      accessibility, and chemical and physical tunability of these materials, numerous
      applications in biomedical engineering, materials science, and nanoscience and
      technology are envisioned.

PMID- 15941264
TI  - Enzyme control of small-molecule coordination in FosA as revealed by 31P pulsed
      ENDOR and ESE-EPR.
AB  - FosA is a manganese metalloglutathione transferase that confers resistance to the
      broad-spectrum antibiotic fosfomycin, which contains a phosphonate group. The
      active site of this enzyme consists of a high-spin Mn(2+) ion coordinated by
      endogenous ligands (a glutamate and two histidine residues) and by exogenous
      ligands, such as substrate fosfomycin. To study the Mn(2+) coordination
      environment of FosA in the presence of substrate and the inhibitors
      phosphonoformate and phosphate, we have used (31)P pulsed electron-nuclear double
      resonance (ENDOR) at 35 GHz to obtain metrical information from (31)P-Mn(2+)
      interactions. We have found that continuous wave (CW) (31)P ENDOR is not
      successful in the study of phosphates and phosphonates coordinated to Mn(2+).
      Parallel studies of phosph(on)ate binding to the Mn(2+) of FosA and to aqueous
      Mn(2+) ion disclose how the enzyme modifies the coordination of these molecules
      to the active site Mn(2+). Through analysis of (31)P hyperfine parameters derived
      from simulations of the ENDOR spectra we have determined the binding modes of the
      phosph(on)ates in each sample and discerned details of the geometric and
      electronic structure of the metal center. The (31)P ENDOR studies of the protein
      samples agree with, or improve on, the Mn-P distances determined from crystal
      structures and provide Mn-phosph(on)ate bonding information not available from
      these studies. Electron spin echo electron paramagnetic resonance (ESE-EPR)
      spectra have also been recorded. Simulation of these spectra yield the axial and
      rhombic components of the Mn(2+) (S = (5)/(2)) zero-field splitting (zfs) tensor.
      Comparison of structural inferences based on these zfs parameters both with the
      known enzyme structures and the (31)P ENDOR results establishes that the time
      honored procedure of analyzing Mn(2+) zfs parameters to describe the coordination
      environment of the metal ion is not valid or productive.

PMID- 15941265
TI  - 157 nm pellicles (thin films) for photolithography: mechanistic investigation of
      the VUV and UV-C photolysis of fluorocarbons.
AB  - The use of 157 nm as the next lower wavelength for photolithography for the
      production of semiconductors has created a need for transparent and radiation
      durable polymers for use in soft pellicles, the polymer films which protect the
      chip from particle deposition. The most promising materials for pellicles are
      fluorinated polymers, but currently available fluorinated polymers undergo
      photodegradation and/or photodarkening upon long term exposure to 157 nm
      irradiation. To understand the mechanism of the photodegradation and
      photodarkening of fluorinated polymers, mechanistic studies on the photolysis of
      liquid model fluorocarbons, including perfluorobutylethyl ether and perfluoro-2H
      3-oxa-heptane, were performed employing UV, NMR, FTIR, GC, and GC/MS analyses.
      All hydrogen-containing compounds showed decreased photostability compared to the
      fully perfluorinated compounds. Irradiation in the presence of atmospheric oxygen
      showed reduced photostability compared to deoxygenated samples. Photolysis of the
      samples was performed at 157, 172, 185, and 254 nm and showed only minor
      wavelength dependence. Mechanisms for photodegradation of the fluorocarbons are
      proposed, which involve Rydberg excited states. Time-dependent density functional
      theory has been used to predict the excitation spectra of model compounds.

PMID- 15941267
TI  - Mechanistic study of the SmI2/H2O/amine-mediated reduction of alkyl halides:
      amine base strength (pKBH+) dependent rate.
AB  - The kinetics of the SmI(2)/H(2)O/amine-mediated reduction of 1-chlorodecane has
      been studied in detail. The rate of reaction is first order in amine and 1
      chlorodecane, second order in SmI(2), and zero order in H(2)O. Initial rate
      studies of more than 20 different amines show a correlation between the base
      strength (pK(BH+) of the amine and the logarithm of the observed initial rate, in
      agreement with Bronsted catalysis rate law. To obtain the activation parameters,
      the rate constant for the reduction was determined at different temperatures (0
      to +40 degrees C, DeltaH++ = 32.4 +/- 0.8 kJ mol(-1), DeltaS++ = -148 +/- 1 J K(
      1) mol(-1), and DeltaG++(298K) = 76.4 +/- 1.2 kJ mol(-1)). Additionally, the
      (13)C kinetic isotope effects (KIE) were determined for the reduction of 1
      iododecane and 1-bromodecane. Primary (13)C KIEs (k(12)/k(13), 20 degrees C) of
      1.037 +/- 0.007 and 1.062 +/- 0.015, respectively, were determined for these
      reductions. This shows that cleavage of the carbon-halide bond occurs in the rate
      determining step. A mechanism of the SmI(2)/H(2)O/amine-mediated reduction of
      alkyl halides is proposed on the basis of these results.

PMID- 15941266
TI  - Scan-rate-dependent melting transitions of interleukin-1 receptor (type II):
      elucidation of meaningful thermodynamic and kinetic parameters of aggregation
      acquired from DSC simulations.
AB  - The role of thermal unfolding as it pertains to thermodynamic properties of
      proteins and their stability has been the subject of study for more than 50
      years. Moreover, exactly how the unfolding properties of a given protein system
      may influence the kinetics of aggregation has not been fully characterized. In
      the study of recombinant human Interleukin-1 receptor type II (rhuIL-1R(II))
      aggregation, data obtained from size exclusion chromatography and differential
      scanning calorimetry (DSC) were used to model the thermodynamic and kinetic
      properties of irreversible denaturation. A break from linearity in the initial
      aggregation rates as a function of 1/T was observed in the vicinity of the
      melting transition temperature (T(m) approximately 53.5 degrees C), suggesting
      significant involvement of protein unfolding in the reaction pathway. A scan-rate
      dependence in the DSC experiment testifies to the nonequilibrium influences of
      the aggregation process. A mechanistic model was developed to extract meaningful
      thermodynamic and kinetic parameters from an irreversibly denatured process. The
      model was used to simulate how unfolding properties could be used to predict
      aggregation rates at different temperatures above and below the T(m) and to
      account for concentration dependence of reaction rates. The model was shown to
      uniquely identify the thermodynamic parameters DeltaC(P) (1.3 +/- 0.7 kcal/mol
      K), DeltaH(m) (74.3 +/- 6.8 kcal/mol), and T(m) with reasonable variances.

PMID- 15941268
TI  - Adsorption of acrylonitrile on diamond and silicon (001)-(2 x 1) surfaces:
      effects of dimer structure on reaction pathways and product distributions.
AB  - Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron
      spectroscopy (XPS) are used to compare the reaction of acrylonitrile with Si(001)
      and C(001) (diamond) surfaces. Our results show that reaction with Si(001) and
      C(001) yield very different product distributions that result from fundamental
      differences in the ionic character of these surfaces. While acrylonitrile reacts
      with the C(001) surface via a [2 + 2] cycloaddition reaction in a manner similar
      to nonpolar molecules such as alkenes and disilenes, reaction with the Si(001)
      surface occurs largely through the nitrile group. This work represents the first
      experimental example of how differences in dimer structure lead to very different
      chemistry for C(001) compared to that for Si(001). The fact that Si(001) reacts
      with the strongly polar nitrile group of acrylonitrile indicates that the
      zwitterionic character of this surface controls its reactivity. C(001) dimers, on
      the other hand, behave more like a true molecular double bond, albeit a highly
      strained one. Consequently, while alternative strategies will be necessary for
      chemical modification of Si(001), traditional schemes from organic chemistry for
      functionalization of alkenes and disilenes may be available for building
      molecular layers on C(001).

PMID- 15941269
TI  - Catalytic asymmetric vinylation and dienylation of ketones.
AB  - A solution to the long-standing problem of catalytic asymmetric vinylation of
      ketones is reported. Vinylzinc reagents are generated via hydrozirconation of
      terminal alkynes followed by transmetalation to zinc. In the presence of our
      catalyst, which is formed in situ from a bis(sulfonamide) diol ligand (1) and
      titanium tetraisopropoxide, the vinylzinc reagent undergoes 1,2-addition to a
      variety of ketones and enones with enantioselectivities (typically >90%) and high
      yields. This method is tolerant of functional groups, including alkyl, aryl and
      vinyl halides, esters, silyl protected alcohols, sulfides, and alkenes. Thus,
      enantioenriched tertiary allylic alcohols bearing a variety of functional groups
      can be prepared. It has also been found that 2,2-disubstituted vinylzinc
      reagents, substitution patterns not accessible through hydrozirconation, can be
      added to ketones with high enantioselectivities to generate trisubstituted
      allylic alcohols. Furthermore, we have developed an asymmetric addition of dienyl
      groups to ketones in the presence of our catalyst. This method enables the
      synthesis of dienols in high yields with enantioselectivities as high as 94%.

PMID- 15941270
TI  - Synthesis, structure, and 19F NMR spectra of 1,3,7,10,14,17,23,28,31,40
      C60(CF3)10.
AB  - A significant improvement in the selectivity of fullerene trifluoromethylation
      reactions was achieved. Reaction of trifluoroiodomethane with [60]fullerene at
      460 degrees C and [70]fullerene at 470 degrees C in a flow reactor led to
      isolation of cold-zone-condensed mixtures of C60(CF3)n and C70(CF3)n compounds
      with narrow composition ranges: 6 < or = n < or = 12 for C(60)(CF3)n and 8 < or =
      n < or = 14 for C70(CF3)n. The predominant products in the C(60) reaction, an
      estimated 40+ mol % of the cold-zone condensate, were three isomers of
      C60(CF3)10. Two of these were purified by two-stage HPLC to 80+% isomeric purity.
      The third isomer was purified by three-stage HPLC to 95% isomeric purity.
      Thirteen milligrams of this orange-brown compound was isolated (5% overall yield
      based on C60, and its C1-symmetric structure was determined to be
      1,3,7,10,14,17,23,28,31,40-C60(CF3)10 by X-ray crystallography. The CF3 groups
      are either meta or para to one another on a p-m-p-p-p-m-p-m-p ribbon of edge
      sharing C6(CF3)2 hexagons (each pair of adjacent hexagons shares a common CF3
      group). The selectivity of the C70 reaction was even higher. The predominant
      product was a single C70(CF3)10 isomer representing >40 mol % of the cold-zone
      condensate. Single-stage HPLC led to the isolation of 12 mg of this brown
      compound in 95% isomeric purity (27% overall yield based on converted C70. The
      new compounds were characterized by EI or S(8)-MALDI mass spectrometry and 2D
      COSY 19F NMR spectroscopy. The NMR data demonstrate that through-space coupling
      via direct overlap of fluorine orbitals is the predominant contribution to J(FF)
      values in these and most other fullerene(CF3)n compounds.

PMID- 15941271
TI  - Dissipation of electronic excitation energy within a C60 [6:0]-hexaadduct
      carrying 12 pyropheophorbide a moieties.
AB  - The synthesis and photophysical studies of a fullerene [6:0]-hexaadduct that
      carries 12 pyropheophorbide a units are reported. The synthesis started with the
      malonate 1, which was coupled under template conditions to C(60)() to give the
      hexaadduct 2. After removal of the protecting group with acid the dodecakis amino
      substituted precursor compound 3 was generated. 3 was not isolated but directly
      reacted with the N-succinimid ester 4 of pyropheophorbide a (5), which delivered
      the desired fullerene [6:0]-hexaadduct 6 in excellent yield. The photophysical
      properties of 6 were studied and compared with those of the fullerene [5:1]
      hexaadduct 7 with six pyropheophorbide a groups and the bispyropheophorbide a
      fullerene [5:1]-hexaadduct 8. The pyropheophorbide a units in 6 undergo after
      light absorption very efficient energy transfer as well as partly excitonic
      interaction. The last process results in formation of energy traps, which could
      be resolved experimentally. Compared to the reference compounds 7 and 8, 6 has a
      higher probability of trap formation due to a higher local concentration of dye
      molecules and shorter distances between them. As a consequence, the excitation
      energy is delivered rapidly (within 23 ps) to the traps, resulting in decreases
      of the fluorescence, intersystem crossing, and singlet oxygen quantum yields in
      comparison with the values of the reference compounds.

PMID- 15941272
TI  - Water affects the stereochemistry and dioxygen reactivity of carboxylate-rich
      diiron(II) models for the diiron centers in dioxygen-dependent non-heme enzymes.
AB  - Carboxylate-bridged high-spin diiron(II) complexes with distinctive electronic
      transitions were prepared by using 4-cyanopyridine (4-NCC(5)H(4)N) ligands to
      shift the charge-transfer bands to the visible region of the absorption spectrum.
      This property facilitated quantitation of water-dependent equilibria in the
      carboxylate-rich diiron(II) complex, [Fe(2)(mu-O(2)CAr(Tol))(4)(4
      NCC(5)H(4)N)(2)] (1), where (-)O(2)CAr(Tol) is 2,6-di-(p-tolyl)benzoate. Addition
      of water to 1 reversibly shifts two of the bridging carboxylate ligands to
      chelating terminal coordination positions, converting the structure from a
      paddlewheel to a windmill geometry and generating [Fe(2)(mu
      O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(4-NCC(5)H(4)N)(2)(H(2)O)(2)] (3). This process
      is temperature dependent in solution, rendering the system thermochromic.
      Quantitative treatment of the temperature-dependent spectroscopic changes over
      the temperature range from 188 to 298 K in CH(2)Cl(2) afforded thermodynamic
      parameters for the interconversion of 1 and 3. Stopped flow kinetic studies
      revealed that water reacts with the diiron(II) center ca. 1000 time faster than
      dioxygen and that the water-containing diiron(II) complex reacts with dioxygen
      ca. 10 times faster than anhydrous analogue 1. Addition of {H(OEt(2))(2)}{B},
      where B(-) is tetrakis(3,5-di(trifluoromethyl)phenyl)borate, to 1 converts it to
      [Fe(2)(mu-O(2)CAr(Tol))(3)(4-NCC(5)H(4)N)(2)](B) (5), which was also structurally
      characterized. Mossbauer spectroscopic investigations of solid samples of 1, 3,
      and 5, in conjunction with several literature values for high-spin iron(II)
      complexes in an oxygen-rich coordination environment, establish a correlation
      between isomer shift, coordination number, and N/O composition. The products of
      oxygenating 1 in CH(2)Cl(2) were identified crystallographically to be [Fe(2)(mu
      OH)(2)(mu-O(2)CAr(Tol))(2)(O(2)CAr(Tol))(2)(4-NCC(5)H(4)N)(2)].2(HO(2)CAr(Tol))
      (6) and [Fe(6)(mu-O)(2)(mu-OH)(4)(mu-O(2)CAr(Tol))(6)(4-NCC(5)H(4)N)(4)Cl(2)]
      (7).

PMID- 15941273
TI  - Asymmetric synthesis of alpha-substituted beta-amino ketones from sulfinimines (N
      sulfinyl imines). synthesis of the indolizidine alkaloid (-)-223A.
AB  - Of the possible four stereoisomers, addition of the lithium enolate of 4
      heptanone to sulfinimines resulted in only the syn- and anti-alpha-substituted
      beta-amino ketones. The formation of the major syn-beta-amino ketone was
      rationalized in terms of addition of the E-enolate to the C-N double bond of the
      sulfinimine via a six-member chelated chairlike transition state. The enolates of
      4-heptanone were generated using LiHMDS in THF where a 1:2.5 E:Z enolate ratio
      was noted. In diethyl ether the E:Z ratio was 15:1 in favor of the E-enolate and
      explained in terms of Ireland's transition state model. Here increased steric
      interactions between the ethyl group and the carbonyl-LiN(TMS)(2) moiety
      destabilize the transition state leading to the Z-enolate in the poorly
      coordinating diethyl ether solvent. This new synthesis of syn-alpha-substituted
      beta-amino ketones was applied to the concise enantioselective total synthesis of
      indolizidine (-)-223A, a 5,6,8-trisubstituted alkaloid isolated from the skin of
      the dendrobatide frog.

PMID- 15941274
TI  - DNA cleavage by copper-ATCUN complexes. Factors influencing cleavage mechanism
      and linearization of dsDNA.
AB  - The reactivity of two [peptide-Cu] complexes ([GGH-Cu](-) and [KGHK-Cu](+))
      toward DNA cleavage has been quantitatively investigated. Neither complex
      promoted hydrolytic cleavage, but efficient oxidative cleavage was observed in
      the presence of a mild reducing agent (ascorbate) and dioxygen. Studies with
      scavengers of ROS confirmed hydrogen peroxide to be an obligatory diffusible
      intermediate. While oxidative cleavage of DNA was observed for Cu(2+)(aq) under
      the conditions used, the kinetics of cleavage and reaction products/pathway were
      distinct from those displayed by [peptide-Cu] complexes. DNA cleavage chemistry
      is mediated by the H(2)O-dependent pathway following C-4'H abstraction from the
      minor groove. Such a cleavage path also provides a ready explanation for the
      linearization reaction promoted by [KGHK-Cu](+). Kinetic activities and reaction
      pathways are compared to published results on other chemical nucleases. Both
      [peptide-Cu] complexes were found to display second-order kinetics, with rate
      constants k(2) approximately 39 and 93 M(-1) s(-1) for [GGH-Cu](-) and [KGHK
      Cu](+), respectively. Neither complex displayed enzyme-like saturation behavior,
      consistent with the relatively low binding affinity and residence time expected
      for association with dsDNA, and the absence of a prereaction complex. However,
      the intrinsic activity of each is superior to other catalyst systems, as
      determined from relative k(2) or k(cat)/K(m) values. Linearization of DNA was
      observed for [KGHK-Cu](+) relative to [GGH-Cu](-), consistent with the increased
      positive charge and longer residency time on dsDNA.

PMID- 15941275
TI  - Gold cluster carbonyls: saturated adsorption of CO on gold cluster cations,
      vibrational spectroscopy, and implications for their structures.
AB  - We report on the interaction of carbon monoxide with cationic gold clusters in
      the gas phase. Successive adsorption of CO molecules on the Au(n)(+) clusters
      proceeds until a cluster size specific saturation coverage is reached. Structural
      information for the bare gold clusters is obtained by comparing the saturation
      stoichiometry with the number of available equivalent sites presented by
      candidate structures of Au(n)(+). Our findings are in agreement with the planar
      structures of the Au(n)(+) cluster cations with n < or = 7 that are suggested by
      ion mobility experiments [Gilb, S.; Weis, P.; Furche, F.; Ahlrichs, R.; Kappes,
      M. M. J. Chem. Phys. 2001, 116, 4094]. By inference we also establish the
      structure of the saturated Au(n)(CO)(m)(+) complexes. In certain cases we find
      evidence suggesting that successive adsorption of CO can distort the metal
      cluster framework. In addition, the vibrational spectra of the Au(n)(CO)(m)(+)
      complexes in both the CO stretching region and in the region of the Au-C stretch
      and the Au-C-O bend are measured using infrared photodepletion spectroscopy. The
      spectra further aid in the structure determination of Au(n)(+), provide
      information on the structure of the Au(n)(+)-CO complexes, and can be compared
      with spectra of CO adsorbates on deposited clusters or surfaces.

PMID- 15941276
TI  - Ring current effects in the active site of medium-chain Acyl-CoA dehydrogenase
      revealed by NMR spectroscopy.
AB  - Medium-chain acyl-CoA dehydrogenase (MCAD) catalyzes the flavin-dependent
      oxidation of fatty acyl-CoAs to the corresponding trans-2-enoyl-CoAs. The
      interaction of hexadienoyl-CoA (HD-CoA), a product analogue, with recombinant pig
      MCAD (pMCAD) has been studied using (13)C NMR and (1)H-(13)C HSQC spectroscopy.
      Upon binding to oxidized pMCAD, the chemical shifts of the C1, C2, and C3 HD
      carbons are shifted upfield by 12.8, 2.1, and 13.8 ppm, respectively. In
      addition, the (1)H chemical shift of the C3-H is also shifted upfield by 1.31 ppm
      while the chemical shift of the C4 HD-CoA carbon is unchanged upon binding. These
      changes in chemical shift are unexpected given the results of previous Raman
      studies which revealed that the C3=C2-C1=O HD enone fragment is polarized upon
      binding to MCAD such that the electron density at the C3 and C1 carbons is
      reduced, not increased (Pellet et al. Biochemistry 2000, 39, 13982-13992). To
      investigate the apparent discrepancy between the NMR and Raman data for HD-CoA
      bound to MCAD, (13)C NMR spectra have been obtained for HD-CoA bound to enoyl-CoA
      hydratase, an enzyme system that has also previously been studied using Raman
      spectroscopy. Significantly, binding to enoyl-CoA hydratase causes the chemical
      shifts of the C1 and C3 HD carbons to move downfield by 4.8 and 5.6 ppm,
      respectively, while the C2 resonance moves upfield by 2.2 ppm, in close agreement
      with the alterations in electron density at these carbons predicted from Raman
      spectroscopy (Bell, A. F.; Wu, J.; Feng, Y.; Tonge, P. J. Biochemistry 2001, 40,
      1725-33). The large increase in shielding experienced by the C1 and C3 HD carbons
      in the HD-CoA/MCAD complex is proposed to arise from the ring current field from
      the isoalloxazine portion of the flavin cofactor. The flavin ring current, which
      is only present when the enzyme is placed in an external magnetic field, also
      explains the differences in (13)C NMR chemical shifts for acetoacetyl-CoA when
      bound as an enolate to MCAD and enoyl-CoA hydratase and is used to rationalize
      the observation that the line widths of the C1 and C3 resonances are narrower
      when the ligands are bound to MCAD than when they are free in the protein
      solution.

PMID- 15941277
TI  - Generalized synthesis of metal phosphide nanorods via thermal decomposition of
      continuously delivered metal-phosphine complexes using a syringe pump.
AB  - We synthesized uniform-sized nanorods of transition metal phosphides from the
      thermal decomposition of continuously delivered metal-phosphine complexes using a
      syringe pump. MnP nanorods with dimensions of 8 nm x 16 nm and 6 nm x 22 nm sized
      were synthesized by the thermal decomposition of Mn-TOP complex, which was
      prepared from the reaction of Mn(2)(CO)(10) and tri-n-octylphosphine (TOP), using
      a syringe pump with constant injection rates of 10 and 20 mL/h, respectively.
      When Co-TOP complex, which was prepared from the reaction of cobalt
      acetylacetonate and TOP, was reacted in a mixture solvent composed of octyl ether
      and hexadecylamine at 300 degrees C using a syringe pump, uniform 2.5 nm x 20 nm
      sized Co(2)P nanorods were generated. When cobaltocene was employed as a
      precursor, uniform Co(2)P nanorods with 5 nm x 15 nm were obtained. When Fe-TOP
      complex was added to trioctylphosphine oxide (TOPO) at 360 degrees C using a
      syringe pump and then allowed to age at 360 degrees C for 30 min, uniform-sized
      FeP nanorods with an average dimension of 12 nm x 500 nm were produced. Nickel
      phosphide (Ni(2)P) nanorods with 4 nm x 8 nm were synthesized successfully by
      thermally decomposing the Ni-TOP complex, which was synthesized by reacting
      acetylacetonate [Ni(acac)(2)] and TOP. We measured the magnetic properties of
      these nanorods, and some of the nanorods exhibited different magnetic
      characteristics compared to the bulk counterparts.

PMID- 15941278
TI  - Biochemical investigation of pikromycin biosynthesis employing native penta- and
      hexaketide chain elongation intermediates.
AB  - The unique ability of the pikromycin (Pik) polyketide synthase to generate 12-
      and 14-membered ring macrolactones presents an opportunity to explore the
      fundamental processes underlying polyketide synthesis, specifically the
      mechanistic details of chain extension, keto group processing, acyl chain
      release, and macrocyclization. We have synthesized the natural pentaketide and
      hexaketide chain elongation intermediates as N-acetyl cysteamine (NAC) thioesters
      and have used them as substrates for in vitro conversions with engineered
      PikAIII+TE and in combination with native PikAIII (module 5) and PikAIV (module
      6) multifunctional proteins. This investigation demonstrates directly the
      remarkable ability of these monomodules to catalyze one or two chain extension
      reactions, keto group processing steps, acyl-ACP release, and cyclization to
      generate 10-deoxymethynolide and narbonolide. The results reveal the enormous
      preference of Pik monomodules for their natural polyketide substrates and provide
      an important comparative analysis with previous studies using unnatural diketide
      NAC thioester substrates.

PMID- 15941279
TI  - On the parity in helical twisting power of Ru(III) 1,3-diketonates of C2 symmetry
      in nematic liquid crystals.
AB  - It is demonstrated that the sign of helical twisting power (HTP) of an
      enantiomeric Ru(III) complex of type [Ru(acac)(2)L] can be switched by choosing L
      from either L(per) or L(para), which is elongated either perpendicular or
      parallel to the C(2) symmetry axis, and four states become available in
      combination with DeltaLambda-chirality of the metal center. Complexes 1-n, in
      which 4,4'-dialkoxylated dibenzoylmethanate ligands are used as L(per), and 2
      having L(para) = 3-(4'-decyloxyphenyl)pentane-2,4-dionate ligand were prepared
      for this purpose. They were optically resolved into the enantiomers by means of a
      clay column chromatography, and their performance as chiral dopants was evaluated
      in nematic liquid crystals including a room-temperature system, N
      methoxybenzylidene-4-n-butylaniline (MBBA), which allowed facile measurements of
      the helical pitch lengths and CD spectra in the induced chiral nematic states.
      The induced CD signals have provided a clear evidence for the helical inversion
      between the two structure types, 1 and 2, of the same chirality. The twisting
      power of these six-coordinate metal complexes and their structure versus twist
      sense correlations are interpreted by the shape model. Intrinsically high HTP of
      Delta-[Ru(acac)(2)L(per)] has also allowed for observation of the pitch band due
      to the selective reflection in the visible wavelength range at the doping level
      of 2 mol % in MBBA.

PMID- 15941280
TI  - Syntheses, structure, and derivatization of potassium complexes of
      penta(organo)[60]fullerene-monoanion, -dianion, and -trianion into hepta- and
      octa(organo)fullerenes.
AB  - Two-electron reduction of penta(organo)[60]fullerenes C(60)Ar(5)H (Ar = Ph and
      biphenyl) by potassium/mercury amalgam afforded potassium complexes of the
      corresponding open-shell radical dianions [K+(thf)n]2[C60Ar5(2-.)]. These
      compounds were characterized by UV-visible-near-IR and electron spin resonance
      spectroscopy in solution. Anaerobic crystallization of
      [K+(thf)n]2[C60(biphenyl)(5)(2-.)] that exists largely as a monomer in solution
      gave black crystals of its dimer [K+(thf)3]4[(biphenyl)5C60-C60(biphenyl)5(4-)],
      in which the two fullerene units are connected by a C-C single bond [1.577(11) A]
      as determined by X-ray diffraction. Three-electron reduction of C60Ar5H with
      metallic potassium gave a black-green trianion [K+(thf)n]3[C60Ar5(3-)]. The
      reaction of the trianion with an alkyl halide RBr (R = PhCH(2) and Ph(2)CH)
      regioselectively afforded a hepta-organofullerene C60Ar5R2H, from which a
      potassium complex [K+(thf)n][C60(biphenyl)5(CH2Ph)(2)(-)] and a palladium complex
      Pd[C60(biphenyl)5(CH2Ph)2](pi-methallyl) as well as octa-organofullerene
      compounds C60(biphenyl)5(CH2Ph)3H2 and Ru[C60(biphenyl)5(C2Ph)3H]Cp were
      synthesized. These compounds possess a dibenzo-fused corannulene pi-electron
      conjugated system and are luminescent.

PMID- 15941281
TI  - Competition at chiral metal surfaces: fundamental aspects of the inversion of
      enantioselectivity in hydrogenations on platinum.
AB  - O-Phenylcinchonidine (PhOCD) is known to efficiently induce inversion of
      enantioselectivity with respect to cinchonidine (CD) in the enantioselective
      hydrogenation of various activated ketones on Pt/Al(2)O(3). To understand the
      origin of the switch of enantioselective properties of the catalyst, the
      adsorption of PhOCD has been studied by in situ ATR-IR spectroscopy, in the
      presence of organic solvent and dissolved hydrogen, i.e., under conditions used
      for catalytic hydrogenation. The adsorption structures and energies of the
      anchoring group of CD and PhOCD were calculated on a Pt 38 cluster, using
      relativistically corrected density functional theory (DFT). Both approaches
      indicate that both modifiers are adsorbed via the quinoline ring and that the
      spatial arrangement of the quinuclidine skeleton is critical for the chiral
      recognition. New molecular level information on the conformation of CD relative
      to PhOCD adsorbed on a surface is extracted from the ATR spectra and supported by
      DFT calculations. The result is a clearer picture of the role played by the
      phenyl group in defining the chiral space created by the modifiers on Pt.
      Moreover, when CD was added to a pre-equilibrated adsorbed layer of PhOCD, a
      chiral adsorbed layer was formed with CD as the dominant modifier, indicating
      that CD adsorbs more strongly than PhOCD. Conversely, when PhOCD was added to
      preadsorbed CD, no significant substitution occurred. The process leading to
      nonlinear effects in heterogeneous asymmetric catalysis has been characterized by
      in situ spectroscopy, and new insight into a heterogeneous catalytic R-S switch
      system is provided.

PMID- 15941282
TI  - Insights into the recognition and association of transmembrane alpha-helices. The
      free energy of alpha-helix dimerization in glycophorin A.
AB  - The free energy of alpha-helix dimerization of the transmembrane (TM) region of
      glycophorin A was estimated from a 125-ns molecular dynamics (MD) simulation in a
      membrane mimetic. The free energy profile was obtained by allowing the TM helical
      segments to diffuse reversibly along the reaction pathway. Partition of the
      potential of mean force into free energy components illuminates the critical
      steps of alpha-helix recognition and association. At large separations, the TM
      segments are pushed together by the solvent, allowing initial, but not
      necessarily native, interhelical interactions to occur. This early recognition
      stage precedes the formation of native contacts, which is accompanied by a tilt
      of the helices, characteristic of the dimeric structure. This step is primarily
      driven by the van der Waals helix-helix interactions. Free energy perturbation
      calculations of the L75A and I76A point mutations reveal a disruption in helix
      helix association due to a loss of favorable dispersion interactions. Additional
      MD simulations of the native TM dimer and of a single alpha-helix confirm that,
      prior to association, individual alpha-helices are independently stable, in
      agreement with the "two-stage" model of integral membrane protein folding.

PMID- 15941283
TI  - Cycloaddition isomerizations of adsorbed 1,3-cyclohexadiene on Si(100)-2x1
      surface: first neighbor interactions.
AB  - The initial and subsequent surface reaction mechanisms of 1,3-cyclohexadiene on
      the Si(100)-2x1 surface were theoretically explored, focusing on the possible
      first-neighbor interactions. Five different initial reaction channels leading to
      nine different surface products were identified, confirming previous experimental
      reports of inter-dimer structures. Among the nine identified products, five of
      these surface products are new species that have not previously been reported.
      Potential energy surface studies reveal that the net reaction barriers within a
      given channel are very small, indicating that the final product distributions
      within that channel are determined by thermodynamics. On the other hand, thermal
      isomerizations between different channels are not expected to occur easily.
      Therefore, the surface product distributions among the five different channels
      are more likely to be determined by kinetics. As a result, understanding the
      relationships among the available reaction channels both kinetically and
      thermodynamically is essential for properly interpreting the experimental
      results. The current study shows that the subsequent surface chemical reactions
      of unsaturated initial surface products are strongly coupled with the first
      neighbor interactions.

PMID- 15941284
TI  - Mercury binding sites in thiol-functionalized mesostructured silica.
AB  - Thiol-functionalized mesostructured silica with anhydrous compositions of
      (SiO(2))(1)(-)(x)()(LSiO(1.5))(x)(), where L is a mercaptopropyl group and x is
      the fraction of functionalized framework silicon centers, are effective trapping
      agents for the removal of mercuric(II) ions from water. In the present work, we
      investigate the mercury-binding mechanism for representative thiol-functionalized
      mesostructures by atomic pair distribution function (PDF) analysis of synchrotron
      X-ray powder diffraction data and by Raman spectroscopy. The mesostructures with
      wormhole framework structures and compositions corresponding to x = 0.30 and 0.50
      were prepared by direct assembly methods in the presence of a structure-directing
      amine porogen. PDF analyses of five mercury-loaded compositions with Hg/S ratios
      of 0.50-1.30 provided evidence for the bridging of thiolate sulfur atoms to two
      metal ion centers and the formation of chain structures on the pore surfaces. We
      find no evidence for Hg-O bonds and can rule out oxygen coordination of the
      mercury at greater than the 10% level. The relative intensities of the PDF peaks
      corresponding to Hg-S and Hg-Hg atomic pairs indicate that the mercury centers
      cluster on the functionalized surfaces by virtue of thiolate bridging, regardless
      of the overall mercury loading. However, the Raman results indicate that the
      complexation of mercury centers by thiolate depends on the mercury loading. At
      low mercury loadings (Hg/S < or = 0.5), the dominant species is an electrically
      neutral complex in which mercury most likely is tetrahedrally coordinated to
      bridging thiolate ligands, as in Hg(SBu(t))(2). At higher loadings (Hg/S 1.0
      1.3), mercury complex cations predominate, as evidenced by the presence of charge
      balancing anions (nitrate) on the surface. This cationic form of bound mercury is
      assigned a linear coordination to two bridging thiolate ligands.

PMID- 15941286
TI  - Electronic coupling in tetraanisylarylenediamine mixed-valence systems: the
      interplay between bridge energy and geometric factors.
AB  - We have investigated three organic mixed-valence systems that possess nearly
      identical inter-redox site distances and differ by the nature of the bridging
      units benzene, naphthalene, and anthracene: the N,N,N',N'-tetra(4-methoxyphenyl)
      1,4-phenylenene-diamine radical cation (1+), the 1,4-bis(N,N-di(4-methoxyphenyl)
      amino)naphthalene radical cation (2+), and the 9,10-bis(N,N-di(4
      methoxyphenyl)amino)anthracene radical cation (3+). The electronic interactions
      in these systems have been studied by means of gas-phase ultraviolet
      photoelectron spectroscopy, vis/NIR spectroscopy, and electronic-structure
      calculations. The experimental and theoretical results concur to indicate that
      the strength of electronic interaction decreases in the following order of
      bridging units: benzene > naphthalene > anthracene. This finding contradicts the
      usual expectation that anthracene is superior to benzene as a driving force for
      electronic communication. We explain these results in terms of a super-exchange
      mechanism and its strong dependence on steric interactions.

PMID- 15941285
TI  - Using mechanistic and computational studies to explain ligand effects in the
      palladium-catalyzed aerobic oxidation of alcohols.
AB  - The experimental and computational mechanistic details of the Pd(OAc)(2)/TEA
      catalyzed aerobic alcohol oxidation system are disclosed. Measurement of various
      kinetic isotope effects and the activation parameters as well as rate law
      derivation support rate-limiting deprotonation of the palladium-coordinated
      alcohol. Rate-limiting deprotonation of the alcohol is contrary to the majority
      of related kinetic studies for Pd-catalyzed aerobic oxidation of alcohols, which
      propose rate-limiting beta-hydride elimination. This difference in the rate
      limiting step is supported by the computational model, which predicts the
      activation energy for deprotonation is 3 kcal/mol higher than the activation
      energy for beta-hydride elimination. The computational features of the similar
      Pd(OAc)(2)/pyridine system were also elucidated. Details of the study illustrate
      that the use of TEA results in an active catalyst that has only one ligand bound
      to the Pd, resulting in a significant lowering of the activation energy for beta
      hydride elimination and, therefore, a catalyst that is active at room
      temperature.

PMID- 15941287
TI  - Polarizing a hydrophobic cavity for the efficient binding of organic guests: the
      case of calix[6]tren, a highly efficient and versatile receptor for neutral or
      cationic species.
AB  - The host-guest properties of calix[6]tren 1 have been evaluated. The receptor is
      based on a calix[6]arene that is covalently capped at the narrow rim by a tren
      unit. As a result, the system presents a concave hydrophobic cavity with, at its
      bottom, a grid-like nitrogenous core. Despite its well-defined cavity and opening
      to the outside at the large rim, 1 did not behave as a good receptor for neutral
      molecules in chloroform. However, it exhibited efficient endo-complexation of
      ammonium guests. By contrast, the per-protonated host, 1.4H(+), behaved as a
      remarkable receptor for small organic molecules. The complexation is driven by a
      strong charge-dipole interaction and hydrogen bonds between the polar guest and
      the tetracationic cap of the calixarene. Finally, coordination of Zn(2+) to the
      tren core led to the asymmetrization of calixarene cavity and to the strong but
      selective endo-binding of neutral ligands. This study emphasizes the efficiency
      of a receptor presenting a concave hydrophobic cavity that is polarized at its
      bottom. The resulting combination of charge-dipole, hydrogen bonding, CH-pi, and
      van der Waals interactions highly stabilizes the supramolecular architectures.
      Also, importantly, the tren cap allows the tuning of the polarization, offering
      either a basic (1), a highly charged and acidic (1.4H(+)), or a coordination
      (1.Zn(2+)) site. As a result, the system proved to be highly versatile, tunable,
      and interconvertible in solution by simple addition of protons, bases, or metal
      ions.

PMID- 15941288
TI  - Enantioselective synthesis of cyclic amides and amines through mo-catalyzed
      asymmetric ring-closing metathesis.
AB  - First, an efficient method for the synthesis of optically enriched N-fused
      bicyclic structures is reported. Through Mo-catalyzed desymmetrization of readily
      available achiral polyene substrates, 5,6-, 5,7-, and 5,8-bicyclic amides can be
      synthesized in up to >98% ee. The effects of catalyst structure, olefin
      substitution, positioning of Lewis basic functional groups and ring size are
      examined and discussed in detail. In the second phase of investigations, a
      catalytic asymmetric method for highly enantioselective (up to 97% ee) synthesis
      of small- and medium-ring unsaturated cyclic amines is reported; optically
      enriched products bear a secondary amine or a readily removable Cbz or acetamide
      unit. Regio- and diastereoselective functionalizations of olefins within the
      optically enriched amine products have been carried out. Both catalytic
      asymmetric methods include transformations that lead to the formation of
      trisubstituted as well as disubstituted cyclic alkenes. The protocols outlined
      herein afford various cyclic amines of high optical purity; such products are not
      easily accessed by alternative protocols and can be used in enantioselective
      total syntheses of biologically active molecules.

PMID- 15941289
TI  - 6-hydroxyquinoline-N-oxides: a new class of "super" photoacids.
AB  - N-Oxidation of hydroxyquinolines leads to a dramatic increase in their excited
      state acidity. Time-resolved and steady-state emission characterization of 6
      hydroxyquinoline-N-oxide and 2-methyl-6-hydroxyquinoline-N-oxide reveals a rich
      but less complex proton-transfer behavior than that of its parent
      hydroxyquinoline. The electronic effect of the oxidized heterocyclic nitrogen
      atom makes the excited state both less basic and more acidic than the parent and
      adds hydroxyquinoline N-oxides to the class of high-acidity excited-state proton
      donors in photochemistry and photobiology. Adiabatic photoinduced proton transfer
      is accompanied by the efficient nonreversible deoxygenation and 1-2 oxygen
      migration.

PMID- 15941290
TI  - Synthesis and characterization of quasi-two-coordinate transition metal
      dithiolates M(SAr*)2 (M = Cr, Mn, Fe, Co, Ni, Zn; Ar* = C6H3-2,6(C6H2-2,4,6
      Pri3)2.
AB  - A sequence of first row transition metal(II) dithiolates M(SAr)(2) (M = Cr(1),
      Mn(2), Fe(3), Co(4), Ni(5) and Zn(6); Ar = C(6)H(3)-2,6-(C(6)H(2)-2,4,6
      Pr(i)(3))(2)) has been synthesized and characterized. Compounds 1-5 were obtained
      by the reaction of two equiv of LiSAr with a metal dihalide, whereas 6 was
      obtained by treatment of ZnMe(2) with 2 equiv of HSAr. They were characterized by
      spectroscopy, magnetic measurements, and X-ray crystallography. The dithiolates
      1, 2, and 4-6 possess linear or nearly linear SMS units with further interactions
      between M and two ipso carbons from C(6)H(2)-2,4,6-Pr(i)(3) rings. The iron
      species 3, however, has a bent geometry, two different Fe-S distances, and an
      interaction between iron and one ipso carbon of a flanking ring. The secondary M
      C interactions vary in strength in the sequence Cr(2+) approximately Fe(2+) >
      Co(2+) approximately Ni(2+) > Mn(2+) approximately Zn(2+) such that the manganese
      and zinc compounds have essentially two coordination but the chromium and iron
      complexes are quasi four and three coordinate, respectively. The geometric
      distortions in the iron species 3 suggested that the structure represents the
      initial stage of a rearrangement into a sandwich structure involving metal-aryl
      ring coordination. The bent structure of 3 probably also precludes the
      observation of free ion magnetism of Fe(2+) recently reported for
      Fe{C(SiMe(3))(3)}(2). DFT calculations on the model compounds M(SPh)(2) (M = Cr
      Ni) support the higher tendency of the iron species to distort its geometry.

PMID- 15941291
TI  - Helical structures of N-alkylated poly(p-benzamide)s.
AB  - Poly(p-benzamide)s 1 bearing a chiral side chain on the nitrogen atom were
      synthesized by chain-growth polycondensation methodology. The polyamides
      exhibited well-defined molecular weights with narrow polydispersities. Solutions
      of the polyamides in several organic solvents (CH(3)CN, CHCl(3), and CH(3)OH)
      showed dispersion type CD signals characteristic of coupled-oscillator and much
      larger as compared with the corresponding monomer. The CD signals were dependent
      on the temperature and molecular weight of the polyamides but independent of the
      solvent, as far as examined. An exciton model analysis of the absorption and CD
      spectra provided a clear-cut picture for the secondary structure of these
      polyamides in solution that the N-alkylated poly(p-benzamide)s possess a right
      handed helical conformation ((P)-helix). In the solid states, the results of X
      ray crystallographic analysis of 4-(methylamino)benzoic acid oligomers
      substantiated that they have a helical conformation with three monomer units per
      turn.

PMID- 15941292
TI  - Controlling the morphology of cross beta-sheet assemblies by rational design.
AB  - Low molecular weight peptidomimetics with simple amphiphilic sequences can help
      to elucidate the structures of cross beta-sheet assemblies, such as amyloid
      fibrils. The peptidomimetics described herein comprise a dibenzofuran template,
      two peptide strands made up of alternating hydrophilic and hydrophobic residues,
      and carboxyl termini, each of which can be varied to probe the structural
      requirements for beta-sheet self-assembly processes. The dibenzofuran template
      positions the strands approximately 10 A apart, allowing corresponding
      hydrophobic side chains in the strands to pack into a collapsed U-shaped
      structure. This conformation is stabilized by hydrophobic interactions, not
      intramolecular hydrogen bonds. Intermolecular stacking of the collapsed
      peptidomimetics, enabled by intermolecular hydrogen bonding and hydrophobic
      interactions, affords 25-27 A wide protofilaments having a cross beta-sheet
      structure. Association of protofilaments, mediated by the dibenzofuran
      substructures and driven by the hydrophobic effect, affords 50-60 A wide
      filaments. These widths can be controlled by changing the length of the peptide
      strands. Further assembly of the filaments into fibrils or ribbons can be
      controlled by modification of the template, C-terminus, and buffer ion
      composition.

PMID- 15941293
TI  - Infrared fingerprint spectroscopy and theoretical studies of potassium ion tagged
      amino acids and peptides in the gas phase.
AB  - Infrared multiple-photon dissociation spectroscopy is effected on the K(+) tagged
      aromatic amino acids tyrosine and phenylalanine, as well as the K(+) tagged
      peptides bradykinin fragment 1-5 and [Leu]-enkephalin. The fingerprint (800-1800
      cm(-1)) infrared spectra of these species are compared to density-functional
      theory (DFT) calculated spectra to determine whether the complex is in the charge
      solvation (CS) or salt bridge (SB) (i.e. zwitterionic) configuration. For the
      aromatic amino acids the CS structure is favored and the tridentate N/O/ring
      structure is found to be the preferred binding geometry for K(+). The
      experimental and theoretical evidence for bradykinin fragment 1-5 tagged with
      K(+) suggests that the SB structure is favored; the calculations indicate a head
      to-tail looped structure stabilized by a salt bridge between the protonated
      guanidine group and the deprotonated C-terminus, which allows K(+) to sit in a
      binding pocket with five C=O electrostatic interactions. For K(+) tagged [Leu]
      enkephalin the spectroscopic evidence is not as clear. While the calculations
      clearly favor a CS structure and the observation of a weak carboxylic acid C=O
      stretching band in the infrared spectrum matches this finding, the prominence of
      a band at 1600 cm(-1) renders the analysis more ambiguous, and hence the presence
      of some salt bridge ions cannot be excluded. Another striking feature in the
      [Leu]-enkephalin spectrum is the high infrared activity of the tyrosine side
      chain modes, which can be clearly identified from comparison to the [Tyr + K](+)
      experimental spectrum, but which is not reproduced by the DFT calculations.

PMID- 15941295
TI  - Environmental fate and effects of Bacillus thuringiensis (Bt) proteins from
      transgenic crops: a review.
AB  - This paper reviews the scientific literature addressing the environmental fate
      and nontarget effects of the Cry protein toxins from Bacillus thuringiensis (Bt),
      specifically resulting from their expression in transgenic crops. Published
      literature on analytical methodologies for the detection and quantification of
      the Cry proteins in environmental matrices is also reviewed, with discussion of
      the adequacy of the techniques for determining the persistence and mobility of
      the Bt proteins. In general, assessment of the nontarget effects of Bt protein
      toxins indicates that there is a low level of hazard to most groups of nontarget
      organisms, although some investigations are of limited ecological relevance. Some
      published reports on the persistence of the proteins in soil show short half
      lives, whereas others show low-level residues lasting for many months.
      Improvements in analytical methods will allow a more complete understanding of
      the fate and significance of Bt proteins in the environment.

PMID- 15941296
TI  - Chemical discrimination of arabica and robusta coffees by Fourier transform Raman
      spectroscopy.
AB  - This article deals with the potential of Fourier transform (FT) Raman
      spectroscopy in discrimination of botanical species of green and roasted coffees.
      There are two species of commercial importance: Coffea arabica (arabica) and
      Coffea canephora (robusta). It is recognized that they differ in their lipid
      fraction, especially in the content of the diterpene kahweol, which is present at
      0.1-0.3% dry matter basis in arabica beans and only in traces (<0.01%) in
      robusta. The visual examination of the Raman spectra of the lipid fraction
      extracted from arabica, robusta and liberica samples shows differences in the mid
      wavenumbers region: arabica spectra have two characteristic scattering bands at
      1567 and 1478 cm(-1). The spectrum of the pure kahweol shows the same bands.
      Principal component analysis is applied to the spectra and reveals clustering
      according to the coffee species. The first principal component (PC1) explains 93%
      of the spectral variation and corresponds to the kahweol concentration. Using the
      PC1 score plot, two groups of arabica can be distinguished as follows: one group
      with high kahweol content and another group with low kahweol content. The first
      group includes samples coming from Kenya and Jamaica; the second group includes
      samples from Australia. The main difference between these coffees is that those
      from Kenya and Jamaica are well-known for growing at a high altitude whereas
      those ones from Australia are grown at a low altitude. To our knowledge, the
      application of Raman spectroscopy has never been used in coffee analysis.

PMID- 15941297
TI  - Extraction of isoflavone malonylglucosides from Trifolium pratense L.
AB  - Extraction of isoflavone malonylglucosides from red clover (Trifolium pratense
      L.) is a complicated procedure. This is due to the relatively unstable character
      of the thermolabile glucoside malonates as well as by action of native beta
      glucosidases, resulting in a rapid degradation of malonylated glucosides into
      their corresponding aglucones. In this study, Tris was identified as a suitable
      beta-glucosidase inhibitor in red clover extracts, optimized at 350 mM Tris in
      80% ethanol at pH 7.2. Extraction of fresh red clover leaves using Tris increased
      the concentration of malonate conjugated isoflavones approximately 13 to 24 times
      as opposed to extraction without Tris. A comparison of isoflavone profiles
      obtained after extraction with and without Tris of different plant organs of red
      clover and several species within the family Fabaceae suggests that the amount
      and/or activity of the degenerative beta-glucosidase enzymes vary for the
      different plant parts of red clover and among the species studied. Therefore, the
      use of standard extraction methods may well result in overestimation of the
      concentration of aglucones and consequently underestimation of the
      malonylglucoside isoflavones concentration depending on the plant species and
      plant part studied.

PMID- 15941298
TI  - Separation and identification of phenolic compounds in olive oil by coupling high
      performance liquid chromatography with postcolumn solid-phase extraction to
      nuclear magnetic resonance spectroscopy (LC-SPE-NMR).
AB  - This study reports the first application of the hyphenated LC-SPE-NMR technique
      using postcolumn solid-phase extraction to the direct analysis of phenolic
      compounds in the polar part of olive oil. Apart from the identification and
      structure elucidation of simple phenols (hydroxytyrosol, tyrosol, vanillic acid,
      vanillin, p-coumaric acid, hydroxytyrosol, and tyrosol acetates), lignans
      (pinoresinol and 1-acetoxypinoresinol), flavonoids (apigenin and luteolin), and a
      large number of secoiridoid derivatives, this technique enables the
      identification of several new phenolic components, which had not been reported
      previously as constituents in the polar part of olive oil.

PMID- 15941299
TI  - The determination of semicarbazide (N-aminourea) in commercial bread products by
      liquid chromatography-mass spectrometry.
AB  - Recently, semicarbazide has been found in food in jars sealed with cap liners
      that were manufactured using azodicarbonamide as a blowing agent. These reports
      raised the concern that the use of azodicarbonamide-an approved dough conditioner
      may result in semicarbazide residues in bread. To answer this question, a method
      based upon the previously reported liquid chromatography/tandem mass spectrometry
      determination of the semicarbazone of o-nitrobenzaldehyde was utilized. The
      method adopted for this work includes an extensive cleanup and reaction with o
      nitrobenzaldehyde at pH 3.5, rather than with the widely used 0.1 M HCl, to form
      the semicarbazone derivative. A stable isotope dilution assay was used to
      determine the free semicarbazide present in the bread products. Levels of
      semicarbazide ranged from 10 to 1200 ppb in commercial bread products with
      azodicarbonamide listed among their ingredients.

PMID- 15941300
TI  - Determination of total N-nitroso compounds by chemical denitrosation using CuCl.
AB  - A method for the determination of total N-nitroso compounds (NOC) by chemical
      denitrosation and subsequent chemiluminescence detection of evolved NO is
      described. Denitrosation was accomplished with CuCl in HCl at 70 degrees C. The
      detection limit for N-nitrosoproline (NPRO) was 1 pmol. NO formation from NPRO
      was linear (R(2) = 0.999) from 4 pmol to 2 nmol. Among the possible interfering
      compounds tested, only S-nitroso compounds contribute any significant
      interference. This method had several advantages over other similar methods: (1)
      A commercially available one-piece reaction vessel and a NO analyzer with
      software were used. (2) NO release occurred rapidly and was easily measured and
      quantified. (3) Compared to HBr or HI, CuCl was more convenient to work with and
      safe. (4) CuCl was suitable for samples in aqueous and most organic solvents. The
      application of this method to food, personal care products, and human body fluids
      demonstrates its utility.

PMID- 15941301
TI  - Triacylglycerol structure and composition of hydrogenated soybean oil margarine
      and shortening basestocks.
AB  - The composition and structures of triacylglycerols (TAG) in a commercially
      prepared hydrogenated soybean oil margarine basestock [iodine value (IV) 65,
      39.7% trans fatty acids] were determined by high-performance liquid
      chromatography (HPLC) in tandem with atmospheric pressure chemical ionization
      (APCI) mass spectrometry (MS). The basestock was separated by preparative HPLC
      into four fractions. Fractions 1 and 4, constituting approximately 8% of the
      total, were shown to consist of LOO, PLO, and LLS and OSS and PSS, respectively
      (where L = linoleic, O = oleic, S = stearic, and P = palmitic). APCI will not
      distinguish between O, oleic cis C18:1, and E, elaidic trans C18:1. Thus, O and E
      may be used interchangeably in discussion of TAG isomer structures. Fraction 2
      consisted of OOO and POO. Fraction 3 consisted of OOO, POO, OOS, and POS. About
      80% of the total triglycerides consisted of OOO, POO, and OOS. The trans fatty
      acid content of the fractions was determined, and the results showed that 92% of
      the total trans content was found in fractions 2 and 3. A shortening basestock
      (IV 81.7, 31.8% trans fatty acids) was partially characterized.

PMID- 15941302
TI  - Rapid multimineral determination in infant cereal matrices using wavelength
      dispersive X-ray fluorescence.
AB  - A rapid and simple method for the determination of a series of macroelements
      (sodium, magnesium, phosphorus, chlorine, potassium, and calcium) and trace
      elements (manganese, iron, and zinc) by wavelength dispersive X-ray fluorescence
      has been developed and validated for infant cereal matrices. Reference values
      were obtained by inductively coupled plasma optical emission spectroscopy and by
      potentiometry. The 88 investigated samples were commercially available products.
      Pellets of 4 g were prepared under 10 tonnes of pressure. For each sample, 3
      pellets were prepared and analyzed. Limits of quantification and repeatabilities
      were evaluated. Calibrations were established with 43 samples, and method
      validation was made using a second set of 45 samples. An evaluation of this
      alternative method was done by comparison with data obtained from the reference
      methods. The results show the good performances of the alternative method to
      routine infant cereals analysis.

PMID- 15941303
TI  - Analysis of hop-derived terpenoids in beer and evaluation of their behavior using
      the stir bar-sorptive extraction method with GC-MS.
AB  - Hop aroma components, which mainly comprise terpenoids, contribute to the
      character of beers. However, pretreatments are necessary before analyzing these
      components because of their trace levels and complicated matrixes. Here, the stir
      bar-sorptive extraction (SBSE) method was used to detect and quantify many
      terpenoids simultaneously from small samples. This simple technique showed low
      coefficients of variation, high accuracy, and low detection limits. An
      investigation of the behavior of terpenoids identified two distinct patterns of
      decreasing concentration during wort boiling. The first, which was seen in
      myrcene and linalool, involved a rapid decrease that was best fitted by a
      quadratic curve. The second, which was observed in beta-eudesmol, humulene,
      humulene epoxide I, beta-farnesene, caryophyllene, and geraniol, involved a
      gentle linear decrease. Conversely, the concentration of beta-damascenone
      increased after boiling. As the aroma composition depended on the hop variety, we
      also examined the relationship between terpenoid content and sensory analysis in
      beer.

PMID- 15941304
TI  - Improved malonaldehyde assay using headspace solid-phase microextraction and its
      application to the measurement of the antioxidant activity of phytochemicals.
AB  - A modified malonaldehyde (MA) assay for antioxidant activity, which involves
      derivatization and headspace solid-phase microextraction (HS-SPME) was developed
      and validated. The recovery of MA as 1-methylpyrazole (product of MA and N
      methylhydrazine) from a headspace of an aqueous solution containing MA, buffer,
      surfactant, and cod liver oil using HS-SPME with a PDMS/DVB fiber was 91.3 +/-
      3.38%. MA was analyzed by a gas chromatograph with a nitrogen-phosphorus
      detector, and its detection limit was 0.0103 nmol/mL. The antioxidant activities
      of natural compounds were determined as the percentage inhibition of MA formed
      from cod liver oil oxidized by Fenton's reagents in the above aqueous solution.
      Sesamol inhibited MA formation most (86.1%), followed by eugenol (84.4%),
      capsaicin (80.7%), ethylvanillin (45.3%), and vanillin (31.6%) at a level of 50
      microg/mL. This method did not require any organic solvents and is a simple,
      fast, and a highly sensitive method for MA determination.

PMID- 15941305
TI  - Inositol phosphate profiling of fermented cowpeas by 1H NMR spectroscopy.
AB  - The inositol phosphate content of naturally fermented cowpeas (Vigna sinensis
      var. Carilla) was studied using ion-pair HPLC and 1H NMR spectroscopy. The
      fermented flour was extracted with 0.5 M HCl, and the extract was purified and
      fractionated by ion-exchange chromatography. 1H NMR allowed for the
      identification of two monophosphates [Ins(1 or 3)P1 and Ins(4 or 6)P1], one
      inositol diphosphate [Ins(1,4)P2], three inositol triphosphates [Ins(1,2,6)P3,
      Ins(1,5,6)P3, and Ins(1,4,5)P3], one inositol tetraphosphate [Ins(1,3,4,5)P4],
      and one inositol pentaphosphate [Ins(1,2,3,5,6)P5]. Some of these isomers
      [Ins(1,4,5)P3 and Ins(1,3,4,5)P4] are considered to play important biological
      roles in intracellular signaling.

PMID- 15941306
TI  - New dammarane-type saponins from the galls of Sapindus mukorossi.
AB  - Five new dammarane-type saponins, 3beta,7beta,20(S),22-tetrahydroxydammar-24-ene
      3-O-alpha-l-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside,
      3beta,7beta,20(S),22,23-pentahydroxydammar-24-ene-3-O-alpha-l-rhamnopyranosyl-(1-
      >2)-beta-D-glucopyranoside, 3beta,7beta,20(S),22,25-pentahydroxydammar-23-ene-3-O
      alpha-l-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside, 25-methoxy
      3beta,7beta,20(S),22-tetrahydroxydammar-23-ene-3-O-alpha-l-rhamnopyranosyl-(1-
      >2)-beta-D-glucopyranoside, and 25-methoxy-3beta,7beta,20(R)-trihydroxydammar-23
      ene-3-O-alpha-l-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside, named
      sapinmusaponins A (1), B (2), C (3), D (4), and E (5), respectively, together
      with three known phenylpropanoid glycosides (6-8), were isolated from the galls
      of Sapindus mukorossi. The structures of these saponins were elucidated on the
      basis of spectroscopic analyses and chemical methods. Preliminary bioassay data
      revealed that saponins 1 and 3-5 showed moderate cytotoxic activity (ED50
      approximately 9-18 microg/mL) against human tumor cell lines (Hepa59T/VGH, NCI,
      HeLa, and Med) and that 1-5 were inactive in vitro against HIV replication in H9
      lymphocytes.

PMID- 15941307
TI  - Procyanidin fractions from pine (Pinus pinaster) bark: radical scavenging power
      in solution, antioxidant activity in emulsion, and antiproliferative effect in
      melanoma cells.
AB  - Pine (Pinus pinaster) bark is a rich source of procyanidin oligomers. From a
      total polyphenolic extract, we have generated fractions of different procyanidin
      composition. The mixtures, devoid of gallate esters, were active as free radical
      scavengers against ABTS(*+), DPPH, and HNTTM. Pine bark fractions were tested for
      antioxidant activity in solution (hydrogen donation and electron transfer) and
      emulsion (inhibition of lipid peroxidation) and compared with their galloylated
      counterparts from grape origin. While galloylation clearly influenced the free
      radical scavenging efficiency in solution, it did not seem to play a determinant
      role in protection against lipid peroxidation in emulsion. The fractions were
      very mild inhibitors of cell proliferation. Because gallate esters appear to
      interfere with crucial cell functions, gallate free pine procyanidins may be the
      innocuous chemopreventative agents of choice for many applications in food and
      skin protection.

PMID- 15941308
TI  - Quantitation of carnosine in humans plasma after dietary consumption of beef.
AB  - Carnosine (beta-alanyl-L-histidine) is a dipeptide found in the muscle foods that
      has been postulated to be a bioactive food component. The objective of this
      research was to determine the concentration of carnosine in human plasma after
      ingestion of beef. Nine males and nine females were recruited for the study. Food
      devoid of meat products was given to the subjects so that they did not consume
      carnosine for 48 h prior to the test. Subjects fasted for 12 h and then had blood
      withdrawn prior to a meal containing 200 g of ground beef. Additional blood
      samples were collected over the following 24 h and carnosine concentrations were
      determined by HPLC. The cooked ground beef used in the study contained 52% water,
      24% protein, 22% fat, and 124 mg of carnosine/100 g of beef. No plasma carnosine
      was detected in subjects before the consumption of the beef. Carnosine was
      detected in plasma 15 min after beef consumption. Plasma carnosine concentrations
      continued to increase with a maximum (32.7 mg of carnosine/L of plasma) being
      recorded 2.5 h after consumption. Carnosine concentrations then decreased until
      no carnosine could be detected at 5.5 h postconsumption. These results indicate
      that dietary carnosine is absorbed into human plasma after the consumption of
      beef. Since carnosine has several potential health benefits, evidence of its
      bioavailability suggests that it could be a bioactive food component.

PMID- 15941309
TI  - Pharmacokinetic study of caffeic and rosmarinic acids in rats after oral
      administration.
AB  - p-Coumaric and ferulic acid are actively taken up by monocarboxylic acid
      transporter (MCT), whereas gallic acid, caffeic acid (CA), and rosmarinic acid
      (RA) are absorbed by paracellular diffusion in human intestinal Caco-2 cells,
      although CA has low affinity for MCT. We previously demonstrated that p-coumaric
      acid has a much higher absorption efficiency than gallic acid in rats, owing to
      the MCT-mediated absorption of p-coumaric acid in vivo (J. Agric. Food Chem.
      2004, 52, 2527-2532). Here, absorption of orally administered CA and RA in rats
      has been studied to investigate their intestinal absorption characteristics and
      pharmacokinetics in vivo and to compare the results with those of p-coumaric and
      gallic acids obtained under identical conditions. Rats were given 100 micromol/kg
      body weight of CA and RA, and blood was collected from the portal vein and
      abdominal artery after administration. CA, RA, and their metabolites were
      quantified by a coulometric detection method using HPLC-ECD. The serum
      concentration of intact CA and RA in the portal vein peaked at 10 min after
      administration, with a C(max) of 11.24 micromol/L for CA and 1.36 micromol/L for
      RA. The area under the curve (AUC) for intact CA and RA in the portal vein was
      calculated from the serum concentration-time profile to be 585.0 and 60.4
      micromol min L-1, respectively. The absorption efficiency of CA was about 9.7
      fold higher than that of RA. Overall, the absorption efficiency of these
      compounds in vivo increases in the order: gallic acid = RA < CA < p-coumaric
      acid, which is in good agreement with results obtained in Caco-2 cells in vitro.

PMID- 15941310
TI  - Variation of chemical composition of the lipophilic extracts from yellow birch
      (Betula alleghaniensis) foliage.
AB  - The occurrence of biologically active compounds identified for the first time in
      the lipophilic extracts of yellow birch (Betula alleghaniensis Britt.) foliage
      led to the quantification of the seasonal variation of their concentrations.
      Yellow birch foliage was collected from late June until late September 2003 in
      two different regions of Quebec. The extraction yields using hexane as a solvent
      were determined, and the extracts were analyzed by GC-MS to identify their
      molecular composition. In terms of both extraction yields and the concentration
      of the targeted molecules present in the extracts, mid-September has been
      determined as the best time to collect foliage samples. A total of 14
      constituents were identified in these extracts. This is the first report of the
      presence of all of these constituents in yellow birch foliage and of some of them
      in the genus Betula. The most important compounds identified in yellow birch
      foliage extracts are triterpene squalene and aliphatic hydrocarbon tetracosan,
      aliphatic alcohol phytol, fatty acids hexadecanoic and octadecanoic, pentacyclic
      triterpenes alpha- and beta-amyrin, and phytosterol stigmast-5-en-3-ol.

PMID- 15941311
TI  - Antioxidant activity of the flavonoid hesperidin in chemical and biological
      systems.
AB  - The antioxidant hesperidin, a major flavonoid in sweet orange and lemon, was
      evaluated using chemical and biological systems. The chemical assay evaluates the
      hesperidin capacity to sequester 1,1-diphenyl-2-picrylhydrazyl (DPPH*).
      Biological studies were done using the eukaryotic cells of superoxide-dismutase
      proficient and deficient strains of Saccharomyces cerevisiae treated with
      hesperidin and the stressing agents hydrogen peroxide or paraquat
      (methylviologen; 1,1'-dimethyl-4,4'-bipyridinium dichloride). Hesperidin was able
      to reduce significantly the level of the free radical DPPH* with similar efficacy
      of trolox (positive control). When the yeast cells were exposed to the flavonoid
      hesperidin before the stressing agents, there was a significant increase in the
      survival of all strains. Paraquat induced higher catalase and superoxide
      dismutase than did hydrogen peroxide, which only increased catalase activity.
      Previous addition of hesperidin to these treatments was able to reduce
      significantly both enzymatic levels. These observations clearly demonstrate that
      hesperidin provides strong cellular antioxidant protection against the damaging
      effects induced by paraquat and peroxide hydrogen.

PMID- 15941312
TI  - In vitro activity of the essential oil of Cinnamomum zeylanicum and eugenol in
      peroxynitrite-induced oxidative processes.
AB  - The essential oil obtained from the bark of Cinnamomum zeylanicum Blume
      (Lauraceae) and three of its main components, eugenol, (E)-cinnamaldehyde, and
      linalool (representing 82.5% of the total composition), were tested in two in
      vitro models of peroxynitrite-induced nitration and lipid peroxidation. The
      essential oil and eugenol showed very powerful activities, decreasing 3
      nitrotyrosine formation with IC50 values of 18.4 microg/mL and 46.7 microM,
      respectively (reference compound, ascorbic acid, 71.3 microg/mL and 405.0 microM)
      and also inhibiting the peroxynitrite-induced lipid peroxidation showing an IC50
      of 2.0 microg/mL and 13.1 microM, respectively, against 59.0 microg/mL (235.5
      microM) of the reference compound Trolox. On the contrary, (E)-cinnamaldehyde and
      linalool were completely inactive.

PMID- 15941313
TI  - Induction of phenolsulfotransferase expression by phenolic acids in human
      hepatoma HepG2 cells.
AB  - Phenolic acids are antioxidant phenolic compounds, widespread in plant foods,
      which contribute significant biological and pharmacological properties; some have
      demonstrated a remarkable ability to alter sulfate conjugation. However, the
      modulation mechanisms of antioxidant phenolic acids on phenolsulfotransferase
      activity have not yet been described. In the present study, the human hepatoma
      cell line, HepG2, was used as a model to investigate the effect of antioxidant
      phenolic acids on enzymatic activity and expression of one of the major phase II
      sulfate conjugation enzymes, P-form phenolsulfotransferase (PST-P). The results
      showed that gallic acid, gentisic acid, p-hydroxybenzoic acid, and p-coumaric
      acid increased PST-P activity, in a dose-dependent manner. A maximum of 4- and 5
      fold induction of PST-P activity was observed for both gallic acid and gentisic
      acid; however, they showed an adverse effect on cell growth at higher
      concentrations. A 2- or 2.5-fold increase of PST-P activity was found with either
      p-coumaric or p-hydroxybenzoic acid treatment, whereas no significant effect was
      found for ferulic acid treatment. PST-P induction, by gallic acid, was further
      confirmed, using reverse transcription PCR and Western blotting techniques to
      measure mRNA expression and protein translation. A significant correlation (r =
      0.74, p < 0.01) between the expressions of PST-P mRNA and the corresponding PST-P
      activity was observed. Thus, gallic acid increased PST-P protein expression in
      HepG2 cells, in a dose- and time-dependent manner. The results demonstrated that
      certain antioxidant phenolic acids could induce PST-P activity in HepG2 cells, by
      promoting PST-P mRNA and protein expression, suggesting a novel mechanism by
      which phenolic acids may be implicated in phase II sulfate conjugation.

PMID- 15941314
TI  - Biological activity and chemical composition of the essential oil from Jamaican
      Hyptis verticillata Jacq.
AB  - The chemical composition of the essential oil obtained by hydrodistillation from
      the aerial parts of Hyptis verticillata Jacq. was elucidated by a combination of
      GC and GC-MS analyses. The oil was dominated by the sesquiterpenoids cadina
      4,10(15)-dien-3-one (15.1%) (1) and aromadendr-1(10)-en-9-one (squamulosone)
      (30.7%) (2). The oil exhibited chemosterilant activities against the cattle tick,
      Boophilus microplus Canest., and toxic action against adult Cylas formicarius
      elegantulus Summer, the most destructive pest of sweet potato (Ipomoea species).

PMID- 15941315
TI  - Effect of soybean lipoxygenase on volatile generation and inhibition of
      Aspergillus flavus mycelial growth.
AB  - Volatiles generated from lipoxygenase (LOX) normal and LOX deficient soybean
      (Glycine max) varieties with and without added lipase inhibited Aspergillus
      flavus mycelial growth and aflatoxin production. Soybean volatiles were analyzed
      using a solid phase microextraction (SPME) method combined with gas
      chromatography-mass spectrometry (GC-MS). Twenty-one compounds, including 11
      aldehydes, three alcohols, four ketones, one furan, one alkane, and one alkene
      were detected in the LOX normal soybean line. However, only nine volatile
      compounds were observed in the LOX deficient soybean variety. The antifungal
      aldehydes hexanal and (E)-2-hexenal were observed in both LOX normal and LOX
      deficient lines and were detected at significantly higher amounts in soybean
      homogenate with added lipase. These aldehydes may be formed through alternate
      pathways, other than the LOX pathway, and may account for the inhibition of A.
      flavus growth observed. Other volatiles detected, particularly the ketones and
      alcohols, may contribute to the antifungal activity observed in both LOX normal
      and LOX deficient soybean lines. These results suggest that other factors, other
      than LOX activity, may better explain why soybeans are generally not as severely
      affected by A. flavus and aflatoxin contamination as other oilseed crops.

PMID- 15941316
TI  - Sicklepod (Senna obtusifolia) seed processing and potential utilization.
AB  - Sicklepod (Senna obtusifolia) is a leguminous plant that infests soybean fields
      in the southeastern United States. Its seeds contain a variety of toxic, highly
      colored compounds, mainly anthraquinones together with a small amount of fat.
      These compounds contaminate and lower the quality of soybean oil when
      inadequately cleaned soybean seed from this area is processed. The sorting of
      sicklepod seed from a soybean harvest is an additional economic burden on the
      farmer beyond the cost of proper disposal of the weed seed to avoid worsening
      field infestation. Fortunately, sicklepod seed also contains substantial amounts
      of carbohydrates and proteins. These edible components when freed from
      anthraquinones have a market in pet food as well as potential in human foods
      because of the high galactomannan ratio of the polysaccharides. Sicklepod seed
      was dehulled, and the ground endosperm was defatted, followed by sequential
      solvent extraction of the defatted seed meal to isolate the anthraquinones,
      carbohydrates, and protein components into their respective classes. Each class
      of isolate was spectroscopically identified.

PMID- 15941317
TI  - Encapsulation of essential oils in zein nanospherical particles.
AB  - Three essential oils, oregano, red thyme, and cassia (100% pure oil), were
      encapsulated by phase separation into zein nanospheres. Topographical images
      indicated that the powders were made up of irregularly shaped particles (
      approximately 50 mum) containing close-packed nanospheres. Approximately 31% of
      the oregano encapsulated particles had mean diameters greater than 100 nm
      compared to 19% for the zein alone particles. In vitro digestion of zein
      particles with pepsin at a concentration ratio of 10:1 was complete after 52 h in
      phosphate-citrate buffer, pH 3.5, at 37 degrees C by spectroscopic analysis.
      Nonenzymatic, aqueous in vitro release of essential oils from encapsulated zein
      particles was carried out in phosphate buffered saline at pH 7.4 and 37 degrees
      C. Release occurred at varying rates over 20 h probably from different locations
      within the closely packed nanospheres of different sizes. Gel electrophoresis SDS
      PAGE of zein incubated with freeze-dried swine manure solids at 37 degrees C
      indicated that preformed microbial enzymes capable of digesting zein within
      minutes were present in the manure. Except for differences in size of
      nanospheres, no structural differences were resolved by several microscopic
      methods, suggesting that the oil and proteins phases were blended during phase
      separation.

PMID- 15941318
TI  - Cloning and molecular analysis of the regulatory factor HlMyb1 in hop (Humulus
      lupulus L.) and the potential of hop to produce bioactive prenylated flavonoids.
AB  - The concentrations of prenylated chalcones and bitter acids were analyzed in
      Czech hop varieties. The highest levels of (xanthohumol + desmethylxanthohumol)
      (0.97%, m/m) and of total bitter acids (17.19%, m/m) were observed for cv. Agnus.
      The concentration ratios of bitter acids to prenylated chalcones varied depending
      on the genotype, thereby suggesting genetic determination by different set(s) of
      structural and regulatory genes. Promoter elements of the chs_H1 gene encoding a
      "true"chalcone synthase, a candidate gene to co-determine the biosynthesis of
      prenylated chalcones, were analyzed, and several boxes for cis-regulatory
      elements including Myb transcription factors were discovered. A cDNA library was
      established from glandular tissue-enriched cones of cv. Osvald's clone 72 and
      used to screen for Myb regulatory elements. The cDNA of the first Myb regulatory
      factor from hop, called HlMyb1, was cloned and analyzed. The HlMyb1 open reading
      frame encodes 272 amino acids (29.8 kDa), and the protein showed highest homology
      to the light-regulated factor AtMyb68 from Arabidopsis thaliana within the Myb
      domain, whereas there was no significant homology with known MYB proteins outside
      this domain. Unlike AtMyb68, which is expressed in mature leaves, HlMyb1 is
      strongly expressed in hop inflorescences and could participate in the regulation
      of developmental processes involved in the production of hop cones and bioactive
      secondary metabolites.

PMID- 15941319
TI  - Efficient system of artificial oil bodies for functional expression and
      purification of recombinant nattokinase in Escherichia coli.
AB  - Nattokinase, a serine protease, and pronattokinase, when expressed in Escherichia
      coli, formed insoluble aggregates without enzymatic activity. For functional
      expression and purification, nattokinase or pronattokinase was first
      overexpressed in E. coli as an insoluble recombinant protein linked to the C
      terminus of oleosin, a structural protein of seed oil bodies, by an intein
      fragment. Artificial oil bodies were reconstituted with triacylglycerol,
      phospholipid, and the insoluble recombinant protein thus formed. Soluble
      nattokinase was subsequently released through self-splicing of intein induced by
      temperature alteration, with the remaining oleosin-intein residing in oil bodies
      and the leading propeptide of pronattokinase, when present, spontaneously cleaved
      in the process. Active nattokinase with fibrinolytic activity was harvested by
      concentrating the supernatant. Nattokinase released from oleosin-intein
      pronattokinase exhibited 5 times higher activity than that released from oleosin
      intein-nattokinase, although the production yields were similar in both cases.
      Furthermore, active nattokinase could be harvested in the same system by fusing
      pronattokinase to the N terminus of oleosin via a different intein linker, with
      self-splicing induced by 1,4-dithiothreitol. These results have shown a great
      potential of this system for bacterial expression and purification of functional
      recombinant proteins.

PMID- 15941320
TI  - Detection of proteins related to starch synthase activity in the developing
      mungbean (Vigna radiata L.).
AB  - Proteins associated with starch synthase (SS) activities were identified in
      immature mungbeans (Vigna radiata L. cv KPS1). Seed soluble extract was separated
      by native-PAGE and subjected to in situ activity staining. The gel zymogram
      located starch-enzyme complex bands. The soluble extract was also partitioned by
      preparative-IEF and screened for SS activity using radioactive assay. IEF
      fractions eluted within pH 4-6 revealed enriched SS activity of 145-fold.
      Parallel comparison of the protein profiles among the activity stained enzyme
      complex and the active isoelectric focused fractions on SDS-PAGE depicted three
      SS-activity-related proteins with molecular size of 32, 53, and 85 kDa. The 85
      kDa protein, however, was identified to be methionine synthase by MALDI-TOF
      analysis and should be a protein physically associated with the active SS.
      Polyclonal antibodies raised from eluted native enzyme complex neutralized up to
      90% activity and antigenically recognize the other 53 and 32 kDa proteins on
      Western blot. Antibodies raised from the two individual denatured proteins were
      able to neutralize SS activities near 60% separately, indicating that the 53 kDa
      and 32 proteins associated with SS activity are potentially involved in starch
      biosynthesis during mungbean seed development.

PMID- 15941321
TI  - Correlation of acrylamide generation in thermally processed model systems of
      asparagine and glucose with color formation, amounts of pyrazines formed, and
      antioxidative properties of extracts.
AB  - The relations between the formation of acrylamide and color, pyrazines, or
      antioxidants in an asparagine/d-glucose browning model system under various
      conditions were investigated. The highest level of acrylamide was produced in the
      asparagine/glucose (1:3) system heated at 170 degrees C for 30 min (2629 microg/g
      asparagine). Color intensity increased with temperature and heating time. The
      formation of pyrazines increased steadily with an increase of temperature (140
      170 degrees C) and heating time (15-60 min). Antioxidant formation varied among
      the samples heated under different conditions. A clear correlation between
      formation of acrylamide and browning color was obtained. The formation of
      acrylamide was linearly correlated with the formation of total pyrazines during
      the initial stages of the Maillard reaction. No obvious correlation between
      formation of acrylamide and antioxidants was observed. However, excess amounts of
      asparagine increased the formation of antioxidants, whereas excess amounts of
      glucose reduced its formation.

PMID- 15941322
TI  - Thermal degradation products formed from carotenoids during a heat-induced
      degradation process of paprika oleoresins (Capsicum annuum L.).
AB  - The high-temperature treatment of paprika oleoresins (Capsicum annuum L.)
      modified the carotenoid profile, yielding several degradation products, which
      were analyzed by HPLC-APCI-MS. From the initial MS data, compounds were grouped
      in two sets. Set 1 grouped compounds with m/z 495, and set 2 included compounds
      with m/z 479, in both cases for the protonated molecular mass. Two compounds of
      the first set were tentatively identified as 9,10,11,12,13,14,19,20-octanor
      capsorubin (compound II) and 9,10,11,12,13,14,19,20-octanor-5,6-epoxide
      capsanthin (compound IV), after isolation by semipreparative HPLC and analysis by
      EI-MS. Compounds VII, VIII, and IX from set 2 were assigned as
      9,10,11,12,13,14,19,20-octanor-capsanthin and isomers, respectively. As these
      compounds were the major products formed in the thermal process, it was possible
      to apply derivatization techniques (hydrogenation and silylation) to analyze them
      by EI-MS, before and after chemical derivatization. Taking into account
      structures of the degradation products, the cyclization of polyolefins could be
      considered as the general reaction pathway in thermally induced reactions,
      yielding in the present study xylene as byproduct and the corresponding nor
      carotenoids.

PMID- 15941323
TI  - Accumulation of all-trans-beta-carotene and its 9-cis and 13-cis stereoisomers
      during postharvest ripening of nine Thai mango cultivars.
AB  - Accumulation of beta-carotene during postharvest ripening of nine Thai mango
      cultivars was assessed after verifying extraction and high-performance liquid
      chromatographic quantification of the beta-carotene stereoisomers for this sample
      matrix. No relevant trans-cis isomerization was induced by the analytical
      procedure. The vitamin A potential of mangoes was evaluated at different ripening
      stages unequivocally defined by a ripening index (RPIWB). Being rather stable
      throughout postharvest ripening, the cultivar-specific proportion of cis-beta
      carotene isomers ranged from 14 to 40% of the total beta-carotene content.
      Subjected to the same postharvest ripening conditions, only the cultivars Kaew,
      Maha Chanok, Chok Anan, and Nam Dokmai #4 developed a bright yellow-orange
      mesocarp coloration at their fully ripe stage (RPIWB = 1.5-1.8, sugar-acid ratio
      approximately 50), resulting in total beta-carotene contents of 6544-11249
      microg/100 g mesocarp dry weight (DW) and vitamin A values of 892-1573 retinol
      equivalents (RE)/100 g DW. Contrarily, poor-colored cultivars Mon Duen Gao, Rad,
      Kiew Sawoei, Okrong Kiew, and Okrong Thong reached total beta-carotene contents
      of 1019-2195 microg/100 g DW and vitamin A values of 136-298 RE/100 g DW at
      comparable sugar-acid ratios. Exponential development of mesocarp color (hue
      angle, H degrees ) and all-trans-beta-carotene levels, respectively, with RPIWB
      was described for each cultivar, allowing good prediction of mesocarp color and
      vitamin A value at consumption ripeness.

PMID- 15941324
TI  - Phenolic profiles of raw apricots, pumpkins, and their purees in the evaluation
      of apricot nectar and jam authenticity.
AB  - The possibility of proving the undeclared addition of pumpkin puree in apricot
      nectars and jams has been investigated by using the phenol compound fingerprint
      and sensory evaluation. The cheaper pumpkin admixtures in apricot nectars and
      jams could not be detected by the sensory evaluation, particularly if present in
      quantities of <15%. The lower admixtures of pumpkin puree in apricot nectars and
      jams could be detected by the presence of syringic acid, a phenolic compound
      characteristic of the investigated pumpkins (Cucurbita pepo cv. Gleisdorff and
      Table Gold, Cucurbita maxima cv. Turkinja, and Cucurbita moschata cv. Argenta).
      Syringic acid was isolated from pumpkin puree and determined by using HPLC with
      diode array detection. By using the phenolic profile, undeclared pumpkin
      admixture (> or =5%) in the apricot nectars and jams could be proven.

PMID- 15941325
TI  - Study of the main constituents of some authentic hazelnut oils.
AB  - This paper describes the composition of authentic hazelnut oils obtained from
      nuts collected from five countries that are major suppliers of hazelnut oil. Oils
      were analyzed using standard methods for fatty acids, fatty acids in the
      triacylglycerol 2-position, tocopherols and tocotrienols, triacylglycerols,
      sterols, steradienes, and iodine value. The results were generally in good
      agreement with those of other publications. Tocotrienols, previously unreported
      in hazelnut oil, were detected in one sample. There were no major differences in
      the composition of oils from different countries. Roasting the nuts prior to
      pressing had little effect on oil composition.

PMID- 15941326
TI  - Study of the main constituents of some authentic walnut oils.
AB  - This paper describes the composition of walnut oils obtained from nuts collected
      from seven countries that are major suppliers of walnut oil. Oils were extracted
      from the nuts using small-scale industry pressing equipment and analyzed using
      standard methods for fatty acids, fatty acids in the triacylglycerol 2-position,
      tocopherols and tocotrienols, triacylglycerols, sterols, steradienes, and iodine
      value. Values for the composition of the sterols, triacylglycerols, fatty acids,
      iodine value, and tocopherol composition were generally in good agreement with
      the results of previous similar surveys. Tocotrienols were not detected in any
      sample. Steradienes (stigmastadiene, campestadiene, stigmastatriene, and
      campestatriene) were not detected in any oil.

PMID- 15941327
TI  - Production of fumonisin B and C analogues by several fusarium species.
AB  - Six strains of Fusarium verticillioides, two of F. oxysporum, one strain of F.
      proliferatum, and a strain of an unidentified species were cultured on maize
      patties and rice and evaluated for their ability to simultaneously produce
      fumonisin B (FB) and C (FC) series analogues. Fumonisins were quantified by LC-MS
      MS using positive ion electrospray ionization. FC1 provided characteristic
      fragment ions at m/z 690, 672, 654, 532, 514, and 338 corresponding to sequential
      loss of H2O and tricarboxylic acid moieties from the alkyl backbone, while FC3
      and FC4 provided equivalent product ions 16 and 32 amu lower than the
      corresponding FC1 fragments, respectively. All isolates cultured on maize
      produced FC4. All isolates except for that of F. proliferatum also produced FC1,
      and three of the six strains of F. verticillioides produced FC3. All isolates
      except those of F. oxysporum produced detectable amounts of FB1, FB2, and FB3.
      Isolates that produced fumonisin B analogues produced at least 10 fold more of
      the B series analogues than they did of the C series analogues. The results
      confirm that at least some strains of F. oxysporum produce FC, but not FB,
      fumonisin analogues and also suggest that the genetics and physiological
      regulation of fumonisin production may be more complicated than previously
      envisaged since some strains of F. verticillioides and F. proliferatum as well as
      the strain of the unidentified species can simultaneously produce both FB and FC
      analogues.

PMID- 15941328
TI  - Identification of 9(E),11(E)-18:2 fatty acid methyl ester at trace level in
      thermal stressed olive oils by GC coupled to acetonitrile CI-MS and CI-MS/MS, a
      possible marker for adulteration by addition of deodorized olive oil.
AB  - The olive oil market is suffering from sophisticated illegal treatments. One
      common adulteration process consists of the addition to virgin olive oil of lower
      quality oils, such as "lampante" oil, an inexpensive oil and with some
      organoleptic defects, which is then submitted to thermal deodorization under
      vacuum processes for removal of the undesired flavor components. Such a blending
      may not have a huge influence on the chemical composition and may not
      significantly affect the parameters usually checked as quality indicators,
      although the organoleptic properties may change. As a consequence, a major effort
      is being devoted to find reliable markers able to unmask such adulterations. We
      report here the complete characterization of a compound, detected at trace levels
      exclusively in thermal stressed oils, which could be a candidate marker for
      adulteration. The investigation, carried out by GC-MS and GC-MS/MS, provided its
      complete structure, including the stereochemistry, shown to be a 9(E),11(E)-18:2
      fatty acid methyl ester. Experimental data also confirmed the influence of both
      temperature and heating time on formation and concentration of this compound.

PMID- 15941329
TI  - Photodegradation of phosmet in wool wax models and on sheep wool: determination
      of wool wax bound phosmet by means of isotope ratio mass spectrometry.
AB  - The photochemical reactions of phosmet, an organophosphorus insecticide used for
      plant protection and for control of ectoparasites on productive livestock, were
      studied in the presence of wool wax. Induced by UV light, phosmet features
      numerous degradation pathways as well as photoaddition reactions with lipid
      structure moieties. In model irradiation experiments of phosmet in mixtures of
      solvents (cyclohexane, cyclohexene, 2-propanol) and fatty acid methyl esters
      (methyl stearate, methyl oleate, 12-hydroxymethyl stearate), both adjusted to the
      hydroxyl and iodine values of wool wax, half-lives were determined to be
      approximately 7 and 16 h, respectively. Irradiation of phosmet on crude sheep
      wool resulted in a degradation rate of 65% after 24 h. In tracer studies with
      stable isotope labeled phosmet ([15N]phosmet) in commercial lanolin and on raw
      sheep wool, employing a sunlight simulator and natural sunlight, wool wax bound
      phosmet was formed. After extraction and measurement by elemental
      analyzer/isotope ratio mass spectrometry, delta15N values of the phosmet-free
      wool wax fractions were notably increased as compared to the value of natural
      lanolin. Calculated from the delta15N values, an average of 13.9/15.6% (sunlight
      simulator/natural sunlight) was bound to wool wax lipids after irradiation of
      thin films of commercial lanolin. In experiments with sheep wool, 13.2 and 15.4%,
      respectively, were detected as wax-bound.

PMID- 15941330
TI  - Deodorization of swine manure using minced horseradish roots and peroxides.
AB  - Public concerns about offensive odors from livestock manures are on the rise and
      so is the pressure to develop practical ways to reduce the odors. The use of
      minced horseradish (Armoracia rusticanaL) roots (1:10 w/v plant tissue to swine
      slurry ratio), with calcium peroxide (CaO2 at 26 or 34 mM) or hydrogen peroxide
      (H2O2 at 34, 52, or 68 mM) for the deodorization of swine manure, was evaluated
      through a series of laboratory experiments. The principle underlying this
      deodorization method is the oxidation of odorants by the concerted action of
      horseradish peroxidase (present in the plant tissue) and peroxide that serves as
      an electron acceptor, followed by polymerization of phenolic odorants with a
      possible copolymerization or adsorption of other odorant compounds. The
      deodorization effect was assessed by a human panel and gas chromatography (GC).
      In the case of the GC method, 12 compounds commonly associated with malodor (7
      volatile fatty acids or VFAs, 3 phenolic compounds, and 2 indolic compounds) were
      used as odor indicators. Malodor assessment of the treated slurry by a human
      panel indicated a 50% reduction in odor intensity. GC results showed 100% removal
      of all phenolic odorants without reoccurrence for at least 72 h. In view of these
      data, using plant materials as enzyme carriers and peroxides as electron
      acceptors emerges as an effective approach to phenolic odor control in animal
      manure.

PMID- 15941331
TI  - Essential oil composition of Citrus meyerii Y. Tan. and Citrus medica L. cv.
      Diamante and their lemon hybrids.
AB  - In this paper we report the volatile fraction composition of Citrus meyerii Y.
      Tan. and Citrus medica L. cv. Diamante and two new lemon hybrids obtained by
      cross-breeding them with the tetraploid Citrus limon Burm. cv. Cavone. Both
      parent and hybrid oils were laboratory-extracted from the peel fruits and
      analyzed by HRGC-MS and HRGC-FID. Sixty-three components were fully characterized
      by mass spectra, linear retention indices, and injection of standards. The
      average composition as single components for all the oils analyzed is reported.
      Moreover, the data obtained were statistically analyzed. Since limonene is by far
      the main component of all the essential oils examined, analysis of variance and
      multivariate analysis gave interesting information on the similarities and
      differences between the oils analyzed. The new hybrid oils analyzed have
      potential commercial value because they could be an acceptable alternative to the
      valuable lemon oil.

PMID- 15941332
TI  - Precursors to damascenone: synthesis and hydrolysis of isomeric 3,9
      dihydroxymegastigma-4,6,7-trienes.
AB  - A series of four isomeric 3,9-dihydroxymegastigma-4,6,7-trienes, 8, has been
      prepared. The (3S,6R,9S) isomer of 8 proved to be identical to an isomer of this
      compound tentatively identified as an intermediate in the formation of
      damascenone from an allene triol. Each of the four isomers, when hydrolyzed
      independently of each other at pH 3.0 and 25 degrees C, produced product mixtures
      in which the major product was damascenone (1). Contrary to expectation, 3
      hydroxydamascone (5) was not observed in any of the hydrolyses. Consequently, the
      mechanism of formation of damascenone proposed earlier requires modification. In
      each hydrolysis, the product mixtures showed the presence of a second isomer of
      8, produced by epimerization during hydrolysis. Chiral analysis on a Cyclosil B
      column revealed that this epimerization was occurring at C(3) in each of the
      hydrolyses.

PMID- 15941333
TI  - Investigation of the presence of OH radicals in electrolyzed NaCl solution by
      electron spin resonance spectroscopy.
AB  - In the anode side of a two-chamber electrolyzer, electrolysis of a NaCl solution
      generates acidic electrolyzed oxidizing (EO) water, which exhibits bactericidal
      effects against a large number of pathogens. This study was undertaken to
      investigate whether OH radical species are present in EO water or are formed when
      EO water reacts with iron ions. Electron spin resonance spectroscopy (ESR)
      coupled with the spin trapping technique was used for the detection of free
      radicals. Samples of EO water were collected at 0.5, 1, 2, 3, and 5 min of
      electrolysis and immediately mixed with the spin trapping agent 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO). The 5,5-dimethyl-2-hydroxypyrrolidine-N-oxyl (DMPO-OH)
      spin adduct, characteristic of OH radicals, was not observed. Starting with 2-min
      electrolysis, a seven-line spectrum characteristic of 5,5-dimethyl-2-pyrrolidone
      N-oxyl (DMPOX) was formed. The reactions of EO water with Fe3+ and Fe2+ in the
      presence of DMPO yielded the spin adduct DMPO-OH. However, the addition of OH
      radical scavengers (ethanol and methanol) did not generate the characteristic
      DMPO-alkyl spin adducts. This indicated that the DMPO-OH spectrum was due to a
      nucleophilic addition of water to DMPO and not to trapping of OH radicals.

PMID- 15941334
TI  - 5,5-Dimethyl-2-pyrrolidone-N-oxyl formation in electron spin resonance studies of
      electrolyzed NaCl solution using 5,5-dimethyl-1-pyrroline-N-oxide as a spin
      trapping agent.
AB  - Electrolyzed oxidizing (EO) water has recently generated much interest as a
      disinfectant in the food industry. 5,5-Dimethyl-1-pyrroline-N-oxide (DMPO) is a
      spin trapping agent widely used in the electron spin resonance (ESR)
      characterization of oxygen-centered free radicals. The reaction between
      electrolyzed water, collected from the anode side of a two-chamber electrolyzer,
      and DMPO was investigated by ESR spectroscopy. Addition of DMPO to EO water
      generated an ESR spectrum identical to that of 5,5-dimethyl-2-pyrrolidone-N-oxyl
      (DMPOX), suggesting that a compound from EO water oxidized DMPO with the
      formation of DMPOX. To further investigate the electrolytically generated
      compound that oxidized DMPO, aqueous solutions of different sodium salts (sodium
      chloride, sodium citrate, and sodium iodide) with similar conductivities were
      electrolyzed. The DMPOX signal was not detected in the electrolyzed sodium
      citrate sample, suggesting that DMPOX formation in the electrolyzed NaCl sample
      might be due to an electrolytically generated chlorine species. A low DMPOX
      signal was also observed from the electrolyzed NaI sample, suggesting that a
      similar species obtained through the electrolysis of I- can also oxidize DMPO.
      Hypochlorous acid is proposed to oxidize the spin trap DMPO with the formation of
      DMPOX. In a neutral pH environment, electrolyzed water also oxidized DMPO to
      DMPOX. This is consistent with the DMPOX formation in the reaction of chlorine
      water (containing HOCl and Cl2) or sodium hypochlorite with DMPO.

PMID- 15941335
TI  - Fluorescence, browning index, and color in infant formulas during storage.
AB  - Free and total fluorescent compounds, browning index, and color formation were
      measured in milk-based powdered infant formulas (IF) during 2 years of storage at
      20 and 37 degrees C. The excitation spectra from 415 nm emission show three peaks
      (ex lambda1 = 270 nm, lambda2 = 325/315 nm, lambda3 = 350 nm) and from 347 nm
      excitation two emission peaks (415 and 520 nm), and no wavelength shifts were
      observed. Temperature and time of storage exert in general no significant effect
      on the development of fluorescence emission intensity and browning index.
      However, an important increase in pentodilysine was recorded-probably because of
      the iron and ascorbic acid contents of the samples-as well as in browning index
      in adapted IF. In both IF a color increase (deltaE) throughout storage was
      observed, this increase being greater in samples stored at 37 degrees C than in
      those stored at 20 degrees C. The increase in color with time fitted a linear
      regression model. Color appeared to be an indicator of sufficient sensitivity to
      measure the effect of temperature or storage time.

PMID- 15941336
TI  - Beta-glycosidase activity toward different glycosidic forms of isoflavones.
AB  - Isoflavones, a group of soybean components that significantly contribute to human
      health and disease prevention, exist in various chemical forms. The enzyme
      activity can be very sensitive to molecular structure; thus, the profile of the
      isoflavones can affect their rate of hydrolysis. The objective of this work was
      to study the beta-glycosidase activities toward isoflavone beta-glycosides and
      their conjugated forms. Hydrolysis experiments were conducted where beta
      glycosides and their conjugates were treated with beta-glycosidase. Results
      confirmed that beta-glycosidase can hydrolyze nonconjugated beta-glycosides into
      aglycones. However, when the enzyme amount and/or activity were limited,
      significant differences in enzyme activity toward the beta-glycosides were
      observed. On the other hand, beta-glycosidase was not effective in hydrolyzing
      the conjugated glycosides to their respective aglycones, even with increased
      levels of the enzyme and with prolonged incubation. The transformation of
      conjugated glycosides into their respective beta-glycosides will most likely
      result in increased hydrolysis rates and better absorption.

PMID- 15941337
TI  - Effect of the conservation procedure on the contents of phenolic compounds and
      organic acids in chanterelle (Cantharellus cibarius) mushroom.
AB  - To check the influence of the conservation procedure in the chemical composition
      of chanterelle mushroom, phenolic compounds and organic acids of samples
      preserved under four different conditions (drying, freezing, conservation in
      olive oil and in vinegar) were determined. Phenolics and organic acids were
      analyzed by HPLC-DAD and HPLC-UV, respectively. The results showed that
      chanterelle is characterized by the presence of six phenolic compounds (3-, 4-,
      and 5-O-caffeoylquinic acid, caffeic acid, p-coumaric acid, and rutin) and five
      organic acids (citric, ascorbic, malic, shikimic, and fumaric acids). Samples
      preserved in olive oil also exhibited hydroxytyrosol, tyrosol, luteolin, and
      apigenin, whereas conservation in vinegar led to the detection of hydroxytyrosol,
      tyrosol, and tartaric acid in the analyzed samples. The conservation procedures
      to which chanterelle samples were subjected seem to affect the qualitative and
      quantitative phenolics and organic acids profiles.

PMID- 15941338
TI  - Delphinidin 3-O-(2-O-beta-D-Glucopyranosyl-alpha-l-arabinopyranoside): a novel
      anthocyanin identified in Beluga black lentils.
AB  - A major anthocyanin was isolated from the acidified methanolic extract of Beluga
      black lentils by XAD7 column chromatography and preparative high-performance
      liquid chromatography. By means of electrospray ionization mass spectrometry and
      one- and two-dimensional nuclear magnetic resonance spectroscopy, its structure
      was determined to be delphinidin 3-O-(2-O-beta-D-glucopyranosyl-alpha-l
      arabinopyranoside).

PMID- 15941339
TI  - Antioxidant properties of malt model systems.
AB  - The aim of this study was to investigate the effect of kilning and roasting
      temperatures on antioxidant activity of malt model systems prepared from
      combinations of glucose, proline, and ferulic acid. Model systems (initial a(w) =
      0.09, 6% moisture) were heated at 60 degrees C for up to 24 h, at 90 degrees C
      for up to 120 min, and at 220 degrees C for up to 15 min. The antioxidant
      activity of the glucose-proline-ferulic acid model system increased significantly
      on heating at 60 degrees C for 24 h or at 90 degrees C for 120 min. In contrast,
      the glucose-proline, ferulic acid-glucose, and ferulic acid-proline systems
      presented either nonsignificantly increased or unchanged antioxidant activity.
      The antioxidant activity of both the glucose-proline-ferulic acid and glucose
      proline model systems increased significantly after heating at 220 degrees C for
      10 min, followed by a significant decrease at 15 min. The data suggest that (1)
      at 60 degrees C, ferulic acid reacts with Maillard reaction products, resulting
      in a significant increase in antioxidant activity; (2) at 90 degrees C, the
      antioxidant activity of the glucose-proline-ferulic system comes from both
      ferulic acid and Maillard reaction products; and (3) at 220 degrees C, the major
      contributors to antioxidant activity in glucose-proline-ferulic acid and glucose
      proline systems are glucose-proline reaction products.

PMID- 15941340
TI  - Harvest regimen optimization and essential oil production in five tansy
      (Tanacetum vulgare L.) genotypes under a northern climate.
AB  - Tansy (Tanacetum vulgare L.) was cultivated at the Norwegian Crop Research
      Institute at the Apelsvoll Research Centre, Division Kise, in the period from
      2000 to 2001. The study focused on different harvesting regimens for high biomass
      production and essential oil (EO) yield and quality. Two tansy genotypes from
      Canada (Richters and Goldsticks) and three Norwegian genotypes (Steinvikholmen,
      Alvdal, and Brumunddal) were studied. The Canadian genotypes reached a height of
      130-145 cm and showed a higher dry weight of aerial plant parts compared to the
      Norwegian plants in 2000. Similar oil yields could be observed for the Canadian
      types and genotype Steinvikholmen in the range of 30.8-34.6 L/ha when the plants
      were harvested twice during budding and before flowering after regrowth (year
      2001). In contrast, single harvesting at the full bloom stage resulted in higher
      oil yields, between 42.1 and 44.5 L/ha (Canadian genotypes), whereas 21.0-38.4
      L/ha was obtained from the Norwegian types. Tansy genotypes could be grouped into
      the following chemotypes: the mixed chemotypes Steinvikholmen (thujone-camphor),
      Alvdal (thujone-camphor-borneol), Goldsticks (thujone-camphor-chrysanthenyl
      type), and Brumunddal (thujone-camphor-1,8-cineole-bornyl acetate/borneol-alpha
      terpineol) and the distinct chemotype Richters, with average concentrations of
      (E)-chrysanthenyl acetate >40% in both leaf and flower EO.

PMID- 15941341
TI  - Chemical and physical properties of butterfat-vegetable oil blend spread prepared
      with enzymatically transesterified canola oil and caprylic acid.
AB  - Structured Lipid was synthesized from canola oil and caprylic acid with sn-1,3
      specific lipase from Rhizomucor miehei. Cold spreadable butter was made by
      blending butterfat with the SL at a weight ratio of 80:20. Its chemical and
      physical properties were compared with pure butter and butterfat-canola oil 80:20
      blend spread. The butterfat-SL blend had lower contents of hypercholesterolemic
      fatty acids (FAs) and the lowest atherogenic index (AI) as compared to the
      others. Melting and crystallization behaviors of butterfat-SL blend were similar
      to those of butterfat-canola oil blend above 0 degrees C. It showed solid fat
      contents (SFCs) similar to butterfat-canola oil blend but lower than pure
      butterfat. The butterfat-SL blend was shown to crystallize in the beta' form.
      There were no differences between the hardness of butterfat-SL blend spread and
      butterfat-canola oil blend spread. Rheological analysis showed that butterfat-SL
      blend spread lost its elastic behavior at 5 degrees C, a lower temperature than
      pure butter.

PMID- 15941342
TI  - Phosphorylation of ovalbumin by dry-heating in the presence of pyrophosphate:
      effect on protein structure and some properties.
AB  - Ovalbumin (OVA) was phosphorylated by dry-heating in the presence of
      pyrophosphate at pH 4.0 and 85 degrees C for 1 and 5 days, and the
      physicochemical and structural properties of phosphorylated OVA were
      investigated. The phosphorus content of OVA increased to 1.01% by
      phosphorylation, and the electrophoretic mobility of PP-OVA also increased.
      Although the solubility of dry-heated OVA decreased, the decrease was slightly
      depressed by phosphorylation. The circular dichroism spectra showed that the
      change of the secondary structure in the OVA molecule, as measured by alpha-helix
      content, was mild by phosphorylation. The exchange reaction between the
      sulfhydryl and disulfide groups was enhanced and the surface hydrophobicity of
      OVA increased by phosphorylation. The tryptophan fluorescence intensity of OVA
      decreased by phosphorylation, suggesting that the conformational change occurred
      in the OVA molecule by phosphorylation. Although the differential scanning
      calorimetry thermograms of OVA showed a lowering of the denaturation temperature
      from 78.3 to 70.1 degrees C by phosphorylation, the stability of OVA against heat
      induced insolubility at pH 7.0 was improved. The results indicated molten
      (partially unfolded) conformations of OVA formed by dry-heating in the presence
      of pyrophosphate.

PMID- 15941343
TI  - Characterization of bullet tuna myoglobin with reference to the thermostability
      structure relationship.
AB  - Myoglobin (Mb) was isolated from bullet tuna (Auxis rochei) skeletal muscle and
      characterized from the viewpoint of the thermostability-structure relationship.
      Differential scanning calorimetry (DSC) measurement showed that the
      thermostability of bullet tuna Mb was the lowest among all the scombridae fish
      Mbs so far examined. The highest value (72.8 degrees C) of melting temperature
      (Tm) was obtained at pH 6.52. alpha-Helical content at 10 degrees C was 34.5%,
      clearly lower than that of horse Mb (55.3%). The amino acid sequence was then
      deduced by cloning cDNA which encodes bullet tuna Mb. Bullet tuna Mb consisted of
      147 amino acids, and the sequence identity was very close to that of skipjack
      (Katsuwonus pelamis) Mb (91.8%). A few amino acid substitutions, which could be
      involved in stability difference of Mb, were recognized. By mass spectrometry of
      lysyl endoproteinase digest of Mb, the N-terminus was found to be acetylated like
      that of other fish Mbs.

PMID- 15941344
TI  - Effects of the combination of hydrophobic polypeptides, iso-alpha acids, and
      malto-oligosaccharides on beer foam stability.
AB  - The influence of hydrophobic polypeptides concentrated in beer foam, together
      with the composition of iso-alpha acids and the content of malto-oligosaccharides
      in beer on foam stability, has been investigated. The objective was to find out
      whether a shortage of one of these positive contributors to foam stability could
      be compensated for by an increased presence of another or whether optimum levels
      of each contributor is necessary. For that purpose, an image analysis method to
      evaluate beer foam quality was developed. The foam collapse time was the
      parameter chosen to group beers according to their foam stability. Profiles of
      hydrophobic polypeptides that concentrate in beer foam, iso-alpha acids, and
      malto-oligosaccharides of 14 beer brands were acquired by high-performance liquid
      chromatography. Principal component analysis (PCA) was performed to show the
      relationship between beer brands and its composition. Beers that contained
      propylene glycol alginate as a foam enhancer showed high foam stability except
      for one beer, which had a low content of hydrophobic polypeptides, thereby
      highlighting the requirement of threshold levels of hydrophobic polypeptides to
      obtain stable foam. The data of samples that were devoid of a foam additive were
      subjected to a discriminant statistical analysis. Foam stability declined in
      proportion to decreases in hydrophobic polypeptides and to a lesser extent to
      decreases in iso-alpha-acid contents. Apparently, the content of malto
      oligosaccharides were found to have no major influence on foam stability. The
      model of discriminate analysis was found to explain 100% of the variance in data
      with 85.2% success in classifying all samples according to the model, suggesting
      that foam stability is mainly governed by the beer constituents evaluated in this
      study.

PMID- 15941345
TI  - The relationship between the physicochemical properties of antioxidants and their
      ability to inhibit lipid oxidation in bulk oil and oil-in-water emulsions.
AB  - Chain-breaking antioxidants differ in their effectiveness at inhibiting lipid
      oxidation because of their chemical properties and physical location within a
      food. Our objective was how the physicochemical properties of four structurally
      related lipid-soluble antioxidants were related to their antioxidant activity.
      Antioxidants differed in the number of methyl (alpha-tocopherol and delta
      tocopherol) or hydroxyl (butylated hydroxytoluene (BHT) and 4-hydroxymethyl-2,6
      ditertiarybutylphenol) groups. Surface activity of the antioxidants was in the
      order of delta-tocopherol > alpha-tocopherol approximately 4-hydroxymethyl-2,6
      ditertiarybutylphenol > BHT. Free-radical scavenging activity was similar between
      alpha-tocopherol and delta-tocopherol as well as BHT and 4-hydroxymethyl-2,6
      ditertiarybutylphenol. In bulk menhaden oil, BHT was a more effective antioxidant
      than 4-hydroxymethyl-2,6-ditertiarybutylphenol while alpha-tocopherol was more
      effective than delta-tocopherol. In menhaden oil-in-water emulsions, BHT was a
      more effective antioxidant than 4-hydroxymethyl-2,6-ditertiarybutylphenol while
      delta-tocopherol was more effective than alpha-tocopherol. These results indicate
      that the surface activity and polarity of lipid-soluble antioxidants were not the
      only determinants of their antioxidant effectiveness in food lipids.

PMID- 15941346
TI  - Which polyphenolic compounds contribute to the total antioxidant activities of
      apple?
AB  - The antioxidant activities of eight apple cultivars were studied by using the
      ferric reducing/antioxidant power (FRAP), the beta-carotene-linoleic acid model
      system (beta-CLAMS), and the photochemiluminescent (PCL) assays. The antioxidant
      activity of apples is highly correlated to the total phenolic content (TPC)
      measured by the Folin-Ciocalteu method and the total polyphenolic index (TPI)
      obtained by HPLC. Extracts of the peel and flesh were analyzed and assayed
      separately. The FRAP activities of both peel and flesh extracts correlate well
      with the TPC (r = 0.95 and 0.99, respectively) and the TPI (r = 0.82 and 0.99,
      respectively). Similar results were found in the beta-CLAMS activities, showing
      correlation coefficients of r = 0.90 and 0.91 with the TPC for the peel and flesh
      extracts and of r = 0.90 and 0.84 with the TPI for the peel and flesh extracts,
      respectively. The antioxidant activity measured by the PCL assay was not
      correlated with TPC or TPI due to the lack of integratable lag phase in this
      method with the flavan-3-ols/procyanidins. Among the five major polyphenolic
      groups, flavan-3-ols/procyanidins had the highest positive correlation with the
      FRAP and beta-CLAMS activities: r = 0.84 and 0.88 for the peel extracts,
      respectively; and r = 0.98 and 0.87 for the flesh extracts, respectively. At
      individual compound level, epicatechin and procyanidin B2 were the major
      contributors to the antioxidant activity of apple. Hydroxycinnamic acids may have
      a significant role in the flesh.

PMID- 15941347
TI  - Effects of molecular weight and concentration of arabinoxylans on the membrane
      plugging.
AB  - In this paper, arabinoxylans from wheat were isolated, purified, and degraded
      into four fractions with different molecular weight. The distribution of particle
      size was employed to evaluate the membrane plugging by beer. These arabinoxylans
      fractions were added into arabinoxylan-free beer to investigate the effects of
      molecular weight and concentration on the distribution of particle size in beer.
      Results showed that the fraction of arabinoxylans retained by a 0.22-mum pore
      size membrane was more easily affected by shearing and arabinoxylan concentration
      than the fraction of arabinoxylans retained by a 0.45-mum membrane. The effects
      of shearing, pH, and ethanol concentration of beer on the particle size
      distribution of the highest molecular weight arabinoxylan fraction in beer were
      also examined. General linear models (GLM) equations indicated that there was a
      positive correlation between the particle size distributions of arabinoxylans and
      shearing and ethanol content, while high molecular weight arabinoxylans particle
      size retained by the 0.45-mum membrane was not significantly (p > 0.05)
      influenced by pH value. Scanning electron microscope (SEM) photos showed that
      membrane plugging was significantly affected by the molecular weight of the
      arabinoxylans.

PMID- 15941348
TI  - Determination of the phytoalexin resveratrol (3,5,4'-trihydroxystilbene) in
      peanuts and pistachios by high-performance liquid chromatographic diode array
      (HPLC-DAD) and gas chromatography-mass spectrometry (GC-MS).
AB  - The phytoalexin resveratrol (3,5,4'-trihydroxystilbene) in edible peanut (Arachis
      hypogaea L.) and pistachio (Pistacia vera L.) varieties grown in Turkey was
      analyzed by high-performance liquid chromatographic diode array and gas
      chromatography-mass spectrometric detection. trans-Resveratrol in six peanut
      varieties, five pistachio varieties, and four market samples ranged between 0.03
      and 1.92 microg/g. The Cerezlik 5025 peanut (1.92 +/- 0.01 microg/g) and Ohadi
      pistachio genotype (1.67 +/- 0.01 microg/g) had significantly higher trans
      resveratrol contents. Peanuts contained 0.03-1.92 microg/g (av = 0.84 microg/g)
      of trans-resveratrol, whereas pistachio contained 0.09-1.67 microg/g (av = 1.15
      microg/g). With exposure to UV light for 1 min, trans-resveratrol concentrations
      of samples ranged from 0.02 to 1.47 microg/g and those of cis-resveratrol from
      0.008 to 0.32 microg/g. The occurrence of resveratrol in peanut and pistachio was
      confirmed by total ion chromatograms (TIC) of
      bis[trimethylsilyl]trifluoroacetamide derivatives of resveratrol isomers and
      comparison of the mass spectral fragmentation data with those of a resveratrol
      standard. Formation of the cis-isomer in pistachios was higher than in peanuts.

PMID- 15941349
TI  - Acid-induced gelation of enzymatically modified, preheated whey proteins.
AB  - Low-pH whey protein gels are formulated using a sequential protocol of heat
      treatment, enzyme incubation, and cold-set acidification. The heat-induced
      disulfide and enzyme-catalyzed epsilon-(gamma-glutamyl)lysine linkages, both at
      neutral pH, produce a polymerized protein solution. The molecular weights of
      these samples show an exponential increase with protein concentration. The
      additional enzyme-catalyzed cross-links cause little change in molecular weight
      from that of heat-treated samples at low protein concentrations, indicating
      predominant intramolecular cross-linking. Enzyme treatment at higher protein
      concentration however causes increase in molecular weight, possibly due to
      formation of intermolecular cross-links. Acidification of the polymerized protein
      solutions through glucono-delta-lactone acid leads to gel formation at pH 4. The
      elastic (G') and viscous (G' ') moduli of gels with and without enzyme treatment
      show similar frequency dependence, indicating comparable microstructures,
      consistent with all samples exhibiting similar fractal dimensions of
      approximately 2 obtained independently using rheology and confocal microscopy. A
      substantial increase in fracture strain and stress of the gel is achieved by
      enzyme treatment. However, the elastic modulus (G') is only slightly larger after
      enzyme treatment compared with heat-treated samples. These results indicate that
      factors responsible for fracture properties may not be apparent in the gel
      microstructure and linear viscoelastic properties.

PMID- 15941350
TI  - Whey protein coating efficiency on surfactant-modified hydrophobic surfaces.
AB  - Whey protein oxygen-barrier coatings on peanuts are not effective, due to
      incomplete peanut-surface coverage, as well as some cracking and flaking of the
      coating. Addition of sorbitan laurate (Span 20) in the whey protein coating
      solution up to the critical micelle concentration (cmc) of 0.05% (w/w)
      significantly improved coating coverage to 88% of the peanut surface. Increasing
      the Span 20 concentration in the coating solution to 3 times the cmc (0.15% w/w)
      produced a substantial increase in peanut surface energy (>70 dyn/cm), indicating
      adsorption of the surfactant to the peanut surface. With this level of Span 20,
      the whey protein coating coverage on peanuts increased to 95%. These results
      suggest that a concentration of surfactant above the cmc in the coating solution
      is required for formation of self-assembled structures of surfactant molecules on
      peanut surfaces, which significantly increases the hydrophilicity, and thus
      coatability, of peanut surfaces.

PMID- 15941351
TI  - Antioxidant capacity of plasma after red wine intake in human volunteers.
AB  - Plasma antioxidant capacity (AC) has been assessed in eight healthy human
      volunteers after wine intake. Analytical methods used for evaluating AC included
      the ferric reducing ability of plasma (FRAP) and oxygen radical absorbance
      capacity using two different fluorescent probes, beta-phycoerythrin (ORAC-PE) and
      fluorescein (ORAC-FL). In addition, the concentrations of endogenous antioxidants
      such as uric acid, albumin, and bilirubin were determined. The suitability of
      analytical methods was evaluated with two different biological matrixes: plasma
      and serum. Plasma AC was determined before ingestion of 300 mL of red wine
      (baseline value) and 30, 55, and 120 min afterward. Maximum average increase in
      AC values was reached at 55 min. Plasma AC determined by ORAC-PE at time zero was
      significantly correlated with albumin concentration. Plasma AC determined with
      FRAP at time zero is well correlated with uric acid. Moreover, a good linear
      correlation was found between uric acid concentration and AC determined by FRAP
      in each volunteer. The maximum concentration of uric acid occurred after 55 min.
      Uric acid increase accounts for a nonnegligible part in FRAP values and must be
      evaluated when using this method for assessing AC in plasma.

PMID- 15941352
TI  - Phenolic antioxidants richly contained in corn bran are slightly bioavailable in
      rats.
AB  - Phenolic acids (PAs) have been shown to be beneficial to human health and are
      found most abundantly in corn bran ( approximately 4%, w/w), one of the main
      dietary fibers. This study therefore evaluated the bioavailabilities of phenolic
      antioxidants ferulic acid (FA) and p-coumaric acid (PCA) in refined corn bran
      (RCB) by determining their recovery in the plasma, urine, and feces of rats fed a
      single meal of a RCB diet containing 5% RCB or adapted to the RCB diet for 10
      days. In both studies, 0.4-0.5% of ingested FA and 1.2-2.3% of ingested PCA were
      recovered in rat urine. By contrast, approximately 81% of FA and approximately
      64% of PCA ingested with the single meal were excreted through the rat feces
      within 3 days after the ingestion. On the other hand, after rats were fed the RCB
      diet, total FA (all forms of FA) was recovered in plasma at a concentration of
      35.0 +/- 2.0 microg/L, total FA and total PCA were excreted through urine at
      levels of 155.4 +/- 5.8 and 50.9 +/- 6.6 microg/day, respectively. These
      parameters showed no significant change (P = 0.93, 0.09, and 0.66, respectively)
      after rats were fed the RCB diet continuously for up to 10 days. These results
      suggest that the PAs in RCB are bioavailable in rats. Their bioavailabilities,
      however, are relatively low compared with their high content in RCB and not
      improved by the adaptation for 10 days to the enriched RCB diet. Additionally,
      comparison with the results of other studies revealed that high contents of FA
      and, especially, diferulic acids in cereal bran, which act as cross-links between
      bran cell wall polysaccharides, may not improve but, rather, limit the
      bioavailabilities of PAs in vivo.

PMID- 15941353
TI  - Literature data may underestimate the actual antioxidant capacity of cereals.
AB  - Several recent articles have reported a significant antioxidant capacity of
      cereal products, determined in methanolic and ethanolic extracts. The aim of this
      work was to conduct an assessment of the antioxidant capacity of cereals using
      both chemical and in vitro digestive enzymatic extraction of antioxidants. Ferric
      reducing power (FRAP) and free radical scavenging capacity (DPPH) methods were
      used to determine the antioxidant capacity in wheat flour, bread, raw and boiled
      rice, wheat bran, and oat bran. The most efficient antioxidant extraction was
      achieved by using successively acidic methanol/water (50:50 v/v, pH 2) and
      acetone/water (70:30 v/v). The antioxidant capacity in these extracts ranged from
      1.1 to 4.4 micromol Trolox/g dw. A significant amount of hydrolyzable phenolics
      with a high antioxidant capacity (from 5 to 108 micromol Trolox/g dw) was found
      in the residues of this aqueous-organic extraction. The antioxidant capacities of
      these nonextractable polyphenols are usually ignored in the literature, although
      they may have an antioxidant role in the gastrointestinal tract, especially after
      colonic fermentation, and may be fermentated to active metabolites. On the other
      hand, in vitro digestive enzymatic extracts obtained by enzymatic treatments that
      mimic conditions in the gastrointestinal tract showed that the amount of
      antioxidants released by the cereal matrix into the human intestine may be higher
      than the one that can be expected from measurements in the usual aqueous-organic
      extracts.

PMID- 15941354
TI  - Antioxidant and membrane effects of procyanidin dimers and trimers isolated from
      peanut and cocoa.
AB  - The antioxidant and membrane effects of dimer (Dim) and trimer (Trim)
      procyanidins isolated from cocoa (Theobroma cacao) (B- and C-bonded) and peanut
      (Arachis hypogea L.) skin (A-bonded) were evaluated in phosphatidyl choline
      liposomes. When liposomes were oxidized with a steady source of oxidants, the
      above dimers and trimers inhibited to a similar extent lipid oxidation in a
      concentration (0.33-5 microM)-dependent manner. With respect to membrane effects,
      Dim A1, Dim B, Trim A, and Trim C increased (Dim A1 = Dim B and Trim A = Trim C),
      while Dim A2 decreased, membrane surface potential. All of the procyanidins
      tested decreased membrane fluidity as determined by fluorescent probes at the
      water-lipid interface, an effect that extended into the hydrophobic region of the
      bilayer. Both dimers and trimers protected the lipid bilayer from disruption by
      Triton X-100. The magnitude of the protection was Dim A1 > Dim A2 > Dim B and
      Trim C > Trim A. Thus, dimers and trimers can interact with membrane
      phospholipids, presumably with their polar headgroup. As a consequence of this
      interaction, they can provide protection against the attack of oxidants and other
      molecules that challenge the integrity of the bilayer.

PMID- 15941355
TI  - The evolution of norms.

PMID- 15941356
TI  - Functional genomics thickens the biological plot.

PMID- 15941357
TI  - Engineering a dimeric caspase-9: a re-evaluation of the induced proximity model
      for caspase activation.
AB  - Caspases are responsible for the execution of programmed cell death (apoptosis)
      and must undergo proteolytic activation, in response to apoptotic stimuli, to
      function. The mechanism of initiator caspase activation has been generalized by
      the induced proximity model, which is thought to drive dimerization-mediated
      activation of caspases. The initiator caspase, caspase-9, exists predominantly as
      a monomer in solution. To examine the induced proximity model, we engineered a
      constitutively dimeric caspase-9 by relieving steric hindrance at the dimer
      interface. Crystal structure of the engineered caspase-9 closely resembles that
      of the wild-type (WT) caspase-9, including all relevant structural details and
      the asymmetric nature of two monomers. Compared to the WT caspase-9, this
      engineered dimer exhibits a higher level of catalytic activity in vitro and
      induces more efficient cell death when expressed. However, the catalytic activity
      of the dimeric caspase-9 is only a small fraction of that for the Apaf-1
      activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity
      of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1
      dependent manner. These findings suggest that dimerization of caspase-9 may be
      qualitatively different from its activation by Apaf-1, and in conjunction with
      other evidence, posit an induced conformation model for the activation of
      initiator caspases.

PMID- 15941359
TI  - When two is better than one: elements of intravital microscopy.

PMID- 15941358
TI  - Neural correlates of executive control in the avian brain.
AB  - Executive control, the ability to plan one's behaviour to achieve a goal, is a
      hallmark of frontal lobe function in humans and other primates. In the current
      study we report neural correlates of executive control in the avian nidopallium
      caudolaterale, a region analogous to the mammalian prefrontal cortex. Homing
      pigeons (Columba livia) performed a working memory task in which cues instructed
      them whether stimuli should be remembered or forgotten. When instructed to
      remember, many neurons showed sustained activation throughout the memory period.
      When instructed to forget, the sustained activation was abolished. Consistent
      with the neural data, the behavioural data showed that memory performance was
      high after instructions to remember, and dropped to chance after instructions to
      forget. Our findings indicate that neurons in the avian nidopallium caudolaterale
      participate in one of the core forms of executive control, the control of what
      should be remembered and what should be forgotten. This form of executive control
      is fundamental not only to working memory, but also to all cognition.

PMID- 15941360
TI  - Pseudoknots: RNA structures with diverse functions.

PMID- 15941361
TI  - Guidelines for negotiating scientific collaboration.

PMID- 15941362
TI  - Sleep in individuals with Angelman syndrome: parent perceptions of patterns and
      problems.
AB  - The diagnostic criteria for Angelman syndrome includes sleep disturbance as an
      associated characteristic. There are, however, few researchers who have examined
      sleep problems in this population. Our goal in this study was to better
      characterize the sleep patterns and problems in individuals with Angelman
      syndrome. Parents of 339 individuals between the ages of 3 and 22 completed a
      previously validated sleep questionnaire. Results confirmed that a variety of
      sleep problems exist in a significant portion of individuals with Angelman
      syndrome, most prominently in the areas of sleep initiation, sleep duration,
      reliance on sleep facilitators, being awakened by loud noises, and being
      disoriented when aroused. Developmental trends, syndrome specificity of findings,
      clinical implications, and directions for future research are discussed.

PMID- 15941363
TI  - Etiology of mental retardation in children referred to a tertiary care center: a
      prospective study.
AB  - A prospective assessment following a step-wise protocol in 281 patients with
      unexplained cognitive delay was used to assess diagnostic possibilities.
      Diagnostic procedures were complex and required a multidisciplinary approach. One
      third of diagnoses was established based on clinical history and physical exam
      only; for another third, clinical history and physical exam provided essential
      clues for additional investigations; and a third were established by additional
      investigations only. The likelihood to reach a diagnosis did not depend on the
      severity of mental retardation. We found that in a tertiary care center, a
      diagnosis can be established in 1 out of every 2 patients. Clinical history and
      physical examination are the most important instruments to reach a diagnosis.

PMID- 15941364
TI  - Aging in adults with intellectual disabilities.
AB  - A cross-sequential design was used to examine changes related to aging in adults
      with and without Down syndrome (ns = 55 and 75, respectively). Adults received
      yearly neuropsychological and medical evaluations. Support for precocious aging
      in adults with Down syndrome was evident only on a test of verbal fluency, with
      weaker support obtained on a test of fine-motor skills. Cross-sectional age
      differences for all adults were obtained on tests of memory and community living
      skills. General intellectual level, gender, and psychiatric status were
      consistently related to performance, indicating the need to examine such
      mediating variables in studies on aging.

PMID- 15941365
TI  - Perceptions of stress and coping strategies among adults with mild mental
      retardation: insight into psychological distress.
AB  - Stress, coping, perceptions of control, and psychological distress of 88 adults
      with mild mental retardation were assessed. Stressful interpersonal interactions
      and concerns over personal competencies occurred most frequently. Frequency and
      stress impact were positively associated with a composite score of psychological
      distress. Active coping was associated with less psychological distress than
      distraction or avoidant coping. Perceptions of control were positively related to
      active coping and negatively related to avoidant coping. Active coping was
      related to less psychological distress when used with perceptions of high control
      than with perceptions of low control. Decreasing opportunities for stress and
      increasing accurate perceptions of control and subsequently active coping may
      reduce psychological distress among people with mild mental retardation.

PMID- 15941366
TI  - Cross-cultural study of quality of life indicators.
AB  - The concept of quality of life is increasingly being used internationally in the
      field of intellectual disabilities. We surveyed three respondent groups
      representing five geographical groupings on the importance and use of the 24 core
      quality of life indicators most commonly reported in the international quality of
      life literature. Results suggest (a) similar profiles on importance and use
      across respondent and geographical groups, but differences in the frequency per
      response category; (b) significant differences in mean quality of life importance
      and use scores for both respondent and geographic groupings; and (c) factors on
      importance and use generally grouped into eight core quality of life domains.
      Results are discussed in reference to the etic (universal) and emic (culture
      bound) properties of the quality of life concept.

PMID- 15941367
TI  - Nonverbal requesting and problem-solving by toddlers with down syndrome.
AB  - The association between nonverbal requesting (as measured by the Early Social
      Communication Scales) and problem-solving skills (as measured by an object
      retrieval task) was examined in 16 toddlers who had Down syndrome, 18 toddlers
      with developmental disabilities of mixed etiologies, and 19 typically developing
      infants and toddlers. Toddlers with Down syndrome showed fewer instrumental
      requests than did those in the typically developing group, but equal numbers of
      social routine requests. Toddlers with Down syndrome also showed poorer problem
      solving strategies and received more help than children in both comparison groups
      on the object-retrieval task. Results showed a significant association between
      instrumental requests and problem-solving in the Down syndrome group.
      Implications for strengthening problem-solving skills in Down syndrome are
      discussed.

PMID- 15941368
TI  - Self-injurious behavior and sequential analysis: context matters.

PMID- 15941371
TI  - Deficits in decision-making in head injury survivors.
AB  - Many survivors of head injury suffer chronic personality changes, such as
      increased impulsivity and a lack of insight and poor judgment. These changes are
      well recognized and likely to affect the ability to make decisions. However,
      systematic investigations into their nature have been limited. This study aims to
      explore the nature of decision making in head injury survivors using a
      computerized task. Forty-three head injury survivors and a group of 29 matched
      controls completed the computerized task. The task required participants to make
      a probability-based choice and to further qualify this choice with an associated
      "bet." This betting component allows an assessment of the participant's level of
      confidence in the decision, via the affective evaluation of its possible
      consequences in terms of points won or lost. The survivors were found to be slow
      at making the probability- based choice. Whilst at highly favorable odds, the
      survivors chose the most likely option in a similar manner to the controls, they
      chose the most likely option less often than the controls at less favorable odds.
      Examination of the survivors' betting behavior revealed that they responded
      impulsively compared to controls. This pattern of prolonged decision making and
      poor quality of decisions is similar to that found in patients with orbitofrontal
      cortex lesions, whilst impulsive betting has been associated with abnormalities
      of the dopamine system. These complex deficits in decision making may contribute
      to difficulties with poor judgment and inhibition in head injury survivors.

PMID- 15941372
TI  - Efficacy of standard trauma craniectomy for refractory intracranial hypertension
      with severe traumatic brain injury: a multicenter, prospective, randomized
      controlled study.
AB  - To compare the effect of standard trauma craniectomy (STC) versus limited
      craniectomy (LC) on the outcome of severe traumatic brain injury (TBI) with
      refractory intracranial hypertension, we conducted a study at five medical
      centers of 486 patients with severe TBI (Glasgow Coma Scale score </= 8) and
      refractory intracranial hypertension. In all 486 cases, refractory intracranial
      hypertension, caused by unilateral massive frontotemporoparietal contusion,
      intracerebral/subdural hematoma, and brain edema, was confirmed on a CT scan. The
      patients were randomly divided into two groups, one of which underwent STC (n =
      241) with a unilateral frontotemporoparietal bone flap (12 x 15 cm), and the
      second of which underwent LC (n = 245) with a routine temporoparietal bone flap
      (6 x 8 cm). At 6-month follow-up, 96 patients (39.8%) in the STC group had a
      favorable outcome on the basis of the Glasgow Outcome Scale, including 62
      patients who had a good recovery and 34 who showed moderate deficits. Another 145
      patients (60.2%) in the STC group had an unfavorable outcome, including 73 with
      severe deficits, nine with persistent vegetative status, and 63 who died. By
      comparison, only 70 patients (28.6%) in the LC group had a favorable outcome,
      including 41 who had a good recovery and 29 who had moderate deficits. Another
      175 patients (71.4%) in the LC group had an unfavorable outcome, including 82
      with severe deficits, seven with persistent vegetative status, and 86 who died (p
      < 0.05). In addition to these findings, the incidence of delayed intracranial
      hematoma, incisional hernia, and CSF fistula was lower in the STC group than in
      the LC group (p < 0.05), although the incidence of acute encephalomyelocele,
      traumatic seizure, and intracranial infection was not significantly different in
      the two groups (p > 0.05). The results of the study indicate that STC
      significantly improves outcome in severe TBI with refractory intracranial
      hypertension resulting from unilateral frontotemporoparietal contusion with or
      without intracerebral or subdural hematoma. This suggests that STC, rather than
      LC, be recommended for such patients.

PMID- 15941373
TI  - Rapid discovery of putative protein biomarkers of traumatic brain injury by SDS
      PAGE-capillary liquid chromatography-tandem mass spectrometry.
AB  - We report the rapid discovery of putative protein biomarkers of traumatic brain
      injury (TBI) by SDS-PAGE-capillary liquid chromatography-tandem mass spectrometry
      (SDS-PAGE-Capillary LC-MS(2)). Ipsilateral hippocampus (IH) samples were
      collected from naive rats and rats subjected to controlled cortical impact (a
      rodent model of TBI). Protein database searching with 15,558 uninterpreted MS(2)
      spectra, collected in 3 days via data-dependent capillary LC-MS(2) of pooled
      cyanine dye-labeled samples separated by SDS-PAGE, identified more than 306
      unique proteins. Differential proteomic analysis revealed differences in protein
      sequence coverage for 170 mammalian proteins (57 in naive only, 74 in injured
      only, and 39 of 64 in both), suggesting these are putative biomarkers of TBI.
      Confidence in our results was obtained by the presence of several known
      biomarkers of TBI (including alphaII-spectrin, brain creatine kinase, and neuron
      specific enolase) in our data set. These results show that SDS-PAGE prior to in
      vitro proteolysis and capillary LC-MS(2) is a promising strategy for the rapid
      discovery of putative protein biomarkers associated with a specific physiological
      state (i.e., TBI) without a priori knowledge of the molecules involved.

PMID- 15941374
TI  - Enhanced hippocampal neurogenesis by intraventricular S100B infusion is
      associated with improved cognitive recovery after traumatic brain injury.
AB  - Evidence of injury-induced neurogenesis in the adult hippocampus suggests that an
      endogenous repair mechanism exists for cognitive dysfunction following traumatic
      brain injury (TBI). One factor that may be associated with this restoration is
      S100B, a neurotrophic/mitogenic protein produced by astrocytes, which has been
      shown to improve memory function. Therefore, we examined whether an
      intraventricular S100B infusion enhances neurogenesis within the hippocampus
      following experimental TBI and whether the biological response can be associated
      with a measurable cognitive improvement. Following lateral fluid percussion or
      sham injury in male rats (n = 60), we infused S100B (50 ng/h) or vehicle into the
      lateral ventricle for 7 days using an osmotic micro-pump. Cell proliferation was
      assessed by injecting the mitotic marker bromodeoxyuridine (BrdU) on day 2
      postinjury. Quantification of BrdU-immunoreactive cells in the dentate gyrus
      revealed an S100B-enhanced proliferation as assessed on day 5 post-injury (p <
      0.05), persisting up to 5 weeks (p < 0.05). Using cell-specific markers, we
      determined the relative numbers of these progenitor cells that became neurons or
      glia and found that S100B profoundly increased hippocampal neurogenesis 5 weeks
      after TBI (p < 0.05). Furthermore, spatial learning ability, as assessed by the
      Morris water maze on day 30-34 post-injury, revealed an improved cognitive
      performance after S100B infusion (p < 0.05). Collectively, our findings indicate
      that an intraventricular S100B infusion induces neurogenesis within the
      hippocampus, which can be associated with an enhanced cognitive function
      following experimental TBI. These observations provide compelling evidence for
      the therapeutic potential of S100B in improving functional recovery following
      TBI.

PMID- 15941375
TI  - Progesterone differentially regulates pro- and anti-apoptotic gene expression in
      cerebral cortex following traumatic brain injury in rats.
AB  - Although the administration of progesterone has been shown to be neuroprotective
      in experimental models of traumatic brain injury (TBI), the mechanisms for this
      beneficial effect are still poorly understood. The present study examined the
      effects of progesterone on mRNA and protein levels of the Bcl-2 apoptosis
      regulatory genes, bax, bad, bcl-2, and bcl-x(L), in cerebral cortex after TBI.
      Male Sprague-Dawley rats were subjected to either sham surgery or lateral fluid
      percussion brain injury of moderate severity (2.4-2.6 atm). Within 1 h post
      surgery, progesterone (4 mg/kg) or vehicle (corn oil) administration was
      initiated for 1-7 days postoperatively. Our results indicate that bax and bad
      mRNA levels and Bax and Bad protein expression in the ipsilateral, injured
      cerebral cortex were significantly elevated post-TBI, while mRNA levels of bcl-2
      and bcl-x(L) or Bcl-2 and Bcl-x(L) protein expression were not changed. Under the
      sham-treated condition, progesterone significantly increased mRNA levels of the
      anti-apoptotic gene, bcl-2, but down-regulated pro-apoptotic gene expression (bax
      and bad) in cerebral cortex. After TBI, progesterone treatment reduced bax and
      bad mRNA levels in the ipsilateral cerebral cortex of TBI rats, and decreased Bax
      and Bad protein levels. In addition, bcl-2 and bcl-x(L) mRNA levels, as well as
      Bcl-2 and Bcl-x(L) protein expression, were increased by progesterone in TBI
      injured cortex. These data indicate that one of the neuroprotective mechanisms of
      progesterone may be related to its differential regulation of apoptotic signals.

PMID- 15941376
TI  - Lack of a gender difference in post-traumatic neurodegeneration in the mouse
      controlled cortical impact injury model.
AB  - Recent studies using a mouse model of weight-drop-induced "diffuse" traumatic
      brain injury (TBI) have demonstrated a substantial gender difference in the time
      course and magnitude of post-traumatic neurodegeneration following a severe level
      of injury. The time of maximal damage, as assessed by the de Olmos aminocupric
      silver staining method, occurred at 72 h in male mice, whereas the peak of
      neurodegeneration was not observed until 14 days in females and was less in
      magnitude compared to males. This difference, favoring females, has been
      postulated to relate to the neuroprotective actions of estrogen and progesterone.
      In the presently reported experiments, we compared the time course and peak of
      neurodegeneration in male and female mice after a severe level of "focal"
      controlled cortical impact (CCI; 1 mm, 3.5 m/sec) TBI using the same strain (CF
      1) and weight (29-31 g) as employed in the "diffuse" TBI study. The volume of
      silver staining was measured using image analysis methods at 24, 48, and 72 h,
      and 1, 2 and 4 weeks. In male and female mice, a significant increase in
      neurodegeneration was observed at 24 h, and the volume was not significantly
      different between the two genders. In both gender groups, the maximal
      neurodegeneration was seen at 48 h after injury. Although the female mice
      exhibited a trend toward higher mean volumes of silver staining, this difference
      was not significantly different compared to males. Furthermore, the rate of
      resolution of staining between 48 h and 4 weeks was similar. However, injured
      females still exhibited a significantly higher volume of staining compared to
      sham, non-injured females at 4 weeks, whereas the difference in staining volume
      between sham and injured males was no longer significant at that time point.
      These results show that, following a "focal" CCI, there is no gender difference
      that favors females, in contrast to that seen with the "diffuse" injury paradigm.
      The disparity between the effects of gender in the two models may be due to the
      fact that, in the "focal" CCI model, the timing of post-traumatic
      neurodegeneration is significantly more rapid than that seen in the "diffuse"
      model, which may overwhelm the neuroprotective effects of estrogen and
      progesterone and obscure the appearance of a gender difference.

PMID- 15941377
TI  - Histopathological and behavioral characterization of a novel cervical spinal cord
      displacement contusion injury in the rat.
AB  - Cervical contusive trauma accounts for the majority, of human spinal cord injury
      (SCI), yet experimental use of cervical contusion injury models has been limited.
      Considering that (1) the different ways of injuring the spinal cord (compression,
      contusion, and transection) induce very different processes of tissue damage and
      (2) the architecture of the spinal cord is not uniform, it is important to use a
      model that is more clinically applicable to human SCI. Therefore, in the current
      study we have developed a rat model of contusive, cervical SCI using the
      Electromagnetic Spinal Cord Injury Device (ESCID) developed at Ohio State
      University (OSU) to induce injury by spinal cord displacement. We used the device
      to perform mild, moderate and severe injuries (0.80, 0.95, and 1.1 mm
      displacements, respectively) with a single, brief displacement of <20 msec upon
      the exposed dorsal surface of the C5 cervical spinal cord of female (180-200 g)
      Fischer rats. Characterization of the model involved the analysis of the temporal
      histopathological progression of the injury over 9 weeks using histochemical
      stains to analyze white and gray mater integrity and immunohistochemistry to
      examine cellular changes and physiological responses within the injured spinal
      cord. Accompanying the histological analysis was a comprehensive determination of
      the behavioral functionality of the animals using a battery of motor tests.
      Characterization of this novel model is presented to enable and encourage its
      future use in the design and experimental testing of therapeutic strategies that
      may be used for human SCI.

PMID- 15941378
TI  - A unilateral section of the corticospinal tract at cervical level in primate does
      not lead to measurable cell loss in motor cortex.
AB  - The effects of a unilateral interruption of the dorsolateral funiculus at
      cervical level on the survival of neurons in the motor cortex were investigated
      in macaque monkeys. The lesion was made on the left side at the transition region
      between the 7(th) and 8(th) cervical segments, above the motoneurons controlling
      hand muscles. As a result, the homolateral hand became paretic, although an
      incomplete recovery of manual dexterity took place during 2 months post-lesion. A
      quantitative anatomical assessment of pyramidal neurons in layer V was performed
      in the hindlimb area of the primary motor cortex and in the supplementary motor
      area (SMA proper). The pyramidal neurons were visualized using the marker SMI-32
      and thus included the subpopulation of corticospinal neurons. These quantitative
      data demonstrated that the vast majority of the axotomized corticospinal (CS)
      neurons did not degenerate. Rather, their somata shrank, compared to the opposite
      hemisphere or to intact monkeys. This conclusion is in contrast to some previous
      studies in monkeys that argued for a substantial degeneration of motor cortex
      neurons as a result of transection of the corticospinal tract; yet in agreement
      with others that concluded the survival of most CS neurons. The survival of the
      majority of CS axotomized neurons is also consistent with the observation of
      numerous CS axons 1 mm above the cervical hemisection.

PMID- 15941379
TI  - Cutting anthropic knots and the rise of O2.

PMID- 15941380
TI  - Raman imagery: a new approach to assess the geochemical maturity and biogenicity
      of permineralized precambrian fossils.
AB  - Laser-Raman imagery is a non-intrusive, non-destructive analytical technique,
      recently introduced to Precambrian paleobiology, that can be used to demonstrate
      a one-to-one spatial correlation between the optically discernible morphology and
      kerogenous composition of permineralized fossil microorganisms. Made possible by
      the submicron-scale resolution of the technique and its high sensitivity to the
      Raman signal of carbonaceous matter, such analyses can be used to determine the
      chemical-structural characteristics of organic-walled microfossils and associated
      sapropelic carbonaceous matter in acid-resistant residues and petrographic thin
      sections. Here we use this technique to analyze kerogenous microscopic fossils
      and associated carbonaceous sapropel permineralized in 22 unmetamorphosed or
      little-metamorphosed fine-grained chert units ranging from approximately 400 to
      approximately 2,100 Ma old. The lineshapes of the Raman spectra acquired vary
      systematically with five indices of organic geochemical maturation: (1) the
      mineral-based metamorphic grade of the fossil-bearing units; (2) the fidelity of
      preservation of the fossils studied; (3) the color of the organic matter
      analyzed; and both the (4) H/C and (5) N/C ratios measured in particulate
      kerogens isolated from bulk samples of the fossil-bearing cherts. Deconvolution
      of relevant spectra shows that those of relatively well-preserved permineralized
      kerogens analyzed in situ exhibit a distinctive set of Raman bands that are
      identifiable also in hydrated organic-walled microfossils and particulate
      carbonaceous matter freed from the cherts by acid maceration. These distinctive
      Raman bands, however, become indeterminate upon dehydration of such specimens. To
      compare quantitatively the variations observed among the spectra measured, we
      introduce the Raman Index of Preservation, an approximate measure of the
      geochemical maturity of the kerogens studied that is consistent both with the
      five indices of organic geochemical alteration and with spectra acquired from
      fossils experimentally heated under controlled laboratory conditions. The results
      reported provide new insight into the chemical-structural characteristics of
      ancient carbonaceous matter, the physicochemical changes that accompany organic
      geochemical maturation, and a new criterion to be added to the suite of evidence
      by which to evaluate the origin of minute fossil-like objects of possible but
      uncertain biogenicity.

PMID- 15941381
TI  - Vegetation's red edge: a possible spectroscopic biosignature of extraterrestrial
      plants.
AB  - Earth's deciduous plants have a sharp order-of-magnitude increase in leaf
      reflectance between approximately 700 and 750 nm wavelength. This strong
      reflectance of Earth's vegetation suggests that surface biosignatures with sharp
      spectral features might be detectable in the spectrum of scattered light from a
      spatially unresolved extrasolar terrestrial planet. We assess the potential of
      Earth's step-function-like spectroscopic feature, referred to as the "red edge,"
      as a tool for astrobiology. We review the basic characteristics and physical
      origin of the red edge and summarize its use in astronomy: early spectroscopic
      efforts to search for vegetation on Mars and recent reports of detection of the
      red edge in the spectrum of Earthshine (i.e., the spatially integrated scattered
      light spectrum of Earth). We present Earthshine observations from Apache Point
      Observatory (New Mexico) to emphasize that time variability is key to detecting
      weak surface biosignatures such as the vegetation red edge. We briefly discuss
      the evolutionary advantages of vegetation's red edge reflectance, and speculate
      that while extraterrestrial "light-harvesting organisms" have no compelling
      reason to display the exact same red edge feature as terrestrial vegetation, they
      might have similar spectroscopic features at different wavelengths than
      terrestrial vegetation. This implies that future terrestrial-planet
      characterizing space missions should obtain data that allow time-varying, sharp
      spectral features at unknown wavelengths to be identified. We caution that some
      mineral reflectance edges are similar in slope and strength to vegetation's red
      edge (albeit at different wavelengths); if an extrasolar planet reflectance edge
      is detected care must be taken with its interpretation.

PMID- 15941382
TI  - Recurrent isolation of hydrogen peroxide-resistant spores of Bacillus pumilus
      from a spacecraft assembly facility.
AB  - While the microbial diversity of a spacecraft assembly facility at the Jet
      Propulsion Laboratory (Pasadena, CA) was being monitored, H2O2-resistant
      bacterial strains were repeatedly isolated from various surface locations. H2O2
      is a possible sterilant for spacecraft hardware because it is a low-temperature
      process and compatible with various modern-day spacecraft materials, electronics,
      and components. Both conventional biochemical testing and molecular analyses
      identified these strains as Bacillus pumilus. This Bacillus species was found in
      both unclassified (entrance floors, anteroom, and air-lock) and classified
      (floors, cabinet tops, and air) locations. Both vegetative cells and spores of
      several B. pumilus isolates were exposed to 5% liquid H2O2 for 60 min. Spores of
      each strain exhibited higher resistance than their respective vegetative cells to
      liquid H2O2. Results indicate that the H2O2 resistance observed in both
      vegetative cells and spores is strain-specific, as certain B. pumilus strains
      were two to three times more resistant than a standard Bacillus subtilis
      dosimetry strain. An example of this trend was observed when the type strain of
      B. pumilus, ATCC 7061, proved sensitive, whereas several environmental strains
      exhibited varying degrees of resistance, to H2O2. Repeated isolation of H2O2
      resistant strains of B. pumilus in a clean-room is a concern because their
      persistence might potentially compromise life-detection missions, which have very
      strict cleanliness and sterility requirements for spacecraft hardware.

PMID- 15941383
TI  - Iron meteorites can support the growth of acidophilic chemolithoautotrophic
      microorganisms.
AB  - Chemolithoautotrophy based on reduced inorganic minerals is considered a
      primitive energy transduction system. Evidence that a high number of meteorites
      crashed into the planet during the early period of Earth history led us to test
      the ability of iron-oxidizing bacteria to grow using iron meteorites as their
      source of energy. Here we report the growth of two acidophilic iron-oxidizing
      bacteria, Leptospirillum ferrooxidans and Acidithiobacillus ferrooxidans, on a
      piece of the Toluca meteorite as the only source of energy. The alteration of the
      surface of the exposed piece of meteorite, the solubilization of its oxidized
      metal constituents, mainly ferric iron, and the formation of goethite
      precipitates all clearly indicate that iron-meteorite-based chemolithotrophic
      metabolism is viable.

PMID- 15941384
TI  - Why O2 is required by complex life on habitable planets and the concept of
      planetary "oxygenation time".
AB  - Life is constructed from a limited toolkit: the Periodic Table. The reduction of
      oxygen provides the largest free energy release per electron transfer, except for
      the reduction of fluorine and chlorine. However, the bonding of O2 ensures that
      it is sufficiently stable to accumulate in a planetary atmosphere, whereas the
      more weakly bonded halogen gases are far too reactive ever to achieve significant
      abundance. Consequently, an atmosphere rich in O2 provides the largest feasible
      energy source. This universal uniqueness suggests that abundant O2 is necessary
      for the high-energy demands of complex life anywhere, i.e., for actively mobile
      organisms of approximately 10(-1)-10(0) m size scale with specialized,
      differentiated anatomy comparable to advanced metazoans. On Earth, aerobic
      metabolism provides about an order of magnitude more energy for a given intake of
      food than anaerobic metabolism. As a result, anaerobes do not grow beyond the
      complexity of uniseriate filaments of cells because of prohibitively low growth
      efficiencies in a food chain. The biomass cumulative number density, n, at a
      particular mass, m, scales as n (> m) proportional to m(-1) for aquatic aerobes,
      and we show that for anaerobes the predicted scaling is n proportional to m (
      1.5), close to a growth-limited threshold. Even with aerobic metabolism, the
      partial pressure of atmospheric O2 (P(O2)) must exceed approximately 10(3) Pa to
      allow organisms that rely on O2 diffusion to evolve to a size approximately 10(3)
      m x P(O2) in the range approximately 10(3)-10(4) Pa is needed to exceed the
      threshold of approximately 10(2) m size for complex life with circulatory
      physiology. In terrestrial life, O(2) also facilitates hundreds of metabolic
      pathways, including those that make specialized structural molecules found only
      in animals. The time scale to reach P(O(2)) approximately 10(4) Pa, or
      "oxygenation time," was long on the Earth (approximately 3.9 billion years),
      within almost a factor of 2 of the Sun's main sequence lifetime. Consequently, we
      argue that the oxygenation time is likely to be a key rate-limiting step in the
      evolution of complex life on other habitable planets. The oxygenation time could
      preclude complex life on Earth-like planets orbiting short-lived stars that end
      their main sequence lives before planetary oxygenation takes place. Conversely,
      Earth-like planets orbiting long-lived stars are potentially favorable habitats
      for complex life.

PMID- 15941386
TI  - The 5' flanking region of the Rhesus monkey H3 (DMBT1) gene contains putative
      progesterone response elements.
AB  - DMBT1 (deleted in malignant brain tumors) encodes a large scavenger receptor
      cysteine rich (SRCR) protein with proposed tumor suppressor properties due to its
      frequent deletion or lack of expression in a variety of different tumors
      including endometrial cancers. The gene is alternatively spliced to produce a
      number of related proteins with suspected functions in mucosal inflammation and
      epithelial regeneration. Expression of DMBT1 has been demonstrated in a wide
      variety of cell types, mostly of epithelial origin, including tissues of the
      respiratory system, the alimentary system, brain, and reproductive system. We
      have previously identified a Rhesus monkey cDNA clone H3 (homologous to human
      DMBT1) as a progesterone-induced gene in Rhesus monkey endometrium during the
      secretory phase of the menstrual cycle. As an initial step in understanding the
      molecular mechanisms of H3 (DMBT1) regulation we have cloned and sequenced 1.5 kb
      of the 5'-flanking region expected to contain promoter sequences of the Rhesus
      monkey gene and identified six putative progesterone receptor binding sites in
      the 5'-upstream region.

PMID- 15941387
TI  - HER2-mediated internalization of a targeted prodrug cytotoxic conjugate is
      dependent on the valency of the targeting ligand.
AB  - HER2 is a validated therapeutic target for cancer. There are no natural ligands,
      but monoclonal antibodies and peptides that bind HER2 act as artificial ligands,
      selectively affecting HER2-overexpressing tumors. One reported mechanism for this
      effect is receptor downregulation, but the expected correlation of ligand
      dependent HER2 internalization and tumor inhibition remain poorly characterized.
      Moreover, HER2 ligands have limited therapeutic efficacy and often they require
      adjuvant treatment with the chemotherapeutic Taxol. Here, we generated a series
      of HER2 ligands (Anti-HER2/neu peptide ligands, AHNPmonovalent and AHNPbivalent)
      with different valency and correlated their internalization-promoting ability to
      biological potency. Since AHNPbivalent (but not AHNPmonovalent) induces rapid
      receptor internalization, we exploited this feature to deliver cytotoxic
      conjugates coupling AHNPbivalent and Taxol (Taxol . AHNPbivalent). The prodrug
      conjugate releases Taxol after receptor-mediated internalization, and
      cytotoxicity can be used as a marker of internalization. Taxol . AHNPbivalent is
      significantly more cytotoxic than free Taxol + free AHNPbivalent. Hence, the
      Taxol x AHNP(bivalent) prodrug binds to HER2, induces receptor internalization
      and downregulation, and the subsequent release of free Taxol inside the targeted
      cell results in synergistic toxicity, The effect is selective towards HER2-
      expressing cells. This work links HER2 receptor internalization and growth
      arrest, and the chemical conjugation strategy may yield improved and HER2
      selective therapeutics.

PMID- 15941388
TI  - Correlation between alterations in nucleosomal organization of LINEs in the
      promoter of cytochrome P450 2B1/2 gene and induction of CYP 2B1/2B2 mRNA
      expression by phenobarbitone in rat liver.
AB  - Mammalian genome contains a high proportion of repetitive DNA with a sizeable
      fraction of Long Interspersed Nuclear Elements (LINEs). LINEs have been
      functionally implicated in the organization and evolution of mammalian genome.
      However, functions of LINEs in the promoter region and gene expression are poorly
      understood. Here, we report two small, conserved LINE sequences (3P and 5P) that
      occur as multiple copies of inverted repeats in the rat Cytochrome P450 2B1/2B2
      (CYP 2B1/2) gene promoter. Using 3P or 5P as a single primer, the CYP 2B1/2
      promoter DNA was amplified by PCR from the rat genome. Phenobarbitone (PB), a
      prototype xenobiotic drug, strongly induced CYP 2B1/2 mRNA expression in the rat
      liver. 3P and 5P LINE sequences showed an alteration in the nucleosomal
      organization in the CYP 2B1/2 promoter after 2, 4, and 6 h of PB induction, and
      the promoter was mostly devoid of nucleosomes during the induction.
      Reorganization of nucleosomes associated with these LINE sequences were strongly
      correlated with induction of CYP 2B1/2 mRNA expression by PB in vivo. Our results
      strongly suggest that these LINE sequences in CYP 2B1/2 gene promoter(s) may
      facilitate transcriptional activation of the gene(s) by PB through retention and
      reorganization of nucleosomes. This might be a novel function of LINEs in the
      mammalian genome that correlates the chromatin structure with gene expression
      during drug metabolism.

PMID- 15941389
TI  - Characterization of a novel class II bHLH transcription factor from the black
      widow spider, Latrodectus hesperus, with silk-gland restricted patterns of
      expression.
AB  - Members of the basic helix-loop-helix (bHLH) family are required for a number of
      different developmental pathways, including lymphopoiesis, myogenesis,
      neurogenesis, and sex determination. Screening a cDNA library prepared from silk
      producing glands of the black widow spider, we have identified a new bHLH
      transcription factor named SGSF. Within the bHLH region, SGSF showed considerable
      conservation with other HLH proteins, including Drosophila melanogaster achaete
      and scute, as well as three HLH proteins identified by gene prediction programs.
      The expression pattern of SGSF was restricted to a subset of silk-producing
      glands, which include the tubuliform and major ampullate glands. SGSF was capable
      of binding an E-box element as a heterodimer with the E protein, E47, but was
      unable to bind this motif as a homodimer. SGSF was demonstrated to be a nuclear
      transcription factor capable of attenuating the transactivation of E47 homodimers
      in mammalian cells. SGSF represents the first example of a silk gland-restricted
      bHLH protein, and its expression pattern suggests that SGSF plays a role in
      regulating differentiation of cells in the spider that control silk gland
      formation or egg case silk gene expression.

PMID- 15941390
TI  - Optimization of gene transfer into neonatal rat cardiomyocytes and unmasking of
      cytomegalovirus promoter silencing.
AB  - Cardiomyocytes are notoriously difficult to transfect using standard techniques
      unless viral vectors such as recombinant adenoviruses are used. Generation of
      recombinant adenoviruses is, however, a complex and time-consuming procedure and
      not possible for every DNA construct. We therefore optimized
      DNA/polylysine/adenovirus complexing for efficient gene transfer in neonatal rat
      cardiomyocytes determining the critical parameters for this method. Importantly,
      not only the concentration of the various components but also the method used for
      plasmid purification is critical for this transfection technique. Cesium-chloride
      purified DNA is inferior to anion-exchange methods for this purpose possibly
      because of altered ionic properties. In the second part of this study, we could
      demonstrate silent gene transfer into cardiomyocytes applying this optimized
      technique to plasmids encoding luciferase or beta-galactosidase cDNAs under the
      control of the cytomegalovirus immediate-early promoter. Phorbol myristate
      acetate and/or forskolin increased the amount of beta-galactosidase positive
      cells up to fivefold. Luciferase activity could even be increased as much as
      ninefold. These results demonstrate that the cytomegalovirus promoter is not
      maximally active in neonatal rat cardiomyocytes under basal conditions. In fact,
      a large proportion of cells is silently transfected and seems to express (an)
      inhibitor(s) of transcription from the CMV promoter that can be overcome by
      stimulation of cAMP- or protein kinase C-dependent pathways.

PMID- 15941391
TI  - Evidence for a role of vertebrate Rad52 in the repair of topoisomerase II
      mediated DNA damage.
AB  - DNA topoisomerase II (Top2) inhibitors are useful as anticancer agents, mostly by
      virtue of their ability to induce DNA double-strand breaks (DSBs). These DSBs are
      repaired almost exclusively by Rad52-dependent homologous recombination (HR) in
      yeast. However, we have recently shown that in vertebrate cells such lesions are
      primarily repaired by nonhomologous end-joining, but not HR. This finding, taken
      together with previous observations that disruption of RAD52 does not severely
      affect HR in vertebrate cells, makes it highly unlikely that Rad52 contributes to
      the repair of Top2-mediated DNA damage. However, in this paper we show that
      chicken cells lacking Rad52 do exhibit increased sensitivity to the Top2
      inhibitor VP-16. Remarkably, the level of hypersensitivity of RAD52-null cells
      was comparable to that of RAD54-null cells, albeit only at high doses. Our data
      thus provide the first demonstration of a major repair defect associated with
      loss of Rad52 in vertebrate cells.

PMID- 15941392
TI  - A Comparative study of Fe(II) and Fe(III) interactions with DNA duplex: major and
      minor grooves bindings.
AB  - The involvement of the Fe cations in autoxidation in cells and tissues is well
      documented. DNA is a major target in such reaction, and can chelate Fe cation in
      many ways. The present study was designed to examine the interaction of calf
      thymus DNA with Fe(II) and Fe(III), in aqueous solution at pH 6.5 with cation/DNA
      (P) (P = phosphate) molar ratios (r) of 1:160 to 1:2. Capillary electrophoresis
      and Fourier transform infrared (FTIR) difference spectroscopic methods were used
      to determine the cation binding site, the binding constant, helix stability and
      DNA conformation in Fe-DNA complexes. Structural analysis showed that at low
      cation concentration (r = 1/80 and 1/40), Fe(II) binds DNA through guanine N-7
      and the backbone PO(2) group with specific binding constants of K(G) = 5.40 x
      10(4) M(1) and K(P) = 2.40 x 10(4) M(1). At higher cation content, Fe(II)
      bindings to adenine N-7 and thymine O-2 are included. The Fe(III) cation shows
      stronger interaction with DNA bases and the backbone phosphate group. At low
      cation concentration (r = 1:80), Fe(III) binds mainly to the backbone phosphate
      group, while at higher metal ion content, cation binding to both guanine N-7 atom
      and the backbone phosphate group is prevailing with specific binding constants of
      K(G) = 1.36 x 10(5) M(-1) and K(P) = 5.50 x 10(4) M(-1). At r = 1:10, Fe(II)
      binding causes a minor helix destabilization, whereas Fe(III) induces DNA
      condensation. No major DNA conformational changes occurred upon iron complexation
      and DNA remains in the B-family structure.

PMID- 15941393
TI  - Analysis of sulfur and selenium assimilation in Astragalus plants with varying
      capacities to accumulate selenium.
AB  - Several Astragalus species have the ability to hyperaccumulate selenium (Se) when
      growing in their native habitat. Given that the biochemical properties of Se
      parallel those of sulfur (S), we examined the activity of key S assimilatory
      enzymes ATP sulfurylase (ATPS), APS reductase (APR), and serine acetyltransferase
      (SAT), as well as selenocysteine methyltransferase (SMT), in eight Astragalus
      species with varying abilities to accumulate Se. Se hyperaccumulation was found
      to positively correlate with shoot accumulation of S-methylcysteine (MeCys) and
      Se-methylselenocysteine (MeSeCys), in addition to the level of SMT enzymatic
      activity. However, no correlation was observed between Se hyperaccumulation and
      ATPS, APR, and SAT activities in shoot tissue. Transgenic Arabidopsis thaliana
      overexpressing both ATPS and APR had a significant enhancement of selenate
      reduction as a proportion of total Se, whereas SAT overexpression resulted in
      only a slight increase in selenate reduction to organic forms. In general, total
      Se accumulation in shoots was lower in the transgenic plants overexpressing ATPS,
      PaAPR, and SAT. Root growth was adversely affected by selenate treatment in both
      ATPS and SAT overexpressors and less so in the PaAPR transgenic plants. Such
      observations support our conclusions that ATPS and APR are major contributors of
      selenate reduction in planta. However, Se hyperaccumulation in Astragalus is not
      driven by an overall increase in the capacity of these enzymes, but rather by
      either an increased Se flux through the S assimilatory pathway, generated by the
      biosynthesis of the sink metabolites MeCys or MeSeCys, or through an as yet
      unidentified Se assimilation pathway.

PMID- 15941394
TI  - Identification of a putative voltage-gated Ca2+ channel as a key regulator of
      elicitor-induced hypersensitive cell death and mitogen-activated protein kinase
      activation in rice.
AB  - Elicitor-triggered transient membrane potential changes and Ca2+ influx through
      the plasma membrane are thought to be important during defense signaling in
      plants. However, the molecular bases for the Ca2+ influx and its regulation
      remain largely unknown. Here we tested effects of overexpression as well as
      retrotransposon (Tos17)-insertional mutagenesis of the rice two-pore channel 1
      (OsTPC1), a putative voltage-gated Ca(2+)-permeable channel, on a proteinaceous
      fungal elicitor-induced defense responses in rice cells. The overexpressor showed
      enhanced sensitivity to the elicitor to induce oxidative burst, activation of a
      mitogen-activated protein kinase (MAPK), OsMPK2, as well as hypersensitive cell
      death. On the contrary, a series of defense responses including the cell death
      and activation of the MAPK were severely suppressed in the insertional mutant,
      which was complemented by overexpression of the wild-type gene. These results
      suggest that the putative Ca(2+)-permeable channel determines sensitivity to the
      elicitor and plays a role as a key regulator of elicitor-induced defense
      responses, activation of MAPK cascade and hypersensitive cell death.

PMID- 15941395
TI  - The Medicago CDKC;1-CYCLINT;1 kinase complex phosphorylates the carboxy-terminal
      domain of RNA polymerase II and promotes transcription.
AB  - The Ms;CDKC;1 kinase is structurally similar to those cyclin-dependent kinases
      (CDKs) that are not involved directly in cell cycle regulation. The presence of a
      PITAIRE motif in Ms;CDKC;1 suggests that it interacts with cyclins different from
      known PSTAIRE/PPTALRE kinase regulatory subunits. Here we demonstrate that a
      Medicago CYCLINT (CYCT) protein is a specific interactor of Ms;CDKC;1 and the
      interaction between these two proteins gives rise to an active kinase complex
      that localizes to the nucleus and phosphorylates the carboxy-terminal YSPTSPS
      heptapeptide repeat domain (CTD) of the largest subunit of RNA polymerase II in
      vitro. Mutation of Ser to Ala at position 5 within the heptapeptide repeat
      abolishes substrate phosphorylation by the Ms;CDKC;1 kinase complex. Furthermore,
      our data show that addition of the Medicago CDKC;1-CYCT;1 heterodimer completely
      restored the transcriptional activity of a HeLa nuclear extract depleted of
      endogeneous CDK9 kinase complexes. Together, these results indicate that the
      Medicago CDKC;1-CYCT;1 complex is a positive regulator of transcription in plants
      and has a role similar to the CDK9/cyclin T complex of human positive
      transcription elongation factor P-TEFb.

PMID- 15941396
TI  - Calcium regulation of chloroplast protein import.
AB  - The majority of chloroplast proteins is nuclear-encoded and therefore synthesized
      on cytosolic ribosomes. In order to enter the chloroplast, these proteins have to
      cross the double-membrane surrounding the organelle. This is achieved by means of
      two hetero-oligomeric protein complexes in the outer and inner envelope, the Toc
      and Tic translocon. The process of chloroplast import is highly regulated on both
      sides of the envelope membranes. Our studies indicate the existence of an
      undescribed mode of control for this process so far, at the same time providing
      further evidence that the chloroplast is integrated into the calcium-signalling
      network of the cell. In pea chloroplasts, the calmodulin inhibitor Ophiobolin A
      as well as the calcium ionophores A23187 and Ionomycin affect the translocation
      of those chloroplast proteins that are imported with an N-terminal cleavable
      presequence. Import of these proteins is inhibited in a concentration-dependent
      manner. Addition of external calmodulin or calcium can counter the effect of
      these inhibitors. Translocation of chloroplast proteins that do not possess a
      cleavable transit peptide, that is outer envelope proteins or the inner envelope
      protein Tic32, is not affected. These results suggest that the import of a
      certain subset of chloroplast proteins is regulated by calcium. Our studies
      furthermore indicate that this regulation occurs downstream of the Toc translocon
      either within the intermembrane space or at the inner envelope translocon. A
      potential promoter of the calcium regulation is calmodulin, a protein well known
      as part of the plant's calcium signalling system.

PMID- 15941397
TI  - Identification and expression analysis of two inorganic C- and N-responsive genes
      encoding novel and distinct molecular forms of eukaryotic phosphoenolpyruvate
      carboxylase in the green microalga Chlamydomonas reinhardtii.
AB  - Phosphoenolpyruvate carboxylase (PEPC [Ppc]) has been previously purified and
      characterized in biochemical and immunological terms from two green microalgae,
      Chlamydomonas reinhardtii and Selenastrum minutum. The findings indicate that
      these algae possess at least two distinct PEPC enzyme-forms, homotetrameric Class
      1 and heteromeric Class-2, that differ significantly from each other and their
      plant and prokaryotic counterparts. Surprisingly, however, green-algal PEPC has
      been unexplored to date in molecular terms. This study reports the molecular
      cloning of the two Ppc genes in C. reinhardtii (CrPpc1, CrPpc2), each of which is
      transcribed in vivo and encodes a fully active, recombinant PEPC that lacks the
      regulatory, N-terminal seryl-phosphorylation domain that typifies the vascular
      plant enzyme. These distinct catalytic subunit-types differ with respect to their
      (i) predicted molecular mass ( approximately 108.9 [CrPpc1] versus approximately
      131.2 kDa [CrPpc2]) and critical C-terminal tetrapeptide; and (ii)
      immunoreactivity with antisera against the p102 and p130 polypeptides of S.
      minutum PEPC1/PEPC2 and PEPC2, respectively. Only the Ppc1 transcript encodes the
      p102 catalytic subunits common to both Class-1 and Class-2 enzyme-forms in C.
      reinhardtii. The steady-state transcript levels of both CrPpc1/2 are coordinately
      up-/down-regulated by changes in [CO2] or [NH] during growth, and generally
      mirror the response of cytoplasmic glutamine synthetase (Gs1) transcript
      abundance to changes in inorganic [N] at 5% CO2. These collective findings
      provide key molecular insight into the Ppc genes and corresponding PEPC catalytic
      subunits in the eukaryotic algae.

PMID- 15941398
TI  - Characterization of two GL8 paralogs reveals that the 3-ketoacyl reductase
      component of fatty acid elongase is essential for maize (Zea mays L.)
      development.
AB  - Prior analyses established that the maize (Zea mays L.) gl8a gene encodes 3
      ketoacyl reductase, a component of the fatty acid elongase required for the
      biosynthesis of very long chain fatty acids (VLCFAs). A paralogous gene, gl8b,
      has been identified that is 96% identical to gl8a. The gl8a and gl8b genes map to
      syntenic chromosomal regions, have similar, but not identical, expression
      patterns, and encode proteins that are 97% identical. Both of these genes are
      required for the normal accumulation of cuticular waxes on seedling leaves. The
      chemical composition of the cuticular waxes from gl8a and gl8b mutants indicates
      that these genes have at least overlapping, if not redundant, functions in
      cuticular wax biosynthesis. Although gl8a and gl8b double mutant kernels have
      endosperms that cannot be distinguished from wild-type siblings, these kernels
      are non-viable because their embryos fail to undergo normal development. Double
      mutant kernels accumulate substantially reduced levels of VLCFAs. VLCFAs are
      components of a variety of compounds, for example, cuticular waxes, suberin, and
      sphingolipids. Consistent with their essential nature in yeast, the accumulation
      of the ceramide moiety of sphingolipids is substantially reduced and their fatty
      acid composition altered in gl8a and gl8b double mutant kernels relative to wild
      type kernels. Hence, we hypothesize that sphingolipids or other VLCFA-containing
      compounds are essential for normal embryo development.

PMID- 15941399
TI  - The plant Mo-hydroxylases aldehyde oxidase and xanthine dehydrogenase have
      distinct reactive oxygen species signatures and are induced by drought and
      abscisic acid.
AB  - The plant molybdenum-cofactor (Moco) and flavin-containing enzymes, xanthine
      dehydrogenase (XDH; EC 1.2.1.37) and aldehyde oxidase (AO; EC 1.2.3.1) are
      thought to play important metabolic roles in purine metabolism and hormone
      biosynthesis, respectively. Their animal counterparts contribute to reactive
      oxygen species (ROS) production in numerous pathologies and here we examined
      these enzymes as potential sources of ROS in plants. Novel in-gel assay
      techniques and Moco sulfurase mutants, lacking a sulfur ligand in their Moco
      active center, were employed to demonstrate that the native tomato and
      Arabidopsis XDHs are capable of producing O, but not H2O2, while the animal
      counterpart was shown to produce both, O and H2O2. Superoxide production was
      dependent on Moco sulfuration when using hypoxanthine/xanthine but not NADH as
      substrates. The activity was inhibited by diphenylene iodonium (DPI), a suicide
      inhibitor of FAD containing enzymes. Analysis of XDH in an Arabidopsis Atxdh1 T
      DNA insertion mutant and RNA interference lines revealed loss of O activity,
      providing direct molecular evidence that plant XDH generates superoxides.
      Contrary to XDH, AO activity produced only H2O2 dissimilar to native animal AO,
      that can produce O as well. Surprisingly, H2O2 accumulation was not sensitive to
      DPI. Plant ROS production and transcript levels of AO and XDH were rapidly
      upregulated by application of abscisic acid and in water-stressed leaves and
      roots. These results, supported by in vivo measurement of ROS accumulation,
      indicate that plant AO and XDH are possible novel sources for ROS increase during
      water stress.

PMID- 15941400
TI  - Experimental determination of proline hydroxylation and hydroxyproline
      arabinogalactosylation motifs in secretory proteins.
AB  - Many secretory and several vacuolar proteins in higher plants contain
      hydroxylated proline residues. In many cases, hydroxyprolines in proteins are
      glycosylated with either arabinogalactan or oligoarabinose. We have previously
      shown that a sporamin precursor is O-glycosylated at the hydroxylated proline 36
      residue with an arabinogalactan-type glycan when this protein is expressed in
      tobacco BY-2 cells (Matsuoka et al., 1995). Taking advantage of the fact that
      this is the only site of proline hydroxylation and glycosylation in sporamin, we
      analyzed the amino acid requirement for proline hydroxylation and
      arabinogalactosylation. We expressed several deletion constructs and many amino
      acid substitution mutants in tobacco cells and analyzed glycosylation and proline
      hydroxylation of the expressed sporamins. Hydroxylation of a proline residue
      requires the five amino acid sequence [AVSTG]-Pro-[AVSTGA]-[GAVPSTC]-[APS or
      acidic] (where Pro is the modification site) and glycosylation of hydroxyproline
      (Hyp) requires the seven amino acid sequence [not basic]-[not T]-[neither P, T,
      nor amide]-Hyp-[neither amide nor P]-[not amide]-[APST], although charged amino
      acids at the -2 position and basic amide residues at the +1 position relative to
      the modification site seem to inhibit the elongation of the arabinogalactan side
      chain. Based on the combination of these two requirements, we concluded that the
      sequence motif for efficient arabinogalactosylation, including the elongation of
      the glycan side chain, is [not basic]-[not T]-[AVSG]-Pro-[AVST]-[GAVPSTC]-[APS].

PMID- 15941401
TI  - Cold-inducible zinc finger-containing glycine-rich RNA-binding protein
      contributes to the enhancement of freezing tolerance in Arabidopsis thaliana.
AB  - Glycine-rich RNA-binding proteins (GR-RBPs) have been implicated to play roles in
      post-transcriptional regulation of gene expression in plants under various stress
      conditions, but the functional roles of GR-RBPs under stress conditions remain to
      be verified. Here, we examine the biological roles of a GR-RBP, designated atRZ
      1a, in Arabidopsis thaliana under stress conditions. atRZ-1a was expressed
      ubiquitously in various Arabidopsis organs including stems, roots, leaves,
      flowers, and siliques. The transcript level of atRZ-1a increased markedly by cold
      stress, whereas its expression was marginally downregulated by drought stress or
      abscisic acid treatment. Germination and seedling growth of the loss-of-function
      mutants were retarded remarkably compared with those of the wild type under cold
      stress. In contrast, the transgenic Arabidopsis plants that overexpress atRZ-1a
      displayed earlier germination and better seedling growth than the wild type under
      cold stress. Moreover, the atRZ-1a-overexpressing transgenic Arabidopsis plants
      were more freezing tolerant than the wild-type plants. Heterologous expression of
      atRZ-1a in Escherichia coli demonstrated that the E. coli cells expressing atRZ
      1a displayed much higher growth rate than the non-transformed cells after cold
      shock. These results provide evidence that atRZ-1a affects seed germination and
      seedling growth under low temperature and plays a role in the enhancement of
      freezing tolerance in Arabidopsis plants.

PMID- 15941402
TI  - White-core endosperm floury endosperm-4 in rice is generated by knockout
      mutations in the C-type pyruvate orthophosphate dikinase gene (OsPPDKB).
AB  - We have isolated a floury endosperm-4 (flo4) rice mutant with a floury-white
      endosperm but a normal outer portion. Scanning electron microscopic analysis
      revealed that this abnormal endosperm consisted of loosely packed starch
      granules. The mutant phenotype was generated by T-DNA insertion into the fifth
      intron of the OsPPDKB gene encoding pyruvate orthophosphate dikinase (PPDK).
      Plants containing flo4-1 produced no OsPPDKB transcript or the OsPPDKB protein in
      their developing kernels and leaves. We obtained two additional alleles, flo4-2
      and flo4-3, that also showed the same white-core endosperm phenotype. The flo4
      kernels weighed about 6% less than wild-type ones. Starch contents in both kernel
      types were similar, but the total protein content was slightly higher in the
      mutant kernels. Moreover, lipid contents were significantly increased in the flo4
      kernels. Expression analyses demonstrated that the cytosolic mRNA of OsPPDKB was
      induced in the reproductive organs after pollination, and greatly increased until
      about 10 days after fertilization. This mRNA was localized mainly in the
      endosperm, aleurone, and scutellum of the developing kernel. Our results suggest
      that cytosolic PPDK functions in rice to modulate carbon metabolism during grain
      filling.

PMID- 15941403
TI  - The eukaryotic translation initiation factor 4E confers multiallelic recessive
      Bymovirus resistance in Hordeum vulgare (L.).
AB  - Virus diseases are widespread threats for crop production, which can, in many
      cases, be controlled efficiently by exploiting naturally occurring resistance.
      Barley, an important cereal species of the Triticeae, carries two genes, rym4 and
      rym5, which are located in the telomeric region of chromosome 3HL and confer
      recessive resistance to various strains of the Barley yellow mosaic virus
      complex. The barley 'eukaryotic translation initiation factor 4E' (Hv-eIF4E) was
      identified as a candidate for resistance gene function by physical mapping on a
      650 kb contig. It is located in a chromosomal region characterized by suppressed
      recombination, in a position collinear to its homologue on rice chromosome 1L.
      Sequence diversity in the coding region of Hv-eIF4E, as calculated from a
      collection of unrelated barley accessions, revealed non-silent single nucleotide
      polymorphisms (SNPs) in four of its five exons. Stable transformation of a
      resistant barley genotype with a genomic fragment or a full-length cDNA of Hv
      eIF4E derived from susceptible cultivars induced susceptibility to Barley mild
      mosaic virus. Moreover, the identification of SNPs diagnostic for rym4 and rym5
      provides evidence that these are two alleles, which confer different resistance
      specificities. These findings demonstrate that variants of Hv-eIF4E confer
      multiallelic recessive virus resistance in a monocot species. The identification
      of eIF4E as the causal host factor for bymovirus resistance illustrates that
      mutations in this basic component of the eukaryotic translation complex form a
      seminal mechanism for recessive virus resistance in both dicot and monocot
      plants.

PMID- 15941404
TI  - The cell biology of Hermansky-Pudlak syndrome: recent advances.
AB  - Hermansky-Pudlak syndrome (HPS) defines a group of at least seven autosomal
      recessive disorders characterized by albinism and prolonged bleeding. These
      manifestations arise from defects in the biogenesis of lysosome-related
      organelles, including melanosomes and platelet dense granules. Most genes
      associated with HPS in humans and rodent models of the disease encode components
      of multisubunit protein complexes that are expressed ubiquitously and play roles
      in intracellular protein trafficking and/or organelle distribution. A small
      GTPase of the Rab family, Rab38, is also implicated in the pathogenesis of the
      disease. This article reviews recent progress toward elucidating the cellular
      functions of these proteins.

PMID- 15941405
TI  - The CHiPS Domain--ancient traces for the Hermansky-Pudlak syndrome.
AB  - Hermansky-Pudlak syndrome (HPS) is a rare disorder caused by malfunctions of
      lysosomes and specialized lysosome-related organelles, resulting primarily in
      oculocutaneous albinism and bleeding diathesis. The majority of the HPS genes
      have been described as novel, but herein we report the identification of a
      conserved protein family which includes human HPS4, as well as distant homologs
      for other HPS genes. Our results suggest that the cellular machinery involved in
      the HPS syndrome is ancient.

PMID- 15941406
TI  - Analysis of the AP-2 adaptor complex and cargo during clathrin-mediated
      endocytosis.
AB  - Previously, we reported that the hetero-tetrameric adaptor complex AP-2 co
      localizes with the static population of clathrin spots, whereas it is excluded
      from clathrin spots that disappear from the plasma membrane (forming clathrin
      coated vesicles). More recently however, another group provided evidence that AP
      2 markers could be observed coincident with disappearing clathrin spots. Thus, we
      tested several possible explanations for the apparent discrepancies in these two
      studies. We evaluated the potential contribution of nonred emission of clathrin
      dsRed (used in both studies) in the simultaneous measurement of AP-2 and clathrin
      at various times. Additionally, we directly compared two different green
      fluorescent protein-tagged AP-2 constructs (similar to those used in the previous
      reports). These studies demonstrated that the duration of expression time greatly
      influences the subcellular localization of the AP-2 markers. Furthermore, we
      quantitatively evaluated the AP-2 fluorescence at the sites of numerous static
      and disappearing clathrin spots (at least 80 per group) and confirmed our initial
      observation that while AP-2 is present in nearly all static clathrin spots, it is
      excluded from the disappearing population of clathrin spots. Finally, in order to
      verify that clathrin spot disappearance represents clathrin-coated vesicle
      internalization, we simultaneously imaged clathrin and the cargo molecule
      transferrin at the cell surface.

PMID- 15941407
TI  - Brefeldin a inhibits circadian remodeling of chloroplast structure in the
      dinoflagellate gonyaulax.
AB  - Circadian increases in the rate of carbon fixation in the dinoflagellate
      Gonyaulax are correlated with extensive plastid remodeling. One marker for this
      remodeling is mobilization of ribulose bisphosphate carboxylase/oxygenase
      (Rubisco) from the plastid periphery to plastid regions nearer the cell center
      called pyrenoids. Nuclear-encoded proteins such as Rubisco transit through the
      Golgi in dinoflagellates; hence, we blocked protein import into the plastids
      using Brefeldin A (BFA) to explore the mechanism for plastid remodeling. We find
      that pyrenoid formation normally occurs concurrently with increased Rubisco
      synthesis rates in vivo, and when BFA is given prior to the onset of Rubisco
      synthesis, pyrenoid formation is partially or completely inhibited by 0.1 or 0.3
      microg/mL BFA, respectively. Rubisco synthesis itself is not affected, and BFA
      treated cells accumulate Rubisco in novel structures we term BFA bodies.
      Interestingly, when given just after the onset of Rubisco synthesis, BFA delays
      but does not block Rubisco mobilization, suggesting that a timing signal for
      plastid remodeling is delivered to the organelles at the same time as newly
      synthesized Rubisco. BFA also inhibits the circadian increases in carbon fixation
      rates, supporting the hypothesis that the biochemical basis for this circadian
      rhythm may be Rubisco distribution within the plastid.

PMID- 15941408
TI  - Endoplasmic reticulum exit of a secretory glycoprotein in the absence of sec24p
      family proteins in yeast.
AB  - Glycoproteins exit the endoplasmic reticulum (ER) of the yeast Saccharomyces
      cerevisiae in coat protein complex II (COPII) coated vesicles. The coat consists
      of the essential proteins Sec23p, Sec24p, Sec13p, Sec31p, Sar1p and Sec16p.
      Sec24p and its two nonessential homologues Sfb2p and Sfb3p have been suggested to
      serve in cargo selection. Using temperature-sensitive sec24-1 mutants, we showed
      previously that a secretory glycoprotein, Hsp150, does not require functional
      Sec24p for ER exit. Deletion of SFB2, SFB3 or both from wild type or the deletion
      of SFB2 from sec24-1 cells did not affect Hsp150 transport. SFB3 deletion has
      been reported to be lethal in sec24-1. However, here we constructed a sec24-1
      Deltasfb3 and a sec24-1 Deltasfb2 Deltasfb3 strain and show that Hsp150 was
      secreted slowly in both. Turning off the SEC24 gene did not inhibit Hsp150
      secretion either, and the lack of SEC24 expression in a Deltasfb2 Deltasfb3
      deletant still allowed some secretion. The sec24-1 Deltasfb2 Deltasfb3 mutant
      grew slower than sec24-1. The cells were irregularly shaped, budded from random
      sites and contained proliferated ER at permissive temperature. At restrictive
      temperature, the ER formed carmellae-like proliferations. Our data indicate that
      ER exit may occur in vesicles lacking a full complement of Sec23p/24p and
      Sec13p/31p, demonstrating diversity in the composition of the COPII coat.

PMID- 15941409
TI  - Verprolin cytokinesis function mediated by the Hof one trap domain.
AB  - In budding yeast, partitioning of the cytoplasm during cytokinesis can proceed
      via a pathway dependent on the contractile actomyosin ring, as in other
      eukaryotes, or alternatively via a septum deposition pathway dependent on an SH3
      domain protein, Hof1/Cyk2 (the yeast PSTPIP1 ortholog). In dividing yeast cells,
      Hof1 forms a ring at the bud neck distinct from the actomyosin ring, and this
      zone is active in septum deposition. We previously showed the yeast Wiskott
      Aldrich syndrome protein (WASP)-interacting protein (WIP) ortholog,
      verprolin/Vrp1/End5, interacts with Hof1 and facilitates Hof1 recruitment to the
      bud neck. A Vrp1 fragment unable to interact with yeast WASP (Las17/Bee1),
      localize to the actin cytoskeleton or function in polarization of the cortical
      actin cytoskeleton nevertheless retains function in Hof1 recruitment and
      cytokinesis. Here, we show the ability of this Vrp1 fragment to bind the Hof1 SH3
      domain via its Hof one trap (HOT) domain is critical for cytokinesis. The Vrp1
      HOT domain consists of three tandem proline-rich motifs flanked by serines.
      Unexpectedly, the Hof1 SH3 domain itself is not required for cytokinesis and
      indeed appears to negatively regulate cytokinesis. The Vrp1 HOT domain promotes
      cytokinesis by binding to the Hof1 SH3 domain and counteracting its inhibitory
      effect.

PMID- 15941410
TI  - Translocation biosensors to study signal-specific nucleo-cytoplasmic transport,
      protease activity and protein-protein interactions.
AB  - Regulated nucleo-cytoplasmic transport is crucial for cellular homeostasis and
      relies on protein interaction networks. In addition, the spatial division into
      the nucleus and the cytoplasm marks two intracellular compartments that can
      easily be distinguished by microscopy. Consequently, combining the rules for
      regulated nucleo-cytoplasmic transport with autofluorescent proteins, we
      developed novel cellular biosensors composed of glutathione S-transferase,
      mutants of green fluorescent protein and rational combinations of nuclear import
      and export signals. Addition of regulatory sequences resulted in three classes of
      biosensors applicable for the identification of signal-specific nuclear export
      and import inhibitors, small molecules that interfere with protease activity and
      compounds that prevent specific protein-protein interactions in living cells. As
      a unique feature, our system exploits nuclear accumulation of the cytoplasmic
      biosensors as the reliable readout for all assays. Efficacy of the biosensors was
      systematically investigated and also demonstrated by using a fully automated
      platform for high throughput screening (HTS) microscopy and assay analysis. The
      introduced modular biosensors not only have the potential to further dissect
      nucleo-cytoplasmic transport pathways but also to be employed in numerous
      screening applications for the early stage evaluation of potential drug
      candidates.

PMID- 15941411
TI  - The Gambian pneumococcal vaccine trial - implications for control of childhood
      pneumonia.

PMID- 15941412
TI  - The phenothiazinium chromophore and the evolution of antimalarial drugs.
AB  - The phenothiazinium salt methylene blue [3,7-bis(dimethylamino)phenothiazinium
      chloride] is the oldest known synthetic antimalarial drug, its clinical efficacy
      having been reported in 1891. The role of methylene blue in the evolution of the
      modern antimalarial armoury is often unappreciated, yet it can be linked directly
      to standard drugs such as chloroquine and its congeners. Also, in the face of
      increasing plasmodial resistance to modern antimalarials, phenothiazinium
      derivatives have again featured as lead compounds in drug research. The precise
      mode of action of methylene blue and its commercial analogues against Plasmodium
      spp. remains a cause for conjecture, having been variously described as nucleic
      acid intercalation, food vacuole basification, parasite redox cycle interference
      and haem polymerization inhibition. That the activity of the series may be due to
      more than one route - i.e. a multifactorial activity - underlines the utility of
      these compounds in antimalarial research either as single drugs or as adjuvants
      (partners in a drug combination), particularly in the face of resistant parasitic
      strains.

PMID- 15941413
TI  - A randomized, placebo-controlled, double-blind trial on sulfadoxine-pyrimethamine
      alone or combined with artesunate or amodiaquine in uncomplicated malaria.
AB  - The therapeutic efficacy of sulfadoxine-pyrimethamine (SP) alone, SP plus
      amodiaquine (AQ), and SP plus artesunate (AS) was assessed in a randomized,
      placebo-controlled, and double-blind trial among 438 children with uncomplicated
      Plasmodium falciparum malaria in northern Ghana. Clinical and parasitological
      responses were monitored for 28 days following treatment; 86%, 98% and 97% of SP
      , SP + AQ-, and SP + AS-treated patients achieved adequate clinical and
      parasitological response (ACPR) within 2 weeks, respectively. Parasite clearance
      was better with SP + AS than with SP or SP + AQ treatment but re-infections were
      more common. Polymerase chain reaction (PCR)-corrected rates of ACPR at day 28
      were 72.2% for SP, 94.1% for SP + AQ (P < 0.0001), and 94.5% for SP + AS (P <
      0.0001). Gametocyte prevalence and density 1 week after treatment were highest in
      children treated with SP, and lowest in patients receiving SP + AS. No severe
      adverse events attributable to study medication were observed. In northern Ghana,
      more than one of four children suffered SP treatment failure within 4 weeks. Both
      SP + AQ and SP + AS are efficacious alternative therapeutic options in this
      region. Although SP + AS and SP + AQ treatments have virtually identical cure
      rates, rapid parasite clearance and pronounced gametocidal effects are the
      advantages of the former, whereas cost and a lower rate of late re-infections are
      those of the latter.

PMID- 15941414
TI  - Efficacy of combination therapy with artesunate plus amodiaquine compared to
      monotherapy with chloroquine, amodiaquine or sulfadoxine-pyrimethamine for
      treatment of uncomplicated Plasmodium falciparum in Afghanistan.
AB  - INTRODUCTION: In South and Central Asia resistance to chloroquine (CQ) has
      reached unmanageable levels, and resistance to sulfadoxine-pyrimethamine (SP) is
      emerging. Amodiaquine (AQ) is widely used in the region, and elsewhere shows only
      partial resistance to CQ. In Afghanistan, one option for slowing the spread of
      resistance and improving treatment outcomes is the use of artemisinin combination
      therapy (ACT). METHODS: The efficacy of CQ, AQ, SP and amodiaquine plus
      artesunate (AQ/AS) in the treatment of uncomplicated falciparum malaria was
      investigated using standard World Health Organization (WHO) procedures. Malaria
      patients were randomized to four treatment groups: 268 were enrolled and 240
      completed the trial. RESULTS: There was a high level of cross-resistance between
      CQ and AQ resistance: adequate clinical and parasitological response by day 42
      was 11% after CQ treatment and 9% after AQ treatment. The trend of treatment
      failure between AQ and CQ was almost identical. Cure rates were considerably
      improved by the addition of artesunate to AQ or by use of SP; adequate clinical
      and parasitological response being 72% for AQ/AS and 92% for SP. The combination
      of AS/AQ substantially reduced the odds of treatment failure relative to AQ
      monotherapy by day 42 [odds ratio (OR) = 0.03, 95% confidence interval (CI) 0.01
      0.1] in addition to reducing the proportion of patients with gametocytes
      throughout the 42-day period. Gametocyte carriage rate was only marginally higher
      in the SP than in the CQ- and AQ-treated groups. CONCLUSION: The therapeutic and
      parasitological cure rates with AS/AQ were inadequate, and the criteria for
      deploying ACT - namely to prevent further selection of drug resistance from a
      position of low frequency - was not met in the region. An alternative drug
      combination to AQ/AS is required for Afghanistan.

PMID- 15941415
TI  - Clinical algorithms for malaria diagnosis lack utility among people of different
      age groups.
AB  - We conducted a study to determine whether clinical algorithms would be useful in
      malaria diagnosis among people living in an area of moderate malaria transmission
      within Kilifi District in Kenya. A total of 1602 people of all age groups
      participated. We took smears and recorded clinical signs and symptoms (prompted
      or spontaneous) of all those presenting to the study clinic with a history of
      fever. A malaria case was defined as a person presenting to the clinic with a
      history of fever and concurrent parasitaemia. A set of clinical signs and
      symptoms (algorithms) with the highest sensitivity and specificity for diagnosing
      a malaria case was selected for the age groups </=5 years, 6-14 years and >/=15
      years. These age-optimized derived algorithms were able to identify about 66% of
      the cases among those <15 years of age but only 23% of cases among adults. Were
      these algorithms to be used as a basis for a decision on treatment among those
      presenting to the clinic, 16% of children </=5 years, 44% of those 6-14 years of
      age and 66% of the adults who had a history of fever and parasitaemia >/=5000
      parasites/microl of blood would be sent home without treatment. Clinical
      algorithms therefore appear to have little utility in malaria diagnosis,
      performing even worse in the older age groups, where avoiding unnecessary use of
      anti-malarials would make more drugs available to the really needy population of
      children under 5 years of age.

PMID- 15941416
TI  - Plasmodium falciparum: higher incidence of molecular resistance markers for
      sulphadoxine than for pyrimethamine in Kasangati, Uganda.
AB  - In November of 2000, Uganda changed its anti-malarial policy to replace
      chloroquine (CQ) with a combination of CQ and sulphadoxine-pyrimethamine (SP) as
      the first line agents. Information was limited on the efficacy of either drug.
      The present study was designed to provide baseline information on the efficacy of
      SP and the prevalence of molecular markers that are associated with SP
      resistance. Blood samples were collected on filter paper from 169 consenting
      patients who were diagnosed with malaria. Patients were treated with SP and
      followed for 14 days using the WHO clinical guidelines. The samples were analysed
      for molecular resistance markers and correlation of the molecular markers with
      clinical findings was assessed. SP monotherapy was efficacious for 140 of 163
      (85.9%) treated patients. We found a high level of mutations in alleles which
      have previously been reported to be associated with SP resistance, but there was
      no correlation between clinical outcomes and molecular markers. With the
      exception of codon S108 in dhfr (dhfr S108N was at 94.9%), frequencies of
      dihydropteroate synthase (dhps) mutant and mixed alleles combined (A437G 89% and
      K540E 83.9%) were higher than those of dihydrofolate reductase (dhfr) (N51I
      58.4%, C59R 31.3%).

PMID- 15941417
TI  - Associations between frequencies of a susceptible TNF-alpha promoter allele and
      protective alpha-thalassaemias and malaria parasite incidence in Vanuatu.
AB  - Tumour necrosis factor-alpha (TNF-alpha) is one of the key cytokines that
      influence the pathology of microbial infections. The genetic susceptibility to
      severe forms of falciparum malaria is differentially associated with TNF-alpha
      promoter gene polymorphisms (TNFP alleles). In a previous study, we identified a
      TNFP-allele characterized by a C to T transition at position -857 (TNFP-D allele)
      as a marker for susceptibility to cerebral malaria in Myanmar. The frequencies of
      TNFP alleles on six islands of Vanuatu, Melanesia (South-west Pacific) were
      estimated to investigate whether malaria selection pressure on this
      susceptibility marker has influenced its prevalence. Within the archipelago of
      Vanuatu there is a decreasing cline of parasite incidence from North to South. Of
      the four alleles of the TNFP gene detected in Vanuatu, the TNFP-D allele
      frequencies were inversely correlated with the parasite incidence of islands;
      TNFP-D varied from 0.55 on the island with the lowest parasite incidence to 0.26
      on the island with the highest parasite incidence (r = -0.855, P = 0.03). We also
      observed a significant correlation between the frequencies of alpha-thalassaemia
      alleles, thought to protect against malaria and parasite incidence in the same
      populations. These data are consistent with a previously reported correspondence
      between the frequencies of glucose 6-phosphate dehydrogenase (G6PD) deficiency
      and parasite incidences on the islands of Vanuatu (Kaneko et al. 1998) and
      indicate that the degree of malaria endemicity has influenced the allele
      frequencies of at least three loci that confer both susceptibility (TNFP-D) and
      protection (alpha-thalassaemias and G6PD deficiency).

PMID- 15941418
TI  - Season, fever prevalence and pyrogenic threshold for malaria disease definition
      in an endemic area of Mali.
AB  - BACKGROUND: Modelling malaria parasitaemia as function of fever has been proposed
      as best alternative to estimate the attributable fraction of malaria fever and
      the sensitivity and specificity of different case definitions of malaria disease.
      OBJECTIVES: To determine the prevalence of fever and its relation to malaria
      parasitaemia and to establish a pyrogenic threshold for malaria disease in the
      area. METHODS: We conducted two cross-sectional surveys in children of 6 months
      to 9 years of age (2434 during the rainy season of 1993 and 2353 during the dry
      season of 1994) randomly selected from 21 areas of Bandiagara district, Mali.
      RESULTS: The relationship between fever and Plasmodium falciparum parasitaemia
      depends strongly on the season, thus affecting the malaria-attributable fraction
      of fever cases and the sensitivity and specificity of malaria case definitions.
      The overall proportion of fever attributable to malaria parasitaemia was 33.6%
      during the rainy season and 23.3% during the dry season, with the highest
      proportion occurring among the youngest children. The cut-off value, where the
      sensitivity curve crosses the specificity curve, was around 3200 pf/microl for
      all age categories during the rainy season and 200 pf/microl during the dry
      season. CONCLUSIONS: Malaria remains a main cause of fever in this area of Mali.
      The pyrogenic threshold of parasitaemia depends strongly on the season, and
      different cut-off levels of parasitaemia should be used during the two seasons to
      define malaria cases in this area.

PMID- 15941419
TI  - Modelling malaria risk in East Africa at high-spatial resolution.
AB  - OBJECTIVES: Malaria risk maps have re-emerged as an important tool for
      appropriately targeting the limited resources available for malaria control. In
      Sub-Saharan Africa empirically derived maps using standardized criteria are few
      and this paper considers the development of a model of malaria risk for East
      Africa. METHODS: Statistical techniques were applied to high spatial resolution
      remotely sensed, human settlement and land-use data to predict the intensity of
      malaria transmission as defined according to the childhood parasite ratio (PR) in
      East Africa. Discriminant analysis was used to train environmental and human
      settlement predictor variables to distinguish between four classes of PR risk
      shown to relate to disease outcomes in the region. RESULTS: Independent empirical
      estimates of the PR were identified from Kenya, Tanzania and Uganda (n = 330).
      Surrogate markers of climate recorded on-board earth orbiting satellites,
      population settlement, elevation and water bodies all contributed significantly
      to the predictive models of malaria transmission intensity in the sub-region. The
      accuracy of the model was increased by stratifying East Africa into two
      ecological zones. In addition, the inclusion of urbanization as a predictor of
      malaria prevalence, whilst reducing formal accuracy statistics, nevertheless
      improved the consistency of the predictive map with expert opinion malaria maps.
      The overall accuracy achieved with ecological zone and urban stratification was
      62% with surrogates of precipitation and temperature being among the most
      discriminating predictors of the PR. CONCLUSIONS: It is possible to achieve a
      high degree of predictive accuracy for Plasmodium falciparum parasite prevalence
      in East Africa using high-spatial resolution environmental data. However,
      discrepancies were evident from mapped outputs from the models which were largely
      due to poor coverage of malaria training data and the comparable spatial
      resolution of predictor data. These deficiencies will only be addressed by more
      random, intensive small areas studies of empirical estimates of PR.

PMID- 15941420
TI  - Physical and psychosocial burden due to lymphatic filariasis as perceived by
      patients and medical experts.
AB  - Patients with lymphatic filariasis (LF) face considerable physical, psychological
      and social disabilities. Morbidity management and control are important
      components of the Global Programme to Eliminate Lymphatic Filariasis. But
      information on the various disabilities caused by LF is scanty. We measured the
      severity levels of seven health states of LF in the physical and psychosocial
      domains of health from the perspective of patients and medical experts, using a 7
      domain 5-level (7D5L) descriptive system. Adenolymphangitis had the highest
      severity levels in all domains of health followed by lymphoedema grade 4 (L4),
      lymphoedema grade 3 (L3), hydrocele grade 2 (H2), lymphoedema grade 2 (L2),
      lymphoedema grade1 (L1) and hydrocele grade 1 (H1). People with higher grades of
      lymphoedema and hydrocele had more severe psychosocial problems than physical
      ones. Severity levels assessed by medical experts were lower than those reported
      by sufferers. These findings indicate that LF has considerable impact on the
      physical, mental and social domains of health. Morbidity management programmes
      should be broadened to include counselling, rehabilitation and health education
      to manage the psychosocial problems caused by LF.

PMID- 15941421
TI  - Polymerase chain reaction-based differential diagnosis of Ancylostoma duodenale
      and Necator americanus infections in humans in northern Ghana.
AB  - We evaluated a two-step semi-nested polymerase chain reaction (PCR)-based
      approach for the specific detection of Ancylostoma duodenale DNA in human faeces.
      The test was used to determine to what extent this species of hookworm is present
      in the regions of Bolgatanga and Garu of northern Ghana. Initially, the
      sensitivity and specificity of the PCR were tested using a range of well-defined
      control samples. Subsequently, a total of 378 human faecal DNA samples from
      Bolgatanga and Garu were subjected to the PCR. The results were compared with
      those obtained using a previously established PCR for the specific detection of
      Necator americanus DNA in human faeces. Infection with A. duodenale was recorded
      in 74 (19.6%) samples and N. americanus in 278 (73.5%), of which 64 (16.9%),
      represented co-infections with both species. While A. duodenale was predominantly
      detected in the samples from Bolgatanga, infections in Garu related almost
      exclusively to N. americanus. The results showed that the present PCR approach is
      a valuable complementary tool for the diagnosis of A. duodenale infection in
      humans in Ghana, having implications for epidemiological studies and for the
      monitoring of the success of control programmes in regions in Africa.

PMID- 15941422
TI  - Pesticide poisoning in south India: opportunities for prevention and improved
      medical management.
AB  - OBJECTIVE: Warangal district in Andhra Pradesh, southern India, records >1000
      pesticide poisoning cases each year and hundreds of deaths. We aimed to describe
      their frequency and distribution, and to assess quality of management and
      subsequent outcomes from pesticide poisoning in one large hospital in the
      district. METHODS: We reviewed data on all patients admitted with pesticide
      poisoning to a district government hospital for the years 1997 to 2002. For 2002,
      details of the particular pesticide ingested and management were abstracted from
      the medical files. FINDINGS: During these 6 years, 8040 patients were admitted to
      the hospital with pesticide poisoning. The overall case fatality ratio was 22.6%.
      More detailed data from 2002 revealed that two-thirds of the patients were <30
      years old, 57% were male and 96% had intentionally poisoned themselves. Two
      compounds, monocrotophos and endosulfan, accounted for the majority of deaths
      with known pesticides in 2002. Low fixed-dose regimens were used in the majority
      of cases for the most commonly used antidotes (atropine and pralidoxime).
      Inappropriate antidotes were also used in some patients. CONCLUSIONS: It is
      likely that these findings reflect the situation in many rural hospitals of the
      Asia Pacific region. Even without an increase in resources, there appear to be
      significant opportunities for reducing mortality by better medical management and
      further restrictions on the most toxic pesticides.

PMID- 15941423
TI  - Risk factors for acute pesticide poisoning in Sri Lanka.
AB  - This report describes the characteristics of patients with acute pesticide
      poisoning in a rural area of Sri Lanka and, for intentional self-poisoning cases,
      explores the relative importance of the different determinants. Data were
      collected for 239 acute pesticide-poisoning cases, which were admitted to two
      rural hospitals in Sri Lanka. Sociodemographic characteristics, negative life
      events and agricultural practices of the intentional self-poisoning cases were
      compared with a control group. Most cases occurred among young adults and the
      large majority (84%) was because of intentional self-poisoning. Case fatality was
      18% with extremely high case fatality for poisoning with the insecticide
      endosulfan and the herbicide paraquat. Cases were generally younger than
      controls, of lower educational status and were more often unemployed. No
      agricultural risk factors were found but a family history of pesticide poisoning
      and having ended an emotional relationship in the past year was clearly
      associated with intentional self-poisoning. The presence of mental disorders
      could only be assessed for a subsample of the cases and controls and this showed
      that alcohol dependence was a risk factor. This study shows that acute pesticide
      poisoning in Sri Lanka is determined by a combination of sociodemographic and
      psychological factors. Suggestions are given for interventions that could control
      the morbidity and mortality due to acute pesticide poisoning in developing
      countries.

PMID- 15941424
TI  - The Buen Pastor cemetery in Trujillo, Venezuela: measuring dengue vector output
      from a public area.
AB  - As vector control of dengue typically targets individual households to eliminate
      breeding sites or control adult mosquitoes during epidemics, public spaces are
      frequently neglected. To investigate the importance of such places as sources of
      dengue vectors, a study of Aedes aegypti productivity in a cemetery in northern
      Venezuela, using standard entomological indices for assessing dengue vector
      infestations, was carried out in the wet season in May 2003. Containers were
      found on 72.8% of graves; 44% of the containers held water and in 46.9% of these
      we found A. aegypti larvae and/or pupae. The average density of Aedes-infested
      containers was 39 per hectare. There were no significant differences in
      infestation rates between container types (vases, planters or others) or
      materials (cement, plastic, glass, etc.). Containers with 1-5 l of water held the
      greatest proportion of the pupae found in the cemetery (46.7%); containers with
      <100 ml of water contained no pupae. The mean number of pupae produced in the
      cemetery was estimated at 4185 pupae/ha per 48 h and the daily output of
      potential vector mosquitoes from the entire cemetery was calculated at
      approximately 3000 females per day. These mosquitoes presumably left the cemetery
      to feed in the nearby communities, thus thwarting the environmental management
      and health education programmes that had reduced household dengue vector
      infestations. The study shows the importance of public places as sources of
      dengue vectors in urban areas, and the need to include such areas in vector
      control programmes.

PMID- 15941425
TI  - Molecular tracking of the lineage of strains of Vibrio cholerae O1 biotype El Tor
      associated with a cholera outbreak in Andaman and Nicobar Islands, India.
AB  - A large outbreak of acute watery diarrhoea involving all age groups of mongoloid
      tribal aborigines occurred during October-November, 2002 in the Nancowry group of
      Andaman and Nicobar Islands in the Indian Ocean. Twenty-one of the 67 stool
      samples from 67 patients were positive for toxigenic Vibrio cholerae O1, serotype
      Ogawa biotype El Tor, which showed striking similarity in its antibiogram with
      some of the strains of V. cholerae O1 Serotype Ogawa biotype El Tor isolated in
      Kolkata. The Nancowry and Kolkata isolates were compared with molecular tools
      involving random amplified polymorphic DNA (RAPD) fingerprinting, ribotyping and
      pulsed-field gel electrophoresis (PFGE). RAPD fingerprinting and ribotyping
      techniques revealed that all the V. cholerae strains associated with the outbreak
      in these islands were clonal in nature and identical to a population of isolates
      obtained from Kolkata since 1993. PFGE could discriminate within these Kolkata
      isolates further and established that a particular subtype of this population
      reached the remote Nancowry islands and was responsible for the outbreak.

PMID- 15941426
TI  - Seroprevalence of Q-fever in febrile individuals in Mali.
AB  - OBJECTIVES: We conducted a serological survey for Q-fever among febrile patients
      in Bamako and Mopti (Mali) and investigated the main risk factors for
      seroconversion. METHODS: Blood samples from 156 febrile patients were collected
      in healthcare facilities of Bamako and Mopti and examined with the
      microimmunofluorescence test. RESULTS: Forty per cent (n = 63) were seropositive
      for Q-fever, 28% in Bamako and 51% in Mopti. A more recent infection was
      suspected in 9.5% (n = 6) of all seropositive patients. This is the first time
      that Q-fever seropositivity is reported in febrile individuals in Mali. The
      patients' symptoms and diagnoses spanned a wide range of conditions; none had
      been diagnosed with Q fever by their treating physician. No risk factors for
      seropositivity could be identified with the exception of the city of residence
      and none could be identified with a logistic regression model with 'city' taken
      as random effect. CONCLUSION: A high rate of seropositivity to C. burnetii was
      found among febrile urban patients in Mali but no risk factors for seropositivity
      could be identified in this study.

PMID- 15941427
TI  - Palestinian infantile visceral leishmaniasis caused by a genetic variant of
      Leishmania infantum belonging to a new zymodeme.
AB  - The parasites causing a Palestinian case of infantile visceral leishmaniasis
      (IVL) and those from four dogs from the Jenin District were identified
      serologically, biochemically and molecular biologically as Leishmania infantum,
      showing dogs act as a reservoir. The strain from the human case was distinct
      because of its unique 200-bp kDNA-polymerase chain reaction (PCR) component in
      its restriction fragment length polymorphism (RFLP) profile after digestion with
      the endonuclease RsaI, and by the electrophoretic mobility of its malate
      dehydrogenase (MDH(140)), designating it the reference strain of a new zymodeme
      of L. infantum, MON-281.

PMID- 15941428
TI  - Artemisinin-based combination treatment in home-based management of malaria.

PMID- 15941429
TI  - Infectious complications of tumor necrosis factor-alpha antagonists.

PMID- 15941430
TI  - Venous ulcer: epidemiology, physiopathology, diagnosis and treatment.
AB  - This review discusses the epidemiology, pathogenesis, diagnosis and current
      therapeutic options for venous ulcer. Venous ulcer is a severe clinical
      manifestation of chronic venous insufficiency (CVI). It is responsible for about
      70% of chronic ulcers of the lower limbs. The high prevalence of venous ulcer has
      a significant socioeconomic impact in terms of medical care, days off work and
      reduced quality of life. Long-term therapeutics are needed to heal venous ulcers
      and recurrence is quite common, ranging from 54 to 78%. Thrombophlebitis and
      trauma with long-term immobilization predisposing to deep venous thrombosis are
      important risk factors for CVI and venous ulcer. The most recent theories about
      pathogenesis of venous ulcer have associated it with microcirculatory
      abnormalities and generation of an inflammatory response. Management of venous
      leg ulcers is based on understanding the pathogenesis. In recent years novel
      therapeutic approaches for venous ulcers have offered valuable tools for the
      management of patients with this disorder.

PMID- 15941431
TI  - Thyroid autoimmunity in children and adolescents with alopecia areata.
AB  - BACKGROUND: Autoimmune thyroiditis (AT) is often associated with alopecia areata
      (AA) in children and adolescents. METHODS: Forty-six children (23 girls and 23
      boys), with a mean age of 9.9 +/- 3.38 years (2.24-17.5 years), were included in
      a study to assess thyroid function and thyroid autoantibody formation in AA. The
      size and function of the thyroid gland [triiodothyronine (T3), thyroxine (T4),
      thyroid-stimulating hormone (TSH), and thyrotropin releasing hormone (TRH) test;
      fluoroimmunologic assay (FIA), Delfia], antithyroglobulin (TAT) and
      antimicrosomal (MAT) antibodies (microhemagglutination method), thyroid gland
      ultrasound, and indices of cellular and humoral immunity were assessed. RESULTS:
      Thyromegaly was found in 29 children (63%). Increased basal TSH levels were
      present in six of the 29 (13.3%) and hypothyroid-type stimulated secretion (TRH
      test) in two (out of 12). TAT was increased in 17 (39.5%) and MAT in 14 (33.3%)
      children with AA. Thyroid ultrasound examination was suggestive of AT in 13
      (34.2%) and typical of AT in five (13.2%) children. CONCLUSIONS: We diagnosed AT
      in 22 of 46 children with AA (47.8%). The immune studies revealed increased
      activated T lymphocytes. We recommend that thyroid gland size and function and
      antibody formation be examined at the diagnosis of AA and twice a year
      thereafter.

PMID- 15941432
TI  - Development of the US PSORIQoL: a psoriasis-specific measure of quality of life.
AB  - BACKGROUND: Several instruments are available for assessing impairment and
      disability associated with psoriasis. The first true psoriasis-specific quality
      of life (QoL) questionnaire suitable for use in clinical trials, the Psoriasis
      Index of Quality of Life (PSORIQoL), has recently been developed in the UK. The
      aim of the current study was to produce and validate a conceptually equivalent US
      version of the PSORIQoL with equally good psychometric properties. METHODS: A lay
      translation panel was employed to ensure that the wording of the questionnaire
      was appropriate for a US population. Semi-structured interviews conducted with 37
      patients tested the instrument's ease of completion, relevance and
      comprehensiveness. Finally, a test-retest validation mail survey was conducted
      with 72 patients to determine reliability, internal consistency and construct
      validity. RESULTS: Few changes were necessary to the wording of the
      questionnaire. Interviewees found the questionnaire easy to complete (requiring
      an average of 4 min) and the content relevant and comprehensive. The adapted
      measure had comparable psychometric properties to the original, with a test
      retest reliability coefficient of 0.90, indicating excellent reproducibility.
      Internal consistency and initial indications of construct validity were also
      good, with scores on the measure related as expected to perceived general health
      and severity of psoriasis and the presence of visible lesions. CONCLUSIONS: The
      US PSORIQoL is a practical, reliable and valid instrument for measuring the
      impact of psoriasis and its treatment on QoL in clinical trials and in routine
      practice. It remains necessary to establish the instrument's responsiveness to
      changes in QoL associated with effective interventions.

PMID- 15941433
TI  - Pemphigus: analysis of 1209 cases.
AB  - BACKGROUND: Pemphigus is a rare and chronic life-threatening disease. The
      clinical picture varies in reports from different regions of the world.
      OBJECTIVE: To define the clinical forms of pemphigus in a large cohort of
      patients. METHODS: Prospective analysis of 1209 patients diagnosed and followed
      at the Pemphigus Research Unit, Tehran University for Medical Sciences, from 1984
      to 2003. RESULTS: The mean age at onset was 42 years with a female to male ratio
      of 1.5/1. The most frequent form was pemphigus vulgaris. In pemphigus vulgaris,
      patients' mucous membrane involvement alone was observed in 18%, skin involvement
      alone in 12%, and both in 70%. Pemphigus foliaceus was observed in 7% of the
      patients. Most complications were iatrogenic. CONCLUSION: In Iran, pemphigus
      vulgaris is the most frequent form of pemphigus. Females are more prone to the
      disease. The incidence of pemphigus in Tehran is approximately 1.6 per
      100,000/year, and in Iran 1.0 per 100,000/year. The age of onset was lower than
      classically reported. Death occurred in 6.2% of the patients. In pemphigus
      vulgaris, the mucosal and skin form together had a worse prognosis than the other
      clinical forms.

PMID- 15941434
TI  - Investigation of herpes simplex virus DNA in pityriasis rosea by polymerase chain
      reaction.
AB  - BACKGROUND: Pityriasis rosea (PR) is an acute, inflammatory disease of unknown
      cause. Clinical and experimental findings indicate an infectious etiology of PR.
      Our purpose is to examine the skin lesions and blood samples of PR patients by
      polymerase chain reaction (PCR) for the presence of HSV type 1 and 2 DNA.
      METHODS: The lesional skin biopsies from 10 patients and blood samples from two
      randomized patients with clinically and histologically confirmed pityriasis rosea
      were examined by PCR. RESULTS: No HSV 1 and HSV 2 DNA was detected in the
      lesional biopsy and blood samples. CONCLUSIONS: We could not identify a
      relationship between HSV 1, HSV 2 and PR.

PMID- 15941435
TI  - Digital imaging: a diagnostic screening tool?
AB  - BACKGROUND: Much interest has been shown in the possibility of using digital
      images to aid in the more rapid diagnosis of patients with dermatologic disease.
      A study was undertaken to test the efficacy of the "teledermatology" screening of
      referrals, and thereby to triage the patients to appropriate care. METHODS: A
      retrospective comparison of digital and "face-to-face" diagnoses by two
      consultant dermatologists was made. Eighty-four images from 75 patients seen in
      general dermatology clinics were studied. The clinical diagnosis and treatment
      plan of the patients seen in the clinic by one dermatologist were then compared
      with those suggested on digital image only, as seen by the other dermatologist.
      RESULTS: The diagnostic correlation between the two observers was fair, with full
      agreement in 47 of 84 cases (56%) and partial agreement in a further 10 (12%).
      There was no agreement in 14 cases (16.7%); in a further 13 cases, the images and
      history were not sufficient to allow a diagnosis to be made. The image quality
      was considered to be poor in 18 cases, but in six of these a diagnosis was still
      attempted. It was recommended that 66 patients (88%) should be seen in the
      hospital setting. Thirty patients (40%) received treatment at their visit.
      CONCLUSIONS: Teledermatology is not likely to have a great impact on reducing
      waiting lists. It is possible that it may help to prioritize referrals from
      remote areas.

PMID- 15941436
TI  - Survey of bacteriological contamination of cosmetic creams in Iran (2000).
AB  - The bacteriological quality of a variety of unused and used cosmetic creams was
      investigated. A 1-g sample from each product was aseptically placed in 9 ml of
      sterile Tween-peptone diluent, and 10-fold serial dilutions were prepared. The
      pour plate technique was used for aerobic bacterial colony counts, and
      microorganisms that grew in the culture were identified. The incidence of
      contamination by Gram-positive Bacilli, Staphylococcus aureus and non Escherichia
      coli Gram-negative organisms was found to be higher for used cosmetic creams
      (54%, 38% and 8%, respectively) than for unused creams (38%, 25% and 0%,
      respectively). Viable microorganisms were not recovered from 17% of the unused
      items whilst only 10% of the used creams did not contain viable microorganisms.
      The significance of the results is discussed and the importance of adopting
      suitable quality control guidelines is highlighted.

PMID- 15941437
TI  - Pigmented purpuric dermatosis and hepatitis profile: a report on 10 patients.
AB  - BACKGROUND: Pigmented purpuric dermatosis comprises a group of vascular disorders
      of unknown etiology. Histologically, it is characterized by lymphocytic
      capillaritis in the papillary dermis. Although leukocytoclastic vasculitis
      confined to the skin is frequently reported with hepatitis C, lymphocytic
      vasculitis is rarely reported. METHODS: Ten patients with pigmented purpuric
      dermatosis were studied clinically and histopathologically. Hepatitis profile was
      carried out in all of the patients to evaluate the possible relation. RESULTS: Of
      the 10 patients, five tested positive for hepatitis C and two for hepatitis B
      antibodies. CONCLUSION: Hepatitis C and B virus may play a role in the
      pathogenesis of pigmented purpuric dermatosis. Further case-control studies are
      necessary to confirm this conclusion.

PMID- 15941438
TI  - Lichen scrofulosorum: a prospective study of 39 patients.
AB  - BACKGROUND: Lichen scrofulosorum is considered a rare form of cutaneous
      tuberculosis. Current information is based on case reports and case series with a
      small number of patients. METHODS: Thirty-nine patients with Lichen scrofulosorum
      were followed during the period January 1996 to December 2002. Clinical details
      (age, sex, duration of disease, associated tubercular lesions, extent and
      distribution of skin lesions), laboratory parameters (hemoglobin, total
      leucocytic counts, erythrocyte sedimentation rate, Mantoux test, presence of BCG
      scar), and response to antitubercular treatment were recorded and analyzed.
      RESULTS: 7.6% patients of all (511) patients with cutaneous tuberculosis had LS.
      22 (56.4%) were males and 32 (84%) were below 15 years of age. Twenty-eight (72%)
      had an associated focus of tuberculosis elsewhere in the body; 13 (33%) had
      tubercular lymphadenopathy, while 11 (28%), three (8%) and six (15%) had
      pulmonary tuberculosis, intracranial tuberculosis and other forms of cutaneous
      tuberculosis, respectively. Six (15%) had tubercular focus at multiple sites.
      Eleven (28%) had no other identifiable focus of tuberculosis. Twenty-eight (72%)
      had evidence of receiving BCG vaccination. Trunk was the commonest (100%)
      affected site. The two groups with and without associated tubercular focus were
      not different with respect to age, sex, duration of disease, hemoglobin, total
      leukocyte count, erythrocyte sedimentation rate, Mantoux test positivity, and
      presence of BCG scar. Mycobacteria tuberculosis could not be detected either on
      acid fast bacilli (AFB) staining or on culture from biopsies of LS lesions. All
      patients (including those without evidence of tubercular focus) responded to
      antitubercular treatment, signifying an underlying occult tubercular focus as
      etiology. CONCLUSIONS: Lichen scrofulosorum is an uncommon but not rare cutaneous
      manifestation of tuberculosis. A high index of suspicion and awareness is
      required for diagnosis. Systemic tuberculosis is often associated with LS and a
      prior BCG inoculation does not protect against development of LS. Response to
      antitubercular treatment is good irrespective of the presence or absence of
      associated tubercular focus.

PMID- 15941439
TI  - Post-kala-azar dermal leishmaniasis with visceral leishmaniasis: a rare
      presentation.

PMID- 15941440
TI  - Erysipeloid.

PMID- 15941441
TI  - Nevus comedonicus syndrome: a case associated with multiple basal cell carcinomas
      and a rudimentary toe.

PMID- 15941442
TI  - Improvement in lymphatic function and partial resolution of nails after complex
      decongestive physiotherapy in yellow nail syndrome.

PMID- 15941443
TI  - Anetoderma developing in juvenile xanthogranuloma.

PMID- 15941444
TI  - Microcystic adnexal carcinoma: report of four cases treated with Mohs'
      micrographic surgical technique.
AB  - BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare and aggressive
      malignant tumor of the sweat glands. Clinically, it often presents as a firm
      subcutaneous nodule on the head and neck regions. On histology, MAC exhibits both
      pilar and sweat duct differentiation with a stroma of dense collagen. It often
      extends beyond the clinical margins with local spreading in the dermal,
      subcutaneous, and perineural tissue planes. It has a high local recurrence rate
      after standard excision. Recent preliminary reports have indicated more favorable
      cure rates with Mohs' micrographic surgery (MMS). OBJECTIVE: To present our data
      on four cases of MAC treated by MMS. We also compared our findings with more
      recently reported series in the English language literature. METHODS: We reviewed
      the medical records of four patients (two males and two females) with MAC treated
      by MMS over the last 3 years. We also obtained follow-up data. RESULTS: In all
      four patients with MAC treated by MMS, there were no recurrences, with a mean
      follow-up of 1 year. CONCLUSION: We report an additional four MAC cases treated
      by MMS. The accumulated data continue to confirm that, if the diagnosis of MAC is
      made early, and if the anatomic location is accessible to excision by MMS, a
      favorable outcome can be expected.

PMID- 15941445
TI  - Radiotherapy of skin carcinomas of the pinna: a study of 115 lesions in 108
      patients.
AB  - BACKGROUND: The possibility of treating skin carcinomas of the pinna with
      radiotherapy is somewhat under discussion and scarcely known. Therefore the aim
      of the study was to evaluate the effectiveness and safety of dermatologic
      radiotherapy in a series of patients affected by basal or squamous cell carcinoma
      of the pinna. METHODS: A retrospective study was performed on 108 patients
      affected by 115 carcinomas of the pinna (99 basal cell carcinomas, 16 squamous
      cell carcinomas) without involvement of the external auditory canal. Radiotherapy
      was performed with kilovoltage techniques (55-120 kV) and the total doses
      administered ranged from 45 to 70 Gy (105 Gy in one case only), with different
      fractionations. RESULTS: The mean follow-up was 28.80 months. Complete remission
      was obtained in 111 lesions (96.52%) and partial remission in one (0.87%), as
      evaluated 1 month after the end of radiotherapy. No response was observed in two
      lesions (1.74%). The response was not evaluable in one lesion (0.87%). During
      follow up a relapse was observed in 12 lesions (all basal cell carcinomas): nine
      central and three marginal to the irradiation field. The 5-year cure-rate from
      the end of radiotherapy was 78%. The cosmetic results were evaluated as good or
      acceptable in 88.28% of lesions. No complications nor sequelae to the treatment
      were observed. CONCLUSIONS: The results obtained confirm the possibility of
      treating epithelial skin neoplasms of the pinna with dermatologic radiotherapy,
      which can afford high-remission percentages without damaging cartilaginous
      tissue.

PMID- 15941446
TI  - Mycobacterium marinum with different responses to second-generation
      tetracyclines.
AB  - BACKGROUND: Persistent cutaneous infections with Mycobacterium marinum can follow
      exposure of injured skin to contaminated water or fish, and can be treated with
      second-generation tetracyclines in addition to other antimicrobials. Due to the
      rarity of this infection, there are few data comparing the different treatment
      alternatives. METHODS: We report a patient with culture-proven M. marinum who was
      treated with two different second-generation tetracyclines. RESULTS: Our patient
      failed a 4-week trial of doxycycline, but responded rapidly to minocycline.
      CONCLUSION: This case suggests that, despite a similar mechanism,
      pharmacokinetics, and even sensitivity, these two agents may differ in their
      effectiveness against strains of M. marinum.

PMID- 15941447
TI  - Lichen scrofulosorum: current status.

PMID- 15941448
TI  - Morphea with features of lichen sclerosus et atrophicus at the site of a herpes
      zoster scar: another case of an isotopic response.

PMID- 15941449
TI  - [Comment on "Wolf's isotopic response: herpes simplex appearing on scrofuloderma
      scar."].

PMID- 15941451
TI  - Omega-3, omega-6 and psoriasis: a different view.

PMID- 15941453
TI  - Exacerbation of palmoplantar pustulosis by granulocyte colony-stimulating factor.

PMID- 15941455
TI  - Day treatment programme for patients with eating disorders: randomized controlled
      trial.
AB  - AIM: This paper reports a randomized controlled trial to compare the effects of
      day treatment programmes for patients with eating disorders with those of
      traditional outpatient treatment. BACKGROUND: Eating disorders are common,
      especially in adolescents, and their worldwide prevalence is increasing.
      Treatment interventions for patients with eating disorders have traditionally
      been offered on an outpatient or inpatient basis, but the recent introduction of
      day hospital programmes offers the possibility of greater cost-effectiveness and
      relapse-prevention for this population. METHODS: Volunteers from an outpatient
      clinic for eating disorders were randomly assigned either to a treatment group (n
      = 21), participating in a modified day treatment programme based on the Toronto
      Day Hospital Program, or to a control group (n = 22) receiving a traditional
      outpatient programme of interpersonal psychotherapy, cognitive behaviour therapy
      and pharmacotherapy. Data were collected from January to December 2002 using the
      Eating Disorder Examination, Eating Disorder Inventory-2, Beck Depression
      Inventory, and Rosenberg Self-Esteem Scale. RESULTS: Participants in the day
      treatment programme showed significantly greater improvements on most
      psychological symptoms of the Eating Disorder Inventory-2, frequency of binging
      and purging, body mass index, depression and self-esteem scores than the control
      group. They also showed significant improvement in perfectionism, but the group
      difference was not significant. CONCLUSION: Nurses in day treatment programmes
      can play various and important roles establishing a therapeutic alliance between
      patient and carer in the initial period of treatment. In addition, the cognitive
      and behavioural work that is vital to a patient's recovery, that is, dealing with
      food issues, weight issues and self-esteem, is most effectively provided by a
      nurse therapist who maintains an empathic involvement with the patient.

PMID- 15941456
TI  - Quality of life of patients having renal replacement therapy.
AB  - AIM: This paper reports a study to compare the quality of life and its correlates
      for patients undergoing various types of renal replacement therapy. BACKGROUND:
      Patients with end stage renal disease need renal replacement therapy as a
      substitute for their original kidneys. Different renal replacement therapies have
      different levels of impact on physical, psychological and social health. Quality
      of life as perceived by patients with end-stage renal disease is an important
      measure of patient outcome. METHODS: A cross-sectional, descriptive,
      correlational study was carried out in 2002. A total of 240 patients were
      recruited from two medical centres in northern Taiwan. These patients were
      currently undergoing one of following types of renal replacement therapies:
      haemodialysis, continuous ambulatory peritoneal dialysis or transplantation. The
      study instrument used was the WHOQOL-BREF-TAIWAN. Data were analysed using
      descriptive and inferential statistics. RESULTS: The scores for quality of life
      of transplantation patients were higher than those for both haemodialysis and
      continuous ambulatory peritoneal dialysis patients. The lowest scores for all
      three groups were in the psychological domain. The mean age for haemodialysis and
      continuous ambulatory peritoneal dialysis patients was significantly higher than
      that for transplant patients. The educational level, proportion of single people,
      and employment status of transplant patients were significantly higher than those
      of haemodialysis and continuous ambulatory peritoneal dialysis patients.
      Perception of economic status as 'balanced' or 'proficient' for transplant
      patients was significantly higher than for continuous ambulatory peritoneal
      dialysis and haemodialysis patients. CONCLUSION: Information about the quality of
      life of patients having various types of renal replacement therapy will assist
      physicians, nurses, patients and their families to make decisions on treatment
      selection. There is a need to establish support groups for patients having renal
      replacement therapy in order to enhance their quality of life, especially in the
      psychological domain.

PMID- 15941457
TI  - HIV/AIDS and the workplace: perceptions of nurses in a public hospital in South
      Africa.
AB  - AIM: The purpose of this article is to report a study of the perceptions and
      experiences of nurses caring for people living with HIV/AIDS in the public health
      sector in South Africa. BACKGROUND: The number of people living with HIV/AIDS in
      South Africa has escalated at an alarming rate. Many people being hospitalized
      are HIV positive, and hence nurses are in more regular and prolonged contact with
      people suffering from HIV/AIDS than is the case in other working environments.
      Although studies focusing on nurses' experiences of caring for patients with
      HIV/AIDS have been done in numerous countries, little is known about nurses'
      views in Africa, and South Africa in particular. To ensure quality care for
      patients with HIV/AIDS, it is important to understand nurses' experiences of
      nursing HIV-positive patients and how they may influence their attitudes towards
      these patients. METHOD: A qualitative approach was used, the primary method of
      data collection being in-depth interviews. These interviews were conducted with
      35 nurses at a public hospital in the Gauteng province of South Africa in 2002
      2003. FINDINGS: Seven themes were identified: helplessness, emotional stress and
      fatigue, fear, anger and frustration, occupational-related concerns, empathy, and
      self-fulfilment. CONCLUSIONS: Increased understanding of the stresses and rewards
      experienced by these nurses can contribute to policy development in this area. It
      is also important to provide appropriate preregistration and continuing education
      and support for nurses working in this field, and to ensure that the working
      environment is adequate in terms of resources.

PMID- 15941458
TI  - Depressive symptoms in long-term care residents in Taiwan.
AB  - AIM: This paper reports a study to investigate the prevalence of and risk factors
      for depressive symptoms in elders in long-term care facilities in Taiwan.
      BACKGROUND: Depression has been identified as a major health concern and is very
      common among frail elders in Western nursing homes. It is under-diagnosed, and
      may be associated with eating difficulties and subsequent malnutrition,
      functional ability and sociodemographic factors. There have been no previous
      studies of these issues in Taiwan. METHODS: Residents of 18 long-term care
      facilities were recruited. Those able to communicate in the Mandarin or Taiwanese
      dialect, resided in long-term care facilities including skilled nursing
      facilities and intermediate care facilities, and who scored three or above on the
      Short Portable Mental Status Questionnaire were selected. Data were collected
      using the Geriatric Depression Scale, Barthel Index and Masticatory Index, and
      age, duration of institutionalization, and level of impaired swallowing were also
      measured. RESULTS: The number of participants identified as depressed was 267
      (52.05%). There was no significant difference noted relating to age, gender,
      duration of institutionalization, type of institution, mental status and
      masticatory ability between the depressed and non-depressed groups, but
      significant differences of functional status and impaired swallowing between the
      two groups were found. However, functional status, impaired swallowing, and type
      of institution were three independent factors associated with depressive symptoms
      after controlling for all other factors. CONCLUSIONS: Future studies on the
      detection of symptoms of depression should use a validated observational measure
      to overcome under-reporting of symptoms by the frailest residents.

PMID- 15941459
TI  - Nurses' and midwives' assertive behaviour in the workplace.
AB  - AIM: This paper reports a study describing the assertive behaviour of a group of
      professional nurses and midwives and exploring potential barriers and
      facilitators to the use of assertiveness skills in the workplace. BACKGROUND: As
      nurses and midwives move away from traditional roles, it is increasingly being
      recognized that they need to behave in an assertive manner. Much literature
      supports the use of assertive behaviour in clinical practice. Although specific
      individual assertive behaviours and skills have been examined in many settings,
      little empirical evidence exists about the frequency and use of assertiveness
      skills by nurses and midwives in the workplace. While there is evidence on
      barriers to the use of assertive skills, there is little information about
      factors that may facilitate their use. METHOD: A survey design was adopted, using
      a 44-item questionnaire to collect data from a 2.5% random sample of
      nurses/midwives registered with the National Nursing Board of Ireland. The data
      were collected in 2003. RESULTS: While respondents frequently complimented their
      colleagues and often allowed them to express opinions, they were less
      accomplished at expressing their own opinions or making requests. Assertive
      behaviours were used more frequently with nursing/midwifery colleagues than with
      management/medical colleagues. Most used assertiveness skills with other grades
      of staff in their own profession. Responsibility to patients/clients emerged as a
      supporting factor for using assertive behaviour. Managers, the work atmosphere
      and fear were viewed as obstacles. CONCLUSION: Nurses and midwives needs to learn
      how to behave assertively, and this should be included in both pre- and post
      registration education programmes. As use of assertiveness skills was reported to
      be least frequent with nurse/midwife managers, local policies and guidelines may
      be needed to encourage clinical practitioners to act autonomously and as client
      advocates.

PMID- 15941460
TI  - The social construction of 'reproductive vulnerability' in family planning
      clinics.
AB  - AIM: The aim of this paper is to report a study exploring the discursive
      construction of contraceptive use within nurse consultations with women in family
      planning clinics. BACKGROUND: This paper takes as its starting point the lack of
      a contraceptive 'strand' to the literature on the discursive construction of the
      female body generally, and the female reproductive system specifically, within
      health care practice. The literature in this field concentrates on pregnancy,
      menstruation and menopause, and the manner in which contraceptive use is
      discursively constructed is under-explored. Furthermore, the literature on nurse
      women consultations in family planning clinics is also limited, with the current
      literature concentrating on assessing clinical skills rather than discourse.
      METHODS: Using a grounded theory methodology to explore how nurses educate women
      about contraception in family planning clinic, 49 consultations were audio-taped
      in two large family planning clinics in the United Kingdom (UK). FINDINGS: Open
      coding and subsequent axial coding resulted in the emergence of three elements of
      contraceptive education. One concerned reproductive anatomy, another reproductive
      physiology and a third education about contraceptive functioning. These three
      axial codes were formed into a core category: 'body education/reproductive
      vulnerability'. Within the consultation, nurses linked the 'vulnerable'
      reproductive system with the requirement for contraceptive 'protection'. This
      approach seems linked to ensuring women's future contraceptive use. CONCLUSION:
      The discourse employed by nurses differs from the body discourse aimed at
      menopause and menstruation. These areas of women's health were constructed as
      disintegrating, malfunctioning and failing, whereas reproductive vulnerability
      suggests a fully functioning, active system, in need of restraint. However, this
      discourse still constructs the female body as fundamentally weak and unstable,
      requiring contraception to protect it and prevent transgression.

PMID- 15941461
TI  - Discourse analysis: towards an understanding of its place in nursing.
AB  - AIM: This paper describes how discourse analysis, and in particular critical
      discourse analysis, can be used in nursing research, and provides an example to
      illustrate the techniques involved. BACKGROUND: Discourse analysis has risen to
      prominence in the 1980s and 1990s in disciplines such as the social sciences,
      literary theory and cultural studies and is increasingly used in nursing. This
      paper investigates discourse analysis as a useful methodology for conducting
      nursing research. Effective clinical reasoning relies on employing several
      different kinds of knowledge and research that draw on different perspectives,
      methodologies and techniques to generate breadth of knowledge and depth of
      understanding of clinical practices and patients' experiences of those practices.
      DISCUSSION: The steps in a discourse analysis include: choosing the text, and
      identifying the explicit purpose of the text, the processes used for claiming
      authority connections to other discourses, construction of major concepts,
      processes of naming and categorizing, construction of subject positions,
      construction of reality and social relations and implications for the practice of
      nursing. The limitations of discourse analysis, its relationship to other
      qualitative approaches and questions for evaluating the rigour of research using
      discourse analysis are also explored. The example of discourse analysis shows how
      a text influences the practice of nursing by shaping knowledge, values and
      beliefs. CONCLUSION: Discourse analysis can make a contribution to the
      development of nursing knowledge by providing a research strategy to examine
      dominant discourses that influence nursing practice.

PMID- 15941462
TI  - Producing the magnum opus: a metaphor for nephrology nursing expertise
      acquisition.
AB  - AIM: This paper elucidates the nature of metaphor and the conditions necessary to
      its use as an analytic device in qualitative research, and describes how the use
      of metaphor assisted in the analytic processes of a grounded theory study of
      nephrology nursing expertise. BACKGROUND: The use of metaphor is pervasive in
      everyday thought, language and action. It is an important means for the
      comprehension and management of everyday life, and makes challenging or
      problematic concepts easier to explain. Metaphors are also pervasive in
      quantitative and qualitative research for the same reason. In both everyday life
      and in research, their use may be implicit or explicit. METHODS: The study using
      grounded theory methodology took place in one renal unit in New South Wales,
      Australia between 1999 and 2000 and included six non-expert and 11 expert nurses.
      It involved simultaneous data collection and analysis using participant
      observation, semi-structured interviews and review of nursing documentation.
      FINDINGS: A three stage skills-acquisitive process was identified in which an
      orchestral metaphor was used to explain the relationships between stages and to
      satisfactorily capture the data coded within each stage. CONCLUSION: Metaphors
      create images, clarify and add depth to meanings and, if used appropriately and
      explicitly in qualitative research, can capture data at highly conceptual levels.
      Metaphors also assist in explaining the relationship between findings in a clear
      and coherent manner.

PMID- 15941463
TI  - Relationship between quality of care, staffing levels, skill mix and nurse
      autonomy: literature review.
AB  - AIMS: This paper reports a literature review exploring the relationship between
      quality of care and selected organizational variables through a consideration of
      what is meant by perceptions of quality, whose perceptions are accorded
      prominence, and whether changes in staffing, skill mix and autonomy affect
      perceptions of quality. BACKGROUND: Three basic ideas underpin this literature
      review: the growing focus on quality improvement in health care, concerns about
      the quality of care, and the move towards patient involvement and consultation.
      Of particular interest is the way in which changes in nurse staffing, skill mix
      and autonomy may affect the delivery of quality patient care. METHODS: A search
      was conducted using the CINAHL, Medline and Embase databases. Key words used were
      quality of health care; quality of nursing care; nurse; patient; skill mix; nurse
      patient ratio; outcomes; adverse health care events and autonomy. The objective
      was to draw together a diverse collection of literature related to the field of
      health care quality. Papers were included for their relevance to the field of
      enquiry. The original search was conducted in 2003 and updated in 2004. FINDINGS:
      Quality of care is a complex, multi-dimensional concept which presents
      researchers with a challenge when attempting to evaluate it. Traditional nursing
      assessment tools have fallen out of use, partly because they have failed to
      provide opportunities to engage with and access the views of patients or nurses.
      There is also evidence that patient satisfaction as an indicator of quality is
      compromised on a number of fronts. There is conflicting information on how nurses
      and patients think about quality. Research looking at the relationship between
      the selected organizational variables and perceptions of quality also suffers
      from a number of limitations. We argue that there is a requirement for more
      patient-centred research exploring perceptions of quality and differences in
      nurse staffing, skill mix and autonomy.

PMID- 15941465
TI  - A response to L. Kemp, E. Harris & E. Comino Changes in community nursing in
      Australia: 1995-2000.

PMID- 15941464
TI  - Graduated compression stockings as prophylaxis for flight-related venous
      thrombosis: systematic literature review.
AB  - AIM: This paper reports a systematic review whose objective was to evaluate the
      effectiveness of graduated compression stockings as prophylaxis for flight
      related venous thrombosis, including deep vein thrombosis and superficial venous
      thrombosis, after air travel in the general population. BACKGROUND: Despite the
      extended history of the use of graduated compression stockings, their application
      to prevent flight-related thrombosis was not explored until flight-related
      thrombosis was perceived as a preventable illness. Even now, their effectiveness
      in preventing flight-related thrombosis remains unresolved. METHODS: Generic
      terms including stocking/s, sock/s, or hosiery/hosieries were used to search a
      variety of electronic databases. Based on the selection criteria, decisions
      regarding inclusion and exclusion of primary studies were made. Using a meta
      analysis software program, relative risk for the incidence of deep vein
      thrombosis, superficial venous thrombosis, and intention-to-treat analysis was
      calculated. RESULTS: A total of nine randomized controlled trials were included.
      In the treatment group, two of 1237 participants developed deep vein thrombosis
      in comparison with 46 of 1245 in the control group. The weighted relative risk
      for deep vein thrombosis was 0.08, with fixed 95% confidence interval 0.03-0.23.
      In the treatment group, four of 826 participants developed superficial venous
      thrombosis in comparison with seven of 823 in the control group. The weighted
      relative risk for superficial venous thrombosis was 0.67. with fixed 95%
      confidence interval 0.24-1.87 (non-significant difference). Using intention-to
      treat analysis, the risk for participants in the treatment group was 0.53 times
      as great as that for those in the control group. CONCLUSIONS: This review
      demonstrates the effectiveness of medium compression pressure, below-knee
      graduated compression stockings in preventing flight-related deep vein thrombosis
      but not superficial venous thrombosis in low-medium- or high-risk participants.

PMID- 15941469
TI  - BMC Bioinformatics comes of age.

PMID- 15941470
TI  - Nuclear distribution and chromatin association of DNA polymerase alpha-primase is
      affected by TEV protease cleavage of Cdc23 (Mcm10) in fission yeast.
AB  - BACKGROUND: Cdc23/Mcm10 is required for the initiation and elongation steps of
      DNA replication but its biochemical function is unclear. Here, we probe its
      function using a novel approach in fission yeast, involving Cdc23 cleavage by the
      TEV protease. RESULTS: Insertion of a TEV protease cleavage site into Cdc23
      allows in vivo removal of the C-terminal 170 aa of the protein by TEV protease
      induction, resulting in an S phase arrest. This C-terminal fragment of Cdc23 is
      not retained in the nucleus after cleavage, showing that it lacks a nuclear
      localization signal and ability to bind to chromatin. Using an in situ chromatin
      binding procedure we have determined how the S phase chromatin association of DNA
      polymerase alpha-primase and the GINS (Sld5-Psf1-Psf2-Psf3) complex is affected
      by Cdc23 inactivation. The chromatin binding and sub-nuclear distribution of DNA
      primase catalytic subunit (Spp1) is affected by Cdc23 cleavage and also by
      inactivation of Cdc23 using a degron allele, implying that DNA polymerase alpha
      primase function is dependent on Cdc23. In contrast to the effect on Spp1, the
      chromatin association of the Psf2 subunit of the GINS complex is not affected by
      Cdc23 inactivation. CONCLUSION: An important function of Cdc23 in the elongation
      step of DNA replication may be to assist in the docking of DNA polymerase alpha
      primase to chromatin.

PMID- 15941471
TI  - Statins research unfinished saga: desirability versus feasibility.
AB  - Drugs in the same class are generally thought to be therapeutically equivalent
      because of similar mechanisms of action (the so-called "class effect"). However,
      statins differ in multiple characteristics, including liver and renal metabolism,
      half-life, effects on several serum lipid components, bioavailability and
      potency. Some are fungal derivatives, and others are synthetic compounds. The
      percentage absorption of an oral dose, amount of protein binding, degree of renal
      excretion, hydrophilicity, and potency on a weight basis is variable. These
      differences may be even greater in diabetic patients, who may present diabetes
      induced abnormalities in P450 isoforms and altered hepatic metabolic pathways.
      Thus, it is obvious that head-to-head comparisons between different statins are
      preferable than trial-to-trial comparisons. Such assessments are of utmost
      importance, especially in cases in which specific populations with a distinct
      lipid profile and altered metabolic pathways, like diabetics, are studied. It
      should be specially pinpointed that patients with metabolic syndrome and diabetes
      constitute also a special population regarding their atherogenic dyslipidemia,
      which is usually associated with low HDL-cholesterol, hypertriglyceridemia and
      predominance of small dense LDL-cholesterol. Therefore, these patients may
      benefit from fibrates or combined statin/fibrate treatment. This policy is not
      accomplished since in the real world things are more complex. Trials would
      require very large sample sizes and long-term follow-up to detect significant
      differences in myocardial infarction or death between two different statins.
      Moreover, the fact that new compounds are under several phases of research and
      development represents an additional drawback for performing the trials. Ideally,
      head-to-head trials regarding clinically important outcomes should be conducted
      for all drugs. Nonetheless, the desirability of performing such trials, which
      epitomize modern evidence-based medicine, is frequently superseded by the
      feasibility dictated by pragmatic and economic circumstances. In the latter case,
      in absence of solid systematic documentation of comparable health benefits and
      long-term safety, both researchers and practicing physicians should allude to the
      weight of scientific endorsement behind the arguments and seek for the possible
      strengths and weaknesses intrinsic to each specific study. In any case,
      conclusions based on surrogate endpoints cannot completely substitute head-to
      head comparisons regarding patients' outcome.

PMID- 15941472
TI  - Effect of electro-acupuncture on ovarian expression of alpha (1)- and beta (2)
      adrenoceptors, and p75 neurotrophin receptors in rats with steroid-induced
      polycystic ovaries.
AB  - BACKGROUND: Estradiol valerate (EV)-induced polycystic ovaries (PCO) in rats is
      associated with an increase in ovarian sympathetic outflow. Low-frequency (2 Hz)
      electro-acupuncture (EA) has been shown to modulate sympathetic markers as well
      as ovarian blood flow as a reflex response via the ovarian sympathetic nerves, in
      rats with EV-induced PCO. METHODS: In the present study, we further tested the
      hypothesis that repeated 2 Hz EA treatments modulate ovarian sympathetic outflow
      in rats with PCO, induced by a single i.m. injection of EV, by investigating the
      mRNA expression, the amount and distribution of proteins of alpha1a-, alpha1b-,
      alpha1d-, and beta2-adrenoceptors (ARs), as well as the low-affinity neurotrophin
      receptor (p75NTR). RESULTS: It was found that EV injection results in
      significantly higher mRNA expression of ovarian alpha1b- and alpha1d-AR in PCO
      rats compared to control rats. The p75NTR and beta2-ARs mRNA expression were
      unchanged in the PCO ovary. Low-frequency EA resulted in a significantly lower
      expression of beta2-ARs mRNA expression in PCO rats. The p75NTR mRNA was
      unaffected in both PCO and control rats. PCO ovaries displayed significantly
      higher amount of protein of alpha1a-, alpha1b- and alpha1d-ARs, and of p75NTR,
      compared to control rats, that were all counteracted by repeated low-frequency EA
      treatments, except for alpha1b-AR. CONCLUSION: The present study shows that EA
      normalizes most of the EV-induced changes in ovarian ARs. Furthermore, EA was
      able to prevent the EV-induced up regulation of p75NTR, probably by normalizing
      the sympathetic ovarian response to NGF action. Our data indicate a possible role
      of EA in the regulation of ovarian responsiveness to sympathetic inputs and
      depict a possible complementary therapeutic approach to overcoming sympathetic
      related anovulation in women with PCOS.

PMID- 15941473
TI  - Discovery of protein-protein interactions using a combination of linguistic,
      statistical and graphical information.
AB  - BACKGROUND: The rapid publication of important research in the biomedical
      literature makes it increasingly difficult for researchers to keep current with
      significant work in their area of interest. RESULTS: This paper reports a
      scalable method for the discovery of protein-protein interactions in Medline
      abstracts, using a combination of text analytics, statistical and graphical
      analysis, and a set of easily implemented rules. Applying these techniques to
      12,300 abstracts, a precision of 0.61 and a recall of 0.97 were obtained, (f =
      0.74) and when allowing for two-hop and three-hop relations discovered by
      graphical analysis, the precision was 0.74 (f = 0.83). CONCLUSION: This
      combination of linguistic and statistical approaches appears to provide the
      highest precision and recall thus far reported in detecting protein-protein
      relations using text analytic approaches.

PMID- 15941474
TI  - Willingness to pay to assess patient preferences for therapy in a Canadian
      setting.
AB  - BACKGROUND: Adult outpatient parenteral antibiotic therapy (OPAT) programs have
      been reported in the literature for over 20 years, however there are no published
      reports quantifying preference for treatment location of patients referred to an
      OPAT program. The purpose of this study was to elicit treatment location
      preferences and willingness to pay (WTP) from patients referred to an OPAT
      program. METHODS: A multidisciplinary, single centre, prospective study at a 1000
      bed Canadian adult tertiary care teaching hospital. This study involved a WTP
      questionnaire that was administered over a 9-month study period. Eligible and
      consenting patients referred to the OPAT program were asked to state their
      preference for treatment location and WTP for a hypothetical treatment scenario
      involving intravenous antibiotic therapy. Multiple linear regression analysis was
      performed to determine predictors of WTP. RESULTS: Of 131 eligible patients, 91
      completed the WTP questionnaire. The majority of participants were males,
      married, in their sixth decade of life and had a secondary school education or
      greater. The majority of participants were retired or they were employed with
      annual household incomes less than 60,000 dollars. Osteomyelitis was the most
      common type of infection for which parenteral therapy was required. Of those 87
      patients who indicated a preference, 77 (89%) patients preferred treatment at
      home, 10 (11%) patients preferred treatment in hospital. Seventy-one (82%) of
      these patients provided interpretable WTP responses. Of these 71 patients, 64
      preferred treatment at home with a median WTP of 490 dollars CDN (mean 949
      dollars, range 20 to 6250 dollars) and 7 preferred treatment in the hospital with
      a median WTP of 500 dollars CDN (mean 1123 dollars, range 10 to 3000 dollars).
      Tests for differences in means and medians revealed no differences between WTP
      values between the treatment locations. The total WTP for the seven patients who
      preferred hospital treatment was 7,859 dollars versus 60,712 dollars for the 64
      patients who preferred home treatment. Income and treatment location preference
      were independent predictors of WTP. CONCLUSION: This study reveals that treatment
      at home is preferred by adult inpatients receiving intravenous antibiotic therapy
      that are referred to our OPAT program. Income and treatment location appear to be
      independently associated with their willingness to pay.

PMID- 15941475
TI  - Enhanced detergent extraction for analysis of membrane proteomes by two
      dimensional gel electrophoresis.
AB  - BACKGROUND: The analysis of hydrophobic membrane proteins by two-dimensional gel
      electrophoresis has long been hampered by the concept of inherent difficulty due
      to solubility issues. We have optimized extraction protocols by varying the
      detergent composition of the solubilization buffer with a variety of commercially
      available non-ionic and zwitterionic detergents and detergent-like phospholipids.
      RESULTS: After initial analyses by one-dimensional SDS-PAGE, quantitative two
      dimensional analyses of human erythrocyte membranes, mouse liver membranes, and
      mouse brain membranes, extracted with buffers that included the zwitterionic
      detergent MEGA 10 (decanoyl-N-methylglucamide) and the zwitterionic lipid LPC (1
      lauroyl lysophosphatidylcholine), showed selective improvement over extraction
      with the common 2-DE detergent CHAPS (3 [(3-cholamidopropyl)dimethylammonio]-1
      propanesulfonate). Mixtures of the three detergents showed additive improvements
      in spot number, density, and resolution. Substantial improvements in the analysis
      of a brain membrane proteome were observed. CONCLUSION: This study demonstrates
      that an optimized detergent mix, coupled with rigorous sample handling and
      electrophoretic protocols, enables simple and effective analysis of membrane
      proteomes using two-dimensional electrophoresis.

PMID- 15941476
TI  - Chemistry in bioinformatics.
AB  - Chemical information is now seen as critical for most areas of life sciences. But
      unlike Bioinformatics, where data is openly available and freely re-usable, most
      chemical information is closed and cannot be re-distributed without permission.
      This has led to a failure to adopt modern informatics and software techniques and
      therefore paucity of chemistry in bioinformatics. New technology, however, offers
      the hope of making chemical data (compounds and properties) free during the
      authoring process. We argue that the technology is already available; we require
      a collective agreement to enhance publication protocols.

PMID- 15941477
TI  - Which gene did you mean?
AB  - Computational Biology needs computer-readable information records. Increasingly,
      meta-analysed and pre-digested information is being used in the follow up of high
      throughput experiments and other investigations that yield massive data sets.
      Semantic enrichment of plain text is crucial for computer aided analysis. In
      general people will think about semantic tagging as just another form of text
      mining, and that term has quite a negative connotation in the minds of some
      biologists who have been disappointed by classical approaches of text mining.
      Efforts so far have tried to develop tools and technologies that retrospectively
      extract the correct information from text, which is usually full of ambiguities.
      Although remarkable results have been obtained in experimental circumstances, the
      wide spread use of information mining tools is lagging behind earlier
      expectations. This commentary proposes to make semantic tagging an integral
      process to electronic publishing.

PMID- 15941478
TI  - Surgical management of abdominal and retroperitoneal Castleman's disease.
AB  - BACKGROUND: Abdominal and retroperitoneal Castleman's disease could present
      either as a localized disease or as a systemic disease. Castleman's disease is a
      lymphoid hyperplasia related to human Herpes virus type 8, which could have an
      aggressive behavior, similar to that of malignant lymphoid neoplasm mainly with
      the systemic type, or a benign one in its localized form. METHODS: The authors
      report two cases of localized Castleman's disease in the retroperitoneal space
      and review the current and recent progress in the knowledge of this atypical
      disease. CASES PRESENTATION: The two patients were young healthy women presenting
      with a hyper vascular peri-renal mass suggestive of malignant tumor. Both have
      been resected in-toto. One of them had an extensive resection with nephrectomy,
      while the second had a kidney preserving surgery. Pathological examination
      revealed localized Castleman's disease and surgical margins were free of disease.
      Postoperative course was uneventful, and after more than 5-years of follow-up no
      recurrences have been observed. CONCLUSION: Localized Castleman's disease should
      be considered when facing a solid hypervascular abdominal or retroperitoneal
      mass. A better knowledge of this disorder and its characteristic would help
      surgeon to avoid unnecessarily extensive resection for this benign disorder when
      dealing with abdominal or retroperitoneal tumors. Surgical resection is curative
      for the localized form, when complete, while splenectomy could be indicated for
      the systemic form.

PMID- 15941479
TI  - Transforming growth factor beta-1 decreases the yield of the second meiotic
      division of rat pachytene spermatocytes in vitro.
AB  - BACKGROUND: TGF beta and its receptors are present in both germ cells and somatic
      cells of the male gonad. However, knock-out strategies for studying
      spermatogenesis regulation by TGF beta have been disappointing since TGF beta-or
      TGF beta receptor-null mice do not survive longer than a few weeks. METHODS: In
      the present study, we addressed the role of TGF beta-1 on the completion of
      meiosis by rat pachytene spermatocytes (PS) cocultured with Sertoli cells.
      Identification and counting of meiotic cells were performed by cytology and
      cytometry. RESULTS: Under our culture conditions, some PS differentiated into
      round spermatids (RS). When TGF beta-1 was added to the culture medium, neither
      the number of PS or of secondary spermatocytes nor the half-life of RS was
      modified by the factor. By contrast, the number of RS and the amount of TP1 mRNA
      were lower in TGF beta-1-treated cultures than in control cultures. Very few
      metaphase I cells were ever observed both in control and TGF beta-1-treated
      wells. Higher numbers of metaphase II were present and their number was enhanced
      by TGF beta-1 treatment. A TGF beta-like bioactivity was detected in control
      culture media, the concentration of which increased with the time of culture.
      CONCLUSION: These results indicate that TGF beta-1 did not change greatly, if
      any, the yield of the first meiotic division but likely enhanced a bottleneck at
      the level of metaphase II. Taken together, our results suggest strongly that TGF
      beta participates in an auto/paracrine pathway of regulation of the meiotic
      differentiation of rat spermatocytes.

PMID- 15941480
TI  - Management of difficult airway in intratracheal tumor surgery.
AB  - BACKGROUND: Tracheal malignancies are usual victim of delay in diagnosis by
      virtue of their symptoms resembling asthma. Sometimes delayed diagnosis may lead
      to almost total airway obstruction. For difficult airways, not leaving any
      possibility of manipulation into neck region or endoscopic intervention,
      femorofemoral cardiopulmonary bypass can be a promising approach. CASE
      PRESENTATION: We are presenting a case of tracheal adenoid cystic carcinoma
      (cylindroma) occupying about 90% of the tracheal lumen. It was successfully
      managed by surgical excision of mass by sternotomy and tracheotomy under
      femorofemoral cardiopulmonary bypass (CPB). CONCLUSION: Any patient with
      recurrent respiratory symptoms should be evaluated by radiological and endoscopic
      means earlier to avoid delay in diagnosis of such conditions. Femorofemoral
      cardiopulmonary bypass is a relatively safe way of managing certain airway
      obstructions.

PMID- 15941482
TI  - Unexpected combination of acute croup and myocarditis: case report.
AB  - BACKGROUND: Lower vaccination coverage among foreign-born children is of concern
      because they live in households and communities characterized by more intense
      exposure to infectious diseases. Because of their higher prevalence rates, there
      is an increasing occurrence of infectious diseases imported into developed
      countries. This case report emphasizes the emerging necessity for new clinicians
      and pathologists of having competence with old infectious disease pathology. CASE
      PRESENTATION: A three and a half year old girl, who presented with croup history
      of 5 days and has been in severe respiratory distress, was admitted to the
      Pediatric Intensive Care Unit in shock and acute respiratory failure. The patient
      was immediately intubated, and a grayish nonadherent membrane extending through
      the glottis down into the larynx was apparent during the procedure.
      Echocardiographic findings, which were consistent with acute myocarditis,
      confirmed poor left ventricular contractility despite escalating high doses of
      inotropes. Autopsy showed numerous strains of toxigenic corynobacterium
      diphtheriae, which also grew on the Loeffler cultures of membranes received
      during the intubation. CONCLUSION: It is critical that new generations of
      clinicians and bio-pathologists not only be trained in the subspecialty of
      infectious disease pathology, but that they also be willing participants in the
      diagnosis and investigation of infectious diseases.

PMID- 15941483
TI  - Physicians perceived usefulness of high-cost diagnostic imaging studies: results
      of a referral study in a German medical quality network.
AB  - BACKGROUND: Medical and technological progress has led to increased numbers of
      diagnostic tests, some of them inducing high financial costs. In Germany, high
      cost diagnostic imaging is performed by a medical specialist after referral by a
      general practitioner (GP) or specialist in primary care. The aim of this study
      was to evaluate the physicians' perceived usefulness of high-cost diagnostic
      imaging in patients with different clinical conditions. METHODS: Thirty-four GPs,
      one neurologist and one orthopaedic specialist in ambulatory care from a Medical
      Quality Network documented 234 referrals concerning 97 MRIs, 96 CTs-scan and 41
      intracardiac catheters in a three month period. After having received the test
      results, they indicated if these were useful for diagnosis and treatment of the
      patient. RESULTS: The physicians' perceived usefulness of tests was lowest in
      suspected cerebral disease (40% of test results were seen as useful), cervical
      spine problems (64%) and unexplained abdominal complaints (67%). The perceived
      usefulness was highest in musculoskeletal symptoms (94%) and second best in
      cardiological diseases (82%). CONCLUSION: The perceived usefulness of high-cost
      diagnostic imaging was lower in unexplained complaints than in specific diseases.
      Interventions to improve the effectiveness and efficiency of test ordering should
      focus on clinical decision making in conditions where GPs perceived low
      usefulness.

PMID- 15941484
TI  - Development and evaluation of a Gal4-mediated LUC/GFP/GUS enhancer trap system in
      Arabidopsis.
AB  - BACKGROUND: Gal4 enhancer trap systems driving expression of LacZ and GFP
      reporters have been characterized and widely used in Drosophila. However, a Gal4
      enhancer trap system in Arabidopsis has not been described in the primary
      literature. In Drosophila, the reporters possess a Gal4 upstream activation
      sequence (UAS) as five repeats (5XUAS) and lines that express Gal4 from tissue
      specific enhancers have also been used for the ectopic expression of any
      transgene (driven by a 5XUAS). While Gal4 transactivation has been demonstrated
      in Arabidopsis, wide use of a trap has not emerged in part because of the lack of
      detailed analysis, which is the purpose of the present study. RESULTS: A key
      feature of this study is the use of luciferase (LUC) as the primary reporter and
      rsGFP-GUS as secondary reporters. Reporters driven by a 5XUAS are better suited
      in Arabidopsis than those containing a 1X or 2X UAS. A 5XUAS-LUC reporter is
      expressed at high levels in Arabidopsis lines transformed with Gal4 driven by the
      full, enhanced 35S promoter. In contrast, a minimum 35S (containing the TATA
      region) upstream of Gal4 acts as an enhancer trap system. Luciferase expression
      in trap lines of the T1, T2, and T3 generations are generally stable but by the
      T4 generation approximately 25% of the lines are significantly silenced. This
      silencing is reversed by growing plants on media containing 5-aza-2'
      deoxycytidine. Quantitative multiplex RT-PCR on the Gal4 and LUC mRNA indicate
      that this silencing can occur at the level of Gal4 or LUC transcription.
      Production of a 10,000 event library and observations on screening, along with
      the potential for a Gal4 driver system in other plant species are discussed.
      CONCLUSION: The Gal4 trap system described here uses the 5XUAS-LUC and 5XUAS
      rsGFP-GUS as reporters and allows for in planta quantitative screening, including
      the rapid monitoring for silencing. We conclude that in about 75% of the cases
      silencing is at the level of transcription of the Gal4 transgene and is at an
      acceptable frequency to make the Gal4 trap system in Arabidopsis of value. This
      system will be useful for the isolation and comprehensive characterization of
      specific reporter and driver lines.

PMID- 15941486
TI  - Introducing article-processing charges and inviting "detailed methods sections"
      articles.
AB  - This editorial introduces the use of article-processing charges at Epidemiologic
      Perspectives & Innovations and reviews that advantages of publishing in an Open
      Access journal. In addition, it introduces a new type of article the journal
      hopes to publish, detailed reports of study design or data analysis methods that
      have been used in health science research. The new type of article is intended to
      supplement the woefully constrained methods sections in standard research report
      articles, providing information that better fulfills the goals of scientific
      publishing.

PMID- 15941485
TI  - Stability of colon stem cell methylation after neo-adjuvant therapy in a patient
      with attenuated familial adenomatous polyposis.
AB  - BACKGROUND: Methylation at certain human CpG rich sequences increases with age.
      The mechanisms underlying such age-related changes are unclear, but methylation
      may accumulate slowly in a clock-like manner from birth and record lifetime
      numbers of stem cell divisions. Alternatively, methylation may fluctuate in
      response to environmental stimuli. The relative stability of methylation patterns
      may be inferred through serial observations of the same colon. CASE PRESENTATION:
      A 22 year-old male with attenuated familial adenomatous polyposis received neo
      adjuvant chemotherapy and radiation prior to surgery for rectal adenocarcinoma.
      Colon crypt methylation patterns before and after neo-adjuvant therapy (62 days
      apart) were essentially identical with respect to percent methylation and
      diversity. Consistent with previous studies, methylation patterns recorded no
      evidence for enhanced colon crypt stem cell survival with a germline mutation
      (codon 215) proximal to the mutation cluster region of APC. CONCLUSION: The
      inability of neo-adjuvant therapy to significantly alter crypt methylation
      patterns suggests stem cells are relatively protected from transient
      environmental changes. Age-related methylation appears to primarily reflect
      epigenetic errors in stem cells that slowly accumulate in a clock-like manner
      from birth. Therefore, life-long human stem cell histories are potentially
      written within and may be read from somatic cell epigenomes.

PMID- 15941487
TI  - Microsatellite mapping of QTL affecting growth, feed consumption, egg production,
      tonic immobility and body temperature of Japanese quail.
AB  - BACKGROUND: The Japanese quail (Coturnix japonica) is both an animal model in
      biology and a commercial bird for egg and meat production. Modern research
      developments with this bird, however, have been slowed down by the limited
      information that is available on the genetics of the Japanese quail. Recently,
      quail genetic maps with microsatellites and AFLP have been produced which open
      the way to comparative works with the chicken (Gallus gallus), and to QTL
      detection for a variety of traits. The purpose of this work was to detect for the
      first time QTL for commercial traits and for more basic characters in an F2
      experiment with 434 female quail, and to compare the nature and the position of
      the detected QTL with those from the first chicken genome scans carried out
      during the last few years. RESULTS: Genome-wide significant or suggestive QTL
      were found for clutch length, body weight and feed intake on CJA01, age at first
      egg and egg number on CJA06, and eggshell weight and residual feed intake on
      CJA20, with possible pleiotropy for the QTL affecting body weight and feed
      intake, and egg number and age at first egg. A suggestive QTL was found for tonic
      immobility on CJA01, and chromosome-wide significant QTL for body temperature
      were detected on CJA01 and CJA03. Other chromosome-wide significant QTL were
      found on CJA02, CJA05, CJA09 and CJA14. Parent-of-origin effects were found for
      QTL for body weight and feed intake on CJA01. CONCLUSION: Despite its limited
      length, the first quail microsatellite map was useful to detect new QTL for
      rarely reported traits, like residual feed intake, and to help establish some
      correspondence between the QTL for feed intake, body weight and tonic immobility
      detected in the present work and those reported on GGA01 in the chicken. Further
      comparative work is now possible in order to better estimate and understand the
      genetic similarities and differences of these two Phasianidae species.

PMID- 15941488
TI  - PAGE: parametric analysis of gene set enrichment.
AB  - BACKGROUND: Gene set enrichment analysis (GSEA) is a microarray data analysis
      method that uses predefined gene sets and ranks of genes to identify significant
      biological changes in microarray data sets. GSEA is especially useful when gene
      expression changes in a given microarray data set is minimal or moderate.
      RESULTS: We developed a modified gene set enrichment analysis method based on a
      parametric statistical analysis model. Compared with GSEA, the parametric
      analysis of gene set enrichment (PAGE) detected a larger number of significantly
      altered gene sets and their p-values were lower than the corresponding p-values
      calculated by GSEA. Because PAGE uses normal distribution for statistical
      inference, it requires less computation than GSEA, which needs repeated
      computation of the permutated data set. PAGE was able to detect significantly
      changed gene sets from microarray data irrespective of different Affymetrix probe
      level analysis methods or different microarray platforms. Comparison of two aged
      muscle microarray data sets at gene set level using PAGE revealed common
      biological themes better than comparison at individual gene level. CONCLUSION:
      PAGE was statistically more sensitive and required much less computational effort
      than GSEA, it could identify significantly changed biological themes from
      microarray data irrespective of analysis methods or microarray platforms, and it
      was useful in comparison of multiple microarray data sets. We offer PAGE as a
      useful microarray analysis method.

PMID- 15941489
TI  - Fine needle aspiration biopsy of the liver: Algorithmic approach and current
      issues in the diagnosis of hepatocellular carcinoma.
AB  - The role of fine needle aspiration biopsy (FNAB) in the evaluation of focal liver
      lesions has evolved. Guided FNAB is still useful to procure a tissue diagnosis if
      clinical, biochemical and radiologic findings are inconclusive. Major diagnostic
      issues include: (i) Distinction of benign hepatocellular nodular lesions from
      reactive hepatocytes, (ii) Distinction of well-differentiated hepatocellular
      carcinoma (WD-HCC) from benign hepatocellular nodular lesions, (iii) Distinction
      of poorly differentiated HCC from cholangiocarcinoma and metastatic carcinomas,
      (iv) Determination of histogenesis of malignant tumor, and (v) Determination of
      primary site of origin of malignant tumor. This review gives a general overview
      of hepatic FNAB; outlines an algorithmic approach to cytodiagnosis with emphasis
      on HCC, its variants and their mimics; and addresses current diagnostic issues.
      Close radiologic surveillance of high-risk cirrhotic patients has resulted in the
      increasing detection of smaller lesions with many subjected to biopsy for tissue
      characterization. The need for tissue confirmation in clinically obvious HCC is
      questioned due to risk of malignant seeding. When a biopsy is indicated, core
      needle biopsy is favored over FNAB. The inherent difficulty of distinguishing
      small/early HCC from benign hepatocellular nodular lesions has resulted in
      indeterminate reports. Changing concepts in the understanding of the biological
      behavior and morphologic evolution of HCC and its precursors; and the current
      lack of agreement on the morphologic criteria for distinguishing high-grade
      dysplastic lesions (with small cell change) from WD-HCC, have profound impact on
      nomenclature, cytohistologic interpretation and management. Optimization of
      hepatic FNAB to enhance the yield and accuracy of diagnoses requires close
      clinicopathologic correlation; combined cytohistologic approach; judicious use of
      ancillary tests; and skilled healthcare teams.

PMID- 15941490
TI  - Studies on substantially increased proteins in follicular fluid of bovine ovarian
      follicular cysts using 2-D PAGE and MALDI-TOF MS.
AB  - BACKGROUND: The objective of this study was to identify substantially increased
      proteins in bovine cystic follicular fluid (FF) in order to clarify the pathology
      and etiology of bovine ovarian follicular cysts (BOFC). METHODS: Proteins in
      normal and cystic FF samples were subjected to two-dimensional polyacrylamide gel
      electrophoresis (2-D PAGE) and were compared using silver stained gel images with
      PDQuest image analysis software. Peptides from these increased spots were
      analyzed by matrix assisted laser desorption/ionization-time of flight mass
      spectrometry (MALDI-TOF MS), and were identified based on the NCBI database by a
      peptide mass fingerprinting method. RESULTS: Comparative proteomic analysis
      showed 8 increased protein spots present in cystic FF. MS analysis and database
      searching revealed that the increased proteins in cystic FF were bovine
      mitochondrial f1-atpase (BMFA), erythroid associated factor (EAF), methionine
      synthase (MeS), VEGF-receptor, glyceraldehydes 3-phosphate dehydrogenase (GAPDH),
      heat shock protein 70 (HSP70), beta-lactoglobulin (BLG) and succinate
      dehydrogenase Ip subunit (SD). CONCLUSION: Our results suggest that these
      proteins are overexpressed in BOFC, and that they may play important roles in the
      pathogenesis of BOFC. Furthermore, these proteins in the FF could be useful
      biomarkers for BOFC.

PMID- 15941491
TI  - Molecular weight assessment of proteins in total proteome profiles using 1D-PAGE
      and LC/MS/MS.
AB  - BACKGROUND: The observed molecular weight of a protein on a 1D polyacrylamide gel
      can provide meaningful insight into its biological function. Differences between
      a protein's observed molecular weight and that predicted by its full length amino
      acid sequence can be the result of different types of post-translational events,
      such as alternative splicing (AS), endoproteolytic processing (EPP), and post
      translational modifications (PTMs). The characterization of these events is one
      of the important goals of total proteome profiling (TPP). LC/MS/MS has emerged as
      one of the primary tools for TPP, but since this method identifies tryptic
      fragments of proteins, it has not generally been used for large-scale
      determination of the molecular weight of intact proteins in complex mixtures.
      RESULTS: We have developed a set of computational tools for extracting molecular
      weight information of intact proteins from total proteome profiles in a high
      throughput manner using 1D-PAGE and LC/MS/MS. We have applied this technology to
      the proteome profile of a human lymphoblastoid cell line under standard culture
      conditions. From a total of 1 x 10(7) cells, we identified 821 proteins by at
      least two tryptic peptides. Additionally, these 821 proteins are well-localized
      on the 1D-SDS gel. 656 proteins (80%) occur in gel slices in which the observed
      molecular weight of the protein is consistent with its predicted full-length
      sequence. A total of 165 proteins (20%) are observed to have molecular weights
      that differ from their predicted full-length sequence. We explore these molecular
      weight differences based on existing protein annotation. CONCLUSION: We
      demonstrate that the determination of intact protein molecular weight can be
      achieved in a high-throughput manner using 1D-PAGE and LC/MS/MS. The ability to
      determine the molecular weight of intact proteins represents a further step in
      our ability to characterize gene expression at the protein level. The
      identification of 165 proteins whose observed molecular weight differs from the
      molecular weight of the predicted full-length sequence provides another entry
      point into the high-throughput characterization of protein modification.

PMID- 15941492
TI  - Low-resolution electromagnetic tomography and treatment response in obsessive
      compulsive disorder.
AB  - We investigated whether findings from pretreatment low-resolution electromagnetic
      tomography (LORETA) predicted response to drug treatment in patients with
      obsessive-compulsive disorder (OCD). The 3D intra-cerebral distribution of
      neuronal electrical activity from the scalp-recorded potential distribution of 17
      drug-free patients with OCD was assessed with LORETA. They were treated with
      antidepressants in the maximum tolerated doses for at least 12 wk. Individuals
      were considered to be treatment responders if they displayed a reduction of at
      least 35% on the initial YBOCS scores and had a final CGI score of 1 or 2. The
      SPM-99 t test for independent samples was employed to compare, voxel-by-voxel,
      the brain electrical activities of responders (n = 10) and non-responders (n =
      7). Responders exhibited significantly lower activities in beta band in the
      rostral anterior cingulate [Brodmann's area (BA) 24 and 32] (p = 0.002) and the
      medial frontal gyrus (BA 10) (p = 0.002), suggesting that a distinctive pattern
      of activity within the medial surface of the frontal lobe predicts therapeutic
      response in OCD.

PMID- 15941493
TI  - Conditioned rewarding stimulus associated with cocaine self-administration
      reverses the depression of catecholamine brain systems following cocaine
      withdrawal in rats.
AB  - Craving phenomena are related to induction of substance-seeking behaviour by
      stimuli associated with the availability of the drug. We investigated the changes
      in monoamine metabolism in regions of the brains of rats that, following a period
      of training of cocaine self-administration, were either killed 2 h after the last
      session or underwent extinction trials, during which cocaine was withdrawn.
      During the training, acoustic and visual stimuli announced the availability of
      cocaine. After 10 d of daily extinction trials, rats were re-introduced into the
      cage, and a signal associated with cocaine availability was applied to half of
      the animals. The rats were immediately killed and concentrations of dopamine and
      serotonin and their metabolites in various brain areas, and the concentration of
      noradrenaline and MHPG in the brainstem were assessed to calculate their
      metabolism rate indices. In rats self-administering cocaine, the levels of
      metabolites of all three amines were depressed, indicating a depression of the
      activity of monoaminergic systems. In the period of extinction, the dopamine
      levels in the nucleus accumbens and striatum and the level of the noradrenaline
      metabolite, MHPG, in the brainstem were reduced, suggesting a long-lasting
      disturbance of the catecholaminergic system, while serotonin levels and
      metabolism returned to normal values. The presence of the signal associated with
      previous cocaine availability, which invariably caused the reinstatement of
      cocaine-seeking behaviour annulled the changes observed in the group receiving no
      stimulus, bringing the concentration values of dopamine, and dopamine and
      noradrenaline metabolites to yoked-saline control rats. The results suggest that
      the stabilized self-administration of cocaine depresses the activity of all
      biogenic amine systems, and the changes in serotonin system are reversible, in
      contrast to those observed in catecholaminergic systems, which show the signs of
      a long-lasting impairment. The stimulus associated with cocaine availability
      activates the catecholaminergic system in animals after extinction procedure.

PMID- 15941494
TI  - Gene expression of tryptophan hydroxylase 2 in post-mortem brain of suicide
      subjects.
AB  - The tryptophan hydroxylase isoform-2 gene (TPH2) is located on chromosome 12 and
      is expressed primarily in brain tissue. While genetic association and mRNA
      expression studies implicate the tryptophan hydroxylase isoform-1 gene (TPH1) in
      depression and suicidality, the TPH1 gene is 150-fold less expressed in mouse
      brain than TPH2. We hypothesized that completed suicide is associated with
      abnormal TPH2 expression in the brain. TPH2 and beta-actin mRNA levels were
      measured in post-mortem brain using quantitative real-time PCR. mRNA samples
      provided by the Stanley Foundation Array Collection were derived from the
      dorsolateral prefrontal cortex (Brodmann Area 46) of 23 completed suicides and 23
      control subjects. There is no difference in the mRNA levels between the suicide
      group and non-suicide group (p = 0.69). Although greater amounts of TPH2 mRNA
      were found in the suicide group, this difference was not significant. Further
      investigation of TPH2 gene expression is needed to clarify the potential role of
      this gene in the pathophysiology of suicide.

PMID- 15941495
TI  - [To develop a model on severe acute respiratory syndrome epidemics to
      quantitatively evaluate the effectiveness of intervention measures].
AB  - OBJECTIVE: To build an epidemic model of severe acute respiratory syndrome (SARS)
      to be used to quantitatively evaluate the effectiveness of intervention measures.
      METHODS: Following the nature of SARS epidemics, an epidemic model of SARS based
      on SEIR model of infectious disease was built, in which case management group was
      set up and some parameters related to control measures were included. As an
      example, data gathered from Beijing was fitted to illustrate its application to
      quantitatively evaluate the intervention measures. RESULTS: In the newly
      developed model of epidemics, parameters related to control measures could easily
      be modified. When scenario assumption was used, a model on SARS outbreak under
      various circumstances of intervention measures could be set. Thus, quantitative
      evaluation of intervention measures could perfectly be caried out. Pilot study
      revealed that the fitness existed in modeling the outbreak of SARS in Beijing and
      the intervention measures implemented around April 20, 2003, had major
      contribution to the control of SARS. CONCLUSION: The model of SARS epidemics
      seemed to be stable and reliable to be used to evaluate the effectiveness of
      intervention measures implemented during the SARS outbreak in a quantitative way.

PMID- 15941496
TI  - [The application of a systematic-dynamic model to study the computer simulation
      of severe acute respiratory syndrome transmission and the impact of control
      measures].
AB  - OBJECTIVE: (1) Building a macroscopical systematic-dynamic model of severe acute
      respiratory syndrome (SARS) transmission and disease control process. (2) To
      determine key variables on the control of SARS epidemic through computer
      simulation methodology, especially to analyze the effect of "screening for fever"
      practice during the epidemics. (3) To provide evidence for related decision
      making. METHODS: Parameters in the model were collected from local hospitals and
      municapal CDC through interview, questionnaire survey, literature review and case
      analysis. A systematic-dynamic model was built under similar studies. 'What-if'
      analysis was used during the simulation process. RESULTS: (1) The mean duration
      between disease onset and hospital admission, rate of contacts of each infectious
      individual as well as the rate of contacts in hospital of each infectious
      individual appeared to be the key variables in the process of SARS transmission.
      (2) Physician's alertness/sense and practice of self-protection on SARS, measures
      on quarantine and isolation to the patients, ventilation and disinfection process
      in the wards appeared to be the key variables for the control of epidemics. (3)
      "Screening for fever" practice on each patient at the entrance of the hospital
      did not seem to act as an important factor to the control of the epidemics.
      CONCLUSION: The health system in Beijing can control SARS epidemic rapidly based
      on current applied disease control measures and plan.

PMID- 15941497
TI  - [Analysis on the multi-distribution and the major influencing factors on severe
      acute respiratory syndrome in Beijing].
AB  - OBJECTIVE: To analyse the multi-dimension nature of severe acute respiratory
      syndrome (SARS) transmission. METHODS: Based on the data of SARS in 2003 and the
      geographic information system of Beijing, as well as under the broad range of the
      theorems and techniques of data-driven and model-driven knowledge mining,
      hierarchical techniques were used to test the hot spots. Wavelet technique was
      also used to decompose Moran's I frequency to survey the spatial clustering
      process of SARS. For factors analysis, BW test was used to distinguish factors
      which influencing SARS process. In temporal aspects, susceptive-infective-removal
      model (SIR) without Taylor expansion was solved by a genetic-simulated annealing
      algorithm, that directly provided a new approach to obtain epidemic parameters
      from the SIR model. RESULTS: Different order of spatial hot spots were noticed
      and the clustering were relevant with the means of transportation. Diffusion
      dynamics were changed along with the temporal process of SARS. Regarding factor
      analysis, geographic relationship, population density, the amount of doctors and
      hospitals appeared to be the key elements influencing the transmission of SARS.
      The predictable number of SARS cases evolving with time were also calculated.
      CONCLUSIONS: Cluster detection of close contacts of SARS infective in Beijing
      revealed the spatial characters of urban population flow and having important
      implications in the prevention and control of this communicable diseases. Some
      human and physical environment factors played statistical significant roles in
      different periods during SARS epidemics. An efficient algorithm was developed to
      solve SIR model directly, enabling the estimation of epidemic parameters from SIR
      and early forecast.

PMID- 15941499
TI  - [Survey on the situation of antenatal care in different regions of China, in 1971
      - 2003].
AB  - OBJECTIVE: To comprehensively understand the situation of antenatal care in the
      last thirty years and to identify the existing problems and challenges. METHODS:
      PPS method was used to select those women under study and face to face interview
      was carried out at the house. RESULTS: The quality and coverage rate of antenatal
      care as well as the rate of hospital delivery had been continuously increasing
      over time and the coverage rate of antenatal checkup had increased from 38.7% in
      1970s to 95.9%, while the institutional delivery rose from 20.1% to 87.4% in the
      last three years. However, problems and challenges were found refering to the of
      delay first antenatal care, inadequate timing and with incomplete contents. Only
      71.7% of the pregnant women had received first checkup during the first three
      months. 64.1% of the women received 5 times or more of the checkups while only
      29.1% of the women had received all the 7 basic checkup items. Rate of hospital
      delivery was unsatisfactory that most (79.5%) of the women had the delivery not
      in the hospitals when under the assistance of midwife/village doctors. Indicators
      showed that the worst was in the western regions. CONCLUSION: Great progress had
      been made in the field of antenatal care in last thirty yeats in China. The
      coverage rate of antenatal checkup and institutional delivery had been improved.
      But the quality of antenatal care should be further improved, especially in the
      western regions.

PMID- 15941501
TI  - [Assessment on nutritional status among children under 3 years using
      anthropometry in 40 counties of western China].
AB  - OBJECTIVE: To assess nutritional status among children younger than 3 years in 40
      counties of western China, using anthropometry. METHODS: With cross-sectional
      study and random sampling, a survey with a sample size of 7252 was conducted in
      40 counties of western China on children under 3 years old. Height and weight
      were measured and nutrition status was evaluated with WHO/NCHS reference using Z
      scores. RESULTS: SD of height for age (HA) and weight for age (WA) were 1.10 -
      1.30 and 1.06 - 1.40, respectively and SD of WAZ for infants varied. The
      distribution of HA Z and WAZ shifted downward to 1 unit and 0.4 unit for
      distribution of weight for height (WHZ). The prevalence of stunting, underweight
      and wasting were 23.0%, 22.6% and 7.5% respectively. The prevalence rates were
      low among those yourger than 3 months. Stunting and underweight increased sharply
      after 6 months and reached 20% - 30%. Significant correlation was found between
      underweight and stunting or wasting with coefficients of 0.815 and 0.636,
      respectively. No correlation was found between stunting and wasting. CONCLUSION:
      The nutrition status adversely affected children as a whole but not only for
      individuals. There was a higher prevalence of malnutrition mainly on low height
      to children. Weight for age must be interpreted cautiously because of the
      inability of this indicator in distinguishing stunting and wasting just by
      itself. Assessment by anthropometry called for accurate information on age and
      measurement of height and weight.

PMID- 15941503
TI  - [Epidemiological investigation on congenital heart disease in several regions of
      Yunnan province].
AB  - OBJECTIVE: To investigate the distribution of congenital heart disease (CHD) aged
      3 - 18 in several regions of Yunnan province. METHODS: Cross-rectional studies
      were carried out among 48 638 children from Xishuangbanna, Dali, Baoshan
      Longling, Luxi Mangshi and Gejiu in Yunnan province with stratified, clustered
      sampling. RESULTS: The overall morbidity of CHD was 5.08 per thousand with 5.09
      per thousand in males and 5.07 per thousand in females. Morbidity rates in
      different regions were 2.75 per thousand in Xishuangbanna, 7.85 per thousand in
      Dali, 9.59 per thousand in Baoshan Long ling, 4.80 per thousand in Gejiu, 16.99
      per thousand in Luxi Wuchalu. However, in the same area, rates were different
      among different residents:3.25 per thousand in Gejiu, and was 9.10 per thousand
      in Laochang stannum mine, 11.20 per thousand in Datunxuanchang; 5.74 per thousand
      at the city of Baoshan Longling, 11.35 per thousand at countryside; 4.90 per
      thousand at the city of Dali, 8.71 per thousand at countryside; 1.69 per thousand
      at the city of Xishuangbanna, 4.40 per thousand at country. Morbidity rates in
      different ethnic groups were as follows: 5.39 per thousand in Dai, 6.83 per
      thousand in Jinuo, 0 per thousand in Hani, 8.12 per thousand in Bai, 14.18 per
      thousand in Jingpo. CONCLUSION: There were significant regional and ethnic
      differences seen in Yunnan on the mobidity of CHD which was different from the
      domestic literature reported.

PMID- 15941505
TI  - [Application of SF-36 scale on pulmonary tuberculosis patients in Yunnan province
      of China and southern Thailand].
AB  - OBJECTIVE: To explore the effect of SF-36 scale being applied in different
      countries under different culture and to describe the quality of life of
      pulmonary tuberculosis patients in China and Thailand. METHODS: SF-36 scale was
      applied to pulmonary tuberculosis patients in both countries using face to face
      interview. RESULTS: Many coefficients among domains were greater than 0.5 when
      quality of life of tuberculosis patient in both countries was measured.
      Cronbach's coefficient of all domains were greater than 0.7 for tuberculosis
      patients in China while cronbach's Coefficient of most domains were equal or
      greater than 0.7 for tuberculosis patients in Thailand except for vitality and
      social domains. The score of social domain for patients in Thailand was greater
      than that of China. CONCLUSION: Structure validity was not good for tuberculosis
      patients in both countries since there were some items overlapped in different
      domains. However, the reliability was good for measuring quality of life of
      tuberculosis patients both in China and in Thailand.

PMID- 15941506
TI  - [An 1-year prospective cohort study on mortality of injecting drug users].
AB  - OBJECTIVE: To study the mortality among injecting drug users (IDUs) from an IDUs
      cohort in Liangshan of Sichuan province. METHODS: In November 2002, 376 injecting
      drug users were recruited and followed up for 1 year as part of a prospective
      cohort study. Socio-demographics and risk behaviors on drug use were recorded.
      After one year, the mortality rate was estimated and risk factors for mortality
      were analyzed using Cox regression. RESULTS: Out of the original cohort of 376
      participants, there were 28 reported and confirmed deaths during the one year
      follow-up period. The mortality rate of the cohort was 77.32 per 1000 person
      years (95% CI: 48.68 - 105.95) with the standardized mortality ratio (SMR) as
      47.62 (95% CI: 31.63 - 68.71). Out of the 28 deaths, 64.3% (18/28) caused by
      overdoses of drug. No variables were found to be associated with death of all
      causes, but being un-married and >or= 9 year history of injecting drugs were
      found to be associated with overdose-related mortality in the final model of Cox
      regression. The hazard ratios were 4.51 (95% CI: 1.03 - 19.67) and 2.77 (95% CI:
      1.10 - 7.00) respectively. CONCLUSION: Overdose served the most frequent cause of
      deaths in Liangshan of Sichuan province. Future studies should be conducted to
      focus on mortality and risk factors associated with mortality among IDUs to
      provide targeted interventions in reducing unnatural mortality.

PMID- 15941507
TI  - [Study on the dynamics of IgG antibody in 311 patients with severe acute
      respiratory syndrome].
AB  - OBJECTIVE: To detect the level and dynamic change of severe acute respiratory
      syndrome (SARS)-coronavirus-specific IgG antibody in conavalescent SARS patients,
      and to provide information for prevention and vaccine development. METHODS: IgG
      antibody against coronavirus was detected by ELISA in the blood of 311
      convalescent SARS patients for every 2 - 4 weeks. Stata 7.0 statistics software
      was used to analyse the results. RESULTS: IgG antibody was detected positive on
      each testing of all the convalescent patients and its peak appeared 35 days after
      recovery. IgG antibody level showed a 35.8% decrease within one year. CONCLUSION:
      Data showed that all the SARS convalescent patients had generated high level of
      specific IgG antibody against coronavirus in the early stage of recovery, but the
      antibody level declined along with the progress of convalescence, suggesting that
      the detection of the IgG antibody should go on until it disappeared.

PMID- 15941509
TI  - [Study on the validation of the computer science application's activity monitor
      in assessing the physical activity among adults using doubly labeled water
      method].
AB  - OBJECTIVE: Using doubly labeled water method to validate the colmputer science
      application's activity monitor (CSA) in assessing physical activity of free
      living adults in Beijing, in order to develop equations to predict total daily
      energy expenditure (TEE) and activity related energy expenditure (AEE) from
      activity counts (AC) and anthropometric variables. METHODS: A total of 72 healthy
      adults (33 males and 39 females, mean age 43.6 +/- 4.0 yr) were monitored for 7
      consecutive days by CSA. TEE was simultaneously measured using doubly labeled
      water method. Average AC (counts/min(-1)) was compared with TEE, AEE and physical
      activity level (PAL). RESULTS: Physical activity determined by AC was
      significantly related to data on energy expenditures: TEE (r = 0.31, P < 0.01),
      AEE (r = 0.30, P < 0.05), and PAL (r = 0.26, P < 0.05). Multiple stepwise
      regression analysis showed that TEE was significantly influenced by gender, fat
      free mass (FFM) or BMI and AC (R(2) = 0.52 - 0.70) while AEE was significantly
      influenced by gender, FFM and AC (R(2) = 0.25 - 0.32). CONCLUSION: AC from CSA
      activity monitor seemed a useful measure in studying the total amount of physical
      activity in free-living adults while AC significantly contributed to the
      explained variation in TEE and AEE.

PMID- 15941510
TI  - [Study on the RNA of severe acute respiratory syndrome (SARS) associated
      coronavirus in the blood and excretion of convalescent patients with SARS].
AB  - OBJECTIVE: To examine the RNA of severe acute respiratory syndrome-associated
      coronavirus (SARS-CoV) in the blood and excretion of convalescent patient with
      SARS for prevention and treatment of the disease. METHODS: A total of 276
      samples, including plasma, urine, feces and sputum, obtained from 23 convalescent
      patients with SARS were studied at 3 time-points at least 21 days after the onset
      of symptoms. RNA was extracted and nested reverse transcription-polymerase chain
      reaction (RT-PCR) was carried out using SARS-CoV specific primers. RESULTS: Among
      the 276 samples, SARS-CoV RNA was detected in 6 cases (38.8%) by nested RT-PCR.
      The positive rates of SARS-CoV RNA was 5.8% in feces and 2.9% in sputum samples
      but SARS-CoV RNA was not detectable in plasma and urine of all the cases.
      CONCLUSION: The existence of SARS-CoV RNA in the excretion of some convalescent
      patients with SARS showed that the excretion from these patients should be
      carefully treated whilthe re-transmission of SARS by which, should be further
      studied.

PMID- 15941511
TI  - [Survival and growth of Vibrio cholerae O139 inside Acanthamoeba].
AB  - OBJECTIVE: To study the survival and growth of Vibrio cholerae inside the
      Acanthamoeba polyphage. METHODS: Survival and growth of Vibro cholerae O139, co
      cultured with Acanthamoeba polyphaga, was observed inside the trophozoites and
      cysts, using Gram stain and electron microscope. RESULTS: Viable O139 was
      observed inside the amoebal vacuoles in 24 hours. Vacuoles were filled with more
      bacteria along with the longer period of co-culture. The process of O139
      infection with Amoebae would include uptake, formation of O139 vacuole,
      multiplication, trophozoites lysed and expel under electron microscopy. Some
      infected trophozoites could subsequently encyst and the surviving O139 could
      locate in the vesicles inside the cysts. CONCLUSION: O139 might survive and
      multiply in the trophozoites and reside inside the cysts of Amoebae, suggesting
      that Acanthamoebae might serve as one of the environmental hosts of Vibro
      cholerae.

PMID- 15941512
TI  - [Studies on the germination of Bacillus anthracoides spores induced by nutrient
      germinant].
AB  - OBJECTIVE: To explore the germination effects of Bacillus anthracoides spores
      germinant to nutrient germinant. METHODS: Heat factors and nutrient germinant
      were used to stimulate the Bacillus anthracoides spores and to germinate.
      Ultraviolet spectrophotometer was used to measured the A value of spore solution
      in the wavelength of 600 nm. Accrding to the A value, the germination rates in
      different condition. Transmission electron microscope was used to observe the
      ultrastructure changes of spores. RESULTS: The rate of germination effects were
      68.0% under 6 mmol/L inosine at 37 degrees C, pH 7.9; 74.5% under 70 mmol/L L
      alanine at 30 degrees C, pH 8.9; and 85.6% under 6 mmol/L inosine and 70 mmol/L L
      alanine at 37 degrees C, pH 8.2. Under transmission electron microscope, the
      germinated spores' coat and cortex were brokendown and degraded with its core
      completely exposed. CONCLUSION: Under suitable environment, the nutrient
      germinant with inosine and L-alanine might be helpful for germinating the
      bacillus anthracoides spores.

PMID- 15941513
TI  - [Study on the prevalence rate of chronic obstructive pulmonary disease in
      northern part of Guangdong province].
AB  - OBJECTIVE: To investigate the prevalence of chronic obstructive pulmonary disease
      (COPD) and its risk factors in population over 40 years old in northern part of
      Guangdong province. METHODS: Using uniform scheme, procedures and questionnaire,
      a cluster-randomized-sampling survey for the population aged over 40 years in a
      rural area of Shaoguan in the northern part of Guangdong province was performed.
      Spirometry was performed for every participant, followed by a bronchodilatation
      test when bronchial obstruction was present. RESULTS: There were 1468 cases with
      complete data from 1498 people aged >or= 40 years including 640 males, 828
      females with an average age of 54.3 years old. The total prevalence of COPD was
      12.0%. The prevalence of COPD in males was significantly higher than that in
      females (18.3% vs. 7.1%, P < 0.01). Only 80.7% of the patients with COPD
      presented one or more symptoms as cough, phlegm, or dyspnoea. Underdiagnosis of
      COPD would be quite serious. Only 26.1% of the cases was previously diagnosed to
      have chronic bronchitis, emphysema, or COPD. Smoking was an important risk factor
      to COPD and 78.4% of the patients with COPD were smokers. However, relation of
      biomass and COPD called for further investigation. CONCLUSION: Prevalence of COPD
      was much higher than expected in the northern part of Guangdong while smoking was
      an most important risk factor of COPD. Lung function test seemed to be of great
      importance to COPD diagnosis, especially in the earlier period of COPD.

PMID- 15941514
TI  - [Study on the prognostic factors of colorectal cancer after radical resection and
      on suggested model for prediction].
AB  - OBJECTIVE: To study the factors of colorectal cancer (CRC) after radical
      resection to provide data predicting the prognosis of the patients. METHODS: 120
      cases of CRC were collected in this study. Medical clinical records and 5-year
      follow-up data were reviewed. Streptavidin-peroxidase immunohistochemical
      technique was used to detect the expression of p53, C-erbB-2, nm23-H(1) and Ras
      on formalin-fixed, paraffin embedded sections of CRC from the 120 patients.
      RESULTS: Results showed that the rates of positive expression of p53, C-erbB-2,
      Ras and nm23-H(1) were 62.5% (75/120), 25.8% (31/120), 80.0% (96/120) and 60.8%
      (73/120) respectively in the CRC tissue. All pathological variables and
      biological markers were analyzed with Cox regression model (alpha = 0.05). Eight
      distinguished prognostic factors were identified in the univariate analysis as:
      macroscopic configuration, histology grade, depth of invasion of intestinal,
      lymph nodes metastasis, Dukes' classification, p53, Ras and nm23-H(1). The
      results of multivariate analysis (alpha = 0.05) indicated that the independent
      prognostic factors were Dukes' classification, p53 and nm23-H(1) (P = 0.000),
      with relative risk of 3.06, 6.02 and 0.40, respectively. A prognostic model: h(t,
      x) = h(0)(t)exp (-0.9269X(14) + 1.1197X(10) + 1.7948X(11)) was established.
      Sensitivity, specificity agreement and reliability of the model and Kappa were
      79.1%, 83.0%, 80.8% and 0.62, respectively. CONCLUSION: Dukes' classification,
      p53 and nm23-H(1)seemed to be independent and important prognostic factors. This
      prognostic model could be used to evaluate the prognosis of patients with CRC by
      clinicians.

PMID- 15941515
TI  - [A connection number-based principal factor analysis forecast method to forecast
      the encephalitis B epidemics].
AB  - OBJECTIVE: To detect the relations between incidence rate of the epidemical
      encephalitis B and related factors, to provide a simple, valid and practical new
      method for forecasting encephalitis B eipdemics. METHODS: Connection number
      between the incidence rate of encephalitis B and the historical forecast factors
      was computed, before ranking the first, second and the third principal factor, to
      remove the factor with the smallest value in the light of the connection number
      before comparing the newest value of forecast factors with the same kind of
      history while the most nearly value becoming the forecasting factor value and to
      establish a forecasting equation according to the factor value and the consistent
      degree of the incidence rate of encephalitis B at that time. Finally, to put into
      the new factor value to get this forecast value under this equation. Assuming
      that there are n' (n' >or= 2) forecast factors, this time forecast value can then
      be directly obtained from the average of these estimate values. RESULTS: Using
      above forecast method to forecast the incidence rate of encephalitis B at certain
      place and year, the predicting value is very much close to the actual incidence
      rate. Difference between the predicting value forecasted by the above-mentioned
      method and the actual incidence rate is only 0.0264/100 000 with an accurate rate
      of 97.94%. CONCLUSION: This principal factor analysis forecast method based on
      connection number in forecasting the incidence rate of encephalitis B prevention
      is acceptable.

PMID- 15941522
TI  - [Study on the current status and priority of hepatitis B virus intrauterine
      infection].

PMID- 15941524
TI  - [A retrospective study on the association of sexual behavior during pregnancy
      with intrauterine infection of hepatitis B virus].
AB  - OBJECTIVE: Case-control study was employed to explore the association of sexual
      behavior during pregnancy and hepatitis B virus (HBV) intrauterine infection.
      METHODS: 212 HBsAg positive pregnant women were consecutively collected and
      investigated as objects. Those neonates detected for HBsAg with S/N value > or =
      5 by Abbott reagents in periphery sera were selected as cases, others as
      controls. Information on sexual behavior during pregnancy, maternal HBeAg status
      and other factors was collected, and were analyzed with univariate analysis,
      multivariate logistic regression analysis, etc, to explore the association of
      factors with HBV intrauterine infection. RESULTS: Ten of the 214 neonates were
      validated as occurrence of HBV intrauterine infection. Sexual behavior in the
      second trimester during pregnancy, with odd ratios 9.15 (95% CI: 1.10 - 76.28),
      as well as maternal positivity for HBeAg and HBV DNA, was significantly
      associated with HBV intrauterine infection, and sequently affirmed by multiple
      logistic regression analysis. The strength of association increased with
      frequency of sexual behavior. Interaction analysis suggested that there was
      synergistic interaction between maternal positivity of HBeAg and sexual behavior
      in the second trimester. CONCLUSION: Sexual behavior was a newly discovered risk
      factor for HBV intrauterine infection, which need to be estimated in future
      studies. Inhibition of virus replication and moderate control of sexual behavior
      would be helpful to prevent HBV intrauterine infection.

PMID- 15941526
TI  - [Study on the relationship between fetomaternal cellular traffic and hepatitis B
      virus intrauterine infection].
AB  - OBJECTIVE: To study the relationship between fetomaternal cellular traffic and
      hepatitis B virus (HBV) intrauterine infection. METHODS: Maternal DNA and fetal
      DNA were amplified by short tandem repeat (STR)-polymerase chain reaction (PCR),
      allele-specific PCR (As-PCR) and heminested PCR (hemi-nPCR). Cell transfer from
      mother-to-fetus or fetus-to-mother was determined by detecting the existence of
      TH01, GSTM1 and ACE. The relationship between cell transfer from mother-to-fetus
      and HBV intrauterine infection was analyzed by nested case-control study.
      RESULTS: 26 of the 42 informative mother-baby pairs indicated mother-to-fetus
      cell traffic, 32 of the 40 informative mother-baby pairs indicated fetus-to
      mother cell traffic and two-way cell traffic occurred in 10 mother-baby pairs.
      Statistical analysis demonstrated that the mother-to-fetus instead of fetus-to
      mother cell traffic presented the association with HBV intrauterine infection.
      There was no significant correlation between mother-to-fetus cell traffic or the
      fetus-to-mother cell traffic. Both mother-to-fetus cell traffic and PBMC HBV DNA
      positivity appeared in pregnant women were risk factors of HBV intrauterine
      infection but the two did not manifest the interaction. The positive risk factors
      of positivity PBMC HBV DNA in newborns would included mother-to-fetus cell
      traffic and PBMC HBV DNA in pregnant women, also did not display the interaction.
      CONCLUSION: The cell traffic from HBsAg positive mother to fetus had more
      contribution to HBV intrauterine infection, which was possibly one of the HBV
      routes of intrauterine infecting.

PMID- 15941525
TI  - [Relationship between cytokine gene polymorphism and susceptibility to hepatitis
      B virus intrauterine infection].
AB  - OBJECTIVE: To explore the possible relationship between cytokines (TNF-alpha, IFN
      gamma, IL-4 and IL-10), which were expressed abnormal quantity in the peripheral
      blood to intrauterine HBV infectious children, gene single nucleotide
      polymorphism (SNP) and susceptibility to HBV intrauterine infection. METHODS: A
      cross sectional study on molecular epidemiology was carried out. The subjects
      were selected from outpatients of the hepatitis B vaccine special clinics of our
      hospital. According to intrant criteria, children under high risk of HBV
      intrauterine infection were divided into immuno-failure group (group I) and
      immuno-effective group (group II) while children without high risk were included
      in the control group. Four gene SNP sites of TNF-alpha-238, IFN-gamma + 874, IL-4
      590 and IL-10-1082 region were determined by real-time quantitative fluorescent
      PCR. RESULTS: Significant differences of TNF-alpha-238 A allele frequency were
      found between group I and group II (chi(2) = 6.797, P < 0.05) as well as between
      group I and control group (chi(2) = 9.513, P < 0.05). No evident difference of
      TNF-alpha-238 A was found between group II and control group (chi(2) = 0.047, P >
      0.05). Significant differences of IFN-gamma + 874 A allele frequency were found
      between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and
      the controls (chi(2) = 5.199, P < 0.05) but no significant difference was found
      between group II and control group (chi(2) = 0.602, P > 0.05). Significant
      differences of IL-4-590 C/T allele frequency were not found between group I and
      group II (chi(2) = 0.632, P > 0.05), group I and control group (chi(2) = 0.584, P
      > 0.05), or between group II and control group (chi(2) = 0.004, P > 0.05)
      respectively. Significant differences of IL-10-1082 G allele frequency were found
      between group II and group I (chi(2) = 10.359, P < 0.001), and between group II
      and the controls (chi(2) = 35.418, P < 0.001), but not found between group I and
      control group (chi(2) = 1.759, P > 0.05). CONCLUSION: This study suggested the
      possibility that TNF-alpha-238 A allele and IFN-gamma + 874 A allele were
      associated with HBV intrauterine infection. There was no evident relationship
      between IL-4-590 C/T allele SNP and susceptibility to HBV intrauterine infection,
      but the IL-10-1082 G allele seemed to be associated with preventive efficacy to
      HBV intrauterine infection.

PMID- 15941528
TI  - [Study on diet, physical activities and body mass index in Chinese population in
      2002].
AB  - OBJECTIVE: To describe the prevalence of behavior on diet, physical activities
      and body mass index (BMI) in different populations related to factors as
      education, occupation and geographical distribution. METHODS: Indicators
      including frequency of taking different foods, intake of cooking oil/fast foods,
      intensities of physical activities at work, proportion of taking physical
      exercises during the day, sedentary life style and BMI were calculated based on
      results from 17 questions of behavior risk factors surveillance (BRFS)
      questionnaire by weight on age structures from 2000 census. RESULTS: Seventy
      percentage of the people took vegetable and 40 percent took fruits 5-7 days per
      week, and over 50 percent of them ate pork/beef/mutton but few of them ate beans
      and eggs. 25 percent of the people ate chicken/duck/fish/and shrimps 5-7 times
      per week but another 40 percent ate them only less then once per week. 70% of the
      people almost never drank milk or milk-products. 15 percent of them consumed
      sweet and greasy foods 3-7 days per week and 30 percent of them ate smoked food 3
      7 days per week in the past 30 days. The proportions of food intake were
      different under different geographical regions, education levels and occupations.
      11.7% of the sample population cooked mainly with animal oil, and 33% of the
      students had ever been to McDonald's. 11.7%, 20.5%, 44.7% and 23.0% of the
      subjects engaged in sedentary, light, moderate or heavy physical activities
      respectively. 18.04% of the subjects took part in physical exercises with
      different proportions by gender, occupation, education and geographical settings.
      8.3% people were slim which was defined as having BMI lower than 18.5 kg/m(2).
      68.0% of the people had a BMI as 18.5-23.9 kg/m(2). 23.7% of the subjects were
      being overweight which was defined as having BMI greater than 24 kg/m(2), among
      which 8.5% people with a BMI of 24-24.9 kg/m(2). CONCLUSION: The prevalence of
      overweight and obesity will increase in the next 20-30 years, with the habits of
      taking more foods with high fat and energy but with less physical activities and
      keeping the idea as "fattier makes happier". Priorities should be given to
      changing the diet habit, avoiding over-intake of high fat and high energy plus
      increasing physical activities through publicity of knowledge on health, policy
      enforcement and development of supportive environment.

PMID- 15941530
TI  - [Prevalence of major external birth defects in high and low risk areas in China,
      2003].
AB  - OBJECTIVE: To study the prevalence rates of birth defects in high and low risk
      areas in China. METHODS: A population-based surveillance system on birth defects
      was used to obtain the prevalence rates of 24 kinds of major external birth
      defects from > or = 20 weeks of gestation to 7 days of life in selected areas in
      Shanxi and Jiangsu provinces. RESULTS: The birth prevalence of birth defects
      (232.4 per 10,000 births) and neural tube defects (NTDs) (138.7 per 10,000
      births) in four counties of Shanxi province were significantly higher than that
      in Taiyuan city (75.3 and 28.2 per 10,000 births, respectively). There was no
      significant difference for all selected birth defects between Wuxi city and
      Xishan counties in low risk areas. There was a 6.1-fold of higher prevalence for
      NTDs in Taiyuan city compared with that in Wuxi areas (4.6 per 10,000 births). In
      four counties of Shanxi province, the prevalence rates of anencephaly, spina
      bifida, hydrocephaly, cleft palate alone and polydactyly were significantly
      higher than in Wuxi areas. The NTDs prevalence rate in four counties of Shanxi
      was 30.2 times higher than in Wuxi areas. When compared with previous
      surveillance data, the NTDs prevalence rate did not present obvious declining
      trend in high risk areas. The birth prevalence rate had a 31.8% decrease when
      births were calculated after 28 gestational weeks and compared with those from 20
      gestational weeks. CONCLUSION: NTDs remained to be the most common birth defect
      seen in Shanxi province. The birth prevalence rate of NTDs in some areas of
      Shanxi province was among the highest that ever reported in the world in
      comparison with data from other countries and regions. The current prevalence
      rate in high risk areas in Shanxi province did not clearly show a declining
      trend. Programs on surveillance and prenatal diagnosis were proved to have made
      big impact on the rates of major external birth defects.

PMID- 15941532
TI  - [Study on the current situation and influential factors of child neglect among
      aged 3-6 year-olds in the urban areas of China].
AB  - OBJECTIVE: Children aged 3 - 6 years in the urban areas of China were surveyed
      for the first time to find out the state of child neglect (CN) as well as the
      major relevant risk factors so as to provide evidence for developing intervention
      measures. METHODS: 1163 children (of whom 49.6% were males and 4.5% were minority
      nationality) were randomly sampled under multistage stratification, from 25
      cities which representing 15 provinces of China. Based on the Child Neglect Norms
      used by China, prevalence of CN was identified and SPSS-Windows 11.0 was employed
      for statistical analysis. Scores, frequency/degrees, age, sex and 5 types
      (physical, emotional, educational, medical and safety) of CN on every group of
      the regions, were calculated. Multifactorial analysis was conducted through
      Binary Logistic Regression and multiple linear regression to determine the
      relevant risk factors. RESULTS: (1) The average degree of CN for the 3 - 6 year
      olds was 42.2, with its prevalence as 28.0%. Degrees of CN for the groups of 3,
      4, 5, 6-year-olds were 41.7, 42.2, 42.1 and 43.1 (F = 0.988, P > 0.05), with
      frequencies of 25.0%, 25.3%, 27.9% and 35.4% (chi(2) = 4.798, P > 0.05),
      respectively. Degrees for CN in males and females were 42.7 and 41.8 (F = 2.502,
      P > 0.05) with the frequencies as 32.6% and 23.7% (chi(2) = 6.585, P < 0.05),
      respectively. Degrees of CN for the five types were 39.4-43.4 with the
      frequencies as 5.1%-12.9%, respectively. No significant difference was found in
      the frequency of the types (with an exception on 'physical neglect') between
      males and females (P > 0.05). The highest frequency (42.9%) of CN was seen in the
      single-parent families and the lowest in large family with three generations
      (25.5%). (2) According to monofactorial chi(2) test, the possible risk factors of
      CN would include: educational background, occupation and decrease of income of
      the parents during last year, etc. (3) Binary Logistic regression analysis showed
      that the influential factors to the occurrence of CN would include: father's
      educational background, sex of the child and mother's occupation, etc. (4)
      Multiple linear regression showed that the influential factors to the degree of
      CN were: family structure, number of supporting family members, relationship
      between parents and children, etc. CONCLUSION: The degree and frequency of CN
      among children aged 3 to 6 in the urban areas of China were high but similar
      among the four age groups. Male children had a higher frequency of neglect than
      females, but with similar degree. Children in single-parent families had the
      highest frequency. The major influential factors of CN would include: educational
      background, occupation, family structure, family income of the parents which were
      similar to the results reported from foreign literature.

PMID- 15941533
TI  - [Analysis on the relationship between malaria epidemics and NOAA-AVHRR NDVI in
      Hainan province].
AB  - OBJECTIVE: To explore the relationship between malaria epidemics and NOAA-AVHRR
      NDVI. METHODS: Data on malaria were collected in all 19 counties in Hainan
      province from Feb, 1995 to Jan, 1996. Values regarding normalized difference
      vegetation index (NDVI)-related indicators including mean and maximum values of
      NDVI, the area proportion of NDVI values of 145- and 145+, months with NDVI
      values of 135+, 140+, 145+, 150+ of these counties in this period were all
      extracted from NOAA-AVHRR images, using ERDAS8.5 software. The coefficients of
      correlation of malaria incidences and these NDVI-related indicator values were
      then calculated with SPSS 11.0. RESULTS: The incidence of malaria showed positive
      correlations to mean and maximum values of NDVI, the area proportion of NDVI
      values of 145+ and months with NDVI values of 135+, 140+, 145+, 150+
      respectively, but having negative correlation to the area of NDVI values of 145-.
      The malaria epidemic regions were in accordance with those regions that the NDVI
      values of 145+ were continuing for 9 months or more. CONCLUSION: Malaria
      prevalence was associated with NOAA-AVHRR NDVI value which could be considered to
      be use for malaria surveillance in Hainan province.

PMID- 15941535
TI  - [Study on prevalence and correlation factors of bronchial asthma in Zaozhuang
      area, Shandong province].
AB  - OBJECTIVE: To study the prevalence of asthma and its correlated factors in
      Zaozhuang area in 2003, to provide a basic consideration for prevention/treatment
      and control policy. METHODS: 6 points were selected by stratified-clusterd-random
      sampling with a total of 16,725 persons expected, but only 10,610 subjects
      investigated. RESULTS: In this survey, 128 asthma cases were identified with a
      overall prevalence of 1.21%. The prevalence for children was 2.02%, and for adult
      was 0.90% with the former significantly higher then the latter (chi(2) = 21.39, P
      < 0.01). Rates for male and female were 1.08%, 1.32% with a ratio of 1:1.22. For
      77.97% of children with asthma. The initiative age of asthma was before 7 years
      old among children while among 36.23% of the adults, it was before 15 years of
      age. Correlation analysis showed that upper respiratory tract infection (OR =
      17.81, 95% CI: 12.25-25.89), cold air exposure (OR = 3.43, 95% CI: 2.41-4.90),
      stimulation through cooking and by harmful gases (OR = 2.56, 95% CI: 1.80-3.63),
      allergic materials (OR = 2.74, 95% CI: 1.80-4.17) were main inducing factors.
      65.63% of the asthma cases having had history of allergic disease while 25.78%
      having had family history with the OR of allergic history and family history as
      21.69 vs. 73.96. CONCLUSION: The epidemic status of bronchial asthma was serious,
      with an assumption that asthma cases might have reached the number of 43 thousand
      in Zaozhuang area.

PMID- 15941534
TI  - [Effect of multiple micronutrients supplementation on anti-oxidative activity and
      oxidized DNA damage of lymphocytes in children].
AB  - OBJECTIVE: To examine the effect of multiple micronutrients supplementation on
      anti-oxidative activity and decreasing oxidized DNA damage of lymphocytes in
      Chinese children. METHODS: 82 healthy children in a rural areas, aged 9-11 years,
      were selected and randomized allocated into group receiving supplements and
      control group with each of them 41. 24-hour dietary recall was used to collect
      data on daily nutrient intakes of the research subjects. The subjects in the
      supplement group were given vitamin A (VA) 600 microg, beta-carotene (beta-C) 1.0
      mg, vitamin E (VE) 100 mg, vitamin C (VC) 300 mg and Na2SeO3(Se) 200 microg in a
      tablet on daily base while those in the control group took a same-sized color
      placebo tablet. The trial lasted 8 weeks. 5 ml blood samples from each subject
      were taken during 7 to 9 o'clock in the morning. DNA damage of lymphocytes and
      levels of plasma VA, VE, VC, beta-C, Se, malondialdehyde (MDA), activities of
      superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were then analyzed
      twice before and after the 8-week of trial. RESULTS: The low intakes of VA, VC
      and Se only accounted for 50.6%, 65.6% and 67.3% of their recommended nutrient
      intake (RNI) respectively. After the trial, levels of plasma beta-C, VA, VE, VC
      and Se in the supplemented group increased by 13.4%, 32.8%, 11.5%, 46.9% and
      24.6% respectively, compared with the control group, indicating that nutritional
      status regarding antioxidant nutrients had largely been improved. GSH-Px activity
      had a significant increase in the supplement group than before the supplement and
      in the control group (P < 0.01). GSH-Px before the trial (the 100.4 U/ml) also
      showed significant increase after the trial (161.7 U/ml) (P < 0.01). However, the
      values of SOD and MDA significantly decreased after the trial. Analysis of DNA
      damage indicated that there was no significant difference in the intrinsic damage
      of DNA (P > 0.05). Significant decreases of oxidized DNA damage induced by 5
      micromol/L, 10 micromol/L and 25 micromol/L H2O2 were found more in peripheral
      lymphocytes of the supplemented group, than in pre-supplement and the control
      group after the trial (P < 0.01). CONCLUSION: Supplementation of multiple
      micronutrients could effectively increase the levels of beta-C, VA, VE, VC and Se
      in plasma, and GSH-Px activity. In the meantime, MDA and oxidized DNA damage
      induced by a low level H2O2 decreased significantly after the trial. The reason
      accounted for the decrease of SOD activity after the trial needs to be further
      studied.

PMID- 15941537
TI  - [Development and application of triple antibodies-based sandwich ELISA for
      detecting nucleocapsid protein of SARS-associated coronavirus].
AB  - OBJECTIVE: To prepare and characterize monoclonal antibodies (mAb) and polyclonal
      antibodies against nucleocapsid (N) protein of severe acute respiratory syndrome
      (SARS)-associated coronavirus (SARS-CoV) and to establish antibodies-based
      sandwich ELISA for detecting N protein of SARS-CoV, which might apply to early
      diagnosis of patients with SARS-CoV infection. METHODS: BALB/c mice were
      immunized with purified recombinant N protein of SARS-CoV for producing mAbs, and
      New Zealand white rabbits were immunized for producing polyclonal antibodies. The
      identification of antibodies was performed using indirect enzyme-linked
      immunosorbent assay (ELISA), indirect fluorescent-antibody assay (IFA), and
      Western immunoblotting. Capturing and detecting antibodies were selected by
      pairing the mAbs and polyclonal antibodies one by one and an antibodies-based
      sandwich antigen capture ELISA was used for detecting N antigen of SARS-CoV.
      RESULTS: Nine mAbs and hyperimmune rabbit polyclonal antibodies, specifically
      against SARS-CoV nucleocapsid protein were obtained. Using paired ELISA assay,
      three mAbs N1E8, N8E1 and N10E4 were selected as capturing antibody and rabbit
      polyclonal antibodies as detecting antibody then triple antibodies-based sandwich
      ELISA was established following horseradish peroxidase (HRP)-conjugated goat anti
      rabbit immunoglobulin G. The recombinant N protein was used as a standard to
      establish a detection sensitivity of approximated 50 pg/ml with this assay. When
      tested with 420 serum specimens from serologically confirmed SARS patients, the
      positive rates of serum N protein were 90.1%, 23% and 0%, in which sera collected
      from 1 to 10 days, 11 to 20 days and beyond 21 days respectively after the onset
      of symptoms. The specificity of the assay was 99.86% in 715 control serum
      specimens. There was no cross-reaction with other respiratory viruses and
      coronaviruses. CONCLUSION: Specific and high affinity mAbs and rabbit polyclonal
      antibodies were obtained. By paired and optimized sandwich ELISA, a sensitive and
      specific antigen capture ELISA was established for detecting N antigen of SARS
      CoV, which might apply to early diagnosis, source tracing and epidemiological
      studies of SARS.

PMID- 15941539
TI  - [Sequence analysis of Echovirus type 30 isolated from an aseptic meningitis
      outbreak in northern Jiangsu province in 2003].
AB  - OBJECTIVE: To determine the partial sequence of virus strains causing an aseptic
      meningitis outbreak in northern part of Jiangsu province in 2003 and to compare
      them with the same serotype strains isolated in other countries to better
      understand its genetic characteristics and hereditary trend of development.
      METHODS: Virus RNA was amplified using two sets of specific enteroviral 3' half
      of VP1 primers 012/011 and 040/011. Polymerase chain reaction (PCR) products were
      purified and sequenced. BLAST program was then used to perform on nucleotide and
      amino acid pairwise-alignment with all available sequences in NCBI database.
      Phylogenetic trees were drawed to compare with other enteroviral sequences using
      PHYLIP software. RESULTS: Under BLAST program, three sequences we submitted to
      GenBank were identically inferred as echovirus type 30, which had been identified
      by neutralization test in previous study. Phylogenetic analysis demonstrated that
      strains isolated from this outbreak were aggregated into a cluster, and the
      closest relationships with them were those isolated in 1999 and 2000. This
      phenomenon indicated that Echo30 from this outbreak was different from other
      strains in different epidemic area. CONCLUSION: 3' half of VP1 sequence could be
      used to quickly identify the serotype of isolated enterovirus. Strains isolated
      from this outbreak had the similar hereditary developing trend comparing with
      Echo30 strains isolated from other countries.

PMID- 15941540
TI  - [Immunogenetic analysis of human leukocyte antigen DRB1, DQB1 locus among Han
      ethnic children with Helicobacter pylori infection in Kunming].
AB  - OBJECTIVE: To explore the immunogenetic features of human leukocyte antigen DRB1,
      DQB1 locus and children with Helicobacter pylori (H. pylori) infection in Han
      ethnic population in Kunming and its association with digestive diseases and H.
      pylori to better understand the immunogenetic features of the H. pylori
      infection. METHODS: Polymerase chain reaction-sequence specific primer (PCR-SSP)
      method was used to study the HLA-DRB1, DQB1 allelic frequency distribution on 35
      children with H. pylori infection and 37 healthy controls in Han ethnic
      population in Kunming. RESULTS: Allelic frequencies of HLA-DRB1 * 0901, DQB1 *
      03032 in the H. pylori infection group were lower than those of the healthy
      control group (7.14% vs. 31.08%, chi(2) = 13.16, Pc < 0.012; 5.71% vs. 25.68%,
      chi(2) = 10.68, Pc = 0.007) but the rest alleles' frequencies did not show
      significant differences. CONCLUSION: These result suggested that HLA-DRB1 * 0901,
      DQB1 * 03032 might protect the H. pylori infection in Han ethnic population in
      Kunming.

PMID- 15941541
TI  - [A Meta-analysis in multi-center random controlled clinical trials].
AB  - OBJECTIVE: To study the center effect discrepancy in the multi-center clinical
      trials. METHODS: Two groups of data collected from the multi-center clinical
      trials were used. Data were processed by covariance analysis and Meta-analysis.
      RESULTS: In the covariance analysis, the discrepancy of the center effect values
      indicated statistical significance. Through Meta-analysis on fixed effect model,
      the discrepancy in one heterogeneity test showed no statistical significance (P >
      0.05) while the inter-group discrepancy of the merged effect values drawn from
      analysis based on fixed effect model having statistical significance (P < 0.05).
      In the random effect model, the discrepancy in one heterogeneity test showed
      statistical significance (P < 0.05) while the inter-group discrepancy of the
      merged effect values drawn from analysis based on random effect model having no
      statistical significance (P > 0.05). CONCLUSIONS: Studies on multi-center random
      controlled clinical trials, when statistical significance was found in the
      interaction discrepancy between the inter-center and the center-group relation,
      the merged effect values should be compared and analyzed by an appropriate
      statistic model based on the heterogeneous test results from the Meta-analysis.
      However, if the result from covariance analysis and the one from Meta-analysis
      did not agree to each other, the results drawn from the Meta-analysis were
      reliable.

PMID- 15941542
TI  - [The use of Meta-analysis in the evaluation on diagnostic tests].
AB  - OBJECTIVE: To introduce Meta-analysis in evaluating diagnostic tests. METHOD:
      Adjusted SROC method was used in assessing 7 diagnostic tests on fatty liver.
      RESULTS: The pooled sensitivity and specificity of type B ultrasonography were
      0.89 [95% confidence interval (CI): 0.87-0.92] and 0.94 (95% CI: 0.92-0.96)
      respectively while the Q value was 0.90 by adjusted SROC method. The results
      indicated that the diagnostic value of type B ultrasonography were high, thus
      could be regarded as an effective method for fatty liver diagnosis. CONCLUSION:
      Meta-analysis on evaluating diagnostic tests could be used to assess the
      diagnostic test to increase the power of conclusion, and to improves its
      reliability.

PMID- 15941543
TI  - [The application of structural equation model approach in epidemiological
      research].
AB  - OBJECTIVE: To discuss application of structural equation model (SEM) approach in
      epidemiological research. METHODS: A brief overview on major components of SEM,
      statistical assumptions underlying the use of SEM, and current software available
      to users and how SEM can be used were discussed through a practical
      epidemiological research project. RESULTS: Advantages of SEM comparing with
      conventional epidemiological approach were shown. SEM, having the nature of
      comprehensive thinking and analytic approach, not only exploring the association
      between factors and diseases but also among factors. It also served a
      confirmatory, rather than exploratory approach on data modeling, as well as
      having the capability of correcting estimates by separating measurement error
      from the equations, to provide modeling the latent variables. CONCLUSION: SEM
      approach could be used in epidemiological research as having some advantages
      comparing with conventional epidemiological approaches.

PMID- 15941549
TI  - [Use of antipsychotic drugs. A multicentric study of inpatients with acute
      psychotic disorders].
AB  - With the objective of determining the pattern and decision making process in
      using antipsychotic drugs in patients admitted to hospital for acute psychotic
      disorder we have made a retrospective analysis in 244 in-patients in 7 hospitals
      for mental disorders. We have selected two groups, IM and PO, that in the first
      three days of internment have received either intravenous antipsychotic
      medication or oral medication; the demographical, clinical and therapeutical
      differences have been considered (with a review of the cases at 6 and 12 months
      after discharge from hospital). Homogeneity was considered regarding age, race,
      gender, age at the onset of the disease and diagnosis; in the IM group there were
      a larger number of compulsive admissions. The most prevalent psychotic disorders
      in both groups were schizophrenia and bipolar disorder; with no association being
      made between the initial diagnosis and drug administration. The hospitalization
      period was the same for both groups, although in the patients in the IM group the
      need for special precautions was more frequent. Medication with anxiolytics was
      higher in the PO group on day 1 and 2 of the hospitalization and the same for the
      two groups on day 3 and on discharge. The number of new admissions, as well as
      the percentage of patients taking antipsychotic, anxiolytic and anticholinergic
      medication was similar in both groups after a period of 6 and 12 months follow
      up. In this study, agitation and aggressive/destructive behaviours in the initial
      phase of hospitalization in the IM group (including the first contact, most of
      the times on admission at the ER) were statistically significant factors for the
      use of intramuscular administration of antipsychotic drugs.

PMID- 15941550
TI  - [Internal medicine consultation].
AB  - The Internal Medicine consultation plays an important part in the activity of the
      Medicine Department. This activity is seldom quantified and is usually
      underestimated. In order to assess the work load represented by this service, the
      authors designed a prospective study to quantify and analyse the characteristics
      of the 556 consecutive consultations performed during 12 months. Over half the
      requests for observation were received after 4 p.m. and 18% were requested
      urgently; 96,8% were answered on the same day. Of the consultations, 33% came
      from the Orthopaedics and Trauma Department, 18% from the General Surgery
      Department and 17% from the Surgical Intermediate Care Unit. Cardio-vascular,
      infectious and neurological pathology accounted for most of the calls. During the
      regular working hours, there was'nt a direct contact with the patient's physician
      in 54% of the consultations. This activity represents an important additional
      work load to the Internist, with increasing relevance in the improvement of
      medical care. Our results highlight the need to establish a general medicine
      consultation service in every Internal Medicine Department and to include this
      activity in future educational programs.

PMID- 15941551
TI  - [Prognostic value of c-erb-2 immunohistochemistry expression in patients with
      primary breast cancer and adjuvant treatment with tamoxifen].
AB  - INTRODUCTION: The c-erb2 proto-oncogene is a member of the epidermal growth
      factor receptor family and has been associated with a more aggressive breast
      tumour biology and resistance to some types of treatments. AIMS: To evaluate the
      prognostic value of c-erb-2 receptor, from primary breast cancer on tamoxifen
      therapy. METHODS: We examined 66 paraffin-embedded sections from primary breast
      cancers. Patients were treated with surgery plus adjuvant treatment with
      tamoxifen; 58% had also received chemotherapy and/or radiotherapy. Membrane
      staining for c-erb-2 was evaluated by immunohistochemistry and overall survival
      and relapse-free survival were compared between positives and negatives for c-erb
      2. RESULTS: 43,9% of tumours over expressed c-erb-2 receptor, but this was not
      associated with a worse prognosis on overall survival either on relapse free
      survival, with a p value of 0,15 and 0,2 respectively. CONCLUSIONS: There is not
      any advantage to determine c-erb-2 as a prognostic factor on overall survival
      either on relapse free-survival. Attending the homogenous characteristics between
      both groups with any statistical differences according age.

PMID- 15941552
TI  - [Cervical smear, viral load and t cell counting in seropositive HIV women].
AB  - The aim of this study was to compare the T cell counting and viral load in
      seropositive women for HIV with normal cervical smear and intraepithelial
      lesions. 87 women were studied, 26 with normal smear, 46 with low grade
      intraepithelial lesions and 15 with high grade intraepithelial lesions. Women
      with normal smears showed the lowest viral load and high grade lesions the
      highest. There were no differences between cervical smear result and T cell
      counting.

PMID- 15941553
TI  - [Seroepidemiological survey of the human immunodeficiency Virus, type 2].
AB  - OBJECTIVES: To perform a seroepidemiological study and identify associated
      factors in a population infected by Human Immunodeficiency Virus, type 2 (HIV-2).
      A total of 2202 individuals were tested to determine the seroprevalence of this
      virus. METHODS: A nine-years retrospective study was performed in 211 HIV-2
      seropositives screened by ELISA and confirmed by Western Blot analysis. Eighty
      two individuals were analised by synthetic peptides and 15 had an antibody
      pattern of double reactivity to HIV-1 and HIV-2. RESULTS: The mean age of the HIV
      2 - infected individuals was 37.44+/-14.83 years (men 38,34+/-17,18 years; women
      36,77+/-12,89 years). There were 23.7% infection cases (95% CI, 18.1-30.0) in the
      age group 40-49 years. The infection was higher in females 57.8% (95% CI, 50.8
      64.6) than in males 42.2% (95% CI, 35.4-49.2). HIV-2 infection in Blacks was 61.6
      % (95% CI, 54.7-68.2). In respects to their geographical origin, the Portuguese
      represented 51.7% (95% CI, 44.7-58.6) followed by Guinean (Bissau) with 26.5%
      (95% CI, 20.7-33.0). The main mode of transmission of HIV-2 infection appears to
      be heterosexual transmission with 59.3% (95% CI, 47.8-70.1). Most of the
      evaluated individuals 54.3% (95% CI, 46.6-61.9) were classified as CDC stage II.
      HIV-2 seroprevalence was 1%. CONCLUSIONS: In considering the comparative data on
      the two periods of 4.5 years each, an increase of the infection in Caucasians
      from 32.4% to 43.4% was seen as well as a reduction in Blacks from 67.6% to
      55.7%. An increase in asymptomatic persons and a reduction in the CDC stage IV/C1
      was also observed. This study emphasis the need to continue efforts to decrease
      transmission of HIV-2 that should be directed toward epidemic and endemic regions
      and education about the risks of sexual transmission and how to decrease
      transmission by this route.

PMID- 15941554
TI  - [Reported cases of malaria in the north of Portugal (1993-2002)].
AB  - The aim of this study is to provide epidemiological evidence useful to Portuguese
      health services dealing with prevention and treatment of malaria. Two sources of
      data were used: the computer database of statutory notifiable diseases and the
      reports of cases studied by local health authorities. The 140 cases of malaria
      reported between 1993 and 2002 in the North of Portugal are described. For the 26
      available reports of cases occurred between 2000 and 2002 additional variables
      are described. The incidence rates of malaria, estimated for the period 1993
      2002, respectively for Portugal and its Northern Region, were 0,74 and 0,45 per
      100,000 persons-year. Incidence was stable across the studied period. Most cases
      were males aged 15 to 64. Most cases with laboratory confirmation were due to
      Plasmodium falciparum. Clinical picture, travelling details and preventive
      measures, namely chemoprophylaxis, were also described. All cases were imported,
      mostly from Portuguese speaking African countries. The usefulness of reporting
      cases of malaria and conducting the respective study was discussed.

PMID- 15941555
TI  - [Echovirus type 13 meningitis: admissions to a paediatric ward at a Lisbon
      hospital].
AB  - Infections by echovirus 13 are rare. In our country, it had not been previously
      reported any infection of this sort until 2000, when eleven echovirus 13
      meningitis were observed in the Department of Pediatrics of the Hospital Fernando
      Fonseca. In England and Spain outbreaks of echovirus 13 meningitis during 2000
      was also reported. Based on these facts the authors make an epidemiological
      analyses of their series.

PMID- 15941556
TI  - [Hepatitis B virus vaccination rate with immunization].
AB  - The hepatitis B virus is an important cause of morbidity and mortality in humans,
      thus making it a serious public health issue. The purpose of this study was to
      determine the hepatitis B virus vaccination rate with immunization, the risk of
      this population group becoming infected before vaccination and the prevalence of
      hepatitis B virus infection. The study involved randomly analyzing the serum of
      311 adolescents of both sexes aged 14 from a total population of 536 adolescents
      attending schools in Braga, Portugal. A questionnaire was administered to the
      adolescents and asked them if they had received the Hepatitis B vaccine, how many
      doses they received, if they had a history of acute hepatitis, drug abuse,
      whether or not they had had sexual intercourse and if so, if they had used
      protection. The determination of the hepatitis B surface antigen (HbsAg), the
      antibody to HbsAg and the antibody to hepatitis B core antigen was carried out
      using the chemoluminiscence method. The vaccination rate with immunization was
      85.8 %, [95% CI 81.9-89.7%]. The prevalence of hepatitis B virus infection was
      0.6%, [95% CI 0-1.5%]. CONCLUSIONS: The prevalence of hepatitis B virus infection
      was low in this adolescent population of Braga. The vaccination rate with
      immunization is satisfactory, but does not reach 100%, which means that the risk
      of transmission is still present in this age group.

PMID- 15941557
TI  - [The scientific activity and research in a central hospital: a retrospective
      analysis of ten years].
AB  - INTRODUCTION: The scientific activity performed by doctors, whilst working in
      central hospitals, should be the major setting for clinical research. The purpose
      of this retrospective study was to measure the scientific activity and clinical
      research carried out by the medical staff at the central Hospital Dona Estefania.
      METHODS: Between 1993 and 2002 (ten years) the abstracts included in the Hospital
      Dona Estefania's Scientific Year Book were analyzed. The type of studies, the
      number of communications and publications, and the scientific production (based
      on the ratio of number of studies per doctor in each specialty and subspecialty)
      were determined. RESULTS: During the ten years analyzed, 1821 studies were
      included and 49.7% of them were considered to be clinical research; the mean
      annual scientific production of the Hospital was 182 studies, 165 communications
      and 24.5 publications. During the year of 2002, 312 doctors in 24 specialties and
      subspecialties were considered, with a mean ratio per doctor of 0.73 studies,
      including 0.29 research studies. CONCLUSIONS: The Scientific Year Book was an
      extremely useful tool to directly measure the scientific activity and research of
      doctors working at the Hospital, including published and unpublished papers. As
      yet, there is no similar national study available to compare the obtained
      results. Nonetheless, the analyzed scientific activity, particularly the clinical
      research, appears to be insufficient considering that the analyzed scientific
      production belongs to a central hospital. The excessive clinical work and the
      negligible value for research considered in the Portuguese national regulations
      for contracting doctors for the permanent staff of central hospitals may have
      contributed towards the poor motivation of doctors in research found in this
      study.

PMID- 15941558
TI  - [Acute pancreatitis: update and approach protocol proposal].
AB  - Acute pancreatitis, a broad spectrum pathology, has a variable incidence, closely
      related to the geographic differences in its most frequent etiologies. Its
      pathogenesis remains to be cleared, with several proposed mechanisms.
      Pancreatitis' diagnosis, severity evaluation and the use of imagiologic and
      endoscopic auxiliary exams must be based in scientifically settled criteria.
      Treatment depends, mostly, on the episode's severity, but is mainly supportive.
      Pancreatitis' complications are responsible for the lethal cases and their
      classification as early, intermediate and late has practical utility. Based on a
      literature review of the pathology, including reference books and computer data
      bases, a systematized approach algorithm is proposed.

PMID- 15941559
TI  - [Synovial lipoma arborescens].
AB  - Lipoma arborescens is a rare intraarticular lesion of unknown etiology. The
      disorder usually presents as painless swelling and recurrent joint effusion. It
      is typically located in the knee (especially the suprapatellar bursa), though it
      has also been described in other joints. Laboratory test results are normal, as
      well as aspirated synovial fluid. Synovectomy is curative in most cases. The
      authors report a review of the literature, highlighting the importance of
      magnetic resonance imaging in the diagnosis of this pathology. Although it is a
      rare lesion, synovial lipoma arborescens should be included in the differential
      diagnosis of patients with a chronic swollen joint or recurrent joint effusions.

PMID- 15941560
TI  - [Thyroid associated ophthalmopathy].
AB  - Thyroid associated ophthalmopathy is an uncommon disease, characterized by a
      diffuse inflammation of the orbit in a bilateral and asymmetric pattern, causing
      proptosis and swelling of the eyelids and conjuntiva. In 90% of the patients it
      is associated with Graves' disease, however it may occur with hipothyroidism or
      even without thyroid disease. During its course spontaneous remission or
      exacerbations are common, evolving independently from the thyroid disease, most
      often without serious complications for the patient, being blindness the worse of
      them, in 1% of the cases. The cause is still misunderstood but it is thought to
      be the result of an immune system disorder with the production of auto-antibodies
      directed against retro-bulbar fibroblasts and thyroid. Therapeutics is still a
      controversial matter. The balance between benefits and medication adverse effects
      is still to be made.

PMID- 15941561
TI  - [Congenital or neonatal cytomegalovirus infection?].
AB  - Congenital Cytomegalovirus (CMV) infection occurs in about 1% of the newborns,
      but it is clinically unapparent in around 90% of the cases during the newborn
      period. This congenital infection may be the cause of neurological sequelae of
      variable severity, namely neuro-sensorial hearing loss. In most cases of hearing
      loss secondary to congenital CMV infection, the newborn was asymptomatic. The
      diagnosis of congenital CMV infection is made traditionally by culturing the
      virus from urine during the first three weeks of life. In the present case, the
      authors describe the situation of a two months old black female infant, admitted
      for irritability, vomiting and generalized convulsions. During investigation, the
      authors found lab results in favor of recent CMV infection. The imaging studies
      performed (cerebral ultrasound scan, computerized tomography and magnetic
      resonance imaging) were normal. As the infant was older than three weeks, it was
      not possible to make the diagnosis of congenital CMV infection by a positive
      urine sample. The diagnosis was made by a positive Polymerase Chain Reaction made
      on the Guthrie card, collected on the fifth day of life and archived in the
      national laboratory that centralizes the early diagnosis of phenylketonuria and
      hypothyroidism. The authors review the epidemiology, diagnosis, prognosis and
      prevention of the congenital CMV infection, giving a perspective of the magnitude
      of this disease, its sequelae and the new diagnostic methods available, even when
      the infection is clinically unapparent on the newborn period.

PMID- 15941562
TI  - Effects of training intensity on observers' ratings of anxiety, social skills,
      and alcohol-specific coping skills.
AB  - Few studies have addressed the amount of training needed to obtain reliable
      ratings in behavioral observation data. The current study examined the effects of
      differing intensities of frame-of-reference (FOR) rater training on observers'
      ratings of anxiety, social skills, and alcohol-specific coping skills in
      community volunteers with and without social anxiety and alcohol use disorders.
      Interrater reliability was assessed by comparing three training conditions (no
      training, moderate FOR, and intensive FOR) on discrepancies between raters'scores
      and the strength of association between raters'scoring patterns. The
      discrepancies between raters' scores were significantly larger in the control
      condition than in the intensive and moderate training conditions. Generally,
      small and nonsignificant differences were found between intensive and moderate
      training's discrepancy scores. Strength of association results showed
      significantly lower correlations in the control group compared to the intensive
      group. However, these correlational results showed less consistent differences
      between the moderate and other training conditions; differences when found were
      in the expected directions. Study findings suggest that differing training
      intensities can affect rating scores and that interrater reliability may be
      meaningfully assessed through multiple methods.

PMID- 15941564
TI  - Hydration of phospholipid bilayers in the presence and absence of cholesterol.
AB  - The number of water molecules bound (unfreezable) by a molecule of dipalmitoyl
      phosphatidylserine (DPPS) or by a molecule of dipalmitoyl phosphatidylcholine
      (DPPC) alone or in mixtures with cholesterol was determined by differential
      scanning calorimetry (DSC). When the phospholipids are in the gel state and in
      the absence of cholesterol, molecule of DPPS binds about 3.5 molecules of water
      and molecule of DPPC binds about 6 molecules of water. Number of water molecules
      bound increases when cholesterol crystallites are formed in the bilayer. For DPPS
      cholesterol mixture at X(chol) -0.5, as well as for DPPC-cholesterol mixture at
      X(chol) -0.5 about 7 water molecules are bound.

PMID- 15941563
TI  - Emodin induces apoptosis in human lung adenocarcinoma cells through a reactive
      oxygen species-dependent mitochondrial signaling pathway.
AB  - Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has
      been reported to exhibit anti-cancer effect on several human cancers such as
      liver cancers and lung cancers. However, the molecular mechanisms of emodin
      mediated tumor regression have not been fully defined. In this study, we show
      that treatment with 50 microM emodin resulted in a pronounced release of
      cytochrome c, activation of caspase-2, -3, and -9, and apoptosis in human lung
      adenocarcinoma A549 cells. These events were accompanied by the inactivation of
      ERK and AKT, generation of reactive oxygen species (ROS), disruption of
      mitochondrial membrane potential ((Delta)psi(m)), decrease of mitochondrial Bcl
      2, and increase of mitochondrial Bax content. Ectopic expression of Bcl-2, or
      treatment with aurintricarboxylic acid, furosemide or caspase inhibitors markedly
      blocked emodin-induced apoptosis. Conversely, pharmacologic ERK and AKT
      inhibition promoted emodin-induced apoptosis. Furthermore, the free radical
      scavenger ascorbic acid and N-acetylcysteine attenuated emodin-mediated ROS
      production, ERK and AKT inactivation, mitochondrial dysfunction, Bcl-2/Bax
      modulation, and apoptosis. Take together, these findings suggest that in A549
      cells, emodin-mediated oxidative injury acts as an early and upstream change in
      the cell death cascade to antagonize cytoprotective ERK and AKT signaling,
      triggers mitochondrial dysfunction, Bcl-2 and Bax modulation, mitochondrial
      cytochrome c release, caspase activation, and consequent leading to apoptosis.

PMID- 15941565
TI  - Proteomics: the next revolution in laboratory medicine?
AB  - BACKGROUND: The identification of specific genetic alterations and protein
      profiles associated with disease offers a unique opportunity to develop
      proteomics-based assays for early diagnosis. By identifying proteins in
      serum/plasma, a minimally invasive tool is used to assess the presence of disease
      and to monitor response to treatment and/or disease progression. The potential
      clinical applications of this tool are broad-based, including the diagnosis not
      only of cancer but also cardiovascular and neuromuscular diseases, organ
      transplantation associated conditions, and infertility. METHODS: A number of
      competing chromatographic techniques have been proposed for overcoming the
      complexity and labor-intensive manipulations associated with the traditional
      technique for proteomic analysis, which is based on two-dimensional gel
      electrophoretic techniques. However, mass spectrometry has now assumed a central
      role in most proteomic workflows, and several combinations of ionization sources,
      analyzers and fragmentations devices have been described and developed. RESULTS:
      Thanks to proteomic applications in the diagnosis of cancer, several research
      groups have identified proteomic patterns associated with ovarian, prostatic,
      colorectal and other cancers. While the sensitivity and specificity of these
      patterns are highly satisfactory, there are still some open questions concerning
      the standardization, reproducibility, and inter-laboratory agreement of these
      data. CONCLUSIONS: Proteomics, and, in particular, serum mass spectroscopic
      proteomic pattern diagnostics, is a rapid expanding field of research. The plasma
      proteoma has an important position at the intersection between genes and
      diseases, and clinical laboratories must adapt to a new era of tests based on
      proteomics and genomics. In the future, mass spectrometry will become an
      essential tool in the clinical laboratory.

PMID- 15941566
TI  - Neointimal hyperplasia and vascular endothelial growth factor expression are
      increased in normoglycemic, insulin resistant, obese fatty rats.
AB  - OBJECTIVE: Insulin resistance is associated with a constellation of factors that
      enhance the artherosclerotic process. Vessel injury results in the formation of a
      markedly increased neointima in type 2 diabetes. Increased neointimal hyperplasia
      (NH) and vascular endothelial growth factor (VEGF) expression may lead to
      restenosis post angioplasty. We studied NH and VEGF expression in an obese,
      insulin resistant, but normoglycemic rat model, after carotid balloon injury.
      METHODS AND RESULTS: Diabetic rats (ZDF, n=10), normoglycemic, insulin-resistant
      rats (ZDF-normoglycemic, n=6) as well as Zucker fatty rats (FZ, n=6), and lean
      Zucker rats (LZ, n=6), all 13-16 weeks old, were subjected to right carotid
      injury by an angioplasty catheter introduced via the femoral artery. Three weeks
      later the rats were sacrificed and serum and carotids obtained. The intima-media
      ratio (I/M) was then calculated. ZDF-normoglycemic, FZ and ZDF-diabetic rats were
      all hyperinsulinemic and hypertriglyceridemic when compared to LZ rats. ZDF
      diabetic rats were hyperglycemic while FZ, ZDF-normoglycemic and LZ rats were
      normoglycemic. The I/M ratio for ZDF and FZ rats were significantly greater than
      for LZ rats. The VEGF expression was significantly greater in ZDF and FZ rats
      than LZ rats. CONCLUSIONS: In conclusion, insulin resistance increases neointimal
      hyperplasia and VEGF expression even with normoglycemia, after carotid
      angioplasty in rats.

PMID- 15941567
TI  - Lack of association between ADH3 polymorphism, alcohol intake, risk factors and
      carotid intima-media thickness.
AB  - OBJECTIVE: We assess the relationships between alcohol dehydrogenase 3 (ADH3)
      polymorphism, alcohol consumption and cardiovascular risk factor levels. METHODS:
      In a representative population sample from Southwestern France (614 men, 567
      women, age 49.7+/-8.5 years), alcohol intake was assessed by questionnaire.
      RESULTS: Alcohol consumption was significantly related with higher levels of
      total and HDL cholesterol, triglycerides, apolipoprotein A-I in men and with
      higher levels of HDL cholesterol in women. Also, an inverse relationship between
      alcohol consumption and intima-media thickness was found in men. Conversely, in
      both genders, no differences were found between ADH3 genotypes regarding all
      cardiovascular risk factors studied and carotid intima-media thickness. Also, in
      both genders, no significant ADH3xalcohol interaction was found for all
      variables, and further adjustment on age, body mass index, educational level,
      smoking status or after excluding subjects on hypolipidemic or antihypertensive
      drug treatment did not change the results. CONCLUSION: We found no interaction
      between the ADH3 polymorphism and alcohol intake on cardiovascular risk factor
      levels and atherosclerotic markers in Southwestern France.

PMID- 15941568
TI  - A functional role for inducible costimulator (ICOS) in atherosclerosis.
AB  - BACKGROUND: Lymphocytes appear to influence atherosclerosis by altering cytokine
      production. Whereas primary lymphocyte activation requires T cell receptor
      ligation, costimulatory signals also appear requisite for generation of a
      functional T cell response. Inducible costimulator (ICOS) is a newly discovered T
      cell molecule with a dual role in immune mediated disorders. Herein, we tested
      the importance of ICOS in atherosclerosis. METHODS AND RESULTS: Atherosclerotic
      plaques from ApoE-KO mice were studied immunohistochemically for the presence and
      localization of ICOS and its receptors and its expression in splenocytes. ApoE-KO
      mice were immunized with human ICOS/Fc-chimera or non-fused Fc and either
      provided a chow diet for 6 weeks, or a high fat diet for 8 weeks. ICOS and its
      ligand were abundantly expressed within plaques from ApoE-KO mice: Spleen cells
      from atherosclerotic mice exhibited lowered constitutive expression of ICOS yet
      priming with oxLDL enhanced ICOS expression dose-dependently. In mice induced to
      develop fatty streaks and to generate ICOS blocking antibodies, early
      atherosclerosis was increased by approximately 77% whereas upon inducing more
      advanced lesions, the increase in plaque area upon ICOS blockade group was
      approximately 36%. IFN-gamma secretion by oxLDL-primed splenocytes in ICOS
      immunized mice increased whereas IL-10 secretion diminished as compared to
      control animals. A similar trend in cytokine production was evident in the lesion
      by immunohistochemistry. CONCLUSION: ICOS appears as an influential costimulatory
      pathway in atherosclerosis that may play a protective rather that a
      proatherogenic role.

PMID- 15941569
TI  - Epstein Barr virus specific T-cells generated from unstable human atherosclerotic
      lesions: Implications for plaque inflammation.
AB  - OBJECTIVE: T-cell activation is an essential feature of atherosclerotic plaque
      inflammation, which eventually may lead to plaque rupture. In this study, we
      investigated if EBV, a common herpes virus, is capable of stimulating
      atherosclerotic plaque derived T-cells and thus could contribute to
      atherosclerotic plaque inflammation. METHODS: Plaque derived T-cell cultures were
      established from symptomatic carotid atherosclerotic plaques of 19 patients. B
      cells from the same patients were transformed with EBV to form lymphoblastoid
      cell lines (B-LCL) that served as antigen presenting cells. The proliferation of
      T-cells in the presence of autologous B-LCL was analyzed using 3H-thymidine
      incorporation. The presence of EBV in atherosclerotic material was analyzed by
      PCR. RESULTS: Of the 19 cell obtained T-cell cultures, 11 responded to EBV (58%,
      mean stimulation index: 10.1+/-3.1). PCR analysis showed that EBV DNA was present
      in 15 of the tissue samples (79%). All the specimens that contained EBV
      responding T-cells also contained EBV. EBV specific T-cells secreted granzymes,
      as indication of functional cytotoxic potential. CONCLUSIONS: EBV-specific
      cytotoxic T-cells and EBV DNA can be frequently observed in human atherosclerotic
      plaques. This suggests that a T-cell response against EBV could contribute to
      plaque inflammation, and thus to the onset of acute clinical symptoms.

PMID- 15941570
TI  - On the consequences of head size following impact to the human head.

PMID- 15941571
TI  - Dynamics of cuticular chemical profiles of Polistes dominulus workers in orphaned
      nests (Hymenoptera, Vespidae).
AB  - We analysed changes in cuticular hydrocarbon signatures of workers in orphaned
      colonies of the paper wasp Polistes dominulus. In natural conditions, workers and
      foundresses possess characteristic cuticular signatures, and foundresses are
      further distinguishable, both behaviourally and chemically, on the basis of their
      rank in a reproductive dominance hierarchy. In our study, several workers were
      found to develop their ovaries and produce cuticular signatures resembling those
      of dominant foundresses, while remaining workers possessed undeveloped ovaries
      and had cuticular blends characteristic of subordinate foundresses. Workers that
      did not develop their ovaries had changed epicuticular signatures, demonstrating
      that the mixture of hydrocarbons of worker individuals is strongly dependent on
      social role and environment. Our results suggest that the composition of
      epicuticular lipids is not determined at the pre-imaginal stage, and that
      physiological pathways leading to cuticular chemical changes are similar in
      foundresses and workers of P. dominulus.

PMID- 15941573
TI  - DNA base damage recognition and removal: new twists and grooves.
AB  - The discoveries of nucleotide excision repair and transcription-coupled repair
      led by Phil Hanawalt and a few colleagues sparked a dramatic evolution in our
      understanding of DNA and molecular biology by revealing the intriguing systems of
      DNA repair essential to life. In fact, modifications of the cut-and-patch
      principles identified by Phil Hanawalt and colleagues underlie many of the common
      themes for the recognition and removal of damaged DNA bases outlined in this
      review. The emergence of these common themes and a unified understanding have
      been greatly aided from the direct visualizations of repair proteins and their
      interactions with damaged DNA by structural biology. These visualizations of DNA
      repair structures have complemented the increasing wealth of biochemical and
      genetic information on DNA base damage responses by revealing general themes for
      the recognition of damaged bases, such as sequence-independent DNA recognition
      motifs, minor groove reading heads for initial damage recognition, and nucleotide
      flipping from the major groove into active-site pockets for high specificity of
      base damage recognition and removal. We know that repair intermediates are as
      harmful as the initial damage itself, and that these intermediates are protected
      from one repair step to the next by the enzymes involved, such that pathway
      specific handoffs must be efficiently coordinated. Here we focus on the
      structural biology of the repair enzymes and proteins that recognize specific
      base lesions and either initiate the base excision repair pathway or directly
      repair the damage in one step. This understanding of the molecular basis for DNA
      base integrity is fundamental to resolving key scientific, medical, and public
      health issues, including the evaluation of the risks from inherited repair
      protein mutations, environmental toxins, and medical procedures.

PMID- 15941572
TI  - Soluble adhesion molecules in Gilles de la Tourette's syndrome.
AB  - To investigate the immune-mediated response in TS, and its relationship with
      streptococcal infection, we measured serum levels of soluble intercellular
      adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E
      selectin in patients with TS, compared to healthy and diseased controls. Soluble
      VCAM-1 and sE-selectin were significantly elevated in children and adults with
      TS, and sVCAM-1 was higher among anti-basal ganglia antibodies (ABGA)-positive
      adults with TS. No correlation of adhesion molecule levels to clinical severity
      or anti-streptococcal antibodies was observed. Children with Sydenham's chorea
      and paediatric autoimmune neuropsychiatric disorders associated with
      streptococcal infections (PANDAS) showed an increased level of sICAM-1, but not
      sVCAM-1 and sE-selectin. These results provide initial evidence for a role of
      adhesion molecules and systemic inflammation in TS, and support the hypothesis of
      an ongoing immune-mediated process in this condition.

PMID- 15941574
TI  - Dietary preferences for feeds varying in threonine concentration by the piglet.
AB  - Two choice feeding trials were carried out to investigate if weaned piglets
      prefer feeds varying in threonine (Thr) content. In exp 1, two control groups
      were fed either a 0.57% Thr (negative control) or a 0.67% Thr (positive control)
      feed. Two other groups had the choice from 2 feeds containing 0.57% or 0.62% Thr
      (Thr-choice 1) and 0.57% or 0.67% Thr (Thr-choice 2). In exp 2 the two control
      groups were fed either a 0.50% Thr (negative control) or a 0.62% Thr (positive
      control) feed and the Thr-choice groups had the choice from 2 feeds containing
      0.50% or 0.56% (Thr-choice 1) and 0.50% or 0.62% Thr (Thr-choice 2),
      respectively. In exp 1, animals of the Thr-choice 1 showed a significant
      preference for the feed with the higher Thr content but in the Thr-choice 2, both
      feeds on offer were chosen at random. In exp 2 the preference for the higher Thr
      feeds in the Thr-choice groups 1 and 2 was on average 71% and 72%, respectively.
      In both experiments, the data of growth performance and plasma amino acid and
      urea pattern indicated a suboptimal Thr supply in the negative control and the
      Thr-choice 1 group. It is concluded that piglets are able to detect metabolic
      changes caused by a marginal Thr supply and that they change their feeding
      behaviour in order to overcome deficiency.

PMID- 15941575
TI  - Metal ion adsorption by Phomopsis sp. biomaterial in laboratory experiments and
      real wastewater treatments.
AB  - An insoluble material of polysaccharidic nature has been obtained by thermal
      alkali treatment of the filamentous fungus Phomopsis sp. FT-IR spectrum of the
      resulting material as well as its nitrogen content suggest that chitosan and
      glucans are the main components of the biomaterial. Information on Lewis base
      sites has also been obtained and used as a guideline in the evaluation of the
      complexing ability against a number of metal ions in aqueous media at pH in the
      range 4--6. Results indicate that after 24h contact time, up to 870 micromol/g of
      lead, 390 micromol/g of copper, 230 micromol/g of cadmium, 150 micromol/g of zinc
      and 110 micromol/g of nickel ions are adsorbed into the material. After
      approximately 10 min, about 70% of the overall adsorption process has already
      been completed. Adsorbed metal ions can be recovered by washing with dilute acid.
      Experiments have been extended to a real wastewater effluent confirming the
      potential of this biomaterial as a depolluting agent.

PMID- 15941576
TI  - Dechlorination of tetrachloroethylene by palladized iron in the presence of humic
      acid.
AB  - The dechlorination of tetrachloroethylene (PCE) by palladized irons in the
      presence of humic acid was investigated to understand the feasibility of using
      Pd/Fe for the in situ remediation of contaminated groundwater. Untreated
      zerovalent iron (ZVI) was amended with Pd(II) ions to form palladized irons. X
      ray photoelectron spectroscopy showed that Pd(II) was completely reduced to
      metallic Pd on the surface of ZVI. PCE was catalytically dechlorinated via beta
      elimination to ethane and ethylene by palladized irons. The carbon mass balances
      were in the range of 78--98%. The dechlorination followed the pseudo first-order
      rate equation and the normalized surface reaction rate constant (k(sa)) for PCE
      dechlorination was 33.47+/-7.21 L/m(2)h in the absence of humic acid. Humic acid
      competed the reactive sites on the palladized irons with PCE, and thus lowered
      the dechlorination efficiency and rate of PCE. After 24h of equilibrium between
      humic acid and palladized irons prior to the injection of PCE, however, the
      efficiency and rate of PCE dechlorination could increase with increasing
      concentrations of humic acid. Addition of quinones having low redox potentials
      including AQDS, lawsone and hydroquinone also enhanced the dechlorination
      efficiency of PCE after 24h, depicting that humic acids serve as the electron
      shuttles to effectively transfer electrons and to accelerate the dechlorination
      efficiency and rate of PCE.

PMID- 15941577
TI  - Calorie restriction and SIR2 genes--towards a mechanism.
AB  - Calorie restriction is the first and most compelling example of life extension in
      mammals. Much speculation about how CR works has focused on ideas of what causes
      aging. Since these causes themselves are much disputed, I have instead focused my
      thinking on lessons from simple model organisms, which have emerged from recent
      genetic studies. These findings can now be integrated with numerous, elegant
      studies on CR over the decades, which provide a treasure trove of information
      about physiological changes that are elicited by this regimen. In this paper, I
      present data showing that the SIR2 gene is a strong candidate to regulate CR in
      the simple model organisms, such as yeast and Drosophila. I then summarize what
      is known about the mammalian Sirt1 as it relates to physiological changes during
      CR, and discuss how this mechanism may impact on life span, as well as diseases
      of aging.

PMID- 15941578
TI  - The influence of a large city on some soil properties and metals content.
AB  - Urban soils differ from the rural ones by the fact that they are more strongly
      influenced by anthropogenic activities. This influence is often reflected by a
      high degree of contamination. To investigate the influence a large city can have
      on its soils and on the surrounding ones, samples within the city of Torino,
      Italy were compared with a set of surrounding soils developed from the same
      alluvial parent material. City-country trends were investigated by spatially
      managing the samples. Results show that the city plays a key role in
      concentrating some pollutants, such as Pb, Zn, and Cu within its borders. Lead is
      the element most enriched in the city, presenting a pollution index of 7.5
      calculated comparing the two sets of samples. Ni and Cr appear to have a strong
      natural contribution. The spatial distributions for Pb, Cu and Zn present an
      abrupt division between urban and rural samples. Unexpectedly, the transport of
      pollutants from the city to the surrounding areas seems to be limited as no city
      country trends with distance are identified. The pH and the sand fraction result
      also influenced by the city, showing high values. The investigation of possible
      city-country distance trends has shown to be effective in evaluating the impact a
      city can have on its soils and on the transport and deposition of contaminants on
      the surrounding ones.

PMID- 15941579
TI  - Embryotoxic activity and differential binding of plant-derived carbohydrate
      recognizing proteins towards the sea urchin embryo cells.
AB  - The embryotoxic activity and differential binding of plant-derived carbohydrate
      recognizing proteins on sea urchin (Lytechinus variegatus) embryo cells was
      investigated. IC50 doses for toxicity on larvae development varied from 0.6 up to
      96.3 microg ml(-1) and these effects were largely reversed by previously heating
      the proteins. Changes in the glycoconjungate status of the cell surface were
      assessed by time-course binding of the proteins during embryogenesis according to
      their carbohydrate-binding specificity. Glucose/mannose binding-proteins bound
      embryo cells at the same stage of development, at a similar stage to the N
      acetylglucosamine/N-acetylneuraminic acid binding-protein (WGA) and earlier than
      galactose specific ones. FITC-conjugates of these proteins confirmed the above
      results and revealed the presence of specific and differential receptors for
      them. Inhibition assays using inhibitory glycoproteins significantly diminished
      the labelled patterns of FITC-conjugates. In conclusion, the assayed proteins
      exhibited embryotoxicity and their binding requirements were useful for following
      changes in the pattern of cell surface glycoconjugates on embryo cells of sea
      urchin. This property could be useful in analyzing other cell types.

PMID- 15941580
TI  - Bioactive bone cements containing nano-sized titania particles for use as bone
      substitutes.
AB  - Three types of bioactive polymethylmethacrylate (PMMA)-based bone cement
      containing nano-sized titania (TiO2) particles were prepared, and their
      mechanical properties and osteoconductivity are evaluated. The three types of
      bioactive bone cement were T50c, ST50c, and ST60c, which contained 50 wt% TiO2,
      and 50 and 60 wt% silanized TiO2, respectively. Commercially available PMMA
      cement (PMMAc) was used as a control. The cements were inserted into rat tibiae
      and allowed to solidify in situ. After 6 and 12 weeks, tibiae were removed for
      evaluation of osteoconductivity using scanning electron microscopy (SEM), contact
      microradiography (CMR), and Giemsa surface staining. SEM revealed that ST60c and
      ST50c were directly apposed to bone while T50c and PMMAc were not. The
      osteoconduction of ST60c was significantly better than that of the other cements
      at each time interval, and the osteoconduction of T50c was no better than that of
      PMMAc. The compressive strength of ST60c was equivalent to that of PMMAc. These
      results show that ST60c is a promising material for use as a bone substitute.

PMID- 15941581
TI  - Engineered spatial patterns of FGF-2 immobilized on fibrin direct cell
      organization.
AB  - The purpose of this study was to initiate the exploration of cell behavioral
      responses to inkjet printed spatial patterns of hormones biologically immobilized
      on biomimetic substrates. This approach was investigated using the example of
      preosteoblastic cell response in vitro to fibroblast growth factor-2 (FGF-2)
      printed on fibrin films. Concentration modulated patterns of FGF-2, including
      continuous concentration gradients, were created by overprinting dilute FGF-2
      bioinks with a custom inkjet printer. The immobilized FGF-2 was biologically
      active and the printed patterns persisted up to 10 days under cell culture
      conditions. Cell numbers increased in register to printed patterns from an
      initial random uniform cell distribution across the patterned and non-patterned
      fibrin substrate. Patterned immobilized FGF-2, not cell attachment directed cell
      organization because the fibrin substrate was homogeneous. The capability to
      engineer arbitrary and persistent hormone patterns is relevant to basic studies
      across various fields including developmental biology and tissue regeneration.
      Furthermore, since this hormone inkjet printing methodology is extensible to
      create complex three-dimensional structures, this methodology has potential to
      create therapies for tissue engineering using spatial patterned delivery of
      exogenous hormones.

PMID- 15941582
TI  - Peripheral quantitative computed tomography in evaluation of bioactive glass
      incorporation with bone.
AB  - This laboratory study examined the feasibility of non-invasive, in vivo
      peripheral quantitative computed tomography (pQCT) method in evaluation of
      bioactive glass incorporation with bone. An intramedullary defect model of the
      rat tibia was applied. The defect was filled with bioactive glass microspheres
      (diameter of 250-315 microm) or was left to heal without filling (empty
      controls). The results of the pQCT analysis were compared with those of
      histomorphometry. In the control defects, there was a good correlation (r2 =
      0.776, p < 0.001) between the pQCT density of the intramedullary space and the
      amount of new bone measured by histomorphometry. In the defects filled with
      bioactive glass, the use of thresholding techniques of the applied pQCT system
      (Stratec XCT Research M) failed in separation of new bone formation and bioactive
      glass particles. However, detailed analysis of the pQCT attenuation profiles
      showed time-related changes which well matched with the histomorphometric results
      of new bone formation both in control and bioactive glass filled defects. The
      biphasic pQCT attenuation profiles of bioactive glass filled defects could be
      separated into two distinct peaks. In statistical analysis of various variables,
      the center (i.e. the value of attenuation) of the major attenuation peak was
      found to be the most significant indicator of the incorporation process. The
      center of the peak initially decreased (during the first 4 weeks of healing) and
      thereafter increased. These two phases probably reflect the primary resorption
      and reactivity of the bioactive glass microspheres in vivo followed by secondary
      new bone formation on their surfaces. Based on these results, pQCT-method seems
      to be suitable for in vivo follow-up of the bioactive glass incorporation
      processes. Although the imaging technique is not able to discriminate the
      individual microspheres from invading new bone unambiguously, the attenuation
      profiling seems to give adequate information about the state of the incorporation
      process. This information may help to establish non-invasive imaging techniques
      of synthetic bone substitutes for preclinical and clinical testing of their
      efficacy.

PMID- 15941583
TI  - Biomimetic deposition of apatite coating on surface-modified NiTi alloy.
AB  - TiO(2) coatings were prepared on NiTi alloy by heat treatment in air at 300, 400,
      600 and 800 degrees C. The heat-treated NiTi alloy was subsequently immersed in a
      simulated body fluid for the biomimetic deposition of the apatite layer onto the
      surface of TiO(2) coating. The apatite coatings as well as the surface oxide
      layer on NiTi alloy were characterized using scanning electron microscopy
      equipped with energy dispersive spectroscopy, X-ray diffraction, X-ray
      photoelectron spectroscopy and Raman spectroscopy. Results showed the samples
      heat-treated at 600 degrees C produced a layer of anatase and rutile TiO(2) on
      the surface of NiTi. No TiO(2) was detected on the surface of NiTi after heat
      treatment at 300 and 400 degrees C by X-ray diffraction, while rutile was formed
      on the surface of the 800 degrees C heat-treated sample. It was found that the
      600 degrees C heat-treated NiTi induced a layer consisted of microcrystalline
      carbonate containing hydroxyapatite on its surface most effectively, while 300
      and 400 degrees C heat-treated NiTi did not form apatite. This was due to the
      presence of anatase and/or rutile in the 600 and 800 degrees C heat-treated NiTi
      which could provide atomic arrangements in their crystal structures suitable for
      the epitaxy of apatite crystals, and anatase had better apatite-forming ability
      than rutile. XPS and Raman results revealed that this apatite layer was a
      carbonated and non-stoichiometric apatite with Ca/P ratio of 1.53, which was
      similar to the human bone. The formation of apatite on 600 degrees C heat-treated
      NiTi following immersion in SBF for 3 days indicated that the surface modified
      NiTi possessed excellent bioactivity.

PMID- 15941584
TI  - Preparation and characterization of polymeric coatings with combined nitric oxide
      release and immobilized active heparin.
AB  - A new dual acting polymeric coating is described that combines nitric oxide (NO)
      release with surface-bound active heparin, with the aim of mimicking the
      nonthrombogenic properties of the endothelial cell (EC) layer that lines the
      inner wall of healthy blood vessels. A trilayer membrane configuration is
      employed to create the proposed blood compatible coating. A given polymeric
      substrate (e.g., the outer surface of a catheter sleeve, etc.) is first coated
      with a dense polymer layer, followed by a plasticized poly(vinyl chloride) (PVC)
      or polyurethane (PU) layer doped with a lipophilic N-diazeniumdiolate as the NO
      donor species. Finally, an outer aminated polymer layer is applied. Porcine
      heparin is then covalently linked to the outer layer via formation of amide
      bonds. The surface-bound heparin is shown to possess anti-coagulant activity in
      the range of 4.80-6.39 mIU/cm2 as determined by a chromogenic anti-Factor Xa
      assay. Further, the surface NO flux from the underlying polymer layer containing
      the diazeniumdiolate species can be controlled and maintained at various levels
      (from 0.5 to 60 x 10(-10) mol cm(-2)min(-1)) for at least 24 h and up to 1 week
      (depending on the flux level desired) by changing the chemical/polymer
      composition of the NO release layer. The proposed polymeric coatings are capable
      of functioning by two complementary anti-thrombotic mechanisms, one based on the
      potent anti-platelet activity of NO, and the other the result of the ability of
      immobilized heparin to inhibit Factor Xa and thrombin (Factor IIa). Thus, the
      proposed polymeric coatings are expected to exhibit greatly enhanced
      thromboresistivity compared to polymers that utilize either immobilized heparin
      or NO release alone.

PMID- 15941585
TI  - Adhesion strength of human tenocytes to extracellular matrix component-modified
      poly(DL-lactide-co-glycolide) substrates.
AB  - We report a direct measurement of the adhesion strength of human embryonic
      tenocytes (HETCs) and transformed human embryonic tenocytes (THETCs) to
      fibronectin (FN)- and type I collagen (CNI)- modified poly(DL-lactide-co
      glycolide) (PLGA) substrates with a micropipette aspiration technique. PLGA
      substrates were first coated with poly-D-lysine (PDL), and then with various
      concentrations (1 microg/ml, 2 microg/ml, 5 microg/ml, and 10 microg/ml) of FN
      and CNI in serum-free F12 media. Anti-FN and Anti-CNI antibodies were used to
      inhibit attachment of tenocytes to FN- and CNI- modified substrates in a dilution
      range of 1:5000-1:500 and 1:1500-1:250, respectively. The substrates were
      employed for incubation of HETCs and THETCs for 30 min at 37 degrees C before the
      adhesion strength measurements. We found that the adhesion strengths showed a
      strong dependence on the seeding time and FN or CNI concentrations. Anti-FN and
      Anti-CNI antibodies significantly compromised adhesion of HETCs and THETCs to the
      corresponding modified substrates (P < 0.05). These findings show that FN- or CNI
      modified polymer substrates offer significant advantages for tissue engineering
      tendon scaffolds concerning tenocyte adhesion. In addition, HETCs and THETCs bear
      similar biological behaviors in terms of adhesion, indicating the possibility of
      using THETCs in place of HETCs in tissue engineering construction of human
      tendons.

PMID- 15941586
TI  - Transplantation of human acute myeloid leukemia (AML) cells in immunodeficient
      mice reveals altered cell surface phenotypes and expression of human endothelial
      markers.
AB  - To better characterize acute myeloid leukemia (AML) development in non-obese
      diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we transplanted
      samples from patients with AML or KG-1 and EOL-1 cell lines. We found 9/12
      primary AML samples and both cell lines to engraft within 2-8 weeks, with 5-80%
      human cells in bone marrow. Compared with freshly isolated AML cells, percentages
      of human CD33+, CD38+, CD31+ CD13+ or CD15+ subpopulations increased after
      transplantation, whereas percentages of CD34+ cells decreased. Engrafted mice
      frequently showed expression of human endothelial cell markers. Thus,
      transplantation of human AML into NOD/SCID mice reveals expression of
      hematopoietic and endothelial differentiation markers.

PMID- 15941587
TI  - A new plasmid vector for regulated gene expression in Bacillus subtilis.
AB  - We have developed a novel regulated expression vector for Bacillus subtilis based
      on the Staphylococcus aureus plasmid pUB110. This vector, named pPR54, carries
      the P(R) promoter and the cI857 gene (encoding a temperature-sensitive
      transcriptional repressor) from the Escherichia coli phage lambda. Using the gfp
      gene from the jellyfish Aequorea victoria as a reporter, we show that pPR54 is a
      useful vector for controllable production of heterologous proteins in B.
      subtilis.

PMID- 15941588
TI  - Chromosomal aberrations and frequency of micronuclei in sheep subchronically
      exposed to the fungicide Euparen Multi (tolylfluanid).
AB  - We analyzed chromosome aberrations, micronucleus frequency, mitotic index (MI),
      and nuclear division index (NDI) in peripheral lymphocytes of sheep
      subchronically exposed to the fungicide Euparen Multi (containing 50%
      tolylfluanid). Euparen Multi was administered by rumen sonde to group of Merino
      sheep (seven sheep/group) at 93 mg/kg body weight (1/20 LD50) daily for 28 days
      to assess its genotoxic effects. The frequencies of aberrant cells (ABC) in the
      experimental and control groups were 5.50+/-1.38% and 2.40+/-1.14%, respectively,
      and the increase in ABC in the treated group was significant (P = 0.003).
      Significantly increased numbers of chromatid breaks (5.67+/-1.21% against 2.40+/
      1.14%; P = 0.001), chromatid gaps (10.33+/-2.73% against 4.00+/-1.23%; P =
      0.001), and chromosome gaps (1.83+/-0.75% against 0.80+/-0.45%; P = 0.025) and
      exchanges (3.17+/-1.94% against 0.20+/-0.45%; P = 0.009) were observed in exposed
      animals in comparison to control animals. The frequency of micronuclei (MN) was
      29.40+/-5.86 per 1000 binucleated cells in peripheral lymphocytes of sheep in the
      control group and 49.57+/-19.12 per 1000 binucleated cells in the treated group.
      A significant increase in the frequency of MN in peripheral lymphocytes also was
      observed between the two groups (P = 0.0477). No statistical differences in MI
      and NDI values were found in the groups (P = 0.181 and 0.761, respectively).
      Thus, our results suggest that exposure to Euparen Multi may cause genome damage
      in somatic cells.

PMID- 15941589
TI  - Analysis of IgE and IgG B-cell immunodominant regions of Ole e 1, the main
      allergen from olive pollen.
AB  - Ole e 1 is a major allergen from olive pollen with an IgE-binding frequency
      around 80% among allergic population. Its diagnostic value has been demonstrated,
      and cross-reactive allergens have been found in ash, lilac and privet. We sought
      to determine IgE- and IgG-binding regions of Ole e 1. Ole e 1-specific polyclonal
      antiserum and sera from patients allergic to olive pollen were used to analyze
      IgG and IgE epitopes, respectively. Short overlapping synthetic peptides covering
      the complete sequence of Ole e 1 and point mutants of these peptides bound to
      membranes, as well as long recombinant peptides fused to GST were used in dot
      blot immunostaining and ELISA. Skin prick tests were performed on 14 allergic
      patients to assay the response in vivo to the recombinant fusion peptides.
      Residues at positions 8-11, 29, 32, 33, 55-59, 70, 107-110, 112, 120, 123, 141 of
      Ole e 1 sequence were found to be antigenically relevant in the IgG-binding.
      Although amino acids K137, L138, G139, Y141 and P142 were involved in the IgE
      recognition of a pool of sera from allergic individuals, the response to the IgEs
      seemed to be preferentially conformational. IgE-binding capability of recombinant
      GST-fused peptide T114-M145 was demonstrated by in vivo (prick test) and in vitro
      (ELISA) experiments. Major IgG and IgE-binding regions of Ole e 1 have been
      identified being the C-terminal an immunodominant region. These data could help
      to design hypoallergenic forms of the allergen.

PMID- 15941590
TI  - Effects of lead on learning in herring gulls: an avian wildlife model for
      neurobehavioral deficits.
AB  - Lead is one of the most common metals in contaminated ecosystems. Although lead
      poisoning and mortality have long been known, little is known of the
      neurobehavioral effects produced by low levels of lead in wild animals. Herein we
      describe the neurobehavioral effects of lead on learning using herring gulls
      (Larus argentatus) as a model. Doses used in these studies conducted in the
      laboratory and in nature were sufficient to produce lead concentrations in
      feathers that were equivalent to those found in gulls living in the wild. The
      exposure consisted of a single intraperitoneal injection of 0 and 100mg/kg lead
      acetate on day 2; each experiment involved 20-30 chicks in a lead-exposed group,
      and 20-30 chicks in a control group. We examined walking, begging, feeding,
      behavioral thermoregulation, individual recognition, and treadmill learning.
      There were significant differences between control and lead-exposed gulls chicks
      on all testing days. Learning, as well as improvement of motor skills, was faster
      for control chicks than lead-injected chicks for the thermoregulatory test,
      individual recognition, and behavior on a treadmill. Lead-injected chicks
      improved faster than control chicks only for walking scores. In a test where
      chicks were shown food under a cup, and then tested with three overturned cups,
      lead-exposed chicks did not show much improvement, whereas control chicks quickly
      learned where the food was located. The greatest differences in improvement were
      on the behavioral thermoregulation test, where lead-exposed chicks showed no
      improvement with age. Overall, this series of experiments indicated that for
      tasks involving learning, the disparity in accuracy and ability remained
      regardless of the number of days since exposure-control chicks sometimes improved
      and learned quicker than did lead-exposed chicks.

PMID- 15941591
TI  - Natural killer and dendritic cell liaison: recent insights and open questions.
AB  - The functional links between natural killer (NK) and dendritic cells (DCs) have
      been widely investigated in the last years and different studies have
      demonstrated that reciprocal activations ensue upon NK/DC interactions. More
      recently, the anatomical sites were these interactions take place have been
      identified together with the related cell subsets involved. Remarkably, as
      predicted by pioneering studies, there is now "in vivo" evidence that this
      cellular cross-talk occurring during the innate phase of the immune response can
      deeply affects the magnitude and the quality of the subsequent adaptive response.
      Thus, NK cells are not merely cytotoxic lymphocytes competent in containing viral
      and tumor spreading but can now rather be considered as crucial fine-tuning
      effector cells. Despite the large mass of information rapidly obtained in this
      field, several fundamental questions still remain to be addressed. Among them,
      two central issues require additional consideration: (a) what mediates the
      activation of NK cell cytotoxicity induced by DCs and (b) what factors are
      responsible for NK-dependent maturation of DCs. Unexpectedly, for both of these
      questions insufficient or inconsistent results are so far available; factors
      either dependent or independent from cell contacts between DCs and NK cells have
      been convincingly described, and it is likely that several mechanisms, rather
      than a single one, are responsible for each of these novel innate functions.
      Understanding the molecular bases of this complex liaison will pave the way to
      new and more effective immune adjuvants. The most recent advances about NK/DC
      interplay are here reviewed and possible answers to still open questions in this
      field are considered.

PMID- 15941592
TI  - Close encounters of different kinds: dendritic cells and gamma delta T cells
      heighten therapeutic applications.

PMID- 15941593
TI  - Factors influencing the presence of otitis media with effusion 16 months after
      initial diagnosis in a cohort of school-age children in rural Greece: a
      prospective study.
AB  - OBJECTIVE: Few studies have specifically assessed the risk factors for
      persistence or recurrence of OME in a cohort of school-age children. The
      generally accepted etiological factors for OME occurrence may not apply in the
      same way when the presence of OME over a year from original diagnosis is
      assessed. METHODS: A cohort of 250 school-age children with unilateral or
      bilateral OME, identified through screening of 5121 asymptomatic children was re
      examined 16 months later. All were assessed for a variety of demographic, family
      and medical factors. Measures included tympanometry, acoustic reflexes and a
      complete otolaryngologic examination. RESULTS: At 16 months after initial
      confirmation of OME, 56 out of 250 children (22.4%) suffered from OME, 21
      bilateral and 31 unilateral. Presence of OME at 16 months was not associated with
      gender, blood group, gestational age and weight, history of breast feeding,
      paternal education level and smoking history, history of allergy, previous use of
      antibiotics, or with surgery (myringotomy, insertion of ventilation tubes or
      adenotonsillectomy). In multiple backward-eliminating logistic regression, the
      only factors associated with OME presence after 16 months were episodes of AOM
      during the study period (odds ratio 2.75 (95% CI: 1.13-8.17), p=0.04) and younger
      age (odds ratio 0.53 (95% CI: 0.32-0.79), p=0.002 for each 2 years of increase in
      age). CONCLUSION: Seventy-eight percent of school-age children identified with
      OME through screening will be free of disease 16 months later. The threshold for
      referral, or surveillance could however justifiably be lower in children who (a)
      have once been identified with OME and (b) are (relatively) younger, or have
      experienced an episode of acute otitis media.

PMID- 15941595
TI  - Formation of in vivo tissue engineered human hyaline cartilage in the shape of a
      trachea with internal support.
AB  - OBJECTIVE: Treatment and management of congenital as well as post-traumatic
      trachea stenosis remains a challenge in pediatric surgery. The aim of this study
      was to reconstruct a trachea with human nasal septum chondrocytes by using the
      combination of biodegradable hydrogel and non-biodegradable high-density
      polyethylene (HDP) as the internal predetermined shape scaffold. METHODS: Human
      nasal septum cartilage was harvested as excessive tissue after elective
      septoplasty and digested in 0.6% collagenase II. Chondrocytes were cultured in an
      equal volume mix of Ham's F12 medium and Dulbecco's modified eagle medium added
      with 10% fetal bovine serum and basic fibroblast growth factor. After two
      passages, the cultured chondrocytes were trypsinized and mixed with biodegradable
      hydrogel Pluronic F127. The chondrocytes-hydrogel admixture was then painted over
      the HDP as the internal support in a predetermined trachea shape. The composite
      was then implanted subcutaneously in athymic mice. RESULTS: After 8 weeks of in
      vivo implantation, the tissue engineered trachea constructs were harvested.
      Macroscopic appearance of the tissue engineered trachea constructs demonstrated
      that the HDP were 80-90% covered with yellowish glistering cartilage like tissue
      without any sign of inflammation. The tissue engineered trachea cartilage
      consisted of evenly spaced lacunae embedded in basophilic matrix and stained red
      with Safranin-O staining denoting abundant proteoglycans production. Type II
      collagen gene which was expressed in native cartilage was highly expressed in
      this tissue engineered trachea cartilage. CONCLUSION: We have successfully
      reconstructed a trachea in vivo with human nasal septum chondrocytes using HDP as
      the internal support. This construct has the advantage of bio-inert and strength
      in which both are important properties in tracheal reconstruction.

PMID- 15941596
TI  - Dengue typing assay based on real-time PCR using SYBR Green I.
AB  - Typing of dengue virus is crucial for the epidemiology and pathogenesis of dengue
      virus infection. Hence, highly sensitive and accurate diagnostic tools are
      essential. The purpose of this study was to identify all four types of dengue
      virus based on the 3'-untranslated region of the virus by melting curve analysis
      and real-time PCR using SYBR Green I. The types obtained by this method were
      compared with the results of direct sequencing of 39 serum or plasma samples of
      patients with clinical dengue infection that included a positive tourniquet test,
      thrombocytopenia and positive dengue IgM antibody. The accuracy of typing by
      melting curve analysis was 97.4%. In conclusion, real-time PCR and melting curve
      analysis using one single-primer pair were shown to be highly efficient for clear
      detection and typing of dengue virus in clinical specimens. This method therefore
      represents a simple, sensitive, specific, rapid and economic method, which will
      be essential for epidemiological studies of dengue virus infection.

PMID- 15941597
TI  - Modification of a viral envelope glycoprotein cell-cell fusion assay by utilizing
      plasmid encoded bacteriophage RNA polymerase.
AB  - Many viruses enter cells via an interaction of the viral envelope glycoprotein
      (Env) with receptor inducing fusion of viral and cellular membranes. These
      interactions are often evaluated in cell-cell fusion, gene-reporting systems with
      effector cells expressing Env and target cells expressing receptors. A common
      system utilizes vaccinia virus encoding T7 RNA polymerase (RNAP) in effector
      cells and a T7 promoted reporter plasmid in target cells. Fusion is quantified
      with expression of the reporter plasmid. However, direct activation of reporter
      plasmid from vaccinia virus can occur increasing background activity. We report
      here a modification of this assay in which T7 RNAP is expressed from a plasmid
      rather than vaccinia. This modification increased sensitivity with a ten-fold
      reduction in background. A novel dual T7/SP6 RNAP fusion assay was also developed
      to allow rapid screening for functional Env clones. Using these assays, we show
      that Envs from two CD4-independent HIV-2 isolates (VCP and ROD/B), which are able
      to fuse with chemokine receptor CXCR4 in a CD4-independent manner, are also able
      to fuse with alternative coreceptors GPR1 and GPR15 in the absence of CD4. The
      assay could also detect fusion of murine leukemia virus on target cells
      expressing the ecotropic MCAT-1 receptor showing its broad utility in other viral
      systems.

PMID- 15941598
TI  - Swim-test as a function of motor impairment in MPTP model of Parkinson's disease:
      a comparative study in two mouse strains.
AB  - Parkinson's disease (PD) is a common neurodegenerative disease that exhibits
      motor dysfunctions, such as tremor, akinesia and rigidity. In the present study,
      we investigated whether swim-test could be used as one of the behavioural
      monitoring techniques to study motor disability in 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP)-induced parkinsonism in two mouse strains, Balb/c and
      C57BL/6. Mice were treated with different doses of MPTP (10, 20 and 30 mg/kg,
      twice, 16 h apart), and were subjected to swim-test on the third day of the first
      MPTP injection. MPTP-induced tremor was monitored at 30 min, and akinesia and
      rigidity developed were studied 3 h after the second MPTP treatment. While tremor
      and akinesia produced were dose-dependent and the intensity of tremor was
      comparable in the two strains of mice studied, the latter response in C57BL/6 was
      significantly lesser than that observed in Balb/c. Rigidity exhibited in Balb/c
      mice were dose-dependent, but not in C57BL/6. There was observed an inverse
      relationship between swim-score and the doses of MPTP in both the strains. MPTP
      caused a significant and dose-dependent reduction in striatal dopamine level in
      both the strains of mice, when assayed on the fourth day employing an HPLC with
      electrochemical detector. A significant positive correlation existed (r = 0.94
      for Balb/c and r = 0.82 for C57BL/6) for the striatal dopamine-depletion and the
      swim-score in the MPTP-treated mice. While swim deficit and striatal dopamine
      loss were long lasting (till the third week) in C57BL/6, in Balb/c mice the motor
      deficit showed recovery by the second week. In these animals, a significant
      attenuation in striatal dopamine loss was observed by the third week. These
      results indicate that swim ability is directly proportional to striatal dopamine
      content, and suggest that swim-test could be used as a major technique to monitor
      motor dysfunction in experimental animals.

PMID- 15941599
TI  - Prenatal stress produces more behavioral alterations than maternal separation in
      the elevated plus-maze and in the elevated T-maze.
AB  - Prenatal stress and maternal separation are used in a large number of studies on
      early adversity consequences and present some similarities in their effects. The
      present work investigates the behavioral effects of these two procedures on two
      models of anxiety: the elevated plus-maze and the elevated T-maze. During
      pregnancy, female rats were submitted to uncontrollable electric foot shock
      sessions every other day or kept undisturbed. After delivery, litters from
      undisturbed dams were submitted to either 180-min daily periods of maternal
      separations from the 3-14th postnatal days or maintained with the dams all the
      time. Litters from the stressed dams were left undisturbed from the 3-14th
      postnatal days. Only males were tested. In adulthood, rats were tested in the
      elevated T-maze or in the elevated plus-maze. In the latter procedure half the
      subjects were submitted to a 60-min period of restraint immediately before being
      tested. The following measures were taken in the elevated plus-maze: frequency
      and time spent in entries into the arms, stretching, rearing, grooming and head
      dipping. In the T-maze measures of avoidance and escape latencies were used. Our
      data indicated that prenatal stress had more pronounced anxiogenic effects than
      maternal separation, as judged by reduced exploration of the open arms of the
      elevated plus-maze, but mainly after the restraint stress, and increase in
      avoidance latencies in the elevated T-maze. The other measures not directly
      involved in the elevated plus-maze arm exploration yielded similar results. Our
      data indicate that prenatal stress causes more anxiogenic effects in adulthood
      than maternal separation but, in the elevated plus-maze, these anxiogenic effects
      are better seen immediately after an acute stress.

PMID- 15941600
TI  - Decreased proliferation in the adult rat hippocampus after exposure to the Morris
      water maze and its reversal by fluoxetine.
AB  - Granular cell proliferation in the adult hippocampus decreases during aging and
      after chronic stress, while it can be increased by physical activity or treatment
      with the antidepressant fluoxetine. We investigated whether the physical and
      cognitive stimulation accompanied by stress in the commonly used Morris water
      maze affects the rate of proliferation and whether the induced changes can be
      influenced by antidepressant treatment with fluoxetine. Proliferating cells in
      the dentate gyrus were labeled by three injections of BrdU during the 24h
      preceding sacrifice. Early differentiation to neuronal progeny was studied by
      immunohistochemical staining for doublecortin (DCX), a microtubule binding
      protein expressed in newborn neurons. Acquisition learning in the water maze for
      15 days caused a significant decrease in granular cell proliferation in the
      granular cell layer of the hippocampus. The decrease in the number of BrdU- and
      DCX-positive cells was reversed to control levels by the use of fluoxetine during
      the water maze training. Fluoxetine treatment alone increased the number of BrdU
      positive cells, but did not increase the number of DCX-positive cells. We
      conclude that the exposure of adult male rats to water maze acquisition trials is
      a stressful experience that significantly suppresses the production of new
      granular cells and that this stressful effect can be blocked by the concomitant
      administration of the antidepressant fluoxetine.

PMID- 15941601
TI  - Behavioral, cognitive and biochemical responses to different environmental
      conditions in male Ts65Dn mice, a model of Down syndrome.
AB  - Ts65Dn mouse is the most widely accepted model for Down syndrome. We previously
      showed that environmental enrichment improved spatial learning in female but
      deteriorated it in male Ts65Dn mice. This study analyzed the factors contributing
      to the disturbed cognition of male Ts65Dn mice after enriched housing, by
      allocating male control and Ts65Dn mice in four conditions after weaning: small
      (n = 2-3) and large group (n = 8-10) housing, and enriched housing in small (2-3)
      and large groups (8-10). Learning, aggressive behavior, anxiety-like behavior and
      biochemical correlates of stress were evaluated when Ts65Dn and control mice were
      4-5 months old. Environmental enrichment in large mixed colonies of Ts65Dn and
      diploid littermates disturbed behavioral and learning skills of Ts65Dn mice in
      the Morris water maze. ACTH and testosterone levels were not modified in any
      group of mice. Ts65Dn and control mice subjected to enriched housing in large
      groups and Ts65Dn mice housed in large groups showed higher corticosterone
      levels. Aggressive behavior was evaluated by measuring the number of attacks
      performed in the presence of an intruder. Ts65Dn mice performed less attacks than
      controls in all conditions, especially after enriched housing, indicating
      subordination. In the plus maze, cognitive aspects (i.e. risk assessment) and
      motor components (open arm avoidance) of anxiety behavior were evaluated; no
      difference in any condition was found. It is suggested that an excess of social
      and/or physical stimulation in Ts65Dn mice may affect cognition by disturbing the
      emotional and behavioral components of the learning process.

PMID- 15941602
TI  - Lateralized fish perform better than nonlateralized fish in spatial reorientation
      tasks.
AB  - Lines of fish (Girardinus falcatus) obtained through selective breeding showing
      different degree and direction of behavioural lateralization in a variety of
      tasks were tested for their ability for spatial reorientation. In the first
      experiment, fish were required to reorient themselves after passive
      disorientation in a rectangular tank in the presence of a salient feature (a blue
      wall). Lateralized fish proved to be better than nonlateralized fish at using the
      geometric cues provided by the shape of the tank in order to disambiguate between
      corners with similar featural information. In the second experiment fish were
      tested in a square-shaped tank (in order to eliminate any geometric cues) in the
      presence of salient features (panels) located at the corners. Lateralized fish
      proved better than nonlateralized fish in using featural cues to reorient
      themselves. These findings suggest that lateralization may confer advantages in
      spatial reorientation based on the use of geometric and nongeometric cues.

PMID- 15941603
TI  - Allelic segregation and independent assortment in T. brucei crosses: proof that
      the genetic system is Mendelian and involves meiosis.
AB  - The genetic system on Trypanosoma brucei has been analysed by generating large
      numbers of independent progeny clones from two crosses, one between two cloned
      isolates of Trypanosoma brucei brucei and one between cloned isolates of T. b.
      brucei and Trypanosoma brucei gambiense, Type 2. Micro and minisatellite markers
      (located on each of the 11 megabase housekeeping chromosomes) were identified,
      that are heterozygous in one or more of the parental strains and the segregation
      of alleles at each locus was then determined in each of the progeny clones. The
      results unequivocally show that alleles segregate in the predicted ratios and
      that alleles at loci on different chromosomes segregate independently. These data
      provide statistically robust proof that the genetic system is Mendelian and that
      meiosis occurs. Segregation distortion is observed with the minisatellite locus
      located on chromosome I of T. b. gambiense Type 2 and neighboring markers, but
      analysis of markers further along this chromosome did not show distortion leading
      to the conclusion that this is due to selection acting on one part of this
      chromosome. The results obtained are discussed in relation to previously proposed
      models of mating and support the occurrence of meiosis to form haploid gametes
      that then fuse to form the diploid progeny in a single round of mating.

PMID- 15941604
TI  - An insulator-based (electrodeless) dielectrophoretic concentrator for microbes in
      water.
AB  - Dielectrophoresis (DEP), the motion of a particle caused by an applied electric
      field gradient, can concentrate microorganisms non-destructively. In insulator
      based dielectrophoresis (iDEP) insulating microstructures produce non-uniform
      electric fields to drive DEP in microsystems. This article describes the
      performance of an iDEP device in removing and concentrating bacterial cells,
      spores and viruses while operated with a DC applied electric field and pressure
      gradient. Such a device can selectively trap particles when dielectrophoresis
      overcomes electrokinesis or advection. The dielectrophoretic trapping behavior of
      labeled microorganisms in a glass-etched iDEP device was observed over a wide
      range of DC applied electric fields. When fields higher than a particle-specific
      threshold are applied, particles are reversibly trapped in the device.
      Experiments with Bacillus subtilis spores and the Tobacco Mosaic Virus (TMV)
      exhibited higher trapping thresholds than those of bacterial cells. The iDEP
      device was characterized in terms of concentration factor and removal efficiency.
      Under the experimental conditions used in this study with an initial dilution of
      1 x 105 cells/ml, concentration factors of the order of 3000x and removal
      efficiencies approaching 100% were observed with Escherichia coli cells. These
      results are the first characterization of an iDEP device for the concentration
      and removal of microbes in water.

PMID- 15941605
TI  - 3-Hydroxy fatty acids in saliva as diagnostic markers in chronic periodontitis.
AB  - Saturated straight- and branched-chain 3-hydroxy fatty acids (3-OH FAs) of 10-18
      carbon chain lengths were determined in saliva from 27 individuals with chronic
      periodontitis and 18 healthy individuals by using gas chromatography-tandem mass
      spectrometry. Of the 14 different 3-OH FAs detected, 3-OH-C(i17:0) was the most
      abundant in the periodontitis samples while 3-OH-C(14:0) was the most abundant in
      the healthy individuals. Considering the relative percentages of 3-OH-C(12:0), 3
      OH-C(14:0), 3-OH-C(i17:0), and 3-OH-C(17:0), 95.6% of all cases were correctly
      classified as healthy individuals or periodontitis patients by means of
      discriminant analysis. The sensitivity, specificity, positive predictive value
      and negative predictive value of 3-OH FA analysis in diagnosing peridontitis
      were, respectively, 0.92, 1.00, 1.00, and 0.90. The results indicate that 3-OH FA
      analysis of saliva samples is a useful diagnostic method in chronic
      periodontitis.

PMID- 15941606
TI  - Real time measurement and control of thermodynamic water activities for enzymatic
      catalysis in hexane.
AB  - The esterification reaction of geraniol with acetic acid catalyzed by immobilized
      Candida antarctica lipase B was studied in hexane using a pervaporation-assisted
      batch reactor. The effect of thermodynamic water activity (a(w)) on the initial
      reaction rate was investigated at a(w) ranging from 0.02 to 1.0. The a(w) was
      monitored on-line in real time. a(w) was actively controlled throughout the
      reaction by using highly water-selective membrane pervaporation. This novel
      combination of a(w) sensing and control eliminates changes in a(w) during the
      reaction even in the initial phase of relatively rapid water release during an
      esterification. No chemicals are introduced for a(w) control, and no purge gases
      or liquids are needed. A maximum in the initial reaction rate was found
      approximately at a(w)=0.1. The initial reaction rate declined quickly at higher
      a(w), and dropped precipitously at lower a(w).

PMID- 15941607
TI  - Pleurostrin, an antifungal peptide from the oyster mushroom.
AB  - A 7kDa peptide, with inhibitory activity on mycelial growth in the fungi
      Fusaerium oxysporum, Mycosphaerella arachidicola and Physalospora piricola, was
      isolated from fresh fruiting bodies of the oyster mushroom. The isolation
      procedure entailed extraction with an aqueous buffer, ion exchange chromatography
      on DEAE-cellulose, affinity chromatography on Affi-gel blue gel and gel
      filtration by fast protein liquid chromatography on Superdex 75. The protein was
      unadsorbed on DEAE-cellulose and adsorbed on Affi-gel blue gel. It demonstrated
      an N-terminal sequence different from known antifungal proteins and peptides.

PMID- 15941608
TI  - Impact of haloperidol and risperidone on gene expression profile in the rat
      cortex.
AB  - Despite the clinical efficacy of the most thoroughly studied conventional
      neuroleptic agent haloperidol, and the atypical antipsychotic risperidone is well
      established, little information is available on their molecular effects. Recent
      advances in high-density DNA microarray techniques allow the possibility to
      analyze thousands of genes simultaneously for their differential gene expression
      patterns in various biological processes, and to determine mechanisms of drug
      action. The aim of this series of experiments was to gain experience in
      antipsychotic gene-expression profiling and characterize (in the parlance of
      genomics) the "antipsychotic transcriptome." In this prospective animal study,
      broad-scale gene expression profiles were characterized for brains of rats
      treated with antipsychotics and compared with those of sham controls. We used DNA
      microarrays containing 8000 sequences to measure the expression patterns of
      multiple genes in rat fronto-temporo-parietal cortex after intraperitoneal
      treatment with haloperidol or risperidone. A number of transcripts were
      differentially expressed between control and treated samples, of which only 36
      and 89 were found to significantly differ in expression as a result of exposure
      to haloperidol or risperidone, respectively (P<0.05). Acutely, 13 genes were more
      highly expressed and 15 transcripts were found to be significantly less abundant,
      whereas chronically nine genes were up-regulated and none of them was repressed
      in haloperidol-treated cortices. Risperidone acutely induced 43 and repressed 46
      genes, and chronically over-expressed 6 and down-regulated 11 transcripts.
      Selected genes were assayed by real-time PCR, then normalized to beta-actin.
      These assays confirmed the significance of the array results for all transcripts
      tested. Despite their differing receptor affinity and selectivity, our findings
      indicate that haloperidol and risperidone interfere with cell survival, neural
      plasticity, signal transduction, ionic homeostasis and metabolism in a similar
      manner.

PMID- 15941610
TI  - Conservative treatment of prolonged bilateral mandibular dislocation with the
      help of an intermaxillary fixation screw.

PMID- 15941609
TI  - Decreased phosphatidylethanolamine binding protein expression correlates with
      Abeta accumulation in the Tg2576 mouse model of Alzheimer's disease.
AB  - Phosphatidylethanolamine binding protein (PEBP) is a multifunctional protein,
      with proposed roles as the precursor protein of hippocampal cholinergic
      neurostimulating peptide (HCNP), and as the Raf kinase inhibitor protein (RKIP).
      Previous studies have demonstrated a decrease in PEBP mRNA in CA1 region of AD
      hippocampus. The current study demonstrates that PEBP is decreased in the
      hippocampus of 11 month Tg2576 mice, in the absence of change in mRNA levels
      compared to non-transgenic littermates. The level of PEBP in transgenic mouse
      hippocampus significantly decreases at 11 months (a time point when Abeta begins
      accumulating) and 15 months (when Abeta plaques have formed). There was a
      significant correlation between decreased PEBP expression and accumulation of
      Abeta. Immunohistochemical studies on Tg2576 and AD brain sections demonstrate
      that PEBP immunoreactivities are present at the periphery of dense multicore
      Abeta plaques, and in selective astrocytes, primarily surrounding plaques. These
      findings suggest that PEBP expression may be influenced by accumulation of Abeta.
      Down-regulation of PEBP may result in lower levels of HCNP or altered
      coordination of signal transduction pathways that may contribute to neuronal
      dysfunction and pathogenesis in AD.

PMID- 15941611
TI  - Dissolved oxygen and dietary phosphorus modulate utilization and effluent
      partitioning of phosphorus in rainbow trout (Oncorhynchus mykiss) aquaculture.
AB  - Phosphorus (P) is the limiting nutrient in freshwater primary production, and
      excessive levels cause premature eutrophication. P levels in aquaculture
      effluents are now tightly regulated. Increasing our understanding of waste P
      partitioning into soluble, particulate, and settleable fractions is important in
      the management of effluent P. When water supply is limited, dissolved oxygen
      concentration (DO) decreases below the optimum levels. Therefore, we studied
      effects of DO (6 and 10mg/L) and dietary P (0.7 and 1.0% P) on rainbow trout
      growth, P utilization, and effluent P partitioning. Biomass increased by 40%
      after 3 weeks. DO at 10mg/L significantly increased fish growth and feed
      efficiency, and increased the amount of P in the soluble fraction of the
      effluent. Soluble effluent P was greater in fish fed 1.0% P. DO increases fish
      growth and modulates P partitioning in aquaculture effluent.

PMID- 15941612
TI  - Mental health and hostility as predictors of temporary employment: evidence from
      two prospective studies.
AB  - We used two studies to examine whether mental health and hostility predicted
      temporary employment. Study 1 involved a cohort of 970 Finnish hospital employees
      (102 men, 868 women) who had temporary job contracts at baseline. After
      adjustment for demographics, organisational tenure and part-time work status,
      doctor-diagnosed psychiatric disorder predicted continuing in temporary
      employment instead of receiving a permanent job by the end of the 2-year follow
      up. A higher level of hostility was also associated with temporary employment,
      but only among employees in low socioeconomic positions. In Study 2, anxiety and
      aggressive behaviour were measured in a cohort of 226 Finnish school children
      (116 boys, 110 girls) at 8 years of age. Anxiety in childhood predicted temporary
      employment at age 42. Aggressive behaviour in childhood was related to ongoing
      temporary employment status in adulthood among individuals in low socioeconomic
      positions. Our findings suggest that selection by individual characteristics
      operates between the temporary and permanent workforces. Mental health problems,
      a part of which are already seen in childhood, seem to restrict individuals'
      possibilities to gain secure labour market positions. Hostility and
      aggressiveness seem to be related to labour market prospects only among
      individuals in low socioeconomic positions.

PMID- 15941613
TI  - Challenges and changes in spirituality among doctors who become patients.
AB  - Though spirituality can help patients cope with illness, several studies have
      suggested that physicians view spirituality differently than do patients. These
      issues have not been systematically investigated among doctors who become
      patients, and who may be able to shed critical light on this area. We interviewed
      fifty doctors from major urban US centers who had become patients due to serious
      illnesses about their experiences and views relating to religion and spirituality
      before and after diagnosis, and we explore the range of issues that emerged.
      These physician-patients revealed continua of forms and contents of spirituality.
      The forms ranged from being spiritual to start with; to being spiritual, but not
      thinking of themselves as such; to wanting but being unable to believe. Some
      continued to doubt and, perhaps relatedly, appeared depressed. The contents of
      beliefs ranged from established religious traditions, to mixing beliefs, or
      having non-specific beliefs (e.g., concerning the power of nature). One group of
      doctors felt wary of organized religion, which could prove an obstacle to belief.
      Others felt that symptoms could be reduced through prayer. At times, self
      assessments of spirituality were difficult to make or inaccurate. Questions
      surfaced concerning whether and how medical education could best address these
      issues, and how spirituality may affect clinical work. This study is the first
      that we know of to examine spirituality among physicians when they become
      patients. Obstacles to physicians' attentiveness to the potential role of
      spirituality arose that need to be further explored in medical education and
      future research. Increased awareness of these areas could potentially have
      clinical relevance, strengthening doctor-patient relationships and communication,
      and patient satisfaction.

PMID- 15941614
TI  - Effects of hypothyroidism induced by perinatal exposure to PTU on rat behavior
      and synaptic gene expression.
AB  - Hypothyroidism in the rat induced by perinatal exposure to propylthiouracil (PTU)
      is a useful animal model to study molecular changes underlying neurobehavioral
      defects associated with this condition. Understanding the developmental
      alterations in gene expression related to the neurobehavioral dysfunction should
      help to identify molecular markers for developmental neurotoxicity at an early
      stage of development. In the present study, we evaluate the effects of PTU on the
      expression of a set of genes implicated in neural network formation or synaptic
      function at a minimal dose of PTU causing behavioral alteration. Various doses of
      PTU were administered to dams from late pregnancy to the lactation period and the
      expression of selected genes in the hippocampus and the cerebral cortex of
      offspring was examined by quantitative RT-PCR. Behavioral performance of PTU
      treated rats was also assessed. PTU-treated rats showed increased motor activity
      and impairment of E-maze learning at weaning and after maturation. At doses
      causing such behavioral alteration, expression of GAP-43 and M1 mRNAs was changed
      during neuronal network formation, suggesting that levels of these factors during
      development are important for accurate postnatal development and function.

PMID- 15941615
TI  - Nuchal cord detected by ultrasound at term is associated with mode of delivery
      and perinatal outcome.
AB  - OBJECTIVES: To evaluate the clinical relevance of nuchal cord in normal, vertex,
      singleton pregnancies at term, and its effect on mode of delivery and perinatal
      outcome. STUDY DESIGN: Prospective study with 352 normal, singleton pregnancies,
      with fetuses in the vertex presentation, examined with real-time ultrasound at 37
      39 weeks. Health care workers at labour and delivery blinded to previous
      detection of nuchal cord. RESULTS: Fetuses of nulliparous women with a nuchal
      cord were more likely to be delivered with operative vaginal or caesarean
      delivery (n = 153, p < 0.0001). This was not the case with higher parity (n =
      199, p = 0.07). There was no difference between nuchal cord (n = 144) and control
      groups (n = 208) in amniotic fluid quantity at 37-39 weeks (p = 0.554) or
      intrapartum CTG (p = 0.9). On the other hand, nuchal cord group had lower Apgar
      scores at 1 and 5 min (p = 0.001 and 0.027 respectively); this difference
      remained significant when adjusted for birth weight (p = 0.001 and 0.016), but
      disappeared when adjusted for mode of delivery (p = 0.048 and 0.319).
      CONCLUSIONS: Nuchal cord in normal pregnancies at term is associated with
      increased rate of operative vaginal and caesarean delivery in nulliparae. The
      presence of a nuchal cord results in slightly lower Apgar scores at 1 and 5 min,
      mainly as a consequence of higher operative delivery rates.

PMID- 15941616
TI  - Metformin treatment of PCOS during adolescence and the reproductive period.
AB  - Insulin resistance is a common feature of PCOS. Hyperinsulinemia has been
      causally linked with all features of the syndrome, such as hyperandrogenism,
      reproductive disorders, and metabolic disturbances. Several insulin-sensitizing
      agents have been tested in the management of PCOS. Metformin is the only drug
      currently in widespread clinical use for PCOS. In a high percentage of patients,
      treatment with metformin is followed by regularization of the menstrual cycle,
      less pronounced hyperandrogenism and cardiovascular risk factors, and some
      improvement in the response to therapies aimed at induction of ovulation. In
      adolescent girls who are anovulatory and moderately obese, metformin
      administration can have a normalizing effect on multiple aberrations within the
      endocrine-metabolic status. During the reproductive period, metformin
      administration can improve reproductive function and the establishment of
      pregnancy. A role of metformin in prevention of gestational diabetes and
      hypertensive complications of pregnancy has yet to be shown. Finally, any real
      benefit of insulin-lowering treatment in terms of lesser cardiovascular risk in
      women with PCOS women remains to be demonstrated.

PMID- 15941617
TI  - A statistical analysis of the TRANSFAC database.
AB  - Transcription factors are key regulatory elements that control gene expression.
      The TRANSFAC database represents the largest repository for experimentally
      derived transcription factor binding sites (TFBS). Understanding TFBS, which are
      typically conserved during evolution, helps us identify genomic regions related
      to human health and disease, and regions that might be predictive of patient
      outcomes. Here we present a statistical analysis of all TFBS in the TRANSFAC
      database. Our analysis suggests that current definition of TFBS core regions in
      TRANSFAC should be re-examined so as to capture a more precise notion of "cores."
      We offer insight into more appropriate definitions of TFBS consensus sequences
      and core regions. These revised definitions provide a better understanding of the
      nature of transcription factor-DNA binding and assist with developing algorithms
      for de novo TFBS discovery as well as finding novel variants of known TFBS.

PMID- 15941618
TI  - OPA oxidation rates in supercritical water.
AB  - Supercritical water oxidation can effectively destroy a large variety of high
      risk wastes resulting from munitions demilitarization and complex industrial
      chemical. An important design consideration in the development of supercritical
      water oxidation is the information on the oxidation rate. In this paper, the
      oxidation rate of isopropyl amine (OPA), one of high-risk wastes resulting from
      munitions demilitarization, was investigated under supercritical water oxidation
      (SCWO) conditions in an isothermal tubular reactor. H2O2 was used as the oxidant.
      The reaction temperatures were ranged from 684 to 891 K and the residence times
      varied from 9 to 18s at a fixed pressure of 25 MPa. The conversion of OPA was
      monitored by analyzing total organic carbon (TOC) on the liquid effluent samples.
      The initial TOC concentrations of OPA varied from 7.21 to 143.78 mmol/l at the
      conversion efficiencies from 88.94 to 99.98%. By taking into account the
      dependence of reaction rate on oxidant and TOC concentration, a global power-law
      rate expression was regressed from 38 OPA experimental data. The resulting pre
      exponential factor was 2.46(+/-0.65)x10(3)l(1.37)mmol(-0.37)s(-1); the activation
      energy was 64.12+/-1.94 kJ/mol; and the reaction orders for OPA (based on TOC)
      and oxidant were 1.13+/-0.02 and 0.24+/-0.01, respectively.

PMID- 15941619
TI  - Adsorption behaviors of some phenolic compounds onto high specific area activated
      carbon cloth.
AB  - Adsorption of phenol, hydroquinone, m-cresol, p-cresol and p-nitrophenol from
      aqueous solutions onto high specific area activated carbon cloth has been
      studied. The effect of ionization on adsorption of these ionizable phenolic
      compounds was examined by studying the adsorption from acidic, basic and natural
      pH solutions. Kinetics of adsorption was followed by in situ UV spectroscopy over
      a period of 90 min. First-order rate law was found to be valid for the kinetics
      of adsorption processes and the rate constants were determined. The highest rate
      constants were obtained for the adsorption from solutions at the natural pH. The
      lowest rate constants were observed in basic solutions. The rate constants
      decreased in the order p-nitrophenol approximately m-cresol>p-cresol>hydroquinone
      approximately phenol. Adsorption isotherms were derived at 30 degrees C and the
      isotherm data were treated according to Langmuir, Freundlich and Tempkin isotherm
      equations. The goodness of fit of experimental data to these isotherm equations
      was tested and the parameters of equations were determined. The possible
      interactions of compounds with the carbon surface were discussed considering the
      charge of the surface and the possible ionization of compounds at acidic, basic
      and natural pH conditions.

PMID- 15941620
TI  - Respiratory and cardiovascular actions of orexin-A in mice.
AB  - Ample evidence has been reported to show a probable contribution of orexin in the
      central cardiovascular regulation. Although cardiovascular and respiratory
      centers in the brain are located close to each other and are interconnected, the
      possible participation of orexin in respiratory regulation has not been fully
      documented. Here we examined the effects of intracerebroventricular
      administration of orexin-A on respiratory and cardiovascular parameters in
      urethane-anesthetized mice. Respiratory frequency and tidal volume were recorded
      simultaneously with blood pressure and heart rate. Orexin-A (0.003-3 nmol in 2
      microL) or vehicle was administered into the lateral ventricle or cisterna magna.
      Lateral ventricular administration induced a rise in respiratory frequency (by
      11% at the highest dose), tidal volume (76%), blood pressure (13%) and heart rate
      (6%) in a dose-dependent manner. With intracisternal administration, however,
      respiratory frequency did not change while a similar increase in tidal volume
      (75%) was observed. A relatively larger cardiovascular response was elicited with
      intracisternal administration (blood pressure 26%, heart rate 9%). On the other
      hand, with either administration route, orexin-A did not affect reflex increases
      in respiratory frequency and tidal volume in response to hypoxia and hypercapnia.
      These results show possible participation of orexin-A not only in the
      cardiovascular regulation but also in the respiratory control system. Moreover,
      orexin can affect the cardiorespiratory control system at multiple sites in
      different ways. Orexin-A seems not to be involved in respiratory reflex
      regulation in mice at least under anesthetized condition.

PMID- 15941621
TI  - Generation of bone marrow-derived neural cells in serum-free monolayer culture.
AB  - Bone marrow-derived cells (BMCs) are reported to trans-differentiate into neural
      lineages, and are expected to offer a valuable resource for treating severe
      diseases of the central nervous system. BMCs that show neural differentiation may
      differ morphologically from typical marrow stromal cells. The present study aimed
      to obtain efficient generation of cells with neural features from bone marrow.
      Serum-free culture was applied to BMCs to prevent the growth of differentiated
      cells. Using basic fibroblast growth factor and extracellular matrix, rodent BMCs
      capable of proliferation and neural differentiation expanded in monolayer form.
      Cultured cells were small, round or spindle-shaped, and expressed nestin. Under
      neural differentiation conditions, cells developed long, thin cellular processes
      with branches, and expressed neuronal and glial phenotypes. Intracerebrally
      transplanted BMCs survived and migrated into the subcortex of syngenic animals.

PMID- 15941622
TI  - Differential expression of the truncated TrkB receptor, T1, in the primary motor
      and prefrontal cortices of the adult macaque monkey.
AB  - A truncated TrkB receptor, T1, which is one of the receptors for brain-derived
      neurotrophic factor, has been shown to regulate the morphology of neurons and
      glial cells in primary cultures and/or slices overexpressing T1 in the recent
      past. However, in vivo localization of T1 at protein level remains unclear. In
      the present study, we examined the localization of T1 in the primary motor and
      prefrontal cortices of adult monkeys by using immunohistochemistry. In the
      primary motor cortex, T1 immunoreactivity was observed mainly in the pyramidal
      neurons of layers II-VI, especially Betz cells of layer V. The apical and basal
      dendrites and cell bodies of Betz cells were strongly stained. In addition, we
      found that the interneurons were also T1-immunopositive and that there were no T1
      positive astrocytes. In the prefrontal cortex, we observed strong
      immunoreactivity of T1 in astrocytes as well as pyramidal neurons of layer V. The
      pyramidal neurons and interneurons in layers II/III were faintly immunoreactive
      for T1. Thus, these findings, together with the fact that T1 is involved in
      morphological control of neurons and glial cells, suggest that the prefrontal
      cortex might possess a different degree of morphological plasticity than the
      primary motor cortex in the adult monkey.

PMID- 15941623
TI  - Disposition of 3H-selamectin and 3H-ivermectin in the brain of the cat flea
      Ctenocephalides felis felis using micro-image analysis.
AB  - In addition to intrinsic potency and metabolic stability, the disposition of an
      antiparasitic drug within the target parasite plays a major role in determining
      drug activity. A novel technique that allows the disposition of radiolabelled
      drugs to be visualised within the body of the cat flea (Ctenocephalides felis
      felis) is described. The concentrations of two macrocyclic lactones, (3)H
      selamectin and (3)H-ivermectin, within the supra- and sub-oesophageal ganglia of
      the flea brain following in vitro feeding of fleas on different doses of drug
      solubilised in calf blood have been measured. Drug disposition was visualised in
      cryostat sections of fleas using a micro-image analysis (MIA). A relationship
      between the concentration of radioactivity in the ganglia and the dose of drug in
      the blood meal was obtained. The concentration of selamectin in the ganglia was
      significantly higher than ivermectin at all doses investigated. The enhanced
      concentration of selamectin, at a site rich in glutamate-gated chloride channels
      may, in part, explain the higher potency of selamectin against fleas compared to
      ivermectin.

PMID- 15941625
TI  - Development of an autotrophic culture system for the in vitro mycorrhization of
      potato plantlets.
AB  - An autotrophic culture system was developed for the in vitro mycorrhization of
      potato plantlets. Roots of micropropagated plantlets were associated to an
      arbuscular mycorrhizal fungus under in vitro conditions, while shoots developed
      under open air conditions. Several thousand spores, an extensive extraradical
      mycelium and an abundant root colonization were obtained. Spores were able to
      colonize new plantlets under the same conditions. These results support the
      capacity of the autotrophic culture system to continuously culture arbuscular
      mycorrhizal fungi and may serve as a powerful tool to investigate various aspects
      of the symbiosis for which a source-sink relationship and photosynthetic active
      tissues are necessary.

PMID- 15941626
TI  - Use of hydrolysates from Atlantic cod (Gadus morhua L.) viscera as a complex
      nitrogen source for lactic acid bacteria.
AB  - Hydrolysates of cod viscera were tested as an alternative to commonly used
      complex nitrogen sources (peptones and/or extracts) for the type strains of the
      lactic acid bacteria Lactococcus lactis, Lactobacillus acidophilus, Lactobacillus
      helveticus, Lactobacillus casei, Lactobacillus sakei and Pediococcus pentosaceus.
      Comparative studies with MRS-like media containing different nitrogen sources
      showed that all the fish hydrolysates performed equally well or better than
      commercial extracts/peptones for all selected lactic acid bacteria.

PMID- 15941624
TI  - Transstadial and intrastadial experimental transmission of Ehrlichia canis by
      male Rhipicephalus sanguineus.
AB  - The acquisition and transmission of rickettsial pathogens by different tick
      developmental stages has important epidemiological implications. The purpose of
      this study was to determine if male Rhipicephalus sanguineus can experimentally
      acquire and transmit Ehrlichia canis in the absence of female ticks. Two trials
      were performed where nymphal and male R. sanguineus were simultaneously
      acquisition fed on the same infected donor hosts, and transstadially or
      intrastadially exposed male ticks were fed on separate pathogen-free dogs as a
      test for transmission. A single-step p30-based PCR assay was used to test canine
      and tick hosts for E. canis infections before and after tick feeding. E. canis
      was detected after either intrastadial or transstadial passage in male ticks, the
      organism remained detectable in both tick groups after transmission feeding, and
      both tick groups transmitted the rickettsia to susceptible dogs. Infection of
      dogs via tick feeding resulted in milder clinical signs and lower antibody titers
      than intravenous inoculation of carrier blood, but further investigation is
      needed to understand the mechanisms responsible for this observation. These
      results demonstrate that male R. sanguineus can take multiple feedings, and that
      they can both acquire and transmit E. canis in the absence of female ticks. This
      tick development stage could be important in transmission of E. canis, and
      perhaps related pathogens, between vertebrate hosts under natural and
      experimental conditions.

PMID- 15941627
TI  - Immune responses of mice to vaccinia virus recombinants expressing either
      Listeria monocytogenes partial listeriolysin or Brucella abortus ribosomal L7/L12
      protein.
AB  - The Brucella abortus L7/L12 gene encoding ribosomal protein L7/L12 and the
      Listeria monocytogenes partial hly gene encoding the protective region of the
      hemolysin (partial listeriolysin, pLLO) were cloned into vaccinia virus by
      homologous recombination to produce recombinants WRL7/L12 and WRpLLO,
      respectively. The ability of these recombinants to induce humoral, cell mediated
      and protective immune response in mice was assessed. Although mice inoculated
      with WRL7/L12 recombinant produced antibodies specific to vaccinia virus and
      L7/L12 antigens, they were not protected against a virulent challenge with B.
      abortus 2308 strain. In contrast, mice inoculated with WRpLLO were protected
      against a challenge with virulent L. monocytogenes. Stimulation with purified
      fusion listeriolysin protein (MBP-LLO), but not with unrelated control protein
      (MBP), induced splenocytes from WRpLLO-inoculated mice to secrete significantly
      higher amounts of IFN-gamma than saline inoculated mice. Mice inoculated with
      either WRpLLO or WRL7/L12 recombinants produced predominantly IgG2a isotype
      antibody responses, indicative of a Th1 type of immune response. The protective
      potential of the WRpLLO recombinant correlated with the level of IFN-gamma
      produced in these mice.

PMID- 15941629
TI  - Significant IgG-immunoreactivity of the spermatogonia of the germ cell-depleted
      testis after busulfan treatment.
AB  - Busulfan kills spermatogonia with the exception of a few that are attached to the
      basal membrane of the seminiferous epithelium. In mice, these remaining
      spermatogonia reacted strongly to a goat anti-mouse IgG antibody. Spermatogonia
      in untreated testes rarely showed the same reactivity. Testicular IgG levels are
      normally minimal but increase markedly, 4 weeks after busulfan treatment before
      peaking at week 6. Laser scanning cytometry analysis of control and busulfan
      treated testicular cells showed busulfan treatment increased the frequency of
      cells that were positive for not only IgG (from 0.67+/-0.29 to 16.5+/-3.8%) but
      also for alpha6-integrin, beta1-integrin, GFR(-1 and/or Ret. Thus, an enrichment
      in putative male stem cells correlates with appearance of IgG expression.
      Confocal microscopy revealed busulfan-treated cells contained both IgG and
      GFRalpha-1, and that the initial surface IgG became intracellular in the weeks
      following busulfan treatment. The basement membranes of the seminiferous tubules
      were compromised by busulfan treatment as the mRNA expression profiles of various
      adhesion molecules in the basement membranes were altered and electron microscopy
      revealed severe damage. Serum IgG levels increased in a manner corresponding with
      the increase in testicular IgG levels. Thus, it appears that in the busulfan
      treated testis, small breaches of the blood-testis barrier leak IgG that is then
      taken up by a significant number of spermatogonia. When the busulfan-resistant
      germ cells were transferred into recipient germ cell-depleted testes, they
      settled and repopulated the recipient testes. Thus, the IgG-bearing cells
      observed after busulfan treatment may be putative spermatogonial stem cells.

PMID- 15941628
TI  - Influence of different doses of progesterone treatments on ovarian follicle
      status in beef cows.
AB  - To determine a dose of progesterone (P4) that allow ovarian follicular wave
      control, Aberdeen Angus cows were randomly assigned into four groups: T600 (n=5),
      600 mg of P4/day; T400 (n=5), 400 mg of P4/day; T200 (n=4), 200mg of P4/day and
      Control (n=4) (excipient only). Progesterone was injected from day 3 to 9 of
      estrous cycle. Ultrasonographies and blood sample collections were performed
      daily from day 2 to 10 and on day 15 of the estrous cycle. Additionally, an
      ultrasonographic study was conducted on day 13. Progesterone concentrations were
      different among all groups (P<0.01). The diameter of the dominant follicle was
      greater for control than for T200, T400 and T600 groups (P<0.01); there was no
      difference between T200 and T400 (P>0.05), but they had a greater diameter
      follicle than the T600 group (P<0.01). The growth rate of the dominant follicle
      between day 3 and 7 of estrous cycle was greater for control group (1.63+/-0.3
      mmday(-1)) than for T200 (0.56+/-0.19 mmday(-1), P<0.05), T400 (0.6+/-0.23 mmday(
      1), P<0.05) and T600 (0.11+/-0.13 mmday(-1), P<0.01) groups. The mean number of
      class I follicles (3-4mm) per day for the entire experimental period was less for
      the control group than for T200 (P<0.05), T400 and T600 (P<0.01) groups (3.7+/
      1.3; 5.3+/-1.3; 6.6+/-1.8 and 8.1+/-1.9, respectively). The mean number for the
      T200 group was less than for T600 (P<0.05) and similar for T400 and T600 groups
      (P>0.05). The number of class III follicles was greater for control group than
      for the other groups (P<0.01). T200 and T400 groups had similar numbers of class
      III follicles (P>0.05) and both had greater numbers of follicles than the T600
      group (P<0.05). The diameter of the corpus luteum of the T600 group (15.8+/-1.6
      mm) was less than for control (21.0+/-2.5 mm, P<0.01), T200 (19.3+/-2.7 mm,
      P<0.01) and T400 (20.0+/-2.2 mm) groups (P<0.05). The mean diameter of corpus
      luteum of T200 was similar to T400 (P>0.05), but different from the control group
      (P<0.05). In conclusion, the daily intramuscular administration of 200mg or more
      of progesterone from day 3 to 9 of the estrous cycle indicates that plasma
      concentrations of progesterone can be used to modify the pattern of follicular
      development during the follicular wave. From day 5 of the estrous cycle,
      progesterone concentrations greater than 15 ng/ml (T600 group: 600 mg/day of
      progesterone from day 3 to 9 of the estrous cycle) inhibit dominant follicle
      development, increase the class I follicle populations (3-4 mm) and diminish the
      development of the corpus luteum.

PMID- 15941630
TI  - Evaluation of mammographic density and (99m)Tc-sestamibi scintimammographic
      uptake in postmenopausal women on hormone replacement therapy.
AB  - OBJECTIVE: To evaluate changes in mammographic density and (99m)Tc-sestamibi
      scintimammographic uptake in postmenopausal women on hormone replacement therapy
      (HRT). METHODS: Seventy-five postmenopausal women were prospectively studied and
      allocated into three groups: 50 women were randomized to either Group 1 (G1,
      n=25), which received 2mg of 17beta-oestradiol continuously combined with 1mg of
      norethisterone acetate (E2/NETA, Kliogest, Medley) or Group 2 (G2), which
      received 2.5mg/day of tibolone (Livial, Organon). The remaining 25 women, who
      were asymptomatic and had no desire to undergo HRT, constituted the control group
      (G3). Each patient was submitted to both mammography and scintimammography at
      baseline and after six months. Mammographic density was evaluated by using the BI
      RADS classification system. The classification system of Barros et al. was used
      in the interpretation of scintimammography. For statistical analysis, the Chi
      square test, ANOVA and Pearson's correlation were used. RESULTS: At six months,
      increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3
      patients (p<0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and
      24% in G3 (p<0.001). Increases in both density and uptake were significantly
      higher in the group on E2/NETA than among tibolone users and the controls.
      CONCLUSION: In postmenopausal women, HRT with E2/NETA was associated with
      increased mammographic density and increased (99m)Tc-sestamibi scintimammographic
      uptakes, suggesting greater mithochondrial activity in the cells of the mammary
      duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that
      the effects on the breast were reduced. The same was observed in the control
      group.

PMID- 15941631
TI  - Physicochemical characterization of poly(L-lactic acid) and poly(D,L-lactide-co
      glycolide) nanoparticles with polyethylenimine as gene delivery carrier.
AB  - Polymer nanoparticles have been used as non-viral gene delivery systems and drug
      delivery systems. In this study, biodegradable poly(L-lactic acid)
      (PLA)/polyethylenimine (PEI) and poly(D,L-lactide-co-glycolide) (PLGA)/PEI
      nanoparticles were prepared and characterized as gene delivery systems. The
      PLA/PEI and PLGA/PEI nanoparticles, which were prepared by a diafiltration
      method, had spherical shapes and smooth surface characteristics. The size of
      nanoparticles was controlled by the amount of PEI, which acted as a hydrophilic
      moiety, which effectively reduced the interfacial energy between the particle
      surface and the aqueous media. The nanoparticles showed an excellent dispersive
      stability under storage in a phosphate-buffered saline solution for 12 days. The
      positive zeta-potentials for the nanoparticles decreased and changed to negative
      values with increasing plasmid DNA (pDNA) content. Agarose gel electrophoresis
      showed that the complex formation between the nanoparticles and the pDNA
      coincided with the zeta-potential results. The results of in vitro transfection
      and cell viability on HEK 293 cells indicated that the nanoparticles could be
      used as gene delivery carriers.

PMID- 15941632
TI  - Novel anhydrous emulsions: formulation as controlled release vehicles.
AB  - Novel anhydrous emulsions, which may offer some advantages as depot or reservoir
      vehicles for lipophilic drugs in controlled delivery systems, were formulated
      using castor oil as the disperse phase and dimethicone or cyclopentasiloxane as
      the continuous phase. Among the emulsifiers studied only silicone surfactants
      (cyclomethicone/dimethicone copolyols) which were miscible in silicone oil
      stabilized the emulsions. Cyclomethicone/PEG/PPG-18/18 Dimethicone and
      Cyclopentasiloxane/PEG/PPG-18/18 Dimethicone were more effective in lowering the
      interfacial tension between castor oil and both dimethicone and
      cyclopentasiloxane. Emulsions formulated using either of these two surfactants
      were found to be stable against phase separation and exhibited least globule
      growth over 168 h. The average particle size was found to be 2-6 microm in these
      systems formed by probe sonication. Slow release patterns of 3H
      dehydroepiandrosterone (DHEA) and 3H-dexamethasone solubilized in the disperse
      castor oil phase into an aqueous dialyzing medium were observed over 48 h.

PMID- 15941633
TI  - Strategies for cytosolic delivery of liposomal macromolecules.
AB  - Potential approaches to achieve cytosolic delivery of liposomal macromolecules
      are presented. These approaches include: (1) the co-encapsulation of fusogenic
      peptides into targeted drug-containing liposomes (2) coupling of the HIV-1
      derived cell-penetrating peptide TAT to the surface of liposomes and (3)
      photochemical internalization, based on photochemically inducible
      permeabilization of endocytic vesicles.

PMID- 15941634
TI  - Preparation and characterisation of liposomes encapsulating ketoprofen
      cyclodextrin complexes for transdermal drug delivery.
AB  - Multilamellar vesicle (MLV) liposomes containing ketoprofen-cyclodextrin
      complexes intended for drug topical delivery were prepared, with the aim of
      simultaneously exploiting the favourable properties of both carriers. Drug
      complexes with beta-cyclodextrin (betaCyd) and hydroxypropyl-betaCyd (HPbetaCyd),
      prepared by coevaporation and sealed-heating methods, were characterised by
      differential scanning calorimetry, hot stage microscopy, scanning electron
      microscopy and tested for dissolution properties. The coevaporated system with
      HPbetaCyd was the most effective, enabling an about 11-fold increase in drug
      dissolution. Drug and drug-Cyd systems were incorporated in MLV liposomes
      prepared by the thin layer evaporation technique. All liposomal formulations were
      characterised for encapsulation efficiency, particle size and morphology, using
      dialysis, light scattering and transmission electron microscopy techniques,
      respectively. MLV formation was negatively influenced by the presence of Cyd;
      nevertheless, it was possible to prepare stable MLVs containing ketoprofen-Cyd
      complexes. The presence of the Cyd complex affected MLV dimensions but not their
      lamellar structure. The complex with HPbetaCyd, in virtue of its greater
      stability than the betaCyd one, allowed higher percentages of encapsulation and
      gave rise to more stable MLV systems. Permeability studies of drug and drug-Cyd
      complexes, as such or incorporated in liposomes, performed both across artificial
      membranes and rat skin, highlighted a favourable effect of Cyd on drug permeation
      rate, due to its solubilizing action; by contrast, unexpectedly, no skin
      permeation enhancer property of liposomes has been evidenced. Confocal laser
      scanning microscopy studies carried out with the rhodamine-Cyd complex as
      fluorescent marker, confirmed such results, showing that the label permeated
      deeper across rat skin layers when it was in solution than when entrapped in
      liposomes.

PMID- 15941635
TI  - Antioxidant activity and antiproliferative action of methanolic extract of Geum
      quellyon Sweet roots in human tumor cell lines.
AB  - Geum quellyon Sweet, a perennial herb of the Rosaceae family, has been used in
      the traditional medicine of the Mapuche Amerindians of Chile to treat tooth
      neuralgia, gastric inflammation, prostatitis and to regulate menstruation, and
      for its diuretic and aphrodisiac properties. Although many benefits have been
      claimed for this plant, few scientific studies are available in the literature.
      In this study, we investigated the antioxidant activity of a methanolic extract
      of Geum quellyon roots. We also examined the anticancer action of this plant on
      Caco-2 (colon adenocarcinoma cells), DU-145 (androgen-insensitive prostate cancer
      cells) and KB (oral squamous carcinoma cells) human tumor cell lines. Our data
      showed that Geum quellyon extract, containing tannins, exhibits interesting
      antioxidant properties, expressed by its capacity to scavenge 1,1-diphenyl-2
      picryl-hydrazyl radical (DPPH) and superoxide anion (O(2)*-), to inhibit xanthine
      oxidase activity, to chelate metals, and to protect plasmid DNA from cleavage
      induced by hydroxyl radicals (*OH) and nitric oxide (NO). These results may
      explain, at least in part, its use in Mapuche traditional medicine for gastric
      inflammation and prostatitis. The assays on human tumor cell lines demonstrated
      that this natural product exhibits a inhibitory effect on all human cancer cells
      examined, and seem to indicate that necrosis cell death is triggered in KB cells
      and Caco-2, while apoptotic cell demise appears to be induced in DU-145. The
      effect evidenced in Caco-2 cells can be in part correlated to a modulation of
      redox-sensitive mechanisms.

PMID- 15941636
TI  - Inhibition of human endothelial cell proliferation by Gami--Jeonggi--San (Jiawei-
      Zhenqi--San) is accompanied by transcriptional up-regulation of p53 and Waf1
      tumor suppressor genes.
AB  - The effects of Gami-Jeonggi-San (GJS) on proliferation of human endothelial cell
      (HUV-EC-C) were investigated using a flow cytometry and a quantitative RT-PCR
      analysis of gene expression. An accumulation of cells at G(1) phase of the cell
      cycle was found at 72 h after treatment (10 microl/ml) while no detectable
      reduction of PCNA expression was recognized. To elucidate that the cell cycle
      inhibitory effect of GJS stems from its capability of transcriptional regulation
      of the cell cycle-controlling genes, we investigated mRNA expression of p53,
      Waf1, PCNA, Cyclin D1, Cdc2, Histone H3, c-Myc, and c-Fos. Significantly elevated
      mRNA levels of the p53 tumor suppressor gene and its down-stream mediator gene,
      Waf1, whose increased expressions were known to trigger G(1) cell cycle arrest,
      were observed. In contrast, a marked reduction of two early G(1)-specific, cell
      cycle stimulating genes, c-Myc and c-Fos, were found at 24h after treatment,
      while there were no detectable changes in expressions of G(1)-S or G(2)-M
      transition-related genes, indicating the G(1) specificity of GJS effect on the
      cell cycle. These results suggest that the pharmacological effects of GJS might
      be derived in part from inhibition of cellular proliferation of human endothelial
      cells, and that GJS inhibition of the cell cycle might stem from its regulatory
      capability on the transcription of the cell cycle-controlling genes, including
      p53 and Waf1 tumor suppressor genes.

PMID- 15941637
TI  - In vitro immunomodulatory effect of Pouteria cambodiana (Pierre ex Dubard) Baehni
      extract.
AB  - The methanolic stem bark extract from Pouteria cambodiana (Pierre ex Dubard)
      Baehni was evaluated for immunomodulating activity on BALB/c mice. The
      antioxidant effect was also assessed. The extract presented a good dose-response
      effect in the peritoneal macrophage phagocytosis assay with higher activity at
      1mg/ml and an EC50 of 0.02 mg/ml and also activated lysosomal enzyme activity
      with an EC50 of 0.16 mg/ml. In the splenocyte proliferation assay, the extract
      without mitogen was active (EC50, 0.01 mg/ml) while the EC50 of the extract with
      lipopolysaccharide (LPS) and pokeweed mitogen (PWM) were 0.02 and 0.41 mg/ml,
      respectively. The extract showed low free radical scavenging activity in the 1,1
      diphenyl-2-picrylhydrazyl (DPPH) radical assay with an IC50 of 0.24 mg/ml, being
      less active than ascorbic acid, butylated hydroxytoluene (BHT) and alpha
      tocopherol which showed IC50 of 0.08, 0.10 and 0.11 mg/ml, respectively. The
      extract at doses up to 0.073 mg/ml had no effect on lipid peroxidation. The
      potent immunological but no antioxidant activity of the extract presented in this
      study can explain, at least in part, the Thai folklore application of this plant
      in the treatment of fever and skin eruption.

PMID- 15941638
TI  - Inhibitory effect on proliferation of vascular smooth muscle cells and protective
      effect on CCl(4)-induced hepatic damage of HEAI extract.
AB  - The effects of methanol extract from Hericium erinaceus cultivated with Artemisia
      iwayomogi (HEAI) on proliferation of vascular smooth muscle cells and CCl(4)
      induced hepatic damage were evaluated. HEAI was shown to have a potent inhibitory
      effect on the proliferation of vascular smooth muscle cells (VSMCs).
      Interestingly, a methanol extract of Hericium erinaceus showed no inhibitory
      effect on the proliferation of VSMCs, while a methanol extract of Artemisia
      iwayomogi possessed strong inhibitory effects on the proliferation of VSMCs.
      Therefore, the inhibitory effects of HEAI may be caused by the changes of
      chemical components in the culture broth after the addition of Artemisia
      iwayomogi in the HEAI growth media. HEAI also had a strong protective effect on
      CCl(4)-induced hepatic damage in rats. The activity was evaluated using
      biochemical parameters such as glutamic oxalacetic transaminase (GOT), glutamic
      pyruvic transaminase (GPT) and alkaline phosphatase (ALP). HEAI treatment caused
      a significant reduction in the activity of GOT but not of GPT and ALP in
      comparison with CCl(4) treatment alone. Histopathological studies showed that
      liver samples treated with HEAI were significantly different when compared to non
      treated animals after CCl(4) exposure.

PMID- 15941639
TI  - Fatal methadone intoxication in an infant.
AB  - Presented are the case history and toxicological findings of an infant fatality
      involving methadone. A mother found her 10-month-old infant unresponsive in a
      crib. The infant was taken to a hospital; however, she was cold and stiff on
      arrival and was pronounced dead. Few details regarding the case history were
      known at the time, and the autopsy findings were unremarkable. Specimens were
      submitted for a full toxicological analysis, including an alcohol analysis by
      headspace gas chromatography with flame ionization detection; a screen for drugs
      of abuse and several prescription drug classes using an enzyme-linked
      immunosorbent assay technique (ELISA); and a screen for basic compounds using gas
      chromatography-mass spectrometry (GC-MS). Positive findings were confirmed and
      quantitated using GC-MS. Methadone was detected in subclavian blood at a
      concentration of 0.67 mg/L. The cause of death was determined to be "methadone
      intoxication", and the manner of death was "homicide". A discussion of the case
      circumstances, the toxicology findings and methadone pharmacokinetics are
      presented.

PMID- 15941640
TI  - Pigmented villonodular synovitis of the temporomandibular joint: differential
      diagnosis of the parotid mass.
AB  - Pigmented villonodular synovitis (PVNS) is a benign, locally invasive lesion of
      the synovium of joints, bursae, and tendon sheaths. Its occurrence in the
      temporomandibular joint is very rare. We report two cases of PVNS involving
      temporomandibular joint (TMJ), not only for its unusual location but also to
      underscore how its clinical presentation can mimic a parotid mass. Treatment
      requires total TMJ synovectomy whereas multiple recurrences or aggressive
      clinical behavior may require postoperative radiation therapy following complete
      surgical extirpation.

PMID- 15941641
TI  - A validated chiral LC method for the enantiomeric separation of Zolmitriptan key
      intermediate, ZTR-5.
AB  - A new and accurate chiral liquid chromatographic method was described for the
      enantiomeric separation of ZTR-5 [(4S)-4-(4-aminobenzyl)-2-oxazolidinone, (S)
      isomer], a key intermediate of Zolmitriptan in bulk drugs. The enantiomers of ZTR
      5 were baseline resolved on a Chiralpak AD-H (250 mm x 4.6 mm, 5 microm) column
      using a mobile phase system containing hexane:ethanol (70:30, v/v). The
      resolution between the enantiomers was not less than four and interestingly
      distomer was eluted prior to eutomer. The limit of detection and limit of
      quantification of (4R)-4-(4-aminobenzyl)-2-oxazolidinone [(R)-isomer] were found
      to be 250 and 750 ng/ml, respectively, for 10 microl injection volume. The
      percentage recovery of (R)-isomer ranged from 92.0 to 105.6 in the bulk drug
      samples of ZTR-5. The validated method yielded good results regarding precision,
      linearity, accuracy and ruggedness. The proposed method was found to be suitable
      and accurate for the quantitative determination of (R)-isomer in bulk drug
      samples of ZTR-5.

PMID- 15941642
TI  - Determination of omeprazole in human plasma by liquid chromatography-electrospray
      quadrupole linear ion trap mass spectrometry.
AB  - An analytical method for the determination of omeprazole in human plasma has been
      developed based on liquid chromatography mass spectrometry. The analyte and
      internal standard sildenafil are extracted from plasma by liquid-liquid
      extraction using diethyl ether:dichloromethane (60:40, v/v) and separated by
      reversed phase high-performance liquid chromatography (HPLC) using
      acetonitrile:methanol:10 mM ammonium acetate (37.5:37.5:25, v/v/v) as mobile
      phase. Detection is carried out by multiple reaction monitoring on a Q TRAP
      LC/MS/MS system (Q TRAP). The method has a chromatographic run time of 3.5 min
      and is linear within the range 0.50-800 ng/mL. Intra- and inter-day precision
      expressed as relative standard deviation ranged from 0.4 to 8.5% and from 1.2 to
      6.8%, respectively. Assay expressed as relative error was <5.7%. The method has
      been applied in a bioequivalence study of two capsule formulations of omeprazole.

PMID- 15941643
TI  - Stability-indicating HPTLC determination of curcumin in bulk drug and
      pharmaceutical formulations.
AB  - A simple, selective, precise and stability-indicating high-performance thin-layer
      chromatographic method of analysis of curcumin both as a bulk drug and in
      formulations was developed and validated. The method employed TLC aluminium
      plates precoated with silica gel 60 F-254 as the stationary phase. The solvent
      system consisted of chloroform:methanol (9.25:0.75 v/v). This system was found to
      give compact spots for curcumin (R(f) value of 0.48 +/- 0.02). Densitometric
      analysis of curcumin was carried out in the absorbance mode at 430 nm. The linear
      regression analysis data for the calibration plots showed good linear
      relationship with r = 0.996 and 0.994 with respect to peak height and peak area,
      respectively, in the concentration range 50-300 ng per spot. The mean value +/-
      S.D. of slope and intercept were 1.08 +/- 0.01, 51.93 +/- 0.54 and 8.39 +/- 0.21,
      311.55 +/ -3.23 with respect to peak height and area, respectively. The method
      was validated for precision, recovery and robustness. The limits of detection and
      quantitation were 8 and 25 ng per spot, respectively. Curcumin was subjected to
      acid and alkali hydrolysis, oxidation and photodegradation. The drug undergoes
      degradation under acidic, basic, light and oxidation conditions. This indicates
      that the drug is susceptible to acid, base hydrolysis, oxidation and photo
      oxidation. Statistical analysis proves that the method is repeatable, selective
      and accurate for the estimation of said drug. As the method could effectively
      separate the drug from its degradation product, it can be employed as a stability
      indicating one.

PMID- 15941644
TI  - Potential role of leptin in increase of fatty acid synthase gene expression in
      chicken liver.
AB  - Leptin is reported to have direct effects on lipogenesis in peripheral tissues
      that are independent of its central effects on food intake and body weight. These
      experiments have been mainly carried out in rodents (different models of obesity)
      in which lipogenesis occurs in both adipose tissue and liver. Such effects are
      unknown in birds in which lipogenesis occurs essentially in the liver. In this
      study, leptin gene expression and circulating leptin levels were examined in two
      chicken lines, selected for high (FL) or low (LL) abdominal fat pad size, at
      different nutritional states (fasted and fed state). In addition, effects of
      recombinant chicken leptin on liver metabolism were investigated. Hepatic leptin
      and fatty acid synthase (FAS) gene expression and plasma leptin levels were
      significantly higher in FL than in LL chickens (P < 0.05). In both lines, fasting
      significantly reduced hepatic leptin and FAS mRNA levels (P < 0.05). Continuous
      administration of recombinant chicken leptin (8 microg/kg/h) during 6 h
      significantly inhibited food intake (51%) and increased leptinemia (23-fold)
      compared to untreated group. Despite the decrease of food intake, leptin
      significantly induced the expression of FAS in chicken liver. These changes were
      accompanied by a significant down-regulation of leptin receptor gene expression,
      however SREBP-1, the main transcription factor of lipogenic genes, remained
      unchanged. This result suggests a local potential role of leptin in the
      regulation of avian hepatic lipogenesis, and explain, at least partly, the
      metabolic changes evolved during the divergent selection of FL and LL chickens.

PMID- 15941645
TI  - Cytokine expression in an ex vivo culture system of duodenal samples from dogs
      with chronic enteropathies: modulation by probiotic bacteria.
AB  - There is evidence that probiotics have immune-modulating effects on intestinal
      inflammation during chronic enteropathies (CE). In an ex vivo culture system we
      investigated the influence of probiotics on mRNA and protein expression levels of
      cytokines in intestinal samples from dogs suffering from CE. Duodenal samples of
      client-owned dogs with CE (group CE; n = 12) were collected during diagnostic
      endoscopy. Additional duodenal samples of gastrointestinally healthy dogs (group
      C; n = 4) from an unrelated study were available. Based on histopathological
      analyses, no pathological changes or only mild to moderate eosinophilic and/or
      lymphoplasmacytic duodenitis were diagnosed. Tissue samples were cultured: (1)
      with cell culture medium alone (negative control), (2) with a probiotic cocktail
      (PC), constituted of three Lactobacilli spp. from healthy canine fecal isolates,
      (3) with the individual strains of PC, and (4) with a placebo powder. Viability
      of intestinal tissue and probiotic bacteria before and after culture was
      evaluated. The mRNA abundance of interleukin (IL)-10, IL-12p40, interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, and transforming growth factor (TGF)
      beta1 was analyzed by real-time polymerase chain reaction (RT-PCR). Protein
      concentrations of IFN-gamma and IL-10 were measured in culture supernatant by
      ELISA. Results of RT-PCR were expressed as 2(-2DeltaCrossing Point) x 100 after
      normalization with beta-actin. There was a loss of about 1 log CFU/mL of
      probiotic bacteria during the incubation period. Viability of tissue was
      maintained as confirmed by non-significant release of lactate dehydrogenase. In
      C, addition of PC increased IL-10 mRNA levels (P < 0.1). In CE, PC increased mRNA
      and protein levels of IL-10 (P < 0.05). On the mRNA level, the ratio of TNFalpha
      /IL-10, IFN-gamma/IL-10, and IL-12p40/IL-10 decreased after addition of PC (P <
      0.05). The results demonstrate favorable effects of PC on regulatory cytokines
      relative to inflammatory cytokines that might contribute to reduction of
      intestinal inflammation.

PMID- 15941646
TI  - Subcortical hyperintensities impact cognitive function among a select subset of
      healthy elderly.
AB  - Previous studies have examined the impact of subcortical hyperintensities (SH), a
      proxy measure of cerebrovascular disease, on the cognitive abilities of otherwise
      healthy older adults. However, there remains a limited understanding as to what
      extent this MRI marker of pathological processes explains the decline in specific
      cognitive functions that occur nearly ubiquitously with advanced age, especially
      in relation to other age-related imaging markers. In the present study we
      compared cognitive abilities between a sample of 53 older healthy adults (age
      range=50-79) and a sample of 53 younger adults (age range=21-40). As expected,
      the older group performed significantly worse on most cognitive measures compared
      to the younger group. Frontal volume and total grey matter volume were also
      significantly reduced among the older individuals compared to the younger
      individuals. SH volume was consistently associated with cognitive function in
      older adults, though, this relationship was evident only for a relatively small
      subset of older individuals with the most severe SH. These data suggest that the
      relationship between SH and cognition in the elderly is driven by a subset of
      individuals who may be in the earliest stages of vascular cognitive impairment.
      Further, the findings suggest that cognitive aging is largely determined by
      factors other than SH for most older adults.

PMID- 15941647
TI  - Are sperm parameters the best indicator of 2,5-hexanedione reproductive toxicity
      in male rats?
AB  - In this study on 40 male Wistar rats of approximately 3-weeks-old, the effects of
      2,5-hexanedione on sperm principal parameters were examined by subcutaneously
      administering 100, 200 and 400 mg/(kgday) for 12 weeks. Other indicators of 2,5
      hexanedione intoxication were examined: testes, epididymides, body weight, limb
      paralysis and histology. The sperm motility was adversely affected in all of the
      three treatment groups. No sperm motility at all was observed in the 200 and 400
      mg/(kgday) treatment groups and rapid progressive motility was significantly
      reduced in the 100 mg/(kgday) group (P<0.05). The sperm concentration and
      morphology, testes, epididymides and body weight were significantly affected in
      the 200 and 400 mg/(kgday) groups but not in the 100 mg/(kgday) group (P<0.05).
      All the rats in the 400 mg/(kgday) group could not move due to leg paralysis,
      whereas only 50% of the rats in the 200mg/(kgday) group and none in the 100
      mg/(kgday) were affected. Histological examination of the testes in the 400, 200
      and 100 mg/(kgday) groups revealed Sertoli cell-only syndrome in 70, 30 and 0% of
      the rats, respectively. In conclusion, this study has shown that sperm motility
      was the most significantly sensitive indicator of 2,5-hexanedione intoxication in
      all the treatment groups.

PMID- 15941648
TI  - Vowel effect on glottal parameters and the magnitude of jaw opening.
AB  - This study investigated the relationship among the magnitude of jaw opening,
      intrinsic fundamental frequency (F0), and glottal parameters in natural speech.
      Acoustic, jaw opening, and electroglottographic (EGG) signals were simultaneously
      recorded. The subjects were 10 healthy men with New Zealand English as their
      native language. Subjects were asked to repeat a standard nonemphasized sentence
      in which one of the target vowels (/a/, /e/, /i/, /o/, and /u/) was embedded in
      various contexts. The glottal parameters F0, open quotient (OQ), and speed
      quotient (SQ) were measured from the EGG signal. Results of a series of one-way
      repeated-measures analyses of variance (ANOVA) showed a significant vowel effect
      on the magnitude of jaw opening [F(4, 24) = 25.512, P < .001], F0 [F(4, 28) =
      45.415, P < .001] and speed quotient [F(4, 28) = 5.233, P = .003], but not on the
      open quotient [F(4, 28) = 0.501, P = .735]. The magnitude of jaw opening was
      found to be inversely related with F0 (r = -0.624, n = 25, P = .0009). These
      findings showed that the magnitude of jaw opening was related to F0 and that jaw
      opening might be a control signal for simulation of long-term F0 variation to
      achieve a higher degree of naturalness in artificial voice.

PMID- 15941649
TI  - Ophthalmologic and neurologic findings in two children exposed to vigabatrin in
      utero.
AB  - Vigabatrin (VGB) is an important treatment option for infantile spasms.
      Vigabatrin-induced visual field defects are at present the most important safety
      issue in the use of the drug. The knowledge concerning VGB-associated visual
      dysfunction in pediatric patients, particularly in those who have been exposed to
      VGB in utero is limited. We explored ophthalmic and neurologic findings in two
      children who have been exposed prenatally to VGB.

PMID- 15941650
TI  - Benign childhood epilepsy with occipital paroxysms: neuropsychological findings.
AB  - Benign childhood epilepsy with occipital paroxysms is classified among childhood
      benign partial epilepsies. The absence of neurological and neuropsychological
      deficits has long been considered as a prerequisite for a diagnosis of benign
      childhood partial epilepsy. Much evidence has been reported in literature in the
      latest years suggesting a neuropsychological impairment in this type of epilepsy,
      particularly in the type with Rolandic paroxysms. The present work examines the
      neuropsychological profiles of a sample of subjects affected by the early-onset
      benign childhood occipital seizures (EBOS) described by Panayotopulos. The
      patient group included 22 children (14 males and 8 females; mean age 10.1+/-3.3
      years) diagnosed as having EBOS. The patients were examined with a set of tests
      investigating neuropsychological functions: memory, attention, perceptive, motor,
      linguistic and academic (reading, writing, arithmetic) abilities. The same
      instruments have been given to a homogeneous control group as regards sex, age,
      level of education and socio-economic background. None of the subjects affected
      by EBOS showed intellectual deficit (mean IQ in Wechsler Full Scale 91.7; S.D.
      8.9). Results show a widespread cognitive dysfunction in the context of a focal
      epileptogenic process in EBOS. In particular, children with EBOS show a
      significant occurrence of specific learning disabilities (SLD) and other subtle
      neuropsychological deficits. We found selective dysfunctions relating to
      perceptive-visual attentional ability (p<0.05), verbal and visual-spatial memory
      abilities (p<0.01), visual perception and visual-motor integration global
      abilities (p<0.01), manual dexterity tasks (p<0.05), some language tasks
      (p<0.05), reading and writing abilities (p<0.01) and arithmetic ability (p<0.01).
      The presence of cognitive dysfunctions in subjects with EBOS supports the
      hypothesis that epilepsy itself plays a role in the development of
      neuropsychological impairment. Supported by other studies that have documented
      subtle neuropsychological deficits in benign partial epilepsy, we stress the
      importance of reconsidering its supposed "cognitive benignity", particularly in
      occipital types.

PMID- 15941651
TI  - Seizures in children with primary brain tumors: incidence and long-term outcome.
AB  - PURPOSE: To estimate the incidence and long-term outcome of brain tumor related
      seizures in children and to identify risk factors for adverse seizure outcome.
      METHODS: Analysis of medical records of children treated for brain tumor and
      seizures in a single institution. Children were identified from hospital database
      and neurology clinic records. Seizure status was characterized for the 6 months
      prior to most recent follow-up. RESULTS: Median follow-up after first seizure of
      the 157 analyzed children was 3.3 years. Tumor location was supratentorial in 81%
      and posterior fossa in 19%. Initial anti-epileptic drugs were phenytoin (n=52),
      carbamazepine (n=38), phenobarbital (n=14), gabapentin (n=31), or others (n=22).
      Seizures were controlled in 65% of the children and uncontrolled in 35% (17%
      intractable). Gabapentin showed a trend toward better seizure control (p=0.06).
      Neurologic deficit, T2 peri-cavity hyperintensity, and EEG slow waves were
      independently predictive of uncontrolled seizures by multivariate analysis.
      CONCLUSIONS: T2 peri-cavity hyperintensity, focal neurologic deficits, and EEG
      slow waves predict poor seizure control in children with brain tumors. Seizures
      can be controlled in most patients with brain tumors. Gabapentin use as first
      anti-epileptic drug needs to be studied prospectively.

PMID- 15941652
TI  - Cationic PLA nanoparticles for DNA delivery: comparison of three surface
      polycations for DNA binding, protection and transfection properties.
AB  - Biodegradable cationic nanoparticles (cNP) made of poly(lactide) (PLA) have been
      shown to be promising carrier systems for in vivo DNA delivery and immunization.
      In previous work, we have described a versatile approach for the elaboration of
      cationic PLA cNP based on the use of pre-formed particles and subsequent
      adsorption of a model polycation, the poly(ethylenimine) (PEI). Here, we
      evaluated two more polycations, chitosan and poly(2-dimethyl-amino)ethyl
      methacrylate (pDMAEMA)) to determine the most suitable one for the development of
      PLA cNP as DNA carriers. Cationic PLA-PEI, PLA-chitosan and PLA-pDMAEMA
      nanoparticles were compared for interaction with plasmid DNA and, more
      importantly, with regards to the biological properties of bound DNA. pDMAEMA
      coating yielded the most positively charged nanoparticles with the highest DNA
      binding capacity (32 mg/g). Loaded with DNA, all three cNP were in the same size
      range ( approximately 500 nm) and had a negative zeta potential (-50 mV). PLA
      chitosan was the only cNP that released DNA at pH 7; the two others required
      higher pH. Adsorption and release from cNP did not alter structural and
      functional integrity of plasmid DNA. Moreover, DNA coated onto cNP was partially
      protected from nuclease degradation, although this protection was less efficient
      for PLA-chitosan than others. The highest transfection efficiency in cell culture
      was obtained with PLA-pDMAEMA carriers. We have shown that at least three
      different cationic polymers (chitosan, PEI, pDMAEMA) can be used for the
      production of PLA-based particulate DNA carriers and most probably other cationic
      polymers can also be used in the same purpose. PLA-pDMAEMA cNP were the most
      promising system for DNA delivery in this in vitro study. Our future work will
      focus on the in vivo evaluation of these gene delivery systems.

PMID- 15941653
TI  - The aggregation behavior of O-carboxymethylchitosan in dilute aqueous solution.
AB  - O-Carboxymethylchitosan (OCMCS) is a kind of biocompatible derivatives of
      chitosan whose water solubility is strongly dependent on the degree of
      carboxymethylation. The OCMCS with 100 carboxymethyl groups and 75 amino groups
      per 100 anhydroglucosamine units of OCMCS was synthesized by the reaction of
      chitosan and monochloroacetic. When OCMCS was dissolved in water, its solution
      was neutral and OCMCS behaved like a weak polyanionic polyeclectrolyte because
      most of carboxylic groups were not dissociated in neutral aqueous solution. The
      aggregation behavior of OCMCS in aqueous solution was studied by surface
      tensiometry, steady-state fluorescence spectroscopy and viscometry. The critical
      aggregation concentration (cac) of OCMCS was determined to be between 0.042 mg/ml
      and 0.050 mg/ml. The possible aggregation mechanism of OCMCS in water was
      elucidated.

PMID- 15941654
TI  - Biodistribution of 68Ga-labelled phosphodiester, phosphorothioate, and 2'-O
      methyl phosphodiester oligonucleotides in normal rats.
AB  - Antisense oligonucleotides may hybridise with high selectivity to mRNA sequences
      allowing monitoring of gene expression or inhibition of the manifestation of
      altered genes inducing diseases. As part of the development of positron emission
      tomography methods, 17-mer antisense phosphodiester (PO), phosphorothioate (PS)
      and 2'-O-methyl phosphodiester (OMe) oligonucleotides specific for point
      mutationally activated human K-ras oncogene were labelled with 68Ga radionuclide
      via a chelator coupled to the probe. Hybridisation in solution and non-denaturing
      polyacrylamide gel electrophoresis (PAGE) with a subsequent exposure of the gels
      was performed to verify the hybridisation ability after labelling. The
      biodistribution was studied in male Sprague-Dawley rats by injecting 2MBq of 68Ga
      oligonucleotides via the tail vein and measuring the organ radioactivity
      concentration after 20, 60 and 120 min or using whole-body autoradiography with
      10 MBq 68Ga-oligonucleotide and 20 min incubation time. Control experiments were
      performed with 68GaCl3 and 68Ga-chelator complex. The results revealed that 68Ga
      labelling did not change the hybridisation abilities of the oligonucleotides. The
      biodistribution pattern depended on the nature of the oligonucleotide backbone.
      Bone marrow, kidney, liver, spleen and urinary bladder were the five organs of
      highest uptake with each oligonucleotide. The PO accumulated highly in the liver,
      whereas high kidney uptake dominated the PS and OMe patterns. Intact PS and OMe
      were detected in plasma samples taken 20 and 60 min after injection. This study
      supplies a base for the further development of 68Ga-labelled oligonucleotides as
      pharmacokinetic tools and a potential future use for in vivo imaging of gene
      expression.

PMID- 15941656
TI  - Malignant mesothelioma in Hong Kong.
AB  - Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic
      study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by
      reviewing medical records. Mesothelioma patients were identified from the
      database of 12 out of 20 hospitals that would have admitted mesothelioma patients
      territory-wide. These 12 hospitals served 73% of the total hospital bed-years of
      the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual
      incidence was one per million, which was similar to the background incidence of
      one to two per million among Caucasians. Occupational history was available in 43
      subjects. Three quarters of mesothelioma patients with available occupational
      history had occupational asbestos exposure. Restricting analysis to 48 patients
      with accessible medical records and using 67 occupational asbestosis patients for
      comparison, the epidemiology of mesothelioma in Hong Kong shares similarities
      with the literature: mean age of 63 years upon diagnosis, mean latency of 46
      years, median survival of 9.5 months, male predominance, selective presentation
      among women, high prevalence among workers in ships and dockyards, predominantly
      epithelioid type, lower prevalence of asbestos bodies, and negative association
      with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and
      peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of
      mesothelioma in the 2010s if effective occupational asbestos control measures are
      not in place.

PMID- 15941655
TI  - The role of stearoyl-CoA desaturase in the control of metabolism.
AB  - Since obesity is becoming increasingly prevalent worldwide, much effort is being
      devoted to understanding its pathogenesis and treatment. In recent years, several
      candidate genes have been proposed as therapeutic targets. However, stearoyl-CoA
      desaturase 1 (SCD1) is of special significance, because it is the major gene
      target of leptin-a central mediator of energy homeostasis. There is evidence that
      SCD1 deficiency activates metabolic pathways that promote beta-oxidation and
      decrease lipogenesis in liver and skeletal muscles. One mechanism is via
      increased activation of AMP-activated protein kinase. SCD1 mutation results also
      in global changes in expression of genes involved in lipid metabolism. SCD1
      deficient mice have increased energy expenditure, reduced body adiposity, and are
      resistant to diet-induced obesity. In this review, we examine data from our
      laboratory and others suggesting that SCD1 is an important component in the
      regulation of body metabolism.

PMID- 15941657
TI  - We read with great interest the case report 'Eosinophilic pericardial effusion in
      Churg-Strauss syndrome' by Stollberger et al.

PMID- 15941658
TI  - A field test of functional status as performance of activities of daily living in
      COPD patients.
AB  - Patients with chronic obstructive pulmonary disease (COPD) frequently experience
      activity restrictions and discomfort during activities of daily living (ADL).
      Functional status refers to the capacity to perform ADL. Available tests only
      partly measure this domain. Our aim was therefore to establish an assessment tool
      for functional status in COPD, the Glittre ADL-test. This field test includes a
      standardised set of ADL-like activities: Walking stairs, carrying, lifting
      objects, bending down and rising from a seated position. The primary variable was
      time to complete the test (ADL-time). Validity was investigated in 57 COPD
      patients by correlating ADL-time to pulmonary function, 6-min walking distance
      (6MWD) and questionnaires addressing health-related quality of life.
      Responsiveness was investigated in another 40 patients comparing ADL-time before
      and after rehabilitation. Median ADL-time was 4.16 min (range 2.57-14.47).
      Spearman rho=0.93 for test-retest reliability. ADL-time correlated with forced
      expiratory volume in 1s (rho=-0.61), St. George's Respiratory Questionnaire
      activity subscore (rho=0.43), dyspnoea during ADL (rho=0.35) and hospitalisation
      rate (rho=0.35). Despite a close overall correlation with 6MWD (rho=-0.82),
      variability was substantial, particularly for the more disabled patients. ADL
      time improved significantly after rehabilitation. Glittre ADL-test yields
      information complementary to 6MWD. It is a valid and reliable measure of
      functional status, useful for assessment of individual patients and
      rehabilitation programs.

PMID- 15941659
TI  - Molecular cloning and protein expression of Duchenne muscular dystrophy gene
      products in porcine retina.
AB  - Due to the difference between rodent and human retinal circuitry, we characterize
      a new animal model of retinal perturbation in neurotransmission in Duchenne
      Muscular Dystrophy (DMD) patients. We investigated the expression and
      localization of dystrophin proteins and dystrophin associated proteins in porcine
      retina by reverse transcription polymerase chain reaction, Western blot analysis
      and immunohistochemistry. Homologues of human DMD gene products and alternative
      spliced isoforms of Dp71 were identified. We observed that dystrophins were
      expressed in the outer plexiform layer, around blood vessels and at the inner
      limiting membrane as previously described in human and mouse retinae. Moreover,
      by double immunostaining we showed that beta-dystroglycan co-localizes with
      dystrophin in the outer plexiform layer whereas alpha1-syntrophin labeling
      differs from that for dystrophins. Using confocal laser microscopy we observed
      that dystrophins labeling co-localizes with pre- and post-synaptic cell markers
      in the outer plexiform layer. We suggest that porcine retina constitutes a good
      model to study the role of dystrophins in retinal neurotransmission and should be
      used to investigate the physiological roles of dystrophins in signal
      transduction.

PMID- 15941660
TI  - Comparison of different techniques for detecting 17p12 duplication in CMT1A.
AB  - Charcot-Marie-Tooth type 1A is caused by a 1.5Mb DNA duplication in the 17p12
      chromosomal region encompassing the peripheral myelin protein 22 gene. In the
      present study, we compared the Real-Time PCR with the other methods currently
      used for the diagnosis of Charcot-Marie-Tooth. By using a combination of junction
      fragment PCR, analysis of microsatellite markers, and pulsed field gel
      electrophoresis, we identified 76 unrelated patients with 17p12 duplication. In
      these patients, junction fragment PCR detected 63% of cases of duplication, the
      microsatellite markers method revealed 74%, while the combined use of
      microsatellite markers and junction fragment PCR revealed 91% of cases of Charcot
      Marie-Tooth type 1A. Pulsed field gel electrophoresis detected 100% of the cases
      with duplication, even in presence of atypical 17p12 duplication. Real-Time PCR
      detected 100% of the cases with Charcot-Marie-Tooth type 1A and was comparable to
      pulsed field gel electrophoresis. However, in contrast to pulsed field gel
      electrophoresis, Real-Time PCR does not need fresh blood, minimizes diagnosis
      time and cost, and thus can be easily used for the molecular diagnosis of Charcot
      Marie-Tooth type 1A.

PMID- 15941661
TI  - TGF-beta1 codon 25 gene polymorphism is associated with cirrhosis in patients
      with hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron
      metabolism with variable penetrance. Only a minority of C282Y homozygotes develop
      clinical overt disease and cirrhosis. The phenotypic heterogeneity of HHC may be
      due to host genetic factors influencing fibrogenesis such as cytokine gene
      polymorphisms. In this respect, we investigated the impact of functional genetic
      polymorphisms of TGF-beta1 (codon 10 Leu/Pro, codon 25 Arg/Pro), TNF-alpha (-308
      G/A, -238 G/A) and angiotensinogen (-6 G/A) on the development of cirrhosis in
      HHC. One hundred and forty-nine (111 male, mean age: 51.0+/-12.9) C282Y
      homozygotes who underwent liver biopsy were studied. Genotyping was performed by
      RFLP analysis. TGF-beta1 codon 25 genotypes Arg/Pro and Pro/Pro were more common
      in patients with cirrhosis than in those without (23.6% vs. 7.4%, p = 0.005). In
      contrast, the distribution of TGF-beta1 codon 10, TNF-alpha and angiotensinogen
      genotypes was not different. Logistic regression analysis identified male sex,
      age, serum ferritin and TGF-beta1 codon 25 Arg/Pro and Pro/Pro as independent
      predictors for the presence of cirrhosis. The adjusted odds ratio for TGF-beta1
      codon 25 Arg/Pro and Pro/Pro was 2.8 (95% CI 1.4-5.7, p = 0.004). In conclusion,
      C282Y homozygotes carrying TGF-beta1 genotypes Arg/Pro and Pro/Pro are more
      likely to develop cirrhosis than those with genotype Arg/Arg.

PMID- 15941662
TI  - Intracrystalline proteins and calcium oxalate crystal degradation in MDCK II
      cells.
AB  - We assessed the effects of intracrystalline urinary proteins on the ability of
      Type II Madin-Darby canine kidney (MDCK-II) cells to bind and degrade calcium
      oxalate monohydrate (COM) crystals. Binding of [14C]-labelled inorganic crystals
      (iCOM), and COM crystals precipitated from centrifuged and filtered (CF) or
      ultrafiltered (UF) human urine was quantified by radioactive analysis. SDS-PAGE
      confirmed the presence of intracrystalline proteins > 10 kDa in CF crystals and
      their absence from UF crystals. Morphological effects were assessed qualitatively
      by field emission scanning electron microscopy. iCOM crystals bound rapidly and
      extensively and were resistant to degradation. Binding of CF crystals was weaker
      than UF crystals, and both had markedly less affinity than iCOM. CF and UF
      crystals were extensively degraded within 90 min, the effect being more
      pronounced with CF. These results support our hypothesis that intracrystalline
      proteins protect against urolithiasis by facilitating intracellular proteolytic
      digestion and destruction of crystals phagocytosed by urothelial cells.

PMID- 15941663
TI  - Biochemical characterization and molecular evidence of a laccase from the bird's
      nest fungus Cyathus bulleri.
AB  - Cyathus bulleri, a bird's nest fungus, known to decolorize polymeric dye Poly R
      478, was found to produce 8 U ml(-1) of laccase in malt extract broth. Laccase
      activity appeared as a single band on non-denaturing gel. Laccase was purified to
      homogeneity by anion exchange chromatography and gel filtration. The enzyme was a
      monomer with an apparent molecular mass of 60 kD, pI of 3.7 and was stable in the
      pH range of 2-6 with an optimum pH of 5.2. The optimal reaction temperature was
      45 degrees C and the enzyme lost its activity above 70 degrees C. Enzyme could
      oxidize a broad range of various phenolic substrates. K(m) values for ABTS, 2,6
      dimethoxyphenol, guaiacol, and ferulic acid were found to be 48.6, 56, 22, and 14
      mM while K(cat) values were 204, 180, 95.6, and 5.2, respectively. It was
      completely inhibited by KCN, NaN(3), beta-mercaptoethanol, HgCl(2), and SDS,
      while EDTA had no effect on enzyme activity. The N-terminal amino acid sequence
      of C. bulleri laccase showed close homology to N-terminal sequences of laccase
      from other white-rot fungi. A 150 bp gene sequence encoding copper-binding
      domains I and II was most similar to the sequence encoding a laccase from
      Pycnoporus cinnabarinus with 74.8% level of similarity.

PMID- 15941664
TI  - Methylene spectral editing in solid-state 13C NMR by three-spin coherence
      selection.
AB  - A robust new solid-state nuclear magnetic resonance (NMR) method for selecting
      CH2 signals in magic-angle spinning (MAS) 13C NMR spectra is presented.
      Heteronuclear dipolar evolution for a duration of 0.043 ms, under MREV-8
      homonuclear proton decoupling, converts 13C magnetization of CH2 groups into two-
      and three-spin coherences. The CH2 selection in the SIJ (C H H) spin system is
      based on the three-spin coherence S(x)I(z)J(z), which is distinguished from 13C
      magnetization (S(x)) by a 1H 0 degrees/90 degrees pulse consisting of two 45
      degrees pulses. The two-spin coherences of the type S(y)I(z) are removed by a 13C
      90 degrees x-pulse. The three-spin coherence is reconverted into magnetization
      during the remainder of the rotation period, still under MREV-8 decoupling. The
      required elimination of 13C chemical-shift precession is achieved by a
      prefocusing 180 degrees pulse bracketed by two rotation periods. The selection of
      the desired three-spin coherence has an efficiency of 13% theoretically and of 8%
      experimentally relative to the standard CP/MAS spectrum. However, long-range
      couplings also produce some three-spin coherences of methine (CH) carbons.
      Therefore, the length of the 13C pulse flipping the two-spin coherences is
      increased by 12% to slightly invert the CH signals arising from two-spin
      coherences and thus cancel the signal from long-range three-spin coherences. The
      signal intensity in this cleaner spectrum is 6% relative to the regular CP/TOSS
      spectrum. The only residual signal is from methyl groups, which are suppressed at
      least sixfold relative to the CH2 peaks. The experiment is demonstrated on
      cholesteryl acetate and applied to two humic acids.

PMID- 15941665
TI  - The role of the arterial prestress in blood flow dynamics.
AB  - Blood flowing in a vessel is modelled using one-dimensional equations derived
      from the Navier-Stokes theory on the base of long pressure wavelength. The vessel
      wall is modelled as an initially highly prestressed elastic membrane, which
      slightly deforms under the blood pressure pulses. On the stressed configuration,
      the vessel wall undergoes, even in larger arteries, small deformation and its
      motion is linearized around such initial prestressed state. The mechanical fluid
      wall interaction is expressed by a set of four partial differential equations. To
      account for a global circulation features, the distributed model is coupled with
      a six compartments lumped parameter model which provide the proper boundary
      conditions by reproducing the correct waveforms entering into the vessel and
      avoid unphysical reflections. The solution has been computed numerically: the
      space derivatives are discretized by a finite difference method on a staggered
      grid and a Runge-Kutta scheme is used to advance the solution in time. Numerical
      experiments show the role of the initial stresses in the flow dynamics and the
      wall deformation.

PMID- 15941666
TI  - The quasi-static response of compliant prosthetic sockets for transtibial
      amputees using finite element methods.
AB  - The finite element method (FEM) is a very powerful tool for analyzing the
      behavior of structures, especially when the geometry and mechanics are too
      complex to be modeled with analytical methods. This study focuses on the analysis
      of patellar tendon bearing prosthetic sockets with integrated compliant features
      designed to relieve contact pressure between the residual limb and socket. We
      developed a FEM model composed of a socket, liner and residual limb and analyzed
      it under quasi-static loading conditions derived from experimentally measured
      ground reaction forces. The geometry of the residual limb, liner and socket were
      acquired from computed tomography (CT) data of a transtibial amputee. Three
      different compliant designs were analyzed using FEM to assess the structural
      integrity of the sockets and their ability to relieve local pressure at the
      fibula head during normal walking. The compliant features consisted of thin-wall
      sections and two variations of spiral slots integrated within the socket wall.
      One version of the spiral slots produced the largest pressure relief, with an
      average reduction in local interface pressure during single-leg stance (20-80% of
      the stance phase) from 172 to 66.4 kPa or 65.8% compared to a baseline socket
      with no compliant features. These results suggest that the integration of local
      compliant features is an effective method to reduce local contact pressure and
      improve the functional performance of prosthetic sockets.

PMID- 15941669
TI  - TA-clustering: cluster analysis of gene expression profiles through Temporal
      Abstractions.
AB  - This paper describes a new technique for clustering short time series of gene
      expression data. The technique is a generalization of the template-based
      clustering and is based on a qualitative representation of profiles which are
      labelled using trend Temporal Abstractions (TAs); clusters are then dynamically
      identified on the basis of this qualitative representation. Clustering is
      performed in an efficient way at three different levels of aggregation of
      qualitative labels, each level corresponding to a distinct degree of qualitative
      representation. The developed TA-clustering algorithm provides an innovative way
      to cluster gene profiles. We show the developed method to be robust, efficient
      and to perform better than the standard hierarchical agglomerative clustering
      approach when dealing with temporal dislocations of time series. Results of the
      TA-clustering algorithm can be visualized as a three-level hierarchical tree of
      qualitative representations and as such easy to interpret. We demonstrate the
      utility of the proposed algorithm on a set of two simulated data sets and on a
      study of gene expression data from S. cerevisiae.

PMID- 15941670
TI  - Safety: the heart of the matter.
AB  - An integral part of evaluation of cardiac disease in modern day medicine is
      echocardiography. It has made great strides since the initial collaboration of
      Dr. Helmut Hertz and Dr. Inge Edler. In its modern day form, echocardiography
      maintains a legacy of a bedside utility while adopting many of the technologic
      advances ushered in by the digital era. As a result, it boasts a broad and
      growing spectrum of application including routine use in primary cardiac
      diagnosis and screening, therapeutic assessment, and guidance of interventional
      and surgical procedures. With the advent of ultrasound contrast agents it is now
      arguably the most complete 'one-stop' investigational tool to assess cardiac
      structure, function and perfusion. However, has it maintained its safety profile?
      The familiar and oft quoted dictum in medicine of "first do no harm" is of great
      importance for any diagnostic tool and patient safety should remain a primary
      consideration for any new investigational technique. In this issue Cosyns' et al.
      have examined whether some of the theoretical and in vitro experimental concerns
      surrounding myocardial injury during and following contrast echocardiography
      result in any detectable change in cardiac function.

PMID- 15941671
TI  - New reference values for echocardiographic dimensions of healthy Dutch children.
AB  - AIM: To renew the echocardiographic reference values of heart dimensions in
      healthy children. METHODS AND RESULTS: Group 1 consisted of 587 children, of
      which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500
      g, who visited the Pediatric Cardiology outclinic during the period January 2000
      till March 2004. All included children were diagnosed as normal, or as having
      innocent heart murmur. The second group was taken from an earlier study and
      comprised 160 children (77 boys and 83 girls). The echocardiographic measures
      were taken from conventional M-mode recording of the left ventricle (LV)
      parasternal long axis view. End diastolic septal (IVS) and LV posterior wall
      thickness (LVPW) and end diastolic as well as end systolic LV intracavity
      dimensions were retrospectively analyzed. The regression lines from all measured
      sizes are significantly different from those collected in the early eighties.
      Especially the thickness of the IVS is smaller. The regression lines are
      independent of gender. CONCLUSIONS: New reference values have been found which
      should replace the presently used ones. There is no difference between boys and
      girls. Why the muscular wall thicknesses are thinner than found 20 years ago
      needs to be further explored.

PMID- 15941672
TI  - Tissue Doppler imaging and conventional echocardiography after anthracycline
      treatment in adults: early and late alterations of left ventricular function
      during a prospective study.
AB  - AIM OF THE STUDY: To evaluate the short and long-term effects of anthracycline
      chemotherapy in adults using conventional echocardiography and pulsed tissue
      Doppler imaging (TDI). METHODS AND RESULTS: Twenty patients were included of
      which 16 had a complete follow up. They underwent an echocardiography before
      chemotherapy, 1-3 months and 3.5+/-0.6 years after the treatment. We recorded
      pulsed TDI at the mitral annulus, the basal segments of the left ventricular (LV)
      lateral and posterior walls; peak velocities in systole (Sm), early (Em) and late
      diastole and the isovolumic relaxation time (IVRT) were measured. The cumulative
      dose of doxorubicin was 211+/-82 g/m2. Early after anthracycline therapy, we
      observed changes in the diastolic LV function with a decrease of the mitral E
      peak velocity and TDI Em. At the late control, diastolic changes were more
      pronounced and associated with an alteration of the systolic function (LV
      ejection fraction and Sm). Four patients had a LV ejection fraction <50%; in
      these patients we observed a mitral annulus IVRT <80 ms at the early control;
      this could be of interest to predict later impairment of the LV ejection
      fraction. CONCLUSION: We found early changes in LV diastolic function and
      observed that late impairment of the LV ejection fraction occurred frequently
      after anthracycline therapy, despite normal systolic LV function during the first
      months of follow-up.

PMID- 15941673
TI  - Direct electron transfer reactions of laccases from different origins on carbon
      electrodes.
AB  - Electrochemical studies of laccases from basidiomycetes, i.e., Trametes hirsuta,
      Trametes ochracea, Coriolopsis fulvocinerea, Cerrena maxima, and Cerrena
      unicolor, have been performed. Direct (mediatorless) electrochemistry of laccases
      on graphite electrodes has been investigated with cyclic voltammetry, square wave
      voltammetry as well as potentiometry. For all mentioned high potential laccases
      direct electron transfer (DET) has been registered at spectrographic graphite and
      highly ordered pyrolytic graphite electrodes. The characteristics of DET
      reactions of the enzymes were analysed under aerobic and anaerobic conditions. It
      is shown that the T1 site of the laccase is the primary electron acceptor, both
      in solution (homogenous case) and at surface of the graphite electrode
      (heterogeneous case). A mechanism of ET for the process of the electro-reduction
      of oxygen at the laccase-modified graphite electrodes is proposed and the
      similarity of this heterogeneous process to the laccase catalysed oxygen
      reduction homogeneous reaction is concluded.

PMID- 15941674
TI  - DNA-PK-dependent phosphorylation of Ku70/80 is not required for non-homologous
      end joining.
AB  - The Ku70/80 heterodimer is a major player in non-homologous end joining and the
      repair of DNA double-strand breaks. Studies suggest that once bound to a DNA
      double-strand break, Ku recruits the catalytic subunit of the DNA-dependent
      protein kinase (DNA-PKcs) to form the DNA-dependent protein kinase holoenzyme
      complex (DNA-PK). We previously identified four DNA-PK phosphorylation sites on
      the Ku70/80 heterodimer: serine 6 of Ku70, serine 577 and 580 and threonine 715
      of Ku80. This raised the interesting possibility that DNA-PK-dependent
      phosphorylation of Ku could provide a mechanism for the regulation of non
      homologous end joining. Here, using mass spectrometry and phosphospecific
      antibodies we confirm that these sites are phosphorylated in vitro by purified
      DNA-PK. However, we show that neither DNA-PK nor the related protein kinase
      ataxia-telangiectasia mutated (ATM) is required for phosphorylation of Ku at
      these sites in vivo. Furthermore, Ku containing serine/threonine to alanine
      mutations at these sites was fully able to complement the radiation sensitivity
      of Ku negative mammalian cells indicating that phosphorylation at these sites is
      not required for non-homologous end joining. Interestingly, both Ku70 and Ku80
      were phosphorylated in cells treated with the protein phosphatase inhibitor
      okadaic acid under conditions known to inactivate protein phosphatase 2A-like
      protein phosphatases. Moreover, okadaic acid-induced phosphorylation of Ku80 was
      inhibited by nanomolar concentrations of the protein kinase inhibitor
      staurosporine. These results suggest that the phosphorylation of Ku70 and Ku80 is
      regulated by a protein phosphatase 2A-like protein phosphatase and a
      staurosporine sensitive protein kinase in vivo, but that DNA-PK-mediated
      phosphorylation of Ku is not required for DNA double-strand break repair.

PMID- 15941675
TI  - Protective responses of the newborn to hypoxia.
AB  - In human infants, spontaneous recovery from sleep related apnea or positional
      asphyxia can occur early with or without behavioral and/or cortical arousal or
      later as a result of autoresuscitation from "asphyxial coma" by hypoxic gasping.
      Because it occurs when early defense mechanisms are absent or fail to resolve
      apnea or positional asphyxia, autoresuscitation serves as a backup mechanism and
      is considered to be the last operative mechanism used by mammals to ensure
      survival during exposure to severe hypoxia. In this short review, factors will be
      considered that influence the onset, duration and number of potential
      autoresuscitation producing gasps as well as the integrated physiology of
      successful autoresuscitation and pathophysiology of failed autoresuscitation from
      hypoxic-induced apnea.

PMID- 15941676
TI  - Development of respiratory control: evolving concepts and perspectives.
AB  - The mechanisms underlying respiratory system immaturity in newborns have been
      investigated, both in vivo and in vitro, in humans and in animals. Immaturity
      affects breathing rhythmicity and its modulation by suprapontine influences and
      by afferents from central and peripheral chemoreceptors. Recent research has
      moved from bedside tools to sophisticated technologies, bringing new insights
      into the plasticity and genetics of respiratory control development. Genetic
      research has benefited from investigations of newborn mice having targeted
      deletions of genes involved in respiratory control. Genetic variability may
      govern the normal programming of development and the processes underlying
      adaptation to homeostasis disturbances induced by prenatal and postnatal insults.
      Studies of plasticity have emphasized the role of neurotrophic factors.
      Improvements in our understanding of the mechanistic effects of these factors
      should lead to new neuroprotective strategies for infants at risk for early
      respiratory control disturbances, such as apnoeas of prematurity, sudden infant
      death syndrome and congenital central hypoventilation syndrome.

PMID- 15941677
TI  - Automated on-line SPE LC-MS/MS method to quantitate 6beta-hydroxycortisol and
      cortisol in human urine: use of the 6beta-hydroxycortisol to cortisol ratio as an
      indicator of CYP3A4 activity.
AB  - A sensitive method for quantitation of urinary 6beta-hydroxycortisol (6beta-HC)
      and cortisol using on-line SPE and LC-MS/MS was developed and validated. Human
      urine samples were injected directly onto an on-line solid phase extraction
      apparatus, Prospekt-2, followed by HPLC separation and electrospray triple
      quadrupole LC-MS/MS detection. The inter-day precision for the 6beta-HC:cortisol
      ratio was 7-9%. The lower limit of quantitation was 1 and 0.2 ng/mL for 6beta-HC
      and cortisol, respectively. Using the method we observed a diurnal variation on
      the 6beta-HC:cortisol ratio in healthy volunteers with the maximal ratio observed
      in the 2-10 pm urine collection period.

PMID- 15941678
TI  - Obesity and the incidence of chronic diseases in Spain: a seemingly unrelated
      probit approach.
AB  - Western societies can reduce avoidable mortality and morbidity by better
      understanding the relationship between obesity and chronic disease. This paper
      examines the empirical association between obesity and the incidence of heart
      disease, diabetes, hypertension, and elevated cholesterol. We analyze a broadly
      representative Spanish dataset, the 1999 Survey on Disabilities, Impairments and
      Health Status, using a health production theoretical framework together with a
      seemingly unrelated probit model approach that controls for unobserved
      heterogeneity and endogeneity. Its findings provide evidence of a positive and
      significant, although specification-dependent, association between obesity and
      the prevalence of all chronic illness examined.

PMID- 15941679
TI  - Health and wealth. The late-20th century obesity epidemic in the U.S.
AB  - Obesity is a rapidly growing public health issue. This paper investigates
      obesity's relationship to individuals' wealth by analyzing data from a large U.S.
      longitudinal socio-economic survey. The results show a large negative association
      between BMI and White female's net worth, a smaller negative association for
      Black women and White males and no relationship for Black males. Weight changes
      and dieting also appear associated with wealth changes. Individuals who lose
      small amounts of weight experience little change in net worth, but those who lose
      large amounts of weight have a dramatically improved financial position, with
      Whites showing larger changes than Blacks.

PMID- 15941680
TI  - Cytokines as potential therapeutic targets for inflammatory skin diseases.
AB  - A network of pro-inflammatory cytokines is a central feature in the
      pathophysiology of cutaneous inflammatory diseases. Thus, the delineation of
      precise roles for particular cytokines and the development of cytokine-directed
      therapeutics have become areas of intense investigation. While anti-TNF
      therapeutics have proven to be effective for the treatment of psoriasis, clinical
      investigations have now begun with other cytokine-directed therapies, such as
      those targeting IFN-g, IL-12p40, and IL-18. In addition to therapeutics that
      target cytokines directly, strategies that target cytokine signaling pathways are
      in development too. In this short review, we summarize key findings from a recent
      workshop on cytokines as potential therapeutic targets for inflammatory skin
      diseases.

PMID- 15941681
TI  - Nonhuman primates are relevant models for research in hematology, immunology and
      virology.
AB  - Nonhuman primates have been used for biomedical research for several decades.
      They have proved to be models that are relevant to humans because of the high
      level of gene homology which underlies physiological and biochemical
      similarities. The similarity of monkeys to humans has been used to investigate
      pathophysiological mechanisms in hematology, immunology and virology. New
      therapeutic procedures can be assessed in primates by using materials, in
      particular pharmacological reagents, and methods designed for humans. The
      relevance of these models also relies on the use of species-specific pathogens
      and the availability of recombinant, homologous cytokines. The introduction of
      more and more sophisticated cell and gene therapy protocols in hematopoietic cell
      transplantation and immunotherapy requires the development of preclinical trials
      similar to clinical settings. For several decades now, baboons and
      cynomolgus/rhesus monkeys have been the most useful primate models in
      experimental hematology, and this has contributed to numerous therapeutic
      advances. Primate models of AIDS have been developed to study the pathogenesis,
      transmission and immune responses to infection, and to test vaccines and drugs.
      Primate research should be restricted in quantity, and mainly designed with the
      aim of removing uncertainty as to the safety and clinical benefit to the patient,
      of new biomedical protocols.

PMID- 15941682
TI  - High levels of circulating interleukin-10 in diabetic nephropathy patients.
AB  - AIMS: The aim of our study was to analyse the level of circulating interleukin-10
      (IL-10) and relate it to the grade of albuminuria in patients with diabetic
      nephropathy (DN) due to type 1 diabetes mellitus (DM). Since IL-10 has met the
      criteria for an anti-inflammatory and an immunosuppressive cytokine, its activity
      may be important for clinical outcome of DN. METHODS: The IL-10 level was
      measured by ELISA in serum samples from thirty patients with DN due to type 1 DM,
      and compared with thirty patients with type 1 DM without DN and a control group
      of thirty, healthy, age- and sex-matched people. RESULTS: We observed a greatly
      elevated concentration of circulating IL-10 in 30/30 DM patients with DN (mean
      140 pg/mL +/- 102), compared to DM patients without DN in whom IL-10 was
      detectable in only 11/30 patients (0.79 pg/mL +/- 1.24), and the group of healthy
      people in whom IL-10 was detectable in only 3/30 donors (0.92 pg/mL +/- 0.17). IL
      10 appeared to be the strongest independent predictor of albuminuria, followed by
      HbA1c, diastolic blood pressure and DN duration. There was a positive correlation
      between the values of IL-10 and albuminuria in DM patients with DN. The patients
      in the fourth quartile of albuminuria had a distinctly higher concentration of IL
      10 than those in the lower quartiles. CONCLUSIONS: The increased concentration of
      IL-10 in the serum samples from DM patients with DN seems to depend on the
      severity of the nephropathy. The excessive IL-10 production may indirectly
      contribute towards DN progression. On the other hand, it may explain the
      relatively long course of diabetic nephropathy.

PMID- 15941683
TI  - The sensitivity of renal cell carcinoma cells to interferon alpha correlates with
      p53-induction and involves Bax.
AB  - Interferon alpha (IFN-alpha) is an approved treatment in metastatic renal cell
      carcinoma (RCC). The underlying mechanisms are far from being clear, but are
      presumed to be a combination of stimulation of cell-mediated cytotoxicity, direct
      antiproliferative activity and antiangiogenic effects. Recently, the role of p53
      in the cellular response to IFN-alpha has been proposed in other tumor models
      (hepatoblastoma). We therefore studied the expression of p53 during IFN-alpha
      treatment using two freshly established RCC cell lines RCC5 and RCC7. While IFN
      alpha treatment significantly enhanced the expression of p53 in RCC7, no changes
      were observed in RCC5. Cell viability under IFN-alpha remained unchanged in both
      cell lines. Following gamma-irradiation, a p53-activating stimulus, an enhanced
      cell death was observed in IFN-alpha-treated RCC7 but not in RCC5. We further
      demonstrate that there were no changes in Bcl-2- and Bax-expression, two target
      genes regulated by p53. However, intracellular staining revealed that cell death
      induced by IFN-alpha and gamma-irradiation was preceded by a shift of Bax to the
      mitochondria in RCC7. Our results suggest a role of p53 and its downstream target
      Bax, in the control of RCC sensitivity to IFN-alpha.

PMID- 15941684
TI  - Effects of glucan treatment on the Th1/Th2 balance in patients with allergic
      rhinitis: a double-blind placebo-controlled study.
AB  - BACKGROUND: Allergic rhinitis (AR) is a disease characterized by IgE-mediated,
      allergic inflammation of the nasal mucosa. T helper (Th) 2 cells play an
      important role in the development of IgE-mediated diseases such as AR, with local
      overproduction of Th2 cytokines (IL-4, IL-5 and IL-13) at the site of allergic
      inflammation. Th1 cytokines (IL-12 and IFN-gamma) are known to suppress this Th2
      immune response, aiding the treatment of these diseases. Beta-1,3-1,6-glucan
      (Glucan) is an immunomodulator stimulating particularly the antitumor response.
      An efficient antitumor stimulation can be achieved through a Th1-mediated immune
      response. OBJECTIVE: The aim of this study was to investigate the effects of
      Glucan on the immunopathogenic processes in the microenvironment to determine if
      it reverses the Th2-mediated immune response in AR to Th1-mediated response.
      METHODS: 24 Olea europea mono-sensitized patients with AR were randomized into
      Glucan and placebo groups. The Glucan group consisted of 12 patients who received
      Glucan treatment for 12 weeks, while the placebo group of 12 patients received
      placebo during the same period. A nasal provocation test (NPT) with Olea europea
      was performed at the beginning and end of treatment, and nasal lavage followed
      the positive NPT. IL-4, IL-5, IFN-gamma and IL-12 levels and the eosinophil count
      (%) were measured in nasal lavage fluid (NLF) samples. Simultaneously, peripheral
      blood eosinophil % values were measured. RESULTS: After treatment, IL-4 and IL-5
      levels in NLF from the Glucan group were found to have decreased significantly (p
      = 0.027, p = 0.04; respectively), while IL-12 levels were found to have
      significantly increased (p = 0.008). However, IFN-gamma levels had not changed.
      On the other hand, none of the cytokine levels had changed significantly in the
      placebo group following treatment. Moreover, the percentage of eosinophils in the
      NLF was found to have decreased significantly after treatment in the Glucan group
      (p = 0.01), while that of the placebo group did not change. Peripheral blood
      percentage eosinophil levels had not changed significantly in any group.
      CONCLUSION: Th2-originated IL-4 and IL-5 levels responsible for the allergic
      inflammatory response in the microenvironment of patients with AR, are decreased
      with Glucan while levels of Th1-originated IL-12 are increased. Moreover,
      eosinophils, which are important effector cells of the inflammatory response, are
      decreased in the microenvironment. As a result, Glucan may have a role as an
      adjunct to standard treatment in patients with AR.

PMID- 15941685
TI  - Age-dependency of Plasmodium falciparum-specific and non-specific T cell cytokine
      responses in individuals from a malaria-endemic area.
AB  - In areas where Plasmodium falciparum malaria is highly endemic, naturally
      acquired immunity develops slowly with increasing age. The mechanisms that lead
      to this protective immunity against P. falciparum are under intense
      investigation, as they might serve as models for the development of an efficient
      vaccine. In this study, we aimed to investigate the potential contribution of
      cell-mediated immune responses to the build-up of anti-malarial immunity by
      comparing the phenotypes and frequencies of both P. falciparum-specific and non
      specific, cytokine-expressing T cells in a cross-sectional study of healthy
      children and adults, living in a malaria-endemic area in Central Africa. An
      increased capacity of CD3+ cells to produce interferon (IFN)-gamma and tumor
      necrosis factor (TNF)-alpha, and of the TCRgammadelta+ subset to produce TNF
      alpha was seen in adults after stimulation of peripheral blood mononuclear cells
      (PBMC) with a late-stage, schizont-rich, parasite preparation. Mitogenic
      stimulation with PMA and ionomycin induced much higher frequencies of IFN-gamma-
      and TNF-alpha-expressing CD4+, CD8+ as well as TCRgammadelta+ cells in adults,
      while differences for interleukin (IL)-2 expression were restricted to CD4+ and
      CD8+ T cells. For IL-10, neither specific nor non-specific stimulations of PBMC
      were associated with significant age-dependent alterations. Impressive increases
      in the capacity to produce P. falciparum-specific and non-specific IFN-gamma and
      TNF-alpha appear to be the main cellular correlates of naturally acquired
      immunity in Central Africa.

PMID- 15941687
TI  - Clinical significance of matrix metalloproteinases activity in acute myocardial
      infarction.
AB  - Matrix metalloproteinases (MMP) degrade myocardial fibrillar collagen in acute
      myocardial infarction (MI) patients. Their activity is tightly controlled in
      normal myocardium by a family of closely related tissue inhibitors known as TIMP.
      An imbalance in their activity might contribute to post-MI remodeling. Plasma
      levels of MMP-1, TIMP-1 and MMP-1/TIMP-1 complex were measured, using relevant
      ELISA kits, in 24 (22 males-2 females), acute MI patients with a mean age 59 +/-
      14 years. Blood samples were taken on admission (0 h), and 3 h, 6 h, 9 h, 18 h,
      24 h, 36 h, 48 h, 3rd, 4th, 5th, 7th, 15th, 30th days after MI. All patients
      underwent coronary arteriography with ventriculography for estimation of left
      ventricular ejection fraction (LVEF) and extent of coronary artery diseases, and
      echocardiographic study for measuring end-diastolic diameter (EDD). Ten patients
      with an LVEF < 45%, an EDD > 47.5 mm, and heart failure symptoms were included in
      group A and compared against 12 patients with an LVEF > 45% an EDD < 47.5 mm in
      group B. Mean plasma concentrations of MMP-1 were higher by 21% in group A (1.3
      +/- 0.2 ng/mL) compared to group B (1 +/- 0.1 ng/mL) over the total study period.
      TIMP-1 plasma concentrations showed very little difference between the 2 groups,
      (704 +/- 213 ng/mL versus 691 +/- 165 ng/mL, (6%)). Finally, plasma
      concentrations of MMP-1/TIMP-1 complex were lower by -36% in group A with a mean
      value of 2.7 +/- 0.6 ng/mL versus 3.7 +/- 0.5 ng/mL in group B. Mean values for
      the differences were significant at time points 0, 6, 18, 24 and 48 hours for MMP
      1 (p < 0.036), and on 48 h and the 4th day for MMP-1/TIMP-1 complex (p < 0.031).
      Moreover, a good correlation was found between plasma concentrations of creatine
      kinase (CK) and MMP-1 at 18 h (r = 0.422, p = 0.041) and on the 4th day (r =
      0.67, p = 0.046), and TIMP-1 on the 4th day (r = 0.67, p = 0.047). Additionally,
      mean values for LVEF were 35.8 +/- 8.8% in group A versus 51.2 +/- 1.8% (p =
      0.00014) in group B. Also, the EDD in-group A was 52.1 +/- 6.9 mm versus 42.9 +/-
      3.2 mm in group B (p = 0.00013). In acute MI patients, increased MMP-1, with no
      change in TIMP-1, is associated with left ventricular dysfunction and dilatation,
      suggesting that increased collagenolytic activity contributes to loss of LV
      function.

PMID- 15941686
TI  - 4-Hydroxy-oxyphenbutazone is a potent inhibitor of cytokine production.
AB  - 4-Hydroxy-oxyphenbutazone (4OH-OPB), is currently in phase II trials for its
      immunosuppressive effect in patients with rheumatoid arthritis. 4OH-OPB and other
      compounds related to phenylbutazone were tested for their effect on in vitro
      cytokine production by monocytes and lymphocytes present in peripheral
      mononuclear cells (PBMC) or whole blood (WB) cultures, and compared against
      phenylbutazone and oxyphenbutazone, two known anti-inflammatory drugs. In PBMC
      cultures, 4OH-OPB was by far the most potent inhibitor, and both monokines and
      Th1 and Th2 lymphokines were efficiently inhibited at low concentrations. In WB
      cultures, 4OH-OPB was less effective than in PBMC cultures, but was still the
      best inhibitor of lymphokine production and, furthermore, was the only inhibitor
      of monokine production. The increase in 4OH-OPB concentration needed to induce
      the same inhibition of cytokine production in WB as in PBMC culture could be
      mimicked by the addition of erythrocytes to the PBMC cultures. Experiments with
      radioactively-labeled 4OH-OPB suggest that 4OH-OPB is taken up very rapidly into
      erythrocytes and is secreted by the erythrocytes with much slower kinetics via a
      multidrug-resistance-associated protein. The secreted compound is most likely
      structurally different from 4OH-OPB, as in PBMC and WB cultures, the inhibition
      of cytokine production seems to be caused by a different mechanism. In PBMC
      cultures, the inhibition of cytokine production is accompanied by a loss of cell
      viability, while this is not the case when 4OH-OPB inhibits cytokine production
      in WB. Our data suggest that 4OH-OPB may be useful as an immunosuppressive drug
      for patients with inflammatory diseases.

PMID- 15941688
TI  - Interleukin-6 expression during normal maturation of the mouse testis.
AB  - In this study, we examined the cellular origin and the expression levels of
      interleukin-6 (IL-6) during normal maturation of mouse testis. The levels of IL-6
      (protein and mRNA) were higher in testicular homogenates of sexually immature
      than mature mice. Immunohistochemical staining of testicular tissues of sexually
      immature and adult mice show that testicular germ cells, at different stages of
      differentiation, Leydig cells/interstitial cells and peritubular cells express IL
      6. Our results demonstrate, for the first time, overexpression of IL-6 in
      testicular tissues of immature mice, as compared to mature mice, as well as the
      expression of IL-6 in germ cells of testicular tissues of adult and sexually
      immature mice. Thus, our results may indicate the involvement of the endocrine
      system (gonadotropins and testosterone) in the regulation of IL-6, which is
      involved in the regulation of testicular development, functions and
      spermatogenesis.

PMID- 15941689
TI  - Testicular interleukin-6 response to systemic inflammation.
AB  - Spermatogenesis is a highly controlled process of proliferation, meiosis, and
      differentiation. Systemic infection and chronic inflammation can impair
      testicular steroidogenesis and spermatogenesis. In this study, we examined the
      effect of systemic infection--intraperitoneal (i.p.) injection of
      lipopolysaccharide (LPS)--on the expression levels of IL-6 in the testis of
      sexually immature and adult mice. IL-6 levels in testicular homogenates of
      immature mice were significantly higher than in mature mice (both protein and RNA
      levels), before and after LPS injection. Injection of LPS (i.p.) into mature mice
      over 3 hours, significantly increased testicular IL-6 protein and mRNA levels (as
      demonstrated by ELISA and RT-PCR respectively) compared to the control group.
      Injection of LPS over 24 hours significantly increased IL-6 mRNA expression, but
      it did not significantly affect IL-6 protein levels in the homogenates. In
      contrast, stimulation of immature mice with LPS (2, 20 or 100 microg/mL) over 3
      hours or LPS (2 or 20 microg/mL) over 24 hours, significantly increased
      testicular IL-6 (both protein and mRNA expression). The levels of testicular IL-6
      (protein) in the homogenates were not significantly increased after stimulation
      with 100 microg/mL over 24 hours, but they were significantly increased at the
      mRNA level. Our results demonstrate, for the first time, the over-expression of
      IL-6 in testicular homogenates of mature and immature mice following systemic
      inflammation (i.p. injection of LPS). These results suggest the possibility of
      the involvement of systemic infection/inflammation, through the elevation of
      testicular IL-6, in testicular functions, which may affect male fertility. Also,
      high levels of IL-6 during pathological conditions, could play a role in
      protecting testicular tissue.

PMID- 15941690
TI  - Summaries for patients. The health of Gulf War veterans.

PMID- 15941691
TI  - Summaries for patients. Potential savings with substitution of generic drugs for
      brand-name drugs.

PMID- 15941692
TI  - Summaries for patients. Description of a hepatitis C outbreak in a cancer clinic.

PMID- 15941693
TI  - Summaries for patients. Can thorough cleaning of endoscopes prevent transmission
      of hepatitis C virus infection?

PMID- 15941694
TI  - Gulf War veterans' health: medical evaluation of a U.S. cohort.
AB  - BACKGROUND: United States military personnel reported various symptoms after
      deployment to the Persian Gulf during the 1991 Gulf War. However, the symptoms'
      long-term prevalence and association with deployment remain controversial.
      OBJECTIVE: To assess and compare the prevalence of selected medical conditions in
      a national cohort of deployed and nondeployed Gulf War veterans who were
      evaluated by direct medical and teledermatologic examinations. DESIGN: A cross
      sectional prevalence study performed 10 years after the 1991 Gulf War. SETTING:
      Veterans were examined at 1 of 16 Veterans Affairs medical centers. PARTICIPANTS:
      Deployed (n = 1061) and nondeployed (n = 1128) veterans of the 1991 Gulf War.
      MEASUREMENTS: Primary outcome measures included fibromyalgia, the chronic fatigue
      syndrome, dermatologic conditions, dyspepsia, physical health-related quality of
      life (Short Form-36 [SF-36]), hypertension, obstructive lung disease,
      arthralgias, and peripheral neuropathy. RESULTS: Of 12 conditions, only 4
      conditions were more prevalent among deployed than nondeployed veterans:
      fibromyalgia (deployed, 2.0%; nondeployed, 1.2%; odds ratio, 2.32 [95% CI, 1.02
      to 5.27]); the chronic fatigue syndrome (deployed, 1.6%; nondeployed 0.1%; odds
      ratio, 40.6 [CI, 10.2 to 161]); dermatologic conditions (deployed, 34.6%;
      nondeployed, 26.8%; odds ratio, 1.38 [CI, 1.06 to 1.80]), and dyspepsia
      (deployed, 9.1%; nondeployed, 6.0%; odds ratio, 1.87 [CI, 1.16 to 2.99]). The
      mean physical component summary score of the SF-36 for deployed and nondeployed
      veterans was 49.3 and 50.8, respectively. LIMITATIONS: Relatively low
      participation rates introduce potential participation bias, and deployment
      related illnesses that resolved before the research examination could not, by
      design, be detected. CONCLUSIONS: Ten years after the Gulf War, the physical
      health of deployed and nondeployed veterans is similar. However, Gulf War
      deployment is associated with an increased risk for fibromyalgia, the chronic
      fatigue syndrome, skin conditions, dyspepsia, and a clinically insignificant
      decrease in the SF-36 physical component score.

PMID- 15941695
TI  - Potential savings from substituting generic drugs for brand-name drugs: medical
      expenditure panel survey, 1997-2000.
AB  - BACKGROUND: Generic substitution is one mechanism of curtailing prescription drug
      expenditures. Limited information is available about the potential savings
      associated with generic substitution. OBJECTIVE: To estimate the potential
      savings associated with broad substitution of generic drugs. DESIGN: Cross
      sectional, nationally representative survey of noninstitutionalized adults.
      SETTING: United States. PARTICIPANTS: Adults included in the Medical Expenditure
      Panel Survey Household Component, 1997-2000. MEASUREMENTS: Use of a multisource
      drug (that is, a drug available in a brand-name and > or =1 generic formulation)
      or a generic drug and the potential cost savings associated with broad generic
      substitution for all multisource products. RESULTS: Fifty-six percent of all
      outpatient drugs were multisource products, accounting for 41% of total
      outpatient drug expenditures. Of these multisource drugs, 61% were dispensed as a
      generic. If a generic had been substituted for all corresponding brand-name
      outpatient drugs in 2000, the median annual savings in drug expenditures per
      person would have been 45.89 dollars (interquartile range, 10.35 dollars to
      158.06) for adults younger than 65 years of age and 78.05 dollars (interquartile
      range, 19.94 dollars to 241.72 dollars) for adults at least 65 years of age. In
      these age groups, the national savings would have been 5.9 billion dollars (95%
      CI, 5.5 billion dollars to 6.2 billion dollars) and 2.9 billion dollars (CI, 2.6
      billion dollars to 3.1 billion dollars), respectively, representing approximately
      11% of drug expenditures. LIMITATIONS: Specific information about an individual's
      formulary was not available, so the authors could not estimate how much of the
      potential savings would benefit an individual or his or her health plan.
      CONCLUSION: Although broad substitution of generic drugs would affect only a
      modest percentage of drug expenditures, it could result in substantial absolute
      savings.

PMID- 15941696
TI  - An outbreak of hepatitis C virus infections among outpatients at a
      hematology/oncology clinic.
AB  - BACKGROUND: Approximately 2.7 million persons in the United States have chronic
      hepatitis C virus (HCV) infection. Health care-associated HCV transmission can
      occur if aseptic technique is not followed. The authors suspected a health care
      associated HCV outbreak after the report of 4 HCV infections among patients at
      the same hematology/oncology clinic. OBJECTIVE: To determine the extent and
      mechanism of HCV transmission among clinic patients. DESIGN: Epidemiologic
      analysis through a cohort study. SETTING: Hematology/oncology clinic in eastern
      Nebraska. PARTICIPANTS: Patients who visited the clinic from March 2000 through
      December 2001. MEASUREMENTS: HCV infection status, relevant medical history, and
      clinic-associated exposures. Bivariate analysis and logistic regression were used
      to identify risk factors for HCV infection. RESULTS: Of 613 clinic patients
      contacted, 494 (81%) underwent HCV testing. The authors documented infection in
      99 patients who lacked previous evidence of HCV infection; all had begun
      treatment at the clinic before July 2001. Hepatitis C virus genotype 3a was
      present in all 95 genotyped samples and presumably originated from a patient with
      chronic hepatitis C who began treatment in March 2000. Infection with HCV was
      statistically significantly associated with receipt of saline flushes (P <
      0.001). Shared saline bags were probably contaminated when syringes used to draw
      blood from venous catheters were reused to withdraw saline solution. The clinic
      corrected this procedure in July 2001. LIMITATION: The delay between outbreak and
      investigation (>1 year) may have contributed to an underestimate of cases.
      CONCLUSIONS: This large health care-associated HCV outbreak was related to shared
      saline bags contaminated through syringe reuse. Effective infection-control
      programs are needed to ensure high standards of care in outpatient care
      facilities, such as hematology/oncology clinics.

PMID- 15941697
TI  - Digestive endoscopy is not a major risk factor for transmitting hepatitis C
      virus.
AB  - BACKGROUND: The potential role of digestive endoscopy as a mode for transmission
      of hepatitis C virus (HCV) is controversial. OBJECTIVE: To evaluate the role of
      digestive endoscopy in transmitting HCV by comparing the incidence of HCV
      infection in a cohort of patients undergoing endoscopy and in a cohort of blood
      donors. DESIGN: Prospective cohort study. SETTING: 3 endoscopic units and 2 blood
      banks in northwestern Italy. PATIENTS: The potentially exposed cohort consisted
      of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008
      patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for
      anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51,230
      healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same
      area and during the same time period; 38,280 of them (75%) were tested again for
      anti-HCV 6 to 48 months after the first blood donation (95,317 person-years of
      observation). MEASUREMENTS: Differences in the anti-HCV seroconversion rate
      between the exposed cohort (patients undergoing endoscopy) and the unexposed
      cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme
      immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA
      by polymerase chain reaction. RESULTS: All 8260 persons undergoing endoscopy
      remained negative for anti-HCV 6 months after the procedure (risk per 1000
      persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who
      underwent endoscopy with the same instrument previously used on HCV carriers
      showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four
      blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49
      years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person
      years]); each had undergone minor surgery before the second test. LIMITATIONS: In
      the endoscopy cohort, 8.3% of patients were lost to follow-up. CONCLUSIONS: These
      findings support the hypothesis that properly performed digestive endoscopy is
      not a major risk factor for the transmission of HCV.

PMID- 15941698
TI  - Over-the-counter statins.
AB  - In late 2004, the British government decided to allow a lipid-lowering agent to
      be sold as an over-the-counter medication. In contrast, the U.S. Food and Drug
      Administration recently decided not to do so. The United States and other
      countries will soon face similar decisions for other statins. Although statins
      have infrequent side effects and have been shown to be effective in moderate-risk
      primary prevention populations, many questions remain unanswered about their
      effectiveness at lower doses in over-the-counter use, the ability of patients to
      self-select themselves for appropriate therapy, and the social and economic
      implications associated with this method of distribution for preventive
      medications. A rational policy decision concerning over-the-counter statin use
      will require an effectiveness trial to provide data on how such drugs would be
      used in this context, as well as on the clinical outcomes that could be expected
      from this novel "route of administration."

PMID- 15941699
TI  - Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria
      gonorrhoeae.
AB  - BACKGROUND: Testing of urine samples is noninvasive and could overcome several
      barriers to screening for chlamydial and gonococcal infections, but most test
      samples are obtained directly from the cervix or urethra. PURPOSE: To
      systematically review studies that assessed the sensitivity and specificity of
      nucleic acid amplification tests for Chlamydia trachomatis and Neisseria
      gonorrhoeae in urine specimens and to compare test characteristics according to
      type of assay, site of sample collection, presence of symptoms, disease
      prevalence, and characteristics of the reference standard. DATA SOURCES: Relevant
      studies in all languages were identified by searching the MEDLINE database
      (January 1991 to December 2004) and by hand-searching the references of
      identified articles and relevant journals. STUDY SELECTION: Studies were selected
      that evaluated 1 of 3 commercially available nucleic acid amplification tests,
      included data from tests of both a urine sample and a traditional sample
      (obtained from the cervix or urethra), and used an appropriate reference
      standard. DATA EXTRACTION: From 29 eligible studies, 2 investigators
      independently abstracted data on sample characteristics, reference standard,
      sensitivity, and specificity. DATA SYNTHESIS: Articles were assessed
      qualitatively and quantitatively. Summary estimates for men and women were
      calculated separately for chlamydial and gonococcal infections and were
      stratified by assay and presence of symptoms. The pooled study specificities of
      each of the 3 assays exceeded 97% when urine samples were tested, for both
      chlamydial infection and gonorrhea and in both men and women. The pooled study
      sensitivities for the polymerase chain reaction, transcription-mediated
      amplification, and strand displacement amplification assays, respectively, were
      83.3%, 92.5%, and 79.9% for chlamydial infections in women; 84.0%, 87.7%, and
      93.1% for chlamydial infections in men; and 55.6%, 91.3%, and 84.9% for
      gonococcal infections in women. The pooled specificity of polymerase chain
      reaction to gonococcal infections in men was 90.4%. In subgroup analyses, the
      sensitivity did not vary according to the prevalence of infection or the presence
      of symptoms but did vary according to the reference standard used. LIMITATIONS:
      Few published studies present data on the transcription-mediated amplification or
      strand displacement amplification assays, and few studies report data from
      asymptomatic patients or low-prevalence groups. CONCLUSIONS: Results of nucleic
      acid amplification tests for C. trachomatis on urine samples are nearly identical
      to those obtained on samples collected directly from the cervix or urethra.
      Although all 3 assays can also be used to test for N. gonorrhoeae, the
      sensitivity of the polymerase chain reaction assay in women is too low to
      recommend its routine use to test for gonorrhea in urine specimens.

PMID- 15941700
TI  - Continuing controversies in the management of thyroid nodules.
AB  - Although thyroid nodules are common, few are malignant and require surgical
      treatment. A systematic approach to their evaluation is important to avoid
      unnecessary surgery. Fine-needle aspiration biopsy has resulted in substantial
      improvements in diagnostic accuracy, cost reductions, and higher malignancy yield
      at time of surgery. The preferred approach when repeated fine-needle aspiration
      biopsy fails to yield an adequate specimen remains a challenge. Management of
      patients with nodules "suspicious for follicular neoplasm" is difficult, since
      only 15% to 20% of such lesions have been shown to be malignant.
      Immunohistochemical markers, such as galectin-3 and human bone marrow endothelial
      cell (HBME-1), have shown promise in preliminary studies. Routine calcitonin
      measurement in patients with thyroid nodules has been advocated for early
      detection of medullary thyroid cancer. However, the low frequency of this cancer,
      coupled with the high cost associated with case detection, has resulted in a lack
      of general acceptance of this recommendation.

PMID- 15941701
TI  - High and rising health care costs. Part 2: technologic innovation.
AB  - Technologic innovation, in combination with weak cost-containment measures, is a
      major factor in high and rising health care costs. Evidence suggests that
      improved health care technologies generally increase rather than reduce health
      care expenditures. Greater availability of such technologies as magnetic
      resonance imaging, computed tomography, coronary artery bypass graft,
      angioplasty, cardiac and neonatal intensive care units, positron emission
      tomography, and radiation oncology facilities is associated with greater per
      capita use and higher spending on these services. Because the spread of new
      technologies is relatively unrestrained in the United States, many of these
      technologies are used to a greater extent than in other nations, and the United
      States thereby incurs higher health care costs. Nations with a greater degree of
      health system integration have relied on expenditure controls and global budgets
      to control costs. Although diffusion of technology takes place more slowly in
      more tightly budgeted systems, the use of innovative technologies in those
      systems tends to catch up over time.

PMID- 15941702
TI  - Unexplained suffering in the aftermath of war.

PMID- 15941703
TI  - Patient-to-patient transmission of hepatitis C virus.

PMID- 15941704
TI  - An editorial update: should she take aspirin?

PMID- 15941705
TI  - A good man.

PMID- 15941706
TI  - Balancing the risks and benefits of fish consumption.

PMID- 15941707
TI  - Rhabdomyolysis with cardiac involvement and acute renal failure in a patient
      taking rosuvastatin and fenofibrate.

PMID- 15941708
TI  - Other disorders that mimic infectious cellulitis.

PMID- 15941709
TI  - Balancing the risks and benefits of fish consumption.

PMID- 15941710
TI  - Thyroid hormone regulates the hypotriglyceridemic gene APOA5.
AB  - The apolipoprotein AV gene (APOA5) is a key determinant of plasma triglyceride
      levels, a major risk factor for coronary artery disease and a biomarker for the
      metabolic syndrome. Since thyroid hormones influence very low density lipoprotein
      triglyceride metabolism and clinical studies have demonstrated an inverse
      correlation between thyroid status and plasma triglyceride levels, we examined
      whether APOA5 is regulated by thyroid hormone. Here we report that 3,5,3'-triiodo
      L-thyronine (T3) and a synthetic thyroid receptor beta (TRbeta) ligand increase
      APOA5 mRNA and protein levels in hepatocytes. Our data revealed that T3-activated
      TR directly regulates APOA5 promoter through a functional direct repeat separated
      by four nucleotides (DR4). Interestingly, we show that upstream stimulatory
      factor 1, a transcription factor associated with familial combined hyperlipidemia
      and elevated triglyceride levels in humans, and upstream stimulatory factor 2
      cooperate with TR, resulting in a synergistic activation of APOA5 promoter in a
      ligand-dependent manner via an adjacent E-box motif. In rats, we observed that
      apoAV levels declines with thyroid hormone depletion but returned to normal
      levels upon T3 administration. In addition, treatments with a TRbeta-selective
      agonist increased apoAV and diminished triglyceride levels. The identification of
      APOA5 as a T3 target gene provides a new potential mechanism whereby thyroid
      hormones can influence triglyceride homeostasis. Additionally, these data suggest
      that TRbeta may be a potential pharmacological target for the treatment of
      hypertriglyceridemia.

PMID- 15941711
TI  - A critical control element for interleukin-4 memory expression in T helper
      lymphocytes.
AB  - Naive T helper (Th) lymphocytes are induced to express the il4 (interleukin-4)
      gene by simultaneous signaling through the T cell receptor and the interleukin
      (IL)-4 receptor. Upon restimulation with antigen, such preactivated Th
      lymphocytes can reexpress the il4 gene independent of IL-4 receptor signaling.
      This memory for expression of the il4 gene depends on epigenetic modification of
      the il4 gene locus and an increased expression of GATA-3, the key transcription
      factor for Th2 differentiation. Here, we have identified a phylogenetically
      conserved sequence, the conserved intronic regulatory element, in the first
      intron of the il4 gene containing a tandem GATA-3 binding site. We show that GATA
      3 binds to this sequence in a position- and orientation-dependent manner, in
      vitro and in vivo. DNA demethylation and histone acetylation of this region
      occurs early and selectively in differentiating, IL-4-secreting Th2 lymphocytes.
      Deletion of the conserved element by replacement of the first exon and part of
      the first intron of the il4 gene with gfp leads to a defect in the establishment
      of memory for expression of IL-4, in that reexpression of IL-4 still requires
      costimulation by exogenous IL-4. The conserved intronic regulatory element thus
      links the initial epigenetic modification of the il4 gene to GATA-3 and serves as
      a genetic control element for memory expression of IL-4.

PMID- 15941712
TI  - Alpha-synuclein alters proteasome function, protein synthesis, and stationary
      phase viability.
AB  - Alpha-synuclein appears to play a role in mediating neurotoxicity in a number of
      neurodegenerative disorders, collectively referred to as synucleinopathies. Most
      of these disorders are associated with aging and a probable impairment of the
      proteasome-proteolytic pathway, although the relationship between aging,
      proteasome inhibition, and alpha-synuclein toxicity has not been fully
      elucidated. Recent studies suggest that yeast may provide a useful system for
      studying the biology and toxicity of alpha-synuclein in mitotic cells,
      recapitulating many features observed in the various synucleinopathy disorders.
      Additional studies indicate that the stationary phase model of aging in yeast
      provides a useful system for understanding the biochemistry and regulation of
      aging in post-mitotic cells. In the present study we examined the effect of wild
      type and mutant alpha-synuclein (A30P) on multiple aspects of proteasome
      homeostasis, protein synthesis, as well as the ability of cells to survive
      stationary phase aging. These data demonstrate that alpha-synuclein alters
      proteasome composition, impairs proteasome-mediated protein degradation, impairs
      protein synthesis, and impairs the ability of cells to withstand stationary phase
      aging. Interestingly, alpha-synuclein had little effect on intracellular
      proteasome content or protein ubiquitination, and did not increase the
      vulnerability of cells to a variety of stressors. Together, these data suggest
      that yeast may be useful for understanding the ability of alpha-synuclein to
      impair proteasome-mediated protein degradation, as well as for understanding the
      basis for age-related alpha-synuclein cytotoxicity.

PMID- 15941713
TI  - Vascular endothelial growth factor receptor-2: counter-regulation by the
      transcription factors, TFII-I and TFII-IRD1.
AB  - The vascular endothelial growth factor receptor-2 (VEGFR-2/KDR/flk-1) functions
      as the primary mediator of vascular endothelial growth factor activation in
      endothelial cells. Regulation of VEGFR-2 expression appears critical in
      mitogenesis, differentiation, and angiogenesis. Transcriptional regulation of the
      VEGFR-2 is complex and may involve multiple putative upstream regulatory elements
      including E boxes. Transcript initiation is dependent on an initiator (Inr)
      element flanking the transcriptional start site. The transcription factor, TFII
      I, enhances VEGFR-2 transcription in an Inr-dependent fashion. TFII-I is unusual
      both structurally and functionally. The TFII-I transcription factor family
      members contain multiple putative DNA binding domains. Functionally, TFII-I acts
      at both the basal, Inr element as well as at several distinct upstream regulatory
      sites. It has been postulated that the structure of TFII-I might allow
      simultaneous interaction with both basal and regulatory sites in a given
      promoter. As TFII-I is known to act at regulatory sites including E boxes as well
      as at the basal Inr element, we evaluated the possibility of Inr-independent TFII
      I activation of the VEGFR-2 promoter. We found that an Inr-mutated VEGFR-2
      reporter construct retains TFII-I-stimulated activity. We demonstrated that TFII
      I binds to both the Inr and to three regulatory E boxes in the human VEGFR-2
      promoter. In addition, reduction in TFII-I expression by siRNA results in
      decreased VEGFR-2 expression. We also describe counter-regulation of the VEGFR-2
      promoter by TFII-IRD1. We found that TFII-I is capable of acting at both basal
      and regulatory sites in one promoter and that the human VEGFR-2 promoter is
      functionally counter-regulated by TFII-I and TFII-IRD1.

PMID- 15941714
TI  - A fascination with enzymes: the journey not the arrival matters.

PMID- 15941715
TI  - Time-dependent changes in the denatured state(s) influence the folding mechanism
      of an all beta-sheet protein.
AB  - Newt fibroblast growth factor (nFGF-1) is an approximately 15-kDa all beta-sheet
      protein devoid of disulfide bonds. Urea-induced equilibrium unfolding of nFGF-1,
      monitored by steady state fluorescence and far-UV circular dichroism
      spectroscopy, is cooperative with no detectable intermediate(s). Urea-induced
      unfolding of nFGF-1 is reversible, but the percentage of the protein recovered in
      the native state depends on the time of incubation of the protein in the
      denaturant. The yield of the protein in the native state decreases with the
      increase in time of incubation in the denaturant. The failure of the protein to
      refold to its native state is not due to trivial chemical reactions that could
      possibly occur upon prolonged incubation in the denaturant. (1)H-(15)N
      heteronuclear single quantum coherence (HSQC) spectra, limited proteolytic
      digestion, and fluorescence data suggest that the misfolded state(s) of nFGF-1
      has structural features resembling that of the denatured state(s). GroEL, in the
      presence of ATP, is observed to rescue the protein from being trapped in the
      misfolded state(s). (1)H-(15)N HSQC data of nFGF-1, acquired in the denatured
      state(s) (in 8 m urea), suggest that the protein undergoes subtle time-dependent
      structural changes in the denaturant. To our knowledge, this report for the first
      time demonstrates that the commitment to adapt unproductive pathways leading to
      protein misfolding/aggregation occurs in the denatured state ensemble.

PMID- 15941716
TI  - Molecular dissection of PINCH-1 reveals a mechanism of coupling and uncoupling of
      cell shape modulation and survival.
AB  - How cells couple and uncouple regulation of cellular processes such as shape
      change and survival is an important question in molecular cell biology. PINCH-1,
      a widely expressed protein consisting of five LIM domains and a C-terminal tail,
      is an essential focal adhesion protein with multiple functions including
      regulation of the integrin-linked kinase (ILK) level, cell shape, and survival
      signaling. We show here that the LIM1-mediated interaction with ILK regulates all
      these three processes. By contrast, the LIM4-mediated interaction with Nck-2,
      which regulates cell morphology and migration, is not required for the control of
      the ILK level and survival. Remarkably, a short 15-residue tail C-terminal to
      LIM5 is required for both cell shape modulation and survival, albeit it is not
      required for the control of the ILK level. The C-terminal tail not only regulates
      PINCH-1 localization to focal adhesions but also functions after it localizes
      there. These findings suggest that PINCH-1 functions as a molecular platform for
      coupling and uncoupling diverse cellular processes via overlapping but yet
      distinct domain interactions.

PMID- 15941717
TI  - Adenylate kinase of Escherichia coli, a component of the phage T4 dNTP synthetase
      complex.
AB  - Adenylate kinase, which catalyzes the reversible ATP-dependent phosphorylation of
      AMP to ADP and dAMP to dADP, can also catalyze the conversion of nucleoside
      diphosphates to the corresponding triphosphates. Lu and Inouye (Lu, Q., and
      Inouye, M. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 5720-5725) showed that an
      Escherichia coli ndk mutant, lacking nucleoside diphosphate kinase, can use
      adenylate kinase as an alternative source of nucleoside triphosphates.
      Bacteriophage T4 can reproduce in an Escherichia coli ndk mutant, implying that
      adenylate kinase can meet a demand for deoxyribonucleoside triphosphates that
      increases by up to 10-fold as a result of T4 infection. In terms of kinetic
      linkage and specific protein-protein associations, NDP kinase is an integral
      component of T4 dNTP synthetase, a multienzyme complex containing phage-coded
      enzymes, which facilitates the synthesis of dNTPs and their flow into DNA. Here
      we asked whether, by similar criteria, adenylate kinase of the host cell is also
      a specific component of the complex. Experiments involving protein affinity
      chromatography, immunoprecipitation, optical biosensor measurements, and
      glutathione S-transferase pulldowns demonstrated direct interactions between
      adenylate kinase and several phage-coded enzymes, as well as E. coli nucleoside
      diphosphate kinase. These results identify adenylate kinase as a specific
      component of the complex. The rate of DNA synthesis after infection of an ndk
      mutant was found to be about 40% of the rate seen in wild-type infection,
      implying that complementation of the missing NDP kinase function by adenylate
      kinase is fairly efficient, but that adenylate kinase becomes rate-limiting for
      DNA synthesis when it is the sole source of dNTPs.

PMID- 15941718
TI  - CTCF regulates growth and erythroid differentiation of human myeloid leukemia
      cells.
AB  - CTCF is a transcription factor and a candidate tumor suppressor that contains a
      DNA-binding domain composed of 11 zinc fingers. We reported previously that CTCF
      is differentially regulated during differentiation of human myeloid leukemia
      cells. In this study we aimed to investigate the role of CTCF in myeloid cell
      differentiation. A human cell line, K562, that can be chemically induced to
      differentiate into various hematopoietic lineages was chosen as a model system
      for this study. Several K562 cell lines with constitutive and conditional
      expression of CTCF have been generated. By using these model systems we
      demonstrated that: (i) ectopic expression of CTCF in K562 cells led to growth
      retardation and promotion of differentiation into the erythroid lineage; (ii)
      CTCF knock-down significantly inhibited differentiation of K562 cells into
      erythroid lineage; (iii) differentiation of K562 into the megakaryocytic lineage
      was not significantly affected; and (iv) down-regulation of MYC has been
      identified as one of the mechanisms by which CTCF promotes erythroid
      differentiation. Taken together our results demonstrate that CTCF is involved in
      the control of myeloid cell growth and differentiation.

PMID- 15941719
TI  - Oxidative stress-dependent structural and functional switching of a human 2-Cys
      peroxiredoxin isotype II that enhances HeLa cell resistance to H2O2-induced cell
      death.
AB  - Although biochemical properties of 2-Cys peroxiredoxins (Prxs) have been
      extensively studied, their real physiological functions in higher eukaryotic
      cells remain obscure and certainly warrant further study. Here we demonstrated
      that human (h) PrxII, a cytosolic isotype of human 2-Cys Prx, has dual functions
      as a peroxidase and a molecular chaperone, and that these different functions are
      closely associated with its adoption of distinct protein structures. Upon
      exposure to oxidative stress, hPrxII assumes a high molecular weight complex
      structure that has a highly efficient chaperone function. However, the subsequent
      removal of stressors induces the dissociation of this protein structure into low
      molecular weight proteins and triggers a chaperone-to-peroxidase functional
      switch. The formation of a high molecular weight hPrxII complex depends on the
      hyperoxidation of its N-terminal peroxidatic Cys residue as well as on its C
      terminal domain, which contains a "YF motif" that is exclusively found in
      eukaryotic 2-Cys Prxs. A C-terminally truncated hPrxII exists as low and
      oligomeric protein species and does not respond to oxidative stress. Moreover,
      this C-terminal deletion of hPrxII converted it from an oxidation-sensitive to a
      hyperoxidation-resistant form of peroxidase. When functioning as a chaperone,
      hPrxII protects HeLa cells from H(2)O(2)-induced cell death, as measured by a
      terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and
      fluorescence-activated cell sorting analysis.

PMID- 15941720
TI  - The calcium-binding protein S100A2 interacts with p53 and modulates its
      transcriptional activity.
AB  - Head and neck squamous cell carcinoma express high levels of the EF-hand calcium
      binding protein S100A2 in contrast to other tumorigenic tissues and cell lines
      where the expression of this protein is reduced. Subtractive hybridization of
      tumorigenic versus normal tumor-derived mammary epithelial cells has previously
      identified the S100A2 protein as potential tumor suppressor. The biological
      function of S100A2 in carcinogenesis, however, has not been elucidated to date.
      Here, we report for the first time that during recovery from hydroxyurea
      treatment, the S100A2 protein translocated from the cytoplasm to the nucleus and
      co-localized with the tumor suppressor p53 in two different oral carcinoma cells
      (FADU and SCC-25). Co-immunoprecipitation experiments and electrophoretic
      mobility shift assay showed that the interaction between S100A2 and p53 is Ca(2+)
      dependent. Preliminary characterization of this interaction indicated that the
      region in p53 involved with binding to S100A2 is located at the C terminus of
      p53. Finally, luciferase-coupled transactivation assays, where a p53-reporter
      construct was used, indicated that interaction with S100A2 increased p53
      transcriptional activity. Our data suggest that in oral cancer cells the Ca(2+)-
      and cell cycle-dependent p53-S100A2 interaction might modulate proliferation.

PMID- 15941721
TI  - Determination of the functionality of common APOA5 polymorphisms.
AB  - Common variants of APOA5 have consistently shown association with differences in
      plasma triglyceride (TG) levels. These single nucleotide polymorphisms (SNPs)
      fall into three common haplotypes: APOA5*1, with common alleles at all sites;
      APOA5*2, with rare alleles of -1131T--> C, -3A--> G, 751G--> T, and 1891T--> C;
      and APOA5*3, distinguished by the c56C--> G (S19W). Molecular modeling of the
      apoAV signal peptide (SP) showed an increased angle of insertion (65 degrees ) at
      the lipid/water interface of Trp-19 SP compared with Ser-19 SP (40 degrees ),
      predicting reduced translocation. This was confirmed by 50% reduction of Trp-19
      encoded SP.secretory alkaline phosphatase (SEAP) fusion protein secreted into the
      medium from HepG2 cells compared with the Ser-19.SEAP fusion protein (p < 0.002).
      Considering APOA5*2 SNPs, there was no significant difference in the relative
      luciferase expression in Huh7 cells transiently transfected with a -1131T
      construct compared with the -1131C (fragments -1177 to -516 or -1177 to -3).
      Similarly, for the -3A--> G in the Kozak sequence, in vitro
      transcription/translation assays and primer extension inhibition assays showed no
      alternate AUG initiation codon usage, demonstrating that -3A--> G did not
      influence translation efficiency. Although 1891T--> C in the 3'-untranslated
      region disrupts a putative Oct-1 transcription factor binding site, when inserted
      3' of the luciferase gene the T--> C change demonstrated no significant
      difference in luciferase expression. Thus, association of APOA5*2 SNPs with TG
      levels is not due to the individual effects of any of these SNPs, although
      cooperativity between the SNPs cannot be excluded. Alternatively, the effect on
      TG levels may reflect the strong linkage disequilibrium with the functional APOC3
      SNPs.

PMID- 15941722
TI  - Desmoplakin disease in arrhythmogenic right ventricular cardiomyopathy: early
      genotype-phenotype studies.

PMID- 15941723
TI  - Clinical profile of four families with arrhythmogenic right ventricular
      cardiomyopathy caused by dominant desmoplakin mutations.
AB  - AIMS: To characterize the clinical profile of patients belonging to families
      affected with autosomal dominant arrhythmogenic right ventricular cardiomyopathy
      (ARVC) due to mutations of the gene encoding for the cell-to-cell adhesion
      protein desmoplakin (DSP). METHODS AND RESULTS: Thirty-eight subjects belonging
      to four families showing different DSP mutations (three missense and one in the
      intron-exon splicing region) underwent clinical and genetic investigation,
      including annual 12-lead ECG, signal averaged ECG, 24 h Holter ECG, and two
      dimensional echocardiography. Twenty-six family members (11 males and 15 females)
      were found to carry a DSP mutation. After a follow-up of 1-24 years, median 6, 14
      (54%) fulfilled (mean age at diagnosis 33+/-15 years) and 12 (mean age 43+/-24
      years at the last follow-up) did not fulfil the established diagnostic criteria
      of ARVC, although five of them had some cardiac abnormalities. Clinical
      presentations were palpitations in six, sudden death (SD) in three, syncope in
      one, and chest pain with increased myocardial enzymes in two. Abnormal 12-lead
      ECG findings were present in 15 cases (58%), ventricular arrhythmias in 12 (46%),
      and late potentials in 11 (42%). Fourteen (54%) had abnormal echocardiographic
      findings, with left ventricular involvement in seven of them. SD occurred in six
      subjects and in three it was the first symptom of the disease; moreover, one
      subject died due to heart failure. The annual disease-related death and
      SD/aborted SD were 0.028 and 0.023 patient/year, respectively. CONCLUSION:
      Familial ARVC caused by DSP mutations is characterized by a high occurrence of SD
      even as first clinical manifestation. Left ventricular involvement is not a rare
      feature of the disease, which frequently escapes clinical diagnosis by applying
      the currently available criteria. Genetic screening is mandatory for early
      identification of asymptomatic carriers and preventive strategies within a family
      with a genotyped index case.

PMID- 15941724
TI  - Facilitation of primary PCI with ReoPro.

PMID- 15941725
TI  - Androgen excess fetal programming of female reproduction: a developmental
      aetiology for polycystic ovary syndrome?
AB  - The aetiology of polycystic ovary syndrome (PCOS) remains unknown. This familial
      syndrome is prevalent among reproductive-aged women and its inheritance indicates
      a dominant regulatory gene with incomplete penetrance. However, promising
      candidate genes have proven unreliable as markers for the PCOS phenotype. This
      lack of genetic linkage may represent both extreme heterogeneity of PCOS and
      difficulty in establishing a universally accepted PCOS diagnosis. Nevertheless,
      hyperandrogenism is one of the most consistently expressed PCOS traits. Animal
      models that mimic fetal androgen excess may thus provide unique insight into the
      origins of the PCOS syndrome. Many female mammals exposed to androgen excess in
      utero or during early post-natal life typically show masculinized and defeminized
      behaviour, ovulatory dysfunction and virilized genitalia, although behavioural
      and ovulatory dysfunction can coexist without virilized genitalia based upon the
      timing of androgen excess. One animal model shows particular relevance to PCOS:
      the prenatally androgenized female rhesus monkey. Females exposed to androgen
      excess early in gestation exhibit hyperandrogenism, oligomenorrhoea and enlarged,
      polyfollicular ovaries, in addition to LH hypersecretion, impaired embryo
      development, insulin resistance accompanying abdominal obesity, impaired insulin
      response to glucose and hyperlipidaemia. Female monkeys exposed to androgen
      excess late in gestation mimic these programmed changes, except for LH and
      insulin secretion defects. In utero androgen excess may thus variably perturb
      multiple organ system programming and thereby provide a single, fetal origin for
      a heterogeneous adult syndrome.

PMID- 15941726
TI  - Focal myositis with fasciitis and vasculitis revealing chronic lymphocytic
      leukaemia.

PMID- 15941727
TI  - Sacroiliitis presenting as sciatica.

PMID- 15941728
TI  - Fatal Mycobacterium peregrinum pneumonia in refractory polymyositis treated with
      infliximab.

PMID- 15941729
TI  - Coping and psychological adjustment in recent-onset inflammatory polyarthritis:
      the role of gender and age.
AB  - OBJECTIVES: To examine the role of gender, age and coping in psychological
      adjustment of patients with early inflammatory polyarthritis (IP). METHODS: One
      hundred and twelve patients with IP of up to 18 months' duration from the Norfolk
      Arthritis Register completed questionnaires measuring coping, anxiety, disability
      and pain. RESULTS: Thirty-six per cent of the patients were at risk of depressive
      symptoms. Women had significantly higher levels of depression and anxiety than
      men. Regression analyses showed that pain and (low) illness acceptance predicted
      levels of depression. Younger age, wishful thinking and covering up predicted
      anxiety levels. CONCLUSIONS: The study found higher levels of depression and
      anxiety for women than men with early IP. Psychological distress was predicted by
      younger age, specific coping strategies and high levels of pain.

PMID- 15941730
TI  - Interleukin 12 (IL12B), interleukin 12 receptor (IL12RB1) and interleukin 23
      (IL23A) gene polymorphism in systemic lupus erythematosus.
AB  - OBJECTIVE: The aim of this study was to assess the possible association between
      the interleukin-12B (IL12B) and interleukin-12 receptor beta 1 (IL12RB1) gene
      polymorphisms with systemic lupus erythematosus (SLE). In addition, we have
      undertaken a systematic search for genetic variants of interleukin 23 (IL23A).
      METHODS: The study was conducted on 559 SLE patients and 603 ethnically matched
      healthy controls. Genotyping of the IL12B [IL12Bpro and IL12B 3' untranslated
      region (UTR)] and IL12RB1 (641A-->G, 1094T-->C and 1132G-->C) polymorphisms was
      performed with polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and PCR-fluorescent methods, whereas IL23A genetic variants were
      realized with direct sequencing. RESULTS: No statistically significant
      differences in the distribution of the IL12B and the IL12RB1 genotypes and
      alleles were observed when comparing SLE patients and control subjects.
      Additionally, no differences in the genotype and allele distribution were found
      when SLE patients were stratified according to the presence or absence of lupus
      nephritis. Despite an extensive analysis in 30 individuals, variations located in
      the exons and in the 5' and 3' UTR regions of IL23A gene were not found in any
      case. CONCLUSIONS: These results suggest that polymorphisms located in IL12B,
      IL12RB1 and IL23A genes may not play a relevant role in the susceptibility or
      severity of SLE in the Spanish population.

PMID- 15941731
TI  - Undergraduate education in rheumatology.

PMID- 15941732
TI  - Antiretroviral therapy in resource-poor settings: scaling up inequalities?

PMID- 15941733
TI  - The recovery period.

PMID- 15941734
TI  - Moles, weights and potencies: freedom of expression!

PMID- 15941735
TI  - 'Paedfusor' pharmacokinetic data set.

PMID- 15941736
TI  - Massive subcutaneous emphysema after accidental removal of an intercostal drain.

PMID- 15941737
TI  - Confidence with confidence intervals.

PMID- 15941738
TI  - Inter-hospital transfers.

PMID- 15941739
TI  - Difficulty in advancing a tracheal tube over a fibreoptic bronchoscope: more
      solutions.

PMID- 15941741
TI  - Variations in the impact of health coverage expansion proposals across states.
AB  - Most estimates of the consequences of alternative health insurance proposals
      focus on national impact, but the extent of cross-state diversity in uninsurance
      rates, economic and labor-market characteristics, and health care markets
      suggests that the impact of strategies will also vary. We illustrate this
      variation by comparing the effects of standard tax credit and Medicaid expansion
      proposals across states. Some states do well (or poorly) under all policies;
      others benefit under some but not others. Across policies, state effects on
      uninsurance rates vary by at least a factor of 2.5. Uniform national strategies
      that target the uninsured do not generate uniform national outcomes.

PMID- 15941742
TI  - MineBlast: a literature presentation service supporting protein annotation by
      data mining of BLAST results.
AB  - MineBlast is a web service for literature search and presentation based on data
      mining results received from UniProt. Users can submit a simple list of protein
      sequences via a web-based interface. MineBlast performs a BLASTP search in
      UniProt to identify names and synonyms based on homologous proteins and
      subsequently queries PubMed, using combined search terms inorder to find and
      present relevant literature.

PMID- 15941743
TI  - A new progressive-iterative algorithm for multiple structure alignment.
AB  - MOTIVATION: Multiple structure alignments are becoming important tools in many
      aspects of structural bioinformatics. The current explosion in the number of
      available protein structures demands multiple structural alignment algorithms
      with an adequate balance of accuracy and speed, for large scale applications in
      structural genomics, protein structure prediction and protein classification.
      RESULTS: A new multiple structural alignment program, MAMMOTH-mult, is described.
      It is demonstrated that the alignments obtained with the new method are an
      improvement over previous manual or automatic alignments available in several
      widely used databases at all structural levels. Detailed analysis of the
      structural alignments for a few representative cases indicates that MAMMOTH-mult
      delivers biologically meaningful trees and conservation at the sequence and
      structural levels of functional motifs in the alignments. An important
      improvement over previous methods is the reduction in computational cost. Typical
      alignments take only a median time of 5 CPU seconds in a single R12000 processor.
      MAMMOTH-mult is particularly useful for large scale applications. AVAILABILITY:
      http://ub.cbm.uam.es/mammoth/mult.

PMID- 15941744
TI  - Answer to the comments of K. Dobbin, J. Shih and R. Simon on the paper
      'Evaluation of the gene-specific dye-bias in cDNA microarray experiments'.

PMID- 15941745
TI  - Work, retirement and physical activity: cross-sectional analyses from the
      Whitehall II study.
AB  - BACKGROUND: To explore the relationship between work, retirement and physical
      activity. METHODS: Cross-sectional analyses of data from self-completed
      questionnaires by 6224 civil servants aged 45-69 years participating in phase 5
      of the Whitehall II longitudinal study. RESULTS: There appeared to be a dose
      response relationship between hours worked and the prevalence of physical
      activity, with a lower prevalence of recommended physical activity amongst
      participants working full time (> or =30 h/week), higher prevalence rates amongst
      those working part time (<30 h/week), and the highest rates amongst participants
      who were not working at all. Physical activity rates did not increase greatly
      amongst study participants who had retired from the Civil Service but had gone on
      to do further full-time work, however, the higher physical activity rates of
      participants working part time, or not at all, were further enhanced amongst
      those who had also retired. CONCLUSIONS: These findings suggest that full-time
      work is associated with lower rates of recommended physical activity levels in
      this cohort of middle-aged white-collar office workers. Lower grade occupations
      are also less likely to meet the recommended physical activity levels. While
      retirement is associated with higher rates of recommended physical activity
      levels, this benefit is evident amongst those who work part time, or not at all,
      during their retirement, for whom the benefits of retirement and lower working
      hours on rates of physical activity appear additive. The frequency of different
      types of physical activity is associated with different occupational grades, with
      more sport and gardening being done by the higher occupational grades.

PMID- 15941746
TI  - Public understanding of the causes of high stroke risk in northeast Bulgaria.
AB  - BACKGROUND: Knowledge of stroke risk factors is undocumented in Bulgaria.
      METHODS: 188 subjects in 2000 and 447 in 2003 were asked: 'Why do you think
      stroke is so common in this region?' RESULTS: Stress and poverty accounted for
      69% of the first mentions in 2000 and 59% in 2003. There were no mentions of high
      blood pressure and no first mentions of smoking in 2000. High blood pressure
      appears only 10 times and smoking 12 times among 745 answers in 2003. CONCLUSION:
      Health education on the established causes of stroke is an urgent priority in
      Bulgaria.

PMID- 15941747
TI  - Preventing HIV transmission in adolescents: an analysis of the Portuguese data
      from the Health Behaviour School-aged Children study and focus groups.
AB  - BACKGROUND: There is recognition of the need to examine psychosocial and
      ecological determinants contributing to both risk and protective factors related
      to adolescents' sexual behaviour and HIV/AIDS. METHODS: The study utilized mixed
      quantitative and qualitative methods. Data were collected from the Portuguese
      sample of the Health Behaviour in School-aged Children (HBSC) 2002. Based on
      these results, 14 focus group discussions were conducted. RESULTS: A substantial
      minority of young people continue to engage in high-risk practices. Thus, female
      gender, older age, reporting easy to talk with father, not getting drunk and not
      getting involved in fights are significantly associated with protected sexual
      behaviour (using condom during last sexual intercourse). According to these
      results, being female and a comprehensive grade student are both related to a
      significantly more positive attitude towards infected people. It was concluded
      that these adolescents view sexual behaviour, sexual partners and condom use as
      elements within a complex script that governs heterosexual interactions. Several
      themes related to condom used emerged. Despite HIV/AIDS knowledge, young people
      underestimate their own risk of becoming infected with HIV. The majority of
      adolescents believe that HIV-infected people experience discrimination and social
      exclusion. Adolescents' opinions of HIV-infected people were mostly positive.
      Although most participants knew that HIV cannot be transmitted through social
      contact, undefined fears concerning the infection exist. CONCLUSIONS: These
      findings have important implications for the implementation of a comprehensive
      programme on HIV/AIDS education in secondary schools.

PMID- 15941748
TI  - A cohort study to estimate occupational mortality risks in Navarra.
AB  - BACKGROUND: Few studies on occupational mortality have been conducted in Spain.
      The objective of this work was to analyse inequalities on global mortality and on
      mortality due to specific causes according to occupation in a historical cohort
      of males from the province of Navarra, Spain. METHODS: The base population for
      this historical cohort comprised all employed men over age 34 from Navarra in the
      1986 population register. Age-standardised point estimates and confidence
      intervals for occupational-specific mortality risks were computed. RESULTS: There
      exist differences in mortality risks with respect to the overall risk of Navarra
      in certain occupational activities for several major causes of mortality. Some of
      the results corroborate previous findings in other works, such as the significant
      high risk that presents in leather, clothing workers and shoemakers when
      analysing kidney, bladder and other urinary malignant tumours, while others
      present a certain degree of novelty. CONCLUSION: This work contributes to filling
      the gap in the lack of works on occupational mortality in Spain. It also
      complements the information that other monitoring systems may provide on
      occupational health.

PMID- 15941749
TI  - Access to general practitioner services: the disabled elderly lag behind in
      underserved areas.
AB  - BACKGROUND: Several studies have shown that people living in areas underserved in
      physicians have reduced odds of consulting. However, beyond the magnitude of this
      effect averaged for the whole population, policymakers need to know whether
      specific subgroups faced with transportation difficulties, such as the elderly
      and especially the disabled elderly, have a particularly restricted access to
      physicians when residing in underserved areas. METHODS: The study sample,
      representative of the French population aged 18-75 in 1999, comprised 12 405
      individuals. Multilevel Poisson models were used to investigate the impact of the
      area-level density of general practitioners (GPs) on the number of GP
      consultations reported over the previous 12 months. RESULTS: The mean number of
      GP consultations over the previous 12 months was 3.8 (S.D.=4.9). Multivariate
      analyses indicated that living in areas underserved in GPs lead to a greater
      reduction in primary care utilization for the elderly, and especially for the
      disabled elderly, than for younger age groups. The disabled elderly had 244% more
      GP consultations (95% CI:+79%, +562%) when they lived in areas with high versus
      low GP density (defined with the 10th and 90th percentiles as cut-offs).
      CONCLUSION: If further research confirms our findings, this increasingly
      disturbing public health issue in industrialized countries where populations are
      ageing will require priority policy measures. Ensuring that elderly people living
      in underserved areas have adequate access to primary care may prevent future
      hospitalizations, use of home care services and institutionalization.

PMID- 15941750
TI  - Antibiotic prescription in primary health care: clinical and economic
      perspectives (Catalonia, Spain).
AB  - OBJECTIVE: To quantify clinical inappropriateness of antibiotic prescription and
      its costs in primary health care. METHODS: 2470 cases of infectious disease
      during 1998 were analysed. RESULTS: Of all cases, 69.9% did not require
      antibiotic treatment. Global clinical inappropriateness amounted to 43.7%, rising
      to 56.7% with the introduction of economic criteria. Treatment unnecessary but
      antibiotic provided (27.9%) represented the most important category. Costs of
      inappropriateness reached 68.4% of the estimated total cost. CONCLUSION:
      Appropriate antibiotic use should be focused on reducing antibiotic prescription
      when not indicated and restraining the use of penicillins maintaining restrictive
      and adequate health policies, and also achieving co-responsibility from the
      general population.

PMID- 15941753
TI  - Public health genetics--potential for public health?

PMID- 15941751
TI  - Preliminary evaluation of the school-smoking-prevention policy in Greece.

PMID- 15941754
TI  - Global partnerships for health.

PMID- 15941755
TI  - Public health and genetics--a dangerous combination?

PMID- 15941756
TI  - The Belgrade childhood diabetes study: a multivariate analysis of risk
      determinants for diabetes.
AB  - BACKGROUND: The aim of this study was to evaluate some hypotheses about factors
      related to the development of type 1 diabetes mellitus. METHODS: A case-control
      study was conducted in Belgrade during the period 1994-1997. A total of 105
      recently onset diabetic and 210 control children, individually matched by age (+/
      1 year), sex and place of residence, were included in the study. RESULTS:
      According to multivariate regression analysis, the following factors were related
      to type 1 diabetes: stressful events and symptoms of psychological dysfunction
      during the 12 months preceding the onset of the disease [odds ratio (OR) 3.48,
      95% confidence interval (CI) 2.15-5.65; and OR 2.15, 95% CI 1.33-3.48], irregular
      vaccination (OR 16.98, 95% CI 1.38-208.92), infection during 6 months preceding
      the onset of the disease (OR 4.23, 95% CI 1.95-9.17), higher education of father
      (OR 1.50, 95% CI 1.05-2.14), mother's consumption of nitrosoamines-rich food
      during pregnancy (OR 4.33, 95% CI 1.95-9.61), alcohol consumption by father (OR
      3.80, 95% CI 1.64-8.78), insulin-dependent and non-insulin-dependent diabetes
      mellitus in three generations of children's relatives (OR 20.04, 95% CI 4.73
      84.81; and OR 5.52, 95% CI 2.45-12.46), and use of ultrasound diagnostic
      techniques during pregnancy (OR 0.42, 95% CI 0.17-1.00). CONCLUSIONS: Among non
      genetic factors, those affecting the child during pregnancy are especially
      important because of their preventability.

PMID- 15941757
TI  - Environmental tobacco smoke in Norwegian homes, 1995 and 2001: changes in
      children's exposure and parents attitudes and health risk awareness.
AB  - BACKGROUND: The aims of the present study were to assess changes between 1995 and
      2001 in the prevalence of child exposure to environmental tobacco smoke (ETS),
      attitudes towards ETS among parents of small children and awareness among parents
      regarding the potential hazards of passive smoking to children. METHOD: A
      questionnaire, along with a stamped, addressed envelope, was sent to a stratified
      random sample of 1000 households in Norway containing children aged 3 years old
      at the time of the investigation (May 1995 and August 2001). RESULTS: The
      prevalence of households containing smokers was similar in the two study periods.
      However, households reporting exposure of children to ETS fell from 32% in 1995
      to 18% in 2001. Health-risk awareness had significantly increased in households
      containing smokers. In both surveys, the probability of children being exposed to
      ETS was positively correlated with the number of parents smoking, and inversely
      correlated to strength of health-risk awareness, negative attitudes towards ETS
      and length of household education. CONCLUSIONS: Increasing parents' awareness of
      the health risk of ETS exposure to children may significantly reduce children's
      ETS exposure.

PMID- 15941758
TI  - Lack of training as a central barrier to the promotion of smoking cessation: a
      survey among general practitioners in Germany.
AB  - BACKGROUND: General practitioners (GPs) can contribute substantially to the
      promotion of smoking cessation in the general population. However, engagement of
      GPs in helping their patients to quit remains very limited in many countries,
      including Germany. Therefore, new strategies to foster implementation of evidence
      based methods in smoking cessation assistance have to be identified, and data for
      current practice of and barriers against smoking cessation promotion in general
      practice are needed. METHODS: A cross-sectional survey among all 657 general
      practitioners practising in the Rhein-Neckar Region of Germany was conducted in
      spring 2002 using a postal questionnaire (response rate 48%). RESULTS: The
      majority (54%) of GPs reported having treated less than 10 patients for smoking
      cessation (by any means including mere advice to quit) within the last three
      months, 23% of GPs never received any education or training in smoking cessation
      promotion, and only one-third of GPs rated their training as adequate. The factor
      most strongly associated with low activity in smoking cessation promotion
      (defined as having treated less than 10 patients within the last three months)
      was perceived lack of training (odds ratio 2.70, 95% confidence interval 1.68 -
      4.32), followed by perceived lack of demonstration material (2.10, 1.31 - 3.39)
      and perceived lack of time (1.65, 1.02 - 2.66). Furthermore, there was a clear
      dose-response relationship between the time spent on training and the activity in
      smoking cessation promotion. CONCLUSION: Adequate training may be a key factor to
      enhance engagement of general practitioners in the promotion of smoking
      cessation.

PMID- 15941759
TI  - Stages of change and other factors in 'light' cigarette smokers.
AB  - BACKGROUND: It has become well known that 'light' cigarettes are deceiving in
      fostering the attitude that they are 'safer' or less health damaging than regular
      cigarettes. The goal of this study is to analyse the smoking of 'light'
      cigarettes according to the progress over the stages of change to stop or reduce
      smoking. METHODS: A sample representing the general population of a northern
      German region aged 18 to 64 was drawn (T1, N=4075). 1520 smokers of 'light' and
      regular cigarettes were identified by a face-to-face interview and reassessed
      longitudinally by questionnaire 30 months later (T2, n=913). RESULTS: At baseline
      smokers of 'light' cigarettes, in particular males, were more likely to be
      contemplators or preparators in terms of smoking cessation. Those who smoked
      'light' cigarettes were more likely to have made a quit attempt, were more likely
      to be female, at younger age, never married, higher educated and less nicotine
      dependent compared to smokers of regular cigarettes. The follow-up data shows
      that males who smoked 'light' before or changed to 'light' cigarettes were more
      likely to contemplate or to prepare quitting, had more often tried a quit attempt
      and stopped smoking more often. CONCLUSION: The results suggest that 'light'
      cigarettes especially by males are used for reasons of reducing or quitting
      smoking. It is concluded that as such they deceive the smoker and potentially
      hinder the process of reducing or quitting.

PMID- 15941760
TI  - Correlates of stages of change of smoking among inhabitants of deprived
      neighbourhoods.
AB  - BACKGROUND: This study examines the prevalence and correlates of stages of change
      of smoking, in terms of psychosocial, structural and sociodemographic factors,
      among inhabitants of deprived neighbourhoods. METHODS: Cross-sectional data were
      obtained from a survey on health related behaviour. Subjects were 2009 current
      and former smokers, aged 20-46, living in deprived neighbourhoods in Rotterdam,
      the second largest city in the Netherlands. Three groups of smokers were formed
      according to the stages of change-definitions of the Transtheoretical Model:
      smokers not planning to quit (precontemplators), smokers planning to quit
      (contemplators/preparators) and former smokers (actors/maintainers). Smokers
      planning to quit and smokers not planning to quit were compared regarding
      psychosocial factors (attitude, social norm, self-efficacy), structural factors
      (neighbourhood problems, material deprivation, financial problems, employment
      status) and sociodemographic factors (age, gender, marital status, cultural
      background, educational level). Former smokers were compared with smokers
      planning to quit regarding structural and sociodemographic factors. Logistic
      regression was used to assess correlates of stages of change. RESULTS: Smokers
      planning to quit (prevalence = 19%) reported a more positive attitude, stronger
      social norms and higher self-efficacy expectations in quitting smoking than
      smokers not planning to quit (prevalence = 57%). Smokers planning to quit less
      often were Dutch-born, more often had attended higher vocational schooling or
      university and more often reported experiencing two or more neighbourhood
      problems compared to smokers not planning to quit. Former smokers (prevalence =
      24%) were older, more often Dutch-born, married, employed and higher educated,
      compared to smokers planning to quit. Furthermore, former smokers less often
      reported material deprivation and financial problems than smokers planning to
      quit. CONCLUSION: Among people living in deprived neighbourhoods, different
      factors correlate with different stages of change of smoking. Implications for
      health promotion are discussed.

PMID- 15941761
TI  - Smoking habit, respiratory symptoms and lung function in young adults.
AB  - BACKGROUND: Smoking is the primary cause of deterioration in forced expiratory
      volume (FEV(1)) and the development of chronic obstructive lung disease. This
      study assessed the independent association of smoking with respiratory symptoms
      and lung function in young adults who took part in the European Community
      Respiratory Health Survey (ECRHS-I). METHODS: Cross-sectional multi-centre survey
      of a general population of young adults aged 20(44 years in the ECRHS(I conducted
      in five Spanish centres. Several groups were created in an exclusive and
      descendent manner from the subjects who completed the questionnaire in accordance
      with how they had answered the questions: asthma-related symptoms; chronic
      bronchitis symptoms; minor respiratory symptoms; chronic cough; and no
      respiratory symptoms. Among a subset of the population, forced spirometry tests
      were performed. Linear and logistical regression models were used to assess the
      relationship of smoking in the presence of symptoms and its impact on lung
      function, adjusted by other important variables. RESULTS: The prevalence of
      respiratory symptoms was higher among smokers. After adjusting for geographical
      area, total IgE, age, sex, and FEV(1), smoking was associated with an increased
      risk of chronic bronchitis and other respiratory symptoms. These risks increased
      with increasing number of cigarettes smoked per day. A deterioration of FEV(1)
      and the FEV(1)/FVC ratio was also directly associated with the number of
      cigarettes smoked per day. CONCLUSION: Even among young adults, smoking confers a
      high risk of developing a number of respiratory symptoms and the deterioration of
      the ventilatory function.

PMID- 15941762
TI  - Mothers and daughters: intergenerational patterns of reproduction.
AB  - BACKGROUND: The objective of this study was to assess intergenerational mother
      daughter patterns of reproduction. METHODS: In 1966, 12 055 pregnant women in
      Northern Finland, representing 96% of all births in the region, responded to a
      questionnaire in mid-gestation. In 1997-98, the 31-year-old daughters born from
      those pregnancies were sent a questionnaire and 4523 (80%) responded.
      Reproduction was compared between all mother-daughter pairs (n=4523) and
      separately for the pairs (n=489) of similar age (mothers 30-32 years). RESULTS:
      The menarcheal ages of the mothers and their daughters correlated slightly
      (Spearman correlation coefficient 0.206). The probability of the daughter to be
      multiparous was higher if her mother was multiparous at the time of the
      daughter's birth than if she was not. No association in the rate of spontaneous
      abortions was found. The first pregnancy of the daughters born from unwanted
      pregnancies was more often unwanted than the first pregnancy of the wanted
      daughters, after adjusting for parity (P=0.004). The analysis of the age-matched
      mother-daughter pairs gave similar results. CONCLUSION: A positive association
      between mothers and daughters in menarcheal age, parity and desirability of
      pregnancy was found.

PMID- 15941763
TI  - How is your health in general? A qualitative study on self-assessed health.
AB  - BACKGROUND: The single-item measure on self-assessed health has been widely used,
      as it presents researchers with a summary of an individual's general state of
      health. A qualitative study was initiated to find out which particular aspects
      are included in health self-assessments; which aspects do people consider when
      answering the question 'How is your health in general?'. Subgroup differences
      were studied with respect to gender, age, health status and health assessment.
      METHODS: Qualitative study with stratification by background characteristic,
      health status and health assessment (n=40). RESULTS: Almost 80% of the
      participants referred to one or more physical aspects (chronic illness, physical
      problems, medical treatment, age-related complaints, prognosis, bodily mechanics,
      and resilience). However, when assessing their health, participants also include
      aspects that go beyond the physical dimension of health. In total, 80 percent of
      the participants-whether or not in addition to physical aspects-referred to other
      health dimensions. Besides physical aspects, participants considered the extent
      to which they are able to perform (functional dimension -28%), the extent to
      which they adapted to, or their attitude towards an existing illness (coping
      dimension -28%), and simply the way they feel (wellbeing dimension -20%). In this
      study, health behaviour or lifestyle factors (behavioural dimension -3%) proved
      to be relatively unimportant in health self-assessments. CONCLUSIONS: Self
      assessed health proved to be a multidimensional concept. For most part, subgroup
      differences in self-assessed health could be attributed to experience with ill
      health: being relatively inexperienced with health problems versus having a
      history of health problems.

PMID- 15941764
TI  - Total workload, work stress and perceived symptoms in Swedish male and female
      white-collar employees.
AB  - BACKGROUND: The aim of this study was to analyse how paid work, unpaid household
      tasks, child care, work-child care interactions and perceived work stress are
      associated with reported symptoms in male and female white-collar employees.
      METHODS: A questionnaire was mailed to 1300 men and 1300 women belonging to the
      white-collar sector, with at least 35 hours of regular employment a week and a
      participant age of between 32 and 58 years. It contained items relating to total
      workload (hours spent on paid work, unpaid household tasks and childcare),
      subjective indices for work stress and symptoms. The response rate was 65% (743
      women; 595 men). Gender difference in symptom prevalence was tested by analyses
      of variance. Odds ratios were used to estimate the bivariate associations between
      work-related variables and symptom prevalence. A multivariate analysis estimated
      the effect of paid and unpaid work interaction, work-childcare interplay and
      possible synergy. RESULTS: The frequency and severity of symptoms was higher in
      women than in men (P < 0.0001). Employed women's health was determined by the
      interaction between conditions at work and household duties (OR 2.09; 1.06-4.14),
      whereas men responded more selectively to long working hours, i.e. >50 h/week (OR
      1.61; 1.02-2.54). However, childcare (<21 h/week) appeared to have a buffer
      effect on the risk of a high level of symptoms in men working long hours.
      CONCLUSION: Working life and private circumstances and the interplay between them
      need to be taken into account to curb stress-related ill health in both men and
      women.

PMID- 15941765
TI  - On the use of administrative databases to support planning activities: a comment.

PMID- 15941767
TI  - BimEL up-regulation potentiates AIF translocation and cell death in response to
      MPTP.
AB  - This study attempted to elucidate the signaling mechanism underlying dopaminergic
      cell death in the MPP+ model for Parkinson's disease. In neuronal-differentiated
      PC12 cells, through the regulation by activated JNK and c-jun, BimEL expression
      was markedly increased in response to MPP+ treatment, which led to the cell
      degeneration. In lieu of Smac translocation as seen in other paradigms, up
      regulation of BimEL effected an increase in calpain I activity that, in turn,
      mediated AIF release from the mitochondria. In support, we found that knocking
      down BimEL expression resulted in a decrease in calpain I activity, as well as
      AIF release from the mitochondria and cell death. Finally, inhibition of calpain
      activity mitigated AIF release from the mitochondria and cell death. Under cell
      free conditions, activated purified calpain I could induce the release of AIF
      from isolated mitochondria without the participation of BimEL or activated JNK,
      suggesting that AIF release is a direct consequence of calpain I activity. In
      concert, the results suggest a novel signaling pathway for dopaminergic cell
      degeneration, in which MPP+ induces the up-regulation of BimEL, which in turn
      potentiates an elevation in calpain I activity that mediates AIF release and cell
      death in a caspase-independent manner.

PMID- 15941768
TI  - Activation of the endocannabinoid system as therapeutic approach in a murine
      model of multiple sclerosis.
AB  - Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD)
      is a well-characterized murine model of human multiple sclerosis (MS) that
      closely resembles the chronic and progressive clinical form of the disease.
      Recent studies have described the involvement of the cannabinoid system in the
      progression of the disease and the benefits associated with the administration of
      cannabinoid agonists. With the objective to study whether "indirect" agonists,
      that is, compounds able to reinforce the physiological endocannabinoid
      transmission and, therefore, devoid of the psychotropic effects of "direct"
      agonists, could be suitable agents for the amelioration of MS neurological
      deficits, we administered the potent and selective anandamide uptake inhibitor
      UCM707 to TMEV-infected mice. Our results indicate that treatment during
      established disease significantly improves the motor function of the diseased
      mice. At the histological level, UCM707 is able to reduce microglial activation,
      diminish major histocompatibility complex class II antigen expression, and
      decrease cellular infiltrates in the spinal cord. Additionally, in microglial
      cells, UCM707 decreases the production of the proinflammatory cytokines tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6; reduces nitric
      oxide levels and inducible nitric oxide synthase expression; and is able to
      potentiate the action of a subeffective dose of the endocannabinoid anandamide.
      Overall, these results suggest that agents able to activate the endocannabinoid
      system could constitute a new series of drugs for the treatment of MS.

PMID- 15941769
TI  - Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing
      pathway.
AB  - Hypoxia-inducible transcription factor (HIF) is regulated by two oxygen-dependent
      events that are catalyzed by the HIF prolyl 4-hydroxylases (HIF-P4Hs) and HIF
      asparaginyl hydroxylase (FIH). We have purified the three recombinant human HIF
      P4Hs to near homogeneity and characterized their catalytic properties and
      inhibition and those of FIH. The specific activities of the HIF-P4Hs were at
      least 40-50 mol/mol/min, and they and FIH catalyzed an uncoupled decarboxylation
      of 2-oxoglutarate in the absence of any peptide substrate. The purified HIF-P4Hs
      showed considerable activities even without added Fe2+, their apparent Km values
      for iron being markedly lower than that of FIH. Desferrioxamine and several
      metals were effective inhibitors of FIH, but surprisingly, ineffective inhibitors
      of the HIF-P4Hs in vitro, especially of HIF-P4H-2. Desferrioxamine and cobalt
      were more effective in cultured insect cells synthesizing recombinant HIF-P4H-2,
      but complete inhibition was not achieved and most of the enzyme was inactivated
      irreversibly. Cobalt also rapidly inactivated HIF-P4Hs during storage at 4
      degrees C. The well-known stabilization of HIF-alpha by cobalt and nickel is thus
      not due to a simple competitive inhibition of HIF-P4Hs. The effective inhibition
      of FIH by these metals and zinc probably leads to full transcriptional activity
      of HIF-alpha even in concentrations that produce no stabilization of HIF-alpha.

PMID- 15941770
TI  - Patterns of physical activity determined by heart rate monitoring among diabetic
      children.
AB  - BACKGROUND: Children with type 1 diabetes should be encouraged to participate in
      physical activity because exercise can benefit insulin sensitivity and improve
      known risk factors for atherosclerosis. METHODS: Physical activity patterns of
      127 children and adolescents with stable type 1 diabetes were investigated by 24
      hour continuous heart rate monitoring. The percentage of heart rate reserve was
      used to measure the amounts of physical activity at different intensities. The
      results were compared with normative data. RESULTS: Diabetic preschoolchildren
      accumulated 192.7 (78.1), 39.1 (24.3), and 21.3 (9.4) minutes/day (mean (SD)) of
      light, moderate, and vigorous physical activity, respectively. At the same
      activity levels, diabetic schoolchildren accumulated 168.9 (76.7), 37.9 (15.9),
      and 19.0 (14.8) minutes/day, and diabetic teenagers accumulated 166.3 (67.5),
      45.6 (26.9), and 25.2 (15.3) minutes/day. Diabetic schoolchildren were
      significantly more active than healthy peers when considering moderate activity;
      diabetic teenagers were significantly more active when considering moderate and
      vigorous activity. There was a negative correlation between the most recent
      glycated haemoglobin and the time spent in light activities in schoolchildren,
      and a negative correlation between mean glycated haemoglobin for one year and
      time spent in light and moderate activities in schoolchildren. CONCLUSION: The
      majority of our diabetic patients meet the classical paediatric guidelines for
      physical activity and compare favourably with their healthy peers.

PMID- 15941771
TI  - Diabetes services in the UK: fourth national survey; are we meeting NSF standards
      and NICE guidelines?
AB  - BACKGROUND: Previous surveys of children's diabetes service provision in the UK
      have shown gradual improvements but continuing deficiencies. AIM: To determine
      whether further improvements in services have occurred. METHODS: A questionnaire
      was mailed to all paediatricians in the UK identified as providing care for
      children and adolescents with diabetes. Responses were compared with results of
      three previous surveys, and with recommendations in the Diabetes NSF and the NICE
      type 1 diabetes guidelines. RESULTS: Replies were received from 187 consultant
      paediatricians in 169 centres looking after children; 89% expressed a special
      interest in diabetes, 98% saw children in a designated diabetic clinic, and 95%
      clinics now have more than 40 patients. In 98% of the clinics there was a
      specialist nurse (82% now children's trained), but 61% clinics had a
      nurse:patient ratio <1:100; 39% of clinics did not have a paediatric dietician
      and in 78% there was no access to psychology/psychiatry services in clinics.
      Glycated haemoglobin was measured routinely at clinics in 86%, annual screening
      for retinopathy performed in 80%, and microalbuminuria in 83%. All centres now
      have local protocols for ketoacidosis, but not for children undergoing surgery
      (90%) or severe hypoglycaemia (74%). Mean clinic HbA1c levels were significantly
      lower in the clinics run by specialists (8.9%) than generalists (9.4%). There
      have been incremental improvements over the last 14 years since the surveys
      began, but only two clinics met all the 10 previously published recommendations
      on standards of care. CONCLUSIONS: The survey shows continuing improvements in
      organisational structure of services for children with diabetes but serious
      deficiencies remain. Publication and dissemination of the results of the previous
      surveys may have been associated with these improvements and similar recurrent
      service review may be applicable to services for other chronic childhood
      conditions.

PMID- 15941772
TI  - Evaluation of the WHO clinical decision rule for streptococcal pharyngitis.
AB  - AIMS: To prospectively assess the WHO clinical decision rule (CDR) for group A
      beta haemolytic streptococcal (GABHS) pharyngitis in three countries. METHODS: A
      prospective, observational cohort study in urban outpatient clinics in Rio de
      Janeiro, Cairo, and Zagreb. There were 2225 children aged 2-12 years with cough,
      rhinorrhoea, red or sore throat; 1810 of these with sore throat were included in
      the analysis. RESULTS: The proportion of children presenting with sore throat and
      found to have GABHS pharyngitis ranged from 24.6% (Brazil) to 42.0% (Croatia).
      WHO CDR sensitivity was low for all sites in both age groups. In children age 5
      or older, sensitivity ranged from 3.8% in Egypt to 10.8% in Brazil. In children
      under 5, sensitivity was low (0.0-4.6%) Specificity was high in both age groups
      in all countries (93.8-97.4%). CONCLUSIONS: In these populations, the current WHO
      CDR has high specificity, but low sensitivity; it did not detect up to 96.0% of
      children who have laboratory confirmed GABHS pharyngitis. A CDR with higher
      sensitivity should be developed for use in regions where rheumatic fever and
      rheumatic heart disease are still major health problems.

PMID- 15941773
TI  - Success with hydrostatic reduction of intussusception in relation to duration of
      symptoms.
AB  - BACKGROUND: It is widely believed that hydrostatic reduction of intussusception
      is less successful in children with prolonged symptoms prior to presentation.
      AIM: To prospectively evaluate success in relation to duration of symptoms.
      METHODS: Prospective study in which children, regardless of symptom duration,
      underwent an attempt at hydrostatic reduction. RESULTS: Of 113 children
      presenting with intussusception, 16 had peritonitis and required immediate
      laparotomy. A hydrostatic reduction was attempted in 97 and was successful in 77
      (79%). There were 26 successful reductions with symptoms <12 hours (81%), 30 with
      symptoms for 12-24 hours (81%), and 21 with symptoms >24 hours (75%). CONCLUSION:
      The success rate with hydrostatic reduction was not significantly influenced by
      symptom duration.

PMID- 15941774
TI  - The antibacterial activity of honey against coagulase-negative staphylococci.
AB  - OBJECTIVES: Development of antibiotic-resistant strains of coagulase-negative
      staphylococci has complicated the management of infections associated with the
      use of invasive medical devices, and innovative treatment and prophylactic
      options are needed. Honey is increasingly being used to treat infected wounds,
      but little is known about its effectiveness against coagulase-negative
      staphylococci. The aim of this study was to determine the minimum active dilution
      of two standardized, representative honeys for 18 clinical isolates of coagulase
      negative staphylococci. METHODS: An agar incorporation technique was used to
      determine the minimum active dilution, with dilution steps of 1% (v/v) honey [or
      steps of 5% (v/v) of a sugar syrup matching the osmotic effect of honey]. The
      plates were inoculated with 10 microL spots of cultures of the isolates. RESULTS:
      The honeys were inhibitory at dilutions down to 3.6 +/- 0.7% (v/v) for the
      pasture honey, 3.4 +/- 0.5% (v/v) for the manuka honey and 29.9 +/- 1.9% (v/v)
      for the sugar syrup. CONCLUSIONS: Typical honeys are about eight times more
      potent against coagulase-negative staphylococci than if bacterial inhibition were
      due to their osmolarity alone. Therefore, honey applied to skin at the insertion
      points of medical devices may have a role in the treatment or prevention of
      infections by coagulase-negative staphylococci.

PMID- 15941775
TI  - beta-Lactamases among extended-spectrum beta-lactamase (ESBL)-resistant
      Salmonella from poultry, poultry products and human patients in The Netherlands.
AB  - OBJECTIVES: The purpose of this work was to study the genetic determinants
      responsible for extended-spectrum beta-lactamase (ESBL) resistance of Salmonella
      isolated from Dutch poultry, poultry meat and hospitalized humans. METHODS:
      Thirty-four ESBL-resistant Salmonella isolates from The Netherlands were tested
      towards 21 antimicrobial agents. PCR and sequencing were used to determine the
      underlying genetic determinants responsible for the ESBL phenotypes. The
      transferability of the ESBL phenotypes was tested by conjugation to a susceptible
      Salmonella enterica serovar Dublin and plasmid purification, restriction fragment
      length polymorphism (RFLP) and pulsed-field gel electrophoresis (PFGE) were
      employed to further characterize a subset of the isolates. RESULTS: A great
      genetic diversity was seen among the isolates. The bla(TEM-52) gene was most
      predominant and was found among Salmonella enterica serovars Blockley, Thomson,
      London, Enteritidis phage type 14b, Paratyphi B, Virchow and Typhimurium phage
      types 11 and 507. We also found the bla(TEM-20) gene in S. Paratyphi B var. Java
      and the bla(TEM-63) gene in S. Isangi. Furthermore, we detected the bla(CTX-M-28)
      gene in S. Isangi and the bla(CTX-M-3) gene in S. Typhimurium phage type 507. The
      bla(CTX-M-2) gene was identified in S. Virchow, which also contained a copy of
      the bla(SHV-2) gene and a copy of the bla(TEM-1) gene. The bla(SHV-12) gene was
      found alone in S. Concord and together with the bla(TEM-52) gene in S.
      Typhimurium. Finally, the bla(ACC-1) gene was cloned from a S. Bareilly isolate
      and was found to be present on indistinguishable plasmids in all S. Bareilly
      isolates examined as well as in a S. Braenderup isolate and a S. Infantis
      isolate. CONCLUSIONS: Our data underscore the diversity of ESBL genes in
      Salmonella enterica isolated from animals, food products and human patients.

PMID- 15941776
TI  - Antibacterial activities of gemifloxacin, levofloxacin, gatifloxacin,
      moxifloxacin and erythromycin against intracellular Legionella pneumophila and
      Legionella micdadei in human monocytes.
AB  - OBJECTIVES: The antibacterial activity of a new fluoroquinolone, gemifloxacin,
      was tested against intracellular Legionella pneumophila and Legionella micdadei
      and was compared with the activities of levofloxacin, gatifloxacin, moxifloxacin
      and erythromycin. METHODS: For intracellular assays, bacteria were used to infect
      human monocyte-derived macrophages prepared from heparinized blood of healthy
      volunteers. Antibiotics were added following phagocytosis. Numbers of viable
      bacteria were determined at 0, 24, 48, 72 and 96 h. RESULTS: The intracellular
      antibacterial activity of gemifloxacin was concentration- and time-dependent. All
      of the quinolones had similar activities against L. pneumophila and L. micdadei
      at 10 x MIC, but there were minor differences: at 24 h moxifloxacin was
      significantly more active than the other quinolones against L. pneumophila, while
      gemifloxacin was more active against L. micdadei (P < 0.01). All of the
      quinolones were markedly more active than erythromycin (P < 0.01). The
      antibacterial effect of gemifloxacin against L. pneumophila following drug
      removal at 24 h persisted for 72 h at 20 x MIC but not at 10 x MIC, while for L.
      micdadei the antibacterial effect persisted for 24 h at 10 x MIC. CONCLUSIONS:
      All of the quinolones had similar activities against intracellular L. pneumophila
      and L. micdadei and were markedly more effective than erythromycin.

PMID- 15941777
TI  - The management of HIV-1 protease inhibitor pharmacokinetic interactions.
AB  - The HIV-1 protease inhibitors (PIs) are widely used in combination antiretroviral
      therapy for the management of HIV-1 infection. Certain characteristics of the
      PIs, in particular their metabolism being mainly via the cytochrome P450
      isoenzyme group and their gastric absorption being pH dependent, make them prone
      to clinically significant drug interactions with other antiretrovirals,
      concomitant medication and complementary treatments. Owing to the nature of the
      disease, individuals with HIV are frequently prescribed complex treatment
      regimens (both for the management of intolerance, toxicity and viral resistance
      to antiretroviral therapy, and in the management of co-morbid states) that may
      interact with PI therapy. For many of these potential interactions, few data are
      available. This review will focus on the current use of PIs, highlighting some
      important management issues encountered with common pharmacokinetic interactions
      seen in clinical practice.

PMID- 15941778
TI  - CD14 deficiency leads to increased MIP-2 production, CXCR2 expression, neutrophil
      transmigration, and early death in pneumococcal infection.
AB  - CD14 is a myeloid receptor for bacterial cell membrane/wall components, for which
      we previously showed a strong induction in cerebrospinal fluid (CSF) during
      meningitis. Here, we studied CD14 function in murine Streptococcus pneumoniae
      meningitis by using wild-type (WT), CD14(-/-) mice, and WT mice pretreated with
      neutralizing anti-CD14 antibodies. Early polymorphonuclear leukocytes (PMN)
      immigration was more pronounced in CSF of CD14(-/-) than of WT mice. This was not
      a result of altered adherence molecule expression in blood and CSF PMN or brain
      endothelial cells. Macrophage inflammatory protein-2 (MIP-2) and keratinocyte
      derived chemokine levels were similar in CSF in both strains, but MIP-2 was
      higher in infected brain and in brain-derived endothelial cells infected in vitro
      in CD14(-/-) than in WT mice. CD14(-/-) PMN demonstrated increased expression of
      CXC chemokine receptor 2 (CXCR2) after infection and stronger in vitro chemotaxis
      than WT PMN toward CSF from WT or CD14(-/-) mice and toward MIP-2. Excess PMN
      migration in CD14(-/-) mice did not result in improved bacterial clearing but in
      increased tumor necrosis factor in CSF, higher disease severity, and earlier
      death. Pretreatment with anti-CXCR2 reduced PMN infiltration into CSF and brain
      MIP-2 production and abolished earlier mortality in CD14(-/-) mice. In
      conclusion, CD14 plays a protective role in pneumococcal meningitis by slowing
      PMN migration via MIP-2 and CXCR2 modulation.

PMID- 15941779
TI  - Highly glycosylated alpha1-acid glycoprotein is synthesized in myelocytes, stored
      in secondary granules, and released by activated neutrophils.
AB  - Alpha-1-acid glycoprotein (AGP) is an acute-phase protein produced by hepatocytes
      and secreted into plasma in response to infection/injury. We recently assessed
      the transcriptional program of terminal granulocytic differentiation by
      microarray analysis of bone marrow (BM) populations highly enriched in
      promyelocytes, myelocytes/metamyelocytes (MYs), and BM neutrophils. These
      analyses demonstrated a transient, high mRNA expression of genuine
      secondary/tertiary granule proteins and AGP in MYs. In agreement with this,
      immunocytochemistry revealed the presence of AGP protein and the secondary
      granule protein lactoferrin in cells from the MY stage and throughout
      granulocytic differentiation. Immunoelectron microscopy demonstrated the
      colocalization of AGP and lactoferrin in secondary granules of neutrophils. This
      finding was substantiated by the failure to detect AGP and lactoferrin in blood
      cells from a patient with secondary/tertiary (specific) granule deficiency. In
      addition, Western blot analysis of subcellular fractions isolated from
      neutrophils revealed that neutrophil-derived AGP, localized in secondary
      granules, was abundant and highly glycosylated compared with endocytosed, plasma
      derived AGP localized in secretory vesicles. Exocytosis studies further
      demonstrated a marked release of AGP and lactoferrin by activated neutrophils.
      Finally, induction of CCAAT/enhancer-binding protein (C/EBP)-epsilon in a myeloid
      cell line was shown to increase AGP transcript levels, indicating that AGP
      expression in myeloid cells, like in hepatocytes, is partially regulated by
      members of the C/EBP family. Overall, these findings define AGP as a genuine
      secondary granule protein of neutrophils. Hence, neutrophils, which constitute
      the first line of defense, are likely to serve as the primary local source of AGP
      at sites of infection or injury.

PMID- 15941780
TI  - Cardiac and renal antioxidant enzymes and effects of tempol in hyperthyroid rats.
AB  - This study evaluated the activity of cardiac and renal antioxidant enzymes
      [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and
      glutathione reductase (GR)] and whether chronic treatment with tempol, a cell
      membrane-permeable SOD mimetic, ameliorates the hypertension of hyperthyroidism.
      Two experiments were performed. In experiment I, the following four groups of
      male Wistar rats were used: control group and three groups that received
      thyroxine (T4) at 10, 50, or 75 microg x rat(-1) x day(-1). In experiment II,
      tempol was orally administered (18 mg x kg(-1) x day(-1)) to control and T4
      treated (75 microg x rat(-1) x day(-1)) rats. All treatments were maintained for
      6 wk. Body weight, tail systolic blood pressure (BP), and heart rate were
      measured one time a week, and direct BP and morphological, metabolic, plasma, and
      renal variables were measured at the end of the experiment. Enzymatic activities
      were measured in renal cortex and medulla and right and left ventricles. In renal
      cortex, SOD activity was decreased in the T4-75 group, and there was a dose
      related increase in CAT activity and decrease in GPX and GR activities in T4
      treated groups. Activity of all antioxidant enzymes was reduced in left ventricle
      in T4-50 and T4-75 groups and in right ventricle in the T4-75 group. Tempol
      reduced BP, plasma malondialdehyde, and total urinary excretion of F2
      isoprostanes in hypertensive hyperthyroid rats but not in controls. Tempol did
      not improve cardiac hypertrophy, proteinuria, or creatinine clearance in
      hyperthyroid rats. In conclusion, the results obtained indicate that the activity
      of SOD, GPX, and GR in renal and cardiac tissues is decreased in hyperthyroidism
      and that antioxidant treatment with tempol ameliorates T4-induced hypertension.

PMID- 15941781
TI  - Weight loss increases cardiovagal baroreflex function in obese young and older
      men.
AB  - We tested the hypothesis that reductions in total body and abdominal visceral fat
      with energy restriction would be associated with increases in cardiovagal
      baroreflex sensitivity (BRS) in overweight/obese older men. To address this,
      overweight/obese (25 < or = body mass index < or = 35 kg/m(2)) young (OB-Y, n =
      10, age = 32.9 +/- 2.3 yr) and older (OB-O, n = 6, age = 60 +/- 2.7 yr) men
      underwent 3 mo of energy restriction at a level designed to reduce body weight by
      5-10%. Cardiovagal BRS (modified Oxford technique), body composition (dual-energy
      X-ray absorptiometry), and abdominal fat distribution (computed tomography) were
      measured in the overweight/obese men before weight loss and after 4 wk of weight
      stability at their reduced weight and compared with a group of nonobese young men
      (NO-Y, n = 13, age = 21.1 +/- 1.0 yr). Before weight loss, cardiovagal BRS was
      approximately 35% and approximately 60% lower (P < 0.05) in the OB-Y and OB-O
      compared with NO-Y. Body weight (-7.8 +/- 1.1 vs. -7.3 +/- 0.7 kg), total fat
      mass (-4.1 +/- 1.0 vs. -4.4 +/- 0.8 kg), and abdominal visceral fat (-27.6 +/-
      6.9 vs. -43.5 +/- 10.1 cm(2)) were reduced (all P < 0.05) after weight loss, but
      the magnitude of reduction did not differ (all P > 0.05) between OB-Y and OB-O,
      respectively. Cardiovagal BRS increased (11.5 +/- 1.9 vs. 18.5 +/- 2.6 ms/mmHg
      and 6.7 +/- 1.2 vs. 12.8 +/- 4.2 ms/mmHg) after weight loss (both P < 0.05) in OB
      Y and OB-O, respectively. After weight loss, cardiovagal BRS in the
      obese/overweight young and older men was approximately 105% and approximately 73%
      (P > 0.05) of NO-Y (17.5 +/- 2.2 ms/mmHg). Therefore, the results of this study
      indicate that weight loss increases the sensitivity of the cardiovagal baroreflex
      in overweight/obese young and older men.

PMID- 15941782
TI  - Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937
      histiocytes by enhancing AP-1 and NF-kappaB transcriptional activities.
AB  - The plasma lactate concentration in patients with obesity and type 2 diabetes is
      often higher than that in nondiabetic individuals. Although it is known that
      increased lactate concentration is an independent risk factor for developing type
      2 diabetes, the underlying mechanisms are not well understood. Because
      inflammation plays an important role in the development of type 2 diabetes, we
      postulated that increased lactate level might contribute to the pathogenesis of
      type 2 diabetes by enhancing inflammation. In the present study, we demonstrated
      that preexposure of U937 macrophage-like cells to sodium lactate increased LPS
      stimulated matrix metalloproteinase (MMP)-1, IL-1beta, and IL-6 secretion.
      Augmentation of LPS-stimulated MMP-1 secretion was diminished when sodium lactate
      was replaced by lactic acid that reduced pH in the culture medium. Furthermore,
      quantitative real-time PCR indicated that the increased secretion of MMP-1, IL
      1beta, and IL-6 was due to increased mRNA expression. To explore the underlying
      signaling mechanism, blocking studies using specific inhibitors for NF-kappaB and
      MAPK cascades were performed. Results showed that blocking of either NF-kappaB or
      MAPK pathways led to the inhibition of MMP-1, IL-1beta, and IL-6 expression
      stimulated by sodium lactate, LPS, or both. Finally, electrophoretic mobility
      shift assays showed a synergy between sodium lactate and LPS on AP-1 and NF
      kappaB transcriptional activities. In conclusion, this study has demonstrated for
      the first time that sodium lactate and LPS exert synergistic effect on MMP and
      cytokine expression through NF-kappaB and MAPK pathways and revealed a novel
      mechanism potentially involved in the development of type 2 diabetes and its
      complications.

PMID- 15941783
TI  - Differential effects of pharmacological liver X receptor activation on hepatic
      and peripheral insulin sensitivity in lean and ob/ob mice.
AB  - Liver X receptor (LXR) agonists have been proposed to act as anti-diabetic drugs.
      However, pharmacological LXR activation leads to severe hepatic steatosis, a
      condition usually associated with insulin resistance and type 2 diabetes
      mellitus. To address this apparent contradiction, lean and ob/ob mice were
      treated with the LXR agonist GW-3965 for 10 days. Insulin sensitivity was
      assessed by hyperinsulinemic-euglycemic clamp studies. Hepatic glucose production
      (HGP) and metabolic clearance rate (MCR) of glucose were determined with stable
      isotope techniques. Blood glucose and hepatic and whole body insulin sensitivity
      remained unaffected upon treatment in lean mice, despite increased hepatic
      triglyceride contents (61.7 +/- 7.2 vs. 12.1 +/- 2.0 nmol/mg liver, P < 0.05). In
      ob/ob mice, LXR activation resulted in lower blood glucose levels and
      significantly improved whole body insulin sensitivity. GW-3965 treatment did not
      affect HGP under normo- and hyperinsulinemic conditions, despite increased
      hepatic triglyceride contents (221 +/- 13 vs. 176 +/- 19 nmol/mg liver, P <
      0.05). Clamped MCR increased upon GW-3965 treatment (18.2 +/- 1.0 vs. 14.3 +/-
      1.4 ml x kg(-1) x min(-1), P = 0.05). LXR activation increased white adipose
      tissue mRNA levels of Glut4, Acc1 and Fasin ob/ob mice only. In conclusion, LXR
      induced blood glucose lowering in ob/ob mice was attributable to increased
      peripheral glucose uptake and metabolism, physiologically reflected in a slightly
      improved insulin sensitivity. Remarkably, steatosis associated with LXR
      activation did not affect hepatic insulin sensitivity.

PMID- 15941784
TI  - Impaired glucagon secretory responses in mice lacking the type 1 sulfonylurea
      receptor.
AB  - Pancreatic alpha-cells, like beta-cells, express ATP-sensitive K(+) (K(ATP))
      channels. To determine the physiological role of K(ATP) channels in alpha-cells,
      we examined glucagon secretion in mice lacking the type 1 sulfonylurea receptor
      (Sur1). Plasma glucagon levels, which were increased in wild-type mice after an
      overnight fast, did not change in Sur1 null mice. Pancreas perfusion studies
      showed that Sur1 null pancreata lacked glucagon secretory responses to
      hypoglycemia and to synergistic stimulation by arginine. Pancreatic alpha-cells
      isolated from wild-type animals exhibited oscillations of intracellular free
      Ca(2+) concentration ([Ca(2+)](i)) in the absence of glucose that became
      quiescent when the glucose concentration was increased. In contrast, Sur1 null
      alpha-cells showed continuous oscillations in [Ca(2+)](i) regardless of the
      glucose concentration. These findings indicate that K(ATP) channels in alpha
      cells play a key role in regulating glucagon secretion, thereby adding to the
      paradox of how mice that lack K(ATP) channels maintain euglycemia.

PMID- 15941785
TI  - A proinflammatory tumor that activates protein degradation sensitizes rats to
      catabolic effects of endotoxin.
AB  - Chronic or acute inflammation may participate in the etiology of cancer cachexia.
      To investigate the interaction between tumor and a secondary inflammatory
      stimulus on muscle wasting, rats with and without tumors (Yoshida ascites
      hepatoma) received low doses of endotoxin (LPS, 400 microg/kg sc) or saline.
      Nitrogen balance was measured 24 h before and after LPS/saline. Epitrochlearis
      muscle was used to measure in vitro protein metabolism, and gastrocnemius muscle
      was used for quantification of the mRNA for components of the ubiquitin
      proteolytic pathway. The YAH reduced muscle mass (P = 0.002), increased muscle
      protein degradation (P = 0.042), and elevated mRNA expression of components of
      the ubiquitin proteolytic pathway (P < 0.01) including ubiquitin, ubiquitin
      conjugating enzyme E2(14k), and ubiquitin ligases muscle RING Finger 1 and
      atrogin-1. Although the selected low dose of LPS had no impact on protein
      metabolism in control rats, LPS in rats bearing YAH caused weight loss (P =
      0.0007), lowered nitrogen balance (P = <0.0001), and increased muscle protein
      degradation (P = 0.0336). In conclusion, the presence of a tumor can potentiate
      whole body and muscle-specific catabolic losses of protein in response to a
      stimulus that is not catabolic in healthy animals. This effect might be dependent
      on the inflammatory nature of the tumor.

PMID- 15941786
TI  - Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome
      proliferator-activated receptor-alpha.
AB  - Chronic activation of adipocyte beta-adrenergic receptors induces remodeling of
      white adipose tissue (WAT) that includes a transient inflammatory response
      followed by mitochondrial biogenesis, induction of fatty acid oxidation genes,
      and elevation of tissue oxidative metabolism. Gene profiling experiments of WAT
      during remodeling induced by the beta(3)-adrenergic receptor agonist CL-316,243
      (CL) suggested that peroxisome proliferator-activated receptor-alpha (Ppara),
      which is upregulated by CL, might be an important transcriptional regulator of
      that process. Histological, physiological, and molecular analysis of CL-induced
      remodeling in wild-type mice and mice lacking Ppara demonstrated that Ppara was
      important for inducing adipocyte mitochondrial biogenesis and upregulating genes
      involved in fatty acid oxidation. Furthermore, Ppara-deficient mice exhibited
      sustained WAT inflammation during CL treatment, indicating that upregulation of
      Ppara limits proinflammatory signaling during chronic lipolytic activation.
      Together, these data support the hypothesis that WAT remodeling is an adaptive
      response to excessive fatty acid mobilization whereby Ppara and its downstream
      targets elevate fatty acid catabolism and suppress proinflammatory signaling.

PMID- 15941787
TI  - Metabolic and cellular plasticity in white adipose tissue I: effects of beta3
      adrenergic receptor activation.
AB  - Selective agonists of beta(3)-adrenergic receptors (Adrb3) exhibit potent anti
      diabetes properties in rodent models when given chronically, yet the mechanisms
      involved are poorly understood. A salient feature of chronic Adrb3 activation is
      pronounced remodeling of white adipose tissue (WAT), which includes mitochondrial
      biogenesis and elevation of metabolic rate. To gain insights into potential
      mechanisms underlying WAT remodeling, the time course of remodeling induced by
      the Adrb3 agonist CL-316,243 (CL) was analyzed using histological, physiological,
      and global gene profiling approaches. The results indicate that continuous CL
      treatment induced a transient proinflammatory response that was followed by
      cellular proliferation among stromal cells and multilocular adipocytes. CL
      treatment strongly fragmented the central lipid storage droplet of mature
      adipocytes and induced mitochondrial biogenesis within these cells. Mitochondrial
      biogenesis was correlated with the upregulation of genes involved in fatty acid
      oxidation and mitochondrial electron transport activity. The elevated catabolic
      activity of WAT was temporally correlated with upregulation of peroxisome
      proliferator-activated receptor-alpha and its target genes, suggesting
      involvement of this transcription factor in coordinating the gene program that
      elevates WAT catabolic activity.

PMID- 15941788
TI  - The cover. T.B. Harlem.

PMID- 15941789
TI  - Basic science guides design of new TB vaccine candidates.

PMID- 15941790
TI  - TB drug research picks up the pace.

PMID- 15941791
TI  - Group targets surging TB in Africa.

PMID- 15941792
TI  - A TB scientist reflects on the continuing struggle against a global threat.
      Interview by Mike Mitka.

PMID- 15941796
TI  - Guidelines for cardiopulmonary resuscitation.

PMID- 15941797
TI  - Continuous positive airway pressure and postoperative hypoxemia.

PMID- 15941798
TI  - Cocaine-induced acute hepatitis and thrombotic microangiopathy.

PMID- 15941799
TI  - Tuberculosis in incarcerated youth in Texas.

PMID- 15941800
TI  - Effect of routine isoniazid preventive therapy on tuberculosis incidence among
      HIV-infected men in South Africa: a novel randomized incremental recruitment
      study.
AB  - CONTEXT: Tuberculosis preventive therapy reduces tuberculosis incidence among
      human immunodeficiency virus (HIV)-infected individuals in clinical trials, but
      implementation has been limited and there are no data on effectiveness under
      routine conditions. OBJECTIVE: To determine the effect on tuberculosis incidence
      of a clinic providing isoniazid preventive therapy to HIV-infected adults under
      routine conditions. DESIGN, SETTING, AND PARTICIPANTS: Randomized intervention
      study with a novel incremental recruitment design. Between 1999 and 2001 (before
      antiretroviral therapy was available), 1655 HIV-infected male employees of a
      South African gold-mining company (median age, 37 years) were enrolled in the
      study. Median follow-up was 22.1 months. INTERVENTION: Employees were invited in
      random sequence to attend a workplace HIV clinic. Isoniazid, 300 mg/d, was self
      administered for 6 months among attendees with no evidence of active
      tuberculosis. MAIN OUTCOME MEASURE: Incidence of tuberculosis (including both
      first and recurrent episodes) during the periods before and after clinic
      enrollment. RESULTS: A total of 1016 of 1655 men included in the analysis
      attended the clinic at least once. Six hundred seventy-nine (97%) of 702 men
      eligible to start primary isoniazid preventive therapy did so. The tuberculosis
      incidence rate before vs after clinic enrollment was 11.9 vs 9.0 per 100 person
      years, respectively (incidence rate ratio [IRR] after adjustment for calendar
      period, 0.68; 95% confidence interval [CI], 0.48-0.96). In a multivariable
      analysis adjusting for calendar period, age, and silicosis grade, the
      tuberculosis IRR for clinic enrollment was 0.62 (95% CI, 0.43-0.89). In a further
      analysis excluding individuals with a history of tuberculosis (and, hence,
      ineligible for isoniazid preventive therapy), the adjusted IRR for clinic
      enrollment was 0.54 (95% CI, 0.35-0.83). CONCLUSIONS: Enrollment in a clinic
      offering primary isoniazid preventive therapy to HIV-infected adults reduced
      tuberculosis incidence by 38% overall and by 46% among individuals with no
      history of tuberculosis prior to the study. Tuberculosis incidence remained high
      despite isoniazid preventive therapy, and further work is needed to determine how
      to use additional interventions most effectively to reduce morbidity and
      mortality due to tuberculosis in HIV-infected persons.

PMID- 15941801
TI  - Drug-resistant tuberculosis, clinical virulence, and the dominance of the Beijing
      strain family in Russia.
AB  - CONTEXT: Tuberculosis and multidrug-resistant tuberculosis is a serious public
      health problem in Russia. OBJECTIVE: To address the extent of "Beijing strain"
      transmission in the prison/civil sectors and the association of drug resistance,
      clinical, and social factors with the Beijing genotype. DESIGN AND SETTING: Cross
      sectional population-based molecular epidemiological study of all civilian and
      penitentiary tuberculosis facilities in the Samara region, Russia. PATIENTS:
      Consecutively recruited patients with bacteriologically proven tuberculosis (n =
      880). MAIN OUTCOME MEASURE: Proportion of Beijing strains and association with
      drug resistance, human immunodeficiency virus infection, imprisonment,
      radiological, clinical, and other social factors. RESULTS: Beijing-family strains
      (identified by spoligotyping and composed of 2 main types by mycobacterial
      interspersed repetitive unit analysis) were predominant: 586/880 (66.6%; 95%
      confidence interval [CI], 63.4%-69.7%) with a significantly higher prevalence in
      the prison population (rate ratio [RR], 1.3; 95% CI, 1.2-1.5) and those aged
      younger than 35 years (RR, 1.2; 95% CI, 1.0-1.3). Comparable proportions were co
      infected with the human immunodeficiency virus ( approximately 10%), concurrent
      hepatitis B and C (21.6%), drank alcohol ( approximately 90%), smoked (
      approximately 90%), and had a similar sexual history. Drug resistance was nearly
      2-fold higher in patients infected with Beijing strains compared with non-Beijing
      strains: multidrug resistance (RR, 2.4; 95% CI, 1.9-3.0), for isoniazid (RR, 1.8;
      95% CI, 1.5-2.1), for rifampicin (RR, 2.2; 95% CI, 1.7-2.7), for streptomycin
      (RR, 1.9; 95% CI, 1.5-2.3), and for ethambutol (RR, 2.2; 95% CI, 1.6-3.2).
      Univariate analysis demonstrated that male sex (odds ratio [OR], 1.5; 95% CI, 1.1
      1.9), advanced radiological abnormalities (OR, 3.3; 95% CI, 1.3-8.4),
      homelessness (OR, 5.6; 95% CI, 1.1-6.3), and previous imprisonment (OR, 2.0; 95%
      CI, 1.5-2.7) were strongly associated with Beijing-strain family disease.
      Multivariate analysis supported previous imprisonment to be a risk factor (OR,
      2.0; 95% CI, 1.4-3.3) and night sweats to be less associated (OR 0.7; 95% CI, 0.5
      1.0) with Beijing-strain disease. CONCLUSIONS: Drug resistance and previous
      imprisonment but not human immunodeficiency virus co-infection were significantly
      associated with Beijing-strain infection. There was evidence that Beijing
      isolates caused radiologically more advanced disease.

PMID- 15941802
TI  - Multidrug resistance among persons with tuberculosis in California, 1994-2003.
AB  - CONTEXT: Between 1994 and 2003, tuberculosis (TB) cases in California declined
      33% (4834 to 3224). However, in 2003 California reported the largest number of
      cases in the nation, and over the past decade the proportion of cases with
      multidrug-resistant tuberculosis (MDR-TB) has not decreased. OBJECTIVE: To
      describe the magnitude, trends, geographic distribution, clinical
      characteristics, risk factors, and outcomes of MDR-TB cases reported to the
      California registry of Reports of Verified Cases of TB. DESIGN, SETTING, AND
      CASES: Analysis of 38,291 TB cases reported from all 61 local health
      jurisdictions in California during 1994-2003. Multidrug-resistant TB was defined
      as resistance to at least isoniazid and rifampin. MAIN OUTCOME MEASURES: Results
      of univariate and multivariable analyses of MDR-TB magnitude, trends, geographic
      distribution, clinical characteristics, associated factors, and outcomes.
      RESULTS: Of 38,291 reported TB cases, 28,712 (75%) were tested for resistance to
      at least isoniazid and rifampin; of these, 407 MDR-TB cases (1.4%) were reported
      from 38 of 61 California health jurisdictions (62%); the proportion of MDR-TB
      cases did not significantly change over the study period (P = .87). Cases of MDR
      TB were twice as likely to have cavitary lesions compared with non-MDR-TB cases
      (P<.001) and were 7 times more likely to have reported previous treatment for TB
      (P<.001). Of MDR-TB cases with outcomes, 231 (67%) completed therapy, and those
      with MDR-TB were significantly less likely to complete therapy than those without
      MDR-TB (P<.001). Multivariate analysis identified previous TB diagnosis, positive
      acid-fast bacilli sputum smear results, Asian/Pacific Islander ethnicity, time in
      the United States less than 5 years at the time of diagnosis, and outcomes of
      "died" and "moved" as factors associated with MDR-TB. CONCLUSIONS: Multidrug
      resistant TB, an airborne disease with limited, costly treatment options,
      persists in 1% to 2% of all cases despite California's control efforts. Local and
      global TB control efforts are needed to prevent the further development and
      spread of MDR-TB.

PMID- 15941803
TI  - Clinical and radiographic correlates of primary and reactivation tuberculosis: a
      molecular epidemiology study.
AB  - CONTEXT: The traditional teaching that pulmonary tuberculosis characterized by
      lymphadenopathy, effusions, and lower or mid lung zone infiltrates on chest
      radiography represents "primary" disease from recently acquired infection,
      whereas upper lobe infiltrates and cavities represent secondary or reactivation
      disease acquired in the more distant past, is not based on well-established
      clinical evidence. Furthermore, it is not known whether the atypical radiograph
      common in human immunodeficiency virus (HIV)-associated tuberculosis is due to a
      preponderance of primary progressive disease or altered immunity. OBJECTIVE: To
      analyze the relationship between recently acquired and remotely acquired
      pulmonary tuberculosis, clinical and demographic variables, and radiographic
      features by using molecular fingerprinting and conventional epidemiology. DESIGN,
      SETTING, AND POPULATION: A retrospective, hospital-based series of 456 patients
      treated at a New York City medical center between 1990 and 1999. Eligible
      patients had to have had at least 1 positive respiratory culture for
      Mycobacterium tuberculosis and available radiographic data. MAIN OUTCOME
      MEASURES: Radiographic appearance as measured by the presence or absence of 6
      features: upper lobe infiltrate, cavitary lesion, adenopathy, effusions, lower or
      mid lung zone infiltrate, and miliary pattern. Radiographs were considered
      typical if they had an upper lobe infiltrate or cavity whether or not other
      features were present. Atypical radiographs were those that had adenopathy,
      effusion, or mid lower lung zone infiltrates or had none of the above features.
      RESULTS: Human immunodeficiency virus infection was most commonly associated with
      an atypical radiographic appearance on chest radiograph with an odds ratio of
      0.20 (95% confidence interval, 0.13-0.31). Although a clustered fingerprint,
      representing recently acquired disease, was associated with typical radiograph in
      univariate analysis (odds ratio, 0.68; 95% confidence interval, 0.47-0.99), the
      association was lost when adjusted for HIV status. CONCLUSIONS: Time from
      acquisition of infection to development of clinical disease does not reliably
      predict the radiographic appearance of tuberculosis. Human immunodeficiency virus
      status, a probable surrogate for the integrity of the host immune response, is
      the only independent predictor of radiographic appearance. The altered
      radiographic appearance of pulmonary tuberculosis in HIV is due to altered
      immunity rather than recent acquisition of infection and progression to active
      disease.

PMID- 15941804
TI  - Mycobacterium tuberculosis infection in health care workers in rural India:
      comparison of a whole-blood interferon gamma assay with tuberculin skin testing.
AB  - CONTEXT: Mycobacterium tuberculosis infection in health care workers has not been
      adequately studied in developing countries using newer diagnostic tests.
      OBJECTIVES: To estimate latent tuberculosis infection prevalence in health care
      workers using the tuberculin skin test (TST) and a whole-blood interferon gamma
      (IFN-gamma) assay; to determine agreement between the tests; and to compare their
      correlation with risk factors. DESIGN, SETTING, AND PARTICIPANTS: A cross
      sectional comparison study of 726 health care workers aged 18 to 61 years (median
      age, 22 years) with no history of active tuberculosis conducted from January to
      May 2004, at a rural medical school in India. A total of 493 (68%) of the health
      care workers had direct contact with patients with tuberculosis and 514 (71%) had
      BCG vaccine scars. INTERVENTIONS: Tuberculin skin testing was performed using 1
      TU dose of purified protein derivative RT23, and the IFN-gamma assay was
      performed by measuring IFN-gamma response to early secreted antigenic target 6,
      culture filtrate protein 10, and a portion of tuberculosis antigen TB7.7. MAIN
      OUTCOME MEASURES: Agreement between TST and the IFN-gamma assay, and comparison
      of the tests with respect to their association with risk factors. RESULTS: A
      large proportion of the health care workers were latently infected; 360 (50%)
      were positive by either TST or IFN-gamma assay, and 226 (31%) were positive by
      both tests. The prevalence estimates of TST and IFN-gamma assay positivity were
      comparable (41%; 95% confidence interval [CI], 38%-45% and 40%; 95% CI, 37%-43%,
      respectively). Agreement between the tests was high (81.4%; kappa = 0.61; 95% CI,
      0.56-0.67). Increasing age and years in the health profession were significant
      risk factors for both IFN-gamma assay and TST positivity. BCG vaccination had
      little impact on TST and IFN-gamma assay results. CONCLUSIONS: Our study showed
      high latent tuberculosis infection prevalence in Indian health care workers, high
      agreement between TST and IFN-gamma assay, and similar association between
      positive test results and risk factors. Although TST and IFN-gamma assay appear
      comparable in this population, they have different performance and operational
      characteristics; therefore, the decision to select one test over the other will
      depend on the population, purpose of testing, and resource availability.

PMID- 15941805
TI  - Discrepancy between the tuberculin skin test and the whole-blood interferon gamma
      assay for the diagnosis of latent tuberculosis infection in an intermediate
      tuberculosis-burden country.
AB  - CONTEXT: A recently developed whole-blood interferon gamma (IFN-gamma) assay
      based on stimulation with the Mycobacterium tuberculosis-specific antigens early
      secreted antigenic target 6 and culture filtrate protein 10 shows promise for the
      diagnosis of latent tuberculosis (TB) infection. OBJECTIVE: To compare the
      tuberculin skin test (TST) and the whole-blood IFN-gamma assay in the diagnosis
      of latent TB infection according to the intensity of exposure. DESIGN AND
      SETTING: A prospective comparison between the whole-blood IFN-gamma assay and the
      TST using a 2-TU dose of purified protein derivative RT23 in a population with
      intermediate TB burden was conducted sequentially between February 1, 2004, and
      February 28, 2005, in a Korean tertiary referral hospital. PARTICIPANTS: Of 273
      participants, 220 (95.7%) had received BCG vaccine. Participants were grouped
      according to their risk of infection: group 1, no identifiable risk of M
      tuberculosis infection (n = 99); group 2, recent casual contacts (n = 72); group
      3, recent close contacts (n = 48); group 4, bacteriologically or pathologically
      confirmed TB patients (n = 54). MAIN OUTCOME MEASURES: Levels of agreement
      between the TST and the IFN-gamma assay and the likelihood of infection in the
      various groups. RESULTS: For the TST with a 10-mm induration cutoff, the positive
      response rate in group 1 was 51%; group 2, 60%; group 3, 71%, and group 4, 78%.
      For the IFN-gamma assay, the positive response rate in group 1 was 4%; group 2,
      10%; group 3, 44%; and group 4, 81%. The overall agreement between the TST and
      the IFN-gamma assay in healthy volunteers was kappa = 0.16. The odds of a
      positive test result per unit increase in exposure across the 4 groups increased
      by a factor of 5.31 (95% confidence interval [CI], 3.62-7.79) for the IFN-gamma
      assay and by a factor of 1.52 (95% CI, 1.20-1.91) for the TST (P<.001). Using a
      15-mm induration cutoff for the TST did not make a substantial difference to the
      test results. CONCLUSION: The IFN-gamma assay is a better indicator of the risk
      of M tuberculosis infection than TST in a BCG-vaccinated population.

PMID- 15941806
TI  - Tuberculosis and homelessness in the United States, 1994-2003.
AB  - CONTEXT: Tuberculosis (TB) rates among US homeless persons cannot be calculated
      because they are not included in the US Census. However, homelessness is often
      associated with TB. OBJECTIVES: To describe homeless persons with TB and to
      compare risk factors and disease characteristics between homeless and nonhomeless
      persons with TB. DESIGN AND SETTING: Cross-sectional analysis of all verified TB
      cases reported into the National TB Surveillance System from the 50 states and
      the District of Columbia from 1994 through 2003. MAIN OUTCOME MEASURES: Number
      and proportion of TB cases associated with homelessness, demographic
      characteristics, risk factors, disease characteristics, treatment, and outcomes.
      RESULTS: Of 185,870 cases of TB disease reported between 1994 and 2003, 11,369
      were among persons classified as homeless during the 12 months before diagnosis.
      The annual proportion of cases associated with homelessness was stable (6.1%
      6.7%). Regional differences occurred with a higher proportion of TB cases
      associated with homelessness in western and some southern states. Most homeless
      persons with TB were male (87%) and aged 30 to 59 years. Black individuals
      represented the highest proportion of TB cases among the homeless and
      nonhomeless. The proportion of homeless persons with TB who were born outside the
      United States (18%) was lower than that for nonhomeless persons with TB (44%). At
      the time of TB diagnosis, 9% of homeless persons were incarcerated, usually in a
      local jail; 3% of nonhomeless persons with TB were incarcerated. Compared with
      nonhomeless persons, homeless persons with TB had a higher prevalence of
      substance use (54% alcohol abuse, 29.5% noninjected drug use, and 14% injected
      drug use), and 34% of those tested had coinfection with human immunodeficiency
      virus. Compared with nonhomeless persons, TB disease in homeless persons was more
      likely to be infectious but not more likely to be drug resistant. Health
      departments managed 81% of TB cases in homeless persons. Directly observed
      therapy, used for 86% of homeless patients, was associated with timely completion
      of therapy. A similar proportion in both groups (9%) died from any cause during
      therapy. CONCLUSIONS: Individual TB risk factors often overlap with risk factors
      for homelessness, and the social contexts in which TB occurs are often complex
      and important to consider in planning TB treatment. Nevertheless, given good case
      management, homeless persons with TB can achieve excellent treatment outcomes.

PMID- 15941807
TI  - Evolution of tuberculosis control and prospects for reducing tuberculosis
      incidence, prevalence, and deaths globally.
AB  - CONTEXT: The United Nations Millennium Development Goals (MDGs) are stimulating
      more rigorous evaluations of the impact of DOTS (the WHO-recommended approach to
      tuberculosis control based on 5 essential elements) and other possible strategies
      for tuberculosis (TB) control. OBJECTIVE: To evaluate the prospects for detecting
      70% of new sputum smear-positive cases and successfully treating 85% of these by
      the end of 2005, for reducing TB incidence, and for halving TB prevalence and
      deaths globally between 1990 and 2015, as specified by the MDGs. DATA SOURCES: TB
      case notifications (1980-2003) from DOTS and non-DOTS programs and cohort
      treatment outcomes (1994-2002) reported annually to the World Health Organization
      (WHO) by up to 200 countries, TB death registrations, and prevalence surveys of
      infection and disease. STUDY SELECTION: Case notification series that reflect
      trends in incidence, treatment outcomes from DOTS cohorts, death statistics from
      countries with WHO-validated vital registration systems, and national prevalence
      surveys of infection and disease. DATA EXTRACTION: Case reports, treatment
      outcomes, prevalence surveys, and death registrations from WHO's global TB
      database covering 1990-2003 to estimate TB incidence, prevalence, and death rates
      through 2015 for 9 epidemiologically different world regions. DATA SYNTHESIS: TB
      incidence increased globally in 2003, but incidence, prevalence, and death rates
      were approximately stable or decreased in 7 of 9 regions. The exceptions were
      regions of Africa with low (<4% in adults 15-49 years) and high rates (> or =4%)
      of HIV infection. The global detection rate of new smear-positive cases by DOTS
      programs increased from 11% in 1995 to 45% in 2003 (with the lowest case
      detection rates in Eastern Europe and the highest rates in the Western Pacific)
      and could reach 60% by 2005. More than 17 million patients were treated in DOTS
      programs between 1994 and 2003, with overall treatment success rates more than
      80% since 1998. In 2003, overall reported treatment success was 82%, with much
      variation among regions. The highest rates were reported in the Western Pacific
      region (89%) and lowest rates in African countries with high and low HIV
      infection rates (71% and 74%, respectively), in established market economies
      (77%), and in Eastern Europe (75%). To halve the prevalence rate by 2015, TB
      control programs must reach global targets for detection (70%) and treatment
      success (85%) and also reduce the incidence rate by at least 2% annually. To
      halve the death rate, incidence must decrease more steeply, by at least 5% to 6%
      annually. CONCLUSION: Reduction of TB incidence, prevalence, and deaths by 2015
      could be achieved in most of the world, but the challenge will be greatest in
      Africa and Eastern Europe.

PMID- 15941808
TI  - Update on the treatment of tuberculosis and latent tuberculosis infection.
AB  - Tuberculosis (TB) has emerged as a global public health epidemic. Despite
      decreasing numbers of cases in the United States since 1992, TB remains a serious
      public health problem among certain patient populations and is highly prevalent
      in many urban areas. The responsibility for prescribing an appropriate drug
      regimen and ensuring that treatment is completed is assigned to the public health
      program or the clinician not to the patient. The initial prescribed regimen for
      the treatment of TB usually consists of 4 drugs: isoniazid, rifampin,
      pyrazinamide, and ethambutol. The minimum length for the treatment of drug
      susceptible TB with a rifampin-based regimen is 6 to 9 months. Providing
      medications directly to the patient and watching him/her swallow the anti-TB
      drugs, which is termed directly observed therapy, is recommended for all patients
      diagnosed with TB and can help ensure higher completion rates, prevent the
      emergence of drug resistant TB, and enhance TB control. There has been renewed
      interest in the treatment of those with latent TB infection as a TB-control
      strategy in the United States for eliminating the large reservoir of individuals
      at risk for progression to TB. The 2 broad categories of persons who should be
      tested for latent TB infection are those who are likely to have been recently
      infected (such as contacts to infectious TB cases) and persons who are at
      increased risk of progression to TB disease following infection with
      Mycobacterium tuberculosis (eg, human immunodeficiency virus infection and
      selected medical conditions; recent immigrants to the United States from high TB
      burden countries). The preferred regimen for the treatment of latent TB infection
      is 9 months of isoniazid. There is now renewed interest in and great need for the
      development of new drugs to treat TB and latent TB infection.

PMID- 15941809
TI  - Diagnosis of latent tuberculosis infection: measure for measure.

PMID- 15941810
TI  - Multidrug-resistant tuberculosis: news from the front.

PMID- 15941811
TI  - Tuberculosis, vulnerability, and access to quality care.

PMID- 15941813
TI  - JAMA patient page. Tuberculosis.

PMID- 15941812
TI  - Tuberculosis--a global problem requiring a global solution.

PMID- 15941814
TI  - Inhalation dose due to presence of 131I in air above septic tank system of an
      endocrinology hospital.
AB  - We present here measurements of the 131I concentration for both: gaseous and
      aerosol fraction of 131I in the air above the septic tank containing wastes from
      medical application of this isotope. Aerosols were collected using air filters,
      whereas gaseous forms of iodine were trapped in KI impregnated charcoal double
      layer cartridge. Besides an active method (pumping of the air through system of
      filters) an attempt for using a passive method (charcoal traps) for monitoring of
      radio-iodine is described. For better characterisation of a site the external
      kerma was determined by means of G-M and TLD techniques as well as the activity
      kept in the septic tank was measured by gamma spectrometry. Results show that the
      activity of the aerosol fraction can be neglected compared to that of the gaseous
      fraction. He measured activity of air is low, on the level of 1 Bq m(-3), even
      during simulated failure of the ventilation system. Estimated inhalation dose for
      the serviceman of septic tanks is low ( approximately 10%) compared with external
      dose obtained by such person due to gamma radiation from the tank (on the level
      approximately 500 nSv h(-1)). Therefore, the concept of passive monitoring of the
      iodine in air was abandoned. Also estimated is the efficiency of 131I reduction
      by a charcoal filter of the ventilation system and 131I input to the environment
      by the ventilation chimney.

PMID- 15941815
TI  - Patient and personnel dosimetry in endovascular radiotherapy with 90Sr/90Y
      sources.
AB  - Endovascular brachytherapy (EVBT) is an established treatment to reduce the
      probability of restenosis after a percutaneous coronary intervention. The purpose
      of this study was to assess (1) the manufacturer's stated dosimetric data for
      (90)Sr/(90)Y source trains to be used in EVBT and (2) the procedure-related
      radiation burden. The radiation fields in water around six (90)Sr/(90)Y source
      trains were studied using phantoms made of 'solid water' and MD55-2 radiochromic
      films. The water equivalence of the phantom material was tested by applying
      quantitative computed tomography. Thermoluminescence dosemeters were used to
      assess personal radiation burden and crosscheck the dose distribution along the
      source trains. Technical failure was observed in one source train and this train
      was excluded from analysis. The measured dose rate in water at 2 mm radial
      distance was on average 8% higher than the manufacture's stated value (range of
      measured to stated values 1.05--1.15). The dose rate decreased exponentially with
      radial distance between 2 and 6 mm. The dose rate in contact with the source
      viewing window of the delivery devices ranged between 0.5 and 7.5 mGy h(-1). Low
      energy photons were the main contributors to personal dose.

PMID- 15941816
TI  - From practice research to public policy--the Ministerial Summit on Health
      Research.
AB  - OBJECTIVE: To report on the outcomes of discussions on the role of research in
      the improvement of population health that took place at the Ministerial Summit on
      Health Research. DATA SOURCES: Information was gathered from presentations and
      discussions at the Ministerial Summit on Health Research conducted in Mexico City
      November 16-20, 2004. DATA SYNTHESIS: Strategies to strengthen health systems
      through closer collaboration between researchers and policy makers were debated.
      Consideration was given to persisting inequalities in health research, including
      the 10/90 gap (10% of health research expenditure is devoted to diseases
      responsible for 90% of the world's disease burden), the "know-do" gap (the gap
      between research knowledge and professional practice), and the divide in access
      to health information. Adopting measures to address human resource shortages was
      seen as critical. Participants at the Summit issued "The Mexico Statement on
      Health Research." CONCLUSIONS: All stakeholders must develop the political will
      to share information, resources, and experiences to ensure that practice research
      and public policy develop in accordance with patients' needs.

PMID- 15941817
TI  - Quality assurance instrument focusing on patient counseling.
AB  - BACKGROUND: Patient counseling is a professional service provided by community
      pharmacists. To assess the quality of these services, specific quality assurance
      instruments are needed. OBJECTIVE: To develop a validated, easy-to-use patient
      counseling quality assurance instrument for community pharmacists. The
      development process was part of a national project to enhance patient counseling
      in community pharmacies (TIPPA 2000-2003). METHODS: A modified Delphi method was
      used with 2 expert panels: Panel 1, consisting of experienced pharmacy
      practitioners (n = 10), and Panel 2, consisting of academic and professional
      experts (n = 10). The final consensus was assessed by a Delphi questionnaire
      round involving both panels, the employers of Panel 1 members (n = 5), and the
      members of the executive board of the TIPPA project (n = 10), comprising 35
      people (response rate 74%; n = 26). RESULTS: The first Delphi round yielded a
      high consensus, with the level of agreement varying between 69% and 100%. All but
      one item met the predefined criteria for approval. A total of 16 indicators were
      identified in 3 quality dimensions: patient (4 indicators), process (6), and
      learning and innovations (6). Strategy and vision of the pharmacy in patient
      counseling formed the core of the instrument. CONCLUSIONS: The modified Delphi
      method proved to be applicable in the development process of an instrument
      assessing patient counseling services. The instrument comprehensively takes into
      account factors related to quality assurance of counseling practices.

PMID- 15941818
TI  - Phosphodiesterase 5 inhibitors for erectile dysfunction.
AB  - OBJECTIVE: To review the pharmacologic and clinical trial data of the Food and
      Drug Administration-approved phosphodiesterase 5 (PDE5) inhibitors for the
      treatment of erectile dysfunction (ED). DATA SOURCES: Primary research and review
      articles were identified through a search of ScienceDirect, PubMed/MEDLINE, and
      International Pharmaceutical Abstracts (1990-August 2004). The following search
      terms were used in the Medicine Dentistry and Pharmacology, Toxicology, and
      Pharmaceutical Sciences subcategories: phosphodiesterase 5 inhibitor, PDE5
      inhibitor, erectile dysfunction, sildenafil, vardenafil, tadalafil,
      prostatectomy, and diabetes. Web of Science (1990-August 2004) was used to search
      for additional abstracts using the same search terms as above. The package
      inserts for sildenafil, vardenafil, and tadalafil were also consulted. STUDY
      SELECTION AND DATA EXTRACTION: All identified research, review articles, and
      abstracts were assessed for relevance, and all relevant information was included.
      Priority was given to the primary medical literature and clinical trial reports.
      DATA SYNTHESIS: ED is a common disorder in males with increased prevalence
      associated with age and presence of cardiovascular disease, prostatectomy, or
      diabetes mellitus. Sildenafil, vardenafil, and tadalafil are selective PDE5
      inhibitors currently available for treatment of ED. Their pharmacology and
      pharmacokinetics vary slightly, but with potentially important clinical
      differences in duration of activity; all have similar clinical efficacy and
      adverse effect profiles in patients with ED of various causes. CONCLUSIONS:
      Sildenafil, vardenafil, and tadalafil are safe and effective PDE5 inhibitors for
      the treatment of ED.

PMID- 15941820
TI  - Comment: When does pharmaceutical care impact health outcomes? A comparison of
      community pharmacy-based studies of pharmaceutical care for patients with asthma.

PMID- 15941821
TI  - Selective serotonin-reuptake inhibitors in the treatment of premature
      ejaculation.
AB  - OBJECTIVE: To review the use of selective serotonin-reuptake inhibitors (SSRIs)
      in the treatment of premature ejaculation. DATA SOURCES: Articles were retrieved
      through a MEDLINE search (1966-January 2004). Search terms used to identify
      articles included serotonin uptake inhibitors, premature ejaculation, rapid
      ejaculation, and sexual behavior, as well as the generic names of currently
      available SSRIs: fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and
      escitalopram. The literature search was limited to articles published in the
      English language containing human subjects. STUDY SELECTION AND DATA EXTRACTION:
      Articles obtained through the literature search were evaluated, and randomized
      controlled trials were included in this review. Information from noncontrolled
      trials or case reports was considered for inclusion if it contributed to the
      completeness of this review and if it was the highest level of evidence
      available. DATA SYNTHESIS: Premature ejaculation is a commonly reported sexual
      difficulty. Delayed ejaculation is a widely reported sexual adverse effect of
      SSRIs. In some men exhibiting premature ejaculation, the ability of the SSRIs to
      delay ejaculation has been therapeutic. Trials evaluating the ejaculation
      delaying ability of SSRIs demonstrated that paroxetine, fluoxetine, sertraline,
      and citalopram produce a statistically significant increase in the ejaculation
      latency time compared with placebo. CONCLUSIONS: Taking advantage of the
      ejaculation-delaying effects of SSRIs increases the treatment options available
      to prescribers and patients. Convenience and minimal adverse effect profile make
      these agents an alternative to previously used behavior modalities and older
      pharmacologic agents. Although some questions still surround the details of their
      use, SSRIs have the potential to improve the quality of life for men with
      premature ejaculation and their partners.

PMID- 15941822
TI  - Severe hyperglycemia during renally adjusted gatifloxacin therapy.
AB  - OBJECTIVE: To report a case of severe hyperglycemia in a nondiabetic patient
      receiving gatifloxacin that was properly dosed based on renal function. CASE
      SUMMARY: A 65-year-old nondiabetic female with progressive renal dysfunction was
      admitted for severe hyperglycemia. The patient had received 9 days of a 10-day
      course of renally adjusted therapy with gatifloxacin 200 mg/day for bronchitis.
      Her blood glucose level on admission was 1121 mg/dL, at which point the
      gatifloxacin was discontinued. After several days of intensive insulin therapy,
      the blood glucose levels returned to normal, and the patient was subsequently
      discharged. DISCUSSION: Gatifloxacin-induced hyperglycemia has been reported in
      the literature, but based on a MEDLINE search (1966-December 2004), no such cases
      were found in a nondiabetic patient receiving the proper gatifloxacin dose,
      adjusted for degree of renal insufficiency. The available case reports seem to
      suggest the increase in blood glucose concentrations could have been precipitated
      by high drug concentrations in patients not receiving the renally adjusted dose
      or in those with preexisting, undiagnosed diabetes. A definite mechanism of
      action for gatifloxacin-induced hyperglycemia is not known. The Naranjo
      probability scale revealed a probable adverse reaction of hyperglycemia
      associated with gatifloxacin therapy. CONCLUSIONS: Healthcare professionals
      should be more aware of the possible development of hyperglycemia in all patients
      taking gatifloxacin, including those who are not diabetic and those receiving
      appropriately reduced doses for renal dysfunction.

PMID- 15941823
TI  - Venous thromboembolism prevention in acutely ill nonsurgical patients.
AB  - OBJECTIVE: To review recent advances in the prevention of venous thromboembolism
      (VTE) in acutely ill nonsurgical inpatients. DATA SOURCES: A MEDLINE search (1966
      March 2005) was done to identify relevant articles relating to prevention of VTE
      in acutely ill nonsurgical inpatients. STUDY SELECTION AND DATA EXTRACTION: Four
      major prophylaxis trials, one registry, one guideline, and supporting articles
      representative of the subject matter from the last few years were included. DATA
      SYNTHESIS: Enoxaparin, dalteparin, fondaparinux, and unfractionated heparin 5000
      units every 8 hours are effective in reducing the risk of VTE in acutely ill
      medical patients, but such prophylaxis is currently underused. Barriers to be
      overcome include recognition of the importance of VTE in this population,
      definition of the optimal strategy to assess risks, optimal timing of the risk
      assessment, optimal prophylactic regimen for a given level of risk or disease
      state, and optimal duration of prophylaxis. We recommend that acutely ill medical
      inpatients should be risk-stratified early in their hospitalization. At this
      time, the specific risk-assessment protocol should be derived from the trial(s)
      of the available formulary agent(s). Decisions about providing prophylaxis must
      also be made considering anticoagulant contraindications and renal function.
      Mechanical methods of prophylaxis should be considered as monotherapy only if an
      anticoagulant contraindication exists. The optimal duration of prophylaxis is not
      known, but 14 days was used in recent studies. CONCLUSIONS: Prophylaxis of VTE in
      acutely ill medical inpatients is underused. Data provide some guidance for
      increasing awareness and optimizing patient care.

PMID- 15941824
TI  - Impaired parasympathetic response to feeding in ventilated preterm babies.
AB  - BACKGROUND: Premature very low birthweight (VLBW) infants are born with an
      underdeveloped parasympathetic nervous system (PNS) which may limit their ability
      to respond adequately to feeding and may limit their capacities for extrauterine
      growth and development. OBJECTIVES: To describe the patterns of autonomic
      response to feeding and identify relationships between change in heart period
      variability measures over time with selected infant characteristics. METHODS:
      Individual growth curve analysis techniques were used to describe the patterns of
      change over time in sympathetic and parasympathetic tone as measured by low and
      high frequency heart period power. RESULTS: Sixteen mechanically ventilated VLBW
      infants with a mean corrected gestational age of 30.4 weeks participated in the
      study. The low frequency (LF) power slope was -17.67 (p = 0.0002) and the high
      frequency (HF) power slope was -0.92 (0.0003). There was a significant
      relationship between HF slope and birth gestational age (r = -0.49, p = 0.05).
      CONCLUSIONS: HF power, representing primarily parasympathetic activity, did not
      increase with enteral feeding as anticipated. LF power, an indicator of
      sympathetic tone, decreased during and after feeding suggesting the anticipated
      effect of inhibition of the sympathetic nervous system in response to the gut
      stimulus. Critically ill VLBW infants possess an overriding sympathetic response,
      but may not have adequate PNS tone development.

PMID- 15941825
TI  - Incidence of nasal trauma associated with nasal prong versus nasal mask during
      continuous positive airway pressure treatment in very low birthweight infants: a
      randomised control study.
AB  - OBJECTIVE: To compare the incidence of nasal trauma associated with the use of
      prong or mask during nasal continuous positive airway pressure (nCPAP) support in
      very low birthweight (<1501 g) infants. DESIGN: Randomised controlled clinical
      trial. SETTING: Tertiary care university hospital, Department of Paediatrics,
      Kuala Lumpur, Malaysia. METHODS: All very low birthweight infants admitted to the
      neonatal intensive care unit between July 2001 and December 2003 who received
      nCPAP through the Infant Flow Driver were randomised to the use of either nasal
      prong or mask. The nasal cavity of these infants was inspected daily during the
      first week and then weekly until they were weaned off nCPAP. RESULTS: Of the 89
      infants recruited, 41 were randomised to the mask group and 48 to the prong
      group. There was no significant difference in the incidence of nasal trauma
      between the two groups (p = 0.5). The primary site of trauma was at the junction
      between the nasal septum and the philtrum in infants in the mask group and the
      walls of the nasal septum in the prong group. Logistic regression analysis showed
      that duration of nCPAP was the only significant risk factor associated with
      development of nasal injury, after birth weight, gestational age, and nasal
      device used had been controlled for (adjusted odds ratio 1.04; 95% confidence
      interval 1.01 to 1.07; p = 0.003). CONCLUSION: Irrespective of the type of nasal
      device used, nasal trauma is common during nCPAP treatment, which should
      therefore be terminated as soon as possible.

PMID- 15941826
TI  - Ventilation strategies and outcome in randomised trials of high frequency
      ventilation.
AB  - OBJECTIVE: Randomised controlled trials comparing elective use of high frequency
      ventilation (HFV) with conventional mechanical ventilation (CMV) in preterm
      infants have yielded conflicting results. We hypothesised that the variability of
      results may be explained by differences in study design, ventilation strategies,
      delay in initiation of HFV, and use of permissive hypercapnia. METHODS:
      Randomised controlled trials comparing the elective use of HFV with any form of
      CMV were identified. Trials were classified according to the ventilation
      strategies used for HFV and CMV and oscillator device employed. For cumulative
      meta-analyses, trials were arranged by the following covariables: mean duration
      until randomisation, Paco(2) limits, publication date, and sample size. Odds
      ratios (OR) and 95% confidence intervals were calculated using fixed and random
      effects models. RESULTS: Seventeen randomised trials enrolling 3776 patients were
      included. Unlike previous meta-analyses, there was no significant difference in
      the incidence of bronchopulmonary dysplasia or death (OR 0.87, 0.75-1.00) and
      severe intraventricular haemorrhage grade 3-4 (1.14, 0.96-1.37). The incidence of
      air leaks (OR 1.23, 1.06-1.44) was significantly increased with HFV. Subgroup
      analyses and cumulative meta-analyses demonstrated that trial results were
      related to the ventilation strategies used for HFV and CMV. No influence was
      found for mean time to randomisation, degree of permissive hypercapnia, or sample
      size. CONCLUSIONS: Heterogeneity among trials of elective HFV compared to CMV in
      preterm infants is mainly due to differences in ventilatory strategies.
      Optimising CMV strategy appeared to be as effective as using HFV in improving
      pulmonary outcome in preterm infants.

PMID- 15941827
TI  - Prehistoric contacts over the Straits of Gibraltar indicated by genetic analysis
      of Iberian Bronze Age cattle.
AB  - The geographic situation of the Iberian Peninsula makes it a natural link between
      Europe and North Africa. However, it is a matter of debate to what extent African
      influences via the Straits Gibraltar have affected Iberia's prehistoric
      development. Because early African pastoralist communities were dedicated to
      cattle breeding, a possible means to detect prehistoric African-Iberian contacts
      might be to analyze the origin of cattle breeds on the Iberian Peninsula. Some
      contemporary Iberian cattle breeds show a mtDNA haplotype, T1, that is
      characteristic to African breeds, generally explained as being the result of the
      Muslim expansion of the 8th century A.D., and of modern imports. To test a
      possible earlier African influence, we analyzed mtDNA of Bronze Age cattle from
      the Portalon cave at the Atapuerca site in northern Spain. Although the majority
      of samples showed the haplotype T3 that dominates among European breeds of today,
      the T1 haplotype was found in one specimen radiocarbon dated 1800 calibrated
      years B.C. Accepting T1 as being of African origin, this result indicates
      prehistoric African-Iberian contacts and lends support to archaeological finds
      linking early African and Iberian cultures. We also found a wild ox haplotype in
      the Iberian Bronze Age sample, reflecting local hybridization or backcrossing or
      that aurochs were hunted by these farming cultures.

PMID- 15941828
TI  - Global and Hox-specific roles for the MLL1 methyltransferase.
AB  - The mixed-lineage leukemia (MLL1/ALL-1/HRX) histone methyltransferase is involved
      in the epigenetic maintenance of transcriptional memory and the pathogenesis of
      human leukemias. To understand its role in cell type specification, we determined
      the human genomic binding sites of MLL1. We found that MLL1 functions as a human
      equivalent of yeast Set1. Like Set1, MLL1 localizes with RNA polymerase II (Pol
      II) to the 5' end of actively transcribed genes, where histone H3 lysine 4
      trimethylation occurs. Consistent with this global role in transcription, MLL1
      also localizes to microRNA (miRNA) loci that are involved in leukemia and
      hematopoiesis. In contrast to the 5' proximal binding behavior at most protein
      coding genes, MLL1 occupies an extensive domain within a transcriptionally active
      region of the HoxA cluster. The ability of MLL1 to serve as a start site-specific
      global transcriptional regulator and to participate in larger chromatin domains
      at the Hox genes reveals dual roles for MLL1 in maintenance of cellular identity.

PMID- 15941829
TI  - Gelatinase A and membrane-type matrix metalloproteinases 1 and 2 are responsible
      for follicle rupture during ovulation in the medaka.
AB  - Identification of the hydrolytic enzymes involved in follicle rupture during
      vertebrate ovulation remains a central challenge for research in reproductive
      biology. Here, we report a previously uncharacterized approach to this problem by
      using an in vitro ovulation system in the medaka, Oryzias latipes, which is a
      small freshwater teleost. We found that follicle rupture in the medaka ovary
      involves the cooperation of at least three matrix metalloproteinases (MMPs),
      together with the tissue inhibitor of metalloproteinase-2b protein. We determined
      the discrete roles of each of these proteins during follicle rupture. Our results
      indicated that gelatinase A induces the hydrolysis of type IV collagen
      constituting the basement membrane, membrane-type 2 MMP degrades type I collagen
      present in the theca cell layer, and MT1-MMP and the tissue inhibitor of
      metalloproteinase-2b are involved in the production and regulation of gelatinase
      A. These findings will help clarify the mechanism of follicle wall degradation
      during ovulation in mammalian species.

PMID- 15941830
TI  - Signal peptide-chaperone interactions on the twin-arginine protein transport
      pathway.
AB  - The twin-arginine transport (Tat) system is a protein-targeting pathway of
      prokaryotes and chloroplasts. Most Escherichia coli Tat substrates are complex
      metalloenzymes that must be correctly folded and assembled before transport, and
      a preexport chaperone-mediated "proofreading" process is therefore in operation.
      The paradigm proofreading chaperone is TorD, which coordinates maturation and
      export of the key respiratory enzyme trimethylamine N-oxide reductase (TorA). It
      is demonstrated here that purified TorD binds tightly and with exquisite
      specificity to the TorA twin-arginine signal peptide in vitro. It is also
      reported that the TorD family constitutes a hitherto unexpected class of
      nucleotide-binding proteins. The affinity of TorD for GTP is enhanced by initial
      signal peptide binding, and it is proposed that GTP governs signal peptide
      binding-and-release cycles during Tat proofreading.

PMID- 15941831
TI  - Development of a unique system for spatiotemporal and lineage-specific gene
      expression in mice.
AB  - We have developed an advanced method for conditional gene expression in mice that
      integrates the Cre-mediated and tetracycline-dependent expression systems. An
      rtTA gene, preceded by a loxP-flanked STOP sequence, was inserted into the ROSA26
      locus to create a R26STOPrtTA mouse strain. When the STOP sequence is excised by
      Cre-mediated recombination, the rtTA is expressed in the Cre-expressing cells and
      all of their derivatives. Therefore, cell type-, tissue-, or lineage-specific
      expression of rtTA is achieved by the use of an appropriate Cre transgenic
      strain. In mice also carrying a target gene under the control of the tetracycline
      response element, inducible expression of the target gene is temporally regulated
      by administration of doxycycline. Our results demonstrate that this universal
      system is uniquely suited for spatiotemporal and lineage-specific gene expression
      in an inducible fashion. Gene expression can be manipulated in specific cell
      types and lineages with a flexibility that is difficult to achieve with
      conventional methods.

PMID- 15941832
TI  - HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor
      without involving 7SK RNA and positive transcription elongation factor b.
AB  - The HEXIM1 protein has been shown to form a protein-RNA complex composed of 7SK
      small nuclear RNA and positive transcription elongation factor b (P-TEFb), which
      is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1, and to inhibit the
      kinase activity of CDK9, thereby suppressing RNA polymerase II-dependent
      transcriptional elongation. Here, we biochemically demonstrate that HEXIM1 forms
      a distinct complex with glucocorticoid receptor (GR) without RNA, CDK9, or cyclin
      T1. HEXIM1, through its arginine-rich nuclear localization signal, directly
      associates with the ligand-binding domain of GR. Introduction of HEXIM1 short
      interfering RNA and adenovirus-mediated exogenous expression of HEXIM1 positively
      and negatively modulated glucocorticoid-responsive gene activation, respectively.
      In the nucleus, HEXIM1 was shown to localize in a distinct compartment from that
      of the p160 coactivator transcriptional intermediary factor 2. Overexpression of
      HEXIM1 decreased ligand-dependent association between GR and transcriptional
      intermediary factor 2. Antisense-mediated disruption of 7SK blunted the negative
      effect of HEXIM1 on arylhydrocarbon receptor-dependent transcription but not on
      GR-mediated one, indicating that a class of transcription factors are direct
      targets of HEXIM1. These results indicate that HEXIM1 has dual roles in
      transcriptional regulation: inhibition of transcriptional elongation dependent on
      7SK RNA and positive transcription elongation factor b and interference with the
      sequence-specific transcription factor GR via a direct protein-protein
      interaction. Moreover, the fact that the central nuclear localization signal of
      HEXIM1 is essential for both of these actions may argue the crosstalk of these
      functions.

PMID- 15941833
TI  - Endothelial dihydrofolate reductase: critical for nitric oxide bioavailability
      and role in angiotensin II uncoupling of endothelial nitric oxide synthase.
AB  - Recent studies demonstrate that oxidative inactivation of tetrahydrobiopterin
      (H4B) may cause uncoupling of endothelial nitric oxide synthase (eNOS) to produce
      superoxide (O2*-). H4B was found recyclable from its oxidized form by
      dihydrofolate reductase (DHFR) in several cell types. Functionality of the
      endothelial DHFR, however, remains completely unknown. Here we present findings
      that specific inhibition of endothelial DHFR by RNA interference markedly reduced
      endothelial H4B and nitric oxide (NO.) bioavailability. Furthermore, angiotensin
      II (100 nmol/liter for 24 h) caused a H4B deficiency that was mediated by H2O2
      dependent down-regulation of DHFR. This response was associated with a
      significant increase in endothelial O2*- production, which was abolished by eNOS
      inhibitor N-nitro-L-arginine-methyl ester or H2O2 scavenger polyethylene glycol
      conjugated catalase, strongly suggesting H2O2-dependent eNOS uncoupling. Rapid
      and transient activation of endothelial NAD(P)H oxidases was responsible for the
      initial burst production of O2* (Rac1 inhibitor NSC 23766 but not an N-nitro-L
      arginine-methyl ester-attenuated ESR O2*- signal at 30 min) in response to
      angiotensin II, preceding a second peak in O2*- production at 24 h that
      predominantly depended on uncoupled eNOS. Overexpression of DHFR restored NO.
      production and diminished eNOS production of O2*- in angiotensin II-stimulated
      cells. In conclusion, these data represent evidence that DHFR is critical for H4B
      and NO. bioavailability in the endothelium. Endothelial NAD(P)H oxidase-derived
      H2O2 down-regulates DHFR expression in response to angiotensin II, resulting in
      H4B deficiency and uncoupling of eNOS. This signaling cascade may represent a
      universal mechanism underlying eNOS dysfunction under pathophysiological
      conditions associated with oxidant stress.

PMID- 15941834
TI  - Increase of sympathetic outflow measured by neuropeptide Y and decrease of the
      hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus
      erythematosus and rheumatoid arthritis: another example of uncoupling of response
      systems.
AB  - OBJECTIVE: To study in parallel the outflow of the sympathetic nervous system
      (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus
      erythematosus (SLE) and rheumatoid arthritis (RA). METHODS: 32 patients with SLE,
      62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of
      the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide
      Y (NPY) was used to evaluate the sympathetic outflow. RESULTS: Patients with SLE
      had increased NPY levels in comparison with HS, irrespective of prior
      prednisolone treatment (p<0.001). For patients with RA, only those with
      prednisolone treatment had increased NPY levels in comparison with HS (p =
      0.016). Daily prednisolone dose correlated positively with serum NPY in RA
      (R(Rank) = 0.356, p = 0.039). In contrast, plasma ACTH levels were generally
      decreased significantly in comparison with HS in SLE with prednisolone, and in RA
      with/without prednisolone. Similarly, serum cortisol levels were also decreased
      in SLE with/without prednisolone, and in RA with prednisolone. The NPY/ACTH ratio
      was increased in SLE and RA, irrespective of prior prednisolone treatment. The
      NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with
      prednisolone. Twelve weeks' anti-TNF antibody treatment with adalimumab did not
      decrease NPY levels in RA, irrespective of prednisolone treatment. CONCLUSIONS:
      An increased outflow of the SNS was shown and a decreased tone of the HPA axis in
      patients with SLE and RA. Low levels of cortisol in relation to SNS
      neurotransmitters may be proinflammatory because cooperative anti-inflammatory
      coupling of the two endogenous response axes is missing.

PMID- 15941835
TI  - Interobserver reliability in musculoskeletal ultrasonography: results from a
      "Teach the Teachers" rheumatologist course.
AB  - OBJECTIVE: To assess the interobserver reliability of the main periarticular and
      intra-articular ultrasonographic pathologies and to establish the principal
      disagreements on scanning technique and diagnostic criteria between a group of
      experts in musculoskeletal ultrasonography. METHODS: The shoulder, wrist/hand,
      ankle/foot, or knee of 24 patients with rheumatic diseases were evaluated by 23
      musculoskeletal ultrasound experts from different European countries randomly
      assigned to six groups. The participants did not reach consensus on scanning
      method or diagnostic criteria before the investigation. They were unaware of the
      patients' clinical and imaging data. The experts from each group undertook a
      blinded ultrasound examination of the four anatomical regions. The ultrasound
      investigation included the presence/absence of joint effusion/synovitis, bony
      cortex abnormalities, tenosynovitis, tendon lesions, bursitis, and power Doppler
      signal. Afterwards they compared the ultrasound findings and re-examined the
      patients together while discussing their results. RESULTS: Overall agreements
      were 91% for joint effusion/synovitis and tendon lesions, 87% for cortical
      abnormalities, 84% for tenosynovitis, 83.5% for bursitis, and 83% for power
      Doppler signal; kappa values were good for the wrist/hand and knee (0.61 and
      0.60) and fair for the shoulder and ankle/foot (0.50 and 0.54). The principal
      differences in scanning method and diagnostic criteria between experts were
      related to dynamic examination, definition of tendon lesions, and pathological v
      physiological fluid within joints, tendon sheaths, and bursae. CONCLUSIONS:
      Musculoskeletal ultrasound has a moderate to good interobserver reliability.
      Further consensus on standardisation of scanning technique and diagnostic
      criteria is necessary to improve musculoskeletal ultrasonography reproducibility.

PMID- 15941836
TI  - Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis?
AB  - OBJECTIVES: To study which cut off point of DAS28 corresponds to fulfilment of
      the American Rheumatism Association (ARA) preliminary remission criteria, and
      clinical remission criteria in patients with rheumatoid arthritis (RA). METHODS:
      All adult patients diagnosed with RA at Jyvaskyla Central Hospital 1997-98 were
      assessed for remission at 5 years. Remission was defined as (a) ARA remission;
      (b) clinical remission (defined as no tender or swollen joints and normal
      erythrocyte sedimentation rate). DAS28 was used to measure disease activity. A
      receiver operating characteristics curve analysis was performed to calculate a
      cut off point of DAS28 that best corresponds to the ARA remission criteria and
      the clinical remission criteria. RESULTS: 161 patients (mean age 57 years, 107
      (66%) female, 98 (61%) with positive rheumatoid factor, and 51 (32%) with
      erosions) were studied. At 5 years, 19 (12%) patients met the ARA remission
      criteria, and 55 (34%) met the clinical remission criteria. The cut off value of
      DAS28 was 2.32 for the ARA remission criteria, and 2.68 for the clinical
      remission criteria. In patients with DAS28 <2.32, 11/57 (19%) had tender joints,
      6/57 (11%) had swollen joints, and 4/57 (7%) had both tender and swollen joints
      (66 joint count). CONCLUSION: In this study the DAS28 cut off point for the ARA
      remission was lower than in previous studies. The cut off point for DAS28
      remission remains controversial. A substantial proportion of patients below the
      DAS28 cut off point for remission have tender or swollen joints, or both. DAS28
      may not be an appropriate tool for assessment of remission in RA.

PMID- 15941837
TI  - Problem of the atherothrombotic potential of non-steroidal anti-inflammatory
      drugs.
AB  - Treatment of pain in rheumatoid arthritis must take into account the
      gastrointestinal and cardiovascular risk of individual patients. Adequate results
      are not yet available, and until they are, treatment recommendations must take
      into account, not only the more favourable gastrointestinal risk profile of
      selective COX-2 inhibitors, but also the potential atherothrombotic risk of any
      NSAID or selective COX-2 inhibitor treatment.

PMID- 15941838
TI  - Intracellular and extracellular CPPD crystals are a regular feature in synovial
      fluid from uninflamed joints of patients with CPPD related arthropathy.
AB  - OBJECTIVES: To determine whether calcium pyrophosphate dihydrate (CPPD) crystals
      can be found in the synovial fluid of non-inflamed joints in patients with CPPD
      related arthropathy; if so, to determine whether they interact with cells and
      produce subclinical inflammation in this setting. METHODS: 74 synovial fluid
      samples were obtained from non-inflamed knees of 74 patients with CPPD related
      arthropathy. Identification of CPPD crystals and synovial fluid cell counts were
      done manually in undiluted samples using a haematocytometric chamber. A
      supravital stain (Testsimplets, Boehringer Mannheim) was used to carry out
      differential counts and to assess the presence of intracellular crystals.
      RESULTS: All 74 samples contained CPPD crystals. The mean cell count was 301.4
      cells/microl (95% confidence interval (CI), 216.6 to 386.4; range 22 to 2302.5).
      Mononuclear cells accounted for 83.2% (95% CI, 80.4% to 86.1%; range 43% to 99%),
      the rest being polymorphonuclear (PMN) cells (16.8% (95% CI, 13.9% to 19.6%;
      range 1% to 57%)). All the samples contained intracellular CPPD crystals, which
      were found in 24.0% of all the cells (95% CI, 20.1% to 27.9%; range 1% to 78%).
      Most of the intracellular crystals were inside mononuclear cells (22.2% of all
      the cells (95% CI, CI 18.5% to 25.9%)), although some PMN also contained them
      (1.8% of all the cells (95% CI, 1.1% to 2.4%)). CONCLUSIONS: CPPD crystals are
      normally found in synovial fluid of non-inflamed joints of patients with CPPD
      related arthropathy, and they interact with cells. The raised cell counts and
      percentage of PMN suggest mild subclinical inflammation in these joints.

PMID- 15941839
TI  - Low circulating soluble interleukin 2 receptor level predicts rapid response in
      patients with refractory rheumatoid arthritis treated with infliximab.
AB  - BACKGROUND: Treatment with infliximab induces a rapid therapeutic response in
      most patients with active rheumatoid arthritis. Factors predicting good response
      are not well known. OBJECTIVE: To study the predictive value of baseline level of
      soluble interleukin 2 receptor (sIL2R), a marker of lymphocyte activation, on the
      treatment response. METHODS: 24 patients with active rheumatoid arthritis
      received intravenous infusions of infliximab at study entry, at two weeks, at six
      weeks, and at eight week intervals thereafter. Outcome was evaluated at six weeks
      and 22 weeks. Clinical assessment and standard laboratory tests were made and the
      DAS28 disease activity score was calculated. Serum sIL2R level at entry was
      measured by automated immunoassay analyser (Immulite). The mean change in DAS28
      score from entry to six weeks and 22 weeks was calculated and related to sIL2R
      level using baseline adjusted robust regression analysis. RESULTS: Baseline level
      of serum sIL2R (mean (SD), 621 (325) U/ml) did not correlate with baseline DAS28
      score (r = 0.24 (95% confidence interval, -0.18 to 0.58)). At six weeks DAS28
      scores improved, with a mean change of -2.53 (-3.08 to -1.98) (p<0.001). This
      change was predicted by low baseline sIL2R level (regression coefficient per 100
      U/ml: 0.205 (0.003 to 0.407) (p = 0.047)). At 22 weeks the DAS28 scores improved,
      with a mean change of -2.26 (-2.75 to -1.77) (p<0.001). The change was not
      predicted by baseline sIL2R level. CONCLUSIONS: Low baseline sIL2R level may
      predict a rapid clinical response in patients with refractory rheumatoid
      arthritis treated with infliximab.

PMID- 15941840
TI  - Confirmation of GPRA: a putative drug target for asthma.

PMID- 15941841
TI  - Are some people not safer after successful treatment of tuberculosis?

PMID- 15941842
TI  - Sleepiness and neurodegeneration in sleep-disordered breathing: convergence of
      signaling cascades.

PMID- 15941843
TI  - Statement on home care for patients with respiratory disorders.

PMID- 15941844
TI  - Reduction in plasma free fatty acid in patients with chronic obstructive
      pulmonary disease.

PMID- 15941845
TI  - Successful treatment of hypercalcemia with cinacalcet in renal transplant
      recipients with persistent hyperparathyroidism.
AB  - BACKGROUND: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary
      and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not
      been examined in renal transplant patients with persistent hyperparathyroidism.
      The aim of this study was to evaluate the effect of cinacalcet as a novel therapy
      for the management of such patients. METHODS: Eleven renal allograft recipients
      with persistent hyperparathyroidism were treated with cinacalcet. The total study
      time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum
      calcium in the predefined normal target range of 2.10-2.60 mmol/l. RESULTS: Serum
      calcium decreased significantly from 2.73+/-0.05 mmol/l to 2.44+/-0.05 and 2.42+/
      0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients
      reached the target range rapidly and remained normocalcaemic throughout the
      study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10,
      respectively, compared with week 0. Serum phosphate increased. Renal function
      remained stable and no allograft rejection was observed. From weeks 2 to 10,
      daily cinacalcet doses administered were 30 mg (n = 8), 15 mg (n = 1) and 60 mg
      (n = 1), respectively. CONCLUSION: Cinacalcet was effective in correcting the
      hypercalcaemia associated with persistent hyperparathyroidism after renal
      transplantation. It appears to be safe. Thus, cinacalcet represents a promising
      alternative for parathyroidectomy in these patients.

PMID- 15941846
TI  - The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients
      with persistent hyperparathyroidism.
AB  - BACKGROUND: Treatment of persistent hyperparathyroidism in renal transplant
      patients resistant to calcium and vitamin D sterols is limited and often requires
      parathyroidectomy. Given the potential hazards linked to surgery, an alternative
      approach to manage excess parathyroid hormone (PTH) secretion is needed.
      Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in
      the parathyroid. Lowering of the serum calcium concentration with the
      calcimimetic cinacalcet has previously been demonstrated in patients with primary
      hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we
      present the first clinical observations of a calcimimetic in patients with
      persistent hyperparathyroidism. METHODS: A 30 mg dose of cinacalcet was
      prescribed once daily for 3 months to seven female and seven male stable renal
      transplant patients, aged 23-65 years, 7 months to 14 years after
      transplantation, with a serum creatinine ranging from 89 to 229 micromol/l and
      persistent hyperparathyroidism. Concomitant medication included cyclosporin and
      low-dose prednisone in all patients. RESULTS: On cinacalcet, serum calcium
      decreased and normalized in all but two patients (baseline 2.72+/-0.03 mmol/l; 1
      month 2.42+/-0.04 mmol/l, P<0.001), whereas serum PTH and phosphate levels did
      not change significantly. A slight reduction in renal function, as assessed by
      serum creatinine concentration, was observed at months 2 and 3 (P<0.05). An
      immunoglobulin-deficient patient developed colitis after 1 week of treatment and
      cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed
      side effects. CONCLUSION: Calcimimetics are a promising therapy in renal
      transplant patients with persistent hyperparathyroidism. Prospective controlled
      studies must now be designed focusing on functionally relevant musculo-skeletal
      end-points and allowing the exclusion of negative effects on long-term renal and
      general outcome of such patients.

PMID- 15941847
TI  - Toll-like receptors recognize uropathogenic Escherichia coli and trigger
      inflammation in the urinary tract.

PMID- 15941848
TI  - Renal juxtaglomerular apparatus hyperplasia.

PMID- 15941849
TI  - Ovarian transplantation between monozygotic twins discordant for premature
      ovarian failure.
AB  - Monozygotic 24-year-old twins presented with discordant ovarian function. One had
      had premature ovarian failure at the age of 14 years, whereas her sister had
      normal ovaries and three naturally conceived children. After unsuccessful egg
      donation therapy, the sterile twin received a transplant of ovarian cortical
      tissue from her sister by means of a minilaparotomy. Within three months after
      transplantation, the recipient's cycles resumed and serum gonadotropin levels
      fell to the normal range. During the second cycle, she conceived, and her
      pregnancy progressed uneventfully. At 38 weeks' gestation, she delivered a
      healthy-appearing female infant.

PMID- 15941850
TI  - The gene encoding fibrinogen-beta is a target for retinoic acid receptor-related
      orphan receptor alpha.
AB  - Fibrinogen is a plasma protein synthesized by the liver. It is composed of three
      chains (alpha, beta, gamma). In addition to its main function as a coagulation
      factor, this acute phase protein is also a risk marker for atherosclerosis.
      Retinoic acid receptor-related orphan receptor (ROR)alpha is a nuclear receptor
      modulating physiopathological processes such as cerebellar ataxia, inflammation,
      atherosclerosis, and angiogenesis. In this study, we identified RORalpha as a
      regulator of fibrinogen-beta gene expression in human hepatoma cells and in mouse
      liver. A putative RORalpha response element (RORE) was identified in the human
      fibrinogen-beta promoter. EMSA showed that RORalpha binds specifically to this
      RORE, and cotransfection experiments in HepG2 hepatoma cells indicated that this
      RORE confers RORalpha-dependent transcriptional activation to both the human
      fibrinogen-beta and the thymidine kinase promoters. Stable transfection
      experiments in HepG2 and Hep3B hepatoma cells demonstrated that overexpression of
      RORalpha specifically increases endogenous fibrinogen-beta mRNA levels. Chromatin
      immunoprecipitation experiments revealed that the fibrinogen-beta RORE is
      occupied by RORalpha in HepG2 cells. Thus, the human fibrinogen-beta gene is a
      direct target for RORalpha. Furthermore, fibrinogen-beta mRNA levels in liver and
      plasma fibrinogen concentrations are specifically decreased in staggerer mice,
      which are homozygous for a deletion invalidating the Rora gene. Taken together,
      these data add further evidence for an important role of RORalpha in the control
      of liver gene expression with potential pathophysiological consequences on
      coagulation and cardiovascular risk.

PMID- 15941851
TI  - Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine
      functions.
AB  - Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple
      roles in mammalian development and homeostasis. We previously reported that, in
      human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide,
      which are typical environmental contaminants and cause masculinization in female
      mollusks, are potent stimulators of human chorionic gonadotropin production and
      aromatase activity, which play key endocrine functions in maintaining pregnancy
      and fetal development. However, the molecular mechanism through which these
      compounds stimulate these endocrine functions remains unclear. Our current study
      shows that trialkyltin compounds, including tributyltin chloride and triphenyltin
      hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand
      binding domain of RXR with high affinity and function as transcriptional
      activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of
      trialkyltins is RXR specific and does not activate the retinoic acid receptor
      pathway. In addition, trialkyltins activate RXR to stimulate the expression of a
      luciferase reporter gene containing the human placental promoter I.1 sequence of
      aromatase, suggesting that trialkyltins stimulate human placental endocrine
      functions through RXR-dependent signaling pathways. Therefore, our results
      suggest that activation of RXR may be a novel mechanism by which trialkyltins
      alter human endocrine functions.

PMID- 15941852
TI  - Modulator recognition factor 1, an AT-rich interaction domain family member, is a
      novel corepressor for estrogen receptor alpha.
AB  - Cardiovascular tissues are important targets of estrogen action. Vascular cells
      express the two known estrogen receptors (ERs), ERalpha and ERbeta, ligand
      activated transcription factors that regulate gene transcription through
      interactions with both coactivator and corepressor molecules. To isolate ERalpha
      coregulators in vascular cells, we performed a yeast two-hybrid screen for
      ERalpha-interacting proteins using a human aorta library. Here we report the
      identification of modulator recognition factor 1 (MRF1) as an ERalpha-interacting
      corepressor protein. Full-length MRF1 binds to both the N terminus and the C
      terminus of ERalpha. ERalpha and MRF1 coimmunoprecipitate in an estradiol
      independent manner, and recombinant ERalpha binds to both full-length and COOH
      terminal MRF1 in the absence of estradiol. MRF1 also interacts in a ligand
      dependent manner with thyroid receptor alpha, retinoid X receptor alpha, and
      androgen receptor, and in a ligand-independent manner with ERbeta and the
      retinoic acid receptor. MRF1 RNA is highly expressed in aorta, heart, skeletal
      muscle, and liver. MRF1 has intrinsic repressor activity in an in vitro GAL
      reporter assay. Transient transfection studies show that MRF1 represses
      transcription by ERalpha activated by estradiol in a dose-dependent manner, as
      well as by the selective ER modulators 4-hydroxy-tamoxifen and raloxifene. MRF1
      repression is not influenced by pharmacological inhibition of histone
      deacetylase. These data identify MRF1 as a repressor of ERalpha-mediated
      transcriptional activation and support a role for MRF1 in regulating ER-dependent
      gene expression in cardiovascular and other cells.

PMID- 15941853
TI  - Knockout of luteinizing hormone receptor abolishes the effects of follicle
      stimulating hormone on preovulatory maturation and ovulation of mouse graafian
      follicles.
AB  - It is considered a dogma that a secretory peak of LH is indispensable as the
      trigger of ovulation. However, earlier studies on hypophysectomized rodents have
      shown that stimulation with recombinant FSH, devoid of any LH activity, is able
      to boost the final stages of follicular maturation and trigger ovulation. As the
      expression of ovarian LH receptors (LHRs) still persists after hypophysectomy,
      such studies cannot totally exclude the possibility that LHR activation is
      involved in the apparently pure FSH effects. To revisit this question, we
      analyzed in LHR knockout (LuRKO) mice the progression of folliculogenesis and
      induction of ovulation by human chorionic gonadotropin and human recombinant FSH
      treatments. The results provide clear evidence that follicular development and
      ovulation could not be induced by high doses of FSH in the absence of LHR
      expression. Ovarian histology and oocyte analyses indicated that follicular
      maturation did not advance in LuRKO mice beyond the antral follicle stage.
      Neither were ovulations detected in LuRKO ovaries after any of the gonadotropin
      treatments. The ovarian resistance to FSH treatment in the absence of LHR was
      confirmed by real-time RT-PCR and immunohistochemical analyses of a number of
      gonadotropin-dependent genes, which only responded to the treatments in wild-type
      control mice. Negative findings were not altered by estradiol priming preceding
      the gonadotropin stimulations. Hence, the present study shows that, in addition
      to ovulation, the expression of LHR is essential for follicular maturation in the
      progression from antral to preovulatory stage.

PMID- 15941854
TI  - Clonal heterogeneity in growth kinetics of CD34+CD38- human cord blood cells in
      vitro is correlated with gene expression pattern and telomere length.
AB  - Human hematopoietic stem cells (HSCs) are characterized by an extensive
      proliferative capacity that decreases from fetal liver to cord blood (CB) to
      adult bone marrow. In previous studies, it was demonstrated that the
      proliferative capacity of individual CD34+CD38- HSC clones is correlated with
      their growth kinetics in vitro and that HSC turnover in vivo can be estimated by
      telomere-length measurements. The present study was aimed at the characterization
      of the clonal composition of CD34+CD38- human umbilical CB cells in terms of
      growth kinetics, telomere length, and gene expression profile. For this purpose,
      individual CD34+CD38- CB cells were sorted into 96-well plates containing serum
      free medium supplemented with six growth factors. During expansion, cell numbers
      in each individual well were scored in 3-day intervals. Once sufficient cell
      numbers were achieved, telomere length was measured by flow fluorescence in situ
      hybridization (flow FISH). In a second set of experiments, gene expression and
      colony-forming capacity were analyzed in slowly growing clones as compared with
      fast-growing clones, using linear amplification and oligonucleotide microarrays
      (HG-U133A; Affymetrix). Individual CD34+CD38- cells from CB displayed an
      extensive functional heterogeneity in growth kinetics. Among highly proliferative
      clones, the most slowly growing clones were characterized by the longest
      telomeres. Furthermore, significant differences in gene expression were detected
      between slow- and fast-growing clones, whereas no significant difference in
      colony-forming capacity was observed. These data provide further evidence for a
      functional hierarchy in the human HSC compartment and suggest a link between
      telomere length and proliferation capacity of individual HSC clones.

PMID- 15941855
TI  - Polyamine depletion reduces TNFalpha/MG132-induced apoptosis in bone marrow
      stromal cells.
AB  - Polyamines are powerful modulators of both growth and survival in mammalian
      cells. In this study, we investigated the possibility of attenuating the process
      of apoptosis in bone marrow stromal cells (BMSCs), which comprise mesenchymal
      stem cells, by reducing the intracellular levels of polyamines. BMSCs were
      isolated from rat femurs and expanded for 12 days. At this time, BMSCs were
      CD34neg, CD45neg, and mostly CD90pos. BMSCs were grown for an additional 2 days
      in the presence of 1 mM alpha-difluoromethylornithine (DFMO), an inhibitor of
      ornithine decarboxylase, which reduced the content of both putrescine and
      spermidine by nearly 90%. DFMO treatment progressively slowed down BMSC
      proliferation, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazoliumbromide (MTT) assay, without arresting their growth
      completely. The effect of polyamine depletion on caspase-3 activity was evaluated
      in BMSCs after treatment with 500 U/ml tumor necrosis factor-alpha (TNFalpha) and
      5 microM MG132, an inhibitor of proteasome. Caspase-3 activity increased linearly
      over a period of 24-hour stimulation (p<.01), but this augmentation was blunted
      by 50% after DFMO administration (p<.05). The effect of DFMO on TNFalpha/MG132
      induced upregulation of caspase-3 activity was reversed by the addition of 100
      microM putrescine, confirming that polyamines were really involved in the
      apoptotic process. Also, the number of apoptotic BMSCs after TNFalpha/MG132
      treatment, as determined by terminal transferase-mediated dUTP nick end-labeling
      (TUNEL) assay, were threefold reduced after polyamine depletion (p<.05). On the
      contrary, DFMO did not affect the MG132-mediated increase in p53 abundance, nor
      its translocation to the nucleus. Thus, polyamine depletion can be considered a
      useful tool for counteracting programmed cell death in BMSCs without involving
      the p53 proapoptotic protein.

PMID- 15941856
TI  - Abnormal development of mouse embryoid bodies lacking p27Kip1 cell cycle
      regulator.
AB  - Cultures of three-dimensional aggregates of embryonic stem cells (ESCs) called
      embryoid bodies (EBs) provide a valuable system for analyzing molecular
      mechanisms that regulate differentiation of this unique cell type. Cyclin
      dependent kinase inhibitor p27Kip1 (p27) becomes elevated during the
      differentiation of mouse ESCs (mESCs). In this study, various aspects of
      differentiation of EBs produced from normal and p27-deficient mESCs were analyzed
      to address the biological significance of this elevation. It was found that EBs
      lacking p27 grew significantly bigger, but this was not accompanied by detect
      able abnormalities in the activities of cyclin-dependent kinases (CDKs). In most
      EB cells, downregulation of activating cyclins rather than upregulation of
      inhibiting p27 is probably responsible for lowering the activity of their CDKs.
      Abnormalities in the development of specific cell lineages were also observed in
      p27-deficient EBs. These included elimination of cells positive for cytokeratin
      endo-A (TROMA-I) and increased proliferation and formation of cavities
      originating from cells positive for Lewis-X. Our data also suggest that although
      two different pools of Lewis-X-expressing cells, cluster forming (ESC-like) and
      cavity forming (neural progenitors), normally exist in EBs, the absence of p27
      leads to the enhancement of only the neural pool. No failure was found when the
      neurogenic capacity of p27-deficient mESCs was tested using various protein
      markers. Together, our data point to a dual role of p27 in mESCs, with one role
      being in the regulation of proliferation and the other role in establishing some
      other aspects of a differentiated phenotype.

PMID- 15941858
TI  - Isolation and characterization of neurogenic mesenchymal stem cells in human
      scalp tissue.
AB  - Recent studies have shown that adult tissues contain stem/ progenitor cells
      capable of not only generating mature cells of their tissue of origin but also
      transdifferentiating themselves into other tissue cells. Murine skin-derived
      precursor cells, for example, have been described as unique, nonmesenchymal-like
      stem cells capable of mesodermal and ectodermal neurogenic differentiation. Human
      derived skin precursors are less well characterized. In this study, the isolation
      and characterization of adherent, mesenchymal stem cell-like cells from human
      scalp tissue (hSCPs) are described. hSCPs initially isolated by both medium
      selection (ms-hSCPs) and single-cell (c-hSCPs) methods were cultured in medium
      containing epidermal growth factor and fibroblast growth factor-beta. Cultured ms
      hSCPs and c-hSCPs demonstrated a consistent growth rate, continuously replicated
      in cell culture, and displayed a stable phenotype indistinguishable from each
      other. Both hSCPs expressed surface antigen profile (CDw90, SH2, SH4, CD105,
      CD166, CD44, CD49d-e, and HLA class I) similar to that of bone marrow mesenchymal
      stem cells (BM-MSCs). The growth kinetics, surface epitopes, and differentiation
      potential of c-hSCP cells were characterized and compared with BM-MSCs. In
      addition to differentiation along the osteogenic, chondrogenic, and adipogenic
      lineages, hSCPs can effectively differentiate into neuronal precursors evident by
      neurogenic gene expression of glial fibrillary acid protein, NCAM, neuron
      filament-M, and microtubule-associated protein 2 transcripts. Therefore, hSCPs
      may potentially be a better alternative of BM-MSCs for neural repairing, in
      addition to their other mesenchymal regenerative capacity. Our study suggests
      that hSCPs may provide an alternative adult stem cell resource that may be useful
      for regenerative tissue repair and autotransplantations.

PMID- 15941859
TI  - Catalytic activities of G1 cyclin-dependent kinases and phosphorylation of
      retinoblastoma protein in mobilized peripheral blood CD34+ hematopoietic
      progenitor cells.
AB  - Depending on the source of cells, the cell cycle status of hematopoietic stem and
      progenitor cells capable of repopulating the marrow of transplant recipients is
      controversial. In this study, using biochemical methods, the cell cycle status of
      mobilized CD34+ cells was analyzed. It was demonstrated in CD34+ cell extracts
      that there was high catalytic activity of G(1) cyclin-dependent kinases 4 and 6
      (CDK4 and CDK6) but low activity of CDK2. This was in contrast to the resting
      reference cells that showed only minimal or no activity of these CDKs. Since at
      the G0-->G1-->S transition CDK4/6 and CDK2 sequentially phosphorylate the
      retinoblastoma protein (pRB), its phosphorylation status was analyzed.
      Previously, we showed that p110RB was unphosphorylated at serine (Ser)-608 in
      CD34+ cells, consistent with the ability to suppress cell growth. Here, it was
      established that this form of pRB was phosphorylated at Ser-780, Ser-795, and Ser
      807/811 in CD34+ but not in resting reference cells. This result was therefore
      consistent with the presence of high CDK4/6 activities in CD34+ cells.
      Conversely, CDK2 activity was low and the pRB residues Ser-612 and threonine
      (Thr)-821, which are exclusively phosphorylated by CDK2 in conjunction with
      either cyclin E or A, were unphosphorylated in >90% of CD34+ cells. We therefore
      show for the first time the exact position of mobilized CD34+ cells within the
      cell cycle; that is, they do not reside in G0 but in early G1 phase and did not
      cross the restriction point into late G1 phase.

PMID- 15941860
TI  - Comparison of various bone marrow fractions in the ability to participate in
      vascular remodeling after mechanical injury.
AB  - In contrast to conventional assumption, recent reports propose the possibility
      that hematopoietic stem cells (HSCs) may have broader potential to differentiate
      into various cell types. Here, we tested the pluripotency of HSCs by comparing
      vascular lesions induced by mechanical injury after bone marrow reconstitution
      with total bone marrow (TBM) cells, c-Kit+ Sca-1+ Lin- (KSL) cells, or a single
      HSC cell (Tip-SP CD34-KSL cell, CD34- c-Kit+ Sca-1+ Lin- cell with the strongest
      dye-efflux activity) harboring green fluorescent protein (GFP). The lesions
      contained a significant number of GFP-positive cells in the TBM and KSL groups,
      whereas GFP-positive cells were rarely detected in the HSC group. These results
      suggest that transdifferentiation of a highly purified HSC seems to be a rare
      event, if it occurs at all, whereas bone marrow cells including the KSL fraction
      can give rise to vascular cells that substantially contribute to repair or lesion
      formation after mechanical injury.

PMID- 15941857
TI  - Long-term survival of dopamine neurons derived from parthenogenetic primate
      embryonic stem cells (cyno-1) after transplantation.
AB  - Dopamine (DA) neurons can be derived from human and primate embryonic stem (ES)
      cells in vitro. An ES cell-based replacement therapy for patients with
      Parkinson's disease requires that in vitro-generated neurons maintain their
      phenotype in vivo. Other critical issues relate to their proliferative capacity
      and risk of tumor formation, and the capability of migration and integration in
      the adult mammalian brain. Neural induction was achieved by coculture of primate
      parthenogenetic ES cells (Cyno-1) with stromal cells, followed by sequential
      exposure to midbrain patterning and differentiation factors to favor DA
      phenotypic specification. Differentiated ES cells were treated with mitomycin C
      and transplanted into adult immunosuppressed rodents and into a primate
      (allograft) with out immunosuppression. A small percentage of DA neurons survived
      in both rodent and primate hosts for the entire term of the study (4 and 7
      months, respectively). Other neuronal and glial populations derived from Cyno-1
      ES cells showed, in vivo, phenotypic characteristics and growth and migration
      patterns similar to fetal primate transplants, and a majority of cells (>80%)
      expressed the forebrain transcription factor brain factor 1. No teratoma
      formation was observed. In this study, we demonstrate long-term survival of DA
      neurons obtained in vitro from primate ES cells. Optimization of differentiation,
      cell selection, and cell transfer is required for functional studies of ES
      derived DA neurons for future therapeutic applications.

PMID- 15941861
TI  - Stable and uniform gene suppression by site-specific integration of siRNA
      expression cassette in murine embryonic stem cells.
AB  - We developed a simple system to introduce small interfering RNA (siRNA) into
      murine embryonic stem cells (ESCs) and then showed its stable and uniform
      expression. Using hypoxanthine guanine phosphoribosyl transferase 1 (Hprt)
      deficient ESCs as a recipient, we efficiently introduced an siRNA expression
      cassette into the Hprt locus by homologous recombination, which was easily
      detected by HAT selection. Nearly all of the HAT-resistant clones exhibited a
      silenced expression of the exogenous target gene (enhanced green fluorescent
      protein [EGFP]) or the endogenous target gene (Flk1). Flow cytometry profiles
      demonstrated that there were no significant differences in level of suppression
      among individual clones and cells. The suppressing effect by siRNA was maintained
      for more than 1 month in both undifferentiated and differentiated ESCs, while its
      persistent expression did not disturb their growth or differentiation potential.
      The stable and uniform suppression capability of this system will help to screen
      genes and provide important information regarding cell differentiation in ESCs.

PMID- 15941862
TI  - Gastrin-releasing peptide receptors in normal and neoplastic human uterus:
      involvement of multiple tissue compartments.
AB  - CONTEXT: Bombesin-like neuropeptides including gastrin-releasing peptide (GRP)
      and their corresponding receptors, mediate multiple physiological actions and
      have biological significance in cancer. However, information about the function
      of these neuropeptides and the incidence, distribution, density, and subtype of
      their receptors in human uterine tissues is scarce. OBJECTIVE: The objective of
      the study was to investigate normal and neoplastic human uterine tissues for
      their bombesin receptor status. DESIGN: In vitro subtype-specific bombesin
      receptor autoradiography was used in this study. PATIENTS: The following tissue
      samples were taken immediately after surgery: myometrium (n = 41), endometrium (n
      = 29), leiomyomas (n = 26), leiomyosarcomas (n = 6), endometrial adenocarcinomas
      (n = 28), and carcinosarcoma (n = 1). RESULTS: Normal uterine tissues expressed
      GRP receptors (GRP-Rs) in the myometrium, in subsets of secretory endometrial
      glands, and in subsets of endometrial blood vessels of the late proliferative and
      the secretory phase. Most leiomyomas (20 of 26) expressed GRP-R but not the
      leiomyosarcomas. GRP-Rs were also detected in 10 of 28 adenocarcinomas, one of
      one carcinosarcoma, and in blood vessels surrounding the adenocarcinomas. No
      other bombesin receptor subtypes (neuromedin B receptors and bb3) were detected.
      CONCLUSIONS: These findings may be of physiological and pathophysiological
      significance. The expression of GRP-R in glands and vessels during specific
      phases of the cycle suggests a timely precise physiological action of GRP in
      these targets; in certain uterine neoplasms, the GRP-R overexpression may
      contribute to tumor development because GRP is a potent growth factor.
      Furthermore, these findings may be diagnostically and therapeutically relevant.
      The expression of GRP-R in leiomyomas may allow distinguishing them from receptor
      negative leiomyosarcomas; GRP-R in leiomyomas, in a subset of endometrial
      adenocarcinomas, carcinosarcomas, and in peritumoral vessels may be candidates
      for receptor targeting in vivo.

PMID- 15941863
TI  - Evidence for abnormal left ventricular structure and function in normotensive
      individuals with familial hyperaldosteronism type I.
AB  - OBJECTIVES: To explore whether aldosterone excess can induce adverse
      cardiovascular effects independently of effects on blood pressure (BP), we sought
      evidence of disturbed cardiovascular structure or function in normotensive
      individuals with primary aldosteronism. METHODS: Eight normotensive subjects with
      genetically proven familial hyperaldosteronism type I (FH-I) were compared with
      24 age- and sex-matched normotensive controls in terms of BP, biochemical
      parameters, pulse wave velocity, and echocardiographic characteristics. RESULTS:
      Subjects with FH-I demonstrated higher serum aldosterone levels and
      aldosterone/renin ratios than controls, as expected. Despite having similar 24-h
      ambulatory BPs, subjects with FH-I demonstrated evidence of concentric remodeling
      with greater septal (mean +/- sd, 9.4 +/- 1.1 vs. 7.9 +/- 0.9 mm; P < 0.001),
      posterior wall (9.2 +/- 1.7 vs. 7.7 +/- 1.0 mm; P < 0.01), and relative wall
      (0.29 +/- 0.03 vs. 0.24 +/- 0.02; P < 0.001) thicknesses, and lower mitral early
      peak velocities (0.74 +/- 0.10 vs. 0.90 +/- 0.16 m/sec; P < 0.05), ratios of
      early to late peak diastolic transmitral flow velocity (1.56 +/- 0.24 vs. 2.06 +/
      0.41; P < 0.01), and myocardial early peak velocities (8.3 +/- 1.8 vs. 10.3 +/-
      2.6 cm/sec; P < 0.05). There were no significant differences in pulse wave
      velocity or left ventricular ejection fraction, long axis strain rate, peak
      systolic strain, cyclic variation of integrated backscatter, or posterior wall
      calibrated integrated backscatter. CONCLUSIONS: Aldosterone excess is associated
      with increased left ventricular wall thicknesses and reduced diastolic function,
      even in the absence of hypertension.

PMID- 15941864
TI  - Sex differences in the genetic basis of morning serum cortisol levels: genome
      wide screen identifies two novel loci specific to women.
AB  - CONTEXT: Relatively little is known about the influence of specific genes on
      cortisol levels, particularly morning cortisol levels. OBJECTIVE: The objective
      of this study was to identify quantitative trait loci associated with morning
      serum cortisol levels. DESIGN: We carried out a genome screen for morning serum
      cortisol using linkage and association methods tailored for use in large
      pedigrees. We conducted these analyses both in the whole sample and partitioned
      by sex. SETTING: This study was conducted on nine communal Hutterite farms in
      South Dakota. PARTICIPANTS: The Hutterites are a young founder population who
      practice a communal, farming lifestyle in the western United States and in
      Canada. Hutterites (n = 504, 53% female) aged 11-89 yr from a single pedigree
      participated in this study. MAIN OUTCOME MEASURES: The main outcome measures were
      markers significantly linked or associated with variation in morning serum
      cortisol levels. RESULTS: One genome-wide significant association was identified
      in the whole sample on 11p (D11S1981, P = 0.000092). Results of sex-partitioned
      analyses indicated that this association was restricted to females (females, P =
      0.000084; males, P = 0.20). The 146-bp allele at this locus accounted for 7% of
      the variance in morning cortisol values in females, and females homozygous for
      the allele had an 89% increase in morning cortisol levels compared with female
      noncarriers. A second genome-wide significant association in females was
      identified on 14q (D14S74, P = 0.000091). CONCLUSIONS: Our results suggest that
      the genetic determinants of morning cortisol levels may be different for men and
      women and that loci on 11p and 14q influence morning cortisol levels in women.

PMID- 15941865
TI  - Long-term prognosis of thyroid nodule cases compared with nodule-free controls in
      atomic bomb survivors.
AB  - CONTEXT: Radiation exposure is associated with development of thyroid nodules.
      The long-term risk of thyroid cancer development in irradiated people with
      thyroid nodules, however, has not been clarified. OBJECTIVE: The objective of
      this study was to assess the long-term risk of cancer development in irradiated
      individuals with thyroid nodules. DESIGN, SETTING, AND PARTICIPANTS: This
      prospective study comprised 2637 atomic bomb survivors (mean age, 59 yr; 1071 men
      and 1566 women) who participated in the baseline thyroid study of the Nagasaki
      Radiation Effects Research Foundation from 1984 through 1987. The participants
      were divided into three groups at baseline by ultrasound findings: 82 cases of
      solid thyroid nodules other than cancer, 121 cases of thyroid cysts, and 2434
      thyroid nodule-free controls. Both the solid nodule and the cyst groups included
      postoperative cases. In the solid nodule group, 68 cases had ultrasound-detected
      solid nodules, including 31 cases diagnosed as benign by cytological or
      histological examination. They were followed for an average of 13.3 yr. MAIN
      OUTCOME MEASURE: Incident thyroid cancer was measured during an average 13.3-yr
      follow-up period. RESULTS: During the follow-up period, six thyroid cancer cases
      (7.3%) were found in the solid nodule group, seven cases in the controls (0.3%),
      and one case (0.8%) in the cyst group. In 31 cases with solid nodules diagnosed
      as benign, three cases (9.7%) developed thyroid cancer. The hazard ratio (HR) for
      cancer development was significantly high at 23.6 [95% confidence interval (CI),
      7.6-72.8] in the solid nodule group (HR, 40.2; 95% CI, 9.4-173.0 in 31 people
      with solid nodules diagnosed as benign) but not in the cyst group (HR, 2.7; 95%
      CI, 0.3-22.2), after controlling for age and sex. Sex, age, TSH level,
      thyroglobulin level, radiation dose, nodule volume, and increase in nodule volume
      did not predict cancer development in the solid nodule group. CONCLUSIONS: Risk
      of thyroid cancer development is high in atomic bomb survivors with solid thyroid
      nodules, suggesting the need for careful observation of irradiated individuals
      with such nodules.

PMID- 15941866
TI  - An uncommon phenotype with familial central hypogonadism caused by a novel PROP1
      gene mutant truncated in the transactivation domain.
AB  - CONTEXT: PROP1 gene mutations are usually associated with childhood onset GH and
      TSH deficiencies, whereas gonadotroph deficiency is diagnosed at pubertal age.
      OBJECTIVES: We report a novel PROP1 mutation revealed by familial normosmic
      hypogonadotropic hypogonadism. We performed in vitro transactivation and DNA
      binding experiments to study functional consequences of this mutation. SETTING:
      Three brothers were followed in the Department of Endocrinology of a French
      university hospital. PATIENTS: These patients from a consanguineous kindred were
      referred for cryptorchidism and/or delayed puberty. RESULTS: Initial
      investigations revealed hypogonadotropic hypogonadism. One of the patients had
      psychomotor retardation, intracranial hypertension, and minor renal
      malformations. The brothers reached normal adult height and developed GH and TSH
      deficiencies after age 30. A novel homozygous nonsense mutation (W194X) was found
      in the PROP1 gene, indicating that the protein is truncated in its
      transactivation domain. Transfection studies confirmed the deleterious effect of
      this mutation, whose transactivation capacity was only 34.4% of that of the wild
      type. Unexpectedly altered DNA-binding properties suggested that the C-terminal
      end of the factor plays a role in protein-DNA interaction. CONCLUSIONS: PROP1
      mutations should be considered among the growing number of genetic causes of
      initially isolated hypogonadotropic hypogonadism. This report extends the
      phenotype variability associated with PROP1 mutations.

PMID- 15941867
TI  - Excessive daytime sleepiness in a general population sample: the role of sleep
      apnea, age, obesity, diabetes, and depression.
AB  - CONTEXT: Excessive daytime sleepiness (EDS) is commonly considered a cardinal
      sign of sleep apnea; however, the mechanism underlying the association is
      unclear. OBJECTIVE: The purpose of this study was to assess the association
      between the complaint of EDS and sleep apnea, considering a wide range of
      possible risk factors in a population sample. DESIGN AND SETTING: We examined
      this question in the Penn State cohort (a random sample of 16,583 men and women
      from central Pennsylvania, ranging in age from 20 to 100 yr). A random subset of
      this cohort (n = 1,741) was further evaluated for one night in the sleep
      laboratory. MAIN OUTCOME MEASURE: The main measure was a complaint of EDS.
      RESULTS: The final logistic regression model indicated depression was the most
      significant risk factor for EDS followed by body mass index, age, typical sleep
      duration, diabetes, smoking, and finally sleep apnea. The strength of the
      association with EDS decreased with increasing age, whereas the association of
      depression with EDS was stronger in the young. EDS is more prevalent in the young
      (<30 yr), suggesting the presence of unmet sleep needs and depression, and in the
      very old (>75 yr), suggesting increasing medical illness and health problems. EDS
      was associated with a reduced report of typical sleep duration without any
      association with objective polysomnographic measures. CONCLUSIONS: It appears
      that the presence of EDS is more strongly associated with depression and
      metabolic factors than with sleep-disordered breathing or sleep disruption per
      se. Our findings suggest that patients with a complaint of EDS should be
      thoroughly assessed for depression and obesity/diabetes independent of whether
      sleep-disordered breathing is present.

PMID- 15941868
TI  - Depression in anorexia nervosa: a risk factor for osteoporosis.
AB  - CONTEXT: Both anorexia nervosa (AN) and depression are associated with
      osteoporosis. We hypothesized that adolescent girls with AN and depression will
      have lower bone mineral density (BMD) than anorexic girls without depression.
      OBJECTIVE: The objective of this study was to investigate whether depression is
      an independent risk factor for osteoporosis in anorexic adolescent girls. DESIGN:
      This study was cross-sectional. SETTING: This study was conducted at the
      University Children's Hospital (Bialystok, Poland) from October 2002 through
      September 2003. PARTICIPANTS: Forty-five Caucasian anorexic girls aged 13-23 yr,
      matched by age, Tanner stage, weight, height, calcium intake, and duration of AN,
      were studied, including 14 with comorbid depression (based on Hamilton Depression
      Rating Scale and Montgomery-Asberg Depression Rating Scale) and 31 anorexic girls
      without depression. MAIN OUTCOME MEASURES: Total body and lumbar spine (LS) BMD,
      fat mass, and lean mass assessed using dual-energy x-ray absorptiometry were
      compared between AN girls with and without depression. RESULTS: BMD was reduced
      in both groups, relative to reference data, but girls with AN and depression had
      lower BMD than those with AN alone (LS Z-scores, -2.6 +/- 0.3 vs. -1.7 +/- 0.3; P
      = 0.02) (mean +/- sem). Quantitative assessment of depression correlated
      independently with total body BMD (r = -0.4; P < 0.05) and LS BMD (r = -0.6; P <
      0.001). CONCLUSION: Anorexic girls with depression are at higher risk of
      osteoporosis than those without depression. The mechanisms responsible for
      decreased BMD in depression are not known. Independent treatment of the
      depressive disorder in AN may partly alleviate the bone fragility.

PMID- 15941869
TI  - Connective tissue growth factor expression in the human corpus luteum: paracrine
      regulation by human chorionic gonadotropin.
AB  - CONTEXT: The molecular mechanisms of luteolysis and its inhibition during
      maternal recognition of pregnancy remain unclear. OBJECTIVE: The objective of
      this study was to investigate the differential regulation of connective tissue
      growth factor (CTGF) expression in human corpora lutea using in vivo and in vitro
      models. DESIGN: Corpora lutea from different stages of the luteal phase and after
      luteal rescue with human chorionic gonadotropin (hCG) were studied. Primary
      cultures and cocultures of luteinized granulosa cells and luteal fibroblast-like
      cells were performed. SETTING: This study was performed at the research center of
      a university teaching hospital. PATIENTS: Women with regular cycles having
      hysterectomy for nonmalignant conditions and women undergoing oocyte collection
      for assisted conception were studied. INTERVENTIONS: CTGF localization was
      determined by in situ hybridization, and expression by quantitative RT-PCR.
      OUTCOMES: The outcome measures were the effect of hCG on the expression and
      localization of CTGF mRNA in human corpora lutea and the effect of hCG on CTGF
      expression in primary cultures of luteinized granulosa cells and luteal
      fibroblast-like cells. RESULTS: Luteal rescue reduced CTGF expression compared
      with that in the late luteal phase (P < 0.05). CTGF expression was localized to
      fibroblast-like cells and endothelial cells of larger blood vessels, not to
      steroidogenic cells. The expression of CTGF by fibroblast-like cells in vitro was
      not regulated by hCG. When cocultured with luteinized granulosa cells, fibroblast
      like cell CTGF expression was inhibited by hCG (P < 0.001). This effect was
      independent of stimulated progesterone concentrations and was not blocked by
      follistatin or indomethacin. Both IL-1alpha (P < 0.05) and cAMP (P < 0.001)
      inhibited CTGF expression in fibroblast-like cells. CONCLUSIONS: These results
      provide evidence for negative regulation of CTGF by hCG during luteal rescue
      mediated by paracrine signals.

PMID- 15941870
TI  - A novel therapeutic strategy for medullary thyroid cancer based on radioiodine
      therapy following tissue-specific sodium iodide symporter gene expression.
AB  - CONTEXT: In contrast to papillary and follicular thyroid cancer, medullary
      thyroid cancer (MTC) remains difficult to treat due to its unresponsiveness to
      radioiodine therapy and its limited responsiveness to chemo- and radiotherapy.
      OBJECTIVE: To investigate an alternative therapeutic approach, we examined the
      feasibility of radioiodine therapy of MTC after human sodium iodide symporter
      (hNIS) gene transfer using the calcitonin promoter to target hNIS gene expression
      to MTC cells (TT). DESIGN: TT cells were stably transfected with an expression
      vector, in which hNIS cDNA was coupled to the calcitonin promoter. Functional
      hNIS expression was confirmed by iodide accumulation assays, Northern and Western
      blot analysis, immunostaining, and in vitro clonogenic assay. RESULTS: hNIS
      transfected TT cells showed perchlorate-sensitive iodide uptake, accumulating 125
      I about 12-fold in vitro with organification of 4% of accumulated iodide
      resulting in a significant decrease in iodide efflux. NIS protein expression was
      confirmed by Western blot analysis using a monoclonal hNIS-specific antibody,
      which revealed a major band of a molecular mass of 80-90 kDa. In addition,
      immunostaining of hNIS-transfected TT cells revealed hNIS-specific
      immunoreactivity, which was primarily membrane associated. In an in vitro
      clonogenic assay, 84% of NIS-transfected TT cells were killed by exposure to 131
      I, whereas only about 0.6% of control cells were killed. CONCLUSIONS: A
      therapeutic effect of 131-I has been demonstrated in MTC cells after induction of
      tissue-specific iodide uptake activity by calcitonin promoter-directed hNIS
      expression. This study demonstrates the potential of NIS as a therapeutic gene,
      allowing radioiodine therapy of MTC after tissue-specific NIS gene transfer.

PMID- 15941871
TI  - Detection of adrenocorticotropin-secreting pituitary adenomas by magnetic
      resonance imaging in children and adolescents with cushing disease.
AB  - CONTEXT: We recently showed that pre- and postcontrast spoiled gradient-recalled
      acquisition in the steady-state (SPGR) was superior to conventional pre- and
      postcontrast T-1 weighted spin echo (SE) acquisition magnetic resonance imaging
      (MRI) for the diagnostic evaluation of pituitary tumors in adult patients.
      OBJECTIVE: The present investigation assessed the use of SPGR vs. SE-MRI in the
      diagnostic evaluation of ACTH-secreting tumors in children and adolescents with
      Cushing disease. DESIGN: Data were analyzed retrospectively from a series of
      patients seen over 7 yr (1997-2004). SETTING: The setting for this study was a
      tertiary care referral center. PATIENTS: Thirty children with Cushing disease (13
      females and 17 males with a mean age of 12 +/- 3 yr) were studied. INTERVENTIONS
      AND OUTCOME MEASURES: Imaging results were compared with surgical and
      pathological findings and the clinical outcome. RESULTS: Twenty-eight patients
      had microadenomas, and two had macroadenomas; the latter were identified by both
      MRI techniques. Precontrast SE and SPGR-MRI identified four and six of the
      microadenomas, respectively. Postcontrast SPGR-MRI identified the location of the
      tumor in 18 of 28 patients, whereas postcontrast SE-MRI identified the location
      and accurately estimated the size of the tumor in only five patients (P < 0.001).
      CONCLUSIONS: We conclude that conventional MRI, even with contrast enhancement,
      mostly failed to identify ACTH-secreting microadenomas in children and
      adolescents with Cushing disease. Postcontrast SPGR-MRI was superior to SE-MRI
      and should be used in addition to conventional SE-MRI in the pituitary evaluation
      of children and adolescents with suspected Cushing disease.

PMID- 15941872
TI  - Obesity treatment: does one size fit all?

PMID- 15941873
TI  - Dietary fat and genotype: toward individualized prescriptions for lifestyle
      changes.

PMID- 15941874
TI  - The phenomenon of altered risk factor patterns or reverse epidemiology in persons
      with advanced chronic kidney failure.
AB  - This lecture reviews a recently described phenomenon in patients with advanced
      chronic renal failure who are undergoing maintenance hemodialysis or chronic
      peritoneal dialysis. The phenomenon is called risk factor reversal, reverse
      epidemiology, or altered risk factor patterns, and it has to do with altered
      relations between risk factors and the hazard ratio for morbidity or mortality in
      these persons. This risk factor reversal phenomenon has been reported for body
      weight-for-height measures, systolic and diastolic blood pressures, and serum
      total cholesterol, LDL-cholesterol, homocysteine, creatinine, and parathyroid
      hormone concentrations, as well as metabolic acidemia. These risk factors are
      often associated with cardiovascular morbidity or mortality and with total
      mortality. The relations between these risk factors and the hazard ratio for
      morbidity or mortality vary from major alterations from the relations found in
      the general population (eg, for systolic or diastolic hypertension versus the
      hazard ratio of mortality) to a complete, mirror-image reversal (eg, that for
      body mass index versus the hazard ratio of mortality). Several potential causes
      of altered risk factor patterns are discussed here, and it is suggested that the
      major cause is the confounding effects of protein-energy malnutrition and
      inflammatory disorders, which commonly occur in maintenance dialysis patients.

PMID- 15941875
TI  - Risk of overweight and obesity among semivegetarian, lactovegetarian, and vegan
      women.
AB  - BACKGROUND: Observational studies suggest that a plant-based diet is inversely
      related to body mass index (BMI), overweight, and obesity. OBJECTIVE: Our
      objective was to examine the BMI (kg/m(2)) and risk of overweight and obesity of
      self-defined semivegetarian, lactovegetarian, and vegan women. DESIGN: Data
      analyzed in this cross-sectional study were from 55459 healthy women
      participating in the Swedish Mammography Cohort. Women were asked whether they
      considered themselves to be omnivores (n = 54257), semivegetarians (n = 960),
      lactovegetarians (n = 159), or vegans (n = 83), and this question was the main
      exposure variable in this study. In secondary analyses, we reclassified women as
      lactovegetarians on the basis of food intakes reported on the food-frequency
      questionnaire. RESULTS: The prevalence of overweight or obesity (BMI >/= 25) was
      40% among omnivores, 29% among both semivegetarians and vegans, and 25% among
      lactovegetarians. In multivariate, adjusted logistic regression analyses, self
      identified vegans had a significantly lower risk of overweight or obesity [odds
      ratio (OR) = 0.35; 95% CI: 0.18, 0.69] than did omnivores, as did
      lactovegetarians (OR = 0.54; 95% CI: 0.35, 0.85) and semivegetarians (OR = 0.52;
      95% CI: 0.43, 0.62). Risk of overweight or obesity remained significantly lower
      among lactovegetarians classified on the basis of the food-frequency
      questionnaire (OR = 0.48; 95% CI: 0.30, 0.78). CONCLUSIONS: Even if vegetarians
      consume some animal products, our results suggest that self-identified
      semivegetarian, lactovegetarian, and vegan women have a lower risk of overweight
      and obesity than do omnivorous women. The advice to consume more plant foods and
      less animal products may help individuals control their weight.

PMID- 15941876
TI  - Changes in adipose tissue gene expression with energy-restricted diets in obese
      women.
AB  - BACKGROUND: The effect of energy restriction and macronutrient composition on
      gene expression in adipose tissue is not well defined. OBJECTIVE: The aim of the
      study was to investigate the effect of different low-energy diets on gene
      expression in human adipose tissue. DESIGN: Forty obese women were randomly
      assigned to a moderate-fat, moderate-carbohydrate diet or a low-fat, high
      carbohydrate hypoenergetic (-600 kcal/d) diet for 10 wk. Subcutaneous adipose
      tissue samples were obtained before and after the diet period. High-quality RNA
      samples were obtained from 23 women at both time points, and these samples were
      hybridized to microarrays containing the 8500 most extensively described human
      genes. The results were confirmed by separate messenger RNA measurements.
      RESULTS: Both diets resulted in weight losses of approximately 7.5% of baseline
      body weight. A total of 52 genes were significantly up-regulated and 44 were down
      regulated as a result of the intervention, and no diet-specific effect was
      observed. No major effect on lipid-specific transcription factors or genes
      regulating signal transduction, lipolysis, or synthesis of acylglycerols was
      observed. Most changes were modest (<25% of baseline), but all genes regulating
      the formation of polyunsaturated fatty acids from acetyl-CoA and malonyl-CoA were
      markedly down-regulated (35-60% decrease). CONCLUSIONS: Macronutrients have a
      secondary role in changes in adipocyte gene expression after energy-restricted
      diets. The most striking alteration after energy restriction is a coordinated
      reduction in the expression of genes regulating the production of polyunsaturated
      fatty acids.

PMID- 15941877
TI  - Body fat redistribution after weight gain in women with anorexia nervosa.
AB  - BACKGROUND: Body image distortions are a core feature of anorexia nervosa (AN).
      Increasing evidence suggests that the fat distribution immediately after weight
      restoration in patients with AN differs from the distribution typical of healthy
      adult women. OBJECTIVE: The purpose of this study was to assess body fat
      distribution before and shortly after normalization of weight in women with AN.
      DESIGN: Body composition and fat distribution were assessed by anthropometry,
      dual-energy X-ray absorptiometry, and whole-body magnetic resonance imaging in 29
      women with AN before and after weight normalization and at a single time point in
      15 female control subjects. Hormone concentrations were also evaluated in
      patients and control subjects. RESULTS: During approximately 10.1 +/- 2.9 wk
      (range: 4-17.3 wk) of treatment, patients with AN gained 12.2 +/- 3.6 kg, and
      refed weight (54.1 +/- 4.2 kg) did not differ significantly from that of control
      subjects (54.7 +/- 4.4 kg). Waist-to-hip circumference ratio (P < 0.006), total
      trunk fat (P < 0.003), visceral adipose tissue (P < 0.006), and intramuscular
      adipose tissue (P < 0.003) were significantly greater in the weight-recovered
      patients than in the control subjects. In contrast, after refeeding, total
      subcutaneous adipose tissue and skeletal muscle mass did not differ significantly
      between the patients and control subjects. In patients with AN, serum cortisol
      decreased and serum estradiol increased significantly with refeeding but not to
      control concentrations. CONCLUSIONS: In women with AN, normalization of weight in
      the short term is associated with an abnormal distribution of body fat. The
      implications of these findings for the long-term psychological and physical
      health of women with AN are unknown.

PMID- 15941878
TI  - Predictors of weight loss and reversal of comorbidities in malabsorptive
      bariatric surgery.
AB  - BACKGROUND: Cardiovascular and metabolic comorbidities are dramatically increased
      in severe obesity, a condition highly resistant to nonsurgical therapy.
      OBJECTIVE: The objective was to identify predictors of weight loss and reversal
      of comorbidity in obese patients undergoing malabsorptive bariatric surgery.
      DESIGN: Morbidly obese men and women (n = 107) were studied before and 2 y after
      biliopancreatic diversion (BPD). Body composition, serum lipid profile, oral
      glucose tolerance, and blood pressure were measured. Insulin sensitivity was
      determined by use of a euglycemic clamp. The length of the small intestine was
      measured during surgery. RESULTS: Intestinal length was 671 +/- 99 cm, and the
      residual absorbing intestine after BPD ranged from 54% to 24% of initial length.
      Patients lost an average of 36% of their initial weight, with approximately 50%
      of them reaching a body mass index (in kg/m(2)) < 30. Serum cholesterol decreased
      (from 4.58 +/- 1.11 to 3.34 +/- 0.73 mmol/L; P < 0.0001), as did serum
      triacylglycerols (from 1.52 +/- 0.59 to 0.88 +/- 0.35 mmol/L; P < 0.0001),
      whereas insulin sensitivity rose 150% (from 26 +/- 4 to 64 +/- 11 micromol . min(
      1) . kg fat-free mass(-1); P < 0.0001). Diabetes (in 23% of patients before
      surgery) and hypertension (in 83%) were reduced (by 88% and 96%, respectively)
      after surgery. In a multivariate model (including sex, age, intestinal length,
      presence of diabetes, insulin sensitivity, and initial fat mass), age and
      diabetes were independent, negative predictors of weight loss, whereas initial
      fat mass was a strong positive predictor (r(2) = 0.51). CONCLUSIONS: Two years
      after BPD in morbidly obese patients, comorbidities are largely corrected and
      insulin resistance is fully reversed despite persistent obesity. Initial fat
      mass, but not residual intestinal length, is the strongest predictor of weight
      loss after BPD.

PMID- 15941879
TI  - Effect of an energy-restricted, high-protein, low-fat diet relative to a
      conventional high-carbohydrate, low-fat diet on weight loss, body composition,
      nutritional status, and markers of cardiovascular health in obese women.
AB  - BACKGROUND: Limited evidence suggests that a higher ratio of protein to
      carbohydrate during weight loss has metabolic advantages. OBJECTIVE: The
      objective was to evaluate the effects of a diet with a high ratio of protein to
      carbohydrate during weight loss on body composition, cardiovascular disease risk,
      nutritional status, and markers of bone turnover and renal function in overweight
      women. DESIGN: The subjects were randomly assigned to 1 of 2 isocaloric 5600-kJ
      dietary interventions for 12 wk according to a parallel design: a high-protein
      (HP) or a high-carbohydrate (HC) diet. RESULTS: One hundred women with a mean (+/
      SD) body mass index (in kg/m(2)) of 32 +/- 6 and age of 49 +/- 9 y completed the
      study. Weight loss was 7.3 +/- 0.3 kg with both diets. Subjects with high serum
      triacylglycerol (>1.5 mmol/L) lost more fat mass with the HP than with the HC
      diet (x +/- SEM: 6.4 +/- 0.7 and 3.4 +/- 0.7 kg, respectively; P = 0.035) and had
      a greater decrease in triacylglycerol concentrations with the HP (-0.59 +/- 0.19
      mmol/L) than with the HC (-0.03 +/- 0.04 mmol/L) diet (P = 0.023 for diet x
      triacylglycerol interaction). Triacylglycerol concentrations decreased more with
      the HP (0.30 +/- 0.10 mmol/L) than with the HC (0.10 +/- 0.06 mmol/L) diet (P =
      0.007). Fasting LDL-cholesterol, HDL-cholesterol, glucose, insulin, free fatty
      acid, and C-reactive protein concentrations decreased with weight loss. Serum
      vitamin B-12 increased 9% with the HP diet and decreased 13% with the HC diet (P
      < 0.0001 between diets). Folate and vitamin B-6 increased with both diets;
      homocysteine did not change significantly. Bone turnover markers increased 8-12%
      and calcium excretion decreased by 0.8 mmol/d (P < 0.01). Creatinine clearance
      decreased from 82 +/- 3.3 to 75 +/- 3.0 mL/min (P = 0.002). CONCLUSION: An energy
      restricted, high-protein, low-fat diet provides nutritional and metabolic
      benefits that are equal to and sometimes greater than those observed with a high
      carbohydrate diet.

PMID- 15941880
TI  - Chronic coffee consumption has a detrimental effect on aortic stiffness and wave
      reflections.
AB  - BACKGROUND: The effect of coffee consumption on the cardiovascular system is
      still an unresolved issue. Aortic stiffness and wave reflections are important
      prognosticators of cardiovascular disease risk. We have shown that caffeine
      acutely increases aortic stiffness and wave reflections. OBJECTIVE: The objective
      was to investigate the effect of chronic coffee consumption on aortic stiffness
      and wave reflections. DESIGN: This was a cross-sectional study of 228 healthy
      subjects: 141 men (x +/- SD: 41 +/- 8 y old) and 87 women (41 +/- 9 y old).
      Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV).
      Wave reflections were evaluated with augmentation index (AIx) and augmented
      pressure (AP) of the aortic pressure waveform with the use of high-fidelity pulse
      wave analysis. Coffee consumption was ascertained over 1 y with a food-frequency
      questionnaire. RESULTS: A linear relation between coffee consumption and PWV,
      AIx, and AP was observed (P for trend < 0.05). Compared with the nonconsumption
      group, PWV was on average 13% higher, AIx was 2-fold higher, and AP was 2.4-fold
      higher (P < 0.01 for all) in the high-consumption group (>450 mL/d). The findings
      remained significant after control for confounders such as age, sex, smoking
      habits, body mass index, total and LDL cholesterol, triacylglycerols, blood
      glucose, mean blood pressure, and heart rate. The linear relation (P for trend <
      0.05) observed between coffee consumption and arterial pressures was largely
      explained when the covariates were entered in the model. CONCLUSIONS: Chronic
      coffee consumption exerts a detrimental effect on aortic stiffness and wave
      reflections, which may increase the risk of cardiovascular disease.

PMID- 15941881
TI  - Measures of adiposity in the identification of metabolic abnormalities in elderly
      men.
AB  - BACKGROUND: Body mass index (BMI; in kg/m(2)) is considered a poor indicator of
      overall and abdominal obesity in the elderly. OBJECTIVES: Our goal was to
      determine which simple anthropometric measurements [BMI, waist-to-hip ratio
      (WHR), waist circumference (WC), percentage body fat (%BF), or fat mass (FM)] are
      most closely associated with metabolic risk factors and insulin resistance in
      elderly men. DESIGN: This was a cross-sectional study of 2924 men aged 60-79 y
      with no history of coronary heart disease, stroke, or diabetes who were drawn
      from general practices in 24 British towns. RESULTS: BMI and WC were the measures
      most strongly associated with the metabolic syndrome (>/=3 of the following:
      hypertension, low HDL cholesterol, high triacylglycerols, or high blood glucose)
      and insulin resistance. For a 1-SD increase in BMI, WC, WHR, %BF, and FM, the
      odds ratios (95% CIs) of having the metabolic syndrome after adjustment for age,
      socioeconomic status, smoking status, and physical activity were as follows: BMI,
      1.61 (1.44, 1.79); WC, 1.65 (1.48, 1.81); WHR, 1.49 (1.34, 1.66); %BF, 1.41
      (1.25, 1.59); and FM, 1.53 (1.38, 1.70). For insulin resistance, the odds ratios
      (95% CIs) were as follows: 2.48 (2.22, 2.77), 2.46 (2.19, 2.65), 1.75 (1.59,
      1.93), 1.79 (1.60, 2.00), and 2.10 (1.88, 2.34), respectively. In normal-weight
      (BMI < 25) and overweight (BMI 25-29.9) men, the presence of the metabolic
      syndrome and insulin resistance increased with increasing WC; this did not occur
      in obese men. CONCLUSIONS: BMI and WC are the simple measures of adiposity most
      strongly associated with metabolic abnormalities in elderly men. Our findings
      suggest that WC can be used as a complementary measurement to identify health
      risks in normal-weight and overweight elderly persons.

PMID- 15941882
TI  - Relation of diet to cardiovascular disease risk factors in subjects with
      cardiovascular disease in Australia and New Zealand: analysis of the Long-Term
      Intervention with Pravastatin in Ischaemic Disease trial.
AB  - BACKGROUND: Comparisons of the relation of diet with coronary heart disease (CHD)
      between countries with similar socioeconomic environments have been few. Patients
      in Australia and New Zealand (n = 9014) who participated in a large secondary
      prevention trial had significantly different CHD mortality rates. OBJECTIVE: The
      objective of this study was to ascertain the effects of nutrient consumption on
      cardiovascular disease risk in patients from the 2 countries. DESIGN: Nutrient
      consumption patterns were surveyed in a subgroup of 1077 patients on 3 occasions
      over 4 y during an intervention trial with a statin. RESULTS: Within the entire
      cohort of 9014 patients, the New Zealanders had significantly (40%) more
      cardiovascular deaths than did the Australians. In the subgroup of 1077 patients,
      the New Zealanders were found at entry to have eaten significantly more total
      (69.34 +/- 12.35 compared with 66.45 +/- 12.9 g/d) and saturated (26.23 +/- 8.41
      compared with 24.37 +/- 7.36 g/d) fat (P < 0.001 for each) and to have
      significantly (4%) higher concentrations of LDL cholesterol (3.96 +/- 0.74
      compared with 3.8 +/- 0.76 mmol/L; P < 0.001) than did the Australians. At
      baseline, patients with previous coronary artery bypass grafting had diets that
      were significantly different from those of patients without previous coronary
      artery bypass grafting. Relations between nutrients and plasma lipids confirmed
      the direct effects of saturated fatty acids on LDL cholesterol and of alcohol on
      plasma triacylglycerol and HDL cholesterol. Dietary counseling throughout the
      trial led to significant improvements in compliance with guidelines. However,
      neither the baseline nor the improved 1-y nutrient intakes predicted future
      changes in cardiovascular events. CONCLUSION: Differences in CHD mortality and in
      LDL-cholesterol concentrations between 2 populations with similar socioeconomic
      and cultural backgrounds were consistent with the amounts and types of fats
      eaten.

PMID- 15941883
TI  - Waist circumference and abdominal adipose tissue distribution: influence of age
      and sex.
AB  - BACKGROUND: The influence of age and sex on the distribution of abdominal adipose
      tissue for a given waist circumference (WC) is unclear. OBJECTIVE: The objective
      was to investigate the influence of age and sex on total (TAAT), visceral (VAT),
      and abdominal subcutaneous (ASAT) adipose tissue for a given WC. DESIGN: Body
      composition was assessed by whole-body magnetic resonance imaging in 147 younger
      men (< 50 y), 83 older men, 171 younger (premenopausal) women, and 80 older
      (postmenopausal) women with a wide range (16-40; in kg/m(2)) of body mass
      indexes. RESULTS: Within each sex, the regression lines between WC and TAAT were
      not significantly different (P > 0.1) between younger and older groups. Collapsed
      across age groups, women had more TAAT for a given WC than did men; however, this
      difference was significantly reduced with increasing WC (P < 0.05). Within each
      sex, regression lines derived for WC and ASAT were not significantly different
      between younger and older groups (P > 0.1). Collapsed across age groups, women
      had 1.8 kg more ASAT for a given WC (P < 0.05) than did men across the range of
      WCs. Within each sex, older men and women had a significantly greater increase in
      VAT for a given WC (P < 0.05) than did younger men and women. Furthermore,
      independent of age group, the slopes for WC and VAT were significantly higher (P
      < 0.05) in men than in women. CONCLUSIONS: There are significant sex differences
      in TAAT, VAT, and ASAT for a given WC. Furthermore, the relation between WC and
      VAT is substantially influenced by age.

PMID- 15941884
TI  - Energy balance in early-stage Huntington disease.
AB  - BACKGROUND: Huntington disease (HD) is a genetic neurologic disorder. Weight loss
      is common in HD and is related to progression of the disease, but the cause of
      weight loss remains unclear. OBJECTIVE: The study objective was to compare 24-h
      energy expenditure (EE) and energy intake in persons with early midstage HD with
      those of matched control subjects to determine how HD affects energy balance.
      DESIGN: EE was assessed in 13 subjects with early-stage HD and in 9 control
      subjects via indirect calorimetry in a human respiratory chamber. Energy intake
      was determined by weighing all food provided and all leftovers from an ad libitum
      diet. Body composition was measured via air-displacement plethysmography. Stage
      of disease was estimated on the basis of the Unified Huntington's Disease Rating
      Scale and modified Mini-Mental Status examinations. Regression analysis included
      all 13 HD subjects; t tests were used for the comparisons between matched HD and
      control subjects. RESULTS: 24-h EE was 11% higher in the HD subjects than in the
      control subjects (NS). This difference was due to a higher (P = 0.043) waking
      metabolic rate, which was related to a significantly greater displacement of the
      center of mass by HD subjects than by control subjects (P = 0.028). On average,
      both groups were in positive energy balance and exceeded their energy expenditure
      by 2510-2929 kJ. CONCLUSIONS: Higher 24-h EE in persons with early midstage HD is
      due to increased physical activity, both voluntary and involuntary. However, HD
      subjects are able to maintain positive energy balance when offered adequate
      amounts of food in a controlled setting.

PMID- 15941885
TI  - Water balance, hydration status, and fat-free mass hydration in younger and older
      adults.
AB  - BACKGROUND: Older adults are at increased risk of dehydration, yet water balance
      is understudied in this population. OBJECTIVE: This controlled diet study
      assessed the effect of age on water input, output, and balance in healthy adults.
      Hydration status (plasma osmolality and urine specific gravity) and body
      composition were also measured. DESIGN: Eleven men and 14 women aged 23-46 y and
      10 men and 11 women aged 63-81 y were subjects. Water balance was assessed during
      days 7-10 of three 18-d controlled feeding trials with protein intakes of 0.50,
      0.75, and 1.00 g . kg(-1) . d(-1). Total water input included water from the
      provided foods and beverages, ad libitum intake, and metabolic production. Water
      output included the losses in urine and stool and the insensible losses from
      respiration and nonsweating perspiration. RESULTS: Ad libitum water consumption,
      total water intake, water output through urine, total water output, and net water
      balance were not different in the older subjects than in the younger subjects.
      Markers of hydration status were within the range of clinical normalcy for all
      groups. Total body water (TBW) was not significantly different, fat-free mass
      (FFM) was significantly lower (P < 0.05), and FFM hydration (TBW:FFM) was
      significantly higher (P < 0.05) in the older subjects than in the younger
      subjects. Dietary protein intake did not influence any of these results.
      CONCLUSIONS: These results show that healthy older adults maintain water input,
      output, and balance comparable to those of younger adults and have no apparent
      changes in hydration status. The results support that the hydration of FFM is
      increased in older men and women.

PMID- 15941886
TI  - Plant sterols are efficacious in lowering plasma LDL and non-HDL cholesterol in
      hypercholesterolemic type 2 diabetic and nondiabetic persons.
AB  - BACKGROUND: Because of hyperglycemia and hyperinsulinemia, diabetic persons have
      higher cholesterol synthesis and lower cholesterol absorption rates than do
      nondiabetic persons. Differences in plant sterol efficacy between diabetic and
      nondiabetic persons have not been examined. OBJECTIVE: The objective was to
      compare the degree of response of plasma lipid concentrations and glycemic
      control to plant sterol consumption in a controlled diet between
      hypercholesterolemic type 2 diabetic and nondiabetic subjects. DESIGN: Fifteen
      nondiabetic subjects and 14 diabetic subjects participated in a double-blinded,
      randomized, crossover, placebo-controlled feeding trial. The diet included 1.8
      g/d of either plant sterols or cornstarch placebo over 21 d, separated by a 28-d
      washout period. RESULTS: Plant sterol consumption significantly reduced (P <
      0.05) LDL-cholesterol concentrations from baseline in both nondiabetic and
      diabetic subjects by 15.1% and 26.8%, respectively. The diabetic subjects had
      significantly (P < 0.05) lower absolute concentrations of total cholesterol after
      treatment than did the nondiabetic subjects; however, there was no significant
      difference in the percentage change from the beginning to the end of the trial.
      There was also a significant decrease (P < 0.05) in absolute non-HDL-cholesterol
      concentrations after treatment in both groups. CONCLUSIONS: The results showed
      that plant sterols are efficacious in lowering LDL cholesterol and non-HDL
      cholesterol in both diabetic and nondiabetic persons. Plant sterol consumption
      may exist as a dietary management strategy for hypercholesterolemia in persons
      with type 2 diabetes.

PMID- 15941887
TI  - Dietary peptides increase endogenous amino acid losses from the gut in adults.
AB  - BACKGROUND: Accurate estimates of endogenous ileal total nitrogen and amino acid
      flows are necessary to ascertain true dietary amino acid digestibility
      coefficients and for the factorial estimation of dietary amino acid requirements.
      OBJECTIVE: The objective was to ascertain endogenous amino acid losses from the
      small bowel in human subjects consuming a protein-free diet or a diet with enzyme
      hydrolyzed casein (EHC; MW <5000) as the sole source of nitrogen. DESIGN: The
      subjects were 8 men and women with terminal ileum ileostomies after ulcerative
      colitis who consumed the protein-free and EHC-based diets in a crossover design.
      Each subject received each test diet in single meals followed by 2 consecutive 9
      h total collections of digesta. Digesta samples for the EHC treatment were
      centrifuged and ultrafiltered (10 000 MW cutoff), with the precipitate-plus
      retentate fraction (>10 000 MW) providing a measurement of endogenous ileal amino
      acids. RESULTS: The mean endogenous flows for most of the amino acids and
      nitrogen were significantly (P < 0.05) higher when determined with the EHC-based
      diet than with the protein-free diet. Mean (n = 8) endogenous ileal nitrogen
      flows were 2061 and 4233 mug/g dry matter intake for the protein-free and EHC
      based diets, respectively. CONCLUSION: The traditional protein-free method
      underestimates endogenous ileal amino acid loss in adults.

PMID- 15941888
TI  - Ferritin concentrations in dried serum spots prepared by standard compared with
      simplified approaches: a validation study in Guatemala City.
AB  - BACKGROUND: Spot ferritin assay on dried serum spot (DSS) samples provides
      reliable and accurate assessment. Standard DSS preparations, however, involve
      precise serum aliquots and require some skill and training of field personnel.
      OBJECTIVE: We evaluated the validity of the spot ferritin assay on DSS samples
      prepared by simplified approaches and standard technique in Guatemala City.
      DESIGN: Venous blood (5 mL) was obtained from 104 subjects aged 24 +/- 15 y (x +/
      SD) and transferred into nonheparin-containing (2 plain and 2 self-sealing)
      capillary blood collection tubes. Three DSS samples were prepared: A (standard,
      20 microL serum), B (blot, approximately 30-35 mm serum column), and C
      (dispenser, 20 microL serum pushed directly from self-sealing capillary tubes
      with a dispenser). Spots were air-dried and placed in hermetic plastic bags with
      a desiccant. Two weeks later, entire spots for DSS A and C samples and a circle
      in the center for DSS B samples were analyzed. RESULTS: DSS ferritin A, B, and C
      correlated strongly with traditional ferritin (r = 0.71-0.88, P < 0.001). The
      geometric mean (-1 SD and +1 SD) values for the DSS A, B, and C and traditional
      ferritin methods were 27.5 (12.6, 60.2), 32.4 (13.5, 77.6), 27.5 (11.7, 64.6),
      and 30.2 (13.8, 66.1) microg/L, respectively, and did not differ significantly.
      The difference in ferritin values by various DSS approaches compared with the
      traditional approach was small (<4 microg/L; P > 0.05). CONCLUSIONS: Simplified
      and standard DSS methods provide accurate iron-status assessment in population
      studies. The simplified DSS approaches for serum ferritin measurement need to be
      evaluated further in populations in whom iron deficiency is prevalent.

PMID- 15941889
TI  - Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh.
AB  - BACKGROUND: Indian Asian men residing in the United Kingdom have a higher
      prevalence of hyperhomocysteinemia than do their European counterparts. This has
      been largely attributed to dietary deficiencies in cobalamin associated with
      vegetarianism among these Indian Asians. OBJECTIVE: We aimed to ascertain the
      prevalence of folate and cobalamin deficiencies and hyperhomocysteinemia in
      Bangladesh. DESIGN: Plasma concentrations of homocysteine, folate, and cobalamin
      and urinary concentrations of creatinine were assessed in 1650 adults in
      Bangladesh. RESULTS: The prevalence of hyperhomocysteinemia (men: >11.4
      micromol/L; women: >10.4 micromol/L) was markedly (P < 0.0001) greater among men
      (63%; x +/- SD: 15.3 +/- 9.5 micromol/L) than among women (26%; 9.5 +/- 4.7
      micromol/L). Folate was lower (9.8 +/- 6.5 and 12.3 +/- 7.6 nmol/L,
      respectively), whereas cobalamin was higher (281 +/- 115 and 256 +/- 118 pmol/L,
      respectively) (P < 0.0001 for both) among men than among women. Folate explained
      15% and cobalamin explained 5% of the variation in homocysteine concentrations.
      For men, folate (P = 0.005) and cobalamin (P = 0.03) were positively correlated
      with urinary creatinine. Smoking (P < 0.0003) and betelnut use (P < 0.0002) were
      independent negative predictors of folate. CONCLUSIONS: Bangladeshi men have a
      high prevalence of hyperhomocysteinemia, which is more closely associated with
      folate than with cobalamin, although other factors, eg, smoking and betelnut use,
      may also contribute to its cause. The positive correlations between urinary
      creatinine and plasma folate and cobalamin were unanticipated and could suggest
      that, in marginal nutrition, these vitamins may be limiting for creatine
      biosynthesis.

PMID- 15941890
TI  - Betaine concentration as a determinant of fasting total homocysteine
      concentrations and the effect of folic acid supplementation on betaine
      concentrations.
AB  - BACKGROUND: Remethylation of homocysteine to methionine can occur through either
      the folate-dependent methionine synthase pathway or the betaine-dependent betaine
      homocysteine methyltransferase pathway. The relevance of betaine as a determinant
      of fasting total homocysteine (tHcy) is not known, nor is it known how the 2
      remethylation pathways are interrelated. OBJECTIVE: The objectives of the study
      were to examine the relation between plasma betaine concentration and fasting
      plasma tHcy concentrations and to assess the effect of folic acid supplementation
      on betaine concentrations in healthy subjects. DESIGN: A double-blind randomized
      trial of 6 incremental daily doses of folic acid (50-800 microg/d) or placebo was
      carried out in 308 Dutch men and postmenopausal women (aged 50-75 y). Fasted
      blood concentrations of tHcy, betaine, choline, dimethylglycine, and folate were
      measured at baseline and after 12 wk of vitamin supplementation. RESULTS:
      Concentrations of tHcy were inversely related to the betaine concentration (r = 
      0.17, P < 0.01), and the association was independent of age, sex, and serum
      concentrations of folate, creatinine, and cobalamin. Folic acid supplementation
      increased betaine concentration in a dose-dependent manner (P for trend = 0.018);
      the maximum increase (15%) was obtained at daily doses of 400-800 microg/d.
      CONCLUSIONS: The plasma betaine concentration is a significant determinant of
      fasting tHcy concentrations in healthy humans. Folic acid supplementation
      increases the betaine concentration, which indicates that the 2 remethylation
      pathways are interrelated.

PMID- 15941891
TI  - Plasma choline and betaine and their relation to plasma homocysteine in normal
      pregnancy.
AB  - BACKGROUND: Plasma concentrations of total homocysteine (tHcy) decrease during
      pregnancy. This reduction has been investigated in relation to folate status, but
      no study has addressed the possible role of betaine and its precursor choline.
      OBJECTIVE: We investigated the courses of plasma choline and betaine during
      normal human pregnancy and their relations to plasma tHcy. DESIGN: Blood samples
      were obtained monthly; the initial samples were taken at gestational week (GW) 9,
      and the last samples were taken approximately 3 mo postpartum. The study
      population comprised 50 women of West African descent. Most of the subjects took
      folic acid irregularly. RESULTS: Plasma choline (geometric x; 95% reference
      interval) increased continuously during pregnancy, from 6.6 (4.5, 9.7) micromol/L
      at GW 9 to 10.8 (7.4, 15.6) micromol/L at GW 36. Plasma betaine decreased in the
      first half of pregnancy, from 16.3 (8.6, 30.8) micromol/L at GW 9 to 10.3 (6.6,
      16.2) micromol/L at GW 20 and remained constant thereafter. We confirmed a
      reduction in plasma tHcy, and the lowest concentration was found in the second
      trimester. From GW 16 onward, an inverse relation between plasma tHcy and betaine
      was observed. Multiple regression analysis showed that plasma betaine was a
      strong predictor of plasma tHcy from GW 20 onward. CONCLUSIONS: The steady
      increase in choline throughout gestation may ensure choline availability for
      placental transfer with subsequent use by the growing fetus. Betaine becomes a
      strong predictor of tHcy during the course of pregnancy. Both of these findings
      emphasize the importance of choline and betaine status during normal human
      pregnancy.

PMID- 15941892
TI  - Oxidative stress, diet, and the etiology of preeclampsia.
AB  - BACKGROUND: A current theory holds that oxidative stress, ie, an imbalance
      between maternal prooxidants and antioxidants, is a component of preeclampsia. It
      is uncertain whether such an imbalance occurs before clinical recognition of the
      syndrome or whether it is related to diet. OBJECTIVE: We measured urinary
      excretion of the isoprostane 8-iso-prostaglandin F(2alpha), which is an indicator
      of oxidative damage to lipids, and the total antioxidant power, which is a global
      measure of antioxidant status, at the entry to prenatal care. We also examined
      the relation of these indexes to diet during pregnancy. DESIGN: A cohort of 307
      gravidae from Camden, NJ, was studied from entry to prenatal care (at 15.0 +/-
      0.49 wk gestation). Measures of the maternal diet were obtained by 24-h recall.
      RESULTS: Risk of preeclampsia was increased 5-fold with higher urinary
      isoprostane excretion and decreased 3-fold with higher total antioxidant power.
      Over the course of pregnancy, there were significant trends for an association of
      higher isoprostane excretion with increased consumption of energy-adjusted fat,
      polyunsaturated fat, and polyunsaturated fatty acids (n-3, n-6, and linoleic and
      linolenic fatty acids), whereas total antioxidant power was not related to diet.
      CONCLUSIONS: Increased urinary excretion of isoprostane and decreased antioxidant
      production is an imbalance that is consistent with oxidative stress, and it
      precedes clinical recognition of preeclampsia. The maternal diet is an underlying
      factor that provides an environment for free radical generation.

PMID- 15941893
TI  - Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects
      on feeding tolerance and infectious morbidity: a randomized controlled trial.
AB  - BACKGROUND: Glutamine depletion has negative effects on the functional integrity
      of the gut and leads to immunosuppression. Very-low-birth-weight (VLBW) infants
      are susceptible to glutamine depletion because nutrition is limited in the first
      weeks of life. OBJECTIVE: The objective was to determine the effect of glutamine
      enriched enteral nutrition on feeding tolerance, infectious morbidity, and short
      term outcome in VLBW infants. DESIGN: In a double-blind randomized controlled
      trial, VLBW infants (gestational age <32 wk or birth weight <1500 g) were
      allocated to receive enteral glutamine supplementation (0.3 g . kg(-1) . d(-1))
      or isonitrogenous control supplementation (alanine) between days 3 and 30 of
      life. The supplementations were added to breast milk or to preterm formula. The
      primary endpoint for the study was time to full enteral feeding. Secondary
      endpoints were other variables of feeding tolerance, infectious morbidity, and
      short-term outcome. RESULTS: Baseline patient and nutritional characteristics
      were not significantly different in the glutamine-supplemented (n = 52) and the
      control (n = 50) groups. The median time to full enteral feeding was 13 d (range:
      7-31 d) in the glutamine-supplemented group and 13 d (range: 6-35 d) in the
      control group (hazard ratio: 1.19; 95% CI: 0.79, 1.79; P = 0.40). In the
      glutamine-supplemented group, 26 of 52 infants (50%) had >/=1 serious infection
      compared with 38 of 50 (76%) in the control group (odds ratio: 0.32; 95% CI:
      0.14, 0.74; P = 0.008). Other variables of feeding tolerance and short-term
      outcome were not significantly different between groups. CONCLUSIONS: Glutamine
      enriched enteral nutrition did not improve feeding tolerance or short-term
      outcome in VLBW infants. However, infectious morbidity was significantly lowered
      in infants who received glutamine-enriched enteral nutrition.

PMID- 15941894
TI  - Severely dysregulated disposal of postprandial triacylglycerols exacerbates
      hypertriacylglycerolemia in HIV lipodystrophy syndrome.
AB  - BACKGROUND: The pathogenesis of hypertriacylglycerolemia, a characteristic
      feature of HIV lipodystrophy syndrome (HLS), is incompletely understood. One
      mechanism is accelerated lipolysis in the fasted state, but the severity of the
      hypertriacylglycerolemia suggests that additional underlying abnormalities may
      exist in the disposal of dietary fat. OBJECTIVE: Our objective was to investigate
      abnormalities in dietary fat disposal in the pathogenesis of
      hypertriacylglycerolemia in HLS. DESIGN: We studied 6 nondiabetic men with HLS
      and 6 men without HIV matched for age and body mass index as control subjects for
      8 h after consumption of an isocaloric meal containing 2 g labeled
      [(13)C(3)]tripalmitin. Chylomicron-triacylglycerol disposal was estimated from
      labeled [(13)C(1)]palmitate in the plasma chylomicron fraction, and
      [(13)C(1)]palmitate oxidation was estimated from the (13)CO(2) enrichment in the
      breath and CO(2) production, over 8 h after the meal. RESULTS: HLS patients had
      significantly elevated concentrations of fasting plasma triacylglycerols in both
      chylomicron (x + SE: 100.3 +/- 49.5 compared with 29.2 +/- 2.2 mg/dL; P < 0.01)
      and VLDL (82.4 +/- 39.0 compared with 10.8 +/- 2.8 mg/dL; P < 0.01) fractions.
      Chylomicron-triacylglycerol-derived [(13)C(1)]palmitate disposal was markedly
      lower in the HLS patients (3.09 +/- 0.41 compared with 6.42 +/- 0.18 mmol
      [(13)C(1)]palmitate/8 h; P < 0.001) in the 8-h postmeal period. Further, HLS
      patients had lowered storage of chylomicron-triacylglycerols (0.74 +/- 0.38
      compared with 5.05 +/- 0.16 mmol; P < 0.0001) and elevated plasma
      [(13)C(1)]palmitate concentrations (2.01 +/- 0.27 compared with 1.18 +/- 0.16
      mmol; P < 0.05) 8 h after the meal. CONCLUSIONS: Patients with HLS have key
      defects that markedly impair postprandial disposal and storage of chylomicron
      triacylglycerols. These defects contribute significantly to
      hypertriacylglycerolemia in HLS.

PMID- 15941895
TI  - Carbohydrate intake and glycemic index in relation to the odds of early cortical
      and nuclear lens opacities.
AB  - BACKGROUND: Animal studies suggest a role for dietary carbohydrate in
      cataractogenesis. However, few published human studies have evaluated
      associations between carbohydrate nutrition and lens opacification. OBJECTIVE:
      Our objective was to test the hypothesis that long-term carbohydrate intake and
      dietary glycemic index are associated with the odds of early cortical and nuclear
      opacities. DESIGN: Subjects were 417 Boston-area members of the Nurses' Health
      Study cohort aged 53-73 y. Dietary information was based on an average from 5
      semiquantitative food-frequency questionnaires collected over a 14-y period.
      Opacities were assessed by using the Lens Opacity Classification System III (LOCS
      III). We used eyes (n = 711) as the unit of analysis and generated odds ratios by
      using a generalized estimating approach to logistic regression to account for the
      lack of independence between the 2 eyes of each subject. RESULTS: After
      multivariate adjustment, the odds of cortical opacities (LOCS III >/=1.0) among
      women in the highest tertile of carbohydrate intake (>/=200 g/d) was 2.46 times
      (95% CI: 1.30, 4.64; P for trend = 0.005) that among women in the lowest tertile
      (<185 g/d). This association was not affected by adjustment for dietary glycemic
      index, which was not associated with early cortical opacities. Carbohydrate
      nutrition was not associated with the odds of nuclear opacities (LOCS III
      >/=2.5). CONCLUSIONS: These data suggest that carbohydrate quantity, but not
      carbohydrate quality, is associated with early cortical opacities, and that
      neither the quantity nor the quality of dietary carbohydrate affects the risk of
      nuclear opacities in middle-aged women.

PMID- 15941896
TI  - Fruit and vegetable intake and the risk of cataract in women.
AB  - BACKGROUND: Prospective data on cataract in relation to total fruit and vegetable
      intake are limited. OBJECTIVE: We aimed to examine whether higher fruit and
      vegetable intake reduces the risk of cataract and cataract extraction in a large,
      prospective cohort of women. DESIGN: Fruit and vegetable intake was assessed at
      baseline in 1993 among 39 876 female health professionals with the use of a
      validated, semiquantitative food-frequency questionnaire. A total of 35 724 of
      these women were free of a diagnosis of cataract at baseline and were followed
      for incident cataract and cataract extraction. Cataract was defined as an
      incident, age-related lens opacity responsible for a reduction in best-corrected
      visual acuity to 20/30 or worse, based on self-report confirmed by medical record
      review. Individuals, rather than eyes, were the unit of analysis. RESULTS: During
      an average of 10 y of follow-up, 2067 cataracts and 1315 cataract extractions
      were confirmed. Compared with women in the lowest quintile of fruit and vegetable
      intake, women with higher intakes had modest 10-15% reduced risks of cataract (P
      for trend < 0.05). For cataract extraction, no significant inverse trend was
      observed (P for trend = 0.12). CONCLUSION: These prospective data suggest that
      high intake of fruit and vegetables may have a modest protective effect on
      cataract.

PMID- 15941897
TI  - Protein consumption is an important predictor of lower limb bone mass in elderly
      women.
AB  - BACKGROUND: The effect of protein intake on bone density is uncertain, and
      evidence exists for beneficial effects of both low and high protein intakes.
      OBJECTIVE: The objective was to study the relation between protein consumption
      and bone mass in elderly women with allowance for other lifestyle factors
      affecting bone metabolism. DESIGN: We conducted a cross-sectional and
      longitudinal study of a population-based sample of 1077 women aged 75 +/- 3 y. At
      baseline, protein consumption was measured with a food-frequency questionnaire,
      and bone mass and structure were measured by using quantitative ultrasound of the
      heel. One year later, hip bone mineral density (BMD) was measured by using dual
      energy X-ray absorptiometry. RESULTS: Subjects consumed a mean (+/-SD) of 80.5 +/
      27.8 g protein/d (1.19 +/- 0.44 g protein/kg body wt). Regression analysis
      showed a positive correlation between protein intake and qualitative ultrasound
      of the heel and BMD after adjustment for age, body mass index, and other
      nutrients. The dose-response effect was best characterized by protein consumption
      expressed in tertiles, such that subjects in the lowest tertile (<66 g protein/d)
      had significantly lower qualitative ultrasound of the heel (1.3%) and hip BMD
      (2.6%) than did the subjects in the higher tertiles (>87 g protein/d).
      CONCLUSION: These data suggest that protein intakes for elderly women above
      current recommendations may be necessary to optimize bone mass.

PMID- 15941898
TI  - Interactions between the -514C->T polymorphism of the hepatic lipase gene and
      lifestyle factors in relation to HDL concentrations among US diabetic men.
AB  - BACKGROUND: Low plasma HDL-cholesterol concentrations are a hallmark of diabetic
      dyslipidemia. A common polymorphism (-514C-->T) of the hepatic lipase gene
      (LIPC), which accounts for up to 30% of the variation in hepatic lipase activity,
      has been associated with low hepatic lipase activity and high HDL-cholesterol
      concentrations. OBJECTIVE: We examined the association between this polymorphism
      and plasma HDL-cholesterol concentrations and evaluated whether this association
      was modified by adiposity and dietary fat intake. DESIGN: We followed men aged 40
      75 y who participated in the Health Professionals Follow-Up Study in 1986. Among
      18 159 men who returned blood samples by 1994, 780 had confirmed type 2 diabetes
      at blood drawing or during follow-up to 1998 and were free of cardiovascular
      disease at blood drawing. RESULTS: After adjustment for age, smoking, alcohol
      consumption, fasting status, glycated hemoglobin concentration, physical
      activity, and body mass index, HDL-cholesterol concentrations were significantly
      higher in men with the C/T or T/T genotype than in those with the C/C genotype
      (adjusted x: 40.9 and 38.8 mg/dL, respectively; P = 0.01). We observed
      significant LIPC -514 polymorphism x body mass index and LIPC -514 polymorphism x
      saturated fat intake interactions for HDL-cholesterol concentrations (P = 0.003
      for both). The T allele was associated with higher HDL-cholesterol concentrations
      only in men who were not overweight or who had higher saturated fat intake.
      CONCLUSION: Our study suggests that the effects of -514C-->T of the LIPC gene on
      HDL concentrations were modified by saturated fat intake and obesity.

PMID- 15941899
TI  - Transcobalamin 776C->G polymorphism negatively affects vitamin B-12 metabolism.
AB  - BACKGROUND: A common genetic polymorphism [transcobalamin (TC) 776C-->G] may
      affect the function of transcobalamin, the protein required for vitamin B-12
      cellular uptake and metabolism. Remethylation of homocysteine is dependent on the
      production of 5-methyltetrahydrofolate and adequate vitamin B-12 for the
      methionine synthase reaction. OBJECTIVES: The objectives were to assess the
      influence of the TC 776C--> G polymorphism on concentrations of the
      transcobalamin-vitamin B-12 complex (holo-TC) and to determine the combined
      effects of the TC 776C-->G and methylenetetrahydrofolate reductase (MTHFR) 677C-
      >T polymorphisms and vitamin B-12 status on homocysteine concentrations. DESIGN:
      Healthy, nonpregnant women (n = 359; aged 20-30 y) were screened to determine
      plasma vitamin B-12, serum holo-TC, and plasma homocysteine concentrations and TC
      776C-->G and MTHFR 677C-->T genotypes. RESULTS: The serum holo-TC concentration
      for women with the variant TC 776 GG genotype was significantly different (P =
      0.0213) from that for subjects with the CC genotype (74 +/- 37 and 87 +/- 33
      pmol/L, respectively). An inverse relation was observed between plasma
      homocysteine concentrations and both serum holo-TC (P </= 0.0001) and plasma
      vitamin B-12 (P </= 0.0001) concentrations, regardless of genotype. CONCLUSIONS:
      These data suggest that the TC 776C-->G polymorphism negatively affects the serum
      holo-TC concentration and provide additional evidence that vitamin B-12 status
      modulates the homocysteine concentration in this population.

PMID- 15941900
TI  - Effect of protein supplementation during a 6-mo strength and conditioning program
      on insulin-like growth factor I and markers of bone turnover in young adults.
AB  - BACKGROUND: Exercise is beneficial for bone when adequate nutrition is provided.
      The role of protein consumption in bone health, however, is controversial.
      OBJECTIVE: The objective was to ascertain the effect of high protein intake on
      insulin-like growth factor I (IGF-I) and markers of bone turnover during 6 mo of
      exercise training. DESIGN: Fifty-one subjects aged 18-25 y (28 men, 23 women)
      received a protein supplement (42 g protein, 24 g carbohydrate, 2 g fat) or a
      carbohydrate supplement (70 g carbohydrate) twice daily. Exercise consisted of
      alternating resistance training and running 5 times/wk. Plasma concentrations of
      IGF-I, insulin-like growth factor-binding protein 3, serum bone alkaline
      phosphatase, and urinary N-telopeptide collagen crosslink (NTx) concentrations
      were measured at 0, 3, and 6 mo after 24 h without exercise and a 12-h fast.
      RESULTS: Three-day diet records indicated no difference in energy intake between
      the groups. Average protein intakes after supplementation began in the protein
      and carbohydrate groups were 2.2 +/- 0.1 and 1.1 +/- 0.1 g/kg, respectively (P <
      0.001). The increase in plasma IGF-I was greater in the protein group than in the
      carbohydrate group (time x supplement interaction, P = 0.01). There were no
      significant changes over time or significant differences by supplement in plasma
      insulin-like growth factor-binding protein 3 (44 and 40 kDa). Serum bone alkaline
      phosphatase increased significantly over time (P = 0.04) and tended to be higher
      in the protein group than in the carbohydrate group (P = 0.06). NTx
      concentrations changed over time (time and time squared; P < 0.01 for both) and
      were greater in the protein group than in the carbohydrate group (P = 0.04). Men
      had higher NTx concentrations than did women (74.6 +/- 3.4 and 60.0 +/- 3.8
      nmol/mmol creatinine; P = 0.005). CONCLUSION: Protein supplementation during a
      strength and conditioning program resulted in changes in IGF-I concentrations.

PMID- 15941901
TI  - Level of physical activity and adiposity in children: relevance of sedentary
      behaviors.

PMID- 15941902
TI  - Measuring calcium absorption.

PMID- 15941903
TI  - Effects of a gluten-free diet on gastrointestinal symptoms in celiac disease.

PMID- 15941904
TI  - Nutrigenomic explanation for the beneficial effects of fish oil on cognitive
      function.

PMID- 15941907
TI  - Expression of 11beta-hydroxysteroid dehydrogenase type 1 permits regulation of
      glucocorticoid bioavailability by human dendritic cells.
AB  - Glucocorticoids (GCs) exert powerful anti-inflammatory effects that may relate in
      part to their ability to restrict the differentiation and function of dendritic
      cells (DCs). Although these inhibitory effects are dependent upon GCs binding to
      nuclear glucocorticoid receptors (GRs), fine-tuning of GR signaling is achieved
      by prereceptor interconversion of cortisol that binds GRs with high affinity and
      cortisone that does not. We show for the first time that human monocyte-derived
      DCs are able to generate cortisol as a consequence of up-regulated expression of
      the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). Immature DCs
      demonstrate selective enhancement of 11beta-HSD1 reductase activity, leading to
      increased conversion of inactive cortisone to active cortisol. Enhancement of GC
      bioavailability is maintained or increased upon terminal differentiation induced
      by signals associated with innate immune activation. In marked contrast,
      maturation induced by CD40 ligation leads to a sharp reduction in cortisol
      generation by DCs. The differentiation of DCs from monocyte precursors is
      inhibited at physiologic concentrations of inactive cortisone, an effect that
      requires activity of the 11beta-HSD1 enzyme. In conclusion, prereceptor
      regulation of endogenous GCs appears to be an important determinant of DC
      function and represents a potential target for therapeutic manipulation.

PMID- 15941905
TI  - Chemokine-induced recruitment of genetically modified bone marrow cells into the
      CNS of GM1-gangliosidosis mice corrects neuronal pathology.
AB  - Bone marrow cells (BMCs) could correct some pathologic conditions of the central
      nervous system (CNS) if these cells would effectively repopulate the brain. One
      such condition is G(M1)-gangliosidosis, a neurodegenerative glycosphingolipidosis
      due to deficiency of lysosomal beta-galactosidase (beta-gal). In this disease,
      abnormal build up of G(M1)-ganglioside in the endoplasmic reticulum of brain
      cells results in calcium imbalance, induction of an unfolded protein response
      (UPR), and neuronal apoptosis. These processes are accompanied by the
      activation/proliferation of microglia and the production of inflammatory
      cytokines. Here we demonstrate that local neuroinflammation promotes the
      selective activation of chemokines, such as stromal-cell-derived factor 1 (SDF
      1), macrophage inflammatory protein 1-alpha (MIP-1alpha), and MIP-1beta, which
      chemoattract genetically modified BMCs into the CNS. Mice that underwent bone
      marrow transplantation showed increased beta-gal activity in different brain
      regions and reduced lysosomal storage. Decreased production of chemokines and
      effectors of the UPR as well as restoration of neurologic functions accompanied
      this phenotypic reversion. Our results suggest that beta-gal-expressing bone
      marrow (BM)-derived cells selectively migrate to the CNS under a gradient of
      chemokines and become a source of correcting enzyme to deficient neurons. Thus, a
      disease condition such as G(M1)-gangliosidosis, which is characterized by
      neurodegeneration and neuroinflammation, may influence the response of the CNS to
      ex vivo gene therapy.

PMID- 15941906
TI  - A critical role for 14-3-3zeta protein in regulating the VWF binding function of
      platelet glycoprotein Ib-IX and its therapeutic implications.
AB  - The platelet receptor for von Willebrand factor (VWF), glycoprotein (GP) Ib-IX,
      mediates platelet adhesion and activation. The cytoplasmic domains of the GPIb
      alpha and beta subunits contain binding sites for the phosphorylation-dependent
      signaling molecule, 14-3-3zeta. Here we show that a novel membrane-permeable
      inhibitor of 14-3-3zeta-GPIbalpha interaction, MPalphaC, potently inhibited VWF
      binding to platelets and VWF-mediated platelet adhesion under flow conditions.
      MPalphaC also inhibited VWF-dependent platelet agglutination induced by
      ristocetin. Furthermore, activation of the VWF binding function of GPIb-IX
      induced by GPIbbeta dephosphorylation is diminished by mutagenic disruption of
      the 14-3-3zeta binding site in the C-terminal domain of GPIbalpha, mimicking
      MPalphaC-induced inhibition, indicating that the inhibitory effect of MPalphaC is
      likely to be caused by disruption of 14-3-3zeta binding to GPIbalpha. These data
      suggest a novel 14-3-3zeta-dependent regulatory mechanism that controls the VWF
      binding function of GPIb-IX, and also suggest a new type of antiplatelet agent
      that may be potentially useful in preventing or treating thrombosis.

PMID- 15941908
TI  - TGF-beta in allogeneic stem cell transplantation: friend or foe?
AB  - Donor treatment with granulocyte-colony-stimulating factor (G-CSF) attenuates the
      ability of donor T cells to induce acute graft-versus-host disease (aGVHD) but
      increases the severity of chronic GVHD (cGVHD). We investigated the role of the
      regulatory cytokine transforming growth factor beta (TGF-beta) in this paradox in
      well-established murine models of aGVHD and cGVHD wherein recipients undergo
      transplantation with splenocytes from donors treated with G-CSF. Neutralization
      of TGF-beta after stem-cell transplantation (SCT) significantly increased the
      severity of aGVHD, and the concurrent prevention of interleukin-10 (IL-10)
      production further exaggerated this effect. Early after SCT, donor T cells were
      the predominant source of TGF-beta and were able to attenuate aGVHD in a TGF-beta
      dependent fashion. Although the neutralization of TGF-beta augmented the
      proliferation and expansion of donor T cells after SCT, it paradoxically impaired
      cellular cytotoxicity to host antigens and associated graft-versus-leukemia (GVL)
      effects. In cGVHD, neutralization of TGF-beta from day 14 after SCT attenuated
      histologic abnormalities, and CD11b+ mononuclear cells infiltrating
      sclerodermatous skin produced 50-fold more TGF-beta than corresponding T cells.
      Thus, though the production of TGF-beta by donor T cells early after
      transplantation attenuates aGVHD and is required for optimal GVL, the production
      of TGF-beta late after SCT is preferentially from mononuclear cells and mediates
      cGVHD. These data have important implications for the timing of therapeutic TGF
      beta neutralization to prevent cGVHD after allogeneic SCT.

PMID- 15941909
TI  - Motility, proliferation, and egress to the circulation of human AML cells are
      elastase dependent in NOD/SCID chimeric mice.
AB  - The role of the proteolytic enzyme elastase in motility and proliferation of
      leukemic human acute myeloblastic leukemia (AML) cells is currently unknown. We
      report a correlation between abnormally high levels of elastase in the blood of
      AML patients and the number of leukemic blast cells in the circulation. In AML
      cells, we observed expression of cell-surface elastase, which was regulated by
      the chemokine stromal cell-derived factor-1 (SDF-1). In vitro inhibition of
      elastase prevented SDF-1-induced cell polarization, podia formation, and reduced
      migration of human AML cells as well as their adhesion. Elastase inhibition also
      significantly impaired in vivo homing of most human AML cells to the bone marrow
      (BM) of nonobese diabetic-severe combined immunodeficient (NOD/SCID)/beta-2
      microglobulin knock-out (B2m null) mice that underwent transplantation. Moreover,
      in vitro proliferation of AML cells was elastase dependent. In contrast,
      treatment with elastase inhibitor enhanced the proliferation rate of human cord
      blood CD34+ cells, including primitive CD34+/CD38- cells, and their in vivo
      homing. Finally, NOD/SCID mice previously engrafted with human AML cells and
      treated with elastase inhibitor had significantly reduced egress of leukemic
      cells into the circulation. Taken together, our data demonstrate that human AML
      cells constitutively secrete and express SDF-1-dependent cell-surface elastase,
      which regulates their migration and proliferation.

PMID- 15941910
TI  - Vav proteins regulate peripheral B-cell survival.
AB  - Mice lacking all 3 Vav proteins fail to produce significant numbers of
      recirculating follicular or marginal zone B cells. Those B cells that do mature
      have shortened lifespans. The constitutive nuclear factor-kappaB (NF-kappaB)
      activity of resting naive B cells required Vav function and expression of
      cellular reticuloendotheliosis (c-Rel). Rel-A was reduced in Vav-deficient B
      cells. Furthermore, expression of the NF-kappaB-regulated antiapoptotic genes A1
      and Bcl-2 was reduced in mature Vav-deficient B cells. Overexpression of Bcl-2
      restored the number of mature follicular B cells in the spleens of Vav-deficient
      mice. When activated by B-cell receptor (BCR) cross-linking, Vav-deficient B
      cells failed to activate NF-kappaB. Vav proteins thus regulate an NF-kappaB
      dependent survival signal in naive B cells and are required for NF-kappaB
      function after BCR cross-linking.

PMID- 15941911
TI  - Fas signal links innate and adaptive immunity by promoting dendritic-cell
      secretion of CC and CXC chemokines.
AB  - Dendritic cells (DCs) and chemokines are important in linking innate and adaptive
      immunity. We previously reported that Fas ligation induced interleukin 1beta (IL
      1beta)-dependent maturation and IL-1beta-independent survival of DCs, with
      extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB)
      signaling pathways involved, respectively. We describe here that Fas ligation
      induced DCs to rapidly produce both CXC and CC chemokines, including macrophage
      inflammatory protein 2 (MIP-2), MIP-1alpha, MIP-1beta, monocyte chemoattractant
      protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and
      secreted), and TARC (thymus and activation-regulated chemokine), resulting in
      enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or
      by its supernatant in vitro. These chemokines work synergistically in
      chemoattraction of neutrophils and T cells with MIP-2 more important for
      neutrophils, MIP-1alpha and TARC more important for T cells. Moreover, Fas
      ligated DCs increased endocytosis by neutrophils and activation and proliferation
      of antigen-specific naive T cells. Fas ligation-induced DC secretion of
      chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK
      activation and is ERK, but not NF-kappaB, dependent. Activation of caspases,
      including caspase 1, but not IL-1 autocrine action, is involved in this process.
      These data indicate that Fas signaling provides a key link between innate
      response and adaptive immunity by promoting DC chemokine production.

PMID- 15941912
TI  - Paradoxic inhibition of human natural interferon-producing cells by the
      activating receptor NKp44.
AB  - Natural killer (NK) cell-mediated cytotoxicity is triggered by multiple
      activating receptors associated with the signaling adaptor protein DNAX
      activation protein 12/killer cell-activating receptor-associated protein
      (DAP12/KARAP). Here, we show that one of these receptors, NKp44, is present on a
      subset of natural interferon-producing cells (IPCs) in tonsils. NKp44 expression
      can also be induced on blood IPCs after in vitro culture with interleukin 3 (IL
      3). Crosslinking of NKp44 does not trigger IPC-mediated cytotoxicity but,
      paradoxically, inhibits interferon alpha (IFN-alpha) production by IPCs in
      response to cytosine-phosphate-guanosine (CpG) oligonucleotides. We find that
      IPCs in tonsils are in close contact with CD8+ T cells and demonstrate that a
      subset of memory CD8+ T cells produces IL-3. Therefore, IL-3-mediated induction
      of NKp44 on IPCs may be an important component of the ongoing crosstalk between
      the innate and adaptive immune response that allows memory CD8+ T cells to
      control the IPC response to virus.

PMID- 15941913
TI  - How I treat idiopathic thrombocytopenic purpura (ITP).

PMID- 15941914
TI  - MHC class II/CD38/CD9: a lipid-raft-dependent signaling complex in human
      monocytes.
AB  - Despite a lack of signaling motifs in their cytoplasmic domain, major
      histocompatibility complex (MHC) class II molecules trigger a variety of
      intracellular signals that regulate antigen-presenting cell function. They thus
      may use associated effector molecules as demonstrated on B cells and dendritic
      cells. The starting point of this study comes from our previous work, which
      demonstrated that the ecto-enzyme CD38 is functionally linked to MHC class II
      molecules. We report that CD38 and human leukocyte antigen-DR (HLA-DR) are
      functionally and physically associated in lipid rafts microdomains of cellsurface
      monocytes and that the integrity of these domains is necessary for the HLA-DR and
      CD38 signaling events. Moreover, we identified the tetraspanin CD9 molecule as a
      partner of the CD38/HLA-DR complex and demonstrated that HLA-DR, CD38, and CD9
      share a common pathway of tyrosine kinase activation in human monocytes. The
      analysis of conjugate formation between monocytes presenting superantigen and T
      cells shows the active participation of CD9 and HLA-DR on the monocyte surface.
      Together, these observations demonstrate the presence of a CD38 and HLA-DR
      signaling complex within tetraspanin-containing lipid rafts and the functional
      impact of their molecular partner CD9 in antigen presentation.

PMID- 15941915
TI  - In vivo delivery of caspase-8 or Fas siRNA improves the survival of septic mice.
AB  - Although studies have shown increased evidence of death receptor-driven apoptosis
      in intestinal lymphoid cells, splenocytes, and the liver following the onset of
      polymicrobial sepsis, little is known about the mediators controlling this
      process or their pathologic contribution. We therefore attempted to test the
      hypothesis that the hydrodynamic administration of small interfering RNA (siRNA)
      against the death receptor, Fas or caspase-8, should attenuate the onset of
      morbidity and mortality seen in sepsis, as produced by cecal ligation and
      puncture (CLP). We initially show that in vivo administration of green
      fluorescent protein (GFP) siRNA in GFP transgenic mice results in a decrease in
      GFP fluorescence in most tissues. Subsequently, we also found that treating
      septic nontransgenic mice with siRNA targeting Fas or caspase-8 but not GFP (used
      as a control here) decreased the mRNA, in a sustained fashion up to 10 days, and
      protein expression of Fas and caspase-8, respectively. In addition, transferase
      mediated dUTP (deoxyuridine triphosphate) nick end labeling (TUNEL) and active
      caspase-3 analyses revealed a decrease in apoptosis in the liver and spleen but
      not the thymus following siRNA treatment. Indices of liver damage were also
      decreased. Finally, the injection of Fas or caspase-8 given not only 30 minutes
      but up to 12 hours after CLP significantly improved the survival of septic mice.

PMID- 15941916
TI  - Impact of tumor Epstein-Barr virus status on presenting features and outcome in
      age-defined subgroups of patients with classic Hodgkin lymphoma: a population
      based study.
AB  - The association between tumor Epstein-Barr virus (EBV) status and clinical
      outcome in Hodgkin lymphoma (HL) is controversial. This population-based study
      assessed the impact of EBV status on survival in age-stratified cohorts of adults
      with classic HL (cHL). Data from 437 cases were analyzed with a median follow-up
      of 93 months. Overall survival (OS) was significantly better for EBV-negative
      compared with EBV-positive patients (P < .001), with 5-year survival rates of 81%
      and 66%, respectively; disease-specific survival (DSS) was also greater for EBV
      negative patients (P = .03). The impact of EBV status varied with age at
      diagnosis. In patients aged 16 to 34 years, EBV-associated cases had a survival
      advantage compared with EBV-negative cases, but differences were not
      statistically significant (P = .21). Among patients 50 years or older, EBV
      positivity was associated with a significantly poorer outcome (P = .003). Excess
      deaths occurred in EBV-positive patients with both early- and advanced-stage
      disease. In multivariate analysis of OS in the older patients, EBV status
      retained statistical significance after adjusting for the effects of sex, stage,
      and B symptoms (P = .01). Impaired immune status may contribute to the
      development of EBV-positive cHL in older patients, and strategies aimed at
      boosting the immune response should be investigated in the treatment of these
      patients.

PMID- 15941917
TI  - Impaired Ig class switch in mice deficient for the X-linked lymphoproliferative
      disease gene Sap.
AB  - X-linked lymphoproliferative disease (XLP) is characterized by abnormal immune
      responses to Epstein-Barr virus attributed to inactivating mutations of the SAP
      gene. Previous studies showed immunoglobulin E (IgE) deficiency and low serum IgG
      levels in Sap-deficient mice before and after viral infections, which are
      associated with impaired CD4+ T-helper function. In the present work, we find
      that signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) is
      expressed in B cells and this expression is down-regulated after stimulation with
      lipopolysaccharide (LPS) and interleukin 4 (IL-4). We demonstrate that B cells
      from Sap-deficient mice exhibit reduced IgG and IgA production in vitro. This
      impairment correlates with decreased circular transcript levels of Ialpha,
      Igamma2a, Igamma2b, and Igamma3 after stimulation, which indicate a defective Ig
      switch recombination in Sap-deficient B cells. While XLP is believed to cause
      defects in T, natural killer T (NKT), and natural killer (NK) cells, our results
      indicate that B cells are also affected.

PMID- 15941918
TI  - The expression and the regulatory role of OX40 and 4-1BB heterodimer in activated
      human T cells.
AB  - OX40 and 4-1BB are members of the tumor necrosis factor (TNF) family of
      costimulatory receptors whose signaling is important for differential immune
      responses mediated by CD4+ or CD8+ T cells. Although activated T cells may
      acquire OX40/4-1BB double-positive phenotype and signaling from each receptor is
      expected to influence cell functions, the relevance between OX40 and 4-1BB has
      never been investigated before. While we were investigating the expression of
      OX40 and 4-1BB on activated human T cells, we found that they colocalize. The
      study of receptor gene-transfected cells showed that both receptors coendocytose
      and the complex of OX40 and 4-1BB was detected by specific ligands or antibodies
      (Abs). The heterodimer of OX40 and 4-1BB was identified by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE) under nonreduced conditions and was
      associated with the tumor receptor-associated factor (TRAF) family proteins in a
      unique manner. Furthermore, the stimulation of OX40/4-1BB rendered cells
      sensitive to apoptosis induced by TNF-alpha that accompanied reduced activation
      of nuclear factor-kappaB (NF-kappaB). Finally, the OX40/4-1BB stimulation
      repressed the mitogen response in activated CD25+CD4+ T cells and preactivated
      CD8+ T cells. Thus, the OX40/4-1BB heterodimer appears to represent a unique
      regulatory receptor in activated T cells.

PMID- 15941919
TI  - Coexistence of Kallmann syndrome and complete androgen insensitivity in the same
      patient.
AB  - Kallmann syndrome (KS) is a developmental disease that combines hypogonadotropic
      hypogonadism and anosmia/hyposmia. Other congenital abnormalities may also
      coexist. This present report describes two sisters, aged 13 and 12 years, born
      from Lebanese consanguineous parents. The two sisters have complete androgen
      insensitivity (normal female appearance and an XY karyotype) due to a novel
      mutation, a C-to-G transversion in intron 2 of the androgen receptor gene,
      resulting in an aberrant splicing leading to an insertion of 66 nucleotides in
      the mRNA. In addition, the older sister has KS, together with synkinesia and
      multiple skeletal abnormalities, mainly kyphosis, vertebral abnormalities, and
      short right hand and feet. Her testosterone, FSH and LH levels were very low
      compared with her younger sister. No mutation in the KAL1 and FGFR1/KAL2 genes
      were found. This unique report raises the possibility of an autosomal recessive
      or X-linked form of KS with new phenotypic expression.

PMID- 15941920
TI  - Sympatho-vagal control of heart rate variability in patients treated with
      suppressive doses of L-thyroxine for thyroid cancer.
AB  - OBJECTIVE: This study aimed to analyze the autonomic control of heart rate
      variability (HRV) in subjects receiving chronic l-thyroxine (l-T4) treatment
      after total thyroidectomy and (131)I therapy for differentiated thyroid
      carcinoma. METHODS: Blood pressure (BP) and sympatho-vagal activity (evaluated by
      power spectral analysis (PSA) of time-domain parameters of HRV) were studied in
      clinostatism and after orthostatism in 24 healthy controls, and in 12 patients
      taking l-T4 (125-200 mug/day) to maintain serum TSH levels at <0.01 muIU/ml. The
      study of HRV by PSA is a non-invasive method of analyzing sympatho-vagal control
      of HRV by quantifying high-frequency (HF) (0.15-0.4 Hz) and low-frequency (LF)
      (0.04-0.15 Hz) powers. RESULTS: Patients on L-T4 treatment had undetectable TSH
      levels, serum free T4 (fT4) above the normal range or at the upper limit in one
      case, and normal free tri-iodothyronine (fT3) levels. Heart rate and R-R
      intervals were not different in the two groups, both in clinostatism and in
      ortostatism. Systolic and mean BP were higher in patients than in controls and
      were inversely correlated with actual serum fT4 levels. During clinostatism,
      thyroid patients showed significantly lower LF power (P = 0.035), LF/(LF + HF) (P
      = 0.008) and LF/HF (P = 0.01) than controls. When patients moved from lying to
      standing, there was a significantly different decrease in orthostatic LF power (P
      = 0.001), LF/(LF + HF) (P = 0.044) and LF/HF (P = 0.047) versus controls.
      CONCLUSIONS: Changes in autonomic control of HRV, characterized by decreased
      sympathetic activity and impaired sympatho-vagal balance with preserved vagal
      tone, are detectable in patients with hyperthyroxinemia due to suppressive l-T4
      therapy and increased systolic and mean, but not diastolic, BP.

PMID- 15941921
TI  - Factors influencing cure by transsphenoidal selective adenomectomy in paediatric
      Cushing's disease.
AB  - OBJECTIVE: Early diagnosis and effective treatment of paediatric Cushing's
      disease (CD) is necessary to minimise associated morbidity. Accepted first-line
      treatment is selective transsphenoidal microadenomectomy (TSS), which can be
      technically difficult, and cure rates vary considerably between centres. In our
      paediatric CD patient group we have assessed the possible factors which may
      influence cure by TSS. SUBJECTS AND METHODS: From 1983-2004, 27 paediatric
      patients (16 males, 11 females; mean age+/-s.d., 13.1+/-3.2 yr; range, 6.4-17.8
      yr) with CD were managed in our centre and underwent TSS. Sixteen patients (59%),
      seven males and nine females (mean age+/-s.d., 14.2+/-2.5 yr; range, 8.2-17.8
      yr), were cured (post-operative serum cortisol < 50 nM). Eleven patients, nine
      males and two females (mean age+/-s.d., 11.5+/-3.6 yr; range, 6.4-17.8 yr) had
      post-operative cortisol levels above 50 nM (2-20 days), with mean serum cortisol
      levels at 09:00 h of 537 nM (range 269-900 nM) indicating a lack of cure. These
      11 patients received external beam pituitary radiotherapy (RT). One patient with
      a pituitary macroadenoma had a post-operative cortisol level of < 50 nM but 0.8
      yr later showed an elevated cortisol and residual disease. RESULTS: The patients
      cured by TSS alone were significantly older than those not cured (P = 0.038;
      Student's t test). All patients had CT/MRI pituitary imaging: 14 were reported to
      have microadenomas and one macroadenoma, while 12 were reported as normal.
      Bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with i.v.
      corticotropin-releasing hormone (CRH) administration was introduced as a pre
      operative investigation in 1986 and was performed in 21 patients (78%), on
      BSIPSS, 16 (76%) had evidence suggesting pituitary adrenocorticotropic hormone
      (ACTH) secretion (central to peripheral (IPS:P) ACTH ratio after CRH of > or =
      3.0) and 16 (76%) showed lateralisation of ACTH secretion (IPSG of > or = 1.4).
      There was concordance between the BSIPSS finding and the position of the
      microadenoma at surgery in 17/21 (81%) patients. Of the 16 patients showing
      lateralisation of ACTH secretion, 12 (75%) were cured by TSS. Of the four without
      lateralisation of ACTH, suggesting a midline lesion, 3 (75%) were cured by TSS.
      Post-operative pituitary hormone deficiencies in the patients cured by TSS were:
      pan-hypopituitarism 1/16, isolated growth hormone deficiency (GHD) (peak GH on
      glucagon/ITT < 1-17.9 mU/l) 9/16 and diabetes insipidus 3/16. CONCLUSION: Over a
      21-year period selective adenomectomy by TSS cured 59% of all paediatric CD
      patients, with higher age favouring cure. Introduction of BSIPSS resulted in the
      demonstration of a high rate of lateralisation of ACTH secretion consistent with
      the surgical identification of the adenoma, and therefore appears likely to have
      contributed to the higher surgical cure rate.

PMID- 15941922
TI  - Adult height of prepubertal short children born small for gestational age treated
      with GH.
AB  - OBJECTIVE: Human GH (hGH) treatment leads to catch-up growth in children with
      short stature born small for gestational age (SGA). However, long-term efficacy
      and safety results in this patient group remain scarce. The present study
      assessed the efficacy and safety of late childhood treatment with biosynthetic
      hGH (Humatrope) in a group of short children born SGA (height <-2 standard
      deviation scores (SDS)). DESIGN: Patients in this open-label, Phase III,
      multicenter study received a daily hGH dose of 0.067 mg/kg for 2 years, and then
      received no treatment for the following 2 years. After the fourth year on study,
      patients whose height had decreased more than 0.5 SDS but who still showed growth
      potential based on bone age were allowed to resume treatment until they reached
      adult height. METHODS: Height gain SDS was assessed for 11 girls and 24 boys
      (mean age+/-s.d. 9.6+/-0.9 years) at the end of the 2 years of hGH treatment,
      during the subsequent 2-year off-treatment period, and upon reaching adult
      height. RESULTS: At the end of the initial 2-year treatment period, 83% of
      patients had reached a height within the normal range, with a mean increase in
      height SDS vs baseline of 1.3+/-0.3 (P <0.001). Adult heights (n = 20) were
      within the normal range for 50% of patients, and mean height gain from baseline
      was statistically significant (0.7+/-0.8 SDS, P <0.001). Fasting glucose and
      glycosylated hemoglobin levels were not significantly modified during treatment.
      CONCLUSIONS: High-dose hGH treatment for a minimum of 2 years in short children
      born SGA was well tolerated and resulted in a significant increase in adolescent
      and adult height.

PMID- 15941923
TI  - Spontaneous 24-h ghrelin secretion pattern in fasting subjects: maintenance of a
      meal-related pattern.
AB  - OBJECTIVE: Ghrelin stimulates GH release and causes weight gain through increased
      food intake and reduced fat utilization. Ghrelin levels were shown to rise in the
      preprandial period and decrease shortly after meal consumption, suggesting a role
      as a possible meal initiator. However, ghrelin secretion in fasting subjects has
      not yet been studied in detail. DESIGN: 24-h ghrelin profiles were studied in six
      healthy volunteers (three females; 25.5 years; body mass index 22.8 kg/m(2)) and
      compared with GH, insulin and glucose levels. METHODS: Blood samples were taken
      every 20 min during a 24-h fasting period and total ghrelin levels were measured
      by RIA using a polyclonal rabbit antibody. The circadian pattern of ghrelin
      secretion and pulsatility (Cluster analysis) were evaluated. RESULTS: An increase
      and spontaneous decrease in ghrelin were seen at the timepoints of customary
      meals. Ghrelin was secreted in a pulsatile manner with approximately 8 peaks/24
      h. An overall decrease in ghrelin levels was observed during the study period.
      There was no correlation of ghrelin with GH, insulin or blood glucose levels.
      CONCLUSIONS: This pilot study indicates that fasting ghrelin profiles display a
      circadian pattern similar to that described in people eating three times per day.
      In a fasting condition, GH, insulin and glucose do not appear to be involved in
      ghrelin regulation. In addition, we found that ghrelin is secreted in a pulsatile
      pattern. The variation in ghrelin independently of meals in fasting subjects
      supports previous observations that it is the brain that is primarily involved in
      the regulation of meal initiation.

PMID- 15941924
TI  - Mutation analysis of the MCHR1 gene in human obesity.
AB  - OBJECTIVE: The importance of the melanin-concentrating hormone (MCH) system for
      regulation of energy homeostasis and body weight has been demonstrated in
      rodents. We analysed the human MCH receptor 1 gene (MCHR1) with respect to human
      obesity. DESIGN: This consisted of genomic screening of 13.4 kb encompassing the
      MCHR1 in extremely obese German children and adolescents and association analyses
      for two coding single nucleotide polymorphisms (SNPs). To confirm initial
      positive association results, additional association studies and transmission
      disequilibrium tests in further German, Danish, French and American samples were
      conducted. Selected SNPs were investigated using functional in vitro studies and
      reporter gene assays. METHODS: Single-stranded conformation polymorphism
      analysis, re-sequencing, PCR-restriction fragment length polymorphism analyses,
      tetra-primer amplification refractory mutation systems, matrix-assisted laser
      desorption/ionization time of flight mass spectrometry and reporter gene assays
      were carried out as well as measuring inositol phosphate formation, inhibition of
      cAMP formation and activation of p42/44 MAP kinase. RESULTS: We identified 11
      infrequent variations and two SNPs in the MCHR1 coding sequence and 18 SNPs
      (eight novel) in the flanking sequence. Association and transmission
      disequilibrium with obesity were detected for several SNPs in independent study
      groups of German obese children and adolescents and controls. In two German
      samples, encompassing 4056 and 295 individuals, trends towards association with
      obesity were detected. Findings in a second epidemiological German sample and in
      Danish, French and American samples were negative. Functional in vitro studies as
      well as reporter gene assays revealed no significant results. CONCLUSION: Our
      initial association of MCHR1 alleles/haplotype detected might be related to
      juvenile-onset obesity, conditional on a particular genetic and/or environmental
      background. Alternatively, we could not exclude the possibility that the
      initially detected association represented a false positive finding.

PMID- 15941925
TI  - The proatherogenic cytokine interleukin-18 is secreted by human adipocytes.
AB  - OBJECTIVE: Interleukin (IL)-18, an important mediator of innate immunity and
      strong risk factor for the development of cardiovascular disease, was shown
      recently to be elevated in obesity. The aim of our study was to investigate
      whether human adipocytes produce IL-18. METHODS: Human adipose tissue was
      obtained from lean women undergoing elective plastic surgery and from obese
      individuals undergoing laparoscopic surgery (gastric banding). Preadipocytes from
      mammary adipose tissue were isolated and differentiated under defined adipogenic
      conditions. IL-18 expression was analyzed by real-time reverse transcriptase PCR,
      ELISA and immunocytochemistry. RESULTS: Human preadipocytes of all
      differentiation stages spontaneously secreted IL-18. In parallel significant
      amounts of IL-18 mRNA were detected. Freshly isolated mature adipocytes from
      subcutaneous and omental depots also released IL-18. IL-18 release from
      adipocytes from obese donors was about 3-fold higher compared to adipocytes from
      non-obese donors. CONCLUSIONS: We conclude that human adipose tissue produces IL
      18 and thereby contributes to systemic IL-18 concentrations. This finding
      supports the concepts that adipocytes behave as primitive immune cells and that
      IL-18 may mediate some of the detrimental complications of obesity such as
      cardiovascular disease and type 2 diabetes.

PMID- 15941926
TI  - Estimation of the false-negative rate in newborn screening for congenital adrenal
      hyperplasia.
AB  - OBJECTIVE: Newborn screening based on measurement of 17alpha-hydroxyprogesterone
      (17-OHP) in a dried blood spot on filter paper is an effective tool for early
      diagnosis of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase
      deficiency. Its most important rationale is prevention of a life-threatening salt
      wasting (SW) crisis; in moderate forms of CAH, early diagnosis and treatment may
      prevent permanent negative effects of androgen overproduction. Our target was to
      analyse if all CAH patients who had been identified clinically before puberty
      would have been detected by the newborn screening. METHODS: Newborn screening
      cards of 110 CAH patients born between 1988 and 2000 in five Middle-European
      countries and diagnosed prior to puberty (77 SW and 33 moderate) and cards from
      920 random, healthy newborn controls were analysed. CAH screening had not yet
      been introduced during this time. The diagnosis was based on clinical and
      laboratory signs and, in most cases, on CYP21 gene mutation analysis. All 17-OHP
      measurements in dried blood spots were carried out using a time-resolved
      fluoroimmunoassay kit. RESULTS: In the newborn screening blood spots, the median
      of 17-OHP levels was 561 nmol/l (range 91-1404 nmol/l) in subjects with the SW
      form and 40 nmol/l (4-247 nmol/l) in the moderate form. All 77 SW patients would
      have been detected by newborn screening using the recommended cut-off limits (30
      nmol/l). However, 10 of 33 patients with moderate CAH would have been missed. 17
      OHP levels of all controls were below the cut-off. CONCLUSION: Newborn screening
      is efficient for diagnosing the SW form of CAH, but is inappropriate for
      identifying all patients with a moderate form of CAH. It appears that the false
      negative rate is at least one-third in children with the moderate form of CAH.

PMID- 15941927
TI  - Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human
      genital skin fibroblasts and may play an important role in masculinization of
      5alpha-reductase type 2 deficient males.
AB  - OBJECTIVE: 5alpha-reductase enzymes reduce testosterone (T) to the most potent
      androgen dihydrotestosterone (DHT). Two isoenzymes are known to day. While the
      type 2-enzyme (5RII) is predominantly expressed in male genital tissues and
      mutations are known to cause a severe virilization disorder in genetic males, the
      role of the type 1-enzyme (5RI) in normal male androgen physiology is unclear. We
      investigated whether 5RI is transcribed in normal male genital skin fibroblasts
      (GSFs) and if the transcription is regulated by age or by androgens themselves.
      METHODS: GSF from 14 normally virilized males of different ages, ranging from 8
      months to 72 years, obtained at circumcision were cultured. Total RNA was
      isolated after incubation for 48 h with 100 nM T or without androgens. Each
      sample was amplified in triplicate by real-time PCR with porphobilinogen
      desaminase as a housekeeping gene used for semiquantification. Selected cultures
      were analyzed after incubation with 10 and 100 nM T and 1 and 100 nM DHT for 24,
      48 and 120 h. RESULTS: 5RI was transcribed in all investigated samples with a 4.5
      fold variability in the mRNA concentration of different individuals. However,
      neither age-related regulation nor significant influence of T or DHT on the
      transcription rate was discovered. CONCLUSION: Since 5RI is abundantly
      transcribed in GSFs, we hypothesize that this isoenzyme may play important roles
      in the androgen physiology of normally virilized males and may contribute to
      masculinization in 5RII-deficient males at the time of puberty.

PMID- 15941928
TI  - Adequacy of androgen replacement influences bone density response to testosterone
      in androgen-deficient men.
AB  - OBJECTIVE: Androgen deficiency (AD) leads to bone loss and contributes to
      osteoporotic fractures in men. Although low bone mineral density (BMD) in AD men
      is improved by testosterone replacement, the responses vary between individuals
      but the determinants of this variability are not well defined. DESIGN AND
      METHODS: Retrospective review of dual energy X-ray absorptiometry (DEXA) of the
      lumbar spine and proximal femur in men with established AD requiring regular
      androgen replacement therapy (ART). After a DEXA scan all men were treated with
      testosterone implants (800 mg, approximately 6 month intervals). Patients were
      classified as having a congenital, childhood, or post-pubertal onset, as well as
      according to the adequacy of treatment prior to their first DEXA scan as
      untreated, partially treated or well treated. RESULTS: Men with AD requiring
      regular ART (n = 169, aged 46.3+/-1.1 years, range 22-84 years) underwent a DEXA
      scan prior to being treated with testosterone implants (800 mg, approximately 6
      month intervals). In cross-sectional analysis at the time of the first DEXA scan
      untreated men (n = 24) had significantly reduced age-adjusted BMD at all four
      sites (L1-L4, femoral neck, Ward's triangle and trochanter). Well-treated men (n
      = 77) had significantly better age-adjusted BMD at all four sites compared with
      those who were partially treated (n = 66) or untreated (n = 24) with their age
      adjusted BMD being normalized. In a longitudinal assessment of men (n = 60) who
      had two or more serial DEXA scans, at the second DEXA scan after a median of 3
      years, men who were previously partially treated (n = 19) or untreated (n = 11)
      had proportionately greater improvements in BMD, significantly for Ward's
      triangle (P = 0.025) and the trochanter (P = 0.044) compared with men (n = 30)
      previously well treated. CONCLUSIONS: The present study demonstrates a positive
      relationship between adequacy of testosterone replacement and BMD in men with
      overt organic AD. Additionally, the BMD of well-treated AD men approximates that
      of age-matched non-AD controls. The greatest BMD gains are made by those who have
      been either untreated or partially treated, and optimal treatment over time
      (median 3 years) normalizes BMD to the level expected for healthy men of the same
      age.

PMID- 15941929
TI  - Regulation of ghrelin secretion by somatostatin analogs in rats.
AB  - OBJECTIVE: Ghrelin is a hormone present in the plasma in two forms: octanoylated
      and des-octanoylated ghrelin. In pathophysiological conditions such as Prader
      Willi syndrome and ghrelinoma, elevated ghrelin plasma levels are associated with
      pathological obesity. Clinical studies have shown that somatostatin downregulates
      ghrelin plasma levels in healthy volunteers. The aim of this study was to
      investigate the effects of two somatostatin analogues, SOM230 and octreotide, on
      ghrelin secretion in rats. METHODS: Ghrelin secretion was either unstimulated or
      stimulated by overnight fasting. Treatment with SOM230 and octreotide was either
      acute (s.c. injection 1 h before blood sampling) or prolonged (continuous s.c.
      infusion via 14-day osmotic minipumps). RESULTS: Acute treatment with octreotide
      dose-dependently inhibited unstimulated and stimulated secretion of total and
      active ghrelin. SOM230 (30 microg/kg) inhibited active ghrelin in fasted rats.
      Lower doses had no effect. After 7 days of treatment, active ghrelin was strongly
      inhibited by both compounds in fasted animals, with a stronger effect for
      octreotide. Lower inhibition was achieved in fed rats. After 14 days, the
      inhibition with octreotide in fasted rats was lower and SOM230 had no effect.
      Somatostatin receptor expression analysis in the rat glandular stomach revealed a
      predominant sst(1) and sst(2) expression, low expression of sst(3) and sst(4),
      and hardly detectable sst(5) mRNA expression. CONCLUSIONS: Somatostatin analogues
      may be useful for the inhibition of physiologically elevated ghrelin plasma
      levels. This inhibition appears to be mediated by sst(2) receptors in the rat,
      and desensitizes after 14 days of treatment.

PMID- 15941930
TI  - The impact of chronic in vivo glucocorticoid excess on the functional
      characteristics of human skin fibroblasts obtained from patients with endogenous
      Cushing's syndrome.
AB  - OBJECTIVE: Chronic exposure to elevated glucocorticoid (GC) concentrations
      induces detrimental effects in several tissues. In the skin, GCs provoke intense
      alterations on various parameters of the physiology of fibroblasts, cumulatively
      leading to skin atrophy and impaired wound healing. As there are concerns that
      GCs may generate permanent adverse functional changes, we have investigated
      whether chronic in vivo exposure to GC excess results in persisting defects in
      skin fibroblasts. DESIGN AND METHODS: We have studied in vitro primary skin
      fibroblast cultures obtained from patients suffering from endogenous Cushing's
      syndrome (CF), as well as from sex- and age-matched normal donors (NF). The
      following functional parameters were investigated: cell proliferation, secretion
      of collagen, matrix metalloproteinases (MMPs) and their inhibitors (tissue
      inhibitors of metalloproteinases; TIMPs) and contractile capacity. RESULTS: CFs,
      grown under standard culture conditions in the absence of a hypercortisolemic
      milieu, exhibited an increased proliferative capacity and a higher final cell
      culture density compared with NFs. Collagen synthesis, in the absence or presence
      of transforming growth factor-beta, was equal to that of NFs. However, CFs
      secreted comparatively lower levels of MMP-1, MMP-2 and TIMP-1, and nearly equal
      levels of TIMP-2. CFs also exhibited an increased ability to contract gels of
      polymerized collagen. CONCLUSIONS: Collectively, these functional characteristics
      of CFs are in contrast to the known catabolic effects of GCs, and suggest that
      prior exposure to GC excess is not associated with a persisting adverse outcome
      in the functional phenotype of the fibroblasts.

PMID- 15941931
TI  - The utility of three different methods for measuring urinary 18-hydroxycortisol
      in the differential diagnosis of suspected primary hyperaldosteronism.
AB  - OBJECTIVE: Urine 18-hydroxycortisol (18-OHF) measurements are claimed to
      discriminate between primary hyperaldosteronism due to Conn's syndrome/adrenal
      adenoma or idiopathic bilateral adrenal hyperplasia (BAH), and also to identify
      cases of glucocorticoid-suppressible hyperaldosteronism (GSH). We have evaluated
      three urine 18-OHF methods using a panel of urine samples from patients with
      hypertension. DESIGN: Clinical methods comparative study. METHODS: Urine samples
      from patients with primary hyperaldosteronism due to either adenoma (n = 6), BAH
      (n = 6), GSH (n = 9), or essential hypertension (n = 38) were analysed without
      knowledge of the diagnosis using three different methods in different
      laboratories. These included 'in-house' radioimmunoassay (RIA), 'in-house' time
      resolved fluorometric assay (DELFIA), and gas chromatography mass spectrometry
      (GC-MS). RESULTS: The three assays showed good correlation, but there were large
      bias differences: RIA bias was greater than DELFIA which was greater than GC-MS.
      Discrimination between adenoma and BAH patients was best for the DELFIA method,
      with no overlap between results for these two groups. All three methods gave
      significantly elevated results for the GSH group compared with the BAH and
      essential hypertension groups. No assay distinguished BAH from essential
      hypertension. CONCLUSION: Measurement of urine 18-OHF may be a useful additional
      test in the differential diagnosis of primary hyperaldosteronism. The clinical
      diagnostic value of urinary 18-OHF measurements is method-dependent with the
      DELFIA assay having the best discriminatory value.

PMID- 15941932
TI  - The secretion and effect of inhibin A, activin A and follistatin on first
      trimester trophoblasts in vitro.
AB  - OBJECTIVE: The objectives of this study were to investigate the effect of activin
      A and follistatin on first-trimester cytotrophoblast invasion in culture and to
      study the secretion of inhibin A, activin A and follistatin by these cells in
      vitro. DESIGN AND METHODS: Cytotrophoblasts were isolated from human placental
      chorionic villous tissue obtained from 6-8, 8-10 and 10-12 weeks gestation. Cells
      were cultured for 3 days on cell-culture inserts coated with gelatine for
      invasion studies and in 24-well culture plates for secretion studies. The effects
      of activin A (10 ng/ml), follistatin (100 ng/ml), interleukin 1beta (IL-1beta; 10
      ng/ml) and epidermal growth factor (EGF; 10 ng/ml) on cytotrophoblast invasion
      were investigated using a non-radioactive invasion assay. Secretion of inhibin A,
      activin A and follistatin in the presence of EGF, IL-1beta, activin A and
      follistatin were measured using in-house ELISAs. RESULTS AND CONCLUSION: Activin
      A, follistatin and EGF had a significant stimulatory effect on cytotrophoblast
      invasion from 6-10 weeks gestation. IL-1beta had a significant stimulatory effect
      at 8-10 weeks and a significant inhibitory effect on invasion at 10-12 weeks
      gestation. Follistatin also had a significant inhibitory effect on invasion at 10
      12 weeks gestation. In the secretion study, activin A secretion at 8-10 weeks was
      significantly stimulated by IL-1beta and EGF. At 10-12 weeks, follistatin and EGF
      had a significant inhibitory effect on activin A secretion. Follistatin secretion
      was significantly increased in the presence of IL-1beta at 6-8 weeks gestation.
      Inhibin A secretion was not significantly altered by EGF, IL-1beta, activin A and
      follistatin. These results show that activin A promotes invasion of first
      trimester cytotrophoblasts until 10 weeks gestation. There is a difference in the
      control of secretion of these proteins dependent on the gestation, suggesting
      that there is a tight regulation in the function of first-trimester trophoblasts
      depending on the gestational age.

PMID- 15941933
TI  - Predicting adult height in Turner syndrome.

PMID- 15941935
TI  - Cancer prevention: the importance of accurate risk assessment.

PMID- 15941936
TI  - Genetic association studies: time for a new paradigm?

PMID- 15941938
TI  - Publication environment and broad investigation of the genome.

PMID- 15941939
TI  - The reliable identification of disease-gene associations.

PMID- 15941940
TI  - Publication policy or publication bias?

PMID- 15941941
TI  - Reflections on publication criteria for genetic association studies.

PMID- 15941942
TI  - Diet and cancer: the disconnect between epidemiology and randomized clinical
      trials.
AB  - Dietary epidemiology has been highly successful in identifying the responsible
      agent in many diseases, including scurvy, pellagra, blindness, and spinal bifida.
      Case-control, cohort, and ecologic observational studies have consistently
      associated increased consumption of fruits and vegetables with a decreased risk
      for a wide variety of epithelial cancers and, in many cases, specific dietary
      components seem to decrease the risk for a wide array of epithelial cancers. Over
      time, there has been enthusiasm for one or another compounds, such as beta
      carotene in the past and folate currently. Despite the success of translating
      similar epidemiologic observations to clinical benefit in other areas of medicine
      via the crucible of the randomized clinical trial, this strategy has not been
      nearly as successful for cancer. We propose that the inability of nutritional
      epidemiology to identify effective chemopreventive strategies is not just a
      problem of quantitation, but rather that the discipline is usually qualitatively
      incapable of identifying a dietary compound(s) that will be efficacious. One
      needs to consider the following basic questions in trying to understand why
      nutritional epidemiology has not been translated into progress in cancer
      prevention: Why do fruits and vegetable show a consistent protective effect
      against many epithelial cancers in epidemiologic studies? Once a specific dietary
      compound is identified as protective in observational studies, why do most
      subsequent observational studies confirm the effect? Why are dietary epidemiology
      observations frequently not confirmed by the randomized clinical trial? We call
      the identified problems "fishing with only one bait" and the "four-legged stool
      problem." The considerations identified in this analysis offer a number of
      possible solutions to puzzling findings: (a) Fruits and vegetables consistently
      show a protective effect against cancer in observational studies because they
      represent the entire "biological action package." (b) Dietary compounds show a
      protective effect in observational studies, but not in clinical trials, because
      this is an inevitable consequence of one compound being falsely identified as the
      active agent in a system in which multiple agents or multiple interacting
      regulatory molecules underlie the biological effect. The consequences are serious
      for trying to use epidemiology to identify effective nutritional compounds. The
      major conclusion has to be as follows: Supplementation with single dietary
      compounds is rarely going to be as effective as epidemiologic studies suggest; it
      is the biological action package that determines efficacy. Options for how we
      should move forward will be discussed. Dietary observational epidemiology is
      complex and involves many biases and confounders. We need to be more critical in
      the design of large randomized trials based on observational epidemiology or
      analysis. Rules of evidence are frequently ignored or misunderstood although the
      limitations of observational epidemiology are analogous to the problems
      associated with discovery-based research and biomarker identification. We need to
      be much more self-critical in the important and critical assessment of dietary
      compounds and their role in cancer prevention given the very high appeal for this
      approach both within the lay and scientific communities.

PMID- 15941943
TI  - Smoking topography, brand switching, and nicotine delivery: results from an in
      vivo study.
AB  - OBJECTIVE: Exposure to toxins in tobacco smoke is influenced by how a cigarette
      is smoked. Cigarettes have been designed to allow for a range of puffing behavior
      and to provide different, nonlinear tar and nicotine yields in response to
      different puffing profiles. However, puffing behavior and its influence upon risk
      exposure has yet to be assessed outside the laboratory, in smokers' natural
      environment. METHOD: Fifty-nine adult smokers used a portable device to measure
      smoking topography over the course of three 1-week trials. Participants were
      asked to smoke their usual "regular yield" brand through the device for trial 1
      and again, 6 weeks later, at trial 2. Half the subjects were then randomly
      assigned to switch to a "low-yield" brand for trial 3. RESULTS: The findings show
      a high degree of stability in puffing behavior within the same subject over time
      but considerable variability between smokers. Smokers who were switched to a "low
      yield" cigarette increased their total smoke intake per cigarette by 40% (P =
      0.007), with no significant change in their salivary cotinine levels. Cigarettes
      smoked per day and nicotine yield were only weakly associated with salivary
      cotinine levels; however, salivary cotinine was strongly associated with a
      composite measure that included cigarettes per day, brand elasticity, and puffing
      behavior (sr = 0.61, P < 0.001). CONCLUSIONS: These findings provide strong
      evidence of behavioral compensation to low-yield cigarettes from in vivo measures
      of smoking behavior. The findings also show the importance of brand elasticity
      and smoking topography in predicting nicotine uptake and smoke exposure.

PMID- 15941944
TI  - Carcinogen exposure during short-term switching from regular to "light"
      cigarettes.
AB  - OBJECTIVES: "Light" cigarettes are extremely popular and are perceived by many
      smokers as less hazardous than higher-yield cigarettes. The objectives of this
      study were (a) to assess a battery of biomarkers of tobacco smoke exposure that
      includes tobacco smoke carcinogens, (b) to examine the behavioral nature of
      compensation, and (c) to examine the consistency of an individual's tobacco smoke
      exposure when smoking the same cigarette at different times. METHODS: The study
      was a 3-week crossover study in which smokers smoked their usual cigarettes
      during weeks 1 and 3, and a light cigarette, with a machine-determined nicotine
      yield of about 50% of the usual cigarette, during week 2. Blood and urine
      biomarkers of exposure and subjective questionnaires were collected weekly.
      RESULTS: Based on cotinine and carboxyhemoglobin levels, compensation averaged
      78% and 83%, respectively. Urinary excretion of 4-(methylnitrosamino)-1-(3
      pyridyl)-butanol, a metabolite of the tobacco specific carcinogen 4
      (methylnitrosamino)-1-(3-pyridyl)-butanone, and a number of polycyclic aromatic
      hydrocarbon metabolites was similar in all conditions. Compensation was
      accomplished both by smoking cigarettes more intensively and by smoking more
      cigarettes per day. Exposures to various tobacco smoke constituents while smoking
      the usual brand of cigarette in weeks 1 and 3 were highly correlated. CONCLUSION:
      Our findings support the idea that smokers compensate to a high degree when
      switched from their usual brand to a light cigarette. Short-term switching
      resulted in no significant reduction in carcinogen exposure. Our assessment,
      based on measures of biochemical exposures, supports the idea that switching to
      light cigarettes is unlikely to reduce the health risks of cigarette smoking.

PMID- 15941945
TI  - Catechol-O-methyl-transferase functional polymorphism and nicotine dependence: an
      evaluation of nonreplicated results.
AB  - Review articles have focused attention on and cited possible reasons for the
      nonreplication of genetic association studies. Herein, we illustrate how one
      might work through these possible reasons to make a judgment about the most
      plausible reason(s) when faced with two or more studies which yield seemingly
      inconsistent results. In the first study, 342 treatment-seeking smokers were
      genotyped for the Val108Met polymorphism in the functional catechol-O-methyl
      transferase (COMT) locus. Alleles coding Val at codon 108 are denoted as H and
      those coding Met are denoted as L. An association between presence of the "H"
      (high activity) allele and pretreatment level of nicotine dependence level using
      the Fagerstrom Test for Nicotine Dependence was detected (P = 0.0072), after
      controlling for baseline body mass index (BMI, kg/m2), depression symptoms, and
      age. To validate this initial finding, 443 treatment-seeking smokers from an
      independent smoking cessation clinical trial were genotyped for the COMT
      polymorphism. Within the second study, no association between presence of the "H"
      allele and nicotine dependence was detected (P = 0.6418) after controlling for
      baseline BMI, depression symptoms, and age. We critically reviewed both studies
      with regard to often cited reasons for nonreplication, including type I error,
      population stratification, low statistical power, and imprecise measures of
      phenotype. Although in our opinion the failure to replicate the initial
      association in the second study is likely either the result of low statistical
      power to detect a small effect or effect heterogeneity, thorough analyses failed
      to definitively identify the reason for nonreplication.

PMID- 15941946
TI  - Family history of cancer, its combination with smoking and drinking, and risk of
      squamous cell carcinoma of the esophagus.
AB  - We analyzed the association between history of cancer in first-degree relatives
      and the risk of squamous cell carcinoma of the esophagus (SCCE) using data from
      three case-control studies conducted in Italy and Switzerland on 805 incident,
      histologically confirmed SCCE, and 3,461 hospital controls. The alcohol- and
      tobacco-adjusted odds ratio (OR) for a family history of esophageal cancer was
      3.2 [95% confidence interval (CI), 1.7-6.2], and the OR was higher when the
      affected relative was a brother or was diagnosed at age <55 years. Compared to
      subjects without family history of esophageal cancer, non-current smokers,
      drinking <49 drinks per week, the OR was 2.9 (95% CI, 1.1-7.5) for family history
      alone, 15.5 (95% CI, 11.7-20.5) for current smokers drinking > or = 49 drinks per
      week without family history of esophageal cancer, and 107.0 (95% CI, 13.0-880.2)
      for current smokers drinking > or = 49 drinks per week who also had a family
      history of esophageal cancer. The risk of SCCE was also increased in subjects
      with a family history of cancer of the oral cavity/pharynx (OR, 3.7; 95% CI, 1.5
      9.0) and stomach (OR, 2.0; 95% CI, 1.1-3.6), but not of other cancers, nor for a
      family history of any cancer (OR, 1.0; 95% CI, 0.8-1.4). These data show that, as
      for many other epithelial cancers, the risk of SCCE is increased in subjects with
      a family history of the disease, and that--in Western countries--avoidance of
      alcohol and tobacco is also the best way to prevent SCCE in subjects with a
      family history of the disease.

PMID- 15941947
TI  - Variation in plasma insulin-like growth factor-1 and insulin-like growth factor
      binding protein-3: genetic factors.
AB  - Insulin-like growth factors (IGFs) play key roles in cell proliferation and
      apoptosis. Whereas relatively stable within individuals, IGFs vary substantially
      between individuals, and a large component of this variation may be determined by
      genetic factors. Several polymorphisms in IGF genes have been identified,
      although their functional significance is not clear. We evaluated the association
      of polymorphisms in IGF-1 and IGFBP-3 and circulating levels of IGF-1 and IGFBP-3
      in 323 population-based control subjects enrolled in a case-control study of
      colorectal cancer from September 1999 through February 2002. Total IGF-1 and
      IGFBP-3 levels were measured using ELISA assays, and all subjects were genotyped
      for a microsatellite polymorphism in IGF-1 and a single nucleotide polymorphism
      in IGFBP-3. Multiple linear regression was used to assess the association of
      genotype with circulating IGFs. IGF-1 levels were unrelated to either
      polymorphism. IGFBP-3 was significantly associated with IGFBP-3 genotype, with
      IGFBP-3 levels increasing from CC (1,895 ng/mL) --> GC (2,029 ng/mL) --> GG
      (2,182 ng/mL), (p-trend < 0.001). Having an IGF-1 genotype other than homozygous
      for the 19-repeat allele was associated with higher IGFBP-3 levels (1,945 versus
      2,052 ng/mL). Furthermore, both IGF-1 and IGFBP-3 genotypes modified the
      relationship between postmenopausal hormone use and IGFs. This analysis provides
      evidence that common variation in IGF genes may contribute to the variation in
      circulating levels observed between individuals.

PMID- 15941948
TI  - Associations between plasma insulin-like growth factor proteins and C-peptide and
      quality of life in patients with metastatic colorectal cancer.
AB  - OBJECTIVE: Predictors of quality of life (QOL) in patients with metastatic
      colorectal cancer are lacking. The insulin-like growth factor (IGF) family of
      proteins is associated with QOL in noncancer populations. We sought to study
      whether these proteins are associated with QOL in patients with colorectal
      cancer. METHOD: We used a cohort of 526 patients with metastatic colorectal
      cancer treated with combination chemotherapy. Plasma samples of IGF-I, IGF-II,
      IGF binding protein-3, and C-peptide were collected before initiation of
      chemotherapy. QOL was measured by the uniscale instrument and the Symptom
      Distress Scale at baseline and throughout treatment. RESULTS: Baseline plasma
      levels of IGF-I and IGF-II before initiation of chemotherapy were significantly
      associated with several important baseline QOL measures in patients with
      metastatic colorectal cancer. Patients with lower levels of IGF-I reported
      increased distress with regard to appearance, appetite, cough, and nausea
      intensity after adjustment for potential confounders. Similarly, decreased levels
      of IGF-II were predictive of worse quality related to appearance, appetite,
      fatigue, nausea frequency and intensity, pain frequency, and composite Symptom
      Distress Scale score. IGF binding protein-3 and C-peptide were not predictive of
      baseline QOL. Baseline biomarkers were not associated with subsequent changes in
      QOL during treatment. Higher body mass index was significantly associated with
      superior baseline QOL in several areas; nonetheless, the association of IGF-I and
      IGF-II with baseline QOL measures remained significant even after controlling for
      baseline body mass index. CONCLUSION: Baseline plasma IGF-I and IGF-II are
      significantly associated with symptom distress. Whether this association is
      simply reflective of patient nutritional status and/or disease burden or
      represents an independent biological effect of IGFs on QOL remains uncertain.
      Nonetheless, these data suggest that molecular biomarkers may be useful
      predictors of QOL in cancer patients.

PMID- 15941949
TI  - Associations among circulating sex hormones, insulin-like growth factor, lipids,
      and mammographic density in postmenopausal women.
AB  - OBJECTIVE: Hormone therapy use has been positively associated with mammographic
      density in several studies. However, few studies have examined the association
      between endogenous hormone levels and mammographic density. Therefore, we
      evaluated the relationship of endogenous sex hormones, insulin-like growth factor
      (IGF), and lipids with mammographic density in 88 overweight, postmenopausal
      women not taking hormone therapy. METHODS: Percent density and dense area were
      evaluated as continuous measures using a computer-assisted program. We used
      multiple linear regression to evaluate the associations of sex hormones, IGF, and
      cholesterol with mammographic density, adjusting for confounders, including
      adiposity. We evaluated stratification by history of hormone therapy use (former
      versus never) and hormone therapy latency (<5 versus > or = 5 years). RESULTS:
      Among former hormone therapy users, mammographic density was inversely associated
      with circulating levels of estrone (P = 0.01), estradiol (P = 0.003), free
      estradiol (P = 0.004), testosterone (P = 0.04), free testosterone (P = 0.02),
      androstenedione (P < 0.001), dehydroepiandrosterone (P = 0.01), and the ratio of
      IGF-I to its binding protein (IGF-I/IGFBP-3; P = 0.04). We found similar
      associations when we limited the analyses to women who had used hormone therapy
      within the past 5 years. We also noted positive associations of mammographic
      density with total cholesterol (P = 0.03) and low-density lipoprotein (P = 0.03)
      among former hormone therapy users. No associations were noted among women who
      had never used hormone therapy. CONCLUSIONS: These results suggest that there is
      an inverse relationship between endogenous sex hormones and mammographic density
      in postmenopausal women among former users of hormone therapy. This is not
      consistent with the hormone therapy literature and should be confirmed in larger
      studies.

PMID- 15941950
TI  - Alpha-methylacyl-CoA racemase protein expression is associated with the degree of
      differentiation in breast cancer using quantitative image analysis.
AB  - Alpha-methylacyl-CoA racemase (AMACR) is an enzyme involved in the metabolism of
      fatty acids and is an important tissue biomarker in the prostate to distinguish
      normal glands from prostate cancer. Here, for the first time, we evaluated the
      expression of AMACR protein in normal breast, ductal carcinoma in situ, and
      invasive carcinomas. By immunofluorescence and immunohistochemistry, AMACR was
      seen in cytoplasmic granules consistent with a mitochondrial and peroxisomal
      localization. AMACR expression was determined by immunohistochemistry on 160
      invasive carcinomas with long follow-up, using a high-density tissue microarray,
      and evaluated by two methods: standard pathology review and quantitative image
      analysis. AMACR was overexpressed in 42 of 160 (26%) invasive carcinomas, and it
      was associated with a decrease in tumor differentiation, a feature of aggressive
      breast cancer. Quantitative analysis allowed for better discrimination and more
      accurate evaluation of low-intensity staining. In conclusion, AMACR protein is
      expressed in normal breast and its expression seems to increase in invasive
      carcinomas. We observed stronger AMACR protein expression in high-grade
      carcinomas when compared with low-grade ones. Quantitative image analysis is a
      novel way to accurately and reproducibly evaluate immunohistochemistry in breast
      tissue samples using high-density tissue microarrays.

PMID- 15941951
TI  - Decreased alpha-methylacyl CoA racemase expression in localized prostate cancer
      is associated with an increased rate of biochemical recurrence and cancer
      specific death.
AB  - Alpha-methylacyl CoA racemase (AMACR) is overexpressed in prostate cancer
      relative to benign prostatic tissue. AMACR expression is highest in localized
      prostate cancer and decreases in metastatic prostate cancer. Herein, we explored
      the use of AMACR as a biomarker for aggressive prostate cancer. AMACR protein
      expression was determined by immunohistochemistry using an image analysis system
      on two localized prostate cancer cohorts consisting of 204 men treated by radical
      prostatectomy and 188 men followed expectantly. The end points for the cohorts
      were time to prostate-specific antigen (PSA) failure (i.e., elevation >0.2 ng/mL)
      and time to prostate cancer death in the watchful waiting cohort. Using a
      regression tree method, optimal AMACR protein expression cut-points were
      determined to best differentiate prostate cancer outcome in each of the cohorts
      separately. Cox proportional hazard models were then employed to examine the
      effect of the AMACR cut-point on prostate cancer outcome, and adjusted for
      clinical variables. Lower AMACR tissue expression was associated with worse
      prostate cancer outcome, independent of clinical variables (hazard ratio, 3.7 for
      PSA failure; P = 0.018; hazard ratio, 4.1 for prostate cancer death, P = 0.0006).
      Among those with both low AMACR expression and high Gleason score, the risk of
      prostate cancer death was 18-fold higher (P = 0.006). The AMACR cut-point
      developed using prostate cancer-specific death as the end point predicted PSA
      failures independent of Gleason score, PSA, and margin status. This is the first
      study to show that AMACR expression is significantly associated with prostate
      cancer progression and suggests that not all surrogate end points may be optimal
      to define biomarkers of aggressive prostate cancer.

PMID- 15941952
TI  - Fruit and vegetable intake during pregnancy and risk for development of sporadic
      retinoblastoma.
AB  - OBJECTIVE: Little is known about the causes of sporadic (noninherited)
      retinoblastoma. Rates seem to be somewhat higher among poorer populations in
      Mexico. Fruits and vegetables are important sources of carotenoids and folate. We
      examined whether decreased gestational maternal intake of fruits and vegetables
      may contribute to development of sporadic retinoblastoma. METHODS: At the
      Instituto Nacional de Pediatria in Mexico City, we conducted a hospital-based
      case-control study to evaluate prenatal maternal diet. We examined dietary intake
      of fruits and vegetables of mothers of 101 children with retinoblastoma and 172
      control children using a dietary recall questionnaire and published food nutrient
      content tables. RESULTS: The reported number of mean daily servings of fruits and
      vegetables was lower among case mothers when compared with control mothers
      [vegetables: 2.28 in controls, 1.75 in cases (P < 0.01); fruits: 2.13 in
      controls, 1.59 in cases (P = 0.07)]. Mean daily maternal folate intake from both
      vegetables and fruits was higher in controls (103 microg) than in cases (48
      microg; P < 0.05). Risk for having a child with retinoblastoma was increased for
      mothers consuming fewer than 2 daily servings of vegetables [odds ratios (OR),
      3.4; 95% confidence interval (95% CI), 2.0-6.0] or with a low intake of folate
      (OR, 3.9; 95% CI, 2.1, 7.3), or lutein/zeaxanthin (OR, 2.6; 95% CI, 1.5-4.6)
      derived from fruits and vegetables. CONCLUSIONS: Decreased intake of vegetables
      and fruits during pregnancy and the consequent decreased intake of nutrients such
      as folate and lutein/zeaxanthin, necessary for DNA methylation, synthesis, and
      retinal function, may increase risk for having a child with sporadic
      retinoblastoma.

PMID- 15941953
TI  - Neighborhood socioeconomic status and Hodgkin's lymphoma incidence in California.
AB  - Hodgkin's lymphoma occurrence has long been noted to associate with higher
      socioeconomic status (SES). However, the Hodgkin's lymphoma-SES association has
      not been examined recently or across important, possibly etiologically distinct,
      patient subgroups. In approximately 150 million person-years of observation in
      the multiethnic population of California, we examined the association of
      Hodgkin's lymphoma incidence with a composite measure of neighborhood-level SES
      in patient subgroups defined by age, sex, race/ethnicity, and Hodgkin's lymphoma
      histologic subtype. Using population-based cancer registry data on 3,794
      Hodgkin's lymphoma patients diagnosed 1988 to 1992 and 1990 census data, we
      assigned a previously validated, multidimensional SES index to census block
      groups of patient residence. We then calculated neighborhood SES-specific
      incidence rates and estimated rate ratios using Poisson regression. Positive
      neighborhood SES gradients in Hodgkin's lymphoma incidence were observed only in
      young adults (ages 15-44 years at diagnosis) with nodular sclerosis Hodgkin's
      lymphoma and older adult (ages > or =45 years) White and Hispanic males with
      mixed cellularity Hodgkin's lymphoma. For young adults, associations were marked
      in Hispanic and Asian women, weaker in Hispanic and White men and White women,
      and subtle to nonexistent in Blacks and Asian men. Neighborhood SES gradients in
      Hodgkin's lymphoma incidence varied by age, sex, race/ethnicity, and histologic
      subtype, underscoring etiologic complexity in Hodgkin's lymphoma. Racial/ethnic
      gradients were not entirely explained by neighborhood SES. In California,
      etiologically relevant exposures for young adult Hodgkin's lymphoma, the most
      common form, could associate more with race/ethnicity or foreign birthplace than
      neighborhood SES and may be modified by reproductive or other sex-specific
      factors.

PMID- 15941954
TI  - Markers of past infection with simian virus 40 (SV40) and risk of incident non
      Hodgkin lymphoma in a Maryland cohort.
AB  - Simian virus 40 (SV40) genome sequences have been detected in human non-Hodgkin
      lymphoma (NHL) tissues, and past infection with SV40 may be a risk factor for
      NHL. We conducted a population-based nested case-control study to investigate the
      association between serum antibodies to SV40 and incident NHL. Two research serum
      banks were established in Washington County, MD, with >45,000 volunteers
      contributing blood samples collected in 1974 and 1989. Incident cases of NHL
      diagnosed through 2002 (n = 170) were identified among participants by linkage to
      population-based cancer registries. Two controls were matched to each case (n =
      340) on age, sex, and date of blood draw. Circulating immunoglobulin G antibodies
      to SV40 were measured using virus-like particle (VLP) ELISA. Positive samples
      were tested for cross-reactivity with JC virus (JCV) and BK virus (BKV) through
      competitive inhibition assays. Associations between SV40 antibody seropositivity
      and NHL were estimated using conditional logistic regression. Whereas SV40
      antibodies were detected by VLP ELISA in 15% of cases and 10% of controls
      [matched odds ratio (OR), 1.97; 95% confidence interval (95% CI), 1.03-3.76], the
      SV40 reactivity of 85% of the SV40 antibody-positive sera was decreased by
      adsorption with BKV and/or JCV VLPs. Antibodies specific for SV40 (not cross
      reactive) were identified in only 1.8% of cases and 1.6% of controls (OR, 1.51;
      95% CI, 0.41-5.52). Our findings suggest that past infection with SV40 is not
      associated with an increased risk of developing NHL.

PMID- 15941955
TI  - Project PREVENT: a randomized trial to reduce multiple behavioral risk factors
      for colon cancer.
AB  - BACKGROUND: This report examines the outcome data for Project PREVENT, a two-site
      randomized control trial designed to reduce behavioral risk factors for
      colorectal cancer among individuals who have been diagnosed with adenomatous
      colon polyps. METHODS: The study sample included 1,247 patients with recent
      diagnosis of adenomatous colorectal polyps. Within 4 weeks following the
      polypectomy, participants completed a baseline survey by telephone, and were
      randomized to either Usual Care (UC) or the PREVENT intervention, which was
      designed to target multiple risk factors. The intervention consisted of a
      telephone-delivered intervention plus tailored materials, and focused on the six
      primary behavioral risk factors for colorectal cancer, including red meat
      consumption, fruit and vegetable intake, multivitamin intake, alcohol, smoking,
      and physical inactivity. RESULTS: Participation in the PREVENT intervention was
      associated with a significantly greater reduction in prevalence of multiple risk
      factors for colorectal cancer compared with UC. Only about one third of UC
      participants dropped any risk factors during the study period, compared with
      almost half of the PREVENT participants. PREVENT participants were also
      significantly more likely to change more than one behavior than UC participants.
      CONCLUSIONS: The PREVENT intervention was effective in helping patients change
      multiple risk factors. These results provide further support that more
      comprehensive interventions that move beyond emphasis on a single risk factor are
      acceptable to patient populations, can result in improvements, and are cost
      effective.

PMID- 15941956
TI  - Evidence for an association between compound heterozygosity for germ line
      mutations in the hemochromatosis (HFE) gene and increased risk of colorectal
      cancer.
AB  - Whereas a recent study reported an increased risk of colorectal cancer associated
      with any HFE germ line mutation (C282Y or H63D), other investigators have
      concluded there is no increased risk, or that any increase is dependent on
      polymorphisms in HFE-interacting genes such as the transferrin receptor (TFR). We
      have established the frequency of HFE mutations in colorectal cancer patients (n
      = 327) with a family history of the disease and randomly selected controls (n =
      322); this design increases greatly the study's power. Genotyping for the TRF
      S142G polymorphism was also conducted on a large proportion of the study group.
      Using PCR, restriction enzyme mapping, sequencing followed by data analysis with
      Fisher's exact test and logistic regression, we show that the presence of any HFE
      mutation (Y282 or D63) was not associated with colorectal cancer risk (P = 0.57).
      In contrast, individuals compound heterozygous for both mutations (15 cases
      versus 5 controls) had thrice the odds of developing colorectal cancer (odds
      ratio, 3.03; 95% confidence interval, 1.06-8.61) compared with those with a
      single mutation. This finding did not quite reach statistical significance after
      allowing for multiple post hoc testing (P(observed) = 0.038 versus P = 0.025,
      with Bonferonni correction). Overall, our data indicate that individuals with a
      single HFE mutation, C282Y or H63D, are unlikely predisposed to develop
      colorectal cancer. However, risk of colorectal cancer might be increased by
      compound heterozygosity for the HFE mutations in the small number of subjects
      studied. TFR gene polymorphism was not an independent risk factor and did not
      modify the disease risk associated with HFE mutation.

PMID- 15941957
TI  - Intestinal helminthiasis in Colombian children promotes a Th2 response to
      Helicobacter pylori: possible implications for gastric carcinogenesis.
AB  - BACKGROUND: Colombians living in coastal Tumaco have a lower incidence of
      Helicobacter pylori-associated gastric cancer compared with residents of Pasto in
      the high Andes. Considering the risk for H. pylori disease seems affected by
      features of bacterial virulence and host polymorphisms, other poorly understood
      influences, such as concurrent helminthiasis, may also be important. METHODS:
      Fecal samples from 211 children were tested for parasites and sera from another
      cohort of 159 children and 92 adults were tested for IgE and H. pylori-specific
      IgG. RESULTS: Most individuals (95%) from both areas were H. pylori seropositive,
      with a predominant response of IgG1 followed by IgG2 and low IgG3 and IgG4
      antibodies. Compared with Pasto children, Tumaco children were more commonly
      infected with helminths (P = 0.000), had higher serum IgE levels (P < 0.03), and
      had higher Th2-associated IgG1 responses to H. pylori (P < 0.0002). Other IgG
      isotype responses all increased with age but were not significantly different
      between children and adults from either area. CONCLUSIONS: These results suggest
      that intestinal helminthiasis in children promotes Th2-polarizing responses to H.
      pylori and may decrease gastric cancer risk in these individuals later in life.
      Concurrent helminthiasis may alter inflammatory responses to H. pylori and thus
      affect the progression of gastritis to gastric atrophy, dysplasia, and cancer.

PMID- 15941958
TI  - 5,10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic
      cancer.
AB  - To test the hypothesis that 5,10-methylenetetrahydrofolate reductase (MTHFR)
      polymorphisms modify the risk of pancreatic cancer, we conducted a hospital
      based, case-control study involving 347 patients with newly diagnosed pancreatic
      adenocarcinoma and 348 healthy controls, frequency matched by age, sex, and race.
      MTHFR polymorphisms were determined using the PCR-RFLP method. Association of
      these polymorphisms with the risk of pancreatic cancer was estimated by
      unconditional logistic regression analysis. We found that the C667T (but not the
      A1298C) polymorphism had a significant main effect on the risk of pancreatic
      cancer. The frequencies of the MTHFR 667CC, 667CT, and 667TT genotypes were
      49.5%, 38.6%, and 11.9%, respectively, among cases compared with 48.5%, 45.0%,
      and 6.5%, respectively, among controls. Individuals with the 667TT genotype
      displayed a 2-fold increased risk for pancreatic cancer compared with those with
      the CC/CT genotypes [adjusted odds ratio (OR), 2.14; 95% confidence interval (95%
      CI), 1.14-4.01]. Multivariate analyses found that the effect of the 677TT
      genotype on the risk of pancreatic cancer was present among ever smokers (OR,
      5.53; 95% CI, 2.0-15.3) and ever alcohol drinkers (OR, 3.16; 95% CI, 1.30-7.69)
      but not in never smokers (OR, 0.82; 95% CI, 0.33-2.06) and never drinkers (OR,
      1.42; 95% CI, 0.56-3.62). Furthermore, a positive interaction between the MTHFR
      TT genotype and heavy smoking or heavy alcohol consumption was detected. The OR
      (95% CI) of pancreatic cancer was 6.83 (1.91-24.38) for heavy smokers among the
      TT carriers compared with never smokers with the CC/CT genotypes and 4.23 (0.88
      20.3) for heavy drinkers with the TT genotype compared with nondrinkers with the
      CC/CT genotypes. These observations support a role for folate metabolism in
      pancreatic cancer, especially among smokers and heavy drinkers.

PMID- 15941959
TI  - Sex differences in risk of lung cancer associated with methylene-tetrahydrofolate
      reductase polymorphisms.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyzes the metabolism of folate
      and nucleotides needed for DNA synthesis and repair. Variations in MTHFR
      functions likely play roles in the etiology of lung cancer. The MTHFR gene has
      three nonsynonymous single nucleotide polymorphisms (i.e., C677T, A1298C, and
      G1793A) that have a minor allele frequency of >5%. We investigated the
      associations between the frequencies of MTHFR variant genotypes and risk of lung
      cancer in a hospital-based case-control study of 1,051 lung cancer patients and
      1,141 cancer-free controls in a non-Hispanic White population. We found that
      compared with the MTHFR 1298AA genotype, the 1298CC genotype was associated with
      a significantly increased risk of lung cancer in women [(odds ratio (OR), 2.09;
      95% confidence interval (95% CI), 1.32-3.29)] but not in men (OR, 0.95; 95% CI,
      0.62-1.45). The MTHFR 677TT genotype was associated with a significantly
      decreased risk of lung cancer in women (OR, 0.60; 95% CI, 0.40-0.92) but not in
      men. No association was found between the MTHFR G1793A polymorphism and risk of
      lung cancer. Further analysis suggested evidence of gene-dietary interactions
      between the MTHFR C677T polymorphism and dietary intake of vitamin B6, vitamin
      B12, and methionine in women and evidence of gene-environment interactions
      between the MTHFR C677T and A1298C polymorphisms and tobacco smoking in men. In
      conclusion, the polymorphisms of MTHFR may contribute to the risk of lung cancer
      in non-Hispanic Whites and modify the risk associated with the dietary and
      environmental exposure in a sex-specific manner.

PMID- 15941960
TI  - Behavioral consequences of testing for obesity risk.
AB  - OBJECTIVE: There is considerable hope that genetic susceptibility testing will
      motivate behavior that can prevent or reduce the risk of complex conditions such
      as obesity. This study examined potential behavioral consequences of such
      testing. METHODS: Participants (n = 249) were randomly assigned to review one of
      four vignettes that asked them to imagine that they had been tested for their
      risk of becoming overweight or obese. The experimental factors were test type
      (genetic versus hormone test) and risk level (increased versus average risk for
      obesity). Study measures included behavioral intentions and perceived behavioral
      control related to eating a healthy diet, as well as weight locus of control.
      RESULTS: Participants assigned to the increased risk conditions indicated greater
      intentions to eat a healthy diet compared with participants assigned to the
      average risk conditions (P < 0.02). There were significant interaction effects of
      risk x perceived behavioral control (P < 0.02) and risk x weight locus of control
      (P < 0.003) on dietary intentions. Individuals with low perceived behavioral
      control or an external weight locus of control who were told to imagine they were
      at average risk expressed significantly lower intentions to eat a healthy diet. A
      three-way interaction of body mass index, family history of overweight/obesity,
      and assigned risk level found the greatest effects of risk feedback among those
      who either had a family history or a higher body mass index (P < 0.007).
      CONCLUSION: This study provides preliminary evidence that testing for
      susceptibility to obesity may motivate healthier behavior. However, some
      individuals may be susceptible to a false reassurance effect after receiving test
      results indicating a lack of increased risk.

PMID- 15941961
TI  - Physical activity and the risk of prostate cancer in the Netherlands cohort
      study, results after 9.3 years of follow-up.
AB  - BACKGROUND: The aim of the current study was to evaluate the relation between
      physical activity and prostate cancer risk with specific emphasis on interaction
      with body mass index (BMI) and baseline energy intake. METHODS: The association
      between prostate cancer and physical activity was evaluated in the Netherlands
      Cohort Study, conducted among 58,279 men ages 55 to 69 years at entry.
      Information regarding baseline nonoccupational physical activity, history of
      sports participation, and occupational physical activity was collected with a
      questionnaire in 1986. After 9.3 years, 1,386 incident prostate cancer cases were
      available for case-cohort analyses. Multivariate incidence rate ratios (RR) and
      corresponding 95% confidence intervals (95% CI) were calculated using Cox
      regression analyses. RESULTS: Neither baseline nonoccupational physical activity
      (RR, 1.01; 95% CI, 0.81-1.25 for >90 versus <30 minutes per day), history of
      sports participation (RR, 1.04; 95% CI, 0.90-1.22 for ever versus never
      participated), nor occupational physical activity (RR, 0.91; 95% CI, 0.70-1.18
      for >12 versus <8 KJ/min energy expenditure in the longest held job) showed an
      inverse relation with prostate cancer risk. We found an increased risk of
      prostate cancer for men who were physically active for >1 hour per day in obese
      men (BMI > 30) and men with a high baseline energy intake. DISCUSSION: The
      results of this current study do not support the hypothesis that physical
      activity protects against prostate cancer in men.

PMID- 15941962
TI  - Energy balance and breast cancer risk.
AB  - We evaluated the hypothesis that a pattern of behavioral exposures indicating
      positive energy balance [i.e., less exercise/sport activity, high body mass index
      (BMI), or high energy intake] would be associated with an increased breast cancer
      risk in the Shanghai Breast Cancer Study, a population-based study of 1,459
      incident breast cancer cases and 1,556 age frequency-matched controls.
      Participants completed in-person interviews that collected information on breast
      cancer risk factors, usual dietary intake and physical activity in adulthood.
      Anthropometric indices were measured. Odds ratios and 95% confidence intervals
      were estimated by logistic regression to describe the individual and joint
      effects of the exposures on breast cancer risk. Lack of exercise/sport activity,
      low occupational activity, and high BMI were all individually associated with
      increased risk of breast cancer [odds ratios (OR) ranged from 1.49 to 1.86]. In
      general, women with lower exercise/sport activity level and higher BMI, or those
      with higher energy intake, were at an increased risk compared with women who
      reported more exercise/sport activities, had lower BMIs, or reported less energy
      intake. There was a significant multiplicative interaction (P = 0.02) between
      adult exercise/sport activity and BMI, with inactive women in the upper BMI
      quartile being at increased risk (OR, 2.16; 95% confidence interval, 1.25-3.74)
      compared with their active and lean counterparts. This association was stronger
      in postmenopausal than in premenopausal women, and non-exercising postmenopausal
      women with higher BMIs were at substantially increased risk (OR, 4.74; 95%
      confidence interval, 2.05-12.20). Our study suggests that promotion of behavior
      patterns that optimize energy balance (weight control and increasing physical
      activity) may be a viable option for breast cancer prevention.

PMID- 15941963
TI  - Prenatal and perinatal correlates of adult mammographic breast density.
AB  - BACKGROUND: Adult mammographic percent density is one of the strongest known risk
      factors for breast cancer. In utero exposure to high levels of endogenous
      estrogens (or other pregnancy hormones) has been hypothesized to increase breast
      cancer risk in later life. We examined the hypothesis that those factors
      associated with higher levels of estrogen during pregnancy or shortly after birth
      are associated with higher mammographic breast density in adulthood. METHODS: We
      analyzed data on 1,893 women from 360 families in the Minnesota Breast Cancer
      Family Study who had screening mammograms, risk factor data, over age 40, and no
      history of breast cancer. Prenatal and perinatal risk factor data were
      ascertained using a mailed questionnaire. Mammographic percent density and dense
      area were estimated from the mediolateral oblique view using Cumulus, a computer
      assisted thresholding program. Linear mixed effects models incorporating familial
      correlation were used to assess the association of risk factors with percent
      density, adjusting for age, weight, and other breast cancer risk factors, all at
      time of mammography. RESULTS: The mean age at mammography was 60.4 years (range,
      40-91 years), and 76% were postmenopausal. Among postmenopausal women, there was
      a positive association of birthweight with percent density (P trend <0.01), with
      an adjusted mean percent density of 17.1% for <2.95 kg versus 21.0% for > or =
      3.75 kg. There were suggestive positive associations with gestational age (mean
      percent density of 16.7% for preterm birth, 20.2% for term birth, and 23.0% for
      late birth; P trend = 0.07), maternal eclampsia/preeclampsia (mean percent
      density of 19.9% for no and 14.6% for yes; P = 0.16), and being breast-fed as an
      infant (mean percent density of 18.2% for never and 20.0% for ever; P = 0.08).
      There was no association of percent density with maternal age, birth order,
      maternal use of alcohol or cigarettes, or neonatal jaundice. Except for being
      breast-fed, these associations showed similar but attenuated trends among
      premenopausal women, although none were statistically significant. The results
      for dense area paralleled the percent density results. The associations of
      gestational age and being breast-fed as an infant with percent density attenuated
      when included in the same model as birthweight. CONCLUSIONS: Birthweight was
      positively associated with mammographic breast density and dense area among
      postmenopausal women and more weakly among premenopausal women, suggesting that
      it may be a marker of this early life exposure. These results offer some support
      to the hypothesis that pregnancy estrogens or other pregnancy changes may play a
      role in breast cancer etiology, and suggest that these factors may act in part
      through long-term effects on breast density.

PMID- 15941964
TI  - Menstrual cycle characteristics and incidence of premenopausal breast cancer.
AB  - BACKGROUND: Epidemiologic studies have indicated that menstrual cycle
      characteristics such as age at menarche and age at menopause are associated with
      breast cancer risk. Anovulation, which is more common with long or irregular
      cycles, has been hypothesized to reduce the incidence of breast cancer. METHODS:
      We analyzed data from the Nurses' Health Study II, a cohort of 116,671 female
      registered nurses ages 25 to 42 years at baseline. Information on menstrual cycle
      characteristics was assessed in 1989 and 1993, and incident cases of
      premenopausal breast cancer were ascertained through 2001. RESULTS: During
      1,135,496 person-years of follow-up (1989-2001), 1,163 incident cases of invasive
      premenopausal breast cancer were diagnosed. Overall, women with long menstrual
      cycles at ages 18 to 22 years (>32 days or too irregular to estimate) did not
      experience a significantly lower breast cancer risk compared with women with
      normal cycle lengths (26-31 days) at that age [covariate-adjusted hazard ratio
      (HR), 0.92; 95% confidence interval (95% CI), 0.79-1.06]. Among women ages <40
      years, those with menstrual cycles lasting >32 days or too irregular to estimate
      at ages 18 to 22 years had a decreased incidence of breast cancer (covariate
      adjusted HR, 0.71; 95% CI, 0.53-0.97). Current menstrual cycle characteristics
      were not associated with breast cancer incidence. CONCLUSION: Overall, longer or
      irregular cycles at ages 18 to 22 years or in early adulthood were not associated
      with reduced premenopausal breast cancer risk. However, longer menstrual cycles
      at ages 18 to 22 years were associated with a lower incidence of premenopausal
      breast cancer before age 40.

PMID- 15941965
TI  - Pregnancy hormone concentrations across ethnic groups: implications for later
      cancer risk.
AB  - A variety of in utero factors have been associated with risk of adult cancers,
      particularly birth weight, toxemia, and gestational age. These factors are
      thought to reflect hormonal exposures during pregnancy. We hypothesized that the
      prenatal hormonal milieu may explain part of the variation in cancer rates across
      ethnic groups, for example, the higher incidence of breast cancer in the
      Caucasian compared with Hispanic women and the higher incidence of prostate and
      lower incidence of testicular cancers among African-Americans compared with
      Caucasians. We measured hormones in early pregnancy blood samples from three
      ethnic groups in a health care plan in Boston, MA. Mean levels of
      androstenedione, testosterone, estrone, and prolactin were significantly lower in
      Caucasian women compared with Hispanic women. Although not statistically
      significant, estradiol levels were lower in Caucasian compared with Hispanic or
      African-American women. Concentrations of androstenedione, testosterone, and
      progesterone were notably higher in African-American compared with Caucasian or
      Hispanic women. These data are consistent with hypotheses that in utero hormonal
      exposures may explain some of the ethnic group differences in cancer risk.

PMID- 15941966
TI  - Association of genetic polymorphisms with serum estrogens measured multiple times
      during a 2-year period in premenopausal women.
AB  - There is evidence that circulating estrogens are associated with breast cancer
      risk. In this study of premenopausal women, we explored the association of
      polymorphisms in genes in the estrogen synthesis and metabolism pathways with
      serum and urinary levels of estrone (E1) and estradiol (E2) and with the urinary
      ratio of 2-hydroxyestrone (2-OHE1)/16alpha-hydroxyestrone (16alpha-OHE1). This
      analysis included 220 women, who were participants in a 2-year randomized soy
      intervention. Blood specimens were collected in the luteal phase of the menstrual
      cycle an average of 4.4 times over 2 years. Overnight urinary specimens were
      collected on the same cycle day, only at baseline. Levels of E1, E2, 2-OHE1, and
      16alpha-OHE1 were measured by enzyme immunoassays. The DNA samples were analyzed
      by PCR/RFLP for the COMT Val158Met, CYP1A1*2A, CYP1A1*2B, CYP1A2*1F, CYP1B1
      Val432Leu, and CYP17 T27C polymorphisms. We applied mixed models to investigate
      the relations between genotypes and repeated serum hormone measurements and
      generalized linear models to assess associations between genotypes and urinary
      estrogen metabolites. The CYP1A2 C allele was significantly associated with lower
      serum E2 levels; in CC genotype carriers, serum E2 levels were 26.3% lower than
      in homo- and heterozygous common allele carriers combined (P = 0.01). CYP1A2*1F
      also affected the urinary 2-OHE1/16alpha-OHE1 ratio; carriers of the variant C
      allele had a markedly lower ratio than individuals with the AA genotype (1.37
      versus 1.76; P = 0.002). These data suggest that CYP1A2*1F is associated with
      lower circulating levels of E2, and that it may be a susceptibility locus for
      breast cancer.

PMID- 15941967
TI  - Acquisition and persistence of human papillomavirus infection in younger men: a
      prospective follow-up study among Danish soldiers.
AB  - No data is yet available on incidence or persistence of human papillomavirus
      (HPV) infection in men. We enrolled 374 younger male conscripts (18-29 years) in
      a prospective study, and they were examined twice with an interval of 6 to 8
      months. Data collection included a questionnaire and a sample of cells from the
      penis for HPV detection using PCR. In addition, the presence of Chlamydia
      trachomatis DNA was assessed in urine samples by means of PCR. The HPV prevalence
      at the first and second examinations was 33.8% and 31.9%, respectively. The
      acquisition rate of HPV (overall) during follow-up was 13.8%, and nearly one
      fourth of the participants were HPV positive at both examinations. Number of sex
      partners during follow-up was the most important risk factor for acquiring HPV
      (odds ratio, 17.2; 95% confidence interval, 4.6-64.7, for > or = 3 partners
      versus < or = 1 partner). In contrast, acquisition of a new HPV type in initially
      HPV-positive men was strongly related to having multiple HPV types at enrollment
      (OR, 4.1; 95% confidence interval, 1.4-12.3). This was also the most important
      risk factor for HPV persistence together with current smoking and having a high
      risk HPV type at enrollment. This is the first study to assess risk factors for
      acquisition and persistence of HPV. The sexually transmitted nature of the
      infection is confirmed, and the data point to an important role of having
      multiple HPV types for persistence.

PMID- 15941968
TI  - A comparison of bilateral breast cancers in BRCA carriers.
AB  - BACKGROUND: Women with breast cancer and a BRCA mutation have a high risk of
      developing a contralateral breast cancer. It is generally believed that the two
      cancers represent independent events. However, the extent of concordance between
      the first and second tumors with respect to hormone receptor expression and other
      pathologic features is unknown. PURPOSE: To determine the degree of concordance
      of estrogen receptor (ER) status, tumor grade, and histology in tumors from women
      with bilateral breast cancer and a BRCA mutation. SUBJECTS AND METHODS: Women
      with a history of bilateral invasive breast cancers were selected from an
      international registry of women with BRCA1 or BRCA2 mutations. Medical records
      were reviewed to document the characteristics of each cancer and the treatments
      received. RESULTS: Data were available for 286 women with bilateral breast cancer
      and a BRCA mutation (211 BRCA1; 75 BRCA2). The mean interval between first and
      second tumor was 5.1 years. The two tumors were concordant more often than
      expected for ER status (P < 0.0001) and for grade (P < 0.0001), but not for
      histology (P = 0.55). The ER status of the first tumor was highly predictive of
      the ER status of the second tumor (odds ratio, 8.7; 95% confidence interval, 3.5
      21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use
      was predictive of the ER status of the second tumor. CONCLUSIONS: There is strong
      concordance in ER status and tumor grade between independent primary breast
      tumors in women with a BRCA mutation. The excess concordance may be due to common
      risk factors, genetic variation, or the existence of a preneoplastic lesion that
      is common to both tumors.

PMID- 15941969
TI  - Genetic variation in XPD, sun exposure, and risk of skin cancer.
AB  - The XPD gene is involved in the nucleotide excision repair pathway removing DNA
      photoproducts induced by UV radiation. Genetic variation in XPD may exert a
      subtle effect on DNA repair capacity. We assessed the associations between two
      common nonsynonymous polymorphisms (Asp312Asn and Lys751Gln) with skin cancer
      risk in a nested case-control study within the Nurses' Health Study (219
      melanoma, 286 squamous cell carcinoma, 300 basal cell carcinoma, and 874
      controls) along with exploratory analysis on the haplotype structure of the XPD
      gene. There were inverse associations between the Lys751Gln and Asp312Asn
      polymorphisms and the risks of melanoma and squamous cell carcinoma. No
      association was observed between these two polymorphisms and basal cell carcinoma
      risk. We also observed that the association of the 751Gln allele with melanoma
      risk was modified by lifetime severe sunburns, cumulative sun exposure with a
      bathing suit, and constitutional susceptibility score (P for interaction = 0.03,
      0.04, and 0.02 respectively). Similar interactions were also observed for the
      Asp312Asn. Our data suggest these two XPD nonsynonymous polymorphisms may be
      associated with skin cancer risk, especially for melanoma.

PMID- 15941970
TI  - Examining population stratification via individual ancestry estimates versus self
      reported race.
AB  - Population stratification has the potential to affect the results of genetic
      marker studies. Estimating individual ancestry provides a continuous measure to
      assess population structure in case-control studies of complex disease, instead
      of using self-reported racial groups. We estimate individual ancestry using the
      Federal Bureau of Investigation CODIS Core short tandem repeat set of 13 loci
      using two different analysis methods in a case-control study of early-onset lung
      cancer. Individual ancestry proportions were estimated for "European" and "West
      African" groups using published allele frequencies. The majority of Caucasian,
      non-Hispanics had >50% European ancestry, whereas the majority of African
      Americans had <20% European ancestry, regardless of ancestry estimation method,
      although significant overlap by self-reported race and ancestry also existed.
      When we further investigated the effect of ancestry and self-reported race on the
      frequency of a lung cancer risk genotype, we found that the frequency of the
      GSTM1 null genotype varies by individual European ancestry and case-control
      status within self-reported race (particularly for African Americans). Genetic
      risk models showed that adjusting for individual European ancestry provided a
      better fit to the data compared with the model with no group adjustment or
      adjustment for self-reported race. This study suggests that significant
      population substructure differences exist that self-reported race alone does not
      capture and that individual ancestry may be confounded with disease status and/or
      a candidate gene risk genotype.

PMID- 15941971
TI  - Is the association with fiber from foods in colorectal cancer confounded by
      folate intake?
AB  - The effect of multivariate adjustment including folate on the strong protective
      effect of fiber in foods on colorectal cancer risk in the European Prospective
      Investigation into Cancer and Nutrition was investigated in 1,721 cases
      identified in the latest follow-up. The inclusion of an additional 656 cases
      confirmed our previously published results, with a strong and significant
      reduction in colorectal cancer risk of approximately 9% for each uncalibrated
      quintile increase in fiber (P(linear trend) < 0.001) compared with an 8%
      reduction in our previous report, which had not been adjusted for folate.
      Inclusion of the other covariates (physical activity, alcohol, smoking, and red
      and processed meat) confirmed this significant inverse association for colon
      cancer and strengthened the association with left-sided colon cancer (P < 0.001).
      After maximum adjustment, the association between fiber and rectal cancer was not
      significant, as in our previous analysis. The association with fiber from
      different food sources was analyzed, but again, there were no significance trends
      after maximum adjustment.

PMID- 15941972
TI  - Prediagnostic plasma vascular endothelial growth factor levels and risk of
      prostate cancer.
AB  - Vascular endothelial growth factor (VEGF) plays important roles in endothelial
      cell proliferation, vascular permeability, and angiogenesis that may be critical
      to prostatic carcinogenesis and progression. Plasma VEGF levels were
      significantly greater in patients with metastatic prostate cancer compared with
      those with localized disease or healthy controls, and plasma VEGF level at
      prostate cancer diagnosis was an independent prognostic marker for survival in
      patients with hormone refractory prostate cancer. We therefore examined the
      association between prediagnostic plasma VEGF levels and risk of prostate cancer
      and disease phenotype. Using plasma samples obtained in 1982 from healthy men
      enrolled in the Physicians' Health Study, we conducted a nested case-control
      study among 504 men diagnosed with prostate cancer during 13 years of follow-up
      and 520 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were
      calculated using multivariate logistic regression. Prediagnostic plasma VEGF
      levels were similar among cases and controls. Plasma VEGF concentration was not
      associated with subsequent risk of prostate cancer (third versus first tertile
      OR, 1.09; 95% CI, 0.80-1.49; P(trend) = 0.65). Furthermore, no association was
      observed among men with advanced (stage C or D) prostate cancer or among those
      who died of prostate cancer. Our results indicate that prediagnostic circulating
      VEGF levels are not associated with prostate cancer development and have limited
      value in predicting future risk of prostate cancer.

PMID- 15941973
TI  - Dietary intake of folate and riboflavin, MTHFR C677T genotype, and colorectal
      adenoma risk: a Dutch case-control study.
AB  - We investigated the associations between dietary intake of folate and vitamin B2,
      MTHFR C677T genotype, and colorectal adenomas in a Dutch case-control study. Data
      of cases with at least one histologically confirmed colorectal adenoma (n = 768)
      and controls with no history of any type of colorectal polyp (n = 709) were
      included. Dietary intake was assessed using a food-frequency questionnaire.
      Multivariable models included age and, if appropriate, dietary folate and calcium
      intake. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the
      highest compared with the lowest sex-specific tertile of intake were 1.32 (95%
      CI, 1.01-1.73) for folate and 0.51 (95% CI, 0.36-0.73) for vitamin B2. Folate
      seemed to be a risk factor, especially when vitamin B2 intake was low; vitamin B2
      was inversely associated with adenomas, especially with relatively high folate
      intake. No association was observed between MTHFR C677T genotype and colorectal
      adenomas. The inverse association between vitamin B2 intake and colorectal
      adenoma risk seemed to be more pronounced among those with the MTHFR TT genotype.
      We conclude that this study does not provide evidence for a decreased colorectal
      adenoma risk for subjects with high dietary intake of folate. It suggests,
      however, an inverse association between vitamin B2 and colorectal adenomas, which
      may be more relevant for those with the MTHFR TT genotype.

PMID- 15941974
TI  - Genetic polymorphisms of the transforming growth factor-beta1 gene and breast
      cancer risk: a possible dual role at different cancer stages.
AB  - Transforming growth factor-beta (TGF-beta) inhibits the proliferation of
      carcinomas in early stages of breast cancer, whereas it promotes tumor growth and
      metastasis in later stages of cancer. We evaluated a possible association between
      TGF-beta1 gene polymorphisms and breast cancer risk in a population-based case
      control study of Chinese women living in Shanghai, which included 1,127 breast
      cancer cases and 1,228 population controls. Two polymorphisms, C-509T and T+29C,
      were in strong linkage disequilibrium. There were no overall differences in the
      genotype distribution of T+29C polymorphisms of the TGF-beta1 gene among cases
      and controls. However, the distribution of the high-activity C allele of T+29C
      polymorphisms differed by cancer stages (P(trend) = 0.02). This allele was
      associated with decreased risk of early-stage breast cancer [stages 0 and I; odds
      ratio (OR), 0.73; 95% confidence interval (95% CI), 0.54-0.99], and the OR was
      further reduced to 0.66 (95% CI, 0.45-0.96) for those homozygous for this allele
      (P(trend) = 0.03). On the other hand, the same allele was associated with
      nonsignificantly increased risk of breast cancer with advanced stages III and IV
      (OR, 1.33; 95% CI, 0.81-2.18), which differed significantly from that observed
      for early-stage cancer (P = 0.04). This result suggests a possible dual effect of
      TGF-beta1 shown by in vitro experiments and provides an explanation for some of
      the inconsistent findings from previous epidemiologic studies that did not
      evaluate this association by cancer stage.

PMID- 15941975
TI  - Lack of association of physical activity and obesity with incident pancreatic
      cancer in elderly women.

PMID- 15941976
TI  - No association between dietary glycemic index or load and pancreatic cancer
      incidence in postmenopausal women.

PMID- 15941977
TI  - Common leptin receptor polymorphisms do not modify the effect of alcohol
      ingestion on serum leptin levels in a controlled feeding and alcohol ingestion
      study.
AB  - We explored whether serum leptin response to alcohol ingestion was related to
      common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg),
      S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic
      significance during a controlled intervention. Fifty-three participants rotated
      through three 8-week treatment periods and consumed 0, 15 (equivalent to one
      drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces
      of orange juice) per day, in random order. During the controlled feeding periods,
      all food and beverages including alcoholic beverages were prepared and supplied
      by the staff of the Beltsville Human Nutrition Research Center's Human Study
      Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant
      weight. Blood was collected after an overnight fast on 3 separate days during the
      last week of each controlled feeding period and pooled for hormone analysis.
      Circulating serum leptin concentration was measured in duplicate by RIA and
      genotype analysis was done on DNA extracted from WBC using real-time PCR analysis
      amplification (TaqMan). Linear mixed models with a single random intercept
      reflecting a participant effect were used to estimate changes in serum leptin
      levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No
      significant effects were found between common leptin receptor polymorphisms and
      serum leptin levels (P > or = 0.26).

PMID- 15941978
TI  - Robustness of case-control studies to population stratification.

PMID- 15941979
TI  - Subsite-specific colorectal cancer in diabetic and nondiabetic patients.

PMID- 15941980
TI  - Accuracy and reproducibility of short tandem repeat assays.

PMID- 15941981
TI  - Genome update: prediction of secreted proteins in 225 bacterial proteomes.

PMID- 15941982
TI  - Transcriptional takeover by sigma appropriation: remodelling of the sigma70
      subunit of Escherichia coli RNA polymerase by the bacteriophage T4 activator MotA
      and co-activator AsiA.
AB  - Activation of bacteriophage T4 middle promoters, which occurs about 1 min after
      infection, uses two phage-encoded factors that change the promoter specificity of
      the host RNA polymerase. These phage factors, the MotA activator and the AsiA co
      activator, interact with the sigma(70) specificity subunit of Escherichia coli
      RNA polymerase, which normally contacts the -10 and -35 regions of host promoter
      DNA. Like host promoters, T4 middle promoters have a good match to the canonical
      sigma(70) DNA element located in the -10 region. However, instead of the
      sigma(70) DNA recognition element in the promoter's -35 region, they have a 9 bp
      sequence (a MotA box) centred at -30, which is bound by MotA. Recent work has
      begun to provide information about the MotA/AsiA system at a detailed molecular
      level. Accumulated evidence suggests that the presence of MotA and AsiA
      reconfigures protein-DNA contacts in the upstream promoter sequences, without
      significantly affecting the contacts of sigma(70) with the -10 region. This type
      of activation, which is called 'sigma appropriation', is fundamentally different
      from other well-characterized models of prokaryotic activation in which an
      activator frequently serves to force sigma(70) to contact a less than ideal -35
      DNA element. This review summarizes the interactions of AsiA and MotA with
      sigma(70), and discusses how these interactions accomplish the switch to T4
      middle promoters by inhibiting the typical contacts of the C-terminal region of
      sigma(70), region 4, with the host -35 DNA element and with other subunits of
      polymerase.

PMID- 15941983
TI  - Acquisition of a stable mutation in metY allows efficient initiation from an
      amber codon in Escherichia coli.
AB  - Escherichia coli strains harbouring elongator tRNAs that insert amino acids in
      response to a termination codon during elongation have been generated for various
      applications. Additionally, it was shown that expression of an initiator tRNA
      containing a CUA anticodon from a multicopy plasmid in E. coli resulted in
      initiation from an amber codon. Even though the initiation-based system remedies
      toxicity-related drawbacks, its usefulness has remained limited for want of a
      strain with a chromosomally encoded initiator tRNA 'suppressor'. E. coli K
      strains possess four initiator tRNA genes: the metZ, metW and metV genes, located
      at a single locus, encode tRNA(1)(fMet), and a distantly located metY gene
      encodes a variant, tRNA(2)(fMet). In this study, a stable strain of E. coli K-12
      that affords efficient initiation from an amber initiation codon was isolated.
      Genetic analysis revealed that the metY gene in this strain acquired mutations to
      encode tRNA(2)(fMet) with a CUA anticodon (a U35A36 mutation). The acquisition of
      the mutations depended on the presence of a plasmid-borne copy of the mutant metY
      and recA(+) host background. The mutations were observed when the plasmid-borne
      gene encoded tRNA(2)(fMet) (U35A36) with additional changes in the acceptor stem
      (G72; G72G73) but not in the anticodon stem (U29C30A31/U35A36/psi39G40A41). The
      usefulness of this strain, and a possible role for multiple tRNA(1)(fMet) genes
      in E. coli in safeguarding their intactness, are discussed.

PMID- 15941984
TI  - The DNA-binding specificity of the Bacillus anthracis AbrB protein.
AB  - The Bacillus subtilis AbrB protein is a DNA-binding global regulator of a
      plethora of functions that are expressed during the transition from exponential
      growth to stationary phase and under suboptimal growth conditions. AbrB
      orthologues have been identified in a variety of prokaryotic organisms, notably
      in all species of Bacillus, Clostridium and Listeria that have been examined.
      Based on amino acid sequence identity in the N-terminal domains of the
      orthologues from B. subtilis and Bacillus anthracis, it was predicted that the
      proteins might display identical DNA-binding specificities. The binding of
      purified B. anthracis AbrB (AbrB(BA)) and purified B. subtilis AbrB (AbrB(BS)) at
      DNA targets of B. subtilis, B. anthracis and a synthetic origin was compared. In
      all cases examined, DNA-binding specificity was identical as judged by DNase I
      footprinting. In B. subtilis cells, the B. anthracis promoters from the atxA and
      abrB genes were regulated by AbrB(BS), and the B. subtilis promoter from the yxbB
      operon was regulated by AbrB(BA).

PMID- 15941985
TI  - Regulation of two highly similar genes, omcB and omcC, in a 10 kb chromosomal
      duplication in Geobacter sulfurreducens.
AB  - The Fe(III)-reducing micro-organism Geobacter sulfurreducens requires an outer
      membrane c-type cytochrome, OmcB, for Fe(III) reduction, but a related
      cytochrome, OmcC, which is 73 % identical to OmcB, is not required. The omcB and
      omcC genes are part of a tandem chromosomal duplication consisting of two
      repeated clusters of four genes. The 2.7 kb sequences preceding omcB and omcC are
      identical with the exception of a single base pair change. Studies that combined
      genetic, Northern blotting and primer extension analyses demonstrated that both
      omcB and omcC are transcribed as monocistronic and polycistronic (orf1-orf2
      omcB/omcC) transcripts. All of the promoters for the various transcripts were
      found to be located within the 2.7 kb identical region upstream of omcB and omcC.
      The sequences of the promoter regions for the two monocistronic transcripts are
      identical and equidistant from the omcB or omcC start codons. The promoters for
      the two polycistronic transcripts, in contrast, are distinct. One is specific for
      transcription of orf1-orf2-omcB and the other is associated with transcription of
      orf1-orf2-omcC. Studies with an RpoS-deficient mutant suggested that
      transcription from all four promoters is RpoS dependent under one or more growth
      conditions. Deletion of orfR, a gene immediately upstream of orf1-orf2-omcB that
      encodes a putative transcriptional regulator, significantly lowered the omcB
      transcription when Fe(III) was the electron acceptor and partially inhibited
      Fe(III) reduction. In contrast, levels of omcC transcripts were unaffected in the
      orfR mutant. These results indicate that omcB and omcC operons represent a rare
      instance in which duplicated operons, located in tandem on the chromosome, have
      different transcriptional regulation.

PMID- 15941986
TI  - The Bacillus subtilis YdfHI two-component system regulates the transcription of
      ydfJ, a member of the RND superfamily.
AB  - The ydfHI genes encode a sensor kinase and a response regulator forming a two
      component system. ydfJ is located downstream of ydfHI, and belongs to the RND
      (resistance-nodulation-cell division) superfamily, which is present in most major
      organisms. Four genes (secDF, yerP, ydfJ and ydgH) in Bacillus subtilis belong to
      this family. This study revealed that the YdfHI two-component system regulates
      ydfJ transcription. A gel shift assay using histidine-tagged YdfI (h-YdfI) showed
      that it directly binds to the ydfJ promoter region. Moreover, DNase I
      footprinting analysis revealed a tandem repeat sequence consisting of two
      conserved 12-mer sequences (GCCCRAAYGTAC) within the h-YdfI-binding site.

PMID- 15941988
TI  - sae is essential for expression of the staphylococcal adhesins Eap and Emp.
AB  - Eap and Emp are two Staphylococcus aureus adhesins initially described as
      extracellular matrix binding proteins. Eap has since emerged as being important
      in adherence to and invasion of eukaryotic cells, as well as being described as
      an immunomodulator and virulence factor in chronic infections. This paper
      describes the mapping of the transcription start point of the eap and emp
      promoters. Moreover, using reporter-gene assays and real-time PCR in defined
      regulatory mutants, environmental conditions and global regulators affecting
      expression of eap and emp were investigated. Marked differences were found in
      expression of eap and emp between strain Newman and the 8325 derivatives SH1000
      and 8325-4. Moreover, both genes were repressed in the presence of glucose.
      Analysis of expression of both genes in various regulatory mutants revealed that
      sarA and agr were involved in their regulation, but the data suggested that there
      were additional regulators of both genes. In a sae mutant, expression of both
      genes was severely repressed. sae expression was also reduced in the presence of
      glucose, suggesting that repression of eap and emp in glucose-containing medium
      may, in part, be a consequence of a decrease in expression of sae.

PMID- 15941987
TI  - Binding and transcriptional activation of non-flagellar genes by the Escherichia
      coli flagellar master regulator FlhD2C2.
AB  - The gene hierarchy directing biogenesis of peritrichous flagella on the surface
      of Escherichia coli and other enterobacteria is controlled by the
      heterotetrameric master transcriptional regulator FlhD(2)C(2). To assess the
      extent to which FlhD(2)C(2) directly activates promoters of a wider regulon, a
      computational screen of the E. coli genome was used to search for gene-proximal
      DNA sequences similar to the 42-44 bp inverted repeat FlhD(2)C(2) binding
      consensus. This identified the binding sequences upstream of all eight flagella
      class II operons, and also putative novel FlhD(2)C(2) binding sites in the
      promoter regions of 39 non-flagellar genes. Nine representative non-flagellar
      promoter regions were all bound in vitro by active reconstituted FlhD(2)C(2) over
      the K(D) range 38-356 nM, and of the nine corresponding chromosomal promoter-lacZ
      fusions, those of the four genes b1904, b2446, wzz(fepE) and gltI showed up to 50
      fold dependence on FlhD(2)C(2) in vivo. In comparison, four representative
      flagella class II promoters bound FlhD(2)C(2) in the K(D) range 12-43 nM and were
      upregulated in vivo 30- to 990-fold. The FlhD(2)C(2)-binding sites of the four
      regulated non-flagellar genes overlap by 1 or 2 bp the predicted -35 motif of the
      FlhD(2)C(2)-activated sigma(70) promoters, as is the case with FlhD(2)C(2)
      dependent class II flagellar promoters. The data indicate a wider FlhD(2)C(2)
      regulon, in which non-flagellar genes are bound and activated directly, albeit
      less strongly, by the same mechanism as that regulating the flagella gene
      hierarchy.

PMID- 15941989
TI  - Protein-protein interactions in the chemotaxis signalling pathway of Treponema
      denticola.
AB  - Motile bacteria employ sophisticated chemotaxis signal transduction systems to
      transform environmental cues into corresponding behavioural responses. The
      proteins involved in this signalling pathway have been extensively studied on a
      molecular level in various model organisms, including enterobacteria and Bacillus
      subtilis, and specific protein-protein interactions have been identified. The
      chemotaxis operon of spirochaetes encodes a novel chemotaxis protein, CheX, in
      addition to homologues to the central components of established chemotaxis
      systems. Interestingly, the closest functionally characterized homologue of CheX
      is CheC of the complex B. subtilis chemotaxis pathway. In this study, the yeast
      two-hybrid system was applied to investigate protein-protein interactions within
      the chemotaxis signalling pathway of Treponema denticola, with special focus on
      CheX. CheX was found to interact with CheA and with itself. The other chemotaxis
      proteins exhibited interactions comparable to their homologues in known
      chemotaxis systems. Based on these findings, a model integrating CheX in the
      chemotaxis signal transduction pathway of T. denticola is proposed.

PMID- 15941990
TI  - Three putative oxylipin biosynthetic genes integrate sexual and asexual
      development in Aspergillus nidulans.
AB  - Oxylipins called psi factors have been shown to alter the ratio of asexual to
      sexual sporulation in the filamentous fungus Aspergillus nidulans. Analysis of
      the A. nidulans genome has led to the identification of three fatty acid
      oxygenases (PpoA, PpoB and PpoC) predicted to produce psi factors. Here, it is
      reported that deletion of ppoB (DeltappoB) reduced production of the oleic-acid
      derived oxylipin psiBbeta and increased the ratio of asexual to sexual spore
      development. Generation of the triple mutant Delta ppoA Delta ppoB Delta ppoC
      resulted in a strain deficient in producing oleic- and linoleic-acid-derived 8'
      hydroxy psi factor and caused increased and mis-scheduled activation of sexual
      development. Changes in asexual to sexual spore development were positively
      correlated to alterations in the expression of brlA and veA, respectively. PpoB
      and/or its products antagonistically mediate the expression levels of ppoA and
      ppoC, thus revealing regulatory feedback loops among these three genes.
      Phylogenetic analyses showed that ppo genes are present in both saprophytic and
      pathogenic Ascomycetes and Basidiomycetes, suggesting a conserved role for Ppo
      enzymes in the life cycle of fungi.

PMID- 15941991
TI  - Up-regulation of competence- but not stress-responsive proteins accompanies an
      altered metabolic phenotype in Streptococcus mutans biofilms.
AB  - Mature biofilm and planktonic cells of Streptococcus mutans cultured in a neutral
      pH environment were subjected to comparative proteome analysis. Of the 242
      protein spots identified, 48 were significantly altered in their level of
      expression (P<0.050) or were unique to planktonic or biofilm-grown cells. Among
      these were four hypothetical proteins as well as proteins known to be associated
      with the maintenance of competence or found to possess a cin-box-like element
      upstream of their coding gene. Most notable among the non-responsive genes were
      those encoding the molecular chaperones DnaK, GroEL and GroES, which are
      considered to be up-regulated by sessile growth. Analysis of the rest of the
      proteome indicated that a number of cellular functions associated with carbon
      uptake and cell division were down-regulated. The data obtained were consistent
      with the hypothesis that a reduction in the general growth rate of mature
      biofilms of S. mutans in a neutral pH environment is associated with the
      maintenance of transformation without the concomitant stress response observed
      during the transient state of competence in bacterial batch cultures.

PMID- 15941992
TI  - Comparative analysis of the exopolysaccharide biosynthesis gene clusters from
      four strains of Lactobacillus rhamnosus.
AB  - The exopolysaccharide (EPS) biosynthesis gene clusters of four Lactobacillus
      rhamnosus strains consist of chromosomal DNA regions of 18.5 kb encoding 17 ORFs
      that are highly similar among the strains. However, under identical conditions,
      EPS production varies considerably among these strains, from 61 to 1611 mg l(-1).
      Fifteen genes are co-transcribed starting from the first promoter upstream of
      wzd. Nevertheless, five transcription start sites were identified by 5'-RACE PCR
      analysis, and these were associated with promoter sequences upstream of wzd,
      rmlA, welE, wzr and wzb. Six potential glycosyltransferase genes were identified
      that account for the assembly of the heptasaccharide repeat unit containing an
      unusually high proportion of rhamnose. Four genes involved in the biosynthesis of
      the sugar nucleotide precursor dTDP-L-rhamnose were identified in the EPS
      biosynthesis locus, which is unusual for lactic acid bacteria. These four genes
      are expressed from their own promoter (P2), as well as co-transcribed with the
      upstream EPS genes, resulting in coordinated production of the rhamnose precursor
      with the enzymes involved in EPS biosynthesis. This is believed to be the first
      report demonstrating that the sequence, original organization and transcription
      of genes encoding EPS production are highly similar among four strains of Lb.
      rhamnosus, and do not vary with the amount of EPS produced.

PMID- 15941993
TI  - The native Pseudomonas stutzeri strain Q chromosomal integron can capture and
      express cassette-associated genes.
AB  - The integron-gene cassette system contributes to multiple antibiotic resistance
      in bacteria and is likely to be of broader evolutionary significance. However,
      the majority of integron diversity consists of chromosomal integrons (CIs), with
      mostly unknown phenotypes, which are poorly characterized. A pUC-based reporter
      plasmid (pUS23) was developed containing a recombination site [aadB 59 base
      element (59-be)] upstream of promoterless aadB [gentamicin (Gm) resistance] and
      gfp (green fluorescence) genes, and this construct was used to investigate the
      recombination and expression activities of the CI in Pseudomonas stutzeri strain
      Q. Electroporation of pUS23 into P. stutzeri Q gave ampicillin-resistant
      transformants, which yielded Gm(R) green fluorescent recombinants after plating
      on Gm medium. Site-specific integration of pUS23 at attI was detected by PCR in 8
      % of Gm(R) colonies and the frequency of attI integration was estimated as 2.0 x
      10(-8) per P. stutzeri Q(pUS23) cell. RT-PCR confirmed integron-mediated
      expression of aadB in one recombinant strain (Q23-17) and a promoter (P(c)) was
      localized to the 5' end of the intI gene. The integrated pUS23 and flanking
      integron DNA were cloned from genomic DNA of strain Q23-17 and sequenced,
      confirming that site-specific integration of the entire reporter plasmid had
      occurred at the attI site. An insertion sequence (ISPst5; IS5 family) was
      discovered in the vector backbone of the reporter plasmid integrated at attI and
      also in a pUS23 derivative recovered as a plasmid in Escherichia coli JM109. This
      is the first demonstration that wild-type CIs can capture gene cassettes and
      express cassette-associated genes.

PMID- 15941994
TI  - Mutations affecting predation ability of the soil bacterium Myxococcus xanthus.
AB  - Myxococcus xanthus genetic mutants with characterized phenotypes were analysed
      for the ability to prey on susceptible bacteria. Quantification of predatory
      ability was scored by a newly developed method under conditions in which prey
      bacteria provided the only source of nutrients. These results were corroborated
      by data derived using a previously published protocol that measures predation in
      the presence of limited external nutrients. First, early developmental regulatory
      mutants were examined, because their likely functions in assessing the local
      nutrient status were predicted to be also important for predation. The results
      showed that predation efficiency is reduced by 64-80 % for mutants of three A
      signalling components, AsgA, AsgC and AsgE, but not for AsgB. This suggests that
      an Asg regulon function that is separate from A-signal production is needed for
      predation. Besides the Asg components, mutations in the early developmental genes
      sdeK and csgA were also consistently observed to reduce predatory efficacy by 36
      and 33 %, respectively. In contrast, later developmental components, such as
      DevRS, 4406 and PhoP4, did not appear to play significant roles in predation. The
      predatory abilities of mutants defective for motility were also tested. The data
      showed that adventurous, but not social, motility is required for predation in
      the assay. Also, mutants for components in the chemotaxis-like Frz system were
      found to be reduced in predation efficiency by between 62 and 85 %. In sum, it
      was demonstrated here that defects in development and development-related
      processes affect the ability of M. xanthus to prey on other bacteria.

PMID- 15941995
TI  - Population structure of group B streptococcus from a low-incidence region for
      invasive neonatal disease.
AB  - The population structure of group B streptococcus (GBS) from a low-incidence
      region for invasive neonatal disease (Israel) was investigated using multilocus
      genotype data. The strain collection consisted of isolates from maternal carriage
      (n=104) and invasive neonatal disease (n=50), resolving into 46 sequence types.
      The most prevalent sequence types were ST-1 (17.5 %), ST-19 (10.4 %), ST-17 (9.7
      %), ST-22 (8.4 %) and ST-23 (6.5 %). Serotype III was the most common, accounting
      for 29.2 % of the isolates. None of the serotypes was significantly associated
      with invasive neonatal disease. burst analysis resolved the 46 sequence types
      into seven lineages (clonal complexes), from which only lineage ST-17, expressing
      serotype III only, was significantly associated with invasive neonatal disease.
      Lineage ST-22 expressed mainly serotype II, and was significantly associated with
      carriage. The distribution of the various sequence types and lineages, and the
      association of lineage ST-17 with invasive disease, are consistent with the
      results of analyses from a global GBS isolate collection. These findings could
      imply that the global variation in disease incidence is independent of the
      circulating GBS populations, and may be more affected by other risk factors for
      invasive GBS disease, or by different prevention strategies.

PMID- 15941996
TI  - Use of molecular diversity of Mycoplasma gallisepticum by gene-targeted
      sequencing (GTS) and random amplified polymorphic DNA (RAPD) analysis for
      epidemiological studies.
AB  - A total of 67 Mycoplasma gallisepticum field isolates from the USA, Israel and
      Australia, and 10 reference strains, were characterized by gene-targeted
      sequencing (GTS) analysis of portions of the putative cytadhesin pvpA gene, the
      cytadhesin gapA gene, the cytadhesin mgc2 gene, and an uncharacterized
      hypothetical surface lipoprotein-encoding gene designated genome coding DNA
      sequence (CDS) MGA_0319. The regions of the surface-protein-encoding genes
      targeted in this analysis were found to be stable within a strain, after
      sequencing different in vitro passages of M. gallisepticum reference strains.
      Gene sequences were first analysed on the basis of gene size polymorphism. The
      pvpA and mgc2 genes are characterized by the presence of different nucleotide
      insertions/deletions. However, differentiation of isolates based solely on
      pvpA/mgc2 PCR size polymorphism was not found to be a reliable method to
      differentiate among M. gallisepticum isolates. On the other hand, GTS analysis
      based on the nucleotide sequence identities of individual and multiple genes
      correlated with epidemiologically linked isolates and with random amplified
      polymorphic DNA (RAPD) analysis. GTS analysis of individual genes, gapA,
      MGA_0319, mgc2 and pvpA, identified 17, 16, 20 and 22 sequence types,
      respectively. GTS analysis using multiple gene sequences mgc2/pvpa and
      gapA/MGA_0319/mgc2/pvpA identified 38 and 40 sequence types, respectively. GTS of
      multiple surface-protein-encoding genes showed better discriminatory power than
      RAPD analysis, which identified 36 pattern types from the same panel of M.
      gallisepticum strains. These results are believed to provide the first evidence
      that typing of M. gallisepticum isolates by GTS analysis of surface-protein genes
      is a sensitive and reproducible typing method and will allow rapid global
      comparisons between laboratories.

PMID- 15941997
TI  - Identification and regulation of cold-inducible factors of Bordetella
      bronchiseptica.
AB  - The expression of bacterial cold-shock proteins (CSPs) is highly induced in
      response to cold shock, and some CSPs are essential for cells to resume growth at
      low temperature. Bordetella bronchiseptica encodes five CSPs (named CspA to CspE)
      with significant amino acid homology to CspA of Escherichia coli. In contrast to
      E. coli, the insertional knock-out of a single csp gene (cspB) strongly affected
      growth of B. bronchiseptica independent of temperature. In the case of three of
      the csp genes (cspA, cspB, cspC) more than one specific transcript could be
      detected. The net amount of cspA, cspB and cspC transcripts increased strongly
      after cold shock, while no such effect could be observed for cspD and cspE. The
      exposure to other stress conditions, including translation inhibitors, heat
      shock, osmotic stress and nutrient deprivation in the stationary phase, indicated
      that the csp genes are also responsive to these conditions. The coding regions of
      all of the cold-shock genes are preceded by a long non-translated upstream region
      (5'-UTR). In the case of the cspB gene, a deletion of parts of this region led to
      a significant reduction of translation of the resulting truncated transcript,
      indicating a role of the 5'-UTR in translational control. The cold-shock stimulon
      was investigated by 2D-PAGE and mass spectrometric characterization, leading to
      the identification of additional cold-inducible proteins (CIPs). Interestingly,
      two cold-shock genes (cspC and cspD) were found to be under the negative control
      of the BvgAS system, the main transcriptional regulator of Bordetella virulence
      genes. Moreover, a negative effect of slight overexpression of CspB, but not of
      the other CSPs, on the transcription of the adenylate cyclase toxin CyaA of
      Bordetella pertussis was observed, suggesting cross-talk between the CSP-mediated
      stress response stimulon and the Bordetella virulence regulon.

PMID- 15941998
TI  - Immobilization-based isolation of capsule-negative mutants of Streptococcus
      pneumoniae.
AB  - The capsular polysaccharide (CPS) is the most important identified virulence
      factor of Streptococcus pneumoniae, a human pathogen of the upper respiratory
      tract. One limitation in studies of S. pneumoniae surface virulence factors is
      the lack of a reliable procedure for isolation of capsule-negative mutants of
      clinical strains. This paper presents an approach, based on the immobilization of
      pneumococci in semi-liquid (0.04 % agar) medium, to easily distinguish and select
      for non-capsulated mutants. A clinical S. pneumoniae type 37 strain was used as a
      model to show that CPS production results in bacterial immobilization in semi
      liquid agar medium and restricts cell sedimentation. Descendants of CPS(-)
      mutants sedimented faster under these conditions and therefore could be separated
      from immobilized parental cells. The CPS(-) phenotype of the obtained mutants was
      confirmed by both immunoagglutination and immunostaining experiments using
      specific type 37 capsular antibodies. Complementation of immobilization with the
      cloned tts gene, encoding type 37 CPS synthase, confirmed that faster
      sedimentation of mutants was specifically due to loss of the capsule. DNA
      sequence determination of three independent mutants revealed a point mutation, a
      46 nt deletion and a heptanucleotide duplication in the tts gene. Immobilization
      of strains producing other CPSs (type 2, 3 and 6) also resulted in the appearance
      of CPS(-) mutants, thus showing that immobilization-based isolation is not
      restricted to type 37 pneumococci. Bacterial growth in semi-liquid medium proved
      to be a useful model system to identify the genetic consequences of
      immobilization. The results indicate that immobilization due to CPS may impose
      selective pressure against capsule production and thus contribute to capsule
      plasticity.

PMID- 15941999
TI  - Oral immunization with a dam mutant of Yersinia pseudotuberculosis protects
      against plague.
AB  - Inactivation of the gene encoding DNA adenine methylase (dam) has been shown to
      attenuate some pathogens such as Salmonella enterica serovar Typhimurium and is a
      lethal mutation in others such as Yersinia pseudotuberculosis strain YPIII. In
      this study the dam methylase gene in Yersinia pseudotuberculosis strain IP32953
      was inactivated. Unlike the wild-type, DNA isolated from the mutant could be
      digested with MboI, which is consistent with an altered pattern of DNA
      methylation. The mutant was sensitive to bile salts but not to 2-aminopurine. The
      effect of dam inactivation on gene expression was examined using a DNA
      microarray. In BALB/c mice inoculated orally or intravenously with the dam
      mutant, the median lethal dose (MLD) was at least 10(6)-fold higher than the MLD
      of the wild-type. BALB/c mice inoculated with the mutant were protected against a
      subcutaneous challenge with 100 MLDs of Yersinia pestis strain GB and an
      intravenous challenge with 300 MLDs of Y. pseudotuberculosis IP32953.

PMID- 15942000
TI  - Photo-oxidative stress in Rhodobacter sphaeroides: protective role of carotenoids
      and expression of selected genes.
AB  - In Rhodobacter sphaeroides, carotenoids are essential constituents of the
      photosynthetic apparatus and are assumed to prevent the formation of singlet
      oxygen by quenching of triplet bacteriochlorophyll a (BChl a) in vivo. It was
      shown that small amounts of singlet oxygen are generated in vivo by incubation of
      R. sphaeroides under high light conditions. However, growth and survival rates
      were not affected. Higher amounts of singlet oxygen were generated by BChl a in a
      carotenoid-deficient strain and led to a decrease in growth and survival rates.
      The data support earlier results on the pivotal role of carotenoids in the
      defence against stress caused by singlet oxygen. Results obtained under photo
      oxidative stress conditions with strains impaired in carotenoid synthesis suggest
      that sphaeroidene and neurosporene provide less protection against methylene-blue
      generated singlet oxygen than sphaeroidenone in vivo. Despite their protective
      function against singlet oxygen, relative amounts of carotenoids did not
      accumulate in R. sphaeroides wild-type cultures under photo-oxidative stress, and
      relative mRNA levels of phytoene dehydrogenase and sphaeroidene monooxygenase did
      not increase. In contrast, singlet oxygen specifically induced the expression of
      glutathione peroxidase and a putative Zn-dependent hydrolase, but mRNA levels of
      hydrogen-peroxide-degrading catalase E were not significantly affected by photo
      oxidative stress. Based on these results, it is suggested that singlet oxygen
      acts as a specific signal for gene expression in R. sphaeroides. Presumably
      transcriptional regulators exist to specifically induce the expression of genes
      involved in the response to stress caused by singlet oxygen.

PMID- 15942001
TI  - Oxidative protein damage causes chromium toxicity in yeast.
AB  - Oxidative damage in microbial cells occurs during exposure to the toxic metal
      chromium, but it is not certain whether such oxidation accounts for the toxicity
      of Cr. Here, a Saccharomyces cerevisiae sod1Delta mutant (defective for the Cu,Zn
      superoxide dismutase) was found to be hypersensitive to Cr(VI) toxicity under
      aerobic conditions, but this phenotype was suppressed under anaerobic conditions.
      Studies with cells expressing a Sod1p variant (Sod1(H46C)) showed that the
      superoxide dismutase activity rather than the metal-binding function of Sod1p was
      required for Cr resistance. To help identify the macromolecular target(s) of Cr
      dependent oxidative damage, cells deficient for the reduction of phospholipid
      hydroperoxides (gpx3Delta and gpx1Delta/gpx2Delta/gpx3Delta) and for the repair
      of DNA oxidation (ogg1Delta and rad30Delta/ogg1Delta) were tested, but were found
      not to be Cr-sensitive. In contrast, S. cerevisiae msraDelta (mxr1Delta) and
      msrbDelta (ycl033cDelta) mutants defective for peptide methionine sulfoxide
      reductase (MSR) activity exhibited a Cr sensitivity phenotype, and cells
      overexpressing these enzymes were Cr-resistant. Overexpression of MSRs also
      suppressed the Cr sensitivity of sod1Delta cells. The inference that protein
      oxidation is a primary mechanism of Cr toxicity was corroborated by an observed
      approximately 20-fold increase in the cellular levels of protein carbonyls within
      30 min of Cr exposure. Carbonylation was not distributed evenly among the
      expressed proteins of the cells; certain glycolytic enzymes and heat-shock
      proteins were specifically targeted by Cr-dependent oxidative damage. This study
      establishes an oxidative mode of Cr toxicity in S. cerevisiae, which primarily
      involves oxidative damage to cellular proteins.

PMID- 15942002
TI  - NovG, a DNA-binding protein acting as a positive regulator of novobiocin
      biosynthesis.
AB  - The biosynthetic gene cluster of the aminocoumarin antibiotic novobiocin contains
      two putative regulatory genes, i.e. novE and novG. The predicted gene product of
      novG shows a putative helix-turn-helix DNA-binding motif and shares sequence
      similarity with StrR, a well-studied pathway-specific transcriptional activator
      of streptomycin biosynthesis. Here functional proof is provided, by genetic and
      biochemical approaches, for the role of NovG as a positive regulator of
      novobiocin biosynthesis. The entire novobiocin cluster of the producer organism
      Streptomyces spheroides was expressed in the heterologous host Streptomyces
      coelicolor M512, and additional strains were produced which lacked the novG gene
      within the heterologously expressed cluster. These Delta novG strains produced
      only 2% of the novobiocin formed by the S. coelicolor M512 strains carrying the
      intact novobiocin cluster. The production could be restored by introducing an
      intact copy of novG into the mutant. The presence of novG on a multicopy plasmid
      in the strain containing the intact cluster led to almost threefold
      overproduction of the antibiotic, suggesting that novobiocin biosynthesis is
      limited by the availability of NovG protein. Furthermore, purified N-terminal
      His(6)-tagged NovG showed specific DNA-binding activity for the novG-novH and the
      cloG-cloY intergenic regions of the novobiocin and clorobiocin biosynthetic gene
      clusters, respectively. By comparing the DNA sequences of the fragments binding
      NovG, conserved inverted repeats were identified in both fragments, similar to
      those identified as the binding sites for StrR. The consensus sequence for the
      StrR and the putative NovG binding sites was GTTCRACTG(N)(11)CRGTYGAAC.
      Therefore, NovG and StrR apparently belong to the same family of DNA-binding
      regulatory proteins.

PMID- 15942003
TI  - An acyl-CoA dehydrogenase is involved in the formation of the Delta cis3 double
      bond in the acyl residue of the lipopeptide antibiotic friulimicin in
      Actinoplanes friuliensis.
AB  - The lipopeptide antibiotic friulimicin, produced by Actinoplanes friuliensis, is
      an effective drug against Gram-positive bacteria, such as methicillin-resistant
      Staphylococcus epidermidis and Staphylococcus aureus strains. Friulimicin
      consists of a cyclic peptide core of ten amino acids and an acyl residue linked
      to an exocyclic amino acid. The acyl residue is essential for antibiotic
      activity, varies in length from C13 to C15, and carries a characteristic double
      bond at position Delta cis3. Sequencing of a DNA fragment adjacent to a
      previously described fragment encoding some of the friulimicin biosynthetic genes
      revealed several genes whose gene products resemble enzymes of lipid metabolism.
      One of these genes, lipB, encodes an acyl-CoA dehydrogenase homologue. To
      elucidate the function of the LipB protein, a lipB insertion mutant was generated
      and the friulimicin derivative (FR242) produced by the mutant was purified. FR242
      had antibiotic activity lower than friulimicin in a bioassay. Gas chromatography
      showed that the acyl residue of wild-type friulimicin contains a double bond,
      whereas a saturated bond was present in FR242. These results were confirmed by
      the heterologous expression of lipB in Streptomyces lividans T7, which led to the
      production of unsaturated fatty acids not found in the S. lividans T7 parent
      strain. These results indicate that the acyl-CoA dehydrogenase LipB is involved
      in the introduction of the unusual Delta cis3 double bond into the acyl residue
      of friulimicin.

PMID- 15942004
TI  - A minor catalase/peroxidase from Burkholderia cenocepacia is required for normal
      aconitase activity.
AB  - The opportunistic bacterium Burkholderia cenocepacia C5424 contains two
      catalase/peroxidase genes, katA and katB. To investigate the functions of these
      genes, katA and katB mutants were generated by targeted integration of suicide
      plasmids into the katA and katB genes. The catalase/peroxidase activity of the
      katA mutant was not affected as compared with that of the parental strain, while
      no catalase/peroxidase activity was detected in the katB mutant. However, the
      katA mutant displayed reduced resistance to hydrogen peroxide under iron
      limitation, while the katB mutant showed hypersensitivity to hydrogen peroxide,
      and reduced growth under all conditions tested. The katA mutant displayed reduced
      growth only in the presence of carbon sources that are metabolized through the
      tricarboxylic acid (TCA) cycle, as the growth defect was abrogated in cultures
      supplemented with glucose or glycerol. This phenotype was also correlated with a
      marked reduction in aconitase activity. In contrast, aconitase activity was not
      reduced in the katB mutant and parental strains. The authors conclude that the
      KatA protein is a specialized catalase/peroxidase that has a novel function by
      contributing to maintain the normal activity of the TCA cycle, while KatB is a
      classical catalase/peroxidase that plays a global role in cellular protection
      against oxidative stress.

PMID- 15942005
TI  - The specificity of oligopeptide transport by Streptococcus thermophilus resembles
      that of Lactococcus lactis and not that of pathogenic streptococci.
AB  - Peptide transport is a crucial step in the growth of Streptococcus thermophilus
      in protein- or peptide-containing media. The objective of the present work was to
      determine the specificity of peptide utilization by this widely used lactic acid
      bacterium. To reach that goal, complementary approaches were employed. The
      capability of a proteinase-negative S. thermophilus strain to grow in a
      chemically defined medium containing a mixture of peptides isolated from milk as
      the source of amino acids was analysed. Peptides were separated into three size
      classes by ultrafiltration. The strain was able to use peptides up to 3.5 kDa
      during growth, as revealed by liquid chromatography and mass spectrometry
      analyses. The same strain was grown in chemically defined medium containing a
      tryptic digest of casein, and the respective time-course consumption of the
      peptides during growth was estimated. The ability to consume large peptides (up
      to 23 residues) was confirmed, as long as they are cationic and hydrophobic.
      These results were confirmed by peptide transport studies. Extension of the study
      to 11 other strains revealed that they all shared these preferences.

PMID- 15942006
TI  - Plasma membrane H+ and K+ transporters are involved in the weak-acid preservative
      response of disparate food spoilage yeasts.
AB  - The food spoilage yeasts Zygosaccharomyces bailii and Saccharomyces cerevisiae
      have been proposed to resist weak-acid preservative stress by different means; Z.
      bailii by limiting influx of preservative combined with its catabolism, S.
      cerevisiae by active extrusion of the preservative weak-acid anion and H(+).
      Measurement of H(+) extrusion by exponential-phase Z. bailii cells suggest that,
      in common with S. cerevisiae, this yeast uses a plasma membrane H(+)-ATPase to
      expel H(+) when challenged by weak-acid preservative (benzoic acid). Simultaneous
      measurement of Z. bailii net H(+) and K(+) fluxes showed that net K(+) influx
      accompanies net H(+) efflux during acute benzoic acid stress. Such ionic coupling
      is known for S. cerevisiae in short-term preservative stress. Both yeasts
      significantly accumulated K(+) on long-term exposure to benzoic acid. Analysis of
      S. cerevisiae K(+) transporter mutants revealed that loss of the high affinity
      K(+) uptake system Trk1 confers sensitivity to growth in preservative. The
      results suggest that cation accumulation is an important factor in adaptation to
      weak-acid preservatives by spoilage yeasts and that Z. bailii and S. cerevisiae
      share hitherto unsuspected adaptive responses at the level of plasma membrane ion
      transport.

PMID- 15942007
TI  - The ferric iron uptake regulator (Fur) from the extreme acidophile
      Acidithiobacillus ferrooxidans.
AB  - Acidithiobacillus ferrooxidans is a Gram-negative bacterium that lives at pH 2 in
      high concentrations of soluble ferrous and ferric iron, making it an interesting
      model for understanding the biological mechanisms of bacterial iron uptake and
      homeostasis in extremely acid conditions. A candidate fur(AF) (Ferric Uptake
      Regulator) gene was identified in the A. ferrooxidans ATCC 23270 genome. Fur(AF)
      has significant sequence similarity, including conservation of functional motifs,
      to known Fur orthologues and exhibits cross-reactivity to Escherichia coli Fur
      antiserum. The fur(AF) gene is able to complement fur deficiency in E. coli in an
      iron-responsive manner. Fur(AF) is also able to bind specifically to E. coli Fur
      regulatory regions (Fur boxes) and to a candidate Fur box from A. ferrooxidans,
      as judged by electrophoretic mobility shift assays. Fur(AF) represses gene
      expression from E. coli Fur-responsive promoters fiu and fhuF when expressed at
      high protein levels. However, it increases gene expression from these promoters
      at low concentrations and possibly from other Fur-regulated promoters involved in
      iron-responsive oxidative stress responses.

PMID- 15942008
TI  - The leucyl aminopeptidase from Helicobacter pylori is an allosteric enzyme.
AB  - This study describes the cloning, genetic analysis and biochemical
      characterization of a leucyl aminopeptidase (LAP) from Helicobacter pylori. A
      gene encoding LAP was cloned from H. pylori and the expressed 55 kDa protein
      displayed homology to aminopeptidases from Gram-negative bacteria, plants and
      mammals. This LAP demonstrated amidolytic activity against L-leucine-p
      nitroanilide. Optimal activity was observed at pH 8.0 and 45 degrees C, with
      V(max) of 232 mumol min(-1) (mg protein)(-1) and S(0.5) of 0.65 mM. The data
      suggest that LAP could be allosteric (n(H)=2.27), with regulatory homohexamers,
      and its activity was inhibited by ion chelators and enhanced by divalent
      manganese, cobalt and nickel cations. Bestatin inhibited both LAP activity
      (IC(50)=49.9 nM) and H. pylori growth in vitro. The results point to the
      potential use of LAP as a drug target to develop novel anti-H. pylori agents.

PMID- 15942009
TI  - Structural and replicative diversity of large plasmids from sphingomonads that
      degrade polycyclic aromatic compounds and xenobiotics.
AB  - The plasmids from 16 sphingomonads which degrade various xenobiotics and
      polycyclic aromatic compounds were compared with the previously sequenced plasmid
      pNL1 from Sphingomonas aromaticivorans F199. The replicase genes repAaAb from
      plasmid pNL1 were amplified by PCR and used as a gene probe for the
      identification of plasmids belonging to the same incompatibility group as plasmid
      pNL1. Plasmids were prepared from various sphingomonads and hybridized with the
      repA gene probe. Positive hybridization signals were obtained with plasmids of
      approximately 160-195 kb from Sphingomonas subterranea and S. aromaticivorans
      B0695, which had been isolated from the same subsurface location as S.
      aromaticivorans F199. The repA probe also hybridized with plasmids from
      Sphingomonas xenophaga BN6, Sphingomonas sp. HH69 and Sphingomonas
      macrogoltabidus, which had been isolated from different continents and which
      utilize different organic compounds than S. aromaticivorans F199 and the other
      subsurface strains. The results of the hybridization experiments were confirmed
      by PCR experiments using primers deduced from the repAaAb region of plasmid pNL1.
      Nucleotide sequence comparisons suggested that three gene clusters were conserved
      between plasmid pNL1 and plasmid pBN6 from the naphthalenesulfonate- degrading
      strain S. xenophaga BN6. From these sequence comparisons, PCR primers were
      derived in order to detect the respective gene clusters in the other strains and
      to deduce their position relative to each other. These experiments demonstrated
      that all analysed subsurface strains harboured the same three gene clusters, but
      that the position and distance from each other of the clusters varied
      considerably among the different strains.

PMID- 15942010
TI  - A PCR-based specific assay reveals a population of bacteria within the
      Chloroflexi associated with the reductive dehalogenation of polychlorinated
      biphenyls.
AB  - Polychlorinated biphenyls (PCBs) accumulate and persist in sediments posing a
      risk to human health and the environment. Highly chlorinated PCBs are reductively
      dechlorinated in anaerobic sediments and two bacteria, designated o-17 and DF-1,
      from a novel phylogenetic group that reductively dechlorinate PCBs have recently
      been identified. However, there is a paucity of knowledge about the distribution,
      diversity and ecology of PCB-dechlorinating bacteria due to difficulty in
      obtaining pure cultures and the lack of detection by universal PCR 16S rRNA gene
      primer sets in sediments. A specific PCR primer was developed and optimized for
      detection of o-17/DF-1 and other closely related bacteria in the environment.
      Using this primer set it was determined that bacteria of this group were enriched
      in sediment microcosms from Baltimore Harbour concurrent with active
      dechlorination of 2,2',3,4,4',5'-hexachlorobiphenyl. Additional 16S rRNA gene
      sequences that had high levels of similarity to described PCB dechlorinators were
      detected in sediments from the Elizabeth River tributary of Chesapeake Bay, which
      had confirmed PCB-dechlorinating activities. Phylogenetic comparison of these
      detected 16S rRNA gene sequences revealed a relatively diverse group of organisms
      within the dehalogenating Chloroflexi that are distinct from the Dehalococcoides
      spp. Results from this study indicate that reductive PCB dechlorination activity
      may be catalysed by a previously undescribed group of micro-organisms that appear
      to be prevalent in PCB-impacted sites.

PMID- 15942011
TI  - Pectin utilization by the methylotrophic yeast Pichia methanolica.
AB  - The methylotrophic yeast Pichia methanolica was able to grow on pectic compounds,
      pectin and polygalacturonate, as sole carbon sources. Under the growth conditions
      used, P. methanolica exhibited increased levels of pectin methylesterase, and
      pectin-depolymerizing and methanol-metabolizing enzyme activities. On the other
      hand, P. methanolica has two alcohol oxidase (AOD) genes, MOD1 and MOD2. On
      growth on pectin, the P. methanolica mod1Delta and mod1Deltamod2Delta strains
      showed a severe defect in the growth yield, although the mod2Delta strain could
      grow on polygalacturonate to the same extent as the wild-type strain. The
      expression of MOD1 was detected in pectin-grown cells, but the MOD2-gene
      expression detected by pectin was much lower than that of MOD1. Moreover, pectin
      could induce peroxisome proliferation in P. methanolica, like methanol and oleic
      acid. These findings showed that P. methanolica was able to utilize the
      methylester moiety of pectin by means of methanol-metabolic enzymes in
      peroxisomes, and that the functional AOD subunit for pectin utilization was Mod1p
      in P. methanolica.

PMID- 15942012
TI  - ftsZ mutations affecting cell division frequency, placement and morphology in
      Bacillus subtilis.
AB  - A key event in cytokinesis in bacteria is the assembly of the essential division
      protein FtsZ into ring-like structures at the nascent division site. FtsZ is the
      prokaryotic homologue of tubulin, and is found in nearly all bacteria. In vitro,
      FtsZ polymerizes in the presence of GTP to form higher-ordered polymers. FtsZ
      consists of two domains, with the GTP-binding site located in the N-terminal
      domain. The less-conserved C-terminal domain contains residues important for GTP
      hydrolysis, but its overall function is still unclear. This paper reports the
      development of a simple strategy to generate mutations in the essential division
      gene ftsZ. Nine novel and viable ftsZ mutants of Bacillus subtilis are described.
      Eight of the mutations would affect the C-terminus of FtsZ. The collection of
      mutants exhibits a range of morphological phenotypes, ranging from normal to
      highly filamentous cells; some produce minicells, or divide in a twisted
      configuration; one mutation has a temperature-sensitive effect specifically
      impairing sporulation. The sites of the amino acid changes generated by the
      mutations could be informative about FtsZ function and its protein-protein
      interactions.

PMID- 15942013
TI  - Diverse humoral immune responses and changes in IgG antibody levels against
      mycobacterial lipid antigens in active tuberculosis.
AB  - Humoral immune responses of active TB patients against six mycobacterial lipid
      antigens [trehalose 6,6'-dimycolate (TDM) from Mycobacterium bovis BCG (TDM-T)
      and Mycobacterium avium complex (TDM-M), trehalose 6-monomycolate (TMM) from M.
      bovis BCG (TMM-T) and M. avium complex (TMM-M), triacyl (PL-2) and tetraacyl (PL
      1) phosphatidylinositol dimannosides] were examined by ELISA. IgG antibodies of
      TB patients with active disease reacted against the six lipid antigens
      distinctively, but heterogeneously. If tests were combined and an overall
      positive was scored cumulatively when any one of the six tests was positive, a
      good discrimination between patient and normal subject was obtained. A positive
      result in any one of the six tests was obtained in 91.5% of all 924 hospitalized
      patients and 93.3% of 210 patients at their first visit to the outpatient clinic.
      The IgG antibody response differed considerably from patient to patient, and the
      response patterns were grouped into several types. IgG antibody levels paralleled
      the bacterial burden; however, the smear-negative (culture-positive) patient
      group also showed high positive rates and mean ELISA DeltaA values against the
      six lipid antigens. There were also marked differences in positive rate and mean
      DeltaA values between cavity-positive and -negative groups, the former being
      higher than the latter. After anti-TB chemotherapy was initiated, IgG antibody
      levels decreased dramatically, paralleling the decrease in the amount of
      excretion of bacteria. Since multiple-antigen ELISA using particular lipid
      antigens was highly sensitive, and IgG antibody levels vary greatly at different
      stages of the disease, this technique is applicable for early diagnosis of smear
      negative (and -positive) active TB and the prognosis for completion of anti-TB
      chemotherapy.

PMID- 15942014
TI  - The cell envelope structure and properties of Mycobacterium smegmatis mc(2)155:
      is there a clue for the unique transformability of the strain?
AB  - Mycobacterium smegmatis is often used as a surrogate host for pathogenic
      mycobacteria, especially since the isolation of the transformable smooth
      morphotype strain mc(2)155 from the isogenic rough wild-type strain ATCC 607.
      Biochemical analysis of the cell envelope components revealed a lack of polar
      glycolipids, namely the lipooligosaccharides and the polar subfamilies of
      glycopeptidolipids, in the mc(2)155 strain. In addition, the latter strain
      differs from its parent by the distribution of various species of glycolipids and
      phospholipids between the outermost and deeper layers of the cell envelope. The
      presence of filamentous and rope-like structures at the cell surface of mc(2)155
      cells grown in complex media further supported an ultrastructural change in the
      cell envelope of the mutant. Importantly, a significantly more rapid uptake of
      the hydrophobic chenodeoxycholate was observed for the mutant compared to wild
      type cells. Taken together, these data indicate that the nature of the surface
      exposed and envelope constituents is crucial for the surface properties, cell
      wall permeability and bacterial phenotype, and suggest that the transformable
      character of the mc(2)155 strain may be in part explained by these profound
      modifications of its cell envelope.

PMID- 15942015
TI  - Altered expression profile of mycobacterial surface glycopeptidolipids following
      treatment with the antifungal azole inhibitors econazole and clotrimazole.
AB  - The azole antifungal drugs econazole and clotrimazole are known cytochrome P450
      enzyme inhibitors. This study shows that these drugs are potent inhibitors of
      mycobacterial growth and are more effective against Mycobacterium smegmatis than
      isoniazid and ethionamide, two established anti-mycobacterial drugs. Several non
      tuberculous mycobacteria, including the pathogenic members of the Mycobacterium
      avium-intracellulare complex (MAC) and the fast-growing saprophytic organism M.
      smegmatis, produce an array of serovar-specific (ss) and non-serovar-specific
      (ns) glycopeptidolipids (GPLs). GPL biosynthesis has been investigated for
      several years but has still not been fully elucidated. The authors demonstrate
      here that econazole and clotrimazole inhibit GPL biosynthesis in M. smegmatis. In
      particular, clotrimazole inhibits all four types of nsGPLs found in M. smegmatis,
      suggesting an early and common target within their biosynthetic pathway.
      Altogether, the data suggest that an azole-specific target, most likely a
      cytochrome P450, may be involved in the hydroxylation of the N-acyl chain in GPL
      biosynthesis. Azole antifungal drugs and potential derivatives could represent an
      interesting new range of anti-mycobacterial drugs, especially against
      opportunistic human pathogens including MAC, M. scrofulaceum, M. peregrinum, M.
      chelonae and M. abscessus.

PMID- 15942016
TI  - Comparison of Escherichia coli isolates implicated in human urinary tract
      infection and avian colibacillosis.
AB  - Since avian pathogenic Escherichia coli (APEC) and human uropathogenic E. coli
      (UPEC) may encounter similar challenges when establishing infection in
      extraintestinal locations, they may share a similar content of virulence genes
      and capacity to cause disease. In the present study, 524 APEC and 200 UPEC
      isolates were compared by their content of virulence genes, phylogenetic group,
      and other traits. The two groups showed substantial overlap in terms of their
      serogroups, phylogenetic groups and virulence genotypes, including their
      possession of certain genes associated with large transmissible plasmids of APEC.
      Based on these results, the propensity of both groups to cause extraintestinal
      infections, and a well-documented ability of avian E. coli to spread to human
      beings, the potential for APEC to act as human UPEC or as a reservoir of
      virulence genes for UPEC should be considered. However, significant differences
      in the prevalence of the traits occurred across the two groups, suggesting that
      if APEC are involved in human urinary tract infections, they are not involved in
      all of them.

PMID- 15942017
TI  - Attenuated virulence of an Aeromonas salmonicida subsp. salmonicida type III
      secretion mutant in a rainbow trout model.
AB  - Aeromonas salmonicida subsp. salmonicida is the causative agent of furunculosis,
      a severe systemic disease affecting salmonid fish. This bacterium contains a type
      III protein secretion system that is responsible for the secretion and
      translocation of the ADP-ribosylating toxin, AexT, into the cytosol of fish
      cells. This study showed that inactivation of the type III secretion system by
      marker-replacement mutagenesis of the gene ascV, which encodes an inner-membrane
      component of the type III secretion system, attenuated virulence in a rainbow
      trout model. The isogenic ascV deletion mutant was phagocytosed by peripheral
      blood leukocytes but the wild-type (wt) A. salmonicida subsp. salmonicida isolate
      was not. Histological examination of fish experimentally infected with the wt
      bacterium revealed extensive tissue necrosis and bacterial aggregates in all
      organs examined, including the heart, kidney and liver, indicating that the
      isolate established a systemic infection. Cumulative mortality of fish
      experimentally infected with the wt bacterium reached 88%. In contrast, no
      mortality was observed among fish infected with the same dose of the ascV mutant,
      and histological examination of fish infected with this strain revealed healthy
      organs. The results indicate that the type III secretion system of A. salmonicida
      subsp. salmonicida is required to establish systemic infection.

PMID- 15942018
TI  - Pathway analysis of coronary atherosclerosis.
AB  - Large-scale gene expression studies provide significant insight into genes
      differentially regulated in disease processes such as cancer. However, these
      investigations offer limited understanding of multisystem, multicellular diseases
      such as atherosclerosis. A systems biology approach that accounts for gene
      interactions, incorporates nontranscriptionally regulated genes, and integrates
      prior knowledge offers many advantages. We performed a comprehensive gene level
      assessment of coronary atherosclerosis using 51 coronary artery segments isolated
      from the explanted hearts of 22 cardiac transplant patients. After histological
      grading of vascular segments according to American Heart Association guidelines,
      isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray,
      and significance analysis of microarrays and gene ontology analyses were
      performed to identify significant gene expression profiles. Our studies revealed
      that loss of differentiated smooth muscle cell gene expression is the primary
      expression signature of disease progression in atherosclerosis. Furthermore, we
      provide insight into the severe form of coronary artery disease associated with
      diabetes, reporting an overabundance of immune and inflammatory signals in
      diabetics. We present a novel approach to pathway development based on
      connectivity, determined by language parsing of the published literature, and
      ranking, determined by the significance of differentially regulated genes in the
      network. In doing this, we identify highly connected "nexus" genes that are
      attractive candidates for therapeutic targeting and followup studies. Our use of
      pathway techniques to study atherosclerosis as an integrated network of gene
      interactions expands on traditional microarray analysis methods and emphasizes
      the significant advantages of a systems-based approach to analyzing complex
      disease.

PMID- 15942019
TI  - Gene expression profiling of experimental traumatic spinal cord injury as a
      function of distance from impact site and injury severity.
AB  - Changes in gene expression contribute to pathophysiological alterations following
      spinal cord injury (SCI). We examined gene expression over time (4 h, 24 h, 7
      days) at the impact site, as well as rostral and caudal regions, following mild,
      moderate, or severe contusion SCI in rats. High-density oligonucleotide
      microarrays were used that included approximately 27,000 genes/ESTs (Affymetrix
      RG-U34; A, B and C arrays), together with multiple analyses (MAS 5.0, dChip).
      Alterations after mild injury were relatively rapid (4 and 24 h), whereas they
      were delayed and prolonged after severe injury (24 h and 7 days). The number and
      magnitude of gene expression changes were greatest at the injury site after
      moderate injury and increased in rostral and caudal regions as a function of
      injury severity. Sham surgery resulted in expression changes that were similar to
      mild injury, suggesting the importance of using time-linked surgical controls as
      well as naive animals for these kinds of studies. Expression of many genes and
      ESTs was altered; these were classified functionally based on ontology. Overall
      representation of these functional classes varied with distance from the site of
      injury and injury severity, as did the individual genes that contributed to each
      functional class. Different clustering approaches were used to identify changes
      in neuronal-specific genes and several transcription factors that have not
      previously been associated with SCI. This study represents the most comprehensive
      evaluation of gene expression changes after SCI to date. The results underscore
      the power of microarray approaches to reveal global genomic responses as well as
      changes in particular gene clusters and/or families that may be important in the
      secondary injury cascade.

PMID- 15942020
TI  - A physiogenomic approach to study the regulation of blood pressure.
AB  - Several vasoregulatory systems including the renin-angiotensin system,
      sympathetic vasoregulation, and cytokine release have been studied extensively.
      The aim of the present study was to establish a physiogenomic screening model for
      differentially expressed genes in the regulation of blood pressure that might
      give a hint as to new vasoregulatory mechanisms. We induced acute hypotension in
      normotensive rats, assuming that vasoregulatory systems will counteract
      hypotension. Microarray transcriptome analysis was performed from kidneys 6 h
      after the induction of acute hypotension. The results were confirmed by real-time
      PCR. Six functionally known genes (Igfbp1, Xdh, Sult1a1, Mawbp, Por, and Gstm1)
      and two expressed sequence tages (BI277460 and AI411345) were significantly
      upregulated. Four of these genes (Igfbp1, Xdh, Por, and Gstm1) have well
      characterized functions in the cardiovascular system. The proteins corresponding
      to Xdh, Por, and Gstm1 are involved in the metabolism of reactive oxygen species
      (ROS). Because ROS can mediate endothelial dysfunction, we measured the aortic
      dilatory capacity in thoracic aortic rings. Indeed, vasodilator potency to
      acetylcholine was largely diminished in hypotensive animals, whereas sodium
      nitroprusside induced equivalent vasodilations in normotensive and hypotensive
      animals. The vasodilator potency of the endothelium was partially restored by the
      superoxide scavenger tiron. Hence, acute hypotension induces a diminished
      vasodilator potency of the endothelium due to an accelerated degradation of
      nitric oxide by ROS. The present physiogenomic approach is capable of detecting
      vasoregulatory mechanisms and may provide deeper insight into the genetics and
      physiology of blood pressure regulation.

PMID- 15942021
TI  - Gene expression profiling of hypoxia signaling in human hepatocellular carcinoma
      cells.
AB  - Cellular, local, and organismal responses to low O2 availability occur during
      processes such as anaerobic metabolism and wound healing and pathological
      conditions such as stroke and cancer. These responses include increases in
      glycolytic activity, vascularization, breathing, and red blood cell production.
      These responses are mediated in part by the hypoxia-inducible factors (HIFs),
      which receive information on O2 levels from a group of iron- and O2-dependent
      hydroxylases. Hypoxia mimics, such as cobalt chloride, nickel chloride, and
      deferoxamine, act to simulate hypoxia by altering the iron status of these
      hydroxylases. To determine whether these mimics are appropriate substitutes for
      the lower O2 tension evoked naturally, we compared transcriptional responses of a
      Hep3B cell line using high-density oligonucleotide arrays. A battery of core
      genes was identified that was shared by all four treatments (hypoxia, cobalt,
      nickel, and deferoxamine) including glycolytic enzymes, cell cycle regulators,
      and apoptotic genes. Importantly, cobalt, nickel, and deferoxamine influenced
      transcription of distinct sets of genes that were not affected by cellular
      hypoxia. These global responses to hypoxia indicate a balancing act between
      adaptation and programmed cell death and suggest caution in the use of hypoxia
      mimics as substitutes for the low O2 tension that occurs in vivo.

PMID- 15942022
TI  - Down-regulation of DNA topoisomerase IIalpha leads to prolonged cell cycle
      transit in G2 and early M phases and increased survival to microtubule
      interacting agents.
AB  - Microtubule binders are cell cycle-specific agents with preferential cytotoxicity
      toward mitotic cells. We have characterized vincristine-selected human leukemia
      cells to establish whether development of vincristine resistance was accompanied
      by changes in cell cycle kinetics and distribution. Our results indicate that
      vincristine resistance is accompanied by delayed G2 transit and prolonged early
      mitosis in both the absence and the presence of the microtubule binder
      nocodazole. The altered G2/M regulation is accompanied by resistance to short
      term (12 h) but not continuous nocodazole exposure in agreement with the
      transient nature of the observed cell cycle alterations. Western blot analysis
      indicates that vincristine-selection is accompanied by down-regulation of
      topoisomerase IIalpha without detectable alterations of the other mitotic
      regulators studied, including Cdk1, p21, 14-3-3sigma, and 14-3-3epsilon. This was
      associated with at least 7-fold less chromosome-associated topoisomerase IIalpha,
      decreased catalytic activity, and cross-resistance to topoisomerase II
      inhibitors. Characterization of isogenic cell lines expressing different levels
      of topoisomerase II proteins shows that cellular levels of topoisomerase IIalpha,
      but not the closely related topoisomerase IIbeta, directly influence the cell
      cycle kinetics in G2 and early mitosis as well as the resistance to nocodazole.
      These results underline the importance of topoisomerase IIalpha in late G2 and
      early M phases and provide evidence for an as-yet-unsuspected interaction between
      topoisomerase II and microtubule-directed agents.

PMID- 15942023
TI  - Genome amplification of single sperm using multiple displacement amplification.
AB  - Sperm typing is an effective way to study recombination rate on a fine scale in
      regions of interest. There are two strategies for the amplification of single
      meiotic recombinants: repulsion-phase allele-specific PCR and whole genome
      amplification (WGA). The former can selectively amplify single recombinant
      molecules from a batch of sperm but is not scalable for high-throughput
      operation. Currently, primer extension pre-amplification is the only method used
      in WGA of single sperm, whereas it has limited capacity to produce high-coverage
      products enough for the analysis of local recombination rate in multiple large
      regions. Here, we applied for the first time a recently developed WGA method,
      multiple displacement amplification (MDA), to amplify single sperm DNA, and
      demonstrated its great potential for producing high-yield and high-coverage
      products. In a 50 mul reaction, 76 or 93% of loci can be amplified at least 2500-
      or 250-fold, respectively, from single sperm DNA, and second-round MDA can
      further offer >200-fold amplification. The MDA products are usable for a variety
      of genetic applications, including sequencing and microsatellite marker and
      single nucleotide polymorphism (SNP) analysis. The use of MDA in single sperm
      amplification may open a new era for studies on local recombination rates.

PMID- 15942024
TI  - RNA interference by mixtures of siRNAs prepared using custom oligonucleotide
      arrays.
AB  - RNA interference (RNAi) is a process in which double-strand RNA (dsRNA) directs
      the specific degradation of a corresponding target mRNA. The mediators of this
      process are small dsRNAs, of approximately 21 bp in length, called small
      interfering RNAs (siRNAs). siRNAs, which can be prepared in vitro in a number of
      ways and then transfected into cells, can direct the degradation of corresponding
      mRNAs inside these cells. Hence, siRNAs represent a powerful tool for studying
      gene functions, as well as having the potential of being highly specific
      pharmaceutical agents. Some limitations in using this technology exist because
      the preparation of siRNA in vitro and screening for siRNAs efficient in RNAi can
      be expensive and time-consuming processes. Here, we demonstrate that custom
      oligonucleotide arrays can be efficiently used for the preparation of defined
      mixtures of siRNAs for the silencing of exogenous and endogenous genes. The
      method is fast, inexpensive, does not require siRNA optimization and has a number
      of advantages over methods utilizing enzymatic preparation of siRNAs by digestion
      of longer dsRNAs, as well as methods based on chemical synthesis of individual
      siRNAs or their DNA templates.

PMID- 15942025
TI  - Interruptions in gene expression drive highly expressed operons to the leading
      strand of DNA replication.
AB  - In bacteria, most genes are on the leading strand of replication, a phenomenon
      attributed to collisions between the DNA and RNA polymerases. In Escherichia
      coli, these collisions slow the movement of the replication fork through actively
      transcribed genes only if they are coded on the lagging strand. For genes on both
      strands, however, these collisions sever nascent transcripts and interrupt gene
      expression. Based on these observations, we propose a new theory to explain
      strand bias: genes whose expression is important for fitness are selected to the
      leading strand because this reduces the duration of these interruptions. Our
      theory predicts that multi-gene operons, which are subject to longer
      interruptions, should be more strongly selected to the leading strand than
      singleton transcripts. We show that this is true even after controlling for the
      tendency for essential genes, which are strongly biased to the leading strand, to
      occur in operons. Our theory also predicts that other factors that are associated
      with strand bias should have stronger effects for genes that are in operons. We
      find that expression level and phylogenetic ubiquity are correlated with strand
      bias for both essential and non-essential genes, but only for genes in operons.

PMID- 15942026
TI  - DNA bending by M.EcoKI methyltransferase is coupled to nucleotide flipping.
AB  - The maintenance methyltransferase M.EcoKI recognizes the bipartite DNA sequence
      5'-AACNNNNNNGTGC-3', where N is any nucleotide. M.EcoKI preferentially methylates
      a sequence already containing a methylated adenine at or complementary to the
      underlined bases in the sequence. We find that the introduction of a single
      stranded gap in the middle of the non-specific spacer, of up to 4 nt in length,
      does not reduce the binding affinity of M.EcoKI despite the removal of non
      sequence-specific contacts between the protein and the DNA phosphate backbone.
      Surprisingly, binding affinity is enhanced in a manner predicted by simple
      polymer models of DNA flexibility. However, the activity of the enzyme declines
      to zero once the single-stranded region reaches 4 nt in length. This indicates
      that the recognition of methylation of the DNA is communicated between the two
      methylation targets not only through the protein structure but also through the
      DNA structure. Furthermore, methylation recognition requires base flipping in
      which the bases targeted for methylation are swung out of the DNA helix into the
      enzyme. By using 2-aminopurine fluorescence as the base flipping probe we find
      that, although flipping occurs for the intact duplex, no flipping is observed
      upon introduction of a gap. Our data and polymer model indicate that M.EcoKI
      bends the non-specific spacer and that the energy stored in a double-stranded
      bend is utilized to force or flip out the bases. This energy is not stored in
      gapped duplexes. In this way, M.EcoKI can determine the methylation status of two
      adenine bases separated by a considerable distance in double-stranded DNA and
      select the required enzymatic response.

PMID- 15942027
TI  - Visualizing the dynamic behavior of poliovirus plus-strand RNA in living host
      cells.
AB  - Dynamic analysis of viral nucleic acids in host cells is important for
      understanding virus-host interaction. By labeling endogenous RNA with molecular
      beacon, we have realized the direct visualization of viral nucleic acids in
      living host cells and have studied the dynamic behavior of poliovirus plus-strand
      RNA. Poliovirus plus-strand RNA was observed to display different distribution
      patterns in living Vero cells at different post-infection time points. Real-time
      imaging suggested that the translocation of poliovirus plus-strand RNA is a
      characteristic rearrangement process requiring intact microtubule network of host
      cells. Confocal-FRAP measurements showed that 49.4 +/- 3.2% of the poliovirus
      plus-strand RNA molecules diffused freely (with a D-value of 9.6 +/- 1.6 x 10(
      10) cm2/s) within their distribution region, while the remaining (50.5 +/- 2.9%)
      were almost immobile and moved very slowly only with change of the RNA
      distribution region. Under the electron microscope, it was found that virus
      induced membrane rearrangement is microtubule-associated in poliovirus-infected
      Vero cells. These results reveal an entrapment and diffusion mechanism for the
      movement of poliovirus plus-strand RNA in living mammalian cells, and demonstrate
      that the mechanism is mainly associated with microtubules and virus-induced
      membrane structures.

PMID- 15942028
TI  - A universally applicable method of operon map prediction on minimally annotated
      genomes using conserved genomic context.
AB  - An important step in understanding the regulation of a prokaryotic genome is the
      generation of its transcription unit map. The current strongest operon predictor
      depends on the distributions of intergenic distances (IGD) separating adjacent
      genes within and between operons. Unfortunately, experimental data on these
      distance distributions are limited to Escherichia coli and Bacillus subtilis. We
      suggest a new graph algorithmic approach based on comparative genomics to
      identify clusters of conserved genes independent of IGD and conservation of gene
      order. As a consequence, distance distributions of operon pairs for any arbitrary
      prokaryotic genome can be inferred. For E.coli, the algorithm predicts 854
      conserved adjacent pairs with a precision of 85%. The IGD distribution for these
      pairs is virtually identical to the E.coli operon pair distribution. Statistical
      analysis of the predicted pair IGD distribution allows estimation of a genome
      specific operon IGD cut-off, obviating the requirement for a training set in IGD
      based operon prediction. We apply the method to a representative set of eight
      genomes, and show that these genome-specific IGD distributions differ
      considerably from each other and from the distribution in E.coli.

PMID- 15942029
TI  - Predicting non-coding RNA genes in Escherichia coli with boosted genetic
      programming.
AB  - Several methods exist for predicting non-coding RNA (ncRNA) genes in Escherichia
      coli (E.coli). In addition to about sixty known ncRNA genes excluding tRNAs and
      rRNAs, various methods have predicted more than thousand ncRNA genes, but only 95
      of these candidates were confirmed by more than one study. Here, we introduce a
      new method that uses automatic discovery of sequence patterns to predict ncRNA
      genes. The method predicts 135 novel candidates. In addition, the method predicts
      152 genes that overlap with predictions in the literature. We test sixteen
      predictions experimentally, and show that twelve of these are actual ncRNA
      transcripts. Six of the twelve verified candidates were novel predictions. The
      relatively high confirmation rate indicates that many of the untested novel
      predictions are also ncRNAs, and we therefore speculate that E.coli contains more
      ncRNA genes than previously estimated.

PMID- 15942030
TI  - Phosphorylation of human oxoguanine DNA glycosylase (alpha-OGG1) modulates its
      function.
AB  - Oxoguanine DNA glycosylase (OGG1) initiates the repair of 8-oxoguanine (8-oxoG),
      a major oxidative DNA base modification that has been directly implicated in
      cancer and aging. OGG1 functions in the base excision repair pathway, for which a
      molecular hand-off mechanism has been proposed. To date, only one functional and
      a few physical protein interactions have been reported for OGG1. Using the yeast
      two-hybrid system and a protein array membrane, we identified two novel protein
      interactions of OGG1, with two different protein kinases: Cdk4, a serine
      threonine kinase, and c-Abl, a tyrosine kinase. We confirmed these interactions
      in vitro using recombinant proteins and in vivo by co-immunoprecipitation from
      whole cell extracts. OGG1 is phosphorylated in vitro by Cdk4, resulting in a 2.5
      fold increase in the 8-oxoG/C incision activity of OGG1. C-Abl tyrosine
      phosphorylates OGG1 in vitro; however, this phosphorylation event does not affect
      OGG1 8-oxoG/C incision activity. These results provide the first evidence that a
      post-translational modification of OGG1 can affect its catalytic activity. The
      distinct functional outcomes from serine/threonine or tyrosine phosphorylation
      may indicate that activation of different signal transduction pathways modulate
      OGG1 activity in different ways.

PMID- 15942031
TI  - Analysis of nuclear transport signals in the human apurinic/apyrimidinic
      endonuclease (APE1/Ref1).
AB  - The mammalian abasic-endonuclease1/redox-factor1 (APE1/Ref1) is an essential
      protein whose subcellular distribution depends on the cellular physiological
      status. However, its nuclear localization signals have not been studied in
      detail. We examined nuclear translocation of APE1, by monitoring enhanced green
      fluorescent protein (EGFP) fused to APE1. APE1's nuclear localization was
      significantly decreased by deleting 20 amino acid residues from its N-terminus.
      Fusion of APE1's N-terminal 20 residues directed nuclear localization of EGFP. An
      APE1 mutant lacking the seven N-terminal residues (ND7 APE1) showed nearly normal
      nuclear localization, which was drastically reduced when the deletion was
      combined with the E12A/D13A double mutation. On the other hand, nearly normal
      nuclear localization of the full-length E12A/D13A mutant suggests that the first
      7 residues and residues 8-13 can independently promote nuclear import. Both far
      western analyses and immuno-pull-down assays indicate interaction of APE1 with
      karyopherin alpha 1 and 2, which requires the 20 N-terminal residues and
      implicates nuclear importins in APE1's nuclear translocation. Nuclear
      accumulation of the ND7 APE1(E12A/D13A) mutant after treatment with the nuclear
      export inhibitor leptomycin B suggests the presence of a previously unidentified
      nuclear export signal, and the subcellular distribution of APE1 may be regulated
      by both nuclear import and export.

PMID- 15942032
TI  - Formation of a large, complex domain of histone hyperacetylation at human 14q32.1
      requires the serpin locus control region.
AB  - The human serine protease inhibitor (serpin) gene cluster at 14q32.1 is a useful
      model system to study cell-type-specific gene expression and chromatin structure.
      Activation of the serpin locus can be induced in vitro by transferring human
      chromosome 14 from non-expressing to expressing cells. Serpin gene activation in
      expressing cells is correlated with locus-wide alterations in chromatin
      structure, including the de novo formation of 17 expression-associated DNase I
      hypersensitive sites (DHSs). In this study, we investigated histone acetylation
      throughout the proximal serpin subcluster. We report that gene activation is
      correlated with high levels of histone H3 and H4 acetylation at serpin gene
      promoters and other regulatory regions. However, the locus is not uniformly
      hyperacetylated, as there are regions of hypoacetylation between genes.
      Furthermore, genetic tests indicate that locus-wide controls regulate both gene
      expression and chromatin structure. For example, deletion of a previously
      identified serpin locus control region (LCR) upstream of the proximal subcluster
      reduces both gene expression and histone acetylation throughout the approximately
      130 kb region. A similar down regulation phenotype is displayed by transactivator
      deficient cell variants, but this phenotype can be rescued by transfecting the
      cells with expression cassettes encoding hepatocyte nuclear factor-1alpha (HNF
      1alpha) or HNF-4. Taken together, these results suggest that histone acetylation
      depends on interactions between the HNF-1alpha/HNF-4 signaling cascade and the
      serpin LCR.

PMID- 15942033
TI  - Cyclophilin D: knocking on death's door.
AB  - Two recent genetic studies have identified a critical role for cyclophilin D, a
      component of the mitochondrial membrane permeability transition pore, in cell
      death induced by calcium, reactive oxygen species, and cardiac ischemia
      reperfusion injury. Transgenic mice lacking cyclophilin D developed normally but
      showed reduced infarct size after coronary artery ligation and reperfusion. Cells
      from the knockout mice were resistant to death imposed by excess calcium and
      H2O2, but not to death from x-irradiation, staurosporine, tumor necrosis factor
      alpha, or forced expression of proapoptotic proteins. These data raise questions
      about the relationship between apoptotic and necrotic cell death, and they also
      highlight cyclophilin D as a potential therapeutic target in myocardial
      infarction.

PMID- 15942034
TI  - Biosolid colloid-mediated transport of copper, zinc, and lead in waste-amended
      soils.
AB  - Increasing land applications of biosolid wastes as soil amendments have raised
      concerns about potential toxic effects of associated metals on the environment.
      This study investigated the ability of biosolid colloids to transport metals
      associated with organic waste amendments through subsurface soil environments
      with leaching experiments involving undisturbed soil monoliths. Biosolid colloids
      were fractionated from a lime-stabilized, an aerobically digested, and a poultry
      manure organic waste and applied onto the monoliths at a rate of 0.7 cm/h.
      Eluents were monitored for Cu, Zn, Pb, and colloid concentrations over 16 to 24
      pore volumes of leaching. Mass-balance calculations indicated significantly
      higher (up to 77 times) metal elutions in association with the biosolid colloids
      in both total and soluble fractions over the control treatments. Eluted metal
      loads varied with metal, colloid, and soil type, following the sequences Zn = Cu
      > Pb, and ADB > PMB > LSB colloids. Colloid and metal elution was enhanced by
      decreasing pH and colloid size, and increasing soil macroporosity and organic
      matter content. Breakthrough curves were mostly irregular, showing several maxima
      and minima as a result of preferential macropore flow and multiple clogging and
      flushing cycles. Soil- and colloid-metal sorption affinities were not reliable
      predictors of metal attenuation/elution loads, underscoring the dynamic nature of
      transport processes. The findings demonstrate the important role of biosolid
      colloids as contaminant carriers and the significant risk they pose, if
      unaccounted, for soil and ground water contamination in areas receiving heavy
      applications of biosolid waste amendments.

PMID- 15942035
TI  - Distribution and speciation of metals in annual rings of black willow.
AB  - Information on the spatial distribution and speciation of metals in
      nonhyperaccumulator plants is lacking. This study used synchrotron X-ray
      fluorescence (SXRF) compositional imaging to investigate the spatial distribution
      of Ni, Mn, Cu, Zn, and Fe in annual rings of black willow (Salix nigra L.)
      collected from a metal-contaminated area, and used X-ray absorption spectroscopy
      (XAS) to investigate Ni and Mn speciation in regions of the annual rings with
      elevated Ni concentrations. Annual rings were recollected in early 2003 from an
      individual known to be enriched with Ni from previous studies. Compositional
      imaging showed Ni and associated co-contaminants conservatively located in an
      annual ring. When compared with a corresponding photomicrograph, SXRF
      compositional images showed that metals were sharply constrained by the
      boundaries of the annual ring, indicating a sudden onset and cessation of uptake,
      and a lack of post-growth mobility of the metals. There was a particularly strong
      correlation between Ni and Mn in the metal-enriched annual ring (r = 0.8822),
      which suggested similar transport and binding behavior of these elements. X-ray
      absorption spectroscopy showed Ni and Mn to be present in the 2+ oxidation state.
      X-ray absorption near edge structure spectroscopy (XANES) fingerprinting of
      localized, highly Ni-enriched regions within the lumen of willow xylem vessels
      found similarities with Ni-pectic acid complexes, Ni-histidine, and NiSO4.

PMID- 15942036
TI  - Stochastic modeling of diffuse pesticide losses from a small agricultural
      catchment.
AB  - The objective of this study was to identify the main sources of variation in
      pesticide losses at field and catchment scales using the dual permeability model
      MACRO. Stochastic simulations of the leaching of the herbicide MCPA (4-chloro-2
      methylphenoxyacetic acid) were compared with seven years of measured
      concentrations in a stream draining a small agricultural catchment and one year
      of measured concentrations at the outlet of a field located within the catchment.
      MACRO was parameterized from measured probability distributions accounting for
      spatial variability of soil properties and local pedotransfer functions derived
      from information gathered in field- and catchment-scale soil surveys. At the
      field scale, a single deterministic simulation using the means of the input
      distributions was also performed. The deterministic run failed to reproduce the
      summer outflows when most leaching occurred, and greatly underestimated pesticide
      leaching. In contrast, the stochastic simulations successfully predicted the
      hydrologic response of the field and catchment and there was a good resemblance
      between the simulations and measured MCPA concentrations at the field outlet. At
      the catchment scale, the stochastic approach underestimated the concentrations of
      MCPA in the stream, probably mostly due to point sources, but perhaps also
      because the distributions used for the input variables did not accurately reflect
      conditions in the catchment. Sensitivity analyses showed that the most important
      factors affecting MACRO modeled diffuse MCPA losses from this catchment were soil
      properties controlling macropore flow, precipitation following application, and
      organic carbon content.

PMID- 15942037
TI  - Residues of endosulfan and other selected organochlorine pesticides in farm areas
      of the Lower Fraser Valley, British Columbia, Canada.
AB  - Crop soils, ditch sediments, and water flowing from several farm areas to salmon
      tributary streams of the Fraser River in the Lower Fraser Valley (LFV) of British
      Columbia, Canada, were sampled in 2002-2003 to quantify for residues of an
      organochlorine cyclodiene pesticide, endosulfan (END = alpha-endosulfan + beta
      endosulfan + endosulfan sulfate). Residues from historical use of other selected
      organochlorine pesticides, namely, cyclodienes (aldrin, alpha-chlordane, gamma
      chlordane, dieldrin, endrin, endrin aldehyde, heptachlor, and heptachlor
      epoxide), hexachlorocyclohexanes [alpha-benzene-hexachloride (alpha-BHC), beta
      BHC, delta-BHC, and gamma-BHC (lindane)], and DDT-related compounds (p,p-DDT, p,p
      DDD, p,p-DDE, and methoxychlor) were also determined. Reference and background
      levels of these pesticides in ditches leading to fish streams were obtained from
      pristine watershed areas. Varying amounts of END residues were detected in soils
      (<0.02-5.60 mg kg(-1) dry wt.) and ditch sediments (<0.02-3.33 mg kg(-1) dry wt.)
      in mainly three of five farm areas sampled. Likewise, residues (excluding END) of
      other selected organochlorine compounds such as aldrin, BHC, chlordane, endrin,
      p,p-DDT, methoxychlor, and their respective major transformation products
      (endosulfan sulfate, dieldrin, endrin aldehyde, heptachlor, heptachlor epoxide,
      p,p-DDD, and p,p-DDE) were found in crop soils (<0.02-16.2 mg kg(-1) dry wt.) and
      sediments (<0.02-9.73 mg kg(-1) dry wt.). Most of these pesticides (END: <0.01
      1.86 microg L(-1); other selected organochlorine pesticides: <0.0.1-1.50 microg
      L(-1)) were also found in ditch water leading to salmon streams in several farms.
      The END levels of crop soils from the same LFV study farms in 1994 and 2003
      indicated an estimated decline of 22% to 1.35 mg kg(-1) dry wt. during that
      period. This reduction was probably due to the increasing use of alternate
      pesticides (e.g., organophosphorus compounds). Some possible biological
      implications of these pesticide residues on nontarget organisms in the LFV are
      discussed.

PMID- 15942038
TI  - A new way to use solid-state carbon-13 nuclear magnetic resonance spectroscopy to
      study the sorption of organic compounds to soil organic matter.
AB  - Several solid-state 13C nuclear magnetic resonance (NMR) techniques were used to
      characterize soil organic matter spiked with 13C-labeled organic compounds
      spanning a range of hydrophobicities (benzoic acid, benzophenone, naphthalene,
      phenanthrene, and palmitic acid). The chemical shifts of NMR resonances of the
      sorbed species were shifted by up to 3 ppm relative to those of the neat
      compounds. Sorption also resulted in increased resonance linewidth for the
      compounds containing a single 13C label, indicating the presence of a range of
      different chemical environments at the sites of sorption. On the other hand,
      sorption decreased the linewidth of the resonance of naphthalene, which was
      uniformly 13C-labeled. This was attributed to the removal of intermolecular 13C
      13C dipolar coupling. Heterogeneity of the organic matter was demonstrated using
      the spectral editing technique proton spin relaxation editing (PSRE), which
      enabled the identification and quantification of charcoal-rich domains
      characterized by rapid rates of proton spin-lattice relaxation in the static
      frame (T1H), and humic domains characterized by slow rates of T1H relaxation.
      Furthermore it was demonstrated that the sorbed 13C-labeled molecules "inherit"
      the T1H "signature" of the organic matrix in their immediate vicinity. Thus PSRE
      on the spiked soils enabled evaluation of the relative affinity of the two domain
      types for the sorbate molecules. The charcoal-rich domains were shown to have a
      twofold to tenfold greater affinity for the organic compounds, with greater
      differences found for the more hydrophobic compounds.

PMID- 15942039
TI  - Accelerated soil dissipation of tebuconazole following multiple applications to
      peanut.
AB  - Repeated application may increase rates of pesticide dissipation in soil and
      reduce persistence. The potential for this to occur was investigated for the
      fungicide, tebuconazole (alpha-[2-(4-chlorophenyl)ethyl]-alpha-(1,1
      dimethylethyl)-1H-1,2,4-triazole-1-ethanol), when used for peanut (Arachis
      hypogaea L.) production. Soil samples were collected from peanut plots after each
      of four tebuconazole applications at 2-wk intervals. Soil moisture was adjusted
      to field capacity as necessary and samples were incubated in the laboratory for
      63 d at 30 degrees C. Untreated plot samples spiked with the compound served as
      controls. Results indicated accelerated dissipation in field-treated samples with
      the time to fifty percent dissipation (DT50) decreasing from 43 to 5 d after
      three tebuconazole applications. Corresponding increases in rates of accumulation
      and decay of degradates were also indicated. Best-fit equations (r2 = 0.84-0.98)
      to dissipation kinetic data combined with estimates of canopy interception rates
      were used to predict tebuconazole and degradates concentration in soil after each
      successive application. Predicted concentrations compared with values measured in
      surface soil samples were from twofold less to twofold greater. Use of kinetic
      data will likely enhance assessments of treatment efficacy and human and
      ecological risks from normal agronomic use of tebuconazole on peanut. However,
      the study indicated that varying soil conditions (in particular, soil temperature
      and water content) may have an equal or greater impact on field dissipation rate
      than development of accelerated dissipation. Results emphasize that extension of
      laboratory-derived kinetic data to field settings should be done with caution.

PMID- 15942040
TI  - Phosphorus in Hawaiian kikuyugrass pastures and potential phosphorus release to
      water.
AB  - Pasture systems in Hawaii are based primarily on kikuyugrass (Pennisetum
      clandestinum Hochst. ex Chiov.). Relationships among kikuyugrass P concentration,
      animal P requirements, and various soil P determinations are needed to help
      identify source areas for implementing pasture management strategies to limit P
      loss via overland flow. A total of 51 rotationally stocked kikuyugrass pastures
      (>20 yr old) with contrasting soil chemical properties were sampled. A
      satisfactory predictive relationship between modified-Truog (MT)-extractable
      phosphorus (P(MT)) and dissolved (<0.45-mum pore diameter), molybdate-reactive
      phosphorus (DRP) desorbed from soil in a water extract (DRP(WE)) was found when 0
      to 4-cm-depth data for the soil orders with medium to high DRP(WE) (two
      Mollisols and an Inceptisol) were pooled separately from those with low DRP(WE)
      (five Andisols, three Ultisols, and an Oxisol). The oxalate phosphorus saturation
      index (PSI(ox)) procedure was the best predictor of DRP(WE) across soil orders
      when oxalate-extractable molybdate-reactive phosphorus (RP(ox)) was used to
      calculate PSI(ox) (PSI(ox)RP) rather than when total oxalate-extractable
      phosphorus (TP(ox)) was used (PSI(ox)TP). There was little DRP(WE) until
      PSI(ox)RP exceeded 6% or PSI(ox)TP exceeded 8%. A more empirical dilute-acid
      phosphorus saturation index (PSI(MT)) was also calculated using P(MT) and MT
      extractable iron (Fe(MT)) and aluminum (Al(MT)). The PSI(MT) procedure showed
      some utility in predicting DRP(WE), was positively related to the PSI(ox)
      procedures, and can be more readily performed in agronomic soil testing
      laboratories than PSI(ox). The present research suggests that while Hawaiian
      kikuyugrass pastures tend to be sufficient to high in forage P, potential soil P
      release to water only appeared to be a possible environmental concern for the
      Mollisol and Inceptisol sites.

PMID- 15942041
TI  - Phosphorus concentrations in overland flow from diverse locations on a New York
      dairy farm.
AB  - The National Phosphorus Project rainfall simulator was used to quantify overland
      flow and P transport from nine sites distributed throughout the watershed of a
      New York City Watershed Agriculture Program collaborating dairy farm. Observed
      concentrations of total dissolved phosphorus (TDP) were low (0.007-0.12 mg L(-1))
      in flow from deciduous forest, extensively managed pasture, and hillside seeps;
      moderate (0.18-0.64 mg L(-1)) in flow from intensively managed pastures, a
      hayfield, and a cow path; and extremely high (11.6 mg L(-1)) in flow from a
      manured barnyard. Concentrations of TDP from sites without fresh manure were
      strongly correlated with soil test P (TDP [mg L(-1)] = 0.0056 + 0.0180 x Morgan's
      soil test phosphorus [STP, mg kg(-1)]; R2 = 84%). Observed concentrations of
      suspended solids were low (16-137 mg L(-1)) in flow from vegetated sites, but
      were higher (375-615 mg L(-1)) in flow from sites with little ground cover
      (barnyard, cow path, plowed field). Under dry summer conditions the time to
      observed overland flow was shorter (<18 min) for nonfield areas (seeps, barnyard,
      cow path) than for field and forest areas (27-93 min), indicating that
      hydrologically active nonfield areas of minor spatial extent but with high soil P
      (e.g., cow paths and barnyards) can play a significant role in summertime P
      loading. When soils started from field capacity (second-day) time to overland
      flow was uniformly less than 23 min, indicating that under wet watershed
      conditions low-P source areas can dilute overland flow from concentrated sources.

PMID- 15942042
TI  - Movement of lagoon-liquor constituents below four animal-waste lagoons.
AB  - Movement of liquor constituents from animal-waste lagoons has the potential to
      degrade ground water quality. The depth of movement and concentrations of lagoon
      liquor constituents in the soil underlying three cattle (Bos taurus)-waste
      retention lagoons and one swine (Sus scrofa)-waste lagoon were determined.
      Samples were taken by using a direct-push coring machine, dissected by depth, and
      analyzed for total N, organic C, CaCO3, pH, cation exchange capacity (CEC),
      texture, and extractable NO3, NH(4), P, Cl, Ca, Mg, K, and Na. Ammonium N
      concentrations were greatest in the upper 0.5 m of soil under all four lagoons
      with concentrations ranging from 94 to 1139 mg kg(-1). Organic N was determined
      to make up between 39 and 74% of the total N beneath all lagoons. The swine
      lagoon had 2.4 kg N m(-2) in the underlying soil whereas the cattle lagoon with
      highest quantity of N had 1.2 kg N m(-2) in the underlying soil. Although N
      concentrations decreased with depth, N was greater than expected background
      levels at the bottom of some cores, indicating that the sampling efforts did not
      reach the bottom of the N plume. Nitrate N concentrations were generally less
      than 5 mg kg(-1) immediately below the lagoon floor. In the uppermost 0.5 m of
      soil underlying the swine and three cattle lagoons, NH4+ occupied 44% and between
      1 and 22% of the soil cation exchange sites, respectively. The depth of movement
      of N under these lagoons, as much as 4 m, may pose remediation difficulties at
      lagoon closure.

PMID- 15942043
TI  - Phosphorus leaching at cold temperatures as affected by wastewater application
      and soil phosphorus levels.
AB  - Land application of wastewater in the northern-tier United States during winter
      months has been suggested as a means to reduce cost of building storage lagoons.
      A study was initiated in 1996 to assess land application of potato-processing
      wastewater on a 120-ha field at Park Rapids, MN. One objective of this study was
      to evaluate the effects of soil P levels and temperature on P leaching in soil
      columns. In this paper, we report the P sorption, desorption, and leaching
      characteristics of a high-P (>200 mg kg(-1)) and a low-P (<25 mg kg(-1)) surface
      soil from the wastewater irrigation site. The leaching experiment was done with
      wastewater at 4 +/- 2 or 10 +/- 2 degrees C. The high-P soil resulted in an
      equilibrium P concentration of 8.0 mg L(-1) compared with 0.14 mg L(-1) for the
      low-P soil. When low-P wastewater was applied to the high-P soil, the soil acted
      as a P source, and the total phosphorus (TP) concentration in the leachate was
      3.5 times higher than the input TP concentration (C0). When high-P wastewater was
      applied to the high-P soil, the soil acted as a P sink retarding the TP
      concentration in the leachate by 80%. Phosphorus desorption was higher at 10
      degrees C compared with 4 degrees C. The results showed that depending on P
      levels of the soil and the wastewater, reduction or increase in leachate P will
      occur below the surface soil. However, further mobility of this P under field
      conditions will depend on the volume and rate of percolating water as well as the
      sorption-desorption characteristics of the subsoil.

PMID- 15942044
TI  - Phosphorus retention in small constructed wetlands treating agricultural drainage
      water.
AB  - The construction of artificial wetlands has become a measure increasingly applied
      to reduce nonpoint-source (NPS) pollution and to contribute to the restoration of
      eutrophic lakes and coastal waters. In a 2-yr study monitoring fluxes of
      particulate and dissolved phosphorus (P) in a small artificial wetland for the
      treatment of agricultural drainage water in Central Switzerland, water residence
      time was identified as the main factor controlling P retention in the system.
      Since most of the annual P load (62% as dissolved reactive phosphorus, DRP) was
      related to high discharge events, it was not average but minimum water residence
      time during flood events that determined the wetland's P retention. In agreement
      with a continuous stirred tank reactor (CSTR) model, our investigations suggest a
      minimum water residence time of 7 d to retain at least 50% of the bioavailable P.
      The investigated wetland retained only 2% of the bioavailable P, since the water
      residence time was shorter than 7 d during 61% of time in both years. Settling of
      phytoplankton rather than DRP uptake into phytoplankton limited the retention of
      bioavailable P. The overall retention efficiency of 23% total phosphorus (TP),
      corresponding to a surface related retention of 1.1 g P m(-2) yr(-1), was due to
      the efficient trapping of pedogenic particles.

PMID- 15942045
TI  - Glomerular abundance of nephrin and podocin in experimental nephrotic syndrome:
      different effects of antiproteinuric therapies.
AB  - Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria,
      hypoalbuminemia, and eventual edema formation. Although the mechanisms underlying
      this phenomenon are not yet fully clarified, it is well accepted that nephrin and
      podocin are involved in the development of proteinuria. The effects of early
      treatment with various antiproteinuric therapies on proteinuria and glomerular
      staining of nephrin and podocin in rats with experimental NS have not been
      previously studied. Proteinuria and glomerular nephrin and podocin
      immunofluorescence were examined in rat kidneys with adriamycin-induced NS and
      the effects of antiproteinuric drug therapies during 5 wk with enalapril,
      losartan, alone or in combination, omapatrilat, and mycophenolate mofetil on
      these parameters were assessed. Injection of adriamycin caused a significant
      increase in daily (from 21.8 +/- 1.4 to 983.1 +/- 45.8 mg/day, P < 0.01) and
      cumulative protein excretion (from negligible values to 22,490 +/- 931 mg, P <
      0.001) during 5 wk. Early treatment with enalapril significantly decreased the
      daily (641.7 +/- 82.4 mg/day, P < 0.0023) and cumulative proteinuria (15,727 +/-
      2,204 mg, P < 0.001). A similar effect, although to a lesser extent, was obtained
      after omapatrilat treatment: cumulative proteinuria was reduced to 18,706 +/-
      1,042 mg, P < 0.001. In contrast, losartan treatment did not significantly
      influence the cumulative proteinuria that remained comparable (20,351 +/- 1,360
      mg, P > 0.05) to that observed in untreated NS rats. Unexpectedly, when losartan
      was given in combination with enalapril, it abolished the beneficial effects of
      the latter. Pretreatment with mycophenolate mofetil exerted a moderate
      antiproteinuric effect, which appeared only during the last week of the
      experimental treatment. Nephrotic rats exhibited severe disruption of slit
      diaphragm structure as seen by rapid and profound loss of nephrin and podocin.
      Beneficial effects of enalapril, omapatrilat, and mycophenolate mofetil
      paralleled the preservation of nephrin, as determined immunohistochemically, and
      enabled prediction of significant antiproteinuric responses. Enalapril alone or
      in combination with losartan resulted in significant preservation of podocin.
      Pretreatment with enalapril, and to a lesser extent omapatrilat, is superior to
      losartan in reducing proteinuria in NS rats. A combination of ACE inhibitors with
      ANG II receptor blockers does not provide any advantageous antiproteinuric
      therapy in these animals. Nephrin loss is an indication of proteinuria in NS and
      the antiproteinuric effects of ACE inhibitors, vasopeptidase inhibitors, and
      mycophenolate mofetil attenuate this reduction. Not all the drugs which restore
      podocin reduce urinary protein in NS.

PMID- 15942046
TI  - Glucocorticoids acutely increase cell surface Na+/H+ exchanger-3 (NHE3) by
      activation of NHE3 exocytosis.
AB  - Glucocorticoids have important effects on renal function, including the
      modulation of renal acidification by the major proximal tubular Na(+)/H(+)
      exchanger, NHE3. While the chronic effect of glucocorticoids is considered to be
      primarily at the transcriptional level, with increases in NHE3 mRNA and protein
      expression driving increased transport activity, the mechanisms by which
      glucocorticoids activate NHE3 in an acute setting have not been investigated.
      Previous studies have shown that a glucocorticoid-stimulated increase in NHE3
      activity can occur before any detectable change in NHE3 mRNA. The present study
      examines the acute effects of glucocorticoids on NHE3 using opossum kidney (OKP)
      cells as a cell model. In OKP cells, total NHE3 protein abundance was not changed
      by 3 h of treatment with dexamethasone (10(-6) M). However, the biotin-accessible
      fraction representing NHE3 at the apical membrane as well as Na(+)/H(+) exchange
      activity measured fluorimetrically using the pH-sensitive dye BCECF-AM were
      significantly increased. These effects were not prevented by the protein
      synthesis inhibitor cycloheximide. NHE3 insertion (biotinylatable NHE3 after
      sulfo-NHS-acetate blockade) was stimulated by dexamethasone incubation, with or
      without cycloheximide. The rate of NHE3 endocytic retrieval, assessed either by
      the avidin protection assay (early endocytosis) or by the sodium 2-mercaptoethane
      sulfonate (MesNa) cleavage assay (early and late endocytosis), was not affected
      by dexamethasone. These findings suggest that trafficking plays a key role in the
      acute stimulation of NHE3 by glucocorticoids, with exocytosis being the major
      contributor to the glucocorticoid-induced rapid increase in cell surface NHE3
      protein abundance and Na(+)/H(+) exchange activity.

PMID- 15942048
TI  - Zinc protects renal function during cadmium intoxication in the rat.
AB  - This study investigates the effect in the rat of chronic CdCl2 intoxication (500
      microg Cd2+/kg, daily i.p. injection for 5 days) on renal function and the
      changes in tight junction proteins claudin-2, claudin-3, and claudin-5 present in
      rat kidney. We also studied the effect of coadministration of ZnCl2 (500 microg
      Zn2+/kg) during chronic CdCl2 intoxication. Our results indicate that 1) most of
      the filtered Cd2+ is reabsorbed within the kidney; 2) chronic Cd2+ intoxication
      can induce a change in renal handling of ions without altering glomerular
      filtration rate; 3) a delayed nephropathy, showing Fanconi-like features, appears
      more than 5 days after the end of CdCl2 exposure; 4) epithelial integrity is
      altered by chronic Cd2+ intoxication affecting the expression and localization of
      claudin tight junction proteins; and 5) cotreatment with Zn2+ protects against
      the renal toxic effects of Cd2+, preventing altered claudin expression and
      inhibiting apoptosis. In conclusion, these results show that Cd2+ toxicity and
      cellular toxic mechanisms are complex, probably affecting both membrane
      transporters and tight junction proteins. Finally, Zn2+ supplementation may
      provide a basis for future treatments.

PMID- 15942047
TI  - Calcium and chloride channel activation by angiotensin II-AT1 receptors in
      preglomerular vascular smooth muscle cells.
AB  - The pathways responsible for the rapid and sustained increases in [Ca(2+)](i)
      following activation of ANG II receptors (AT(1)) in renal vascular smooth muscle
      cells were evaluated using fluorescence microscopy. Resting intracellular calcium
      concentration [Ca(2+)](i) averaged 75 +/- 9 nM. The response to ANG II (100 nM)
      was characterized by a rapid initial increase of [Ca(2+)](i) by 74 +/- 6 nM (n =
      35) followed by a decrease to a sustained level of 12 +/- 2 nM above baseline.
      The average time from peak to 50% reduction from the peak value (50% time point)
      was 32 +/- 4 s. AT(1) receptor blockade with 1 microM candesartan (n = 5)
      prevented the responses to ANG II. In nominally calcium-free conditions (n = 8),
      the peak increase in [Ca(2+)](i) averaged 42 +/- 7 nM but the sustained phase was
      absent and the 50% time point was reduced to 11 +/- 4 s. L-type calcium channel
      blockade with diltiazem reduced the peak [Ca(2+)](i) to 24 +/- 8 nM and the
      sustained level to 4 +/- 2 nM (n = 10). In cells preincubated in low Cl(-) (3.0
      mM), the peak response to ANG II was suppressed as was the sustained response.
      Blockade of chloride channels with DIDS eliminated both the peak and sustained
      responses (n = 11); chloride channel blockade with DPC (n = 17) suppressed the
      peak increase in [Ca(2+)](i) to 18 +/- 5 and also prevented the sustained
      response. IP3 receptor blockade by 10 microM TMB-8 (n = 6) reduced the peak to 22
      +/- 8 and prevented the sustained response. Exposure to 10 microM TMB-8 in the
      presence of Ca(2+)-free medium prevented the ANG II response (n = 9). In the
      presence of 100 microM DPC and 10 microM TMB-8 (n = 7), the ANG II response was
      also prevented. Thus the rapid initial increase in [Ca(2+)](i) is due not only to
      release from intracellular stores, but also to Ca(2+) influx from the
      extracellular fluid. Although Ca(2+) entry via L-type calcium channels is
      responsible for the major portion of the sustained response, other entry pathways
      participate. The finding that chloride channel blockers markedly attenuate both
      rapid and sustained responses indicates that chloride channel activation
      contributes to, rather than being the consequence of, the initial rapid response.

PMID- 15942049
TI  - Angiotensin II, reactive oxygen species, and Ca2+ signaling in afferent
      arterioles.
AB  - In afferent arteriolar vascular smooth muscle cells, ANG II induces a rise in
      cytosolic Ca(2+) ([Ca(2+)](i)) via inositol trisphosphate receptor (IP(3)R)
      stimulation and by activation of the adenine diphosphate ribose (ADPR) cyclase to
      form cyclic ADPR, which sensitizes the ryanodine receptor (RyR) to Ca(2+). We
      hypothesize that ANG II stimulation of NAD(P)H oxidases leads to the formation of
      superoxide anion (O(2)-*, which, in turn, activates ADPR cyclase. Afferent
      arterioles were isolated from rat kidney with the magnetized microsphere and
      sieving technique and loaded with fura-2 to measure [Ca(2+)](i). ANG II rapidly
      increased [Ca(2+)](i) by 124 +/- 12 nM. In the presence of apocynin, a specific
      inhibitor of NAD(P)H oxidase assembly, the [Ca(2+)](i) response was reduced to 35
      +/- 5 nM (P < 0.01). Tempol, a superoxide dismutase mimetic, did not alter the
      [Ca(2+)](i) response to ANG II at a concentration of 10(-4) M (99 +/- 12 nM), but
      10(-3) M tempol reduced the response to 32 +/- 3 nM (P < 0.01). The addition of
      nicotinamide, an inhibitor of ADPR cyclase, to apocynin or tempol (10(-3) M)
      resulted in no further inhibition. Measurement of superoxide production with the
      fluorescent probe tempo 9-AC showed that ANG II caused an increase of 48 +/- 20
      arbitrary units; apocynin or diphenyl iodonium (an inhibitor of flavoprotein
      oxidases) inhibited the response by 94%. Hydrogen peroxide (H(2)O(2)) was studied
      at physiological (10(-7) M) and higher concentrations. In the presence of
      H(2)O(2) (10(-7) M), neither baseline [Ca(2+)](i) nor the response to ANG II was
      altered (125 +/- 15 nM), whereas H(2)O(2) (10(-6) and 10(-5) M) inhibited the
      [Ca(2+)](i) response to ANG II by 35 and 46%, respectively. We conclude that ANG
      II rapidly activates NAD(P)H oxidases of afferent arterioles, leading to the
      formation of O(2)-*, which then stimulates ADPR cyclase to form cADPR. cADPR, by
      sensitizing the RyR to Ca(2+), augments the Ca(2+) response (calcium-induced
      calcium release) initiated by activation of the IP(3)R.

PMID- 15942050
TI  - Oxygen availability limits renal NADPH-dependent superoxide production.
AB  - Renal oxygen tension is substantially lower in the medulla than in the cortex and
      is reduced in hypertensive rats, a model of oxidative stress. Expression of NADPH
      oxidase, the primary source for superoxide anion (O(2)(-)*) in the kidney, is
      elevated in hypertension. Because molecular oxygen (O(2)) is required for O(2)(
      )* formation, we tested the hypothesis that renal NADPH oxidase activity is
      limited by low O(2). O(2)(-)* production by rat kidney tissue or cultured cells
      exposed to levels of Po(2) that mimics those in the kidney was assessed by
      lucigenin-enhanced chemiluminescence. NADPH-dependent O(2)(-)* production by
      kidney homogenates decreased reversibly by 60-90% after graded reductions of
      ambient O(2) from 10 to 0% (76 to 2 mmHg Po(2)). The NADPH-dependent O(2)(-)*
      production by the kidney homogenate was reduced by decreasing Po(2) below
      approximately 30 mmHg. The response of tissue homogenates to low Po(2) was not
      different between normotensive and hypertensive rats. Similarly, NADPH-dependent
      O(2)(-)* production was lower during 2% O(2) compared with 10% O(2) in rat
      proximal tubule cells (-57 +/- 1%), vascular smooth muscle (-42 +/- 5%),
      cardiomyocytes (-57 +/- 1%), and mouse inner medulla collecting duct cells (-58
      +/- 3%). We conclude that O(2)(-)* production by NADPH oxidase is dependent on
      availability of O(2). Therefore, O(2)(-)* generation may be limited in the
      kidney, both in the normal renal medulla and in the cortex of hypertensive
      kidneys.

PMID- 15942051
TI  - Meprin-alpha in chronic diabetic nephropathy: interaction with the renin
      angiotensin axis.
AB  - Meprin (MEP) A is a metalloendopeptidase that is present in the renal proximal
      tubule brush-border membrane (BBM) and that colocalizes with angiotensin
      converting enzyme (ACE). The MEP beta-chain gene locus on chromosome 18 has been
      linked to a heightened risk of diabetic nephropathy (DN) in patients with type 2
      diabetes. This study evaluated 1) whether MEP-alpha and MEP-beta gene and protein
      expression are altered in db/db mice before the onset of DN and 2) the role of
      MEP-alpha in the pathogenesis of DN and the impact of the renin-angiotensin
      system on this interaction in two experimental models of diabetes. MEP-alpha and
      MEP-beta gene and protein expression were evaluated in db/db mice, 13-14 wk of
      age, compared with lean C57BLKS/J littermate animals. A treatment study was then
      performed in which db/db mice and controls were assigned to one of three groups:
      control (C) water, no therapy; ACE inhibitor therapy, enalapril (EN)-treated
      water, 50 mg/l; ANG II receptor type 1 blocker (ARB) therapy, losartan (LOS)
      treated water, 500 mg/l. Treatment was started at 8 wk of age and continued for
      52 wk. Male Sprague-Dawley rats with diabetes for 52 wk following a single dose
      of streptozocin (STZ; 60 mg/kg) were also studied. At 13.5 wk of age, MEP-alpha
      and MEP-beta kidney mRNA abundance and protein expression were significantly
      lower in db/db mice compared with lean controls, with greater changes in MEP-beta
      (P < 0.05). In the treatment study, EN ameliorated and LOS exacerbated DN in
      db/db mice. BBM MEP A enzymatic activity and MEP-alpha protein content were lower
      in db/db mice vs. control nonobese mice at 52 wk (P < 0.02). EN-treated db/db
      mice showed increased MEP A activity, MEP-alpha content in BBM, decreased urinary
      MEP-alpha excretion, and enhanced BBM staining for MEP-alpha protein vs. C and
      LOS-treated db/db mice. In nonobese mice, EN and LOS treatment had no effect on
      MEP-alpha expression. In rats with STZ-induced diabetes for 52 wk, urinary MEP
      alpha excretion was increased and MEP A activity and MEP-alpha protein content
      per milligram of BBM protein were decreased compared with age-matched control
      animals (P < 0.05). These results indicate that db/db mice manifest decreased MEP
      alpha and MEP-beta gene and protein expression, before the development of overt
      kidney disease. Moreover, in db/db mice with DN and rats with STZ-diabetes, there
      was an inverse relationship between renal MEP-alpha content and the severity of
      the renal injury. Treatment with an ACE inhibitor was more effective than ARB in
      ameliorating DN in db/db mice, a change that correlated with alterations in
      urinary excretion and BBM content of MEP-alpha. MEP-alpha may play a role in the
      pathogenesis of DN and the benefits of ACE inhibitor therapy on the progression
      of diabetic kidney disease may be related, in part, to its impact on renal MEP
      alpha expression.

PMID- 15942052
TI  - ClC-5: role in endocytosis in the proximal tubule.
AB  - The proper functioning of the Cl(-) channel, ClC-5, is essential for the uptake
      of low molecular mass proteins through receptor-mediated endocytosis in the
      proximal tubule. Dent's disease patients with mutant ClC-5 channels and ClC-5
      knockout (KO) mice both have low molecular mass proteinuria. To further
      understand the function of ClC-5, endocytosis was studied in LLC-PK(1) cells and
      primary cultures of proximal tubule cells from wild-type (WT) and ClC-5 KO
      kidneys. Endocytosis in the proximal tubule cells from KO mice was reduced
      compared with that in WT animals. Endocytosis in WT but not in KO cells was
      inhibited by bafilomycin A-1 and Cl(-) depletion, whereas endocytosis in both WT
      and KO cells was inhibited by the NHE3 blocker, S3226. Infection with adenovirus
      containing WT ClC-5 rescued receptor-mediated endocytosis in KO cells, whereas
      infection with any of the three disease-causing mutants, myc-W22G-ClC-5, myc
      S520P-ClC-5, or myc-R704X-ClC-5, did not. WT and the three mutants all trafficked
      to the apical surface, as assessed by surface biotinylation. WT-ClC-5 and the
      W22G mutant were internalized similarly, whereas neither the S520P nor the R704X
      mutants was. These data indicate that ClC-5 is important for Cl(-) and proton
      pump-mediated endocytosis. However, not all receptor-mediated endocytosis in the
      proximal tubule is dependent on ClC-5. There is a significant fraction that can
      be inhibited by an NHE3 blocker. Our data from the mutants suggest that defective
      targeting and trafficking of mutant ClC-5 to the endosomes are a major
      determinant in the lack of normal endocytosis in Dent's disease.

PMID- 15942053
TI  - Defective PTH regulation of sodium-dependent phosphate transport in NHERF-1-/-
      renal proximal tubule cells and wild-type cells adapted to low-phosphate media.
AB  - The present experiments using primary cultures from renal proximal tubule cells
      examine two aspects of the regulation of sodium-dependent phosphate transport and
      membrane sodium-dependent phosphate transporter (Npt2a) expression by parathyroid
      hormone (PTH). Sodium-dependent phosphate transport in proximal tubule cells from
      wild-type mice grown in normal-phosphate media averaged 4.4 +/- 0.5 nmol.mg
      protein(-1).10 min(-1) and was inhibited by 30.5 +/- 8.6% by PTH (10(-7) M). This
      was associated with a 32.7 +/- 5.2% decrease in Npt2a expression in the plasma
      membrane. Proximal tubule cells from Na(+)/H(+) exchanger regulatory factor-1
      (NHERF-1)(-/-) mice had a lower rate of phosphate transport compared with wild
      type cells and a significantly reduced inhibitory response to PTH. Wild-type
      cells incubated in low-phosphate media for 24 h had a higher rate of phosphate
      transport compared with wild-type cells grown in normal-phosphate media but a
      significantly blunted inhibitory response to PTH. These data indicate a role for
      NHERF-1 in mediating the membrane retrieval of Npt2a and the subsequent
      inhibition of phosphate transport in renal proximal tubules. These studies also
      suggest that there is a blunted phosphaturic effect of PTH in cells adapted to
      low-phosphate media.

PMID- 15942054
TI  - Progress in assessing the public health impact from residues of nuclear bomb
      testing in Kazakhstan.

PMID- 15942055
TI  - Issues associated with legacy contamination from past activities.

PMID- 15942056
TI  - A review of the potential for radium from luminising activities to migrate in the
      environment.
AB  - During the first half of the twentieth century, radium, mixed with other
      components, was used to luminise many items, including watches, clocks, dials and
      meters. On many sites, and in particular MoD sites, luminised instruments and
      paint were disposed of by burning and burial. This paper presents a review of the
      potential for radium from such sites to migrate in the environment. The most
      likely mechanisms of migration of radium from former luminising sites in the UK
      are surface-water erosion and transport, and the action of animals and people.
      Plant uptake or rainsplash followed by cropping of the plants is another possible
      mechanism, but the extent of impact is uncertain. The migration of significant
      quantities of radium through soils or rocks, or due to landsliding or wind
      transport, is considered to be of minimal importance to most UK sites. A low pH,
      high salinity (in particular of group II metals) or reducing groundwater would
      need to be present for migration through soils/rocks to occur and such conditions
      are unlikely to be present in most shallow aquifer systems in the UK. To reduce
      the potential for migration to occur it is recommended that luminising wastes at
      ground surface are removed or covered, that controls are put in place to limit
      animal activity and that human entry to former luminising sites is restricted.

PMID- 15942057
TI  - Tritium in well waters, streams and atomic lakes in the East Kazakhstan Oblast of
      the Semipalatinsk Nuclear Test Site.
AB  - The concentration of tritium has been determined in well waters, streams and
      atomic lakes in the Sarzhal, Tel'kem, Balapan and Degelen Mountains areas of the
      Semipalatinsk Test Site. The data show that levels of tritium in domestic well
      waters within the settlement of Sarzhal are extremely low at the present time
      with a median value of 4.4 Bq dm(-3) (95% confidence interval:4.1-4.7 Bq dm(-3)).
      These levels are only marginally above the background tritium content in surface
      waters globally. Levels in the atomic craters at Tel'kem 1 and Tel'kem 2 are
      between one and two orders of magnitude higher, while the level in Lake Balapan
      is approximately 12,600 Bq dm(-3). Significantly, levels in streams and test
      tunnel waters sourced in the Degelen Mountains, the site of approximately 215
      underground nuclear tests, are a further order of magnitude higher, being in the
      range 133,000--235,500 Bq dm(-3). No evidence was adduced which indicates that
      domestic wells in Sarzhal are contaminated by tritium-rich waters sourced in the
      Degelen massif, suggesting that the latter are not connected hydrologically to
      the near-surface groundwater recharging the Sarzhal wells. Annual doses to humans
      arising from the ingestion of tritium in these well waters are very low at the
      present time and are of no radiological significance.

PMID- 15942058
TI  - Doses from the consumption of Cardiff Bay flounder containing organically bound
      tritium.
AB  - ICRP dose coefficients for the ingestion of organically bound tritium (OBT) by
      adults and children are intended for general application to unspecified forms in
      diet and may not be applicable to intakes of a specific form of OBT. To obtain
      information relating to OBT in fish from Cardiff Bay, the retention of tritium in
      adult rats was determined after administration as either tritiated water (HTO) or
      dried flounder flesh containing OBT. Two components of retention were obtained in
      each case. The first component, attributable to tritium equilibrating with body
      water, had a half-time of retention of 3 days in each case, and accounted for 97%
      of the intake as HTO and 70% after intake of OBT in flounder. Results were
      consistent with rapid catabolism of a large proportion of flounder OBT to HTO.
      The second component of retention, attributable to OBT in rat tissues, accounted
      for 3% of tritium intake as HTO and 30% after intake as flounder OBT; the half
      times of retention were 10 days and 25 days, respectively. The results obtained
      after administration as HTO are consistent with published animal data and
      correlate with the ICRP assumptions for adult man of half-times of 10 days for
      97% behaving as HTO in body tissues and 40 days for 3% incorporated into OBT in
      body tissues. The results obtained after administration of flounder OBT suggest
      that appropriate assumptions for retention in adult man are 70% with a 10 day
      half-time and 30% with a 100 day half-time. These assumptions result in an
      ingestion dose coefficient of 6 x 10(-11) Sv Bq(-1). This compares with the ICRP
      value for OBT ingestion by adults of 4.2 x 10(-11) Sv Bq(-1), based on half-times
      of 10 days and 40 days applied to equal proportions of retained tritium. It is
      proposed that a dose coefficient of 6 x 10(-11) Sv Bq(-1) should be applied to
      tritium in flounders from Cardiff Bay. It is further proposed that this dose
      coefficient should be applied to all ingestion intakes by adults relating to this
      source of exposure, unless specific information is available showing that a
      significant proportion of the intake is HTO. The same proposals apply to dose
      coefficients derived here for flounder OBT consumption by children.

PMID- 15942059
TI  - Penetration of tritium (as tritiated water vapour) into low carbon steel and
      remediation using abrasive cleaning.
AB  - The UKAEA Winfrith site is in a phase of accelerated decommissioning and de
      licensing which will generate significant volumes of metal wastes some of which
      may be suitable for disposal as exempt wastes. If contamination is present, it is
      often confined within the surface layers of the metal. The UKAEA Winfrith site
      operates a shot-blast facility (WACM) that removes paint and surface
      contamination from low carbon steel enabling surface contaminated painted metal
      to be processed and therefore certified as exempt. A study was conducted to
      determine whether tritium (as tritiated water vapour) has penetrated into the
      metal to levels exceeding the Radioactive Substances Act (1993), Substances of
      Low Activity (SoLA) Exemption Order criteria, and whether processing via the WACM
      removes sufficient tritium contamination that the SoLA Exemption Order criteria
      can be met. The results of sampling and analysis show that the tritium is mainly
      held in the paint or outer 40 microm layer of the metal and that processing
      through the WACM removes these layers along with sufficient tritium to meet the
      SoLA Exemption Order criteria.

PMID- 15942060
TI  - Radiological safety assessment of Brazilian industrial facilities with electron
      accelerators.
AB  - Industrial electron accelerators are used by eight installations in Brazil, with
      a total of 14 machines generating electron beams. These facilities are classified
      into categories I or II, according to the International Atomic Energy Agency
      (IAEA) system. In category I are included the facilities with an integrally
      shielded unit with interlocks, where human access during operation is not
      physically possible owing to the configuration of the shielding. In category II
      are included the facilities with a unit housed in a shielded room that is kept
      inaccessible during operation by an entry control system. Of the 14 accelerators
      operational in Brazil, 11 belong to category I and three to category II. In the
      present work a methodology for the assessment of the radiological safety of these
      accelerator facilities was developed and applied, mainly on the basis of specific
      recommendations from the IAEA. The main safety items were evaluated at those
      eight installations. According to the results obtained here, no inadequacies were
      observed at the three installations in category II, from the radiological safety
      and radioprotection points of view. Nevertheless, two out of the five
      installations in category I showed several deficiencies. Most of these
      inadequacies have been corrected during this work, and the rest are in the course
      of being corrected.

PMID- 15942061
TI  - The effect of gamma irradiation on the germination and growth of certain Nigerian
      agricultural crops.
AB  - Gamma irradiation has been found to be very useful both for sterilisation in
      medicine and the preservation of food and cereals in nutrition and agriculture.
      This investigation was carried out to determine the effect of gamma irradiation
      on the subsequent germination and growth of irradiated seeds. Thirty seeds each
      of maize, okra and groundnut were irradiated to varying doses of 150, 300, 500,
      700, 900, 1000 Gy using the (60)Co gamma cell irradiator facility at the Centre
      for Energy Research and Development, Obafemi Awolowo University, Ile-Ife. These,
      as well as the controls (unirradiated seeds), were planted on the same day in an
      already prepared area of farmland during the rainy season to ensure a constant
      moisture flow. The times of germination and subsequent growth were monitored.
      Results show that maize, okra and groundnut seeds needed for planting can be
      safely stored using gamma irradiation. However, the study reveals that the number
      of germinated seeds and the growth rate for the crops decrease with increase in
      the radiation dose the seeds were exposed to. Third-degree polynomial equations
      were derived which describe the percentage germination of the crops at various
      levels of exposure. A chart of percentage germination of seeds versus exposure
      dose is also presented as a quick guide to farmers, policy makers and
      agricultural institutions.

PMID- 15942062
TI  - Investigation of photon attenuation coefficients for marble.
AB  - The total linear attenuation coefficients micro (cm(-1)) have been obtained using
      the XCOM program at photon energies of 1 keV to 1 GeV for six different natural
      marbles produced in different places in Turkey. The individual contribution of
      photon interaction processes to the total linear attenuation coefficients for
      marble has been investigated. The calculated results were also compared with the
      measurements. The results obtained for marble were also compared with concrete.

PMID- 15942063
TI  - Environmental impact of ionising radiation.

PMID- 15942066
TI  - The Chernobyl Forum: update.

PMID- 15942069
TI  - The multilevel measurement model: introduction to the special issue.
AB  - An introduction to the special issue on the multilevel measurement model (MMM) is
      provided. The two- and three-level multilevel models for continuous outcomes are
      reviewed. The extension to the hierarchical generalized linear model and its use
      as a multilevel measurement model for dichotomous measurement indicators is
      demonstrated. The six articles in the special issue are described.

PMID- 15942070
TI  - Demonstration of software programs for estimating multilevel measurement model
      parameters.
AB  - A brief overview of the relevant parameterizations of the Rasch measurement model
      will first be provided. Next, the use of five different hierarchical linear
      modeling software programs (SAS, MLWIN, S-PLUS, R and HLM) using a heuristic data
      set will be demonstrated. For each program, researchers will be offered: 1)
      instructions describing the way to set up data sets, as well as 2) directions for
      running each program, 3) guidelines to assist with the appropriate interpretation
      of the output. Last, testing of the local independence assumption will be
      discussed. All data and code for each of the models run in this analysis may be
      downloaded from the website: http://www.hlm-online.com/papers/mmmpaper.htm/.

PMID- 15942071
TI  - Mixed model estimation methods for the Rasch model.
AB  - Mixed models take the dependency between observations based on the same person
      into account by introducing one or more random effects. After introducing the
      mixed model framework, it is explained, by taking the Rasch model as a generic
      example, how item response models can be conceptualized as generalized linear and
      nonlinear mixed models. Common estimation methods for generalized linear and
      nonlinear models are discussed. In a simulation study, the performance of four
      estimation methods is assessed for the Rasch model under different conditions
      regarding the number of items and persons, and the degree of interindividual
      differences. The estimation methods included in the study are: an approximation
      of the integral over the random effect by means of Gaussian quadrature; direct
      maximization with a sixth-order Laplace approximation to the integrand; a
      linearized approximation of the nonlinear model employing PQL2; and finally a
      Bayesian MCMC method. It is concluded that the estimation methods perform almost
      equally well, except for a slightly worse recovery of the variance parameter for
      PQL2 and MCMC.

PMID- 15942072
TI  - Some links between classical and modern test theory via the two-level
      hierarchical generalized linear model.
AB  - This article considers some links between classical test theory (CTT) and modern
      test theory (MTT) such as item response theory (IRT) and the Rasch model in the
      context of the two-level hierarchical generalized linear model (HGLM).
      Conceptualizing items as nested within subjects, both the CTT model and the MTT
      model can be reformulated as an HGLM where item difficulty parameters are
      represented by fixed effects and subjects' abilities are represented by random
      effects. In this HGLM framework, the CTT and MTT models differ only in the level
      1 sampling model and the associated link function. This article also contrasts
      the Rasch and two-parameter IRT models by considering the property of specific
      objectivity in the context of CTT. It is found that the essentially tau
      equivalent model exhibits specific objectivity if the data fit the model, but the
      congeneric measures model does not. Data from English composition scores on essay
      writing used by Joreskog (1971) are reanalyzed for illustration.

PMID- 15942073
TI  - Modeling local item dependence with the hierarchical generalized linear model.
AB  - Local item dependence (LID) can emerge when the test items are nested within
      common stimuli or item groups. This study proposes a three-level hierarchical
      generalized linear model (HGLM) to model LID when LID is due to such contextual
      effects. The proposed three-level HGLM was examined by analyzing simulated data
      sets and was compared with the Rasch-equivalent two-level HGLM that ignores such
      a nested structure of test items. The results demonstrated that the proposed
      model could capture LID and estimate its magnitude. Also, the two-level HGLM
      resulted in larger mean absolute differences between the true and the estimated
      item difficulties than those from the proposed three-level HGLM. Furthermore, it
      was demonstrated that the proposed three-level HGLM estimated the ability
      distribution variance unaffected by the LID magnitude, while the two-level HGLM
      with no LID consideration increasingly underestimated the ability variance as the
      LID magnitude increased.

PMID- 15942074
TI  - The cross-classified multilevel measurement model: an explanation and
      demonstration.
AB  - The link between the hierarchical generalized linear model (HGLM) and the Rasch
      model's parameterization has already been demonstrated by several researchers.
      Extensions have been described that include higher clustering levels to model
      more appropriately the contextual effects that are frequently encountered in
      educational research. However, pure hierarchies are relatively rare and instead
      cross-classified data structures are more frequently encountered. Cross
      classified random effect modeling (CCREM) is still not commonly used. Use of
      CCREM in combination with the multilevel measurement model (MMM) has been
      recently introduced and is described further in the current study. Specifically,
      the link between the MMM and the CCREM MMM (termed "CCMMM" model) is provided. A
      dataset was simulated to demonstrate interpretation of the CCMMM model's
      parameters and to compare results under a CCMMM versus HGLM analysis. An Appendix
      is provided to demonstrate SAS GLIMMIX code used to estimate HGLM and CCMMM
      models' parameters.

PMID- 15942075
TI  - Test equating in the presence of DIF items.
AB  - This paper proposes a multilevel measurement model that controls for DIF effects
      in test equating. The accuracy and stability of item and ability parameter
      estimates under the proposed multilevel measurement model were examined using
      randomly simulated data. Estimates from the proposed model were compared with
      those resulting from two multiple-group concurrent equating designs, including 1)
      a design that replaced DIF-items with items with no DIF; and 2) a design that
      retained DIF items with no attempt to control for DIF. In most of the
      investigated conditions, the results indicated that the proposed multilevel
      measurement model performed better than the two comparison models.

PMID- 15942076
TI  - A novel ferroportin disease in a Japanese patient.

PMID- 15942077
TI  - Antihypertensive drugs and insulin resistance in obesity.

PMID- 15942078
TI  - Relation between polymorphisms G1704T and G82S of RAGE gene and diabetic
      retinopathy in Japanese type 2 diabetic patients.

PMID- 15942079
TI  - Role of immunoglobulin light chains in Al amyloidosis.

PMID- 15942080
TI  - Cerebral infarction and patent foramen ovale (PFO) in the elderly: is PFO the
      culprit or not?

PMID- 15942081
TI  - Amphotericin B-induced nephrogenic diabetes insipidus.

PMID- 15942082
TI  - Ultrasonographic diagnosis of colitis.

PMID- 15942083
TI  - P53 germline mutations and therapy-related myelodysplastic syndrome.

PMID- 15942084
TI  - Reactive arthritis: recent advances and clinical manifestations.

PMID- 15942085
TI  - Effective prevention of diabetes mellitus: a motto for healthy habits--"none of
      one, less of two, more of three".
AB  - OBJECTIVE: To demonstrate the correlation of six healthy habits with plasma
      glucose. METHODS: Our mnemonic or motto for promoting healthy habits is "none of
      one, less of two, more of three". The 'one' behavior is smoking. The two things
      are intake of food and alcohol. The three things are exercise, rest and enjoyable
      activities. SUBJECTS: A questionnaire recording compliance with this motto was
      completed by 8,113 subjects undergoing medical health check-ups. Subjects under
      medication were excluded. Fasting plasma glucose was measured. RESULTS: Fasting
      plasma glucose decreased significantly in relation to the number of healthy
      habits practiced (5.57 mmol/l for one, 5.51 for two, 5.49 for three, 5.41 for
      four, 5.38 for five, and 5.31 for six) . CONCLUSION: Practicing these six healthy
      habits contributes to the prevention of diabetes mellitus.

PMID- 15942086
TI  - Relation between polymorphisms G1704T and G82S of rage gene and diabetic
      retinopathy in Japanese type 2 diabetic patients.
AB  - OBJECTIVE: To clarify whether polymorphisms G1704T and G82S of the rage gene were
      related to diabetic retinopathy, we performed a case-control study in Japanese
      type 2 diabetic patients. PATIENTS AND METHODS: Two hundred and sixty-eight
      patients with type 2 diabetes were examined for polymorphisms G1704T and G82S of
      the RAGE gene. The genotypes of G1704T and G82S of the RAGE gene were determined
      with a fluorescent allele-specific DNA primer assay system. Diabetic retinopathy
      (DR) was diagnosed in a masked manner by independent ophthalmologists using
      fundus photographs and was classified as non-diabetic retinopathy (NDR), non
      proliferative retinopathy (NPDR), and proliferative retinopathy (PDR). RESULTS:
      The T allele frequency of G1704T and S allele frequency of G82S in patients with
      DR did not significantly differ from those without retinopathy. There were no
      differences among the genotypes of G1704T and G82S of the RAGE gene regarding
      age, duration of diabetes, BMI, HbA(1c), blood pressure, and lipids levels.
      CONCLUSION: These data suggest that polymorphisms G1704T and G82S of the RAGE
      gene are not related to DR in Japanese type 2 diabetic patients.

PMID- 15942087
TI  - Nasal CPAP improves the quality of life and lessens the depressive symptoms in
      patients with obstructive sleep apnea syndrome.
AB  - OBJECTIVE: To assess changes in response to nasal continuous positive airway
      pressure (CPAP) in patients with obstructive sleep apnea syndrome (OSAS)
      concerning excessive daytime sleepiness (EDS), depressive state, and quality of
      life (QOL). PATIENTS AND METHODS: We assessed for EDS using the Epworth
      sleepiness scale (ESS), for mood using The Zung self-depression scale (SDS), and
      for QOL using Short-Form 36 (SF-36) in 132 patients with obstructive sleep apnea
      syndrome (OSAS) and control subjects. Patients had severe OSAS (apnea-hypopnea
      index, 59.4+/-23.8/h) and were more hypersomnolent and depressed, and had poorer
      QOL than 38 age- and gender-matched controls. RESULTS: Before treatment most QOL
      domains in the SF-36 were significantly associated with patients' SDS scores.
      With nasal CPAP, ESS and SDS scores were respectively decreased from 9.7+/-4.5 to
      4.0+/-2.4 (p<0.0001) and from 49.2+/-10.4 to 45.1+/-9.6 (p<0.0005). Total SF-36
      score and scores for seven of eight domains were increased significantly with
      treatment. Thus, nasal CPAP lessens EDS and depression, and improves QOL, in
      patients with severe OSAS. Further, magnitudes of changes in total SF-36 scores
      and in five of eight domains correlated significantly with magnitude of change in
      SDS score upon nasal CPAP treatment. No relationship was evident between
      treatment-associated score changes in SF-36 domains and ESS score change.
      CONCLUSION: Although patients with severe OSAS have poorer QOL than control
      subjects, nasal CPAP appears to improve QOL by alleviating depression.

PMID- 15942088
TI  - Serum levels of free light chain before and after chemotherapy in primary
      systemic AL amyloidosis.
AB  - OBJECTIVE: Immunoglobulin-related free light chains (FLCs) in serum have recently
      become quantitatively detectable using the nephelometric assay in plasma cell
      disorders, including multiple myeloma and AL amyloidosis. To investigate whether
      FLCs are useful as a diagnostic and therapeutic marker in Japanese patients with
      primary systemic AL amyloidosis, we determined these values in serum before and
      after chemotherapy. PATIENTS AND METHODS: The serum FLC analysis was carried out
      in 25 patients with primary systemic AL amyloidosis (mean age, 60.1+/-8.4 years).
      All of the patients were shown to have either ALkappa- or ALlambda-immunoreactive
      amyloid deposits on biopsied tissues. Thirteen patients were treated with VAD
      (vincristine, doxorubicin and dexamethasone) alone (n=6) or VAD and subsequent
      high-dose melphalan followed by autologous stem cell support (n=7), and serum
      FLCs were serially determined before and after the chemotherapy. RESULTS: Before
      chemotherapy the amyloidogenic FLC was elevated in serum with or without abnormal
      e/e ratios in 24 patients, including 5 with undetectable M-protein in both serum
      and urine on immunofixation. After chemotherapy the amyloidogenic FLC in serum
      was significantly decreased irrespective of high-dose melphalan (p<0.05), and all
      the patients with normalized kappa/lambda ratios showed a good prognosis.
      CONCLUSIONS: With respect to sensitivity and quantification serum FLCs will be a
      key marker for diagnosis and therapeutic effects in primary systemic AL
      amyloidosis. The prognosis of patients with this disease may be improved if the
      kappa/lambda ratio in serum can be normalized by intensive chemotherapy.

PMID- 15942089
TI  - Is stroke a paradoxical embolism in patients with patent foramen ovale?
AB  - OBJECTIVE: Purpose was to assess the stroke mechanism in patients with patent
      foramen ovale (PFO). METHODS: We reviewed the medical records of 111 stroke
      patients with PFO and sinus rhythm (PFO-S group), 25 with PFO and atrial
      fibrillation (AF) (PFO-AF group) and 67 with AF but not PFO (AF group), who had
      received contrast transesophageal echocardiography. The clinical and
      neuroradiological findings were then compared among the three groups. Deep vein
      thrombosis was investigated in 93 patients with PFO. We determined the number of
      patients with definite paradoxical embolism who met three criteria: deep vein
      thrombosis, neuroradiological features indicating embolic stroke, and the absence
      of other sources of emboli. We also evaluated those with probable paradoxical
      embolism who met two of the three criteria. RESULTS: The PFO-S group more
      frequently exhibited hypercholesterolemia (p<0.0001) and lesions limited to the
      posterior circulation (p<0.0004), and less frequently exhibited large or cortical
      lesions in the anterior circulation (p=0.0008, p<0.0001, respectively), than the
      PFO-AF and AF groups. In the PFO-S and PFO-AF groups, other sources of emboli
      such as a cardiac source of emboli, cerebral artery stenosis > or =50%, or
      complicated atheroma in the aortic arch were identified in 72 cases (52.9%). In
      the 93 patients with examination for deep vein thrombosis, the definite and
      probable criteria of paradoxical embolism were fulfilled only in three (3.2%) and
      33 cases (35.5%), respectively. CONCLUSION: In stroke patients with PFO, not only
      paradoxical brain embolism through the PFO but also other causes of stroke may
      contribute to the development of stroke.

PMID- 15942090
TI  - Small hepatocellular carcinoma associated with Wilson's disease.
AB  - We report a 66-year-old male patient with hepatocellular carcinoma (HCC)
      associated with Wilson's disease. The patient presented with unresolving abnormal
      liver function test, decreased serum ceruloplasmin levels and increased 24-hour
      urine copper excretion. Liver biopsy specimen revealed the presence of increased
      levels of copper and features suggestive of Wilson's disease. Abdominal imaging
      showed the existence of a small HCC. Three years after chemoembolization and
      microwave coagulation therapy for HCC, he died of hepatic failure, which
      apparently resulted from chemoembolization. Patients with Wilson's disease should
      be screened for HCC. We should elude therapies such as chemoembolization in these
      patients.

PMID- 15942091
TI  - Unusual metastasis of hepatocellular carcinoma to the esophagus.
AB  - This report describes a case of metastatic hepatocellular carcinoma (HCC)
      presenting as a polypoid mass in the lower esophagus. The patient was a 63-year
      old man with HCC. An endoscopic examination revealed a pedunculated polypoid
      mass, about 3 cm in diameter, at the lower part of the esophagus. The biopsy
      specimen obtained from the tumor revealed that the mass consisted of a
      pseudoglandular arrangement of tumor cells, and the tumor was diagnosed as
      metastatic HCC. There were no symptoms due to esophageal tumor. He died of
      progressive hepatic failure. Cases of premortem-diagnosed esophageal metastasis
      from HCC are extremely rare.

PMID- 15942092
TI  - Hypermagnesemia induced by massive cathartic ingestion in an elderly woman
      without pre-existing renal dysfunction.
AB  - A 76-year-old woman was referred to our hospital for unresponsiveness and
      hypotension. She had developed constipation that had led to ileus and had
      received 34 g of magnesium citrate (Magcolol P) orally the day before. She was
      lethargic, her blood pressure was less than 50 mmHg, and electrocardiogram (ECG)
      revealed sinus arrest with junctional escape rhythm. Her serum concentration of
      magnesium (Mg) was markedly elevated (16.6 mg/dl =13.7 mEq/l). Emergency
      colonoscopy revealed ischemic colitis. As her condition ameliorated, her renal
      function returned to normal. Hence, the present case suggests that severe
      hypermagnesemia can occur in the absence of pre-existing renal dysfunction in
      elderly patients with gastrointestinal diseases.

PMID- 15942093
TI  - Platypnea-orthodeoxia syndrome combined with multiple congenital heart anomalies.
AB  - A 71-year-old woman was admitted for paralysis on the left side of her body. She
      developed dyspnea and hypoxemia after admission. Although pulmonary embolism was
      suspected, hypoxemia and dyspnea occurred repeatedly in spite of anticoagulation
      therapy. Transesophageal echocardiography revealed a patent foramen ovale (PFO),
      an atrial septal aneurysm (ASA), and a right-to-left shunt that appeared in an
      upright position. She was diagnosed with platypnea-orthodeoxia syndrome.
      Moreover, cardiac catheterization showed congenital anomalies, such as unroofed
      coronary sinus, partial anomalous pulmonary venous return and persistent left
      superior vena cava. Simple surgical closure of the ASA and PFO improved all of
      her symptoms.

PMID- 15942094
TI  - Amphotericin B-induced nephrogenic diabetes insipidus in a case of
      cryptococcemia.
AB  - A 66-year-old woman with malignant lymphoma became neutropenic during
      chemotherapy and developed cryptococcemia. After amphotericin B had been
      commenced, she developed significant hypokalemia and polyuria, though her renal
      function remained stable. The laboratory findings showed no evidence of renal
      tubular acidosis. With vigorous water and potassium replacement, amphotericin B
      had been continued until the cumulative dose reached 2.5 g. After the cessation
      of amphotericin B, the hypokalemia and polyuria resolved promptly. Based on
      theses findings, she was diagnosed as nephrogenic diabetes insipidus with
      hypokalemia and without renal tubular acidosis due to amphotericin B. This
      complication is usually reversible, and vigorous water and potassium replacement
      may allow completion of treatment by amphotericin B, though careful monitoring of
      body water balance and renal function is of importance.

PMID- 15942095
TI  - Multifocal micronodular pneumocyte hyperplasia in a man with tuberous sclerosis.
AB  - We report a peculiar case of multifocal micronodular pneumocyte hyperplasia
      (MMPH) occurring in a 43-year-old man with tuberous sclerosis. Computed
      tomography of the chest demonstrated multiple micronodules, measuring up to 5 mm
      in size, present bilaterally in the lung fields, with no cystic change.
      Histologically, a proliferation of type II pneumocytes without the typical
      nulclear atypia lined the thickened alveolar septa in an adenomatoid pattern.
      Proliferation of immature smooth muscle cells suggestive of LAM was not observed.
      The characteristic findings of the positive immunohistochemical stains for
      cytokeratin and surfactant apoprotein A and B, and negative stains for HMB-45,
      alpha-1 smooth muscle actin, desmin, p53 and carcinoembryonic antigen confirmed
      the presence of alveolar lining cells in each MMPH lesion. Since the MMPH was
      observed in a male and did not appear to possess malignant potential, the MMPH
      appears to be a hamartomatous proliferation occurring in a male with tuberous
      sclerosis that is separate from lymphangiomyomatosis (LAM) which is related to
      estrogen and progesterone receptors.

PMID- 15942096
TI  - Neutropenic enterocolitis in lung cancer: a report of two cases and a review of
      the literature.
AB  - The first patient, a 68-year-old woman, presented neutropenic fever and
      hemorrhagic diarrhea on the sixth day of a combination chemotherapy of
      carboplatin and paclitaxel. The second patient, a 30-year-old man, presented
      neutropenia and diarrhea on the tenth day of the second cycle of a combination
      chemotherapy of cisplatin and vinorelbine. In both patients, abdominal computed
      tomography scan showed thickening of the colon wall and pericolic edema, and the
      ultrasonography revealed echogenic thickening of the colon walls. These findings
      confirmed the diagnosis of neutropenic enterocolitis. After the treatments, we
      changed the anticancer drug regimen; and successfully achieved partial responses.

PMID- 15942097
TI  - High-dose cyclophosphamide as an effective therapy for a patient with refractory
      multiple myeloma relapsing after autologous stem cell transplantation.
AB  - Alkylating agents are often used to treat patients with multiple myeloma (MM).
      However, it is not common for high-dose cyclophosphamide (CPM) therapy to be used
      as a treatment for MM. Herein, we report a case of refractory MM associated with
      hypercalcemia. We decided to give her high-dose CPM. After this treatment, the
      serum calcium level decreased and the tumor mass in the iliac bone was reduced.
      This therapy is potentially useful for patients with refractory MM.

PMID- 15942098
TI  - Successful reduced-intensity stem cell transplantation (RIST) for a patient with
      malignant lymphoma and an ileostomy.
AB  - A 56-year-old man was admitted for treatment of non-Hodgkin's lymphoma (NHL). He
      had undergone a partial small bowel and colon resection and had ileostomy due to
      bowel perforation induced by chemotherapy. After the operation, his disease
      status was in partial remission (PR), and reduced-intensity allogeneic stem cell
      transplantation (RIST) was therefore performed for further improvement of disease
      status. The conditioning regimen consisted of fludarabine and busulfan. Graft
      versus-host disease (GVHD) prophylaxis was performed using cyclosporin and short
      term methotrexate. The occurrence of serious infection during the period of
      neutropenia was prevented by the administration of amphotericin B, fluconazole
      and acyclovir. This case report provides important information on the appropriate
      strategy for treating patients who have ileostomy.

PMID- 15942099
TI  - Scrotal Ulcers Arising during Treatment with All-trans Retinoic Acid for Acute
      Promyelocytic Leukemia.
AB  - All-trans retinoic acid (ATRA) is effective in approximately 90% of the cases of
      acute promyelocytic leukemia (APL) with a low incidence of adverse effects. We
      report a patient with APL who developed skin ulcers of the scrotum concomitant
      with high fever during treatment that included ATRA. Severe fever was promptly
      alleviated with discontinuation of ATRA, while the ulcers improved gradually over
      3 months. As the clinical features are similar to those of Sweet's syndrome, we
      should be aware of the possibility that this rare adverse effect may occur in the
      treatment with ATRA.

PMID- 15942100
TI  - High-dose melphalan followed by autologous stem cell support in primary systemic
      AL amyloidosis with multiple organ involvement.
AB  - A patient with primary systemic AL amyloidosis achieved partial hematological
      response after 2 courses of VAD (vincristine, doxorubicin and dexamethasone) and
      subsequent high-dose melphalan followed by autologous peripheral blood stem cell
      transplantation despite involvement of multiple organs, including the heart. In
      this patient natriuretic peptides and free light chains in serum were useful as
      markers of cardiac involvement and therapeutic effects, respectively. When
      amyloidosis-related dysfunction is seen in multiple organs, this intensive
      chemotherapy might be a possible therapeutic option, although several
      modifications in the regimen and careful management are necessary.

PMID- 15942101
TI  - A patient with TP53 germline mutation developed Bowen's disease and
      myelodysplastic syndrome with myelofibrosis after chemotherapy against ovarian
      cancer.
AB  - Here we report a case of myelodysplastic syndrome (MDS) with myelofibrosis
      associated with Bowen's disease. A female patient had undergone an operation and
      chemotherapy for ovarian cancer when she was 65 years old, and she developed MDS
      at the age of 70 years old. PCR-single strand conformation polymorphism (SSCP)
      analysis of peripheral blood mononuclear cells, a Bowen's disease lesion, and
      normal skin showed an abnormal peak in TP53 exon5. Direct sequencing revealed
      that they all had missense mutation in codon 175 (G to A) of arginine switched to
      histidine, suggesting a germline mutation of TP53. It was speculated that p53
      function was lost by TP53 germline mutation with the loss of a wild type allele
      induced by the chemotherapy against ovarian cancer, leading to the development of
      MDS. No therapeutic effects of low dose melphalan or cyclosporine A on MDS were
      observed, however one month of 30 mg/day prednisolone administration induced a
      hematological response.

PMID- 15942102
TI  - Churg-Strauss syndrome associated with hypersensitivity to acetaminophen.
AB  - Acetaminophen is a widely used antipyretic drug. We describe a 64-year-old
      Japanese woman who developed typical Churg-Strauss syndrome after frequent use of
      acetaminophen. Following the ingestion of acetaminophen, she exhibited various
      allergic reactions such as asthmatic attacks, pyrexia and petechiae on legs. In
      the lymphocyte transformation test, a positive reaction to acetaminophen was
      detected. A muscle biopsy revealed massive extravascular eosinophil infiltration
      and a necrotizing vasculitis. Hypersensitivity to acetaminophen may be implicated
      in the development of Churg-Strauss syndrome in this case.

PMID- 15942103
TI  - Fulminant massive gas gangrene caused by Clostridium perfringens.
AB  - Clostridium perfringens (C.P) gas gangrene is one of the most fulminant
      infectious diseases. We encountered fulminant massive gas gangrene in a 56- year
      old man with alcoholic liver cirrhosis. The patient died 14 hours after diagnosis
      of gas gangrene (54 hours after admission). Dramatic changes in abdominal CT
      imaging revealed development of a massive volume of gas in the intra-portal vein,
      retroperitoneum and abdominal subcutaneous tissue within 24 hours. We also proved
      C.P infection by immunohistological staining, leading to a diagnosis of C.P gas
      gangrene.

PMID- 15942104
TI  - Focal nodular hyperplasia of the liver with angioma-like features in the center.

PMID- 15942105
TI  - Ischemic stroke in a young adult due to dissection of a branch of the middle
      cerebral artery.

PMID- 15942106
TI  - Persistent primitive hypoglossal artery with atrial septal defect.

PMID- 15942107
TI  - Reactive arthritis due to asymptomatic infection of Chlamydia trachomatis.

PMID- 15942108
TI  - Situs inversus: a laparoscopic observation.

PMID- 15942109
TI  - Sixteen-slice computed tomography, transthoracic real-time 3-dimensional
      echocardiography and magnetic resonance imaging assessment of a long-term
      survivor of rupture of sinus of valsalva aneurysm.

PMID- 15942110
TI  - Biphasic pulmonary blastoma presenting as endobronchial polyp with a long stalk.

PMID- 15942111
TI  - Viral pneumonia: coinfection of cytomegalovirus and herpes simplex virus.

PMID- 15942112
TI  - Crossed pontine infarction caused by vertebro-basilar artery dissection.

PMID- 15942113
TI  - Paraneoplastic neurologic syndrome associated with small breast cancer:
      diagnostic value of FDG-PET for detection of underlying malignancy.

PMID- 15942114
TI  - MRI of adult-onset type II citrullinemia.

PMID- 15942115
TI  - Measurement of small dense low-density lipoprotein particles.
AB  - Low density lipoprotein (LDL) particles are heterogeneous with respect to their
      size, density and lipid composition. Among LDL particles, the smaller and denser
      LDL particles [small dense (sd) LDL] are more atherogenic and the sd LDL
      phenotype is strongly associated with development of coronary heart disease. Here
      we will review various methods for measurement of sd LDL. Although
      ultracentrifugation, nuclear magnetic resonance (NMR) spectroscopy and gradient
      gel electrophoresis (GGE) are usually employed for the measurement of sd LDL,
      such methods are either too laborious or expensive for general clinical use. We
      recently established a simple precipitation method for the quantification of sd
      LDL. This method is applicable to routine clinical use and allows the rapid
      measurement of a large number of samples.

PMID- 15942116
TI  - Remnant lipoproteins and atherogenesis.
AB  - Recent clinical studies have revealed that increased serum triglyceride (TG)
      levels are closely related to atherosclerosis, independently of serum levels of
      high-density lipoproteins (HDL) and low-density lipoproteins (LDL). Among
      triglyceride-rich lipoproteins (TRLs), remnant lipoproteins (RLPs) are considered
      to be atherogenic and an independent coronary risk factor. We previously reported
      that monocytes cultured in the presence of RLPs increased their adhesion to
      vascular endothelial cells. The underlying mechanism involved activation of RhoA,
      a member of small GTP binding proteins, resulting in activation of focal adhesion
      kinase (FAK) and s1-integrin. It is also known that RLPs enter vessel walls. In
      another study, we reported that RLPs induced smooth muscle cell (SMC)
      proliferation, independently of oxidative stress. Recently, we identified the
      molecular mechanisms, in which RLPs from hypertriglyceridemic patients stimulated
      SMC proliferation via epidermal growth factor (EGF) receptor transactivation and
      heparin-binding EGF-like growth factor (HB-EGF) shedding. More recently, we
      reported that apoB48 receptor was involved in RLP-induced foam cell formation in
      macrophages. The current review focused on the molecular mechanisms for the
      atherogenicity of RLPs.

PMID- 15942117
TI  - Effects of atorvastatin on glucose metabolism and insulin resistance in KK/Ay
      mice.
AB  - Insulin resistance plays an important role not only in the development and
      progression of diabetes mellitus but also in the establishment of metabolic
      syndrome. Improvement of insulin resistance is thus of great importance both in
      improving glucose metabolism and preventing atherosclerosis. Although HMG-CoA
      reductase inhibitors appear to favorably affect glucose metabolism, as indicated
      by the results of a subanalysis in the West of Scotland Coronary Prevention Study
      (WOSCOPS), their effects on glucose metabolism and insulin resistance have not
      been thoroughly investigated in animal models. In this study, the effects of
      atorvastatin on the glucose metabolism and insulin resistance of KK/Ay mice, an
      animal model of type II diabetes, were investigated. Atorvastatin significantly
      decreased the non-HDL-cholesterol level in the oral glucose tolerance test,
      inhibited increase in the 30-min glucose level, decreased plasma insulin levels
      before and 30 and 60 minutes after glucose loading, and decreased the insulin
      resistance index, compared with corresponding values in controls, indicating that
      atorvastatin appeared to improve glucose metabolism by improving insulin
      resistance. Northern blot analysis revealed decreases in levels of mRNA of sterol
      regulatory element binding protein-1 (SREBP-1) and glucose-6-phosphatase
      (G6Pase), and it may play a role in the improvement of glucose metabolism and
      insulin resistance.

PMID- 15942118
TI  - Association between abdominal wall fat index on ultrasonography and carotid
      atherosclerosis in non-obese men.
AB  - We tried to investigate whether accumulation of visceral fat, assessed by a
      simple but widely used ultrasonographic method, was associated with common
      carotid atherosclerosis in non-obese men ranging from 16 to 79 years old. The
      subjects were consecutive 297 male in-patients whose body mass index ranged from
      18.5 kg/m(2) to 25 kg/m(2). An ultrasonographic evaluation using a 7.5 MHz linear
      type B-mode probe was performed by a specialist to determine the intima-media
      thickness (IMT) of the common carotid artery and the maximal thickness of
      peritoneal fat (Pmax) at the anterior surface of the liver and the minimal
      thickness of subcutaneous fat (Smin) of the abdomen. The Pmax/Smin ratio, which
      was termed the abdominal wall fat index (AFI), was then calculated. The mean age
      +/- standard deviation in this series was 65 +/- 13 (range, 15-79) years.
      Multiple regression analysis using IMT as an objective variable, adjusted by
      various risk factors as explanatory variables, showed that AFI [beta, 0.0538; 95%
      confidence interval (CI), 0.0116-0.0960] was a significant independent
      contributing factor along with known risk factors such as age, smoking status,
      systolic blood pressure, HDL-cholesterol and LDL-cholesterol. We found that AFI
      was useful in evaluating disorders of metabolism and atherosclerosis in non-obese
      men.

PMID- 15942119
TI  - Apoptosis induced by 7-ketocholesterol is enhanced in smooth muscle cells derived
      from OLETF rats.
AB  - To clarify whether an increased proliferative potential of vascular smooth muscle
      cells (SMC) under diabetic conditions augments the susceptibility of the cells to
      7-ketocholesterol-induced apoptosis, we investigated the difference in
      sensitivity to 7-ketocholesterol between SMC obtained from diabetic Otsuka Long
      Evans Tokushima fatty (OLETF) rats and the control Long-Evans Tokushima Otsuka
      (LETO) rats. The outgrowth rate from aortic wall explants and cell proliferation
      were higher in SMC derived from OLETF rats (OLETF-derived SMC) compared to those
      from LETO rats (LETO-derived SMC). When 7-ketocholesterol was added to SMC, the
      amount of fragmented DNA increased significantly in OLETF-derived compared to
      LETO-derived SMC. The amount of fragmented DNA induced by 7-ketocholesterol
      decreased significantly in both OLETF- and LETO-derived SMC when they were
      incubated without fetal bovine serum. By adding PDGF-BB to LETO-derived SMC, the
      amount of fragmented DNA induced by 7-ketocholesterol increased significantly.
      These results suggest that apoptosis of SMC induced by 7-ketocholesterol may be
      accelerated when SMC acquire a high proliferative potential by prolonged exposure
      to diabetic condition.

PMID- 15942120
TI  - Serum lipid survey and its recent trend in the general Japanese population in
      2000.
AB  - To determine the recent serum lipid levels and other serum variables in the
      general Japanese population and trends in their changes over the past 40 years, a
      nationwide survey of serum lipid levels was conducted in 36 institutes from
      various districts around Japan in 2000. The total number of subjects was 12,839,
      aged 4 through 99 years. The mean total cholesterol level was 201 mg/dl; 202
      mg/dl in men and 200 mg/dl in women. The mean HDL-cholesterol level was 59 mg/dl;
      55 mg/dl in men and 65 mg/dl in women. The mean LDL-cholesterol level was 118
      mg/dl; 121 mg/dl in men and 115 mg/dl in women. The mean triglyceride level was
      118 mg/dl; 136 mg/dl in men and 92 mg/dl in women. The total cholesterol level
      slightly increased by 5 mg/dl in 10 years. Although the triglyceride level in
      women did not change, the triglyceride level in men increased over 10 years,
      especially in the 30s through 70s age bracket, indicating a possible increase in
      metabolic syndromes in the future. The present results will become the standard
      serum lipid level data for the Japanese people, and succeeding 10-year surveys
      will clarify the trends of lipid levels in this country.

PMID- 15942121
TI  - The relationship between non-HDL cholesterol and other lipid parameters in
      Japanese subjects.
AB  - Plasma non-HDL cholesterol (HDL-C) concentration that is simply estimated from
      plasma total cholesterol and HDL-C concentrations, without the influence of
      plasma triglyceride concentration, has been included as a therapeutic target for
      hypertriglyceridemic patients in the most recent National Cholesterol Education
      Program (NCEP) recommendations. In the present study, we estimated plasma non-HDL
      C concentration in Japanese subjects to clarify the correlation of plasma non-HDL
      C to other plasma lipid concentrations, and to evaluate the NCEP recommendation.
      Plasma non-HDL-C concentration has a positive correlation with low-density
      lipoprotein cholesterol (LDL-C) and triglyceride concentrations. From our
      analysis, 140 mg/dl of plasma LDL-C concentration, which is the level for the
      diagnosis of hyper-LDL cholesterolemia, corresponds to 169 mg/dl of non HDL-C
      concentration. The relationship between plasma non-HDL-C and LDL-C concentrations
      in Japanese subjects is quite similar to that described in the NCEP guideline.
      Thus, we suggest that non-HDL-C is a useful risk marker in Japan, as recommended
      by the NCEP.

PMID- 15942122
TI  - Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in
      hypercholesterolemic patients.
AB  - Reduction of serum cholesterol levels with statin therapy decreases the risk of
      coronary heart disease. Inhibition of HMG-CoA reductase by statin results in
      decreased synthesis of cholesterol and other products downstream of mevalonate,
      which may produce adverse effects in statin therapy. We studied the reductions of
      serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients
      treated with atorvastatin. Fourteen patients were treated with 10 mg/day of
      atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were
      measured before and after 8 weeks of treatment. Serum total cholesterol and LDL
      cholesterol levels decreased significantly. All patients showed definite
      reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of
      serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/-
      0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/-
      0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and
      those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165).
      As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in
      all patients, it is imperative that physicians are forewarned about the risks
      associated with ubiquinol-10 depletion.

PMID- 15942123
TI  - Baicalein prevents 6-hydroxydopamine-induced dopaminergic dysfunction and lipid
      peroxidation in mice.
AB  - The effects of baicalein on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity were
      evaluated. Intracerebroventricularly (i.c.v.) injection of 6-OHDA was done to
      young mice. Baicalein was administered intraperitoneally 30 min before and 90 min
      after i.c.v. injection. Animals received further injection of bacalein daily for
      3 consecutive days. Rotarod performance was assessed, tyrosine hydroxylase (TH)
      Western blotting was performed, and dopamine (DA) levels and peroxidation were
      determined. High dose of baicalein effectively improved rotarod performance and
      prevented the reduction of striatal DA levels and TH contents in the striatum and
      subtantia nigra (SN). In addition, lipid peroxidation level was decreased by
      baicalein at 3 and 7 days after 6-OHDA injection. These results showed that
      baicalein effectively prevents the 6-OHDA-induced dopaminergic dysfunction
      through an antioxidative action.

PMID- 15942124
TI  - Mechanisms involved in the contraction of intrahepatic portal vein branches by
      clomipramine and oxethazaine in isolated perfused rat livers.
AB  - Clomipramine (CLM) and oxethazaine (OXZ) were previously reported to increase
      portal pressure by contracting portal vein branches (PVBs) in isolated perfused
      rat liver. In the present study, to characterize the contractile mechanisms, the
      effects of Y27632, HA1077, staurosporine, papaverine, SKF96365, and sulindac
      sulfide on the portal pressure increase induced by CLM and OXZ were examined
      comparatively with those induced by endothelin-1. The results suggest that 1)
      intrahepatic PVBs employ a Rho-kinase-dependent pathway for sustained
      contraction, 2) CLM contracts PVBs by activating a Rho-kinase pathway and Ca(2+)
      channels, and 3) OXZ acts primarily by promoting Ca(2+) entry through its
      ionophore-like action.

PMID- 15942125
TI  - Loperamide inhibits tachykinin NK3-receptor-triggered serotonin release without
      affecting NK2-receptor-triggered serotonin release from guinea pig colonic
      mucosa.
AB  - The effect of loperamide on tachykinin NK(2)- and NK(3)-receptor-mediated 5-HT
      outflow from guinea pig colonic mucosa was investigated in vitro. The selective
      tachykinin NK(2)-receptor agonist [beta-Ala(8)]-neurokinin A(4-10) (betaAla-NKA)
      or the selective NK(3)-receptor agonist senktide elicited an increase in 5-HT
      outflow from whole colonic strips, but not from mucosa-free muscle layer
      preparations. The enhancing effect of betaAla-NKA and senktide was prevented by
      the selective NK(2)-receptor antagonist GR94800 or the selective NK(3)-receptor
      antagonist SB222200. Loperamide concentration-dependently suppressed the senktide
      evoked 5-HT outflow, but failed to affect the betaAla-NKA-evoked 5-HT outflow.
      The kappa-opioid receptor antagonist nor-binaltorphimine or the delta-opioid
      receptor antagonist naltrindole displaced the concentration-response curve for
      the suppressant action of loperamide to the right without significant depression
      of the maximum. However, the mu-opioid receptor antagonist CTOP did not affect
      the suppressant effect of loperamide. We concluded that the NK(3) receptor
      triggered 5-HT release from colonic mucosa is suppressed by loperamide-sensitive
      mechanisms, whereas the NK(2)-receptor-triggered 5-HT release is loperamide
      insensitive. Our data also suggest that the suppressant effect of loperamide is
      probably mediated by the activation of kappa- and delta-opioid receptors located
      on intrinsic neurons.

PMID- 15942126
TI  - Caveolae-independent activation of protein kinase A in rat neonatal myocytes.
AB  - Cardiomyocytes express both beta(1)- and beta(2)-adrenergic receptors, and these
      receptors play a differential role in chronotropic and inotropic effects of the
      heart. Caveolae are known as an important regulator of G-protein-coupled receptor
      signaling. In the present report, we examined whether caveolae have a role in
      beta-adrenergic receptor-stimulated cAMP production and protein kinase A
      activation in neonatal myocytes. Isoproterenol-stimulated cAMP production was
      mediated by beta(1)- and beta(2)-subtypes, which depends on the receptor number
      of each subtype. However, protein kinase A activation was exclusively mediated by
      the beta(1)-subtype. Disruption of caveolae by methyl-beta-cyclodextrin treatment
      did not affect the relative contribution of subtypes to isoproterenol-stimulated
      cAMP production. beta(1)-Subtype-mediated protein kinase A activation was also
      not affected by the disruption of caveolae. These results suggest that beta(1)
      adrenergic receptor-mediated protein kinase A activation is compartmentalized and
      independent of caveolae.

PMID- 15942127
TI  - Nitric oxide inhibits the bradykinin B2 receptor-mediated adrenomedullary
      catecholamine release but has no effect on adrenal blood flow response in vivo.
AB  - The role of nitric oxide (NO) in bradykinin (BK)-induced adrenal catecholamine
      secretion still remains obscure. The present study was to investigate whether an
      inhibition of NO synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME)
      would modulate BK-induced adrenal catecholamine secretion (ACS) and adrenal
      vasodilating response (AVR) in anesthetized dogs. Plasma catecholamine
      concentrations were determined with an HPLC coupled with an electrochemical
      detector. All drugs were locally administered to the left adrenal gland via intra
      arterial infusion. BK dose-dependently increased both ACS and AVR. Hoe-140, a
      selective B(2) antagonist, significantly blocked the BK-induced increases in both
      ACS and AVR. In the presence of L-NAME, the BK-induced ACS was significantly
      enhanced, while the simultaneous AVR remained unaffected. These results suggest
      that the both BK-induced ACS and AVR are primarily mediated by B(2) receptors in
      the canine adrenal gland. Our results also suggest that the enhanced ACS in
      response to BK in the presence of L-NAME may have resulted from a specific
      inhibition of NO formation in the adrenal gland. It is concluded that the BK
      induced NO may play an inhibitory role in the B(2)-receptor-mediated mechanisms
      regulating ACS, while it may not be implicated in the B(2)-receptor-mediated AVR
      under in vivo conditions.

PMID- 15942128
TI  - Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa
      opioid receptors.
AB  - The opioid analgesic, butorphanol (17-cyclobutylmethyl-3,14-dihydroxymorphinan)
      tartrate is a prototypical agonist-antagonist opioid analgesic agent whose
      potential for abuse has been the cause of litigation in the United States. With a
      published affinity for opioid receptors in vitro of 1:4:25 (mu:delta:kappa), the
      relative contribution of actions at each of these receptors to the in vivo
      actions of the drug are an issue of active investigation. A body of evidence has
      been developed which indicates that a substantial selective action of butorphanol
      on the kappa-opioid receptor mediates the development of tolerance to butorphanol
      and cross-tolerance to other opioid agonists; to the production of dependence
      upon butorphanol, particularly in the rodent; and to compensatory alterations in
      brain opioid receptor-effector systems. This perspective will identify the
      current state of understanding of the effects produced by butorphanol on brain
      opioid receptors, particularly on the kappa-opioid receptor subtype, and on the
      expression of phosphotyrosyl proteins following chronic treatment with
      butorphanol.

PMID- 15942129
TI  - Renal effects of medetomidine in isoflurane-anesthetized dogs with special
      reference to its diuretic action.
AB  - Renal effects of the selective alpha(2)-adrenoceptor agonist, medetomidine, were
      investigated in anesthetized dogs. Animals were administered medetomidine 20 and
      40 microg/kg intravenously (IV) and 80 mug/kg intramuscularly (IM) or 1 ml of
      saline IV. Urine and blood samples were collected before and at 30, 60, 90 and
      120 min following medetomidine injection. Mean arterial blood pressure (MABP),
      renal blood flow (RBF), glomerular filtration rate (GFR), urine volume (U(v)),
      urine osmolality (U(osm)), free water clearance (C(H2O)), fractional clearance of
      sodium (F(Na)), plasma osmolality (P(osm)), plasma glucose levels and plasma
      antidiuretic hormone (ADH) concentrations were measured. The results showed that
      IV administration of medetomidine initially increased MABP 5-15 min followed by
      long-lasting decrease. The initial hypertension was not observed after IM
      administration, which was accompanied by a more profound hypotensive effects.
      RBF, GFR, U(v), C(H2O) increased after IV injection and decreased after IM.
      Medetomidine increased FNa and Posm and decreased U(osm). Plasma glucose levels
      initially increased and subsequently decreased. Plasma ADH concentration was
      decreased by IV injection but increased by IM administration. Our data imply
      that: 1) IV administration of medetomidine at dose rates of 20 and 40 microg/kg
      results in profound diuresis up to 2 hr; 2) Suppression of ADH release from the
      CNS is one of the mechanisms of medetomidine-induced diuresis although it may not
      be the principal one.

PMID- 15942130
TI  - Epidemiological survey of Babesia gibsoni infection in dogs in eastern Japan.
AB  - To determine the distribution of Babesia gibsoni infection in dogs in the eastern
      part of Japan, an epidemiological survey of dogs suspected of having B. gibsoni
      infection was attempted using the polymerase chain reaction (PCR) and enzyme
      linked immunosorbent assay (ELISA). Thirty-five of 115 such dogs (30.4%) were
      positive by PCR and/or ELISA. The 35 positive dogs consisted of 28 Tosa dogs, 4
      American Pit Bull Terriers, and 3 mongrel dogs in Aomori, Fukushima, Ibaraki,
      Gunma, Chiba, Tokyo, Kanagawa, and Nagano Prefectures. The positive dogs had a
      significantly lower rate of tick exposure and a higher rate of bites by other
      dogs. Twenty-two of 35 B. gibsoni-positive dogs were infected with hemoplasma,
      and the rate of infection was significantly higher than that of B. gibsoni
      negative dogs.

PMID- 15942131
TI  - Microanatomy of the terminal air spaces of Baird's beaked whale (Berardius
      bairdii) lungs.
AB  - The terminal airways and microvasculature of five adult Baird's beaked whales
      (Berardius bairdii) lungs have been examined by means of light and scanning
      electron microscopy of corrosion casts. The respiratory system of the Baird's
      beaked whale has various anatomical features which allow them to attain great
      depths and remain submerged for long periods. The whale lung has components
      including hyaline cartilage and smooth muscle throughout, reaching as far as the
      peripheral bronchi, sphincters surrounding the terminal bronchioles, the thick
      alveolar septa with a connective tissue core and a bi-layer capillary bed, and a
      distinctive venous plexus of the pulmonary veins. The well-developed venous
      plexuses of the pulmonary vein are found in the interlobular connective tissue,
      and around the airways and pulmonary arteries with close apposition. The hyaline
      cartilage throughout the airways may increase the effective dead air space that
      accommodates most of the air forced from the collapsed alveoli during a dive. The
      sphincter might serve as a cock for regulating buoyancy and for trapping air in
      the alveoli to prevent their complete collapse and a sucking in of alveolar
      tissue as the dive becomes deeper. The venous plexuses might be for pooling the
      large volume of blood in the lung to conserve oxygen for deep and prolonged
      diving.

PMID- 15942132
TI  - Histopathological characterization of the skeletal myopathy in rasH2 mice
      carrying human prototype c-Ha-ras gene.
AB  - A skeletal myopathy is found in approximately 100% of rasH2 mice. To confirm
      detailed features of the rasH2 skeletal myopathy, the biceps femoris, diaphragm,
      triceps brachii, gastrocnemial (types I and II fiber-mixed muscles) and soleus
      muscle (type I fiber-dominant muscle) obtained from male rasH2 and non-transgenic
      littermates aged 10-13 and 34 weeks were examined. Variations in the muscle fiber
      size, early-scattered degeneration/necrosis and regeneration of muscle fibers
      were detected in 10-13-week-old rasH2 mice. The severity of the above muscular
      lesions was more prominent in older rasH2 mice. These lesions were noted in the
      type II myofiber dominant muscles (biceps femoris, triceps brachii and
      gastrocnemial). NADH-TR stain clearly demonstrated a disorganized
      intermyofibrillar network and necrotic change in muscle fibers. No specific
      morphological changes, like rod structure or tubular aggregation seen in some
      types of myopathy, were noted in Gomori trichrome and NADH-TR stains in the rasH2
      mouse like in many types of muscular dystrophy. Electronmicroscopically,
      occasional muscle fiber degeneration/regeneration, invaded phagocytic cells,
      indistinct Z-band suggesting excessive contraction and dilatation of the
      sarcoplasmic reticulum were observed. In summary, the skeletal myopathy occurring
      in rasH2 mice is consistent with muscular dystrophy characterized morphologically
      by progressive degeneration and regeneration of myofibers. The myopathy is
      confined to the type II myofiber predominant muscles and is not associated with
      any pathognomonic lesions. These characteristics will provide us with a useful
      model for research in muscular dystrophy of diverse myofibers.

PMID- 15942133
TI  - The growth profiles of three types of canine distemper virus on Vero cells
      expressing canine signaling lymphocyte activation molecule.
AB  - To know growth profiles of canine distemper virus (CDV) on Vero cells stably
      expressing canine signaling lymphocyte activation molecule (Vero-DogSLAMtag; Vero
      DST cells), the propagation of three strains of CDV was tested in Vero-DST cells
      in comparison with parental Vero cells. Strain MD77 could grow well in both cell
      lines, but demonstrated no syncytium formation or indistinguishable rounding
      cytopathic effects (CPE) in Vero cells. Strains Onderstepoort and KDK-1 also grew
      well in Vero-DST cells with apparent syncytium CPE, while they grew less or no
      efficiently, respectively, in Vero cells. All three CDV strains demonstrated the
      peak titers, in Vero-DST cells before reaching to an extensive CPE and drastic
      decrease of titers at/after full CPE. Immunohistochemistry revealed that viral
      antigens of all CDV strains were found exclusively in the syncytia in Vero-DST
      cells, while in Vero cells, viral antigen was identified in their single cells
      for strain MD77 but none for other strains. Thus, every strain of CDV could grow
      well in Vero-DST cells and behaved differently against Vero cells. These results
      would be of practical value for workers of CDV because 1) In Vero-DST cells, by
      observation of distinct syncytium CPE, the highest titer or the best growth of
      virus could be identified; 2) In Vero cells, various CDV strains could be readily
      classified after propagation in Vero-DST cells.

PMID- 15942134
TI  - Ultrasonic measurement of fetal parameters for estimation of gestational age in
      Korean black goats.
AB  - The objective of this study was to determine relationship of gestational age with
      measurement of diameter of head, orbit, trunk, long and short axis of heart,
      aorta, placentome, umbilical cord and umbilical vein in Korean black goats. In
      this study, ten pregnant Korean black goats (Capra hircus aegagrus) were used.
      Pregnancy diagnosis was performed with a 5 MHz linear transducer and
      ultrasonographic scan were performed at 60, 75, 90, 105, 120 and 135 days after
      mating with a 4-9 MHz convex transducer. For accurate measurement, all fetal
      organs were measured at least 3 times. The diameter of head, orbit, trunk, long
      and short axis of heart, aorta, placentome, umbilical cord and umbilical vein
      were significantly increased with the gestational age (p<0.05). Of these
      parameters, trunk (r=0.8876; p<0.001), long axis of heart (r=0.9168; p<0.001) and
      short axis of heart (r=0.8819; p<0.001) proved to be the more effective
      measurements than other parameters, as it correlated well with gestational age.
      Results indicate that ultrasonic measurements of these parameters were useful
      methods to estimate gestational age in Korean black goat.

PMID- 15942135
TI  - Production and characterization of monoclonal antibodies against porcine
      interleukin-4.
AB  - Interleukin 4 (IL-4) is an important regulatory cytokine produced by activated T
      lymphocytes and mast cells, and regulates the growth and differentiation of cells
      such as B and T lymphocytes. In the present study, recombinant thioredoxin (Trx)
      porcine IL-4 (pIL-4) fusion protein was prepared by Escherichia coli (E. coli),
      and by using this protein as an immunogen, monoclonal antibodies (mAbs) against
      pIL-4 were produced to establish a basis for a research on immune responses in
      pigs. Six stable hybridoma cell lines were successfully established and specific
      binding of each mAb to recombinant pIL-4 produced by E. coli and insect cells
      infected with recombinant baculovirus was shown by enzyme-linked immunosorbent
      assay (ELISA) and/or immunoblot analysis. Isotype analyses of these mAbs revealed
      that the subclass of 5 out of 6 mAbs was IgG1 and the rest was IgG2b. Further,
      assessment of their epitopes by competition binding assay indicated that the mAbs
      obtained in this study bound to 4 different epitopes. The recombinant proteins
      and mAbs produced in this study will be useful tools for the assessment of
      porcine immune system.

PMID- 15942136
TI  - Electroretinography using contact lens electrode with built-in light source in
      dogs.
AB  - Electroretinography (ERG) is an effective method for the diagnosis of retinal
      disease. In the dog, dependable ERG recording is difficult without the use of an
      expensive device like a Ganzfeld full-field stimulator. The International Society
      for Clinical Electrophysiology of Vision has defined the standard flash stimulus
      condition (SF) and evaluation of the retina using the b/a ratio in humans. In
      dogs, evaluation using the b/a ratio has not been reported, whereas the intensity
      of SF has been defined. In this study, we performed a convenient ERG recording
      method using a contact lens electrode with a built-in light source (LED
      electrode), and confirmed SF as reported previously. ERG recordings were
      performed on 15 healthy beagle dogs under sedation. We performed bilateral ERG at
      12 different intensities after 30 min dark adaptation. After 10 min light
      adaptation, we recorded single flash cone and flicker cone response using the SF
      determined in this study. In this study, SF of 3.0 cd/m(2)/sec (6,000 cd/m(2),
      0.5 msec) resulted in b/a=2. The intensity for rod response that recorded only
      the b-wave was 0.0096 cd/m(2)/sec (80 cd/m(2), 0.12 msec). We could achieve ERG
      for each response easily and smoothly under sedation, and without general
      anesthesia. Using an LED-electrode, we could perform more quantitative and
      reproducible ERG examinations than with traditional methods. We propose that the
      b/a ratio is the most useful parameter in ERG reporting for evaluating retinal
      function.

PMID- 15942137
TI  - High susceptibility of Djungarian hamsters (Phodopus sungorus) to the infection
      with Babesia microti supported by hemodynamics.
AB  - As the comparative study was carried out on the susceptibility by the pursuit of
      parasitemia among the Djungarian, Syrian, and Chinese hamsters as well as BALB/c
      mice infected with the Syrian hamster-adapted Babesia microti strain, and
      Djungarian hamsters showed the highest parasitemia among them. Then, the other
      hematological parameters were pursued in the Djungarian hamsters infected with
      the hamster-adapted B. microti strain. Remarkable symptoms observed were
      hemoglobinuria clinically, anemia hematologically, and splenomegaly
      macroscopically during all over the observation period for 24 weeks post
      infection (PI). Parasitemia began to rise at 2 weeks and peaked at 4 weeks PI.
      After that, parasitemia decreased gradually but was maintained with a level of
      about 10% on average until 24 weeks PI at the end of the experiment. A decrease
      in the RBC count, Hb, and PCV, and an increase in the reticulocyte and WBC counts
      due to the development of immature neutrophils, lymphocytes and monocytes were
      recognized together with a rise of parasitemia. The hamsters had macrocytic
      hypochromic anemia due to the increase of MCV and the decrease of MCHC in the
      growth phase of the parasite. It was considered that the Djungarian hamsters will
      be useful for the infection examination, isolation, maintenance, and passage of
      B. microti in laboratory.

PMID- 15942138
TI  - Induction of interferon-gamma (IFN-gamma) and T helper 1 (Th1) immune response by
      bitter gourd extract.
AB  - Mice were inoculated intraperitoneally wih 34 different types of vegetable
      juices, and interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were measured
      as markers for the induction of Th1 and Th2 cells, respectively. Serum IFN-gamma
      level was markedly increased in mice inoculated with bitter gourd (Momordica
      charantia) juice, but IL-4 levels were not increased with any of the 34 vegetable
      juices. Testing of the various components of bitter gourd, including peel, pulp,
      and seed, showed that the pulp induced the highest levels of IFN-gamma. Trial
      immunogen including the heat extract of the pulp induced specific IgG(2a)
      antibody of the mice serum inoculated with this immunogen. These results
      demonstrate that bitter gourd pulp induced IFN-gamma production and show its
      promise as a means of effective immunostimulatory therapy specific for Th1 cells
      and IFN-gamma production.

PMID- 15942139
TI  - Molecular cloning of the canine c-Met/HGF receptor and its expression in normal
      and regenerated liver.
AB  - The c-Met proto-oncogene is the receptor for hepatocyte growth factor (HGF),
      which is a member of the tyrosine kinase family. Activation of the HGF/c-Met
      signal pathway leads to cell proliferation, motility, regeneration, and
      morphogenesis. In this study, the complete nucleotide sequence of complementary
      DNA (cDNA) of canine c-Met was cloned, and its distribution was determined in
      tissues. The canine c-Met cDNA clone had an open reading frame of 4419 bp that
      encoded a putative polypeptide of 1383 amino acids. The c-Met mRNA was expressed
      in a variety of canine tissues including peripheral blood mononuclear cells
      (PBMC), bone marrow, liver, kidney, lung, stomach, uterus, testis, thymus, lymph
      node, small intestine, colon, adrenal gland, thyroid gland, heart, muscle, skin,
      pancreas, ovary, prostate, spleen, fat, cerebrum, and cerebellum. In addition,
      the c-Met mRNA expression in normal and regenerated liver was examined. The
      levels of the mRNA increased 2-fold in regenerated liver compared to that found
      in normal liver, indicating that c-Met is involved in various functions including
      remodeling of canine hepatocytes.

PMID- 15942140
TI  - Suppressive effect of deoxynivalenol, a Fusarium mycotoxin, on bovine and porcine
      neutrophil chemiluminescence: an in vitro study.
AB  - We evaluated the immunotoxicity of deoxynivalenol (DON), a Fusarium mycotoxin, on
      bovine and porcine neutrophils in vitro by using two function parameters, luminol
      dependent chemiluminescence and random migration under agarose. A 2-hr DON
      treatment suppressed the chemiluminescence of bovine and porcine cells by 42% and
      35% (on average) at 10(-5)M, and by 19% and 26% at 10(-6)M. Slight suppression
      was observed at concentrations lower than 10(-6)M. However, after an 18-hr DON
      treatment, random migration of neutrophils of both species remained unaffected,
      even at the highest concentration (10(-5)M). Although further extensive studies
      are needed, to our knowledge this is the first study to have revealed in vitro
      that DON can affect neutrophil function.

PMID- 15942141
TI  - Enzyme-linked immunosorbent assay for detection of canine chromogranin A by use
      of immunological cross-reactivity of rabbit anti-bovine chromogranin A antibody.
AB  - Bovine and canine chromogranin A were extracted and purified from each specie's
      adrenal glands. Isolated bovine 70 kDa protein showed 100% identity to bovine CgA
      reported previously, whereas isolated canine 68 kDa protein showed 83.3% identity
      to bovine CgA by the NH(2)-terminal amino acid sequence analysis. Rabbit antibody
      to purified bovine protein (CgA) was found to immunologically cross-reacted with
      purified canine protein (CgA). In sandwich ELISA with anti-bovine CgA,
      concentration-dependent curves were obtained ranging from 0.3 to 20 mug/ml for
      canine CgA. From these findings, sandwich ELISA with anti-bovine CgA is found to
      be useful to determine the concentration of canine CgA.

PMID- 15942142
TI  - Molecular cloning and sequences of interleukin-10 in the Djungarian (Phodopus
      sungorus), Chinese (Cricetulus griseus), and Syrian (Mesocricetus auratus)
      hamster.
AB  - Interleukin 10 (IL-10) genes of Djungarian, Chinese, and Syrian hamsters were
      cloned. The clones of IL-10 consisted of 537 bp nucleotides and 178 amino acids
      in full length, and the nucleotide and amino acid sequences exhibited a high
      degree of homology with those of the mouse and human. Since the number and
      position of signal sequences, N-glycosylations and cysteine sites in the IL-10
      amino acid sequences of the hamsters were the same as those of the mouse, we
      suggest that the IL-10 molecular structures of the hamster are closer to that of
      the mouse than human.

PMID- 15942143
TI  - Expression of feline interferon-alpha subtypes in Esherichia coli, and their
      antiviral activity and animal species specificity.
AB  - Two kinds of FeIFN-alpha consisting of 166 amino acids (aa) and 171 aa were
      expressed in Escherichia coli, and the purified proteins were tested for
      antiviral activity on homologous and heterologous animal cells. Crude FeIFN
      induced in feline cells revealed antiviral activity on both homologous and
      heterologous animal cells. In contrast, both types of recombinant FeIFN-alpha
      revealed antiviral activity only on the feline cells. All of the FeIFN-alpha
      subtypes showed high activity to vesicular stomatitis virus, and the three
      species of feline viruses belonging to different families.

PMID- 15942144
TI  - Smoking prevalence and attitudes toward tobacco among student and staff nurses in
      Niigata, Japan.
AB  - The present study investigated smoking prevalence and attitudes toward smoking in
      student and staff nurses, and activities to promote tobacco intervention by staff
      nurses. A total of 743 student nurses in 2 colleges and one university and 490
      staff nurses in the university hospital in Niigata, Japan participated in the
      study and filled in self-administered anonymous questionnaires focused on smoking
      habits, attitudes toward smoking, and activities to promote tobacco intervention.
      The smoking prevalence among student nurses was 6% and increased with the year of
      study, whereas that of among staff nurses was 16% and increased by employment up
      to 3-5 years. Almost half of the student nurse smokers started the habit before
      admission to higher education facilities, and more than half of staff smokers
      also started smoking in their school years, in high school or college. Nicotine
      dependence, as defined by over 11 cigarettes per day and the first cigarette
      within 30 min after getting up, was high in smokers who started smoking before
      admission to college or university, but not in those who took up the habit
      thereafter. Thirty-six percent of student nurses and 25% of staff nurses agreed
      with the statement that "nurses should not smoke." Only 12% of staff nurses were
      involved in anti-tobacco interventions routinely, partly due to lack of broad
      knowledge and the necessary skills. Greater efforts are needed as a high priority
      to educate student and staff nurses systematically and comprehensively about the
      range of tobacco interventions available in Japan.

PMID- 15942145
TI  - Strategies for improving pediatric services in Japan.
AB  - The shortage of pediatricians and emergency medical care for children is an issue
      of great concern in Japan. This study attempts to identify the problems in
      children's medical care and their causes. With multiple secondary data sources,
      we found that over 80% of outpatient pediatric services were provided by clinics,
      that over 95% of clinics were closed on holidays, Sunday, and Saturday night,
      that among the children's illnesses respiratory ailments were dominant and were
      generally acute and required immediate treatment or consultation, and that the
      revenue rates from providing services for children were lower than those for
      adults. That fewer clinics are open on Saturday night, Sunday and holidays, and
      workday evenings may be the main reason why it is difficult for children to find
      pediatric services outside of normal working hours. Lower revenue rates may be
      one of the key reasons why the number and rate of clinics and hospitals providing
      pediatric services continue to decline, and fewer physicians are willing to
      provide services for children. The findings in this research would provide
      important information of multiple dimensions for the governments to make efforts
      to improve pediatric services in Japan. Our proposition is to prompt pediatric
      specialists and internists who can treat pediatric cases in clinics to provide
      pediatric service systematically and alternatively at night, and to adjust the
      fee-for-service scales of pediatric services.

PMID- 15942146
TI  - Repeated stress suppresses interferon-gamma production by murine intestinal
      intraepithelial lymphocytes.
AB  - Intestinal intraepithelial lymphocytes (IEL), one of the major effector
      components in the mucosal immune system, are phenotypically and functionally
      distinct from thymic and peripheral T cells. To investigate the effect of
      repeated stress on the number and function of IEL, we exposed male C3H/HeN mice
      to mild electric foot shock for 30 min/day for 5 consecutive days. Immediately
      after the final foot shock stress, the blood, spleen, thymus and small intestine
      of each of the mice were obtained. As a functional measure, we evaluated
      interferon (IFN)- gamma production by IEL, since IFN-gamma is a key
      immunomodulating cytokine in mucosal immune responses. Serum corticosterone level
      was elevated immediately after foot shock stress. There were no significant
      changes in the number of whole IEL and CD3+ IEL subsets after the stress. In
      contrast, the stress led to a significant decrease in the total number of
      thymocytes, particularly the reduction in the number of CD4+CD8+ thymocytes.
      Thymocytes expressed the highest level of intracellular glucocorticoid receptor
      (GR), followed by splenocytes and IEL. The foot shock stress induced a marked
      suppression of IFN-gamma production by IEL, when stimulated with immobilized anti
      CD3 monoclonal antibody. Furthermore, corticosterone suppressed the IFN-gamma
      production by cultured IEL, which was prevented by Mifepristone (RU486), a GR
      antagonist. In summary, repeated foot shock stress did not alter the numbers of
      IEL and CD3+ IEL subsets, but suppressed IFN-gamma production by IEL, which was
      probably mediated by the elevated corticosterone. We therefore propose that
      stress influences host defense by suppressing the production of IFN-gamma in IEL.

PMID- 15942147
TI  - Music can enhance exercise-induced sympathetic dominancy assessed by heart rate
      variability.
AB  - Many studies have been conducted on physiological responses of music, yielding
      controversial results. In the present study, we examined whether music affects
      the exercise-induced changes in the autonomic nervous system activity in twelve
      healthy female college students. On the first day, the subjects were asked to
      rest, exercise, and then rest for 15 min, respectively. On the second day, they
      were asked to rest with music, exercise, and then rest with music for 15 min,
      respectively. Heart rate variability was measured for the pre- and post-exercise
      periods. Music was given according to subjects' preferences using a vibroacoustic
      apparatus (body sonic system), i.e. a chair on which subjects laid and felt low
      pitch sounds by their body in addition to listening music. With music, ratio of
      low frequency to high frequency component of heart rate variability (LH/HF) was
      significantly increased after exercise as compared with before exercise (p <
      0.01). By contrast, the changes in LH/HF were not significant without music (p >
      0.05). It is suggested that after exercise in which sympathetic nerve activity is
      dominant, preferred music synchronizes with the activated physical response,
      further promoting the response and increasing sympathetic nerve activity.
      Combining music with exercise is therefore not only enjoyable in terms of mood
      but also may promote physiological excitation and enhance physical activation.

PMID- 15942148
TI  - Decreased serum lipoprotein levels as a guide for clinical severity in patients
      with idiopathic dilated cardiomyopathy.
AB  - Hyperlipidemia is a cardiovascular risk factor. In patients with idiopathic
      dilated cardiomyopathy (IDC), prognostic roles of endogenous lipoproteins are not
      fully clarified. It has been known that there is a direct relationship between
      the levels of cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukin
      6 [IL-6]) and deteriorating functional classes of heart failure and mortality.
      The present study compared the levels of circulating TNF-alpha, IL-6,
      lipoproteins, and apolipoproteins in patients with stable IDC (n = 28) with those
      of patients with unstable IDC (n = 26) and controls (n = 24). Mean serum total
      cholesterol (TC) was significantly lower in stable IDC patients than controls (p
      < 0.05). In unstable IDC patients, mean serum TC was also lower than controls but
      not statistically significant. The IDC patients had significantly higher
      concentrations of IL-6 and TNF-alpha than the controls (p < 0.01). Serum IL-6 and
      Apo AI levels were significantly different between stable and unstable IDC
      patients (p = 0.021 and p = 0.012, respectively). Increased levels of IL-6 were
      associated with decreased levels of TC (r = -0.266, p = 0.019), LDL-C (r = 
      0.376, p = 0.001) and apolipoprotein AI (apo AI) (r = -0.495, p < 0.001) in all
      IDC patients. TNF-alpha was also inversely related to apo AI (r = -0.455, p <
      0.001) and LDL-C (r = -0.364, p = 0.001) in all patients. Thus, elevated serum
      levels of cytokines in patients with IDC are associated with decreased
      lipoprotein concentrations, which may indicate impaired prognosis.

PMID- 15942149
TI  - Elevated plasma homocysteine concentrations in severe preeclampsia and eclampsia.
AB  - Homocysteine is an essential amino acid required for the growth of cells and
      tissues in the human body. Maternal hyperhomocysteinemia is associated with a
      number of placenta-mediated diseases such as preeclampsia. The aim of this study
      was to evaluate the plasma level of homocysteine and its association with
      severity of preeclampsia. A case-control study was performed with 32 mild
      preeclamptic patients, 25 severe preeclamptic patients, 16 eclamptic patients and
      34 controls. Maternal plasma homocysteine concentration was measured
      prospectively at antenatal period by high-performance liquid chromatography.
      There were no significant differences in demographic characteristics between the
      study and control groups. Mean plasma levels of homocysteine in women with severe
      preeclampsia (16.7 +/- 10.1 micromol/l, mean +/- S.D., n = 25) and eclampsia
      (16.5 +/- 9.6 micromol/l, mean +/- S.D., n = 16) were significantly higher than
      those in mild preeclampsia (7.7 +/- 2.4 micromol/l, mean +/- S.D., n = 32) and
      controls (6.7 +/- 1.6 micromol/l, mean +/- S.D., n = 34) (p < 0.0001). It should
      be noted that plasma levels of homocysteine are not significantly different
      between mild preeclampsia and controls. In conclusion, plasma homocysteine
      concentrations are increased in severe preeclampsia and eclampsia, but not in
      mild preeclampsia.

PMID- 15942150
TI  - Exogenous leptin increases lipid peroxidation in the mouse brain.
AB  - Leptin, a hormone produced by the adipose tissues, reduces appetite and food
      intake, and increases energy expenditures by sending signals to the brain cells.
      As human obesity is associated with hyperleptinemia and increased systemic
      oxidative stress, we investigated whether leptin affects lipid peroxidation and
      antioxidant status in the brain. Leptin was intraperitoneally administered to
      adult male BALB/c mice (n = 6) at a dose of 40 mug/animal for 5 days, while
      control mice (n = 6) received phosphate buffered saline. All animals were
      decapitated one hour after the last injection, and the brain tissues were
      removed. Total brain tissues were homogenized with phosphate buffered saline.
      Lipid hydroperoxide and glutathione levels were measured by enzyme immunoassays.
      Data were statistically analysed by using Mann Whitney's U-test. Lipid
      hydroperoxide levels were significantly higher in the brain tissue of leptin
      treated mice (3.44 +/- 0.36 nmol/g tissue, mean +/- S.E.M.) than those of the
      control mice (2.20 +/- 0.38 nmol/g tissue, p < 0.01). In contrast, leptin-treated
      mice had significantly lower glutathione levels in the brain tissue compared to
      the control (12.97 +/- 1.32 and 17.91 +/- 0.82 nmol/g tissue, respectively, p <
      0.05). These results indicate that exogenous leptin increases lipid peroxidation
      and inhibits antioxidant system in the mouse brain. We therefore suggest that
      leptin may augment oxidative stress in the brain.

PMID- 15942151
TI  - Priming effect of misoprostol on estrogen pretreated cervix in postmenopausal
      women.
AB  - Misoprostol, which is a prostaglandin E1 analogue, is effectively used in
      cervical priming in women both for labor induction and for gynecological
      procedures. Although its efficacy is well documented in reproductive age women,
      during postmenopausal period this efficacy is limited probably due to estrogen
      deficit. Our objective is to evaluate if estrogen deficit in postmenopausal women
      is important for the effect of misoprostol on cervical ripening before diagnostic
      procedures. In this study, 45 patients were randomly allocated to estrogen or
      placebo group. The study group received local estrogen cream and other group
      received chlindamycine phosphate cream as placebo. The patients were given oral
      misoprostol 24 and 12 hours before the procedure for uterine cavity evaluation.
      Cervix was dilated by using Heagar dilator up to 6 mm. Data were analyzed by
      Student t-test, Mann-Whitney's U-test, chi-square test and paired samples t-test
      where appropriate. Basal cervical widths for the estrogen and placebo groups were
      4.4 +/- 0.7 and 3.7 +/- 0.7 mm, respectively (p < 0.01). Mean time required for
      dilatation of cervix was 44.4 +/- 16.2 seconds for the estrogen group and 61.4 +/
      18.3 seconds for the placebo group (p < 0.01). As a conclusion, misoprostol
      treatment alone is not effective to get cervical priming in postmenopausal women,
      and as shown in our study, pretreatment with local estrogen overcome the failure.
      To get a beneficial effect of misoprostol on cervical ripening, estrogenic
      activity is necessary and when pretreated with local estrogen, misoprostol
      ameliorates cervical priming in postmenopausal women.

PMID- 15942152
TI  - Is there a link between nickel allergy and coronary stent restenosis?
AB  - Although many patients with coronary artery disease are being treated by coronary
      stents, in-stent restenosis is the major limitation of percutaneous coronary
      stenting procedures. Most stents are made of stainless steel, and that, allergic
      reactions to nickel ions released from coronary stainless-steel stents may be one
      of the triggering mechanisms for in-stent restenosis. We aimed to evaluate the
      relationship between in-stent restenosis and nickel allergy in a prospective
      study. For this purpose, we applied epicutaneous patch test for nickel in 43
      patients who had undergone elective intracoronary stent placement for stable
      angina pectoris in the day following stent placement and evaluated the presence
      of nickel allergy. Control angiography was performed at 6 months to determine in
      stent restenosis. Three (6.9%) patients had allergic reaction to nickel and 16
      (37%) patients had developed in-stent restenosis. One of the 3 patients with
      nickel allergy had diffuse in-stent restenosis and the others not. The present
      study therefore does not support the proposed relationship between nickel allergy
      and development of in-stent restenosis in patients having stainless steel stents.
      Large scale studies are needed to reach a final conclusion.

PMID- 15942153
TI  - Zinc may protect remote ocular injury caused by intestinal ischemia reperfusion
      in rats.
AB  - Remote organ injury represents the oxidative damage, which occurs in various
      organs away from the tissues exposed to ischemia-reperfusion insult.
      Hypothesizing that the eye may be susceptible to this type of tissue damage, we
      investigated the effect of splanchnic ischemia-reperfusion on the chorio-retinal
      tissue in Sprague-Dawley rats. Four groups, each consisting of 10 male rats, were
      designed for the study. Ischemia-reperfusion was introduced by clamping superior
      mesenteric artery for 1 hour, followed by reperfusion for 90 min (IR group). In
      another group, the same operation was performed except that zinc aspartate (50
      mg/kg) was given intra-peritoneally 15 min before the opening of the clamp (Zn-IR
      group). As control (sham group), the abdomen was opened without any intervention
      on superior mesenteric artery. The other group was given Zn after opening of
      abdomen without any intervention on superior mesenteric artery (Zn-sham group).
      After the choroid and the retina were dissected from the eye, malondialdehyde,
      superoxide dismutase, catalase and nitric oxide (NO) were measured in the
      collected eye tissues. We found that the levels of malondialdehyde, an indicator
      for lipid peroxidation, were higher in the chorio-retinal tissue of IR group
      compared to Zn-IR, Zn-sham or sham group (p < 0.05). The oxidative stress in Zn
      IR group was not higher than that of sham group. Treatment with zinc decreased NO
      levels but had no noticeable effect on the level of antioxidant enzymes. Our
      study indicates that remote organ injury is induced in the eye during splanchnic
      ischemia-reperfusion and that zinc may be beneficial to ameliorate remote ocular
      injury.

PMID- 15942154
TI  - Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in
      patients carrying identical SBDS mutations.
AB  - Shwachman-Diamond syndrome (SDS) is a rare hereditary disorder characterized by
      pancreatic exocrine insufficiency, bone marrow dysfunction and skeletal changes.
      Recently, the cause of SDS was identified as mutations of Shwachman-Bodian
      Diamond syndrome gene (SBDS) and most mutations are caused by gene conversion
      between SBDS and its highly homologous pseudogene. Clinical variations especially
      in skeletal and bone marrow abnormalities are well known in this syndrome. To
      study the relationship between SBDS mutation and its clinical features, we
      analyzed 9 Japanese patients including one sibling and detected the three
      different SBDS mutations in 7 patients: a mutation that disrupts the donor splice
      site of intron 2, deletes 8 bp of the exon 2 and produces premature termination
      (258+2 T > C), a dinucleotide change that replaces a lysine at 62 nd amino acid
      to a termination codon (183-184 TA > CT), and a 4-bp deletion that causes
      premature termination by frameshift (292-295 delAAAG). The 5 patients represent
      compound heterozygotes of the 258+2 T > C and 183-184 TA > CT mutations. One
      patient is a compound heterozygote of the 258+2 T > C and 292-295 delAAAG
      mutations, and in the remaining one case only a 258+2 T > C mutation could be
      detected. Thus, the 258+2 T > C and 183-184 TA > CT mutations are prevalent among
      Japanese patients. No mutations were found in two cases, despite the clinical
      features. Of the 7 patients with SBDS mutations, persistent hematologic
      abnormalities and skeletal changes were not observed in 3 and 2 patients,
      respectively. Notably, clinical variations are present even among the patients
      with the identical genotype: compound heterozygotes of the 258+2 T > C and 183
      184 TA > CT mutations. Further study will be required to explain the clinical
      heterogeneity.

PMID- 15942155
TI  - Successful conservative treatment of a cesarean scar pregnancy with uterine
      artery embolization.
AB  - Ectopic pregnancy developing in a previous Cesarean section scar is rare and is
      associated with catastrophic complications, such as uterine rupture and
      uncontrollable bleeding, which may lead to loss of the uterus. The operative
      treatments that have been reported for cesarean scar pregnancy are dilatation and
      curettage and excision of trophoblastic tissues using either laparotomy or
      laparoscopy. Recently, conservative treatment of scar pregnancy with locally
      and/or systemically administered methotrexate (MTX) has been reported. However,
      recent reports demonstrated that cases treated with MTX sometimes required
      laparotomy later because of excessive bleeding. In this series of cases we have
      demonstrated that viable cesarean scar pregnancies can be treated safely by
      selective transarterial embolization in combination with subsequent dilatation
      and curettage and local or systemic injections of MTX. In these three cases,
      uterine artery embolization proved to be a useful procedure for preventing
      uncontrollable bleeding and unnecessary uterine loss.

PMID- 15942156
TI  - Squamous papillomatosis of the bilateral nasal cavities.
AB  - The term "papillomatosis" indicates the tendency towards multicentricity and
      recurrence that these tumors exhibit (Snyder et al. 1972). A typical squamous
      papilloma arises from the nasal vestibule and is characterized by the epithelial
      proliferation growing an exophytic manner. We report a rare case of squamous
      papillomatosis of the bilateral nasal cavities. A 65-year-old man presented with
      a 2-year-history of bilateral nasal obstruction. Computed tomographic (CT) scans
      revealed a soft density mass in the bilateral nasal cavities and ethmoid sinuses.
      Because the tumors were limited to the nasal cavities and anterior ethmoid
      sinuses, total removal of the tumors was performed endoscopically. On the basis
      of the clinicopathological findings, the tumors were diagnosed as squamous
      papillomas. His post-operative course was uneventful, and he is currently free
      from disease 13 months after surgery. Nasal papillomas usually arise from the
      unilateral nasal cavity or paranasal sinus. While some cases of inverted
      (inverting) papillomas arising from the bilateral nasal cavities have been
      reported, bilateralism of the nasal squamous papillomas is quite rare. Diagnosis,
      clinical behavior and treatment of squamous papillomatosis of the bilateral nasal
      cavities are reviewed.

PMID- 15942157
TI  - Primary clear cell adenocarcinoma of the peritoneum.
AB  - We report on a very rare case of peritoneal clear cell adenocarcinomas. A 49-year
      old Japanese woman underwent hysterectomy and bilateral salpingo-oophorectomy for
      endometrial endometrioid adenocarcinoma grade III, which was composed of
      undifferentiated carcinoma cells (98%) and tubular carcinoma cells (2%). No clear
      cell adenocarcinoma elements were noted in this tumor. Two peritoneal cystic
      tumors were detected by imaging modalities around the stomach and spleen, 15
      months and 21 months after the follow-up period of the endometrial carcinoma,
      respectively. These two tumors were surgically resected. They were cystic tumors
      encapsulated by fibrous capsules and showed the same morphologies. They showed
      proliferation of carcinoma cells arranged in solid nest, tubular, and papillary
      patterns. They showed clear cytoplasm positive for periodic acid-Schiff stain,
      hobnail cells, and occasional hyaline globules. The morphologies fulfilled the
      criteria of clear cell adenocarcinoma. The morphologies and immunohistochemical
      findings of the two peritoneal clear cell adenocarcinomas were different from
      those of endometrial carcinoma. We believe that the two clear cell
      adenocarcinomas are not metastatic lesions from the endometrial carcinoma of the
      uterus, and that they are primary clear cell adenocarcinomas of the peritoneum.
      Our case was characterized by cyst formations and encapsulation in addition to
      the common histological features of clear cell adenocarcinoma of the uterus and
      ovary.

PMID- 15942158
TI  - A new technique for superior hypogastric plexus block: the posteromedian
      transdiscal approach.
AB  - Superior hypogastric plexus block has been advocated for the treatment of cancer
      related pelvic pain. Neurolysis is usually established using the classical
      posterolateral approach in the prone position, in which correct placement of the
      needle is sometimes difficult due to vertebral anatomy and the patient's
      inability to lie prone. We describe an alternative posteromedian transdiscal
      approach under fluoroscopic guidance for the treatment of intractable pelvic pain
      in three patients, in whom the classical approach was not possible. The L5-S1
      interdiscal space was identified with fluoroscopy. The needle was then introduced
      through the disc and advanced under lateral fluoroscopic control. After verifying
      correct needle placement, neurolysis was performed with 8 ml of 10% phenol
      solution. All patients had significant pain relief immediately after the block,
      lasting from 6 to 12 months, and their pain severity scores and opioid
      consumption were reduced by more than 50%. There were no complications such as
      discitis, disc rupture or nerve injury. Since this new posteromedian transdiscal
      approach provides easy access to the superior hypogastric plexus with a single
      puncture and with any patient position, it may be an alternative to the classical
      approach.

PMID- 15942159
TI  - Effect of an oat bran-rich supplement on the metabolic profile of overweight
      premenopausal women.
AB  - BACKGROUND/AIMS: A healthy diet is a key factor in the prevention of
      cardiovascular disease, the leading cause of death for women in industrialized
      countries. In this regard, soluble fibers may have beneficial effects on the
      plasma lipoprotein/lipid profile. The objective of the present study was to
      investigate the plasma lipoprotein/lipid response to dietary fibers in overweight
      premenopausal women within a randomized controlled trial. METHODS: Following a 2
      week run-in phase, 34 premenopausal women (age: 22-53 years) were randomly
      assigned either to the control group (no supplement) or to the treatment group,
      which received 2 oat bran-enriched muffins per day (28 g/day of oat bran) during
      4 weeks. RESULTS: Supplementation with oat bran had a beneficial effect on plasma
      HDL-C levels. Indeed, compared to the control group (n = 16), a mean increase in
      plasma HDL-C levels of 11.2% was observed in women eating the oat bran supplement
      (n = 18) (p = 0.01), whereas the total cholesterol/HDL-C ratio decreased by 7.0%
      (p = 0.002). Results were similar after adjustment for age, apo E genotype and
      weight change. CONCLUSION: These results suggest that oat bran-rich foods have
      beneficial effect on the metabolic profile of overweight women. Integration of
      these foods as part of a healthy diet may, therefore, improve the cardiovascular
      risk profile of women.

PMID- 15942160
TI  - Relationship of coffee consumption with risk factors of atherosclerosis in rats.
AB  - AIMS: In experimental animals we investigated the relationship of coffee
      consumption with risk factors of atherosclerosis such as cholesterol,
      homocysteine, oxidative stress and inflammatory cytokines. METHODS: Forty-eight
      male Wistar rats were assigned to 3 treatment groups (a control diet group, 0.62%
      coffee diet group, and 1.36% coffee diet group), and animals were maintained on
      the experimental diets for 140 days. RESULTS: Coffee diets led to an increase in
      the caffeine concentration to 0.53 +/- 0.11 and 1.77 +/- 0.22 microg/ml,
      respectively, although caffeine in serum was not detected in rats fed the control
      diet. It also led to slightly increased total serum levels of homocysteine and
      cholesterol, but no significant differences were found between the control and
      coffee diet groups. Coffee intake did not affect the production of IL-6 and TNF
      alpha induced by LPS, which contributes to the atheroma-promoting effect of
      recurrent bacterial infection. Regarding the biomarkers of oxidative stress, the
      serum level of 15-isoprostane F(2t), which was significantly increased by LPS
      injection, was not altered by coffee intake. In contrast, urinary 8-hydroxy-2
      deoxyguanosine was significantly increased in the coffee diet groups (p < 0.05).
      On the other hand, serum glutathione peroxidase (GPx) activity tended to decrease
      in the coffee groups compared with the control group, but no significant
      difference was found between the control and coffee diet groups. Interestingly, a
      significant negative correlation was observed between GPx activity and
      homocysteine levels in the sera from control and coffee diet groups (r = -0.403,
      p < 0.05). CONCLUSIONS: This report is the first animal study on the relationship
      of coffee consumption with risk factors for atherosclerosis. From these results,
      we conclude that moderate coffee intake is not a risk factor for atherogenesis.

PMID- 15942161
TI  - Variation in stomatopod (Gonodactylus smithii) color signal design associated
      with organismal condition and depth.
AB  - In interactions, many tropical stomatopod species display conspicuous colored
      body spots that can communicate information about the sender's state (e.g., sex,
      aggressiveness, etc.). Species inhabiting a variety of depths experience large
      differences in illumination spectrum and intensity due to filtering of light by
      water and its constituents. Stomatopod spectral sensitivity is known to vary
      phenotypically with changes in light environment (associated with depth) that
      potentially affects the detection of color signals. Animals collected at
      different depths also have different body coloration. This study examines how
      spectral differences in colored body spots vary with organismal condition and
      models the effects of changing body coloration, light environment, and spectral
      sensitivity on the detection of color signals in a gonodactyloid species,
      Gonodactylus smithii. Of the seven conspicuous color spots that were measured in
      G. smithii, three had spectral differences that correlated with sex, aggression,
      and female reproductive state. A model of color detection in G. smithii indicates
      that longer-wavelength spectral content was affected most by varying body
      coloration and light conditions. Most color signals were perceived similarly both
      by shallow- and by deep-adapted photoreceptor sets over a range of depths (1-13
      m). Eye spot ('meral spot') color detection also was invariant over the same
      depth range in shallow- and deep-adapted, long-wavelength receptors, but deep
      adapted receptors continued to maintain a consistent detection of these spots
      down to 18 meters. These results suggest that meral spot coloration may have
      evolved as a constant signal when viewed by conspecifics from various depths.

PMID- 15942162
TI  - Cyto- and chemoarchitecture of the cortex of the tammar wallaby (Macropus
      eugenii): areal organization.
AB  - We have examined the cyto- and chemoarchitecture of the isocortex of a
      diprotodontid marsupial, the tammar wallaby (Macropus eugenii), using Nissl
      staining in combination with enzyme histochemical (acetylcholinesterase - AChE,
      NADPH-diaphorase - NADPHd, cytochrome oxidase) and immunohistochemical (non
      phosphorylated neurofilament - SMI-32) markers. The primary sensory cortex showed
      distinctive patterns of reactivity in cytochrome oxidase, acetylcholinesterase
      and NADPH diaphorase. For example, in AChE material, S1 showed a heterogeneous
      appearance, with regions exhibiting a double layer of AChE activity (layers II
      and IV) adjacent to poorly reactive regions. In NADPHd preparations, activity in
      S1 was strongest in layers I to IV although, as in AChE material, there were
      consistent patches of reduced NADPHd activity which corresponded to poorly
      reactive regions in the AChE sections. Each of the primary sensory areas of the
      isocortex showed a different pattern of distribution of SMI-32+ neurons. In V1,
      SMI-32+ neurons were distributed in two layers (III and V) throughout the
      tangential extent of that region. In S1, SMI-32+ neurons were concentrated in
      layer V, but large and discrete patches within S1 had additional SMI-32+ neurons
      in layer III. In primary auditory cortex there was a dense band of SMI-32+
      neurons in layer V, with only occasional labeled pyramidal neurons in layer III.
      In the secondary sensory areas (V2 and S2) SMI-32+ neurons were either
      distributed in layers III and V (V2) or solely within layer V (S2). The
      tangential and laminar distribution of Type I reactive NADPH diaphorase neurons
      in the tammar wallaby cortex was more like that seen in eutheria than in
      polyprotodontid metatheria.

PMID- 15942163
TI  - Experimental intrauterine growth retardation in the rat causes a reduction of
      pancreatic B-cell mass, which persists into adulthood.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the
      possibility that intrauterine growth retardation (IUGR) causes alterations of
      glucose tolerance, insulin secretory response to glucose, and pancreatic B-cell
      growth, and if such changes may persist into adulthood. METHODS: Pregnant rats
      were operated on day 16 of pregnancy ad modum Wigglesworth to induce IUGR.
      Operated rats gave birth to viable offspring but litter size was reduced. The
      mothers nursed their pups, which were subsequently weaned and reared to an age of
      3 months in apparent good health. RESULTS: At 1 day of age, IUGR pups were 10%
      lighter than control newborns whose mothers had been subjected to a sham
      operation. Pancreatic B-cell mass and insulin content were reduced by 35-40% in
      newborn IUGR offspring. Postnatal growth did not differ between IUGR and control
      animals of either sex and the difference in body weight at birth was not apparent
      from 1 week of age and onwards. Tests performed at 3 months of age could not
      demonstrate differences in glucose tolerance between IUGR and control animals. In
      females, but not in males, the peak insulin secretory response to glucose was
      lower in IUGR animals compared to controls. In the 3-month-old rats, B-cell mass
      was reduced by 40% in male and by 45% in female IUGR rats compared to controls, a
      reduction corresponding to a similar decrease in pancreatic insulin content (male
      reduction 48%, female reduction 45%). CONCLUSIONS: In the rat, IUGR causes a
      diminution of pancreatic B-cell mass which persists into adulthood. Normal
      glucose tolerance could be maintained but it is conceivable that increasing
      demands on insulin secretion may not be met by the reduced B-cell mass and that
      impaired glucose tolerance and even diabetes would hence develop.

PMID- 15942164
TI  - Cardiopulmonary effects of chronic administration of the NO synthase inhibitor L
      NAME in the chick embryo.
AB  - BACKGROUND: Experimental observations in mammalian models suggest that
      endothelial nitric oxide (NO) synthase (NOS) content and activity are decreased
      in persistent pulmonary hypertension of the newborn. OBJECTIVES: To test the
      hypothesis that disruption of NO signaling in the developing chick embryo lung
      may contribute to pulmonary hypertension. METHODS: We analyzed pulmonary arterial
      reactivity and structure and heart morphology of 19-day chick embryos (incubation
      time 21 days) that received a daily injection of the NOS inhibitor Nomega-nitro-L
      arginine methyl ester (L-NAME, 20 mug per gram egg) or vehicle from day 12 until
      day 18. RESULTS: Exposure to L-NAME did not affect embryonic survival or body
      mass of the embryos. The contractile responses to KCl, endothelin-1, the
      thromboxane A2 mimetic U46619, noradrenaline, and electrical-field stimulation
      were not affected by exposure to L-NAME. In contrast, in ovo L-NAME exposure
      reduced the sensitivity of pulmonary arteries to acetylcholine (pD2: 6.53 +/-
      0.14 vs. 6.96 +/- 0.13; p < 0.05) and this effect was reversed by the NOS
      substrate L-arginine. Relaxations induced by sodium nitroprusside or forskolin
      were not altered by chronic L-NAME. Pulmonary vessel density was not different,
      but the percentage medial wall area of small pulmonary arteries (external
      diameter 10-50 microm) was slightly but significantly increased in the embryos
      exposed to L-NAME. In addition, hearts of L-NAME-exposed embryos showed an
      increase in right and left ventricular wall area. CONCLUSIONS: Chronic inhibition
      of NOS produced, in the chick embryo, impairment of endothelium-dependent
      relaxation, structural remodeling of the pulmonary vascular bed and biventricular
      cardiac enlargement.

PMID- 15942165
TI  - Distribution of apolipoprotein E alleles in a Scottish healthy newborn
      population.
AB  - The different alleles of the human apolipoprotein E polymorphism, ApoE epsilon2,
      epsilon3, epsilon4, have important implications for systemic lipid metabolism,
      immunological function and for the brain in maintenance and in response to
      injury. Few studies have focussed on their role in early life. The ApoE alleles
      and genotypes were ascertained in the cord blood of 371 full-term and normal
      Scottish newborn infants using PCR methodology. The results were compared to
      previously published data for Scottish adults in late middle age. There was a
      marginally significant over-representation of epsilon4 and under-representation
      of epsilon3 alleles in healthy infants as compared with adults. Inspection of the
      individual genotypes confirms the over-representation of ApoE 4/4 and 2/4 with a
      reduction in ApoE 2/3 and 3/3 when compared with Scottish adults. Although these
      results may have occurred by chance, the ApoE epsilon4 allele may confer an
      increased risk of premature death.

PMID- 15942166
TI  - Hyperoxia with 100% oxygen following hypoxia-ischemia increases brain damage in
      newborn rats.
AB  - OBJECTIVE: To describe the effect of reoxygenation with 100% O2 as compared to
      the effect of room air in newborn rat brains after asphyxia. METHODS:
      Experimental asphyxia (carotid artery ligation followed by hypoxic exposure with
      8% O2 for 2 h) was performed on 7-day-old rats. After hypoxia-ischemia the rats
      were reoxygenated with either 100% O2 (hyperoxia group) or 21% O2 (room air
      group) for 24 h and then returned to the dam. The rats were killed 1 week after
      the experiment to study the cerebral cortex and hippocampus. RESULTS: Rats
      reoxygenated with 100% O2 post-asphyxia showed more frequency of cortical damage
      (10 of 24 rats) than those reoxy genated with room air (3 of 24 rats) (chi2 test,
      p = 0.02). CONCLUSION: We consider that hyperoxia with 100% oxygen after hypoxia
      ischemia can cause more damage in the cerebral cortex than room air in newborn
      rats.

PMID- 15942167
TI  - Assessment of the stability of an immunoadsorbent for the extracorporeal removal
      of Beta-2-microglobulin from blood.
AB  - BACKGROUND: Dialysis-related amyloidosis (DRA) is a devastating and costly
      condition that affects patients with end stage kidney disease. A key feature of
      DRA is the formation of amyloid fibrils, consisting primarily of beta2
      microglobulin. Except for kidney transplantation, conventional kidney replacement
      therapies, which are based on nonspecific mechanisms, do not adequately address
      beta2-microglobulin removal. An antihuman beta2-microglobulin single-chain
      variable region antibody fragment (scFv) was developed to confer specificity to
      beta2-microglobulin removal during hemodialysis. METHODS: The scFv was
      immobilized onto agarose and characterized for beta2m binding capacity, thermal
      stability at 37 degrees C, regeneration capacity, storage conditions, and
      sterility. RESULTS: The beta2-microglobulin binding capacity was 1.3 mg/ml scFv
      gel. The immunoadsorbent is thermally stable, can be regenerated, stored short
      term in 20% ethanol, lyophilized for long-term storage, and withstand process
      conditions similar to that of a patient's hemodialysis therapy. CONCLUSIONS: The
      results support further investigation of immobilized scFvs as a novel tool to
      remove beta2-microglobulin from blood.

PMID- 15942168
TI  - The Scandinavian stroke scale predicts outcome in patients with mild ischemic
      stroke.
AB  - BACKGROUND: The prognostic value of the Scandinavian Stroke Scale (SSS) in
      patients with mild ischemic stroke has not previously been examined. We
      investigated if differences in SSS score predicted risk of death or dependency
      within 12 months after stroke onset. PATIENTS AND METHODS: The analysis included
      353 patients with acute cerebral infarction and SSS of at least 40 points on
      admission, 157 of whom with SSS of at least 50 points. Patients with 40-49 points
      on the SSS were compared with patients with 50-58 points; and patients with SSS
      50-53 were compared to patients with 54-58 points on the SSS. Death or dependency
      was defined as 3-6 points on the modified Rankin scale (MRS), 3 and 12 months
      after stroke onset. The frequencies of death or dependency were compared between
      groups by chi2; the risk of death or dependency 1 year after stroke was
      calculated by multiple logistic regression analysis, adjusting for age, gender,
      prestroke MRS, arterial hypertension and tobacco smoking. RESULTS: The risk of
      death or dependency 1 year after stroke onset was higher in patients with SSS 40
      49 than with SSS 50-58, OR 2.0 (CI 95% 1.2-3.5). Three months after stroke, 46.5%
      of patients with SSS 40-49 were dead or dependent in comparison with 23.9% of
      patients with SSS > 49, p < 0.001. One year after stroke, 53.6% of patients with
      SSS 40-49 were dead or dependent in comparison with 30.1% of patients with SSS >
      49, p <0.001. A significant 15% difference in living in own home was observed 1
      year after stroke onset between patients with SSS 40-49 and SSS > 49. In very
      mild stroke, 32.7% of patients with SSS 50-53 were dead or dependent 3 months
      after stroke in comparison with 18.1% of patients with SSS 54-58 on admission, p
      = 0.048. CONCLUSIONS: The SSS predicts death and dependence in patients with mild
      ischemic stroke.

PMID- 15942169
TI  - MicroRNA--taking regulation of protein synthesis to another level.

PMID- 15942170
TI  - Can patients with unruptured intracranial aneurysms be treated with thrombolysis?

PMID- 15942171
TI  - Paramedic identification of stroke: community validation of the melbourne
      ambulance stroke screen.
AB  - BACKGROUND: Paramedics require an effective prehospital tool to eliminate stroke
      mimics and to assist in the identification of suitable candidates for
      thrombolytic therapy. The Faster Access to Stroke Therapies study combined two
      validated stroke assessment tools (the Los Angeles Prehospital Stroke Screen,
      LAPSS, and the Cincinnati Prehospital Stroke Scale, CPSS) to form the Melbourne
      Ambulance Stroke Screen (MASS), and performed an in-field validation by
      Australian paramedics. METHODS: Over a 12-month period, 18 paramedics
      participated in the Faster Access to Stroke Therapies study and prospectively
      collected data contained in the MASS on all stroke dispatches, and for other
      patients with a focal neurological deficit. Sensitivity and specificity analysis
      of the LAPSS, CPSS and MASS was calculated and equivalence analysis performed.
      RESULTS: Paramedics completed 100 MASS assessments for 73 (73%) stroke/transient
      ischemic attack patients and 27 (27%) stroke mimics. The sensitivity of the MASS
      (90%, 95% CI: 81-96%) showed statistical equivalence to the sensitivity of the
      CPSS (95%, p = 0.45) and superiority to the LAPSS (78%, p = 0.008). The
      specificity of the MASS (74%, 95% CI: 53-88%) was equivalent to that of the LAPSS
      (85%, p = 0.25) and superior to the CPSS (54%, p = 0.007). All patients
      misidentified by the MASS (7 strokes, 7 mimics) were ineligible for thrombolytic
      therapy. CONCLUSION: The MASS is simple to use, with accurate prehospital
      identification of stroke. It distinguishes stroke mimics, with good recognition
      of suitable patients for thrombolytic therapy.

PMID- 15942172
TI  - Lacunar infarcts: functional and cognitive outcomes at five years in relation to
      MRI findings.
AB  - BACKGROUND: There are few long-term follow-up studies of patients with lacunar
      infarcts (LIs). The purpose of this 5-year follow-up study was to assess
      functional and cognitive outcome in relation to MRI findings. METHODS: 81
      patients with a first-ever LI were followed for 5 years with respect to
      mortality, stroke recurrence, functional and cognitive outcome. T(2)-weighted MRI
      was performed at baseline and at 5 years. The presence of basal ganglia lesions
      and white matter lesions was scored according to the European Task Force rating
      scale. Functional outcome was assessed with the Oxford Handicap Scale (OHP).
      Cognition was assessed with the Mini Mental State Examination (MMSE). RESULTS:
      The 5-year mortality was 19%. Predictors for death were age (OR = 1.07, 95% CI
      1.03-1.11), ischemic heart disease (OR = 2.1, 95% CI 1.1-4.1) and impairment
      score (OR = 1.16, 95% CI 1.02-1.32). 30% of the patients had a recurrent stroke.
      Predictors for recurrent stroke were diabetes mellitus (OR = 1.7, 95% CI 1.2-7.4)
      and amount of white matter lesions (OR = 1.7, 95% CI 1.2-2.7). 36% of the
      patients were functionally dependent (defined as OHP >2). Predictors for
      functional dependency were impairment score (OR = 1.71, 95% CI 1.12-2.59), MMSE
      (OR = 0.55, 95% CI 0.33-0.91) and stroke recurrence (OR = 84, 95% CI 9.4-745).
      16% of the patients had cognitive impairment (defined as MMSE <24). Stroke
      recurrence and white matter score, but not basal ganglia score, were correlated
      to cognitive impairment. CONCLUSIONS: Many LI patients have a good functional
      outcome at 5 years. For older patients, for patients with an initial severe
      stroke, and with additional vascular risk factors, however, the prognosis is more
      severe, with an increased risk for mortality, stroke recurrence, and physical and
      cognitive decline.

PMID- 15942173
TI  - Blood Pressure, smoking and oral contraceptive control after cryptogenic stroke
      in young adults in the PFO-ASA Study.
AB  - BACKGROUND: Management of vascular risk factors is not optimal in stroke
      patients. We assessed the control of hypertension, smoking and stopping of oral
      contraceptive in 581 consecutive young cryptogenic ischemic stroke patients
      followed in the PFO-ASA study and we identified factors associated with
      inadequate management. METHODS: At each follow-up visit, blood pressure (BP),
      smoking and use of oral contraceptive were recorded. Data were analyzed at 6
      months, 1 and 2 years. Hypertension was defined as systolic BP > or = 140 or
      diastolic BP > or = 90 mm Hg, recorded in at least two follow-up visits. Current
      smoking was defined as more than one cigarette per day reported during at least
      one follow-up visit. RESULTS: During follow-up, 36% of patients were hypertensive
      and 30% were smokers. Among the 90 hypertensive patients at baseline, 60-68%
      remained with high BP and among the 278 patients who were current smokers at
      baseline, 54-58% still smoked during follow-up. Age (OR = 1.05, 95% CI 1.02
      1.08), male sex (OR = 1.42, 95% CI 0.93-2.18), body mass index > or = 27 (OR = 2,
      95% CI 1.27-3.17) and known hypertension (OR = 3.08, 95% CI 1.80-5.28) were
      significantly associated with hypertension during follow-up. Tobacco consumption
      at baseline (OR = 35.2, 95% CI, 19.3-64.2), alcohol consumption at baseline (OR =
      2.7, 95% CI 1.4-5.2) and Rankin < or = 2 (OR = 2.6, 95% CI 1.4-4.9) were
      independently associated with persistent smoking. Among the 114 women who were
      using combined estrogen-progesterone pills at baseline, 96.5% stopped.
      CONCLUSIONS: Major risk factors for stroke are poorly controlled after stroke,
      even in the context of a prospective clinical study in young adults.

PMID- 15942174
TI  - Relationship between C-reactive protein and the electrocardiographic pattern on
      admission in patients with acute coronary syndrome.
AB  - BACKGROUND: In patients with acute coronary syndrome (ACS), the prevalence of a
      primary inflammatory pathogenic component of coronary instability, as detectable
      by elevated C-reactive protein (CRP), varies considerably. The aim of the present
      study was to assess the prevalence of inflammation in patients with ACS according
      to the different electrocardiographic (ECG) patterns on admission. METHODS:
      Hundred and thirty-six consecutive patients with the diagnosis of acute
      myocardial infarction were divided in three groups according to the ECG pattern
      on admission. Group 1 included 59 patients with ST segment elevation, group 2
      included 50 patients with ST depression and/or T wave inversion and group 3
      included 27 patients with no ECG changes. CRP was measured on admission in all
      patients. For the prevalence of inflammation analysis, we used a cutoff value of
      3 mg/l. RESULTS: CRP was above cutpoint significantly more often in patients with
      ST depression and/or T wave inversion (44.1% in group 1, 70% in group 2 and 40.7%
      in group 3; p=0.009). Patients with similar ECG pattern and CRP levels above the
      cutpoint presented a poorer outcome (coronary death, myocardial infarction and
      recurrence of instability) at one-year follow-up: 54 versus 27% for group 1, 74
      versus 27% for group 2 and 45 versus 31% for group 3. CONCLUSIONS: Patients with
      ST depression and/or T wave inversion on admission exhibit a higher prevalence of
      elevated CRP than those with ST elevation or no ECG changes, suggesting an
      important heterogeneity of the role of inflammatory triggers of the clinical
      syndromes of coronary instability.

PMID- 15942175
TI  - Sizing of atrial septal defects in adults.
AB  - In a retrospective study of 51 consecutive patients undergoing transcatheter
      closure of secundum type atrial septal defects (ASDs), we examined the
      reliability of transesophageal echocardiography (TEE) prior to catheterization
      and compared the diameter with that obtained by balloon measurement during
      catheterization. The TEE diameter was 16.3+/-4.6 mm compared with 22.5+/-6.0 mm
      for the stretched diameter obtained during catheterization (p<0.001). There was
      no gender difference. The degree of left-to-right shunting correlated poorly with
      the size of the defect. We conclude that although TEE is accurate for diagnosis
      of an ASD, the measurement of its size to determine the size of the closure
      device is at best inaccurate.

PMID- 15942176
TI  - The prevalence of common cardiovascular diseases among 17-year-old Israeli
      conscripts.
AB  - BACKGROUND: There are only few reports on the prevalence of common cardiovascular
      disorders among adolescents. The previous studies focused on specific diseases,
      and screened relatively small samples. OBJECTIVE: The aim of this study was to
      define the prevalence of different common cardiovascular disorders among 17-year
      old Israeli conscripts. A comparison between the morbidity patterns of female and
      male adolescents was also performed. DESIGN: All 17-years-old Israeli nationals
      are obliged by law to appear at the Israel Defense Forces Recruiting Office for
      medical examination except for orthodox religious and Arabic adolescents.
      Cardiology specialists evaluated and classified nominees with suspected
      cardiovascular disorders. RESULTS: The most prevalent diagnoses were valvular
      heart disease (590/ 100,000), syncope (440/100,000), and mitral valve prolapse
      (340/100,000). The most prominent differences between female and male adolescents
      were noted in the prevalence of: congenital valvular heart disease, syncope,
      history of hypertension, supraventricular tachycardia with pre-excitation,
      myocarditis and pericarditis, and bradycardia and conduction disorders.
      CONCLUSIONS: The most prevalent cardiac disorders among 17-year-old Israelis were
      congenital valvular heart disease, syncope and mitral valve prolapse. Some
      significant differences were noted between the morbidity patterns among male and
      female adolescents. The higher prevalence of congenital valvular heart disease
      compared to non-valvular heart disease is surprising. The prevalence of
      hypertension among Israeli adolescents in the last 15 years remained stable.

PMID- 15942177
TI  - Do patients with right ventricular outflow tract ventricular arrhythmias have a
      normal right ventricular wall motion? A quantitative analysis compared to normal
      subjects.
AB  - BACKGROUND/AIM: Patients with ventricular ectopy from the right ventricular (RV)
      outflow tract (RVOT) are often referred for RV angiography to exclude disorders
      such as arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). This is usually
      based on a qualitative assessment of the wall motion. We present a method to
      quantify the wall motion and to apply this method to compare patients with RVOT
      ectopy to normal subjects. METHODS: RV angiograms were analyzed from 19 normal
      subjects and 11 subjects with RVOT ventricular arrhythmias (RVOT arrhythmia
      subjects) who had no other clinical or other evidence for ARVC/D. By a newly
      developed computer-based method, RV contours were first traced from multiple
      frames spanning the entire cardiac cycle. The fractional change in area between
      contours was then calculated as a serial function of time and location to
      determine both total contour area change and timing of contour movement. Contour
      area strain, defined as the differential change in area between nearby regions,
      was also computed. RESULTS: The contour area change was greatest in the tricuspid
      valve region and least in the RVOT and midanterior regions. The onset of
      contraction was earliest in the RVOT region and latest in the apical, inferior,
      inferoapical, and subtricuspid valve regions. The contour strain was largest in
      superior tricuspid valve and inferior wall and near zero within the lateral
      tricuspid valve region. There were significant pairwise differences in
      contraction area, timing, and strain in the various regions. There were no
      significant differences between normal subjects and RVOT arrhythmia subjects.
      CONCLUSIONS: The RV wall motion is nonuniform in contour area change, strain, and
      timing of motion. Patients with RVOT ventricular ectopy demonstrate wall motion
      parameters similar to those of normal subjects. This technique should be
      applicable in analyzing RV wall motion in patients suspected of having ARVC/D.

PMID- 15942178
TI  - Effect of beta-blocker therapy on myocardial perfusion defects in thallium-201
      scintigraphy in patients with dilated cardiomyopathy.
AB  - BACKGROUND: The beneficial effects of beta-blocker therapy in patients with heart
      failure have been confirmed. However, the effects of beta-blockers on myocardial
      perfusion defects are unclear. The aim of this study was to evaluate the effect
      of beta-blockers on myocardial perfusion defects estimated by thallium-201
      myocardial scintigraphy in patients with dilated cardiomyopathy (DCM) and to
      investigate the relationships between beta-blocker treatment and myocardial
      damage and cardiac function. METHODS: 201Tl and echocardiography were performed
      in 37 patients before and after 6 months of beta-blocker therapy. Extent score
      (ES) by 201Tl was used to quantitate myocardial perfusion defects before and
      after treatment. RESULTS: ES was significantly decreased by beta-blocker therapy.
      According to the change in ES, DCM patients were classified into three groups,
      patients who improved, patients showing no change and patients who deteriorated.
      In the improvement and no-change groups, beta-blocker therapy induced a reduction
      in left ventricular dimensions and an associated increase in ejection fraction.
      However, in the deterioration group, left ventricular dimensions and ejection
      fraction were unchanged. There was a significant relationship between the change
      in left ventricular dimension at end-diastole and the change in ES. CONCLUSIONS:
      beta-Blocker therapy could attenuate myocardial perfusion defects in some
      patients with DCM. The improvement in left ventricular function associated with
      beta-blocker therapy may be related to the attenuation in myocardial perfusion
      defects.

PMID- 15942179
TI  - Atrial septal aneurysm with multiple atrial septal defects: cribriform atrial
      septal aneurysm.

PMID- 15942180
TI  - Diabetic nephropathy, percutaneous coronary interventions, and blockade of the
      renin-angiotensin system.
AB  - Since recent studies demonstrated an impaired outcome after percutaneous coronary
      interventions (PCI) in patients with chronic renal failure but did not address
      the aetiology of renal failure, we now analysed the outcome of patients with
      diabetic nephropathy in 721 consecutive patients undergoing PCI. Diabetic
      nephropathy was present in 37 patients (5.1%), and diabetes alone in 126 patients
      (17.5%); 178 patients (24.7%) suffered from renal insufficiency of other causes;
      the other 380 patients (52.7%) were used as controls. Although angiographic
      success rates were similar in the subgroups (94-97%), 30-day and long-term
      mortality after 4 years was significantly higher in patients with diabetic
      nephropathy (8.1 and 27%, respectively) than in diabetics (1.6 and 8.7%,
      respectively), patients with renal insufficiency (3.9 and 16.8%, respectively),
      or controls (2.4 and 5.0%, respectively, each p<0.001, log-rank test). Treatment
      with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      was associated with a marked decrease in 2-year mortality in patients with
      diabetic nephropathy (19.4 vs. 33.3%, respectively, p=0.02, log-rank test).

PMID- 15942181
TI  - Migrating thrombus trapped in patent foramen ovale: resolution with
      anticoagulation treatment.

PMID- 15942182
TI  - Advanced interatrial block: a classic electrocardiogram.
AB  - Interatrial block (IAB; P wave>or=110 ms) indicates conduction delay between the
      right and left atria. IAB can present as partial or advanced and is denoted on
      the electrocardiogram (ECG) by bifid or biphasic P waves, respectively, the
      latter in inferior leads. The importance of IAB cannot be overemphasized due to
      high prevalence, especially at ages 60 and over, and due to grave associations
      with atrial flutter and fibrillation as well as congestive heart failure. Thus,
      we present a classic ECG of the much less common form of IAB, namely advanced
      IAB, as it serves as an excellent yardstick and teaching tool to help clinicians
      understand this medical entity thoroughly and to easily recognize this often
      missed type of block.

PMID- 15942183
TI  - Serial antiarrhythmic therapy: role of amiodarone in prevention of atrial
      fibrillation recurrence--a lesson from the HOT CAFE Polish Study.
AB  - Antiarrhythmic drug prophylaxis is known to improve long-term success of
      electrical cardioversion (CV) in persistent atrial fibrillation (AF). This
      prospective study evaluates the efficacy of sequential antiarrhythmic drug
      therapy in sinus rhythm (SR) maintenance after successful elective CV in patients
      with persistent nonvalvular AF. MATERIALS AND METHODS: One hundred and twenty
      eight patients (61+/-8 years old) with persistent AF underwent CV. Mean AF
      duration preceding CV was 268+/-99 days. Following SR restoration, patients were
      treated sequentially with either of the following antiarrhythmic drugs:
      propafenone, sotalol or disopyramide. Where arrhythmia recurred, patients
      received another CV and a new drug from the range defined above. Where such
      treatment failed, patients were loaded with 14.0- to 16.0-gram doses of
      amiodarone and a third CV was performed. If the first CV failed to restore SR,
      patients received a loading dose of amiodarone followed by another CV. When
      successful, amiodarone was administered on continuous basis. RESULTS: The first
      CV proved successful in 55.5% of patients. During 1-year of follow-up, 31
      patients (43.7%) presented with SR were treated with one antiarrhythmic agent
      (median does not exist). Application of the second drug proved to be effective in
      6 patients (15.0%; median 13 days). Amiodarone was administered as the third
      antiarrhythmic agent to patients who had AF recurrence on the first two
      antiarrhythmic agents (propafenone, sotalol or disopyramide). It proved to be
      effective in 18 patients (52.9%; median does not exist) remaining free from AF
      for a period of 1 year as of commencement of the sequential antiarrhythmic
      therapy. Fifty-seven patients, in whom the first CV was ineffective, received
      amiodarone. During the loading period, SR was restored in 7 patients (12.3%). The
      remaining 50 patients underwent repeated CV, with SR restored in 37 (74.0%) of
      them. Long-term amiodarone treatment maintained SR in 30 (68.2%) patients during
      the follow-up period. Amiodarone helped to maintain SR in a total of 56.5% of
      patients. CONCLUSIONS: Amiodarone seems to be the drug most effectively restoring
      and maintaining SR in patients with persistent AF resistant to CV and standard
      antiarrhythmic drug prophylaxis.

PMID- 15942184
TI  - Role of glucose side chains with serotype-specific polysaccharide in the
      cariogenicity of Streptococcus mutans.
AB  - Previously, we isolated and characterized a new Streptococcus mutans strain
      (serotype k) from human blood and oral cavity samples, and found that the
      serological properties of serotype k strains were similar to those of a gluA
      inactivated mutant strain of MT8148 (MT8148GD). MT8148GD showed significantly
      lower sucrose-dependent adhesion to glass surfaces, sucrose-independent adhesion
      to saliva-coated hydroxyapatite, dextran-binding activity, and cell-associated
      glucosyltransferase (GTF) activity than the parent strain. Further, Western blot
      analysis revealed reduced GTFB and GTFC expression in serotype k strains as
      compared to MT8148, though the caries-inducing activities of MT8148GD and a
      serotype k oral isolate in rats were similar to that of MT8148. We conclude that
      a glucose side-chain defect in the serotype-specific polysaccharide of S. mutans
      may be associated with its cariogenicity, though to a lesser extent than its
      other major surface proteins.

PMID- 15942185
TI  - Responder and nonresponder analysis for a caries prevention program.
AB  - To be able to generalize studies, it is important to know whether responders and
      nonresponders differ significantly. These data are usually not available. To
      assess whether responders and nonresponders differed significantly, 319 first and
      second graders in Greifswald, Germany took part in a compulsory dental school
      examination. Their parents completed a questionnaire on oral health topics and
      were asked to decide about their children's participation in a school-based
      caries prevention program plus anonymous scientific evaluation. The 91 children
      who were not allowed to participate (nonresponders) were older (mean 8.5 years)
      than the 228 responders (mean 8.1 years; p < 0.001), mostly because of a few
      older children having repeated a grade. In an age-adjusted analysis,
      nonresponders exhibited in 21 of 30 indices of higher caries and plaque values,
      less preventive measures and a lower rate of participation. The difference in
      caries in the permanent dentition and fluorosis reached statistical significance.
      This study suggests that nonresponders to caries prevention programs might comply
      less with preventive measures and exhibit poorer oral health than responders: a
      result which has to be taken into account in research and prevention programs in
      the community.

PMID- 15942187
TI  - Clinical study on the effect of professional cleaning of occlusal tooth surfaces
      on laser fluorescence measurements.
AB  - Manufacturer's advice is to professionally clean teeth before using a laser
      fluorescence (LF) device in order to avoid false-positive diagnoses. Professional
      cleaning is not included in routine dental check-ups in children in Finland
      because it is time-consuming. The aim of our present study was to evaluate the
      effect of professional cleaning of teeth on LF in children. A total of 642
      occlusal surfaces in permanent molars and premolars in 9- to 16-year-olds (n =
      46) were first examined visually. After that the first measurements with LF were
      made without cleaning the teeth. At the same appointment the second measurements
      were carried out after professional cleaning using a soft rubber cup and either
      polishing paste or plain water spray. The differences in LF of uncleaned and
      cleaned teeth were determined separately for teeth with a visual score of 0
      (sound) and > 0. In premolars cleaning had no significant effect on LF. In
      molars, the values increased when the teeth were cleaned, the difference of the
      measurements being statistically significant in molars with visual score > 0
      cleaned with plain water spray. For molars that were cleaned with paste, the
      differences were not statistically significant. Sealants did not modify the
      effect of cleaning. As a conclusion cleaning with a rotating instrument and water
      spray before LF measurements is recommended in teeth with visible plaque. Also in
      clean teeth, cleaning is advisable in cases where LF readings approach threshold
      level for operative intervention. The finding that uncleaned teeth gave lower
      values than cleaned teeth is opposite to what has been suggested.

PMID- 15942186
TI  - Effect of school-based fluoride varnish programmes on approximal caries in
      adolescents from different caries risk areas.
AB  - The aim was to evaluate, in a 3-year RCT study, school-based fluoride varnish
      programme on approximal caries incidence and approximal caries progression in 13-
      to 16-year-olds in high, medium and low caries risk areas on the Swedish west
      coast. Seven hundred and fifty-eight (89%) fulfilled the trial. Using a simple
      mobile unit, 2 dental nurses treated the adolescents with F varnish: (1) twice a
      year at 6-month intervals, (2) 3 times a year within 1 week, (3) 8 times per year
      during the semesters with 1-month intervals, and (4) no treatment (control).
      Radiographic caries recording was performed blindly by one of the authors.
      Concerning total approximal caries incidence, control groups in all areas
      developed more caries than F varnish groups, with the largest difference in the
      high risk area: 3.05 +/- 3.37 new approximal caries lesions (mean +/- SD)
      compared to 0.54 +/- 1.26 for group 3, 0.95 +/- 1.67 for group 1 and 1.40 +/-
      1.89 for group 2 (p < 0.001). More than 90% of the new approximal lesions in all
      the groups and in all areas consisted of new enamel lesions. Regarding
      progression of enamel lesions, there were only significant differences between
      groups 1-3 and group 4 in the high caries risk area. Prevented fraction for
      fluoride varnish treatment twice a year at 6-month intervals was 69% in high, 66%
      in medium and 20% in low risk areas. To conclude, school-based F varnish
      treatment every 6 months in 13- to 16-year-olds is excellent to prevent
      approximal caries in medium and high caries risk areas.

PMID- 15942188
TI  - Influence of professional cleaning and drying of occlusal surfaces on laser
      fluorescence in vivo.
AB  - Three dentists recorded laser fluorescence (LF) values on 117 teeth in 70
      patients, in the sequence: (1) moist, uncleaned; (2) dried, uncleaned; (3) moist,
      cleaned; (4) dried, cleaned. LF values varied significantly with surface status
      (p < 0.01). The optimal cutoffs were up to 5 units lower on uncleaned, moist
      surfaces compared to the other states. Drying uncleaned surfaces significantly
      increased LF readings for dentinal caries (p < 0.01). It was concluded that
      occlusal surfaces should be clean and dry, for precise longitudinal monitoring of
      caries with LF as well as for detailed visual inspection, which should precede LF
      measurements.

PMID- 15942189
TI  - Transforming growth factor-beta signaling during epithelial-mesenchymal
      transformation: implications for embryogenesis and tumor metastasis.
AB  - The molecular mechanisms of epithelial-mesenchymal transformation (EMT) have long
      been studied to gain a greater understanding of this distinct change in cellular
      morphology. Early studies of the developing embryo have designated the
      involvement of Wnt signaling in EMT, through an activated complex of the lymphoid
      enhancing factor-1 (LEF-1) transcription factor and the cell adhesion molecule
      beta-catenin. However, more recent studies have implicated a significant role of
      the transforming growth factor-beta (TGF-beta) in causing EMT in both development
      and pathology. The ability of TGF-beta isoforms to signal through a variety of
      molecules such as Smads, phosphatidylinositol 3-kinase (PI3K), and mitogen
      activated protein kinase (MAPK) creates an incredible complexity as to their role
      in this transition. Here we assess the biochemical signaling pathways of TGF-beta
      and their potential cross-interaction with traditional Wnt signaling molecules to
      bring about EMT during embryogenesis and tumor metastasis.

PMID- 15942190
TI  - Regulatory mechanisms for neural crest formation.
AB  - In early vertebrate development, the neural crest is specified in the embryonic
      ectoderm at the boundary of the neural plate and the nonneural ectoderm. After
      the induction, the neural crest cells undergo epithelial-mesenchymal transition,
      delaminating from the epithelium, and migrate extensively in the embryonic
      environment to give rise to a wide variety of tissues and cell types. In this
      review, we try to summarize the recent progress in understanding the molecular
      nature of the inductive signals and transcription factors involved in neural
      crest formation and following steps of the neural crest development. We also
      point out the underlying problems that need to be solved to understand the
      process further.

PMID- 15942191
TI  - Mesenchymal-to-epithelial transition during somitic segmentation: a novel
      approach to studying the roles of Rho family GTPases in morphogenesis.
AB  - During early development in vertebrates, cells change their shapes dramatically
      both from epithelial to mesenchymal and also from mesenchymal to epithelial,
      enabling the body to form complex tissues and organs. Using somitogenesis as a
      novel model, Rho family GTPases have recently been shown to play essential and
      differential roles in individual cell behaviors in actual developing embryos.
      Levels of Cdc42 activity provide a binary switch wherein high Cdc42 levels allow
      the cells to remain mesenchymal, while low Cdc42 levels produce
      epithelialization. Rac1 activity needs to be precisely controlled for proper
      epithelialization through the bHLH transcription factor Paraxis. Somitogenesis is
      expected to serve as an excellent model with which one can understand how the
      functions of developmental genes are resolved into the morphogenetic behavior of
      individual cells.

PMID- 15942192
TI  - Transforming growth factor-beta-induced epithelial-mesenchymal transition in the
      lens: a model for cataract formation.
AB  - The vertebrate lens has a distinct polarity and structure that are regulated by
      growth factors resident in the ocular media. Fibroblast growth factors, in
      concert with other growth factors, are key regulators of lens fiber cell
      differentiation. While members of the transforming growth factor (TGFbeta)
      superfamily have also been implicated to play a role in lens fiber
      differentiation, inappropriate TGFbeta signaling in the anterior lens epithelial
      cells results in an epithelial-mesenchymal transition (EMT) that bears
      morphological and molecular resemblance to forms of human cataract, including
      anterior subcapsular (ASC) and posterior capsule opacification (PCO; also known
      as secondary cataract or after-cataract), which occurs after cataract surgery.
      Numerous in vitro and in vivo studies indicate that this TGFbeta-induced EMT is
      part of a wound healing response in lens epithelial cells and is characterized by
      induced expression of numerous extracellular matrix proteins (laminin, collagens
      I, III, tenascin, fibronectin, proteoglycans), intermediate filaments (desmin,
      alpha-smooth muscle actin) and various integrins (alpha2, alpha5, alpha7B), as
      well as the loss of epithelial genes [Pax6, Cx43, CP49, alpha-crystallin, E
      cadherin, zonula occludens-1 protein (ZO-1)]. The signaling pathways involved in
      initiating the EMT seem to primarily involve the Smad-dependent pathway, whereby
      TGFbeta binding to specific high affinity cell surface receptors activates the
      receptor-Smad/Smad4 complex. Recent studies implicate other factors [such as
      fibroblast growth factor (FGFs), hepatocyte growth factor, integrins], present in
      the lens and ocular environment, in the pathogenesis of ASC and PCO. For example,
      FGF signaling can augment many of the effects of TGFbeta, and integrin signaling,
      possibly via ILK, appears to mediate some of the morphological features of EMT
      initiated by TGFbeta. Increasing attention is now being directed at the network
      of signaling pathways that effect the EMT in lens epithelial cells, with the aim
      of identifying potential therapeutic targets to inhibit cataract, particularly
      PCO, which remains a significant clinical problem in ophthalmology.

PMID- 15942193
TI  - Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition,
      mesenchymal-epithelial transition, stem cells and beta-catenin.
AB  - Invasion by colorectal carcinomas is characterized by an epithelial-mesenchymal
      transition (EMT)-like dedifferentiation of the tumor cells. However, a
      redifferentiation towards an epithelial phenotype, resembling a mesenchymal
      epithelial transition, is detectable in metastases. This indicates that malignant
      progression is based on dynamic processes, which cannot be explained solely by
      irreversible genetic alterations, but must be additionally regulated by the tumor
      environment. The main oncoprotein in colorectal cancer is the Wnt pathway
      effector beta-catenin, which is overexpressed due to mutations in the APC tumor
      suppressor in most cases. EMT of the tumor cells is associated with a nuclear
      accumulation of the transcriptional activator beta-catenin, which is reversed in
      metastases. Nuclear beta-catenin is involved in two fundamental processes in
      embryonic development: EMT and stem cell formation. Accumulating data demonstrate
      that aberrant nuclear expression of beta-catenin can also confer these two
      abilities to tumor cells, thereby driving malignant tumor progression.

PMID- 15942194
TI  - Hyaluronan: a critical component of epithelial-mesenchymal and epithelial
      carcinoma transitions.
AB  - Hyaluronan plays a central role in the transition of epithelia to mesenchyme in
      the embryo and in the acquisition of transformed properties in carcinoma cells.
      In some cases, hyaluronan is both essential and sufficient for induction of
      epithelial-mesenchymal transitions (EMTs). Underlying its role are the effects of
      hyaluronan on receptor kinase activities, cell survival pathways, and multidrug
      transporters. A more complete understanding of the mechanisms whereby hyaluronan
      exerts its influences on cell behavior will enhance our understanding of normal
      and pathological EMTs and may lead to improved therapies for cancer patients.

PMID- 15942195
TI  - The SRC-induced mesenchymal state in late-stage colon cancer cells.
AB  - One major function of elevated Src kinase in epithelial cancer cells is to drive
      adhesion changes that are associated with the mesenchymal transition and
      metastasis. Here we review recent work that describes Src-induced shape changes,
      and the mechanisms involved, in cells derived from a model of colon cancer
      metastasis. Src activity in these cells is associated with formation and dynamic
      regulation of integrin adhesions and disorganization of E-cadherin-dependent cell
      cell contacts. Furthermore, Src-induced deregulation of E-cadherin requires
      integrin signalling, demonstrating a complex interdependence between integrin-
      and cadherin-associated adhesion changes induced by Src. The integrin-induced
      signals that co-operate with Src to cause deregulation of cadherin-dependent cell
      cell contacts include activation of the MEK/ERK and MLCK/myosin activities.
      Inhibition of this pathway suppresses integrin complexes formed on fibronectin,
      while promoting E-cadherin redistribution to sites of cell-cell contacts. Also,
      in embryonic fibroblasts that express N-cadherin (which is normally diffusely
      cytoplasmic as these cells maintain a fibroblastic morphology) suppressing
      integrin signalling and inhibiting the MEK/ERK/MLCK/myosin pathway relocalizes N
      cadherin to cell-cell contacts. Our recent data therefore imply an important, and
      perhaps general, role for spatially controlled contractility in suppressing
      normal cadherin localization and inducing a mesenchymal-like phenotype.

PMID- 15942196
TI  - A perspective on regulation of cell-cell adhesion and epithelial-mesenchymal
      transition: known and novel.
AB  - A number of recent reviews in the field have described many of the known growth
      factors and signalling pathways that may be involved in regulating epithelial
      mesenchymal transitions. This perspective will focus on some aspects of
      posttranslational regulation of cell-cell adhesion that are less well understood
      and their potential role in initiating epithelial-mesenchymal transitions. In
      addition, a potential novel intermediate in the signalling pathway of epithelial
      mesenchymal transition will also be described.

PMID- 15942197
TI  - Neuropsychological correlates of MRI measures in the continuum of cognitive
      decline at old age.
AB  - OBJECTIVE: To investigate the independent associations between medial temporal
      lobe atrophy and white matter hyperintensities (WMH) and cognitive functions in
      the elderly. METHODS: Cognitive functions of 41 Alzheimer's disease patients, 20
      patients with mild cognitive impairment and 28 elderly subjects without memory
      complaints were assessed using a neuropsychological test battery. Quantitative
      MRI measures of medial temporal lobe volume and WMH were obtained. Multiple
      regression analyses were performed to assess the independent contribution of MRI
      measures to impairment in several cognitive functions. RESULTS: Scores on the
      Wechsler Memory Scale and Trails B depended selectively on medial temporal lobe
      volume, whereas WMH selectively contributed to performance on Trails A. Medial
      temporal lobe volume and WMH both contributed to scores on the Cambridge
      Cognitive Examination and the Boston naming task. CONCLUSIONS: MRI measures
      suggestive of Alzheimer-type pathology and microvascular pathology independently
      contribute to cognitive decline at old age. Memory impairment as measured using
      the Wechsler Memory Scale and performance on Trails B primarily depended on
      medial temporal lobe atrophy. Psychomotor slowness, as measured using Trails A,
      mainly depended on WMH. These results suggest that vascular pathology and
      Alzheimer-type pathology each have specific cognitive correlates.

PMID- 15942198
TI  - Pathophysiology of acute pancreatitis. If you believe in mice--it's time for
      conditional gene targeting!

PMID- 15942199
TI  - Pathophysiology of acute experimental pancreatitis: lessons from genetically
      engineered animal models and new molecular approaches.
AB  - The incidence of acute pancreatitis is growing and worldwide population-based
      studies report a doubling or tripling since the 1970s. 25% of acute pancreatitis
      are severe and associated with histological changes of necrotizing pancreatitis.
      There is still no specific medical treatment for acute pancreatitis. The average
      mortality resides around 10%. In order to develop new specific medical treatment
      strategies for acute pancreatitis, a better understanding of the pathophysiology
      during the onset of acute pancreatitis is necessary. Since it is difficult to
      study the early acinar events in human pancreatitis, several animal models of
      acute pancreatitis have been developed. By this, it is hoped that clues into
      human pathophysiology become possible. In the last decade, while employing
      molecular biology techniques, a major progress has been made. The genome of the
      mouse was recently sequenced. Various strategies are possible to prove a causal
      effect of a single gene or protein, using either gain-of-function (i.e.,
      overexpression of the protein of interest) or loss-of-function studies (i.e.,
      genetic deletion of the gene of interest). The availability of transgenic mouse
      models and gene deletion studies has clearly increased our knowledge about the
      pathophysiology of acute pancreatitis and enables us to study and confirm in
      vitro findings in animal models. In addition, transgenic models with specific
      genetic deletion or overexpression of genes help in understanding the role of one
      specific protein in a cascade of inflammatory processes such as pancreatitis
      where different proteins interact and co-react. This review summarizes the recent
      progress in this field.

PMID- 15942200
TI  - Reflux questionnaire (ReQuest).

PMID- 15942202
TI  - Gastric eosinophilic granuloma in China: case series.
AB  - AIM: Eosinophilic granulomas are benign localized lesions in the stomach that are
      distinct from eosinophilic gastritis. The aim of this study was to identify the
      potential etiological factors and clinical features of gastric eosinophilic
      granulomas (GEG). METHODS: Clinical manifestations, histopathological features,
      diagnosis and treatments of 48 hospitalized cases of GEG were analyzed
      retrospectively. A modified Giemsa staining was employed to detect Helicobacter
      pylori in 23 of these 48 patients. RESULTS: There was a significant gender
      difference among patients with GEG with male patients significantly more affected
      than female patients. The final diagnosis was made after operating the patients
      (the misdiagnosis level was rather high before resection). Lymphoid follicles
      were found in 68.6% of the tissues surrounding the lesion. H. pylori infection
      was detected in 69.6% of patients. In 11 patients eosinophilia in the peripheral
      blood was observed. CONCLUSION: The results suggest that H. pylori infection,
      estrogen status and local allergic reactions may be associated with the
      development of GEG.

PMID- 15942203
TI  - Effect of acute hyperglycemia on intestinal gas transit and tolerance in
      nondiabetic humans.
AB  - BACKGROUND: Acute hyperglycemia usually inhibits gastrointestinal motility and
      hyperinsulinemia may contribute to specific inhibitory effects. However, the
      influences on postprandial intestinal gas dynamics have not been investigated.
      AIMS: To compare effects of euglycemic hyperinsulinemia and acute fasting
      hyperglycemia on intestinal gas dynamics in nondiabetics. METHODS: On 3 separate
      days, 10 healthy volunteers were evaluated in randomized order with duodenal
      glucose, intravenous glucose or saline infusion. Rectal gas evacuation was
      continuously measured; perception and abdominal girth changes were separately
      evaluated. After 60 min equilibration, proximal jejunal gas infusion (12 ml/min)
      was started for 150 min. RESULTS: Acute hyperglycemia failed to cause significant
      intestinal gas retention (72 +/- 64 ml and 53 +/- 29 ml final gas retention vs.
      saline); in contrast, gas clearance was expedited, with a maximal effect between
      30 and 105 min (p < 0.001 vs. control). Euglycemic hyperinsulinemia did not
      significantly influence intestinal gas clearance and no relevant changes of
      abdominal girth or abdominal and rectal perception were seen, as compared to
      control (p > 0.05 for all parameters). CONCLUSION: Accelerated intestinal gas
      clearance under hyperglycemia is one physiologic factor to avoid postprandial
      intestinal gas accumulation. Specific underlying mechanisms, which need further
      investigation, may be disturbed in symptomatic patients.

PMID- 15942204
TI  - Utility of electrogastrography in differentiating Parkinson's disease with or
      without gastrointestinal symptoms: a prospective controlled study.
AB  - BACKGROUND/AIMS: Parkinson's disease (PD) may be associated with various
      gastrointestinal symptoms. This study was designed to assess the gastric
      myoelectrical functioning in patients with PD and in healthy controls by using
      electrogastrography (EGG) with the water load test and to determine the clinical
      utility of EGG in differentiating PD patients with or without upper
      gastrointestinal symptoms. METHODS: Twenty patients (13 men, mean age 63 years)
      with PD and 11 healthy controls (5 men, mean age 55 years) were studied. The PD
      patients were stratified into two subgroups: 9 were assessed as PD without upper
      gastrointestinal symptoms (group A) and 11 as PD with upper gastrointestinal
      symptoms (group B). The gastric myoelectrical activity was assessed using
      cutaneous electrodes to record EGG before and after the subjects ingested water
      until full. RESULTS: The PD patients drank significantly less water until full as
      compared with the controls (303 +/- 45 vs. 627 +/- 67 ml, p < 0.05). At baseline,
      the PD patients had a significantly higher 1.0- to 2.5-cpm activity as compared
      with the controls (44 +/- 3 vs. 33 +/- 3%, p < 0.05). These differences persisted
      after ingestion of the water load. The PD patients had a significantly lower 2.5-
      to 3.75-cpm activity late after ingestion of the water load as compared with the
      controls (33 +/- 4 vs. 49 +/- 5%, p < 0.05). No statistically significant
      differences were found in any EGG variables or the water load between the two
      groups of PD patients. CONCLUSIONS: This study has shown that the gastric
      myoelectrical activity is impaired in both groups of PD patients. EGG appears to
      have a limited, if any, clinical utility in the differentiation of PD patients
      with or without upper gastrointestinal symptoms.

PMID- 15942205
TI  - Pathophysiological roles of ectopic tachygastria induced with antral electrical
      stimulation.
AB  - AIM: To investigate the pathophysiological roles of tachygastria using antral
      electrical stimulation (AES). METHODS: The study was performed on 13 healthy
      female hound-type dogs chronically implanted with three pairs of serosal
      electrodes and a gastric cannula (n = 7). In the first experiment (n = 7), the
      antral motility was measured for three 30-min periods right after a solid meal.
      AES was performed during the second 30-min period at a tachygastric frequency. In
      the second experiment (n = 6), gastric slow waves and animal behavior were
      monitored in the fasting state at baseline and with various parameters of AES.
      RESULTS: (1) AES at tachygastric frequencies (7-14 cpm) significantly reduced the
      percentage of normal 4- to 6-cpm slow waves and induced tachygastria; (2) AES
      significantly and substantially inhibited the antral motility in the fed state;
      (3) AES in the fasting state energy dependently induced symptoms, and the symptom
      score was linearly correlated with the stimulation frequency, and (4) there was a
      significant negative correlation between percentage of tachygastria and index of
      antral motility. CONCLUSIONS: AES induces tachygastria and inhibits the antral
      motility. Tachygastria is correlated with antral motility.

PMID- 15942206
TI  - Cronkhite-Canada syndrome.

PMID- 15942207
TI  - A case of Cronkhite-Canada syndrome with taste disturbance as a leading
      complaint.
AB  - Cronkhite-Canada syndrome was first described in 1955. The clinical features of
      this rare syndrome of unknown etiology include nonhereditary gastrointestinal
      polyposis together with diarrhea, nail dystrophy, alopecia, and hyperpigmentation
      of the skin. This syndrome has been divided into five clinical types based on
      initial symptoms. We describe a case of Cronkhite-Canada syndrome presenting with
      taste disturbance as the major symptom, present a comprehensive review of the
      literature concerning this rare syndrome, and suggest therapeutic treatment
      options.

PMID- 15942208
TI  - Erythema toxicum neonatorum: still a problem in 2005?

PMID- 15942209
TI  - Are viral infections responsible for the development of drug-induced
      hypersensitivity syndrome as well as graft-versus-host diseases?

PMID- 15942210
TI  - Two decades experience of the Psoriasis Disability Index.
AB  - The Psoriasis Disability Index (PDI) was formed 20 years ago. Since its
      introduction it has been used widely as a tool for assessment of quality of life
      in psoriasis. This paper reviews its use in 23 peer-reviewed articles and over 35
      published abstracts, and describes its use in conjunction with other general and
      psoriasis-specific quality of life assessments, and with a range of physical and
      psychological measures. The PDI is effective in demonstrating the effects of
      interventions, both of treatments and in health service research. The PDI has
      been translated into at least 16 languages and has been used in published
      research in 20 countries.

PMID- 15942211
TI  - Epidemiologic study of the predisposing factors in erythema toxicum neonatorum.
AB  - BACKGROUND: Erythema toxicum neonatorum (ETN) is a very common disease, but its
      predisposing factors are still unknown. OBJECTIVE: To determine the predisposing
      factors of ETN. METHODS: Seven hundred and eighty-three neonates born in the same
      hospital during the same period were investigated, and the factors predisposing
      to ETN were evaluated in a case-control study. RESULTS: (1) The incidence of ETN
      is about 43.68%, and it is significantly higher in males than in females (p <
      0.001). (2) Term birth (p < 0.05), first-pregnancy birth (p < 0.001), the birth
      season (summer and autumn, p < 0.005), being fed with milk powder substitute or a
      mixed diet (p < 0.001) and vaginal delivery (p < 0.001) are the predisposing
      factors of ETN. (3) The severity of ETN in neonates born by vaginal delivery is
      significantly correlated with the total length of labor (p < 0.001). CONCLUSION:
      Our findings suggest that environmental factors play an important role in the
      onset of ETN.

PMID- 15942212
TI  - Novel application of layered expression scanning for proteomic profiling of
      plucked hair follicles.
AB  - BACKGROUND: There is a need for a technology that can quantitatively assay
      multiple proteins from a single hair follicle while preserving the morphology of
      the follicle. For proteomic profiling, the technology should be less labor
      intensive, with a higher throughput, more quantitative and more reproducible than
      immunohistochemistry. OBJECTIVE: To test the ability of a novel method, layered
      expression scanning of hair (LES-hair) to detect the levels and localization of
      proteins in plucked hair follicles. METHODS: LES-hair was used to assay proteins
      in the plucked hair follicle. RESULTS: LES-hair detected differential expression
      of proteins within discrete regions of the plucked hair follicle. These proteins
      included cleaved caspase 3, Ki-67 and the phosphorylated forms of c-Kit,
      epidermal growth factor receptor and vascular endothelial growth factor receptor.
      CONCLUSION: LES-hair provides a research tool for studying the basic biology of
      plucked hair follicles and has potential clinical applications such as monitoring
      treatment of alopecia or using plucked hair follicles as a surrogate tissue to
      monitor pharmacodynamic effects of targeted cancer therapies.

PMID- 15942213
TI  - Quality of life and stigmatization profile in a cohort of vitiligo patients and
      effect of the use of camouflage.
AB  - BACKGROUND: Few studies have paid attention to the effects of treatment
      interventions on the psychosocial consequences of vitiligo. OBJECTIVES: To
      quantify and analyse the psychosocial benefit of the use of camouflage in
      vitiligo patients. PATIENTS AND METHODS: 78 vitiligo patients completed the
      Dermatology Life Quality Index (DLQI) and an adapted stigmatization
      questionnaire, and 62 of them completed the DLQI after at least a 1-month use of
      camouflage. RESULTS: The initial mean overall DLQI score (n = 78) is 6.9 (SD
      5.6). The mean global stigmatization score is 38%. Disease extent and disease
      severity are strong predictors of the DLQI (p < 0.0001). Vitiligo on the
      face/head/neck substantially affects the DLQI, independently of degree of
      involvement. The mean DLQI score before and after use of camouflage (n = 62) is
      7.3 (SD 5.6) and 5.9 (SD 5.2; p = 0.006). Mainly the high-scoring items 'feelings
      of embarrassment and self consciousness' and 'choice of clothing' improve.
      Predictors of improvement are higher DLQI scores (p = 0.0005) and higher total
      severity scores (p = 0.03). CONCLUSIONS: Camouflage can be recommended,
      particularly in patients with higher DLQI scores or self-assessed disease
      severity. Patients with minor involvement of the face benefit from camouflage.

PMID- 15942214
TI  - Psychophysiological reactivity under mental stress in atopic dermatitis.
AB  - BACKGROUND: An association of mental stress with atopic dermatitis is widely
      accepted. However, no long-term evaluation of psychophysiological reactivity over
      the course of disease has yet been performed. OBJECTIVE: We examined whether
      atopic dermatitis patients have an increased psychophysiological reactivity
      compared to healthy controls and in between acute and disease-free phases, and
      whether they differ in psychological state and trait variables. METHODS: Fifteen
      patients with atopic dermatitis underwent a stress test during acute exacerbation
      and after symptom improvement and were compared to matched controls. RESULTS:
      Psychophysiological responses to stress were not stronger in the patient group
      than in the controls. Nevertheless, the patients had a higher heart rate and
      lower vagal activity throughout the resting and stress phases at both examination
      times. The patients showed significantly higher anxiety, depression and emotional
      excitability, and self-ratings of inactivity clearly distinguished acute phases
      from remission. CONCLUSION: There is an increased vegetative excitability level
      in patients with atopic dermatitis, which cannot be attributed solely to
      increased disease activity.

PMID- 15942215
TI  - A two-compound product containing calcipotriol and betamethasone dipropionate
      provides rapid, effective treatment of psoriasis vulgaris regardless of baseline
      disease severity.
AB  - BACKGROUND: A two-compound product containing calcipotriol and betamethasone
      dipropionate (Daivobet/Dovobet) has been evaluated in a large clinical trial
      programme, providing a wealth of data on the treatment of psoriasis vulgaris.
      OBJECTIVE: To determine the effectiveness of the two-compound product in patients
      with mild, moderate and severe psoriasis vulgaris. METHODS: Data from over 1,534
      patients with psoriasis vulgaris who received the two-compound product once daily
      for at least 4 weeks in four randomised, double-blind studies were pooled. A meta
      analysis of the pooled data is presented. Severity of psoriasis at baseline was
      determined by investigator assessment and Psoriasis Area and Severity Index
      (PASI) score. RESULTS: For patients with severe disease defined by PASI score
      (PASI baseline > or = 17), the mean reduction in PASI after up to 4 weeks of
      treatment was 71.6% compared with 68.9 and 67.2% for those with moderate (PASI
      baseline 5.1-16.0) and mild disease (PASI baseline < or = 5). Corresponding
      reductions for investigator-assessed severity were 72.6, 69.1 and 68.7%,
      respectively. CONCLUSION: Although the meta-analysis of the data from these four
      studies was performed post hoc, we may conclude that the two-compound product
      provided highly effective treatment of psoriasis, regardless of the category of
      baseline disease severity.

PMID- 15942216
TI  - Critical appraisal of reports on the treatment of perioral dermatitis.
AB  - BACKGROUND: Presently, problems exist with the rationale of oral therapy and the
      nature and indication of topical and accompanying treatment of perioral
      dermatitis. OBJECTIVE: Providing the basis to overcome these problems by a
      quality evaluation of treatment reports and assessment of the consistency of
      treatment experience. METHODS: Sources were Medline (1964-2004), Embase (1966
      2004), the Cochrane Central (1971-2004) and 526 references of 3 textbooks, 2
      recent reviews and 30 papers on perioral dermatitis. Thirty English and German
      articles were selected. These studies were evaluated according to principles of
      evidence-based medicine and related criteria. Evaluation of 28 papers was carried
      out by the authors and of our own 2 papers by 2 other reviewers. Consistency of
      results was qualitatively assessed by the authors. RESULTS: There were only 2
      therapeutic trials of medium-range quality. The other studies were of low
      quality. Consistency was noted concerning treatment with oral tetracycline (with
      1 exception), discontinuation of topical corticosteroids and cosmetics and, to a
      lesser extent, regarding no therapy. There was inconsistency in respect to
      topical therapy. CONCLUSION: The presented data help to interpret and conduct
      studies on the treatment of perioral dermatitis.

PMID- 15942217
TI  - Netherton syndrome with extensive skin peeling and failure to thrive due to a
      homozygous frameshift mutation in SPINK5.
AB  - BACKGROUND: Netherton syndrome (NTS) is a rare autosomal recessive multisystem
      disorder characterized by congenital erythroderma and ichthyosis, hair shaft
      abnormalities and immune dysregulation. The disorder is caused by deleterious
      mutations in the SPINK5 gene, encoding the serine protease inhibitor LEKTI.
      OBJECTIVE: Our objective was to investigate if the erythrodermic variant of
      peeling skin syndrome is also caused by SPINK5 mutations and to study the
      consequences of the disease on infantile brain development. METHODS: In an infant
      with extensive erythroderma, peeling skin and failure to thrive, we analyzed the
      SPINK5 gene for pathogenic mutations by direct DNA sequencing and performed
      repeated brain MRI studies with diffusion-weighted imaging. RESULTS: We
      identified a homozygous 4-base-pair insertion in exon 5 of SPINK5, which
      introduces a premature termination codon and appears to be a common mutation
      among West Indies islanders. MRI analyses revealed a persistent diffuse volume
      loss. CONCLUSION: Our results confirm that early truncation mutations of the
      coding sequence of SPINK5 produce a severe phenotype and that generalized peeling
      skin is one of the manifestations of NTS. We further demonstrate for the first
      time that NTS may be associated with MRI abnormalities indicative of a permanent
      tissue injury of the brain.

PMID- 15942218
TI  - Extramammary Paget's disease not only mimicking but also accompanying condyloma
      acuminatum. A case report.
AB  - Although its significance remains unknown, it has recently been reported that
      epidermal papillomatous hyperplasia could be frequently found in extramammary
      Paget's disease (EMPD). The simultaneous occurrence of EMPD and various human
      papillomavirus (HPV)-associated neoplasms has also been reported. We report a
      case of a perianal EMPD with multiple verrucous papules on its surface.
      Histologically, the verrucous papules consisted of two distinct histological
      patterns; one showed numerous Paget's cells within the hyperplastic epidermis
      with papillomatosis, and the other showed the features compatible with condyloma
      acuminatum (CA). HPV-6 DNA was demonstrated in koilocytic keratinocytes of the CA
      by in situ hybridization. No positive signal was obtained for targeted HPV type
      6/11/16/18/31/33 DNA in either the verrucous or plaque EMPD. Since the verrucous
      papules were localized on the plaque of EMPD, our case suggests that some
      undetermined EMPD-related factors may contribute to the development of epithelial
      hyperplasia, including HPV-associated neoplasms.

PMID- 15942219
TI  - Three cases of transition from pemphigus vulgaris to pemphigus foliaceus
      confirmed by desmoglein ELISA.
AB  - We report 3 cases of pemphigus vulgaris (PV) confirmed by histology and direct
      and indirect immunofluorescence that showed transition to pemphigus foliaceus
      (PF) 2-4 years from the time of disease onset. Desmoglein (Dsg) ELISA testing of
      the sera from these 3 patients in the later stages of their disease showed the
      presence of anti-Dsg1 antibodies and the absence of anti-Dsg3 antibodies. These
      patients were on prednisolone and immunosuppressives at the time the sera were
      tested, and it is unclear if the transition from PV to PF is a permanent one or
      whether it is due to preferential suppression of Dsg3 antibodies below a certain
      threshold. Previously reported cases of transition from PV to PF and PF to PV are
      summarized.

PMID- 15942220
TI  - A patient with subclinical oculocutaneous albinism type 2 diagnosed on getting
      severely sunburned.
AB  - P-gene-related oculocutaneous albinism (OCA2) is an autosomal recessive disorder.
      The phenotype is typically somewhat less severe than that of the tyrosinase
      negative type (OCA1A). One of the mutations in the P gene, A481T, is associated
      with a mild phenotype, occasionally with no distinctive skin manifestations,
      which is called subclinical OCA. We present a Japanese patient having the A481T
      mutant allele in the P gene with subclinical oculocutaneous albinism diagnosed on
      getting severely sunburned. The A481T mutant allele is relatively common in the
      Caucasian population as well as in Japan, indicating that a number of subclinical
      patients of OCA2 might exist not only in Japan, but also all over the world.

PMID- 15942221
TI  - Ichthyosiform mycosis fungoides: report of a case associated with IgA
      nephropathy.
AB  - We report a case of ichthyosiform mycosis fungoides (MF) associated with IgA
      nephropathy. Histological examination showed a dense atypical lymphocytic
      infiltrate admixed with epithelioid cells and giant cells in the dermis
      associated with the features of epidermotropism and folliculotropism. Reported
      cases of ichthyosiform MF are reviewed and histopathological characters of
      ichthyosiform MF are summarized. We suggest a histiocyte/dendritic-cell-rich
      infiltrate, or granulomatous features of infiltrate may be another characteristic
      of ichthyosiform MF. This case was associated with IgA nephropathy, which is
      uncommon. Such a presentation has never been reported in the literature.

PMID- 15942222
TI  - Sclerodermic linear lupus panniculitis: report of two cases.
AB  - Lupus erythematosus panniculitis is a rare disease characterized by deep
      subcutaneous nodules, most commonly localized on the upper limbs and face. Unique
      clinical presentations, such as linear configuration or 'overlap' forms between
      lupus erythematosus panniculitis and localized scleroderma have been reported. We
      present here the clinical characteristics, course and laboratory findings of 2
      patients having linear lupus erythematosus panniculitis with localized
      scleroderma-like changes. The 2 patients (of the 14 patients with lupus
      erythematosus panniculitis seen by us since 1990) were females with a young age
      at the onset of disease (median, 25 years). In 1 case, evolution into systemic
      lupus erythematosus with severe renal involvement occurred whereas the other
      patient, who had a spontaneous abortion and exhibited anticardiolipin antibodies,
      should be followed and screened for the emergence of antiphospholipid syndrome.
      Thus, the clinical behavior of this variant seems to be more aggressive, as
      compared with the usual course of lupus erythematosus panniculitis, which is
      considered to be a benign disease, although some reports have suggested that its
      prognosis is not always favorable. The linear distribution could be the clinical
      hallmark of such a unique, 'sclerodermic' subset of lupus erythematosus
      panniculitis.

PMID- 15942223
TI  - Pseudocyst of the scalp.
AB  - We describe 4 cases of pseudocyst of the scalp, which still is only being
      described in the Japanese literature. The tumor is characterized as follows:
      localized between the top and the forehead area of the scalp, it first appears as
      a solitary reddish, painful small nodule or papule; it then gradually increases
      in size, protruding into a dome-shaped mass, and becomes associated with alopecia
      limited to the lesion area. This report describes typical cases of pseudocyst of
      the scalp, reviews the reported Japanese cases and introduces this tumor to
      western dermatology.

PMID- 15942224
TI  - Cutaneous manifestations as presenting sign of autoimmune lymphoproliferative
      syndrome in childhood.
AB  - Autoimmune lymphoproliferative syndrome is a disorder due to a defect of
      lymphocyte apoptosis, whose clinical manifestations consist of hyperplasia of
      lymphoid tissues and autoimmune diseases. We report on a 26-month-old child who
      presented with frequent eruptions of weals and angioedema without any apparent
      triggering factor, who subsequently developed an erythematopapular rash with a
      histological pattern of a lymphoplasmacellular infiltrate. Familial anamnesis
      revealed a history of lymphoadenomegaly and massive spleen and liver enlargement
      in her sister. Functional and molecular analysis led to a diagnosis of type 1a
      autoimmune lymphoproliferative syndrome. Immunophenotyping of the cutaneous
      lesion revealed the presence of an inflammatory infiltrate with a considerably
      high number of Langerhans cells. Cutaneous features such as urticaria, angioedema
      and vasculitis in children with a personal and familial history of hyperplasia of
      lymphoid tissues may be a presenting sign of a systemic disease, such as
      autoimmune lymphoproliferative syndrome.

PMID- 15942225
TI  - Atypical poorly differentiated cutaneous T-cell lymphoma with an angiocentric
      growth pattern presenting histologically as vasculitis.
AB  - We report the case of a 41-year-old patient with an aggressive cutaneous T-cell
      lymphoma (CTCL) initially presenting on histology as lymphocytic vasculitis. On
      repeated histological examination and by molecular biology work-up, the diagnosis
      of an unclassifiable CTCL could eventually be established. This atypical poorly
      differentiated lymphoma was of a CD4+ CD8- CD56- phenotype and followed an
      unfavourable course. The patient died despite chemo- and immunotherapy 7 months
      after the first consideration of lymphoma as diagnosis.

PMID- 15942226
TI  - The spontaneous regression of tufted angioma. A case of regression after two
      recurrences and a review of 27 cases reported in the literature.
AB  - BACKGROUND: Tufted angioma, a peculiar angioma that is characterized by tufts of
      capillary-sized vessels scattered 'cannonball fashion' within the dermis, is
      known, on occasion, to regress spontaneously. However, the appropriate waiting
      period for spontaneous regression has remained unclear. OBJECTIVE: To know the
      appropriate waiting period for spontaneous regression of tufted angioma. METHODS:
      We report here a case of tufted angioma that regressed spontaneously after the
      lesions had recurred twice. We also review previously reported cases of tufted
      angioma with spontaneous regression, including cases in the Japanese and non
      Japanese literature. RESULTS: In 18 (86%) of the 21 cases, the waiting period was
      more than 6 months and in 20 cases (95%) it was less than 2 years. CONCLUSION:
      The appropriate wait for spontaneous regression might be between 6 months and 2
      years.

PMID- 15942227
TI  - Drug-induced hypersensitivity syndrome associated with transient
      hypogammaglobulinaemia and increase in serum IgE level.
AB  - Drug-induced hypersensitivity syndrome (DIHS) is a rare but severe disease with
      multiorgan failure. Recently, the association of the human herpesvirus (HHV)
      family, particularly of HHV-6, with DIHS has been reported. We report a 43-year
      old female diagnosed as having DIHS based on the clinical course and laboratory
      examinations. The HHV-6 reactivation was demonstrated by significantly increased
      levels of the specific antibody in her paired sera and by polymerase chain
      reaction of HHV-6 DNA. Notably, transient hypogammaglobulinaemia was detected in
      the early stage of the disease, which was associated with the disease activity.
      By contrast, the serum IgE level and eosinophils were increased 2 or 3 weeks
      later. In addition, serum levels of interferon gamma, interleukin (IL)-4 and
      soluble IL-2 receptor, which were increased in the early phase of the disease,
      decreased gradually after the corticosteroid therapy.

PMID- 15942228
TI  - Pustular neutrophilic dermatoses and rapidly growing mycobacterium infection with
      bilateral cervical lymphadenopathy.

PMID- 15942229
TI  - Multiple linear erythema dyschromicum perstans (ashy dermatosis) in the lines of
      Blaschko.

PMID- 15942230
TI  - Hidroacanthoma simplex with inflammatory dermatosis-like lichenified plaque-type
      appearance.

PMID- 15942231
TI  - Superficial mucoceles of the soft palate.

PMID- 15942232
TI  - Hidroacanthoma simplex: a case report and analysis of 70 Japanese cases.

PMID- 15942233
TI  - Pruritus and leucocytoclastic vasculitis due to azathioprine.

PMID- 15942234
TI  - Superficial pyodermas: advances, recommendations and needs.

PMID- 15942235
TI  - Cloxacillin versus pristinamycin for superficial pyodermas: a randomized, open
      label, non-inferiority study.
AB  - BACKGROUND: Superficial pyodermas may require systemic antibiotics. In a previous
      open-label trial, oxacillin and pristinamycin achieved similar cure rates, but
      its design was not truly that of a non-inferiority study. OBJECTIVES: To assess
      the efficacy and safety of oral cloxacillin versus pristinamycin (both 2 g/day)
      to treat superficial pyodermas. METHODS: Multicentre, parallel-group, open-label,
      randomized non-inferiority trial. RESULTS: French general practitioners in
      private practice included 334 out-patients (mean age: 42 years). At the follow-up
      (day 14), the cure rates (primary efficacy end point) for the intent-to-treat
      populations were 80.7% (138/171) for cloxacillin and 82.8% (135/163) for
      pristinamycin. The observed difference between cure rates was -2.1%, with the
      lower limit of the two-sided 95% confidence interval higher than the non
      inferiority threshold of -15%. The per-protocol analysis yielded similar results.
      Therapy was discontinued for 10 patients (cloxacillin: 1, pristinamycin: 9; p =
      0.01). CONCLUSION: Cloxacillin could be an alternative to pristinamycin in out
      patients with superficial pyodermas.

PMID- 15942236
TI  - How to treat adenocarcinomas of the distal esophagus and the gastro-esophageal
      junction.

PMID- 15942237
TI  - Individualised surgical treatment of patients with an adenocarcinoma of the
      distal oesophagus or gastro-oesophageal junction.
AB  - In this review we discuss the different strategies to improve surgical outcomes
      after potentially curative resection for oesophageal adenocarcinoma. For tumours
      of the distal oesophagus, there is a 17% survival benefit after transthoracic
      resection with two-field lymph node dissection when compared with transhiatal
      resection. This survival benefit is absent for tumours of the gastro-oesophageal
      junction or gastric cardia. These patients should, in the absence of tumour
      positive lymph nodes at or proximal to the carina, undergo a transhiatal
      resection to minimise peri-operative complications. New developments include
      endoscopic resection or minimally invasive oesophagectomy, but these therapies
      should still be considered experimental.

PMID- 15942238
TI  - Acute painful sensory neuropathy with subclinical autonomic dysfunction as a
      presenting feature of Hodgkin's disease.

PMID- 15942239
TI  - Multiple subdural haematomas following lumbar puncture.

PMID- 15942240
TI  - Vasogenic edema in a case of hypercalcemia-induced posterior reversible
      encephalopathy.

PMID- 15942241
TI  - Isolated hypoglossal nerve palsy due to compression by a dissecting vertebral
      artery.

PMID- 15942242
TI  - Unilateral spatial neglect related to a depressed skin flap following
      decompressive craniectomy.

PMID- 15942243
TI  - Matrix metalloproteinase-9, its tissue inhibitor(TIMP)-1 and CRP in Alzheimer's
      disease.

PMID- 15942244
TI  - Neurological eponyms derived from literature and visual art.
AB  - Eponyms are common in medicine, and neurology is not an exception. Most
      neurological eponyms originate from the names of those who first described a
      disease or pathological condition, as well as from the names of characters from
      the literature and mythical or biblical heroes. The article describes en block
      both widespread and nowadays seldom used or even forgotten neurological eponyms
      derived from literature and visual art.

PMID- 15942245
TI  - Herpetic lumbosacral radiculoneuropathy in patients with human immunodeficiency
      virus infection.
AB  - We report 4 cases of human immunodeficiency virus infection associated with
      lumbosacral radicular dysfunction and urinary retention. Three of these cases had
      the so-called Elsberg syndrome in that their symptoms were associated with
      genital herpes. In 1 case, different herpes simplex virus types were isolated
      from the cerebrospinal fluid and genital swabs. Lumbosacral radiculoneuropathy
      with urinary retention caused by herpes viruses can develop not only with an
      initial genital herpes infection, but also due to reactivation of a latent herpes
      virus.

PMID- 15942246
TI  - Calcitonin gene-related peptide during sweating in young healthy women.
AB  - Calcitonin gene-related peptide (CGRP) concentrations are increased in
      postmenopausal women and castrated men with symptomatic flushing. We wanted to
      determine if a CGRP increase exists in the plasma of healthy fertile-age women
      during sweating. Plasma concentrations of CGRP were measured by radioimmunoassay
      at maximal sweating during a sauna session and during bicycle exercise both at
      maximal and 70% of maximal work capacity in 8 healthy women of fertile age.
      Plasma concentrations of CGRP were unaffected (>90% statistical power) during
      both experimental sessions. We suggest that sweating itself does not explain the
      rise in CGRP concentrations observed in flushing postmenopausal women.

PMID- 15942247
TI  - MRI for diagnosis of adenomyosis: unsung and underutilized.

PMID- 15942248
TI  - Determinants of circulating adiponectin in women with polycystic ovary syndrome.
AB  - BACKGROUND AND AIM: Adiponectin is regarded as a possible link between adiposity
      and insulin resistance. Ghrelin and leptin are considered as signals of energy
      status. We evaluated the relationships between these peptides, androgens and
      insulin sensitivity in women affected by polycystic ovary syndrome. METHODS:
      Thirty-six women with PCOS were examined with euglycemic hyperinsulinemic clamp
      (to determine M/I, index of insulin sensitivity). Leptin, ghrelin, adiponectin,
      androgens, and SHBG were determined. Statistics was done using correlation
      analysis and backward stepwise multiple regression. RESULTS: The positive
      correlation of adiponectin with testosterone remains significant even after
      adjustment for BMI (p = 0.01), M/I (p = 0.009) and for both M/I and BMI (p =
      0.02). In multiple regression with testosterone, M/I, leptin and ghrelin as
      independent variables, the model including testosterone (p = 0.03) and ghrelin (p
      = 0.002) explained 49% of the variability (p < 0.0012) of adiponectin.
      CONCLUSIONS: Both adiponectin and ghrelin can be involved in the pathophysiology
      of PCOS but their relation must be delineated further.

PMID- 15942249
TI  - Evidence and implications for multiplicative interactions among loci predisposing
      to human common disease.
AB  - OBJECTIVE: The aim of this study was to utilize information on monozygotic twin
      concordance rates and linkage studies results for common diseases to predict the
      likely mode of interaction between susceptibility loci. METHODS: We calculated
      combinations of allele frequency and genotypic relative risk (GRR) that would
      generate linkage results typically observed in common human diseases. Given these
      single locus effects, we calculated the expected monozygotic twin concordance
      assuming different numbers of loci under different interaction models. RESULTS:
      We demonstrate that, for disorders like schizophrenia, a purely additive model of
      interaction among loci is not consistent with the available evidence. Instead
      there are likely significant multiplicative or stronger interactions. Given these
      interactions, we show that in a diagnostic test based on a subset of predisposing
      loci, the marginal increase of predictive value rises with each additional locus
      that is discovered. Our model was consistent with susceptibility alleles being
      common or rare. CONCLUSIONS: Evidence from monozygotic twin concordance rates and
      linkage results point to a significant degree of multiplicative interaction among
      loci.

PMID- 15942250
TI  - Clinical epidemiology of cardiovascular disease in chronic kidney disease.
AB  - Cardiovascular disease (CVD) is the most common cause of death in patients with
      chronic kidney disease (CKD) and end-stage renal disease (ESRD). The clinical
      epidemiology of CVD in CKD is challenging due to a prior lack of standardized
      definitions of CKD, inconsistent measures of renal function, and possible
      alternative effects of 'traditional' CVD risk factors in patients with CKD. These
      challenges add to the complexity of the role of renal impairment as the cause or
      the consequence of cardiovascular disease. The goal of this review is to
      summarize the current evidence on: (1) the incidence and prevalence of CVD in
      chronic renal insufficiency and in ESRD, (2) risk factors for CVD in CKD, (3) the
      outcomes of patients with renal failure with CVD, and (4) CKD as a risk factor
      for CVD. The epidemiological associations implicating the huge burden of CVD
      throughout all stages of CKD highlight the need to better understand and
      implement adequate screening, and diagnostic and treatment strategies.

PMID- 15942251
TI  - Treatment of uremic hyperparathyroidism with percutaneous ethanol injection.
AB  - The percutaneous ethanol injection (PEI) with ultrasound guidance has been
      suggested for the treatment of patients with hyperparathyroidism who are on
      dialysis, with the aim of selectively treating the parathyroid glands with
      nodular hyperplasia. We present our experience in 25 patients with chronic renal
      failure followed during 13.4 +/- 10.6 months. A decrease in the levels of
      parathormone (PTH) (1,236.32 +/- 129.8 vs. 721.66 +/- 142.24 pg/ml), phosphatemia
      (6.16 +/- 0.35 vs. 4.93 +/- 0.36 mg/dl) and calcium-phosphorous product (60.82 +/
      3.81 vs. 46.47 +/- 3.46 mg2/dl2) was verified. In 56% of patients, PTH levels
      decreased (>50% of the baseline value) and 36% had final values <300 pg/ml.
      Patients in whom ultrasound showed a single gland responded better than those
      with more than one gland (83.3 vs. 30.8% of responders in each group). The
      procedures performed had a 4.9% complication rate: hematoma, symptomatic
      hypocalcemia, temporary paresis of the vocal cords. In summary, treatment with
      PEI is useful for the management of patients with hyperparathyroidism who are on
      dialysis, and the results achieved are better in patients who have a single gland
      identified by ultrasonography.

PMID- 15942252
TI  - Serious consequences to the use of cephalosporins as the first line of
      antimicrobial therapy administered in hemodialysis units.
AB  - BACKGROUND: The dramatic spread of vancomycin-resistant enterococci (VRE) among
      hemodialysis (HD) patients led to the replacement of vancomycin with
      cephalosporins as part of the primary empiric therapy for bacterial infections in
      HD units. The aim of the study was to examine the effects of this new regimen on
      the colonization rate of resistant bacteria among HD patients. METHODS: Rectal
      swabs were taken from 105 HD patients and 91 control hospitalized patients.
      Groups were matched for age, sex, nursing home residency and background diseases.
      Enterococci were tested for vancomycin resistance, Staphylococcus aureus isolates
      were tested for methicillin resistance (MRSA), and Enterobacteriaceae were tested
      for extended-spectrum beta-lactamase (ESBL) activity. RESULTS: In the HD group 1
      VRE, 1 MRSA and 9 ESBL-producing organisms were isolated compared to 1 MRSA and 1
      ESBL organism in the control group (p = 0.018 for ESBL). In the year prior to the
      study, the use of cephalosporins had been enhanced in the HD group compared to
      the control group (p < 0.001), and in the HD ESBL-positive patients compared to
      the HD ESBL-negative ones (p = 0.007). The overall use of antibiotics in the
      control group was the same as in the HD group. In a subanalysis of the HD group
      alone, the ESBL carriers were older, sicker, used more antibiotics, were
      hospitalized frequently and had a higher mortality rate, compared to noncarriers.
      CONCLUSIONS: The use of cephalosporins as first-line therapy in HD patients in
      central Israel reduced the prevalence of VRE colonization but may have
      contributed to the emergence of ESBL-producing organisms through induction of
      selection pressure. This may lead to serious complications in the management of
      these patients.

PMID- 15942253
TI  - Cyclosporine prolongs delayed graft function in kidney transplantation: are
      rabbit anti-human thymocyte globulins the answer?
AB  - BACKGROUND: Cyclosporine (CsA) nephrotoxicity may prolong duration of anuria in
      renal transplant patients with delayed graft function (DGF). Thus, many
      Transplant Centers tend to delay CsA treatment in order to accelerate renal
      function recovery. METHODS: In this single-center, retrospective analysis we
      compared the outcomes of 40 renal transplant patients with DGF given a CsA-based
      (n = 17) regimen since the day of transplant or a CsA-sparing regimen (n = 23)
      based on early treatment with rabbit anti-human thymocyte globulin (RATG) and
      delayed CsA administration. We studied all patients with DGF who received a first
      or second graft at the Bergamo Transplant Center from January 1992 to March 2000.
      RESULTS: Patients given RATG as compared to those on CsA had significantly
      shorter duration of anuria (11.0 +/- 5.6 vs. 19.6 +/- 8.9 days; p < 0.005) and of
      initial hospitalization (17.4 +/- 4.3 vs. 27.4 +/- 10.4 days; p < 0.001).
      Throughout the whole study period, 4 patients on RATG as compared to 6 on CsA had
      an acute rejection episode (p > 0.05). However, no patient on RATG as compared to
      4 on CsA had an acute rejection during the anuria period (p < 0.05). Costs
      including hospitalization, dialysis treatment and study drugs were significantly
      lower in RATG than in CsA patients (EUR 29,944 +/- 7,281 vs. 36,795 +/- 13,656; p
      < 0.05). CONCLUSIONS: In renal transplant patients with DGF, early RATG treatment
      with delayed CsA administration accelerated renal function recovery and patient
      discharge, prevented occult rejections throughout the anuria period and
      significantly decreased the treatment costs.

PMID- 15942254
TI  - Serum IgA/C3 ratio may be a useful marker of disease activity in severe Henoch
      Schonlein nephritis.
AB  - BACKGROUND/AIMS: This study was designed to investigate whether the serum IgA/C3
      ratio can be a serologic marker of disease activity in children with severe
      Henoch-Schonlein nephritis (HSN). METHODS: Twelve HSN patients who were treated
      with steroids and cyclosporine were examined. The levels of serum IgA and C3 were
      measured using an international reference preparation (IFCC/CRM470) and a renal
      biopsy was performed in all patients before and after therapy. After therapy,
      patients were divided into 3 groups: complete remission (n = 6, group I), mild
      urinary abnormalities (n = 3, group II), and active renal disease (n = 3, group
      III). RESULTS: The serum IgA/C3 ratio decreased significantly in groups I and II
      after therapy (2.62 +/- 0.82 vs. 2.02 +/- 0.52, p = 0.02), whereas the ratio in
      group III increased, although it was not statistically significant (2.13 +/- 0.93
      vs. 4.67 +/- 1.71, p = 0.25). A follow-up renal biopsy revealed that the activity
      index was reduced in groups I and II (7.0 +/- 2.4 vs. 3.6 +/- 1.6, p = 0.016),
      and not changed in group III (7.3 +/- 2.1 vs. 9.3 +/- 2.5, p = 0.25). The
      activity index at a follow-up renal biopsy correlated positively with the changes
      of the serum IgA/C3 ratio: posttherapy activity index = 1.20 x DeltaIgA/C3 + 4.78
      (r = 0.635, p = 0.027); where DeltaIgA/C3 is posttherapy IgA/C3--pretherapy
      IgA/C3. CONCLUSION: These findings suggest that the serum IgA/C3 ratio may be a
      useful marker to predict disease activity and histologic severity in HSN.

PMID- 15942255
TI  - Transforming growth factor-beta1 SNPs: genetic and phenotypic correlations in
      progressive kidney insufficiency.
AB  - Associations have been described between polymorphisms of cytokine and growth
      factor genes and susceptibility to, or progression of, an increasing number of
      diseases. TGF-beta1 plays an important role in the pathogenesis of experimental
      and clinical glomerulosclerosis and tubulointerstitial fibrosis. In this study,
      single nucleotide polymorphisms (SNPs) in the TGFbeta1 gene were investigated as
      possible markers for the progression of chronic kidney failure (CKF). 145
      Caucasian patients with CKF were screened for four TGFbeta1 SNPs: T-509C in the
      promoter region; Arg25Pro and Leu10Pro in exon 1 and Thr263Ile in exon 5. There
      were significant differences between CKF patients and controls in allele
      frequencies of two of the SNPs, Leu10Pro (p = 0.038) and C-509T (p = 0.02) and in
      haplotype distributions (p = 0.0175), indicating an association with
      susceptibility to CKF. We also observed a significant association between
      progression of CKF and homozygosity for Arg25 (odds ratio 3.77, 95% confidence
      interval 1.57-9.04, p = 0.002). Homozygosity for Arg25 was also associated with
      severity of proteinuria at diagnosis (p = 0.038), plasma TGF-beta1 protein levels
      (p = 0.01), and severity of glomerulosclerosis (p = 0.04). Homozygosity for -509T
      was associated with severity of proteinuria at diagnosis (p = 0.0017), level of
      renal tubular TGF-beta1 immunostaining (p = 0.0006) and with severity of renal
      interstitial inflammatory cellular infiltration (p = 0.01). Tubular TGF-beta1
      immunostaining was significantly higher in biopsies with inflammatory cellular
      infiltration compared those without inflammation (p = 0.0048). There was a
      significant difference in haplotype distributions between CKF patients with
      progressive, as opposed to non-progressive disease (p = 0.0484). TGFbeta1 SNPs
      may be useful prognostic indicators for the progression of CKF.

PMID- 15942256
TI  - Thrombin is a pro-fibrotic factor for rat renal fibroblasts in vitro.
AB  - BACKGROUND: Generation of thrombin occurs in response to parenchymal injury.
      Thrombin not only converts plasma fibrinogen into an insoluble fibrin clot, but
      also potentially augments inflammation through receptor-mediated activity. This
      study examines whether thrombin may potentially exacerbate fibrosis by
      upregulating the function of interstitial fibroblasts in vitro. METHODS:
      Fibroblasts were isolated by explant outgrowth culture of rat kidneys.
      Subcultured cells were grown in DMEM+10% FCS supplemented with 0.1-0.5 U/ml
      thrombin. Functional parameters examined included kinetics (thymidine
      incorporation and change in cell number), differentiation (Western blotting for
      alpha-smooth muscle actin; alphaSMA), expression of procollagen alpha1(I)
      (Northern blotting) and contraction of collagen I lattices. RT-PCR was used to
      characterise expression of protease-activated receptors (PAR) previously
      implicated in thrombin's cellular effects. RESULTS: Cell population growth was
      increased 66 +/- 41 and 47 +/- 41% by 0.1 and 0.5 U/ml thrombin respectively
      (both p < 0.05 vs. basal). Likewise, 0.5 U/ml thrombin increased corrected
      procollagen alpha1(I) expression 2.4-fold (p < 0.05 vs. basal) and exacerbated
      the ability of fibroblasts to contract collagen matrix (p < 0.05 vs. basal).
      These effects were not associated with any change in expression of the
      myofibroblast marker alphaSMA. Effects on cell number were inhibited by treatment
      with (D)-Phe-Pro-Arg-chloromethylketone HCl (PPACK) suggesting that functional
      effects were mediated by serine protease activity. PAR-1 was the only fully
      functional known thrombin receptor expressed by these cells. CONCLUSION: Thrombin
      is a potential unrecognised fibroblast agonist in renal disease. Further studies
      of thrombin and its receptors may yield valuable insights into the pathogenesis
      of interstitial fibrosis.

PMID- 15942257
TI  - Dietary caffeine, performance and mood: enhancing and restorative effects after
      controlling for withdrawal reversal.
AB  - This study aimed to determine whether sustained (i.e. dietary) use of caffeine
      has net effects on performance and mood compared with sustained abstinence, and
      whether dietary caffeine restores performance and mood adversely affected by
      sleep restriction. Participants (n = 96) alternated weekly between ingesting
      placebo and caffeine (1.75 mg/kg) three times daily for 4 consecutive weeks,
      while either rested or sleep restricted. Performance involved either a single
      task requiring sustained vigilance or a varied battery of brief psychomotor and
      cognitive tasks, and mood was assessed using the Profile of Mood States. Caffeine
      had no significant net enhancing effects for either performance or mood when
      participants were rested, and produced no net restorative effects when
      performance and mood were degraded by sleep restriction.

PMID- 15942258
TI  - Ghrelin plasma levels during psychopharmacological treatment.
AB  - The mechanisms underlying weight gain induced by psychopharmacological agents are
      poorly understood. Because the recently discovered enteric hormone, ghrelin,
      stimulates food intake, we hypothesized that increases in circulating ghrelin
      levels might mediate the weight gain caused by certain antidepressants and
      atypical antipsychotic drugs. Fifty-two patients receiving psychopharmacological
      treatments were included in the study: 16 patients received antidepressants that
      are not known to induce weight gain, and 13 patients received mirtazapine or
      trimipramine, which are antidepressants known to lead to weight gain; 6 patients
      received clozapine and olanzapine, which have the highest liability among the
      antipsychotics to cause weight gain, and 17 patients received other
      antipsychotics. Fasting venous blood samples for the measurement of ghrelin were
      drawn in the morning between 06:00 and 08:00 a.m. in the second week of
      treatment. Although psychopharmacological treatment induced significant weight
      changes in the expected directions (most prominent in the clozapine or olanzapine
      treatment group), ghrelin levels did not differ significantly between groups.
      Psychotropic drugs with different propensities to induce body weight gain are
      associated with similar concentrations of plasma ghrelin in psychiatric patients
      after a short period of treatment.

PMID- 15942259
TI  - Investigating the effects of estradiol or estradiol/progesterone treatment on
      mood, depressive symptoms, menopausal symptoms and subjective sleep quality in
      older healthy hysterectomized women: a questionnaire study.
AB  - Clinical studies have documented that estrogen treatment often ameliorates mood
      disturbances and depressive symptoms occurring during the menopausal transition.
      The relevance of gonadal hormones for mood and well-being in healthy older
      nondepressed women is less well understood. Fifty-one healthy hysterectomized
      women (mean age 64) participated in a placebo-controlled double-blind study on
      the effects of gonadal hormones on cognition. They received either estradiol (2
      mg estradiol valerate), estradiol plus progesterone (100 mg micronized
      progesterone) or placebo. Mood, well being, menopausal symptoms, depressive
      symptoms and subjective sleep quality were measured at baseline and after 4 and
      24 weeks of treatment using three questionnaires. Thirty-five women could be
      included into the final analysis. Strong increases in estradiol and progesterone
      levels occurred in response to the treatment. The two hormones, however, had no
      effects on mood, well-being, menopausal symptoms, sleep quality and depressive
      symptoms. The current small study suggests that older healthy nondepressed
      hysterectomized women do not react with positive or negative mood changes to
      estradiol or estradiol/progesterone treatment.

PMID- 15942260
TI  - On the waveform of the acoustic startle blink in the paradigm of prepulse
      inhibition - methodological and physiological aspects.
AB  - Recent studies suggest that the eye blink response to intense acoustic stimuli
      consists of two components that may occasionally result in waveforms with two
      peaks. In the present study, the prevalence, peak latencies, and peak magnitudes
      in responses exhibiting one or two peaks were investigated in healthy subjects in
      25 pulse-alone and 25 prepulse-pulse trials using an interstimulus interval of 60
      ms. Electromyographic activity was recorded simultaneously from the orbicularis
      oculi muscle (OOM) and from the sternocleidomastoid muscle (SCM) to explore the
      temporal relationship of the peaks to the generalized startle reaction. Responses
      in the OOM occurred with shorter onset and peak latencies than the responses in
      the SCM. In about 30% of pulse-alone trials, OOM responses exhibited two peaks
      that showed similar prepulse inhibition. These findings support the view that
      both components of the acoustically evoked OOM response exhibit similar
      plasticity in the paradigm of prepulse inhibition.

PMID- 15942261
TI  - Serotonin dysfunction and suicide attempts in major depressives: an auditory
      event-related potential study.
AB  - BACKGROUND: Serotonergic dysfunction is believed to be involved in suicide
      attempts. The loudness-dependent auditory evoked potential (LDAEP) is one of the
      validated indicators of the activity of the central serotonin system in humans.
      OBJECTIVES: This study was designed to investigate possible differences in the
      LDAEP and P300 between those depressed patients who attempted suicide and those
      who did not. METHODS: The LDAEP and P300 levels were recorded for 66 depressive
      patients (among which 16 had attempted suicide). RESULTS: Those who had attempted
      suicide showed a sharper slope of the LDAEP and increased frontal P300 amplitude.
      A high correlation between the LDAEP and P300, and a gender difference were also
      noted. CONCLUSIONS: Our results are concordant with previous assumptions about
      serotonin dysfunction in depressives who attempt suicide.

PMID- 15942262
TI  - Anhedonia and substance-related symptoms in detoxified substance-dependent
      subjects: a correlation study.
AB  - Anhedonia is a condition in which the capacity of experiencing pleasure is
      totally or partially lost, frequently occurring in mood disorders, as a negative
      symptom in schizophrenia, and in substance use disorders. In order to test a set
      of instruments for anhedonia in a population of detoxified opiate, alcohol and
      multiple substance-dependent subjects, 70 individuals were recruited from three
      different clinical settings. The following scales were applied: Snaith-Hamilton
      Pleasure Scale (SHAPS), Bech-Rafaelsen Melancholia Scale (BRMS), Scale for the
      Assessment of Negative Symptoms (SANS), specific withdrawal scales, and visual
      analogue scales (VAS) for hedonic capability and substance craving. The scales
      measuring anhedonia either directly (SHAPS, VAS for hedonic capability) or in
      some key items (SANS, BRMS) were significantly correlated with each other. The
      period of time since detoxification was inversely correlated with anhedonia and
      withdrawal symptomatology. Craving was positively correlated with anhedonia. Out
      of the total sample, only 18.5% could be defined as psychometrically anhedonic.
      The same correlations were found in this subsample. The composite instrument
      employed for assessing anhedonia and hedonic capability was found to be sensitive
      enough to detect such a dimension in the population considered, with the single
      scales significantly interrelated. In conclusion, we found interrelations between
      hedonic capability, craving and protracted withdrawal, particularly in opiate
      dependent subjects. The strongest association occurred between hedonic capability
      and craving.

PMID- 15942263
TI  - Increased and decreased cortical reactivities in novelty seeking and persistence:
      a multichannel near-infrared spectroscopy study in healthy subjects.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) has enabled completely noninvasive
      measurements of regional cerebral blood volume (rCBV) changes in cortices. In the
      present study, we investigated the relationships between rCBV changes assessed
      with NIRS and two dimensions of personality, novelty seeking and persistence.
      METHODS: Thirty right-handed healthy volunteers participated in the study. Their
      personality traits were assessed using the Temperament and Character Inventory
      (TCI), and changes in oxy- and deoxy-hemoglobin concentrations were monitored
      during 40 s unilateral finger tapping tasks over the subjects' bilateral temporal
      regions using a 24-channel NIRS machine. RESULTS: The oxy-hemoglobin
      concentration increases were significantly correlated positively with novelty
      seeking scores and negatively with persistence scores in the TCI during the
      initial time segment of the left-finger tapping task. CONCLUSION: Increased and
      decreased brain activations demonstrated using multichannel NIRS were assumed to
      characterize the cortical reactivities underlying novelty seeking and persistence
      temperament, respectively.

PMID- 15942264
TI  - Genotype-phenotype correlation in Italian families with Stargardt disease.
AB  - Autosomal recessive Stargardt disease (STGD) has been associated with substantial
      genetic and phenotypic heterogeneity. By systematic clinical analyses of STGD
      patients with complete genetic data (i.e. identified mutations on both alleles of
      the ABCA4 gene), we set out to determine phenotypic subtypes and to correlate
      these with specific ABCA4 alleles. Twenty-eight patients from 18 families with
      STGD/fundus flavimaculatus were investigated. All patients were submitted to
      complete ophthalmologic examination, electrophysiology, fluorescein angiography
      and ABCA4 gene chip analysis. Two main clinical phenotypes were observed among
      the examined patients. The severe phenotype was characterized by the onset of the
      disease <20 years and reduced ERG response, whereas the mild phenotype presented
      with later onset of the disease and a normal ERG response. Genetic analysis of
      the ABCA4 gene revealed, in the severe group, more frequently deletions, stop
      codons and insertions as compared to the mild phenotype group (p=0.0113 by
      Fisher's exact test). Moreover, the compound heterozygous mutations
      G1961E/5018+2T-->C found in 7 patients from 3 unrelated STGD families were
      associated with a mild phenotype in all subjects, except 1. This study documented
      variability of the clinical expression of STGD in relation to the age of onset of
      the disease, fundus appearance and the ERG response and allowed to subdivide
      patients into a severe and a mild phenotype group. These findings suggest that an
      extensive and comprehensive genetic analysis of STGD patients combined with
      thorough clinical evaluation, including the careful recording of the age of onset
      of the disease, would allow a more precise prognostic evaluation.

PMID- 15942265
TI  - The efficacy of intravitreal piperacillin/tazobactam in rabbits with experimental
      Staphylococcus epidermidis endophthalmitis: a comparison with vancomycin.
AB  - BACKGROUND: To investigate the efficacy of intravitreal piperacillin/tazobactam
      in rabbit eyes with experimental S. epidermidis endophthalmitis and to compare
      the outcomes with intravitreal vancomycin application. MATERIAL AND METHODS:
      Twenty-four New Zealand white albino rabbits were divided into three equal groups
      (n=8 in each), and the right eyes received 0.1-ml intravitreal injections of S.
      epidermidis suspension. The left eyes served as uninfected controls and were
      injected with 0.1 ml of saline solution. The right eyes of rabbits in group 1
      were treated with intravitreal injection of 250 microg/0.1 ml
      piperacillin/tazobactam 24 h after intravitreal inoculation of S. epidermidis
      whereas group 2 eyes received intravitreal 1 mg/0.1 ml vancomycin. Group 3 eyes
      received no treatment and served as infected controls. Clinical examination of
      the eyes in each group was performed on the 1st, 3rd and 6th day after the
      inoculation of S. epidermidis. On the 6th day, 0.1-ml vitreous aspirates were
      obtained for microbiological analysis, and then the eyes were enucleated for
      histopathological evaluation. RESULTS: There were no statistically significant
      differences in mean clinical scores between the groups on the first day after S.
      epidermidis inoculation (p>0.05). On the 6th day, the mean clinical score of
      group 3 was significantly higher (p<0.001), but the mean clinical scores of
      groups 1 and 2 were similar (p=0.812). The mean logarithmic value of colony
      forming units per milliliter of groups 1, 2 and 3 were 0.6+/-1.3, 0.5+/-1.5 and
      5.3+/-0.7, respectively. Mean histopathological scores of the groups were 8.3+/
      0.9, 7.5+/-1.3 and 15.6+/-1.2, respectively. Group 3 eyes had significantly more
      colony-forming units per milliliter and a higher histopathological score (for
      each, p<0.001), and there were no statistically significant differences in
      microbiological and histopathological scores between groups 1 and 2 (for each,
      p>0.05). CONCLUSION: Intravitreal application of 250 microg/0.1 ml
      piperacillin/tazobactam seems to be approximately equally effective with
      intravitreal 1 mg/0.1 vancomycin application in the treatment of experimental S.
      epidermidis endophthalmitis. Therefore, intravitreal piperacillin/tazobactam may
      be an alternative therapeutic option in the treatment of S. epidermidis
      endophthalmitis.

PMID- 15942266
TI  - Current concepts in therapy of chronic rhinosinusitis and nasal polyposis.
AB  - The exact pathophysiological mechanisms leading to chronic rhinosinusitis (CRS)
      still to a large extent remain obscure. However, recently there has been some
      progress in elucidating the etiology of nasal polyposis, especially regarding
      tissue eosinophilia as well as the role of aspirin intolerance and eicosanoid
      mediators. Endonasal sinus surgery has evolved to be the treatment of choice in
      CRS and nasal polyposis in all cases where conservative treatment has failed or
      resulted in only a partial or temporary relief. Today, state of the art in
      surgical technique includes the ability to combine microscopic and endoscopic
      procedures. Regardless of technical advances like powered instrumentation or
      computer-aided surgery, in a modern protocol, surgical therapy can offer only one
      option within a complex and individually tailored therapeutical concept. This
      review discusses current concepts and new developments in the diagnosis and
      treatment of CRS and nasal polyposis.

PMID- 15942267
TI  - Second branchial anomalies in children.
AB  - AIM: The aim of this study was to evaluate the data of our patients who had been
      treated for second branchial anomalies in the last 10 years. Here we report our
      clinical experience in second branchial anomalies with a review of the
      literature. PATIENTS AND METHODS: We evaluated retrospectively the data of 14
      patients, who had been operated on between 1994 and 2004 for second branchial
      anomalies, in relation to age, sex, complaint at application, diagnostic test,
      surgical procedures and histopathologic findings. RESULTS: The mean age of the
      patients (8 female, 6 male) was 5.3 years (range = 1.5-16). The anomalies were
      usually located on the left side of the neck (n = 6). There were only 3 cases
      with bilateral anomalies. The majority of the lesions were sinuses (93%). The
      most frequent clinical feature was the presence of persistent discharge from an
      external (cutaneous) orifice. All lesions were excised by performing a second
      step ladder incision. Eight of the lesions were removed under the guidance of 3/0
      polypropylene suture. No postoperative complication or recurrence was observed
      during the follow-up period. CONCLUSIONS: Second branchial arches anomalies are
      the most common branchial anomalies. Sinuses are more frequently encountered in
      children. Definitive treatment for these lesions is surgical excision. A
      polypropylene suture can be inserted into the tract as a guide to prevent
      incomplete excision.

PMID- 15942268
TI  - History of the European pancreatic club: the first 40 years 1965-2005. The
      development of the European pancreatic club as a scientific society.
AB  - The European Pancreatic Club (EPC) was founded during a first symposium on
      December 9 and 10, 1965 in London (President H.T. Howat). The nine founding
      members were one biochemist (Jean Christophe, Belgium), one physiologist (Alfred
      A. Harper, UK), two surgeons (Andre Delcourt, Belgium, Yngve Edlund, Norway) and
      five physicians with special interest in the pancreas (Werner Creutzfeldt,
      Germany, Oliver Fitzgerald, Ireland, Karel Herfort, Czechoslovakia, Henry T.
      Howat, UK, Henri Sarles, France). It was the first scientific society worldwide
      which was concerned with the study of the pancreas. The idea was to bring basic
      scientists and clinicians together in an informal atmosphere to promote
      friendship and communication on research between them. The 2nd symposium was held
      in Marseilles in 1967 (President H. Sarles). Until now there have nearly always
      been annual meetings, the one in 2005 is the 37th. In 1973 the EPC decided to lay
      down 'Internal Rules' and in 1992 new statutes were introduced. It became a
      member of the United European Gastroenterology Federation (UEGF) and is
      coorganizer of the United European Gastroenterology Week (UEGW). The official
      journal has been Pancreatology since 2001; previously the abstracts had been
      printed in Digestion since 1982. The officers of the EPC are the President, the
      Past President, the President Elect, the Secretary, the Treasurer and six
      Councillors from different European countries, three from basic and three from
      clinical science. A selection committee (4 basic and 4 clinical scientists)
      decides on the acceptance of papers. Officers and Presidents are elected by the
      General Assembly. At the meetings on average 150 contributions are accepted for
      presentation; the abstracts are printed in Pancreatology. Papers came from nearly
      all European countries and from overseas. In numbers Germany, France, the UK,
      Italy and Sweden are at the top. In total 4,837 scientific presentations were
      made from 1971 to 2004. Fifty-nine symposia and 245 invited lectures informed
      about the state of the art. Since 1991 a Young Researchers Corner given by
      international experts is especially designed to give information on new
      techniques of research. The European Study Group of Pancreatic Cancer (ESPAC) and
      the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer
      (EUROPAC) are affiliated with the EPC. Since 1999 a Newsletter of the EPC has
      been published. The website of the EPC is www.e-p-c.org.

PMID- 15942269
TI  - History of the European pancreatic club: the first 40 years 1965-2005. The
      scientific profile of the European pancreatic club and what stood the test of
      time.
AB  - The invited lectures, the symposia and panels and the printed abstracts of the
      meetings are the basis for analysis of the development of pancreatic research
      over the 40 years from 1965 to 2005. 245 invited lectures and 59 symposia, panels
      and round tables presented and discussed the latest state of the art at the
      meetings of the European Pancreatic Club (EPC). We analyze in detail the
      contributions to physiology and biochemistry of the pancreas, the neurohormonal
      control of pancreatic secretion, cell biology, stimulus-secretion coupling, and
      cell receptors. The research on the endocrine-exocrine relationship, nutrition
      and the pancreas, experimental and clinical acute and chronic pancreatitis,
      function tests and imaging of the pancreas, pancreatic development and growth,
      experimental and clinical pancreatic carcinoma, genetics and inherited pancreatic
      diseases over the years are listed in special sections and discussed. At the
      center of the EPC meetings there are scientific sessions with either oral or
      poster presentations. From 1971 to 2004, 4,837 contributions were accepted and
      printed as abstracts. In the first 30 years papers on basic research usually
      amounted to around 30-40%, on pathophysiology also 20-40% and the rest were on
      clinical work. In the years since 1993 the basic contributions became less with
      20% and even only 10% of all papers in the last years. Abstracts from
      pathophysiology and pathology increased in the 1990s, mainly with work on
      pancreatic carcinoma. Papers on clinical topics also rose to 40-50% of all in the
      years since 1998. The interest in clinical topics shifted over the years. Chronic
      pancreatitis was the main topic in the 1970s; in the 1980s until 2000, acute
      pancreatitis gained more interest, and pancreatic cancer is now an attractive
      field of study due to new methods of research with cancer cell lines and genetic
      models. Since 1993 a Young Researchers Corner with international experts is
      offered at the meetings of the EPC, the programs are analyzed. In the last
      section the question of 'what stood the test of time?' is asked as reflected in
      40 years of meetings of the EPC. Topics are physiology, biochemistry and cell
      biology in relation to the pancreas, pathogenesis of acute and chronic
      pancreatitis, methods of diagnosis, treatment of pancreatitis and of carcinoma.

PMID- 15942272
TI  - Effect of olopatadine and other histamine H1 receptor antagonists on the skin
      inflammation induced by repeated topical application of oxazolone in mice.
AB  - Histamine H1 receptor antagonists have long been prescribed for atopic dermatitis
      as an adjuvant therapy with topical therapy by local applied steroids.
      Olopatadine is one of the second-generation histamine H1 receptor antagonists
      that are treated for allergic disorders. We investigated that the effect of
      olopatadine on oxazolone-induced chronic contact hypersensitivity response in
      BALB/c mice compared with other histamine H1 receptor antagonists loratadine,
      cetirizine and fexofenadine. The chronic contact hypersensitivity induced by
      repeated application of oxazolone was treated with olopatadine and other
      histamine H1 receptor antagonists at the effective doses on histamine-induced paw
      edema in mice. The effects of these drugs in the oxazolone-induced model were
      quantified by measurements of ear swelling, and levels of cytokines in the
      lesioned ear. Olopatadine significantly inhibited the ear swelling and the
      increased production of IL-4, IL-1beta, IL-6, GM-CSF and NGF in the lesioned ear.
      On the other hand, the other histamine H1 receptor antagonists did not
      significantly suppress the increase in ear thickness. Moreover, they did not
      affect the production of cytokines in the lesioned ear. These results indicate
      that olopatadine appears to exert additional biological effects besides its
      blockade of the histamine H1 receptor.

PMID- 15942273
TI  - Low extracellular Cl- environment attenuates changes in intracellular pH and
      contraction following extracellular acidosis in Wistar Kyoto rat aorta.
AB  - This study was conducted to investigate the influence of extracellular Cl- ([Cl
      ]o) on the intracellular pH (pHi) regulation and the contractile state of the
      isolated aorta from Wistar Kyoto (WKY) rats. Isometric tension recording and
      fluorometry techniques were utilized to measure contractile response and pHi in
      isolated aortic strips. Decreasing extracellular pH (pHo) from 7.4 to 6.5
      produced a marked contraction, which was 75.8 +/- 5.6% of the 64.8 mmol/l KCl
      induced contraction. The acidosis-induced contraction was significantly
      attenuated in low [Cl-]o solution, the magnitude of which was 56.0 +/- 3.0% of
      the 64.8 mmol/l KCl-induced contraction. Decreasing pHo of the normal solution to
      6.5 rapidly decreased pHi in aortic smooth muscle cells and produced a
      corresponding contraction. When the pHo was decreased in low [Cl-]o solution, a
      rapid fall in pHi followed by reversal of pHi changes, in a time-dependent manner
      was observed, despite low pHo. Omission of HCO3- from the low [Cl-]o solution
      restored the contractile response to acidosis, which was comparable to that in
      normal solution. Similarly, following decrease in pHo to 6.5, no recovery of
      intracellular acidosis was observed. We conclude that low [Cl-]o environment
      causes activation of extracellular HCO3- -dependent pHi-regulating mechanism,
      that results in the rapid recovery of pHi following acidosis, and the attenuation
      of acidosis-induced contraction of WKY aorta.

PMID- 15942274
TI  - Cardioprotective effects of [5-(2-methyl-5-fluorophenyl)furan-2
      ylcarbonyl]guanidine (KR-32568) in an anesthetized rat model of ischemia and
      reperfusion heart injury.
AB  - The effects of a novel sodium/hydrogen exchanger-1 (NHE-1) inhibitor, KR-32568,
      were studied in an anesthetized rat model of 30 min ischemia/2.5 h reperfusion
      heart injury. KR-32568 dose-dependently inhibited NHE-1-mediated rabbit platelet
      swelling induced by intracellular acidification. In our anesthetized rat model,
      KR-32568 reduced infarct size from 67 (control) to 43 and 24% at 0.1 and 1.0
      mg/kg (i.v. bolus, given 10 min before ischemia), respectively. KR-32568 at the
      same doses also significantly reduced the total number of ventricular premature
      beats during ischemia/reperfusion from 530 (control) to 266 and 115 beats,
      ventricular tachycardia (VT) incidence from 51 (control) to 21 and 8, VT duration
      from 238 s (control) to 63 and 33 s, ventricular fibrillation (VF) incidence from
      17 (control) to 8 and 0, and VF duration from 85 s to 18 and 1 s. These results
      indicate that KR-32568 may exert potent cardioprotective effects in rats via
      inhibition of sodium/hydrogen exchanger-1.

PMID- 15942275
TI  - The role of cranial expansion for craniocephalic disproportion.
AB  - The appropriate treatment for craniocephalic disproportion, such as caused by
      slit ventricle syndrome, is uncertain. We have reviewed the treatment and
      outcomes of 4 children who underwent cranial expansion over a period of 5 years.
      The ages at cranial expansion were 16 months, 3 years 6 months and 2 at 6 years.
      Two children had slit ventricle syndrome and were treated with bilateral parietal
      expansions. Two children had non-syndromic craniosynostosis, one of these having
      vitamin D-resistant rickets. The latter 2 were treated with posterior cranial
      vault expansion, and one also had a craniocervical junction decompression
      performed. Post-operatively, symptoms of raised intracranial pressure resolved in
      all cases, and there was radiological evidence of re-establishment of normal CSF
      pathways. Although a rare condition, cranial expansion operations can be
      successful in appropriately selected cases of craniocephalic disproportion.

PMID- 15942276
TI  - Surgical treatment of epilepsy in children caused by focal cortical dysplasia.
AB  - Focal cortical dysplasia (FCD) is a congenital disorder of neuronal migration
      that is increasingly recognized as a common cause of seizures in children,
      occurring in 20-30% of all surgically treated cases of epilepsy in the pediatric
      population. Advances in neuroimaging have contributed to recognition of FCD. We
      report 15 children (9 female, 6 male) with FCD and surgically treated intractable
      epilepsy. In 9 cases, a surgical strategy of anatomic (frameless stereotactic)
      grid placement and physiologic (electrocorticography) resection was employed.
      Postoperative MRI scans were obtained, the pathologic specimen was graded
      according to the Brannstrom system, and seizure outcome was defined using the
      Engel classification. There were no deaths and no permanent morbidity. After, on
      average, 4 years since treatment, 10 children are seizure free, 2 are 2A, 2 are
      2B and 1 is 3A. Predictors of good outcome are an MRI-defined lesion and
      increased cortical disorganization (higher Brannstrom grade). Subtotal resection
      did not preclude a seizure-free outcome.

PMID- 15942277
TI  - Abdominal pseudocyst: predisposing factors and treatment algorithm.
AB  - Abdominal pseudocyst (APC) is an uncommon complication of ventriculoperitoneal
      shunts. Various predisposing factors have been attributed to it, including the
      presence of infection and multiple shunt revisions. We reviewed the records of
      shunt revisions performed over a 20-year period. During that time, 64 cases of
      APC were found in 36 patients. The records were then reviewed for the presence of
      infection, history of necrotizing enterocolitis, prior abdominal surgery, and
      treatment performed. Of the cases of APC, 46 were primary and 18 were recurrent.
      A history of prior abdominal surgery other than shunt revision was found in 47%
      of patients and a history of necrotizing enterocolitis was found in 19% of
      patients. The average number of prior shunt revisions was 4.1 per patient. Shunt
      infection as defined by positive cultures of either cerebrospinal fluid or
      abdominal fluid was present in only 23% of cases of APC. A history of prior shunt
      infection was present in 30% of patients. Infection was treated by shunt removal,
      external ventricular drainage, and appropriate antibiotics. After the infection
      was cleared or if no infection was present, treatment consisted of: (1)
      repositioning the distal catheter into the peritoneum, (2) repositioning the
      distal catheter into the pleural space, the atrium, or the gallbladder, (3)
      exploratory laparotomy with lysis of adhesions and repositioning the peritoneal
      catheter, (4) APC aspiration only, or (5) shunt removal or disconnection. Because
      of the complexity of APC management, we analyzed the outcomes of our cases and
      outlined an algorithm to simplify this process.

PMID- 15942278
TI  - Spinal lipomas in children--surgical management and long-term follow-up.
AB  - Since its introduction, MR imaging has been easy to perform on all children with
      lumbosacral cutaneous stigmata, and has enabled the phenomenal refinement of
      spinal pathology. We investigated the overall outcomes of children with spinal
      lipomas at the Osaka Medical Center and Research Institute for Maternal and Child
      Health in Osaka, Japan. Between 1991 and 2003, 76 children with a tethered cord
      underwent a total of 90 surgical procedures at our institutes. Of this cohort, 67
      cases had spinal lipomas. The mean age of patients at first operation for
      asymptomatic lipoma was 22.4 months (range: 1 month to 16 years, trim mean: 10.1
      months, mode: 5 months), except 4 cases. The mean total follow-up for the cohort
      since the first surgical procedure was 7.2 years (trim mean: 7.9 years). Since
      the introduction of MR imaging, the reoperation rate for symptoms or signs in our
      series was 16.4% (11 cases). Regarding the 13 subsequent reoperations (2 patients
      had 2 operations), 3 patients were reoperated on due to multiplication of the
      lipomas after untethering, 3 due to urologic symptoms and 5 due to orthopedic
      signs. There were 2 cases who also had to undergo reoperation early due to CSF
      leakage. Filum and conus lipomas have similar tethering pathologies, but differ
      in the outcome following surgery. Filum lipomas are benign, and therefore surgery
      is safe and effective. Conus lipomas are more difficult to manage.

PMID- 15942279
TI  - Circumferential cervical spine surgery in an 18-month-old female with traumatic
      disruption of the odontoid and C3 vertebrae. Case report and review of
      techniques. Case report and review of techniques.
AB  - STUDY DESIGN: A case study of an 18-month-old female with craniovertebral
      instability and spinal cord compression requiring circumferential stabilization.
      A review of surgical techniques in upper cervical spine and craniovertebral
      stabilization for young children is provided. OBJECTIVES: To describe an
      interesting surgical approach in a young pediatric patient requiring
      circumferential stability at the craniovertebral junction. BACKGROUND DATA:
      Craniovertebral instability is problematic in the young pediatric population due
      to the inability to secure hardware for stabilization. We present an interesting
      case of spinal cord compression with craniovertebral instability in an 18-month
      old female requiring circumferential cervical spine and craniovertebral
      stabilization. METHODS: The patient presented with acute onset quadriparesis
      after a fall. Radiographs demonstrated C2-C3 disruption with canal compromise.
      Magnetic resonance imaging revealed signal changes of the spinal cord at C2-C3.
      Neurological examination revealed normal muscle volume with strength 1/5 in the
      upper extremities and 0/5 in the lower extremities. Respirations were normal with
      normal diaphragmatic function. Cranial nerves were intact. RESULTS: Halo-traction
      attempted at 0.453 kg induced occipital-atlantal dislocation. The patient
      underwent anterior corpectomy of C3 and the base of C2 with autologous rib grafts
      placed from C2 to C4 and macropore as an anterior plating system. Posteriorly the
      patient had occiput-C3 fusion with a titanium rod and autologous rib grafts
      bilaterally. Postoperatively the patient regained normal neurological function
      with circumferential fusion after 4 months in a halo vest. CONCLUSIONS: This case
      demonstrates the ability to achieve circumferential stabilization in the young
      pediatric patient. Injuries at the odontoid synchondrosis can be difficult to
      treat and are only complicated by having to achieve a posterior fusion at the
      craniovertebral junction. We present a successful case of circumferential fusion
      and offer a surgical technique to achieve spinal cord decompression and fusion of
      the upper cervical spine and craniovertebral junction in the young pediatric
      population.

PMID- 15942280
TI  - Cyanotic breath-holding spell: a life-threatening complication after radical
      resection of a cervicomedullary ganglioglioma.
AB  - Cyanotic breath-holding spell is a benign and self-limiting disease of young
      children but occasionally associated with sudden, unexpected death. The authors
      report a rare case in a 2-year-old girl with a severe form that started after
      radical resection of a cervicomedullary ganglioglioma. She was admitted to our
      hospital because of delayed and unstable gait. Since magnetic resonance imaging
      showed a cervicomedullary tumor, she underwent a radical resection and histology
      showed the tumor to be a ganglioglioma. Postoperatively, the function of the
      lower cranial nerves and cerebellum deteriorated and hemiparesis on the left
      became apparent, but she returned to the preoperative state in a few months. In
      addition, mild sleep apnea (Ondine curse) and severe cyanotic breath-holding
      spells occurred. The former responded to medication but the latter failed and
      continued several times per day with a rapid onset and progression of hypoxemia,
      loss of consciousness, sweating and opisthotonos. Five months after the
      operation, the patient returned home with a portable oxygen saturation monitor
      equipped with an alarm. This case indicates that cyanotic breath-holding spell,
      as well as sleep apnea, is critical during the early postoperative period. This
      is the first report observing that such spells may occur as a complication of
      radical resection of a cervicomedullary tumor.

PMID- 15942281
TI  - An unusual presentation of lumbosacral dermal sinus with CSF leak and meningitis.
      A case report and review of the literature.
AB  - Dermal sinus tracts are common skin manifestations seen with spinal dysraphism.
      Most of these dermal sinus tracts occur in the lumbosacral region. Though dermal
      sinus tracts are a common manifestation, their presentation with CSF leak is rare
      and important as they predispose to recurrent meningitis along with neurological
      deficits. Here we present an interesting case of a 33-month-old female child with
      dermal sinus CSF leak, tethered cord and intradural dermoid who presented with
      meningitis and was treated with excision of the tract, removal of the dermoid and
      detethering of the cord.

PMID- 15942282
TI  - Linezolid for the treatment of a heteroresistant Staphylococcus aureus shunt
      infection.
AB  - The emergence of multidrug-resistant bacteria as the cause of
      ventriculoperitoneal shunt infections is a disconcerting phenomenon that often
      requires the use of alternative antimicrobials due to resistance against commonly
      used agents. The following is a case report describing the successful treatment
      of a ventriculoperitoneal shunt infection caused by a heteroresistant strain of
      Staphylococcus aureus with linezolid. Linezolid may have utility in treating
      pediatric CNS infections due to its tolerability, excellent blood-brain barrier
      penetration, and activity against multiple resistant Gram-positive organisms such
      as S. aureus, vancomycin-resistant Enterococcus faecium and Streptococcus
      pneumoniae.

PMID- 15942283
TI  - Hypothalamic hamartoma in association with a suprasellar arachnoid cyst: a case
      report.
AB  - A 5-year-old female presented with a history of precocious puberty and increased
      height. MRI of the brain revealed a nonenhancing hypothalamic mass and associated
      suprasellar arachnoid cyst. The patient underwent a right frontal craniotomy with
      orbital osteotomy for wide fenestration of the cyst. Intraoperatively, it was
      clear the mass represented a hamartoma with a very smooth glistening surface. For
      this reason, no biopsy of the wall was performed. Postoperatively, the patient
      remains neurologically intact and without any medication dependence. This case
      highlights the occurrence of a suprasellar arachnoid cyst in association with a
      hypothalamic hamartoma.

PMID- 15942284
TI  - Neurocutaneous melanosis and congenital melanocytic nevus in the head.

PMID- 15942285
TI  - Large intracranial mass with a calcified rim - is it a brain abscess?

PMID- 15942286
TI  - Migration of subduroperitoneal shunt into the subdural space: an unusual
      complication.

PMID- 15942287
TI  - Bronchiectasis: abated or aborted?

PMID- 15942288
TI  - Genetics of sarcoidosis: role of co-stimulatory genes?

PMID- 15942289
TI  - Impact of molecular pathology on the clinical management of lung cancer.

PMID- 15942290
TI  - Non-cystic-fibrosis bronchiectasis in children: a persisting problem in
      developing countries.
AB  - BACKGROUND: Non-cystic-fibrosis (non-CF) bronchiectasis in childhood is still one
      of the most common causes of childhood morbidity in developing countries. The
      management of these patients remains problematic, and there are few studies of
      long-term outcome. OBJECTIVE: The aim of this retrospective study was to define
      the general characteristics, underlying causative factors and long-term follow-up
      results of non-CF bronchiectasis patients. METHODS: One hundred and eleven
      consecutive children, diagnosed with non-CF bronchiectasis were included in the
      study. General characteristics and underlying causes were recorded from the
      medical records. Clinical outcomes were evaluated in terms of lung function
      tests, annual exacerbation rates and patient/parent perception of health status.
      RESULTS: Mean age of the patients was 7.4 +/- 3.7 years at presentation, and
      patients had been followed 4.7 +/- 2.7 years on average. In 62.2% of the
      patients, an underlying etiology was identified, whereas postinfectious
      bronchiectasis was the most common (29.7%). In spite of intensive medical
      treatment, 23.4% of the patients required surgery. The annual lower respiratory
      infection rate has decreased from a mean of 6.6 +/- 4.0 to 2.9 +/- 2.9 during
      follow-up (p < 0.0001). Lung function tests were also found to be improved (mean
      FEV1% 63.3 +/- 21.0 vs. 73.9 +/- 27.9; p = 0.01; mean FVC% 68.1 +/- 22.2 vs. 74.0
      +/- 24.8; p = 0.04). There was clinical improvement in both the surgical (73%)
      and medical (70.1%) groups (p > 0.05). CONCLUSION: In conclusion, bronchiectasis
      remains a disease of concern to pediatricians, particularly in developing
      countries. Infections are still important causes of bronchiectasis, and clinical
      improvement can be achieved by appropriate treatment. Although medical treatment
      is the mainstay of management, surgery should be considered in selected patients.

PMID- 15942291
TI  - Airway clearance in bronchiectasis: a randomized crossover trial of active cycle
      of breathing techniques versus Acapella.
AB  - BACKGROUND: The efficacy of a new airway clearance device (Acapella) has not been
      previously investigated. Active cycle of breathing techniques (ACBT) is the
      standard airway clearance technique used in patients with bronchiectasis.
      OBJECTIVE: The objective of this study was to compare the efficacy of ACBT with
      Acapella as methods of airway clearance in adults with stable, productive
      bronchiectasis. METHODS: Twenty patients (7 males), age 58 +/- 11 years (mean +/-
      SD), FEV1 64 +/- 22% predicted with stable (change of not greater than FEV1 10%
      predicted during 3 months prior to study), productive (history of expectoration
      of half an egg cup sputum/day) bronchiectasis attended the respiratory clinic on
      3 days. Day 1: 40-min training session on ACBT and Acapella. Days 2 and 3: 30-min
      treatment session of either ACBT or Acapella. Treatment order was determined by a
      concealed randomization procedure. The following outcomes were measured before
      and after treatment spirometry, SpO2 and breathlessness by an independent
      assessor who was blinded to treatment order. Weight of sputum (during treatment
      plus 30 min after treatment), number of coughs and patient preference were also
      recorded. RESULTS: No significant differences were found at baseline indicating
      that patients were stable. No significant differences were found between weight
      of sputum expectorated with ACBT treatment and weight of sputum expectorated with
      Acapella treatment--mean difference 0.54 g (95% CI -0.39 to 1.46). A greater
      proportion of patients preferred Acapella (14/20). CONCLUSION: Acapella is as
      effective a method of airway clearance as ACBT and may offer a user-friendly
      alternative to ACBT for patients with bronchiectasis.

PMID- 15942292
TI  - Polymorphisms of B7 (CD80 and CD86) genes do not affect disease susceptibility to
      sarcoidosis.
AB  - BACKGROUND: B7 proteins (CD80, CD86) are costimulatory molecules expressed on
      antigen-presenting cells and are essential factors for T cell activation.
      OBJECTIVES: The aim of this study is to investigate the relationship of B7 gene
      polymorphisms either to disease susceptibility or to cell profile of
      bronchoalveolar lavage (BAL) fluid in Japanese sarcoidosis patients. METHODS:
      Gene polymorphisms located in CD80 promoter, CD80 exon 3 and exon 8 of CD86 were
      examined in 146 Japanese sarcoidosis patients and 157 healthy controls using
      single-strand conformation polymorphism and direct sequencing. The distribution
      of genotypes was compared between the two groups. BAL fluid cell profiles were
      compared for the various genotypes of the different polymorphisms for the 62
      patients who underwent BAL. RESULTS: There were no significant differences in the
      distribution of genotypes or allele frequencies for all polymorphisms between
      sarcoidosis and controls. There were no significant differences in BAL fluid cell
      profiles among the different genotype groups of the various polymorphisms
      studied. CONCLUSIONS: There was no relationship between the B7 gene polymorphisms
      studied and disease susceptibility or BAL fluid cell profiles in Japanese
      sarcoidosis patients.

PMID- 15942293
TI  - Surfactant protein A detection in primary pulmonary adenocarcinoma without
      bronchioloalveolar pattern.
AB  - BACKGROUND: Immunohistochemical studies in human lung carcinoma reported positive
      staining of tumor cells for surfactant protein A (SP-A), especially in peripheral
      airway cell carcinoma, which include bronchioloalveolar carcinoma and in some
      reports also papillary subtypes. OBJECTIVE: The purpose of this study was to
      determine the SP-A expression in tumor cells of lung adenocarcinoma without a
      bronchioloalveolar pattern, classified according to the WHO. METHODS: In total,
      169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24
      papillary and 4 mucinous) were examined by immunohistochemistry for SP-A
      expression. RESULTS: Twenty-five percent of acinar, 38% of papillary and 3% of
      solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction
      of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This
      study included the largest number of acinar adenocarcinomas and solid
      adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also
      primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP
      A. A positive staining of hyperplastic type II cells surrounding the tumors or
      entrapped in the tumor could clearly be differentiated from the SP-A-positive
      stain of tumor cells. CONCLUSION: These results support the theory that SP-A
      producing cells may generate not only bronchioloalveolar and papillary carcinoma,
      but also other subtypes of lung adenocarcinoma.

PMID- 15942294
TI  - Bronchiolitis obliterans organizing pneumonia. Clinical and roentgenological
      features in 26 cases.
AB  - BACKGROUND: Bronchiolitis obliterans organizing pneumonia (BOOP) may be
      classified as cryptogenic (idiopathic) and secondary. There are no clear clinical
      and radiological features distinguishing between idiopathic and secondary BOOP.
      OBJECTIVES: To analyze the etiologic factors, clinical and radiological features,
      diagnostic approach and response to therapy at onset and outcome in subjects with
      BOOP. METHODS: The medical files of Erciyes University Hospital from 1995 to 2003
      were retrospectively reviewed. Patients with biopsy-proven BOOP were selected for
      evaluation. The etiology and initial features of BOOP, treatment, resolution,
      relapse, and survival were obtained from medical records, and a follow-up patient
      questionnaire. RESULTS: We have diagnosed 26 cases (13 males /13 females) with
      BOOP syndrome (mean age 54 +/- 15 years, range 14-93). More than half the
      patients (58%) were classified as idiopathic BOOP. Patients presented with cough
      (92%), dyspnea (70%), pleuritic chest pain, hemoptysis and fever (50%). The
      biopsy specimens had been obtained by transbronchial and/or transthoracic lung
      biopsy in 18 cases (69%). At radiological evaluation, there were bilateral patchy
      alveolar and/or interstitial infiltrates in 16 patients (62%), and solitary
      pneumonic involvement in 10 patients (38%). Three patients recovered
      spontaneously, 5 remained cured after resection of the focal lesion.
      Corticosteroid therapy was given in 17 patients (65%). Apart from four patients
      who died (death was attributable to BOOP in only 1 patient) and three patients
      who relapsed, the prognosis was good in all patients. CONCLUSIONS: The etiology
      of BOOP is usually idiopathic. We observed that hemoptysis and pleuritic chest
      pain were a relatively frequent symptom in BOOP in the present series, in
      contrast to previous observations. The diversity of radiological and clinical
      presentations including hemotysis and pleuritic chest pain should prompt
      consideration of the diagnosis in patients with persisting pulmonary symptoms and
      radiological findings.

PMID- 15942295
TI  - Respiratory syncytial virus pneumonitis in immunocompromised adults: clinical
      features and outcome.
AB  - BACKGROUND: Though predominantly an infection of children, respiratory syncytial
      virus (RSV) also infects adults, particularly those with immune compromise.
      OBJECTIVES: To define the clinical spectrum and impact of RSV pneumonitis on
      hospitalized, immunocompromised adults. METHODS: Retrospective chart review.
      Clinical parameters including premorbid conditions, presentation, radiologic
      findings, treatment and outcome were examined in a consecutive patients series
      from an inpatient tertiary-care center. Eleven immunocompromised adults who had
      undergone bronchoalveolar lavage (BAL) between January 1987 and December 1996 and
      who had culture-verified RSV pneumonitis were evaluated. RESULTS: This series
      consisted primarily of patients undergoing chemotherapy or bone marrow
      transplantation for lymphoma or leukemia. Two were immunosuppressed due to high
      dose corticosteroids. A majority (91%) were admitted between November and May,
      with dyspnea and productive cough. In contrast to earlier studies, there was a
      paucity of upper respiratory infection symptoms (i.e. sinus congestion, sore
      throat) and a preponderance of lower respiratory physical exam findings (i.e.
      wheezing, bibasilar rales). Patients were typically hypoxemic and febrile prior
      to BAL. Eight demonstrated co-isolates of bacterial or fungi on BAL. The chest
      radiographs generally revealed diffuse patchy infiltrates, including alveolar
      opacities. Histology demonstrated diffuse alveolar damage, bronchiolitis with
      organizing pneumonia, and hyaline membrane formation. Over half required
      intubation, and 55% died. Although ribavirin therapy may be beneficial in some
      intubated patients, its overall efficacy cannot be established from this series.
      CONCLUSION: RSV is a serious cause of morbidity and mortality in
      immunocompromised adults. Further development and implementation of an effective
      vaccine and additional therapeutic interventions are needed.

PMID- 15942296
TI  - Prevalence of chronic obstructive pulmonary disease and rhinitis in northern
      Greece.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) constitutes one of the
      main factors responsible for morbidity and mortality worldwide. Rhinitis has a
      high prevalence, but its relationship to COPD has not been determined.
      OBJECTIVES: To estimate the prevalence of COPD and rhinitis in northern Greece
      and to examine their correlation. PATIENTS AND METHODS: Of a total of 8,151
      subjects (aged 21-80 years, from three regions of northern Greece) invited to
      participate in the study, 6,112 (75%) were included. The regions studied were:
      (a) Thessaloniki (1,733 study participants, 52.7 +/- 18.6 years old), an urban
      area with particulate air pollution frequently exceeding the acceptable limit,
      (b) Eordea (3,537 study participants, 51.4 +/- 15.5 years old), a typical
      industrial area with particulate air pollution with daily values exceeding the
      acceptable limit and (c) Grevena (842 study participants, 55.6 +/- 15.4 years
      old), a mountainous area without pollution. The study participants filled in the
      questionnaire on respiratory symptoms of the Committee on Environmental and
      Occupational Health of the Medical Research Council and underwent spirometry and
      rhinomanometry tests. RESULTS: The prevalence of COPD was 5.6% (8.2% in men and
      2.5% in women) and that of rhinitis 24.7% (27.4% in men and 21.4% in women). COPD
      and rhinitis are related to common predisposing factors (smoking, age and sex).
      Moreover, rhinitis is related to particulate air pollution levels. CONCLUSIONS:
      The prevalence of COPD and rhinitis in northern Greece does not differentiate
      from that found in other industrial countries. A functional relationship between
      upper and lower airways is speculated.

PMID- 15942297
TI  - Impact of obstructive sleep apnea on right ventricular global function: sleep
      apnea and myocardial performance index.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is characterized by repetitive upper
      airway obstructions during sleep, and it might cause cardiovascular complications
      such as heart failure, arrhythmias, myocardial infarction, systemic and pulmonary
      hypertension. OBJECTIVES: To determine right ventricular diameters and myocardial
      performance index (MPI) reflecting ventricular global function in uncomplicated
      OSA patients. METHODS: 49 subjects without hypertension, diabetes mellitus, or
      any cardiac or pulmonary disease referred for evaluation of OSA had overnight
      polysomnography and complete echocardiographic assessment. According to the apnea
      hypopnea index (AHI), subjects were divided into three groups: group 1: control
      subjects (AHI <5, n = 20), group 2: patients with mild OSA (AHI: 5-14, n = 11),
      and group 3: moderate-severe OSA (AHI > or = 15, n = 18). Right ventricular free
      wall diameter was measured by M mode, and right ventricular MPI was calculated as
      (isovolumic contraction time + isovolumic relaxation time)/pulmonary ejection
      time. RESULTS: There were no differences of age, body mass index, heart rates,
      systolic and diastolic blood pressures among the groups (p > 0.05). Right
      ventricular end-diastolic and end-systolic diameters were not statistically
      different between the groups, and were within normal limits. Also, right
      ventricular free wall diameter was not significantly different between the groups
      of control, mild OSA and moderate-severe OSA (6.7 +/- 0.9, 6.9 +/- 1.0, 7.1 +/-
      1.1 mm, p > 0.05). Right ventricular diastolic dysfunction was shown only in
      group 3 patients. Right ventricular MPI was statistically higher in group 3 (0.62
      +/- 0.18) than in group 2 patients (0.50 +/- 0.10), and group 1 patients (0.48 +/
      0.08, p < 0.001). CONCLUSIONS: It was suggested that patients with moderate
      severe OSA had a right ventricular global dysfunction, in addition to the
      presence of a diastolic dysfunction.

PMID- 15942298
TI  - Contraindications and safety of transbronchial lung biopsy via flexible
      bronchoscopy. A survey of pulmonologists and review of the literature.
AB  - BACKGROUND: Transbronchial lung biopsy (TBLB) via flexible bronchoscopy is a
      common procedure performed by pulmonologists. Limited scientific data exist
      concerning the risk of this procedure in patients with conditions that may
      adversely affect the rate of procedural complications. OBJECTIVES: To evaluate
      the current practice pattern and attitude of pulmonologists toward the
      performance of TBLB in the presence of high-risk conditions. METHODS: A survey
      was constructed and distributed at the American College of Chest Physicians
      annual meeting, held in Philadelphia, USA, in November of 2001. RESULTS: A total
      of 227 surveys were distributed with a return of 158 (69.6%). Anticoagulation
      medications are temporarily held prior to TBLB by the majority of our survey
      respondents (98.7% for intravenous heparin, 90.5% for warfarin, and 87.3% for low
      molecular-weight heparin). Medications with effect on platelet function are held
      by fewer pulmonologists. There is a wide variation in the pulmonologists'
      perception of the risk of performing TBLB when certain medical conditions
      coexist: pulmonary hypertension [absolute contraindication (AC), 28.7%; relative
      contraindication (RC) 58.6%], superior vena cava syndrome (AC 19.6%, RC 51%),
      mechanical ventilation (AC 17.8%, RC 58.6%) and lung cavity/abscess (AC 7%, RC
      44.9%). A significant percentage of pulmonologists (55%) do not regard an
      elevated serum creatinine at any level as AC to TBLB. Thirty-eight percent of the
      survey participants administer desmopressin prior to TBLB in uremic patients to
      prevent excessive bleeding. CONCLUSIONS: Prior to performing bronchoscopic TBLB,
      the majority of pulmonologists temporarily holds anticoagulation medications.
      However, there is a lack of agreement in relation to perceived contraindications
      and safety of TBLB.

PMID- 15942300
TI  - A mass in the right cardiophrenic angle.

PMID- 15942299
TI  - Penetration of clarithromycin in experimental pleural empyema model fluid.
AB  - BACKGROUND: The degree of penetration of clarithromycin into the pleural fluid
      has not been studied. OBJECTIVE: To determine the degree to which clarithromycin
      penetrates into empyemic pleural fluid using a new rabbit model of empyema.
      METHODS: An empyema was created via the intrapleural injection of 1 ml turpentine
      followed 24 h later by instillation of 5 ml (10(10)) Escherichia coli bacteria
      (ATCC 35218) into the pleural space of New Zealand white rabbits. After an
      empyema was verified by thoracentesis and pleural fluid analysis, clarithromycin
      30 mg/kg was administered intravenously. Antibiotic levels were determined on
      samples of pleural fluid and blood samples collected serially over 12 h.
      Antibiotic levels were estimated using HPLC. RESULTS: The antibiotic penetrated
      well into the empyemic pleural fluid (AUC(PF)/AUC(serum) ratio of 1.57). The time
      to equilibration between the pleural fluid and blood antibiotic levels was 8 h.
      The peak pleural fluid level (Cmax(PF) of 2.88 microg/ml) occurred 1 h (Tmax(PF)
      of 1 h) after infusion and decreased thereafter. The Cmax(serum) was 3.53
      microg/ml at 1 h after administration. CONCLUSION: The levels of clarithromycin
      in the pleural fluid after intravenous administration are inhibitory for most of
      the usual pathogens causing empyema. The degree of penetration of clarithromycin
      should be considered when macrolides are selected for the treatment of patients
      with empyema.

PMID- 15942301
TI  - The missing stent--the most improbable complication.

PMID- 15942302
TI  - Mycobacterium kansasii endobronchial ulcer in a nonimmunocompromised patient.
AB  - In this report we describe the case of an immunocompetent patient found to have
      an endobronchial, ulcerated lesion due to Mycobacterium kansasii. Predisposing
      factors could have been severe endobronchial stenosis of the main stem bronchi
      and distortion of the carina, due to healed endobronchial tuberculosis. Diagnosis
      was set through fiberoptic bronchoscopy and the patient responded well to
      treatment. Endobronchial non tuberculous mycobacterial infection should be
      considered in both HIV seropositive and seronegative patients, especially in
      endemic areas and in the proper clinical setting. Prompt recognition is important
      for the effective control and prevention of an unfavorable outcome in an
      otherwise easily treatable disease.

PMID- 15942303
TI  - Long-term management of extensive tracheal stenosis due to formic acid chemical
      burn.
AB  - We report on a 26-year-old woman who during early infancy (6 months) suffered
      from a chemical burn of the skin and upper airways due to spill of formic acid
      powder. Twenty years after the initial injury, she presented with dyspnea and
      stridor due to severe tracheal stenosis. Several interventional bronchoscopic
      manipulations were initiated: incision of the stenotic lesion with Nd:YAG laser
      and dilatation with a valvuloplasty balloon which enabled silicone stent
      placement which was subsequently kept in place for 3 years. Complications during
      the 4th year after stenting led to the successful replacement of this stent by
      two autoexpandable metallic stents covering the total length of the trachea from
      the subglottic area to the carina. In post-burn inhalation injuries, a complex
      inflammatory process may be active for many years after the initial insult. These
      injuries respond to prolonged tracheal stenting and a conservative approach is
      recommended.

PMID- 15942304
TI  - Molecular pathology of non-small-cell lung cancer.
AB  - The molecular basis of lung carcinogenesis must be understood more fully and
      exploited to enhance survival rates of patients suffering from lung cancer. In
      this review we will discuss the major molecular alterations that occur in lung
      cancer. Emphasis is placed on alterations that occur early during carcinogenesis
      since they might be relevant for future screening programs. Finally we will
      shortly review new approaches that are used to study the molecular pathology of
      lung cancer and how they can be applied in a clinical setting.

PMID- 15942305
TI  - Relative utility of 6-minute walk vs. incremental shuttle walk: does it depend
      upon functional status?

PMID- 15942307
TI  - When is a wound really healed?

PMID- 15942314
TI  - Identifying and managing venous dermatitis.

PMID- 15942315
TI  - Ulcerations in primary hyperoxaluria.

PMID- 15942316
TI  - CMS examines the usual care of chronic wounds.

PMID- 15942317
TI  - Randomized clinical trial comparing OASIS Wound Matrix to Regranex Gel for
      diabetic ulcers.
AB  - OBJECTIVE: To compare healing rates at 12 weeks for full-thickness diabetic foot
      ulcers treated with OASIS Wound Matrix, an acellular wound care product, versus
      Regranex Gel. DESIGN: Randomized, prospective, controlled multicenter trial at 9
      outpatient wound care clinics. SUBJECTS: A total of 73 patients with at least 1
      diabetic foot ulcer were entered into the trial and completed the protocol.
      INTERVENTION: Patients were randomized to receive either OASIS Wound Matrix (n =
      37) or Regranex Gel (n = 36) and a secondary dressing. Wounds were cleansed and
      debrided, if needed, at a weekly clinic visit. Dressings were changed as needed.
      The maximum treatment period for each patient was 12 weeks. PRIMARY OUTCOME
      MEASURE: Incidence of healing in each group at 12 weeks. RESULTS: After 12 weeks
      of treatment, 18 (49%) OASIS-treated patients had complete wound closure compared
      with 10 (28%) Regranex-treated patients. CONCLUSION: Although the sample size was
      not large enough to demonstrate that the incidence of healing in the OASIS group
      was statistically superior (P = .055), the study results showed that treatment
      with OASIS is as effective as Regranex in healing full-thickness diabetic foot
      ulcers by 12 weeks.

PMID- 15942318
TI  - A survey of nurses' wound care knowledge.
AB  - PURPOSE: To provide information about nurses' knowledge and practices in the
      prevention and care of wounds, based on responses to a 2004 survey in Advances in
      Skin & Wound Care and its sister publication, Nursing2004. TARGET AUDIENCE: This
      continuing education activity is intended for physicians and nurses with an
      interest in understanding best practices for preventing and treating wounds.
      LEARNING OBJECTIVES: After reading the preceding article and taking this test,
      the participant should be able to: 1. Discuss the Advances in Skin & Wound Care
      and Nursing2004 wound care survey results. 2. Relate the survey responses to best
      practice standards for for preventing and treating wounds. 3. Identify
      implications for improvements in wound care education and practice based on
      survey results.

PMID- 15942320
TI  - More culturally sensitive neuropsychological tests (and normative data) needed.

PMID- 15942322
TI  - Complement activation in very early Alzheimer disease.
AB  - The activation of the classical complement (C)-system in early-stage Alzheimer
      disease (AD) and nondemented aging was examined with immunohistochemistry in
      subjects assessed by the Clinical Dementia Rating (CDR). Activation (staining for
      C3 and C4 fragments) was found in all brains with amyloid deposits, including all
      nondemented (CDR 0) cases, with either small numbers of diffuse plaques or with
      sufficient plaques and tangles to indicate preclinical AD. Staining for C3 and C4
      increased in parallel with plaque density in very mild to severe clinical AD. A
      subset of very mild AD (CDR 0.5) cases also showed C1q (on plaques) and C5b-9 (on
      neuritic plaques and tangles), whereas these C-fragments were consistently found
      in severe AD (CDR 3). Mirror section (split-face) analysis showed that C1q, C3,
      and apoJ (clusterin) occurred on the same plaques. However, C-system regulators
      CD59, CR1, DAF, and MCP were not detected on plaques or tangles at any stage,
      indicating that C-activation related to AD is incompletely controlled.

PMID- 15942323
TI  - Evaluation of selection bias in an incident-based dementia autopsy case series.
AB  - Neuropathological (np) relative frequency estimates of dementia may be biased if
      the autopsied subjects are not representative of all dementia subjects within a
      target population. We identified characteristics that differed between autopsied
      and non-autopsied subjects from an incident-based dementia case series and
      compared autopsy-based estimates of the relative frequency of np diagnoses before
      and after adjusting for potential selection bias. Clinically demented subjects
      who were autopsied (n = 206), had died but were not autopsied (n = 271), were
      still alive (n = 71), or had dropped out of the study (n = 82) were included.
      Compared with non-autopsied subjects, autopsied subjects were more likely to be
      Caucasian, educated beyond high school, and married. They also tended to have a
      lower baseline Mini-Mental State Examination score and were more likely to have a
      clinical diagnosis of Alzheimer disease (AD) than non-autopsied subjects.
      Neuropathological AD with Lewy bodies (LB) had the largest crude relative
      frequency estimate at 38% of the autopsy sample, followed by 25% for AD with
      vascular lesions, 13% for pure AD, 13% for LB (with or without vascular lesions),
      and 8% for pure vascular pathologies. Adjustment for potential sources of
      selection bias had little effect on relative frequency estimates, suggesting that
      np diagnoses in the autopsied subjects provide reasonable dementia relative
      frequency estimates among all clinically demented cases in this series.

PMID- 15942324
TI  - Performance of elderly Native Americans and Caucasians on the CERAD
      Neuropsychological Battery.
AB  - The performance of 40 elderly Native Americans and 40 demographically similar
      Caucasians clinically diagnosed with Alzheimer disease were compared on the
      Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological
      Battery (CERAD-NB). The purpose was to determine whether performance on the CERAD
      NB, a cognitive screening battery used to evaluate dementia in the elderly, is
      affected by cultural differences between these two groups, after controlling for
      age, education, and gender. All subjects were administered the CERAD-NB as part
      of a standard diagnostic evaluation. Statistical analyses revealed no significant
      differences between the two groups on any measures from the CERAD-NB. Thus, the
      CERAD-NB appears to be an efficient cognitive screening assessment in English
      speaking Native Americans with known or suspected dementing illness and it
      appears that special norms may not be necessary in this population. However,
      additional studies of larger samples are needed for confirmation and to explore
      factors such as education, acculturation, and degree of Native American heritage,
      which may influence cognitive test performance.

PMID- 15942325
TI  - Using the telephone to call for help and caregiver awareness in Alzheimer
      disease.
AB  - We assessed the ability of 73 patients with Alzheimer disease (AD) and mild
      cognitive impairment (MCI) from our outpatient clinic to demonstrate how they
      would use the telephone to call for help in case of an emergency. We also
      assessed their caregivers' awareness of their abilities. Overall, 44% of the
      patients did not demonstrate how to call for help correctly if they had no
      written telephone number to call, and 18% did not when they had a written number.
      There was an association between the abilities of the patients and their Mini
      Mental State Examination (MMSE) scores, with the patients with the lowest scores
      having the most difficulty (P < 0.0001). Surprisingly, 21% of those with MMSE
      scores 26-30 did not use the telephone correctly when they had no written number.
      Of the caregivers, 31% were incorrect in predicting their patients' abilities for
      the first task, and 11% were incorrect in predicting the second task. We conclude
      that AD patients lose their ability to use the telephone to call for help as
      their illness progresses. Furthermore, many caregivers are unaware of their
      patients' impairment. These findings highlight safety concerns in AD and suggest
      that caregivers could benefit from education about potential patient losses.

PMID- 15942326
TI  - Cognitive impairment and quality-of-life: views of providers of long-term care
      services.
AB  - Quality-of-life (QoL) is now recognized as a principal outcome marker for long
      term care. However, QoL is difficult to define and measure, especially in
      residents with dementia. Providers of long-term care services (n = 182) were
      asked to rate the importance of 19 psychosocial quality-of-life elements for
      hypothetical residents with physical impairment and for residents with cognitive
      impairment. Respondents also were asked to rate their ability to influence these
      elements for each type of resident. Respondents rated the importance of 18 of the
      19 elements and their ability to influence 17 of 19 elements lower for residents
      with cognitive impairment. Of the five types of respondents, certified nursing
      assistants (CNAs) rated their ability to influence these QoL elements the highest
      for both types of residents; physicians' ratings were the lowest. Pain management
      was given high ratings for both importance and ability to influence for both
      resident types; the lowest ratings were given for elements that pertained to
      residents' understanding. A strong correlation between ratings for importance and
      ability to influence was observed. Additional research is needed on the
      psychosocial aspects of long-term care residents' QoL, especially those with
      cognitive impairment.

PMID- 15942327
TI  - Association between dementia and infectious disease: evidence from a case-control
      study.
AB  - Inflammation plays a part in the etiology of dementia. Whether this is the
      primary pathogenesis, or a secondary reaction is unclear. We postulate that since
      systemic infection can provoke the enhanced synthesis of inflammatory mediators
      in the brain, such diseases may promote the onset of dementia. We carried out a
      nested case-control study using the General Practice Research Database. Cases
      were patients with incident dementia, and controls without such a diagnosis.
      Infectious episodes in the four years preceding diagnosis were counted using
      diagnostic codes, or prescription codes for anti-infective drugs. We considered
      age, sex, smoking, diabetes mellitus, and frequency of consultation as potential
      confounders. There were 9954 valid cases, and 9374 valid controls. Cases were on
      average older, more likely to be female, to smoke and to have diabetes, than the
      controls. There was an increased risk of diagnosis of dementia in those patients
      older than 84 with infections (OR for 2 or more infections compared with 0 or 1 =
      1.4, 95% CI 1.2 to 1.7). Smoking and diabetes mellitus were also shown to
      markedly increase the risk of diagnosis of dementia. We have shown a positive
      association between episodes of infection and increased likelihood of diagnosis
      of dementia in the very elderly. Smoking and diabetes mellitus are associated
      with onset of dementia in the elderly. The evidence from this study may represent
      cause and effect, since there is a credible biologic explanation.

PMID- 15942328
TI  - Gender differences in Alzheimer disease: the role of luteinizing hormone in
      disease pathogenesis.
AB  - Epidemiological data reporting the predisposition of women to Alzheimer disease
      has provided researchers with an important clue as to the identity of the driving
      pathogenic force and lead many to question the potential role of sex steroids,
      namely estrogen, in disease pathogenesis. However, while estrogen has become the
      primary focus of research in the field, inconclusive data regarding estrogen
      replacement therapy has lead some researchers to begin investigating the effects
      of the other hormones of the hypothalamic-pituitary-gonadal (HPG) axis on the
      aging brain. Certain hormones of the HPG axis, namely the gonadotropins
      (luteinizing hormone and follicle-stimulating hormone), are not only involved in
      regulating reproductive function via a complex feedback loop but are also known
      to cross the blood-brain barrier. Recently, we proposed that an increase in
      gonadotropin concentrations, not the decrease in steroid hormone (eg, estrogen)
      production following menopause/andropause, is a potentially primary causative
      factor for the development of Alzheimer disease. In this review, we examine how
      the gonadotropins may play a central and determining role in modulating the
      susceptibility to, and progression of, Alzheimer disease. Based on this, we
      suggest that therapeutic interventions targeted at gonadotropins may both prevent
      disease in those patients currently asymptomatic or may halt, and even reverse,
      disease in those currently afflicted.

PMID- 15942329
TI  - Dementia update 2005.

PMID- 15942330
TI  - Clinical predictors of and mortality in acute respiratory distress syndrome:
      potential role of red cell transfusion.
AB  - OBJECTIVE: Clinical predictors for acute respiratory distress syndrome (ARDS)
      have been studied in few prospective studies. Although transfusions are common in
      the intensive care unit, the role of submassive transfusion in non-trauma-related
      ARDS has not been studied. We describe here the clinical predictors of ARDS risk
      and mortality including the role of red cell transfusion. DESIGN: Observational
      prospective cohort. SETTING: Intensive care unit of Massachusetts General
      Hospital. PATIENTS: We studied 688 patients with sepsis, trauma, aspiration, and
      hypertransfusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred
      twenty-one (32%) subjects developed ARDS with a 60-day mortality rate of 46%.
      Significant predictors for ARDS on multivariate analyses included trauma
      (adjusted odds ratio [ORadj] 0.22, 95% confidence interval [CI] 0.09-0.53),
      diabetes (ORadj 0.58, 95% CI 0.36-0.92), direct pulmonary injury (ORadj 3.78, 95%
      CI 2.45-5.81), hematologic failure (ORadj 1.84, 95% CI 1.05-3.21), transfer from
      another hospital (ORadj 2.08, 95% CI 1.33-3.25), respiratory rate >33 breaths/min
      (ORadj 2.39, 95% CI 1.51-3.78), hematocrit >37.5% (ORadj 1.77, 95% CI 1.14-2.77),
      arterial pH <7.33 (ORadj 2.00, 95% CI 1.31-3.05), and albumin </=2.3 g/dL (ORadj
      1.80, 95% CI 1.18-2.73). Packed red blood cell transfusion was associated with
      ARDS (ORadj 1.52, 95% CI 1.00-2.31, p = .05). Significant predictors for
      mortality in ARDS included age (ORadj 1.96, 95% CI 1.50-2.53), Acute Physiology
      and Chronic Health Evaluation III score (ORadj 1.78, 95% CI 1.16-2.73), trauma
      (ORadj 0.075, 95% CI 0.006-0.96), corticosteroids before ARDS (ORadj 4.65, 95% CI
      1.47-14.7), and arterial pH <7.22 (ORadj 2.32, 95% CI 1.02-5.25). Packed red
      blood cell transfusions were associated with increased mortality in ARDS (ORadj
      1.10 per unit transfused; 95% CI 1.04-1.17) with a significant dose-dependent
      response (p = .02). CONCLUSIONS: Important predictors for the development of and
      mortality in ARDS were identified. Packed red blood cell transfusion was
      associated with an increased development of and increased mortality in ARDS.

PMID- 15942331
TI  - Large-scale implementation of sedation and delirium monitoring in the intensive
      care unit: a report from two medical centers.
AB  - OBJECTIVE: To implement sedation and delirium monitoring via a process
      improvement project in accordance with Society of Critical Care Medicine
      guidelines and to evaluate the challenges of modifying intensive care unit (ICU)
      organizational practice styles. DESIGN: Prospective observational cohort study.
      SETTING: The medical ICUs at two institutions: the Vanderbilt University Medical
      Center (VUMC) and a community Veterans Affairs hospital (York-VA). SUBJECTS:
      Seven hundred eleven patients admitted to the medical ICUs for >24 hrs and
      followed over 4,163 days during a 21-month study period. INTERVENTIONS: Unit-wide
      nursing documentation was changed to accommodate a sedation scale (Richmond
      Agitation-Sedation Scale) and delirium instrument (Confusion Assessment Method
      for the ICU). A 20-min introductory in-service was performed for all ICU nurses,
      followed by graded, staged educational interventions at regular intervals. Data
      were collected daily for compliance, and randomly 40% of nurses each day were
      chosen for accuracy spot-checks by reference raters. An implementation survey
      questionnaire was distributed at 6 months. MEASUREMENTS AND MAIN RESULTS: The
      implementation project involved 64 nurses (40 at VUMC and 24 at York-VA).
      Sedation and delirium monitoring data were recorded for 711 patients (614 at VUMC
      and 97 at York-VA). Compliance with the Richmond Agitation-Sedation Scale was
      94.4% (21,931 of 23,220) at VUMC and 99.7% (5,387 of 5,403) at York-VA.
      Compliance with the Confusion Assessment Method for the ICU was 90% (7,323 of
      8,166) at VUMC and 84% (1,571 of 1,871) at York-VA. The Confusion Assessment
      Method for the ICU was performed more often than requested on 63% of shifts
      (5,146 of 8,166) at VUMC and on 8% (151 of 1871) of shifts at York-VA. Overall
      weighted-kappa between bedside nurses and references raters for the Richmond
      Agitation-Sedation Scale were 0.89 (95% confidence interval, 0.88 to 0.92) at
      VUMC and 0.77 (95% confidence interval, 0.72 to 0.83) at York-VA. Overall
      agreement (kappa) between bedside nurses and reference raters using the Confusion
      Assessment Method for the ICU was 0.92 (95% confidence interval, 0.90-0.94) at
      VUMC and 0.75 (95% confidence interval, 0.68-0.81) at York-VA. The two most-often
      cited barriers to implementation were physician buy-in and time. CONCLUSIONS:
      With minimal training, the compliance of bedside nurses using sedation and
      delirium instruments was excellent. Agreement of data from bedside nurses and a
      reference-standard rater was very high for both the sedation scale and the
      delirium assessment over the duration of this process-improvement project.

PMID- 15942332
TI  - Glutamine attenuates lung injury and improves survival after sepsis: role of
      enhanced heat shock protein expression.
AB  - OBJECTIVE: Heat shock protein (HSP) expression is vital to cellular and tissue
      protection after stress or injury. However, application of this powerful tool in
      human disease has been limited, as known enhancers of HSPs are toxic and not
      clinically relevant. Glutamine (GLN) can enhance HSP expression in non-clinically
      relevant animal injury models. The aim of this study was to assess the ability of
      GLN to enhance pulmonary HSP expression, attenuate lung injury, and improve
      survival after sepsis in the rat. DESIGN: Prospective, randomized, controlled
      animal trial. SETTING: University research laboratory. SUBJECTS: Male Sprague
      Dawley rats. INTERVENTIONS: We utilized a rat model of cecal ligation and
      puncture to induce sepsis. GLN or saline was administered 1 hr after initiation
      of sepsis via single tail-vein injection. We analyzed heat shock factor-1
      phosphorylation, HSP-70, and HSP-25 via Western blot. Tissue metabolism was
      assayed by magnetic resonance spectroscopy. Occurrence of lung injury was
      determined via histopathologic examination. An inhibitor of HSP expression,
      quercetin, was utilized to assess role of HSP expression in prevention of sepsis
      related mortality. MEASUREMENTS AND MAIN RESULTS: GLN, given after initiation of
      sepsis, enhanced pulmonary heat shock factor-1 phosphorylation, HSP-70, HSP-25,
      and attenuated lung injury after sepsis. Further, GLN improved indices of lung
      tissue metabolic function (adenosine 5-triphosphate/adenosine 5-diphosphate
      ratio, nicotinamide adenine dinucleotide) after sepsis. No significant effect of
      GLN on lung tissue-reduced glutathione was observed. GLN treatment led to a
      significant decrease in mortality (33% [6 of 18] GLN-treated rats vs. 78% [14 of
      17] saline-treated rats). Administration of the HSP inhibitor quercetin blocked
      GLN-mediated enhancement of HSP expression and abrogated GLN's survival benefit.
      CONCLUSIONS: GLN has been safely administered to critically ill patients and
      shown to improve outcome without clear understanding of the protective mechanism.
      Our results indicate GLN may prevent the occurrence of lung injury, lung tissue
      metabolic dysfunction, and mortality after sepsis via enhancement of deficient
      lung heat shock factor-1 phosphorylation/activation and HSP expression.

PMID- 15942333
TI  - Glucocorticoid therapy in neurologic critical care.
AB  - BACKGROUND: The pivotal role of inflammation and edema across the spectrum of
      central nervous system injury has driven extensive investigation into the
      therapeutic potential of glucocorticoids. OBJECTIVE: To review the experimental
      and clinical data relating to the efficacy and adverse effects of glucocorticoids
      in conditions encountered in critical neurologic and neurosurgical illness. DATA
      SOURCE: Search of MEDLINE and Cochrane databases, manual review of article
      bibliographies. DATA SYNTHESIS AND CONCLUSIONS: The efficacy of glucocorticoids
      is well established in ameliorating edema associated with brain tumors and in
      improving outcome in subsets of patients with bacterial meningitis. Despite
      frequently encouraging experimental results, clinical trials of glucocorticoids
      in ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage,
      and traumatic brain injury have not shown a definite therapeutic effect. The
      evidence supporting glucocorticoid therapy for spinal cord injury is
      controversial; however methylprednisolone continues to be widely employed in this
      setting.

PMID- 15942334
TI  - Give your patient a fast hug (at least) once a day.
AB  - OBJECTIVE: To introduce the Fast Hug mnemonic (Feeding, Analgesia, Sedation,
      Thromboembolic prophylaxis, Head-of-bed elevation, stress Ulcer prevention, and
      Glucose control) as a means of identifying and checking some of the key aspects
      in the general care of all critically ill patients. DESIGN: Not applicable.
      SETTING: Any intensive care unit at any time. PATIENTS: All intensive care unit
      patients. INTERVENTIONS: Dependent on the results of applying the Fast Hug.
      MEASUREMENTS AND MAIN RESULTS: Not applicable. CONCLUSIONS: Application of this
      simple strategy encourages teamwork and may help improve the quality of care
      received by our intensive care unit patients.

PMID- 15942336
TI  - Ultrasound diagnosis of occult pneumothorax.
AB  - OBJECTIVES: Pneumothorax can be missed by bedside radiography, and computed
      tomography is the current alternative. We asked whether lung ultrasound could be
      of any help in this situation. DESIGN: Retrospective study. SETTING: The medical
      intensive care unit of a university-affiliated teaching hospital. PATIENTS: All
      patients admitted to the intensive care unit are routinely scanned with whole
      body ultrasound (including screening for pneumothorax) and chest radiography. The
      study population included 200 consecutive undifferentiated intensive care unit
      patients who received a chest computed tomography scan in addition to ultrasound
      and chest radiograph. Forty-seven consecutive cases of radioccult pneumothorax
      were compared with 310 consecutive hemithoraces free from pneumothorax in the
      intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Three signs
      were investigated at the anterolateral chest wall in supine patients: lung
      sliding, the A line sign, and the lung point. A total of 357 hemithoraces were
      analyzed in this study, 47 with occult pneumothorax and 310 controls. Four of the
      47 cases of pneumothorax were excluded from the final analysis (parietal
      emphysema) as well as eight of the 310 controls (large dressings), leaving a
      final study population of 345 hemithoraces in 197 patients. Feasibility was 98%.
      Ultrasound scans in all 43 examinable patients with pneumothorax showed absent
      lung sliding, 41 of 43 patients had the A line sign, and 34 exhibited a lung
      point. Among 302 analyzable controls, 65 had absent lung sliding, 16 of them
      showed an A line sign, and none showed a lung point. For the diagnosis of occult
      pneumothorax, the abolition of lung sliding alone had a sensitivity of 100% and a
      specificity of 78%. Absent lung sliding plus the A line sign had a sensitivity of
      95% and a specificity of 94%. The lung point had a sensitivity of 79% and a
      specificity of 100%. CONCLUSIONS: For the diagnosis of occult pneumothorax,
      ultrasound can decrease the need for computed tomography.

PMID- 15942337
TI  - Prognostic factors in victims of falls from height.
AB  - OBJECTIVE: Falls from height cause significant mortality in the urban
      environment, but reliable prognostic factors have not been identified. Even the
      intuitive relation between the distance fallen and mortality rate has been
      questioned. Our objective was to determine factors predictive of increased
      mortality rate in victims of falls from height. DESIGN: Clinical observational
      study, retrospective for January 1998 to May 1999 and prospective from June 1999
      to September 2000. SETTING: The study population was drawn from Seine-Saint
      Denis, an urban region near Paris with 1.3 million inhabitants treated by a
      French out-of-hospital medical emergencies unit. PATIENTS: Patients were victims
      of falls from height >3 m, age >12 yrs. Study entry was performed on the scene by
      an emergency physician from the medical emergencies unit. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Studied data included age, gender, circumstances
      of fall, height of fall, nature of the impact surface (soft or hard), transient
      impact preceding final impact, and part of the body touching the ground first.
      The primary end point was mortality. The study included 287 patients, 116 (40%)
      during the retrospective phase and 171 (60%) during the prospective phase. Ninety
      seven patients (34%) ultimately died. In multivariate analysis, age (mean, 41.6
      +/- 16.6 yrs in patients who died vs. 34.9 +/- 14.9 in survivors; odds ratio,
      1.05; p < .0005); height of fall (median, 5.0; 3.8-8.0 vs. 2.0; 1.2-3.0 floors;
      odds ratio, 1.24; p < .0001); nature of the impact surface (hard in 39% vs. soft
      in 22%; odds ratio, 2.7; p < .05); and head, anterior, and lateral body surfaces
      touching the ground first (with respectively mortality rates of 44%, odds ratio,
      16.7, p = .0001; 57%, odds ratio, 10.6, p < 0.005; 32%, odds ratio, 11.1, p <
      .001) were independently correlated with the final mortality rate. CONCLUSIONS:
      Patient age, height of fall, impact surface nature, and body part first touching
      the ground are independent prognostic factors in victims of falls from height.

PMID- 15942338
TI  - Factors influencing the estimation of extravascular lung water by transpulmonary
      thermodilution in critically ill patients.
AB  - OBJECTIVE: To investigate factors that may influence the estimation of
      extravascular lung water (EVLW) with a single (cold) indicator compared with
      assessment using two indicators (thermo-dye dilution). DESIGN: Post hoc analysis
      of an electronic hemodynamic database. SETTING: Surgical intensive care unit of a
      university hospital. PATIENTS: Forty-eight critically ill patients monitored by
      the thermo-dye dilution technique in the postoperative period. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: The EVLW was simultaneously assessed by the
      thermo-dye dilution technique (EVLWref) and estimated by transpulmonary
      thermodilution (EVLWest). EVLWref index ranged between 1 and 40 mL/kg (mean 10 +/
      7 mL/kg) and EVLWest between 2 and 39 mL/kg (mean 9 +/- 6 mL/kg). EVLWref was
      closely correlated (r = .96) with EVLWest. The mean difference (bias) between
      EVLWref and EVLWest was -0.5 +/- 1.9 mL/kg. The bias was not influenced by the
      weight, height, body surface area, body mass index, Pao2, intrathoracic blood
      volume, cardiac output, or dosage of vasoactive agents. In contrast, the bias was
      slightly but significantly influenced by EVLWref, Pao2/Fio2 ratio, tidal volume,
      and level of positive end-expiratory pressure. CONCLUSIONS: In our surgical
      intensive care unit population, the estimation of EVLW by transpulmonary
      thermodilution was influenced by the amount of EVLW, the Pao2/Fio2 ratio, the
      tidal volume, and the level of positive end-expiratory pressure. However,
      compared with the double indicator method, transpulmonary thermodilution
      estimation remained clinically acceptable even in patients with severe lung
      disease.

PMID- 15942339
TI  - Clinical resolution in patients with suspicion of ventilator-associated
      pneumonia: a cohort study comparing patients with and without acute respiratory
      distress syndrome.
AB  - OBJECTIVES: To determine the pattern of resolution of classic infectious and
      respiratory variables in patients with ventilator-associated pneumonia (VAP) and
      appropriate empirical therapy, depending on the presence of acute respiratory
      distress syndrome (ARDS). A secondary objective was to identify clinical
      variables that might be useful for monitoring response to therapy. DESIGN:
      Prospective, observational cohort study. SETTING: Medical-surgical intensive care
      unit. PATIENTS: Seventy-five episodes of VAP without ARDS were identified and
      compared with 20 episodes with ARDS at VAP onset. Six episodes were excluded due
      to in vitro resistance to the initial antibiotic choice and six due to death in
      the first 72 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resolution
      of fever, Pao2/Fio2 >250 mm Hg, and white blood cell count in episodes of VAP
      were present in 73.3%, 74.7%, and 53.3% of patients after 3 days of therapy.
      Indeed, >50% of episodes with the absence of ARDS presented resolution of fever
      and Pao2/Fio2 >250 within the first day of therapy. In contrast, resolution of
      radiologic opacities and clearance of secretions (median of 14 and 6 days of
      resolution) were late events. In patients with ARDS, resolution of fever remained
      the earliest variable. However, similar to Pao2/Fio2 250 and white blood cell
      count, fever showed a significantly worse pattern after 3 days of therapy: 45%,
      15% and 25%, respectively. Radiologic resolution was an extremely poor indicator,
      being present in only 10% of ARDS patients after 15 days of follow-up. Failure to
      improve after 48 hrs of therapy was documented in 65% of ARDS patients and 14.7%
      of controls (p < .05). CONCLUSIONS: Measures of oxygenation and core temperature
      can help physicians to individualize and shorten the duration of antibiotic
      therapy in VAP episodes. ARDS patients with VAP take twice as long to resolve
      fever, whereas hypoxemia should be ignored in defining resolution in this subset.

PMID- 15942340
TI  - The hepatoadrenal syndrome: a common yet unrecognized clinical condition.
AB  - OBJECTIVE: Adrenal failure is common in critically ill patients, particularly
      those with sepsis. As liver failure and sepsis are both associated with increased
      circulating levels of endotoxin and proinflammatory mediators and reduced levels
      of apoprotein-1/high-density lipoprotein, we postulated that adrenal failure may
      be common in patients with liver disease. DESIGN: Clinical study. SETTING: Liver
      transplant intensive care unit. PATIENTS: The study cohort included 340 patients
      with liver disease. INTERVENTIONS: Based on preliminary observational data, all
      patients admitted to our 28-bed liver transplant intensive care unit (LTICU)
      undergo adrenal function testing. An honest broker system was used to extract
      clinical, hemodynamic, medication, and laboratory data on patients admitted to
      the LTICU from March 2002 to March 2004. A random (stress) cortisol level <20
      microg/dL in a highly stressed patient (respiratory failure, hypotension) was
      used to diagnose adrenal insufficiency. In all other patients, a random cortisol
      level <15 microg/dL or a 30-min level <20 microg/dL post-low-dose (1 microg)
      cosyntropin was considered diagnostic of adrenal insufficiency. Patients were
      grouped as follows: a) chronic liver failure; b) fulminant hepatic failure; c)
      patients immediately status post-orthotopic liver transplantation receiving a
      steroid-free protocol of immunosuppression; and d) patients status post-remote
      liver transplant (>/=6 months). The decision to treat patients with stress doses
      of hydrocortisone was at the discretion of the treating intensivist and
      transplant surgeon. MEASUREMENTS AND MAIN RESULTS: Two-hundred and forty-five
      (72%) patients met our criteria for adrenal insufficiency (the hepatoadrenal
      syndrome). Eight (33%) patients with fulminant hepatic failure, 97 (66%) patients
      with chronic liver disease, 31(61%) patients with a remote history of liver
      transplantation, and 109 (92%) patients who had undergone liver transplantation
      under steroid-free immunosuppression were diagnosed with adrenal insufficiency.
      The high-density lipoprotein level at the time of adrenal testing was the only
      variable predictive of adrenal insufficiency (p < .0001). In vasopressor
      dependent patients with adrenal insufficiency, treatment with hydrocortisone was
      associated with a significant reduction (p = .02) in the dose of norepinephrine
      at 24 hrs, whereas the dose of norepinephrine was significantly higher (p = .04)
      in those patients with adrenal failure not treated with hydrocortisone. In
      vasopressor-dependent patients without adrenal insufficiency, treatment with
      hydrocortisone did not affect vasopressor dose at 24 hrs. One hundred and forty
      one patients (26.4%) died during their hospitalization. The baseline serum
      cortisol was 18.8 +/- 16.2 microg/dL in the nonsurvivors compared with 13.0 +/-
      11.8 microg/dL in the survivors (p < .001). Of those patients with adrenal
      failure who were treated with glucocorticoids, the mortality rate was 26%
      compared with 46% (p = .002) in those who were not treated. In those patients
      receiving vasopressor agents at the time of adrenal testing, the baseline
      cortisol was 10.0 +/- 4.8 microg/dL in those with adrenal insufficiency compared
      with 35.6 +/- 21.2 microg/dL in those with normal adrenal function. Vasopressor
      dependent patients who did not have adrenal failure had a mortality rate of 75%.
      CONCLUSIONS: Patients with liver failure and patients post-liver transplantation
      have an exceedingly high incidence of adrenal failure, which may be
      pathophysiologically related to low levels of high-density lipoprotein. Treatment
      of patients with adrenal failure may improve outcome. High baseline serum
      cortisol levels may be a maker of disease severity and portend a poor prognosis.

PMID- 15942341
TI  - Delirium as detected by the CAM-ICU predicts restraint use among mechanically
      ventilated medical patients.
AB  - OBJECTIVE: The first goal of this investigation was to identify individuals with
      delirium defined by the Confusion Assessment Method for the Intensive Care Unit
      (CAM-ICU) among medical patients with respiratory failure. Our second goal was to
      compare clinical interventions including use of continuous sedation infusions,
      the number of ventilator-free days, ICU length of stay, hospital mortality, and
      use of physical restraints in mechanically ventilated patients with and without
      delirium. DESIGN: A prospective, single-center, observational cohort study.
      SETTING: The medical intensive care unit (19 beds) of an urban teaching hospital.
      PATIENTS: Adult, intubated, and mechanically ventilated patients. INTERVENTIONS:
      Daily evaluation with the CAM-ICU, outcomes assessment, and prospective data
      collection. MEASUREMENTS AND MAIN RESULTS: Among 93 patients evaluated using the
      CAM-ICU, 44 patients (47%) developed delirium (CAM-ICU+) for >/=1 day while in
      the intensive care unit. Twenty-two patients (24%) had no episodes of delirium
      recorded (CAM-ICU-), and 27 (29%) remained comatose until extubation or death. A
      statistically greater number of patients with delirium (CAM-ICU+) received
      continuous infusions of midazolam (59% vs. 32%, p < .05) or fentanyl (57% vs.
      32%, p < .05) and physical soft-limb restraints (77% vs. 50%, p < .05) compared
      with patients without delirium (CAM-ICU-). CONCLUSIONS: The identification of
      delirium using the CAM-ICU was associated with greater use of continuous sedation
      infusions and physical restraints. Additional studies are required to determine
      how the use of these specific interventions influences the occurrence and the
      natural history of delirium among critically ill patients.

PMID- 15942342
TI  - Daily cost of an intensive care unit day: the contribution of mechanical
      ventilation.
AB  - OBJECTIVE: To quantify the mean daily cost of intensive care, identify key
      factors associated with increased cost, and determine the incremental cost of
      mechanical ventilation during a day in the intensive care unit. DESIGN:
      Retrospective cohort analysis using data from NDCHealth's Hospital Patient Level
      Database. SETTING: A total of 253 geographically diverse U.S. hospitals.
      PATIENTS: The study included 51,009 patients >/=18 yrs of age admitted to an
      intensive care unit between October 1, 2002, and December 31, 2002.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Days of intensive care and
      mechanical ventilation were identified using billing data, and daily costs were
      calculated as the sum of daily charges multiplied by hospital-specific cost-to
      charge ratios. Cost data are presented as mean (+/-sd). Incremental daily cost of
      mechanical ventilation was calculated using log-linear regression, adjusting for
      patient and hospital characteristics. Approximately 36% of identified patients
      were mechanically ventilated at some point during their intensive care unit stay.
      Mechanically ventilated patients were older (63.5 yrs vs. 61.7 yrs, p < .0001)
      and more likely to be male (56.1% vs. 51.8%, p < 0.0001), compared with patients
      who were not mechanically ventilated, and required mechanical ventilation for a
      mean duration of 5.6 days +/- 9.6. Mean intensive care unit cost and length of
      stay were 31,574 +/- 42,570 dollars and 14.4 days +/- 15.8 for patients requiring
      mechanical ventilation and 12,931 +/- 20,569 dollars and 8.5 days +/- 10.5 for
      those not requiring mechanical ventilation. Daily costs were greatest on
      intensive care unit day 1 (mechanical ventilation, 10,794 dollars; no mechanical
      ventilation, 6,667 dollars), decreased on day 2 (mechanical ventilation:, 4,796
      dollars; no mechanical ventilation, 3,496 dollars), and became stable after day 3
      (mechanical ventilation, 3,968 dollars; no mechanical ventilation, 3,184
      dollars). Adjusting for patient and hospital characteristics, the mean
      incremental cost of mechanical ventilation in intensive care unit patients was
      1,522 dollars per day (p < .001). CONCLUSIONS: Intensive care unit costs are
      highest during the first 2 days of admission, stabilizing at a lower level
      thereafter. Mechanical ventilation is associated with significantly higher daily
      costs for patients receiving treatment in the intensive care unit throughout
      their entire intensive care unit stay. Interventions that result in reduced
      intensive care unit length of stay and/or duration of mechanical ventilation
      could lead to substantial reductions in total inpatient cost.

PMID- 15942343
TI  - Limitation and withdrawal of intensive therapy at the end of life: practices in
      intensive care units in Mumbai, India.
AB  - OBJECTIVE: To describe the practices in intensive care units in Mumbai hospitals
      regarding limitation and withdrawal of care at the end of life. DESIGN: Review of
      prospectively collected data. SETTINGS: Intensive care units of four major
      hospitals (two private tertiary referral general hospitals, one mixed public and
      private cancer referral hospital, and one large public hospital). PATIENTS:
      Hospital and intensive care unit patients who died during the study period.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured the percentage of
      hospital deaths occurring inside and outside intensive care units and the
      incidence of withholding intubation, withholding other therapy, and withdrawing
      therapy for deaths in the intensive care unit. The proportion of hospital deaths
      that occurred in an intensive care unit was 14% in the cancer hospital, 23% in
      the public hospital, and 58-73% in the two private hospitals (chi-square test for
      trends, p < .0001). Of the 143 deaths that occurred in intensive care unit,
      limitation of care occurred in 49 patients. Twenty-five percent of these patients
      were not intubated terminally, 67% were initially intubated and ventilated but
      failed to recover and subsequently had no further escalation of therapy, and 8%
      had withdrawal of therapy. Therapy was limited in 19% of deaths in the public
      hospital intensive care unit (odds ratio, 0.44; 95% confidence interval, 0.2
      0.97) vs. 40%, 41%, and 50% of deaths in the other three intensive care units.
      CONCLUSIONS: Therapy is limited in a significant proportion of intensive care
      unit patients. Significant differences in the practice of limitation of therapy
      exist between public and private hospitals. Lack of access to a limited number of
      intensive care unit beds, especially in the public hospital, may constitute
      implicit limitation of care.

PMID- 15942344
TI  - Prospective study of arterial and central venous catheter colonization and of
      arterial- and central venous catheter-related bacteremia in intensive care units.
AB  - OBJECTIVE: To compare the rates of positive quantitative culture (PQC) of
      arterial catheter (AC) and central venous catheter (CVC) tips and of CVC- and AC
      related bacteremia in intensive care unit patients undergoing placement of both
      ACs and CVCs. DESIGN: Prospective, descriptive survey. To control for a
      difference in the severity of patients having an AC or CVC, only patients having
      both an AC and a CVC were included. SETTING: An adult, nine-bed medical/surgical
      intensive care unit at a university teaching hospital. SUBJECTS: The analysis
      included 308 CVCs and 299 ACs inserted in 212 severely ill patients, with a mean
      +/- sd Simplified Acute Physiology Score II of 52 +/- 22 and an intensive care
      unit mortality of 33% (69 of 212). INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The same insertion and maintenance procedures were used for both types
      of catheter. A PQC was defined by a catheter tip culture yielding >/=10(3) colony
      forming units/mL. Catheter-related bacteremia was defined by a PQC and a blood
      culture positive for the same microorganism. The cumulative incidence
      (PQCs/number of catheters inserted) was 9.4% (29/308) for CVCs and 7.7% (23/299)
      for ACs (p = .44). Incidence density (PQCs/1,000 catheter days) was 12.0 for CVCs
      versus 9.3 for ACs. At the femoral site, there was no significant difference
      between CVCs and ACs in the cumulative incidences and incidence densities of
      PQCs. Two instances of catheter-related bacteremia were observed, one involving a
      CVC and one involving an AC. CONCLUSIONS: Among severely ill patients with both
      CVCs and ACs, the epidemiology of PQCs of CVCs and ACs is comparable when the
      same infection control measures are used for the insertion and maintenance of
      both types of catheters.

PMID- 15942345
TI  - Myocardial ischemia, cardiac troponin, and long-term survival of high-cardiac
      risk critically ill intensive care unit patients.
AB  - OBJECTIVES: To determine the incidence and association of myocardial ischemia
      with troponin elevation and survival in high-cardiac-risk intensive care
      patients. DESIGN: Prospective observational study. SETTING: Intensive care unit
      of a tertiary hospital. SUBJECTS: One-hundred one general intensive care unit
      patients having a history of coronary artery disease or at least two risk factors
      for coronary artery disease. INTERVENTIONS: Continuous 12-lead
      electrocardiographic monitoring with on-line ST-trend analysis, daily cardiac
      troponin measurements, clinical and physiologic assessment, and up to 2-yr follow
      up for survival. MEASUREMENTS AND MAIN RESULTS: During 8,988 hrs or a mean +/- sd
      of 95 +/- 85 hrs/patient of continuous 12-lead electrocardiographic monitoring,
      21 patients (21%) had ischemic ST-segment changes, characterized in most (19) by
      ST depression and lasting >60 mins in 15 (71.4%). Of the 38 patients (38%) with
      troponin elevation, myocardial infarction was clinically suspected in four and
      myocardial ischemia on continuous 12-lead electrocardiographic monitoring was
      observed in 14 (36.8%). Fourteen (66.7%) of the patients with ischemic ST changes
      and 12 (75%) of those with prolonged (>60 mins) ischemia had troponin elevation.
      The sensitivity, specificity, and positive and negative predictive values of
      prolonged (>60 mins) ischemia predicting troponin elevation were 31.6%, 95.2%,
      80.0%, and 69.8%, respectively. Prolonged (>60 mins) ischemia was significantly
      associated with troponin elevation by both univariate and multivariate analyses
      (odds ratio = 9.0; p = .008). Acute Physiology and Chronic Health Evaluation II
      score, renal failure, and the use of norepinephrine also independently predicted
      troponin elevation. Troponin but not ischemia predicted increased 1-month, 6
      month, and 2-yr mortality (odds ratio = 6.0, 3.2, and 2.99, respectively; p <
      .001). CONCLUSIONS: Silent ischemia is strongly associated with troponin
      elevation in high-cardiac-risk intensive care unit patients, and troponin
      elevation predicts both early and late mortality.

PMID- 15942346
TI  - Diagnostic and predictive value of the silkworm larvae plasma test for
      postoperative infection following gastrointestinal surgery.
AB  - OBJECTIVE: To determine whether the silkworm larvae plasma (SLP) test is a
      reliable diagnostic marker of infection in patients with infectious complications
      following gastrointestinal surgery. DESIGN: Prospective study. SETTING:
      Department of Surgery, University Hospital, Shiga University of Medical Science.
      PATIENTS: One hundred and twelve adult patients undergoing gastrointestinal
      surgery INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-nine of 112
      patients developed infectious complications (infected group). Seven patients with
      sepsis (severely infected group) and 32 patients without sepsis (minor infected
      group) were observed. The operation time, blood loss, and age were significantly
      greater in both infected groups than in the noninfected group. The systemic
      inflammatory response syndrome score on postoperative day (POD) 1 and POD7 was
      highest in the severely infected group. The increase in C-reactive protein on
      POD3 and POD7 was significantly higher in both infected groups than in the
      noninfected group. White blood cell counts on POD7 were elevated significantly
      higher in the severely infected group than in the other groups. Immediately after
      surgery, SLP activity significantly increased compared with presurgery in all
      groups and was significantly higher in the minor and severely infected groups
      than in the noninfected group. The increased SLP activity returned to
      preoperative levels in the minor and noninfected groups; however, SLP activity in
      the severely infected groups remained high throughout the observational period.
      The most significant factor and time point that predicted infectious
      complications were the SLP test on POD1; sensitivity 66.7%, specificity 90.4%,
      positive and negative predictive values 78.8% and 83.5%. The area under the
      receiver operating characteristic curve for the SLP test was 0.813 +/- 0.046.
      CONCLUSIONS: The SLP test appears to be a useful marker of diagnosis and
      prediction of infectious complications following gastrointestinal surgery.
      Moreover, the SLP test may be able to evaluate not only the existence but also
      the severity of infection in surgical patients.

PMID- 15942347
TI  - Admission hypothermia and outcome after major trauma.
AB  - OBJECTIVE: Uncontrolled exposure hypothermia is believed to be deleterious in the
      setting of major trauma. Prevention of hypothermia in the injured patient is
      currently practiced in both prehospital and in-hospital settings. However, this
      standard is based on studies of limited patient series that were not designed to
      identify the independent relationship between hypothermia and mortality. Recent
      studies suggest that therapeutically applied hypothermia may benefit selected
      patient subsets. The goal of this study was to evaluate the independent
      association between admission hypothermia and mortality after major trauma, with
      adjustment for clinical confounders. DESIGN: Retrospective analysis of a
      statewide trauma registry. The primary outcome was death at hospital discharge.
      The key exposure was hypothermia, defined as body temperature </=35 degrees C at
      admission. Multivariate regression was used to risk-adjust for age, severity and
      mechanism of injury, and route of temperature measurement. Additional adjustment
      for prehospital exposure time and intravenous fluid therapy was also evaluated.
      SETTING: Trauma centers of the Commonwealth of Pennsylvania. PATIENTS: All trauma
      patients >/=16 yrs of age for the years 2000-2002. Transferred patients were
      excluded. Patients were excluded if temperature or route of temperature
      measurement was not known. Both the full cohort and a subset with isolated severe
      head injury were evaluated. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Of 38,520 patients, 1,921 (5.0%) were hypothermic at admission. Admission
      hypothermia was independently associated with increased odds of death in both the
      full cohort (odds ratio, 3.03; 95% confidence interval, 2.62-3.51) and the subset
      with isolated severe head injury (2.21; 1.62-3.03), with adjustment for age,
      severity and mechanism of injury, and route of temperature measurement.
      CONCLUSIONS: Admission hypothermia is independently associated with increased
      adjusted odds of death after major trauma. The increase in mortality is not
      completely attributable to physiologic presentation or injury pattern or
      severity.

PMID- 15942348
TI  - Sepsis up-regulates the expression of connexin 40 in rat aortic endothelium.
AB  - OBJECTIVE: A distinctive feature of sepsis is a pleiotropic modification of
      membrane protein expression in the vascular endothelium, associated with
      diminished endothelium-dependent relaxation (endothelial dysfunction). In
      cultured endothelial cells, inflammatory stimuli alter expression of connexins
      (Cx), proteins that make up the gap junctions responsible for intercellular
      communication. In the present study, we tested whether the polymicrobial sepsis
      induced by cecal ligation and perforation in the rat alters the expression of the
      connexins present in the vascular endothelium (i.e., Cx37, Cx40, and Cx43). We
      also examined a possible association between such changes and endothelial
      dysfunction in this model. DESIGN: Animal study, with two parallel groups.
      SETTING: Animal research facility. SUBJECTS: One hundred four male adult Wistar
      rats. INTERVENTIONS: Rats underwent either cecal ligation and perforation to
      induce sepsis or a sham operation and were killed after a variable time, mostly
      24 hrs. MEASUREMENTS AND MAIN RESULTS: Experiments designed to test for the
      impact of sepsis on connexin expression disclosed a three-fold increase in Cx40
      messenger RNA and protein in the aorta, an effect that peaked at 24 hrs after
      cecal ligation and perforation, was specific to this connexin (i.e., levels of
      Cx37 and Cx43 did not vary), and was restricted to the aortic endothelium.
      Experiments designed to test the permeability of interendothelial gap junctions
      using the scrape-loading method did not show a change in function in the septic
      group. Finally, a time-course study was designed to test for a possible
      association of enhanced Cx40 expression with endothelial dysfunction. Endothelium
      dependent relaxation was diminished in rings of aorta when harvested from septic
      rats before (6 hrs after surgery) but not at the time when enhanced Cx40
      expression occurred (12 and 24 hrs). CONCLUSION: In this experimental model,
      recovery from an early transient dysfunction of the aortic endothelium is
      associated with an enhanced expression of aortic endothelial Cx40.

PMID- 15942349
TI  - Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4
      methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model.
AB  - OBJECTIVE: Hyperthermia is a potentially fatal manifestation of severe 3,4
      methylenedioxymethamphetamine (MDMA, Ecstasy) intoxication. No proven effective
      drug treatment exists to reverse this potentially life-threatening hyperthermia,
      likely because mechanisms of peripheral thermogenesis are poorly understood.
      Using a rat model of MDMA hyperthermia, we evaluated the acute drug-induced
      changes in plasma catecholamines and used these results as a basis for the
      selection of drugs that could potentially reverse this hyperthermia. DESIGN:
      Prospective, controlled, randomized animal study. SETTING: A research institute
      laboratory. SUBJECTS: Male, adult Sprague-Dawley rats. INTERVENTIONS: Based on
      MDMA-induced changes in plasma catecholamine levels, rats were subjected to the
      nonselective (beta1 + beta2) adrenergic receptor antagonists propranolol or
      nadolol or the alpha1- + beta1,2,3-adrenergic receptor antagonist carvedilol
      before or after a thermogenic challenge of MDMA. MEASUREMENT AND MAIN RESULTS:
      Plasma catecholamines levels 30 mins after MDMA (40 mg/kg, subcutaneously) were
      determined by high-pressure liquid chromatography and electrochemical detection.
      Core temperature was measured by a rectal probe attached to a thermocouple. Four
      hours after MDMA treatment, blood was drawn and serum creatine kinase levels were
      measured as a marker of rhabdomyolysis using a Vitros analyzer. MDMA induced a 35
      fold increase in norepinephrine levels, a 20-fold increase in epinephrine, and a
      2.4-fold increase in dopamine levels. Propranolol (10 mg/kg, intraperitoneally)
      or nadolol (10 mg/kg, intraperitoneally) administered 30 mins before MDMA had no
      effect on the thermogenic response. In contrast, carvedilol (5 mg/kg,
      intraperitoneally) administered 15 mins before or after MDMA prevented this
      hyperthermic response. Moreover, when administered 1 hr after MDMA, carvedilol
      completely reversed established hyperthermia and significantly attenuated
      subsequent MDMA-induced creatine kinase release. CONCLUSION: These data show that
      alpha1 and beta3-adrenergic receptors may contribute to the mediation of MDMA
      induced hyperthermia and that drugs targeting these receptors, such as
      carvedilol, warrant further investigation as novel therapies for the treatment of
      psychostimulant-induced hyperthermia and its sequelae.

PMID- 15942350
TI  - Brief inhalation of low-dose carbon monoxide protects rodents and swine from
      postoperative ileus.
AB  - OBJECTIVE: Carbon monoxide (CO), an endogenous byproduct of heme metabolism, is
      produced at high levels in injured tissue via induction of heme-oxygenase-1
      activity, where it contributes to the modulation of proinflammatory processes.
      Alone, CO has potent anti-inflammatory effects in models of acute and chronic
      inflammation. In rodents, inhalation of low concentrations of CO (250 ppm) for 24
      hrs protects against postoperative gastrointestinal ileus. The current study
      determined whether shorter exposures and lower concentrations were equally
      protective and whether CO treatment would be effective in a large animal species
      (swine) managed under conditions approximating the clinical setting. DESIGN:
      Dosing studies were first performed in rats by exposing them to CO (30-250 ppm)
      or air by inhalation for 1 or 3 hrs before anesthesia. An effective dosing
      regimen was then selected for testing in swine. Postoperative ileus in both
      species was induced by laparotomy and mild compression (running) of the small
      intestine. MEASUREMENTS AND MAIN RESULTS: In rats, inhalation of 75 ppm CO for 3
      hrs before anesthesia and surgery ameliorated the surgically induced delay in
      gastrointestinal transit to levels achieved using 250 ppm for 24 hrs. Swine
      treated with 250 ppm CO for the same time period exhibited significantly improved
      postoperative intestinal circular muscle contractility in vitro and
      gastrointestinal transit in vivo. Carboxyhemoglobin concentrations measured after
      termination of CO exposure averaged 5.8% (baseline, 1.5%). No deleterious effects
      on heart rate, oxygen saturation, blood chemistries, and serum electrolytes were
      observed. CONCLUSIONS: These findings demonstrate that inhalation of a low
      concentration of CO before surgery attenuates postoperative ileus in rodents and,
      more importantly, in a large animal species without risk to well-being during
      surgery or perioperatively. Exposures need not be prolonged, with significant
      benefit occurring with a 3-hr pretreatment.

PMID- 15942351
TI  - "Renal dose" dopamine is associated with the risk of new-onset atrial
      fibrillation after cardiac surgery.
AB  - OBJECTIVE: "Renal dose" dopamine (rDA; 1-3 microg/kg per min) is administered to
      patients after cardiac surgery to preserve or improve renal function. Many of
      these patients develop new-onset postoperative atrial fibrillation or atrial
      flutter (pAF) that could be related to rDA administration. The objective of this
      investigation was to determine whether there was an association between rDA and
      new-onset pAF in patients undergoing coronary artery bypass grafting with
      cardiopulmonary bypass (CABG). SETTING: Research hospital. SUBJECTS: The study
      population consisted of 1,731 patients undergoing CABG. INTERVENTIONS: CABG with
      and without rDA. DESIGN: After approval by the institutional review board, a
      retrospective study using the Cardiothoracic Anesthesia Patient Registry was
      undertaken to determine the association between rDA and pAF in patients
      undergoing CABG. Patients with a documented history of atrial fibrillation, those
      who required inotrope use during or after surgery, and those having valve surgery
      were excluded. MEASUREMENTS AND MAIN RESULTS: One-thousand seven-hundred thirty
      one patients undergoing CABG during the period of January 1, 2000, through June
      30, 2002, were the study population; of these, 15.0% (260/1,731) developed pAF.
      The incidence of pAF was 23.3 % (41/176) among patients who received rDA and
      14.1% (219/1,555) among those who did not receive rDA. In the multivariable
      logistic regression model, patient age, gender, chronic obstructive pulmonary
      disease or asthma, and rDA were associated with pAF (p < .01). Receipt of rDA
      increased the odds of developing pAF by 74%, independent of the effect of other
      variables. CONCLUSIONS: Renal-dose dopamine is associated with a 1.74 odds ratio
      of pAF developing after CABG.

PMID- 15942352
TI  - Pulmonary oxidant stress in murine sepsis is due to inflammatory cell nitric
      oxide.
AB  - OBJECTIVE: Pulmonary oxidant stress is an important pathophysiologic feature of
      acute lung injury. It is unclear whether nitric oxide contributes to this oxidant
      stress. Thus, we examined the role of inducible nitric oxide synthase (iNOS) in
      pulmonary oxidant stress in murine sepsis and the differential contribution of
      different cellular sources of iNOS. DESIGN: Randomized, controlled animal study.
      SETTING: Research laboratory of an academic institution. SUBJECTS: Male iNOS+/+,
      iNOS-/- C57Bl/6 mice, and bone-marrow transplanted iNOS chimeric mice: +to- (wild
      type iNOS+/+ donor bone-marrow transplanted into iNOS-/- recipient mice) and the
      reciprocal -to+ chimeras. INTERVENTIONS: Animals were randomized to sepsis (n =
      264), induced by cecal ligation and perforation, vs. naive groups (n = 138).
      MEASUREMENTS AND MAIN RESULTS: In septic iNOS-/- vs. wild-type iNOS+/+ mice,
      sepsis-induced pulmonary oxidant stress (33 +/- 11 [mean +/- sem] vs. 365 +/- 48
      pg 8-isoprostane/mg protein, p < .01) and nitrosative stress (0.0 +/- 0.0 vs. 0.9
      +/- 0.4 micromol 3-nitrotyrosine/mmol para-tyrosine, p < .05) were abolished,
      despite similar septic increases in pulmonary myeloperoxidase activity in both
      (86 +/- 20 vs. 83 +/- 12 mU/mg protein, p = .78). In +to- iNOS chimeric mice
      (iNOS localized only to donor bone-marrow-derived inflammatory cells), cecal
      ligation and perforation resulted in significant pulmonary oxidant stress (368 +/
      81 pg 8-isoprostane/mg protein) and nitrosative stress (0.6 +/- 0.2 micromol 3
      nitrotyrosine/mmol para-tyrosine), similar in degree to septic wild-type mice. In
      contrast, pulmonary oxidant and nitrosative stresses were absent in septic -to+
      iNOS chimeras (iNOS localized only to recipient parenchymal cells), similar to
      iNOS-/- mice. CONCLUSIONS: In murine sepsis-induced acute lung injury, pulmonary
      oxidant stress is completely iNOS dependent and is associated with tyrosine
      nitration. Moreover, pulmonary oxidant stress and nitrosative stress were
      uniquely dependent on the presence of iNOS in inflammatory cells (e.g.,
      macrophages and neutrophils), with no apparent contribution of iNOS in pulmonary
      parenchymal cells. iNOS inhibition targeted specifically to inflammatory cells
      may be an effective therapeutic approach in sepsis and acute lung injury.

PMID- 15942353
TI  - Effects of hypothermia for a short period on histologic outcome and extracellular
      glutamate concentration during and after cardiac arrest in rats.
AB  - OBJECTIVE: To evaluate the therapeutic effects of hypothermia for a short period
      (20 mins, 31 degrees C) using a cardiac arrest model (5 mins) in rats. DESIGN:
      Prospective animal study. SETTING: Experimental laboratory in a university
      hospital. SUBJECTS: Male Wistar rats (n = 42). INTERVENTION: Direct current (DC)
      potential and extracellular glutamate concentrations (microdialysis) were
      monitored in the hippocampal region. Histologic observation was performed 7 days
      later. MEASUREMENTS AND MAIN RESULTS: No animal died or showed severe
      complications as a result of hypothermia for a short period. In nontreated
      animals (group F), extracellular glutamate concentration simultaneously increased
      with the onset of membrane depolarization and continued to increase during the
      reperfusion period (maximum, 212% +/- 40% of the pre-ischemia level) until the
      onset of DC recovery. In animals in which hypothermia was initiated before the
      onset of ischemia (group A), extracellular glutamate concentration did not
      increase during the ischemia period. When hypothermia was initiated at the onset
      of resuscitation (group B), the glutamate concentration immediately decreased. In
      animals in which hypothermia was initiated at 4.9 +/- 1.3 mins (immediately after
      DC recovery, group C), 10 mins (group D), and 20 mins (group E) after the onset
      of resuscitation, changes in extracellular glutamate concentration were the same
      as those in nontreated animals. The percentage of injured neurons was
      significantly attenuated (compared with group F, 82% +/- 10%) when hypothermia
      was initiated before DC recovery (group A, 5% +/- 3%; group B, 29% +/- 22%) or
      immediately after DC recovery (group C, 58% +/- 18%, 9.9 +/- 1.3 mins after the
      onset of ischemia). CONCLUSIONS: Hypothermia for a short period decreased
      glutamate concentration when it was initiated before DC recovery and attenuated
      neuronal damage when it was initiated before or immediately after DC recovery.
      The therapeutic time window for hypothermia for a short period is about 10 mins
      after the onset of ischemia.

PMID- 15942354
TI  - Extracorporeal venovenous cooling for induction of mild hypothermia in human
      sized swine.
AB  - OBJECTIVE: Several cooling methods have been investigated for inducing mild
      hypothermia (33-36 degrees C) after cardiac arrest, brain trauma, or stroke. To
      achieve its best effect, therapeutic hypothermia has to be applied very early
      after the ischemic insult; otherwise, the beneficial effect would be diminished
      or even abrogated. The aim of this study was to investigate the effectiveness and
      safety of extracorporeal venovenous cooling as compared with endovascular
      cooling. DESIGN: Swine were cooled in a randomized crossover design from 38
      degrees C to 33 degrees C brain temperature, either with extracorporeal
      venovenous cooling or with endovascular cooling. SETTING: Laboratory
      investigation. SUBJECTS: Six swine of human size (85 to 101 kg). INTERVENTIONS:
      Swine were randomly cooled with the first device, and after achieving the target
      brain temperature, re-warmed via the same technique and with heating lamps to
      baseline temperature. Then the other catheter was inserted and cooling was
      performed with the second device. MEASUREMENTS: Brain, pulmonary artery and
      tympanic temperature, blood pressure, and heart rate were recorded continuously.
      Laboratory samples, including free hemoglobin, were taken at predefined
      temperature points during cooling. Comparisons between and within (baseline vs.
      33 degrees C) the treatment groups were performed with the paired Student's t
      test. MAIN RESULTS: The time needed to reduce brain temperature from 38.0 degrees
      C to 33.0 degrees C was 41 +/- 17 mins with venovenous cooling and 126 +/- 37
      mins with endovascular cooling (p = .001). Heart rate and mean arterial pressure
      decreased moderately during cooling and were significantly lower at 33 degrees C
      than at baseline in both groups, without differences between groups. None of the
      swine developed significant hemolysis, arrhythmias, or bleeding. CONCLUSIONS:
      Extracorporeal venovenous cooling was an effective and safe method to rapidly
      induce therapeutic mild hypothermia in human-sized swine. It seems to be
      promising for further application and investigation in patients.

PMID- 15942355
TI  - Pulmonary contusion causes impairment of macrophage and lymphocyte immune
      functions and increases mortality associated with a subsequent septic challenge.
AB  - OBJECTIVE AND DESIGN: Pulmonary contusion is frequently followed by acute
      respiratory distress syndrome, pneumonia, and sepsis. However, immunologic
      alterations of circulating and resident immune cell populations contributing to
      the posttraumatic immunosuppression are poorly understood. We therefore
      characterized the influence of pulmonary contusion on peripheral blood
      mononuclear cells, peritoneal macrophages, splenocytes, and splenic macrophages.
      To address the significance of the immunosuppression associated with lung
      contusion, we investigated how the consecutive addition of moderate or severe
      sepsis affected survival after blunt chest trauma. SUBJECTS: Male C3H/HeN mice (n
      = 10 per group) were anesthetized and subjected to chest trauma or sham
      procedure. MEASUREMENTS: The cytokine release of cultured peripheral blood
      mononuclear cells, peritoneal macrophages, splenocytes, and splenic macrophages
      and plasma levels of tumor necrosis factor-alpha and interleukin-6 from those
      animals were quantified. Sepsis was induced via cecal ligation and puncture 24
      hrs after lung contusion. MAIN RESULTS: Two hours after blunt chest trauma,
      plasma tumor necrosis factor-alpha and interleukin-6 were markedly increased, as
      was peripheral blood mononuclear cell cytokine production, lung myeloperoxidase
      activity, and lung chemokine concentrations. At 24 hrs and, in part, already at 2
      hrs, cytokine release from peritoneal macrophages, splenic macrophages, and
      splenocytes was significantly suppressed. Furthermore, pulmonary contusion when
      followed by moderate sepsis significantly diminished survival rate when compared
      with chest trauma or moderate sepsis alone. CONCLUSIONS: These results indicate
      that pulmonary contusion causes severe immunodysfunction of splenocytes,
      macrophages, and monocytes in different local compartments and systemically.
      Moreover, this immunosuppression is associated with an increased susceptibility
      to infectious complications, which results in a decreased survival rate if blunt
      chest trauma is followed by a septic insult.

PMID- 15942356
TI  - Regulation of peritoneal and systemic neutrophil-derived tumor necrosis factor
      alpha release in patients with severe peritonitis: role of tumor necrosis factor
      alpha converting enzyme cleavage.
AB  - OBJECTIVE: Polymorphonuclear neutrophil (PMN) influx and peritoneal tumor
      necrosis factor (TNF)-alpha production are key host defense mechanisms during
      peritonitis. The aim of this study was to explore the potential interactions
      between TNF-alpha production and TNF-alpha converting enzyme (TACE) expression by
      PMN in the blood and peritoneum of patients with severe peritonitis. DESIGN: A
      prospective study. SETTING: A surgical adult intensive care unit in a university
      hospital. PATIENTS: A total of 29 consecutive immunocompetent patients with
      severe sepsis within 48 hrs of onset were enrolled and underwent laparotomy for a
      diffuse secondary peritonitis. Thirteen volunteers served as controls.
      MEASUREMENTS: Blood and peritoneal fluid recovered during laparotomy were
      analyzed and compared for 1) soluble TNF-alpha, soluble L-selectin, and type I
      and II TNF-alpha receptor levels; 2) PMN membrane TNF-alpha, membrane L-selectin,
      and TACE expression (flow cytometry); and 3) TNF-alpha production by cultured
      PMN. Correlations between these forms of PMN-derived TNF-alpha and the severity
      of the peritonitis and patient's outcome were investigated. MAIN RESULTS:
      Elevated soluble TNF-alpha levels in both plasma and peritoneal fluid from the
      patients were found, together with decreased expression of membrane TNF-alpha and
      TACE up-regulation at the PMN surface. Soluble L-selectin and type I and II TNF
      receptors were highly released, suggesting also the role of TACE. In contrast,
      the capacity of both blood and peritoneal PMN to synthesize TNF-alpha in vitro,
      in optimal conditions of stimulation (lipopolysaccharide + interferon-gamma), was
      impaired as compared with controls' blood PMN. Regulation of PMN-derived TNF
      alpha was similar in the two compartments, but responses were more pronounced in
      the peritoneum. TACE up-regulation at the surface of blood-derived PMN correlated
      with the Sequential Organ Failure Assessment score and vital outcome. CONCLUSION:
      These human data demonstrate that mTACE is up-regulated at the PMN surface during
      severe peritonitis. This finding could be related to a paracrine regulatory loop
      involving some TACE substrates such as TNF-alpha, L-selectin, and TNF receptors.

PMID- 15942357
TI  - Low molecular weight heparin attenuates multiple organ failure in a murine model
      of disseminated intravascular coagulation.
AB  - OBJECTIVE: Bacterial sepsis causes widespread vascular inflammation that
      frequently leads to disseminated intravascular coagulation (DIC). Although
      intravascular coagulation contributes to organ failure, it is often debated
      whether anticoagulant therapy produces any beneficial effects in patients with
      DIC. The aim of this study was to document potential beneficial effects of low
      molecular weight heparin (LMWH) in a lipopolysaccharide-induced DIC model.
      DESIGN: Controlled animal experiment combined with an in vitro laboratory study.
      SETTING: Academic research laboratory. SUBJECTS: C57BL/6 mice subjected to two
      injections of Serratia Marcescens lipopolysaccharide (LPS) resulting in the
      generalized Shwartzman's reaction as a model for DIC. INTERVENTIONS: LMWH (5 IU
      of anti-Xa activity) or saline was administered before both LPS injections and 10
      hrs after the first exposure to LPS. To test the effect of LMWH on LPS-driven
      monocyte inflammatory responses, a human monocyte-human umbilical vein
      endothelial cell co-culture was used to determine E-selectin expression as a
      marker of monocyte adherence. MEASUREMENTS AND MAIN RESULTS: In our murine DIC
      model, LMWH had no effect on markers of inflammation. In addition, no effect of
      LMWH was detected on monocyte adherence in the human monocyte-human umbilical
      vein endothelial cell co-culture. Organ damage, contrarily, was significantly
      reduced as determined by hepatic necrosis (p < .05), lung epithelial protein
      leakage (p < .05), and creatinine release from kidneys into plasma (p < .01).
      LMWH protection from organ failure resulted in an increase in survival (p = .06)
      in this model for DIC. CONCLUSIONS: These results demonstrate the significance of
      blood coagulation in the progression of DIC and hint at a beneficial role for
      LMWH anticoagulation in the management of DIC.

PMID- 15942358
TI  - Short-term outcomes in older intensive care unit patients with dementia.
AB  - OBJECTIVE: To determine the impact of dementia on the outcomes of intensive care
      unit (ICU) care and use of ICU interventions among older patients. DESIGN:
      Prospective observational cohort study. SETTING: Urban university teaching
      hospital. PATIENTS: Patients were 395 patients age >/=65 consecutively admitted
      to a medical ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Dementia
      was determined by a previously validated proxy measure, the Modified Blessed
      Dementia Rating Scale. We chose cut points to focus on patients with moderate
      severe dementia at baseline. Our primary outcomes included length of mechanical
      ventilation and ICU and hospital length of stay. Secondary outcomes included ICU
      readmission, changes in code status, discharge location, mortality, and use of
      ICU interventions. Medical record abstraction was performed to determine the
      rates of ICU outcomes, use of ICU interventions, and potential confounders. Our
      study documented a prevalence of moderate-severe dementia of 17% in patients age
      >/=65 admitted to the ICU. Patients with dementia were significantly older (80
      vs. 76), more likely to be female (65% vs. 52%), and more likely to be admitted
      from a nursing home (46% vs. 11%). Patients with dementia had significantly
      higher Acute Physiology and Chronic Health Evaluation II scores on admission to
      the ICU (25 vs. 23). Patients with dementia were more likely to have their code
      status changed to less aggressive in the ICU (24% vs. 14%). There was no
      significant difference in readmission to the ICU, discharge location, ICU or
      hospital mortality rate, or use of ICU interventions between patients with and
      without dementia. CONCLUSIONS: Our study documents no difference in outcomes from
      ICU care in older patients with and without dementia. There was no increased
      short-term mortality rate in older patients with dementia compared with those
      without dementia after admission to the ICU. Presumptions that outcomes from
      critical care are less favorable in patients with dementia should not drive
      treatment decisions in the ICU.

PMID- 15942359
TI  - Resuscitation from experimental heatstroke by transplantation of human umbilical
      cord blood cells.
AB  - OBJECTIVE: Human umbilical cord blood cells (HUCBCs) are effective in the
      treatment of conventional stroke in experimental models. In the study described
      herein, we administered HUCBCs into the femoral vein or directly into the
      cerebral ventricular system and assessed their effects on circulatory shock,
      cerebral ischemia, and damage during heatstroke. DESIGN: Controlled, prospective
      study. SETTING: Hospital medical research laboratory. SUBJECTS: Sprague-Dawley
      rats (287 +/- 16 g body weight, males). INTERVENTIONS: Anesthetized rats,
      immediately after the onset of heatstroke, were divided into four major groups
      and given the following: a) normal saline or AIM-V medium intravenously (0.3 mL)
      or intracerebroventricularly (10 microL); b) peripheral blood mononuclear cells
      (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V
      medium, intracerebroventricularly); or c) HUCBCs (5 x 10 in 0.3 mL AIM-V medium,
      intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly).
      Another group of rats, under urethane anesthesia, were exposed to room
      temperature (26 degrees C) and used as normothermic controls. Urethane
      anesthetized animals were exposed to an ambient temperature of 43 degrees C to
      induce heatstroke. Their physiologic and biochemical parameters were continuously
      monitored. MEASUREMENTS AND MAIN RESULTS: When the vehicle-treated rats underwent
      heat exposure, their survival time values were found to be 21-23 mins.
      Resuscitation with intravenous or intracerebroventricular doses of HUCBCs, but
      not peripheral blood mononuclear cells, immediately at the onset of heatstroke
      significantly improved survival during heatstroke (61-148 mins). As compared with
      values for normothermic controls, the vehicle-treated heatstroke rats had lower
      mean arterial pressure, cerebral blood flow, and brain PO2 values but higher
      intracranial pressure and cerebral ischemia values and more injury markers. The
      circulatory shock, intracranial hypertension, cerebral hypoperfusion and hypoxia,
      increment of cerebral ischemia, and damage markers during heatstroke were all
      significantly attenuated by intravenous or intracerebroventricular delivery of
      HUCBCs but not peripheral blood mononuclear cells. CONCLUSIONS: We successfully
      demonstrate that HUCBC therapy may resuscitate heatstroke victims by reducing
      circulatory shock and cerebral ischemic injury; central delivery of HUCBCs seems
      superior to systemic delivery of HUCBCs in resuscitating patients with
      heatstroke.

PMID- 15942361
TI  - Primer on medical management of severe brain injury.
AB  - OBJECTIVE: To review the current understanding of the medical management of
      severe brain injury. DATA SOURCE: The MEDLINE database, bibliographies of
      selected articles, and current English-language texts on the subject. STUDY
      SELECTION: Studies related to management of intracranial hypertension, traumatic
      brain injury, and brain edema. DATA EXTRACTION: All studies relevant to the
      subject under consideration were considered, with a focus on clinical studies in
      adults. DATA SYNTHESIS: Basic rules of resuscitation must apply, including
      adequate ventilation, appropriate fluid administration, and cardiovascular
      support. The control of intracranial pressure can be considered in three steps.
      The first step should be initial slight hyperventilation with a target PaCO2 of
      35 mm Hg and cerebrospinal fluid drainage for intracranial pressure of >15-20 mm
      Hg. The second step should be mannitol or hypertonic saline and hyperventilation
      to target PaCO2 of 28-35 mm Hg. The third step should be barbiturate coma or
      decompressive craniectomy. Additional management issues, including seizure
      prophylaxis, sedation, nutritional support, use of hypothermia, and
      corticosteroids, are also discussed. CONCLUSIONS: Brain injury is frequently
      associated with the development of brain edema and the development of
      intracranial hypertension. However, with a coordinated, stepwise, and aggressive
      approach to management, focusing on control of intracranial pressure without
      adversely affecting cerebral perfusion pressure, outcomes can be good.

PMID- 15942360
TI  - Topical inhibition of nuclear factor-kappaB enhances reduction in lung edema by
      surfactant in a piglet model of airway lavage.
AB  - OBJECTIVE: Acute respiratory distress syndrome is occasionally seen in newborn
      infants due to a severe inflammatory process in the lungs that affects capillary
      alveolar permeability, epithelial integrity, and type I and II pneumocyte
      function. The aim of this study was to investigate the effect of a topically
      applied nuclear factor-kappaB inhibitor (IkappaB kinase-NF-kappaB essential
      modulator binding domain [IKK-NBD] peptide) on gas exchange, lung function, lung
      fluids, and inflammation in a piglet model of repeated airway lavage that is
      characterized by surfactant deficiency, lung edema, and an inflammatory response.
      DESIGN: Prospective, randomized, controlled animal study. SETTING: Research
      laboratory of a university children's hospital. SUBJECTS: A total of 24
      anesthetized, mechanically ventilated newborn piglets. INTERVENTIONS: Repeated
      airway lavage was carried out until both the Pao2 decreased to approximately 40
      mm Hg, while ventilating the piglets with an Fio2 of 0.6, and a peak inspiratory
      pressure of >/=18 cm H2O was needed to maintain tidal volume at 6 mL/kg. One
      group of piglets served as a control (n = 8), a second group (S, n = 8) received
      a porcine surfactant preparation (Curosurf), and a third group received IKK-NBD
      peptide admixed to surfactant (S+IN, n = 8). MEASUREMENTS AND MAIN RESULTS: After
      6 hrs of mechanical ventilation after intervention, S+IN group piglets showed
      decreased extravascular lung water (S+IN vs. S, 20 +/- 3 vs. 28 +/- 10 mL/kg; p <
      .05) and a lesser protein content in the epithelial lining fluid (S+IN vs. S, 38
      +/- 5 vs. 50 +/- 5 mg/L; p < .05). Functional residual capacity (S+IN vs. S, 16.7
      +/- 6.3 vs. 12.2 +/- 4.3 mL/kg; p < .05), alveolar volume (S+IN vs. S, 5.4 +/-
      1.8 vs. 4.6 +/- 1.5 mL/kg; p < .05), and lung mechanics were improved.
      Bronchoalveolar lavage showed a lesser percentage of polymorphonuclear leukocytes
      (S+IN vs. S, 70% +/- 6% vs. 82% +/- 3%; p < .01) and a reduction in the chemokine
      leukotriene B4 (S+IN vs. S, 2.0 +/- 0.6 vs. 3.5 +/- 1.4 pg/mL; p < .01).
      CONCLUSIONS: A topically applied nuclear factor-kappaB inhibitor improves lung
      edema and lung volumes and reduces inflammation in this newborn piglet model of
      airway lavage.

PMID- 15942362
TI  - Regional analgesia in the critically ill.
AB  - OBJECTIVE: The objective of this review is to analyze and describe the use of
      regional analgesia in the critically ill. DATA SOURCE: A Medline search from 1966
      to 2004 using the search terms critically ill, nerve blocks, regional analgesia,
      and regional anesthesia, as well as a search in the Cochrane library, was
      performed, and standard international textbooks related to critical care and
      regional anesthesia were searched for practice recommendations. STUDY SELECTION:
      Studies, case reports, and review articles relevant to the topic were included.
      DATA EXTRACTION AND SYNTHESIS: Data were extracted and analyzed in a descriptive
      fashion. CONCLUSION: Regional analgesia using single-injection regional blocks
      and continuous neuraxial and peripheral catheters can play a valuable role in a
      multimodal approach to pain management in the critically ill patient to achieve
      optimum patient comfort and to reduce physiologic and psychological stress. By
      avoiding high systemic doses of opioids, several complications like withdrawal
      syndrome, delirium, mental status changes, and gastrointestinal dysfunction can
      be reduced or minimized. Because of limited patient cooperation during placement
      and monitoring of continuous regional analgesia, indications for their use must
      be carefully chosen based on anatomy, clinical features of pain, coagulation
      status, and logistic circumstances. High-quality nursing care and well-trained
      physicians are essential prerequisites to use these techniques safely in the
      critical care environment.

PMID- 15942363
TI  - Mechanical ventilation and acute renal failure.
AB  - OBJECTIVE: To review the current literature on possible mechanisms by which
      mechanical ventilation may initiate or aggravate acute renal failure. DATA
      SOURCE: A Medline database and references from identified articles were used to
      perform a literature search relating to mechanical ventilation and acute renal
      failure. DATA SYNTHESIS: Acute renal failure may be initiated or aggravated by
      mechanical ventilation through three different mechanisms. First, strategies such
      as permissive hypercapnia or permissive hypoxemia may compromise renal blood
      flow. Second, through effects on cardiac output, mechanical ventilation affects
      systemic and renal hemodynamics. Third, mechanical ventilation may cause
      biotrauma-a pulmonary inflammatory reaction that may generate systemic release of
      inflammatory mediators. The harmful effects of mechanical ventilation may become
      more significant when a comorbidity is present. In these situations, it is more
      difficult to maintain normal gas exchange, and moderate arterial hypoxemia and
      hypercapnia are often accepted. Renal blood flow is compromised due to a
      decreased cardiac output as a consequence of high intrathoracic pressures.
      Furthermore, the effects of biotrauma are not limited to the lungs but may lead
      to a systemic inflammatory reaction. CONCLUSIONS: The development of acute renal
      failure during mechanical ventilation likely represents a multifactorial process
      that may become more important in the presence of comorbidities. Development of
      optimal interventional strategies requires an understanding of physiologic
      principles and greater insight into the precise molecular and cellular mechanisms
      that may also play a role.

PMID- 15942364
TI  - Plasma platelet-activating factor acetylhydrolase activity in critically ill
      patients.
AB  - OBJECTIVE: Platelet-activating factor (PAF) is a potent proinflammatory mediator
      in systemic inflammation and sepsis and is inactivated by the enzyme PAF
      acetylhydrolase (PAF-AH). Recently, a large phase III clinical trial using
      recombinant PAF-AH to treat patients with severe sepsis was performed but failed
      to reduce 28-day mortality rate. To get more information on the activity of PAF
      AH in sepsis, we repeatedly measured its activity in plasma in critically ill
      patients compared with healthy controls. DESIGN: Retrospective cohort study.
      SETTING: Intensive care unit. PATIENTS: Two hundred thirty-one patients who were
      admitted to an operative intensive care unit within 1 yr were enrolled and
      evaluated daily for American College of Chest Physicians/Society of Critical Care
      Medicine criteria. PAF-AH activity was measured as the release of [H]-acetate
      from [H]-acetyl-PAF. INTERVENTIONS: Analysis of plasma samples. MEASUREMENTS AND
      MAIN RESULTS: At the day of admission, PAF-AH activity of patients was below
      controls but markedly increased over time. Higher activities were seen in
      patients with severe sepsis or septic shock compared with those without organ
      failure. With respect to the clinical outcome, lower values were found in
      nonsurvivors only as long as they had not developed organ failure. In severe
      sepsis/septic shock, values of nonsurvivors exceeded those of survivors. PAF-AH
      activity was positively correlated with plasma levels of inflammatory mediators
      such as neopterine and tumor necrosis factor-alpha but not with acute phase
      reactants such as C-reactive protein, interleukin-6, or PCT. In addition,
      parenteral nutrition with lipid emulsions was seemingly associated with low PAF
      AH activity compared with enteral nutrition. CONCLUSION: The data indicate
      severity- and time-dependent changes in PAF-AH activity and may help to explain
      the failure of recombinant PAF-AH treatment strategies that were not based on
      activity measurements.

PMID- 15942365
TI  - Blood transfusion and the development of acute respiratory distress syndrome:
      more evidence that blood transfusion in the intensive care unit may not be
      benign.

PMID- 15942366
TI  - Einstein, quantum mechanics, and delirium.

PMID- 15942367
TI  - Glutamine and heat shock proteins: one more approach to lung injury.

PMID- 15942368
TI  - Fast hug, Cartesians, and the World Series.

PMID- 15942369
TI  - Real-time ultrasonography--should this be available to every critical care
      physician?

PMID- 15942370
TI  - Jumpers, fallers, and stumblers: children should not drop and elders should not
      trip.

PMID- 15942371
TI  - Water, water, everywhere...but how do we measure it?

PMID- 15942372
TI  - Slow response times: is it the pneumonia or the physician?

PMID- 15942373
TI  - Lower cortisol concentrations in patients with liver disease: more adrenal
      failure or more confusion?

PMID- 15942374
TI  - Delirium: out of one, many...

PMID- 15942375
TI  - The importance of understanding the costs of critical care and mechanical
      ventilation.

PMID- 15942376
TI  - Limitation and withdrawal practice patterns in India.

PMID- 15942377
TI  - Catheter-related infection can be prevented...if we take the arterial line
      seriously too!

PMID- 15942378
TI  - Determination of troponin in the intensive care unit patient: please avoid
      "troponinitis"!

PMID- 15942379
TI  - Peptidoglycan: just another marker of postoperative infections or a mediator of
      disease?

PMID- 15942380
TI  - Sepsis and vascular dysfunction: connections with endothelial connexin 40.

PMID- 15942381
TI  - Toward directed therapy for amphetamine-mediated hyperthermia: is carvedilol
      worth raving about?

PMID- 15942382
TI  - Carbon monoxide and ileus: inhaled gas to prevent retained gas?

PMID- 15942383
TI  - Renal-dose dopamine: another nail in the coffin.

PMID- 15942384
TI  - The answer is always NO.

PMID- 15942385
TI  - Early induction of hypothermia: will sooner be better?

PMID- 15942386
TI  - In search of the silver bullet: fast and safe cooling for brain injury?

PMID- 15942387
TI  - Immunosuppression after trauma.

PMID- 15942388
TI  - Caught in the act: observation of polymorphonuclear neutrophils for the
      regulation of tumor necrosis factor-alpha release by tumor necrosis factor-alpha
      converting enzyme in patients with secondary peritonitis.

PMID- 15942389
TI  - Heparins in sepsis-induced disseminated intravascular coagulation: low weight
      high impact?

PMID- 15942390
TI  - Dementia: a justification for limiting intensive care?

PMID- 15942391
TI  - Should we add stem cells to the code cart in resuscitation of heatstroke?

PMID- 15942392
TI  - Lung injury and renal failure: from protective ventilation to renal protection.

PMID- 15942393
TI  - Plasma platelet-activating factor acetylhydrolase is a dynamic variable in
      critical illness: In the end, is change good for you?

PMID- 15942395
TI  - Critical illness brain syndrome (CIBS): an underestimated entity?

PMID- 15942397
TI  - Why not implement the fundamental critical care support (FCCS) course?

PMID- 15942399
TI  - Increased awareness.

PMID- 15942401
TI  - Forums for expressing concerns.

PMID- 15942402
TI  - The right circumscript populations.

PMID- 15942403
TI  - Monitoring intra-cuff pressure in subglottic aspiration.

PMID- 15942407
TI  - The prothrombin time point of the disseminated intravascular coagulation score.

PMID- 15942408
TI  - The definitive position on early nutritional support is yet to be established.

PMID- 15942409
TI  - Tidal volumes and the acute respiratory distress syndrome.

PMID- 15942411
TI  - Adrenergic mechanisms and blood-brain barrier permeability.

PMID- 15942414
TI  - Quality of life evaluation in cardiovascular disease: a role for the European
      Society of Cardiology?

PMID- 15942415
TI  - Relaxation therapy for rehabilitation and prevention in ischaemic heart disease:
      a systematic review and meta-analysis.
AB  - AIMS: To establish the effects of relaxation therapy on the recovery from a
      cardiac ischaemic event and secondary prevention. METHODS AND RESULTS: A search
      was conducted for controlled trials in which patients with myocardial ischaemia
      were taught relaxation therapy, and outcomes were measured with respect to
      physiological, psychological, cardiac effects, return to work and cardiac events.
      A total of 27 studies were located. Six studies used abbreviated relaxation
      therapy (3 h or less of instruction), 13 studies used full relaxation therapy (9
      h of supervised instruction and discussion), and in eight studies full relaxation
      therapy was expanded with cognitive therapy (11 h on average). Physiological
      outcomes: reduction in resting heart rate, increased heart rate variability,
      improved exercise tolerance and increased high-density lipoprotein cholesterol
      were found. No effect was found on blood pressure or cholesterol. Psychological
      outcome: state anxiety was reduced, trait anxiety was not, depression was
      reduced. Cardiac effects: the frequency of occurrence of angina pectoris was
      reduced, the occurrence of arrhythmia and exercise induced ischaemia were
      reduced. Return to work was improved. Cardiac events occurred less frequently, as
      well as cardiac deaths. With the exception of resting heart rate, the effects
      were small, absent or not measured in studies in which abbreviated relaxation
      therapy was given. No difference was found between the effects of full or
      expanded relaxation therapy. CONCLUSION: Intensive supervised relaxation practice
      enhances recovery from an ischaemic cardiac event and contributes to secondary
      prevention. It is an important ingredient of cardiac rehabilitation, in addition
      to exercise and psycho-education.

PMID- 15942416
TI  - Prevalence and predictors of smoking in Pakistan: results of the National Health
      Survey of Pakistan.
AB  - OBJECTIVE: We analysed data collected during a nationwide cross-sectional
      household survey to estimate the prevalence of and identify factors associated
      with smoking in Pakistan. DESIGN: Population-based, cross-sectional survey
      [National Health Survey of Pakistan (NHSP) 1990-1994]. METHODS: A population
      based survey was carried out in Pakistan during 1990-1994. A nationally
      representative sample of 18,135 individuals aged 6 months and older was surveyed.
      We restricted this analysis to individuals aged 15 years or older (n=9442). The
      main outcome measure was self-reported smoking. Smokers were defined as
      individuals who reported current smoking and having smoked at least 100
      cigarettes or 'beddies' during their lifetime. RESULTS: Overall prevalence of
      smoking was 15.2% [95% confidence interval (CI), 14.5-15.9%]. It was 28.6% (27.3
      29.9%) among men and 3.4% (2.9-3.9%) among women. The highest prevalence was
      reported in men aged 40-49 years (40.9%). The independent predictors of smoking
      identified in the multivariate logistic regression analysis included age, male
      gender, ethnicity and illiteracy. CONCLUSIONS: One out of every two to three
      middle-aged men in Pakistan smoke cigarettes. Our findings suggest that
      ethnically sensitive smoking control programmes that include measures for
      improving literacy rates are needed in Pakistan.

PMID- 15942417
TI  - Trends in coronary heart disease in France during the second half of the 1990s.
AB  - BACKGROUND: Data on the recent evolution in coronary heart disease (CHD)
      mortality and incidence rates are lacking in France. This paper aims to
      investigate whether the declining trends observed from 1985-1993 still persist in
      the second half of the 1990s. METHODS: Population registers of acute CHD have
      been implemented in three specific geographical areas, first as part of the
      MONICA Project (1985-1993) and, since 1997, according to a simplified
      registration procedure. Weighted Poisson regressions have been used to
      investigate time trends in CHD events in men and women aged 35-64 after
      correction for registration differences. RESULTS: Data obtained from 1997-2000
      showed that the north-to-south gradient of decreasing frequency of CHD events in
      France was still present. Besides, they revealed no specific trend in CHD
      morbidity by centre and gender, except in Lille (in the north of France) where
      events tended to increase in women. Coronary heart disease mortality rates in
      recent years were decreasing in men, particularly in the north and east of
      France, but were stable in women with, even, a rising tendency in the north.
      CONCLUSION: The decreasing trend in CHD events in France observed from the mid
      1980s to the early 1990s seemed to markedly slow down in the second half of the
      1990s.

PMID- 15942418
TI  - C-reactive protein and cardiorespiratory fitness in young adults.
AB  - BACKGROUND: Fitness and obesity are both independently associated with
      cardiovascular events and mortality. C-reactive protein (CRP), a predictor of
      cardiovascular events is associated with obesity; but its association with
      cardiorespiratory fitness in early adulthood is uncertain. The aim of this study
      was to examine the relationship between cardiorespiratory fitness and CRP,
      controlling for obesity in an unselected cohort of young adults. DESIGN: A cross
      sectional study in a representative birth cohort. METHODS: We measured CRP
      levels, cardiorespiratory fitness, anthropometric variables, blood pressure and
      smoking in 26-year-old men (n=400) and women (n=315). Log CRP levels were
      compared across cardiorespiratory fitness with adjustment for body mass index
      (BMI), sex, blood pressure, smoking and combined oral contraceptive use. RESULTS:
      Geometric mean CRP levels were higher in women (3.23 mg/l, 95% CI 2.85-3.64)
      compared with men (1.70 mg/l, 1.52-1.89). Regression analysis adjusting for sex
      and weight showed an inverse association between fitness and CRP (beta=-0.16,
      P<0.001). This association held after statistical controls were added for BMI,
      systolic blood pressure and smoking and combined oral contraceptive use (P< or
      =0.01). CONCLUSIONS: Cardiorespiratory fitness levels are inversely associated
      with CRP levels in young adults independent of obesity, blood pressure, smoking
      and combined oral contraceptive use in women. Physical fitness may decrease the
      risk of cardiovascular events by reducing inflammation.

PMID- 15942419
TI  - Heart rate variability is associated with haptoglobin phenotype in patients with
      coronary artery disease.
AB  - BACKGROUND: Three haptoglobin phenotypes exist called Hp 1-1, Hp 2-2, and Hp 2-1.
      Patients carrying the haptoglobin 1 allele seem to be partly protected against
      coronary artery disease. An attenuated heart rate variability is associated with
      a poor outcome in patients with coronary artery disease. Therefore, we
      hypothesized that the presence of the haptoglobin 1 allele would be associated
      with a favourable heart rate variability. DESIGN: A cross-sectional study.
      METHODS: We included 255 patients who were referred for elective coronary
      angiography as a result of suspected coronary artery disease, and all underwent
      24-h electrocardiogram recordings to assess heart rate variability in the time
      domain. The haptoglobin phenotype was also determined in each patient. RESULTS:
      There were 159 patients in the Hp 1-1 and Hp 2-1 groups and 98 patients in the Hp
      2-2 group. The two groups were comparable with respect to clinical parameters.
      However, the Hp 2-2 group had significantly lower 24-h heart rate variability
      values compared with the other group (RR 882 versus 921 ms, P=0.02; RMSSD 26
      versus 30 ms, P<0.01; pNN50 6 versus 9%, P=0.01). Furthermore, Hp 2-2 was
      independently and negatively associated with heart rate variability (P=0.02).
      CONCLUSION: Hp 2-2 was associated with an attenuated heart rate variability in
      patients with coronary artery disease that may help to explain other results
      reporting a poor prognosis in Hp 2-2 patients.

PMID- 15942420
TI  - Comparison of low-frequency electrical myostimulation and conventional aerobic
      exercise training in patients with chronic heart failure.
AB  - BACKGROUND: Physical training is recommended as an efficient therapy in patients
      with chronic heart failure (CHF). Low-frequency electrical myostimulation (EMS)
      has recently been suggested as a good alternative to conventional aerobic
      training. The aim of this study was to compare the effects of EMS and
      conventional exercise training in patients with moderate to severe CHF. METHODS:
      Twenty-four patients with stable CHF (56.7+/-7.3 years, New York Heart
      Association grades II and III) underwent 5 weeks of exercise training, 5 h a
      week, using EMS (n=12) or conventional (n=12) training programmes. At baseline
      and after the training period, patients performed a symptom-limited
      cardiopulmonary test, a 6-min and a 200-m walk exercises and an evaluation of
      maximal knee extensor strength. RESULTS: Oxygen uptake (VO2) and workload at the
      end of exercise (peak values) and at ventilatory threshold increased after EMS
      (P< or =0.05) and conventional exercise (P<0.05) training programmes. The slope
      of the relationship between VO2 and workload was reduced after EMS (P<0.05). The
      time to recover half of peak VO2 decreased irrespective of the training programme
      (P<0.001). EMS and conventional exercise training programmes also increased the
      maximal knee extensor strength (P<0.05), the distance walked in 6 min (P<0.01)
      and decreased the time elapsed to cover 200 m (P<0.05). These improvements were
      not statistically different between EMS and conventional exercise. CONCLUSION: In
      patients with moderate to severe CHF, 5 weeks of EMS and conventional exercise
      training produce similar improvements to exercise capacity and muscle
      performance.

PMID- 15942421
TI  - Moving towards non-moving training in chronic heart failure: is electrical
      stimulation a surrogate for exercise in reversing skeletal muscle abnormalities?

PMID- 15942422
TI  - Lifestyle, social class, and obesity-the Copenhagen Male Study.
AB  - OBJECTIVE: With the implicit purpose of identifying relevant intervention
      targets, the aim of the study was to test if lifestyle factors associated with
      obesity are unevenly distributed across social groups, and whether an uneven
      distribution of such factors may contribute to the explanation of social
      differences in obesity. DESIGN: Cross-sectional study of 3290 men aged 53-75
      years (mean=63) carried out in 1985-1986 using in addition, data from a previous
      baseline established in 1970-1971. Information about lifestyle factors was
      obtained from a questionnaire validated during an interview. Potential risk
      factors were smoking history, alcohol consumption, leisure time physical activity
      (LTPA), and from the 1985-1986 study only: consumption of tea and coffee, use of
      sugar in tea or coffee, and avoidance of fat in foods. The clinical examination
      included measurements of height and weight. Obesity was defined as a body mass
      index > or =30 (BMI=kg/m2). Based on information about education and job profile
      the men were subdivided into five social classes. RESULTS: Overall, 291 men
      (8.8%) were obese. The lower the social class the higher the proportion of obese
      men: in social classes I and II, 4.5% (of 953), social class III, 9.1% (of 636),
      social class IV, 11.1% (of 1353), and social class V, 11.6% (of 346), P<0.001
      (trend test). Leisure time physical activity, alcohol consumption, smoking
      habits, use of sugar in hot beverages, and consumption of coffee and tea, were
      all significantly associated with obesity, either positively or negatively, and
      even significantly associated with social class. Based on these lifestyle factors
      it was possible to discriminate subgroups with highly different prevalences of
      obesity. Despite this, adjustment for identified obesity covariates in a multiple
      logistic regression analysis did in no way explain the association of social
      class with obesity. CONCLUSION: Lifestyle factors in concert strongly associated
      with obesity are unevenly distributed across social classes, yet incapable of
      explaining the higher prevalence of obesity in lower social classes.

PMID- 15942423
TI  - Adherence to antihypertensive treatment: a critical factor for blood pressure
      control.
AB  - BACKGROUND: To compare rates of blood pressure (BP) control with the level of
      adherence to antihypertensive treatment and factors influencing compliance in
      Greek patients. DESIGN: An observational cross-sectional study on 1000
      consecutively treated hypertensive patients, admitted to a University department
      of general surgery in a Greek hospital. METHODS: Patients were interviewed by the
      same doctor using pre-coded questionnaires with questions on demographic data,
      health and treatment status. Blood pressure was measured using a standard mercury
      sphygmomanometer. Treatment of hypertension was defined as current use of
      antihypertensive medication. Compliance was defined as an affirmative reply to a
      number of questions regarding regular use of antihypertensive medication
      according to the physician's instructions. RESULTS: Satisfactory BP control
      (levels <140/90 mmHg) was documented in only 20% of the treated hypertensives.
      Compliance to antihypertensive treatment was found in only 15% of the patients.
      Control of BP was positively associated with compliance. Compliance was more
      common among patients aged <60, city dwellers, the better educated, those more
      adequately counselled by their physicians and those followed by a private doctor.
      As regards treatment, compliance was better among those taking one
      antihypertensive tablet per day, those who had never changed their
      antihypertensive regimen and those who had never changed their doctor.
      CONCLUSIONS: Compliance is associated with more effective BP control. Physicians
      can enhance patient compliance and hypertension control by devoting more time to
      counselling, avoiding unnecessary changes in drug regimens and restricting the
      tablet numbers.

PMID- 15942424
TI  - Which patients have the highest cardiovascular risk? A follow-up study from
      Turkey.
AB  - BACKGROUND: Recent guidelines target individuals at highest risk as a priority.
      However, implementation of guidelines even in this group is sub-optimal. DESIGN:
      A multicenter, observational follow-up study. METHODS: A total of 5600
      consecutive patients > or =55 year with high risk of vascular events were
      evaluated for risk factors and medication usage and followed for 1 year for
      primary end-points (death, myocardial infarction, stroke), and secondary end
      points (revascularization, hospitalization). RESULTS: The patients were divided
      into two groups: those without and with vascular disease. In the first group,
      mortality at 1 year was significantly higher in those with end organ damage (5.8
      versus 2.7%, P=0.005). Similarly, the mortality in patients with known vascular
      disease (CAD, peripheral vascular disease, ischaemic stroke) was higher in the
      presence of a previous vascular event (7.8 versus 5.3%, P=0.055, vascular event:
      non-fatal MI/stroke). The use of antiplatelets, statins, beta-blockers and
      angiotensin-converting enzyme inhibitors was low and did not improve in the
      follow-up period. The most important predictors of cardiovascular mortality were
      the presence of end organ damage [odds ratio (OR) 1.65, P=0.001], pre-existing
      vascular disease (OR 1.49, P=0.023) and protectively, the consistent use of
      angiotensin-converting enzyme inhibitors (OR 0.49, P=0.001). CONCLUSION: In a
      high-risk Turkish population, the early mortality and morbidity due to
      cardiovascular events was unacceptably high and medical treatment inadequate. The
      presence of end organ damage and a previous vascular event increased the risk
      even further and should be vigorously questioned. Aggressive lifestyle
      modification and medical therapy should be instituted in these patients.

PMID- 15942425
TI  - Standardization of total cholesterol measurement in population surveys--pre
      analytic sources of variation and their effect on the prevalence of
      hypercholesterolaemia.
AB  - BACKGROUND: The estimation of population distribution of total cholesterol, as
      well as other blood lipids requires population surveys. Comparability of the
      estimates over time or between populations requires a predefined, standardized
      measurement protocol. This paper will assess the effect of variation in the pre
      analytic procedures, on the estimation of population distribution of total
      cholesterol and the prevalence of hypercholesterolaemia. Implications of
      variation to real survey results are demonstrated on data collected during the
      WHO MONICA Project. DESIGN AND METHODS: The extent (%) of pre-analytic variations
      were determined by literature review. Simulations were then used to estimate the
      effect of these variations on the distribution of total cholesterol values. Three
      populations were selected as examples for different population distributions of
      total cholesterol levels and variations resulting from seasonal and postural
      changes, use of tourniquet, and serum versus plasma collection were simulated
      both individually and in combinations. RESULTS: Depending on the population
      distribution of total cholesterol, differences in pre-analytic procedures can
      explain a difference of up to 1.12 mmol/l in the mean total cholesterol between
      populations, and a difference up to 41% in the prevalence of
      hypercholesterolaemia (> or =6.5 mmol/l). CONCLUSIONS: Variation in results on
      measured total cholesterol levels due to differences in procedures during the pre
      analytic stage can diminish substantially the reliability and comparability of
      measurements among surveys over time and between populations. The effect of pre
      analytic variation in the population estimates of total cholesterol can be
      extensively reduced by standardization and training.

PMID- 15942426
TI  - Smoking, apolipoprotein E genotype, and early onset of coronary heart disease.
AB  - BACKGROUND: We examined the association between smoking, apolipoprotein E (ApoE)
      genotype, and early onset of coronary heart disease (CHD). DESIGN AND METHODS:
      Smoking behaviour and ApoE genotype of 904 patients with CHD aged 30-70 years
      were assessed with respect to age at onset of CHD. RESULTS: The adjusted odds
      ratio for early onset of CHD (< or =55 years) was 1.86 (95% confidence interval,
      1.31-2.62) for smokers compared to non-smokers. The ApoE genotype had no
      significant influence and there was no significant interaction between ApoE
      genotype and smoking. CONCLUSION: We found smoking but not ApoE genotype to be an
      independent risk factor for early onset of CHD.

PMID- 15942427
TI  - The influence of socio-economic status on casual blood pressures of the adult
      Nigerians.
AB  - BACKGROUND: Studies into social inequalities in health tend to focus more on
      parental socio-economic status (SES) as it affects the children. We aimed to test
      the hypothesis that socio-economic inequalities would not affect the casual blood
      pressure among Nigerian adults. METHODS AND RESULTS: Resting blood pressure (BP)
      and pulse rate of 1067 sedentary adults were measured. Rate pressure product and
      pulse pressure were later calculated. Second, a structured questionnaire, which
      objectively assessed the SES of the subjects, was administered. Subsequently, a
      self-rating SES ladder was employed to classify the subjects into different socio
      economic groups. This was used as a check for the structured questionnaire. A
      Pearson product correlation coefficient comparing the two outcome measures
      revealed a high correlation (r=0.951, P<0.01). Socio-economic status was found to
      have an inverse significant (P<0.05) effect on systolic pressure, heart rate and
      pulse pressure. The 95th centile blood pressure obtained was 154/91 mmHg.
      CONCLUSION: Low SES is associated with development of hypertension among the
      Nigerian adults.

PMID- 15942431
TI  - Herbal remedies in gastroenterology.
AB  - Complementary and alternative medicine (CAM) is presently not considered to be
      part of conventional medicine. Nevertheless, an estimated 51% of patients with
      gastrointestinal disorders have tried some from of CAM. Indeed, 10% of
      alternative medicines are being used for digestive symptoms. After prayer or
      spiritual healing, herbal medicine is the second most common CAM therapy. While
      herbal products make numerous health-related claims, those that have been
      systematically evaluated are unfortunately few. The modern gastroenterologist
      must be up to date with the regulations, side effects, and possible benefits of
      specific herbal products used in patients with gastrointestinal disorders.

PMID- 15942432
TI  - Probiotics used in human studies.
AB  - GOAL: To investigate the literature from 1980 to 2004 for the types of studies
      and organisms used as probiotics in human studies and diseases. METHODS: PubMed
      search for probiotic organisms used in studies from 1980 to August 2004. The data
      from those papers were evaluated for organisms used, dose, vehicle, frequency,
      and investigator's report of positive or negative results. RESULTS: A total of
      185 manuscripts were identified. Investigators reported results of both single
      and multiple organisms in the same manuscript. A single organism was used in 125
      reports, and multiple organisms, ranging from 2 to 9, were used in 60 reports.
      Positive results were reported in 239 clinical situations and negative results
      reported in 49 in a total of 288 clinical conclusions drawn by the respective
      investigators. The studies are tabulated in this review. CONCLUSION: There is a
      large literature available in credible journals that report benefit of probiotic
      administration using a wide range of doses, organisms, and clinical situations.
      Most of the studies are simple reports of a clinical situation and require
      additional evaluation.

PMID- 15942433
TI  - Probiotics for the developing world.
AB  - Every minute of every day more and more children die of diarrheal diseases and
      women, and girls become infected by HIV. An estimated 7,000 women become infected
      each day. While many valiant efforts are being made to address these issues,
      until now they have proved to be markedly ineffective. The notion that lactic
      acid bacteria, formulated into food or dietary supplements, could have a role to
      play in slowing the morbidity and mortality associated with HIV/AIDS and
      gastroenteritis, is built upon sound clinical findings and scientific
      investigations, yet no international efforts have been placed in this approach,
      to date. We hereby summarize the reasons why such efforts should be made, provide
      an example of one model being set up in sub-Saharan Africa, and challenge the
      international community to consider the potential benefits of probiotics,
      especially for communities not reached by governmental and nongovernmental
      agencies.

PMID- 15942434
TI  - Age, specialty, and practice setting predict gastroesophageal reflux disease
      prescribing behavior.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) affects more than 40% of
      adults in the United States each month. Although the economic costs of treating
      this disorder are enormous, the attitudes and prescribing preferences of
      physicians who treat patients with GERD are not well known. This study was
      undertaken to determine physician prescribing practices in the treatment of GERD.
      METHODS: A questionnaire was mailed to 687 randomly selected, practicing
      gastroenterologists, internists, and family physicians in the State of Maryland.
      Each questionnaire was identical and contained 7 questions designed to elicit
      demographic data (age, sex, degree, specialty, practice setting, years in
      practice, community served), and 16 questions related to the evaluation and
      treatment of GERD. RESULTS: A total of 214 completed questionnaires were returned
      (31.1%), nearly equally distributed among the three different specialty groups. A
      total of 82% of the respondents were male; 60% of the respondents had practiced
      more than 15 years, and 6% had practiced 4 years or less. Older physicians
      prescribed proton pump inhibitors more often than younger physicians for mild or
      intermittent GERD symptoms. Physicians in an academic setting were more likely to
      use step-down therapy in patients with well-controlled GERD symptoms than were
      HMO-employed physicians. Family physicians requested a barium swallow in the
      evaluation of uncomplicated GERD more frequently than did gastroenterologists or
      internists. Gastroenterologists were more likely than family physicians and
      internists to recommend upper endoscopy for GERD patients with warning symptoms
      and for patients with long-standing reflux disease. CONCLUSIONS: Age, specialty,
      number of years in practice, and practice setting significantly influence how
      physicians evaluate and treat patients with GERD. Educational efforts to improve
      the evaluation and treatment of patients with GERD may require different
      strategies for different types of healthcare providers.

PMID- 15942435
TI  - Clinical outcomes and prognostic factors for patients with early esophageal
      squamous cell carcinoma treated with definitive radiation therapy alone.
AB  - GOALS AND BACKGROUND: There are great differences between treatment methods for
      early-stage esophageal cancer in institutions. Radiation therapy has been
      considered to be an effective modality as organ-preserving treatment of the
      disease. The aim of this study is to assess the effect and limitation of
      radiation therapy on patients with early esophageal cancer. STUDY: The subjects
      were 38 patients with stage I (T1N0M0) squamous cell carcinoma of the esophagus
      who had received definitive radiation therapy alone. Eleven tumors were assessed
      within the mucosal layer, whereas 27 tumors showed submucosal invasion by
      examination using endoscopic ultrasound. All patients were treated with more than
      60 Gy using a conventional daily fractionation dose at 2 Gy. An additional boost
      with brachytherapy was performed for 20 patients, and the prescribed doses were
      10 Gy (5 Gy x 2 times) with low dose rate (8 patients) and 9 Gy (3 Gy x 3 times)
      with high dose rate (12 patients). Outcomes and prognostic factors, including the
      efficacy of intraluminal brachytherapy, were investigated. RESULTS: The cause
      specific survival rate and the local control rate at 5 years were 82.6% and
      86.3%, respectively. Recurrences were noted in 8 patients with submucosal cancer,
      but no recurrence was observed in patients with mucosal cancer. In the present
      study, tumor length was a statistically significant prognostic factor for cause
      specific survival (P = 0.018) and tumor depth tended toward statistical
      significance (P = 0.073). In 27 patients with submucosal cancer, the tumor length
      was also statistically significant for the survival (P = 0.032). The 5-year cause
      specific survival rates for the short tumor group and the long tumor group were
      85.7% and 55.6%, respectively. On the other hand, the use of intraluminal
      brachytherapy had no significant effect on patient survival. CONCLUSION:
      Radiation therapy is very effective for early esophageal squamous cell carcinoma
      with tumor length less than 5 cm, but other treatment modalities, including
      chemoradiotherapy especially for inoperable patients, should be considered for
      submucosal cancer with a tumor length of 5 cm or more.

PMID- 15942436
TI  - A survey of credentialing practices of gastrointestinal endoscopy centers in the
      United States.
AB  - BACKGROUND: Competence in gastrointestinal (GI) endoscopy correlates with the
      number of procedures performed by the endoscopist. For each GI endoscopic
      procedure, the American Society for Gastrointestinal Endoscopy (ASGE) guidelines
      recommend minimum numbers needed to assess competence. METHODS: We conducted an
      anonymous mail survey to determine whether GI endoscopy centers in the United
      States follow ASGE or other guidelines for granting and renewing endoscopic
      privileges. RESULTS: Completed surveys were received from 479 respondents in 46
      states, Puerto Rico, and the District of Columbia. Most respondents were either
      the physician director (24%) or nurse manager (57%) of the endoscopy center. Most
      centers have more than 5 endoscopists (62%), and gastroenterologists performed
      procedures in the majority of the centers (89%). For initial endoscopic
      credentialing, few centers require a minimum number of procedures and only 10%
      meet ASGE criteria. To maintain credentials, less than one third require a
      minimum number and only 2% require more than 25 procedures/year. Although three
      fourths report periodic review of procedures, less than 5% review them more
      frequently than every 6 months. Only 20% of centers had ever denied endoscopic
      privileges (poor skills [80%], no references [27%], poor communication [7%], and
      excess complications [6%]) for which half faced litigation. CONCLUSIONS: Most GI
      endoscopy centers responding to this survey have no minimum standards for
      determining endoscopic competence and may credential GI endoscopists with
      suboptimal training. Only 10% adhere to ASGE guidelines. Moreover, there is lack
      of uniformity to application of these guidelines, and few centers use resulting
      data to deny or renew credentials. To guarantee high-quality endoscopic practice,
      more stringent, universal credentialing standards are required.

PMID- 15942437
TI  - The prevalence of unrecognized adult celiac disease in Central Anatolia.
AB  - BACKGROUND: The aim of this study is to assess the prevalence of unrecognized
      adult celiac disease in Central Anatolia of Turkey and establish if prevalence
      figures are similar to other reports in the international literature. METHODS:
      Subjects were randomly selected from patients at the time of blood sampling
      because of a routine examination or suspicion of some disorder other than celiac
      diseases and were screened with anti-tissue transglutaminase IgA and serum IgA
      measurements. Duodenal biopsies were taken from the patients who were found
      positive for anti-tissue transglutaminase IgA and had low IgA levels. RESULTS: A
      total of 906 subjects between 20 and 59 years of age were included. Small bowel
      biopsies were performed for 55 of the 906 participants. Fifty-two of 55
      participants taken biopsies had anti-tissue transglutaminase IgA levels greater
      than 15 IU/mL and 3 of them had low IgA levels. Celiac disease was diagnosed as 9
      of 906 (0.99%). The majority of the patients with celiac disease had nonspecific
      gastrointestinal symptoms. There was no correlation between the titers of anti
      tissue transglutaminase IgA and the severity of histopathologic findings.
      CONCLUSIONS: In this study, we found that unrecognized adult celiac disease in
      Central Anatolia affects approximately 1% of the population, and the major
      constellation of symptoms are nonspecific gastrointestinal related. Serologic
      data are not adequate for a definite diagnosis, but the anti-tissue
      transglutaminase IgA test has high diagnostic value and may be used as screening
      tool. Confirmation with intestinal biopsy is required for a definite diagnosis.

PMID- 15942438
TI  - Breath methane associated with slow colonic transit time in children with chronic
      constipation.
AB  - OBJECTIVE: This study analyzed the relationship between methane production and
      colonic transit time in children with chronic constipation. METHODOLOGY: Forty
      children, from 3 to 13 years of age, suffering from chronic constipation were
      included. Methane production was defined when the breath methane concentration
      was greater than 3 ppm. The total and segmental colonic transit times were
      measured with radio-opaque markers. RESULTS: Soiling was present in 34 (85.0%) of
      40 patients with constipation. Methane production was present in 25 of 34 (73.5%)
      patients with constipation and soiling and only in 1 (16.7%) of 6 with
      constipation but without soiling (P = 0.014). The medians of total colonic
      transit time were 80.5 and 61.0 hours, respectively (P = 0.04), in methane and
      nonmethane producers. Segmental colonic transit times were 17.5 and 10.5 hours,
      respectively (P = 0.580), in right colon, 29.5 and 10.5 hours (P = 0.001),
      respectively, in left colon, and 31.5 and 27.0 hours (P = 0.202), respectively,
      in the rectosigmoid. By the sixth week of treatment, the reduction in the total
      colonic transit time was greater in patients who had become nonmethane producers.
      CONCLUSION: The presence of breath methane in children with chronic constipation
      may suggest the possibility of prolonged colonic transit time.

PMID- 15942439
TI  - Preprocedure patient values regarding sedation for colonoscopy.
AB  - BACKGROUND: Adherence rates for screening colonoscopy remain low. There are
      little data describing pre-colonoscopy patient concepts, values, and preferences
      for sedation during colonoscopy. In this study, we sought to investigate
      preprocedure patient values regarding sedation use for colonoscopy. METHODS:
      Questionnaires were administered to 210 consecutive outpatients presenting for
      colonoscopy. An unscaled visual analog scale was used to value each of eight
      statements relating to sedation. RESULTS: The statement receiving the highest
      valuation was "I don't want to feel any pain" (mean score, 82 +/- 21), followed
      by "I want to go to sleep and not wake up until the procedure is over" (mean
      score, 71 +/- 31), and "I want to be alert as soon as possible after the
      procedure" (mean score, 65 +/- 30). The statement receiving the lowest value was
      "I'd like to watch as much of the procedure as I can" (22 +/- 29). Patients who
      preferred to undergo colonoscopy without sedation were more likely to be men (P =
      0.001) and more likely to have graduate or professional educational degrees (P <
      0.001). CONCLUSIONS: Our data suggest that, on average, American patients place
      the highest valuation on experiencing no pain during colonoscopy, waking up
      promptly after the procedure, and for going to sleep and not waking up until the
      procedure is over. However, unsedated colonoscopy does appeal to a small minority
      of patients, primarily men with graduate educations.

PMID- 15942440
TI  - A review of Silybum marianum (milk thistle) as a treatment for alcoholic liver
      disease.
AB  - Silybum marianum (milk thistle) and its derivatives have been used for centuries
      for the treatment of liver disease. This review focuses exclusively on published
      literature pertaining to the potential use of Silybum marianum or its derivatives
      for the treatment of alcoholic liver disease. Clinical studies have varied
      greatly in quality, with the majority limited by inadequate sample size, lack of
      uniformity in the population treated, lack of standardization of preparations
      studied, variability in dosing regimens, inconsistent outcome measures, and lack
      of information on concurrent use of alcohol during the treatment period. While
      Silybum marianum and its derivatives appear to be safe and the available evidence
      on the mechanisms of action appears promising, there are currently insufficient
      data from well-conducted clinical trials to recommend their use in patients with
      alcoholic liver disease.

PMID- 15942441
TI  - Diagnosis of liver cirrhosis: a comparison of modified ultrasound and laparoscopy
      in 100 consecutive patients.
AB  - BACKGROUND/GOALS: Liver cirrhosis, the final stage of chronic liver disease, is
      characterized by an unfavorable prognosis and an increased risk of hepatocellular
      carcinoma and also requires an appropriate management. Laparoscopy, the gold
      standard in the diagnosis of cirrhosis, is hampered by its invasiveness.
      Therefore, a noninvasive method for diagnosing liver cirrhosis would be of great
      benefit. STUDY: A consecutive series of 100 patients, sent to our
      gastroenterological unit for diagnostic laparoscopy, underwent a standardized
      ultrasonographic examination prior to laparoscopy. RESULTS: Conventional
      ultrasonographic examination revealed a sensitivity of 55% and a specificity of
      86% in the diagnosis of cirrhosis. Considering the assessment of the transmission
      of heart pulsation on the liver surface, the corresponding values improved by
      increasing to 85% and 93%. CONCLUSION: Evaluating the transmission of heart
      pulsation on the liver surface improves the ability of ultrasound to diagnose
      liver cirrhosis; therefore, it should be an integral part of routine sonographic
      examination of the liver.

PMID- 15942442
TI  - Better survival in female patients with hepatocellular carcinoma: oral
      contraceptive pills related?
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) has an indisputable male predominance.
      "Gender" as an independent prognostic factor for survival is, however,
      controversial. GOALS: Determine the influence of gender on survival in HCC
      patients, and identify factors that may account for the difference. METHODS: A
      retrospective analysis on a prospectively collected database in a 15-year period,
      from 1989 to 2003. RESULTS: A total of 3,171 HCC patients were managed in our
      institution (946 with curative treatment, 1,388 with palliative treatment, and
      837 with supportive treatment) and studied. Female patients (n = 520) were 4.3
      years older (P = 0.000), had a lower proportion of smokers and drinkers (P =
      0.000), and were less likely to be hepatitis B carriers (P = 0.000). There was no
      difference in Child-Pugh status, tumor size, and the use of different treatments
      between genders. The overall median survival was 25.7 months longer in females
      after curative treatment (73.6 vs. 47.9 months; P = 0.012). The survival benefit
      in female patients was observed in early-stage diseases and persisted when only
      hepatitis B surface antigen-positive patients were analyzed (96.4 vs. 47.9
      months; P = 0.044). With multivariate analysis, gender, indocyanine green test
      value at 15 minutes, number of tumor nodules, size of tumor, major vascular
      invasion, invasion of adjacent organs, and tumor rupture were the independent
      variables for survival. More importantly, in female patients, history of using
      oral contraceptive was an independent factor with survival benefit (P = 0.004).
      CONCLUSION: Gender is an independent variable for survival after curative
      treatment of HCC. A survival benefit was observed in females. History of using
      oral contraceptive is associated with a better long-term survival in female
      patients.

PMID- 15942443
TI  - Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in
      chronic liver diseases.
AB  - OBJECTIVES: To evaluate whether chronic therapy with probiotics affects plasma
      levels of cytokines and oxidative/nitrosative stress parameters, as well as liver
      damage, in patients with various types of chronic liver disease. PATIENTS AND
      METHODS: A total of 22 nonalcoholic fatty liver disease (NAFLD) and 20 alcoholic
      liver cirrhosis (AC) patients were enrolled in the study and compared with 36 HCV
      positive patients with chronic hepatitis without (20, CH) or with (16, CC) liver
      cirrhosis. All patients were treated with the probiotic VSL#3. Routine liver
      tests, plasma levels of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)
      6 and -10, malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE), S-nitrosothiols
      (S-NO), were evaluated on days -30, 0, 90, and 120. RESULTS: Treatment with VSL#3
      exerted different effects in the various groups of patients: in NAFLD and AC
      groups, it significantly improved plasma levels of MDA and 4-HNE, whereas
      cytokines (TNF-alpha, IL-6, and IL-10) improved only in AC patients. No such
      effects were observed in HCV patients. Routine liver damage tests and plasma S-NO
      levels were improved at the end of treatment in all groups. CONCLUSIONS: Results
      of the study suggest that manipulation of intestinal flora should be taken into
      consideration as possible adjunctive therapy in some types of chronic liver
      disease.

PMID- 15942444
TI  - A clinicopathologic study of primary adenosquamous carcinoma of the liver.
AB  - BACKGROUND: Adenosquamous carcinoma (ASC) is a rare tumor of the liver, which
      carries a poor prognosis. In this study, we reviewed reported cases of ASC and
      examined their clinicopathologic features. MATERIALS AND METHODS: A computer
      MEDLINE search found 65 histologically defined primary ASC cases reported in the
      literature from 1975 to 2003, including our case. Of these, detailed data were
      obtained for 42 cases, and these were subsequently investigated
      clinicopathologically. RESULTS: Among the 42 cases, 34 were reported to have died
      of ASC and 5 cases were alive at the time of the study. The mean survival of
      these 34 cases was 8.7 months. Multivariate analysis revealed that lymph node
      metastasis and the elevation of total bilirubin were associated with poor
      survival after surgery, and lymph node metastasis, intrahepatic metastasis,
      location of tumor in the right lobe, and the pathologic stage were significant
      factors for all cases. CONCLUSION: The current study highlights the prognostic
      factors of ASC of the liver, showing that the prognosis for patients with ASC is
      poor.

PMID- 15942445
TI  - Dropped clip endoscope obstruction: recognition and management.

PMID- 15942446
TI  - Pneumatic dilation for the treatment of achalasia in untreated patients and
      patients with failed Heller myotomy.

PMID- 15942447
TI  - Roux stasis syndrome: clinical improvement with Tegaserod.

PMID- 15942449
TI  - A forkhead in the road to longevity: the molecular basis of lifespan becomes
      clearer.
AB  - OBJECTIVE: Although the quest for longevity is as old as civilization itself,
      only recently have technical and conceptual advances in genomics research brought
      us to the point of understanding the precise molecular events that make us age.
      This heralds an era when manipulations of these will enable us to live longer,
      healthier lives. The present review describes how recent experimental strategies
      have identified key genes and intracellular pathways that are responsible for
      ageing and longevity. FINDINGS: In diverse species transcription factors
      belonging to the forkhead/winged helix box gene, group O (FOXO) subfamily have
      been found to be crucial in downstream suppression of the life-shortening effects
      of insulin/insulin-like growth factor-I receptor signalling pathways that, when
      upregulated, accelerate ageing by suppression of FOXO. The various adverse
      processes activated upon FOXO suppression include increased generation of
      reactive oxygen species (ROS). ROS are pivotal for the onset of various common
      conditions, including hypertension, atherosclerosis, type 2 diabetes, cancer and
      Alzheimer's disease, each of which shortens lifespan. In humans, FOXO3a, as well
      as FOXO1 and -4, and their downstream effectors, could hold the key to
      counteracting ageing and common diseases. An understanding of the processes
      controlled by these FOXOs should permit development of novel classes of agents
      that will more directly counteract or prevent the damage associated with diverse
      life-threatening conditions, and so foster a life of good health to a ripe old
      age. Just like caloric restriction, lifespan can be increased in various species
      by plant-derived polyphenols, such as resveratrol, via activation of sirtuins in
      cells. Sirtuins, such as SIRT1 in mammals, utilize FOXO and other pathways to
      achieve their beneficial effects on health and lifespan. CONCLUSION: Lifespan is
      tractable and basic mechanisms are now known. Longevity research complements and
      overlaps research in most major medical disciplines. Current progress bodes well
      for an ever-increasing length of healthy life for those who adapt emerging
      knowledge personally (so-called 'longevitarians').

PMID- 15942450
TI  - Pharmacogenomics of blood pressure response to antihypertensive treatment.
AB  - PURPOSE IDENTIFICATION: Inter-individual variability in blood pressure response
      to treatment is well documented, but a clinically useful means to distinguish
      responders from non-responders has been elusive. With the advent of new
      technologies and genomic knowledge, more investigators are seeking to identify
      genetic determinants of blood pressure response to therapy. STUDY SELECTION: We
      identified studies of candidate polymorphisms from an initial PubMed search using
      the MESH terms 'Hypertension: Drug Therapy' and 'Genetics' or 'Pharmacogenetics',
      limiting results to English-language publications on studies in human adults. We
      further identified specific polymorphisms of interest noted in earlier reviews
      and performed additional PubMed searches based on these candidate genes.
      Pertinent studies were further extracted from the references of studies already
      identified. We focused on clinical trials that measured blood pressure response
      to a medication or class of medications over a minimum of 4 weeks. DATA
      EXTRACTION: We evaluated studies looking at blood pressure response to commonly
      used classes of antihypertensive medications by major genetic variants. RESULTS
      OF ANALYSIS: Although many studies show that blood pressure response to a given
      class of antihypertensive medications varies by genotype for different
      polymorphisms, none of the genotypes identified consistently predicted blood
      pressure response. CONCLUSIONS: Common variants may influence response to
      diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and
      angiotensin receptor blockers, but studies of polymorphisms have generally
      yielded conflicting results. The inclusion of pharmacogenomic studies in large
      clinical trials and other more innovative investigative methods may provide
      greater clarity of the potential role for genotyping in the treatment of patients
      with hypertension.

PMID- 15942451
TI  - Pharmacogenomics in hypertension: present practicalities and future potential.

PMID- 15942452
TI  - The question of the role of ethnicity on cardiovascular risk: does it matter
      where we come from?

PMID- 15942453
TI  - Correction of endothelial dysfunction by tetrahydrobiopterin: new hope for the
      treatment of arterial hypertension?

PMID- 15942454
TI  - Arterial pulse waveforms: defined at birth or barking up the wrong arterial tree?

PMID- 15942455
TI  - Prevalence and therapeutic control of hypertension in French Caribbean regions.
AB  - OBJECTIVE: To describe characteristics of hypertension in French Caribbean
      regions. DESIGN: A cross-sectional worksite study. SETTING AND PARTICIPANTS: A
      random sample of 6136 workers referred for annual check-up from Martinique,
      French Guyana and Guadeloupe. An average of three consecutive measurements was
      taken as the blood pressure (BP) level. An additional visit was required in
      subjects not taking antihypertensive medications with an average BP over 140/90
      mmHg. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hypertension prevalence,
      awareness, treatment and control. RESULTS: The age-specific prevalence of
      hypertension, based on two visits, increased from 3.2% in men below 30 years to
      46.9% in those older than 50 years. The corresponding values found in women were
      1.8 and 42.6%. The overall prevalence was 19.5% in men and 18.9% in women. The
      rate of awareness remained low while age increased. The use of antihypertensive
      medications slowly increased with age, but overall the rate remained lower in men
      compared with women. Up to 71% of hypertensive women received antihypertensive
      medications. Compared with previous studies, a high proportion of adequately
      treated patients was found among women (44.9%). Only 30.4% of hypertensive men
      were treated, and as a result the control rate was lower (13.3%). CONCLUSION:
      Major sex-related differences are found in the control of high BP, with an
      unexpected high rate observed among Caribbean women. Better awareness and higher
      treatment rates play an important role in explaining such results. This may be
      important, especially in developing countries, where poor control of hypertension
      is a major cause of cardiovascular diseases.

PMID- 15942456
TI  - Ethnic differences in cardiovascular and all-cause mortality in Birmingham,
      England: the Birmingham Factory Screening Project.
AB  - OBJECTIVES: To compare cardiovascular and all-cause mortality, among white
      Europeans, African-Caribbeans and South-Asians, in relation to baseline
      demographic characteristics and blood pressure variables. DESIGN: Observational
      follow-up study. SETTING: Community settings in Birmingham, UK. PARTICIPANTS: Two
      thousand and eighty-nine white European and 340 African-Caribbean men and women,
      and 195 South-Asian men whose survival status on 31 December 2003 was known.
      INTERVENTIONS: Follow-up for assessment of all-cause and cardiovascular mortality
      over a mean (SD) 20.3 (4.2) years. MAIN OUTCOME MEASURES: All-cause and
      cardiovascular mortality. RESULTS: There were no significant ethnic differences
      in all-cause or cardiovascular mortality for men [adjusted hazard ratio (HR) =
      1.02; 95% confidence interval (CI), 0.80-1.28 and HR = 1.33; 95% CI, 0.99-1.79,
      respectively] or women (adjusted HR = 0.61; 95% CI, 0.29-1.32 and HR = 1.19; 95%
      CI, 0.41-3.45, respectively) in either univariate or multivariate analyses. The
      only independent predictors of both all-cause and cardiovascular mortality were
      age, sex, smoking and mean systolic blood pressure or hypertension. CONCLUSIONS:
      It appears that ethnicity per se is not an independent risk factor for all-cause
      and cardiovascular mortality between white Europeans and African-Caribbeans in
      the present study. The data concerning ethnic differences in all-cause and
      cardiovascular mortality for South-Asians is limited, given that significantly
      fewer South-Asian men could be traced by the Office for National Statistics
      (ONS), hence we do not know their survival status, and the total lack of data on
      South-Asian women.

PMID- 15942457
TI  - Prevalence and determinants of prehypertension status in the Taiwanese general
      population.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence rate of
      prehypertension and to compare the differences in demographic factors,
      anthropometric measurements, lifestyles and metabolic profiles between
      normotensive and prehypertensive individuals. DESIGN: Data were based on the
      Nutrition and Health Survey in Taiwan (NAHSIT), a cross-sectional survey that
      adopted a multi-stage, stratified clustering sampling scheme. The data collection
      period was from 1 January 1993 to 31 December 1996. METHODS: This study was a
      secondary analysis of data previously collected. Data from 1039 men and 1186
      women, aged 18-96 years, were analyzed. RESULTS: Approximately 34% of Taiwanese
      adults had prehypertension. The prevalence rate of prehypertension was higher
      among men (36%) than women (32%). In univariable logistic analysis, sex, age
      group, age, waist-hip ratio (WHR) group, body mass index (BMI) group, waist
      circumference, blood sugar, triglyceride, high-density lipoprotein cholesterol
      (HDL), low-density lipoprotein cholesterol (LDL), cholesterol/HDL and smoking
      status were significantly associated with prehypertension status. Multivariable
      logistic regression revealed that age [odds ratio (OR) = 1.014, 95% confidence
      interval (CI) = 1.004-1.0249] and BMI (OR = 1.106, 95% CI = 1.051-1.165) were the
      determinants of prehypertension status in men. For women, age (OR = 1.033, 95% CI
      = 1.022-1.044), waist circumference (OR = 1.031, 95% CI = 1.012-1.051) and
      triglyceride (OR = 1.003, 95% CI = 1.000-1.005) were the determinants of
      prehypertension. CONCLUSIONS: This study underscores the importance of general
      obesity and central obesity as risk factors for prehypertension in the Taiwanese
      adult population. These two indices of obesity have different impacts on men and
      women.

PMID- 15942458
TI  - Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and
      hypertension in a general population sample.
AB  - OBJECTIVE: The Glu298Asp (E/D) polymorphism of the endothelial nitric oxide
      synthase (eNOS) gene has been related to hypertension. Since several studies have
      produced contradictory results, this issue is still subject to ongoing debate. We
      investigated the association of the eNOS E298D polymorphism with hypertension and
      with blood pressure (BP) in a large population-based sample of Caucasian
      ethnicity. DESIGN: Cross-sectional study in a random sample of the general
      population. METHODS: The eNOS E298D polymorphism was determined by 5'-exonuclease
      assay among 4219 participants aged 20-79 years of the Study of Health in
      Pomerania (SHIP). RESULTS: The percentages of the EE298, ED298 and DD298
      genotypes were 49.2, 42.0 and 8.8%, respectively. The D allele frequencies did
      not differ between the groups of normotensive and hypertensive subjects (29.7
      versus 29.9%, P = 0.812). Similarly, no association could be established between
      E298D genotype and prevalent hypertension, neither for D allele carriership
      (multivariate odds ratio 0.97, 95% confidence interval 0.83-1.12) nor for DD
      homozygosity (multivariate odds ratio 1.10, 95% confidence interval 0.84-1.43).
      Likewise, genotype groups did not differ as to the distribution of systolic
      (ANCOVA P = 0.917) or diastolic BP values (ANCOVA P = 0.657). Nearly identical
      results were obtained if the analyses were repeated sex-specifically or if
      subjects on antihypertensive medication were excluded. CONCLUSION: In a
      population-based cohort of Caucasians covering a broad age range, the eNOS E298D
      polymorphism is neither associated with prevalent hypertension nor with systolic
      or diastolic BP. These results do not support the hypothesis that the E298D
      polymorphism contributes to the genetic susceptibility to hypertension.

PMID- 15942459
TI  - Genetic effects on blood pressure localized to chromosomes 6 and 7.
AB  - OBJECTIVE: To identify quantitative trait loci (QTL) contributing to the
      variation in blood pressure in a west African population. METHODS: We conducted a
      multi-stage genome scan in a population sample from rural Nigeria. A 10
      centimorgan genome-wide screen for log-transformed systolic blood pressure (SBP)
      and diastolic blood pressure (DBP) was first performed based on 1054 individuals
      from 188 families. In the second phase we performed a similar analysis in an
      independent sample of 621 individuals from 101 families. In a third follow-up
      fine mapping phase we genotyped 25 additional markers in the three regions
      identified in the first two phases. RESULTS: Genome-wide significant linkage
      evidence was found for SBP on chromosome 7p (lod = 4.73, genome wide P < or =
      0.01, point-wise P = 1.53 x 10) in the combined sample. Suggestive linkage
      evidence was also detected on 6q (lod = 2.9, point-wise P = 0.00013) and 7q (lod
      = 2.6, point-wise P = 0.00027) for SBP, and 7q (lod = 1.6, point-wise P = 0.003)
      for DBP. CONCLUSIONS: This study has identified several regions that may harbor
      genetic variants affecting the variation in blood pressure. Further association
      mapping under the linkage peaks will be required to refine the linkage evidence
      that has emerged from our analysis.

PMID- 15942460
TI  - Supplementation with tetrahydrobiopterin prevents the cardiovascular effects of
      angiotensin II-induced oxidative and nitrosative stress.
AB  - OBJECTIVE: The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a
      critical determinant of endothelial nitric oxide synthase (eNOS) activity. When
      BH4 availability is limited, eNOS does not produce nitric oxide (NO) but instead
      generates superoxide. BH4 may reverse endothelial dysfunction due to
      cardiovascular disease, including atherosclerosis, coronary artery disease and
      hypertension. In this study, the influence of BH4 on cardiovascular parameters
      and the production of free radicals following angiotensin II (Ang II) infusion
      was assessed. METHODS: BH4 (20 mg/kg per day in drinking water) was administered
      with Ang II (300 ng/kg per min subcutaneously, osmotic pump) for 7 days in
      Sprague-Dawley rats. In addition, BH4 was also given in vehicle-infused rats.
      RESULTS: Treatment with BH4 significantly prevented some of the effects of Ang
      II, such as impaired vascular responses to acetylcholine, hypertension and
      increases in heart weight index values. Treatment with BH4 also significantly
      reduced Ang II-induced increases in inducible NO synthase expression,
      nitrotyrosine immunostaining, NO production and superoxide anion formation in
      rats. CONCLUSION: These results indicate that BH4 might prevent the development
      of hypertension and myocardial hypertrophy, as well as the Ang II-induced
      production of superoxide and NO, thereby reducing the production of
      peroxynitrite. Therefore, BH4 may protect against the cardiovascular
      manifestations of oxidative and nitrosative stress in this experimental model of
      Ang II-mediated hypertension.

PMID- 15942462
TI  - Association of pulse waveform characteristics with birth weight in young adults.
AB  - OBJECTIVE: An association between birth weight and blood pressure has been
      reported in many studies, but the strength of this association has been disputed.
      Birth weight could, however, be associated with alterations in the proximal
      arterial tree that have little effect on blood pressure. The objective of this
      study was to examine the relationship between birth weight and characteristics of
      the proximal arterial tree determined by pulse wave analysis. METHODS: An
      optically derived digital volume pulse was used to obtain indices of pressure
      wave reflection (reflection index; RI) determined by characteristics of
      small/medium sized arteries and of large artery stiffness (stiffness index; SI)
      in healthy young adults (n = 220, 111 women, aged 16-26 years). Birth weight was
      obtained from maternal recall. RESULTS: Diastolic blood pressure was
      significantly correlated with birth weight (P < 0.001) but birth weight accounted
      for only 5% of the variance in diastolic blood pressure. RI was significantly
      correlated with birth weight in women (r = -0.33, P < 0.001) but not in men, and
      there was a significant interaction between birth weight and sex (P < 0.001). SI
      was significantly independently correlated with birth weight in both men and
      women (r = -0.41 and -0.49, each P < 0.0001) and birth weight accounted for 17%
      of the overall (men and women) variance in SI. CONCLUSIONS: These results suggest
      a close association between birth weight and characteristics of the arterial tree
      proximal to resistance vessels in young adults and a sex-specific association
      with characteristics influencing arterial pressure wave reflection.

PMID- 15942461
TI  - Effect of combination of calcium antagonist, azelnidipine, and AT1 receptor
      blocker, olmesartan, on atherosclerosis in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: Angiotensin II type 1 receptor blockers (ARB) are widely recognized to
      have a vasculoprotective effect. Accumulating data have revealed that calcium
      antagonists also retard atherosclerosis. We examined the possibility that
      combination therapy of ARB and calcium antagonists could more effectively prevent
      atherosclerosis than monotherapy. METHODS AND RESULTS: We observed a marked
      increase in the atherosclerotic area, associated with the exaggerated expression
      of nicotinamide adenine dinucleotide (phosphate), reduced form [NAD(P)H] oxidase
      subunits (p22 and p47) and superoxide anion production, in the aorta of
      apolipoprotein E-deficient mice maintained on a 1.25% high-cholesterol diet for
      10 weeks. A calcium antagonist, azelnidipine, at a dose of 1 mg/kg a day or an
      ARB, olmesartan, at a dose of 3 mg/kg a day, significantly inhibited these
      parameters, with no change in systolic blood pressure and the blood cholesterol
      level. Moreover, the co-administration of lower doses of azelnidipine (0.1 mg/kg
      a day) and olmesartan (1 mg/kg a day) significantly inhibited the atherosclerotic
      area and oxidative stress, whereas azelnidipine or olmesartan alone at these
      doses did not affect these parameters. Furthermore, we observed similar
      inhibitory effects of azelnidipine or olmesartan on angiotensin II-induced NADPH
      oxidase activity and Akt activity in cultured vascular smooth muscle cells.
      CONCLUSION: These results suggest that the co-administration of calcium
      antagonists and ARB synergistically blunts oxidative stress at least partly
      through the inhibition of Akt activity and enhances the beneficial effects of
      these drugs on atherosclerosis compared with monotherapy.

PMID- 15942463
TI  - Morphological changes rather than flow-mediated dilatation in the brachial artery
      are better indicators of the extent and severity of coronary artery disease.
AB  - OBJECTIVES: The aim of this study was to examine the relationship between
      morphological and functional parameters of the brachial and carotid arteries and
      the angiographic extent and severity of coronary artery stenosis in patients with
      severe coronary artery disease (CAD). DESIGN: A cross-sectional study. SETTING:
      University hospital. MAIN OUTCOME MEASURES: Flow-mediated dilatation (FMD),
      intima-media thickness (IMT) in the brachial artery and atherosclerotic wall
      changes in the carotid arteries were measured by B-mode high-resolution
      ultrasound in 58 patients who had undergone coronary angiography. RESULTS: A
      significant correlation was seen between the extent of coronary artery stenosis
      defined as the coronary angiographic score and both the mean brachial artery IMT
      and intima-media area (IMa; P = 0.01 and P = 0.04, respectively). There was no
      significant correlation between FMD and the extent of coronary artery stenosis. A
      significant correlation was seen between the mean carotid artery IMT and the mean
      brachial artery IMT (r = 0.30, P = 0.03). However, there was no significant
      correlation between FMD and the mean carotid artery IMT or IMa (r = 0.16, P =
      0.23 and r = 0.17, P = 0.24, respectively). CONCLUSIONS: Morphological but not
      functional parameters of the brachial artery are associated with the extent of
      coronary artery stenosis and atherosclerotic wall changes in the carotid arteries
      in patients with severe CAD. These findings indicate a potential of B-mode
      ultrasonography of morphological parameters in the brachial artery in the
      diagnostic and prognostic evaluation of patients with suspected CAD.

PMID- 15942464
TI  - Central obesity is associated with reduced peripheral wave reflection in
      Indigenous Australians irrespective of diabetes status.
AB  - OBJECTIVE: To determine the influence of central obesity and type 2 diabetes on
      peripheral wave reflection in Indigenous Australians. DESIGN AND METHODS: A cross
      sectional study of remote Indigenous Australians with (n = 43) and without (n =
      54) type 2 diabetes of similar age (47 years) and sex; using anthropometric and
      bioelectrical impedance measures of obesity and applanation tonometry to
      determine the aortic augmentation index (AI) as an index of peripheral wave
      reflection. RESULTS: Indices of obesity were significantly higher in the diabetic
      than non-diabetic participants [body mass index (BMI): 27.3 versus 24.6 kg/m, P =
      0.018; waist circumference: women 101 versus 94 cm, P = 0.008, men 102 versus 91
      cm, P = 0.039]. AI was negatively related to obesity: BMI (r = -0.35, P =
      0.0003), weight (r = -0.44, P < 0.0005), waist circumference (r = -0.34, P =
      0.0003) and fat mass (r = -0.35, P < 0.0005). There was no significant difference
      in AI between the groups with and without diabetes. On multiple regression
      analysis, 66% of the variance in AI was explained with the following significant
      predictors: age, heart rate, male gender, fat mass and mean arterial pressure.
      Similar results were obtained when weight, waist circumference or BMI were
      substituted for fat mass. CONCLUSION: When compared with Indigenous Australians
      without diabetes, those with type 2 diabetes do not have greater aortic pressure
      augmentation from peripheral wave reflection. However, obesity, irrespective of
      the index used, was related to lower peripheral wave reflection in both those
      with and without type 2 diabetes.

PMID- 15942465
TI  - Simultaneous echocardiography and myocardial perfusion single photon emission
      computed tomography associated with dobutamine stress to predict long-term
      cardiac mortality in normotensive and hypertensive patients.
AB  - BACKGROUND: Echocardiography and myocardial scintigraphy associated with
      dobutamine stress are used for assessing risk in coronary artery disease. We
      compared the accuracy of the two modalities applied simultaneously for predicting
      long-term cardiac mortality in normotensive and hypertensive patients. METHODS:
      Three hundred and fifty-one consecutive patients underwent dobutamine stress with
      simultaneous echocardiography and Tc-sestamibi single photon emission computed
      tomography (SPECT). Fifty patients underwent early (<60 days) revascularization
      and were excluded; the analysis is based on 301 patients (131 hypertensives and
      170 normotensives). RESULTS: The prevalence of additional risk factors, heart
      failure, prior myocardial infarction and prior revascularization was similar in
      the two groups of patients. An abnormal stress echocardiogram was detected in 101
      (59%) normotensives and 80 (61%) hypertensives (NS), while 113 (66%)
      normotensives and 83 (63%) hypertensives (NS) showed abnormal myocardial
      perfusion. The agreement was 81% (kappa = 0.59) in hypertensives and 82% (kappa =
      0.62) in normotensives. During 7.3 +/- 2.8 years of follow-up, 17 (13%)
      hypertensives and 26 (15%) normotensives died from cardiac causes (P = 0.62). In
      normotensives, the annual mortality rate was 0.8 for normal echo and 1.3 for
      normal scan, 2.8 for abnormal echo and 2.6 for abnormal scan. In hypertensives,
      it was 0.5 for normal echo, 0% for normal scan, 2.6 for abnormal echo and 2.8 for
      abnormal scan. Each test was associated with higher survival in the case of
      negative compared to positive results in both normotensive and hypertensive
      patients (log-rank chi-square 16.4, P < 0.001). CONCLUSIONS: Dobutamine stress
      echocardiography and SPECT are equally effective in predicting long-term cardiac
      death in both normotensive and hypertensive patients.

PMID- 15942466
TI  - The use of a telematic connection for the follow-up of hypertensive patients
      improves the cardiovascular prognosis.
AB  - BACKGROUND: Inadequate blood pressure (BP) control could be due to incorrect
      management of hypertensives caused by the lack of interaction between general
      practitioners (GP) and hypertension specialists. OBJECTIVES: To test the
      effectiveness on BP and total cardiovascular risk (TCVR) control of an internet
      based digital network connecting specialists and GPs. METHODS: We created a
      network among the Hypertension Clinic, Federico II University (Naples, Italy), 23
      hospital-based hypertension clinics and 60 GPs from the area (CampaniaSalute
      Network, CS). Randomized GPs enrolled in CS could update online records of
      patients (n = 1979). As a control, we included 2045 patients referred to the
      specialist clinics by GPs from outside the network. All patients completed a 2
      year follow-up. RESULTS: CS provided a larger reduction in BP [systolic/diastolic
      BP (SBP/DBP): 7.3 +/- 0.4/5.4 +/- 0.3 versus 4.1 +/- 0.4/3.1 +/- 0.26 mmHg, CS
      versus control; P < 0.001 for both] and percentage of patients with BP < 140/90
      mmHg (CS versus control: baseline, 33 versus 34%, NS; end of follow-up, 51 versus
      47%, chi = 13.371; P < 0.001). A European Society of Hypertension-European
      Society of Cardiology (ESH/ESC) TCVR score was calculated [from 1 (average) to 5
      (very high TCVR)]. The CS group showed a reduction in the mean TCVR score (CS:
      from 3.5 +/- 0.02 to 3.2 +/- 0, P < 0.01, ANOVA; control group: 3.5 +/- 0.03 to
      3.4 +/- 0.03, NS) and, accordingly, fatal and non-fatal major cardiovascular
      events (MACE) were less frequent (2.9 versus 4.3%; chi = 5.047, P < 0.02). CS
      predicts fewer MACE in multiple binary regression analysis (beta:-7.27, P <
      0.008) reducing the risk for MACE compared to control [odds ratio (OR): 0.838;
      95% confidence interval (CI): 0.73-0.96]. CONCLUSION: Our results support the
      idea that telemedicine can achieve better control of BP and TCVR.

PMID- 15942467
TI  - Cost effectiveness of losartan in patients with hypertension and LVH: an economic
      evaluation for Sweden of the LIFE trial.
AB  - OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol
      from a Swedish national health system perspective. DESIGN: The Losartan
      Intervention For Endpoint reduction in hypertension study (LIFE) was a double
      masked, randomized trial of losartan versus atenolol in 9193 patients with
      essential hypertension and left ventricular hypertrophy (LVH) ascertained by
      electrocardiography. Losartan reduced the primary composite end point of
      cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021)
      and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of
      blood pressure control. METHODS: Life years gained was estimated by combining the
      absolute risk reduction in stroke with the life years gained by preventing
      stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the
      absolute risk reduction in stroke with the QALYs gained by preventing stroke.
      QALYs were estimated by weighting life years by health-related quality of life
      (QoL), as measured with visual analogue scale (VAS) data collected in the trial.
      Net costs were defined as the total of study medication cost, stroke-related
      costs, and costs of increased survival. Costs are in 2003 Swedish prices. All
      costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a
      stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence,
      losartan treatment resulted in a per patient increase of 0.092 life years [95%
      confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as
      compared with atenolol treatment. Losartan reduced direct stroke-related cost per
      patient by 1141 euros due to a lower cumulative incidence of stroke for losartan
      at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7,
      2.5). The reduction in stroke-related cost offset 80% of the added cost of
      losartan drug therapy. After inclusion of study medication cost, net cost per
      patient was 289 euros higher for losartan than atenolol. The net cost per QALY
      gained for losartan was 4188 euros (37,813 SEK), which is well within common
      Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective
      interventions. CONCLUSION: Based on the results from the LIFE trial, treatment
      with losartan compared with atenolol, in hypertensive patients with LVH, is a
      cost-effective intervention.

PMID- 15942468
TI  - Metabolic disturbances as strong determinator of kidney injury in essential
      hypertension.

PMID- 15942469
TI  - Korotkoff's sounds in pregnancy.

PMID- 15942470
TI  - Ethnic differences in microvascular structure and function.

PMID- 15942472
TI  - Home blood pressure monitoring.

PMID- 15942474
TI  - Good clinical practice: a plea for nuclear medicine.

PMID- 15942475
TI  - Good clinical practice: historical background and key aspects.
AB  - Clinical research trials (both academic and industry sponsored) are increasingly
      playing a role in various medical disciplines, including younger fields of
      clinical trial interest, such as nuclear medicine research. Knowledge for and
      compliance with good clinical practice (GCP) is essential for anyone involved. In
      this review article, key aspects of GCP and the responsibilities of
      investigators, monitors and sponsors are described. In addition, a comprehensive
      overview of the historical background on the development of GCP from the US Pure
      Food and Drugs Act of 1906 over the Nuremberg Code, the Kefauver-Harris
      Amendments and the Declaration of Helsinki until now is given. Knowledge of the
      historical background may help understand the developments in GCP.

PMID- 15942476
TI  - The good laboratory practice and good clinical practice requirements for the
      production of radiopharmaceuticals in clinical research.
AB  - Radiopharmaceuticals account for more than 95% of the group of sterile
      pharmaceutical products and should therefore be handled and produced with care.
      Since the introduction of the European directive, all pharmaceuticals used in
      clinical studies must be prepared under good manufacturing practice (GMP)
      conditions. This review aims to give an overview of the basic principles and
      guidelines for the preparation of radiopharmaceuticals. Special attention is
      given to the production area environment and personnel, the two basic
      requirements for GMP productions. Especially for the production area, two
      philosophies have to be combined: the cascade system of over-pressure for the
      production of pharmaceuticals and the under pressure system for the manufacturing
      of radioisotopes. Personnel should be selected based on education and regularly
      given special training for the handling of radioactive material. Compared to
      pharmaceuticals, radiopharmaceuticals have their own labels, taking into account
      their specific nature. Besides the standard quality control, other items for
      quality control of radiopharmaceuticals are also discussed in this article.

PMID- 15942477
TI  - Accurate dosimetry: an essential step towards good clinical practice in nuclear
      medicine.
AB  - In nuclear medicine, an increasing number of radiolabelled agents are under
      investigation for future use in diagnostic imaging and for applications in
      radionuclide therapy. All these studies require large amounts of human data to
      allow for statistical comparisons with existing and well established diagnostic
      or therapeutic methodologies. In the framework of a good clinical practice
      environment, clinical trials should be carried out according to international
      guidelines and regulations as described in the Declaration of Helsinki. Studies
      involving ionizing radiation, as is the case in nuclear medicine, require special
      consideration to comply with the ALARA (as low as reasonably achievable)
      principle. Special publications of the International Commission of Radiological
      Protection and the World Health Organization deal with this topic in medical
      research. From the legislation point of view, the 97/43/EURATOM Directive
      represents the reference to clinical research using ionizing radiation within the
      European Union. In order to keep the radiation dose of (healthy) volunteers as
      low as possible, predictive dosimetry studies based on in-vivo animal biokinetics
      are essential. On the other hand, patients included in dose-escalation
      radionuclide therapy trials should be monitored individually with respect to
      dosimetry of the tumour and the critical organs. In this paper the importance and
      methodology of contemporary patient dosimetry in diagnostic and therapeutic
      nuclear medicine research are reviewed. It is concluded that reliable dosimetry
      is essential in performing scientific clinical studies according to the principle
      of good clinical practice.

PMID- 15942478
TI  - Diabetes mellitus: evaluation of patients with known or suspected coronary artery
      disease and the role played by myocardial perfusion imaging.
AB  - Type 2 diabetes markedly increases cardiovascular risk, and patients often
      present with advanced and asymptomatic disease. The fact that diabetes is
      associated with an increased risk of acute coronary events and poor long-term
      survival makes a strong case for detecting coronary artery disease early, perhaps
      before clinical manifestation in this patient population. This article examines
      the role of myocardial perfusion scintigraphy in the diagnostic and prognostic
      evaluation of diabetic patients with suspected coronary artery disease and in
      screening high-risk asymptomatic diabetic patients.

PMID- 15942479
TI  - Patient dosimetry in radionuclide therapy: the whys and the wherefores.
AB  - The importance and methodology of contemporary patient dosimetry in well
      established radionuclide therapies are reviewed. The different protocols used for
      radioiodine treatment of thyrotoxicosis are discussed. Special attention is paid
      to patient dosimetry in the largest safe dose approach for curative radioiodine
      therapy of thyroid remnants and metastases in the post-surgical treatment of
      differentiated thyroid cancer. Nowadays, meta-[131I]iodobenzylguanidine (131I
      MIBG) therapy for neuroblastoma relies on bone marrow dose levels. Issues related
      to whole-body and tumour dosimetry in this type of radionuclide therapy, where,
      traditionally, dosimetry has played an important role, are discussed. A
      relatively large number of patients are treated with radiolabelled Lipiodol for
      hepatocellular carcinoma. Administered activities are restricted to 2.22 GBq (60
      mCi) when using 131I-lipiodol because of the radioprotection measures to be
      taken. These radiation protection issues can be avoided by using 188Re labelled
      Lipiodol allowing further dose escalation. The follow-up of these patients also
      necessitates whole-body dosimetry. It is concluded that for treatment of
      malignant diseases reliable patient dosimetry is now a keystone of high quality
      radionuclide therapy. Where dosimetry of present medical applications focuses
      generally on the critical organs, in the near future accurate 3-dimensional
      tumour dosimetry also will become feasible by the introduction of the combined
      SPECT-CT and PET-CT imaging systems in the dosimetric methodology. This will
      allow treatment protocols based on tumour dose prescriptions as performed in
      external beam radiotherapy.

PMID- 15942480
TI  - Ischaemic related transitory left ventricular dysfunction in 201Tl gated SPECT.
AB  - AIM: To report our data concerning the changes in post-stress and at-rest left
      ventricular ejection fraction and ventricular volumes in patients with thallium
      gated SPECT. METHODS: Post-stress and at-rest thallium gated SPECT was performed
      in 629 consecutive patients; left ventricular ejection fraction (LVEF), left
      ventricular volumes and quantitative perfusion data were obtained. Transitory
      left ventricular dysfunction was diagnosed when post-stress LVEF did not increase
      at least 5% from LVEF at-rest. RESULTS: In all patients post-stress LVEF was
      64%+/-17 while at-rest LVEF was 66%+/-15 (P=0.6). Post-stress end diastolic
      volume (EDV) was 142 ml+/-7, at-rest EDV was 141 ml+/-92 (P=0.57), post-stress
      end systolic volume (ESV) was 54 ml+/-51 and at-rest ESV was 56 ml+/-59 (P=0.38).
      Data from the perfusion study were used to divide patients into three groups:
      normal patients (group I), patients with total or partially reversible defects
      (group II) and patients with fixed defects (group III). In group I and group III
      patients LVEF at-rest was lower than post-exercise (LVEF 75%+/-11 vs 81%+/-10
      (P<0.001) and 57%+/-16 vs 60%+/-18 (P=0.025)), respectively. Patients in group II
      had a higher at-rest LVEF than post-exercise (LVEF 66%+/-14 vs 64%+/-16
      (P=0.003)). While the left ventriuclar volumes in group I and III patients
      decreased with exercise, group II patients had increased post-stress ESV.
      CONCLUSIONS: Post-stress and at-rest LVEF are similar when all patients are
      considered but significant differences appear when patients are divided according
      to the results of the perfusion study. Normal and fixed defect patients have
      increased post-exercise LVEF. Patients with reversible defects have decreased
      LVEF, which is largely due to an increased ESV. Transitory left ventricular
      dysfunction is related to the presence of reversibility and may benefit from
      revascularization.

PMID- 15942481
TI  - Dobutamine myocardial scintigraphy for the prediction of cardiac events after
      heart transplantation.
AB  - BACKGROUND: The long-term outcome after heart transplantation (HTx) is
      essentially influenced by the occurrence and extent of cardiac allograft
      vasculopathy (CAV). Single photon emission computed tomography-myocardial
      perfusion imaging (SPECT-MPI) has been shown to be a useful and cost-effective
      non-invasive method in patients with known or suspected coronary artery disease,
      but its role in detecting CAV remains unclear. AIM: To evaluate the accuracy and
      predictive value of dobutamine MPI in patients after HTx during a 12-month follow
      up. METHODS: Seventy-seven patients (60 males, 17 females) underwent a total of
      216 dobutamine MPI examinations over a period of 5 years. Examinations were
      obtained an average of 89+/-42 months after orthotopic HTx according to a 1-day
      protocol using 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) with and without
      attenuation correction. For the present study, findings from 77 MPI examinations
      (one MPI examination per patient) were analysed visually and semiquantitatively
      using a 20-segment model. Summed stress scores (SSS) and summed rest scores (SRS)
      were calculated and receiver operating characteristic (ROC) analysis was
      performed to detect optimum threshold values. Patients were followed up for 12
      months and cardiac events were registered. RESULTS: Cardiac events were observed
      in 10 of the 77 patients. Good interobserver agreement was found for global
      visual and SRS-/SSS-based analysis (kappa=0.74 and 0.66, respectively). SSS was
      superior to SRS in the detection of cardiac events. ROC analysis showed an
      optimized SSS threshold value of three. For predicting a cardiac event during the
      12-month follow-up, global visual and semiquantitative analysis reached
      sensitivities of 90% and 90%, specificities of 72% and 88%, accuracies of 74% and
      87%, positive predictive values of 32% and 53% and negative predictive values of
      98% and 98%, respectively. The sensitivity, specificity, accuracy and positive
      and negative predictive values for MPI to detect clinically relevant coronary
      artery stenoses (> or =50%) at conventional coronary angiography were 83%, 87%,
      86%, 56% and 96%, respectively. CONCLUSIONS: Non-invasive dobutamine MPI reliably
      identifies patients at risk for subsequent cardiac events in cases of CAV, with a
      high negative predictive value of 98% and an accuracy of 87%.

PMID- 15942482
TI  - Radioactive iodine therapy for malignant and benign thyroid disease: a Canadian
      national survey of physician practice.
AB  - BACKGROUND: Radioactive iodine (as Na131I) has been used in the diagnosis and
      treatment of thyroid disease for more than 60 years, but the various treatment
      centres in Canada have different practice patterns. AIM: To determine whether
      there is a definable, nationwide pattern of practice which may be used to
      elucidate standards of practice and clarify some issues that arise when multiple
      care-givers are involved. METHODS: A survey questionnaire was mailed to all sites
      licensed by the Canadian Nuclear Safety Commission to administer Na131I for
      benign and malignant thyroid therapy. A second mailing was sent to non
      responders. The questionnaire addressed the involvement of personnel: i.e., who
      prescribes, determines doses, obtains informed consent, counsels on radiation
      safety, administers the therapy, and follows the patient post-therapy. The survey
      also specifically addressed whether a nuclear medicine physician reviewed
      laboratory work or met with patients pre-therapy. RESULTS: The overall response
      rate was 60% (74/123) with representation from all Canadian provinces. The
      majority of respondents were physicians (78%). The data include 3447 benign
      thyroid therapies and 1202 malignant thyroid therapies. There are no significant
      regional differences in the average maximum dose administered for either benign
      or malignant thyroid therapies. The majority of therapies are administered in
      community and academic hospital settings. Endocrinologists most commonly
      prescribe Na131I for malignant thyroid therapies and nuclear medicine physicians
      for benign thyroid therapies. For all therapies nuclear medicine physicians most
      commonly obtain informed consent, determine the dose and provide radiation safety
      counselling. Nuclear medicine technologists most commonly administer the therapy
      and endocrinologists most commonly provide post-therapy follow-up. In the
      majority of centres, nuclear medicine physicians review the laboratory results
      for each patient's blood sample and meet with patients before therapy.
      CONCLUSIONS: Multiple health care specialists take part in Na131I therapy for
      both benign and malignant thyroid disease. In most centres, nuclear medicine
      physicians have major roles in the delivery of the treatments, including
      reviewing clinical and biochemical information. The findings of this study should
      provide reassurance to many centres and guidance to others to allow closer
      harmonization of practice.

PMID- 15942483
TI  - Management of 131I therapy for thyroid cancer: cumulative dose from in-patients,
      discharge planning and personnel requirements.
AB  - AIM: To provide a comprehensive overview with regard to the
      hospitalization/discharge planning and nursing staff requirements for the
      management of patients treated with radioiodine for differentiated thyroid
      carcinoma. METHODS: A statistical analysis of the fast clearance phase of 131I
      was performed in 265 hospitalized patients treated after total thyroidectomy with
      fixed doses ranging from 2590 to 9250 MBq. RESULTS: Two hundred and twenty-five
      cases were post-surgical ablation treatments and 40 cases were follow-up
      treatments. The 131I clearance was studied during hospitalization of 2-4 days. No
      clearance differences were found between the two groups. The median value of the
      biological half-time (T1/2bio) was 0.65 days, with a variability range of 0.30
      2.03 days. A statistical model for the distribution of T(1/2bio) was reported.
      Some patients on maintenance haemodialysis were also studied, with T(1/2bio)
      values ranging from 1.6 to 2.6 days. The weekly cumulative dose to personnel from
      external exposure, corresponding to the 95th percentile, ranged from 0.1 mSv per
      GBq of administered activity (mSv x GBq(-1)) with a totally ambulant patient to
      5.4 mSv . GBq with a totally helpless patient. With patients on maintenance
      haemodialysis, these values could increase from 1.2 to 1.7 times. The cumulative
      dose to close relatives was also estimated. The hospitalization times associated
      with 75% and 95% probabilities of patient discharge were calculated by varying
      the residual activity limit from 100 to 800 MBq. Finally, using the median
      T(1/2bio), personnel requirements were evaluated. With totally ambulant and semi
      ambulant patients, about 0.5 and 1.0 personnel units per GBq of weekly
      administered activity were needed so as not to exceed an annual planning dose of
      6 mSv per year. The treatment of patients with higher degrees of dependency was
      impractical. CONCLUSIONS: On the basis of statistical analysis, a better
      organization of in-patient treatment may be obtained, as well as more accurate
      preliminary evaluations of the cumulative doses to nursing staff and attending
      personnel, for the management of patients treated with radioiodine for
      differentiated thyroid carcinoma.

PMID- 15942484
TI  - Interpretation of 99mTc sestamibi parathyroid SPECT scan is improved when read by
      the surgeon and nuclear medicine physician together.
AB  - OBJECTIVE: Parathyroid gland localization and lateralization are important before
      surgery, particularly for minimally invasive parathyroidectomy (MIP) and
      recurrent hyperparathyroidism. We hypothesized that readings of Tc sestamibi
      scans with single photon emission computed tomography (SPECT) by a surgeon and
      nuclear medicine physician together (NMP+S) compared to a nuclear medicine
      physician alone (NMP alone) might affect scan interpretation accuracy. METHODS:
      Between May 1999 and December 2002, 127 hyperparathyroid patients had
      preoperative localization with sestamibi SPECT. Scans were prospectively
      interpreted by an endocrine surgeon and nuclear medicine physician attending
      together (NMP+S) and a nuclear medicine physician attending alone (NMP alone).
      These readings were compared to intra-operative findings, which served as the
      'gold standard'. RESULTS: There were 120 patients with primary
      hyperparathyroidism (55 underwent MIP) and seven with secondary or tertiary
      hyperparathyroidism; seven patients had recurrent hyperparathyroidism. Of 127
      patients, 83 had single adenomas; 27, double adenomas; 15, hyperplasia; one,
      MENIIA; and one, parathyroid cancer. Sensitivity and positive predictive values
      were 58.6% and 67.4% for NMP alone compared to 81.9% and 70.0% for NMP+S. The
      overall accuracy of correct localization was 45.7% vs. 60.6% (P<0.01) and of
      correct lateralization was 69.3% vs. 80.3% (P<0.01) for NMP alone versus NMP+S
      respectively. The most common finding interpreted incorrectly by NMP alone and
      correctly by NMP+S was an ectopic superior parathyroid adenoma in the inferior
      position. Ninety-eight per cent of patients were cured of their
      hyperparathyroidism. CONCLUSIONS: Parathyroid sestamibi SPECT scan interpretation
      by an endocrine surgeon reading with a nuclear medicine attending resulted in
      improved accuracy of gland localization and lateralization compared to a nuclear
      medicine attending reading alone. This improvement may be due to increased
      awareness of clinical factors and head-and-neck anatomy.

PMID- 15942485
TI  - Scintigraphic findings in osteoarticular brucellosis.
AB  - AIMS: To describe the distribution of bone and joint involvement in 197 patients
      with brucellosis, and to detail a spectrum of findings on bone scintigraphy in 38
      patients with brucellar spondylitis. METHODS: One hundred and ninety-seven
      patients (141 females, 56 males; age range, 5-77 years) with osteoarticular
      brucellosis were studied. Patients were classified into acute (62%) and chronic
      (38%) stages of the disease, and into age groups of less than 16 (1%), 16-30
      (17%), 31-45 (29%), 46-60 (37%) and over 60 (16%) years. All patients were
      evaluated with Tc-methylene diphosphonate bone scanning. Quantification of
      sacroiliac joint uptake was performed to improve the sensitivity for the
      detection of sacroiliitis. Plain radiography and computed tomography (CT) or
      magnetic resonance imaging (MRI) were performed, when required, to evaluate the
      areas of the skeleton that showed abnormal uptake on the bone scan. MRI and
      single photon emission computed tomography (SPECT) were performed in all patients
      who had spinal lesions. RESULTS: The sites most commonly affected were the
      sacroiliac joints (53%) and spine (19%), followed by the shoulders (16%).
      Osteoarticular involvement was more common in females (72%) than in males (28%),
      and the acute stage (62%) was observed more than the chronic stage (38%). Bone
      and joint involvement occurred at any age, but the most common age group was 46
      60 years. Eight scintigraphic patterns were identified in spinal involvement.
      CONCLUSION: Brucellosis may affect the musculoskeletal system at any site. Bone
      scan is a useful method to detect osteoarticular involvement in cases of relapse
      and progression. Spine involvement has the widest range of scintigraphic
      findings. A knowledge of the location and distribution of osteoarticular
      involvement as revealed on the bone scan of patients with brucellosis may be
      valuable in patient treatment and management.

PMID- 15942486
TI  - Inflammatory bowel diseases: clinical update of practical guidelines.
AB  - Idiopathic inflammatory bowel disease (IBD) includes a collection of disorders of
      the gastrointestinal tract of unknown aetiology, characterized by intestinal
      inflammation and a chronic relapsing course associated with local and systemic
      complications. Traditionally, IBD comprises two prototype entities, ulcerative
      colitis (UC) and Crohn's disease (CD) and an intermediate variant of these
      diseases, indeterminate colitis which shows overlapping features of the two major
      forms. Over the last few years, considerable progress has been made in our
      knowledge of the pathogenesis of IBD, which is complex and derives from genetic,
      environmental and immunological interactions. The aetiology remains unclear, but
      it is well established that the lesions and symptoms are associated with over
      production of pro-inflammatory cytokines. In this paper we briefly review the
      pathophysiology and the new therapeutic approaches to IBD, since from these, new
      achievement depends the appropriate diagnostic exams to be performed and
      diagnostic flow charts.

PMID- 15942487
TI  - Nuclear medicine imaging of inflammatory/infective disorders of the abdomen.
AB  - Different nuclear medicine modalities are currently used to study inflammatory
      and infective disorders of the abdomen. They are usually complementary to
      radiology and endoscopy, but they play a pivotal role in particular clinical
      situations. Several radiopharmaceuticals (e.g., 111In or 99mTc labelled white
      blood cells, monoclonal antibodies, human polyclonal immunoglobulins, 75Ga
      citrate) are commercially available, but they can not be used indifferently to
      study abdominal inflammatory disorders. The lack of comparative studies showing
      the accuracy of each radiopharmaceutical for the study of inflammatory/infective
      abdominal diseases does not allow the best nuclear medicine technique(s) to be
      chosen in an evidence-based manner. To this end we performed a meta-analysis of
      peer reviewed articles published between 1984 and 2004 describing the use of
      nuclear medicine imaging for the study of inflammatory bowel disorders,
      appendicitis and vascular graft infections. A guideline for the optimal
      radiopharmaceutical(s) to be used in each clinical condition and for different
      aims is provided.

PMID- 15942489
TI  - Intralesional injection of Tisseel fibrin glue for resection of lymphangiomas and
      other thin-walled orbital cysts.
AB  - PURPOSE: Surgical removal of orbital lymphangiomas is often difficult because the
      capsule of these lesions is fragile, and, once violated, it tends to collapse,
      making identification of residual tumor difficult and dissection often
      incomplete. A surgical technique combining partial controlled decompression of
      the lesion with intralesional injection of Tisseel fibrin glue is evaluated to
      determine its effectiveness in resecting the lesion and preventing recurrences.
      METHODS: This is a retrospective interventional case series. Three young
      patients, two with lymphangiomas and one with congenital hydrocystoma, underwent
      surgical resection of their thin-walled cystic lesions of the orbit with the use
      of intralesional injection of Tisseel fibrin glue. Resolution of the signs and
      symptoms, complications of the surgery, and recurrence of bleeding are the
      parameters studied. RESULTS: All 3 patients had improvement of their signs and
      symptoms. None had complications related to the surgery, and no recurrence of
      bleeding occurred during the follow-up period. CONCLUSIONS: Our study suggests
      that this surgical technique with intralesional injection of Tisseel fibrin glue
      is an effective treatment modality for the resection of lymphangiomas and other
      orbital thin-walled cystic lesions.

PMID- 15942490
TI  - Lymphoproliferative disease of the ocular adnexa: a clinical and pathologic study
      with statistical analysis of 69 patients.
AB  - PURPOSE: To evaluate the clinical features, treatment, and outcomes of a cohort
      of patients with ocular adnexal lymphoproliferative disease classified according
      to the World Health Organization modification of the Revised European-American
      Classification of Lymphoid neoplasms and to perform a robust statistical analysis
      of these data. METHODS: Sixty-nine cases of ocular adnexal lymphoproliferative
      disease, seen in a tertiary referral center from 1992 to 2003, were included in
      the study. Lesions were classified by using the World Health Organization
      modification of the Revised European-American Classification of Lymphoid
      neoplasms classification. Outcome variables included disease-specific survival,
      relapse-free survival, local control, and distant control. RESULTS: Stage IV
      disease at presentation, aggressive lymphoma histology, the presence of prior or
      concurrent systemic lymphoma at presentation, and bilateral adnexal disease were
      significant predictors for reduced disease-specific survival, local control, and
      distant control. Multivariate analysis found that aggressive histology and
      bilateral adnexal disease had significantly reduced disease-specific survival.
      CONCLUSIONS: The typical presentation of adnexal lymphoproliferative disease is
      with a painless mass, swelling, or proptosis; however, pain and inflammation
      occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor
      histology, primary or secondary status, and whether the process was unilateral or
      bilateral were significant variables for disease outcome. In this study, distant
      spread of lymphoma was lower in patients who received greater than 20 Gy of
      orbital radiotherapy.

PMID- 15942491
TI  - Frosted jones pyrex tubes.
AB  - PURPOSE: To describe the use of a new, frosted Jones Pyrex tube in the treatment
      of obstructed canaliculi of the upper lacrimal system. The frosted Jones tube
      retains the advantages of the traditional smooth Pyrex tube yet appears to
      improve the positional stability in the surgically created fistula. METHODS: Ten
      patients of a single surgeon who had previously undergone external
      conjunctivodacryocystorhinostomy and placement of a Jones Pyrex tube, with
      subsequent Pyrex tube extrusion, were included in the study. All had previous
      success with Pyrex tubes, with follow-up ranging from 1 month to 14 years. In
      each case, when the patient presented with an extruded tube, it was replaced with
      a frosted Jones tube (Weiss Scientific Glass Blowing Company, Portland, OR,
      U.S.A.). RESULTS: In this preliminary study, none of the 10 patients fitted with
      a frosted Jones Pyrex tube had a recurrence of extrusion. All patients reported
      proper functioning of the tubes, with no complaints of epiphora or discomfort.
      CONCLUSIONS: Compared with a standard Jones Pyrex tube, a frosted tube functions
      equally well and reduces the possibility of extrusion, which is the main
      complication of traditional conjunctivodacryocystorhinostomy. We have exchanged
      smooth tubes for frosted tubes in patients who have had extrusion of the original
      tube, and we are currently investigating primary placement of the frosted Jones
      Pyrex tube.

PMID- 15942492
TI  - Incidence of infraorbital hypesthesia and sinusitis after orbital decompression
      for thyroid-related orbitopathy: a comparison of surgical techniques.
AB  - PURPOSE: To compare the incidence of postoperative infraorbital (V2) hypesthesia
      and sinusitis between transantral/Caldwell-Luc and transconjunctival orbital
      decompression for thyroid-related orbitopathy. METHODS: A retrospective review of
      all orbital decompressions from January 1994 to January 2001 performed by one
      surgeon was done. Seventy-eight patients (133 orbits) with thyroid-related
      orbitopathy underwent orbital decompression for compressive optic neuropathy,
      exposure keratopathy, or uncontrolled intraocular pressure. Main outcome measures
      were the presence of V2 hypesthesia and sinusitis determined at 3 postoperative
      evaluations (1 to 2 weeks, 1 to 3 months, 3 to 6 months). RESULTS: The incidence
      of V2 hypesthesia in the transconjunctival group declined from 29.2% (19/65) to
      6.1% (4/65), whereas the incidence of V2 hypesthesia in the transantral/Caldwell
      Luc group decreased from 68.2% (43/63) to 46% (29/63) over the postoperative
      course. The rate of sinusitis in the transconjunctival group stayed constant at
      6.1% (4/65) at early and late postoperative visits, whereas the transantral group
      rate of sinusitis declined from 33.3% (21/63) to 9.5% (6/63). CONCLUSIONS:
      Transconjunctival orbital decompression results in a statistically significant
      decrease of early and late postoperative infraorbital hypesthesia and early
      postoperative sinusitis when compared with the transantral approach.

PMID- 15942493
TI  - Acquired lower eyelid epiblepharon in patients with thyroid eye disease.
AB  - PURPOSE: To describe a series of patients with acquired epiblepharon secondary to
      thyroid-related orbitopathy. METHODS: Retrospective case series of 9 patients
      with thyroid-related orbitopathy who had epiblepharon. RESULTS: Seven patients
      had epiblepharon in both lower eyelids and 2 patients had it in one lower eyelid.
      Six of the 9 patients were Asian. Each patient had punctate keratopathy.
      Epiblepharon resolved in all but one patient after treating coexisting
      manifestations of thyroid-related orbitopathy. One patient required epiblepharon
      repair. CONCLUSIONS: We describe a new finding of acquired epiblepharon in the
      setting of thyroid-related orbitopathy. The majority of patients have spontaneous
      resolution of the epiblepharon after other surgical procedures for thyroid
      related orbitopathy.

PMID- 15942494
TI  - Octyl-2-cyanoacrylate tissue adhesive in external dacryocystorhinostomy.
AB  - PURPOSE: To review our experience using octyl-2-cyanoacrylate for closing the
      cutaneous incision in external dacryocystorhinostomy (DCR). METHODS: A
      retrospective review was performed of all cases of external DCR with
      cyanoacrylate wound closure performed during a 12-month period. At the completion
      of the DCR, octyl-2-cyanoacrylate was used to close the incision. No subcutaneous
      sutures were placed to approximate the wound edges. Fifteen seconds of drying
      time elapsed before a second application of the adhesive was applied. Follow-up
      consisted of examinations at 1 week, 1 month, and 3 months after surgery.
      RESULTS: Twenty-one cases of wound closure using octyl-2-cyanoacrylate in
      external DCR were performed on 19 patients. Cyanoacrylate was applied to the
      wound without complications, and all patients had excellent closure of the wound
      with the cyanoacrylate at the end of the case. No wound infections were noted
      during the follow-up period. One patient had a wound dehiscence that was treated
      with forceps debridement of residual cyanoacrylate and reapplication of
      additional octyl-2-cyanoacrylate. One patient had hypertrophic scar formation
      that resolved with daily massage. In all patients, the incision was believed to
      be aesthetically equivalent to the expected appearance of suture closed DCR
      incisions. CONCLUSIONS: Closure of the DCR incision with cyanoacrylate is safe,
      quick, does not compromise wound integrity, and provides an aesthetic result that
      is equivalent to suture wound closure. Additional benefits could potentially
      include safer operative environment and postoperative convenience for patient and
      surgeon.

PMID- 15942495
TI  - Local versus general anesthesia for external dacryocystorhinostomy in young
      patients.
AB  - PURPOSE: To compare the effectiveness, complications, and patient acceptance of
      local anesthesia with general anesthesia in young patients for external
      dacryocystorhinostomy (DCR). METHODS: Data were prospectively collected over an 8
      year period (1996-2004) on young patients (mean age: 22.64+/-1.71) undergoing
      external DCR in Gulhane Military Medical Academy. Patients were randomly
      allocated in two groups: general anesthesia (GA) and local anesthesia (LA). Of
      the 480 DCR procedures, 182 were performed with general anesthesia (44
      bilateral), 298 were performed with local anesthesia (32 bilateral). Visual
      analogue scales were recorded in the postoperative 2-hour period. Postoperative
      nausea and vomiting (PONV), epistaxis, length of hospital stay, and
      intraoperative bleeding were noted. RESULTS: Patients in both groups reported
      being comfortable during and immediately after surgery. Only 2 patients in the LA
      group required additional local anesthetic because of pain. Intraoperative
      bleeding was lower in the LA group. Analgesic requirement and signs of nausea and
      vomiting in the GA group were higher in the early postoperative period (p<0.05).
      The incidence of PONV was higher (p<0.05) in the GA group. Postoperative
      epistaxis was observed in 12 patients in the GA group and just 2 patients in the
      LA group. Length of hospital stay was 2.29+/-0.46 days in the GA group, and
      1.23+/-0.42 days in the LA group (p<0.01). CONCLUSIONS: Local anesthesia in DCR
      is safe and comfortable when proper anatomical approach to nerve blocks is
      performed correctly. Local anesthesia in young patients undergoing external DCR
      is a good alternative because it is cost-effective and it eliminates the
      complications of general anesthesia.

PMID- 15942496
TI  - Bacteriology of chronic dacryocystitis in a tertiary eye care center.
AB  - PURPOSE: To determine the current bacteriology of adult chronic dacryocystitis in
      a tertiary eye care center and compare it with previously reported studies.
      METHODS: Clinical and microbiological records of patients with diagnosis of
      chronic dacryocystitis between January 1999 and March 2002 were reviewed for age,
      sex, lacrimal sac side involved, and culture results. Patients younger than 16
      years of age and patients who were receiving any systemic or topical antibiotics
      were excluded from the study. RESULTS: One hundred eighty-eight adult patients
      with an average age of 50.5 years (range, 16 to 91 years), who had a diagnosis of
      chronic dacryocystitis, were identified. The study was predominated by female
      subjects (65.4%). Of the cultures from the nasolacrimal sac, 183 (97.3%) were
      positive for bacteria, with an average of 2.3 (1 to 6) microorganisms. More than
      2 microorganisms were present in 66.1% of the cultures, whereas a single
      microorganism was recovered from 33.9% of the cultures. The majority of
      microorganisms in our study were Gram-positive bacteria, representing 53.7% of
      the overall microorganisms cultured with a predominance of Staphylococcus
      species. Gram-negative bacteria were recovered from 26.0% of the specimens with
      predominance of Haemophilus influenzae. Anaerobic microorganisms were present in
      19.1% of the samples. The most frequently isolated anaerobic microorganisms were
      Propionibacterium acne and Peptostreptococcus species. CONCLUSIONS: Several
      bacterial species may be involved in the pathogenesis of chronic dacryocystitis
      in adults, and the majority of patients harbor multiple microorganisms in their
      nasolacrimal sacs. The high rate of microorganism-positive lacrimal sac cultures
      suggests that adult patients should be treated for their infection before any
      intraocular surgery because of the potential risk of infection.

PMID- 15942497
TI  - Inflammatory myofibroblastic tumor of the orbit presenting as a subconjunctival
      mass.
AB  - PURPOSE: To present a case of inflammatory myofibroblastic tumor in the anterior
      orbit and to describe its clinical features, diagnosis, and management. METHODS:
      Case report and literature review. RESULTS: A 10-year-old boy presented with
      diplopia and limited ocular motility in his right eye secondary to a
      subconjunctival mass in the right supranasal side. Incisional biopsy and
      debulking were performed. Histopathologic examination showed the proliferation of
      spindle-shaped myofibroblasts that were immunoreactive for smooth muscle actin
      and vimentin and infiltrate of inflammatory cells. CONCLUSIONS: We believe this
      is the first case of an inflammatory myofibroblastic tumor found localized in the
      orbit.

PMID- 15942498
TI  - Pericranium grafts for exposed orbital implants.
AB  - PURPOSE: To report the use of autologous pericranium grafts to cover exposed
      orbital implants. METHODS: A two-center consecutive case series of exposed
      orbital implants covered with autologous pericranium grafts. A patch of
      pericranium was harvested from the parieto-occipital region and was placed over
      the implant within a pocket between the implant and the Tenon capsule, followed
      by layered closure of Tenon and conjunctiva. RESULTS: Four patients (2 women, 2
      men) with a mean age of 37 years (range, 26 to 45 years) were included in the
      study. The mean follow-up period was 9.5 months (range, 7 to 12 months). In all
      cases, there was no recurrence of exposure and no donor site morbidity. A small
      pyogenic granuloma, arising from the conjunctival suture line, developed in one
      case. CONCLUSIONS: Autologous pericranium is a useful covering material for
      exposed orbital implants and may be used as an alternative to frontal periosteum.

PMID- 15942499
TI  - Enucleation with primary implant insertion for treatment of recalcitrant
      endophthalmitis and panophthalmitis.
AB  - PURPOSE: A prevalent conception exists that a two-stage operation (i.e., primary
      enucleation or evisceration with delayed secondary orbital implant insertion) is
      necessary when enucleation is required for recalcitrant endophthalmitis or
      panophthalmitis. The purpose of this study was to assess the utility of single
      stage enucleation and primary reconstruction in this setting. METHODS: In a
      retrospective interventional case series, 22 consecutive patients with advanced
      endophthalmitis or panophthalmitis refractory to prior medical treatment
      underwent enucleation and primary implant placement by a single surgeon between
      1991 and 2001. Eleven patients received hydroxyapatite implants; 11 patients
      received silicone implants. All patients were treated during surgery with
      intravenous antibiotics. All patients were evaluated for persistent local or
      systemic infection, implant exposure, extrusion, and successful fitting of their
      prostheses. RESULTS: No cases of persistent orbital cellulitis or meningitis
      occurred in any of the patients. Two patients with silicone orbital implants had
      extrusions; one was successfully managed with a secondary dermis-fat graft, and
      another patient who refused additional treatment was allowed to heal by secondary
      intention after the implant was removed. None of the patients with hydroxyapatite
      orbital implants had complications. All patients (20/20) who elected to undergo
      prosthetic fitting were successfully fit with prostheses. One patient elected not
      to pursue prosthetic fitting. One patient died of unrelated causes before a
      prosthesis could be fit. There were no objective findings to preclude successful
      fitting in either case. CONCLUSIONS: This study suggests that enucleation with
      primary orbital reconstruction and implant insertion for recalcitrant, fulminant
      ocular infection is an acceptable and advantageous treatment strategy. The risks
      and expenses associated with two separate surgeries are decreased,
      hospitalization time is potentially reduced, and subsequent rehabilitation can be
      initiated in a more timely fashion.

PMID- 15942500
TI  - Behavior of various orbital implants under axial compression.
AB  - PURPOSE: To determine and compare the amount of force required to disrupt the
      integrity of various orbital implants. METHODS: Compression tests were carried
      out by using a servo-electrical universal testing system on orbital implants
      including aluminum oxide (Bioceramic implant, FCI, Issy-Les-Moulineaux, France),
      coralline hydroxyapatite (HA) (Bio-Eye, Integrated Orbital Implants, Inc., San
      Diego, CA, U.S.A.), bovine HA (Molteno M-Sphere, IOP Inc., Costa Mesa, CA,
      U.S.A.), synthetic HA (FCI3, FCI, Issy-Les-Moulineaux, France), Chinese HA (H + Y
      Comprehensive technologies, Philadelphia, PA, U.S.A.), polylactic acid (Kinsey
      Nash Corporation, Duluth, MN, U.S.A.), porous polyethylene (Medpor, Porex
      Surgical Inc., College Park, GA, U.S.A.), and polymethylmethacrylate. RESULTS:
      Two basic groups of implants were identified: those that eventually reach a
      critical compression point and collapse (coralline HA, aluminum oxide, synthetic
      FCI3 HA, bovine HA, Chinese HA, and polymethylmethacrylate), and those that do
      not collapse but gradually compress with increasing load (porous polyethylene,
      polylactic acid). For similar-sized implants, the critical collapse point was
      earliest for the FCI3 HA implant, followed by the coralline HA, aluminum oxide,
      and polymethylmethacrylate implants. Smaller-sized collapsible implants showed
      earlier critical collapse points than larger-sized implants of similar material.
      CONCLUSIONS: A technique was established to assess the force required to disrupt
      the integrity of various orbital implants that is reliable, unbiased, and
      repeatable with any orbital implant. Orbital implants of different materials and
      sizes demonstrate different degrees of integrity. It is important to use similar
      sized implants when comparing the integrity of different implant materials
      because size influences the force required to overcome the structural integrity
      of the implant.

PMID- 15942501
TI  - Assessment of blepharospasm surgery using an improved disability scale: study of
      138 patients.
AB  - PURPOSE: To assess a new scale for grading functional disability in a series of
      patients operated on for blepharospasm resistant to treatment by botulinum toxin
      (BT) injections. METHODS: The bicentric study included 138 patients: 80 (58%)
      with essential blepharospasm; 46 (33%) with apraxia of eyelid opening; and 12
      (9%) with intermediate forms. They had undergone orbicularis myectomy (92 cases,
      67%), frontalis suspension (31 cases, 22%), or both (15 cases, 11%). Functional
      disability was assessed by using an original scale covering 6 daily life
      activities, each graded using 5 levels from 0 (no disability) to 4 (activity
      impossible). The score obtained was related to the total of activities actually
      performed to produce a functional disability score (FDS) from 0 to 100. Each
      patient's FDS was prospectively determined, before surgery and 3 months after
      surgery (M3). In patients who, after surgery, required a further course of BT
      injections, the FDS was assessed immediately before the third injection. RESULTS:
      The mean FDS fell significantly, from 78 +/- 15 (standard deviation) before
      surgery to 45 +/- 21 at M3 (p < 0.01%), whatever the clinical form of essential
      blepharospasm or surgical procedure. The mean postoperative FDS was significantly
      lower in the 62 patients (45%) weaned off BT than in the unweaned group,
      respectively (31 +/- 17 versus 56 +/- 18; p < 0.01). In the latter group, the
      mean FDS after BT reinjection (34 +/- 19) fell to a level comparable with that of
      the weaned patients. CONCLUSIONS: This accurate, easy-to-use scale makes it
      possible to quantify in patients with blepharospasm functional improvement as the
      result of surgery and, where applicable, of BT reinjection.

PMID- 15942502
TI  - Conjunctivodacryocystorhinostomy tube placement with a urologic catheter.
AB  - In an endoscopically performed conjunctivodacryocystorhinostomy, insertion of a
      Jones glass tube can be difficult if the nasal end of the tube draws soft tissue
      around the tunnel in front of the tube. A urologic Tiemann catheter has been used
      for Jones tube placement in 44 cases since 2001. The tube is put in the lumen end
      of the catheter, the tip of which is bulbous and gradually tapered in its
      diameter. The catheter can be easily inserted into the tunnel and pulled out of
      the nose with forceps, leaving the glass tube in the tunnel.

PMID- 15942503
TI  - Chronic Staphylococcus aureus infection leading to pyogenic granuloma and
      preventing socket re-epithelialization after orbital exenteration.
AB  - A 71-year-old woman underwent extenteration for conjunctival melanoma with
      orbital invasion. Her socket failed to epithelialize and contained a diffuse
      pyogenic granuloma that was caused by chronic Staphylococcus aureus infection.
      Extensive debridement and long-term intravenous antibiotics resulted in normal
      healing.

PMID- 15942504
TI  - Hughes technique, amniotic membrane allograft, and topical chemotherapy in
      conjunctival melanoma with eyelid involvement.
AB  - A 59-year-old woman presented with a pigmented mass in the inferior tarsal
      conjunctiva of the left eye with an associated diffuse, multifocal pigmentation
      involving largely the inferior half of the bulbar conjunctiva, fornix, and eyelid
      skin. Histopathologic examination of map biopsies disclosed conjunctival melanoma
      from primary acquired melanosis. Surgical excision of the inferior bulbar
      conjunctiva, fornix, and lower eyelid with histopathologic free margins was
      performed. Adjuvant cryotherapy was applied. The bulbar conjunctiva and lower
      fornix were reconstructed with an amniotic membrane allograft. Lower eyelid
      reconstruction was accomplished by use of the Hughes technique. Topical mitomycin
      C (0.04%) was applied after surgery. After 2 years of follow-up, no tumor
      recurrence has been detected and the eyelid and conjunctival defect have been
      satisfactorily corrected. This combined surgical procedure using amniotic
      membrane allograft and a composite tarsoconjunctival flap is shown to be useful
      in the treatment of an advanced conjunctival neoplasia with extensive eyelid
      involvement.

PMID- 15942505
TI  - Choroidal melanoma with massive extrascleral extension in a young black man.
AB  - The reported incidence of choroidal melanoma is low among the general population
      and is especially low among blacks. Choroidal melanoma is seen most commonly in
      whites in the sixth to seventh decades. The tumor is complicated by orbital
      invasion in only a small percentage of cases. This report describes the case of a
      38-year-old black man diagnosed with a choroidal melanoma of the right eye. The
      tumor exhibited extensive orbital invasion. Primary or metastatic disease
      elsewhere in the body was ruled out, and the patient underwent an eyelid-sparing
      orbital exenteration. Histopathologic examination of the orbital specimen
      confirmed the diagnosis of spindle cell-type choroidal melanoma. Orbital invasion
      by a primary choroidal melanoma in a black person under the age of 40 is highly
      unusual. To our knowledge, this represents the youngest reported case of
      choroidal melanoma with extrascleral extension in a black patient.
      Ophthalmologists should consider the possibility of this potentially deadly
      tumor, even in young, black patients.

PMID- 15942506
TI  - Bilateral upper eyelid edema in Melkersson-Rosenthal syndrome.
AB  - Melkersson-Rosenthal syndrome is an uncommon disorder characterized by a triad of
      facial nerve palsy, orofacial edema, and fissured tongue. A 42-year-old woman
      with Melkersson-Rosenthal syndrome presented with painless, nonpitting, bilateral
      asymmetric upper eyelid edema. The left eyelid was a bit larger than the right
      eyelid. CT and MRI demonstrated periorbital soft tissue thickening compatible
      with the microscopic findings of infiltration of lymphocytes, edema, and cystic
      dilatation of lymphatic vessels. After treatment by systemic doxycycline and
      corticosteroid, she showed some improvement of the eyelid edema. Isolated
      bilateral eyelids swelling may be observed in Melkersson-Rosenthal syndrome. In
      the case of unexplained nonpitting eyelid edema, biopsy should be performed.

PMID- 15942507
TI  - Compressive optic neuropathy due to orbital metastasis of a sacral chordoma: case
      report.
AB  - A 44-year-old man presented with unilateral proptosis and progressively
      deteriorating vision of his left eye over a 2-week period. He had a history of
      recurrent sacral chordoma for 1 year that had previously been treated with
      combined surgical excision, chemotherapy, and radiation therapy. MRI showed
      compression of the optic nerve by an orbital mass that proved to be an orbital
      metastasis of his sacral chordoma. The tumor mass was excised subtotally, and
      adjuvant orbital radiation therapy was administered.

PMID- 15942508
TI  - Primary orbital melanoma associated with a blue nevus.
AB  - A 43-year-old white woman presented with a sudden pain and protrusion of the
      right eye, along with decreased vision. Orbital CT revealed a well-demarcated
      lesion in the right intraconal space. After surgical excision, the
      histopathologic examination revealed a malignant melanoma with a predominant
      epithelioid cell type, probably arising in a blue nevus. The patient was treated
      with exenteration followed by radiotherapy.

PMID- 15942510
TI  - Re: "Localized inferior orbital fibrosis associated with porcine dermal collagen
      xenograft orbital floor implant".

PMID- 15942511
TI  - Budesonide offers no advantage when added to oral dexamethasone in the treatment
      of croup.
AB  - OBJECTIVE: To evaluate the effect of adding inhaled budesonide (2 mg) to oral
      dexamethasone 0.15 mg/kg in children hospitalized with croup. SETTING:
      Observation ward of a Tertiary Paediatric Hospital Emergency Department.
      SUBJECTS: Seventy-two children (age range 3 to 126 months) hospitalized with
      croup. INTERVENTION: Children randomized to receive either 2 mg of nebulized
      budesonide or placebo, with all children receiving a single oral dose of 0.15
      mg/kg dexamethasone. OUTCOME MEASURES: Primary outcome was duration of hospital
      stay. Other measures included croup scores from 0 to 12 hours, use of nebulized
      epinephrine, duration of croup symptoms, duration of viral symptoms, and return
      to medical care for croup or for any other reason following discharge from
      hospital. RESULTS: Baseline characteristics for the 2 groups were similar. There
      was no difference in time to discharge for the 2 groups or for other outcome
      measures with a risk ratio of 1.3 (95% confidence intervals of 0.82 and 2.1).
      CONCLUSIONS: The addition of inhaled budesonide (2 mg) to oral dexamethasone
      (0.15 mg/kg) offers no advantage in the treatment of children hospitalized with
      croup.

PMID- 15942512
TI  - Nonemergent emergency room utilization for an inner-city pediatric population.
AB  - OBJECTIVE: To identify patient reasons for accessing an urban Pediatric Emergency
      Room (PER) for primary care and to explore attitudes and practice regarding
      alternative sources for their medical home. METHODS: A total of 210
      questionnaires, consisting of 24 questions each, were completed in a face-to-face
      interview performed by trained interviewers. Questions asked included sources of
      medical care, frequency of use, and factors that went into caregiver decisions
      for using different sources of care. RESULTS: Caregivers choose the PER because
      of the short amount of time it takes for their child to be seen and discharged by
      a physician. Nearly 60% ranked wait time to see a doctor more important than
      seeing the same doctor every time (37.6%). About one-third of caregivers
      routinely brought their children to the PER for illness that is not serious. Only
      77% of caregivers claimed that their children have a regular doctor. Many
      caregivers cited that they are seen more by their regular doctor for shots (well
      visits) than for ill visits and are seen in the PER for illness. In this study,
      56% of children did not see the same regular doctor as their siblings.
      CONCLUSIONS: Efficiency and speed of health care delivery is of prime importance
      to this primarily Medicaid urban population. If strategies are to be implemented
      to attract these patients to a medical home that will strengthen their ties to
      their regular doctor, then the needs prioritized by the caregiver must be taken
      into consideration.

PMID- 15942513
TI  - Significant reduction in delayed diagnosis of injury with implementation of a
      pediatric trauma service.
AB  - BACKGROUND: The occurrence of delayed diagnosis of injury (DDI) among pediatric
      trauma patients represents a breakdown in trauma care. Although some DDI may be
      unavoidable, the rate of DDI may be used as a measure of quality improvement.
      OBJECTIVE: We sought to investigate DDI in admitted pediatric trauma patients
      while a designated pediatric trauma response team was used and compare this with
      the prior incidence of DDI (4.3%) before initiation of the response team.
      METHODS: Primary Children's Medical Center (PCMC) is a regional tertiary
      pediatric trauma center. This analysis used the prospectively gathered PCMC
      Trauma Database, and included all hospitalized pediatric trauma patients from
      1997 through 2000. RESULTS: A total of 3265 patients were included; no patients
      were excluded. A DDI occurred in 15 (0.46%; 95% CI: 0.31, 0.79) trauma patients.
      The DDI patients were more severely injured with significantly higher Injury
      Severity Scores, lower TRISS Probability of Survival values, longer
      hospitalizations (P < or = 0.05, Mann-Whitney U), and were more frequently
      admitted to the PICU (P < or = 0.05, chi2) than the non-DDI patient population.
      In a previous study, our incidence of missed injury was 4.3% (50/1175; 95% CI:
      3.3, 5.6); with implementation of a designated trauma response team and trauma
      service, the incidence of DDI was reduced nearly 10-fold to 0.46% (15/3265; 95%
      CI: 0.31, 0.79). CONCLUSIONS: Implementation of an effective trauma team and
      trauma service was associated with a significant reduction in DDI.

PMID- 15942515
TI  - Pyomyositis: a fatal case in a healthy teenager.
AB  - Pyomyositis is a common disease in the tropics that is reported with increasing
      frequency in the United States. We describe an unusually fulminant, fatal case in
      a previously healthy adolescent male. This case illustrates the clinical
      progression of pyomyositis from localized muscle infection to disseminated
      disease, and highlights the importance of considering this rare diagnosis in any
      stage of occult sepsis.

PMID- 15942514
TI  - The ill child in the emergency department and the accompanying people: a cross
      sectional analysis.
AB  - OBJECTIVE: The objective of this study is to investigate relationship between the
      number of the family members visiting the emergency department with pediatric
      patients and patient characteristics such as age, insurance status, traumatic
      complaint, whether event was acute or not, and to estimate number of family
      members who had any time off from their work among this group. METHOD: A
      prospective cross-sectional study was performed using a questionnaire which
      included demographic characteristics, number of family members, number of family
      members who were taking hours off from work. In the 15-day period (1-15 August
      2003), all persons who accompanied the children to the university-based PED
      (annual volume: 18,000) were asked to participate in the study. RESULTS: A total
      of 575 persons accompanied the 300 children seen in PED (1.92 persons per child).
      Number of persons accompanying the children was found to be inversely related to
      age (Pearson correlation, P = 0.000). Seventy-nine children (32.1%) of those with
      acute complaints had family members who took time off from their work, whereas 29
      (53.70%) of those with chronic illnesses had such family members (P = 0.003). The
      mean number of family members of children who had been referred from another
      healthcare institution was 2.06 +/- 0.77, whereas the mean number of family
      members of patients who presented directly to the PED was 1.85 +/- 0.63 (P =
      0.013). The mean number of family members of patients who had insurance for their
      child and those who do not have were 1.84 +/- 0.66 and 2.06 +/- 0.71,
      respectively, (P = 0.001). CONCLUSIONS: Numbers of family members were positively
      associated with a history of referral to another institution for the same reason,
      and inversely related to the parents' age and insurance status.

PMID- 15942516
TI  - Hypoglycemic seizure in Munchausen-by-proxy syndrome.

PMID- 15942517
TI  - Atypical presentation of shock from acute adrenal insufficiency in an adolescent
      male.
AB  - OBJECTIVE: To report an atypical presentation of shock and acute adrenal
      insufficiency in an adolescent male. CASE SUMMARY: A 14-year-old boy with a
      history of nocturnal enuresis presented with a clinical picture suggestive of
      septic shock refractory to aggressive fluid and vasopressor management. History
      and physical examination were suggestive of shock secondary to an infectious
      etiology, associated with skin findings of hyperpigmentation. The laboratory
      studies were remarkable for normal sodium, potassium, glucose, as well as normal
      renin levels. Hydrocortisone therapy led to improvement of his blood pressure and
      allowed weaning of vasopressor medications. Further laboratory studies, including
      adrenocorticotropic hormone stimulation test and adrenal antibodies, confirmed
      the diagnosis of primary adrenal insufficiency. CONCLUSION: Acute adrenal
      insufficiency is an uncommon cause of shock in the adolescent population. We
      report a clinical presentation suggestive of shock secondary to acute adrenal
      insufficiency remarkable for an atypical clinical and laboratory presentation. We
      further provide information on the management of acute adrenal crisis.

PMID- 15942518
TI  - Gradenigo syndrome: a rare but serious complication of otitis media.

PMID- 15942519
TI  - Subacute leg pain.

PMID- 15942520
TI  - The assessment and management of hypertensive emergencies and urgencies in
      children.
AB  - Although the prevalence of hypertension in the pediatric population is estimated
      at only 1% to 2%, hypertensive urgencies and emergencies may be encountered in
      the emergency department. Efficient management of these children is of utmost
      importance to avoid some of the life-threatening complications associated with
      hypertension and its treatment. This article serves to review some of the
      important aspects of pediatric hypertensive emergencies, including diagnosis,
      emergency department investigations, and pharmacologic management.

PMID- 15942522
TI  - Sick sisters.

PMID- 15942523
TI  - Acute ataxia in an infant.

PMID- 15942524
TI  - ECGs in the ED.

PMID- 15942525
TI  - Pediatric emergency medicine fellowships adopt a new application process.
AB  - The growth of the subspecialty of pediatric emergency medicine has created a
      subsequent growth in the demands of pediatric emergency medicine fellowship
      training. To facilitate the application process for both applicants and
      fellowship training programs, a uniform application and uniform deadlines have
      been adopted by the Pediatric Emergency Medicine Fellowship Director's
      Subcommittee. The Electronic Residency Application Service will provide online
      support necessary for the implementation of this new process. A description of
      the new process and a description of theoretical benefits from this change are
      described. Pediatric emergency medicine fellowship applicants should be
      encouraged to investigate resources describing the new application process.

PMID- 15942534
TI  - Carbohydrate trends in alcoholic beverages.

PMID- 15942535
TI  - What is the hunger-obesity paradox?

PMID- 15942536
TI  - The reality in leadership.

PMID- 15942537
TI  - Local wellness policies and the dietary guidelines: what does it mean to you?

PMID- 15942538
TI  - Another type of intervention: treating obesity with medication.

PMID- 15942540
TI  - Infant feeding practices and early flavor experiences in Mexican infants: an
      intra-cultural study.
AB  - OBJECTIVES: The study explored the maternal beliefs and practices related to
      pregnancy, breastfeeding, and infant feeding among women living in several
      regions in Mexico. We hypothesized that, despite the culinary diversity within
      Mexico, there would be similar patterns in the types of flavors and foods eaten
      by mothers and fed to infants. DESIGN: A structured interview was conducted
      through personal interviews with mothers during routine visits to their local
      family medical units. The units were located in four regions in Mexico that
      represent the diversity of culinary practices characteristic of the country.
      SUBJECTS: A random sample of 101 women whose infants ranged in age from 6 days to
      9 months. RESULTS: Although the vast majority of mothers knew of its benefits and
      nursed their infants, breastfeeding during the first week of life was not
      exclusive; approximately one third of the infants were also fed teas, water,
      and/or formula. The feeding of teas continued throughout infancy in three of the
      regions, but the flavor of the tea differed. There were also regional
      similarities in the foods chosen and avoided during pregnancy and lactation and
      the type of first foods offered to the infants. CONCLUSIONS: The similarities in
      the types of foods fed to infants and eaten more of by mothers during pregnancy
      suggest that these cultural and regional practices contribute to the development
      of strong preferences for regional cuisines. The foods eaten by the mother during
      pregnancy and lactation form the basis of the child's weaning patterns.

PMID- 15942539
TI  - Food choices of low-income women during pregnancy and postpartum.
AB  - OBJECTIVES: The purpose of this study was to examine dietary behavior during
      pregnancy and postpartum in a multiethnic sample of low-income women. SUBJECTS:
      Participants were 149 Medicaid-qualified women (30% white, 24% African American,
      and 46% Hispanic; median age, 22 years). DESIGN: Subjects were recruited into a
      longitudinal cohort design 0 to 1 days following delivery. Dietary choices during
      pregnancy and the first 6 months postpartum were assessed via validated food
      frequency questionnaires administered at 6 weeks and 6 months postpartum,
      respectively. STATISTICAL ANALYSES PERFORMED: Frequencies and means were used for
      descriptive purposes. Paired and independent sample t tests were used for
      continuous variables; chi 2 and McNemar tests were used for categorical
      variables. RESULTS: In all subjects, mean daily servings of grains (7.4 vs 6.2, P
      <.004), vegetables (2.5 vs 2.0, P <.002), and fruit (3.4 vs 1.7, P <.001)
      declined following childbirth, while the percentage of energy from fat (37.3% vs
      38.4%, P <.023) and added sugar (14.4% vs 16.4%, P <.019) increased. Women who
      breastfed their infants at 6 months postpartum reported lower intakes of total
      fat (34.2% vs 37.9%, P <.005) during pregnancy and higher fruit (2.2 vs 1.6, P
      <.05) and vegetable (2.6 vs 1.8, P <.02) intakes in postpartum than those who
      bottle-fed. Also, a greater proportion of lactating than nonlactating women
      (66.7% vs 36.9%, P <.05) met recommendations for fruit intake during pregnancy.
      CONCLUSIONS: The findings suggest that the transition from pregnancy to
      postpartum may be associated with a negative impact on dietary behavior that
      could compromise nutritional status in low-income women.

PMID- 15942541
TI  - Compliance with dietary guidelines and relationship to psychosocial factors in
      low-income women in late postpartum.
AB  - OBJECTIVES: The goals were to evaluate compliance with the Dietary Guidelines
      among low-income women during late postpartum and to examine the relationship
      between psychosocial variables and dietary compliance. SUBJECTS/SETTING:
      Participants were 146 triethnic, low-income women who were recruited 0 to 1 days
      after childbirth and who visited a clinic site at 1 year postpartum. DESIGN: At 1
      year postpartum, multiple psychosocial characteristics were measured, and food
      choices and nutrient intakes were assessed via a validated food frequency
      questionnaire. Dietary guidelines index scores and measures of adherence to
      dietary recommendations were computed. STATISTICAL ANALYSES PERFORMED:
      Descriptive statistics, analysis of variance with post-hoc Scheffe tests, chi 2
      with follow-up tests of independent proportions, and Pearson correlation
      coefficients were utilized. RESULTS: For dietary compliance, 60% had adequate
      intakes of meat, but less than 30% met recommendations for grains, vegetables,
      fruits, dairy foods, total fat, and added sugar. Healthful weights (body mass
      index <25) were observed in 37% of women. Those in the highest tertile of dietary
      compliance had a more positive body image than those in the lowest tertile, and
      less neglect of self-care, weight-related distress, stress, depressive symptoms,
      and perceived barriers to weight loss ( P <.05). Dietary compliance and
      psychosocial scale scores did not vary by ethnicity. CONCLUSIONS: Adherence to
      dietary guidelines was limited in the low-income, postpartum women. Psychosocial
      variables, such as neglect of self-care, weight-related distress, negative body
      image, stress, and depressive symptoms were associated with less healthful diets
      and lifestyle in late postpartum. Programs that target diet-related behavior
      change in low-income women might be improved by inclusion of psychosocial
      assessment and counseling components.

PMID- 15942542
TI  - Produce programs help low-income women meet dietary guidelines.

PMID- 15942543
TI  - Size acceptance and intuitive eating improve health for obese, female chronic
      dieters.
AB  - OBJECTIVE: Examine a model that encourages health at every size as opposed to
      weight loss. The health at every size concept supports homeostatic regulation and
      eating intuitively (ie, in response to internal cues of hunger, satiety, and
      appetite). DESIGN: Six-month, randomized clinical trial; 2-year follow-up.
      SUBJECTS: White, obese, female chronic dieters, aged 30 to 45 years (N=78).
      SETTING: Free-living, general community. INTERVENTIONS: Six months of weekly
      group intervention (health at every size program or diet program), followed by 6
      months of monthly aftercare group support. MAIN OUTCOME MEASURES: Anthropometry
      (weight, body mass index), metabolic fitness (blood pressure, blood lipids),
      energy expenditure, eating behavior (restraint, eating disorder pathology), and
      psychology (self-esteem, depression, body image). Attrition, attendance, and
      participant evaluations of treatment helpfulness were also monitored. STATISTICAL
      ANALYSIS PERFORMED: Analysis of variance. RESULTS: Cognitive restraint decreased
      in the health at every size group and increased in the diet group, indicating
      that both groups implemented their programs. Attrition (6 months) was high in the
      diet group (41%), compared with 8% in the health at every size group. Fifty
      percent of both groups returned for 2-year evaluation. Health at every size group
      members maintained weight, improved in all outcome variables, and sustained
      improvements. Diet group participants lost weight and showed initial improvement
      in many variables at 1 year; weight was regained and little improvement was
      sustained. CONCLUSIONS: The health at every size approach enabled participants to
      maintain long-term behavior change; the diet approach did not. Encouraging size
      acceptance, reduction in dieting behavior, and heightened awareness and response
      to body signals resulted in improved health risk indicators for obese women.

PMID- 15942545
TI  - Breakfast consumption by African-American and white adolescent girls correlates
      positively with calcium and fiber intake and negatively with body mass index.
AB  - OBJECTIVE: To describe age- and race-related differences in breakfast consumption
      and to examine the association of breakfast intake with dietary calcium and fiber
      and body mass index (BMI). DESIGN: Data from the National Heart, Lung, and Blood
      Institute Growth and Health Study, a 9-year, longitudinal biracial cohort study
      with annual 3-day food records. SUBJECTS/SETTING: The National Heart, Lung, and
      Blood Institute Growth and Health Study recruited 2,379 girls (1,166 white and
      1,213 African American), aged 9 or 10 years at baseline for an observational
      study. Retention rates were very high at visits two through four (96%, 94%, and
      91%), but declined to a low of 82% at visit seven, and increased to 89% at visit
      10. MAIN OUTCOME MEASURES: Frequency of breakfast consumption, dietary calcium
      and fiber, and BMI. STATISTICAL ANALYSES: Generalized estimation equations
      methodology was used to examine differences in the frequency of breakfast eating
      by age and race. Generalized estimation equations analyses were also conducted to
      test whether breakfast consumption was predictive of intake of dietary calcium
      and fiber, and BMI, adjusting for potentially confounding effects of site, age,
      race, parental education, physical activity, and total energy intake. RESULTS:
      Frequency of breakfast eating declined with age, white girls reported more
      frequent breakfast consumption than African-American girls, and the racial
      difference decreased with increasing age. Days eating breakfast were associated
      with higher calcium and fiber intake in all models, regardless of adjustment
      variables. Days eating breakfast were predictive of lower BMI in models that
      adjusted for basic demographics (ie, site, age, and race), but the independent
      effect of breakfast was no longer significant after parental education, energy
      intake, and physical activity were added to the model. CONCLUSIONS: Dietetics
      professionals need to promote the importance of consuming breakfast to all
      children and adolescents, especially African-American girls.

PMID- 15942546
TI  - Promoting meal consumption among teens.

PMID- 15942547
TI  - Medications as adjunct therapy for weight loss: approved and off-label agents in
      use.
AB  - Although a nutritionally balanced, energy-controlled diet and regular exercise
      form the cornerstone of weight management, supporting therapies may include
      antiobesity medications when a clinician determines that pharmacologic assistance
      could contribute to treatment success. The US Food and Drug Administration has
      approved certain medications for helping achieve weight loss in patients with
      obesity or overweight who have comorbidities. However, some clinicians prescribe
      medications not approved for weight loss for this purpose. Evidence from clinical
      trials indicates that weight loss resulting from the use of many of these off
      label pharmaceutical agents is modest, but in a range that correlates with
      favorable modification of cardiovascular risk factors, and significant when
      compared with placebo plus diet and lifestyle modification. Clinical trials also
      demonstrate a slight but significant effect in the weight-maintenance phases
      following weight loss. Pharmacotherapy alone, without behavior modification, is
      not effective; patients who respond to medication typically regain weight when
      the drug is discontinued. The fact that many weight-loss medications are sold
      over the Internet without a prescription suggests that they are being used
      without medical supervision. The purpose of this review is to present evidence
      for and against the obesity medications currently used in clinical practice, and
      the possible role for these agents in a person's overall weight loss plan.

PMID- 15942549
TI  - Psychosocial influences in dietary patterns during pregnancy.
AB  - There is increasing evidence that psychosocial factors may affect dietary intakes
      and health. The current analysis examined the association of six indices of
      psychosocial well-being with dietary intake during pregnancy. One hundred thirty
      four women with low-risk, normal pregnancies participated in a cross-sectional,
      observational study that assessed dietary intake at 28 weeks' gestation.
      Psychosocial characteristics, including anxiety, depressed mood, anger, fatigue,
      social support, and stress were assessed between 24 and 32 weeks' gestation.
      Pearson product-moment correlations were calculated to determine the
      relationships between psychosocial factors and diet. Findings suggest that
      pregnant women who were more fatigued, stressed, and anxious consumed more foods,
      as evidenced by their increased macronutrient intakes, while appearing to have
      decreased intakes of some micronutrients. Psychosocial factors should be
      considered when counseling women regarding diet during pregnancy.

PMID- 15942550
TI  - Cholesterol-lowering benefits of oat-containing cereal in Hispanic americans.
AB  - This randomized, controlled trial of cholesterol lowering by an oat bran cereal
      containing beta glucan vs a corn cereal without soluble fiber in Hispanic
      Americans was conducted for 11 weeks. One-hundred fifty-two men and women, ages
      30 to 70 years, with baseline low-density lipoprotein cholesterol (LDL-C) levels
      between 120 and 190 mg/dL and triglycerides <400 mg/dL were included. After
      eating a National Cholesterol Education Program Step 1 diet for 5 weeks, subjects
      were randomly assigned to the corn or the oat cereal for the next 6 weeks. The
      daily dose of beta glucan was 3 g. Consumption of oat cereal was associated with
      a reduction in plasma levels of both total cholesterol (-10.9+/-21.6 mg/dL; 
      4.5%) and LDL-C (-9.4+/-20.3 mg/dL; -5.3%). Consumption of corn cereal did not
      affect either total cholesterol (+1.2+/-18.3 mg/dL; 1.1%) or LDL-C (+1.2+/-17.5
      mg/dL; 2.2%). Differences between the effects of the two cereals on total
      cholesterol and LDL-C were significant, P =.0003 and P =.0007, respectively.

PMID- 15942551
TI  - Adolescent girls in Maine are at risk for vitamin D insufficiency.
AB  - The objective was to determine the seasonal fluctuations in serum 25
      hydroxyvitamin D (25-OHD) in a group of healthy adolescents living in a northern
      climate. Twenty-three 9- to 11-year-old girls participated in the study from
      September 2000 to March 2003. Serum 25-OHD and parathyroid hormone levels were
      measured each September and March. Dietary intake of vitamin D was assessed each
      summer and winter. Summer-sun exposure was evaluated using reports of time spent
      outdoors. The mean decrease in serum 25-OHD from September to March was 28%.
      Vitamin D insufficiency (at least one serum 25-OHD level <50 nmol/L) was observed
      in 11 of 23 (48%) subjects. Four of 23 subjects (17%) exhibited vitamin D
      insufficiency in both September and March. Mean parathyroid hormone levels
      increased 4 pg/mL (15%) from September to March. Vitamin D intakes need to be
      increased in winter at northern latitudes.

PMID- 15942552
TI  - Prevalence of iron deficiency with and without anemia in recreationally active
      men and women.
AB  - The objective of this study was to determine the prevalence of iron deficiency
      with and without anemia in a convenience sample of trained male and female
      adults. One hundred twenty-one adults (72 female, 49 male) involved in aerobic
      training (11.2+/-6.3 hr/wk for >/=6 consecutive months), ages 18 to 41 years old,
      participated in an iron status screening. The concentrations of hemoglobin (Hb),
      ferritin, and transferrin receptor were measured in serum to determine the
      prevalence of iron deficiency with and without anemia. Eight individuals (seven
      female, one male) had iron deficiency with anemia (serum ferritin <16 microg/L;
      Hb<120 g/L female, <136 g/L male). Iron deficiency without anemia (serum ferritin
      </=16 microg/L) was found in 29% of female and 4% of male subjects. Determination
      of iron deficiency without anemia using the transferrin receptor-ferritin index
      (serum transferrin receptor:log serum ferritin>/=4.5) found 36% of female and 6%
      of male subjects to be iron deficient without anemia. Recreational athletes
      should be screened for iron deficiency without anemia using serum ferritin, serum
      transferrin receptor, and Hb.

PMID- 15942553
TI  - Position of the American Dietetic Association: benchmarks for nutrition programs
      in child care settings.
AB  - It is the position of the American Dietetic Association that all child care
      programs should achieve recommended benchmarks for meeting children's nutrition
      and nutrition education needs in a safe, sanitary, and supportive environment
      that promotes healthy growth and development. Use of child care is the norm for
      America's families. It is essential, therefore, that nutrition professionals work
      in partnership with child care providers and with children's families to ensure
      that meals and snacks consumed in child care settings meet children's nutrition
      needs and provide them with excellent models of healthy dietary patterns. This
      position provides guidance and information about resources for nutrition
      professionals, health care practitioners, child care providers, and parents
      regarding meal plans, food preparation and food service, physical and social
      environment, and nutrition consultation and training for child care.

PMID- 15942554
TI  - Medical nutrition therapy: the core of ADA's advocacy efforts (part 2).

PMID- 15942556
TI  - Medication effects on metabolic rate: a systematic review (part 2).

PMID- 15942560
TI  - Use of administrative data for clinical quality measurement.

PMID- 15942561
TI  - Objective radiologic analysis of ground-glass opacity aimed at curative limited
      resection for small peripheral non-small cell lung cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of the objective
      radiologic analysis of high-resolution computed tomographic images of small
      peripheral non-small cell lung cancer and to select the candidates for curative
      limited resection. METHODS: High-resolution computed tomographic images of 146
      surgically resected T1 N0 M0 peripheral non-small cell lung cancers were analyzed
      by using National Institutes of Health image software and classified on the basis
      of the percentage of ground-glass opacity within the tumor. RESULTS: Eighty-seven
      percent of tumors with ground-glass opacity ratios of 90% to 100% (type I) were
      diagnosed as noninvasive bronchioloalveolar carcinoma, whereas 55.6% of tumors
      with ground-glass opacity ratios of 50% to 89% (type II) consisted of
      adenocarcinoma. Tumors with ground-glass opacity ratios of 50% or more (type
      I/II) had no nodal involvement, whereas nodal metastases were identified in 20.0%
      of tumors with ground-glass opacity ratios of 10% to 49% (type III) and 24.4% of
      tumors with ground-glass opacity ratios of less than 10% (type IV). No tumors
      with ground-glass opacity ratios of 50% or more showed vessel infiltration,
      except for one lesion with a ground-glass opacity ratio of 50%. The 3-year
      disease-free survival was 97.7% for type I/II, 86.1% for type III, and 78.5% for
      type IV tumors. CONCLUSIONS: The objective quantitative radiologic analysis with
      National Institutes of Health image software exhibited a good correlation with
      the histologic classification, pathologic invasiveness, and postoperative outcome
      of small peripheral lung cancer. Patients with tumors that have ground-glass
      opacity ratios of greater than 50% are considered to be possible candidates for
      limited pulmonary resection.

PMID- 15942562
TI  - The accuracy of endoscopic ultrasonography with fine-needle aspiration,
      integrated positron emission tomography with computed tomography, and computed
      tomography in restaging patients with esophageal cancer after neoadjuvant
      chemoradiotherapy.
AB  - BACKGROUND: Patients with esophageal cancer who receive neoadjuvant
      chemoradiotherapy are restaged with computed tomography (CT), endoscopic
      ultrasound with fine needle aspiration (EUS-FNA), and integrated positron
      emission computed tomography (FDG-PET/CT), and the results affect treatment.
      METHODS: This is a prospective trial on a consecutive series of patients who had
      initial chest, abdomen, and pelvis CT scan; EUS-FNA; and fluoro-2-deoxy- d 
      glucose (FDG)-integrated PET/CT; neoadjuvant chemoradiotherapy; repeat staging
      tests; pathologic staging; and, if appropriate, resection with lymphadenectomy.
      The primary objective was to assess the accuracy of these 3 tests in restaging
      patients after neoadjuvant therapy. RESULTS: There were 48 patients (41 men), and
      41 underwent Ivor Lewis esophagogastrectomy with lymphadenectomy. The accuracy of
      each test for distinguishing pathologic T4 from T1 to T3 disease is 76%, 80%, and
      80% for CT scan, EUS-FNA and FDG-PET/CT, respectively. The accuracy for nodal
      disease was 78%, 78%, and 93% for CT scan, EUS-FNA and FDG-PET/CT, respectively (
      P = .04). FDG-PET/CT correctly identified M1b disease in 4 patients, falsely
      suggested it in 4 patients, and missed it in 2 patients, whereas for CT, it was
      3, 3, and 3 patients. Fifteen (31%) patients were complete responders, and FDG
      PET/CT accurately predicted complete response in 89% compared with 67% for EUS
      FNA ( P = .045) and 71% for CT ( P = .05). CONCLUSIONS: FDG-PET/CT is more
      accurate than EUS-FNA and CT scan for predicting nodal status and complete
      responders after neoadjuvant therapy in patients with esophageal cancer. FDG
      PET/CT and CT alone provide targets for biopsy, but results are often falsely
      positive.

PMID- 15942563
TI  - Evaluation of cyclooxygenase-2 inhibition in an orthotopic murine model of lung
      cancer for dose-dependent effect.
AB  - OBJECTIVES: Cyclooxygenase-2 plays a role in growth, apoptosis, angiogenesis, and
      metastasis in lung cancer. Inhibition of cyclooxygenase-2 with celecoxib has been
      shown to inhibit tumor growth. We evaluated the effect of increasing doses of
      celecoxib in a murine model of human lung cancer. METHODS: Human lung
      adenocarcinoma cells (A549) were implanted in the left lung upper lobe of mice
      with severe combined immunodeficiency syndrome. Mice were randomly assigned to 4
      groups at implantation (n = 10 per group): control, 125 mg/kg chow, 500 mg/kg
      chow, 1000 mg/kg chow. After 3 weeks, mice were killed, and a blinded observer
      measured total tumor volume. The dose effect of celecoxib was examined in vitro
      by studying cell proliferation, expression of cyclooxygenase-2 (mRNA and
      protein), and production of prostaglandin E 2 in unstimulated and interleukin
      1beta-stimulated cells. RESULTS: All 40 mice survived for 3 weeks with no
      observed toxicities. Total tumor volume was inhibited in each celecoxib group ( P
      = .0038, Welch analysis of variance): 206.7 +/- 119.5 mm 3 (control group), 41.4
      +/- 54.0 mm 3 (low-dose group), 34.5 +/- 39.3 mm 3 (medium-dose group), and 27.3
      +/- 53.6 mm 3 (high-dose group). In vitro celecoxib was effective at inhibiting
      production of prostaglandin E 2 , even in stimulated cells, although little
      effect was seen on cyclooxygenase-2 protein levels. Inhibition of proliferation
      was evident only at doses that exceeded those used in the animal model.
      CONCLUSION: Inhibition of cyclooxygenase-2 with low-dose celecoxib restricted the
      growth of lung cancer in this model. This might be mediated by prostaglandin E 2
      . Higher doses of celecoxib afforded no additional benefit. Chronic therapy with
      low-dose cyclooxygenase-2 inhibition has the potential to influence tumor
      progression in non-small cell lung cancer.

PMID- 15942564
TI  - High-dose radiotherapy in trimodality treatment of Pancoast tumors results in
      high pathologic complete response rates and excellent long-term survival.
AB  - OBJECTIVE: We sought to study the clinical characteristics and outcomes of
      patients treated with a surgery-inclusive multimodality approach for Pancoast
      tumors. METHODS: Clinical records of patients with Pancoast lung cancer who were
      enrolled for multimodality treatment between 1993 and 2003 at our institution
      were reviewed retrospectively. RESULTS: Thirty-six patients completed neodjuvant
      chemoradiation followed by en bloc surgical resection, whereas one patient
      received high-dose radiation alone followed by surgical intervention. There were
      22 men and 15 women. Thirty-four lobectomies and 3 pneumonectomies were
      performed. Pretreatment non-small cell lung cancer stages were IIB, IIIA, IIIB,
      and IV (presenting with solitary brain metastasis) in 18, 8, 6, and 5 cases,
      respectively. R0 resection was achieved in 36 (97.3%) patients. Operative
      mortality was 2.7% (n = 1). High-dose radiotherapy was successfully tolerated in
      all but 1 patient. Mean total radiation dose was 56.9 Gy. Pathologic complete
      response was found in 40.5% (n = 15) of patients. Recurrences were found in 50%
      (n = 18) of patients. Brain metastasis was the most common recurrence (n = 9),
      followed by other distant recurrences (n = 4) and local recurrences (n = 5).
      Median survival time for the group is 2.6 years, and median survival time
      (pathologic complete response) is 7.8 years. It is noteworthy that median
      survival time of patients with positive pretreatment lymph nodes (12 patients)
      was not reached. CONCLUSIONS: Surgical resection of Pancoast tumors after
      neoadjuvant high-dose radiation and chemotherapy can be safely performed. High
      dose radiation in trimodality treatment is well tolerated and might be
      beneficial. Similar to other studies, late central nervous system relapse is
      problematic and indicates a need for assessing the role of prophylactic cranial
      irradiation in this disease.

PMID- 15942565
TI  - Completion pneumonectomy for chronic mycobacterial disease.
AB  - OBJECTIVE: Patients with persistent pulmonary infections from mycobacterial
      disease present a difficult clinical challenge. These individuals typically have
      poor pulmonary function, malnutrition, and other comorbidities, and few
      guidelines exist regarding optimal therapy. We report our experience with
      completion pneumonectomy as part of a multidisciplinary treatment program for
      patients with recurrent, persistent mycobacterial disease. METHODS: During a 9
      year period, 26 consecutive patients underwent completion pneumonectomy for
      mycobacterial disease. All patients underwent intensive, guided preoperative
      antibiotic therapy and aggressive nutritional supplementation. Complete surgical
      resection of the remaining destroyed or infected lung tissue was performed, often
      through an extrapleural dissection with intrapericardial ligation of vessels.
      Vascularized tissue flaps were used whenever possible to buttress the bronchial
      stump closure. Postoperative management consisted of a multidisciplinary
      approach, with ongoing antibiotic and nutritional therapy. RESULTS: The primary
      organisms were Mycobacterium avium complex (n = 15), Mycobacterium tuberculosis
      (n = 5), Mycobacterium abscessus (n = 3), Mycobacterium xenopi (n = 2), and
      Mycobacterium chelonae (n = 1). Operative mortality was 23% (6/26): respiratory
      failure or adult respiratory distress syndrome in 2 cases, sepsis in 2,
      bronchopleural fistula in 1, and pulmonary embolism in 1. Significant morbidity
      occurred in 46% (12/26). Among the 17 long-term survivors, sputum conversion or
      discontinuation of medications was achieved in 14 (82%). Mean length of follow-up
      was 45 months (range 4-105 months). CONCLUSION: Completion pneumonectomy remains
      an important component of therapy in patients with mycobacterial disease who have
      had failure of previous therapy. Although associated with significant risks,
      successful outcomes can be achieved with an organized, multidisciplinary approach
      and careful postoperative follow-up.

PMID- 15942566
TI  - Annular or subvalvular approach to chronic ischemic mitral regurgitation?
AB  - OBJECTIVE: We sought to investigate whether annular or subvalvular interventions
      corrected chronic ischemic mitral regurgitation differently. METHODS: Sheep
      underwent placement of markers on the left ventricle, mitral annulus, papillary
      muscles (anterior and posterior), and both leaflet edges. A transannular suture
      (septal-lateral annular cinching) was anchored to the midseptal mitral annulus
      and externalized through the midlateral mitral annulus. Another suture (papillary
      muscle repositioning) from the posterior papillary muscle was passed through the
      mitral annulus near the posterior commissure and externalized. After 7 days, 3
      dimensional marker data were obtained before inducing posterolateral myocardial
      infarction. After 7 weeks, animals in whom chronic ischemic mitral regurgitation
      developed (n = 10) were restudied before and after pulling septal-lateral annular
      cinching or papillary muscle repositioning sutures. End-systolic septal-lateral
      annular diameter and 3-dimensional displacement of the papillary muscles and
      leaflet edges were computed. RESULTS: Infarction increased mitral regurgitation
      (0.6 +/- 0.5 to 2.3 +/- 1.1); mitral annular septal-lateral dilation (4 +/- 1
      mm); posterior papillary muscle displacement laterally (4 +/- 2 mm), posteriorly
      (9 +/- 3 mm), and toward the annulus (2 +/- 1 mm); posterior mitral leaflet
      apical tethering (3 +/- 1 mm); and interleaflet separation (+3 +/- 1 mm, P < .05
      baseline vs chronic ischemic mitral regurgitation). Septal-lateral annular
      cinching reduced septal-lateral dimension (-9 +/- 3 mm), corrected lateral
      posterior papillary muscle displacement (4 +/- 1 mm) and septal-lateral
      interleaflet separation (-4 +/- 2 mm), and decreased mitral regurgitation (0.6 +/
      0.6, P < .05 septal-lateral annular cinching vs chronic ischemic mitral
      regurgitation) without affecting posterior leaflet restriction. Papillary muscle
      repositioning reduced septal-lateral diameter (-4 +/- 1 mm), moved the anterior
      papillary muscle closer to the annulus (2 +/- 1 mm), and relieved posterior
      leaflet apical restriction (2 +/- 1 mm, P < .05 papillary muscle repositioning vs
      chronic ischemic mitral regurgitation) but did not change lateral posterior
      papillary muscle displacement or decrease mitral regurgitation (1.9 +/- 1.2).
      CONCLUSIONS: Septal-lateral annular cinching moved the lateral annulus and the
      posterior papillary muscle closer to the septum and reduced mitral regurgitation
      unlike posterior papillary muscle repositioning, and thus the key mitral
      subvalvular repair component must correct posterior papillary muscle lateral
      displacement.

PMID- 15942567
TI  - Procedure rates and outcomes of coronary revascularization procedures in
      California and New York.
AB  - OBJECTIVE: Background data were obtained on all California hospitals performing
      coronary artery bypass grafting and percutaneous coronary intervention procedures
      and compared with reports published by the state of New York to develop a
      collaborative quality improvement program for cardiac surgery programs. METHODS:
      The Patient Discharge Database of the Office of Statewide Health Planning and
      Development was queried for the years 1999-2001. In-hospital mortality and risk
      factors for coronary artery bypass grafting and percutaneous coronary
      intervention were obtained by using demographic data and International
      Classification of Diseases-Ninth Revision-Clinical Modification procedure and
      diagnosis codes. Risk models were developed by means of logistic regression
      analysis. RESULTS: Overall coronary artery bypass grafting mortality was 33%
      higher and percutaneous coronary intervention mortality was twice as high in
      California compared with that in New York. Procedural volume (per unit
      population) was higher in New York. In high-volume California hospitals (>300
      procedures per year), coronary artery bypass grafting mortality was similar
      (California, 2.42%; New York, 2.25%). Excess coronary artery bypass grafting
      mortality (>4.0%) occurred only in low-volume programs. Risk adjustment did not
      change the volume effect for coronary artery bypass grafting. No volume effect
      was noted for risk-adjusted percutaneous coronary intervention mortality. There
      were no obvious differences in risk factors between California and New York.
      Programs performing relatively fewer coronary artery bypass grafting procedures
      compared with percutaneous coronary interventions were found to have
      significantly higher coronary artery bypass grafting mortality after adjusting
      for volume effects. Percutaneous coronary intervention volume is increasing and
      coronary artery bypass grafting volume is decreasing in both California and New
      York. CONCLUSIONS: Excess coronary artery bypass grafting mortality in California
      is related to the large number of low-volume programs. Excess percutaneous
      coronary intervention mortality might be related to case selection or timing of
      intervention. A relationship between percutaneous coronary intervention volume
      and coronary artery bypass grafting mortality is suggested in which increasing
      percutaneous coronary intervention volume relative to coronary artery bypass
      grafting volume might have the effect of shifting patients with undefined higher
      risk characteristics to coronary artery bypass grafting.

PMID- 15942568
TI  - In the current era, complete revascularization improves survival after coronary
      artery bypass surgery.
AB  - BACKGROUND: Complete revascularization has been the standard for coronary bypass
      grafting. However, surgical intervention has evolved with increasing use of
      arterial conduits and off-pump techniques. METHODS: Patients undergoing non-redo
      bypass surgery from January 1998 through December 2000 were followed up with
      questionnaires and telephone contact. Incomplete revascularization was defined as
      absence of bypass grafts placed to a coronary territory supplied by a vessel with
      50% or greater stenosis. RESULTS: One thousand thirty-four patients were followed
      for a mean of 3.3 +/- 1.6 years. Complete revascularization was found in 937
      (90.6%) patients, and incomplete revascularization was found in 97 (9.4%)
      patients. Eight hundred twenty-seven (80.4%) patients underwent on-pump
      operations, and 207 (19.6%) underwent off-pump operations. Incomplete
      revascularization was more prevalent in off-pump versus on-pump operations (21.7%
      vs 6.3%, P < .001). Multivariable Cox regression analysis indicated that in
      hospital cerebrovascular accidents (hazard ratio, 5.49; P < .001), chronic
      obstructive pulmonary disease (hazard ratio, 1.97; P = .019), and incomplete
      revascularization (hazard ratio, 1.85; P = .040) predicted an increased hazard
      (risk) of cardiac death. Left internal thoracic artery (hazard ratio, 0.38; P =
      .047), right internal thoracic artery (hazard ratio, 0.25; P = .019), and radial
      artery (hazard ratio, 0.36; P < .001) grafting reduced the risk of cardiac death.
      The 5-year unadjusted survival rate was 52.6% versus 82.4% in patients undergoing
      incomplete and complete revascularization ( P < .001), with cardiac survival
      rates of 74.5% versus 93.1%, respectively ( P < .001). However, this difference
      in cardiac survival was smaller in octogenarians with incomplete versus complete
      revascularizations (77.4% vs 87.6%, P = .101) and was essentially absent in off
      pump versus on-pump operations if complete revascularization was achieved in both
      cases (93.6% vs 93.1%, P > .200). CONCLUSIONS: Complete revascularization and
      arterial grafting improve 5-year survival. Off-pump techniques do not affect
      survival. Complete revascularization should be performed whenever possible.

PMID- 15942569
TI  - Significant value of autopsy for quality management in cardiac surgery.
AB  - OBJECTIVE: With recent advances in diagnostic imaging, the value of autopsy has
      been called into question. The aim of our study was to assess the current impact
      of autopsy for early postoperative quality management in cardiac surgery.
      METHODS: Between 2000 and 2003, a total of 14,313 patients underwent cardiac
      surgery at our center. Of these, 898 patients (6.3%) died, and autopsy was
      performed in 468 cases (52.1%). Data from clinical and postmortem examination
      were prospectively analyzed regarding causes of death, postoperative
      complications, concomitant diseases, and surgery-associated pathologic findings.
      RESULTS: Mean age was 68.7 years. Mean survival was 13.9 postoperative days. On
      autopsy, causes of death were cardiac in 49.8% of cases (n = 233), respiratory in
      8.3% (n = 39), cerebral in 6.4% (n = 30), abdominal in 4.7% (n = 22), multiorgan
      failure or sepsis in 14.9% (n = 70), pulmonary embolism in 6.6% (n = 31),
      procedure associated in 8.3% (n = 39), and others in 0.9% (n = 4). Discrepancies
      between clinical and postmortem determinations of cause of death were found in
      108 cases (23.1%). These were acute myocardial infarction (n = 38), low cardiac
      output (n = 9), respiratory (n = 8), cerebral (n = 5), abdominal (n = 7),
      multiorgan failure or sepsis (n = 12), pulmonary embolism (n = 18), and procedure
      associated (11). Clinically unrecognized postoperative complications were found
      in 364 cases (77.8%). Unknown concomitant diseases were found in 464 cases
      (99.1%), with potential therapeutic relevance in 90 cases (19.2%). In 85 cases
      (18.2%), autopsy examination revealed 96 premortem unrecognized surgery
      associated pathologic findings. CONCLUSION: A high overall discrepancy rate
      between premortem and autopsy diagnoses was recognized. Autopsy revealed
      clinically relevant information in a significant number of cases. Therefore
      autopsy remains essential for quality assessment in perioperative treatment.

PMID- 15942570
TI  - Performance of bioprostheses and mechanical prostheses assessed by composites of
      valve-related complications to 15 years after mitral valve replacement.
AB  - OBJECTIVE: Predominant concerns of patients undergoing valve replacement surgery
      are risks of death, stroke, antithrombotic bleeding, and reoperation related to
      the replacement prosthesis. The purpose of this study was to compare valve
      related reoperation, morbidity (permanent impairment), and mortality between
      bioprostheses and mechanical prostheses for mitral valve replacement. METHODS:
      Between 1982 and 1998, a total of 959 bioprostheses were implanted in 943
      patients, and a total of 961 mechanical prostheses were implanted in 839
      patients. Total follow-ups were 5730 years for bioprostheses and 5271 years for
      mechanical prostheses. Eight variables were considered as predictors of risk for
      the composites of valve-related complications. RESULTS: The linearized occurrence
      rates for valve-related reoperation were 3.7 events/100 patient-years for
      bioprostheses and 0.5 events/100 patient-years for mechanical prostheses ( P <
      .001), with all age groups differentiated except older than 70 years. Valve
      related morbidity was undifferentiated for bioprostheses and mechanical
      prostheses. Valve-related mortalities were 1.7 events/100 patient-years for
      bioprostheses and 0.7 events/100 patient-years for mechanical prostheses ( P <
      .001). Predictors of valve-related reoperation were age and valve type. The only
      predictor of valve-related morbidity was age, whereas age and valve type were
      predictors for valve-related mortality. Actual freedom from valve-related
      reoperation favored mechanical prostheses in all age groups except older than 70
      years (91.7% +/- 2.0% for bioprostheses at 15 years and 96.7% +/- 1.5% at 12
      years for mechanical prostheses). Actual freedom from valve-related morbidity was
      not different between bioprostheses and mechanical prostheses. Actual freedom
      from valve-related mortality favored mechanical prostheses in all groups except
      older than 70 years. CONCLUSION: Comparative evaluation gives high priority in
      mitral valve replacement for mechanical prostheses relative to bioprostheses for
      freedom from valve-related reoperation and valve-related mortality but not valve
      related morbidity. Freedom from valve-related reoperation and valve-related
      mortality favors mechanical prostheses for all age groups except older than 70
      years. Valve-related morbidity, due to neurologic or functional impairments, does
      not differentiate between bioprostheses and mechanical prostheses.

PMID- 15942571
TI  - Does reporting of coronary artery bypass grafting from administrative databases
      accurately reflect actual clinical outcomes?
AB  - OBJECTIVES: Quality assessment of coronary artery bypass grafting has
      traditionally been performed with data from clinical databases. Administrative
      databases that rely primarily on information collected for billing purposes
      increasingly have been used as tools for public reporting of outcomes quality.
      The correlation of administrative data with clinical data for clinical quality
      assessment has not been confirmed. METHODS: With data from a clinical database,
      we analyzed the outcomes of all patients who underwent coronary artery bypass
      grafting surgery in 1 hospital between 1999 and 2001. This information was
      collected before, during, and after the surgery and hospitalization by designated
      clinical individuals involved with the patient's care and then entered into an
      audited clinical database (The Society of Thoracic Surgeons National Cardiac
      Database). These data were then compared with administrative data collected on
      the same cohort of patients for the number of procedures performed and mortality
      rate as reported by the federal government (Medical Provider Analysis and
      Review), state government (Texas Health Care Information Council), hospital
      system (HCA, Inc, Casemix Database), and an internet Web site (healthgrades.com).
      Data were analyzed on the basis of the population reported, definitions used,
      risk assessment algorithms, and case volumes. RESULTS: By using the audited The
      Society of Thoracic Surgeons database as the standard and aggregating the
      reporting of case volumes by the inclusion criteria of various sources of
      administrative data, we found variances in the reported procedure volumes and
      mortality. Case volumes were overreported by as much as 21% in all patients and
      underreported by up to 16% or more in Medicare patients. Mortality in
      administrative data exceeded that reported in clinical data by 21%. Reasons for
      variances included time period reported (calendar vs fiscal year), population
      reported (all patients, Medicare patients, Medicare patients aged >/= 65 years),
      date used for the patient record captured (date of surgery, discharge), and the
      definition of mortality. Different proprietary risk-adjusting algorithms used
      magnified variances with risk-adjusted mortality exceeding the Society of
      Thoracic Surgeons data by as much as 61%. CONCLUSIONS: Substantial variability of
      reported outcomes is seen in administrative data sets compared with an audited
      clinical database in the end points of the number of procedures performed and
      mortality. This variability makes it challenging for the nonclinician unfamiliar
      with outcomes analysis to make an informed decision.

PMID- 15942572
TI  - A validated simple model to predict coexistent coronary disease in patients
      undergoing mitral valve surgery.
AB  - OBJECTIVE: The primary limitation of the American Heart Association/American
      College of Cardiology guidelines is specificity. To improve the selection
      process, we proposed a simple additive model including age (1 point for every 5
      years above 50), male sex (2 points), hypercholesterolemia (2 points), angina (3
      points), and electrocardiographic evidence of ischemia (3 points). We recommend
      screening angiography at 3 or more points. This model was previously derived from
      359 patients at Papworth Hospital. METHODS: The validation cohort was a
      consecutive series of patients who underwent mitral valve surgery at the Royal
      Brompton Hospital. Preoperative coronary angiography reports were obtained, and
      coronary disease was defined as luminal narrowing of 50% in 2 or more views.
      Sensitivities and specificities were calculated for the American Heart
      Association/American College of Cardiology criteria, the simple additive model,
      and a logistic regression model. Receiver operating characteristic curves were
      used to validate accuracy and compare discrimination with logistic regression.
      RESULTS: From 1998 through 2003, angiographic details were available for 342
      (86%) of 396 patients who underwent mitral valve surgery. The sensitivity and
      specificity of the American Heart Association/American College of Cardiology
      guidelines were 100% and 5%, respectively; those of the simple additive model
      were 91% and 44%, respectively; and those of logistic regression were 93% and
      41%, respectively. The receiver operating characteristic areas for the simple
      additive and logistic regression model were 0.78 (95% confidence interval, 0.73
      0.84) and 0.80 (95% confidence interval, 0.74-0.85), respectively. CONCLUSIONS:
      This is the third independent cohort to highlight the poor specificity of the
      American Heart Association/American College of Cardiology guidelines. Although
      high sensitivity is achieved, the cost is the majority of patients requiring
      screening angiography. Our validated simple model improved the specificity and
      selection; however, this was achieved at the expense of decreased sensitivity.

PMID- 15942573
TI  - Surgical ablation of atrial fibrillation with bipolar radiofrequency as the
      primary modality.
AB  - OBJECTIVES: In studying cardiac surgical patients undergoing atrial fibrillation
      ablation with bipolar radiofrequency, we sought to (1) quantify the time-related
      prevalence of atrial fibrillation postoperatively and identify its risk factors
      and (2) determine time-related ablation failure and its risk factors. METHODS:
      From November 2001 to January 2004, 513 patients underwent atrial fibrillation
      ablation (bipolar radiofrequency alone or with cryothermy) and other cardiac
      operations. Rhythm documented on 3495 postoperative electrocardiograms was used
      to estimate the prevalence of and risk factors for atrial fibrillation across
      time. Ablation failure was defined as occurrence of atrial fibrillation any time
      beyond 6 months after operation. RESULTS: Prevalence of postoperative atrial
      fibrillation peaked at about 1 month, decreased to 13% at 6 months, and gradually
      increased thereafter. Risk factors associated with increased prevalence varied by
      time period and included older age ( P = .004) for early occurrence, lesion set
      in permanent atrial fibrillation ( P = .02) for late occurrence, and larger left
      atrial diameter ( P = .02) and permanent atrial fibrillation ( P < .0001) for
      occurrence across the entire time span. Freedom from ablation failure was 72% at
      12 months. Risk factors for ablation failure included lesion set in permanent
      atrial fibrillation ( P = .001), longer duration of atrial fibrillation ( P =
      .01), and larger left atrial diameter ( P = .03). CONCLUSIONS: Bipolar
      radiofrequency enables extension of ablation to most cardiac surgical patients
      with atrial fibrillation. Recurrence is influenced by the type and duration of
      atrial fibrillation, choice of lesion set in permanent atrial fibrillation, and
      left atrial size. Early operation, careful choice of lesion set, and left atrial
      reduction might enhance results.

PMID- 15942574
TI  - Midterm clinical result of tissue-engineered vascular autografts seeded with
      autologous bone marrow cells.
AB  - OBJECTIVE: Prosthetic and bioprosthetic materials currently in use lack growth
      potential and therefore must be repeatedly replaced in pediatric patients as they
      grow. Tissue engineering is a new discipline that offers the potential for
      creating replacement structures from autologous cells and biodegradable polymer
      scaffolds. In May 2000, we initiated clinical application of tissue-engineered
      vascular grafts seeded with cultured cells. However, cell culturing is time
      consuming, and xenoserum must be used. To overcome these disadvantages, we began
      to use bone marrow cells, readily available on the day of surgery, as a cell
      source. The aim of the study was to assess the safety and feasibility of this
      technique for creating vascular tissue under low-pressure systems such as
      pulmonary artery or venous pressure. METHODS: Since September 2001, tissue
      engineered grafts seeded with autologous bone marrow cells have been implanted in
      42 patients. The patients or their parents were fully informed and had given
      consent to the procedure. A 5-mL/kg specimen of bone marrow was aspirated with
      the patient under general anesthesia before the skin incision. The polymer tube
      serving as a scaffold for the cells was composed of a copolymer of l -lactide and
      -caprolactone (50:50). This copolymer is degraded by hydrolysis. The matrix is
      more than 80% porous, and the diameter of each pore is 20 to 100 microm.
      Polyglycolic acid woven fabric with a thickness of 0.5 mm was used for
      reinforcement. Twenty-three tissue-engineered conduits (grafts for extracardiac
      total cavopulmonary connection) and 19 tissue-engineered patches were used for
      the repair of congenital heart defects. The patients' ages ranged from 1 to 24
      years (median 5.5 years). All patients underwent a catheterization study,
      computed tomographic scan, or both, for evaluation after the operation. The
      patients received anticoagulation therapy for 3 to 6 months after surgery.
      RESULTS: Mean follow-up after surgery was 490 +/- 276 days (1.3-31.6 months,
      median 16.7 months). There were no complications such as thrombosis, stenosis, or
      obstruction of the tissue-engineered autografts. One late death at 3 months after
      total cavopulmonary connection was noted in patient with hypoplastic left heart
      syndrome; this was unrelated to the tissue-engineered graft function. There was
      no evidence of aneurysm formation or calcification on cineangiography or computed
      tomography. All tube grafts were patent, and the diameter of the tube graft
      increased with time (110% +/- 7 % of the implanted size). CONCLUSION:
      Biodegradable conduits or patches seeded with autologous bone marrow cells showed
      normal function (good patency to a maximum follow-up of 32 months). As living
      tissues, these vascular structures may have the potential for growth, repair, and
      remodeling. The tissue-engineering approach may provide an important alternative
      to the use of prosthetic materials in the field of pediatric cardiovascular
      surgery. Longer follow-up is necessary to confirm the durability of this
      approach.

PMID- 15942575
TI  - Trends in vascular ring surgery.
AB  - OBJECTIVE: We sought to review our experience with infants and children with
      anatomically complete vascular rings (ie, double aortic arch and right aortic
      arch with left ligamentum) and define perioperative trends in diagnostic imaging,
      operative techniques, and clinical outcomes. METHODS: From 1946 through 2003, 209
      patients (113 with double aortic arch and 96 with right aortic arch) underwent
      surgical repair. Mean and median ages at the time of the operation were as
      follows: double aortic arch, 1.4 +/- 2.4 years and 0.75 years, respectively;
      right aortic arch, 2.7 +/- 3.9 years and 0.9 years, respectively. Fourteen
      (14.6%) patients with right aortic arch had an associated Kommerell diverticulum.
      Cardiac diagnoses were present in 26 (12.4%) of 209 patients. RESULTS: There has
      been no operative mortality since 1959. In the past 30 years, mean hospital stay
      decreased from 8 to 3 days. Primary means of diagnosis has shifted from barium
      swallow and angiography to computed tomographic scanning or magnetic resonance
      imaging. In the past 10 years, 73% of patients had preoperative or intraoperative
      bronchoscopy. The technique of operation has shifted to a muscle-sparing left
      thoracotomy without routine chest drainage. In 7 recent patients with right
      aortic arch and a Kommerell diverticulum, the diverticulum was resected, and the
      left subclavian artery was transferred to the left carotid artery as a primary
      procedure. CONCLUSIONS: At our institution, computed tomographic scanning has
      replaced barium swallow as the diagnostic procedure of choice for vascular ring
      evaluation. We recommend both preoperative bronchoscopy and echocardiography. Use
      of a muscle-sparing thoracotomy without routine chest drainage has decreased mean
      hospital stay. For patients with a right aortic arch and associated Kommerell
      diverticulum, we recommend diverticulum resection with left subclavian artery
      transfer to the left carotid artery.

PMID- 15942576
TI  - Progression of liver pathology in patients undergoing the Fontan procedure:
      Chronic passive congestion, cardiac cirrhosis, hepatic adenoma, and
      hepatocellular carcinoma.
AB  - BACKGROUND: Staged palliative surgical procedures have been an effective
      treatment of complex congenital heart defects. The Fontan procedure has been of
      particular benefit to infants with functional single-ventricle complexes but with
      the consequence of a sustained increase of right-sided venous pressure. METHODS:
      We reviewed the clinical and pathologic features of 9 autopsied patients having
      undergone the Fontan procedure, with special attention given to their liver
      pathology. RESULTS: The 9 patients died from a few hours to 18 years after the
      Fontan operation. Chronic passive congestion was seen in 7 patients, and 4
      patients surviving 4 to 18 years also had cardiac cirrhosis. Hepatic adenoma in
      the setting of cardiac cirrhosis was found in a patient surviving for 9 years.
      One patient surviving for 18 years had hepatocellular carcinoma superimposed on
      cardiac cirrhosis. Rupture of the hepatoma in this case led to fatal hemorrhage.
      CONCLUSION: The study shows that chronically increased hepatic venous pressure
      from the Fontan procedure might lead to chronic passive congestion, cardiac
      cirrhosis, hepatic adenoma, and hepatocellular carcinoma.

PMID- 15942577
TI  - Need for closure of secundum atrial septal defect in infancy.
AB  - OBJECTIVES: Closure of isolated secundum atrial septal defect is generally
      recommended at the age of 4 to 5 years. However, there are children with isolated
      secundum atrial septal defect in whom early closure should be performed. We aimed
      to assess the underlying conditions that led to earlier closure in this special
      patient group and to analyze the outcome. METHODS AND RESULTS: From January 1990
      through August 2002, 24 infants with isolated secundum atrial septal defect
      underwent surgical closure within the first year of life. All children were
      symptomatic. Signs of pulmonary hyperperfusion, such as tachydyspnea, failure to
      thrive, recurrent respiratory infections, or heart failure, were present. Four
      infants required artificial ventilation. Ten patients had additional problems,
      such as prematurity with chronic lung disease, hepato-omphalocele and congenital
      diaphragmatic hernia, which were present in 1 patient each. Eleven patients had
      defined dysmorphic syndromes. All but 1 infant underwent preoperative invasive
      hemodynamic evaluation. Thirteen patients had pulmonary hypertension
      preoperatively. The follow-up time was 46 +/- 33 months (range, 4-125 months). At
      follow-up, pulmonary artery pressure proved to be normal in 11 of the 13 children
      who had pulmonary hypertension previously. One patient died of persistent
      pulmonary hypertension. Clinical performance, growth, and development improved in
      nearly all patients. All ventilator-dependent children could be weaned shortly
      after atrial septal defect closure. CONCLUSIONS: If lungs are compromised, even a
      minor left-to-right shunt might be poorly tolerated in infancy. In these children
      early surgical closure of an isolated secundum atrial septal defect should be
      performed to support thrive and growth and to prevent the onset of irreversible
      changes of the pulmonary vasculature.

PMID- 15942578
TI  - Surgically treated primary cardiac tumors in early infancy and childhood.
AB  - OBJECTIVE: Primary heart tumors in childhood are rare and mostly benign. Surgical
      treatment is advocated when symptoms or hemodynamic impairment is present.
      MATERIALS AND METHODS: Between 1986 and 2003, 8 children (3 males and 5 females,
      age ranging 5 days to 6.7 years, median 78 days) with a clinical diagnosis of
      cardiac mass were treated with surgery. Diagnosis was made by prenatal
      echocardiography in 3 patients and by 2-dimensional Doppler echocardiography in 5
      patients. RESULTS: Complete surgical excision of the cardiac mass was feasible in
      all but 1 patient who underwent orthotopic heart transplantation. Surgical
      pathology examination revealed myxoma in 2 patients, fibroma in 2 patients,
      rhabdomyoma in 2 patients (multiple in 1), hamartoma in 1 patient, and teratoma
      in 1 patient. One patient died of cerebral malignancy 38 months after cardiac
      transplantation. At a mean follow-up of 69.2 months (range 3-190 months), all the
      remaining patients are asymptomatic, with good ventricular function on 2
      dimensional echocardiography and no signs of residual or recurrent tumor.
      CONCLUSION: Surgical excision of obstructive cardiac tumors in childhood is
      safely feasible. Heart transplantation may represent the only therapeutic option
      when the tumor extensively invades the ventricular walls. Although 2-dimensional
      echocardiography remains a reliable diagnostic tool, a definite diagnosis of
      tumor histotype requires a thorough histopathologic characterization.

PMID- 15942579
TI  - Integrated computed tomography-positron emission tomography in patients with
      potentially resectable malignant pleural mesothelioma: Staging implications.
AB  - BACKGROUND: Integrated computed tomography-positron emission tomography imaging
      with coregistration of anatomic and functional imaging data may improve the
      accuracy of malignant pleural mesothelioma staging. We evaluate the use of
      integrated computed tomography-positron emission tomography in patients with
      malignant pleural mesothelioma who are being considered for extrapleural
      pneumonectomy. METHODS: Twenty-nine patients with malignant pleural mesothelioma
      who were judged to be candidates for extrapleural pneumonectomy after clinical
      and conventional radiologic evaluation underwent whole-body integrated computed
      tomography-positron emission tomography and pathologic staging. Two reviewers
      blinded to the results of clinical and pathologic staging retrospectively
      evaluated computed tomography, positron emission tomography, and coregistered
      computed tomography-positron emission tomography images. Staging was performed
      according to the International Mesothelioma Interest Group TNM staging system.
      Histopathology and/or results of further radiologic evaluation or follow-up
      served as the reference standard. RESULTS: Integrated computed tomography
      positron emission tomography provided additional information in 11 of 29 patients
      that precluded extrapleural pneumonectomy. The overall tumor stage was correctly
      classified in 21 of 29 patients. The tumor stage was correctly determined in 15
      of 24 patients, 6 of whom had T4 (nonresectable) disease. The node stage was
      accurately determined in 6 of 17 patients. Extrathoracic metastases not
      identified by routine clinical and conventional radiologic evaluation were
      detected in 7 of 29 patients and were found to be diffuse (n = 2) or solitary (n
      = 5). CONCLUSIONS: Integrated computed tomography-positron emission tomography
      increases the accuracy of malignant pleural mesothelioma staging and is important
      in determining the appropriate therapy in patients being considered for
      extrapleural pneumonectomy.

PMID- 15942580
TI  - Thermo-wrap technology preserves normothermia better than routine thermal care in
      patients undergoing off-pump coronary artery bypass and is associated with lower
      immune response and lesser myocardial damage.
AB  - OBJECTIVE: Perioperative hypothermia might be detrimental to the patient
      undergoing off-pump coronary artery bypass surgery. We assessed the efficacy of
      the Allon thermoregulation system (MTRE Advanced Technologies Ltd, Or-Akiva,
      Israel) compared with that of routine thermal care in maintaining normothermia
      during and after off-pump coronary artery bypass surgery. METHODS: Patients
      undergoing off-pump coronary artery bypass surgery were perioperatively and
      randomly warmed with the 2 techniques (n = 45 per group). Core temperature,
      hemodynamics, and troponin I, interleukin 6, interleukin 8, and interleukin 10
      blood levels were assessed. RESULTS: The mean temperature of the patients in the
      Allon thermoregulation system group (AT group) was significantly ( P < .005)
      higher than that of the patients receiving routine thermal care (the RTC group);
      less than 40% of the latter reached 36 degrees C compared with 100% of the
      former. The cardiac index was higher and the systemic vascular resistance was
      lower ( P < .05) by 16% and 25%, respectively, in the individuals in the AT group
      compared with in the individuals in the RTC group during the 4 postoperative
      hours. End-of-surgery interleukin 6 levels and 24-hour postoperative troponin I
      levels were significantly ( P < .01) lower in the patients in the AT group than
      in the RTC group. The RTC group's troponin levels closely correlated with their
      interleukin 6 levels at the end of the operation ( R = 0.51, P = .002).
      CONCLUSIONS: Unlike routine thermal care, the Allon thermoregulation system
      maintains core normothermia in more than 80% of patients undergoing off-pump
      coronary artery bypass surgery. Normothermia is associated with better cardiac
      and vascular conditions, a lower cardiac injury rate, and a lower inflammatory
      response. The close correlation between the increased interleukin 6 and troponin
      I levels in the routine thermal care group indicates a potential deleterious
      effect of lowered temperature on the patient's outcome.

PMID- 15942581
TI  - Long-term pulmonary function after thoracic sympathectomy.
AB  - BACKGROUND: The purpose of this study was to evaluate the long-term and midterm
      effects of thoracic sympathectomy on pulmonary function and to assess the
      influence of the sympathetic nervous system on bronchomotor tone. METHODS: Thirty
      seven consecutive patients were diagnosed with primary hyperhidrosis requiring
      thoracic sympathectomy and were included in this study. Spirometry and
      methacholine challenge testing were performed before and 3 months after surgery.
      To assess the long-term effects of the intervention, another spirometric study
      was performed 1 year later. RESULTS: Spirometry 3 months after surgery showed a
      significant decrease in the forced vital capacity (-5.2%), the forced expiratory
      volume in the first second (-6.1%), and the forced expiratory flow between 25%
      and 75% of vital capacity (-5.1%). Whereas methacholine challenge testing before
      surgery was positive in 3 subjects (2 of whom were asthmatic), it was positive in
      6 patients after the procedure; differences were not statistically significant.
      After 12 months, forced vital capacity started recovering, and forced expiratory
      volume in the first second and forced expiratory flow rate 25% to 75% showed a
      sustained and significant reduction (-2.8% and -11.2%, respectively); however,
      patients remained asymptomatic. CONCLUSIONS: We conclude that thoracic
      sympathectomy generates a mild, although significant, impairment of the
      bronchomotor tone, with no clinical consequences. These results suggest that the
      sympathetic nervous system is involved in pulmonary bronchomotor tone.

PMID- 15942582
TI  - Comparing the global mRNA expression profile of human atrial and ventricular
      myocardium with high-density oligonucleotide arrays.
AB  - OBJECTIVES: The knowledge of chamber-specific gene expression in human atrial and
      ventricular myocardium is essential for the understanding of myocardial function
      and the basis for the identification of putative therapeutic targets in the
      treatment of cardiac arrhythmia and heart failure. In this study the gene
      expression pattern of human left atrial and ventricular myocardium was analyzed.
      METHODS: Global mRNA expression patterns with high-density oligonucleotide arrays
      between left atrial and left ventricular myocardium of 6 patients with heart
      failure undergoing heart transplantation were compared. Clustering of microarray
      data confirmed chamber-specific gene expression profiles. Genes similarly
      expressed in all patients were further analyzed, and data were confirmed by means
      of real-time polymerase chain reaction and Western blot analysis. RESULTS: Of
      22,215 genes examined, 7115 transcripts were found to be expressed in all 12
      human myocardial samples. One hundred twenty-five genes were differentially
      expressed between left atrial and left ventricular specimens in all patients
      examined. Novel genes preferentially expressed in human atria were identified.
      Interestingly, several potassium channels of subfamily K are more highly
      expressed in atria than in ventricles. Members of the potassium inwardly
      rectifying channel of subfamily J were found to be more highly expressed in human
      ventricular myocardium. Finally, chronic atrial fibrillation was associated with
      reduced atrial expression of the potassium channel TWIK-1, suggesting potential
      contribution of the corresponding current to electrical remodeling. CONCLUSIONS:
      Human atria and ventricles show specific gene expression profiles. Our data
      provide the basis of a comprehensive understanding of chamber-specific gene
      expression in diseased human hearts and will support the identification of
      therapeutic targets in the treatment of arrhythmia and heart failure.

PMID- 15942583
TI  - Assessment of hemostatic activation during cardiopulmonary bypass for coronary
      artery bypass grafting with bivalirudin: results of a pilot study.
AB  - OBJECTIVE: Bivalirudin has been successfully used as a replacement for heparin
      during on-pump coronary artery bypass grafting. This study was conducted to
      assess the effects of the currently suggested protocol for bivalirudin on
      hemostatic activation during cardiopulmonary bypass with and without cardiotomy
      suction. METHODS: Ten patients scheduled for coronary artery bypass grafting were
      enrolled. Bivalirudin was given with a bolus of 50 mg in the priming solution and
      1.0 mg/kg for the patient, followed by an infusion of 2.5 mg . kg(-1) . h(-1)
      until 15 minutes before the conclusion of cardiopulmonary bypass. Cardiopulmonary
      bypass was performed with a closed system in 5 patients with and in 5 patients
      without the use of cardiotomy suction. Blood samples were obtained before and
      after cardiopulmonary bypass. D-dimers, fibrinopeptide A, prothrombin 1 and 2
      fragments, thrombin-antithrombin, and factor XIIa were determined. RESULTS:
      Values for factor XIIa remained almost unchanged in both groups, indicating a
      minor effect of contact activation. In patients without cardiotomy suction, post
      cardiopulmonary bypass values for D-dimers, fibrinopeptide A, prothrombin 1 and 2
      fragments, and thrombin-antithrombin were not significantly increased compared
      with pre-cardiopulmonary bypass values. In patients with cardiotomy suction,
      values obtained for these parameters had significantly increased compared with
      pre-cardiopulmonary bypass values and the values obtained in the group without
      cardiotomy suction after cardiopulmonary bypass. CONCLUSIONS: With this protocol,
      hemostatic activation during cardiopulmonary bypass was almost completely
      attenuated when cardiotomy suction was avoided. Cardiotomy suction results in
      considerable activation of the coagulation system and should therefore be
      restricted and replaced by cell saving whenever possible.

PMID- 15942584
TI  - Robotic mitral valve surgery: a United States multicenter trial.
AB  - OBJECTIVE: In a prospective phase II Food and Drug Administration trial, robotic
      mitral valve repairs were performed in 112 patients at 10 centers by using the da
      Vinci surgical system. The safety of performing valve repairs with computerized
      telemanipulation was studied. METHODS: After institutional review board approval,
      informed consent was obtained. Patients had moderate to severe mitral
      regurgitation. Operative technique included peripheral cardiopulmonary bypass, a
      4- to 5-cm right minithoracotomy, a transthoracic aortic crossclamp, and
      antegrade cardioplegia. The successful study end point was grade 0 or 1 mitral
      regurgitation by transthoracic echocardiography at 1 month after surgery.
      RESULTS: Valve repairs included quadrangular resections, sliding plasties, edge
      to-edge approximations, and both chordal transfers and replacements. The average
      age was 56.4 +/- 0.09 years (mean +/- SEM). There were 77 (68.8%) men and 35
      (31.2%) women. Valve pathology was myxomatous degeneration in 105 (91.1%), and
      103 (92.0%) had type II leaflet prolapse. Leaflet repair times averaged 36.7 +/-
      0.2 minutes, with annuloplasty times of 39.6 +/- 0.1 minutes. Total robot, aortic
      crossclamp, and cardiopulmonary bypass times were 77.9 +/- 0.3 minutes, 2.1 +/-
      0.1 hours, and 2.8 +/- 0.1 hours, respectively. On 1-month transthoracic
      echocardiography, 9 (8.0%) had grade 2 mitral regurgitation, and 6 (5.4%) of
      these had reoperations (5 replacements and 1 repair). There were no deaths,
      strokes, or device-related complications. CONCLUSIONS: Multiple surgical teams
      performed robotic mitral valve repairs safely early in development of this
      procedure, with a reoperation rate of 5.4%. Advancements in robotic design and
      adjunctive technologies may help in the evolution of this minimally invasive
      technique by decreasing operative times.

PMID- 15942585
TI  - Modulation of phosphatidylinositol 3-kinase signaling reduces intimal hyperplasia
      in aortocoronary saphenous vein grafts.
AB  - OBJECTIVES: Fifty percent of human aortocoronary saphenous vein grafts are
      occluded after 10 years. Intimal hyperplasia is an initial step in graft
      occlusion and consists of vascular smooth muscle cell proliferation.
      Phosphatidylinositol 3-kinase and its downstream regulator, the inositol 3
      phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), are
      important regulators of vascular smooth muscle cell proliferation, migration, and
      cell death. This study tests whether overexpression of PTEN in aortocoronary
      saphenous vein grafts can reduce intimal hyperplasia. METHODS: Adult dogs
      underwent aortocoronary bypass grafting to the left anterior descending artery by
      using the autologous saphenous vein. Saphenous vein grafts were treated with
      phosphate-buffered saline (n = 9), empty adenovirus (n = 8), or adenovirus
      encoding for PTEN (n = 8). Arteriography at 30 and 90 days assessed saphenous
      vein graft patency. A subset received saphenous vein grafts treated with a marker
      transgene (beta-galactosidase, n = 3), empty adenovirus (n = 4), or adenovirus
      encoding for PTEN (n = 4) and were killed on postoperative day 3 to confirm
      expression. Vascular smooth muscle cells were isolated from canine saphenous vein
      infected with adenovirus encoding for PTEN, and immunoblotting and proliferation
      assays were performed. RESULTS: Saphenous vein graft transgene expression was
      confirmed by means of immunohistochemistry, immunoblotting, and polymerase chain
      reaction. Arteriograms revealed all saphenous vein grafts to be patent. Saphenous
      vein grafts treated with adenovirus encoding for PTEN demonstrated reduced
      intimal area compared with those treated with empty adenovirus and phosphate
      buffered saline (1.39 +/- 0.11 vs 2.35 +/- 0.3 and 2.57 +/- 0.4 mm 2 , P < .05),
      and the intima/media ratio was lower in saphenous vein grafts treated with
      adenovirus encoding for PTEN (0.50 +/- 0.05 vs 1.43 +/- 0.18 and 1.11 +/- 0.14, P
      < .005). PTEN overexpression in vascular smooth muscle cells inhibited platelet
      derived growth factor-induced phosphorylation of Akt, a downstream effector of
      phosphatidylinositol 3-kinase. PTEN-treated vascular smooth muscle cells
      demonstrated decreased basal, platelet-derived growth factor-stimulated, and
      serum-stimulated proliferation. CONCLUSION: This study demonstrates that PTEN
      overexpression in aortocoronary saphenous vein grafts reduces intimal
      hyperplasia. The mechanism of this antiproliferative effect in vascular smooth
      muscle cells is likely due to inhibition of phosphatidylinositol 3-kinase
      signaling through Akt, with resultant decreases in vascular smooth muscle cell
      growth and survival. Therefore modulation of the phosphatidylinositol 3-kinase
      pathway through PTEN overexpression might represent a novel therapy to prevent
      saphenous vein graft intimal hyperplasia after coronary artery bypass grafting.

PMID- 15942586
TI  - Normalization of coronary microvascular reactivity and improvement in myocardial
      perfusion by surgical vascular endothelial growth factor therapy combined with
      oral supplementation of l-arginine in a porcine model of endothelial dysfunction.
AB  - OBJECTIVE: Vascular endothelial growth factor acts in part through nitric oxide
      release, the availability of which is decreased in endothelial dysfunction
      associated with advanced coronary artery disease. This could explain the
      relatively disappointing results of vascular endothelial growth factor therapy in
      clinical studies compared with animal studies. We examined the influence of L
      arginine supplementation to vascular endothelial growth factor therapy on
      myocardial microvascular reactivity and perfusion in a porcine model of
      endothelial dysfunction. METHODS: Twenty-four pigs were fed either a normal
      (NORM, n = 8) or high-cholesterol diet with (CHOL-ARG, n = 8) or without (CHOL, n
      = 8) L-arginine. All pigs underwent ameroid placement on the circumflex artery
      and then 3 weeks later received surgical vascular endothelial growth factor
      treatment. Four weeks after treatment, endothelial-dependent coronary
      microvascular responses and lateral myocardial perfusion were assessed.
      Endothelial cell density was determined by means of immunohistochemistry.
      Vascular endothelial growth factor, endothelial nitric oxide synthase, and Akt
      levels were determined by means of immunoblotting. RESULTS: Pigs from the CHOL
      group showed endothelial dysfunction in the circumflex territory, which was
      normalized by L-arginine supplementation. Vascular endothelial growth factor
      treatment was ineffective in the CHOL group (circumflex/left anterior descending
      coronary artery blood flow ratios: 0.95 [rest] and 0.74 [pace] before-after
      treatment; P < .05 compared with the NORM group). Addition of L-arginine restored
      the angiogenic effect of vascular endothelial growth factor (ratios: 1.13 [rest]
      and 1.20 [pace]; P < .05) and was associated with increased endothelial cell
      density, as well as vascular endothelial growth factor, endothelial nitric oxide
      synthase, and Akt protein levels in the ischemic territory. CONCLUSIONS: L
      Arginine supplementation can restore normal endothelium-dependent vasorelaxation
      and angiogenic response to vascular endothelial growth factor in a swine model of
      chronic myocardial ischemia with hypercholesterolemia-induced endothelial
      dysfunction. These findings suggest a putative role for L-arginine in combination
      with vascular endothelial growth factor therapy for end-stage coronary artery
      disease.

PMID- 15942587
TI  - Primary graft dysfunction and other selected complications of lung
      transplantation: A single-center experience of 983 patients.
AB  - OBJECTIVES: We sought to review the incidence and outcome of lung transplantation
      complications observed over 15 years at a single center. METHODS: We performed a
      retrospective review from our databases, tracking outcomes after adult and
      pediatric lung transplantation. The 983 operations between July 1988 and
      September 2003 included 277 pediatric and 706 adult recipients. Bilateral (74%),
      unilateral (19%), and living lobar transplants (4%) comprised the bulk of this
      experience. Retransplantations accounted for 44 (4.5%) of the operations.
      RESULTS: The groups differed by indication for transplantation. The adults
      included 57% with emphysema and 17% with cystic fibrosis, and the children
      included no patients with emphysema and 50% with cystic fibrosis. Hospital
      mortality was 96 (9.8%) of 983, including 46 (17%) of 277 of the children and 50
      (7%) of 706 of the adults. The overall survival curves did not differ between
      adults and children ( P = .56). Freedom from bronchiolitis obliterans syndrome at
      5 and 10 years was 45% and 18% for adults and 48% and 30% for children,
      respectively ( P = .53). The causes of death for adults included bronchiolitis
      obliterans syndrome (40%), respiratory failure (17%), and infection (14%),
      whereas the causes of death in children included bronchiolitis obliterans
      syndrome (35%), infection (28%), and respiratory failure (21%) ( P < .01).
      Posttransplantation lymphoproliferative disease occurred in 12% of pediatric
      recipients and 6% of adults ( P < .01). The frequency of treated airway
      complications did not differ between adults and children (9% vs 11%, P = .48).
      The frequency of primary graft dysfunction did not differ between children (22%)
      and adults (23%), despite disparity in the use of cardiopulmonary bypass.
      CONCLUSION: These results highlight major complications after lung
      transplantation. Despite differences in underlying diagnoses and operative
      techniques, the 2 cohorts of patients experienced remarkably similar outcomes.

PMID- 15942588
TI  - Lessons from the first patient to undergo full aortic root replacement using a
      homograft: a 29-year follow-up.

PMID- 15942589
TI  - Hemoptysis caused by saphenous vein graft aneurysm late after coronary artery
      bypass grafting.

PMID- 15942590
TI  - Infrarenal abdominal aortic aneurysm rupture and severe symptomatic coronary
      artery disease: Rapid combined transdiaphragmatic off-pump coronary surgery and
      abdominal aortic aneurysm repair.

PMID- 15942591
TI  - Multistep endobronchial-endovascular approach in recurrent acute respiratory
      failure caused by thoracic aneurysm.

PMID- 15942592
TI  - Caseous calcification of the mitral annulus.

PMID- 15942593
TI  - Giant metastatic myxoid liposarcoma of the mediastinum: a case report.

PMID- 15942594
TI  - Mechanical aortic valve malfunction: an intraoperative BioGlue complication.

PMID- 15942595
TI  - Complete surgical excision of a huge left ventricular fibroma.

PMID- 15942596
TI  - Acute leaflet arrest in St Jude Medical Regent aortic valve.

PMID- 15942597
TI  - Hemoptysis after CardioSEAL device embolization of a venous collateral after the
      Fontan operation.

PMID- 15942598
TI  - Tetralogy of Fallot and hypoplastic aortic arch: a novel perspective.

PMID- 15942599
TI  - Novel management strategy for severe cyanosis after Sano modification of the
      Norwood procedure.

PMID- 15942600
TI  - Long-term survival of a patient with tetralogy of Fallot after intracardiac
      palliation in the pre-pump era.

PMID- 15942601
TI  - Triangular retractor facilitates minimally invasive lobectomy.

PMID- 15942602
TI  - Successful subtotal tracheal replacement (using a skin/omental graft) for
      dehiscence after a resection for thyroid cancer.

PMID- 15942603
TI  - Esophagectomy and splenectomy in a patient with osteopetrosis.

PMID- 15942604
TI  - A case of pulmonary sequestration with Aspergillus species infection presenting
      as an enlarged right paratracheal mass.

PMID- 15942605
TI  - Caution with twisted arterial grafts.

PMID- 15942606
TI  - Effect of right anterolateral thoracotomy on breast development and scoliosis.

PMID- 15942607
TI  - Basic principles in impression making. 1952.

PMID- 15942608
TI  - Using transitional implants as fixation screws to stabilize a surgical template
      for accurate implant placement: a clinical report.
AB  - This article describes a method of using transitional implants as surgical
      fixation screws to orient a surgical template predictably during the placement of
      implants in the anterior mandible for an implant-supported bar-retained
      overdenture. Ridge reduction, transitional implant placement, implant placement,
      and removal of the transitional implants were completed in a single surgical
      appointment. Details of the template fabrication, incorporating transitional
      implants and surgical techniques, are described.

PMID- 15942609
TI  - Achieving immediate function with provisional prostheses after implant placement:
      a clinical report.
AB  - When using a conventional implant treatment protocol in edentulous patients,
      reduced function and comfort for up to 6 months after implant surgery is
      inevitable until bone healing is complete and a prosthesis is securely attached
      to the implants. The following report highlights 2 treatment modalities that
      enable immediate function by inserting provisional prostheses immediately after
      implant placement.

PMID- 15942610
TI  - The application of alveolar distraction osteogenesis following nonresorbable
      hydroxyapatite grafting in the anterior maxilla: a clinical report.
AB  - Distraction osteogenesis is a method of increasing bone length through the
      application of slow, controlled force on bone segments where periosteum and
      medullary blood supply are maintained. Recently, the procedure has been adapted
      to alveolar augmentation prior to prosthodontic rehabilitation. This report
      describes the use of alveolar distraction in the anterior maxilla and presents,
      to the authors' knowledge, the first reported successful application of the
      technique following nonresorbable hydroxyapatite grafting.

PMID- 15942611
TI  - Effects of Bartter's syndrome on dentition and dental treatment: a clinical
      report.
AB  - Bartter's syndrome is an autosomal recessive form of severe volume depletion due
      to renal salt wasting. This clinical report describes the prosthodontic treatment
      for a 24-year-old man who suffers from Bartter's syndrome. The treatment plan
      included endodontic treatment of the maxillary anterior incisors and placement of
      cast dowel-and-core restorations because of reduced crown height. The patient's
      remaining teeth were restored with metal-ceramic crowns.

PMID- 15942612
TI  - Direct restorative treatment of peg-shaped maxillary lateral incisors with resin
      composite: a clinical report.
AB  - This clinical report describes a treatment approach for esthetically restoring
      peg-shaped lateral incisors. Four patients with peg-shaped lateral incisors were
      restored with direct resin composite laminate veneers.

PMID- 15942613
TI  - Accuracy of newly formulated fast-setting elastomeric impression materials.
AB  - STATEMENT OF PROBLEM: Elastomeric impression materials have been reformulated to
      achieve a faster set. The accuracy of fast-setting elastomeric impression
      materials should be confirmed, particularly with respect to disinfection.
      PURPOSE: The purpose of this study was to assess the accuracy of 2 types of fast
      setting impression materials when disinfected with acid glutaraldehyde. MATERIAL
      AND METHODS: Impressions of the mandibular arch of a modified dentoform master
      model were made, from which gypsum working casts and dies were formed.
      Measurements of the master model and working casts included anteroposterior (AP)
      and cross-arch (CA) dimensions. A stainless steel circular crown preparation
      incorporated within the master model was measured in buccolingual (BL),
      mesiodistal (MD), and occlusogingival (OG) dimensions and compared to
      measurements from recovered gypsum dies. The impression materials examined were a
      fast-set vinyl polysiloxane (VPS-FS, Aquasil Ultra Fast Set), a fast-set
      polyether (PE-FS, Impregum Penta Soft Quick Step), and a regular-setting
      polyether as a control (PE, Impregum Penta). Disinfection involved immersion in
      3.5% acid glutaraldehyde (Banicide Advanced) for 20 minutes, and nondisinfected
      impressions served as a control. Linear measurements were made with a measuring
      microscope. Statistical analysis utilized a 2-way and single-factor analysis of
      variance with pair-wise comparison of mean values when appropriate. Hypothesis
      testing was conducted at alpha = .05 RESULTS: No differences were shown between
      the disinfected and nondisinfected conditions for all locations. However, there
      were statistical differences among the 3 materials for AP, CA, MD, and OG
      dimensions. AP and CA dimensions of all working casts were larger than the master
      model. Impressions produced oval-shaped working dies for all impression
      materials. PE and PE-FS working dies were larger in all dimensions compared to
      the stainless steel preparation, whereas VPS-FS-generated working dies were
      reduced in OG and MD dimensions. Differences detected were small and may not be
      of clinical significance. CONCLUSIONS: Impression material accuracy was
      unaffected by immersion disinfection. The working casts and dies were similar for
      PE and PE-FS. VPS-FS generated gypsum dies that were smaller in 2 of the 3
      dimensions measured and may require additional die relief. Overall accuracy was
      acceptable for all 3 impression materials.

PMID- 15942614
TI  - Type IV gypsum compatibility with five addition-reaction silicone impression
      materials.
AB  - STATEMENT OF PROBLEM: The compatibility of current addition-reaction silicone
      impression materials and Type IV gypsum products is not completely understood.
      PURPOSE: The purpose of this study was to compare surface detail reproduction
      between various combinations of contemporary addition-reaction silicone
      impression materials and Type IV gypsum products. MATERIAL AND METHODS: Under
      standardized conditions, 300 impressions were made of a ruled stainless steel die
      (ADA specification 19), using 5 addition-reaction silicones (Examix-NDS, Doric-ES
      Flo-Light, Panasil Contact Plus, Extrude Wash, and President Plus Jet). Fifteen
      impressions of each material were poured with each Type IV gypsum product (Silky
      Rock, Fuji Rock, Suprastone, or Vel-Mix). Using x12 magnification, 2 independent
      examiners scored the reproducibility of a 20-microm line in both the impression
      and the resultant casts. Statistical analysis was performed using 2-way analysis
      of variance and post hoc Bonferroni testing (alpha = .05). RESULTS: All
      impression materials tested fully reproduced the 20-microm line. Different
      impression materials showed different compatibility with different Type IV gypsum
      products. Only 25% of the Type IV gypsum casts completely reproduced the
      resultant 20-microm line with fine margins, and 88% of the completely reproduced
      casts were made from Suprastone. CONCLUSION: Not all combinations of impression
      material and Type IV gypsum products used exhibited similar compatibility.

PMID- 15942615
TI  - Influence of a 3-step tooth disinfection procedure on dentin bond strength.
AB  - STATEMENT OF PROBLEM: Clinicians have used disinfection materials to remove
      surface contaminants during cavity preparation. It has been postulated that
      disinfection materials may negatively affect shear bond strength of restorative
      materials. If so, large numbers of restorations may be predestined for early
      failure with the use of a disinfection protocol. PURPOSE: The purpose of this
      study was to determine whether there is a difference in the bond strength between
      dentin and resin composite with a 3-step disinfection technique compared to a
      conventional bonding technique without the additional disinfection protocol.
      MATERIAL AND METHODS: Sixty human molar teeth were sectioned parallel to the
      occlusal surface to expose mid-coronal dentin and mounted parallel to a bond
      shearing device on a universal testing machine and divided into 2 groups. In the
      3-step disinfection group (n = 30), specimens were treated with chlorhexidine,
      Tubulicid red, and sodium hypochlorite before dentin bonding, following the
      manufacturer's instructions for All Bond 2. In the control group (n = 30),
      specimens were treated only with the bonding protocol of All Bond 2. To ensure a
      uniform bond surface area, core paste was syringed into a cylindrical mold (2.38
      mm diameter and 2.00-mm height) that was in contact with the dentin bonding
      surface of each specimen and allowed to polymerize under constant force. All
      specimens were subjected to fracture by shear loading in a universal testing
      machine at a uniform crosshead speed of 0.05 mm per minute and expressed as MPa.
      Statistical analysis was performed using the Student t test (alpha = .05). The
      mode of failure was noted after a visual examination using a light microscope
      under x30 magnification. Failures were recorded as adhesive, cohesive or mixed,
      and statistical analysis was performed using a chi-square of homogeneity (alpha =
      .05). RESULTS: A significantly higher shear bond strength was found for the 3
      step disinfection group (mean shear bond strength, 25.3 +/- 4.6 MPa) compared to
      the control group (mean shear bond strength, 20.5 +/- 3.4 MPa) (P < .0001). Most
      failures were adhesive for the control group, but the fracture modes were evenly
      divided for the 3-step disinfection protocol group. A chi-square test of
      homogeneity showed a value of 12.3, df = 2, P = .0012. CONCLUSIONS: The 3-step
      disinfection technique group showed a significantly stronger dentin shear bond
      strength compared to the conventional bonding technique without disinfection.

PMID- 15942616
TI  - In vitro retentive strength of zirconium oxide ceramic crowns using different
      luting agents.
AB  - STATEMENT OF PROBLEM: In contrast to gold crowns, in vitro determination of the
      retentive strength of all-ceramic crowns is more difficult because components
      allowing connection to testing apparatus are not as easily integrated into the
      all-ceramic material. Nevertheless, retentive strength data are crucial for
      obtaining information about the potential clinical performance of luting cements
      for all-ceramic restorations. Therefore, a new in vitro model was necessary to
      evaluate the retentive strength of all-ceramic crowns. PURPOSE: The purpose of
      this in vitro study was to determine the retentive strength of 4 resin-cement
      systems, a compomer, a glass-ionomer cement, a resin-modified glass-ionomer
      cement, and a self-adhesive resin for luting zirconium oxide ceramic crowns.
      MATERIAL AND METHODS: One-hundred-twenty extracted human teeth were randomly
      divided into 12 groups (n = 10) and prepared in a standardized manner (5-degree
      taper, 3-mm occlusogingival height). All-ceramic crowns (Lava) were fabricated in
      a standardized manner for each tooth. The following cements and corresponding
      bonding regimens were used to lute the crowns to the teeth according to
      manufacturers' recommendations: CO, Compolute/EBS Multi; CO/RT, Compolute/EBS
      Multi/Rocatec; CB, Superbond C and B; CB/RT, Superbond C and B/Rocatec; CB/PL,
      Superbond C&B/Porcelain Liner M; PA, Panavia F; DC, Dyract Cem Plus/Xeno III;
      CH/PL, Chemiace II/Porcelain Liner M; RL, RelyX Luting, K/C, Ketac Cem/Ketac
      Conditioner; K, Ketac Cem; and RU, RelyX Unicem. After thermal cycling (5000
      cycles, 5 degrees C-55 degrees C), the outer surfaces of the cemented zirconium
      oxide ceramic crowns were treated (Rocatec) to improve bonding and then placed
      into a low-shrinkage epoxy resin block (Paladur). The block/crown and tooth
      components for each specimen were connected to opposing ends of a universal
      testing machine so that crown retention could be measured. Crowns were removed
      from teeth along their path of insertion. The retentive surface area (mm 2 ) was
      determined individually for each tooth. Statistical analyses were performed using
      the Wilcoxon exact test, (alpha =.05) and a Bonferroni correction (alpha =.001).
      RESULTS: The median (minimum/maximum) retentive strength values (MPa) were as
      follows: CO, 1.7 (0.6/4.3); CO/RT, 3.0 (1.3/5.4); CB, 4.8 (3.7/7.9); CB/RT, 8.1
      (4.2/12.7); CB/PL, 5.3 (3.7/10.2); PA, 4.0 (3.3/5.1); DC, 3.3 (2.1/5.6); CH/PL,
      4.0 (1.3/6.3); RL, 4.7 (2.8/6.6); K/C, 1.8 (0.6/2.3); K, 1.9 (0.2/4.5); and RU,
      4.8 (2.5/6.7). Superbond C&B (+ Rocatec) specimens showed the highest median
      retentive strength, but were not significantly different from Superbond C&B
      without Rocatec pretreatment of the all-ceramic crown's inner surface. Compolute
      specimens also did not benefit significantly from the Rocatec pretreatment.
      Within the materials used without pretreatment of the ceramic, Superbond C&B,
      Panavia, Dyract Cem Plus, RelyX Luting, and RelyX Unicem showed the highest
      median retentive strength values and were not significantly different.
      CONCLUSION: Within the conditions of this study, the compomer-cement, the resin
      modified glass-ionomer cement, and the self-adhesive resin luting agent had the
      same level of retentive quality as the resin luting agents, Superbond C&B, and
      Panavia. Rocatec pretreatment of the ceramic surface did not improve the
      retentive strengths of Compolute and Superbond C&B.

PMID- 15942617
TI  - The prosthodontic concept of crown-to-root ratio: a review of the literature.
AB  - Crown-to-root ratio is intended to serve as an aid in predicting the prognosis of
      teeth. However, controversy persists as to its impact on diagnosis and treatment
      planning. This article critically reviews the available literature on the crown
      to-root ratio assessment and criteria for evaluation of abutment use of
      periodontally compromised teeth. A Medline search was completed for the time
      period from 1966 to 2003, along with a manual search, to locate relevant peer
      reviewed articles and textbooks published in English. Key words used were "crown
      to-root ratio," "periodontal compromised dentition," "mobility," and
      "biomechanics." There was a dearth of evidence-based research on the topic.
      Although the use of the crown-to-root ratio in addition to other clinical indices
      may offer the best clinical predictors, no definitive recommendations could be
      ascertained.

PMID- 15942618
TI  - In vitro evaluation of microleakage of indirect composite inlays cemented with
      four luting agents.
AB  - STATEMENT OF PROBLEM: Microleakage around dental restorations is implicated in
      the occurrence of secondary carious lesions, adverse pulpal response, and reduced
      restoration longevity. PURPOSE: The aim of this in vitro study was to evaluate
      the microleakage of indirect resin composite inlays cemented with 4 luting
      agents. MATERIAL AND METHODS: Standardized Class V inlay preparations overlapping
      the cemento-enamel junction were prepared on the buccal and lingual surfaces of
      40 extracted human mandibular third molars. Eighty postpolymerized, heat-treated
      resin composite inlays (Targis, 72 specimens, 8 controls) were processed in stone
      replicas and cemented into the preparations using 4 luting agents (n = 18 + 2
      controls for each cement group): a resin composite used with a bonding agent
      (Variolink II/Excite), a resin composite used with a self-etching primer, but
      without bonding agent (Panavia F/ED Primer), a modified resin composite used with
      a bonding agent (Resinomer/One Step), and a resin-modified glass-ionomer cement
      (Fuji Plus). Thirty-six inlays (n = 9 + 1 control) were subjected to thermal
      cycling (2000 cycles, 5 degrees C/55 degrees C), whereas the other 36 were not.
      All the teeth were then immersed in 1% methylene blue dye solution for 48 hours.
      Microleakage score, margin location (enamel/cementum), thermal cycling history,
      and preparation location (buccal/lingual) were analyzed using a multivariate
      model (alpha = .05). Multivariate analysis was performed using a polychotomous
      logistic regression. RESULTS: The preparation location had no significant effect
      on dye penetration. The margin location (enamel or cementum) and the thermal
      cycling had a significant effect on microleakage (odds ratios [ORs] = 17.6 and
      8.04, respectively). In comparing the 3 resin-based luting agents (Variolink II,
      Panavia F, and Resinomer) to Fuji Plus, Panavia F exhibited the lowest
      significant overall microleakage (OR = 0.09), followed by Variolink II
      (significant OR equal to 0.43), whereas Resinomer demonstrated the greatest
      significant overall microleakage (OR = 1.35). CONCLUSION: Within the experimental
      conditions of this in vitro study, thermal cycling significantly increased
      microleakage (OR = 8.04). The overall microleakage at the enamel margins was
      significantly lower than the overall microleakage at the cementum margins for the
      4 luting agents tested (OR = 17.6).

PMID- 15942619
TI  - Long-term monitoring of microleakage of different amalgams with different liners.
AB  - STATEMENT OF PROBLEM: Microleakage is a major factor contributing to the
      occurrence of secondary caries around amalgam restorations. Purpose The purpose
      of this study was to evaluate the effect of amalgam type, liner type, and storage
      period on microleakage. MATERIAL AND METHODS: Two hundred seventy bovine incisors
      were divided into 18 groups (n = 15). Two high-copper amalgam alloys (admixed and
      spherical type) and 3 liner options (no liner, varnish, and adhesive) were used
      to restore Class V preparations. After placement of restorations, the teeth were
      stored for 3 different periods (1 day, 1 week, and 12 months) in saline solution,
      After storage, the specimens were immersed in 0.5% methylene blue for 24 hours,
      sectioned, and then mean depth of dye penetration was measured separately for the
      incisal and cervical areas with the use of a binocular microscope (x200). Scores
      were assigned to a millimeter scale (+/- 0.2 mm). The data were analyzed with a 3
      way analysis of variance and the Tukey Honestly Significant Different test (alpha
      = .05). RESULTS: The 3-way interaction was significant (P < .001 for the cervical
      and occlusal margins). After short-term storage (1 day and 1 week), the admixed
      alloy showed significantly lower leakage values than the spherical alloy only in
      cervical margins (1.45 and 1.56 for the admixed and 1.62 and 1.50 for the
      spherical alloy at the cervical [P = .034] and incisal margins [P = .702]),
      respectively. After 12 months, values decreased significantly for both amalgams,
      which were similar and lower than for the short-term storage period (short-term
      values of 1.62 and 1.39 for the admixed and 1.69 and 1.46 for the spherical alloy
      at the cervical and incisal margins, respectively; long-term values of 0.22 and
      0.20 for the admixed and 0.33 and 0.36 for the spherical alloy at the cervical
      and incisal margins, respectively [P < .019]). When the adhesive was used,
      significantly superior sealing was observed for both amalgams. For the no liner
      and cavity varnish groups, the admixed alloy showed superior performance compared
      to the spherical alloy (with no liner, 1.11 and 0.98 for the admixed and 0.83 and
      1.08 for the spherical alloy at the cervical and incisal margins, respectively;
      with varnish, 1.19 and 1.22 for the admixed and 1.63 and 1.34 for the spherical
      alloy, at the cervical and incisal margins, respectively [P < .037]). CONCLUSION:
      In the short-term, the lowest degree of leakage was found when adhesive was used.
      After 1 year, no differences were detected, regardless of the amalgam type and
      liner used.

PMID- 15942620
TI  - Flexural strength of autopolymerizing denture reline resins with microwave
      postpolymerization treatment.
AB  - STATEMENT OF PROBLEM: Microwave postpolymerization has been suggested as a method
      to improve the mechanical strength of repaired denture base materials. However,
      the effect of microwave heating on the flexural strength of the autopolymerizing
      denture reline resins has not been investigated. PURPOSE: This study analyzed the
      effect of microwave postpolymerization on the flexural strength of 4
      autopolymerizing reline resins (Duraliner II, Kooliner, Ufi Gel Hard, and Tokuso
      Rebase Fast) and 1 heat-polymerized resin (Lucitone 550). MATERIAL AND METHODS:
      For each material, 80 specimens (64 x 10 x 3.3 mm) were polymerized according to
      the manufacturer's instructions and divided into 10 groups (n = 8). Control group
      specimens remained as processed. Before testing, the specimens were subjected to
      postpolymerization in a microwave oven using different power (500, 550, or 650 W)
      and time (3, 4, or 5 minutes) settings. Load measurements (newtons) were made at
      a crosshead speed of 5 mm/min using a 3-point bending device with a span of 50
      mm. The flexural strength values were calculated in MPa. Data analyses included 3
      way and 2-way analysis of variance and the Tukey Honestly Significant Difference
      test (alpha = .05). RESULTS: The flexural strengths of resins Duraliner II and
      Kooliner were significantly increased (P = .0015 and P = .0046, respectively)
      with the application of microwave irradiation using different time/power
      combinations. The materials Lucitone 550, Tokuso Rebase Fast, and Ufi Gel Hard
      demonstrated no significant strength improvement compared to the corresponding
      control. Only after microwave postpolymerization irradiation for 3 minutes at 550
      W did Lucitone 550 show significantly higher flexural strength (P =.001) than
      Tokuso Rebase Fast and Ufi Gel Hard relining resins. CONCLUSION: Microwave
      postpolymerization irradiation can be an effective method for increasing the
      flexural strength of Duraliner II (at 650 W) and Kooliner (at 550 W and 650 W for
      5 minutes).

PMID- 15942621
TI  - Provisional restorations for occlusal inlays using an orthodontic ligature tie.

PMID- 15942622
TI  - A technique to mount final casts with compromised interarticulator space.

PMID- 15942623
TI  - A procedure for repairing a fixed implant-supported complete denture.

PMID- 15942624
TI  - Soybean products and reduction of breast cancer risk: a case-control study in
      Japan.
AB  - Components of the Japanese diet, which might contribute to the relatively low
      breast cancer incidence rates in Japan, have not been clarified in detail. Since
      soybean products are widely consumed in Japan, a case-control study taking
      account of the menopausal status was conducted using data from the hospital-based
      epidemiologic research program at Aichi Cancer Center (HERPACC). In total, 167
      breast cancer cases were included and 854 women confirmed as free of cancer were
      recruited as the control group. Odds ratios (OR) and 95% confidence intervals
      (95% CI) were determined by multiple logistic regression analysis. There were
      reductions in risk of breast cancer associated with high intake of soybean
      products among premenopausal women. Compared with women in the lowest tertile,
      the adjusted ORs for top tertile intake of tofu (soybean curd) was 0.49 (95% CI,
      0.25-0.95). A significant decrease in premenopausal breast cancer risk was also
      observed for increasing consumption of isoflavones (OR=0.44; 95% CI, 0.22-0.89
      for highest vs lowest tertile; P for trend=0.02). The present study found a
      statistically inverse association between tofu or isoflavone intake and risk of
      breast cancer in Japanese premenopausal women, while no statistically significant
      association was evident with the risk among postmenopausal women.

PMID- 15942625
TI  - Breast and other cancers in 1445 blood relatives of 75 Nordic patients with
      ataxia telangiectasia.
AB  - Epidemiological studies have consistently shown elevated rates of breast cancer
      among female blood relatives of patients with ataxia telangiectasia (AT), a rare
      autosomal recessive disease. A large proportion of the members of AT families are
      carriers of AT-causing gene mutations in ATM (Ataxia Telangiectasia Mutated), and
      it has been hypothesised that these otherwise healthy carriers are predisposed to
      breast cancer. This is an extended and enlarged follow-up study of cancer
      incidence in blood relatives of 75 patients with verified AT in 66 Nordic
      families. Blood relatives were identified through population registry linkages,
      and the occurrence of cancer was determined from cancer registry files in each
      country and compared with national incidence rates. The ATM mutation carrier
      probabilities of relatives were assigned from the combined information on
      location in family, consanguinity, if any, and supplementary carrier screening in
      some families. Among the 1445 blood relatives of AT patients, 225 cancers were
      observed, with 170.4 expected, yielding a standardised incidence ratio (SIR) of
      1.3 (95% confidence interval (CI), 1.1-1.4). Invasive breast cancer occurred in
      34 female relatives (SIR, 1.7; 95% CI, 1.2-2.4) and was diagnosed in 21 women
      before the age of 55 years (SIR, 2.9; 95% CI, 1.8-4.5), including seven mothers
      of probands (SIR, 8.1; 95% CI, 3.3-17). When the group of mothers was excluded,
      no clear relationship was observed between the allocated mutation carrier
      probability of each family member and the extent of breast cancer risk. We
      concluded that the increased risk for female breast cancer seen in 66 Nordic AT
      families appeared to be restricted to women under the age of 55 years and was due
      mainly to a very high risk in the group of mothers. The findings of breast cancer
      risk in mothers, but not other likely mutation carriers, in this and other
      studies raises questions about the hypothesis of a simple causal relationship
      with ATM heterozygosity.

PMID- 15942626
TI  - Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance
      modulator, valspodar.
AB  - Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin
      when administered in combination, resulting in doxorubicin dose reduction. In
      animal models, valspodar has minimal interaction with pegylated liposomal
      doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we
      designed a study to determine maximum tolerated dose, dose-limiting toxicity
      (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar
      combination therapy in patients with advanced malignancies. Patients received PEG
      LD 20-25 mg m(-2) intravenously over 1 h for cycle one. In subsequent 2-week
      cycles, valspodar was administered as 72 h continuous intravenous infusion with
      PEG-LD beginning at 8 mg m(-2) and escalated in an accelerated titration design
      to 25 mg m(-2). Pharmacokinetic data were collected with and without valspodar. A
      total of 14 patients completed at least two cycles of therapy. No DLTs were
      observed in six patients treated at the highest level of PEG-LD 25 mg m(-2). The
      most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar
      erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in
      patients with breast and ovarian carcinoma. The mean (range) total doxorubicin
      clearance decreased from 27 (10-73) ml h(-1) m(-2) in cycle 1 to 18 (3-37) ml h(
      1) m(-2) with the addition of valspodar in cycle 2 (P=0.009). Treatment with PEG
      LD 25 mg m(-2) in combination with valspodar results in a moderate prolongation
      of total doxorubicin clearance and half-life but did not increase the toxicity of
      this agent.

PMID- 15942627
TI  - Gefitinib is more effective in never-smokers with non-small-cell lung cancer:
      experience among Asian patients.
AB  - We retrospectively analysed the results of patients with advanced non-small-cell
      lung cancer treated with gefitinib to derive clinical factors predictive of
      response and a favourable survival outcome. Patients were treated with gefitinib
      250 mg per day and re-evaluated 4-8 weeks later with repeat CT scan and every 8
      weeks thereafter to assess response and the duration of response. Pathology
      review by a histopathologist was conducted, in particular to confirm a recently
      published result of bronchioloalveolar carcinoma histology or its components as
      predictive of response to gefitinib. Logistic regression and Cox regression
      analytical methods were applied to determine factors that could predict for
      response and improved overall survival. A total of 110 patients were treated. The
      overall response rate was 32% partial responses (PRs). Only never-smoking status
      was predictive of response in the logistic regression analysis, adjusted OR=6.1,
      95% CI=1.7, 21.5. The presence of a PR and good performance status were
      predictive of a favourable survival outcome from the Cox regression modelling.
      Responders had an adjusted HR of 3.0, 95% CI=1.5-5.8 compared to nonresponders,
      while patients with ECOG status 0-1 had an adjusted HR of 0.42, 95% CI=0.25-0.72,
      compared with patients with ECOG status 2-4. Bronchioloalveolar carcinoma or its
      components were distinctly absent on pathology review. In conclusions, Never
      smoking status is an important clinical predictor of a favourable response to
      gefitinib.

PMID- 15942628
TI  - Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses
      cell migration and tumorigenic potential.
AB  - The reduction or loss of plakoglobin expression in late-stage bladder cancer has
      been correlated with poor survival where upregulation of this catenin member by
      histone deacetylase inhibitors has been shown to accompany tumour suppression in
      an in vivo model. In this study, we directly addressed the question of the role
      of plakoglobin in bladder tumorigenesis following restoration, or knockdown of
      expression in bladder carcinoma cell lines. Restoration of plakoglobin expression
      resulted in a reduction in migration and suppression of tumorigenic potential in
      vivo. Immunocytochemistry revealed cytoplasmic and membranous localisation of
      plakoglobin in transfectants with < 1% of cells displaying detectable nuclear
      localisation of plakoglobin. siRNA knockdown experiments targeting plakoglobin,
      revealed enhanced migration in all cell lines in the presence and absence of E
      cadherin expression. In bladder cell lines expressing low levels of plakoglobin
      and desmoglein-2, elevated levels of desmoglein-2 were detected following
      restoration of plakoglobin expression in transfected cell lines. Analysis of wnt
      signalling revealed no activation event associated with plakoglobin expression in
      the bladder model. These results show that plakoglobin acts as a tumour
      suppressor gene in bladder carcinoma cells and the silencing of plakoglobin gene
      expression in late-stage bladder cancer is a primary event in tumour progression.

PMID- 15942629
TI  - Randomised phase II evaluation of irinotecan plus high-dose 5-fluorouracil and
      leucovorin (ILF) vs 5-fluorouracil, leucovorin, and etoposide (ELF) in untreated
      metastatic gastric cancer.
AB  - An open-label randomised comparison of efficacy and tolerability of irinotecan
      plus high-dose 5-fluorouracil (5-FU) and leucovorin (LV) (ILF) with etoposide
      plus 5-FU/LV (ELF) in patients with untreated metastatic or locally advanced
      gastric cancer. One cycle of ILF comprised six once-weekly infusions of
      irinotecan 80 mg m(-2), LV 500 mg m(-2), 24-h 5-FU 2000 mg m(-2), and ELF
      comprised three once-daily doses of etoposide 120 mg m(-2), LV 300 mg m(-2), 5-FU
      500 mg m(-2). In all, 56 patients received ILF and 58 ELF. Median age was 62
      years, Karnofsky performance 90%, and disease status was comparable for both
      arms. The objective clinical response rates after 14 weeks treatment (primary end
      point) were 30% for ILF and 17% for ELF (risk ratio (RR) 0.57, 95% confidence
      interval (CI) 0.29-1.13, P = 0.0766). Overall response rates over the entire
      treatment period for ILF and ELF were 43 and 24%, respectively (RR 0.56, 95% CI
      0.33-0.97; P = 0.0467). For ILF and ELF, respectively, median progression-free
      survival was 4.5 vs 2.3 months, time to treatment failure was 3.6 vs 2.2 months
      (P = 0.4542), and overall survival was 10.8 vs 8.3 months (P = 0.2818). Both
      regimens were well tolerated, the main grade 3/4 toxicities being diarrhoea (18%,
      ILF) and neutropenia (57%, ELF). The data from this randomised phase II study
      indicate that ILF provides a better response rate than ELF, and that ILF should
      be investigated further for the treatment of metastatic gastric cancer.

PMID- 15942630
TI  - Type distribution, viral load and integration status of high-risk human
      papillomaviruses in pre-stages of cervical cancer (CIN).
AB  - A series of 176 archival cervical intraepithelial neoplasia (CIN) was analysed
      for the presence, viral load and integration status of 'high-risk' types of human
      papillomavirus (HR-HPV). The samples were assayed using newly developed methods
      based on real-time PCR. Two methods for the extraction of DNA from the paraffin
      embedded biopsies were compared: a protocol based on the MagNA pure system
      (Roche) and a Qiagen spin column kit (Qiagen). It was possible to amplify 94%
      (166) of the samples. Of these, 36, 63 and 80% of the CIN I, II and III cases
      contained HR-HPV. HPV 16 was the most prevalent, and was found in 20, 28 and 46%
      of the CIN I, II and III cases, respectively. The second most frequent HR-HPV was
      type 33 group, and in CIN II it was as prevalent as HPV 16. The median number of
      copies of HR-HPV per cell was not significantly different in the CIN I, II and
      III cases, but there was a wide range of viral load values over several
      magnitudes, regardless of the grade of CIN. All samples were found to contain
      integrated forms of HPV 16, frequently mixed with an episomal form.

PMID- 15942631
TI  - Capecitabine plus docetaxel every 3 weeks in first- and second-line metastatic
      oesophageal cancer: final results of a phase II trial.
AB  - Capecitabine and docetaxel have single-agent activity in upper gastrointestinal
      tumours, and have together demonstrated preclinical synergy and a survival
      benefit in breast cancer, and high response rates in first-line metastatic
      gastric cancer. This trial assessed the efficacy, safety and feasibility of
      capecitabine in combination with docetaxel in patients with metastatic
      oesophageal cancer. In all, 24 patients with advanced disease (17 squamous cell
      carcinoma and seven adenocarcinoma) received oral capecitabine (1000 mg m(-2)
      twice daily on days 1-14) plus intravenous docetaxel (75 mg m(-2) on day 1) every
      3 weeks as first- (n = 16) or second-line (n = 8) therapy. Patients received a
      median of four cycles of treatment (range, 0-6). The median follow-up is 16.5
      months (range, 7.9-21.4 months). Intent-to-treat efficacy analysis showed an
      overall response rate of 46%. Of the 11 responders (one complete and 10 partial),
      nine of 16 (56%) received first-line and two of eight (25%) received second-line
      therapy. The median time to progression was 6.1 months (95% confidence interval
      (CI), 4.5-7.7 months). The median survival was 15.8 months (95% CI, 7.8-23.9
      months). Severe adverse events (grade 3/4) reported were: neutropenia (42%,
      including febrile neutropenia 8%), hand-foot syndrome (29%), diarrhoea (13%),
      sensory neuropathy (13%), anaemia (8%) and fatigue (8%). Capecitabine plus
      docetaxel has a manageable adverse event profile and very promising activity in
      metastatic oesophageal cancer, at least comparable to other doublet regimens.
      Therefore, the combination merits further investigation in this setting.

PMID- 15942632
TI  - Phase I trial of oral S-1 combined with gemcitabine in metastatic pancreatic
      cancer.
AB  - The objective of this study was to determine the maximum tolerated dose (MTD) and
      dose-limiting toxicities (DLTs) of S-1, an oral fluorouracil derivative, combined
      with gemcitabine, the current standard treatment for advanced pancreatic cancer
      (APC). The subjects were histopathologically proven APC patients with distant
      metastasis. S-1 was administered orally twice daily each day for 14 days and
      gemcitabine on days 8 and 15 of each cycle, and this was repeated every 21 days.
      Doses of each drug were planned as follows: level 1: 800/60, level 2a: 800/80,
      level 2b: 1000/60, level 3: 1000/80 (gemcitabine (mg m(-2))/S-1 (mg m(-2) day(
      1))). In all, 21 patients with APC were enrolled. The main grade 3-4 toxicities
      observed during first cycle were neutropenia (33%), anaemia (10%),
      thrombocytopenia (14%) and anorexia (10%). There were no DLT observed in level 1.
      Three of six patients in level 2a had DLT and this level was considered the MTD.
      In all, 12 patients in level 2b had no DLT and this level was selected as the
      recommended dose. Applicable responses were one complete response and nine
      partial responses (48%). As toxicities were well tolerated and antitumour
      activities seem to be promising, this combination can be recommended for further
      phase II studies with APC.

PMID- 15942633
TI  - The value of immunohistochemistry in sentinel lymph node histopathology in breast
      cancer.
AB  - The optimal protocol for the histopathological examination of sentinel lymph
      nodes (SLNs) in breast cancer has not been determined. The value of more detailed
      examination using immunohistochemistry (IHC) is controversial. A total of 476
      SLNs from 216 patients were reviewed. Sentinel lymph nodes were sectioned at
      three levels at 100 mum intervals and stained with haematoxylin and eosin (H&E).
      If the H&E sections showed no evidence of metastasis, then the three serial
      sections were stained with a murine monoclonal anti-cytokeratin antibody (CAM
      5.2). Metastatic deposits were classified as macrometastasis (> 2.0 mm),
      micrometastasis (0.2-2.0 mm) or isolated tumour cells (ITC, < 0.2 mm). Of the 216
      patients, 56 (26%) had metastasis as identified by H&E. Immunohistochemistry
      detected metastatic deposits in a further nine patients (4%), of whom four (2%)
      had micrometastasis and five (2%) had ITC only. Those cases with micrometastases
      were all, on review, visible on the H&E sections. Immunohistochemistry detects
      only a small proportion of metastasis in SLNs. All metastatic deposits identified
      by IHC were either micrometastasis or ITC. Until the prognostic significance of
      these deposits has been determined, IHC may be of limited value in the
      histopathological examination of SLNs.

PMID- 15942634
TI  - The role of bioreductive activation of doxorubicin in cytotoxic activity against
      leukaemia HL60-sensitive cell line and its multidrug-resistant sublines.
AB  - Clinical usefulness of doxorubicin (DOX) is limited by the occurrence of
      multidrug resistance (MDR) associated with the presence of membrane transporters
      (e.g. P-glycoprotein, MRP1) responsible for the active efflux of drugs out of
      resistant cells. Doxorubicin is a well-known bioreductive antitumour drug. Its
      ability to undergo a one-electron reduction by cellular oxidoreductases is
      related to the formation of an unstable semiquionone radical and followed by the
      production of reactive oxygen species. There is an increasing body of evidence
      that the activation of bioreductive drugs could result in the alkylation or
      crosslinking binding of DNA and lead to the significant increase in the cytotoxic
      activity against tumour cells. The aim of this study was to examine the role of
      reductive activation of DOX by the human liver NADPH cytochrome P450 reductase
      (CPR) in increasing its cytotoxic activity especially in regard to MDR tumour
      cells. It has been evidenced that, upon CPR catalysis, DOX underwent only the
      redox cycling (at low NADPH concentration) or a multistage chemical
      transformation (at high NADPH concentration). It was also found, using superoxide
      dismutase (SOD), that the first stage undergoing reductive activation according
      to the mechanism of the redox cycling had the key importance for the metabolic
      conversion of DOX. In the second part of this work, the ability of DOX to inhibit
      the growth of human promyelocytic-sensitive leukaemia HL60 cell line as well as
      its MDR sublines exhibiting two different phenotypes of MDR related to the
      overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX) was studied in
      the presence of exogenously added CPR. Our assays showed that the presence of CPR
      catalysing only the redox cycling of DOX had no effect in increasing its
      cytotoxicity against sensitive and MDR tumour cells. In contrast, an important
      increase in cytotoxic activity of DOX after its reductive conversion by CPR was
      observed against HL60 as well as HL60/VINC and HL60/DOX cells.

PMID- 15942635
TI  - Potential diagnostic and prognostic values of detecting promoter hypermethylation
      in the serum of patients with gastric cancer.
AB  - While there is no reliable serum biomarker for the diagnosis and monitoring of
      patients with gastric cancer, we tested the potential diagnostic and prognostic
      values of detecting methylation changes in the serum of gastric cancer patients.
      DNA was extracted from the pretherapeutic serum of 60 patients with confirmed
      gastric adenocarcinoma and 22 age-matched noncancer controls. Promoter
      hypermethylation in 10 tumour-related genes (APC, E-cadherin, GSTP1, hMLH1, MGMT,
      p15, p16, SOCS1, TIMP3 and TGF-beta RII) was determined by quantitative
      methylation-specific PCR (MethyLight). Preferential methylation in the serum DNA
      of gastric cancer patients was noted in APC (17%), E-cadherin (13%), hMLH1 (41%)
      and TIMP3 (17%) genes. Moreover, patients with stages III/IV diseases tended to
      have higher concentrations of methylated APC (P = 0.08), TIMP3 (P = 0.005) and
      hMLH1 (P = 0.03) in the serum. In all, 33 cancers (55%) had methylation detected
      in the serum in at least one of these four markers, while three normal subjects
      had methylation detected in the serum (specificity 86%). The combined use of APC
      and E-cadherin methylation markers identified a subgroup of cancer patients with
      worse prognosis (median survival 3.3 vs 16.1 months, P = 0.006). These results
      suggest that the detection of DNA methylation in the serum may carry both
      diagnostic and therapeutic values in gastric cancer patients.

PMID- 15942636
TI  - Expression of pendrin in benign and malignant human thyroid tissues.
AB  - The Pendred syndrome gene (PDS) encodes a transmembrane protein, pendrin, which
      is expressed in follicular thyroid cells and participates in the apical iodide
      transport. Pendrin expression has been studied in various thyroid neoplasms by
      means of immunohistochemistry (IHC), Western blot and RT-quantitative real-time
      PCR. The expression was related to the functional activity of the thyroid tissue.
      Follicular cells of normal, nodular goitre and Graves' disease tissues express
      pendrin at the apical pole of the thyrocytes. In follicular adenomas, pendrin was
      detected in cell membranes and cytoplasm simultaneously in 10 out of 15 cases.
      Pendrin protein was detected in 73.3 and 76.7% of the follicular (FTC) and
      papillary (PTC) thyroid carcinomas, respectively, where pendrin was solely
      localised inside the cytoplasm. An extensive intracellular immunostaining of
      pendrin was observed in six out of 11 (54.5%) of positive FTCs and 19 out of 23
      (82%) of PTCs. Focal reactivity was detected in one follicular- and three
      papillary carcinomas, whereas pendrin protein was absent in three of 15 FTC and
      four of 30 PTC; mRNA of pendrin was detected in 92.4% of thyroid tumours. The
      relative mRNA expression of pendrin was lower in cancers than in normal thyroid
      tissues (P<0.001). The pendrin protein level was found to parallel its mRNA
      expression, which was not, however, related to the tumour size and tumour stage.
      In conclusion, pendrin is expressed in the majority of differentiated thyroid
      tumours with high individual variability but its targeting to the apical cell
      membrane is affected.

PMID- 15942637
TI  - Hyaluronidase induces a transcapillary pressure gradient and improves the
      distribution and uptake of liposomal doxorubicin (Caelyx) in human osteosarcoma
      xenografts.
AB  - Liposomal drug delivery enhances the tumour selective localisation and may
      improve the uptake compared to free drug. However, the drug distribution within
      the tumour tissue may still be heterogeneous. Degradation of the extracellular
      matrix is assumed to improve the uptake and penetration of drugs. The effect of
      the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and
      microvascular pressure were measured in human osteosarcoma xenografts by the wick
      in-needle and micropipette technique, respectively. The tumour uptake and
      distribution of liposomal doxorubicin were studied on tumour sections by confocal
      laser scanning microscopy. The drugs were injected i.v. 1 h after the
      hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced
      interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum
      interstitial fluid pressure reduction of approximately 50% was found after
      injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of
      hyaluronidase induced any changes in the microvascular pressure. Thus,
      hyaluronidase induced a transcapillary pressure gradient, resulting in a four
      fold increase in the tumour uptake and improving the distribution of the
      liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by
      inducing a transcapillary pressure gradient, and administration of hyaluronidase
      adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome.

PMID- 15942638
TI  - The frequency of Trp64Arg polymorphism of the beta3-adrenergic receptor gene in
      healthy and obese Hungarian children and its association with cardiovascular risk
      factors.
AB  - OBJECTIVE: To estimate the frequency of Arg64 allele of the beta(3)-adrenergic
      receptor (3-BAR) gene in healthy (H) and obese (O) Hungarian children, and to
      look for possible associations between this polymorphism and some clinical and
      metabolic characteristics of obese children. PATIENTS/METHODS: In all, 147
      healthy (male: 68) and 295 obese (male: 168) children were examined. The average
      age of the children in the two groups was 12.4+/-1.7 vs 12.6+/-3.2, respectively.
      Exon 1 of 3-BAR was amplified by polymerase chain reaction and the fragments were
      digested with BstN1. In obese children, oral glucose tolerance test was carried
      out and blood pressure (BP) was checked. RESULTS: The frequency of Trp64Arg
      polymorphism in normal and obese Hungarian children was similar (H vs O:
      n=14/9.5% vs n=35/11.8%). Obese children carrying the Arg64 allele (n=35, male:
      23) were compared to randomly chosen, obese children without the Arg64 allele
      (n=35, male: 20). A significant difference was found between the body weight
      (81.2+/-23.2 vs 75.6+/-17.7 kg; mean+/-s.d.; P<0.01), body fat (38.8+/-3.9 vs
      36.5+/-2.3%; mean+/-s.d.; P<0.05), mean fasting insulin levels (31.4+/-16.7 vs
      16.9+/-7.6 microIU/ml; P<0.001) and mean systolic BP values (125.2+/-10.1 vs
      114.5+/-8.3 mmHg; P<0.001) of the two obese groups. CONCLUSIONS: The frequency of
      Trp64Arg polymorphism was similar in Hungary as compared to other European
      countries. Although the prevalence of this polymorphism was similar in H and O
      children, the presence of Arg64 allele seems to be associated with increased
      adiposity, elevated systolic BP and higher fasting insulin levels.

PMID- 15942639
TI  - Nutrition education for care staff and possible effects on nutritional status in
      residents of sheltered accommodation.
AB  - OBJECTIVE: We investigated the nutritional, cognitive and functional status in
      residents of two service-flat (SF) complexes and the effects of a nutrition
      education programme for care staff. DESIGN: Controlled nonrandomised study.
      SETTING: Two SF complexes, that is community-assisted accommodation. SUBJECTS: Of
      115 eligible SF residents, 80 subjects participated (age 83+/-7 y, 70% women).
      INTERVENTION: The nutritional status was assessed using body mass index (BMI,
      kg/m(2)), subjective global assessment (SGA), serum concentrations of albumin,
      insulin-like growth factor-I (IGF-I) and vitamin B(12). Cognitive and functional
      status were evaluated using the Mini Mental State Examination (MMSE, 0-30 points,
      <24 points indicates impaired cognition) and the Katz activities of daily living
      (ADL) index, respectively. Two assessments were made with a 5-month interval. At
      the start, a 12-h education programme was given to the staff at one of the SF
      complexes. RESULTS: At baseline, the means of BMI and the biochemical nutritional
      indices were normal, whereas one-third had BMI <22 kg/m(2) and one-fourth had
      lost > or =10% of previous weight. According to SGA, 30% demonstrated possible or
      serious malnutrition. The median MMSE was 23 points (19.5-26.5, 25-75th
      percentile). Nearly 70% were ADL-independent. At the 5-month follow-up there were
      no differences in the nutritional and cognitive status of the residents. The
      nutritional knowledge of the staff improved slightly (P<0.05) at both SF
      complexes (NS between groups). CONCLUSIONS: Around one-third of SF residents
      appeared to be at nutritional risk. Five months after a 12-h staff nutrition
      education programme, no objective changes were seen in the nutritional status of
      the SF residents.

PMID- 15942640
TI  - Nutritional status study of inpatients in hospitals of Galicia.
AB  - OBJECTIVE: To know the prevalence of malnutrition and to validate a nutritional
      screening protocol (SP) in patients hospitalised in Hospitals representative of
      inpatients admitted for acute illnesses in Galicia. DESIGN: Cross-sectional study
      of 376 randomised patients (189 female, 210 > or =65 y old) from 12 public
      hospitals admitted to hospital for acute medical, surgical or trauma illnesses.
      The patients elicited were evaluated by a simple SP, including variables relative
      to recent weight changes, serum albumin, lymphocytes, food ingestion and
      diagnosis at admission (Cardona's Protocol), and with a diagnostic protocol (DP,
      Subjective Global Assessment). Both SP and DP were performed by personnel trained
      in nutritional evaluation. Results of SP and DP were compared; principal factors
      related to malnutrition were also analysed; statistical significance was
      considered at P<0.05. RESULTS: From patients studied, according to DP 169/360
      (46.94%), patients presented malnutrition (134 B category and 35C category). SP
      rate was significantly related to severity of malnutrition detected by DP
      (P<0.001). The principal factors related to the presence of malnutrition were
      older age and degree of metabolic stress. CONCLUSIONS: In adult patients admitted
      for acute illnesses, the prevalence of protein-energy malnutrition is high. The
      risk was related to age and to metabolic stress. The risk of malnutrition in a
      hospital setting is evaluated appropriately by a simple screening procedure that
      may contribute to detecting and correcting malnutrition risk.

PMID- 15942641
TI  - Retrospective assessment of exposure to traffic air pollution using the ExTra
      index in the VESTA French epidemiological study.
AB  - This study applies a traffic exhaust air dispersion model (the ExTra index) to
      403 children enrolled in a French multicentric case-control study, the VESTA
      study (Five [V] Epidemiological Studies on Transport and Asthma). The ExTra index
      (previously validated by our team) was used to assess lifelong average traffic
      related air pollutant (TAP) concentrations (nitrogen oxides) children in the
      study were exposed to in front of their living places. ExTra index took into
      account traffic density, topographical parameters (building height, road and
      pavement width), weather conditions (wind direction and strength) and background
      pollution levels. Topographical and traffic data were collected, using a specific
      questionnaire for each home, school or nursery address, attended by children. The
      assessment of time-weighted NOx levels in front of the children's living places
      highlighted significant disparities: mean ExTra index values and share
      attributable to proximity traffic were, respectively, 70+/-42 and 14+/-22
      microg/m3 NOx equivalent NO2 for the 403 children in our study. Not only would
      this diversity not have been revealed using urban background pollution data
      provided by air quality networks, it would have resulted in 40% of the children
      being misclassified with regard to their TAP exposure by underestimating it in
      half of the cases and overestimating it in the other half. Such errors of
      classification, which are highly prejudicial in epidemiology, argue strongly for
      the use of an index such as the ExTra, which enables TAP exposure to be
      reconstructed within the framework of retrospective or prospective
      epidemiological studies.

PMID- 15942642
TI  - Human natural killer cells: a comprehensive review.
AB  - The senior author of this comprehensive review observed and reported in 1969 that
      his lymphocytes killed allogeneic tumor cells in vitro. Some of his research
      associates and technicians and other healthy individuals also yielded such killer
      lymphocytes. The team considered pre-immunization to cancer occurring in
      individuals after in-family or professional exposure to patients with cancer (in
      an era when the concept of viral etiology of cancer was receiving major support);
      or that lymphocytes can acquire through blastic transformation immune reactivity
      to allogeneic cells anew in vitro. The phenomenon was eventually referred to as
      'lymphocytes practicing Burnet's immunosurveillance.' Project site visitors of
      the USA NCI first viewed these observations as a matter of 'in vitro artifacts'
      being in opposition to strong tumor- specific cytotoxicity of tumor-bearing
      patients' lymphocytes recognized in the vast majority of other assays. After NCI
      funds were released for intramural studies on the phenomenon of non-specific
      cytotoxicity by lymphocytes, recipients (other than the senior author) of these
      NCI funds later characterized (1973-1975) the 'indiscriminately' cytotoxic
      lymphocyte populations as those of 'natural killer (NK) cells.' In this article,
      the original observations made in 1969-1971 are reviewed based on genuine
      material preserved by the senior author and are explained in view of recent
      discoveries that were not available at the time of the original observations. NK
      cells display a fascinating history arising first in urochordates during the
      cambrian explosion. At that level, NK cells protected their hosts from
      incompatible cell colony fusions and against intracellular, especially viral,
      pathogens. Since then, viruses evolved evasive maneuvers to escape NK cell attack
      on the infected cells. NK cells persisted after the evolution of adaptive
      immunity in cartilaginous fish fitting seamlessly into the new system. In
      mammals, NK cells assumed the role of chief arbitrators between the fetal
      trophoblast and maternal immune reactions to the semi-allograft fetus. Tumors
      induce in NK cells the same (inactivating; mediating Th2-type immunity) reactions
      the fetal trophoblast engenders in utero, but NK cells may overcome the host's
      tolerance to its tumor and kill tumor cells, especially when converted into
      lymphokine-activated killer (LAK) cells by molecular mediators of Th1-type
      immunity. The authors prepare and utilize LAK cells and IL-2 for adoptive
      immunotherapy of patients with metastatic melanoma and kidney carcinoma. A
      patient with malignant ascites due to ovarian carcinoma entered remission on LAK
      cell therapy. Just as dendritic cells, the major antigen presentors, may undergo
      malignant transformation, NK cells are also subject to transformation into FasL
      producer virulent lymphoma-leukemia cells. The senior author reported in 1970 a
      patient with 'lymphosarcoma cell leukemia' whose circulating lymphoma cells
      killed indiscriminately human sarcoma and carcinoma cells. The exemplary case
      history of another patient with NK cell lymphoma-leukemia treated by the authors
      is presented.

PMID- 15942643
TI  - Expression of epithelial cell adhesion molecule in carcinoma cells present in
      blood and primary and metastatic tumors.
AB  - The epithelial cell adhesion molecule (EpCAM) is involved in homophilic cell-cell
      adhesion in normal epithelia and is frequently overexpressed in primary and
      metastatic adenocarcinomas. It has been postulated that during detachment and
      dissemination of tumor cells, EpCAM may be down-regulated. Circulating tumor
      cells (CTC) may demonstrate this phenomenon as they have successfully escaped
      their local microenvironment and entered the circulation. EpCAM expression of CTC
      was compared to tumor cells in paraffin-embedded tissue arrays containing various
      benign diseases and carcinomas. EpCAM expression on CTC was determined by flow
      cytometry (FCM) and by immunohistochemistry (IHC) in paraffin-embedded tissue. To
      permit comparison of FCM results to those derived by IHC, EpCAM was quantified on
      cancer cell lines by FCM and then paraffin-embedded cell-blocks of these lines
      were used as staining guides for IHC analysis of tissue arrays. By IHC, 97%
      (384/397) of solid tissues analyzed had detectable EpCAM, with 72% of tissues
      showing antigen expression levels of > or =400,000 EpCAM molecules per cell. FCM
      analysis of CTC from 100 metastatic carcinoma patients with > or =2 CTC/90 microl
      blood showed EpCAM expression ranging from 9,900 to 246,000 (mean 49,700)
      antigens per cell. EpCAM expression was approximately 10-fold lower on CTC as
      compared to primary and metastatic tissues, suggesting that EpCAM expression is
      transient and dependent upon the local micro-environment. This supports the
      hypothesis that this adhesion molecule is down-regulated on carcinoma cells in
      the circulation.

PMID- 15942644
TI  - Identification of differentially expressed proteins in oral squamous cell
      carcinoma using a global proteomic approach.
AB  - A number of protein markers for oral cancer are still not applicable in large
      populations. Proteomic technologies provide excellent tools for rapid screening
      of a large number of potential biomarkers in malignant cells. To gain insight
      into the molecular mechanisms of carcinogenesis and to identify potential
      biomarkers for oral squamous cell carcinomas (OSCCs), we performed proteomic
      profiling between human normal oral keratinocytes (HNOKs) and OSCC-derived cell
      lines (HSC-2 and HSC-3) using fluorescent two-dimensional difference in-gel
      electrophoresis. Proteins with a > or =2-fold change in expression were
      considered significant. The spots of interest were digested and identified by
      matrix-assisted laser desorption/ionization time-of-flight peptide mass finger
      printing. Twenty-two proteins were identified as differentially expressed between
      the HNOKs and OSCC-derived cell lines. Of these, 9 spots were up-regulated and 13
      were down-regulated in OSCC-derived cell lines compared to the HNOKs. These spots
      included the cancer-related proteins; annexin A1, heat shock protein 27, lamin
      A/C, interleukin 1 receptor antagonist, serine proteinase inhibitor clade B5,
      stathmin 1, and superoxide dismutase 2. Our results are a first step toward
      identifying a protein profile of HNOKs and OSCC-derived cell lines. The
      identified proteins in this experiment may be used in future studies of
      carcinogenesis or as diagnostic markers and therapeutic targets for OSCC.

PMID- 15942645
TI  - Effects of p21cip1/waf1 overexpression on growth, apoptosis and differentiation
      in human colon carcinoma cells.
AB  - The cyclin-dependent kinase inhibitor p21cip1/waf1 negatively regulates the
      progression of cell cycle and the potential usefulness of p21cip1/waf1 gene is
      proposed in gene therapy. However, studies have demonstrated a protective role of
      p21cip1/waf1 against apoptosis and little is known about effects of ectopic
      expression of p21cip1/waf1 on differentiation of colon cancer cells. In the
      present study, we found diffuse p21cip1/waf1 expression in only a few clinical
      samples of colorectal cancer with wild-type p53 gene. To explore the role of
      p21cip1/waf1 in cell growth, apoptosis and differentiation, we constitutively
      overexpressed p21cip1/waf1 in HT29 colon carcinoma cells. Ectopic overexpression
      of p21cip1/waf1 was associated with inhibition of CDK2-associated kinase
      activity, indicating the functionality of the introduced p21cip1/waf1 gene.
      Overexpression of p21cip1/waf1 caused an appreciable growth inhibition in
      monolayer and soft agar cultures and it significantly reduced sodium butyrate-
      but not 5-fluorouracil-induced apoptosis. p21cip1/waf1 overexpressing cells
      exhibited marked decrease of intestinal differentiation when assayed with
      intestinal alkaline phosphatase. Our findings suggest that introduction of
      p21cip1/waf1 gene into colon cancer cells may be useful for inhibiting cell
      growth but caution should be taken regarding the increased resistance to certain
      apoptosis-inducing agents and dysregulation of endogenous p21cip1/waf1-mediated
      differentiation process.

PMID- 15942646
TI  - Adenoviral gene transduction of hepatocyte growth factor elicits inhibitory
      effects for hepatoma.
AB  - Hepatocyte growth factor (HGF) gene therapy may have potential for treating
      chronic hepatitis (CH) and liver cirrhosis (LC). However, the lack of an HGF gene
      therapy study on hepatomas that are often associated with CH or LC, together with
      the stimulatory effects of HGF on many types of cancer, may hamper its
      application. This study explored the effects of adenoviral HGF gene transduction
      and their mechanisms on two types of hepatoma cells (hepatoblastoma and
      hepatocellular carcinoma) in in vitro experiments. Both types of hepatomas were
      revealed to have higher adenoviral gene transduction efficiencies and more
      efficient expressions of the HGF transgene, which successfully activated the HGF
      receptor/c-Met in an autocrine fashion, than those of other types of cancer.
      Notably, not only HGF, but also adenoviral infection, inhibited DNA synthesis,
      whereas only HGF but not adenoviral infection exerted a potent apoptotic effect.
      Moreover, adenoviral HGF gene transduction additively exerted inhibitory effects
      on cisplatin-treated hepatomas. In conclusion, inhibitory and apoptotic effects
      of adenoviral HGF gene transduction in hepatomas in contrast to potent mitogenic
      and antiapoptotic effects of HGF for hepatocytes are not only of biological
      interest, but also pose clinical benefits for adenoviral HGF gene therapy for CH
      and LC.

PMID- 15942647
TI  - Differentially expressed genes throughout the cellular immortalization processes
      are quite different between normal human fibroblasts and endothelial cells.
AB  - It is widely accepted that activation of telomerase and maintenance of telomeres
      play central roles in cellular immortalization for most cancer cells. However,
      they seem to be insufficient for normal human cells. To elucidate critically
      responsible genes for telomerase mediated cellular immortalization in non
      cancerous cells, we explored the genes that are differentially expressed
      throughout the immortalization process of normal human cells using cDNA
      microarrays with novel normalization procedures. We found that the number of
      genes, differentially expressed during cellular immortalization after ectopic
      expression of telomerase, dramatically increased in a later phase, especially in
      fibroblasts. We identified 18 and 20 genes/ESTs dysregulated throughout the
      cellular immortalization processes in fibroblasts and endothelial cells,
      respectively, but none of them overlapped. Only BGN and COL5A2 were commonly
      downregulated, except for at early phase in fibroblasts, and a few genes showed
      controversial expression changes, with regard to previous reports in cancer
      cells. These findings indicate that normal somatic cells would require cell-type
      specific events in addition to telomerase activation, and a rare population that
      eventually experience such events would acquire immortality. The key molecules
      that distinguish the immortalization mechanisms in cancerous and non-cancerous
      cells may become crucial targets for anticancer therapy and regenerative therapy.

PMID- 15942648
TI  - Expression and functional analyses of mHAUSP regulating apoptosis of cervical
      adenocarcinoma cells.
AB  - p53 tumor suppressor protein is stabilized by the herpes-virus-associated
      ubiquitin-specific protease (HAUSP), a deubiquitinating enzyme. We previously
      isolated a mouse orthologue of HAUSP, mHAUSP, encoding 1103 amino acids with a
      molecular weight of approximately 135 kDa containing highly conserved Cys, Asp
      (I), His, and Asn/Asp (II) domains. In this study, we investigated the temporal
      and spatial expression of mHAUSP during the early mouse embryonic development.
      Northern blot analysis revealed that the expression of mHAUSP was detected
      throughout the process of embryonic development with the maximal expression
      between E10.5 and E13.5. In situ hybridization study showed the global expression
      of mHAUSP in various organs of embryos, including mesencephalon, spinal cord,
      lung and genital eminence. In addition, we carried out biochemical analysis for 6
      conserved amino acids (Cys224, Gln231, Asp296, His457, His465, and Asp482) in Cys
      box, QQD box, and His box in order to investigate their structural and functional
      roles of these amino acid residues. The conserved Gln231 was not essential for
      the catalytic activity of mHAUSP. However, other conserved amino acids were
      required for deubiquitinating enzyme activity of mHAUSP. Moreover, we observed
      that the overexpression of mHAUSP induces cell death in HeLa cells.

PMID- 15942649
TI  - Methylation discriminators in NSCLC identified by a microarray based approach.
AB  - Aberrant DNA methylation is a frequent phenomenon in non-small cell lung cancers.
      We have used a microarray approach to assess the methylation status of 245 CpG
      positions in 59 candidate genes in 26 squamous cell carcinomas, and 22
      adenocarcinomas as well as 26 normal adjacent lung tissue samples from smokers to
      identify genes that show a distinct methylation status difference between the two
      different tumour type tissues and normal adjacent tissue. Tumour tissue samples
      were grouped together and compared to the normal tissue sample group. A
      multivariate test was performed, taking into account all CpG positions that were
      analyzed for a particular gene, to calculate p-values for each gene based on the
      observed methylation difference between the two groups, p-values obtained were
      corrected for multiple testing. The highest degree of differential DNA
      methylation in squamous cell carcinoma compared to normal was observed in ARHI,
      MGMT, GP1bbeta, RARbeta and TMEFF2 genes, while TMEFF2, MGMT and CDKNIC genes
      differentiated between adenocarcinomas and normal tissue. It is of note that some
      of the genes for which differential methylation status was observed, have not
      been previously described in lung cancer. Our results provide compelling evidence
      that different histological types of lung cancer may be distinguished from normal
      tissue based on methylation profiles of specific genes.

PMID- 15942650
TI  - A mouse model for developing treatment for secondary liver tumors.
AB  - Metastatic colorectal cancer is the second most common cause of cancer mortality.
      The liver is a common site of metastasis and only a minority of patients with
      liver metastases are candidates for potentially curative surgical resection. The
      treatment of patients with unresectable liver tumors is a major clinical problem
      and survival remains low. Many animal models of hepatic metastasis do not result
      in disease which resembles the advanced cancer setting. The purpose of this study
      was to establish a murine model for use in the evaluation of therapy for
      secondary liver cancer. Human colon cancer cells were injected directly into the
      portal vein of nude mice. Magnetic resonance imaging (MRI), performed weekly, was
      used to follow the time-course and characteristics of tumor growth. As expected,
      tumor size increased proportionately with time, following inoculation, and the
      MRI images correlated well with gross pathology findings at necropsy with respect
      to both tumor size and location. The tumors retained important morphology and
      biological characteristics of human colon cancer. Mice bearing liver metastasis
      were treated with irinotecan or drug vehicle. MRI evaluation pre/post-therapy
      gave an objective measure of therapeutic response. Irinotecan therapy was able to
      double the survival (median 76-93 days) compared to vehicle alone (median 43-46
      days). This murine model is reproducible, rapid, inexpensive and has an excellent
      success rate for the development of liver metastasis (100%). When used in
      conjunction with small animal MRI, this model allows the efficient evaluation of
      the therapeutics of liver metastasis without the use of repeated laparotomy or
      splenectomy and without requiring large numbers of animals undergoing terminal
      experiments.

PMID- 15942651
TI  - Comparison of immunocytochemistry, real-time quantitative RT-PCR and flow
      cytometry for detection of minimal residual disease in neuroblastoma.
AB  - A quantitative and precise measure of treatment response is warranted in
      neuroblastoma patients. We compared three quantitative methods often used for
      detection of minimal residual disease in such patients. Specificity, sensitivity
      and concordance of immunocytochemistry, real-time quantitative reverse
      transcription polymerase chain reaction (RT-PCR) and flow cytometry were compared
      using experimental cell suspensions (n = 8) and clinical samples (n = 126).
      Neuroblastoma cells were identified by immunocytochemistry and flow cytometry
      using anti-GD2 (14.G2a) and anti-NCAM (5.1H11) antibodies, whereas tyrosine
      hydroxylase mRNA was the molecular target for quantitative RT-PCR. The
      sensitivity using flow cytometry was 1-2 logs less than using immunocytochemistry
      or quantitative RT-PCR. All control samples (n = 35) tested negative by
      immunocytochemistry, whereas 2/34 (6%) and 1/14 (7%) were false positive by
      quantitative RT-PCR and flow cytometry respectively. Concordant results were
      obtained in 85% of patient samples (n = 116) analyzed in parallel by quantitative
      RT-PCR and immunocytochemistry, whereas 71% of samples analyzed by flow cytometry
      and immunocytochemistry were concordant (n = 35). The correlation between tumor
      cell levels analyzed by quantitative RT-PCR and immunocytochemistry was high (r =
      0.78, p < 0.001). Quantitative RT-PCR and immunocytochemistry both reliably
      detected very low levels of neuroblastoma cells in clinical samples. The
      agreement and correlation between these methods were high. In comparison, flow
      cytometry was less sensitive.

PMID- 15942652
TI  - Expression of transcription factor Yin Yang 1 in prostate cancer.
AB  - The transcription repressor Yin Yang 1 (YY1) is expressed in several human cancer
      cell lines and its expression correlates with resistance to immune-mediated
      apoptosis. This study used tissue microarrays to investigate the expression and
      localization of YY1 in 1364 representative tissue samples from 246 hormone naive
      prostate cancer patients who underwent radical prostatectomy. Staining intensity
      and frequency measures for both YY1 nuclear and cytoplasmic expression were
      higher in neoplastic tissues and in PIN samples compared to matched benign cells
      (p < 0.0001 for all comparisons). Expression of YY1 is predominantly elevated in
      early malignancy (PIN), as well as in tumors of intermediate to high morphologic
      grade (Gleason's grade 3-5). Using multivariate Cox proportional hazards
      analysis, we observed that low nuclear YY1 staining is an independent predictor
      of a shorter time to recurrence (p = 0.012). Based on these results, we
      hypothesize that YY1 may play a role in prostate cancer development; however,
      decreased YY1 may give metastatic cells a survival advantage. These results may
      also implicate YY1 as a useful diagnostic and prognostic marker.

PMID- 15942653
TI  - Utilizing a GnRH-based chimeric protein for the detection of adenocarcinoma.
AB  - Since early diagnosis of many types of cancer greatly improves the chances for
      successful treatment, high-quality methods for cancer detection are necessary.
      Our laboratory develops chimeric proteins for targeted therapy, such as
      gonadotropin releasing hormone (GnRH)-based chimeric proteins for the targeted
      therapy of adenocarcinomas in humans. For chimeric proteins to cause specific
      cell death, they must first recognize specific receptors/binding sites expressed
      on the surface of target cells. Thus, we examined whether we could exploit these
      binding sites not only as targets for the killing of specific cells but also as a
      diagnostic marker for identifying adenocarcinomas, using the same chimeric
      proteins. In this report, we show that one such GnRH-based chimeric protein, GnRH
      Caspase3, can indeed serve as a diagnostic tool. GnRH-Caspase3 was able to
      specifically bind adenocarcinoma cells, as measured by FACS analysis and
      demonstrated with the aid of confocal microscopy and specific antibodies.
      Moreover, we found a correlation between cell sensitivity to treatment and the
      binding level of the chimeric protein to the cells. Hence, we suggest that in
      addition to their therapeutic potential, GnRH-based chimeric proteins can be used
      as a diagnostic tool for the detection of adenocarcinomas.

PMID- 15942654
TI  - Involvement of proteolytic activation of PKCdelta in cisplatin-induced apoptosis
      in human small cell lung cancer H69 cells.
AB  - Proteolytic activation of protein kinase C delta (PKCdelta) has been associated
      with apoptosis induced by the DNA damaging agent cisplatin. In cells undergoing
      apoptosis, caspase-3 cleaves PKCdelta at the site DMQD downward arrowN to
      generate a 40-kDa catalytic fragment. We have previously shown that the PKC
      signal transduction pathway regulates sensitivity of human small cell lung cancer
      H69 cells to cisplatin. In the present study, we have investigated if proteolytic
      activation of PKCdelta is essential for cisplatin-induced apoptosis in H69 cells.
      The caspase cleavage-resistant mutant PKCdelta (DMQA) was generated by mutating
      the aspartate residue at the site of proteolysis DMQD downward arrowN to alanine
      (D330A), and the wild-type and mutant PKCdelta were introduced into H69 cells.
      Cisplatin induced a substantial increase in PKCdelta catalytic fragment in H69
      cells overexpressing PKCdelta (H69/delta, and the level of PKCdelta catalytic
      fragment in H69 cells expressing DMQA mutant (H69/DMQA) was equivalent to that in
      H69 cells. However, the cleavage of poly(ADP-ribose) polymerase (PARP), another
      substrate for caspase-3, was similar in cells overexpressing wild-type PKCdelta
      and DMQA mutant PKCdelta. The ability of cisplatin to induce mitochondrial
      depolarization and cell death was also equivalent among the cell lines tested.
      These results suggest that the proteolytic fragment of PKCdelta does not play a
      critical role in the induction of apoptosis in H69 cells.

PMID- 15942655
TI  - Theophylline stimulates cAMP-mediated signaling associated with growth regulation
      in human cells from pulmonary adenocarcinoma and small airway epithelia.
AB  - The methylxanthine theophylline is contained in tea and in numerous asthma and
      cold medications. Theophylline inhibits the enzyme phosphodiesterase, thereby
      preventing the intracellular break-down of cAMP. The resulting increase in
      intracellular cAMP reduces smooth muscle tone, thus dilating the airways.
      Epidemiologic studies on preventive effects of tea on the development of lung
      cancer have yielded mixed results, with some studies demonstrating a reduction in
      lung cancer risk whereas others showed evidence for cancer promotion. On the
      other hand, preclinical studies in mouse models of lung cancer or in vitro
      systems have consistently demonstrated strong cancer preventive effects of tea
      and of polyphenols contained in tea. Investigations conducted in our laboratory
      have recently shown that cell lines derived from human pulmonary adenocarcinomas
      of Clara cell lineage (PACC) and experimentally induced PACCs in a hamster model
      are under beta-adrenergic growth control. beta-adrenergic agonists as well as
      forskolin, which activates cAMP, had strong growth-promoting effects on human
      PACC cells and on the hamster PACCs. The current project therefore tests the
      hypothesis that theophylline activates growth-stimulating signaling in human PACC
      cells and their normal cells of origin, small airway epithelial cells (SAEC).
      Using assays for the assessment of intracellular cAMP, activated PKA,
      phosphorylated CREB, ERK1/2 and cell numbers, our data provide evidence for a
      significant stimulation of cell proliferation in both cell systems via activation
      of these signaling components.

PMID- 15942656
TI  - Physical status of HPV types 16 and 18 in topographically different areas of
      genital tumours and in paired tumour-free mucosa.
AB  - HPV16 and HPV18 integration into host cell DNA contributes to malignant
      transformation. Viral physical status was compared among samples from different
      tumour areas, and from tumour and paired non-lesional adjacent epithelium, in
      order to evaluate the levels of HPV integration that could account for local
      recurrences. Fifty-nine surgical biopsies were collected from 24 women with HPV16
      and/or HPV18-associated genital tumours, including 3 preinvasive and 21 invasive
      lesions. HPV integration was analysed by type-specific and multiplex PCRs for E6,
      E1 and E2 sequences. Nine tumours contained HPV16, 1 HPV18 and 14 both viruses.
      Intra-tumour heterogeneity occurred in 3 of the 10 tumours with multiple sampling
      (30%), including different HPV16 physical forms between core and periphery in 2
      cases, and different type of HPV infection in 1 case. Almost all tumours
      contained integrated forms of either HPV16 and/or HPV18. Analysis of the 15
      tumour-free tissues displayed 11 HPV-positive (73%) and 4 HPV-negative tissues.
      HPV16 was pure integrated in 1 case, mixed in 1 and episomal in 8, whereas HPV18
      was integrated in all 6 positive tissues (100%). When compared to the
      corresponding tumour, the positive control mucosa contained the same HPV type and
      the same physical status as the tumour in 6 cases, whereas 5 samples contained
      different HPV16 physical forms, episomal DNA being more frequent than in the
      lesion. These data showing the presence of high-risk HPV integrated forms in
      normal mucosa, especially in HPV18-positive cases, indicate that the research of
      viral integration in the adjacent tumour tissues may be a valuable tool in
      assessing risk factors for local recurrences.

PMID- 15942657
TI  - Inhibition of experimental U-118MG glioblastoma by targeted cytotoxic analogs of
      bombesin and somatostatin is associated with a suppression of angiogenic and
      antiapoptotic mechanisms.
AB  - Human gliomas express receptors for bombesin and somatostatin that can be used
      for targeted chemotherapy. In the present study, the efficacy and the mechanism
      of action of cytotoxic bombesin analog AN-215, and cytotoxic somatostatin analog
      AN-238 were investigated in U-118MG human glioblastomas xenografted into nude
      mice. The expression of vascular endothelial growth factor (VEGF) and the
      apoptotic markers Bcl-2 and Bax was analyzed by Western blotting. The toxicity
      was evaluated by measuring leukocyte levels and body weights. Treatment with AN
      215 or AN-238 reduced tumor growth by approximately 50%, and diminished the
      levels of VEGF by 45 and 75%, respectively. The relative ratio of Bcl-2 to Bax
      proteins was decreased by approximately 90%, indicating a net apoptotic gain and
      efficacy of treatment. Specific receptors for bombesin and somatostatin were
      found in U-118MG tumors. Our results suggest that targeted cytotoxic analogs, AN
      215 and AN-238, could be useful for the treatment of human glioblastomas.

PMID- 15942658
TI  - Development of a new hybrid gel phantom using carrageenan and gellan gum for
      visualizing three-dimensional temperature distribution during hyperthermia and
      radiofrequency ablation.
AB  - We developed a new hybrid gel phantom using carrageenan and gellan gum for the
      purpose of visualizing three-dimensional temperature distribution. The phantom,
      which contains carrageenan, gellan gum, non-ionic surface active agent, potassium
      chloride, n-butanol, sodium azide, and water, shows good transparency at room
      temperature, and has the advantage that the heated region becomes white and
      opaque due to segregation of the surface active agent. Carrageenan and gellan gum
      were added to improve the transparency and fragility of the hybrid gel. Potassium
      chloride was used to adjust the electrical conductivity of the gel to a range of
      5-130 MHz, so that it would be equivalent to that of muscle tissue for each
      frequency used by electromagnetic heating devices. N-butanol was used to adjust
      the clouding temperature to a range between 45 and 55 degrees C. In the present
      study we clarified the important properties of the new phantom, and developed
      formulae for easy determination of the amounts of ingredients necessary for the
      desired clouding temperature and electric conductivity. The characteristics of
      this phantom are: a) a solid form to avoid convection by heat conduction; b)
      sufficient strength without fragility to form a torso without the use of a
      reinforcing agent; c) high transparency at room temperature and visualization of
      the heating area as a white turbidity; d) time-lapse and accurate visualization
      of the changing temperature area without thermal hysteresis; e) electrical
      properties similar to those of human tissues; f) ease of production; and g) low
      cost and good safety. This phantom might assist oncologists in their routine
      checking and study of the performance of electromagnetic heating devices for
      hyperthermia and radiofrequency ablation.

PMID- 15942659
TI  - A polymorphism at codon 133 of the tumor suppressor RASSF1A is associated with
      tumorous alteration of the breast.
AB  - The tumor suppressor gene RASSF1A is inactivated or mutated in different tumor
      entities including breast cancer. The frequency of the genomic variants of
      RASSF1A in patients with breast tumors has not been evaluated. We studied the
      association between ten nucleotide polymorphisms of RASSF1A and the risk of
      breast cancer in 178 cases with tumorous alterations of mammary tissue (including
      141 carcinomas and 37 fibroadenomas) and 70 controls by SSCP and sequencing.
      Polymorphisms of RASSF1A were found at codon 28 and codon 133. The distribution
      of polymorphisms at codon 28 showed no significant difference between the patient
      groups: 5 of 178 (2.8%) in patients with tumorous alterations and 2 of 70 (2.9%)
      in control patients. However, the Gright curved arrow T polymorphism (GCTright
      curved arrow TCT; Alaright curved arrow Ser) at codon 133, which alters the
      microtubule association and stabilization domain of RASSF1A, exhibited a
      different genotype distribution: 29 out of 141 (20.6%) patients with breast
      carcinoma and 9 out of 37 (24.3%) patients with fibroadenoma harbored mutant T
      alleles. However, only in 2 out of 70 (2.9%) controls, the mutant T-allele was
      detected and therefore the frequency was significantly diminished compared to
      tumorous alterations (Fisher's exact test: carcinomas vs. controls, p = 0.0003;
      fibroadenoma vs. controls, p = 0.001). From five probands with homozygous TT
      genotype at codon 133, three were diagnosed with carcinomas and two with
      fibroadenomas. Our data indicate that the mutant T-allele of RASSF1A at codon 133
      is correlated with an increased number of breast tumors.

PMID- 15942660
TI  - Enhancement of the effect of 5-aminolevulinic acid-based photodynamic therapy by
      simultaneous hyperthermia.
AB  - In the present study, we have investigated a combination of photodynamic therapy
      (PDT) using 5-aminolevulinic acid (ALA) and simultaneous hyperthermia (HT) on
      osteosarcoma (HOSM-1) cells, squamous cell carcinoma (KB) cells and fibroblasts
      (HF), including an assessment of the differences in the sensitivity of these
      cells to such treatment in vitro. The intracellular accumulation of
      protoporphyrin IX (PPIX) formed by metabolism of ALA in mitochondria and the
      influence of the treatment on the mitochondrial membrane potential were evaluated
      using flow cytometry. The antitumor effects of HT, PDT using ALA (ALA-PDT) and
      ALA-PDT combined with HT (PDT+HT) were determined by an MTT assay. Western blot
      analysis of the expression of heat shock protein 60 (Hsp60) and Hsp70 was
      performed to evaluate the mitochondrial stress caused by each treatment. The
      intracellular PPIX accumulation in HOSM-1 cells was about 2-fold higher than that
      in KB cells. An antitumor effect of ALA-PDT and PDT+HT was obtained in each cell
      line, and indicated a synergistic interaction of the combination therapy in tumor
      cells. A marked degree of depolarization of the mitochondrial membrane was
      observed in both tumor cell lines, and there was no marked difference in the
      degree of depolarization between the cell lines. Marked expression of Hsp60 was
      observed in HOSM-1 cells treated with PDT+ HT and ALA-PDT, but not in KB cells.
      Slightly increased expression of Hsp70 was observed for all treatments in both
      tumor cell lines. These results suggest that the antitumor effect of ALA-PDT
      therapy against malignant tumor cells is enhanced by simultaneous HT.
      Furthermore, the differences in sensitivity to these therapies between the two
      cell types may have occurred because PPIX was not effectively utilized in HOSM-1
      cells, compared to its utilization in KB cells.

PMID- 15942661
TI  - HIV-1 TAT protein transduction domain mediates enhancement of enzyme prodrug
      cancer gene therapy in vitro: a study with TAT-TK-GFP triple fusion construct.
AB  - Protein transduction domain (PTD) from HIV-1 TAT protein has been reported to
      translocate across the mammalian cell membrane, also as a part of fusion
      proteins. However, the true nature of TAT-mediated intercellular spreading is
      still under debate because it has been claimed to be a fixation artifact. To
      study the spreading of TAT fusion proteins and their potency to enhance thymidine
      kinase/ ganciclovir (HSV-TK/GCV) cancer gene therapy, we constructed a novel
      triple fusion protein containing TAT PTD, HSV-TK and green fluorescent protein
      (TAT-TK-GFP). This fusion protein has three functional domains in the same
      polypeptide, allowing reliable determination of the relationship between
      transduction rate and cell killing efficiency. TAT-TK-GFP was cloned into a
      lentivirus vector and used for analyses of TAT-mediated protein translocation and
      enhancement of HSV-TK/GCV cytotoxicity. The triple fusion protein was expressed
      correctly in vitro, but cell-to-cell translocation was not observed in rat glioma
      cells (BT4C). However, TAT-TK-GFP made BT4C and SKOV3.ip1 (human ovarian
      carcinoma) cells significantly more sensitive to ganciclovir than TK-GFP, whereas
      the effect in PC-3 human prostate carcinoma cells was more subtle. It was also
      observed that growth in lower serum concentration (2.5-5%) abolished the
      enhancement in BT4C cells, suggesting that high proliferation rate is one of the
      factors that contribute to TAT PTD-mediated enhancement of cytotoxicity. In
      summary, our results indicate that TAT PTD fusion proteins do not translocate
      intercellularly at detectable levels, but enhancement of the HSV-TK/GCV
      cytotoxicity can be detected in rat and human tumor cell lines in vitro.

PMID- 15942662
TI  - Regulatory roles of cell surface sialylation in susceptibility to
      sphingomyelinase in human diffuse large B cell lymphoma.
AB  - Sphingolipid metabolites are important regulators of cell growth and apoptosis.
      To clarify the biological roles of cell surface sialylation in the effects of
      sphingomyelinase (SM) treatment on cell viability, the human diffuse large B cell
      lymphoma cell line, HBL-2 with or without treatment with Vibrio cholerae
      neuraminidase, was incubated with exogenous bacterial SM which is a key enzyme of
      ceramide production from sphingolipids in cell membranes. SM treatment enhanced
      viability of HBL-2 cells compared to non-treatment after 6 h of incubation. On
      the other hand, viability of HBL-2 cells was decreased by SM treatment with
      neuraminidase pre-treatment after 6 and 24 h of incubation, and ceramide
      production on cell surfaces of SM treated cells was enhanced by neuraminidase
      treatment as shown by flow cytometric analysis. Furthermore, treatment with D
      threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor which
      specifically reduces the activity of UDP-glucose:ceramide glucosyltransferase in
      combination with SM treatment, causes the viability of HBL-2 cells to be
      decreased more with neuraminidase pre-treatment than without it. Exogenous C6
      ceramide induced HBL-2 cell death, and there was no difference in the effects of
      C6-ceramide after 6 h of incubation between treatment and non-treatment with
      neuraminidase. Together these data suggest that alteration in susceptibility of
      HBL-2 cells to SM by neuraminidase treatment may precede the process of ceramide
      production, and that cell death through the activation of SM, which induces
      ceramide production, is regulated by cell surface sialylation in DLBCL.

PMID- 15942663
TI  - GSK-3beta reactivation with LY294002 sensitizes hepatoma cells to chemotherapy
      induced apoptosis.
AB  - Constitutive activation of phosphatidylinositol 3-kinase (PI3K) confers
      resistance to apoptotic stimuli induced by chemotherapeutic agents in a variety
      of cancer cells. Therefore, the comprehension of mechanisms whereby PI3K
      downregulation interferes with chemotherapy is of major clinical interest for the
      elaboration of combined anticancer treatment modalities. Here, we examined the
      molecular mechanisms whereby the PI3K inhibitor LY294002 sensitized p53- and Fas
      deficient hepatoma cells to etoposide and camptothecin. LY294002 increased Hep3B
      cell susceptibility to chemotherapy-induced apoptosis by enhancing the expression
      of DR4 and DR5 and the activation of caspase-8 and -3. Moreover, LY294002
      mediated sensitization to chemotherapy involved mitochondrial Bax translocation
      and cytosolic cytochrome c accumulation. In Hep3B cells, LY294002 led to the
      reactivation of glycogen synthase kinase-3beta (GSK-3beta) by promoting its
      dephosphorylation on the serine 9 residue independently from Akt inhibition. The
      transient transfection of a constitutively active and non-phosphorylable S9AGSK
      3beta mutant sensitized cells to etoposide cytotoxic effects while cell treatment
      with the small GSK-3beta inhibitor SB-415286 repressed the sensitizing effect of
      LY294002 on chemotherapy-induced apoptosis and caspase-8 activation. Altogether,
      our results show that LY294002 sensitizes hepatoma cells to chemotherapy-induced
      apoptosis via death receptor and mitochondria signalling pathways and that GSK
      3beta reactivation is involved in this process. Therefore, PI3K-mediated GSK
      3beta inhibition could be a mechanism by which cancer cells escape from
      chemotherapy-induced apoptosis.

PMID- 15942664
TI  - The urokinase-type plasminogen activator, its receptor and u-PA inhibitor type-1
      affect in vitro growth and invasion of Kaposi's sarcoma and capillary endothelial
      cells: role of HIV-Tat protein.
AB  - The aggressive and malignant nature of AIDS-associated Kaposi's sarcoma (KS)
      lesions have largely been ascribed to Tat, the HIV-1 transactivator protein.
      Among other activities, HIV-Tat induces the migration and invasion of KS and
      endothelial cells. Since cell invasion is strictly correlated to the activity of
      lytic enzymes, we elucidated the role of the cell-associated plasminogen
      activation system in Tat-dependent and in constitutive invasion and proliferation
      of KS and of microvascular endothelial cells (MVEC). We demonstrate that KS cells
      and MVEC express the u-PA receptor (u-PAR) and release plasminogen activators and
      plasminogen activator inhibitor type-1 (PAI-1). The urokinase-type plasminogen
      activator (u-PA) is chemotactic, chemoinvasive and mitogenic for KS cells and for
      MVEC. Conditioned medium from KS cells induced invasion and proliferation of MVEC
      through the u-PA/u-PAR system. Tat is motogenic and mitogenic on KS cells and
      MVEC, and stimulates morphogenesis of MVEC. These activities were inhibited
      following antagonization of u-PA and u-PAR, which also reduced constitutive
      proliferation and invasion of KS cells and MVEC. These data indicate that the u
      PA/u-PAR/PAI-1 system is involved in KS-induced endothelial cell invasion,
      proliferation, and differentiation. Further, exogenous Tat protein could up
      regulate the fibrinolytic system, increasing its influence on KS and endothelial
      cell proliferation and migration, potentially promoting KS progression. These
      observations suggest the potential for application of u-PA/u-PAR system
      inhibitors for control of AIDS-associated KS, that has a high risk of recurrence
      with highly active antiretroviral therapy failure, and of other KS forms.

PMID- 15942665
TI  - Incorporating the survivin promoter in an infectivity enhanced CRAd-analysis of
      oncolysis and anti-tumor effects in vitro and in vivo.
AB  - Conditionally replicating adenoviruses (CRAds) represent a promising new modality
      for the treatment of cancer. A key contribution in this regard was the
      introduction of tumor-selective viral replication for amplification of the
      initial inoculum. Specifically, following cellular infection, the virus
      replicates selectively in the infected tumor cells and kills the cells by
      cytolysis. Next, the progeny virions infect surrounding target cells, replicate
      and eradicate the infected tumor cells, leaving normal cells unaffected. However,
      to date there have been two limitations to clinical application of these CRAd
      agents; i.e., both infectivity and tumor specificity are poor. Survivin protein
      is a novel member of the inhibitor of apoptosis (IAP) protein family, which plays
      an important role in the survival of cancer cells and progression of
      malignancies. Previous data have shown the survivin promoter has high activities
      in multiple cancer cells with a low activity in mouse liver. In this study, we
      propose an improved CRAd agent to circumvent the obstacles. We constructed a
      novel CRAd agent, CRAd-Survivin-RGD, which contains both the survivin promoter
      (either the short version, S-S, or the long version, S-L) to selectively drive E1
      gene expression in tumor cells and a capsid modification and RGD4C to
      specifically enhance the tumor infectivity of CRAd agents. Both CRAd agents (S-S
      and S-L) showed high replication rates in the breast cancer cell line, MDA-MB
      361, and low promoter activity in both normal mouse and human liver, thus
      signifying the CRAd agents have the phenotype of 'tumor on/liver off'. In
      cytocidal experiments, the CRAd agents demonstrated a high cytocidal effect on
      multiple cancer cell lines, including the breast cancer cell line, MDA-MB-231;
      the glioma cell line, D65, the melanoma cell line, MEL-28; and mesothelioma,
      Meso2374. The results also showed the tumor growth was dramatically inhibited by
      intertumoral administration of the CRAd agents in a breast cancer (MDA-MB-361)
      xenograft animal model. These data clearly demonstrate that CRAd-Survivin-RGD is
      a potential novel therapeutic agent for treatment in many, but not all, human
      cancers.

PMID- 15942666
TI  - Molecular mechanism of antitumor activity of taxanes in lung cancer (Review).
AB  - Lung cancer is the most common cause of cancer mortality in both male and female
      patients in the United States of America, as well as in the rest of the world.
      Over one million people are diagnosed with lung cancer every year worldwide. The
      taxane is one of the most powerful classes of novel antitumor agents and has
      become an integral part of several commonly used chemotherapy regimens in lung
      cancer management over the past few years. Although the ability of taxanes to
      disrupt microtubule dynamics is well documented, the molecular basis by which
      taxanes suppress cancer cell growth and induce apoptotic cell death is not
      clearly defined. In this review, we focus on the molecular mechanisms of the
      antitumor activity of taxanes (paclitaxel and docetaxel) in lung cancer, and
      discuss the interactions of taxanes with microtubules, the roles of cell cycle
      control and cell death induction in the anticancer action of taxanes, as well as
      the signal transduction pathways involved in the processes. In addition, we
      discuss the possible mechanisms of taxane resistance, because drug resistance to
      these anti-neoplastic agents affects therapy efficacy and is also a major
      obstacle in the clinic for the successful treatment of lung cancer. Understanding
      the molecular mechanisms underlying the antitumor effect of taxanes and the drug
      resistance to taxanes may lead to the design of biologically and
      pharmacologically targeted therapeutic strategies for taxane resistant tumors,
      and to the improvement of chemotherapy effect and cancer patient survival.

PMID- 15942667
TI  - 1H-NMR metabolic markers of malignancy correlate with spontaneous metastases in a
      murine mammary tumor model.
AB  - End-products of glycolysis as well as phospholipid precursors and catabolites
      have been suggested as metabolic indicators of tumor progression. To test the
      hypothesis that increased levels of such indicators can distinguish metastatic
      phenotypes, we determined a limited cellular 1H-NMR metabolic profile of
      subpopulations of murine mammary 4T1 cells that differ in their metastatic
      potential. Subpopulations with differing metastatic phenotypes were identified by
      sorting for the expression of the cell surface adhesion oligosaccharide
      sialylated Lewis x (sLeX). The sLeX-negative subpopulation metastasizes to the
      lung of syngeneic mice more rapidly than the sLeX-positive subpopulations. The
      metabolic profile of the sLeX-negative subpopulation indicated higher levels of
      lactate and total choline metabolites than the sLeX-positive subpopulation,
      suggesting that altered metabolism is a critical component of the malignant
      phenotype. Analysis of shed cellular material from the sLeX-negative
      subpopulation displayed an increased ratio of phosphocholine to
      glycerophosphocholine when compared to the parental line and sLeX-positive
      subpopulation. Serum obtained from mice inoculated with either sLeX-negative or
      sLeX-positive tumor cells contained broader methylene resonances (P = 0.0002; P =
      0.0003) and narrower methyl resonances (P = 0.0013; P < 0.0001) when compared to
      serum of naive mice. However, line widths of methylene and methyl resonances were
      not useful for distinguishing between the two tumor phenotypes. Results of this
      study further support the notion that metabolic indicators of malignancy can
      correlate with in vivo metastatic behavior.

PMID- 15942668
TI  - Use of polyclonal rabbit antibodies for detection of the bcr-abl fusion zone in
      cells transfected with experimental bcr-abl DNA vaccines.
AB  - Rabbits were immunized with peptides covering the fusion zone of the chimeric bcr
      abl protein in order to prepare antibodies capable of detecting the expression of
      a selected portion of this fusion zone, by a variety of experimental genetic
      vaccines. Three peptides of different size covering the b3a2 fusion zone, either
      unmodified or modified by the omission of alanine at the N-terminal of the a2
      section of the fusion zone, and one peptide covering the unmodified b2a2 fusion
      zone were used. All were capable of eliciting antibodies reactive with the
      respective immunizing peptides. Their cross-reactivities, especially the results
      of cross-absorption experiments, strongly suggested that the serum of the rabbit
      immunized with an octadekapeptide mimicking the b3a2 fusion zone contained
      antibodies against a novel antigenic determinant created by the chimeric protein,
      and also against an epitope present in the adjacent a2 section but no antibody
      reactive with the adjacent b3 region. In Western blotting, these antibodies were
      capable of detecting the p210bcr-abl or a portion of it (a 25 amino acid-long
      sequence covering the b3a2 fusion zone) in lysates of 293T cells transfected with
      plasmids that carried either the full cDNA of the bcr-abl gene or a fragment
      thereof fused with either the HSP70 gene or certain other genes.

PMID- 15942669
TI  - Comparative genomics on Dkk1 orthologs.
AB  - WNT family proteins bind to transmembrane proteins FZD1, FZD2, FZD3, FZD4, FZD5,
      FZD6, FZD7, FZD8, FZD9, FZD10, LRP5, LRP6, ROR1, ROR2, RYK, and also secreted
      proteins SFRP1, SFRP2, SFRP3, SFRP4, SFRP5, and DAND4 (CER1). DKK family members
      antagonize WNT binding to LRPs, while SFRP family members antagonize WNT binding
      to FZDs. Here, we identified and characterized rat Dkk1 gene and cow Dkk1 gene by
      using bioinformatics. Rat and cow Dkk1 genes, consisting of four exons, were
      located within AC095296.4 and AC157142.1 genome sequences, respectively. Dkk1
      gene at rat chromosome 1q52 was found to encode a 270-aa protein, showing 94.1,
      81.5, 78.9, 53.7 and 48.1% total-amino-acid identity with mouse Dkk1, human DKK1,
      cow Dkk1, Xenopus dkk1 and zebrafish dkk1, respectively. Vertebrate Dkk1
      orthologs were secreted proteins with two Cys rich regions, each containing ten
      conserved Cys residues. The C-terminal Cys rich region was well conserved among
      vertebrate Dkk1 orthologs. Nucleotide position 148898-147860 of AC009986.10 human
      genome sequence was identified as evolutionarily conserved human DKK1 promoter,
      and nucleotide position 55266-56301 of AC095296.4 rat genome sequence as
      evolutionarily conserved rat Dkk1 promoter. Human DKK1 promoter and rat Dkk1
      promoter, showing 66.2% total nucleotide identity, were well conserved. TCF/LEF,
      CP2, POU2F1 (OCT1), HNF1 and FOXJ2-binding sites and TATA-box were conserved
      among human DKK1, rat Dkk1, mouse Dkk1, and cow Dkk1 promoters. Double TCF/LEF
      binding sites within the proximal promoter region of mammalian Dkk1 orthologs are
      implicated in the negative feed back mechanism of WNT/beta-catenin signaling
      pathway.

PMID- 15942670
TI  - Comparative genomics on mammalian Fgf3-Fgf4 locus.
AB  - The CCND1-ORAOV1-FGF19-FGF4-FGF3-TMEM16A-FADD-PPFIA1-CTTN (EMS1) locus at human
      chromosome 11q13.3 is amplified in head and neck tumors, esophageal cancer,
      Kaposi's sarcoma, bladder tumors, breast cancer, and liver cancer. Fgf4 mRNA is
      expressed in embryonic stem (ES) cells depending on Sox2 and Pou5f1 (Oct3/Oct4)
      transcription factors, and in myotomes and limb bud AER depending on MyoD (or
      Myf5) and GATA transcription factors. Here, rat Fgf3 and Fgf4 complete coding
      sequences were determined by using bioinformatics. Multiple errors, including one
      base insertion and 22-base deletion, were identified within the coding region of
      rat Fgf4 RefSeq (NM_053809.1 or AB079673.1). Rat Fgf3 and Fgf4 genes, consisting
      of three exons, were clustered in tail-to-head manner with an interval of about
      16 kb. CUTL1 (CCAAT-displacement protein, CDP) and NKX2-5 binding sites and TATA
      box within 5'-flanking promoter region were conserved among human, rat and mouse
      Fgf3 orthologs. MYOD and MYOG (Myogenin) binding sites and TATA box within 5'
      flanking promoter region as well as GATA, MYOD, SOX2 and POU5F1 binding sites
      within exon 3 were conserved among mammalian Fgf4 orthologs. Human FGF3 and FGF4
      genes were clustered in tail-to-head manner with an interval of about 35 kb.
      Major repetitive sequence (FGF34Rep1) and minor repetitive sequence (FGF34Rep2)
      were identified within human FGF3-FGF4 gene cluster. FGF34Rep1 were clustered
      within the FGF3-FGF4 locus as well as around the IL28RA locus (1p36.11) and the
      NFAM1 locus (22q13.2). FGF34Rep2 was characterized by the CCA(T/C) repeats. This
      is the first report on comparative genomics analyses on the Fgf3-Fgf4 locus
      within human, rat and mouse genomes.

PMID- 15942671
TI  - Tight junctions and bladder cancer (review).
AB  - Tight junctions play a critical role in the maintenance of the urine-blood
      barrier creating a physiological barrier to the passage of ions and solutes
      between the urine and blood. Alterations in this urine-blood barrier function
      have been demonstrated in some diseases and regulation of the tight junction
      function has been recognised as an important aspect of the cell biology of cancer
      in terms of disease progression and as a potential therapeutic target. Although
      tight junctions play an important role in the physiological control of bladder
      function, there is little published on their molecular composition or regulation
      in the normal or diseased bladder. The purpose of this review is to summarise
      current understanding on the role and regulation of tight junction function in
      the normal and diseased bladder.

PMID- 15942672
TI  - Identification of proteins from colorectal cancer tissue by two-dimensional gel
      electrophoresis and SELDI mass spectrometry.
AB  - We investigated protein profiles obtained from colorectal tumor tissue and
      adjacent normal mucosa to identify tumor specific changes. Protein extracts of
      biopsis were separated by two-dimensional gel electrophoresis and >40 low
      molecular mass proteins were identified by peptide fingerprinting using surface
      enhanced laser desoption/ionization mass spectrometry (SELDI-MS). Among these,
      PACAP protein, hnrnp A1, flavin reductase, calgizzarin, NDK B (NM23-H2),
      cyclophilin A and smooth muscle protein 22-alpha showed significantly
      differential abundancy in the analyzed specimens. In addition,
      immunohistochemical analysis of tissue distribution and subcellular localization
      of some of the differentially expressed proteins demonstrated alterations in
      subcellular protein distribution. Further investigations are in progress to
      assess whether these differentially expressed proteins are associated with tumor
      development and tumor progression.

PMID- 15942673
TI  - Cloning, expression and characterization of human glutathione S-transferase Omega
      2.
AB  - The class of Omega glutathione transferases is newly identified with novel
      structural and functional characteristics. Human GSTO 1-1 (glutathione S
      transferase Omega 1) is the first member of the GST Omega class. It was found to
      play a role in apoptosis and be in association with age-at-onset of AD and PD. In
      order to improve the understanding of the properties of other Omega class
      members, we screened a human fetal brain cDNA library and obtained the human
      GSTO2 (glutathione S-transferase Omega 2) cDNA. The full-length cDNA of human
      GSTO2 is 1179 bp long and encodes a protein of 243 amino acid residues.
      Expression pattern analysis revealed that GSTO2 was ubiquitously expressed at a
      low level, with a higher expression in pancreas and prostate. Enzyme assays
      showed that GSTO2 protein had activities similar to Omega class GSTs. It has
      detectable glutathione-dependent thiol transferase activity and glutathione
      dependent dehydroascorbate reductase activity. But different from GSTO1-1, GSTO2
      exhibits a high catalytic activity with CDNB. Subcellular localization analysis
      of GSTO2-EGFP fusion protein revealed that GSTO2 distributed to cytoplasm of COS
      7 cells and both cytoplasm and nucleus of L-02, QGY-7703 and SMMC-7721 cells.
      Overexpression of GSTO2 induced apoptosis of L-02 cells detected by Annexin V-PE
      staining. The results suggest that GSTO2 may play an important role in cellular
      signaling.

PMID- 15942674
TI  - Drug-induced toxic epidermal necrolysis and pancytopenia: a puzzling association.
AB  - The molecular mechanisms involved in the pathogenesis of toxic epidermal
      necrolysis (TEN) remain not fully understood. We report a unique case of
      antibiotic-induced TEN developed in a patient who also suffered from prolonged
      severe methotrexate-induced pancytopenia. The objective of the study was to
      explore the nature of the cutaneous inflammatory infiltrate and the density in
      dermal dendrocytes (DD). Immunohistochemistry was used to identify activated T
      lymphocytes (CD45R0), monocyte-macrophages (Mac 387, CD68), DD (Factor XIIIa),
      and Langerhans cells (CD1a). The proliferation marker (Ki67) and the antibody to
      Fas receptor (CD95R) were also used to assess the distribution of the germinative
      pool of keratinocytes and the FAS-related apoptotic process, respectively.
      Numerous Factor XIIIa+ DD were present in the papillary dermis with only sparce
      perivascular CD45RO+ T lymphocytes and scattered CD68+ or Mac 387+ macrophages.
      Double immunostainings revealed that a minority of Factor XIIIa+ DD co-expressed
      the CD68 glycoprotein (a marker of phagocytic activity). No cells co-expressed
      factor XIIIa and Mac 387 immunoreactivities. CD45RO+ T lymphocytes, CD68+ and Mac
      387+ macrophages were absent in the epidermis. The expression of CD95R was
      present although restricted to the basal keratinocytes, while the L1-protein (Mac
      387+) was diffusely present in the epidermis. Langerhans cells (CD1a+) were
      sparce, but normal in distribution. The presence of a great number of Factor
      XIIIa+ DD without any possible recent recruitment from bone marrow suggests that
      these cells differentiated from resident cells of the skin. Indeed, there was no
      co-expression of Factor XIIIa and L1-protein, thus showing the absence of
      recruitment from monocytes. The simultaneous over-expression of Factor XIIIa and
      CD68 in some DD indicates some phagocytic activity. In view of the absence of
      inflammatory cells in the epidermis, keratinocytes appeared responsible for their
      own destruction through CD95-mediated and/or calcium-dependent apoptotic
      pathways. This finding entails that TEN treatments should target the keratinocyte
      metabolism rather than the circulating inflammatory cells which presumably play a
      limited role, if any, in the epidermal destructive process.

PMID- 15942675
TI  - Differential expression and function of beacon in the rat adrenal cortex and
      medulla.
AB  - Beacon gene is overexpressed in obese rats, and beacon was found to stimulate
      food intake. Evidence has been recently provided that beacon is also expressed in
      the endocrine glands of normal rats, including adrenal cortex, of which it
      appears to regulate secretory activity. To further characterize the role of
      beacon in the rat adrenals, we investigated the level of beacon expression in the
      adrenal zona glomerulosa (ZG), zona fasciculata-reticularis (ZF/R) and medulla
      (AM), and the in vitro secretory responses to beacon[47-73] (hereinafter, beacon)
      of adrenocortical and adrenomedullary tissues. Real-time polymerase chain
      reaction revealed similar high levels of beacon mRNA in the ZG and ZF/R, and
      significantly lower (-80%) levels in AM. Immunocytochemistry showed that the
      distribution of beacon protein followed that of beacon mRNA. Quantitative high
      pressure liquid chromatography demonstrated that beacon (5x10(-7) M) reduced by
      about 56% the in vitro total steroid-hormone production from ZG and ZF/R tissues,
      without affecting catecholamine secretion from AM specimens. The beacon-induced
      lowering in the secretory activity of adrenal cortex depended on similar
      reductions (from 50-64%) in the production of the main adrenocortical hormones
      (pregnenolone, progesterone, 11-deoxycorticosterone, corticosterone, 18-hydroxy
      corticosterone and aldosterone), thereby suggesting an inhibitory action of
      beacon in the early step of steroidogenesis (i.e. the conversion of cholesterol
      to pregnenolone). The hypothesis is advanced that beacon is to be considered an
      autocrine-paracrine negative regulator of mineralo- and glucocorticoid synthesis
      in the rat adrenal gland.

PMID- 15942676
TI  - Regulatory effects of emodin on NF-kappaB activation and inflammatory cytokine
      expression in RAW 264.7 macrophages.
AB  - Emodin, an anthraquinones component of Rheum palmatun, has been used for anti
      inflammatory purposes. However, its underlying molecular effect(s) on target
      cells remain to be well clarified. Thus, our current study was aimed at
      investigating the regulatory mechanism of emodin on liposaccharide-induced
      inflammatory responses in RAW 264.7 macrophages by RT-PCR, Western blot analysis,
      immunocytochemical staining and immunofluorescence analysis. It was found that a
      treatment of 20 microg/ml emodin inhibited the expression of a panel of
      inflammatory-associated genes, including TNFalpha, iNOS, IL-10, cytosolic
      IkappaBalpha, IKK-alpha and IKK-gamma, to different extents as well as the
      nuclear translocation of NF-kappaB (nuclear factor-kappaB). The promoting effect
      of emodin on the production and translocation of p105 (the precursor of NF-kappaB
      p50) was time-dependent and reached a maximum at 5 h. Our data suggest that
      emodin plays its anti-inflammatory roles by regulating inflammatory cytokines,
      specifically by suppressing NF-kappaB activation.

PMID- 15942677
TI  - Direct effect of plasma permeability factors from patients with idiopatic FSGS on
      nephrin and podocin expression in human podocytes.
AB  - The presence of circulating plasma factors (PF) altering renal permeability to
      proteins has been previously described in patients with focal segmental
      glomerulosclerosis (FSGS). Since these patients show reduced nephrin and podocin
      expression at renal biopsy, we evaluated the effect of serum and PF from patients
      with FSGS on nephrin and podocin expression in human podocytes. We studied 7 sera
      from patients with steroid-resistant FSGS, 3 from patients with nephrotic
      syndrome caused by non-immune disease, and 6 from healthy subjects. PF was
      prepared from plasmapheresis eluates of 2 patients with post-transplant
      recurrence of FSGS. Purification procedure was based on protein A Sepharose
      chromatography and differential precipitation in ammonium sulphate. Nephrin and
      podocin expression was semi-quantitatively evaluated by immunofluorescence. We
      found that serum and PF from FSGS patients rapidly induced redistribution and
      loss of nephrin in podocytes. This effect was associated with cytoskeleton
      redistribution and inhibited by cytochalasin B and sodium azide. On the contrary,
      podocin expression was unchanged after incubation with serum and PF from FSGS
      patients for short periods, but markedly reduced at 24 h. Our results demonstrate
      that serum and PF from FSGS patients may directly affect nephrin and podocin in
      human podocytes, thus providing new insights into the mechanisms causing
      proteinuria in FSGS.

PMID- 15942678
TI  - Remote delivery and expression of soluble type II TGF-beta receptor in muscle
      prevents hepatic fibrosis in rats.
AB  - Transforming growth factor-beta (TGF-beta) has been implicated in the process of
      hepatic fibrosis, and stimulates production of extracellular matrix in hepatic
      stellate cells, which play a major role in the process. It has been recently
      reported that blockage of TGF-beta signaling prevents hepatic fibrosis. We
      evaluated a strategy for anti-TGF-beta gene therapy for hepatic fibrosis by
      transfecting plasmids expressing an entire extracellular domain of human TGF-beta
      type II [soluble type II TGF-beta receptor (sTGF-betaIIR)] into skeletal muscle
      in a rat experimental model of dimethylnitrosamine- (DMN-) induced fibrosis. sTGF
      betaIIR treatment decreased significantly the occurrence of DMN-induced hepatic
      fibrosis, evaluated by computed image analysis and by measurement of
      hydroxyproline content of the liver, and reduced the expression of collagen and
      alpha-smooth muscle actin. The treatment also caused a significant decrease in
      hepatic levels of interleukin- (IL-) 12 (Th1 cytokine) and an increase in those
      of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in
      the liver. In conclusion, blockade of TGF-beta after intramuscular transfer of
      the soluble type II TGF-beta receptor gene suppressed hepatic fibrosis,
      suggesting that this strategy may be useful for gene therapy of hepatic fibrosis.

PMID- 15942679
TI  - Generation and characterization of iBREC: novel hTERT-immortalized bovine retinal
      endothelial cells.
AB  - Primary retina-derived endothelial cells isolated from bovine and other animal
      tissues are extremely useful for studying the molecular mechanisms involved in
      the pathogenesis of diabetic retinopathy. Preparations of primary bovine retinal
      endothelial cells (BREC), however, usually contain a number of contaminating non
      endothelial cells, e.g. pericytes which have been shown to inhibit proliferation
      of endothelial cells. To overcome this major drawback, we immortalized BREC by
      reconstitution of telomerase activity as a consequence of CMV promoter-driven
      expression of the catalytic domain of human telomerase. Immortal BREC (iBREC)
      have the capacity to proliferate for >90 passages over 10 months and constantly
      express endothelial marker proteins. In addition, iBREC behave like BREC with
      respect to stimulation of proliferation with VEGF, IGF-1 and bFGF, indicating
      that we have generated a stable endothelial cell line closely related to the
      corresponding primary cells.

PMID- 15942680
TI  - Cytokine-induced neutrophil accumulation in the pathogenesis of acute reflux
      esophagitis in rats.
AB  - Although recent reports indicate an increasing incidence of patients with reflux
      esophagitis, its pathomechanism remains unclear. Cytokines and neutrophils, the
      latter of which produce reactive oxygen species (ROS), have been implicated in
      the formation of gastrointestinal diseases. This study investigated the roles of
      neutrophils, ROS, and cytokines in the pathogenesis of experimental reflux
      esophagitis. Esophagitis was induced in male Wistar rats by ligation at both the
      limiting ridge of the stomach and lower portion of the duodenum. The esophagus
      was then removed, and the lesion index, wet weight, thiobarbituric acid-reactive
      substances (an index of lipid peroxidation), myeloperoxidase activity (an index
      of neutrophil accumulation), tumor necrosis factor-alpha (TNF-alpha), and
      cytokine-induced neutrophil chemoattractant (CINC)-1 in the esophageal mucosa
      were estimated, and a histological study (hematoxylin-and-eosin staining) was
      performed. The mRNA expression of TNF-alpha and CINC-1 was analyzed. Anti
      neutrophil serum (ANS) was injected intraperitoneally prior to the induction of
      esophagitis, and inflammatory markers were estimated as described above. The
      values of all markers increased, and the histological study revealed neutrophil
      infiltration and edema in mucosa and submucosa at both 12 and 18 h after
      induction. However, the mRNA expression of both cytokines was observed earlier at
      3 and 6 h after induction. ANS inhibited the increases in all inflammatory
      markers. These results indicate that ROS and lipid peroxidation mainly derived
      from neutrophils, which are stimulated and mobilized by TNF-alpha and CINC-1, are
      implicated in the pathogenesis of esophageal inflammation induced by the reflux
      of gastroduodenal contents.

PMID- 15942681
TI  - Frequent apoptosis in placental villi from pregnancies complicated with
      intrauterine growth restriction and without maternal symptoms.
AB  - The objective of this study was to examine the incidence of apoptosis in
      placentas of intrauterine growth restriction (IUGR) without maternal disease. We
      focused on cases of IUGR with both unknown causes and no maternal complications.
      In addition, apoptosis of IUGR placentas was correlated with the expression of
      proteins involved in apoptosis and cell turnover. The term placentas were
      obtained from 16 normal and 10 IUGR pregnancies without maternal symptoms. We
      analyzed the localization of apoptosis and counted >2000 nuclei by TUNEL assay
      and transmission electron microscopy in placentas from normal and IUGR cases. We
      found the incidence of apoptosis to be significantly higher in placentas with
      IUGR (2.98%) than in normal placentas (1.46%) by TUNEL assay (p=0.03). In
      addition, immunohistochemical analysis was performed to examine the expression of
      proteins related to apoptosis and general cell turnover, including the active
      form of caspase-3, Bax, p53, and Ki-67. Expression of the active form of caspase
      3 was significantly higher in IUGR than in a normal pregnancy (p=0.03). These
      results suggest that enhanced execution of apoptosis through caspase-3 may play a
      role in IUGR without maternal symptoms.

PMID- 15942682
TI  - Aberrations of the CHK2 gene are rare in pediatric solid tumors.
AB  - In pediatric solid tumors, such as neuroblastoma (NB), it has been reported that
      the frequency of TP53 gene alterations is lower than that in adult tumors,
      suggesting that other tumor suppressor genes may play more important roles in the
      development of pediatric solid tumors. The CHK2 gene, whose product is a
      checkpoint kinase that plays a central role in DNA damage response and acts
      upstream of TP53, has been found to be mutated in a subset of Li-Fraumeni
      syndrome without mutations of TP53 and in some other sporadic human tumors,
      earmarking this serine/threonine kinase as a candidate tumor suppressor gene.
      Thus, we analyzed the CHK2 gene to address whether it is a candidate tumor
      suppressor gene for pediatric solid tumors. We screened for mutations of the CHK2
      gene in 25 NB, 8 rhbdomyosarcoma, 12 Ewing sarcoma, and 26 other pediatric solid
      tumor cell lines as well as 77 fresh tumors including two cases of multiple
      cancers. Using polymerase chain reaction-single-strand conformation polymorphism
      (PCR-SSCP) analysis and reverse transcriptase (RT)-PCR-SSCP followed by direct
      sequence analysis, we detected only one missense mutation (S505T) in one NB cell
      line and two silent mutations in one NB cell line and one NB fresh tumor,
      respectively. Through RT-PCR and subcloning analysis, we detected a similar
      expression of the CHK2 gene in all of the NB cell lines and fresh tumors;
      however, we identified at least three isoforms of the CHK2 gene, two of which
      have not been reported previously. These results suggest that aberrations of the
      CHK2 gene are rare in pediatric solid tumors.

PMID- 15942683
TI  - Fine deletional mapping of chromosome 4q22-35 region in oral cancer.
AB  - We analyzed the loss of heterozygosity of the long arm of chromosome 4 in 40 oral
      cancers, using 16 microsatellite markers based on data from the human genome
      sequence, and defined the deletional mapping of the region with putative tumor
      suppressor genes. Our data revealed two distinct commonly deleted regions around
      the markers, D4S2623 and D4S1644, with an allelic deletion of 44 and 39%,
      respectively. Additional mapping and use of the markers near one of these hot
      spots narrowed down the minimally deleted region about 1.5 Mbp around the marker,
      D4S2623. Caspase 6 is localized 280 kb from the marker, D4S2623. Fine mapping of
      this region with possible tumor suppressor gene suggests caspase 6 as a putative
      tumor suppressor gene. Further molecular analysis of caspase 6 should be
      performed to clarify its role in oral carcinogenesis.

PMID- 15942684
TI  - The anti-inflammatory effects of 2 Hz electroacupuncture with different
      intensities on acute carrageenan-induced inflammation in the rat paw.
AB  - The aim of this study was to investigate the anti-inflammatory effects of low
      frequency electroacupuncture (EA) with different intensities in carrageenan
      injected rat paw. Bilateral 2 Hz EA stimulation with 0.5, 1 and 3 mA were
      delivered at those acupoints corresponding to Zusanli and Sanyinjiao in man via
      needles for 30 min. We first examined the degrees of edema and hyperalgesia using
      measurements of paw swelling and hot plate latency over 180 min, at 30 min
      intervals, after the carrageenan injection. The edema and thermal sensitivities
      of the hind paw induced by a carrageenan-injection were strongly inhibited by EA
      stimulation, especially at low intensity. At 3 h after carrageenan-injection, we
      investigated whether the effects of a 2 Hz EA on a carrageenan-induced edema and
      hyperalgesia are associated with peripheral cyclooxygenase (COX) mRNA induction
      and prostaglandin E2 (PGE2) synthesis. Although the induction of COX-2 mRNA was
      inhibited by 2 Hz EA at various intensities, there was no significant change.
      However, the synthesis of PGE2 induced by a carrageenan injection was
      significantly attenuated in rat paw with low intensity EA treatment. The data
      indicate that low frequency EA treatment with relatively low intensity might be a
      useful therapy for mitigation of inflammatory edema and hyperalgesia through the
      regulation of COX-2 expression and PGE2 production in a model of peripheral
      inflammation in rats.

PMID- 15942685
TI  - Roles of His9 (P2 subsite) and His13 (P3' subsite) in angiotensinogen for
      catalytic reaction of renin.
AB  - Roles of His9 (P2) and His13 (P3') of angiotensinogen for the catalytic reaction
      of renin were investigated using purified recombinant ovine angiotensinogen and
      its mutants H9Q and H13Q. The pH depended reaction of human renin with
      angiotensinogens of wild-type, H9Q and H13Q showed peaks at pH 6.5 and 8.5, but
      the altitude of each peak was different. The Vmax of the reaction between H9Q and
      H13Q with human renin was decreased by about 50 and 70%, respectively, in
      comparison to wild-type angiotensinogen, at pH 6.5. At pH 8.5, the Vmax of H9Q
      and H13Q was 50 and 100% of that of wild-type, respectively. At pH 6.5, it was
      revealed that the catalytic efficiency of renin (Vmax/Km) reduced to 20 and 60%
      after mutation of angiotensinogen at His9 and His13 with Gln, respectively. At pH
      8.5, the catalytic efficiency decreased to 10 and 70% after these mutations,
      respectively. These findings, therefore, indicate that histidine residues at both
      P2 and P3' positions probably associate with the renin catalytic reaction for
      angiotensin I generation.

PMID- 15942686
TI  - Causal relationship between hepatitis C virus core and the development of type 2
      diabetes mellitus in a hepatitis C virus hyperendemic area: a pilot study.
AB  - Hepatitis C virus (HCV) infection may contribute to the development of type 2
      diabetes mellitus. However, this association at the population level remains
      unclear. The aim of this pilot study is to examine the relationship between HCV
      infection and the development of type 2 diabetes mellitus in an HCV hyperendemic
      area where we conducted health screenings in 1995. After 7 years of follow-up, we
      evaluated the relative risk of the development of type 2 diabetes mellitus in
      anti-HCV-inhabitants. Among 71 subjects free of diabetes mellitus in 1995, 7
      developed type 2 diabetes mellitus during the 7-year follow-up evaluation.
      Overall, anti-HCV-positive subjects were nearly 3-fold as likely as anti-HCV
      negative subjects to develop diabetes mellitus, but this difference was not
      statistically significant (p=0.08). After stratification of the anti-HCV-positive
      group according to serum HCV core titer, a significant increase in the incidence
      of diabetes was seen in subjects with high titer of HCV core compared to anti-HCV
      negative subjects (p=0.02; relative hazard, 5.60; 95% confidence interval, 1.41
      to 37.42). In conclusion, HCV infection potentially has a significant role in the
      development of type 2 diabetes mellitus at the population level. Further large
      scale studies are needed to confirm these preliminary findings.

PMID- 15942687
TI  - Semaphorin 4A induces growth cone collapse of hippocampal neurons in a Rho/Rho
      kinase-dependent manner.
AB  - Semaphorins are a family of secreted and membrane-bound proteins, known to
      control axonal pathfinding. It was recently demonstrated that Semaphorin 4A
      (Sema4A) is crucially involved in immune cell activation. However, the role of
      Sema4A in the nervous system has not yet been clarified. To examine if Sema4A can
      function as a chemo-repulsive cue to growth cones of developing hippocampal
      neurons, a growth cone collapse assay with recombinant Sema4A was performed in
      primary hippocampal neurons cultured from E17 mice. In these primary hippocampal
      neurons, Sema4A induced a significant growth cone collapse as compared with the
      culture without Sema4A. The Sema4A-induced growth cone collapse could be blocked
      by Y-27632, a Rho-kinase inhibitor. Furthermore, immunocytochemical analysis with
      antibodies against Sema4A demonstrated the binding of recombinant Sema4A to the
      growth cones of hippocampal neurons. Thus, our data indicated that Sema4A could
      function as a chemo-repulsive cue by activating a receptor whose signal is
      transmitted to Rho-kinase and induced growth cone collapse of hippocampal
      neurons.

PMID- 15942688
TI  - Evidence of dual function of macrophage migration inhibitory factor relevant to
      tumor progression and regression.
AB  - Macrophage migration inhibitory factor (MIF) is known to play an important role
      in broad-spectrum inflammation and immune responses. To evaluate the role of MIF
      in tumor growth, we established transgenic (Tg) mice (ICR strain) driven by
      cytomegalovirus (CMV) enhancer and beta-actin promoter. We inoculated Tg mice in
      the back with murine sarcoma cell line S-180 cells. The tumor growth rate was
      more enhanced in Tg mice than in littermate non-Tg mice up to day 9 after tumor
      inoculation. Surprisingly, most tumors embedded on the back of Tg mice regressed
      at day 10 after inoculation and eventually disappeared. Tumor volumes of non-Tg
      mice incessantly increased until death. We reinoculated the Tg mice with S-180
      cells, which had been recovered from the first challenge, and found that the
      tumor cells were completely rejected in all cases. To identify the effector cells
      that eradicated the tumor cells, we prepared spleen cells from tumor-bearing Tg
      mice and carried out cell lysis assay. The magnitude of cytolytic activity of
      spleen cells obtained from Tg mice was significantly higher against S-180 cells,
      as well as natural killer cell-sensitive YAC-1 cells, than was the activity of
      cells from non-Tg mice. Furthermore, we observed that CTL activity of Tg mice
      against S-180 cells was significantly decreased by the deletion of CD8+ T cells
      or NK cells. On the other hand, the deletion of CD4+ cells minimally affected the
      cytolytic activity. Taken together, these results suggest that MIF has the
      potential to promote tumor growth and angiogenesis in the early phase and, by
      contrast, this protein could activate CD8+ cytotoxic T cells and NK cells,
      leading to tumor regression.

PMID- 15942689
TI  - Two secretory immune systems (mucosal and barrier) in human intrauterine
      development, normal and pathological (Review).
AB  - The role of protein components of the secretory immune system (SIS), such as the
      polymeric immunoglobulin receptor/secretory component (pIgR/SC), immunoglobulins
      (Igs) and joining (J) chain, in human intrauterine development was reviewed.
      These components are already present in 3.5- to 4-week-old embryos, and found in
      all tissues and organs of epithelial origin. The SIS is made up of two parts: the
      SIS of mucous membranes and their derivatives (mucosal or secretory immune
      system), and the SIS of barrier structures (barrier immune system). During
      organogenesis, SC disappears from the cells of organs that lose their exocrine Ig
      secretion function, such as the hypophysis, pancreatic islands and adrenal
      glands. In cells and tissues of mesenchymal origin, SC is absent from the start,
      i.e. during their initial development. As examples of the barrier immune system,
      blood-tissue and tissue-tissue barriers, such as the chorion of the placenta, the
      epithelium of the choroid plexuses in the brain, as well as other barrier
      structures to Ig transfer were considered. Besides the SC and J chain, Fc
      receptors, cellular and tissue structures participate in this process. Three
      stages were described in Ig transfer: i) passing from the maternal blood into
      intervillous spaces and the trophoblast, ii) shifting in the intravillous stroma
      and its cells, and iii) excretion into embryonic (fetal) blood through the
      endothelium of the trophoblastic villous capillaries. Igs of maternal origin,
      mainly IgG and least abundant IgA, pass through the placental barrier in healthy
      embryos. Following a massive antigenic attack, the increased exocrine secretion
      of IgG, IgA, and IgM to a lesser extent, are already seen in embryos, reflecting
      increased functional activity of the SIS. Thus, in human intrauterine
      development, the SIS is a very early immune defensive system, which presents and
      acts before the appearance of the common lymphoid system.

PMID- 15942690
TI  - CGH analysis of familial non-BRCA1/BRCA2 breast tumors and mutation screening of
      a candidate locus on chromosome 17q11.2-12.
AB  - Mutations in the known predisposing breast cancer genes BRCA1 and BRCA2 account
      for only a small proportion (<10%) of breast cancer families in the Stockholm
      region of Sweden. This study aims to identify novel predisposing genes in non
      BRCA1/BRCA2 breast cancer families. We have employed comparative genomic
      hybridization (CGH) and loss of heterozygosity (LOH) data in combination with
      data from a recently carried out genome wide linkage scan, in an effort to
      identify chromosomal regions harboring potential breast cancer genes. CGH
      revealed loss of chromosome 17 and chromosome 6q to be a frequent event in high
      risk breast cancer families, while gain of 8q was most prevalent in low-risk
      families. The loss of chromosome 17 was consistent with previous LOH studies and
      so this region was investigated further. Disease was shown to be linked to
      chromosome 17 in those families exhibiting loss of the chromosome in both CGH and
      LOH analyses. An overlapping region of linkage was determined to lie between
      markers D17S1294 and D17S1293, fine mapping of the region delineated a region
      between markers D17S1880 and D17S1293. Ten genes were determined to lie within
      this 1.5 Mb region and families were screened for germline mutations in these
      genes. In conclusion, we have investigated one possible small region on
      chromosome 17 for its involvement in high-risk non-BRCA1/BRCA2 breast cancer
      families. No predisposing mutations were identified in the 10 genes investigated
      in this study, however further analysis of chromosome 17 is warranted.

PMID- 15942691
TI  - Kinetic fluorescence RT-PCR is highly sensitive for detection of germ-cell-tumor
      specific transcripts in peripheral blood.
AB  - The aim of our study was to determine whether conventional staging in patients
      with testicular germ-cell-tumors (GCT) could be supplemented by quantification of
      beta-human choriogonadotropin mRNA levels in peripheral blood using kinetic
      fluorescence RT-PCR. Blood samples from 41 patients with GCT of different
      clinical stages (CS) were pre-therapeutically examined by kinetic fluorescence RT
      PCR with the LightCycler for beta-human chorionic gonadotropin (beta-HCG) mRNA
      expression levels. The controls comprised of samples taken from patients 3 months
      after treatment, from patients with inflammatory testicular diseases or non-germ
      cell-tumors and from healthy males (n=66). Six positive results [cut-off level:
      normalized beta-HCG mRNA (Nbeta-HCG) >400 relative gene expression (RGE)] were
      found in controls (specificity 90.9%, 95% CI: 76.9-97.3%). The overall ratio of
      positive PCR results in the group of GCT patients was 82.92% (34/41) (CS I 18/23,
      CS IIa-b 6/7, CS >IIb 10/11) (sensitivity 82.9%, 95% CI: 65.1-91.2%). The average
      Nbeta-HCG level in patients with clinical stage I tumors was 63772.0+/-125720.5
      (mean +/- standard deviation) relative gene expression (RGE), 35076.0+/-52253.5
      RGE in those with CS IIa-b tumors and 87298.3+/-120895.3 RGE in those with CS
      >IIb tumors. Kinetic fluorescence RT-PCR for tumor-specific gene products is, in
      contrast to qualitative RT-PCR, a promising approach to improve conventional
      staging in clinical low-stage testicular germ-cell-tumors. With high specificity,
      its sensitivity is higher than that of the corresponding serum tumor marker
      (82.92% vs 48.72%).

PMID- 15942692
TI  - The influence of lidocaine and verapamil on the proliferation, CD44 expression
      and apoptosis behavior of human chondrocytes.
AB  - Ion channels, which are responsible for the controlled functioning of many cell
      biological processes, are present on the cell membrane of all living human cell
      systems under physiological conditions. A relationship between ion channel
      activity and proliferation behavior has been demonstrated in various cell
      systems. We showed in earlier studies that there is a resting membrane potential
      in the cell membranes of human chondrocytes, which can be influenced by various
      ion channel modulators. The question is to what extent can specific modulation of
      the ion channel activity regulate proliferation, CD44 expression and the
      apoptosis behavior of human chondrocytes. Human chondrocytes were isolated from
      osteoarthritic knee joint cartilage. The culture was made as a monolayer in RPMI
      medium with the addition of 10% fetal calf serum, 50 microg/ml gentamycinsulfate
      and 2 microg/ml amphotericin B at 37 degrees C and 5% carbon dioxide. The voltage
      dependent Na+ channel blocker, lidocaine, and the calcium antagonist, verapamil,
      were used as ion channel modulators. Proliferation was determined using 3H
      thymidine incorporation as the measure. Proof of the CD44 membrane protein was
      performed by flow cytometry with an FITC-conjugated CD44 antibody (anti-CD44H
      FITC). For apoptosis detection, the translocation of phosphatidylserine (Annexin
      V-FITC assay), Apo2.7 and the Caspase activity on cytokeratin 18 were determined
      by flow cytometry. The results show that proliferation behavior can be regulated
      by lidocaine and verapamil, whereby lidocaine results in a transient increase in
      3H-thymidine incorporation. Both substances resulted in marked suppression of
      proliferation after longer incubation times. At the same time, no influence of
      lidocaine could be determined on the apoptosis of human chondrocytes, whereas
      marked cytotoxic effects occurred under verapamil. With respect to CD44 receptor
      expression, incubation with lidocaine resulted in an increase of up to 43%, while
      suppression of up to 56% was observed with verapamil. The possibility of specific
      modulation of ion channel activity on the cell membrane of human chondrocytes may
      serve as the basis for development of new therapeutic options for the treatment
      of arthrosis.

PMID- 15942693
TI  - Vascular endothelial growth factor and basic fibroblast growth factor are
      released by squamous cell carcinoma cells after irradiation and increase
      resistance to subsequent irradiation.
AB  - We analysed the release of vascular endothelial growth factor (VEGF) and basic
      fibroblast growth factor (bFGF) from squamous cell carcinoma (SCC) after
      irradiation and their potential contribution to radiation resistance. Three SCC
      cell lines were irradiated, and VEGF- and bFGF-release was quantified by Elisa
      assay. Conditioned media (CM) were used in clonogenic assays for analysis of
      tumor cell survival. To evaluate the effect of tumor released VEGF and bFGF on
      survival, experiments with neutralizing monoclonal anti-VEGF and anti-bFGF
      antibodies were conducted in parallel. Cell cultures were irradiated with 2 Gy to
      analyse the effects of CM on tumor cell escape from radiation-induced death. We
      observed a marked increase in VEGF- and bFGF-release after irradiation by the
      surviving cells. Using these conditioned media, subsequently we observed an up to
      10-fold increase in colony formation. The addition of anti-VEGF- and anti-bFGF
      antibodies reduced colony formation, indicating that irradiation stimulates the
      release of growth promoting substances including VEGF and bFGF by the surviving
      cells. Additionally, irradiation of cells cultured with CM decreased colony
      formation about 50%, however, it was still increased 5-fold compared to the
      cultures without CM. The addition of VEGF- and/or bFGF-antibodies led to an
      additional 20% reduction of this radioprotective effect of the CM. This means,
      bFGF and VEGF contribute to a significant proportion of the survival stimulating
      activity. We thus show that irradiation might result in autologous protection of
      tumor cells from irradiation-induced cell death by the release of growth factors.
      These observations suggest that radiation might lead to unsuspected and undesired
      effects in tumorous tissue with possible clinical impact.

PMID- 15942694
TI  - Antibodies raised against N'-terminal Pseudomonas aeruginosa flagellin prevent
      mortality in lethal murine models of infection.
AB  - The goal of this study was to investigate if antibodies raised against N'
      terminal Pseudomonas aeruginosa (Pa) flagellin could afford protection in two
      lethal mouse models of Pa infection. To that end, rabbit polyclonal antibodies
      were generated against the N'-terminal domains (amino acids 1-156) of recombinant
      Pa01 or Salmonella muenchen flagellins, termed anti-N'-fla-b and anti-N'-fla-Sm,
      respectively. In vitro, anti-N'-fla-b but not anti-N'-fla-Sm IgG specifically
      recognized recombinant and Pa endogenous flagellin type b proteins, total
      bacterial lysates of Pa type b, and inhibited Pa01 invasion into A549 cells. In
      vivo, administration of anti-N'-fla-b afforded a remarkable improvement in
      survival in lethal peritonitis (90% vs. 12% in control; p<0.001) and burn
      infection (83% vs. 8-17% in control groups; p<0.005) Pa models. These findings
      would suggest that the N'-terminal domain of Pa flagellin harbors critically
      important bioactive domains and that an antibody-targeted, neutralization
      approach directed at this region could provide a novel therapeutic strategy to
      combat Pa infection.

PMID- 15942695
TI  - Combined periprocedural evaluation of CRP and TNF-alpha enhances the prediction
      of clinical restenosis and major adverse cardiac events in patients undergoing
      percutaneous coronary interventions.
AB  - To assess the value of serial C-reactive protein (CRP), serum amyloid A (SAA),
      tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) evaluation in
      the risk stratification in patients undergoing percutaneous coronary
      intervention. The study was designed as a prospective cohort trial with a 1-year
      follow-up. Eighty patients (70 with stable angina, 10 with unstable angina) were
      enrolled. Blood samples were collected before the procedure and after 6 and 24 h,
      and 1 month. Clinical follow-up visits were performed (*with exercise test) 7
      days* and 1*, 3, 6* and 12 months after the procedure. Any symptoms of restenosis
      were verified angiographically. Multivariate logistic regression analysis
      identified increased preprocedural TNF-alpha and CRP levels and elevated CRP
      concentrations evaluated 24 h after the procedure as significant predictors of
      both clinical restenosis and major adverse cardiac events (MACE), while high SAA
      values at 24 h accurately predicted clinical restenosis. Patients, who were in
      the highest tertile of, either, baseline TNF-alpha and/or baseline CRP/CRP at 24
      h, were more prone to develop restenosis and MACE than stratified only on the
      basis of a single marker. Our data indicate that combined analysis of CRP and TNF
      alpha might be an effective approach to the clinical restenosis and MACE
      prediction. Additionally, long-term outcome is markedly influenced by the
      periprocedural activation of inflammation.

PMID- 15942696
TI  - Comparative genomics on Shisa orthologs.
AB  - WNT signaling molecules are implicated in a variety of human tumors, such as
      gastric cancer and colorectal cancer. FGFR2 gene, encoding FGF receptor 2, is
      amplified in human gastric and breast cancer. WNT and FGF signaling pathways
      network together during carcinogenesis and embryogenesis. Xenopus shisa is
      claimed to inhibit the post-translational maturation of wnt and fgf receptors.
      Here, we identified and characterized the rat Shisa (Tmem46) gene by using
      bioinformatics for comparative proteomics and comparative genomics analyses. Rat
      Shisa gene, consisting of two exons, was located within AC126002.4 genome
      sequence. Shisa gene at rat chromosome 15p12 was found to encode a type I
      transmembrane protein (295 aa), showing 99.3, 92.5, 81.7, 40.3 and 38.6% total
      amino-acid identity with mouse Shisa, human SHISA, chicken shisa, Xenopus shisa
      and zebrafish shisa, respectively. The extracellular Cys-rich domain with eight
      Cys residues was conserved among vertebrate Shisa orthologs. The C-terminal
      cytoplasmic region was conserved among mammalian and chicken Shisa orthologs, but
      not in Xenopus and zebrafish Shisa orthologs. Human SHISA promoter and rat Shisa
      promoter were not conserved well. Function of human SHISA is predicted to be
      divergent from that of Xenopus shisa due to the protein evolution and the
      promoter evolution. This is the first report on the rat Shisa gene and on
      molecular evolution of Shisa orthologs.

PMID- 15942697
TI  - Sodalis glossinidius (Enterobacteriaceae) and vectorial competence of Glossina
      palpalis gambiensis and Glossina morsitans morsitans for Trypanosoma congolense
      savannah type.
AB  - Sodalis glossinidius is an endosymbiont of Glossina palpalis gambiensis and
      Glossina morsitans morsitans, the vectors of Trypanosoma congolense. The presence
      of the symbiont was investigated by PCR in Trypanosoma congolense savannah type
      infected and noninfected midguts of both fly species, and into the probosces of
      flies displaying either mature or immature infection, to investigate possible
      correlation with the vectorial competence of tsetse flies. Sodalis glossinidius
      was detected in all midguts, infected or not, from both Glossina species. It was
      also detected in probosces from Glossina palpalis gambiensis flies displaying
      mature or immature infection, but never in probosces from Glossina morsitans
      morsitans. These results suggest that, a) there might be no direct correlation
      between the presence of Sodalis glossinidius and the vectorial competence of
      Glossina, and b) the symbiont is probably not involved in Trypanosoma congolense
      savannah type maturation. It could however participate in the establishment
      process of the parasite.

PMID- 15942698
TI  - Bacterial biofilm development on hydroxyapatite-coated glass.
AB  - Glass plates are frequently used as the substratum in flow cell experiments to
      allow continuous non-destructive observations of biofilm development via
      microscopy. The aim of this study was to evaluate hydroxyapatite-coated glass as
      a substratum for flow cell experiments, in comparison to plain glass, for
      modelling primary colonization of the tooth surface by Streptococcus sanguis.
      Glass plates were magnetron sputter coated with hydroxyapatite, producing a thin
      transparent layer. Biofilm development in the flow cell was recorded using image
      capture from a microscope, and images were analyzed to determine percentage
      coverage of the substratum over 24 h. Removal of biofilm by increasing the flow
      rate was also assessed. No statistically significant differences were detected
      between S. sanguis biofilms grown on the two different substratum materials.
      Hence, this work supports the proposal that the conditioning film reduces the
      influence of substratum surface properties.

PMID- 15942699
TI  - Identification of cry-type genes on 20-kb DNA associated with Cry1 crystal
      proteins from Bacillus thuringiensis.
AB  - Heterologous DNA fragments (20-kb) associated with Cry1 crystal proteins
      (protoxins) from a soil-isolated Bacillus thuringiensis strain 4.0718 were
      isolated and analyzed. RFLP patterns of the PCR products showed that the 20-kb
      DNA fragments harbored cry1Aa, cry1Ac, cry2Aa, and cry2Ab genes. Furthermore, a
      4.2-kb DNA fragment, which contained the promoter, the coding region, and the
      terminator of cry1Ac gene, was cloned from the 20-kb DNAs by PCR, and then the
      cry1Ac gene was expressed in an acrystalliferous B. thuringiensis strain 4Q7 by
      using E. coli-B. thuringiensis shuttle vector pHT3101. SDS-PAGE and microscopy
      studies revealed that the recombinant could express 130-kDa Cry1Ac protoxin and
      produce bipyramidal crystals during sporulation. Bioassay results proved that
      crystal-spore mixture from the recombinant was toxic to Plutella xylostella. This
      was the first report of cry-type genes present on 20-kb DNA associated with Cry1
      protoxins of B. thuringiensis.

PMID- 15942700
TI  - Bacterial species diversity in cigarettes linked to an investigation of severe
      pneumonitis in U.S. Military personnel deployed in operation iraqi freedom.
AB  - This report presents results from a study on the bacterial diversity of cigarette
      brands collected from military personnel during the U.S. Army's investigation of
      a series of cases of acute eosinophilic pneumonitis in military personnel
      deployed in Operation Iraqi Freedom. Eight species of Bacillus, including five
      new species, and one new species of Kurthia were isolated from the cigarettes.
      Some of these species have been identified elsewhere as causes of
      hypersensitivity pneumonitis and other respiratory syndromes. All of the isolates
      were facultative anaerobes, and many displayed mucoid growth under anaerobic
      conditions. In addition, many isolates also displayed the ability to form surface
      biofilms under liquid culture. Although biofilm formation and mucoid growth were
      not correlated, the former was found to be much more pronounced under anaerobic
      conditions as opposed to aerobic ones. The implications of these findings are
      discussed.

PMID- 15942701
TI  - Prevalence of Ile-460-Val/ParE substitution in clinical Streptococcus pneumoniae
      isolates that were less susceptible to fluoroquinolones.
AB  - A total of 73 clinical isolates of Streptococcus pneumoniae were measured for
      susceptibilities to nine fluoroquinolones, and nucleotide sequences of the
      quinolone resistance-determining regions (QRDRs) were determined. MIC90s of
      sparfloxacin, tosufloxacin, grepafloxacin, and gatifloxacin were less than 0.5
      mg/L and the MIC90 of ciprofloxacin was 2 mg/L, although MIC values of some
      isolates to ciprofloxacin were more than 2 mg/L. We found that 60 of 73 isolates
      had only Ile-460-Val/ParE substitution and two isolates had an additional
      substitution of Ser-114-Gly/GyrA, while none of the isolates had any other
      substitutions in QRDRs of either ParC/E or GyrA/B. The isolates carrying Ile-460
      Val/ParE substitution were more resistant to the fluoroquinolones norfloxacin and
      ciprofloxacin than the isolates with no amino acid substitution and the
      differences in MIC values were significant, suggesting that Ile-460-Val/ParE
      substitution in recent clinical S. pneumoniae isolates should be involved in the
      low-level fluoroquinolone resistance.

PMID- 15942702
TI  - Fracture Reduction Affects Medicare Economics (FRAME): impact of increased
      osteoporosis diagnosis and treatment.
AB  - Osteoporosis is a common, debilitating disease affecting US Medicare
      beneficiaries, yet diagnosis and treatment lag behind medical advances. We
      estimated the cost of fractures to the Medicare program and the impact of
      increasing osteoporosis diagnosis and treatment. A Markov model was used to
      predict fracture incidence and costs in postmenopausal women aged 65 years and
      older, over 3 years (2001-2003). Only 1.80 million women were estimated to
      receive a Medicare-reimbursed bone mineral density (BMD) test in 2001. We
      evaluated the budget impact of testing an additional 1 million women from
      Medicare and patient perspectives. These women were stratified into high-risk
      (osteoporotic with prevalent vertebral fracture) and moderate-risk (without
      prevalent vertebral fracture) groups. During 2001-2003, an estimated 2.39 million
      fractures occurred among the 5.11 million women aged 65+ with osteoporosis, at a
      cost to Medicare of 12.96 billion dollars. We projected that BMD testing of an
      additional 1 million women in 2001 would result in treatment of 440,000 new
      patients with a bone-specific medication, preventing over 35,000 fractures over
      the 3 years. The decrease in fractures would produce a net discounted savings to
      the Medicare budget of 77.86 million dollars. Medicare's hospital inpatient cost
      would decrease by 115.41 million dollars and long-term care cost by 43.51 million
      dollars, more than offsetting incremental outpatient cost of 81.07 million
      dollars. Patients would benefit from fracture avoidance, but their out-of-pocket
      medical costs would increase by 63.49 million dollars during 2001-2003, or 1,771
      dollars per fracture avoided. Sensitivity analyses showed that savings to the
      Medicare program varied in proportion to the unit cost of fractures, fracture
      risk of the populations tested, treatment rate, and adherence to therapy.
      Increased osteoporosis diagnosis may produce savings for the Medicare program if
      interventions are targeted to women at elevated risk for fracture and may be
      budget neutral if all older women are screened.

PMID- 15942704
TI  - Diffusion weighted imaging, apparent diffusion coefficient maps and stroke
      etiology.
AB  - OBJECTIVE: In acute ischemic stroke, the number and distribution of lesions on
      diffusion weighted imaging (DWI) have been shown to give clues to the underlying
      pathogenetic mechanisms. The objective of this study was to determine whether
      lesion features on DWI differ between stroke due to large artery atherosclerosis
      (LAA) and cardioembolism (CE), and to assess the role of apparent diffusion
      coefficient maps (ADC). METHODS: We retrospectively studied 83 consecutive
      patients with stroke caused by either LAA (n=40) or cardioembolism (n=43). DWI
      lesions were characterized by number, size, distribution (i. e. lesion pattern)
      and signal intensity on ADC maps. In part A, all hyperintense DWI lesions
      regardless of their ADC were compared. In part B, only hyperintense DWI lesions
      with hypointense appearance on ADC maps (i. e. acute lesions) were assessed.
      RESULTS: Part A: The frequency of multiple hyperintense DWI lesions (LAA: 28/40,
      CE: 21/43; p< 0.05) and the lesion number (LAA 4.7+/- 4.9; CE: 3.1+/- 4.7;
      p=0.01) were higher in LAA-patients. Involvement of >1 circulation (i. e.
      anterior plus posterior or bilateral anterior circulations) was present in 5 LAA
      patients (13 %) and 4 CE-patients (9 %). Lesion size did not differ between LAA
      stroke (35.1+/- 33.7 mm) and CE-stroke (35.4+/- 27.8 mm). Part B: Multiple
      hyperintense DWI lesions with low ADC occurred in 23/40 LAA-patients and in 15/43
      CE-patients (p<0.05). Lesions in >1 circulation occurred only in CE-stroke (n=3;
      7%) and never in LAA-stroke. CONCLUSIONS: (1) Multiple ischemic lesions occur
      significantly more often in LAA-stroke than in CE-stroke. (2) ADC maps are
      important in the comparison of DWI lesion patterns; DWI lesions in >1 circulation
      can only be assigned to a cardioembolic etiology if they appear hypointense on
      ADC maps.

PMID- 15942703
TI  - Inclusion body myositis. Clinical features and clinical course of the disease in
      64 patients.
AB  - The clinical features of inclusion body myositis (IBM) were of minor importance
      in the design of consensus diagnostic criteria, mainly because of controversial
      views on the specificity of signs and symptoms, although some authors reported
      "typical" signs. To re-assess the clinical spectrum of IBM, a single investigator
      using a standard protocol studied a cohort of 64 patients cross-sectionally.
      Symptom onset was before the age of 50 years in 20% of cases. Only a few patients
      (14 %) started with weakness other than that of quadriceps, finger flexor or
      pharyngeal muscles. The sequence of power loss was erratic, but onset of symptoms
      with quadriceps weakness predicted an earlier onset of dysphagia in older
      patients (> or = 56 years) compared with younger ones (< 56 years) (p = 0.02).
      Despite widespread weakness patients had favourable scores on three commonly used
      function scales and they kept their employment. Complete wheel-chair dependency
      was rare (3 %). A dominant characteristic was the anatomical distribution of
      afflicted muscles: ventral extremity muscle groups were more affected than dorsal
      muscle groups and girdle muscles were least affected, the latter preserving
      postural stability. Ankylosis, especially in extension of the fingers,was
      frequently present. Together with the sparing of intrinsic hand muscles it was
      helpful in the preservation of many skillful movements. IBM has a unique
      distribution of muscle weakness. Ankylotic contractures are common. We feel that
      their joint impact on daily functioning is characteristic for the disease.

PMID- 15942706
TI  - Neuropeptide Y and its receptor analogs differentially modulate the
      immunoreactivity for neuronal or endothelial nitric oxide synthase in the rat
      brain following focal ischemia with reperfusion.
AB  - An intracerebroventricular (i.c.v.) injection of neuropeptide Y (NPY) or [Leu31,
      Pro34]-NPY (non-Y2 receptor agonist) given during middle cerebral artery
      occlusion (MCAO) increases the infarct volume and nitric oxide (NO)
      overproduction in the rat brain. An i.c.v. injection of NPY3-36 (non-Y1 receptor
      agonist) has no effects, while BIBP3226 (selective Y1 receptor antagonist)
      reduces the infarct volume and NO overproduction. This study examined the effects
      of NPY or its receptor analog on the immunoreactivity (ir) for three isoforms of
      NO synthase (NOS) following 1 h of MCAO and 3 h of reperfusion. Focal
      ischemia/reperfusion led to increased ir for neuronal NOS (nNOS) within the
      ipsilateral caudate putamen and insular cortex. NPY or [Leu31, Pro34]-NPY
      enhanced but BIBP3226 suppressed such increase in the nNOS-ir. Focal
      ischemia/reperfusion also led to an ipsilateral increase in extent and/or
      intensity of the ir for endothelial NOS (eNOS) in the caudate putamen and/or
      parietal cortex. NPY or [Leu31, Pro34]-NPY suppressed but BIBP3226 enhanced such
      change in the eNOS-ir. NPY3-36 did not consistently influence the nNOS-ir or eNOS
      ir following MCAO. Specific ir for inducible NOS was undetectable. These opposing
      effects of NPY-Y1 receptor activation or inhibition on nNOS and eNOS may lead to
      harmful or beneficial consequences following ischemia/reperfusion.

PMID- 15942707
TI  - Carvedilol prevents cardiac hypertrophy and overexpression of hypoxia-inducible
      factor-1alpha and vascular endothelial growth factor in pressure-overloaded rat
      heart.
AB  - The use of beta-blockers has emerged as a beneficial treatment for cardiac
      hypertrophy. Hypoxia-inducible factor-1alpha (HIF-1alpha) is tightly regulated in
      the ventricular myocardium. However, the expression of HIF-1alpha in cardiac
      hypertrophy due to pressure overload and after treatment with beta-blocker is
      little known. To evaluate the effect of carvedilol on both myocardial HIF-1alpha
      expression and cardiac hypertrophy, infra-renal aortic banding was performed for
      4 weeks in adult Sprague-Dawley rats to induce cardiac hypertrophy. Carvedilol at
      50 mg/kg body weight per day after surgery was given. Heart weight and the ratio
      of heart weight and body weight increased significantly after aortic banding for
      4 weeks in the absence of drug treatment. Mean arterial pressure increased from
      80 +/- 9 mmHg in the sham group to 94 +/-5 mmHg (p < 0.001) in the banding group.
      Echocardiography showed concentric hypertrophy after aortic banding. Mean
      arterial pressure decreased after treatment with carvedilol. The increased wall
      thickness and heart weight was reversed to normal by carvedilol. Western blot
      showed that HIF-1alpha, vascular endothelial growth factor (VEGF) and brain
      natriuretic peptide (BNP) proteins were up-regulated and nerve growth factor-beta
      (NGF-beta) down-regulated in the banding group. Treatment with valsartan,
      doxazosin, or N-acetylcysteine did not significantly affect HIF-1alpha and VEGF
      proteins expression in the banding groups. Real-time polymerase chain reaction
      showed that mRNA of HIF-1alpha, VEGF and BNP increased and mRNA of NGF-beta
      decreased in the banding group. Treatment with carvedilol reversed both protein
      and mRNA of HIF-1alpha, VEGF, BNP, and NGF-beta to the baseline values. Increased
      immunohistochemical labeling of HIF-1alpha, VEGF, and BNP in the ventricular
      myocardium was observed in the banding group and carvedilol again normalized the
      labeling. In conclusion, HIF-1alpha, VEGF, and BNP mRNA and protein expression
      were up-regulated, while NGF-beta mRNA and protein was downregulated in the rat
      model of pressure-overloaded cardiac hypertrophy. Treatment with carvedilol is
      associated with a reversal of abnormal regulation of HIF-1alpha, VEGF, BNP, and
      NGF-beta in the hypertrophic myocardium.

PMID- 15942708
TI  - Regular arrangement of collecting venules (RAC): a characteristic endoscopic
      feature of Helicobacter pylori-negative normal stomach and its relationship with
      esophago-gastric adenocarcinoma.

PMID- 15942709
TI  - Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is
      more suitable for on-demand use?
AB  - BACKGROUND: Medication for the relief of heartburn should have the rapid onset of
      action required for on-demand use. We studied the inhibition of gastric acid
      secretion by lafutidine and rabeprazole, given in single doses to fasting and
      postprandial subjects. METHODS: A total of 22 healthy male, Helicobacter pylori
      negative volunteers participated in this randomized, two-way crossover study.
      They were randomly assigned to receive a single oral dose of 10 mg lafutidine or
      20 mg rabeprazole after fasting overnight (12 subjects, fasting study) or after
      eating a test meal (noodles, 364 kcal; protein, 10.1 g; fat, 16 g; carbohydrates,
      44.9 g; NaCl, 1.1 g; 10 subjects, postprandial study). Intragastric pH was
      monitored continuously for 6 h after treatment. The other drug was given after a
      washout period of at least 7 days, and intragastric pH was similarly monitored.
      RESULTS: In the fasting study, lafutidine sustained pH at >3 and >4 during the
      second, third, fourth, fifth, and sixth hours of the study for significantly
      longer than rabeprazole. During the first 6 h after treatment, lafutidine
      sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In
      the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than
      rabeprazole during the third, fourth, fifth, and sixth hours of the study. During
      the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4,
      5, 6, and 7 longer than rabeprazole. CONCLUSIONS: Lafutidine 10 mg produces a
      prompter rise in intragastric pH than rabeprazole 20 mg in fasting and
      postprandial Helicobacter pylori-negative male subjects.

PMID- 15942710
TI  - Suppressive effect of rice extract on Helicobacter pylori infection in a
      Mongolian gerbil model.
AB  - BACKGROUND: Rice extract has been shown to protect gastric mucosa from stress
      induced damage. In this study, the antibiotic effect and the anti-inflammatory
      effect of orally administered aqueous rice extract on Helicobacter pylori
      infection and H. pylori-induced gastritis, respectively, in Mongolian gerbils
      were investigated. METHODS: Fifty specific-pathogen-free male Mongolian gerbils,
      seven weeks old, were divided into four groups: uninfected, untreated animals
      (group A); uninfected, rice extract-treated animals (group B); H. pylori
      infected, untreated animals (group C); and H. pylori-infected, rice extract
      treated animals (group D). Group C and D animals were killed 12 weeks after H.
      pylori infection (i.e., at 19 weeks of age) and group A and B animals were also
      killed at age 19 weeks. The stomachs were removed for histopathological
      examination with hematoxylin-and-eosin staining and anti-5'-bromo-2'-deoxyuridine
      (BrdU) immunostaining, and to determine the bacterial burden. Serum anti-H.
      pylori antibody titers were also tested. RESULTS: In groups A and B, the gastric
      mucosa showed no inflammatory cell infiltration and a few BrdU-reactive cells.
      Group C animals developed marked chronic active gastritis in the gastric mucosa,
      and BrdU-labeled cells in the gastric mucosa markedly increased in number. In
      group D animals, a significant reduction occurred in the degree of neutrophilic
      polymorphonuclear cell infiltration into the gastric mucosa, in the BrdU-labeling
      indices of gastric epithelial cells, and in anti-H. pylori antibody titers in the
      serum (P < 0.01), compared with although H. pylori was not completely eradicated.
      CONCLUSIONS: The rice extract was effective in suppressing inflammation and
      epithelial cell proliferation in the gastric mucosa in H. pylori-infected
      Mongolian gerbils. The rice extract has potential to exhibit a protective effect
      on H. pylori-related gastric mucosal diseases.

PMID- 15942711
TI  - A study of histopathological assessment criteria for assessing malignancy of
      gastrointestinal stromal tumor, from a clinical standpoint.
AB  - BACKGROUND: As no established histopathological criteria exist for assessing the
      malignant potential of gastrointestinal stromal tumor (GIST), recurrence or
      metastasis is occasionally observed in lesions diagnosed histopathologically as
      benign. The present study aimed to clarify the histopathological criteria for
      assessing the malignancy of GIST, from a clinical standpoint. METHODS: The
      subjects were 22 patients with GIST expressing CD117 (c-kit) and/or CD34, who
      were followed up for more than 2 years. Clinically, GIST malignancy was diagnosed
      if any of the following criteria were met: peripheral invasive growth, lymph node
      metastasis, metastasis to another organ, peritoneal dissemination, recurrence, or
      death. GIST was also categorized as either benign or malignant by a new
      histological malignancy classification system, based on the determination of
      significant factors indicating malignancy in the clinical classification system
      above. RESULTS: Significant factors for malignancy identified in the clinical
      malignancy classification were: tumor hemorrhage/necrosis (present vs absent; P =
      0.0053), tumor size (<5 cm vs > or =5 cm; P = 0.0022), and Ki-67 labeling index
      (<3% vs > or =3%; P = 0.0002). A new histological malignancy classification,
      based on a combination of these three factors, was developed. A significant
      correlation existed between the clinical system and the new histological
      malignancy classification system (P = 0.0008). The recurrence-free survival rate
      was 100% in the histologically benign cases and 37.5% in the histologically
      malignant cases (P = 0.0012). CONCLUSIONS: The new histological malignancy
      classification for GIST was demonstrated to be useful from a clinical standpoint.

PMID- 15942712
TI  - Ecabet sodium prevents the delay of wound repair in intestinal epithelial cells
      induced by hydrogen peroxide.
AB  - BACKGROUND: Recent studies showed that ecabet sodium (ES), a gastro-protective
      agent, also had a therapeutic effect on inflammation in ulcerative colitis. The
      aim of this study was to clarify the function of ES in wound repair in intestinal
      epithelial cells (IECs). METHODS: The activation of signal proteins (ERK1/2
      mitogen-activated protein kinase MAPK, and IkappaB-alpha) in IEC-6 cells after
      stimulation with 2.5 mg/ml of ES was assessed by Western blot. The induction of
      transforming growth factor (TGF)-beta1, TGF-alpha, and cyclooxygenase-2 (COX-2)
      mRNAs after the stimulation of IEC-6 cells with ES was assessed by reverse
      transcription ploymerase chain reaction (RT-PCR). IEC-6 cells were wounded and
      cultured for 24 h with various concentrations of ES in the absence or presence of
      20 microM H2O2. Epithelial migration or proliferation was assessed by counting
      migrated or bromodeoxyuridine (BrdU)-positive cells observed across the wound
      border. We also assessed apoptotic epithelial cells after the culture. RESULTS:
      ES clearly activated ERK1/2 MAPK and slightly activated IkappaB-alpha. ES also
      enhanced the expression of TGF-alpha and COX-2 mRNAs. This enhancement was
      suppressed by a MAPK/Erk kinase (MEK) inhibitor. ES did not enhance epithelial
      migration in the absence of H2O2. In contrast, ES significantly decreased the
      number of apoptotic cells and prevented the reduction of epithelial migration
      (51.1%; P < 0.01) and proliferation (56%; P < 0.01) induced by H2O2. The function
      of ES was suppressed by a cyclooxygenase-2 (COX-2) inhibitor and by the MEK
      inhibitor, and partly suppressed by a nuclear factor (NF)-kappaB inhibitor.
      CONCLUSIONS: ES prevents the delay of wound repair in IEC-6 cells induced by
      H2O2, probably through the activation of ERK1/2 MAPK and the induction of COX-2.

PMID- 15942713
TI  - Butyrate blocks interferon-gamma-inducible protein-10 release in human intestinal
      subepithelial myofibroblasts.
AB  - BACKGROUND: Interferon (IFN)-gamma-inducible protein (IP)-10 is a chemoattractant
      for CXCR 3-expressing T lymphocytes and monocytes. IP-10 has been reported to
      mediate chronic inflammation such as that in inflammatory bowel disease (IBD).
      However, the local secretion of IP-10 in the intestine remains unclear. In this
      study, we investigated IP-10 secretion in human colonic subepithelial
      myofibroblasts (SEMFs). METHODS: IP-10 secretion was determined by enzyme-linked
      immunosorbent assay (ELISA), and IP-10 mRNA expression was evaluated by Northern
      blotting. RESULTS: Interleukin (IL)-10 mRNA was not detected in unstimulated
      SEMFs. Interferon (IFN)-gamma strongly induced IP-10 mRNA expression. Tumor
      necrosis factor (TNF)-alpha also stimulated IP-10 mRNA expression, but this was
      much weaker than that induced by IFN-gamma. The effects of IFN-gamma and TNF
      alpha were detected in a dose- and time-dependent manner. These responses were
      also observed at the protein levels. The IFN-gamma-induced IP-10 secretion was
      not affected by acetate or propionate, but was significantly reduced by butyrate.
      Trichostatin A, a specific inhibitor of histone deacetylase, also blocked the IFN
      gamma- and TNF-alpha-induced IP-10 mRNA expression, but the effects of
      trichostatin A were weaker than those of butyrate. The inhibitory effect of
      butyrate on IFN-gamma-induced IP-10 release was not associated with STAT
      (signaling transducer and activator of transcription)-1alpha activation.
      CONCLUSIONS: We demonstrated that human colonic SEMFs are the local site for the
      secretion IP-10. The regulation of IP-10 release by IFN-gamma and butyrate may
      play an important role in controlling chronic mucosal inflammation in
      pathological entities such as IBD.

PMID- 15942714
TI  - Apoptosis and inhibition of the phosphatidylinositol 3-kinase/Akt signaling
      pathway in the anti-proliferative actions of dehydroepiandrosterone.
AB  - BACKGROUND: Dehydroepiandrosterone (DHEA) is an endogenous steroid that is
      synthesized mainly in the adrenal cortex; it is found in plasma as the sulfate
      conjugated form (DHEA-S). Pharmacological doses of DHEA exhibit anti
      proliferative effects on malignant cell lines and some tumors in experimental
      animals. The purpose of this study was to evaluate the effect of these steroids
      on proliferation in human cancer cell lines. METHODS: HepG2 and HT-29 cell lines
      were treated with DHEA or DHEA-S at 0-200 microM for 24 h or at 100 microM for 8
      72 h, and then effects on cell growth, and the cell cycle and on apoptosis, were
      evaluated by 3-[4,5-dimethylthiazol]-2yl-2,5-diphenyl tetrazolium bromide (MTT)
      assay and flow cytometry, respectively. Also, the effect of DHEA on
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling was investigated in HepG2
      cells by Western blotting. RESULTS: The growth of HepG2 and HT-29 cells was
      significantly inhibited by DHEA, in a dose- and time-dependent manner. This
      inhibition was greater in HepG2 than in HT-29 cells. Accumulation at G0/G1 phase
      in both cell lines was observed with DHEA treatment. However, apoptosis increased
      significantly only in HepG2 cells. In contrast, DHEA-S exhibited much weaker
      growth inhibitory and cytostatic effects on both cell lines, and apoptosis was
      not detected. In HepG2 cells treated with DHEA, apoptosis was associated with
      markedly reduced Akt phosphorylation (Thr308 and Ser473), suggesting that DHEA
      inhibited the PI3K/Akt signaling to induce apoptosis in these cells. CONCLUSIONS:
      These results suggest that the induction of apoptosis through the inhibition of
      the PI3K/Akt signaling pathway is one of the anti-proliferative mechanisms of
      DHEA in certain tumors, but that DHEA also promotes cell-cycle arrest without the
      induction of apoptosis.

PMID- 15942715
TI  - Enhancement of EFS-induced contractions, by agmatine, in guinea pig gallbladder
      smooth muscle strips.
AB  - BACKGROUND: Electrical field stimulation of gallbladder muscle strips produces
      frequency-dependent contractions by activating cholinergic nerves. The
      cholinergic motor function of the gallbladder and enteric system is also
      modulated by other mediators. The aim of this study was to investigate the role
      of agmatine, a ligand for alpha 2-adrenoceptors and imidazoline binding sites, in
      the cholinergic motor activity of guinea pig gallbladder smooth muscle. METHODS:
      Gallbladder muscle strips obtained from guinea pigs were subjected to electrical
      field stimulation (1-64 Hz, 100 V, 1-ms pulse width, and 10-s train duration).
      Frequency-response contractions of gallbladder muscle strips were traced before
      and after the addition of cumulative concentrations of agmatine (10(-5)-10(-3) M)
      to the tissue bath. The same set of experiments was repeated in the presence of
      different antagonists. RESULTS: Agmatine by itself did not produce any
      contractions in guinea pig gallbladder muscle strips, but significantly enhanced
      the contractile response produced by electrical field stimulation. Yohimbine (10(
      6) M), a selective alpha 2-adrenergic blocker, neither decreased nor increased
      the enhancement induced by agmatine. However, idazoxan (10(-4) M), an alpha
      receptor blocker and imidazoline receptor antagonist, abolished this enhanced
      contractile response. Pretreatment with N(W)-nitro L-arginine methyl ester (L
      NAME; 30 microM), and indomethacin (10 microM) did not inhibit the effect of
      agmatine. CONCLUSIONS: Our findings indicate that agmatine has a modulator role
      in the electrical field stimulation-induced cholinergic contractions of guinea
      pig gallbladder smooth muscle strips, and this role could be mediated by
      imidazoline receptors. Receptor binding studies should be done to determine the
      presence of endogenous agmatine and imidazoline receptors in gallbladder smooth
      muscle.

PMID- 15942716
TI  - Upregulation of BNIP3 by 5-aza-2'-deoxycytidine sensitizes pancreatic cancer
      cells to hypoxia-mediated cell death.
AB  - BACKGROUND: Pancreatic cancer cells often show resistance to hypoxia-mediated
      apoptosis, but the molecular mechanism underlying that resistance remains
      unknown. The purpose of the present study, therefore, was to examine the role of
      epigenetic gene alteration in the resistance to hypoxia-mediated apoptosis among
      pancreatic cancer cells. METHODS: Reverse transcription-polymerase chain reaction
      (RT-PCR) was used to examine the expression of five genes associated with hypoxia
      mediated apoptosis (PUMA, Caspase-8 [CASP8], APAF-1, BNIP3, and BNIP3L) in a
      panel of pancreatic cancer cell lines. Protein expression was examined by Western
      blot analysis, using lysates from cells incubated under normoxic or hypoxic
      conditions. The methylation status of the genes was determined using bisulfite
      PCR and sequencing. The percentages of cells that were apoptotic were determined
      using flow cytometry. RESULTS: Under normoxic conditions, the expression of the
      BNIP3 gene varied among the 12 pancreatic cancer cell lines tested, with 50% of
      them showing no BNIP3 expression at all, whereas expression of the other four
      genes was readily detected in all 12 cell lines. DNA methylation of BNIP3's CpG
      island in the region around the transcription start site of the gene was closely
      associated with its silencing. The expression of BNIP3 was restored by the
      methyltransferase inhibitor 5-aza-deoxycytidine (5-aza-dC), as was the hypoxia
      mediated pancreatic cancer cell death. CONCLUSIONS: BNIP3 expression is silenced
      in some pancreatic cancer cells by the methylation of its CpG island.
      Demethylation of BNIP3, using a methyltransferase inhibitor, restores the gene's
      expression and induces hypoxia-mediated cell death. BNIP3 may thus be a useful
      target for new therapies aimed at treating pancreatic cancer.

PMID- 15942717
TI  - Comparative genomic hybridization analysis for pancreatic cancer specimens
      obtained by endoscopic ultrasonography-guided fine-needle aspiration.
AB  - BACKGROUND: Comparative genomic hybridization (CGH) analysis of pancreatic cancer
      has been done exclusively for surgical and autopsy specimens, because of the
      difficulty of tissue sampling without surgery. To overcome this difficulty, we
      applied CGH technology to cells obtained by endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). METHODS: In the present study, we performed EUS-FNA
      for 17 patients with pancreatic cancer before surgery. Tumor cells were selected
      by microdissection. DNA was extracted from the cells and amplified by degenerate
      oligonucleotide-primed polymerase chain reaction (DOP-PCR). Then CGH was carried
      out. RESULTS: In the 15 patients with tubular adenocarcinoma, the most common
      loci of gains (including amplification) were 5p, 8q, and 20q (60% of the
      patients); and 1q, 7p, and 12p (27%). The most frequent losses were 17p (73%);
      9p, 18q, and 19p (47%); and 8p (33%). These findings were similar to our
      previously reported data. Both of the patients with acinar cell carcinoma showed
      gains of 2q and 5p, and losses of 1p, 9p, 9q, 11p, 11q, 14q, 17p, 17q, and 18q.
      CONCLUSIONS: The results of this study suggest that comprehensive genetic
      analysis is possible for EUS-FNA biopsy specimens, with a combination of
      microdissection and DOP-PCR. This analytical strategy will enable us to evaluate
      the biological characteristics of pancreatic cancer before treatment.

PMID- 15942718
TI  - Differential diagnosis of pancreatic tumors using ultrasound contrast imaging.
AB  - BACKGROUND: The development of equipment and contrast agents for ultrasound
      imaging has contributed to major breakthroughs in the diagnosis of pancreatic
      tumors. We aimed to determine the diagnostic effectiveness of contrast ultrasound
      with Levovist, using the Agent Detection Imaging (ADI) technique, in 50 patients
      with pancreatic tumors. METHODS: We studied 50 cases of histologically proven
      pancreatic disease; 39 carcinomas, 2 endocrine tumors, 4 intraductal papillary
      mucinous carcinomas (IPMCs), and 5 cases of tumor-forming pancreatitis (TFP).
      Vascular and perfusion images of contrast-enhanced ultrasound (CE-US) were used
      for the evaluation of tumor vascularity and parenchymal perfusion of the tumor,
      respectively. The hemodynamics of the tumor, and the diagnostic capacity of CE-US
      were compared with those shown by computed tomography (CT). The histological
      diagnosis in all cases was made from either biopsy or surgical specimens.
      RESULTS: Thirty-four cases of pancreatic carcinoma (87%) showed a hypovascular
      and hypoperfusion pattern. The endocrine tumors showed a heterogeneous
      hypervascular and hyperperfusion pattern. All IPMC cases showed hypervascularity
      of the nodules inside the tumors. TFP showed an isovascular and homogeneous
      isoperfusion pattern. When tumors showing a hypovascular or hypoperfusion pattern
      on CE-US were diagnosed as carcinomas, 34 of the 39 carcinomas (87%) fit this
      criterion, with a 95% confidence interval (CI) of 73%-96%, whereas, on CT, 31 of
      the 39 were diagnosed as carcinoma; (sensitivity, 79%). The sensitivity and
      accuracy of CT were inferior to those of CE-US. Results of comparison between the
      CE-US findings and the histological diagnosis were as follows. The one papillary
      adenocarcinoma showed a hypervascular and hyperperfusion pattern; the 32 well or
      moderately differentiated adenocarcinomas showed a hypovascular and hypoperfusion
      pattern; and in the poorly differentiated adenocarcinomas, 2 cases of scirrhous
      type showed a hypovascular and hypoperfusion pattern, and the 4 cases of
      medullary type showed an isovascular and isoperfusion pattern. CONCLUSIONS: The
      differences in vascularity of pancreatic carcinomas depicted by CE-US were
      associated well with differences in histology. CE-US, by the ADI technique, is
      useful for the diagnosis of pancreatic tumors.

PMID- 15942719
TI  - Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in
      mice.
AB  - BACKGROUND: D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury
      is an experimental model of fulminant hepatic failure in which tumor necrosis
      factor-alpha (TNF-alpha) plays a pivotal role. We examined the effects of a
      highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced
      fulminant hepatic failure. METHODS: Mice were given an intraperitoneal dose of
      GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e
      (0.01 microg/kg) treatment. Liver injury was assessed biochemically and
      histologically. Also, TNF-alpha levels in the serum were determined. RESULTS: The
      serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 +/- 2800 IU/ml
      and was reduced by 63% to 7800 +/- 1670 IU/ml by treatment with 0.01 microg/kg
      per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum
      TNF-alpha and greatly reduced inflammation assessed by histopathologic
      examination compared with control mice treated with GalN/LPS. ATL-146e also
      reduced lethality at 12 h from 65% to 13%. CONCLUSION: The present findings
      suggest that the highly selective adenosine A2A receptor agonist (ATL-146e)
      prevents endotoxin-induced lethal liver injury by suppression of TNF-alpha
      secretion.

PMID- 15942720
TI  - Pyogenic granuloma of the stomach successfully treated by endoscopic resection
      after transarterial embolization of the feeding artery.
AB  - Pyogenic granulomas represent the aquisition of vasodilative granulation tissue
      in the skin or mucosa. They are extremely rare in the alimentary tract, other
      than in the oral cavity. Here, we report a case of pyogenic granuloma arising
      from the gastric mucosa. An 82-year-old man was admitted to our hospital because
      of melena of more than 3 months, duration. Esophagogastroduodenoscopy (EGD)
      revealed a 30-mm-diameter semipedunculated lesion with an irregular surface in
      the fundus of the stomach. During hospitalization, the patient's anemia worsened
      due to loss of blood from the lesion, with the level of hemoglobin declining to 6
      g/dl, and a blood transfusion was required. Because radiological and endoscopic
      findings indicated the lesion was hypervascular, transarterial embolization of
      the nutritional artery of the lesion was performed before endoscopic resection of
      the lesion. One week after the embolotherapy, endoscopic mucosal resection was
      performed, without any complications, such as massive bleeding. Histological
      studies of the resected specimen revealed many capillaries of various sizes,
      lined with plump endothelial cells, and accompanied by acute and chronic
      inflammatory infiltrates. On the basis of these observations, the lesion was
      diagnosed as a pyogenic granuloma. One year later, the patient was asymptomatic
      and there was no evidence of tumor recurrence on follow-up EGD.

PMID- 15942721
TI  - Colonic obstruction due to giant inflammatory polyposis in a patient with
      ulcerative colitis.
AB  - A 32-year-old Japanese woman with a 14-month history of ulcerative colitis (UC),
      pancolitis type, was referred to our institution, because of abdominal
      distention. Plain abdominal X-ray and computed tomography (CT) showed marked
      dilatation of the right side of the colon. The patient was treated by immediate
      total colectomy, with the diagnosis of toxic megacolon. Macroscopically, there
      was a constricting lesion with giant polyposis in the middle part of the
      transverse colon. Histologically, there was transmural inflammation with a
      thickened proper muscular layer overlaid by inflammatory polyposis. This case
      suggests that giant polyposis in UC patients may result in severe stenosis and
      that such a condition should not be misinterpreted as toxic megacolon or as
      colitic cancer.

PMID- 15942722
TI  - Biliary hamartomas with delayed 99mTc-diisopropyl iminodiacetic acid clearance.
AB  - We report a 61-year-old asymptomatic man who had a hepatic lesion whose nature
      was undetermined, based on biochemistry, serology, ultrasonography, computed
      tomography, and magnetic resonance imaging studies. Biliary hamartomas were
      diagnosed by echo-guided needle biopsy. Functional studies of bile excretion,
      using 99mTc-diisopropyl iminodiacetic acid (99mTc-DISIDA) scintigraphy liver
      single-photon emission computed tomography (SPECT) showed the delayed transit of
      tracers from hepatocytes to the biliary hamartomas and the delayed emptying of
      tracers to the neighboring bile ducts. Therefore, biliary hamartomas should be
      included in the differential diagnosis of single or multiple hepatic lesions
      whose nature is undetermined, and a liver biopsy would be warranted for further
      treatment plans. We believe this is the first functional study of bile excretion
      in biliary hamartomas using radionucleotide studies; such studies may have
      prognostic implications.

PMID- 15942723
TI  - Primary malignant melanoma of the esophagus treated by esophagectomy and adjuvant
      dendritic-cell therapy.

PMID- 15942724
TI  - Long-term fibrate treatment for PBC.

PMID- 15942725
TI  - Rupture of peritoneal metastatic tumor that developed due to needle-tract
      implantation of hepatocellular carcinoma.

PMID- 15942726
TI  - A new-generation H2 receptor antagonist: quicker and stronger acid inhibition
      than proton pump inhibitors in the clinical setting?

PMID- 15942727
TI  - IP10 released by colonic subepithelial myofibroblasts: by which stimuli and for
      which tissue?

PMID- 15942728
TI  - The role of dehydroepiandrosterone in apoptosis and proliferation and its
      relation to the phosphatidyl inositol-3-kinase/Akt signaling pathway.

PMID- 15942729
TI  - NO binding to naphthalene dioxygenase.
AB  - Nitric oxide (NO) is commonly used as an analogue for dioxygen in structural and
      spectroscopic studies of oxygen binding and oxygen activation. In this study,
      crystallographic structures of naphthalene dioxygenase (NDO) in complex with
      nitric oxide are reported. In the presence of the aromatic substrate indole, NO
      is bound end-on to the active-site mononuclear iron of NDO. The structural
      observations correlate well with spectroscopic measurements of NO binding to NDO
      in solution. However, the end-on binding of NO is in contrast to the recently
      reported structure of oxygen to the active-site iron of NDO that binds side-on.
      While NO is a good oxygen analogue with many similarities to O(2), the different
      binding mode of NO to the active-site iron atom leads to different mechanistic
      implications. Hence, caution needs to be used in extrapolating NO as an analogue
      to O(2) binding.

PMID- 15942730
TI  - [PACS: storage and retrieval of digital radiological image data].
AB  - BACKGROUND: Efficient handling of both picture archiving and retrieval is a
      crucial factor when new PACS installations as well as technical upgrades are
      planned. MATERIALS AND METHODS: For a large PACS installation for 200 actual
      studies, the number, modality,and body region of available priors were evaluated.
      In addition, image access time of 100 CT studies from hard disk (RAID), magneto
      optic disk (MOD), and tape archives (TAPE) were accessed. RESULTS: For current
      examinations priors existed in 61.1% with an averaged quantity of 7.7 studies.
      Thereof 56.3% were within 0-3 months, 84.9% within 12 months, 91.7% within 24
      months, and 96.2% within 36 months. On average, access to images from the hard
      disk cache was more than 100 times faster then from MOD or TAPE. CONCLUSION:
      Since only PACS RAID provides online image access, at least current imaging of
      the past 12 months should be available from cache. An accurate prefetching
      mechanism facilitates effective use of the expensive online cache area. For that,
      however, close interaction of PACS, RIS, and KIS is an indispensable
      prerequisite.

PMID- 15942731
TI  - Use of guiding sheaths in peroral fluoroscopic gastroduodenal stent placement.
AB  - Our purpose was to assess the safety and usefulness of guiding sheaths in peroral
      fluoroscopic gastroduodenal stent placement. Two types of guiding sheath were
      made from straight polytetrafluoroethylene tubes. Type A was 80 cm in length, 4
      mm in outer diameter and 3 mm in inner diameter. Type B was 70 cm in length, 6 mm
      in outer diameter and 5 mm in inner diameter. The type A sheath was used in 18
      patients in whom a catheter-guide wire combination failed to pass through a
      stricture. The type B sheath was used in 22 patients in whom a stent delivery
      system failed to pass through the stricture due to loop formation within the
      gastric lumen. The overall success rate for guiding a catheter-guide wire through
      a stricture after using the type A sheath was 89%. The overall success rate for
      passing a stent delivery system through a stricture after using the type B sheath
      was 100%. All procedures were tolerated by the patients without any significant
      complications. The guiding sheaths were safe and useful in peroral fluoroscopic
      gastroduodenal stent placement.

PMID- 15942732
TI  - Complementary role of helical CT cholangiography to MR cholangiography in the
      evaluation of biliary function and kinetics.
AB  - To explore the potential role of computed tomographic cholangiography (CTC) in
      relation to magnetic resonance cholangiography (MRC) in cases in which knowledge
      of biliary kinetics and functional information are important for therapeutic
      decisions, 31 patients (14 men and 17 women) underwent MRC followed by CTC. We
      examined nine post-cholecystectomy cases with right upper quadrant abdominal
      pain, six cases with a previous biliary-enteric anastomosis and clinical evidence
      of cholangitis, eight biliary strictures with pain or symptoms of cholangitis,
      four cases with strong clinical evidence of sclerosing cholangitis, three cases
      with suspected post-laparoscopic cholecystectomy bile leakage, and one case with
      chronic pancreatitis and a common bile duct stent associated with cholangitis. In
      relation to MRC, CTC provided additional biliary functional information as
      follows: abnormal biliary drainage through the ampulla in 7/9 cholecystectomy
      cases, impaired drainage in 3/6 biliary-enteric anastomoses, and complete
      obstruction in 2/8 biliary strictures. CTC diagnosed early sclerosing cholangitis
      in 4/4 cases and confirmed suspected bile leakage in 1/3 post-laparoscopic
      cholecystectomy patients, and the patency of the biliary stent in the patient
      with chronic pancreatitis. Thus, CTC provides clinically important information
      about the function and kinetics of bile and complements findings obtained by MRC.

PMID- 15942733
TI  - Bowel magnetic resonance imaging of pediatric patients with oral mannitol MRI
      compared to endoscopy and intestinal ultrasound.
AB  - The purpose of this study was to assess the sensitivity, specificity, and
      diagnostic accuracy of magnetic resonance imaging (MRI) in pediatric patients
      with clinical suspicion of inflammatory bowel disease (IBD) by comparing MRI and
      ultrasound (US) to endoscopy, the gold standard. A median volume of 300 ml of
      mannitol in a 15% [corrected] watery solution were ingested by 43 children prior
      to examination. The 53 MRI examinations were compared with 20 endoscopies and 41
      US of the terminal ileum. The outcomes were MRI quality; pathologic findings;
      level of adverse events; and concordance between endoscopy, MRI, and US estimated
      by kappa statistics. The ileum and terminal ileum were very good or excellently
      imaged in approximately 80% of cases. Wall thickening and enhancement were most
      frequent in the terminal ileum. MRI compared with endoscopy had a sensitivity of
      81.8% [95% confidence interval (CI)], specificity of 100%, diagnostic accuracy of
      90%, and kappa value of 0.80 (95% CI), indicating a good degree of concordance. A
      similar degree of concordance was achieved between US and endoscopy. In spite of
      the frequent adverse reactions, such as diarrhea and nausea, half of the patients
      were prepared to repeat the examination. The results of MRI are concordant with
      endoscopy and US of the terminal ileum.

PMID- 15942734
TI  - Startle-induced reaction time shortening is not modified by prepulse inhibition.
AB  - A startling auditory stimulus delivered during preparation for execution of a
      ballistic movement in a simple reaction time task experiment induces two effects:
      a startle response and a reaction time shortening (the StartReact effect). We
      investigated whether prepulse inhibition of the startle response is effective in
      suppressing either one of these effects during motor preparation. Twelve healthy
      volunteers were presented with seven different experimental conditions in random
      order: while at rest, subjects received a low intensity electrical shock on the
      middle finger of the left hand (Prep), a loud auditory stimulus (Start), or a
      combination of these two (PrepStart). While engaged in preparation for a visual
      simple reaction time task, they were presented with the imperative signal for
      execution of the reaction (React), or with any of the combinations PrepReact,
      StartReact, or PrepStartReact. We recorded the EMG activity from the orbicularis
      oculi and the sternocleidomastoid muscles to assess the startle response, and
      from the wrist extensor muscles to assess reaction time. The startle response was
      markedly reduced when Prep was presented 100 ms before Start regardless of
      whether the subjects were at rest or preparing for the reaction. Reaction time
      shortened significantly in StartReact trials with respect to React trials, and
      the percentage shortening was not different in trials in which Prep preceded
      StartReact and inhibited the startle response. The fact that prepulse inhibition
      of the startle response is not accompanied by modification of the StartReact
      effect indicates that there are separate physiological mechanisms for the two
      effects, an observation that has implications for further understanding of the
      processes underlying motor preparation for a ballistic reaction.

PMID- 15942735
TI  - Spatiotemporal interactions between audition and touch depend on hand posture.
AB  - We report two experiments designed to assess the consequences of posture change
      on audiotactile spatiotemporal interactions. In Experiment 1, participants had to
      discriminate the direction of an auditory stream (consisting of the sequential
      presentation of two tones from different spatial positions) while attempting to
      ignore a task-irrelevant tactile stream (consisting of the sequential
      presentation of two vibrations, one to each of the participant's hands). The
      tactile stream presented to the participants' hands was either spatiotemporally
      congruent or incongruent with respect to the sounds. A significant decrease in
      performance in incongruent trials compared with congruent trials was demonstrated
      when the participants adopted an uncrossed-hands posture but not when their hands
      were crossed over the midline. In Experiment 2, we investigated the ability of
      participants to discriminate the direction of two sequentially presented tactile
      stimuli (one presented to each hand) as a function of the presence of congruent
      vs incongruent auditory distractors. Here, the crossmodal effect was stronger in
      the crossed-hands posture than in the uncrossed-hands posture. These results
      demonstrate the reciprocal nature of audiotactile interactions in spatiotemporal
      processing, and highlight the important role played by body posture in modulating
      such crossmodal interactions.

PMID- 15942736
TI  - Gustatory coding in the precentral extension of area 3 in Japanese macaque
      monkeys; comparison with area G.
AB  - The precentral extension of area 3 as well as the transition between the frontal
      operculum and insula (area G) comprises the primary gustatory cortex in the
      subhuman primate, receiving projections from the thalamic taste relay. However,
      in contrast to the extensive studies that have been carried out on the latter
      area, only a few taste units in the former area have been recorded. To clarify
      gustatory coding in area 3, we investigated the taste response properties of
      neurons in area 3 compared with those in area G in alert monkeys by infiltrating
      into their mouths seven taste stimuli [0.3 M sucrose (S), 0.1 M NaCl (N), 0.01 N
      HCl (H), 0.003 M quinine-HCl (Q), 0.1 M monosodium glutamate (MSG), distilled
      water (W), and orange juice (OR)] and artificial saliva (SA). A larger number of
      HCl-best units and a smaller number of quinine-best units were found in area 3
      than in area G. The onset latency and response duration were significantly
      shorter in area 3 than in area G. Weighted multi-dimensional scaling showed that
      area G divided eight stimulants into four classes, i.e. two groups (H-Q-W and S
      MSG-OR), N and SA, whereas area 3 divided them into three classes (N-MSG-W-OR, S
      Q, and H-SA). This suggested that tastants not separated in area G were separated
      in area 3, and vice versa. This indicates that both areas complement each other
      in the representation of taste stimuli, each contributing to taste information
      processing in a different manner.

PMID- 15942737
TI  - Rapid adaptation of torso pointing movements to perturbations of the base of
      support.
AB  - We investigated whether pointing movements made with the torso would adapt to
      movement-contingent augmentation or attenuation of their spatial amplitude. The
      pointing task required subjects standing on a platform in the dark to orient the
      mid-sagittal plane of their torso to the remembered locations of just
      extinguished platform-fixed visual targets without moving their feet. Subjects
      alternated pointing at two chest-high targets, 60 degrees apart, (1) in a
      baseline period with the stance platform stationary, (2) during exposure to
      concomitant contra or ipsiversive platform rotations that grew incrementally to
      50% of the velocity of torso rotation, and (3) after return in one step to
      stationary platform conditions. The velocity and amplitude of torso movements
      relative to space decreased 25-50% during exposure to contraversive platform
      rotations and increased 20-50% during ipsiversive rotations. Torso rotation
      kinematics relative to the platform (as well as the platform-fixed targets and
      feet) remained virtually constant throughout the incremental exposure period.
      Subjects were unaware of the altered motion of their body in space imposed by the
      platform and did not perceive their motor adjustments. Upon return to stationary
      conditions, torso rotation movements were smaller and slower following adaptation
      to contraversive rotations and larger and faster after ipsiversive platform
      rotations. These results indicate a rapid sensory-motor recalibration to the
      altered relationship between spatial (inertial) torso motion and intended torso
      motion relative to the feet, and rapid re-adaptation to normal conditions. The
      adaptive system producing such robust torso regulation provides a critical basis
      for control of arm, head, and eye movements.

PMID- 15942738
TI  - Microstimulation of V1 affects the detection of visual targets: manipulation of
      target contrast.
AB  - Electrical microstimulation of the striate cortex (area V1) in monkeys delays the
      execution of saccadic eye movements generated to a visual target located in the
      receptive field of the stimulated neurons. We have argued that this effect is
      because of disruption of the visual signal transmitted along the geniculostriate
      pathway. The delivery of electrical stimulation to V1 evokes a punctate light or
      dark phosphene in human subjects. If electrical stimulation of V1 in monkeys
      evokes a light or dark phosphene, then one might expect that the delay effect
      might vary according to whether monkeys are required to detect a light or a dark
      visual target. For instance, if the stimulation is activating V1 elements coding
      for a light visual stimulus but not a dark visual stimulus then stimulation may
      delay saccades generated to a light target but not to a dark target. We tested
      this idea by having monkeys generate saccadic eye movements to light or dark
      visual targets immediately after the stimulation was delivered to V1. We found
      that the delay effect induced by stimulation varied with target contrast, but
      remained invariant to whether a bright or dark visual target was presented in the
      receptive field of the stimulated neurons. The significance of these results is
      discussed with regard to using monkeys to develop a visual prosthesis for the
      blind.

PMID- 15942739
TI  - Representational momentum in spatial hearing does not depend on eye movements.
AB  - The perceived final position of a moving object usually seems to be displaced in
      the direction of motion. This displacement effect, termed representational
      momentum, has been reported for both visual and acoustic targets. This study
      investigated whether representational momentum in the auditory modality depends
      on oculomotor behavior during target presentation. In a dark anechoic
      environment, subjects localized the final position of a horizontally moving
      acoustic target (continuous noise) by using a hand pointer. Subjects were
      instructed to pursue the acoustic target with their eyes, to maintain central
      gaze direction, or to fixate a central visual fixation point. Forward
      displacements of the perceived final target position occurred irrespective of the
      eye-movement condition. This result is not consistent with previous findings in
      the visual modality indicating a reduction of forward displacement for
      continuously moving targets with fixation. It is suggested that factors other
      than oculomotor behavior are the source of representational momentum in spatial
      hearing.

PMID- 15942740
TI  - Endorectal ultrasound-directed biopsy: a useful technique to detect local
      recurrence of rectal cancer.
AB  - AIMS: This study assesses the value of endorectal ultrasound (ERUS)-directed
      biopsy in detecting local recurrence of rectal cancer. METHODS: We reviewed the
      records of patients undergoing ERUS by a single surgeon for surveillance after
      treatment of rectal adenocarcinoma. Lesions suggestive of local recurrence
      underwent ERUS-assisted core-needle biopsy (EAB) via a proctoscope after precise
      ERUS localization or direct ERUS-guided biopsy (EGB) via a B&K Medical probe.
      RESULTS: From 1991 to 2003, 525 patients underwent 2,490 surveillance ERUS. Of
      these patients, 51 underwent 62 biopsy sessions: 36 EGB and 26 EAB. The mean age
      of patients was 67.2 years (range 38-93 years); 22 (43%) were female. Only 11
      patients (22%) had undergone prior radical resection of their primary tumor. No
      patient experienced a complication from the biopsies despite five being
      anticoagulated. Of 39 patients whose cancer recurrence was documented during
      follow-up, 32 (82%) were diagnosed at the initial biopsy session, and in five
      (13%), recurrence was detected only with ERUS. The combined sensitivity,
      specificity, and accuracy of EAB and EGB in detecting recurrence was 83, 100, and
      87%, respectively. In 26 patients with local recurrence, resection was performed
      with curative intent. CONCLUSION: ERUS with biopsy is useful in detecting local
      recurrence after treatment of rectal cancer. It is safe, with a high diagnostic
      yield. It may be particularly useful in patients at higher risk for local
      recurrence (i.e., after endocavitary radiation and local excision) and may allow
      early detection of local recurrence, thereby permitting attempts at curative
      resection.

PMID- 15942741
TI  - Combining systemic chemotherapy with chemoembolization in the treatment of
      unresectable hepatic metastases from colorectal cancer.
AB  - Treatment of liver metastases from colorectal cancer include surgical resection,
      radiation, hepatic chemoembolization, immunotherapy and intravenous chemotherapy.
      Complete surgical resection of liver metastases is feasible only for solitary or
      unilobar metastasis. Unresectable hepatic metastases of colorectal origin are
      resistant to radiation and immunotherapy, and the unsatisfactory results of
      systemic chemotherapy and chemoembolization have led to more aggressive
      treatment. A new method that combines systemic chemotherapy and chemoembolization
      is proposed. In this study, data from a total of 40 patients with unresectable
      hepatic metastasis from colorectal cancer were collected. All of these patients
      received combined chemoembolization and systemic chemotherapy. Embolization was
      performed by the selective cannulation of right and left hepatic artery. Equal
      amounts of a mixture of 10 ml lipiodol, 1,500 mg 5-fluorouracil (5-FU) and 15 mg
      leucovorin was deployed selectively in equal parts into the main right and left
      hepatic artery. Two weeks following chemoembolization, patients underwent
      systemic chemotherapy with 2,600 mg/m2 5-FU continuous infusion for 24 h and
      received 150 mg leucovorin intravenous bolus. The course of chemotherapy was
      repeated weekly for 24 weeks. The median follow-up period was 27 months (range 10
      36 months). Following the intention-to-treat principle, the objective tumor
      response rate was 47.5%. The median disease-free interval was 12 months and the
      median survival time was 16 months. Most of the patients (73%) died of hepatic
      failure, while the second largest group died of abdominal carcinomatosis. In
      conclusion, the results of this study are of sufficient interest to justify
      future randomized trials.

PMID- 15942742
TI  - Retained loose linear cutter staples after laparoscopic appendectomy as the cause
      of mechanical small bowel obstruction.

PMID- 15942743
TI  - A rare case of abdominal actinomycosis presenting as an inflammatory
      pseudotumour.

PMID- 15942744
TI  - Knee joint kinaesthesia and neuromuscular coordination during three phases of the
      menstrual cycle in moderately active women.
AB  - An increased incidence of sports related injuries in the premenstrual phase as
      well as in the menstrual phase of the menstrual cycle has been described. This
      may be explained by alterations in proprioception and neuromuscular coordination
      due to hormonal variations. Prospective, within women analysis of knee joint
      kinesthesia and neuromuscular coordination were performed by repeated measures
      analysis of variance in three hormonally verified phases of three consecutive
      menstrual cycles. Thirty-two healthy, moderately active female subjects
      volunteered to participate in the study. Twenty-five of the subjects performed at
      least one hormonally verified menstrual cycle. A specially designed device was
      used to investigate knee joint kinaesthesia and neuromuscular coordination was
      measured with the square hop test. These tests were carried out in the menstrual
      phase, ovulation phase and premenstrual phase determined by hormone analyses in
      three consecutive menstrual cycles. An impaired knee joint kinaesthesia was
      detected in the premenstrual phase and the performance of square hop test was
      significantly improved in the ovulation phase compared to the other two phases.
      The results of this study indicate that the variation of sex hormones in the
      menstrual cycle has an effect on performance of knee joint kinaesthesia and
      neuromuscular coordination.

PMID- 15942745
TI  - Gravity-assisted pivot-shift test for anterior cruciate ligament injury: a new
      procedure to detect anterolateral rotatory instability of the knee joint.
AB  - The denominated gravity-assisted pivot-shift test was introduced as a new
      procedure to detect anterolateral rotatory instability of the knee joint. The
      patient lies in the supine position or slightly rotated onto the affected side.
      The affected knee flexed approximately 60 degrees and the ipsilateral hip flexed,
      abducted and externally rotated so that the plane of the knee motion runs
      parallel to the floor. The examiner instructs the patient to raise the affected
      leg off the examining table and to extend the affected knee gradually. If the
      lower leg is internally rotated suddenly, with the knee subluxated at an angle of
      approximately 20 degrees , followed by the reduction in flexion, this test is
      regarded as positive. This test was investigated on 51 anterior cruciate ligament
      (ACL) deficient knees, being positive in 30 knees (Group P) and negative in 21
      (Group N) with the positive rate of 59%. There was no significant correlation
      between the result of this test and the clinical features, but Group N included
      relatively small number of females and recurrent injuries tended to occur more
      frequently in Group P. Thirty-six knees received ACL reconstruction subsequently.
      There was no statistically significant difference between the groups in the side
      to-side difference in anterior knee laxity at one year postoperatively. However,
      three patients with the side-to side difference of more than 3 mm belonged to
      Group P. Relatively low positive rate in ACL deficient knees suggests that it may
      not be used as a diagnostic procedure for ACL injury. It is possibly used for the
      prediction of high risk patients for symptomatic giving-way and/or patients with
      poor prognosis after ACL reconstruction.

PMID- 15942746
TI  - Not all "mucinous carcinomas" are equal: time to redefine and reinvestigate the
      biologic significance of mucin types and patterns in the GI tract.

PMID- 15942748
TI  - [Chronic pain patient's acceptance and satisfaction with their analgesic
      medication. Development and validation of the QAMPAS questionnaire].
AB  - BACKGROUND: A newly developed questionnaire to measure the satisfaction of
      chronic pain patients with their analgetic treatment is introduced. METHODS:
      Based on pilot studies, a multidimensional questionnaire (QAMPAS) for the
      measurement of patient satisfaction was developed. In addition to a module on
      general patient satisfaction, it includes two specific modules with regard to
      medical treatment using tablets and transdermal systems (patches). In a
      validation study the questionnaire was administered at two measurement points to
      ambulatory chronic pain patients. RESULTS: The QAMPAS subscales possess
      satisfactory psychometric properties. Medication-specific satisfaction shows a
      well-differentiated multidimensional structure. With minor limitations,
      correlations with the general patient satisfaction module and the SF-36 and BPI
      subscales indicate it to be a valid instrument. CONCLUSION: The QAMPAS
      questionnaire is a standardized instrument with satisfactory psychometric
      properties for the measurement of patient satisfaction with their analgesic
      treatment.

PMID- 15942747
TI  - Overexpression of carbonic anhydrase-related protein XI promotes proliferation
      and invasion of gastrointestinal stromal tumors.
AB  - Three isoforms of carbonic anhydrase-related protein (CA-RP) are evolutionally
      well conserved among the CA gene family but lack classical CA activity. Although
      the biological function of CA-RPs is unknown, overexpression of CA-RP VIII has
      been reported in certain tumor types. Based on the finding that CA-RPs are
      commonly expressed in the neuronal cells, we investigated expression of all three
      CA-RPs in gastrointestinal stromal tumor (GIST). In contrast to no detectable
      signal of any of the three CA-RPs in intestinal cells of Cajal,
      immunohistochemical analysis showed distinct cytoplasmic expressions of CA-RPs
      VIII and XI in 13 (59%) and 20 (91%) of 22 GIST tissue specimens, respectively.
      The positive signals for both CA-RPs VIII and XI were more intense in the
      periphery than in the central part of GISTs, whereas no significant signal for CA
      RP X expression was observed in any of the GISTs. These expression patterns of CA
      RPs were consistently observed by reverse transcription-polymerase chain reaction
      Southern blot and immunocytochemistry in the cultured GIST cell line GIST-T1.
      Ectopic expression of CA-RP XI in GIST-T1 cells induced cell proliferation and
      invasion in vitro. These findings indicate that CA-RP XI plays a role in the
      development of GIST.

PMID- 15942749
TI  - Integrin expression in developing human salivary glands.
AB  - The development and complete differentiation of salivary glands is a complex
      process that involves a large number of co-ordinated events. Little is known
      about the molecular basis for salivary gland development. However, we have
      reported previously that integrins appear to play a role. Integrins are
      heterodimeric transmembrane receptors consisting of one alpha and one beta
      subunit that play a pivotal role in the interaction of cells with the
      extracellular matrix. Such interactions regulate the organisation of cells of
      tissues and organs during development as well as cell proliferation and
      differentiation. Using immunohistochemistry and Western and Northern blot
      analysis, we mapped the localisation and expression of integrins beta1, beta3 and
      beta4 in human salivary glands obtained from foetuses ranging from weeks 4-24 of
      gestation and compared it with adult salivary glands. Integrin beta1 first
      appeared during the canalisation stage and during the differentiation stage. A
      message first appeared at week 6 of development. The expression of beta4 integrin
      protein and message was observed only in the late stage of differentiation.
      Integrin beta3 was not detected in the developing glands; however, integrins
      beta1, beta3 and beta4 were all expressed in adult salivary gland tissues. The
      data suggest that integrins, particularly beta1, have a role to play in salivary
      gland development and differentiation.

PMID- 15942750
TI  - [University clinics in the competitive hospital market].
AB  - In recent years Germany has faced a growing economization and competition among
      hospitals. To protect their interests hospitals have to operate similarly to
      other commercial businesses. Academic hospitals face difficult circumstances in
      this competition. They have to facilitate research and education activities which
      require additional financial and personnel resources but also provide maximum
      acute care treatment at all times. This causes additional disadvantages in terms
      of financial resources, compared to private hospital chains. Such examples of
      financial shortcomings have led to the privatization of academic research centres
      in Germany. An alternative strategy to privatization of academic acute care
      hospitals is the change of their legal status into a capital company or into a
      foundation, according to US experiences. Public private partnerships (PPPs) may
      also represent a potential alternative, as they have already produced a growing
      number of successful examples in the public sector in Germany. Academic acute
      care hospitals can also choose a strategic reorganization of their targets,
      similar to their privately held competitors in the market. Potential economies in
      scale may be achieved in areas such as medical treatment, research and personnel
      planning.However, it is vital that academic acute care hospitals start to act
      productively and also individually. This article provides a number of managerial
      pathways and options to maintain and strengthen operational competitiveness.

PMID- 15942751
TI  - [Management of oropharyngeal dysphagia. Current status].
AB  - The diagnostics and therapy of oropharyngeal dysphagia fall within the competence
      of ENT, phoniatrics and speech language pathology. Due to etiologic diversity,
      interdisciplinary management is necessary in many cases. After taking a thorough
      history, focused on swallowing, dynamic instrumental examination methods, i.e.
      videoendoscopic and videofluoroscopic swallowing studies, allow an evaluation of
      the morphology and function of the act of swallowing. Videoendoscopic swallowing
      studies enable the ENT specialist/phoniatrician to decide on further diagnostic
      steps, to establish a therapy and to recommend the type of feeding (oral, non
      oral). Therefore, in clinical routine, knowledge of the diagnostics and therapy
      of swallowing disorders is indispensable for the ENT specialist/phoniatrician.

PMID- 15942752
TI  - [Intractable and atypical benign paroxysmal vertigo. Pathological results of high
      resolution three-dimensional MR-tomography of the vestibular organ].
AB  - Benign paroxysmal positional vertigo (BPPV) is the most frequent vestibular
      disorder and a most common cause of dizziness and vertigo. The modern
      canalolithiasis theory postulates the existence of free-floating dense otolithic
      particles in the endolymph of the posterior semicircular canal. The symptoms were
      exactly described by Dix and Hallpike; BPPV is normally a self-limited disease
      with spontaneous recovery. There is however a small number of patients who do not
      respond to any treatment or who present with otolithic vertigo which does not fit
      all Dix-Hallpike criteria (atypical BPPV). While BPPV in its typical appearance
      cannot be diagnosed with radiologic imaging, the authors succeeded in identifying
      structural changes in the vestibular organs of patients suffering from
      intractable or atypical BPPV using three-dimensional magnetic resonance imaging.

PMID- 15942753
TI  - Cloning and molecular characterization of B-hordeins from Hordeum chilense (Roem.
      et Schult.).
AB  - One of the main limitations of cereal breeding is the lack of genetic variability
      within cultivated crops. Hordeum chilense is a wild relative of Hordeum vulgare,
      which has been successfully used in the synthesis of amphiploids by crossing with
      Triticum spp. Among the agronomic traits of these new amphiploids, the allelic
      variation in the endosperm storage proteins and their influence on breadmaking
      and malting quality are of special interest. B-hordeins are sulfur rich
      prolamins, which account for 70-80% of the total hordein fraction in barley. In
      this work, rapid amplification of cDNA ends by PCR (RACE-PCR) has been used for
      the cloning of the full-length open reading frame (ORF) of six sequences of B3
      hordeins from two lines of H. chilense. Two consensus sequences of 813 and 822 bp
      for the H1 and H7 lines, respectively, were determined by alignment of all the
      sequences generated. Between both lines, differences involving single base
      changes, which could correspond to single nucleotide polymorphisms (SNP),
      insertions and deletions were observed. Of these differences, only six out of the
      13 within the ORF caused a change of amino acid. Two insertions/deletions of 9
      and 12 bp were also observed between both lines. The derived amino acid sequences
      showed a similar structure to the B-hordeins from cultivated barley and other
      prolamins. The repetitive region is based on the repetition of the motif
      PQQPFPQQ. The copy number of the B3-hordeins was estimated as a minimum of nine
      and five copies for the H1 and H7 lines, respectively. The expression profile of
      the B-hordeins through the developing endosperm is also described in this work.
      This study of the storage proteins of H. chilense is a useful contribution to the
      knowledge of the genetic diversity available in wild relatives of cultivated
      barley. In addition, the origin of the different prolamins can be better
      understood with an in-depth knowledge of its wild equivalent.

PMID- 15942754
TI  - QTLs controlling the production of transgenic and adventitious roots in Brassica
      oleracea following treatment with Agrobacterium rhizogenes.
AB  - Brassica oleracea can be genetically engineered using Agrobacterium rhizogenes.
      The initial stage of this process is the production of transgenic ('hairy')
      roots; shoots are subsequently regenerated from these roots. Previous work using
      gus and gfp reporter genes has shown that genotypes of B. oleracea vary in their
      performance for transgenic root production. Quantitative trait loci (QTLs)
      controlling this trait have been located in one mapping population. The current
      study provides evidence that performance for transgenic root production is
      associated with performance for adventitious (non-transgenic) root production in
      B. oleracea across a second mapping population. This is shown by regression
      analyses between performance for the two traits and the demonstration that QTLs
      controlling the two traits map to the same positions within the genome. Since the
      rate of adventitious root production does not differ significantly in the
      presence and absence of A. rhizogenes, there is no evidence that the expression
      of Agrobacterium genes induces adventitious root production. It is apparent that
      genotypes exhibiting high adventitious root production in the absence of A.
      rhizogenes will also tend to show high transgenic root production, thereby
      allowing the selection of lines that are more efficiently transformed.

PMID- 15942755
TI  - Mapping and characterization of new EST-derived microsatellites for potato
      (Solanum tuberosum L.).
AB  - Microsatellites, or simple sequence repeats (SSRs) are very useful molecular
      markers for a number of plant species. They are commonly used in cultivar
      identification, plant variety protection, as anchor markers in genetic mapping,
      and in marker-assisted breeding. Early development of SSRs was hampered by the
      high cost of library screening and clone sequencing. Currently, large public SSR
      datasets exist for many crop species, but the number of publicly available,
      mapped SSRs for potato is relatively low (approximately 100). We have utilized a
      database mining approach to identify SSR-containing sequences in The Institute
      For Genomic Research Potato Gene Index database (http://www.tigr.org), focusing
      on sequences with size polymorphisms present in this dataset. Ninety-four primer
      pairs flanking SSR sequences were synthesized and used to amplify potato DNA.
      This study rendered 61 useful SSRs that were located in pre-existing genetic
      maps, fingerprinted in a set of 30 cultivars from South America, North America,
      and Europe or a combination thereof. The high proportion of success (65%) of
      expressed sequence tag-derived SSRs obtained in this work validates the use of
      transcribed sequences as a source of markers. These markers will be useful for
      genetic mapping, taxonomic studies, marker-assisted selection, and cultivar
      identification.

PMID- 15942756
TI  - Development of crop-specific transposable element (SINE) markers for studying
      gene flow from oilseed rape to wild radish.
AB  - The screening of wild populations for evidence of gene flow from a crop to a wild
      related species requires the unambiguous detection of crop genes within the
      genome of the wild species, taking into account the intraspecific variability of
      each species. If the crop and wild relatives share a common ancestor, as is the
      case for the Brassica crops and their wild relatives (subtribe Brassiceae), the
      species-specific markers needed to make this unambiguous detection are difficult
      to identify. In the model oilseed rape (Brassica napus, AACC, 2n = 38)-wild
      radish (Raphanus raphanistrum, RrRr, 2n = 18) system, we utilized the presence or
      absence of a short-interspersed element (SINE) at a given locus to develop
      oilseed rape-specific markers, as SINE insertions are irreversible. By means of
      sequence-specific amplified polymorphism (SINE-SSAP) reactions, we identified and
      cloned 67 bands specific to the oilseed rape genome and absent from that of wild
      radish. Forty-seven PCR-specific markers were developed from three combinations
      of primers anchored either in (1) the 5'- and 3'-genomic sequences flanking the
      SINE, (2) the 5'-flanking and SINE internal sequences or (3) the SINE internal
      and flanking 3'-sequences. Seventeen markers were monomorphic whatever the
      oilseed rape varieties tested, whereas 30 revealed polymorphism and behaved
      either as dominant (17) or co-dominant (13) markers. Polymorphic markers were
      mapped on 19 genomic regions assigned to ten linkage groups. The markers
      developed will be efficient tools to trace the occurrence and frequency of
      introgressions of oilseed rape genomic region within wild radish populations.

PMID- 15942757
TI  - Molecular mapping of a fertility restorer gene for Owen cytoplasmic male
      sterility in sugar beet.
AB  - We report here the molecular mapping of a fertility restorer gene (named Rf1) for
      Owen cytoplasmic male sterility in sugar beet. Eight AFLP and two RAPD markers,
      tightly linked to the Rf1 locus, were identified using bulked segregant analysis.
      Three AFLP markers, mAFEM972, mAFEM976 and mAFEM985, were found to co-segregate
      with the Rf1 allele in our mapping populations. With the help of RFLP markers,
      previously mapped on the sugar beet genome, we showed that Rf1 is positioned in
      the terminal region of linkage group Kiel III/Koeln IV. This map location agrees
      well with that found for the restorer gene X, which suggests that the Rf1 locus
      corresponds to the X locus. The availability of the molecular markers will
      facilitate the selection of maintainer-pollinator lines in breeding program and
      provide the foundation for map-based cloning of the Rf1 gene.

PMID- 15942758
TI  - Hessian fly resistance gene H13 is mapped to a distal cluster of resistance genes
      in chromosome 6DS of wheat.
AB  - H13 is inherited as a major dominant resistance gene in wheat. It was previously
      mapped to chromosome 6DL and expresses a high level of antibiosis against Hessian
      fly (Hf) [Mayetiola destructor (Say)] larvae. The objective of this study was to
      identify tightly linked molecular markers for marker-assisted selection in wheat
      breeding and as a starting point toward the map-based cloning of H13. Fifty-two
      chromosome 6D-specific microsatellite (simple sequence repeat) markers were
      tested for linkage to H13 using near-isogenic lines Molly (PI 562619) and Newton
      207, and a segregating population consisting of 192 F(2:3) families derived from
      the cross PI 372129 (Dn4) x Molly (H13). Marker Xcfd132 co-segregated with H13,
      and several other markers were tightly linked to H13 in the distal region of
      wheat chromosome 6DS. Deletion analysis assigned H13 to a small region closely
      proximal to the breakpoint of del6DS-6 (FL 0.99). Further evaluation and
      comparison of the H13-linked markers revealed that the same chromosome region may
      also contain H23 in KS89WGRC03, an unnamed H gene (H(WGRC4)) in KS89WGRC04, the
      wheat curl mite resistance gene Cmc4, and a defense response gene Ppo for
      polyphenol oxidase. Thus, these genes comprise a cluster of arthropod resistance
      genes. Marker analysis also revealed that a very small intercalary chromosomal
      segment carrying H13 was transferred from the H13 donor parent to the wheat line
      Molly.

PMID- 15942759
TI  - Development of a PVC-membrane ion-selective bulk optode, for UO2(2+) ion, based
      on tri-n-octylphosphine oxide and dibenzoylmethane.
AB  - A novel uranyl ion-selective bulk optode membrane, incorporating tri-n
      octylphosphine oxide for cation recognition and a lipophilic chromoionophore
      dibenzoylmethane, has been prepared. The PVC membrane composition was optimized
      to result in the widest working concentration range. The response range of the
      proposed optode is 4.1 x 10(-6) to 2.0 x 10(-4) mol L(-1) UO2(2+). The probe
      works at pH 4.0. Ion interference is low and selectivity, reproducibility, and
      stability are good.

PMID- 15942760
TI  - Nitrogen outputs from fecal and urine deposition of small mammals: implications
      for nitrogen cycling.
AB  - The contribution of small mammals to nitrogen cycling could have repercussions
      for the producer community in the maintaining or perhaps magnifying of nitrogen
      availability. Our objective was to model nitrogen outputs (deposition of feces
      and urine) of small mammals in an old-field ecosystem and estimate the amount of
      fecal and urinary nitrogen deposited annually. To address this objective, we used
      models from laboratory studies and combined these with data from field studies to
      estimate dietary nitrogen and monthly and annual nitrogen outputs from fecal and
      urine deposition of five rodent species. The models accounted for monthly
      fluctuations in density and biomass of small-mammal populations. We estimated
      that the minimal amount of nitrogen deposited by rodents was 1.0 (0.9-1.1) and
      2.7 (2.6-2.9) kg Nha(-1) year(-1) from feces and urine, respectively, for a total
      contribution of 3.7 (3.5-4.0) kg Nha(-1) year(-1). Hispid cotton rats (Sigmodon
      hispidus) accounted for >75% of the total nitrogen output by small mammals. Our
      estimates of annual fecal and urinary nitrogen deposited by rodents were
      comparable to nitrogen deposits by larger herbivores and other nitrogen fluxes in
      grassland ecosystems and should be considered when assessing the potential
      effects of herbivory on terrestrial nitrogen cycles.

PMID- 15942761
TI  - Mutualistic fungus promotes plant invasion into diverse communities.
AB  - Reducing the biological diversity of a community may decrease its resistance to
      invasion by exotic species. Manipulative experiments typically support this
      hypothesis but have focused mainly on one trophic level (i.e., primary
      producers). To date, we know little about how positive interactions among species
      may influence the relationship between diversity and invasibility, which suggests
      a need for research that addresses the question: under what conditions does
      diversity affect resistance to invasion? We used experimental manipulations of
      both plant diversity and the presence of an endophytic fungus to test whether a
      fungal mutualist of an invasive grass species (Lolium arundinaceum) switches the
      relationship between plant community diversity and resistance to invasion.
      Association with the fungal endophyte (Neotyphodium coenophialum) increased the
      ability of L. arundinaceum to invade communities with greater species diversity.
      In the absence of the endophyte, the initial diversity of the community
      significantly reduced the establishment of L. arundinaceum. However,
      establishment was independent of initial diversity in the presence of the
      endophyte. Fungal symbionts, like other key species, are often overlooked in
      studies of plant diversity, yet their presence may explain variation among
      studies in the effect of diversity on resistance to invasion.

PMID- 15942762
TI  - Influence of habitat, litter type, and soil invertebrates on leaf-litter
      decomposition in a fragmented Amazonian landscape.
AB  - Amazonian forest fragments and second-growth forests often differ substantially
      from undisturbed forests in their microclimate, plant-species composition, and
      soil fauna. To determine if these changes could affect litter decomposition, we
      quantified the mass loss of two contrasting leaf-litter mixtures, in the presence
      or absence of soil macroinvertebrates, and in three forest habitats. Leaf-litter
      decomposition rates in second-growth forests (>10 years old) and in fragment
      edges (<100 m from the edge) did not differ from that in the forest interior
      (>250 m from the edges of primary forests). In all three habitats, experimental
      exclusion of soil invertebrates resulted in slower decomposition rates. Faunal
      exclosure effects were stronger for litter of the primary forest, composed mostly
      of leaves of old-growth trees, than for litter of second-growth forests, which
      was dominated by leaves of successional species. The latter had a significantly
      lower initial concentration of N, higher C:N and lignin:N ratios, and decomposed
      at a slower rate than did litter from forest interiors. Our results indicate that
      land-cover changes in Amazonia affect decomposition mainly through changes in
      plant species composition, which in turn affect litter quality. Similar effects
      may occur on fragment edges, particularly on very disturbed edges, where
      successional trees become dominant. The drier microclimatic conditions in
      fragment edges and second-growth forests (>10 years old) did not appear to
      inhibit decomposition. Finally, although soil invertebrates play a key role in
      leaf-litter decomposition, we found no evidence that differences in the
      abundance, species richness, or species composition of invertebrates between
      disturbed and undisturbed forests significantly altered decomposition rates.

PMID- 15942763
TI  - Form-function analysis of the effect of canopy morphology on leaf self-shading in
      the seagrass Thalassia testudinum.
AB  - The variation in seagrass morphology and the magnitude of leaf self-shading
      within the canopy of Thalassia testudinum, were compared among nine sites in a
      fringing reef lagoon. We found a significant variation in the growth-form of T.
      testudinum reflected in a 5.4-fold variation in the attenuation coefficient (K
      (d)) within the canopy. The largest morphological variation was observed in shoot
      density. Leaf biomass, leaf area index (LAI), and shoot density were positively
      associated with canopy-K (d) and with the percentage of surface irradiance
      received by the top of the seagrass canopy (% Es). These results provide an
      explanation for the consistent pattern of depth reduction in seagrass leaf
      biomass and shoot density reported in the literature. Shoot density and shoot
      size are two descriptors of the growth-form of T. testudinum related to its
      clonal life-form. Shoot size was not significantly correlated with canopy-K (d),
      nevertheless, it showed a significant effect on the slope of the relationship
      between shoot density and canopy-K (d). According to this model, shoot size also
      contributes to light attenuation within the seagrass canopy by increasing the
      effect of shoot density. This form-function analysis suggests that light may have
      a relevant role in the regulation of the optimal plant balance between horizontal
      (variation in shoot density) and vertical (variation in shoot size) growth of
      seagrasses. Other environmental factors and interactions also need to be examined
      to fully understand the mechanistic bases of the morphological responses of
      seagrasses to the environment.

PMID- 15942764
TI  - Soil moisture redistribution as a mechanism of facilitation in savanna tree-shrub
      clusters.
AB  - Plant-soil water relations were examined in the context of a selective removal
      study conducted in tree-shrub communities occupying different but contiguous soil
      types (small discrete clusters on shallow, duplex soils versus larger, extensive
      groves on deep, sandy soils) in a subtropical savanna parkland. We (1) tested for
      the occurrence of soil moisture redistribution by hydraulic lift (HL), (2)
      determined the influence of edaphic factors on HL, and (3) evaluated the
      significance of HL for overstory tree-understory shrub interactions. Diel cycling
      and nocturnal increases in soil water potential (Psisoil), characteristic
      signatures of HL, occurred intermittently throughout an annual growth cycle in
      both communities over a range of moisture levels (Psisoil=-0.5 to -6.0 MPa) but
      only when soils were distinctly stratified with depth (dry surface/wet deep soil
      layers). The magnitude of mean (+/-SE) diel fluctuations in Psisoil (0.19+/-0.01
      MPa) did not differ on the two community types, though HL occurred more
      frequently in groves (deep soils) than clusters (shallow soils). Selective
      removal of either Prosopis glandulosa overstory or mixed-species shrub understory
      reduced the frequency of HL, indicating that Prosopis and at least one other
      woody species was conducting HL. For Zanthoxylum fagara, a shallow-rooted
      understory shrub, Prosopis removal from clusters decreased leaf water potential
      (Psileaf) and net CO2 exchange (A) during periods of HL. In contrast, overstory
      removal had neutral to positive effects on more deeply-rooted shrub species
      (Berberis trifoliolata and Condalia hookeri). Removal of the shrub understory in
      groves increased A in the overstory Prosopis. Results indicate the following: (a)
      HL is common but temporally dynamic in these savanna tree-shrub communities; (b)
      edaphic factors influencing the degree of overstory/understory development,
      rooting patterns and soil moisture distribution influence HL; (c) net
      interactions between overstory and understory elements in these woody patches can
      be positive, negative and neutral over an annual cycle, and (d) Prosopis-mediated
      HL is an important mechanism of faciliation for some, but not all, understory
      shrubs.

PMID- 15942765
TI  - Acute EPOC response in women to circuit training and treadmill exercise of
      matched oxygen consumption.
AB  - The purpose of the study was to evaluate the effects of circuit training (CT) and
      treadmill exercise performed at matched rates of oxygen consumption and exercise
      duration on elevated post-exercise oxygen consumption (EPOC) in untrained women,
      while controlling for the menstrual cycle. Eight, untrained females (31.3 +/- 9.1
      years; 2.04 +/- 0.26 l min(-1) estimated VO2max; BMI=24.6+/-3.9 kg/m2)
      volunteered to participate in the study. Testing was performed during the early
      follicular phase for each subject to minimize hormonal variability between tests.
      Subjects performed two exercise sessions approximately 28 days apart. Resting,
      supine energy expenditure was measured for 30 min preceding exercise and for 1 h
      after completion of exercise. Respiratory gas exchange data were collected
      continuously during rest and exercise periods via indirect calorimetry. CT
      consisted of three sets of eight common resistance exercises. Pre-exercise and
      exercise oxygen consumption was not different between testing days (P>0.05).
      Thus, exercise conditions were appropriately matched. Analysis of EPOC data
      revealed that CT resulted in a significantly higher (p<0.05) oxygen uptake during
      the first 30 min of recovery (0.27 +/- 0.01 l min(-1) vs 0.23+/-0.01 l min(-1));
      though, at 60 min, treatment differences were not present. Mean VO2 remained
      significantly higher (0.231 +/- 0.01 l min(-1)) than pre-exercise measures (0.193
      +/- 0.01 l min(-1)) throughout the 60-min EPOC period (p<0.05). Heart rate, RPE,
      V(E) and RER were all significantly greater during CT (p<0.05). When exercise VO2
      and exercise duration were matched, CT was associated with a greater metabolic
      disturbance and cost during the early phases of EPOC.

PMID- 15942766
TI  - Influence of exercise duration on post-exercise steroid hormone responses in
      trained males.
AB  - The purpose of this study was to systematically evaluate the effect of endurance
      exercise duration on hormone concentrations in male subjects while controlling
      for exercise intensity and training status. Eight endurance-trained males (19-49
      years) completed a resting control session and three treadmill runs of 40, 80,
      and 120 min at 55% of VO2max . Blood samples were drawn before the session and
      then 1, 2, 3 and 4 h after the start of the run. Plasma was analyzed for
      luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), cortisol, and
      free and total testosterone. LH was significantly greater at rest compared to the
      running sessions. Both free and total testosterone generally increased in the
      first hour of the 80 and 120 min runs and then showed a trend for a steady
      decline for the next 3 h of recovery. Dehydroepiandrosterone sulfate increased in
      a dose-response manner with the greatest increases observed during the 120-min
      run, followed by the 80-min run. Cortisol only increased in response to the 120
      min run and showed a decline across time in all other sessions. The ratios of
      anabolic hormones (testosterone and DHEAS) to cortisol were greater during the
      resting session and the 40-min run compared to the longer runs. The results
      indicate that exercise duration has independent effects on the hormonal response
      to endurance exercise. At a low intensity, longer duration runs are necessary to
      stimulate increased levels of testosterone, DHEAS and cortisol and beyond 80 min
      of running there is a shift to a more catabolic hormonal environment.

PMID- 15942767
TI  - Effects of concurrent inspiratory and expiratory muscle training on respiratory
      and exercise performance in competitive swimmers.
AB  - The efficiency of the respiratory system presents significant limitations on the
      body's ability to perform exercise due to the effects of the increased work of
      breathing, respiratory muscle fatigue, and dyspnoea. Respiratory muscle training
      is an intervention that may be able to address these limitations, but the impact
      of respiratory muscle training on exercise performance remains controversial.
      Therefore, in this study we evaluated the effects of a 12-week (10 sessions week(
      1)) concurrent inspiratory and expiratory muscle training (CRMT) program in 34
      adolescent competitive swimmers. The CRMT program consisted of 6 weeks during
      which the experimental group (E, n = 17) performed CRMT and the sham group (S, n
      = 17) performed sham CRMT, followed by 6 weeks when the E and S groups performed
      CRMT of differing intensities. CRMT training resulted in a significant
      improvement in forced inspiratory volume in 1 s (FIV1.0) (P = 0.050) and forced
      expiratory volume in 1 s (FEV1.0) (P = 0.045) in the E group, which exceeded the
      S group's results. Significant improvements in pulmonary function, breathing
      power, and chemoreflex ventilation threshold were observed in both groups, and
      there was a trend toward an improvement in swimming critical speed after 12 weeks
      of training (P = 0.08). We concluded that although swim training results in
      attenuation of the ventilatory response to hypercapnia and in improvements in
      pulmonary function and sustainable breathing power, supplemental respiratory
      muscle training has no additional effect except on dynamic pulmonary function
      variables.

PMID- 15942768
TI  - Body composition is related to increase in plasma adiponectin levels rather than
      training in young obese men.
AB  - We assessed the major factors regulating adiponectin levels and the influence of
      exercise training on adiponectin levels in young obese men (19.2 +/- 1.1 yrs,
      BMI: 31.1 +/- 4.2, %fat: 27.2 +/- 3.9%). Subjects were separated into three
      groups (aerobic exercise group [AE: n=7], aerobic and resistance exercise group
      [AE + RE: n = 7], control group [n = 7]). AE underwent an 8-week training program
      (three times per week, more than 30 min endurance exercise at ventilatory
      threshold (VT) intensity). AE + RE went through resistance exercise two or three
      times per week together with the above endurance exercise for 5 months. Prior to
      intervention (n = 21), adiponectin levels were significantly correlated with
      percentage of fat. Stepwise multiple regression analysis revealed that percent
      body fat was an independent predictor of basal adiponectin levels (r2 = 0.370;
      P<0.01). After intervention, fat mass, and VT were significantly improved in AE.
      AE + RE exhibited significant reduction in weight, BMI, percent body fat and fat
      mass, and had significantly increased VT, VO2max cycling power and torque.
      Insulin was not changed in both groups. The control group exhibited no
      significant change in any variables. Although adiponectin levels were unchanged
      in the three groups, a significant negative correlation between delta fat mass
      and delta adiponectin levels was observed (n = 21, r = -0.461, P<0.05). In
      addition, delta percent body fat was an independent predictor of delta
      adiponectin levels (r2 = 0.327, P<0.05). These findings indicate that for
      increasing the adiponectin level, improvement of the body composition of young
      obese men is more important than the way training is performed.

PMID- 15942769
TI  - Surface EMG and mechanomyogram disclose isokinetic training effects on quadriceps
      muscle in elderly people.
AB  - Maximum voluntary contraction (MVC) and cross-sectional area (CSA) of fast and
      slow twitch fibers are reduced in the lower limb muscles of elderly subjects.
      Isokinetic training at medium and high velocities has been widely used to improve
      muscle performance and force in young as well as elderly subjects. EMG and
      mechanomyogram (MMG) are compound signals in which the electrical and mechanical
      activities of recruited motor units (MUs) are summated. The aim of the present
      study was to verify the hypothesis that isokinetic training in the elderly
      induces changes in EMG and MMG parameters, compatible with a functional retrieval
      of fast twitch fiber MUs. In ten sedentary males (62-78 years), the surface EMG
      and MMG were recorded from the vastus lateralis muscle during isometric
      contractions at 20, 40, 60, 80 and 100% of the MVC, before and after 12 weeks of
      isokinetic training (six series of ten repetitions, each at an angular velocity
      of 2.09 rad s(-1) and 4.19 rad s(-1), two times a week). With training: (a) MVC
      and CSA increased by about 35+/-5% and 8+/-1%, respectively (P<0.05); (b) the
      ratio MVC/CSA increased significantly in all subjects by 25+/-5%; (c) the EMG
      root mean square and MMG spectral mean frequency increased significantly at the
      highest workloads. In conclusion, our data indicate that isokinetic training in
      the elderly improved muscle size and performance significantly. The EMG and MMG
      changes suggest that these results may be due to a retrieval of the fast twitch
      fiber MUs, contributing to muscle action.

PMID- 15942770
TI  - Age-associated alteration of sympatho-vagal balance in a female population
      assessed through the tone-entropy analysis.
AB  - Through our recent studies on heart rate variability (Oida et al. J Appl Physiol
      82:1794-1801, 1997; J Gerontol 54A:M219-M224, 1999a; Acta Physiol Scand 165:129
      134, 1999b; Acta Physiol Scand 165:421-422, 1999c), we discover that autonomic
      functions could be assessed quantitatively in time domain by the tone-entropy (T
      E) methodology, where the tone represents sympatho-vagal balance, and the
      entropy, autonomic regulatory activity. The purpose of this study was then to
      elucidate an age-associated alteration of sympatho-vagal balance in a female
      population through this T-E method. ECG R-R time intervals at rest were acquired
      on 10 min for 73 female subjects. Ageing influence was examined by comparisons
      between two groups: middle-aged group (40-50), (51.5 +/- 0.7 year, n = 28) and
      old-aged (60-70), (69.5 +/- 0.8 year, n = 45)]. Evaluated tone: [-0.058 +/- 0.011
      (40-50), and 0.027 +/- 0.003 (60-70) (P < 0.01)], and entropy: [3.46 +/- 0.11 (40
      50), and 3.06 +/- 0.08 bit (60-70) (P<0.01)]. The result showed that the tone was
      high and the entropy was low in the old-aged compared with the middle-aged group.
      When the result was plotted in two-dimensional T-E space, it revealed a curvi
      linear relation between the tone and the entropy, consistent with our previous
      studies on pharmacological blockades, on heart recovery after dynamic exercise
      and on a male ageing. In conclusion, the result suggested that the sympatho-vagal
      balance altered or the vagal predominance was impaired with age significantly in
      this female population. Interestingly, comparing with corresponding male, the
      female had better autonomic functions.

PMID- 15942772
TI  - Studies on inspiratory and expiratory glossopharyngeal breathing in breath-hold
      divers employing magnetic resonance imaging and spirometry.
AB  - Competitive breath-hold divers use glossopharyngeal breathing in order to
      increase their performance. Glossopharyngeal inhalation (GI) increases the volume
      of air in the lungs above the total lung capacity, thereby increasing the volume
      of gas available for pressure equalization at great depth. The reverse procedure,
      glossopharyngeal exhalation (GE), is used to suck air out of the lungs at great
      depth when the lungs are compressed, thus providing air in the mouth for
      equalization of pressure in the middle ear. Five Swedish apnea athletes were
      tested. Their vital capacity (VC) and the volume of air exhaled after GI were
      measured with a turbine spirometer, while the residual volume (RV), and the
      volume of gas in the lungs following GE was determined using a helium dilution
      procedure. Thereafter subjects performed these maneuvers during magnetic
      resonance imaging (MRI) of the thorax. All subjects exhibited a higher VC + GI
      (7.8-11.9l) than VC (6.2-9.5l) and lower RV-GE (1.16-1.77l) than RV (1.37-2.40l).
      MRI revealed pronounced changes in the volume of intrathoracic blood, with a
      small heart and compressed vessels following GI and the opposite, i.e., enlarged
      vessels during GE. MRI also showed an invagination of the posterior wall of the
      trachea, in connection with GE in certain subjects.

PMID- 15942771
TI  - Effect of hyperoxia on maximal O2 uptake in exercise-induced arterial hypoxaemic
      subjects.
AB  - This study focuses on the effect of hyperoxia on maximal oxygen uptake VO2max and
      maximal power (Pmax) in subjects exhibiting exercise-induced arterial hypoxemia
      (EIH) at sea level. Sixteen competing male cyclists VO2max > 60 ml.min(-1).kg(
      1)) performed exhaustive ramp exercise (cycle-ergometer) under normoxia and
      moderate hyperoxia (FIO2 = 30%). After the normoxic trial, the subjects were
      divided into those demonstrating EIH during exercise [arterial O2 desaturation
      (delta SaO2) >5%; n = 9] and those who did not (n = 7). Under hyperoxia, SaO2
      raised and the increase was greater for the EIH than for the non-EIH group
      (P<0.001). VO2max improved for both groups and to a greater extent for EIH (12.8
      +/- 5.7% vs. 4.2 +/- 4.6%, P<0.01; mean+/-SD) and the increase was correlated to
      the gain in SaO2 for all subjects (r = 0.71, P<0.01). Pmax improved by 3.3 +/-
      3.3% (P<0.01) regardless of the group. These data suggest that pulmonary gas
      exchange contributes to a limitation in VO2max and power for especially EIH
      subjects.

PMID- 15942773
TI  - Modulating gene expression in stem cells without recombinant DNA and permanent
      genetic modification.
AB  - Future therapeutic applications of stem cells in regenerative medicine require
      efficient techniques for modulating gene expression. Conventionally, this is
      achieved through the use of recombinant DNA, which invariably leads to permanent
      genetic alteration to the cell. Overwhelming safety and ethical concerns are
      likely to preclude the application of genetically modified stem cells in human
      clinical therapy for the foreseeable near future. An alternative may be to adopt
      a "milieu-based" approach to influence gene expression, by exposing stem cells to
      a cocktail of exogenous cytokines, growth factors, and extracellular matrix.
      Nevertheless, the non-specific pleiotropic effects exerted by various cytokines,
      growth factors, and extracellular matrix would make this a relatively inefficient
      approach. Moreover, a "milieu-based" approach is likely to require extended
      durations of in vitro culture, which might delay autologous transplantation of
      adult stem cells to the patient and might alter their immunogenicity through
      prolonged exposure to xenogenic proteins within the culture milieu. The obvious
      solution would be to deliver proteins, RNA, or their synthetic analogs, such as
      peptide nucleic acid, directly into the cell to modulate gene expression.
      Currently, two promising delivery platforms are available: (1) protein
      transduction domains, and (2) immunoliposomes. Because such molecules have a
      limited active half-life in the cytosol and are obviously not incorporated into
      the genetic code of the cell, these would only exert a transient modulatory
      effect on gene expression. Nevertheless, a transient effect may be preferable for
      clinical therapy, since this would ultimately avoid permanent genetic alteration
      to the cell.

PMID- 15942774
TI  - Effects of aging on cadmium and tubular dysfunction markers in urine from adult
      women in non-polluted areas.
AB  - OBJECTIVES: The objectives of the present analyses were to examine if Cd and
      tubular dysfunction marker levels in urine show age-dependent changes among women
      who lived in areas with no known cadmium (Cd) pollution in Japan, and if the
      trends would be further modified by correction of analyte concentration in terms
      of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). METHODS:
      The results of urinalysis for Cd, alpha(1)-microglobulin (alpha(1)-MG), beta(2)
      microglobulin (beta(2)-MG), and N-acetyl-beta-D: -glucosaminidase (NAG)
      concentrations together with CR and SG were cited from previously established
      databases. A majority of urine samples were collected in 2000-2002 from adult
      women (mostly at 40-60 years of age) in various areas in Japan, and the
      collection was supplemented by cases of > or =60-year-old women in 2003. In
      total, 11,090 never-smoking cases were subjected to statistical analysis. The
      values as observed (e.g., Cd(ob)), together with after correction for CR (e.g.,
      Cd(cr)) or SG (e.g., Cd(sg)), were examined by linear regression analysis after
      logarithmic conversion. RESULTS: The geometric mean (GM) values for Cd were 1.10
      microg/l (as observed) or 1.32 microg/g cr (after correction for creatinine
      concentration). No increases were found in the levels of alpha(1)-MG, beta(2)-MG
      or NAG on a group basis, in agreement with the conditions that there was no known
      environmental pollution with Cd in the sampling areas. There were almost linear
      increases in logarithm of Cd, alpha(1)-MG, beta(2)-MG and NAG concentrations as
      age advanced. As CR, and to a lesser extent SG, also decreases steadily
      throughout life, the correction of the analyte concentrations for urine density
      induced substantial increases in the analyte values; i.e., the correction by CR
      and SG induced amplification of the increases by two- and 1.4-times,
      respectively, compared with the increase in non-corrected observed values.
      CONCLUSIONS: There were age-related increases in Cd and tubular dysfunction
      markers in urine among women in areas with no known Cd pollution. The increase
      was amplified two- or 1.4-times when CR or SG correction was applied,
      respectively. The observation suggests that care should be practiced in applying
      CR or SG correction, especially when evaluation of Cd exposure and resulting
      health effects is made among elderly populations.

PMID- 15942775
TI  - ["Second line" polychemotherapy in metastatic urothelial cancer of the renal
      pelvis. Persisting partial remission by 18 treatment cycles of
      gemcitabine/paclitaxel after 24 treatment cycles gemcitabine/cisplatin "stable
      disease"].
AB  - Moderate activity of systemic chemotherapy for advanced urothelial cancer has
      been reported for more than 30 years. Only with the advent of potent combination
      therapy in the mid-1980s have clinically significant response rates and prolonged
      survival been documented. Due to the small number of cases and poor prognosis,
      knowledge is scant about the therapeutic effect of "second-line" polychemotherapy
      in metastatic upper tract urothelial cancer. We report an interesting case of a
      59-year-old man suffering from urothelial cancer of the renal pelvis with
      pulmonary, lymphogenous, and bone metastases who had an unexpected response to
      "second-line" chemotherapy with only 2 treatment cycles of gemcitabine/paclitaxel
      (partial remission) after 24 treatment cycles of gemcitabine/cisplatin in "stable
      disease" with progression between the therapeutic intervals.

PMID- 15942776
TI  - [The acquired buckling-flatfoot. A foot deformity due to obesity?].
AB  - Flatfoot deformity is characterized by a multiplanar hindfoot malalignment.
      Although the etiology remains unclear, the deformity is mainly attributed to
      ligamentous laxity and dysfunction of the posterior tibial tendon. Obesity is
      thought to be a risk factor that additionally impairs hindfoot stability.
      Performing a retrospective clinical and radiological study, we compared two
      groups, each with 75 patients. One group included patients with a flatfoot
      deformity stage 2, while the other group showed no hindfoot malalignment.
      Reviewing the weight and calculating the body mass index revealed significantly
      increased values for those patients with flatfoot deformity (P=0.034 and P>0.001,
      respectively). This correlation should be considered during the decision-making
      process on surgical strategies. In obese patients with flatfoot deformity, stage
      2 soft tissue reconstruction and hindfoot osteotomies should be combined with
      hindfoot arthrodeses, i.e. subtalar fusion, to maintain sufficient and durable
      stability.

PMID- 15942778
TI  - The importance of non-invasive genetic analysis in the initial diagnostics of
      Alport syndrome in young patients.
AB  - Alport syndrome is an important hereditary disorder characterized by nephritis
      and sometimes accompanied by impairment or loss of vision and hearing. The most
      common form of Alport syndrome is an X-linked dominant trait that has been
      associated with the gene COL4A5, one of the six types of IV collagen genes. More
      than 300 different mutations have been identified in the COL4A5 gene, and appear
      randomly along the whole gene. Three novel mutations, G198E, G3189D and G669R,
      were found in 5 young patients from 3 different Slovenian families. On the basis
      of the results of our study and the existing national register of Alport syndrome
      patients, we demonstrated that non-invasive methods, such as the genetic analysis
      of collagen genes, particularly in the case of young patients with undefined
      clinical features, may be of great importance and could diminish the need for
      invasive skin and renal biopsy. Our study showed the importance of molecular
      genetic data for the purpose of providing quick and precise diagnoses for
      affected family members and their offspring, particularly small children.

PMID- 15942779
TI  - Efficacy of mycophenolate mofetil in pediatric patients with steroid-dependent
      nephrotic syndrome.
AB  - Most patients with minimal change nephrotic syndrome are steroid responsive and
      tolerate this medication. However, a substantial number of patients relapse
      frequently and become steroid dependent. These patients often require treatment
      with alternative immunosuppressive drugs to maintain remission and minimize
      steroid toxicity. Previous studies have suggested that mycophenolate mofetil is
      effective in treating these patients. However, there are limited data on the
      effectiveness of this agent in pediatric patients, specifically those with
      steroid-dependent nephrotic syndrome. The purpose of this study was to assess the
      efficacy and safety of mycophenolate mofetil therapy in children and adolescents
      with steroid-dependent nephrotic syndrome who failed other treatments. A
      retrospective chart review was performed on all patients with steroid-dependent
      nephrotic syndrome. Clinical characteristics, laboratory data and the relapse
      rate were assessed prior to and during mycophenolate mofetil treatment. Twenty
      one patients, ages 2-17 years, with steroid-dependent nephrotic syndrome who were
      treated with mycophenolate mofetil between 2001-2005 were included in this
      review. The indication for mycophenolate mofetil use was steroid dependence in 17
      and steroid toxicity in 4 patients. The mean duration of treatment was 1.0+/-0.5
      years (range: 0.2-2.0 years). Patients treated with mycophenolate mofetil had a
      reduction in relapse rate from 0.80+/-0.41 to 0.47+/-0.43 relapses per month ( P
      <0.02). Side effects were mild and mostly gastrointestinal in nature. In 1 child,
      mycophenolate mofetil was discontinued due to varicella infection and not
      restarted. The findings indicate that mycophenolate mofetil is a useful
      adjunctive therapy in the treatment of patients with steroid-dependent nephrotic
      syndrome. It lowers the relapse rate by 40% and is well tolerated by patients
      with steroid-dependent nephrotic syndrome.

PMID- 15942780
TI  - Paraoxonase, total antioxidant response, and peroxide levels in children with
      steroid-sensitive nephrotic syndrome.
AB  - Reactive oxygen species (ROS) are reported to play a role in inducing the
      proteinuria of nephrotic syndrome (NS). This study investigated paraoxonase
      (PON), total antioxidant response (TAR), and oxidant total peroxide together with
      serum proteins and lipoproteins in children with steroid-sensitive NS. The study
      included 40 children with steroid-sensitive NS (21 with acute-period NS in group
      I, 19 nonproteinuric while receiving steroids in group II) and 22 sex- and age
      matched formerly nephrotic children in remission weaned from steroids (group
      III). The following parameters were determined: total peroxide, oxidative stress
      index (OSI), PON and TAR. Serum proteins and lipoproteins were also determined.
      Patients in the active phase of NS had significantly lower PON and TAR levels and
      higher OSI and total peroxide values than those in full remission; no differences
      were found in PON, TAR, or OSI values of groups I and II. Significant
      correlations were found between PON, TAR, and total peroxide. Serum total protein
      had a significantly positive correlation with PON and negative correlation with
      total peroxide in acute-period NS patients. Our results demonstrate greater
      oxidative stress and decreased antioxidants in the active phase of steroid
      sensitive NS and while patients receive steroids than during full remission. Low
      dose alternate-day steroids do not seem to decrease oxidative stress even while
      proteinuria ceases. Despite some conflicting data increased oxidation and/or
      decreased antioxidant response may be related to the pathogenesis of steroid
      sensitive NS.

PMID- 15942781
TI  - Psychosocial rehabilitation and satisfaction with life in adults with childhood
      onset of end-stage renal disease.
AB  - Little information is available on vocational rehabilitation and satisfaction
      with the quality of life in adult patients with early onset of end-stage renal
      disease (ESRD). A sample of 39 patients (mean age =26.7+/-6, range, 18 to 43
      years, n =13 on dialysis, n =26 transplanted successfully) were required to
      report data on their vocational qualification and employment, and their degree of
      general and health-related satisfaction with life was surveyed. Data on
      psychosocial rehabilitation were collected by a structured questionnaire, whereas
      satisfaction with the quality of life was assessed with the standardized
      "Questionnaire on Satisfaction in Life (FLZ)." Fifty-eight percent of the
      patients had left school with certificates equivalent to high school graduation,
      87% had completed vocational training and 67% were in paid employment. Forty-nine
      percent lived on their own or with a partner and 72% fully or partly earned their
      own living. The mean general and health-related satisfaction with life is
      significantly reduced compared to the general population. The patients were least
      satisfied in the areas 'partnership/sexuality' and 'family life/offspring' in
      general, as well as 'physical condition' and 'ability to relax' within health
      orientated satisfaction. Final mean body height was 167.6+/-11.9 (SDS -1.54+/
      1.59) for male and 153.77+/-8.29 for female patients (SDS -1.58+/-1.54). Thirty
      six percent reported to be dissatisfied with their present body height compared
      to 4% of age-matched healthy controls. Positive perception of quality of life was
      significantly correlated to satisfaction with adult height ( r =0.41, P =0.008).
      Vocational rehabilitation of adult patients with early onset of ESRD achieves
      lower values than among the general population, however, more favorable
      percentages than among young adult patients or patients with adult onset of ESRD.
      The patients' self-evaluation of both their general and health-related quality of
      life proves to be clearly muted, which is a clear indication of the physical and
      psychological strain of living with a chronic disease.

PMID- 15942782
TI  - Effect of acute renal failure on outcome in children with severe septic shock.
AB  - Acute renal failure (ARF) requiring renal replacement therapy (RRT) has been
      associated with an excess risk of mortality in adult patients with septic shock,
      but it is unknown whether this is also applicable to pediatric patients. We
      therefore conducted a retrospective pilot study. All children presenting with
      septic shock between 1st January 1998 and 1st April 2004 were analyzed. Patients
      with fluid refractory-dopamine resistant shock, necessitating the use of
      noradrenaline, were included. ARF was defined as the deterioration of renal
      function to the extent that renal replacement therapy was required (ARF group).
      This ARF group was compared with patients without ARF (non-ARF group). Out of the
      22 children with severe septic shock, seven developed ARF. PIM2 and PRISM scores
      upon admission were comparable between both groups. Mortality rates were
      significantly higher in patients with ARF (57.1% vs 6.7%; p=0.02). Pediatric
      patients with severe septic shock developing ARF have excess mortality compared
      to pediatric patients who do not develop ARF, although on diagnosis, severity of
      underlying disease and calculated risk of mortality were comparable. A
      multicenter trial is necessary to confirm these findings and to determine the
      contribution of ARF to pediatric sepsis mortality.

PMID- 15942784
TI  - Twenty years' pediatric chronic peritoneal dialysis in Uruguay: patient and
      technique survival.
AB  - In this study we analyze the impact of the patient's socioeconomic status (SES)
      and the distance from the patient's home to the dialysis center (DPH-DC),
      classified as < or =300 km or >300 km, on the patient and technique survival of
      59 patients starting chronic peritoneal dialysis (CPD) between May 1983 and
      January 2004 at a single center in Uruguay. SES was established using Graffar's
      method. Mean duration of CPD was 38.1+/-26.0 months. Mean age at the start of CPD
      was 8.4+/-5.2 years. Overall patient and technique survival at 5 years were 86.4%
      and 77.9%, respectively. Twenty (33.8%) patients were transferred to
      hemodialysis. Eight (13.5%) patients died. The incidence of peritonitis was one
      episode every 9.1 months. There was no statistically significant difference in
      patient and technique survival between the patients in the low and high SES
      groups (p=0.72 and 0.99, respectively), and between those in the two DPH-DC
      groups, (p=0.22 and p=0.99, respectively). Logistic regression analysis confirmed
      low SES and DPH-DC >300 km are not predictors of patient death (p=0.79 and
      p=0.09, respectively) or technical failure (p=0.35 and p=0.15, respectively). No
      SES- and DPH-DC-related statistically significant differences were found in
      patient and technique survival.

PMID- 15942783
TI  - Role of the renin-angiotensin system in the development of the ureteric bud and
      renal collecting system.
AB  - Genetic, biochemical and physiological studies have demonstrated that the renin
      angiotensin system (RAS) plays a fundamental role in kidney development. All of
      the components of the RAS are expressed in the metanephros. Mutations in the
      genes encoding components of the RAS in mice or pharmacological inhibition of RAS
      in animals or humans cause diverse congenital abnormalities of the kidney and
      lower urinary tract. The latter include renal vascular abnormalities, abnormal
      glomerulogenesis, renal papillary hypoplasia, hydronephrosis, aberrant UB
      budding, duplicated collecting system, and urinary concentrating defect. Thus,
      the actions of angiotensin (ANG) II during kidney development are pleiotropic
      both spatially and temporally. Whereas the role of ANG II in renovascular and
      glomerular development has received much attention, little is known about the
      potential role of ANG II and its receptors in the morphogenesis of the collecting
      system. In this review, we discuss recent genetic and functional evidence
      gathered from transgenic knockout mice and in vitro organ and cell culture
      implicating the RAS in the development of the ureteric bud and collecting ducts.
      A novel conceptual framework has emerged from this body of work which states that
      stroma-derived ANG II elicits activation of AT(1)/AT(2) receptors expressed on
      the ureteric bud to stimulate branching morphogenesis as well as collecting duct
      elongation and papillogenesis.

PMID- 15942785
TI  - Urinary uric acid levels and discoloration of diapers in healthy neonates.

PMID- 15942786
TI  - Serum adhesion molecule profiles in children with progressive renal disorders.

PMID- 15942787
TI  - Value of urinary excretion of microalbumin in predicting glomerular lesions in
      children with isolated microscopic hematuria.
AB  - Urinary microalbumin excretion was assessed in 76 children with asymptomatic
      microscopic hematuria in whom the presence of proteinuria, hypertension, reduced
      renal function, hypercalciuria, urinary tract infection or structural abnormality
      of the urinary tract had been excluded. All children underwent a percutaneous
      kidney biopsy to determine whether microalbumin excretion can be used as a marker
      to predict the source of hematuria. Microalbumin excretion was considered normal
      if the urinary ratio of microalbumin to creatinine (MA/Cr ug/mg) was < or =30.
      Twenty-two (29%) had microalbuminuria (MA/Cr 96+/-30 microg/mg) and 54 (71%) had
      normal albumin excretion (MA/Cr 13+/-2 microg/mg). Of those with
      normoalbuminuria, 38 (70%) had normal renal tissue, 15 (28%) thin glomerular
      basement membrane (TGBM) disease and 1 (2%) IgA nephropathy. In contrast, 20
      (91%) of those with microalbuminuria had IgA nephropathy and 2 (9%) had TGBM
      disease. The mean urinary MA/Cr ratio for all IgA children was 89+/-32 microg/mg
      higher compared with a value for the children with TGBM disease (14 +/-3
      microg/mg, P <0.001) or children whose renal biopsy appeared normal (11+/-2
      microg/mg, P <0.001). Statistical analysis revealed no significant differences
      between the mean MA/Cr ug/mg ratio for children with TGBM disease and those with
      normal glomerular findings. Fourteen of the 20 children with IgA nephropathy who
      also had microalbuminuria were treated with an angiotensin-converting enzyme
      (ACE) inhibitor. Over a mean follow-up of 51 months, none developed overt
      proteinuia; hematuria resolved and microalbuminuria returned to normal in eight
      (57%) during therapy with the ACE-inhibitor. In contrast, hematuria persisted and
      prtoteinuria developed in the other untreated children. None of the children with
      TGBM disease developed overt proteinuria after a mean of 51 months. Hematuria was
      persistent in children with TGBM disease, but often resolved in those whose
      biopsies were completely normal. These data suggest that determination of urinary
      microalbumin excretion is warranted in the routine examination of children with
      isolated microscopic hematuria. Routine screening for microalbuminuria may help
      to identify a subgroup of patients with IgA nephropathy who are at high risk for
      progressive kidney disease and need more intensive therapy and closer follow-up.

PMID- 15942788
TI  - Clinical research in pediatric nephrology: state of the art.
AB  - The goals of clinical research include comparing new and standard treatments,
      establishing treatment efficacy, defining risk factors for disease, elucidating
      pathophysiologic mechanisms of disease, and establishing causation. Although the
      randomized clinical trial has been the "gold standard" in clinical research and
      is the strongest study design to establish causation for many clinical research
      questions, an interventional study or "experiment" such as a randomized trial is
      often not possible. Observational study designs also demonstrate associations
      between exposures and outcome. To determine whether these associations are likely
      to be causal, one can assess a number of qualities, first outlined by the British
      epidemiologist Sir Austin Bradford Hill. These qualities include analogy to what
      is known; the plausibility, strength and specificity of the association;
      consistency and coherence across studies; the temporality of the putative cause
      and effect; and the presence of a biological gradient. The presence of these
      factors adds weight to the probability that a given association is causal.
      Systematic reviews and meta-analyses use these factors in combining studies to
      assess whether associations are cause and effect. Additionally, new methods in
      the analysis of longitudinal data collected in observational studies can help to
      determine causation. In this review, we will use recent literature and
      contemporary topics in pediatric nephrology to illustrate state-of-the-art
      research methods using classic epidemiological elements needed to establish
      causation.

PMID- 15942789
TI  - Hypokalemic rhabdomyolysis in a child with Bartter's syndrome.
AB  - Hypokalemia represents a rare cause of rhabdomyolysis. Some reports have
      described a few adult patients affected by Bartter's syndrome and Gitelman's
      syndrome with rhabdomyolysis due to severe hypokalemia. We report the first
      pediatric patient with Bartter's syndrome in whom rhabdomyolysis developed when
      her plasma potassium level was less than 2 mEq/l. Prompt intravenous fluid and
      potassium prevented tubular damage and acute renal failure. We recommend
      determining serum creatine phosphokinase in all patients affected by Bartter's
      syndrome and profound hypokalemia.

PMID- 15942790
TI  - Bone mineral density and bone turnover in patients with Bartter syndrome.
AB  - The aim of this investigation was to evaluate bone mineral density (BMD), by use
      of DXA, and bone turnover, in patients with Bartter syndrome (BS). Ten patients
      (2 with BS type II and 8 with BS type III) were included in the procedure. Age at
      study varied between 2 and 30 years. During the studies usual treatment with
      indomethacin, spironolactone, and potassium chloride was maintained. Results were
      compared with those obtained in the 20 asymptomatic parents. Height of the
      patients at the time of the study did not differ from reference values (Z-score 
      1.2 to +0.8). Three patients (1 with BS type II and 2 with BS type III) presented
      reduced lumbar spine BMD or overt osteopenia (BMD Z-scores: -2.3, -1.3, and 
      1.1). BMD did not correlate significantly with age. Paternal and maternal femoral
      neck BMD values correlated significantly with lumbar spine BMD of the patients
      (r=0.65, P<0.05, and r=0.80, P<0.01). Lumbar spine BMD Z-scores correlated
      negatively with urinary Ca excretion when values both from patients and parents
      were jointly analyzed (r=-0.43, P<0.05). Plasma calcium concentration was
      significantly higher (P<0.001) and plasma phosphate Z-score was significantly
      lower (P<0.05) in the patients than in the parents. However, no significant
      differences were observed in values for intact PTH, 1,25 (OH)(2)D(3) and 25
      (OH)D(3). Intact PTH values correlated positively with BMD Z-scores at lumbar
      spine (r=0.45, P<0.05) and at femoral neck (r=0.63, P<0.01). Age-corrected
      biochemical markers of bone formation (plasma alkaline phosphatase and
      osteocalcin concentrations) were normal whereas age-corrected markers of bone
      reabsorption (urinary PYD and DPD excretion) were significantly higher than
      parental values (P<0.01 and <0.05, respectively). We conclude that: (1) reduced
      BMD is not an exclusive feature of neonatal BS and it can be also observed in
      classic BS; (2) the loss of bone mineral is not progressive, probably because of
      the hypocalciuric effect of indomethacin therapy; and (3) this study did not
      determine whether loss of bone mass is the cause or the consequence of
      hypercalciuria although the beneficial effect of indomethacin therapy implies the
      latter.

PMID- 15942791
TI  - Poststreptococcal glomerulonephritis with pulmonary edema and microscopic
      hematuria.

PMID- 15942792
TI  - Plasma and urinary adrenomedullin levels in children with renal parenchymal scar
      and vesicoureteral reflux.
AB  - Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and
      antiproliferative effects in renal mesangial cells, as well as diuretic and
      natriuretic actions. Its gene expression is stimulated by endotoxins
      (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels
      are known to deviate from normal levels in many renal diseases. The purpose of
      this study is to determine plasma and urinary AM levels in children with renal
      parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out
      on 74 children with recurrent urinary tract infections, arranged in groups: 25
      patients with RPS with VUR (group I), 16 patients with RPS without VUR (group
      II), 12 patients with VUR without RPS (group III) and 21 healthy children as the
      control group. Plasma and urinary AM concentrations were both determined by high
      performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per
      milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum
      creatinine, creatinine clearance and fractional sodium excretion (FE(Na)) were
      measured. All cases with RPS and VUR had normal blood pressure levels. The plasma
      AM levels were higher, although not significantly, in the control group (56.2+/
      14.0 pM/ml) than in group I (50.6+/-4.2 pM/ml), group II (49.6+/-3.7 pM/ml) and
      group III (50.6+/-3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in
      the control group (80.1+/-33.9 pM/mg) than in the three study groups (52+/-7.6
      pM/mg, 58.6+/-7.5 pM/mg and 44.2+/-6.4 pM/mg; P =0.003, P =0.002 and P =0.002,
      respectively). There were no differences among the 4 groups (group I, group II,
      group III and the control group) in terms of FE(Na) and creatinine clearance ( P
      >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels
      in patients with RPS and VUR implies that AM can be a prognostic factor in the
      long-term follow-up of cases with these diseases.

PMID- 15942793
TI  - Regulation of TauT by cisplatin in LLC-PK1 renal cells.
AB  - Cisplatin is a commonly used chemotherapeutic agent that has a major limitation
      because of its nephrotoxicity. Since cisplatin-induced renal injury is mainly
      confined to the S3 segment of renal proximal tubules-the primary site for renal
      adaptive regulation of TauT-we hypothesize that TauT functions as an anti
      apoptotic gene and plays a role in protecting renal cells from drug-induced
      nephrotoxicity. In the present study we demonstrated that expression of TauT was
      significantly reduced by cisplatin (50 muM) in LLC-PK1 cells. Down-regulation of
      TauT by cisplatin occurs at the transcriptional level in a dose-dependent manner,
      as demonstrated through a reporter gene driven by the TauT promoter. It appears
      that cisplatin down-regulates TauT expression, at least in part, through the p53
      dependent pathway, since cisplatin induces the p53 expression, which, in turn,
      represses TauT. Cisplatin induces apoptosis of LLC-PK1 cells in a dose-dependent
      manner. However, forced over-expression of TauT by stable transfection of a
      taurine transporter cDNA (pNCT) in LLC-PK1 cells was able to attenuate cisplatin
      induced down-regulation of taurine uptake by LLC-PK1 cells and protect renal
      tubular cells from apoptosis. The mechanism by which TauT serves as an anti
      apoptotic gene in cisplatin-induced renal injury remains to be determined, but
      could relate to taurine-dependent cell volume regulation.

PMID- 15942794
TI  - Acute interstitial nephritis predisposed a six-year-old girl to minimal change
      nephrotic syndrome.
AB  - A six-year-old girl was admitted to our hospital with acute renal failure. We
      made a clinical diagnosis of acute interstitial nephritis and oral corticosteroid
      therapy was started. Her renal failure soon recovered, and renal biopsy showed
      acute interstitial nephritis by light microscopy with glomerular foot process
      effacement by electron microscopy. Although her proteinuria was not heavy at the
      time of biopsy, her proteinuria subsequently increased to show nephrotic
      syndrome. We continued to give corticosteroids and her nephrotic syndrome went
      into remission 13 days after biopsy. Serological and bacteriological examination
      showed no evidence of known pathogen or drug hypersensitivity. The time changes
      in proteinuria were monitored by fractional total protein excretion (FETP) and
      fractional beta2 microglobulin excretion (FEbeta2MG) in order to evaluate the
      severity of proteinuria under different glomerular filtration rates and different
      proximal tubular functions. The results revealed that nephrotic syndrome had
      occurred during recovery from acute interstitial nephritis. This is the first
      case report to show the sequential occurrence of acute interstitial nephritis and
      nephrotic syndrome based on evidence from fractional protein excretion.

PMID- 15942795
TI  - A bone remodelling model coupling micro-damage growth and repair by 3D BMU
      activity.
AB  - Bone as most of living tissues is able, during its entire lifetime, to adapt its
      internal microstructure and subsequently its associated mechanical properties to
      its specific mechanical and physiological environment in a process commonly known
      as bone remodelling. Bone is therefore continuously renewed and micro-damage,
      accumulated by fatigue or creep, is removed minimizing the risk of fracture.
      Nevertheless, bone is not always able to repair itself completely. Actually, if
      bone repairing function is slower than micro-damage accumulation, a type of bone
      fracture, usually known as "stress fracture", can finally evolve. In this paper,
      we propose a bone remodelling continuous model able to simulate micro-damage
      growth and repair in a coupled way and able therefore to predict the occurrence
      of "stress fractures". The biological bone remodelling process is modelled in
      terms of equations that describe the activity of basic multicellular units. The
      predicted results show a good correspondence with experimental and clinical data.
      For example, in disuse, bone porosity increases until an equilibrium situation is
      achieved. In overloading, bone porosity decreases unless the damage rate is so
      high that causes resorption or "stress fracture".

PMID- 15942796
TI  - Pituitary duplication and nasopharyngeal teratoma in a newborn: CT, MRI, US and
      correlative histopathological findings.
AB  - The computed tomography and MRI imaging findings in a case of pituitary
      duplication and epipharyngeal teratoma are described in a newborn baby girl with
      respiratory difficulties. Associated skull base and central nervous system
      malformations are presented. Teratoma diagnosis was confirmed by histology. The
      embryological pathogenesis is discussed.

PMID- 15942797
TI  - Cochlear implantation in an adult patient with auditory neuropathy.
AB  - We present a case report of effective cochlear implantation for an adult patient
      with auditory neuropathy. A 34-year-old man developed bilateral hearing loss at
      approximately 10 years of age. His speech discrimination score was very severe
      despite only moderate sensorineural hearing loss. Absence of auditory brainstem
      responses (ABR) and preservation of distortion product otoacoustic emissions
      (DPOAE) were confirmed by our audiological examinations. After cochlear
      implantation, good responses for electrically evoked compound action potential
      (EAP) and electrically evoked ABR (EABR) were observed. Postoperatively, his
      audiological performance was significantly improved. We conclude that cochlear
      implantation can be a valid option for patients with auditory neuropathy.

PMID- 15942798
TI  - Sodium selenite is a potent radioprotector of the salivary glands of the rat:
      acute effects on the morphology and parenchymal function during fractioned
      irradiation.
AB  - In vitro studies show that sodium selenite is a potential radioprotector in
      normal cultural cells, but not in tumor cells. The aim of this study was to
      evaluate the cytoprotective potency of sodium selenite during a conventional
      fractioned irradiation of the salivary glands of rats. The head and neck area of
      male WAG/RijH rats was irradiated with (60)Co-gamma rays (60 Gy/30 fractions/6
      weeks). Sodium selenite (15 microg/kg body weight) was applied through a venous
      port 30 min before irradiation. Rats of a control group were treated in the same
      manner with an equal volume of physiologic sodium chloride. In the course of
      treatment, the salivary glands were resected at different stages and examined
      histopathologically. The evaluation of gland function was performed prior to and
      after radiotherapy by sialoscintigraphy. The irradiation caused dose-dependent
      damage in the salivary glands. Intra- and intercellular edema (16 Gy),
      vacuolization (30 Gy), degranulation (46 Gy) and necrosis of the acinar cells (60
      Gy) occurred. Sodium selenite delayed the development of the described damage;
      additionally, the number of necrotic acinar cells after the application of 60 Gy
      was reduced (control, 75% vs. sodium selenite, 30%). The sialoscintigaphical
      results confirmed these results: the loss in gland function in the control group
      was 74 vs. 44% (P < 0.05) in the sodium selenite group. Based on the
      morphological and sialoscintigraphical findings, a cytoprotective effect on the
      acute toxicity of the salivary glands of rats could be detected during
      irradiation with synchronous application of sodium selenite.

PMID- 15942799
TI  - Prognostic evaluation in supracricoid partial laryngectomy with cricohyoidopexy.
AB  - Identification of prognostic factors related to supracricoid partial laryngectomy
      may optimise indications for this surgical technique. We analysed several
      clinical and histopathological variables in a series of 81 patients treated with
      SPL at our department. Attention was focused on neoplastic spread of the anterior
      commissure, thyroid cartilage and prelaryngeal soft tissue of the neck.
      Statistical analysis (Kaplan-Meier method and Cox regression test) showed a
      significant decrease in survival for prelaryngeal soft tissue invasion. Due to
      the fact that the survival rate is not modified by the anterior commissure and
      thyroid cartilage infiltration, the prognostic value of prelaryngeal invasion is
      extremely relevant. Therefore, we suggest the oncological value of SPL even in
      cases of invasion of the anterior commissure or thyroid cartilage, but not beyond
      the outer perichondrium.

PMID- 15942800
TI  - Hypoplasia of the epiglottis in a middle-aged man.
AB  - Hypoplasia of the epiglottis diagnosed at adulthood is extremely rare. Most
      patients with epiglottic hypoplasia have presented life-threatening symptoms of
      respiratory distress and severe aspiration in infancy or early childhood. This is
      a case of congenital epiglottic hypoplasia found in a 42-year-old man complaining
      of mild hoarseness and throat discomfort. Strobolaryngoscopy and CT scans
      revealed a unique anomaly with isolated epiglottic hypoplasia and normal
      appearance of other laryngeal structures. This case is discussed with a review of
      the literature on this rare occurrence.

PMID- 15942801
TI  - Laser projection in high-speed glottography for high-precision measurements of
      laryngeal dimensions and dynamics.
AB  - The detection of metric dimensions of laryngeal structures yields valuable
      information for both clinical and research purposes. The use of a laser
      projection system combined with a high-speed camera system enables the derivation
      of absolute spatial dimensions of the larynx. Vocal fold length, vibratory
      amplitudes and velocity can be derived. This was shown on 13 female and 9 male
      larynges during phonation of a vowel at different pitches. The vocal fold length,
      the amplitude of oscillation and the velocity of vibration were analyzed in
      between pitches of 119 to 236 Hz in the male group and 181 to 555 Hz in the
      female group. The vocal folds' length ranged from 8.4 to 14.3 mm in the male
      group and from 7.7 to 15.6 mm in the female group. Corresponding amplitudes
      varied from 0.33 to 1.24 mm (male) and from 0.38 to 0.82 mm (female). The maximal
      velocity of vibration was between 0.48 and 0.85 m/s in males and between 0.47 and
      1.3 m/s in females without showing significant correlation between each
      parameter. The described technique enables the detection of absolute spatial
      laryngeal dimensions of female and male subjects at different pitches. Dynamic
      processes such as velocity of vibration can be quantified. The detection of
      metric data serves to optimize biomechanical model computations and provides
      valuable information in diagnostics and interpretation of organic and non-organic
      voice disorders.

PMID- 15942802
TI  - To divide or manipulate the chorda tympani in stapedotomy.
AB  - The objective of this study is to determine the nature, duration and severity of
      chorda tympani symptoms in post-stapedotomy patients when the nerve has been
      known to have either sustained surgical manipulation or division. The study
      design was retrospective and blind, based at a tertiary Otology Referral Center
      (Gloucestershire Royal Hospital). All successive patients undergoing stapedotomy
      operated upon by the senior author (JMR) between November 1991 and October 1998
      were included. The main outcome measures were postoperative graded dysgeusia
      (questionnaire) and post operative electrogustometry score, comparing the chorda
      tympani cut group and the chorda tympani preserved group. Sixty stapedotomies
      were performed in the study period. After a minimum interval of 8 months,
      questionnaire data were obtained in 55/60 (92%), and electrogustometry studies
      were carried out in 48/60 (80%). Symptoms of dysgeusia were experienced in the
      chorda tympani nerve cut (CC) group in 95% and in the chorda preserved (CP) group
      in 52%. For those with symptoms, duration was 6.7 months (+/-4.9 SD) and 3.4
      months (+/-3.7 SD) for the CC and CP groups, respectively. From the
      electrogustometry data, after 8 months, the risk of total loss of response is
      significantly higher in CC patients (94%) than in CP patients (25%) (P = 0.0001).
      Also at 8 months, 54% of CP patients had normal ipsilateral electrogustometry
      responses compared with 6% in the CC group. In conclusion, cutting the chorda
      tympani results in significantly greater symptoms than when subjected to
      manipulation only, and these symptoms are likely to be more long lasting.
      Therefore, it is our recommendation that where possible the chorda be preserved.
      The risk of severe chorda symptoms when the chorda is cut is small (<5%).
      Preoperative consent to include dysgeusia is advised.

PMID- 15942803
TI  - Cochlear implantation for treatment-induced ototoxic deafness in Langerhans cell
      histiocytosis. A case report.
AB  - A case is presented where the authors carried out a cochlear implantation on a
      girl whose deafness was induced by cytostatic agents. The normally hearing child
      was diagnosed with Langerhans cell histiocytosis at the age of 3 years and
      received polychemotherapy for almost 2 years. By her 5th year, she started to
      develop a bilateral, progressive sensorineural hearing loss, necessitating a
      hearing aid in both ears. While her histiocytosis was cured, her hearing
      ultimately deteriorated to total deafness on the right and profound hearing loss
      on the left ear. After 3 years, her hearing aids no longer provided adequate
      hearing for the postlingually deafened girl. At the age of 14, a cochlear
      implantation was performed on her right ear with excellent results.

PMID- 15942804
TI  - Multifocal adult rhabdomyoma of the head and neck: a case report and literature
      review.
AB  - Adult extracardiac rhabdomyomas are rare benign skeletal muscle tumors that most
      commonly present in the head and neck region. Only a few multifocal cases have
      been described to date in the world literature. We hereby present an additional
      multifocal case, the 14th worldwide, and review the literature.

PMID- 15942805
TI  - Long-term outcome and health-related quality of life in benign paroxysmal
      positional vertigo.
AB  - A prospective cohort study was designed to evaluate the long-term outcome and
      health-related quality of life (HRQoL) in patients with posterior canal benign
      paroxysmal positional vertigo (PC-BPPV) treated by the particle repositioning
      maneuver (PRM) in the outpatient clinic of a general community hospital. Fifty
      individuals with PC-BPPV were included, and 45 (90%) completed the study. The
      diagnosis was based on the history of short episodes of vertigo and a positional
      nystagmus during the Dix-Hallpike test (DHT). All patients were treated by a
      single PRM, and relapses were evaluated by DHT at 30, 180 and 360 days post
      treatment; a new PRM was performed if the DHT was positive. The main outcome
      measures were: percentage of patients with a negative DHT after treatment, scores
      obtained on the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36)
      and the Dizziness Handicap Inventory Short Form (DHI-S) before and 30, 180 and
      360 days post-treatment. The DHT was found negative in 80% (40/50) of individuals
      at 30 days. Ten, seven and five patients presented a positive DHT at 30, 180 and
      360 days, respectively. Persistent BPPV was observed in 5% (2/50) of patients at
      360 days, despite repeated PRM. Relapses (DH+ after successful PRM) were observed
      in 7.5% (3/50) at 180 days and 360 days. Both questionnaires showed a reliability
      Cronbach's alpha >0.7. The average standardized score for each SF-36 scale was
      compared with the reference population normative data, showing differences with
      norms for all scales except for vitality. After PRM, patients improved their
      scores with both instruments, indicating a restoration of HRQoL at 30 days.
      Physical dimension scores of the SF-36 improved from day 30 to 360. DHI-S scores
      were statistically better after PRM (P < 0.001). Our results show that the
      effectiveness of PRM is 88% after 1 year of follow-up. Patients with BPPV
      experienced a decrease in HRQoL, which was restored after PRM. Although relapses
      were observed in 7.5% of individuals, they did not affect HRQoL.

PMID- 15942806
TI  - Endothelial nitric oxide synthase/soluble guanylate cyclase system in human nasal
      polyps.
AB  - The aim of our study was to analyze the level of expression of the endothelial
      nitric oxide synthase (eNOS)/soluble guanylate cyclase (sGC) system in nasal
      polyps and control nasal mucosae. The study was performed in polyps from 15
      patients and nasal mucosae from 11 subjects operated on the nasal septum (control
      group). The expression of endothelial nitric oxide synthase (eNOS) and soluble
      guanylate cyclase (sGC) was determined in nasal mucosae. Western blot analysis
      demonstrated that eNOS protein was overexpressed in the nasal polyps with respect
      to control nasal mucosae. Immunohistochemistry also demonstrated that the
      vascular endothelium of nasal polyps contained higher amounts of eNOS protein
      than control nasal mucosae. Moreover, the beta(1) subunit of sGC was also
      overexpressed in the nasal polyps, which was associated with an increased content
      of cyclic GMP in the nasal polyps with respect to nasal control mucosae. In human
      nasal polyposis, there is an overexpression of the eNOS/sGC system. Further
      studies are needed to assess whether this overexpression is involved in the
      genesis of nasal polyposis.

PMID- 15942807
TI  - Survival of deep-sea shrimp (Alvinocaris sp.) during decompression and larval
      hatching at atmospheric pressure.
AB  - We report successful larval hatching of deep-sea shrimp after decompression to
      atmospheric pressure. Three specimens of deep-sea shrimp were collected from an
      ocean depth of 1157 m at cold-seep sites off Hatsushima Island in Sagami Bay,
      Japan, using a pressure-stat aquarium system. Phylogenetic analysis of
      Alvinocaris sp. based on cytochrome c oxidase subunit gene sequences confirmed
      that these species were a member of the genus Alvinocaris. All 3 specimens
      survived to reach atmospheric pressure conditions after stepwise 63-day
      decompression. Two of the specimens contained eggs, which hatched after 10 and 16
      days, respectively, of full decompression. Although no molting of the shrimp
      larvae was observed during 74 days of rearing under atmospheric pressure, the
      larvae developed conventional dark-adapted eyes after 15 days.

PMID- 15942808
TI  - Cyber visual training as a new method for the mastery of endoscopic surgery.
AB  - BACKGROUND: We devised a new method incorporating cyber visual training whereby
      novices in endoscopic surgery are instructed via repetition of a video-recorded
      procedure. We then conducted a study designed to investigate the impact of this
      cyber visual training on the mastery of intracorporeal knot-tying as an
      endoscopic technique. METHODS: For the cyber visual training a 10-min video of
      the same procedure was replayed at normal, slow, and rapid speeds or presented in
      a series of still images. The training was undertaken by 36 medical students and
      1st year trainee doctors who had had no experience of endoscopic surgery. They
      were divided into three groups, each of all received the same introductory
      lecture. Group A was only given training with the instructor for 15 min. Group B
      trained with the instructor for 15 min and was allowed self-training for 10 min.
      Group C viewed the cyber video beforehand and then underwent training with the
      instructor for 15 min. For all participants, the time required to complete a knot
      tying task was measured and the level of endoscopic skill before and after the
      training was assessed using a virtual reality system the minimally Invasive
      Surgical Trainer-Virtual Reality (MIST-VR), in terms of the following three
      parameters: time, errors, and efficiency of hand movements. The Steel-Dwass test
      was used to evaluate the differences among the three groups in task performance.
      RESULTS: Group C completed the knot-tying task faster than group A (p = 0.0375),
      but there were significant differences between groups A and B and groups B and C.
      There were no significant differences in the parameters assessed using the MIST
      VR. CONCLUSIONS: Our new concept of cyber visual training is effective for
      mastering the knot-tying technique. This type of training should be widely
      applicable to other procedures, such as dissection, clipping, and hemostasis.

PMID- 15942809
TI  - Robotic-assisted pelvic organ prolapse surgery.
AB  - BACKGROUND: This study describes technical aspect and short-term results of
      pelvic organ prolapse surgery using the da Vinci robotic system. METHODS: During
      a 1-year period, 18 consecutive patients with pelvic organ prolapse were operated
      on using the da-Vinci system. Clinical data were prospectively collected and
      analyzed. RESULTS: All but one procedure was successfully completed robotically
      (95%). Performed procedures were colpohysteropexy (n = 12), mesh rectopexy (n =
      2), or sutured rectopexy combined with sigmoid resection (n = 4). Average setup
      time was 21 min and significantly decreased with experience. Mean operative time
      was 172 min (range, 45-280). There were no mortality and no specific morbidity
      due to the robotic approach. Mean hospital stay was 7 days. At 6 months, all
      patients were free of pelvic organ prolapse and stated that they were satisfied
      with anatomical and functional results. CONCLUSION: Our experience indicates that
      using the da-Vinci robotic system is feasible, safe, and effective for the
      treatment of pelvic organ prolapse.

PMID- 15942810
TI  - Laparoscopic resection of congenital choledochal cyst, choledochojejunostomy, and
      extraabdominal Roux-en-Y anastomosis.
AB  - BACKGROUND: The feasibility of laparoscopic resection of choledochal cyst and
      hepaticojejunostomy in children is still unclear. This report presents the
      author's experience with a first series of patients. METHODS: Data from 11
      consecutive children (median age 17.5 months, SD 22, range 2 to 70) with
      choledochal cyst scheduled for laparoscopy were collected prospectively. There
      were nine type I and 2 type V cysts according to Todani's classification. All
      except one patient had intermittent jaundice or recurrent pancreatitis. The
      laparoscopic technique included excision of the cyst. A Roux-en-Y anastomosis was
      constructed after exteriorization of the small bowel via the infraumbilical
      trocar incision. After repositioning of the bowel an end-to-side
      hepaticojejunostomy was carried out laparoscopically. RESULTS: The procedures
      were carried out in nine children without intraoperative events and a median
      duration of 289 min (SD 62). In two patients, the operation was converted after
      60 and 90 min due to a lack of overview at the dorsal margin with problems in
      separation of the portal vein. Oral food intake was started within 2 days and
      tolerated well in all except one patient, in whom biliar fluid from the drain led
      to laparoscopic reevaluation on day 1. A small leak was resutured and the patient
      was discharged on day 5. In one patient, recurrent cholangitis and a dilated Roux
      en-Y loop led to correction of some kinking of the loop via laparotomy after 3
      months. All other patients are well with bile-stained stools after a mean follow
      up of 13 months. CONCLUSIONS: Laparoscopic resection of congenital choledochal
      cyst and choledochojejunostomy in children is feasible. We feel that there is a
      considerable learning curve with the technique. Future studies will have to prove
      the feasibility of laparoscopic Roux-en-Y bowel anastomosis without the need for
      bowel exteriorization.

PMID- 15942811
TI  - Laser photoablation of colorectal adenomas: a 12-year experience.
AB  - BACKGROUND: We analyze laser photoablation as an alternative treatment of large
      sessile polyps in inoperable patients. METHODS: Ninety-four colorectal polyps
      (mean diameter 3.09 +/- 2.7 cm, range 1-15 cm) were treated using high-energy
      lasers (Nd:YAG and diode). Grade of dysplasia was low in 51, high in 35, with
      focally invasive cancer in eight. RESULTS: After 405 laser sessions (4.3 per
      polyp) five procedure-related complications were observed: two strictures, two
      bleedings, and one perforation. The last needed a surgical resection; the others
      were successfully treated by endoscopic therapy. Fifty-seven polyps (61%) were
      completely eradicated and the growth was controlled in all but two (98%). No
      degeneration was found after 28-month follow-up of treated adenomas with low- or
      high-grade dysplasia. Outcome of treatment was dependent on the dimension and
      grade of the dysplasia (p < 0.05), but not on the polyps' position (rectum or
      colon). Relief of rectal bleeding was obtained in 90%, of mucus discharge in 77%,
      and of tenesmus in 100% of cases. CONCLUSIONS: Laser photoablation of colonic
      adenomas can be considered a valid procedure not only to relieve symptoms, but
      also to control the risk of degeneration in patients unfit for surgery or when
      surgical treatment is considered excessively invalidating.

PMID- 15942813
TI  - Seasonal variability of metallothioneins, cytochrome P450, Bile metabolites and
      oxyradical metabolism in the European eel Anguilla anguilla L. (Anguillidae) and
      striped mullet Mugil cephalus L. (Mugilidae).
AB  - The European eel Anguilla anguilla (Anguillidae) and the striped mullet Mugil
      cephalus (Mugilidae) are typical inhabitants of Mediterranean brackish lagoons,
      and their utility as bioindicator organisms has already been suggested. The
      seasonal variability of several potential biomarkers was investigated during a
      field study carried out in the Orbetello lagoon (Tuscany, Italy). Organisms were
      sampled on a seasonal basis, and analyzed parameters included the levels of
      hepatic metallothioneins, the activity of cytochrome P450 1A (EROD), and the
      presence of biliary PAH metabolites. Special attention was also paid to
      antioxidant defenses, including catalase, glutathione peroxidases, glutathione
      reductase, glutathione S-transferases, and total glutathione concentration. Total
      Oxyradical Scavenging Capacity (TOSC-assay) was measured as an indication of the
      overall biological resistance to toxicity of different forms of oxyradicals
      (peroxynitrite, peroxyl and hydroxyl radicals). Obtained results suggest that
      natural variations of analyzed responses are associated with seasonality of both
      environmental and biological factors, mainly temperature and reproductive cycle
      which, however, have a different influence in these two species. Striped mullets
      exhibited the strongest variations in October when spawning occurs; eels are not
      influenced by a seasonal sexual maturation and showed more marked changes during
      the summer, likely related to the elevated seawater temperature and light
      irradiance in the lagoon. This study confirms the importance of characterizing
      seasonal variations and the influence of different factors on biological
      responses that can be used as biomarkers in monitoring programs.

PMID- 15942814
TI  - Inflammation 2001--fifth world congress.

PMID- 15942812
TI  - Assessment of cyclin D1 overexpression as a prognostic factor in soft tissue
      sarcomas: role of laparoscopy and core needle biopsy.
AB  - BACKGROUND: This study was designed to test cyclin D1 as a prognostic marker in
      patients with soft tissue sarcomas (STS), and to evaluate the usefulness of
      laparoscopy for determining cyclin D1 overexpression. METHODS: The records of 62
      patients with STS were collected: 28 with retroperitoneal STS (RSTS) and 34 with
      extremity STS (ESTS). A total of 51 patients underwent surgical resection,
      whereas 11 did not undergo surgery because of advanced tumor stage. Preoperative
      intraoperative laparoscopic staging was performed for patients judged to be
      resectable at preoperative imaging. RESULTS: Cyclin D1 was overexpressed in 30
      (58.8%) of 51 resected patients and in 10 (90.9%) of 11 nonresected patients.
      Laparoscopy avoided unnecessary laparotomy in 9 (32.1%) of 28 RSTS patients.
      CONCLUSIONS: High tumor grade, positive surgical margins, local recurrence,
      distant metastases, and cyclin D1 overexpression were related to poor survival.
      Multivariate analysis demonstrated cyclin D1 to be the only independent factor.
      Laparoscopy was shown to be useful for avoiding useless laparotomies.

PMID- 15942815
TI  - Inflammation 2001--fifth world congress. Chronic obstructive pulmonary disease.

PMID- 15942816
TI  - COPD--fourth annual conference. Management and new avenues of research.

PMID- 15942817
TI  - BioPartnering Europe 2001--ninth annual conference.

PMID- 15942818
TI  - BioPartnering Europe 2001--ninth annual conference. Company presentations.

PMID- 15942820
TI  - British Pharmaceutical Society--138th annual conference. Controlled release
      technologies for infectious diseases.

PMID- 15942819
TI  - BioPartnering Europe 2001--ninth annual conference. Current pipelines and future
      trends.

PMID- 15942821
TI  - British Pharmaceutical Society--138th annual conference. Novel leads to the
      treatment of cancer.

PMID- 15942822
TI  - Business and science of proteomics--third annual event. Next-generation
      technologies for high-throughput proteomics.

PMID- 15942823
TI  - Royal Society of Edinburgh conference. Carbohydrates in disease: targets for
      therapies?

PMID- 15942824
TI  - Ageing and dementia: current and future concepts.

PMID- 15942825
TI  - International Xenotransplantation Association--sixth congress. Meeting the
      challenge of the new millennium.
AB  - The Sixth Congress of the International Xenotransplantion Association was a
      relatively small meeting, dealing with the most recent updates in this
      specialized field. The meeting covered all aspects of xenotransplantation,
      including physiological incompatibilities between donor animals and humans,
      genetic manipulation of pigs, immune biology of xenograft rejection, novel
      therapeutic agents, infectious risks, and ethics. It is clear that further gene
      manipulations within the potential pig donor are required before clinical trials
      involving the transplantation of most organs and tissues can commence. The
      overall impression was that of sustained progress in most areas, rather than any
      outstanding breakthroughs. On the other hand, there was no unexpected finding
      that would suggest that ultimately xenotransplantation is not feasible. New
      therapeutic agents with potential in future clinical trials were presented. In
      particular, the use of conjugates of galactose alpha-1,3 galactose (alpha-Gal),
      which are particularly effective in absorbing alpha-Gal antibodies, may be
      beneficial when pig organs progress to clinical trials.

PMID- 15942826
TI  - Genome medicine: gene therapy for the new millennium.

PMID- 15942827
TI  - Retroviral nucleocapsid--third international symposium.

PMID- 15942828
TI  - Progress in the field of selective COX-2 inhibitors--William Harvey Research
      Conference.

PMID- 15942829
TI  - European Society of Intensive Care Medicine--14th annual congress.
AB  - The European Society of Intensive Care Medicine (ESICM) annual congress provided
      an opportunity for basic scientists and clinicians to share recent findings. In
      addition to the numerous free communications, several sessions by established
      speakers were dedicated to state-of-the-art tutorials. As usual, the areas of
      interest varied widely, reflecting the large array of 'critical illnesses'.
      Results of clinical trials and experimental findings with recently developed
      drugs were presented, essentially in the fields of inflammation, sepsis and acute
      lung injury. It is evident that the benefits of several new compounds observed
      experimentally need to be confirmed in the clinic. The ESICM congress is a unique
      opportunity to implement and promote collaborations between European basic
      scientists and clinicians.

PMID- 15942830
TI  - APL and differentiation therapy--joint international congress.
AB  - This meeting formed part of a series of bi-annual conferences, which had its
      beginnings in Sardinia in 1985, with the goal of promoting the concept of
      differentiation induction in cancer therapy. As in the past, the organizers of
      this meeting aimed to bring together both basic and clinical investigators to
      promote their interaction. Therapeutic successes of all trans-retinoic acid
      (ATRA), arsenic trioxide and STI-571 have proven the importance of oncogene
      targeted therapies in cancer treatment, and underlie the usefulness of such
      interactions for effective and rational design of therapeutic approaches to
      combat malignant diseases. Consequently, discussions devoted to the clinical use
      of the above drugs, as well as to the molecular pathogeneses of the diseases in
      which these drugs are effective, occupied a considerable part of the congress.
      Although the clinical application of differentiation therapy still remains
      confined to acute promyelocytic leukemia (APL), some interesting data have began
      to emerge in other cancers where agents, such as arsenic trioxide, retinoids and
      ligands for other nuclear receptors, are showing some promise.

PMID- 15942831
TI  - Peptide--Fourth Australian Conference. From discovery to therapeutics--the new
      millennium.
AB  - The Fourth Australian Peptide Conference continued the successful trend of the
      three previous conferences and encapsulated a range of peptide studies. As well
      as describing studies on the discovery, characterization and potential
      pharmaceutical applications of peptides, the meeting also featured a significant
      emphasis on new technologies, with proteomics and mass spectrometry having
      particular prominence. Several talks described peptides that have entered or are
      about to enter clinical trials. In his welcoming comments, the chair of the
      organizing committee, Milton Hearn (Monash University, Australia) noted that
      "peptide science and its attendant disciplines will play an ever increasing role
      in all fields of the life sciences and biotechnology". The breadth of disciplines
      represented at the conference reflected this increasing role.

PMID- 15942832
TI  - Common ground in therapy of substance abuse.
AB  - Literature concerning the treatment and basis of substance abuse includes large
      contributions from clinicians and psychologists. Reviews of pharmacotherapies for
      substance abuse usually classify therapies on a clinical or behavioral basis and
      this is often complicated by the variety of abused substances and the multiple
      uses to which individual therapies are put. In contrast, this review looks at
      products from a pharmacological perspective and identifies common ground evident
      in pharmacotherapies for all substance abuse. A simple working framework for
      classifying approaches to drug development is suggested, and four distinct
      pharmacological approaches applicable both to established and potential products
      are identified.

PMID- 15942833
TI  - Fibrosis--a review of recent patent literature.
AB  - This review covers recent patent literature for fibrosis for the period 1996 to
      2001. Fibrosis related-diseases remain the number one killer in the world,
      accounting for more than 45% of entire mortality, but there are currently no
      adequate therapies for most fibrotic conditions. In recent years, however,
      antifibrotic therapeutics have rapidly progressed following the re-investigation
      of existing agents that are biologically relevant to the course of fibrosis, the
      discovery of new targets and the reinstitution of old validated targets. The
      rapid progress in assay development, recombinant protein production and
      combinatorial chemistry has allowed more new antifibrotic agents to emerge.

PMID- 15942834
TI  - Darusentan (Abbott Laboratories).
AB  - Abbott (formerly Knoll) is developing darusentan, an endothelin A antagonist, as
      a potential treatment for congestive heart failure (CHF) [398274]. The compound
      entered phase II trials in December 1998 [310187]. In a model of monocrotaline
      induced pulmonary hypertension, darusentan (50 mg/kg/day), significantly reduced
      right ventricular systolic pressure, and in a canine model of CHF chronic
      treatment for 2 weeks significantly reduced left ventricular end diastolic
      pressure, mean pulmonary artery pressure, and right atrial pressure. Darusentan
      is a selective antagonist in vitro (ET(A): K(i) = 1.4 nM; ET(B): K(i) = 184 nM)
      [339872].

PMID- 15942835
TI  - FP-21399 (Lexigen Pharmaceuticals).
AB  - Lexigen (formerly Fuji ImmunoPharmaceuticals) is developing FP-21399, a bis-azo
      compound, for the potential treatment of HIV infections. By March 1998, a phase
      II clinical study had been initiated to explore the immunologic and virologic
      activity of the compound. In the phase II study, the compound was being
      administered once a month for 48 weeks to 40 patients who are failing on protease
      inhibitor regimens either alone or with the antiretrovirals currently being taken
      by the patients. In a previous phase II study conducted by the company,
      researchers observed hints of a cellular immune response in a small subset of
      subjects at risk for disease progression or development of opportunistic
      infections [310177]. Phase I clinical trials commenced in the US in 1995
      [178794]. In a small 21-patient phase I dose escalation trial of intravenous FP
      21399, 13 patients with baseline CD4 cell counts between 50 and 400 received
      infusions of various doses (1,2 or 3 mg/kg) of the compound once a week for four
      weeks. The compound was well-tolerated and 9 patients showed an increase in CD4
      count of at least 15% over their baseline values, 2 showed a decrease in viral
      load of 1 log (90%), and 2 went from low viral loads to below the limit of
      quantification [310771,310177]. FP-21399 has been reported to interfere with the
      ability of the HIV envelope glycoproteins to use CXCR4 and CCR5 as co-receptors
      when entering CD4 cells. It concentrates in the lymph nodes, which are important
      viral reservoirs. In addition, the drug has demonstrated antiviral activity
      against many clinical and laboratory strains of HIV, including those that are AZT
      resistant [310177]. FP-21399 was selected via a screening program of Fuji's
      compounds developed originally for photographic use. It has been demonstrated, in
      preclinical studies, that FP-21399 inhibits HIV entry to the target cell by
      interfering with the V3 loop of the viral envelope. The compound has the
      advantage that it has lower toxicity than reverse transcriptase inhibitors
      because it does not enter the cells [178794].

PMID- 15942836
TI  - [Drug information for patients -- unmet needs, evaluation and influence on the
      compliance].
AB  - BACKGROUND: Many German patients are only insufficiently informed on their own
      drug therapy. Therefore, they have unmet drug information needs. We report the
      three-year experiences with the first drug information service for patients in
      Germany. We evaluate the impact of the advice on outcomes, patient sovereignty
      and Compliance. METHODS: All inquiries to the project within 36 months were
      analysed. Every patient calling within the first 24 months got a questionnaire
      for evaluation after the advice. The data were documented and analysed using a
      relational database. RESULTS: We registered 3316 inquiries. 66.2 % of the callers
      were female and 33,8 % male. The majority (64.5 %) was older than 65 years. The
      questions were mainly related to adverse drug reactions and interactions (26.6 %)
      as well as to information on efficacy of specific therapies (27.2 %). In 81,0 %
      of the patients, uncertainties regarding their medication were reduced by the
      advice. 37,9 % of the callers discussed the advice with their physician and 18,3
      % reported a decreased consultation frequency after the advice. The patient
      physician-relationship was mainly unaffected after using the service. A better
      compliance was reported by more than the half of the callers affected by non
      compliance at the time of the advice. CONCLUSIONS: The drug information service
      for patients is effective in providing medical expert information to the patients
      regarding their own medication. Additionally, the interaction competence of the
      patients was strengthened. We observed a general drug information deficit. A
      qualified advice may reduce medical problems caused by information deficits and
      reduce the use of ambulatory care. At the individual patient, the trust in its
      pharmacotherapy was strengthened and the compliance improved.

PMID- 15942837
TI  - [The lethal ingestion of cigarettes in adults: does it really exist?].
AB  - HISTORY AND ADMISSION FINDINGS: A 35-year old patient suffering from a borderline
      personality disorder was admitted to our clinic with ingestions of cigarettes
      seven times within 15 months. The patient showed symptoms of a nicotine
      intoxication with agitation, hypertension, tachycardia, dizziness and nausea
      after ingestion of 7 up to 20 cigarettes. DIAGNOSIS: Mild nicotine intoxication.
      TREATMENT AND COURSE: After therapy with gastric lavages, activated charcoals and
      saline cathartics forced acid diuresis were performed in all seven cases of
      intoxication. All courses were without complications and unit every time the
      patient could be transferred to the psychiatry within 24 hours after the
      hospitalization in our clinic. CONCLUSION: An ingestion of more than 6 cigarettes
      is considered a life-threatening intoxication for adult persons. In spite of the
      ingestion of 7 up to 20 cigarettes our patient never showed any symptoms of a
      severe or life-threatening nicotine intoxication. In the last decades no lethal
      nicotine intoxication after ingestion of cigarettes in adults was published in
      the literature.

PMID- 15942838
TI  - [A young diabetic with small-nodule liver cirrhosis, high transferrin saturation
      and negative HFE test].
AB  - HISTORY: A 28 year young female presented to our hospital for further evaluation
      with recently diagnosed diabetes mellitus, hyperpigmentation of the skin, hepato-
      and splenomegaly, thrombocytopenia and an elevated transferrin saturation (96 %),
      but a negative test for HFE gene mutations such as C282Y and H63D. FINDINGS:
      Using the mini-laparascopic technique we diagnosed a smallnodular liver cirrhosis
      with an iron overload. DIAGNOSIS AND TREATMENT: This is the clinical presentation
      of one subtype of the so called Non-HFE-hemochromatosis, the juvenile
      hemochromatosis (HFE2). Other causes of primary and secondary iron overload have
      been ruled out. Different from the HFE-positive hemochromatosis (HFE 1) in which
      the gene defect is located on chromosome 6, the defect in HFE 2 is located on
      chromosome 1. The underlying genetic defect has been localized within recently
      identified HJV gene. Phlebotomy is the treatment of choice, to be performed until
      the ferritin level is lower than 50 microg/l. CONCLUSIONS: If liver cirrhosis is
      present in hemochromatosis, the overall risk of developing heptatocellular
      carcinoma is 20 times higher than in the normal population. Therefore it is
      suggested to perform an ultrasound examination of the liver and an AFP-test every
      6 months, whereas an MRI-scan should be performed once a year, as a basis for
      further treatment options.

PMID- 15942839
TI  - [Ivabradine -- a novel approach for heart rate lowering].

PMID- 15942840
TI  - [Current diagnostics and therapy of the overactive bladder and urge
      incontinence].
AB  - Urinary incontinence affects millions of people worldwide and also represents a
      social problem. Costs of urinary incontinence and overactive bladder are very
      high. Urge incontinence is the involuntary loss of urine associated with a strong
      desire or urge to urinate. There are two types of urge incontinence: One is
      associated with involuntary detrusor contractions leading to a loss of urine, the
      other is characterized by a hypersensitive bladder in which micturition reflexes
      are induced due to an increased afferent activity. It is important to distinguish
      between an idiopathic type of urge incontinence and a symptomatic type possibly
      caused by infections, tumours, bladder stones or foreign bodies. Diagnostics is
      based on a careful medical history, clinical examination and urodynamic
      evaluation. The use of a voiding diary is necessary. Current agents for drug
      therapy rely upon their anticholinergic properties. Their use is limited by side
      effects such as blurred vision, dizziness, constipation and dryness of the mouth.
      Additionally, patients refractory to anticholinergic medication can be treated by
      endoscopic direct injection of botulinum toxin into the detrusor muscle. These
      patients can also be treated by intravesical application of vanilloid derivatives
      in the bladder leading to a desensitization of bladder sensory fibers. In some
      cases of refractory urge incontinence, electrical neuromodulation is effective.
      Other pharmacological approaches could be selective b-adrenoceptor agonists,
      calcium antagonists and potassium channel openers, but these substances are not
      yet available for clinical use.

PMID- 15942841
TI  - [The effect of haemoglobin levels on prognosis and quality of life of patients
      with bronchial carcinoma].
AB  - As a consequence of tumour and therapy related effects anaemia is a particularly
      frequent occurrence in patients with lung cancer. The ensuing symptoms such as
      dyspnoea, fatigue and decreased general health reduce their quality of life and
      can impede if not altogether prevent an effective cytostatic therapy. A positive
      outcome after oxygen-dependent anti-tumour therapy, for example radiation therapy
      or various cytostatic treatments as well, can be reduced or even put at risk when
      tumour tissue is hypoxic. In order to treat anaemia, recombinant human
      erythropoietin can be used beside blood transfusions. Erythropoietins are well
      tolerated and allow for a long-lasting, gradual increase of Hb-levels, which
      cannot be achieved via transfusions. Furthermore, transfusion risks such as
      intolerance reactions or disease transmission can also be avoided. The various
      studies presented here evaluated the impact of anaemia treatment with
      erythropoietins on the need for transfusions and quality of life of patients with
      lung cancer over the last few years. They all agreed in their conclusion that
      both parameters can be improved with erythropoietin therapy. It turned out that
      the patients' quality of life improved most when Hb levels reached around 12 g/dl
      . Studies examining the impact of anaemia treatment on a patient's prognosis also
      showed positive effects in the majority of cases. In order to investigate this
      issue, our Heidelberg work group has designed a prospective, randomised phase-III
      study on NSCLC patients, which will be explained in detail further down.

PMID- 15942842
TI  - [Personal responsibility -- a criterion for allocation in health care?].
AB  - Personal responsibility of patients for their own health is often cited as a
      means of allocating health care resources. It is however unclear whether applying
      responsibility as a distributive criterion is just. Several difficulties are
      associated with the concept of personal responsibility in the medical field.
      These include in particular 1) theoretical considerations of justice 2) causal
      factors in medicine, and 3) freedom of health behaviour. The article investigates
      these problems and tries to determine conditions for a fair use of self
      responsibility as a criterion for allocation of resources in health care.

PMID- 15942843
TI  - [Do medical consultations share in liquidation proceeds of the chief physician-
      decision of the Lower Saxony Medical Profession Court 17 November 2004--BG
      17/02].

PMID- 15942844
TI  - [Folic acid in hyperhomocysteinemia?].

PMID- 15942845
TI  - [May the family physician be informed about unapproved inpatient treatment?].

PMID- 15942848
TI  - [Gastrointestinal hemorrhages with low dosage acetylsalicylic acid].

PMID- 15942849
TI  - [[Acupuncture: what is the outcome of the Gerac Studies?--comment on DMW 4/2005].

PMID- 15942850
TI  - [Monitored anaesthesia care -- a cinderella of anaesthesiology?].

PMID- 15942851
TI  - [Complications due to patient positioning: anaesthesiological considerations].
AB  - Anaesthetist and surgeon cooperate in positioning the patient for surgery
      according to interdisciplinary agreements. The legal demands on documentation for
      standard positioning procedures are met with a symbol or short notice on the
      anaesthesia protocol. In the case of damage to the patient, however, the doctor
      has to furnish evidence that the patient has been positioned correctly.
      Complications associated with perioperative patient positioning are reported to
      be 1 to 1000. Peripheral nerves are at highest risk, but soft tissue, joint,
      vascular and ocular damages are also reported. The problems and adequate care of
      different positioning modes, such as recumbent, lateral, prone, seated and
      lithotomy position, are discussed in detail.

PMID- 15942852
TI  - [Frequency of intervention and risk factors in monitored anesthesia care in
      ophthalmic surgery -- a retrospective analysis].
AB  - BACKGROUND: Patients for ophthalmic surgery have an average age of 70 - 75 years
      and frequently suffer from cardiopulmonary disease. Despite the fact that only
      local anesthesia is applied, these patients often receive monitored anesthesia
      care. Aims of this study were to determine the frequency of drug interventions
      during monitored anesthesia care and to identify risk factors for treatment.
      PATIENTS AND METHODS: In a retrospective study, preoperative history and
      anaesthetic records of 404 patients who had received monitored anesthesia care in
      a university hospital were analyzed for patient data, preoperative diagnoses and
      intraoperative anesthesiological interventions. RESULTS: Patients were 70 +/- 12
      years old and had a high co-morbidity (63 % ASA-classification 3), especially an
      increased cardiopulmonary risk. 50 % of all patients received a drug
      intervention. 41 % were given an antihypertonic agent intraoperatively and 17 %
      received other forms of drug treatment (e. g. insulin therapy, infusion of
      electrolytes, antiemetics). In 2,5 % of the cases severe cardiovascular
      complications occurred which needed treatment (severe arrhythmias, hypertensive
      crisis, severe hypotension with need for catecholamine therapy). The two
      parameters "arterial hypertension" (54 % intervention frequency vs. 35 % without
      arterial hypertension) and the surgical procedure of "pars plana vitrectomy" (58
      % intervention frequency vs. 41 % for cataract surgery) were associated with a
      significantly increased frequency for intraoperative interventions. CONCLUSIONS:
      The high intervention frequency for a variety of complications, especially of
      cardiovascular nature, advises the presence of a physician during ophthalmic
      operations who is trained to control such emergency situations.

PMID- 15942853
TI  - [Evaluation of sympathicolysis after continuous brachial plexus analgesia using
      laser Doppler flowmetry in patients suffering from CRPS I].
AB  - OBJECTIVE: The aim of this study was to evaluate continuous brachial plexus
      analgesia in terms of pain relief and sympathicolysis in patients suffering from
      CRPS I. METHODS: A detailed clinical examination comprised measurement of
      temperature changes (Infrared Thermometry), pain rating (VAS scale) and
      assessment of peripheral sympathetic nervous function using laser Doppler
      flowmetry. A total number of 12 patients (mean age: 56 +/- 9 years, range: 30 to
      69 years) received continuous brachial plexus analgesia after placing a catheter
      in the perineurial sheath of the brachial plexus through an axillary approach.
      Prior to continuous analgesia (Morphin 0.04 mg/ml, Clonidin 1.5 microg/ml,
      Bupivacaine 0.0625 %) running at 4 ml/h a test dosis of 20 ml Bupivacaine 0.25 %
      was applied to establish brachial plexus block. RESULTS: After an equilibration
      period of 2 hours, consecutive pain measurements revealed sufficient pain relief
      in 9 out of 12 patients (75 %) with a mean pain rating dropping from 4.7 +/- 0.68
      to 1.59 +/- 1.02 (p < 0.001). Pain reduction was accompanied by a significant
      temperature increase from -0.78 degrees C to 1.7 degrees C (p < 0.05). However
      measurement of sympathetic function by laser Doppler flowmetry revealed that no
      significant sympathicolysis occurred. CONCLUSIONS: The study shows that clinical
      investigation of temperature change is not reliable in the evaluation of
      sympathicolysis. This is of special interest in patients who are suspected of
      having sympathically maintained pain (SMP) and are treated by brachial plexus
      analgesia.

PMID- 15942854
TI  - [Routine use of high inspired oxygen concentration -- pro].

PMID- 15942855
TI  - [Routine use of high inspired oxygen concentration -- con].

PMID- 15942856
TI  - [Brain natriuretic peptide for postoperative monitoring of the fluid balance in a
      cardiac surgery patient].
AB  - Brain natriuretic peptide is a neurohormone used for estimation of left
      ventricular wall tension and volume overload. We describe the use of this
      parameter in a postoperative cardiac surgery patient for detection and monitoring
      of left ventricular failure in a postoperative intensive care unit at a tertiary
      care center. Left ventricular failure was detected by brain natriuretic peptide
      levels, while x-ray and values obtained by the pulmonary artery catheter were
      inconclusive.

PMID- 15942857
TI  - [End of life decisions in intensive care].

PMID- 15942860
TI  - [Prevention of Alzheimer's disease].

PMID- 15942861
TI  - [Alzheimer's disease versus vascular dementia -- dichotomy or interaction?].
AB  - Alzheimer's dementia (AD) and vascular dementia (VD) are the two major forms of
      dementia in the elderly. They have been separated categorically on the basis of
      pathophysiological findings and clinical operationalized criteria. However, this
      strict separation has to be reevaluated in the light of recent data. The risk to
      develop a neurodegenerative dementia in old age is determined by various
      susceptibility genes and correlated with aging. In AD, the current understanding
      of pathophysiology focuses on the amyloid cascade hypothesis as the major
      endpoint of the complex cellular pathology. In VD, incomplete microangiopathic
      infarcts due to fibrohyalinosis are regarded as the major pathophysiological
      event. A controversial discussion exists about the coincidence or interaction of
      genetically determined risk factors of AD and/or VD. Further interactions between
      AD and VD exist with regard to perivascular mediators and those factors which
      impair cerebral blood flow. Based on these and other recent neuropathological and
      therapeutic findings the hypothesis is proposed that the two specific
      etiopathologies of AD and VD interact to precipitate clinical dementia in the
      individual and that the individual phenomenology of these dementias is modified
      by vascular risk factors. Neither, a categorical separation of AD and VD nor the
      recent idea to regard AD as a distinct form of vascular dementia, do appear
      convincing.

PMID- 15942862
TI  - [Awareness of memory deficits in patients with probable Alzheimer's disease].
AB  - Thirty-eight patients with Alzheimer's disease were asked to give a qualitative
      (estimation of memory changes) and quantitative assessment of their own
      performance on memory tasks and also of their relatives' performance. Qualitative
      assessment showed to be independent from measured memory-deficits, while the
      precision of quantitative prediction of performance deteriorated with increased
      cognitive impairment. Cognitive impairment of the demented patients did not
      influence the prediction of the performance of their relatives. Both, qualitative
      and quantitative assessment of memory performance were influenced by premorbid
      coping-strategies. Patients, who were attributed to use strategies of cognitive
      avoidance, more often claimed to have no changes in memory function or over
      estimated their memory performance. The results of this investigation reveal that
      methodological issues influence studies on the association of meta-cognitive
      abilities with the severity of dementia to a great extent. They also suggest that
      awareness of deficits should be based on a complex, multi-dimensional concept.

PMID- 15942863
TI  - [Neurocognitive changes and negative symptoms in schizophrenia].
AB  - It is widely recognized that schizophrenic disorders are often associated with
      impairments of cognitive performance. More recently, disorders of higher
      cognitive control processes ("executive control functions") have captured the
      attention of researchers as they can considerably impair patients' abilities to
      live an independent life. Apart from that, considering the heterogeneity of
      schizophrenia, there have been attempts to relate psychopathological syndromes to
      changes in distinct cognitive domains. The present review selectively focuses on
      evidence associating negative symptoms in schizophrenia with deficient
      performance in specific executive domains. Neurobiological evidence points to
      biochemical, structural and functional abnormalities in the frontal cortex and
      associated fronto-subcortical circuits as a common basis of both schizophrenic
      negative symptoms and disorders of executive control. In a multitude of
      neuropsychological studies, an association between negative symptoms and problems
      in the domains of response inhibition, multitasking, cognitive flexibility,
      contextual updating, problem solving and verbal fluency has been reported. In
      some cases, however, the disorganization syndrome but not the negative syndrome
      has been linked with impaired behaviour in these domains. The inconsistencies
      might be partly due to the unsatisfactory differentiation between the two symptom
      complexes. Future research should furthermore consider a more precise
      differentiation between primary and secondary negative symptoms. Finally, the
      assessment of executive control functions should be both specific and
      ecologically valid.

PMID- 15942864
TI  - [Bipolar affective and schizoaffective disorders of older age -- classification,
      symptoms and course].
AB  - Bipolar affective and schizoaffective disorders of older age are underdiagnosed,
      although they are of growing importance for psychiatric services. In this review
      article, we present and discuss results concerning classification,
      psychopathology, epidemiology, course, prognosis, neuroimaging, family studies
      and therapy. Bipolar (schizo)affective disorders of older age are a diagnostic
      heterogeneous group, especially as secondary manias must be separated from
      "endogenous" bipolar disorders nosologically. Bipolar (schizo)affective disorders
      of older age show some peculiarities: Gender ratio, age at onset, mortality and
      comorbidity with neurological disease are amongst them. Nevertheless, in many
      other aspects bipolar (schizo)affective disorders of older age do not differ from
      bipolar disorders of younger patients. For the acute and maintenance treatment
      there is a dearth of controlled studies. Lithium is of great importance. Other
      substances, as well as psychoeducation and ECT may be used analogously as in
      younger patients, if age specific factors are taken into account (as for example
      the danger of falls).

PMID- 15942865
TI  - [Syncope].

PMID- 15942866
TI  - In vitro and in vivo sulfate reduction in the gut contents of the termite
      Mastotermes darwiniensis and the rose-chafer Pachnoda marginata.
AB  - Sulfate-reducing bacteria (SRB) from termites have been assigned to the genus
      Desulfovibrio. Desulfovibrio intestinalis lives in the gut of the Australian
      termite Mastotermes darwiniensis. For the first time we were able to enrich and
      identify a sulfate-reducing bacterium from the gut of the rose-chafer Pachnoda
      marginata, which showed the highest 16S rDNA sequence identity (93%) to
      Desulfovibrio intestinalis and Desulfovibrio strain STL1. Compared to Mastotermes
      darwiniensis (1x10(7) cells of SRB per ml gut contents), sulfate-reducing
      bacteria occurred in higher numbers in the gut contents of Pachnoda marginata
      reaching cell titers of up to 2x10(8) cells per ml gut contents. In vitro sulfate
      reduction rates were determined with SRB from the gut contents of the termite
      Mastotermes darwiniensis and the beetle Pachnoda marginata. Due to the higher
      cell titer, the sulfate reduction rate of Pachnoda marginata was 10(4) nmolxh
      1xml-1 and therefore, 21 times higher than that of Mastotermes darwiniensis. In
      addition, we detected in vivo sulfate reduction in Mastotermes darwiniensis,
      which indicates that sulfate reducers play an active role in the sulfur
      metabolism in the termite gut.

PMID- 15942867
TI  - Pseudomonas xanthomarina sp. nov., a novel bacterium isolated from marine
      ascidian.
AB  - Two Pseudomonas-like yellow-orange-pigmented non-fluorescent denitrifying strains
      KMM 235 and KMM 1447T were isolated from marine ascidian specimens and
      investigated by a polyphasic approach to clarify their taxonomic status. On the
      basis of 16S rDNA gene sequence data the new isolates clustered with the
      Pseudomonas stutzeri species group with sequence similarities of >98%. The
      results of DNA-DNA hybridization and biochemical characterization showed genetic
      and phenotypic distinction between strains KMM 235 and KMM 1447T and from the
      other validly described Pseudomonas species. Strain KMM 235 was found to be
      closely related to the type strain of Pseudomonas stutzeri in their phenotypic
      and genetic characteristics and represented, probably, a new P. stutzeri
      genomovar. It is proposed that strain KMM 1447T be classified as a new species of
      the genus Pseudomonas, Pseudomonas xanthomarina sp. nov., with the type strain
      KMM 1447T (=JCM 12468T=NRIC 0617T=CCUG 46543T).

PMID- 15942868
TI  - Isolation of Saccharomyces cerevisiae RNase T1 hypersensitive (rns) mutants and
      genetic analysis of the RNS1/DSL1 gene.
AB  - Overexpression of the rntA cDNA encoding RNase T1 derived from A. oryzae causes
      severe growth inhibition in S. cerevisiae. We previously reported that most S.
      cerevisiae mutant strains defective in translocation into the ER, ER-Golgi
      transport and vacuole formation exhibited hypersensitivity to expression of RNase
      T1. Screening for S. cerevisiae mutants that showed RNase T1 hypersensitivity
      resulted in the isolation of 38 (rns) mutant strains. Some of these mutants
      showed a variety of phenotypes including temperature-sensitive growth,
      hypersensitivity to G418, defect in invertase glycosylation and fragmented
      vacuoles. We identified the genes mutated in three of the rns mutants, rns1,
      rns2, and rns3, as DSL1, UMP1, and SEC17, respectively. Fluorescence microscopic
      observation showed that GFP or myc-tagged Rns1p was localized at the nuclear
      region in the cell. Two-hybrid screening revealed the interaction of Rns1p with a
      transcription factor Cin5p and a functionally unknown Ylr440cp. It was observed
      that HA-tagged Ylr440cp was localized to the ER and nuclear envelope.

PMID- 15942869
TI  - Screening of yeasts as probiotic based on capacities to colonize the
      gastrointestinal tract and to protect against enteropathogen challenge in mice.
AB  - Probiotics are defined as viable microorganisms that exhibit a beneficial effect
      on the host's health when they are ingested. Two important criteria are used for
      selection of probiotic microorganisms: they must be able to survive in the
      gastrointestinal environment and to present at least one beneficial function
      (colonization resistance, immunomodulation or nutritional contribution).
      Generally, in vitro assays demonstrating these properties were used to select
      probiotics but it is unclear if the data can be extrapolated to in vivo
      conditions. In the present work, twelve Saccharomyces cerevisiae strains isolated
      from different environments (insect association, tropical fruit, cheese and
      "aguardente" production) and pre-selected for in vitro resistance to simulated
      gastrointestinal conditions were inoculated in germ-free mice to evaluate their
      real capacity to colonize the mammal digestive tract. Using these data, one of
      the yeasts (S. cerevisiae 905) was selected and tested in gnotobiotic (GN) and
      conventional (CV) mice for its capacity to protect against oral challenge with
      two enteropathogenic bacteria (Salmonella Typhimurium and Clostridium difficile).
      The yeast reached populational levels potentially functional in the
      gastrointestinal portions where the enteropathogens tested act. No antagonism
      against either pathogenic bacterium by the yeast was observed in the digestive
      tract of GN mice but, after challenge with S. Typhimurium, mortality was lower
      and liver tissue was better preserved in CV animals treated with the yeast when
      compared with a control group (p<0.05). Histopathological results of intestines
      showed that the yeast also presented a good protective effect against oral
      challenge with C. difficile in GN mice (p<0.05). In conclusion, among the 12 S.
      cerevisiae tested, strain 905 showed the best characteristics to be used as a
      probiotic as demonstrated by survival capacity in the gastrointestinal tract and
      protective effect of animals during experimental infections.

PMID- 15942870
TI  - Analysis of reading frame and expressional regulation of randomly selected
      promoter-proximal genes in Escherichia coli.
AB  - The expression of seventy-seven randomly cloned genes of Escherichia coli was
      examined following a variety of treatments including heat shock, glucose
      starvation, phosphate starvation, ammonium starvation or osmotic shock, with the
      aid of lacZ reporter gene protein fusions on multicopy plasmids. Two of 77 genes
      (amr and yigL) had not previously been identified as protein encoding open
      reading frames (ORFs) in annotations of the E. coli genome database. Thirteen
      genes exhibited significant changes in expression in response to at least one of
      the treatments, and six of them appeared to be controlled by more than one sigma
      (sigma) factor of RNA polymerase. This study thus allows us not only to identify
      the reading frame of the genomic genes but also to support the hypothesis earlier
      proposed that a significant proportion of genes in E. coli are involved in
      adaptations to various stresses to which the organism is likely to be exposed in
      the environment.

PMID- 15942871
TI  - A new strain of Butyrivibrio fibrisolvens that has high ability to isomerize
      linoleic acid to conjugated linoleic acid.
AB  - A new strain of Butyrivibrio fibrisolvens (TH1) that has high potential to
      produce conjugated linoleic acid (CLA) was isolated. Strain TH1 had higher LA
      isomerase (LA-I) activity, and was much more tolerant to linoleic acid (LA) than
      other strains examined. However, high CLA reductase (CLA-R) activity resulted in
      the temporary accumulation of CLA and subsequent conversion to trans-vaccenic
      acid (t-VA). When LA was added to growing TH1 cultures in a solution with
      dimethylsulfoxide (LA/DMSO), CLA produced was greater than when LA was added in a
      mixture with bovine serum albumin (BSA). The number of viable cells decreased
      upon addition of LA/DMSO, but then increased as the CLA decreased upon its
      conversion to t-VA. This result suggests that B. fibrisolvens can resume growing
      by the removal of CLA from the cells. Most CLA was released from B. fibrisolvens
      cells by gentle washing with BSA, suggesting that CLA bound to the cells might be
      removed in the rumen and large intestine. Thus, CLA production by B. fibrisolvens
      in the digestive tract could be increased by a reduction in CLA-R activity
      without accompanying an overall decrease in the cell number of B. fibrisolvens.
      Fatty acids (FAs) with 18 carbon backbone inducted LA-I activity, whereas
      unsaturated FAs induced CLA-R activity, suggesting that FAs stimulate the
      synthesis of LA-I and CLA-R. Providing a diet with a low ratio of unsaturated to
      saturated FAs may favor CLA production.

PMID- 15942872
TI  - Growth, photosynthesis, active oxygen species and antioxidants responses of paddy
      field cyanobacterium Plectonema boryanum to endosulfan stress.
AB  - The present paper deals with the insecticide endosulfan (5, 10 and 20 microg/ml)
      induced changes in physiological and biochemical parameters related to
      photosynthesis and defense systems in paddy field cyanobacterium Plectonema
      boryanum grown under laboratory conditions. Growth and photosynthetic pigments,
      i.e., chlorophyll a, carotenoids and phycocyanin, were adversely affected by
      endosulfan treatment and the inhibition was found to be dose dependent. The toxic
      effect of endosulfan was more pronounced on phycocyanin; however, a considerable
      reduction in chlorophyll a and carotenoids was also noticed. 14C-fixation
      appeared to be more sensitive to insecticide than whole cell oxygen evolution.
      Spheroplasts treated with endosulfan exhibited a severe effect on PSII activity
      which was mainly due to blocking of the electron flow at the water oxidation
      side. In contrast to this, similar doses of endosulfan caused the least effect on
      PSI activity (DCPIP/ASC-->MV). Furthermore, endosulfan with increasing doses
      accelerated the formation of active oxygen species, i.e., O2- and H2O2, in cells
      progressively, whereby an enhanced peroxidation of lipid and leakage of cell
      membrane were noticed. As a consequence of active oxygen species (AOS) generation
      in endosulfan-treated cells, the activity of superoxide dismutase (SOD), catalase
      (CAT) and peroxidase (POD) was enhanced considerably. Besides the accelerated
      action of enzymatic defense systems, chemical antioxidant ascorbate showed a
      decreasing trend with the rising concentration of endosulfan (5, 10 and 20
      microg/ml).

PMID- 15942873
TI  - Detection and precipitation of hepatitis B core antigen using a fusion
      bacteriophage.
AB  - The nucleocapsids of hepatitis B virus (HBV) are made of 180 or 240 subunits of
      core proteins or known as core antigens (HBcAg). A fusion bacteriophage bearing
      the WSFFSNI sequence that interacts tightly to HBcAg was employed as a diagnostic
      reagent for the detection of the antigen using the phage-enzyme-linked
      immunosorbent (phage-ELISA), dot blot and immunoprecipitation assays. The results
      from phage-ELISA and dot blot assay showed that as low as 10 ng of HBcAg can be
      detected optimally by 1.0x10(12) pfu/ml fusion M13 bacteriophage. The sensitivity
      of the dot blot assay corresponds with that of the phage-ELISA. HBcAg in HBV
      positive serum samples can also be detected using the fusion phage via the phage
      ELISA and phage-dot blot assay. The phage cross-linked to cyanogen bromide (CNBr)
      activated agarose can also be used to precipitate HBcAg in bacterial lysate. The
      optimum amount of phage needed for cross-linking to 1 g of agarose is about
      7.0x10(6) pfu/ml which could also precipitate purified and unpurified HBcAg in
      bacterial lysate. This study demonstrates the potential of fusion bacteriophage
      bearing the sequence WSFFSNI as a diagnostic reagent and a ligand for the
      detection and purification of HBcAg respectively.

PMID- 15942874
TI  - Synthesis of Schiff bases of 2-amino-5-aryl-1,3,4-oxadiazoles and their
      evaluation for antimicrobial activities.
AB  - Twenty Schiff bases of 2-amino-5-aryl-1,3,4-oxadiazoles have been synthesized
      with different aromatic aldehydes. The structures of the compounds were confirmed
      by nitrogen analysis, IR and 13C-NMR spectral data. The antibacterial properties
      of the compounds were investigated against Proteus mirabilis (MTCC-425),
      Pseudomonas aeruginosa (MTCC-424), Bacillus subtilis (MTCC-619) and
      Staphylococcus aureus (MTCC-96) using the broth dilution method. The most active
      compounds were 4c (64 microg/ml), 4f (68 microg/ml), 4m (64 microg/ml) and 4q (62
      microg/ml). The antifungal screening of the compounds were carried out using
      Aspergillus niger (MTCC-1344) and Candida albicans (MTCC-227) using the broth
      dilution method. Active compounds were 4g (52 microg/ml), 4h (56 microg/ml), 4l
      (60 microg/ml), 4m (58 microg/ml).

PMID- 15942875
TI  - Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals
      with NSD1 aberrations.
AB  - We identified 266 individuals with intragenic NSD1 mutations or 5q35
      microdeletions encompassing NSD1 (referred to as "NSD1-positive individuals"),
      through analyses of 530 subjects with diverse phenotypes. Truncating NSD1
      mutations occurred throughout the gene, but pathogenic missense mutations
      occurred only in functional domains (P < 2 x 10(-16)). Sotos syndrome was
      clinically diagnosed in 99% of NSD1-positive individuals, independent of the
      molecular analyses, indicating that NSD1 aberrations are essentially specific to
      this condition. Furthermore, our data suggest that 93% of patients who have been
      clinically diagnosed with Sotos syndrome have identifiable NSD1 abnormalities, of
      which 83% are intragenic mutations and 10% are 5q35 microdeletions. We reviewed
      the clinical phenotypes of 239 NSD1-positive individuals. Facial dysmorphism,
      learning disability, and childhood overgrowth were present in 90% of the
      individuals. However, both the height and head circumference of 10% of the
      individuals were within the normal range, indicating that overgrowth is not
      obligatory for the diagnosis of Sotos syndrome. A broad spectrum of associated
      clinical features was also present, the occurrence of which was largely
      independent of genotype, since individuals with identical mutations had different
      phenotypes. We compared the phenotypes of patients with intragenic NSD1 mutations
      with those of patients with 5q35 microdeletions. Patients with microdeletions had
      less-prominent overgrowth (P = .0003) and more-severe learning disability (P = 3
      x 10(-9)) than patients with mutations. However, all features present in patients
      with microdeletions were also observed in patients with mutations, and there was
      no correlation between deletion size and the clinical phenotype, suggesting that
      the deletion of additional genes in patients with 5q35 microdeletions has little
      specific effect on phenotype. We identified only 13 familial cases. The reasons
      for the low vertical transmission rate are unclear, although familial cases were
      more likely than nonfamilial cases (P = .005) to carry missense mutations,
      suggesting that the underlying NSD1 mutational mechanism in Sotos syndrome may
      influence reproductive fitness.

PMID- 15942877
TI  - The quinolones: past, present, and future.
AB  - The quinolone class of antimicrobial agents has generated considerable interest
      since its discovery >40 years ago. Substantial progress has been made in our
      understanding of the molecular mechanisms of the action of quinolones against
      pathogenic bacteria, the induction of resistance to quinolones in these
      organisms, and the potential of each quinolone compound to induce toxicity in
      treated patients. Here, these key discoveries are reviewed; the present
      indications approved by regulatory agencies are described in detail, with
      comments on adverse events caused by quinolones in treated patients; and
      speculation about the future of the quinolones is proffered, even though their
      future is difficult to predict, because many factors may affect their clinical
      usefulness. However, the emergence of bacterial resistance to the quinolones is a
      major factor that will determine the future clinical effectiveness of these
      agents, so that intense investigation of mechanisms to either prevent or curtail
      resistance to quinolones is of prime importance to their future.

PMID- 15942878
TI  - Mechanisms of resistance to quinolones.
AB  - The increased use of fluoroquinolones has led to increasing resistance to these
      antimicrobials, with rates of resistance that vary by both organism and
      geographic region. Resistance to fluoroquinolones typically arises as a result of
      alterations in the target enzymes (DNA gyrase and topoisomerase IV) and of
      changes in drug entry and efflux. Mutations are selected first in the more
      susceptible target: DNA gyrase, in gram-negative bacteria, or topoisomerase IV,
      in gram-positive bacteria. Additional mutations in the next most susceptible
      target, as well as in genes controlling drug accumulation, augment resistance
      further, so that the most-resistant isolates have mutations in several genes.
      Resistance to quinolones can also be mediated by plasmids that produce the Qnr
      protein, which protects the quinolone targets from inhibition. Qnr plasmids have
      been found in the United States, Europe, and East Asia. Although Qnr by itself
      produces only low-level resistance, its presence facilitates the selection of
      higher-level resistance mutations, thus contributing to the alarming increase in
      resistance to quinolones.

PMID- 15942879
TI  - Clinical implications of pharmacokinetics and pharmacodynamics of
      fluoroquinolones.
AB  - This review summarizes key data illustrating the clinical importance of
      pharmacodynamics, particularly among the fluoroquinolone family of
      antibacterials. Antibacterials are often divided into 2 groups--either time
      dependent or concentration-dependent agents--on the basis of their mechanism of
      killing. Fluoroquinolones are concentration-dependent agents, and the parameter
      that correlates most closely with clinical and/or bacteriological success is the
      ratio of the area under plasma concentration curve (AUC) to the minimum
      inhibitory concentration (MIC). The AUC : MIC threshold may vary by organism. For
      example, a ratio of at least 30 is often cited as optimal to achieve success
      against Streptococcus pneumoniae, whereas higher ratios (>100) are considered to
      be optimal for the treatment of infections due to gram-negative bacilli. Data are
      cited to suggest that the minimum ratio necessary to prevent the selection of
      resistant mutants may, in fact, be somewhat higher. Maximizing the AUC : MIC
      through the use of potent therapy may offer an opportunity to limit the
      development of resistance to fluoroquinolones.

PMID- 15942880
TI  - Pharmacoeconomic considerations associated with the use of intravenous-to-oral
      moxifloxacin for community-acquired pneumonia.
AB  - BACKGROUND: Intravenous-to-oral (iv/po) conversion is one cost-effective approach
      to the management of community-acquired pneumonia (CAP). METHODS: Consecutive
      patients with CAP were enrolled during 3 study periods (January-March of 2001,
      2002, and 2004) with different pharmacy intervention (PI) strategies: iv beta 
      lactam plus a macrolide (no PI), iv beta-lactam plus a macrolide with iv/po PI
      (PI switch), and iv moxifloxacin with pharmacist-initiated automatic po
      moxifloxacin conversion (PI sequential). Costs and outcomes were compared among
      groups. RESULTS: Two hundred fifty-one patients were enrolled. The average Fine
      score was 75, and the mean age of patients was 51 years. In the PI groups, the
      duration of treatment with iv antibiotics was decreased. Clinical success on day
      3 of therapy was improved in the PI sequential group but was similar in all 3
      groups on day 7 of therapy and at the end of therapy. The length of stay in the
      hospital was similar for patients in all 3 groups (mean, 4.39 days). Antibiotic
      costs were significantly reduced, by $110/patient, in the PI sequential group.
      CONCLUSIONS: Conversion from iv to po therapy was accomplished more quickly when
      converting to the same agent with pharmacist-initiated automatic iv/po
      conversion, thus reducing the associated cost without compromising efficacy.

PMID- 15942881
TI  - Antimicrobial safety: focus on fluoroquinolones.
AB  - BACKGROUND/PURPOSE: Infrequent toxicities associated with certain drugs and drug
      classes have recently gained much attention from different health-care
      perspectives. To protect the patient, continued surveillance of safety and
      tolerability data is essential. Data from preclinical testing, phase 1-3 trials,
      and postmarketing surveillance may be used to objectively assess the risks
      associated with a specific drug or family of compounds. This review summarizes
      safety and tolerability data for the quinolones. MAIN FINDINGS: The most common
      adverse events associated with the quinolone class involve the gastrointestinal
      tract (nausea and diarrhea) and central nervous system (CNS) (headache and
      dizziness). These adverse events are usually mild and do not require
      discontinuation of therapy. Uncommon and potentially serious quinolone-related
      adverse events involve the cardiovascular system (rate-corrected
      electrocardiographic QT interval prolongation), musculoskeletal system
      (tendinitis and tendon rupture), endocrine system (glucose homeostasis
      dysregulation), renal system (crystalluria, interstitial nephritis, and acute
      renal failure), and the CNS (seizures). Severe idiosyncratic adverse events are
      specific to individual agents that may share some structural congruity, such as
      the 1-(2,4)-difluorophenyl group shared by trovafloxacin (associated with
      hepatitis), temafloxacin (associated with hemolytic-uremic syndrome), and
      tosufloxacin (associated with eosinophilic pneumonitis). Overall, discontinuation
      rates from clinical trials were <4% for the currently marketed quinolones.
      Quinolones with higher discontinuation rates, such as trovafloxacin (7.0%) and
      grepafloxacin (6.4%), are no longer available for general use. CONCLUSIONS: The
      currently marketed quinolones are well tolerated, with safety profiles similar to
      those of other antimicrobial classes. Although adverse effects are unusual, some,
      including tendinitis and CNS-related effects, are more common with quinolones
      than with other antimicrobial classes. Rare adverse effects attributed to some
      members of the quinolone family (e.g., Torsades de Pointes, hepatotoxicity, and
      dysglycemias) are more likely to occur in select "susceptible" populations. These
      adverse events can often be circumvented by avoiding exposure to the specific
      quinolone. In some cases, the therapeutic value offered by a quinolone may
      outweigh its potential risks.

PMID- 15942882
TI  - Challenges in the management of community-acquired pneumonia: the role of
      quinolones and moxifloxacin.
AB  - Current strategies and guidelines for the treatment of community-acquired
      pneumonia are directed toward making care cost effective, by treating patients on
      an outpatient basis whenever possible. The use of the new fluoroquinolones could
      help to achieve these goals. These agents are highly bioavailable and can
      facilitate the oral treatment of certain patients who otherwise might be admitted
      to the hospital, as outpatients. The good absorption and bioavailability of these
      agents can allow moderately ill patients to rapidly achieve effective serum
      levels of the drug after oral administration and can also facilitate early
      discontinuation of intravenous therapy and early discharge for responding
      inpatients. For inpatients or outpatients with clinical risk factors for
      acquiring drug-resistant pneumococci, quinolones represent a reliable monotherapy
      option and an effective alternative to a beta-lactam/macrolide combination.
      Although the in vitro differences among the various quinolones remain of unclear
      clinical relevance, preliminary data suggest that agents with enhanced in vitro
      activity against pneumococci, such as moxifloxacin, may have greater clinical
      efficacy and may lead to more-rapid resolution of fever and, potentially, less
      selection of future pneumococcal resistance to quinolones than that associated
      with agents with less intrinsic activity.

PMID- 15942883
TI  - Current management of acute bacterial rhinosinusitis and the role of
      moxifloxacin.
AB  - Episodes of acute rhinosinusitis are common among adults and are associated with
      a significant amount of morbidity. The symptoms of rhinosinusitis are nasal
      drainage, congestion, and sinus pressure. A bacterial sinus infection is more
      likely if these symptoms worsen after 5-7 days or do not improve after 10-14
      days. The majority of bacterial episodes have been associated with Streptococcus
      pneumoniae and Haemophilus influenzae. In the current era of increasing
      resistance to beta -lactams and macrolides, treatment guidelines have been
      formulated worldwide to assist clinicians in the selection of antibacterials.
      According to one model, the following antibacterials are most likely to provide
      desired outcomes (90%-92% predicted clinical efficacy) for adults: respiratory
      fluoroquinolones (i.e., moxifloxacin, gatifloxacin, and levofloxacin),
      ceftriaxone, and high-dose amoxicillin-clavulanate (4 g of amoxicillin/day and
      250 mg of clavulanate/day). Although the role of the fluoroquinolones in the
      treatment of this condition is evolving, fluoroquinolones are often recommended
      as second-line therapy or as first-line therapy for selected patients (e.g.,
      those who received antibacterials in the previous 4-6 weeks or adults with
      moderate-to-severe disease).

PMID- 15942884
TI  - Moxifloxacin for the treatment of acute exacerbations of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND/PURPOSE: The significant impact of acute exacerbations of chronic
      obstructive pulmonary disease (AECOPD) is now recognized. This recognition has
      led to increased efforts to provide evidence-based, appropriate treatment of
      AECOPD, to minimize its negative impact. This article reviews the bacterial
      etiology of AECOPD and clinical trials (both placebo-controlled and antibiotic
      comparison trials) that support the use of antibiotics for AECOPD, with an
      emphasis on the role of newer fluoroquinolones for the treatment of patients with
      this condition. A discussion of patient stratification that permits
      identification of those who require initial aggressive antibiotic therapy is
      presented. MAIN FINDINGS: Among the treatment modalities for exacerbations, the
      role and choice of antibiotics is hotly debated. Current evidence supports the
      use of antibiotics in the treatment of AECOPD, because bacterial pathogens cause
      approximately half the exacerbations, and because empirical antibiotics have a
      significant benefit in most exacerbations. Several recent investigations have
      aided in the development of a rational antibiotic strategy for AECOPD. These
      include outcome studies that have identified patients who are likely to have a
      poor outcome of their exacerbation and, therefore, are candidates for aggressive
      initial antibiotic therapy. Studies of the new fluoroquinolone agents have shown
      superior short- and long-term clinical results among patients with AECOPD who are
      at risk of a poor outcome. CONCLUSIONS: Theoretical concerns about the emergence
      of resistance to the fluoroquinolones dictate not only the appropriate use of
      these drugs but, also, the use of the most-potent agents available in this class,
      to sustain their usefulness over time. Such selected use of the new
      fluoroquinolones balances individual benefit with societal concerns regarding the
      use of these agents for the treatment of AECOPD.

PMID- 15942885
TI  - Single-dose nevirapine and drug resistance: the more you look, the more you find.

PMID- 15942886
TI  - HIV [corrected] genetic diversity surveillance in the United States.

PMID- 15942887
TI  - It is too early to discount the contribution of isoniazid to the treatment of
      tuberculous meningitis.

PMID- 15942888
TI  - Streptolysin S.

PMID- 15942889
TI  - Emergence of drug-resistant HIV-1 after intrapartum administration of single-dose
      nevirapine is substantially underestimated.
AB  - Conventional sequence analysis detects human immunodeficiency virus (HIV)-1 drug
      resistance mutations in approximately 40% of women shortly after they receive
      intrapartum single-dose nevirapine (SD-NVP). Using sensitive real-time polymerase
      chain reaction assays for the K103N and Y181C resistance mutations, we tested
      genotyped virus before and after SD-NVP in 50 South African women infected with
      HIV-1 subtype C. By sequence analysis, 40 women had no detectable resistance
      mutations, and an additional 6 women were negative for Y181C after SD-NVP. We
      found K103N in 16 (40%) of 40 women and Y181C in 5 (11%) of 46 women at 6-36
      weeks postpartum. Clonal sequencing confirmed K103N in 5 of 5 representative
      samples and Y181C in 4 of 4 samples. Four of the 5 women with newly identified
      Y181C also had K103N. These findings indicate that resistance mutations emerged
      in at least 65% of the women after SD-NVP and emphasize the importance of further
      research to determine the clinical implications.

PMID- 15942890
TI  - Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants
      with the K103N nevirapine (NVP) resistance mutation in some women and infants
      after the administration of single-dose NVP: HIVNET 012.
AB  - BACKGROUND: The HIV Network for Prevention Trials (HIVNET) 012 trial showed that
      NVP resistance (NVPR) emerged in some women and children after the administration
      of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human
      immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or
      more after the administration of SD-NVP. METHODS: We analyzed samples from 9
      women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration
      of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive
      resistance assays, LigAmp and TyHRT. RESULTS: ViroSeq detected the K103N mutation
      in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low
      levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq
      12-24 months after the administration of SD-NVP but was detected by LigAmp in 3
      of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use
      of the TyHRT assay. CONCLUSIONS: K103N-containing variants persist in some women
      and infants for 1 year or more after the administration of SD-NVP. Sensitive
      resistance assays may provide new insight into the impact of antiretroviral drug
      exposure on HIV-1 evolution.

PMID- 15942891
TI  - Nevirapine (NVP) resistance in women with HIV-1 subtype C, compared with subtypes
      A and D, after the administration of single-dose NVP.
AB  - OBJECTIVE: In the Human Immunodeficiency Virus (HIV) Network for Prevention
      Trials (HIVNET) 012 trial in Uganda, 6-8 weeks after single-dose nevirapine (SD
      NVP), NVP resistance mutations were detected at a higher rate in women with HIV-1
      subtype D than in women with subtype A. Here, we evaluate the rate of NVP
      resistance mutations in women with subtype C. METHODS: NVP resistance mutations
      were detected using the ViroSeq HIV-1 Genotyping System. RESULTS: The portion of
      women with any NVP resistance mutation was higher in those with subtype C (45/65
      [69.2%] in the NVP and zidovudine trial, Malawi) than in those in the HIVNET 012
      trial with either subtype A (28/144 [19.4%]; P<.0001) or subtype D (35/97
      [36.1%]; P<.0001). In a multivariate model, subtype (C vs. A: odds ratio [OR],
      8.73 [95% confidence interval {CI}, 4.29-17.76]; C vs. D: OR, 3.38 [95% CI, 1.65
      6.93]) and viral load at delivery (OR, 2.35 [95% CI, 1.62-3.40]) independently
      predicted NVP resistance mutations, but maternal age, parity, and time between SD
      NVP and the 6-8-week visit did not. CONCLUSIONS: The rate of NVP resistance
      mutations after SD-NVP was significantly higher in women with HIV-1 subtype C
      than in women with subtype A or D. Studies are needed to assess the clinical
      significance of this finding.

PMID- 15942892
TI  - HIV-1 subtype diversity in Minnesota.
AB  - BACKGROUND: Genetic variation in human immunodeficiency virus (HIV)-1 poses
      significant public-health and clinical challenges. In North America, subtype B is
      most prevalent. HIV-1 subtyping is not integrated into routine HIV/acquired
      immunodeficiency syndrome surveillance in the United States. In 2003, the
      Minnesota Department of Health piloted HIV-1 subtyping with routine surveillance
      to describe the existence and variety of non-subtype B strains. METHODS: Targeted
      HIV-1 subtype surveillance was conducted on 98 African-born HIV-infected
      patients. Sentinel subtype surveillance was conducted in a Minneapolis sexually
      transmitted disease clinic on 28 newly diagnosed non-African HIV-positive
      patients. Subtype determination was based on a partial sequence of the gp41
      region of the HIV-1 env gene. RESULTS: Subtyping was successful for 87 of 98
      samples from African-born HIV-infected patients; 95% were non-B subtypes. The 7
      subtypes observed were consistent with strains endemic in patients' birth
      regions. Subtyping was also completed for samples from 25 of 28 non-African-born
      patients; all were subtype B. CONCLUSIONS: Multiple HIV-1 subtypes are present in
      Minnesota. Our data suggest that most of the HIV cases in Minnesota among African
      born patients are non-B subtypes. Population-based surveillance inclusive of
      groups at high risk for variant strains is needed to monitor the prevalence and
      variety of HIV subtypes in the United States.

PMID- 15942893
TI  - Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of
      disease progression independently of HIV-1 RNA levels and CD4+ T cell counts.
AB  - BACKGROUND: The objective of this work was to assess the role of human
      immunodeficiency virus (HIV) reservoirs in the risk of disease progression, by
      studying the relationship between HIV DNA level in peripheral blood mononuclear
      cells (PBMCs) and progression toward acquired immunodeficiency syndrome (AIDS).
      METHODS: HIV-1 DNA levels in PBMCs were determined by quantitative polymerase
      chain reaction for 383 patients enrolled in the SEROCO Cohort Study who had
      experienced seroconversion and had been followed up for >8 years. We compared the
      predictive values of HIV DNA level, HIV RNA level, and CD4+ cell count. RESULTS:
      Between 6 and 24 months after seroconversion, HIV DNA level was a major predictor
      of progression to AIDS independently of HIV RNA level and CD4+ T cell count
      (adjusted relative risk [RR] for a 1-log(10) increase, 3.20 [95% confidence
      interval {CI}, 1.70-6.00]). HIV DNA level was also a major predictor of disease
      progression during the first 6 months after seroconversion (adjusted RR, 4.16
      [95% CI, 1.70-10.21]), when HIV RNA level and CD4+ T cell count were less
      predictive. Thus, a combination of these 3 markers provides the best estimate of
      the risk of disease progression for each patient. CONCLUSIONS: Our results
      suggest that HIV DNA level could be a useful additional marker in clinical
      practice and could aid in helping to define the best time to initiate treatment
      for each patient.

PMID- 15942894
TI  - Identification of attenuated variants of HIV-1 circulating recombinant form 01_AE
      that are associated with slow disease progression due to gross genetic
      alterations in the nef/long terminal repeat sequences.
AB  - We identified an unusual case of human immunodeficiency virus type 1 (HIV-1)
      infection in a patient (GM43) who exhibited a persistently low antibody response
      and undetectable viral load during a 5-year follow-up period. GM43 harbored HIV-1
      circulating recombinant form 01_AE with gross deletions in the nef/long terminal
      repeat (LTR) region. The sizes of the deletions increased progressively from 84
      to >400 bp during the 5-year period. GM43 appeared to have acquired defective
      variants from her husband. The genetic alterations in the nef/LTR region were
      remarkably similar to those that have been reported in slow progressors (such as
      the slow progressors in the Sydney Blood Bank Cohort). The present study is the
      first report of slow disease progression due to gross genetic alterations in the
      nef/LTR region in a person infected with an HIV-1 non-subtype B strain.

PMID- 15942895
TI  - Peripheral S-phase T cells in HIV disease have a central memory phenotype and
      rarely have evidence of recent T cell receptor engagement.
AB  - Heightened proliferation and death of T lymphocytes may play a key role in human
      immunodeficiency virus (HIV) pathogenesis; however, the mechanism that mediates
      this effect and the phenotype of the proliferating T cells have not been clearly
      determined. We assessed S-phase cell frequencies and phenotype by ex vivo
      bromodeoxyuridine incorporation and flow-cytometric analysis in a group of 35 HIV
      infected individuals. Frequencies of S-phase T cells were increased in HIV
      disease and were related to plasma HIV RNA levels but not to CD4 cell, total T
      cell, or total lymphocyte counts. S-phase cells were phenotypically defined as
      "central memory" cells (CD45RO+CD62L+CCR7+). Although activated (CD38+), S-phase
      cells lacked CD69 expression, rarely expressed CD25, and were not overrepresented
      among HIV-specific cells, as might have been expected if these cells had recently
      been activated by HIV antigens. Thus, in HIV infection, central memory T cells
      may be highly susceptible to bystander mechanisms of immune activation, leading
      to S-phase entry.

PMID- 15942896
TI  - Inhibition of HIV-1 replication in human lymphoid tissues ex vivo by measles
      virus.
AB  - Human immunodeficiency virus (HIV) type 1 replication and disease progression are
      enhanced by various pathogens in coinfected individuals. However, acute infection
      with measles virus (MV) has been found to suppress HIV-1 replication in
      coinfected children. We investigated the mechanisms of this phenomenon using
      human lymphoid tissues coinfected ex vivo with HIV-1 and MV. MV inhibited both
      CXCR4-tropic (X4) and CCR5-tropic (R5) HIV-1, but the inhibitory effect was
      particularly profound for R5 virus, which transmits infection and dominates the
      early stages of HIV-1 disease. MV inhibits the replication of R5 HIV-1 in
      coinfected tissues by up-regulation of the CC chemokine RANTES, a well-known
      inhibitor of R5 HIV-1 infection, and this up-regulation is augmented in tissues
      coinfected with R5 HIV-1. Deciphering the molecular mechanisms by which MV and
      other pathogens alter local cytokine/chemokine networks and cause tissue
      microenvironments to become detrimental to HIV-1 may significantly contribute to
      the development of effective anti-HIV therapies.

PMID- 15942897
TI  - Effect of antituberculosis drug resistance on response to treatment and outcome
      in adults with tuberculous meningitis.
AB  - BACKGROUND: Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis
      resistant to 1 or more antituberculosis drugs is an increasingly common clinical
      problem, although the impact on outcome is uncertain. METHODS: We performed a
      prospective study of 180 Vietnamese adults admitted consecutively for TBM. M.
      tuberculosis was cultured from the cerebrospinal fluid (CSF) of all patients and
      was tested for susceptibility to first-line antituberculosis drugs. Presenting
      clinical features, time to CSF bacterial clearance, clinical response to
      treatment, and 9-month morbidity and mortality were compared between adults
      infected with susceptible and those infected with drug-resistant organisms.
      RESULTS: Of 180 isolates, 72 (40.0%) were resistant to at least 1
      antituberculosis drug, and 10 (5.6%) were resistant to at least isoniazid and
      rifampicin. Isoniazid and/or streptomycin resistance was associated with slower
      CSF bacterial clearance but not with any differences in clinical response or
      outcome. Combined isoniazid and rifampicin resistance was strongly predictive of
      death (relative risk of death, 11.63 [95% confidence interval, 5.21-26.32]) and
      was independently associated with human immunodeficiency virus infection.
      CONCLUSIONS: Isoniazid and/or streptomycin resistance probably has no detrimental
      effect on the outcome of TBM when patients are treated with first-line
      antituberculosis drugs, but combined isoniazid and rifampicin resistance is
      strongly predictive of death.

PMID- 15942898
TI  - Differential organization of the local immune response in patients with active
      cavitary tuberculosis or with nonprogressive tuberculoma.
AB  - BACKGROUND: In 90% of all cases, Mycobacterium tuberculosis infection results in
      latency rather than active disease, with the pathogen being contained within
      granulomatous lesions at the site of primary infection. Failure of this
      containment leads to reactivation of postprimary tuberculosis (TB). The regional
      immune processes that sustain the delicate balance with persistent M.
      tuberculosis, however, remain unclear. METHODS: We compared activation statuses,
      biological functions, and interactions of host immune cells in human
      nonprogressive tuberculoma and active cavitary tuberculous lung tissue. RESULTS:
      Dissection of early granuloma formations revealed differential cellular
      distribution and activation statuses of distinct cell types in different regions
      relative to the central caseotic caverna or the tuberculoma in tuberculous lung
      tissue. In patients with tuberculoma with latent infection, distant parts of lung
      tissue exhibited strong vascularization and profound proliferative activity,
      indicating that continuous immune defense is required for mycobacterial
      containment, which is absent in cavitary tuberculous lung lesions. CONCLUSIONS:
      We conclude that differential regulation of the local immune response is crucial
      for the containment of M. tuberculosis and that a continuous antigen-specific
      cross talk between the host immune system and M. tuberculosis is ensured during
      latency. This activation requires sufficient supply of nutrients and well
      coordinated structural organization, both of which are lost during reactivation
      of TB.

PMID- 15942899
TI  - Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit
      model of meningitis is dependent on phenolic glycolipid produced by the bacilli.
AB  - Infection with Mycobacterium tuberculosis in humans results in active disease in
      approximately 10% of immune-competent individuals, with the most-severe clinical
      manifestations observed when the bacilli infect the central nervous system (CNS).
      Here, we use a rabbit model of tuberculous meningitis to evaluate the severity of
      disease caused by the M. tuberculosis clinical isolates CDC1551, a highly
      immunogenic strain, and HN878 or W4, 2 members of the W/Beijing family of
      strains. Compared with infection with CDC1551, CNS infection with HN878 or W4
      resulted in higher bacillary loads in the cerebrospinal fluid and brain,
      increased dissemination of bacilli to other organs, persistent levels of tumor
      necrosis factor-alpha , higher leukocytosis, and more-severe clinical
      manifestations. This pathogenic process is associated with the production by
      HN878 of a polyketide synthase-derived phenolic glycolipid (PGL), as demonstrated
      by reduced virulence in rabbits infected with an HN878 mutant disrupted in the
      pks1-15 gene, which is required for PGL synthesis.

PMID- 15942900
TI  - Cytocidal effect of Streptococcus pyogenes on mouse neutrophils in vivo and the
      critical role of streptolysin S.
AB  - We analyzed the in vivo dynamics of peritoneal exudate cells (PECs) in mice
      injected with group A streptococcus (GAS). A live low-virulence strain, as well
      as heat-killed low- and high-virulence strains, significantly increased the
      number of PECs (primarily neutrophils), whereas a live high-virulence strain did
      not. When coinjected with thioglycollate, the live high-virulence strain, as well
      as most other GAS strains, suppressed the ability of thioglycollate to induce
      neutrophil exudation. This suppression was due to a cytocidal effect of GAS on
      exuded neutrophils rather than an inhibition of neutrophil migration. In
      addition, GAS enhanced the apoptosis of neutrophils. These cytocidal effects were
      significantly reduced by the deletion of functional streptolysin S from GAS. Our
      findings suggest that, in addition to the production of antiphagocytic factors
      and survival inside phagocytes, GAS uses a more aggressive method--the
      elimination of neutrophils--to evade the host's innate immune system.

PMID- 15942901
TI  - Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary
      pyogenic liver abscess and metastatic infection.
AB  - BACKGROUND: Primary pyogenic liver abscess (PLA) with septic complication by
      Klebsiella pneumoniae is an emerging infectious disease. METHODS AND RESULTS:
      Using DNA microarray hybridization, we identified a 20-kb chromosomal region that
      contained 15 open-reading frames (ORFs), including an iron-uptake system (kfu), a
      phosphoenolpyruvate sugar phosphotransferase system (PTS), and 6 unknown ORFs.
      The region was more prevalent among tissue-invasive strains (35/46) than among
      noninvasive strains (19/98) (P<.0001, chi2 test). To test the role played by this
      region in pathogenesis, 3 different deletion mutants (NTUH-K2044 [Delta kfu],
      K2044 [Delta ORF7-9], and K2044 [Delta PTS]) were constructed. Only the Delta
      kfuABC mutants showed decreased virulence in mice, compared with the wild-type
      strain. An in vitro assay confirmed the involvement of kfu in iron acquisition.
      There was a high correlation rate (85%) between the kfu/PTS region and 2 tissue
      invasion-associated chromosomal regions (allS and magA). Moreover, all 3 regions
      were present in strains that caused PLA plus endophthalmitis or meningitis.
      CONCLUSION: Our results suggest that chromosomal heterogeneity is present in
      tissue-invasive K. pneumoniae strains. A genotype containing all 3 regions is
      strongly associated with PLA and metastatic infection. These regions may serve as
      convenient markers for the rapid diagnosis of emergent tissue-invasive strains.

PMID- 15942902
TI  - Significant reduction in inflammatory response in the macaque model of chlamydial
      pelvic inflammatory disease with azithromycin treatment.
AB  - We inoculated 45 female macaques in the cervix with Chlamydia trachomatis once
      weekly for 5 weeks and randomly assigned them to treatment with doxycycline
      (n=12), azithromycin (n=12), or placebo (n=21). At hysterectomy, cervical
      cultures remained positive in 12 of 21 placebo-treated monkeys, versus 0 of 12
      doxycycline- or azithromycin-treated monkeys (P<.01); cervical ligase chain
      reaction remained positive in 15 placebo-, 1 doxycycline-, and 0 azithromycin
      treated monkeys. Tubal swabs remained positive in 3 placebo-, 1 doxycycline-, and
      0 azithromycin-treated monkeys. Immunopathologic damage was moderate to
      widespread in upper and lower reproductive-tract tissues from placebo- and
      doxycycline-treated monkeys but were significantly reduced in azithromycin
      treated monkeys. Transforming growth factor- beta was also significantly less
      prevalent in azithromycin-treated monkeys. Azithromycin treatment dramatically
      reduced the inflammatory response and was highly effective in eradicating C.
      trachomatis from the lower and upper reproductive tract (12/12), compared with
      doxycycline (7/12) and placebo (3/21).

PMID- 15942903
TI  - Mucosal lymphoid infiltrate dominates colonic pathological changes in murine
      experimental shigellosis.
AB  - BACKGROUND: Shigella species are invasive human pathogens that cause acute
      rectocolitis by triggering a dysregulated inflammatory reaction in the colonic
      and rectal mucosa. Because mice are naturally resistant to shigellosis, there is
      no mouse model that mimics human disease. We explore the susceptibility of
      intestinal flora-depleted mice to shigellosis after intragastric infection with
      Shigella strains. METHODS: Mice given 5 g/L streptomycin as a beverage were
      infected intragastrically with 1 x 108 cfu of either invasive or noninvasive
      Shigella strains. RESULTS: We found that invasive Shigella strains persist up to
      30 days in feces, whereas the persistence of noninvasive Shigella strains was
      reduced. Colonization primarily involves the colon and the cecum and, to a lesser
      extent, the ileum. The hallmark of inflammation in the intestinal tissue is a
      dramatic expansion of the lymphoid follicles, in which a high apoptotic index is
      recorded. CONCLUSIONS: We provide a murine model in which shigellae are able to
      reach their natural tissue target: the colon. Moreover, the absence of
      polymorphonuclear leukocyte recruitment and of epithelial cell lesions reveal
      some aspects of shigellosis that are usually hidden by the prevalence of this
      cell population. This novel model may contribute to the identification of new
      targets for vaccines and therapies.

PMID- 15942904
TI  - Gene dosage determines the negative effects of polymorphic alleles of the P2X7
      receptor on adenosine triphosphate-mediated killing of mycobacteria by human
      macrophages.
AB  - BACKGROUND: Stimulation of the P2X7 purinergic receptor (P2X7) in bacille
      Calmette-Guerin (BCG)-infected human macrophages with extracellular adenosine
      triphosphate (ATP) leads to pore formation and killing of mycobacteria. We
      examined the effect of polymorphisms in the P2X7 gene (P2X7) on the capacity of
      macrophages to kill mycobacteria. METHODS: Polymorphisms and mutations in P2X7
      were identified by both DNA sequence analysis and determination of uptake of
      ethidium by time-resolved flow cytometry. Macrophages from affected subjects were
      infected with Mycobacterium bovis BCG. Apoptosis was determined by use of Annexin
      V staining, and BCG growth was determined by use of quantitative mycobacterial
      cultures. RESULTS: Three new mutations were identified. Macrophages from subjects
      heterozygous for a polymorphism in P2X7 had a 50% reduction in uptake of ethidium
      and a 75% reduction in the number of apoptotic cells, compared with macrophages
      from wild-type (wt) subjects, after stimulation with interferon (IFN)- gamma and
      ATP. Furthermore, after stimulation with IFN- gamma and ATP, there was a
      reduction in BCG growth of up to approximately 0.5 log10 in macrophages from
      single-heterozygous subjects, compared with a reduction of 1.0 log10 in
      macrophages from wt subjects. Interestingly, BCG-infected macrophages from
      compound-heterozygous subjects, for different combinations of polymorphisms in
      P2X7, had no uptake of ethidium, failed to undergo apoptosis, and were unable to
      kill mycobacteria after stimulation with IFN- gamma and ATP. CONCLUSIONS: Various
      polymorphisms in P2X7 abrogate IFN- gamma /ATP-induced killing of mycobacteria by
      human macrophages and, thus, may contribute to variability in susceptibility to
      mycobacterial infections.

PMID- 15942905
TI  - Recurrent antiviral-resistant genital herpes in an immunocompetent patient.
AB  - Herpes simplex virus type 2 (HSV-2) resistance to antiviral drugs has been
      described primarily in immunocompromised patients. We report an apparently
      immunocompetent, human immunodeficiency virus-negative male patient who has
      experienced repeated HSV-2 genital outbreaks despite receiving antiviral
      prophylaxis with several different drugs. Several of the HSV-2 genital isolates
      from this patient have been confirmed as resistant to acyclovir and penciclovir.
      Antiviral resistance occurred in the setting of long-term prednisone treatment
      and intermittent acyclovir prophylaxis at suboptimal doses and persisted despite
      the cessation of oral steroid treatment. The patient's genital herpes outbreaks
      were not controlled by high-dose prophylaxis with acyclovir, valacyclovir, and
      famciclovir. Cessation of antiviral prophylaxis resulted in reversion of this
      patient's HSV-2 isolates to acyclovir and penciclovir sensitivity, although
      resistant virus reappeared when antiviral prophylaxis was resumed. Transmission
      of a sensitive HSV-2 strain from this patient to a female sex partner was
      observed. These observations confirm previous reports that resistance to
      acyclovir may develop during prophylactic therapy in an otherwise well,
      immunocompetent patient. These findings support the conclusion that both drug
      sensitive and drug-resistant HSV-2 strains established latency in this patient
      and that both strains are capable of frequent reactivation.

PMID- 15942906
TI  - Protective effect of the HLA-Bw4I80 epitope and the killer cell immunoglobulin
      like receptor 3DS1 gene against the development of hepatocellular carcinoma in
      patients with hepatitis C virus infection.
AB  - The aim of the present study was to investigate, in 152 Spanish patients infected
      with hepatitis C virus (HCV), the possibility that killer cell immunoglobulin
      like receptors (KIRs) influence progression to hepatocellular carcinoma. KIRs are
      related to the activation and inhibition of natural killer cells and may play an
      important role in the innate response against infection with such viruses as HCV.
      We found that the human leukocyte antigen-Bw4I80 epitope and the KIR3DS1 gene
      were more frequent in HCV carriers than in patients with hepatocellular
      carcinoma. Moreover, these associations were not independent of each other--the
      KIR3DS1/Bw4I80 genotype clearly was also more frequent in HCV carriers (odds
      ratio, 24.22).

PMID- 15942907
TI  - Antibody avidity maturation during severe acute respiratory syndrome-associated
      coronavirus infection.
AB  - The maturation of virus-specific immunoglobulin G avidity during severe acute
      respiratory syndrome-associated coronavirus infection was examined. The avidity
      indices were low (mean +/- SD, 30.8% +/- 11.6%) among serum samples collected <
      or =50 days after fever onset, intermediate (mean +/- SD, 52.1% +/- 14.1%) among
      samples collected between days 51 and 90, and high (mean +/- SD, 78.1% +/- 8.0%)
      among samples collected after day 90. Avidity indices of 40% and 55% could be
      considered as cutoff values for determination of recent (< or =50 days) and past
      (>65 days) infection, respectively. Measurement of antibody avidity can be used
      to differentiate primary infection from reexposure and to assess humoral
      responses to candidate vaccines.

PMID- 15942908
TI  - Saline-filled breast implant contamination with Curvularia species among women
      who underwent cosmetic breast augmentation.
AB  - BACKGROUND: During December 2000-July 2001, black sediment was noted in saline
      filled silicone breast implants of women who had undergone revision surgery at
      facility A. Curvularia fungus was isolated from implant saline. METHODS: To
      identify risk factors for contamination with Curvularia species, we performed
      case-control, retrospective cohort, and laboratory studies and conducted
      procedural reviews. A case patient was defined as any woman who underwent
      revision surgery at facility A between January 2000 and June 2001 and had black
      sediment in her implants. RESULTS: Five patients met the case definition.
      Contamination was associated with having had surgery performed in operating room
      (OR) 2 (4/88 vs. 1/140; P=.07) and a longer duration of surgery (P<.001). A
      longer duration spent in the OR was an additional risk factor (P=.005).
      Curvularia fungus was isolated from the sterile supply room, where saline bottles
      had been stored under a water-damaged ceiling, and from the corridor outside OR
      2; it was also found more commonly from facility A personnel than from non
      facility A personnel (12/34 vs. 4/60; P<.001). Saline was warmed in a cabinet
      opposite OR 2, which was maintained at negative pressure differentials, then was
      poured into bowls open to the OR 2 environment before injection into implants.
      CONCLUSION: Surgeons should always use closed systems to inflate breast implants.
      Surgery center infection control measures must include moisture control and
      balanced ventilation systems.

PMID- 15942909
TI  - Sickle cell trait and the risk of Plasmodium falciparum malaria and other
      childhood diseases.
AB  - BACKGROUND: The gene for sickle hemoglobin (HbS) is a prime example of natural
      selection. It is generally believed that its current prevalence in many tropical
      populations reflects selection for the carrier form (sickle cell trait [HbAS])
      through a survival advantage against death from malaria. Nevertheless, >50 years
      after this hypothesis was first proposed, the epidemiological description of the
      relationships between HbAS, malaria, and other common causes of child mortality
      remains incomplete. METHODS: We studied the incidence of falciparum malaria and
      other childhood diseases in 2 cohorts of children living on the coast of Kenya.
      RESULTS: The protective effect of HbAS was remarkably specific for falciparum
      malaria, having no significant impact on any other disease. HbAS had no effect on
      the prevalence of symptomless parasitemia but was 50% protective against mild
      clinical malaria, 75% protective against admission to the hospital for malaria,
      and almost 90% protective against severe or complicated malaria. The effect of
      HbAS on episodes of clinical malaria was mirrored in its effect on parasite
      densities during such episodes. CONCLUSIONS: The present data are useful in that
      they confirm the mechanisms by which HbAS confers protection against malaria and
      shed light on the relationships between HbAS, malaria, and other childhood
      diseases.

PMID- 15942911
TI  - Therapeutic response of HIV-1 subtype C in African patients.

PMID- 15942912
TI  - Herbal medications commonly used in the practice of rheumatology: mechanisms of
      action, efficacy, and side effects.
AB  - OBJECTIVE: To review the literature on herbal preparations commonly utilized in
      the treatment of rheumatic indications. METHODS: Search of MEDLINE (PubMed) was
      performed using both the scientific and the common names of herbs. Relevant
      articles in English were collected from PubMed and reviewed. RESULTS: This review
      summarizes the efficacy and toxicities of herbal remedies used in complementary
      and alternative medical (CAM) therapies for rheumatologic conditions, by
      elucidating the immune pathways through which these preparations have
      antiinflammatory and/or immunomodulatory activity and providing a scientific
      basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting
      as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by
      reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta
      gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but
      not for Sjogrens disease. The antiinflammatory actions of Harpagophytum
      procumbens is due to its action on eicosanoid biosynthesis and it may have a role
      in treating low back pain. While in vitro experiments with Tanacetum parthenium
      found inhibition of the expression of intercellular adhesion molecule-1, tumor
      necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a
      decrease in T-cell adhesion, to date human studies have not proven it useful in
      the treatment of RA. Current experience with Tripterygium wilfordii Hook F,
      Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while
      Urtica diocia and willow bark extract are effective for osteoarthritis. T.
      wilfordii Hook F extract inhibits the production of cytokines and other mediators
      from mononuclear phagocytes by blocking the up-regulation of a number of
      proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon
      gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both
      decrease the production of TNF-alpha. At present there are no human studies on
      Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic,
      antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF
      alpha, prostaglandin, and leukotriene synthesis and at present has limited
      efficacy in the treatment of osteoarthritis. CONCLUSIONS: Investigation of the
      mechanism and potential uses of CAM therapies is still in its infancy and many
      studies done to date are scientifically flawed. Further systematic and scientific
      inquiry into this topic is necessary to validate or refute the clinical claims
      made for CAM therapies. An understanding of the mechanism of action of CAM
      therapies allows physicians to counsel effectively on their proper and improper
      use, prevent adverse drug-drug interactions, and anticipate or appreciate
      toxicities. RELEVANCE: The use of CAM therapies is widespread among patients,
      including those with rheumatic diseases. Herbal medications are often utilized
      with little to no physician guidance or knowledge. An appreciation of this
      information will help physicians to counsel patients concerning the utility and
      toxicities of CAM therapies. An understanding and elucidation of the mechanisms
      by which CAM therapies may be efficacious can be instrumental in discovering new
      molecular targets in the treatment of diseases.

PMID- 15942913
TI  - Adult Kawasaki disease: report of two cases and literature review.
AB  - OBJECTIVES: To describe 2 cases of adult Kawasaki Disease (KD) and to review the
      medical literature to better define the epidemiological, clinical, laboratory,
      histopathological, cardiovascular, and therapeutic aspects of adult KD compared
      with pediatric KD. METHODS: Report of 2 cases, and review of the literature using
      a Medline search from 1967 to June 2003. RESULTS: Including our 2 cases, there
      are 57 reports of adult KD, 74% among patients aged 18 to 30 years. Nine cases of
      KD associated with human immunodeficiency virus (HIV) infection were described,
      suggesting that an immunocompromised state may predispose to this syndrome. The
      incidence of specific diagnostic criteria was roughly similar in adults and in
      children. However, cheilitis, meningitis, and thrombocytosis were observed in a
      larger percentage of children, while arthralgia, adenopathy, and liver function
      abnormality were more common in adults. Although adult KD often was diagnosed
      after the acute phase, when a significant beneficial effect from gammaglobulin
      infusion could not be expected, this treatment did appear to shorten the course
      of the disease. Coronary aneurysms were less frequent in adults than in children.
      Prognosis was more favorable in adults, with less cardiovascular complications
      and no deaths. CONCLUSIONS: Adult KD is a rare condition, which may go
      unrecognized. Other known disease processes with similar clinical presentations
      such as hypersensitivity drug reaction and toxic shock syndrome must be ruled
      out. For adult KD, exclusion criteria such as absence of hypotension, visceral
      impairment, staphylococcal infection, and any drug able to induce a drug
      hypersensitivity reaction are suggestive of the diagnosis, in the presence of the
      inclusion criteria, rash, conjunctival effusion, oropharynx changes, extremity
      changes, or adenopathy.

PMID- 15942914
TI  - Do health-related quality-of-life domains and items in knee and hip
      osteoarthritis vary in importance across social-cultural contexts? A qualitative
      systematic literature review.
AB  - OBJECTIVES: To identify and summarize the existing literature on domains/items of
      health-related quality of life (HRQoL) that are important for patients with knee
      or hip osteoarthritis (OA) in various sociocultural contexts and critically
      evaluate existing OA-specific HRQoL instruments based on the important
      domains/items identified. METHODS: A qualitative systematic literature review was
      performed using (1) an electronic search of Medline, PsycINFO, ISI Web of
      Knowledge, and the Cochrane Library (using 29 relevant keywords), and (2) a
      manual search of relevant journals, textbooks, and bibliographies. Titles and
      abstracts were reviewed using predefined criteria to select potential articles
      for full text review. RESULTS: From 20,768 reviewed references, 77 articles were
      selected for full text review, of which 15 articles fulfilled inclusion criteria.
      Studies were conducted in English (4 each in the United States and Canada, 2 in
      the United Kingdom, and 1 in Ireland), French (n = 2), and Swedish (n = 2).
      Important HRQoL domains in 1 or more countries included pain, physical
      disability, sports/recreational activities, other symptoms of OA, mental health,
      social health, and knee/hip-related quality of life. Items within each domain
      varied from country to country except some physical disability items. The paucity
      of available information did not allow adequate assessment of OA-specific
      instruments coverage of important domains/items in various sociocultural
      contexts. CONCLUSIONS: A surprisingly sparse literature reports the important
      HRQoL domains/items from the perspective of patients with knee or hip OA.
      Additional studies are needed to determine the important domains/items for these
      patients and to confirm that OA-specific measures are truly accurate and
      comprehensive when applied in various sociocultural contexts.

PMID- 15942915
TI  - Calcinosis in rheumatic diseases.
AB  - BACKGROUND: Calcinosis, or dystrophic soft-tissue calcification, occurs in
      damaged or devitalized tissues in the presence of normal calcium/phosphorus
      metabolism. It is often noted in the subcutaneous tissues of connective tissues
      diseases--primarily systemic lupus erythematosus, scleroderma, or dermatomyositis
      -and may involve a relatively localized area or be widespread. The calcinotic
      accumulations may lead secondarily to muscle atrophy, joint contractures, and
      skin ulceration complicated by recurrent episodes of local inflammation and
      infection. OBJECTIVES: To review the classification, pathogenesis, clinical
      features, and treatment of calcinosis in rheumatic diseases. METHOD: A MEDLINE
      search of articles from 1972 to 2004 was conducted utilizing the index word
      "calcinosis" with the coindexing terms "scleroderma," "lupus," "dermatomyositis,"
      and "dystrophic calcification." RESULTS: Calcinosis may be the source of both
      pain and disability in connective tissue disease patients. Illustrative cases of
      patients with severe calcinosis are described. The literature available was
      critically reviewed. While warfarin, colchicine, probenecid, bisphosphonates,
      diltiazem, minocycline, aluminum hydroxide, salicylate, surgical extirpation, and
      carbon dioxide laser therapies have been used, no treatment has convincingly
      prevented or reduced calcinosis. CONCLUSIONS: Calcinosis is common in the
      conditions reviewed and a number of agents have been used for treatment. However,
      the approach to calcinosis management is disorganized, beginning with the lack of
      a generally accepted classification and continuing with a lack of systematic
      study and clinical therapeutic trials.

PMID- 15942916
TI  - The spectrum of familial Mediterranean fever gene mutations in Arabs: report of a
      large series.
AB  - OBJECTIVES: To identify the frequency and distribution of familial Mediterranean
      fever (FMF) gene (MEFV) mutations in Arab patients. PATIENTS AND METHODS: The
      study was performed in the pediatric FMF clinic of Jordan University Hospital
      over a period of 4 years. Patients were referred by their physicians for
      diagnosis, management, genetic study, and counseling. A diagnosis of FMF was made
      according to published criteria. Screening for 5 mutations, namely M694V, V726A,
      M694I, M680I, and E148Q, was performed by amplification refractory mutation
      system (ARMS) for the first 4 and by restriction endonuclease testing for E148Q.
      RESULTS: Of the 407 unrelated patients investigated, 239 (59%) had 1 or 2
      mutations and 168 (41%) had none of the studied mutations detected. Of those with
      mutations, 92 were homozygous, 53 were compound heterozygotes, 3 had complex
      alleles, and 91 patients had only 1 identifiable mutation. Of the mutations,
      M694V, V726A, M694I, M680I, and E148Q accounted for 38, 26, 14, 10 and 13%,
      respectively. Twelve of our patients developed the protracted febrile myalgia
      syndrome (PFMS) of whom 5 (42%) were homozygous for M694V. Only 2 developed
      chronic renal failure, both of whom were homozygous for M694V and were not on
      colchicine prophylaxis. However, 43 patients had a family history of chronic
      renal failure, and 15 (35%) were homozygous for M694V. CONCLUSIONS: Our data
      indicate that the 5 MEFV mutations are well distributed in Arabs. They also show
      that M694V is the most common mutation in Arab patients with FMF and seems to
      have an association with the development of amyloidosis and the PFMS. The high
      frequency of V726A, and the unique high frequency of M694I in Arabs compared with
      3 other ethnic groups, are confirmed.

PMID- 15942917
TI  - The benefit/risk profile of TNF-blocking agents: findings of a consensus panel.
AB  - OBJECTIVE: To review the benefits and risks associated with the use of the tumor
      necrosis factor (TNF)-blockers in various indications (eg, rheumatoid arthritis
      [RA], Crohn's disease [CD], psoriasis). METHODS: The members of the consensus
      panel were selected based on their expertise. Centocor, Inc provided an
      educational grant to the Center for Health Care Education to facilitate the
      consensus panel. Peer-reviewed articles discussing clinical studies and clinical
      experiences with TNF-blockers form the basis of this review. Emerging data that
      have not been peer-reviewed are also included. RESULTS: The TNF-blockers
      infliximab, etanercept, and adalimumab are all approved for treatment of RA. All
      3 are effective, and there are currently no published data from head-to-head
      clinical trials to support using 1 agent over another. Preliminary data from
      small, retrospective studies indicate that switching among agents to overcome
      inadequate efficacy or poor tolerability is beneficial in some patients. The only
      TNF-blocker currently approved for the induction and maintenance of remission in
      CD is infliximab. Preliminary data indicate that etanercept and infliximab are
      effective in treating psoriasis. Some risks associated with TNF-blockers have
      become apparent, including congestive heart failure, demyelinating diseases, and
      systemic lupus erythematosus, but in most cases can be identified and managed.
      Several of these risks (eg, lymphoma and serious infections) are associated with
      either the condition per se or the concomitant medication use. Simple screening
      procedures help manage the risk of tuberculosis infection; however, it is
      recommended that physicians and patients be alert to the development of any new
      infection so that appropriate treatment may be initiated promptly. Rare infusion
      reactions, particularly with infliximab, may also be effectively managed.
      CONCLUSION: TNF-blockers are effective and may be safely used for short- and long
      term management of RA or CD. TNF-blockers also show efficacy in other emerging
      indications.

PMID- 15942918
TI  - Solving the Poisson-Boltzmann equation with the specialized computer chip MD
      GRAPE-2.
AB  - The accurate description of solvation effects is highly desirable in numerous
      computational chemistry applications. One widely used methodology treats the
      solvent as a uniform continuum ("implicit solvation"), and describes its net
      interaction with the solute by solving the Poisson-Boltzmann (PB) equation using
      the Boundary Element Method (BEM). These calculations are very time consuming
      using conventional computers. A new, efficient way of solving the PB equation on
      the special-purpose hardware chip MDGRAPE-2 is presented. The MDGRAPE-2 chip was
      originally developed to speed up the calculation of pairwise van der Waals and
      electrostatic interactions. By recasting the BEM equations and applying an
      iterative solution procedure, a hardware-accelerated PB solver on MDGRAPE-2 could
      be implemented. The performance and reliability of the method is demonstrated on
      three examples ranging from small peptides to large proteins, whereby the
      obtained acceleration factors range from 15-fold to up to 40-fold with no loss of
      accuracy compared to the conventional approach.

PMID- 15942921
TI  - Increased pressure at the electrospray interface dramatically raises sensitivity
      in analysis of denaturated proteins.

PMID- 15942922
TI  - Uterine fibroid embolization: where are we and where should we go?

PMID- 15942923
TI  - A new three-dimensional automatic bodymarker system for transvaginal
      ultrasonography.
AB  - OBJECTIVE: To evaluate the accuracy and usefulness of a newly developed three
      dimensional automatic bodymarker system for transvaginal ultrasonography.
      METHODS: A bodymarker system which utilizes an electromagnetic field to specify
      the probe position was developed. Software was written which enabled the
      positional information of the probe and the ultrasound image to be simultaneously
      displayed on a personal computer. The bodymarker was displayed as a three
      dimensional graphic model. The differences between the estimated and the actual
      position--i.e. the error--for both position (x, y and z) and angles (azimuth,
      elevation and roll) of the probe were measured. The movement of the probe was
      then evaluated in healthy female volunteers and the comparative time required for
      ultrasound examination was determined. RESULTS: Both the position and the angles
      of the probe were accurately shown in the computer display. The errors were 1.0
      mm and 0.7 degrees (median) for position and angle, respectively. The system was
      also shown to work well in healthy female volunteers. Calibration of the new
      system required only 5.0 seconds, compared with an average of 7.6 seconds for the
      conventional bodymarker. CONCLUSION: The newly developed three-dimensional
      automatic transvaginal bodymarker system provides an accurate indication of probe
      position and its tilting angle. It works well in healthy female volunteers and
      speeds up the examination time. It may be clinically useful for transvaginal
      ultrasound examination.

PMID- 15942924
TI  - Carbohydrate-encapsulated gold nanoparticles for rapid target-protein
      identification and binding-epitope mapping.

PMID- 15942925
TI  - Mammalian transcription activation domains of VP16, AP2 and CTF activate
      transcription in a whole cell extract from Schizosaccharomyces pombe through the
      SRB/mediator.
AB  - The acidic-rich activation domain of VP16 and the proline-rich activation domains
      of human AP2 and human CTF are able to activate transcription in a whole cell
      extract from Schizosaccharomyces pombe, whereas the glutamine-rich domains of Sp1
      and Oct2 are unable to activate transcription in this system. Immunodepletion
      experiments of the whole cell extracts using specific antibodies against pombe
      TAF110, pombe TAF 72, pombe TBP and Srb4 shows that the activation of
      transcription by VP16, AP2 and CTF is through the mediator, since depletion of
      Srb4 inhibits activated transcription but does not inhibit basal transcription.
      Immunodepletion of TBP causes inhibition of both activated and basal
      transcription. On the other hand, immunodepletion of TAFs does not have an effect
      on either activated or basal transcription. Purified RNA polymerase holoenzyme is
      able to rescue the transcriptional activation activity of the anti-Srb4
      immunodepleted extract. Moreover, we demonstrate that the mediator is needed for
      basal transcription of a TATA-less promoter.

PMID- 15942926
TI  - An extracellular lipase from the dimorphic yeast Arxula adeninivorans: molecular
      cloning of the ALIP1 gene and characterization of the purified recombinant
      enzyme.
AB  - The lipase-encoding Arxula adeninivorans ALIP1 gene was isolated using fragments
      of lipase isolates obtained by trypsin digestion for the definition of
      oligonucleotide primers in a PCR screening approach. The gene harbours an ORF of
      1347 bp encoding a 420 amino acid protein of some 50 kDa preceded by an N
      terminal 28 prepro-secretion sequence. The deduced amino acid sequence was found
      to be similar to the lipases from Candida albicans and C. parapsilosis (34-38%
      identity) and more distantly related to other lipases. The sequence contains the
      consensus pentapeptide motif (-Gly-X-Ser-X-Gly-) that forms a part of the
      interfacial lipid recognition site in lipases. The expression of the gene is
      regulated by carbon source. In media supplemented with Tween 20, induction of the
      ALIP1 gene and accumulation of the encoded lipase in the medium is observed, thus
      demonstrating gene regulation by lipophilic compounds. The enzyme characteristics
      are analysed from isolates of native strains as well as from those of recombinant
      strains expressing the ALIP1 gene under control of the strong A. adeninivorans
      derived TEF1 promoter. For both proteins a molecular mass of 100 kDa was
      determined, indicating a dimeric structure, a pH optimum at pH 7.5 and a
      temperature optimum at 30 degrees C. The enzyme hydrolyses all ester bonds in all
      triglyceride substrates tested. Middle-sized chain fatty acids are more
      efficiently hydrolysed than short- and long-chain fatty acids, with the highest
      activity on C8/C10 fatty acid esters pNP-caprylate, pNP-caprate and tricaprylin.

PMID- 15942927
TI  - Investigation of penetratin peptides. Part 2. In vitro uptake of penetratin and
      two of its derivatives.
AB  - As endocytic uptake of the Antennapedia homeodomain-derived penetratin peptide
      (RQIKIWFQNRRMKWKK) is finally being revealed, some of the early views about
      penetratin need to be reconsidered. Endocytic uptake seems to contradict the
      indispensability of tryptophans and also the minimum length of 16 amino acid
      residues for efficient internalization. To revise the membrane translocation of
      penetratin, two penetratin analogs were designed and synthesized: a peptide in
      which tryptophans were replaced by phenylalanines (Phe(6,14)-penetratin,
      RQIKIFFQNRRMKFKK) and a shortened analog (dodeca-penetratin, RQIKIWF-R-KWKK) made
      up of only 12 residues. The peptides were fluorescently labeled and applied to
      live, unfixed cells from various lines. Cellular uptake was analysed by confocal
      microscopy and flow cytometry. Low temperature or ATP-depletion blocked the
      intracellular entry of all three penetratin peptides. A decrease in membrane
      fluidity or cholesterol depletion with methyl-beta-cyclodextrin greatly inhibited
      peptide uptake, showing the involvement of cholesterol-rich lipid rafts in
      internalization. Exogenous heparan sulfate also diminished the internalization of
      penetratin and its derivatives, reflecting the paramount importance of
      electrostatic interactions with polyanionic cell-surface proteoglycans. The
      beneficial presence of tryptophans is supported by observations on the decreased
      cellular uptake of Phe(6, 14)-penetratin. The maintained translocational
      efficiency of dodeca-penetratin demonstrates that a thorough understanding of
      penetratin internalization can yield new penetratin analogs with unaltered
      translocational abilities. This study provides evidence on the energy-dependent
      and lipid raft-mediated endocytic uptake of penetratin and highlights the
      necessity of revealing those pathways that cationic cell-penetrating peptides
      employ to enter live cells.

PMID- 15942928
TI  - Characterization of a sialidase (neuraminidase) isolated from Clostridium
      chauvoei (Jakari strain).
AB  - A sialidase from Clostridium chauvoei (Jakari strain), an indigenous bacterial
      strain that causes blackleg in Nigerian cattle and other ruminants was isolated
      and partially purified by chromatography on DEAE cellulose, hydroxyapatite and
      phenyl agarose columns. The enzyme migrated as a 65-kDa protein after
      electrophoresis on sodium dodecyl sulphate polyacrylamide gels. It was optimally
      active at pH 4.5 and 40 degrees C with an activation energy (Ea) of 13.40 kJ mol(
      1). It had Km and Vmax values of 170 microM and 200 micromole h(-1) mg(-1)
      respectively with fetuin as substrate. When sialyllactose (Neu5Ac2,3 lactose) was
      used as substrate the Km and Vmax values were 8 microM and 5 micromoles min(-1)
      mg(-1) respectively. The Clostridium chauvoei sialidase cleaved sialic acids from
      RBC ghosts of sheep, horse, goat, cattle, pig and mice as well as mouse brain
      cells, albeit at different rates. The enzyme was activated by Ca2+ and Mg2+ and
      inhibited by the group-specific reagents diethylpyrocarbonate (DEP) and N
      ethylmalemide (NEM). The sialidase inhibitors, 2,3 didehydroneuraminic acid
      (Neu5Ac2,3en) and paranitrophenyl oxamic acid (pNPO) inhibited the enzyme
      competitively with Ki values of 40 and 30 microM respectively.

PMID- 15942929
TI  - The Saccharomyces cerevisiae Sub2 protein suppresses heterochromatic silencing at
      telomeres and subtelomeric genes.
AB  - We show that overexpression of Sub2p, a multifunctional Saccharomyces cerevisiae
      helicase family member that is involved in mRNA elongation and transport, also
      suppresses heterochromatic silencing at telomeres. Genetic assays show cells that
      overexpress SUB2 from a high copy plasmid exhibit increased survival rates when
      selecting for a telomere-silenced URA3 reporter. Two temperature-sensitive sub2
      mutations that affect different helicase domains were also examined at the
      permissive temperature; these mutants also overcome silencing of the URA3
      reporter. The degree to which silencing is suppressed correlates with SUB2 RNA
      and protein levels. Additionally, we find that Sub2p localizes to the telomeres,
      as determined by chromatin immunoprecipitation assays, suggesting that Sub2p has
      a direct effect at telomeres. Genome-wide analysis of transcripts was used to
      assess whether Sub2p overproduction affects only the silenced URA3 reporter gene,
      or whether other subtelomeric genes are also affected. Of the 70 RNA transcripts
      elevated in the Sub2p overexpressing cells, 28% are encoded by subtelomeric genes
      that are located within 5 Kbp of a core X or Y' repeat. The remainder of the
      transcripts clustered into several functional groups, including the iron
      homeostasis pathway, purine nucleotide metabolism, and miscellaneous transport
      genes, among others. These results suggest a targeted effect of Sub2p on
      transcription. Our results also confirm that Sub2p affects heterochromatic gene
      expression, similar to that observed with the Drosophila Hel25E homologue. The
      above observations imply that Sub2p affects chromatin structure in addition to,
      or in parallel with, its functions in transcription elongation, splicing and mRNA
      transport.

PMID- 15942930
TI  - Evolutionary combinatorial chemistry, a novel tool for SAR studies on peptide
      transport across the blood-brain barrier. Part 2. Design, synthesis and
      evaluation of a first generation of peptides.
AB  - The use of high-throughput methods in drug discovery allows the generation and
      testing of a large number of compounds, but at the price of providing redundant
      information. Evolutionary combinatorial chemistry combines the selection and
      synthesis of biologically active compounds with artificial intelligence
      optimization methods, such as genetic algorithms (GA). Drug candidates for the
      treatment of central nervous system (CNS) disorders must overcome the blood-brain
      barrier (BBB). This paper reports a new genetic algorithm that searches for the
      optimal physicochemical properties for peptide transport across the blood-brain
      barrier. A first generation of peptides has been generated and synthesized. Due
      to the high content of N-methyl amino acids present in most of these peptides,
      their syntheses were especially challenging due to over-incorporations, deletions
      and DKP formations. Distinct fragmentation patterns during peptide cleavage have
      been identified. The first generation of peptides has been studied by evaluation
      techniques such as immobilized artificial membrane chromatography (IAMC), a cell
      based assay, log Poctanol/water calculations, etc. Finally, a second generation
      has been proposed.

PMID- 15942931
TI  - Synthesis and biological characterization of human monocyte chemoattractant
      protein 1 (MCP-1) and its analogs.
AB  - Novel analogs of human monocyte chemoattractant protein 1 (MCP-1) were designed,
      synthesized and characterized to be used as tools to generate monoclonal
      antibodies as potential human therapeutics. MCP-1 and three analogs were
      synthesized by step-wise Fmoc solid phase synthesis. After oxidation to form the
      two-disulfide bonds, affinity chromatography using an immobilized mouse anti
      human MCP-1 monoclonal antibody (mAb) was utilized for a simple and highly
      effective purification procedure for the proteins. The final products were
      extensively characterized and compared with recombinant human MCP-1 (rhMCP-1).
      All proteins showed identical binding with mouse anti-human MCP-1 mAbs as
      measured by surface plasmon resonance. Synthetic MCP-1 and the analogs were
      comparable to recombinant MCP-1 in competition radio-ligand binding to CCR2
      receptors on THP-1 cells, and MCP-1-induced, calcium mobilization and chemotaxis
      assays.

PMID- 15942932
TI  - The ubiquitin ligase SCFGrr1 is necessary for pheromone sensitivity in
      Saccharomyces cerevisiae.
AB  - The presence of the appropriate pheromone induces alpha and a cells of the yeast
      Saccharomyces cerevisiae to activate both changes in transcriptional expression
      and cell polarity that eventually lead to the mating of alpha and a cells to form
      a/alpha diploid cells. A third response after exposure to mating pheromone is a
      transient cell cycle arrest, allowing synchronization of the two cell types in G1
      prior to cell fusion. At least in part, this cell cycle arrest requires the
      inactivation of Cln-kinase activity through transcriptional inactivation of the
      CLN1 and CLN2 genes, degradation of the Cln proteins and direct inhibition of Cln
      kinase complexes. Here we report that GRR1, which encodes a substrate recognition
      subunit of SCF complexes, is critical for pheromone sensitivity and likely for
      this arrest. Loss of SCF(Grr1) function by deletion of the GRR1 gene causes
      pheromone resistance. However, deletion of CLN1 and CLN2 restores pheromone
      sensitivity to grr1Delta cells. Thus, rapid loss of Cln-kinase activity during
      mating may require coordinated inactivation of the Cln-kinase complexes,
      inactivation of CLN transcription and SCF(Grr1)-dependent Cln degradation.

PMID- 15942933
TI  - Doxycycline, the drug used to control the tet-regulatable promoter system, has no
      effect on global gene expression in Saccharomyces cerevisiae.
AB  - The tet-regulatable promoter system is commonly used for genetic studies in many
      eukaryotic organisms. The promoter is regulated using doxycycline. There are no
      obvious phenotypic effects observed when doxycycline is added to the growth
      medium of yeast to control expression from the promoter. It is widely accepted
      that doxycycline is innocuous to yeast. Global genetic studies are now
      commonplace and the tetO-system is being used in transcriptome studies. Hence, we
      wanted to ensure that the absence of phenotypic effects, on addition of
      doxycycline to the growth medium, is mirrored in transcriptome data. We have
      demonstrated that doxycycline has no significant effect on global transcription
      levels and will continue to use the tetO-regulatable promoter system for genetic
      studies.

PMID- 15942934
TI  - Functional analysis of the Zygosaccharomyces rouxii Fps1p homologue.
AB  - The osmotolerant yeast Zygosaccharomyces rouxii accumulates the polyols glycerol
      and D-arabitol intracellularly in response to hyperosmotic stress, but the
      membrane transport proteins regulating polyol accumulation have not been studied.
      We have cloned and characterized a FPS1 homologue in Z. rouxii NRRL Y2547, and
      its sequence revealed a 2709 bp open reading frame encoding a peptide of 692
      deduced amino acids with 56.9% identity to the Saccharomyces cerevisiae Fps1p.
      The role of this putative membrane channel protein in polyol accumulation and
      release during osmoregulation was investigated. The Z. rouxii FPS1 (ZrFPS1)
      complemented the S. cerevisiae fps1Delta growth defect and glycerol release upon
      hypo-osmotic shock. Deletion of ZrFPS1 did not affect growth on glycerol as sole
      carbon source, suggesting that other transport proteins are involved in the
      uptake of glycerol. However, mutants lacking ZrFPS1 exhibited a significant
      decrease in glycerol and D-arabitol efflux and poor growth during hypo-osmotic
      conditions, suggesting that ZrFPS1 might be involved in D-arabitol transport in
      addition to glycerol. This is the first demonstration of a yeast gene that
      affects D-arabitol transport. The full-length ZrFPS1 gene sequence including
      upstream promoter has been deposited in the public database under Accession No.
      AY488133.

PMID- 15942935
TI  - Synthesis, liposomal formulation and thermal effects on phospholipid bilayers of
      leuprolide.
AB  - A novel liposomal formulation was developed for the encapsulation of the
      oligopeptide leuprolide (GlpHisTrpSerTyr-D-LeuLeuArgProNHEt), a potent analogue
      of gonadotropin releasing hormone used in the treatment of advanced prostate
      cancer, endometriosis and precocious puberty. Leuprolide was synthesized using
      solid phase methodology on a {3-[(ethyl-Fmoc-amino)-methyl]-1-indol-1-yl}-acetyl
      AM resin and Fmoc/tBu chemistry. The new liposomal formulation, called 'liposomes
      in liposomes' is composed of egg
      phosphatidylcholine:dipalmitoylphosphatidylglycerol in a molar ratio of
      98.91:1.09 (internal liposomes) and egg
      phosphatidylcholine:dipalmitoylphosphatidylglycerol:cholesterol in a molar ratio
      of 68.71:0.76:30.53 (external liposomes). It offers high encapsulation efficiency
      (73.8% for leuprolide); it can provide new delivery characteristics and it may
      have possible advantages in future applications regarding the encapsulation and
      delivery of bioactive peptides to target tissues. Furthermore, the
      physicochemical characteristics (size distribution and zeta-potential) of the
      liposomal formulations and the thermal effects on leuprolide in model lipidic
      bilayers composed of dipalmitoylphosphatidylcholine were studied using
      differential scanning calorimetry. Finally, the dynamic effects of leuprolide in
      an egg phosphatidylcholine/cholesterol system were examined using solid state 13C
      MAS NMR spectroscopy.

PMID- 15942936
TI  - New drug-resistant cassettes for gene disruption and epitope tagging in
      Schizosaccharomyces pombe.
AB  - We describe new heterologous modules for PCR-based gene targeting in the fission
      yeast Schizosaccharomyces pombe. Two bacterial genes, hph and nat, which display
      dominant drug-resistance phenotypes, are used as new selectable markers in these
      modules. Both genes have been used successfully in the budding yeast
      Saccharomyces cerevisiae, in which hph confers resistance to hygromycin B, while
      nat confers nourseothricin resistance (Goldstein and McCusker, 1999). Vector
      modules for gene disruption and C-terminal tagging with 3HA, 13Myc and GFP(S65T)
      are constructed using previously constructed pFA6a-MX6-derived plasmids (Bahler
      et al., 1998; Wach et al., 1997). In combination with the existing systems that
      are based upon the G418-resistance gene (kan), triple gene deletions or tags
      could be constructed. In addition a vector for one-step integration of a
      monomeric RFP (mRFP) to the C-terminus of proteins of interest is developed.
      Finally, oligonucleotides that allow a simple marker switch from kan to hph or
      nat, and vice versa, are described. The new constructs developed here should
      facilitate post-genomic molecular analysis of protein functions in fission yeast.

PMID- 15942937
TI  - Effects of a memory enhancing peptide on cognitive abilities of brain-lesioned
      mice: additivity with huperzine A and relative potency to tacrine.
AB  - Alzheimer's disease (AD) and related dementing disorders having cognitive
      manifestations represent an increasing threat to public health. In the present
      study, the effects of a memory enhancing NLPR tetra-peptide (MEP), huperzine A
      (Hup A), or a combination of the two on the cognitive abilities of brain-lesioned
      mice were evaluated and compared with tacrine in the passive avoidance and Y
      water maze tests for the acquisition and retention aspects of cognitive
      functions. MEP at microg kg(-1) doses, and Hup A or tacrine at mg kg(-1) doses
      significantly reversed the cognition deficits induced by scopolamine. For
      acquisition ability, it was observed that mice administered with MEP (4.0 microg
      kg(-1)) spent less time escaping onto the platform in the water maze than those
      treated with tacrine (1.5 mg kg(-1)); whereas for memory retention, tacrine
      administration resulted in a higher step-through latency in mice at the tested
      dose regime. In addition, co-administration of MEP (2.0 microg kg(-1)) and Hup A
      (0.1 mg kg(-1)) exhibited an additive effect resulting in considerable
      improvements in both acquisition and retention abilities of brain-lesioned mice.
      The results demonstrated that MEP was highly efficient in the rescue of cognitive
      abilities of brain-lesioned mice and in particular, the effective doses of MEP
      were about two orders of magnitude lower than that of tacrine, a therapeutic
      currently used in the treatment of AD. Moreover, MEP and Hup A were effective at
      reduced doses when the two were co-administered, providing a rationale for their
      combined usage in the treatment of cognitive deficits.

PMID- 15942938
TI  - Evidence for a single-step mechanism in the origin of hyperdiploid childhood
      acute lymphoblastic leukemia.
AB  - High hyperdiploidy (>50 chromosomes) in childhood acute lymphoblastic leukemia
      (ALL) is characterized by nonrandom multiple trisomies and tetrasomies involving
      in particular chromosomes X, 4, 6, 8, 10, 14, 17, 18, and 21. This characteristic
      karyotypic pattern, the most common in pediatric ALL, may arise via a tetraploid
      state with subsequent loss of chromosomes, by sequential gains of chromosomes in
      consecutive cell divisions, or by simultaneous gain of chromosomes in a single
      mitosis. These alternatives may be distinguished by investigation of the allelic
      ratios of loci on the tetrasomic and disomic chromosomes. Previous studies of
      tetrasomy 21 and of the occurrence of uniparental disomies (UPDs) have suggested
      that the most likely mechanism is simultaneous gain. However, the other pathways
      have not been definitely excluded because complete analyses of all disomies and
      tetrasomies have never been performed. In the present study, we investigated 27
      hyperdiploid ALLs by using 58 polymorphic microsatellite markers mapped to 23 of
      the 24 human chromosomes. Twenty-six tetrasomies were analyzed (involving
      chromosomes X, 8, 10, 14, 18, and 21), and the frequency of UPDs was determined
      in 10 cases. In total, 200 chromosomes were studied. Equal allele dosage was
      observed in 24 of 26 tetrasomies, and only 7 UPDs were found. These data strongly
      suggest that hyperdiploidy in childhood ALL generally arises by a simultaneous
      gain of all additional chromosomes in a single abnormal mitosis.

PMID- 15942939
TI  - Molecular characterization of the spectrum of genomic deletions in the mismatch
      repair genes MSH2, MLH1, MSH6, and PMS2 responsible for hereditary nonpolyposis
      colorectal cancer (HNPCC).
AB  - A systematic search by Southern blot analysis in a cohort of 439 hereditary
      nonpolyposis colorectal cancer (HNPCC) families for genomic rearrangements in the
      main mismatch repair (MMR) genes, namely, MSH2, MLH1, MSH6, and PMS2, identified
      48 genomic rearrangements causative of this inherited predisposition to
      colorectal cancer in 68 unrelated kindreds. Twenty-nine of the 48 rearrangements
      were found in MSH2, 13 in MLH1, 2 in MSH6, and 4 in PMS2. The vast majority were
      deletions, although one previously described large inversion, an intronic
      insertion, and a more complex rearrangement also were found. Twenty-four deletion
      breakpoints have been identified and sequenced in order to determine the
      underlying recombination mechanisms. Most fall within repetitive sequences,
      mainly Alu repeats, in agreement with the differential distribution of deletions
      between the MSH2 and MLH1 genes: the higher number and density of Alu repeats in
      MSH2 corresponded with a higher incidence of genomic rearrangement at this
      disease locus when compared with other MMR genes. Long interspersed nuclear
      element (LINE) repeats, relatively abundant in, for example, MLH1, did not seem
      to contribute to the genesis of the deletions, presumably because of their older
      evolutionary age and divergence among individual repeat units when compared with
      short interspersed nuclear element (SINE) repeats, including Alu repeats.
      Moreover, Southern blot analysis of the introns and the genomic regions flanking
      the MMR genes allowed us to detect 6 novel genomic rearrangements that left the
      coding region of the disease-causing gene intact. These rearrangements comprised
      4 deletions upstream of the coding region of MSH2 (3 cases) and MSH6 (1 case), a
      2-kb insertion in intron 7 of PMS2, and a small (459-bp) deletion in intron 13 of
      MLH1. The characterization of these genomic rearrangements underlines the
      importance of genomic deletions in the etiology of HNPCC and will facilitate the
      development of PCR-based tests for their detection in diagnostic laboratories.

PMID- 15942940
TI  - Oncogene amplification in the proximal part of chromosome 6 in rat endometrial
      adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo
      FISH, and allelotyping.
AB  - The inbred BDII rat is a valuable experimental model for the genetic analysis of
      endometrial adenocarcinoma (EAC). One common aberration detected by comparative
      genomic hybridization in rat EAC was gain/amplification affecting the proximal
      part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting
      probes onto tumor cell metaphase preparations in order to detect and characterize
      gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by
      fluorescence in situ hybridization with probes representing 12 cancer-related
      genes in the region. The analysis revealed that seven tumors contained large RNO6
      derived homogeneously staining regions (HSRs) in addition to several normal or
      near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited
      a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with
      moderate amplification of one or a few genes. Most commonly, the amplification
      affected the region centered around band 6q16 and included the Mycn, Ddx1, and
      Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected
      by gene amplification but to a lesser extent. The aberrations in the proximal
      part of RNO6 were further analyzed using allelotyping of microsatellite markers
      in all tumors from animals that were heterozygous in the proximal RNO6 region. We
      could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which
      were in addition to those already analyzed by molecular cytogenetic methods as
      described. Our findings suggest that increase/amplification of genes in this
      chromosome region contribute to the development of this hormone-dependent tumor.

PMID- 15942941
TI  - Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced pulmonary
      adenocarcinomas in Syrian golden hamsters contain beta 2-adrenergic receptor
      single-nucleotide polymorphisms.
AB  - Cigarette smoking contributes to the development of lung cancer throughout the
      world, with cases of pulmonary adenocarcinoma (PAC) the most numerous.
      Nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is formed
      from nicotine, has been demonstrated to cause mutations in genes that affect cell
      regulation and proliferation. Moreover, NNK has been shown to interact directly
      with and stimulate beta adrenergic receptor (ADRB) signal transduction pathways.
      Our goal was to determine whether single-nucleotide polymorphisms (SNPs) in the
      Adrb2 from PAC tumors were induced in golden hamsters by the injection of NNK.
      Here we report the cloning and sequencing of Adrb2 clones from either dissected
      lung tumors from NNK-injected animals or whole-lung tissue from water-injected
      controls. Both sets of animals contained SNPs; however, we found significantly
      more SNPs in the Adrb2 from NNK-injected animals than in the controls. The
      majority of these SNPs were novel, nonsynonymous mutations found in regions of
      the Adrb2 known to be involved in ligand binding, G-protein coupling, and
      desensitization/down-regulation. Our data verified the mutagenic effects of NNK
      as well as demonstrated that this animal model provides an outstanding way of
      identifying mutations not only in the Adrb2, but also in other genes that may
      play essential roles in the regulation and growth of pulmonary adenocarcinomas.

PMID- 15942942
TI  - PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL
      with complex chromosomal rearrangements.
AB  - We present an extensive characterization of 10 B-cell lymphomas with a
      t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was
      demonstrated by fluorescence in situ hybridization (FISH) using a validated probe
      set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M
      FISH). Pathologic and clinical review revealed the presence of this rearrangement
      in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2
      posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to
      initial observations describing this translocation in lymphoplasmacytic lymphoma
      (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic
      and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an
      association between this aberration and a subset of de novo DLBCLs presenting
      with advanced disease and adverse prognosis. In addition, the recurrent incidence
      of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was
      previously unrecognized and is intriguing.

PMID- 15942943
TI  - Familial occurrence of thymoma and autoimmune diseases with the constitutional
      translocation t(14;20)(q24.1;p12.3).
AB  - Thymomas are low-grade epithelial cancers of the thymus whose prevalence varies
      between 0.1/100,000 and 0.4/100,000. Familial occurrence of thymoma is very rare.
      We studied a family bearing the constitutional chromosome translocation
      t(14;20)(q24;p12), 3 of whose members had a thymoma. In this family, among 27
      patients, 11 had the translocation: 3 had thymoma and 4 others had 5 different
      autoimmune diseases: type 1 diabetes mellitus, Graves' disease, pernicious
      anemia, primitive Sjogren disease, and autoimmune pancytopenia. FISH studies
      allowed us to be more specific about the translocation breakpoints. The 14q24
      breakpoint was in intron 5 of RAD51L1, and the 20p12 breakpoint was 100 kb
      telomeric to BMP2. RAD51L1 is a tumor-suppressor gene belonging to the RAD51
      family, already implicated in many tumors (uterine leiomyomas, pseudo-Meigs
      syndromes, pulmonary chondroid hamartomas) and involved in recombinational repair
      of DNA double-strand breaks. BMP2 belongs to the TGFbeta superfamily, and the
      BMP2-BMP4 genes are involved in thymocyte differentiation by blocking progression
      from CD4-CD8- to CD4+CD8+ while maintaining a sufficient pool of immature
      precursors. Dysregulation of RAD51L1 and/or BMP2 may explain this familial
      occurrence of thymomas and autoimmune diseases. Using QRT-PCR, we studied the
      expression of BMP2 in 20 sporadic thymomas and found various levels of expression
      that may be associated with autoimmune diseases.

PMID- 15942944
TI  - Atypical interhemispheric fusion with a cebocephalic-like functional single
      nostril nose and a novel SHH mutation.

PMID- 15942945
TI  - Cerebro-oculo-nasal syndrome, a disorder with some manifestations suggestive of
      the holoprosencephalic spectrum: new case and imaging review of previous cases.

PMID- 15942946
TI  - CNS findings in three cases of septo-optic dysplasia, including one with
      semilobar holoprosencephaly.

PMID- 15942947
TI  - Central nervous system malformations in oral-facial-digital syndrome, type 1.

PMID- 15942948
TI  - Newly recognized overgrowth syndrome with macrosomia, macrocrania, hyperostosis
      of the cranial vault, mental deficiency, seizures, poor motor control, and
      orofacial dyspraxia.

PMID- 15942949
TI  - Specific interaction of chalcone-protein: cardamonin binding site II on the human
      serum albumin molecule.
AB  - Cardamonin (2',4'-dihydroxy-6'-methoxychalcone), one of the main constituents
      from the seeds of Alpinia katsumadai Hayata, belongs to chalcone with its
      antibacterial, antiinflammatory and other important therapeutic activities of
      significant potency and low systemic toxicity. In this article, the interaction
      of cardamonin to human serum albumin (HSA) has been studied for the first time by
      spectroscopic methods including Fourier transform infrared (FTIR) spectroscopy,
      circular dichroism (CD), and UV-absorption spectroscopy in combination with
      fluorescence quenching under physiological conditions with drug concentrations of
      0.67-4.0 microM. The results of the spectroscopic measurements and the
      thermodynamic parameters obtained (the enthalpy change DeltaH(0) and the entropy
      change DeltaS(0) were calculated to be -25.312 and 7.040 J.mol(-1).K(-1)
      according to the van't Hoff equation) suggest that hydrophobic interaction is the
      predominant intermolecular forces stabilizing the complex, which is also in good
      agreement with the results of the molecule modeling study. The alterations of
      protein secondary structure in the presence of cardamonin in aqueous solution
      were quantitatively calculated by the evidence from CD and FTIR spectroscopes
      with reductions of alpha-helices of about 20%, decreases of beta-sheet structures
      of about 14%, and increases of beta-turn structures of about 15%. The quenching
      mechanism and the number of binding sites (n approximately 1) were obtained by
      fluorescence titration data. Fluorescent displacement measurements confirmed that
      cardamonin binds HSA on site II. In addition, the effects of common ions on the
      constants of the cardamonin-HSA complex were also discussed.

PMID- 15942950
TI  - Determining the extent of quality health care for hospitalized patients with
      cirrhosis.
AB  - BACKGROUND/AIMS: Since few data are available concerning the clinical course of
      decompensated hepatitis C virus (HCV)-related cirrhosis, the aim of the present
      study was to define the natural long-term course after the first hepatic
      decompensation. METHODS: Cohort of 200 consecutive patients with HCV-related
      cirrhosis, and without known hepatocellular carcinoma (HCC), hospitalized for the
      first hepatic decompensation. RESULTS: Ascites was the most frequent first
      decompensation (48%), followed by portal hypertensive gastrointestinal bleeding
      (PHGB) (32.5%), severe bacterial infection (BI) (14.5%) and hepatic
      encephalopathy (HE) (5%). During follow-up (34+/-2 months) there were 519
      readmissions, HCC developed in 33 (16.5%) patients, and death occurred in 85
      patients (42.5%). The probability of survival after diagnosis of decompensated
      cirrhosis was 81.8 and 50.8% at 1 and 5 years, respectively. HE and/or ascites as
      the first hepatic decompensation, baseline Child-Pugh score, age, and presence of
      more than one decompensation during follow-up were independently correlated with
      survival. CONCLUSIONS: Once decompensated HCV-related cirrhosis was established,
      patients showed not only a very high frequency of readmissions, but also
      developed decompensations different from the initial one. These results
      contribute to defining the natural course and prognosis of decompensated HCV
      related cirrhosis.

PMID- 15942951
TI  - Seven letters to the editor reporting new findings in patients with
      holoprosencephaly.

PMID- 15942952
TI  - SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a
      solitary median maxillary incisor.

PMID- 15942953
TI  - Single median maxillary central incisor, hypophyseal tumor, and SHH mutation.

PMID- 15942954
TI  - Cementum on Smilodon sabers.
AB  - The maxillary canines of Smilodon californicus Bovard, 1907 have a deeply curved
      cementoenamel junction. The gingiva of modern cats is attached to the tooth at
      the cementoenamel junction and provides tactile and other dental information to
      the animal. The presence of cementum at the cervix of the maxillary canines, also
      called sabers, would indicate that the gingiva in Smilodon was attached in this
      region. Such an attachment would be advantageous, providing stability and sensory
      input for the large tooth. Also, gingiva at the cervix would impact the manner in
      which the teeth were used. Previous study using scanning electron microscopy of
      dental casts was indirect. The purpose of this study was to confirm by direct
      methods the presence of cementum at the cervix of Smilodon californicus sabers.
      Parts of three Smilodon californicus sabers were sectioned and examined with
      light and scanning electron microscopy (EDS). In addition, percent weight of
      calcium and phosphorus was measured in enamel, dentin, and cementum using
      electron dispersive spectroscopy. Cementum was identified in the cervical region
      of each saber. Spectroscopy confirmed that the tissue is calcified and the
      mineral is hydroxyapatite. Percent calcium and percent phosphorus of individual
      tissues were highly variable between specimens. However, the ratios of calcium to
      phosphorus were not significantly different from the hydroxyapatite standard. In
      the future, bite models will have to take the presence of soft tissues into
      account.

PMID- 15942955
TI  - Architecture and mineralization of developing trabecular bone in the pig
      mandibular condyle.
AB  - Architecture and mineralization are important determinants of trabecular bone
      quality. To date, no quantitative information is available on changes in
      trabecular bone architecture and mineralization of newly formed bone during
      development. Three-dimensional architecture and mineralization of the trabecular
      bone in the mandibular condyle from six pigs of different developmental ages were
      investigated with micro-CT. Anteriorly in the condyle, a more advanced state of
      remodeling was observed than posteriorly, where more active growth takes place.
      Posteriorly, the bone volume fraction increased with age (r=0.87; P<0.05) by an
      increase of trabecular thickness (r=0.88; P<0.05), while the number of trabeculae
      declined (r=-0.86; P<0.05). Anteriorly, despite an increase in trabecular
      thickness (r=0.97; P<0.001), there was no change in bone volume fraction due to a
      simultaneous decline in trabecular number (r=-0.84; P<0.05) and increase in
      trabecular separation (r=0.95; P<0.01). Posteriorly, rods were remodeled into
      plates as expressed by the structure model index (r=-0.97; P<0.001), whereas
      anteriorly, a plate-like structure was already present in early stages. The
      trabecular structure had a clear orientation throughout the developmental
      process. The global degree of mineralization increased both anteriorly (r=0.86;
      P<0.05) and posteriorly (r=0.89; P<0.05). We suggest that the degree of
      mineralization does not depend on the bone volume, but on the thickness of the
      trabeculae as the mineralized centers of trabeculae were getting larger and more
      highly mineralized with age compared to their appositional layers. This indicates
      that besides apposition of new bone material on the surface of trabeculae, the
      mineralized tissue in their centers still changes and matures.

PMID- 15942956
TI  - Central diabetes insipidus: Is it Langerhans cell histiocytosis of the pituitary
      stalk? A diagnostic pitfall.
AB  - Central diabetes insipidus (CDI) is a rare disorder that may be caused by a
      variety of diseases. In pediatric and adolescent patients the most common causes
      for CDI are Langerhans cell histiocytosis (LCH) and germinoma. To avoid a
      potentially hazardous biopsy of the hypothalamic pituitary region it is
      recommended to evaluate patients with CDI carefully to identify potential
      extracranial lesions. Since LCH is the most common systemic disease that may
      cause CDI, special focus is paid to the identification of LCH lesions. We report
      on a 9(1/2) year old girl who presented with central diabetes insipidus and a
      thickening of the pituitary stalk on magnetic resonance imaging. Diagnostic
      workup revealed a history of recurrent ear infections and a compressed 6th
      thoracic vertebral body on radiographs. Based on these findings LCH was
      anticipated. Upon growth of the pituitary stalk lesion the patient was treated
      with LCH standard chemotherapy. After an initial shrinkage of the lesion, a
      further growth of the pituitary stalk lesion was observed and the tumor was
      resected. Histopathology revealed germinoma. This case underscores the importance
      of a istopathologically proven diagnosis in patients with HPR tumors before the
      initiation of a specific therapy, even if the clinical findings are highly
      suggestive.

PMID- 15942958
TI  - Proteomics profiling of nuclear proteins for kidney fibroblasts suggests hypoxia,
      meiosis, and cancer may meet in the nucleus.
AB  - Proteomics methods were used to characterize proteins that change their form or
      abundance in the nucleus of NRK49F rat kidney fibroblasts during prolonged
      hypoxia (1% O(2), 12 h). Of the 791 proteins that were monitored, about 20%
      showed detectable changes. The 51 most abundant proteins were identified by mass
      spectrometry. Changes in nuclear receptor transcription factors (THRalpha1,
      RORalpha4, HNF4alpha, NUR77), other transcription factors (GATA1, AP-2alpha,
      OCT1, ATF6alpha, ZFP161, ZNF354A, PDCD2), and transcription cofactors (PC4, PCAF,
      MTA1, TCEA1, JMY) are indicative of major, co-ordinated changes in transcription.
      Proteins involved in DNA repair/recombination, ribosomal RNA synthesis, RNA
      processing, nuclear transport, nuclear organization, protein translation,
      glycolysis, lipid metabolism, several protein kinases (PKCdelta, MAP3K4, GRK3),
      as well as proteins with no established functional role were also observed. The
      observed proteins suggest nuclear regulatory roles for proteins involved in
      cytosolic processes such as glycolysis and fatty acid metabolism, and roles in
      overall nuclear structure/organization for proteins previously associated with
      meiosis and/or spermatogenesis (synaptonemal complex proteins 1 and 2 (SYCP1,
      SYCP2), meiosis-specific nuclear structural protein 1 (MNS1), LMNC2, zinc finger
      protein 99 (ZFP99)). Proteins associated with cytoplasmic membrane functions
      (ACTN4, hyaluronan mediated motility receptor (RHAMM), VLDLR, GRK3) and/or
      endocytosis (DNM2) were also seen. For 30% of the identified proteins, new
      isoforms indicative of alternative transcription were detected (e.g., GATA1,
      ATF6alpha, MTA1, MLH1, MYO1C, UBF, SYCP2, EIF3S10, MAP3K4, ZFP99). Comparison
      with proteins involved in cell death, cancer, and testis/meiosis/spermatogenesis
      suggests commonalities, which may reflect fundamental mechanisms for down
      regulation of cellular function.

PMID- 15942959
TI  - Activity of SPANphos rhodium dimers in methanol carbonylation.

PMID- 15942960
TI  - Nanoparticle PCR: nanogold-assisted PCR with enhanced specificity.

PMID- 15942961
TI  - Bridging phosphanes: exotic or versatile binucleating ligands?

PMID- 15942962
TI  - Multinuclear copper triethanolamine complexes as selective catalysts for the
      peroxidative oxidation of alkanes under mild conditions.

PMID- 15942963
TI  - Prodrug activation gated by a molecular "OR" logic trigger.

PMID- 15942964
TI  - Enantioselective epoxidation of allylic alcohols by a chiral complex of vanadium:
      an effective controller system and a rational mechanistic model.

PMID- 15942965
TI  - Self-assembled vanadium pentoxide (V2O5) hollow microspheres from nanorods and
      their application in lithium-ion batteries.

PMID- 15942966
TI  - Highly enantioselective catalytic fluorination and chlorination reactions of
      carbonyl compounds capable of two-point binding.

PMID- 15942967
TI  - A theoretical study on the low-lying excited states of 2,2':5',2''-terthiophene
      and 2,2':5',2'':5'',2'''-quaterthiophene.
AB  - The nature and properties of the low-lying singlet and triplet valence excited
      states of 2,2':5',2''-terthiophene (terthiophene) and 2,2':5',2'':5'',2'''
      quaterthiophene (tetrathiophene) are discussed on the basis of high-level ab
      initio computations. The spectroscopic features determined experimentally for
      short alpha-oligothiophenes are rationalised on theoretical grounds. Special
      attention is devoted to the nonradiative decay process through intersystem
      crossing (ISC) from the singlet to the triplet manifold, which is known to be
      relatively less efficient in tetrathiophene. Along the geometry relaxation of the
      S1 state of terthiophene, the S1 and T2 states become degenerate, which leads to
      a favourable situation for the occurrence of ISC. The parallel process is
      expected to be less favoured in tetrathiophene because of the less efficient spin
      orbit coupling and the increase of the S1-T2 energy gap.

PMID- 15942968
TI  - The excited-state chemistry of phycocyanobilin: a semiempirical study.
AB  - Based on previous time-resolved absorption studies, phycocyanobilin undergoes a
      photoreaction from an A- into a B- and C-form, with the latter two photoproducts
      showing absorption spectra red-shifted from A. To identify the molecular
      mechanism involved in the excited-state reactions, the structural origin of the
      red shift in the absorption spectra is investigated. Using semiempirical AM1
      calculations that include configuration interaction by pair doubles excitation
      configuration interaction, the absorption spectra of different conformers as well
      as different protonation states were calculated. The results clearly indicate a
      pronounced red shift in the spectra of structures either protonated or
      deprotonated at the basic/acidic centres of the tetrapyrrole chromophore whereas,
      in contrast, conformational changes alone result in a blue shift. Furthermore, it
      is shown by quantum chemical calculations that the basicity of phycocyanobilin is
      much higher in the excited than in the ground state, with a decrease in the
      excited-state pK(B)* of approximately 9.5 units. The acidity is only slightly
      enhanced with a drop in pK(A)* of only approximately 1.6 units. From these
      findings, a reaction model for the excited-state processes in phycocyanobilin is
      proposed. According to this model, photoexcitation of phycocyanobilin triggers an
      excited-state proton transfer giving rise to the formation of a protonated
      species. In parallel, the local increase in the medium pH associated with
      protonation then forwards a deprotonation at an acidic NH-group so that in effect
      both protonated and deprotonated phycocyanobilin would arise from the initial
      photoreaction and account for the observed red shift in the spectra of the B- and
      C-forms.

PMID- 15942969
TI  - A counter based on the electrical input/output stimuli activation of an array of
      quantum dots.

PMID- 15942970
TI  - Cooperativity and proton transfer in hydrogen-bonded triads.
AB  - Ab initio MP2/6-311+G(3df,2pd) and MP2/aug-cc-pVTZ calculations have been carried
      out to investigate the structures and properties of AHXHYH(3) (A=F, Cl; X=F, Cl;
      Y=N, P) hydrogen-bonded complexes. Significant cooperative effects are observed
      in the XHYH3 dyads in the triads due to the presence of the polar near-neighbor
      AH. These effects are greater when the polar partner is HF, which is a better
      proton donor than HCl. Structural changes, red shifts of proton-donor stretching
      frequencies, nonadditive interaction energies, and electron density
      redistributions unambiguously demonstrate that the X--HY hydrogen bond (HB) is
      stronger in the triads than in the corresponding dyads, while the X--H bond of
      the proton donor becomes weaker. Even more pronounced cooperative effects are
      observed in the AHXH dyads due to the presence of the YH3 partner. These effects
      are weaker in complexes having PH3 rather than NH3 as the proton acceptor, since
      NH3 is a stronger base. Cooperativity also enhances the proton-donating ability
      of the YH3 moiety, with the result that all complexes except FHFHPH3 are cyclic.
      Cooperativity, together with the ease of breaking the Cl--H bond in ClHClHNH3 and
      FHClHNH3, leads to proton transfer (PT), so that these two complexes are better
      described as approaching hydrogen-bonded ClHCl- x +HNH3 and FHCl- x +HNH3 ion
      pairs.

PMID- 15942971
TI  - Synthesis and optical properties of silver nanoparticles and arrays.
AB  - This Minireview systematically examines optical properties of silver
      nanoparticles as a function of size. Extinction, scattering, and absorption cross
      sections and distance dependence of the local electromagnetic field, as well as
      the quadrupolar coupling of 2D assemblies of such particles are experimentally
      measured for a wide range of particle sizes. Such measurements were possible
      because of the development of a novel synthetic method for the size-controlled
      synthesis of chemically clean, highly crystalline silver nanoparticles of narrow
      size distribution. The method and its unique advantages are compared to other
      methods for synthesis of metal nanoparticles. Synthesis and properties of
      nanocomposite materials using these and other nanoparticles are also described.
      Important highlights in the history of the field of metal nanoparticles as well
      as an examination of the basic principles of plasmon resonances are included.

PMID- 15942972
TI  - Voltammetric sizing of inert particles.
AB  - The average size of inert particles is determined using a simple electrochemical
      procedure. Alumina particles are deposited on an edge-plane graphite electrode,
      and a cyclic voltammogram is recorded. The scan rate employed varies between 0.2
      and 2 V s(-1). At these scan rates the diffusion layer thickness is greater than
      the size of the alumina particles, minimizing the influence of the particles'
      height on the observed voltammetry. The average size of the particles is
      determined via comparison of the experimental voltammograms with simulations.

PMID- 15942973
TI  - Efficiency in nonenzymatic kinetic resolution.
AB  - The Walden memorial at the Technical University in Riga is pictured in the
      frontispiece to mark the recent centennial of the Walden inversion. This is a
      rare public monument to key events from the first era of exploration in
      stereocontrolled synthesis, and may be the only such monument to use the language
      of organic chemistry expressed at the molecular level. The reaction of racemic
      substrates with chiral nucleophiles is one of many methods currently known to
      achieve kinetic resolution, a phenomenon that ranks as the oldest and most
      general approach for the synthesis of highly enantioenriched substances. The
      first nonenzymatic kinetic resolutions as well as the original forms of the
      Walden inversion were studied in the 1890s. All of these investigations were
      conducted within the first generation following the demonstration that carbon is
      tetrahedral, and provided abundant evidence that the principles and importance of
      enantiocontrolled syntheses were understood. However, a reliable, rapid technique
      to quantify results and guide the optimization process was still lacking. Many
      decades passed before this problem was solved by the advent of HPLC and GLPC
      assays on chiral supports, which stimulated explosive growth in the synthesis of
      nonracemic substances by kinetic resolution. The Walden monument is accessible to
      passers-by for hands-on inspection as well as for contemplation and learning. In
      a similar way, kinetic resolution is experimentally accessible and can be thought
      provoking at several levels. We follow the story of kinetic resolution from the
      early discoveries through fascinating historical milestones and conceptual
      developments, and close with a focus on modern techniques that maximize
      efficiency.

PMID- 15942974
TI  - Synthesis of a cycloallin derivative from beta-cyclodextrin: heptakis(2,3-dideoxy
      2,3-epithio)-beta-cycloallin.

PMID- 15942975
TI  - Supramolecular assembly and coordination-assisted deaggregation of multimetallic
      macrocycles.

PMID- 15942976
TI  - Esters of 6-aminohexanoic acid as skin permeation enhancers: The effect of
      branching in the alkanol moiety.
AB  - In order to investigate the effect of branching and cyclization in the
      hydrophobic part of skin permeation enhancers, 17 novel branched-chain and cyclic
      6-aminohexanoic acid esters were prepared. Their permeation enhancing activity
      was evaluated in vitro using human skin and theophylline as a model drug, and
      compared to that of the corresponding linear-chain analogues. The results showed
      that chain branching and cyclization has a negative influence on the enhancing
      activity of 6-aminohexanoates. For example, the enhancement ratios (ERs) of
      dodecan-1-yl, dodecan-2-yl, dodecan-4-yl, and cyclododecyl ester were 39.7, 29.3,
      3.1, and 2.2, respectively. No significant change in the optimum length of the
      chain was observed. Dodecan-2-yl 6-aminohexanoate, the most active branched
      derivative, still maintains a remarkable enhancing activity (ER 29.3).
      Presumably, the relatively small degree of branching of these molecules does not
      prevent them from interacting with the lipid components of the stratum corneum.
      However, a higher degree of branching, cyclization of the chain, and presence of
      an aromatic ring resulted in a loss of activity.

PMID- 15942977
TI  - Risk selection in the German public health insurance system.
AB  - The German statutory health insurance market was exposed to competition in 1996.
      To limit direct risk selection the regulator required open enrollment. As the
      risk compensation scheme, introduced in 1994, is highly incomplete, substantial
      incentives for risk selection exist. Due to their low premiums, company-based
      sickness funds have been able to attract a lot of new members. We analyze, using
      data from the German Socio-Economic Panel, the determinants of switching behavior
      from 1995 to 2000. There is no evidence for selection by funds. The success of
      the company-based sickness funds originates in incomplete risk adjustment
      together with the negative correlation between health status and switching costs.

PMID- 15942978
TI  - Human papillomavirus type 16 in head and neck carcinogenesis.
AB  - The aetiology of squamous cell carcinomas of the head and neck (HNSCC) is
      multifactorial. Oncogenic human papillomaviruses (HPVs), a causative agent in
      uterine cervical cancer, have also been repeatedly detected in HNSCC, especially
      in squamous cell carcinomas of tonsils. Approximately half the HPV DNA-positive
      HNSCC contain detectable E6/E7 transcripts with wild-type p53, reduced pRb and
      overexpressed p16 in the tumours. HPV-16 is the predominant type and exists in
      episomal, integrated, or mixed forms. Tonsillar carcinomas have a remarkably
      higher viral load than carcinomas at other sites of the head and neck region. HPV
      16 DNA has also been detected in tumour-free tonsils. Infection by oncogenic HPVs
      is a necessary but not a sufficient cause of cancers. Studies on the molecular
      mechanisms underlying HPV-associated carcinogenesis are difficult, because HPV is
      not easy to propagate in vitro. HPV-immortalised human tonsillar epithelial cell
      lines may provide an in vitro model to study co-factors for the HPV-associated
      tonsillar cancers and to test the effects of anti-viral and anti-tumour agents.

PMID- 15942979
TI  - The host environment drives HIV-1 fitness.
AB  - Viral fitness is defined by the ability of an individual genotype to produce
      infectious progeny in a specific environment. For HIV the environment is never
      constant but rather fluctuates in time and space. For instance, environmental
      factors that determine viral fitness during transmission from host to host are
      different to the pressures from either cytotoxic T-lymphocytes (CTLs) or
      antiviral drugs. Consequently, viral fitness is highly dependent on the
      environment and the accurate determination of this value therefore depends
      strongly on the chosen environmental setting. This review describes how the host
      environment imposes selective pressures on the virus that shape its genotype and
      fitness. The most important environments that the virus encounters throughout its
      life cycle and during natural infection are discussed. In order of appearance,
      CTLs are discussed, followed by neutralising antibodies and antiretroviral drug
      treatment. It then goes on to describe receptor molecules that mediate viral
      entry and intracellular restriction factors, which represent selective pressures
      that are present directly from the start of a natural infection. It concludes by
      discussing the complexity of viral fitness and how an accurate measure of viral
      fitness eventually may, for example, contribute to the improvement of
      antiretroviral therapy or help in the formulation of an optimal vaccination
      strategy.

PMID- 15942980
TI  - Regulation versus practice--the impact of accessibility on the use of specialist
      health care in Norway.
AB  - In Norway specialized health services are provided both by public hospitals and
      by privately practicing specialists who have a contract with the public sector. A
      patient's co-payment is the same irrespective of the type of provider he visits.
      The ambition of equity in the allocation of medical care is high among all
      political parties. The instruments for auditing whether these goals are fulfilled
      are not equally ambitious. The objective of the present study is to explore
      whether laws and regulations that govern the allocation of specialist health care
      resources in fact are fulfilled. Panel data from the Survey of Living Conditions
      are merged with data on capacity and spatial access to primary and specialist
      care. We find that accessibility and socio-economic variables play a considerable
      role in determining both the probability of at least one visit and the number of
      visits to a private specialist. A person with a higher university degree living
      in a municipality with the highest value of the geographical accessibility index
      has a 46%-points higher probability of at least one visit to a private specialist
      compared with a person with junior high living in a municipality with the lowest
      value of the accessibility index. With regard to visits to a hospital outpatient
      department these variables are not found to have significant effects. We conclude
      that public ambitions and regulations are fulfilled for specialist services
      provided by public hospitals. With regard to the provision of services provided
      by publicly financed private specialists we find a discrepancy between public
      goals and surveyed practice.

PMID- 15942981
TI  - An investigation into the empirical validity of the EQ-5D and SF-6D based on
      hypothetical preferences in a general population.
AB  - BACKGROUND: An important consideration for studies that derive utility scores
      using multi-attribute utility measures is the psychometric integrity of the
      measurement instrument. Of particular importance is the requirement to establish
      the empirical validity of multi-attribute utility measures; that is, whether they
      generate utility scores that, in practice, reflect people's preferences. We
      compared the empirical validity of EQ-5D versus SF-6D utility scores based on
      hypothetical preferences in a large, representative sample of the English
      population. METHODS: Adult participants in the 1996 Health Survey for England
      (n=16 443) formed the basis of the investigation. The subjects were asked to
      complete the EQ-5D and SF-36 measures. Their responses were converted into
      utility scores using the York A1 tariff set and the SF-6D utility algorithm,
      respectively. One-way analysis of variance was used to test the hypothetically
      constructed preference rule that each set of utility scores differs significantly
      by self-reported health status (categorised as very good, good, fair, bad or very
      bad). The degree to which EQ-5D and SF-6D utility scores reflect alternative
      configurations of self-reported health status; illness, disability or infirmity,
      and medication use was tested using the relative efficiency statistic and
      receiver operating characteristic (ROC) curves. RESULTS: The mean utility score
      for the EQ-5D was 0.845 (95% CI: 0.842, 0.849), whilst the mean utility score for
      the SF-6D was 0.799 (95% CI: 0.797, 0.802), representing a mean difference in
      utility score of 0.046 (95% CI: 0.044, 0.049; p<0.001). Bland-Altman plots
      displayed considerable lack of agreement between the two measures, particularly
      at the lower end of the utility scale. Both measures demonstrated statistically
      significant differences between subjects who described their health status as
      very good, good, fair, bad or very bad (p<0.001), as well as monotonically
      decreasing utility scores (test for linear trend: p<0.001). The SF-6D was between
      30.9 and 100.4% more efficient than the EQ-5D at detecting differences in self
      reported health status, and between 10.4 and 45.6% more efficient at detecting
      differences in illness, disability or infirmity and medication use. The area
      under the curve scores generated by the ROC curves were significantly higher for
      the SF-6D at the 0.1% significance level when self-reported health status was
      dichotomised as very good versus good, fair, bad or very bad. However, the AUC
      scores did not reveal any significant differences in the discriminatory powers of
      the measures when alternative configurations of illness, disability or infirmity
      and medication use were examined. CONCLUSIONS: This study provides evidence that
      the SF-6D is an empirically valid and efficient alternative multi-attribute
      utility measure to the EQ-5D, and is capable of discriminating between external
      indicators of health status. However, health economists should also consider
      other psychometric properties, such as practicality and reliability, when
      selecting either measure for evaluative purposes.

PMID- 15942982
TI  - India's strategy to bridge the public-private divide.

PMID- 15942983
TI  - The role of competitive intelligence in biotech startups.

PMID- 15942985
TI  - Abstracts of the 44th Annual Meeting of the Society of Toxicology. New Orleans,
      Louisiana, USA, March 6-10, 2005.

PMID- 15942984
TI  - Abstracts of the 8th European College of Neuropsychopharmacology (ECNP) Regional
      Meeting. Moscow, Russia, April 14-16, 2005.

PMID- 15942986
TI  - Patient notification exercise following a dentist's admission of the periodic use
      of unsterilized equipment.
AB  - During 2001, Greater Glasgow National Health Service (NHS) Board undertook a
      patient notification exercise in a Glasgow dental practice following the
      admission, by the dentist, of the use of unsterilized dental equipment on
      patients. Four thousand and eighty-nine exposed patients were identified; of
      these, 1696 contacted the NHS helpline and 1005 were counselled and screened for
      hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency
      virus. One patient showed evidence of previous HBV infection and 13 had
      antibodies to HCV. Molecular investigation of the HCV isolates indicated no
      significant associations. The investigation found no evidence of patient-to
      patient transmission of HCV among patients attending the practice of a dentist
      who admitted periodically using unsterilized equipment.

PMID- 15942987
TI  - National infection control initiatives within countries of the southern and
      eastern Mediterranean.

PMID- 15942988
TI  - Investigations of the solvent polarity effect on the photophysical properties of
      coumarin-7 dye.
AB  - Photophysical investigations of coumarin-7 (C7) dye in different solvents using
      absorption, steady-state fluorescence and time-resolved fluorescence measurements
      reveal the behavioral changes of the dye in nonpolar and other solvents. In
      moderate to higher polarity solvents, the experimental parameters such as
      fluorescence quantum yield (Phif), fluorescence lifetime (tauf), radiative rate
      constant (k(f)), nonradiative rate constant (k(nr)) and Stokes' shift (Deltav)
      follow almost linear correlations with the Lippert-Mataga solvent polarity
      parameter Deltaf but show unusual deviations in nonpolar solvents. From the
      observed results, it is inferred that the dye exists in a planar intramolecular
      charge transfer structure in moderate to higher polarity solvents, but in
      nonpolar solvents, the dye exists in a nonplanar structure with its 7-NEt2 group
      adopting a pyramidal type of configuration. Unlike some of the other coumarin
      dyes, namely coumarin-120 (C120) (4-CH3-7-NH2-1,2-benzopyrone) and coumarin-151
      (C151) 4-CF3-7-NH2-1,2-benzopyrone), which also show similar structural changes
      in nonpolar and other solvents, the C7 dye does not show any activation
      controlled deexcitation process in nonpolar solvents. This is attributed to the
      very slow flip-flop motion of the 7-NEt2 group of the C7 dye in comparison with
      the very fast flip-flop motion of the 7-NH2 group in the C120 and C151 dyes.
      Qualitative potential energy diagrams are presented to rationalize the observed
      results of C7 dye and to compare these with those of the other dyes such as C120
      and C151. A support for the observed results and interpretation has also been
      obtained from quantum chemical calculations on the structures of the C7 dye.

PMID- 15942989
TI  - [Secreting villous adenoma. Diagnosis and treatment].

PMID- 15942990
TI  - [Acute viral hepatitis].

PMID- 15942991
TI  - Death behind bars.

PMID- 15942992
TI  - [An orally available viral fusion inhibitor found].

PMID- 15942993
TI  - The value of the preoperative visit by an anesthetist. A study of doctor-patient
      rapport.
AB  - The psychologic effect of the preoperative visit by an anesthetist has been
      compared with the effect of pentabarbital for preanesthetic medication. Patients
      receiving pentobarbital 1 hour before an operation became drowsy but it could not
      be shown that they became calm. Patients who had received a visit by an
      anesthetist before operation (informing them about the events which were to occur
      on the day of the operation and about the anesthetic to be administered) were not
      drowsy but were more likely to be calm on the day of the operation. The
      importance of the preoperative visit probably explains, in part, the difficulties
      previous investigators have had in showing sedative effects from barbiturates and
      narcotics before operation. The tremendous emotional significance to a patient of
      illness or an operation may explain why physicians are able to exert such
      influence upon their patients.

PMID- 15942994
TI  - The coming commoditization of processes.
AB  - Despite the much-ballyhooed increase in outsourcing, most companies are in do-it
      yourself mode for the bulk of their processes, in large part because there's no
      way to compare outside organizations' capabilities with those of internal
      functions. Given the lack of comparability, it's almost surprising that anyone
      outsources today. But it's not surprising that cost is by far companies' primary
      criterion for evaluating outsourcers or that many companies are dissatisfied with
      their outsourcing relationships. A new world is coming, says the author, and it
      will lead to dramatic changes in the shape and structure of corporations. A broad
      set of process standards will soon make it easy to determine whether a business
      capability can be improved by outsourcing it. Such standards will also help
      businesses compare service providers and evaluate the costs versus the benefits
      of outsourcing. Eventually these costs and benefits will be so visible to buyers
      that outsourced processes will become a commodity, and prices will drop
      significantly. The low costs and low risk of outsourcing will accelerate the flow
      of jobs offshore, force companies to reassess their strategies, and change the
      basis of competition. The speed with which some businesses have already adopted
      process standards suggests that many previously unscrutinized areas are ripe for
      change. In the field of technology, for instance, the Carnegie Mellon Software
      Engineering Institute has developed a global standard for software development
      processes, called the Capability Maturity Model (CMM). For companies that don't
      have process standards in place, it makes sense for them to create standards by
      working with customers, competitors, software providers, businesses that
      processes may be outsourced to, and objective researchers and standard-setters.
      Setting standards is likely to lead to the improvement of both internal and
      outsourced processes.

PMID- 15942995
TI  - Reducing harm caused by tobacco. Research findings from the University of
      Minnesota.
AB  - Researchers from the University of Minnesota Transdisciplinary Tobacco Use
      Research Center have spent the past 5 years exploring ways to evaluate exposure
      to tobacco toxins in smokers and nonsmokers and reduce the associated health
      risks. This article discusses research into the health effects associated with
      smokers reducing the number of cigarettes they consume and using lower-tar
      cigarettes, modified tobacco products, and smokeless tobacco. Researchers found
      little, if any, benefit to products that promise less exposure to cancer-causing
      tobacco toxins.

PMID- 15942996
TI  - The Childhood Cancer Survivor Study: a resource for research of long-term
      outcomes among adult survivors of childhood cancer.
AB  - Improvements in the treatment of the cancers occurring among children and
      adolescents have resulted in a large number of patients achieving long-term
      survival. Treatment-related factors have been shown to have an impact on
      subsequent health status and quality of life, although there are limited data on
      survivors who are now 2 or more decades past treatment. The Childhood Cancer
      Survivor Study (CCSS) was established as a resource for investigating the long
      term outcomes of a cohort of 5-year survivors of pediatric and adolescent cancer,
      who were diagnosed between 1970 and 1986. The CCSS consists of more than 14,000
      active participants, including survivors of leukemia, brain tumors, Hodgkin's
      disease, non-Hodgkin's lymphoma, Wilms' tumor, neuroblastoma, soft-tissue
      sarcoma, and bone tumors, who have provided self-reported sociodemographicand
      health-related information. The survivor population has been found to be at
      increased risk of a broad spectrum of adverse outcomes, such as late mortality,
      second cancers, pulmonary complications, pregnancy loss, giving birth to
      offspring with low birth weights, and decreased educational attainment. The
      ongoing evaluation of large and diverse cohorts of cancer survivors, through
      resources such as the CCSS, will aid in further identifying high-risk individuals
      who should be the target of innovative intervention strategies.

PMID- 15942997
TI  - Altered gene expression in human cells induced by the agricultural chemical
      Enable.
AB  - Steroid hormones bind to highly specific nuclear receptors, regulating gene
      expression that results in normal fetal growth and development and/or in normal
      adult physiological function. Many industrial and agricultural chemicals may bind
      one or more nuclear receptors, acting as mimics of steroid hormones, and are
      called endocrine disruptive chemicals (EDC) because they alter the expression of
      endocrine-regulated genes. A widely used fungicide, Enable (fenbuconazole), was
      evaluated to examine its capacity to alter endocrine-regulated gene expression.
      Cells of an oestrogen-dependent human breast cancer-derived line, MCF-7, were
      treated with a range, 0.033-3.3 ppb (ng/mL), of Enable, and gene expression was
      compared to that of untreated cells. Microarray analysis using a chip with 600
      gene spots showed downregulation of eight genes and upregulation of 34 genes in
      cells treated with 3.3 ppb of Enable, compared to untreated cells. Specific genes
      were selected for consideration. Real-time PCR confirmed results obtained from
      analysis of the microarray data for the genes phenol sulphotransferase (PST),
      intercellular adhesion molecule-1 (ICAM-1), transforming growth factor beta-3
      (TGF beta-3) and calreticulin. These studies were designed to provide base-line
      data on the gene expression-altering capacity of a specific chemical at a low
      dose, and will allow assessment of the possible deleterious effects that may be
      caused in human cells by exposure to the agricultural chemical Enable.

PMID- 15942998
TI  - Secondary prevention of schizophrenia: utility of standardized scholastic tests
      in early identification.
AB  - BACKGROUND: Given the enormous societal burden of schizophrenia, there has been a
      growing interest in its prevention during the past decade. Early detection and
      prompt treatment may improve outcome in schizophrenia. In this study, we examine
      the value of using pre-morbid cognitive impairment in early detection. METHODS:
      Standardized achievement tests Iowa Test of Basic Skills (ITBS) and Iowa Tests of
      Educational Development (ITED) at Grades 4, 8 and 11 were examined in 70 patients
      with schizophrenia and 147 comparison subjects without schizophrenia. The
      majority of comparison subjects later developed another major mental illness such
      as substance abuse or mood disorder. Receiver operating characteristic curves
      were used to test the efficiency and accuracy of pre-morbid cognitive tests for
      differentiating adolescents who will later develop schizophrenia from those who
      remain well or develop another mental illness. RESULTS: Although schizophrenia
      patients had lower mean percentile ranks than comparison subjects in every
      ITBS/ITED sub-test, these differences were only associated with small increases
      in risk for schizophrenia. Standardized scholastic tests achieved moderate
      sensitivity and specificity, and enhanced the detection of schizophrenia by three
      to five fold. However, positive predictive values were low. ITBS/ITED scores
      alone cannot be used in screening the general population, given the low positive
      predictive values. CONCLUSION: Combining ITBS/ITED scores with other risk
      factors, such as family history, may lead to more efficient early detection. Our
      findings illustrate the challenges facing the secondary prevention of
      schizophrenia. Priority should be given to developing efficient and accurate
      methods of early detection in order to reduce the dangers of making erroneous
      false positive diagnoses, and to decrease exposure to unnecessary treatment
      during the testing of early interventions.

PMID- 15942999
TI  - [Gap functions and diseases].
AB  - Gap junctions are highly conserved structures that provide cells with a direct
      pathway for sharing ions, nutrients and other intracellular messengers, thus
      participating to the homeostasis of various tissues. Research on transgenic mice
      has revealed a major involvement of gap junctions proteins (connexins) in several
      cellular functions. At the same time, an increasing number of mutations of
      connexin genes has been linked to several hereditary diseases, including
      peripheral neuropathies, skin diseases, genetic deafness, cataracts and some
      forms of epilepsy. This review summarizes the state of knowledge about the
      implication of connexins in human pathologies.

PMID- 15943000
TI  - [Gap junctions and secretion].
AB  - The emergence of multicellular organisms has necessitated the development of
      mechanisms for interactions between adjacent and distant cells. A consistent
      feature of this network is the expression of gap junction channels between the
      secretory cells of all glands so far investigated in vertebrates. Here, we
      reviewed the distribution of the gap junctions proteins, named connexins, in a
      few mammalian glands, and discussed the recent evidence pointing to the
      participation of these proteins in the functioning of endocrine and exocrine
      cells. Specifically, available data indicate the importance of gap junctions for
      the proper control of glucose-induced insulin secretion. Understanding the
      functions of beta-cell connexins are crucial for the engineering of surrogate
      cells, which is necessary for implementation of a replacement cell therapy in
      diabetic patients.

PMID- 15943001
TI  - Guidelines for vaginal birth after previous Caesarean birth.
AB  - OBJECTIVE: To provide evidence-based guidelines for the provision of a trial of
      labour (TOL) after Caesarean section. OUTCOME: Fetal and maternal morbidity and
      mortality associated with vaginal birth after Caesarean (VBAC) and repeat
      Caesarean section. EVIDENCE: MEDLINE database was searched for articles published
      from January 1, 1995, to February 28, 2004, using the key words "vaginal birth
      after Caesarean (Cesarean) section". The quality of evidence is described using
      the Evaluation of Evidence criteria outlined in the Report of the Canadian Task
      Force on the Periodic Health Exam. RECOMMENDATIONS: 1. Provided there are no
      contraindications, a woman with 1 previous transverse low-segment Caesarean
      section should be offered a trial of labour (TOL) with appropriate discussion of
      perinatal risks and benefits. The process of informed consent with appropriate
      documentation should be an important part of the birth plan in a woman with a
      previous Caesarean section (II-2B). 2. The intention of a woman undergoing a TOL
      after Caesarean section should be clearly stated, and documentation of the
      previous uterine scar should be clearly marked on the prenatal record (II-2B). 3.
      For a safe labour after Caesarean section, a woman should deliver in a hospital
      where a timely Caesarean section is possible. The woman and her health care
      provider must be aware of the hospital resources and the availability of
      obstetric, anesthetic, pediatric, and operating-room staff (II-2A). 4. Each
      hospital should have a written policy in place regarding the notification and
      (or) consultation for the physicians responsible for a possible timely Caesarean
      section (III-B). 5. In the case of a TOL after Caesarean, an approximate time
      frame of 30 minutes should be considered adequate in the set-up of an urgent
      laparotomy (III-C). 6. Continuous electronic monitoring of women attempting a TOL
      after Caesarean section is recommended (II-2A). 7. Suspected uterine rupture
      requires urgent attention and expedited laparotomy to attempt to decrease
      maternal and perinatal morbidity and mortality (II-2A). 8. Oxytocin augmentation
      is not contraindicated in women undergoing a TOL after Caesarean section (11-2A).
      9. Medical induction of labour with oxytocin may be associated with an increased
      risk of uterine rupture and should be used carefully after appropriate
      counselling (II-2B). 10. Medical induction of labour with prostaglandin E2
      (dinoprostone) is associated with an increased risk of uterine rupture and should
      not be used except in rare circumstances and after appropriate counselling (II
      2B). 11. Prostaglandin E1 (misoprostol) is associated with a high risk of uterine
      rupture and should not be used as part of a TOL after Caesarean section (II-2A).
      12. A foley catheter may be safely used to ripen the cervix in a woman planning a
      TOL after Caesarean section (II-2A). 13. The available data suggest that a trial
      of labour in women with more than 1 previous Caesarean section is likely to be
      successful but is associated with a higher risk of uterine rupture (II-2B). 14.
      Multiple gestation is not a contraindication to TOL after Caesarean section (II
      2B). 15. Diabetes mellitus is not a contraindication to TOL after Caesarean
      section (II-2B). 16. Suspected fetal macrosomia is not a contraindication to TOL
      after Caesarean section (II-2B). 17. Women delivering within 18 to 24 months of a
      Caesarean section should be counselled about an increased risk of uterine rupture
      in labour (II-2B). 18. Postdatism is not a contraindication to TOL after
      Caesarean section (II-2B). 19. Every effort should be made to obtain the previous
      Caesarean section operative report to determine the type of uterine incision
      used. In situations where the scar is unknown, information concerning the
      circumstances of the delivery is helpful in determining the likelihood of a low
      transverse incision. If the likelihood of a low transverse incision is high, a
      TOL after Caesarean section can be offered (II-2B). VALIDATION: These guidelines
      were approved by the Clinical Practice Obstetrics and Executive Committees of the
      Society of Obstetricians and Gynaecologists of Canada.

PMID- 15943002
TI  - Overexpression of c-myc and loss of heterozygosity on 2p, 3p, 5q, 17p and 18q in
      sporadic colorectal carcinoma.
AB  - AIM: The aim of the present study is to evaluate the prognostic influence of loss
      of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on
      surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor
      tissue samples from 153 patients were analyzed. Fifty-one percent of patients
      were male, and mean age in the series was 67 years. Tumors were located in the
      proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79
      patients. c-myc overexpression was studied by means of Northern blot analysis,
      and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc
      overexpression was detected in 25% of cases, and loss of heterozygosity in at
      least one of the studied regions in 48%. There was no association between
      clinical and pathologic features, and genetic alterations. The disease-free
      interval was significantly shorter for patients with both genetic alterations;
      the presence of both events was an independent prognostic factor for poor outcome
      in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of
      both loss of heterozygosity and overexpression of the c-myc oncogene separates a
      subset of colorectal carcinoma patients who have a shorter disease-free interval
      after curative-intent surgery.

PMID- 15943003
TI  - Umbilical cord blood banking: implications for perinatal care providers.
AB  - OBJECTIVE: To evaluate the risks and benefits of umbilical cord blood banking for
      future stem cell transplantation and to provide guidelines for Canadian perinatal
      care providers regarding the counselling, procedural, and ethical implications of
      this potential therapeutic option. OPTIONS: Selective or routine collection and
      storage of umbilical cord blood for future autologous (self) or allogenic
      (related or unrelated) transplantation of hematopoietic stem cells to treat
      malignant and nonmalignant disorders in children and adults. OUTCOMES: Maternal
      and perinatal morbidity, indications for umbilical cord blood transplantation,
      short- and long-term risks and benefits of umbilical cord blood transplantation,
      burden of umbilical cord blood collection on perinatal care providers, parental
      satisfaction, and health care costs. EVIDENCE: MEDLINE and PubMed searches were
      conducted from January 1970 to October 2003 for English-language articles related
      to umbilical cord blood collection, banking, and transplantation; the Cochrane
      library was searched; and committee opinions of the Royal College of
      Obstetricians and Gynaecologists, the American Academy of Pediatrics, and the
      American College of Obstetricians and Gynecologists were obtained. VALUES: The
      evidence collected was reviewed and evaluated by the Maternal/Fetal Medicine
      Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC),
      and recommendations were made using the evaluation of evidence guidelines
      developed by the Canadian Task Force on the Periodic Health Exam. BENEFITS,
      HARMS, AND COSTS: Umbilical cord blood is a readily available source of
      hematopoietic stem cells used with increasing frequency as an alternative to bone
      marrow or peripheral stem cells for transplantation in the treatment of malignant
      and nonmalignant conditions in children and adults. Umbilical cord blood
      transplantation provides a rich source of hematopoietic stem cells with several
      advantages, including prompt availability, decreased risk of transmissible viral
      infections and graft-versus-host disease (GVHD) in both human leukocyte
      antigen(HLA)-matched and HLA-mismatched stem cell transplants, and ease of
      collection with little risk to the mother or newborn. Potential limitations of
      umbilical cord blood transplantation include insufficient stem cell dose to
      reliably treat larger children and adult recipients, slower rate of engraftment,
      and the potential for transfer of genetically abnormal hematopoietic stem cells.
      The optimum method of umbilical cord blood transplantation is not yet clear,
      though available evidence would favour collection before delivery of the
      placenta. There are many unresolved ethical issues related to umbilical cord
      blood banking, particularly related to the rapid growth of private, for-profit,
      cord blood banks offering long-term storage for potential future autologous or
      related allogenic transplantation. The financial burden to the health care system
      for public cord blood banking and to families for private cord blood collection
      and storage is considerable. RECOMMENDATIONS: 1. Perinatal care providers should
      be informed about the promising clinical potential of hematopoietic stem cells in
      umbilical cord blood and about current indications for its collection, storage,
      and use, based on sound scientific evidence (II-3B). 2. Umbilical cord blood
      collection should be considered for a sibling or parent in need of stem cell
      transplantation when an HLA-identical bone marrow cell or peripheral stem cell
      donation from a sibling or parent is unavailable for transplantation (II-2B). 3.
      Umbilical cord blood should be considered when allogeneic transplantation is the
      treatment of choice for a child who does not have an HLA-identical sibling or a
      well-matched, unrelated adult bone marrow donor (II-2B). 4. Umbilical cord blood
      should be considered for allogeneic transplantation in adolescents and young
      adults with hematologic malignancies who have no suitable bone marrow donor and
      who require urgent transplantation (II-3B). 5. Altruistic donation of cord blood
      for public banking and subsequent allogeneic transplantation should be encouraged
      when umbilical cord blood banking is being considered by childbearing women,
      prenatal care providers, and(or) obstetric facilities (II-2B). 6. Collection and
      long-term storage of umbilical cord blood for autologous donation is not
      recommended because of the limited indications and lack of scientific evidence to
      support the practice (III-D). 7. Birth unit staff should receive training in
      standardized cord blood unit volume and reduce the rejection rate owing to
      labelling problems, bacterial contamination, and clotting (II-3B). 8. The safe
      management of obstetric delivery should never be compromised to facilitate cord
      blood collection. Manoeuvres to optimize cord blood unit volume, such as early
      clamping of the umbilical cord, may be employed at the discretion of the
      perinatal care team, provided the safety of the mother and newborn remains the
      major priority (III-A). 9. Collection of cord blood should be performed after the
      delivery of the infant but before delivery of the placenta, using a closed
      collection system and procedures that minimize risk of bacterial and maternal
      fluid contamination (see Figures 1a-1c) (I-B). 10. Public and private cord blood
      banks should strictly adhere to standardized policies and procedures for
      transportation, safety testing, HLA typing, cryopreservation, and long-term
      storage of umbilical cord blood units to prevent harm to the recipient, to
      eliminate the risk of transmitting communicable diseases, and thus to maximize
      the effectiveness of umbilical cord blood stem cell transplantation (II-1A). 11.
      Canada should establish registration, regulation, and accreditation of cord blood
      collection centres and banks (III-B). 12. Recruitment of cord blood donors should
      be fair and noncoercive. Criteria to ensure an equitable recruitment process
      include the following: (a) adequate supply to meet population transplantation
      needs; (b) fair distribution of the burdens and benefits of cord blood
      collection; (c) optimal timing of recruitment; (d) appropriately trained
      personnel; and (e) accurate recruitment message (III-A). 13. Informed consent for
      umbilical cord blood collection and banking should be obtained during prenatal
      care, before the onset of labour, with confirmation of consent after delivery
      (III-B). 14. Linkage of cord blood units and donors is recommended for public
      safety. Policies regarding the disclosure of abnormal test results to donor
      parents should be developed. Donor privacy and confidentiality of test results
      must be respected (III-C). 15. Commercial cord blood banks should be carefully
      regulated to ensure that promotion and pricing practices are fair, financial
      relationships are transparent, banked cord blood is stored and used according to
      approved standards, and parents and care providers understand the differences
      between autologous versus allogenic donations and private versus public banks
      (III-B). 16. Policies and procedures need to be developed by perinatal facilities
      and national health authorities to respond to prenatal requests for public and
      private cord blood banking (III-C).

PMID- 15943004
TI  - Mechanisms underlying the halotolerant way of Debaryomyces hansenii.
AB  - The yeast Debaryomyces hansenii is usually found in salty environments such as
      the sea and salted food. It is capable of accumulating sodium without being
      intoxicated even when potassium is present at low concentration in the
      environment. In addition, sodium improves growth and protects D. hansenii in the
      presence of additional stress factors such as high temperature and extreme pH. An
      array of advantageous factors, as compared with Saccharomyces cerevisiae, is
      putatively involved in the increased halotolerance of D. hansenii: glycerol, the
      main compatible solute, is kept inside the cell by an active glycerol-Na+
      symporter; potassium uptake is not inhibited by sodium; sodium protein targets in
      D. hansenii seem to be more resistant. The whole genome of D. hansenii has been
      sequenced and is now available at http://cbi.labri.fr/Genolevures/ and, so far,
      no genes specifically responsible for the halotolerant behaviour of D. hansenii
      have been found.

PMID- 15943005
TI  - Emergency department utilization during outbreaks of influenza.

PMID- 15943006
TI  - Specialty hospitals.

PMID- 15943007
TI  - Brain imaging research on subjective responses to psychotropic drugs.
AB  - OBJECTIVE: Neuroimaging studies on subjective responses to psychotropic drugs in
      humans were reviewed to examine progress in the field and identify gaps in
      knowledge. METHOD: An exhaustive search of computerized databases identified two
      categories of in vivo imaging studies: i) correlates of negative(dysphoric)
      subjective responses to neuroleptic use in schizophrenia, and ii) research on
      positive (euphoric) subjective responses, mostly from substance abuse population.
      RESULTS: Research has been largely confined to neurochemical imaging of dopamine
      in the striatal complex, confirming earlier speculations that impaired or
      deficient dopaminergic function is associated with dysphoric responses, and
      enhanced activity is associated with euphoric or pleasurable responses. Cerebral
      blood flow, regional metabolic rate and glucose utilization studies provided
      preliminary clues to the putative neuroanatomical sites. CONCLUSION: Neuroimaging
      techniques added credibility to the study of subjective responses; however,
      further studies are required to identify the underlying anatomical and
      neurochemical interactions in order to enhance their applied value.

PMID- 15943008
TI  - Subjective well-being under the neuroleptic treatment and its relevance for
      compliance.
AB  - OBJECTIVE: To review the concept of 'subjective well-being under neuroleptic
      treatment', its development and clinical relevance,particularly regarding
      compliance. METHOD: The manuscript includes a review of the limited literature
      and recent open and controlled clinical trials. RESULTS: The patients'
      perspective of antipsychotic treatment was largely neglected for a long time.
      Scientific interest in this field of strong clinical relevance started mainly
      with the development of atypical antipsychotics. Recent research indicates that
      subjective well-being (SW) is a major determinant of medication compliance in
      schizophrenia. There are several self-report instruments with sufficient internal
      consistency and good construct validity. Effects of antipsychotic treatment on
      psychopathology and SW are only partly related. Most patients strongly prefer the
      atypical over typical antipsychotics. The assessment of SW is helpful for
      selecting the optimal drug for the individual patient. CONCLUSION: SW, under
      antipsychotic treatment, is a valid construct; its assessment provides an
      independent outcome variable, which is relevant to compliance.

PMID- 15943009
TI  - Hydrophobic interaction chromatography: harnessing multivalent protein-surface
      interactions for purification procedures.
AB  - Hydrophobic interaction chromatography (HIC) is one of the basic purification
      procedures in the biosciences. However, because of its complexity, it has not
      gained the same foothold in the methodological repertoire of protein chemistry as
      has affinity chromatography or ion exchange chromatography. This is mainly a
      result of the lack of a general optimization procedure for the reversible
      adsorption and elution of a novel protein to be purified. Further problems arise
      from the fact that most commercial hydrophobic adsorbents are inadequate for an
      ideal performance in downstream processing procedures, because these media are
      too hydrophobic and elution of proteins in their native state is often
      impossible. Therefore, as in the 1970s, a bioscientist of today has to be capable
      of synthesizing a small library of hydrophobic gels from which he or she can then
      select and optimize the ideal matrix for their special needs. In addition, a
      general optimization method employing the critical hydrophobicity concept has now
      been devised that should allow the application of HIC methodology to many
      hitherto unpurified proteins. In this chapter, the reader is first introduced to
      the theoretical background (multivalence, negative cooperativity, adsorption
      hysteresis) of the binding of protein ligands to hydrophobic supports, so that
      they will be capable of independently adapting HIC to a novel protein. Then a
      simple nontoxic method is described for the synthesis of HIC-gel libraries
      consisting of a homologous series of uncharged alkyl-Sepharoses of three chain
      lengths (butyl, pentyl, and hexyl Sepharose) prepared with different degrees of
      separation. From this series a critical hydrophobicity gel can then be selected
      and employed for critical hydrophobicity HIC. A detailed example for the
      chromatography of human fibrinogen is given that has been employed as a one-step
      procedure for the purification of fibrinogen from human plasma.

PMID- 15943010
TI  - Performance of functions; claims for compensation under the Energy Employees
      Occupational Illness Compensation Program Act. Interim final rule; request for
      comments.
AB  - This document contains the interim final regulations governing the administration
      of the Energy Employees Occupational Illness Compensation Program Act of 2000, as
      amended (EEOICPA or Act) by the Department of Labor (Department or DOL). Part B
      of the Act provides uniform lump-sum payments and medical benefits to covered
      employees and, where applicable, to survivors of such employees, of the
      Department of Energy (DOE), its predecessor agencies and certain of its vendors,
      contractors and subcontractors. Part B of the Act also provides smaller uniform
      lump-sum payments and medical benefits to individuals found eligible by the
      Department of Justice (DOJ) for benefits under section 5 of the Radiation
      Exposure Compensation Act (RECA) and, where applicable, to their survivors. Part
      E of the Act provides variable lump-sum payments (based on a worker's permanent
      impairment and/or years of established wage-loss) and medical benefits for
      covered DOE contractor employees and, where applicable, provides variable lump
      sum payments to survivors of such employees (based on a worker's death due to a
      covered illness and any years of established wage-loss). Part E of the Act also
      provides these same payments and benefits to uranium miners, millers and ore
      transporters covered by section 5 of the RECA and, where applicable, to survivors
      of such employees. The Office of Workers' Compensation Programs (OWCP)
      administers the adjudication of claims and the payment of benefits under EEOICPA,
      with the Department of Health and Human Services (HHS) estimating the amounts of
      radiation received by employees alleged to have sustained cancer as a result of
      such exposure and establishing guidelines to be followed by OWCP in determining
      whether such cancers are at least as likely as not related to employment. Both
      DOE and DOJ are responsible for notifying potential claimants and for submitting
      evidence necessary for OWCP's adjudication of claims under EEOICPA.

PMID- 15943011
TI  - Intracoronary aminophylline for heart block with AngioJet thrombectomy.

PMID- 15943012
TI  - Force probe molecular dynamics simulations.
AB  - Many proteins are molecular nano-machines, which perform their biological
      function via well-coordinated structural transitions. Often, these motions occur
      on much slower time scales than those accessible to conventional molecular
      dynamics techniques, which are limited to submicrosecond time scales by current
      computer technology. This is also true for ligand binding and unbinding
      reactions. Force probe simulations (or steered molecular dynamics) provide a
      powerful means to overcome this limitation, and thus to get insight into the
      atomistic mechanisms that underlie biological functions such as ligand binding.
      This chapter provides a basic introduction into this method. It further sketches
      a simple nonequilibrium statistical mechanics treatment that shows how to relate
      the results of force probe simulations to atomic force microscopy (AFM) or
      optical tweezer experiments. As an example, enforced unbinding simulations of
      streptavidin/biotin complexes are detailed.

PMID- 15943013
TI  - Prescription drug benefits under Part D of the Medicare Modernization Act--the
      genie's out of the bottle.
AB  - With the passage of the Medicare Prescription Drug, Improvement and Modernization
      Act of 2003 came the creation of the Medicare Part D prescription drug benefit,
      which takes effect in January 2006. In this brief, we discuss the new Part D
      benefit, including who is eligible, the basic benefit, benefits for low-income
      individuals and coordination with other prescription drug coverage.

PMID- 15943014
TI  - [A new method of anaesthesia in laparoscopic cholecystectomy].

PMID- 15943015
TI  - [Laparoscopic transgastric removal of a benign tumor of the stomach].

PMID- 15943016
TI  - [Acute obturation biliary intestinal obstruction].

PMID- 15943017
TI  - [A foreign body of the appendix as a result of a suicidal attempt].

PMID- 15943018
TI  - Seeing through the 'MIST' (minor impact soft tissue injury)?

PMID- 15943019
TI  - Sleeping with the enemy? Where to draw the line on research funding?

PMID- 15943020
TI  - Narrative ARTifice and women's agency.
AB  - The choice to pursue fertility treatments is a complex one. In this paper I
      explore the issues of choice, agency, and gender as they relate to assisted
      reproductive technologies (ARTs). I argue that narrative approaches to bioethics
      such as those by Arthur Frank and Hilde Lindemann Nelson clarify judgments about
      autonomy and fertility medicine. More specifically, I propose two broad narrative
      categories that help capture the experience of encounters with fertility
      medicine: narratives of hope and narratives of resistance. This narrative
      typology captures the inevitable conflict that women feel when they become
      subjects of fertility medicine. On the one hand, they must remain hopeful; on the
      other, they must not surrender themselves completely. Nelson's account of
      counterstories as narratives of resistance helps us see how women can reconcile
      the experience of a strong desire to have children with the desire to remain
      authentic and whole.

PMID- 15943021
TI  - Research participation and the right to withdraw.
AB  - Most ethics committees which review research protocols insist that potential
      research participants reserve unconditional or absolute 'right' of withdrawal at
      any time and without giving any reason. In this paper, I examine what consent
      means for research participation and a sense of commitment in relation to this
      right to withdraw. I suggest that, once consent has been given (and here I am
      excluding incompetent minors and adults), participants should not necessarily
      have unconditional or absolute rights to withdraw. This does not imply that there
      should be a complete absence of rights, or, indeed, an abandonment of the right
      to withdraw. The point of this paper is to show that the supposed unconditional
      or absolute nature of these rights may be self-defeating and so fail to respect
      the autonomy of participants. In addition, and on a more positive note, I suggest
      that, attaching certain conditions on the right to withdraw, may better respect
      the autonomy of these participants by underlining the idea that autonomy is more
      than mere whim or indifference to the fate of others. On the contrary, research
      staff are currently unable to 'push' participants, who may merely have logistical
      difficulties unrelated to the research itself, but who really want to stay the
      course, for fear of coercing them. Furthermore, researchers now try to 'screen
      out' people they think may be unreliable to protect the science of the study and
      so groups at risk of dropping out may be unfairly denied access to research
      treatments. I conclude that on-going negotiation between the relevant parties
      could be on balance the only truly acceptable way forward but concede certain
      important limitations to take into account.

PMID- 15943022
TI  - Does a normal foetus really have a future of value? A reply to Marquis.
AB  - The traditional approach to the abortion debate revolves around numerous issues,
      such as whether the foetus is a person, whether the foetus has rights, and more.
      Don Marquis suggests that this traditional approach leads to a standoff and that
      the abortion debate 'requires a different strategy.' Hence his 'future of value'
      strategy, which is summarized as follows: (1) A normal foetus has a future of
      value. (2) Depriving a normal foetus of a future of value imposes a misfortune on
      it. (3) Imposing a misfortune on a normal foetus is prima facie wrong. (4)
      Therefore, depriving a normal foetus of a future of value is prima facie wrong.
      (5) Killing a normal foetus deprives it of a future value. (6) Therefore, killing
      a normal foetus is prima facie wrong. In this paper, I argue that Marquis's
      strategy is not different since it involves the concept of person--a concept
      deeply rooted in the traditional approach. Specifically, I argue that futures are
      valuable insofar as they are not only dominated by goods of consciousness, but
      are experienced by psychologically continuous persons. Moreover, I argue that his
      strategy is not sound since premise (1) is false. Specifically, I argue that a
      normal foetus, at least during the first trimester, is not a person. Thus, during
      that stage of development it is not capable of experiencing its future as a
      psychologically continuous person and, hence, it does not have a future of value.

PMID- 15943023
TI  - Ethics and synthetic gametes.
AB  - The recent in vitro derivation of gamete-like cells from mouse embryonic stem
      (mES) cells is a major breakthrough and lays down several challenges, both for
      the further scientific investigation and for the bioethical and biolegal
      discourse. We refer here to these cells as gamete-like (sperm-like or oocyte
      like, respectively), because at present there is still no evidence that these
      cells behave fully like bona fide sperm or oocytes, lacking the fundamental
      proof, i.e. combination with a normally derived gamete of the opposite sex to
      yield a normal individual. However, the results published so far do show that
      these cells share some defining features of gametes. We discuss these results in
      the light of the bioethical and legal questions that are likely to arise would
      the same process become possible with human embryonic stem (hES) cells.

PMID- 15943024
TI  - Development of engineered stationary phases for the separation of carotenoid
      isomers.
AB  - A variety of bonded phase parameters (endcapping, phase chemistry, ligand length,
      and substrate parameters) were studied for their effect on column retention and
      selectivity toward carotenoids. Decisions were made on how each of these
      variables should be optimized based on the separation of carotenoid and
      polycyclic aromatic hydrocarbon test probes. A column was designed with the
      following properties: high absolute retention, enhanced shape recognition of
      structured solutes, and moderate silanol activity. These qualities were achieved
      by triacontyl (C30) polymeric surface modification of a moderate pore size
      (approximately 20 nm), moderate surface area (approximately 200 m2/g) silica,
      without subsequent endcapping. The effectiveness of this "carotenoid phase" was
      demonstrated for the separation of a mixture of structurally similar carotenoid
      standards, an extract of a food matrix Standard Reference Material, and a beta
      carotene dietary supplement under consideration as an agent for cancer
      intervention/prevention.

PMID- 15943025
TI  - Dental postcards no. XXVIII.

PMID- 15943026
TI  - Haemopoietic growth factors in myelodysplastic syndromes: towards patient
      oriented therapy?
AB  - Recombinant human erythropoietin (r-EPO) has been used in Myelodysplastic
      Syndrome (MDS) patients with anaemia since the early nineties. In low-risk MDS
      patients, other haemopoietic growth factors (HGFs) (granulocyte-colony
      stimulating factor, G-CSF, granulocyte-macrophage-colony stimulating factor, GM
      CSF, and interleukin 3, IL-3) have been used to synergise the effects of r-EPO on
      erythroid growth and to increase neutrophil count in patients with severe
      neutropenia. In high-risk MDS, or in patients with post-MDS AML, myeloid HGFs
      have been used to push blasts into the S-phase, thus increasing their sensitivity
      to antiblastic drugs. Several trials have shown that r-EPO can increase
      haemoglobin levels and improve QoL in patients with anaemia associated to MDS.
      The selection of patients with a high probability of response to HGFs is based on
      the careful consideration of several clinical and biological parameters, i.e.,
      among others, basal EPO and transfusional needs, disease duration, FAB or WHO
      subtypes, and IPSS score. Treatment of anaemic MDS patients with HGFs should
      become "patient oriented" and different types, schedules, and duration of
      treatment have to be designed according to the specific criteria which most
      likely predict, for each individual patient, the best chance of responding
      favourably to therapy.

PMID- 15943027
TI  - Supportive therapy in neuro-oncology.
AB  - Patients with cerebral neoplasms often report pain or other kinds of symptoms
      which, even though not directly connected to the disease itself, can cause
      complications in the approach to therapy and worsen the quality of life of the
      patients. The therapies aimed at controlling these kinds of disturbances are
      referred to as supportive therapies as they do not cure the underlying disease.
      However, these therapies should not be underestimated, because, by controlling
      these disturbances, they are able not only to greatly improve the quality of life
      of the neuro-oncologic patients but also increase their survival. Based on this
      hypothesis, we will discuss and examine the drugs more frequently used for
      supportive therapy in neuro-oncologic patients. We assert, in fact, that the
      desire to offer neuro-oncologic patients better assistance guarantees not only
      adequate specialized input from the health operators involved, concerning the
      quality of life and the uniqueness of the 'person-patient', but also the ability
      to be able to listen to the patients, understand their choices and allow them to
      express their priorities.

PMID- 15943028
TI  - Apoptosis and human placenta: expression of proteins belonging to different
      apoptotic pathways during pregnancy.
AB  - Apoptosis occurs during normal development and it is important for the right
      balance between the loss of old, non-functional cells and the formation of new
      cells in different organs and tissues. Apoptosis is triggered by different cell
      type-specific signals which involve several pathways, such as mitochondrial and
      receptor-mediated pathways, resulting in caspase cascade activation. Several
      studies have suggested that apoptosis plays an important role in the normal
      development, remodelling and aging of the placenta. Moreover, it has been
      demonstrated that apoptosis increases as pregnancy progresses suggesting that it
      is a normal physiological phenomenon throughout gestation. In the last years, it
      has been hypothesized that the process known as syncytial fusion is directly or
      indirectly related to apoptotic events. In particular, it has been suggested that
      cytotrophoblast cells early express most important apoptotic proteins that
      translocate in the syncytiotrophoblast with the fusion. This suggests that
      apoptosis has a central role in the villous trophoblast turnover. Recently,
      another important involvement of apoptotic processes in human placenta has been
      demonstrated. In particular, the apoptosis, mainly through Fas-FasL or TRAIL-R
      TRAIL signalling, may be a defence mechanism against rejection of the fetal
      allograft by maternal immune system. The whole data suggest that regulation of
      apoptotic events is important to allow a correct development, differentiation and
      function of the placenta throughout pregnancy and that an unbalance of this
      process leads to severe pathologies such as pre-eclampsia and intrauterine growth
      retardation. Therefore, due to its extensive proliferation and invasive
      properties, the placenta mimics a malignant tumor and represents an interesting
      model to evaluate those processes leading to carcinogenesis.

PMID- 15943029
TI  - Optimal procedure for thermal delivery in hyperthermic/chemotherapeutic
      treatments in the isolated perfusion of the the limbs.
AB  - Isolated locoregional limbs perfusion treatments of various malignancies have
      demonstrated synergistic efficacy when hyperthermia was associated with
      chemotherapy. This paper delineates the criteria, the technical provisions and
      the specifications that have been improved and implemented at our Institution. It
      is believed that, following the indications offered in this paper, several,
      apparently still unsolved problems of treatment planning and implementation will
      be overcome, offering closely controlled and highly reproducible procedures with
      a significant progress in the feasibility of reliable comparisons of the results
      among different research centres and in the reduction of the occurrence of
      controversial results or unexpected complications.

PMID- 15943030
TI  - Low dose-intensity docetaxel in the treatment of pre-treated elderly patients
      with metastatic breast cancer.
AB  - We evaluated the efficacy and toxicity profile of single-agent docetaxel
      administered in daily clinical practice at low-dose regimen in 37 pre-treated
      elderly patients with metastatic breast cancer previously exposed to
      chemotherapy. Docetaxel was employed by physician's preference according to a
      weekly (8 patients, 25-30 mg/m2 every 7 days), bi-weekly (19 patients, 40-50
      mg/m2 every 14 days), or tri-weekly (10 patients, 75-100 mg/m2 every 21-28 days)
      schedule. The median age of patients was 70 yrs, and most of them (84%) had a
      good PS; visceral metastases were found in 26 patients. Twenty-five patients were
      pre-treated by two or more chemotherapy lines. Anthracycline or
      anthracycline/paclitaxel therapy was previously employed in 25 patients (67%).
      Median delivered dose-intensity of docetaxel was 21 mg/m2/week (range 11-32),
      without significant differences between the regimens used. Thirty-three patients
      were evaluable for response. Eight (24%) patients had objective responses (2
      complete and 6 partial) to docetaxel, with a median duration of response of 18
      months; 14 (42%) patients had stable disease lasting more than 6 months (median
      10 months). Median overall time to progression was 6 months. Median overall
      survival was 16 months, with 1- and 2-year survival rates of 64% and 34%,
      respectively. Grade 3/4 toxicities were rare: leucopenia in 18% of patients,
      neutropenia in 13%, emesis in 8%, diarrhea in 5%, and mucositis in 5%. Severe
      fatigue was recorded in 4 patients. In conclusion, docetaxel, even when
      administered at low dose-intensity, demonstrated good disease control and
      toxicity profile. This approach provides an excellent alternative for pre-treated
      elderly patients with advanced breast cancer.

PMID- 15943031
TI  - Epstein-Barr virus-associated gastric carcinoma in Lima, Peru.
AB  - We examined 254 gastric carcinomas (GCs) diagnosed in four hospitals in Lima,
      Peru, and its suburban area during the period between 1994-2001. Epstein-Barr
      virus (EBV)-associated gastric carcinoma (EBVaGC) was identified by the in situ
      hybridization (ISH) technique to detect EBV-encoded small RNA (EBER) in gastric
      tissue. EBVaGCs, where EBER ISH staining was observed in all carcinoma cells,
      accounted for 3.9% (10/254) of gastric adenocarcinomas, the lowest frequency ever
      reported in Latin American countries. EBVaGC incidence rates in Peru, which we
      estimated on the basis of the present study and cancer incidence in Lima, were
      0.8 per 100,000 among men and 0.5 per 100,000 among women. These estimates are
      much lower than those reported in our previous studies in Colombia (4.1 and 1.4
      per 100,000 among men and women, respectively), a neighboring country, and in
      Japan (6.4 and 1.1 per 100,000 among men among women, respectively).
      Interestingly, EBVaGC in Peru showed no evident male predominance, as opposed to
      the findings reported in a majority of studies. Other clinicopathological
      features of EBVaGC in Peru were similar to those found in literature: EBVaGC
      showed no age dependence, a predominance in the non-antrum part of the stomach,
      and high frequencies in histological subtypes of moderately differentiated
      tubular adenocarcinoma and solid poorly differentiated adenocarcinoma. There was
      a case of well-differentiated adenocarcinoma showing a partial EBER-1-positive
      staining. In this carcinoma, the tumor in the body (middle third of the stomach)
      was EBER-1 positive but the tumor in the stomach antrum showed no noticeable EBER
      1 ISH staining. We suspect this was a case of synchronous double carcinomas.
      Further studies are needed to identify the cause of the low frequency and lack of
      male predominance of EBVaGC in Peru.

PMID- 15943032
TI  - Lovastatin enhances in vitro radiation-induced apoptosis of rat B-cell lymphoma
      cells.
AB  - Our previous demonstration of an antimetastatic effect of lovastatin, both in rat
      sarcoma and lymphoma tumor-models, as well as the fact that lovastatin and
      radiation are able to stop the cell cycle in different phases, suggested the
      feasibility of a combined treatment. We studied the effect of the in vitro
      combined treatment of a B-cell rat lymphoma (L-TACB) with lovastatin and
      irradiation. The results herein obtained provide new information about the role
      of statins as radiosensitizers. The antitumor effect of the combined treatment
      was higher than that elicited by either treatment alone. This effect could be a
      consequence, at least in part, of an enhanced apoptosis.

PMID- 15943033
TI  - The evaluation of cytotoxic activity of planar pentadentate ligand 2',2"'-(2,6
      pyridindiyldiethylidyne) dioxamohydrazide dihydrate (H2l x 2H2O) and its metal
      coordination complexes; pitfalls in the use of the MTT-assay.
AB  - In this study we have investigated, for the first time to our knowledge, the
      antineoplastic activity of a planar pentadentate ligand (H2L.2H2O = 2', 2'''-(2,6
      pyridindiyldiethylidyne)dioxamohydrazide dihydrate) and some of its metal
      coordination complexes [Cu(L)(H2O)].H2O, [Cu(HL)(H2O)]Cl04, [Co(L)(H20)2] 6H20,
      [Co(H2L)(H2O)(MeOH)](ClO4)2 and [Fe(L)(H2O)2]ClO4-3H2O, as well as of inorganic
      salts CuCl2 2H20, CoCl2 6H2O and FeCl3.6H2O of corresponding metal ions. The
      antiproliferative activity of these compounds was examined in a human melanoma
      cell line FemX with exposure time of 48 hours by performing two cytotoxicity
      tests: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
      and sulforhodamine B (SRB) assay. Among these substances, the ligand H2L.2H2O
      expressed the greatest antineoplastic activity IC50 = 45.40 microM, while the
      IC50 of others could not be determined by SRB assay in the examined range of
      concentrations due to their low activity. FeCl3.6H2O showed stimulatory activity.
      We have found remarkable discrepancies between the results obtained by MTT assay
      and SRB assay that influence IC50 value as well as other measures of
      cytotoxicity, which led to the conlusion of uncertainty of using the MTT assay in
      evaluation of antineoplastic activity of organometalic complexes and inorganic
      metal salts.

PMID- 15943034
TI  - Interleukin-15 and transforming growth factor alpha are associated with depletion
      of tumor-associated macrophages in colon cancer.
AB  - We examined the effects of IL-15 and TGF-alpha on the inhibition of macrophage
      infiltration into colon cancer tissue, and secretion of amphoterin from colon
      cancer cells. Production of IL-15 and/or TGF-alpha was associated with depletion
      of tumor-associated macrophages (TAMs) in both Dukes' B and C tumors (P = 0.0324
      and 0.0051, respectively). Production of IL-15 and/or TGF-alpha was also
      associated with amphoterin mRNA expression in colon cancer tissues with TAM
      depletion in both Dukes' B and C tumors (P = 0.0167 and P = 0.0062,
      respectively). WiDr human colon cancer cells treated with IL-15 and/or TGF-alpha
      induced reduction of nucleus-localized amphoterin and an increase in cytosolic
      and membranous amphoterin. Moreover, IL-15 and/or TGF-alpha treatment increased
      amphoterin secretion by WiDr cells. Most notably, IL-15 and TGF-alpha treatment
      induced the increase of cytosol/membrane localization and secretion of amphoterin
      and the most pronounced effect among the treatments carried out. These results
      suggested that IL-15/TGF-alpha promotes depletion of TAMs and secretion of
      amphoterin in colon cancer.

PMID- 15943035
TI  - Expression of a CD44 variant and VEGF-C and the implications for lymphatic
      metastasis and long-term prognosis of human breast cancer.
AB  - The aim of the present study was to determine whether expression of the CD44
      variant v7-v8 (CD44v7-v8) or vascular endothelial growth factor-C (VEGF-C) is
      associated with long-term prognosis in breast cancer patients. A 10-year follow
      up of 91 patients with primary breast cancer who were previously assessed for
      CD44 expression was undertaken. Immunohistochemical evaluation of VEGF-C
      expression was performed in 87 of these patients and their long-term prognosis
      was assessed. The disease-free and overall survival rates were significantly
      poorer for the CD44v7-v8-positive patients than for the patients negative for
      this marker. VEGF-C expression was detected in 38 out of the 87 patients (43.7%)
      with primary human breast cancer. There were no significant differences in tumor
      size, histological type, axillary lymph node status, presence of lymphatic or
      venous invasion, or presence of estrogen receptors and progesterone receptors
      between the VEGF-C-positive and -negative patients. There were also no
      significant differences in the disease-free or overall survival rates in these
      patient groups. In conclusion after the 10-year follow-up, expression of CD44v7
      v8 was associated with poor prognosis for breast cancer patients. However, there
      was no association between VEGF-C expression and the clinicopathological factors
      or prognosis of breast cancer patients.

PMID- 15943036
TI  - Expression of beta-catenin, E-cadherin and cyclin D1 in adenoid cystic carcinoma
      of the salivary gland.
AB  - We evaluated the expression of beta-catenin, E-cadherin, and cyclin-D1 in 23
      cases of adenoid cystic carcinoma (ACC) of the salivary gland. We detected beta
      catenin on the cell membranes in all ACCs, but its distribution was irregular, as
      compared to that on normal structures. In three out of the 23 cases, beta-catenin
      was detected in the nuclei, as well as on cell membranes. Polymerase chain
      reaction (PCR) and direct sequencing revealed a missense mutation in one case in
      which beta-catenin had been detected in the nuclei of tumor cells. We also
      detected E-cadherin on cell membranes with a similar irregular distribution to
      that of beta-catenin. In 11 cases (almost 48%) of ACC, cyclin D1 was localized in
      cell nuclei but there was no correlation with the nuclear staining of the beta
      catenin. Our results suggest that disturbances in the distribution of beta
      catenin and E-cadherin might affect the morphology ofACC and that a small
      fraction of cases of ACC are characterized by a mutation in the beta-catenin
      gene, which is associated with the nuclear accumulation of the product of this
      gene but does not affect the transcription of the gene for cyclin-D1.

PMID- 15943037
TI  - Immunohistochemical detection of epidermal growth factor receptor in human high
      grade astrocytomas--a comparison between frozen- and paraffin sections.
AB  - The overexpression of epidermal growth factor receptor (EGFR) in human astrocytic
      tumours is associated with the oncogenesis of these tumours. Ongoing research on
      diagnostic, prognostic, and therapeutic aspects of this receptor is highly
      dependent on the development of reliable techniques for the detection of EGFR in
      tumour tissue. The aim of this study was to assess EGFR expression in human high
      grade astrocytomas by means of immunohistochemistry on formalin-fixed, paraffin
      embedded sections and to compare these findings with the results of our previous
      study on frozen sections from these tumours, in which we found about 60% EGFR
      positivity (10). Four anaplastic astrocytomas and 19 glioblastomas were included
      in this study. Two different antibodies were used, the monoclonal antibody E30
      reactive against the extracellular domain of EGFR and the polyclonal antibody Ab
      4 directed against its cytoplasmic domain. With E30, 3 out of 4 anaplastic
      astrocytomas (75%) and 12 out of 19 glioblastomas (63%) were found to express
      EGFR whereas Ab-4 demonstrated positive EGFR immunoreactivity in most of the
      tumours (18/19 glioblastomas and all the 4 anaplastic astrocytomas). In
      conclusion, immunohistochemistry represents a reliable and convenient technique
      for the detection of EGFR in tissue sections of human high-grade astrocytomas,
      and that EGFR immunoreactivity is comparable in frozen- and paraffin sections
      from these tumours.

PMID- 15943038
TI  - Combination of boron and gadolinium compounds for neutron capture therapy. An in
      vitro study.
AB  - In neutron capture therapy, the therapeutic effect of the boron compound is based
      on alpha particles produced by the B(n, alpha) reaction while with the gadolinium
      compound the main radiation effect is from gamma rays derived from the Gd(n,
      gamma) reaction. The uptake and distribution within the tumor may be different
      among these compounds. Thus, the combination of the boron and gadolinium
      compounds may be beneficial for enhancing the radiation dose to the tumor.
      Chinese hamster fibroblast V79 cells were used. For the neutron targeting
      compounds, 10B (BSH) at 0, 5, 10, and 15 ppm, and 157Gd (Gd-BOPTA) at 0, 800,
      1600, 2400, 3200, and 4800 ppm, were combined. The neutron irradiation was
      performed with thermal neutrons for 30 min. (neutron flux: 0.84 x 10(8) n/cm2/s
      in free air). The combination of the boron and gadolinium compounds showed an
      additive effect when the gadolinium concentration was lower than 1600 ppm. This
      additive effect decreased as a function of gadolinium concentration at 2400 ppm
      and resulted in no additive effect at more than 3200 ppm of gadolinium. In
      conclusion, the combination of the boron and gadolinium compounds can enhance the
      therapeutic effect with an optimum concentration ratio. When the gadolinium
      concentration is too high, it may weaken the boron neutron capture reaction due
      to the high cross-section of gadolinium compound against neutrons.

PMID- 15943039
TI  - Anorexia and cachexia in prostaglandin EP1 and EP3 subtype receptor knockout mice
      bearing a tumor with high intrinsic PGE2 production and prostaglandin related
      cachexia.
AB  - Previous studies in our laboratory have suggested that prostaglandin (PG) E2 is
      involved in anorexia/cachexia development in MCG 101 tumor-bearing mice. However,
      the role of COX pathways in the pathogenesis of cancer anorexia/cachexia is not
      fully resolved. In the present study, we investigated the role of PGE receptors
      subtype EP1 and EP3 on the development of anorexia in MCG 101-bearing mice. Our
      results show that the absence of host EP1 or EP3 receptors did not alter the
      magnitude of anorexia in tumor-bearers. However, anorexia in tumor-bearing EP1
      and EP3 knockouts was not improved by indomethacin treatment as observed in wild
      type tumor-bearers. By contrast, indomethacin improved body composition similar
      in EP1 and EP3 knockouts as well as in wild type tumor-bearing animals and tumor
      growth was retarded in EP1 and promoted in EP3 knock outs. Our results
      demonstrate that host EP1 and EP3 receptors are involved in the control of local
      tumor growth, which translates into anorexia, this being the main cause of
      metabolic adaptive alterations to explain weight loss in this model. Brain EP1
      and EP3 subtype receptors do not seem to directly control anorexia, which leaves
      EP2 and EP4 as potential candidates.

PMID- 15943040
TI  - Influence of time interval between surgery and radiotherapy on tumor regrowth.
AB  - In order to evaluate the influence of time intervals between tumor cell injection
      and radiotherapy on tumor control and regrowth after surgery, we performed two
      kinds of experiments on C3D2F1 mice bearing a mammary carcinoma inoculated in the
      foot or leg. 1st experiment: tumor in foot. END POINT: Tumor Control Probability
      (TCP). Single dose radiation treatments (RT) were administered at different
      period times from injection time of tumor cells (day 1). 1st group: unirradiated
      control, 2nd group: RT on day 2 (TCP50 29 +/- 2.1 Gy), 3rd group: RT on day 7
      (TCP 52.5 +/- 2.9 Gy), 4th group: RT on day 12 (TCP50 61.9 + 2.4 Gy). 2nd
      experiment: tumor in leg. END POINT: percentage of tumor regrowth. Mice were
      randomly assigned to three groups: 1st control group (tumor growth in all mice),
      2nd surgical excision of macroscopically evident tumor on day 7-9 from injection
      (tumor regrowth in 85% of mice), 3rd as the previous group plus 30 Gy radiation
      treatment within 24 hours from excision (tumor regrowth in 33% of cases). The
      radiation dose was selected on the basis of TCP50 observed in the 1st experiment
      for mice with sub-clinical disease. These data indicate that the radiation dose
      able to control 50% of tumors increases with the time interval between tumor
      cells injection and RT. A short time interval between surgery and RT should
      increase the probability of local control, supporting the rationale of
      intraoperative radiation therapy (IORT) as adjuvant therapy after surgical
      resection, when subclinical residual cells are suspected.

PMID- 15943041
TI  - A comparative study of P53/MDM2 genes alterations and P53/MDM2 proteins
      immunoreactivity in liver cirrhosis and hepatocellular carcinoma.
AB  - In the present study, the expression of P53 and MDM2 proteins were examined in
      specimens from a group of 20 patients (9 with primary hepatocellular carcinoma
      HCC and 11 with liver cirrhosis LC, linked to HBV infections as a major
      aetiologic factor) by immunohistochemistry. The immunostaining findings were
      correlated with P53 mutation analysis using PCR-SSCP, PCR-HDF and direct
      sequencing, and MDM2 amplification studies by differential PCR. P53
      immunopositivity was found in 9 out of the 20 (45.0%) cases. Mutations of the P53
      gene were detected in 5 (55%) tumors and 3 (27%) LC samples; 7 of these cases
      revealed P53 immunoreactivity. The mutations were base transitions at codons 175,
      245 and 273; no changes were observed at codon 249, characteristic for aflatoxins
      action. MDM2 immunopositivity was revealed in 9 out of 20 (45.0%) specimens. MDM2
      amplification occurred in 4 (44.4%) and 1 (9.1%) cases, HCC and LC specimens
      respectively; only in 2 tumors (10.0%), which exhibited MDM2 immunoreactivity.
      Overall, MDM2 positivity was not associated with MDM2 amplification in 7 out of
      the 20 studied samples (35.0%). Two HCC patients were found to have both gene
      abnormalities. Either the mutation rate of the P53 gene as well as the
      amplification level of the MDM2 gene was higher in HCC than in precancerous liver
      tissue stages. These results support the notion that besides P53 alterations,
      MDM2 gene deregulation seems to be an important event in hepatocarcinogenesis.
      Additionally, the mechanism of MDM2-mediated degradation of P53 protein, without
      involving stabilization and inactivation of P53 gene, should be considered for
      the understanding of all features of tumor progression processes.

PMID- 15943042
TI  - Dermatofibrosarcoma protuberans occuring in a child.
AB  - Dermatofibrosarcoma protuberans (DFSP) usually occurs in adults, however it can
      also occur in infancy and childhood. Diagnosis of DFSP in children is quite
      difficult given the rarity of the tumor and its variegated appearance. The
      behavior of this neoplasm is of borderline or intermediate malignancy with a high
      rate of recurrence but limited metastatic potential. We present the case of an
      eleven-year old boy who presented with a slightly raised, not tender lesion on
      his right shoulder. It had appeared two years before as a red-brown plaque and
      since then it had gradually grown to a nodule. An excisional biopsy was
      performed, and the diagnosis of DFSP was made based on the histological and
      immunohistochemical findings.

PMID- 15943043
TI  - Primary intimal sarcoma of the thoracic aorta.
AB  - Primary aortic tumors are well known for both their rarity and variability in
      clinical presentation and usually are diagnosized post-operatively or by post
      mortem examination. Intimal sarcoma is a recurrent histological variant and the
      involvement of the thoracic aorta is an unusual presentation. Angiography and
      computed tomography are accurate methods to evaluate aortic tumors though
      transesophageal echocardiography is actually used for the differential diagnosis.
      Here, we describe an unusual intimal sarcoma of the thoracic aorta whose clinical
      feature strongly mimicked a diffuse thrombotic disease.

PMID- 15943044
TI  - Squamous and adenosquamous cell carcinomas of the gallbladder.
AB  - Squamous and adenosquamous cell carcinomas (ASC and SCC) are rare subtypes of
      gallbladder cancer, traditionally considered more aggressive and with a poorer
      prognosis than adenocarcinoma. We report about two patients affected by an
      advanced squamous cell carcinoma of the gallbladder. Both had a large tumour in
      the gallbladder fossa region with infiltration of the liver. Surgical resection
      was radical in one, but palliative in the other. pTNM was T3 N0 M0, G3, R0 in the
      former and T3 N0 M0, G2 R1 in the latter. Patients died for local recurrence
      after 12 and 5 months, respectively. Natural history, clinical findings,
      prognosis and outcome of this rare gallbladder tumour are discussed on the basis
      of a review of the English literature. In conclusion, an aggressive and radical
      surgical treatment of advanced squamous and adenosquamous cell gallbladder
      carcinomas seems to be indicated for their low proclivity to distant spreading.

PMID- 15943045
TI  - A partial response in anaplastic carcinoma of the thyroid with liposomal
      doxorubicin.
AB  - Anaplastic thyroid carcinoma is a rare disease with a poor prognosis. Surgery
      represents the curative treatment for limiting the disease. In the presence of
      locoregional disease, not suitable for surgery, and for metastastic disease,
      chemotherapy represents the treatment option. Single agents chemotherapy can
      produce some responses; doxorubicin is an active drug with a rate of partial
      response lower than 20%. Association with cisplatin seems to be more active
      producing a higher rate of complete responses. Liposomal doxorubicin is a new
      class of anthracyclines, derived from a structural modification of doxorubicin,
      representing a new form of an old drug with pharmacological characteristics that
      facilitate a more easy elusion from immune system, a longer half-life, an
      increased tumor cell uptake and a reduced toxicity if compared with parental
      drug. Herein we report the first case of an anaplastic thyroid carcinoma treated
      with the use of liposomal doxorubicin. The encouraging response observed with
      single agent liposomal doxorubicin (70% according to RECIST criteria) deserves
      further investigations.

PMID- 15943046
TI  - Synchronous colon and gastric advanced carcinomas.
AB  - An unusual case of advanced synchronous colon and gastric carcinoma is described.
      A 36 year old female was admitted to our Department with a stenosing right colon
      cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain
      and gross blood in the stool. Multiple colon polyps, distal to the tumor, were
      also detected. On preoperative abdominal computed tomography, a stenosing right
      colon cancer, without evidence of abdominal diffusion, was confirmed. At
      laparotomy, in addition to colon cancer, an antral gastric cancer was
      incidentally found. En bloc hemigastrectomy and subtotal colectomy were
      performed. Digestive continuity was restored by gastrojejunal and ileosigmoid
      anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with
      signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated
      colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage
      Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2
      oncoproteins. No genetic defect was identified in the APC and MMR genes. The
      patient is alive, without recurrence, two years after the operation.

PMID- 15943047
TI  - Nothing matters.

PMID- 15943048
TI  - A new variant of the Ouchi illusion reveals Fourier-component-based processing.
AB  - We report that anomalous motion illusion in a new variant of the Ouchi figure is
      well predicted by the strength of its Fourier fundamentals and harmonics. The
      original Ouchi figure consists of a rectangular checkerboard pattern surrounded
      by an orthogonal rectangular checkerboard pattern, in which illusory relative
      motion between the two regions is perceived. Although this illusion has been
      explained in terms of biases in integrating one-dimensional motion signals to
      determine the two-dimensional motion direction, the physiological mechanism has
      not been clarified. With our new stimuli, which consisted of thin lines instead
      of rectangles, we found that the perceived illusion is drastically reduced when
      the position of each line element is randomly shifted. This is not predicted by
      simple models of local motion integration along the visible edges. We demonstrate
      that the relative amplitude of the relevant Fourier fundamentals and harmonics
      leads to a quantitative prediction. Our analysis was successfully applied to
      other variants of the Ouchi figure (Khang and Essock 1997 Perception 26 585-597),
      closely predicting the reported rating. The results indicate that the underlying
      physiological mechanism is sensitive to the Fourier components of the stimuli
      rather than the visible edges.

PMID- 15943049
TI  - Lines that induce phenomenal transparency.
AB  - Three neighbouring opaque surfaces may appear split into two layers, one
      transparent and one opaque beneath, if an outline contour is drawn that
      encompasses two of them. The phenomenon was originally observed by Kanizsa [1955
      Rivista di Psicologia 69 3-19; 1979 Organization in Vision: Essays on Gestalt
      Psychology (New York: Praeger)], for the case where an outline contour is drawn
      to encompass one of the two parts of a bicoloured figure and a portion of a
      background of lightest (or darkest) luminance. Preliminary observations revealed
      that the outline contour yields different effects: in addition to the
      stratification into layers described by Kanizsa, a second split, opposite in
      depth order, may occur when the outline contour is close in luminance to one of
      the three surfaces. An initial experiment was designed to investigate what
      conditions give rise to the two phenomenal transparencies: this led to the
      conclusion that an outline contour superimposed on an opaque surface causes this
      surface to emerge as a transparent layer when the luminances of the contour and
      the surface differ, in absolute value, by no more than 13.2 cd m(-2). We have
      named this phenomenon 'transparency of the intercepted surface', to distinguish
      it from the phenomenal transparency arising when the contour and surface are very
      different in luminance. When such a difference exists, the contour acts as a
      factor of surface definition and grouping: the portion of the homogeneous surface
      it bounds emerges as a fourth surface and groups with a nearby surface if there
      is one close in luminance. The transparency phenomena ('transparency of the
      contoured surface') perceived in this context conform to the constraints of
      Metelli's model, as demonstrated by a second experiment, designed to gather
      'opacity' ratings of stimuli. The observer judgments conformed to the values
      predicted by Metelli's formula for perceived degree of transparency, alpha. The
      role of the outline contour in conveying figural and intensity information is
      discussed.

PMID- 15943050
TI  - Novel visual illusions related to Vasarely's 'nested squares' show that corner
      salience varies with corner angle.
AB  - Vasarely's 'nested-squares' illusion shows that 90 degrees corners can be more
      salient perceptually than straight edges. On the basis of this illusion we have
      developed a novel visual illusion, the 'Alternating Brightness Star', which shows
      that sharp corners are more salient than shallow corners (an effect we call
      'corner angle salience variation') and that the same corner can be perceived as
      either bright or dark depending on the polarity of the angle (ie whether concave
      or convex: 'corner angle brightness reversal'). Here we quantify the perception
      of corner angle salience variation and corner angle brightness reversal effects
      in twelve naive human subjects, in a two-alternative forced-choice brightness
      discrimination task. The results show that sharp corners generate stronger
      percepts than shallow corners, and that corner gradients appear bright or dark
      depending on whether the corner is concave or convex. Basic computational models
      of center surround receptive fields predict the results to some degree, but not
      fully.

PMID- 15943051
TI  - Handgrip maximum force and the visual horizontal-vertical illusion.
AB  - The visual horizontal-vertical illusion (HVI) refers to the tendency to
      overestimate vertical distances relative to horizontals in both 2-D and 3-D
      presentations. Although the HVI is evident across a wide range of different
      stimuli, no general theoretical account fully explains the illusion. Some recent
      authors have proposed the 'effort' account of HVI, contending that vertical
      overestimation is mediated by effort assessment of gravitational challenges
      offered by the stimulus. The theory has been supported by a set of studies
      showing that the height overestimation of large-scale 3-D objects is inversely
      related to perceivers' fitness and strength. We explored if the large-scale
      HVI/strength dependence extends to the evaluation of small-scale 2-D line
      stimuli, traditionally used in HVI studies. We measured the maximum handgrip
      strength, and assessed the HVI with a computerised line-adjustment task in thirty
      two individuals. Compatible with earlier findings in the context of large-scale 3
      D stimuli, a significant negative correlation was found between the strength of
      the dominant hand and amount of HVI. In addition, the variability of HVI was
      negatively correlated with maximum grip strength of both hands. The results are
      discussed with reference to the 'effort' account of HVI.

PMID- 15943052
TI  - Structured perceptual input imposes an egocentric frame of reference-pointing,
      imagery, and spatial self-consciousness.
AB  - Perceptual input imposes and maintains an egocentric frame of reference, which
      enables orientation. When blindfolded, people tended to mistake the assumed
      intrinsic axes of symmetry of their immediate environment (a room) for their own
      egocentric relation to features of the room. When asked to point to the door and
      window, known to be at mid-points of facing (or adjacent) walls, they pointed
      with their arms at 180 degrees (or 90 degrees) angles, irrespective of where they
      thought they were in the room. People did the same when requested to imagine the
      situation. They justified their responses (inappropriately) by logical necessity
      or a structural description of the room rather than (appropriately) by relative
      location of themselves and the reference points. In eight experiments, we
      explored the effect on this in perception and imagery of: perceptual input
      (without perceptibility of the target reference points); imaging oneself versus
      another person; aids to explicit spatial self-consciousness; order of questions
      about self-location; and the relation of targets to the axes of symmetry of the
      room. The results indicate that, if one is deprived of structured perceptual
      input, as well as losing one's bearings, (a) one is likely to lose one's
      egocentric frame of reference itself, and (b) instead of pointing to reference
      points, one demonstrates their structural relation by adopting the intrinsic axes
      of the environment as one's own. This is prevented by providing noninformative
      perceptual input or by inducing subjects to imagine themselves from the outside,
      which makes explicit the fact of their being located relative to the world. The
      role of perceptual contact with a structured world is discussed in relation to
      sensory deprivation and imagery, appeal is made to Gibson's theory of joint
      egoreception and exteroception, and the data are related to recent theories of
      spatial memory and navigation.

PMID- 15943053
TI  - Optic-flow-based perception of two-dimensional trajectories and the effects of a
      single landmark.
AB  - Human observers can detect their heading direction on a short time scale on the
      basis of optic flow. We investigated the visual perception and reconstruction of
      visually travelled two-dimensional (2-D) trajectories from optic flow, with and
      without a landmark. As in our previous study, seated, stationary subjects wore a
      head-mounted display in which optic-flow stimuli were shown that simulated
      various manoeuvres: linear or curvilinear 2-D trajectories over a horizontal
      plane, with observer orientation either fixed in space, fixed relative to the
      path, or changing relative to both. Afterwards, they reproduced the perceived
      manoeuvre with a model vehicle, whose position and orientation were recorded.
      Previous results had suggested that our stimuli can induce illusory percepts when
      translation and yaw are unyoked. We tested that hypothesis and investigated how
      perception of the travelled trajectory depends on the amount of yaw and the
      average path-relative orientation. Using a structured visual environment instead
      of only dots, or making available additional extra-retinal information, can
      improve perception of ambiguous optic-flow stimuli. We investigated the amount of
      necessary structuring, specifically the effect of additional visual and/or extra
      retinal information provided by a single landmark in conditions where illusory
      percepts occur. While yaw was perceived correctly, the travelled path was less
      accurately perceived, but still adequately when the simulated orientation was
      fixed in space or relative to the trajectory. When the amount of yaw was not
      equal to the rotation of the path, or in the opposite direction, subjects still
      perceived orientation as fixed relative to the trajectory. This caused trajectory
      misperception because yaw was wrongly attributed to a rotation of the path: path
      perception is governed by the amount of yaw in the manoeuvre. Trajectory
      misperception also occurs when orientation is fixed relative to a curvilinear
      path, but not tangential to it. A single landmark could improve perception. Our
      results confirm and extend previous findings that, for unambiguous perception of
      ego-motion from optic flow, additional information is required in many cases,
      which can take the form of fairly minimal, visual information.

PMID- 15943054
TI  - Motion parallax driven by head movements: conditions for visual stability,
      perceived depth, and perceived concomitant motion.
AB  - Yoking the movement of the stimulus on the screen to the movement of the head, we
      examined visual stability and depth perception as a function of head-movement
      velocity and parallax. In experiment 1, for different head velocities, observers
      adjusted the parallax to find (a) the depth threshold and (b) the concomitant
      motion threshold. Between these thresholds, depth was seen with no perceived
      motion. In experiment 2, for different head velocities, observers adjusted the
      parallax to produce the same perceived depth. A slower head movement required a
      greater parallax to produce the same perceived depth as faster head movements. In
      experiment 3, observers reported the perceived depth for different parallax
      magnitudes. Perceived depth covaried with smaller parallax without motion
      perception, but began to decrease with larger parallax and concomitant motion was
      seen. Only motion was seen with the larger parallax.

PMID- 15943055
TI  - Visual impressions of interactions between objects when the causal object does
      not move.
AB  - Stimuli were presented that consisted of a stationary row of black-bordered white
      rectangles. As observers watched, each rectangle in turn from left to right
      changed from white to black. The final rectangle did not change colour but moved
      off from left to right. The sequential colour change suggested motion from left
      to right, and observers reliably reported a visual impression that this illusory
      motion kicked or bumped the last rectangle, thereby making it move. The
      impression was stronger when the sequential colour change was faster, but was not
      significantly affected by the number of the rectangles in the row (ranging from 2
      to 8). These results support the conclusion that neither contact nor motion of a
      causal object is necessary for a visual impression of causality to occur.

PMID- 15943056
TI  - [Endodontics and apical periodontitis].
AB  - The aim of this paper is to discuss the relation between root canal treatment and
      apical periodontitis (AP). AP is caused by micro organisms and is mainly a
      chronic inflammation. There is some evidence of an effect on the general health
      in immunocompromised patients. A higher incidence of AP on root filled teeth has
      been found. A number of preoperative and operative factors influence prevalence
      of AP on root filled teeth. Rubberdam placement and cleaning and shaping of the
      root canal during root canal treatment is important to create a clean canal to
      promote healing or prevent the development of AP. Placement of a good quality
      root filling and a well sealing coronal restoration are also important for the
      prevention of reinfection of the root canal. The quality of root fillings differs
      between clinical and epidemiological studies what is reflected in a lower
      prevalence of AP in the former.

PMID- 15943057
TI  - [Determination of canal length in endodontics].
AB  - Although the reliability of the electronic apex locator is agreed upon in the
      endodontic literature, the general practitioner has difficulties to integrate the
      device in his daily practice. The authors of this paper conclude that the apex
      locator should be used to confirm the information obtained from the pre-operatory
      radiograph (imperatively taken with the parallel technique) and they assert that
      the data obtained electronically have still to be interpretated. The apex locator
      can be considered an essential tool as long as its limitations are known.

PMID- 15943058
TI  - [Case report. Decompression of a periapical lesion of great size: an
      unconventional approach].
AB  - Decompression of a large periapical lesion: a modified approach. Management of
      large periapical lesions that resist conventional root canal therapy or that are
      interpreted as cystic in nature is somewhat questionable. Surgery with complete
      enucleation might be the most expeditious method of management. This approach
      however may create certain undesirable complications as compromising the vitality
      of adjacent teeth, jeopardizing their osseous support or resulting in nerve
      damage. These complications should be avoided whenever possible. A decompression
      technique can eliminate the disadvantages of enucleation by surgery. A number of
      techniques employing long-term drainage and depressurization have been described
      in the literature and have been proved to be clinically successful. The purpose
      of this case report is to describe a modified approach to the technique of
      decompression that has proved to be effective and quite comfortable for the
      patient.

PMID- 15943059
TI  - [Dens invaginatus--a challenge in endodontics].
AB  - Dens invaginatus is a malformation of teeth probably due to infolding of the
      dental papilla during tooth development. A wide range of morphologic variations
      have been described. Both coronal and radicular invaginations have been
      demonstrated. Typical characteristics associated with the coronal invagination
      are the complex anatomy and the early pulp necrosis. The etiology, epidemiology,
      classification and therapeutic considerations are reviewed.

PMID- 15943060
TI  - [Fraudulent use of digital radiographs: secret reality or fiction?].
AB  - Digital radiography has several advantages and has become an indispensable
      diagnostic tool for many dentists in daily practice. Once the digital captation
      appears on screen, the dental x-ray software allows image enhancement, to get a
      better vision and diagnosis. This image enhancement is acquired for example by
      adjusting the colour, density, sharpness, brightness or contrast. If the digital
      radiographs are exported, using various software packages created for graphic
      design and image manipulation, digital information can be altered, added or
      removed. Dental radiographs are easily duplicated, stored or spread in digital
      format. How can their authenticity be guaranteed, especially in insurance cases?
      Image enhancement features of digital radiography allow mishandling or potential
      abuse. Recently published studies illustrate the potential fraudulent use of
      digital radiography. In this article, some manipulated radiographic images are
      presented, to raise concerns about security, reliability and the potential for
      fraud.

PMID- 15943061
TI  - Bovine Chlamydophila spp. infection: do we underestimate the impact on fertility?
AB  - Classical methods for detection of Chlamydophila species, and of antibodies
      against these agents, have indicated that these bacteria are highly prevalent in
      cattle and associated with numerous disease conditions. These methods
      demonstrated acute Chlamydophila-induced diseases such as epizootic bovine
      abortion, as well as worldwide variable, but generally high, Chlamydophila
      seroprevalence. However, it was impossible to consistently detect the low levels
      of these organisms which were suspected to be present in endemic infections.
      Application of highly sensitive real-time PCR and ELISA methods for detection of
      Chlamydophila spp. DNA and of antibodies against Chlamydophila spp.,
      respectively, in a series of prospective cohort studies revealed a high
      prevalence of Chlamydophila spp. genital infections in female calves (61%) and
      adult heifers (53%). These infections were acquired by extragenital transmission
      in the first weeks of life, and infection frequency was increased by crowding of
      the animals. A challenge study demonstrated that infection with C. abortus
      resulted in decreased fertility of heifers. The experimental use of a C. abortus
      vaccine provided evidence for immunoprotection against C. abortus-induced
      suppression of bovine fertility. The results of these investigations suggest that
      bovine Chlamydophila infection should be viewed more as pervasive, low-level
      infection of cattle than as rare, severe disease. Such infections proceed without
      apparent disease or with only subtle expressions of disease, but potentially have
      a large impact on bovine herd health and fertility.

PMID- 15943062
TI  - Epidemiological investigation of Chlamydophila psittaci in pigeons and free
      living birds in Croatia.
AB  - During 2003, 278 adult pigeons (Columba livia) and 54 birds of 11 other free
      living species were caught in the various locations in the City of Zagreb,
      Croatia. Sera from 182 pigeons were tested for the presence of antibodies against
      Chlamydophila (C.) psittaci by ELISA test and 174 of them (95.6%) were found
      positive. Because of the high positivity rate in sera, cloacal swabs of 278
      pigeons as well as 54 other species of free-living birds were tested for the
      presence of C. psittaci antigen. Fourty-four of the 278 pigeons (15.83%) were
      antigen positive, whereas all 54 of the wild birds were negative. Antigen
      positive pigeons were euthanised and examined pathomorphologically and
      cytologically. Findings of specific antibodies and antigen of C. psittaci
      confirmed the high rate of infection among urban pigeons in the City of Zagreb,
      fortunately not among other free-living birds. Although the pigeon serovars of C.
      psittaci are considered to be of moderate pathogenicity for humans, the
      identification of 15.8% antigen-positive birds represents a potential source of
      infection to humans, especially for elderly people and immunodeficient patients,
      as well as for poultry in the Zagreb city area.

PMID- 15943063
TI  - Long-term study of Chlamydophilosis in Slovenia.
AB  - Immune reactivity for Chlamydophila (C.) psittaci in Slovenia was monitored in
      parrots, canaries, finches and nine species of recently captured free-living
      birds (house sparrows, Eurasian goldfinches, tree sparrows, chaffinches, European
      greenfinches, European serines, Eurasian siskins, Eurasian linnets and Eurasian
      bullfinches) in the period from 1991 to 2001. In subsequent years, specific IgG
      antibodies were found using immunofluorescence in parrots (0.7-53.6%), canaries
      (0.0-3.5%), finches (0.0-5.7%) and in captured free-living birds (33.3% of
      Eurasian goldfinches in 1994). An experimental infection with C psittaci was
      performed in order to study clinical signs and pathological changes in canaries
      and finches. The C. psittaci strain used for experimental infection was isolated
      from a cockatiel (Nymphicus hollandicus). Chlamydial DNA was extracted from
      clinical material followed by RFLP-PCR analysis. Infection of canaries and
      finches was confirmed in organ smears by direct immunofluorescence and a modified
      Gimenez staining method. In addition, serological tests of indirect
      immunofluorescence and complement fixation were applied. However, in spite of
      positive immunological reaction there were no clinical signs three weeks after
      infection. The present study includes results of a serological survey of persons
      belonging to the most important risk groups (breeders, pet shopkeepers and
      veterinarians). The results of microimmunofluorescence to identify the presence
      of specific antibodies and correlation between appearance of infection in birds
      and important risk groups are presented. Out of 143 persons belonging to the high
      risk group we found 10 (7%) persons who were immunologically positive. Testing of
      two successive samples was used to demonstrate an increase in IgG and IgA titres
      in human sera. However, IgM, which is indicative of acute infection, could not be
      detected.

PMID- 15943064
TI  - High prevalence of chlamydial (Chlamydophila psittaci) infection in fetal
      membranes of aborted equine fetuses.
AB  - Seventy-seven cases of equine abortion from 49 Hungarian farms that occurred
      between 1998 and 2000 were investigated for the presence of chlamydiae by
      immunohistochemistry, PCR and/or MZN staining. Evidence of the presence of these
      bacteria was obtained in 64 cases (83.1%) from 41 (83.7%) different farms.
      Partial ompA gene sequencing of PCR products revealed that the agent was
      Chlamydophila psittaci. Based on the findings of microbial diagnosis, pathology
      and case history, chlamydial infection was considered to be the most likely cause
      of abortion in at least 11 (14.3%) cases. In the remaining 53 Chlamydophila
      positive cases, either other bacterial and viral agents (n = 22 or 28.6%) as well
      as non-infectious factors (n = 14 or 18.2%) were identified as more probable
      primary causes of disease, or the role of chlamydiae remained unclear because
      lesions in fetuses and fetal membranes were absent (n = 17 or 22.1%). When
      chlamydial antigen was detected in aborted equine placental tissue using
      immunohistochemistry it was seen only in the chorionic epithelial cells, but not
      in other parts of the fetal membranes nor in any of the fetal tissues. In
      conclusion, chlamydial infection of the genital tract should be considered a
      possible factor in equine reproductive disorders.

PMID- 15943065
TI  - Influence of the Th2 immune response established by Nippostrongylus brasiliensis
      infection on the protection offered by different vaccines against Chlamydophila
      abortus infection.
AB  - Chlamydophila abortus is the aetiological agent of enzootic abortion in small
      ruminants in which it infects the placenta to cause abortion during the last
      trimester of gestation. In a mouse model, a Th1 immune response involving IFN
      gamma production and CD8+ T cells is necessary for the infection to be resolved.
      The authors previously demonstrated that infection with Nippostrongylus
      brasiliensis, a rodent gastrointestinal nematode extensively used in experimental
      models to induce Th2 responses, alters the specific immune response against C.
      abortus infection, increasing bacterial multiplication in liver and reducing
      specific IFN-gamma production. The aim of the present work was to clarify whether
      a Th2 immune response has any influence on the success of vaccination using both
      inactivated and attenuated vaccines. The results showed that the Th2 response
      established prior to vaccination did not influence the induction of protection
      offered by the vaccines. However, the effectiveness of this protective response
      can be altered, depending on the adjuvant employed in the inactivated vaccines,
      when the Th2 response is established after vaccination, just before challenge
      with C. abortus.

PMID- 15943066
TI  - Development of a hamster model of Chlamydophila pneumoniae infection.
AB  - The aim of this study was to develop a new experimental model of Chlamydophila
      pneumoniae infection in the hamster. Intraperitoneal injection of C. pneumoniae
      purified elementary bodies (EBs) in the hamsters caused a systemic infection,
      since it was possible to isolate viable chlamydiae from several organs up to 14
      days after infection. In particular, spleen infection was detectable up to 7 days
      post infection in 100% of animals. In contrast, cultures of the organs obtained
      from intranasally infected animals were far less frequently positive. Systemic
      infection probably occurred via macrophages, as demonstrated by the presence of
      intracellular chlamydial inclusions in peritoneal macrophages of peritoneally
      inoculated animals four days after infection. Furthermore, by infecting LLC-MK2
      cells with supernatant preparations obtained from these macrophages, it was
      possible to observe the development of chlamydial intra-cytoplasmic inclusions
      after 96 h. Immunization of 18 hamsters with heat-inactivated purified EBs
      completely protected 16 animals and substantially reduced infection levels in the
      remaining two. Sera obtained from immunized hamsters prior to challenge reacted
      mainly against two C. pneumoniae proteins of about 60 kDa, when tested by
      immunoblot.

PMID- 15943067
TI  - Evidence of infection in tortoises by Chlamydia-like organisms that are
      genetically distinct from known Chlamydiaceae species.
AB  - Nasal lavage fluid was collected from 155 tortoises, mostly Testudo spp., that
      were kept as companion animals and suffered from nasal discharge. Examination for
      chlamydial DNA by PCR assays targeting the ompA, ompB, and groESL genes, as well
      as the 16S rRNA signature region and the 16S-23S intergenic spacer, respectively,
      revealed 16 (10.3%) positive animals. Sequence analysis of PCR products indicated
      high homology to the family Chlamydiaceae. Phylogenetic trees constructed from
      partial sequences of the ompA and 16S rRNA genes showed that the present samples
      clustered outside the nine species of Chlamydia and Chlamydophila. Sequences of
      the nearest relative, Chlamydophila pecorum, were still clearly distinct from
      those of the positive tortoise samples. This suggests that the tortoises had been
      infected by Chlamydia-like agents, the taxonomic identity and pathogenic
      importance of which has yet to be established.

PMID- 15943068
TI  - Rechallenge of previously-infected pregnant ewes with Chlamydophila abortus.
AB  - In an attempt to ascertain the means whereby previous exposure to Chlamydophila
      (C.) abortus can protect against the re-occurrence of enzootic abortion of ewes
      (EAE), ten previously-exposed ewes were intravenously rechallenged with a large
      infective dose of C. abortus during pregnancy. The patterns of development of
      chlamydial placentitis and its sequelae closely resembled that observed following
      first-time challenge of previously-naive ewes, although placentitis appeared to
      develop more slowly following rechallenge infection and none of the rechallenged
      ewes aborted. Chorioallantoic and foetal pathology and foetal immune responses
      were qualitatively similar whilst the local maternal response to C. abortus
      infection of the endometrium did not appear to differ in rechallenged and first
      time challenged sheep. This demonstrates that if C. abortus reaches the foetal
      side of the placenta, a stereotypical response is elicited, regardless of the
      status of maternal immunity. Therefore it appears that in natural circumstances,
      acquired immunity of the dam protects against the re-occurrence of EAE by
      preventing the causative agent from reaching the susceptible foetal trophoblast.

PMID- 15943069
TI  - Diagnosis of ovine chlamydial abortions by PCR-RFLP performed on vaginal swabs.
AB  - Ovine enzootic abortion is an infectious and contagious disease clinically
      characterized by abortion and weak neonates, affecting sheep and goats. The
      etiological agent is Chlamydophila (C.) abortus, which is considered one of the
      most common animal pathogens of small ruminants; it has important economic
      implications and represents a significant zoonotic risk. Clinical diagnosis is
      often difficult because the clinical signs and the pathological lesions are not
      specific for C. abortus infection, in fact they can also be observed as a result
      of infections with other abortifacient agents. Moreover, the involvement of the
      laboratory is necessary to perform the definitive diagnosis. One hundred and
      seventeen vaginal swabs from sheep with clinical signs related to chlamydial
      infection were examined by a PCR-RFLP assay that demonstrated high specifity and
      sensitivity. Six samples were positive for C. abortus. Vaginal swabs are easy to
      handle and allow to deal with biohazardous material in safety conditions.

PMID- 15943070
TI  - Detection of Chlamydophila abortus in sheep and goat flocks in southern Italy by
      PCR using four different primer sets.
AB  - An epidemiological survey was performed to detect the presence of Chlamydophila
      (C.) abortus and other members of the order Chlamydiales in ovine and caprine
      flocks with a history of abortion in southern Italy. Four pairs of primers were
      compared to evaluate their ability to detect Chlamydiales using purified DNA
      preparations and tissue samples from aborted foetuses with suspected chlamydial
      infections. As expected, amplification of DNA of the reference strain C. abortus
      using primer pairs U23F/23Sigr, 16SF2/23R, CTU/CTL and CpsiA/CpsiB produced
      fragments of about 600 bp, 585 bp, 1000 bp and 300 bp, respectively. The
      detection limits of the four PCR tests performed on serial DNA dilutions of the
      C. abortus reference strain were of 10 pg, 0.1 pg, 0.1 pg and 1 fg of DNA,
      respectively. The most sensitive amplification of DNA extracted from the organ
      tissues was obtained with primer pairs CpsiA/CpsiB, which detected Chlamydophila
      spp. DNA in all infected tissue samples. Only C. abortus was identified during
      the survey. The presence of this agent was confirmed in 3 out of 27 ovine and
      caprine flocks included in the survey suggesting that abortion due to C. abortus
      is uncommon in southern Italy.

PMID- 15943071
TI  - Role of Chlamydophila abortus in ovine and caprine abortion in Sardinia, Italy.
AB  - Between 1999-2003, 14321 sera and 646 abortion samples (498 foetuses and 148
      placentae) were analysed from 807 sheep and goat farms distributed all over the
      island of Sardinia. After notification of abortion in a flock, sera collected at
      random from adult animals were examined to detect antibodies specific to
      Chlamydophila (C.) abortus by ELISA, whereas foetuses and placenta were analysed
      by PCR assay. Specific IgG antibodies were detected in 611 (4.8%) sheep and 106
      (5.8%) goats. From a total of 2050 ovine and 151 caprine fetal samples including
      muscle, liver, abomasum, spleen, brain and placenta, 29 (1.4%) ovine and 1 (0.6%)
      caprine samples were C. abortus PCR-positive. Placenta was the tissue with the
      highest detection rate. These results indicate that the seroprevalence of C.
      abortus infection in sheep and goats is very low in Sardinia, and PCR results
      demonstrate that C. abortus has no significant role in abortion, especially in
      goats.

PMID- 15943072
TI  - Evaluation of lung function in pigs either experimentally or naturally infected
      with Chlamydiaceae.
AB  - This study evaluated the influence of chlamydial infections on lung function in
      conventionally raised pigs. Eight pigs aged 39-44 days were included in an
      aerogeneous challenge model (4 were exposed to Chlamydia suis; 4 served as
      controls). Nineteen pigs aged 5-27 weeks without clinical symptoms (but partly
      PCR-positive for chlamydial species) were examined over 6 months. For lung
      function testing, impulse oscillometry was used. In total, all 27 pigs underwent
      465 lung function tests. Variables of ventilation (respiratory rate, tidal
      volume, minute volume), respiratory impedance (expressed as resistance and
      reactance within the frequency range 3-15 Hz), and model derived resistance of
      proximal and distal airways were measured. Experimental exposure to C. suis
      significantly affected lung function. Early distal airway obstruction (3-5 days
      after infection) was followed by an obstruction of proximal airways (7 days after
      infection). The breathing pattern was significantly changed (decreased tidal
      volume; increased respiratory rate). In symptom-free pigs having a naturally
      acquired presence of different chlamydial species in the respiratory system, no
      deterioration in lung function could be determined up to the age of 6 months. In
      conclusion, the consequences of respiratory chlamydial infections appear to vary
      from clinical inapparence to severe respiratory distress.

PMID- 15943073
TI  - Ovine enzootic abortion (OEA): antibody response in vaccinated sheep compared to
      naturally infected sheep.

PMID- 15943075
TI  - Managing acute otitis media in children with tympanostomy tubes. Panel
      discussion.

PMID- 15943074
TI  - Evaluation of an automated complement fixation test (Seramat) for the detection
      of chlamydial antibodies in sheep and goat sera.

PMID- 15943076
TI  - [The three revolutions of histology].

PMID- 15943077
TI  - [Endoscopic ventricular anatomy].
AB  - Neurosurgical endoscopy enables in situ exploration of the dilated ventricular
      system, primarily for therapeutic rather than diagnostic purposes.
      Ventriculocisternostomy in patients with obstructive hydrocephalus is the most
      widely performed endoscopic procedure. Perfect knowledge of the intraventricular
      anatomy is necessary for proper endoscopic navigation so the operator always
      recognizes the position of the endoscope and the anatomic structures encountered.
      Endoscopic anatomy in this situation is different from normal anatomy because of
      the hydrocephalus. Anatomic landmarks must be reassessed. We present here this
      "new" anatomy.

PMID- 15943078
TI  - Microscopic morphology and histology of the human meninges.
AB  - The meninges comprise the dura mater and the leptomeninges (arachnoid and pia
      mater). Dura forms an outer endosteal layer related to the bones of the skull and
      spine and an inner layer closely applied to the arachnoid mater. Leptomeninges
      have multiple functions and anatomical relationships. The outer parietal layer of
      arachnoid is impermeable to CSF due to tight intercellular junctions; elsewhere
      leptomeningeal cells form demosomes and gap junctions. Trabeculae of
      leptomeninges compartmentalize the subarachnoid space and join the pia to
      arachnoid mater. In bacterial meningitis leptomeningeal cells secrete cytokines.
      Pia mater is reflected from the surface of the brain and spinal cord onto
      arteries and veins, thus separating the subarachnoid space from the brain and
      cord. A sheath of leptomeninges accompanies arteries into the brain and is
      related to the pathways for the drainage of interstitial fluid that play a role
      in inflammatory responses in the brain and appear to be blocked by amyloid-beta
      in Alzheimer's disease. Specialised leptomeningeal cells in the stroma of the
      choroid plexus form collagen whorls that become calcified with age.
      Leptomeningeal cells also form channels in the core and apical cap of arachnoid
      granulations for the drainage of CSF into venous sinuses. In the spine,
      leptomeninges form highly perforated intermediate sheets of arachnoid and
      delicate ligaments that compartmentalize the subarachnoid space; dentate
      ligaments anchor subpial collagen to the dura mater and stabilize the spinal
      cord. Despite the multiple anatomical arrangements and physiological functions,
      leptomeningeal cells retain many histological features that are similar from site
      to site.

PMID- 15943079
TI  - [The meninges, an anatomical point of view].
AB  - The meninges correspond to an anatomical concept. For the morphologist, the
      microscopic organization, the hypothetical presence of a subdural space, the
      nature of the interface between the deep meningeal layer and the nervous
      parenchyma in the perivascular spaces are the central issues. For the clinician,
      dynamic aspects of cerebrospinal fluid flow, secretion, and resorption are
      essential factors with practical consequences in terms of disease and patient
      management. Comparative anatomy, embryology, and organogenesis provide an
      interesting perspective for the descriptive and functional anatomy of the
      meninges. Usually considered as protective membranes, the meninges play a
      prominent role in the development and maintenance of the central nervous system.
      The meninges are in constant evolution, from their formation to senescence. The
      meninges present three layers in children and adults: the dura mater, the
      arachnoid and the pia mater. The cerebrospinal fluid is secreted by the choroid
      plexuses, flows through the ventricles and the subarachnoid space, and is
      absorbed by arachnoid granulations. Other sites of secretion and resorption are
      suggested by comparative anatomy and human embryology and organogenesis.

PMID- 15943080
TI  - [Anatomical basis of the extraspinal cord compression].
AB  - Knowledge of anatomical landmarks of the spinal cord within the vertebral foramen
      is essential to understand the pathogenesis of spinal cord compression by tumor
      growth. The spinal cord can spread in the intervertebral foramen, the epidural
      space, the vertebral body, and the posterior neural arch. The morphology of the
      spinal cord, the relations of the spinal roots with the vertebrae, the principal
      fiber tracts, the spinal membranes, and the arterial and venous distribution are
      described in order to explain and analyze signs and disorders caused by the most
      frequent tumors involved in spinal cord compression.

PMID- 15943082
TI  - Fractal fracas.

PMID- 15943081
TI  - [Where have the neuronal stem cells of the subependymal zone gone in human
      beings?].
AB  - Stem cells are characterized by their ability for self-renewal (allowing them to
      be present throughout the entire life of the organism) and their ability to give
      rise to differentiated cells belong to one or more lineages. The strict
      definition of these cells is however still a matter of debate. There is new
      experimental evidence (including in human beings) that stem cells are present
      within the brain and may give rise to neurons. Ependymal cells have been proposed
      to play such a role. In fact, subependymal cells expressing GFAP would be more
      likely candidates. Such cells are observed in the brain of human beings. They are
      able to differentiate into neurons in vitro but such potential appears to be
      repressed in vivo.

PMID- 15943083
TI  - Do you see what I mean?

PMID- 15943084
TI  - The Delta3D open source game engine.

PMID- 15943085
TI  - Forget the funny glasses.

PMID- 15943086
TI  - Detail preserving reproduction of color images for monochromats and dichromats.

PMID- 15943087
TI  - Depicting dynamics using principles of visual art and narrations.

PMID- 15943088
TI  - Visualizing live text streams using motion and temporal pooling.

PMID- 15943089
TI  - Medial-axis-based cartograms.

PMID- 15943090
TI  - Visualizing spatial multivalue data.

PMID- 15943091
TI  - Thoughts on the state of 3D CG in film and video.

PMID- 15943092
TI  - Vectors and geometry and objects, oh my!

PMID- 15943093
TI  - [Image of the month. Defect of the lower segment of the uterus after cesarean
      section, detected with contrast hysterosonography].

PMID- 15943094
TI  - [How I treat ... basal cell carcinoma by imiquimod].
AB  - Basal cell carcinoma is the most frequent cancer in humans. Several clinical
      types are distinguished. They are bound to distinct evolutive prognosis. The
      surgical excision is the treatment of choice which is rarely followed by
      recurrence. However, when the lesion is superficial and non aggressive and when
      the body site is adequate, topical applications of imiquimod can provoke the
      neoplastic regression. This type of immunotherapy brings 70 to 90% complete
      remission. A medical follow-up of the treated site is mandatory for a couple of
      years.

PMID- 15943095
TI  - [Place of ivermectin in the treatment of scabies].
AB  - Ivermectin is the first oral treatment available for scabies. It is however not
      licensed for use in Belgium. In this article, we review its mechanism of action,
      its preferential indications among which crusted scabies and institutional
      outbreaks, its contra-indications and its advantages in comparison with topical
      treatments.

PMID- 15943096
TI  - [Congenital pericardial defect associated with coronary artery disease: surgical
      treatment].
AB  - The case of a 62-year-old patient presenting with exertional chest pain,
      atheromatous coronary lesions and left congenital pericardial defect is reported.
      The diagnostic of peri cardial defect was evoked in relation with a long-known
      asymptomatic cardiac left malposition and confirmed at surgery. Clinical
      presentation, diagnosis and management of congenital pericardial defects are
      discussed.

PMID- 15943097
TI  - [Arsenical keratoses and carcinomas].
AB  - We report the case of a 70-year old man who presented the classical cutaneous
      signs of chronic arsenicism : palmo-plantar keratoses and lesions of Bowen's
      disease. Within a few months, the patient developed multiple large superficial
      basal cell carcinomas on the trunk and several invasive squamous cell carcinomas.
      A pulmonary cancer with cerebral metastases was also identified. The
      complications of chronic arsenicism are nowadays rarely encountered. The
      cutaneous changes should be recongized because they allow to reveal the etiology
      of some internal lesions. Indeed, the notion of past arsenicism is often missing
      in the patient records. The recognition of the cutaneous warning signs allows to
      focus on the overall cancer risk of these patients.

PMID- 15943098
TI  - [Hyperkalemia: the new killer?].
AB  - Hyperkalemia is now commonly observed due to several associated factors such as
      old age, diabetes, congestive heart failure, renal insufficiency and drugs such
      as spironolactone used to improve cardiac function. Moreover, the easily
      prescribed new antiinflammatory drugs COX2 selective inhibitors in these patients
      lead to a very acute risk for vital hyperkalemia development. This review insists
      on the prevention of such potentially reversible disorder.

PMID- 15943099
TI  - [Depenalized practice of euthanasia in Belgium].
AB  - The first report of the federal commission of control and evaluation of
      euthanasia, transmitted to Parliament on September 17, 2004, gives interesting
      data concerning the practice of euthanasia in Belgium under the conditions
      specified by the law of May 28, 2002. The present paper analyses and comments
      upon this report.

PMID- 15943100
TI  - [The first gynecological consultation in teens].
AB  - The first gynecological consultation is particularly important for teens. It not
      only allows to answer the patient's questions, for instance, by prescribing a
      contraception, but also to provide an adequate information about some subjects,
      including sexuality, sexually transmitted diseases, and some life-style habits.
      This article will review the various important points of this first consultation.

PMID- 15943101
TI  - [Inflammation and atherosclerosis: state of the art in 2004-2005].
AB  - Inflammation plays a pivotal role in atherosclerosis; being present in all steps
      of the pathology, from initiation to the progression of the lesions to the
      development of vulnerable plaques and clinical destabilisation. Therefore,
      systemic markers of inflammation have emerged to predict future cardiovascular
      events in patients initially admitted for unstable syndromes, but also in healthy
      subjects. These markers can identify high risk patients and they are used to
      adapt ideal treatment to the patient's profile. The implication of the
      inflammation process in the treatment strategies is described in the last part of
      the article.

PMID- 15943102
TI  - [Some trouble in the field of onychomycosis].
AB  - Recently, onychomycoses raised some interest from groups whose business is
      communication to the public. The combination of commercial interest, dogmatism
      and disinformation appears to have found there a potentially damaging field of
      action. This review is an attempt to shed some light on this topic using
      objective and qualified medical information.

PMID- 15943103
TI  - [Acute limb ischemia: clinical, diagnostic and therapeutic aspects].
AB  - Acute lower limb ischemia, with sudden interruption of tissue perfusion, is a
      medico-surgical emergency. An early diagnosis is a prerequisite for optimal
      management. Diagnosis is mainly based on clinical data. Complementary
      investigations have a limited place, and should not unnecessarily delay the
      treatment. There are two categories of acute arterial, non-traumatic occlusion:
      embolism and thrombosis of an atherosclerotic vessel. The distinction between
      these two entities is not always evident, since ischemia can be the consequence
      of an arterial embolism in a diseased atherosclerotic artery. We discuss the
      clinical aspects and the causes of acute lower limb ischemia. The prognosis,
      outcome and therapeutic management are determined by the cause of the acute
      arterial obliteration.

PMID- 15943104
TI  - [Hypertension due to primary aldosteronism].
AB  - Primary aldosteronism is a rare cause of hypertension. However, its incidence
      seems to be underestimated. It is important to identify this syndrom since the
      disease is potentially curable. In the present paper, we depict different forms
      of primary aldosteronism as well as the diagnostic procedures. When the diagnosis
      is suspected (hypertension associated to spontaneous or diuretic-induced
      hypokaliemia), the more efficient screening test is the determination of the
      aldosteron/renin ratio. Saline infusion or posture tests can thereafter confirm
      the diagnosis. Differential diagnosis between bilateral and unilateral forms of
      primary aldosteronism can be made by CT-scanner and the response of aldosterone
      to the posture test. Such a complex assessment leads to the identification of
      patients who can be surgically treated. This treatment consists in a unilateral
      adrenalectomy which can be realised by laparoscopy.

PMID- 15943105
TI  - ["Treating to New Targets": plea for a LDL cholesterol target of or below 75
      mg/dl in any patient with coronary heart disease].
AB  - The "Treating to New Targets" (TNT) trial compared atorvastatin 80 mg (aiming at
      reducing LDL cholesterol < or = 75 mg/dl) and atorvastatin 10 mg (LDL < or = 100
      mg/dl as target) in 10,001 patients with stable coronary heart disease followed
      up for 5 years. A reduction of major cardiovascular events of 22% was observed in
      the atorvastatin 80 mg group as compared to the atorvastatin 10 mg group (hazard
      ratio: 0.78; 95 % interval of confidence: 0.69-0.89; p < 0.001). Such clinical
      efficacy was obtained while a good drug safety profile was maintained. Total
      mortality was not significantly different between the two groups. However, and
      remarkably, cardiovascular death was not the first cause of death anymore in this
      atorvastatin-treated population. The results of TNT in patients with stable
      coronary heart disease thus confirm the results of PROVE-IT in patients with
      acute coronary syndrome. These two randomised controlled trials should encourage
      considering a LDL cholesterol level of 75 mg/dl (rather than 100 mg/dl) as a new
      target in any patient with coronary heart disease.

PMID- 15943106
TI  - Identification of bacteria isolated from an oligotrophic lake with pesticide
      removal capacities.
AB  - We studied the growth and capacities for pesticides removal of bacterial strains
      isolated from the Laguna Grande, an oligotrophic lake at the South of Spain
      (Archidona, Malaga). Strains were isolated from water samples amended with 10 and
      50 microg/ml of nine pesticides: organochlorinated insecticides (aldrin and
      lindane), organophosphorous insecticides (dimetoate, methyl-parathion and
      methidation), s-triazine herbicides (simazine and atrazine), fungicide (captan)
      and diflubenzuron (1-(-4-chlorophenyl)-3-(2,6-difluorobenzoyl urea), a chitinase
      inhibitor. The majority of the strains belonged to the genera Pseudomonas and
      Aeromonas and only 9% of the total of strains were Gram positive. From all the
      strains isolated, only 22 showed a wide growth range in all the pesticides tested
      and 4 of them were chosen for pesticide removal studies. The genetic
      identification of these strains showed their affiliation to Pseudomonas
      pseudoalcaligenes, Micrococcus luteus, Bacillus sp. and Exiguobacterium
      aurantiacum. These last two strains were those that showed the highest pesticide
      removal capacities and a high bacterial growth.

PMID- 15943107
TI  - Developmental responses of a terrestrial insect detritivore, Megaselia scalaris
      (Loew) to four selenium species.
AB  - Megaselia scalaris (Loew) (Diptera: Phoridae) is an important and ubiquitous
      terrestrial detritivore that consumes both animal and plant material. Because
      both plants and animals convert selenium pollutants into various forms, the
      relative toxicities of ecologically relevant concentrations of sodium selenate,
      sodium selenite, seleno-L-methionine, and Se-(methyl) selenocysteine
      hydrochloride to larvae were assessed in diet bioassays. In addition,
      ovipositional preferences of adults and developmental effects on the eggs and
      larvae were measured. With chronic exposure selenocysteine was the most toxic of
      the selenium species to the larvae (LC50: 83 microg/g wet weight), followed by
      seleno-L-methionine (LC50: 130 microg/g), selenate (LC50: 258 microg/g), and
      selenite (LC50: 392 microg/g). Ovipositing females did not discriminate between
      the highest treatment concentrations of any of the pollutants as compared to the
      controls, indicating a lack of avoidance behavior. Larval development time was
      significantly increased with exposure to selenate at 100 microg/g wet weight and
      above, selenite at 300 microg/g and above, and at 50 microg/g and 25 microg/g and
      above for seleno-L-methionine and selenocysteine respectively. Pupal development
      was not affected by any of the selenium treatments. Significant differences
      between male and female adult eclosion times were observed, with females eclosing
      later than males as selenium concentrations increased. Significant decreases in
      larval survival relative to controls occurred at the lowest treatment tested (100
      microg/g) for both selenate and selenite and at 100 microg/g for seleno-L
      methionine, and 50 microg/g for selenocysteine. The population level implications
      of lack of avoidance of contaminated food, and the effects of increased
      development times, reduced survivorship, and non-synchronized male and female
      emergence are discussed.

PMID- 15943108
TI  - Use of comet and micronucleus assays to measure genotoxicity in meadow voles
      (Microtus pennsylvanicus) living in golf course ecosystems exposed to pesticides.
AB  - The purpose of this study was to conduct a biomonitoring study to measure the
      effects of pesticide exposure in meadow voles (Microtus pennsylvanicus) living in
      golf courses of the Ottawa/Gatineau region of Canada. In this article we present
      the results from the comet and micronucleus assay. Voles were captured in 2001
      and 2002 at five golf courses and two reference sites. Blood was collected from
      sedated voles. Three animals from each course were euthanized to determine body
      burdens of historically used organochlorine (OC) and metal-based pesticides.
      Exposure to in-use pesticides was determined from detailed golf course pesticide
      use records. Comet tail length and tail moment were not related to body burdens
      of OC pesticides and metals historically used on these golf courses. In
      generally, tail length and moment significantly decreased in relation to days
      since last application of a pesticide, and to days since the last application of
      a specific fungicide (Daconil) containing a potentially genotoxic active
      ingredient (chlorothalonil). The slopes of these curves in 2002 were not
      significantly different than the half-life decay curve of chlorothalonil on
      vegetation. Both comet assay parameters appeared to increase in a dose-dependent
      manner with the amount of the last application Daconil. The number of
      micronucleated polychromatic erythrocytes was not related to any pesticide
      application parameter.

PMID- 15943109
TI  - Toxicity of organic compounds to marine invertebrate embryos and larvae: a
      comparison between the sea urchin embryogenesis bioassay and alternative test
      species.
AB  - This study investigated the toxic effects of the insecticides lindane and
      chlorpyrifos, the herbicide diuron, the organometallic antifoulant tributyltin
      (TBT), and the surfactant sodium dodecyl sulfate (SDS) on the early life stages
      of Paracentrotus lividus (Echinodermata, Euechinoidea), Ciona intestinalis
      (Chordata, Ascidiacea), Maja squinado and Palaemon serratus (Arthropoda,
      Crustacea) in laboratory acute toxicity tests. The assays studied embryogenesis
      success from fertilized egg to normal larvae in P. lividus (48 h incubation at 20
      degrees C) and C. intestinalis (24 h incubation at 20 degrees C), and larval
      mortality at 24 and 48 h in M. squinado and P. serratus. For P. lividus, the
      median effective concentrations (EC50) reducing percentages of normal larvae by
      50% were: 350 microg l(-1) for chlorpyrifos, 5500 microg l(-1) for diuron, 4277
      microg l(-1) for SDS, and 0.309 microg l(-1) for TBT. For C. intestinalis, the
      EC50 values affecting embryogenesis success were 5666 microg l(-1) for
      chlorpyrifos, 24,397 microg (l-1) for diuron, 4412 microg l(-1) for lindane, 5145
      microg I(-1) for SDS, and 7.1 microg l(-1) for TBT. The median lethal
      concentrations (LC50) for M. squinado larval survival were 0.84 microg l(-1) (24
      h) and 0.79 microg l(-1) (48 h) for chlorpyrifos, 2.23 microg(l(-1) (24 h) and
      2.18 microg l(-1) (48 h) for lindane, and 687 microg l(-1) (48 h) for SDS. For P.
      serratus the LC50 values obtained were 0.35 microg l(-1) (24 h) and 0.22 microg
      l(-1) (48 h) for chlorpyrifos, 3011 microg l(-1) (24 h) and 3044 microg l(-1) (48
      h) for diuron, 5.20 microg l(-1) (24 h) and 5.59 microg l(-1) (48 h) for lindane,
      and 22.30 microg l(-1) (24 h) and 17.52 microg l(-1) (48 h) for TBT. Decapod
      larvae, as expected, were markedly more sensitive to the insecticides than sea
      urchins and ascidians, and SDS was the least toxic compound tested for these
      organisms. Lowest observed effect concentrations (LOEC) of TBT for sea urchin and
      ascidian embryos, chlorpyrifos and lindane for crustacean larvae, and SDS, were
      similar to those found in many coastal areas indicating that there would be a
      risk to invertebrate embryos and larvae from exposure in the field to these
      pollutants.

PMID- 15943110
TI  - Threshold levels for effects of insecticides in freshwater ecosystems: a review.
AB  - A literature review of freshwater (model) ecosystem studies with neurotoxic
      insecticides was performed to assess ecological threshold levels, to compare
      these levels with the first tier approach within European Union (EU)
      administration procedures, and to evaluate the ecological consequences of
      exceeding these thresholds. Studies published between 1980 and 2001 were
      reviewed. Most studies covered organophosphates and synthetic pyrethroids in
      lentic waters. The most sensitive taxa were representatives of crustaceans,
      insects and fish. Based on toxic units, threshold values were equivalent for
      compounds with a similar mode of action. This also accounted for the nature and
      magnitude of direct effects at higher concentrations. Although laboratory single
      species toxicity tests may not allow predictions on precise ecological effects,
      some generalisations on effects and recovery can be made with respect to acute
      standard laboratory EC50 data. The NOEC(ecosystem) usually is a factor of 10 or
      more higher than first tier acceptable concentrations, particularly in the case
      of single applications and acetylcholinesterase inhibitors. Acceptable
      concentrations, as set by the EU first tier approach, appear to be protective.
      Recovery of sensitive endpoints usually occurs within 2 months of the (last)
      application when peak concentrations remain lower than (0.1-1) x EC50 of the most
      sensitive standard test species. The consistency of response patterns found in
      model ecosystem studies can be useful when estimating the ecological risks of
      pesticides. The use of an effect classification system was also helpful in
      evaluating effects.

PMID- 15943111
TI  - Thyroid function in nestling tree swallows and eastern bluebirds exposed to non
      persistent pesticides and p, p'-DDE in apple orchards of southern Ontario,
      Canada.
AB  - This study examined the associated effects of pesticides and persistent residues
      of p,p'-DDE on thyroid function in 16-day-old tree swallows (Tachycineta bicolor)
      and 12-day-old eastern bluebirds (Sialia sialis). Apple orchards sprayed with
      pesticides in current use and reference sites were chosen for study in southern
      Ontario, Canada, during 2000-2001. We assessed thyroid hormone concentrations
      (plasma and muscle thyroxine [T4], and triiodothyronine [T3]) and the response to
      a challenge with thyroid stimulating hormone (TSH) as well as parameters of
      thyroid histology. Individual nests were exposed to as many as seven individual
      pesticide applications and up to five pesticide mixtures. Concentrations of p,p'
      DDE in eggs from both species were highest in orchard sites, and ranged from 0.05
      to 5.44 mg/kg wet weight for tree swallows, and from 0.17 to 95.4 mg/kg for
      eastern bluebirds. In 2000, tree swallows from sprayed orchards had elevated
      plasma T4 concentrations, and thyroid glands with collapsed follicles,
      hypertrophic epithelia, and higher follicular epithelial cells relative to chicks
      from reference sites. Plasma T4 concentration was positively correlated with the
      total number of pesticide mixtures applied during egg incubation through chick
      rearing. In 2001, basal plasma T3 concentration in tree swallow chicks did not
      differ between orchard and reference sites, though there were differences among
      orchards; T3 was positively correlated with total number of individual sprays
      applied during egg incubation through chick rearing. Tree swallows challenged
      with TSH showed no significant difference in thyroid hormone concentration or
      follicular epithelial cell height between exposure groups; however, a
      significantly greater proportion of chicks from reference sites were found to
      have thyroids with focal or diffuse hypertrophic epithelia relative to orchard
      chicks. In 2001, bluebirds from sprayed orchards had significantly higher T3
      concentrations in response to TSH challenge; this response was positively
      correlated with the total number of pesticides applied during egg incubation
      through chick rearing.

PMID- 15943112
TI  - Environmental impacts of diesel fuel on bacteria and phytoplankton in a tropical
      estuary assessed using in situ mesocosms.
AB  - Dissolved or dispersed petroleum hydrocarbon concentrations (DDPH) were monitored
      in Ponggol estuary, Singapore, fortnightly from July 1999 to June 2000. DDPH
      concentrations ranged from 4.4 to 248.9 microg l(-1) and 0.4 to 1099.7 microg l(
      1) for surface and subsurface waters, respectively and with mean concentrations
      of 41.01 microg l(-1) in the water column. Absorbed or adsorbed petroleum
      hydrocarbon (AAPH) concentrations measured in sediments ranged from 20.6 to 541.0
      mg kg(-1), with mean concentrations of 148.23 mg kg(-1). In situ mesocosm studies
      of bacteria and phytoplankton were based on field monitoring of environmentally
      measured concentrations of petroleum hydrocarbons, using diesel fuel as the
      source of contaminant. The mesocosm comprised of 25 L clear polycarbonate carboys
      incubated in situ for 6 days. Water and sediments from a clean site with
      undetectable levels of petroleum hydrocarbons were used in controls. The
      treatment mesocosms comprised of mean and highest concentrations of DDPH and
      AAPH. The study revealed signs of acute toxicity to autotrophs viz.,
      phytoplankton and autotrophic bacteria in treatments simulating concentrations of
      diesel fuel found in the sediments. A stimulatory effect was seen at lower
      concentrations. Bacterial heterotrophs responded positively to all concentrations
      of diesel fuel because of the abundance of a carbon source, reduced grazing
      pressure and reduced competition for nutrients from phytoplankton.

PMID- 15943113
TI  - Comments on animal health and welfare issues not germane to a commentary on the
      morality of increased salaries for veterinarians.

PMID- 15943114
TI  - Antiobiotic responsive neuromuscular (cerebral) ataxia.

PMID- 15943115
TI  - An ethicist's commentary on a veterinarian's obligation to treat stray barn cats.

PMID- 15943116
TI  - Highlights of camelid diagnoses from necropsy submissions to the Animal Health
      Laboratory, University of Guelph, from 1998 to 2004.

PMID- 15943117
TI  - Chronically starved horses: predicting survival, economic, and ethical
      considerations.
AB  - Nine of 45 horses subjected to prolonged malnutrition died subsequent to being
      placed with a responsible caregiver and being provided an appropriate diet.
      Initial extreme poor body condition score tended to be associated with death,
      although individual response to refeeding varied. The financial costs of
      stabilizing the group of horses significantly exceeded their free market price.
      Responsible management of chronically starved commercial animals should include
      options for immediate euthanasia.

PMID- 15943118
TI  - A retrospective study of the diagnoses and survival of elk admitted to a large
      animal referral clinic.
AB  - Information for veterinarians regarding diseases of farmed elk remains scarce
      despite an increase in the size of the industry. This retrospective study
      examines all (n=245) elk cases admitted to the Western College of Veterinary
      Medicine over an 11-year period (1991 to 2001). Age, gender, date of admission,
      diagnosis, and outcome were examined. Diarrhea, fractures, and other
      musculoskeletal problems were most common. Most (76%) cases involved elk under 1
      y of age; these were more commonly diagnosed with fractures or diarrheal disease.
      Elk older than 1 y of age tended to be diagnosed with fractures or noninfectious
      diseases. Overall, the most common diagnosis was fractures, which were seen
      mostly as traumatic catastrophic long bone fractures. Fractures and other
      musculoskeletal problems occurred towards the end of summer and into the fall,
      while diarrhea and other infectious diseases were diagnosed in young elk in the
      spring and summer. The in-hospital case fatality rate was 33.5%.

PMID- 15943119
TI  - Adenomyosis with severe inflammation in the uterine cervix in a dog.
AB  - A dog with purulent vulval discharge was found to have many cysts containing
      purulent mucus in the uterine cervix. The uterine horns did not contain any pus.
      Histological examination revealed a cervical adenomyosis infiltrated by many
      neutrophils. After an ovariohysterectomy including the whole cervix, the dog
      recovered well.

PMID- 15943120
TI  - Insulinoma in 2 guinea pigs (Cavia porcellus).
AB  - This paper describes an insulinoma in 2 guinea pigs (Cavia porcellus). Both
      guinea pigs presented with neurologic signs and low blood glucose readings. The
      neurologic signs resolved with dextrose administration. Insulinoma was confirmed
      on postmortem examination.

PMID- 15943121
TI  - Congenital aganglionosis in a 3-day-old Holstein calf.
AB  - Necropsy of a 3-day-old Holstein heifer revealed proximal megacolon and distal
      colorectal hypoplasia. Histologically, the hypoplastic distal colon and rectum
      lacked submucosal and myenteric ganglia. Clinical history, physical examination,
      and pathologic findings were consistent with intestinal aganglionosis, a
      congenital anomaly well documented in humans and foals but not previously
      reported in cattle.

PMID- 15943122
TI  - A clinical trial to assess the use of sodium hypochlorite and oxytetracycline on
      the healing of digital dermatitis lesions in cattle.
AB  - The increased frequency of diseases, especially those of the hoof, cause economic
      losses, such as premature culling of affected animals, decreased milk production,
      weight loss, reduced fertility, and the high costs of treatment. A great variety
      of hoof conditions may affect cattle, one of them is digital dermatitis. These
      conditions are probably due to multiple factorial diseases and present with
      similar clinical signs. Bovine lameness is typically treated by foot trimming and
      debridment of the lesions, coupled when necessary with systemic antibiotics and
      therapeutic footbaths, which results in a clinical cure in the majority of the
      cases. The objective of this study was to evaluate the topical action of sodium
      hypochlorite associated with the systemic use of oxytetracycline for the
      treatment of wounds clinically diagnosed as bovine digital dermatitis. One
      hundred and twenty Holstein cattle varying ages from 1 to 9 y and presenting the
      clinical signs of digital dermatitis, were used in this study. Group 1 (G1)
      received topical treatment with a 1% sodium hypochlorite footbath twice a day for
      30 d and 4 treatments of parenteral oxytetracycline (10 mg/kg bodyweight, IM,
      q48h). Group 2 (G2) received only the topical treatment with 1% sodium
      hypochlorite, as described for G1. Group 3 (G3) received only with parenteral
      oxytetracycline, as described for G1. Group 4 (G4) was treated exclusively with a
      dicloro divynil pirrolidona, ortoiododimetil, para-nitofenil-fosforotioato in a
      vegetal tar-based ointment, immediately after the surgery. After 45 d, the
      recovery rates were as follows: G1, 86.67%; G2, 73.33%; G3, 56.67%; and G4, 50%.
      The surgical treatment of digital dermatitis with subsequent treatment with
      oxytetracycline systemically and 1% sodium hypochlorite topically was the most
      effective for the convalescence of cattle bearing wounds similar to digital
      dermatitis.

PMID- 15943123
TI  - Prevalence of Cryptosporidium parvum infection in southwestern Ontario and its
      association with diarrhea in neonatal dairy calves.
AB  - Cryptosporidium parvum infection was detected in 203 (40.6%) of 500 Ontario dairy
      calves aged 7 to 21 d, on a convenience sample of 51 farms with a history of calf
      diarrhea. Within-farm prevalence ranged from 0% to 70%, and both shedding and
      intensity of shedding were significantly associated with diarrhea. This parasite
      appears to be common in Ontario dairy calves and important as a cause of dairy
      calf scours in the province.

PMID- 15943124
TI  - Medical management of a patent ductus venosus in a dog.
AB  - A 2.5-year-old dog with signs of weight loss, vomiting, and hepatic
      encephalopathy was diagnosed with a patent ductus venosus, based on serum
      biochemical analysis, jejunal portography, and biopsies, and treated with
      lactulose, antibiotics, and a reduced protein diet. Two years after initial
      presentation, the dog is still being managed medically.

PMID- 15943125
TI  - Tissue harvesting for cloning: an ethical perspective for veterinarians.

PMID- 15943126
TI  - The art of terminal illness and injury: the client and the animal.

PMID- 15943127
TI  - Coxofemoral luxations part 1: diagnosis and closed reduction.

PMID- 15943128
TI  - The Institute of Medicine report on complementary and alternative medicine in the
      United States--personal reflections on its content and implications.

PMID- 15943129
TI  - Quality in healthcare: asking the right questions. The next ten years: the role
      of CAM in the "quality cure".

PMID- 15943130
TI  - Quantification of the scientific research in the United States about popular
      herbal remedies referenced on PubMed.
AB  - Herbal supplements are among the most popular complementary and alternative
      therapies used in the US, yet many healthcare providers report having inadequate
      knowledge about herbs. It also has been reported that many healthcare providers
      want to have a better understanding of herbs so that they may recommend or
      discourage their use. In this report, we attempt to determine whether a
      significant body of research has been indexed in PubMed on the most widely used
      herbs in the US. These data also prove useful in determining whether the
      scientific community in the US is focusing investigations on herbs that are
      widely used domestically. In addition, many clinicians in the US use data from
      clinical trials performed in the US to inform their practice, so we wanted to
      determine whether significant clinical data on these herbs were available.

PMID- 15943131
TI  - Advancing acupuncture research.
AB  - Since the early 1970s, acupuncture has been the subject of multiple animal
      experiments and randomized clinical trials. Our understanding of acupuncture from
      both the clinical and mechanistic perspectives has, as a result, grown
      tremendously. Yet the final word on acupuncture as a therapy remains mixed,
      largely due to the contradictory nature of the evidence. With some exception,
      what clinical conditions would benefit and how acupuncture physiologically
      operates remains unclear. The impediment to progress is found in three
      disjunctions in acupuncture research: (1) the biomedical need to standardize
      treatments creates uncertainty about whether we are studying acupuncture
      appropriately; (2) the variability in acupuncture styles creates ambiguity about
      whether we are studying the right style; and (3) the discrepancy between animal
      and human studies creates questions about whether we truly understand the
      underlying mechanism responsible for acupuncture's therapeutic effect. We propose
      that these disjunctions are best addressed with the use of "manualized" protocols
      in clinical trials that are linked with mechanistic studies. Through this
      approach, we can create a healthy dialogue between the medical and acupuncture
      communities and recognize the unique physiologic properties that may be found in
      each acupuncture style. To illustrate how this proposal may fundamentally change
      acupuncture research, we present diabetic neuropathy as a particularly
      interesting model because of its complex heterogeneous pathophysiology.

PMID- 15943132
TI  - Jon Kabat-Zinn, PhD. Bringing mindfulness to medicine. Interview by Karolyn A.
      Gazella.

PMID- 15943133
TI  - Case study: The effectiveness of a dietary supplement regimen in reducing IgG
      mediated food sensitivity in ADHD.

PMID- 15943134
TI  - The significance of enrollment, attendance, and engagement.

PMID- 15943135
TI  - More than just being there: balancing the participation equation.
AB  - The research and evaluation evidence is mounting: out-of-school-time (OST)
      programs can keep young people safe, support working families, and improve
      academic achievement and social development. Over 6 million children are enrolled
      in after-school programs nationwide, but an estimated 14.3 million children still
      care for themselves in the nonschool hours. Because of this discrepancy, OST
      stakeholders need information about how to maximize participation in OST
      programs. The Harvard Family Research Project (HRFP) has developed a conceptual
      model, based on scholarly theory, empirical research, and knowledge gained from
      providers, that describes the characteristics that predict participation in OST
      programs as well as the potential benefits of that participation. In the center
      of the model, participation is conceived as a three-part construct of enrollment,
      attendance, and engagement. This equation serves as the basis for framing this
      issue of New Directions for Youth Development. The chapter provides an overview
      of why participation in OST programs matters for young people, describes some of
      the barriers and challenges to youth participation, teases out more precise
      definitions of participation, and presents HFRP's conceptual model of
      participation. It focuses on the participation equation and concludes by
      highlighting some overarching themes that recur throughout the issue and that
      have an impact on future directions for research and evaluation.

PMID- 15943136
TI  - To participate or not to participate: that is the question.
AB  - Do I wish to participate or not to participate in this program? That is the
      question that young people ask themselves when considering a new opportunity.
      What can be done to increase the likelihood that they will choose to participate
      in out-of-school-time (OST) programs? This chapter describes a qualitative study
      that examined reasons for participating or not participating in OST programs.
      Some common reasons emerged, but the study also revealed differences among youth
      from different ethnic groups. It is clear that those who design and conduct
      programs must understand the processes through which diverse adolescents initiate
      their participation in programs and either persist or drop out. Given the
      apparent benefits of active participation in youth programs, it is important to
      remove barriers and increase access and, equally important, design programs that
      are of interest to youth in the contexts in which they live.

PMID- 15943137
TI  - Recruitment and retention strategies for out-of-school-time programs.
AB  - Many out-of-school-time (OST) practitioners seek ways to maximize enrollment,
      enhance frequency of participation, and ensure retention in OST programs, so that
      the multiple potential benefits of these programs are realized. Three critical
      areas of program quality are important underpinnings for success in recruitment
      and retention of youth in OST programs: a sense of safety and community;
      committed program staff; and challenging, age-appropriate, and fun activities. In
      addition, a review of over sixty OST evaluations reveals five promising
      recruitment strategies to boost enrollment: (1) matching the program to
      participants' needs (offering activities not readily available elsewhere or
      offering flexible schedules), (2) demonstrating the importance of participation
      to young people and their families, (3) reaching out directly to youth and their
      families in their homes and communities, (4) recruiting in peer circles, and (5)
      making a special effort to recruit at-risk youth. Finally, the evaluation
      literature points to five promising strategies to enhance regular participation
      and longterm program retention: (1) sending a clear message that regular
      attendance is important; (2) setting realistic goals to promote regular
      attendance, especially as youth grow older; (3) finding a balance among academic
      and other activities; (4) using incentives; and (5) keeping teens involved with
      opportunities for leadership, community service, and paid employment.

PMID- 15943138
TI  - Present and accounted for: measuring attendance in out-of-school-time programs.
AB  - Evidence is emerging that youth who attend out-of-school-time (OST) programs more
      frequently and for longer periods of time benefit more than youth who attend less
      frequently or do not attend at all. It is also increasingly clear that children
      and youth will not reap the benefits of programs if they do not attend regularly.
      Collecting attendance data can help program leaders gauge demand for services,
      plan and manage programs effectively, and evaluate participant outcomes in
      relation to attendance. This chapter presents these and other reasons for
      collecting attendance data, as well as the methods and techniques that program
      leaders and researchers have at their disposal for measuring attendance. It
      describes four indicators of attendance--absolute attendance, intensity,
      duration, and breadth--that can provide detailed information and insight about
      youth participants and their use of programs. The chapter also provides tips for
      collecting attendance data and features examples from OST programs. Throughout,
      the chapter illustrates that the right indicators and data collection methods
      depend on program needs, characteristics, and goals.

PMID- 15943139
TI  - The ABCs of engagement in out-of-school-time programs.
AB  - The rapid growth of out-of-school time programs over the past five years has
      resulted in a dramatic increase in opportunities for young people. However, many
      programs have been ill defined, without appropriate attention to the
      developmental needs of children and adolescents and without the necessary
      elements in place to fully capture the interests and talents of youth. In this
      chapter, the author shows how constructs drawn from research in education can be
      applied to research and practice in the out-of-school-time arena, in an effort to
      learn how the field can more fully engage young people in activities and
      programs. With more and more research indicating positive connections between
      participation in safe, supportive, and challenging activity settings and healthy
      psychological and social adjustment, attempts to encourage engagement rather than
      casual participation are warranted. Researchers and practitioners need to be
      mindful that engagement results not just from showing up, but from the interplay
      of the affective, behavioral, and cognitive experiences of youth in these
      settings. Suggestions for designing growth-enhancing contexts that increase the
      likelihood of engagement are offered, as are suggestions for future research in
      this area.

PMID- 15943141
TI  - A challenge to church leaders: the necessity of supervision for ordained
      ministers.
AB  - This article is an explicit challenge to church leaders and ministers of all
      denominations to take seriously the necessity of obligatory supervision for
      ordained ministers. To support this challenge, the author describes fundamental
      principles of pastoral care that found the moral demand for and benefits of the
      supervision of pastoral practice. Before offering practical suggestions on the
      implementation of supervision, reasons for the personal and institutional
      resistance to supervision of ordained ministers are depicted.

PMID- 15943140
TI  - Activities, engagement, and emotion in after-school programs (and elsewhere).
AB  - Experiences that are deeply engaging and enjoyable, engender full concentration,
      and present a balance between challenge and skill promote children's development.
      This chapter describes a study that sought to identify the kinds of settings and
      activities that foster engagement and, by extension, positive youth development.
      The after-school experiences of 191 ethnically diverse youth living in three
      states, some of whom participated in after-school programs and some of whom did
      not, were studied. Youth were equipped with logbooks and watches that were
      programmed to signal at random times. When signaled, youth recorded their
      location, social partners, activity, and feelings. The study found pervasive
      differences in the experiences at programs and elsewhere. Youth spent more time
      in academic and arts enrichment, organized sports and physical activities,
      community service, and homework at programs versus elsewhere, and they spent less
      time eating and watching TV at programs. They also reported higher levels of
      motivation, engagement, and positive affect at programs. At the same time, there
      were few differences in activities, emotions, effort, or motivation of program
      participants and nonparticipants when both groups were elsewhere. The
      similarities in these experiences while elsewhere suggest that the program
      context, not differences in youth characteristics or interests, was responsible
      for the feelings of engagement that were reported at programs.

PMID- 15943142
TI  - Existential, theological, and psychological concepts of death: a personal
      retrospective.
AB  - Before Freud, the study of death belonged strictly in the contexts of religion
      and philosophy, but in the 20th Century, death and dying began to enter into
      dialogue with the social sciences of psychology and sociology. The
      existentialists began to portray death differently in their literary-based
      philosophy, and by the end of the century four major American writers had dealt
      squarely with death in a theological framework. The author's own personal
      experiences and academic endeavors frame this evolution in theories about death
      and dying, beginning with a Master's thesis in college and ending with a unit of
      Clinical Pastoral Education in a shock trauma hospital. In this article the
      mystery of death is examined from three distinct points of view: literary
      (including existentialism, a philosophy as literature), theological and
      psychological, based upon the author's career as a professor of literature, as
      seminary student, and as a recent participant in Clinical Pastoral Education. An
      attempt at a synthesis of these three strands of inquiry is made at the end of
      this personal and academic journey.

PMID- 15943143
TI  - Through the looking glass: women and ministry supervision.
AB  - Issues pertaining to women and clinical pastoral supervision are identified and
      examined in this essay. An in-depth literature review regarding the relationship
      between gender and supervised pastoral training provides the basis for the
      identification of the following themes: the relative lack of female supervisors;
      how and why we ought to talk about gender and ministry supervision; the
      contextual relevance of systemic marginalization to ministry supervision; the
      relationship between pastoral care and the "feminine"; the relevance of a
      panentheistic God to gender and ministry supervision; and, lastly, the relevance
      of gender to the supervisory relationship. Although the focus is on the ways in
      which gender dynamics can affect the female supervisee's experience, the author
      also takes a brief look at how female supervisors might experience the relevance
      of their gender to the art of supervision.

PMID- 15943144
TI  - Communication strategies to promote spiritual well-being among people with
      dementia.
AB  - Declining communication skills in dementia threaten a person's sense of self.
      Building on enduring capabilities, pastoral visitors can significantly enhance
      spiritual well-being through the use of individualized, person-centered
      strategies. This article outlines the primary spiritual needs of older adults
      with dementia and some general strategies to improve communication based on
      enduring abilities. Detailed examples illustrate how these personhood-centered
      strategies can meet spiritual needs by connecting with individuals with dementia
      through life stories and through helping them to participate in religious life.

PMID- 15943145
TI  - Developing a Buddhist approach to pastoral care: a peacemaker's view.
AB  - As the United States becomes a more multicultural and multireligious society, the
      ranks of healthcare chaplains are no longer being limited solely to Judeo
      Christian clerics. In an effort to increase interfaith understanding and
      ecumenical awareness, the author presents one model of healthcare chaplaincy that
      derives itself from a Buddhist perspective and how he uses it in his daily work
      at a large medical center in the United States.

PMID- 15943146
TI  - A fairy tale with a twist: pastoral counseling with adoptive families.
AB  - Adoption counseling often focuses primarily on the enigmatic issues faced by
      adoptees. Very little attention, however, is pointed in the direction of the
      adoptive parents and their unique struggles. This article begins by providing
      some current information on adoption in the United States and ensuing
      implications for pastoral caregiving. Some of the unique challenges associated
      with the adoption experience are delineated, primarily focusing on systemic and
      personal issues faced by many adoptive families. Several practical interventions
      are suggested for pastoral caregivers working with adoptive families. Finally,
      the entire adoption experience is framed within a theological perspective
      offering hope to adoptive parents and adoptees.

PMID- 15943147
TI  - Clergy dissatisfaction: denominational hierarchy as a salient factor.
AB  - The author contends that there is a perceived lack of support from denominational
      hierarchy, and that the impact of this lack on clergy has been overlooked in the
      literature. The factor is important because it will underpin the success of any
      strategies attempted to address the cited stressors. As well, no treatment
      strategy for those who struggle with these issues has been defined which seems to
      ignore that this unique population requires unique considerations.

PMID- 15943148
TI  - A national survey of health care administrators' views on the importance of
      various chaplain roles.
AB  - A random sample of hospital administrators throughout the United States was
      surveyed about their views on the importance of eleven chaplain roles and
      functions. The 494 respondents fell into three categories: (1) directors of
      pastoral care departments (N = 132); (2) administrators of hospitals that have a
      pastoral care department (N = 180); and (3) administrators of hospitals that do
      not have a pastoral care department (N = 182). All three groups considered all
      eleven roles to be relatively important, although administrators of hospitals
      that do not have a pastoral care department gave lower ratings, overall. Meeting
      the emotional needs of patients and relatives were seen as chaplains most
      important roles, whereas performing religious rituals and conducting religious
      services were seen as least important by all three groups. In all but a few
      instances, the level of importance that administrators assigned to the various
      roles were positively related to their ratings of their own religiousness and
      spirituality (r's = .11 to .26, p < .05).

PMID- 15943149
TI  - Not well known, used little and needed: Canadian chaplains' experiences of
      published spiritual assessment tools.
AB  - What are Canadian chaplains' experiences of published assessment tools? Utilizing
      a quantitative and qualitative methodology with multiple investigators and
      theoretical triangulation, this article reports the results of a survey of
      chaplains in the Canadian Association for Pastoral Practice and Education (CAPPE)
      and interview results of 15 chaplains in three focus groups. Findings indicated
      that published spiritual assessment tools are not well know, used little,
      criticized for being reductionistic and not fitting the clinical situation.
      Participants noted, however, that spiritual assessment is needed for spiritual
      care. Thirty percent reported the development of their own tools (not published)
      and three published tools were mentioned by 50% and more. Discussion, limitations
      of the research, and suggestions for education, practice, and future research are
      offered.

PMID- 15943151
TI  - A certain tension in clinical pastoral education (CPE) laudable.

PMID- 15943150
TI  - Theological reflections on violence and abuse.
AB  - This article examines the contemporary problem of intimate violence and sexual
      assault within a larger theoretical and theological context. It does so by
      tracing two trajectories in theological thinking: first, that suffering is sent
      from God and requires obedience; and, second, that the roles of men and women are
      not only specific and hierarchical but must remain so lest society risk moral
      chaos. It argues that many messages from traditional Christian theology continue
      to haunt abused women in such a way as to at times facilitate domestic violence.
      It offers suggestions for transforming common theological interpretations in ways
      that are empowering for battered women. These recommendations include attempts to
      emphasize resources within a tradition that may help transform unjust power
      relations like those in abusive relationships.

PMID- 15943152
TI  - Where's the "me"?: reflecting on consciousness in light of brain imaging
      technology.

PMID- 15943153
TI  - God's hospitality: going up!

PMID- 15943154
TI  - An unscientific postscript regarding retirement.

PMID- 15943155
TI  - A good poop.

PMID- 15943156
TI  - Shed your sandals.

PMID- 15943157
TI  - Damascus Hospital: a view from the other side.

PMID- 15943158
TI  - Death through the lens of birth.

PMID- 15943159
TI  - Resurrected silent stirrings.

PMID- 15943160
TI  - Extraventricular neurocytoma presenting with intratumoral hemorrhage.
AB  - A case of extraventricular neurocytoma with spontaneous intratumoral hemorrhage
      is reported. A 47-year-old man presented with sudden left-sided hemiparesis.
      Magnetic resonance imaging revealed a right parietal subcortical mass with
      intratumoral hemorrhagic transformation and without contact to the ventricular
      system. After complete microsurgical removal, the tumor was histologically
      diagnosed as neurocytoma. Usually, the term "central neurocytoma" is restricted
      to neurocytic neoplasms arising within the cerebral ventricles. In the majority
      of the cases, these slow-growing, generally circumscribed lesions become
      symptomatic by obstructive hydrocephalus. Hemorrhagic onset is sporadically
      reported in the literature. In contrast to central neurocytomas, neurocytic
      lesions located within the brain parenchyma, so-called "extraventricular
      neurocytomas" are very uncommon. To the knowledge of the authors, this is the
      first case of an extraventricular neurocytoma with histological classic features
      presenting with intratumoral hemorrhage in adults.

PMID- 15943161
TI  - Primary cerebral toxoplasmosis: a rare case of ventriculitis and hydrocephalus in
      AIDS.
AB  - We describe the clinical, radiological and neuropathological findings in an adult
      AIDS patient presenting with ventriculitis and hydrocephalus as the primary
      manifestations of cerebral toxoplasmosis. Clinical symptoms including fever,
      headache, changes in mental status and focal neurological deficits were non
      specific. Cranial computed tomography showed a subtile ventricular dilatation
      whereas magnetic resonance imaging disclosed triventricular hydrocephalus due to
      stenosis of the aqueduct and a periventricular nodular rim of high signal
      intensity on T2- and proton density-weighted images. This rim also showed a
      slight enhancement on post-contrast T1-weighted images. Focal intracerebral
      lesions could not be delineated, neither by neuroimaging nor by pathology.
      Neuropathological examination showed severe ventriculitis with large ependymal
      and subependymal necrosis as well as dilatation of the lateral and the third
      ventricle. The only microorganism demonstrated at histology in the central
      nervous system was Toxoplasma gondii. We conclude that ventriculitis and
      hydrocephalus without any focal parenchymal lesion may be the only manifestations
      of CNS toxoplasmosis. It is important to recognize this unusual form of
      presentation of cerebral toxoplasmosis in order to perform specific therapy.

PMID- 15943162
TI  - Isolated Rosai Dorfman disease of the central nervous system presenting as dural
      based and intraparenchymal lesions.
AB  - OBJECTIVE: To report three patients with isolated Rosai Dorfman disease of the
      central nervous system. CASE REPORTS: We report two patients with dural-based
      lesions diagnosed imageologically as meningiomas, and one patient with multiple
      intraparenchymal lesions diagnosed imageologically as lymphoma. Two patients were
      males and one was female. All were above 35 years of age with no nodal or other
      system involvement. The diagnosis was established on surgically excised masses
      during histopathology. One patient died due to unrelated causes 10 years later
      and the other two are symptom-free at 21.5- and 11.5-year-follow-up. CONCLUSIONS:
      Awareness of the entity and consideration in the differential diagnosis of dural
      based/intraparenchymal lesions is necessary for diagnosis and prognosis.

PMID- 15943163
TI  - Primary AL (kappa-light chain) amyloidosis manifesting as peripheral neuropathy
      in a young male without increase in serum and urine immunoglobulin load: a
      diagnostic challenge.
AB  - Primary systemic or AL amyloidosis is a multisystem disorder characterized by
      diffuse extracellular infiltration of a fibrillar protein of monoclonal light
      chain origin (AL). Majority of the patients have monoclonal immunoglobulin in
      serum and/or urine and some have clonal proliferation of plasma cells in their
      bone marrow. This disease has the widest spectrum of organ involvement, most
      commonly affecting the kidneys, heart and liver. Involvement of peripheral
      nervous system is not infrequent and may be the presenting feature of the disease
      process. Thus, recognition of peripheral neuropathy and affecting the kidney as
      an early symptom of AL amyloidosis may widen the scope for therapeutic
      intervention. We describe here a rare case of primary amyloidosis (AL) kappa
      light chain presenting with clinical features of peripheral neuropathy and
      affecting the kidney and heart at an early age of 18 years, hitherto unreported
      in literature. The case was further interesting as it was not associated with
      increased serum/urine immunoglobulins or plasma cells in bone marrow. Diagnosis
      was confirmed using immuno-electron microscopy on sural nerve biopsy.

PMID- 15943164
TI  - Polysaccharide storage myopathy--case report and literature review.
AB  - Polysaccharide myopathy is a rare form of storage muscular disorder. The clinical
      picture of this particular form of myopathy is unspecific. We report a 62-year
      old woman with late-onset progressive weakness and wasting, affecting proximal
      muscles of the four limbs and the girdles. No myalgia, dysphagia nor symptoms of
      cardiac failure were observed. Muscle biopsy revealed a vacuolar myopathy with
      accumulation of amylopectin-like polysaccharide. This material was strongly PAS
      positive and diastase-resistant. At electron microscopy, the deposits were
      composed of non-membrane-bound filamentous and granular material surrounded by
      numerous mitochondria. No enzyme deficiency was found. Clinical presentation of
      our patient was similar to the 16 cases reported in the literature. She did not
      have myocardiopathy and her survival is much longer. Hypothetic mechanisms of
      polysaccharide accumulation are reviewed.

PMID- 15943165
TI  - Smoking and weight control behaviors.
AB  - OBJECTIVE: To examine the association between weight control and tobacco use in
      young women. METHODS: Smoking status and weight and eating related issues,
      endorsement of the belief "smoking helps to control weight" dieting status (DEBQ
      R), current and ideal weight and current height were assessed in 144 students.
      RESULTS: Smoker (S) restrained eaters (RE) scored higher on dietary restraint
      than nonsmoker (NS) RE. In the smoking questionnaire, S-RE selected a
      significantly higher number of items concerning hunger, eating and weight than S
      unrestrained eaters (URE). S-RE had a greater level of endorsement of the belief:
      "smoking helps to control weight" than NS-URE. The subjects who marked those
      items had significantly higher scores in the DEBQ-R and were more likely to be RE
      than those who marked none of them. CONCLUSION: Our findings suggest that among
      young women who smoke and diet there might be a risk group that smokes as a
      weight control strategy.

PMID- 15943166
TI  - The relationship between binge eating disorder and non-purging bulimia nervosa.
AB  - AIMS: To further investigate the differentiation between non-purging bulimia
      nervosa (BN-NP) and binge eating disorder (BED), particularly as concerns weight
      shape overconcern affecting self-esteem, a core belief to both anorexia and
      bulimia nervosa. METHODS: Twenty-five female subjects with BN-NP and 25 female
      subjects with BED, consecutively referred to the Eating Disorder Unit of the
      DPPhNB, were administered the BEDCI, the EDI-2 and the BUT. RESULTS: BED patients
      had a higher BMI (35.5 vs. 23.8 kg/m2, p<0.0001) and were slightly older than BN
      NP ones. Weight-shape concerns as one of the main/the most important things
      influencing self-esteem were reported by 68% of BN-NP patients and 62.5% of BED
      ones. Age at onset of binge-eating, weight-cycling, overall impairment due to the
      eating behavior, sexual harassment, depressive and substance abuse comorbidity
      were equally represented in the two groups of patients. BN-NP patients scored
      higher than BED ones as regards EDI drive for thinness (p<0.05) and BUT weight
      phobia (p<0.05), with these scores significantly related to differences in BMI
      (p<0.0005 and p=0.012). Weight-shape overconcern influencing self-esteem was
      predictive of an earlier onset of binge-eating (p<0.05) and higher scores at the
      BUT weight phobia, and body image concerns (p<0.05). CONCLUSIONS: Differences
      between BED and BN-NP seem to be more of degree than type and there seems little
      value in the separation between BED and BN-NP based on weight-shape concerns that
      substantially impair self-esteem. This construct seems core to both disorders and
      plays a substantial role in triggering and maintaining the binge-eating cycle.

PMID- 15943167
TI  - The effect of limited overfeeding during growth on muscle characteristics: a pig
      model.
AB  - Energy restriction affects the hypothalamus, leading to a decrease in production
      of reproductive and thyroid hormones. A decrease in reproductive hormones affects
      fertility and a decrease in thyroid hormones affects muscle metabolism. A pig
      model has been used to determine that reproductive function is negatively
      affected if the normal practice of overfeeding is limited during the late luteal
      phase of the estrous cycle. We used a sub-set of pigs from this study to examine
      effects of limiting overfeeding on thyroid hormones and skeletal muscle (i.e.
      maximal enzyme activities, and muscle fibre characteristics). Eighteen rapidly
      growing gilts were randomized into three groups: 1) feeding a high plane of
      nutrition throughout the first 15 days of the estrous cycle; 2) limited
      overfeeding (25% below the first group) for first 7 days of the estrous cycle
      (early luteal phase), followed by a high plane of nutrition for days 8-15 (late
      luteal phase); and 3) high plane of nutrition throughout the first 7 days of the
      estrous cycle, followed by 8 days of limited overfeeding. Muscle biopsies were
      collected from the triceps brachii, and blood samples were collected for
      assessment of thyroid hormones at days 0 (baseline), 8 and 16. There was no
      effect of limited overfeeding on thyroid hormones, maximal enzyme activities,
      muscle fibre area or muscle fibre type. Limited overfeeding in rapidly growing
      pigs does not affect thyroid hormone status or muscle characteristics.

PMID- 15943168
TI  - Relationship between body weight, quality of life and cardiovascular risk
      factors: a general population based Italian experience.
AB  - BACKGROUND: Within the framework of the Progetto Faenza, the aim of this study
      was to evaluate the effect of cardiovascular risk factors (CVRF) on the health
      related Quality of Life (H-rQoL) of a cohort of patients in the province of
      Ravenna, on the basis of body mass index (BMI). METHODS: The following data were
      collected for each subject: age, sex, weight, height, glycemia, cholesterol
      (total, HDL and LDL), creatinine, uricemia, systolic arterial pressure (SAP) and
      diastolic arterial pressure (DAP), presence/absence of previous CV disorders,
      arterial hypertension, diabetes, antihypertensive therapy, smoking habits and
      physical exercise. To evaluate the H-rQoL the SF-36 general health survey
      questionnaire was used, filled in by the patient at the first examination. To
      test the significance of the differences between the groups (divided by classes
      of Body Mass Index) as regards the metabolic indicators, a univariate analysis of
      variance was performed; on the other hand, to assess which factors affect H-rQoL
      a multivariate analysis was carried out, considering p<0.05 as significant. The
      results are expressed as +/- 1SD. RESULTS: Of the 1108 subjects enrolled in the
      study, 343 subjects (31.2%), including 154 males with a mean age of 44.9 +/- 14.9
      years, filled in the SF-36 questionnaire. A BMI within the normal range
      corresponds to a more satisfactory metabolic (p<0.05) and QoL (p=0.001) picture.
      Age (p<0.001), presence of previous CV disorders (p=0.005), the use of
      antihypertensive drugs (p=0.041) and physical exercise (p=0.002) correlated
      significantly with H-rQoL values. CONCLUSIONS: Health condition and perception
      are significantly affected by a clinical situation characterized by excess
      weight.

PMID- 15943169
TI  - Girls on the Run: improvements in self-esteem, body size satisfaction and eating
      attitudes/behaviors.
AB  - A pilot assessment of a curriculum-based running program geared for girls 8-12
      years old (n=322) was implemented to assess influences regarding psychological
      risk factors leading to disordered eating among girls who participate in sports.
      Utilizing a pretest/posttest study design, researchers administered
      questionnaires in pre-program session T(1), and post-program T(2). Statistical
      tests on self-esteem (t=-10.628, p<0.05), body size satisfaction (t=4.359,
      p<0.05), and eating attitudes/behaviors (t=4.806, p<0.05) revealed statistically
      significant improvements from baseline to post program. A sport-training program
      supplemented with a wellness curriculum may be an effective primary prevention
      program for disordered eating attitudes and behaviors.

PMID- 15943170
TI  - Predictors of eating behaviors in a sample of Mexican women.
AB  - The aim of the study was to develop a model of potential risk factors associated
      to the development of eating behaviors in Mexican women. A structural equation
      model was carried out on a sample of 425 women: high school and college students
      (N=425) with a mean age of 19.1 years (SD=3.8). The variables selected for the
      model were those that obtained significant correlations with the variable "eating
      behaviors": criticism by father/mother, depressed mood, body mass index,
      attitudes and beliefs concerning obesity and dissatisfaction with figure. The
      model fitted the data well, with a non-significant Chi-square. The proportion of
      variance explained for eating behavior by the other variables was 59, the direct
      effects of all the variables were significant, while the total effect of all the
      variables on eating behavior were also significant, particularly the effects of
      the "dissatisfaction with figure" and, "attitudes and beliefs concerning
      obesity". The model yielded similar data to the findings in international
      literature, since they revealed the influence exerted by social pressure on
      thinness, the internalization of the socio-cultural ideal of thinness and the
      role of excess weight in increasing the risk of body dissatisfaction and
      therefore with the development of eating disorders.

PMID- 15943171
TI  - Baseline personality characteristics of responders to 6-month psychotherapy in
      eating disorders: preliminary data.
AB  - OBJECTIVE: The Karolinska Psychodynamic Profile (KAPP) was used for the
      assessment of the six-month outcome of Brief Adlerian Psychodynamic Psychotherapy
      (B-APP). METHOD: Fifty-seven eating disordered women (28 with anorexia nervosa,
      29 with bulimia nervosa), were included in the study. The sample was evaluated at
      baseline (time 0) and after six months (T6) with a clinical assessment and with
      Temperament and Character Inventory (TCI), Eating Disorder Inventory (EDI-2),
      State-Trait Anger Expression Inventory (STAXI), and KAPP. RESULTS: Based on
      symptomatologic improvement, two sub-groups were obtained: responders (66.6%) and
      non-responders (33.3%). Significantly higher baseline scores emerged in the
      responders group on Ineffectiveness and Impulsivity (EDI-2) and on Harm Avoidance
      (TCI). Several KAPP items and areas improved in both groups at T6. CONCLUSION:
      Multimodal treatment centered on B-APP lead to both a global clinical improvement
      and an improvement in several psychological and psychopathological features as
      assessed by EDI-2, STAXI and KAPP. The results suggest interesting clinical
      implications, though outcome predictors are quite weak.

PMID- 15943172
TI  - A short-term cognitive group treatment program gives substantial weight reduction
      up to 18 months from the end of treatment. A randomized controlled trial.
AB  - OBJECTIVE: To describe and evaluate long-term efficacy (18 months from the end of
      treatment) of a new cognitive short-term weight reducing treatment program for
      obese patients. SUBJECTS: One hundred and five obese [Body Mass Index (BMI) > or
      = 30] patients participated in the study. Of these, 62 took part in the treatment
      program and 43 served as controls. METHOD: From an obesity unit's waiting list,
      the patients were randomly assigned to either a treatment group or remained in
      the waiting list to serve as a control group. The treatment group participated in
      a 10-week (30 hours) cognitive group treatment program. All participants were
      weighed at the outset of the study, directly after treatment and at a 6-, 12- and
      18-month post-treatment follow-up without any booster treatment after the 10-week
      program. RESULTS: Fifty-seven (92%) patients completed treatment. For the 34
      (60%) patients who participated in the study 18 months after treatment was
      terminated, the mean weight loss at treatment's end was 8.5 kg (SD=16.1).
      Eighteen months later their mean weight loss was 10.4 kg (SD=10.8). The control
      patients (n=31.72%) that participated in the study during the same period
      increased in weight by 2.3 kg (SD=7.0). The weight difference between the
      treatment and control group at the 18-month follow-up was highly significant
      (p<0.001). CONCLUSION: The cognitive group treatment program was highly
      acceptable among the participants and was completed by nearly all the patients.
      The 10-week treatment program resulted in satisfactory weight loss. The weight
      difference between the treatment group and controls was nearly the same at 18
      months after end of treatment as at six months. The study, therefore, does not
      provide support for the contention that a lengthy therapy for obesity is
      necessary if treatment results are lasting.

PMID- 15943173
TI  - Attitudes towards change and treatment outcome in eating disorders.
AB  - OBJECTIVE: To investigate the influence of the stage of change on treatment
      outcome among patients suffering from eating disorders. METHOD: Sixty-seven women
      receiving free outpatient treatment for eating disorders initially participated
      in this study. Their demographic, lifetime and clinical characteristics, eating
      disorder symptoms and general distress were assesssed at baseline and after one
      year, together with the results of self-report questionnaire on Attitudes towards
      Change in Eating Disorders (ACTA). RESULTS: High scores on the Maintenance
      subscale were protective for eating psychopathology as measured by the Eating
      Attitudes Test (EAT-40), Eating Disorders Inventory (EDI-2) and the frequency of
      purging. Action was predictive of weight changes. Precontemplation and Relapse
      respectively predicted little change in EAT and the Bulimic Inventory Test
      Edinburgh (BITE). High Preparation scores were predictive of the level of EDI-2
      Interoceptive Awareness, Maturity Fears, and Ascetism. DISCUSSION: Our results
      suggest considering the stage of change as a useful outcome predictor.

PMID- 15943174
TI  - Inhibitory effects of cadmium on peripheral blood mononuclear cell proliferation
      and cytokine release are reversed by zinc and selenium salts.
AB  - Zinc (Zn) and selenium (Se) exert regulatory activities on immune functions,
      while cadmium (Cd) is an immunotoxic agent. The object of this study was to
      detect effects of 10(-4), 10(-5), and 10(-6) M Cd sulphate, Zn sulphate, and
      sodium selenite, and their combinations on human peripheral blood mononuclear
      cell (PBMC) proliferation and IFN-gamma and TNF-alpha production. Only 10(-5) M
      Zn sulphate significantly enhanced spontaneous PBMC proliferation, which was
      unaffected by the other salts. At 10(-4) and 10(-5) M, Cd sulphate exerted a dose
      response inhibitory action on phytohemagglutinin- (PHA-) stimulated PBMC
      proliferation and cytokine release, while 10(-4) M and 10(-5) M Zn sulphate and
      10(-5) M sodium selenite induced a stimulatory effect on both proliferation and
      cytokine release; 10(-4) M sodium selenite enhanced only the PBMC proliferation;
      at 10(-6) M, none of the salts changed the PHA-stimulated immune activity.
      Moreover, 10(-4) and 10(-5) M Zn and 10(-5) M Se strongly upregulated IFN-gamma
      (a Th1 cytokine) release, even in presence of 10(-5) M Cd, and reduced the
      inhibitory effects of Cd on PBMC proliferation and TNF-alpha release. This study
      confirms that Zn and Se both strongly enhance cytokine release induced by
      mitogenic stimulation, showing also that Zn acts with a broader range of
      concentrations than Se. This suggests that dietary excess of Se may not have
      beneficial effects.

PMID- 15943175
TI  - Brief communication: morphoproteomic analysis of osteolytic Langerhans cell
      histiocytosis with therapeutic implications.
AB  - Morphoproteomics utilizes immunohistochemistry to identify protein analytes in
      tumor cells in order to uncover or confirm potential molecular pathways that may
      be essential to their proliferation, integrity, and histogenesis and that may
      serve as therapeutic targets. This communication illustrates the application of
      such an approach to osteolytic Langerhans cell histiocytosis and considers such
      molecular targets in the context of currently available therapies.

PMID- 15943176
TI  - In vivo effect of celecoxib and tenoxicam on oxidant/ anti-oxidant status of
      patients with knee osteoarthritis.
AB  - The aim of this study was to compare the in vivo effects on free radical
      metabolism of 2 non-steroidal anti-inflammatory drugs (NSAIDs): tenoxicam, an
      oxicam preferentially cyclooxygenase-1 (COX-1) inhibitor, and celecoxib, a
      sulfonamide selective COX-2 inhibitor. The serum levels of oxidative stress
      related enzymes (ie, xanthine oxidase (XO), superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px)), of a lipid peroxidation marker (malondialdehyde
      (MDA)), and of nitric oxide (NO) in patients with knee osteoarthritis were
      studied at baseline and after a 4-wk course of treatment with celecoxib (n = 11)
      and tenoxicam (n = 12). Celecoxib-treated patients had significant decrease in
      nitrite levels (p = 0.043), whereas SOD, XO, GSH-Px enzyme activities, and MDA
      levels did not change significantly compared to baseline. Tenoxicam-treated
      patients had significant decrease in nitrite levels (p = 0.036) and XO activity
      (p = 0.01), but their SOD, GSH-Px enzyme activities, and MDA levels were
      unchanged from baseline. There was significant correlation between the patients'
      (n = 23) Western Ontario and McMaster Universities (WOMAC) LK3.0 Osteoarthritis
      Index, WOMAC-pain scores, and MDA levels (r = 0.50, p = 0.014) and the patients'
      WOMAC-stiffness scores and XO enzyme activity (r = 0.46, p = 0.027) at baseline.
      Significant improvement was found in pain-VAS, patients' global assessment, and
      WOMAC pain, stiffness, and physical function scores in celecoxib and tenoxicam
      treated groups. In summary, our study revealed that tenoxicam may have
      antioxidant effects, and that celecoxib and tenoxicam may reduce nitrite levels,
      indicating an alteration of NO pathways.

PMID- 15943177
TI  - High incidence of complement C9 deficiency in Koreans.
AB  - Complement 9 deficiency is the most common complement deficiency in Japan, but it
      is rare in western countries. Because of Korea's geographical proximity to Japan,
      C9 deficiency in Korea has also been assumed to be common although this has never
      before been proven. We investigated complement deficiency in the serum samples of
      6,159 Korean hospital outpatients. The deficiency was screened by a sensitive
      hemolytic assay and was confirmed by immunoassay of each complement component.
      Three C9-deficient individuals were found, giving an incidence of 0.049%, which
      is lower than that in Japan but still a considerable figure. Complement
      deficiencies other than that of C9 were not detected in this study. It is
      therefore necessary to consider the possibility of C9 deficiency in the
      interpretation of unexpectedly low complement-mediated hemolytic activity in East
      Asians.

PMID- 15943178
TI  - Microplate ELISA for urine microalbumin: reference values and results in patients
      with type 2 diabetes and cardiovascular disease.
AB  - An ELISA for urine microalbumin using microtiter plates has been developed. The
      assay uses polyclonal anti-human albumin antibody for coating the microtiter
      plates and the same antibody conjugated with horseradish peroxidase for
      detection. The assay sensitivity is 1.6 microg/ml. Results by this in-house ELISA
      show good correlation (r = 0.99) with those obtained by a commercial assay using
      the Behring BNII autoanalyzer. Within-day and between-day CVs are 10%. Reference
      values for microalbumin in 769 urine specimens from healthy Chinese subjects were
      higher in women than men and higher in subjects 50 yr than in those <50 yr of
      age. Elevated mean concentrations of urine microalbumin were observed in patients
      with type 2 diabetes and CVD. This in-house ELISA is simple, sensitive, precise,
      and especially suited for laboratories without expensive autoanalyzers.

PMID- 15943179
TI  - Enzymatic assay of homocysteine on microtiter plates or a TECAN analyzer using
      crude lysate containing recombinant methionine gamma-lyase.
AB  - An enzymatic assay for plasma homocysteine was developed that uses a crude lysate
      of E. coli containing the recombinant enzyme, methionine gamma-lyase. The assay
      uses a commercially available fluorophore and 96-well microtiter plates; it can
      be performed manually or with the TECAN automated analyzer. The CVs for within
      run and between-run precision are < 10%. Close correlation (r > 0.9) was obtained
      between results by this enzymatic method vs a reference HPLC procedure. In a
      Chinese population, the concentration of plasma total homocysteine was found to
      be gender- and age-dependent. Mean concentrations of plasma total homocysteine
      increased with age and were higher in men than women. Serum homocysteine
      concentrations did not differ significantly from those in plasma, provided the
      whole blood specimens were kept at 4 degrees C for 2 hr, or at room temperature
      for < 45 min, between venepuncture and centrifugation.

PMID- 15943180
TI  - Recombinant human erythropoietin pretreatment attenuates myocardial infarct size:
      a possible mechanism involves heat shock Protein 70 and attenuation of nuclear
      factor-kappaB.
AB  - Erythropoietin (EPO), known for its role in stimulating erythropoiesis, has
      recently been shown to have a cardio-protective effect in animal models of
      myocardial ischemia-reperfusion (I-R) injury. The mechanism of the cardio
      protective effect of EPO is unclear. Part of the mechanism for EPO-induced cardio
      protection may involve inhibition of myocardial apoptosis and preservation of ATP
      levels in the ischemic myocardium. We studied the expression of heat shock
      protein 70 (Hsp70) and its possible links to the cardio-protective effect of EPO.
      A rat model of myocardial I-R injury was established by ligating the left
      descending coronary artery for 30 min and then reperfusing for 2 hr. Recombinant
      human EPO (rhEPO) was injected ip 24 hr before the ligation. The myocardial
      infarct size and the area at risk of ischemia were measured by staining with
      triphenyltetrazolium chloride (TTC) and Evans blue dye. Expression of Hsp70 in
      the left ventricle was analyzed by ELISA and that of nuclear factor-kappaB (NF
      kappaB) was analyzed by electrophoretic mobility shift assay (EMSA). The results
      showed that a single ip injection of 3,000 units/kg of rhEPO at 24 hr pre
      ligation enhanced the expression of Hsp70 and diminished the expression of NF
      kappaB in rat myocardium, and that the myocardial infarct induced by I-R injury
      was remarkably reduced in size, compared to control rats that received an ip
      saline injection at 24 hr pre-ligation.

PMID- 15943181
TI  - Brief communication: omega-3 essential fatty acid supplementation and erythrocyte
      oxidant/antioxidant status in rats.
AB  - Fish oil contains large amounts of essential omega-3 fatty acids, such as
      eicosapentaenoic and docosahexaneoic acids, which are building structures of cell
      membranes. The goal of this study was to elucidate the effects of dietary omega-3
      fatty acid supplementation on the oxidant/antioxidant status of erythrocytes in
      rats. The malondialdehyde (MDA) and nitric oxide (NO) levels and the catalase
      (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) activities
      were assayed in erythrocytes of male Wistar albino rats after 30 days of dietary
      supplementation with fish oil (0.4 g/kg/day). Erythrocyte CAT activity in the
      treated group was increased in comparison with the control group. Erythrocyte MDA
      and NO levels were lower in the treated group than the controls. Erythrocyte GSH
      Px and SOD activities did not differ significantly in the 2 groups. Negative
      correlations were found between SOD and CAT activities, and between SOD and GSH
      Px activities in the treated group. In conclusion, omega-3 fatty acid
      supplementation helps to prevent lipid peroxidation and to safeguard erythrocytes
      from oxidative injury. Dietary supplementation with omega-3 fatty acids might
      possibly protect tissues from oxygen free radical injury in the various diseases
      in which the oxidant/antioxidant defense mechanisms are disturbed.

PMID- 15943182
TI  - Mechanism of the effect of hydroxyethyl starch on reducing pulmonary capillary
      permeability in a rat model of sepsis.
AB  - Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes.
      Recent studies have indicated that HES may reduce capillary leakage. The present
      in vivo study was performed to investigate the effects of HES on pulmonary
      capillary permeability, inflammatory mediators, and transcription factors in
      sepsis. Septic rats induced by cecal ligation and puncture (CLP) were treated
      with different doses of HES (7.5, 15, or 30 ml/kg, iv). At 5 or 12 hr after CLPq
      the rat lung tissues were collected. Pulmonary microvascular permeability,
      various cytokine levels (tumor necrosis factor (TNF)-alpha, interleukin (IL)
      1beta, and IL-6), mRNA expressions (cytokine-induced neutrophil chemoattractant
      (CINC), P-selectin, CD 11b/CD18 (Mac-1), and intercellular adhesion molecule-1
      (ICAM-1)), and activities of nuclear factor (NF)-kappaB and activator protein
      (AP)-1 were determined in each group. HES, in a dose-related manner,
      significantly reduced pulmonary capillary permeability in the CLP model of
      sepsis. HES also down-regulated pulmonary proinflammatory cytokines (TNF-alpha,
      IL-1beta, and IL-6) and mRNA expressions (CINC and P-selectin), and inhibited
      pulmonary activities of NF-kappaB and AP-1. The results suggest that during
      sepsis HES reduces pulmonary capillary permeability and this beneficial effect of
      HES may act through down-regulation of inflammatory mediators and suppression of
      NF-kappaB and AP-1 activation.

PMID- 15943183
TI  - Case report: IgM type of membranous glomerulopathy in a diabetic patient.
AB  - We report the case of a 46-yr-old man with a 16-yr history of type I diabetes
      mellitus who developed rapid onset of nephrotic syndrome. Renal biopsy revealed
      diabetic nephropathy, characterized by thickened glomerular basement membranes
      (GBM), mild nodular glomerulosclerosis, and focal arteriolar hyalinization.
      Immunofluorescent (IF) studies showed strong granular IgM staining along
      glomerular loops, with subepithelial and intramembranous immune complex deposits
      along glomerular capillary loops demonstrated by electron microscopy (EM). These
      findings are consistent with membranous glomerulopathy with IgM as the
      predominant immunoglobulin. In addition, there were large aggregates of electron
      dense material composed of numerous ring or spherical particles, ranging from 200
      to 400 nm, in Bowman's space, which corresponded to eosinophilic aggregates on
      light microscopy (LM) and strong IgM stained materials by IF studies.

PMID- 15943184
TI  - Case report and literature review: primary cutaneous carcinosarcoma.
AB  - Carcinosarcomas are rare but aggressive neoplasms commonly described in organs
      such as the breast, urinary bladder, uterus, liver, and lungs.
      Histopathologically, they are characterized by the presence of malignant
      epithelial and mesenchymal components. The exact histogenesis of carcinosarcomas
      remains unknown and is debated in the literature. Primary carcinosarcomas of the
      skin are uncommon. To our knowledge, 20 cases of primary cutaneous carcinosarcoma
      have been described in the world literature. Most of these tumors were seen on
      the head and neck region of older individuals, both male and female.
      Microscopically, the more common carcinoma component is a squamous cell carcinoma
      followed by basal cell carcinoma, whereas the most common sarcoma component is an
      osteosarcoma. We report an example of this rare entity and speculate on its
      histogenesis in the skin.

PMID- 15943185
TI  - Case report: acute promyelocytic leukemia with +der(17)t(15;17) detected by
      fluorescence in situ hybridization (FISH).
AB  - We describe an unusual case of acute promyelocytic leukemia with +der(17)t(15;17)
      as the additional cytogenetic abnormality and with t(15;17) defined by
      fluorescence in situ hybridization (FISH) using a PML/RARA dual color, dual
      fusion translocation probe. By performing a step-by-step, complementary approach
      to evaluate unusual chromosomal abnormalities, we detected RARA/PML fusion on a
      marker chromosome similar to chromosome 17.

PMID- 15943186
TI  - Case report and brief commentary: Wuchereria bancrofti and Onchocerca volvulus co
      infection in a refugee from Sierra Leone.
AB  - Filarial infection is endemic in the tropics and is a public health problem in
      Africa, Asia, South and Central America, and the Pacific Islands. Co-infection
      with filarial nematodes, if unrecognized, can result in untoward therapeutic
      consequences. We report a case of co-infection of Wuchereria bancrofti and
      Onchocerca volvulus that was diagnosed by direct blood smear (W. bancrofti ) and
      serology (O. volvulus) in a native of Sierra Leone. We comment briefly on the
      therapeutic implications of the co-infection.

PMID- 15943187
TI  - A note from history: Rudolph Virchow, pathologist, armed revolutionist,
      politician, and anthropologist.

PMID- 15943188
TI  - A critical strategy: ensuring behavioral health during extended-duration space
      missions.

PMID- 15943189
TI  - Behavioral health: integrating research and application in support of exploration
      missions.
AB  - "Safe Passage: Astronaut Care for Exploration Missions," (Ball JR, Evans CH, eds.
      Washington, DC: National Academy Press; 2001) draws attention to behavioral
      health, an overarching topic that subsumes psychological, interpersonal, and
      cultural adaptation in space. On December 2-3, 2003, the University of
      California, Davis, was the site of a NASA-funded workshop entitled "New
      Directions in Behavioral Health: Integrating Research and Application." The
      purpose of the Workshop was to promote fruitful dialogue between researchers and
      operational personnel in the interests of expanding our understanding of
      behavioral health on Exploration missions including a return to the Moon and a
      voyage to Mars. This paper presents an overview of the rationale and findings of
      that workshop.

PMID- 15943190
TI  - Behavioral health: the propaedeutic requirement.
AB  - Concern about the behavioral effects of spaceflight can be traced back a half
      century to the earliest preparatory bioastronautics experiments in the mid-1
      950s. A central focus of the first primate suborbital flights, as well as the
      orbital chimpanzee pretest flights of Project Mercury, was the effects of such
      stressful ventures on the learned performances of these space behavioral health
      pioneers. The hiatus in spaceflight behavioral health experimental investments
      that followed these early initiatives began with the advent of the 'human
      astronaut' era of the mid-1960s, and has dominated the last several decades.
      Contemporary concerns in this regard have most recently been articulated by a
      turn-of-the-century Committee of the Institute of Medicine, National Academy of
      Sciences, providing a visionary view of space medicine during travel beyond Earth
      orbit. This 2-yr study focused on those most complex behavioral health
      interactions involving humans in extreme, isolated, and confined microsocieties
      areas that have not received the necessary level of attention. The evident
      behavioral health issues raised by the prospect of long-duration exploratory
      missions beyond Earth orbit, including performance and general living conditions,
      recovery and support systems, and the screening, selection, and training of
      candidate participants are reviewed and discussed.

PMID- 15943191
TI  - Human behavioral research in space: quandaries for research subjects and
      researchers.
AB  - With the advent of long-duration spaceflight on board the International Space
      Station (ISS) and possible future missions beyond low Earth orbit (LEO) such as
      Mars, it is critical that those at NASA have a realistic assessment of the
      challenges that will face individuals on long-duration missions so that they can
      develop preventive and real-time countermeasures to behavioral health issues.
      While space travellers are very interested in having countermeasures to the
      deleterious effects of space missions, they have a powerful disincentive to
      participate in this research if they feel it could in any way negatively affect
      their flight status. The behavioral issues of isolation and confinement for
      extended-duration space missions are reviewed. Areas of basic and clinical
      behavioral research are listed. And the classical clinical model for research is
      not considered appropriate for the current configuration of the space program.
      The use of analogue environments and advanced statistical analysis are suggested
      as ways to address the limited spaceflight research opportunities. The challenge
      of research subject or patient confidentiality vs. mission safety and issues of
      personal flight status are addressed.

PMID- 15943192
TI  - Evolution of the Behavioral Sciences Branch of the Space Medicine and Health Care
      Systems Office at the Johnson Space Center.
AB  - This paper presents a brief history of psychology and psychiatry roles in
      psychological selection and how these roles have evolved into the Behavioral
      Sciences Branch at the Johnson Space Center USC), Houston, TX. Since the initial
      selection of the Mercury Seven, the first United States astronauts, psychologists
      and psychiatrists have been involved in astronaut selection activities. Initially
      very involved in psychological selection of astronauts, the role of behavioral
      health specialists waned during the Gemini and Apollo years. With the onset of
      the NASA/Mir/International Space Station Program, the introduction of payload and
      mission specialists, and international collaboration, the evolving need for
      behavioral health expertise became apparent. Medical and psychological selection
      processes were revisited and the Johnson Space Center developed a separate
      operational unit focused on behavioral health and performance. This work unit
      eventually became the Behavioral Sciences branch of the Space Medicine and Health
      Care Systems Office. Research was allocated across groups at JSC, other NASA
      space centers, and the National Space Biomedical Research Institute, and was
      funded by NASA Headquarters. The current NASA focus on human space exploration to
      the Moon and beyond re-emphasizes the importance of the human-centered approach.

PMID- 15943193
TI  - Operational behavioral health and performance resources for international space
      station crews and families.
AB  - The Behavioral Health and Performance Section (BHP) at NASA Johnson Space Center
      provides direct and indirect psychological services to the International Space
      Station (ISS) astronauts and their families. Beginning with the NASA-Mir Program,
      services available to the crews and families have gradually expanded as
      experience is gained in long-duration flight. Enhancements to the overall BHP
      program have been shaped by crewmembers' personal preferences, family requests,
      specific events during the missions, programmatic requirements, and other lessons
      learned. The BHP program focuses its work on four areas: operational psychology,
      behavioral medicine, human-to-system interface, and sleep and circadian. Within
      these areas of focus are psychological and psychiatric screening for astronaut
      selection as well as many resources that are available to the crewmembers,
      families, and other groups such as crew surgeon and various levels of management
      within NASA. Services include: preflight, in flight, and postflight preparation;
      training and support; resources from a Family Support Office; in-flight
      monitoring; clinical care for astronauts and their families; and expertise in the
      workload and work/rest scheduling of crews on the ISS. Each of the four
      operational areas is summarized, as are future directions for the BHP program.

PMID- 15943194
TI  - An operational approach to long-duration mission behavioral health and
      performance factors.
AB  - NASA's participation in nearly 10 yr of long-duration mission (LDM) training and
      flight confirms that these missions remain a difficult challenge for astronauts
      and their medical care providers. The role of the astronaut's crew surgeon is to
      maximize the astronaut's health throughout all phases of the LDM: preflight, in
      flight, and postflight. In support of the crew surgeon, the NASA-Johnson Space
      Center Behavioral Health and Performance Group (JSC-BHPG) has focused on four key
      factors that can reduce the astronaut's behavioral health and performance. These
      factors are defined as: sleep and circadian factors; behavioral health factors;
      psychological adaptation factors; and human-to-system interface (the interface
      between the astronaut and the mission workplace) factors. Both the crew surgeon
      and the JSC-BHPG must earn the crewmember's trust preflight to encourage problem
      identification and problem solving in these four areas. Once on orbit, the crew
      medical officer becomes a valuable extension of the crew surgeon and BHPG on the
      ground due to the crew medical officer's constant interaction with crewmembers
      and preflight training in these four factors. However, the crew surgeon, BHPG,
      and the crew medical officer need tools that will help predict, prevent, monitor,
      and respond to developing problems. Objective data become essential when
      difficult mission termination decisions must be made. The need for behavioral
      health and performance tool development creates an environment rich for
      collaboration between operational healthcare providers and researchers. These
      tools are also a necessary step to safely complete future, more autonomous
      exploration-class space missions.

PMID- 15943195
TI  - Models of research-operational collaboration for behavioral health in space.
AB  - Addressing the behavioral health needs of astronauts clearly requires
      collaborations involving researchers, clinicians and operational support
      personnel, program administrators, and the astronauts themselves. However, such
      collaborations are often compromised by a failure to understand the needs,
      priorities, constraints, and preferences of potential collaborators. This
      failure, in turn, can lead to research of poor quality, implementation of
      programs and procedures that are not evidence-based, and an increased risk of
      morbidity and mission failure. The experiences of social marketing strategies in
      health promotion and disease prevention, cultural exchange between developers of
      evidence-based treatments and consumers, and dissemination and implementation of
      evidence-based practices in mental health services offer three different models
      of research-operational collaboration with relevance to behavioral health in
      space. Central to each of these models are the patterns of interpersonal
      relations and the individual, social, and organizational characteristics that
      influence these patterns. Any program or countermeasure for behavioral health in
      space must be both needs-based and evidence-based. The successful development,
      dissemination, implementation, and sustainability of such a program require
      communication, collaboration, and consensus among all key stakeholders. To
      accomplish this, all stakeholders must participate in creating a culture of
      operational research.

PMID- 15943196
TI  - Invulnerability, coping, salutogenesis, integration: four phases of space
      psychology.
AB  - The relationship between NASA and the psychological research community has
      progressed through a number of phases during the past four decades. This paper
      summarizes how the relationship has developed as data have accumulated and space
      missions and crews have changed. In the beginning, most NASA astronauts and staff
      considered possible psychological problems during space missions to be a non
      issue. It was assumed that people with "the right stuff" would not experience any
      such problems. A more realistic recognition of stress and its consequences has
      led to a concern with prevention and countermeasures, a concern that has come to
      dominate NASA's involvement with psychology. Very recently, space psychologists
      have started to import the concepts of positive psychology, and consider the
      benefits of participation in the space program, including the self-enhancing
      aspects of stressful experiences (salutogenesis). Both the agency and
      psychologists now need to broaden their thinking and their research to cover the
      gamut of empirical data and theoretical concepts. These include human strengths
      as well as vulnerabilities, both negative and positive impacts of spaceflight,
      long- as well as short-term effects, and the reactions not only of the astronauts
      themselves but also of ground personnel and the families of both groups.

PMID- 15943197
TI  - Whole lot of parts: stress in extreme environments.
AB  - Stress has been a central interest for researchers of human behavior in extreme
      and unusual environments and also for those who are responsible for planning and
      carrying out expeditions involving such environments. This paper compares the
      actuarial and case study methods for predicting reactions to stress. Actuarial
      studies are useful, but do not tap enough variables to allow us to predict how a
      specific individual will cope with the rigors of an individual mission. Case
      histories provide a wealth of detail, but few investigators understand the
      challenges of properly applying this method. This study reviews some of the
      strengths and weaknesses of the actuarial and case history methods, and presents
      a four celled taxonomy of stress based on method (actuarial and case history) and
      effects (distress and eustress). For both research and operational purposes, the
      person, the setting, and time should not be considered independently; rather, it
      is an amalgam of these variables that provides the proper basis of analysis.

PMID- 15943198
TI  - Behavioral health in Antarctica: implications for long-duration space missions.
AB  - Ideally, evidence from long-duration spaceflight should be used to predict likely
      occurrences of behavioral health events and for planning management strategies
      for such events. With small numbers of space travelers, and limited long-duration
      missions of a year or more, Earth analogues and simulations must be used as the
      evidence base, despite such analogues lacking microgravity, radiation, rapidly
      altering photoperiodicity, and fidelity to space. Antarctic health data are
      reviewed and an assessment made of the likely frequency of behavioral health
      events. Based on the Antarctic evidence, the likelihood of behavioral health
      problems in space is low. However, such cases may be serious and of high
      consequence, placing considerable demands on the mission crew and ground support
      to achieve a successful outcome, given the availability of pharmaceuticals and
      resources.

PMID- 15943199
TI  - Analogue prototypes for Lunar and Mars exploration.
AB  - Small groups living and working in isolation and confinement experience unique
      stressors that have predictable effects on individual adjustment and performance.
      Because the stress is cumulative, long-duration missions impose considerable
      burdens on an individual's capacity to adjust to the conditions and to perform
      well, both technically and socially. This paper describes research conducted to
      extrapolate design and procedural guidelines for lunar and planetary expeditions
      from a review of information concerning previous expeditions and voyages of
      discovery.

PMID- 15943200
TI  - Men and women in space.
AB  - The influence of gender on the social context in which work performance takes
      place is considered. Women in single and mixed-gender polar expedition groups
      reported concern for the welfare of a teammate as a significant stressor. All
      male teams exhibited higher levels of competitiveness and a lesser tendency to
      talk about their feelings. Excerpts from expedition debriefing interviews
      illustrate gender-related patterns noted in extreme environments. Application of
      these findings for the better selection, training, and performance of mixed
      gender space crews is examined. A case study approach to conducting research on
      crew performance is recommended, and strategies for dealing with confidentiality
      are discussed.

PMID- 15943201
TI  - Life, survival, and behavioral health in small closed communities: 10 years of
      studying isolated Antarctic groups.
AB  - In the late 1980s the Australian Antarctic Division collaborated with NASA to use
      the Australian National Antarctic Research Expeditions' (ANARE) stations to
      pursue research of benefit to both programs. This article outlines the data
      collection efforts, the development of analyses, and selected results, and
      describes some of the benefits for the aerospace, health, and environmental
      psychology communities. The Behavior and Performance Laboratory at Johnson Space
      Center developed a questionnaire to sample broadly the many aspects of life in
      extreme environments analogous to space missions. Data were collected from
      volunteers involved in various ANAREs conducted from 1994 to 2003. Pool-timed
      series regression, hierarchical models, and content analysis have all enhanced
      the understanding of the kinds of psychosocial variables relevant in extreme
      environments, and how these variables relate to each other; examples are given.
      Observations gathered over the last 10 yr comprise a unique, comprehensive, and
      advanced representation of psychosocial factors in this extreme environment and
      provide a strong base for future research and application.

PMID- 15943203
TI  - Enduring the shipboard stressor complex: a systems approach.
AB  - A high incidence of physiological and psychological stressors characterizes the
      maritime work environment in many segments of the commercial maritime industry
      and in the military. Traditionally, crewmembers work embedded in a complex of
      stressors. Stressors rarely act independently because most occur concurrently,
      simultaneously taxing physical and mental resources. Stressors such as extreme
      environmental temperatures, long work hours, heavy mental and physical workload,
      authoritative leadership, isolation from family and loved ones, lack of exercise,
      and unhealthy diets often combine to degrade crewmember health and performance,
      particularly on long voyages. This complex system of interacting stressors
      affects the ability of maritime crewmembers to maintain adequate levels of
      alertness and performance. An analytical systems approach methodology is
      described here as a viable method to identify workplace stressors and track their
      systemic interactions. A systems-based program for managing the stressor complex
      is then offered, together with the empirical research supporting its efficacy.
      Included is an example implementation of a stressor-control program aboard a U.S.
      Coast Guard cutter.

PMID- 15943202
TI  - Circadian rhythms, sleep, and performance in space.
AB  - Maintaining optimal alertness and neurobehavioral functioning during space
      operations is critical to enable the National Aeronautics and Space
      Administration's (NASA's) vision "to extend humanity's reach to the Moon, Mars
      and beyond" to become a reality. Field data have demonstrated that sleep times
      and performance of crewmembers can be compromised by extended duty days,
      irregular work schedules, high workload, and varying environmental factors. This
      paper documents evidence of significant sleep loss and disruption of circadian
      rhythms in astronauts and associated performance decrements during several space
      missions, which demonstrates the need to develop effective countermeasures. Both
      sleep and circadian disruptions have been identified in the Behavioral Health and
      Performance (BH&P) area and the Advanced Human Support Technology (AHST) area of
      NASA's Bioastronautics Critical Path Roadmap. Such disruptions could have serious
      consequences on the effectiveness, health, and safety of astronaut crews, thus
      reducing the safety margin and increasing the chances of an accident or incident.
      These decrements oftentimes can be difficult to detect and counter effectively in
      restrictive operational environments. NASA is focusing research on the
      development of optimal sleep/wake schedules and countermeasure timing and
      application to help mitigate the cumulative effects of sleep and circadian
      disruption and enhance operational performance. Investing research in humans is
      one of NASA's building blocks that will allow for both short- and long-duration
      space missions and help NASA in developing approaches to manage and overcome the
      human limitations of space travel. In addition to reviewing the current state of
      knowledge concerning sleep and circadian disruptions during space operations,
      this paper provides an overview of NASA's broad research goals. Also, NASA-funded
      research, designed to evaluate the relationships between sleep quality, circadian
      rhythm stability, and performance proficiency in both ground-based simulations
      and space mission studies, as described in the 2003 NASA Task Book, will be
      reviewed.

PMID- 15943204
TI  - Long-term personality data collection in support of spaceflight and analogue
      research.
AB  - This is a review of past and present research into personality and performance at
      the University of Texas (UT) Human Factors Research Project. Specifically,
      personality trait data collected from astronauts, pilots, Antarctic personnel,
      and other groups over a 15-yr period is discussed with particular emphasis on
      research in space and space analogue environments. The UT Human Factors Research
      Project conducts studies in personality and group dynamics in aviation, space,
      and medicine. Current studies include personality determinants of professional
      cultures, team effectiveness in both medicine and aviation, and personality
      predictors of long-term astronaut performance. The Project also studies the
      design and effectiveness of behavioral strategies used to minimize error and
      maximize team performance in safety-critical work settings. A multi-year
      personality and performance dataset presents many opportunities for research,
      including long-term and follow-up studies of human performance, analyses of
      trends in recruiting and attrition, and the ability to adapt research design to
      operational changes and methodological advances. Special problems posed by such
      long-duration projects include issues of confidentiality and security, as well as
      practical limitations imposed by current peer-review and short-term funding
      practices. Practical considerations for ongoing dataset management include
      consistency of assessment instruments over time, variations in data acquisition
      from one year to the next, and dealing with changes in theory and practice that
      occur over the life of the project. A fundamental change in how research into
      human performance is funded would be required to ensure the ongoing development
      of such long-duration research databases.

PMID- 15943205
TI  - Interpersonal issues in space: Shuttle/Mir and beyond.
AB  - Anecdotal reports from space and results from space analogue experiments on Earth
      have suggested a number of interpersonal issues that may negatively affect
      crewmember performance and well-being. We examined some of these issues in a
      questionnaire survey of 54 astronauts and cosmonauts who had flown in space and
      in a 135-d Mir Space Station simulation study in Moscow. We also conducted a NASA
      funded study involving missions to the Mir Space Station, where 5 U.S.
      astronauts, 8 Russian cosmonauts, and 42 U.S. and 16 Russian mission control
      subjects completed weekly mood and group climate questionnaires. There were few
      findings that supported hypothesized changes in tension and group behavior in
      terms of time on-orbit. Crewmembers reported decreasing leader support in the
      second half of their mission, and U.S. astronauts gave evidence for a novelty
      effect in the first few weeks. There was strong support for our hypothesized
      displacement of tension and negative emotions from crewmembers to mission control
      personnel and from mission control personnel to management. There were several
      significant differences in response between Americans vs. Russians and
      crewmembers vs. mission control personnel. These findings have training
      countermeasure implications for future on-orbit space missions. During
      expeditionary type space missions, such as a trip to Mars, additional
      interpersonal stressors will need to be dealt with. These include increased crew
      autonomy, more dependence on onboard technical resources, communication delays
      with the Earth, increased isolation and monotony, and the Earth-out-of-view
      phenomenon.

PMID- 15943206
TI  - Cultural factors and the International Space Station.
AB  - The American and Russian/Soviet space programs independently uncovered
      psychosocial risks inherent in long-duration space missions. Now that these two
      countries are working together on the International Space Station (ISS), American
      Russian cultural differences pose an additional set of risk factors. These may
      echo cultural differences that have been observed in the general population of
      the two countries and in space analogue settings, but little is known about how
      relevant these are to the select population of space program personnel. The
      evidence for the existence of mission-relevant cultural differences is reviewed
      and includes cultural values, emotional expressivity, personal space norms, and
      personality characteristics. The review is focused primarily on Russia and the
      United States, but also includes other ISS partner countries. Cultural
      differences among space program personnel may have a wide range of effects.
      Moreover, culture-related strains may increase the probability of distress and
      impairment. Such factors could affect the individual and interpersonal
      functioning of both crewmembers and mission control personnel, whose performance
      is also critical for mission safety and success. Examples from the anecdotal and
      empirical literature are given to illustrate these points. The use of existing
      assessment strategies runs the risk of overlooking important early warning signs
      of behavioral health difficulties. By paying more attention to cultural
      differences and how they might be manifested, we are more likely to detect
      problems early while they are still mild and resolvable.

PMID- 15943207
TI  - Multi-team dynamics and distributed expertise in imission operations.
AB  - The evolution of space exploration has brought an increased awareness of the
      social and socio-technical issues associated with team performance and task
      coordination, both for the onboard astronauts and in mission control. Spaceflight
      operations create a unique environment in which to address classic group dynamics
      topics including communication, group process, knowledge development and sharing,
      and time-critical task performance. Mission operations in the early years of the
      21st century have developed into a set of complex, multi-team task settings
      incorporating multiple mission control teams and flight crews interacting in
      novel ways. These more complex operational settings help highlight the emergence
      of a new paradigm of distributed supervisory coordination, and the need to
      consider multiple dimensions of expertise being supported and exchanged among
      team members. The creation of new mission profiles with very long-duration time
      scales (months, rather than days) for the International Space Station, as well as
      planned exploration missions to the Moon and Mars, emphasize fundamental
      distinctions from the 40 yr from Mercury to the Space Shuttle. Issues in
      distributed expertise and information flow in mission control settings from two
      related perspectives are described. A general conceptual view of knowledge
      sharing and task synchronization is presented within the context of the mission
      control environment. This conceptual presentation is supplemented by analysis of
      quasi-experimental data collected from actual flight controllers at NASA-Johnson
      Space Center, Houston, TX.

PMID- 15943208
TI  - Crew collaboration in space: a naturalistic decision-making perspective.
AB  - Successful long-duration space missions will depend on the ability of crewmembers
      to respond promptly and effectively to unanticipated problems that arise under
      highly stressful conditions. Naturalistic decision making (NDM) exploits the
      knowledge and experience of decision makers in meaningful work domains,
      especially complex sociotechnical systems, including aviation and space. Decision
      making in these ambiguous, dynamic, high-risk environments is a complex task that
      involves defining the nature of the problem and crafting a response to achieve
      one's goals. Goal conflicts, time pressures, and uncertain outcomes may further
      complicate the process. This paper reviews theory and research pertaining to the
      NDM model and traces some of the implications for space crews and other groups
      that perform meaningful work in extreme environments. It concludes with specific
      recommendations for preparing exploration crews to use NDM effectively.

PMID- 15943209
TI  - Behavioral and health implications of civilian spaceflight.
AB  - The current enthusiasm over the prospect of space tourism and the belief among
      many that such civilian spaceflight is imminent are characterized herein. There
      are many concerns about screening and certifying passengers for future
      spaceflight. Efforts by several organizations to propose such screening are
      cited. The problem with some of these proposals, which treat all types of
      spaceflight the same, is that they are so restrictive that too few people would
      be eligible for space travel to have a viable tourism industry. However, not all
      types of spaceflight are the same, so the distinctions between them need to be
      clarified. Of the five types of spaceflight described, one is proposed as the
      most likely to be the first significant phase of space tourism: long-term
      microgravity flight in low Earth orbit. But because of human problems with long
      term exposure to microgravity, this phase requires rather conservative screening
      and extensive training. However, prior to discussing the passenger issues related
      to this early phase of space tourism, the reasons why Earth-like gravity, as well
      as microgravity, must be made available to spacefarers before space tourism can
      take place on a grand scale need to be explained. Finally, major passenger
      medical and behavioral issues of the first phase of orbital space tourism-long
      term microgravity flight-are discussed.

PMID- 15943210
TI  - Optical computer recognition of facial expressions associated with stress induced
      by performance demands.
AB  - Application of computer vision to track changes in human facial expressions
      during long-duration spaceflight may be a useful way to unobtrusively detect the
      presence of stress during critical operations. To develop such an approach, we
      applied optical computer recognition (OCR) algorithms for detecting facial
      changes during performance while people experienced both low- and high-stressor
      performance demands. Workload and social feedback were used to vary performance
      stress in 60 healthy adults (29 men, 31 women; mean age 30 yr). High-stressor
      scenarios involved more difficult performance tasks, negative social feedback,
      and greater time pressure relative to low workload scenarios. Stress reactions
      were tracked using self-report ratings, salivary cortisol, and heart rate.
      Subjects also completed personality, mood, and alexithymia questionnaires. To
      bootstrap development of the OCR algorithm, we had a human observer, blind to
      stressor condition, identify the expressive elements of the face of people
      undergoing high- vs. low-stressor performance. Different sets of videos of
      subjects' faces during performance conditions were used for OCR algorithm
      training. Subjective ratings of stress, task difficulty, effort required,
      frustration, and negative mood were significantly increased during high-stressor
      performance bouts relative to low-stressor bouts (all p < 0.01). The OCR
      algorithm was refined to provide robust 3-d tracking of facial expressions during
      head movement. Movements of eyebrows and asymmetries in the mouth were extracted.
      These parameters are being used in a Hidden Markov model to identify high- and
      low-stressor conditions. Preliminary results suggest that an OCR algorithm using
      mouth and eyebrow regions has the potential to discriminate high- from low
      stressor performance bouts in 75-88% of subjects. The validity of the workload
      paradigm to induce differential levels of stress in facial expressions was
      established. The paradigm also provided the basic stress-related facial
      expressions required to establish a prototypical OCR algorithm to detect such
      changes. Efforts are underway to further improve the OCR algorithm by adding
      facial touching and automating application of the deformable masks and OCR
      algorithms to video footage of the moving faces as a prelude to blind validation
      of the automated approach.

PMID- 15943211
TI  - Development and validation of the spaceflight cognitive assessment tool for
      windows (WinSCAT).
AB  - The Spaceflight Cognitive Assessment Tool for Windows (WinSCAT) was developed by
      an integrated product team as a tool to support medical operations at NASA
      Johnson Space Center and as way to monitor the neurocognitive status of space
      crews. It is based on 20 yr of experience in performance and cognitive testing
      within the U.S. Department of Defense. As a result, WinSCAT development has
      benefited from diverse efforts supporting its technical reliability and
      validation. The rationale, background, and development of WinSCAT are described,
      research supporting its use is summarized, and recommendations are made for its
      continued development.

PMID- 15943212
TI  - The minicog rapid assessment battery: developing a "blood pressure cuff for the
      mind".
AB  - Human exploration of space is a high-risk, high-stress endeavor. Thus, human
      error must be guarded against at every juncture. We have implemented a portable
      system, the MiniCog Rapid Assessment Battery, to assess quickly and accurately
      nine cognitive functions (including attention, working memory, and problem
      solving). This system is intended to provide an "early warning," indicating when
      an astronaut or other type of worker is suffering from stress-related deficits
      that may affect performance. The results can be used to warn a worker to pay
      additional attention or take a countermeasure (even if only a brief rest). At
      present, the MiniCog platform is fully functional; it includes software for
      administering cognitive tests on a hand-held device and providing immediate user
      feedback, as well as desktop software for authoring new tests and scoring results
      in detail. Studies are underway to assess the utility of the MiniCog Rapid
      Assessment Battery for measuring impaired cognitive performance induced by a
      variety of stressors, for evaluating countermeasures, and for predicting
      performance on more complex tasks. We hope that this tool will allow quick and
      easy self-diagnosis of cognitive impairment, encouraging better mental health and
      facilitating safer on-the-job (and recreational) performance.

PMID- 15943213
TI  - Mount Everest: a space analogue for speech monitoring of cognitive deficits and
      stress.
AB  - In deep-space missions, the basal ganglia and hippocampus, subcortical structures
      of the brain that play critical roles in motor activity, cognition, and memory,
      will be vulnerable to damage from cosmic rays. These metabolically active
      structures are also sensitive to damage arising from the low oxygen content of
      air at extreme altitudes. We have, therefore, used Mount Everest as an analogue
      for deep space, where astronauts will be subject to danger and stress as well as
      neural damage. We can ethically obtain data because our climber-subjects already
      intend to climb Mt. Everest. We record speech and test cognitive and linguistic
      performance before, during, and after exposure to hypoxic conditions. From these
      data we have derived and validated computer-implemented acoustic voice measures
      that track slight as well as profound cognitive impairment. Vowel duration and
      speech motor sequencing errors increase as climbers ascend, reflecting degraded
      basal ganglia activity. These metrics detect deficits in language comprehension
      and the ability to change plans in changing circumstances. Preliminary analyses
      also reveal memory deficits reflecting hippocampal damage. Our speech metrics are
      unobtrusive and do not reveal the content of a verbal message; they could be
      derived automatically, allowing space crews to detect subtle motor and cognitive
      deficits and invoke countermeasures before performance is profoundly impaired. In
      future work we will be validating the voice metrics of stress in collaboration
      with the Dinges NSBRI laboratory study of task-induced stress. Our procedures can
      also be applied in general aviation and in the treatment of Parkinson's disease,
      Alzheimer's dementia, and other neurological disorders.

PMID- 15943214
TI  - Cognitive avionics and watching spaceflight crews think: generation-after-next
      research tools in functional neuroimaging.
AB  - Confinement and isolation have always confounded the extraordinary endeavor of
      human spaceflight. Psychosocial health is at the forefront in considering risk
      factors that imperil missions of 1- to 2-yr duration. Current crewmember
      selection metrics restricted to behavioral observation by definition observe
      rather than prevent performance degradation and are thus inadequate when
      preflight training cannot simulate an entire journey. Nascent techniques to
      monitor functional and task-related cortical neural activity show promise and can
      be extended to include whole-brain monitoring. Watching spaceflight crews think
      can reveal the efficiency of training procedures. Moreover, observing subcortical
      emotion centers may provide early detection of developing neuropsychiatric
      disorders. The non-invasive functional neuroimaging modalities
      electroencephalography (EEG), magnetoencephalography (MEG), magnetic resonance
      imaging (MRI), and near-infrared spectroscopy (NIRS), and highlights of how they
      may be engineered for spacecraft are detailed. Preflight and in-flight
      applications to crewmember behavioral health from current generation, next
      generation, and generation-after-next neuroscience research studies are also
      described. The emphasis is on preventing the onset of neuropsychiatric
      dysfunctions, thus reducing the risk of mission failure due to human error.

PMID- 15943215
TI  - An interactive media program for managing psychosocial problems on long-duration
      spaceflights.
AB  - Space crews must be self-reliant to complete long-duration missions successfully.
      This project involves the development and evaluation of a network of self-guided
      interactive multimedia programs to train and assist long-duration flyers in the
      prevention, assessment, and management of psychosocial problems that can arise on
      extended missions. The system is currently under development and is intended for
      use both during training and on orbit. A virtual space station 3-dimensional
      graphic was created to serve as a portal to multimedia-based training,
      assessment, and intervention resources. Additionally, original content on
      interpersonal conflict and depression is being developed for the system. Input on
      the best practices for managing conflict and depression on extended missions was
      obtained from 13 veteran long-duration flyers, as well as from clinical experts.
      Formative evaluation of a prototype of the system will be conducted with 10
      members of the astronaut corps. Subsequently, the content on conflict and
      depression will be completed, and the depression self-treatment portion will be
      evaluated in a randomized controlled trial. Although this study involves
      developing countermeasures to assist long-duration flyers, it also provides a
      model that could be applied in many Earthbound settings, both in operational
      environments and in everyday life.

PMID- 15943216
TI  - Survey of pharmacists' and physicians' perceptions of therapeutic interchange.
AB  - Therapeutic interchange has long been an integral part of drug formulary
      management, but physicians' and pharmacists' attitudes toward such programs are
      relatively unknown. This survey was undertaken to determine pharmacists'
      attitudes, physicians' potential response to a hypothetical interchange, and how
      well pharmacists predicted physicians' responses. A survey that described a drug
      interchange program and several potential responses to the proposed switch was
      provided to 300 staff physicians at a 512-bed community facility in southwest
      Florida; the survey was also mailed to pharmacy directors or clinical pharmacy
      coordinators at 42 southwest Florida hospitals. Responses were obtained from 98
      physicians and 95 pharmacists. Most physicians would not cooperate with an
      interchange if they were not familiar with the proposed drug; 16% would continue
      to prescribe the original drug, knowing that the new agent would be provided; and
      58% would switch to another agent with which they had clinical experience. Only
      26% of physicians would follow the interchange program. In contrast, 48% of
      pharmacists believed that physicians would continue to order the original
      therapy, 32% believed that physicians would order the new agent, and only 20%
      believed that physicians would switch to an alternative drug (P<.005 vs physician
      responses). Clearly, pharmacists' expectations of physicians' response to a
      therapeutic interchange differ significantly from the physicians' expected
      behavior. This difference has potentially important implications for actual
      versus projected cost savings of therapeutic interchange.

PMID- 15943217
TI  - A model of standardized training in basic life support skills of emergency
      medicine residents.
AB  - This intervention study was designed to determine the current level of basic life
      support knowledge and skills of residents in a university-based emergency
      medicine residency program, and to investigate the potential benefit derived by
      these residents from a standardized theoretical and practical training session.
      All residents underwent tests before and after the training session. The
      residents were asked to perform basic life support on a recording cardiopulmonary
      resuscitation mannequin. Assessments were made using a 10-item checklist, with
      the highest score being 17. Each step performed by the resident was scored by an
      emergency physician for accuracy and effectiveness. Twenty-eight residents
      participated in the study. According to the modified Berden scale, the pretest
      and posttest scores were 11.2 +/- 2.9 and 15.6 +/- 1.0, respectively, and the
      mean difference was 4.36 +/- 2.9 (t test, P<.001). Only 11 residents (39.3%) were
      rated as "good" or "very good" in the pretest, whereas the corresponding figure
      in the posttest was 27 (96.4%) (P<.001). Skills, such as checking the airway
      patency (P<.001), checking breathing (P<.001), appropriate compression rate
      (P<.003), and delivering 2 effective breaths (P<.001), improved significantly.
      Depth of chest compression (P<.023) was improved significantly only in residents
      with fewer than 2 years of experience. The training process should comprise
      standardized courses to facilitate acquisition of the desired skills.

PMID- 15943218
TI  - Difficult cardiac situations in renal transplant patients.

PMID- 15943219
TI  - Use of sibutramine, an inhibitor of the reuptake of serotonin and noradrenaline,
      in the treatment of binge eating disorder: a placebo-controlled study.
AB  - Binge-eating disorder, which is characterized by repeated episodes of
      uncontrolled eating, is common in obese patients and is often accompanied by
      comorbid psychiatric disorders, especially depression. In previous studies,
      selective serotonin reuptake inhibitors have demonstrated efficacy in reducing
      the frequency of binge eating and addressing comorbid psychiatric disorders, but
      they have not shown the ability to promote weight loss. Sibutramine, a new
      serotonin and norepinephrine reuptake inhibitor, has been shown in short- and
      long-term studies to be effective in promoting and maintaining weight loss in
      obese patients who have binge-eating disorder. In this randomized, double-blind,
      placebo-controlled study, the efficacy, safety, and tolerability of sibutramine
      were evaluated in the treatment of binge-eating disorder in obese patients.
      Twenty patients were randomly assigned in equal numbers to receive either
      sibutramine 10 mg/day or placebo for 12 weeks. Assessments were made at baseline
      and every 2 weeks throughout the study. Binge frequency, defined as the number of
      days during the previous week that included binge-eating episodes, was the
      primary outcome measure. By the end of the study, the binge frequency among
      patients given sibutramine was significantly lower than that among those given
      placebo. The main adverse events in the sibutramine group were dry mouth and
      constipation. The findings suggest sibutramine is an effective medication in the
      treatment of binge-eating disorders and is well tolerated. In addition, it
      addresses the 3 main goals in the treatment of binge-eating disorder: reducing
      the frequency of binge eating, promoting and maintaining weight loss, and
      treating the comorbid psychiatric conditions.

PMID- 15943220
TI  - Comparative efficacy of valsartan and olmesartan in mild-to-moderate
      hypertension: results of 24-hour ambulatory blood pressure monitoring.
AB  - The aim of this prospective, randomized, open-label, blinded endpoint (PROBE)
      study was to compare the antihypertensive efficacy of 2 angiotensin II (AII)
      receptor antagonists with different pharmacologic profiles, valsartan and
      olmesartan, in patients with mild-to-moderate essential hypertension. After an
      initial 2-week washout period, 114 patients (64 men, 50 women; aged 35-70 years)
      were randomly assigned to receive valsartan 160 mg or olmesartan 20 mg once daily
      for 8 weeks. After the washout period and after 2 and 8 weeks of treatment, 24
      hour ambulatory blood pressure monitoring (ABPM) was performed using a
      noninvasive device, and casual blood pressure (BP) and heart rate were measured.
      Both olmesartan and valsartan had a clear-cut antihypertensive effect. However,
      significantly earlier and more pronounced antihypertensive activity was achieved
      with valsartan than with olmesartan, as demonstrated by (1) significantly lower
      24-hour, daytime, and nighttime ABPM values after 2 weeks with valsartan (P<.01);
      (2) significantly lower percentage of abnormal BP readings with valsartan; (3)
      significantly higher trough-peak ratio and smoothness index with valsartan,
      suggesting a more prolonged and homogeneous antihypertensive effect; and (4)
      lower 24-hour postdose clinic systolic and diastolic BP values versus olmesartan.
      These findings show that pharmacodynamic and pharmacokinetic differences between
      AII receptor antagonists, at clinically comparable dosages, may be associated
      with differences in antihypertensive efficacy.

PMID- 15943221
TI  - Evaluation of prehospital emergency care in the field and during the ambulance
      drive to the hospital.
AB  - This study was conducted to evaluate the appropriateness of ambulance procedures
      and interventions in the management of patients dispatched to 2 emergency
      departments (EDs) of urban hospitals in Izmir. Use of trauma boards and cervical
      collars, airway patency, breathing, and circulation problems were recorded in
      both EDs. Eighty-one patients with a mean age of 47.54 +/- 2.36 years (range, 4
      89) brought into the ED via ambulances were enrolled in the study. Airway
      maneuvers were performed in patients with airway and breathing problems. There
      was no significant relationship between administration of IV fluids and the
      presence of circulatory impairment (P=.053). A trauma board was used in 9 of 30
      trauma cases (30%) and a cervical collar in 6 of 30 (20%). It was concluded that
      basic procedures used in the management of patients brought into the ED via
      ambulances were inadequate.

PMID- 15943222
TI  - Longitudinal assessment of the dose consistency of botulinum toxin type A (BOTOX)
      for cervical dystonia.
AB  - Botulinum toxin type A (BoNT/A) is the principal therapy for patients with
      cervical dystonia. Repeated treatments over many years are required in most
      cases. This retrospective review evaluates the dose of BoNT/A used to treat
      cervical dystonia and the interval between treatments during a 2-year observation
      period. Outcomes data were abstracted from the medical records of 172 patients at
      3 different sites who had received BoNT/A between January and December 1998. A
      total of 1059 treatments were assessed. Mean per-treatment doses throughout the 2
      year study ranged from 241.80 to 254.07 units. The mean interval between
      treatments was 108.48 days during the first year of observation and 114.14 days
      during the second year. These findings indicate that doses of and intervals
      between BoNT/A treatments for cervical dystonia were consistent throughout 2
      years of observation.

PMID- 15943223
TI  - A more reliable method for incudostapedial rebridging ossiculoplasty: bone cement
      and wire.
AB  - Polymaleinate glass ionomer cement is a commercially available bone cement (Ketac
      Cem Radiopaque, ESPE, Germany) that can be used to reconstruct a discontinuity
      between the incus and the stapes. The popularity of bone cement in otologic
      surgery is increasing. If the missing part of the incus is too long, the results
      in the long term could be unsatisfying. Under such circumstances, a new method of
      incudostapediopexy that uses wire and involves remodeling of the long process of
      the incus with bone cement is introduced. A retrospective analysis of the
      outcomes of incudostapedial rebridging ossiculoplasty (ISRO) procedures carried
      out in 21 patients between June 1999 and September 2003 was performed. A total of
      17 patients were treated with bone cement only; in 4 of these patients, hearing
      loss reoccurred within 6 months. The procedure was repeated in 2 of these
      patients using both bone cement and wire with satisfactory hearing results (air
      bone gaps, 7.5 and 8.8 decibels hearing level [dB HL]) after 1 year. Four
      patients underwent ISRO wire and bone cement initially. The long-term results of
      these 6 "wire-and-cement" cases, which were followed for a mean of 21 months,
      were satisfactory (air-bone gap, 9.8 dB HL). The postoperative air-bone gap in
      the 15 patients who were treated by ISRO with bone cement only excluding the 2
      reoperation cases was 12.1 dB HL. ISRO with bone cement is a cost-effective and
      safe procedure that yields good hearing results in selected cases. If the
      distance between eroded incus and stapes is too long to be reconstructed with
      bone cement alone, the surgeon should consider using wire with bone cement.

PMID- 15943224
TI  - Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic
      genistein (Bonistein) in healthy volunteers.
AB  - Genistein, an isoflavone and phytoestrogen predominantly found in soy, is
      considered a potentially safe therapeutic option to prevent postmenopausal bone
      loss. A novel purified product consisting of 99.4% synthetic genistein aglycone
      was investigated in a phase 1 clinical study to assess safety and tolerability in
      healthy volunteers as well as to obtain pharmacokinetic data. Single oral doses
      of 30, 60, 150, or 300 mg were administered to 40 healthy volunteers in this
      prospective, randomized, open-label and sequential-group study. Tolerability of
      the different genistein doses was very good. No clinically significant effects on
      vital signs, ECG, and clinical laboratory parameters were observed. Genistein was
      rapidly absorbed and the kinetic profiles revealed a one-peak plasma
      concentration-time course. Mean Cmax values of 252.0, 605.0, 1518.0, and 1808.0
      ng/mL were observed after 4.0 to 6.0 hours. The mean terminal elimination half
      lives were calculated to be 7.7, 7.5, 8.1, and 10.2 hours resulting in mean
      AUCs(0-infinity) of 2761.8, 8022.3, 21655.0, and 27537.8 ngxhr/mL. Linear
      regression of the dose-normalized AUCs(0-infinity) was not significantly
      different from zero, whereas the analysis for Cmax showed significance. Based on
      consecutive administration of single oral doses of genistein, dose linearity was
      assumed for extent of absorption [AUC(0-infinity)] for all doses (30-300 mg) and
      for rate of absorption (Cmax) up to 150 mg. At the highest dose the intestinal
      rate of absorption of genistein seemed to be limited. Genistein was safe and well
      tolerated in the dose range investigated and showed nearly dose-linear
      pharmacokinetic characteristics.

PMID- 15943225
TI  - [Effect of L-arginine on the endothelium functional activity in experimental
      diabetes mellitus].
AB  - The experimental data about the shift of L-arginine metabolism in the direction
      of activization of non-oxidizing (arginase) way under experimental diabetes
      mellitus are presented. This shift was proved by an increase of the ratio of
      arginase and NO-synthase activity and an increase of the ratio of their
      metabolites. The decrease of the free L-arginin contents in tissues of animals
      with experimental diabetes mellitus is shown. The long infusion of L-arginine
      results in the restoration of the endothelial function, however cessation of
      infusion results in a gradual reduction of this effect.

PMID- 15943226
TI  - [Effect of tonic painful squeezing of the finger distal joint on the evoked
      potential of different spectral frequency ranges in electroencephalogram of
      humans].
AB  - EEG changes caused by the tonic squeezing of the distal joint of the little
      finger of both hands were investigated on 12 healthy volunteers, age 20-56
      (average 35.5). Pain stimulation applied to the right hand was stronger than that
      applied to the left. Power spectra was measured in 7 EEG ranges: delta--2-4,
      theta1--4-6, theta2--6-8, alpha1--8-10.5, alpha2--10.5-13, beta1--13-20 and beta2
      -20-35 Hz. The increase of power in the different areas of the cerebral cortex
      was a dominant effect of pain influence in beta1 and beta2 as well as in both
      alpha-ranges. The pain stimulation influenced EEG-parameters bilaterally. It was
      supposed that increment of alpha-synchronization during peripheral pain reflected
      the inhibition processes in the thalamo-cortical system. This process most likely
      limited the area of afferent activation in the cortex. The topography of the
      significant power changes in alpha1- and alpha2-ranges was different during
      strong pain as well as after its cessation. Different parameters of functional
      brain activity during pain stimulation seemed to be reflected in alpha1- and
      alpha2-rhythms. The significant increment of spectral power in alpha-, beta- and
      theta2-ranges was demonstrated after cessation of strong pain in comparison to
      the pre-pain condition. Thus, the changes in EEG parameters reflect the latent
      and inertial character of the pain effects.

PMID- 15943227
TI  - [Phospholipid membrane modification as a protection factor of the myocardium
      during stress injury].
AB  - In experiments on the isolated rat hearts we investigated the influence of
      phospholipid membrane modification by omega-3 polyunsaturated fatty acids (PUFAs)
      on the heart reactivity to adrenergic influences, myocardial ultrastructure and
      peroxidation processes under the immobilization stress. It was shown that omega-3
      PUFAs reduced ultrastructural changes in the heart, limited lipid peroxidation
      and attenuated inotropic response of the heart to exogenous norepinephrine.

PMID- 15943228
TI  - [Central neuronal pathways in the Bezold-Jarisch reflex in rats].
AB  - The distribution of the Fos-immunoreactive (Fos-ir) and NADPH-diaphorase
      positive/NOS-containing neurons in the medulla and thoracic spinal cord in rats
      was studied after the veratrine injection into v. jugularis ext. followed by
      reproduction of the Bezold-Jarisch reflex. Fos-ir neurons were found in the
      nucleus tractus solitarius (Sol), coudoventrolateral (CVL) and
      rostroventrolateral (RVL) areas, intermediate reticular nucleus (IRt), and
      lateral paragiganrocellular nucleus (LPGi) of the medulla. The intensity of c-fos
      expression was as follows: Sol > CVL > RVL > LPGi. The intensity of NADPH
      diaphorase reactivity was manifested in the following sequence: Sol > IRt > LPGi
      > RVL. In comparison to sham-operated animals, application of veratrine is
      associated with a statistically significant increase (P < 0.01) of the mean
      number of Fos-ir neurons in the Sol and CVL, but not in the RVL. Double-labelling
      (Fos + NA DPH) was found in a small number (about 2%) of neurones in the Sol, IRt
      and LPGi. In the thoracic spinal cord Fos-ir neurons were predominantly detected
      in the superficial layers of the dorsal horn, area around the central canal and
      the intermediate lateral or medial nuclei (IMl and IMM), where NOS-containing
      neurons in the thoracic spinal cord were accumulated. Received data show that
      signals arising from the veratrine-activated cardiopulmonary afferents activate
      neurons of the Sol and CVL that together with the RVL are incorporated into
      neuronal circuits for generation of the Bezold-Jarisch reflex. In the medulla NOS
      containing neurons activated by input from cardiopulmonary receptors can
      contribute to the enhancement of cardioprotective depressor reflexes in the rats.

PMID- 15943229
TI  - [Allelic polymorphism of endothelial NO-synthase gene and its functional
      activity].
AB  - Investigation of phenotypic realization of the eNOS gene allelic polymorphism has
      shown that eNOS RNA content and eNOS activity in platelets depends on genotype.
      Using the reverse transcription and polymerase chain reaction it was shown that
      eNOS mRNA content is the lowest at -786C/C promoter's genotype. In exon 7
      homozygotes (894T/T) the RNA level is lower than in normal homozygotes (894G/G),
      but it is higher than in heterozygotes (894G/T). Contrary, at intron 4
      polymorphism the RNA level in the platelets from people with 4a/4a genotype is
      higher than in normal homozygotes and heterozygotes. Measuring of eNOS activity
      in platelets using diaminofluorescein diacetate (DAF-2A) showed that in carriers
      of 786C/C promoter genotype NO-producing activity is 2.1 times lower than in
      normal homozygotes (P=0.03) and 2.9 times lower comparing to heterozygotes
      (P>0.05). eNOS activity at 894T/T variant of 7-th exon is also lower than in
      normal homozygotes (P>0.05). Analogous data has been obtained while comparing
      eNOS activity at intron 4 polymorphism--enzyme activity was 1.7 times lower in
      carriers of 4a/4a genotype comparing to normal homozygotes (P>0.05) and 1.9 times
      lower than in heterozygotes (P>0.05). Data obtained permits to conclude, that T
      786-->C polymorphism of eNOS gene promoter effects the gene expression and eNOS
      activity the most significantly.

PMID- 15943230
TI  - [Analysis of heart rate variability in assessment of baroreflex sensitivity in
      anesthetized rats].
AB  - Spectral analysis of the heart rate variability can be used as a measure of
      baroreflex sensitivity in ketamine anesthetized rats. Stimulation of delta1
      receptors with phenylephrine (0.01 mg/kg, i.v.) results in a rise of the strength
      of heart rate regulation, principally in the low frequency band. Maximal
      deviations of spectral indexes from basal level were observed on 4-8 min for low
      (0.2-1 Hz) and high (1-3 Hz) frequencies bands and on 10-15 min for very low
      (0.08-0.2 Hz) frequency band after phenylephrine injection.

PMID- 15943231
TI  - [Electrophysiological study of tissue hydration in typical non-specific pulmonary
      pathology].
AB  - Computer occlusive electrical mioplethysmography and common electrical impedance
      meter method were used for the study of the tissue hydration in patients with
      bronchial asthma (BA) exposed to intermittent normobaric hypoxia (INH).
      Hyperhydration of intracellular and extracellular compartments in patients with
      BA was shown. INH significantly decreased tissue hyperhydration.

PMID- 15943232
TI  - [Comparative testing of analgesia induced by polarized light and analgetics].
AB  - In experiments on mice with the tonic pain locus the comparison of analgesia
      caused by the action of polarized light on an acupuncture point or by two classic
      analgetics (analginum, tramadol) was performed. The pain was evoked by hypodermic
      injection of formalin (30 ml of 5% solution) in the plantar region of hindlimb.
      Intensity of a pain was judged by duration of painful (licking of the pain locus)
      and non-painful (slipping, eating, running, washing) behavioral reactions for 60
      minutes of observation. In animals which received immediately after creation of
      the tonic pain locus a single intraperitoneal injection of analginum in a doze of
      4.2 mg/kg or 8.3 mg/kg the duration of pain response was reduced by 28.5% and
      74.9%, respectively. Tramadol decreased the duration of pain behavioral response
      by 34.2% and 56.2% in a dose 0.8 mg/kg and 8.3 mg/kg, respectively. Statistically
      significant attenuation of pain (by 50%) was observed in the group of animals
      exposed to a 10 minute session of polarized light on the antinociceptive acupoint
      A-36. Compare to animals that received high dozes of analgetics, activity and
      behavior in mice subjected to an polarized light differed less from the norm. It
      is possible to suppose, that polarized light will allow a reduction of
      pharmacological analgetics use and consequently will reduce the risk of
      development of undesirable side effects in clinic.

PMID- 15943233
TI  - [Immunopathophysiologic characteristics of early pregnancy in women with
      recurrent miscarriage].
AB  - The lymphocyte subsets, activation marker expression and activity of ConA-treated
      lymphocytes have been studied in 58 patients with a history of unexplainable
      pregnancy loss (UPL) and 22 normal pregnant women (control) in 4-7 weeks of
      pregnancy. The increase of CD16/56+ cell level and CD4+/ CD8+ ratio and decrease
      of CD19+ cell level have been found in peripheral blood of UPL patients in
      comparison with control. The expression of HLA-DR was upregulated on CD3+ and
      CD8+ cells and the expression of CD25 was downregulated on CD3+, CD4+, CD8+, and
      CD16/56+ cells in UPL women. According to correlation analysis results, low
      expression of CD25 was related to a low expression of CD8 on NK, high expression
      of CD45RA on CD4+ helper cells, high expression of HLA-DR on CD8+ cytotoxic
      cells. High frequency of ConA-induced activation, low frequency of ConA-induced
      suppression and low suppressive activity of ConA-induced lymphocyte were found in
      UPL patients compared to control. CONCLUSION: women with UPL have disorders in
      feto-maternal recognition in early pregnancy that led to a development of the
      inadequate immune response to fetus realized as a defect of NK activation,
      deficiency of T-cytotoxic cell limitation and memory helper cell generation,
      downregulation of TR cells and suppressor function.

PMID- 15943234
TI  - [Modulation of electrical and contractile responses of the isolated abdominal
      aorta in hyperholesterinemia and after treatment with calcium antagonists].
AB  - Membrane potential of aorta's endothelium, contractile responses of isolated
      preparation of the abdominal aorta and their modulation with calcium antagonists
      were studied at hypercholesterinemia (HHS). Membrane potential has been observed
      to be slightly depolarized at HHS, and acetylcholine-induced electric and
      contractile responses were shown to be depressed. Calcium antagonists had
      positive effect on MP, electric and contractile responses of the preparations of
      the abdominal aorta of rats with HHS. The most pronounced protective effect of
      membrane potential and contractile responses at HHS was observed in rats after
      asparcam using.

PMID- 15943235
TI  - [Formation of immunity and tolerance to the cell membrane components in primary
      and secondary (postimplantation) cardiac immunopathies].
AB  - The role of humoral constituents of the innate immunity in altering of tolerance
      and formation of immune response to autoreactive cell membrane components during
      both primary endocardithis and atherosclerosis processes and secondary ones,
      following reconstructive implantation on heart was investigated. The ways of
      restoration of the tolerance to membrane components and elimination of immune
      deficiency during the treatment of primary and secondary immunopathy of the
      cardiovascular system before and after implantation were considered.

PMID- 15943236
TI  - [Features of operated nerve regeneration under decompensated form of diabetes].
AB  - Work is devoted to a problem of the influence of diabetes on nervous system
      function, in particular, the regeneration of peripheral nerves. Chronic
      experiment were carried out on 8 mini-pigs (weight 35-40 kg) in two stages.
      Absolute insulin insufficiency was formed by total pancreatomy (the first stage);
      on the same day the sciatic nerve of an animal was severed 5-6 sm above its
      branching and sewed by perineural seam (the second stage). 60 days after
      neurorrhaphy a seam zone with the adjacent tissues was dissected for the
      investigation of morphological macro- and microscopic features of proximal and
      distal stump in the operated sciatic nerve, regenerative neuroma, micro
      circulating channel of a nerve, a connecting tissue of neural anastomosis and a
      nerve trunk as well as a level of synaptogenesis and a condition of separate
      muscles innervated by the operated nerve. The blood level of glucose and other
      biochemical parameters were assessed every three days. Macro- and microscopic
      examination testifies that the restoration of the operated nerve by sewing
      together of its ends under the decompensated diabetes, is considerably attenuated
      and is practically impossible during the late stages.

PMID- 15943237
TI  - [Mechanisms of adaptation to intermittent hypoxic training course in sportsmen of
      high qualification].
AB  - Normobaric intermittent hypoxic training (IHT) is an effective method for
      improvement of the FRS state, increase of the aerobic productivity, as well as
      general and special capacity for work in sportsmen of high qualification. High
      efficacy of IHT in improving all aspects of sportsmen FRS is a result of
      alternating the hypoxic influences and normoxic intervals between them during
      which the level of plastic processes remains increased, oxygen tension in
      arterial blood and tissues increases to nonnoxic values. After IHT course, the
      state of organ respiration improves, the respiration volume, a part of alveolar
      ventilation in the minute volume of respiration, oxygen saturation of arterial
      blood, hemoglobin content in blood--increase as well as economy and efficacy of
      oxygen regimes of organism, general and special (especially important) physical
      capacity for work.

PMID- 15943238
TI  - [Transformation of electrical activity in the myelinated nerve fibres of amphibia
      by 4-aminopyridine].
AB  - Using the extracellular recording we studied the effect of 4-aminopyridine (4
      AP), a potassium channel blocker on the electrical activity of the myelinated
      nerve fibres of amphibia Rana ridibunda Pallas. Two main types of the reaction on
      4-AP were established: extension of the action potential and multi-spike
      response. In some cases the nerve fibres with multi-spike response generated
      spontaneous activity without stimulation in the form of bursts of action
      potentials. During repetitive stimulation 4-AP decreased after-depolarization (at
      the beginning of the stimulation), the posttetanic after-depolarization and the
      development of posttetanic after-hyperpolarization. Using the paired stimulation
      it was established that the spike and after-depolarization of the second action
      potential depended on the size of after-depolarization after the first action
      potential. The effects of 4-AP were strongly time-dependent.

PMID- 15943239
TI  - [Estimation of individual levels of the physiological expenditures during mental
      work].
AB  - A new approach for determination of the individual levels of physiological
      expenditures in mental work is proposed. Comparison of adaptation reaction
      amplitude of cerebral arteries with the homeostatic range scale of
      cerebrovascular reactivity in human-operator gives the possibility to determine
      individual levels of the physiological expenditures in mental work. The
      homeostatic range of cerebrovascular reactivity was determined by hyper- and
      hypocapnia functional test. Using transcranial doppler the mean blood flow
      velocity in the middle cerebral artery was measured. Estimation of the
      individuals levels of physiological expenditures in mental work allows
      determination of the potential possibility of the individual person to perform
      this type of work.

PMID- 15943240
TI  - Phytoextraction: simulating uptake and translocation of arsenic in a soil-plant
      system.
AB  - The uptake, transport, and accumulation of metals by plants are functions central
      to successful phytoextraction. This study investigates the uptake and
      translocation of arsenic from a contaminated sandy soil by a mature Chinese brake
      fern (Pteris vittata L.). An existing mathematical model for the coupled
      transport of water, heat, and solutes in the soil-plant-atmosphere continuum
      (CTSPAC) was modified to examine the flow of water as well as the uptake and
      translocation of total arsenic in the xylem of the fern. This model was
      calibrated using greenhouse measurements before its application. Simulation
      results showed that about 20% of the soil arsenic was removed by the fern in 10
      d, of which about 90% of the arsenic was stored in the fronds and 10% in the
      roots. Although arsenic mass in the plant tissues increased consecutively with
      time, arsenic concentration in the xylem sap of the root tips has a typical
      diurnal distribution pattern: increasing during the day and decreasing at night,
      resulting from daily variations of frond surface water transpiration. The largest
      difference in simulated arsenic concentration in the root tips between the day
      and night was about 5%. This study also suggests that the use of transpiration
      stream concentration factor (TSCF), which is defined as the ratio of chemical
      concentration in the xylem sap to that in the external solution, to evaluate the
      translocation efficiency of arsenic for the hyperaccumulator Chinese brake fern
      (Pteris vittata L.) could be limited.

PMID- 15943241
TI  - Enhancing the growth of Vicia faba plants by microbial inoculation to improve
      their phytoremediation potential for oily desert areas.
AB  - Two experiments were conducted to investigate the effect of inoculating Vicia
      faba plants (broad beens) raised in clean and oily sand with nodule-forming
      rhizobia and plant-growth-promoting rhizobacteria (PGPR) on growth of these
      plants in sand and to test whether this can improve the phytoremediation
      potential of this crop for oily desert areas. It was found that crude oil in sand
      at concentrations < 1.0% (w/w) enhanced the plant heights, their fresh and dry
      weights, the total nodule weights per plant, and the nitrogen contents of shoots
      and fruits. Similar enhancing effects were recorded when roots of the young
      plants were inoculated with nodule bacteria alone, PGPR alone, or a mixture of
      one strain of nodule bacteria and one of the PGPR. Such plant growth effects were
      associated with a better phytoremediation potential of V. faba plants for oily
      sand. The total numbers of oil-utilizing bacteria increased in the rhizosphere
      and more hydrocarbons were eliminated in sand close to the roots. The nodule
      bacteria tested were two strains of Rhizobium leguminosarum and the PGPR were
      Pseudomonas aeruginosa and Serratia liquefaciens. The four strains were found to
      use crude oil, n-octadecane, and phenanthrene as sole sources of carbon and
      energy. It was concluded that coinoculation of V. faba plant roots in oily sand
      with nodule bacteria and PGPR enhances the phytoremediation potential of this
      plant for oily desert sand through improving plant growth and nitrogen fixation.

PMID- 15943242
TI  - Uptake and distribution of selenium in different fern species.
AB  - There has been an interest in using hyperaccumulating plants for the removal of
      heavy metals and metalloids. High selenium (Se) concentrations in the environment
      are detrimental to animals, humans, and sustainable agriculture, yet selenium is
      also an essential nutrient for humans. This experiment was conducted to screen
      fern plants for their potential to accumulate selenium. Eleven fern species,
      Pteris vittata, P. quadriaurita, P. dentata, P. ensiformis, P. cretica,
      Dryopteris erythrosora, Didymochlaena truncatula, Adiantum hispidulum,
      Actiniopteris radiata, Davallia griffithiana, and Cyrtomium fulcatum, were grown
      under hydroponic conditions for one week at 20 mg L(-1) selenate or selenite.
      Root Se concentrations reached 245-731 and 516-1082 mg kg(-1) when treated with
      selenate and selenite, respectively. The corresponding numbers in the fronds were
      153-745 and 74-1,028 mg kg(-1) with no visible toxicity symptoms. Only three fern
      species were able to accumulate more Se in the fronds than the roots, which were
      D. griffithiana when treated with selenate, P. vittata when treated with
      selenite, and A. radiata regardless of the forms of Se. A. radiata was the best
      species overall for Se accumulation. More research is needed to further determine
      the potential of the fern species identified in this study for phytoremediation
      of the Se contaminated soils and water.

PMID- 15943243
TI  - Effect of simultaneous establishment of Sedum alfredii and Zea mays on heavy
      metal accumulation in plants.
AB  - Land application of biosolids to improve agricultural productivity is a cost
      effective approach for resource recovery. Unfortunately, municipal biosolids
      often contain high concentrations of heavy metals, including zinc and copper. In
      this study, a co-cropping technique was investigated using a known zinc
      hyperaccumulator, Sedum alfredii with a grain crop, Zea mays. After a 3-mo growth
      trial, the results indicate that when Z. mays is co-cropped with S. alfredii,
      heavy metals accumulated in the grains were significantly reduced when compared
      to monoculture cropping. Co-cropping improved the growth of both plant species.
      In addition, the biosolids maintained stable pH, N-P-K concentrations,
      germination potential, and water content after the plant treatment, regardless of
      the plant species used in the trial. In conclusion, co-cropping with
      hyperaccumulators may be an effective approach to reducing the risk of
      contaminant uptake in edible crops.

PMID- 15943244
TI  - Effect of thallium fractions in the soil and pollution origins on Tl uptake by
      hyperaccumulator plants: a key factor for the assessment of phytoextraction.
AB  - Phytoremediation is often discussed as a means of extracting trace metals in
      excess in the soil, but to increase its efficiency a better understanding of the
      factors controlling plant uptake is required. The main objective of this study
      was to examine the effect of origin (anthropogenic vs. geogenic) and mobility of
      thallium (Tl) in the rhizosphere on Tl uptake. Two Tl-hyperaccumulating
      Brassicaceae species, kale (Brassica oleracea acephala L. cv. Winterbor F1) and
      candytuft (Iberis intermedia Guers.), were grown in a rhizobox system to
      investigate the dynamics of Tl in the rhizosphere soil. Four different soils were
      used. Two soils contained high Tl amounts due to anthropogenic sources (emissions
      from a cement plant and mining activities). High Tl content in the two other
      soils was due to a high rock content (geogenic origin). On completion of growth
      in the rhizoboxes, the depletion of Tl in seven different chemical fractions,
      determined by sequential extraction, was compared to the plant uptake. Most of
      the Tl taken up was derived from the so-called "easily accessible" fractions in
      both soils with geogenic Tl as well as in the soils polluted by mining
      activities. Due to the small amounts of easily accessible Tl in the geogenic
      soils, Tl uptake by Brassicaceae was low. On the other hand, for the air emission
      polluted soil, a high depletion of Tl from "less accessible" fractions was
      observed in addition to depletion of the easily accessible fractions. Hence, the
      latter soil demonstrated the highest potential for effective soil decontamination
      by phytoextraction within an appropriate time frame.

PMID- 15943246
TI  - Design, optical characterization, and operation of large transmission gratings
      for the laser integration line and laser megajoule facilities.
AB  - Within the framework of the laser integration line (LIL) and the laser megajoule,
      we describe the design, optical characterization, mounting, alignment, and
      operation on the LIL of large 420 mm x 470 mm transmission gratings. Two types of
      grating were manufactured. The first, operating at a wavelength of 1.053 microm,
      was used for deviation purposes. The second, operating at a wavelength of 0.351
      microm, was used for both deviation and focusing purposes. We demonstrate that
      these large transmission gratings are suitable for nanosecond-regime operation on
      high-power laser facilities.

PMID- 15943245
TI  - Phytoextraction of copper from contaminated soil by Elsholtzia splendens as
      affected by EDTA, citric acid, and compost.
AB  - Phytoextraction of copper (Cu) from contaminated soils greatly depends on the
      metal bioavailability in the soils and metal uptake ability of the plant. In this
      study, the effects of chelators [ethylenediamine tetraacetic acid (EDTA), citric
      acid (CA)] and compost amendments on Cu phytoextraction potential by a tolerant
      and accumulating plant species (E. splendens) were examined in two types of
      contaminated soils, ie., the mined soil from Cu-mined area (MS) and a paddy soil
      polluted by Cu refining (PS). The results showed that EDTA application at 2.5-5.0
      mmol kg(-1) increased phytoextraction of Cu by four- and eight-fold from both MS
      and PS, respectively, which is mainly attributed to increased H2O extractable Cu
      in the soil. The Cu amount extracted by the shoots of E. splendens reached 800
      1000 microg Cu plant(-1) from the MS and 400-700 microg Cu plant(-1) from the PS
      at EDTA application rates of 2.5-5.0 mmol kg(-1). The application of CA at 5.0
      mmol kg(-1) had minimal effects on Cu extractability in both soils and slightly
      decreased Cu extraction efficiency by E. splendens. Plant biomass production was
      enhanced by CA at 0.25 mmol L(-1) in nutrient solution, but inhibited by CA at
      5.0 mmol kg(-1) in both MS and PS. Increasing the compost rate significantly
      decreased H2O extractable Cu in the MS, but raised H2O-extractable Cu in the PS,
      which resulted mainly front the reduced exchangeable Cu in the MS and the
      increased exchangeable and organic fractions of Cu in the PS by compost. At high
      compost rate (5%), the shoots of E. splendens extracted 3.6-fold higher Cu from
      the PS than from the MS. These results indicate that, among the soil amendments,
      efficiency of Cu phytoextraction is enhanced mostly by 2.5-5.0 mmol kg(-1) EDTA,
      followed by 5% (w:w) compost, whereas < 5.0 mmol kg(-1) CA has minimal effects on
      Cu phytoextraction by E. splendens in the PS. As for the MS, only 2.5-5.0 mmol
      kg(-1) EDTA can elevate the efficiency of Cu, while 5% compost amendment and <
      5.0 mmol kg(-1) CA application have no marked effects on Cu phytoextraction by E.
      splendens.

PMID- 15943247
TI  - Determination of optical birefringence by using off-axis transmission
      ellipsometry.
AB  - Utilizing transmission ellipsometry at small angles of incidence, it is shown
      that c-cut uniaxial samples can be used to determine both the miscut of the optic
      axis with respect to the plane of incidence as well as very accurate values of
      the spectroscopic birefringence. For example, wafers of ZnO, LiNbO3, and 6H-SiC
      single-crystals are examined and the miscut direction and the spectroscopic
      birefringence are determined. While all materials show strong dispersion in
      birefringence, ZnO exhibits a distinct isotropic point at 396.8 nm.

PMID- 15943248
TI  - Application of space periodic variation of light polarization in imaging
      polarimetry.
AB  - The application of space periodic variation of light polarization for measurement
      and calculation of the distribution of the phase retardation between two
      eigenwaves propagating inside a linearly birefringent media and the distribution
      of the azimuth angle of the first eigenvector is described. The measuring method
      proposed does not require any mechanical movements or rotations of any optical
      elements. Application of a liquid crystal (LC) modulator instead of a quarter
      wave plate gives an opportunity to introduce the required phase shift. The space
      periodic modulation of the polarization of light is achieved by the use of a
      Wollaston prism placed inside the path of the light beam. Then a fast Fourier
      transform is used for further calculations. The number of measurements of the
      light intensity at the output of the system is minimized to two. These
      assumptions make the proposed method very fast, which is especially important in
      measurements of the objects with optical anisotropy that is changing in time.

PMID- 15943249
TI  - Optical pump-and-probe test system for thermal characterization of thin metal and
      phase-change films.
AB  - A single-shot optical pump-and-probe test system is reported. The system is
      designed for thermal characterization of thin-film samples that can change their
      phase state under the influence of a short and intense laser pulse on a
      subnanosecond time scale. In combination with numerical analysis, the system can
      be used to estimate thermal constants of thin films, such as specific heat and
      thermal conductivity. In-plane and out-of plane thermal conductivity can be
      estimated independently. The system is intended for use in research on optical
      data storage and material processing with pulsed laser light. The system design
      issues are discussed. As application examples, we report on using the system to
      study thermal dynamics in two different thin-film samples: a gold film on a glass
      substrate (a single-phase system) and the quadrilayer phase-change stack typical
      in optical data-storage applications.

PMID- 15943250
TI  - Construction of refractive-index profiles of planar waveguides with additional
      information obtained from surface plasmon resonance.
AB  - A surface plasmon resonance (SPR) is excited between a metal film and a graded
      index planar waveguide. After the propagation constant of the SPR is measured,
      the refractive index near the surface of the waveguides, which is difficult to
      obtain by conventional techniques, is determined experimentally. With this
      nondestructive technique, combined with the inverse analytical transfer matrix
      method, the planar waveguide can be profiled to a high degree of accuracy.

PMID- 15943251
TI  - Development of a frequency-detuned interferometer as a prototype experiment for
      next-generation gravitational-wave detectors.
AB  - We report on our prototype experiment that uses a 4-m detuned resonant sideband
      extraction interferometer with suspended mirrors, which has almost the same
      configuration as the next-generation, gravitational-wave detectors. We have
      developed a new control scheme and have succeeded in the operation of such an
      interferometer with suspended mirrors for the first time ever as far as we know.
      We believe that this is the first such instrument that can see the radiation
      pressure signal enhancement, which can improve the sensitivity of next-generation
      gravitational-wave detectors.

PMID- 15943252
TI  - Modeling and analysis of an extrinsic Fabry-Perot interferometer cavity.
AB  - A schematic representation of optical feedback between two resonator mirrors
      undergoing a phase shift each round trip as a function of the separation of the
      mirrors is studied. A transfer function modeling of the extrinsic Fabry-Perot
      interferometer (EFPI) is presented. Nyquist analysis has been used to forecast
      the operational stability and possibility of interference in an EFPI. The
      analysis with two perfectly parallel surfaces of the cavity shows efficient
      interference. The performance when there is some tilt between the two mirrors in
      the cavity is also studied and is presented. In this case some restricted
      interference is found.

PMID- 15943253
TI  - Microholographic multilayer optical disk data storage.
AB  - Micrometer-sized reflection holograms can be written into a rapidly rotating
      homogeneous photopolymer disk at the focus of a high-numerical-aperture beam and
      its retroreflection to implement high-capacity multilayer digital data storage.
      This retroreflection is generated by an optical system with positive unity
      magnification to ensure passive alignment of the counterpropagating beam.
      Analysis reveals that the storage capacity and transfer rate of this bit-based
      holographic storage system compare favorably with traditional page-based systems
      but at a fraction of the system complexity and cost. The analysis is
      experimentally validated at 532 nm by writing and reading 12 layers of
      microholograms in a 125-microm photopolymer disk continuously rotating at 3600
      rpm. The experimental results predict a capacity limit of 140 Gbytes in a
      millimeter-thick disk or over 1 Tbyte with the wavelength and numerical aperture
      of Blu-Ray.

PMID- 15943254
TI  - Thermal illuminators for far-infrared and submillimeter astronomical instruments.
AB  - Astronomical instruments operating in the infrared-millimeter region often
      require internal sources for detector monitoring, instrument calibration, and
      health checking. We describe the design, modeling, and experimental evaluation of
      thermal emitters with a fast speed of response and low-power dissipation,
      suitable for the far-infrared-submillimeter region. The development of an
      internal illuminator for the Herschel Spectral and Photometric Imaging Receiver
      (SPIRE) satellite instrument is used as an example of the optimization of the
      design to meet particular requirements. A prototype illuminator design for SPIRE
      has been developed that, for a power dissipation of 1.5 mW, provides an
      equivalent blackbody temperature of 45 K with a 90% settling time of 220 ms.

PMID- 15943255
TI  - Effect of the azimuthal orientation on the performance of grating-coupled surface
      plasmon resonance biosensors.
AB  - The effect of azimuthal orientation on the electromagnetic coupling of surface
      plasmons with the incident and diffracted light of a grating-coupled surface
      plasmon resonance (GC-SPR) biosensor is investigated, and its practical
      implications are explored. For this purpose a GC-SPR biosensor model is
      considered, and well-established rigorous coupled-wave analysis is used.
      Numerical results indicate significant variations in surface-plasmon resonance
      characteristics in connection with the interaction between surface-plasmon
      polaritons associated with multiple-order diffraction. The results are discussed
      as they relate to applications that require minimal rotation sensitivity.

PMID- 15943256
TI  - Waveguide analysis of organic light-emitting diodes fabricated on surfaces with
      wavelength-scale periodic gratings.
AB  - Numerical techniques for the analysis of multilayer waveguide structures were
      used to study the modes that exist in organic light-emitting diode (OLED)
      devices. The analysis revealed that waveguide modes of the OLED structure could
      be grouped, according to the behavior of modal-field profiles in the air cover
      and the glass substrate, into one of four different "families": (i) bound mode,
      (ii) semibound modes, (iii) leaky modes, and (iv) nonphysical modes. Four
      different OLED samples were fabricated on glass substrates on which photoresist
      gratings had been previously formed. The theory was used to compute the angles at
      which light from these devices should exit into the air. Theory and data agreed
      well for the semibound modes for all samples; however, they did not agree so well
      for the leaky modes. Further investigation revealed that better agreement between
      theory and data could be obtained with these modes being analyzed as Fabry-Perot
      cavity modes. The theoretical relation between leaky waveguide modes and Fabry
      Perot cavity modes is discussed.

PMID- 15943257
TI  - Tunable microfluidic microlenses.
AB  - A novel type of liquid microlens, bounded by a microfabricated, distensible
      membrane and activated by a microfluidic liquid-handling system, is presented. By
      use of an elastomer membrane fabricated by spin coating onto a dry-etched silicon
      substrate, the liquid-filled cavity acts as a lens whereby applied pressure
      changes the membrane distension and thus the focal length. Both plano-convex and
      plano-concave lenses, individual elements as well as arrays, were fabricated and
      tested. The lens surface roughness was seen to be approximately 9 nm rms, and the
      focal length could be tuned from 1 to 18 mm. This lens represents a robust, self
      contained tunable optical structure suitable for use in, for example, a medical
      environment.

PMID- 15943258
TI  - Operator representation as a new differential optical absorption spectroscopy
      formalism.
AB  - UV-visible absorption spectroscopy with extraterrestrial light sources is a
      widely used technique for the measurement of stratospheric and tropospheric trace
      gases. We focus on differential optical absorption spectroscopy (DOAS) and
      present an operator notation as a new formalism to describe the different
      processes in the atmosphere and the simplifying assumptions that compose the
      advantage of DOAS. This formalism provides tools to classify and reduce possible
      error sources of DOAS applications.

PMID- 15943259
TI  - Metal-substituted organic Cd-arachidate multilayers as soft-x-ray mirrors.
AB  - Multilayers for soft x rays, lambda > 4.5 nm, have been made with Cd arachidate,
      a metal-substituted fatty acid. The multilayer period is found to be 5.53 nm,
      double the normal length of a Cd-arachidate molecule. The interfaces have a low
      roughness value of < 0.3 nm, which does not reduce the long-wavelength
      reflectance significantly. The soft-x-ray reflectance at 3.0 nm has been measured
      to be 0.13% for this prototypical multilayer that has 12 bilayers. The
      theoretical reflectance of these multilayers determined at a wavelength of 10.0
      nm, suitable for x-ray lithography, is found to saturate at approximately 43% for
      approximately 150 bilayers.

PMID- 15943260
TI  - Coherence-contrast x-ray imaging based on x-ray interferometry.
AB  - Coherence-contrast x-ray imaging--which detects changes in the degree of
      coherence caused by the placement of a sample in an x-ray interferometer--was
      developed for biomedical applications. Because the technique's sensitivity
      depends on the density gradient in the sample, it is particularly suitable for
      observing biomedical samples with large density differences, such as samples that
      include both biological soft tissue and bone. A measurement principle and method
      of this technique are described, and a fine coherence-contrast image of a mouse
      leg is given as an example result.

PMID- 15943261
TI  - Fluorescence correlation microscopy with real-time alignment readout.
AB  - In confocal fluorescence correlation microscopy (FCM) it is important to ensure
      that the correlation measurement is actually performed at the chosen location of
      the three-dimensional image of the specimen. We present a confocal FCM design
      that provides an automatic real-time readout of the location in the confocal
      microscopic image, which is aligned with the detector of the fluorescence
      correlation spectrometer. The design accomplishes this without using any special
      positioning device. The design is based on an apertured fluorescence detector
      placed close to the back aperture of the objective lens and can be easily
      incorporated into virtually any confocal microscope. We demonstrate the method by
      performing FCM measurements of a dye diffusing on a cell membrane.

PMID- 15943262
TI  - Characteristics of calculus fragmentation with Er:YAG laser light emitted by an
      infrared hollow optical fiber with various sealing caps.
AB  - We have experimentally quantified calculus fragmentation by Er:YAG laser light.
      Er:YAG laser light was delivered to an underwater target through a sealed hollow
      optical fiber. Fragmentation efficiency was obtained for an alumina ball used as
      a calculus model when sealing caps with various focusing effects were used. Three
      types of human calculus were analyzed, and their absorption properties at the
      wavelength of Er:YAG laser light were obtained. The relationships among the
      absorption properties, calculus constituents, and fragmentation efficiency are
      discussed.

PMID- 15943263
TI  - Observation of a stacking process of microparticles with multiple beams.
AB  - We developed a method of constructing a stacked structure of microparticles by
      using multiple beams emitted by a vertical-cavity surface-emitting laser array
      [Appl. Phys. Lett. 82, 2969 (2003)]. We construct a new observation system to
      observe the stacked structure and to clarify the stacking process. Results
      confirmed that the stacked structure was lifted up from the sample stage and
      fabricated without space between the microparticles. Furthermore, we investigated
      the difference of stacking processes when 2 x 2 beams and a single beam were
      used. As a result, we found that a stacked structure, when 2 x 2 beams were used,
      can be fabricated with lower optical power than when a single beam was used.

PMID- 15943264
TI  - Determination of the optimum sampling frequency of noisy images by spatial
      statistics.
AB  - In optical metrology the final experimental result is normally an image acquired
      with a CCD camera. Owing to the sampling at the image, an interpolation is
      usually required. For determining the error in the measured parameters with that
      image, knowledge of the uncertainty at the interpolation is essential. We analyze
      how kriging, an estimator used in spatial statistics, can generate convolution
      kernels for filtering noise in regularly sampled images. The convolution kernel
      obtained with kriging explicitly depends on the spatial correlation and also on
      metrological conditions, such as the random fluctuations of the measured
      quantity, and the resolution of the measuring devices. Kriging, in addition,
      allows us to determine the uncertainty of the interpolation, and we have analyzed
      it in terms of the sampling frequency and the random fluctuations of the image,
      comparing it with Nyquist criterion. By use of kriging, it is possible to
      determine the optimum-required sampling frequency for a noisy image so that the
      uncertainty at interpolation is below a threshold value.

PMID- 15943265
TI  - Profiling of objects with height steps by wavelet analysis of shadow moire
      fringes.
AB  - A temporal wavelet analysis algorithm is proposed for shadow-moire-based three
      dimensional surface profiling on objects having discontinuous height steps. A
      grating is positioned close to an object, and its shadow is observed through the
      grating. The moire fringe patterns vary when the grating is in-plane rotating. A
      series of fringe patterns are captured by a CCD camera at different rotating
      angles. Phase values are evaluated point by point with the continuous wavelet
      transform. From the phase values of each point on the object, the distance
      between the object and the grating can be retrieved. The surface profile is
      obtained without temporal or spatial phase unwrapping. This technique is
      applicable to objects with discontinuous height steps, which are impossible to
      measure with conventional shadow moire topography. Two specimens are tested to
      demonstrate the validity of the method: One is an object with a height step of
      1.6 mm, and another is a small coin with unevenness of less than 0.2 mm. The
      experimental results are compared with test results by use of the mechanical
      stylus method.

PMID- 15943266
TI  - Tomographic retrieval of atmospheric parameters from infrared limb emission
      observations.
AB  - Typical inversion of limb-sounding measurements assumes local horizontal
      homogeneity of the atmosphere. This simplification corresponds to spectral
      radiance errors that can exceed the noise level of a typical infrared instrument
      by a factor of 10 and causes errors in retrieved state parameters. To avoid these
      errors and to take the horizontal structure of the atmosphere into account, a two
      dimensional (2D) tomographic sequential estimation approach is described.
      Application to temperature retrievals from simulated measurements yields typical
      retrieval errors of the order of 1 K, and a one-dimensional retrieval with the
      same synthetic measurements shows differences to the true values up to 10 K in
      regions with strong horizontal inhomogeneities. The horizontal resolution of the
      2D retrieval is even better (up to 40 km) than the horizontal tangent point
      spacing.

PMID- 15943267
TI  - Determination of polar stratospheric cloud particle refractive indices by use of
      in situ optical measurements and T-matrix calculations.
AB  - A new algorithm to infer structural parameters such as refractive index and
      asphericity of cloud particles has been developed by use of in situ observations
      taken by a laser backscattersonde and an optical particle counter during balloon
      stratospheric flights. All three main particles, liquid, ice, and a no-ice solid
      (NAT, nitric acid trihydrate) of polar stratospheric clouds, were observed during
      two winter flights performed from Kiruna, Sweden. The technique is based on use
      of the T-matrix code developed for aspherical particles to calculate the
      backscattering coefficient and particle depolarizing properties on the basis of
      size distribution and concentration measurements. The results of the calculations
      are compared with observations to estimated refractive indices and particle
      asphericity. The method has also been used in cases when the liquid and solid
      phases coexist with comparable influence on the optical behavior of the cloud to
      estimate refractive indices. The main results prove that the index of refraction
      for NAT particles is in the range of 1.37-1.45 at 532 nm. Such particles would be
      slightly prolate spheroids. The calculated refractive indices for liquid and ice
      particles are 1.51-1.55 and 1.31-1.33, respectively. The results for solid
      particles confirm previous measurements taken in Antarctica during 1992 and
      obtained by a comparison of lidar and optical particle counter data.

PMID- 15943268
TI  - Mapping tropospheric ozone profiles from an airborne ultraviolet-visible
      spectrometer.
AB  - We present a novel technique for retrieving ozone (O3) profiles and especially
      tropospheric O3 from airborne UV/visible spectrometer measurements. This
      technique utilizes radiance spectra from one down-looking and two up-looking (85
      degrees and 75 degrees) directions, taking advantage of the O3 absorption
      structure in the Huggins (300-340-nm) and Chappuis (530-650-nm) bands. This
      technique is especially sensitive to tropospheric O3 below and < or =8 km above
      the aircraft with a vertical resolution of 2-6 km and is sensitive to lower and
      middle stratospheric O3 with a vertical resolution of 8-15 km. It can measure
      tropospheric O3 at spatial resolutions of 2 km x 2 km or higher and is therefore
      well suited for regional air-quality studies and validation of satellite
      measurements.

PMID- 15943269
TI  - Improved algorithm for calculations of Rayleigh-scattering optical depth in
      standard atmospheres.
AB  - Precise calculations of the total Rayleigh-scattering optical depth have been
      performed at 88 wavelengths ranging from 0.20 to 4.00 microm for the six well
      known standard atmosphere models by integrating the volume Rayleigh-scattering
      coefficient along the vertical atmospheric path from sea level to a 120-km
      height. The coefficient was determined by use of an improved algorithm based on
      the Ciddor algorithm [Appl. Opt. 35, 1566 (1996)], extended by us over the 0.20
      0.23-microm wavelength range to evaluate the moist air refractive index as a
      function of wavelength, air pressure, temperature, water-vapor partial pressure,
      and CO2 volume concentration. The King depolarization factor was also defined
      taking into account the moisture conditions of air. The results indicate that the
      influence of water vapor on Rayleigh scattering cannot be neglected at
      tropospheric altitudes: for standard atmospheric conditions represented in terms
      of the U.S. Standard Atmosphere (1976) model, the relative variations produced by
      water vapor in the Rayleigh scattering parameters at a 0.50-microm wavelength
      turn out to be equal to -0.10% in the moist air refractivity at sea level (where
      the water-vapor partial pressure is equal to approximately 7.8 hPa), -0.04% in
      the sea-level King factor, -0.24% in the sea-level Rayleigh-scattering cross
      section, and -0.06% in the Rayleigh-scattering optical depth.

PMID- 15943270
TI  - Graded-index silver chlorobromide fibers for the mid-infrared.
AB  - We have developed and characterized graded-index optical fibers for the mid-IR
      spectral range, based on silver chlorobromide (AgClBr) crystals. A preform was
      fabricated by inserting a cylindrical rod made of AgCl(0.1)Br(0.9) into a tube
      made of AgCl(0.9)Br(0.1). The preform was heated in an oven, causing diffusion of
      Cl into the outer layer of the rod, thus reducing its index of refraction. The
      rod was removed from the tube and was then extruded through a die to form a
      graded-index fiber. Such a fiber was analyzed, investigated, and compared with a
      step-index fiber made of AgClBr. The attenuation of a 0.9-mm-diameter graded
      index fiber was found to be 2.4 dB/m, and the attenuation of a 1.2-mm-diameter
      graded-index fiber was 4 dB/m at 10.6 microm.

PMID- 15943271
TI  - Limits on the performance of dispersive thin-film stacks.
AB  - Dispersive thin-film stacks are interesting as compact, cost-effective devices
      for temporal dispersion compensation and wavelength multiplexing. Their
      performance depends on the total group delay or spatial shift that can be
      achieved. For general multilayer stacks, no analytic model exists relating the
      performance to the stack parameters such as the refractive indices and the number
      of layers. We develop an empirical model by designing and analyzing 623 thin-film
      stacks with constant dispersion. From this analysis we conclude that, for given
      stack parameters, the maximum constant dispersion value is inversely proportional
      to the wavelength range over which the dispersion is achieved. This is equivalent
      to saying that, for constant dispersion, there is a maximum possible spatial
      shift (or group delay) that can be achieved for a given material system and
      number of layers. This empirical model is useful to judge the feasibility of
      dispersive photonic nanostructures and photonic crystal superprism devices and
      serves as a first step in the search for an analytic performance model. We
      predict that an 8-channel wavelength multiplexer can be realized with a single 21
      microm-thick SiO2-Ta2O5 thin-film stack.

PMID- 15943272
TI  - Ion-exchanged glass waveguides with low birefringence for a broad range of
      waveguide widths.
AB  - Optical communications networks require integrated photonic components with
      negligible polarization dependence, which typically means that the waveguides
      must feature very low birefringence. Recent studies have shown that waveguides
      with low birefringence can be obtained, e.g., by use of silica-on-silicon
      waveguides or buried ion-exchanged glass waveguides. However, many integrated
      photonic circuits consist of waveguides with varying widths. Therefore low
      birefringence is consequently required for waveguides having different widths.
      This is a difficult task for most waveguide fabrication technologies. We present
      experimental results on waveguide birefringence for buried silver-sodium ion
      exchanged glass waveguides. We show that the waveguide birefringence of the order
      of 10(-6) for waveguide mask opening widths ranging from 2 to 10 microm can be
      obtained by postprocessing the sample through annealing at an elevated
      temperature. The measured values are in agreement with the values calculated with
      our modeling software for ion-exchanged glass waveguides. This unique feature of
      ion-exchanged waveguides may be of significant importance in a wide variety of
      integrated photonic circuits requiring polarization-independent operation.

PMID- 15943273
TI  - Phased array 1-to-N-way resonator with a convex mirror for phase conjugation.
AB  - Phased array 1-to-N-way resonators can be relevant in the realization of high
      output powers from semiconductor laser arrays and have significant advantages
      over Talbot resonators. However, depending on the number of array elements, the
      intracavity power density on the output facet can be high, resulting in
      catastrophic optical mirror damage. We present a variant of the original design
      that overcomes these power density problems while maintaining the desirable phase
      locking and power-combining properties.

PMID- 15943274
TI  - Narrow resonances and ripple fluctuations in light scattering by a spheroid.
AB  - We develop a semiclassical theory to explain the rapid ripple fluctuations in the
      extinction efficiency of light scattering by a transparent prolate spheroid. The
      theory is based on uniform asymptotic expansion of spheroidal radial functions.
      We have calculated the extinction efficiency for normal and oblique incidence.
      Our results suggest that the excitation of resonant electromagnetic modes inside
      a spheroidal particle is an important factor in the ripple structure. To verify
      this assumption and based on a Breit-Wigner formula, we develop a method to fit
      the peaks that appear in the spheroid's extinction cross section when some
      scattering parameters vary. In other words, our calculations suggest that narrow
      resonances are related to ripple fluctuations, whereas broad resonances
      contribute to extinction cross-sectional background.

PMID- 15943275
TI  - Characterization of ultrashort pulses by a modified grating-eliminated no
      nonsense observation of ultrafast incident laser light E fields (GRENOUILLE)
      method.
AB  - The measurement and characterization of ultrashort laser pulses remains an
      arduous task. The most commonly used pulse-measurement method is known as
      frequency-resolved optical gating (FROG), and another version with great
      experimental simplification and low-priced setup is known as grating-eliminated
      no-nonsense observation of ultrafast incident laser light E fields (GRENOUILLE).
      Nevertheless, there is interest in elaborating other, more accessible or simpler
      and cheaper, setups with equal or better assets. We explored modification of the
      GRENOUILLE method in which we replaced the original Fresnel biprism with a beam
      splitter and two mirrors and used a cheap webcam to measure the pulse traces. We
      have evaluated our system, and we propose a method to correct border effects
      caused by the beam intensity's profile based on the characterization of three
      pulse classes: Fourier-transform limited, double, and chirped. We compare the
      recovered electric field with further spectral and second-order correlation data
      of the corresponding pulses.

PMID- 15943276
TI  - Underwater cytometer for in situ measurement of marine phytoplankton by a
      technique combining laser-induced fluorescence and laser Doppler velocimetry.
AB  - We present a new type of flow cytometer that can operate underwater for a long
      time, as long as days, for measuring the size distribution, concentration, and
      biomass of marine phytoplankton. The major improvement of the instrument over
      existing techniques is the elimination of sample preparation, which is achieved
      with a laser Doppler crossed-beam arrangement for both defining a measurement
      volume and measuring the speed of the particle traversing it. By simultaneously
      sampling the laser-induced fluorescence signal and the Doppler signals, the
      technique can discriminate sizes of phytoplankton.

PMID- 15943277
TI  - Optimal beams for propagation through random media.
AB  - The problem of maximizing the intensity that is transferred from a transmitter
      aperture to a receiver aperture is considered in which the propagation medium is
      random. Two optimization criteria are considered: maximal expected intensity
      transfer and minimal scintillation index. The beam that maximizes the expected
      intensity is shown to be fully coherent. Its coherent mode is determined as the
      principal eigenfunction for a kernel that is determined through the second-order
      moments of the propagation Green's function. The beam that minimizes the
      scintillation index is shown to be partially coherent in general, with its
      coherent modes determined by minimizing a quadratic form that has nonlinear
      dependence on the coherent-mode fields, and on the second- and fourth-order
      moments of the propagation Green's function.

PMID- 15943278
TI  - Geometrical phase image encryption obtained with space-variant subwavelength
      gratings.
AB  - An optical encryption method based on a geometrical phase produced by space
      variant polarization manipulation is presented. The decrypted picture is
      retrieved either by a polarization measurement of the beam emerging from the
      encrypted element or by a single intensity measurement of the beam transmitted
      through the encrypted element followed by an optical key element. Both elements
      are realized by use of computer-generated space-variant subwavelength dielectric
      gratings. Theoretical analyses of the optical concept are presented along with
      experimental results.

PMID- 15943279
TI  - Subpeaks in the Brillouin loss spectra of distributed fiber-optic sensors.
AB  - Subpeaks in the Brillouin loss spectra of distributed fiber-optic sensors were
      observed for what is believed to be the first time and studied. We discovered
      that the Fourier spectrum of the pulsed signal and the off-resonance oscillation
      both contributed to subpeaks. The off-resonance oscillation at frequency /v - vB/
      is the oscillation in the Brillouin time domain when beat frequency v of the two
      counterpropagating laser beams does not match local Brillouin frequency vB. This
      study is important in differentiating the subpeaks from actual strain-temperature
      peaks.

PMID- 15943280
TI  - Birefringent interleaver with a ring cavity as a phase-dispersion element.
AB  - We propose and demonstrate a novel ring-cavity-based flat-top birefringent
      interleaver. A single ring cavity provides the two phase shifts needed, each for
      a polarization state, to achieve a flat-top spectral passband at the output.
      Fresnel reflectivities (for s- and p-polarization states) at the prism interface
      of the ring cavity are employed so that highly accurate thin-film coatings are
      not needed for the phase shifts. By choosing the appropriate incident angle near
      the Brewster angle, we can obtain the optimum interface reflectivities for flat
      passbands and extremely low cross talk. We also present the results of our
      experimental investigations of a flat-top 25-GHz optical interleaver that uses a
      novel ring cavity architecture. In a 25-GHz channel spacing application the
      interleaver exhibits a 0.5-dB passband larger than 0.14 nm (17.5 GHz), a 25-dB
      stopband greater than 0.14 nm (17.5 GHz), and channel isolation better than 28 dB
      over the entire C band.

PMID- 15943281
TI  - Gap solitons in a model of a hollow optical fiber.
AB  - We introduce a model for two coupled waves propagating in a hollow-core fiber: a
      linear dispersionless core mode and a dispersive nonlinear surface mode. The
      linear coupling between them may open a bandgap through the mechanism of
      avoidance of crossing between dispersion curves. The third-order dispersion of
      the surface mode is necessary for the existence of the gap. Numerical
      investigation reveals that the entire bandgap is filled with solitons, and they
      are stable in direct simulations. The gap-soliton (GS) family includes stable
      pulses moving relative to the given reference frame up to limit values of the
      corresponding boost delta, beyond which they do not exist. The limit values are
      asymmetric for delta > or < 0. Recently observed solitons in hollow-core photonic
      crystal fibers may belong to this GS family.

PMID- 15943282
TI  - Spontaneous decay rates in active waveguides.
AB  - We present a new method of measuring the guided, radiated, and total decay rates
      in uniform waveguides. It is also shown theoretically that large modifications of
      the total decay rate can be achieved in realistic erbium-doped fiber amplifiers
      and erbium-doped waveguide amplifiers with effective mode area radii smaller than
      approximately 1 microm.

PMID- 15943283
TI  - Extended Jones matrix for first-order polarization mode dispersion.
AB  - I present numerical simulations of the average transfer function of polarization
      mode dispersion (PMD) in optical fibers conditioned on various given values of
      the differential group delay (DGD). I find that even fibers with relatively small
      mean DGD can exhibit significant coupling between the two principal states of
      polarization. The average frequency dependence of this coupling can be
      approximated by a generic analytic function that deviates substantially from the
      quadratic frequency dependence that is often assumed in second-order PMD models.
      Finally, I define an extended transfer matrix for first-order PMD that describes
      the average frequency dependence of all PMD-induced distortions as a function of
      the DGD and show that this matrix is much better suited for optical PMD
      compensation than that of a conventional first- and second-order PMD model.

PMID- 15943284
TI  - Development of a multiwavelength Raman fiber laser based on phase-shifted fiber
      Bragg gratings for long-distance remote-sensing applications.
AB  - We propose a simple and flexible multiwavelength Raman fiber laser based on phase
      shifted fiber Bragg gratings (FBGs) and a tunable chirped FBG. Using a simple
      multiwavelength Raman laser configuration with a single phase-shifted FBG and a
      tunable chirped FBG, we readily achieved simultaneous two-channel sensing probes
      with a high extinction ratio of more than 50 dB over a 50-km distance. The
      multiwavelength output was stable and the peak fluctuation was less than 0.5 dB.
      The temperature and strain sensitivities are estimated to be 10.1 pm/degrees C
      and 7.5 pm/microstrain, respectively.

PMID- 15943285
TI  - Fabrication of long-period gratings in poly(methyl methacrylate-co-methyl vinyl
      ketone-co-benzyl methacrylate)-core polymer optical fiber by use of a mercury
      lamp.
AB  - Polymer optical fiber (POF) with a highly photosensitive poly(methyl methacrylate
      co-methyl vinyl ketone-co-benzyl methacrylate) core is fabricated. Gratings can
      be fabricated in the core of a POF with a low-cost mercury lamp. The part of the
      emission spectrum of the mercury lamp in which the cladding material exhibits
      photosensitivity is effectively filtered by a 1.5-mm-thick Pyrex glass to ensure
      that a long-period grating is formed only in the core of a POF. A long-period
      grating with a 3-dR resonant peak at 1568 nm is fabricated with 0.3 mW/cm2 of UV
      irradiation over a period of 200 s.

PMID- 15943286
TI  - Coherence effect on the measurement of optical fiber nonlinear coefficient.
AB  - We investigated a source coherence effect on the measurement of the optical fiber
      nonlinear coefficient by use of dual optical frequencies. We produced coherent
      and incoherent dual optical frequencies with a self-heterodyne Mach-Zehnder
      interferometer with and without a delay line, respectively. Our measurement
      results included both an electrostrictive and a Kerr nonlinear coefficient
      because of the low modulation frequency. Comparing the coherent case with an
      incoherent case, we obtained a nonlinear coefficient that was more than 3% higher
      in the coherent case.

PMID- 15943287
TI  - Leakage of the fundamental mode in photonic crystal fiber tapers.
AB  - We report detailed measurements of the optical properties of tapered photonic
      crystal fibers (PCFs). We observe a striking long-wavelength loss as the fiber
      diameter is reduced, despite the minimal airhole collapse along the taper. We
      associate this loss with a transition of the fundamental core mode as the fiber
      dimensions contract: At wavelengths shorter than this transition wavelength, the
      core mode is strongly confined in the fiber microstructure, whereas at longer
      wavelengths the mode expands beyond the microstructure and couples out to higher
      order modes. These experimental results are discussed in the context of the so
      called fundamental mode cutoff described by Kuhlmey et al. [Opt. Express 10, 1285
      (2002)], which apply to PCFs with a finite microstructure.

PMID- 15943288
TI  - Refractive-index profiling of azimuthally asymmetric optical fibers by
      microinterferometric optical phase tomography.
AB  - Accurate nondestructive refractive-index profiling is needed in the modeling,
      design, and manufacturing of optical fibers and fiber devices. Most profile
      measurement techniques cannot correctly characterize fibers with small or
      irregular refractive-index variations over their cross sections.
      Microinterferometric optical phase tomography (MIOPT) is a technique that allows
      measurement of fiber refractive-index profiles exhibiting such variations. We
      present the first demonstration, to our knowledge, of MIOPT. The profile of a
      polarization-maintaining fiber is measured by MIOPT and shown to be in agreement
      with (destructive) fiber end-face measurements. MIOPT is also applied to the
      limiting case of a symmetric single-mode fiber.

PMID- 15943289
TI  - Recovery of spectral features readout with frequency-chirped laser fields.
AB  - A data-processing technique is proposed for use with conventional frequency
      chirped absorption spectroscopy to ensure accurate mapping of spectral features
      into time-domain signatures with arbitrarily fast readout chirp rates. This
      technique recovers the spectrum from a signal that is distorted owing to the fast
      chirp rate and therefore facilitates fast measurement of the spectral features
      over a broad spectral range with high resolution. Both numerical simulations and
      experimental results are presented.

PMID- 15943290
TI  - One-dimensional optical imaging with a volume holographic optical element.
AB  - We propose a novel imaging structure based on a volume holographic optical
      element that allows one-dimensional optical imaging through a specific Bragg
      window. The lateral magnification is shown to be linear and negative. Lateral
      magnifications of 2.5, 5, and 10 of the imaging element are demonstrated
      theoretically and experimentally.

PMID- 15943291
TI  - Information capacity gain by time-division multiplexing in three-dimensional
      integral imaging.
AB  - We evaluate improvements in information capacity gained by use of time-division
      multiplexing (TDM) in three-dimensional integral imaging (II) systems. This
      analysis supports the motivation for two TDM methods in II [Opt. Lett. 27, 324
      (2002); 1144 (2002)] that we previously developed.

PMID- 15943293
TI  - Short-length microstructured phosphate glass fiber lasers with large mode areas.
AB  - We report fabrication and testing of the first phosphate glass microstructured
      fiber lasers with large Er-Yb-codoped cores. For an 11-cm-long cladding-pumped
      fiber laser, more than 3 W of continuous wave output power is demonstrated, and
      near single-mode beam quality is obtained for an active core area larger than 400
      microm2.

PMID- 15943292
TI  - Optical biosensor with dispersion compensation.
AB  - Dispersion limits performance in many optical systems. In surface plasmon
      resonance (SPR) biosensors, the sensing area is an optical element in which the
      dispersion depends on the effective refractive index of the biochemical compounds
      to be measured. We report a method of compensating for wavelength dispersion in
      SPR biosensors employing two integrated diffractive optical coupling elements in
      a polymer substrate. The dispersion compensation is achieved over the whole
      dynamic measurement range and provides a biosensor more robust to wavelength
      fluctuations than prism-coupler SPR systems. The concept can readily be employed
      in other types of sensor measuring refractive-index changes.

PMID- 15943294
TI  - Efficient femtosecond green-light source with a diode-pumped mode-locked
      Yb3+:KY(WO4)2 laser.
AB  - Efficient generation of femtosecond pulses at 524 nm is demonstrated by the
      extracavity frequency doubling of the output of a diode-pumped femtosecond
      Yb3+:KY(WO4)2 laser using a periodically poled LiTaO3 crystal. An average second
      harmonic power of 120 mW is produced at an internal conversion efficiency of 40%.
      The temporal characteristics of the frequency-doubled pulses as a function of
      focusing conditions in a thick nonlinear crystal are investigated experimentally,
      and pulses as short as 225 fs are generated at a pulse repetition frequency of 86
      MHz.

PMID- 15943295
TI  - Self-injection locking of an extraordinarily wide broad-area diode laser with a
      1000-microm-wide emitter.
AB  - The experimental results of self-injection locking of an antireflection-coated
      broad-area diode laser with a 1000-microm-wide emitting area are presented. To
      our knowledge, it is the broadest single-element diode laser that has been used
      in an external-feedback cavity until now. Usually, wide diode lasers suffer from
      filamentation, which leads to poor spatial beam quality. We show, however, that
      the beam quality of the diode laser is improved significantly when we use
      asymmetric self-injection locking. An output power of 2.05 W is obtained with a
      beam quality factor M2 of 2.7. The self-injection locking technique improves the
      beam quality by a factor of 107. By comparing the results with those obtained
      with an ordinarily coated diode laser with a 1000-microm-wide emitter we show
      that antireflection coating on the front facet is decisive for this improvement
      in the beam quality.

PMID- 15943296
TI  - Femtosecond pulse generation with a diode-pumped Yb3+:YVO4 laser.
AB  - A diode-pumped Yb:YVO4 laser has been passively mode locked for the first time,
      to our knowledge. 120 fs pulses with an average output power of 300 mW and a peak
      power as high as 14.5 kW are obtained by use of a semiconductor saturable
      absorber mirror for passive mode locking. The optical spectrum has a 10 nm
      bandwidth (full width at half-maximum) and is centered at 1021 nm.

PMID- 15943297
TI  - Power-insensitive side locking for laser frequency stabilization.
AB  - We present a simple modification of the traditional method of locking the laser
      frequency to the side of an atomic spectral line. We achieve first-order power
      insensitivity at arbitrary intensity and frequency and in this way eliminate one
      of the major drawbacks of the traditional method. A similar approach could also
      be used in locking a laser to a Fabry-Perot cavity.

PMID- 15943298
TI  - Raman band intensities of tellurite glasses.
AB  - Raman spectra of TeO2-based glasses doped with WO3, ZnO, GeO2, TiO2, MoO3, and
      Sb2O3 are measured. The intensity of bands in the Raman spectra of MoO3-TeO2 and
      MoO3-WO3-TeO2 glasses is shown to be 80-95 times higher than that for silica
      glass. It is shown that these glasses can be considered as one of the most
      promising materials for Raman fiber amplifiers.

PMID- 15943299
TI  - Backscattering target detection in a turbid medium by use of circularly and
      linearly polarized light.
AB  - The polarization properties of the backscattered light from a turbid medium
      containing large-diameter (10.143-microm) and small-diameter (0.202-microm)
      spherical polystyrene particles are studied. It is shown that the difference in
      the polarization properties of the emerging light that originates at the target
      and that is backscattered from the medium allows for improvement of image
      contrast by use of polarized light. Based on the images obtained by the CCD
      camera, the polarization memory effect with circularly polarized light is
      demonstrated to have an advantage over the linear polarization technique in
      imaging a highly reflective target inside a turbid medium containing large
      particles.

PMID- 15943300
TI  - Terahertz pulse generation via optical rectification in photonic crystal
      microcavities.
AB  - Using a three-dimensional fully vectorial nonlinear time-domain analysis, we
      numerically investigate generation of terahertz radiation by pumping a photonic
      crystal microcavity out of resonance. High quality factors and a quadratic
      susceptibility lead to few-cycle terahertz pulses via optical rectification.
      Material dispersion as well as linear and nonlinear anisotropy is fully accounted
      for.

PMID- 15943301
TI  - Experimental investigation of amplitude and phase quantum correlations in a type
      II optical parametric oscillator above threshold: from nondegenerate to
      degenerate operation.
AB  - We describe a stable type II optical parametric oscillator operated above
      threshold that provides 9.7 +/- 0.5 dB (89%) of quantum noise reduction on the
      intensity difference of the signal and idler modes. We also report the first
      experimental study, to our knowledge, by homodyne detection of the generated
      bright two-mode state in the case of frequency-degenerate operation obtained by
      the introduction of a birefringent plate inside an optical cavity.

PMID- 15943302
TI  - Reconfigurable directional couplers and junctions optically induced by
      nondiffracting Bessel beams.
AB  - We put forward the concept of reconfigurable structures optically induced by
      mutually incoherent nondiffracting Bessel beams in Kerr-type nonlinear media. We
      address collinear couplers and X junctions and show how one can tune the
      switching properties of such structures by varying the intensity of the Bessel
      beams.

PMID- 15943303
TI  - Input-output relations for a three-port grating coupled Fabry-Perot cavity.
AB  - We analyze an optical three-port reflection grating by means of a scattering
      matrix formalism. Amplitude and phase relations among the three ports, i.e., the
      three orders of diffraction, are derived. Such a grating can be used as an all
      reflective, low-loss coupler to Fabry-Perot cavities. We derive the input-output
      relations of a three-port grating coupled cavity and find distinct properties
      that are not present in two-port coupled cavities. The cavity relations further
      reveal that the three-port coupler can be designed such that the additional
      cavity port interferes destructively. In this case the all-reflective, low-loss,
      single-end Fabry-Perot cavity becomes equivalent to a standard transmissive, two
      port coupled cavity.

PMID- 15943304
TI  - Plasmonic subwavelength waveguides: next to zero losses at sharp bends.
AB  - We demonstrate that approximately 100% transmission of a strongly localized
      channel plasmon polariton can be achieved through a sharp 90 degrees bend in a
      subwavelength waveguide in the form of a triangular groove on a metal surface--a
      feature that has previously been demonstrated only for photonic crystal
      waveguides, which do not provide subwavelength localization. Conditions for
      minimum reflection and radiative losses at the bend are investigated numerically
      by the finite-difference time-domain algorithm. Dissipation in the structure is
      demonstrated to be sufficiently low to ensure significant propagation distances
      (a number of wavelengths) of the localized plasmon in each of the arms of the
      bend.

PMID- 15943305
TI  - Left-handed media and homogenization of photonic crystals.
AB  - Using homogenization theory, we derive the effective permittivity and
      permeability of a wire-mesh photonic crystal from first principles. We show that
      this structure does not lead to a left-handed medium when it is embedded in a
      matrix with a negative mu, but that resonators in a medium with a negative
      epsilon do form a left-handed medium in the correct range of frequencies.

PMID- 15943306
TI  - Efficient polarization squeezing in optical fibers.
AB  - We report on a novel and efficient source of polarization squeezing that uses a
      single pass through an optical fiber. Using the fiber's two orthogonal
      polarization axes produces two identical squeezed beams. Combining these in a
      Stokes measurement generates polarization squeezing of up to 5.1 +/- 0.3 dB.
      Furthermore, this scheme enables us to directly measure, for both polarizations,
      the noise of any given quadrature.

PMID- 15943307
TI  - Quantum noise measurements in a continuous-wave laser-diode-pumped Nd:YAG
      saturated amplifier.
AB  - We present measurements of the power noise due to optical amplification in a
      Nd:YAG free-space traveling-wave amplifier as the amplifier transitions from the
      linear regime into the heavily saturated regime. The quantum noise behavior is
      demonstrated by saturating the gain of a 100-W class zigzag slab amplifier with a
      high-power beam and measuring the power noise detected by a single-spatial-mode
      probe beam traversing the same optical path through the amplifier.

PMID- 15943308
TI  - Optical selectivity in optically dense media driven by optimized Gaussian-type
      ultrashort pulse pairs.
AB  - We theoretically demonstrate that selective resonant excitation can be achieved
      in a dense collection of V-type three-level atoms by optimizing the pulse delay
      and peak intensity ratio of an applied phase-tailored ultrashort pulse pair. Near
      dipole-dipole interaction plays an important role in the quantum control of
      selective excitations since it brings about an intrinsic frequency shift in the
      atomic resonance, which builds up various excitation pathways. As a consequence,
      we can control the quantum interference between various pathways by shaping the
      excitation pulse pair to steer the atomic excitation selectively toward a desired
      quantum state.

PMID- 15943309
TI  - Storage and long-distance distribution of telecommunications-band polarization
      entanglement generated in an optical fiber.
AB  - We demonstrate storage of polarization-entangled photons for 125 micros, a record
      storage time to date, in a 25-km-long fiber spool, using a telecommunications
      band fiber-based source of entanglement. With this source we also demonstrate
      distribution of polarization entanglement over 50 km by separating the two
      photons of an entangled pair and transmitting them individually over separate 25
      km fibers. The measured two-photon fringe visibilities were 82% in the storage
      experiment and 86% in the distribution experiment. Preservation of polarization
      entanglement over such long-distance transmission demonstrates the viability of
      all-fiber sources for use in quantum memories and quantum logic gates.

PMID- 15943310
TI  - Perfect corner reflector.
AB  - We numerically investigate the electromagnetic field radiated by a line source
      within a perfect lens [Phys. Rev. Lett. 85, 3966 (2000)] consisting of two
      orthogonal planes delimiting positive and negative index media. Use of a
      coordinate transformation [J. Phys. Condens Matter 15, 6345 (2003)] together with
      a well-adapted transfer-matrix method permits rigorous calculation of the vector
      field. We find that two negative corners combine to make a cavity that traps
      light along closed trajectories. Finally, we numerically show that the field
      presents some spatial oscillations with a period that is proportional to
      absorption sigma inside the negative materials as 1/ln sigma and that it is
      associated with an infinite density of states when sigma tends toward 0.

PMID- 15943311
TI  - Wigner representation and geometric transformations of optical orbital angular
      momentum spatial modes.
AB  - An exact Wigner representation of optical spatial modes carrying orbital angular
      momentum is found in closed form by exploiting the underlying SU(2) Lie-group
      algebra of their associated Poincare sphere. Orthogonality relations and
      observables of these states are obtained within the phase space picture.
      Development of geometric phases on mode transformations is also elucidated.

PMID- 15943312
TI  - Effect of a thin dielectric layer on terahertz transmission characteristics for
      metal hole arrays.
AB  - We studied the role of surface-plasmon polaritons (SPPs) in a bandpass
      transmission property of two-dimensional metal hole arrays (2D-MHAs) by
      investigating the effect of thin dielectric layers on the 2D-MHA surfaces. We
      measured zero-order transmission spectra of the 2D-MHAs by changing the thickness
      of the dielectric layer and found that the bandpass transmission peak shifted to
      the lower-frequency side with increasing layer thickness, owing to the change of
      the resonant frequency of the SPP. This result shows that SPPs play a crucial
      role in the transmission property of 2D-MHAs in the terahertz region.

PMID- 15943313
TI  - Faraday rotation in a two-dimensional photonic crystal with a magneto-optic
      defect.
AB  - We study the magneto-optic (MO) Faraday rotation in a two-dimensional square
      lattice photonic crystal with a central MO defect layer in the optical wavelength
      range. We show that when a TM plane wave is incident upon a photonic crystal, an
      enhancement of Faraday rotation takes place in a region where a resonance peak
      appears in the photonic bandgap. In this region the mode conversion is high.

PMID- 15943314
TI  - Structure for localizing electromagnetic waves with a left-handed-medium slab and
      a conducting plane.
AB  - A new structure is proposed for localizing electromagnetic waves and energies
      with a left-handed-medium (LHM) slab and a perfectly electrically conducting
      (PEC) plane. When a current source is placed in front of a perfectly matched LHM
      slab with negative permittivity -epsilon0 and negative permeability -mu0 and a
      PEC plane is placed at the image point, we show rigorously that all the
      electromagnetic waves are confined in a region between the source and the PEC
      plane, and the fields outside the region are completely zero. Such an energy
      localization system would be useful in medical treatments that use concentrated
      optical and microwave energies. However, a perfectly matched LHM is unphysical
      and does not exist in nature. Hence we further study the loss and retardation
      effects of LHM on the energy localization. Numerical results are presented for
      the lossy LHM structure to demonstrate the energy localization.

PMID- 15943315
TI  - Pump-probe differencing technique for cavity-enhanced, noise-canceling saturation
      laser spectroscopy.
AB  - We present an experimental technique that permits mechanical-noise-free, cavity
      enhanced frequency measurements of an atomic transition and its hyperfine
      structure. We employ the 532-nm frequency-doubled output from a Nd:YAG laser and
      an iodine vapor cell. The cell is placed in a folded ring cavity (FRC) with
      counterpropagating pump and probe beams. The FRC is locked with the Pound-Drever
      Hall technique. Mechanical noise is rejected by differencing the pump and probe
      signals. In addition, this differenced error signal provides a sensitive measure
      of differential nonlinearity within the FRC.

PMID- 15943316
TI  - Measurement of Fourier-synthesized optical waveforms.
AB  - Following the experiments of Shverdin and colleagues [Phys. Rev. Lett. 94, 033904
      (2005)], we describe a technique for determining the temporal envelope of an
      optical beam whose spectrum consists of n discrete, equally spaced frequency
      components. Four-wave mixing is employed to generate n-1 higher-frequency
      sidebands. The relative intensities of these sidebands, together with the
      intensities of the incident side-bands, determine the unknown relative phases of
      the incident beam.

PMID- 15943317
TI  - Remote transfer of a high-stability and ultralow-jitter timing signal.
AB  - Transfer of a high-stability and ultralow-jitter timing signal through a fiber
      network via a mode-locked fiber laser is demonstrated. With active cancellation
      of the fiber-transmission noise, the fractional instability for transfer of a
      radio-frequency signal through a 6.9- (4.5-) km round-trip installed (laboratory
      based) fiber network is below 9(7) x 10(-15) tau(-1/2) for an averaging time tau
      > or = 1 s, limited by the noise floor of the frequency-counting system. The
      noise cancellation reduces the rms timing jitter, integrated over a bandwidth
      from 1 Hz to 100 kHz, to 37 (20) fs for the installed (laboratory-based) fiber
      network, representing what is to our knowledge the lowest reported jitter for
      transfer of a timing signal over kilometer-scale distances using an installed
      (laboratory-based) optical-fiber network.

PMID- 15943318
TI  - Ultralow-noise mode-locked laser with coupled optoelectronic oscillator
      configuration.
AB  - We describe simultaneous generation of ultralow-noise optical pulses and
      microwave signal with a mode-locked fiber laser in a coupled optoelectronic
      oscillator configuration. We demonstrate 9.2-GHz optical and microwave signals
      with the measured phase noise of -140 dBc/Hz at 10-kHz offset frequency. We show
      that the mode-locked laser in the photonic oscillator serves as a high-Q filter
      and is responsible for the observed low phase noise.

PMID- 15943319
TI  - Broadly tunable femtosecond parametric oscillator using a photonic crystal fiber.
AB  - Pulses as short as 460 fs and a tuning range as wide as 200 nm around 1 microm
      have been achieved from a photonic-crystal-fiber-based parametric oscillator. The
      ring cavity with only 65 cm of photonic crystal fiber is synchronously pumped
      with a tunable passively mode-locked Yb-doped fiber laser. Widely extended
      tunability is achieved by using the modulation instability gain in normal
      dispersion as the result of high-order dispersion in the photonic crystal fiber.

PMID- 15943320
TI  - Regularized phase tracker with isophase scanning strategy for analysis of dynamic
      interferograms of nonwetting droplets under excitation.
AB  - The surface of a nonwetting droplet is separated from a solid surface by a
      continuous supply of a lubricating gas film within the apparent contact region.
      Under certain conditions, e.g., application of an external excitation force, the
      gas film thickness can decrease to a level where intermolecular forces cause the
      droplet to wet the surface. The thickness of the lubricating film can be measured
      by interferometry. Externally imposed oscillations change the shape of the film,
      leading to dynamic interference fringes that are recorded with a high-speed CCD
      camera. We propose a spatiotemporal analysis of the interference patterns based
      on the regularized phase-tracker method. This well-known method minimizes a cost
      function to estimate the absolute phase of a single element in the interferogram.
      A proper scanning method along all elements of the interferogram is necessary to
      avoid phase estimation errors that will propagate throughout the entire
      continuous phase image of interest. The scanning method we propose traces along
      contours of constant phase in the interferogram and does not require segmentation
      of the interferogram in dark and bright fringes. Results in the form of dynamic
      height profiles of droplets under excitation obtained by this method are
      presented.

PMID- 15943321
TI  - Wave-front analysis method of circular aperture sampling for collimation testing.
AB  - A new type of wave-front analysis method for the collimation testing of laser
      beams is proposed. A concept of wave-front height is defined, and, on this basis,
      the wave-front analysis method of circular aperture sampling is introduced. The
      wave-front height of the tested noncollimated wave can be estimated from the
      distance between two identical fiducial diffraction planes of the sampled wave,
      and then the divergence is determined. The design is detailed, and the experiment
      is demonstrated. The principle and experiment results of the method are
      presented. Owing to the simplicity of the method and its low cost, it is a
      promising method for checking the collimation of a laser beam with a large
      divergence.

PMID- 15943322
TI  - Optimal transformations for optical multiplex measurements in the presence of
      photon noise.
AB  - Hadamard multiplexing is a measurement strategy that yields best sensitivity
      improvements over scanning measurements for signal-independent detector noise.
      The presence of photon noise degrades the performance of Hadamard multiplexing
      because of the increase of photon noise by the superposition of multiple signals.
      I derive the reduction of the sensitivity gain of a Hadamard measurement and an
      upper limit for the gain of any cyclic multiplexing strategy in the presence of
      photon noise. This upper limit clearly exceeds the reduced Hadamard gain and can
      be achieved by multiplexing sequences that differ from Hadamard S sequences but
      also share some similarities with respect to their autocorrelation. Examples of
      such sequences are given. As the analysis shows, the presence of photon noise
      limits the gain of multiplexing strategies to a finite value, which depends on
      the ratio between photon noise and detector noise and cannot be exceeded by
      increasing the number of multiplexed channels. In addition, only switching
      multiplex schemes, which superpose either all the light or no light of individual
      channels, can achieve the upper limit of the gain.

PMID- 15943323
TI  - Magnitude and direction of motion with speckle correlation and the optical
      fractional Fourier transform.
AB  - The optical fractional Fourier transform (OFRT) in combination with speckle
      photography has previously been used to measure the magnitude of surface tilting
      and translation. Previous OFRT techniques used to determine motion have not been
      able to discern the direction of the tilt and translation. A simple new approach
      involving use of correlation is presented to overcome this limitation. Controlled
      variation of the minimum resolution and dynamical range of measurement is
      demonstrated. It is then experimentally confirmed that if a rigid body's motion
      is captured by two OFRT systems of different orders, the direction and magnitude
      of both the tilting and the in-plane translation motion of the body can be
      independently determined without a priori knowledge. The experimental results
      confirm the validity of previous theoretical predictions.

PMID- 15943324
TI  - Local denoising of digital speckle pattern interferometry fringes by
      multiplicative correlation and weighted smoothing splines.
AB  - We evaluate the use of smoothing splines with a weighted roughness measure for
      local denoising of the correlation fringes produced in digital speckle pattern
      interferometry. In particular, we also evaluate the performance of the
      multiplicative correlation operation between two speckle patterns that is
      proposed as an alternative procedure to generate the correlation fringes. It is
      shown that the application of a normalization algorithm to the smoothed
      correlation fringes reduces the excessive bias generated in the previous
      filtering stage. The evaluation is carried out by use of computer-simulated
      fringes that are generated for different average speckle sizes and intensities of
      the reference beam, including decorrelation effects. A comparison with filtering
      methods based on the continuous wavelet transform is also presented. Finally, the
      performance of the smoothing method in processing experimental data is
      illustrated.

PMID- 15943325
TI  - Miniature fiber-optic pressure sensor with a polymer diaphragm.
AB  - The fabrication and experimental investigation of a miniature optical fiber
      pressure sensor for biomedical and industrial applications are described. The
      sensor measures only 125 microm in diameter. The essential element is a thin
      polymer diaphragm that is positioned inside the hollow end of an optical fiber.
      The cavity at the fiber end is made by a simple and effective micromachining
      process based on wet etching in diluted HF acid. Thus a Fabry-Perot
      interferometer is formed between the inner fiber-cavity interface and the
      diaphragm. The fabrication technique is described in detail. Different sensor
      prototypes were fabricated upon 125 microm-diameter optical fiber that
      demonstrated pressure ranges from 0 to 40 and from 0 to 1200 kPa. A resolution of
      less than 10 Pa was demonstrated in practice. The fabrication technique presented
      facilitates production of simple and low-cost disposable pressure sensors by use
      of materials with that ensure the required biocompatibility.

PMID- 15943326
TI  - Directional and angle-resolved optical scattering of high-performance translucent
      polymer sheets for energy-efficient lighting and skylights.
AB  - Transparent refractive-index matched micro (TRIMM) particles have proved to be an
      excellent scattering component for use in translucent sheets. Measurements of
      hemispheric transmittance and reflectance versus angle of incidence, as well as
      angle-resolved studies of such translucent sheets, have been carried out to
      complement earlier published hemispheric reflectance and transmittance spectral
      measurements carried out at normal angle of incidence. Hemispheric values
      relative to angle of incidence are of interest for daylighting applications and
      building simulations, and angle-resolved measurements are vital for verifying
      that our modeling tools are reliable. Ray-tracing simulations based on Mie
      scattering for the individual TRIMM particles and angle-resolved measurements are
      in good agreement, indicating that the simulation method used is practical for
      the design of new scattering profiles by varying particle concentration or
      refractive index.

PMID- 15943327
TI  - Folded catadioptric panoramic lens with an equidistance projection scheme.
AB  - A new formula for a catadioptric panoramic lens with an equidistance projection
      scheme has been derived. The fabricated lens has a field of view that is wider
      than that of any previously reported panoramic lens, and the nonimaged region
      near the back of the camera has a constant volume with zero angular extension.

PMID- 15943328
TI  - Far-field pattern simulation of flip-chip bonded power light-emitting diodes by a
      Monte Carlo photon-tracing method.
AB  - The far-field pattern of light-emitting diodes (LEDs) is an important issue in
      practical applications. We used a Monte Carlo photon-tracing method for the
      package design of flip-chip bonded power LEDs. As a first-order approximation, we
      propose using a plane light source model to calculate the far-field pattern of
      encapsulated LEDs. The far-field pattern is also studied by use of a more
      detailed model, which takes the structure of all epitaxial layers of a flip-chip
      bonded power LED into consideration. By comparing the simulation results with the
      experimental data, we have concluded that the plane light source model is much
      less time-consuming and offers fairly good precision for package design.

PMID- 15943329
TI  - Adaptive correction to the speckle correlation fringes by using a twisted-nematic
      liquid-crystal display.
AB  - An innovative technique for reducing speckle noise and improving the intensity
      profile of the speckle correlation fringes is presented. The method is based on
      reducing the range of the modulation intensity values of the speckle interference
      pattern. After the fringe pattern is corrected adaptively at each pixel, a simple
      morphological filtering of the fringes is sufficient to obtain smoothed fringes.
      The concept is presented both analytically and by simulation by using computer
      generated speckle patterns. The experimental verification is performed by using
      an amplitude-only spatial light modulator (SLM) in a conventional electronic
      speckle pattern interferometry setup. The optical arrangement for tuning a
      commercially available LCD array for amplitude-only behavior is described. The
      method of feedback to the LCD SLM to modulate the intensity of the reference beam
      in order to reduce the modulation intensity values is explained, and the
      resulting fringe pattern and increase in the signal-to-noise ratio are discussed.

PMID- 15943330
TI  - Optimization of distributed resistive metal film heaters in thermally tunable
      dispersion compensators for high-bit-rate communication systems.
AB  - Tunable dispersion compensators are an essential component for optical networks
      operating at 40 Gbits/s and beyond. One fiber-based tunable dispersion
      compensator that has proved to be effective consists of a chirped fiber Bragg
      grating tuned by a thin-film distributed resistive heating element. We describe
      several modifications to the heater design that minimize temperature-induced
      higher-order dispersion, eliminate the need for a second stabilization heater
      when the device is operated at constant ambient temperature, and significantly
      lower its maximum operating temperature. We demonstrate a tunable dispersion
      compensator with a single thin-film heater that provides over 500 ps/nm of
      tunable dispersion over a fixed 100-GHz bandwidth with a maximum operating
      temperature of less than 125 degrees C above ambient.

PMID- 15943331
TI  - Experimental realization of an imaging system with an extended depth of field.
AB  - We describe the experimental realization of an all-optical imaging system with an
      extended depth of field (DOF). The core of the system is a phase mask consisting
      of 16 Fresnel lenses (FLs) that are spatially multiplexed and mutually exclusive.
      Because each FL, in tandem with the primary lens, is designed to produce a sharp
      image for a specific object plane location, jointly the FLs achieve a wide DOF.
      However, the resultant image exhibits reduced resolution. The acquired image,
      onto which we did not apply any postprocessing, clearly is sharper than that
      acquired with a clear-aperture imaging system with the same pupil size.

PMID- 15943332
TI  - Data compression for speckle correlation interferometry temporal fringe pattern
      analysis.
AB  - Temporal fringe pattern analysis is gaining prominence in speckle correlation
      interferometry, in particular for transient phenomena studies. This form of
      analysis, nevertheless, necessitates large data storage. Current compression
      schemes do not facilitate efficient data retrieval and may even result in
      important data loss. We describe a novel compression scheme that does not result
      in crucial data loss and allows for the efficient retrieval of data for temporal
      fringe analysis. In sample tests with digital speckle interferometry on fringe
      patterns of a plate and of a cantilever beam subjected to temporal phase and load
      evolution, respectively, we achieved a compression ratio of 1.6 without filtering
      out any data from discontinuous and low fringe modulation spatial points. By
      eliminating 38% of the data from discontinuous and low fringe modulation spatial
      points, we attained a significant compression ratio of 2.4.

PMID- 15943333
TI  - Near-field nonuniformities in angularly multiplexed KrF fusion lasers with
      induced spatial incoherence.
AB  - Induced spatial incoherence (ISI) has been proposed for KrF laser drivers to
      achieve the high degree of spatial beam uniformity required for direct-drive
      inertial confinement fusion. Although ISI provides ultrasmooth illumination at
      the far field of the laser, where the target is located, it can still allow the
      beams in the quasi-near field to develop a time-averaged spatial structure. This
      speckle, which arises primarily from random-phase aberration, builds up as the
      laser beams propagate away from the pupil plane located at the final amplifier
      stage; it is distinct from any structure imposed by gain nonuniformities in the
      amplifiers. Because of the spatial incoherence, the speckle is significantly
      smaller than that experienced by coherent beams. Nevertheless, it remains a
      damage issue, especially for the long beam delay paths required in angularly
      multiplexed KrF lasers. We develop a novel algorithm for calculating the time
      integrated intensities; compare simulations and measurements of the near-field
      speckle in the Nike KrF laser; and explore options, such as aberration reduction
      and optical relaying, for controlling the problem in future angularly multiplexed
      KrF drivers.

PMID- 15943334
TI  - Submicrosecond temperature measurement in liquid water with laser-induced thermal
      acoustics.
AB  - Using laser-induced thermal acoustics, we demonstrate nonintrusive and remote
      sound-speed and temperature measurements in liquid water. Unsteady thermal
      gradients in the water sample produce fast, random laser beam misalignments,
      which are the primary source of uncertainty in these measurements. For water
      temperatures over the range 10 degrees C to 45 degrees C, the precision of a
      single 300-ns-duration measurement varies from +/-1 to +/-16.5 m/s for sound
      speed and from +/-0.3 degrees C to +/-9.5 degrees C for temperature. Averaging
      over 10 s (100 laser pulses) yields accuracies of +/-0.64 m/s and +/-0.45 degrees
      C for sound speed and temperature, respectively.

PMID- 15943335
TI  - Characterization of a multiwavelength Brillouin-erbium fiber laser based on a
      linear cavity configuration.
AB  - We experimentally demonstrate a simple method for generating a multiwavelength
      Brillouin comb by utilizing a linear cavity of hybrid Brillouin-erbium fiber
      lasers (BEFLs). The optimization of Brillouin pump wavelength, power, and erbium
      gain played a significant role in determining the maximum number of Brillouin
      Stokes signals generated. Simultaneous and stable multiple-wavelength laser
      output of 22 lines with 10.88-GHz channel spacing has been obtained with good
      flatness. Various parameters such as 980-nm pump power, Brillouin pump
      wavelength, and Brillouin pump power that affect the performance of a
      multiwavelength BEFL system have been investigated. An analysis of the tuning
      range of the system is presented.

PMID- 15943336
TI  - Three-dimensional analysis of mode discrimination in vertical-cavity surface
      emitting lasers.
AB  - Optical mode discrimination in vertical-cavity surface-emitting lasers that
      contain distributed Bragg reflectors (DBRs) and a spatially limited gain medium
      is analyzed numerically. It is assumed that the output field is linearly
      polarized owing to gain selectivity. The analysis employs a three-dimensional
      model and an angular spectrum of plane-wave decomposition with the proper
      polarizations. Two types of round aperture are considered, namely, a Gaussian
      aperture and a ring-peak aperture that represents gain saturation. Coupled with
      the DBRs, the former aperture yields nearly Laguerre-Gaussian modes, whereas the
      latter aperture significantly distorts the mode shapes. In both cases, narrowband
      DBRs provide the best mode discrimination.

PMID- 15943337
TI  - Nonlinear optical absorption of ZnO doped with copper nanoparticles in the
      picosecond and nanosecond pulse laser field.
AB  - The nonlinear absorption of nanocomposite layers based on ZnO implanted with Cu+
      ions with an energy of 160 keV in implantation doses of 10(16) and 10(17)
      ions/cm2 was investigated. The values of the nonlinear absorption coefficient
      were measured by the Z-scan method at a wavelength of 532 nm by use of nanosecond
      and picosecond laser pulses. Possible optical applications of these materials are
      discussed.

PMID- 15943338
TI  - Ground-based zenith sky abundances and in situ gas cross sections for ozone and
      nitrogen dioxide with the Earth Observing System Aura Ozone Monitoring
      Instrument.
AB  - High-accuracy spectral-slit-function calibration measurements, in situ ambient
      absorption gas cell measurements for ozone and nitrogen dioxide, and ground-based
      zenith sky measurements with the Earth Observing System Aura Ozone Monitoring
      Instrument (OMI) flight instrument are reported and the results discussed. For
      use of high-spectral-resolution gas absorption cross sections from the literature
      in trace gas retrieval algorithms, accurate determination of the instrument's
      spectral slit function is essential. Ground-based measurements of the zenith sky
      provide a geophysical determination of atmospheric trace gas abundances. When
      compared with other measurements, they can be used to verify the performance of
      the OMI flight instrument. We show that the approach of using published high
      resolution absolute absorption cross sections convolved with accurately
      calibrated spectral slit functions for OMI compares well with in situ gas
      absorption cell measurements made with the flight instrument and that use of
      these convolved cross sections works well for reduction of zenith sky data taken
      with the OMI flight instrument for ozone and nitrogen dioxide that are retrieved
      from measured spectra of the zenith sky with the differential optical absorption
      spectroscopy technique, the same method to be used for the generation of in
      flight data products. Finally, it is demonstrated that the spectral stability and
      signal-to-noise ratio performance of the OMI flight instrument, as determined
      from preflight component and full instrument tests, are sufficient to meet OMI
      mission objectives.

PMID- 15943339
TI  - Chlorophyll biomass in the global oceans: airborne lidar retrieval using
      fluorescence of both chlorophyll and chromophoric dissolved organic matter.
AB  - For three decades airborne laser-induced fluorescence has demonstrated value for
      chlorophyll biomass retrieval in wide-area oceanic field experiments, satellite
      validation, and algorithm development. A new chlorophyll biomass retrieval theory
      is developed using laser-induced and water Raman normalized fluorescence of both
      (a) chlorophyll and (b) chromophoric dissolved organic matter (CDOM). This
      airborne lidar retrieval theory is then independently confirmed by chlorophyll
      biomass obtained from concurrent (1) ship-cruise retrievals, (2) satellite
      inherent optical property (IOP) biomass retrievals, and (3) satellite standard
      band-ratio chlorophyll biomass retrievals. The new airborne lidar chlorophyll and
      CDOM fluorescence-based chlorophyll biomass retrieval is found to be more robust
      than prior lidar methods that used chlorophyll fluorescence only. Future research
      is recommended to further explain the underlying influence of CDOM on chlorophyll
      production.

PMID- 15943340
TI  - Assessment of the ultraviolet radiation field in ocean waters from space-based
      measurements and full radiative-transfer calculations.
AB  - Quantitative assessment of the UV effects on aquatic ecosystems requires an
      estimate of the in-water radiation field. Actual ocean UV reflectances are needed
      for improving the total ozone retrievals from the total ozone mapping
      spectrometer (TOMS) and the ozone monitoring instrument (OMI) flown on NASA's
      Aura satellite. The estimate of underwater UV radiation can be done on the basis
      of measurements from the TOMS/OMI and full models of radiative transfer (RT) in
      the atmosphere-ocean system. The Hydrolight code, modified for extension to the
      UV, is used for the generation of look-up tables for in-water irradiances. A look
      up table for surface radiances generated with a full RT code is input for the
      Hydrolight simulations. A model of seawater inherent optical properties (IOPs) is
      an extension of the Case 1 water model to the UV. A new element of the IOP model
      is parameterization of particulate matter absorption based on recent in situ
      data. A chlorophyll product from ocean color sensors is input for the IOP model.
      Verification of the in-water computational scheme shows that the calculated
      diffuse attenuation coefficient Kd is in good agreement with the measured Kd.

PMID- 15943341
TI  - Breadboard of a Fourier-transform spectrometer for the radiation explorer in the
      far infrared atmospheric mission.
AB  - In preparation for a possible space mission, a breadboard version named REFIR-BB
      of the Radiation Explorer in the Far Infrared (REFIR) instrument has been built.
      The REFIR is a Fourier-transform spectrometer with a new optical layout operating
      in the spectral range 100-1100 cm(-1) with a resolution of 0.5 cm(-1), a 7-s
      acquisition time, and a signal-to-noise ratio of better than 100. Its mission is
      the spectral measurement in the far infrared of the Earth's outgoing emission,
      with particular attention to the long-wavelength spectral region, which is not
      covered by either current or planned space missions. This measurement is of great
      importance for deriving an accurate estimate of the radiation budget in both
      clear and cloudy conditions. The REFIR-BB permits the trade-off among all
      instrument parameters to be studied, the optical layout to be tested, and the
      data-acquisition strategy to be optimized. The breadboard could be used for high
      altitude ground-based campaigns or could be flown for test flights on aircraft or
      balloon stratospheric platforms. The breadboard's design and the experimental
      results are described, with particular attention to the acquisition strategy and
      characterization of the interferometer. Tests were performed both in laboratory
      conditions and in vacuum. Notwithstanding a loss of efficiency above 700 cm(-1)
      caused by the poor performance of the photolithographic polarizers used as beam
      splitters, the results demonstrate the feasibility of using the spectrometer for
      space applications.

PMID- 15943342
TI  - Geometric determination of saturation in fluorescence spectroscopy.
AB  - In laser spectroscopy, saturation of atomic or molecular transitions cannot be
      ignored, even at modest laser intensities. The saturation status is customarily
      diagnosed from measurements of saturation curves describing the dependence of
      spectroscopic signals on laser intensity. I propose an alternative method that
      relies on a geometric comparison of the spatial laser profile with images of the
      spectroscopic quantity under investigation. A single image can be used to
      determine the saturation status and its associated saturation laser intensity.

PMID- 15943343
TI  - Real-time trace-level detection of carbon dioxide and ethylene in car exhaust
      gases.
AB  - A direct-absorption spectrometer, based on a pulsed, distributed feedback,
      quantum cascade laser with a 10.26-microm wavelength and an astigmatic Herriott
      cell with a 66-m path length, has been developed for high-resolution IR
      spectroscopy. This spectrometer utilizes the intrapulse method, an example of
      sweep integration, in which the almost linear wavelength up-chirp obtained from a
      distributed feedback, quantum cascade laser yields a spectral microwindow of as
      many as 2.5 wave numbers/cm(-1). Within this spectral microwindow, molecular
      fingerprints can be monitored and recorded in real time. This system allows both
      the detection of carbon dioxide and ethylene and the real-time observation of the
      evolution of these gases in the exhaust by-products from several cars.

PMID- 15943344
TI  - Generation of picosecond pulses at five close wavelengths by use of a self-seeded
      Fabry-Perot laser diode and a spectrum-split fiber Bragg grating.
AB  - We have demonstrated simultaneous generation of stable picosecond laser pulses at
      five close wavelengths at a pulse repetition rate of approximately 2 GHz by using
      a self-seeding configuration that consisted of a gain-switched Fabry-Perot laser
      diode (FPLD) with an external cavity formed by a tunable spectrum-split fiber
      Bragg grating (FBG). The FBG selected only one of the modes of the FPLD and, at
      the same time, filtered the selected FPLD mode such that the reflection from the
      FBG, tapped with a directional coupler, provided an output of dual-wavelength
      pulses and the transmission through the FBG provided an output of three
      wavelength pulses. We could change the intensities and the wavelength separations
      of the pulses by adjusting the modulating radio frequency and the temperature of
      the FPLD and the separation of the FBG reflection peaks. In our experiments the
      highest side-mode suppression ratios of the pulses obtained were 44.5 dB for the
      dual-wavelength output and 25.0 dB for the three-wavelength output. Also, the
      laser was demonstrated to minimize pulse intensity imbalance and produce equally
      separated wavelengths (with a wavelength separation of 0.2 nm). This simple laser
      offers considerable flexibility for various applications.

PMID- 15943345
TI  - [Effects of artificial tending on Pinus tabulaeformis forest growth and its
      structural characteristics].
AB  - The investigation on the growth status, community composition, and structural
      characteristics of Pinus tabulaeformis forest artificially tended for six years
      showed that there were significant differences in the average DBH, height, and
      crown size of the forest among the treatments DA (trimming without intermediate
      cutting), FA (trimming and intermediate cutting) and CK (without trending).
      Treatment FA had the highest values of average DBH (7.8 +/- 0.29 cm), height (5.5
      +/- 0.09 m) and crown size (249 +/- 7.24 cm), while the CK had the lowest ones.
      The average biomass of new leaf (1-year-old), old leaf (2 or more-year-old), and
      branch per tree increased significantly (P<0.01) with enhancing tending
      treatments. The aboveground biomass of treatment FA was the biggest (44.0 t x hm(
      2)), and that of CK was the smallest (14.9 t x hm(-2)). The leaf length and SLA
      at the early and terminal stages of development (May, June and September) had
      significant difference among the treatments, and the amount of community
      composition and the cover degree of undergrowth plants increased evidently under
      artificial tending treatments.

PMID- 15943346
TI  - [Niches of several mangrove species in Dongzhai Harbor of Hainan Island].
AB  - Employing the succession series of Kandelia candel-Aegiceras corniculatum
      community in non-indigenous species Sonneratia apetala extension area as resource
      axes, and with three axes, commonly used calculation formulae, this paper
      determined the niche breadth and overlap of mangrove populations. The results
      showed that the niche breadth decreased in order of Aegiceras corniculatum
      (3.8357) > Kandelia candel (3.3421) > Bruguiera gymnorrhiza (3.3180) > Avicennia
      marina (3.0975) > Sonneratia apetala (2.9137) > Sonneratia caseolaris (2.5724) >
      Ceriops tagal (1.8523) > Rhizophora stylosa (1.6897) > Bruguiera sexangula
      (1.0000), which could indicate the ecological adaptability and distribution range
      of the species. The niche overlap among K. candel, A. corniculatum, B.
      gymnorrhiza and A. marina was the largest, suggesting the intense competition
      among them, followed by the niche overlap of S. apetala with S. caseolaris, A.
      corniculatum, K. candel and A. marina, S. apetala with R. stylosa and B.
      sexangula, S. apetala with C. tagal, and S. apetala with B. sexangula.

PMID- 15943347
TI  - [Effects of simulated water stress on photosynthesis rate and WUE of Fraxinus
      mandshurica].
AB  - This paper studied the photosynthesis characteristics and water use efficiency
      (WUE) of Fraxinus mandshurica under three years simulated water stresses 85%-100%
      (CK), 65%-85% (MW) and 45%-65% (LW) of field water-holding capacity. The results
      showed that in comparing with CK, the photosynthesis rate and WUE were higher in
      treatment MW, but decreased by 7.26% and 1.13%, respectively in treatment LW,
      indicating that Fraxinus mandshurica could fully exert its photosynthesis
      potentiality under long-term medium water stress, and was more resistant to
      moderate than to critical water stress. In treatment CK, the diurnal change of Pn
      and WUE was a single and a double peak curve, respectively, while in treatments
      MW and LW, the diurnal change of Pn was a double peak curve, but that of WUE had
      no significant peak, which correlated not only to the physiological
      characteristics of Fraxinus mandshurica under different water stress, but also to
      the diurnal change of environmental factors.

PMID- 15943348
TI  - [Population structure and its dynamics of rare and endangered plant Alsophila
      spinulosa].
AB  - This paper analyzed the population structure of Alsophila spinulosa in seven
      plots by the method of spatial sere substituting for time sere, and measured its
      spatial distribution pattern and dynamics by applying five aggregate indices, C,
      K, m*, m*/m and Idelta. The spatial distribution pattern with different quadrat
      scale was examined, according to the map of individual location. The results
      indicated that the population structure of Alsophila spinulosa in the seven plots
      presented growing, stable, adult or senescent type, and the spatial distribution
      pattern was changed from clump to random with the development of Alsophila
      spinulosa population. The values of dispersion index Idelta of the population
      decreased with increasing quadrat scale.

PMID- 15943349
TI  - [Transpiration water consumption of young Platycladus orientalis and Robinia
      pseudoacacia trees and their correction functions under different water supply].
AB  - Through artificial water control in the shed of rain-free, this paper studied the
      physiological water requirement patterns of 2-3 years old Platycladus orientalis
      and Robinia pseudoacacia trees during their growth period, and the relationships
      between their transpiration water consumption and soil water supply. The results
      showed that the transpiration water consumption of Robinia pseudoacacia was
      increased with increasing soil water supply within the range of 40%-100% of field
      water-holding capacity. Its maximum transpiration water consumption was at the
      early and accelerating growth stages, accounted for 80.5% of total annual water
      consumption. The transpiration water consumption of Robinia pseudoacacia was 5.13
      times as much as that of Platycladus orientalis. Platycladus orientalis had a
      peak value of transpiration water consumption when the soil moisture content was
      40%-100% of field water-holding capacity. Its transpiration water consumption was
      the maximum at accelerating growth stage, accounted for 46.27% of total annual
      water consumption, next at later growth stage, and relatively small at early
      growth stage. The correction functions of transpiration water consumption to soil
      water supply and the time-soil moisture functions of practical transpiration
      water consumption under insufficient water supply for two test species were put
      forward for the first time.

PMID- 15943350
TI  - [Effects of salinity stress on poplars seedling growth and soil enzyme activity].
AB  - A pot culture experiment with two clones of poplars (P1 and P2) showed that soil
      salinity had a definite inhibitory effect on the establishment and growth of
      seedlings. The survival rate, seedling height and weight, and root weight were
      all declined with increasing soil salinity. When the salinity was 0.2%, 0.4%,
      0.6% and 0.8%, the shoot growth of P1 and P2 decreased by 23.24%, 48.56%, 70.76%
      and 83.33%, and 71.77%, 83.25%, 86.28% and 91.39%, respectively, in comparing
      with the control. Regressive analyses showed that soil salinity had a linear
      relationship with chlorophyll content, and a binomial relationship with leaf
      proline content. The activities of soil beta-glucosidase and L-asparaginase were
      decreased with increasing soil salinity. When the salinity was 0.2%, 0.4%, 0.6%
      and 0.8%, the beta-glucosidase activity in P1 and P2 soils decreased by 10.96%,
      20.07%, 30.96% and 37.44%, and 11.21%, 18.94%, 34.89% and 41.31%, respectively.
      The salinity tolerance of P1 was better than that of P2.

PMID- 15943352
TI  - [Alfalfa growth and its relation with soil water status in loess hilly and gully
      region].
AB  - This paper studied the dynamics of alfalfa growth and its relation with the
      excessive depletion and resumption of soil water in loess hilly and gully region.
      The results showed that alfalfa could grow in this region for 10 years, being
      most flourishing at the forth and fifth year, but declined gradually because of
      the excessive depletion of soil water. From 0 to 35 cm above ground, the stem
      biomass was higher than the leaf biomass, and the ratio of stem to leaf was
      1.7:1; at 40 cm above ground, the biomass of stem and leaf was equal; and from 45
      to 90 cm above ground, the leaf biomass was higher than the stem biomass, with
      the ratio of leaf to stem 1.42:1. The soil dry layer was not distinct in first
      two years of alfalfa growth, but getting thicker with time, being from 110 cm in
      third year to 260 cm in seventh year, with a 4.6%-6.2% of soil water content. It
      took 5 years for the natural resumption of soil water in degraded alfalfa
      grassland, and soil water content was increased with time.

PMID- 15943351
TI  - [Effects of NaCl stress on Ca, Mg, Fe and Zn contents of different apple organs].
AB  - The study with two-year-old potted apple tree (Fuji variety with M. hupehensis
      Reld stock) showed that under NaCl stress, the average contents of Ca, Mg, Fe and
      Zn in different apple organs sampled at 4 periods had no significant changes,
      while the content ratios of test elements to Na decreased significantly,
      especially under high NaCl (3 per thousand) stress, which would result in the
      unbalance of mineral nutrients in the tree. The Ca content of different apple
      organs under and without NaCl stress was in order of trunk phloem > leaf and
      vegetative shoot > root > trunk xylem; Mg content was vegetative shoot and root >
      trunk xylem and phloem, and leaf; Fe content was root > leaf > trunk phloem and
      vegetative shoot > trunk xylem; Zn content was vegetative shoot > leaf > root and
      trunk phloem > trunk xylem. The element contents under NaCl stress showed
      different degrees of fluctuation, comparing with the control.

PMID- 15943353
TI  - [Dynamics of soil nitrogen, phosphorus and organic matter in alfalfa-crop rotated
      farmland in semiarid area of Northwest China].
AB  - Pasture-crop rotation is regarded as a key planting system in the semiarid area
      of China's Loess Plateau. This paper studied the dynamics of soil nitrogen,
      phosphorus and organic matter within the two years of alfalfa-crop rotation. The
      results showed that in comparing with continuous alfalfa planting, alfalfa-crop
      rotation induced a decline of soil total nitrogen and organic matter contents by
      5.4% and 19.5%, and 46.8% and 28.2%, respectively, in the first and second year,
      but no significant difference was found in soil total phosphorus. Soil nutrient
      availability was improved due to the rotation. In the first and second year of
      rotation, soil nitrate nitrogen and available phosphorus contents increased by
      15.5% and 159.1%, and 44.5% and 48.0%, respectively. Planting spring wheat could
      maintain soil fertility, the second was fallow and planting potato, while
      planting corn accelerated the depletion of soil total nitrogen, organic matter
      and available phosphorus. As a result, in the alfalfa-crop rotation, planting
      spring wheat could be more available to the maintenance of soil fertility.

PMID- 15943354
TI  - [Soil evaporation under perforated plastic mulch].
AB  - In arid and semiarid regions of northwestern China, where evaporation exceeds
      precipitation, perforated plastic mulches are widely used to decrease soil water
      evaporation. To determine the effects of various perforated plastic mulches on
      soil water evaporation after irrigation, a soil column experiment was conducted,
      which consisted of six mulches with different perforated rates and four levels of
      irrigation, and the soil water evaporation from each soil column was measured.
      The results showed that with 100% perforated mulch, the cumulative evaporation
      was 2.8-48.5 times higher than that of the control, and increased with increasing
      irrigation amount. There was a linear relationship between cumulative evaporation
      and time, which followed the Gardner's theory of bare soil evaporation. A three
      factor (evaporation time, perforated rate and irrigation amount) function of
      cumulative evaporation and the functions of relative cumulative evaporation and
      cumulative evaporation per unit hole area film were established, which fitted the
      observed data very well.

PMID- 15943355
TI  - [Effects of simulated acid rain on physiological and biochemical characters of
      eggplant, the host plant of Tetranychus cinnabarinus].
AB  - In a series of laboratory trials, this paper studied the responses of eggplant
      (Solanum melongena), the host plant of carmine spider mite Tetranychus
      cinnabarinus, to different pH values simulated acid rain. The results showed that
      with the increasing acidity of simulated acid rain, the CAT activity and the
      contents of P and soluble protein in egg plant leaves increased significantly
      first, reaching the highest at pH 4.0 or 3.0, and then decreased; while the POD
      activity and soluble sugar content were in adverse. The reduced sugar content and
      SOD activity of eggplant leaves increased, but the pH value decreased with
      increasing acidity of acid rain. Acid rain had no effect on leaf water content.
      Among the test indices, leaf POD was most insensitive to the acid rain, followed
      by leaf pH, SOD and CAT, while the others were very sensitive. Weak acid rain (pH
      > 4.0) promoted the protective ability of eggplant leaf and its growth, and the
      growth of T. cinnabarinus was also promoted because of the changed contents of
      soluble sugar, P and soluble protein in eggplant leaves being more favorable to
      its eating; while strong acid rain (pH < 3.0) inhibited the growth of both host
      plant and mite.

PMID- 15943356
TI  - [Resource and ecological distribution of ectomycorrhizal fungi under pine forests
      of Huangshan Mountain district].
AB  - Pinus massoniana and Pinus taiwanensis are the most common and important tree
      species in the Huangshan Mountain district, and ectomycorrhizae plays an
      important role in their forestation. Our investigations in 1998-2003 showed that
      under the pine forests of this district, there were 43 species of ectomycorrhizal
      fungi belonging to 10 families and 17 genera, of which, 43 were under Pinus
      massoniana forest, and 12 under Pinus taiwanensis forest. Only a few species were
      found under young Pinus massoniana forest, with the dominant of Pisolithus
      tinctorius (Pers.) Coken and Rhizopogon spp., but under mature Pinus massoniana
      forest, there were plentiful species, with the dominant of Russulaceae,
      Amanitaceae, Boletaceae and Canthurellaceae. The relationships between woody
      species and ectomycorrhizal fungi, and between fungi distribution and
      temperature, moisture and soil condition were discussed in this paper, which
      would benefit to the further studies on the effects of different ectomyrrhizal
      fungi to Pinus massoniana and Pinus taiwanensis forests.

PMID- 15943357
TI  - [Effects of arbuscular mycorrhiza on drought tolerance of Poncirus trifoliata].
AB  - This paper evaluated the effects of arbuscular mycorrhizal colonization on the
      growth and drought tolerance of Poncirus trifoliata in a potted culture under
      natural water stress and resuming water supply. The results showed that the
      arbuscular mycorrhizal colonization by Glomus mosseae 93 could significantly
      increase the plant height, stem diameter, and fresh weight of myocrrhizal plant.
      By the end of the experiment, the survival percentage of transplanted mycorrhizal
      plant was 7.1% higher than that of nonmyocrrhizal plant. During natural water
      stress and resuming water supply, the soluble sugar and soluble protein contents
      and the SOD, POD and CAT activities of root or leaf were higher or significantly
      higher in mycorrhizal than in nonmycorrhizal plant, suggesting that arbuscular
      mycorrhizal colonization could improve the osmoregulatory response of myocrrhizal
      plant, enhance its protective capability, and depress its cell membrane oxidative
      damage to lipids. Consequently, the drought tolerance of inoculated Poncirus
      trifoliata was enhanced. It was considered that the functional mechanism of
      arbuscular mycorrhizal fungus in enhancing the drought tolerance of host plant
      was closely related to the protective systems such as SOD, POD, CAT, and soluble
      protein, etc.

PMID- 15943358
TI  - [Redistribution patterns of black soil in hillslope landform of Northeast China:
      a 137Cs study].
AB  - In the black soil region of Northeast China, soil and water loss is quite
      serious, but not fully investigated due to the lack of reliable methods. 137Cs
      technology is a good one to study the medium-and long term erosion and
      sedimentation rates and the spatial redistribution of soil. With this technology
      and the existing calibration models, this paper studied the redistribution
      patterns of black soil in a typical hillslope landform of Northeast China. The
      results showed that in the study area, the reference 137Cs value was 2232.75 Bq x
      m(-2), intervenient the background values in the Yangtse River Delta and Loess
      Plateau; and the 137Cs areal activity had a great differentiation in horizontal
      and vertical directions, being the lowest in the shoulder-slope positions, which
      suggested that the summits and back-slope positions suffered weak erosion, and
      some of the eroded soils were re-deposited in foot-slope and toe-slope positions.
      The vertical distribution of 137Cs in soil profile ranged from 20 cm on a
      shoulder-slope to 80 cm on a toe-slope position, indicating a significant erosion
      and deposition. Estimations with four existing calibration models showed that PM
      model underestimated while MBM1 model overestimated the soil erosion rates very
      obviously, and both MBM2 and MBM3 gave similar and reasonable estimations.

PMID- 15943359
TI  - [Spatial and temporal differentiation of mountainous soil organic matter delta
      13C in Dinghushan Biosphere Reserve].
AB  - Based on the determinations of soil organic matter (SOM) content, SOM delta 14C,
      and SOM delta13C of the samples collected by thin-layered sampling method, this
      paper studied the spatial and temporal differentiation of SOM delta13 C in the
      soil profiles at different altitudes in Dinghushan Biosphere Reserve. The results
      showed that the vertical differentiation of SOM delta13C at different altitudes
      was controlled by the development of soil profile, and closely correlated with
      the composition of SOM and its turnover processes. The fractionation of carbon
      isotope was happened during both the transformation of vegetation debris into
      topsoil organic matter (OM) and its regeneration after the topsoil buried, which
      resulted in a significant increase of SOM delta13C. Relative to plant debris
      delta13C, the delta13 C increment of topsoil OM was more dependent on its
      turnover rate. Both the delta13C of plant debris and topsoil OM increased with
      altitude, indicating the regular variation of vegetations with altitude, which
      was consensus to the vertical distribution of vegetations in Dinghushan Biosphere
      Reserve. Soil profiles at different altitudes had similar characteristics in
      vertical differentiation of SOM delta13C, vertical distribution of SOM content,
      and increasing apparent age of SOM 14C with soil depth, which were resulted from
      the successive turnover of SOM during the development of soil profile. The
      maximum depth of SOM delta13C in soil profile was different in origin and
      magnitude with the penetration depth of 14C produced by nuclear explosion in the
      atmosphere, indicating the controlling effects of topography and vegetation on
      the distribution of SOM carbon isotope with soil depth.

PMID- 15943360
TI  - [Changes of land use and landscape pattern in Taihu Lake Basin].
AB  - Based on three sets of land use data (1985, 1995 and 2000), and by means of the
      techniques of remote sensing, geographical information system (GIS), and
      landscape ecology, this paper studied the changes of land use and landscape
      pattern from 1985 to 2000 in Taihu Lake Basin located at Yangtse River Delta. The
      results showed that in past 15 years, the farmland in this Basin decreased, while
      the built-up areas, woodland, grassland and water body increased. The decrease of
      the farmland occupied 89.64% of total decrement, while the increase of the built
      up areas accounted for 79.21% of total increment. Under the disturbance of human
      activities, the landscape structure and landscape heterogeneity in Taihu Lake
      Basin changed greatly. The patches density decreased from 0.996 to 0.930,
      diversity indices decreased from 1.127 to 1.113, evenness indices decreased from
      62.891% to 62.109%; while the edge density increased from 4.408 to 4.459,
      dominance indices increased from 0.665 to 0.679, and shape indices increased from
      1.540 to 2.796. The landscape heterogeneity varied with different kinds of
      landscape, indicating the complexity of landscape ecosystem. In all kinds of
      landscapes, farmland and grassland had the highest values of diversity indices.
      The diversity indices of water bodies decreased firstly and then increased, while
      those of built-up areas were in adverse. The evenness index was decreased in the
      order of woodland > farmland > grassland > water body > built-up areas.
      Population, economy and policies were the driving forces of the dynamic changes
      of landscape pattern in Lake Taihu Basin during past 15 years, and land use
      change in the Basin caused distinct landscape effects, such as landscape
      fragmenting, edge effects intensification, and environmental quality declining.
      The mode of land use should be adjusted in landscape scale to rehabilitate and
      reconstruct the landscape ecosystems in Taihu Lake Basin.

PMID- 15943361
TI  - [Ditches protection in lake network based on landscape ecology].
AB  - As a typical corridor landscape in lake network, ditch is an important component
      of lake ecosystem. In recent years, the ecosystem quality of Hanyang lake network
      in Wuhan City becomes worse and worse, mainly caused by the degradation of ditch
      corridor's function. In order to restore its function, this paper made an
      optimized design of the ditches' landscape pattern on the basis of landscape
      ecology theories such as corridor scale effect, heterogeneity, edge effect and
      ecological rehabilitation, and the analyses of ditches status. The contents were
      to control the water quality in the whole area in a larger scale, to dredge and
      rebuild the ditches to strengthen the corridor function, and to project the banks
      of ditches to enhance the anti-disturbance ability. The study indicated that the
      theories of landscape ecology should be used reasonably in the ditches protection
      in lake networks.

PMID- 15943362
TI  - [Relationships between climate change and rice development and its yield
      formation: a simulation study].
AB  - With the application of mechanistic model (RICAM 1.3, RIce growth Calendar
      Model), this paper simulated the rice development and its yield formation under
      different climatic conditions at multi-locations of Asia. A three-stage Beta
      model (3s-Beta) was developed to predict the flowering stage of rice and to
      describe its three successive phases of photo-thermal response, i.e., basic
      vegetative phase, photoperiod-sensitive phase, and post photoperiod-sensitive
      phase. The 1980-1989 multi-location data of Morioka (Japan, 39 degrees 43'N),
      Nanchang (China, 28 degrees 36'N) and Los Banos (Philippines, 14 degrees 11'N)
      were used to verify the suitability of the model in studying ecosystem change.
      Comparisons of simulated results with observed data showed that this model could
      generally predict the eco-physiological processes of rice, and performed very
      well over a wide range of environments.

PMID- 15943363
TI  - [An ecological model for predicting amylose content in rice grain].
AB  - By planting rice varieties Indica and Japonica under different ecological
      environments in China, Japan and Thailand, this study analyzed the relationships
      between the grain amylose content of test varieties and the environmental factors
      including latitude, altitude, temperature and solar radiation during grain
      filling period, established the factor-driven equations for amylose accumulation
      in rice grain, and developed an ecological model for predicting rice grain
      amylose content. The model was validated by using the data of different years,
      sites and varieties, with the RMSE being 0.4% and 0.5% for the grain amylose
      content of Indica and Japonica, and 0.39% and 0.50% for their planting areas,
      respectively. The results indicated that the model was accurate and applicable.

PMID- 15943364
TI  - [Effects of elemental sulphur and dicyandiamide on mitigating NO3- -N leaching
      loss from vegetable soil].
AB  - In a pot experiment with allium as test plant and NH4HCO3 as nitrogen source,
      this paper studied the effects of element sulphur (S0) and dicyandiamide (DCD) on
      mitigating the NO3- -N leaching loss from soil and on soil inorganic nitrogen
      (NO3- -N and NH4+ -N) content. The results showed that within the 12 weeks of the
      experiment, the cumulative leaching loss of soil NO3- -N in treatments S0 + DCD
      and S0 was 83%-86% and 83% lower, while that of soil NH4+ -N was 16.8-21.0 mg x
      pot(-1) and 20.4-25.0 mg x pot(-1) higher than CK, respectively, and the
      cumulative loss of soil (NH4+ + NO3-)-N was 60% lower. By the end of the
      experiment, soil inorganic nitrogen content in treatments S0 + DCD and S0 was
      79.9%-85.4% and 74.9-82.6% higher than CK, respectively. The cumulative leaching
      loss of inorganic N in treatment S0 + DCD was 4.6%-14.4% and 15.4%-30.1% lower,
      and the soil inorganic nitrogen content by the end of the experiment was 6.1% and
      16.8%-36.0% higher than that of treatments S0 and DCD, respectively. Similar
      results were obtained when S0 was replaced by Na2S2O3, but not by Na2SO4. The
      fact that the application of S0 could obviously decrease the NO3- -N leaching
      loss from soil could be contributed to the inhibitory effects of S2O3(2-) and
      S4O6(2-) originated from S0 oxidation in soil on the nitrification of NH4+ -N. S0
      could retard the decomposition of DCD due to the effect of its oxidized products
      S2O3(2-) and S4O6(2-), and thus, extend the inhibitory effect of DCD on NH4+ -N
      nitrification. It is suggested that S0 combined with DCD could be used as an
      effective nitrification inhibitor to control the NO3- -N leaching loss from
      vegetable soils.

PMID- 15943365
TI  - [Foraging habitat selection of Otis tarda dybowskil during its breeding season].
AB  - From April to July of 2000 and 2001, the authors studied the foraging habitat
      selection of Otis tarda dybowskil in the southeast Keerqin of Inner Mongolia by
      sampling method. The results showed that whether at burned or at non-burned
      grassland, the foraging habitat of Otis tarda dybowski had the same feature in
      vegetation structure, the plant height was about 13 cm on average, with the
      highest of 30 cm, and there were abundant species of plants and insects with big
      density that the bird favored to eat. The bird more concerned with the abundance
      of plants at burned grassland, while that of insects at non-burned grassland.

PMID- 15943366
TI  - [Field attraction effects of different trapping methods on Monochamus
      alternatus].
AB  - A comparative study on the field attraction effects of different attractant,
      trap, lure and controlled-releasing amount on Monochamus alternatus showed that
      four test attractants had a certain trapping ability to Monochamus alternatus,
      among which, MA2K05 was the strongest, with a mean capture efficiency of 26.3
      individuals each trap and being attractive to other species of Loleoptera and
      Hemiptera; MA2K13 took the second place, with 21.3 individuals each trap; while
      MA2K11 was the weakest, with 13.8 individuals each trap. Among the three lures
      tested, lures C (60 ml plastic cup with 2 of 5 cm round holes on the cover) and B
      (20 ml specified controlled-releasing plastic bottle) had a comparatively
      stronger effect, with a capture efficiency of 34.25 and 20.3 individuals each
      trap, respectively; while lure A (20 ml specified controlled-releasing plastic
      bottle, the releasing amount being smaller than that of lure B) was the weakest,
      with 14.7 individuals each trap. Because the attractant volume of lure C was 1.5
      times larger than that of lures B and A, and the attractant for lure C was
      appended every 3-5 d, while that for lures B and A could be used for more than a
      month with once appended, lure B was the best on the whole. As for the test
      traps, Xuanzhou trap was superior to imitated Japanese trap, with a trapping
      efficiency of 36.4 and 9.7 individuals each trap, respectively. The
      attractiveness of attractants was not significantly enhanced when the dosage was
      increased from 20 ml to 80 ml, but significantly improved when it was up to 120
      ml.

PMID- 15943367
TI  - [Feeding behavior of Serangium japonicum (Coleoptera: Coccinellidae), a predator
      of Bemisia tabaci (Homoptera: Aleyrodidae)].
AB  - Serangiurm japonicum is an important predator of whiteflies in China. In this
      study, the Bemisia tabaci-attacking behavior of S. japonicum adults and larvae
      was observed by a videocassette recorder. The results showed that the predatory
      behavior of S. japonicum adults was characteristic with six events, i.e.,
      walking, feeding, clearing, resting, vibrating wings, and excreting. The starved
      larvae of S. japonicum was fond spending all times in feeding and walking on host
      eggs, with no time in resting or clearing throughout the process. The time
      included in feeding and walking was not significant different among different
      instars of S. japonicum. The handing time per egg decreased with S. japonicum
      larvae developed from instar I to IV, but differed little between instar III and
      IV. The starved females of S. japonicum spent longer time on egg feeding, but
      less time on clearing, resting and walking than satiated females. The time for
      starved female to predate on B. tabaci nymphs and pupae increased as the host
      nymphs developed.

PMID- 15943368
TI  - [Effects of herbicides on diversity indices of cotton field arthropod community].
AB  - This paper studied the differences of the diversity, abundance and evenness of
      arthropod community and sub-community in cotton field among treatments haloxyfor
      k (A), paraquat (B) and contrast (CK). The results showed that in the diversity
      of phytophagous sub-community, tA-CK = 3.099 and tB-CK = 2.449 (t > t0.05 =
      2.228), the difference being significant, and in the diversity of predatory sub
      community, tA-B = 2.260 and tA-CK = 2.377 (t > t0.05 = 2.228), the difference
      being also significant. In the arthropod community and sub-community, no
      significant difference was found for A-CK, B-CK and A-B. The abundance of
      arthropod community tA- CK = 4.359, and that of phytophagous sub-community tA-CK
      = 2.963, the effect being all significant (t > t0.05 = 2.228). No significant
      difference was found in the evenness of arthropod community and sub-community for
      A-B, A-CK and B-CK. The biodiversity had the same change trend for treatments
      haloxyfor-R (A) paraquat (B) and contrast (CK).

PMID- 15943369
TI  - [Effects of nitrogen supply on nutritional quality and antioxidative enzyme
      activities of spinach].
AB  - A hydroponic experiment was carried out to study the effects of nitrogen (N)
      supply on the nutritional quality and antioxidative enzyme activities of spinach.
      The results showed that when the N supply increased from 4 to 8 mmol x L(-1), the
      biomass of spinach and its leaf vitamin C (Vc) content increased significantly,
      but a further increase of the N supply induced an obvious decrease of Vc content.
      An increasing N supply increased the nitrate content in leaves. The soluble
      oxalate content in leaves decreased slightly with the N supply from 4 to 8 mmol x
      L(-1) N, but increased with a further increase of supplied N. Total oxalate
      content increased firstly, and then decreased with increasing N supply. SOD and
      POD activities increased with the N level up to 8 mmol x L(-1) N, but drastically
      decreased with increasing N levels. CAT activity decreased when N level elevated.
      MDA content decreased firstly and then increased with increasing N levels, while
      free proline content decreased with increasing N supply. All of these indicated
      that 8 mmol x L(-1) N was an appropriate N supply level for spinach to improve
      its biomass, nutritional quality, and resistance.

PMID- 15943370
TI  - [Effects of Bt corn straw decomposition on soil enzyme activities and soil
      fertility].
AB  - An incubation test with the straws of Bt corn 34B24 and its non-transgenic
      isogenic line 34B23, Bt corn Nongda 61, and non-transgenic Nongda 3138 was
      conducted to study the potential effects of Bt corn straw decomposition on soil
      enzyme activities and soil fertility. No significant difference in soil protease
      and acid phosphatase activities was found between treatments 34B24 and 34B23; but
      on day 75 of incubation, soil dehydrogenase activity was significantly higher in
      treatment 34B24 than in treatment 34B23. The same was true for soil invertase
      activity on days 15,45, 60 and 75. Soil urease activity in treatment 34B24 was
      significantly increased on day 30, but decreased on days 45 and 75. A significant
      difference in several soil enzyme activities was also observed between the
      treatments of two Bt corn hybrids and their conventional cultivars at some
      sampling days. After incubation for 90 days, the contents of soil available P and
      K were significantly lower in treatment 34B24 than in treatment 34B23. The
      differences mentioned above resulted from the composition of test corn straws,
      which may be affected by the Bt gene transformation process. In order to
      accurately assess the effects of Bt corn straw decomposition on soil ecosystem, a
      standard classification system of soil enzyme activities should be established
      for different soil types from different regions.

PMID- 15943371
TI  - [Effects of Alternaria azukiae on physiological metabolism and active oxygen
      eliminating enzyme activities of Trifolium repens].
AB  - A pot experiment was installed to study the effects of Alternaria azukiae
      inoculation on the cell membrane permeability, pigment and MDA contents, and
      activities of SOD, POD and CAT of Trifolium repens. The results showed that A.
      azukiae infection made T. repens leaf tissue increase its cell membrane
      permeability, electric conductivity, over-oxidation and MDA content, but decrease
      its pigment content. The electric conductivity and MDA content were positively
      related with infection time, whereas the pigment content was negatively related
      with it. Due to the stimulation by A. azukiae, the over-oxidation of cell
      membrane was intensified, which resulted in a large amount of active oxygen
      accumulated and beyond the defense ability, the active oxygen metabolism system
      was destroyed, and the balance of protective enzyme system was broken. After 12
      days of A. azukiae inoculation, the activities of SOD and CAT decreased by 55.2%
      and 37.8%, respectively, while the POD activity increased by 1.6 times.

PMID- 15943372
TI  - [Effects of oxalate on acid phosphatase adsorption and its activity on soil
      colloids and minerals].
AB  - By a batch method, this paper studied the effects of different concentration and
      pH of oxalate, an important root exudate, on the adsorption of acid phosphatase
      and its activity on < 2 microm colloids of yellow brown soil and latosol, and on
      minerals goethite and kaolinite. The results showed that the acid phosphatase
      adsorption by goethite was less affected by the concentration of oxalate; while
      the adsorbed amount of this enzyme by the other test colloids and kaolinite was
      sharply decreased with the increasing oxalate concentration (0-5 mmol x L(-1))
      first, and then gradually increased to the level equal to or less than the blank,
      which may be related to the coordination type of oxalate on soil colloids and
      minerals, and their surface charge change and dissolution. In the systems oxalate
      existed, the adsorbed amount of acid phosphatase by soil colloids and minerals
      decreased in order of goethite >> yellow brown soil > kaolinite > latosol. The pH
      value for the maximum adsorption of acid phosphatase was between the IEP of the
      enzyme and the PZC of test colloids and minerals. After the enzyme was
      immobilized on colloids and minerals, the pH of its maximum specific activity had
      no change, or shifted to a higher value.

PMID- 15943373
TI  - [CH4 and N2O emission from a winter-time flooded paddy field in a hilly area of
      Southwest China].
AB  - By the method of static opaque chamber/modified gas chromatography, a one-year
      field experiment was conducted to measure in situ the CH4 and N2O emission from a
      winter-time flooded paddy field in a hilly area of Southwest China. Gas samples
      were taken simultaneously from rice-involved and rice-uninvolved plots. The
      results showed that during rice growth period, the CH4 emission from the winter
      time flooded paddy field was higher than that from other paddy fields, but
      largely lower than many previous reports for the similar regions in Southwest
      China. The average flux of CH4 emission from rice-involved plots was 22.76 +/-
      2.76 mg CH4 x m(-2) x h(-1) during rice growth period, 9.64 +/- 1.17 mg CH4 x m(
      2) x h(-1) per year, and 1.43 +/- 0.20 mg CH4 x m(-2) x h(-1) during non-rice
      growth season; while that from rice-uninvolved plots was only 2.03 +/- 0.18 mg
      CH4 x m(-2) x h(-1) per year, markedly lower than those from rice-involved plots.
      During rice growth season, the mean emission rate of CH4 and N2O was 4.53 +/-
      0.38 mg CH4 x m(-2) x h(-1) and 32.01 +/- 5.02 microg N2O x m(-2) x h(-1) from
      rice-uninvolved plots, but reached to 22.76 +/- 2.76 mg CH4 x m(-2) x h(-1) and
      73.04 +/- 5.03 microg N2O x m(-2) x h(-1) from rice-involved plots, respectively.
      Rice involvement resulted in 302% increment of CH4 and 128% increment of N2O
      emission. There was a clear trade-off between CH4 and N2O emission in paddy
      fields. Even with a span of 500 years, our calculation showed that in this winter
      time flooded paddy field, the GWP contributed by N2O production was 7.9% of the
      CH4 contribution, and thus, the greenhouse effect of N2O production from this
      field was very small.

PMID- 15943374
TI  - [Responses of soybean to O3, CO2 and their combination].
AB  - With cultivar "Zhonghuang 14" as test crop, this paper studied the effects of CO2
      and/or O3 on the growth and development of soybean (Glycine max L.) in an open
      top chamber. The results showed that an increasing CO2 concentration could defer
      the leaf's O3 injury, and relax the injury degree. After treated with CO2 for 20
      days, the stoma resistance and transpiration rate of soybean leaves had little
      difference with CK. Only when fumed with high concentration CO2 and O3, the stoma
      became closed, stoma resistance increased, and transpiration rate decreased
      obviously. Compared with ambient atmospheric CO2 and O3 (CK), doubled CO2
      significantly increased the dry matter accumulation and grain yield, reduced the
      coarse fat and raw protein contents of grain, but the harvest index had no
      obvious difference; while doubled 03 decreased the dry matter accumulation, grain
      yield and harvest index of soybean, reduced the coarse fat content, but increased
      the raw protein content of grain. The interaction of doubled CO2 and O3 had no
      obvious effects on the dry matter accumulation, grain yield and harvest index of
      soybean, but reduced the grain raw protein content to a certain extent and
      increased the coarse fat content obviously.

PMID- 15943375
TI  - [Distribution, migration and purifying effect of cadmium in artificial Avicennia
      marina wetland system].
AB  - An artificial mangrove Avicennia marina wetland was set up in a greenhouse, and
      an irrigation experiment with synthetic wastewater was performed to research the
      behavior of cadmium in the artificial wetland system. The synthetic wastewater C1
      had the characteristics and strength similar to normal municipal sewage, while C5
      and C10 had the nutrients and heavy metals as five and ten times as those in C1,
      respectively. The control was of 15 per thousand salinity. All the test
      wastewater was quantitatively irrigated weakly for a year. The results showed
      that the cadmium in the synthetic wastewater discharged into the system was
      mainly stagnated in soil subsystem (87.67%-96.74%), and only a small portion
      (0.43%-3.23%) migrated into plants and litters. After a year trial, the Cd
      content in roots was more than that in stems and leaves. The artificial Avicennia
      marina wetland system did have a significant effect on purifying cadmium in
      synthetic wastewater, and the purification rate for C1, C5 and C10 was 90.43%,
      97.17% and 97.06%, respectively.

PMID- 15943376
TI  - [A new precipitation distribution hydrological model and its application].
AB  - In distribution hydrological models, precipitation is the key input data for
      analyzing and computing hydrological processes. Finding a way to produce
      distribution precipitation data is a hotspot in hydrological research. This paper
      presented the hypothesis that the distribution of precipitation on the earth
      surface is the result of the effects of atmosphere system and terrain. Moreover,
      the spatial distribution of natural precipitation is a group of concentric ovals
      on the flat earth surface, and has a definite centre with maximum precipitation
      not affected by terrain. Supporting by the hypothesis, this paper established a
      new precipitation distribution hydrological model which could simulate the
      spatial distribution of precipitation, and modified the terrain effect on
      precipitation through Newton interpolation. The position of the precipitation
      centre and its precipitation amount were simulated in first time, and thus, the
      model could have a practical value in basin storm analysis and real-time runoff
      forecasting. The model was tested by the precipitation data of the Xichuan river
      basin in the Loess Plateau, which indicated that the model had a high precision.

PMID- 15943377
TI  - [Effects of UV-B radiation enhancement on DNA damage of three red-tide microalgae
      species].
AB  - The ecotoxicological and biochemical study with Heterosigma akashiwo, Alexandrium
      tamarense and Skeletonema costatum showed that the test three species of red-tide
      microalgae had different sensitivities to UV-B radiation enhancement, and the
      order from high to low was Heterosigma akashiwo, Alexandrium tamarense and
      Skeletonema costatum. The DNA damage of algal cells increased with UV-B radiation
      enhancement, being more notable in Heterosigma akashiwo than in Alexandrium
      tamarense and Skeletonema costatum, and in Alexandrium tamarense than in
      Skeletonema costatum. The DNA damage of Heterosigma akashiwo and Alexandrium
      tamarense could be significantly repaired (P < 0.05) after 6 days of UV-B
      radiation removal, and that of Skeletonema costatum could be significantly
      repaired (P < 0.05) after 3 days, which illustrated that the DNA damage of three
      red-tide microalgae species could not indicate the damaged degree of marine
      microalgae resulted from UV-B radiation enhancement.

PMID- 15943378
TI  - [Bioavailability of cadmium in seawater to Paralichthys olivaceus].
AB  - With exposure experiment, this paper studied the accumulation and elimination of
      cadmium (Cd) in the viscera, muscle and gill of Paralichthys olivaceus, and the
      effects of TOC concentration in seawater on the Cd accumulation. The results
      showed that when the exposure concentration of Cd was 0.5 mg x L(-1), its
      accumulation in test tissues increased with time, and reached equilibrium on the
      10th day. The accumulation was in order of viscera (147.73 mg x kg(-1) DW) > gill
      (15.55 mg x kg(-1) DW) > muscle (4.578 mg x kg(-1) DW), which meant that viscera
      was the main place for Cd accumulation. Determinations after moving the fish into
      clear seawater on the 13th day of exposure showed that due to depuration, the Cd
      accumulation in test tissues decreased with time. On the 15th day after moving,
      the Cd elimination was in order of viscera (80.66%) > gill (73.66%) > muscle
      (56.84%), suggesting that the Cd accumulation in Paralichthys olivaceus could be
      reduced to meet safe food standard. The TOC concentration in seawater had a
      significant effect on Cd accumulation, i.e., the accumulation of Cd decreased
      significantly with increasing TOC concentration, demonstrating that the TOC in
      seawater could decrease the bioavailability of cadmium.

PMID- 15943379
TI  - [Alien species invasion in Southern China and its countermeasures].
AB  - Alien species invasion may cause serious ecological damage, resulting in
      ecological crisis and biodiversity comedown, and further menacing existing human
      environment. At present, the invasion of alien species has brought very serious
      damage to China's environment and society. The direct annual loss of its agro
      forestry industry accounts for 574 billion RMB. Taking the alien species in
      Southern China as an example, this paper analyzed the bio-invasion approaches,
      mechanics and damages, and aiming at the characters of invaded area and concerned
      ecosystems and species, proposed several prevention measurements, i.e., pay
      attention to the phenomena of bio-invasion and to the basic researches on it;
      intensify the legislation and establish scientific strategies for introducing
      alien species; enforce the quarantine on invasive species and establish
      countrywide monitoring system on alien species; enhance people's defending
      consciousness; and strengthen international cooperation and collaboration.

PMID- 15943380
TI  - [Maintaining mechanism of species diversity of land plant communities].
AB  - The maintaining mechanism of species diversity of land plant communities is a key
      and advancing edge in biodiversity study. Botanists and ecologists have presented
      many hypotheses and theories with controversies, and no general theory system was
      available. In this paper, the problem was reviewed mainly on two scales. The
      first was big spatial scale, aiming at the physical and natural factors that
      affect the species diversity, including histories and ages of plant communities,
      gradient changes such as latitude gradient, water gradient, altitude gradient and
      soil nutrients gradient, area effect, and isolation; and the second was
      concentrated on a special plant community, and mainly discussed the relationships
      of biodiversity with biotic factors (primary productivity, relationship between
      species, and gap dynamics) and abiotic factors (succession, disturbance and
      spatial heterogeneity, and human activity).

PMID- 15943381
TI  - [Farmland nitrogen loss and its control strategies from the view of water
      environment].
AB  - Nitrogen is a major factor in maintaining crop yield and getting better economic
      return, but its over-and unreasonable use may cause severe environmental
      pollution. From the view of water environment, this paper discussed the current
      effects of farmland nitrogen (N) loss on water pollution, the passes and
      mechanisms of farmland nitrogen loss, and its control strategies. To reduce the N
      surface runoff and leaching, effective measures should be taken, which include
      cutting down the paths from the source to transportation, and taking integrated
      measures to control N pollution. The BMPs (Best Management Practices) methods for
      N control suitable to China's situation were discussed on the basis of nitrogen
      source pollution rate.

PMID- 15943382
TI  - [Phosphatase activities in rice-planting meadow brown soil and their responses to
      fertilization].
AB  - This study is aimed to investigate the activities of phosphomonoesterase (acid-,
      neutral-, and alkaline-), phosphodiesterase and phosphotriesterase in a rice
      planting meadow brown soil at the lower reach of Liao River, and their responses
      to different fertilization treatments. The results showed that there was no
      significant difference in soil total P and organic P contents among all
      treatments, but soil available P content was significantly higher in treatment OM
      than in other treatments. Soil acid-and neutral phosphomonoesterase had a higher
      activity than alkaline phosphomonoesterase and phosphodiesterase, while
      phosphotriesterase had the lowest activity. No significant difference was found
      in phosphatase activities between different fertilization treatments. Soil acid
      phosphomonoesterase activity had a significant correlation with soil total P and
      available P contents, while soil phosphodiesterase activity significantly
      correlated with soil organic P content.

PMID- 15943384
TI  - The challenge of tracking whales: lessons from the study of changing health
      policy.

PMID- 15943383
TI  - [Effects of different light source and dark-adapted time on phototactic behavior
      of cotton bollworms (Helicoverpa armigera)].
AB  - In this paper, the phototactic behaviors of different emergence period
      Helicoverpa armigera were studied in a phototactic box. The results showed that
      under the five test wavelength lights, different emergence period female and male
      moths had no significant difference in their phototactic behaviors. The
      phototactic rate differed significantly when the dark-adapted time was between 15
      and 30 min, but had no significant difference among 30, 45 and 60 min. No
      significant difference was also found in phototactic rate between dark-adapted
      time 0 and 15 min under test wavelength lights except green one (500-565 nm).

PMID- 15943385
TI  - European health systems reforms: looking backward to see forward?
AB  - In this article we outline the different schools of new institutionalism and a
      few other selected political science theories. Moreover, we relate the insights
      offered by a series of analyses of health sector change in a large number of
      European countries over the past twenty to thirty years to these theoretical
      frameworks. Our main conclusion is that it is unlikely that a single explanatory
      theory will ever be able to account for all of the health sector developments in
      any one country, let alone across many countries with diverse cultures,
      histories, institutions, and interest groups. Consequently, a real understanding
      of health sector change will require a recognition that different theoretical
      approaches will be more (or less) appropriate in some circumstances than in
      others.

PMID- 15943386
TI  - Health policy in Denmark: leaving the decentralized welfare path?
AB  - In this article, we investigate developments in Danish health care policy. After
      a short presentation of its historical roots, we focus on the decades after the
      administrative reform of 1970, which shaped the current decentralized public
      health care system. Theories of path dependency and institutional inertia are
      used to explain the relative stability in the overall structure, and theories of
      policy process and reform are used to discuss gradual changes within the overall
      framework. Although comprehensive reforms have not taken place in Denmark, many
      gradual changes may pave the way for more radical changes in the future. The
      political climate currently seems to be more favorable toward structural reform
      than in the past.

PMID- 15943387
TI  - The interplay between economic and political logics: path dependency in health
      care in England.
AB  - The purpose of this article is to use the ideas of path dependency to understand
      why policies implemented by governments for health care in England were and are
      suboptimal in terms of the control of total costs, the equitable distribution of
      hospital services, and efficiency in delivery. We do this by relating the
      economic logic of achieving these objectives to the political logic of a state
      hierarchical system in which ministers are accountable for the effects of
      policies and doctors largely decide the supply and demand of health care. The
      initial policy path of the National Health Service (NHS) controlled costs but
      lacked systems to achieve equity and efficiency in the funding of hospitals.
      Policies were introduced to achieve equity, but not efficiency, in the 1970s. The
      Thatcher government sought efficiency through a budgetary squeeze in the 1980s,
      which culminated in the NHS funding crisis of 1987 - 1988. The result was the
      policies of the NHS internal market, which promised efficiency by introducing a
      purchaser-provider split and a system of provider competition in which money
      would follow the patient. These promises justified an injection of extra funds
      for three years, but only a pallid model of the internal market was implemented.
      The Blair government abandoned the rhetoric of competition but maintained the
      purchaser-provider split and continued to constrain total NHS costs, which
      resulted in the funding crisis of 1998 - 1999. Current policies are to
      substantially increase spending on health care and reintroduce a system of
      provider competition in which money will follow the patient.

PMID- 15943388
TI  - Reform, change, and continuity in Finnish health care.
AB  - This article describes some essential aspects of the Finnish political and
      governmental system and the evolution of the basic institutional elements of the
      health care system. We examine the developments that gave rise to a series of
      health care reforms and reform proposals in the late 1980s and early 1990s and
      relate them to changes in health care expenditure, structure, and performance.
      Finally, we discuss the relationship between policy changes, reforms, and health
      system changes and the strength of neo-institutional theory in explaining both
      continuity and change. Much of the change in Finnish health care can be explained
      by institutional path dependency. The tradition of strong but small local
      authorities and the lack of legitimate democratic regional authorities as well as
      the coexistence of a dominant Beveridge-style health system with a marginal
      Bismarckian element explain the specific path of Finnish health care reform.
      Public responsibility for health care has been decentralized to smaller local
      authorities (known as municipalities) more than in any other country. Even an
      exceptionally deep economic recession in the early 1990s did not lead to systems
      change; rather, the economic imperative was met by the traditional centralized
      policy pattern. Some of the developments of the 1990s are, however, difficult to
      explain by institutional theory. Thus, there is a need for testing alternative
      theories as well.

PMID- 15943389
TI  - State autonomy, policy paralysis: paradoxes of institutions and culture in the
      French health care system.
AB  - In this article, we assess the recent performance of the French state at
      containing costs in health care using political science concepts such as path
      dependency and incentives, which are central to an economic approach. The article
      focuses on institutional capacities and cultural immobilism and attempts to lay
      bare the tensions at play in seizing (or not) opportunities for structural
      change. In particular, we attempt to delineate what constitutes real change in
      this policy arena (big reforms versus the accumulation of many small policy
      movements) and to understand the variables at play in the coming together of
      conjunctures that provide for the big, as well as the underlying structures that
      allow the accumulation of the small. Except in cases of favorable conjuncture,
      the analysis bodes very ill for nonincremental reform and, indeed, for
      significant change over the long term.

PMID- 15943390
TI  - Health care reform in Germany: patchwork change within established governance
      structures.
AB  - Under the pressure of health care reform in the 1990s, interactions among the
      state, sickness funds, and providers in Germany are said to have entered a new
      era. We examine this new era by assessing both long-term developments connected
      to German statutory health insurance (SHI) and related short-term developments of
      the 1990s. Highly institutionalized rules and practices provide little
      opportunity for abandoning the historical path of two primary factors: the self
      governance of SHI and a strong tradition of a semisovereign state. Some
      opportunities exist for introducing new ideas, rearranging priorities, softening
      rules, and adding new complex rules and procedures in a fairly fragmented policy
      making system, perhaps even because of fragmentation. Yet reforms that depart
      from the status quo are severely limited by strong legal and administrative
      traditions and established rules of the game. These restrictions tend to
      reinforce state intervention, prevent the emergence of consistent and coherent
      visions of future health policy, and stifle policy innovation and implementation.
      In sum, reform measures tend to remain well within the priorities established
      within state and corporatist governance structures.

PMID- 15943391
TI  - Plus ca change: health sector reforms in Greece.
AB  - Changes in the health care sector in Greece since the pathbreaking introduction
      of the National Health System (NHS) in 1983 have been sluggish. Twenty years
      after its inception and a series of attempts to reform it, the NHS remains
      centralized, fragmented in terms of coverage, and quite far removed from its
      principles of equity and efficiency. Being part of an idiosyncratic welfare
      state, the health care system is bound to reflect the particularities of Greek
      society and economy, namely, clientelism, a weak formal-and a thriving informal
      economy, the lack of a strong administrative class, a weak labor movement, and
      strong organized interests. As a result, several ambitious reform plans have
      failed repeatedly owing to an array of interrelated economic, political, and
      social factors that channel potential changes toward the trodden path. This
      constellation creates unfavorable conditions for the introduction and
      implementation of major reforms.

PMID- 15943392
TI  - The evolution of health-policy making in Italy.
AB  - An analysis of the dynamics of health care policy in Italy suggests that in
      recent years the pace of change in the health care system has accelerated.
      Although the basic features of universalism, comprehensiveness, and funding from
      general taxation have remained remarkably constant, the capacity to innovate
      policy tools and their settings and to take account of domestic and international
      experience seems to have increased. The political will and capacity to combat
      entrenched interests may also have increased, although implementation is still
      weak. The imperative to contain public expenditure has heavily conditioned health
      policy and will continue to do so. This has occurred mainly at the national
      level, but as the principal locus of health-policy making progressively shifts to
      the regions, so too will the constraining effect of this imperative move
      downward. If the decentralization process continues, problems could arise due to
      interregional differences in capacities to formulate and implement appropriate
      policies and to tackle special interest groups.

PMID- 15943393
TI  - Market-oriented health care reforms and policy learning in the Netherlands.
AB  - In this article we analyze the evolution of market-oriented health care reforms
      in the Netherlands. We argue that these reforms can be characterized as policy
      learning within and between competing policy programs. Policy learning denotes
      the process by which policy makers and stakeholders deliberately adjust the
      goals, rules, and techniques of a given policy in response to past experiences
      and new information. We discern three distinctive periods. During the first
      period (1988-1994), the prevailing corporatist and etatist policy programs were
      seriously challenged by the proponents of a new market-oriented program. But when
      it came to political decision making and implementation, the market-oriented
      program soon lost its impetus because it was technically too complex and could
      not provide short-term solutions to meet the urgent need for cost containment.
      During the second period (1994-2000), the etatist program regained its previously
      dominant position. In parallel to a strengthening of supply and price controls,
      however, the government also persevered in creating the technical and
      institutional preconditions for regulated competition. Moreover, public
      discontent over waiting lists and the call for more autonomy by individual
      providers and insurers strengthened the alliance in favor of regulated
      competition. This led to the revival of the market-oriented program in a 2001
      reform plan. We conclude that the odds of these new post-2001 reforms succeeding
      are substantially higher than in the first period due to the technical and
      institutional adjustments that have taken place in the past decade.

PMID- 15943394
TI  - Nondecision making and inertia in Portuguese health policy.
AB  - Despite there having been a positive context for initiating health care reforms
      in Portugal in the past fifteen years (accompanied by political consensus on the
      nature of the structural problems within the health care system), there has been
      a lack of reform initiatives. We use a process-based framework to show how
      institutional arrangements have influenced Portuguese health care reform.
      Evidence is presented to demonstrate inertia and nondecision making in three
      critical areas of Portuguese health policy: clarifying the public-private mix in
      coverage and provision, creating financial incentives and motivation for human
      resources, and introducing changes in the pharmaceutical market. Several factors
      seem to explain these processes, namely, problems in the balance of power within
      the political system, which have contributed to a lack of proper policy
      discussion; a lack of pluralism in the formation of health care policies (with
      low participation from citizens and high mobilization among structural interest
      groups); and the low priority of health care in public sector reforms. Portuguese
      politicians should be aware of the pitfalls of the current political system that
      constrain participatory arrangements and pluralism in policy making. In order to
      pursue health care reform, future governments will need to counterbalance the
      strong influence of structural interest groups.

PMID- 15943395
TI  - Power rather than path dependency? The dynamics of institutional change under
      health care federalism.
AB  - Proposals for government decentralization rank high on the political reform
      agenda of health systems worldwide. Their impact on welfare state performance and
      change, however, is still under theoretical scrutiny. This article examines the
      impact of devolution on the construction of the Spanish National Health Service
      (NHS) in an attempt to shed some light on this debate. Against widespread claims
      of path dependency, we argue that the specific nature of the devolution model
      developed in Spain, given the more egalitarian sociopolitical structure that
      resulted from democratization, fostered policy innovation and institutional
      change. Consolidation of an NHS system was compatible with some regional
      diversity and apparently prevented the rise of significant territorial
      inequalities. The Spanish case also suggests that policy change depends more on
      the distribution of social power than on institutions. It underlines the key role
      of financial and knowledge transfers vis-a-vis institutional reforms in effecting
      social change as well as the potential for state intervention in supporting the
      development of collective action resources by social groups.

PMID- 15943396
TI  - Renovating the Commons: Swedish health care reforms in perspective.
AB  - Recent reform experience in Sweden supports the premise that key dimensions of a
      country's health care system reflect the core social norms and values held by its
      citizenry. The fundamental structure of the Swedish health system has remained
      notably consistent over the past half century, that is, tax-based financing and
      publicly operated hospitals. Yet on other, nearly as important, parameters, there
      has been substantial change, for example, the persistent pursuit for thirty years
      of a stronger primary care framework and the effort to allow patient choice of
      doctor, health center, and hospital within the publicly operated system. This
      particular combination of continuity and change has occurred as traditional
      Swedish values of jamlikhet (equality) and trygghet (security) have been
      challenged in an environment shaped by an aging population, changing medical
      technology, and Sweden's integration into the European Single Market. This
      article explores the ongoing process of health system development in Sweden in
      the context of the country's broader social and cultural characteristics.

PMID- 15943397
TI  - Fellow travelers on a contested path: power, purpose, and the evolution of
      European health care systems.

PMID- 15943398
TI  - Long-term follow-up after robotic cholecystectomy.
AB  - Most surgeons gain their first clinical experience with surgical robots when
      performing cholecystectomies. Although this procedure is rather easily applicable
      for the da Vinci surgical system, the long-term outcome after this operation has
      not yet been clarified. This study follows up our institutional first series of
      robotic cholecystectomies (June to November 2001). Patients were assessed on the
      basis of standardized management including a quality-of-life questionnaire,
      clinical examination, blood tests, and abdominal sonogram. The follow-up rate for
      23 patients after robotic cholecystectomy was 100 per cent and the median follow
      up time 33 (30-35) months. There was one (4%) recurrence of gallstone disease in
      a patient who suffered from solitary choledocholithiasis 29 months after robotic
      cholecystectomy. Abdominal sonogram, clinical examinations, and blood tests
      revealed no post-cholecystectomy-specific pathological findings. The main long
      term symptoms were bloating (57%), heartburn (43%) and nausea (30%). Of the
      patients, 96 per cent (22 patients) felt that the operation had cured or
      significantly improved their specific preoperative symptoms. Long-term results
      after robotic laparoscopic cholecystectomy are excellent and comparable to those
      for the conventional laparoscopic procedure. The advanced vision control and
      instrument maneuverability of robotic surgery might open minimally invasive
      surgery also for complicated gallstone disease and bile duct surgery.

PMID- 15943399
TI  - Cadaveric kidney transplant complicated by rupture of native kidney
      angiomyolipoma: a case report and review of the literature.
AB  - Kidneys with angiomyolipomas have been used for transplantation, but we are
      unaware of postoperative hemorrhage from a native kidney angiomyolipoma. A 49
      year-old male who underwent a cadaveric renal transplant complicated by
      postoperative hemorrhage from a native kidney angiomyolipoma is presented.
      Evaluation and current management strategies are discussed.

PMID- 15943400
TI  - Video-assisted thoracoscopic division of vascular rings in pediatric patients.
AB  - Vascular rings are usually repaired via left thoracotomy. We report our series of
      pediatric patients with vascular rings that were repaired thoracoscopically. From
      February 2002 to September 2004, 13 patients underwent video-assisted
      thoracoscopic surgical techniques (VATS) division of their vascular ring. Chest
      magnetic resonance arterography (MRA) and/or computed tomographic arteriography
      (CTA) were used to evaluate the vascular ring in most patients. Patients were
      chosen for VATS repair based on surgeon's choice and type of vascular ring. Data
      are expressed as mean +/- SD. The Children's Healthcare of Atlanta Institutional
      Review Board approved this retrospective chart review. Age and weight was 1.5 +/-
      1.8 years (range: 4 months - 17 years) and 16.0 +/- 12.5 kg (range: 6.0 - 22.1
      kg), respectively (n = 13). Associated diseases included congenital heart disease
      (n = 2). Symptoms included respiratory complaints (n = 6), dysphagia (n = 2),
      dysphagia and shortness of breath (n = 1), pneumonia (n = 2), tracheal deviation
      (n = 1), and one patient was asymptomatic. Vascular ring types included double
      aortic arch (n = 4) and right aortic arch with an aberrant left subclavian artery
      and a left ligamentum arteriosum (n = 9). Operating time was 70 +/- 20 minutes
      (range: 46 - 122 minutes). One patient had to be opened because of a large arch.
      Length of stay was 1.9 +/- 0.9 days (range: 1 - 3 days). There were no
      complications, and all patients improved clinically at follow-up. Thoracoscopic
      repair of certain types of vascular rings seems to be safe and effective in
      children. More patients, however, need to be studied.

PMID- 15943401
TI  - Mucinous cystadenoma of the pancreas associated with acute pancreatitis and
      concurrent pancreatic pseudocyst.
AB  - We report an unusual occurrence of a recurrent pancreatic pseudocyst caused by an
      underlying mucinous cystadenoma of the distal pancreas. A 54-year old female was
      admitted for acute pancreatitis. Her only risk factors included the use of
      hydrochlorothiazide and two or three glasses of wine daily. Abdominal computed
      tomography (CT) done a week after onset of her symptoms showed a 5-cm cystic
      lesion in the tail of the pancreas suspected to be a pseudocyst. Her symptoms
      subsequently resolved. One month later, she had another episode of pancreatitis
      and an abdominal CT showed an 11 x 16 cm pseudocyst along with the previously
      mentioned cystic lesion. Approximately 6 weeks after her initial presentation,
      she was taken to the operating room for an exploratory laparotomy and cyst
      gastrostomy for a symptomatic pseudocyst. An intraoperative frozen section of the
      cyst wall showed a fibrous wall with acute and chronic inflammation without an
      epithelial lining. Six weeks after her cyst gastrostomy, she returned with
      abdominal pain, early satiety, and anorexia. Abdominal CT showed reaccumulation
      of fluid within the pseudocyst and endoscopic retrograde cholangiopancreatography
      (ERCP) revealed a normal caliber pancreatic duct with an abrupt cutoff at the
      distal duct. She underwent exploratory laparotomy with drainage of 3 L of fluid
      from the pancreatic pseudocyst. After gaining access to the lesser sac, a 6-cm
      cystic lesion was identified in the tail of the pancreas. She underwent a distal
      pancreatectomy and splenectomy. The intraoperative and final pathology confirmed
      the presence of a benign mucinous cystadenoma. The patient had an uneventful
      recovery, began to tolerate oral intake, and was discharged 7 days after surgery.
      The differentiation between a pancreatic pseudocyst and benign cystic neoplasms
      of the pancreas is crucial to determine treatment options. Cystic neoplasms of
      the pancreas, whether mucinous or serous, have the potential to harbor
      malignancy, and resection is recommended.

PMID- 15943402
TI  - Twenty-millimeter laparoscopic cholecystectomy: fewer ports results in less pain,
      shorter hospitalization, and faster recovery.
AB  - Improvements in technology offer the ability to refine operations without
      compromising safety. In this study, we determine whether a modified method of
      laparoscopic cholecystectomy using three ports and an aggregate incision length
      of 20 mm offers any advantage or poses increased risk. Using a 5-mm, 30 degree
      laparoscope, clip applier, and dissector, the gall bladder is removed through an
      extended umbilical incision. Standard safety principles were followed: achieving
      the "critical view," lateral retraction of the fundus, double ligation of the
      proximal structures, and maintaining sterility for specimen removal. Forty-one
      consecutive standard laparoscopic cholecystectomies were used as a control group
      to compare complications, length of stay and surgery, pain scores, and return to
      work. Sixty patients have undergone the modified technique. There were no
      differences between the modified and standard technique with regard to cost or
      complications. Length of surgery was significantly shorter, as was length of
      stay, narcotics use, and return to work for the modified group versus the
      control. A modified technique for laparoscopic cholecystectomy poses no increased
      risk to patients but offers potential for shorter surgery and hospital stays,
      less need for narcotic analgesia, and faster recovery.

PMID- 15943403
TI  - Management of subclavian and axillary artery injuries: spanning the range of
      current therapy.
AB  - Injuries of the subclavian and proximal axillary arteries are potentially
      devastating but account for a minority of vascular injuries presenting to trauma
      centers in the United States. We have reviewed our recent experience with
      management of subclavian and axillary artery injuries in a state-designated level
      1 academic trauma center and report four cases that illustrate the typical
      arterial injury patterns and the entire therapeutic armamentarium in its current
      iteration. Subclavian and proximal axillary artery injuries present as
      interesting surgical problems. A high index of suspicion for vascular injuries
      should be maintained given the mechanism and proximity to major vasculature.
      Consideration should always be given to the least invasive treatment options in
      stable patients. Awareness of multiple therapeutic modalities and indications for
      each should be an integral part of every surgeon's armamentarium. As with all
      vascular intervention, eventual failure is the rule rather than the exception;
      therefore, plans for longitudinal surveillance should be made independent of the
      technique used to treat the injury.

PMID- 15943404
TI  - National study of the effect of patient and hospital characteristics on bariatric
      surgery outcomes.
AB  - The influence of patient and hospital demographics on gastric bypass (GB)
      outcomes is unknown. We analyzed year 2000 data from the Nationwide Inpatient
      Sample database for all GB patients. In 2000, 5876 GB were performed in the 137
      sample hospitals (M:F, 14%:86%). Length of stay (LOS, days), charges,
      comorbidities, and morbidity were higher for those aged >60 years compared to <
      40 years. LOS, charges, comorbidities, morbidity, and mortality were highest in
      males. LOS was longest in African Americans compared to Caucasians and Hispanics.
      Charges and comorbidities were greatest in African Americans and Hispanics
      compared to Caucasians. Medicare and Medicaid-insured patients have higher LOS,
      charges, comorbidities, morbidity, and mortality compared to privately insured
      and self-pay patients. Lower income patients have higher LOS and total charges.
      Nonteaching hospitals have an increased LOS and charges and treat patients with
      more comorbidities compared to teaching hospitals. LOS, charges, and morbidity
      are directly proportional to hospital size. Urban hospitals have lower LOS and
      higher charges compared to rural hospitals. As hospital GB volume increases, LOS,
      charges, and morbidity decrease with no mortality effect. After controlling for
      all other covariates, male gender, increased age, and large hospital size were
      predictors of increased morbidity. Having had a complication predicted increased
      mortality, while female gender had a protective effect. Patient income, insurance
      status, and race did not play a role in morbidity or mortality. Neither academic,
      teaching status of the hospital or hospital gastric bypass volume influenced
      patient outcomes. Patient and hospital demographics do affect the outcomes of
      patients undergoing GB. Increasing age, male gender, and surgery performed in
      large hospitals are predictors of morbidity. Male gender and postoperative
      complications predict increased mortality. Neither comorbidities, race, payer,
      income, hospital academic status, location, nor hospital volume affect the
      outcome after GB.

PMID- 15943405
TI  - Idiopathic necrotizing fasciitis: risk factors and strategies for management.
AB  - The prognosis of necrotizing fasciitis (NF) depends on early diagnosis and
      management. Idiopathic NF may be more challenging, because it occurs in the
      absence of a known causative factor. Therefore, our purpose in this study was to
      identify the distinct features of idiopathic NF that may be important in early
      recognition of this disease and determine the factors associated with mortality.
      A retrospective chart review was performed in patients with a diagnosis of NF
      between 1988 and 2003. Patients were classified as idiopathic and secondary NF,
      and data were analyzed in terms of etiological and predisposing factors,
      causative microbiological organisms, and clinical outcome. The study included 98
      patients, 63 men and 35 women, with a diagnosis of NF. The median age was 55.5
      years (range, 13 - 80). Idiopathic NF occurred in 60 of 98 patients (61%). The
      principal anatomic sites of infection for NF were perineal localisation in 55
      patients (66%) and extremities in 31 patients (32%). Characteristics that
      distinguish patients with idiopathic NF from secondary NF were as follows: age
      older than 55 years (P = 0.0001), presence of comorbid illnesses like DM (P =
      0.007) or chronic renal failure (P = 0.041), and perineal localization (P =
      0.008). By logistic regression analysis, independent risk factors for idiopathic
      NF remained age > 55 years and perineal localization as statistically significant
      factors, when all the significant variables found in univariate analysis were
      included in the model. The majority of patients (82%) had polymicrobial
      infections. The mortality rate was 35 per cent. All patients were treated with
      radical surgical debridement and a combination of antibiotics. Female gender,
      presence of malignant disease, and diabetes mellitus (DM) were found to be
      associated with increased mortality as independent factors in logistic regression
      analysis, when all of these three factors were included in the model.
      Understanding the distinct clinical characteristics and the factors associated
      with mortality in patients with NF may lead to rapid diagnosis and improve the
      survival rates. Therefore, idiopathic NF is a crucial entity that requires
      serious suspicion for its diagnosis.

PMID- 15943406
TI  - Ten years of laparoscopic adrenalectomy: lesson learned from 104 procedures.
AB  - The purpose of this study was to evaluate the short- and long-term results of 104
      consecutive laparoscopic adrenalectomies performed during a period of 10 years in
      two specialist centers. One hundred four patients underwent laparoscopic
      adrenalectomy in two specialist centers in Italy between 1994 and 2003.
      Indications to laparoscopic adrenalectomy were aldosterone-secreting adenoma
      (20%), pheochromocytoma (24%), cortisol-secreting adenoma (11.5%), incidentaloma
      (26.9%), multiple endocrine neoplasia (MEN) type 2A (2.8%), adrenal metastases
      from lung cancer (3.8%), adrenal cyst (6.7%), and angiomyolipoma (3.8%).
      Transperitoneal anterior and lateral approaches were adopted in 17 and 84
      patients, respectively. Retroperitoneal approach was adopted in three patients.
      Mean operative time was 108 +/- 39.1 minutes (range, 40-300 minutes). There was
      no correlation between adrenal tumor diameter and operative time. Mean
      intraoperative blood loss was 106 mL (range, 40-600 mL). Intraoperative
      complication rate and conversion rate were 4.8 per cent (5 cases). Laparoscopic
      adrenalectomy is a safe procedure. After a relatively short learning curve, it
      can be performed successfully by any surgeon with low operative morbidity and
      mortality. The size of the adrenal tumor should not be considered a
      contraindication to this procedure.

PMID- 15943407
TI  - A prospective study comparing diathermy and scalpel incisions in tension-free
      inguinal hernioplasty.
AB  - Although still controversial, the use of diathermy instead of scalpel for skin
      incision and underlying tissue dissection is gradually gaining wide acceptance.
      This is due to the observation that no change in wound complication rates or
      postoperative pain are reported with the use of electrocautery. However, these
      studies include operations without the use of prosthetic materials during
      abdominal wall closure. The purpose of this study was to investigate the
      hypothesis that a) application of extreme heat may result in significant
      postoperative pain and poor wound healing because of excessive tissue damage and
      scarring respectively, and b) skin incision with the use of diathermy entails
      increased risk of wound infection in the presence of an underlying prosthetic
      material. One hundred twenty-five consecutive patients submitted to inguinal
      hernioplasty using the tension-free technique and fulfilling the inclusion
      criteria for the study were allocated alternately to either scalpel (n = 60), or
      diathermy (n = 57) groups. Eight patients had bilateral hernias. Five of them
      were allocated to the scalpel group and three to the diathermy group. According
      to the study protocol, they received both approaches for skin and underlying
      tissues incision, thus resulting in a total of 68 scalpel and 65 diathermy
      individual hernioplasties. Parameters measured included blood loss during the
      skin incision and underlying tissue dissection, postoperative pain and
      requirements for analgesics, the presence of wound dehiscence in the absence of
      infection, and postoperative wound infection on the day of discharge, on the day
      staples were removed, and 1 month after surgery. The two groups of patients were
      similar in relation to patient demographics, type of hernias, and operation
      details. Blood loss was minimal, and the amount of blood lost did not differ
      between the two groups. Diathermy group patients required less parenteral
      analgesics on the first postoperative day. A higher proportion of patients in the
      scalpel group continued to need oral analgesics on the second postoperative day
      compared to patients in the diathermy group. There was no difference between the
      two groups in terms of wound strength. Infectious complications were totally
      absent. The use of diathermy for skin incision during inguinal hernioplasty is as
      safe as the use of scalpel in terms of wound healing and reduces the analgesics
      requirements in the postoperative period.

PMID- 15943408
TI  - Metastatic choriocarcinoma to the pancreas.
AB  - Gestational choriocarcinoma is a highly metastatic neoplasm derived from
      placental tissue, occurring in approximately 1:20,000 - 40,000 pregnancies.
      Although gestational choriocarcinoma may follow any gestational event, it most
      commonly follows molar pregnancies. We report a case of a 24-year-old Hispanic
      woman with persistent trophoblastic disease who, after failing to respond to
      chemotherapy, was found to have metastasis to the liver and pancreas. The patient
      underwent successful distal pancreatectomy and splenectomy to be followed by
      salvage chemotherapy. Strong risk factors for choriocarcinoma include previous
      molar pregnancy or spontaneous abortion and increased maternal age. Gestational
      choriocarcinoma is classically responsive to chemotherapy; surgical excision is
      reserved for acute emergencies and is an acceptable option for patients with
      persistent disease in need of palliative treatment and tissue diagnosis.

PMID- 15943409
TI  - Upper gastrointestinal bleeding caused by a "hypophrenic" diverticulum of the
      distal esophagus.
AB  - Distal esophageal diverticula are uncommon acquired anomalies of the distal
      thoracic esophagus. We report a case of an elderly man presenting with a history
      of upper gastrointestinal bleeding secondary to a distal esophageal diverticulum
      arising from the intra-abdominal portion of the esophagus. To our knowledge, this
      is the first report of upper gastrointestinal bleeding from a subdiaphragmatic
      esophageal diverticulum. We propose the term "hypophrenic diverticulum of the
      esophagus" for this disease entity, and we would like to bring it to the
      attention of readers of The American Surgeon.

PMID- 15943410
TI  - APC, K-ras, and p53 gene mutations in colorectal cancer patients: correlation to
      clinicopathologic features and postoperative surveillance.
AB  - Current researches have proposed a genetic model for colorectal cancer (CRC), in
      which the sequential accumulation of mutations in specific cancer-related genes,
      including adenomatous polyposis coli (APC), K-ras, and p53, drives the transition
      from normal epithelium through increasing adenomatous dysplasia to colorectal
      cancer. To identify patients with an increased risk of tumor recurrence or
      metastasis and evaluate the prognostic values of APC, K-ras, and p53 gene
      mutations, we investigated the frequency of these three mutated genes in tumors
      and sera of CRC patients. APC, K-ras, and p53 gene mutations in primary tumor
      tissues and their paired preoperative serum samples of 118 CRC patients were
      detected by using polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) analysis, followed by direct DNA sequencing of the PCR
      amplified genomic DNA. Subsequently, serum molecular markers were analyzed for
      their correlation with patients' clinicopathologic features and presence of
      postoperative recurrence/metastasis. We did not observe any significant
      difference in the association of APC or K-ras or p53 gene mutations in primary
      tumors with patients' demographic data (all were P > 0.05). In contrast, both
      serum APC and p53 molecular markers were closely correlated with lymph node
      metastasis and TNM stage (both P < 0.05). Moreover, the serum overall molecular
      markers (at least one of the three markers) were prominently associated with
      depth of tumor invasion (P = 0.033), lymph node metastasis (P < 0.001), and TNM
      stage (P < 0.001). In addition, a significantly higher postoperative
      metastasis/recurrence rate in patients positive for overall molecular markers
      compared to those negative for these molecular markers were also demonstrated (P
      < 0.001). APC and K-ras molecular markers were more frequently observed in
      patients with locoregional metastasis (both P < 0.05), while p53 molecular marker
      was usually detected in the cases of peritoneal metastasis (P = 0.004). Our
      findings suggest that serum molecular markers are potentially useful in the
      determination of colorectal cancer patients harboring gene mutations at high risk
      of metastasis. Serial analysis is warranted in order to assess their long-term
      prognostic significance and the therapeutic implications.

PMID- 15943411
TI  - Role of leukocyte count, neutrophil percentage, and C-reactive protein in the
      diagnosis of acute appendicitis in the elderly.
AB  - Leukocyte count, neutrophil percentage, and C-reactive protein (CRP) have been
      shown to give valuable information in the diagnosis of acute appendicitis.
      However, whether these laboratory tests have the same clinical applicability in
      the elderly as in young patients remains unclear. This retrospective study aimed
      to clarify the role of these tests in the diagnosis of acute appendicitis in
      patients aged 60 years or over. Eighty-five consecutive elderly patients
      underwent appendectomy for suspected acute appendicitis during a 30-month period.
      Histologically verified appendicitis was found in 77 of the 85 patients (90.6%).
      There was no significant difference in leukocyte counts or CRP values between
      patients with acute appendicitis and those with a normal appendix. The
      sensitivities of leukocyte count, neutrophil percentage, and CRP in the diagnosis
      of acute appendicitis were 71.4 per cent, 88.3 per cent, and 90 per cent,
      respectively, while the specificities were 37.5 per cent, 25 per cent, and 37.5
      per cent, respectively. Of 77 patients with acute appendicitis, only two had all
      three tests simultaneously normal. In conclusion, patients with normal results in
      all three tests are highly unlikely to have acute appendicitis and should be
      evaluated with extra caution before surgery.

PMID- 15943412
TI  - Malignant transformation of a breast fibroadenoma to cystosarcoma phyllodes: case
      report and review of the literature.

PMID- 15943413
TI  - Major hepatobiliary surgery during pregnancy: safety and timing.
AB  - Hepatobiliary disease, although rare, may present during pregnancy with potential
      complications for mother and fetus. We present two cases of choledochal cysts and
      one case of a hepatic adenoma diagnosed in gravid patients. All three patients
      had acute events or failed medical management and were successfully treated with
      open resection, excision, or reconstruction during the second or third trimesters
      of pregnancy without requiring blood transfusions or tocolytic therapy. Although
      conservative treatment may be indicated in select patients due to the risk of
      underlying disease, we recommend surgical treatment preferably in the second
      trimester. With diligent intra- and postoperative management, pregnant patients
      can safely proceed with major hepatobiliary surgery.

PMID- 15943414
TI  - Falciform ligament hernia after laparoscopic cholecystectomy: a rare case and
      review of the literature.
AB  - The occurrence of an internal hernia through a congenital or iatrogenic defect in
      the falciform ligament is extremely rare. In the era of minimally invasive
      surgery, we present an unusual case of small bowel obstruction after laparoscopic
      cholecystectomy. An 85-year-old white male presented to the emergency room 2
      weeks after an uneventful cholecystectomy and complaining of a colicky,
      nonradiating right upper quadrant abdominal pain. Hydroxyiminodiacetic acid
      (HIDA) scan and endoscopic retrograde cholangiopancreatography (ERCP) performed
      revealed an open ductal system. Abdominal computed tomography (CT) scan was
      suggestive of a high-grade small bowel obstruction. Exploratory laparotomy
      revealed a herniated loop of distal ileum, passing from right to left through a
      defect in the falciform ligament created by the subxyphoid trochar. The surgeon
      should consider dividing the inferior leaf of the free edge of the falciform
      ligament, including the round ligament, should an aperture be created during
      laparoscopic port placement.

PMID- 15943415
TI  - Restorative proctocolectomy and ileal pouch-anal anastomosis for ulcerative
      colitis after liver transplant for primary sclerosing cholangitis: case report
      and review of literature.
AB  - Primary sclerosing cholangitis (PSC) is present in 5 per cent of patients with
      ulcerative colitis (UC). Conversely, as many as 90 per cent of patients with PSC
      have been found to have UC. The accepted treatment for advanced PSC is orthotopic
      liver transplant, and the treatment of ulcerative colitis with concomitant PSC is
      restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). A small
      number of studies have shown that there is an increased risk of pouchitis in UC
      patients with PSC after ileal pouch-anal anastomosis. We report a case of a 45
      year-old male who underwent a two-stage restorative proctocolectomy with IPAA
      after previous orthotopic liver transplant for PSC. We have reviewed the
      available literature concerning restorative proctocolectomy after liver
      transplantation, giving special attention to postoperative complications and
      subsequent development of pouchitis. It is important to be aware of the
      possibility of increased risk for development of pouchitis and to follow these
      patients closely to prevent complications.

PMID- 15943416
TI  - Recurrent intramucosal gastric carcinoma with extensive invasion to duodenal
      mucosa after endoscopic mucosal resection: a case report.
AB  - The occurrence of early gastric carcinoma with invasion to the duodenum is
      supposed to be very low, although advanced cancers arising in the antrum can
      often invade the duodenal area. Generally, malignant invasion of the duodenum is
      difficult to diagnose preoperatively, as spread of gastric cancer to the duodenum
      is often infiltrative and invades through the submucosal or subserosal layer. We
      report an unusual case of an intramucosal gastric carcinoma with extensive
      duodenal invasion that was preoperatively diagnosed by endoscopy.

PMID- 15943417
TI  - Combining multiple clusterings using evidence accumulation.
AB  - We explore the idea of evidence accumulation (EAC) for combining the results of
      multiple clusterings. First, a clustering ensemble--a set of object partitions,
      is produced. Given a data set (n objects or patterns in d dimensions), different
      ways of producing data partitions are: 1) applying different clustering
      algorithms and 2) applying the same clustering algorithm with different values of
      parameters or initializations. Further, combinations of different data
      representations (feature spaces) and clustering algorithms can also provide a
      multitude of significantly different data partitionings. We propose a simple
      framework for extracting a consistent clustering, given the various partitions in
      a clustering ensemble. According to the EAC concept, each partition is viewed as
      an independent evidence of data organization, individual data partitions being
      combined, based on a voting mechanism, to generate a new n x n, similarity matrix
      between the n patterns. The final data partition of the n patterns is obtained by
      applying a hierarchical agglomerative clustering algorithm on this matrix. We
      have developed a theoretical framework for the analysis of the proposed
      clustering combination strategy and its evaluation, based on the concept of
      mutual information between data partitions. Stability of the results is evaluated
      using bootstrapping techniques. A detailed discussion of an evidence accumulation
      based clustering algorithm, using a split and merge strategy based on the K-means
      clustering algorithm, is presented. Experimental results of the proposed method
      on several synthetic and real data sets are compared with other combination
      strategies, and with individual clustering results produced by well-known
      clustering algorithms.

PMID- 15943418
TI  - Edge-based identification of DP-features on free-form solids.
AB  - Numerous applications in mechanical CAD/CAM need robust algorithms for the
      identification of protrusion and depression features (DP-features) on geometric
      models with free-form (B-Spline) surfaces. This paper reports a partitioning
      algorithm that first identifies the boundary edges of DP-features and then
      creates a surface patch to cover the depressions or isolate the protrusions. The
      novelty of the method lies in the use of tangent continuity between edge segments
      to identify DP-feature boundaries that cross multiple faces and geometries.

PMID- 15943419
TI  - Evolutionary search for faces from line drawings.
AB  - Single 2D line drawing is a straightforward method to illustrate 3D objects. The
      faces of an object depicted by a line drawing give very useful information for
      the reconstruction of its 3D geometry. Two recently proposed methods for face
      identification from line drawings are based on two steps: finding a set of
      circuits that may be faces and searching for real faces from the set according to
      some criteria. The two steps, however, involve two combinatorial problems. The
      number of the circuits generated in the first step grows exponentially with the
      number of edges of a line drawing. These circuits are then used as the input to
      the second combinatorial search step. When dealing with objects having more
      faces, the combinatorial explosion prevents these methods from finding solutions
      within feasible time. This paper proposes a new method to tackle the face
      identification problem by a variable-length genetic algorithm with a novel
      heuristic and geometric constraints incorporated for local search. The hybrid GA
      solves the two combinatorial problems simultaneously. Experimental results show
      that our algorithm can find the faces of a line drawing having more than 30 faces
      much more efficiently. In addition, simulated annealing for solving the face
      identification problem is also implemented for comparison.

PMID- 15943420
TI  - Automatic sign language analysis: a survey and the future beyond lexical meaning.
AB  - Research in automatic analysis of sign language has largely focused on
      recognizing the lexical (or citation) form of sign gestures as they appear in
      continuous signing, and developing algorithms that scale well to large
      vocabularies. However, successful recognition of lexical signs is not sufficient
      for a full understanding of sign language communication. Nonmanual signals and
      grammatical processes which result in systematic variations in sign appearance
      are integral aspects of this communication but have received comparatively little
      attention in the literature. In this survey, we examine data acquisition, feature
      extraction and classification methods employed for the analysis of sign language
      gestures. These are discussed with respect to issues such as modeling transitions
      between signs in continuous signing, modeling inflectional processes, signer
      independence, and adaptation. We further examine works that attempt to analyze
      nonmanual signals and discuss issues related to integrating these with (hand)
      sign gestures. We also discuss the overall progress toward a true test of sign
      recognition systems--dealing with natural signing by native signers. We suggest
      some future directions for this research and also point to contributions it can
      make to other fields of research. Web-based supplemental materials (appendicies)
      which contain several illustrative examples and videos of signing can be found at
      www.computer.org/publications/dlib.

PMID- 15943421
TI  - Object-based image analysis using multiscale connectivity.
AB  - This paper introduces a novel approach for image analysis based on the notion of
      multiscale connectivity. We use the proposed approach to design several novel
      tools for object-based image representation and analysis which exploit the
      connectivity structure of images in a multiscale fashion. More specifically, we
      propose a nonlinear pyramidal image representation scheme, which decomposes an
      image at different scales by means of multiscale grain filters. These filters
      gradually remove connected components from an image that fail to satisfy a given
      criterion. We also use the concept of multiscale connectivity to design a
      hierarchical data partitioning tool. We employ this tool to construct another
      image representation scheme, based on the concept of component trees, which
      organizes partitions of an image in a hierarchical multiscale fashion. In
      addition, we propose a geometrically-oriented hierarchical clustering algorithm
      which generalizes the classical single-linkage algorithm. Finally, we propose two
      object-based multiscale image summaries, reminiscent of the well-known
      (morphological) pattern spectrum, which can be useful in image analysis and image
      understanding applications.

PMID- 15943422
TI  - Affine invariant pattern recognition using Multiscale Autoconvolution.
AB  - This paper presents a new affine invariant image transform called Multiscale
      Autoconvolution (MSA). The proposed transform is based on a probabilistic
      interpretation of the image function. The method is directly applicable to
      isolated objects and does not require extraction of boundaries or interest
      points, and the computational load is significantly reduced using the Fast
      Fourier Transform. The transform values can be used as descriptors for affine
      invariant pattern classification and, in this article, we illustrate their
      performance in various object classification tasks. As shown by a comparison with
      other affine invariant techniques, the new method appears to be suitable for
      problems where image distortions can be approximated with affine transformations.

PMID- 15943423
TI  - Identification of the defective transmission devices using the wavelet transform.
AB  - In this paper, a system is described that uses the wavelet transform to
      automatically identify the particular failure mode of a known defective
      transmission device. The problem of identifying a particular failure mode within
      a costly failed assembly is of benefit in practical applications. In this system,
      external acoustic sensors, instead of intrusive vibrometers, are used to record
      the acoustic data of the operating transmission device. A skilled factory worker,
      who is unfamiliar with statistical classification, helps to determine the feature
      vector of the particular failure mode in the feature extraction process. In the
      automatic identification part, an improved learning vector quantization (LVQ)
      method with normalizing the inputting feature vectors is proposed to compensate
      for variations in practical data. Some acoustic data, which are collected from
      the manufacturing site, are utilized to test the effectiveness of the described
      identification system. The experimental results show that this system can
      identify the particular failure mode of a defective transmission device and find
      out the causes of failure successfully.

PMID- 15943424
TI  - A two-stage linear discriminant analysis via QR-decomposition.
AB  - Linear Discriminant Analysis (LDA) is a well-known method for feature extraction
      and dimension reduction. It has been used widely in many applications involving
      high-dimensional data, such as image and text classification. An intrinsic
      limitation of classical LDA is the so-called singularity problems; that is, it
      fails when all scatter matrices are singular. Many LDA extensions were proposed
      in the past to overcome the singularity problems. Among these extensions,
      PCA+LDA, a two-stage method, received relatively more attention. In PCA+LDA, the
      LDA stage is preceded by an intermediate dimension reduction stage using
      Principal Component Analysis (PCA). Most previous LDA extensions are
      computationally expensive, and not scalable, due to the use of Singular Value
      Decomposition or Generalized Singular Value Decomposition. In this paper, we
      propose a two-stage LDA method, namely LDA/QR, which aims to overcome the
      singularity problems of classical LDA, while achieving efficiency and scalability
      simultaneously. The key difference between LDA/QR and PCA+LDA lies in the first
      stage, where LDA/QR applies QR decomposition to a small matrix involving the
      class centroids, while PCA+LDA applies PCA to the total scatter matrix involving
      all training data points. We further justify the proposed algorithm by showing
      the relationship among LDA/QR and previous LDA methods. Extensive experiments on
      face images and text documents are presented to show the effectiveness of the
      proposed algorithm.

PMID- 15943425
TI  - A theoretical and experimental analysis of linear combiners for multiple
      classifier systems.
AB  - In this paper, a theoretical and experimental analysis of linear combiners for
      multiple classifier systems is presented. Although linear combiners are the most
      frequently used combining rules, many important issues related to their operation
      for pattern classification tasks lack a theoretical basis. After a critical
      review of the framework developed in works by Tumer and Ghosh on which our
      analysis is based, we focus on the simplest and most widely used implementation
      of linear combiners, which consists of assigning a nonnegative weight to each
      individual classifier. Moreover, we consider the ideal performance of this
      combining rule, i.e., that achievable when the optimal values of the weights are
      used. We do not consider the problem of weights estimation, which has been
      addressed in the literature. Our theoretical analysis shows how the performance
      of linear combiners, in terms of misclassification probability, depends on the
      performance of individual classifiers, and on the correlation between their
      outputs. In particular, we evaluate the ideal performance improvement that can be
      achieved using the weighted average over the simple average combining rule and
      investigate in what way it depends on the individual classifiers. Experimental
      results on real data sets show that the behavior of linear combiners agrees with
      the predictions of our analytical model. Finally, we discuss the contribution to
      the state of the art and the practical relevance of our theoretical and
      experimental analysis of linear combiners for multiple classifier systems.

PMID- 15943426
TI  - Sparse multinomial logistic regression: fast algorithms and generalization
      bounds.
AB  - Recently developed methods for learning sparse classifiers are among the state-of
      the-art in supervised learning. These methods learn classifiers that incorporate
      weighted sums of basis functions with sparsity-promoting priors encouraging the
      weight estimates to be either significantly large or exactly zero. From a
      learning-theoretic perspective, these methods control the capacity of the learned
      classifier by minimizing the number of basis functions used, resulting in better
      generalization. This paper presents three contributions related to learning
      sparse classifiers. First, we introduce a true multiclass formulation based on
      multinomial logistic regression. Second, by combining a bound optimization
      approach with a component-wise update procedure, we derive fast exact algorithms
      for learning sparse multiclass classifiers that scale favorably in both the
      number of training samples and the feature dimensionality, making them applicable
      even to large data sets in high-dimensional feature spaces. To the best of our
      knowledge, these are the first algorithms to perform exact multinomial logistic
      regression with a sparsity-promoting prior. Third, we show how nontrivial
      generalization bounds can be derived for our classifier in the binary case.
      Experimental results on standard benchmark data sets attest to the accuracy,
      sparsity, and efficiency of the proposed methods.

PMID- 15943427
TI  - The angular difference function and its application to image registration.
AB  - The estimation of large motions without prior knowledge is an important problem
      in image registration. In this paper, we present the angular difference function
      (ADF) and demonstrate its applicability to rotation estimation. The ADF of two
      functions is defined as the integral of their spectral difference along the
      radial direction. It is efficiently computed using the pseudopolar Fourier
      transform, which computes the discrete Fourier transform of an image on a near
      spherical grid. Unlike other Fourier-based registration schemes, the suggested
      approach does not require any interpolation. Thus, it is more accurate and
      significantly faster.

PMID- 15943428
TI  - Video super-resolution using controlled subpixel detector shifts.
AB  - Video cameras must produce images at a reasonable frame-rate and with a
      reasonable depth of field. These requirements impose fundamental physical limits
      on the spatial resolution of the image detector. As a result, current cameras
      produce videos with a very low resolution. The resolution of videos can be
      computationally enhanced by moving the camera and applying super-resolution
      reconstruction algorithms. However, a moving camera introduces motion blur, which
      limits super-resolution quality. We analyze this effect and derive a theoretical
      result showing that motion blur has a substantial degrading effect on the
      performance of super-resolution. The conclusion is that, in order to achieve the
      highest resolution, motion blur should be avoided. Motion blur can be minimized
      by sampling the space-time volume of the video in a specific manner. We have
      developed a novel camera, called the "jitter camera," that achieves this
      sampling. By applying an adaptive super-resolution algorithm to the video
      produced by the jitter camera, we show that resolution can be notably enhanced
      for stationary or slowly moving objects, while it is improved slightly or left
      unchanged for objects with fast and complex motions. The end result is a video
      that has a significantly higher resolution than the captured one.

PMID- 15943429
TI  - Motion segmentation using occlusions.
AB  - We examine the key role of occlusions in finding independently moving objects
      instantaneously in a video obtained by a moving camera with a restricted field of
      view. In this problem, the image motion is caused by the combined effect of
      camera motion (egomotion), structure (depth), and the independent motion of scene
      entities. For a camera with a restricted field of view undergoing a small motion
      between frames, there exists, in general, a set of 3D camera motions compatible
      with the observed flow field even if only a small amount of noise is present,
      leading to ambiguous 3D motion estimates. If separable sets of solutions exist,
      motion-based clustering can detect one category of moving objects. Even if a
      single inseparable set of solutions is found, we show that occlusion information
      can be used to find ordinal depth, which is critical in identifying a new class
      of moving objects. In order to find ordinal depth, occlusions must not only be
      known, but they must also be filled (grouped) with optical flow from neighboring
      regions. We present a novel algorithm for filling occlusions and deducing ordinal
      depth under general circumstances. Finally, we describe another category of
      moving objects which is detected using cardinal comparisons between structure
      from motion and structure estimates from another source (e.g., stereo).

PMID- 15943431
TI  - Fast unambiguous stereo matching using reliability-based dynamic programming.
AB  - An efficient unambiguous stereo matching technique is presented in this paper.
      Our main contribution is to introduce a new reliability measure to dynamic
      programming approaches in general. For stereo vision application, the reliability
      of a proposed match on a scanline is defined as the cost difference between the
      globally best disparity assignment that includes the match and the globally best
      assignment that does not include the match. A reliability-based dynamic
      programming algorithm is derived accordingly, which can selectively assign
      disparities to pixels when the corresponding reliabilities exceed a given
      threshold. The experimental results show that the new approach can produce dense
      (> 70 percent of the unoccluded pixels) and reliable (error rate < 0.5 percent)
      matches efficiently (< 0.2 sec on a 2GHz P4) for the four Middlebury stereo data
      sets.

PMID- 15943430
TI  - Offline geometric parameters for automatic signature verification using fixed
      point arithmetic.
AB  - This paper presents a set of geometric signature features for offline automatic
      signature verification based on the description of the signature envelope and the
      interior stroke distribution in polar and Cartesian coordinates. The features
      have been calculated using 16 bits fixed-point arithmetic and tested with
      different classifiers, such as hidden Markov models, support vector machines, and
      Euclidean distance classifier. The experiments have shown promising results in
      the task of discriminating random and simple forgeries.

PMID- 15943432
TI  - Continued growth of single-walled carbon nanotubes.
AB  - We demonstrate the continued growth of single-walled carbon nanotubes (SWNTs)
      from ordered arrays of open-ended SWNTs in a way analogous to epitaxy. Nanometer
      sized metal catalysts were docked to the SWNT open ends and subsequently
      activated to restart growth. SWNTs thus grown inherit the diameters and chirality
      from the seeded SWNTs, as indicated by the closely matched frequencies of Raman
      radial breathing modes before and after the growth.

PMID- 15943434
TI  - Light scattering of ultrafine silica particles by VUV synchrotron radiation.
AB  - Vacuum ultraviolet (VUV) light scattering from ultrafine silica particles is
      studied with an aerosol instrument recently established at the Advanced Light
      Source (ALS) in Berkeley. Silica particles, size-selected by a differential
      mobility analyzer, are introduced into vacuum through a set of aerodynamic lenses
      to form a particle beam. The scattered photons from the crossing area of the VUV
      synchrotron beam and particle beam are detected with a rotatable VUV photon
      detector. The angular distributions of scattered photons (ADSP) originating from
      70, 100, 200 nm diameter silica particles are measured with 145.9 and 118.1 nm
      synchrotron radiation. These angular distributions show strong forward
      scattering. The measured ADSPs are consistent with simulation of Mie scattering.
      The refractive indices of silica particles, 2.6 + 1.1i and 1.6 + 0.0001i for
      118.1 and 145.9 nm, respectively, are obtained by fitting the measured ADSPs; the
      least average percentage deviations are 18% and 6%, respectively. The scattered
      fluxes at widely different wavelengths (visible versus VUV) also exhibit clear
      size sensitivity. Under comparable experimental conditions of photon fluxes and
      detection efficiencies, limits of particle size detection of 70 and 250 nm are
      obtained, respectively, when using 118.1 and 532 nm illumination. As anticipated,
      VUV scattering is a more sensitive probe for ultrafine particles, which will find
      application in detection of these ubiquitous species beyond the confines of a
      laboratory.

PMID- 15943433
TI  - Optical and MRI multifunctional nanoprobe for targeting gliomas.
AB  - A multifunctional nanoprobe capable of targeting glioma cells, detectable by both
      magnetic resonance imaging and fluorescence microscopy, was developed. The
      nanoprobe was synthesized by coating iron oxide nanoparticles with covalently
      bound bifunctional poly(ethylene glycol) (PEG) polymer, which were subsequently
      functionalized with chlorotoxin and the near-infrared fluorescing molecule Cy5.5.
      Both MR imaging and fluorescence microscopy showed significant preferential
      uptake of the nanoparticle conjugates by glioma cells. Such a nanoprobe could
      potentially be used to image resections of glioma brain tumors in real time and
      to correlate preoperative diagnostic images with intraoperative pathology at
      cellular-level resolution.

PMID- 15943435
TI  - Curvature induced L-defects in water conduction in carbon nanotubes.
AB  - We conduct molecular dynamics simulations to study the effect of the curvature
      induced static dipole moment of small open-ended single-walled carbon nanotubes
      (CNTs) immersed in water. This dipole moment generates a nonuniform electric
      field, changing the energy landscape in the CNT and altering the water conduction
      process. The CNT remains practically filled with water at all times, whereas
      intermittent filling is observed when the dipole term is not included. In
      addition, the dipole moment induces a preferential orientation of the water
      molecules near the end regions of the nanotube, which in turn causes a
      reorientation of the water chain in the middle of the nanotube. The most
      prominent feature of this reorientation is an L-defect in the chain of water
      molecules inside the CNT. The analysis of the water energetics and structural
      characteristics inside and in the vicinity of the CNT helps to identify the role
      of the dipole moment and to suggest possible mechanisms for controlled water and
      proton transport at the nanoscale.

PMID- 15943436
TI  - Novel integrated electrochemical nano-biochip for toxicity detection in water.
AB  - An electrochemical nano-biochip for water toxicity detection is presented. We
      describe chip design, fabrication, and performance. Bacteria, which have been
      genetically engineered to respond to environmental stress, act as a sensor
      element and trigger a sequence of processes, which leads to generation of
      electrical current. This novel, portable and miniature device provides rapid and
      sensitive real-time electrochemical detection of acute toxicity in water. A clear
      signal is produced within less than 10 min of exposure to various concentrations
      of toxicants, or to stress conditions, with a direct correlation between the
      toxicant concentration and the induced current.

PMID- 15943437
TI  - Size dependent breakdown of superconductivity in ultranarrow nanowires.
AB  - Below a certain temperature T(c) (typically cryogenic), some materials lose their
      electric resistance R entering a superconducting state. Following the general
      trend toward a large scale integration of a greater number of electronic
      components, it is desirable to use superconducting elements in order to minimize
      heat dissipation. It is expected that the basic property of a superconductor,
      i.e., dissipationless electric current, will be preserved at reduced scales
      required by modern nanoelectronics. Unfortunately, there are indications that for
      a certain critical size limit of the order of approximately 10 nm, below which a
      "superconducting" nanowire is no longer a superconductor in a sense that it
      acquires a finite resistance even at temperatures close to absolute zero. In the
      present paper we report experimental evidence for a superconductivity breakdown
      in ultranarrow quasi-1D aluminum nanowires.

PMID- 15943438
TI  - Co-continuous metal-ceramic nanocomposites.
AB  - A room temperature technique was developed to produce continuous metal nanowires
      embedded in random nanoporous ceramic skeletons. The synthesis involves
      preparation of uniform, nanoporous ceramic pre-forms and subsequent
      electrochemical metal infiltration at room temperature, so to avoid material
      incompatibilities frequently encountered in traditional high-temperature liquid
      metal infiltration. Structure and preliminary evaluations of mechanical and
      electronic properties of copper/alumina nanocomposites are reported.

PMID- 15943439
TI  - Multicolor light-emitting diodes based on semiconductor nanocrystals encapsulated
      in GaN charge injection layers.
AB  - Numerous technologies including solid-state lighting, displays, and traffic
      signals can benefit from efficient, color-selectable light sources that are
      driven electrically. Semiconductor nanocrystals are attractive types of
      chromophores that combine size-controlled emission colors and high emission
      efficiencies with excellent photostability and chemical flexibility. Applications
      of nanocrystals in light-emitting technologies, however, have been significantly
      hindered by difficulties in achieving direct electrical injection of carriers.
      Here we report the first successful demonstration of electroluminescence from an
      all-inorganic, nanocrystal-based architecture in which semiconductor nanocrystals
      are incorporated into a p-n junction formed from GaN injection layers. The
      critical step in the fabrication of these nanocrystal/GaN hybrid structures is
      the use of a novel deposition technique, energetic neutral atom beam
      lithography/epitaxy, that allows for the encapsulation of nanocrystals within a
      GaN matrix without adversely affecting either the nanocrystal integrity or its
      luminescence properties. We demonstrate electroluminescence (injection
      efficiencies of at least 1%) in both single- and two-color regimes using
      structures comprising either a single monolayer or a bilayer of nanocrystals.

PMID- 15943440
TI  - Bundling up carbon nanotubes through Wigner defects.
AB  - We show, using ab initio total energy density functional theory, that the so
      called Wigner defects, an interstitial carbon atom right beside a vacancy, which
      are present in irradiated graphite, can also exist in bundles of carbon
      nanotubes. Due to the geometrical structure of a nanotube, however, this defect
      has a rather low formation energy, lower than the vacancy itself, suggesting that
      it may be one of the most important defects that are created after electron or
      ion irradiation. Moreover, they form a strong link between the nanotubes in
      bundles, increasing their shear modulus by a sizable amount, clearly indicating
      its importance for the mechanical properties of nanotube bundles.

PMID- 15943441
TI  - Amplified electrocatalysis at DNA-modified nanowires.
AB  - Arrayed gold nanowires are a novel and useful platform for electrochemical DNA
      detection. Pilot studies testing the use of these templated structures with an
      electrocatalytic reporter system revealed that very low detection thresholds for
      target DNA sequences can be obtained. One factor contributing to the heightened
      sensitivity is the high signal-to-noise ratio achieved with the large
      electrocatalytic signals observed at DNA-modified nanowires. Here, we explain the
      improved sensitivity with evidence illustrating that electrocatalysis at DNA
      modified nanostructures generates amplified signals that are significantly larger
      than those observed at bulk gold surfaces. The results presented strongly suggest
      that the three-dimensional architectures of the nanowires facilitate the
      electrocatalytic reaction because of enhanced diffusion occurring around these
      structures. Effects unique to the nanoscale are shown to underlie the utility of
      nanowires for DNA biosensing.

PMID- 15943442
TI  - Single molecular orientation switching of an endohedral metallofullerene.
AB  - The single molecular orientation switching of the Tb@C82 endohedral
      metallofullerene has been studied by using low-temperature ultrahigh vacuum (UHV)
      scanning tunneling microscopy (STM). An octanethiol self-assembled monolayer
      (SAM) was introduced between Tb@C82 and the Au111 substrate to control the
      thermal rotational states of Tb@C82. Scanning tunneling spectroscopy (STS) of
      Tb@C82 on an octanethiol SAM at 13 K demonstrated hysteresis including negative
      differential conductance (NDC). This observed hysteresis and NDC is interpreted
      in terms of a switching of the Tb@C82 molecular orientation caused by the
      interaction between its electric dipole moment and an external electric field.

PMID- 15943443
TI  - Supramolecular nanostamping: using DNA as movable type.
AB  - Here we present a novel printing technique (that we call supramolecular
      nanostamping), based on the replication of single-stranded DNA features through a
      hybridization-contact-dehybridization cycle. On a surface containing features
      each made of single-stranded DNA molecules of known sequence, the complementary
      DNA molecules are hybridized, spontaneously assembling onto the original pattern
      due to sequence-specific interactions. These complementary DNA strands, on the
      end that is assembled far from the original surface, are 5' modified with
      chemical groups ("sticky ends") that can form bonds with a target surface that is
      brought into contact. Heating induces dehybridization between DNA strands,
      leaving the original pattern on the original surface and the copied pattern on
      the secondary substrate, and thus stamping (see Figure 1). Molecular recognition
      provides the unique and disruptive ability of transferring large amounts of
      information in a single printing cycle, that is the simultaneous stamping of
      spatial information (i.e., the patterns) and of chemical information (i.e., the
      features' DNA sequence--their chemical composition). This method combines high
      resolution (<40 nm) with the advantage of an exponential increase in the number
      of masters; in fact, any printed substrate can be reused as a master. Patterns
      fabricated via very different lithographic techniques can be replicated.

PMID- 15943444
TI  - Controlling plasmon line shapes through diffractive coupling in linear arrays of
      cylindrical nanoparticles fabricated by electron beam lithography.
AB  - The effect of diffractive coupling on the collective plasmon line shape of linear
      arrays of Ag nanoparticles fabricated by electron beam lithography has been
      investigated using Rayleigh scattering spectroscopy. The array spectra exhibit an
      intricate multi-peak structure, including a narrow mode that gains strength for
      interparticle distances that are close to the single particle resonance
      wavelength. A version of the discrete dipole approximation method provides an
      excellent qualitative description of the observed behavior.

PMID- 15943445
TI  - Nanowire lithography: fabricating controllable electrode gaps using Au-Ag-Au
      nanowires.
AB  - A method to fabricate nanowire electrodes possessing controllable gaps is
      described. The method relies on electrochemical deposition and selective chemical
      etching or heating to selectively remove the Ag segment of Au-Ag-Au nanowires.
      Because the thickness of the Ag segment directly dictates the size of the
      nanogap, the gap width can be easily controlled during the nanowire fabrication
      process. Herein, we demonstrate gaps with 2 microm, 100 nm and 20 nm widths via
      the above-mentioned approaches. In addition, we observed that small gaps
      (approximately 20 nm) can be formed through annealing Au-Ag-Au nanowires at 200
      degrees C in air. Electrical contact between nanowire electrodes and contact pads
      is studied. Using nanowire electrodes with a 100 nm gap, we subsequently
      fabricate organic field effect transistors (FETs) with regioregular poly(3
      hexylthiophene).

PMID- 15943446
TI  - Polyaniline nanofiber/gold nanoparticle nonvolatile memory.
AB  - A nonvolatile plastic digital memory device based on nanofibers of the conjugated
      polymer polyaniline decorated with gold nanoparticles is reported. The device has
      a simple structure consisting of the plastic composite film sandwiched between
      two electrodes. An external bias is used to program the ON and OFF states of the
      device that are separated by a 3-orders-of-magnitude difference in conductivity.
      ON-OFF switching times of less than 25 ns are observed by electrical pulse
      measurements. The devices possess prolonged retention times of several days after
      they have been programmed. Write-read-erase cycles are also demonstrated. The
      switching mechanism is attributed to an electric-field-induced charge transfer
      from the polyaniline nanofibers to the gold nanoparticles. The active polymer
      layer is created by growing nanometer size gold particles within 30-nm-diameter
      polyaniline nanofibers using a redox reaction with chloroauric acid. This device
      combines two exciting research areas--nanoparticles and conducting polymers--to
      form a novel materials system with unique functionality.

PMID- 15943447
TI  - Stranski-Krastanow growth of germanium on silicon nanowires.
AB  - There have been extensive studies of germanium (Ge) grown on planar silicon (Si)
      substrates by the Stranski-Krastanow (S-K) mechanism. In this study, we present S
      K growth of Ge on Si nanowires. The Si nanowires were grown at 500 degrees C by a
      vapor-liquid-solid (VLS) method, using silane (SiH4) as the gaseous precursor. By
      switching the gas source from SiH4 to germane (GeH4) during the growth and
      maintaining the growth conditions, epitaxial Ge islands deposited on the outer
      surface of the initially formed Si nanowires. Transmission electron microscopy
      (TEM), scanning TEM, and energy-dispersive X-ray spectroscopy techniques were
      utilized to identify the thin wetting layer and the three-dimensional Ge islands
      formed around the Si core nanowires. Cross-sectional TEM verified the surface
      faceting of the Si core nanowires as well as the Ge islands.

PMID- 15943448
TI  - Integration of scanning probes and ion beams.
AB  - We report the integration of a scanning force microscope with ion beams. The
      scanning probe images surface structures non-invasively and aligns the ion beam
      to regions of interest. The ion beam is transported through a hole in the
      scanning probe tip. Piezoresistive force sensors allow placement of micromachined
      cantilevers close to the ion beam lens. Scanning probe imaging and alignment is
      demonstrated in a vacuum chamber coupled to the ion beam line. Dot arrays are
      formed by ion implantation in resist layers on silicon samples with dot diameters
      limited by the hole size in the probe tips of a few hundred nm.

PMID- 15943449
TI  - Quantum transport through a DNA wire in a dissipative environment.
AB  - Electronic transport through DNA wires in the presence of a strong dissipative
      environment is investigated. We show that new bath-induced electronic states are
      formed within the band gap. These states show up in the linear conductance
      spectrum as a temperature dependent background and lead to a crossover from
      tunneling to thermal activated behavior with increasing temperature. Depending on
      the strength of the electron-bath coupling, the conductance at the Fermi level
      can show a weak exponential or even an algebraic length dependence. Our results
      suggest a new environmentally induced transport mechanism. This might be relevant
      for the understanding of molecular conduction experiments in liquid solution,
      such as those recently performed on poly(GC) oligomers in a water buffer (B. Xu
      et al., Nano Lett. 2004, 4, 1105).

PMID- 15943450
TI  - Atomic nanotube welders: boron interstitials triggering connections in double
      walled carbon nanotubes.
AB  - Here we demonstrate that the incorporation of boron (B) atoms between double
      walled carbon nanotubes (DWNTs) during thermal annealing (1400-1600 degrees C)
      results in covalent nanotube "Y" junctions, DWNT coalescence, and the formation
      of flattened multiwalled carbon nanotubes (MWNTs). These processes occur via the
      merging of adjacent tubes, which is triggered by B interstitial atoms. We observe
      that B atom interstitials between DWNTs are responsible for the rapid
      establishment of covalent connections between neighboring tubes (polymerization),
      thereby resulting in the fast annealing of the carbon cylinders with B atoms
      embedded in the newly created carbon nanotube network. Once B is in the lattice,
      tube faceting (polygonization) starts to occur, and the electronic properties are
      expected to change dramatically. Therefore, B atoms indeed act as atomic nanotube
      fusers (or welders), and this process could now be used in assembling novel
      electronic nanotube devices, nanotube networks, carbon nanofoams and
      heterojunctions exhibiting p-type electronic properties.

PMID- 15943451
TI  - Carbon nanotube substrates boost neuronal electrical signaling.
AB  - We demonstrate the possibility of using carbon nanotubes (CNTs) as potential
      devices able to improve neural signal transfer while supporting dendrite
      elongation and cell adhesion. The results strongly suggest that the growth of
      neuronal circuits on a CNT grid is accompanied by a significant increase in
      network activity. The increase in the efficacy of neural signal transmission may
      be related to the specific properties of CNT materials, such as the high
      electrical conductivity.

PMID- 15943452
TI  - Thermal conductivity modeling of core-shell and tubular nanowires.
AB  - The heteroepitaxial growth of crystalline core-shell nanostructures of a variety
      of materials has become possible in recent years, allowing the realization of
      various novel nanoscale electronic and optoelectronic devices. The increased
      surface or interface area will decrease the thermal conductivity of such
      nanostructures and impose challenges for the thermal management of such devices.
      In the meantime, the decreased thermal conductivity might benefit the
      thermoelectric conversion efficiency. In this paper, we present modeling results
      on the lattice thermal conductivity of core-shell and tubular nanowires along the
      wire axis direction using the phonon Boltzmann equation. We report the dependence
      of the thermal conductivity on the surface conditions and the core-shell geometry
      for silicon core-germanium shell and tubular silicon nanowires at room
      temperature. The results show that the effective thermal conductivity changes not
      only with the composition of the constituents but also with the radius of the
      nanowires and nanopores due to the nature of the ballistic phonon transport. The
      results in this work have implications for the design and operation of a variety
      of nanoelectronic devices, optoelectronic devices, and thermoelectric materials
      and devices.

PMID- 15943453
TI  - High rectifying efficiencies of microtubule motility on kinesin-coated gold
      nanostructures.
AB  - We demonstrate highly efficient rectification of microtubule motility on gold
      nanofabricated structures. First, we present a novel nanofabrication process for
      the creation of gold tracks for microtubule motility recessed in silicon oxide.
      This approach is particularly useful because it enables the use of the well
      understood PEG-silane chemistry on SiO2 for the blocking of kinesin, whereas the
      gold tracks allow possible electrical control. We demonstrate excellent
      confinement of microtubule motility to the gold nanostructures and that
      microtubules move on the gold with speeds comparable to that on glass. Second, we
      present designs of three advanced rectifier geometries. We analyze the
      microtubule pathways through the geometries, and we demonstrate highly efficient
      rectification with up to 92% efficiency. As a result, we find that up to 97% of
      the microtubules move unidirectionally.

PMID- 15943454
TI  - Femtosecond imaging of surface plasmon dynamics in a nanostructured silver film.
AB  - Light interacting with nanostructured metals excites the collective charge
      density fluctuations known as surface plasmons (SP). Through excitation of the
      localized SP eigenmodes incident light is trapped on the nanometer spatial and
      femtosecond temporal scales and its field is enhanced. Here we demonstrate the
      imaging and quantum control of SP dynamics in a nanostructured silver film. By
      inducing and imaging the nonlinear two-photon photoemission from the sample with
      a pair of identical 10-fs laser pulses while scanning the pulse delay, we record
      a movie of SP fields at a rate of 330-attoseconds/frame.

PMID- 15943455
TI  - Parallel fabrication of sub-50-nm uniformly sized nanoparticles by deposition
      through a patterned silicon nitride nanostencil.
AB  - Using low-pressure chemical vapor deposition of silicon dioxide, we have reduced
      the size of 56-nm features in a silicon nitride membrane, called a stencil, down
      to 36 nm. Sub-50-nm uniformly sized nanoparticles are fabricated by electron-beam
      deposition of Pt through the stencil mask. A self-assembled monolayer (SAM) of
      tridecafluoro-1,1,2,2-tetrahydrooctyl-1-trichlorosilane was used to reduce Pt
      clogging of the nanosize holes during deposition as well as to protect the
      stencil during the postdeposition Pt removal. X-ray photoelectron spectroscopy
      shows that the SAM protects the stencil efficiently during this postdeposition
      removal of Pt.

PMID- 15943456
TI  - Controlled switching of optical emission energies in semiconducting single-walled
      carbon nanotubes.
AB  - We present scanning photoluminescence (PL) microscopy of freely suspended single
      walled carbon nanotubes grown by chemically assisted vapor deposition (CVD)
      across micron-sized open apertures. Scans of the PL emission versus excitation
      position show unusual "holes"having subwavelength spatial features associated
      with abrupt blue shifts of the emission energy. By varying the excitation
      polarization, energy, intensity, and position, we demonstrate that optical
      switching in some nanotubes is controllable in a highly nonlinear manner by
      adjusting the nonequilibrium carrier density in the nanotube. Technologically
      important attributes include large spectral contrast between on/off states at
      room temperature, a dramatic response to small changes in light intensity near
      threshold, and the possibility that electrical charge injection could also be
      used to control emission energies.

PMID- 15943457
TI  - Highly efficient multiphoton-absorption-induced luminescence from gold
      nanoparticles.
AB  - We demonstrate that highly efficient photoluminescence is generated from gold
      nanoparticles as small as a few nanometers in diameter upon irradiation with sub
      100-fs pulses of 790-nm light. Strong emission is observed at excitation
      intensities comparable to or less than those typically used for multiphoton
      imaging of fluorescently labeled biological samples. The particles have polarized
      emission, can radiate more efficiently than single molecules, do not exhibit
      significant blinking, and are photostable under hours of continuous excitation.
      These observations suggest that metal nanoparticles are a viable alternative to
      fluorophores or semiconductor nanoparticles for biological labeling and imaging.

PMID- 15943458
TI  - Coherent single charge transport in molecular-scale silicon nanowires.
AB  - We report low-temperature electrical transport studies of chemically synthesized,
      molecular-scale silicon nanowires. Individual nanowires exhibit Coulomb blockade
      oscillations characteristic of charge addition to a single nanostructure on
      length scales up to at least 400 nm. Studies also demonstrate coherent charge
      transport through discrete single particle quantum levels extending across whole
      devices, and show that the ground-state spin configuration is consistent with the
      constant interaction model. In addition, depletion of nanowires suggests that
      phase coherent single-dot characteristics are accessible in the few-charge
      regime. These results differ from those for nanofabricated planar silicon
      devices, which show localization on much shorter length scales, and thus suggest
      potential for molecular-scale silicon nanowires as building blocks for quantum
      and conventional electronics.

PMID- 15943459
TI  - Ionic transport phenomena in nanofluidics: experimental and theoretical study of
      the exclusion-enrichment effect on a chip.
AB  - In nanometer-sized apertures with charged surfaces, the extension of the
      electrical double layer results in the electrostatic exclusion of co-ions and
      enrichment in counterions, which affects the permselectivity of such structures.
      A modeling of this phenomenon is proposed and is compared with quantitative
      measurements of the ionic permeability change of a Pyrex nanoslit at low ionic
      strength. The comparison of experimental results with theoretical predictions
      justifies that electrostatic forces are the governing forces in nanofluidics.

PMID- 15943460
TI  - Nanometer patterning with ice.
AB  - Nanostructures can be patterned with focused electron or ion beams in thin,
      stable, conformal films of water ice grown on silicon. We use these patterns to
      reliably fabricate sub-20 nm wide metal lines and exceptionally well-defined, sub
      10 nanometer beam-induced chemical surface transformations. We argue more
      generally that solid-phase condensed gases of low sublimation energy are ideal
      materials for nanoscale patterning, and water, quite remarkably, may be among the
      most useful.

PMID- 15943461
TI  - Nanolithography based on the formation and manipulation of nanometer-size organic
      liquid menisci.
AB  - Nanometer-size menisci of organic liquids such as octane and 1-octene have been
      formed and used to confine chemical reactions. The application of a bias voltage
      between a conductive scanning probe tip separated a few nanometers from a silicon
      surface allows the field-induced formation of nanometer-size liquid menisci that
      can subsequently be used to fabricate nanometer-size structures. We report the
      fabrication of sub-10-nm nanostructures in 0.1 ms. Growth kinetics studies reveal
      that the nanostructure composition and its formation mechanism are organic
      solvent-dependent. Both voltage polarities can be used to grow nanostructures,
      although the growth rate is significantly higher for positively biased samples.
      These experiments allow us to produce in the same sample two chemically different
      nanostructures that are easily addressed and positioned and have sub-10-nm
      features.

PMID- 15943462
TI  - Electromechanical instability in suspended carbon nanotubes.
AB  - We have theoretically investigated electromechanical properties of freely
      suspended carbon nanotubes when a current is injected into the tubes using a
      scanning tunneling microscope. We show that a shuttle-like electromechanical
      instability can occur if the bias voltage exceeds a dissipation-dependent
      threshold value. An instability results in large amplitude vibrations of the
      carbon nanotube bending mode, which modify the current-voltage characteristics of
      the system.

PMID- 15943463
TI  - Preparation of fullerene-shell dendrimer-core nanoconjugates.
AB  - Generation 4 amine-terminated polyamidoamine dendrimer (PAMAM G4) was allowed to
      react with an excess of buckminsterfullerene (C60) to form a nanoconjugate
      containing a PAMAM core and C60 shell. The PAMAM-C60 conjugate was characterized
      by MALDI-TOF, TGA, UV-vis, and IR spectroscopy. Approximately thirty shell
      fullerenes surround each dendrimer core. The conjugates catalyze photooxidation
      of thioanisole by generation of singlet oxygen (1O2). The oxidation reactions
      occur in both organic and aqueous solvents, but the reactivity is enhanced in
      aqueous solution, possibly due to a nanoreactor effect resulting from diffusion
      of hydrophobic reactant molecules into dendrimer cavities.

PMID- 15943464
TI  - Combined optical tweezers/ion beam technique to tune colloidal masks for
      nanolithography.
AB  - A method is presented to control the in-plane ordering, size, and interparticle
      distance of nanoparticles fabricated by evaporation through a mask of colloidal
      particles. The use of optical tweezers combined with critical point drying gives
      single-particle position control over the colloidal particles in the mask. This
      extends the geometry of the colloidal masks from (self-organized) hexagonal to
      any desired symmetry and spacing. Control over the mask's hole size is achieved
      by MeV ion irradiation, which causes the colloids to expand in the in-plane
      direction, thus shrinking the size of the holes. After modification of the mask,
      evaporation at different angles with respect to the mask gives additional control
      over structure and interparticle distance, allowing nanoparticles of different
      materials to be deposited next to each other. We demonstrate large arrays of
      metal nanoparticles with dimensions in the 15-30 nm range, with control over the
      interparticle distance and in-plane ordering.

PMID- 15943465
TI  - Functional reconstitution of protein ion channels into planar polymerizable
      phospholipid membranes.
AB  - We demonstrate that polymerizable planar membranes permit reconstitution of
      protein ion channels formed by the bacterial toxins Staphylococcus aureus alpha
      hemolysin (alphaHL) and Bacillus anthracis protective antigen 63. The alphaHL
      channel remained functional even after membrane polymerization. Surface pressure
      measurements suggest that the ease of forming membranes depends on membrane
      surface elasticity estimated from Langmuir-Blodgett monolayer pressure-area
      isotherms. The ability to stabilize nanoscale pores in robust ultrathin films may
      prove useful in single molecule sensing applications.

PMID- 15943466
TI  - Metal nanoshell assembly on a virus bioscaffold.
AB  - Chilo iridescent virus is demonstrated as a useful core substrate in the
      fabrication of metallodielectric, plasmonic nanostructures. A gold shell is
      assembled around the wild-type viral core by attaching small, 2-5-nm gold
      nanoparticles to the virus surface by means of the chemical functionality found
      inherently on the surface of the proteinaceous viral capsid. The density of these
      nucleation sites was maximized by reducing the repulsive forces between the gold
      particles through electrolyte addition. These gold nanoparticles then act as
      nucleation sites for the electroless deposition of gold ions from solution around
      the biotemplate. The optical extinction spectra of the metalloviral complex is in
      quantitative agreement with Mie scattering theory. Overall, the utilization of a
      native virus and the inherent chemical functionality of the capsid afford the
      ability to grow and harvest biotemplates for metallodielectric nanoshells in
      large quantities, potentially providing cores with a narrower size distribution
      and smaller diameters (below 80 nm) than for currently used silica.

PMID- 15943467
TI  - Modification of the estrogenic properties of diphenols by the incorporation of
      ferrocene. Generation of antiproliferative effects in vitro.
AB  - We report here the synthesis and the strong and unexpected antiproliferative
      effect of the organometallic diphenolic compound 1,1-bis(4'-hydroxyphenyl)-2
      ferrocenyl-but-1-ene (4) on both hormone-dependent (MCF7) and -independent (MDA
      MB231) breast cancer cells (IC(50) = 0.7 and 0.6 microM). Surprisingly, 6 [1,2
      bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene], the regioisomer of 4, shows only a
      modest effect on these cell lines. This pertinent organometallic modification
      seems to trigger an intracellular oxidation of the structurally favorable
      compound 4, leading to the generation of a potent cytotoxic compound.

PMID- 15943468
TI  - Potent estrogen receptor ligands based on bisphenols with a globular hydrophobic
      core.
AB  - Candidate estrogen receptor (ER) ligands with two phenolic residues on a three
      dimensional hydrophobic core structure (carborane, bicyclo[2.2.2]octene, or
      adamantane) were synthesized and biologically evaluated. The biological
      properties of the ligands were markedly dependent on the nature of the
      hydrophobic core structure. Bis(4-hydroxyphenyl)-o-carborane (6) was a partial
      agonist/antagonist for ER. 1,2-Bis(4-hydroxyphenyl)bicyclo[2.2.2]octene (10)
      exhibited potent agonist activity for ER, even though the two phenolic groups are
      located similarly to those of 6.

PMID- 15943469
TI  - Examination of phosphoryl-mimicking functionalities within a macrocyclic Grb2 SH2
      domain-binding platform.
AB  - Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities
      of several phosphoryl-mimicking groups displayed within the context of a
      conformationally constrained macrocyclic platform. With use of surface plasmon
      resonance techniques, single-digit nanomolar affinities were exhibited by
      phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and
      4g, K(D) = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic
      phosphoryl mimetics provided affinities of K(D) = 16-67 nM. Neutral phosphoryl
      mimicking groups did not show appreciable binding.

PMID- 15943470
TI  - Anti-HIV activity of (-)-(2R,4R)-1- (2-hydroxymethyl-1,3-dioxolan-4-yl)-thymine
      against drug-resistant HIV-1 mutants and studies of its molecular mechanism.
AB  - (-)-(2R,4R)-1-(2-Hydroxymethyl-1,3-dioxolan-4-yl)thymine (DOT) is the first
      thymidine kinase-activated nucleoside that is significantly active against all of
      the clinically significant NRTI-resistant HIV-1 mutants, including AZT
      (D67N/K70R/T215Y/K219Q), Tenofovir (K65R), and Lamivudine (M184V). To understand
      the molecular mechanism of drug resistance and the antiviral activity of DOT
      against drug-resistant RTs, molecular modeling studies of DOT-TP complexed with
      the wild-type (WT) and mutated RT were conducted. The key reason for this
      interesting antiviral activity profile is the presence of a dioxolane ring.

PMID- 15943471
TI  - ERbeta ligands. 3. Exploiting two binding orientations of the 2-phenylnaphthalene
      scaffold to achieve ERbeta selectivity.
AB  - The 2-phenylnaphthalene scaffold was explored as a simplified version of
      genistein in order to identify ER selective ligands. With the aid of docking
      studies, positions 1, 4, and 8 of the 2-phenylnaphthalene template were predicted
      to be the most potentially influential positions to enhance ER selectivity using
      two different binding orientations. Both orientations have the phenol moiety
      mimicking the A-ring of genistein. Several compounds predicted to adopt
      orientations similar to that of genistein when bound to ERbeta were observed to
      have slightly higher ER affinity and selectivity than genistein. The second
      orientation we exploited, which was different from that of genistein when bound
      to ERbeta, resulted in the discovery of several compounds that had superior ER
      selectivity and affinity versus genistein. X-ray structures of two ER selective
      compounds (i.e., 15 and 47) confirmed the alternate binding mode and suggested
      that substituents at positions 1 and 8 were responsible for inducing selectivity.
      One compound (i.e., 47, WAY-202196) was further examined and found to be
      effective in two models of inflammation, suggesting that targeting ER may be
      therapeutically useful in treating certain chronic inflammatory diseases.

PMID- 15943472
TI  - Structure-based characterization and optimization of novel hydrophobic binding
      interactions in a series of pyrrolidine influenza neuraminidase inhibitors.
AB  - The structure-activity relationship (SAR) of a novel hydrophobic binding
      interaction within a subsite of the influenza neuraminidase (NA) active site was
      characterized and optimized for a series of trisubstituted pyrrolidine inhibitors
      modified at the 4-position. Previously, potent inhibitors have targeted this
      subsite with hydrophilic substituents such as amines and guanidines. Inhibitor
      bound crystal structures revealed that hydrophobic substituents with sp(2)
      hybridization could achieve optimal interactions by virtue of a low-energy
      binding conformation and favorable pi-stacking interactions with the residue
      Glu119. From a lead methyl ester, investigation of five-membered heteroaromatic
      substituents at C-4 produced a 3-pyrazolyl analogue that improved activity by
      making a targeted hydrogen bond with Trp178. The SAR of substituted vinyl
      substituents at C-4 produced a Z-propenyl analogue with improved activity over
      the lead methyl ester. The C-1 ethyl ester prodrugs of the substituted C-4 vinyl
      analogues gave compounds with excellent oral bioavailability (F > 60%) when dosed
      in rat.

PMID- 15943473
TI  - Design, synthesis, and evaluation of orally active 4-(2,4-difluoro-5
      (methoxycarbamoyl)phenylamino)pyrrolo[2,1-f][1,2,4]triazines as dual vascular
      endothelial growth factor receptor-2 and fibroblast growth factor receptor-1
      inhibitors.
AB  - A series of substituted 4-(2,4-difluoro-5
      (methoxycarbamoyl)phenylamino)pyrrolo[2,1-f][1,2,4]triazines was identified as
      potent and selective inhibitors of the tyrosine kinase activity of the growth
      factor receptors VEGFR-2 (Flk-1, KDR) and FGFR-1. The enzyme kinetics associated
      with the VEGFR-2 inhibition of compound 50 (K(i) = 52 +/- 3 nM) confirmed that
      the pyrrolo[2,1-f][1,2,4]triazine analogues are competitive with ATP. Several
      analogues demonstrated low-nanomolar inhibition of VEGF- and FGF-dependent human
      umbilical vein endothelial cell (HUVEC) proliferation. Replacement of the C6
      ester substituent of the pyrrolo[2,1-f][1,2,4]triazine core with heterocyclic
      bioisosteres, such as substituted 1,3,5-oxadiazoles, afforded compounds with
      excellent oral bioavailability in mice (i.e., 50 F(po) = 79%). Significant
      antitumor efficacy was observed with compounds 44, 49, and 50 against established
      L2987 human lung carcinoma xenografts implanted in athymic mice. A full account
      of the synthesis, structure-activity relationships, pharmacology, and
      pharmacokinetic properties of analogues within the series is presented.

PMID- 15943474
TI  - New selective AT2 receptor ligands encompassing a gamma-turn mimetic replacing
      the amino acid residues 4-5 of angiotensin II act as agonists.
AB  - New benzodiazepine-based gamma-turn mimetics with one or two amino acid side
      chains were synthesized. The gamma-turn mimetics were incorporated into
      angiotensin II (Ang II) replacing the Val(3)-Tyr(4)-Ile(5) or Tyr(4)-Ile(5)
      peptide segments. All of the resulting pseudopeptides displayed high AT(2)/AT(1)
      receptor selectivity and exhibited AT(2) receptor affinity in the low nanomolar
      range. Molecular modeling was used to investigate whether the compounds binding
      to the AT(2) receptor could position important structural elements in common
      areas. A previously described benzodiazepine-based gamma-turn mimetic with high
      affinity for the AT(2) receptor was also included in the modeling. It was found
      that the molecules, although being structurally quite different, could adopt the
      same binding mode/interaction pattern in agreement with the model hypothesis. The
      pseudopeptides selected for agonist studies were shown to act as AT(2) receptor
      agonists being able to induce outgrowth of neurite cells, stimulate
      p42/p44(mapk), and suppress proliferation of PC12 cells.

PMID- 15943475
TI  - Replacement of Phe6, Phe7, and Phe11 of D-Trp8-somatostatin-14 with L
      pyrazinylalanine. Predicted and observed effects on binding affinities at hSST2
      and hSST4. An unexpected effect of the chirality of Trp8 on NMR spectra in
      methanol.
AB  - An alanine scan performed in the 1970s suggested that Phe(6) and Phe(11) are
      required for the binding of somatostatin (SRIF-14). Molecular modeling studies
      and replacement of Phe(6) and Phe(11) with a cystine bridge affording ligands
      with the retention of high biological activity, however, led to the alternate
      conclusion that Phe(6) and Phe(11) stabilize the bioactive conformation of SRIF
      14. Subsequent studies revealed that Phe(11) shields Phe(6) in a "herringbone"
      arrangement. More recently, a report from this laboratory demonstrated that
      Spartan 3-21G MO calculations can be invaluable in explaining SARs in medicinal
      chemistry. For example, the ability of benzene and indole rings to bind the
      Trp(8) binding pocket for SRIF-14 and the inability of pyrazine to do so was
      explained through differences in electrostatic potentials. To investigate the
      role of Phe(6) and Phe(11) more fully, we report here the synthesis of two
      analogues of D-Trp(8)-SRIF in which Phe(6) and Phe(11) were replaced by the
      pryazinylalanine congeners, respectively. The NMR spectra in D(2)O and the K(i)s
      fully support the proposition that Phe(11) stabilizes the bioactive conformation
      through pi-bonding or aromatic edge-to-face interaction and that
      pyrazinylalanine(6) can be shielded by Phe(11). The data also show unexpectedly
      that Phe(6), via the pi-bond, interacts with the receptor, consistent with the
      original interpretation of the alanine scan. Heretofore it had only been known
      that Lys(9) interacts with an aspartate anion of the receptor. These conclusions
      are supported by recent studies of Lewis et al. on the effects on K(i)s of Ala(6)
      SRIF-14-amide at the five receptor subtargets. We also found that
      pyrazinylalanine(7)-D-Trp(8)-SRIF-14 does not bind, suggesting a repulsive
      interaction with the receptor. Taken together, our results not only validate
      predictions based on Spartan 3-21G MO analysis but also provide valuable
      information about the nature of the receptor interaction at the molecular level.
      Finally, the chirality of Trp(8) was unexpectedly found to have a striking effect
      on NMR spectra in methanol, especially at lower temperatures.

PMID- 15943476
TI  - A naive bayes classifier for prediction of multidrug resistance reversal activity
      on the basis of atom typing.
AB  - Multidrug resistance (MDR), the ability of cancer cells to become simultaneously
      resistant to different drugs, remains an unsolved challenge in cancer
      chemotherapy. The use of MDR reversal (MDRR) agents is a promising approach to
      overcome this problem. For the design and development of such agents, it would be
      desirable to have a reliable model to estimate the MDRR activity of compounds.
      Presented here is a naive Bayes classifier to categorize MDRR agents into active
      and inactive classes, which uses a universal, generic molecular-descriptor
      system.(1) The naive Bayes classifier was built from a 424 compound training set,
      selected from 609 druglike compounds in the publicly available "Klopman set". The
      model correctly predicted MDRR activities for 82.2% of 185 compounds in a testing
      set. The cumulative probabilities were proven useful for prioritizing the
      compounds for testing. The impact of attribute dependences on the performance of
      the classifier was examined. As an unsupervised learner with no tuning
      parameters, a naive Bayes classifier is capable of providing an objective
      comparison of the effectiveness of different molecular descriptors. The relative
      performance of the classifiers constructed from either an atom-type-based
      molecular descriptor or the long-range functional-class fingerprint descriptors
      FCFP_6 or FCFP_2 was compared. Employing an atom typing descriptor with the naive
      Bayes classification, it enables the interpretability of the resulting model,
      which offers extra information for the rational design of MDRR agents.

PMID- 15943477
TI  - Validation and use of the MM-PBSA approach for drug discovery.
AB  - The MM-PBSA approach has become a popular method for calculating binding
      affinities of biomolecular complexes. Published application examples focus on
      small test sets and few proteins and, hence, are of limited relevance in
      assessing the general validity of this method. To further characterize MM-PBSA,
      we report on a more extensive study involving a large number of ligands and eight
      different proteins. Our results show that applying the MM-PBSA energy function to
      a single, relaxed complex structure is an adequate and sometimes more accurate
      approach than the standard free energy averaging over molecular dynamics
      snapshots. The use of MM-PBSA on a single structure is shown to be valuable (a)
      as a postdocking filter in further enriching virtual screening results, (b) as a
      helpful tool to prioritize de novo design solutions, and (c) for distinguishing
      between good and weak binders (DeltapIC(50) > or = 2-3), but rarely to reproduce
      smaller free energy differences.

PMID- 15943478
TI  - Analysis of structure-activity relationships for MT2 selective antagonists by
      melatonin MT1 and MT2 receptor models.
AB  - Three-dimensional homology models of human MT(1) and MT(2) melatonin receptors
      were built with the aim to investigate the structure-activity relationships
      (SARs) of MT(2) selective antagonists. A common interaction pattern was proposed
      for a series of structurally different MT(2) selective antagonists, which were
      positioned within the binding site by docking and simulated annealing. The
      proposed antagonist binding mode to the MT(2) receptor is characterized by the
      accommodation of the out-of-plane substituents in a hydrophobic pocket, which
      resulted as being fundamental for the explanation of the antagonist behavior and
      the MT(2) receptor selectivity. Moreover, to assess the ability of the MT(2)
      receptor model to reproduce the SARs of MT(2) antagonists, three new derivatives
      of the MT(2) selective antagonist N-[1-(4-chloro-benzyl)-4-methoxy-1H-indol-2
      ylmethyl]-propionamide (7) were synthesized and tested for their receptor
      affinity and intrinsic activity. These compounds were docked into the MT(2)
      receptor model and were submitted to molecular dynamics studies, providing
      results in qualitative agreement with the experimental data. These results
      confirm the importance of the out-of-plane group in receptor binding and
      selectivity and provide a partial validation of the proposed G protein-coupled
      receptor model.

PMID- 15943479
TI  - Novel nonsteroidal antiinflammatory drugs possessing a nitric oxide donor diazen
      1-ium-1,2-diolate moiety: design, synthesis, biological evaluation, and nitric
      oxide release studies.
AB  - A novel group of hybrid nitric oxide-releasing nonsteroidal antiinflammatory
      drugs ((*)NO-NSAIDs) possessing a 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate
      (11, 13, 15) or 1-(N,N-dimethylamino)diazen-1-ium-1,2-diolate (12, 14, 16) moiety
      attached via a one-carbon methylene spacer to the carboxylic acid group of the
      traditional NSAIDs aspirin, ibuprofen, and indomethacin were synthesized.
      Although none of these ester prodrugs (11-16) exhibited in vitro cyclooxygenase
      (COX) inhibitory activity against the COX-1 and COX-2 isozymes (IC(50) > 100
      microM), all of the compounds (11-16) significantly decreased carrageenan-induced
      rat paw edema. In this regard, the ester prodrugs 11-16 showed equipotent
      antiinflammatory activities in vivo to that of the parent drugs aspirin,
      ibuprofen, and indomethacin. All of the compounds released nitric oxide upon
      incubation with either phosphate buffer solution at pH 7.4 (14-16% range) or
      porcine liver esterase (16-19% range), but the percentage of (*)NO released was
      up to sixfold higher (93%) when these ester prodrugs were incubated with guinea
      pig serum. These incubation studies suggest that both (*)NO and the parent NSAID
      would be released upon in vivo cleavage by nonspecific serum esterases. The
      simultaneous release of aspirin and nitric oxide from the (*)NO-aspirin prodrugs
      constitutes a potentially beneficial property for the prophylactic prevention of
      thrombus formation and adverse cardiovascular events such as stroke and
      myocardial infarction. The data acquired in an in vivo ulcer index (UI) assay
      showed that for this group of ester prodrugs, particularly the (*)NO-aspirins
      (11, 12) and (*)NO-ibuprofens (13, 14), no lesions were observed (UI = 0) when
      compared to the parent drugs aspirin (UI = 57, 250 mg/kg po dose), ibuprofen (UI
      = 45, 250 mg/kg po dose), or indomethacin (UI = 34, 30 mg/kg po dose) at
      equivalent doses. Accordingly, these hybrid (*)NO-NSAID prodrugs possessing a
      diazen-1-ium-1,2-diolate moiety, represent a new approach for the rational design
      of antiinflammatory drugs with reduced gastric ulcerogenicity.

PMID- 15943480
TI  - Synthesis, biological evaluation, and three-dimensional quantitative structure
      activity relationship study of small-molecule positive modulators of
      adrenomedullin.
AB  - Adrenomedullin (AM) is a peptide hormone implicated in blood pressure regulation
      and in the pathophysiology of several diseases such as hypertension, cancer,
      diabetes, and renal disorders, becoming an interesting new target for the
      development of drugs. In a recent high-throughput screening study, a positive
      modulator with a bistriazole structure has been identified.(1) In this work, a
      new series of structurally related compounds has been synthesized by reaction of
      phenoxyacetic acid with the corresponding dihydrazide, followed by treatment of
      the formed bisoxadiazoles with benzylamine. The affinity toward AM of the lead
      compound, and a structurally related family obtained from the small-molecule NCI
      library together with the synthesized series, has been determined. A three
      dimensional quantitative structure-activity relationship (3D-QSAR) study and
      conformational and molecular dynamics simulations have shown that the presence of
      a free NH and a phenyl group is essential for the interaction of these compounds
      with AM.

PMID- 15943481
TI  - BRUTUS: optimization of a grid-based similarity function for rigid-body molecular
      superposition. 1. Alignment and virtual screening applications.
AB  - We have developed a fast grid-based algorithm, BRUTUS, for rigid-body molecular
      superposition and similarity searching. BRUTUS aligns molecules using field
      information derived from charge distributions and van der Waals shapes of the
      compounds. Molecules can have similar biological properties if their charge
      distributions and shapes are similar, even though they have different chemical
      structures; that is, BRUTUS can identify compounds possessing similar properties,
      regardless of their structures. In this paper, we present two applications of
      BRUTUS. First, BRUTUS was used to superimpose five sets of inhibitors. Second,
      two sets of known inhibitors were searched from a database, and the results were
      analyzed using self-organizing maps. We demonstrate that BRUTUS is successful in
      superimposing compounds using molecular fields and, importantly, is fast and
      accurate enough for virtual screening of chemical databases using a standard
      personal computer. This fast and efficient molecular-field-based algorithm is
      applicable for virtual screening of structurally diverse, active molecules.

PMID- 15943482
TI  - Antineoplastic agents. 445. Synthesis and evaluation of structural modifications
      of (Z)- and (E)-combretastatin A-41.
AB  - A series of cis- and trans-stilbenes related to combretastatin A-4 (1a), with a
      variety of substituents at the 3'-position of the aryl B-ring, were synthesized
      and evaluated for inhibitory activity employing six human cancer cell lines (NCI
      H460 lung carcinoma, BXPC-3 pancreas, SK-N-SH neuroblastoma, SW1736 thyroid, DU
      145 prostate, and FADU pharynx-squamous sarcoma) as well as the P-388 murine
      lymphocyte leukemia cell line. Several of the cis-stilbene derivatives were
      significantly inhibitory against all cell lines used, with potencies comparable
      to that of the parent 1a. All were potent inhibitors of tubulin polymerization.
      The corresponding trans-stilbenes had little or no activity as tubulin
      polymerization inhibitors and were relatively inactive against the seven cancer
      cell lines. In terms of inhibition of both cancer cell growth and tubulin
      polymerization, the dimethylamino and bromo cis-stilbenes were the most potent of
      the new derivatives, the latter having biological activity approaching that of
      1a. As part of the present study, the X-ray crystal structure of the 3'-O
      phosphate of combretastatin A-4 (1b) was successfully elucidated. Compound 1b has
      been termed the "combretastatin A-4 prodrug", and it is currently undergoing
      clinical trials for the treatment of human cancer patients.

PMID- 15943483
TI  - Potent, orally active corticotropin-releasing factor receptor-1 antagonists
      containing a tricyclic pyrrolopyridine or pyrazolopyridine core.
AB  - Two new classes of tricyclic-based corticotropin-releasing factor (CRF(1))
      receptor-1 antagonists were designed by constraining known 1H-pyrrolo[2,3
      b]pyridine and 1H-pyrazolo[3,4-b]pyridine ligands. Pyrrole- and pyrazole-based
      molecules 19g and 22a, respectively, were discovered that potently bind the
      recombinant CRF(1) receptor (K(i) = 3.5, 2.9 nM) and inhibit adrenocorticotropic
      hormone (ACTH) release from rat pituitary cell culture (IC(50) = 14, 6.8 nM).
      These compounds show good oral bioavailabity (F = 24%, 7.0%) and serum half-lives
      in rats (t(1/2) = 6.3, 12 h) and penetrate the rat brain ([brain]/[plasma] =
      0.27, 0.52) but tend toward large volumes of distribution (V(D) = 38, 44 L kg(
      1)) and rapid clearances (CL = 70, 43 mL min(-1) kg(-1)). When given orally, both
      the pyrazole and the pyrrole leads dose-dependently inhibit stress-induced ACTH
      release in vivo. ACTH reductions of 84-86% were observed for 30 mg kg(-1) doses.

PMID- 15943484
TI  - The PDBbind database: methodologies and updates.
AB  - We have developed the PDBbind database to provide a comprehensive collection of
      binding affinities for the protein-ligand complexes in the Protein Data Bank
      (PDB). This paper gives a full description of the latest version, i.e., version
      2003, which is an update to our recently reported work. Out of 23 790 entries in
      the PDB release No.107 (January 2004), 5897 entries were identified as protein
      ligand complexes that meet our definition. Experimentally determined binding
      affinities (K(d), K(i), and IC(50)) for 1622 of these were retrieved from the
      references associated with these complexes. A total of 900 complexes were
      selected to form a "refined set", which is of particular value as a standard data
      set for docking and scoring studies. All of the final data, including binding
      affinity data, reference citations, and processed structural files, have been
      incorporated into the PDBbind database accessible on-line at http://
      www.pdbbind.org/.

PMID- 15943485
TI  - Polyamine-vectored iron chelators: the role of charge.
AB  - The utility of polyamines as vectors for the intracellular transport of iron
      chelators is further described. Consistent with earlier results with polyamine
      analogues, these studies underscore the importance of charge in the design of
      polyamine-vectored chelators. Four polyamine conjugates are synthesized, two of
      terephthalic acid [N(1)-(4-carboxy)benzoylspermine (7) and its methyl ester (6)]
      and two of (S)-2-(2,4-dihydroxyphenyl)-4,5-dihydro-4-methyl-4-thiazolecarboxylic
      acid [(S)-4'-(HO)-DADFT] [(S)-4,5-dihydro-2-[2-hydroxy-4-(12-amino-5,9
      diazadodecyl-oxy)phenyl]-4-methyl-4-thiazolecarboxylic acid (10) and its ethyl
      ester (9)]. These four molecules were evaluated in murine leukemia L1210 cells
      for their impact on cell proliferation (48- and 96-h IC(50) values), their
      ability to compete with spermidine for the polyamine transport apparatus (K(i)),
      and their intracellular accumulation. The data revealed that when neutral
      molecules (cargo fragments) were fixed to the polyamine vector, the conjugates
      competed well with spermidine for transport and were accumulated intracellularly
      to millimolar levels. However, this was not the case when the cargo fragments
      were negatively charged. Metabolic studies of the polyamine-vectored (S)-4'-(HO)
      DADFTs in rodents indicated that not only did the expected deaminopropylation
      step occur, but also a surprisingly high level of oxidative deamination at the
      terminal primary nitrogens took place. Finally, the iron-clearing efficiency of
      the (S)-4'-(HO)-DADFT conjugates was determined in a bile-duct-cannulated rodent
      model. Attaching the ligand to a polyamine vector had a profound effect on
      increasing the iron-clearing efficiency of this chelator relative to its parent
      drug.

PMID- 15943486
TI  - Rapid computational identification of the targets of protein kinase inhibitors.
AB  - We describe a method for rapidly computing the relative affinities of an
      inhibitor for all individual members of a family of homologous receptors. The
      approach, implemented in a new program, SCR, models inhibitor-receptor
      interactions in full atomic detail with an empirical energy function and includes
      an explicit account of flexibility in homology-modeled receptors through sampling
      of libraries of side chain rotamers. SCR's general utility was demonstrated by
      application to seven different protein kinase inhibitors: for each inhibitor,
      relative binding affinities with panels of approximately 20 protein kinases were
      computed and compared with experimental data. For five of the inhibitors
      (SB203580, purvalanol B, imatinib, H89, and hymenialdisine), SCR provided
      excellent reproduction of the experimental trends and, importantly, was capable
      of identifying the targets of inhibitors even when they belonged to different
      kinase families. The method's performance in a predictive setting was
      demonstrated by performing separate training and testing applications, and its
      key assumptions were tested by comparison with a number of alternative approaches
      employing the ligand-docking program AutoDock (Morris et al. J. Comput. Chem.
      1998, 19, 1639-1662). These comparison tests included using AutoDock in
      nondocking and docking modes and performing energy minimizations of inhibitor
      kinase complexes with the molecular mechanics code GROMACS (Berendsen et al.
      Comput. Phys. Commun. 1995, 91, 43-56). It was found that a surprisingly
      important aspect of SCR's approach is its assumption that the inhibitor be
      modeled in the same orientation for each kinase: although this assumption is in
      some respects unrealistic, calculations that used apparently more realistic
      approaches produced clearly inferior results. Finally, as a large-scale
      application of the method, SB203580, purvalanol B, and imatinib were screened
      against an almost full complement of 493 human protein kinases using SCR in order
      to identify potential new targets; the predicted targets of SB203580 were
      compared with those identified in recent proteomics-based experiments. These
      kinome-wide screens, performed within a day on a small cluster of PCs, indicate
      that explicit computation of inhibitor-receptor binding affinities has the
      potential to promote rapid discovery of new therapeutic targets for existing
      inhibitors.

PMID- 15943487
TI  - Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H
      naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of
      the dopamine D2 high-affinity state with positron emission tomography.
AB  - In vivo imaging of dopamine D2 receptors with agonist (as opposed to the more
      commonly employed antagonist) radiotracers could provide important information on
      the high-affinity (functional) state of the D2 receptor in illnesses such as
      schizophrenia, movement disorders, and addictions. We report here the
      radiosynthesis and evaluation of the potent D2 agonist (+)-4-propyl
      3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol, (+)-3, labeled with
      carbon-11, as a potential radiotracer for imaging the high-affinity state of
      dopamine D2 receptors with positron emission tomography (PET). [(11)C]-(+)-3 was
      reliably synthesized in the quantities and at the specific activities and
      radiochemical purities required for human PET studies. Ex vivo biodistribution
      studies in rat brain demonstrated that [(11)C]-(+)-3 crossed the blood-brain
      barrier readily and had an appropriate regional brain distribution for a
      radiotracer that maps dopamine D2 receptors. The binding of [(11)C]-(+)-3 was
      saturable and demonstrated an excellent signal-to-noise ratio as measured by its
      striatum-to-cerebellum ratio of 5.6, 60 min postinjection. The binding was highly
      stereospecific, and blocking and displacement studies were consistent with
      selective and specific binding to the dopamine D2 receptors. Further, [(11)C]-(+)
      3 showed marked and appropriate sensitivity to both increases and decreases in
      the levels of endogenous dopamine. Brain radioactive metabolite and
      physicochemical measurements are in full accord with the desired properties of a
      neuroreceptor imaging agent for PET. All of the above, coupled with the
      documented full D2 agonistic properties of (+)-3, strongly indicate that [(11)C]
      (+)-3 is a leading candidate radiotracer for the imaging of the dopamine D2 high
      affinity state using PET in human subjects.

PMID- 15943488
TI  - In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes.
AB  - The antitumor activity of the organometallic ruthenium(II)-arene complexes,
      RuCl(2)(eta(6)-arene)(PTA), (arene = p-cymene, toluene, benzene, benzo-15-crown
      5, 1-ethylbenzene-2,3-dimethylimidazolium tetrafluoroborate, ethyl benzoate,
      hexamethylbenzene; PTA = 1,3,5-triaza-7-phosphaadamantane), abbreviated RAPTA,
      has been evaluated. In vitro biological experiments demonstrate that these
      compounds are active toward the TS/A mouse adenocarcinoma cancer cell line
      whereas cytotoxicity on the HBL-100 human mammary (nontumor) cell line was not
      observed at concentrations up to 0.3 mM, which indicates selectivity of these
      ruthenium(II)-arene complexes to cancer cells. Analogues of the RAPTA compounds,
      in which the PTA ligand is methylated, have also been prepared, and these prove
      to be cytotoxic toward both cell lines. RAPTA-C and the benzene analogue RAPTA-B
      were selected for in vivo experiments to evaluate their anticancer and
      antimetastatic activity. The results show that these complexes can reduce the
      growth of lung metastases in CBA mice bearing the MCa mammary carcinoma in the
      absence of a corresponding action at the site of primary tumor growth.
      Pharmacokinetic studies of RAPTA-C indicate that ruthenium is rapidly lost from
      the organs and the bloodstream.

PMID- 15943489
TI  - Anesthetic potency of two novel synthetic polyhydric alkanols longer than the n
      alkanol cutoff: evidence for a bilayer-mediated mechanism of anesthesia?
AB  - The polyhydroxyalkanes 1,6,11,16-hexadecanetetraol (1) and 2,7,12,17
      octadecanetetraol (2) were synthesized utilizing the thiophene ring as a scaffold
      to affix the hydroxyalkyl chains by lithiation of the acidic alpha-hydrogens and
      subsequent desulfurization. Both compounds exhibited significant anesthetic
      potency, individually and in additivity studies with hexanol, using immobility in
      tadpoles as the phenotypic endpoint. These results, which contradict a protein
      binding mechanism in which cutoff results from steric hindrance, are consistent
      with recent predictions of a membrane-mediated mechanism involving the lateral
      pressure profile.

PMID- 15943490
TI  - Cyclic ADP-ribose analogues containing the methylenebisphosphonate linkage:
      effect of pyrophosphate modifications on Ca2+ release activity.
AB  - Analogues of cyclic ADP-ribose (cADPR) incorporating a methylenebisphosphonate
      linkage in the place of the pyrophosphate have been synthesized from nicotinamide
      adenine dinucleotide analogues enzymatically using Aplysia californica ADP
      ribosyl cyclase. Methylenebisphosphonate cyclic ADP-ribose (cADPR[CH(2)]) and
      methylenebisphosphonate cyclic 3-deaza-ADP-ribose (3-deaza-cADPR[CH(2)]) showed
      full agonist activity for release of Ca(2+) ions from sea urchin egg homogenates.
      The EC(50) for cADPR[CH(2)] was 856 nM and that for 3-deaza-cADPR[CH(2)] was 300
      nM, about 15- and 5-fold less potent than cADPR, respectively.

PMID- 15943491
TI  - Managing adverse events associated with botulinum toxin type A: a focus on
      cosmetic procedures.
AB  - Botulinum toxin A (BTXA) has become a widely used drug in cosmetic dermatology,
      not only to treat focal hyperhidrosis but also hyperkinetic facial lines,
      platysma bands, decollete bands, and other skin features. The spectrum of
      possible adverse effects of BTXA is broad but fortunately those that have been
      observed with cosmetic use of this product are generally mild and transient. The
      major tools for preventing adverse effects from BTXA are knowledge and skill. Use
      of correct injection techniques is mandatory since most unwanted effects are
      caused by incorrect technique. Knowledge of the target structures, e.g. the
      facial and extrafacial muscles, allows physicians to select the optimal dose,
      time and technique. The most common adverse effects are pain and hematoma. In the
      periocular region, lid and brow ptosis are important adverse effects. Adverse
      effects such as pain, hematoma, ecchymosis, and bruising may also occur in the
      upper and lower face and at extrafacial sites. Other possible adverse effects
      seen in other indications that the user of BTXA in cosmetic dermatology should be
      wary of include induction headaches and possible interaction with concomitant
      medications. Induction of neutralizing antibodies due to cosmetic BTXA treatment
      has not been observed. This article also outlines recommendations regarding use
      of BTXA. Of these, the most important for avoiding most unwanted adverse effects
      are the proper techniques of dilution, storage, and injection, as well as the
      careful exclusion of patients with any contraindications. Pain, hematoma,
      ecchymosis, and bruising can be prevented by cooling the skin before and after
      BTXA injection. Upper lid ptosis may be partly corrected using apraclonidine or
      phenylephrine eyedrops. If simple rules relating to the indications for and
      application of BTXA are followed, this is a safe and effective drug in cosmetic
      dermatology.

PMID- 15943492
TI  - Lentigo maligna : prognosis and treatment options.
AB  - Lentigo maligna is a premalignant melanocytic neoplasm occurring on the sun
      exposed skin of the middle-aged and elderly. It is believed to represent the in
      situ phase of lentigo maligna melanoma and, as such, cure is usually the aim of
      treatment. However, factors such as site and size of lesion and patient co
      morbidities may influence the treatment modality undertaken. Surgical excision is
      the treatment of choice to obtain clinical and histologic clearance, but many
      other modalities have been used with variable success. Mohs micrographic surgery
      is associated with the lowest recurrence rate at 4-5%, but conventional surgery,
      cryotherapy and radiotherapy also yield good results, with recurrence rates in
      the order of 7-10%. Other treatments have been tried but currently there are not
      enough data to support their routine use. In order to make the best decision
      regarding appropriate management of lentigo maligna, the dermatologist or surgeon
      must be aware of all the options available and the evidence supporting their use.

PMID- 15943493
TI  - Dermatologic signs in patients with eating disorders.
AB  - Eating disorders are significant causes of morbidity and mortality in adolescent
      females and young women. They are associated with severe medical and
      psychological consequences, including death, osteoporosis, growth delay and
      developmental delay. Dermatologic symptoms are almost always detectable in
      patients with severe anorexia nervosa (AN) and bulimia nervosa (BN), and
      awareness of these may help in the early diagnosis of hidden AN or BN. Cutaneous
      manifestations are the expression of the medical consequences of starvation,
      vomiting, abuse of drugs (such as laxatives and diuretics), and of psychiatric
      morbidity. These manifestations include xerosis, lanugo-like body hair, telogen
      effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis,
      acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo,
      paronychia, generalized pruritus, acquired striae distensae, slower wound
      healing, prurigo pigmentosa, edema, linear erythema craquele, acral coldness,
      pellagra, scurvy, and acrodermatitis enteropathica. The most characteristic
      cutaneous sign of vomiting is Russell's sign (knuckle calluses). Symptoms arising
      from laxative or diuretic abuse include adverse reactions to drugs. Symptoms
      arising from psychiatric morbidity (artefacta) include the consequences of self
      induced trauma. The role of the dermatologist in the management of eating
      disorders is to make an early diagnosis of the 'hidden' signs of these disorders
      in patients who tend to minimize or deny their disorder, and to avoid over
      treatment of conditions which are overemphasized by patients' distorted
      perception of skin appearance. Even though skin signs of eating disorders improve
      with weight gain, the dermatologist will be asked to treat the dermatological
      conditions mentioned above. Xerosis improves with moisturizing ointments and
      humidification of the environment. Acne may be treated with topical benzoyl
      peroxide, antibacterials or azaleic acid; these agents may be administered as
      monotherapy or in combinations. Combination antibacterials, such as erythromycin
      with zinc, are also recommended because of the possibility of zinc deficiency in
      patients with eating disorders. The antiandrogen cyproterone acetate combined
      with 35 microg ethinyl estradiol may improve acne in women with AN and should be
      given for 2-4 months. Cheilitis, angular stomatitis, and nail fragility appear to
      respond to topical tocopherol (vitamin E). Russell's sign may decrease in size
      following applications of ointments that contain urea. Regular dental treatment
      is required to avoid tooth loss.

PMID- 15943494
TI  - Non-acne dermatologic indications for systemic isotretinoin.
AB  - Systemic isotretinoin has been used to treat severe acne vulgaris for 20 years.
      However, isotretinoin also represents a potentially useful choice of drugs in
      many dermatologic diseases other than acne vulgaris. Diseases such as psoriasis,
      pityriasis rubra pilaris, condylomata acuminata, skin cancers, rosacea,
      hidradenitis suppurativa, granuloma annulare, lupus erythematosus and lichen
      planus have been shown to respond to the immunomodulatory, anti-inflammatory and
      antitumor activities of the drug. Isotretinoin also helps prevent skin cancers
      such as basal cell carcinoma or squamous cell carcinoma. A combination of
      systemic isotretinoin and interferon-alpha-2a may provide a more potent effect
      than isotretinoin alone in the prevention and treatment of skin cancers.Systemic
      isotretinoin may be considered as an alternative drug in some dermatologic
      diseases unresponsive to conventional treatment modalities. However, randomized
      clinical trials aimed at determining the role of systemic isotretinoin therapy in
      dermatologic diseases other than acne vulgaris are required.

PMID- 15943495
TI  - Mechanisms and clinical applications of the vacuum-assisted closure (VAC) Device:
      a review.
AB  - The use of sub-atmospheric pressure dressings, available commercially as the
      vacuum-assisted closure (VAC) device, has been shown to be an effective way to
      accelerate healing of various wounds. The optimal sub-atmospheric pressure for
      wound healing appears to be approximately 125 mm Hg utilizing an alternating
      pressure cycle of 5 minutes of suction followed by 2 minutes off suction. Animal
      studies have demonstrated that this technique optimizes blood flow, decreases
      local tissue edema, and removes excessive fluid from the wound bed. These
      physiologic changes facilitate the removal of bacteria from the wound.
      Additionally, the cyclical application of sub-atmospheric pressure alters the
      cytoskeleton of the cells in the wound bed, triggering a cascade of intracellular
      signals that increases the rate of cell division and subsequent formation of
      granulation tissue. The combination of these mechanisms makes the VAC device an
      extremely versatile tool in the armamentarium of wound healing. This is evident
      in the VAC device's wide range of clinical applications, including treatment of
      infected surgical wounds, traumatic wounds, pressure ulcers, wounds with exposed
      bone and hardware, diabetic foot ulcers, and venous stasis ulcers. VAC has also
      proven useful in reconstruction of wounds by allowing elective planning of the
      definitive reconstructive surgery without jeopardizing the wound or outcome.
      Furthermore, VAC has significantly increased the skin graft success rate when
      used as a bolster over the freshly skin-grafted wound. VAC is generally well
      tolerated and, with few contraindications or complications, is fast becoming a
      mainstay of current wound care.

PMID- 15943496
TI  - Imiquimod: in superficial basal cell carcinoma.
AB  - Imiquimod, available as a 5% cream, is a new topical treatment for adults with
      superficial basal cell carcinoma (BCC). The exact mechanism of action of
      imiquimod in superficial BCC is unknown. Imiquimod may act as a toll-like
      receptor-7 agonist, and is thought to exert its anti-tumor effect via
      modification of the immune response and stimulation of apoptosis in BCC cells.
      Topical imiquimod 5% cream effectively increased clinical and histologic
      clearance of single superficial BCC lesions compared with vehicle in patients
      enrolled in two large, well designed trials. Patients applied imiquimod five or
      seven times per week or vehicle for 6 weeks, and the composite clearance rates at
      12 weeks post-treatment for the corresponding treatment groups were 75%, 73%, and
      2%, respectively. In a trial investigating the long-term efficacy of imiquimod 5%
      cream following application five times per week for 6 weeks, a clinical clearance
      rate of 90% was reported at the initial 12-week post-treatment examination. The
      estimated rate of clinical clearance at the 1-year follow-up visit was 84%.
      Application site and local skin reactions were the most common adverse events
      reported by imiquimod recipients. The severity of erythema, erosion, and
      scabbing/crusting correlated positively with the composite and histologic
      response rates.

PMID- 15943500
TI  - Metamorphosis of vascular surgeons to endovascular specialists: must vascular
      surgery have an independent board and can we get there?

PMID- 15943501
TI  - Endografting increases total volume of AAA repairs but not at the expense of open
      surgery: experience in more than 1000 patients.
AB  - PURPOSE: To compare the volume of open graft replacements (OGR) for abdominal
      aortic aneurysm (AAA) versus endovascular aneurysm repairs (EVAR) over time and
      after modifying selection criteria. METHODS: A review was conducted of 1021
      consecutive patients who underwent AAA repair from 1989 through 2002: 496
      elective OGRs for infrarenal AAAs (STANDARD), 289 elective EVARs for infrarenal
      AAAs, 59 complex OGRs for suprarenal AAAs, and 177 emergent OGRs for ruptured
      AAAs. Patients from 1995 to 2002 were divided into 2 groups based on shifting
      treatment strategies; 454 patients were treated by STANDARD or EVAR at the
      surgeon's discretion between 1995 and 2000 (post EVAR). The second group
      comprised 161 patients treated in 2001-2002 after the introduction of "high-risk"
      screening criteria (age > or = 72 years, diabetes mellitus, renal dysfunction,
      impaired pulmonary function, or ASA class IV) that dictated EVAR whenever
      anatomically feasible. For comparison, 170 STANDARD repairs performed in the 6
      years prior to EVAR served as a control. RESULTS: While surgery for ruptured AAAs
      remained fairly stable over the 14-year period, the number of patients undergoing
      elective repair increased due to the implementation of EVAR. During the 6 years
      after its introduction, EVAR averaged 34.3 patients per year; after 2001, the
      annual frequency of EVAR increased to 41.5 (p > 0.05). In like fashion, the rate
      of STANDARD repairs increased to 41.3 patients per year versus 28.3 before EVAR
      (p = 0.032). ASA class IV patients increased by almost 9 fold in the recent
      period versus pre EVAR (p = 0.006). The overall mortality after elective
      infrarenal AAA repair decreased between the pre and post EVAR periods (6.5%
      versus 3.7%, p > 0.05) and fell still further to 1.2% in the most recent period
      (p = 0.021 versus pre EVAR). CONCLUSIONS: The implementation of an EVAR program
      increases the total volume of AAA repairs but does not reduce open surgical
      procedures. By allocating patients to EVAR or open repair based their risk
      factors, mortality was markedly reduced.

PMID- 15943502
TI  - Endovascular AAA repair with the aortomonoiliac EndoFit stent-graft: two years'
      experience.
AB  - PURPOSE: To evaluate the feasibility and efficacy of a specific aortomonoiliac
      endograft and the durability of the femorofemoral bypass for treatment of
      abdominal aortic aneurysm (AAA). METHODS: From 2002 to 2004, 39 high-risk (ASA
      III/IV) patients (36 men; median age 74 years, range 63-84) with AAA (n = 33) or
      AAA and common iliac artery aneurysm (n = 6) were treated with an EndoFit
      aortomonoiliac endograft and femorofemoral crossover bypass. The contralateral
      iliac axis was obstructed with an endoluminal occluder. Patients were followed
      with contrast-enhanced computed tomography at 1, 6, 12, and 24 months. RESULTS:
      EndoFit AMI stent-grafts were implanted successfully in all patients.
      Perioperative mortality was zero. Endoleak occurred in 3 (7.7%) cases. A proximal
      type I endoleak was identified at 1 month and was treated with a proximal cuff.
      Two type II endoleaks are under surveillance because the aneurysm sac shows no
      enlargement. Thrombosis of the femorofemoral graft occurred in 1 case during the
      immediate postoperative period due to insufficient inflow from a residual
      stenosis of the endograft (primary patency 97.5%). The deficit was treated
      successfully (secondary patency 100%). Two (5.1%) tunnel hematomas were treated
      conventionally. Median follow-up was 14 months (range 6-30). All patients are
      alive. None of the aneurysms has ruptured or been converted to an open procedure.
      Graft migration, serious infection, paraplegia, distal embolization, or any other
      serious complication has not been observed. CONCLUSIONS: In high surgical risk
      patients with complex iliac anatomy, aortomonoiliac endograft with femorofemoral
      crossover bypass is feasible and efficacious. Moreover, the midterm patency of
      the extra-anatomic bypass appears quite satisfactory.

PMID- 15943503
TI  - Influence of diabetes mellitus on the endovascular treatment of abdominal aortic
      aneurysms.
AB  - PURPOSE: To investigate the influence of diabetes mellitus on outcome after
      endovascular abdominal aortic aneurysm (AAA) repair. METHODS: Of 6017 patients
      enrolled in the EUROSTAR registry after undergoing endovascular AAA repair
      between May 1994 and December 2003, 731 (12%) had diabetes mellitus (690 men;
      mean age 72 years, range 37-100). Patient demographics, risk factors, aneurysm
      morphology, operative and procedural details, complications, major events, and
      regular follow-up information were compared. The relationships of complications
      and events to diabetes mellitus, which were tested with multivariate logistic
      regression analysis and Cox proportional hazards modeling, are expressed as odds
      ratios (OR) and hazard rates (HR) with 95% confidence intervals (CI). Survival
      was compared with life-table analysis. RESULTS: A significantly higher risk of
      device-related complications was observed in diabetic patients (8% versus 6%, p <
      0.049; OR 1.35, 95% CI 1.00 to 1.82). The greatest difference in the groups was
      in mortality, which was significantly higher in the diabetic population (13%)
      compared to the nondiabetic patients (10%, p < 0.039; OR 1.27, 95% CI 1.01 to
      1.59). Deaths, which occurred at a higher frequency within the 30-day
      perioperative period in diabetic patients, were primary due to cardiac
      complications. Insulin-controlled type 2 diabetic patients had significantly
      lower rates of early and late endoleaks and secondary interventions than diet
      controlled type 2 diabetics (p = 0.002, p = 0.0001, and p = 0.0008, respectively)
      and nondiabetic patients (p = 0.002, p = 0.0005, and p = 0.0025, respectively).
      The cumulative survival after 48 months did not differ significantly: 74% in
      diabetics and 79% in the population without diabetes. CONCLUSIONS: Patients with
      diabetes mellitus had a significantly higher early mortality rate after EVAR, but
      their long-term survival was similar to nondiabetic patients.

PMID- 15943504
TI  - Color duplex ultrasonography is insensitive for the detection of endoleak after
      aortic endografting: a systematic review.
AB  - PURPOSE: To synthesize the available evidence regarding the diagnostic accuracy
      of color duplex ultrasonography (CDU) versus the accepted gold-standard of
      contrast-enhanced computed tomography (CT) for the detection and classification
      of endoleaks after aortic endografting. METHODS: A systematic search of the
      literature was conducted using electronic bibliographical databases and other
      means to gather articles published between 1991 and 2004. Articles were
      scrutinized against inclusion/exclusion criteria that broadly followed the QUADAS
      quality assessment guidelines. The results of diagnostic CDU were expressed for
      each study as a 2x2 contingency table, and summary statistics
      (sensitivity/specificity with 95% confidence intervals [CI]) were calculated.
      Pooled and random effects meta-analyses were performed. RESULTS: Eight published
      studies and 2 unpublished studies from Charing Cross and St. George's Hospitals
      (711 patients, 1355 paired scans performed > or = 1 month after endografting)
      were eligible for inclusion. From meta-analyses, the pooled sensitivity of CDU
      (versus CT as the gold standard) was 69% (95% CI 52% to 87%) and the specificity
      of CDU was 91% (95% CI 87% to 95%). These parameters did not appear to vary over
      time when a smaller dataset of 117 patients with 239 paired scans was used to
      compare CT and CDU specifically at 3, 12, and 24 months after endografting.
      Endoleak classification data, which was derived from only 5 small studies,
      indicated that CDU appeared to have better diagnostic accuracy in detecting type
      I or type III endoleaks compared with type II endoleaks; however, the data were
      insufficient for statistical analysis. CONCLUSIONS: CDU currently does not have
      sufficient diagnostic accuracy for the detection of all endoleaks in routine
      clinical practice. The diagnostic accuracy of CDU may improve if type II
      endoleaks are ignored.

PMID- 15943505
TI  - Extension of dissection in stent-graft treatment of type B aortic dissection:
      lessons learned from endovascular experience.
AB  - Endovascular treatment is becoming the most important treatment modality in the
      complex management of type B dissection, providing benefits to both acute and
      chronic patients. Growing technical experience and improving stent-graft devices
      have resulted in better patient outcome and expanded clinical indications.
      Nevertheless, similar to any treatment option, this less invasive method has its
      inherent risks. Several cases of iatrogenic dissection have been reported in the
      literature, underlying the need for guidelines to minimize this risk and improve
      procedural safety. Extension of the dissection after endovascular repair of type
      B dissection does not appear to be device-specific, but related primarily to
      aortic wall alterations or adverse anatomy that arise most frequently in
      hypertensive patients or those with challenging aortic configuration. An accurate
      examination of the aortic wall and dissection anatomy and careful intraprocedural
      device manipulation and balloon molding may help avoid this potentially life
      threatening complication.

PMID- 15943506
TI  - Incidence of renal infarctions after transrenal stent placement in an animal
      model.
AB  - PURPOSE: To evaluate the incidence and appearance of renal infarctions after
      transrenal stent placement in an animal model. METHODS: An aortic stent was
      placed via a femoral approach in 20 female Merino sheep. Ten animals had
      intentional coverage of one renal ostium with the bare struts, 1 sheep had both
      renal artery ostia covered, and the other 9 sheep had no stent impingement on the
      renal orifices. Animals were sacrificed after 3 to 12 months (mean 6) for gross
      pathological and histological evaluation. Infarction locations and patterns were
      evaluated and correlated to stent placement. RESULTS: Of the 40 renal arteries,
      coverage was proven at autopsy in 12 cases; the remaining 28 arteries were free
      of any stent overlay. Overall, 14 (35%) renal infarctions were detected; 7 were
      found in the 12 arteries with a transrenal stent (58.3% incidence in covered
      renal arteries). By comparison, the other 7 infarctions were found in the 28
      unaffected arteries (25% incidence in noncovered renal arteries; p = 0.04). All
      infarctions appeared to be well-defined punctate lesions. CONCLUSIONS: A
      transrenal stent position in the abdominal aorta is related to increased renal
      infarctions in an animal model.

PMID- 15943507
TI  - Characterization of a new double-injury restenosis model in the rat aorta.
AB  - PURPOSE: To characterize a new rat model of restenosis for evaluation of local or
      systemic drug strategies. METHODS: Arterial lesions were induced by placement of
      silicone cuffs around the aorta of Lewis rats. After 21 days, the cuffs were
      removed, and a subgroup of rat aortas was subjected to secondary balloon injury.
      Remodeling of wall compartments and cell kinetics were assessed morphometrically
      at 3, 7, 14, 21, and 28 days after the single and double-injury approaches.
      Immunohistochemistry was used to assess the distribution of macrophages, smooth
      muscle cells, and proliferating cells within the layers of the arterial wall in
      the experimental groups versus sham-operated and untreated controls. RESULTS:
      After cuff placement, the adventitia initially undergoes significant enlargement,
      while the media shows a reduction in relative thickness. Accumulation of cells
      within the adventitia at 3 and 7 days is followed by a marked decline in cell
      density at 14 days, with simultaneously increasing cell numbers in the intima. At
      this time, activated macrophages are detected in the adventitia, indicating
      chronic inflammation. Following cuff placement, mild intimal hyperplasia
      develops. In the double-injury model, extensive neointimal hyperplasia forms
      rapidly, with a peak at 14 days. CONCLUSIONS: This new double-injury model is
      technically easy, and multiple experiments can be accrued in short periods of
      time. It provides an additional platform to identify new targets and strategies
      for the prophylaxis of postangioplasty restenosis.

PMID- 15943508
TI  - Short-term rapamycin for inhibition of neointima formation after balloon-mediated
      aortic injury in rats: is there a window of opportunity for systemic prophylaxis
      of restenosis?
AB  - PURPOSE: To evaluate the efficacy of limited short-term systemic administration
      of rapamycin to prevent neointimal intimal hyperplasia (NIH) in a double-injury
      rat model of restenosis. METHODS: Aortic lesions were induced by perivascular
      placement of silicone cuffs around the aorta of 36 Lewis rats. After 3 weeks, the
      cuffs were removed, and the vessels were subjected to secondary balloon injury.
      Rapamycin (sirolimus) was intravenously administered for 5 days in dosages of 0.5
      or 2 mg/kg/d beginning at various time points relative to the balloon injury: (1)
      days -2 to +2, (2) days 1 to 5, or (3) days 7 to 11. For each treatment period, 6
      rats received the 5-day course of the lower or higher dose of rapamycin. Eight
      rats served as controls undergoing 2-stage injury without rapamycin treatment.
      Morphometry and immunohistochemistry were performed at 21 days after angioplasty.
      RESULTS: NIH and intimal alpha-actin expression were inhibited by both dosages
      when treatment started 2 days before or 1 day after angioplasty. Results were
      statistically significant for the lower dose when started 1 day after angioplasty
      (p < 0.01) and for the higher dose when initiated 2 days before the intervention
      (p < 0.05). Treatment commencing at 7 days did not reduce NIH in either dosage
      group. CONCLUSIONS: In a double-injury rat model, NIH can be inhibited by short
      term systemic rapamycin, but suppression of early cell migration and
      proliferation is pivotal. A limited peri-interventional antiproliferative therapy
      may be of value as an adjunct to control restenosis after balloon angioplasty
      and/or stenting.

PMID- 15943509
TI  - Commentary: rat restenosis models: means for thorough restenosis research.

PMID- 15943510
TI  - Determining in-stent stenosis of carotid arteries by duplex ultrasound criteria.
AB  - PURPOSE: To develop customized duplex ultrasound criteria for assessment of in
      stent restenosis in the carotid arteries. METHODS: A retrospective review was
      conducted of 605 patients who underwent carotid artery stenting (CAS) from July
      1996 to August 2004 at a single institution. Data on the stented carotid artery
      were accumulated from patients who had carotid angiography and duplex ultrasound
      (US) within 30 days of each other. Preliminary review found 118 pairs of
      ultrasound scans and angiograms in stented carotid arteries. Peak systolic
      velocity (PSV), end-diastolic velocity (EDV), and internal carotid artery to
      common carotid artery ratio (ICA/CCA) were examined. Angiographic stenosis was
      graded by NASCET criteria and compared to velocity parameters at clinically
      relevant levels of stenosis. The Student t test was used to compare similarly
      obtained data from 41 nonstented carotid arteries. RESULTS: PSV, ICA/CCA ratio,
      and EDV increased to a greater degree in stented arteries with stenosis. In 50%
      to 69% stenotic arteries, mean ICA/CCA ratio was 4.74+/-0.61 in stented versus
      3.68+/-0.24 in nonstented carotid arteries (p = 0.043). In arteries with > or =
      70% stenosis, there were increases in PSV (475+/-22 versus 337+/-26 cm/s, p =
      0.001), EDV (172+/-23 versus 122+/-8 cm/s, p = 0.043), and the ICA/CCA ratio
      (8.18+/-2.19 versus 5.11+/-0.66, p = 0.063) in stented versus nonstented
      arteries, respectively. To detect > or = 70% angiographic stenosis, PSV > or =
      350 cm/s had 100% sensitivity, 96% specificity, 55% positive predictive value
      (PPV), and 100% negative predictive value (NPV); an ICA/CCA ratio > or = 4.75 had
      100% sensitivity, 95% specificity, 50% PPV, and 100% NPV. To predict > 50%
      stenosis, combining PSV > or = 225 cm/s and ICA/PCA ratio > or = 2.5 increased
      sensitivity (95%), specificity (99%), PPV (95%), NPV (99%), and accuracy (98%).
      CONCLUSIONS: PSV and ICA/CCA increase with stenosis to a greater extent in
      stented carotid arteries, necessitating revision of existing US criteria to
      follow CAS patients. To determine > or = 70% in-stent stenosis, PSV > or = 350
      cm/s and ICA/CCA ratio > or = 4.75 are sensitive criteria. To determine > or =
      50% stenosis, combining PSV > or = 225 cm/s and ICA/PCA ratio > or = 2.5 is
      optimal.

PMID- 15943511
TI  - Endoluminal stent-graft stabilization for thoracic aortic dissection.
AB  - PURPOSE: To review our experience with thoracic endografting for type B aortic
      dissection using the TAG Endoprosthesis. METHODS: A retrospective analysis was
      performed of data collected prospectively from March 2000 to July 2004 under an
      investigational device exemption protocol for the TAG thoracic endograft. In this
      time period, 40 patients (29 women; mean age 67 years, range 39-91) were treated
      with this endograft for type B aortic dissection. RESULTS: Technical success was
      95%. There was 1 (2.5%) perioperative death, and 1 (3%) endoleak was treated with
      an additional graft on postoperative day 2. Fifteen (38%) patients experienced
      postoperative complications, mainly renal or pulmonary, and 1 (3%) patient
      developed postoperative paraplegia that did not resolve. The 1-year survival was
      85%. Follow-up computed tomography was available for 31 patients with an average
      15-month follow-up. There was no significant change in size of the thoracic aorta
      in 22 patients; 8 aneurysmal segments were significantly reduced in size and 1
      thoracic aortic aneurysm expanded. No thoracic aortic ruptures were seen in this
      series. CONCLUSIONS: These early results indicate type B thoracic aortic
      dissections can be treated with acceptable morbidity and mortality using
      endografts. Stent-graft repair of the thoracic aorta may decrease the incidence
      of thoracic aortic expansion and rupture.

PMID- 15943512
TI  - Acute thromboembolic events during carotid artery angioplasty and stenting:
      etiology and a technique of neurorescue.
AB  - PURPOSE: To review the protected carotid stenting experience at two major
      referral centers to evaluate the frequency of clinically significant
      intraprocedural thromboembolic events, use of neurorescue techniques, and
      ultimate clinical outcomes. METHODS: A retrospective review was conducted of 254
      cases of protected transfemoral carotid stenting performed at the Washington
      University-Barnes Hospital and The Fleni Institute of Buenos Aires in a 6-year
      period. Medical records of patients with periprocedural thromboembolic events
      were reviewed to determine the type of complication, method of treatment, and
      outcome. RESULTS: Among the 254 cases in which a carotid protection device was
      used, 2 (0.79%) episodes of witnessed, symptomatic thromboembolism occurred. Both
      patients suffered thromboembolic occlusion of the M1 branch of the middle
      cerebral artery (MCA) immediately following crossing of the internal carotid
      lesion with the protection device. Neurological symptoms consisted of agitation,
      aphasia, and hemiplegia in both patients. After rapid stent deployment across the
      carotid lesion, the MCA was cannulated and the occlusion treated with balloon
      angioplasty. This was followed by selective intra-arterial delivery of urokinase
      and intravenous abciximab. These maneuvers resulted in excellent restoration of
      blood flow in the MCA and its branches. With the exception of minor word-finding
      difficulties in one, both patients demonstrated full neurological recovery within
      the perioperative period. CONCLUSIONS: In our experience, intraprocedural
      thromboembolic events occur despite the use of cerebral protection devices, but
      are rare. Notably these complications appeared to occur at the time of lesion
      crossing by distal cerebral protection devices. These thromboembolic events can
      be successfully treated if the complication is rapidly identified and the
      physician is adequately prepared and proficient in neurorescue techniques.

PMID- 15943513
TI  - Endovascular delivery of vein segments with valves versus direct anastomosis.
AB  - PURPOSE: To demonstrate an experimental model designed to allow placement of a
      vein segment containing a valve into a femoral vein without the need for
      anastomoses or surgical incision on the target limbs. METHODS: Segments of
      jugular veins containing valves were harvested bilaterally from 7 female dogs
      weighing 30 to 40 kg. One of the vein segments was then interposed into one
      femoral vein, using a standard surgical end-to-end anastomosis. Another segment
      was loaded into a self-expanding nitinol stent, everted, and secured outside of
      the stent. This vein-coated stent was then deployed from the jugular approach
      into the opposite common femoral vein. The endpoint of the study was thrombosis
      of one of the veins segments or patency at 120 days. The function of the valves
      was tested prior to completion of the study by instilling dye under incremental
      pressures and recording the pressure necessary to cause reflux. Light microscopy
      and electron microscopy were utilized to evaluate structure of the valves at
      study endpoint. RESULTS: Both grafts in one dog occluded during the second week
      after surgery. Anastomotic and vein-stented sites remained patent in the
      remaining 6 animals for 120 days. Retrograde phlebography demonstrated valve
      competency bilaterally in all cases. The reflux pressures on the stented side
      averaged 70 mmHg while the transplanted vein segment averaged 55 mmHg. Light
      microscopy and electron microscopy showed intact vein valve structure in all
      segments at the completion of the study. CONCLUSIONS: This experimental work
      demonstrates that endovascular delivery of a native canine vein containing a
      competent valve is feasible and effective.

PMID- 15943514
TI  - Drug-eluting biodegradable poly-D/L-lactic acid vascular stents: an experimental
      pilot study.
AB  - PURPOSE: To evaluate in vivo a new drug-eluting biodegradable vascular stent with
      respect to biocompatibility, neointimal hyperplasia formation, and reliability.
      METHODS: Self-expanding biodegradable poly-96L/4D-lactic acid (PLA) stents with 2
      drugs (PLA + dexamethasone [DEX] and PLA + simvastatin [SIM]) and 2 different
      coatings (PLA + P(D,L)LA and PLA + polycaprolactone [PCL]) were compared with a
      self-expanding stainless steel Wallstent. The stents were implanted in both
      common iliac arteries of 8 pigs. Prior to sacrifice at 1 month, angiography was
      performed to determine patency. Specimens were harvested for quantitative
      histomorphometry; vascular injury and inflammation scores were assigned to the
      stented iliac segments. RESULTS: All stented arteries were angiographically
      patent. The mean luminal diameter (3.05 mm) and area (30.36 mm2) of DEX-eluting
      PLA stents were decreased compared to other stents (PLA + P(D,L)LA: 3.66 mm and
      43.92 mm2; PLA + SIM: 4.21 mm and 56.48 mm2; PLA + PCL: 4.19 mm and 54.64 mm2;
      Wallstent: 5.01 mm and 81.19 mm2). Wallstents and DEX-eluting PLA stents induced
      minimal intimal hyperplasia: PLA + DEX: 0.16 mm, PLA + P(D,L)LA: 0.35 mm, PLA +
      SIM: 0.33 mm, PLA + PCL: 0.29 mm, and Wallstent: 0.18 mm. The vascular injury
      scores demonstrated only mild vascular trauma for all stents. Only mild to
      moderate inflammatory reaction was noted around stent struts with a vascular
      inflammation score. CONCLUSIONS: Biodegradable polymer stents appear to be
      biocompatible and reliable, causing minimal neointimal hyperplasia. Furthermore,
      the new biodegradable poly-D/L-lactic acid stent can be used as a local drug
      delivery vehicle. The DEX-eluting PLA stent reduces neointimal hyperplasia. The
      findings show a need for further investigation to prove the efficacy and safety
      of this new biodegradable drug-eluting stent.

PMID- 15943515
TI  - Three-dimensional analysis of renal artery bending motion during respiration.
AB  - PURPOSE: To evaluate displacement and bending of the renal arteries during
      respiration. METHODS: Seven men (mean age 59+/-7 years, range 54-71) were imaged
      with contrast-enhanced magnetic resonance angiography (MRA). Two phases of the
      MRA were acquired during separate normal inspiration and expiration breath-holds.
      Displacement of the kidneys and renal ostia and changes in renal branch angle
      were measured in both coronal and axial views. Arterial curvature and distances
      between inspiration and expiration renal artery centerlines were computed at 1-mm
      intervals for the first 2 cm of each branch. RESULTS: Significant kidney
      displacement was observed in both the coronal and axial views, with maximum
      displacement on the right side; the right kidney at expiration was 13.2+/-7 mm
      superior and 6.3+/-3.4 mm posterior of its position during inspiration. By
      comparison, the renal ostia were relatively fixed, displacing 10-fold less than
      the kidneys. This displacement differential resulted in significant renal branch
      angle changes between inspiration and expiration, with the branches being more
      perpendicular at expiration. Right and left branch angles were significantly
      different from each other in the axial view, with the right artery taking off
      more anteriorly. The renal artery centerlines were displaced approximately 2.5 mm
      at a distance of 1 cm from the ostia, with little displacement change in the
      second centimeter. The right renal artery was more curved than the left, with
      more respiratory-induced curvature change near the ostia. CONCLUSIONS: Positional
      change of the kidneys during respiration induces both bending and change in
      angulation of the renal arteries. This bending can have a complex 3-dimensional
      shape near the ostia. In the setting of renal artery stenting, this motion may
      adversely affect the artery and/or the stent, possibly contributing to
      restenosis.

PMID- 15943516
TI  - Do age and comorbidity affect quality of life or PTA-induced quality-of-life
      improvements in patients with symptomatic pad?
AB  - PURPOSE: To elucidate whether age or comorbidity influences (1) quality of life
      (QoL) or (2) the gain in QoL due to percutaneous angioplasty procedures in
      symptomatic peripheral arterial disease (PAD) patients. METHODS: One hundred two
      consecutive patients (81 men; mean age 66.3+/-9.1 years, range 44-83) with
      symptomatic PAD (83.2% with intermittent claudication, 16.8% with chronic
      critical limb ischemia) were tested cross-sectionally for their self-reported QoL
      and degree of leg pain during walking or rest according to standardized scales. A
      subgroup of 48 patients with a comparable clinical profile was prospectively
      investigated before and shortly after angioplasty. Quantitative indices of
      comorbidity burden and hemodynamic parameters were also obtained. RESULTS: QoL
      impairment significantly increased with a greater comorbidity burden and greater
      degree of leg pain during exercise or at rest, but decreased with advancing age
      (R = 0.91, p < 0.0001, stepwise regression). The angioplasty-associated gain in
      QoL, however, was positively correlated with the initial degree of QoL impairment
      and the degree of improvement in intermittent claudication (R = 0.873, p <
      0.0001, multiple regression). By contrast, neither age nor comorbidity burden
      adversely affected angioplasty-induced QoL improvements. CONCLUSIONS: PAD
      patients with higher levels of leg pain or a greater comorbidity burden generally
      have more pronounced QoL impairment. They can gain considerable QoL benefits from
      percutaneous procedures, especially if they have greater QoL impairment
      initially, and experience substantial improvements in exertional leg pain after
      treatment. In general, neither age nor comorbidity should negatively influence
      the decision for percutaneous therapy in symptomatic PAD patients.

PMID- 15943517
TI  - "Over-the-wire" inversion saphenectomy: a simple, minimally invasive vein
      harvesting technique for arterial bypass.
AB  - PURPOSE: To examine the feasibility and clinical outcome of a novel, minimally
      invasive technique for harvesting the great saphenous vein (GSV) for use in
      peripheral arterial bypass surgery. METHODS: Between May 2001 through March 2003,
      27 patients (15 men; mean age 71+/-10 years) underwent extremity bypass
      procedures for limb salvage (88%) or disabling claudication (12%) using the
      inversion technique to harvest the GSV. The veins were turned "inside out" using
      a unique catheter and guidewire system. With the endothelial surface exposed,
      valve leaflets were excised, and adherent thrombus was washed away. Veins were
      inverted again to turn the endothelial surface back inside the lumen for use as a
      bypass conduit. RESULTS: Inversion vein harvesting and arterial bypass were
      completed in 24 (89%) of 27 patients; 2 patients were treated with synthetic
      grafts because of small GSVs. Another patient was found after vein harvesting to
      have inadequate arterial outflow despite a good quality conduit. The average vein
      length was 45+/-10 cm; a mean 4+/-1 incisions were made, including those for
      arterial exposure. Incisions made to divide vein tributaries averaged 2 cm in
      length. Duration of vein harvesting was 25 minutes (range 5-80). Wound
      complications were minor (2 hematomas, 2 cases of erythema, 2 seromas). Of 6
      grafts that occluded after 30 days, 5 involved small-diameter vein grafts (< 3.5
      mm). At a mean 12 months, primary and assisted primary graft patency rates were
      88% (14/16) and 94% (15/ 16), respectively, for grafts with minimum diameters >
      or = 4 mm versus 38% (3/8) primary patency for veins < 4 mm (n = 8, p < 0.001).
      The limb salvage rate was 92% (22/24). CONCLUSIONS: Over-the-wire inversion
      saphenectomy is a simple and reliable minimally invasive technique for arterial
      bypass. Incisions are small and cosmetically superior to those of the traditional
      long incision method. One-year follow-up suggests that grafts harvested by
      inversion technique have excellent durability when the minimum vein diameter is >
      or = 4 mm, as determined by preoperative vein mapping.

PMID- 15943518
TI  - Use of a mechanical thrombectomy device to recanalize a subacutely occluded
      aortohepatic bypass after orthotopic liver transplantation.
AB  - PURPOSE: To report the use of a rotational thrombectomy device for recanalization
      of a thrombosed hepatic artery bypass graft in an orthotopic liver transplant
      (OLT). CASE REPORT: Six months after a second OLT in a 52-year-old man, an iliac
      conduit used for an aortohepatic bypass became occluded, interrupting arterial
      supply to the liver transplant. The 8-F Straub Rotarex system was used to
      successfully remove clot from the bypass graft, avoiding embolization to the
      hepatic arteries. The recanalized conduit has remained patent for 1 year with the
      patient on an anticoagulation regimen. CONCLUSIONS: The Rotarex thrombectomy
      system may be considered an alternative to other percutaneous interventions for
      the treatment of occluded bypass conduits supplying a liver transplant.

PMID- 15943520
TI  - Endovascular treatment of aortoureteric fistula.
AB  - PURPOSE: To report successful endovascular treatment of massive hemorrhage from
      an aortoureteric fistula. CASE REPORT: An 82-year-old man who had undergone total
      cystectomy and bilateral ureterostomy for bladder cancer was transferred with
      massive hemorrhage from the ureterostomy. Angiography demonstrated an
      aortoureteric fistula between the terminal aorta and the left ureter. The patient
      had pancytopenia from unknown causes on admission, so a stent-graft made from a
      Gianturco Z-stent covered with Dacron graft was implanted; complete hemostasis
      was obtained immediately. He died of coexistent plasma cell leukemia 42 days
      after the operation; however, complete hemostasis had been maintained, and
      infection around the stent-graft was not recognized at autopsy. CONCLUSIONS:
      Stent-graft implantation can be a useful therapy for control of massive bleeding
      from an aortoureteric fistula.

PMID- 15943519
TI  - Multiple HIV-related aneurysms: open and endovascular treatment.
AB  - PURPOSE: To report successful endovascular repair of thoracic aortic aneurysms in
      2 patients with human immunodeficiency virus (HIV). CASE REPORTS: Thoracic and
      abdominal aortic aneurysms (AAA) were found in a 60-year-old woman 1 year after
      she was diagnosed with HIV. Because of pain and risk of rupture, the AAA was
      repaired with conventional open techniques in February 1997, while the thoracic
      aneurysm was excluded in a staged procedure using a homemade endograft delivered
      through a 10-mm conduit sewn to the aortic tube graft. Two months later, new
      aneurysms were found in the superficial femoral arteries bilaterally; both were
      excised and replaced with vein grafts. After 7 years, the patient is well and no
      longer takes antiretroviral medication. Surveillance imaging shows continued
      patency of the stent-graft without evidence of leak or migration. In a more
      contemporary case, a 46-year-old man was found to have 5 focal aneurysms in the
      aorta; the most proximal descending thoracic aneurysm increased 2 cm in 2 weeks.
      The two thoracic aneurysms were successfully excluded using 2 Excluder stent
      grafts. At 7 months, he was doing well, and the aneurysm had shrunk 11 mm.
      CONCLUSIONS: Endovascular and open treatment of HIV-related aneurysms is
      possible, with excellent long-term results. Patients with long-life expectancy
      should be treated according to the same guidelines as patients without HIV.

PMID- 15943521
TI  - Re: is flow reversal the best method of protection during carotid stenting?

PMID- 15943522
TI  - A tale of two visions: can a new view of personality help integrate psychology?
AB  - Personality psychology studies how psychological systems work together.
      Consequently, the field can act as a unifying resource for the broader discipline
      of psychology. Yet personality's current fieldwide organization promotes a
      fragmented view of the person, seen through such competing theories as the
      psychodynamic, trait, and humanistic. There exists an alternative--a systems
      framework for personality--that focuses on 4 topics: identifying personality,
      personality's parts, its organization, and its development. This new framework
      and its view of personality are described. The framework is applied to such
      issues as personality measurement, psychotherapy outcome research, and education.
      The new framework may better organize the field of personality and help with its
      mission of addressing how major psychological systems interrelate.

PMID- 15943523
TI  - The Cinderella of psychology: the neglect of motor control in the science of
      mental life and behavior.
AB  - One would expect psychology--the science of mental life and behavior--to place
      great emphasis on the means by which mental life is behaviorally expressed.
      Surprisingly, however, the study of how decisions are enacted--the focus of motor
      control research--has received little attention in psychology. This article
      documents the neglect and considers possible reasons for it. The hypotheses
      considered include three that are raised and then rejected: (a) no famous
      psychologists have studied motor control, (b) cognitive psychologists are mainly
      interested in uniquely human functions, and (c) motor control is simply too hard
      to study. Three other hypotheses are more viable: (d) cognitive psychologists
      have been more interested in epistemology than in action, (e) psychologists have
      disfavored motor control because overt responses were the only admissible measure
      in behaviorism, and (f) psychologists have felt that neuroscientists have the
      market cornered when it comes to motor control research. There are signs that
      motor control's Cinderella status is changing.

PMID- 15943524
TI  - Psychology and phenomenology: a clarification.
AB  - Controversies are rampant in contemporary psychology concerning the appropriate
      method for observing consciousness and the role inner experience should play in
      psychological theorizing. These conflicting orientations reflect, in part,
      methodological differences between natural science and human science
      interpretations of psychology. Humanistic psychology and philosophical
      phenomenology both employ a human science approach to psychology that seeks to
      explain behavior in terms of a person's subjective existence. Maslow's and
      Heidegger's formulations are both fulfillment theories in that they specify moral
      values that suggest how life ought to be lived. Natural science methodology
      rejects the possibility that moral imperatives can be validated, whereas human
      science methodology allows phenomenological convictions to justify
      recommendations about a fulfilled life and a good society. The social role of
      psychology is analyzed within the framework of phenomenological convictions and
      scientific truth.

PMID- 15943525
TI  - Examining the personal-professional distinction: ethics codes and the difficulty
      of drawing a boundary.
AB  - The Ethics Code of the American Psychological Association (APA) applies to the
      professional role behaviors of members and not to their personal behavior. This
      article discusses some of the difficulties inherent in drawing distinctions
      between the personal and the professional. Consideration is given to the
      importance of clarifying public statements. Four ethics codes other than the APA
      Ethics Code are examined for how they treat the personal-professional
      distinction. A number of questions are posed to assist in determining the tilt a
      behavior takes. A concluding recommendation suggests that APA Ethical Standards
      be applied only to professional role behaviors, whereas aspirational principles
      might be applied to personal behavior.

PMID- 15943532
TI  - Relapse prevention needs more emphasis on interpersonal factors.

PMID- 15943533
TI  - Emphasis on interpersonal factors in a dynamic model of relapse.

PMID- 15943534
TI  - Definitions and omissions of heroism.

PMID- 15943535
TI  - Comparing the heroism of women and men.

PMID- 15943536
TI  - Psychology needs realism, not instrumentalism.

PMID- 15943537
TI  - Ontological and epistemic claims of realism and instrumentalism.

PMID- 15943538
TI  - The scientific denial of the real and the dialectic of scientism and humanism.

PMID- 15943539
TI  - Scientific symbiosis represents the mutual benefit of iteratively adopting the
      perspective of realism and instrumentalism.

PMID- 15943540
TI  - Giving psychology away is expensive.

PMID- 15943541
TI  - Shaping reduced smoking in smokers without cessation plans.
AB  - Most smokers do not plan to quit in the next 6 months. The authors previously
      demonstrated that percentile schedules shape lower breath carbon monoxide (BCO)
      levels in smokers trying to quit (R. J. Lamb, A. R. Morral, K. C. Kirby, M. Y.
      Iguchi, & G. Galbicka, 2004). In that study, the authors set reinforcement
      criteria based on the 9 most recent samples. In this study, the authors examined
      whether a more responsive procedure using the 4 most recent samples is more
      effective in smokers not trying to quit. Following institution of the
      contingencies in both groups, BCO levels were substantially reduced, and
      readiness to quit and cessation self-efficacy increased. However, more
      individuals in the 4-sample window group achieved a BCO level below 4 ppm,
      indicating recent abstinence. These individuals did so more rapidly and for a
      greater number of visits.

PMID- 15943542
TI  - Using behavioral theories of choice to predict drinking outcomes following a
      brief intervention.
AB  - Behavioral theories of choice predict that substance use is partly a function of
      the relative value of drugs in relation to other available reinforcers. This
      study evaluated this hypothesis in the context of predicting drinking outcomes
      following an alcohol abuse intervention. Participants (N = 54, 69% female, 31%
      male) were college student heavy drinkers who completed a single-session
      motivational intervention. Students completed a baseline measure of substance
      related and substance-free activity participation and enjoyment. Only women
      showed a significant reduction in drinking at the 6-month follow-up, and the
      ratio of substance-related to substance-free reinforcement accounted for unique
      variance in their drinking outcomes. Women who at baseline derived a smaller
      proportion of their total reinforcement from substance use showed lower levels of
      follow-up drinking, even after the authors controlled for baseline drinking
      level. Male and female participants who reduced their drinking showed increased
      proportional reinforcement from substance-free activities.

PMID- 15943543
TI  - Effectiveness of payment for reduced carbon monoxide levels and noncontingent
      payments on smoking behaviors in cocaine-abusing outpatients wearing nicotine or
      placebo patches.
AB  - In a 2-week intervention to reduce cigarette smoking among outpatients in
      treatment for cocaine addiction, 20 subjects were randomly assigned to a
      contingent group, receiving monetary vouchers for breath samples with carbon
      monoxide (CO) levels of 8 ppm or less, or to a noncontingent group, receiving
      vouchers regardless of CO level. Subjects wore either nicotine or placebo patches
      in a randomized crossover design. Contingent subjects had significantly lower CO
      levels and met the 8 ppm target significantly more often than did noncontingent
      subjects; however, number of cigarettes reported smoked did not differ between
      groups. Use of nicotine patches resulted in CO levels significantly lower than
      did use of placebo patches, but levels still exceeded 8 ppm regardless of type of
      patch. Because contingent reward helped cocaine-dependent smokers achieve
      nonsmoking CO targets, behavioral antismoking interventions merit continued study
      in similar populations.

PMID- 15943544
TI  - Transdermal methylphenidate, behavioral, and combined treatment for children with
      ADHD.
AB  - Stimulant medication and behavioral treatments are evidence-based for children
      with attention-deficit/hyperactivity disorder, but the combination of the 2
      treatments has been understudied. In this investigation, methylphenidate (MPH)
      was crossed with 2 levels of behavior modification (BMOD) in a summer treatment
      program. Twenty-seven children with attention-deficit/hyperactivity disorder,
      aged 6-12, participated. Children received placebo and 3 doses of transdermal MPH
      (12.5 cm(2), 25.0 cm(2), and 37.5 cm(2)). BMOD was implemented on alternating
      weeks. Both treatments produced large and significant effects. Combined treatment
      was superior to either treatment alone. The effects of transdermal MPH were
      comparable to those found in this setting in previous studies with multiple
      stimulant medications and formulations. Consistent with other research, low doses
      of MPH--even lower than in previous studies--yielded enhanced effects in
      combination with behavior modification.

PMID- 15943545
TI  - One too many: predicting future alcohol consumption following heavy drinking.
AB  - Adult social drinkers used handheld computers to monitor alcohol intake as well
      as the precursors and consequences of drinking over a 2-week period. The within
      person relationship between mood and amount of alcohol consumed was examined, as
      well as the role of individual differences. When individuals made internal
      attributions for their greater than average consumption, they were in a more
      negative mood after drinking. Individuals who experienced a negative mood after
      drinking consumed more subsequently. This dysregulatory process may help explain
      the progression from social drinking to more problematic drinking; indeed, the
      relationship between mood and alcohol intake was stronger for heavier drinkers.
      Likewise, gender and trait temptation and restriction moderated this process. The
      results are consistent with the Limit Violation Effect model (R. L. Collins,
      1993) of mood and regulation of alcohol intake.

PMID- 15943546
TI  - Syllogistic reasoning performance in MDMA (Ecstasy) users.
AB  - Previous research has demonstrated working memory and executive deficits in
      recreational users of MDMA (3,4-methylenedioxymethamphetamine; Ecstasy). In turn,
      both of these constructs have been implicated in syllogistic reasoning
      performance. Twenty-two MDMA users (mean age = 21.36) and 26 MDMA nonuser
      controls (mean age = 21.31) were tested on syllogisms of varying difficulty and
      on measures of working memory and executive functioning. MDMA users were
      significantly impaired in aspects of syllogistic reasoning, and the effect
      remained significant after the authors controlled for the use of other drugs.
      However, the MDMA-related variance was reduced to below statistical significance
      following control for group differences in working memory span. The results are
      consistent with the possibility that MDMA-related deficits in aspects of
      executive functioning result in impaired reasoning performance among MDMA users.

PMID- 15943547
TI  - Influence of physical attractiveness and alcohol on men's perceptions of
      potential sexual partners and sexual behavior intentions.
AB  - The current research presents the results of 2 related experimental studies
      designed to evaluate the influence of physical attractiveness and a moderate dose
      of alcohol on men's perceptions of potential sexual partners and sexual behavior
      intentions. Analyses revealed significant effects of physical attractiveness on
      partner perceptions and sexual behavior intentions. Although no main effects of
      alcohol were observed, alcohol differentially moderated the relations between
      perceived risk and sexual behavior intentions by limb of absorption. Results
      suggest that greater attention should be focused on identifying the specific
      physical characteristics of a potential sexual partner--beyond attractiveness-
      that influence perceptions of risk and intentions to engage in safer sex
      behaviors and highlight the importance of assessing limb of absorption in
      evaluating the complex association between alcohol and risky sexual behavior.

PMID- 15943548
TI  - Comprehensive screening of the thiopurine methyltransferase polymorphisms by
      denaturing high-performance liquid chromatography.
AB  - The drug-metabolizing enzyme thiopurine S-methyltransferase (TPMT) catalyzes the
      S-methylation of thiopurines such as 6-mercaptopurine, 6-thioguanine, and
      azathiopurine, which are used as immunosuppressants and in the treatment of acute
      lymphoblastic leukemia and rheumatoid arthritis. TPMT enzymatic activity is a
      polymorphic trait, and poor metabolizers may develop life-threatening bone marrow
      failure. To avoid such adverse effects, the TPMT enzymatic activity in patients'
      red blood cells (RBCs) is routinely measured prior to thiopurine administration
      in a limited number of oncology clinics. In the present study, we took advantage
      of a highly sensitive and specific automated denaturing high-performance liquid
      chromatography (dHPLC) technique that not only detects known polymorphic alleles,
      but also identifies previously uncharacterized sequence variants. We developed a
      dHPLC-based protocol to analyze the entire coding region and validated the
      protocol to detect all 16 previously described variant alleles. We further
      analyzed the entire coding region of the TPMT gene in 288 control samples
      collected worldwide and identified two novel amino acid substitutions Arg163Cys
      (487C>T) and Arg226Gln (677G>A) within exons 7 and 10, respectively. The clinical
      application of this comprehensive screening system for examining the entire TPMT
      gene would help to identify patients at risk for bone marrow failure prior to 6
      mercaptopurine therapy.

PMID- 15943549
TI  - A typing system for the major histocompatibility complex class I chain related
      genes A and B using polymerase chain reaction with sequence-specific primers.
AB  - The Major Histocompatibility Complex (MHC) class I chain related (MIC) A and B
      genes are important additional loci within the MHC. We have developed a MICA and
      MICB typing system using the polymerase chain reaction with sequence-specific
      primers (PCR-SSP), which operates under the same conditions as our routine HLA-A,
      -B, and -C typing method. We designed 95 primers in 84 SSP mixtures for MICA and
      39 primers in 29 mixtures for MICB. This detected and differentiated all 55 MICA
      and 19 MICB alleles (except MICA*00701 from MICA*026, MICA*00201 from MICA*020,
      and three MICB alleles, which are intronic variations). A computer program
      confirmed the MICA amplification reactivity of each SSP mixture and evaluated the
      typing set for MICA allele combination ambiguities. Seventy-six "reference" DNA
      samples were used for validation: 50 from International Histocompatibility
      Workshop B lymphoblastoid cell lines (IHW BCLs) and 26 MICA-typed samples from
      two laboratories. The reference material identified 28 out of the 55 MICA alleles
      and 13 of the 19 MICB alleles, and directly validated 62 of the 84 MICA and 20 of
      the 29 MICB SSP mixtures. Our genotyping agreed with 283 out of the 286 (98.95%)
      MICA and MICB reference laboratories' allele assignments or the consensus
      assignments. Two of the discrepancies remain unresolved, whereas one was probably
      due to a reference laboratory's failure to differentiate alleles differing in
      exon 5 of the MICA gene. A comparison of the MICA and MICB allele assignments
      between laboratories identified a "disagreement rate" of 19.4% for MICA alleles
      and 13.1% for MICB alleles. Accordingly, we have compiled "consensus" MICA and
      MICB genotypes for the 50 IHW BCLs tested, which have been confirmed by our
      typing. We also typed 166 random blood donors. Their MICA and MICB carriage and
      allele frequencies and HLA-B, MICA, MICB linkage disequilibrium parameters and
      haplotype frequencies largely concurred with other published data on United
      Kingdom subjects, further supporting the validity of our typing system. This PCR
      SSP system is a simple, reliable and rapid technique for typing MICA and MICB
      alleles. It is easily updated as new alleles are identified but clearly requires
      a continuing validation review until all known MICA and MICB alleles have been
      identified.

PMID- 15943550
TI  - Specific triplex binding capacity of mixed base sequence duplex nucleic acids
      used for single-nucleotide polymorphism detection.
AB  - Specific base recognition and binding between native double-stranded DNA (dsDNA)
      and complementary single-stranded DNA (ssDNA) of mixed base sequence is
      presented. Third-strand binding, facilitated and stabilized by a DNA
      intercalator, YOYO-1, occurs within 5 min at room temperature. This triplex
      binding capability has been used to develop a homogeneous assay that accurately
      detects 1-, 2-, or 3-bp mutations or deletions in the dsDNA target. Every type of
      1-bp mismatch can be identified. The assay can reliably distinguish homozygous
      from heterozygous polymerase chain reaction (PCR)-amplified genomic dsDNA, thus
      providing a highly sensitive clinical diagnostic assay.

PMID- 15943551
TI  - The implication of de novo 21-hydroxylase mutation in clinical and prenatal
      molecular diagnoses.
AB  - We studied 37 unrelated families with a history of 21-hydroxylase deficiency
      (CYP21D) for eight common mutations and gene deletions in the 21-hydroxylase
      (CYP21) gene. We found de novo mutations in the CYP21 gene in two CYP21D
      patients. Analysis for eight common mutations in the 21-hydroxylase gene as well
      as large gene deletions was accomplished using polymerase chain reaction (PCR)
      followed by amplified created restriction site (ACRS) or restriction fragment
      length polymorphism (RFLP) and Southern blot followed by hybridization to a CYP21
      specific probe. Linkage analysis was performed using microsatellite markers
      flanking the CYP21 gene. Ten short tandem repeat (STR) markers were used to
      confirm parentage in the two de novo mutation cases. In two prenatal diagnosis
      cases, an intron 2-13A/C>G mutation was identified in the proband, but not in the
      fetus, although the proband and fetus had identical linkage markers.
      Subsequently, the mutation was confirmed to be absent in the parents' genome and
      misparentage was ruled out. Our findings are consistent with previous studies
      showing a de novo mutation frequency of approximately 1.0-1.5% in the CYP21 gene.
      This new mutation rate is high relative to the rate of approximately one in one
      million for other autosomal recessive disorders. Thus, the de novo mutation rate
      in the CYP21 gene is not negligible. It must be considered and discussed in
      prenatal diagnosis and genetic counseling for this relatively common inherited
      disorder.

PMID- 15943552
TI  - The Arg482His mutation in the beta-galactosidase gene is responsible for a high
      frequency of GM1 gangliosidosis carriers in a Cypriot village.
AB  - GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of beta
      galactosidase. It is mainly characterized by progressive neurodegeneration, and
      in its most severe infantile form, it leads to death before the age of 4. The
      GLB1 gene gives rise to two alternatively spliced mRNAs that encode the beta
      galactosidase and the elastin binding protein (EBP). The diagnosis of two
      patients with the infantile form of GM1 gangliosidosis and 11 carriers in a small
      mountainous village in Cyprus prompted us to carry out a study in order to
      establish the frequency of carriers in the village and identify the mutations
      involved. Carrier detection was initially based on the measurement of beta
      galactosidase activity in leucocytes. Among 85 random samples from the village,
      10 were classified as carriers. Sequencing of the GLB1 gene in a Cypriot patient
      identified the missense mutation c.1445G>A (p.Arg482His) in the homozygous state.
      Seven of the 10 carriers identified using the enzyme assay were found to carry
      the same mutation by NspI restriction enzyme analysis. The three individuals who
      were negative for the c.1445G>A had borderline enzyme results and were probably
      wrongly classified as carriers. The frequency of GM1 gangliosidosis carriers in
      this village is approximately 8% (1:12). Western blot analysis showed a marked
      decrease of the 64-kDa mature form of the enzyme protein and a similar reduction
      of the 67-kDa EBP. Our results indicate that the c.1445G>A mutation, which
      appears to be responsible for all GM1 gangliosidosis alleles in this Cypriot
      village, affects protein conformation.

PMID- 15943553
TI  - Genetic analysis carried out on blood-spots of phenylalanine hydroxylase
      deficient newborns detected by northeastern Italian neonatal screening.
AB  - The aim of this work was to perform genetic analysis on 18 different blood-spot
      samples collected from neonates detected as hyperphenylalaninemic by Northeastern
      Italian screening program. DNA was extracted from blood-spots. Exons/introns of
      PAH gene were amplified by polymerase chain reaction (PCR), and PCR products were
      purified and sequenced with both forward and reverse primers. The most frequent
      mutations were IVS12nt1g>a (16.7%) and R408W, P281L and L48S (all together
      11.1%). As expected, compound heterozygosity was the usual finding; homozygosity
      was found only in two patients with R158Q and IVS2nt5g>c mutations. The V230I
      mutation was reported for the first time in Italy. We found six previously
      described polymorphisms (V245V, IVS4nt47c>t, IVS2nt19t>c, IVS3nt-22c>t, IVS5nt
      54a>g, and E280>Q280). To our knowledge, four genotypes were not previously
      described: R158Q/V230I present in one patient with classical PKU; and L48S/R408Q,
      A403V/IVS2nt-13t>g, and G272X/V230I present in patients showing HPA phenotype.
      Most of the mutations were located in the exons 12 and 7 and in exon/intron 2
      (83.3% detection of total mutations in PKU or HPA patients of Northeastern
      Italy). From a practical viewpoint, the genetic analysis of blood-spots collected
      on Guthrie cards for neonatal screening for PKU could be a simple method to
      establish the genotype of neonates. Consequently, the genotype/phenotype
      correlation could lead to a more accurate diagnosis and prognosis for families.

PMID- 15943554
TI  - Deletions account for 17% of pathogenic germline alterations in MLH1 and MSH2 in
      hereditary nonpolyposis colorectal cancer (HNPCC) families.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is due to defects in DNA
      mismatch repair (MMR) genes MSH2, MLH1, MSH6, and to a lesser extent PMS2. Of 466
      suspected HNPCC families, we defined 54 index patients with either tumors of high
      microsatellite instability (MSI-H) and/or loss of expression for either MLH1,
      MSH2, and/or MSH6, but without a detectable pathogenic point mutation in these
      genes. This study cohort was augmented to 64 patients by 10 mutation-negative
      index patients from Amsterdam families where no tumors were available.
      Deletion/duplication screening using the multiplex ligation-dependent probe
      amplification (MLPA) revealed 12 deletions in MSH2 and two deletions in MLH1.
      These deletions constitute 17% of pathogenic germline alterations but elucidate
      the susceptibility to HNPCC in only 22% of the mutation-negative study cohort,
      pointing towards other mutation mechanisms for an inherited inactivation of MLH1
      or MSH2. We describe here four novel deletions. One novel and one known type of
      deletion were found for three and two unrelated families, respectively. MLPA
      analysis proved a reliable method for the detection of genomic deletions in MLH1
      and MSH2; however, sequence variations in the ligation-probe binding site can
      mimic single exon deletions.

PMID- 15943555
TI  - Germline mutations in the MYH gene in Swedish familial and sporadic colorectal
      cancer.
AB  - Biallelic germline mutations in the base excision repair gene MYH have been shown
      to predispose to a proportion of multiple colorectal adenomas and cancer. To
      evaluate the contribution of MYH mutations to non- FAP, non-HNPCC familial
      colorectal cancer, 84 unrelated Swedish individuals affected with colorectal
      cancer from such families were screened for germline mutations in the coding
      sequence of the gene. None of the cases was found to carry any pathogenic
      sequence change. We then determined the prevalence of the two most common
      pathogenic MYH mutations found in Caucasians, Y165C and G382D, in 450 Swedish
      sporadic colorectal cancer cases and 480 Swedish healthy controls. The frequency
      of both variants in Swedish cases and controls was similar to those previously
      reported. In addition, we found that previously unknown sequence variations at
      the position of amino acid 423 (R423Q, R423P, and R423R) appear to occur more
      frequently in cases than in controls (p = 0.02), a finding that warrants future
      studies.

PMID- 15943556
TI  - Gender differences in attitudes among those at risk for Huntington's disease.
AB  - This report presents and discusses selected findings regarding gender differences
      from an Australian-based study that investigated attitudes of individuals at risk
      for Huntington's disease (HD) towards genetic risk and predictive testing. Clear
      gender differences emerged regarding perceived coping capacity with regard to
      predictive testing, as well as disclosure of the genetic risk for HD to others.
      Female participants were more likely to disclose their genetic risk to others,
      including their medical practitioners, while male participants were three times
      more fearful of disclosing their genetic risk to others. These findings are of
      interest in light of gender differences that have consistently been reported
      regarding the uptake of predictive testing for HD, other genetic conditions, and
      health services more generally. While gender differences cannot provide a fully
      explanatory framework for differential uptake of predictive genetic testing, men
      and women may experience and respond differently to the genetic risk for HD and
      possibly other inherited disorders. The meanings of genetic risk to men and women
      warrants further exploration, given anticipated increases in genetic testing for
      more common conditions, especially if post-test interventions are possible. These
      issues are also relevant within the context of individuals' concerns about the
      potential for discrimination on the basis of genetic risk or genetic test
      information.

PMID- 15943557
TI  - Preconception cystic fibrosis carrier screening: costs and consequences.
AB  - The objective of the study was to determine net costs of four potential
      preconception cystic fibrosis (CF) carrier screening strategies, and to identify
      the most important cost-related parameters. An estimate was made of the costs of
      screening carried out during general practitioner (GP) consultations, and
      screening carried out during group educational sessions. Two test strategies were
      evaluated: single-entry two-step (SETS) and double- entry two-step (DETS).
      Several sensitivity analyses were performed. Under the baseline assumptions, SETS
      screening during GP consultations was the least expensive (net costs US dollar
      1,111,354 per year). The sensitivity analysis showed that the costs depend
      greatly on the estimated lifetime costs of care for a CF patient and the strategy
      used to inform the target population. Adaptations could be made to the screening
      program, resulting in economic savings while the primary goal of the screening-
      to enable participants to make an autonomous informed choice--is guaranteed.

PMID- 15943558
TI  - Does genetic counseling have any impact on management of breast cancer risk?
AB  - Despite there being an increasing literature on the impact of cancer genetic
      counseling on risk perception and mental health, there is a lack of data
      describing impact on risk management. Genetic counseling and testing for cancer
      predisposition genes aims to improve the future health of those at high risk
      through appropriate surveillance and screening. However, management of breast
      cancer risk in women with a family history of this disease is an area of
      controversy. Counseling services may recommend specific risk management options
      to women, who then rely on their local screening service to make provision. This
      study investigated the impact of genetic counseling on management of breast
      cancer risk in women attending Cancer Family Clinics. A total of 293 women
      attending four genetic clinics were enrolled. Rates of breast self-examination,
      clinical breast examination, mammography, biopsy, detected cancers, and other
      screenings were documented. Participants' perceived benefits and barriers to
      mammography were assessed along with cancer worry. Results show that rates of
      mammography, clinical breast examination, and breast self-examination were
      increased following clinic attendance (p < 0.001). Women in the under 35 age
      group had limited access to screening. Rates for biopsy and detected cancers were
      low. Women reported positive attitudes to mammography, with few reported
      barriers. Contrary to previous studies, there was no evidence that anxiety about
      breast cancer impedes uptake of health surveillance methods. Genetic counseling
      had a positive impact on management of breast cancer risk. Whether this
      translates into future health gains remains to be established.

PMID- 15943559
TI  - Application of a synthetic phage antibody library (ETH-2) for the isolation of
      single chain fragment variable (scFv) human antibodies to the pathogenic isoform
      of the hamster prion protein (HaPrPsc).
AB  - To overcome the limitation represented by the poor immunogenicity of prion
      protein (PrP) for conventional monoclonal antibodies preparation, we adopted an
      antibody phage display strategy to isolate specific human single chain fragment
      variable (scFv) directed towards the pathogenic isoform of the hamster prion
      protein (HaPrPsc). Phage-displaying HaPrPsc reactive scFvs were obtained after
      three rounds of selection of the ETH- 2 synthetic antibody library on HaPrPsc
      coated immunotubes and subsequent amplification in TG1 E. coli cells. These phage
      antibodies bind in ELISA to HaPrPsc and do not cross-react with the recombinant
      hamster prion protein (rHaPrP). Sequence analyses of the gene encoding for the
      antibody fragments and antigen recognition patterns determined by flow-cytometry
      on lymphoid cells indicate that the selected scFv recognize distinct epitopes in
      the PrPsc molecule. The results of this study demonstrate that display of scFvs
      on filamentous phage offers the possibility of producing phage antibodies showing
      immunoglobulin-like functions using only in vitro procedures, thus overcoming
      limitations of conventional hybridoma technology.

PMID- 15943560
TI  - Development of a delivery system for the continuous endogenous release of an anti
      idiotypic antibody against ovarian carcinoma.
AB  - The treatment of several cancers with anti-idiotype antibodies has shown
      promising results in animals and clinical trials. A common drawback of many anti
      idiotypic antibodies is their low immunogenicity. The aim of this work was to
      construct a new delivery form for the anti-idiotypic antibody ACA125hFc, with the
      goal of improving its immunogenicity as vaccine against ovarian carcinoma.
      Designed on bioencapsulation technologies, we generated an in vitro depot that
      acts as a continuous delivery system for the anti-idiotypic antibody ACA125hFc.
      C2C12 myoblasts were transfected with the anti-idiotypic chimeric antibody
      ACA125hFc, which mimics the CA125 tumor antigen and which consists of variable
      regions of the monoclonal murine antibody ACA125 (currently in clinical trial)
      and the human IgG Fc domain. Recombinant myoblasts were encapsulated in 1-cm
      semipermeable, polyethersulfone (PES), or polyvinylidene difluoride (PVDF) hollow
      fibers, which differ in their molecular weight cutoff (MWCO). Encapsulated cells
      were evaluated in vitro for viability and antibody secretion over a period of 3
      months. PES hollow fibers with a higher MWCO showed a twofold higher secretion
      rate of chACA125hFc compared to PES devices with a lower MWCO. No remarkable
      level of ACA125hFc could be detected for PVDF devices. The expression levels of
      the anti-idiotypic antibody ACA125hFc from capsules with a lower MWCO could be
      improved substantially, in both PES as well as PVDF, by inserting an internal
      polyethyleneterephtalate (PET) yarn. We conclude that murine recombinant C2C12
      myoblasts encapsulated in PES as well as PVDF hollow fibers containing an
      internal PET matrix can act as a long-term secretion system for anti-idiotypic
      antibodies.

PMID- 15943561
TI  - Preparation and characterization of a specific monoclonal antibody against
      CIAPIN1.
AB  - Cytokine-induced antiapoptosis inhibitor 1 (CIAPIN1) is a newly identified
      antiapoptosis molecule and a mediator of gastric MDR. We cloned cDNA of human
      CIAPIN1 by RT-PCR and constructed prokaryotic expression vectors of human CIAPIN1
      by inserting human CIAPIN1 coding region into pET28-a(+) and pGEX- 4T-1,
      respectively. The fusion proteins were expressed in Escherichia coli and purified
      by affinity chromotography. Monoclonal antibody (MAb) against CIAPIN1 was
      obtained with standard cell fusion technique and ELISA screening.
      Immunohistochemistry and Western blot showed that the anti-CIAPIN1 MAb recognizes
      human and mouse CIAPIN1 protein in both native and denatured form. Western
      blotting confirmed that the expression of CIAPIN1 was upregulated in MDR gastric
      cancer cell lines. This MAb will be a useful tool for the detection of CIAPIN1
      protein in future studies.

PMID- 15943562
TI  - Preparation and characterization of a monoclonal antibody against mannoprotein of
      Candida albicans.
AB  - BALB/c mice were immunized via injection with whole cell of Candida albicans
      serotype A. The spleens were fused with myeloma cells of SP2/0 origin. A
      mannoprotein-reactive monoclonal antibody (MAb) was selected and characterized by
      ELISA technique. This MAb reacted with strains of Candida such as C. albicans, C.
      tropicalis, and C. albicans of the Persian Type Culture Collection (PTCC).
      However, our antibody did not react with other Candida species such as C.
      parapsilosis, C. glabrata, C. stellatoidae, C. lusitania, C. krusei, and S.
      cervisiae. These antibodies also did not recognize extracts of other fungal
      species such as Aspergillus fumigatus and Aspergillus flavus, and bacterial
      strains such as Staphylococcus aureus and Pseudomonas aeruginosa. Polyclonal
      antibody produced in this study could not differentiate the above species and was
      reactive towards all fungal species mentioned above except bacterial strains of
      S. aureus and P. aeruginosa. Western blot analysis of ligand affinity-purified
      mannoproteins of C. albicans wall protein using this MAb showed reactivity toward
      a single protein band in the region of 55-65 kDa molecular weight. The same
      antibody, when examined with unpurified C. albicans extract, reacted with a broad
      band in the region of 55-105 kDa, which we concluded was due to a possible
      different glycosylation pattern of mannoprotein in crude extract in which the
      higher molecular weight protein was eliminated by ligand-binding affinity
      purification.

PMID- 15943563
TI  - Generation and characterization of a panel of monoclonal antibodies specific for
      human fibroblast growth factor receptor 4 (FGFR4).
AB  - Fibroblast growth factor receptor 4 (FGFR4) is a member of the FGFR family of
      receptor tyrosine kinases, and plays important roles in a variety of biological
      functions such as cell proliferation, differentiation, migration, angiogenesis,
      tissue repair, and tumorigenesis. The human FGFRs share a high degree of sequence
      homology between themselves, as well as with their murine homologs. Consequently,
      it has been suggested that it may be difficult to prepare monoclonal antibodies
      (MAbs) that are specific for the individual receptor types. In this
      communication, we report on the development and characterization of a panel of
      anti-human FGFR4 MAbs that were generated in mice using a rapid immunization
      protocol. Using a modified rapid immunization at multiple sites (RIMMS) protocol
      with the soluble extracellular domain of human FGFR4 (FGFR4-ECD), the immunized
      mice developed high levels of polyclonal IgG to the immunogen within 13 days of
      the first immunization. The lymph node cells isolated from the immunized animals
      were then fused with mouse myeloma cells for hybridoma generation. Use of an
      efficient hybridoma cloning protocol in combination with an ELISA screening
      procedure allowed for early identification of stable hybridomas secreting
      antihuman FGFR4 IgG. Several identified MAbs specifically reacted with the FGFR4
      protein without binding to the other human isoforms (FGFR1, FGFR2, and FGFR3). As
      evaluated by BIAcore analysis, most anti-FGFR4 MAbs displayed high affinities
      (8.6 x 10(8) approximately 3.9 x 10(10) M) to FGFR4. Furthermore, these MAbs were
      able to bind to FGFR4 expressed on human breast tumor cell lines MDA-MB-361 and
      MDA-MB-453. Taken together, the results demonstrate that the RIMMS strategy is an
      effective approach for generating class-switched, high-affinity MAbs in mice to
      evolutionarily conserved proteins such as human FGFR4. These MAbs may be useful
      tools for further investigation of the biological functions and pathological
      roles of human FGFR4.

PMID- 15943564
TI  - Production and characterization of a monoclonal antibody specific for NS3
      protease and the ATPase region of Dengue-2 virus.
AB  - Dengue is considered a reemerging disease of worldwide distribution. The Dengue
      virus non-structural protein 3 (NS3) is known to possess ATPase, helicase, and
      protease activities that are a constitutive part of the replication complex of
      Dengue virus. In this report, we discuss the cloning, expressing, and purifying
      of the Dengue-2 NS3 protein, to immunize mice and then generate monoclonal
      antibodies (MAbs). Our results show the production of MAbs specific to NS3
      protein of Dengue-2 virus, which by immunofluorescence recognize the native
      protein in experimentally infected endothelial cells (HMEC). Likewise, C6/36
      infected lisates were used in Western blots, and observed the specific
      characteristic band that defines the NS3 protein. We conclude that these
      antibodies may be a useful tool, not only to study the replicative process of
      Dengue virus, but also to generate specific diagnostic tools for Dengue
      infection.

PMID- 15943566
TI  - Prevalence and molecular characterization of human T cell leukemia virus type 2
      in a group of intravenous drug users coinfected with HIV type 1 in Portugal.
AB  - Human T cell lymphotropic virus type 2 infections can be found in the large urban
      areas of the United States and Europe, where Spain and Italy are the most
      affected countries. The population most affected by the epidemic is characterized
      by high-risk behavior groups, mainly the sharing of needles between intravenous
      drug users (IDUs) with contaminated cellular blood products. It is also described
      that HTLV-2 infection appears as a coinfection with HIV-1. We have selected
      samples corresponding to 583 IDUs infected with HIV and screened for the presence
      of HTLV-1/2 antibodies. We have performed the molecular characterization of HTLV
      2 in three confirmed positive cases on the basis of the long terminal repeat
      region. We can observe the Portuguese sequences (PortHl, PortNn, and PortVs) in
      the HTLV-2b cluster, grouping with the Spanish sequences, showing close
      phylogenetic relatedness. We may assume that HTLV-2 infection was introduced in
      Portugal from Spain. These results update previous reports that mentioned
      Portugal as being free of HTLV- 2 infections, and allow the identification of the
      subtype that is present, giving a first-hand description of the prevalence of
      HTLV-2 infection in a particular high-risk behavior group and justifying the
      importance of epidemiological surveillance in order to prevent dissemination of
      the infection.

PMID- 15943567
TI  - Seroprevalence and risk factors for human T cell lymphotropic virus type 1 and 2
      infection in human immunodeficiency virus-infected patients attending AIDS
      referral center health units in Londrina and other communities in Parana, Brazil.
AB  - The municipality of Londrina ranks second in the number of AIDS cases in the
      state of Parana, Brazil, with the Ministry of Health notified of 1070 cases from
      1984 to 2002. The aim of this study was to determine the seroprevalence and risk
      factors for HTLV-1/2 infection in HIV-infected patients attending the AIDS
      Reference Center serving Londrina (and surrounding region), Parana, Brazil. Data
      concerning sociodemographic conditions and risk factors were collected from 784
      HIV-infected patients, using a questionnaire. Blood samples were obtained from
      758 of the patients and subjected to serologic screening tests for the
      determination of HTLV-1/2, as well as hepatitis B virus (HBV), hepatitis C virus
      (HCV), and syphilis. Most patients were white (mean age, 35.9 years); 55.9% were
      males and 44.1% were females. The most frequent sexually transmitted disease was
      gonorrhea (28.5%), followed by syphilis (14.3%) and condyloma (12.2%). The major
      risk factors associated with the acquisition of retroviruses were sexual contact
      (84.8%) and intravenous drug use (IDU, 11.9%). The overall infection
      seroprevalence was 6.4% for HTLV-1/2, 37.2% for HBV, 21.0% for HCV, and 24.4% for
      syphilis. HTLV-1 and HTLV-2 infections were confirmed in 0.8 and 4.9% of
      patients, respectively. HIV/HTLV-1/2 coinfection was more frequent in IDUs (59.2%
      of cases) and was strongly associated with HCV (22.60 [95% CI, 10.35-49.35]). A
      weak association with HBV (2.09 [95% CI, 1.13-3.90]) and no association with
      syphilis were observed. The results showed that human retroviruses are
      circulating in southern Brazil, mainly among white people of both genders of low
      socioeconomic conditions and educational level. Although the sexual route was
      considered to be the major risk factor for HIV infection, HTLV-1/2 infection was
      strongly associated with IDU.

PMID- 15943568
TI  - Lowering the dose of hydroxyurea minimizes toxicity and maximizes anti-HIV
      potency.
AB  - The goal of this study was to optimize the hydroxyurea dosage in HIV-infected
      patients, and to minimize the toxicity and maximize the antiviral efficacy of the
      hydroxyurea-didanosine combination. In a randomized, open-label study (RIGHT 702,
      a multicenter trial performed in private and institutional practices), three
      daily doses (600 microg, 800-900 microg, and 1200 microg) of hydroxyurea were
      administered in combination with didanosine and stavudine to 115 chronically HIV
      infected patients, one-third antiretroviral drug naive, with viremia between 5000
      and 200,000 copies/ml regardless of CD4+ cell count. The primary efficacy end
      point was the proportion of patients with plasma HIV-1 RNA levels below 400
      copies/ml after 24 weeks of therapy. In the RIGHT 702 intent-to-treat population
      the lowest (600 mg) dose of hydroxyurea was better tolerated, associated with
      fewer adverse events, and more potent by all efficacy parameters, including the
      primary end point (76 versus 60% patients with viremia<400 copies/ml at week 24
      for the 600-mg and 800- to 900-mg dose groups, respectively; p=0.027), the mean
      area under the curve (60.3 versus 65.8; p=0.016), and the mean log10 decrease (
      1.95 versus -0.77; p=0.001). Patients receiving 600 mg of hydroxyurea daily also
      had the highest CD4+ cell count, CD4+/CD8+ cell ratio, and lowest CD8+ cell count
      and percentage (p=0.035). The RIGHT 702 trial provides an explanation for the
      increased toxicity and decreased efficacy of hydroxyurea when it was used at high
      dosage (1200 mg daily). At the optimal dosage of 600 mg daily, hydroxyurea, in
      combination with didanosine, deserves reevaluation for the long-term management
      of HIV/AIDS worldwide, because of its excellent resistance profile, durability,
      and affordability.

PMID- 15943569
TI  - Human T lymphotropic virus type 1 accessory protein p12I modulates calcium
      mediated cellular gene expression and enhances p300 expression in T lymphocytes.
AB  - Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T cell
      leukemia/lymphoma (ATLL), an aggressive CD4+ T lymphocyte malignancy. Activation
      of T lymphocytes is required for effective retroviral integration into the host
      cell genome and subsequent viral replication, but the molecular mechanisms
      involved in HTLV-1-mediated T cell activation remain unclear. HTLV-1 encodes
      various accessory proteins such as p12I, which has been demonstrated to be
      critical for HTLV-1 infectivity in vivo in rabbits and in vitro in quiescent
      primary human T lymphocytes. This hydrophobic protein localizes in the
      endoplasmic reticulum, increases intracellular calcium, and activates nuclear
      factor of activated T cell-mediated transcription. To further elucidate the role
      of p12I in regulation of cellular gene expression, we performed gene array
      analysis on stable p12I-expressing Jurkat T cells, using Affymetrix U133A arrays.
      Our data indicate that p12I altered the expression of genes associated with a
      network of interrelated pathways including T cell signaling, cell proliferation,
      and apoptosis. Expression of several calcium-regulated genes was found to be
      altered by p12I, consistent with known properties of the viral protein. Gene
      array findings were confirmed by semiquantitative RT-PCR in Jurkat T cells and
      primary CD4+ T lymphocytes. Furthermore, dose-dependent expression of p12I in
      Jurkat T cells resulted in significant increases in p300 and p300-dependent
      transcription. This is the first report of a viral protein influencing the
      transcription of p300, a rate-limiting coadapter critical in HTLV-1-mediated T
      cell activation. Collectively, our data strongly indicate that HTLV-1 p12I
      modulates cellular gene expression patterns to hasten the activation of T
      lymphocytes and thereby promote efficient viral infection.

PMID- 15943570
TI  - Viral dynamics and CD4+ T cell counts in subtype C human immunodeficiency virus
      type 1-infected individuals from southern Africa.
AB  - Defining viral dynamics in natural infection is prognostic of disease progression
      and could prove to be important for vaccine trial design as viremia may be a
      likely secondary end point in phase III HIV efficacy trials. There are limited
      data available on the early course of plasma viral load in subtype C HIV-1
      infection in Africa. Plasma viral load and CD4+ T cell counts were monitored in
      51 recently infected subjects for 9 months. Individuals were recruited from four
      southern African countries: Zambia, Malawi, Zimbabwe, and South Africa and the
      median estimated time from seroconversion was 8.9 months (interquartile range,
      5.7-14 months). All were infected with subtype C HIV-1 and median viral loads,
      measured using branched DNA, ranged from 3.82-4.02 log10 RNA copies/ml from 2-24
      months after seroconversion. Viral loads significantly correlated with CD4+ cell
      counts (r=-0.5, p<0.0001; range, 376-364 cells/mm3) and mathematical modeling
      defined a median set point of 4.08 log10 (12 143 RNA copies/ml), which was
      attained approximately 17 months after seroconversion. Comparative measurements
      using three different viral load platforms (bDNA, Amplicor, and NucliSens)
      confirmed that viremia in subtype C HIV-1-infected individuals within the first 2
      years of infection did not significantly differ from that found in early subtype
      B infection. In conclusion, the course of plasma viremia, as described in this
      study, will allow a useful baseline comparator for understanding disease
      progression in an African setting and may be useful in the design of HIV-1
      vaccine trials in southern Africa.

PMID- 15943571
TI  - Comparison of whole gene and whole virus scrambled antigen approaches for DNA
      prime and fowlpox virus boost HIV type 1 vaccine regimens in macaques.
AB  - T cell immunity plays a critical role in controlling HIV-1 viremia, and encoding
      a limited set of HIV-1 genes within DNA and poxvirus vectors can, when used
      sequentially, induce high levels of T cell immunity in primates. However, a
      limited breadth of T cell immunity exposes the host to potential infection with
      either genetically diverse HIV-1 strains or T cell escape variants of HIV-1. In
      an attempt to induce maximally broad immunity, we examined DNA and recombinant
      fowlpox virus (rFPV) vaccines encoding all HIV-1 genes derived from a global HIV
      1 consensus sequence, but expressed as multiple overlapping scrambled 30-amino
      acid segments (scrambled antigen vaccines, or SAVINEs). Three groups of seven
      pigtail macaques were immunized with sets of DNA and rFPV expressing Gag/Pol
      antigens only, the whole genome SAVINE antigens, or no HIV-1 antigens and T cell
      immunity was monitored by ELISpot and intracellular cytokine staining. High
      levels of cross-subtype HIV-specific T cell immunity to Gag were consistently
      induced in the seven macaques primed with DNA and rFPV vaccines expressing
      Gag/Pol as intact proteins. It was, however, difficult to repeatedly boost
      immunity with further rFPV immunizations, presumably reflecting high levels of
      anti- FPV immunity. Unfortunately, this vaccine study did not consistently
      achieve a broadened level of T cell immunity to multiple HIV genes utilizing the
      novel whole-virus SAVINE approach, with only one of seven immunized animals
      generating broad T cell immunity to multiple HIV-1 proteins. Further refinements
      are planned with alternative vector strategies to evaluate the potential of the
      SAVINE technology.

PMID- 15943572
TI  - HIV type 1 genotypic variation in an antiretroviral treatment-naive population in
      southern India.
AB  - Most studies of HIV-1 drug resistance have examined subtype B viruses; fewer data
      are available from developing countries, where non-B subtypes predominate. We
      determined the prevalence of mutations at protease and reverse transcriptase drug
      resistance positions in antiretroviral drug-naive individuals in southern India.
      The pol region of the genome was amplified from plasma HIV-1 RNA in 50 patients.
      All sequences clustered with HIV-1 subtype C. All patients had at least one
      protease and/or RT mutation at a known subtype B drug resistance position. Twenty
      percent of patients had mutations at major protease inhibitor resistance
      positions and 100% had mutations at minor protease inhibitor resistance
      positions. Six percent and 14% of patients had mutations at nucleoside reverse
      transcriptase inhibitor and/or nonnucleoside reverse transcriptase inhibitor
      resistance positions, respectively. Larger scale studies need to be undertaken to
      better define the genotypic variation of circulating Indian subtype C viruses and
      their potential impact on drug susceptibility and clinical outcome in treated
      individuals.

PMID- 15943574
TI  - New two-amino acid insertion near codon 70 of the HIV type 1 protease gene.
AB  - A two-amino acid insertion near codon 70 of the HIV-1 protease gene was found in
      an individual failing protease inhibitor therapy. Susceptibility of this strain
      to protease inhibitors was similar to that of non-insert-containing strains with
      comparable resistance mutations and one or more other major PI mutations.

PMID- 15943573
TI  - High genetic diversity of human immunodeficiency virus type 1 in Angola.
AB  - To investigate which HIV-1 genetic forms are circulating in Angola, we have
      determined the gag and/or env genotypes of 48 isolates from patients living in
      Cabinda and Luanda provinces. The following subtypes were identified: A1 (18
      samples, 38%), C (7, 15%), H (5, 10%), J (3, 6%), G (2, 4%), A2 (2, 4%), F1 (1,
      2%), and D (1, 2%). The env gene fragment was untypable in one sample. Discordant
      subtype classifications in the gag and env genes were found in eight (17%)
      samples. There were six different recombination patterns (gag/env): A1/H (3, 6%),
      A1/G (1, 2%), C/A2 (1, 2%), F1/B (1, 2%), G/B (1, 2%), and G/H (1, 2%). The A1/H
      recombinant may represent a new circulating recombinant form. The marked genetic
      heterogeneity of HIV-1 in Angola has important implications for vaccine
      development.

PMID- 15943575
TI  - Characterization of intersubtype recombinant HIV type 1 genomes using a
      nonradioactive heteroduplex tracking assay.
AB  - The HIV-1 epidemic is characterized by the dominance of distinct viral subtypes
      in different regions of the world, and intersubtype recombinants are common.
      Traditional subtyping methods analyze only a small fragment of the HIV-1 genome,
      so the true extent of diversity and recombination has been difficult to examine.
      We developed a heteroduplex tracking assay (HTA) to identify viral subtypes and
      rapidly detect recombinant HIV-1 genomes. By using probes that target seven
      regions across the HIV-1 genome, HTAs can identify intersubtype recombinants on
      the basis of the heteroduplex mobility pattern. We used this method to analyze
      HIV-1 strains from 12 patients from the United States and Kenya, comparing the
      results with those obtained by sequencing. HTA analysis correctly identified the
      subtype of each region of the genome, revealing that several isolates were
      recombinants. This method is suitable for studies of HIV-1 diversity and
      recombination in areas of the world where multiple subtypes are found.

PMID- 15943576
TI  - Genetic linkage of nevirapine resistance mutations in HIV type 1 seven days after
      single-dose nevirapine.
AB  - The HIVNET 012 trial in Uganda demonstrated that a regimen of single-dose
      nevirapine (NVP) can prevent HIV-1 mother-to-child transmission. Previous studies
      show that HIV-1 with one or more NVP resistance (NVPR) mutations can be selected
      in many women as early as 7 days after single-dose NVP. We evaluated the genetic
      linkage of NVPR mutations in plasma from women in HIVNET 012 collected 7 days
      after single-dose NVP administration. The HIV-1 pol region was amplified and
      cloned from 20 plasma samples (16 with NVPR mutations detected by population
      sequencing and 4 with no NVPR mutations detected), and 10 clones from each sample
      were sequenced. Up to five different NVPR mutations were detected in clones from
      a single sample. K103N and Y181C were the most common mutations detected. Clones
      with two genetically linked mutations were detected in four samples. Different
      combinations of NVPR mutations were linked in individual clones, but none of the
      clones contained both K103N and Y181C. Further studies are needed to evaluate
      whether selection of minority variants with one or more NVPR mutations after
      single-dose NVP is clinically relevant.

PMID- 15943577
TI  - Phylogenetic heterogeneity of new HTLV type 1 isolates from southern India in
      subgroup A.
AB  - Seven isolates of human T cell leukemia virus type 1 (HTLV-1) were taken in
      southern India and phylogenetically analyzed to gain new insights into the origin
      and dissemination of HTLV-1 in the subcontinent. The new Indian HTLV-1s were
      found to be members of subgroup A (Transcontinental subgroup) of the Cosmopolitan
      group. They formed three different clusters (South African/Caribbean, Middle
      Eastern, and East Asian clusters). These results demonstrate that Indian HTLV-1s
      are genetically heterogeneous and include the most divergent strain of subgroup
      A. On the basis of these results, we speculate that subgroup A HTLV- 1s may have
      been present for thousands of years in India.

PMID- 15943578
TI  - Postprandial acylated ghrelin status following fat and protein manipulation of
      meals in healthy young women.
AB  - The aim of the present study was to investigate the postprandial effect of diet
      composition on circulating acylated ghrelin levels in healthy women. A randomized
      cross-over study of three experimental treatments was performed. A total of 11
      healthy young women of normal body weight completed the study. All 11 subjects
      consumed three iso-energetic meals of different macronutrient composition, a
      balanced meal (50% carbohydrates, 30% fat and 20% protein), a high-fat meal (45%
      carbohydrates, 45% fat and 10% protein) and a high-protein meal (45%
      carbohydrates, 20% fat and 35% protein), for breakfast on separate days. The test
      meals were administered 1 month apart. Blood samples were withdrawn immediately
      before and at 15, 30, 60, 120 and 180 min after the test meal for measurement of
      plasma acylated ghrelin, as well as serum glucose, insulin and triacylglycerol
      (triglyceride) levels. Acylated ghrelin fell significantly after ingestion of
      both the balanced and high-protein meals. Ghrelin persisted at significantly
      lower levels than baseline for a longer duration following the high-protein meal
      (P<0.05 at 15, 30, 60 and 120 min) compared with the balanced meal (P<0.05 at 30
      and 60 min). Moreover, acylated ghrelin levels correlated negatively with the
      postprandial insulin levels. In conclusion, postprandial changes in acylated
      plasma ghrelin depend on the macronutrient composition of the meal and are
      possibly influenced by insulin.

PMID- 15943579
TI  - Purification of transferrin from Cohn supernatant I using ion-exchange
      chromatography.
AB  - The present paper describes an anion-exchange chromatography method to separate
      iron-free apo-Tf (apo-transferrin) from albumin and IgG in Cohn supernatant I.
      The method uses DEAE-fast flow Sepharose chromatography along with optimized
      protein concentration (5%, w/v) and column operation conditions (40 g/l,
      conductivity <1.0 mS/cm) to resolve apo-Tf from IgG and albumin. The single step
      purifies apo-Tf to >90% and provides an efficient means to obtain commercial
      quantities of the protein.

PMID- 15943580
TI  - Sphingomyelins suppress the targeted disruption of lysosomes/endosomes by the
      photosensitizer NPe6 during photodynamic therapy.
AB  - Recent studies have described a biochemical pathway whereby lysosome disruption
      and the released proteases initiate the intrinsic apoptotic pathway. Irradiation
      of murine hepatoma 1c1c7 cells preloaded with the lysosomal photosensitizer NPe6
      (N-aspartyl chlorin e6) caused a rapid loss of Acridine Orange staining of acidic
      organelles, release of cathepsin D from late endosomes/lysosomes and the
      activation of procaspase-3. Pretreatment of NPe6-loaded cultures with 10-50
      microM 3-O-MeSM (3-O-methylsphingomyelin) caused a concentration-dependent
      suppression of apoptosis following irradiation. This suppression reflected a
      stabilization of lysosomes/endosomes, as opposed to an inhibition of the
      accumulation of photosensitizer in these organelles. Exogenously added
      sphingomyelin, at comparable concentrations, offered some protection, but less
      than 3-O-MeSM. Fluorescence microscopy showed that 3-O-MeSM competed with NBD-C6
      sphingomyelin (6-{[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]hexanoyl}
      sphingosyl phosphocholine) for co-localization with LysoTracker Red in acidic
      organelles. Pre-treatment of 1c1c7 cultures with 3-O-MeSM also suppressed the
      induction of apoptosis by TNFalpha (tumour necrosis factor alpha), but offered no
      protection against HA14-1 [ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)
      4H-chromene-3-carboxylate], staurosporine, tunicamycin or thapsigargin. These
      results suggest that exogenously added 3-O-MeSM is trafficked to and stabilizes
      late endosomes/lysosomes against oxidant-induced damage, and further implicate a
      role for lysosomal proteases in the apoptotic processes initiated by TNFalpha and
      lysosomal photosensitizers.

PMID- 15943581
TI  - Unravelling the structure of the pneumococcal autolytic lysozyme.
AB  - The LytC lysozyme of Streptococcus pneumoniae forms part of the autolytic system
      of this important pathogen. This enzyme is composed of a C-terminal CM (catalytic
      module), belonging to the GH25 family of glycosyl hydrolases, and an N-terminal
      CBM (choline-binding module), made of eleven homologous repeats, that
      specifically recognizes the choline residues that are present in pneumococcal
      teichoic and lipoteichoic acids. This arrangement inverts the general assembly
      pattern of the major pneumococcal autolysin, LytA, and the lytic enzymes encoded
      by pneumococcal bacteriophages that place the CBM (made of six repeats) at the C
      terminus. In the present paper, a three-dimensional model of LytC built by
      homology modelling of each module and consistent with spectroscopic and
      hydrodynamic studies is shown. In addition, the putative catalytic-pair residues
      are identified. Despite the inversion in the modular arrangement, LytC and the
      bacteriophage-encoded Cpl-1 lysozyme most probably adopt a similar global fold.
      However, the distinct choline-binding ability and their substrate-binding
      surfaces may reflect a divergent evolution directed by the different roles played
      by them in the host (LytC) or in the bacteriophage (Cpl-1). The tight binding of
      LytC to the pneumococcal envelope, mediated by the acquisition of additional
      choline-binding repeats, could facilitate the regulation of the potentially
      suicidal activity of this autolysin. In contrast, a looser attachment of Cpl-1 to
      the cell wall and the establishment of more favourable interactions between its
      highly negatively charged catalytic surface and the positively charged chains of
      pneumococcal murein could enhance the lytic activity of the parasite-encoded
      enzyme and therefore liberation of the phage progeny.

PMID- 15943582
TI  - Mutating His29, His125, His133 or His158 abolishes glycosylphosphatidylinositol
      specific phospholipase D catalytic activity.
AB  - Glycosylphosphatidylinositol (GPI)-specific phospholipase D (GPI-PLD)
      specifically cleaves GPIs. This phospholipase D is a secreted protein consisting
      of two domains: an N-terminal catalytic domain and a predicted C-terminal b
      propeller. Although the biochemical properties of GPI-PLD have been extensively
      studied, its catalytic site has not been identified. We hypothesized that a
      histidine residue(s) may play a critical role in the catalytic activity of GPI
      PLD, based on the observations that (i) Zn2+, which utilizes histidine residues
      for binding, is required for GPI-PLD catalytic activity, (ii) a phosphohistidine
      intermediate is involved in phospholipase D hydrolysis of phosphatidylcholine,
      (iii) computer modelling suggests a catalytic site containing histidine residues,
      and (iv) our observation that diethyl pyrocarbonate, which modifies histidine
      residues, inhibits GPI-PLD catalytic activity. Individual mutation of the ten
      histidine residues to asparagine in the catalytic domain of murine GPI-PLD
      resulted in three general phenotypes: not secreted or retained (His56 or His88),
      secreted with catalytic activity (His34, His81, His98 or His219) and secreted
      without catalytic activity (His29, His125, His133 or His158). Changing His133 but
      not His29, His125 or His158 to Cys resulted in a mutant that retained catalytic
      activity, suggesting that at least His133 is involved in Zn2+ binding. His133 and
      His158 also retained the biochemical properties of wild-type GPI-PLD including
      trypsin cleavage pattern and phosphorylation by protein kinase A. Hence, His29,
      His125, His133 and His158 are required for GPI-PLD catalytic activity.

PMID- 15943583
TI  - Development of a novel serum-free freezing medium for mammalian cells using the
      silk protein sericin.
AB  - Cryopreservation is a pivotal process in cellular engineering for creating a
      continuous source of generated functional cell lines and for the convenience of
      various medical treatments that involve cell culture. FBS (fetal bovine serum)
      supplemented with 10% (v/v) DMSO is extensively used as a freezing medium for
      mammalian cells using conventional methods. However, FBS should ideally be
      avoided, owing to serious concerns regarding bovine spongiform encephalopathy and
      other infections such as viruses, and an alternative to FBS is eagerly awaited.
      Furthermore, bio-medicines and cells for transplantation should not be
      infectious. The present study aimed to develop a novel serum-free freezing
      medium. For this purpose, we focused on using the silk protein sericin as a
      cryoprotectant for storage and developed a novel serum-free freezing medium
      consisting of PBS, 1% (v/w) sericin, 0.5% (v/w) maltose, 0.3% (v/w) proline, 0.3%
      (v/w) glutamine and 10% DMSO. This novel freezing medium was compared with the
      conventional FBS supplemented with DMSO and also with three purchased freezing
      media with respect to cryopreservation of the P 3 U1 myeloma cell line and
      Chinese-hamster ovary cells. As a result, the constructed medium containing
      sericin successfully cryopreserved both cell types as efficiently as the
      conventional medium of FBS containing 10% DMSO and was superior to all three of
      the purchased media. The constructed medium containing sericin also cryopreserved
      normal human dermal fibroblasts, human epidermal keratinocytes, the rat
      phaeochromocytoma cell line PC12 and insect (Spodoptera frugiperda) cell line S f
      9 as effectively as the conventional medium of FBS and DMSO.

PMID- 15943584
TI  - Novel inhibitors of fatty-acid synthase from green tea (Camellia sinensis Xihu
      Longjing) with high activity and a new reacting site.
AB  - Recent studies have shown that FAS (fatty acid synthase) is a potential
      therapeutic target of obesity. In the present paper we report that extract of
      green tea (Camellia sinensis Xihu Longjing) inhibits FAS effectively with an IC50
      value of 12.2 microg dry weight/ml. The ability of GTE (green tea extract) to
      inhibit FAS is more potent than that of two known inhibitors in green tea leaves,
      EGCG (epigallocatechin gallate) and ECG (epicatechin gallate). We find that (-)
      CG (catechin gallate) is a very potent inhibitor of FAS, with an IC50 of 1.5
      microg/ml, and may contribute to the high inhibitory effect of GTE on FAS. The
      inhibitory mechanism of (-)-CG is not mainly involved in its binding to the beta
      oxoacyl reductase domain to which both (-)-EGCG and (-)-ECG mainly bind. By
      analyses of the inhibitory kinetics and the structure of the gallated catechins,
      we found that the acyl transferase domain may be the main site reacting with (-)
      CG, the structure consisting of a B ring, a C ring and a gallate ring, which is
      possibly essential for its inhibitory efficacy. The polyphenols rather than the
      alkaloids are the main fractions contributing to the inhibitory effect of GTE on
      FAS. During separation we also found that the total ability of this portion to
      inhibit FAS increases by 15-fold, and this may be due to some novel potent
      inhibitor of FAS other than (-)-CG being formed.

PMID- 15943585
TI  - Rat liver betaine-homocysteine S-methyltransferase equilibrium unfolding:
      insights into intermediate structure through tryptophan substitutions.
AB  - Equilibrium folding of rat liver BHMT (betaine-homocysteine methyltransferase), a
      TIM (triosephosphate isomerase)-barrel tetrameric protein, has been studied using
      urea as denaturant. A combination of activity measurements, tryptophan
      fluorescence, CD and sedimentation-velocity studies suggested a multiphasic
      process including two intermediates, a tetramer (I4) and a monomer (J). Analysis
      of denaturation curves for single- and six-tryptophan mutants indicated that the
      main changes leading to the tetrameric intermediate are related to alterations in
      the helix alpha4 of the barrel, as well as in the dimerization arm. Further
      dissociation to intermediate J included changes in the loop connecting the C
      terminal alpha-helix of contact between dimers, disruption of helix alpha4, and
      initial alterations in helix alpha7 of the barrel, as well as in the dimerization
      arm. Evolution of the monomeric intermediate continued through additional
      perturbations in helix alpha7 of the barrel and the C-terminal loop. Our data
      highlight the essential role of the C-terminal helix in dimer-dimer binding
      through its contribution to the increased stability shown by BHMT as compared
      with other TIM barrel proteins. The results are discussed in the light of the
      high sequence conservation shown by betaine-homocysteine methyltransferases and
      the knowledge available for other TIM-barrel proteins.

PMID- 15943586
TI  - Defective insulin receptor activation and altered lipid rafts in Niemann-Pick
      type C disease hepatocytes.
AB  - Niemann-Pick type C (NPC) disease is a neuro-visceral cholesterol storage
      disorder caused by mutations in the NPC-1 or NPC-2 gene. In the present paper, we
      studied IR (insulin receptor) activation and the plasma-membrane lipid assembly
      in primary hepatocytes from control and NPC1-/- mice. We have previously reported
      that, in hepatocytes, IR activation is dependent on cholesterol-sphingolipid
      rafts [Vainio, Heino, Mansson, Fredman, Kuismanen, Vaarala and Ikonen (2002) EMBO
      Rep. 3, 95-100]. We found that, in NPC hepatocytes, IR levels were up-regulated
      and the receptor activation was compromised. Defective IR activation was
      reproduced in isolated NPC plasma-membrane preparations, which displayed an
      increased cholesterol content and saturation of major phospholipids. The NPC
      plasma membranes were less fluid than control membranes as indicated by increased
      DPH (1,6-diphenyl-1,3,5-hexatriene) fluorescence anisotropy values. Both in NPC
      hepatocytes and plasma-membrane fractions, the association of IR with low-density
      DRMs (detergent-resistant membranes) was increased. Moreover, the detergent
      resistance of both cholesterol and phosphatidylcholine were increased in NPC
      membranes. Finally, cholesterol removal inhibited IR activation in control
      membranes but restored IR activation in NPC membranes. Taken together, the
      results reveal a lipid imbalance in the NPC hepatocyte, which increases lipid
      ordering in the plasma membrane, alters the properties of lipid rafts and
      interferes with the function of a raft-associated plasma-membrane receptor. Such
      a mechanism may participate in the pathogenesis of NPC disease and contribute to
      insulin resistance in other disorders of lipid metabolism.

PMID- 15943587
TI  - Expression and immunolocalization of aquaporin-7 in rat gastrointestinal tract.
AB  - BACKGROUND INFORMATION: In the gastrointestinal tract of mammals, water can
      either be secreted with digestive juices or absorbed by the small and large
      intestine. Transcellular water movement can be mediated by the transmembrane
      protein family of AQPs (aquaporins), as has also been recently identified in the
      gastrointestinal tract. However, the localization, expression and functioning of
      AQPs in the gastrointestinal tract have not been completely characterized. For
      the present study, we investigated: (1) the expression of AQP7 in some portions
      of rat gastrointestinal tract by semiquantitative reverse transcriptase-PCR and
      by immunoblotting and (2) the cellular and subcellular localization of AQP7 by
      immunohistochemistry. RESULTS: AQP7 mRNA and proteins were highly expressed in
      the small intestine, weakly in the caecum, colon and rectum and were absent in
      the stomach. Immunoblotting analysis using rat gastrointestinal tract membrane
      fractions showed two major bands corresponding to a molecular mass of approx. 34
      and 40 kDa for the AQP7 protein. No bands were observed when the anti-AQP7
      antibody was preadsorbed with the immunizing peptide. Immunohistochemistry
      revealed strong AQP7 labelling in the surface epithelial cells of duodenum,
      jejunum, ileum, caecum, colon and rectum, whereas weak or no labelling was
      observed in the crypt cells. The labelling was manifest particularly in the
      apical membrane but intracellular staining was also observed. CONCLUSIONS: The
      results indicate that AQP7 is present in the small and large intestine. The
      higher expression of AQP7 protein at the apical pole of the superficial
      epithelial cells suggests its involvement in rapid fluid movement through the
      villus epithelium.

PMID- 15943588
TI  - Identification of a novel p300-specific-associating protein, PRS1
      (phosphoribosylpyrophosphate synthetase subunit 1).
AB  - CBP [CREB (cAMP-response-element-binding protein)-binding protein] and p300 play
      critical roles in transcriptional co-activation, cell differentiation,
      proliferation and apoptosis. Multiple transcription factors associate with
      CBP/p300. With the exception of the SYT oncoprotein, no proteins have been
      identified that specifically associate with p300, but not CBP. In the present
      study, we isolated a novel p300-associated protein for which no interaction with
      CBP was observed by GST (glutathione S-transferase) pull-down assay using Jurkat
      cell lysates metabolically labelled with [35S]methionine. This protein bound the
      KIX (kinase-inducible) domain of p300. Following resolution by two-dimensional
      acrylamide gel electrophoresis, we identified the KIX-domain-bound protein by MS
      analysis as PRS1 (phosphoribosylpyrophosphate synthetase subunit 1), a protein
      essential for nucleoside biosynthesis. This is the first report to demonstrate
      the existence of a p300 KIX-domain-specific-interacting protein that does not
      interact with CBP. Thus p300 may play a role in the regulation of DNA synthesis
      through interactions with PRS1.

PMID- 15943590
TI  - Hereditary angio-oedema in children: a management guideline.
AB  - Hereditary angio-oedema is an uncommon condition, which usually first presents in
      childhood. In the absence of appropriate treatment hereditary angio-oedema has a
      high mortality. There are a number of reports of successful short- and long-term
      treatment with individual agents in those who suffer from hereditary angio
      oedema. However, there is little guidance in the literature for the overall
      management of children and adolescents with this condition. Here we review the
      treatment options available for children and adolescents with hereditary angio
      oedema, and propose a simple management guideline for such patients.

PMID- 15943591
TI  - Frequency and potential cause of bronchus-associated lymphoid tissue in fetal
      lungs.
AB  - Bronchus-associated lymphoid tissue consists of lymphoid follicles with or
      without a germinal center within the bronchial wall. Bronchus-associated lymphoid
      tissue is part of the integrated mucosal immune system and present in about 50%
      of healthy infants. We examined a series of 141 fetal and neonatal lungs and
      detected bronchus-associated lymphoid tissue in 100% of cases with amniotic
      infection while postpartum perinatal pneumonia did not elicit bronchus-associated
      lymphoid tissue formation. Only rarely and in low density, bronchus-associated
      lymphoid tissue was present in non-infected fetuses. The in utero formation of
      bronchus-associated lymphoid tissue seems to be a reactive phenomenon and - as
      has been shown in another study - does not portend an adverse prognosis.

PMID- 15943592
TI  - The influence of intravenous hydrocortisone on cytokine levels in children with
      asthma.
AB  - Nocturnal airway obstruction occurs frequently in childhood asthma and results
      from increased airway inflammation. Lymphocytes are believed to be key effector
      cells of airway wall inflammation, releasing pro-inflammatory mediators and
      cytokines. A previous study showed that hydrocortisone infusion, an effective
      anti-inflammatory treatment, improves nocturnal and daytime FEV(1) values. This
      study in 16 children with moderate asthma was designed to assess whether there
      exists day and night differences in IL-4, IL-5, IL-8, and IFN-gamma production of
      concanavaline A stimulated peripheral blood mononuclear cells. Furthermore, we
      investigated whether substitution of low serum cortisol levels with intravenous
      hydrocortisone would affect those parameters. Saline (as a placebo) or
      hydrocortisone (30 microg/m(2) body surface area/24 h) was intravenously
      administered in a randomized, double blind, cross-over design. Measurements under
      saline or hydrocortisone infusions were separated by 1 wk. At 04:00 and 16:00
      hours 10 ml blood was taken for determination of peripheral blood mononuclear
      cell isolation and stimulation, and an eosinophil count. Hydrocortisone infusion
      significantly reduced the nocturnal fall in FEV(1). Median values of IFNgamma, IL
      4, IL-5, and IL-8 produced by peripheral blood mononuclear cells did not
      significantly differ at 04:00 and 16:00 hours, both with saline and
      hydrocortisone infusion. Our results suggest that FEV(1) improvement is not due
      to suppression of circulating peripheral blood mononuclear cell activation. We
      hypothesize that it is rather due to its effect on local lung tissue epithelial
      and/or fibroblasts thereby reducing airway inflammation and vascular leakage.

PMID- 15943593
TI  - Discrepant clinical responses and blood chemokine profiles between two non
      steroidal anti-inflammatory medications for children with mild persistent asthma.
AB  - In a randomized study, two oral medications, ketotifen and montelukast, were
      compared for children with mild persistent asthma. Montelukast revealed faster
      clinical responses than ketotifen, showing improved exhaled nitric oxide, peak
      expiratory flow, and asthma scores in 1 wk. After 8-wk of medication, both
      ketotifen and montelukast revealed improved clinical responses. However, 8 wk of
      ketotifen, but not montelukast, decreased plasma serum thymus and activation
      regulated chemokine (317.854 +/- 207.906 vs. 181.348 +/- 167.109, p < 0.05),
      macrophage-derived chemokine (355.11 +/- 174.30 vs. 169.19 +/- 62.42, p < 0.05)
      levels. In conclusion, different oral non-steroidal anti-inflammatory drugs
      revealed faster or slower treatment responses due to different mechanisms.

PMID- 15943594
TI  - Polymorphisms of the TGF-beta1 gene are not associated with bronchial asthma in
      Caucasian children.
AB  - The chromosomal region 19q13 has been found in linkage to allergic diseases in
      several genome-wide linkage screens. One candidate gene within this region is the
      gene coding for TGF-beta1. Transforming growth factor (TGF)-beta acts as an anti
      inflammatory cytokine suppressing allergic inflammation and hyper-reactivity.
      However, in ongoing inflammation of the lungs it can induce fibrosis and airway
      remodelling as seen in chronic asthma. Several polymorphisms within TGF-beta1
      have been identified and one, -C509T, has been shown to be in association with
      elevated immunoglobulin E levels and severe bronchial asthma in different
      populations. However, other studies failed to confirm the association. The
      present study investigated two polymorphisms within the gene coding for TGF
      beta1, -C509T and G915C, and for their potential association with bronchial
      asthma in Caucasian children. Genotyping of these polymorphisms was performed by
      means of restriction fragment length polymorphisms in a population of 231
      asthmatic children and a control population of 269 individuals. Statistical
      analyses made use of the Armitage's trend test. In addition haplotypes were
      calculated by arlequin. None of the two polymorphisms showed association with
      bronchial asthma. They were found to be in linkage disequilibrium. We conclude
      from our data that TGF-beta1 is unlikely to represent a major gene in the
      development of bronchial asthma in the Caucasian population.

PMID- 15943595
TI  - Modest increase in seasonal allergic rhinitis and eczema over 8 years among
      Estonian schoolchildren.
AB  - We studied time trends in the prevalence of asthma and allergic diseases in
      Estonian children born before and after the collapse of the Soviet Union, as this
      event markedly altered the lifestyle in Estonia. Two identical cross-sectional
      studies were performed as part of phase I and phase III of the International
      Study of Asthma and Allergies in Childhood (ISAAC). Children, aged 6-7 yr (n =
      3070 in 1993-94 and 2383 in 2001-02) and 13-14 yr (n = 3476 and 3576,
      respectively), completed ISAAC core-written questionnaires, and 13-14-yr olds (n
      = 3427 and 3259, respectively) also video questionnaires. The prevalence of
      respiratory symptoms was mostly similar in the two studies. Despite this, the
      prevalence of diagnosed asthma increased. This was probably due to modified
      diagnostic criteria and increased awareness. Furthermore, the prevalence of
      rhinitis during the pollen season increased, e.g., rhinitis in May from 1.7% to
      3.5%; sex-adjusted prevalence odds ratio (POR) 2.09 (95% confidence interval 1.47
      2.96) in 6-7-yr olds, and from 2.6% to 5.5%; POR 2.22 (1.72-2.87) in 13-14-yr
      olds. The prevalence of flexural dermatitis also increased from 12.0% to 13.5%;
      POR 1.20 (1.02-1.41) in 6-7-yr olds, and from 7.7% to 9.4%; POR 1.26 (1.07-1.50)
      in 13-14-yr olds. The increase was similar in children born before and after the
      regaining of Estonian independence, indicating that the influence of factors
      related to a Western lifestyle and affecting the prevalence of allergic symptoms
      is not restricted to infancy, but may be operative throughout childhood.

PMID- 15943596
TI  - The primary prevention of asthma in children study: design of a multifaceted
      prevention program.
AB  - The PREVASC study addresses the primary prevention of asthma in infants and small
      children. The objective of this study is to investigate whether a multifaceted
      prenatally started intervention strategy in high-risk infants leads to a decrease
      in the occurrence of (severe) asthma and whether a refinement of the prevention
      strategy leads to an increase in the adherence to the prevention program. The
      primary prevention program includes house dust mite impermeable bed coverings,
      education on breast feeding, hypoallergenic feeding, timing of introduction of
      solid food and smoking cessation. A total of 888 infants were prenatally
      included. By the time of inclusion the mothers were 3-7 months pregnant. About 27
      infants were excluded from the study and 18 dropped out. Of the remaining 843
      infants 535 had a first-degree familial predisposition of asthma (high-risk
      group), whereas a reference group of 308 (162 boys) infants was not predisposed
      for asthma in the first-degree (low-risk group). To evaluate the (cost
      )effectiveness of the preventive intervention, 222 (118 boys) infants of the high
      risk group allocated to the intervention group and 221 (112 boys) allocated to a
      control group are followed up. The low-risk infants served as controls to
      evaluate the predictive value of high risk (first-degree familial predisposition
      of asthma). The infants are followed from the prenatal stage until they reach the
      age of 6 yr. The remaining 92 high-risk infants were included in an optimized
      randomized-clinical adherence trial (RCAT). Of these 92 infants, 45 (20 boys)
      were allocated to an intervention group and 47 (24 boys) to a control group.
      Until now all infants have been followed for at least 1 yr.

PMID- 15943597
TI  - Comparison of quality of life between asthmatic and healthy school children.
AB  - There are only a few studies which have assessed the impact of asthma on the
      quality of life (QoL) compared to healthy children. In this study we wanted to
      compare QoL between asthmatic and healthy children in a population based setting.
      We surveyed 2159 children aged 11-15 yr with a Child Health Questionnaire; a
      generic QoL measure for children. This method gives a profile of the QoL
      consisting of 11 scales giving a range from 0 to 100. Asthma was defined based on
      the ISAAC questionnaire on asthma and asthma symptoms. In all, 192 children
      (8.9%) reported to have asthma diagnosed by a doctor and 61 of them (2.8% of all
      children) had been symptomatic during the previous month. Among these symptomatic
      children significantly impaired QoL was observed in 8 of the 11 scales compared
      to non-asthmatics. The most affected scales were those defining the physical part
      of child's QoL: Mean General Health scores were 60 for asthmatic and 74 for non
      asthmatic children and mean Bodily Pain scores 71 and 86, respectively. Symptoms
      during longer periods were associated with an overall decreased QoL. In
      conclusion, a child's asthma impairs the QoL and especially the physical
      dimensions.

PMID- 15943598
TI  - Immediate allergic reactions to cephalosporins and penicillins and their cross
      reactivity in children.
AB  - Penicillins and cephalosporins are the most important betalactams inducing IgE
      mediated reactions. The safety of administering cephalosporins to penicillin
      allergic children is a particular problem, because cephalosporin allergenic
      determinants have not been properly identified. A study was undertaken to
      evaluate the frequency of anaphylactic reactions to cephalosporins and
      penicillins and their cross-reactivity in a pediatric population. A prospective
      survey was conducted in a group of 1170 children with suspected immediate
      allergic reactions to cephalosporins and/or penicillins, which were examined
      during a period of 8 yr. In vivo (skin tests and challenges) and in vitro tests
      (for specific IgE) were performed with standard concentration of penicillins and
      cephalosporins. When 1170 children with a clinical history of allergy to
      penicillins and/or cephalosporins were tested in vivo for immediate
      hypersensitivity to betalactams, 58.3% cases overall were found to be skin or
      challenge test positive. Among them, 94.4% patients were positive to penicillins
      and 35.3% to cephalosporins. The frequency of positive reactions in the in vivo
      testing was in the range from 36.4% to 88.1% for penicillins and from 0.3% to
      29.2% for cephalosporins. However, 31.5% of the penicillin allergic children
      cross-reacted to some cephalosporin. If a child was allergic to a cephalosporin,
      the frequency of positive reactions to penicillin was 84.2%. The cross-reactivity
      between cephalosporins and penicillins varied between 0.3% and 23.9%. The cross
      reactivity among different generations of cephalosporins varied between 0% and
      68.8%, being the highest for first and second-generation cephalosporins and 0%
      for third generation cephalosporins. The frequency of immediate allergic
      reactions to cephalosporins is considerably lower compared to penicillins, and
      the degree of cross-reactivity between cephalosporins and penicillins depends on
      the generation of cephalosporins, being higher with earlier generation
      cephalosporins. The cross-reactivity among cephalosporins is lower compared to
      cross-reactivity between penicillins and cephalosporins.

PMID- 15943599
TI  - Aerosol delivery to young children by pMDI-spacer: is facemask design important?
AB  - This study aimed at identifying in a daily-life setting the influence of facemask
      design on drug delivery via a spacer to young children. In a 4-week randomized
      crossover study, 24 children (7-23-months old) with recurrent wheeze tested the
      AstraZeneca, Galemed, and Hans Rudolph facemask combined with the NebuChamber at
      home. Each mask was tested twice daily for seven consecutive days. Filters
      positioned between the NebuChamber and facemask trapped the budesonide aerosol
      (200 microg, Pulmicort). Parents were asked to score the child's degree of
      cooperation during administration on diary cards. The administration procedure
      was evaluated through video recordings. Mean filter dose (standard deviation
      (s.d.)), expressed as % of nominal dose, was 39% (14), 47% (12), and 42% (11) for
      the AstraZeneca, the Galemed and the Hans Rudolph mask, respectively.
      Irrespective of the degree of cooperation, the Galemed mask gave significantly
      higher mean filter doses than the other masks (level of significance) (p <
      0.045). Median (range) within-subject dose variability, expressed, as coefficient
      of variation (CV), was 37% (19-255), 32% (9-114), and 30% (9-115) for the
      AstraZeneca mask, the Galemed mask and the Hans Rudolph mask, respectively, not
      significant. Dose variability increased with decreasing cooperation for all three
      masks (p = 0.007). Drug delivery to young children with recurrent wheeze by means
      of the NebuChamber can be enhanced using the Galemed facemask. Dose variability
      seems to be independent of facemask design but mainly depends on cooperation.

PMID- 15943600
TI  - Fetal growth promotion in allergic children.
AB  - Several in vitro studies have suggested the presence of Th2-skewed immunity
      during pregnancy in infants with atopic diseases. Our study indicated that
      allergic infants showed a higher birth weight and shorter gestational period at
      birth than those of non-allergic peers. Moreover, allergic mothers gave birth to
      neonates whose birth weights and gestational ages were higher and shorter than
      those of the non-allergic mothers, respectively. Thus, our data clearly
      demonstrated the promotion of intrauterine growth, either in the allergic
      children, or allergic mothers. Such an intrauterine environment favorable for the
      fetal growth may also accelerate the development of allergic diseases in their
      offspring that are most probably caused by the Th2-oriented immunity.

PMID- 15943601
TI  - A common variable immunodeficient patient who developed acute disseminated
      encephalomyelitis followed by the Lennox-Gastaut syndrome.
AB  - Common variable immunodeficiency (CVID) is a primary disorder characterized by
      impaired antibody production. CVID patients may develop recurrent infections,
      autoimmune disorders, and malignant lymphomas, but to our knowledge, there is no
      report on CVID patients who develop acute disseminated encephalomyelitis (ADEM)
      or the Lennox-Gastaut syndrome. We describe a 1-yr-old female CVID patient with
      ADEM who evolutionally manifested the Lennox-Gastaut syndrome. She was admitted
      with convulsions and T2-weighted magnetic resonance imaging (MRI) revealed high
      intensity areas in the right temporal lobe and the left fronto-parietal region
      but she became conscious soon. Her serum findings showed severe
      hypogammaglobulinemia and a follow up MRI revealed that these areas had
      diminished. Consequently, she was diagnosed as having CVID with ADEM. After 5
      months, she fell to having tonic and absence seizures and we diagnosed her as
      having the Lennox-Gastaut syndrome from electroencephalograms (EEG) and the
      seizure pattern. She is now 7 yr old and her tonic seizures are controlled with
      valproic acid, clobazam, and immunoglobulin replacement therapy which is
      administrated every 2 wk. It is well known that the immune and neurologic systems
      have a close relationship. We suspect that a genetic defect in the immune system
      of our patient might also be associated with the neurologic disorders of ADEM and
      the Lennox-Gastaut syndrome.

PMID- 15943602
TI  - Anaphylaxis to povidone in a child.
AB  - Povidone is an allergic agent present in numerous substances, food and medicines.
      The authors present the clinical case of a 9-yr-old male child admitted in the
      emergency room with anaphylaxis, in two occasions separated by a 6-month period.
      The first episode occurred 5 min after the first oral administration of Fluvermal
      (flubendazole) and the second occurred 10 min after cutaneous application of
      Betadine (povidone iodine solution). Previous cutaneous application of this
      solution and ingestion of mebendazole occurred without apparent adverse
      reactions. The allergy study revealed eosinophilia, an elevated total IgE level
      and positive prick-by-prick test for both drugs. A cutaneous prick-by-prick test
      with povidone (the sole common constituent) was also positive. This is probably
      the first case described in the literature of anaphylaxis induced by povidone in
      a child.

PMID- 15943603
TI  - Dose-dependent effects of resistant potato starch in the diet on intestinal
      skatole formation and adipose tissue accumulation in the pig.
AB  - Resistant starch (RS) intake leads to a reduction of apoptosis in the pig colon
      and thus to a reduction of skatole in the carcass. To determine the minimal
      amount of RS which is required for the effect, diets with varying amounts (20, 30
      and 40%) of RS were fed to barrows and gilts. Controls were fed instead with 55%
      pre-gelatinized starch. Skatole was determined after slaughter in distal colon
      content and in adipose tissue (flare fat and belly fat). Resistant starch led to
      a dose-dependent reduction of skatole in the gut content from 134 microg/g dry
      matter (controls) to 4.8 microg/g in the 40% group. Flare fat concentrations were
      decreased from 159 to 20 ng/g fat and belly fat concentrations from 64 to 16 ng/g
      fat. Strategies to improve sensorial quality by feeding RS continuously or for
      only 1 week prior to slaughter are discussed.

PMID- 15943604
TI  - Alpha-1-acid glycoprotein inhibits phorbol ester-induced but not Fc-receptor
      induced generation of reactive oxygen species in bovine peripheral blood
      neutrophils.
AB  - Alpha-1-acid glycoprotein (AGP) is an acute-phase protein with anti-inflammatory
      and immunomodulating properties. AGP is described as a potent inhibitor of the
      production of reactive oxygen species (ROS) in human neutrophils. However,
      published reports about the mechanism of inhibition are conflicting. The
      influence of bovine AGP on the production of ROS by bovine peripheral blood
      polymorphonuclear leucocytes (PMN) was studied using a highly sensitive method
      approaching its inhibitory mechanism. ROS production in PMN was induced with
      phorbol 12-myristate 13-acetate (PMA) or opsonized Staphylococcus aureus
      bacteria. ROS generation was quantified and evaluated by flow cytometry. AGP
      efficiently suppressed PMA, but did not opsonize bacteria-induced ROS generation
      in vitro. The suppressive effect was concentration-dependent and adversely
      proportional to PMA concentration. The selective inhibitory potential of AGP in
      comparison with ovalbumin (OVA) and bovine serum albumin (BSA) showed that ROS
      inhibition was not a mere protein effect. ROS production was suppressed only if
      AGP and PMA were simultaneously present with PMN. Pre-incubation of PMN with AGP
      did not alter the PMN response to PMA. Moreover, AGP could not suppress ROS
      production after pre-stimulation of PMN with PMA. Human and bovine AGP did not
      differ in their inhibitory potential to the PMA-induced ROS production in bovine,
      human and equine PMN. The results show that AGP does not modulate bovine
      neutrophil functions directly, but acts as a scavenger of PMA.

PMID- 15943605
TI  - The Influence of long-chain polyunsaturated fatty acids on total lipid fatty acid
      composition of a canine mastocytoma cell line.
AB  - Cutaneous mast cells are considered as key immune effectors in the pathogenesis
      of canine atopic dermatitis (CAD). These cells release immediate-phase and late
      phase mediators of inflammation. Dietary fatty acids are incorporated in cellular
      membranes and seem to influence mediator production and release. A dietary
      intervention with n6- and n3-fatty acids is thought to alleviate clinical
      symptoms in atopic dogs. The purpose of this study was to examine the effects of
      n6- and n3-fatty acids on the fatty acid composition of canine mastocytoma cells
      (C2) as a possible model for CAD. The C2 was cultured in a basic medium called
      Dulbecco's modified Eagle's medium (DEH) or with additional 14 mum linoleate
      (C18:2n6, DEH-LA), gamma-linolenate (C18:3n6, DEH-GLA), arachidonate (C20:4n6,
      DEH-AA), alpha-linolenate (C18:3n3, DEH-LnA), eicosapentaenoate (C20:5n3, DEH
      EPA) or docosahexaenoate (C22:6n3, DEH-DHA). Cell growth was examined for 11 days
      in all media. Cell growth increased from days 1 to 8 and decreased thereafter in
      all media conditions. The fatty acids supplied did not influence cell growth. The
      cells were harvested after 8 days for fatty acid analysis. The fatty acid
      composition was determined by gas chromatography after extraction and trans
      esterification of the lipids. The added fatty acids increased the concentration
      of these fatty acids in C2 differently (LA 4.9-fold, GLA 6.9-fold, AA 6-fold, LNA
      9.3-fold, EPA 6.5-fold and DHA 8.4-fold). Furthermore, elongated and Delta6
      desaturated products of the corresponding fatty acids were significantly
      elevated. However, Delta5-desaturated products were not measurable. These results
      let us assume that C2 has no measurable activity of the Delta5-desaturase. In
      case the low activity of Delta5-desaturase is one of the mechanisms underlying
      the pathogenesis of CAD, C2 seems to be an adequate model for investigations in
      CAD.

PMID- 15943606
TI  - Giant cell tumour of bone in a cat with extraskeletal metastases: pathological
      and immunohistochemical study.
AB  - A case of giant cell tumour of bone (GCTb) in the lung and in a subcutaneous mass
      located in the right flank, with a probable primary origin in the mid-diaphysis
      of the right tibia, was described in a 8-year-old female cat. Numerous
      multinucleated giant cells were homogeneously distributed among a population of
      ovoid or spindle-shaped mononuclear cells. All of them were positive for vimentin
      suggesting a mesenchymal origin. Spindle-shaped tumour cells resemble
      fibroblastic cells, showing collagen fibres in their vicinity. Ovoid mononuclear
      cells are similar to macrophages, with a cytoplasm rich in electron-dense
      lysosomes. Multinucleated giant cells appear morphologically similar to
      osteoclasts. These findings are supported for the positive reaction to tartrate
      resistant acid phosphatase (TRAP) and lysozyme, encountered only in ovoid and
      multinucleated giant cells. No immunoreactivity against human oestrogen receptors
      was observed in the nuclei of any neoplastic cells.

PMID- 15943607
TI  - Mitochondrial damage as an early event of monensin-induced cell injury in
      cultured fibroblasts L929.
AB  - The present study was designed to identify, submicroscopically, the primary
      organelle or target structure for monensin in cultured murine fibroblasts L929.
      In addition, the effect of the drug on cell size and surface membranes of the
      cells were analysed; cellular proliferation, collagen secretion, and necrosis and
      apoptosis were re-evaluated. At the lowest concentration of monensin the foremost
      ultrastructural alteration occurred in the mitochondria, characterized by
      increased matrix density with disorganized and less distinct crystae. Incubation
      with monensin at higher concentrations resulted in severe mitochondrial damage
      and marked dilatation of the Golgi apparatus and rough endoplasmic reticulum
      cisternae. Fibroblasts exposed to higher concentrations of monensin were enlarged
      with decreased number of filopodia and hollows in the surface membrane. Moreover,
      monensin inhibited the cell proliferation, increased immunohistochemical
      positiveness for collagen type I in a dose-dependent manner, and, at high
      concentrations, caused cell necrosis whereas apoptosis was not induced. Taken
      together, these results show that monensin induces early mitochondrial damage,
      possibly causing an energy deficit that led to inhibition of fibroblasts
      proliferation and accumulation of collagen causing dilatation of Golgi apparatus
      and rough endoplasmic reticulum. Moreover, the mitochondrial damage would also
      explain the monensin-induced necrosis.

PMID- 15943608
TI  - Effect of orally administered omeprazole on abomasal luminal pH in dairy calves
      fed milk replacer.
AB  - The objective of this study was to determine whether oral administration of
      omeprazole, a proton-pump inhibitor, increased abomasal luminal pH in calves fed
      milk replacer. Four male dairy calves with cannulae in the abomasal body suckled
      milk replacer (60 ml/kg body weight every 12 h) and were administered a non
      enteric-coated omeprazole (4 mg/kg body weight every 24 h) in a paste formulation
      for five successive days. Abomasal luminal pH was continuously measured using
      miniature glass pH electrodes. On the first day of omeprazole administration,
      there was a significant (P<0.05) increase in mean 24-h pH from 2.89 to 4.17. The
      mean 24-h pH on days 2, 3, 4 and 5 of omeprazole administration were 3.85, 4.02,
      3.97 and 3.39 respectively. We conclude that oral administration of non-enteric
      coated omeprazole increased abomasal luminal pH in calves fed milk replacer, but
      that the effect may decrease over time.

PMID- 15943609
TI  - Ultrasonic assessment of puerperal uterine involution in Balady goats.
AB  - Twenty-six postpartum Balady goats (primiparous, n=13; pluriparous, n=13) were
      used in this study. One animal of each group was slaughtered on postpartum days
      1, 2, 4, 7, 10, 13, 19 and 25; in addition, three control nulliparous goats were
      slaughtered, and the genital tracts collected. Progress of uterine involution was
      monitored by repeated ultrasonographic measurements in live animals (primiparous
      n=6; pluriparous n=6) and measurement of the outer circumference of the uterine
      horns of slaughtered animals (primiparous n=8; pluriparous n=8). A consistent and
      progressive decrease in ultrasonographic and outer circumference measurements was
      found, although faster during the first 7 days postpartum than between days 7 and
      19 postpartum. Uterine involution, assessed by the upper limit of the
      measurements in the nulliparous goats, followed a quadratic pattern and was
      completed by day 19 postpartum. Ultrasonographically, two elliptical-circular
      echogenic areas separated by an anechoic line of the stratum vascularis were
      depicted. Regressing caruncles and fluid in uterine lumen were recognized during
      the first week postpartum. Further analysis revealed a highly positive
      correlation between the outer circumference and ultrasonographic measurements. In
      conclusion, uterine involution in Balady goats was completed by day 19 postpartum
      and was unrelated to parity. The close association between ultrasound findings
      and macroscopic involution indicated that ultrasonography can dependably be used
      to monitor uterine involution under field conditions and can be a suitable
      alternative to animal slaughter for the study of uterine involution.

PMID- 15943610
TI  - Is metoclopramide an alternative to tramadol in management of post-operative
      pain? An experimental study.
AB  - In this study, metoclopramide was compared with other pharmacological agents for
      preventing post-operative pain. Sixty Sprague-Dawley male rats, weighing 310-345
      g were included in the study; 1 cm surgical incision, including skin, facia, and
      muscle was made to the plantar surface of rear foot of all anaesthetized rats.
      Rats were randomized into four groups. In group 1 (group S) 2 cm3 saline, in
      group 2 (group M) 2 cm3 metoclopramide (5 mg/kg) in group 3 (group T) 2 cm3
      tramadol (45 mg/kg), in group 4 (group M+T) half doses of group M and group T was
      given intraperitoneally. Post-operative pain was assessed after 2 h, first and
      second days of incision. Post-operative pain scores were found to be
      significantly lower in group M, group T and group M+T when compared with the
      control group. But there was no significant difference between these groups. We
      concluded that metoclopramide, with low cost, fewer side-effects and being
      significantly effective for preventing post-operative pain, can be an alternative
      to tramadol.

PMID- 15943611
TI  - Genetic evaluation of elbow angles as predictors of elbow dysplasia in German
      shepherd dogs.
AB  - Elbow angles were measured in X-rays of both elbows to elucidate the usefulness
      of such data for selecting against elbow dysplasia (ED) in German shepherd dogs.
      These measurements record the size, proportions and alignments of the anconeal
      process (PA), the radius (RA), the olecranon (OL), and the ulnar trochlear notch
      (UL). The reference system for evaluating the information content of the
      measurements was the score for ED (ED-SV) as recommended by the International
      Elbow Working Group. Data from 2645 X-rayed dogs born from 1998 to 2001 in 1331
      kennels were analysed by using residual maximum likelihood procedures to estimate
      heritabilities, additive genetic correlations and residual correlations. The
      pedigree file included 11,426 dogs and contained ancestors for up to six
      generations. ED-SV was significantly influenced by sex, by age within sex and by
      month of birth. The elbow angles were significantly influenced by the month and
      year of birth, X-ray positioning of the dog's forelimbs, angle of elbow flection,
      litter size and number of dogs X-rayed by the veterinary practitioners. The
      following heritability estimates were found: h2=0.18+/-0.04 for ED; h2=0.76+/
      0.04 for OL; h2=0.52+/-0.05 for PA; h2=0.50+/-0.04 for UL; and h2=0.39+/-0.04 for
      RA. The additive genetic correlations of ED-SV with three elbow angles (OL, UL
      and RA) were close to zero. A higher additive genetic correlation to ED-SV was
      found only for PA, for which r(g)=0.31. The distributions of predicted breeding
      values for susceptibility to ED were not affected by regarding the elbow angles
      as additional traits in the multivariate prediction procedure. Measurements of
      elbow angles were thus shown to be unsuitable for use in selection programmes
      against ED in German shepherd dogs.

PMID- 15943613
TI  - Split liver sharing in the United States.

PMID- 15943614
TI  - Autologous stem cell and kidney transplantation for primary amyloidosis
      associated with ESRD: which should come first?

PMID- 15943615
TI  - Is it right to promote living donor liver transplantation for fulminant hepatic
      failure in pediatric recipients?
AB  - Good clinical results are currently achieved in elective pediatric liver
      transplantation (LT) with living-related donors. However, the question whether
      such therapeutic approach may also be promoted in case of fulminant hepatic
      failure (FHF) remains a matter of debate. This work briefly reviews the ethical
      background and overall medical results of living-related donation in pediatric
      LT. When considering FHF, success is essentially conditioned by the availability
      of a suitable organ donor before the onset of irreversible brain damage and death
      of the transplant candidate on the waiting list. Accordingly, living donor LT
      provides several advantages for patients with FHF, including the short waiting
      time and the access to a transplant with reduced ischemic injury and optimal
      graft quality; however, living donation is also characterized by several
      drawbacks to be carefully considered, particularly the possibility of coercion to
      the recipient's family as well as the operative risks of the emergency donor
      hepatectomy. The ethical soundness of living parental donor LT for FHF is
      discussed, with emphasis to the type of medical context, with or without access
      to an efficient emergency postmortem organ sharing system.

PMID- 15943616
TI  - Reproduction and transplantation: report on the AST Consensus Conference on
      Reproductive Issues and Transplantation.
AB  - It has been almost 50 years since the first child was born to a female transplant
      recipient. Since that time pregnancy has become common after transplantation, but
      physicians have been left to rely on case reports, small series and data from
      voluntary registries to guide the care of their patients. Many uncertainties
      exist including the risks that pregnancy presents to the graft, the patient
      herself, and the long-term risks to the fetus. It is also unclear how to best
      modify immunosuppressive agents or treat rejection during pregnancy, especially
      in light of newer agents available where pregnancy safety has not been
      established. To begin to address uncertainties and define clinical practice
      guidelines for the transplant physician and obstetrical caregivers, a consensus
      conference was held in Bethesda, Md. The conferees summarized both what is known
      and important gaps in our knowledge. They also identified key areas of agreement,
      and posed a number of critical questions, the resolution of which is necessary in
      order to establish evidence-based guidelines. The manuscript summarizes the
      deliberations and conclusions of the conference as well as specific
      recommendations based on current knowledge in the field.

PMID- 15943617
TI  - Workshop on late renal allograft dysfunction.
AB  - Despite continued improvement in incidence of acute immune injury and short-term
      graft survival, late allograft dysfunction remains a significant problem in the
      renal transplant population. Recent reports suggest that rates of renal function
      decline are quite varied in the overall recipient population, and that individual
      rates for many recipients may not change substantially over time. Moreover,
      analyses also reveal distinct predictive factors for both early and late
      functional decline. Long-term outcome studies for renal transplantation, however,
      might be significantly limited by incomplete data sets for assessing clinical
      endpoints. In view of the heterogeneous factors that may cause progressive
      allograft injury, more routine biopsy sampling would allow a more complete
      characterization of induced injuries. Elucidating mechanisms of renal fibrosis in
      response to injury, in experimental systems and humans, is also an important goal
      in better understanding chronic allograft damage. Regulation of cell senescence
      genes and epithelial to mesenchymal transition, studied in other models of renal
      fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent
      technical advances in analyzing biological samples may play a pivotal role in
      identifying and validating surrogate markers of allograft function for future
      interventional trials in transplantation.

PMID- 15943618
TI  - Renal ischemia/reperfusion injury activates the enhancer domain of the human
      cytomegalovirus major immediate early promoter.
AB  - Reactivation of latent human cytomegalovirus is of significant concern in
      immunocompromised transplant patients and is likely to occur through
      transcriptional activation of immediate early (ie) gene expression through
      mechanisms that are not well understood. TNF-mediated activation of NF-kappaB has
      been proposed to be one pathway leading to transcriptional activation of CMV ie
      gene expression. Using transgenic mice carrying a lacZ reporter gene under the
      control of the HCMV major ie promoter/enhancer (MIEP-lacZ mice) and MIEP-lacZ
      mice deficient in TNF receptor 1 and TNF receptor 2 (MIEP-lac Z TNFR DKO mice),
      we demonstrate that renal ischemia/reperfusion (I/R) injury activates the HCMV
      enhancer independently of TNF. Induction of MIEP-lacZ expression was preceded by
      TNFR-independent formation of reactive oxygen species (ROS), weak and transient
      activation of NF-kappaB and strong and sustained activation of AP-1. Our studies
      show that, in addition to TNF-mediated signaling, TNF-independent signaling
      induced by I/R injury can contribute to the activation of the HCMV enhancer. This
      likely occurs through ROS-mediated activation of AP-1. Targeting MAP kinase
      signaling pathways as well as NF-kappaB may be of therapeutic value in patients
      with CMV infection.

PMID- 15943619
TI  - Acquisition of HLA-DR and costimulatory molecules by T cells from allogeneic
      antigen presenting cells.
AB  - There is accumulating evidence that cell surface molecules may be transferred
      between cells during an encounter. The aim of these experiments was to determine
      whether transfer of allogeneic material to T cells could influence human
      alloresponses. CD4(+) cells were cocultured with M1 cell (human fibroblast)
      transfectants expressing HLA-DR1, CD80 and CD86 alone or in combination. Up to
      95% of the allogeneic T cells became positive for HLA-DR and the appropriate
      costimulatory molecules after only 4 h of coculture. The phenomenon required cell
      contact and cell membrane fluidity because transfer was abolished by transwell
      separation of the M1 cells and the T cells or by pre-treatment of the APC with
      paraformaldehyde. Flow cytometric sorting of T cells after coculture and
      subsequent mixed lymphocyte assays demonstrated that the T cells that had
      acquired both HLA-DR and costimulatory molecules could act as potent antigen
      presenting cells. Finally, matured human dendritic cells were also shown to
      transfer these molecules to CD4(+) cells, which could then act as antigen
      presenting cells for unprimed T cells and for a cell line specific for an HLA
      peptide complex acquired from the DCs. Taken together, these data suggest a novel
      pathway for the amplification of human alloresponses.

PMID- 15943620
TI  - Indirect recognition of MHC class I allopeptides accelerates lung allograft
      rejection in miniature swine.
AB  - The role of indirect allorecognition in graft rejection is examined in two
      experiments using a swine lung transplantation model. First, two swine received
      class I mismatched grafts without immunosuppression; another two recipients were
      treated postoperatively with cyclosporine (CsA). These swine exhibited acute and
      chronic rejection, respectively. All four recipients developed T-cell reactivity
      to donor-derived class I major histocompatibility complex (MHC) peptides. Second,
      six swine were immunized with synthetic donor-derived class I allopeptides prior
      to transplantation. Control groups consisted of nonimmunized recipients (n = 6)
      and recipients immunized with an irrelevant peptide (n = 3). These recipients all
      received a 12-day course of post-operative CsA. Swine immunized with allopeptides
      exhibited accelerated graft rejection, as compared to both control groups (p <
      0.01 and p = 0.03, respectively). Within the experimental group, the dominant
      histologic finding was acute rejection (AR). Obliterative bronchiolitis (OB) was
      seen in the graft with the longest survival. Both control groups showed a lesser
      degree of AR, with four out of six nonimmunized swine ultimately developing OB.
      These studies suggest that indirect allorecognition is operative during lung
      allograft rejection, and that pre-transplant sensitization to donor-derived MHC
      allopeptides can accelerate graft rejection.

PMID- 15943621
TI  - A novel method for the assessment of cellular composition and beta-cell viability
      in human islet preparations.
AB  - Current methodologies to evaluate islet cell viability are largely based on tests
      that assess the exclusion of DNA-binding dyes. While these tests identify cells
      that have lost selective membrane permeability, they do not allow us to recognize
      apoptotic cells, which do not yet stain with DNA-binding dyes. Furthermore,
      current methods of analysis do not discriminate between cell subsets in the
      preparation and, in particular, they do not allow for selectively defining beta
      cell viability. For these reasons we have developed novel methods for the
      specific assessment of beta-cell content and viability in human islets based on
      cellular composition analysis through laser scanning cytometry (LSC) coupled with
      identification of beta-cell-specific apoptosis at the mitochondrial level. Our
      novel analytical methods hold promise to prospectively analyze clinical islet
      transplantation preparations and predict functional performance, as suggested by
      the observed correlation with in vivo analysis of islet potency in
      immunodeficient rodents.

PMID- 15943622
TI  - Split-liver transplantation using the left lateral segment: a collaborative
      sharing experience between two distant centers.
AB  - Split-liver transplantation (SLT) increases the pool of organs for pediatric
      orthotopic liver transplantation (pOLT). With increased collaboration and organ
      sharing, transplant centers can fully maximize the use of all split donor
      allografts. Herein, we report the collaborative results between two distant
      centers involved in a sharing alliance. The current study consists of a
      retrospective review of 56 pediatric LLS transplants performed at two
      collaborating centers between 9/1997 and 10/2003. Fifty-three patients (41%
      Status 1) were transplanted using 56 left lateral segment (LLS) grafts. Sixteen
      percent of LLS grafts were shared between the two institutions. Overall patient
      survival at both 1 and 3 years was 90% and 90%, respectively. Overall graft
      survival at both 1 and 3 years was 82% and 82%, respectively. Shared patient and
      graft survival was 89% and 89%, respectively. There was an 11% biliary
      complication and 18% vascular complication rate. Five patients required
      retransplantation. In conclusion, SLT increases the number of available
      allografts for pOLT. While SLT is technically demanding, with a significant
      learning curve, patient and graft survival rates compare favorably with United
      Network Organ Sharing (UNOS) averages. Sharing of grafts between centers is a
      safe and effective way to maximize organ usage and should be actively pursued
      through collaborative networks.

PMID- 15943623
TI  - Split-liver transplantation: results of statewide usage of the right trisegmental
      graft.
AB  - Split-liver transplantation (SLT) effectively expands the cadaveric donor pool
      for children. The remaining right trisegmental (RTS) graft can be transplanted
      into adults. Limited information exists regarding the outcomes of RTS allografts.
      Sixty-five RTS graft recipients from five adult transplant programs in Texas were
      identified. Donor and recipient information were analyzed retrospectively. Most
      livers (75%) were originally allocated to pediatric recipients. Liver splitting
      occurred via the in situ (72%) and ex situ (28%) techniques. Arterial
      reconstruction of RTS grafts was common (52%). Patient and graft survival at 3
      months were comparable for the in situ and ex situ techniques (p = 0.2). Cox
      regression showed only in situ splitting to be a predictor of outcome longer than
      3 months posttransplant. Sharing of grafts between centers was frequent (37% of
      total). One-year patient and allograft survival (87.1% and 85.4%) were excellent
      with no cases of primary nonfunction. SLT consistently generates two functional
      liver allografts with excellent recipient survival. In situ splitting of the
      liver is the preferred technique. Decreased survival is observed with RTS graft
      use in higher risk recipients. Broader application of SLT with increased sharing
      is feasible and safely expands the number of liver allografts that can be
      transplanted.

PMID- 15943624
TI  - Living donor kidney and autologous stem cell transplantation for primary systemic
      amyloidosis (AL) with predominant renal involvement.
AB  - Primary systemic amyloidosis (AL) is characterized by multiorgan deposition of
      monoclonal immunoglobulin light chain. Renal involvement is common and impaired
      kidney function is associated with reduced median survival. Autologous stem cell
      transplantation (SCT) for AL achieves superior response rates compared to
      chemotherapy alone but patients with end-stage renal disease (ESRD) may be
      excluded from consideration. A treatment approach consisting of living donor
      kidney transplantation (LDKTx) followed by autologous SCT was developed for AL
      with ESRD. Eight patients underwent LDKTx with immediate graft function. Two
      suffered unanticipated complications post-KTx and died 10 and 3 months later. Two
      cases of subclinical acute cellular rejection (ACR) and one case of clinical ACR
      occurred--all reversible with corticosteroid. Six patients had successful stem
      cell harvests performed and five of these underwent SCT with satisfactory
      trilineage engraftment. Renal function remained stable following SCT in four and
      was reduced in one due to infectious and bleeding complications. One patient, who
      has thus far elected not to undergo SCT, has proteinuria and histologic evidence
      of recurrent renal amyloidosis. This experience supports the feasibility of
      sequential living donor KTx and autologous SCT for carefully selected patients
      with ESRD due to AL.

PMID- 15943625
TI  - Attitudes, psychology, and risk taking of potential live kidney donors:
      strangers, relatives, and the general public.
AB  - It is unclear whether potential living kidney donors and the general public
      differ in attitudes and psychological characteristics. We performed a case
      control study to explore differences in these groups using a standardized
      questionnaire (analyzed using conditional logistic regression). Strangers (N =
      42) were more willing than controls (N = 126) to incur risks: 64% strangers
      versus 35% controls accepting >50% medical complications (MC) risk; 90% strangers
      versus 61% controls accepting >8 days hospitalization; 71% strangers versus 43%
      controls accepting >3 months unpaid; 55% strangers versus 16% controls accepting
      100% kidney failure (KF) risk; 70% strangers versus 34% controls accepting < or
      =10% likelihood of successful transplant (all p < 0.01). Relatives (N = 251) were
      also more willing than controls (N = 251) to incur risks. Strangers were most
      willing to incur MC, KF and transplant failure. Groups did not differ in
      attitudes, depression or anxiety. Potential stranger and related donors are
      willing to undergo greater risks with donation than the general public, but do
      not differ in other attitudes, depression or anxiety. This should help reassure
      transplant centers and the public that both forms of live donation do not
      necessarily involve increased ethical risks of donor coercion or irrational
      thought processes. Still, careful attention to communication of all risks of
      donation is warranted.

PMID- 15943626
TI  - Are we frozen in time? Analysis of the utilization and efficacy of pulsatile
      perfusion in renal transplantation.
AB  - Preservation techniques are crucial to deceased donor kidney transplantation
      (DDTx), but the efficacy of pulsatile perfusion (PP) versus cold storage (CS)
      remains uncertain. We describe patterns of PP use and explore four fundamental
      questions. What kidneys are selected for PP? How does PP affect utilization of
      donated kidneys? What effect does PP have on outcomes? When does PP appear to be
      most efficacious? We examined rates of PP in DDTx in the United States from 1994
      to 2003. We generated models for organ utilization, delayed graft function (DGF)
      and for the use of PP. We analyzed the long-term effect of PP with multivariate
      Cox models. The utilization rates for non-expanded criteria donors (ECDs) were
      similar by storage type, but for ECDs there was a significantly higher
      utilization rate with PP (70% with PP vs. 59% with CS, p < 0.001). Use of PP was
      widely variable across transplant centers. DGF rates were significantly lower
      with PP (27.6% vs. 19.6%). PP was associated with a mild benefit on death
      censored graft survival (adjusted hazard ratio = 0.88, 95% CI 0.85-0.91). Reduced
      DGF and significantly lower discard rates of ECDs associated with PP suggest an
      important utility of PP in renal transplantation. Additional evidence of
      improvement in graft survival, particularly in more recent years, provides
      further encouraging evidence for the use of PP.

PMID- 15943627
TI  - Early subclinical coronary artery calcification in young adults who were
      pediatric kidney transplant recipients.
AB  - Coronary artery disease (CAD) is the leading cause of death in adults after
      successful kidney transplantation. Children who have undergone successful kidney
      transplantation are entering young adulthood; however, the prevalence and extent
      of CAD in this population is unknown. We conducted a pilot study in young adults
      with stable allograft function, who received kidney transplants as children to
      measure coronary artery calcification (CAC), a marker of coronary artery
      atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric
      kidney transplantation for known CAD risk factors; these patients underwent
      noninvasive imaging with electron-beam computed tomography (EBCT) for measurement
      of CAC. Prevalence and quantity of CAC were then compared to asymptomatic
      individuals from the community. All patients had multiple risk factors for CAD.
      Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in
      individuals in the community in this age range; however, nearly half of our
      patients had CAC detected with the quantity of CAC comparable to asymptomatic
      individuals from the community 10-40 years older. These data suggest young adults
      who received pediatric kidney transplants are at increased risk for developing
      early CAC and need close monitoring to detect early CAD so as to prevent
      premature cardiac morbidity and mortality.

PMID- 15943628
TI  - Tailoring the type of donor hepatectomy for adult living donor liver
      transplantation.
AB  - Donor hepatectomies for adult living donor liver transplantations were performed
      in 200 consecutive donors to harvest a left liver (LL) graft (n = 5), a LL plus
      caudate lobe (LL + CL) graft (n = 63), a right liver (RL) graft (n = 86), a RL
      and middle hepatic vein (RL + MHV) graft (n = 28) or a right lateral sector (RLS)
      graft (n = 18). The graft type was selected so that at least 40% of the
      recipient's standard liver volume was harvested. No donor deaths occurred, and no
      significant differences in the morbidity rates among either donors or recipients
      were observed when the outcomes were stratified according to the graft type.
      Donors who donated RL exhibited higher values of serum total bilirubin and
      prothrombin time than those who donated non-RL (LL, LL + CL, RLS) grafts. The
      time taken for hilar dissection and parenchymal transection increased in the
      following order: RLS graft, LL graft and RL graft harvesting. In conclusion, non
      RL grafting was more time consuming, but the hepatic functional loss in the
      donors was smaller. Our graft selection criteria were useful for reducing the use
      of RL grafts with acceptable morbidity in both donors and recipients.

PMID- 15943629
TI  - Natural history of hepatitis C virus-related liver fibrosis after renal
      transplantation.
AB  - The aim of our study was to assess hepatitis C virus (HCV) evolution and long
      term liver histology outcome in anti-HCV(+)/RNA(+) renal transplant (RT)
      patients. A total of 51 anti-HCV(+)/RNA(+) RT patients underwent liver biopsies
      (LB) every 3-4 years after transplantation (two LBs, n = 51; three LBs, n = 42;
      four LBs, n = 9). The hypervariable region (HVR)-1 of the HCV genome from all
      patients was characterized over time. Overall, the rate of liver fibrosis
      progression was 0.09 +/- 0.03 Metavir units/year. We identified three groups of
      patients: those in whom liver fibrosis remained stable (n = 21), those with
      progressing liver fibrosis (n = 21) and those with a regression in liver fibrosis
      (n = 10). In the last two groups, the progression and the regression of liver
      fibrosis were gradual during follow-up. Ferritin levels and hepatosiderosis were
      significantly higher in fibrosers. Initial fibrosis stage and high
      diversification of the HVR-1 of HCV genome between transplantation and the first
      liver biopsy were independent factors associated with liver fibrosis regression.
      In conclusion, in the current study, more than 10 years after renal
      transplantation, HCV infection was not harmful upon liver histology in more than
      50% of patients. The diversification of the HVR-1 might be used to predict liver
      fibrosis outcome.

PMID- 15943630
TI  - Increasing incidence of post-kidney transplant anemia in children.
AB  - Anemia status at 1-year post-kidney transplant was documented retrospectively in
      231 pediatric recipients (mean age: 12.6 +/- 5.0, range: 1.9-20.7 years) at
      Cincinnati Children's Hospital Medical Center between 1978 and 2003. Anemia was
      present in 59 (25.5%) patients. The prevalence of anemia has increased in the
      more recent eras (1978-1985: 7.8%, 1986-1997: 29%; 1998-2003: 32%, p < 0.01).
      Logistic regression analysis determined that the use of calcineurin inhibitors or
      impaired allograft function predicted anemia at 1-year post-transplant. Kaplan
      Meier analysis showed that children with anemia at 1-year post-transplant had a
      significantly worse overall allograft survival than children without anemia (p =
      0.02). However, when data were analyzed using a Cox proportional hazards model,
      only lower allograft function at 1-year post-transplant, black race and older
      era, but not anemia, independently predicted worse graft survival in children.
      This study suggests that the recent increase in the incidence of anemia post
      kidney transplant is related to modern immunosuppressive therapy and that post
      transplant anemia is more likely a marker of allograft dysfunction in children
      rather than its cause.

PMID- 15943631
TI  - Patient survival following renal transplant failure in Canada.
AB  - Studies from the United States have shown that renal allograft failure is
      associated with a high mortality rate. The purpose of this study was to determine
      whether transplant failure was associated with survival in a recent cohort of
      kidney transplant recipients with different characteristics and a distinct health
      care system from the United States. Cox regression was used to model allograft
      loss as a time-dependent variable with patient survival as the primary outcome in
      4743 kidney transplant recipients from the Canadian Organ Replacement Register.
      During follow-up 607 (12.8%) patients had allograft failure and 411 (8.7%) died.
      Patients with a functioning transplant had an unadjusted death rate of 2.06 per
      100 patient years that increased to 5.14 per 100 patient years following
      allograft failure. After controlling for important confounding variables,
      allograft failure was found to increase the risk of death by over threefold
      compared to patients who maintained transplant function (adjusted hazard ratio,
      3.39; 95% CI, 2.75-4.16; p < 0.0001). In conclusion, this analysis has shown that
      kidney transplant failure is an independent predictor of mortality following
      renal transplantation in a Canadian population. This finding supports the premise
      that it is the loss of transplant function, rather than patient or system-related
      issues, that is the main factor contributing to outcome.

PMID- 15943632
TI  - Kidneys from deceased donors: maximizing the value of a scarce resource.
AB  - Donor age is a significant risk factor for graft loss after kidney
      transplantation. We investigated the question whether significant graft years
      were being lost through transplantation of younger donor kidneys into older
      recipients with potentially shorter lifespans than the organs they receive. We
      examined patient and graft survival for deceased donor kidney transplants
      performed in the United States between the years 1990 and 2002 by Kaplan-Meier
      plots. We categorized the distribution of deceased donor kidneys by donor and
      recipient age. Subsequently, we calculated the actual and projected graft
      survival of transplanted kidneys from younger donors with the patient survival of
      transplant recipients of varying ages. Over the study period, 16.4% (9250)
      transplants from donors aged 15-50 were transplanted to recipients over the age
      of 60. At the same time, 73.6% of donors above the age of 50 were allocated to
      recipients under the age of 60. The graft survival of grafts from younger donors
      significantly exceeded the patient survival of recipients over the age of 60. The
      overall projected improvement in graft survival, by excluding transplantation of
      younger kidneys to older recipients, was approximately 3 years per transplant.
      Avoiding the allocation of young donor kidneys to elderly recipients, could have
      significantly increased the overall graft life, by a total 27,500 graft years,
      between 1990 and 2002, with projected cost savings of about 1.5 billion dollars.

PMID- 15943633
TI  - Management of arterial stenosis affecting kidney graft perfusion: a single-centre
      study in 53 patients.
AB  - We assessed clinical and duplex sonographic (CDS) findings, and outcome in
      patients with stenosis of the transplant renal artery (TRAS) or the aorto-iliac
      segment proximal to the graft (Prox-TRAS) treated with dilatation (PTA), stenting
      (PTAS) and surgery. From 1988 to 2002, of 1189 patients with renal
      transplantations, 117 underwent angiography. Fifty-three patients with TRAS (n =
      37)/Prox-TRAS (n = 16) were found (4.4%). Clinical presentation included
      deterioration of hypertension (144 +/- 15/84 +/- 9, 157 +/- 22/90 +/- 10 mmHg; p
      < 0.001), increase of creatinine (1.7 +/- 0.9, 2.5 +/- 1.3 mg/dL; p = 0.01) and
      renal failure (n = 12). CDS indicated insufficient perfusion and differentiated
      between TRAS and Prox-TRAS. From renal transplantation (RTX) until the detection
      of stenosis pulsatility indices (PI) decreased from 1.2 +/- 0.46 to 0.98 +/-
      0.29; (p = 0.001). Fifty-two patients underwent invasive treatment (21 PTA, 10
      PTAS and 21 surgery) after which hypertension and creatinine significantly
      improved. PI increased. Restenosis occurred in 16 (52%) cases of the
      interventional (PTA 62% and PTAS 30%) and in 3 (14%) of the surgical group (p =
      0.011). Hypertension and graft dysfunction due to perfusion problems are rare.
      Clinical findings are nonspecific but CDS findings are helpful to select patients
      for angiography. Invasive treatment leads to clinical improvement. Surgery yields
      better results than PTA, but additional stenting will probably improve the
      outcome of angioplasty.

PMID- 15943634
TI  - Progressive chronic kidney disease after pediatric lung transplantation.
AB  - The development of chronic kidney disease (CKD) was evaluated in a large cohort
      of pediatric lung transplant recipients. Retrospective chart review identified
      125 patients undergoing first lung transplant at St. Louis Children's Hospital
      and surviving 1 year. Mean age at transplant was 10.3 +/- 0.55 years, while mean
      time after transplant was 4.9 years. Serum creatinine nearly doubled from
      baseline 0.48 mg/dL +/- 0.02 (n = 125) to 0.87 mg/dL +/- 0.04 (n = 120) at 1
      year, and tripled to 1.39 mg/dL +/- 0.15 (n = 23) by 7 years after transplant.
      The glomerular filtration rate (GFR), as estimated by the Schwartz formula,
      decreased from baseline 163 +/- 5.9 mL/min/1.73 m(2) (n = 109) to 88 +/- 2.5 (n =
      104), reaching 69 +/- 9.0 (n = 6) by 10 years (p < 0.01). Seven patients
      developed end-stage kidney disease, and by 5 years after transplant, 38% of
      patients reached GFR < 60 mL/min. Older age at transplant and primary diagnosis
      of cystic fibrosis (CF) were both associated with decreased renal survival by
      Kaplan-Meier (KM) analysis. In summary, pediatric lung transplant recipients
      experience significant loss of renal function over time, as observed in other
      solid organ transplant recipients, and is most dramatic in adolescents.

PMID- 15943635
TI  - Calcineurin inhibitor withdrawal from sirolimus-based therapy in kidney
      transplantation: a systematic review of randomized trials.
AB  - Calcineurin inhibitor (CNI) withdrawal has been used as a strategy to improve
      renal allograft function, however, it also carries risk of acute rejection. We
      conducted a systematic review of randomized trials that involved CNI withdrawal
      from a sirolimus-based immunosuppressive regimen. The search strategy yielded six
      trials (n = 1047 patients) reported in eight publications. CNI withdrawal from
      sirolimus-based therapy, was associated with an increased risk of acute rejection
      (risk difference, 6%; 95% CI 2-10%, p = 0.002) but a higher creatinine clearance
      (mean difference, 7.49 mL/min; 95% CI 5.08-9.89 mL/min, p < 0.00001) at 1 year
      compared to continued CNI and sirolimus therapy. Graft loss (relative risk, 0.87;
      95% CI 0.46-1.64, p = 0.66) and death (relative risk, 0.88; CI 0.40-1.96, p =
      0.76) were similar in both groups at 1 year. Hypertension was significantly
      reduced in the CNI withdrawal group (relative risk, 0.56; 95% CI 0.40-0.78, p =
      0.0006). CNI withdrawal from sirolimus-based therapy is associated with an
      increased risk of acute rejection in the short term with a significant
      improvement in renal function and a reduction in hypertension. Longer follow-up
      is needed to determine if these changes will result in a significant improvement
      in patient and graft survival.

PMID- 15943636
TI  - Reversibility of 'secondary hypercalcitoninemia' after kidney transplantation.
AB  - Whether the increase of calcitonin (CT) concentration in patients with chronic
      kidney disease (CKD) is reversible or not after kidney transplantation is not
      known. We examined the effect of kidney transplantation on basal and pentagastrin
      stimulated CT in CKD patients with elevated screening CT levels. Before
      transplantation, the median basal CT concentration of 17 patients was 31 pg/mL
      (13-76), and decreased to 8 pg/mL (4-28) at 23 months (2-34) after kidney
      transplantation (p < 0.00005). The maximum concentration of pentagastrin
      stimulated CT was 63 pg/mL (25-110) before transplantation and decreased to 20
      pg/mL (8-91) (p < 0.00005) thereafter. There was a linear association between CT
      and calcium as well as between phosphorus and parathyroid hormone at the time of
      screening. After transplantation, CT correlated with serum creatinine. Therefore,
      the increase of CT concentration in patients with impaired kidney function
      presumably reflects 'secondary hypercalcitoninemia' due to C-cell hyperactivity.

PMID- 15943637
TI  - CD31+ naive Th cells are stable during six months following kidney
      transplantation: implications for post-transplant thymic function.
AB  - Little is known about thymus function in transplant patients. Until recently, the
      phenotype of T cells that recently emigrated the thymus was unknown. Now it has
      been demonstrated that CD4(+) recent thymus emigrants coexpress CD31 and CD45RA.
      Here, we investigated whether uremia and immunosuppression influence CD31(+)
      CD45RA(+) Th cells before and after kidney transplantation, respectively. Forty
      eight renal transplant patients were included receiving either standard
      triple/quadruple (n = 35) immunosuppression, OKT-3 induction (n = 7) or FTY-720
      (n = 6), respectively. Peripheral CD31(+) CD45RA(+) Th cells were quantified
      flowcytometrically before and at week 1, 4, 12 and 24 post-transplantation.
      Thirty-nine healthy adults served as controls. CD31(+) CD45RA(+) Th cells
      correlated inversely with age in patients and controls and were comparable in
      patients before transplantation and age-matched controls. Importantly, CD31(+)
      CD45RA(+) Th cell frequencies remained stable during 6 months post
      transplantation. In conclusion, CD31(+) CD45RA(+) Th cells are not significantly
      altered by uremia before and during 6 months of immunosuppressive therapy after
      kidney transplantation. Implications for thymus function are discussed.

PMID- 15943638
TI  - Transplantation and 6-month follow-up of renal transplantation from a donor with
      systemic lupus erythematosus and lupus nephritis.
AB  - Transplantation of kidneys with pre-existing glomerulonephritis (GN) has rarely
      been reported. Little is known of the subsequent evolution of donor pathology in
      the recipient. We report a transplant using a donor with systemic lupus
      erythematosus (SLE) and a history of remote acute renal failure but normal renal
      function at death. Although the screening harvest biopsy was unremarkable, time
      zero post-implantation renal biopsy showed evidence of lupus nephritis (LN).
      Sequential protocol biopsies demonstrated gradual resolution of the donor
      pathology, and renal function was stable despite severe cardiac disease in the
      recipient. Studies examining the role of functional and biopsy data on outcomes
      in expanded criteria renal transplantation are reviewed, and the limits of
      guidance from use of this data are discussed. Pre-existing mild GN may not be an
      absolute donor exclusion for candidates willing to accept expanded criteria
      donors. Use of expanded pool kidneys should be guided by functional, biopsy and
      demographic information, as no single factor alone predicts outcome.

PMID- 15943639
TI  - Concurrent verrucous and varicelliform rashes following renal transplantation.
AB  - Verrucous rashes associated with varicella zoster virus (VZV) infection are well
      recognized in HIV infection. Seen rarely in transplant patients, no
      histologically confirmed case has been published in the transplant setting. We
      now report chronic, localized, verrucous VZV in a renal transplant recipient
      presenting with cutaneous dissemination. This case highlights the need to
      consider chronic VZV infection in the differential diagnosis of skin lesions even
      in the VZV seronegative transplant recipient without substantial exposure to
      antiviral agents.

PMID- 15943640
TI  - Treatment of cytomegalovirus infection or disease in solid organ transplant
      recipients with valganciclovir.

PMID- 15943643
TI  - Alcoholics Anonymous: cult or cure?
AB  - OBJECTIVE: To discuss the mechanism of action, the efficacy and the safety of
      Alcoholics Anonymous (AA) in the treatment of alcoholism. METHOD: The published
      works on effective treatments for alcoholism is briefly reviewed and a
      prospective multidisciplinary follow-up of recovery from alcoholism in two
      community cohorts of adolescent males followed from 1940 until the present day is
      reviewed. CONCLUSIONS: The suggested mechanism of action of AA is that it employs
      four factors widely shown to be effective in relapse prevention in addictions:
      external supervision, substitute dependency, new caring relationships and
      increased spirituality. In addition, AA serendipitously follows the principles of
      cognitive behaviour therapy in relapse prevention. Alcoholics Anonymous appears
      equal to or superior to conventional treatments for alcoholism, and the
      skepticism of some professionals regarding AA as a first rank treatment for
      alcoholism would appear to be unwarranted. Alcoholics Anonymous is probably
      without serious side-effects.

PMID- 15943644
TI  - Power Therapies and possible threats to the science of psychology and psychiatry.
AB  - OBJECTIVE: Advocates of new therapies frequently make bold claims regarding
      therapeutic effectiveness, particularly in response to disorders which have been
      traditionally treatment-refractory. This paper reviews a collection of new
      therapies collectively self-termed "The Power Therapies", outlining their
      proposed procedures and the evidence for and against their use. These therapies
      are then put to the test for pseudoscientific practice. METHOD: Therapies were
      included which self-describe themselves as "Power Therapies". Published work
      searches were conducted on each therapy using Medline and PsychInfo databases for
      randomized controlled trials assessing their efficacy, except for the case of Eye
      Movement Desensitization and Reprocessing (EMDR). Eye Movement Desensitization
      and Reprocessing has more randomized controlled studies conducted on its efficacy
      than any other treatment for trauma and thus, previous meta-analyses were
      evaluated. RESULTS AND CONCLUSIONS: It is concluded that these new therapies have
      offered no new scientifically valid theories of action, show only non-specific
      efficacy, show no evidence that they offer substantive improvements to extant
      psychiatric care, yet display many characteristics consistent with pseudoscience.

PMID- 15943645
TI  - Psychoanalysis, science and the seductive theory of Karl Popper.
AB  - OBJECTIVE: To present a critique of the ideas of Karl Popper, the philosopher of
      science, whose depiction of psychoanalysis as a pseudoscience is often used to
      justify attacks on psychoanalysis. METHOD: Published sources are used to provide
      a brief intellectual biography of Popper, a summary of his concept of science and
      a summary of criticisms of Popper's view of science. His depiction of
      psychoanalysis and Freud's reply are presented. Clinical, experimental and
      neurobiological research which refutes Popper's view is summarized. RESULTS:
      There is a vast scholarly published work critical of Popper's falsifiability
      criterion of science. Less recognized is Popper's misunderstanding and
      misrepresentation of psychoanalysis; his argument against it is logically flawed
      and empirically false. Even if Popper's theory of science is accepted, there is
      considerable clinical, experimental and neurobiological research in
      psychoanalysis which meets Popper's criterion of science. CONCLUSION: Attacks on
      psychoanalysis based on Popper's theory of science are ill-founded and reflect
      inadequate scholarship.

PMID- 15943646
TI  - Prevalence of psychoses on reception to male prisons in New South Wales.
AB  - OBJECTIVE: To estimate the prevalence of psychotic illnesses among men received
      to prisons in New South Wales. The study also sought to estimate the sensitivity
      and specificity of the psychosis screener in the Composite International
      Diagnostic Interview (CIDI-Auto). METHOD: The study was part of a larger study on
      psychiatric disorder in men received to New South Wales prisons. Using a
      structured questionnaire, the CIDI-Auto (modified), which included screening
      questions for psychotic illness, the prisoners who gave positive responses to the
      screening questions for psychosis as well as any subjects considered by the
      experienced clinicians performing the CIDI-Auto interviews to show features of a
      psychotic illness, were referred to the researchers for a clinical assessment.
      The clinical assessment included a review of all available information. RESULTS:
      Of the prisoners, 5.1% were thought to have definite psychotic illness and 1.9%
      to have possible psychotic illness. The psychosis screener was found to be
      neither sensitive nor specific. CONCLUSIONS: The rate of psychotic illness among
      people remanded to New South Wales prisons is between 10 and 14 times the rate
      found in a similar study in the wider community. The poor performance of the
      psychosis screener suggests that screening for psychotic illness on reception to
      prisons should be performed by clinically trained staff.

PMID- 15943647
TI  - Obstetric complications and transition to psychosis in an "ultra" high risk
      sample.
AB  - OBJECTIVE: An association between birth and pregnancy complications and the later
      development of schizophrenia has been described for decades and obstetric
      complications (OCs) have been proposed as a vulnerability marker for psychosis in
      line with the neurodevelopmental hypothesis of psychotic disorders. Previous
      studies of OCs have focused on established schizophrenia. In this study, the
      association between OCs and the development of psychotic disorder was studied in
      a group of 74 young people identified as being at very high risk for the first
      onset of psychosis. METHOD: The "ultra" high risk (UHR) cohort was identified by
      the presence of subthreshold psychotic symptoms, or a combination of first-degree
      relative with a psychotic disorder and recent functional decline. Thirty-eight
      per cent of the cohort developed an acute psychotic episode over the 12-month
      period after recruitment. As a component of a larger research study, the level of
      OCs experienced by the UHR cohort was assessed at intake. RESULTS: Obstetric
      complications were not associated with the later development of psychosis in the
      UHR group included in this study. CONCLUSIONS: This study does not support a role
      for OCs as a risk factor for the later development of psychosis; however, we
      cannot conclude that they should be completely ignored as a candidate risk factor
      for onset of psychosis. A number of weaknesses of the study suggest that it may
      be premature to dismiss OCs as a risk factor for the development of psychosis and
      further research is urged in this area.

PMID- 15943648
TI  - Changes in the pattern of substance abuse after the onset of psychosis.
AB  - OBJECTIVE: The aim of this study was to examine early signs of psychosis in
      patients suffering from both drug dependence and schizophrenia, compared to a
      control group of drug-addicted patients without a comorbid psychotic disorder,
      and to assess whether the presence of these signs was related to changes in the
      pattern of substance abuse. METHOD: In a rehabilitation hospital for young
      addicts, 32 patients with a comorbid diagnosis of schizophrenia and 30 patients
      without the diagnosis of a psychotic disorder, were assessed using the Interview
      for the Retrospective Assessment of the Onset of Schizophrenia. Information
      relating to 64 signs of early psychosis was collected from every patient. From
      the 64 signs, five groups of symptoms were defined: non-specific and precursor
      symptoms; non-specific and depressive symptoms; negative symptoms; positive
      symptoms; and impaired social adjustment. The semiquantitative pattern of
      substance abuse for each 1-year interval over the previous 10 years was
      investigated using the categories of chapter F1 of ICD-10 and including an
      additional category "biological drugs". The relationship between the pattern of
      substance abuse and the presence of early signs was assessed using anova and non
      parametric statistical methods. RESULTS: The results indicate that the defined
      pathological symptomatology greatly influences the pattern of consumption of
      psychoactive substances in both the psychosis group and the control group. The
      group factor exerted the greatest influence within the categories "biological
      drugs" and "other stimulants", where the "psychosis and addiction group" consumed
      significantly more than the control group. CONCLUSIONS: There is a subgroup of
      non-psychotic addicted patients whose pattern of psychoactive substance abuse is
      similar to that found in addicted patients suffering from schizophrenia. It may
      be helpful to systematically identify this subgroup with regard to possible
      therapeutic implications, particularly with regard to possible pharmacological
      treatment options.

PMID- 15943649
TI  - Expressed emotion as predictor of relapse in patients with comorbid psychoses and
      substance use disorder.
AB  - OBJECTIVE: Expressed emotion (EE) and substance use disorder predict relapse in
      psychosis, but there is little research on EE in comorbid samples. The current
      study addressed this issue. METHOD: Sixty inpatients with a DSM-IV psychosis and
      substance use disorder were recruited and underwent diagnostic and substance use
      assessment. Key relatives were administered the Camberwell Family Interview.
      RESULTS: Patients were assessed on the initial symptoms and recent substance use,
      and 58 completed the assessment over the following 9 months. High EE was observed
      in 62% of households. Expressed emotion was the strongest predictor of relapse
      during follow-up and its predictive effect remained in participants with early
      psychosis. A multivariate prediction of a shorter time to relapse entered EE,
      substance use during follow-up and (surprisingly) an absence of childhood
      attention deficit hyperactivity disorder. CONCLUSIONS: Since high EE is a common
      and important risk factor for people with comorbid psychosis and substance
      misuse, approaches to address it should be considered by treating clinicians.

PMID- 15943651
TI  - Relative contributions of psychiatric symptoms and neuropsychological functioning
      to quality of life in first-episode psychosis.
AB  - OBJECTIVE: To report on the relationship between quality of life (QOL),
      psychiatric symptoms and neuropsychological functioning in a sample of young
      people who have experienced a first episode of psychosis 2-3 years following
      initial presentation. METHOD: Fifty-one participants aged 15-27 years old
      completed the short form of the World Health Organization Quality of Life scale
      (WHOQOL-Bref), a self-report instrument assessing physical, psychological, social
      and environmental aspects of QOL. A comprehensive neuropsychological battery was
      administered. Measures of psychiatric symptoms including depression (as assessed
      by the Calgary Depression Scale), positive, negative and general psychopathology
      (as assessed by the Positive and Negative Syndrome Scale) were obtained. RESULTS:
      Multiple regression analyses were used to evaluate the ability of
      neuropsychological measures and psychiatric symptoms to predict QOL. When
      neuropsychological variables were considered on their own, cognitive flexibility,
      verbal fluency, verbal ability and sustained attention explained up to 28% of the
      variance in the four domains of QOL. However, in the presence of psychiatric
      symptoms, neuropsychological variables were no longer significant predictors for
      physical and psychological QOL; depression, general psychopathology and negative
      symptoms together explained up to 43% of the variance in QOL, with
      neuropsychological variables remaining significant for social and environmental
      QOL. CONCLUSIONS: In young people with their first episode of psychosis, QOL is
      more strongly related to levels of psychopathology, particularly depression, than
      neuropsychological deficits. This finding replicates previous studies in chronic
      schizophrenia that have suggested QOL is more strongly related to levels of
      psychopathology than the presence of neuropsychological deficits.

PMID- 15943650
TI  - Nutritional intervention to prevent weight gain in patients commenced on
      olanzapine: a randomized controlled trial.
AB  - OBJECTIVE: Olanzapine is the most commonly prescribed atypical antipsychotic
      medication in Australia. Research reports an average weight gain of between 4.5
      and 7 kg in the 3 months following its commencement. Trying to minimize this
      weight gain in a population with an already high prevalence of obesity, mortality
      and morbidity is of clinical and social importance. This randomized controlled
      trial investigated the impact of individual nutrition education provided by a
      dietitian on weight gain in the 3 and 6 months following the commencement of
      olanzapine. METHOD: Fifty-one individuals (29 females, 22 males) who had started
      on olanzapine in the previous 3 months (mean length of 27 days +/- 20) were
      recruited through Peninsula Health Psychiatric Services and were randomly
      assigned to either the intervention (n = 29) or the control group (n = 22).
      Individuals in the intervention group received six 1 hour nutrition education
      sessions over a 3-month period. Weight, waist circumference, body mass index
      (BMI) and qualitative measures of exercise levels, quality of life, health and
      body image were collected at baseline at 3 and 6 months. RESULTS: After 3 months,
      the control group had gained significantly more weight than the treatment group
      (6.0 kg vs 2.0 kg, p < or = 0.002). Weight gain of more than 7% of initial weight
      occurred in 64% of the control group compared to 13% of the treatment group. The
      control group's BMI increased significantly more than the treatment group's (2
      kg/m(2)vs 0.7 kg/m(2), p < or = 0.03). The treatment group reported significantly
      greater improvements in moderate exercise levels, quality of life, health and
      body image compared to the controls. At 6 months, the control group continued to
      show significantly more weight gain since baseline than the treatment group (9.9
      kg vs 2.0 kg, p < or = 0.013) and consequently had significantly greater
      increases in BMI (3.2 kg/m(2)vs 0.8 kg/m(2), p < or = 0.017). CONCLUSION:
      Individual nutritional intervention provided by a dietitian is highly successful
      at preventing olanzapine-induced weight gain.

PMID- 15943652
TI  - Self-administered instrument to measure the patient's experience of recovery
      after first-episode psychosis: development and validation of the Psychosis
      Recovery Inventory.
AB  - OBJECTIVE: Patients who are recovering from a first-episode psychosis face
      specific and complex issues that are related to their illness and treatment
      experiences, such as the appraisal of the extent of their recovery and the risk
      of relapse. Currently, no instrument provides a comprehensive assessment of these
      related attitudes. A novel self-administered rating scale for the measurement of
      key perceptions during the recovery stage after a first-episode psychosis is
      presented. The Psychosis Recovery Inventory (PRI) is designed to specifically
      address a number of closely related issues that are faced by patients who are
      recovering from a first-episode psychosis. METHOD: The process of development of
      the PRI involved the generation of items from qualitative interviews, the
      construction and refinement of these items and a validation study. The
      longitudinal stability of the PRI items was assessed in a test-retest reliability
      study in which 20 patients completed the retest within 4 weeks. The internal
      consistency and convergent validity of the PRI were evaluated by a comparison of
      the PRI subscale scores and the Scale to Assess Unawareness of Mental Disorder
      and Drug Attitude Inventory scores in a sample of 48 first-episode psychosis
      patients. RESULTS: The validation study shows that the PRI is an instrument with
      a good test-retest reliability, internal consistency and convergent validity.
      CONCLUSIONS: This pragmatic, low burden, self-administered scale can be applied
      in clinical and research settings to obtain reliable information on the attitudes
      of patients on a range of interrelated issues in the recovery stage that follows
      a first-episode psychosis.

PMID- 15943653
TI  - Investigation of consumer satisfaction with cognitive-behaviour therapy and
      sertraline in the treatment of adolescent depression.
AB  - OBJECTIVE: A new instrument, the Adolescent Depression Treatment Satisfaction
      Questionnaire (ADTSQ) was devised to measure the consumer satisfaction of
      depressed adolescents and their parents. The objectives of the paper were to
      present the psychometric properties of the ADTSQ and to investigate the relative
      consumer satisfaction with cognitive-behavioural therapy (CBT), sertraline (SRT)
      and a combined treatment of CBT and SRT (COMBINED) for the treatment of
      adolescent depression. In addition, participants were asked to rank their most
      preferred treatment from the following approaches: medication, individual
      counselling, group program and family therapy. METHOD: Thirty-eight adolescents
      with a unipolar depressive disorder and 37 parents who participated in a
      randomized clinical trial of CBT versus SRT versus COMBINED completed the ADTSQ
      following the completion of acute treatment. RESULTS: The ADTSQ was found to have
      high internal consistency and exploratory factor analysis detected three
      underlying factors. High levels of consumer satisfaction were reported by both
      adolescents and parents in all three treatments. Those treated with CBT
      treatments reported higher levels of skill acquisition than those treated with
      SRT. Of the four treatment approaches, most parents and adolescents rated
      individual counselling as their first preference. CONCLUSIONS: The ADTSQ is a
      useful measure of consumer satisfaction for depressed adolescents and their
      parents. CBT, SRT and COMBINED were shown to have high consumer satisfaction with
      CBT's higher skills training content reflected in the participants' reports.
      Individual counselling was perceived as the most favourable choice of treatment
      for adolescent depression. Although limitations associated with the measurement
      of consumer satisfaction and of the study are acknowledged, it is recommended
      that the inclusion of consumer satisfaction measures be considered in clinical
      trials that examine treatment efficacy.

PMID- 15943654
TI  - What patients and carers want to know: an exploration of information and resource
      needs in adult mental health services.
AB  - OBJECTIVE: The objectives of this study were to: (i) obtain baseline data on the
      extent of carer involvement across a representative sample of hospital and
      community patients within an integrated area health service; and (ii) examine
      perspectives on discharge planning and community care among patients and their
      carers to identify information and resources they consider important. METHOD:
      Over a 4-month period, inpatients before discharge and patients accessing
      community mental health services participated in face-to-face interviews.
      Information was collected about carer involvement and, with the patient's
      consent, the identified carer was sent a similar survey to determine demographics
      and information needs. This resulted in a representative sample of patients and
      carers accessing inpatient and community settings across a metropolitan mental
      health service. Support needs and carer burden were also assessed but are not
      reported here. RESULTS: A total of 407 interviews were completed, 207 in
      inpatient settings and 200 in the community. An inpatient response rate of 70%
      and a community response rate of 75% was achieved. Across both settings, 67% of
      patients identified a carer and a carer response rate of 28% was then obtained.
      We found carers and patients have different priorities regarding the information
      they want and information is often not provided to carers. Furthermore, patients
      were more confident in their ability to manage their mental health in the
      community than carers. CONCLUSIONS: This study yielded important baseline data
      about the number of patients who have a carer. We were also able to determine
      that routine clinical information provided to patients and carers is inadequate
      from their perspective. It is anticipated that this initiative will assist
      ongoing service planning and improve partnerships with patients and their carers.

PMID- 15943655
TI  - Role of stigma and attitudes toward help-seeking from a general practitioner for
      mental health problems in a rural town.
AB  - OBJECTIVE: To examine the role of perceived stigma and attitudes to seeking care
      in predicting help-seeking from a general practitioner (GP) for mental health
      problems. METHOD: A cross-sectional survey in 2002 with self-report
      questionnaires assessing current levels of symptomatology, disability, attitudes
      towards mental illness, knowledge of prevalence and causes of mental illness,
      contact with mental illness and help-seeking behaviour and preferences and
      attitudes toward seeking professional psychological help. RESULTS: No significant
      relationship was found between symptom measures and measures of disability and
      help-seeking. Variables positively associated with general attitudes to seeking
      professional psychological help were: lower perceived stigma, and biological
      rather than person-based causal attributions for schizophrenia. Willingness to
      discuss mental health issues with a GP was predicted by the perceived helpfulness
      of the GP and by no other variable. CONCLUSIONS: Causal attributions and
      perceived stigma rather than participants' levels of symptomatology and
      disability influence attitudes to help-seeking for mental health issues. Efforts
      to improve attitudes to help-seeking should focus on reducing stigma and
      improving mental health literacy regarding the causes of disorders.

PMID- 15943656
TI  - Outcomes of an early psychosis intervention program.

PMID- 15943657
TI  - Schizophrenia in the early middle ages: some negative evidence.

PMID- 15943659
TI  - Maintenance treatment of bipolar disorder: concerning results from a nationwide
      questionnaire survey in Finland.

PMID- 15943661
TI  - Potential risks associated with high-dose valproate in pregnancy in psychiatric
      patients.

PMID- 15943665
TI  - Research in the high-stakes era.
AB  - The federal No Child Left Behind Act (NCLB; 2001), mandating standardized testing
      in public schools, provides researchers with unprecedented opportunities for
      scientific comparison. At the same time, the climate of high-stakes testing
      encouraged by the law merits empirical scrutiny from psychologists across an
      array of specialties. If researchers wish to advance policy through psychological
      science, they must take care to construct research designs that are meaningful to
      policymakers and professionals in other disciplines. The present study used data
      from 1,450 Virginia schools to provide a model of scientifically grounded
      research that is also informed by current legal and political contexts. Results
      indicate that student poverty and geography are associated with differential
      access to highly qualified teachers, and that differential access to qualified
      teachers is uniquely associated with performance on high-stakes achievement
      tests. Psychologists, with their unique training, are encouraged to take a more
      active role in using NCLB data.

PMID- 15943666
TI  - Avoiding the death risk of avoiding a dread risk: the aftermath of March 11 in
      Spain.
AB  - Abstract-After the airplane attacks of September 11, 2001, in the United States,
      many Americans drove instead of flying, to avoid the risk of terrorism. As a
      result, there were extra car accidents in which many people died. This study
      tested whether a similar effect occurred in Spain after the train bombings of
      March 11, 2004, in Madrid. Data on train travel, highway traffic, and fatal
      highway accidents were analyzed for the months immediately following March 11.
      Results show that, like Americans, Spaniards avoided the dread risk of terror
      attacks, but unlike Americans, they did not confront the death risk of fatal
      accidents instead. A sociopolitical interpretation for these findings is offered.

PMID- 15943667
TI  - Dynamic influences of culture on cooperation in the prisoner's dilemma.
AB  - This study tested whether priming of cultural symbols activates cultural
      behavioral scripts and thus the corresponding behaviors, and also whether the
      behaviors activated are context-specific. Specifically, to activate the cultural
      knowledge of Chinese-American bicultural participants, we primed them with
      Chinese cultural icons or American cultural icons. In the control condition, we
      showed them geometric figures. Then, the participants played the Prisoner's
      Dilemma game with friends or strangers (the context manipulation). As expected,
      participants showed more cooperation toward friends when Chinese cultural
      knowledge was activated than when American cultural knowledge was activated. By
      contrast, participants showed a similarly low level of cooperation toward
      strangers after both Chinese and American culture priming. These findings not
      only support previous evidence on culture priming of social judgment and self
      construals, but also (a) provide the first evidence for the effects of culture
      priming on behaviors and (b) demonstrate the boundary condition of culture
      priming.

PMID- 15943668
TI  - Investment behavior and the negative side of emotion.
AB  - Can dysfunction in neural systems subserving emotion lead, under certain
      circumstances, to more advantageous decisions? To answer this question, we
      investigated how normal participants, patients with stable focal lesions in brain
      regions related to emotion (target patients), and patients with stable focal
      lesions in brain regions unrelated to emotion (control patients) made 20 rounds
      of investment decisions. Target patients made more advantageous decisions and
      ultimately earned more money from their investments than the normal participants
      and control patients. When normal participants and control patients either won or
      lost money on an investment round, they adopted a conservative strategy and
      became more reluctant to invest on the subsequent round; these results suggest
      that they were more affected than target patients by the outcomes of decisions
      made in the previous rounds.

PMID- 15943669
TI  - Reversibility of the other-race effect in face recognition during childhood.
AB  - Early experience with faces of a given racial type facilitates visual recognition
      for this type of face relative to others. To assess whether this so-called other
      race effect can be reversed by subsequent experience with new types of faces, we
      tested adults of Korean origin who were adopted by European Caucasian families
      when they were between the ages of 3 to 9. The adoptees performed a face
      recognition task with photographs of Caucasian and Asian faces. They performed
      exactly like a control group of French participants, identifying the Caucasian
      faces better than the Asiatic ones. In contrast, a control group of Koreans
      showed the reverse pattern. This result indicates that the face recognition
      system remains plastic enough during childhood to reverse the other-race effect.

PMID- 15943670
TI  - Aging neuromodulation impairs associative binding: a neurocomputational account.
AB  - Relative to young adults, older adults are particularly impaired in episodic
      memory tasks requiring associative binding of separate components into compound
      episodes, such as tasks requiring item-context and item-item binding. This
      associative-binding deficit has been attributed to senescent changes in frontal
      hippocampal circuitry but has not been formally linked to impaired
      neuromodulation involving this circuitry. Previous neurocomputational work showed
      that impaired neuromodulation could result in less distinct neurocognitive
      representations. Here we extend this computational principle to simulate aging
      related deficits in associative binding. As expected, networks with simulated
      deficiency in neuromodulation resulted in less distinct internal representations
      than did networks simulating the processing and performance of young adults, and
      were also more impaired under task conditions that required associative binding.
      The findings suggest that senescent changes in neuromodulatory mechanisms may
      play a basic role in aging-related impairment in associative binding by reducing
      the efficacy of distributed conjunctive coding.

PMID- 15943671
TI  - Linguistic constraints on statistical computations: the role of consonants and
      vowels in continuous speech processing.
AB  - Speech is produced mainly in continuous streams containing several words.
      Listeners can use the transitional probability (TP) between adjacent and non
      adjacent syllables to segment "words" from a continuous stream of artificial
      speech, much as they use TPs to organize a variety of perceptual continua. It is
      thus possible that a general-purpose statistical device exploits any speech unit
      to achieve segmentation of speech streams. Alternatively, language may limit what
      representations are open to statistical investigation according to their specific
      linguistic role. In this article, we focus on vowels and consonants in continuous
      speech. We hypothesized that vowels and consonants in words carry different kinds
      of information, the latter being more tied to word identification and the former
      to grammar. We thus predicted that in a word identification task involving
      continuous speech, learners would track TPs among consonants, but not among
      vowels. Our results show a preferential role for consonants in word
      identification.

PMID- 15943672
TI  - Measurement of individual differences: lessons from memory assessment in research
      and clinical practice.
AB  - An examination of test manuals and published research indicates that widely used
      memory tests (e.g., Verbal Paired Associates and Word List tests of the Wechsler
      Memory Scale, Rey Auditory Verbal Learning Test, and California Verbal Learning
      Test) are afflicted by severe ceiling effects. In the present study, the true
      extent of memory ability in healthy young adults was tested by giving 208 college
      undergraduates verbal paired-associate and verbal learning tests of various
      lengths; the findings demonstrate that healthy adults can remember much more than
      is suggested by the normative data for the memory tests just mentioned. The
      findings highlight the adverse effects of low ceilings in memory assessment and
      underscore the severe consequences of ceiling effects on score distributions,
      means, standard deviations, and all variability-dependent indices, such as
      reliability, validity, and correlations with other tests. The article discusses
      the optimal test lengths for verbal paired-associate and verbal list-learning
      tests, shows how to identify ceiling-afflicted data in published research, and
      explains how proper attention to this phenomenon can improve future research and
      clinical practice.

PMID- 15943673
TI  - When good things go bad: the reflex physiology of defense.
AB  - For humans, the threat of painful shock greatly potentiates the reflexive startle
      blink. Moreover, viewing unpleasant, compared with pleasant, pictures also
      prompts heightened startle reflexes, suggesting that the startle reflex indexes
      general defensive activation. In this study, pleasant or unpleasant pictures were
      used to signal shock threat in order to explore how previous affective
      associations modulate new defensive reactions. When cuing threat of shock,
      pleasant and unpleasant pictures prompted physiological profiles consistent with
      defensive activation, indicating that threat of shock renders previously pleasant
      cues aversive. For unpleasant pictures only, defensive startle was potentiated
      even when these cues signaled safety. Taken together, the data indicate that (a)
      regardless of their intrinsic affective meaning, cues signaling shock threat
      prompt somatic and autonomic reactions consistent with defense, and that (b)
      intrinsically unpleasant cues continue to prompt defensive activation even when
      the context of their presentation is specifically non-threatening.

PMID- 15943674
TI  - Constructed criteria: redefining merit to justify discrimination.
AB  - This article presents an account of job discrimination according to which people
      redefine merit in a manner congenial to the idiosyncratic credentials of
      individual applicants from desired groups. In three studies, participants
      assigned male and female applicants to gender-stereotypical jobs. However, they
      did not view male and female applicants as having different strengths and
      weaknesses. Instead, they redefined the criteria for success at the job as
      requiring the specific credentials that a candidate of the desired gender
      happened to have. Commitment to hiring criteria prior to disclosure of the
      applicant's gender eliminated discrimination, suggesting that bias in the
      construction of hiring criteria plays a causal role in discrimination.

PMID- 15943675
TI  - Investigating true and false confessions within a novel experimental paradigm.
AB  - The primary goal of the current study was to develop a novel experimental
      paradigm with which to study the influence of psychologically based interrogation
      techniques on the likelihood of true and false confessions. The paradigm involves
      guilty and innocent participants being accused of intentionally breaking an
      experimental rule, or "cheating." In the first demonstration of this paradigm, we
      explored the influence of two common police interrogation tactics: minimization
      and an explicit offer of leniency, or a "deal." Results indicated that guilty
      persons were more likely to confess than innocent persons, and that the use of
      minimization and the offer of a deal increased the rate of both true and false
      confessions. Police investigators are encouraged to avoid interrogation
      techniques that imply or directly promise leniency, as they appear to reduce the
      diagnostic value of any confession that is elicited.

PMID- 15943676
TI  - The distribution and development of handedness for manual gestures in captive
      chimpanzees (Pan troglodytes).
AB  - This article describes the distribution and development of handedness for manual
      gestures in captive chimpanzees. Data on handedness for unimanual gestures were
      collected in a sample of 227 captive chimpanzees. Handedness for these gestures
      was compared with handedness for three other measures of hand use: tool use,
      reaching, and coordinated bimanual actions. Chimpanzees were significantly more
      right-handed for gestures than for all other measures of hand use. Hand use for
      simple reaching at 3 to 4 years of age predicted hand use for gestures 10 years
      later. Use of the right hand for gestures was significantly higher when gestures
      were accompanied by a vocalization than when they were not. The collective
      results suggest that left-hemisphere specialization for language may have evolved
      initially from asymmetries in manual gestures in the common ancestor of
      chimpanzees and humans, rather than from hand use associated with other, non
      communicative motor actions, including tool use and coordinated bimanual actions,
      as has been previously suggested in the literature.

PMID- 15943677
TI  - Still much to learn about confidence intervals: reply to Rounder and Morey
      (2005).

PMID- 15943678
TI  - A freezing-like posture to pictures of mutilation.
AB  - Postural sway and heart rate were recorded in young men viewing emotionally
      engaging pictures. It was hypothesized that they would show a human analog of
      "freezing" behavior (i.e., immobility and heart rate deceleration) when
      confronted with a sustained block of unpleasant (mutilation) images, relative to
      their response to pleasant/arousing (sport action) or neutral (objects) pictures.
      Volunteers stood on a stabilometric platform during picture viewing.
      Significantly reduced body sway was recorded during the unpleasant pictures,
      along with increased mean power frequency (indexing muscle stiffness). Heart rate
      during unpleasant pictures also showed the expected greater deceleration. This
      pattern resembles the "freezing" and "fear bradycardia" seen in many species when
      confronted with threatening stimuli, mediated by neural circuits that promote
      defensive survival.

PMID- 15943679
TI  - The effects of fear on performance monitoring and attentional allocation.
AB  - Evidence from event-related potential (ERP) studies indicates abnormal error
      processing and attentional allocation in "trait"-anxious individuals. However,
      few studies have been conducted that evaluate relevant ERP components during the
      induction of an anxious state (i.e., fear). In the present study, ERPs were
      measured in 16 undergraduates during control and fear induction conditions to
      examine the effects of fear on error processing and attentional allocation.
      Despite comparable performance in both experimental conditions, the ERP data
      indicated reductions in attentional allocation and error salience during fear
      induction. Fear did not appear to directly alter early error processing, as
      indicated by the error-related negativity, however. The implication of these
      results for understanding how trait and state anxiety may affect error processing
      and attentional allocation are discussed.

PMID- 15943680
TI  - Life events and hemodynamic stress reactivity in the middle-aged and elderly.
AB  - Recent versions of the reactivity hypothesis, which consider it to be the product
      of stress exposure and exaggerated hemodynamic reactions to stress that confers
      cardiovascular disease risk, assume that reactivity is independent of the
      experience of stressful life events. This assumption was tested in two
      substantial cohorts, one middle-aged and one elderly. Participants had to
      indicate from a list of major stressful life events up to six they had
      experienced in the previous 2 years. They were also asked to rate how disruptive
      and stressful they were, at the time of occurrence and now. Blood pressure and
      pulse rate were measured at rest and in response to acute mental stress. Those
      who rated the events as highly disruptive at the time of exposure and now
      exhibited blunted systolic blood pressure reactions to acute stress. The present
      results suggest that acute stress reactivity may not be independent of stressful
      life events experience.

PMID- 15943681
TI  - Vagal withdrawal to a sad film predicts subsequent recovery from depression.
AB  - Cardiac vagal tone, as indexed by abnormalities in the level and/or reactivity of
      respiratory sinus arrhythmia (RSA), has been related to psychiatric impairment,
      including risk for depression. Longitudinal studies of depression have focused on
      RSA levels and have found mixed support for the hypothesis that low RSA levels
      predict a more pernicious course of depression. The current investigation focuses
      on the relation between RSA reactivity and the course of depression. We measured
      depressed persons' RSA reactivity to sadness-, fear-, and amusement-inducing
      emotion films and reassessed participants' diagnostic status 6 months later.
      Depressed persons who exhibited a higher degree of vagal withdrawal to the sad
      film were more likely to recover from depression. Implications for the study of
      RSA in depression are discussed.

PMID- 15943682
TI  - The effect of glucose and mental stress on cutaneous microvascular endothelial
      function.
AB  - Glucose and mental stress, independently, have been found to impair arterial
      endothelial function (an indicator of vascular health). The present study sought
      to determine whether the combination of glucose and stress would have a greater
      effect on microvascular endothelial function than each on its own. To assess
      endothelial function, surges in skin blood flow (reactive hyperemia), following
      the release of cuff pressure to the upper arm at 200 mmHg for 5 min, were
      measured with laser Doppler flowmetry in 40 young, healthy females. Endothelial
      function did not change significantly following a 5-min mathematics stressor or
      the consumption of 75 g of glucose. However, the combination of glucose and
      stress impaired endothelium-dependent dilatation 30 min after glucose
      consumption. These findings suggest that combinations of vascular risk factors
      may be more threatening to cardiovascular health than singularly occurring
      factors.

PMID- 15943683
TI  - Ethnicity, sex, trait anger, and nocturnal blood pressure decline.
AB  - This study examined the relationship of trait anger to nocturnal blood pressure
      decline among Singaporean young adults. One hundred forty-nine participants (51
      Chinese, 51 Malays, 47 Indians, 49.7% men) participated in 24-h ambulatory
      monitoring for blood pressure and hemodynamic measures. Significant interactions
      were obtained between ethnicity and trait anger for systolic blood pressure and
      mean arterial pressure such that trait anger was significantly and negatively
      related to nocturnal blood pressure decline for Indians whereas this was not true
      for Chinese or Malays. Significant sex x trait anger interactions were obtained
      for systolic blood pressure, diastolic blood pressure, and mean arterial pressure
      in which trait anger was negatively related to blood pressure decline for men but
      not for women. Overall the results suggest that trait anger is a significant
      factor affecting nocturnal blood pressure decline particularly among Indians and
      men.

PMID- 15943684
TI  - Effects of background noise on the human startle reflex and prepulse inhibition.
AB  - Three experiments investigated whether background noise modified the startle
      blink reflex and prepulse inhibition (PPI). In Experiment 1 background noise was
      about 28 (ambient), 40, and 60 dB; in Experiments 2 and 3 background noise was
      ambient and 60 dB. Prepulses were 70-dB tones (Experiments 1 and 3) or a tactile
      stimulus (Experiment 2). Startle-eliciting stimuli were 94-dB noise (Experiments
      1 and 2) or an airpuff to the face (Experiment 3). Prepulses were presented at
      stimulus onset asynchronies of 30, 60, 120, 240, and 2000 ms relative to the
      startle-eliciting stimulus. Background noise of 60 dB had no effect on control
      reflexes, whereas 40-dB background noise increased control reflexes. Background
      noise decreased PPI, but only when an acoustic stimulus was used as prepulse. In
      sum, the findings show that background noise reduces the signal-to-noise ratio of
      acoustic prepulses and decreases their modulatory effect on the startle reflex.

PMID- 15943685
TI  - Time's arrow and pupillary response.
AB  - The psychological arrow of time refers to our experience of the forward temporal
      progression of all natural processes. To investigate whether and how time's arrow
      is mentally coded in individual everyday events, a relatedness judgment task was
      used. The items each consisted of a verb (probe) and an adjective or participle
      (target). The temporal orientation between probe and target was varied either
      corresponding to the chronological orientation (e.g., shrinking-small) or
      corresponding to the reverse orientation (e.g., shrinking-large). Reaction times,
      error rates, and pupillary responses were recorded. Chronological items were
      processed faster than reverse items. These findings suggest that time's arrow is
      mentally coded in single everyday events. Pupil dilation and results of principal
      component analyses suggest top-down influences in the processing of temporally
      related items.

PMID- 15943686
TI  - Cross-modal generality of the gating deficit.
AB  - Auditory P50/M50 paired-click studies have established an association between
      schizophrenia and impaired sensory gating in the auditory modality. However, the
      presumed cross-modal generality of the gating deficit has received little study.
      The present study examined gating in area 3b of primary somatosensory cortex to
      evaluate patients' somatosensory gating at this first stage of cortical
      processing. One hundred twenty-two channels of magnetoencephalography (MEG) data
      were collected from 27 subjects with chronic schizophrenia and 21 controls during
      a somatosensory paired-pulse paradigm with a 75- or 500-ms interstimulus
      interval. M20 somatosensory responses were localized using magnetic source
      imaging, and a gating ratio was calculated. In a subset of these subjects, MEG
      was also done for the standard auditory paradigm to assess M50 gating. Patients
      showed abnormal auditory M50 gating but normal somatosensory M20 gating. Results
      argue against a cross-modal gating deficit in primary somatosensory cortex.

PMID- 15943687
TI  - Electrophysiological correlates of change detection.
AB  - To identify electrophysiological correlates of change detection, event-related
      brain potentials (ERPs) were recorded while participants monitored displays
      containing four faces in order to detect a face identity change across successive
      displays. Successful change detection was mirrored by an N2pc component at
      posterior electrodes contralateral to the side of a change, suggesting close
      links between conscious change detection and attention. ERPs on undetected-change
      trials differed from detected-change and no-change trials. We suggest that short
      latency ERP differences between these trial types reflect trial-by-trial
      fluctuations in advance task preparation, whereas differences in the P3 time
      range are due to variations in the duration of perceptual and decision-related
      processing. Overall, these findings demonstrate that ERPs are a useful tool for
      dissociating processes underlying change blindness and change detection.

PMID- 15943688
TI  - Automatic word form processing in masked priming: an ERP study.
AB  - Five prime types (unrelated words, pronounceable nonwords, illegal strings of
      letters, false fonts, or neutral strings of Xs) preceded word and nonword targets
      in a masked priming study designed to investigate word form processing as indexed
      by event-related potentials (ERPs). Participants performed a lexical decision
      task on targets. In the 150-250-ms epoch at fronto-central, central, and temporo
      parietal sites ERPs were smallest to targets preceded by words and nonwords,
      followed by letter strings, false fonts, and finally neutral primes. This
      refractory pattern sensitive to orthography supports the view that ERPs in the
      150-250-ms epoch index activation of neural systems involved in word form
      processing and suggests that such activation may be graded, being maximal with
      word-like stimuli and relatively reduced with alphabet-like stimuli. Further,
      these results from a masked priming paradigm confirm the automatic nature of word
      form processing.

PMID- 15943689
TI  - Subjective and objective probability effects on P300 amplitude revisited.
AB  - Does objective probability affect P300 size independently and in addition to
      subjective probability? The latter was manipulated by the number of stimuli
      presented and classification task. Five groups saw target and frequent stimuli.
      Two saw these with p=.2 or .067, with two different button presses. Three groups
      saw two additional nontarget stimuli each with p=.067. One group pressed a
      different button for each stimulus. A second group pressed one button for the
      three oddballs, another for the frequent. A third critical group pressed one
      button for the target and another for other stimuli. In this group, P300 was
      larger for targets versus nontargets, and larger for nontargets versus frequents.
      Although nontargets were classified with frequents, their actual low probability
      distinguished them from frequents, and their subjective probability distinguished
      them from targets. Therefore, actual and subjective probability effects were
      independently found.

PMID- 15943690
TI  - The effect of removal of seminal plasma, egg yolk level and season on sperm
      freezability of canary buck (Capra hircus).
AB  - Goat semen is different from that of other domestic species in its limited
      tolerance to the inclusion of egg yolk in the freezing medium, and this tolerance
      depends on the presence of enzymes in the seminal plasma that react with egg
      yolk, producing toxic compounds to the spermatozoa. Moreover, the goat is a
      seasonal breeder that shows variations in semen quality throughout the year, and
      those variations may affect semen freezability; hence in freezing protocols, for
      instance, removal of seminal plasma (washing) yields varying results. This work
      was designed to study this problem in Canary goats: semen from six males was
      collected in spring, autumn or winter, washed or non-washed, diluted in a
      freezing extender with 1.5, 6 or 12% egg yolk, frozen, and thawed after 2 days, 2
      or 6 months of cryopreservation. The effect of egg yolk concentration in the
      freezing extender was far more important than the effect of washing or season on
      sperm cryosurvival. The quality of frozen-thawed semen tended to improve as egg
      yolk concentration increased regardless of the effects of season, washing or
      period of cryopreservation. Washing produced a positive effect on frozen-thawed
      semen collected during spring or autumn, but the difference decreased as the
      concentration of yolk increased. However, washing produced a negative effect on
      frozen-thawed semen collected during winter, diluted with either 6 or 12% egg
      yolk. There was no apparent seasonal effect on gross measures of sperm production
      but the seasonal effect was ever present and was reinforced by freezing.

PMID- 15943691
TI  - Sex identification of the black swan (Cygnus atratus) using the locus-specific
      PCR and implications for its reproduction.
AB  - Over the last 4-5 years the small captive population of black swans (Cygnus
      atratus) has consistently failed to reproduce at the Chengdu Research Base of
      Giant Panda Breeding. The probable cause was hypothesized to be an abnormal sex
      distribution of the population. The black swan is an example of a sexually
      monomorphic species. The locus-specific polymerase chain reaction (PCR) approach
      based on the chromo-helicase-DNA-binding 1 (CHD1) gene, was adopted for the sex
      determination of the black swans. For this purpose, F1, F2 and R primers were
      designed using the primerselect software for amplification of the CHD1 gene
      region. DNA agarose gel electrophoresis showed that the female control displayed
      two bands, whereas only a single band was found in the male control. Sequence
      analyses of all seven unknown sex black swans demonstrated the sex-specific DNA
      band for female. Therefore, it was inferred that all the individuals of the black
      swan population are females, which has resulted in unfertilized eggs and
      reproduction failure. This method can be extended to the sexing of other
      monomorphic avian species and will assist in the design of breeding projects.

PMID- 15943692
TI  - Effects of clinical mastitis on ovarian function in post-partum dairy cows.
AB  - Mastitis-induced ovarian abnormalities were studied in a field trial. At 1-3 day
      after calving, > or = 2 parity cows not affected with chronic recurrent mastitis
      and yielding < 400,000/ml somatic cell count (SCC) individual milk in the
      previous lactation, were enrolled in the study. Thereafter milk samples were
      collected three times weekly for 95-100 day for progesterone (P4) assay.
      Individual P4 profiles were used to monitor ovarian cyclicity. When mastitis was
      diagnosed in the first 80 day post-partum (pp), clinical signs were recorded and
      scored, and aseptic milk samples were taken to identify the mastitis pathogens.
      Depending on the isolated pathogens the cows were blocked into one of the three
      sub-groups affected by either Gram-positive (GP), or Gram-negative (GN) bacteria,
      or of those with no detected pathogens (NDP). Cows suffering from any type of
      mastitis between days 15 and 28 (n = 27) showed a delay in the onset of ovarian
      cyclicity, and estrus was postponed compared to cows affected during the first 14
      day pp (n = 59) and controls (n = 175) (38.6 +/- 2.3 vs 33.4 +/- 2.1 and 32.0 +/-
      1.0 day, respectively, for onset of ovarian cyclicity and 90.7 +/- 2.5 vs 80.2 +/
      2.8 and 83.9 +/- 2.1 day, respectively, for estrus; both p < 0.05). The
      percentage of cows ovulating by day 28 was lower in those affected by mastitis
      between days 14 and 28 compared to cows between days 1 and 14 and controls (22.2%
      vs 47.5 and 50.3%, respectively; p < 0.05). A significantly higher rate of
      premature luteolysis was observed in GN + NDP compared to GP mastitis and healthy
      cows (46.7% vs 8.3 and 2.0%, respectively; p < 0.001). If the mastitis outbreak
      occurred during the follicular phase, the duration of this cycle segment was
      lengthened in GN + NDP mastitis compared to GP mastitis and healthy cows (10.8 +/
      0.9 vs 7.9 +/- 0.1 and 7.2 +/- 0.1, respectively; p < 0.001). The results
      indicate that mastitis can affect the resumption of ovarian activity in pp dairy
      cows. Mastitis may also impair reproduction also in cyclic cows: this effect can
      be the consequence of premature luteolysis or a prolonged follicular phase.

PMID- 15943693
TI  - Relation between physical properties of the zona pellucida and viability of
      bovine embryos after slow-freezing and vitrification.
AB  - In vitro-produced bovine morulae/blastocyst embryos (n = 119) were slow-frozen
      and vitrified and the physical alterations of the zona pellucida (ZP) was
      observed by scanning electron microscopy (SEM) to find an explanation for the
      loss of developmental capacity of the embryos after freezing/thawing. A control
      group was provided, in which embryos (n = 38) were neither frozen nor vitrified.
      Embryos were in vitro-cultured in a standard CO2 Heraeus incubator and their
      viability was assessed 24 and 48 h after the start of culture, evaluating their
      morphological aspect. After 24 h of culture, embryo survival rate for slow
      freezing/thawed (n = 23), vitrified/thawed (n = 20) and control embryos (n = 20)
      was 39, 27 and 90%, and 35, 14 and 65% after 48 h of culture, respectively. For
      evaluation of physical changes occurring in ZP, 20 embryos were slow-frozen, 18
      were vitrified and 18 were used as control. All embryos were fixed, dried and
      examined under an SEM. Embryo's diameter, as well as the number of pores and
      their diameter was measured in squares of 6.4 microm width. We observed that, on
      average, the diameter of the embryos (92.26 +/- 10.15 microm) did not differ
      significantly among all embryos. As far as the diameter of the pores in the outer
      surface of the ZP is concerned, the results revealed a significant difference (P
      < 0.05) between control (0.48 +/- 0.0025 microm), slow-frozen (0.34 +/- 0.0007
      microm) and vitrified (0.27 +/- 0.0006 microm) embryos. For the number of pores,
      statistical differences (p < 0.05) were observed between control and vitrified
      embryos (45.4 +/- 7.3 vs 38.2 +/- 8.2). It is possible that ZP functions as a
      barrier which is positive when dealing with pathogens, but is harmful when
      nutrients were supplied from the outside, especially at 48 h of culture. Results
      indicate that the steps of cryopreservation cause alterations in ZP, with
      irreversible damage on the further developmental competence of bovine embryos.

PMID- 15943694
TI  - Chronological appearance of apoptosis in bovine embryos reconstructed by somatic
      cell nuclear transfer from quiescent granulosa cells.
AB  - Efficiency of cloning has remained low and in spite of attempts to improve this
      technology, many reconstructed embryos do not implant or are lost during early
      pregnancy. Chromosomal aberrations, deviant gene expression patterns and abnormal
      regulation of cell death may be involved in this increased early embryonic loss.
      Here, we investigate the chronological onset of both apoptotic changes in nuclear
      morphology and DNA degradation [detected by transferase-mediated dUTP nick-end
      labelling (TUNEL) reaction] in bovine two-cell- to blastocyst-stage embryos. Such
      embryos were generated either by reconstruction with nuclear transfer from
      quiescent granulosa cells or by regular in vitro embryo production. Nuclear
      condensation was observed from the two-cell stage and TUNEL labelling was
      observed from the six-cell stage in reconstructed embryos, whereas nuclear
      condensation was evident from the eight-cell stage and TUNEL labelling from the
      13-cell stage in embryos derived in vitro. Furthermore, reconstructed embryos
      displayed elevated ratios of embryos containing apoptotic nuclei at pre
      compaction stages and higher indices of apoptotic nuclei in morula and blastocyst
      stages when compared with in vitro-produced embryos.

PMID- 15943695
TI  - Leptin, GH, PRL, insulin and metabolic parameters throughout the dry period and
      lactation in dairy cows.
AB  - Leptin may play a role in the endocrine-metabolic processes that guarantee the
      physiological course of lactation in dairy cattle. This study was aimed at
      determining the changes in plasma concentrations of leptin and some of the main
      hormones and metabolites involved in the lactogenetic process in high-yielding
      dairy cows throughout lactation; we also wanted to assess whether leptin
      secretion is subjected to seasonal influences. Blood samples were collected from
      23 Italian Friesian dairy cows from the end of a lactation to the ninth month of
      the subsequent one; in addition, blood was sampled from 47 dairy cows in
      different phases of lactation during February and July. Plasma concentrations of
      leptin, growth hormone (GH), insulin, prolactin (PRL), glucose, non-esterified
      fatty acids (NEFA) and urea were quantified by either validated radioimmunoassay
      (RIA) or enzymatic colorimetric methods. At the beginning of lactation, GH
      concentrations significantly increased, while a significant reduction occurred in
      leptin and insulin. This endocrine condition, such as the significant increase in
      NEFA plasma concentrations, is indicative of a marked lipid mobilization. In the
      more advanced stages of lactation, when both energy and protein balances become
      positive, leptin plasma concentrations increased, whereas GH and NEFA
      concentrations declined. During the summer months, a significant increase in
      leptin plasma concentrations, irrespective of the phase of lactation, was
      observed. Collectively, our findings suggest that, in dairy cows, leptin may
      represent a 'metabolic signal' of animal's status of fattening and nutritional
      level; in addition, leptin seems to be influenced by photoperiod and
      environmental temperature.

PMID- 15943696
TI  - Night-time melatonin secretion and seasonally delayed puberty in gilts.
AB  - This study was conducted to determine whether the seasonal delay in puberty in
      autumn is driven by individual differences in night-time melatonin secretion in
      domestic gilts at the attainment of puberty. A group of spring-born gilts (n =
      30) were expected to reach puberty in autumn by the age of 7 months. Eighteen of
      these gilts were selected in pairs on the basis of matched days of birth. By the
      expected time, half of the animals showed oestrous symptoms (group CYCLING, n =
      9) with the rest remaining silent (group SILENT, n = 9). Afterwards, all gilts
      were fitted with indwelling jugular catheters for frequent blood sampling. Blood
      samples were collected from all animals three times during the day followed by
      three times in the night at 2-h intervals for 48 h. The samples were analysed by
      a commercial radioimmunoassay (RIA). The results show a consistent 25-fold rise
      (on average) in night-time melatonin concentration in every animal sampled with
      group averages ranging from 0.28 +/- 0.04 to 0.37 +/- 0.06 pg/ml at day and from
      10.20 +/- 2.16 to 10.67 +/- 0.05 pg/ml at night. Night-time group mean values
      between CYCLING and SILENT gilts did not differ significantly (10.26 +/- 0.67 and
      10.38 +/- 0.94 for the CYCLING; 10.67 +/- 0.05 and 10.20 +/- 2.16 for the
      SILENT). When 10 pg/ml was used as a threshold value, six individuals did not
      reach it during the night (low responders). Two of these gilts were CYCLING and
      four were SILENT. In conclusion, the results presented imply no involvement of
      the level of night-time melatonin concentration in the seasonal delay of puberty
      in gilts.

PMID- 15943697
TI  - Expression of oestrogen receptors alpha and beta and of aromatase in the testis
      of immature and mature boars.
AB  - The boar testis secretes high amounts of oestrogens. In order to test for a
      likely local significance, we investigated the expression of oestrogen receptors
      (ER) in immature and mature boar testes using immunohistochemistry (IHC), in
      vitro and in situ reverse transcription-polymerase chain reaction (RT-PCR).
      Samples were from 25 boars castrated at ages of 50, 100, 150, 200 and 250 days.
      Mouse monoclonal primary antibodies against porcine ERalpha (clone HT227), human
      ERbeta1 (clone PPG5/10) and human P450 aromatase (clone SM1671P) were used.
      Expression of the mRNA was tested utilizing primers specific for the respective
      porcine mRNA sequences. ER immunoreactivity was exclusively localized to the
      nuclei. In immature boars, 90.6 +/- 1.2% of prespermatogonia and 71.0 +/- 2.6% of
      the Leydig cells showed a strong staining for ERalpha; 95.5 +/- 3.5% of the
      prespermatogonia but none of the Leydig and Sertoli cells were ERbeta-positive.
      In mature boars a strong staining for the ERbeta was observed in virtually all
      Sertoli, Leydig and germ cells, except for the elongating/ed spermatids, which
      were clearly negative; for the ERalpha, strong immunoreaction signals were
      restricted to spermatogonia and primary spermatocytes with 93.6 +/- 2.7% of these
      cells being positive; distinctly less intensive signals were observed in 51.4 +/-
      0.27% of the secondary spermatocytes, round spermatids and Leydig cells. In vitro
      RT-PCR was positive for both receptors and results of in situ RT-PCR matched
      those obtained by IHC. P450 aromatase immunoreaction was restricted to the
      cytoplasm of Leydig cells. These findings suggest that testicular ER may be
      important factors contributing to onset and maintenance of spermatogenesis in the
      boar.

PMID- 15943698
TI  - Validation and usefulness of the Sperm Quality Analyzer (SQA II-C) for bull semen
      analysis.
AB  - In this study, an upgrade version of the Sperm Quality Analyzer (SQA), the SQA
      IIC was tested for the assessment of bull semen quality. In Expt 1, the device
      showed good repeatability of measurements within and between capillaries, as
      evidenced by the low coefficients of variation (CVs; < 13%) at concentrations
      between 35 and 705 x 10(6) spermatozoa/ml. In Expt 2, 10 semen concentrations (1
      1000 x 10(6)/ml) were stored in HEPES TALP for 48 h at room temperature. A time
      dependent decrease in sperm motility index (SMI) values was noticed. SMI values
      increased linearly with increasing sperm concentrations, but remained constant
      around 500, corresponding to a concentration of approximately 50 x 10(6)/ml. For
      sperm concentrations below 50 x 10(6)/ml, SMI values were highly correlated with
      concentration (p < 0.05) and with semen parameters, expressing the overall semen
      quality (p < 0.05; Expt 3). In Expt 4, a correlation of only 0.44 (p < 0.05)
      between SMI values of frozen-thawed semen samples of 35 bulls and the corrected
      56-day non-return rate (56dNRRc) was found. Prediction of the 56dNRRc based on
      the SMI value of a semen sample was inaccurate. The present study indicates that
      the SQA-IIC is suitable for a rapid screening of bull semen diluted to a
      concentration of approximately 50 x 10(6)/ml. Furthermore, the device seems
      inappropriate for fertility prediction.

PMID- 15943699
TI  - In Vitro and in vivo developmental competence of dromedary (Camelus dromedarius)
      embryos produced in vitro using two culture systems (mKSOMaa and oviductal
      cells).
AB  - Development competence and pregnancy rate of in vitro-produced (IVP) dromedary
      embryos were studied in two culture systems: (i) semi-defined modified medium
      (mKSOMaa) and (ii) co-culture using camel epithelial oviducal cells. Five hundred
      and three cumulus-oocytes complexes (COCs) were selected, allowed to mature,
      fertilized and cultured in vitro (38.5 degrees C; 5% CO2, maximum humidity > 95%,
      with concentration of oxygen of 5% for semi-defined medium and 20% for co-culture
      cells). Maturation was accomplished by incubation in TCM-199 medium supplemented
      with 10% heat-treated foetal calf serum (FCS), 10 ng/ml epidermal growth factor,
      1 microg/ml follicle-stimulating hormone, 1 microg/ml oestradiol and 500 microM
      cysteamine for 30 h. In vitro fertilization (IVF) was performed using fresh semen
      (0.5 x 10(6) spermatozoa/ml in modified TALP solution). Fertilized COCs were
      denuded by vortexing, then cultured in either mKSOMaa (10% heat-treated FCS was
      added 24 h post-IVF), under 5% O2 and 90% N2 (group 1; n = 249) or with dromedary
      epithelial oviducal cell monolayers in TCM-199 with 10% heat-treated FCS under
      20% O2 (group 2; n = 254). The rate of cleavage was significant higher (p < 0.05)
      for group 1 (63%, 156/249) than for group 2 (51%, 130/254). No significant
      difference was found between the two groups in the rate of development to
      blastocyst (21% vs 16.5%) and their hatchability (21% vs 14%). Pregnancy rates
      were similar for the first 60 days. However, all pregnancies were lost after 60
      days with the exception of two of six (33%) from recipients of hatched
      blastocysts from group 1. We conclude that both systems support in vitro
      production of dromedary embryos by in vitro maturation (IVM)/IVF of oocytes.
      However, embryos obtained by culture in the semi-defined medium (mKSOMaa) appear
      to have a better in vivo development ability.

PMID- 15943700
TI  - The use of an open-freezing system with self-seeding for cryopreservation of
      mouse ovarian tissue.
AB  - Chemoradiotherapy in young women with cancer has substantially improved life
      expectancy in these patients, but these treatments often cause infertility. One
      method of preserving fertility is to cryopreserve ovarian tissue. In this study,
      an automatic open-vessel freezing system with self-seeding was tested for
      cryopreservation of murine ovarian tissue; the mouse is a species widely used in
      human and veterinary medical research. The freezing system concerned, is used for
      cryopreservation of oocytes and embryos in Europe. Twenty severe combined
      immunodeficiency (SCID) mice were ovariectomized. The ovarian tissue was either
      directly transplanted heterotopically into the neck muscle (group 1, n = 6) or
      cryopreserved after equilibration with 1.5 M dimethylsulphoxide and propanediol.
      After thawing, the tissue was transplanted in SCID mice (group 2, n = 6). Before
      and after thawing, a part of the ovarian tissue was examined with the LIVE/DEAD
      fluorescent viability staining. The count of follicles revealed intact (fresh
      24.1%/thawed 21.7%), impaired (fresh 35.1%/thawed 35.4%), and dead follicles
      (fresh 40.8%/thawed 42.9%). The healthy follicular loss because of the
      cryopreservation was 10.0%. All recipient mice were killed after 3 weeks.
      Transplanted ovarian tissue was found macroscopically in all mice. Histological
      examination showed several growing follicles in all developmental phases in both
      groups of SCID mice [group 1 (fresh grafts): 315 +/- 76.3 (mean +/- SD); group 2
      (cryopreserved grafts): 237 +/- 63.4]. These results demonstrate that the use of
      an open-freezing system allows the survival of cryopreserved mouse ovarian
      tissue.

PMID- 15943701
TI  - Clinical effectiveness of processed and unprocessed bone.
AB  - Bone allografts have been used clinically for a number of years. Understanding
      the biology of bone healing and the impact that bone banking has on this helps to
      improve the methodologies used in increasing the quality and safety of banked
      bone. Banked bone in its various forms has been used in a variety of surgical
      procedures, and although there is no doubt that it is clinically effective, most
      of the studies have been retrospective and non-randomized. The review attempts to
      summarize some of the data in this area and highlights some of the difficulties
      encountered in such work. Although there is no doubt that bone banking is
      nowadays better controlled, there are ever-increasing pressures to produce bone
      that is as safe as possible with the least impact on its effectiveness. This can
      only be achieved if the requirements of the providers and users of bone are
      better understood.

PMID- 15943702
TI  - Use of a solid-phase fluorescent cytometric technique for the detection of
      bacteria in platelet concentrates.
AB  - Blood services worldwide are now striving to reduce the risk of transmission of
      bacteria by transfusion. The BacT/ALERT microbial detection system (bioMerieux,
      Basingstoke, Hants, UK) is currently regarded as the 'gold standard' for
      bacterial screening of platelet concentrates. The BacT/ALERT is a culture system
      and will not generate an 'instant' (within 2 h) determination. We report on the
      Scansystem (Hemosystem, Marseille, France), a solid-phase fluorescent cytometric
      technique, which enables the rapid detection of bacteria (within 90 min) in
      platelet concentrates. The study was performed in two parts - one involving the
      routine screening of platelet concentrates and the other determining the
      sensitivity of the system. In both arms of the study, the BacT/ALERT was used for
      comparative purposes. In total, 900 platelet concentrates were screened (63
      apheresis and 837 buffy coat pooled). No bacteria were detected in any of the
      platelet concentrates tested by means of either the Scansystem or the BacT/ALERT.
      The sensitivity of the Scansystem was in the order of 10(3) cfu mL(-1).
      Escherichia coli and Staphylococcus aureus were detected by using the Scansystem
      at 1 cfu mL(-1). The BacT/ALERT detected all organisms tested (n = 6) at 1 cfu
      mL(-1). The Scansystem offers a sensitive alternative technology to bacterial
      culture, with the benefit of a rapid test time.

PMID- 15943703
TI  - Feasibility of implementing an automated culture system for bacteria screening in
      platelets in the blood bank routine.
AB  - Bacterial contamination of blood components is the principal infectious
      complication linked to transfusion. The aim of the study was to evaluate the
      applicability of an automated culture system for platelets. 10 141 platelet
      concentrates were cultured individually and in pools of five on storage days 1
      and 7 using Bact/Alert system aerobic bottles. A modified collection bag was used
      for improved sampling. Five-millilitre samples were cultured at 37 degrees C for
      7 days. Only those samples where the same bacteria were identified in reculture
      were considered true positives (TP). Homogeneity of proportions was tested by
      Fisher's exact test. The rate of TP was 30 per 100 000 (95% CI, 6.1-86.4)
      sampling on day 1; 33 per 100 000 (95% CI, 7-96) on day 7; and 40 per 100 000
      (95% CI, 1.28-122.4) if the screening was based on taking both samples (day 1 and
      7). Only one TP was detected in the pool testing. The time for detection among
      TPs on day 1 ranged between 30 and 134 h. The system is not considered practical
      for use as a routine screening method, as the time for detection is too long.
      Pool testing is insensitive. Faster screening methods or pathogen-inactivation
      systems are needed.

PMID- 15943704
TI  - Genetic risk factors associated with Creutzfeld-Jakob disease in Slovenians and a
      rapid typing for PRNP codon 129 single nucleotide polymorphism.
AB  - PRNP has been the most informative marker for the predisposition to variant
      Creutzfeld-Jakob disease (vCJD). All victims of the vCJD carried methionine (M)
      at the position 129 of the PrP. Prions could travel through the immune system to
      get from the gut to the brain, and human leucocyte antigens (HLAs) could be
      involved in this carriage, with HLA-DQ7 being less efficient. Contradictory
      reports have raised the question of the influence of sampling in population
      studies. We developed a fast and reliable real-time polymerase chain reaction for
      codon 129 single nucleotide polymorphism (SNP) using TaqMan technology, which
      overcomes the main drawbacks of other methods and analysed Slovenian population
      (n = 97). The comparison with other populations served for the estimation of the
      genetic risk for the development of vCJD in Slovenians. The frequencies at the
      codon 129 SNP in the Slovenian population were 43.3% M, 45.4% M/V 11.3% V.
      Considerable differences between the DQ7 frequencies in diverse samples from the
      same population can be seen, especially when compared to Slovenian population.
      This could be because of the diverse criteria for including subjects into the
      study and the sampling of geographically distinct subpopulations. Analysing the
      adequacy of HLA-DQ7 as a possible predictive factor for developing Creutzfeld
      Jakob disease (CJD) by case - control studies could be improved with exact and
      equal sampling of groups of patients and controls. CJD genetic risk factors in
      the Slovenians were not found significantly different than those in British.

PMID- 15943705
TI  - Cost-effectiveness of leucocyte-depleted erythrocyte transfusion in cardiac valve
      surgery.
AB  - Cost-effectiveness of leucodepleted erythrocytes (LD) over buffy-coat-depleted
      packed cells (PC) is estimated from the primary dataset of a recently reported
      randomized clinical trial involving valve surgery (+/-CABG) patients. Data on the
      patient level of 474 adult patients who were randomized double-blind to LD or PC
      were used in order to calculate the healthcare costs and longevity per patient.
      The incremental cost-effectiveness ratio (ICER) in net costs per life-year gained
      was established from the healthcare perspective. Bootstrapping and cost
      effectiveness acceptability curves were used in order to determine the confidence
      interval (CI) of the ICER. The longevity of patients in the PC and LD group was
      10.6 and 11.4 years, respectively. Relative to PC, LD yielded an estimated 0.8
      (95% CI = -0.27 to 1.84) life-year in the baseline. Adjusted for age and sex
      differences, health gains for LD are 0.4 life-year gained (95% CI = -0.67 to
      1.44). Healthcare costs per patient averaged 10163 US dollars per patient in the
      PC group and 9949 US dollars in the LD group. Average cost-savings were 214 US
      dollars (95% CI = -1536 to 1964) per patient. Acceptability curves constructed
      from bootstrap simulations showed a probability of being cost-saving of 59% for
      universal leucodepletion from the healthcare perspective. The probability of
      adopting leucodepletion regardless of the costs reaches 92.7%. LD in patients
      receiving four or more transfusions showed the highest cost-savings and health
      gains. Leucodepletion of erythrocytes is a cost-saving strategy in cardiac valve
      (+/-CABG) patients. However, probablistic analysis failed to show a significant
      difference with buffy-coat-depleted PC.

PMID- 15943706
TI  - Home blood transfusion: a necessary service development.
AB  - An alternative to the transfusion of blood and platelets in hospital was assessed
      with the aim of reducing the demand on acute services and the need for hospital
      admission. Patients and general practitioners [GPs] were surveyed before a home
      blood transfusion service was set up. The majority of GPs and patients did not
      support the scheme initially. After the service was set up, all patients who
      received home transfusion stated that this was more convenient. We feel that by
      avoiding unnecessary emergency admissions, which account for up to 40% of all
      admissions to NHS hospitals, and improving the capacity of our day unit, we are
      providing a better service for local patients. More widespread use of home
      transfusion services should be encouraged.

PMID- 15943707
TI  - Storage of neutrophil granulocytes (PMNs) in additive solution or in autologous
      plasma for 72 h.
AB  - Neutropenia may necessitate polymorphonuclear (PMN) transfusion, but among other
      reasons, PMN short shelf-life complicates realization of innovative transfusion
      strategies. In 18 donors, PMNs were mobilized using rHuG-CSF + dexamethasone.
      (8.3 +/- 1.6) x 10(10) PMNs were harvested in 203 +/- 8.7 mL. PMNs were stored
      undiluted (1, n = 18) and diluted 1-in-2, 1-in-4, 1-in-8 using T-Sol (2, n = 6),
      T-Sol + 1% HSA (3, n = 6), or autologous plasma (4, n = 6) for 72 h. Haemograms,
      pH values, phagocytosis, oxidative burst, and interleukin (IL)-1beta, IL-8 and
      tumour necrosis factor (TNF)-alpha levels were assessed every 24 h. PMN count
      decreased from (4.3 +/- 0.8) x 10(10) to (2.2 +/- 1.0) x 10(10), and pH value
      dropped from 6.4 +/- 0.3 to 5.4 +/- 0.2 within 72 h (1), whereas 1-in-4 and 1-in
      8 dilutions exhibited consistent haemograms and pH values above 6.0. 1-in-8
      dilution (4) stabilized pH at 7.1 +/- 0.4 after 72 h. Function deteriorated to
      about 50% within 24 h (1), but 1-in-8 (3), 1-in-4 and 1-in-8 diluted PMNs (4)
      kept it >90% for 72 h. In all collectives, cytokine levels increased during
      storage. After all, IL-1beta ranged between 31.0 +/- 16.3 (1-in-4, 4) and 100.0
      +/- 21.4 (1-in-4, 2), IL-8 from 513 +/- 454 (1) to 3180 +/- 760 (1-in-8, 2), and
      TNF-alpha between 3.8 +/- 1.7 (1-in-2, 2) and 23.2 +/- 11.8 (1-in-8, 4) (pg mL(
      1)). PMN function may be preserved for 72 h in vitro by dilution of PMN
      apheresates with, preferably, autologous plasma.

PMID- 15943708
TI  - Calcium and magnesium levels during automated plateletpheresis in normal donors.
AB  - It is well known that citrate induces ionized hypocalcaemia by the chelating
      effect during plateletpheresis. However, the kinetics of serum magnesium (Mg)
      ions has not been well documented. We, therefore, evaluated biochemical changes
      in healthy donors during plateletpheresis procedure. Ten healthy donors underwent
      plateletpheresis on continuous cell separator (CS3000, Baxter, Round Lake, IL,
      USA) and 10 on intermittent flow cell separator (MCS 3p, Hemonetics, Braintree,
      MA, USA). Serum levels of total and ionized calcium (tCa and iCa, respectively)
      and Mg (tMg and iMg, respectively) were measured before, during and after the
      procedures. Although, the fall in tCa (from 2.62 +/- 0.12 to 2.36 +/- 0.12 mmol
      L(-1)) and tMg (from 0.89 +/- 0.01 to 0.79 +/- 0.01 mmol L(-1)) was modest and
      not significant; drop in iCa (from 1.33 +/- 0.1 to 0.84 +/- 0.1 mmol L(-1)) and
      iMg (from 0.53 +/- 0.01 to 0.35 +/- 0.1 mmol L(-1)) was statistically significant
      (P < 0.001). There were no significant differences observed between the CS3000
      and MCS 3p cell separators regarding the fall in Ca and Mg. None of the donors
      experienced any adverse reactions during the procedures. In the study, an acute
      ionized hypocalcaemia and hypomagnesaemia have been observed after the
      plateletpheresis; therefore, measurement of both the ions may be monitored.
      However, there is no justification for prophylactic supplementation of either of
      these elements.

PMID- 15943709
TI  - The Duffy blood groups of Jarawas - the primitive and vanishing tribe of Andaman
      and Nicobar Islands of India.
AB  - Andaman and Nicobar Islands, union territory of India were inhabited by 14
      aboriginal tribes. Some of these tribal populations have already become extinct,
      and the numbers of the existing ones are also dwindling. This group of islands
      being highly endemic for malaria, it was considered worthwhile to study the
      hunter-gatherer primitive tribe, Jarawas, for their Duffy blood group phenotype.
      Jarawas, the primitive tribe of Andaman Islands, inhabit the three jungle areas
      of South and one jungle area of Middle Andaman. Blood samples of 116 Jarawas were
      collected and tested for Duffy blood group and malarial parasite infectivity. The
      Duffy blood grouping was performed as per standard serological techniques, and
      peripheral smears were screened for malarial parasite and if present parasite
      density count was performed and the species identified. The results showed a
      total absence of both Fy(a) and Fy(b) antigens in two areas (Kadamtala and R.K.
      Nallah) and low prevalence of Fy(a) antigen in another two areas (Jirkatang and
      Tirur). There was absence of malarial parasite Plasmodium vivax infection though
      Plasmodium falciparum infection was present in 27.59% of cases. A very high
      frequency of Fy (a-b-) in the Jarawa tribe from all the four jungle areas of
      Andaman Islands along with total absence of P. vivax infections suggests the
      selective advantage offered to Fy (a-b-) individuals against P vivax infection.

PMID- 15943710
TI  - Pseudocontamination of blood components with Burkholderia cepacia during quality
      controls.
AB  - We report on a pseudooutbreak of Burkholderia cepacia because of the use of a
      contaminated disinfectant during quality controls in a university blood bank. No
      septic reactions associated with transfusions had been reported in patients over
      the last 6 months. Analysis of the individual quality control procedures showed
      that a disinfectant based on a quaternary ammonium compound (QAC) had been used
      in order to disinfect the rubber stopper of the blood culture bottle. B. cepacia
      was found in a sample taken from this disinfectant, which was prepared with
      concentrate and tap water according to the manufacturer's instructions. The four
      isolates (one in disinfectant and three in blood components) were found to be
      identical in their biochemical reactions and resistance patterns. QAC-based
      disinfectants are not efficacious against a part of the spectrum of gram
      negatives and are therefore inadequate. After introduction of an alcohol-based
      preparation, no more cases of B. cepacia contamination have been identified.

PMID- 15943711
TI  - Anti-HPA-1a in a case of post-transfusion purpura: binding to antigen-negative
      platelets detected by adsorption/elution.
AB  - Post-transfusion purpura (PTP) is a rare transfusion reaction almost exclusively
      observed in female patients. Affected patients develop severe immune-mediated
      thrombocytopenia in the course of a strong anamnestic alloimmune reaction against
      a platelet-specific antigen. The pathophysiology of thrombocytopenia has remained
      elusive. Immunological analysis in the HPA-1a-alloimmunized patient described in
      this report revealed an antibody with features considered typical of PTP: not
      only was anti-HPA-1a detectable in plasma, but it could also be eluted from the
      patients' (alloantigen negative) platelets, and anti-HPA-1a could be detected in
      eluates from both antigen positive and negative test platelets, which had been
      incubated in the patient's serum. This is in contrast to two sera with HPA-1a
      alloantibodies obtained from mothers of children with neonatal alloimmmune
      thrombocytopenia which were strictly HPA-1a specific. It is proposed that
      alloantibodies with HPA-1a-like specificity explain the patient's immune
      thrombocytopenia. The technique described in this report is proposed for further
      investigation, as it might be useful for discrimination of alloantibodes in PTP
      and alloantibodies of transfused thrombocytopenic patients.

PMID- 15943712
TI  - First HIV 'window period' donation in a UK blood donor.

PMID- 15943713
TI  - Nucleic acid amplification technology screening for HBV DNA in Italy: routine
      application. Report on the first HBV DNA-positive HBsAG-negative donor.

PMID- 15943714
TI  - Paroxysmal cold haemoglobinuria/Donath-Landsteiner test.

PMID- 15943715
TI  - Systematic review of autologous transfusion techniques.

PMID- 15943718
TI  - Future of magnetic resonance imaging and magnetic resonance spectroscopy in
      oncology.

PMID- 15943719
TI  - 3-D magnetic resonance angiography versus conventional angiography in peripheral
      arterial disease: pilot study.
AB  - BACKGROUND: Angiography is usually performed as the preoperative road map for
      those requiring revascularization for lower extremity peripheral arterial disease
      (PAD). The alternative investigations are ultrasound, 3-D magnetic resonance
      angiography (3-D MRA) and computed tomography angiography. This pilot study aimed
      to assess whether 3-D MRA could replace the gold standard angiography in
      preoperative planning. METHODS: Eight patients considered for aortoiliac or
      infrainguinal arterial bypass surgery were recruited. All underwent both imaging
      modalities within 7 days. A vascular surgeon and a radiologist each reported on
      the images from both the 3-D MRA and the angiography, with blinding to patient
      details and each others reports. Comparisons were made between the reports for
      the angiographic and the 3-D MRA images, and between the reports of the vascular
      surgeon and the radiologist. RESULTS: Compared to the gold standard angiogram, 3
      D MRA had a sensitivity of 77% and specificity of 94% in detecting occlusion, and
      a sensitivity of 72% and specificity of 90% in differentiating high grade (>50%)
      versus low grade (<50%) stenoses. There was an overall concordance of 78% between
      the two investigations with a range of 62% in the peroneal artery to 94% in the
      aorta. 3-D MRA showed flow in 23% of cases where conventional angiography showed
      no flow. CONCLUSIONS: In the present pilot study, 3-D MRA had reasonable
      concordance with the gold standard angiography, depending on the level of the
      lesion. At times it showed vessel flow where occlusion was shown on conventional
      angiogram. 3-D MRA in peripheral vascular disease is challenging the gold
      standard, but is inconsistent at present.

PMID- 15943720
TI  - Prospective comparison of routine and selective operative cholangiography.
AB  - BACKGROUND: In a rural centre with limited resources and no endoscopic retrograde
      cholangiopancreatography facilities, a prospective cohort study was established
      to compare policies of routine and selective intraoperative cholangiography (IOC)
      in order to develop a local protocol. METHODS: Patients undergoing laparoscopic
      cholecystectomy from 1 February 1995 to 30 November 2002 were allocated to
      undergo routine or selective IOC according to birth date. Those with known common
      bile duct (CBD) stones were excluded. Selective IOC was performed on the basis of
      abnormal liver function tests or a dilated CBD on ultrasound. Study end points
      after 12 months follow-up were retained CBD stones, CBD injury, operating times
      and the effect of IOC on the management of patients with persistent biliary
      symptoms postoperatively. RESULTS: Of the 148 patients in the routine group, 94
      underwent IOC and CBD stones were shown in 12. Of the 155 in the selective group,
      IOC was performed in 34 of 45 eligible patients and stones were shown in five.
      Sixteen patients re-presented with recurrent biliary symptoms or jaundice
      postoperatively and eight had proven retained CBD stones, of whom only one had
      undergone (false-negative) IOC. There was no significant difference in mean
      operating time (56 vs 61 min; t-test P = 0.15). There was one CBD injury in each
      group, both incurred after successful IOC. CONCLUSIONS: There was no difference
      between policies of routine or selective IOC in relation to operating times,
      retained CBD stone rates or CBD injury. However, the authors found management of
      patients with recurrent biliary symptoms easier if an IOC had been performed, and
      IOC was easier to perform when the staff were expecting it. Thus a policy of
      routine IOC has been adopted.

PMID- 15943721
TI  - Repair of injuries to the thoracic aorta and great vessels: Auckland, New Zealand
      1995-2004.
AB  - BACKGROUND: Traumatic injury to the aorta and great vessels is a surgical
      emergency with survivors who reach hospital typically having suffered multiple
      injuries. There are several diagnostic and treatment options available, with new
      modalities emerging to challenge the gold standards. A review of recent trends in
      management of these injuries in Auckland, New Zealand was carried out and patient
      outcomes assessed. METHODS: The charts of patients admitted to Auckland and Green
      Lane Hospital's cardiothoracic intensive care unit, with a diagnosis of injury to
      the thoracic aorta or great vessels since 1995 were retrospectively reviewed.
      Imaging techniques, injury types and treatment methods were analysed along with
      survival and neurological morbidity. RESULTS: In the study period our unit
      operated on 29 cases of traumatic rupture of the thoracic aorta or great vessels.
      Digital subtraction angiography and more recently, multidetector computed
      tomography scanning have been used to diagnose the injury. Twenty-seven injuries
      were to the aorta and two to the innominate artery. The 30-day survival rate of
      those reaching the operating theatre was 90%. There was one case of postoperative
      hemiparesis and five cases of recurrent laryngeal nerve injury, but none of
      spinal cord ischaemic injury. Endoluminal stent grafting was carried out for one
      patient, without complication. CONCLUSIONS: Good survival rates exist for those
      who reach surgery for traumatic rupture of the aorta or great vessels.
      Multidetector computed tomography scanning is an alternative to digital
      subtraction angiography, potentially reducing treatment delay. In addition
      endoluminal grafting as opposed to open repair has been reported as a safe
      technique. The injury remains a surgical emergency requiring urgent diagnosis and
      transfer to an equipped cardiothoracic unit for definitive treatment.

PMID- 15943722
TI  - Is temporal artery biopsy a worthwhile procedure?
AB  - BACKGROUND: Temporal artery biopsy (TAB) has been accepted as the gold standard
      for the diagnosis of giant cell arteritis (GCA) or temporal arteritis (TA) even
      though it is of low sensitivity and specificity. Current medical practice
      recommends commencing high dose steroids before performing a biopsy, and the
      continued use of long-term steroids even if biopsy is negative but clinical
      suspicion of the diagnosis is high. The aim of the present study is to determine
      if TAB results actually changes the management of patients suspected of GCA or
      TA. METHODS: Retrospective case note analysis of 70 consecutive patients with TAB
      over 5 years (1999-2003) from Royal Melbourne Hospital (RMH), Melbourne,
      Australia. RESULTS: Histology revealed five (7%) positive biopsies, five (7%) of
      'healed arteritis', and 60 (86%) negative biopsies. After excluding 15 patients
      who were lost to follow up, management of 13 (23.6%) patients was influenced by
      the biopsy results: seven with negative biopsies had steroids discontinued while
      six patients with biopsies showing positive and healed arteritis continued on
      steroids. Management of 42 (76.4%) patients was not altered following biopsy
      results: 11 with negative biopsy continued on steroids, 19 never started because
      of low clinical suspicion and 12 ceased steroids some time after biopsy as there
      was no symptomatic improvement. CONCLUSION: With the management of 76.4% of
      patients unchanged following biopsy, some may argue that these patients underwent
      unnecessary surgery. However, TAB is a minor procedure that can yield important
      results for the management of GCA, which if untreated can lead to serious
      complications. We believe TAB should be performed where there is clinical
      suspicion of GCA.

PMID- 15943723
TI  - Extrahepatic biliary anatomy at laparoscopic cholecystectomy: is aberrant anatomy
      important?
AB  - BACKGROUND: The prevention of major duct injury at cholecystectomy relies on the
      accurate dissection of the cystic duct and artery, and avoidance of major
      adjacent biliary and vascular structures. Innumerable variations in the anatomy
      of the extrahepatic biliary tree and associated vasculature have been reported
      from radiographical and anatomical studies, and are cited as a potential cause of
      bile duct injury at cholecystectomy. METHODS: A photographic study of the
      dissected anatomy of 186 consecutive cholecystectomies was undertaken and each
      photo analysed to assess the position of the cystic duct and artery, the common
      bile duct and any anomalous structures. RESULTS: The anatomy in the region of the
      gallbladder neck was relatively constant. Anatomical variations were uncommon and
      anomalous ducts were not seen. Vascular variations were the only significant
      abnormalities found in the present series. CONCLUSION: Anatomy in the region of
      the gallbladder neck varies mostly in vascular patterns. Aberrant ducts or duct
      abnormalities are rarely seen during cholecystectomy hightlighting the principle
      that careful dissection and identification is the key to safe cholecystectomy.

PMID- 15943724
TI  - Percutaneous cholecystostomy in the management of acute cholecystitis.
AB  - BACKGROUND: Percutaneous cholecystostomy (PC) has been used in managing acute
      cholecystitis in the setting of a patient with severe comorbidities where
      emergency cholecystectomy would carry significant mortality. The present study
      aims to assess the role, efficacy and complications of PC in acute cholecystitis.
      METHODS: Retrospective review of case notes of patients who underwent PC at Box
      Hill Hospital, Melbourne, Australia between July 1997 and December 2002. RESULTS:
      Sixteen patients (mean age 75 years; range 50-96) underwent PC. Indications for
      PC were significant comorbidities (n = 6), failure of conservative treatment (n =
      4), bile duct malignancy (n = 2), sepsis of unknown origin (n = 2), patient
      declined surgery (n = 1) and local perforation (n = 1). Technical success rate
      was 94%. Clinical response to PC was observed in 15 patients. Overall mortality
      was 18% (3/16) with one death caused by PC failure. Interval cholecystectomy was
      performed in seven patients (44%). CONCLUSIONS: Percutaneous cholecystostomy is a
      useful alternative means of treating non-resolving acute cholecystitis in
      circumstances where emergency surgery is hazardous. It also offers effective
      palliation in patients not suitable for subsequent surgery.

PMID- 15943725
TI  - Should serum pancreatic lipase replace serum amylase as a biomarker of acute
      pancreatitis?
AB  - BACKGROUND: Serum pancreatic lipase may improve the diagnosis of pancreatitis
      compared to serum amylase. Both enzymes have been measured simultaneously at our
      hospital allowing for a comparison of their diagnostic accuracy. METHODS:
      Seventeen thousand five hundred and thirty-one measurements of either serum
      amylase and or serum pancreatic lipase were made on 10 931 patients treated at a
      metropolitan teaching hospital between January 2001 and May 2003. Of these, 8937
      were initially treated in the Emergency Department. These results were collected
      in a database, which was linked by the patients' medical record number to the
      radiology and medical records. Patients with either an elevated lipase value or a
      discharge diagnosis of acute pancreatitis had their radiological diagnosis
      reviewed along with their biochemistry and histology record. The diagnosis of
      acute pancreatitis was made if there was radiological evidence of peripancreatic
      inflammation. RESULTS: One thousand eight hundred and twenty-five patients had
      either elevated serum amylase and or serum pancreatic lipase. The medical records
      coded for pancreatitis in a further 55 whose enzymes were not elevated. Three
      hundred and twenty of these had radiological evidence of acute pancreatitis.
      Receiver operator characteristic analysis of the initial sample from patients
      received in the Emergency Department showed improved diagnostic accuracy for
      serum pancreatic lipase (area under the curve (AUC) 0.948) compared with serum
      amylase (AUC, 0.906, P < 0.05). A clinically useful cut-off point would be at the
      diagnostic threshold; 208 U/L (normal <190 U/L) for serum pancreatic lipase and
      114 U/L (normal 27-100 U/L) for serum amylase where the sensitivity was 90.3 cf.,
      76.8% and the specificity was 93 cf., 92.6%. 18.8% of the acute pancreatitis
      patients did not have elevated serum amylase while only 2.9% did not have
      elevated serum pancreatic lipase on the first emergency department measurement.
      CONCLUSION: It is concluded that serum pancreatic lipase is a more accurate
      biomarker of acute pancreatitis than serum amylase.

PMID- 15943726
TI  - Effect of total knee arthroplasty on recreational and sporting activity.
AB  - BACKGROUND: Common concerns of patients undergoing total knee arthroplasty (TKA)
      are whether they can continue with certain recreational and sporting activities
      or even commence new ones after the procedure. The present study was designed to
      determine preoperative and postoperative activities, the numbers participating
      and the time to resume these activities. METHODS: Between 1 and 2 years after
      TKA, patients who had undergone 144 arthroplasties, were surveyed by postal
      questionnaire to ascertain how the arthroplasty had affected their recreational
      and sporting ability. Their preoperative and postoperative activity along with
      the time to resume was recorded. The Oxford knee score and estimate of physical
      activity was also collected. RESULTS: Out of the 144 TKA performed, 122
      participated in sport and recreational activity preoperatively and 108
      participated postoperatively. Patients stated that the surgery had a beneficial
      effect on their performance of sporting and recreational activities although the
      number of sporting events decreased. By multiplying individuals by the number of
      activities they participated in, there were 254 occurrences of sport and
      recreational activities preoperatively giving a mean for the group of 1.76
      sports/patient. Postoperatively this had reduced to 204, giving a mean of 1.41.
      Three activities showed a significant change for individual patients from pre- to
      postoperation. Those which showed an increase were exercise walking, where 19
      patients (13.2%) who did not walk before surgery took up walking afterwards (P <
      0.006) and aqua aerobics, where five took up aqua aerobics postoperatively for
      the first time (P < 0.025). Golf was the only sport which had a significant fall
      in participation from pre- to postoperation, with 10 out of 19 golfers giving up
      (P < 0.025). CONCLUSION: The present study has shown that patients are adopting
      lower impact activities to participate in after TKA. The total number of patients
      performing a sport decreases postoperatively and the total amount of sport played
      decreases. These data will help to counsel patients.

PMID- 15943727
TI  - Steroid-induced avascular necrosis of the hip in neurosurgical patients:
      epidemiological study.
AB  - BACKGROUND: Avascular necrosis (AVN) of the femoral head is perceived to be a
      rare complication of short-term steroid therapy for neurosurgical conditions but
      its precise risk is unknown. METHODS: Retrospective review of hospital records
      between 1994 and 2001. RESULTS: The risk of developing AVN of the femoral head is
      0.3% with an incidence of one per one thousand patients per year. CONCLUSIONS: It
      would be advisable to minimize both the dosage and the duration of steroid
      treatment where possible.

PMID- 15943728
TI  - Transfer of facially injured road trauma victims and its impact on treatment.
AB  - BACKGROUND: Road trauma is a common cause of severe facial injuries. The aim of
      the present study is to define patients involved, and determine the effect of
      their geographical origin on treatment and follow up. METHODS: All patients over
      14 years of age suffering facial injuries caused by road trauma presenting to the
      two study hospitals from 1994 to 1999 were identified and details were collected
      on demographic details and treatment. RESULTS: Four hundred and nine patients met
      the inclusion criteria. The majority required hospital transfer. Young men were
      the most frequently injured group of patients. Patients from peripheral regions
      had significant delays in transfer and treatment. They were made fewer outpatient
      appointments but attended at the same frequency as patients from the immediate
      region of the study hospitals. CONCLUSIONS: To minimize delays the process of
      patient transfer needs to be streamlined and education of staff in peripheral
      hospitals undertaken regarding facial injuries.

PMID- 15943729
TI  - Clinical diagnosis of skin tumours: how good are we?
AB  - BACKGROUND: Few studies have addressed the accuracy of clinical diagnosis of skin
      malignancies. The present prospective study aims to determine the accuracy with
      which these lesions are diagnosed and attempts to identify the factors
      influencing the accuracy of clinical diagnosis. METHODS: All patients undergoing
      surgical excision of a skin cancer with curative intent from January 2001 to
      December 2002 at Peter MacCallum Cancer Institute, Melbourne, Australia were
      prospectively studied. Data were entered into the Filemaker Pro program and
      analysed using the SPSS software package. RESULTS: A total of 2582 lesions were
      surgically excised from 1223 patients. Of these 47% were basal cell carcinomas
      (BCC), 20% were squamous cell carcinomas (SCC), 0.9% were malignant melanomas
      (MM), and 32.1% were benign or premalignant. Tumours, benign and malignant, were
      found to be more common in men. The sensitivity for clinical diagnosis of
      malignancy was 97.5% while the positive predictive value (PPV) for clinical
      diagnosis of malignancy was 70.3%. BCC and SCC was diagnosed with a sensitivity
      of 89% and 56.3%, and PPV of 64.5% and 40.3%, respectively (P < 0.001). 23 MM
      were excised with a sensitivity of clinical diagnosis of 47.8% and PPV of 30.6%.
      Sensitivity and PPV were also assessed according to clinical experience of the
      surgeon, site of the lesion and whether surgery was performed for a primary or a
      recurrent lesion. Sensitivity and PPV were higher for lesions diagnosed by
      consultant surgeons when compared with surgical trainees (P < 0.001) - MM was
      diagnosed with a sensitivity of 100% by consultant surgeons. CONCLUSION: The
      present study shows sensitivity and PPV rates comparable to published figures.

PMID- 15943730
TI  - The learning curve in learning the curve: a review of Nuss procedure in
      teenagers.
AB  - BACKGROUND: The Nuss procedure is a new minimally invasive repair for pectus
      excavatum that was first published in 1998. Modifications in technique are
      constantly evolving to minimize complications, especially bar displacement, which
      are higher in adolescents and adults. The present study reviews our early
      experience with this procedure in a much older group of children than previously
      reported and suggests an alternative method of avoiding bar displacement.
      METHODS: Retrospective chart review was carried out on 78 consecutive patients
      who underwent the Nuss procedure between December 1999 and January 2004. All
      patients underwent a uniform technique using bilateral lateral stabilisers and
      thoracoscopy was not used. Operative details, subjective cosmetic results and
      complication rates were assessed. RESULTS: The mean age was 15.4 +/- 3.2 years.
      Single bars were used in 95%, double bars in 5%. The defect was asymmetrical in
      26%. The defect was mild in 7%, moderate in 59% and severe in 34%. The median
      length of stay was 6.0 days (range 4-11). Total operating time was 58 min (range
      35-95). Patient controlled analgesia (morphine) for pain relief was used for 105
      h (range 61-169) or 4.4 days; the epidural infusion was stopped 1 day earlier.
      Cosmetic results were excellent in 80.3%. There was residual asymmetry in 75% of
      the asymmetrical defects although all were improved. Complications included eight
      (10%) reoperations for bar displacement. This was related to the learning curve
      as seven of these occurred in the first 2 years of the series. Removal of the bar
      has been accomplished in 31 (40%) patients. This was elective in all but four
      patients (three early removals for pain and one for infection). CONCLUSIONS: The
      Nuss procedure gives good results even in teenagers. Modification of technique
      and increased experience has reduced complications. The use of bilateral lateral
      stabilisers without additional wire fixation is an alternative method to avoid
      bar displacement.

PMID- 15943731
TI  - Optimum duration of prophylactic antibiotics in acute non-perforated
      appendicitis.
AB  - BACKGROUND: The effect of extended prophylactic antibiotic therapy on
      postoperative infective complications such as wound infection and intra-abdominal
      abscess for non-perforated appendicitis is poorly defined. METHODS: In a
      randomized controlled trial of 269 patients aged 15-70 years with non-perforated
      appendicitis undergoing open appendicectomy; 92 received single dose preoperative
      (group A), 94 received three-dose (group B) and 83 received 5-day perioperative
      (group C) regimens of cefuroxime and metronidazole. Postoperative infective
      complication was the primary endpoint. Secondary outcomes included length of
      hospital stay and complications related to antibiotic therapy. RESULTS: The rate
      of postoperative infective complication was not significantly different among the
      groups (6.5% group A, 6.4% group B, 3.6% group C). The duration of antibiotic
      therapy had no significant effect on the length of hospital stay. Complications
      related to antibiotic treatment were significantly more common for 5-day
      perioperative antibiotic group (C) compared with single dose preoperative
      antibiotic group (A) (P = 0.048). CONCLUSION: Single dose of preoperative
      antibiotics is adequate for prevention of postoperative infective complications
      in patients with non-perforated appendicitis undergoing open appendicectomy.
      Prolonging the use of antibiotics can lead to unnecessary antibiotic related
      complications.

PMID- 15943732
TI  - Outcome and quality of life after cardiac surgery in octogenarians.
AB  - BACKGROUND: Cardiac surgery is being performed with increasing frequency in
      octogenarians. The purpose of the present study was to determine the outcome and
      quality of life of octogenarians after cardiac surgery in a single surgeon series
      and in a newly established cardiac surgery unit. METHODS: Prospective data
      collection and analysis were undertaken of octogenarians having cardiac surgery
      from 1997 to 2003 by a single surgeon in a single institution. The outcome was
      compared to septuagenarians operated on by the same surgeon in the same time
      frame, specifically to see if there were any significant differences in outcomes
      between these two close age groups. Follow up was conducted by sending a
      questionnaire, interviewing patients or their general practitioner. RESULTS:
      There were significantly less octogenarians with airway disease but more with
      class III and IV New York Heart Association heart failure. There were no
      significant differences in the incidence of left main disease, urgent operations,
      renal impairment and cerebrovascular disease between the two groups. There was a
      trend towards increased operative mortality in octogenarians when the group was
      taken as a whole (8%vs 2%, P = 0.052). They also had a significantly higher
      incidence of respiratory failure (6%vs 2%, P = 0.029). The incidence of stroke,
      renal failure and low cardiac output was not significantly different between the
      two groups. Blood product usage was significantly higher in octogenarians (19%vs
      9%, P = 0.042), but re-operation for bleeding was not significantly different
      (3%vs 4%). Intensive care unit median length of stay was significantly longer in
      the case of Octogenarians (1.0 vs 0.9 days, P = 0.039), but the duration of
      hospital stay was similar (6.5 vs 6.4 days, P = 0.165). Follow up was 94.5%
      complete, 85% of the octogenarians responded to the questionnaire sent to them.
      All patients were free of angina, 98% of them had improved by at least one New
      York Heart Association heart failure class and 86.7% felt that they were less
      dependent on others after cardiac surgery. In retrospect, 94.2% said that they
      would have the procedure again. CONCLUSION: Octogenarians can be operated on with
      acceptable mortality and morbidity to achieve significant improvement in quality
      of life. The outcome of surgery in these patients in a new unit is comparable
      with established units.

PMID- 15943733
TI  - Hartmann procedure: is it still relevant today?
AB  - BACKGROUND: With more and more centres worldwide resorting to primary anastomosis
      for most left sided colonic pathology, the place for a Hartmann procedure seems
      to be relegated to surgical history books. However, in our centre it is still
      being performed on a regular basis. As such, we decided to retrospectively look
      at our results for the procedure. METHODS: All hospital records of patients
      undergoing the Hartmann procedure between January 1998 and December 2001 were
      retrospectively analysed looking at demographics, comorbidities and indications
      of the procedure. RESULTS: There were 52 men and 33 women with a median age of 69
      years (range 31-96 years). Sixty-six per cent of the patients had medical
      comorbidities at the time of the operation. The indications for performing the
      procedure were: 45 patients for cancer (31 patients for obstruction, 11 patients
      for perforation, two patients for fistulation to other organs and one for
      uncontrollable bleeding). 19 patients had the procedure for complicated
      diverticulitis while four patients had anastomotic leaks, which required
      conversion to the procedure. Other indications include trauma (four patients),
      ischemic bowel (six patients) and iatrogenic (one patient). Our median operating
      time was 160 min (range 50-415 min). Our reversal rate was 32%. Our mortality
      rate for the first stage was 16% and our morbidity, 51%. The morbidity for the
      reversal was 29%, with no mortalities. CONCLUSION: Though the idea of primary
      anastomosis with on table lavage for left sided anastomosis seems attractive, we
      think the Hartmann procedure is still useful for selected patients.

PMID- 15943734
TI  - Aggressive surgical resection for carcinoma of gallbladder.
AB  - BACKGROUND: The aim of the present study was to review the long-term result of
      patients with carcinoma of gallbladder with adequate investigations and
      aggressive surgical resection. METHODS: A retrospective study was carried out on
      patients with carcinoma of gallbladder treated at the Division of
      Hepatopancreatobiliary Surgery, the Chinese University of Hong Kong from January
      1997 to December 2002. RESULTS: Of the 47 patients with carcinoma of gallbladder,
      28 patients were treated symptomatically because they were found to have
      metastatic disease (n = 22), unresectable disease (n = 2) or poor associated
      medical disease (n = 4). One patient had carcinoma in-situ after laparoscopic
      cholecystectomy. No further treatment was considered necessary. The remaining 18
      patients (38.3%) came to laparotomy after preoperative investigations with
      ultrasonography, computed tomography, endoscopic or percutaneous cholangiography,
      and visceral angiography. Laparoscopy and laparoscopic ultrasound were used in
      the later part of the study. Radical cholecystectomy was carried out in 14
      patients (77.8%). The in-hospital mortality rate was 5.3% and the surgical
      morbidity was 31.6%. The remaining four patients underwent palliative
      cholecystectomy because of the extent of the disease. The overall 5-year survival
      for the 47 patients was 19.1%, for the 18 patients who came to laparotomy was
      44.4%, and for the 14 patients who underwent resection with curative intent was
      57.1%. CONCLUSIONS: With adequate preoperative investigations, and the use of
      laparoscopy and laparoscopic ultrasound, radical resection was possible in the
      majority of patients who came to laparotomy for carcinoma of gallbladder.
      Aggressive radical resection gave good results.

PMID- 15943735
TI  - Qualitative assessment of breast reconstruction in a specialist breast unit.
AB  - BACKGROUND: Breast reconstruction is an integral part of the surgical management
      of women with breast cancer. It is often performed by plastic surgeons but, in
      some centres, it is performed by breast surgeons trained in breast reconstruction
      and oncoplastic surgery. We evaluated the objective and subjective outcomes of
      reconstruction for breast cancer at the Royal Adelaide Hospital Breast Unit
      (Adelaide, Australia) between 1990 and June 2002. METHODS: A chart analysis was
      conducted of all patients who underwent breast cancer reconstruction at the Royal
      Adelaide Hospital Breast Unit with analysis of type of reconstruction and
      complications. Patients were interviewed and self-assessment quality of life
      questionnaires (FACT-B, body image), and overall satisfaction with reconstruction
      using an analogue scale were performed. Three observers carried out photographic
      analysis of the reconstructions. A comparison was then made between the different
      forms of reconstruction used. RESULTS: One hundred and ninety-two patients
      underwent a total of 219 breast reconstructions during this period. The
      reconstructions included 18 latissimus dorsi mini flaps, 83 tissue
      expander/implants, 43 latissimus dorsi flaps and 75 TRAM flaps. There were no
      perioperative deaths. Significant systemic complications occurred in four
      patients (2%). Significant implant related complications occurred in four
      patients (3.2% of patients with implants). Total flap loss occurred in four
      patients (2.9% of flaps). One hundred and twenty-three patients were able to be
      contacted and completed the questionnaires. Overall 77% of patients were highly
      satisfied with breast reconstruction and 82% scored a satisfactory result on
      photographic analysis. All four forms of reconstruction rated highly with respect
      to quality of life, body image, patient satisfaction and photographic assessment.
      CONCLUSIONS: Breast reconstruction undertaken by breast surgeons trained in
      breast reconstruction and oncoplastic techniques has been performed with an
      acceptable rate of complications and a high level of patient satisfaction.
      Satisfaction with breast reconstruction was similar across the four methods of
      reconstruction used.

PMID- 15943736
TI  - Breast reconstruction after mastectomy: current state of the art.

PMID- 15943737
TI  - Magnetic resonance in surgical oncology: I - on the origin of the spectrum.
AB  - The discovery of the phenomenon of nuclear magnetic resonance occurred just 60
      years ago. The profusion of subsequent discoveries in this domain has led to the
      development of magnetic resonance spectroscopy - refined as an analytical tool to
      discern molecular structure - and magnetic resonance imaging, a cornerstone of
      modern radiology. Observable alterations in cellular structure and metabolism can
      be discerned using the non-destructive chemical analysis of magnetic resonance
      spectroscopy in vitro or in vivo. Differences may thus be discerned between
      malignant and normal tissues.

PMID- 15943738
TI  - Magnetic resonance in surgical oncology: II - literature review.
AB  - Ex vivo and in vivo applications of magnetic resonance spectroscopy have been
      developed which aid in distinguishing malignant from normal tissues. Studies of
      breast, colon, cervix, oesophageal and prostate cancer reveal both the successes
      and failings of present technology. Verification that these non-invasive tests
      might supplant conventional histology in obtaining spatial diagnostic and
      chemical prognostic information remains for the time being illusive.

PMID- 15943739
TI  - Clinical experience with Crohn's disease.
AB  - AIM: To determine the clinical spectrum of Crohn's disease in a surgical
      practice, and to show the safety and efficacy of the range of procedures
      performed. METHODS: A consecutive series of 92 patients with Crohn's disease who
      presented between January 1988 and August 2001 to a surgical practice were
      studied. RESULTS: Ninety two patients (42 male, 50 female), with a mean age of 43
      years (range 19-91 years) underwent surgery between January 1998 and August 2001.
      The mean length of follow up was 46 months (range 1-166 months). Forty patients
      had disease in more than one site, compared with 52 patients with single site
      disease. In total, 184 procedures were performed. Patients with the combination
      of colonic and anorectal disease required more surgical interventions than
      patients with other disease distributions. At follow up, all patients with
      disease confined to the small intestine or ileocaecal region were free of
      symptoms with the only nine taking medication. No patients presenting with
      colonic disease had symptomatic disease or were taking any anti-inflammatory
      medication at time of follow up. However, in the group of patients with anorectal
      or the combination of colonic and anorectal disease, 42% had ongoing symptoms
      (predominantly anorectal). Fifteen patients had a stoma at some point during
      their surgical course. CONCLUSION: In a tertiary referral setting, surgical
      treatment of Crohn's disease can carry a low morbidity with good relief and
      control of symptoms when used for specific indications. Those with small bowel or
      colonic disease have better outcomes following surgery compared to those with
      anorectal disease.

PMID- 15943741
TI  - Phrenology and the neurosciences: contributions of F. J. Gall and J. G.
      Spurzheim.
AB  - The pseudoscience of phrenology arose from the observations and intuitions of
      Franz Joseph Gall (1758-1828) and his disciple Johann Gaspar Spurzheim (1776
      1832). Gall believed that mental functions are localized in discrete parts of the
      brain, which he called organs. He located the organs subserving intellectual
      functions chiefly in the cerebral cortex. To support this doctrine, Gall and
      Spurzheim carried out extensive neuro-anatomical studies, and made some important
      discoveries. The Gordon Craig Library contains a book by Spurzheim on the anatomy
      of the brain, published in London in 1826, which summarizes these discoveries.
      Gall also believed that the functional strength of the cerebral and cerebellar
      organs was expressed by their bulk: a well-developed organ caused a bulge in the
      overlying cranial bone. Hence, feeling the bumps of the skull was a means of
      assessing the individual's personality. This very fallacious component of Gall's
      doctrine had great influence in the nineteenth century, affecting psychiatry,
      criminology and educational theory. Further research demolished Gall's doctrine,
      and phrenology sank into disrepute. Nevertheless, phrenological thinking played
      an important part in the growth of clinical neurology in the second half of the
      nineteenth century.

PMID- 15943742
TI  - College portraits, surgeons and the Archibald Prize.
AB  - The Royal Australasian College of Surgeons is fortunate to have a wonderful
      collection of portraits, which date from William Cheselden's portrait in the mid
      18th century to the latest of immediate past president, Kingsley Faulkner. Many
      of the portraits are of former College presidents. The presidents have often been
      painted by the leading artist of the day, many of whom won the Archibald Prize.
      There are many connections between surgeons and the Archibald Prize, the most
      prestigious award in Australian art.

PMID- 15943743
TI  - Physick: in the style of John Wesley.

PMID- 15943744
TI  - Chemistry of Antoine Baume (1774).

PMID- 15943745
TI  - Delayed thoracic oesophageal perforation by duck bone.

PMID- 15943746
TI  - Cauda equina syndrome secondary to constipation: an uncommon occurrence.
AB  - Suspected spinal cord or cauda equina pathology is an emergency that must be
      dealt with swiftly, with appropriate referral and investigations. Constipation is
      a clinical diagnosis of exclusion, but should not be forgotten as a cause of
      major morbidity when severe in nature. It can mimic an acute abdomen, sepsis and
      even spinal cord pathology. We describe a case of cauda equina syndrome in a
      young man. The pathology responsible was found to be constipation with faecal
      impaction, once nerve and bony pathology were excluded. When treated, there was
      almost immediate resolution of the neurologic signs and urinary retention.

PMID- 15943747
TI  - Mirizzi syndrome.

PMID- 15943749
TI  - Re: Synovial sarcoma- towards a simplified approach to prognosis.

PMID- 15943750
TI  - Major vascular injury following percutaneous nephrolithotomy.

PMID- 15943751
TI  - Rectus sheath haematoma presenting as acute abdomen.

PMID- 15943752
TI  - Trends in clinical toxicology: advances that may change your practice.
AB  - Recent studies have had a significant impact on the practice of Medical
      Toxicology. We review selected articles that have advanced our thinking about
      consequential issues such as gastrointestinal decontamination, paracetamol
      poisoning, ethanol withdrawal, cocaine-associated chest pain, carbon monoxide
      poisoning and over-anticoagulation.

PMID- 15943753
TI  - Tumour necrosis factor receptor 1 and hepatocyte regeneration in acetaminophen
      toxicity: a kinetic study of proliferating cell nuclear antigen and cytokine
      expression.
AB  - To determine the importance of tumour necrosis factor receptor 1 in hepatocyte
      regeneration in acetaminophen toxicity, wild type and tumour necrosis factor
      receptor 1 knock-out mice were dosed with acetaminophen (300 mg/kg
      intraperitoneally) and sacrificed at 4, 24, 48, 72, and 96 hr. Biochemical
      parameters (alanine aminotransferase, ALT) and histologic evidence of
      hepatocellular injury were comparable in the two groups of mice. To examine the
      effects of tumour necrosis factor receptor 1 on hepatocyte regeneration,
      immunohistochemical staining with proliferating cell nuclear antigen was
      performed. Immunohistochemical staining for proliferating cell nuclear antigen
      was significantly reduced at multiple time points in the knock-out mice and did
      not normalize until 96 hr. To evaluate the effect of tumour necrosis factor
      receptor 1 depletion on cytokines known to be involved in regeneration, levels of
      macrophage inhibitory protein 2, interferon-gamma-inducible protein-10 and
      monocyte chemoattractant protein 1 were compared in the two groups of mice.
      Significant elevation of all cytokines was observed in both groups of mice;
      however, higher levels were present in the knock-out mice. Depletion of tumour
      necrosis factor receptor 1 has long-lasting effects on hepatocyte regeneration in
      acetaminophen toxicity but multiple other factors appear to orchestrate eventual
      recovery in these mice.

PMID- 15943754
TI  - Comparative effects of curcumin and an analogue of curcumin in carbon
      tetrachloride-induced hepatotoxicity in rats.
AB  - We have evaluated the comparative effect of curcumin (diferuloyl methane) and its
      analogue [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] (BDMC-A) on carbon
      tetrachloride-induced hepatotoxicity in rats. Administration of carbon
      tetrachloride (3 ml/kg/week) for three months significantly (P<0.05) increased
      the levels of marker enzymes such as aspartate transaminase (AST), alkaline
      phosphatase (ALP) and gamma-glutamyl transferase (GGT). The levels of plasma
      thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides were
      also significantly (P<0.05) increased. We have observed a significant (P<0.05)
      decrease in the levels of plasma reduced glutathione (GSH), vitamin C and vitamin
      E. There was a significant (P<0.05) increase in the levels of TBARS and
      hydroperoxides in liver and kidney and a significant (P<0.05) decrease in the
      activities of enzymic antioxidants- superoxide dismutase (SOD), catalase and GSH
      peroxidase along with GSH in CCl(4)-treated rats. Oral administration of curcumin
      and BDMC-A to CCl(4)-induced rats for a period of three months significantly
      (P<0.05) decreased the levels of marker enzymes, plasma TBARS and hydroperoxides
      and increased the levels of plasma and tissue antioxidants. Histopathological
      studies of liver also showed protective effect of curcumin and BDMC-A. We have
      observed thickening of blood vessels and microvesicular fatty changes around the
      portal triad in CCl(4)-treated rat liver. Treatment with curcumin showed only
      mild sinusoidal dilatation while with BDMC-A there was only mild portal
      inflammation. The effect exerted by BDMC-A was found to be more promising than
      curcumin.

PMID- 15943755
TI  - Long-term parathyroid- and c-cell function after radioiodine for benign thyroid
      diseases.
AB  - The study examined static and dynamic parathyroid hormone and calcitonin
      secretion after radioiodine, and was a retrospective study of patients having
      received radioiodine for benign conditions 8-12 years earlier. In one group of
      patients parathyroid hormone and calcium were measured as single blood tests, in
      a second group of patients parathyroid hormone and calcitonin secretion capacity
      were measured during a hypocalcaemic citrate-clamp and a hypercalcaemic
      stimulation test. Baseline calcium and parathyroid hormone were normal within
      expected ranges 8-12 years after radioiodine. Stimulated parathyroid hormone or
      calcitonin secretion did not differ from an age- and gender-matched control
      group. Radioiodine in doses used for benign thyroid diseases appears safe with
      regard to parathyroid hormone and calcitonin secretion.

PMID- 15943756
TI  - The superoxide dismutase mimetic, tempol, reduces the bioavailability of nitric
      oxide and does not alter L-NAME-induced hypertension in rats.
AB  - L-NAME-induced hypertension is characterized by chronic inhibition of nitric
      oxide synthesis. We have investigated if tempol, an agent mimicking superoxide
      dismutase might reduce hypertension and the increased vascular reactivity to
      pressor agents. Rats were divided into: Control, animals receiving L-NAME 50 mg
      kg(-1)day(-1), tempol 200 mg kg(-1)day(-1) and tempol plus L-NAME. Drugs were
      administrated in the drinking water for seven days. L-NAME increased mean
      arterial blood pressure (Control: 108+/-3 mmHg versus L-NAME 181+/-5 mmHg;
      P<0.05). Tempol did not change arterial pressure and heart rate in L-NAME and
      Control groups. The reactivity to phenylephrine increased in the L-NAME group
      (E(max) Control: 2.00+/-0.15 g versus L-NAME: 2.45+/-0.14 g); tempol+L-NAME
      (E(max): 2.55+/-0.15 g) and in the tempol group (E(max): 2.57+/-0.14 g). Maximal
      relaxation induced by acetylcholine was reduced in L-NAME group (60.9+/-3%) and
      tempol+L-NAME (37.4+/-6%) compared to Control (99.1+/-0.12%) and tempol groups
      (95.6+/-2.12%). All treated groups presented a reduction in the effects of L-NAME
      administration on basal vascular tone. Our results show that tempol, in the dose
      used in this study, did not change the effects of L-NAME on blood pressure which
      suggests that tempol reduces bioavailability of nitric oxide on aortic isolated
      ring.

PMID- 15943757
TI  - Evaluation of a barrier cream against the chemical warfare agent VX using the
      domestic white pig.
AB  - The purpose of this study was to evaluate the efficacy of a novel barrier cream
      formulation at reducing the percutaneous toxicity of a 2xLD(50) liquid challenge
      of nerve agent (VX). The study was conducted in vitro and in vivo using the
      domestic pig. Pretreatment of the (inner ear skin) exposure site with barrier
      cream eliminated mortality, reduced cholinesterase inhibition and prevented any
      physiological or biochemical signs of intoxication. In contrast, untreated
      animals exposed to VX exhibited severe signs of intoxication, near total AChE
      inhibition and generally died within the (3 hr) exposure period (5/6 animals).
      Application of the barrier cream caused a significant decrease in the area of
      skin contaminated by VX. It was tentatively concluded that spreading was
      predominantly a surface phenomena (possibly mediated by capillary movement of the
      agent through the microrelief or between hair follicles) with little or no
      contribution from lateral diffusion within the stratum corneum. There was a
      disparity between the in vitro and in vivo skin absorption measurements that was
      ascribed to the absence of systemic clearance in vitro. However, both models
      indicated a substantial reservoir of VX within the skin, providing a potential
      strategy for future investigations into "catch-up therapies". In summary, the
      novel barrier cream formulation was effective against a 2xLD(50) (liquid,
      percutaneous) dose of VX applied for 3 hr. Further work should be conducted to
      investigate more pragmatic issues such as optimal reapplication frequency and
      environmental effects such as temperature and humidity.

PMID- 15943758
TI  - A comparison of the antinociceptive and adverse effects of the mu-opioid agonist
      morphine and the delta-opioid agonist SNC80.
AB  - delta-Opioid receptor agonists have been postulated to induce analgesia without
      the adverse effects commonly associated with mu-opioids e.g. morphine. In the
      present study, we evaluated the occurrence of antinociceptive and opioid-like
      side effects in rats (n=5-7) treated with a single dose of subcutaneous morphine
      (0.01 to 40 mg/kg) or SNC80 (0.63 to 80 mg/kg). The antinociceptive effects of
      morphine and SNC80 were compared using a range of nociceptive tests including the
      tail withdrawal test, the acetic acid-induced abdominal constriction (writhing)
      assay, the automated formalin test and a model of inflammation-induced thermal
      hyperalgesia. The adverse effects of both drugs were examined in animal models
      for gastrointestinal (GI) inhibition (charcoal test; ricinus oil test),
      respiratory depression (blood-gas analysis), motor disturbances (automated
      rotarod model) and abuse liability (drug discrimination learning). Morphine
      displayed significant antinociceptive and adverse effects in all the animal
      models employed. SNC80 exhibited a significant effect in the writhing test and
      limited efficacy in a model of inflammation-induced thermal hypersensitivity. A
      delay in the occurrence of diarrhoea and some limited increases in PCO(2) were
      observed with the higher doses of SNC80 (> or =40 mg/kg). In conclusion, the
      delta-opioid agonist SNC80 lacks both the analgesic efficacy and adverse effects
      of mu-opioids. However, the activity of SNC80 in the inflammatory model suggests
      delta-opioid agonists may be useful analgesics in the treatment of some forms of
      inflammatory pain.

PMID- 15943759
TI  - Intramuscular injection of hypertonic saline: in vitro and in vivo muscle tissue
      toxicity and spinal neurone c-fos expression.
AB  - Intramuscular injection of hypertonic saline (4-6% NaCl) is widely used to induce
      muscle pain in volunteers. The quality of the pain is comparable to clinical
      muscle pain with localised and referred pain. The objective was to evaluate the
      muscle toxicity of hypertonic saline by characterisation of 1) cytotoxicity in
      vitro, 2) local muscle toxicity in rabbits and 3) number of spinal dorsal horn
      neurones expressing c-fos after intramuscular injection in pigs as an indicator
      of nociception. Rat myocyte cultures and erythrocyte suspensions were treated
      with hypertonic NaCl solutions. The creatine kinase activity remaining in the
      myocytes and haemolysis were measured. Groups of six rabbits were given an
      intramuscular injection of 0.5 ml of 0.9, 3 or 6% NaCl. Three days later,
      creatine kinase activity was determined in injection site muscle tissue and
      normal contralateral muscle. The amount of injection site muscle tissue totally
      depleted of creatine kinase was calculated. Groups of two pigs were given an
      intramuscular injection of 3.0 ml of 6% NaCl. The spinal cord was sampled 1, 2 or
      3 hr later and processed for stereological quantification of the number of dorsal
      horn neurones expressing c-fos. Saline was not toxic in vitro at 0.9-6%, but
      toxic to erythrocytes at 7% or higher and rat myocytes at 15% or higher. No
      muscle toxicity was seen in rabbits. The number of dorsal horn neurones
      expressing c-fos was not above basal level. In conclusion, 6% saline caused no in
      vitro or in vivo toxicity in sensitive models. Consequently, the pain caused by
      intramuscular injection of hypertonic saline is most likely not related to tissue
      damage. Consistently, intramuscular injection of 6% NaCl did not activate dorsal
      horn neurones in pigs to express c-fos beyond basal level.

PMID- 15943760
TI  - Pyridoxine attenuates chromium-induced oxidative stress in rat kidney.

PMID- 15943761
TI  - Association between sharing of toothbrushes, eating and drinking habits and the
      presence of Actinobacillus actinomycetemcomitans in Moroccan adolescents.
AB  - BACKGROUND/AIMS: Actinobacillus actinomycetemcomitans is frequently detected in
      dental plaque collected from Moroccan adolescents, and has been shown to be
      associated with clinical attachment loss in this population. The aim of this
      study was to assess whether behaviors such as the sharing of toothbrushes, and
      eating and drinking habits were associated with the presence of A.
      actinomycetemcomitans in Moroccan adolescents. MATERIALS AND METHODS: A total of
      121 adolescents were clinically examined. Interviews regarding sharing of
      toothbrushes, eating and drinking habits were performed, and plaque samples were
      collected and analyzed for A. actinomycetemcomitans with different leukotoxin
      promoter types by polymerase chain reaction. Based on eating and drinking habits,
      the study population was divided in a low risk behavior group (LRB) and a high
      risk behavior group (HRB). RESULTS: No association was found between the sharing
      of toothbrushes and the presence of A. actinomycetemcomitans. The odds ratios
      between the HRB and LRB group for being positive for the JP2 type, for non-JP2
      types, and for any type of A. actinomycetemcomitans were 4.74 (95% CI 0.55;
      40.71), 2.49 (95% CI 1.03; 5.97), and 2.97 (95% CI 1.28; 6.91), respectively. The
      difference in the mean number of teeth with a clinical attachment loss of > or =
      3 mm between the HRB and the LRB group was 0.91(95% CI 0.09; 1.72). CONCLUSION:
      Sharing of toothbrushes does not seem to be associated with the presence of A.
      actinomycetemcomitans in young Moroccans. Eating and drinking habits conducive to
      exchange of saliva are positively associated with presence of A.
      actinomycetemcomitans, and with a higher level of clinical attachment loss.

PMID- 15943762
TI  - Oral and vaginal epithelial cell anti-Candida activity is acid labile and does
      not require live epithelial cells.
AB  - BACKGROUND: Candida albicans is the causative agent of oral and vaginal
      candidiasis. Innate host defenses against C. albicans are important against each
      infection. Among these are oral and vaginal epithelial cells that have anti
      Candida activity. The mechanism of action includes a requirement for cell contact
      with no role for soluble factors, and a putative role for carbohydrates based on
      the sensitivity of the activity to periodic acid. METHODS: Periodic acid
      treatment of epithelial cells as well as the property of partial resistance of
      antifungal activity to fixation was used to further dissect the mechanism of
      action. RESULTS: The results herein effectively now challenge a role for
      carbohydrates alone. Firstly, the putative carbohydrate(s) released into
      supernatants of periodic acid-treated epithelial cells could not compete with
      fresh epithelial cells for activity, and equivalent abrogation of activity was
      observed by periodic acid-treated cells irrespective of the amount of
      carbohydrate released. Instead, the similar abrogation of activity following
      treatment with other acids or when cocultured under acidic conditions suggests
      that the activity is acid-labile. Finally, while activity requires intact
      epithelial cells, it does not require live cells; activity was minimally affected
      by fixing epithelial cells prior to coculture where the majority of cells
      remained impermeable to Trypan blue but were defined as non-viable by positive
      nuclear staining with propidium iodide. CONCLUSION: These results suggest that
      antifungal activity is dependent on contact by intact, but not necessarily live,
      epithelial cells through an acid-labile mechanism.

PMID- 15943763
TI  - Microbicidal efficacy of ozonated water against Candida albicans adhering to
      acrylic denture plates.
AB  - BACKGROUND/AIMS: Ozone is known to act as a strong antimicrobial agent against
      bacteria, fungi, and viruses. We examined the effect of ozonated water on Candida
      albicans on acrylic denture plate. METHODS: The heat-cured acrylic resins were
      cultured with C. albicans. After treatment of flowing ozonated water, the number
      of attached C. albicans was counted. In some experiments, the test samples were
      treated with ozonated water in combination with ultrasonication. RESULTS: After
      exposure to flowing ozonated water (2 or 4 mg/l) for 1 min, viable C. albicans
      cells were nearly nonexistent. The combination of ozonated water and
      ultrasonication had a strong effect on the viability of C. albicans adhering to
      the acrylic resin plates. There were no significant differences in antimicrobial
      activity against C. albicans between plates immersed in ozonated water with
      ultrasonication and those treated with commercially available denture cleaners.
      In addition, electron microscopic analysis revealed that small amounts of C.
      albicans remained on the plate after exposure to flowing ozonated water or
      immersion in ozonated water with ultrasonication. CONCLUSION: Our results suggest
      that application of ozonated water may be useful in reducing the number of C.
      albicans on denture plates.

PMID- 15943764
TI  - Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia and
      Prevotella nigrescens in endodontic lesions detected by culture and by PCR.
AB  - he aim of this study was to investigate the presence of four black-pigmented
      bacteria, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella
      intermedia and Prevotella nigrescens, in endodontic infections by culture and
      polymerase chain reaction (PCR) analyses. Microbial samples were obtained from 50
      teeth with untreated necrotic pulps (primary infection) and from 50 teeth with
      failing endodontic treatment (secondary infection). Microbiological strict
      anaerobic techniques were used for serial dilution, plating, incubation, and
      identification. For PCR detection, the samples were analyzed using species
      specific primers of 16S rDNA and the downstream intergenic spacer region. Culture
      and PCR detected the test species in 13/100 and 50/100 of the study teeth,
      respectively. The organisms were cultured from 11/50 (22%) of primarily infected
      root canal samples and from 2/50 (4%) of secondary root canal samples. PCR
      detection identified the target species in 32/50 (64%) and 18/50 (36%) of primary
      and secondary infections, respectively. P. gingivalis was rarely isolated by
      culture methods (1%), but was the most frequently identified test species by PCR
      (38%). Similarly, P. endodontalis was not recovered by culture from any tooth
      studied, but was detected by PCR in 25% of the sampled teeth. PCR-based
      identification also showed higher detection rates of P. intermedia (33%) and P.
      nigrescens (22%) than culture (13%). In conclusion, P. gingivalis, P.
      endodontalis, P. intermedia, and P. nigrescens were identified more frequently in
      teeth with necrotic pulp than in teeth with failing endodontic treatment. Also, a
      higher frequency of black-pigmented species was detected by PCR than by culture.

PMID- 15943765
TI  - Detection of periodontopathic bacteria and an oxidative stress marker in saliva
      from periodontitis patients.
AB  - We assessed the salivary levels of periodontopathic bacteria and 8
      hydroxydeoxyguanosine (8-OHdG) in patients with periodontitis. The salivary
      levels of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and
      Tannerella forsythia (formerly Bacteroides forsythus) were assessed using real
      time polymerase chain reaction. The 8-OHdG levels were determined using an enzyme
      linked immunosorbent assay. The salivary levels of 8-OHdG, P. gingivalis, and T.
      forsythia in the periodontitis patients were significantly higher than those in
      healthy subjects. By contrast, the A. actinomycetemcomitans level in healthy
      subjects was higher than that in periodontitis patients. 8-OHdG was significantly
      correlated with P. gingivalis. Statistically significant decreases in the levels
      of P. gingivalis, probing depth, bleeding on probing, and 8-OHdG were observed
      after initial periodontal treatment. These results suggest that the 8-OHdG levels
      in saliva reflect the load of periodontal pathogens. 8-OHdG could be a useful
      biomarker for assessing periodontal status accurately, and for evaluating the
      efficacy of periodontal treatment.

PMID- 15943766
TI  - Antimicrobial effects of essential oils in combination with chlorhexidine
      digluconate.
AB  - The aim of the present study was to compare antimicrobial effects of essential
      oils alone and in combination with chlorhexidine digluconate against planktonic
      and biofilm cultures of Streptococcus mutans and Lactobacillus plantarum. The
      essential oils included cinnamon, tea-tree (Melaleuca alternifola), manuka
      (Leptospermum scoparium), Leptospermum morrisonii, arnica, eucalyptus,
      grapefruit, the essential oil mouthrinse Cool Mint Listerine and two of its
      components, menthol and thymol. Cinnamon exhibited the greatest antimicrobial
      potency (1.25-2.5 mg/ml). Manuka, L. morrisonii, tea-tree oils, and thymol also
      showed antimicrobial potency but to a lesser extent. The combination effect of
      the essential oil-chlorhexidine was greater against biofilm cultures of both S.
      mutans and L. plantarum than against planktonic cultures. The amount of
      chlorhexidine required to achieve an equivalent growth inhibition against the
      biofilm cultures was reduced 4-10-fold in combination with cinnamon, manuka, L.
      morrisonii, thymol, and Listerine. We conclude that there may be a role for
      essential oils in the development of novel anticaries treatments.

PMID- 15943767
TI  - In vitro activity of a monoclonal killer anti-idiotypic antibody and a synthetic
      killer peptide against oral isolates of Candida spp. differently susceptible to
      conventional antifungals.
AB  - BACKGROUND/AIMS: A monoclonal killer anti-idiotypic antibody (mAbK10) and a
      synthetic killer peptide, acting as internal images of a microbicidal, wide
      spectrum yeast killer toxin (KT) have been recently shown to express candidacidal
      in vitro and an in vivo therapeutic activity against experimental mucosal and
      systemic candidosis models caused by a reference strain of Candida albicans
      (10S). MATERIAL AND METHODS: The in vitro candidacidal activity of mAbK10 and
      synthetic killer peptide was compared using a colony forming unit assay against a
      large number of isolates of different Candida spp., obtained from oral saliva of
      adult diabetic (type 1 and 2) and nondiabetic subjects from Parma (Italy) and
      London (UK). RESULTS: Both the KT-mimics exerted a strong dose-dependent
      candidacidal activity, probably mediated by the interaction with beta-glucan KT
      receptors on target yeast cells, against all the tested strains, regardless of
      their species and pattern of resistance to conventional antifungal agents.
      CONCLUSIONS: These observations open new perspectives in the design and
      production of candidacidal compounds whose mechanism reflects that exerted in
      nature by killer yeasts.

PMID- 15943768
TI  - Differential display analysis of Porphyromonas gingivalis gene activation
      response to heat and oxidative stress.
AB  - BACKGROUND/AIMS: The etiologic relationship between periodontitis and
      Porphyromonas gingivalis is attributed to the ability of the organism to express
      a variety of virulence factors, many of which are cell surface components
      including lipopolysaccharide and arginine-specific cysteine proteases (Arg
      gingipains, RgpA, and RgpB). P. gingivalis responds to the stress of rapid
      elevation in temperature by activating a set of genes to produce heat shock
      proteins that mediate the effects of sudden changes in environmental temperatures
      by repairing or eliminating cellular proteins denatured by that stress. METHODS:
      We used restriction fragment differential display (RFDD) to identify and measure
      the genes expressed by surrogates of environmental stresses, heat and oxidative
      stress. The results were then confirmed using quantitative reverse-transcription
      polymerase chain reaction. RESULTS: We selected 16 genes differentially induced
      from over 800 total expression fragments on the RFDD gels for further
      characterization. With primers designed from those fragments we found that a + 5
      degrees C heat shock caused a statistically significant increase in expression
      compared 12 of 18 untreated genes tested. The exposure of P. gingivalis to
      atmospheric oxygen resulted in statistically significant increases in five of the
      target genes. These genes are likely involved in transport and synthesis of
      components of the lipopolysaccharide biosynthetic pathway important in anchoring
      the Arg-gingipains required for virulence-related activities. CONCLUSION: These
      results emphasize the need for studies to measure the coordinated responses of
      bacteria like P. gingivalis which use a multitude of interrelated metabolic
      activities to survive the environmental hazards of the infection process.

PMID- 15943770
TI  - Antimicrobial susceptibility variation of 50 anaerobic periopathogens in
      aggressive periodontitis: an interindividual variability study.
AB  - BACKGROUND/AIMS: The frequent use of antibiotics in developed countries has led
      to the emergence of widespread bacterial resistance. In this study, the
      interindividual variability of the antibiotic susceptibility of 50 putative
      microorganisms in aggressive periodontitis patients has been evaluated by means
      of VC (variation coefficient). MATERIAL AND METHODS: A total of 60 microbial
      samples were collected from 20 adult patients diagnosed with aggressive
      periodontitis (2-4 samples by patient). Bacterial strains of Porphyromonas
      gingivalis, Prevotella intermedia, Tannerella forsythia, Fusobacterium nucleatum,
      and Peptostreptococcus micros were isolated according to Slots' rapid
      identification method. The susceptibilities to 10 antibiotics were studied:
      penicillin G (PEN), ampicillin (AMP), amoxicillin (AMX), amoxicillin/clavulanate
      (AMC), tetracycline (TET), doxycycline (DOX), ciprofloxacin (CIP), erythromycin
      (ERY), spiramycin (SPI) and clindamycin (CLIN), using the Disk Diffusion
      Susceptibility test (DDS test: Kirby-Bauer's modified method for anaerobic
      bacteria). The broth microdilution Minimum Inhibitory Concentration test was
      carried out as a control test. RESULTS: Among the 50 identified bacteria, 15 were
      P. gingivalis, 12 P. intermedia, 8 T. forsythia, 9 F. nucleatum, and 6 P. micros.
      The results of the DDS test show that penicillins (especially AMC, AMP, and AMX),
      cyclines (especially DOX) and CLIN are highly effective against the 50 anaerobic
      studied bacteria. CIP and ERY have the lowest efficacy against those bacteria.
      CIP shows a very variable activity according to anaerobic bacteria species, being
      particularly inactive against P. gingivalis and very efficient against T.
      forsythia and P. micros. SPI is also highly efficient but not against P. micros.
      CONCLUSIONS: The interindividual susceptibility of principal periodontal
      pathogens to antibiotics is not homogeneous and seems to vary according to
      bacterial species and antimicrobial molecules. This variability seems to be
      greater with older molecules (PEN, TET, ERY) than with more recent ones, which
      indicates more stable results (AMC, AMX, AMP, and DOX). P. intermedia appeared to
      be the bacteria most resistant to penicillins and showed the highest coefficient
      variation. Together with scaling and root planing, the combination of two
      antibiotics would therefore seem to be recommended in the treatment of aggressive
      periodontitis, particularly in the presence of P. intermedia.

PMID- 15943769
TI  - Effect of female sex hormones on Campylobacter rectus and human gingival
      fibroblasts.
AB  - Recent studies have suggested a relationship between maternal Campylobacter
      rectus infections and preterm low birth weight. The purpose of this study was to
      investigate the effect of female sex hormones, estradiol and progesterone, on C.
      rectus and human gingival fibroblasts (HGF). The growth of C. rectus was
      significantly enhanced by incorporating either estradiol or progesterone in the
      culture medium. The production of vascular endothelial growth factor (VEGF),
      interleukin (IL)-6 and IL-8 by HGF increased following stimulation with estradiol
      or progesterone, at concentrations comparable to those present in the plasma of
      pregnant women. In addition, a significantly higher secretion of VEGF by HGF
      treated with the combination of C. rectus and estradiol was observed in
      comparison with a treatment with C. rectus alone. Stimulation of HGF with VEGF
      resulted in production of IL-6 and IL-8 in a dose-dependent manner. The capacity
      of female sex hormones to enhance both C. rectus growth and VEGF, IL-6, and IL-8
      production by HGF has the potential to contribute to periodontal disease
      progression during pregnancy.

PMID- 15943771
TI  - Microarrays complement culture methods for identification of bacteria in
      endodontic infections.
AB  - The aim of this study was to investigate the microbial composition of necrotic
      root canals using culture methods and microarray technology. Twenty uniradicular
      teeth with radiographic evidence of periapical bone loss and with no previous
      endodontic treatment were selected for this study. For molecular diagnosis a DNA
      chip with 20 different species-specific, 16S-rDNA-directed catcher probes was
      used. The microorganisms most frequently detected by the DNA chip were:
      Micromonas micros, Fusobacterium nucleatum ssp., Tannerella forsythia, Treponema
      denticola, Veillonella parvula, Eubacterium nodatum, Porphyromonas gingivalis,
      Actinomyces odontolyticus, and Streptococcus constellatus. As expected,
      additional important bacterial taxa were found by culture analysis, but
      microorganisms such as T. forsythia and T. denticola could not be identified. In
      conclusion, microarrays may provide significant additional information regarding
      the endodontic microbiota by detecting bacterial species that are otherwise
      difficult or impossible to culture.

PMID- 15943773
TI  - Draft reports for public comment from the US Secretary's Advisory Committee on
      Xenotransplantation.

PMID- 15943774
TI  - ''Homologous restriction'' in complement lysis: roles of membrane complement
      regulators.
AB  - The complement system is a powerful bactericidal immune defence with the
      potential to damage self cells. Protection of self is provided by expression on
      cells of a battery of membrane regulators that inhibit activation of complement.
      Roles of complement in the rejection of transplanted organs have long been
      recognized, and are particularly relevant in xenotransplantation, where
      hyperacute rejection is complement-driven. Inhibiting complement was therefore
      considered early in the history of xenografting, and the use of membrane
      complement regulators to this end was proposed more than two decades ago. For
      each of the membrane regulators in humans, early studies implied a species
      specificity of action, inhibiting human complement but not that from other
      species. The dogma of species-specificity dictated strategies for inhibiting
      complement in xenografts and drove the creation of donor transgenic pigs
      expressing human regulators. Here we critically evaluate the evidence for species
      specificity in membrane complement regulators from humans and other animals. We
      challenge the dogma and show that there is considerable cross-species activity
      for each of the membrane regulators of complement. Acceptance of the fact that
      species selectivity is not a limitation will open new avenues for protection of
      the xenograft from complement damage.

PMID- 15943775
TI  - Comparison of select innate immune mechanisms of fish and mammals.
AB  - The study of innate immunity has become increasingly popular since the discovery
      of homologs of many of the innate immune system components and pathways in lower
      organisms including invertebrates. As fish occupy a key position in the evolution
      of the innate and adaptive immune responses, there has been a great deal of
      interest regarding similarities and differences between their defense mechanisms
      and those of higher vertebrates. This review focuses on describing select
      mechanisms of the innate immune responses of fish and the implications for
      evolution of immunity in higher vertebrates.

PMID- 15943776
TI  - Reducing Gal expression on the pig organ - a retrospective review.
AB  - The rejection caused by the presence of Galalpha1,3Gal (Gal) on the pig vascular
      endothelium and of natural anti-Gal antibodies in human blood has recently been
      prevented by the breeding of pigs that do not express Gal, achieved by knocking
      out the gene for the enzyme, alpha1,3-galactosyltransferase. However, prior to
      the introduction of nuclear transfer/embryo transfer techniques, a major effort
      was directed towards reducing Gal expression on pig cells by other methods, such
      as by cleaving Gal from the underlying substrate, or replacing Gal with an
      alternative, innocuous oligosaccharide by a process that has been termed
      'competitive glycosylation'. Gal has been cleaved by alpha-galactosidase or endo
      beta-galactosidase C. Competitive glycosylation has largely targeted replacement
      of Gal by insertion of a gene for a fucosyltransferase or a sialyltransferase, or
      by insertions of the gene for N-acetylglucosaminyltransferase III to reduce cell
      surface expression of several oligosaccharides. The results of these approaches
      to render the pig cells less immunogenic to the human immune system are
      summarized. With regard to the problem provided by Gal expression, the above
      approaches may be considered by some to be largely obsolete, but the principles
      underlying them may prove valuable when other antigen targets for human
      antibodies are definitively identified, if these prove to be carbohydrates.

PMID- 15943777
TI  - No evidence of in vitro and in vivo porcine endogenous retrovirus infection after
      plasmapheresis through the AMC-bioartificial liver.
AB  - BACKGROUND: Currently a number of bioartificial livers (BAL) based on porcine
      liver cells have been developed as a treatment to bridge acute liver failure
      patients to orthotopic liver transplantation or liver regeneration. These
      xenotransplantation related treatments hold the risk of infection of treated
      patients by porcine endogenous retrovirus (PERV) released from the porcine cells,
      as in vitro infection experiments and transplantations in immunocompromised mice
      have shown that PERV is able to infect human cells. The Academic Medical Center
      (AMC)-BAL, unlike other BALs, is characterized by direct contact between porcine
      liver cells and human plasma, and might therefore be permissive for PERV
      transfer. METHODS: Prior to a clinical phase I trial, human plasma perfused
      through the AMC-BAL was investigated for PERV DNA and RNA. Moreover productive
      infectivity was analyzed by exposing the plasma to HEK-293 cells that were
      subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity.
      RESULTS: Although PERV DNA was detected in the perfused plasma, no productive
      infectivity was detected. Consequently fourteen patients were treated with the
      AMC-BAL and monitored for PERV transmission. Immediately after treatment the
      plasma of the patients was positive for PERV DNA, most probably due to porcine
      liver cell lysis. The PERV DNA was cleared within 2 weeks post-treatment and no
      PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)
      293 cells exposed to plasma of treated patients was detectable. CONCLUSION: To
      conclude, no release of infective PERV particles from the AMC-BAL was observed.
      Therefore we consider the AMC-BAL as safe, however careful surveillance of
      patients will be continued.

PMID- 15943778
TI  - Post-transplant upregulation of chemokine messenger RNA in non-human primate
      recipients of intraportal pig islet xenografts.
AB  - BACKGROUND: We have previously shown that pig-to-primate intraportal islet
      xenografts reverse diabetes, escape hyperacute rejection, and undergo acute
      cellular rejection in non-immunosuppressed recipients. To gain a better
      understanding of mechanisms contributing to xenoislet rejection in non-human
      primates we examined gene expression in livers bearing islet xenografts in the
      first 72 h after transplantation. METHODS: Liver specimens were collected at
      sacrifice from seven non-immunosuppressed rhesus macaques at 12, 24, 48 and 72 h
      after intraportal porcine islet transplantation. Following total RNA extraction,
      mRNA was quantified using SYBR green real-time reverse transcription polymerase
      chain reaction (RT-PCR) for species-specific immune response genes. Data were
      analyzed using comparative cycle threshold (Ct) analysis, adjusted for specific
      primer-efficiencies and normalized to cyclophilin expression. RESULTS: Porcine
      insulin mRNA was detected in all liver samples. Cluster analysis revealed
      differential gene expression patterns at 12 and 24 h (early) compared with at 48
      and 72 h (late) post-transplant. Gene expression patterns were associated with
      histological findings of predominantly neutrophils and only a few lymphocytes at
      12 and 24 h and an increasing number of lymphocytes and macrophages at 48 and 72
      h. Transcript levels of CXCR3 and its ligands, interferon-inducible protein 10
      (IP-10) and monokine induced by IFN-gamma (Mig), significantly increased between
      early and late time points together with expression of MIP-1alpha, regulated on
      activation normal T expressed and secreted protein (RANTES) and MCP-1. CCR5
      showed only a marginal, non-significant increase. Fas ligand, perforin and
      granzyme B transcripts were all elevated at 48 and 72 h post-transplant.
      CONCLUSIONS: Our data suggest that CXCR3, with ligands IP-10 and Mig, is involved
      in T cell recruitment in acute islet xenograft rejection in non-human primates.
      Upregulation of RANTES and MIP-1alpha transcripts in the absence of a significant
      CCR5 increase suggests a possible involvement of other chemokine receptors. MCP-1
      expression is associated with T cell and macrophage infiltration. Elevated
      cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B)
      indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms
      within 48 to 72 h after transplantation. These results identify the CXCR3
      mediated chemoattractant pathway as an immunosuppressive target in pig-to-primate
      islet xenotransplantation.

PMID- 15943779
TI  - Characterization of the swine major histocompatibility complex alleles at eight
      loci in Westran pigs.
AB  - BACKGROUND: Pigs are an important large animal model for transplantation and a
      potential source of xenografts. Swine leukocyte antigen (SLA) molecules are
      strong mediators of alloreactive and xenoreactive immune responses. We have
      characterized the SLA alleles of a new pig line bred for transplantation
      research, the Westran (Westmead Hospital transplantation) pig, described in a
      companion paper. METHODS: Three sixth generation inbred Westran pigs and a Large
      White pig control were used to assess SLA alleles. We examined the SLA-1, SLA-3,
      SLA-6, SLA-2, DQA1, DQB1, DRA1 and DRB1 loci using reverse transcription
      polymerase chain reaction and sequencing-based method. RESULTS: All of the
      Westran pigs had a single allele at each locus, except for the SLA-1 locus.
      Typing of the SLA-1 locus in additional animals indicated that this is most
      likely the result of a duplication of the SLA-1 locus rather than heterozygosity.
      The lack of SLA heterozygosity is consistent with the previous finding of low
      microsatellite marker heterozygosity and is the result of both the recent
      deliberate inbreeding of these pigs and their derivation from a feral stock from
      Kangaroo Island, South Australia, established by the release of a single pair in
      1803. CONCLUSIONS: After comparing DNA and protein sequences of the Westran SLA
      alleles with published GenBank SLA sequences, the SLA class I alleles found in
      the Westran pigs were all novel, while the SLA-DR and DQB1 alleles have been
      previously described in other pig breeds. Characterization of the SLA alleles in
      the Westran pigs has identified novel alleles and will be useful for designing
      protocols for modulation of immune responses to allografts and xenografts.

PMID- 15943780
TI  - Genetic and functional evaluation of the level of inbreeding of the Westran pig:
      a herd with potential for use in xenotransplantation.
AB  - BACKGROUND: The Westran pig has been purposely inbred for use in
      xenotransplantation. The herd originated in the wild from a limited gene pool and
      has been inbred by repeated full-sib matings for nine generations. METHODS: The
      aim of this study was to evaluate the level of inbreeding by functional assays,
      such as bi-directional MLR and reciprocal skin grafts between herd members, and
      by genetic analysis using highly polymorphic genetic markers to calculate the
      level of inbreeding. RESULTS: The MLR between herd members were non-reactive
      whereas there was a prompt response to third party pig lymphocytes, indicative of
      a normal immune responsiveness in Westran pigs but isogenicity of the major
      histocompatibility complex. Skin grafts between male siblings or female sibling
      skin grafts on male recipients showed prolonged survival but with few exceptions
      did not survive beyond 100 days suggesting that by the fifth generation the
      Westran herd was still mismatched at minor histocompatibility antigens. This
      level of functional inbreeding was confirmed by microsatellite analysis of highly
      polymorphic markers, which showed that 52 of 53 chromosomally dispersed markers
      were fixed by the ninth generation. This level of fixation was consistent with 19
      to 20 generations of full-sibling inbreeding. The calculated inbreeding
      coefficient at generation 10 was 0.98159. CONCLUSIONS: This analysis confirms
      that the Westran pig is highly inbred and we propose that analysis of
      chromosomally dispersed highly polymorphic markers is an accurate and
      reproducible method for assessing the level of inbreeding of a pig herd.

PMID- 15943781
TI  - Method for evaluating quality of cultured neonatal pig Sertoli cells.
AB  - BACKGROUND: Sertoli cells (SC) in the testis secrete factors that nourish and
      immunoprotect developing spermatozoa, which have made them the focus of studies
      that aim to generate localized tolerance, particularly for transplantation and
      perhaps autoimmunity. Several methods have been described to isolate these cells,
      which include a two-step enzymatic digestion with limited assessment of the
      culture. Here we describe a one-step method, and a series of tests for
      determining purity, viability, and function of the cultured cells. METHODS: We
      isolated SC from neonatal pigs using Liberase HI digestion. Viability and
      apoptosis of cultured cells were measured by flow cytometry with propidium iodide
      and annexin, respectively. Specific identification of the Sertoli type was made
      by immunodetection of Sox9, vimentin, and Mullerian inhibiting substance.
      Moreover, for functionality we were able to detect clusterin in the cultured
      cells by Western blot. RESULTS: Our isolation method had a yield and purity
      similar to previous reports measured with two-step methods. Viability was 95.22
      +/- 0.57% and apoptotic cells were 10.5 +/- 0.32% after 48 h in culture. At 7
      days, practically all cells expressed Sox9, Mullerian inhibiting substance,
      clusterin, and vimentin. CONCLUSIONS: We describe an alternative strategy for
      preparing and identifying cultured SC for further assays of metabolic activity or
      in transplantation models. Establishing a one-step Liberase-digestion method for
      isolation, evaluating viability and apoptosis by more sensitive methods, and
      detecting specific markers in culture can help to evaluate the quality of
      cultured cells. Specific cell markers for identifying SC may be critical when
      identifying SC outside the testis, in contrast with vimentin which is useful only
      for in situ cells.

PMID- 15943782
TI  - Single nucleotide polymorphisms of the prion protein gene (PRNP) in Chinese pig
      breeds.
AB  - Prion diseases (transmissible spongiform encephalopathies, TSE), as a group of
      fatal neurodegenerative diseases, have affected humans and a variety of other
      mammals. Although no natural TSE have been documented in pigs, appropriate
      precautions need to be taken to prevent the iatrogenic spread of prion disease
      through pig-to-human xenotransplantation. Polymorphisms within the open reading
      frame (ORF) of the single-copy gene of prion protein (PRNP) are associated with
      susceptibility to scrapie in sheep and variant Creutzfeldt-Jacob disease in
      humans. We screened polymorphisms in the PRNP gene of 64 China Experimental
      Minipigs and Beijing Large White pigs. Our findings suggest that the porcine PRNP
      gene is highly homogenous. The amino acid sequences of the mature prion protein
      of all samples tested were identical. Four single nucleotide polymorphisms (G11A,
      G615C, G684A, T726G) in the ORF of the porcine PRNP gene were found, and the G-
      >C nucleotide substitution resulted in a serine to asparaginate amino acid
      substitution at codon 4. We conclude that pigs raised under specific pathogen
      free conditions, with the exclusion of rendered mammalian material for at least
      two generations, will have little risk of being infected with a TSE, and even
      less possibility of transmitting prion disease to humans through
      xenotransplantation.

PMID- 15943784
TI  - Xenotransplantation literature update March-April, 2005.

PMID- 15943783
TI  - Effect of long-term culture on the expression of antigens and adhesion molecule
      in single porcine pancreatic endocrine cells.
AB  - BACKGROUND: Changes in the expression of galactose (Gal) alpha1-3Gal, swine
      lymphocyte antigen (SLA) class II and intracellular adhesion molecule (ICAM)-1 of
      single porcine pancreatic endocrine (PE) cells during the culture period were
      investigated. METHODS: Cultured porcine PE-cells were fixed in 10% buffered
      formalin for histological evaluation. At 1, 3, 6, 9 and 12 weeks of culture, mRNA
      was obtained from porcine PE-cells so that the expression of SLA class II and
      ICAM-1 genes could be examined by reverse transcriptase-polymerase chain
      reaction. RESULTS: The rates of Galalpha1-3Gal and SLA class II-positive cells
      did not decrease during the culture period, but the rates of Galalpha1-3Gal and
      SLA class II strongly positive cells significantly decreased. ICAM-1-positive
      cells were scarcely observed during the culture period. SLA class II and ICAM-1
      mRNAs were detected at 1 and 3 weeks of culture, but were not detected after 6
      weeks of culture. CONCLUSIONS: These results suggest that partial reduction in
      the expression of these antigens could be obtained by a long-term culture.

PMID- 15943785
TI  - Expression pattern of keratin subclasses in pancreatoblastoma with special
      emphasis on squamoid corpuscles.
AB  - Expression patterns of keratins (K), both simple epithelia-type (K7, K8, K18,
      K19) and complex/stratified epithelia-type (K1, K4, K5/6, K10, K13, K14, K15,
      K16, K17), and epithelial membrane antigen (EMA) were immunohistochemically
      studied in six pancreatoblastomas (PBL). In all six tumors, areas with overt
      acinar differentiation (AA), solid areas without any specific differentiation
      (SO), and squamoid corpuscles (SC) were diffusely positive for K8, K18, and K19.
      The AA and SO in all the tumors were diffusely positive for K7, but the SC were
      negative or displayed only scattered reactivity for K7. In three tumors, the AA
      and the SC showed scattered reactivity for K5/6. No reactivity for other
      complex/stratified epithelia-type K was found in any of the examined tumor. All
      tumors were reactive for EMA with consistent predominancy in the SC.
      Ultrastructurally, well-developed desmosome-tonofilament complexes were only
      partially observed in tumor cells comprising the SC. These results implied that
      (i) the SC usually lack a character of complete squamous metaplasia; and (ii) the
      SC have a characteristic phenotype (K8/K18/K19/EMA-positive, K7-negative or
      scatteredly positive) that can potentially be useful to delineate the SC in PBL.

PMID- 15943786
TI  - Aberrant methylation and loss of expression of O-methylguanine-DNA
      methyltransferase in pulmonary squamous cell carcinoma and adenocarcinoma.
AB  - O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that
      protects cells against the carcinogenic effects of alkylating agents. The
      methylation status of the MGMT gene was investigated by methylation-specific
      polymerase chain reaction (PCR) and expression status was investigated by
      immunohistochemistry in 70 cases of pulmonary squamous cell carcinoma (pulmonary
      SqCC), including 23 cases of the central type and 47 cases of the peripheral
      type, and in 53 cases of the peripheral type of pulmonary adenocarcinoma (AC).
      The frequency of MGMT methylation was 36% in SqCC and 42% in AC. Cases with MGMT
      methylation correlated significantly with T factor in SqCC (P = 0.047) and AC (P
      = 0.03). In SqCC, the frequency of MGMT methylation was 26% in the central type
      and 40% in the peripheral type; a significant correlation was not found (P =
      0.29). In AC with mixed subtypes showing MGMT methylation, the level of MGMT
      expression in the bronchioloalveolar carcinoma (BAC) area (non-invasive status)
      was significantly higher than that in the papillary or acinar AC area (invasive
      status; P = 0.0002). This trend was not found in AC with mixed subtypes showing
      no MGMT methylation (P = 0.10). These findings suggest that MGMT inactivation is
      an event that occurs in the late carcinogenic process in SqCC and AC, and that AC
      progress from non-invasive status to invasive status with MGMT inactivation
      induced by the promoter DNA methylation.

PMID- 15943787
TI  - Accumulation of cytoplasmic beta-catenin correlates with reduced expression of E
      cadherin, but not with phosphorylated Akt in esophageal squamous cell carcinoma:
      immunohistochemical study.
AB  - Accumulation of beta-catenin in cytoplasm occurs frequently during the
      pathogenesis of esophageal squamous cell carcinoma (ESCC). The mechanism leading
      to this alteration, however, is largely unknown. In the present study,
      immunohistochemistry was performed for beta-catenin, E-cadherin and Ser473
      phosphorylated Akt (P-Akt) in 44 tissue samples of ESCC and corresponding normal
      esophageal epithelium. Exon 3 of the beta-catenin gene was analyzed by using
      single-strand conformation polymorphism and direct sequencing. In addition to the
      reduced expression of E-cadherin and membranous beta-catenin observed in 65.9%
      and 68% of ESCC tested, respectively, cytoplasmic accumulation of beta-catenin
      was also detected in 68% (30/44) cases. However, only two cases were found to
      have the same beta-catenin gene mutation. The data showed that cytoplasmic
      accumulation of beta-catenin was significantly associated with reduced expression
      of E-cadherin (P < 0.05) and that of membranous beta-catenin (P < 0.05).
      Furthermore, cytoplasmic beta-catenin was correlated significantly with lymph
      node metastasis (P < 0.05). In contrast, although strong staining of P-Akt
      occurred in 14 of 44 cases (32%), there was no significant correlation between
      the positive staining of P-Akt and cytoplasmic beta-catenin. Taken together these
      results suggest that the lost membranous beta-catenin might translocate to
      cytoplasm depending on reduced expression of E-cadherin, while Akt seems unlikely
      to play a role in this process.

PMID- 15943788
TI  - Comparison between immunohistochemistry and chromogenic in situ hybridization in
      assessing HER-2 status in breast cancer.
AB  - Human epidermal growth factor receptor-2 (HER-2) is usually determined as a
      potential target for breast cancer therapy. The purpose of the present study was
      to compare chromogenic in situ hybridization (CISH) with immunohistochemistry
      (IHC) in determination of HER-2 status, in metastatic breast cancer patients
      screened for the clinical study of chemotherapy +/- herceptin. It was possible to
      assess both CISH and IHC in 56 cases, using CISH Detection Kit (Zymed) and
      HercepTest (DakoCytomation), respectively. HER-2 was amplified by CISH in 32
      cases (57%) while 33 (59%) were HER-2-positive by IHC. A concordance between HER
      2 status determined by CISH and IHC was noted in 43 of 56 cases (77%; P =
      0.00008). Gene amplification was observed in 6/16 cases (37.5%) in IHC-negative
      subgroup (1+), while no amplification was observed in 5/10 cases (50%) in the IHC
      positive subgroup (2+). These results suggest that there was a greater
      heterogeneity on the genetic level and that simple IHC classification was not
      sufficient. It is suggested that CISH could be considered as a useful additional
      method to IHC in determining HER-2 status in breast cancer patients, with a
      recommendation for testing not only the 2+ but also the 1+ subgroup of patients.

PMID- 15943789
TI  - Expression of survivin and of antigen detected by a novel monoclonal antibody,
      T332, is associated with outcome of diffuse large B-cell lymphoma and its
      subtypes.
AB  - Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non
      Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The
      present study investigates the significance of survivin and a novel monoclonal
      antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL
      and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB
      type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of
      60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of
      survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis
      (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or
      NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However,
      T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-)
      cases (P = 0.01 and 0.02, respectively) while there was no significant survival
      difference between the T332(+) and T332(-) groups of GCB (P = 0.11).
      Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly
      worse prognosis (P = 0.009) than the remaining single positive and double
      negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might
      be a good predictor of DLBCL and its subtypes.

PMID- 15943790
TI  - Establishment and characterization of new cell lines derived from melanotic
      neuroectodermal tumor of infancy arising in the mandible.
AB  - Three cell systems (MINT1/2/3) derived from a melanotic neuroectodermal tumor of
      infancy (MNTI) arising in the mandible of a 1-month-old newborn boy have been
      established, and their cytological natures have been characterized. The cells had
      immunopositivities for pan-keratin, vimentin, neuron-specific enolase, S-100
      protein and melanoma-associated antigen (HMB-45). These immunohistochemical
      phenotypes were basically the same as those observed in tissue sections, in
      which, synaptophysin, myelin basic protein, c-myc gene products, carcinoembryonic
      antigen, and epithelial membrane antigen were also immunolocalized in tumor
      cells. Karyotyping analyzes revealed that the chromosome numbers of the three
      cell systems ranged from 60 to 67 with 3n ploidies, and that there were many
      structural aberrations, such as del(11)(q13), del(22)(q13), add(2)(p11),
      add(7)(q22), extra copies for chromosomes 1, 2, 3, 5, 7, 9, 10, 11, 12, 16, 20,
      and 22, der(9)t(9;13)(p13;q12)add(9)(q34), and der(13;21)(q10;q10), which were
      shared by the three cell systems, while der(19)t(11;19)(q13;p13) was found in
      MINT1 and MINT3. When stimulated by endothelin-3 and vitamin D(3), the cells had
      spinous cell shapes with immunopositivities for HMB-45, neurofilament protein and
      glial fibrillary acidic protein, which indicated more neural differentiation. The
      established cell systems will be useful for further investigation on the
      molecular and genetic basis of MNTI to understand its pathogenesis, which is
      largely unknown.

PMID- 15943791
TI  - Individual identification by DNA polymorphism using formalin-fixed placenta with
      whole genome amplification.
AB  - Polymerase chain reaction (PCR) amplification using formalin-fixed material is
      very limited. In the present study the use of 6 week formalin-fixed placenta for
      individual identification was examined based on DNA analyses. The objective of
      the examination was to prove whether the placenta was from a woman who had just
      given birth. DNA extraction was carried out from the maternal blood sample and
      from the formalin-fixed placental samples composed of three parts: maternal side,
      infant side and umbilical cord. One minisatellite (D1S80), 12 short tandem repeat
      (STR) polymorphisms and amelogenin X, Y were investigated. All the polymorphic
      systems were detected in the maternal blood sample. The majority of the DNA
      isolated from the placental tissues had molecular weights of approximately 500
      bp, and only two to four STR loci were amplified using the DNA. In order to
      amplify more DNA polymorphic markers from the formalin-fixed tissues, whole
      genome amplification was performed. After amplification by degenerate
      oligonucleotide-primed PCR (DOP-PCR), the products contained DNA with increased
      molecular weight up to >10 kbp. More DNA loci were typed using the DOP-PCR
      products. Furthermore, large molecular size fragments were purified from the DOP
      PCR products by agarose electrophoresis, and then the D1S80 locus and 12 STR loci
      were successfully amplified using these fragments.

PMID- 15943792
TI  - Adenoid glioblastoma arising in a patient with neurofibromatosis type-1.
AB  - An unusual case of glioblastoma with adenoid structures arising in a 30-year-old
      Japanese woman with neurofibromatosis type-1 (NF1) is reported. The patient was
      admitted to University of Miyazaki Hospital, complaining of headache, nausea and
      vomiting. From the neuroradiological findings the patient was diagnosed as having
      glioblastoma, and the tumor was surgically resected. Histologically, the tumor
      consisted mainly of dark basophilic cells showing prominent tubular or glandular
      structures surrounded by large eosinophilic cells, in addition to the typical
      glioblastoma features in the periphery of the tumor. Both cells showed strong
      stainability with glial fibrillary acidic protein (GFAP) and S-100 protein
      immunohistochemically, so that the tumor was classified as adenoid glioblastoma.
      Several cases of glioblastoma have been reported to reveal the adenoid or
      epithelioid differentiation. The patients with NF1 are prone to develop malignant
      tumors including glioblastoma, but no cases representing adenoid glioblastoma
      associated with NF1 have been reported. This report is considered to be the first
      case of adenoid glioblastoma arising in a patient with NF1. The recognition of
      the existence of epithelial features of glioblastoma would be important in
      differential diagnosis of epithelioid tumors of the brain including metastatic
      carcinomas.

PMID- 15943793
TI  - Histiocytoid breast carcinoma: solid variant of invasive lobular carcinoma with
      decreased expression of both E-cadherin and CD44 epithelial variant.
AB  - Histiocytoid breast carcinoma (HBC) is a rare type of breast carcinoma with
      morphologic characteristics resembling those of histiocytes. Described herein are
      cytological and histological findings in a case of HBC. Fine-needle aspiration
      cytology revealed numerous loosely cohesive tumor cells with abundant foamy to
      granular cytoplasm and bland-appearing nuclei. The resected tumor exhibited a
      solid growth pattern instead of classic invasive lobular patterns observed in
      most reported cases of HBC. However, distinct intracytoplasmic lumina and
      Pagetoid extension to ducts suggested that this tumor was a variant of invasive
      lobular carcinoma. To determine the cause of the loose cellular cohesiveness of
      this HBC, its expression of the epithelium-related cell adhesion molecules E
      cadherin and CD44v8-10 (CD44 epithelial variant) was examined.
      Immunohistochemically, E-cadherin was not detected, similar to most lobular
      carcinomas. Furthermore, competitive reverse transcription-polymerase chain
      reaction (RT-PCR) analyses among alternatively spliced variants of CD44 revealed
      that the ratio of expression of CD44v8-10 to that of CD44v10 (dominant variant in
      leukocytes) was lower than that for the reference breast carcinoma samples. It is
      concluded that the present case of HBC was a solid variant of invasive lobular
      carcinoma exhibiting foamy to granular cytoplasmic change. Decreased expression
      of both E-cadherin and CD44 epithelial variant may be responsible for the loose
      cellular cohesiveness observed in HBC.

PMID- 15943794
TI  - Composite distal nephron-derived renal cell carcinoma with chromophobe and
      collecting duct carcinomatous elements.
AB  - Chromophobe renal cell carcinoma (RCC) and collecting duct carcinoma (CDC) are
      derived from the collecting duct epithelia, although their morphology, molecular
      biologic characteristics and clinical behaviors are quite different. Herein is
      presented a case of RCC possessing the chromophobe RCC and CDC elements occurring
      in a 64 year-old Japanese woman. The patient was referred to Yokohama City
      University Hospital with complaints of persistent back pain and fever. Radiologic
      examinations revealed a left renal tumor, and radical nephrectomy was performed.
      The patient died with multiple metastases, 8 months after the operation. The
      resected tumor showed an invasive growth, and its cut surface was heterogenous
      with hemorrhage and necrosis. Histologically, the tumor was composed of
      chromophobe elements with dedifferentiation, and CDC elements. The chromophobe
      and CDC elements had obvious histological transition. Lectin histochemistry and
      immunohistochemistry confirmed that this tumor was derived from the distal
      nephron. c-KIT, p53 and Ki67 antigen showed differential localization between the
      chromophobe and CDC elements, even in the transitional areas. Along with the
      previous reports, the present case seemed to be composite RCC derived from the
      collecting duct, which might present clues to elucidate carcinogenesis in the
      distal nephron.

PMID- 15943795
TI  - Large cell calcifying Sertoli cell tumor of the testis: comparative
      immunohistochemical study with Leydig cell tumor.
AB  - Large cell calcifying Sertoli cell tumor is a rare type of testicular tumor.
      Reported herein is a Japanese patient with this tumor not associated with
      Carney's complex. An 11-year-old boy was admitted to hospital because of left
      testicular enlargement, and radical orchiectomy was performed. Macroscopically,
      the tumor was well circumscribed and had a maximum diameter of approximately 2
      cm. The cut surface showed a yellow-white solid mass. Histologically, the tumor
      was composed of large neoplastic cells with abundant eosinophilic cytoplasm with
      a tubular, trabecular, and solid arrangement and loose myxoid stroma with
      irregularly shaped calcification. Immunohistochemically, the tumor cells were
      positive for vimentin, S-100 protein, calretinin, inhibin-alpha, melan-A, and
      CD10, and type IV collagen and laminin were observed in the extracellular matrix
      around the tumor cells. The distributions of melan-A, CD10, and mitochondria were
      characteristically patchy; in contrast, they were diffusely distributed in the
      cytoplasm in a control case of Leydig cell tumor. The differences in
      immunostaining patterns for melan-A, CD10, and mitochondria as well as positivity
      for S-100 protein-beta might be useful diagnostic hallmarks of large cell
      calcifying Sertoli cell tumor for discrimination from Leydig cell tumor.

PMID- 15943796
TI  - Primary mucinous adenocarcinoma of the vagina: possibility of differentiating
      from metastatic adenocarcinomas.
AB  - Primary vaginal adenocarcinomas are rare neoplasms. Herein is reported a case of
      primary vaginal mucinous adenocarcinoma with an interesting mucin profile,
      presumably arising from a lesion of adenosis in a patient without in utero
      exposure to diethylstilbesterol (DES). The patient, a 44-year-old woman, had
      undergone vaginal total hysterectomy 10 years previously for myoma uteri
      corporis. The histological features of the vaginal intramural tumor found in this
      patient resembled those of mucinous adenocarcinoma of the endocervical type.
      Therefore, it was necessary to determine whether or not the tumor was metastatic
      from an occult cervical adenocarcinoma. However, the adenocarcinoma cells of the
      present case did not contain sulfomucin at all, being different from most
      mucinous adenocarcinoma cells of the endocervical type. Moreover, there were foci
      of adenosis adjacent to the adenocarcinoma foci, which also did not contain
      sulfomucin. These findings indicate that the mucinous adenocarcinoma arose from
      vaginal adenosis. Further studies are necessary to investigate whether lack of
      sulfomucin expression is a characteristic feature of vaginal adenosis.

PMID- 15943797
TI  - The small heat shock proteins and their role in human disease.
AB  - Small heat shock proteins (sHSPs) function as molecular chaperones, preventing
      stress induced aggregation of partially denatured proteins and promoting their
      return to native conformations when favorable conditions pertain. Sequence
      similarity between sHSPs resides predominately in an internal stretch of residues
      termed the alpha-crystallin domain, a region usually flanked by two extensions.
      The poorly conserved N-terminal extension influences oligomer construction and
      chaperone activity, whereas the flexible C-terminal extension stabilizes
      quaternary structure and enhances protein/substrate complex solubility. sHSP
      polypeptides assemble into dynamic oligomers which undergo subunit exchange and
      they bind a wide range of cellular substrates. As molecular chaperones, the sHSPs
      protect protein structure and activity, thereby preventing disease, but they may
      contribute to cell malfunction when perturbed. For example, sHSPs prevent
      cataract in the mammalian lens and guard against ischemic and reperfusion injury
      due to heart attack and stroke. On the other hand, mutated sHSPs are implicated
      in diseases such as desmin-related myopathy and they have an uncertain
      relationship to neurological disorders including Parkinson's and Alzheimer's
      disease. This review explores the involvement of sHSPs in disease and their
      potential for therapeutic intervention.

PMID- 15943798
TI  - Molecular mechanisms in successful peripheral regeneration.
AB  - Peripheral nerve injury is normally followed by a robust regenerative response.
      Here we describe the early changes associated with injury from the initial rise
      in intracellular calcium and the subsequent activation of transcription factors
      and cytokines leading to an inflammatory reaction, and the expression of growth
      factors, cytokines, neuropeptides, and other secreted molecules involved in cell
      to-cell communication promoting regeneration and neurite outgrowth. The aim of
      this review is to summarize the molecular mechanisms that play a part in
      executing successful regeneration.

PMID- 15943799
TI  - The yeast stress response. Role of the Yap family of b-ZIP transcription factors.
      The PABMB Lecture delivered on 30 June 2004 at the 29th FEBS Congress in Warsaw.
AB  - The budding yeast Saccharomyces cerevisiae possesses a very flexible and complex
      programme of gene expression when exposed to a plethora of environmental insults.
      Therefore, yeast cell homeostasis control is achieved through a highly
      coordinated mechanism of transcription regulation involving several factors, each
      performing specific functions. Here, we present our current knowledge of the
      function of the yeast activator protein family, formed by eight basic-leucine
      zipper trans-activators, which have been shown to play an important role in
      stress response.

PMID- 15943800
TI  - On the mechanisms of glycolytic oscillations in yeast.
AB  - This work concerns the cause of glycolytic oscillations in yeast. We analyse
      experimental data as well as models in two distinct cases: the relaxation-like
      oscillations seen in yeast extracts, and the sinusoidal Hopf oscillations seen in
      intact yeast cells. In the case of yeast extracts, we use flux-change plots and
      model analyses to establish that the oscillations are driven by on/off switching
      of phosphofructokinase. In the case of intact yeast cells, we find that the
      instability leading to the appearance of oscillations is caused by the
      stoichiometry of the ATP-ADP-AMP system and the allosteric regulation of
      phosphofructokinase, whereas frequency control is distributed over the reaction
      network. Notably, the NAD+/NADH ratio modulates the frequency of the oscillations
      without affecting the instability. This is important for understanding the mutual
      synchronization of oscillations in the individual yeast cells, as synchronization
      is believed to occur via acetaldehyde, which in turn affects the frequency of
      oscillations by changing this ratio.

PMID- 15943801
TI  - Adventitious reactions of alkene monooxygenase reveal common reaction pathways
      and component interactions among bacterial hydrocarbon oxygenases.
AB  - Alkene monooxygenase (AMO) from Rhodococcus rhodochrous (formerly Nocardia
      corallina) B-276 belongs to a family of multicomponent nonheme binuclear iron
      centre oxygenases that includes the soluble methane monooxygenases (sMMOs) found
      in some methane-oxidizing bacteria. The enzymes catalyse the insertion of oxygen
      into organic substrates (mostly hydrocarbons) at the expense of O2 and NAD(P)H.
      AMO is remarkable in its ability to oxidize low molecular-mass alkenes to their
      corresponding epoxides with high enantiomeric excess. sMMO and other well
      characterized homologues of AMO exhibit two adventitious activities: (1) turnover
      dependent inhibition by alkynes and (2) activation by hydrogen peroxide in lieu
      of oxygen and NAD(P)H (the peroxide shunt reaction). Previous studies of the AMO
      had failed to detect these activities and opened the possibility that the
      mechanism of AMO might be fundamentally different from that of its homologues.
      Thanks to improvements in the protocols for cultivation of R. rhodochrous B-276
      and purification and assay of AMO, it has been possible to detect and
      characterize turnover-dependent inhibition of AMO by propyne and ethyne and
      activation of the enzyme by hydrogen peroxide. These results indicate a similar
      mechanism to that found in sMMO and also, unexpectedly, that the enantiomeric
      excess of the chiral epoxypropane product is significantly reduced during the
      peroxide shunt reaction. Inhibition of the oxygen/NADH-activated reaction, but
      not the peroxide shunt, by covalent modification of positively charged groups
      revealed an additional similarity to sMMO and may indicate very similar patterns
      of intersubunit interactions and/or electron transfer in both enzyme complexes.

PMID- 15943802
TI  - Aspartate transcarbamylase from the hyperthermophilic archaeon Pyrococcus abyssi.
      Insights into cooperative and allosteric mechanisms.
AB  - Aspartate transcarbamylase (ATCase) (EC 2.1.3.2) from the hyperthermophilic
      archaeon Pyrococcus abyssi was purified from recombinant Escherichia coli cells.
      The enzyme has the molecular organization of class B microbial aspartate
      transcarbamylases whose prototype is the E. coli enzyme. P. abyssi ATCase is
      cooperative towards aspartate. Despite constraints imposed by adaptation to high
      temperature, the transition between T- and R-states involves significant changes
      in the quaternary structure, which were detected by analytical
      ultracentrifugation. The enzyme is allosterically regulated by ATP (activator)
      and by CTP and UTP (inhibitors). Nucleotide competition experiments showed that
      these effectors compete for the same sites. At least two regulatory properties
      distinguish P. abyssi ATCase from E. coli ATCase: (a) UTP by itself is an
      inhibitor; (b) whereas ATP and UTP act at millimolar concentrations, CTP inhibits
      at micromolar concentrations, suggesting that in P. abyssi, inhibition by CTP is
      the major control of enzyme activity. While V(max) increased with temperature,
      cooperative and allosteric effects were little or not affected, showing that
      molecular adaptation to high temperature allows the flexibility required to form
      the appropriate networks of interactions. In contrast to the same enzyme in P.
      abyssi cellular extracts, the pure enzyme is inhibited by the carbamyl phosphate
      analogue phosphonacetate; this difference supports the idea that in native cells
      ATCase interacts with carbamyl phosphate synthetase to channel the highly
      thermolabile carbamyl phosphate.

PMID- 15943803
TI  - Expression profiling reveals differences in metabolic gene expression between
      exercise-induced cardiac effects and maladaptive cardiac hypertrophy.
AB  - While cardiac hypertrophy elicited by pathological stimuli eventually leads to
      cardiac dysfunction, exercise-induced hypertrophy does not. This suggests that a
      beneficial hypertrophic phenotype exists. In search of an underlying molecular
      substrate we used microarray technology to identify cardiac gene expression in
      response to exercise. Rats exercised for seven weeks on a treadmill were
      characterized by invasive blood pressure measurements and echocardiography. RNA
      was isolated from the left ventricle and analysed on DNA microarrays containing
      8740 genes. Selected genes were analysed by quantitative PCR. The exercise
      program resulted in cardiac hypertrophy without impaired cardiac function.
      Principal component analysis identified an exercise-induced change in gene
      expression that was distinct from the program observed in maladaptive
      hypertrophy. Statistical analysis identified 267 upregulated genes and 62
      downregulated genes in response to exercise. Expression changes in genes encoding
      extracellular matrix proteins, cytoskeletal elements, signalling factors and
      ribosomal proteins mimicked changes previously described in maladaptive
      hypertrophy. Our most striking observation was that expression changes of genes
      involved in beta-oxidation of fatty acids and glucose metabolism differentiate
      adaptive from maladaptive hypertrophy. Direct comparison to maladaptive
      hypertrophy was enabled by quantitative PCR of key metabolic enzymes including
      uncoupling protein 2 (UCP2) and fatty acid translocase (CD36). DNA microarray
      analysis of gene expression changes in exercise-induced cardiac hypertrophy
      suggests that a set of genes involved in fatty acid and glucose metabolism could
      be fundamental to the beneficial phenotype of exercise-induced hypertrophy, as
      these changes are absent or reversed in maladaptive hypertrophy.

PMID- 15943804
TI  - Aly/ REF, a factor for mRNA transport, activates RH gene promoter function.
AB  - The rhesus (Rh) blood group antigens are of considerable importance in
      transfusion medicine as well as in newborn or autoimmune hemolytic diseases due
      to their high antigenicity. We identified a major DNaseI hypersensitive site at
      the 5' flanking regions of both RHD and RHCE exon 1. A 34 bp fragment located at 
      191 to -158 from a translation start position, and containing the TCCCCTCCC
      sequence, was involved in enhancing promoter activity, which was assessed by
      luciferase reporter gene assay. A biotin-labelled 34 bp probe isolated an mRNA
      transporter protein, Aly/REF. The specific binding of Aly/REF to RH promoter in
      erythroid was confirmed by chromatin immunoprecipitation assay. The silencing of
      Aly/REF by siRNA reduced not only the RH promoter activity of the reporter gene
      but also transcription from the native genome. These facts provide second proof
      of Aly/REF as a transcription coactivator, initially identified as a coactivator
      for the TCRalpha enhancer function. Aly/REF might be a novel transcription
      cofactor for erythroid-specific genes.

PMID- 15943805
TI  - Isolation and structural characterization of the Ndh complex from mesophyll and
      bundle sheath chloroplasts of Zea mays.
AB  - Complex I (NADH: ubiquinone oxidoreductase) is the first complex in the
      respiratory electron transport chain. Homologs of this complex exist in bacteria,
      mitochondria and chloroplasts. The minimal complex I from mitochondria and
      bacteria contains 14 different subunits grouped into three modules: membrane,
      connecting, and soluble subcomplexes. The complex I homolog (NADH dehydrogenase
      or Ndh complex) from chloroplasts from higher plants contains genes for two out
      of three modules: the membrane and connecting subcomplexes. However, there is not
      much information about the existence of the soluble subcomplex (which is the
      electron input device in bacterial complex I) in the composition of the Ndh
      complex. Furthermore, there are contrasting reports regarding the subunit
      composition of the Ndh complex and its molecular mass. By using blue native
      (BN)/PAGE and Tricine/PAGE or colorless-native (CN)/PAGE, BN/PAGE and
      Tricine/PAGE, combined with mass spectrometry, we attempted to obtain more
      information about the plastidal Ndh complex from maize (Zea mays). Using
      antibodies, we detected the expression of a new ndh gene (ndhE) in mesophyll (MS)
      and bundle sheath (BS) chloroplasts and in ethioplasts (ET). We determined the
      molecular mass of the Ndh complex (550 kDa) and observed that it splits into a
      300 kDa membrane subcomplex (containing NdhE) and a 250 kDa subcomplex
      (containing NdhH, -J and -K). The Ndh complex forms dimers at 1000-1100 kDa in
      both MS and BS chloroplasts. Native/PAGE of the MS and BS chloroplasts allowed us
      to determine that the Ndh complex contains at least 14 different subunits. The
      native gel electrophoresis, western blotting and mass spectrometry allowed us to
      identify five of the Ndh subunits. We also provide a method that allows the
      purification of large amounts of Ndh complex for further structural, as well as
      functional studies.

PMID- 15943806
TI  - Hemagglutinin-33 of type A botulinum neurotoxin complex binds with synaptotagmin
      II.
AB  - Botulinum neurotoxin type A (BoNT/A), the most toxic substance known to mankind,
      is produced by Clostridium botulinum type A as a complex with a group of
      neurotoxin-associated proteins (NAPs) through polycistronic expression of a
      clustered group of genes. NAPs are known to protect BoNT against adverse
      environmental conditions and proteolytic digestion. Hemagglutinin-33 (Hn-33) is a
      33 kDa subcomponent of NAPs that is resistant to protease digestion, a feature
      likely to be involved in the protection of the botulinum neurotoxin from
      proteolysis. However, it is not known whether Hn-33 plays any role other than the
      protection of BoNT. Using immunoaffinity column chromatography and pull-down
      assays, we have now discovered that Hn-33 binds to synaptotagmin II, the putative
      receptor of botulinum neurotoxin. This finding provides important information
      relevant to the design of novel anti-botulism therapeutic agents targeted to
      block the entry of botulinum neurotoxin into nerve cells.

PMID- 15943807
TI  - A novel transmembrane topology of presenilin based on reconciling experimental
      and computational evidence.
AB  - The transmembrane topology of presenilins is still the subject of debate despite
      many experimental topology studies using antibodies or gene fusions. The results
      from these studies are partly contradictory and consequently several topology
      models have been proposed. Studies of presenilin-interacting proteins have
      produced further contradiction, primarily regarding the location of the C
      terminus. It is thus impossible to produce a topology model that agrees with all
      published data on presenilin. We have analyzed the presenilin topology through
      computational sequence analysis of the presenilin family and the homologous
      presenilin-like protein family. Members of these families are intramembrane
      cleaving aspartyl proteases. Although the overall sequence homology between the
      two families is low, they share the conserved putative active site residues and
      the conserved 'PAL' motif. Therefore, the topology model for the presenilin-like
      proteins can give some clues about the presenilin topology. Here we propose a
      novel nine-transmembrane topology with the C-terminus in the extracytosolic
      space. This model has strong support from published data on gamma-secretase
      function and presenilin topology. Contrary to most presenilin topology models, we
      show that hydrophobic region X is probably a transmembrane segment. Consequently,
      the C-terminus would be located in the extracytosolic space. However, the last C
      terminal amino acids are relatively hydrophobic and in conjunction with existing
      experimental data we cannot exclude the possibility that the extreme C-terminus
      could be buried within the gamma-secretase complex. This might explain the
      difficulties in obtaining consistent experimental evidence regarding the location
      of the C-terminal region of presenilin.

PMID- 15943808
TI  - Formation of nucleoprotein RecA filament on single-stranded DNA. Analysis by
      stepwise increase in ligand complexity.
AB  - RecA protein plays a pivotal role in homologous recombination in Escherichia
      coli. RecA polymerizes on single-stranded (ss) DNA forming a nucleoprotein
      filament. Then double-stranded (ds) DNA is bound and searched for segments
      homologous to the ssDNA. Finally, homologous strands are exchanged, a new DNA
      duplex is formed, and ssDNA is displaced. We report a quantitative analysis of
      RecA interactions with ss d(pN)n of various structures and lengths using these
      oligonucleotides as inhibitors of RecA filamentation on d(pT)20. DNA recognition
      appears to be mediated by weak interactions between its structural elements and
      RecA monomers within a filament. Orthophosphate and dNMP are minimal inhibitors
      of RecA filamentation (I50 = 12-20 mM). An increase in homo-d(pN)2-40 length by
      one unit improves their affinity for RecA (f factor) approximately twofold
      through electrostatic contacts of RecA with internucleoside phosphate DNA
      moieties (f approximately = 1.56) and specific interactions with T or C bases (f
      approximately = 1.32); interactions with adenine bases are negligible. RecA
      affinity for d(pN)n containing normal or modified nucleobases depends on the
      nature of the base, features of the DNA structure. The affinity considerably
      increases if exocyclic hydrogen bond acceptor moieties are present in the bases.
      We analyze possible reasons underlying RecA preferences for DNA sequence and
      length and propose a model for recognition of ssDNA by RecA.

PMID- 15943809
TI  - PKA independent and cell type specific activation of the expression of caudal
      homeobox gene Cdx-2 by cyclic AMP.
AB  - Cdx-2 is a transactivator for the proglucagon gene in pancreatic and intestinal
      endocrine cells. Cdx-2 is also expressed in differentiated intestinal epithelia
      of nonendocrine origin. Cdx-2-/- mice are embryonic lethal, while Cdx-2+/-
      mutants show multiple malfunctions including the formation of intestinal polyps.
      Within the polyps, the remaining wild type Cdx-2 allele ceases its expression,
      while the expression of both Cdx-2 and proglucagon in the endocrine cells remains
      unaltered, indicating that Cdx-2 could be haplo-insufficient for nonendocrine
      cells, but not for proglucagon producing endocrine cells. We propose that
      mechanisms underlying Cdx-2 expression and auto-regulation [Xu F, Li H & Jin T
      (1999), J Biol Chem274, 34310-34316] differ in these two types of cells. We show
      here that forskolin and cAMP upregulate Cdx-2 expression in proglucagon producing
      cells, but not in colon cancer cells and primary intestinal cell cultures. It is
      unlikely that the activation is mainly mediated by PKA, because the activation
      was observed in a PKA deficient cell line. Co-transfecting a dominant negative
      Ras expression plasmid substantially repressed the Cdx-2 promoter, in contrast to
      a previous finding that Ras is a negative factor for Cdx-2 expression in colon
      cancer cells. Furthermore, forskolin activated ERK1/2 phosphorylation in the
      endocrine cells, and attenuation of ERK1/2 phosphorylation by its inhibitor is
      associated with attenuated Cdx-2 expression. Finally, an Epac pathway specific
      cAMP analogue stimulated both ERK1/2 phosphorylation and Cdx-2 expression. Taken
      together, our observations suggest that Cdx-2 expression is regulated by the
      second messenger cAMP, cell-type specifically, via the Epac pathway.

PMID- 15943810
TI  - A natural osmolyte trimethylamine N-oxide promotes assembly and bundling of the
      bacterial cell division protein, FtsZ and counteracts the denaturing effects of
      urea.
AB  - Assembly of FtsZ was completely inhibited by low concentrations of urea and its
      unfolding occurred in two steps in the presence of urea, with the formation of an
      intermediate [Santra MK & Panda D (2003) J Biol Chem278, 21336-21343]. In this
      study, using the fluorescence of 1-anilininonaphthalene-8-sulfonic acid and far
      UV circular dichroism spectroscopy, we found that a natural osmolyte,
      trimethylamine N-oxide (TMAO), counteracted the denaturing effects of urea and
      guanidium chloride on FtsZ. TMAO also protected assembly and bundling of FtsZ
      protofilaments from the denaturing effects of urea and guanidium chloride.
      Furthermore, the standard free energy changes for unfolding of FtsZ were
      estimated to be 22.5 and 28.4 kJ.mol(-1) in the absence and presence of 0.6 M
      TMAO, respectively. The data are consistent with the view that osmolytes
      counteract denaturant-induced unfolding of proteins by destabilizing the unfolded
      states. Interestingly, TMAO was also found to affect the assembly properties of
      native FtsZ. TMAO increased the light-scattering signal of the FtsZ assembly,
      increased sedimentable polymer mass, enhanced bundling of FtsZ protofilaments and
      reduced the GTPase activity of FtsZ. Similar to TMAO, monosodium glutamate, a
      physiological osmolyte in bacteria, which induces assembly and bundling of FtsZ
      filaments in vitro[Beuria TK, Krishnakumar SS, Sahar S, Singh N, Gupta K, Meshram
      M & Panda D (2003) J Biol Chem278, 3735-3741], was also found to counteract the
      deleterious effects of urea on FtsZ. The results together suggested that
      physiological osmolytes may regulate assembly and bundling of FtsZ in bacteria
      and that they may protect the functionality of FtsZ under environmental stress
      conditions.

PMID- 15943811
TI  - A pH-dependent conformational change in EspA, a component of the Escherichia coli
      O157:H7 type III secretion system.
AB  - pH-Dependent structural changes for Escherichia coli O157:H7 EspA were
      characterized by CD, 8-anilino-2-naphthyl sulfonic acid (ANS) fluorescence, and
      sedimentation equilibrium ultracentrifugation. Far- and near-UV CD spectra,
      recorded between pH 2.0 and 7.0, indicate that the protein has significant
      amounts of secondary and tertiary structures. An increase in ANS fluorescence
      intensity (in the presence of EspA) was observed at acidic pH; whereas, no
      increased ANS fluorescence was observed at pH 7.0. These results suggest the
      presence of a partially unfolded state. Interestingly, urea-induced unfolding
      transitions, monitored by far-UV CD spectroscopy, showed that the protein is
      destabilized at pH 2.0 as compared with EspA at neutral pH. Although increased
      ANS fluorescence was observed at pH 3.0, the urea-induced unfolding curve is
      similar to that found at pH 7.0. This result suggests the presence, at pH 3.0, of
      an ordered, but partially unfolded state, which differs from typical molten
      globule. The results of analytical ultracentrifugation and infrared spectroscopy
      indicate that EspA molecules associate at pH 7.0, suggesting the formation of
      short filamentous oligomers containing alpha-helical structures, whereas the
      protein tend to form nonspecific aggregates containing intermolecular beta-sheets
      at pH 2.0. Our experiments indicate that EspA has the potential to spontaneously
      form filamentous oligomers at neutral pH; whereas the protein is partially
      unfolded, assuming different conformations, at acidic pH.

PMID- 15943812
TI  - Comparative analysis of carbohydrate-binding properties of two tandem repeat-type
      Jacalin-related lectins, Castanea crenata agglutinin and Cycas revoluta leaf
      lectin.
AB  - Lectins belonging to the jacalin-related lectin family are distributed widely in
      the plant kingdom. Recently, two mannose-specific lectins having tandem repeat
      type structures were discovered in Castanea crenata (angiosperm) and Cycas
      revoluta (gymnosperm). The occurrence of such similar molecules in taxonomically
      less related plants suggests their importance in the plant body. To obtain clues
      to understand their physiological roles, we performed detailed analysis of their
      sugar-binding specificity. For this purpose, we compared the dissociation
      constants (K(d)) of Castanea crenata agglutinin (CCA) and Cycas revoluta leaf
      lectin (CRLL) by using 102 pyridylaminated and 13 p-nitrophenyl oligosaccharides
      with a recently developed automated system for frontal affinity chromatography.
      As a result, we found that the basic carbohydrate-binding properties of CCA and
      CRLL were similar, but differed in their preference for larger N-linked glycans
      (e.g. Man7-9 glycans). While the affinity of CCA decreased with an increase in
      the number of extended alpha1-2 mannose residues, CRLL could recognize these Man7
      9 glycans with much enhanced affinity. Notably, both lectins also preserved
      considerable affinity for mono-antennary, complex type N-linked glycans, though
      the specificity was much broader for CCA. The information obtained here should be
      helpful for understanding their functions in vivo as well as for development of
      useful probes for animal cells. This is the first systematic approach to
      elucidate the fine specificities of plant lectins by means of high-throughput,
      automated frontal affinity chromatography.

PMID- 15943813
TI  - Autophosphorylation of Archaeoglobus fulgidus Rio2 and crystal structures of its
      nucleotide-metal ion complexes.
AB  - The highly conserved, atypical RIO serine protein kinases are found in all
      organisms, from archaea to man. In yeast, the kinase activity of Rio2 is
      necessary for the final processing step of maturing the 18S ribosomal rRNA. We
      have previously shown that the Rio2 protein from Archaeoglobus fulgidus contains
      both a small kinase domain and an N-terminal winged helix domain. Previously
      solved structures using crystals soaked in nucleotides and Mg2+ or Mn2+ showed
      bound nucleotide but no ordered metal ions, leading us to the conclusion that
      they did not represent an active conformation of the enzyme. To determine the
      functional form of Rio2, we crystallized it after incubation with ATP or ADP and
      Mn2+. Co-crystal structures of Rio2-ATP-Mn and Rio2-ADP-Mn were solved at 1.84
      and 1.75 angstroms resolution, respectively. The gamma-phosphate of ATP is firmly
      positioned in a manner clearly distinct from its location in canonical serine
      kinases. Comparison of the Rio2-ATP-Mn complex with the Rio2 structure with no
      added nucleotides and with the ADP complex indicates that a flexible portion of
      the Rio2 molecule becomes ordered through direct interaction between His126 and
      the gamma-phosphate oxygen of ATP. Phosphopeptide mapping of the
      autophosphorylation site of Rio2 identified Ser128, within the flexible loop and
      directly adjacent to the part that becomes ordered in response to ATP, as the
      target. These results give us further information about the nature of the active
      site of Rio2 kinase and suggest a mechanism of regulation of its enzymatic
      activity.

PMID- 15943814
TI  - FGF-2, IL-1beta and TGF-beta regulate fibroblast expression of S100A8.
AB  - Growth factors, including fibroblast growth factor-2 (FGF-2) and transforming
      growth factor-beta (TGF-beta) regulate fibroblast function, differentiation and
      proliferation. S100A8 and S100A9 are members of the S100 family of Ca2+-binding
      proteins and are now accepted as markers of inflammation. They are expressed by
      keratinocytes and inflammatory cells in human/murine wounds and by appropriately
      activated macrophages, endothelial cells, epithelial cells and keratinocytes in
      vitro. In this study, regulation and expression of S100A8 and S100A9 were
      examined in fibroblasts. Endotoxin (LPS), interferon gamma (IFNgamma), tumour
      necrosis factor (TNF) and TGF-beta did not induce the S100A8 gene in murine
      fibroblasts whereas FGF-2 induced mRNA maximally after 12 h. The FGF-2 response
      was strongly enhanced and prolonged by heparin. Interleukin-1beta (IL-1beta)
      alone, or in synergy with FGF-2/heparin strongly induced the gene in 3T3
      fibroblasts. S100A9 mRNA was not induced under any condition. Induction of S100A8
      in the absence of S100A9 was confirmed in primary fibroblasts. S100A8 mRNA
      induction by FGF-2 and IL-1beta was partially dependent on the mitogen-activated
      protein-kinase pathway and dependent on new protein synthesis. FGF-2-responsive
      elements were distinct from the IL-1beta-responsive elements in the S100A8 gene
      promoter. FGF-2-/heparin-induced, but not IL-1beta-induced responses were
      significantly suppressed by TGF-beta, possibly mediated by decreased mRNA
      stability. S100A8 in activated fibroblasts was mainly intracytoplasmic. Rat
      dermal wounds contained numerous S100A8-positive fibroblast-like cells 2 and 4
      days post injury; numbers declined by 7 days. Up-regulation of S100A8 by FGF-2/IL
      1beta, down-regulation by TGF-beta, and its time-dependent expression in wound
      fibroblasts suggest a role in fibroblast differentiation at sites of inflammation
      and repair.

PMID- 15943815
TI  - The SCO2299 gene from Streptomyces coelicolor A3(2) encodes a bifunctional enzyme
      consisting of an RNase H domain and an acid phosphatase domain.
AB  - The SCO2299 gene from Streptomyces coelicolor encodes a single peptide consisting
      of 497 amino acid residues. Its N-terminal region shows high amino acid sequence
      similarity to RNase HI, whereas its C-terminal region bears similarity to the
      CobC protein, which is involved in the synthesis of cobalamin. The SCO2299 gene
      suppressed a temperature-sensitive growth defect of an Escherichia coli RNase H
      deficient strain, and the recombinant SCO2299 protein cleaved an RNA strand of
      RNA.DNA hybrid in vitro. The N-terminal domain of the SCO2299 protein, when
      overproduced independently, exhibited RNase H activity at a similar level to the
      full length protein. On the other hand, the C-terminal domain showed no CobC-like
      activity but an acid phosphatase activity. The full length protein also exhibited
      acid phosphatase activity at almost the same level as the C-terminal domain
      alone. These results indicate that RNase H and acid phosphatase activities of the
      full length SCO2299 protein depend on its N-terminal and C-terminal domains,
      respectively. The physiological functions of the SCO2299 gene and the relation
      between RNase H and acid phosphatase remain to be determined. However, the
      bifunctional enzyme examined here is a novel style in the Type 1 RNase H family.
      Additionally, S. coelicolor is the first example of an organism whose genome
      contains three active RNase H genes.

PMID- 15943816
TI  - Mg2+-modulated KMnO4 reactivity of thymines in the open transcription complex
      reflects variation in the negative electrostatic potential along the separated
      DNA strands. Footprinting of Escherichia coli RNA polymerase complex at the
      lambdaP(R) promoter revisited.
AB  - There is still a controversy over the mechanism of promoter DNA strand separation
      upon open transcription complex (RPo) formation by Escherichia coli RNA
      polymerase: is it a single or a stepwise process controlled by Mg2+ ions and
      temperature? To resolve this question, the kinetics of pseudo-first-order
      oxidation of thymine residues by KMnO4 in the -11 ... +2 DNA region of RPo at the
      lambdaP(R) promoter was examined under single-hit conditions as a function of
      temperature (13-37 degrees C) in the absence or presence of 10 mm MgCl2. The
      reaction was also studied with respect to thymidine and its nucleotides (TMP, TTP
      and TpT) as a function of temperature and [MgCl2]. The kinetic parameters, (ox)k
      and (ox)E(a), and Mg-induced enhancement of (ox)k proved to be of the same order
      of magnitude for RPo-lambdaP(R) and the nucleotides. Unlike the complex, (ox)E(a)
      for the nucleotides was found to be Mg-independent. The isothermal increase in
      (ox)k with increasing [Mg2+] was thus interpreted in terms of a simple model of
      screening of the negative charges on phosphate groups by Mg2+ ions, lowering the
      electrostatic barrier to the diffusion of MnO4- anions to the reactive double
      bond of thymine. Similar screening isotherms were determined for the oxidation of
      two groups of thymines in RPo at a consensus-like Pa promoter, differing in the
      magnitude of the Mg effect. Together, the findings show that: (a) the two DNA
      strands in the -11...+2 region of RPo-lambdaP(R) are completely separated over
      the whole range of temperatures investigated (13-37 degrees C) in the absence of
      Mg2+ (b) Mg2+ ions induce an increase in the rate of the oxidation reaction by
      screening negatively charged phosphate and carboxylate groups; and (c) the
      observed thymine reactivity and the magnitude of the Mg effect reflect variation
      in the strength of the electrostatic potential along the separated DNA strands,
      in agreement with the current structural model of RPo.

PMID- 15943817
TI  - AcmA of Lactococcus lactis is an N-acetylglucosaminidase with an optimal number
      of LysM domains for proper functioning.
AB  - AcmA, the major autolysin of Lactococcus lactis MG1363 is a modular protein
      consisting of an N-terminal active site domain and a C-terminal peptidoglycan
      binding domain. The active site domain is homologous to that of muramidase-2 of
      Enterococcus hirae, however, RP-HPLC analysis of muropeptides released from
      Bacillus subtilis peptidoglycan, after digestion with AcmA, shows that AcmA is an
      N-acetylglucosaminidase. In the C-terminus of AcmA three highly similar repeated
      regions of 45 amino acid residues are present, which are separated by short
      nonhomologous sequences. The repeats of AcmA, which belong to the lysine motif
      (LysM) domain family, were consecutively deleted, removed, or, alternatively, one
      additional repeat was added, without destroying the cell wall-hydrolyzing
      activity of the enzyme in vitro, although AcmA activity was reduced in all cases.
      In vivo, proteins containing no or only one repeat did not give rise to autolysis
      of lactococcal cells, whereas separation of the producer cells from the chains
      was incomplete. Exogenously added AcmA deletion derivatives carrying two repeats
      or four repeats bound to lactococcal cells, whereas the derivative with no or one
      repeat did not. In conclusion, these results show that AcmA needs three LysM
      domains for optimal peptidoglycan binding and biological functioning.

PMID- 15943818
TI  - Electron transfer chain reaction of the extracellular flavocytochrome cellobiose
      dehydrogenase from the basidiomycete Phanerochaete chrysosporium.
AB  - Cellobiose dehydrogenase (CDH) is an extracellular flavocytochrome containing
      flavin and b-type heme, and plays a key role in cellulose degradation by
      filamentous fungi. To investigate intermolecular electron transfer from CDH to
      cytochrome c, Phe166, which is located in the cytochrome domain and approaches
      one of propionates of heme, was mutated to Tyr, and the thermodynamic and kinetic
      properties of the mutant (F166Y) were compared with those of the wild-type (WT)
      enzyme. The mid-point potential of heme in F166Y was measured by cyclic
      voltammetry, and was estimated to be 25 mV lower than that of WT at pH 4.0.
      Although presteady-state reduction of flavin was not affected by the mutation,
      the rate of subsequent electron transfer from flavin to heme was halved in F166Y.
      When WT or F166Y was reduced with cellobiose and then mixed with cytochrome c,
      heme re-oxidation and cytochrome c reduction occurred synchronously, suggesting
      that the initial electron is transferred from reduced heme to cytochrome c.
      Moreover, in both enzymes the observed rate of the initial phase of cytochrome c
      reduction was concentration dependent, whereas the second phase of cytochrome c
      reduction was dependent on the rate of electron transfer from flavin to heme, but
      not on the cytochrome c concentration. In addition, the electron transfer rate
      from flavin to heme was identical to the steady-state reduction rate of
      cytochrome c in both WT and F166Y. These results clearly indicate that the first
      and second electrons of two-electron-reduced CDH are both transferred via heme,
      and that the redox reaction of CDH involves an electron-transfer chain mechanism
      in cytochrome c reduction.

PMID- 15943819
TI  - Extended half-life upon binding of destabilized intrabodies allows specific
      detection of antigen in mammalian cells.
AB  - The ectopic expression of antibody fragments inside mammalian cells (intrabodies)
      is a challenging approach for probing and modulating target activities. We
      previously described the shuttling activity of intracellularly expressed
      Escherichia coli beta-galactosidase conferred by the single-chain Fv (scFv)
      fragment 13R4 equipped with nuclear import/export signals. Here, by appending to
      scFvs the proteolytic PEST signal sequence (a protein region rich in proline,
      glutamic acid, serine and threonine) of mouse ornithine decarboxylase, we tested
      whether short-lived or destabilized intrabodies could affect the steady-state
      level of target by redirecting it to the proteasomes. In the absence of antigen,
      the half-life of the modified scFv 13R4, relative to untagged molecules, was
      considerably reduced in vivo. However, after coexpression with either cytoplasmic
      or nuclear antigen, the destabilized 13R4 fragments were readily maintained in
      the cell and strictly colocalized with beta-galactosidase. Analysis of
      destabilized site-directed mutants, that were as soluble as 13R4 in the
      intracellular context, demonstrated that binding to antigen was essential for
      survival under these conditions. This unique property allowed specific detection
      of beta-galactosidase, even when expressed at low level in stably transformed
      cells, and permitted isolation by flow cytometry from a transfected cell mixture
      of those living cells specifically labeled with bound intrabody. Altogether, we
      show that PEST-tagged intrabodies of sufficient affinity and solubility are
      powerful tools for imaging the presence and likely the dynamics of protein
      antigens that are resistant to proteasomal degradation in animal cells.

PMID- 15943820
TI  - Experimental proof for a signal peptidase I like activity in Mycoplasma
      pneumoniae, but absence of a gene encoding a conserved bacterial type I SPase.
AB  - Although the annotation of the complete genome sequence of Mycoplasma pneumoniae
      did not reveal a bacterial type I signal peptidase (SPase I) we showed
      experimentally that such an activity must exist in this bacterium, by determining
      the N-terminus of the N-terminal gene product P40 of MPN142, formerly called ORF6
      gene. Combining mass spectrometry with a method for sulfonating specifically the
      free amino terminal group of proteins, the cleavage site for a typical signal
      peptide was located between amino acids 25 and 26 of the P40 precursor protein.
      The experimental results were in agreement with the cleavage site predicted by
      computational methods providing experimental confirmation for these theoretical
      analyses.

PMID- 15943821
TI  - The role of the SEA (sea urchin sperm protein, enterokinase and agrin) module in
      cleavage of membrane-tethered mucins.
AB  - The membrane-tethered mucins are cell surface-associated dimeric or multimeric
      molecules with extracellular, transmembrane and cytoplasmic portions, that arise
      from cleavage of the primary polypeptide chain. Following the first cleavage,
      which may be cotranslational, the subunits remain closely associated through
      undefined noncovalent interactions. These mucins all share a common structural
      motif, the SEA module that is found in many other membrane-associated proteins
      that are released from the cell surface and has been implicated in both the
      cleavage events and association of the subunits. Here we examine the SEA modules
      of three membrane-tethered mucins, MUC1, MUC3 and MUC12, which have significant
      sequence homology within the SEA domain. We previously identified the primary
      cleavage site within the MUC1 SEA domain as FRPG/SVVV a sequence that is highly
      conserved in MUC3 and MUC12. We now show by site-directed mutagenesis that the F,
      G and S residues are important for the efficiency of the cleavage reaction but
      not indispensable and that amino acids outside this motif are probably important.
      These data are consistent with a new model of the MUC1 SEA domain that is based
      on the solution structure of the MUC16 SEA module, derived by NMR spectroscopy.
      Further, we demonstrate that cleavage of human MUC3 and MUC12 occurs within the
      SEA domain. However, the SEA domains of MUC1, MUC3 and MUC12 are not
      interchangeable, suggesting that either these modules alone are insufficient to
      mediate efficient cleavage or that the 3D structure of the hybrid molecules does
      not adequately re-create an accessible cleavage site.

PMID- 15943822
TI  - Clinical relevance of macroprolactin.

PMID- 15943823
TI  - Prevalence of adrenal androgen excess in patients with the polycystic ovary
      syndrome (PCOS).
AB  - OBJECTIVE: To determine the prevalence of adrenal androgen (AA) excess in the
      polycystic ovary syndrome (PCOS) using age- and race-specific normative values.
      DESIGN: Cross-sectional observational study. PATIENTS: One hundred and eight-two
      (88 Black and 94 White) age-matched healthy eumenorrhoeic nonhirsute women
      (controls) and 213 (27 Black and 186 White) women with PCOS were recruited.
      MEASUREMENTS: Total testosterone (T), free T, androstenedione (A4),
      dehydroepiandrosterone sulfate (DHEAS) and SHBG, as well as fasting insulin and
      glucose, were measured in plasma. RESULTS: The mean total T, free T, A4, DHEAS
      and body mass index (BMI) were higher in women with PCOS than in control women.
      DHEAS levels were significantly lower in Black controls than White controls,
      whereas fasting insulin and BMI were higher in Black controls. In control and
      Black PCOS women, DHEAS levels did not correlate with BMI, waist-to-hip ratio
      (WHR) or fasting insulin. Among White women with PCOS, DHEAS levels correlated
      negatively with BMI and fasting insulin. DHEAS levels decreased similarly with
      age in control and PCOS women of either race. For each race and age group the
      upper 95% normative values for log DHEAS was calculated, and the number of PCOS
      subjects with log DHEAS values above this level were assessed. The prevalence of
      supranormal DHEAS levels was 33.3% and 19.9%, respectively, among Black and White
      women with PCOS. CONCLUSIONS: The prevalence of DHEAS excess is approximately 20%
      among White and 30% among Black PCOS patients, when using age- and race-adjusted
      normative values. This study also indicates that the age-associated decline in
      DHEAS levels is observable and similar in both control and PCOS women, regardless
      of race. While BMI and fasting insulin had little impact on circulating DHEAS
      levels in healthy women, among White PCOS patients these parameters were
      negatively associated with circulating DHEAS levels.

PMID- 15943824
TI  - The effect of atorvastatin on serum lipoproteins in acromegaly.
AB  - OBJECTIVE: Acromegaly is associated with long-term adverse effects on
      cardiovascular mortality and morbidity. Reducing growth hormone secretion
      improves well-being and symptoms, but may not significantly improve the
      lipoprotein profile. An additional approach to cardiovascular risk reduction in
      acromegaly may therefore be to target lipoprotein metabolism directly. In this
      study we investigated the effect of statin treatment. DESIGN: Double blind,
      placebo-controlled, crossover study of the effects on circulating lipoproteins of
      atorvastatin 10 mg daily vs. placebo. Each treatment was given for 3 months in
      random order. SUBJECTS: Eleven patients with acromegaly. MEASUREMENTS: Lipids,
      lipoproteins, apolipoproteins, enzyme activity and calculated cardiovascular
      risk. RESULTS: Atorvastatin treatment compared to placebo resulted in a
      significant decrease in serum cholesterol (5.85 +/- 1.04 mmol/l vs. 4.22 +/- 0.69
      mmol/l; mean +/- SD; P < 0.001), low-density lipoprotein (LDL) cholesterol (2.95
      +/- 1.07 mmol/l vs. 1.82 +/- 0.92 mmol/l; P < 0.001), very low-density
      lipoprotein (VLDL) cholesterol (0.31 (0.21-0.47) mmol vs. 0.23 (0.13-0.30) mmol/l
      median (interquartile range); P < 0.05), apolipoprotein B (111 +/- 28 mg/dl vs.
      80 +/- 18 mg/dl; P < 0.001), and calculated coronary heart disease risk (6.8 (3.3
      17.9) vs. 2.8 (1.5-5.7)% over next 10 years; P < 0.01). Serum triglyceride was
      1.34 (1.06-1.71) mmol/l on placebo and 1.14 (0.88-1.48) mmol/l on atorvastatin
      (ns). HDL cholesterol, apolipoprotein A1 and Lp(a) concentrations and cholesteryl
      ester transfer protein and lecithin: cholesterol acyl transferase activities were
      also not significantly altered. CONCLUSION: Atorvastatin treatment was safe, well
      tolerated and effective in improving the atherogenic lipoprotein profile in
      acromegaly.

PMID- 15943825
TI  - The pattern of growth hormone secretion during the menstrual cycle in normal and
      depressed women.
AB  - OBJECTIVE: Major depression is associated to altered hypothalamic-pituitary
      function. Stress is linked to elevated cortisol as well as menstrual cycle
      disturbance; however, there is no known relationship between depression and
      menstrual cycle disruption. The aim of this study was to investigate changes of
      growth hormone (GH) secretion during the menstrual cycle in normal and depressed
      women. DESIGN: Case-control study. PATIENTS AND METHODS: Nineteen women affected
      with depression and 24 normal controls were included. The two groups had
      comparable body mass index (BMI), and age (29.4 +/- 9.8 vs. 28.6 +/- 9.7 years).
      Nine depressed and 10 controls were studied in the follicular phase, while 10
      depressed and 14 controls were studied in the luteal phase of the cycle. GH was
      sampled every 10 min for 24 h, and the data were analysed by the cluster pulse
      detection method. RESULTS: There was no difference in 24-h mean GH concentrations
      between depressed and control subjects (P = 0.93), even after accounting for
      menstrual cycle phase (P = 0.38). GH pulse frequency was higher during the
      follicular phase of the cycle (P = 0.032), and nocturnal GH was higher in the
      follicular phase of the cycle (P = 0.05, and after adjusting for 24-h GH, P =
      0.0138) regardless of whether the subjects were depressed or healthy.
      CONCLUSIONS: In studies of GH secretion in women with or without depression, it
      is necessary to control for the phase of menstrual cycle.

PMID- 15943826
TI  - Morning cortisol does not mediate the association of size at birth with blood
      pressure in children born from full-term pregnancies.
AB  - OBJECTIVE: It had been suggested that programming of the hypothalamo-pituitary
      adrenal axis may underlie the associations of reduced size at birth with raised
      blood pressure in later life. We investigated whether morning salivary cortisol
      mediates the inverse association of birthweight with systolic blood pressure in
      children. DESIGN: Subjects and measurements--a historical cohort study involving
      1152 Swedish children aged 5-14 years, who took part in a family study comprised
      of mother, father, and two full-sibs delivered in 1987-1995 after 38-41 weeks
      gestation within 36 months of each other. Birthweight and gestational age were
      available from obstetric records. Blood pressure, weight, height and puberty
      stage were measured at a clinic. Cortisol was measured by radioimmunoassay in
      morning salivary samples taken at home, within 30 min of waking. RESULTS: Morning
      cortisol showed a weak negative association with length of gestation in siblings,
      was not related to birthweight or to systolic or diastolic blood pressure. There
      was no change in the strength of the negative association between birthweight and
      systolic blood pressure on adjustment for cortisol (-1.4 mmHg/kg, 95% CI -2.7, 
      0.2; adjusted for age, sex, puberty stage, weight and height, and cortisol).
      CONCLUSIONS: Morning cortisol was not associated with size at birth, and did not
      mediate the birthweight-blood pressure association in children born from full
      term pregnancies. It is possible that basal cortisol levels are of more
      importance in explaining associations of size at birth with later blood pressure
      in older subjects, or in populations with more varied length of gestation.
      Alternatively, our results may be caused by misclassification of the hypothalamo
      pituitary-adrenal activity.

PMID- 15943827
TI  - Growth hormone secretion in adult patients with thalassaemia.
AB  - BACKGROUND AND OBJECTIVES: Growth retardation and short stature are frequent
      clinical features of patients with beta-thalassaemia major. Dysfunction of the GH
      IGF-1 axis has been described in many thalassaemic children and adolescents with
      short stature and reduced growth velocity. Several studies have demonstrated that
      recombinant GH treatment improves growth velocity in these patients, although
      response to the treatment is variable and not predictable. A reassessment of the
      GH-IGF-1 axis must be performed in young adults with childhood-onset GH
      deficiency (GHD), after attainment of final height, to select those who are
      candidates for replacement therapy as adults. To our knowledge there are no data
      available on retesting the GH-IGF-1 axis in adult thalassaemic patients with
      childhood-onset GHD. The aim of our study was to investigate GH secretion in
      adult thalassaemic patients with childhood-onset GHD. DESIGN: We reassessed GH
      secretion in a group of adult thalassaemic patients in whom partial GHD had been
      diagnosed during childhood. PATIENTS AND METHODS: We performed an arginine plus
      GH-releasing hormone (GHRH) stimulation test in 16 thalassaemic patients (10
      males, six females) with a mean age of 24.8 +/- 3.6 years. The cut-off level for
      GH response was set at 9 microg/l, according to the literature. Ferritin, IGF-1,
      liver enzymes and lipid levels were also determined. RESULTS: We found persisting
      GHD in three patients, one patient had borderline values (GH peak = 10.4
      microg/l), whereas the others had a normal response. These results are in
      accordance with the data on GH retesting in adult patients with idiopathic
      partial childhood-onset GHD. CONCLUSION: We conclude that GH status should be
      retested in adult thalassaemic patients with childhood-onset GHD. If the
      diagnosis of adult GHD is established, GH treatment may be considered as it could
      contribute to improve heart function and bone mineral density, which are
      frequently impaired in adult thalassaemic patients.

PMID- 15943828
TI  - Decreased type 1 iodothyronine deiodinase expression might be an early and
      discrete event in thyroid cell dedifferentation towards papillary carcinoma.
AB  - OBJECTIVE: Type I iodothyronine deiodinase (D1) catalyses the 5' monodeiodination
      of T4 and is highly expressed in normal human thyroid gland. We have investigated
      D1 expression in a series of benign and malignant differentiated thyroid
      neoplasias. DESIGN: Surgically isolated thyroid tumour fragments were used. D1
      expression was determined by reverse transcription polymerase chain reaction (RT
      PCR) and enzymatic assay. PATIENTS: Tumours and adjacent normal tissues were
      obtained from 28 unselected patients (papillary carcinoma, n = 14; follicular
      adenoma, n = 7; follicular carcinoma, n = 6; anaplastic carcinoma, n = 1).
      MEASUREMENTS: D1 mRNA levels were determined using specific primers for the human
      D1 gene and enzymatic assays were performed using T4 as substrate. RESULTS: In
      papillary thyroid carcinoma (PTC), D1 mRNA and activity levels were decreased
      compared with the surrounding tissue (0.25 +/- 0.24 vs. 1.09 +/- 0.54 arbitrary
      units (AU), P < 0.001 and 0.08 +/- 0.07 vs. 0.24 +/- 0.15 pmol T4/min/mg protein,
      P = 0.045, respectively). Decreased D1 expression was consistent and was observed
      in all histological subtypes and clinical stages analysed, including
      microcarcinomas. By contrast, significantly higher D1 mRNA levels and enzyme
      activity were present in follicular adenoma (1.9 +/- 1.5 vs. 0.83 +/- 0.58 AU, P
      = 0.028 and 2.67 +/- 1.42 vs. 0.22 +/- 0.06 pmol T4/min/mg protein, P = 0.044,
      respectively) and in follicular thyroid carcinoma (FTC) than in surrounding
      normal tissue (1.2 +/- 0.46 vs. 0.67 +/- 0.18 AU, P = 0.038 and 1.20 +/- 0.58 vs.
      0.20 +/- 0.10 pmol T4/min/mg protein, P < 0.001, respectively). Type II
      iodothyronine deiodinase (D2) activity was also significantly higher in
      metastatic FTC samples than in normal thyroid tissues (5.20 +/- 0.81 vs. 0.30 +/-
      0.27 fmol T4/min/mg protein, P < 0.001). CONCLUSIONS: These findings suggest that
      thyroid cell dedifferentiation promotes changes in D1 gene expression by
      pretranscriptional mechanisms and indicate that decreased D1 expression might be
      an early and discrete event in thyroid cell dedifferentiation towards papillary
      thyroid carcinoma.

PMID- 15943829
TI  - Lymphoid tyrosine phosphatase (PTPN22/LYP) variant and Graves' disease in a
      Polish population: association and gene dose-dependent correlation with age of
      onset.
AB  - OBJECTIVE: Susceptibility to Graves' disease (GD) is to a significant extent
      determined by genetic factors of which the best known are those associated with
      the HLA and the CTLA4 locus. Recently, two studies on British Caucasians reported
      that a single nucleotide polymorphism, 1858 C > T in PTPN22, encoding Arg620Trp
      in the lymphoid protein tyrosine phosphatase (LYP), which is a negative regulator
      of T-cell activation, increases the risk of GD. The purpose of our study was to
      investigate whether the PTPN22 'T' allele is associated with GD and/or its
      subsets, defined by clinical or genetic parameters, in a Polish population.
      SUBJECTS AND DESIGN: A cohort of 290 patients and 310 controls was genotyped
      using a PCR-RFLP method. The distribution of PTPN22 alleles and genotypes among
      patients and controls was compared, and correlation was sought between PTPN22 'T'
      and sex, tobacco smoking status, family history of GD, age of disease onset,
      presence (and severity) of ophthalmopathy, and presence of the CTLA4 A49G or
      DRB1*03 alleles. RESULTS: Association between GD and the PTPN22 'T' allele was
      confirmed (OR 1.7, P < 0.0008). Furthermore, a significant correlation between
      the PTPN22 genotype and the age of GD onset was demonstrated (r = -0.18, P =
      0.0019). The PTPN22 'TT' and 'CC' genotypes defined groups characterized by more
      than twofold difference in median age of disease onset (20.8 years vs. 42 years,
      P < 0.003) whereas the 'CT' genotype was associated with an intermediate value
      (35 years). There were no statistically significant correlations with other
      analysed clinical or genetic parameters. CONCLUSIONS: We replicated the
      association between Graves' disease and PTPN22 'T' reported in British
      Caucasians. We also found a gene dose-dependent effect of PTPN22 'T' on the age
      of onset of Graves' disease.

PMID- 15943830
TI  - Higher bone mineral density in Caucasian, hirsute patients of reproductive age.
      Positive correlation of testosterone levels with bone mineral density in
      hirsutism.
AB  - OBJECTIVE: The mechanisms leading to higher bone mineral density (BMD) in hirsute
      patients than in healthy controls have seldom been examined. We compared the
      metabolic, hormonal and bone metabolic parameters in hirsute patients and female
      controls and correlated BMD and bone metabolic parameters with testosterone,
      oestradiol and metabolic parameters. PATIENTS: Fifty-one Caucasian, reproductive
      aged, hirsute patients referred to the outpatient clinic of an academic tertiary
      care medical centre and 63 healthy, female Caucasian controls matched for season,
      weight and age. MEASUREMENTS: BMD (hip, neck, lumbar and total BMD), bone
      metabolic parameters (osteocalcin, alkaline phosphatase, PTH, ionized calcium,
      phosphate and 25-hydroxyvitamin D (25OHD)) and endocrine profiles (androgen
      status, oestradiol and insulin) were evaluated during follicular phase.
      Oestradiol measurement was repeated during cycle days 8-12. RESULTS: Lumbar and
      neck BMD levels were significantly higher in hirsute patients than in controls:
      (mean +/- SD): lumbar BMD 1.10 +/- 0.12 vs. 1.06 +/- 0.10 g/cm2 and neck BMD 0.91
      +/- 0.11 vs. 0.87 +/- 0.12 g/cm2, P < 0.05. Fasting insulin and free testosterone
      levels were significantly higher in hirsute patients than in controls. Free
      testosterone correlated positively with neck and hip BMD levels in hirsute
      patients. During multiple regression analysis, testosterone, oestradiol and
      waist/hip ratio (WHR) were found to have positive effects on BMD levels
      independent of body mass index (BMI). 25OHD levels were significantly lower in
      hirsute patients [42 (13-131)] than in controls [72 (27-196)] nmol/l (geometric
      mean +/- 2SD), P < 0.001]. CONCLUSION: Hirsute patients demonstrated
      significantly higher bone mineral density levels than controls, which could be
      explained by hyperinsulinaemia and higher testosterone levels in hirsute patients
      compared with controls. The pathogenesis for significantly lower 25
      hydroxyvitamin D levels in hirsute patients compared with controls needs to be
      evaluated in future studies.

PMID- 15943831
TI  - Circulating cortisone levels are associated with biochemical markers of bone
      formation and lumbar spine BMD: the Hertfordshire Cohort Study.
AB  - OBJECTIVE: Cortisone is an endogenous corticosteroid that has negligible
      intrinsic glucocorticoid activity but can be converted to the active
      corticosteroid cortisol by the enzyme 11beta-hydroxysteroid dehydrogenase type 1
      (11beta-HSD1). 11beta-HSD1 is expressed in osteoblasts and may play a role in
      determining susceptibility to glucocorticoid-induced osteoporosis. In intact
      osteoblasts enzyme activity, and thus cortisol generation, is dependent on
      substrate concentration with an almost linear increase in activity across the
      physiological range. We have therefore attempted to measure the impact of 11beta
      HSD1 activity on bone in vivo by examining the association of circulating
      cortisone with bone markers, bone mineral density (BMD) and bone loss in a cohort
      of women and men. DESIGN AND SUBJECTS: Baseline cross-sectional association study
      involving 135 women and 171 men aged 61-73 years from the Hertfordshire Cohort
      Study and a 4 year follow-up study examining changes in BMD. MEASUREMENTS: Serum
      cortisone, cortisol and osteocalcin, and urinary type I collagen cross-linked N
      telopeptide (NTX) were measured at baseline. BMD at spine and hip was measured at
      baseline and 4 years later. RESULTS: In men serum cortisone levels were
      negatively correlated with serum osteocalcin (r = -0.20, P = 0.01); a similar
      relationship was seen in women (r = -0.16, P = 0.06). No correlation was seen
      between serum cortisone and urinary NTX (r = 0.03, P = 0.74 for women; r = -0.03,
      P = 0.72 for men). A negative correlation was observed between serum cortisone
      and spine BMD in women (r = -0.18, P = 0.04); a similar relationship was also
      seen in men (r =-0.14, P = 0.07). However, cortisone did not correlate with BMD
      at the femoral neck or total hip or changes in BMD at any site over time. In
      analyses adjusted for adiposity, osteoarthritis grade and a range of life-style
      variables, these relationships did not change substantially. All these
      relationships were independent of cortisol concentrations. CONCLUSIONS: The most
      plausible explanation for the association of circulating cortisone levels with
      osteocalcin is the presence of 11beta-HSD1 activity within osteoblasts. The
      measurement of serum cortisone may independently give insights into the action of
      glucocorticoids on bone.

PMID- 15943832
TI  - Adult growth hormone replacement therapy and neuroimaging surveillance in brain
      tumour survivors.
AB  - OBJECTIVE: Systematic collections of neuroimaging data are nonexistent in brain
      tumour survivors treated with adult growth hormone replacement therapy (AGHRT).
      We present our surveillance data. DESIGN: In 1993, our unit implemented a policy
      of performing brain scans on every brain tumour survivor before starting AGHRT,
      with repeat neuroimaging at least once after 12-18 months' treatment. Reports for
      baseline scans and most recent scans were analysed for this retrospective study.
      PATIENTS: All brain tumour survivors who received AGHRT (60 patients) were
      included in the analysis. MEASUREMENTS: Evidence and extent of residual tumour,
      tumour progression, tumour recurrence, and secondary neoplasms (SN) on baseline
      scan and latest follow-up scan. RESULTS: All patients had baseline scans
      performed. Follow-up scans were available in 41/45 (91%) patients who received
      AGHRT for more than 1 year (mean duration +/- SD of GHRT was 6.7 +/- 3.6 years).
      Sixteen patients had residual tumours, and SNs (all meningiomas) were
      demonstrated in three patients on baseline scans. Appearances remained stable in
      34 (83%) patients during follow-up (extending to 17.4 +/- 8.3 years after tumour
      diagnosis). Of the 16 residual primary tumours, an incurable ependymoma continued
      to grow, and one meningioma progressed slightly in size over 7.7 years. Follow-up
      scans also revealed continued growth of the SNs detected at baseline, and five
      additional meningiomas (two in patients with a previous SN, confirming an excess
      risk in this subgroup, P = 0.02). All SNs occurred on average 22.8 (range 17-37)
      years after radiotherapy. CONCLUSIONS: Our data do not suggest an increased rate
      of recurrence or progression of childhood brain tumours during AGHRT.
      Nonetheless, vigilance and long-term surveillance are needed in these patients in
      order to detect and monitor SNs, in particular in patients with a previous
      history of a SN. We endorse a proactive neuroimaging policy, preferably as part
      of a larger, controlled trial in the future.

PMID- 15943833
TI  - The effects of 12 months of growth hormone replacement therapy on cardiac
      autonomic tone in adults with growth hormone deficiency.
AB  - OBJECTIVES: Growth hormone deficiency (GHD) in adults is associated with a
      cluster of cardiovascular risk factors. Some abnormalities of cardiac structure
      and function have been reported in adult patients with GHD, but there are few
      data related to cardiac autonomic tone. Non-invasive assessment of cardiac
      autonomic status can be achieved by heart rate variability (HRV), which can be
      measured by using time-domain or frequency-domain variables. To our knowledge,
      short-term (6 months) effects of GH replacement therapy (GHRT) on HRV in a
      limited number of patients have been evaluated prospectively in only two previous
      studies. The present study was therefore designed to investigate the effects of
      GHD and 12 months of GHRT on cardiac autonomic tone in a larger number of adult
      patients with severe GHD. PATIENTS AND METHODS: HRV measurement, by using time
      domain variables, was performed in 22 patients with GHD (eight men, 14 women;
      mean age 45.4 +/- 2.4 years) and 22 healthy controls (nine men, 13 women; mean
      age 40.8 +/- 1.8 years) at baseline. The time-domain variables (sympathetically
      influenced parameters SDNN and SDANN and parasympathetically influenced
      parameters RMSSD and PNN50) were derived from 24-h electrocardiogram (ECG)
      recordings. In the patient group, cardiac autonomic tone was re-evaluated after 6
      and 12 months of GHRT. RESULTS: Mean baseline values of SDNN and SDANN were
      significantly higher (higher values mean lower sympathetic activity) in GHD
      patients than in healthy controls (P < 0.05), but mean baseline values of RMSSD
      and PNN50 did not differ significantly in healthy controls and patients. After 6
      and 12 months of GHRT, mean SDNN and SDANN were decreased significantly when
      compared with the baseline values before GHRT (P < 0.05). However, mean RMSSD and
      PNN50 did not differ significantly from baseline. When SDNN and SDANN
      measurements were evaluated individually for each patient, after 12 months of
      GHRT both of the sympathetically influenced parameters decreased in 90% of the
      patients. CONCLUSIONS: These data indicate that sympathetic tone is decreased in
      adult patients with severe GHD. Additionally, an increment in sympathetic
      activity and normalization of sympathovagal balance have been demonstrated after
      6 and 12 months of GHRT. This result suggests that, at least at the doses used in
      this study, GHRT improves sympathetic tone, without an obvious arrhythmogenic
      effect.

PMID- 15943834
TI  - A population study of the association between thyroid autoantibodies in serum and
      abnormalities in thyroid function and structure.
AB  - OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with
      goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known
      about the prevalence of subclinical autoimmune hypothyroidism. The aims of this
      study were to evaluate the association between thyroid autoantibodies in serum
      and abnormalities in thyroid function and structure, and to study the thyroid
      volume in subjects with subclinical autoimmune hypothyroidism. DESIGN: A
      population study including 4649 randomly selected subjects. MEASUREMENTS: Blood
      tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab),
      thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. RESULTS: Thyroid volume
      was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and
      large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%.
      Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (>
      3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was
      0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a
      strong association between large volume and autoantibodies, but only in subjects
      with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab
      in univariate analyses (P < 0.001) was due to confounding by sex and age
      (multivariate model, P = 0.23). CONCLUSION: We identified a subgroup of the
      population with subclinical goitrous Hashimoto's disease and a smaller subgroup
      with subclinical autoimmune atrophic thyroiditis. This relationship between small
      and large thyroid volume in subclinical disease is opposite to that in overt
      disease, which may suggest that the period between development of a small volume
      with circulating autoantibodies and overt hypothyroidism is relatively short.

PMID- 15943835
TI  - Overproduction of an amino-terminal form of PTH distinct from human PTH(1-84) in
      a case of severe primary hyperparathyroidism: influence of medical treatment and
      surgery.
AB  - OBJECTIVE: Rare patients with severe primary hyperparathyroidism present with
      large parathyroid tumours, severe hypercalcaemia, very high PTH levels and
      osteitis fibrosa cystica. Some of these patients display a large amount of C-PTH
      fragments in circulation and present with a higher C-PTH/I-PTH ratio than seen in
      less severe cases of primary hyperparathyroidism. We wanted to determine how PTH
      levels and circulating PTH high-performance liquid chromatography (HPLC) profiles
      analysed with PTH assays having different epitopes could be affected by medical
      and surgical treatment in such patients. DESIGN: A 55-year-old man with severe
      hypercalcaemia (Ca(2+): 2.01 mmol/l), very high PTH levels (CA-PTH 82.1 and T-PTH
      72 pmol/l) caused by a large parathyroid tumour (7.35 g) and accompanied by
      significant bone involvement (alkaline phosphatase of 185 UI/l and subperiostal
      bone resorption of hands) was referred to us. Blood was obtained at various time
      points during his medical treatment, before and after surgery, to measure
      parameters of calcium and phosphorus metabolism, and of bone turnover. HPLC
      separations of circulating PTH molecular forms were performed and analysed with
      PTH assays having 1-4 (CA), 12-18 (T), 26-32 (E) and 65-84 (C) epitopes. RESULTS:
      Before surgery, serum Ca2+ was nearly normalized with hydratation, intravenous
      (IV) pamidronate and oral vitamin D administration. Despite a decrease in Ca2+ to
      1.31 mmol/l, CA-PTH and T-PTH levels decreased by half in relation to a threefold
      increase in basal 1,25-dihydroxyvitamin D [1,25(OH)2D] level (94 to 337 pmol/l).
      After this initial positive response, hypercalcaemia and elevated CA- and T-PTH
      levels recurred even if 1,25(OH)2D levels remained elevated. The tumour was
      removed surgically and proved to be poorly differentiated with nuclear atypia and
      mitosis. After surgery, the Ca2+ level and PTH secretion normalized. The higher
      CA-PTH level relative to the T-PTH level observed before surgery in this patient
      was related to the oversecretion of an amino-terminal (N) form of PTH recognized
      by PTH assays with (1-4) or (26-32) epitopes but not by the T-PTH assay with a
      (12-18) epitope. This molecular form represented 50% of CA-PTH measured in this
      patient, but only 7% in less severe cases of primary hyperparathyroidism. It was
      unaffected by medical therapy and disappeared after surgery. CONCLUSION: The
      relationship between the overexpression of this N-PTH molecular form and severe
      primary hyperparathyroidism remains unclear. Further studies will be required in
      these rare patients to see whether N-PTH is a marker of less well differentiated
      parathyroid tumours and/or relates to the overproduction of C-PTH fragments in
      the presence of severe hypercalcaemia.

PMID- 15943836
TI  - Could associations between breastfeeding and insulin-like growth factors underlie
      associations of breastfeeding with adult chronic disease? The Avon Longitudinal
      Study of Parents and Children.
AB  - OBJECTIVE: The influence of infant feeding method (breast/formula) on growth
      factor levels could underlie associations of breastfeeding with childhood growth
      and risk factors for cardiovascular disease. We investigated associations of
      having been breastfed with serum IGF-I and IGFBP-3 in childhood. METHODS:
      Prospective birth cohort study (subsample of the Avon Longitudinal Study of
      Parents and Children, UK) based on 871 children born in 1991/1992 who underwent
      clinical follow-up and blood tests at age 7-8 years. A total of 488 (56%)
      children had complete data. RESULTS: In children with complete data, the age- and
      sex-standardized IGF-I levels of those who were partially or exclusively
      breastfed were 6.1 and 13.8 ng/ml higher, respectively, than those who were never
      breastfed (increase in IGF-I levels per category of breastfeeding exclusivity:
      7.1 ng/ml; 95% CI: 0.3-13.9; P = 0.04). In models also controlling for
      birthweight, gestational age, mother's age, and socioeconomic and dietary
      factors, the breastfeeding-IGF-I association was attenuated (regression
      coefficient: 3.3 ng/ml; -4.2-10.7; P = 0.4); further adjustment for IGFBP-3 made
      little difference (regression coefficient: 4.1 ng/ml; -2.8-10.9; P = 0.2). There
      was little evidence for an association between breastfeeding and IGFBP-3 or the
      molar ratio IGF-I/IGFBP-3. CONCLUSIONS: The positive association between
      breastfeeding and IGF-I could be due to residual confounding or to chance.
      Nevertheless, the magnitude of the fully adjusted effect estimate and the novelty
      of the association suggest that larger studies should now be conducted to confirm
      or refute the hypothesis that variations in IGF-I by infant feeding mode explain
      associations of breastfeeding with health in later life.

PMID- 15943837
TI  - Relationship between fasting serum glucose, age, body mass index and serum 25
      hydroxyvitamin D in postmenopausal women.
AB  - OBJECTIVE: Because it has been reported that vitamin D, given to mother or
      infant, can prevent type I diabetes in children, that diabetes is more common in
      adults with low serum vitamin D and that insulin secretion and action are related
      to vitamin D levels in healthy young adults we examined the relationship between
      serum vitamin D metabolites and fasting serum glucose in patients attending our
      outpatient clinics. DESIGN: Retrospective examination of convenience sample of
      postmenopausal women attending our osteoporosis clinics. PATIENTS: A total of 753
      postmenopausal women attending a university hospital outpatient clinic and not on
      any treatment known to affect glucose metabolism. MEASUREMENTS: Body weight and
      height, serum 25-hydroxyvitamin D [25(OH)D], serum 1,25-dihydroxyvitamin D
      [1,25(OH)2D], serum PTH and fasting serum glucose. RESULTS: On simple correlation
      fasting serum glucose was a positive function of age (P < 0.05), weight (P <
      0.001) and body mass index (BMI) (P < 0.001) and a negative function of serum
      25(OH)D (P < 0.001), but it was not significantly related to either serum
      1,25(OH)2D, PTH or creatinine. When fasting serum glucose was regressed
      simultaneously on age, BMI and 25(OH)D, glucose was still an inverse function of
      25(OH)D (P = 0.006). CONCLUSIONS: Fasting serum glucose increased as 25(OH)D
      levels fell throughout the range of serum 25(OH)D measured but the greatest
      increase was observed in those with 25(OH)D below 40 nmol/l.

PMID- 15943838
TI  - The nadir growth hormone after an octreotide test dose predicts the long-term
      efficacy of somatostatin analogue therapy in acromegaly.
AB  - OBJECTIVE: In the treatment of acromegaly, a 'test dose' of octreotide is
      recommended prior to the use of depot somatostatin analogue (SSA) therapy.
      However, there remains no consensus regarding the criteria that predict a
      response to treatment. The ability to select patients who may benefit most from
      medical therapy is potentially of great value in clinical practice. The aim of
      the study was to determine the predictive value of both the nadir GH and the mean
      GH following an octreotide test dose in identifying patients who subsequently
      achieved disease remission with depot SSA therapy. Remission was defined as a
      mean GH < 5 mU/l (< 2 microg/l). DESIGN: Retrospective case-control study.
      PATIENTS: A group of 41 patients with acromegaly underwent an octreotide test
      dose where GH was measured hourly for a total of 6 h following an injection of
      octreotide 50 microg subcutaneously. Nadir GH and mean GH following the
      octreotide test dose were determined. Thirty-three patients were subsequently
      treated with depot SSA therapy and mean GH and IGF-I levels were determined at
      follow-up. RESULTS: The nadir GH demonstrated superior predictive power to that
      of mean GH across a range of GH cut-off values. A nadir GH < 5 mU/l demonstrated
      80% sensitivity and 83% specificity in predicting remission with depot SSA
      therapy. A nadir GH < 10 mU/l demonstrated 100% sensitivity and 56% specificity.
      CONCLUSIONS: The nadir GH following an octreotide test dose is a useful
      predictive marker of achieving disease remission with depot SSA therapy used as
      either a primary or an adjuvant agent.

PMID- 15943840
TI  - Efficacy of famotidine and omeprazole in healing symptoms of non-erosive gastro
      oesophageal reflux disease: randomized-controlled study of gastro-oesophageal
      reflux disease.
AB  - BACKGROUND: The epidemiology and pathophysiology of non-erosive gastro
      oesophageal reflux disease differs from erosive gastro-oesophageal reflux
      disease. There is a possibility that non-erosive gastro-oesophageal reflux
      disease treatment requires a different regimen/approach but it is not yet
      acknowledged. AIM: To investigate the efficacy of famotidine and omeprazole in
      the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro
      oesophageal reflux disease. PATIENTS AND METHODS: A randomized, open-label trial
      was conducted. Fifty-four gastro-oesophageal reflux disease patients were
      assigned to treatment with famotidine at a dosage of 20 mg twice daily; or
      omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health
      Survey and Gastrointestinal Symptom Rating Scale administered at baseline and
      after 8 weeks of treatment as well as a symptom questionnaire were conducted
      daily. RESULTS: Short Form-36 revealed that gastro-oesophageal reflux disease has
      severe impact on health-related quality of life. Thirty-nine subjects (77%) were
      endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The
      mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score
      of non-erosive gastro-oesophageal reflux disease significantly improved in
      famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no
      significant change regarding improved heartburn symptoms of non-erosive gastro
      oesophageal reflux disease between treatments in the daytime or night-time.
      CONCLUSION: Famotidine and omeprazole were both effective in improving symptoms
      of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal
      reflux disease.

PMID- 15943841
TI  - Famotidine vs. omeprazole: a prospective randomized multicentre trial to
      determine efficacy in non-erosive gastro-oesophageal reflux disease.
AB  - BACKGROUND: Several studies in Western countries showed that proton-pump
      inhibitors are superior to histamine2-receptor antagonists or placebo in the
      treatment of non-erosive gastro-oesophageal reflux disease. The efficacy of acid
      suppressive drugs for non-erosive gastro-oesophageal reflux disease in Japan, in
      which the prevalence of Helicobacter pylori infection is higher compared with
      Western countries, is unknown. AIM: To compare the efficacy of famotidine and
      omeprazole in Japanese patients with non-erosive gastro-oesophageal reflux
      disease by a prospective randomized multicentre trial. METHODS: A total of 98
      patients received either famotidine 20 mg b.d. (n = 48) or omeprazole once daily
      (n = 50). Frequency of gastro-oesophageal reflux disease symptoms and health
      related quality of life were evaluated at baseline and after 4 weeks of
      treatment. Complete relief was defined as no gastro-oesophageal reflux disease
      symptoms during the 7-day interval in week 4. RESULTS: Complete relief was
      achieved in 23 (48%) of patients receiving famotidine and 28 (56%) of patients
      treated with omeprazole. In the famotidine group, complete relief rate in H.
      pylori-negative patients was significantly lower than H. pylori-positive patients
      (35% vs. 64%). Both famotidine and omeprazole improved most scales of health
      related quality of life. Omeprazole significantly improved reflux score
      irrespective of H. pylori infection while famotidine significantly improved
      reflux score in H. pylori-positive patients but not in H. pylori-negative
      patients. CONCLUSIONS: Omeprazole is more effective than famotidine for the
      control of gastro-oesophageal reflux disease symptoms in H. pylori-negative
      patients, while similar efficacy is observed in H. pylori-positive patients with
      non-erosive gastro-oesophageal reflux disease.

PMID- 15943842
TI  - Minimal change oesophagitis: a disease with characteristic differences to erosive
      oesophagitis.
AB  - BACKGROUND: The majority of gastro-oesophageal reflux disease (GERD) seems to be
      non-erosive reflux disease. Nonerosive reflux disease includes minimal change
      oesophagitis (whitish or reddish, oedematous change and erosion that is not
      regarded as mucosal break) and no endoscopic abnormalities. AIM: To investigate
      the accurate proportion of those with minimal change oesophagitis and to clarify
      its characteristics. In addition, we evaluated the effect of famotidine (40
      mg/day) in those with minimal change. METHODS: Prospective endoscopic assessment
      was performed for consecutive 606 out-patients. Of the 582 patients suitable for
      analysis, 347 were non-treated. The latter were divided into those with erosive
      GERD or minimal change, and their endoscopic findings and characteristics were
      compared. RESULTS: Among 347 non-treated patients, 88 (25%) had erosive GERD and
      249 (72%) had minimal change. Compared with patients who have erosive GERD and
      those with minimal change, the latter were less likely to have hiatal hernia or
      bile reflux, but more likely to have gastric atrophy. Symptomatic patients (n =
      55) with minimal change oesophagitis were more likely to have hiatal hernia than
      those who were asymptomatic (n= 194). Most patients preferred taking famotidine
      on-demand, during a 4-week follow-up period. CONCLUSIONS: Most non-erosive reflux
      disease can be classified as minimal change oesophagitis, and that have different
      characteristics from erosive GERD. On-demand famotidine may be a suitable
      alternative treatment for patients with minimal change disease.

PMID- 15943843
TI  - Randomized, double-blind, placebo-controlled crossover trial of famotidine in
      patients with functional dyspepsia.
AB  - BACKGROUND: Histamine 2-receptor antagonists were used as a first therapy against
      functional dyspepsia. However, few clinical studies with famotidine for
      functional dyspepsia have been reported. AIM: To evaluate the effectiveness of
      famotidine for functional dyspepsia patients. METHODS: A multicentre, randomized,
      double-blind, placebo-controlled crossover trail was conducted. Patients
      diagnosed with functional dyspepsia by the Roma II criteria were included.
      Subjects were randomized into two groups, and received either famotidine or
      placebo as the first 4 weeks medication. After a 1-week washout period, they were
      switched to the other regimen for another 4 weeks. Evaluation was made prior to
      the start of study, upon completion of the first drug cycle, and the second drug
      cycle, by Gastrointestinal Symptoms Rating Scale for the seriousness of abdominal
      symptoms, and by Short Form-36 for the level of quality of life. RESULTS:
      Nineteen of 21 enrolled patients successfully completed this study. Significant
      improvement in Gastrointestinal Symptoms Rating Scale scores was observed in
      abdominal pain (P = 0.007), indigestion and reflux syndrome after famotidine
      treatment. Also quality of life scores showed significant improvement in body
      pain, vitality and general health perceptions after famotidine treatment. There
      was no improvement of symptoms and quality of life scores after administration of
      placebo. CONCLUSIONS: Famotidine was effective for improving symptoms and quality
      of life in functional dyspepsia patients.

PMID- 15943844
TI  - Usefulness of famotidine in functional dyspepsia patient treatment: comparison
      among prokinetic, acid suppression and antianxiety therapies.
AB  - BACKGROUND: The treatment of functional dyspepsia is controversial. AIM: The
      purpose of this paper is to clarify the initial effect of prokinetic, acid
      suppression and antianxiety treatment for functional dyspepsia patients. PATIENTS
      AND METHODS: Sixty-four functional dyspepsia patients without Helicobacter pylori
      infection were randomly assigned to 15 mg/day of mosapride, 40 mg/day of
      famotidine, or 30 mg/day of tandospirone during an 8-week treatment. Individual
      functional dyspepsia symptoms were evaluated with 4 cm visual analogue scale
      before and at 2, 4 and 8 weeks after treatment. RESULTS: Among 64 enrolled
      patients, 62 completed the study. Within 2 weeks, visual analogue scale score in
      the mosapride-treated group decreased from 2.29 +/-0.14 to 1.57 +/- 0.20; in the
      famotidine from 2.04 +/- 0.16 to 1.09 +/- 0.12 (mean +/- S.E.). Therefore, there
      were significant improvements of functional dyspepsia symptoms in mosapride- and
      famotidine-treated patients (P <0.01). Furthermore, famotidine was significantly
      more effective than mosapride (P < 0.05). On the contrary, visual analogue scale
      score in the tandospirone therapy was 2.23 +/- 0.20 and 2.13 +/- 0.22 before and
      at 2 weeks, respectively, without any significant improvement. CONCLUSIONS: A
      treatment regimen of famotidine at 40 mg/day had a significant favourable effect
      on the clinical outcome in functional dyspepsia patients.

PMID- 15943845
TI  - Effects of famotidine, mosapride and tandospirone for treatment of functional
      dyspepsia.
AB  - BACKGROUND: An effective therapeutic strategy for functional dyspepsia (FD) has
      not been well-established. AIM: We investigated and compared the therapeutic
      effects of famotidine, mosapride and tandospirone for the control of dyspeptic
      symptoms. METHODS: Fully examined FD patients of outpatient clinics at seven
      different medical centres were enrolled in the study. They were randomly assigned
      to three groups based on the type of drug administered: famotidine, mosapride and
      tandospirone. The effects of treatment over 4 weeks were assessed by visual
      analogue scales. RESULTS: All of the drugs showed beneficial effects, although
      famotidine was the most effective for symptom relief, which was significantly
      greater than tandospirone, while the effect of mosapride was similar to that of
      famotidine. No subtype of FD showed a better response to a particular type of
      drug. CONCLUSIONS: For the treatment of FD, famotidine demonstrated the best
      therapeutic effect, followed by mosapride, while that of tandospirone was
      significantly lower.

PMID- 15943846
TI  - New strategy of therapy for functional dyspepsia using famotidine, mosapride and
      amitriptyline.
AB  - BACKGROUND: In functional gastrointestinal (GI) disorders including functional
      dyspepsia (FD) and irritable bowel syndrome (IBS), there might be no small extent
      of contributions of psychosomatic factors. As a therapy for IBS patients, the
      effectiveness of antidepressants has been reported. AIM: In this study, we
      evaluated the efficacy of H2-receptor antagonist (famotidine) and 5-HT4 receptor
      agonist (mosapride citrate). In addition, the effect of antidepressants was
      assessed as the second-step therapy. METHODS: Patients complaining upper GI
      symptoms were diagnosed as FD excluding organic diseases. Randomized patients
      received 20 mg/day of famotidine or 15 mg/day of mosapride citrate for 4 weeks
      and the efficacy was compared between the two groups based on a 10-point visual
      analogue scale. When symptoms were not relieved (score improvement 0-2 points),
      patients received amitriptyline (30 mg/day) or no medication for 4 weeks
      randomly. Patients who had depression in psychological test (SDS) were omitted.
      RESULTS: As the first-step therapy, both famotidine and mosapride showed
      beneficial effects regardless of FD subtypes, age and gender. The efficacy of
      these two drugs in relieving FD symptoms was not significantly different. In
      patients who failed in the first-step therapy, amitriptyline showed beneficial
      effects. CONCLUSIONS: These findings might be clinically important in view of the
      efficient relief of symptoms in FD patients.

PMID- 15943847
TI  - Primary care in the treatment of functional gastrointestinal symptoms in Japan:
      prescription preferences and impression of results.
AB  - BACKGROUND: Functional gastrointestinal (GI) disorders are common in primary
      care. However, proper pharmacological approaches have not yet been established.
      The reason for a lack of proper approaches may be attributable to the lack in
      clarity of their pathogenesis and pathophysiology. Meta-analysis of
      pharmacological approaches to functional GI disorders failed to identify the
      solid cluster of patients' symptoms. AIM: The aim of this study is to assess the
      perspective of primary care doctors concerning prescriptions for functional GI
      symptoms, evaluate the efficacy of the drugs prescribed, and the need for
      medication for these symptoms. METHOD: Questionnaires were sent to primary care
      doctors, and a total of 149 responses were obtained. Efficacy of each medication
      was evaluated by the number of doctors favouring the category, and the respective
      impressions of prescriptions given. RESULTS: Symptoms of heartburn were well
      controlled by anti-secretory drugs (H2RAs and PPIs), while appetite loss and
      abdominal gurgling were not controlled by any medications. CONCLUSIONS: This
      survey reveals differences in need for various prescription drugs in functional
      GI symptoms.

PMID- 15943848
TI  - Famotidine prevents canine gastric blood flow reduction by NSAIDs.
AB  - AIM: To investigate the effect of famotidine on gastric blood flow reduction
      induced by diclofenac sodium, a common non-steroidal anti-inflammatory drug in
      Japan, using laser Doppler flowmetry in the canine stomach. METHODS: The gastric
      mucosal blood flow was measured by laser Doppler flowmetry in 15 healthy male
      beagles before and 60 min after the administration of diclofenac suppository (1.0
      mg/kg) into the rectum. The examination was done in a crossover, single-blinded
      fashion. All dogs underwent both famotidine (0.5 mg/kg) and placebo (saline)
      injection simultaneously with the administration of diclofenac. In addition, the
      tissue concentration of prostaglandin E2 was measured. RESULTS: The blood flow
      decreased by 18.3 +/- 9.1% in the gastric body, by 26.3 +/- 8.1% in the antrum in
      the placebo group after the administration of diclofenac sodium, while the
      decreases seen were significantly smaller in the famotidine group: 3.2 +/- 12.6%
      in the gastric body and 7.9 +/- 16.5% in the antrum (P = 0.001 for the gastric
      body, P = 0.0034 for the antrum). Conversely, the percentage of mucosal
      prostaglandin E2 concentration decrease in each group did not show a significant
      difference. CONCLUSION: Famotidine alleviates the reduction of gastric blood flow
      induced by diclofenac sodium. Further, not only mucosal prostaglandins but also
      gastric acid may play an important role in non-steroidal anti-inflammatory drugs
      induced gastric microcirculatory disturbance.

PMID- 15943849
TI  - A clinical study of Japanese patients with ulcer induced by low-dose aspirin and
      other non-steroidal anti-inflammatory drugs.
AB  - BACKGROUND: The incidence and severity of non-steroidal anti-inflammatory drugs
      (NSAIDs)-induced gastro-duodenal ulcer have not been extensively studied in
      Japan. AIM: We performed a prospective study to clarify NSAIDs-induced gastro
      duodenal injury, focusing especially on low-dose aspirin (L-A). METHODS: Two
      hundred and thirty-eight patients with bleeding peptic ulcers admitted to our
      hospital. History of taking NSAIDs and anti-ulcer drugs was obtained from all
      patients who underwent endoscopic examinations. The lesion scores of patients
      taking L-A were classified numerically from zero (no lesion) to five (ulcer).
      RESULTS: The NSAIDs were associated with 28.2% of hemorrhagic ulcers. The rates
      of patients using L-A, loxoprofen, diclofenac, and combination of two of these
      drugs were 27, 16, 10 and 9%, respectively. Co-administered anti-ulcer drugs were
      cytoprotective anti-ulcer drugs (27%), H2 receptor antagonists (16%), PPI (4%),
      and none (53%). In patients taking L-A, H2 receptor antagonists were used most
      frequently. The HP was positive in 63% of L-A-induced ulcer cases and in 69% of
      NSAIDs other than low-dose aspirin-induced ulcer cases. The lesion scores of
      patients taking L-A with H2 receptor antagonists or PPI were significantly lower
      than those of patients who were taking only L-A (P < 0.05). CONCLUSIONS:
      Approximately one-third of hospitalized patients with NSAIDs-induced hemorrhagic
      ulcer showed an association with L-A. Prospective randomized controlled trials
      including H2 receptor antagonists are required to establish preventive efforts
      aimed at L-A-induced gastro-duodenal injury.

PMID- 15943850
TI  - Preventive therapy for non-steroidal anti-inflammatory drug-induced ulcers in
      Japanese patients with rheumatoid arthritis: the current situation and a
      prospective controlled-study of the preventive effects of lansoprazole or
      famotidine.
AB  - BACKGROUND: There is a lack of evidence for the efficacy of preventive
      medications for peptic ulcers (PUs) among long-term users of non-steroidal anti
      inflammatory drugs (NSAIDs) in Japan. AIM: To estimate the preventive effect by
      normal dose, not high-dose histamine-H2 receptor antagonists (H2RA) for NSAID
      induced ulcers. METHODS: We designed two different studies to assess the efficacy
      of anti-ulcer agents in rheumatoid arthritis (RA) in patients treated over a long
      term with NSAIDs. An investigative survey divided patients into those not taking
      anti-ulcer agents (non-medication group); those taking mucosal protective agents
      (mucosal protectant group), H2RA (H2RA group), proton pump inhibitors (PPI
      group), or a prostaglandin E1 analog (PG) (PG group). The second study compared
      prospectively the preventive effects of either famotidine 20 mg bd (famotidine
      group) or lansoprazole 15 mg daily (lansoprazole group) in patients with PU
      scars. RESULTS: The prevalence of PU in the H2RA group was significantly lower
      compared to the mucosal protectant group (P < 0.05), and the mucosal protectant
      group was not significantly different to the non-medication group. The
      prospective study revealed that the PU onset rate of the famotidine group was 8%
      (1/13), and lansoprazole group was 15% (2/13), indicating no significant
      differences between the two. CONCLUSIONS: In Japan, normal-dose H2RA is expected
      to be a new PU preventive treatment strategy in patients requiring long-term
      NSAID therapy.

PMID- 15943851
TI  - Effect of famotidine on recurrent bleeding after successful endoscopic treatment
      of bleeding peptic ulcer.
AB  - AIM: We investigated the effect of acid suppression therapy on recurrent bleeding
      after successful endoscopic treatment of bleeding peptic ulcer. METHODS: A total
      of 400 patients with bleeding peptic ulcer received either intravenous infusion
      of famotidine (40 mg/day) (n = 207, 163 males, 44 females, mean age 61.5 years)
      or drip infusion of omeprazole (40 mg/day; n = 193, 134 males, 59 females, mean
      age 59.8 years) after successful endoscopic treatment. The fasting duration,
      hospital stay, volume of transfused blood, incidence of rebleeding and mortality
      were compared between the two groups. RESULTS: The incidence of rebleeding did
      not differ significantly between the famotidine group (9%) and the omeprazole
      group (8%). The mean hospital stay was significantly shorter in the omeprazole
      group (18.4 days) than in the famotidine group (21.5 days, P = 0.009). However,
      there was no statistically significant difference in fasting duration, volume of
      transfused blood or mortality. CONCLUSION: Our findings indicate that intravenous
      infusion of famotidine after successful endoscopic treatment is equivalent to
      drip infusion of omeprazole for prevention of recurrent bleeding.

PMID- 15943852
TI  - Prevention of the rehaemorrhage of bleeding peptic ulcers: effects of
      Helicobacter pylori eradication and acid suppression.
AB  - AIM: This study aimed to investigate the consequences of Helicobacter pylori
      eradication and acid suppression on rehaemorrhage caused by bleeding peptic
      ulcers. METHODS: A total of 320 patients who had been diagnosed with bleeding
      peptic ulcers between January 1994 and December 2001 were included in the study.
      Cases between 1994 and 1997, prior to the introduction of eradication therapy,
      were assigned to group A, whereas those between 1998 and 2001, after the
      eradication therapy, were assigned to group B. RESULTS: Of the 320 cases, 162
      were designated as group A (113 gastric ulcers and 49 duodenal ulcers) and 158 as
      group B (116 and 42, respectively). Rehaemorrhage occurred in 24 cases (15%) and
      five cases (3%) in groups A and B, respectively, presenting a significantly
      decreased rate of rehaemorrhage in group B. Among those without eradication,
      rehaemorrhage was observed in 15 of 128 cases (12%) that received treatment with
      histamine(2)-receptor antagonist (famotidine), and 14 of 142 cases (10%) treated
      with proton-pump inhibitors, with no significant difference between the two.
      CONCLUSIONS: Helicobacter pylori eradication lowered the rates of rehaemorrhage.
      Treatment with histamine(2)-receptor antagonist or proton-pump inhibitors did not
      produce a difference in the rate of rehaemorrhage.

PMID- 15943853
TI  - Mucosal proinflammatory cytokine and chemokine expression of gastroduodenal
      lesions in Crohn's disease.
AB  - BACKGROUND: The stomach and the duodenum are frequent sites of involvement by
      diminutive lesions in Crohn's disease (CD). AIM: To assess mucosal
      proinflammatory cytokines and chemokines in gastroduodenal lesions of CD.
      METHODS: 13C-Urea breath test and upper endoscopy were performed in 29 CD
      patients and seven control subjects, and biopsy specimens were obtained from the
      gastric cardia and the duodenum. Histology and mucosal levels of IL-1beta, IL
      8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of
      gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion
      (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients,
      these procedures were repeatedly performed after administration of famotidine.
      RESULTS: H. pylori was less frequently positive in CD patients than in controls
      (10% vs. 71%, P = 0.003). Prevalence of cardial and duodenal lesion was
      significantly higher in CD than in controls (59% vs. 0%, P = 0.008 for gastric
      lesion; 45% vs. 0%, P = 0.034 for duodenal lesion). There were no differences in
      IL-1beta, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1beta and
      IL-8 were significantly higher in positive duodenal lesion than in negative
      duodenal lesion. However, there were no such differences with respect to cardial
      lesions. Endoscopic findings remained unchanged after administration of
      famotidine, while there was a trend towards decreases in IL-1beta and IL-8 in the
      gastric cardia. CONCLUSIONS: The pathogenesis of diminutive lesions of CD may be
      different between the stomach and the duodenum. Famotidine may not have a
      therapeutic effect on duodenal lesion in CD.

PMID- 15943854
TI  - Histamine-2 receptor expression in gastric mucosa before and after Helicobacter
      pylori cure.
AB  - BACKGROUND: Helicobacter pylori infection prevents the occurrence of the
      tolerance phenomenon of Histamine-2 (H2) receptor antagonists. Gastro-esophageal
      reflux disease develops in some cases with the restoration of acid secretion
      after H. pylori eradication therapy. AIM: To clarify the mechanisms of H2
      receptor restoration after the eradication of H. pylori on parietal cells.
      METHODS: We enrolled 80 consecutive asymptomatic male patients with H. pylori
      infection, having chronic gastritis with or without the presence of peptic
      ulcers. Biopsy specimens from the greater curvatures at the mid-corpus of the
      stomach were obtained endoscopically from all subjects before and 12 weeks after
      the eradication of H. pylori. Degrees of gastric atrophy were evaluated by serum
      pepsinogen levels. The amounts of mRNA expression of H2 receptor were evaluated
      in each subject's gastric mucosa by real time reverse transcriptase-polymerase
      chain reaction (RT-PCR). RESULTS: H2 receptor mRNA expression levels
      significantly correlated with serum pepsinogens I and II ratios. The expression
      level of H2 receptor mRNA was lower in subjects with hypergastrinemia. The median
      expression level of H2 receptor after H. pylori eradication was threefold greater
      than prior to treatment. In addition, its restoration became more pronounced in
      subjects with severe gastric atrophy. However, a comparatively low restoration of
      H2 receptor mRNA was found in subjects with hypergastrinemia. CONCLUSIONS: H2
      receptor mRNA levels decrease with the progression of gastric atrophy induced by
      H. pylori infection, and are restored after H. pylori eradication. Such
      expression levels of H2 receptor may explain a part of the tolerance phenomenon
      to H2 receptor antagonists.

PMID- 15943855
TI  - Effect of long-term half-dose famotidine therapy on corpus gastritis in peptic
      ulcer disease.
AB  - BACKGROUND: Recent studies showed that acid-suppressive therapy aggravates corpus
      gastritis in patients with Helicobacter pylori infection. AIM: The aim of this
      study was to evaluate the effect of famotidine, a histamine receptor antagonist
      on corpus gastritis in patients with peptic ulcer disease. METHODS: We enrolled
      287 patients, 173 with duodenal ulcer and 114 with gastric ulcer and 100 patients
      with H. pylori-positive gastritis as control subjects. Patients with peptic ulcer
      were classified according to whether or not they received famotidine-maintenance
      therapy (20 mg/day) after primary treatment. At the time of endoscopy, biopsy
      specimens were obtained from the antrum and the corpus. The degrees of neutrophil
      and lymphocyte infiltration, atrophy and intestinal metaplasia were scored
      according to the updated Sydney System. RESULTS: The degrees of neutrophil
      infiltration and atrophy in the corpus were significantly less in patients with
      gastric ulcer or duodenal ulcer than in patients with H. pylori-positive
      gastritis (P < 0.01). Differences in the degrees of neutrophil infiltration and
      atrophy in the corpus between the non-maintenance group and the maintenance group
      were not significant. CONCLUSION: Long-term therapy with famotidine does not
      appear to lead to an increase in the incidence of corpus gastritis or corpus
      atrophy in patients with peptic ulcer disease.

PMID- 15943856
TI  - Comparison of hemostatic effects by route of H2 receptor antagonist
      administration following endoscopic mucosal resection in patients with neoplastic
      gastric lesions.
AB  - BACKGROUND: To date, there has not been an in-depth investigation to identify
      differences in the effects of bleeding prevention among different routes of
      administration of H2 receptor antagonists to treat gastric ulcers following
      endoscopic mucosal resection (EMR). AIM: To prospectively compare the frequency
      of bleeding following EMR between patients treated with intravenous (IV)
      famotidine and those with oral famotidine. METHODS: Fifty-three patients with
      neoplastic gastric lesions (33 carcinoma and 20 adenoma) treated by EMR were
      included. Subjects underwent EMR with circumferential mucosal incision assisted
      by submucosal injection of sodium hyaluronate (EMRSH), followed by IV or oral
      (PO) administration of famotidine at a dosage of 40 mg/day for 2 days. Patients
      with odd ID numbers were assigned to IV therapy (30 cases) while even numbers
      were given PO therapy (23 cases). Frequencies and endoscopic findings of bleeding
      during the first 2 days after EMR were examined. RESULTS: Frequency of bleeding
      within 2 days after EMR was 3 and 4% in IV and PO patients, respectively, showing
      no significant difference. No significant difference was seen in the endoscopic
      findings of bleeding and therapy, either, with respective IV and PO findings at
      23 and 26%. CONCLUSIONS: No significant difference was observed in frequency of
      bleeding within 2 days after gastric EMR between IV and oral administrations of
      famotidine.

PMID- 15943857
TI  - A prospective randomized trial of either famotidine or omeprazole for the
      prevention of bleeding after endoscopic mucosal resection and the healing of
      endoscopic mucosal resection-induced ulceration.
AB  - BACKGROUND: It has been reported that inhibitors of gastric acid secretion
      prevent bleeding after endoscopic mucosal resection for mucosal gastric neoplasm.
      However, uncertain whether an histamine2-receptor antagonist or proton-pump
      inhibitor is more effective. AIM: To evaluate prospectively the effectiveness of
      famotidine or omeprazole for ulcer management after endoscopic mucosal resection.
      METHODS: From July 2003 to October 2004, 57 patients were randomly assigned to
      famotidine or omeprazole for the management of endoscopic mucosal resection. Both
      drugs were given intravenously for the first 2 days, thereafter by mouth. The
      bleeding rates after endoscopic mucosal resection, the effects on the healing of
      endoscopic mucosal resection-induced ulceration, and cost-benefits were compared.
      RESULTS: Twenty-eight patients received famotidine and 29 received omeprazole. No
      significant difference was observed between the two groups in patient
      characteristics. The bleeding rates after endoscopic mucosal resection were not
      significantly different (18% vs. 14%) between the groups. Similarly, no
      differences were seen in the size of the endoscopic mucosal resection-induced
      ulceration at 1, 30 and 60 days after resection between groups. The total costs
      of anti-secretory agents demonstrated a significant cost-benefit to those treated
      with famotidine (10,420 yen vs. 17,782 yen). CONCLUSIONS: Famotidine is suggested
      as a better alternative to omeprazole for the management of endoscopic mucosal
      resection, as it showed a clear cost-benefit, and the healing results after
      endoscopic mucosal resection were similar for the two treatment strategies.

PMID- 15943858
TI  - Preoperative diagnosis of a mediastinal granular cell tumor by EUS-FNA: a case
      report and review of the literature.
AB  - We report the first case of a posterior mediastinal granular cell tumor initially
      diagnosed on cytologic material obtained via endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA) in a 51-year-old male with a prior history of colon
      cancer. Aspirates obtained were cellular and composed of polygonal cells with
      abundant granular cytoplasm and small, round dark nuclei. An immunoperoxidase
      stain performed on the cell block for antibodies to S-100 protein showed strong,
      diffuse staining of the cytoplasmic granules. Electron microscopy performed on
      the cell block revealed numerous cytoplasmic lysosomes. This is the first case
      report in the English literature of a definitive preoperative diagnosis of a
      mediastinal granular cell tumor utilizing material obtained via EUS-FNA.

PMID- 15943859
TI  - Unhappy doctors? A longitudinal study of life and job satisfaction among
      Norwegian doctors 1994-2002.
AB  - BACKGROUND: General opinion is that doctors are increasingly dissatisfied with
      their job, but few longitudinal studies exist. This study has been conducted to
      investigate a possible decline in professional and personal satisfaction among
      doctors by the turn of the century. METHODS: We have done a survey among a
      representative sample of 1,174 Norwegian doctors in 2002 (response rate 73 %) and
      compared the findings with answers to the same questions by (most of) the same
      doctors in 1994 and 2000. The main outcome measures were self reported levels of
      life satisfaction and job satisfaction according to the Job Satisfaction Scale
      (JSS). RESULTS: Most Norwegian doctors are happy. They reported an average life
      satisfaction of 5.21 in 1994 and 5.32 in 2002 on a scale from 1 (extremely
      dissatisfied) to 7 (extremely satisfied). Half of the respondents reported a very
      high level of general life satisfaction (a score of 6 or 7) while only one third
      said they would have reported this high level of satisfaction five years ago. The
      doctors thought that they had a higher level of job satisfaction than other
      comparable professional groups. The job satisfaction scale among the same doctors
      showed a significant increase from 1994 to 2002. Anaesthesiologists and
      internists reported a lower and psychiatrists and primary care doctors reported a
      higher level of job satisfaction than the average. CONCLUSION: Norwegian doctors
      seem to have enjoyed an increasing level of life and job satisfaction rather than
      a decline over the last decade. This challenges the general impression of unhappy
      doctors as a general and worldwide phenomenon.

PMID- 15943860
TI  - Gonadal steroids differentially modulate neurotoxicity of HIV and cocaine:
      testosterone and ICI 182,780 sensitive mechanism.
AB  - BACKGROUND: HIV Associated Dementia (HAD) is a common complication of human
      immunodeficiency virus (HIV) infection that erodes the quality of life for
      patients and burdens health care providers. Intravenous drug use is a major route
      of HIV transmission, and drug use is associated with increased HAD. Specific
      proteins released as a consequence of HIV infection (e.g., gp120, the HIV
      envelope protein and Tat, the nuclear transactivating protein) have been
      implicated in the pathogenesis of HAD. In primary cultures of human fetal brain
      tissue, subtoxic doses of gp120 and Tat are capable of interacting with a
      physiologically relevant dose of cocaine, to produce a significant synergistic
      neurotoxicity. Using this model system, the neuroprotective potential of gonadal
      steroids was investigated. RESULTS: 17beta-Estradiol (17beta-E2), but not 17alpha
      estradiol (17alpha-E2), was protective against this combined neurotoxicity.
      Progesterone (PROG) afforded limited neuroprotection, as did dihydrotestosterone
      (DHT). The efficacy of 5alpha-testosterone (T)-mediated neuroprotection was
      robust, similar to that provided by 17beta-E2. In the presence of the specific
      estrogen receptor (ER) antagonist, ICI-182,780, T's neuroprotection was
      completely blocked. Thus, T acts through the ER to provide neuroprotection
      against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated
      concentration-dependent neuroprotection, possibly attributable to cholesterol's
      serving as a steroid hormone precursor in neurons. CONCLUSION: Collectively, the
      present data indicate that cocaine has a robust interaction with the HIV proteins
      gp120 and Tat that produces severe neurotoxicity, and this toxicity can be
      blocked through pretreatment with ER agonists.

PMID- 15943862
TI  - Estimated physical activity in Bavaria, Germany, and its implications for obesity
      risk: results from the BVS-II Study.
AB  - BACKGROUND: Adequate physical activity (PA) is considered as a key factor in the
      fight against the obesity epidemic. Therefore, detailed description of the actual
      PA and its components in the population is necessary. Additionally, this study
      aims to investigate the association between PA and obesity risk in a
      representative population sample in Bavaria, Germany. METHODS: Data from 893
      participants (age 13-80 years) of the Bavarian Food Consumption Survey II (BVS
      II) were used. In each participant, three computer-based 24-hour recalls were
      conducted by telephone assessing type and duration of PA in the domains
      occupation, sports, other strenuous leisure time activities (of mostly moderate
      intensity) as well as TV/PC use in leisure time and duration of sleeping. After
      assigning metabolic equivalents (METs) to each activity, estimates of energy
      expenditure (MET*h) and total daily PA level (PALest.) were calculated. In a
      subgroup of adults (n = 568) with anthropometric measurements logistic regression
      models were used to quantify the impact of PA on obesity risk. RESULTS: Estimated
      average PA in women and men was 38.5 +/- 5.0 and 40.6 +/- 9.3 MET*h/d,
      respectively, corresponding to PALest. values of 1.66 +/- 0.22 and 1.75 +/- 0.40.
      Obese subjects showed lower energy expenditure in the categories sports,
      occupation, and sleeping, while the time spent with TV/PC during leisure time was
      highest. This is confirmed in logistic regression analyses revealing a
      statistically significant association between obesity and TV/PC use during
      leisure time, while sports activity was inversely related to obesity risk.
      Overall, less than 1/3 of the study participants reached the recommended PAL of
      >or= 1.75. Subjects within the recommended range of PA had an about 60 % (odds
      ratio = 0.43; 95% CI: 0.21-0.85) reduced risk of obesity as compared to inactive
      subjects with a PALest. <1.5. CONCLUSION: Based on the results of short-term PA
      patterns, a major part of the Bavarian adult population does not reach the
      recommendations (PAL>1.75; moderate PA of > 30 min/d). Despite the limitations of
      the study design, the existing associations between sports activity, TV/PC use
      and obesity risk in this population give further support to the recommendation of
      increasing sports activity and reducing sedentary behaviour in order to prevent
      rising rates of obesity.

PMID- 15943863
TI  - An information value based analysis of physical and climatic factors affecting
      dengue fever and dengue haemorrhagic fever incidence.
AB  - BACKGROUND: Vector-borne diseases are the most dreaded worldwide health problems.
      Although many campaigns against it have been conducted, Dengue Fever (DF) and
      Dengue Haemorrhagic Fever (DHF) are still the major health problems of Thailand.
      The reported number of dengue incidences in 1998 for the Thailand was 129,954, of
      which Sukhothai province alone reported alarming number of 682. It was the second
      largest epidemic outbreak of dengue after 1987. Government arranges the remedial
      facilities as and when dengue is reported. But, the best way to control is to
      prevent it from happening. This will be possible only when knowledge about the
      relationship of DF/DHF with climatic and physio-environmental agents is
      discovered. This paper explores empirical relationship of climatic factors
      rainfall, temperature and humidity with the DF/DHF incidences using multivariate
      regression analysis. Also, a GIS based methodology is proposed in this paper to
      explore the influence of physio-environmental factors on dengue incidences.
      Remotely sensed data provided important data about physical environment and have
      been used for many vector borne diseases. Information Values (IV) method was
      utilised to derive influence of various factors in the quantitative terms.
      Researchers have not applied this type of analysis for dengue earlier. Sukhothai
      province was selected for the case study as it had high number of dengue cases in
      1998 and also due to its diverse physical setting with variety of land use/land
      cover types. RESULTS: Preliminary results demonstrated that physical factors
      derived from remotely sensed data could indicate variation in physical risk
      factors affecting DF/DHF. A composite analysis of these three factors with dengue
      incidences was carried out using multivariate regression analysis. Three
      empirical models ER-1, ER-2 and ER-3 were evaluated. It was found that these
      three factors have significant relation with DF/DHF incidences and can be related
      to the forecast expected number of dengue cases. The results have shown
      significantly high coefficient of determination if applied only for the rainy
      season using empirical relation-2 (ER-2). These results have shown further
      improvement once a concept of time lag of one month was applied using the ER-3
      empirical relation. ER-3 model is most suitable for the Sukhothai province in
      predicting possible dengue incidence with 0.81 coefficient of determination. The
      spatial statistical relationship of various land use/land cover classes with
      dengue-affected areas was quantified in the form of information value received
      from GIS analysis. The highest information value was obtained for the Built-up
      area. This indicated that Built-up area has the maximum influence on the
      incidence of dengue. The other classes showing negative values indicate lesser
      influence on dengue epidemics. Agricultural areas have yielded moderate risk
      areas based on their medium high information values. Water bodies have shown
      significant information value for DF/DHF only in one district. Interestingly,
      forest had shown no influence on DF/DHF. CONCLUSION: This paper explores the
      potential of remotely sensed data and GIS technology to analyze the spatial
      factors affecting DF/DHF epidemic. Three empirical models were evaluated. It was
      found that Empirical Relatrion-3 (ER-3) has yielded very high coefficient of
      determination to forecast the number of DF/DHF incidence. An analysis of physio
      environmental factors such as land use/land cover types with dengue incidence was
      carried out. Influence of these factors was obtained in quantitative terms using
      Information Value method in the GIS environment. It was found that built-up areas
      have highest influence and constitute the highest risk zones. Forest areas have
      no influence on DF/DHF epidemic. Agricultural areas have moderate risk in DF/DHF
      incidences. Finally the dengue risk map of the Sukhothai province was developed
      using Information Value method. Dengue risk map can be used by the Public Health
      Department as a base map for applying preventive measures to control the dengue
      outbreak. Public Health Department can initiate their effort once the ER-3
      predicts a possibility of significant high dengue incidence. This will help in
      focussing the preventive measures being applied on priority in very high and high
      risk zones and help in saving time and money.

PMID- 15943861
TI  - How does study quality affect the results of a diagnostic meta-analysis?
AB  - BACKGROUND: The use of systematic literature review to inform evidence based
      practice in diagnostics is rapidly expanding. Although the primary diagnostic
      literature is extensive, studies are often of low methodological quality or
      poorly reported. There has been no rigorously evaluated, evidence based tool to
      assess the methodological quality of diagnostic studies. The primary objective of
      this study was to determine the extent to which variations in the quality of
      primary studies impact the results of a diagnostic meta-analysis and whether this
      differs with diagnostic test type. A secondary objective was to contribute to the
      evaluation of QUADAS, an evidence-based tool for the assessment of quality in
      diagnostic accuracy studies. METHODS: This study was conducted as part of large
      systematic review of tests used in the diagnosis and further investigation of
      urinary tract infection (UTI) in children. All studies included in this review
      were assessed using QUADAS, an evidence-based tool for the assessment of quality
      in systematic reviews of diagnostic accuracy studies. The impact of individual
      components of QUADAS on a summary measure of diagnostic accuracy was investigated
      using regression analysis. The review divided the diagnosis and further
      investigation of UTI into the following three clinical stages: diagnosis of UTI,
      localisation of infection, and further investigation of the UTI. Each stage used
      different types of diagnostic test, which were considered to involve different
      quality concerns. RESULTS: Many of the studies included in our review were poorly
      reported. The proportion of QUADAS items fulfilled was similar for studies in
      different sections of the review. However, as might be expected, the individual
      items fulfilled differed between the three clinical stages. Regression analysis
      found that different items showed a strong association with test performance for
      the different tests evaluated. These differences were observed both within and
      between the three clinical stages assessed by the review. The results of
      regression analyses were also affected by whether or not a weighting (by sample
      size) was applied. Our analysis was severely limited by the completeness of
      reporting and the differences between the index tests evaluated and the reference
      standards used to confirm diagnoses in the primary studies. Few tests were
      evaluated by sufficient studies to allow meaningful use of meta-analytic pooling
      and investigation of heterogeneity. This meant that further analysis to
      investigate heterogeneity could only be undertaken using a subset of studies, and
      that the findings are open to various interpretations. CONCLUSION: Further work
      is needed to investigate the influence of methodological quality on the results
      of diagnostic meta-analyses. Large data sets of well-reported primary studies are
      needed to address this question. Without significant improvements in the
      completeness of reporting of primary studies, progress in this area will be
      limited.

PMID- 15943865
TI  - A space-time analysis of the proportion of late stage breast cancer in
      Massachusetts, 1988 to 1997.
AB  - BACKGROUND: Early detection is the best way to control breast cancer. This
      observational epidemiologic study uses ten years of data, 1988-1997, to determine
      whether the observed variations in the proportion of breast cancers diagnosed at
      late stage are simply random or are statistically significant with respect to
      both geographical location and time. RESULTS: A total of three spatial-temporal
      areas were found to deviate significantly from randomness in the unadjusted
      analysis; one of the three areas contained statistically significant excesses in
      proportion of late stage, while two areas were identified as significantly lower
      than expected. The area of excess spanned the first three years of the study
      period, while the low areas spanned the last five years of the study period. Some
      of these areas were no longer statistically significant when adjustments were
      made for SES and urban/rural status. CONCLUSION: Although there was an area of
      excess in eastern Massachusetts, it only spanned the first three years of the
      study period. The low areas were fairly consistent, spanning the last five years
      of the study period.

PMID- 15943864
TI  - Prediction and verification of microRNA targets by MovingTargets, a highly
      adaptable prediction method.
AB  - BACKGROUND: MicroRNAs (miRNAs) mediate a form of translational regulation in
      animals. Hundreds of animal miRNAs have been identified, but only a few of their
      targets are known. Prediction of miRNA targets for translational regulation is
      challenging, since the interaction with the target mRNA usually occurs via
      incomplete and interrupted base pairing. Moreover, the rules that govern such
      interactions are incompletely defined. RESULTS: MovingTargets is a software
      program that allows a researcher to predict a set of miRNA targets that satisfy
      an adjustable set of biological constraints. We used MovingTargets to identify a
      high-likelihood set of 83 miRNA targets in Drosophila, all of which adhere to
      strict biological constraints. We tested and verified 3 of these predictions in
      cultured cells, including a target for the Drosophila let-7 homolog. In addition,
      we utilized the flexibility of MovingTargets by relaxing the biological
      constraints to identify and validate miRNAs targeting tramtrack, a gene also
      known to be subject to translational control dependent on the RNA binding protein
      Musashi. CONCLUSION: MovingTargets is a flexible tool for the accurate prediction
      of miRNA targets in Drosophila. MovingTargets can be used to conduct a genome
      wide search of miRNA targets using all Drosophila miRNAs and potential targets,
      or it can be used to conduct a focused search for miRNAs targeting a specific
      gene. In addition, the values for a set of biological constraints used to define
      a miRNA target are adjustable, allowing the software to incorporate the rules
      used to characterize a miRNA target as these rules are experimentally determined
      and interpreted.

PMID- 15943866
TI  - The use of non-bronchoscopic brushings to study the paediatric airway.
AB  - BACKGROUND: The use of cytology brushes for the purpose of obtaining respiratory
      cells from adults for clinical and research purposes is well established.
      However, the safety and utility of non-bronchoscopic brushings to study the
      paediatric airway has not been assessed. The purpose of this study was to assess
      the practicality of using non-bronchoscopic brushing to sample epithelial cells
      from children for investigation of epithelial function in health and disease
      using a wide range of molecular and cellular techniques. METHODS: Non
      bronchoscopic brushing was investigated in a non-selected cohort of healthy, and
      mildly asthmatic children presenting for surgery unrelated to respiratory
      conditions, at the major children's hospital in Perth. Safety and side-effects of
      the procedure were assessed. Cell number, phenotype and viability were measured
      for all samples. The potential of these cells for use in long-term cell culture,
      immunohistochemistry, western blotting, quantitative PCR and gene arraying was
      examined. RESULTS: Non-bronchoscopic brushing was well tolerated in all children.
      The only significant side effect following the procedure was cough: nursing staff
      reported cough in 20% of patients; parents reported cough in 40% of patients.
      Cells sampled were of sufficient quantity and quality to allow cell culture in
      93% of samples. Similarly, protein and RNA extracted from the cells was suitable
      for investigation of both gene and protein expression using micro-array and real
      time PCR. CONCLUSION: Non-bronchoscopic brushing in children is safe and easy to
      perform, and is not associated with any complications. Using this technique,
      adequate numbers of epithelial cells can be retrieved to allow cell culture,
      western blotting, real time PCR, and microarray analysis. The purpose of this
      study is to demonstrate the utility of non-bronchoscopic airway brushing to
      obtain and study epithelial cells and to encourage others so that we can
      accelerate our knowledge regarding the role of the epithelium in childhood
      respiratory disease.

PMID- 15943867
TI  - Respiratory rehabilitation after acute exacerbation of COPD may reduce risk for
      readmission and mortality -- a systematic review.
AB  - BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (COPD)
      represent a major burden for patients and health care systems. Respiratory
      rehabilitation may improve prognosis in these patients by addressing relevant
      risk factors for exacerbations such as low exercise capacity. To study whether
      respiratory rehabilitation after acute exacerbation improves prognosis and health
      status compared to usual care, we quantified its effects using meta-analyses.
      METHODS: Systematic review of randomized controlled trials identified by searches
      in six electronic databases, contacts with experts, hand-searches of
      bibliographies of included studies and conference proceedings. We included
      randomized trials comparing the effect of respiratory rehabilitation and usual
      care on hospital admissions, health-related quality of life (HRQL), exercise
      capacity and mortality in COPD patients after acute exacerbation. Two reviewers
      independently selected relevant studies, extracted the data and evaluated the
      study quality. We pooled the results using fixed effects models where
      statistically significant heterogeneity (p < or = 0.1) was absent. RESULTS: We
      identified six trials including 230 patients. Respiratory rehabilitation reduced
      the risk for hospital admissions (pooled relative risk 0.26 [0.12-0.54]) and
      mortality (0.45 [0.22-0.91]). Weighted mean differences on the Chronic
      Respiratory Questionnaire were 1.37 (95% CI 1.13-1.61) for the fatigue domain,
      1.36 (0.94-1.77) for emotional function and 1.88 (1.67-2.09) for mastery.
      Weighted mean differences for the St. Georges Respiratory Questionnaire total
      score, impacts and activities domains were -11.1 (95% CI -17.1 to -5.2), -17.1
      (95% CI -23.6 to -10.7) and -9.9 (95% CI -18.0 to -1.7). In all trials,
      rehabilitation improved exercise capacity (64-215 meters in six-minute walk tests
      and weighted mean difference for shuttle walk test 81 meter, 95% CI 48-115).
      CONCLUSION: Evidence from six trials suggests that respiratory rehabilitation is
      effective in COPD patients after acute exacerbation. Larger trials, however, are
      needed to further investigate the role of respiratory rehabilitation after acute
      exacerbation and its potential to reduce costs caused by COPD.

PMID- 15943868
TI  - Changes in social inequality with respect to health-related living conditions of
      6-year-old children in East Germany after re-unification.
AB  - BACKGROUND: Since Germany re-unified in 1990, substantial social and economic
      changes have happened in East Germany, the former socialist German Democratic
      Republic (GDR). The aim of this study was to investigate the influence of these
      socio-economic changes in East Germany on the association between social status,
      measured by parental educational level, and health-related living conditions of
      children during the ten-year period after re-unification. METHODS: In total,
      25,864 6-year-old school beginner children (51.2% male and 48.8% female)
      participated in cross-sectional studies which have been repeated every year from
      1991 to 2000 in East Germany. Parental educational level as a social indicator
      was the independent variable. Dependent variables included not employed parents,
      small living space and health-related living conditions (e. g. damp housing,
      single oven heating and living at busy road). The relationships were described by
      odds ratios using logistic regression. RESULTS: A large overall effect of
      parental educational level on health-related living conditions was observed. The
      time trends showed that the situation regarding small living space, damp housing
      conditions and single oven heating improved from 1991 to 2000, while regarding
      not employed parents (1996-2000) and living at busy road (1991-2000) did not, but
      even deteriorated. 6-year old children with low parental educational level, who
      lived at the time of re-unification, were often under damp housing conditions and
      with single oven heating at homes. Nevertheless, this social inequality has
      almost vanished ten years later. In contrast, we found an increasing gap between
      low and high parental educational level with respect to the proportion of parents
      who were not employed (22%: 4% gain), or lived under cramped housing conditions
      (22%: 37% reduction), or close to a busy road (7% gain: 2% reduction).
      CONCLUSION: The social inequalities which already existed under the socialist
      system in East Germany persisted in the system of social market economy between
      1991 and 2000. 6-year-old children from families with the lowest social status
      were living under the worst domestic conditions (e. g. living at busy road,
      having damp housing conditions, single oven heating and small living space) and
      for some conditions (e. g. living at busy road and having small living space) the
      gap betweenlow and high social status was even bigger in 2000 than in 1991.

PMID- 15943870
TI  - Geographic variations of childhood asthma hospitalization and outpatient visits
      and proximity to ambient pollution sources at a U.S.-Canada border crossing.
AB  - BACKGROUND: Childhood asthma is a significant public health problem in the United
      States and evidence is accumulating regarding the contribution from traffic and
      ambient air pollution. This study is a companion piece of a related Buffalo
      asthma study in adults recently published in the July 2004 issue of American
      Journal of Public Health. This study focuses on children under 18 years of age
      diagnosed with asthma during a three-year period (2000-2002). In order to
      determine the effects of particulate air pollution on public health, we conducted
      an ecologic study of childhood asthma and point-source respirable particulate air
      pollution in patients diagnosed with asthma (n = 6,425). Patients diagnosed with
      gastroenteritis (n = 5,132) were used as controls. RESULTS: Although the results
      of this study show spatial patterns similar to the ones observed in the adult
      study, a multiple-comparison test shows that EPA-designated focus sites located
      in Buffalo's east side are statistically (p < 0.008) more linked to childhood
      asthma than sites located elsewhere. CONCLUSION: Findings of this study can be
      useful in geographic targeting and in the design of optimal and preventive
      measures.

PMID- 15943869
TI  - Motives for choosing growth-enhancing hormone treatment in adolescents with
      idiopathic short stature: a questionnaire and structured interview study.
AB  - BACKGROUND: Growth-enhancing hormone treatment is considered a possible
      intervention in short but otherwise healthy adolescents. Although height gain is
      an obvious measure for evaluating hormone treatment, this may not be the ultimate
      goal for the person, but rather a means to reach other goals such as the
      amelioration of current height-related psychosocial problems or the enhancement
      of future prospects in life and society. The aim of our study was to clarify the
      motives of adolescents and their parents when choosing to participate in a growth
      enhancing trial combining growth hormone and puberty-delaying hormone treatment.
      METHODS: Participants were early pubertal adolescents (25 girls, 13 boys) aged
      from 11 to 13 years (mean age 11.5 years) with a height standard deviation score
      (SDS) ranging from -1.03 to -3.43. All had been classified as idiopathic short
      stature or persistent short stature born small for the gestational age
      (intrauterine growth retardation) on the basis of a height SDS below -2, or had a
      height SDS between -1 and -2 and a predicted adult height SDS below -2. The
      adolescents and their parents completed questionnaires and a structured interview
      on the presence of height-related stressors, parental worries about their child's
      behavior and future prospects, problems in psychosocial functioning, and
      treatment expectations. Questionnaire scores were compared to norms of the
      general Dutch population. RESULTS: The adolescents reported normal psychosocial
      functioning and highly positive expectations of the treatment in terms of height
      gain, whereas the parents reported that their children encountered some
      behavioral problems (being anxious/depressed, and social and attention problems)
      and height-related stressors (being teased and juvenilized). About 40% of the
      parents were worried about their children's future prospects for finding a spouse
      or job. The motives of the adolescents and their parents exhibited rather
      different profiles. The most prevalent parental worries related to the current or
      future functioning of their children, while a few cases were characterized by no
      observed motives or by psychosocial problems only reported by the adolescents
      themselves. CONCLUSION: The motives for participating in a growth-enhancing
      hormone trial are more obvious in the parents than in the adolescents themselves.
      Two out of three parents report worries about the future opportunities or observe
      modest current psychosocial problems in their children. The adolescents want to
      gain height, but the motivation underlying this remains unclear. Few of the
      adolescents experience psychosocial problems. Our analyses revealed differences
      among individuals in terms of motives, which implies that in an evaluation of
      hormone treatment, the importance of divergent outcome variables will also differ
      among individuals. Effectiveness evaluations of hormone treatment to increase
      height and the consequential fulfillment of other goals must be awaited.

PMID- 15943871
TI  - Determinants of persistence in hypertensive patients treated with irbesartan:
      results of a postmarketing survey.
AB  - BACKGROUND: Persistence is a key factor for long-term blood pressure control,
      which is of high prognostic importance for patients at increased cardiovascular
      risk. Here we present the results of a post-marketing survey including 4769
      hypertensive patients treated with irbesartan in 886 general practices in
      Switzerland. The goal of this survey was to evaluate the tolerance and the blood
      pressure lowering effect of irbesartan as well as the factors affecting
      persistence in a large unselected population. METHODS: Prospective observational
      survey conducted in general practices in all regions of Switzerland. Previously
      untreated and uncontrolled pre-treated patients were started with a daily dose of
      150 mg irbesartan and followed up to 6 months. RESULTS: After an observation time
      slightly exceeding 4 months, the average reduction in systolic and diastolic
      blood pressure was 20 (95% confidence interval (CI) -19.6 to -20.7 mmHg) and 12
      mmHg (95% CI -11.4 to -12.1 mmHg), respectively. At this time, 26% of patients
      had a blood pressure < 140/90 mmHg and 60% had a diastolic blood pressure < 90
      mmHg. The drug was well tolerated with an incidence of adverse events (dizziness,
      headaches,...) of 8.0%. In this survey more than 80% of patients were still on
      irbesartan at 4 month. The most important factors predictive of persistence were
      the tolerability profile and the ability to achieve a blood pressure target < or
      = 140/90 mmHg before visit 2. Patients who switched from a fixed combination
      treatment tended to discontinue irbesartan more often whereas those who abandoned
      the previous treatment because of cough (a class side effect of ACE-Inhibitors)
      were more persistent with irbesartan. CONCLUSION: The results of this survey
      confirm that irbesartan is effective, well tolerated and well accepted by
      patients, as indicated by the good persistence. This post-marketing survey also
      emphasizes the importance of the tolerability profile and of achieving an early
      control of blood pressure as positive predictors of persistence.

PMID- 15943872
TI  - Association between reduced bronchodilatory effect of deep inspiration and loss
      of alveolar attachments.
AB  - BACKGROUND: We have previously shown that the bronchodilatory effect of deep
      inspiration is attenuated in individuals with COPD. This study was designed to
      investigate whether the impairment in this effect is associated with loss of
      alveolar attachments. METHODS: We measured deep inspiration (DI)-induced
      bronchodilation in 15 individuals with and without COPD (67 +/- 2.2 yrs of age,
      mean +/- SEM) undergoing lobar resection for peripheral pulmonary nodule. Prior
      to surgery, we measured TLCO and determined the bronchodilatory effect of deep
      inspiration after constricting the airways with methacholine. The number of
      destroyed alveolar attachments, as well as airway wall area and airway smooth
      muscle area, were determined in tumor-free, peripheral lung tissue. RESULTS: The
      bronchodilatory effect of deep inspiration correlated inversely with the %
      destroyed attachments (r = -0.51, p = 0.05) and directly with the airway smooth
      muscle area (r = 0.59, p = 0.03), but not with the total wall area (r = 0.39, p =
      0.15). CONCLUSION: We postulate that attenuation of airway stretch due to loss of
      alveolar attachments contributes to the loss of the bronchodilatory effect of
      lung inflation in COPD.

PMID- 15943873
TI  - Agreement between diagnoses reached by clinical examination and available
      reference standards: a prospective study of 216 patients with lumbopelvic pain.
AB  - BACKGROUND: The tissue origin of low back pain (LBP) or referred lower extremity
      symptoms (LES) may be identified in about 70% of cases using advanced imaging,
      discography and facet or sacroiliac joint blocks. These techniques are invasive
      and availability varies. A clinical examination is non-invasive and widely
      available but its validity is questioned. Diagnostic studies usually examine
      single tests in relation to single reference standards, yet in clinical practice,
      clinicians use multiple tests and select from a range of possible diagnoses.
      There is a need for studies that evaluate the diagnostic performance of clinical
      diagnoses against available reference standards. METHODS: We compared blinded
      clinical diagnoses with diagnoses based on available reference standards for
      known causes of LBP or LES such as discography, facet, sacroiliac or hip joint
      blocks, epidurals injections, advanced imaging studies or any combination of
      these tests. A prospective, blinded validity design was employed.
      Physiotherapists examined consecutive patients with chronic lumbopelvic pain
      and/or referred LES scheduled to receive the reference standard examinations.
      When diagnoses were in complete agreement regardless of complexity, "exact"
      agreement was recorded. When the clinical diagnosis was included within the
      reference standard diagnoses, "clinical agreement" was recorded. The proportional
      chance criterion (PCC) statistic was used to estimate agreement on multiple
      diagnostic possibilities because it accounts for the prevalence of individual
      categories in the sample. The kappa statistic was used to estimate agreement on
      six pathoanatomic diagnoses. RESULTS: In a sample of chronic LBP patients (n =
      216) with high levels of disability and distress, 67% received a patho-anatomic
      diagnosis based on available reference standards, and 10% had more than one
      tissue origin of pain identified. For 27 diagnostic categories and combinations,
      chance clinical agreement (PCC) was estimated at 13%. "Exact" agreement between
      clinical and reference standard diagnoses was 32% and "clinical agreement" 51%.
      For six pathoanatomic categories (disc, facet joint, sacroiliac joint, hip joint,
      nerve root and spinal stenosis), PCC was 33% with actual agreement 56%. There was
      no overlap of 95% confidence intervals on any comparison. Diagnostic agreement on
      the six most common patho-anatomic categories produced a kappa of 0.31.
      CONCLUSION: Clinical diagnoses agree with reference standards diagnoses more
      often than chance. Using available reference standards, most patients can have a
      tissue source of pain identified.

PMID- 15943874
TI  - Type I Gaucher disease with exophthalmos and pulmonary arteriovenous
      malformation.
AB  - BACKGROUND: Gaucher disease type I, the non-neuropathic type, usually presents in
      adulthood with hepatosplenomegaly. We report here an adult with type I Gaucher
      disease presented with unusual and severe clinical manifestations. CASE
      PRESENTATION: Hepatosplenomegaly, bone crisis and fractures occurred at early
      childhood, and splenectomy was performed at the age of 5. Exophthalmos with
      increase in retrobulbar space was noted when the patient was 30. Cerezyme
      infusion started at the age of 32; but unfortunately, pulmonary arteriovenous
      malformation with dyspnea and hypoxemia was found two years later. Gene analysis
      revealed V375L/L444P mutations in the beta-glucocerebrosidase gene. CONCLUSION:
      Although both eye and lung diseases have been associated with Gaucher disease,
      this is the first reported demonstration of exophthalmos and pulmonary
      arteriovenous malformation in the same patient. This case may therefore present
      an extremely severe and unusual form of type I Gaucher disease.

PMID- 15943875
TI  - Linkage mapping bovine EST-based SNP.
AB  - BACKGROUND: Existing linkage maps of the bovine genome primarily contain
      anonymous microsatellite markers. These maps have proved valuable for mapping
      quantitative trait loci (QTL) to broad regions of the genome, but more closely
      spaced markers are needed to fine-map QTL, and markers associated with genes and
      annotated sequence are needed to identify genes and sequence variation that may
      explain QTL. RESULTS: Bovine expressed sequence tag (EST) and bacterial
      artificial chromosome (BAC)sequence data were used to develop 918 single
      nucleotide polymorphism (SNP) markers to map genes on the bovine linkage map. DNA
      of sires from the MARC reference population was used to detect SNPs, and progeny
      and mates of heterozygous sires were genotyped. Chromosome assignments for 861
      SNPs were determined by twopoint analysis, and positions for 735 SNPs were
      established by multipoint analyses. Linkage maps of bovine autosomes with these
      SNPs represent 4585 markers in 2475 positions spanning 3058 cM. Markers include
      3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between
      marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean
      separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean
      (maximum) of 216 (366) informative meioses, and a mean 3-lod confidence interval
      of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean
      (maximum) of 55 (191) informative meioses, and were placed within a mean 8.5 cM 3
      lod confidence interval. Homologous human sequences were identified for 1159
      markers, including 582 newly developed and mapped SNP. CONCLUSION: Addition of
      these EST- and BAC-based SNPs to the bovine linkage map not only increases marker
      density, but provides connections to gene-rich physical maps, including annotated
      human sequence. The map provides a resource for fine-mapping quantitative trait
      loci and identification of positional candidate genes, and can be integrated with
      other data to guide and refine assembly of bovine genome sequence. Even after the
      bovine genome is completely sequenced, the map will continue to be a useful tool
      to link observable phenotypes and animal genotypes to underlying genes and
      molecular mechanisms influencing economically important beef and dairy traits.

PMID- 15943876
TI  - Medical students who decompress during the M-1 year outperform those who fail and
      repeat it: a study of M-1 students at the University of Illinois College of
      Medicine at Urbana-Champaign 1988-2000.
AB  - BACKGROUND: All medical schools must counsel poor-performing students, address
      their problems and assist them in developing into competent physicians. The
      objective of this study was to determine whether students with academic
      deficiencies in their M-1 year graduate more often, spend less time to complete
      the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by
      entering the Decompressed Program prior to failure of the M-1 year than those
      students who fail the M-1 year and then repeat it. METHOD: The authors reviewed
      the performance of M-1 students in the Decompressed Program and compared their
      outcomes to M-1 students who failed and fully repeated the M-1 year. To compare
      the groups upon admission, t-Tests comparing the Cognitive Index of students and
      MCAT scores from both groups were performed. Performance of the two groups after
      matriculation was also analyzed. RESULTS: Decompressed students were 2.1 times
      more likely to graduate. Decompressed students were 2.5 times more likely to pass
      USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of
      those in the decompressed group completed the program in five years compared to
      18% of the repeat group. CONCLUSION: Medical students who decompress their M-1
      year prior to M-1 year failure outperform those who fail their first year and
      then repeat it. These findings indicate the need for careful monitoring of M-1
      student performance and early intervention and counseling of struggling students.

PMID- 15943877
TI  - Comparison between swallowing and chewing of garlic on levels of serum lipids,
      cyclosporine, creatinine and lipid peroxidation in renal transplant recipients.
AB  - Hyperlipidemia and increased degree of oxidative stress are among the important
      risk factors for Atherosclerosis in renal transplant recipients (RTR). The
      Medical treatment of hyperlipidemia in RTR because of drugs side effects has been
      problematic, therefore alternative methods such as using of Garlic as an
      effective material in cholesterol lowering and inhibition of LDL Oxidation has
      been noted. For evaluation of garlic effect on RTR, 50 renal transplant patients
      with stable renal function were selected and divided into 2 groups. They took one
      clove of garlic (1 gr) by chewing or swallowing for two months, after one month
      wash-out period, they took garlic by the other route. Results indicated that
      although lipid profile, BUN, Cr, serum levels of cyclosporine and diastolic blood
      pressure did not change, Systolic blood pressure decreased from 138.2 to 132.8
      mmHg (p=0.001) and Malondialdehyde (MDA) decreased from 2.4 to 1.7 nmol/ml
      (p=0.009) by swallowing route, Cholesterol decreased from 205.1 to 195.3 mg/dl
      (p=0.03), triglyceride decreased from 195.7 to 174.8 mg/dl (p=0.008), MDA
      decreased from 2.5 to 1.6 nmol/ml (p=0.001), systolic blood pressure decreased
      from 137.5 to 129.8 mmHg (p=0.001), diastolic blood pressure decreased from 84.6
      to 77.6 mmHg (p=0.001) and Cr decreased from 1.51 to 1.44 mg/dl (p=0.03) by
      chewing route too. However HDL, LDL and cyclosporine serum levels had no
      significant differences by both of swallowing and chewing routes. We conclude
      that undamaged garlic (swallowed) had no lowering effect on lipid level of serum.
      But Crushed garlic (chewed) reduces cholesterol, triglyceride, MDA and blood
      pressure. Additionally creatinine reduced without notable decrease in
      cyclosporine serum levels may be due to cyclosporine nephrotoxicity ameliorating
      effect of garlic.

PMID- 15943878
TI  - Symptomatic relief precedes improvement of myocardial blood flow in patients
      under spinal cord stimulation.
AB  - BACKGROUND: Spinal cord electrical stimulation (SCS) has shown to be a treatment
      option for patients suffering from angina pectoris CCS III-IV although being on
      optimal medication and not suitable for conventional treatment strategies, e.g.
      CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under
      SCS therapy, there are only a few short-term studies that investigated
      alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct
      effect on myocardial perfusion. METHODS: A prospective study to investigate the
      short- and long-term effect of spinal cord stimulation (SCS) on myocardial
      ischemia in patients with refractory angina pectoris and coronary multivessel
      disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy
      3 months and 12 months after the beginning of neurostimulation. To further
      examine the relation between cardiac perfusion and functional status of the
      patients we measured exercise capacity (bicycle ergometry and 6-minute walk
      test), symptoms and quality of life (Seattle Angina Questionnaire [SAQ]), as
      well. RESULTS: 31 patients (65 +/- 11 SEM years; 25 male, 6 female) were included
      into the study. The average consumption of short acting nitrates (SAN) decreased
      rapidly from 12 +/- 1.6 times to 3 +/- 1 times per week. The walking distance and
      the maximum workload increased from 143 +/- 22 to 225 +/- 24 meters and 68 +/- 7
      to 96 +/- 12 watt after 3 months. Quality of life increased (SAQ) significantly
      after 3 month compared to baseline, as well. No further improvement was observed
      after one year of treatment. Despite the symptomatic relief and the improvement
      in maximal workload computer based analysis (Emory Cardiac Toolbox) of the MIBI
      SPECT studies after 3 months of treatment did not show significant alterations of
      myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6
      with decrease of ischemia, 2 patients dropped out during initial test phase).
      Interestingly, in the long-term follow up after one year 16 patients (of 27 who
      completed the one year follow up) showed a clear decrease of myocardial ischemia
      and only one patient still had an increase of ischemia compared to baseline.
      CONCLUSION: Thus, spinal cord stimulation not only relieves symptoms, but reduces
      myocardial ischemia as well. However, since improvement in symptoms and exercise
      capacity starts much earlier, decreased myocardial ischemia might not be a direct
      effect of neurostimulation but rather be due to a better coronary
      collateralisation because of an enhanced physical activity of the patients.

PMID- 15943879
TI  - The anti-tumor effect of Apo2L/TRAIL on patient pancreatic adenocarcinomas grown
      as xenografts in SCID mice.
AB  - BACKGROUND: Apo2L/TRAIL has considerable promise for cancer therapy based on the
      fact that this member of the tumor necrosis factor family induces apoptosis in
      the majority of malignant cells, while normal cells are more resistant.
      Furthermore, in many cells, when Apo2L/TRAIL is combined with chemotherapy, the
      effect is synergistic. The majority of this work has been carried out using cell
      lines. Therefore, investigation of how patient tumors respond to Apo2L/TRAIL can
      validate and/or complement information obtained from cell lines and prove
      valuable in the design of future clinical trials. METHODS: We have investigated
      the Apo2L/TRAIL sensitivity of patient derived pancreatic tumors using a patient
      tumor xenograft/ SCID mouse model. Mice bearing engrafted tumors were treated
      with Apo2L/TRAIL, gemcitabine or a combination of both therapies. RESULTS:
      Patient tumors grown as xenografts exhibited a spectrum of sensitivity to
      Apo2L/TRAIL. Both Apo2L/TRAIL sensitive and resistant pancreatic tumors were
      found, as well as tumors that showed heterogeneity of response. Changes in
      apoptotic signaling molecules in a sensitive tumor were analyzed by Western blot
      following Apo2L/TRAIL treatment; loss of procaspase 8, Bid and procaspase 3 was
      observed and correlated with inhibition of tumor growth. However, in a tumor that
      was highly resistant to killing by Apo2L/TRAIL, although there was a partial loss
      of procaspase 8 and Bid in response to Apo2L/TRAIL treatment, loss of procaspase
      3 was negligible. This resistant tumor also expressed a high level of the anti
      apoptotic molecule Bcl-XL that, in comparison, was not detected in a sensitive
      tumor. Importantly, in the majority of these tumors, addition of gemcitabine to
      Apo2L/TRAIL resulted in a greater anti-tumor effect than either therapy used
      alone. CONCLUSION: These data suggest that in a clinical setting we will see
      heterogeneity in the response of patients' tumors to Apo2L/TRAIL, including
      tumors that are highly sensitive as well as those that are resistant. While much
      more work is needed to understand the molecular basis for this heterogeneity, it
      is very encouraging, that Apo2L/TRAIL in combination with gemcitabine increased
      therapeutic efficacy in almost every case and therefore may be a highly effective
      strategy for controlling human pancreatic cancer validating and expanding upon
      what has been reported for cell lines.

PMID- 15943880
TI  - Conserved genomic organisation of Group B Sox genes in insects.
AB  - BACKGROUND: Sox domain containing genes are important metazoan transcriptional
      regulators implicated in a wide rage of developmental processes. The vertebrate B
      subgroup contains the Sox1, Sox2 and Sox3 genes that have early functions in
      neural development. Previous studies show that Drosophila Group B genes have been
      functionally conserved since they play essential roles in early neural
      specification and mutations in the Drosophila Dichaete and SoxN genes can be
      rescued with mammalian Sox genes. Despite their importance, the extent and
      organisation of the Group B family in Drosophila has not been fully
      characterised, an important step in using Drosophila to examine conserved aspects
      of Group B Sox gene function. RESULTS: We have used the directed cDNA sequencing
      along with the output from the publicly-available genome sequencing projects to
      examine the structure of Group B Sox domain genes in Drosophila melanogaster,
      Drosophila pseudoobscura, Anopheles gambiae and Apis mellifora. All of the insect
      genomes contain four genes encoding Group B proteins, two of which are
      intronless, as is the case with vertebrate group B genes. As has been previously
      reported and unusually for Group B genes, two of the insect group B genes, Sox21a
      and Sox21b, contain introns within their DNA-binding domains. We find that the
      highly unusual multi-exon structure of the Sox21b gene is common to the insects.
      In addition, we find that three of the group B Sox genes are organised in a
      linked cluster in the insect genomes. By in situ hybridisation we show that the
      pattern of expression of each of the four group B genes during embryogenesis is
      conserved between D. melanogaster and D. pseudoobscura. CONCLUSION: The DNA
      binding domain sequences and genomic organisation of the group B genes have been
      conserved over 300 My of evolution since the last common ancestor of the
      Hymenoptera and the Diptera. Our analysis suggests insects have two Group B1
      genes, SoxN and Dichaete, and two Group B2 genes. The genomic organisation of
      Dichaete and another two Group B genes in a cluster, suggests they may be under
      concerted regulatory control. Our analysis suggests a simple model for the
      evolution of group B Sox genes in insects that differs from the proposed
      evolution of vertebrate Group B genes.

PMID- 15943881
TI  - Foot pressure distribution during walking in young and old adults.
AB  - BACKGROUND: Measurement of foot pressure distribution (FPD) is clinically useful
      for evaluation of foot and gait pathologies. The effects of healthy aging on FPD
      during walking are not well known. This study evaluated FPD during normal walking
      in healthy young and elderly subjects. METHODS: We studied 9 young (30 +/- 5.2
      years), and 6 elderly subjects (68.7 +/- 4.8 years). FPD was measured during
      normal walking speed using shoe insoles with 99 capacitive sensors. Measured
      parameters included gait phase characteristics, mean and maximum pressure and
      force, and relative load.Time-series measurements of each variable for all
      sensors were grouped into 9 anatomical masks. RESULTS: Elderly subjects had lower
      normalized maximum pressure for the medial and lateral calcaneal masks, and for
      all medial masks combined. In the medial calcaneus mask, the elderly group also
      had a lower absolute maximum and lower mean and normalized mean pressures and
      forces, compared to young subjects. Elderly subjects had lower maximum force and
      normalized maximum force and lower mean force and normalized mean forces in the
      medial masks as well. CONCLUSION: FPD differences between the young and elderly
      groups were confined to the calcaneus and hallux regions and to the medial side
      of the foot. In elderly subjects, weight bearing on the lateral side of the foot
      during heel touch and toe-off phases may affect stability during walking.

PMID- 15943882
TI  - Self-rated health in Pakistan: results of a national health survey.
AB  - BACKGROUND: Self-rated health (SRH) is a robust predictor of mortality. In UK,
      migrants of South Asian descent, compared to native Caucasian populations, have
      substantially poorer SRH. Despite its validation among migrant South Asian
      populations and its popularity in developed countries as a useful public health
      tool, the SRH scale has not been used at a population level in countries in South
      Asia. We determined the prevalence of and risk factors for poor/fair SRH among
      individuals aged > or =15 years in Pakistan (n = 9442). METHODS: The National
      Health Survey of Pakistan was a cross-sectional population-based survey,
      conducted between 1990 and 1994, of 18,135 individuals aged 6 months and above;
      9442 of them were aged > or =15 years. Our main outcome was SRH which was
      assessed using the question: "Would you say your health in general is excellent,
      very good, good, fair, or poor?" SRH was dichotomized into poor/fair, and good
      (excellent, very good, or good). RESULTS: Overall 65.1% respondents -- 51.3 % men
      vs. 77.2 % women -- rated their health as poor/fair. We found a significant
      interaction between sex and age (p < 0.0001). The interaction was due to the
      gender differences only in the ages 15-19 years, whereas poor/fair SRH at all
      older ages was more prevalent among women and increased at the same rate as it
      did among men. We also found province of dwelling, low or middle SES, literacy,
      rural dwelling and current tobacco use to be independently associated with
      poor/fair SRH. CONCLUSION: This is the first study reporting on poor/fair SRH at
      a population-level in a South Asian country. The prevalence of poor/fair health
      in Pakistan, especially amongst women, is one of the worst ever reported,
      warranting immediate attention. Further research is needed to explain why women
      in Pakistan have, at all ages, poorer SRH than men.

PMID- 15943883
TI  - Estimating haplotype frequencies in pooled DNA samples when there is genotyping
      error.
AB  - BACKGROUND: Maximum likelihood estimates of haplotype frequencies can be obtained
      from pooled DNA using the expectation maximization (EM) algorithm. Through
      simulation, we investigate the effect of genotyping error on the accuracy of
      haplotype frequency estimates obtained using this algorithm. We explore model
      parameters including allele frequency, inter-marker linkage disequilibrium (LD),
      genotyping error rate, and pool size. RESULTS: Pool sizes of 2, 5, and 10
      individuals achieved comparable levels of accuracy in the estimation procedure.
      Common marker allele frequencies and no inter-marker LD result in less accurate
      estimates. This pattern is observed regardless of the amount of genotyping error
      simulated. CONCLUSION: Genotyping error slightly decreases the accuracy of
      haplotype frequency estimates. However, the EM algorithm performs well even in
      the presence of genotyping error. Overall, pools of 2, 5, and 10 individuals
      yield similar accuracy of the haplotype frequency estimates, while reducing costs
      due to genotyping.

PMID- 15943884
TI  - SuperLigands - a database of ligand structures derived from the Protein Data
      Bank.
AB  - BACKGROUND: Currently, the PDB contains approximately 29,000 protein structures
      comprising over 70,000 experimentally determined three-dimensional structures of
      over 5,000 different low molecular weight compounds. Information about these PDB
      ligands can be very helpful in the field of molecular modelling and prediction,
      particularly for the prediction of protein binding sites and function.
      DESCRIPTION: Here we present an Internet accessible database delivering PDB
      ligands in the MDL Mol file format which, in contrast to the PDB format, includes
      information about bond types. Structural similarity of the compounds can be
      detected by calculation of Tanimoto coefficients and by three-dimensional
      superposition. Topological similarity of PDB ligands to known drugs can be
      assessed via Tanimoto coefficients. CONCLUSION: SuperLigands supplements the set
      of existing resources of information about small molecules bound to PDB
      structures. Allowing for three-dimensional comparison of the compounds as a novel
      feature, this database represents a valuable means of analysis and prediction in
      the field of biological and medical research.

PMID- 15943886
TI  - Fatal meningitis in a previously healthy young adult caused by Streptococcus
      pneumoniae serotype 38: an emerging serotype?
AB  - BACKGROUND: In December 2001, a fatal case of pneumococcal meningitis in a Marine
      Corps recruit was identified. As pneumococcal vaccine usage in recruit
      populations is being considered, an investigation was initiated into the
      causative serotype. CASE PRESENTATION: Traditional and molecular methods were
      utilized to determine the serotype of the infecting pneumococcus. The
      pneumococcal isolate was identified as serotype 38 (PS38), a serotype not covered
      by current vaccine formulations. The global significance of this serotype was
      explored in the medical literature, and found to be a rare but recognized cause
      of carriage and invasive disease. CONCLUSION: The potential of PS38 to cause
      severe disease is documented in this report. Current literature does not support
      the hypothesis that this serotype is increasing in incidence. However, as we
      monitor the changing epidemiology of pneumococcal illness in the US in this
      conjugate era, PS38 might find a more prominent and concerning niche as a
      replacement serotype.

PMID- 15943885
TI  - APOBEC3G targets human T-cell leukemia virus type 1.
AB  - BACKGROUND: Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G
      (APOBEC3G) is a host cellular protein with a broad antiviral activity. It
      inhibits infectivitiy of a wide variety of retroviruses by deaminating
      deoxycytidine (dC) into deoxyuridine (dU) in newly synthesized minus strand DNA,
      resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the
      mechanism of its function, we have examined the antiviral activity of APOBEC3G on
      human T-cell leukemia virus type 1 (HTLV-1), the first identified human
      retrovirus. RESULTS: In this study, we have demonstrated that overexpressed as
      well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that
      APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive
      mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced
      by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human
      immunodeficiency virus type 1 (HIV-1) vif gene into HTLV-1 producing cell line,
      MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion
      incorporation, which resulted in upregulation of the infectivity of produced
      viruses. CONCLUSION: APOBEC3G is incorporated into HTLV-1 virions and inhibits
      the infection of HTLV-1 without exerting its cytidine deaminase activity. These
      results suggest that APOBEC3G might act on HTLV-1 through different mechanisms
      from that on HIV-1 and contribute to the unique features of HTLV-1 infection and
      transmission.

PMID- 15943887
TI  - Localization of plasma membrane t-SNAREs syntaxin 2 and 3 in intracellular
      compartments.
AB  - BACKGROUND: Membrane fusion requires the formation of a complex between a vesicle
      protein (v-SNARE) and the target membrane proteins (t-SNAREs). Syntaxin 2 and 3
      are t-SNAREs that, according to previous over-expression studies, are
      predominantly localized at the plasma membrane. In the present study we
      investigated localization of the endogenous syntaxin 2 and 3. RESULTS: Endogenous
      syntaxin 2 and 3 were found in NRK cells in intracellular vesicular structures in
      addition to regions of the plasma membrane. Treatment of these cells with N
      ethylmaleimide (NEM), which is known to inactivate membrane fusion, caused
      syntaxin 3 to accumulate in the trans-Golgi network and syntaxin 2 in perinuclear
      membrane vesicles. Kinetic analysis in the presence of NEM indicated that this
      redistribution of syntaxin 2 and 3 takes place via actin containing structures.
      CONCLUSION: Our data suggest that syntaxin 2 cycles between the plasma membrane
      and the perinuclear compartment whereas syntaxin 3 cycles between the plasma
      membrane and the trans-Golgi network. It is possible that this cycling has an
      important role in the regulation of t-SNARE function.

PMID- 15943888
TI  - Prognostic value of interleukin-1 receptor antagonist gene polymorphism and
      cytomegalovirus seroprevalence in patients with coronary artery disease.
AB  - BACKGROUND: Chronic inflammatory stimuli such as cytomegalovirus (CMV) infection
      and various genetic polymorphisms determining the inflammatory response are
      assumed to be important risk factors in atherosclerosis. We investigated whether
      patients with stable coronary artery disease (CAD) and homozygous for allele 2 of
      the interleukin 1 receptor antagonist (IL-1RA) gene and seropositive for CMV
      represent a group particular susceptible for recurrent cardiovascular events.
      METHODS: In a series of 300 consecutive patients with angiographically defined
      CAD a prospective follow-up was conducted (mean age 57.9 years, median follow-up
      time 38.2 months). RESULTS: No statistically significant relationship was found
      between CMV serostatus and IL-1RN*2 (alone or in combination) and risk for future
      cardiovascular events (CVE). The hazard ratio (HR) for a CVE given positive CMV
      serology and IL-1RN*2 was 1.07 (95% confidence interval (CI) 0.32-3.72) in the
      fully adjusted model compared to seronegative CMV patients not carrying the IL
      1RN*2 allele. In this prospective cohort study involving 300 patients with
      angiographically defined CAD at baseline, homozygosity for allele 2 of the IL-1
      RA and seropositivity to CMV alone and in combination were not associated with an
      increased risk for cardiovascular events during follow-up; in addition,
      combination of the CMV-seropositivity and IL-1RN*2 allele were not associated
      with a proinflammatory response. CONCLUSION: Our study suggests that
      seropositivity to CMV and IL-1RA*2 genotype alone or in combination might not be
      a strong risk factor for recurrent cardiovascular events in patients with
      manifest CAD, and is not associated with levels of established inflammatory
      markers.

PMID- 15943890
TI  - The ANITA trial seals the deal for adjuvant therapy in non-small-cell lung
      cancer.

PMID- 15943889
TI  - Vitrectomy with complete posterior hyaloid removal for ischemic central retinal
      vein occlusion: series of cases.
AB  - BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular
      disorder with potentially complications: (1) persistent macular edema and (2)
      neovascular glaucoma. No safe treatment exists that promotes the return of lost
      vision. Eyes with CRVO may be predisposed to vitreous degeneration. It has been
      suggested that if the vitreous remains attached to the macula owing to a firm
      vitreomacular adhesion, the resultant vitreous traction can cause inflammation
      with retinal capillary dilation, leakage and subsequent edema6. The roll of
      vitrectomy in ischemic CRVO surgical procedures has not been evaluated. CASE
      PRESENTATION: This is a non comparative, prospective, longitudinal, experimental
      and descriptive series of cases. Ten eyes with ischemic CRVO. Vitrectomy with
      complete posterior hyaloid removal was performed. VA, rubeosis, intraocular
      pressure (IOP), and macular edema were evaluated clinically. Multifocal ERG (m
      ERG), fluorescein angiography (FAG) and optic coherence tomography (OCT) were
      performed. Follow-up was at least 6 months. Moderate improvement of visual acuity
      was observed in 60% eyes and stabilized in 40%. IOP changed from 15.7 +/- 3.05
      mmHg to 14.9 +/- 2.69 mmHg post-operative and macular edema from 976 +/- 196
      microm to 640 +/- 191 microm to six month. The P1 wave amplitude changed from
      25.46 +/- 12.4 mV to 20.54 +/- 11.2 mV. CONCLUSION: A solo PPV with posterior
      hyaloid removal may help to improve anatomic and functional retina conditions in
      some cases. These results should be considered when analyzing other surgical
      maneuvers.

PMID- 15943892
TI  - Role of epidermal growth factor receptor mutations in predicting sensitivity or
      resistance to targeted agents in non-small-cell lung cancer.

PMID- 15943893
TI  - Updated data from the Iressa survival in lung cancer trial.

PMID- 15943894
TI  - A pilot trial of gefitinib in combination with docetaxel in patients with locally
      advanced or metastatic non-small-cell lung cancer.
AB  - Despite improvements in conventional treatment, patients with advanced non-small
      cell lung cancer (NSCLC) have a poor prognosis, leaving a significant unmet need
      for novel treatments. One such novel, biologically targeted agent is the orally
      active epidermal growth factor receptor tyrosine kinase inhibitor gefitinib. This
      open-label pilot trial investigated the safety, pharmacokinetics, and efficacy of
      2 doses of gefitinib (250 and 500 mg per day) combined with docetaxel (75 mg/m2)
      in patients with locally advanced or metastatic NSCLC as first- and second-line
      chemotherapy. Eighteen patients were recruited: 6 received gefitinib 250 mg per
      day plus docetaxel; 12 received gefitinib 500 mg per day plus docetaxel.
      Combination therapy was feasible with no overlapping toxicities. No patients
      experienced dose-limiting toxicities (DLTs) at 250 mg per day; 1 patient had 2
      DLT events at 500 mg per day (grade 3 rash and diarrhea for >4 days). Adverse
      events were mild to moderate, including fatigue, mucositis, nausea, anorexia,
      rash, diarrhea, and fever. Docetaxel did not appear to alter steady-state
      exposure to gefitinib. The effect of gefitinib on exposure to docetaxel was
      equivocal; with the exception of 2 patients in the gefitinib 250 mg per day dose
      group, there appeared to be no trend toward a higher or lower exposure to
      docetaxel when given in the presence of gefitinib compared with that when given
      alone. Combination therapy was associated with antitumor activity and responses
      were seen with gefitinib in 2 of 6 patients at 250 mg per day and 4 of 12
      patients at 500 mg per day. This combination is feasible and has an acceptable
      and predictable safety profile, as well as associated antitumor activity.

PMID- 15943895
TI  - Dose-intensive thoracic radiation therapy for patients at high risk with early
      stage non-small-cell lung cancer.
AB  - Recent studies suggest that radiation therapy (RT) dose escalation in early-stage
      non-small-cell lung cancer (NSCLC) is feasible when 3-dimensional therapy is
      used. However, the accompanying prolongation of the treatment course when
      standard fractionation is used could be suboptimal from a practical and biologic
      standpoint. We report results of a compressed course of RT for patients with
      pathologically documented clinical stage 1 NSCLC who were unsuitable for curative
      surgery because of pulmonary dysfunction or other medical comorbidities. Thirty
      one lesions were treated with dose-intensive RT (eg, fraction>or=2.25 Gy and
      nominal total dose>or=60 Gy) and have been followed up for >or=6 months from the
      completion of treatment. All patients completed therapy without interruption.
      Three patients developed grade 3 pulmonary toxicity 1-3 months after therapy. The
      overall tumor response rate was 88% (35% complete response and 53% partial
      response), whereas in-field tumor progression was documented for 5 of 31 lesions.
      Actuarial median survival was 38 months and 3-year overall survival was 60%, and
      most deaths were secondary to intercurrent disease. Moderately accelerated single
      daily fractionated RT is feasible for high-risk patients with early-stage NSCLC
      and merits further investigation.

PMID- 15943896
TI  - Limited-stage small-cell lung cancer (stages I-III): observations from the
      National Cancer Data Base.
AB  - The standard treatment of limited-stage small-cell lung cancer (LS-SCLC) has
      changed over the past 15 years. Standard treatment for LS-SCLC currently involves
      multiple-agent chemotherapy and early concurrent thoracic radiation therapy. Four
      patient cohorts (total number of patients, 22,969) diagnosed with LS-SCLC in 1985
      (N=2123), 1990 (N=6279), 1995 (N=7815), and 2000 (N=6752) were studied in order
      to describe demographic and treatment pattern changes as well as 5-year survival
      rates across cohorts. Women composed 40.2% of patients in the 1985 cohort but
      represented a significant proportional increase over each successive cohort,
      representing 50.8% of the 2000 cohort. The proportion of patients aged >or=70
      years also significantly increased over time, from 31.6% in 1985 to 44.9% in 2000
      (P<0.001). Over these years, the use of chemoradiation as the primary treatment
      for patients with LS-SCLC increased from 34.6% to 51.9% (from 37% to 60.5% for
      patients aged <70 years, and from 29.5% to 41.3% for patients aged >or=70 years).
      During the same time, the use of chemotherapy as the sole treatment decreased
      from 30.7% in 1985 to 21.7% in 2000. Chemotherapy as the sole treatment was used
      in 25.9% of the population>or=70 years of age in 2000, compared with 18.3% in
      patients aged <70 years. The percent of patients for which there was no treatment
      given did not change significantly between the cohorts (14.3% in 1985 and 13.7%
      in 2000; P<0.001). The 5-year survival rates and 95% confidence intervals (CIs)
      for the 1985, 1990, and 1995 cohorts of all ages of patients treated with
      chemoradiation therapy are as follows: 10.5% (CI, 6.75%-14.25%), 11.88% (CI,
      9.63%-14.13%), and 13.3% (CI, 11.2%-15.4%). Between 1985 and 2000 there was a
      significant increase in the percentage of women diagnosed with LS-SCLC. The use
      of combined chemotherapy and radiation therapy also increased during this period.
      This increase in chemoradiation therapy was associated with a decreased use of
      chemotherapy alone. Despite changes in demographics and treatment during these
      time intervals, the 5-year survival for patients with LS-SCLC treated with
      chemoradiation therapy did not increase significantly. These results demonstrate
      the continued need for the evaluation of new treatments in this group of
      patients.

PMID- 15943898
TI  - Long-term survival in a patient with stage IV non-small-cell lung carcinoma after
      bone metastasectomy.
AB  - Patients with bone metastases related to non-small-cell lung cancer (NSCLC) have
      a poor prognosis. In the rare situation in which a patient has a solitary bone
      metastasis, aggressive treatment may be warranted, as illustrated by the case
      reported here.

PMID- 15943897
TI  - A phase I/II study of exisulind in combination with docetaxel/carboplatin in
      patients with metastatic non-small-cell lung cancer.
AB  - Exisulind is a sulfone derivative of sulindac that induces apoptosis and
      demonstrates synergy with docetaxel in lung cancer models. This study evaluated
      the safety, efficacy, and pharmacokinetic interactions of exisulind and
      docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer
      (NSCLC). Fifty-seven patients received 218 cycles of docetaxel (75 mg/m2) and
      carboplatin (area under the curve, 5.0) in combination with exisulind (125-250 mg
      orally twice daily). Two complete responses and 9 partial responses were observed
      among the 47 patients assessable for response (overall response rate, 23%). The
      median duration of response was 5.9 months and median survival was 9.4 months.
      The 1- and 2-year survival rates are 35% and 14%, respectively. The hematologic
      toxicities were consistent with those previously reported with
      docetaxel/carboplatin. The most common nonhematologic toxicities were mild to
      moderate fatigue, anorexia, nausea, and vomiting. The addition of exisulind to
      the chemotherapy regimen did not interfere with the metabolism or elimination of
      docetaxel and vice versa, and docetaxel did not interfere with the
      pharmacokinetic parameters of exisulind. This trial did not allow direct
      comparison of patients receiving docetaxel/carboplatin with and without
      exisulind, but when compared with historical data of docetaxel/carboplatin alone,
      the addition of exisulind does not appear to enhance antitumor activity, duration
      of response, or survival. Although preclinical data demonstrate increased
      apoptosis and prolonged survival for the combination of exisulind and docetaxel,
      multiple clinical trials do not support further clinical development of this
      combination regimen in patients with advanced NSCLC.

PMID- 15943900
TI  - Structure and function of HtrA family proteins, the key players in protein
      quality control.
AB  - High temperature requirement A (HtrA) and its homologues constitute the HtrA
      family proteins, a group of heat shock-induced serine proteases. Bacterial HtrA
      proteins perform crucial functions with regard to protein quality control in the
      periplasmic space, functioning as both molecular chaperones and proteases. In
      contrast to other bacterial quality control proteins, including ClpXP, ClpAP, and
      HslUV, HtrA proteins contain no regulatory components or ATP binding domains.
      Thus, they are commonly referred to as ATP-independent chaperone-proteases.
      Whereas the function of ATP-dependent chaperone-proteases is regulated by ATP
      hydrolysis, HtrA exhibits a PDZ domain and a temperature-dependent switch
      mechanism, which effects the change in its function from molecular chaperone to
      protease. This mechanism is also related to substrate recognition and the fine
      control of its function. Structural and biochemical analyses of the three HtrA
      proteins, DegP, DegQ, and DegS, have provided us with clues as to the functional
      regulation of HtrA proteins, as well as their roles in protein quality control at
      atomic scales. The objective of this brief review is to discuss some of the
      recent studies which have been conducted regarding the structure and function of
      these HtrA proteins, and to compare their roles in the context of protein quality
      control.

PMID- 15943899
TI  - Molecular chaperones in protein quality control.
AB  - Proteins must fold into their correct three-dimensional conformation in order to
      attain their biological function. Conversely, protein aggregation and misfolding
      are primary contributors to many devastating human diseases, such as prion
      mediated infections, Alzheimer's disease, type II diabetes and cystic fibrosis.
      While the native conformation of a polypeptide is encoded within its primary
      amino acid sequence and is sufficient for protein folding in vitro, the situation
      in vivo is more complex. Inside the cell, proteins are synthesized or folded
      continuously; a process that is greatly assisted by molecular chaperones.
      Molecular chaperones are a group of structurally diverse and mechanistically
      distinct proteins that either promote folding or prevent the aggregation of other
      proteins. With our increasing understanding of the proteome, it is becoming clear
      that the number of proteins that can be classified as molecular chaperones is
      increasing steadily. Many of these proteins have novel but essential cellular
      functions that differ from that of more "conventional" chaperones, such as Hsp70
      and the GroE system. This review focuses on the emerging role of molecular
      chaperones in protein quality control, i.e. the mechanism that rids the cell of
      misfolded or incompletely synthesized polypeptides that otherwise would interfere
      with normal cellular function.

PMID- 15943901
TI  - Protein folding and diseases.
AB  - For most of proteins to be active, they need well-defined three-dimensional
      structures alone or in complex. Folding is a process through which newly
      synthesized proteins get to the native state. Protein folding inside cells is
      assisted by various chaperones and folding factors, and misfolded proteins are
      eliminated by the ubiquitin-proteasome degradation system to ensure high fidelity
      of protein expression. Under certain circumstances, misfolded proteins escape the
      degradation process, yielding to deposit of protein aggregates such as loop-sheet
      polymer and amyloid fibril. Diseases characterized by insoluble deposits of
      proteins have been recognized for long time and are grouped as conformational
      diseases. Study of protein folding mechanism is required for better understanding
      of the molecular pathway of such conformational diseases.

PMID- 15943902
TI  - Distinct differences between TNF receptor 1- and TNF receptor 2-mediated
      activation of NFkappaB.
AB  - Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors,
      TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and
      biological roles. In the present study, TNFR2 and TNFR1 signal transduction
      mechanisms involved in activation of NFkappaB and CMV promoter-enhancer were
      compared with respect to their susceptibility towards inhibitors of intracellular
      signaling. For this, we used SW480 cells, where we have shown that TNF-signaling
      can occur independently through each of the two receptors. The TNFR1 response was
      inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA),
      and by sodium salicylate, while TNFR2-mediated activation of NFkappaB and CMV
      promoter-enhancer was resistant to these compounds. The signaling mechanisms
      known to be affected by these inhibitors include phospholipases as well as redox-
      and pH-sensitive intracellular components. Our results imply that TNFR2 signaling
      involved in NFkappaB activation proceeds independently of these inhibitor
      sensitive signaling components, indicating distinct signaling pathways not shared
      with TNFR1.

PMID- 15943903
TI  - Screening of the antigen epitopes of basic fibroblast growth factor by phage
      display.
AB  - In order to investigate the epitope of basic fibroblast growth factor (bFGF) and
      its immunogenicity, the epitopes of bFGF were screened from the phage display
      library with monoclonal antibody GF22, which can neutralize the bio-activity of
      bFGF. By three rounds of screening, the positive phage clones with bFGF epitopes
      were selected, which can effectively block the bFGF to bind with GF22. Sequence
      analysis showed that the epitopes shared a highly conservative sequence (Leu-Pro
      Pro/Leu-Gly-His-Phe/Ile-Lys). The sequence of PPGHFK was located at 22-27 of the
      bFGF. The specific immuno-response of mouse could be highly induced by phage
      clones with the epitopes. And the anti-bFGF activity induced by LPGHFK was 3
      times higher than the original sequence, which showed that the mimetic peptide
      LPLGHIK might be used as a tumor vaccine in the prevention and treatment of
      tumor.

PMID- 15943904
TI  - Production of recombinant humanized anti-HBsAg Fab fragment from Pichia pastoris
      by fermentation.
AB  - In this report, we describe the high-yield secretory expression of the
      recombinant human anti-HBsAg Fab fragment from Pichia pastoris that was achieved
      by co-integration of the genes encoding the heavy and light chains (both under
      the control of alcohol oxidase promoter) into the genome of the yeast cells. The
      fed-batch fermentations were carried out in a 5 L scale. Both chains of the Fab
      were successfully expressed upon methanol induction. The absorbance (OD600) of
      the broth can reach 350 approximately 500 at the end of fed-batch phase. After
      the induction, the expression level of the recombinant Fab (soluble) reached 420
      approximately 458 mg/L. The recombinant Fab fragment was purified from the crude
      culture supernatant by ion exchange chromatography and the purity of the
      recombinant Fab fragment was over 95%. The affinity activities of the crude
      fermentation supernatant and the purified Fab were analyzed by indirect ELISA,
      which showed that the purified recombinant Fab fragment had high affinity
      activity with hepatitis B surface antigen.

PMID- 15943905
TI  - The effect of dimethyl dimethoxy biphenyl dicarboxylate (DDB) against tamoxifen
      induced liver injury in rats: DDB use is curative or protective.
AB  - Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast
      cancer. It showed a degree of hepatic carcinogenesis, when it used for long term
      as it can decrease the hexose monophosphate shunt and thereby increasing the
      incidence of oxidative stress in liver rat cells leading to liver injury. In this
      study, a model of liver injury in female rats was done by intraperitoneal
      injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days.
      This model produced a state of oxidative stress accompanied with liver injury as
      noticed by significant declines in the antioxidant enzymes (glutathione-S
      transferase, glutathione peroxidase and catalase) and reduced glutathione
      concomitant with significant elevations in TBARS (thiobarbituric acid reactive
      substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase)
      and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral
      administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of
      200 mg/kg body weight daily for 10 successive days, resulted in alleviation of
      the oxidative stress status of tamoxifen-intoxicated liver injury in rats as
      observed by significant increments in the antioxidant enzymes (glutathione-S
      transferase, glutathione peroxidase and catalase) and reduced glutathione
      concomitant with significant decrements in TBARS and liver transaminases; sGPT
      and sGOT levels. The administration of DDB before tamoxifen intoxication (as
      protection) is more little effective than its curative effect against tamoxifen
      induced liver injury. The data obtained from this study speculated that DDB can
      mediate its biochemical effects through the enhancement of the antioxidant enzyme
      activities and reduced glutathione level as well as decreasing lipid peroxides.

PMID- 15943906
TI  - Preliminary proteomic analysis of Thiobacillus ferrooxidans growing on elemental
      sulphur and Fe2+ separately.
AB  - Thiobacillus ferrooxidans is one of the most important bacterium used in
      bioleaching, and can utilize Fe2+ or sulphide as energy source. Growth curves for
      Thiobacillus ferrooxidans have been tested, which show lag, logarithmic,
      stationary and aging phases as seen in other bacteria. The logarithmic phases
      were from 10 to 32 hours for Thiobacillus ferrooxidans cultivated with Fe2+ and
      from 4 to 12 days for Thiobacillus ferrooxidans cultivated with elemental
      sulphur. Differences of protein patterns of Thiobacillus ferrooxidans growing on
      elemental sulphur and Fe2+ separately were investigated after cultivation at 30
      degrees C by the analysis of two-dimensional gel electrophoresis (2-DE), matrix
      assisted laser desorption/ ionization (MALDI)-Mass spectrometry and ESI-MS/MS.
      From the 17 identified protein spots, 11 spots were found more abundant when
      growing on elemental sulphur. By contrast 6 protein spots were found decreased at
      elemental cultivation condition. Among the proteins identified, cytochrome C have
      been previously identified as necessary elements of electron-transferring pathway
      for Thiobacillus ferrooxidans to oxidize Fe2+; ATP synthase alpha chain and beta
      are expressed increased when Thiobacillus ferrooxidans cultivated with Fe2+ as
      energy source. ATP synthase Beta chain is the catalytic subunit, and ATP synthase
      alpha chain is a regulatory subunit. The function of ATPase produces ATP from ADP
      in the presence of a proton gradient across the membrane.

PMID- 15943907
TI  - Adenosine induced apoptosis in BHK cells via P1 receptors and equilibrative
      nucleoside transporters.
AB  - Adenosine, as a ubiquitous metabolite, mediates many physiological functions via
      activation of plasma membrane receptors. Mechanisms of most of its physiological
      roles have been studied extensively, but research on adenosine-induced apoptosis
      (AIA) has only started recently. In this study we demonstrate that adenosine dose
      dependently triggered apoptosis of cultured baby hamster kidney (BHK) cells.
      Adenosine-induced apoptotic cell death was characterized by DNA laddering,
      changes in nuclear chromatin morphology and phosphatidylserine staining.
      Apoptosis was also quantified by flow cytometry. Results suggest the involvement
      of adenosine A1 and A3 receptors as well as equilibrative nucleoside transporters
      in apoptosis induced by adenosine. These results indicate a receptor-transporter
      co-signaling mechanism in AIA in BHK cells. The involvement of A1 and A3
      receptors also implies a possible apoptotic pathway mediated by G protein-coupled
      receptors.

PMID- 15943908
TI  - Hybrid 'Sinta' papaya exhibits unique ACC synthase 1 cDNA isoforms.
AB  - Five ripening-related ACC synthase cDNA isoforms were cloned from 80% ripe papaya
      cv. 'Sinta' by reverse transcription-PCR using gene-specific primers. Clone 2 had
      the longest transcript and contained all common exons and three alternative
      exons. Clones 3 and 4 contained common exons and one alternative exon each, while
      clone 1, the most common transcript, contained only the common exons. Clone 5
      could be due to cloning artifacts and might not be a unique cDNA fragment. Thus,
      there are only four isoforms of ACC synthase mRNA. Southern blot analysis
      indicates that all five clones came from only one gene existing as a single copy
      in the 'Sinta' papaya genome. Multiple sequence alignment indicates that the four
      isoforms arise from a single gene, possibly through alternative splicing
      mechanisms. All the putative alternative exons were present at the 5'-end of the
      gene comprising the N-terminal region of the protein. 'Sinta' ACC synthase cDNAs
      were of the capacs 1 type and are most closely related to a 1.4 kb capacs 1-type
      DNA (AJ277160) from Eksotika papaya. No capacs 2-type cDNAs were cloned from
      'Sinta' by RT-PCR. This is the first report of possible alternative splicing
      mechanism in ripening-related ACC synthase genes in hybrid papaya, possibly to
      modulate or fine-tune gene expression relevant to fruit ripening.

PMID- 15943909
TI  - Expression of Sara2 human gene in erythroid progenitors.
AB  - A human homologue of Sar1, named Sara2, was shown to be preferentially expressed
      during erythropoiesis in a culture stimulated by EPO. Previous studies, in yeast,
      have shown that secretion-associated and Ras-related protein (Sar1p) plays an
      essential role in protein transport from the endoplasmic reticulum to the Golgi
      apparatus. Here, we report the molecular analysis of Sara2 in erythroid cell
      culture. A 1250 bp long cDNA, encoding a 198 amino-acid protein very similar to
      Sar1 proteins from other organisms, was obtained. Furthermore, we also report a
      functional study of Sara2 with Real-time quantitative PCR analysis, demonstrating
      that expression of Sara2 mRNA increases during the initial stages of erythroid
      differentiation with EPO and that a two-fold increase in expression occurs
      following the addition of hydroxyurea (HU). In K562 cells, Sara2 mRNA was
      observed to have a constant expression and the addition of HU also up-regulated
      the expression in these cells. Our results suggest that Sara2 is an important
      gene in processes involving proliferation and differentiation and could be
      valuable for understanding the vesicular transport system during erythropoiesis.

PMID- 15943910
TI  - Induction of peripheral tolerance in dual TCR T cells: an evidence for non
      dominant signaling by one TCR.
AB  - Recently, the existence of T cells with dual T cell receptor (TCR) in the immune
      system is generally accepted, while it has been controversial whether signals
      through one TCR would affect the functions of the other. In this study T cells
      expressing two different TCR were obtained from cross-hybrids of LCMV and AND TCR
      transgenic mice specific for the gp33 and peptide fragment of PCC (fPCC),
      respectively. Peptide stimulation demonstrated that the dual TCR T cells
      functioned independently in an antigen-specific manner. To examine whether the
      tolerance targeted for the one TCR affects the responsiveness of the other, the
      cross-hybrids were treated with gp33. Although T cells from F1 mice were rendered
      anergenic to gp33, no functional changes to fPCC were observed in terms of
      cellular proliferation and IL-2 secretion, suggesting that the dual TCR T cells
      remained reactive to fPCC. We therefore propose that signaling through the TCR is
      receptor-specific and 'negative dominance' of one TCR by tolerance induction is
      not applicable in this dual TCR system.

PMID- 15943911
TI  - Activity determination, kinetic analyses and isoenzyme identification of gamma
      glutamyltransferase in human neutrophils.
AB  - Gamma-glutamyltransferase (GGT, EC 2.3.2.2) which hydrolyzes glutathione (GSH),
      is required for the maintenance of normal intracellular GSH concentration. GGT is
      a membrane enzyme present in leukocytes and platelets. Its activity has also been
      observed in human neutrophils. In this study, GGT was purified from Triton X-100
      solubilized neutrophils and its kinetic parameters were determined. For kinetic
      analyses of transpeptidation reaction, gamma-glutamyl p-nitroanilide was used as
      the substrate and glycylglycine as the acceptor. Apparent K(m) values were
      determined as 1.8 mM for gamma-glutamyl p-nitroanilide and 16.9 mM for
      glycylglycine. The optimum pH of GGT activity was 8.2 and the optimum temperature
      was 37 degrees C. It had thermal stability with 58 % relative activity at 56
      degrees C for 30 min incubation. L-serine, in the presence of borate, was
      detected as the competitive inhibitor. Bromcresol green inhibited neutrophil GGT
      activity as a noncompetitive inhibitor. The neutrophils seem to contain only the
      isoenzyme that is present in platelets. We characterized the kinetic properties
      and compared the type of the isoenzyme of neutrophil GGT with platelet GGT via
      polyacrylamide gel electrophoresis (PAGE) under a standard set of conditions.

PMID- 15943912
TI  - Study of alanine-73 and aspartate-9 of HLA-C locus in Saudi psoriasis patients,
      using sequence-specific primers (PCR-SSP).
AB  - Alanine at residue 73 (Ala-73) and aspartate at residue 9 (Asp-9) are
      characteristic to both Cw6 and Cw7 alleles of HLA-C gene and have been suggested
      as possible markers for psoriasis vulgaris (PsV). However, the results from
      various ethnic groups/populations are contradictory and inconclusive. In this
      study, an attempt has been made to examine the association between HLA-C (Ala-73
      and Asp-9) and susceptibility to PsV among Saudi patients. Genomic DNA was
      extracted from 25 Saudi PsV patients and 75 control subjects. Polymerase chain
      reaction (PCR) was performed to amplify HLA-C sequences using earlier reported
      primers, C133P and C243PR. Sequence-specific primers were used to specifically
      detect nucleotide coding for Ala-73 and Asp-9 in all the subjects. The results
      showed significantly higher frequency of Asp-9 (84.0 % versus 61.3 %) in PsV
      patients as compared to controls (p < 0.05, 2-tailed Fisher's exact test). The
      frequencies of Ala-73 among PsV patients (92 %) and controls (88 %) did not
      differ significantly.

PMID- 15943913
TI  - Characterization of Ha29, a specific gene for Helicoverpa armigera single
      nucleocapsid nucleopolyhedrovirus.
AB  - Open reading frame 29 (ha29) is a gene specific for Helicoverpa armigera single
      nucleocapsid nucleopolyhedrovirus (HearSNPV). Sequence analyses showed that the
      transcription factor Tfb2 motif, bromodomain and Half-A-TPR (HAT) repeat were
      present at aa 66-82, 4-76, 55-90 of the Ha29 protein respectively. The product of
      Ha29 was detected in HearSNPV-infected HzAM1 cells at 3 h post-infection. Western
      blot analysis using a polyclonal antibody produced by immunizing a rabbit with
      purified GST-Ha29 fusion protein indicates that Ha29 is an early gene. The size
      of Ha29 product in infected HzAM1 cells was about 25 kDa, which was larger than
      the presumed size of 20.4 kDa. Tunicamycin treatment of HearSNPV-infected HzAM1
      cells suggested that the Ha29 protein is N-glycosylated. Fluorescent confocal
      laser scanning microscope examination, and Western blot analysis of purified
      budded virus (BVs), occlusion-derived virus (ODVs), cell nuclear and cytoplasmic
      fraction, showed that the Ha29 protein was localized in the nucleus. Our results
      suggested that ha29 of HearSNPV encodes a non-structurally functional protein
      that may be associated with virus gene transcription in Helicoverpa hosts.

PMID- 15943914
TI  - Polyphosphoinositides are derived from ether-linked inositol glycerophospholipids
      in rat brain.
AB  - Membrane inositol glycerophospholipid (IGP) is metabolized to
      phosphatidylinositol-4-phosphate (PIP), phosphatidylinositol-4, 5-bisphosphate
      (PIP2), and inositol triphosphate (IP3) in signaling transduction. This study was
      carried out to determine the subclasses of IGP involved in signaling pathway. The
      acyl chain moieties of the phospholipids are easily modulated by dietary fatty
      acids. We analyzed acyl chain composition of IGP 3-subclasses, PIP and PIP2 from
      rat brain after feeding sunflower seed oil enriched with linoleic acid or fish
      oil high in eicosapentaenoic acid and docosahexaenoic acid. Long chain
      polyunsaturated fatty acids (LCPUFA) as eicosapentaenoic acid and docosahexaenoic
      acid were not incorporated into ether-linked IGP
      (alkenylacylglycerophosphoinositol and alkylacyl-glycerophosphoinositol), PIP and
      PIP2, while diacyl-glycerophosphoinositol (GPI) contained high LCPUFA. These
      results suggest that PIP might be phosphorylated from only the ether-linked IGP
      (alkenylacyl- and alkylacyl species) but not from diacyl subclass for signals to
      intracellular responses in the plasma membrane of rat brain.

PMID- 15943915
TI  - A continuous spectrophotometric assay for NADPH-cytochrome P450 reductase
      activity using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.
AB  - NADPH-cytochrome P450 reductase (CPR) transfers electrons from NADPH to
      cytochrome P450 and also catalyzes the one-electron reduction of many drugs and
      foreign compounds. Various spectrophotometric assays have been performed to
      examine electron-accepting properties of CPR and its ability to reduce cytochrome
      b5, cytochrome c, and ferricyanide. In this report, reduction of 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) by CPR has been
      assessed as a method for monitoring CPR activity. The principle advantage of this
      substance is that the reduction of MTT can be assayed directly in the reaction
      medium by a continuous spectrophotometric method. The electrons released from
      NADPH by CPR were transferred to MTT. MTT reduction activity was then assessed
      spectrophotometrically by measuring the increase of A610. MTT reduction followed
      classical Michaelis-Menten kinetics (K(m)= 20 microM, k(cat)= 1,910 min(-1)).
      This method offers the advantages of a commercially available substrate and short
      analysis time by a simple measurement of enzymatic activity of CPR.

PMID- 15943916
TI  - Cross-linked leucaena seed gum matrix: an affinity chromatography tool for
      galactose-specific lectins.
AB  - A cross-linked leucaena (Leucaena leucocephala) seed gum (CLLSG) matrix was
      prepared for the isolation of galactose-specific lectins by affinity
      chromatography. The matrix was evaluated for affinity with a known galactose
      specific lectin from the seeds of snake gourd (Trichosanthes anguina). The matrix
      preparation was simple and inexpensive when compared to commercial galactose
      specific matrices (i.e. about 1.5 US dollars/100 ml of matrix). The current
      method is also useful for the demonstration of the affinity chromatography
      technique in laboratories. Since leucaena seeds are abundant and inexpensive, and
      the matrix preparation is easy, CLLSG appears to be a promising tool for the
      separation of galactose-specific lectins.

PMID- 15943917
TI  - Investigation of three strategies for an international genetic evaluation of beef
      cattle weaning weight.
AB  - Weaning weights from 83,389 Limousin calves born between 1993 and 2002 in France
      and the Trans-Tasman block (Australia/New Zealand) were analysed to compare
      different strategies for running an international genetic evaluation for the
      breed. These records were a subset of the complete data for both countries and
      comprised a sample of herds that had recorded progeny of sires used across both
      countries. Genetic and phenotypic parameters for weaning weight were estimated
      within the countries. The estimates of direct genetic heritabilities were higher
      in France than in the Trans-Tasman block (0.31 vs. 0.22), while direct-maternal
      genetic correlations were less negative in the Trans-Tasman block (-0.10) than in
      France (-0.21). Different strategies for an international evaluation were
      studied, and the correlations between the estimated breeding values (EBV) of
      national evaluations and these strategies were derived. The international
      evaluation strategies were a) an animal model on raw performance data with non
      unity genetic correlations and heterogeneous residual and genetic variances
      across countries; b) the same animal model applied to pre-corrected (for fixed
      effects) performance data; and c) a sire model on de-regressed proofs (MACE).
      Estimates of the genetic correlations between weaning weight in both countries
      were 0.86 (0.80) for direct (maternal) genetic effects for the first strategy.
      Estimation of variance components by MACE appeared to be very sensitive to the
      sample of bulls and their reliability approximations. Variance component
      estimates obtained using pre-corrected data were inconsistent with estimates on
      raw data. However, the EBV predicted using pre-corrected data and parameters
      estimated from the raw data were similar to those predicted from raw data.
      Correlations between national and international EBV were always high (> 0.90) for
      sires, whichever genetic effect (direct or maternal) or international evaluation
      model was considered. The ranking of the bulls in the top 100 is of primary
      interest in terms of international genetic evaluation. In this study, some re
      ranking of sires was observed for the top 100 bulls between countries and between
      the three international evaluation models. Thus, the origin of top sires may vary
      according to the implemented international evaluation strategy.

PMID- 15943918
TI  - Genetic analysis of emotional reactivity in sheep: effects of the genotypes of
      the lambs and of their dams.
AB  - A total of 1347 weaned lambs from eight genotypes were tested over five
      consecutive years: Romanov (ROM) and Lacaune (LAC) pure breeds, the two F1
      crossbreeds (RL and LR) and the offspring of ewes from these four genotypes sired
      with Berrichon-du-Cher rams (BCF). The lambs were individually exposed to three
      challenging tests involving novelty, human contact and social isolation. Ten
      synthetic variables were used to express social reactivity (i.e., active vs.
      passive strategy), exploratory activity and reactivity to humans. BCF crossbreds
      were more active (i.e., high bleats, locomotion and attempts to escape) than
      purebreds and F1. In contrast, ROM expressed more passive responses (i.e., low
      bleats and vigilance postures) than LAC and BCF crossbreds. In addition, ROM
      approached a motionless human less and had longer flight distances to an
      approaching human than did LAC and BCF crossbreds. When restrained, ROM, and to a
      lesser extent B x ROM and B x LR, avoided human contact more than did LAC, RL and
      B x LAC. Most of these differences were explained by direct additive genetic
      effects while maternal influences or heterosis effects were rarely significant.
      The highest heritability was for high bleats (h2 = 0.48). Females were more
      active and avoided human contact more than did males.

PMID- 15943919
TI  - Using genotype probabilities in survival analysis: a scrapie case.
AB  - The objective was to evaluate the potential use of genotype probabilities to
      handle records of non-genotyped animals in the context of survival analysis. To
      do so, the risks associated with the PrP genotype and other transmission factors
      in relation to clinical scrapie were estimated. Data from 4049 Romanov sheep
      affected by natural scrapie were analyzed using survival analysis techniques. The
      original data set included 1310 animals with missing genotypes; five of those had
      uncensored records. Different missing genotype-information patterns were
      simulated for uncensored and censored records. Three strategies differing in the
      way genotype information was handled were tested. Firstly, records with unknown
      genotypes were discarded (P1); secondly, those records were grouped in an unknown
      class (P2). Finally the probabilities of genotypes were assigned (P3). Whatever
      the strategy, the ranking of relative risks for the most susceptible genotypes
      (VRQ-VRQ, ARQ-VRQ and ARQ-ARQ) was similar even when the non-genotyped animals
      were not a negligible part of uncensored records. However, P3 had a more
      efficient way of handling missing genotype information. As compared to P1, either
      P2 or P3 avoided discarding the records of non-genotyped animals; however, P3
      eliminated the unknown class and the risk associated with this group. Genotype
      probabilities were shown to be a useful technique to handle records of
      individuals with unknown genotype.

PMID- 15943920
TI  - Use of meta-analysis to combine candidate gene association studies: application
      to study the relationship between the ESR PvuII polymorphism and sow litter size.
AB  - This article investigates the application of meta-analysis on livestock candidate
      gene effects. The PvuII polymorphism of the ESR gene is used as an example. The
      association among ESR PvuII alleles with the number of piglets born alive and
      total born in the first (NBA1, TNB1) and later parities (NBA, TNB) is reviewed by
      conducting a meta-analysis of 15 published studies including 9329 sows. Under a
      fixed effects model, litter size values were significantly lower in the "AA"
      genotype groups when compared with "AB" and "BB" homozygotes. Under the random
      effects model, the results were similar although differences between "AA" and
      "AB" genotype groups were not clearly significant for NBA and TNB. Nevertheless,
      the most noticeable result was the high and significant heterogeneity estimated
      among studies. This heterogeneity could be assigned to error sampling, genotype
      by environment interaction, linkage or epistasis, as referred to in the
      literature, but also to the hypothesis of population admixture/stratification. It
      is concluded that meta-analysis can be considered as a helpful analytical tool to
      synthesise and discuss livestock candidate gene effects. The main difficulty
      found was the insufficient information on the standard errors of the estimated
      genotype effects in several publications. Consequently, the convenience of
      publishing the standard errors or the concrete P-values instead of the test
      significance level should be recommended to guarantee the quality of candidate
      gene effect meta-analyses.

PMID- 15943921
TI  - Genetic management of infectious diseases: a heterogeneous epidemio-genetic model
      illustrated with S. aureus mastitis.
AB  - Given that individuals are genetically heterogeneous in their degree of
      resistance to infection, a model is proposed to formulate appropriate choices
      that will limit the spread of an infectious disease. The model is illustrated
      with data on S. aureus mastitis and is based on parameters characterizing the
      spread of the disease (contact rate, probability of infection after contact, and
      rate of recovery after infection), the demography (replacement and culling rates)
      and the genetic composition (degree of relationship and heritability of the
      disease trait) of the animal population. To decrease infection pressure, it is
      possible to apply non-genetic procedures that increase the culling (e.g., culling
      of chronically infected cows) and recovery (e.g., antibiotic therapy) rates of
      infected cows. But the contribution of the paper is to show that genetic
      management of infectious disease is also theoretically possible as a control
      measure complementary to non-genetic actions. Indeed, the probability for an
      uninfected individual to become infected after contact with an infected one is
      partially related to their degree of kinship: the more closely they are related,
      the more likely they are to share identical genes like those associated to the
      non-resistance to infection. Different prospective genetic management procedures
      are proposed to decrease the contact rate between infected and uninfected
      relatives and keep the number of secondary cases generated by one infected animal
      below 1.

PMID- 15943922
TI  - Characterization of 35 novel microsatellite DNA markers from the duck (Anas
      platyrhynchos) genome and cross-amplification in other birds.
AB  - In order to study duck microsatellites, we constructed a library enriched for
      (CA)n, (CAG)n, (GCC)n and (TTTC)n. A total of 35 pairs of primers from these
      microsatellites were developed and used to detect polymorphisms in 31 unrelated
      Peking ducks. Twenty-eight loci were polymorphic and seven loci were monomorphic.
      A total of 117 alleles were observed from these polymorphic microsatellite
      markers, which ranged from 2 to 14 with an average of 4.18 per locus. The
      frequencies of the 117 alleles ranged from 0.02 to 0.98. The highest
      heterozygosity (0.97) was observed at the CAUD019 microsatellite locus and the
      lowest heterozygosity (0.04) at the CAUD008 locus, and 11 loci had
      heterozygosities greater than 0.50 (46.43%). The polymorphism information content
      (PIC) of 28 loci ranged from 0.04 to 0.88 with an average of 0.42. All the above
      markers were used to screen the polymorphism in other bird species. Two markers
      produced specific monomorphic products with the chicken DNA. Fourteen markers
      generated specific fragments with the goose DNA: 5 were polymorphic and 9 were
      monomorphic. But no specific product was detected with the peacock DNA. Based on
      sequence comparisons of the flanking sequence and repeat, we conclude that 2
      chicken loci and 14 goose loci were true homologous loci of the duck loci. The
      microsatellite markers identified and characterized in the present study will
      contribute to the genetic map, quantitative traits mapping, and phylogenetic
      analysis in the duck and goose.

PMID- 15943923
TI  - Dechlorination of hexachlorocyclohexanes with alkaline 2-propanol and a palladium
      catalyst.
AB  - Hexachlorocyclohexane isomers (alpha-, beta-, gamma- and delta-HCH) were
      dechlorinated in 2-propanol by means of stoichiometric reaction with NaOH and
      subsequent catalytic dechlorination over a supported palladium catalyst (Pd/C).
      When the HCH isomers (2-10 mmol/l) were reacted with a molar excess of NaOH
      ([NaOH]/[HCH]>9) in 2-propanol, transformation of alpha-, gamma- and delta-HCH to
      trichlorobenzenes (TCBs) was complete within 5 min at room temperature, but beta
      HCH was less reactive. Analysis of TCB isomers produced from individual HCH
      isomers showed that 1,2,4-TCB was always predominant (70-90% of the product) and
      1,2,3-TCB and 1,3,5-TCB were minor products. The produced TCBs were dechlorinated
      by subsequently adding Pd/C to the alkaline 2-propanol solution and heating at 55
      degrees C for 3 h, resulting in the formation of benzene in high yield (>80%).
      Technical-grade HCH, which contains these four isomers, was successfully
      dechlorinated with NaOH and Pd/C at 55 degrees C.

PMID- 15943924
TI  - Remediation of soil contaminated with the heavy metal (Cd2+).
AB  - Soil contamination by heavy metals is increasing. The biosorption process for
      removal of the heavy metal Cd(2+) from contaminated soil is chosen for this study
      due to its economy, commercial applications, and because it acts without
      destroying soil structure. The study is divided into four parts (1) soil
      leaching: the relationships between the soil leaching effect and agitation rates,
      solvent concentrations, ratios of soil to solvent, leaching time and pH were
      studied to identify their optimum conditions; (2) adsorption Cd(2+) tests of
      immobilized Saccharomycetes pombe beads: different weight percentages of chitosan
      and polyvinyl alcohol (PVAL) were added to alginate (10 wt.%) and then blended or
      cross-linked by epichlorohydrin (ECH) to increase their mechanical strength.
      Next, before blending or cross-linking, different weight percentages of S. pombe
      806 or S. pombe ATCC 2476 were added to increase Cd(2+) adsorption. Thus, the
      optimum beads (blending or cross-linking, the percentages of chitosan, PVAL and
      S. pombe 806 or S. pombe ATCC 2476) and the optimum adsorption conditions
      (agitation rate, equilibrium adsorption time, and pH in the aqueous solution)
      were ascertained; (3) regeneration tests of the optimum beads: the optimum beads
      adsorbing Cd(2+) were regenerated by various concentrations of aqueous HCl
      solutions. The results indicate that the reuse of immobilized pombe beads was
      feasible; and (4) adsorption model/kinetic model/thermodynamic property: the
      equilibrium adsorption, kinetics, change in Gibbs free energy of adsorption of
      Cd(2+) on optimum beads were also investigated.

PMID- 15943925
TI  - Multivariate analysis of selected metals in tannery effluents and related soil.
AB  - Effluent and relevant soil samples from 38 tanning units housed in Kasur,
      Pakistan, were obtained for metal analysis by flame atomic absorption
      spectrophotometric method. The levels of 12 metals, Na, Ca, K, Mg, Fe, Mn, Cr,
      Co, Cd, Ni, Pb and Zn were determined in the two media. The data were evaluated
      towards metal distribution and metal-to-metal correlations. The study evidenced
      enhanced levels of Cr (391, 16.7 mg/L) and Na (25,519, 9369 mg/L) in tannery
      effluents and relevant soil samples, respectively. The effluent versus soil trace
      metal content relationship confirmed that the effluent Cr was strongly correlated
      with soil Cr. For metal source identification the techniques of principal
      component analysis, and cluster analysis were applied. The principal component
      analysis yielded two factors for effluents: factor 1 (49.6% variance) showed
      significant loading for Ca, Fe, Mn, Cr, Cd, Ni, Pb and Zn, referring to a tanning
      related source for these metals, and factor 2 (12.6% variance) with higher
      loadings of Na, K, Mg and Co, was associated with the processes during the
      skin/hide treatment. Similarly, two factors with a cumulative variance of 34.8%
      were obtained for soil samples: factor 1 manifested the contribution from Mg, Mn,
      Co, Cd, Ni and Pb, which though soil-based is basically effluent-derived, while
      factor 2 was found associated with Na, K, Ca, Cr and Zn which referred to a
      tannery-based source. The dendograms obtained from cluster analysis, also support
      the observed results. The study exhibits a gross pollution of soils with Cr at
      levels far exceeding the stipulated safe limit laid down for tannery effluents.

PMID- 15943926
TI  - Occurrence and distribution of polycyclic aromatic hydrocarbons in reclaimed
      water and surface water of Tianjin, China.
AB  - Persistent organic pollutants (POPs) such as polycyclic aromatic hydrocarbons
      (PAHs) are of great concern due to their persistence, bioaccumulation and toxic
      effects. In this work, 16 PAHs included in the US Environmental Protection
      Agency's (EPA) priority pollutant list were analyzed using solid-phase extraction
      gas chromatography-mass spectrometry (SPE-GC-MS) with a selected ion monitoring
      (SIM) mode. Reclaimed water and surface water sampling was undertaken in Tianjin,
      northern China. Total PAH concentrations varied from 1800 to 35,000 ng/L in
      surface waters (main rivers, tributaries, ditches, etc.) with mean value of
      14,000 ng/L and from 227 to 600 ng/L in reclaimed water with mean value of 352
      ng/L, respectively. The PAH profiles were dominated by low molecular weight PAHs
      (two- and three-ring components) in reclaimed water samples and surface water
      samples. These indicated that PAHs in reclaimed water and surface water might
      origin from oil or sewage contamination (petrogenic input). To elucidate sources,
      molecular indices based on indices among phenanthrene versus anthracene and
      fluoranthene versus pyrene were used to evaluate the possible source (pyrogenic
      and petrogenic sources, respectively) of PAH contamination in reclaimed water and
      surface water. The collected data showed that petrogenic input was predominant at
      almost all the stations investigated. To discriminate pattern differences and
      similarities among samples, principal component analysis (PCA) was performed
      using a correlation matrix. PCA revealed the latent relationships among all the
      surface water stations investigated and confirmed our analytical results. The
      analysis results of the ratios and PCA in this study showed that the ratios and
      PCA could be applied to the surface water investigation to some extent.

PMID- 15943927
TI  - Commentary on recent proposals for classification of dangerous goods for
      transportation.

PMID- 15943928
TI  - Asbestos reclamation at a disused industrial plant, Bagnoli (Naples, Italy).
AB  - Asbestos reclamation works were carried out at a disused industrial plant
      (157,000 m(2)) in Bagnoli, a high population density area of Naples. The case
      study here presented recommends a new reclamation procedure that is not usually
      provided for by current international standards. To this purpose, a specific
      innovative cleaning machine (Safecar) was built in order to control the
      reclamation procedures also in non-confined areas. An accurate identification was
      planned and worked out of the various types of materials (10,111 t) present
      within the area, and this allowed a thorough mapping of the site to be
      decontaminated. Besides these reclamation activities, which were carried out in
      both confined and open sites, each material was cleaned, collected and
      encapsulated following diversified procedures, according to their
      characteristics. Moreover, the evaluation of airborne asbestos fibre
      concentrations, both within and outside the decontaminated area, assured a strict
      respect of environmental safety level.

PMID- 15943929
TI  - Decolourization of aqueous dye solutions by a novel adsorbent: application of
      statistical designs and surface plots for the optimization and regression
      analysis.
AB  - Adsorption of Neolan Blue 2G (Acid Blue 158) and Basic Methylene Blue (Basic Blue
      9) was investigated using a hybrid adsorbent that was prepared by pyrolysing a
      mixture of carbon and flyash at 1:1 ratio. A 2(4) full factorial central
      composite design with nine replicates at the center point and thus a total of 31
      experiments were successfully employed for batch experimental design and analysis
      of the results. The combined effect of pH, temperature, particle size and time on
      the dye adsorption was studied. An empirical model was developed and validated
      applying ANOVA analysis incorporating interaction effects of all parameters and
      optimized using response surface methodology. The optimum pH, temperature,
      particle size and time were found to be 2.20, 27.85 degrees C, 0.0565 mm, 245
      min, respectively, for Acid Blue 158 and those for Basic Blue 9 were 13.40, 28.45
      degrees C, 0.0555 mm and 230 min, respectively. Complete removal (100%) was
      observed for both the dyes using the hybrid adsorbent.

PMID- 15943930
TI  - Copper leaching from a sandy soil: mechanism and parameters affecting EDTA
      extraction.
AB  - A series of 24h batch tests of copper extraction from a sandy soil were performed
      by washing the soil with aqueous solution of ethylenediaminetetraacetic acid,
      EDTA. EDTA versus copper molar ratio were in the range between 1 (equimolar
      tests) and 13.3. The tests were performed at three selected liquid/solid ratio,
      5, 12.5 and 25. Results show that decreasing the pH of the washing solution an
      higher copper extraction yield was achieved: an almost complete copper extraction
      was achieved after 23 h of mixing at a L/S = 5, and after 5 h of mixing at an L/S
      = 12.5. The mechanism of copper extraction was found to involve two sequential
      processes: the former dissolution of metal salts, that lead to an initial high
      concentration of both copper and some competitive cations (essentially Ca(2+)),
      and the following EDTA exchange reaction between calcium and copper complexes,
      which corresponded an increase of pH in the washing solution. A negligible
      extraction of Fe(3+) was also observed at the investigated operative conditions.

PMID- 15943931
TI  - Electrokinetic removal of caesium from kaolin.
AB  - Soil, in the form of kaolin and a sample of natural soil from an industrial site,
      was artificially contaminated with caesium and subjected to electrokinetic
      treatment. The effect of catholyte pH control on the process was investigated
      using different acids to control the catholyte pH. During treatment the in situ
      pH distribution, the current flow, and the potential distribution were monitored.
      At the end of the treatment the pore fluid conductivity and the caesium
      concentration distribution was measured. The results of these experiments showed
      that for caesium contamination, catholyte pH control is essential in order to
      create a suitable environment throughout the soil to enable contaminant removal.
      It was found that the type of acid used to control the catholyte pH affected the
      rate of caesium removal (nitric, sulphuric, acetic and citric acids were tested).
      All of the acids tested were effective, but the highest caesium extraction was
      achieved when nitric acid was used to control the catholyte pH. The relatively
      high adsorption capacity of the soil for caesium was found to significantly
      reduce the rate of removal. After 240 h of treatment at 1 Vcm(-1) (using
      sulphuric acid to control the catholyte pH), less than 80% of the caesium was
      removed from a 30 cm long sample of kaolin. Electrokinetic treatment of the
      industrial soil sample was slower than for the kaolin, but a significant
      extraction rate for caesium was achieved.

PMID- 15943932
TI  - Electrodialytic removal of heavy metals from municipal solid waste incineration
      fly ash using ammonium citrate as assisting agent.
AB  - Electrodialytic remediation, an electrochemically assisted separation method, has
      previously shown potential for removal of heavy metals from municipal solid waste
      incineration (MSWI) fly ashes. In this work electrodialytic remediation of MSWI
      fly ash using ammonium citrate as assisting agent was studied, and the results
      were compared with traditional batch extraction experiments. The application of
      electric current was found to increase the heavy metal release significantly
      compared to batch extraction experiments at comparable conditions (same liquid-to
      solid ratio, same assisting agent, and same extraction time). Up to 86% Cd, 20%
      Pb, 62% Zn, 81% Cu and 44% Cr was removed from 75 g of MSWI fly ash in
      electrodialytic remediation experiments using ammonium citrate as assisting
      agent. The time range for the experiments varied between 5 and 70 days.

PMID- 15943933
TI  - Thermolysis of some transition metal nitrate complexes with 1,4-diamino butane
      ligand.
AB  - Four complexes are prepared and characterized having molecular formula
      [Zn(dab)(2)](NO(3))(2), [Cu(dab)(2)](NO(3))(2).H(2)O,
      [Ni(dab)(2)](NO(3))(2).2H(2)O and [Mn(dab)(2)](NO(3))(2), where dab: 1,4
      diaminobutane. Thermolyses of these complexes were investigated by simultaneous
      thermogravimetry (TG), derivatives thermogravimetry (DTG), differential thermal
      analysis (DTA) and differential scanning calorimetry (DSC). The kinetics of the
      thermolysis at early stages is investigated using isothermal TG by applying model
      fitting and isoconversional method. Thermolytic process is slow in inert (N(2))
      and is fast in air atmosphere due to oxidative nature. To investigate the
      response of these complexes under the condition of rapid heating, ignition delay
      (D(i)) has been measured. Thermal stability of the complexes was found to
      increase in the order Mn < Cu < Ni < Zn.

PMID- 15943934
TI  - Effect of experimentally induced reducing conditions on the mobility of arsenic
      from a mining soil.
AB  - A method for estimating the release of contaminants from contaminated sites under
      reducing conditions is proposed. The ability of two chemical reducing agents,
      sodium ascorbate and sodium borohydride, to produce different redox environments
      in a gold mining soil contaminated with arsenic was investigated. Liquid-solid
      partitioning experiments were carried out in the presence of each of the reducing
      agents at different pH conditions. Both the effect of varying concentrations of
      the reducing agent and the effect of varying pH in the presence of a constant
      concentration of the reducing agent were studied. Concentrations of sodium
      ascorbate ranging from 0.0075 to 0.046 mol L(-1) and concentrations of sodium
      borohydride ranging from 0.0075 to 0.075 mol L(-1) were examined. The addition of
      varying concentrations of sodium borohydride provided greater reducing conditions
      (ranging from -500 to +140 mV versus NHE) than that obtained using sodium
      ascorbate (ranging from -7 to +345 mV versus NHE). The solubilization of arsenic
      and iron was significantly increased by the addition of sodium ascorbate for all
      concentrations examined and pH tested, compared to that obtained under oxidizing
      conditions (as much as three orders of magnitude and four orders of magnitude,
      respectively, for the addition of 0.046 mol L(-1) of sodium ascorbate). In
      contrast, the alkaline and highly reduced soil conditions obtained with sodium
      borohydride lead to a lower effect on arsenic solubilization (as much as one
      order of magnitude for pH values between ca. 7 and 10 and no effect for pH values
      between ca. 10 and 12) and no effect on iron solubilization for all
      concentrations examined and pH tested. At similar ORP-pH conditions the results
      of extraction for arsenic and iron were different for the two reagents used.

PMID- 15943935
TI  - Vitrified metal finishing wastes II. Thermal and structural characterisation.
AB  - Waste filter cakes from two metal finishing operations were heat treated and
      vitrified. Substantial weight loss during heating was due to emission of water,
      volatile sulphur-rich and chlorine-rich compounds, and the combustion of
      carbonaceous components. Estimations of CO(x), SO(x) and HCl emissions were based
      on chemical analyses. Upon cooling from molten, one sample remained amorphous but
      all others partially crystallised. Crystalline nature was dependent upon waste
      composition and the level of P(2)O(5) addition. Thermal stabilities of the waste
      forms were good, but less so than MW, a borosilicate glass developed for its high
      temperature stability. Mossbauer and FTIR analyses showed that iron environments
      in the different vitrified waste forms were very similar. Iron was present
      predominantly as Fe(3+), although the exact redox ratio varied slightly between
      waste forms. Iron in both redox states occupied distorted octahedral coordination
      polyhedra with similar levels of site distortion. Phosphate networks in the
      vitreous materials were highly de-polymerised, consisting largely of (PO(4))(3-)
      monomer and (P(2)O(7))(2-) dimer units. This explained the high chemical
      durability of these waste forms and their structural insensitivity to
      compositional change, underlining their suitability as hosts for the
      immobilisation of toxic and nuclear wastes.

PMID- 15943936
TI  - Stabilization/solidification of galvanic sludges by asphalt emulsions.
AB  - A combination of two-aqueous asphalt emulsions was proposed for
      stabilization/solidification treatment of galvanic sludges prior to landfilling.
      The presented procedure comprises mixing the galvanic sludge with a slow setting
      nonionic asphalt emulsion and subsequently forming a secondary asphalt barrier by
      means of a rapid setting anionic asphalt emulsion. The method was tested on four
      samples of galvanic sludge from various galvanizing plants, with various water
      and pollutant contents. Stabilization efficiency was assessed by water-leaching
      test, TCLP test and by determining ecotoxicity of leachates. Leachate parameters
      exhibited very low values and favorable results of ecotoxicological tests
      indicate high efficiency of the developed procedure for galvanic sludge disposal.

PMID- 15943937
TI  - Adsorption of phthalic acid and its esters onto high-area activated carbon-cloth
      studied by in situ UV-spectroscopy.
AB  - The adsorption behavior of phthalic acid and its three esters dimethyl phthalate,
      diethyl phthalate and diallyl phthalate onto high-area activated carbon-cloth was
      studied by in situ UV-spectroscopic technique. The effect of ionization of
      phthalic acid on its adsorption was examined by carrying out the adsorption
      process in three media; water, 1 M H(2)SO(4) and 0.005 M NaOH. Maximum adsorption
      was observed in 1 M H(2)SO(4) and almost no adsorption in 0.005 M NaOH. These
      results were discussed in terms of electrostatic and dispersion interactions
      between the adsorbate species and the carbon-cloth surface taking the point of
      zero charge (pH(pzc)) of the carbon-cloth into account. The adsorption process
      for the phthalate species studied was found to follow the first-order rate law,
      and the rate constants were determined. The isotherm data for the adsorption of
      phthalic acid and its esters were derived experimentally and fitted to Langmuir
      and Freundlich isotherm equations. Both equations were found to represent the
      experimental isotherm data almost equally well.

PMID- 15943938
TI  - Removal of arsenic and humic substances (HSs) by electro-ultrafiltration (EUF).
AB  - A laboratory scale electro-ultrafiltration (EUF) system was developed and used to
      explore the removal of arsenic and humic substances (HSs) from water. As a
      negatively charged species, arsenate(V) was readily removed after applying
      voltage to the EUF cell. Arsenite(III) was removed via EUF after the pH of the
      water had been adjusted. Meanwhile, the rejection of HSs increased due to the
      presence of an electric field. This study also showed that the removal of
      arsenite(III) from water relies primarily on electrostatic and non-electrostatic
      mechanisms. In the presence of HSs, arsenate(V) complexed with the HSs and was
      then able to be removed by EUF. This study demonstrates that EUF is a highly
      promising means of removing arsenic from water.

PMID- 15943939
TI  - Buprenorphine versus methadone in the treatment of pregnant opioid-dependent
      patients: effects on the neonatal abstinence syndrome.
AB  - This study was designed to compare the neonatal abstinence syndrome (NAS) in
      neonates of methadone and buprenorphine maintained pregnant opioid-dependent
      women and to provide preliminary safety and efficacy data for a larger multi
      center trial. This randomized, double-blind, double-dummy, flexible dosing,
      parallel-group controlled trial was conducted in a comprehensive drug-treatment
      facility that included residential and ambulatory care. Participants were opioid
      dependent pregnant women and their neonates. Treatment involved daily
      administration of either sublingual buprenorphine or oral methadone using
      flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary a priori outcome
      measures were: (1) number of neonates treated for NAS; (2) amount of opioid
      agonist medication used to treat NAS; (3) length of neonatal hospitalization; and
      (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%)
      methadone-exposed neonates were treated for NAS (p=.23). Total amount of opioid
      agonist medication administered to treat NAS in methadone-exposed neonates was
      three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6;
      p=.13). Length of hospitalization was shorter for buprenorphine-exposed than for
      methadone-exposed neonates (p=.021). Peak NAS total scores did not significantly
      differ between groups (p=.25). Results suggest that buprenorphine is not inferior
      to methadone on outcome measures assessing NAS and maternal and neonatal safety
      when administered starting in the second trimester of pregnancy.

PMID- 15943940
TI  - Who becomes cannabis dependent soon after onset of use? Epidemiological evidence
      from the United States: 2000-2001.
AB  - In this paper we estimate the risk of becoming cannabis dependent within 24
      months after first use of cannabis and examine subgroup variation in this risk.
      The study estimates are based on the National Household Survey on Drug Abuse
      conducted during 2000-2001, with a representative sample of U.S. residents ages
      12 and older (n=114,241). A total of 3352 respondents were found to have used
      cannabis for the first time within a span of up to 24 months prior to assessment.
      An estimated 3.9% of these recent-onset users developed a cannabis dependence
      syndrome during the interval since first use (median interval duration
      approximately 12 months). Excess risk of cannabis dependence was found for those
      with cannabis onset before late-adolescence, those with family income less than
      US dollars 20,000, and those who had used three or more drugs before the first
      use of cannabis (i.e., tobacco, alcohol, and other drugs). While these findings
      generally support previous study results, this study's focus on recent-onset
      users more closely approximates prospective and longitudinal research on the
      incidence (risk) of becoming cannabis dependent soon after onset of cannabis use,
      removing the influence of users with long-sustained or persistent cannabis
      dependence developed years ago.

PMID- 15943941
TI  - Prevalence and correlates of cocaine physical dependence subtypes using the DSM
      IV in outpatients receiving opioid agonist medication.
AB  - The present study used a cross-sectional design to examine the relationship
      between endorsement of physiological dependence to cocaine (i.e., tolerance
      and/or withdrawal) and lifetime, and current problem severity (i.e., psychiatric
      and substance use disorders, medical and psychosocial problems) for opioid and
      cocaine dependent individuals (n=719) newly admitted to a treatment program using
      opioid-agonist medication. All participants completed the structured clinical
      interview for the Diagnostic and Statistical Manual (DSM-IV) (SCID-IV) and the
      Addiction Severity Index (ASI). Participants were first classified into
      physiological (n=549) versus non-physiological (n=170) cocaine dependence groups
      for one set of analyses and then categorized into one of four groups for further
      analyses: (1) tolerance only (n=215), (2) tolerance plus withdrawal (n=279), (3)
      withdrawal only (n=55) or (4) no physiological dependence (n=170). Those
      participants who endorsed physiological dependence reported higher rates of
      lifetime psychiatric and substance use disorders, higher rates of current drug
      use and more current problems. The four-group analyses showed that endorsement of
      withdrawal, with or without tolerance, was associated with the most severe
      problems. These findings suggest that physiological dependence to cocaine
      (particularly the presence of withdrawal) is a marker for a more severe substance
      use disorder and higher rates of comorbid psychopathology and other problems.

PMID- 15943942
TI  - Validation of the timeline follow-back in the assessment of adolescent smoking.
AB  - The timeline follow-back instrument (TLFB) is a valid and reliable method of
      quantifying alcohol use patterns. The use of this instrument has been expanded to
      assess other behaviors, such as drug use, sexual behavior, binge eating, and
      panic attacks. Some evidence for the validity and reliability of this assessment
      instrument has emerged in the area of adult smoking. However, to date, there is
      no published evidence of its reliability and validity in the assessment of
      adolescent smoking. The purpose of this study is to present early evidence of the
      utility of the TLFB to collect information on adolescent smoking behavior.
      Through secondary data analysis of four studies on adolescent smokers, we
      examined the associations between the TLFB and measures of dependence, smoking
      history, respiratory symptoms, and saliva cotinine. Moreover, we examined the
      stability of the TLFB data across two 15-day time periods. Results provide
      preliminary evidence of the validity and reliability of the TLFB in the
      assessment of adolescent smoking. In particular, the TLFB instrument offered
      important data on the heterogeneity of adolescent smoking patterns beyond a
      global measure of cigarettes per day, and the reduction of digit bias.
      Implications of these findings for the assessment of adolescent smoking are
      discussed.

PMID- 15943943
TI  - Validation of the nicotine dependence syndrome scale (NDSS): a criterion-group
      design contrasting chippers and regular smokers.
AB  - The nicotine dependence syndrome scale (NDSS) is a new multi-dimensional measure
      of nicotine dependence, yielding five scores for different aspects of dependence
      as well as a total score. In this study, we tested the NDSS in a young adult
      sample (mean age=24), using an extreme-groups comparison between non-dependent
      smokers (chippers, n=123) and regular smokers (n=130). Scores on each NDSS
      subscale strongly discriminated between the groups, with the NDSS-total
      discriminating them almost perfectly. The subscales were generally independent
      discriminators, demonstrating the discriminant validity of the subscales. NDSS
      scales also discriminated levels of intake and dependence within the chippers
      group, suggesting that the scales were sensitive to individual differences even
      at the very low end of the dependence continuum.

PMID- 15943944
TI  - Correlates of nonmedical use of prescription benzodiazepine anxiolytics: results
      from a national survey of U.S. college students.
AB  - This study examined the prevalence and correlates associated with the nonmedical
      use of prescription benzodiazepine anxiolytics among U.S. college students. This
      study analyzed data from a nationally representative sample of 10,904 randomly
      selected students attending 119, 4-year U.S. colleges in 2001. The lifetime
      prevalence of nonmedical prescription benzodiazepine anxiolytic use was 7.8%,
      past year prevalence was 4.5% and past month was 1.6%. Past year rates of
      nonmedical use of prescription anxiolytics ranged from zero percent at the lowest
      use schools to 20% at the highest use school. Multivariate regression analyses
      indicated nonmedical use was more likely to occur among college students who were
      White, had both male and female sex partners and reported higher rates of
      substance use and other risky behaviors. In addition, nonmedical use of
      prescription benzodiazepine anxiolytics was less likely to occur among college
      students who attended college in the North Central region of the U.S. or
      historically black colleges and universities (HBCUs). This study provides
      evidence that the nonmedical use of prescription benzodiazepine anxiolytics
      represents a problem on some college campuses and among certain subgroups of U.S.
      college students. These findings have important implications for developing
      prevention efforts aimed at reducing the nonmedical use of prescription
      benzodiazepine anxiolytics among college students while not hindering the
      effective clinical treatment for various anxiety disorders.

PMID- 15943945
TI  - Alterations of the vascular basal lamina in the cerebral cortex in drug abuse: a
      combined morphometric and immunohistochemical investigation.
AB  - In drug abusers, white matter hyperintensities, perfusion deficits, and metabolic
      disturbances are detected by neuroimaging analyses in different brain regions. A
      specific pattern of involvement or a predominance of a specific brain region
      cannot be drawn. To examine changes of the cerebral microvasculature as a
      possible morphological substrate of the neuroimaging findings, brain specimens of
      12 polydrug abusers and 8 controls were obtained at autopsy. The basal lamina of
      blood vessels from the frontal, temporal, parietal, and occipital lobes was
      analysed by means of immunohistochemistry for collagen type IV. The numerical
      density of vessels was determined in the gray and white matter, and their
      staining intensity was rated using a three-point scale. In the gray and white
      matter of polydrug abusers, the number of vessels showing strong immunoreactivity
      for collagen type IV was significantly reduced, whereas the number of vessels
      with mild and moderate immunoreactivity was increased as compared to controls.
      The total numerical density of vessels was not significantly changed. Our results
      show a significant reduction in immunoreactivity for collagen type IV in the
      brains from polydrug abusers compared to controls, which may be due to a thinning
      of the basal lamina of cerebral vessels. The data of the present study show
      morphological changes of the basal lamina in the brain of polydrug abusers, which
      might represent the morphological substrate of a disturbed blood-brain barrier.
      However, it remains yet to be established if the observed changes are responsible
      for the alterations seen in different neuroimaging analyses and which drug might
      be of major pathogenetic significance.

PMID- 15943946
TI  - Depression syndromes with risk of alcohol dependence in adulthood: a latent class
      analysis.
AB  - Using prospectively gathered data, we assessed whether depression is associated a
      risk for late-onset alcohol dependence, and whether that relationship differed by
      gender. The baseline interview was completed in 1981 (mean age=41.7 years,
      standard deviation (S.D.)=17.0, range 18-86) on a probability sample of Baltimore
      residents as part of the Epidemiologic Catchment Area Program. Between 1993 and
      1996, the original cohort was traced (73% of the survivors were re-interviewed,
      n=1920). Baseline depression items were subjected to gender-specific latent class
      analyses prior to exploring associations between class membership and two
      classifications of alcohol dependence: (1) lifetime prevalence, and (2) new onset
      assessed at follow-up. A depression syndrome class was identified (24% of the
      females and 20% of the males). The odds of lifetime alcohol dependence among
      those in the depressive syndrome class was significantly elevated for both sexes,
      relative to the non-depressed class. However, no appreciable association was
      found for depressive syndrome with the development of alcohol dependence. In this
      sample of middle-aged adults, the evidence supports an association for the
      presence of a depressive syndrome with lifetime alcohol dependence, but not for
      the new onset of alcohol dependence. Other predictors of alcohol dependence
      identified in the analyses are discussed.

PMID- 15943947
TI  - The level of response to alcohol in daughters of alcoholics and controls.
AB  - BACKGROUND: The low level of response (LR) to alcohol is a genetically influenced
      characteristic related to the development of alcohol use disorders (AUDs). This
      phenotype is found in men with a family history (FH) of alcoholism, predicts
      future AUDs, and has heritabilities as high as 60%. However, despite evidence of
      genetic influences for AUDs in both sexes, the majority of studies evaluating
      differences in LR across high- and low-risk groups have been conducted on males,
      and it is unclear how generalizable these results are to women. METHODS: Twenty
      five women who are family history positive (FHP) for alcohol dependence were
      matched with 25 women with no FH of alcoholism (FHN) on factors that may impact
      LR. Using an alcohol challenge paradigm, data on the reaction to a moderate dose
      of alcohol were gathered over a period of 3.5 h. Assessments included breath
      alcohol concentrations (BrACs), the Subjective High Assessment Scale (SHAS), as
      well as body sway or static ataxia. RESULTS: Family history positives reported
      lower subjective intoxication than FHNs. In addition, when body sway scores were
      corrected for skewness, FHPs had significantly lower scores on alcohol-related
      changes in lateral sway. These differences remained after considering the effects
      of drinking history and BrAC values. CONCLUSIONS: This study evaluated the LR to
      alcohol in the largest sample of alcohol challenges in matched FHP and FHN women
      to date. Overall, the findings are consistent with most data from earlier
      investigations of smaller sized samples of FHP women. The results suggest that,
      similar to sons of alcoholics, a low LR to alcohol might also be characteristic
      of daughters of alcoholics.

PMID- 15943948
TI  - The effect of buprenorphine and benzodiazepines on respiration in the rat.
AB  - Methadone and buprenorphine are the two main opioid substitution treatments for
      heroin dependence currently offered in Australia. A number of publications have
      implicated buprenorphine as being potentially dangerous in combination with
      benzodiazepines but no comparison has been made to the relative dangers of
      benzodiazepines combined with buprenorphine or methadone. The effect of i.v.
      methadone and buprenorphine on respiration was investigated by evaluating
      arterial blood pCO2, pO2 and pH, and measuring respiratory rate in rats.
      Measurements were taken at 0, 15, 30, 60, 120, 180 and 240 min after i.v.
      administration of methadone or buprenorphine. Effects on respiration were
      greatest 15 min after i.v. drug administration. The effect of methadone and
      buprenorphine on respiration was compared with and without diazepam pretreatment
      (20 mg/kg). Buprenorphine alone exhibited a bell shaped dose response inhibition
      of respiration; however the plateau of the dose response inhibition on
      respiration was lost when administered in combination with diazepam. Methadone
      showed a dose-dependent inhibitory effect on respiration, which was potentiated
      with diazepam pretreatment. While the effect of diazepam pretreatment was the
      abolishment of the protective bell shaped dose response effect on respiration,
      the effect of buprenorphine and diazepam was not greater than methadone and
      diazepam.

PMID- 15943950
TI  - The practice of office-based buprenorphine treatment of opioid dependence: is it
      associated with new patients entering into treatment?
AB  - Office-based buprenorphine holds the promise of bringing patients who have never
      received pharmacotherapy into treatment. In a cross-sectional and longitudinal
      analysis, we compared patients entering a clinical trial of buprenorphine in a
      Primary Care Clinic (PCC) and those entering a local Opioid Treatment Program
      (OTP) and we compared the clinical characteristics and treatment outcomes of PCC
      patients with no history of methadone treatment (new-to-treatment) to those with
      prior methadone treatment. PCC subjects (N=96) were enrolled in a 26-week
      randomized clinical trial of office-based buprenorphine/naloxone provided in a
      PCC. OTP subjects (N=94) were enrolled in methadone maintenance during the same
      time period. PCC subjects compared with OTP subjects were more likely to be male
      (77% versus 55%, p<0.01), full-time employed (46% versus 15%, p<0.001), have no
      history of methadone treatment (46% versus 61%, p<0.05), have fewer years of
      opioid dependence (10 versus 15, p<0.001), and lower rates of injection drug use
      (IDU) (44% versus 60%, p=0.03). The new-to-treatment PCC subjects were younger
      (36 years versus 41 years, p=0.001), more likely to be white (77% versus 57%,
      p=0.04), had fewer years of opioid dependence (7 versus 14, p<0.001), were less
      likely to have a history of IDU (35% versus 54%, p=0.07), and had lower rates of
      hepatitis C (25% versus 61%, p=0.002) than subjects with prior methadone
      treatment. Abstinence and treatment retention were comparable in both groups. The
      results suggest that office-based treatment of opioid dependence is associated
      with new types of patients entering into treatment. Treatment outcomes with
      buprenorphine in a PCC do not vary based on history of prior methadone treatment.

PMID- 15943949
TI  - Alcohol intoxication and sexual risk behaviors among rural-to-urban migrants in
      China.
AB  - BACKGROUND: The migrant population in China is at high risk for sexual risk
      behavior and alcohol intoxication. Information about the prevalence of alcohol
      intoxication and its association with sexual risk behavior among migrants is
      needed for designing effective intervention prevention programs for reduction in
      alcohol abuse and HIV infection. METHODS: Cross-sectional data were collected
      from 2153 sexually experienced young rural-to-urban migrants in Beijing and
      Nanjing, China, in 2002. RESULTS: Approximately one-third of the participants had
      been intoxicated with alcohol at least once during the previous month, with more
      males than females reporting intoxication (40.2% versus 23.7%, p<0.001). Compared
      to non-intoxicated participants, respondents with alcohol intoxication in
      previous 30 days reported more psychological problems, including higher
      depression scores, lower levels of satisfaction with life and work, and higher
      perception of peer involvement in risk behavior. Intoxicated respondents were
      more likely to engage in premarital sex than non-intoxicated respondents (76%
      versus 60.2%, p<0.001), have multiple sexual partners (13.4% versus 5.2%,
      p<0.001), purchase sex (12.6% versus 4.9%, p<0.001), and sell sex (10.1% versus
      3.7%, p<0.001). However, there was no association between alcohol intoxication
      and inconsistent/non-use of condoms. Multivariate analysis controlling for
      depression, peer risk involvement, age, gender, and other socio-demographic
      variables indicated that alcohol intoxication was independently correlated with
      premarital sex, multiple sexual partners, and buying and selling sex.
      CONCLUSIONS: Compared to the general Chinese population, levels of intoxication
      were elevated among Chinese rural-to-urban migrants. Alcohol intoxication was
      associated with sexual risk behaviors. HIV/AIDS prevention and intervention
      efforts should include components of alcohol use/abuse prevention for an
      effective reduction of sexual risk among young rural-to-urban migrants in China.

PMID- 15943951
TI  - Expression of the GLUT1 and GLUT9 facilitative glucose transporters in embryonic
      chondroblasts and mature chondrocytes in ovine articular cartilage.
AB  - Glucose transport across the chondrocyte membrane is essential for chondrogenesis
      and the development of the skeletal system. We have previously used RT-PCR to
      show that fully developed human articular chondrocytes express transcripts for
      the GLUT1 and GLUT9 glucose transporters. In this study we report on the
      expression and immunohistochemical localization of the GLUT1 and GLUT9 proteins
      in embryonic and mature ovine cartilage. We also provide Western blot evidence
      for GLUT1 and GLUT9 expression in mature ovine chondrocytes. Ovine embryos
      (developmental stages E32 to E36 and E42 to E45) were obtained from pregnant ewes
      humanely killed by injection with sodium pentobarbitone. Embryos were fixed and
      processed for immunohistochemistry. Polyclonal antibodies to GLUT1 and GLUT9
      revealed that both transporters are expressed in developing chondrocytes in ovine
      embryos and in the superficial, middle and deep layers of ovine cartilage from
      mature animals. GLUT1 expression was observed in erythrocytes and organs
      including heart, liver, and kidney. GLUT9 was also found in heart, kidney and
      liver. Western blotting confirmed the presence of the GLUT1 protein which
      migrated between the 50 and 64 kDa markers and two specific GLUT9 bands migrating
      under the 50 and 60 kDa markers, respectively. The presence of GLUT1 and GLUT9 in
      developing joints of ovine embryos suggests that these proteins may be important
      in glucose delivery to developing chondroblasts. Expression of these GLUT
      isoforms may be an important bioenergetic adaptation for chondrocytes in the
      extracellular matrix of developing cartilage.

PMID- 15943953
TI  - Formation of division spindles in higher plant meiosis.
AB  - Depolymerisation of the MT cytoskeleton during late prophase makes it impossible
      to follow the cytoskeleton cycle in centrosomeless plant meiocytes. This paper
      describes rearrangements of the MT cytoskeleton during plant meiotic spindle
      formation in normally dividing pollen mother cells in various higher plant
      species and forms in which the cytoskeleton does not depolymerise at prophase. In
      such variants of the wild-type, cytoskeleton rearrangements can be observed at
      late prophase/early prometaphase. Radial MT bundles coalesce in the meridian
      plane, reorientate tangentially, curve and give rise to a developed ring-shaped
      perinuclear cytoskeleton system at the meridian. During nuclear envelope
      breakdown this ring disintegrates and splits into a set of free MT bundles. Three
      sub-stages of prometaphase are indicated: early prometaphase (disintegration of
      perinuclear ring and invasion of MTs into the former nuclear area), middle
      prometaphase or chaotic stage (formation of bipolar spindle fibres), and late
      prometaphase (formation of bipolar spindle). Analysis of a range of abnormal
      phenotypes (disintegrated, multiple, polyarchal, chaotic spindles) reveals two
      previously unknown processes during late prometaphase: axial orientation and
      consolidation of the spindle fibres.

PMID- 15943952
TI  - Temporal changes in the expression of protein phosphatase 1 and protein
      phosphatase 2A in proliferating and differentiating murine erythroleukaemia
      cells.
AB  - Rhythmic changes in the expression of protein phosphatase 1 (PP1) and protein
      phosphatase 2A (PP2A) were investigated during hexamethylene bisacetamide (HMBA)
      induced differentiation of murine erythroleukaemic (MEL) cells. Cell extracts
      were analysed by SDS-PAGE and western immunoblotting using specific antibodies.
      An immunospecific band of molecular mass 36 kDa (catalytic subunit) was detected
      for PP1. For PP2A, two immunospecific bands of 32 kDa (proteolytically cleaved
      catalytic subunit) and 36 kDa (catalytic subunit) were observed. Comparisons of
      proliferating and differentiating cells using only one time point showed no
      significant differences between mean values for the expression of the PP1 or PP2A
      enzyme proteins. This kind of analysis, implying that HMBA had little effect,
      proved misleading, as comparisons using multiple time points showed rhythmic
      patterns of protein expression which were modulated by the differentiating agent.
      The effects were complex affecting both the frequency and phasing of rhythms. The
      results add further support for the view that live cells are multi-oscillators
      and for the concept that differentiation depends on changes in temporal
      organization of complex autodynamic feedback loops and multiple interactions
      between control circuits performing in parallel. In particular, modulation of the
      dynamics of key proteins, such as PP1 and PP2A, may be a possible mechanism for
      controlling cellular function and reversing transformation in accordance with
      long standing theoretical and other experimental data.

PMID- 15943954
TI  - Elevated expression of NF-kappaB and Bcl-2 proteins in C2C12 myocytes during
      myogenesis is affected by PD98059, LY294002 and SB203580.
AB  - The initial phase of muscle differentiation depends on the activities of protein
      kinases including phosphatidylinositol-3 kinase (PI-3K), the extracellular signal
      regulated kinases ERK1/2 (p42 and p44), and p38 kinase. Myogenesis is also
      characterized by an apoptosis-resistant phenotype of myotubes. The effects of
      inhibitors of the above-mentioned protein kinases on myogenesis from C2C12 mouse
      myoblasts and on muscle cell apoptosis were examined individually over 5
      successive days. The negative effects of PD98059 (5, 25, 50 microM), LY294002 (1,
      5, 10 microM) and SB203580 (1, 5, 10 microM) on cell viability were evident at
      the initial stage of myogenesis (up to the 3rd day). On the 3rd day, nuclear
      expression of myogenin was suppressed dose-dependently by SB203580. In contrast,
      decreased cytoplasmic levels but elevated nuclear expressions of myogenin were
      observed in myotubes treated with PD98059 or LY294002. SB203580 treatment
      confirmed that p38 kinase is involved in the onset of myogenesis. The cytoplasmic
      and nuclear expression of NF-kappaB was elevated after treatment with the above
      mentioned protein kinase inhibitors. Likewise, Bcl-2 expression in the cytosol
      increased. These studies might shed more light on the role of selected kinases
      and some survival systems in myogenesis impaired by neuromuscular disorders as
      well as safety of the treatment of the proliferative diseases with the kinase
      inhibitors.

PMID- 15943955
TI  - Establishing a link between heart rate and pain in healthy subjects: a gender
      effect.
AB  - Heart rate (HR) is currently used by rehabilitation clinicians as a complementary
      objective measure of pain. The premise is that, as pain increases, HR should also
      increase. However, this relationship is not clearly established. The goal of this
      study was to verify the relationship between HR and pain perception. Thirty-nine
      healthy volunteers participated in this experimental study. Painful stimuli were
      induced by a 2-minute immersion of the hand in hot water (47 degrees C). HR was
      recorded before and during the stimulation and was matched to a pain rating. We
      observed a rise of 11% in HR after 2 minutes of immersion. There was a
      significant intrasubject correlation between HR and pain intensity (r = 0.50, P <
      .001) and pain unpleasantness (r = 0.55, P < .001). Furthermore, there was a
      strong gender effect in the intersubject correlations. Men presented a strong
      correlation between mean HR and mean pain perception (intensity: r = 0.77,
      unpleasantness: r = 0.86), whereas this relationship was absent in women
      (intensity: r = -0.2, unpleasantness: r = 0.001). In conclusion, results show
      that, for healthy volunteers, experimental pain can elicit a rise in HR up to
      11%. Moreover, the relationship between HR response and pain is gender related.
      Considering that a positive relationship between HR and pain perception was only
      found in men, these results do not support a clinical significance of the use of
      HR for pain evaluation in women. Clinical implications need to be further
      evaluated with patients before clinicians can use HR as a complementary tool in
      pain assessment. PERSPECTIVE: A positive correlation between HR and pain was
      observed for men but not for women. These differences underline the importance of
      taking into account gender differences in the development of complementary pain
      assessment. Further research should be conducted to verify the role of sex
      hormones on heart rate and pain.

PMID- 15943956
TI  - Temporal summation of pain evoked by mechanical stimulation in deep and
      superficial tissue.
AB  - Temporal summation of deep tissue pain has been suggested to be facilitated in
      chronic musculoskeletal pain syndromes. This study aimed to test whether temporal
      summation of mechanical induced pressure pain is (1) more pronounced at short (1
      second) interstimulus intervals (ISIs) compared with long ISI (30 seconds), (2)
      more potent than summation elicited by pure skin stimulation, and (3) attenuated
      in women compared with men. Twelve age-matched men and 12 women were included. A
      computer-controlled pressure stimulator with a probe surface of 1 cm2 was used to
      give 10 stimulations to the tibialis anterior, tibia periosteum, and the first
      web of the hand. Sequential stimulation at pressure pain threshold intensity was
      applied with different ISIs (1, 3, 5, 10, and 30 seconds). The pain intensity was
      assessed on a visual analog scale (VAS) after each individual stimulus. The VAS
      scores after the 10th stimulation with 1-second ISI were increased (P < .05) by
      418% +/- 77%, 378% +/- 89%, and 234% +/- 66% compared with the first stimulation
      for tibia, tibialis anterior, and web, respectively. Temporal summation of pain
      was observed for all ISIs in tibialis anterior and tibia, eg, 30-second ISI
      evoked a VAS increase of 192% +/- 71 % (tibia) and 117% +/- 42% (tibialis
      anterior) compared with the first stimulation. The VAS score after the 10th web
      stimulation was smaller (P < .05) than that of the 10th tibialis anterior or
      tibia stimulation. A regression analysis between stimulation number and VAS score
      showed that the pain intensity increased progressively (1) more for 1-second ISIs
      compared with longer ISIs (P < .01) and (2) faster in deep tissue compared with
      skin (P < .01). No gender difference was observed. The temporal summation might
      be related to both central and peripheral mechanisms. PERSPECTIVE: Pain
      originating in deep tissue influences central pain processing systems more than
      superficial tissue. This might be of importance in patients with musculoskeletal
      pain.

PMID- 15943957
TI  - Pain, medication use, and health-related quality of life in older persons with
      postherpetic neuralgia: results from a population-based survey.
AB  - Persons aged >65 years with pain caused by postherpetic neuralgia (PHN) were
      recruited via advertisements in 24 US newspapers and were mailed a questionnaire
      that addressed pain intensity (average, worst, least, current), pain interference
      (with general activity, mood, relations with other people, sleep, enjoyment of
      life), and health-related quality of life (using the EuroQoL health measure [EQ
      5D] and a global rating scale). Respondents also were asked about their use of
      medication for shingles pain. A total of 385 persons completed the survey; 61%
      were >75 years of age. Mean (+/-standard deviation) duration of PHN was 3.3 (+/
      4.0) years. Only about one half had taken prescription medication for shingles
      pain during the prior week; dosages were typically low. Mean average, worst,
      least, and current pain caused by shingles (0- to 10-point scale) was 4.6 (+/
      2.1), 6.0 (+/-2.4), 2.9 (+/-2.3), and 4.0 (+/-2.7), respectively. Mean pain
      interference with general activity, mood, relations with other people, sleep, and
      enjoyment of life (0- to 10-point scale) was 3.7 (+/-3.1), 4.3 (+/-2.9), 3.0 (+/
      2.8), 3.8 (+/-2.9), and 4.5 (+/-3.1), respectively. The mean EQ-5D health index
      score was 0.61; respondents rated their overall health as 65.7 (+/-21.1) on a 100
      point scale. PHN causes substantial pain, dysfunction, and poor health-related
      quality of life in older persons, many of whom might be suboptimally treated.
      PERSPECTIVE: Many older persons (age >65 years) with PHN experience longstanding,
      severe, and debilitating pain and poor health-related quality of life; levels of
      dissatisfaction with treatment are high. Our study highlights the need for
      improved management of this disease.

PMID- 15943958
TI  - Medication Quantification Scale Version III: update in medication classes and
      revised detriment weights by survey of American Pain Society Physicians.
AB  - The Medication Quantification Scale (MQS) is an instrument with potential
      clinical and research applications for quantifying medication regimen use in
      chronic pain populations. The MQS was developed in 1992 and updated in 1998 (MQS
      II) as a tool to co-quantify 3 relevant aspects of medications prescribed for
      chronic nonmalignant pain: drug class, dosage, and detriment (risk). This 2003
      version (MQS III) is the third iteration of the scale, featuring new detriment
      weights determined by surveying all physician members of the American Pain
      Society in the United States via mail. A total of 248 physicians (18%) responded
      with their opinion as to the detriment of 22 mechanistically distinct medication
      classes. Overall, the physician ratings of detriment weight were relatively
      consistent (alpha = .84). The increased number of survey responses encompassed a
      wide range of disciplines, thus reducing discipline bias and introducing several
      important changes to MQS scoring. Some medication classes previously rated with
      low detriment weights (eg, nonsteroidal anti-inflammatory drugs) increased in
      detriment weight (from 2 to 3.4), whereas other classes previously given high
      weights (eg, "strong" opioids) received lower detriment ratings (from 5 to 3.4)
      in this survey. The MQS III must now be validated in clinical and research
      applications. PERSPECTIVE: The MQS is a tool to objectively quantify pain. It
      computes a single numeric value for a patient's pain medication profile. This
      number can be used by both clinicians and researchers to track pain levels
      through a treatment course or research study.

PMID- 15943959
TI  - Influence of estrous cycle and gonadal hormone depletion on nociception and
      opioid antinociception in female rats of four strains.
AB  - Evidence suggests that gonadal hormones can modulate sensitivity to nociceptive
      stimuli and opioid antinociception. However, cross-study comparisons addressing
      the nature of this modulation have been complicated by a number of methodologic
      factors, including the use of different rodent strains and opioids. The present
      study examined the influence of estrous cycle and gonadal hormone depletion
      (ovariectomy) on thermal nociception and opioid antinociception in female F344,
      Lewis, Long Evans, and Wistar rats. Estrous cycle-dependent differences in
      nociceptive sensitivity were not observed in any of the strains. Ovariectomy
      decreased nociceptive sensitivity relative to their intact female counterparts.
      In normal cycling females, morphine and buprenorphine were generally most potent
      in metestrus and proestrus and least potent in estrus. The magnitude of these
      differences was consistently larger with buprenorphine. Ovariectomy increased the
      antinociceptive potency of morphine and buprenorphine, with this effect also
      being larger with buprenorphine. These data suggest that in adult females of a
      number of rat strains, estrous cycle and gonadal hormone depletion modulate the
      antinociceptive potency of opioids, with the magnitude of this effect being
      dependent on the type of opioid. In contrast, depletion of gonadal hormones, but
      not estrous cycle, modulates thermal nociceptive sensitivity in adult female
      rats. PERSPECTIVE: Gonadal hormones influence opioid antinociception, and this
      effect is apparent across different genetic backgrounds. These results suggest
      that the phase of the menstrual cycle might alter the effectiveness of certain
      opioids administered to relieve pain in women.

PMID- 15943960
TI  - Fear of movement: factor structure of the tampa scale of kinesiophobia in
      patients with fibromyalgia syndrome.
AB  - Chronic pain patients often report fears that movement will exacerbate their
      symptoms. The Tampa Scale of Kinesiophobia (TSK) was designed to assess fear of
      movement. Previous findings with the TSK showed inconsistent factor structures
      and varied measurement properties. The TSK was completed by a sample of 233
      patients with fibromyalgia syndrome who were being evaluated for participation in
      a rehabilitation program. A principal components analysis initially derived a 5
      factor solution. However, the factor structure accounted for less than 50% of the
      variance, and the internal consistency of the factors was below conventional
      standards (<0.70). A series of principal components analyses "forcing" different
      factor structures revealed that the best solution was a single factor solution
      that contained 4 of the original 17 TSK items, accounting for more than 50% of
      the variance with adequate internal consistency (alpha =0.71). Inspection of the
      content of these 4 items, however, suggests that this factor more likely
      represents catastrophic thinking, rather than fear of movement. Nevertheless, for
      patients with fibromyalgia syndrome, a 4-item TSK appears to retain the most
      acceptable factor solution while also maintaining adequate internal consistency.
      PERSPECTIVE: Although the TSK is one of the most commonly used measures of fear
      of movement, the present study using the TSK with a sample of patients with
      fibromyalgia syndrome suggests that the measurement properties of the TSK are
      problematic. Recommendations for use of the TSK are provided.

PMID- 15943961
TI  - Adding ultralow-dose naltrexone to oxycodone enhances and prolongs analgesia: a
      randomized, controlled trial of Oxytrex.
AB  - Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone, an
      opioid antagonist. Ultralow-dose opioid antagonists have been demonstrated to
      enhance and prolong opiate analgesia and alleviate opioid tolerance and
      withdrawal in rodents. This 3-week, Phase II clinical trial assessed safety and
      analgesic efficacy of Oxytrex in patients with moderate to severe pain from
      osteoarthritis. Patients with a pain score > or =5 received placebo, oxycodone 4
      times a day (qid), Oxytrex qid, or Oxytrex twice a day (bid). All active
      treatment groups received the same total daily dose and dose escalation of
      oxycodone starting at 10 and ending at 40 mg/day. Importantly, the Oxytrex bid
      group received a lower daily dose of naltrexone than Oxytrex qid (0.002 vs 0.004
      mg/day). Oxytrex bid produced a 39% reduction in pain intensity, which was
      significantly greater than that of placebo (P < .001), oxycodone qid (P = .006),
      and Oxytrex qid (P = .003). Oxytrex bid was also superior to placebo in quality
      of analgesia (P = .002), duration of pain control each day (P = .05), patients'
      global assessments (P = .04), and the Western Ontario and MacMaster Universities
      Osteoarthritis Index total score (P = .03). The incidence of side effects was
      comparable between active treatments. In this Phase II dose-ranging study,
      Oxytrex bid demonstrated greater pain relief with a more convenient dosing
      schedule compared to oxycodone qid. PERSPECTIVE: Preclinical data have shown
      ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while
      reducing analgesic tolerance and physical dependence. Recent molecular
      pharmacology data show a mechanism of action to be the prevention of aberrant G
      protein coupling by opioid receptors that underlies opioid tolerance and
      dependence.

PMID- 15943962
TI  - The meaning of pain relief in a clinical trial.
AB  - Data from 207 subjects in the early postoperative period in a controlled clinical
      trial were used to examine the factors that contribute to global ratings of
      satisfaction with pain relief. Prerecovery to postrecovery period change scores
      in pain intensity were not significantly associated with level of satisfaction
      with pain relief. However, endpoint pain intensity, average pain intensity,
      recall rating of maximum pain, and actual maximum pain during the immediate
      postoperative period all predicted relief satisfaction. Of these predictors,
      average pain and change in pain were associated with relief satisfaction when
      controlling for all the predictors. The average pain levels reported by patients
      who rated themselves as being "very satisfied" and "somewhat satisfied" with the
      level of pain relief were 32.86 (on a 0 to 100 visual analogue scale [VAS]) and
      40.00, respectively. Patients who were "slightly satisfied," "neither satisfied
      nor dissatisfied," and "slightly," "somewhat," and "very dissatisfied" reported
      similar levels of average pain during the recovery period (range = 51.37-56.32).
      The findings indicate that the primary variable related to relief satisfaction
      following surgery during the immediate postoperative period is an average of the
      pain intensity experienced during this time period. PERSPECTIVE: In order to be
      "very satisfied" with pain relief during the postoperative period, patients are
      not required to experience no pain. Rather, the study findings suggest that mild
      pain averaging less than 40 on a 0 to 100 VAS is adequate. However, moderate pain
      during the early recovery period averaging about 50 or more on a 0 to 100 VAS
      appears to be associated with dissatisfaction with pain relief.

PMID- 15943963
TI  - In search of pain.

PMID- 15943964
TI  - A crevice adjoining the ribosome tunnel: hints for cotranslational folding.
AB  - RNA protection experiments and the crystal structure of a complex of the large
      ribosomal subunit from the eubacterium Deinococcus radiodurans with rapamycin, a
      polyketide compound resembling macrolides and ketolides, showed that rapamycin
      binds to a crevice located at the boundaries of the nascent protein exit tunnel,
      near its entrance. At this location rapamycin cannot occlude the ribosome exit
      tunnel, consistent with its failure to act as a ribosomal antibiotic drug. In
      accord with recent biochemical data, this crevice may play a role in facilitating
      local cotranslational folding of nascent chains, in particular for transmembrane
      proteins.

PMID- 15943965
TI  - The regulation of proteasome degradation by multi-ubiquitin chain binding
      proteins.
AB  - The 26S proteasome is a large multi-protein complex that functions to degrade
      proteins tagged with multi-ubiquitin chains. There are several mechanisms
      employed by the cell to ensure the efficient delivery of multi-ubiquitinated
      substrate proteins to the 26S proteasome. This is not only important to ensure
      the degradation of damaged and misfolded proteins, but also the regulated
      turnover of critical cell regulators. This discussion will concentrate on what is
      known about the recognition and delivery of ubiquitinated substrate proteins to
      the 26S proteasome.

PMID- 15943966
TI  - Oncogenic breakdowns in endocytic adaptor proteins.
AB  - Endocytosis is a versatile tool to regulate the intensity, localization, half
      life and function of signaling complexes (signalosomes) that form in cells upon
      binding of growth factors, cytokines and morphogens to their cognate receptors.
      Endocytic adaptors are non-catalytic proteins that assemble effectors and
      structural components of the endocytic machinery around the trafficking cargo and
      serve as scaffolds for signalosomes, which in turn modify their location and
      activity by various post-translational modifications. We discuss how breakdowns
      in the function of endocytic adaptors might facilitate impairment of tissue
      homeostasis and consequent tumor development.

PMID- 15943967
TI  - Plant CULLIN-based E3s: phytohormones come first.
AB  - CULLIN (CUL)-dependent ubiquitin ligases form a class of structurally related
      multi-subunit enzymes that control the rapid and selective degradation of
      important regulatory proteins involved in cell cycle progression and development,
      among others. Several classes of these E3s are also conserved in plants and
      genetic analyses, using Arabidopsis thaliana, indicate that they play an
      important function during plant development and responses to the environment. In
      this review, we will discuss the molecular composition and function of these
      enzymes in plants with a major emphasis on phytohormone signal transduction
      pathways.

PMID- 15943968
TI  - At the pulse of time: protein interactions determine the pace of circadian
      clocks.
AB  - Circadian clocks, internal timekeepers that generate a daily rhythmicity, help
      organisms to be prepared for periodic environmental changes of light and
      temperature. These molecular clocks are transcriptional feedback loops that
      generate 24-h oscillations in the abundance of clock proteins. For the
      maintenance of this rhythm inside the core clockwork and for its transmission to
      downstream genes the clock proteins additionally rely on post-transcriptional and
      post-translational mechanisms. Thus clock proteins engage in a variety of
      interactions with DNA, RNA and other proteins. Based on the model organisms
      Drosophila melanogaster and Arabidopsis thaliana molecular principles of
      circadian clocks are discussed in this review.

PMID- 15943969
TI  - Structure and functional role of supercomplexes of IsiA and Photosystem I in
      cyanobacterial photosynthesis.
AB  - Cyanobacteria express large quantities of the iron stress-inducible protein IsiA
      under iron deficiency. IsiA can assemble into numerous types of single or double
      rings surrounding Photosystem I. These supercomplexes are functional in light
      harvesting, empty IsiA rings are effective energy dissipaters. Electron
      microscopy studies of these supercomplexes show that Photosystem I trimers bind
      18 IsiA copies in a single ring, whereas monomers may bind up to 35 copies in two
      rings. Work on mutants indicates that the PsaF/J and PsaL subunits facilitate the
      formation of closed rings around Photosystem I monomers but are not obligatory
      components in the formation of Photosystem I-IsiA supercomplexes.

PMID- 15943970
TI  - Dosage compensation in flies: mechanism, models, mystery.
AB  - Dosage compensation involves fine-tuning of gene expression at the level of
      entire chromosomes. The principles that assure selective targeting of the male X
      chromosome in Drosophila and the mechanism by which transcription levels are
      adjusted in a twofold range are still mysterious. We discuss the prevalent models
      in the context of recent experimental observations.

PMID- 15943971
TI  - Compartmentalisation of phosphodiesterases and protein kinase A: opposites
      attract.
AB  - Understanding the molecular organisation of intracellular signalling pathways is
      a topic of considerable research interest. Since many signalling enzymes are
      widely distributed and have several substrates, a critical component in signal
      transduction is the control of specificity. This is achieved, in part by the
      assembly of multiprotein complexes where clusters of signalling enzymes create
      focal points to disseminate the intracellular action of many hormones. This is
      particularly true for the cAMP dependent protein kinase (PKA) that is localised
      throughout the cell via its association with A-kinase anchoring proteins (AKAPs).
      Recent data suggest that some AKAPs also interact with phosphodiesterases (PDEs).
      Compartmentalisation of PDEs not only provides an elegant means to control PKA
      activation by monitoring the local cAMP flux, but also serves to concentrate and
      segregate the action of these important regulatory enzymes.

PMID- 15943972
TI  - Second nature: biological functions of the Raf-1 "kinase".
AB  - More than 20 years ago, Raf was discovered as a cellular oncogene transduced by
      transforming retroviruses. Since then, the three Raf isoforms have been
      intensively studied, mainly as the kinases linking Ras to the MEK/ERK signaling
      module. As this pathway is activated in human cancer, the Raf kinases are
      considered promising therapeutic targets, and we have learned a lot about their
      regulation, targets, and functions. Do they still hold surprises? Recent gene
      targeting studies indicate that they do. This review focuses on the regulation
      and biology of the best-studied Raf isoform, Raf-1, in the context of its kinase
      independent functions.

PMID- 15943973
TI  - Proteolytic mechanisms in necrotic cell death and neurodegeneration.
AB  - Programmed neuronal cell death is required during development to achieve the
      accurate wiring of the nervous system. However, genetic or accidental factors can
      lead to the premature, non-programmed death of neurons during adult life.
      Inappropriate death of cells in the nervous system is the cause of multiple
      neurodegenerative disorders. Pathological neuronal death can occur by apoptosis,
      by necrosis or by a combination of both. Necrotic cell death underlies the
      pathology of devastating neurological diseases such as neurodegenerative
      disorders, stroke or trauma. However, little is known about the molecular
      mechanisms that bring about necrotic cell death. Proteases play crucial roles in
      neuron degeneration by exerting both regulatory and catabolic functions. Elevated
      intracellular calcium is the most ubiquitous feature of neuronal death with the
      concomitant activation of cysteine calcium-dependent proteases, calpains.
      Calpains and lysosomal, catabolic aspartyl proteases, play key roles in the
      necrotic death of neurons. In this review, we survey the recent literature on the
      role of cysteine and aspartyl proteases in necrosis and neurodegeneration, aiming
      to delineate common proteolytic mechanisms mediating cellular destruction.

PMID- 15943974
TI  - Transglutaminase 2 in the balance of cell death and survival.
AB  - Transglutaminase 2 (TG2), a multifunctional enzyme with Ca(2+)-dependent protein
      crosslinking activity and GTP-dependent G protein functions, is often upregulated
      in cells undergoing apoptosis. In cultured cells TG2 may exert both pro- and anti
      apoptotic effects depending upon the type of cell, the kind of death stimuli, the
      intracellular localization of the enzyme and the type of its activities switched
      on. The majority of data support the notion that transamidation by TG2 can both
      facilitate and inhibit apoptosis, while the GTP-bound form of the enzyme
      generally protects cells against death. In vivo studies confirm the Janus face of
      TG2 in the initiation of the apoptotic program. In addition, they reveal a
      further role: the prevention of inflammation, tissue injury and autoimmunity once
      the apoptosis has already been initiated. This function of TG2 is partially
      achieved by being expressed and activated also in macrophages digesting apoptotic
      cells and mediating a crosstalk between dying and phagocytic cells.

PMID- 15943975
TI  - Understanding the enzymology of fibrinolysis and improving thrombolytic therapy.
AB  - Cardiovascular disease is responsible for 17 million deaths per year but acute
      myocardial infarction and stroke can be treated with thrombolytics ("clot
      busters"), which are plasminogen activators. However, despite many years of study
      and huge investment from the pharmaceutical industry, clinical trials of new
      drugs have often been disappointing. Part of the problem may be our incomplete
      understanding of the regulation of plasminogen activation in vivo. We have
      developed precise in vitro methods and with the application of computer
      simulations, we hope to improve our understanding of plasminogen activation to
      facilitate improvements in thrombolytic therapy.

PMID- 15943976
TI  - The anticoagulant protein C pathway.
AB  - The anticoagulant protein C system regulates the activity of coagulation factors
      VIIIa and Va, cofactors in the activation of factor X and prothrombin,
      respectively. Protein C is activated on endothelium by the thrombin
      thrombomodulin-EPCR (endothelial protein C receptor) complex. Activated protein C
      (APC)-mediated cleavages of factors VIIIa and Va occur on negatively charged
      phospholipid membranes and involve protein cofactors, protein S and factor V. APC
      also has anti-inflammatory and anti-apoptotic activities that involve binding of
      APC to EPCR and cleavage of PAR-1 (protease-activated receptor-1). Genetic
      defects affecting the protein C system are the most common risk factors of venous
      thrombosis. The protein C system contains multi-domain proteins, the molecular
      recognition of which will be reviewed.

PMID- 15943977
TI  - Meprin metalloprotease expression and regulation in kidney, intestine, urinary
      tract infections and cancer.
AB  - Meprins are unique plasma membrane and secreted metalloproteinases that are
      highly regulated at the transcriptional and post-translational levels. Meprin
      alpha and beta subunits are abundantly expressed in kidney and intestinal
      epithelial cells, are secreted into the urinary tract and intestinal lumen, and
      are found in leukocytes and cancer cells under certain conditions. Their location
      and proteolytic activities indicate functions at the interface of the host and
      the external environment, and in trafficking of macrophages and metastases of
      cancer cells. These proteases can be detrimental when there is tissue damage or
      disruption, as in acute renal injury or intestinal inflammation, and there is
      evidence they are involved in movement of leukocytes and cancer cells to sites of
      infection or in metastasis, respectively.

PMID- 15943978
TI  - The matrilins--adaptor proteins in the extracellular matrix.
AB  - The matrilins form a four-member family of modular, multisubunit matrix proteins,
      which are expressed in cartilage but also in many other forms of extracellular
      matrix. They participate in the formation of fibrillar or filamentous structures
      and are often associated with collagens. It appears that they mediate
      interactions between collagen-containing fibrils and other matrix constituents,
      such as aggrecan. This adaptor function may be modulated by physiological
      proteolysis that causes the loss of single subunits and thereby a decrease in
      binding avidity. Attempts to study matrilin function by gene inactivation in
      mouse have been frustrating and so far not yielded pronounced phenotypes,
      presumably because of the extensive redundancy within the family allowing
      compensation by one family member for another. However, mutations in matrilin-3
      in humans cause different forms of chondrodysplasias and perhaps also hand
      osteoarthritis. As loss of matrilin-3 is not critical in mouse, these phenotypes
      are likely to be caused by dominant negative effects.

PMID- 15943979
TI  - Linear motifs: evolutionary interaction switches.
AB  - Linear motifs are short sequence patterns associated with a particular function.
      They differ fundamentally from longer, globular protein domains in terms of their
      binding affinities, evolution and in how they are found experimentally or
      computationally. In this Minireview, we discuss various aspects of these
      critically important functional regions.

PMID- 15943980
TI  - The interplay between structure and function in intrinsically unstructured
      proteins.
AB  - Intrinsically unstructured proteins (IUPs) are common in various proteomes and
      occupy a unique structural and functional niche in which function is directly
      linked to structural disorder. The evidence that these proteins exist without a
      well-defined folded structure in vitro is compelling, and justifies considering
      them a separate class within the protein world. In this paper, novel advances in
      the rapidly advancing field of IUPs are reviewed, with the major attention
      directed to the evidence of their unfolded character in vivo, the interplay of
      their residual structure and their various functional modes and the functional
      benefits their malleable structural state provides. Via all these details, it is
      demonstrated that in only a couple of years after its conception, the idea of
      protein disorder has already come of age and transformed our basic concepts of
      protein structure and function.

PMID- 15943981
TI  - Consistency of genome-based methods in measuring Metazoan evolution.
AB  - Seven distinct genome-wide divergence measures were applied pairwise to the nine
      sequenced animal genomes of human, mouse, rat, chicken, pufferfish, fruit fly,
      mosquito, and two nematode worms (Caenorhabditis briggsae and Caenorhabditis
      elegans). Qualitatively, all of these divergence measures are found to correlate
      with the estimated time since speciation; however, marked deviations are observed
      in a few lineages. The distinct genome divergence measures also correlate well
      among themselves, indicating that most of the processes shaping genomes are
      dominated by neutral events. The deviations from the clock-like scenario in some
      lineages are observed consistently by several measures, implicitly confirming
      their reliability.

PMID- 15943982
TI  - Laparoscopic surgery in gynecologic oncology--some disputable applications and
      one fruitful indication.

PMID- 15943983
TI  - Clinical significance of lympho vascular space involvement and lymph node
      micrometastases in early-stage cervical cancer: a retrospective case-control
      surgico-pathological study.
AB  - OBJECTIVE: Several studies have shown that lympho vascular space involvement
      (LVSI) and lymph node micrometastases (LNmM) may be risk factors for recurrence
      in early-stage cervical cancer with no apparent lymph node metastases. We
      performed a retrospective case-control study to reassess whether the presence of
      lymph node micrometastases and LVSI is predictive of subsequent recurrence
      following surgical resection of early-stage cervical cancer. METHODS: In a series
      of 292 patients diagnosed with early cervical cancer and treated by the same
      surgical procedure (laparoscopic-vaginal radical hysterectomy) during the same
      time period, two paired series were selected. The first series consisted of 26
      cases who recurred in a median time of 36.8 months and the second series were 26
      cases matched for age, histological sub-type, surgico-pathological stage and
      maximal tumor diameter, who did not recur after a median follow-up of 122 months.
      Sections taken from the hysterectomy specimens were reassessed for LVSI. All the
      lymph node blocks which have initially been considered as uninvolved were
      submitted to serial sectioning. Immunohistochemical staining using anti
      cytokeratins AE1 and AE3 was used for identifying LNmM. RESULTS: LVSI was twice
      more frequent and LNmM ten-fold more frequent in the group of patients who
      recurred: 20/26 (77%) versus 9/26 (35%) and 11/26 (42%) versus 1/26 (4%)
      respectively. The relative risk of recurrence is 2.64 (1.67-5.49, P < 0.01) in
      the presence of LVSI and 2.44 (1.58-3.78, P < 0.01) in the presence of LNmM. All
      the patients with LNmM were LVSI positive. At bivariate analysis, the true LNmM
      (deposits more than 200 um in size) was the only independent risk factor.
      CONCLUSIONS: LNmM is an important risk factor of tumor recurrence in patients
      with early cervical cancer with no apparent lymph node metastases. LNmM seems to
      occur only in LVSI positive tumors. These data may lead to improve management of
      early-stage cervical cancer to reduce the risk of recurrence in those cases.

PMID- 15943984
TI  - Recurrent smear abnormalities where repeat loop treatment is not possible: is
      hysterectomy the answer?
AB  - OBJECTIVE: The objective of this study was to determine the outcome of women who
      underwent hysterectomy for recurrent cytological abnormalities where repeat loop
      treatment was considered not to be technically possible because of insufficient
      remaining cervical tissue. METHODS: Women undergoing a hysterectomy for the above
      indication at the Northern Gynaecological Cancer Centre over a period of 10 years
      (1992-2001) were identified from a prospectively collected database. Case notes
      were then reviewed and women undergoing hysterectomy for other indications were
      excluded. Relevant demographic and clinical data were then extracted. RESULTS: 33
      patients meeting the above criteria were identified. The overall hysterectomy
      rate for this indication was 0.73%. 20 out of the 33 women had significant
      pathology on the hysterectomy specimen. 95% of these had high-grade disease with
      one having a Stage 1A1 squamous carcinoma. None of the patients required more
      radical treatment than a simple hysterectomy. There were no major complications
      following the hysterectomy. Positive endocervical margins on the previous loop
      specimen (P = 0.05) was an important correlating factor predicting the presence
      of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%)
      performed using the vaginal route had incomplete excision compared to one of
      three (33%) using the abdominal route. Hysterectomy was successful in treating
      85.2% of the women; only 4 women subsequently developed vaginal intraepithelial
      neoplasia. CONCLUSION: Simple hysterectomy appears to be a suitable diagnostic
      and treatment option for women with recurrent high-grade cytological
      abnormalities where further loop treatment is technically not possible.
      Incomplete excision at the endocervical margin on the previous loop specimen was
      the main factor associated with the presence of cervical intraepithelial
      neoplasia at hysterectomy.

PMID- 15943985
TI  - Radiation therapy induced micronuclei in cervical cancer--does it have a
      predictive value for local disease control?
AB  - OBJECTIVE: To evaluate the predictive value of serial changes in micronuclei
      induction during external radiotherapy (EXRT) in cervical cancer with respect to
      local response at the end of EXRT and local disease free survival (LDFS).
      METHODS: Twenty-five patients of squamous cell cancer of the cervix were treated
      by 50 Gy of EXRT delivered over 5 weeks followed by intracavitary brachytherapy.
      Serial cytological smears were taken from cervical growth at weekly intervals
      during the course of EXRT and stained by Giemsa and May-Grunwald's stain.
      Micronuclei induction were scored as (a) number of cells expressing micronuclei
      (MN), and (b) total number of micronuclei (TMN) in 1000 tumor cells from each of
      the serial smears. RESULTS: A significant rise in micronuclei count was seen for
      both MN and TMN from pretreatment (week 0) to successive weeks of EXRT. For those
      having a near total tumor regression by end of EXRT, a significant rise in
      micronuclei was evident even at the end of first week of EXRT (MN: P = 0.05, TMN:
      P = 0.04). A superior LDFS was observed in patients showing greater than 50%
      increment in MN value in the first week (median survival for <50% vs. > or =50%
      rise: 5 months vs. not reached, P = 0.21), while it reached significance for a
      similar rise of TMN (median survival <50% vs. > or =50% rise: 5 months vs. not
      reached, P = 0.04). CONCLUSIONS: The significant rise of micronuclei at the end
      of first week of EXRT in cervical cancers as observed from serial cytological
      smears could predict for a better local response and LDFS.

PMID- 15943986
TI  - Association between RCAS1 expression and microenvironmental immune cell death in
      uterine cervical cancer.
AB  - OBJECTIVE: : The presence of regional lymph node metastasis is one of the
      prognostic factors for uterine cervical cancer. The development of metastasis
      requires that cancer cells avoid lymphocyte attack. Impaired lymphocyte function
      is mediated by apoptotic factors including receptor-binding cancer antigen
      expressed on SiSo cells (RCAS1), Fas ligand (FasL), and tumor necrosis factor
      alpha (TNF-alpha). Our aim was to evaluate the association between expression of
      these factors and microenvironmental lymphocyte apoptosis in this disease.
      METHODS: : Immunohistochemical methods were used to determine the relationship
      between the expression of RCAS1, FasL, and TNF-alpha, and the number of apoptotic
      lymphocytes in primary lesions and metastatic lymph nodes in patients with
      cervical cancer. RESULTS: : Expression of these apoptosis-inducing molecules was
      quite different in primary tumors and metastatic lymph nodes: RCAS1 expression in
      lymph nodes was significantly higher than that in primary lesions (P < 0.0001),
      whereas FasL and TNF-alpha expressions at these two locations were not
      significantly different. The number of cells with positive expression of RCAS1,
      but not of FasL or TNF-alpha, was significantly correlated with the number of
      apoptotic lymphocytes in uterine cervix and metastatic lymph nodes (P < 0.0001
      for both). CONCLUSION: : RCAS1 expression may be related to tumor cell evasion of
      immune surveillance via induction of lymphocyte apoptosis in primary lesions and
      metastatic lymph nodes in uterine cervical cancer.

PMID- 15943987
TI  - Ovarian carcinoma cells and IL-1beta-activated human peritoneal mesothelial cells
      are possible sources of vascular endothelial growth factor in inflammatory and
      malignant peritoneal effusions.
AB  - OBJECTIVE: Inflammatory or malignant peritoneal diseases are associated with high
      levels of ascitic vascular endothelial growth factor (VEGF). We compared the VEGF
      secretion by human peritoneal mesothelial cells (HPMC) and ovarian carcinoma
      (OVCA) cells and its regulation by pro-inflammatory cytokines. MATERIALS AND
      METHODS: VEGF secretion in cultured HPMC, established human OVCA cell lines, and
      inflammatory or OVCA-associated ascites was determined by enzyme linked
      immunosorbent assay. RESULTS: HPMC constitutively produced VEGF at median levels
      of 43 +/- 7 pg/10(5) cells. Treatment of HPMC with 1 ng/ml IL-1beta (567 +/- 213
      pg/10(5) cells) or TNF-alpha (89 +/- 1 pg/10(5) cells) resulted in a 13-fold (P <
      0.01) or 2-fold (P < 0.05) elevation of the VEGF secretion. In OVCA, the
      constitutive VEGF expression was 8-fold higher than VEGF levels in HPMC (364 +/-
      185 pg/10(5) cells; P < 0.001). VEGF secretion in OVCA cells was also increased
      by IL-1beta (514 +/- 105 pg/10(5) cells; P < 0.01) or TNF-alpha (458 +/- 168
      pg/10(5) cells; P < 0.01) reaching similar levels as in IL-1beta-activated HPMC.
      Median VEGF levels in malignant ascites (2761 +/- 1549 pg/ml) were 11-fold higher
      compared with levels in inflammatory fluids (244 +/- 170 pg/ml; P < 0.01). VEGF
      levels in both inflammatory- and OVCA-associated fluids correlated with ascitic
      IL-1beta levels (P < 0.05). CONCLUSION: We identified ovarian cancer cells and/or
      IL-1beta-activated peritoneal mesothelial cells as important sources of ascitic
      VEGF. The present data indicate that IL-1beta-triggered VEGF production by
      neoplastic and normal cells is a common pathomechanism for ascites formation in
      both inflammatory and malignant conditions.

PMID- 15943988
TI  - Laparoscopic lymphadenectomy for gynecologic malignancies using ultrasonically
      activated shears: analysis of first 100 cases.
AB  - OBJECTIVE: To evaluate the feasibility, safety and utility of the ultrasonic
      shears for laparoscopic pelvic and para-aortic lymph node retrieval in the
      treatment of gynecologic cancers. METHODS: Data on laparoscopic lymphadenectomy
      performed for gynecologic malignancies using ultrasonic shears over a 5-year
      period were collected and analyzed prospectively. RESULTS: Laparoscopic
      lymphadenectomy using ultrasonic shears was performed on 100 patients with a
      median age of 58 (17-87) years. The types of malignancies included cervical (n =
      29), endometrial (n = 48), ovarian (n = 15), fallopian tube (n = 2), malignant
      mixed mesodermal tumor (n = 2), vaginal (n = 2) and synchronous ovarian and
      endometrial cancers (n = 2). Sites of lymphadenectomy included pelvic (n = 49),
      para-aortic (n = 30) or both pelvic and para-aortic (n = 21). The median nodal
      yield was 22 (0-87). 66/100 were complete lymphadenectomies with a median nodal
      yield of 28 (2-71). The median length of hospital stay was 2 (1-13) days and the
      average blood loss was 148 (0-500) ml. Overall complication rate was 13%. There
      were 3 intra-operative complications, which were all managed laparoscopically.
      There were no unplanned conversions to laparotomy. There were 10 post-operative
      complications including port-site metastasis in a patient with positive nodes (n
      = 1), trocar-site hernia requiring a second laparoscopy (n = 1), deep leg vein
      thrombosis (n = 1), and a small bowel obstruction (n = 1). CONCLUSIONS: This is
      the largest series to date demonstrating the safety and efficacy of ultrasonic
      shears in laparoscopic lymphadenectomy for gynecologic malignancies. In addition
      to the potential for lowering the risk for tissue damage, ultrasonic shears offer
      multifunctionality which allows for a simpler technique with the use of fewer
      instruments.

PMID- 15943989
TI  - Division of pedicles by stapling during cytoreductive surgery for ovarian cancer.
AB  - OBJECTIVE: To determine the potential of dividing vascular pedicles by stapling
      to reduce operative time, blood loss, and morbidity associated with cytoreductive
      operations for advanced ovarian cancer. METHODS: A case-control study was
      undertaken to compare operative outcomes for patients undergoing primary
      cytoreductive operations for ovarian cancer using two different operative
      strategies. Between 2002 and 2004, both stapling and conventional techniques were
      used to divide vascular pedicles for 50 consecutive patients requiring modified
      posterior exenterations (en-bloc resection of internal reproductive organs,
      pelvic peritoneum, and recto-sigmoid colon) and upper abdominal procedures in the
      context of primary cytoreduction for stage IIIC and IV ovarian cancer. The
      operative time, blood loss, transfusion rate, hospitalization, and incidence of
      complications were compared to outcomes of 50 consecutive patients operated on
      between 1994 and 1997 for whom stapling was not used to divide pedicles (chi
      square test for binomial data, and t-test analysis for continuous data). RESULTS:
      Both groups were equivalent with respect to disease severity, extent of upper
      abdominal surgery, and cytoreductive outcomes. The group for whom stapling
      devises were used to divide pedicles had a significantly reduced total operative
      time 179 min vs. 284 min, P < 0.001), estimated blood loss (1170 ml vs. 1782 ml,
      P = 0.004), and transfusion rate (3.6 units packed red cells vs. 5.0 units packed
      red blood cells, P = 0.03). CONCLUSION: Stapling of vascular pedicles
      significantly reduces the operative time and blood loss for patients undergoing
      extensive primary cytoreductive operations for advanced ovarian cancer.

PMID- 15943990
TI  - Gamma-knife radiosurgery for the treatment of ovarian cancer metastatic to the
      brain.
AB  - BACKGROUND: Central nervous system (CNS) metastases from an ovarian malignancy
      are uncommon. The long-term prognosis for these patients is poor, with studies
      reporting a mean survival of less than 12 months. CASES: We present three ovarian
      cancer patients who developed metastatic disease to the brain. All patients were
      heavily pre-treated prior to the development of CNS disease. Following detection
      of CNS disease, they all were treated with multi-modality therapy including gamma
      knife radiosurgery (GKRS). At this time, one patient is alive at 26 months
      following treatment with GKRS. The second and third patients survived for 88 and
      22 months respectively, before succumbing to their disease. CONCLUSION: Local
      control of ovarian cancer metastatic to the brain can be achieved in some
      patients with GKRS. Additional investigation into GKRS is warranted.

PMID- 15943991
TI  - Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation
      for early stage endometrial cancer.
AB  - OBJECTIVE: Postoperative management of early stage adenocarcinoma of the
      endometrium remains controversial. The use of pelvic radiation therapy as shown
      by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval
      at the cost of increased toxicity. We reviewed and compared our results treating
      early stage endometrial adenocarcinoma using hypofractionated high dose rate
      (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. METHODS:
      From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and
      selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these,
      50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of
      the endometrium were managed with HDR hypofractionated VB as monotherapy using
      Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth
      of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and
      outcomes of our patients were compared with the results of the GOG-99. The median
      follow up of our patients and the GOG-99 were 3.2 years and 5.8 years,
      respectively. RESULTS: Patient characteristics including age, stage, and grade
      were similar in our study and the GOG-99. The local recurrence rate in our study,
      the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2),
      2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in
      the vagina alone and a second patient failed in the vagina and pelvis. In the GOG
      99, the vagina as a component of locoregional failure was also the most common
      failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The
      2-year cumulative recurrence rate in our study was 2%, which compares favorably
      with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival
      rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study
      with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates
      were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0%
      vs. 34% (P value < 0.001), and GI obstruction 0% vs. 7% (P value = 0.08).
      CONCLUSION: Stage I-II (occult) endometrial adenocarcinoma treated with
      postoperative HDR vaginal brachytherapy has similar overall survival,
      locoregional failure rates, and cumulative recurrence rates to standard
      fractionation external beam pelvic RT with the benefit of much lower toxicity
      rates and shorter overall treatment time.

PMID- 15943992
TI  - DNA- versus RNA-based methods for human papillomavirus detection in cervical
      neoplasia.
AB  - OBJECTIVE: To compare DNA-based and mRNA-based methods for detection of high
      grade cervical neoplasia in Norway. METHODS: HPV prevalence was analyzed in 383
      women with positive index cytology, selected from gynecology clinics. All
      patients were investigated by a new PAP smear, histology, and two commercially
      available HPV tests: Hybrid Capture II (Digene, Gaithersburg, MD) and the Pre
      Tect HPV-Proofer (NorChip AS). Cases with positive DNA test and negative mRNA
      test and cases with high-grade histology and negative HPV tests were retested
      with PCR and sequencing. We regarded the infection as latent or transient if
      sequencing revealed an HPV type included in both assays. RESULTS: High-risk HPV
      was detected in 99.7% of the histological confirmed high-grade lesions (CIN2+)
      (290/291). The DNA test was positive in 95% (275/291), and the mRNA test was
      positive in 77% (225/291) of the histological confirmed high-grade lesions. All
      invasive carcinomas were mRNA positive. The DNA test was significantly more often
      positive in benign and low-grade lesions, some of which were found to be false
      positive due to cross-contamination with unrelated types. High-grade histology
      was detected in 83% of women with normal cytology and positive mRNA test. Latent
      or transient infections were detected in 11 low-grade and 12 high-grade
      preinvasive lesions. Sequencing revealed high-risk HPV types included only in the
      DNA test in 35 high-grade preinvasive lesions, HPV 52 and 58 were the most
      prevalent HPV types. CONCLUSIONS: These HPV tests have the potential to improve
      the detection rate of high-grade cervical neoplasia, with some limitations. The
      mRNA test seems to be more appropriate for risk-evaluation. Larger scale,
      population based studies are necessary to evaluate the predictive values of HPV
      testing in Norway.

PMID- 15943993
TI  - Is levonorgestrel intrauterine system effective for treatment of early
      endometrial cancer? Report of four cases and review of the literature.
AB  - BACKGROUND: Intrauterine progesterone therapy potentially provides a simple
      alternative treatment for women with Stage I Grade I endometrial cancers who are
      at high risk for surgery. The case histories of four women with early endometrial
      cancer primarily treated with levonorgestrel intrauterine system (Mirena) are
      reported and the literature reviewed. CASES: Four women had Stage I grade 1
      endometrial adenocarcinoma with positive progesterone receptor. All were assessed
      to be in American Society of anaesthesiologists risk class IV. After insertion of
      mirena intrauterine system, one woman (25%) had complete histological regression
      of disease within 6 months. One of three women who did not respond to treatment
      subsequently had a vaginal hysterectomy, which showed endometrial cancer with
      superficial myometrial invasion. CONCLUSION: This report raises doubts about the
      effectiveness of intrauterine progesterone therapy as a definitive alternative
      for the treatment of early endometrial cancer.

PMID- 15943994
TI  - Gastric adenocarcinoma presenting as uterine metastasis--a case report.
AB  - BACKGROUND: Metastases to the uterus are rare, especially from extrapelvic
      malignancies. CASE: We report a 75-year-old woman who underwent hysterectomy for
      a FIGO Grade I endometrial carcinoma and was found to have evidence of a second
      malignant process involving the myometrium. The patient underwent a gastroscopy,
      which showed nonspecific superficial gastric and duodenal erosions. Random
      biopsies, however, confirmed a diagnosis of primary gastric adenocarcinoma. CT
      scan also showed pulmonary metastasis. The patient developed progressive disease
      despite two cycles of chemotherapy consistent of etoposide, doxorubicin and
      carboplatin. CONCLUSION: This case illustrates the presence of two spatially
      separated tumours found in the uterus. Malignant cells present deep in the
      lymphovascular spaces have morphological features different from the primary
      endometrial carcinoma. The microscopic appearances of these cells are similar to
      that of the gastric biopsy, supporting the diagnosis of metastatic gastric
      adenocarcinoma.

PMID- 15943996
TI  - Metastatic carcinoma of the gallbladder mimicking an advanced cervical carcinoma.
AB  - BACKGROUND: Metastasis to the uterine cervix from a non-gynecologic neoplasm is
      extremely rare. To our knowledge, only three cases of primary carcinoma of the
      gallbladder with metastasis to the cervix have been previously reported. We
      report a case of metastatic gallbladder carcinoma mimicking a stage IIIB cervical
      carcinoma. CASE: A 74 year-old woman presented with pain in her left lumbar area
      radiating to her left flank. On physical examination, a 6 cm cervical tumor
      involving the left parametrium was noted. A computed tomography (CT) scan of the
      pelvis showed left-sided hydronephrosis and hydroureter with distal ureteral
      obstruction. A Pap smear revealed adenocarcinoma, and a biopsy of the
      endocervical canal was consistent with poorly differentiated adenocarcinoma. The
      patient was referred to a tertiary care center. On review of the biopsy after
      referral, the carcinoma was felt to be unusual for an endocervical primary and
      immunohistochemical stains were ordered. The carcinoma was positive for
      cytokeratin 7, had only focal cytoplasmic staining for p16, and was negative for
      carcinoembryonic antigen and cytokeratin 20. Upon presentation, the patient
      complained of new onset of shortness of breath and cough. A chest CT revealed
      multiple lesions in both lungs suggestive of metastatic disease, and an abdominal
      CT revealed a gallbladder tumor with extension into the liver. The patient
      underwent a CT-guided biopsy of one of the lung lesions and the pathologic
      findings were consistent with metastatic adenocarcinoma. The patient was
      diagnosed with stage IVB primary gallbladder adenocarcinoma and was treated with
      capecitabine, but her condition deteriorated rapidly and she died 5 months later.
      CONCLUSION: In patients with an atypical presentation for cervical
      adenocarcinoma, it is important to consider a metastatic tumor in the
      differential diagnosis and to perform a thorough work-up for metastatic disease
      before initiating therapy.

PMID- 15943995
TI  - Pregnancy following recurrent angiosarcoma of the ovary--a case report and review
      of literature.
AB  - BACKGROUND: Ovarian angiosarcomas are rare tumors which may to be distinguished
      from other unusual primary ovarian tumors such as clear cell carcinoma, yolk sac
      tumor and leiomyosarcoma on the basis of histological appearance and
      immunohistochemistry. Angiosarcomas of the ovary occur in all age groups but are
      more frequent in women of child bearing age (less than 40 years). Surgery and
      radiotherapy have been the traditional treatment modalities. CASE: The case we
      present is the only reported long-term survivor of recurrent ovarian
      angiosarcoma. Her initial treatment was surgical, both at presentation and
      relapse but since she wished conservation of fertility, radical surgery and
      radiotherapy were avoided and she underwent further adjuvant chemotherapy with
      doxorubicin and ifosfamide. She remains in remission 6 years after treatment of
      recurrence of the primary tumor and has had a successful pregnancy following
      treatment. CONCLUSION: Adjuvant chemotherapy of ovarian angiosarcoma with a
      combination of doxorubicin and ifosfamide appears effective and should be
      considered in women at risk of relapse who wish to conserve fertility.

PMID- 15943997
TI  - Uterine gastrointestinal stromal tumour (GIST).
AB  - BACKGROUND: Gastrointestinal stromal tumours (GIST) are mesenchymal tumours which
      mostly arise in the gastrointestinal tract showing positive CD117
      immunohistochemical staining. In recent years, other locations such as the
      mesentery and the retroperitoneum have been reported. CASE: A 77-year-old woman
      presented with a pelvic mass, raising the suspicion of an ovarian or a uterine
      tumour. During laparotomy, a ruptured process arising from the uterus was seen
      and removed. Histologic features, immunophenotype and genotype of the tumour
      supported the diagnosis of a GIST. CONCLUSIONS: To the best of our knowledge,
      this is the first case of a primary GIST presenting as a uterine mass. Because of
      recent advances in GIST-therapy, making a correct diagnosis has major clinical
      implications.

PMID- 15943998
TI  - Non-puerperal uterine inversion associated with endometrial carcinoma--a case
      report.
AB  - BACKGROUND: Non-puerperal uterine inversion is rare, and a case associated with
      endometrial carcinoma is even rarer. It is difficult to diagnose the condition
      preoperatively and most cases are diagnosed at surgery. CASE: We describe a case
      of uterine inversion associated with endometrial carcinoma. Initially, the
      patient was thought to have a cervical adenocarcinoma and treated with
      chemotherapy; however, a diagnosis of uterine inversion was made with magnetic
      resonance imaging (MRI) and ultrasonography during pre-surgical chemotherapy. We
      performed total abdominal hysterectomy, bilateral salpingo-oophorectomy, and
      bilateral pelvic lymphadenectomy. CONCLUSION: MRI and ultrasonography can be
      extremely useful tools for diagnosing uterine inversion.

PMID- 15943999
TI  - Laproscopic treatment of borderline ovarian tumors.

PMID- 15944000
TI  - Response to: Lavey, RS et al. Recombinant human erythropoietin as an adjunct to
      radiation therapy and cisplatin for stage IB-IVA carcinoma of the cervix: a
      Southwest Oncology Group Study. Gynecol. Oncol. 95 (2004) 145-151.

PMID- 15944001
TI  - Should lymphadenectomy be performed in patients with endometrial stromal sarcoma?

PMID- 15944002
TI  - Galanin receptor ligands.
AB  - The three galanin receptor subtypes (GalR1-3) belong to the G protein-coupled
      receptor superfamily. The widespread distribution of galanin and its receptors in
      the CNS and PNS and the numerous physiological and pharmacological effects of
      galanin (for review, cf. Vrontakis, 2002) render the three galanin receptors
      attractive drug targets. The industrial efforts, however, have not yet resulted
      in a wealth of receptor subtype specific agonists or antagonists with high
      affinity and selectivity. The present paper summarizes the properties of the
      galanin ligands used at the end of 2004 in the ca. 2000 publications and
      complements their pharmacological characterization with new data.

PMID- 15944003
TI  - Distribution and differential regulation of galanin receptor subtypes in rat
      brain: effects of seizure activity.
AB  - Galanin, acting at the GalR1-3 subtypes of galanin receptors, is involved in the
      regulation of cognition, mood, feeding, seizure activity and pain. The
      understanding of galanin's effects in molecular and cellular terms has been
      hampered by the lack of receptor subtype selective ligands and antibodies.
      Previous in situ hybridization data showed that GalR1 and GalR2 receptors are
      abundant in the rat brain, while the distribution of GalR3 is contradictory and
      most studies demonstrated a low expression levels in the rat brain. The
      distribution of galanin receptor subtypes at protein level is unknown. In the
      present study, we report the regional distribution of the galanin receptors:
      GalR1 and non-GalR1 receptors, using a recently synthesized high affinity GalR2/3
      selective ligand, galanin (2-11), and galanin (1-29), as competitors, in
      saturating (125)I-galanin membrane binding assay. We show that paraventricular
      nucleus (PVN) express predominantly GalR1, whereas areas like the dorsal raphe
      nucleus (DRN), hippocampus and amygdala express both the GalR1 and non-GalR1
      receptors. We speculate that the GalR2/3 binding sites detected by galanin (2-11)
      binding in our study probably represent mostly GalR2 receptors. In addition, we
      show regionally specific and subtype specific regulation of galanin receptors.
      Status epilepticus (SE), known to deplete galanin from axonal projections of
      locus coeruleus and septum/diagonal band neurons in the hippocampus and to induce
      galanin expression in a subset of hippocampal cells, down regulates GalR2
      receptor mRNA and proteins by 30% without altering the GalR1 receptors.

PMID- 15944004
TI  - G protein-coupled galanin receptor distribution in the rat central nervous
      system.
AB  - The action of galanin in the central nervous system is mediated by at least three
      galanin receptor subtypes (GalR1, GalR2 and GalR3) which belong to the family of
      G protein-coupled receptors. GalR1 and GalR2 are coupled to G(i/o) proteins,
      although the latter may also be coupled to G(q/11) proteins. The aim of the
      present study was to identify the anatomical distribution and quantify the
      density of GalRs coupled to G proteins. The galanin (10(-6) M) stimulated
      guanosine 5'-(gamma-[35S] thio)triphosphate binding assay was used in tissue
      sections from the rat brain. Maximal percentages of stimulation over basal levels
      were found in the anterior olfactory nucleus and in the lateral olfactory tract
      nucleus ( approximately 54%). High levels of stimulation were recorded in diverse
      hypothalamic nuclei (16-28%), in the amygdala (central amygdaloid nucleus, 40%),
      in the spinal trigeminal tract (23%) and in layers 1-2 of the spinal cord (26%).
      Moderate binding stimulation (5-13%) was observed in thalamus, substantia nigra
      pars compacta, parabrachial nucleus, locus coeruleus and dorsal raphe nucleus.
      The lowest stimulation induced by galanin was recorded in diverse areas of the
      cortex, striatum, hippocampus and substantia nigra pars reticulata. The results
      show an anatomical distribution similar to that described for GalR1. However, in
      diverse brain areas, in which a high density of these receptors has previously
      been reported, only a moderate coupling to G proteins was found. These findings
      would suggest that the efficacy of galanin to induce an effective coupling of its
      receptors to G proteins could be different depending on the brain area.

PMID- 15944005
TI  - Effects of central galanin administration on muscarinic cholinergic and galanin
      receptor G protein coupling.
AB  - The neuropeptide galanin is expressed in the mammalian central nervous system and
      has been implicated in neurotrophic actions. Central galanin administration
      induces cognitive deficits in rodents and inhibits the release of acetylcholine
      in the hippocampus. In addition, a galanin hyperinnervation of the basal
      forebrain cholinergic cells in Alzheimer's disease patients has been reported. To
      evaluate the effect of galanin treatment on galanin and muscarinic cholinergic
      receptor G protein coupling, galanin was administered into the lateral ventricle
      of rats via an implanted cannula. Galanin or muscarinic receptor functional
      coupling to G proteins was quantified by galanin or carbachol stimulation of
      guanosine 5'-(gamma-[35S]thio)triphosphate binding in rat brain slices. Guanosine
      5'-(gamma-[35S]thio)triphosphate basal binding in nucleus basalis of Meynert and
      thalamic nuclei was increased in the vehicle treated group. This effect was
      reverted by galanin treatment and indicates that the surgery increased receptor
      functional coupling to G proteins, which is restored by a possible neurotrophic
      action mediated by galanin. In addition, in galanin administered animals, galanin
      stimulated binding was increased in the amygdala but decreased in the diagonal
      band, whilst binding stimulation mediated by carbachol was found to be increased
      in the amygdala, thalamic nuclei and diagonal band. These findings indicate that
      galanin treatment modulates the coupling of galanin and muscarinic cholinergic
      receptors to G proteins in specific regions of the rat central nervous system.

PMID- 15944006
TI  - Galnon--a low-molecular weight ligand of the galanin receptors.
AB  - Galnon is a low-molecular weight galanin receptor ligand, with affinity towards
      the three galanin receptors in the micromolar range. Galnon is of interest as a
      drug candidate due to its stability and ability to pass the blood-brain barrier.
      Like galanin, galnon has also been shown to affect various physiological
      functions; however, occasionally galanin and galnon act in opposing ways. Since
      its introduction in 2002, galnon has been characterized to inhibit seizures,
      decrease feeding behaviour, diminish physical signs of opiate withdrawal and to
      alleviate heat-hyperalgesic response to partial sciatic nerve injury. In this
      review, we will summarize what is known about galnon to date.

PMID- 15944007
TI  - Galanin (2-11) binds to GalR3 in transfected cell lines: limitations for
      pharmacological definition of receptor subtypes.
AB  - The neuropeptide galanin regulates a variety of physiological and
      pathophysiological processes through three G protein coupled receptors, GalR1,
      GalR2, and GalR3. The studies on galanin receptor subtype specific effects have
      been hampered by the lack of high affinity subtype selective antagonist and/or
      agonist to any of these three galanin receptor subtypes. Since its recent
      introduction in 2003, galanin (2-11) has been widely used as a GalR2 selective
      agonist in several in vitro and in vivo studies. In the present paper, we
      demonstrate that galanin (2-11) binds to rat GalR3 receptors in transfected cell
      lines with a similar affinity as it binds to GalR2. As none of the available
      antagonists are galanin receptor subtype selective, as shown here for M35 and
      M40, more work is needed to confirm whether a galanin (2-11) effect is GalR2
      mediated and there is an urgent need for high affinity galanin receptor subtype
      selective ligands. For now one needs to interpret the data obtained at lower
      galanin (2-11) concentrations as effects mediated by non-GalR1 type galanin
      receptors, i.e., GalR2 and/or GalR3.

PMID- 15944008
TI  - Important pharmacophores for binding to galanin receptor 2.
AB  - Galanin(2-11) has been introduced as a receptor subtype selective ligand for the
      GalR2 subtype of the galanin receptors, and has gained use in pharmacological
      studies of galaninergic signaling in the past two years. By introducing l-Ala
      substitutions in the galanin(2-11) sequence, we have examined the amino acid
      residues which are of importance for binding to the GalR2 receptor. Our study
      shows that Trp2, Asn5, Gly8 and Tyr9 are of great importance for high affinity
      binding. When placed in an alpha-helical conformation, the side chains of these
      residues are, with the exception of Tyr9, displayed on the same "side" of the
      peptide. This information is useful in the rational design of non-peptide type
      GalR2 receptor ligands.

PMID- 15944009
TI  - Pharmacological and functional characterization of galanin-like peptide fragments
      as potent galanin receptor agonists.
AB  - The hypothalamic galanin-like peptide (GALP) was isolated by its ability to
      activate galanin receptors. The mature porcine GALP is a 60-amino acid
      neuropeptide proteolytically processed from a 120-amino acid precursor protein.
      It contains a region identical to the N-terminal 13-amino acids of the
      neuropeptide galanin. Within the sequence of human GALP (1-60) a potential
      proteolytic cleavage site between two basic amino acids is present at position
      33, which might lead to a shorter C-terminally amidated peptide. In addition, the
      first two amino acids could be potentially removed via the action of dipeptidase
      IV. Ligand binding assays using the human neuroblastoma cell line SH-SY5Y
      transfected with the respective galanin receptors revealed that human GALP (1-60)
      displayed the highest affinity for the galanin receptor subtype GalR3 (IC50 = 10
      nM) followed by GalR2 (IC50 = 28 nM) and GalR1 (IC50 = 77 nM). Ligand binding
      assays and functional studies showed that the human GALP (3-32) fragment was at
      least as potent as full length GALP (1-60). Other studies have shown that shorter
      fragments like human GALP (1-21) and GALP (22-60) were not effective on feeding
      responses in mice as compared to the full length peptide. Taken together these
      data suggest that the putative fragment GALP (3-32) might represent the strongest
      mediator of biological GALP activity. Furthermore it might be a useful tool to
      study the affinity of GALP to galanin receptors and to search for specific GALP
      receptors.

PMID- 15944010
TI  - Role of galanin and galanin(1-15) on central cardiovascular control.
AB  - Galanin and the N-terminal fragment Galanin(1-15) are involved in central
      cardiovascular regulation. The present paper reviews the recent cardiovascular
      results obtained by intracisternal injections of Galanin and Galanin(1-15)
      showing that: (A) the Galanin antagonist M40 blocks the central cardiovascular
      responses induced by Galanin(1-15) but not those elicited by Galanin; (B) both
      Galanin and Galanin(1-15) induce the expression of c-Fos in cardiovascular nuclei
      of the medulla oblongata with different temporal and spatial profiles; (C) the
      cardiovascular action of Galanin(1-15), but not Galanin, is mediated by
      peripheral beta-receptor stimulation; (D) and it is demonstrated an antagonistic
      Galanin/alpha2-adrenoceptors interaction as well as a differential modulation of
      central cardiovascular responses of Angiotensin II by Galanin or Galanin(1-15).
      All these data strengthen the involvement of both Galanin molecules as
      neuromodulators on central cardiovascular regulation.

PMID- 15944011
TI  - Use of genetically engineered transgenic mice to investigate the role of galanin
      in the peripheral nervous system after injury.
AB  - The neuropeptide galanin is present at high levels within the dorsal root ganglia
      (DRG) and spinal cord during development and after peripheral nerve damage in the
      adult. This pattern of expression suggests that it may play a role in the
      adaptive response of the peripheral nervous system (PNS) to injury. Several
      experimental paradigms have demonstrated that galanin modulates pain
      transmission, particularly after nerve injury. In our laboratory we have used a
      transgenic approach to further elucidate the functions of galanin within the
      somatosensory system. We have generated mice which over-express galanin (either
      inducibly after nerve injury, or constitutively), and knock-out (KO) mice, in
      which galanin is absent in all cells, throughout development and in the adult.
      Analysis of the nociceptive behaviour of the galanin over-expressing animals,
      before and after nerve injury, supports the view that galanin is an inhibitory
      neuromodulator of spinal cord transmission. In apparent contradiction to these
      findings, galanin KO animals fail to develop allodynia and hyperalgesia after
      nerve injury. However, further studies have shown that galanin is critical for
      the developmental survival of a subset of small diameter, unmyelinated sensory
      neurons that are likely to be nociceptors. This finding may well explain the lack
      of neuropathic pain-like behaviour after injury in the KO animals. Furthermore,
      the developmental survival role played by galanin is recapitulated in the adult
      where the peptide is required for optimal neuronal regeneration after injury, and
      in the hippocampus where it plays a neuroprotective role after excitotoxic
      injury.

PMID- 15944012
TI  - Galanin in neuro(glio)genesis: expression of galanin and receptors by progenitor
      cells in vivo and in vitro and effects of galanin on neurosphere proliferation.
AB  - Considerable recent evidence suggests that in addition to its neuromodulatory
      role, galanin, like several other neuropeptides, also plays an important trophic
      role during development and after adult neural injury. Studies in our laboratory
      have identified high levels of galanin and galanin receptor expression in the
      subventricular zone, rostral migratory stream, subgranular zone of dentate gyrus
      and the medial corpus callosum--which include the main sites for continuing cell
      proliferation in both adult and developing rat brain. Galanin expression was also
      strongly and transiently induced in oligodendrocyte progenitor cells (OPCs)
      throughout the neocortex and corpus callosum by a benign physiological stimulus,
      cortical spreading depression (CSD). SD-like depolarization also occurs in peri
      infarction areas following cerebral ischemia and is associated with proliferation
      of OPCs and transiently increased galanin expression. Together, these data
      suggest a putative role for galanin in regulating progenitor or 'stem cell'
      proliferation, migration and/or differentiation. Cultured adult and embryonic
      stem cells or 'neurospheres' express galanin and galanin receptor mRNA and
      preliminary studies suggest that sub-acute galanin treatment of cultured
      neurospheres decreases cell proliferation/survival, possibly by effects on the
      rate of apoptosis via GalR2 receptors.

PMID- 15944013
TI  - Galanin and spinal nociceptive mechanisms: recent results from transgenic and
      knock-out models.
AB  - Genetically modified mice with transgenic overexpression of galanin or depletion
      of genes for galanin or galanin receptors have become available, providing a new
      approach for analyzing the role of galanin in nociception. Mice overexpressing
      galanin had a moderate heat hypoalgesia, reduced spinal sensitization after
      repetitive C-fiber stimulation and reduced development of neuropathic pain-like
      behavior after sciatic nerve injury. On the other hand, mice lacking the GALR1
      receptor (Galr1-/-) exhibited only slight increase in heat nociception in the hot
      plate, but not tail flick, test and showed no increase in spinal sensitization.
      The duration, but not magnitude, of neuropathic pain-like behaviors, was
      increased in Galr1-/- mice after nerve injury. These results support an
      inhibitory effect of galanin on nociception, but the physiological role played by
      galanin via GALR1 receptors needs to be further studied.

PMID- 15944014
TI  - Mechanisms of antinociception of spinal galanin: how does galanin inhibit spinal
      sensitization?
AB  - Galanin by a spinal action has been shown to have an antihyperalgesic action.
      Thus, in rats with lumbar intrathecal (IT) catheters, the thermal hyperalgesia
      evoked by carrageenan paw injection was blocked by IT delivery of galanin(1-29)
      (Gal(1-29)) and galanin(2-11) (Gal(2-11)) with the rank order of activity being
      Gal(1-29)>Gal(2-11). We sought to determine whether this spinal action reflects
      an effect upon afferent transmitter release, e.g., substance P (SP), and/or on
      secondary neurons, e.g., signaling postsynaptic to neurokinin 1 (NK1) receptor
      activation. To address the question on afferent release, we investigated the
      effect of IT administration of galanin on tissue injury-induced spinal NK1
      internalization (an indicator of SP release). Noxious stimulation (paw
      compression) produced an increase in NK1 internalization in dorsal horn lamina I.
      IT pretreatment of rats with Gal(1-29) and Gal(2-11) significantly attenuated the
      evoked NK1 internalization, with the rank order of activity being Gal(1-29)>Gal(2
      11)>saline. To address the question of postsynaptic action, we examined the
      effects of IT galanin upon IT SP-induced thermal hyperalgesia and spinal PGE2
      release. Application of SP (30 nmol) directly to spinal cord led to a decrease in
      thermal thresholds and a profound increase in PGE(2) concentration in spinal
      dialysates. Both phenomena were reversed by Gal(1-29) and Gal(2-11) (10nmol, IT).
      These findings suggest that the antihyperalgesic effect of spinal galanin is due
      to its action on sites both presynaptic (inhibition of SP release) and
      postsynaptic (blockade of SP-evoked hyperalgesia and PGE2 production) to the
      primary afferents.

PMID- 15944015
TI  - Increased hyperalgesia after tissue injury and faster recovery of allodynia after
      nerve injury in the GalR1 knockout mice.
AB  - Evidence suggests that galanin and its receptors including GalR1 are involved in
      the modulation of nociception. To understand the contributions of this galanin
      receptor subtype to the analgesic effect of galanin, we systematically examined
      the nociception phenotype of the GalR1 knockout (KO) mice. (1) Baseline
      thresholds: Thermal escape latencies and tactile thresholds of the hind paws were
      not different between the GalR1 KO and wild type (WT) mice. (2) Thermal injury
      evoked hyperalgesia: Thermal injury (52 degrees C, 45 s) to one hind paw resulted
      in a reduction in the thermal escape latency as compared to the uninjured paw.
      The right/left difference score was significantly greater in the KO (5.9 +/- 0.8
      s) than for the WT (2.8 +/- 0.7 s) indicating a greater hyperalgesia. (3)
      Formalin-induced flinching: Formalin paw injection (2.5%/20 microl) produced a
      two-phase flinching in both GalR1 KO and WT groups, that was detected by an
      automated flinching sensor device. Phase II flinching of KO (1510 +/- 90) was
      slightly greater than that observed for WT (1290 +/- 126), but the difference is
      not statistically significant. (4) Nerve injury evoked allodynia: Tactile
      thresholds were assessed prior to and at intervals up to 21 days after left L5
      spinal nerve ligation and transection. In both GalR1 KO and WT mice, nerve injury
      caused thresholds to fall to 0.2-0.3g though 11 days. On days 14-21, GalR1 KO
      animals showed a significant recovery as compared to WT. In summary, GalR1 KO
      mice showed no difference from WT with respect to acute nociception, but showed a
      modest tendency towards increased hyperalgesia after tissue injury and
      inflammation. These results are consistent with a regulatory effect of galanin at
      GalR1 receptors on nociceptive processing.

PMID- 15944016
TI  - Galanin impairs performance on learning and memory tasks: findings from galanin
      transgenic and GAL-R1 knockout mice.
AB  - Galanin (GAL) impairs performance on cognitive tasks when administered centrally
      to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits
      on the probe trial of the Morris water maze spatial learning task, on the social
      transmission of food preference olfactory memory task, and on the trace cued fear
      conditioning emotional learning and memory task. Knockout mice deficient in the
      GAL-R1 receptor subtype were normal on most memory tasks, while showing a small
      deficit in trace cued fear conditioning, suggesting a selective role for the GAL
      R1 in aversive memories, and implicating other GAL receptor subtypes in spatial
      learning and olfactory social memory. The growing body of rodent literature
      implicating excess GAL in cognitive impairment is relevant to the overexpression
      of GAL in the basal forebrain during the progression of Alzheimer's disease.

PMID- 15944017
TI  - Medial septal galanin and acetylcholine: influence on hippocampal acetylcholine
      and spatial learning.
AB  - Neurochemical and behavioral studies in the rat have provided evidence for the
      view that galanin impairs learning via an inhibitory modulation of cholinergic
      neurons in the septohippocampal projection, believed to be important for learning
      and memory. To test this hypothesis, galanin was microinjected via a unilateral
      chronic cannula located in MS/dBB of rats. Infusion of galanin in the MS/dBB,
      which contains a high number of 125I-galanin binding sites, did not impair
      spatial acquisition or memory. On the contrary, spatial acquisition tended to be
      facilitated by 1 and 3 nmoles of galanin, while the 0.3 nmol dose had no effect.
      Intraseptal injections of scopolamine (10 microg/rat), a non-specific muscarinic
      antagonist, also failed to alter learning performance. In contrast, co-injections
      of galanin (3 nmol) and scopolamine (10 microg) resulted in a marked impairment
      of spatial acquisition. The effect of intraseptal galanin on basal acetylcholine
      release in the ventral hippocampus was examined by in vivo microdialysis and high
      performance liquid chromatography. Both galanin (3 nmol/rat) and scopolamine (10
      microg/rat) infused into the MS/dBB increased basal acetylcholine release in the
      ventral hippocampus. The combined injections of galanin and scopolamine resulted
      in an excessive increase in acetylcholine release. These results indicate, that
      galanin activates septohippocampal cholinergic neurons, suggesting that septal
      galanin may have a facilitatory role in spatial learning. Moreover, the level of
      muscarinic activity within the septal area appears to be critical for the effects
      of galanin on cognitive functions, since the combination of galanin and
      scopolamine produced a marked impairment in spatial learning, despite a marked
      increase in hippocampal acetylcholine release. In summary, a limited range of
      cholinergic muscarinic transmission may contribute to optimal hippocampal
      function, a finding that has important implications for therapeutic approaches in
      the treatment of disorders of memory function.

PMID- 15944018
TI  - Effect of galnon on induction of long-term potentiation in dentate gyrus of
      C57BL/6 mice.
AB  - The impairment of cognitive performance by galanin administration in rodents
      indicates a possible modulating effect of this neuropeptide on long-term
      potentiation (LTP) induction in the hippocampal formation. Galnon is a non
      peptide, systemically active galanin receptor agonist which has been tested in
      feeding, seizure and forced swim task in in vivo rodent experimental models.
      Similarly to galanin (1-29) (i.c.v.), galnon (i.p.) has exhibited anticonvulsant
      effects in rats. We have investigated the effect of galnon on the synaptic
      transmission and plasticity in hippocampal dentate gyrus (DG) of C57Bl/6 mice and
      compared the galnon effects to the effect of galanin (1-29) and galmic, a non
      peptide galanin receptor agonist. Similarly to galanin (1-29) and galmic,
      superfusion of galnon did not alter the input-output responses in DG.
      Administration of galnon (1 microM) significantly attenuated the LTP induction by
      85.5 +/- 1% by 51 min after high frequency trains stimulation. This result was
      very similar to the effect of galanin (1-29) and galmic, which caused an 80 +/-
      1.5% and 94 +/- 2% reduction in the level of field potentiation, respectively.
      The PPF responses, however, were not altered due to galnon superfusion which is
      in contrast to the effect of galanin (1-29) or galmic. In summary, these data
      indicate that the systemically active, non-peptide galanin receptor agonist,
      galnon can exert similar effects to galanin (1-29) in attenuation of DG LTP in
      mice.

PMID- 15944019
TI  - Galanin in the hippocampal formation of female rats--effects of 17beta-estradiol.
AB  - 17Beta-estradiol induced an increase in tissue concentrations of galanin in the
      hippocampal formation of ovariectomized rats. This increase was dose- and time
      dependent, and occurred already 60 min after steroid administration and was not
      blocked by Tamoxifen). There was also an increase in galanin in the pro-estrous
      phase in regularly cycling rats. The estrogen-induced rapid increase may at least
      in part be due to decreased release of galanin as demonstrated by in vivo
      microdialysis studies. Thus, sex steroid hormones may influence signalling
      molecules in brain areas of importance for cognitive functions.

PMID- 15944020
TI  - Age-related impairments of synaptic plasticity in the lateral perforant path
      input to the dentate gyrus of galanin overexpressing mice.
AB  - In the present study, electrophysiological recordings were made from hippocampal
      slices obtained from mice overexpressing galanin under the promoter for the
      platelet-derived growth factor-B (GalOE mice). In these mice, a particularly
      strong galanin expression is seen in the granule cell layer/mossy fibers. Paired
      pulse facilitation (PPF) of excitatory postsynaptic field potentials (fEPSPs) at
      the lateral perforant path (LPP)-dentate gyrus synapses was elicited in the
      dentate gyrus after stimulation with different interpulse intervals. Slices from
      young adult wild-type (WT) animals showed significant PPF of the 2nd EPSP evoked
      with paired-pulse stimuli, while PPF was reduced in slices from young adult GalOE
      mice, as well as aged WT mice, but were not observed at all in slices from aged
      GalOE animals. Application of the putative galanin antagonist M35 increased PPF
      in slices from aged WT mice as well as from adult and aged GalOE mice, but had no
      effect in slices taken from young adult WT mice. These data indicate that galanin
      is involved in hippocampal synaptic plasticity, in particular in age-related
      reduction of synaptic plasticity in the LPP input to the dentate gyrus.
      Galaninergic mechanisms may therefore represent therapeutic targets for treatment
      of age-related memory deficits and Alzheimer's disease.

PMID- 15944021
TI  - Electrophysiological studies on galanin effects in brain--progress during the
      last six years.
AB  - The effects of galanin and galanin fragments have been studied on neurons in
      various brain regions of rodents using electrophysiological techniques. Here, we
      mainly review reports published during the last six years, that is after the
      second galanin symposium in 1998. These papers deal with locus coeruleus (LC),
      the hippocampal formation (HF), hypothalamus, the nucleus of the diagonal band of
      Broca (DBB) and the dorsal vagal complex (DVC). In most cases galanin has an
      inhibitory effect by increasing a potassium conductance or reducing a calcium
      conductance. In LC, beside a direct inhibitory effect, galanin exerts an indirect
      effect enhancing the noradrenaline-induced hyperpolarization. In the HF, galanin
      (1-15), but not galanin (1-29), induces hyperpolarization in CA3 pyramidal
      neurons. Inhibitory effects of galanin on several forms of synaptic plasticity
      including long-term potentiation, frequency facilitation and paired-pulse
      facilitation have also been demonstrated in normal and transgenic animals. In the
      hypothalamic arcuate nucleus galanin has a presynaptic action inhibiting
      glutamate release, as well as a postsynaptic effect via the galanin R1 receptor.
      In the DVC, galanin inhibits dorsal vagal motor neurons projecting to the stomach
      by activation of a postsynaptic galanin receptor. However, excitatory effects of
      galanin have also been reported in several regions, such as the DBB nucleus,
      where galanin increases excitability by decreasing a K+ conductance. Taken
      together, electrophysiological studies have further supported the role of galanin
      as a neurotransmitter/neuromodulator in the brain.

PMID- 15944022
TI  - Regulation of limbic status epilepticus by hippocampal galanin type 1 and type 2
      receptors.
AB  - It has been well established that galanin is a potent endogenous anticonvulsant
      peptide. However, the role of galanin receptor subtypes in mediating
      anticonvulsant effects of the peptide is poorly understood. Using
      pharmacological, transgenic and antisense approaches, we examined the involvement
      of galanin receptors GalR1 and GalR2 in regulating seizures and associated
      neuronal degenerative changes. In the rat model of status epilepticus (SE)
      induced by electrical stimulation of perforant path, in vivo uncoupling of G
      protein coupled receptors (GPCR) through intrahippocampal administration of
      pertussis toxin (PTX) facilitated the initiation of SE, and increased the
      severity of the established SE. Injection of a non-selective GalR1/GalR2 agonist
      galanin (1-29) and a preferential GalR2 agonist galanin (2-11) into the
      hippocampus of PTX-pretreated rats revealed that while during early phase of SE
      galanin inhibited seizures predominantly through GalR1, GalR2 mediated
      anticonvulsant effects of the peptide during advanced stage of SE. GalR1 knockout
      mice showed increased severity of both pilocarpine- and perforant path
      stimulation -induced SE, compared to wild type (WT) littermates. In GalR1
      knockout animals SE led to more severe and wider-spread hippocampal injury, than
      in WT. Focal downregulation of GalR2, which had been achieved in rats by
      intrahippocampal infusion of anti-GalR2 peptide nucleic acid (PNA) antisense,
      significantly increased the severity of perforant path stimulation- induced SE.
      Downregulation of GalR2 led to mild injury to hilar interneurons and potentiated
      seizure-induced hippocampal damage. In conclusion, both GalR1 and GalR2 mediate
      anticonvulsant effects of galanin. GalR1 and GalR2 exhibit differential effects
      on the initiation and the maintenance phases of SE. Activation of both galanin
      receptor subtypes exerts neuroprotective effects under conditions of excitotoxic
      injury.

PMID- 15944023
TI  - Testing the hypothesis that locus coeruleus hyperactivity produces depression
      related changes via galanin.
AB  - This paper reviews progress made in testing the idea that depression-related
      behavioral changes can arise from hyperactivity of locus coeruleus (LC) neurons
      which consequently inhibits activity of mesocorticolimbic dopamine neurons in the
      ventral tegmentum (VTA) via release of galanin from terminals on LC axons in VTA.
      Results from pre-clinical testing are described, including the most recent
      findings indicating that, in an animal model that shows long-lasting symptoms of
      depression, recovery to normal activity in the home cage is accelerated by
      infusion of a galanin receptor antagonist, galantide (M15), into VTA. Data are
      also described suggesting that all effective antidepressant treatments decrease
      activity of LC neurons.

PMID- 15944024
TI  - One for all or one for one: does co-transmission unify the concept of a brain
      galanin "system" or clarify any consistent role in anxiety?
AB  - Galanin (GAL) is a potential target for novel antidepressant or anti-anxiety drug
      development. However, no integrated role for a "brain galanin system" in anxiety
      has yet emerged. It is possible that such a function may be revealed by examining
      the interaction of GAL with norepinephrine (NE), with which it is prominently co
      localized. We showed previously that enhancing stress-activation of the NE system
      by yohimbine (YOH) pretreatment induced the release of GAL in central amygdala
      (CeA) to exert an anxiolytic effect on the elevated plus-maze. However, it
      remained to be demonstrated conclusively that GAL was co-released from NE
      terminals in CeA in this context, or if a multi-synaptic circuit activated GAL
      release from another afferent to CeA, or from local GAL neurons in the vicinity
      of CeA. In studies presented at the Third International Symposium on Galanin and
      Its Receptors, we utilized a combination of behavioral pharmacological
      approaches, testing the effects of YOH on the behavioral response to stress on
      the plus-maze after lesioning NE afferents to CeA with 6-OHDA, and anatomical
      approaches to identify GAL afferents to CeA that are activated in the context of
      stress with yohimbine pretreatment, to address these alternatives. Our results
      suggest that GAL was not co-released from noradrenergic terminals innervating CeA
      to exert an anxiolytic influence when noradrenergic activation was amplified by
      yohimbine pretreatment. Rather, it most likely originated from GAL neurons
      immediately adjacent to CeA that were activated by a non-noradrenergic afferent
      arising from elsewhere in the brain, itself activated by increasing NE activity.
      Thus, any role for brain GAL in anxiety remains region-specific, pathway
      specific, response specific and context-specific, which is likely to continue to
      present challenges to the development of novel agents targeting brain GAL for
      treatment of depression or anxiety.

PMID- 15944025
TI  - Distribution of galanin in the brain of a galanin-overexpressing transgenic
      mouse.
AB  - The distribution of galanin mRNA-expressing cells and galanin-immunoreactive (IR)
      cell bodies and processes was studied in the brain of mice overexpressing galanin
      under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in
      colchicine-treated and non-treated animals. A widespread ectopic expression of
      galanin (both mRNA and peptide) was found, that is when neither transcript nor
      peptide could be seen in WT mice, not even after colchicine treatment. However,
      in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal
      cells, and Purkinje cells only galanin mRNA could be detected. The highest levels
      of galanin expression were observed in the forebrain structures (the mitral cells
      of the olfactory bulb, throughout the cortex, granular and pyramidal cell layers
      of the hippocampus), in the mesencephalon (nucleus ruber), in the cerebellum
      (lateral cerebellar nucleus), in the pons (sensory and motor nuclei of the
      trigeminal nerve), within the medulla oblongata (facial, prepositus and spinal
      trigeminal nuclei). High densities of galanin-IR fibers were found in the axonal
      terminals of the lateral olfactory tract, hippocampal and presumably cerebellar
      mossy fiber system, in several thalamic and hypothalamic regions and the lower
      brain stem.

PMID- 15944026
TI  - Behavioural characterisation of transgenic mice overexpressing galanin under the
      PDGF-B promoter.
AB  - The behavioural phenotype of transgenic mice (3-5-months old) overexpressing
      galanin (GalOE mice) under the platelet-derived growth factor B (PDGF-B) promoter
      was evaluated in a battery of tests, including locomotor cages, light-dark
      exploration test, elevated plus-maze and the Porsolt forced swim test. Learning
      and memory were assessed in the Morris water maze task. GalOE mice showed a
      slight increase in spontaneous locomotor activity assessed in the locomotor
      cages, but the amphetamine-induced increase in locomotor activity was somewhat
      lower in GalOE mice. Anxiety-like behaviour in light-dark exploration and
      elevated plus-maze tests did not differ between genotypes. In the Porsolt forced
      swim test, GalOE mice displayed an increased time of immobility, indicative of
      increased learned helplessness possibly reflecting increased stress
      susceptibility and/or depression-like behaviour. GalOE mice showed normal
      learning and memory retention in the Morris water maze tasks. These data support
      the hypothesis that galanin may have a role in functions related to mood states,
      including affective disorders.

PMID- 15944027
TI  - Behavioral and neurochemical studies on brain aging in galanin overexpressing
      mice.
AB  - To study possible involvement of galanin in brain aging quality, we have
      investigated behavioral, neurochemical and morphological parameters in aged mice
      overexpressing galanin under the platelet-derived growth factor B promoter (GalOE
      mice) compared to wild-type littermates (WT mice). The behavioral analysis in the
      forced swim test showed that old GalOE animals spent more time in immobility
      compared to WT. In the activity cage test, galanin overexpression counteracted
      the age-induced decrease in exploratory behavior. The neurochemical analysis
      showed a 30% decrease in noradrenaline overflow in the cerebral cortex of WT old
      mice that was not present in age-matched GalOE mice. Our results indicate that
      overexpression of galanin can influence several behavioral and neurochemical
      parameters in old mice.

PMID- 15944028
TI  - Galanin can attenuate opiate reinforcement and withdrawal.
AB  - Galanin and its receptors are expressed in brain areas associated with opiate
      reinforcement and withdrawal. An emerging body of data suggests that galanin can
      attenuate the neurochemical, physiological and behavioral signs of opiate
      reinforcement and withdrawal. Experiments in transgenic mice overexpressing
      galanin and knockout mice lacking the peptide support a role for endogenous
      galanin in modulating the actions of opiates on brain regions associated with
      reinforcement and withdrawal. These studies suggest that galanin receptor
      agonists could be useful therapeutic agents to combat opiate addiction. Further,
      genetic variation in the genes encoding galanin and its receptors could be
      associated with altered susceptibility to opiate dependence.

PMID- 15944029
TI  - Assessment of new functional roles for galanin in the CNS.
AB  - There is considerable evidence that galanin plays an important role in food
      intake, nociception, stress reactivity, sexual behavior, and learning. However,
      its involvement in other important behavioral processes, especially higher
      cognition, has not been systematically investigated. This review summarizes our
      recent efforts to explore the role of galanin in executive processes as well as
      in fundamental motivational and motor productive processes that are essential to
      the behavioral assessment of cognitive constructs in rodents. Our work points to
      a role in reward processes and physiological water balance regulation, and argues
      against a role for galanin in fine motor production and maintenance, simple
      visual discrimination, and perseveration.

PMID- 15944030
TI  - Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol
      ingestion, circulating lipids and energy homeostasis.
AB  - Galanin (GAL) is known to stimulate feeding behavior. This peptide has different
      properties and functions from other feeding stimulants, e.g., neuropeptide Y and
      agouti-related protein. Hypothalamic GAL is relatively unresponsive to food
      deprivation and to changes in corticosterone, glucose utilization, dietary
      carbohydrate and leptin. This indicates that this peptide is not essential under
      conditions when food is scarce or low-energy, high-carbohydrate diets are being
      consumed. In contrast, recent evidence suggests that GAL in the paraventricular
      nucleus (PVN) functions in close relation to dietary fat and alcohol. In
      particular, it mediates functions that allow animals to adapt to conditions of
      positive energy balance involving excess consumption of these nutrients. This
      peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is
      stimulated by an increase in circulating lipids caused by a fat-rich meal or
      alcohol consumption, and it rises during the middle of the active feeding cycle,
      when fat consumption and triglycerides naturally rise. When centrally injected,
      GAL in the PVN increases the consumption of food and alcohol. Moreover, it
      produces a significantly stronger feeding response in rats maintained on a fat
      rich diet, which also promotes alcohol intake. This evidence supports the
      existence of non-homeostatic, positive feedback circuits between GAL and both
      dietary fat and alcohol. These circuits are believed to contribute to the large
      meal size, over-consumption of alcohol, and obesity which are generally
      associated with fat-rich foods.

PMID- 15944031
TI  - Exaggerated feeding response to central galanin-like peptide administration in
      diet-induced obese rats.
AB  - Galanin-like peptide (GALP) is a newly identified neuropeptide implicated in the
      regulation of metabolism and reproduction. GALP gene expression is decreased in
      the hypothalamus of genetically obese rodents, such as fa/fa rats and ob/ob mice,
      and central administration of GALP increases feeding in satiated rats. The effect
      of dietary obesity on GALP-induced feeding is unknown, so this study
      characterized the effects of central administration of GALP on feeding in a rat
      model of diet-induced obesity. Male Sprague-Dawley rats (n = 21) were randomly
      assigned to receive standard laboratory chow (12% fat as kcal) or high-fat
      cafeteria diet (35% fat) for 12 weeks before intracerebroventricular (icv)
      cannulae were implanted. Seven days later, rats received 0,0.2 or 0.3 nmol doses
      of GALP in randomized order at least 48 h apart. Food intake was measured at
      0.5,1,2, 4 and 24 h post administration and body weight was measured at 24 h.
      Rats were maintained on their respective diets throughout the entire feeding
      experiment. Implementation of the high-fat diet led to significantly greater
      caloric intake (230%) and body weight (28%) compared to chow-fed control rats.
      GALP-induced feeding was rapid and maximal in both dietary groups at 30 min post
      injection. The 0.3 nmol dose of GALP led to significantly larger increases in
      caloric intake in high-fat fed rats than in chow-fed controls (35.4 +/- 3.7 and
      22.1 +/- 1.3 kcal, respectively, at 30 min). It is not known if diet-induced
      obesity alters endogenous GALP levels, but our data suggest that adaptive
      responses in GALP signaling might occur during chronic overfeeding. One possible
      explanation is an increased sensitivity and/or number of specific GALP receptors,
      although actions of exogenous GALP may also represent pharmacological actions at
      galanin receptors.

PMID- 15944032
TI  - Galanin in human plasma.
AB  - The neuropeptide galanin has important effects on hormone secretion from the
      hypothalamus and pituitary, and it may also be involved in central biological
      processes such as pain, memory, and food intake. Yet, there is limited knowledge
      about how these processes are reflected by circulating galanin. To study the
      levels and molecular forms of galanin in the human circulation, plasma was
      analysed from 26 healthy subjects, 14 women and 12 men, using two extraction
      methods and a specific radioimmunoassay for human galanin. Galanin-LI levels in
      unextracted plasma were higher (141-191 pmol/L) than after immunoextraction (3.4
      30.7 pmol/L) and Sep Pak extraction (2.2-12.6 pmol/L). Galanin immunoreactivity
      after Sep Pak and immunoextraction correlated (r = 0.74, p<0.001). Galanin-LI
      levels were significantly higher in the men than in the women (p = 0.01) after
      Sep Pak extraction. A small increase in galanin-LI was seen with age in the women
      (r = 0.54, p < 0.05). The proportion of Sep Pak extracted galanin-LI increased
      with age in the women (r = 0.73, p < 0.05)) but not in the men.

PMID- 15944033
TI  - Galanin modulates cholinergic neurotransmission in the heart.
AB  - The role of galanin (Gal) in the modulation of cholinergic neurotransmission in
      the heart in wild-type (129 SvJ), and GALR1 knockout mice has been studied. The
      mice were anaesthetised and ventilated. Blood pressure (BP) and the increase in
      pulse interval evoked by stimulation of the vagus nerve (deltaPI) were recorded.
      Resting BP and PI were not different in control and GALR1-KO mice. In control
      mice an intravenous, bolus injection of Gal (0.8-13 nmol/kg; n = 4-6) attenuated
      the deltaPI, dose dependently from 33 +/- 7% to 78 +/- 9.5%. In GALR1-KO mice,
      Gal (0.8-13 nmol/kg) did not attenuate deltaPI at any dose (n = 3-4). In control
      mice intravenous, bolus injection of neuropeptide Y (NPY; 0.5-10 nmol/kg, n = 5
      7) attenuated the deltaPI by 13 +/- 10% to 67 +/- 7% with a half time to recovery
      of 0.5-5 +/- 1 min. In control mice, following activation of the cardiac
      sympathetic nerve (10 Hz for 2 min; n = 3) the deltaPI was attenuated by 92 +/-
      2% with a half time to recovery of 7 +/- 1 min. In control mice in the presence
      of the beta-adrenoceptor antagonist propranolol (1 mg/kg), and 1 micromol/kg
      BIIE0426 (an NPY Y2 receptor antagonist) the deltaPI was 57+/-3% with a half time
      to recovery of 2.5+/-0.5 min. In GALR1-KO mice, in the presence of propranolol
      and BIIE0426 there was no inhibition of deltaPI. In mice, it is proposed that
      both Gal and NPY contribute to the prolonged attenuation of parasympathetic
      slowing of the heart following activation of the cardiac sympathetic nerve.

PMID- 15944034
TI  - Galanin and galanin receptors in human cancers.
AB  - The increasing interest in peptides and peptide receptors in cancer is based on
      the possibility of receptor targeting, because peptide receptors are often
      expressed in different human tumors. The neuropeptide galanin has also been
      suggested to be involved in the development of neuroendocrine tumors based on the
      development of estrogen-induced tumors in estrogen-sensitive rats. This study
      summarizes our current knowledge on the expression of galanin peptide and galanin
      receptors in different human neuroendocrine tumors. The expression of both,
      peptide and corresponding receptor, seems to be a common feature of human
      gliomas, pheochromocytomas, pituitary and neuroblastic tumors. The co-expression
      of galanin and its receptors supports a role for galanin in tumor cell pathology
      via autocrine/paracrine mechanisms.

PMID- 15944036
TI  - The United Kingdom Acid Waters Monitoring Network: a review of the first 15 years
      and introduction to the special issue.
AB  - The United Kingdom Acid Waters Monitoring Network (AWMN) was established in 1988
      to determine the ecological impact of acidic emissions control policy on acid
      sensitive lakes and streams. AWMN data have been used to explore a range of
      causal linkages necessary to connect changes in emissions to chemical and,
      ultimately, biological recovery. Regional scale reductions in sulphur (S)
      deposition have been found to have had an immediate influence on surface water
      chemistry, including increases in acid neutralising capacity, pH and alkalinity
      and declines in aluminium toxicity. These in turn can be linked to changes in the
      aquatic biota which are consistent with "recovery" responses. A continuation of
      the current programme is essential in order to better understand apparent non
      linearity between nitrogen (N) in deposition and runoff, the substantial rise in
      organic acid concentrations, and the likely impacts of forecast climate change
      and other potential constraints on further biological improvement.

PMID- 15944037
TI  - Changes in the atmospheric deposition of acidifying compounds in the UK between
      1986 and 2001.
AB  - Emissions of a precursor of acidity in precipitation, sulphur dioxide (SO2),
      declined in the UK and the EU (15) by 71% and 72%, respectively, between 1986 and
      2001, while nitrous oxide emissions declined by about 40%. Acidity in UK
      precipitation and the deposition of sulphate in precipitation halved during this
      period, but reductions were larger in the English Midlands than at the west coast
      and in high rainfall areas (>2000 mm). There is evidence that the smaller
      reductions in sulphur deposition in the west and south are due in part to
      shipping sources of SO2. Reductions in sulphur dry deposition (74%) are larger
      than in wet deposition (45%), due to changes in the canopy resistance to dry
      deposition. For reduced nitrogen, there has been a small (10%) reduction in
      emissions and deposition, while for oxidized nitrogen, a substantial reduction in
      emissions (40%) occurred but wet deposition of nitrate changed by less than 10%.

PMID- 15944038
TI  - Trends in surface water chemistry of acidified UK freshwaters, 1988-2002.
AB  - Analysis of water chemistry data from 15 years of monitoring at 22 acid-sensitive
      lakes and streams in the UK reveals coherent national chemical trends indicative
      of recovery from acidification. Excess sulphate and base cations exhibit
      significant decline, often accompanied by an increase in an alkalinity-based
      determination of acid neutralising capacity (AB-ANC) and, at fewer sites, a
      decline in hydrogen and labile aluminium. Acid neutralising capacity determined
      by "charge-balance" (CB-ANC) exhibits few trends, possibly due to compound errors
      associated with its determination. Trend slopes in excess sulphate correlate with
      those for base cations, hydrogen ion and AB-ANC, with between-site variability
      linked to catchment hydrology, sea-salt inputs and forestry. Nitrate
      concentrations have not changed significantly but show high sensitivity to
      varying climate. Trends in AB-ANC are influenced by significant increases in
      dissolved organic carbon, the cause of which it is vital to establish before
      trends in the former can definitively be attributed to decreasing acidic
      deposition.

PMID- 15944039
TI  - Evidence of sulphur and nitrogen deposition signals at the United Kingdom Acid
      Waters Monitoring Network sites.
AB  - Some recent studies of trends in sulphate in surface waters have alluded to
      possible lag effects imposed by catchment soils, resulting in discrepancies
      between trends in deposition and run-off. To assess the extent of these possible
      effects in the UK, sulphate concentration data from the United Kingdom Acid
      Waters Monitoring Network (AWMN) sites are compared with estimates of sulphur
      deposition at each site. From these data, input-output budgets are computed at an
      annual time scale. The estimated budgets suggest a close association between
      catchment sulphur inputs and outputs at an annual scale, with well-balanced
      annual budgets at most sites, indicative of only minor lag effects. A similar
      analysis of the AWMN site nitrogen budget shows little evidence of an association
      between nitrogen inputs and outputs at this time scale.

PMID- 15944040
TI  - Long-term increases in surface water dissolved organic carbon: observations,
      possible causes and environmental impacts.
AB  - Dissolved organic carbon (DOC) concentrations in 22 UK upland waters have
      increased by an average of 91% during the last 15 years. Increases have also
      occurred elsewhere in the UK, northern Europe and North America. A range of
      potential drivers of these trends are considered, including temperature,
      rainfall, acid deposition, land-use, nitrogen and CO2 enrichment. From
      examination of recent environmental changes, spatial patterns in observed trends,
      and analysis of time series, it is suggested that DOC may be increasing in
      response to a combination of declining acid deposition and rising temperatures;
      however it is difficult to isolate mechanisms based on monitoring data alone.
      Long-term DOC increases may have wide-ranging impacts on freshwater biota,
      drinking water quality, coastal marine ecosystems and upland carbon balances.
      Full understanding of the significance of these increases requires further
      knowledge of the extent of natural long-term variability, and of the natural
      "reference" state of these systems.

PMID- 15944041
TI  - Nitrate leaching as a confounding factor in chemical recovery from acidification
      in UK upland waters.
AB  - Over the period 1988-2002, data from 18 of the 22 lakes and streams in the UK
      Acid Waters Monitoring Network (AWMN) show clear trends of declining excess
      sulphate concentrations in response to reductions in sulphur deposition, but
      fewer trends in increasing pH or alkalinity. There has been no significant
      decline in the deposition of total nitrogen over the same period, and no sites
      show a trend in nitrate concentration. Peak nitrate concentrations have already
      surpassed excess sulphate on occasion in half of the AWMN sites. Furthermore,
      current understanding of terrestrial N saturation processes suggests that nitrate
      leaching from soils may increase, even under a constant N deposition load. Best
      case projections indicate that nitrate will overtake sulphate as the major excess
      acid anion in many sites within 10 years, while worst-case predictions with
      steady-state models suggest that in the longer-term, nitrate could become the
      dominant excess acid anion in most of the UK.

PMID- 15944042
TI  - Biological responses to the chemical recovery of acidified fresh waters in the
      UK.
AB  - We report biological changes at several UK Acid Waters Monitoring Network lakes
      and streams that are spatially consistent with the recovery of water chemistry
      induced by reductions in acid deposition. These include trends toward more acid
      sensitive epilithic diatom and macroinvertebrate assemblages, an increasing
      proportional abundance of macroinvertebrate predators, an increasing occurrence
      of acid-sensitive aquatic macrophyte species, and the recent appearance of
      juvenile (<1 year old) brown trout in some of the more acidic flowing waters.
      Changes are often shown to be directly linked to annual variations in acidity.
      Although indicative of biological improvement in response to improving water
      chemistry, "recovery" in most cases is modest and very gradual. While specific
      ecological recovery endpoints are uncertain, it is likely that physical and
      biotic interactions are influencing the rate of recovery of certain groups of
      organisms at particular sites.

PMID- 15944043
TI  - The ecology of acidification and recovery: changes in herbivore-algal food web
      linkages across a stream pH gradient.
AB  - We examined the effects of acidification on herbivore-algal food web linkages in
      headwater streams. We determined the structure and abundance of consumer and
      benthic algal assemblages, and gauged herbivory, in 10 streams along a pH
      gradient (mean annual pH 4.6-6.4). Biofilm taxonomic composition changed with pH
      but total abundance did not vary systematically across the gradient. Mayflies and
      chironomids dominated under circumneutral conditions but declined with increasing
      acidity and their consumption of algae was strongly reduced. Contrary to
      expectations, several putative shredder species consumed algae, maintaining the
      herbivore-algal linkage where specialist grazers could not persist. These shifts
      in functioning could render the communities of acidified streams resistant to
      reinvasion when acidity ameliorates and water chemistry is restored to a pre
      acidification condition. This hypothesis is discussed in the light of recent
      trends in the chemistry and biology of the UK Acid Waters Monitoring Network
      sites.

PMID- 15944044
TI  - Defining reference conditions for acidified waters using a modern analogue
      approach.
AB  - Analogue matching is a palaeolimnological technique that aims to find matches for
      fossil sediment samples from a set of modern surface sediment samples. Modern
      analogues were identified that closely matched the pre-disturbance conditions of
      eight of the UK Acid Waters Monitoring Network (AWMN) lakes using diatom- and
      cladoceran-based analogue matching. These analogue sites were assessed in terms
      of hydrochemistry, aquatic macrophytes and macro-invertebrates as to their
      suitability for defining wider hydrochemical and biological reference conditions
      for acidified sites within the AWMN. The analogues identified for individual AWMN
      sites show a close degree of similarity in terms of their hydrochemical
      characteristics, aquatic macrophytes and, to a lesser extent, macro-invertebrate
      fauna. The reference conditions of acidified AWMN sites are inferred to be less
      acidic than today and to support a wider range of acid-sensitive aquatic
      macrophyte and macro-invertebrate taxa than that recorded in the AWMN lakes over
      the period of monitoring since 1988.

PMID- 15944045
TI  - Reconstructing pre-acidification pH for an acidified Scottish loch: a comparison
      of palaeolimnological and modelling approaches.
AB  - We reconstruct the pre-acidification pH of the Round Loch of Glenhead for 1800 AD
      using three diatom-pH transfer functions and a diatom-cladocera modern analogue
      technique (MAT), and compare these palaeo-data with hindcast data for the loch
      using the dynamic catchment acidification model MAGIC. We assess the accuracy of
      the transfer functions by comparing pH inferences from contemporary sediment and
      sediment trap diatom samples from the lake with measured pH from the UK Acid
      Waters Monitoring Network. The results from the transfer functions estimate the
      pH in 1800 to have been between 5.5. and 5.7, the MAT approach estimates pH at
      5.8 and the MAGIC hindcast (for 1850) is pH 6.1. Whilst we have no independent
      method of assessing which of these values is most accurate, the disagreement
      between the two approaches indicates that further work is needed to resolve the
      discrepancies.

PMID- 15944046
TI  - Temporal trends in spheroidal carbonaceous particle deposition derived from
      annual sediment traps and lake sediment cores and their relationship with non
      marine sulphate.
AB  - Spheroidal carbonaceous particles (SCPs) provide an unambiguous indication of
      atmospherically deposited contamination from industrial sources. SCP data from a
      12 year annual sediment trapping and coring programme at 14 lakes based on the UK
      Acid Waters Monitoring Network, were used to consider temporal trends in
      deposition and to compare these with measured non-marine sulphate fluxes. Results
      show good temporal coherence across a broad area of northern UK and that SCP
      deposition levels and are now at their lowest since the 1940s, in agreement with
      modelled sulphate data. SCP fluxes show reasonable linearity with measured non
      marine sulphate depositional fluxes from the nearest UK Acid Deposition
      Monitoring Network sites, especially over the post-flue-gas desulphurisation
      period, but comparisons prior to 1972 are not possible due to lack of data. We
      speculate on whether palaeolimnological SCP data might be used to reconstruct the
      history of non-marine sulphate fluxes from industrial sources.

PMID- 15944047
TI  - Regional scale evidence for improvements in surface water chemistry 1990-2001.
AB  - The main aim of the international UNECE monitoring program ICP Waters under the
      Convention of Long-range Transboundary Air Pollution (CLRTAP) is to assess, on a
      regional basis, the degree and geographical extent of the impact of atmospheric
      pollution, in particular acidification, on surface waters. Regional trends are
      calculated for 12 geographical regions in Europe and North America, comprising
      189 surface waters sites. From 1990-2001 sulphate concentrations decreased in all
      but one of the investigated regions. Nitrate increased in only one region, and
      decreased in three North American regions. Improvements in alkalinity and pH are
      widely observed. Results from the ICP Waters programme clearly show widespread
      improvement in surface water acid-base chemistry, in response to emissions
      controls programs and decreasing acidic deposition. Limited site-specific
      biological data suggest that continued improvement in the chemical status of acid
      sensitive lakes and streams will lead to biological recovery in the future.

PMID- 15944048
TI  - Prophylactic antibiotics for preventing early Gram-positive central venous
      catheter infections in oncology patients, a Cochrane systematic review.
AB  - OBJECTIVE: Long-term tunnelled central venous catheters (TCVC) are increasingly
      used in oncology patients. Infections are a frequent complication of TCVC, mostly
      caused by Gram-positive bacteria. The objective of this review is to evaluate the
      efficacy of antibiotics in the prevention of early Gram-positive TCVC infections,
      in oncology patients. DATA SOURCES: We searched MEDLINE, EMBASE, and the Cochrane
      Controlled Trials Register up to July 2003. REVIEW METHODS: We selected
      randomised controlled trials (RCT) evaluating prophylactic antibiotics prior to
      insertion of the TCVC, and the combination of an antibiotic and heparin to flush
      the TCVC, in paediatric and adult oncology patients. The primary outcome was
      documented Gram-positive bacteraemia in patients with a TCVC. All trials
      identified were assessed and the data extracted independently by two reviewers.
      RESULTS: There were nine trials included. Four trials reported on
      vancomycin/teicoplanin prior to insertion of the TCVC compared to no antibiotics.
      There was no reduction in the number of Gram-positive TCVC infections with an
      Odds ratio of 0.42 (95% confidence interval 0.13-1.31). Five trials studied
      flushing of the TCVC with a vancomycin/heparin solution compared to heparin
      flushing only. This method decreased the number of TCVC infections significantly
      with an Odds ratio of 0.43 (95% CI 0.21-0.87). CONCLUSION: Flushing the TCVC with
      a vancomycin/heparin solution reduced the incidence of Gram-positive infections.

PMID- 15944049
TI  - Salvage, dose intense and high-dose chemotherapy for the treatment of poor
      prognosis or recurrent germ cell tumours.
AB  - Most patients with metastatic testicular cancer are cured with cisplatin-based
      chemotherapy regimens. However, about 20-30% of patients with poor-risk germ cell
      tumours either fail to respond adequately or relapse after initial complete
      response. In an attempt to improve the treatment results, several phase II
      studies of high-dose chemotherapy (HDCT) and haematopoeitic stem cell support
      were performed initially in refractory or heavily pre-treated patients with germ
      cell tumours (GCT). Long-term disease-free survival (DFS) has been reported in
      nearly 13% (range 0-35%) of the patients in this group. Subsequently, HDCT trials
      have been conducted in first relapse; long-term DFS has been seen in 45% of the
      patients in these trials (range 21-67%). HDCT has also been evaluated in the
      first-line treatment of poor-risk GCTs; long-term DFS was achieved in 52% of the
      patients in this group (range 36-84%). Despite these encouraging results, a
      French randomised trial has failed to demonstrate any advantage of HDCT in the
      first-line treatment of poor-risk GCTs and thus the place of HDCT in routine
      practice remains uncertain. A number of randomised trials of HDCT are currently
      ongoing in the United States and Europe to better define the role of HDCT in this
      disease.

PMID- 15944050
TI  - Relevance of high-dose chemotherapy in solid tumours.
AB  - Drug resistance is a major problem in the treatment of solid tumours. Based on a
      steep dose-response relationship for especially alkylating agents on tumour cell
      survival, high-dose chemotherapy was considered of interest for the treatment of
      solid tumours. Results of phase 1 and 2 studies with high-dose chemotherapy in a
      variety of tumour types showed good response rates. Nowadays, several phase 3
      studies are available especially in metastatic and high-risk breast cancer
      patients. The high expectations of high-dose chemotherapy did not come true. This
      review analyses results of randomised studies and comments on the discrepancy
      between findings in patients versus those in tissue culture. Potential factors
      involved are the presence of tumour stem cells with different characteristics
      from more mature tumour cells, limitations in drug escalation in the clinic,
      transplant mortality, trial design and tumour cell contamination of the
      haematopoietic stem cell transplant. Maturation of the results from recent
      studies indicating a more modest benefit in, e.g., adjuvant breast cancer
      balanced versus long-term side effects will ultimately determine the role of high
      dose chemotherapy in certain solid tumours. In case of well-defined indications
      for high-dose chemotherapy, further selection of patients based on patient and
      tumour characteristics as well as the introduction of new agents will most likely
      play a role.

PMID- 15944052
TI  - Review: The physiology of saliva and transfer of drugs into saliva.
AB  - Although saliva or oral fluid "lacks the drama of blood, the sincerity of sweat
      and the emotional appeal of tears", quoting Mandel in 1990 [I.D. Mandel, The
      diagnostic uses of saliva, J. Oral Pathol. Med. 19 (1990) 119-125], it is now
      meeting the demand for inexpensive, non-invasive and easy-to-use diagnostic aids
      for oral and systemic diseases, drug monitoring and detection of illicit use of
      drugs of abuse, including alcohol. As the salivary secretion is a reflex response
      controlled by both parasympathetic and sympathetic secretomotor nerves, it can be
      influenced by several stimuli. Moreover, patients taking medication which
      influences either the central nervous system or the peripheral nervous system, or
      medication which mimic the latter as a side effect, will have an altered salivary
      composition and salivary volume. Patients suffering from certain systemic
      diseases may present the same salivary alterations. The circadian rhythm
      determines both the volume of saliva that will and can be secreted and the
      salivary electrolyte concentrations. Dietary influences and the patient's age
      also have an impact on composition and volume of saliva. The latter implies a
      wide variation in composition both inter- and intra-individually. Sampling must
      therefore be performed under standardized conditions. The greatest advantage,
      when compared to blood sample collection, is that saliva is readily accessible
      and collectible. Consequently, it can be used in clinically difficult situations,
      such as in children, handicapped and anxious patients, where blood sampling could
      be a difficult act to perform.

PMID- 15944053
TI  - Review: Pharmacokinetics of illicit drugs in oral fluid.
AB  - This article reviews studies that have measured drug concentrations in oral fluid
      following controlled dosing regimens. A total of 23 studies have been identified
      over the last 15 years. These show that the amphetamines including designer
      amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid
      following dosing and usually have similar time-courses to that in plasma.
      Following common doses peak oral fluid concentrations exceed 0.1 microg/mL and
      often even 1 microg/mL. The drug concentration will depend on whether a dilution
      step occurs with buffer as part of the sampling procedure. The uses of collectors
      that stimulate oral fluid usually reduce the drug concentration compared to a non
      stimulated manner. This reduction will not disadvantage the recipient since it
      will potentially reduce the detectability of drug in oral fluid compared to non
      stimulated collections. Only one recent study has been reported for a
      benzodiazepine. This showed nanogram per milliliter concentrations for
      flunitrazepam. More studies are required for benzodiazepines and indeed for other
      drugs, particularly in multiple drug situations and where disease may affect the
      pharmacokinetics of drugs.

PMID- 15944054
TI  - Oral fluid testing for driving under the influence of drugs: history, recent
      progress and remaining challenges.
AB  - In recent years the demand for drug testing in oral fluid in cases of driving
      under the influence has been increasing. The main advantages of saliva/oral fluid
      are the possibility for non-medical personnel to collect it without embarrassment
      and a better correlation between presence of drugs in oral fluid and impairment.
      Several surveys have been performed since the 1980s using saliva, and researchers
      encountered problems related to insufficient sample volume and insufficient
      sensitivity of the analytical methods. Steady progress has been shown in sample
      collection, knowledge of toxicokinetics in oral fluid, reliability of on-site and
      laboratory-based immunoassays and confirmation methods. In a few countries,
      legislation was passed that allows the use of saliva as a matrix for screening or
      confirmation. Despite this progress, some more work needs to be done, principally
      in the areas of the sensitivity and reliability of on-site screening devices,
      particularly for cannabis and benzodiazepines, knowledge about passive
      contamination and more generalised proficiency testing before oral fluid testing
      for DUID will have the reliability needed to be used forensically.

PMID- 15944055
TI  - Legal issues in oral fluid testing.
AB  - The use of oral fluid for drugs of abuse testing has received increased attention
      with the availability of accurate methods for the collection and analysis of
      drugs in oral fluid specimens. Already used in the transportation and insurance
      industries, there is increasing interest in oral fluid drug testing in the
      workplace, schools, roadside driving under the influence of drugs, and criminal
      justice. Given that sanctions may accrue from positive test results, legal
      challenges are to be expected. However, with its established scientific base,
      demonstrated accuracy and reliability of collection and test methods, and current
      positive regulatory developments, it seems clear that the use of oral fluid as a
      specimen for drugs of abuse testing will be able to withstand judicial scrutiny.

PMID- 15944056
TI  - Proficiency testing (external quality assessment) of drug detection in oral
      fluid.
AB  - Eighteen external quality assessment (proficiency testing) samples were prepared
      from client specimens collected with the Intercept oral fluid collection device
      and by spiking drug-free oral fluid. Samples were circulated in pairs at
      quarterly intervals to 13 UK and USA based laboratories for analysis by a panel
      of OraSure micro-plate Intercept enzyme immunoassay kits and hyphenated mass
      spectrophotometric techniques. During the survey, there was a single case of non
      specificity in a false report for methadone. The major errors were of lack of
      sensitivity relative to the concentration thresholds specified for the
      immunoassays. The sensitivity for overall "present"/"not found" reports
      calculated as true positives/(true positives+false negatives) were for the
      amphetamine specific assay 50%, methyl-amphetamines 93%, barbiturates 64%,
      cannabinoids 73%, cocaine and metabolites 100%, benzodiazepines 69%, methadone
      95%, opiates 79% (opiates excluding oxycodone 93%), phencyclidine 93% and human
      gamma-globulin 97%. A small number of the sensitivity errors were attributable to
      errors in chromatographic confirmation techniques.

PMID- 15944057
TI  - Oral fluid drug tests: effects of adulterants and foodstuffs.
AB  - An on-site oral fluid drug screen, Oratect, was used to investigate the effects
      of adulterants and foodstuffs on oral fluid test results. Common foods,
      beverages, food ingredients, cosmetics and hygienic products were demonstrated
      not to cause false positive results when tested 30 min after their consumption.
      Evaluations of two commercial oral fluid adulterants, "Clear Choice Fizzy Flush"
      and "Test'in Spit n Kleen Mouthwash" suggest their mechanism of action is the
      clearing of residual drugs of abuse compounds through rinsing of the oral cavity.
      They do not directly destroy the drug compounds or change the pH of the oral
      fluid. It is also suggested that a common mouthwash would perform similar action.

PMID- 15944058
TI  - Drugs in injured drivers in Denmark.
AB  - As part of the project Impaired Motorists, Methods of Roadside Testing and
      Assessment for Licensing (IMMORTAL) under the European Commission's Transport RTD
      Programme of the 5th Framework Programme [I.M. Bernhoft, Drugs in accidents
      involved drivers in Denmark, D-R4.3 of the project Impaired Motorists, Methods Of
      Roadside Testing and Assessment for Licensing (IMMORTAL), , 2005], a study
      regarding drugs in accident-involved drivers was carried out in Denmark. The main
      objectives of this study were: (1) to collect and analyse samples from injured
      drivers for the presence of drugs; (2) to give an indication whether drugs may
      have contributed to traffic accidents; and (3) to get information on the drug
      positive drivers and their drug use. This paper focuses on objective 1. Injured
      drivers who were treated in hospital were asked to give a saliva sample, a blood
      sample or both. The samples were screened for the following substances: opiates,
      amphetamines, methamphetamines, incl. MDMA (ecstasy), cannabinoids and
      metabolites, cocaine and metabolites and benzodiazepines. Screenings were carried
      out by means of Cozart Microplate EIA kit. Positive screenings were confirmation
      analysed by gas chromatography-mass spectrometry (GC-MS) or liquid
      chromatography/tandem mass spectrometry (LC/MS/MS). In total, 26 out of 330
      patients were confirmed positive for one or more of the six drug groups. However,
      three patients were excluded from the survey for various reasons. Of the
      remaining 23 drug-positive patients 15 were found positive for one drug group,
      and in five of these cases alcohol was present in a concentration over the legal
      limit in Denmark (0.05%). The other eight patients were found positive for two
      drug groups, and in four of these cases, alcohol was also present in a
      concentration over the legal limit. Alcohol was found both in combinations with
      medicinal drugs, with illegal drugs and with both. Based on the saliva or blood
      concentrations, we estimate that there is a strong suspicion of impairment in 9
      out of 23 cases, and in another six cases it was likely that the drivers were
      impaired.

PMID- 15944059
TI  - Drugs in oral fluid Part I. Validation of an analytical procedure for licit and
      illicit drugs in oral fluid.
AB  - A qualitative and quantitative analytical method was developed and validated for
      the determination of 49 licit and illicit drugs in oral fluid. Small oral fluid
      samples, volume 1mL, were collected from volunteers using a modified Omni-Sal
      device and the analytes were extracted from an oral fluid/buffer mixture using a
      single Bond Elut Certify solid phase extraction cartridge. Liquid chromatography
      tandem mass spectrometry (LC-MS-MS) and gas chromatography-repetitive full scan
      mass spectrometry (GC-MS) were used in parallel to analyze the extracts for the
      targeted drugs. Extracts were analyzed by GC-MS in their underivatized form and
      as their pentafluoropropionyl derivatives. Deuterated internal standards were
      used for quantification of drugs of abuse by LC-MS-MS to minimize matrix effects.
      Methadone-d(9) and tumoxetine were used as the internal standards for
      quantification of non-derivatized and derivatized analytes respectively by GC-MS.
      Linearity was demonstrated over the range 5-200 ng/mL and limits of detection
      were less than 4 ng/mL for each drug analyzed. The method demonstrated acceptable
      recoveries for most of the analytes and good intra- and inter-day precision.
      Acquisition of data by repetitive full scan GC-MS allows the addition of further
      analytes to the target menu.

PMID- 15944060
TI  - Drugs in oral fluid Part II. Investigation of drugs in drivers.
AB  - As part of the European project, Impaired Motorists, Methods of Roadside Testing
      and Assessment for Licensing, otherwise known as IMMORTAL (Deliverable R4.2), the
      University of Glasgow was required to analyse 1396 oral fluid samples, collected
      from drivers, for a wide range of drugs. A previously described method to include
      49 drugs and metabolites was used. To include cannabis in the study a separate
      extraction method was required because of interferences caused by the collection
      device. The study group included drivers who were stopped at random and
      participation was entirely voluntary. The results showed that out of the 1396
      samples tested, 16.8% were positive for at least one drug. In the majority of
      positive cases (85%), monodrug use was found and the most commonly detected drug
      was 3,4-methylenedioxymethamphetamine. This study showed that a significant
      number of the driving population are positive for at least one drug.

PMID- 15944061
TI  - Analysis of Delta9-tetrahydrocannabinol in oral fluid samples using solid-phase
      extraction and high-performance liquid chromatography-electrospray ionization
      mass spectrometry.
AB  - An analytical method using solid-phase extraction (SPE) and high-performance
      liquid chromatography-mass spectrometry (LC-MS) has been developed and validated
      for the confirmation of Delta(9)-tetrahydrocannabinol (THC) in oral fluid
      samples. Oral fluid was extracted using Bond Elut LRC-Certify solid-phase
      extraction columns (10 cm(3), 300 mg) and elution performed with n-hexane/ethyl
      acetate. Quantitation made use of the selected ion-recording mode (SIR) using the
      most abundant characteristic ion [THC+H(+)], m/z 315.31 and the fragment ion, m/z
      193.13 for confirmation, and m/z 318.00 for the protonated internal standard,
      [d(3)-THC+H(+)]. The method proved to be precise for THC, in terms of both intra
      day and inter-day analyses, with coefficients of variation less than 10%, and the
      calculated extraction efficiencies for THC ranged from 76 to 83%. Calibration
      standards spiked with THC between 2 and 100 ng/mL showed a linear relationship
      (r(2)=0.999). The method presented was applied to the oral fluid samples taken
      from the volunteers during the largest music event in Portugal, named Rock in Rio
      Lisboa. Oral fluid was collected from 40 persons by expectoration and with
      Salivette. In 55% of the samples obtained by expectorating, THC was detected with
      concentration ranges from 1033 to 6552 ng/mL and in 45% of cases THC was detected
      at concentrations between 51 and 937 ng/mL. However, using Salivette collection,
      26 of the 40 cases had an undetectable THC.

PMID- 15944062
TI  - Screening and confirmatory method for benzodiazepines and hypnotics in oral fluid
      by LC-MS/MS.
AB  - A procedure is presented for the screening of 17 benzodiazepines and hypnotics in
      oral fluid after collection with the Intercept(R) device by LC-MS/MS (alprazolam,
      7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam, clobazam, diazepam,
      lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam, tetrazepam,
      triazolam, zaleplon, zopiclone and zolpidem). The method involves extraction of
      0.5 mL of oral fluid (previously stored in the Intercept blue buffer) treated
      with 0.5 mL of phosphate buffer (pH 8.4) in the presence of 5 ng diazepam-d(5)
      used as internal standard, with 3 mL of diethyl ether/methylene chloride (50/50)
      and separation using liquid chromatography-tandem mass spectrometry. The limits
      of quantification for all benzodiazepines and hypnotics range from 0.1 to 0.2
      ng/mL. Linearity is observed from the limit of quantification of each compound to
      20 ng/mL (r(2)>0.99). Coefficients of variation at 2 ng/mL, measured on 6 points
      range from 4 to 8% for all drugs, except zopiclone (34%). Extraction recovery,
      measured at the same concentration was higher than 90%. Ion suppression was
      evaluated for each compound and was lower than 10% for all drugs except zopiclone
      (93%). These results were found suitable to screen for 17 benzodiazepines in oral
      fluid and detect them at very low concentrations, making this method suitable for
      monitoring subjects under the influence.

PMID- 15944063
TI  - Determination of MDMA, MDA, MDEA and MBDB in oral fluid using high performance
      liquid chromatography with native fluorescence detection.
AB  - This paper describes the analytical methodology for the determination of MDMA,
      MDA, MDEA and MBDB in oral fluid. After a liquid-liquid extraction, the analysis
      was carried out by high performance liquid chromatography (HPLC), with
      fluorescence detection. The detector wavelength was fixed at 285 nm for
      excitation and 320 nm for emission. The mobile phase, a mixture of phosphate
      buffer (pH=5) and acetonitrile (75:25), and the column, Kromasil 100 C8 5 microm
      250 mm x 4.6mm, allowed good separation of the compounds in an isocratic mode in
      only 10 min. The method was validated and showed good limits of detection (2
      ng/mL) and quantitation (10 ng/mL) for all the amphetamine derivatives. No
      interfering substances were detected. A stability study of these compounds in
      oral fluid stored at three different temperatures (-18, 4 and 20 degrees C) over
      10 weeks was conducted, showing a time-dependent degradation of the four
      compounds.

PMID- 15944064
TI  - Quantitative analysis of multiple illicit drugs in preserved oral fluid by solid
      phase extraction and liquid chromatography-tandem mass spectrometry.
AB  - We present a validated method for the simultaneous analysis of basic drugs which
      comprises a sample clean-up step, using mixed-mode solid-phase extraction (SPE),
      followed by LC-MS/MS analysis. Deuterated analogues for all of the analytes of
      interest were used for quantitation. The applied HPLC gradient ensured the
      elution of all the drugs examined within 14 min and produced chromatographic
      peaks of acceptable symmetry. Selectivity of the method was achieved by a
      combination of retention time, and two precursor-product ion transitions for the
      non-deuterated analogues. Oral fluid was collected with the Intercept, a FDA
      approved sampling device that is used on a large scale in the US for workplace
      drug testing. However, this collection system contains some ingredients
      (stabilizers and preservatives) that can cause substantial interferences, e.g.
      ion suppression or enhancement during LC-MS/MS analysis, in the absence of
      suitable sample pre-treatment. The use of the SPE was demonstrated to be highly
      effective and led to significant decreases in the interferences. Extraction was
      found to be both reproducible and efficient with recoveries >76% for all of the
      analytes. Furthermore, the processed samples were demonstrated to be stable for
      48 h, except for cocaine and benzoylecgonine, where a slight negative trend was
      observed, but did not compromise the quantitation. In all cases the method was
      linear over the range investigated (2-200 microg/L) with an excellent intra-assay
      and inter-assay precision (coefficients of variation <10% in most cases) for QC
      samples spiked at a concentration of 4, 12 and 100 microg/L. Limits of
      quantitation were estimated to be at 2 microg/L with limits of detection ranging
      from 0.2 to 0.5 microg/L, which meets the requirements of SAMHSA for oral fluid
      testing in the workplace. The method was subsequently applied to the analysis of
      Intercept samples collected at the roadside by the police, and to determine MDMA
      and MDA levels in oral fluid samples from a controlled study.

PMID- 15944065
TI  - Evaluation of the Cozart RapiScan drug test system for opiates and cocaine in
      oral fluid.
AB  - The purpose of this study was to evaluate the efficiency of the Cozart RapiScan
      (CRS) drug test system for detecting opiates and cocaine in oral fluid. Oral
      fluid samples were collected using the Cozart RapiScan collection system from 358
      donors who were receiving treatment for their addiction and were monitored for
      drug misuse. A further 103 oral fluid samples were collected from volunteer
      donors who were not drug users. The samples were analyzed in the laboratory using
      the two-panel Cozart RapiScan cartridge for opiates and cocaine and confirmed
      using gas chromatography-mass spectrometry (GC-MS). The samples were stored
      frozen at -20 degrees C until analysis by GC-MS. The overall accuracy of the CRS
      for both opiates and cocaine was 100%. Samples spiked at 50% above and below the
      cut-off consistently gave negative and positive results respectively. A total of
      88 samples were positive for various opiates and 111 samples were positive for
      cocaine and/or its metabolites. The CRS for opiates and cocaine in oral fluid,
      using a cut-off of 30 ng/mL morphine or benzoylecgonine equivalents in neat oral
      fluid, had overall efficiencies of 98% and 99%, respectively, versus GC-MS. A
      series of potential adulterants of oral fluid were evaluated and shown not to
      alter the outcome of the test result.

PMID- 15944066
TI  - The association between viral clearance and depression in patients with hepatitis
      C receiving interferon-alpha and ribavirin.

PMID- 15944067
TI  - Chronic stress and comfort foods: self-medication and abdominal obesity.
AB  - Central corticotropin-releasing factor (CRF) networks are recruited by chronic
      stressors and elevated glucocorticoids (GCs) that initiate recruitment of central
      CRF activity in the amygdala. Increased central activity of the CRF network
      stimulates all monoaminergic cell groups, as well as premotor autonomic and other
      limbic structures resulting in the typical arousal, behavioral changes,
      autonomic, and neuroendocrine changes that accompany the chronic imposition of a
      stressor. By contrast, elevated GCs appear, through a variety of means to
      counteract the effects of central CRF, which they have initiated. Together with
      insulin, the GCs stimulate drive for and ingestion of "comfort foods" that may
      directly result in reduction of the negative effects of the chronic stressor in
      the nucleus Accumbens, through stimulation of the anterior, more pleasure
      associated part of this cell group, thus reducing the weight of the stress
      stimulated posterior, more defensive part. Furthermore, the shift in caloric
      intake from chow to preference for "comfort foods," together with elevated GCs
      and insulin, reorganize energy stores from a peripheral to a central
      distribution, primarily as abdominal fat. A signal associated with this fat depot
      appears, as with eating "comfort foods," to reduce the influence of the chronic
      stress network on behaviors, autonomic, and neuroendocrine outflow.

PMID- 15944068
TI  - The potential influence of maternal stress hormones on development and mental
      health of the offspring.
AB  - Recent studies in humans suggest that alterations in the activity of the
      neuroendocrine system mediate the effects of psychosocial stress on fetal
      development and birth outcome. Chronic maternal distress compromises the normal
      regulation of hormonal activity during pregnancy and elevates free circulating
      corticotrophin-releasing hormone (CRH), probably of placental origin, before the
      normal increase occurs at term. Excess CRH, and other hormones like cortisol and
      met-enkephalin that pass through the placenta, could precipitate preterm labor,
      reduce birth weight and slow growth rate in prenatally stressed infants. CRH
      and/or cortisol have also been associated with impaired fetal habituation to
      stimuli and temperamental difficulties in infants. These changes may result from
      actions of the hormones on their receptors in the fetal limbic system. In the
      rat, gestational stress and excess maternal and fetal plasma corticosterone cause
      downregulation of fetal glucocorticoid (GR) and mineralocorticoid (MR) receptors
      and impair the feedback regulation of the hypothalamic-pituitary adrenal (HPA)
      axis in infancy and adulthood. The impairment in HPA axis activity can be
      prevented by maternal adrenalectomy and mimicked by administration of
      glucocorticoids. Gestational stress also increases CRH activity in the amygdala
      and the incidence of anxiogenic and depressive-like behavior in rats and non
      human primates, which can be ameliorated by CRH antagonists. Excess amounts of
      CRH and cortisol reaching the human fetal brain during periods of chronic
      maternal stress could alter personality and predispose to attention deficits and
      depressive illness through changes in neurotransmitter activity.

PMID- 15944069
TI  - Translational research using in vivo measures of primary antibody responses.

PMID- 15944070
TI  - Social stress and the regulation of tumor necrosis factor-alpha secretion.
AB  - Social disruption (SDR), a murine model of social stress, altered the phenotype
      and function of spleen immune cells. Previous reports indicated that following
      SDR spleens contained higher numbers of CD11b+ monocytes, and these cells were
      less sensitive to the inhibitory effects of glucocorticoids on cell viability.
      Additionally, lipopolysaccharide (LPS)-stimulated splenocytes from SDR mice
      secreted higher levels of the proinflammatory cytokines tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-6 compared to splenocytes from controls. The
      present study sought to further examine the effects of SDR on TNFalpha secretion
      from splenocytes. We report that SDR increased TNFalpha secretion from an
      enriched fraction of CD11b+ monocytes stimulated with LPS. Additionally, SDR
      altered the kinetics of TNFalpha release from LPS-stimulated splenocytes and
      induced minor changes in the suppressive effects of corticosterone and
      norepinephrine on LPS-induced TNFalpha secretion. These results are in agreement
      with the notion that complex interactions mediate the response to social stress.

PMID- 15944071
TI  - Repeated acupuncture treatment affects leukocyte circulation in healthy young
      male subjects: a randomized single-blind two-period crossover study.
AB  - Acupuncture is the most popular component of traditional Chinese medicine in
      western countries, which has been widely used in the treatment of numerous
      medical conditions, e.g., pain, emesis or asthma. However, the effects of
      acupuncture on neuroendocrine and immune functions in humans remain unclear.
      Therefore, the present study was performed to analyse whether acupuncture
      treatment affects leukocyte circulation as well as plasma levels of cortisol and
      norepinephrine in humans. Ten healthy young male subjects were enrolled in a
      randomized single-blind two-period crossover study. Each period contained three
      sessions of either acupuncture or sham acupuncture (placebo) treatment. After
      randomisation, the group 1 (n=5) received acupuncture treatment at acu-points
      ST36, LI11, SP10, and GV14, while sham acupuncture was performed for group 2
      (n=5). Two weeks later, each group received the alternative treatment. Blood
      samples were taken before needling, 10 min after, and 30 min after removing the
      needles in the first and the third session. In addition, blood pressure and heart
      rate were determined simultaneously. Although acupuncture treatment did not
      affect leukocyte circulation in peripheral blood after the first session, we
      observed a significant decrease in leukocyte and lymphocyte values after the
      third session. In contrast, cortisol and norepinephrine plasma levels remained
      unchanged by acupuncture. These data indicate that repeated acupuncture treatment
      can affect leukocyte circulation in healthy humans by still unknown mechanisms.

PMID- 15944072
TI  - The association between life events, social support, and antibody status
      following thymus-dependent and thymus-independent vaccinations in healthy young
      adults.
AB  - This study determined whether stressful life events and social support were
      related to antibody status following both thymus-dependent and thymus-independent
      vaccinations. Life events in the previous year and customary social support were
      measured in 57 healthy students at baseline. Antibody status was also assessed at
      baseline and at five weeks and five months following vaccination with the
      trivalent influenza vaccine and the meningococcal A+C polysaccharide vaccine.
      Taking into account baseline antibody titre, high life events scores prior to
      vaccination were associated with lower responses to the B/Shangdong influenza
      strain at both five weeks and five months and meningococcal C at five weeks. Life
      event scores were not associated with response to the other two influenza viral
      strains nor response to meningococcal A. Those with high social support scores
      had stronger 5-week and 5-month antibody responses to the A/Panama influenza
      strain, but not to any of the other strains. These associations could not be
      accounted for by demographic or health behaviour factors, and also emerged from
      analyses comparing those who exhibited a fourfold increase in antibody titre from
      baseline with those who did not. Life events and social support were related to
      antibody status following influenza vaccination in distinctive ways that may be
      partly determined by vaccine novelty and prior naturalistic exposure. Life events
      also predicted poor antibody response to meningococcal C polysaccharide
      vaccination after previous meningococcal C conjugate vaccination. Neither
      psychosocial factor was associated with response to primary meningococcal A
      polysaccharide vaccination.

PMID- 15944073
TI  - Activation in vagal afferents and central autonomic pathways: early responses to
      intestinal infection with Campylobacter jejuni.
AB  - Abundant evidence now supports the idea that multiple pathways or mechanisms
      underlie communication from the immune system to the brain. The presence of a
      variety of mechanisms suggests that they may each contribute something different
      to immunosensory signaling. For instance, brain mediated immune signal
      transduction is dependent upon the presence of circulating mediators whereas
      peripheral sensory nerves are more likely to be important early on in an
      infection, prior to elevation of circulating cytokines, or in local infections
      within the terminal fields of these nerves. To test the hypothesis that local
      infection in the gut activates vagal sensory neurons, we assessed expression of
      the neuronal activation marker c-Fos in neurons in the vagal sensory ganglia and
      in the primary sensory relay nucleus for the vagus, the nucleus of the solitary
      tract (nTS) in mice treated orally either with saline or live Campylobacter
      jejuni (C. jejuni). Male CF1 mice were inoculated orally with either C. jejuni or
      saline, and c-Fos expression in the vagal sensory neurons and brain 4-12 h later
      was assessed via immunohistochemistry. Oral inoculation with C. jejuni led to a
      significant increase in c-Fos expression in neurons bilaterally in the vagal
      ganglia, in the absence of elevated levels of circulating pro-inflammatory
      cytokines. C. jejuni treatment activated neurons in the nTS, as well as in brain
      regions associated with primary viscerosensory pathways and the central autonomic
      network. These findings provide evidence that peripheral sensory neurons
      contribute an early signal to the brain regarding potential pathogens.

PMID- 15944074
TI  - Acute inflammation and negative mood: mediation by cytokine activation.
AB  - Inflammatory diseases are commonly associated with depressed mood. This
      association may be influenced by the production of proinflammatory cytokines.
      Accordingly, we assessed whether cytokine levels and mood (measured with the
      profile of mood states) could be altered by a mild, non-sickness inducing, acute
      inflammatory stimulus. Using a randomised placebo-controlled, double-blind
      design, 30 healthy male volunteers were injected with Salmonella typhi vaccine or
      placebo. Assessments of mood, symptoms of illness and temperature were made at
      baseline and at 1.5, 3, and 6 h post-injection. Plasma concentrations of
      interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1Ra), and tumour
      necrosis factor-alpha (TNF-alpha) were assessed at baseline and 3 h post
      injection. No significant symptoms of illness were reported in either group. Mood
      was more negative following injection in the vaccine than the placebo group, and
      the vaccine group experienced a 106% increase in IL-6 concentration. Negative
      changes in mood following injection were significantly correlated with increases
      in IL-6 production. No changes in TNF-alpha or IL-1Ra concentration were recorded
      in either group. It is concluded that S. typhi vaccination may be a useful model
      of mild inflammatory challenge, producing a significant transient cytokine
      induced decrease in mood in the absence of any febrile response. Implications for
      depressed mood in physical illness are discussed.

PMID- 15944075
TI  - 3-aminobenzamide prevents restraint-evoked immunocompromise.
AB  - Chronic stressors compromise immune function, which may affect disease state in
      rats and mice. Although the molecular mechanism(s) underlying the link between
      psychological stressors and physiological responses remain elusive, one putative
      mechanism is oxidative stress. DNA damage activates poly(ADP-ribose) polymerase
      (PARP), a nuclear enzyme that participates in DNA repair; if DNA damage is
      extensive, however, then PARP becomes cytotoxic. Because PARP-1-/- transgenic
      mice are resistant to chronic stress-induced immunocompromise, we tested the
      hypothesis that pre-restraint administration of 3-aminobenzamide (3-AB), a PARP
      inhibitor, would prevent restraint-evoked suppression of antibody production to
      the novel protein, keyhole limpet hemocyanin (KLH). Mice were physically
      restrained for 3 h daily for 14 consecutive days, then immunized with KLH. Daily
      restraint continued for an additional 21 days and anti-KLH IgG production was
      assessed. Mice exposed to repeated restraint reduced concentrations of anti-KLH
      IgG, whereas, mice treated with 3-AB (0.5, 5.0, or 20.0 mg/kg) prior to each bout
      of restraint displayed anti-KLH IgG concentrations similar to those of
      unrestrained mice. Treatment with 3-AB (0.5 and 5.0 mg/kg) during the restraint
      paradigm also facilitated habituation of the corticosterone response to
      restraint, and 3-AB (0.5 mg/kg) reduced the effect of repeated restraint on body
      mass. However, the immunoprotective effects of 3-AB and the endocrine and
      metabolic effects appear to be distinctly regulated because, unlike the endocrine
      and metabolic effects, the immunoprotective effects of 3-AB were independent of
      dose. These data suggest that PARP inhibitors may be useful to prevent
      compromised immune function in response to stressors.

PMID- 15944076
TI  - The exercise-induced enhancement of influenza immunity is mediated in part by
      improvements in psychosocial factors in older adults.
AB  - The primary goal of this study was to determine whether exercise-associated
      improvements of the immune response to influenza vaccination were mediated by
      improvements in psychosocial factors in older adults. At baseline, prior to the
      exercise intervention, older adult participants were immunized with influenza
      vaccine. Blood samples collected pre-immunization, 1, 4, and 12 weeks post
      immunization were analyzed for anti-influenza antibody, whereas influenza
      specific cytokine (IFNgamma) was evaluated at 1 week post-immunization.
      Depression and sense of coherence were measured pre-immunization. Four weeks post
      immunization, participants were randomly assigned to either an aerobic exercise
      group (n=14) or a control group (n=14). After a 10-month exercise intervention,
      the immunization, blood collections, and psychosocial measures were repeated. At
      the post-intervention evaluation, exercise participants had improved scores on
      depression and sense of coherence. Also post-intervention, exercise participants
      had a greater increase in antibody and IFNgamma production. After controlling for
      the effect of both psychosocial measures, the exercise treatment remained
      significant with respect to antibody titer suggesting that the increases in
      antibody were not mediated by improvement in the psychosocial factors. In
      contrast, the enhancement of IFNgamma appeared to be mediated at least in part by
      the psychosocial factors. After controlling for psychosocial factors, exercise
      treatment was no longer significantly related to the change in IFNgamma. Taken
      together, our findings may suggest that the mechanism(s) of exercise-induced
      improvement in immunocompetence involve both physiological and psychological
      pathways.

PMID- 15944078
TI  - The hemolymph proteome of Anopheles gambiae.
AB  - We used two-dimensional SDS-PAGE and microsequencing or peptide mass
      fingerprinting to identify major proteins in the hemolymph of Anopheles gambiae.
      We found approximately 280 protein spots in hemolymph and identified 28 spots,
      representing 26 individual proteins. Most of these proteins have known or
      predicted functions in immunity, iron transport, or lipid biology. Many of the
      proteins have been found in hemolymph in other insects but one protein is novel:
      a new member of the ML family (involved in lipid recognition). Three of the
      identified proteins increased in spot intensity or appeared de novo following
      bacterial injection: a phenoloxidase, and two chitinase-like proteins. A subset
      of proteins decreased following bacterial injections: these included the light
      and heavy chains of ferritin. Several proteins appeared in hemolymph following
      any wound or injection. Most of these are metabolic enzymes lacking signal
      peptides that are likely to be released as a result of damage to muscles and
      other tissues by injury. The map will provide a useful tool for examining changes
      in hemolymph proteins following blood feeding and infection by parasites.

PMID- 15944077
TI  - Comparative analysis of BAC and whole genome shotgun sequences from an Anopheles
      gambiae region related to Plasmodium encapsulation.
AB  - The only natural mechanism of malaria transmission in sub-Saharan Africa is the
      mosquito, generally Anopheles gambiae. Blocking malaria parasite transmission by
      stopping the development of Plasmodium in the insect vector would provide a
      useful alternative to the current methods of malaria control. Toward this end, it
      is important to understand the molecular basis of the malaria parasite refractory
      phenotype in An. gambiae mosquito strains. We have selected and sequenced six
      bacterial artificial chromosome (BAC) clones from the Pen-1 region that is the
      major quantitative trait locus involved in Plasmodium encapsulation. The sequence
      and the annotation of five overlapping BAC clones plus one adjacent, but not
      contiguous clone, totaling 585kb of genomic sequence from the centromeric end of
      the Pen-1 region of the PEST strain were compared to that of the genome sequence
      of the same strain produced by the whole genome shotgun technique. This project
      identified 23 putative mosquito genes plus putative copies of the
      retrotransposable elements BEL12 and TRANSIBN1_AG in the six BAC clones. Nineteen
      of the predicted genes are most similar to their Drosophila melanogaster homologs
      while one is more closely related to vertebrate genes. Comparison of these new
      BAC sequences plus previously published BAC sequences to the cognate region of
      the assembled genome sequence identified three retrotransposons present in one
      sequence version but not the other. One of these elements, Indy, has not been
      previously described. These observations provide evidence for the recent active
      transposition of these elements and demonstrate the plasticity of the Anopheles
      genome. The BAC sequences strongly support the public whole genome shotgun
      assembly and automatic annotation while also demonstrating the benefit of
      complementary genome sequences and of human curation. Importantly, the data
      demonstrate the differences in the genome sequence of an individual mosquito
      compared to that of a hypothetical, average genome sequence generated by whole
      genome shotgun assembly.

PMID- 15944079
TI  - Characterization of the SCP/TAPS gene family in Drosophila melanogaster.
AB  - The SCP/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) gene family encodes proteins found in many
      eukaryotes. SCP/TAPS proteins are defined by the presence of an SCP/TAPS domain,
      and many participate in important physiological processes. Five SCP/TAPS genes
      were previously identified in Drosophila melanogaster and are expressed in the
      digestive tract or in the testes. Sequence databases were searched to determine
      if other SCP/TAPS genes were present in D. melanogaster, and an additional 21
      SCP/TAPS genes were identified. To further define the roles of these genes, the
      structures of each gene and protein were analyzed. Based on these analyses, 25
      SCP/TAPS genes could be placed into one of two groups. Each group contained
      conserved intron positions that were not shared with the other group. Proteins
      encoded by group 1 genes also shared additional sequence motifs and conserved
      cysteines not found in group 2 proteins. To determine if the two groups were
      expressed differently, reverse transcriptase (RT)-polymerase chain reaction (PCR)
      was used to examine expression in adult flies. The results indicated that most
      genes were preferentially expressed in adult males, suggesting a role for these
      genes in male reproduction. Members of both groups displayed this preferential
      expression, so it was not group-specific. The two groups may differ in
      localization rather than function.

PMID- 15944080
TI  - Identification of cytochrome P450 and glutathione-S-transferase genes
      preferentially expressed in chemosensory organs of the swallowtail butterfly,
      Papilio xuthus L.
AB  - The swallowtail butterfly, Papilio xuthus L., feeds exclusively on members of the
      plant family, Rutaceae. Female butterflies lay eggs in response to specific
      chemicals contained in their host plants. They perceive a variety of polar
      compounds as oviposition stimulants through the tarsal chemosensilla of the
      foreleg by drumming upon the leaf surface. We undertook an expressed sequence tag
      (EST) analysis to identify the chemosensory-related genes that are expressed in
      chemosensilla on the tarsus of P. xuthus. Several genes that showed similarity
      with biotransformation enzymes were identified from the ESTs. Among them, a
      cytochrome P450 and a glutathione-S-transferase (GST) were preferentially
      expressed in the chemosensory organs. We have determined the structure of both
      cDNA and genomic sequences encoding these enzymes and designated the P450 as
      CYP341A2, a novel member of CYP341A subfamily, and the GST as GST-pxcs1,
      respectively. We observed a localized expression of CYP341A2 at the base of
      tarsal chemosensilla by in situ hybridization. These results suggest that these
      degrading enzymes play a role in the chemosensory reception for host plant
      recognition.

PMID- 15944081
TI  - Characterization of cDNAs encoding three trypsin-like proteinases and mRNA
      quantitative analysis in Bt-resistant and -susceptible strains of Ostrinia
      nubilalis.
AB  - Our previous studies suggested that Bacillus thuringiensis (Bt) resistance in a
      Dipel-resistant strain of Ostrinia nubilalis was primarily due to reduced trypsin
      like proteinase activity. In this study, we demonstrated a 254-fold resistance to
      Cry1Ab protoxin but only 12-fold to trypsin-activated Cry1Ab toxin in the Dipel
      resistant strain. Significantly higher resistance to Cry1Ab protoxin than to
      trypsin-activated Cry1Ab toxin further supports the hypothesis that reduced
      trypsin-like proteinase activity leading to reduced activation of the Bt protoxin
      is a major resistance mechanism in the Dipel-resistant strain. To understand the
      molecular basis of reduced proteinase activity, three cDNAs, OnT2, OnT23, and
      OnT25, encoding full-length trypsin-like proteinases, were sequenced in Bt
      resistant and -susceptible O. nubilalis larvae. Although a number of nucleotide
      differences were found in sequences from the Bt-resistant and -susceptible
      strains, the differences were not consistent with reduced trypsin-like activity
      in the Bt-resistant strain. However, the mRNA levels of OnT23 in the resistant
      strain were 2.7- and 3.8-fold lower than those of the susceptible strain as
      determined by northern blotting and real-time quantitative PCR, respectively.
      Thus, reduced trypsin-like activity may be attributed to reduced expression of
      OnT23 in Bt-resistant O. nubilalis. Our study provides new insights into Bt
      resistance management strategies, as resistance mediated by reduced Bt protoxin
      activation would be ineffective if resistant insects ingest a fully activated
      form of Cry1Ab toxin, either in spray formulations or transgenic Bt crops.

PMID- 15944082
TI  - Elevated activity of an Epsilon class glutathione transferase confers DDT
      resistance in the dengue vector, Aedes aegypti.
AB  - Glutathione transferases (GSTs) play a central role in the detoxification of
      xenobiotics such as insecticides and elevated GST expression is an important
      mechanism of insecticide resistance. In the mosquito, Anopheles gambiae,
      increased expression of an Epsilon class GST, GSTE2, confers resistance to DDT.
      We have identified eight GST genes in the dengue vector, Aedes aegypti. Four of
      these belong to the insect specific GST classes Delta and Epsilon and three are
      from the more ubiquitously distributed Theta and Sigma classes. The expression
      levels of the two Epsilon genes, a Theta GST and a previously identified Ae.
      aegypti GST [Grant and Hammock, 1992. Molecular and General Genetics 234, 169
      176] were established for an insecticide susceptible and a resistant strain. We
      show that the putative ortholog of GSTe2 in Ae. aegypti (AaGSTe2) is over
      expressed in mosquitoes that are resistant to the insecticides DDT and
      permethrin. Characterisation of recombinant AaGSTE2-2 confirmed the role of this
      enzyme in DDT metabolism. In addition, unlike its Anopheles ortholog, AaGSTE2-2
      also exhibited glutathione peroxidase activity.

PMID- 15944083
TI  - Characterization of a D2-like dopamine receptor (AmDOP3) in honey bee, Apis
      mellifera.
AB  - Dopamine is an important neurotransmitter in vertebrate and invertebrate nervous
      systems and is widely distributed in the brain of the honey bee, Apis mellifera.
      We report here the functional characterization and cellular localization of the
      putative dopamine receptor gene, Amdop3, a cDNA clone isolated and identified in
      previous studies as AmBAR3 (Apis mellifera Biogenic Amine Receptor 3). The Amdop3
      cDNA encodes a 694 amino acid protein, AmDOP3. Comparison of AmDOP3 to Drosophila
      melanogaster sequences indicates that it is orthologous to the D2-like dopamine
      receptor, DD2R. Using AmDOP3 receptors expressed in HEK293 cells we show that of
      the endogenous biogenic amines, dopamine is the most potent AmDOP3 agonist, and
      that activation of AmDOP3 receptors results in down regulation of intracellular
      levels of cAMP, a property characteristic of D2-like dopamine receptors. In situ
      hybridization reveals that Amdop3 is widely expressed in the brain but shows a
      pattern of expression that differs from that of either Amdop1 or Amdop2, both of
      which encode D1-like dopamine receptors. Nonetheless, overlaps in the
      distribution of cells expressing Amdop1, Amdop2 and Amdop3 mRNAs suggest the
      likelihood of D1:D2 receptor interactions in some cells, including subpopulations
      of mushroom body neurons.

PMID- 15944084
TI  - The cathepsin L-like proteinases from the midgut of Tenebrio molitor larvae:
      sequence, properties, immunocytochemical localization and function.
AB  - CDNAs coding for five procathepsin L-like proteinases (pCALs) were cloned and
      sequenced from a cDNA library prepared from Tenebrio molitor larval midguts:
      pCAL1a (with the isoforms pCAL1b and pCAL1c), pCAL2, and pCAL3. All the pCALs
      have the active residues Cys 25, His 169, Asn 175, and Gln 19 (papain numbering),
      the ERFNIN motif of papain-like enzymes and their sequences are homologous to
      cathepsin L enzymes. pCAL1a was expressed in bacterial systems. It is auto
      catalytically activated at low pH, has kinetic properties and N-terminal sequence
      identical to hemocyte cathepsin L-like proteinase (CAL) and was used to raise
      antibodies. Semi-quantitative RT-PCR data showed that mRNAs for pCAL2 and pCAL3
      were transcribed in midgut and in lesser amounts in hemolymph, whereas that for
      pCAL1a was transcribed in these tissues and also in fat body, Malpighian tubules,
      and carcass. Imunochemical detection recognized pCAL1a translation in all tissue
      homogenates, except anterior midgut. At this region, the presence of pCAL2 is
      suggested on the grounds of electrophoretical migration and high recovery of CAL2
      activity from anterior midgut cells and from isolated midgut contents.
      Immunocytochemical localization data revealed that pCAL1a occurs in lysosome-like
      vesicles in all tissues, except anterior midgut, where a labelling considered to
      correspond to pCAL2 is found in large acidic granules being released by apocrine
      secretion. Putative pCAL2 was also detected in midgut contents, probably in the
      form of CAL2, the major luminal CAL, which was purified to homogeneity. A
      cladogram of insect CALs result in a monophyletic branch with lysosomal T.
      molitor enzymes and enzymes from five insect orders and in a polyphyletic array
      of coleopteran sequences, including digestive CALs from T. molitor. The data
      suggest that only Coleoptera have digestive CALs that may originate by gene
      duplication and independent evolution relative to the gene encoding the lysosomal
      enzyme.

PMID- 15944086
TI  - Mutations in the desat1 gene reduces the production of courtship stimulatory
      pheromones through a marked effect on fatty acids in Drosophila melanogaster.
AB  - In Drosophila melanogaster, desat1 is involved in the synthesis of fatty acids
      (FAs), some of which are precursors in the production of unsaturated hydrocarbons
      (HCs) in position 7 (7-HC) that play an important role in mating behaviour. Three
      GS lines with P-element insertion in the desat1 promoter showed more or less
      decrease in 7-HC, depending on the site of insertion. The forced transcription of
      genomic 5'P-flanking sequence led to opposite effects upon 7-HC, depending on the
      orientation of the insertions. Homozygous GS12251 flies showed particularly low 7
      HC levels and severely affected courtship parameters (courtship latency doubled,
      number of copulation attempts decreased by half). After transposon excision, the
      HC phenotype was reversed in most lines, showing that the location of the
      transposon was responsible for the mutant phenotype. In homozygous GS12251 flies,
      the amounts of FAs and desat1 transcripts were reduced by half, compared to the
      amounts in heterozygous or wild-type flies. Relative proportions among FAs were
      quite similar to those of wild-type, with the exception of a slight decrease in
      myristoleic, palmitoleic and vaccenic acid. As the reduction of desat1 activity
      in the mutant resulted in a large decrease in both unsaturated and saturated FAs,
      it could impair FA and lipid metabolism, as it is known in vertebrates.

PMID- 15944085
TI  - Generation of a novel Wolbachia infection in Aedes albopictus (Asian tiger
      mosquito) via embryonic microinjection.
AB  - Genetic strategies that reduce or block pathogen transmission by mosquitoes are
      being investigated as a means to augment current control measures. Strategies of
      vector suppression and replacement are based upon intracellular Wolbachia
      bacteria, which occur naturally in many insect populations. Maternally inherited
      Wolbachia have evolved diverse mechanisms to manipulate host insect reproduction
      and promote infection invasion. One mechanism is cytoplasmic incompatibility (CI)
      through which Wolbachia promotes infection spread by effectively sterilizing
      uninfected females. In a prior field test, releases of Wolbachia-infected males
      were used to suppress a field population of Culex pipiens. An additional strategy
      would employ Wolbachia as a vehicle to drive desired transgenes into vector
      populations (population replacement). Wolbachia-based population suppression and
      population replacement strategies require an ability to generate artificial
      Wolbachia associations in mosquitoes. Here, we demonstrate a technique for
      transferring Wolbachia (transfection) in a medically important mosquito species:
      Aedes albopictus (Asian tiger mosquito). Microinjection was used to transfer
      embryo cytoplasm from a double-infected Ae. albopictus line into an aposymbiotic
      line. The resulting mosquito line is single-infected with the wAlbB Wolbachia
      type. The artificially generated infection type is not known to occur naturally
      and displays a new CI crossing type and the first known example of bidirectional
      CI in Aedes mosquitoes. We discuss the results in relation to applied mosquito
      control strategies and the evolution of Wolbachia infections in Ae. albopictus.

PMID- 15944087
TI  - Survey of long terminal repeat retrotransposons of domesticated silkworm (Bombyx
      mori).
AB  - Long terminal retrotransposons are major components of eukaryotic transposable
      elements. We have surveyed the long terminal repeats (LTR) retrotransposons of
      domesticated silkworm (Bombyx mori) by mining the data produced by Bombyx mori
      Genome Sequencing Project. At least 29 separate families of LTR retrotransposons
      are identified in this survey, comprising of 11.8% of the complete sequence.
      Families of domesticated silkworm LTR retrotransposons can be mainly classified
      into three groups: gypsy-like, copia-like, Pao-Bel. Fourteen families identified
      consist of gypsy-like elements, four families consist of copia-like elements and
      seven families consist of Pao-Bel elements. In addition to the three groups of
      LTR retrotransposons, two families of unusual non-coding elements are identified
      in the genome of this species. Further phylogenetic analysis of RT domain
      indicates that the elements of B.mori show high diversity and can form different
      clades in each group. An analysis of sequence variation from different families
      reveals distinct patterns of variation for the elements belonging to three
      groups. The analysis of the domesticated silkworm LTR retrotransposons should
      assist in our understanding of the roles of retroelement in lepidopteron insect
      genome evolution.

PMID- 15944089
TI  - Have all the ICD primary prevention trials excluded an important group of
      patients?
AB  - Primary prevention trials of implantable cardioverter defibrillator (ICD) therapy
      have generally excluded patients early after revascularization. Clinicians are
      commonly faced with patients who have ventricular dysfunction and nonsustained
      ventricular tachyarrhythmia developing shortly after revascularization. Since
      there are no evidence-based guidelines, management is currently at the discretion
      of the treating clinician. Recently, evidence has emerged that this patient
      population is at increased risk of development of life-threatening ventricular
      tachyarrhythmia and, pending prospective trials, we suggest that ICD therapy
      should be used in appropriately selected patients with perioperative ventricular
      arrhythmia.

PMID- 15944088
TI  - Molecular identification of a bevy of serine proteinases in Manduca sexta
      hemolymph.
AB  - Extracellular serine proteinase pathways control immune and homeostatic processes
      in insects. Our current knowledge of their components is limited-prophenoloxidase
      activating proteinases (PAPs) are among the few hemolymph proteinases (HPs) with
      known functions. To identify components of proteinase systems in the hemolymph of
      Manduca sexta, we amplified cDNAs from larval fat body or hemocytes using
      degenerate primers coding for two conserved regions in S1 family serine
      proteinases. PCR yielded fragments encoding seven known (HP1-HP4, PAP-1, PAP-2
      and PAP-3) and 18 unknown (HP5-HP22) serine proteinases. We screened cDNA
      libraries and isolated clones for 17 of the newly discovered HPs (HP5-HP22 except
      for HP11) and prepared antibodies to 14 recombinant proteins (HP6, HP8-HP10,
      HP12, HP14-HP19, HP21 and HP22). Fourteen of the HPs contain regulatory clip
      domain(s) at their amino-terminus--HP1, HP2, HP6, HP8, HP13, HP17, HP18, HP21,
      HP22 and PAP-1 have one, whereas HP12, HP15, PAP-2 and PAP-3 have two clip
      domains. Multiple sequence alignment of catalytic domains in these and other
      arthropod serine proteinases provided useful clues for future functional
      analysis. Northern blot and reverse transcription PCR (RT-PCR) analyses showed
      increases in HP2, HP7, HP9, HP10, HP12-HP22 mRNA levels at 24h after a bacterial
      challenge, and immunoblot analysis confirmed elevated concentrations of HP12,
      HP14-HP19, HP21 and HP22 proteins in plasma in response to injected bacteria.
      Hemocytes express HP13 and HP18; fat body produces HP12, HP20-HP22; both tissues
      synthesize the other HPs. These results collectively indicate the existence of a
      complex serine proteinase network in M. sexta hemolymph, predicted to mediate
      rapid defense responses upon wounding and/or microbial infection.

PMID- 15944090
TI  - What is the "optimal" follow-up schedule for ICD patients?
AB  - BACKGROUND: In the absence of comparative studies, recommended routine follow-up
      (FU) intervals for implantable cardioverter defibrillator (ICD) patients range
      from 1 to 6 months; most patients are followed at 3 month intervals. METHODS: Six
      hundred and eighteen ICD patients were routinely seen 4 weeks after implant and
      then every 3 months. Unplanned visits (UPV) were either patient initiated or due
      to manufacturer recalls. FU visits included patient history/examination, ICD
      interrogation, pacing/sensing threshold and pacing/shock impedance. Chest X-rays
      were performed every 6 months. To validate FU interval recommendations, a
      comparative analysis on the detection of complications was performed, relying
      either on the information of every, or of every other FU visit, i.e., on 3 or 6
      month intervals. RESULTS: During 3.3+/-2.8 years, 137 complications occurred in
      110 patients (17%). However, identification of only 34% was dependent on the FU
      schedule, since the mode of detection was ICD interrogation in 38 and
      history/physical examination in nine patients. The remainder was diagnosed by UPV
      in 47, manufacturer recall in seven, accidental discovery during device
      replacement in two, and routine X-ray in 34 patients. Complication free survival
      at 2 years was 86.4% for patients implanted before 1999, and 89.2% thereafter
      (P=0.003). Regarding 6 rather than 3 month FU intervals, a theoretical maximum
      delay of 3 months in the detection of potentially life-threatening complications
      would have occurred in 1.7% of all patients. For those implanted after 1999, this
      related to only 0.9%. CONCLUSIONS: ICD-related complications detected during
      routine FU visits are relatively rare, particularly with newer generation ICD
      systems. Thus, 6 month FU intervals appear to be safe. With new developments such
      as patient alert features and telemedical data transmission, FU intervals in ICD
      clinics might even be further extended.

PMID- 15944091
TI  - n-3 Fatty acids and ventricular arrhythmias in patients with ischaemic heart
      disease and implantable cardioverter defibrillators.
AB  - AIM: To investigate the relationship between serum content of n-3 polyunsaturated
      fatty acids (PUFA) and the incidence of ventricular arrhythmias in patients with
      an implantable cardioverter defibrillator (ICD). METHODS: We included 98 patients
      with ischaemic heart disease and an ICD. The numbers of ventricular fibrillation
      (VF) and ventricular tachycardia (VT) events were assessed during a 12-month
      period and related to the concentration of n-3 PUFA in serum phospholipids.
      RESULTS: Patients with more than one arrhythmic event had significantly lower n-3
      PUFA levels compared with patients without arrhythmias (mean 7.1% vs 9.2%,
      P<0.01). Dividing the patients into quintiles according to their n-3 PUFA level
      those with the lowest content of n-3 PUFA had more ventricular arrhythmias than
      patients with the highest concentration of n-3 PUFA (mean 1.3 event vs 0.2 event,
      P<0.05). CONCLUSION: Patients with a low content of n-3 PUFA in serum had a
      higher incidence of ventricular arrhythmias compared with patients with high
      serum levels of n-3 PUFA. The data suggest that the protection offered by n-3
      PUFA against sudden cardiac death observed in previous studies is mediated by a
      direct antiarrhythmic effect of n-3 PUFA.

PMID- 15944092
TI  - Arrhythmogenic right ventricular dysplasia presenting as right ventricular
      outflow tract tachycardia.
AB  - A case of a 51-year old male is presented. A left bundle branch block inferior
      axis tachycardia was manifest. At electrophysiological study this tachycardia was
      inducible and was ablated in the septal right ventricular outflow tract (RVOT).
      Two other tachycardias were identified both with right bundle branch block (RBBB)
      morphology raising the suspicion of diffuse pathology. Arrythmogenic right
      ventricular dysplasia (ARVD) was confirmed by right ventricular angiography and
      magnetic resonance imaging (MRI). An implantable cardioverter defibrillator (ICD)
      was implanted and an appropriate shock was later delivered.

PMID- 15944093
TI  - Focal right ventricular tachycardia originating from the subtricuspid septum.
AB  - Ventricular tachycardia originating from the right ventricular septum is very
      uncommon. In a 54-year-old male patient with right ventricular tachycardia, the
      focus of the ventricular tachycardia was localized to the subtricuspid septum of
      the right ventricle, which could be successfully eliminated with radiofrequency
      catheter ablation. The patient's echocardiogram and coronary angiogram were
      normal. The available literature on idiopathic right ventricular tachycardia is
      reviewed.

PMID- 15944094
TI  - Do we need pacemakers resistant to magnetic resonance imaging?
AB  - AIMS: Manufacturers of pacemakers (PM) and of magnetic resonance imaging (MRI)
      devices state that MRI scanning of PM wearers is contraindicated. This paper
      tries to summarise which effects can interfere with PM, what can be hazardous,
      and how treatment of PM in MRI can be modified to guarantee compatibility.
      MATERIAL AND METHODS: All PM tested were from deceased patients. Reed contact
      thresholds and reactions were investigated in low magnetostatic fields and
      compared with those in strong magnetostatic fields. Influence of gradient fields
      on PM and heating due to radiofrequency (RF) pulses were estimated. Thirty Legal
      Medicine Departments were questioned whether deaths of PM patients during MRI are
      known. RESULTS: Reed contacts are influenced above 0.7 mT. In MRI fields only 28%
      of the PM in magnet mode remained so in all orientations. Of synchronous PM, 76%
      remained synchronous in all orientations. Gradient fields can influence sensing
      but cannot stimulate. Power density and temperature rise produced by RF fall
      rapidly with distance. Our question revealed six deaths. All suffered from sick
      sinus-syndrome and all were not PM dependent. In three cases ventricular
      fibrillation was proven as the cause of death. DISCUSSION: Asynchronous pacing
      due to magnetostatic and gradient fields may be problematic in patients with
      spontaneous rhythm. To avoid them, PM triggered MRI scan restricted to refractory
      period is proposed. Neither inhibition of PM nor heating of the electrode poses
      real risks. So far, we have examined eight patients 12 times in MRI triggered
      mode without problems.

PMID- 15944095
TI  - Effect of pacemaker rate-adaptation on 24 h beat-to-beat heart rate and blood
      pressure profiles.
AB  - AIMS: The aims of the study were to evaluate the 24-h beat-to-beat heart rate
      (RR) and blood pressure changes during closed loop stimulation (DDD-CLS) pacing
      and conventional fixed rate DDD pacing with respect to spontaneous activity.
      METHODS: We simultaneously and continuously measured beat-to-beat heart rate and
      blood pressure for 24 h in patients implanted with Inos2+ (Biotronik GmbH,
      Berlin, Germany). A randomised cross-over comparison of DDD-CLS and DDD pacing
      was performed by short- and long-term analyses. RESULTS: Seventeen patients (10
      males, aged 46-85 years) were enroled in the study: 11 completed the protocol.
      The percentage of atrial stimulation was 72.87% during DDD-CLS and 38.36% in DDD
      (P=0.003). All patients were 100% stimulated in the ventricle. On average, the
      percentage increase of paced RR intervals with respect to spontaneous beats was
      only 7.4% in DDD-CLS but 20.1% in DDD (P=0.0001). A significant correlation
      between spontaneous and paced RR profiles was obtained only during DDD-CLS (r(DDD
      CLS)=0.77, r(DDD)=0.23, P=0.01). Short-term analysis revealed a 3.79% reduction
      of the escape interval in DDD-CLS and 8.19% in DDD, and the relative fall in
      diastolic blood pressure was 1.14% in DDD-CLS and 3.81% in DDD. CONCLUSION: DDD
      CLS provided physiological heart rate fluctuations throughout the 24-h test. The
      blood pressure profiles of paced and spontaneous beats were comparable. The onset
      of paced rhythm in DDD-CLS resulted in a less pronounced decrease in heart rate
      and fall in diastolic pressure than in DDD.

PMID- 15944096
TI  - Prevention of pocket related complications with fibrin sealant in patients
      undergoing pacemaker implantation who are receiving anticoagulant treatment.
AB  - AIM: The aim of our study was to establish the efficiency of fibrin sealant in
      the prevention of pocket related complications in patients undergoing pacemaker
      implantation who are receiving anticoagulant treatment. METHODS: The study was
      performed on 40 and 41 patients prospectively randomized into treatment and
      control groups who underwent pacemaker implantation procedure between January
      2002 and July 2004 at the Pacemaker Center - Clinical Centre Nis, Serbia. Both
      groups of patients were receiving anticoagulant treatment with either heparin or
      warfarin. Surgical procedures between the groups differed only in the application
      of fibrin sealant prior to wound closure in the treatment group. RESULTS: In the
      treatment group, there were no pocket related complications while in the control
      group six patients (14.63%) had minor haematomas that required no treatment. Four
      patients (9.76%) had significant haematomas (two patients were treated
      conservatively while the other two needed reintervention). The INR in the
      treatment group was 2.76+/-0.85 and in the control group 2.65+/-0.79 (P=ns). In
      the follow-up period (2-27 months) no late complications were registered in
      either group. CONCLUSION: Fibrin sealant is an effective haemostatic agent. The
      results obtained in our study show that the administration of fibrin sealant in
      patients receiving anticoagulant treatment eliminates postoperative haematomas
      after pacemaker implantation.

PMID- 15944097
TI  - Cardiac resynchronisation therapy versus dual site right ventricular pacing in a
      patient with permanent pacemaker and congestive heart failure.
AB  - A 46-year-old male patient who had long-term right ventricular (RV) pacing for
      symptomatic complete heart block, initially by an epicardial, later with an
      endocardial pacing lead at the RV apex, developed congestive heart failure (CHF)
      and chronic atrial fibrillation 7 years following the pacemaker implantation and
      was medically treated. During follow-up, his pacemaker was upgraded to a cardiac
      resynchronisation therapy (CRT) device, because of uncontrolled CHF symptoms, New
      York Heart Association (NYHA) functional class IV, while on drugs. The patient's
      symptomatic status improved to NYHA functional class II with CRT. After 17 months
      of CRT, the battery became depleted, because of the high capture threshold of the
      left ventricular lead. The patient was then given dual site RV pacing (RV outflow
      tract+RV apex) in place of CRT, which showed similar efficacy at 12 weeks follow
      up.

PMID- 15944098
TI  - Optimized perioperative biventricular pacing in setting of right heart failure.
AB  - AIMS: A 78-year-old female with prior atrioventricular junctional ablation for
      paroxysmal atrial fibrillation and implantation of DDDR pacemaker underwent
      repair of severe tricuspid insufficiency. Effects of biventricular pacing were
      tested with temporary wires at the conclusion of cardiopulmonary bypass. METHODS:
      An ultrasonic flow probe was placed on the ascending aorta for real time cardiac
      output measurements. Atrioventricular delay optimization was performed and
      biventricular pacing was initiated while right-left ventricular delays were
      varied. RESULTS: There was no advantage of biventricular pacing (optimum right
      left ventricular delay of +80 ms) compared with existing DDD. CONCLUSIONS: This
      study confirms the physiological effects of right-left ventricular delay on
      cardiac output after cardiopulmonary bypass.

PMID- 15944099
TI  - Successful treatment of end-stage hypertrophic cardiomyopathy with biventricular
      cardiac pacing.
AB  - The beneficial use of biventricular pacing is reported in a patient with end
      stage hypertrophic cardiomyopathy, intraventricular conduction delay and
      echocardiographic evidence of intraventricular dyssyncrony. Marked improvement in
      clinical status, left ventricular ejection fraction and peak VO2 were observed.
      As far as we know, this is the first report of a beneficial effect of a
      biventricular device in this subset of patients, and may be worth further
      investigation.

PMID- 15944100
TI  - Explaining syncope: faints need not confuse.

PMID- 15944101
TI  - Angiotensin converting enzyme insertion/deletion polymorphisms in vasovagal
      syncope.
AB  - Recent studies suggest vasovagal syncope (VVS) has a significant heritable
      component (crude estimate sibling relative risk (lambda(s)): 1080) indicating
      that at least some forms of VVS may have a genetic cause. Here we present the
      first study examining a potential genetic abnormality in VVS. METHODS: DNA was
      collected from consecutive patients attending our unit with head up tilt
      confirmed VVS (n=165). One hundred and fourteen affected and unaffected first
      degree relatives of those with a definitive diagnosis of VVS and positive family
      history also provided DNA. RESULTS: DNA from 165 VVS index cases was genotyped
      for the ACE insertion/deletion polymorphism. Mean+/-SD age of cases was 56+/-19
      years (103 (62%) females). There was no significant difference in distribution of
      ACE insertion or deletion gene frequencies in cases compared with a large (>6000
      subjects) national control population. No preferential transmission of alleles in
      families was identified using tests of association (P=0.1789) CONCLUSION: We have
      shown using both a case control and a small family based association study that
      polymorphisms of ACE alone are not associated with increased risk of VVS. Further
      studies are planned to clarify the genotype/phenotype relationship in VVS and
      examine other candidate genes.

PMID- 15944102
TI  - Prospective evaluation of an educational programme for physicians involved in the
      management of syncope.
AB  - AIM: Management of patients (pts) presenting syncope diverges markedly from the
      guidelines of the European Society of Cardiology (ESC). To improve this
      management, the easiest option seemed to be to educate physicians. The aim of the
      study was to evaluate the impact of an educational process on the use of
      unnecessary neurological investigations. METHODS AND RESULTS: Charts of pts
      presenting syncope during two 12-month periods (1999-2000 and 2002-2003) to the
      emergency department were systematically reviewed. Between the two periods, all
      physicians in charge of pts with syncope attended educational meetings. During
      these meetings recommendations of the ESC were presented with a special emphasis
      on the uselessness of neurological investigations. Four hundred and fifty-four
      pts (1.2%) presented to the emergency department for syncope during study period
      1, and 524 (1.3%) during study period 2. Nineteen of the 169 pts (11%) directly
      discharged from the emergency department, had neurological investigations during
      study period 1 and 22 of the 279 (8%) during study period 2 (NS). In pts who were
      hospitalized, 48% had neurological investigations in groups 1 and 2. CONCLUSION:
      Education of physicians in charge of patients with syncope is inadequate to
      improve the cost effectiveness of the management of these patients.

PMID- 15944104
TI  - The evil complementary and alternative medicine!...the debate continues!

PMID- 15944105
TI  - Use of complementary and alternative medicine among cancer patients in Israel.
AB  - Complementary and alternative medicine (CAM) has gained in popularity among
      cancer patients in recent years. The present study assessed the patterns of CAM
      use among cancer patients in Israel. The design of the study was descriptive
      cross-sectional, and data were collected using a 27-item questionnaire. The
      sample consisted of 111 Israeli cancer patients who were part of a larger
      European study. Among the participants, past or current CAM use was reported by
      32.4% (n=36). The most common therapies used included herbal medicine (22.2%),
      spiritual therapies (19.4%), visualization and relaxation techniques (16.7% for
      each), and vitamins/minerals (13.9%). Younger patients with higher education,
      higher annual income, and previous standard treatment were more likely to use
      CAM. The mean satisfaction and perceived effectiveness scores were 5.36+/-1.37
      and 5.48+/-1.39, respectively, out of a maximum score of 7. The main benefits
      from CAM reported by patients included improvement in emotional and physical well
      being (40% and 34.3%, respectively) and increased ability to fight the disease
      (31.4%), although 17.1% of patients reported no benefits at all from CAM. The
      main sources of information about CAM were friends/family and the media. Findings
      suggest that due to the relatively high use of CAM among cancer patients, this
      topic should be taken into account in a holistic approach to this patient
      population.

PMID- 15944106
TI  - Use of complementary and alternative medicine in patients with cancer: a UK
      survey.
AB  - Over the past decade Complementary and Alternative Medicine (CAM) use in the UK
      has increased dramatically. However, little research appears to exist regarding
      its use in patients diagnosed with cancer. The study was descriptive using a
      survey design. Questionnaire data was collected from 127 adult patients with a
      diagnosis of cancer from both Scotland and England. CAM use was reported by 29%
      of the sample. The use of relaxation, meditation and the use of medicinal teas
      were the most frequently used therapies. Findings suggest that CAM use within
      patients diagnosed with cancer in the UK has increased which has implications for
      patient and health care professional education.

PMID- 15944107
TI  - Improving stressful working lives: complementary therapies, counselling and
      clinical supervision for staff.
AB  - The aim of this paper is to briefly examine the contemporary phenomenon of
      "burnout" within oncology and palliative care. In discussing the suitable
      interventions to manage stress and avoid burnout, reference will be made to
      counselling and clinical supervision, but more substantially the paper will
      report on an innovative subsidised complementary therapy service for staff. The
      Government's Improving Working Lives Standard will be referred as an initiative
      that supports the development of supportive services for NHS staff.

PMID- 15944108
TI  - Preliminary study of the lived experience of exercise for cancer survivors.
AB  - There is a growing body of evidence indicating the physical and psychosocial
      health benefits of exercising during cancer rehabilitation. However, physical
      activity levels of cancer survivors are generally low. This study adopted a
      qualitative approach to increase understanding of the lived experience of
      exercise for cancer survivors. Semi-structured interviews were carried out with
      six female cancer survivors who had taken part in the 2003 Race for Life
      fundraising event for Cancer Research UK. Following verbatim transcription of
      interviews, data reduction was carried out using Van Manen's method of thematic
      content analysis. Assimilation of central themes forms the basis of the final
      report. The essence of cancer survivors' experience of exercise was determined as
      'going forward'-to move on, physically and mentally following treatment, to
      rebuild social networks, and to restore a positive, confident outlook towards the
      future. The central theme of 'going forward' was identified in aspects of
      participants' physical and mental recovery, and their future intentions for
      exercise. Race for Life represented a positive focus for participants after
      cancer treatment, and proved to be an appropriate starting point for initiating,
      or returning to exercise following cancer. The results of the study support the
      suggestion that advice regarding exercise should be included in rehabilitation
      care for some cancer patients.

PMID- 15944109
TI  - Chair massage for carers in an acute cancer hospital.
AB  - The Chair Massage service considered in this evaluation study was provided to
      carers, visiting in-patients at a major cancer hospital in the UK. The two-stage
      evaluation comprised: firstly, a retrospective review of treatment records for
      the previous 12 months (n=182), and secondly, a prospective study, gathering data
      by interview and a 'next-day' questionnaire from carers (n=34), during 1 week of
      service delivery. The study at both stages sought to identify who used the
      service, post-treatment comments and changes in scores using a Feeling Good
      Thermometer (Field, T., 2000. Touch Therapy. Churchill Livingstone, London).
      During the second stage the carers were also asked about their concerns and
      worries, and to report changes in physical and emotional states using visual
      scales. Findings included significant improvements in physical and psychological
      scores; these were retained through to the next day. The next-day questionnaire
      also reported improved sleep for the majority of carers. A number of concerns and
      worries were raised at interview, notably anxieties about the patient and
      uncertainty about the future, family and financial worries. Overall, the service
      was well evaluated with parents and in particular female carers appearing to gain
      the most from the intervention.

PMID- 15944111
TI  - Soluble type A substance in fresh-frozen plasma as a function of ABO and Secretor
      genotypes and Lewis phenotype.
AB  - Soluble ABO blood group substance (SAS) in fresh-frozen plasma (FFP) and its
      cognate alloantibody titer reduction capacity (TRC) are not considered when
      prescribing this product for plasma exchange (PEX) therapy of ABO incompatible
      transplant recipients. SAS was quantified in 250 single FFPs using ELISA. Total
      and IgG class-specific anti-A TRCs of FFPs were measured using a
      microhemagglutination inhibition assay. SAS level depended not only on the A
      subtype (p < 0.0001) and the Secretor status (p < 0.0001), but also on the
      expression of ALe(b) in A1 secretors (p < 0.0001). The variation was as great as
      137.6 arbitrary units (aU) for 14 A1 Le(a-b-) secretors and 1.2 aU for 6 A2 non
      secretors. Homozygous expression of the A1, A2 and Secretor alleles did not
      increase SAS levels. Only total anti-A TRC, but not IgG class-specific TRC
      depended on the detected SAS level (r = 0.566, p = 0.0003).

PMID- 15944112
TI  - Immunoadsorption therapy and complement activation.
AB  - Complement activation was studied in six patients treated with immunoadsorption
      columns Ig-ADSOPAK for myasthenia gravis. Mean therapy duration was 18.6 months
      (range 4-28 months). Prior and after each procedure, concentrations of C3 and C4
      were examined, hemolytic activity of complement by a classic pathway (CH50) was
      determined, as well as terminal complement complex (TCC). After each
      immunoadsorption procedure, a decrease of C3 and C4 was noted (median 21.19% and
      19.68%, respectively). The CH50 and TCC follow-up showed statistically
      significant complement activation. Median of TCC accrual was 60.21% and median of
      CH50 decrease was 23.24%. No clinical manifestations of complement activation
      were present. With increasing number of procedures a marked decrease of TCC
      activation was observed in five patients, which was statistically significant in
      three of them (p < 0.05). This finding may indicate an immunomodulating effect of
      long-term adsorption therapy. With increasing number of procedures, an inhibition
      in complement system reactivity occurs. This result, however, has to be confirmed
      on a larger group of patients.

PMID- 15944113
TI  - Comparison of radioisotope methods and a non-radioisotope method to measure
      platelet survival in the baboon.
AB  - BACKGROUND: The in vivo survival of autologous fresh and preserved platelets can
      be measured using 51-Cr and 111-In-oxine radioisotope procedures and by a non
      radioisotope procedure using biotin-X-N-hydroxysuccinimide (NHS) with detection
      in the flow cytometer using fluorescent streptavidin. This study was done to
      assess the specificity of the radioisotopes 51-Cr and 111-In-oxine and non
      radioactive biotin-X-NHS to label platelets to measure their in vivo recovery and
      lifespan. STUDY DESIGN AND METHODS: In the study reported here, aliquots of
      autologous platelets from the same baboon were labeled with 51-Cr, 111-In oxine
      and biotin-X-NHS to measure platelet survival. Both cell-associated and platelet
      associated 51-Cr and 111-In oxine radioactivity were assessed to measure the in
      vivo recovery and lifespan of platelets. Blood volume was measured using the 125I
      albumin plasma volume and the total body hematocrit. RESULTS: In vivo recovery
      values measured during the 1-3h post-infusion period and during the 8 day post
      infusion period showed significant differences between the 51-Cr-labeled and the
      111-In-oxine labeled platelets. In the 51-Cr-labeled platelets, the cell
      associated radioactivity was about 50% higher than the platelet-associated
      radioactivity. In the 111-In-oxine labeled platelets, the cell-associated
      radioactivity was about 10% higher than the platelet-associated radioactivity.
      Similar in vivo recovery values were observed in the biotin-X-NHS labeled
      platelets and the 111-In-oxine labeled platelets assessed from the cell
      associated 111-In-radioactivity. CONCLUSION: The radioisotope 51-Cr and 111-In
      are non-specific labels for platelets, whereas biotin-X-NHS is a specific label
      for platelets identified in the flow cytometer with fluorescent streptavidin. The
      in vivo recovery values of autologous baboon platelets were similar when assessed
      from the cell-associated 111-In-oxine radioactivity and biotin-X-NHS labeled
      platelets.

PMID- 15944114
TI  - Haemapheresis activities in Germany.
AB  - Preparative and therapeutic haemaphereses are well established in Germany. Plasma
      and platelets are the most often collected products by apheresis. 1,090,329l of
      apheresed plasma were collected for fractionation in 2002. For therapeutic
      purposes 410,507 transfusion units (TUs) of plasma and 227,096 TUs of platelets
      were harvested by apheresis. The number of allogeneic and autologous peripheral
      blood stem cell collections is steadily increasing and supplants more and more
      the harvesting of bone marrow. There is only a small market for the collection of
      red blood cells (RBCs) by apheresis (4982 TUs in 2002) and multicomponent
      donation. Unfortunately, there is no central register for the data acquisition of
      therapeutic aphereses which makes it impossible to gain exact data about the
      number of performed procedures as well as their side effects. Preparative
      haemapheresis are usually carried out by specialists in Transfusion Medicine,
      whereas therapeutic aphereses are performed by experts in Transfusion Medicine
      and by clinicians of different specialties. Besides the well established
      plasmaphereses and cell depletions, new interesting therapeutic apheresis
      techniques, e.g. for the treatment of sudden hearing loss and cardiomyopathy, are
      promising.

PMID- 15944115
TI  - Multicomponent collection as of 2005.
AB  - Multicomponent apheresis (MCA) begun in Genoa in 1985 in autologous terms. Named
      "sequestration" it was the preoperative collection of autologous components (RBC
      plasma-platelets) using the same apparatus and harness ready for intraoperative
      blood salvage. In 1986 the technique was applied to donor platelet apheresis with
      the goal of reducing the costs of platelet collection and concurrently reducing
      the risks of viral disease transmission to haematological patients who did
      receive, in the same transfusion event, the necessary blood components obtained
      from the same donor. The results of this application were maximized by the so
      called aggressive MCA by which in selected donors, it is possible to collect 2
      units of platelets along with 1 or 2 units of PRBCs. These applications were made
      possible by the development of the concept of dry-platelet collection according
      to which platelets are collected in only 20-25 mL of plasma and subsequently
      resuspended in non-plasma solutions such as T-Sol. A last development of MCC is
      for RBC apheresis, with the collection of 1-2 units of RBC independently of
      platelet collection. This is going to be the first step of apheresis as the
      unique modality of collecting blood leaving the bags to history of blood
      transfusion. Interestingly it took 15 years to MCC to be rediscovered and
      appreciated worldwide both for its intrinsic cost saving capabilities offered
      along with an increasing safety for patients. In terms of donor acceptance it is
      our experience that, since 1989 no donor has refused MCC, consisting at least in
      the concurrent collection of plasma along with platelets, but also RBC and or a
      second unit of platelets.

PMID- 15944116
TI  - Multicomponent apheresis blood collection in the United States: current status
      and future directions.
AB  - Transfusion medicine in the USA confronts the ongoing challenges posed by a
      worsening blood supply, regulatory pressure, public pressure for increased safety
      and cost pressure. Multicomponent apheresis collection (MAC) is a powerful tool
      for addressing these issues. There are both clinical and operational advantages
      to MAC. The most important MAC procedures currently performed are platelet and
      two-red blood cell apheresis. Both procedures are growing in importance to the
      blood supply as the demand for platelets and red blood cells (RBC) increase. As
      the demand for safer and more standardized blood components increases, red cell
      apheresis may possibly become the collection standard.

PMID- 15944117
TI  - Two red blood cell units collected in SAG-M additive solution with the ALYX
      component collection system.
AB  - The first protocol available for the new ALYX component system (Baxter Healthcare
      Inc.) allows automated collection of two Red Blood Cell (RBC) units from one
      donor. The primary objective of our evaluation was to assess donor safety,
      comfort and to check the quality of blood products collected. 30 procedures were
      performed on eligible donors according to French best donation practices.
      Eligibility criteria were defined in order to ensure a post donation hemoglobin
      concentration of 11 g/dL minimum. Pre donation ferritin level was also checked.
      360 ml of absolute RBC were collected from each donor. Donors physiological
      parameters and haematological profile were measured immediately before and after
      donation. Adverse events and donors were observed during the procedure and
      followed daily during 5 days after donation. Hemolysis in RBC was followed until
      of shelf life (<0.8% on 42 days storage). The evaluation of different parameters
      during storage show no difference if we compare with the manual technique. The
      concentration of hemoglobin is good and all ou concentrates are conform. No
      serious adverse effects were reported during and after donation. All donors
      confirmed they would agree to donate 2 RBC units again with this system. We have
      seen a good quality of RBC products. This evaluation indicates that 2 RBC
      donation is feasible on the ALYX system, comfortable and safe for eligible
      donors.

PMID- 15944118
TI  - An unconventional role of neurotransmission in synapse formation.
AB  - How do presynaptic inputs regulate synapse formation? In this issue of Neuron,
      Lin et al. show that the neurotransmitter acetylcholine decreases the stability
      of AChR clusters. This dispersing activity, which requires the serine/threonine
      kinase Cdk5, cooperates with positive signals from motoneurons to ensure high
      concentration of AChRs at the neuromuscular junction.

PMID- 15944119
TI  - Reluctant vesicles coaxed into the limelight.
AB  - Synapses respond to brief, repetitive stimulation with synaptic depression when
      initial transmitter release probability is high. Vesicle depletion has been a
      long-standing hypothesis for depression, but results unexplained by the depletion
      hypothesis have been nagging. In this issue of Neuron, Xu and Wu show that, under
      some conditions, calcium current inactivation explains stimulus-dependent
      depression at the calyx of Held.

PMID- 15944120
TI  - Building neural choice points for love and war.
AB  - The molecular specification of central circuits that coordinate expression of
      innate behaviors in response to specific sensory cues from the environment
      remains a puzzle. In this issue of Neuron, Choi, Dong, and colleagues used
      expression profiling and genetic axonal tracing to visualize a hypothalamic point
      of convergence for defensive and reproductive olfactory cues that may function as
      a gating mechanism for sensory activation of defensive responses over
      reproduction.

PMID- 15944121
TI  - Expecting the unexpected: modeling of neuromodulation.
AB  - An important aspect of decision-making is the need to make interpretations and
      predictions in the face of uncertain information. In this issue of Neuron, Yu and
      Dayan describe a model of the role of acetylcholine and norepinephrine in
      balancing top-down expectation and bottom-up sensory input in guiding behavior.
      The model builds from data on physiological effects of modulators regulating the
      balance of cortical feedback and thalamic input.

PMID- 15944122
TI  - Dendritic spine geometry: functional implication and regulation.
AB  - Dendritic spines are tiny protrusions on dendritic shafts where most excitatory
      synapses are located. Recent advances in imaging technologies have given us great
      insight into the function of spines as biochemical compartments. Here we review
      recent evidence suggesting that the geometry of dendritic spines controls
      postsynaptic calcium signaling and is bidirectionally regulated during synaptic
      plasticity.

PMID- 15944123
TI  - S-nitrosylation of N-ethylmaleimide sensitive factor mediates surface expression
      of AMPA receptors.
AB  - Postsynaptic AMPA receptor (AMPAR) trafficking mediates some forms of synaptic
      plasticity that are modulated by NMDA receptor (NMDAR) activation and N
      ethylmaleimide sensitive factor (NSF). We report that NSF is physiologically S
      nitrosylated by endogenous, neuronally derived nitric oxide (NO). S-nitrosylation
      of NSF augments its binding to the AMPAR GluR2 subunit. Surface insertion of
      GluR2 in response to activation of synaptic NMDARs requires endogenous NO, acting
      selectively upon the binding of NSF to GluR2. Thus, AMPAR recycling elicited by
      NMDA neurotransmission is mediated by a cascade involving NMDA activation of
      neuronal NO synthase to form NO, leading to S-nitrosylation of NSF which is
      thereby activated, enabling it to bind to GluR2 and promote the receptor's
      surface expression.

PMID- 15944124
TI  - Presenilin-dependent transcriptional control of the Abeta-degrading enzyme
      neprilysin by intracellular domains of betaAPP and APLP.
AB  - Amyloid beta-peptide (Abeta), which plays a central role in Alzheimer's disease,
      is generated by presenilin-dependent gamma-secretase cleavage of beta-amyloid
      precursor protein (betaAPP). We report that the presenilins (PS1 and PS2) also
      regulate Abeta degradation. Presenilin-deficient cells fail to degrade Abeta and
      have drastic reductions in the transcription, expression, and activity of
      neprilysin, a key Abeta-degrading enzyme. Neprilysin activity and expression are
      also lowered by gamma-secretase inhibitors and by PS1/PS2 deficiency in mouse
      brain. Neprilysin activity is restored by transient expression of PS1 or PS2 and
      by expression of the amyloid intracellular domain (AICD), which is cogenerated
      with Abeta, during gamma-secretase cleavage of betaAPP. Neprilysin gene promoters
      are transactivated by AICDs from APP-like proteins (APP, APLP1, and APLP2), but
      not by Abeta or by the gamma-secretase cleavage products of Notch, N- or E-
      cadherins. The presenilin-dependent regulation of neprilysin, mediated by AICDs,
      provides a physiological means to modulate Abeta levels with varying levels of
      gamma-secretase activity.

PMID- 15944125
TI  - Light-dependent redistribution of arrestin in vertebrate rods is an energy
      independent process governed by protein-protein interactions.
AB  - In rod photoreceptors, arrestin localizes to the outer segment (OS) in the light
      and to the inner segment (IS) in the dark. Here, we demonstrate that
      redistribution of arrestin between these compartments can proceed in ATP-depleted
      photoreceptors. Translocation of transducin from the IS to the OS also does not
      require energy, but depletion of ATP or GTP inhibits its reverse movement. A
      sustained presence of activated rhodopsin is required for sequestering arrestin
      in the OS, and the rate of arrestin relocalization to the OS is determined by the
      amount and the phosphorylation status of photolyzed rhodopsin. Interaction of
      arrestin with microtubules is increased in the dark. Mutations that enhance
      arrestin-microtubule binding attenuate arrestin translocation to the OS. These
      results indicate that the distribution of arrestin in rods is controlled by its
      dynamic interactions with rhodopsin in the OS and microtubules in the IS and that
      its movement occurs by simple diffusion.

PMID- 15944126
TI  - Neurotransmitter acetylcholine negatively regulates neuromuscular synapse
      formation by a Cdk5-dependent mechanism.
AB  - Synapse formation requires interactions between pre- and postsynaptic cells to
      establish the connection of a presynaptic nerve terminal with the
      neurotransmitter receptor-rich postsynaptic apparatus. At developing vertebrate
      neuromuscular junctions, acetylcholine receptor (AChR) clusters of nascent
      postsynaptic apparatus are not apposed by presynaptic nerve terminals. Two
      opposing activities subsequently promote the formation of synapses: positive
      signals stabilize the innervated AChR clusters, whereas negative signals disperse
      those that are not innervated. Although the nerve-derived protein agrin has been
      suggested to be a positive signal, the negative signals remain elusive. Here, we
      show that cyclin-dependent kinase 5 (Cdk5) is activated by ACh agonists and is
      required for the ACh agonist-induced dispersion of the AChR clusters that have
      not been stabilized by agrin. Genetic elimination of Cdk5 or blocking ACh
      production prevents the dispersion of AChR clusters in agrin mutants. Therefore,
      we propose that ACh negatively regulates neuromuscular synapse formation through
      a Cdk5-dependent mechanism.

PMID- 15944127
TI  - The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic
      transmission at the C. elegans neuromuscular junction.
AB  - Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate
      nervous system, underlies nicotine addiction, and nicotinic receptor dysfunction
      leads to neurological disorders. The C. elegans neuromuscular junction (NMJ)
      shares many characteristics with neuronal synapses, including multiple classes of
      postsynaptic currents. Here, we identify two genes required for the major
      excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic
      AChR subunit homologous to the vertebrate alpha7 subunit, and cam-1, which
      encodes a Ror receptor tyrosine kinase. acr-16 mutants lack fast cholinergic
      current at the NMJ and exhibit synthetic behavioral deficits with other known
      AChR mutants. In cam-1 mutants, ACR-16 is mislocalized and ACR-16-dependent
      currents are disrupted. The postsynaptic deficit in cam-1 mutants is accompanied
      by alterations in the distribution of cholinergic vesicles and associated
      synaptic proteins. We hypothesize that CAM-1 contributes to the localization or
      stabilization of postsynaptic ACR-16 receptors and presynaptic release sites.

PMID- 15944128
TI  - Nicotine upregulates its own receptors through enhanced intracellular maturation.
AB  - Chronic exposure to nicotine elicits upregulation of high-affinity nicotinic
      receptors in the smoker's brain. To address the molecular mechanism of
      upregulation, we transfected HEK293 cells with human alpha4beta2 receptors and
      traced the subunits throughout their intracellular biosynthesis, using metabolic
      labeling and immunoprecipitation techniques. We show that high-mannose
      glycosylated subunits mature and assemble into pentamers in the endoplasmic
      reticulum and that only pentameric receptors reach the cell surface following
      carbohydrate processing. Nicotine is shown to act inside the cell and to increase
      the amount of beta subunits immunoprecipitated by the conformation-dependent
      mAb290, indicating that nicotine enhances a critical step in the intracellular
      maturation of these receptors. This effect, which also takes place at
      concentrations of nicotine found in the blood of smokers upon expression of
      alpha4beta2 in SH-SY5Y neuroblastoma cells, may play a crucial role in nicotine
      addiction and possibly implement a model of neural plasticity.

PMID- 15944129
TI  - Spine-neck geometry determines NMDA receptor-dependent Ca2+ signaling in
      dendrites.
AB  - Increases in cytosolic Ca2+ concentration ([Ca2+]i) mediated by NMDA-sensitive
      glutamate receptors (NMDARs) are important for synaptic plasticity. We studied a
      wide variety of dendritic spines on rat CA1 pyramidal neurons in acute
      hippocampal slices. Two-photon uncaging and Ca2+ imaging revealed that NMDAR
      mediated currents increased with spine-head volume and that even the smallest
      spines contained a significant number of NMDARs. The fate of Ca2+ that entered
      spine heads through NMDARs was governed by the shape (length and radius) of the
      spine neck. Larger spines had necks that permitted greater efflux of Ca2+ into
      the dendritic shaft, whereas smaller spines manifested a larger increase in
      [Ca2+]i within the spine compartment as a result of a smaller Ca2+ flux through
      the neck. Spine-neck geometry is thus an important determinant of spine Ca2+
      signaling, allowing small spines to be the preferential sites for isolated
      induction of long-term potentiation.

PMID- 15944130
TI  - Decreases in CaMKII activity trigger persistent potentiation of intrinsic
      excitability in spontaneously firing vestibular nucleus neurons.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) has been described as a
      biochemical switch that is turned on by increases in intracellular calcium to
      mediate synaptic plasticity. Here, we show that reductions in CaMKII activity
      trigger persistent increases in intrinsic excitability. In spontaneously firing
      vestibular nucleus neurons, CaMKII activity is near maximal, and blockade of
      CaMKII activity increases excitability by reducing BK-type calcium-activated
      potassium currents. Firing rate potentiation, a form of plasticity in which
      synaptic inhibition induces long-lasting increases in excitability, is occluded
      by prior blockade of CaMKII and blocked by addition of constitutively active
      CaMKII. Reductions in CaMKII activity are necessary and sufficient to induce
      firing rate potentiation and may contribute to motor learning in the vestibulo
      ocular reflex.

PMID- 15944131
TI  - The decrease in the presynaptic calcium current is a major cause of short-term
      depression at a calyx-type synapse.
AB  - Repetitive nerve firings cause short-term depression (STD) of release at many
      synapses. Its underlying mechanism is largely attributed to depletion of a
      readily releasable vesicle pool (RRP) and a decreased probability of releasing a
      readily releasable vesicle during an action potential. Which of these two
      mechanisms is dominant and the mechanism that decreases the release probability
      remain debated. Here, we report that a decreased release probability is caused by
      a calcium-induced inhibition of presynaptic calcium channels, particularly P/Q
      type channels at the calyx of Held in rat brainstem. This mechanism was the
      dominant cause of STD in a wide range of stimulation conditions, such as during 2
      to 20 action potential-equivalent stimuli (AP-e) at 0.2-30 Hz and after 2 to 20
      AP-e at 0.2-100 Hz. Only during > or = 100 Hz AP-e was depletion the dominant
      mechanism.

PMID- 15944132
TI  - Lhx6 delineates a pathway mediating innate reproductive behaviors from the
      amygdala to the hypothalamus.
AB  - In mammals, innate reproductive and defensive behaviors are mediated by
      anatomically segregated connections between the amygdala and hypothalamus. This
      anatomic segregation poses the problem of how the brain integrates activity in
      these circuits when faced with conflicting stimuli eliciting such mutually
      exclusive behaviors. Using genetically encoded and conventional axonal tracers,
      we have found that the transcription factor Lhx6 delineates the reproductive
      branch of this pathway. Other Lhx proteins mark neurons in amygdalar nuclei
      implicated in defense. We have traced parallel projections from the posterior
      medial amygdala, activated by reproductive or defensive olfactory stimuli,
      respectively, to a point of convergence in the ventromedial hypothalamus. The
      opposite neurotransmitter phenotypes of these convergent projections suggest a
      "gate control" mechanism for the inhibition of reproductive behaviors by
      threatening stimuli. Our data therefore identify a potential neural substrate for
      integrating the influences of conflicting behavioral cues and a transcription
      factor family that may contribute to the development of this substrate.

PMID- 15944133
TI  - Extinction of cocaine self-administration reveals functionally and temporally
      distinct dopaminergic signals in the nucleus accumbens.
AB  - While Pavlovian and operant conditioning influence drug-seeking behavior, the
      role of rapid dopamine signaling in modulating these processes is unknown. During
      self-administration of cocaine, two dopaminergic signals, measured with 100 ms
      resolution, occurred immediately before and after the lever press (termed pre-
      and post-response dopamine transients). Extinction of self-administration
      revealed that these two signals were functionally distinct. Pre-response
      transients, which could reflect the motivation to obtain the drug, did not
      decline during extinction. Remarkably, post-response dopamine transients
      attenuated as extinction progressed, suggesting that they encode the learned
      association between environmental cues and cocaine. A third type of dopamine
      transient, not time locked to overt stimuli, decreased in frequency during
      extinction and correlated with calculated cocaine concentrations. These results
      show that dopamine release transients involved in different aspects of cocaine
      self-administration are highly plastic--differentially governed by motivation,
      learned associations linked with environmental stimuli, and the pharmacological
      actions of cocaine.

PMID- 15944134
TI  - Cognitive modulation of olfactory processing.
AB  - We showed how cognitive, semantic information modulates olfactory representations
      in the brain by providing a visual word descriptor, "cheddar cheese" or "body
      odor," during the delivery of a test odor (isovaleric acid with cheddar cheese
      flavor) and also during the delivery of clean air. Clean air labeled "air" was
      used as a control. Subjects rated the affective value of the test odor as
      significantly more unpleasant when labeled "body odor" than when labeled "cheddar
      cheese." In an event-related fMRI design, we showed that the rostral anterior
      cingulate cortex (ACC)/medial orbitofrontal cortex (OFC) was significantly more
      activated by the test stimulus and by clean air when labeled "cheddar cheese"
      than when labeled "body odor," and the activations were correlated with the
      pleasantness ratings. This cognitive modulation was also found for the test odor
      (but not for the clean air) in the amygdala bilaterally.

PMID- 15944135
TI  - Uncertainty, neuromodulation, and attention.
AB  - Uncertainty in various forms plagues our interactions with the environment. In a
      Bayesian statistical framework, optimal inference and prediction, based on
      unreliable observations in changing contexts, require the representation and
      manipulation of different forms of uncertainty. We propose that the
      neuromodulators acetylcholine and norepinephrine play a major role in the brain's
      implementation of these uncertainty computations. Acetylcholine signals expected
      uncertainty, coming from known unreliability of predictive cues within a context.
      Norepinephrine signals unexpected uncertainty, as when unsignaled context
      switches produce strongly unexpected observations. These uncertainty signals
      interact to enable optimal inference and learning in noisy and changeable
      environments. This formulation is consistent with a wealth of physiological,
      pharmacological, and behavioral data implicating acetylcholine and norepinephrine
      in specific aspects of a range of cognitive processes. Moreover, the model
      suggests a class of attentional cueing tasks that involve both neuromodulators
      and shows how their interactions may be part-antagonistic, part-synergistic.

PMID- 15944136
TI  - Gene expression profiling of Lewy body-bearing neurons in Parkinson's disease.
AB  - Lewy bodies (LB) are a pathological hallmark of Parkinson's disease (PD). Whether
      LBs are neuroprotective, cytotoxic, or an age-related epiphenomenon is still
      debated. In the present study, the genetic fingerprints of mesencephalic
      dopaminergic (DA) neurons containing LBs versus mesencephalic DA neurons not
      containing LBs were compared in five PD patients. Total RNA from single neurons
      of both neuronal subpopulations was obtained by immuno-laser capture
      microdissection. Subsequently, RNA arbitrarily primed PCR was employed to
      generate expression profiles from the extracted RNA. Differentially displayed
      polymorphic fragments were dissected from silver-stained polyacrylamide gels.
      Most of these expressed sequence tags (ESTs) were homologous to known human
      sequences (56/64, 87.5%). Based on the potential significance of individual ESTs
      in neurodegenerative disorders, 5 ESTs of interest were selected for further
      quantitative expression analysis by real-time quantitative reverse transcription
      PCR (rtq RT-PCR). DA neurons without LBs preferentially expressed molecules
      beneficial for cell survival, whereas genes preferentially expressed in DA
      neurons containing LBs may support a cytotoxic role of LBs. Thus, we favor the
      view that LB-positive DA neurons are sicker than their LB-negative counterparts,
      and that inhibition of LB formation may indeed represent a therapeutic strategy
      in PD.

PMID- 15944137
TI  - Sleep disturbances in Japanese patients with Parkinson's disease--comparing with
      patients in the UK.
AB  - Sleep disorders are common in the general population and occur more frequently
      with advancing age. However, patients with Parkinson's disease (PD) have been
      known to have various sleep disturbances beyond those to be expected from the
      effect of aging alone. We tried to quantify the various aspects of nocturnal
      sleep problems in PD using the PD sleep scale (PDSS). 64 patients with PD and 60
      age- and sex-matched controls completed the PDSS. After neurological
      examinations, we assessed the degree of sleep disorder by the PDSS. We evaluated
      the severity of PD by the Hoehn and Yahr Scale and the unified PD rating scale
      (UPDRS). To compare the various aspects of nocturnal sleep problems in PD between
      in Japan and in the United Kingdom (UK), we referenced and compared our results
      with those by Chaudhui et al. The PDSS scores in PD group were significantly
      different from those in controls. Individual items of the scale showed good
      discriminatory power between PD and controls. Overall tendencies were the same in
      Japan and in the UK, but there were some different points, especially absence of
      refreshing quality of sleep in Japan. We believe that the PDSS provides an
      objective method for targeted therapeutic approaches for the treatment of
      disturbed sleep in PD even among countries with different cultures, such as Japan
      and the UK.

PMID- 15944138
TI  - Gender, suicidality and bipolar mixed states in adolescents.
AB  - BACKGROUND: The purpose of this study was to determine the relationship between
      mixed states and suicidality among adolescent outpatients presenting with a DSM
      IV defined major depressive episode (MDE). METHODS: Two-hundred and forty-seven
      adolescents meeting the criteria for MDE were screened for the presence of
      concurrent, intra-MDE hypomania/mania (i.e., mixed states). All patients were
      asked whether they had current suicidal ideation or had recently attempted any
      self-destructive physical act associated with the thought of dying (i.e., a
      suicide attempt). The data were subjected to analysis using univariate logistic
      regression. RESULTS: One hundred of the 247 (40.5%) adolescents were bipolar type
      I or type II. Of these, 82% were in mixed states. Of the patients with suicidal
      ideation, 62.8% were girls, and of those with histories of a suicide attempt,
      69.4% were girls. Girls had more than twice the risk of having suicidal ideation
      (OR=2.2, p=0.004) and nearly 3 times the risk of having histories of a suicide
      attempt than boys (OR=2.87, p<0.0001). Being in a mixed state per se did not
      predict either suicidal ideation or a suicide attempt among all of the 247
      patients. However, mixed states apparently independently contributed to the risk
      of (non-fatal) suicidal behavior among girls only. Of the mixed states, girls had
      nearly 4 times the risk of having made a suicide attempt compared with those
      without mixed states (OR=3.9, p=0.003). Age, presence of psychotic features and
      family history of mood disorder had little or no bearing on suicidality.
      LIMITATIONS: Correlational chart review study, no data collection on Axis I and
      Axis II comorbidity and adverse life-events. CONCLUSIONS: This report of greater
      suicidality in adolescent girls in a mixed state parallels the well-known adult
      literature of high frequency of mixed states in women. The findings are of
      relevance to the controversy of antidepressants and suicidality in juvenile
      depressives in that they identify a vulnerable group. In line with earlier
      suggestions by the senior author [Akiskal, H.S., 1995. Developmental pathways to
      bipolarity: are juvenile-onset depressions pre-bipolar? J. Am. Acad. Child
      Adolesc. Psych. 34, 754-763], our data highlight the public health importance of
      the wider recognition of bipolar mixed states in juvenile patients masquerading
      as unipolar depression. Finally, it appears to us that it is the failure of our
      formal nosology on mixed states--rather than the antidepressants per se--which is
      the root problem in this controversy.

PMID- 15944139
TI  - Saliva versus serum estradiol: implications for research studies using
      postmenopausal women.
AB  - OBJECTIVE: The authors investigated saliva as a potentially reliable medium for
      estradiol (E2) measurements in postmenopausal women. The goal of this study was
      to determine whether or not saliva could be used in studies of postmenopausal
      women in place of serum samples. Specifically, the authors wondered whether or
      not saliva and serum E2, obtained simultaneously from samples collected from
      postmenopausal women, would correlate. DESIGN: Samples of saliva and serum were
      collected simultaneously from 43 postmenopausal women. 31 were regular users of
      estrogen therapy (ET), 12 used no ET. Pearson's correlation coefficients were
      conducted to determine the degree of relationship between saliva and serum
      samples among ET users and non-users. RESULTS: Among ET users saliva and serum E2
      levels were significantly and positively correlated (r = 0.81, p < 0.0001). The
      two E2 values were not significantly correlated among ET non-users (r = 0.32, p <
      0.31). CONCLUSIONS: These data suggest that saliva E2 may be a fairly robust
      predictor of serum E2, but only among postmenopausal women who use ET.

PMID- 15944140
TI  - Comparative genomics of bidirectional gene pairs and its implications for the
      evolution of a transcriptional regulation system.
AB  - Arrangement of genes in the human genome was not considered to be ordered like
      those of prokaryotes, as in many cases genes appeared to be randomly distributed
      across the genome. However, by focusing on the closely located adjacent gene
      pairs, it was recently suggested that the bidirectional pairs were enriched in
      the human genome and these pairs tended to be coexpressed by sharing promoter
      sequences. We compared this biased organization found in the human genome with
      those in the genomes of nine other eukaryotes to reveal when and how the biased
      organization had evolved using a total of 122,945 adjacent gene pairs. As a
      result, we found that the biased organization was found only in mammals, and not
      in other eukaryotes. Interestingly, we found that many of these genes in the
      bidirectional arrangement were not mammalian specific genes but conserved among
      various animals. Further analyses revealed that the bidirectional arrangement of
      these pairs had arisen by utilizing already-existing genes in the lineage leading
      to mammals recently, no earlier than the vertebrate-ascidian divergence. Since
      the novel bidirectional arrangement could result in novel co-regulated
      transcription, our results here provide evidence that shows how a transcriptional
      regulation system has evolved through changes in the genome organization,
      especially in the lineage leading to humans.

PMID- 15944141
TI  - Auditory P300 in high-risk, recent-onset and chronic schizophrenia.
AB  - BACKGROUND: The present study examined the integrity of the P300 component of the
      event-related potential (ERP) in patients at high imminent risk for schizophrenia
      in relation to healthy comparison subjects and patients in the recent-onset and
      chronic stages of schizophrenia. METHODS: The P300 was recorded by using an
      auditory oddball task in 10 patients clinically considered at risk of being
      prodromally symptomatic for schizophrenia, 10 patients with recent-onset
      schizophrenia, 14 patients with chronic schizophrenia, 14 young healthy
      comparison subjects, who were age-matched to the high-risk and recent-onset
      schizophrenia groups, and 14 older healthy comparison subjects, who were age
      matched to the chronic schizophrenia group. RESULTS: High-risk subjects displayed
      smaller than normal P300 amplitudes at the parietal, centroparietal and central
      scalp locations. The observed P300 amplitude abnormalities in high-risk subjects
      were severe, being comparable in magnitude to the abnormalities seen in recent
      onset and chronic schizophrenia subjects. However, whereas high-risk subjects
      showed P300 amplitude abnormalities that were bilaterally symmetrical, subjects
      with recent-onset schizophrenia and, particularly, subjects with chronic
      schizophrenia exhibited abnormalities that were markedly larger over the left
      temporal scalp sites. CONCLUSIONS: Patients at high imminent risk for developing
      a first florid psychotic episode seem to manifest auditory P300 amplitude
      abnormalities that are similar, but not identical, to those observed in patients
      in the recent-onset and chronic stages of schizophrenia. These results support
      the idea that auditory P300 abnormalities in schizophrenia reflect a primary
      cognitive and pathophysiological feature of the illness.

PMID- 15944142
TI  - The serotonin-1Dbeta receptor gene and severity of obsessive-compulsive disorder
      in women with bulimia nervosa.
AB  - BACKGROUND: There is significant evidence that eating disorders have an important
      biological overlap with obsessive-compulsive disorder (OCD), though the specific
      mediators of this relationship remain unclear. Recent evidence suggests that the
      G861C polymorphism of the 5HT-1Dbeta receptor gene and the G allele in particular
      may play a role in OCD. We thus hypothesized that, among a heterogenous group of
      probands with bulimia nervosa (BN), this same G allele might predict the presence
      and/or severity of OCD pathology. METHODS: 165 consecutive female probands with
      BN were genotyped for the G861C polymorphism of the 5HT-1Dbeta receptor gene.
      Rates of full syndrome OCD, partial syndrome OCD and no OCD were compared across
      the three genotypic groups defined by this polymorphism. RESULTS: 45 out of 165
      BN probands (27.3%) had either full or partial syndrome OCD. In the full sample,
      there was a significant difference in the distribution of the three diagnostic
      groups by genotype (chi2=10.07, df=4, p=.039). The G861C polymorphism did not
      strongly predict which probands had any vs. no OCD pathology. However, among the
      45 probands with OCD symptoms, the G861C polymorphism did strongly differentiate
      full syndrome vs. partial syndrome OCD (chi2=9.26, df=2, p=.01; odds ratio for
      full syndrome OCD with GG genotype=7.69, 95% CI=1.45-40.9). DISCUSSION: In women
      with BN, the G861C polymorphism of the 5HT-1Dbeta gene does not appear to be
      associated with the generation of OCD symptoms; however, it might directly or
      indirectly be associated with a modulatory effect on syndrome severity in
      probands otherwise predisposed to OCD. While preliminary and in need of
      replication in other samples, this is the first association study to suggest how
      a particular gene might influence OCD pathology in an eating disorder population.

PMID- 15944143
TI  - Effects of alphabeticality, practice and type of instruction on reading an
      artificial script: an fMRI study.
AB  - In neuroimaging studies of word reading in natural scripts, the effect of
      alphabeticality is often confounded with the effect of practice. We used an
      artificial script to separately manipulate the effects of practice and
      alphabeticality following training with and without explicit letter instructions.
      Participants received multi-session training in reading nonsense words, written
      in an artificial script, wherein each phoneme was represented by 2 discrete
      symbols . Three training conditions were compared: alphabetical whole words with
      letter decoding instruction (explicit); alphabetical whole-words (implicit) and
      non-alphabetical whole-words (arbitrary). Each participant was trained on the
      arbitrary condition and on one of the alphabetical conditions (explicit or
      implicit). fMRI scans were acquired after training during reading of trained
      words and relatively novel words in the alphabetical and arbitrary conditions.
      Our results showed greater activation in the explicit compared to the arbitrary
      conditions, but only for relatively-novel words, in the left posterior inferior
      frontal gyrus (IFG). In the implicit condition, the left posterior IFG was active
      in both trained and relatively novel words. These results indicate the
      involvement of the left posterior IFG in letter decoding, and suggest that
      reading of explicitly well-trained words did not rely on letter decoding, while
      in implicitly trained words letter decoding persisted into later stages. The
      superior parietal lobules showed reduced activation for items that received more
      practice, across all training conditions. Altogether, our results suggest that
      the alphabeticality of the word, the amount of practice and type of instructions
      have independent and interacting effects on brain activation during reading.

PMID- 15944144
TI  - Anomalous indoor radon concentration in a dwelling in Qatif City, Saudi Arabia.
AB  - An indoor radon survey was carried out recently in nine cities of Saudi Arabia
      using nuclear track detectors (NTD)-based passive radon detectors. The survey
      included Qatif City in the Eastern Province of Saudi Arabia, where 225 detectors
      were collected back successfully. It was found that the average indoor radon
      concentration in the dwellings was 22 +/- 15 Bq m(-3). However, one of the
      dwellings showed an anomalous radon concentration of 535 +/- 23 Bq m(-3). This
      finding led to a detailed investigation of this dwelling using active and passive
      techniques. In the active technique, an AlphaGUARD 2000 PRQ radon gas analyser
      was used. In the passive technique, CR-39 based passive radon detectors were used
      in all the rooms of the dwelling. Radon exhalation from the wall and the floor
      was also measured using the can technique. The active measurement confirms the
      passive one. Before placing the passive radon detectors in all the rooms of the
      two-storey building, the inhabitant was advised to ventilate his house regularly.
      The radon concentration in the different rooms was found to vary from 124 to 302
      Bq m(-3). Radon exhalation from the floor and the wall of the room with the
      anomalous radon concentration was found to vary from 0.5 to 0.8 Bq m(-2) h(-1).
      These low radon exhalation rates suggest that the anomalous radon concentration
      is most probably due to underground radon diffusion into the dwelling through
      cracks and joints in the concrete floor.

PMID- 15944145
TI  - Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization
      and reducing MafA expression in isolated rat islets of Langerhans.
AB  - Abnormalities in lipid metabolism have been proposed as contributing factors to
      both defective insulin secretion from the pancreatic beta cell and peripheral
      insulin resistance in type 2 diabetes. Previously, we have shown that prolonged
      exposure of isolated rat islets of Langerhans to excessive fatty acid levels
      impairs insulin gene transcription. This study was designed to assess whether
      palmitate alters the expression and binding activity of the key regulatory
      factors pancreas-duodenum homeobox-1 (PDX-1), MafA, and Beta2, which respectively
      bind to the A3, C1, and E1 elements in the proximal region of the insulin
      promoter. Nuclear extracts of isolated rat islets cultured with 0.5 mm palmitate
      exhibited reduced binding activity to the A3 and C1 elements but not the E1
      element. Palmitate did not affect the overall expression of PDX-1 but reduced its
      nuclear localization. In contrast, palmitate blocked the stimulation of MafA mRNA
      and protein expression by glucose. Combined adenovirus-mediated overexpression of
      PDX-1 and MafA in islets completely prevented the inhibition of insulin gene
      expression by palmitate. These results demonstrate that prolonged exposure of
      islets to palmitate inhibits insulin gene transcription by impairing nuclear
      localization of PDX-1 and cellular expression of MafA.

PMID- 15944146
TI  - Platelet-derived growth factor receptor-beta (PDGFR-beta) activation promotes its
      association with the low density lipoprotein receptor-related protein (LRP).
      Evidence for co-receptor function.
AB  - Activation of the platelet-derived growth factor receptor-beta (PDGFR-beta) leads
      to tyrosine phosphorylation of the cytoplasmic domain of LRP and alters its
      association with adaptor and signaling proteins, such as Shc. The mechanism of
      the PDGF-induced LRP tyrosine phosphorylation is not well understood, especially
      since PDGF not only activates PDGF receptor but also binds directly to LRP. To
      gain insight into this mechanism, we used a chimeric receptor in which the ligand
      binding domain of the PDGFR-beta was replaced with that from the macrophage
      colony-stimulating factor (M-CSF) receptor, a highly related receptor tyrosine
      kinase of the same subfamily, but with different ligand specificity. Activation
      of the chimeric receptor upon the addition of M-CSF readily mediated the tyrosine
      phosphorylation of LRP. Since M-CSF is not recognized by LRP, these results
      indicated that growth factor binding to LRP is not necessary for this
      phosphorylation event. Using a panel of cytoplasmic domain mutants of the
      chimeric M-CSF/PDGFR-beta, we confirmed that the kinase domain of PDGFR-beta is
      absolutely required for LRP tyrosine phosphorylation but that PDGFR-beta-mediated
      activation of phosphatidylinositol 3-kinase, RasGAP, SHP-2, phospholipase C
      gamma, and Src are not necessary for LRP tyrosine phosphorylation. To identify
      the cellular compartment where LRP and the PDGFR-beta may interact, we employed
      immunofluorescence and immunogold electron microscopy. In WI-38 fibroblasts,
      these two receptors co-localized in coated pits and endosomal compartments
      following PDGF stimulation. Further, phosphorylated forms of the PDGFR-beta co
      immunoprecipitated with LRP following PDGF treatment. Together, these studies
      revealed close association between activated PDGFR-beta and LRP, suggesting that
      LRP functions as a co-receptor capable of modulating the signal transduction
      pathways initiated by the PDGF receptor from endosomes.

PMID- 15944147
TI  - Molecular definition of a novel inositol polyphosphate metabolic pathway
      initiated by inositol 1,4,5-trisphosphate 3-kinase activity in Saccharomyces
      cerevisiae.
AB  - The production of inositol polyphosphate (IPs) and pyrophosphates (PP-IPs) from
      inositol 1,4,5-trisphosphate (I(1,4,5)P3) requires the 6-/3-/5-kinase activity of
      Ipk2 (also known as Arg82 and inositol polyphosphate multikinase). Here, we
      probed the distinct roles for I(1,4,5)P3 6- versus 3-kinase activities in IP
      metabolism and cellular functions reported for Ipk2. Expression of either
      I(1,4,5)P3 6- or 3-kinase activity rescued growth of ipk2-deficient yeast at high
      temperatures, whereas only 6-kinase activity enabled growth on ornithine as the
      sole nitrogen source. Analysis of IP metabolism revealed that the 3-kinase
      initiated the synthesis of novel pathway consisting of over eleven IPs and PP
      IPs. This pathway was present in wild-type and ipk2 null cells, albeit at low
      levels as compared with inositol hexakisphosphate synthesis. The primary route of
      synthesis was: I(1,4,5)P3 --> I(1,3,4,5)P4 --> I(1,2,3,4,5)P5 --> PP-IP4 --> PP2
      IP3 and required Kcs1 (or possibly Ipk2), Ipk1, a novel inositol pyrophosphate
      synthase, and then Kcs1 again, respectively. Mutation of kcs1 ablated this
      pathway in ipk2 null cells and overexpression of Kcs1 in ipk2 mutant cells
      phenocopied IP3K expression, confirming it harbors a novel 3-kinase activity. Our
      work provides a revised genetic map of IP metabolism in yeast and evidence for
      dosage compensation between IPs and PP-IPs downstream of I(1,4,5)P3 in the
      regulation of nucleocytoplasmic processes.

PMID- 15944148
TI  - Positive regulation of sugar catabolic pathways in the cyanobacterium
      Synechocystis sp. PCC 6803 by the group 2 sigma factor sigE.
AB  - The sigE gene of Synechocystis sp. PCC 6803 encodes a group 2 sigma factor for
      RNA polymerase and has been proposed to function in transcriptional regulation of
      nitrogen metabolism. By using microarray and Northern analyses, we demonstrated
      that the abundance of transcripts derived from genes important for glycolysis,
      the oxidative pentose phosphate pathway, and glycogen catabolism is reduced in a
      sigE mutant of Synechocystis maintained under the normal growth condition.
      Furthermore, the activities of the two key enzymes of the oxidative pentose
      phosphate pathway, glucose-6-phosphate dehydrogenase and 6-phosphogluconate
      dehydrogenase, encoded by the zwf and gnd genes were also reduced in the sigE
      mutant. The dark enhancements in both enzyme activity and transcript abundance
      apparent in the wild type were eliminated by the mutation. In addition, the sigE
      mutant showed a reduced rate of glucose uptake and an increased intracellular
      level of glycogen. Moreover, it was unable to proliferate under the light
      activated heterotrophic growth conditions. These results indicate that SigE
      functions in the transcriptional activation of sugar catabolic pathways in
      Synechocystis sp. PCC 6803.

PMID- 15944149
TI  - Investigation of the lateral light-induced migration of photosystem II light
      harvesting proteins by nano-high performance liquid chromatography electrospray
      ionization mass spectrometry.
AB  - This study reports a detailed analysis of the light-induced lateral migration of
      the photosystem II (PSII) antennae between appressed and non-appressed thylakoid
      membranes. The relative PSII antennae that migrated to stroma lamellae were
      readily established on the basis of peak areas of the separated stroma proteins
      in the ultraviolet chromatograms. Phosphorylation was predicted by intact
      molecular mass measurements, and this was confirmed by immunoblotting. When
      thylakoid membrane and chloroplasts were illuminated at 100 microE m(-2)s(-1),
      light-harvesting complex type II (Lhcb2) was the first PSII antenna to migrate,
      preferentially in phosphorylated form. However, the amount of Lhcb2 that migrated
      decreased after the first 20 min when the total amount of the three different
      Lhcb1 isoforms (1.1, 1.2, and 1.3) reached maximum. Lhcb1.1 was always found in
      the unphosphorylated form and migrated later than the other two isoforms,
      although the latter were also found to have low levels of phosphorylation. At the
      same time, major antennae on the grana were not found to be phosphorylated,
      whereas Lhcb4 showed a significant increase in molecular mass. At higher light
      intensity Lhcb2 migration was negligible, whereas migration of Lhcb1 isoforms was
      little changed, increasing in irradiated chloroplasts. Because there was no
      significant phosphorylation at high light intensity, and yet pigments were found
      to have significantly increased on the stroma lamellae, it may be that pigments
      play a role in migration and that, in fact, there is no direct correlation
      between phosphorylation and migration. We hypothesize that the Lhcb1 isoforms
      expressed by the multigene families play a role in plant adaptation.

PMID- 15944150
TI  - Mutations in MTO2 related to tRNA modification impair mitochondrial gene
      expression and protein synthesis in the presence of a paromomycin resistance
      mutation in mitochondrial 15 S rRNA.
AB  - Nuclear gene(s) have been shown to modulate the phenotypic expression of
      mitochondrial DNA mutations. We report here the identification and
      characterization of the yeast nuclear gene MTO2 encoding an evolutionarily
      conserved protein involved in mitochondrial tRNA modification. Interestingly,
      mto2 null mutants expressed a respiratory-deficient phenotype when coexisting
      with the C1409G mutation of mitochondrial 15 S rRNA at the very conservative site
      for human deafness-associated 12 S rRNA A1491G and C1409T mutations. Furthermore,
      the overall rate of mitochondrial translation was markedly reduced in a yeast
      mto2 strain in the wild type mitochondrial background, whereas mitochondrial
      protein synthesis was almost abolished in a yeast mto2 strain carrying the C1409G
      allele. The other interesting feature of mto2 mutants is the defective expression
      of mitochondrial genes, especially CYTB and COX1, but only when coexisting with
      the C1409G allele. These data strongly indicate that a product of MTO2
      functionally interacts with the decoding region of 15 S rRNA, particularly at the
      site of the C1409G or A1491G mutation. In addition, we showed that yeast and
      human Mto2p localize in mitochondria. The isolated human MTO2 cDNA can partially
      restore the respiratory-deficient phenotype of yeast mto2 cells carrying the
      C1409G mutation. These functional conservations imply that human MTO2 may act as
      a modifier gene, modulating the phenotypic expression of the deafness-associated
      A1491G or C1409T mutation in mitochondrial 12 S rRNA.

PMID- 15944151
TI  - Inhibition of activator protein-1, NF-kappaB, and MAPKs and induction of phase 2
      detoxifying enzyme activity by chlorogenic acid.
AB  - Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most
      abundant polyphenols in the human diet. The antioxidant and anticarcinogenic
      properties of chlorogenic acid have been established in animal studies. However,
      little is known about the molecular mechanisms through which chlorogenic acid
      inhibits carcinogenesis. In this study, we found that chlorogenic acid inhibited
      the proliferation of A549 human cancer cells in vitro. The results of the soft
      agar assay indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol
      13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose
      dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or
      TPA-induced transactivation of AP-1 and NF-kappaB over the same dose range. At
      low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2
      terminal kinases, p38 kinase, and MAPK kinase 4 induced by UVB/12-O
      tetradecanoylphorbol-13-acetate, yet higher doses were required to inhibit
      extracellular signal-regulated kinases. Chlorogenic acid also increased the
      enzymatic activities of glutathione S-transferases (GST) and NAD(P)H: quinone
      oxidoreductase. Further studies indicated that chlorogenic acid could stimulate
      the nuclear translocation of Nrf2 (NF-E2-related factor) as well as subsequent
      induction of GSTA1 antioxidant response element (ARE)-mediated GST activity. The
      phosphatidylinositol 3-kinase pathway might be involved in the activation of Nrf2
      translocation. These results provide the first evidence that chlorogenic acid
      could protect against environmental carcinogen-induced carcinogenesis and suggest
      that the chemopreventive effects of chlorogenic acid may be through its up
      regulation of cellular antioxidant enzymes and suppression of ROS-mediated NF
      kappaB, AP-1, and MAPK activation.

PMID- 15944152
TI  - Biosynthesis of vitamin B2: diastereomeric reaction intermediates of archaeal and
      non-archaeal riboflavin synthases.
AB  - The dismutation of 6,7-dimethyl-8-ribityllumazine catalyzed by riboflavin
      synthase affords riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)
      pyrimidinedione. A pentacyclic adduct of two 6,7-dimethyl-8-ribityllumazines has
      been identified earlier as a catalytically competent reaction intermediate of the
      Escherichia coli enzyme. Acid quenching of reaction mixtures of riboflavin
      synthase of Methanococcus jannaschii, a paralog of 6,7-dimethyl-8-ribityllumazine
      synthase devoid of similarity with riboflavin synthases of eubacteria and
      eukaryotes, afforded a compound whose optical absorption and NMR spectra resemble
      that of the pentacyclic E. coli riboflavin synthase intermediate, whereas the
      circular dichroism spectra of the two compounds have similar envelopes but
      opposite signs. Each of the compounds could serve as a catalytically competent
      intermediate for the enzyme by which it was produced, but not vice versa. All
      available data indicate that the respective pentacyclic intermediates of the M.
      jannaschii and E. coli enzymes are diastereomers.

PMID- 15944154
TI  - Coactivator-associated arginine methyltransferase 1, CARM1, affects pre-mRNA
      splicing in an isoform-specific manner.
AB  - Molecular diversity through alternative splicing is important for cellular
      function and development. However, little is known about the factors that
      regulate alternative splicing. Here we demonstrate that one isoform of
      coactivator-associated arginine methyltransferase 1 (named CARM1-v3) associates
      with the U1 small nuclear RNP-specific protein U1C and affects 5' splice site
      selection of the pre-mRNA splicing. CARM1-v3 was generated by the retention of
      introns 15 and 16 of the primary transcript of CARM1. Its deduced protein lacks
      the C-terminal domain of the major isoform of CARM1 and instead has v3-specific
      sequences at the C terminus. CARM1-v3, but not the other isoforms, strongly
      stimulates a shift to the distal 5' splice site of the pre-mRNA when the
      adenoviral E1A minigene is used as a reporter and enhances the exon skips in the
      CD44 reporter. A CARM1-v3 mutant lacking the v3-specific sequences completely
      lost the ability to regulate the alternative splicing patterns. In addition,
      CARM1-v3 shows tissue-specific expression patterns distinct from those of the
      other isoforms. These results suggest that the transcriptional coactivator can
      affect the splice site decision in an isoform-specific manner.

PMID- 15944155
TI  - Regulation of the expression of caspase-9 by the transcription factor activator
      protein-4 in glucocorticoid-induced apoptosis.
AB  - Caspase-9 (Casp-9) induces death signals by triggering other types of caspase
      activation, and its expression greatly influences the onset of apoptosis. During
      the isolation of apoptosis-related genes involved in glucocorticoid (GC)-induced
      cell death in murine thymic lymphomas, we found that the antisense gene of the
      transcription factor activator protein-4 (AP-4) inhibited dexamethasone-induced
      apoptosis. Western blot analysis revealed that the expression of Bcl-xL, Bax, and
      Apaf-1 was not affected in cells transfected with sense or antisense AP-4 genes.
      In contrast, both the expression and activation of Casp-9 were inhibited in the
      antisense AP-4 transfectants. We isolated the 2.4-kb 5'-flanking region of Casp
      9, and the promoter activity was investigated. We found the AP-4-binding sites at
      -1.55 and -1.38 kb to be responsible for the promoter activity. Furthermore, a
      negative cis-element was expected to exist between bases -1140 and -944. When the
      cells were treated with dexamethasone, a rapid down-regulation of AP-4 and Casp-9
      was observed whether the cells were GC-sensitive lymphomas or GC-insensitive L929
      fibroblast cells. In addition, L929 cells pretreated with dexamethasone were
      found to be resistant to subsequent treatment with etoposide, an apoptosis
      inducing reagent. GC has a two-sided effect on apoptosis, i.e. a pro-apoptotic
      effect on certain cell types and a prosurvival effect on other cell types. Our
      findings will explain, at least in part, this effect.

PMID- 15944153
TI  - Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C
      isoforms and secondary messengers in astrocytes.
AB  - Acute mu and kappa opioids activate the ERK/MAPK phosphorylation cascade that
      represents an integral part of the signaling pathway of growth factors in
      astrocytes. By this cross-talk, opioids may impact neural development and
      plasticity among other basic neurobiological processes in vivo. The mu agonist,
      [D-ala2,mephe4,glyol5]enkephalin (DAMGO), induces a transient stimulation of ERK
      phosphorylation, whereas kappa agonist, U69,593, engenders sustained ERK
      activation. Here we demonstrate that acute U69,593 and DAMGO stimulate ERK
      phosphorylation by utilization of different secondary messengers and protein
      kinase C (PKC) isoforms upstream of the growth factor pathway. Immortalized
      astrocytes transfected with either antisense calmodulin (CaM), a mutant mu opioid
      receptor that binds CaM poorly or a dominant negative mutant of PKCepsilon were
      used as a model system to study mu signaling. Evidence was gained to implicate
      CaM and PKCepsilon in DAMGO stimulation of ERK. DAMGO activation of PKCepsilon
      and/or ERK was insensitive to selective inhibitors of Ca2+ mobilization, but it
      was blocked upon phospholipase C inhibition. These results suggest a novel
      mechanism wherein, upon DAMGO binding, CaM is released from the mu receptor and
      activates phospholipase C. Subsequently, phospholipase C generates
      diacylglycerides that activate PKCepsilon. In contrast, U69,593 appears to act
      via phosphoinositide 3-kinase, PKCzeta, and Ca2+ mobilization. These signaling
      components were implicated based on studies with specific inhibitors and a
      dominant negative mutant of PKCzeta. Collectively, our findings on acute opioid
      effects suggest that differences in their mechanism of signaling may contribute
      to the distinct outcomes on ERK modulation induced by chronic mu and kappa
      opioids.

PMID- 15944156
TI  - Yeast as a tractable genetic system for functional studies of the insulin
      degrading enzyme.
AB  - We have developed yeast as an expression and genetic system for functional
      studies of the insulin-degrading enzyme (IDE), which cleaves and inactivates
      certain small peptide molecules, including insulin and the neurotoxic A beta
      peptide. We show that heterologously expressed rat IDE is enzymatically active,
      as judged by the ability of IDE-containing yeast extracts to cleave insulin in
      vitro. We also show that IDE can promote the in vivo production of the yeast a
      factor mating pheromone, a function normally attributed to the yeast enzymes
      Axl1p and Ste23p. However, IDE cannot substitute for the function of Axl1p in
      promoting haploid axial budding and repressing haploid invasive growth,
      activities that require an uncharacterized activity of Axl1p. Particulate
      fractions enriched for Axl1p or Ste23p are incapable of cleaving insulin,
      suggesting that the functional conservation of these enzymes may not be
      bidirectionally conserved. We have made practical use of our genetic system to
      confirm that residues composing the extended zinc metalloprotease motif of M16A
      family enzymes are required for the enzymatic activity of IDE, Ste23p, and Axl1p.
      We have determined that IDE and Axl1p both require an intact C terminus for
      optimal activity. We expect that the tractable genetic system that we have
      developed will be useful for investigating the enzymatic and structure/function
      properties of IDE and possibly for the identification of novel IDE alleles having
      altered substrate specificity.

PMID- 15944157
TI  - Heat shock protein 27 is the major differentially phosphorylated protein involved
      in renal epithelial cellular stress response and controls focal adhesion
      organization and apoptosis.
AB  - We used two-dimensional difference gel electrophoresis to determine early changes
      in the stress-response pathways that precede focal adhesion disorganization
      linked to the onset of apoptosis of renal epithelial cells. Treatment of LLC-PK1
      cells with the model nephrotoxicant 1,2-(dichlorovinyl)-L-cysteine (DCVC)
      resulted in a >1.5-fold up- and down-regulation of 14 and 9 proteins,
      respectively, preceding the onset of apoptosis. Proteins included those involved
      in metabolism, i.e. aconitase and pyruvate dehydrogenase, and those related to
      stress responses and cytoskeletal reorganization, i.e. cofilin, Hsp27, and alpha
      b-crystallin. The most prominent changes were found for Hsp27, which was related
      to a pI shift in association with an altered phosphorylation status of serine
      residue 82. Although both p38 and JNK were activated by DCVC, only inhibition of
      p38 with SB203580 reduced Hsp27 phosphorylation, which was associated with
      accelerated reorganization of focal adhesions, cell detachment, and apoptosis. In
      contrast, inhibition of JNK with SP600125 maintained cell adhesion as well as
      protection against apoptosis. Active JNK co-localized at focal adhesions after
      DCVC treatment in a FAK-dependent manner. Inhibition of active JNK localization
      at focal adhesions did not prevent DCVC-induced phosphorylation of Hsp27.
      Overexpression of a phosphorylation-defective mutant Hsp27 acted as a dominant
      negative and accelerated the DCVC-induced changes in the focal adhesions as well
      as the onset of apoptosis. Our data fit a model whereby early p38 activation
      results in a rapid phosphorylation of Hsp27, a requirement for proper maintenance
      of cell adhesion, thus suppressing renal epithelial cell apoptosis.

PMID- 15944159
TI  - "Natively unfolded" VPg is essential for Sesbania mosaic virus serine protease
      activity.
AB  - Polyprotein processing is a major strategy used by many plant and animal viruses
      to maximize the number of protein products obtainable from a single open reading
      frame. In Sesbania mosaic virus, open reading frame-2 codes for a polyprotein
      that is cleaved into different functional proteins in cis by the N-terminal
      serine protease domain. The soluble protease domain lacking 70-amino-acid
      residues from the N terminus (deltaN70Pro, where Pro is protease) was not active
      in trans. Interestingly, the protease domain exhibited trans-catalytic activity
      when VPg (viral protein genome-linked) was present at the C terminus.
      Bioinformatic analysis of VPg primary structure suggested that it could be a
      disordered protein. Biophysical studies validated this observation, and VPg
      resembled "natively unfolded" proteins. CD spectral analysis showed that the
      deltaN70Pro-VPg fusion protein had a characteristic secondary structure with a
      230 nm positive CD peak. Mutation of Trp-43 in the VPg domain to phenylalanine
      abrogated the positive peak with concomitant loss in cis- and trans-proteolytic
      activity of the deltaN70Pro domain. Further, deletion of VPg domain from the
      polyprotein completely abolished proteolytic processing. The results suggested a
      novel mechanism of activation of the protease, wherein the interaction between
      the natively unfolded VPg and the protease domains via aromatic amino acid
      residues alters the conformation of the individual domains and the active site of
      the protease. Thus, VPg is an activator of protease in Sesbania mosaic virus, and
      probably by this mechanism, the polyprotein processing could be regulated in
      planta.

PMID- 15944158
TI  - Extracellular trafficking of myocilin in human trabecular meshwork cells.
AB  - Myocilin (MYOC) is a protein with a broad expression pattern, but unknown
      function. MYOC associates with intracellular structures that are consistent with
      secretory vesicles, however, in most cell types studied, MYOC is limited to the
      intracellular compartment. In the trabecular meshwork, MYOC associates with
      intracellular vesicles, but is also found in the extracellular space. The purpose
      of the present study was to better understand the mechanism of extracellular
      transport of MYOC in trabecular meshwork cells. Using a biochemical approach, we
      found that MYOC localizes intracellularly to both the cytosolic and particulate
      fractions. When intracellular membranes were separated over a linear sucrose
      gradient, MYOC equilibrated in a fraction less dense than traditional secretory
      vesicles and lysosomes. In pulse-labeling experiments that followed nascent MYOC
      over time, the characteristic doublet observed for MYOC by SDS-PAGE did not
      change, even in the presence of brefeldin A; indicating that MYOC is not
      glycosylated and is not released via a traditional secretory mechanism. When
      conditioned media from human trabecular meshwork cells were examined, both native
      and recombinant MYOC associated with an extracellular membrane population having
      biochemical characteristics of exosomes, and containing the major
      histocompatibility complex class II antigen, HLA-DR. The association of MYOC with
      exosome-like membranes appeared to be specific, on the extracellular face, and
      reversible. Taken together, data suggest that MYOC appears in the extracellular
      space of trabecular meshwork cells by an unconventional mechanism, likely
      associated with exosome-like vesicles.

PMID- 15944160
TI  - The redox state of the baculovirus single-stranded DNA-binding protein LEF-3
      regulates its DNA binding, unwinding, and annealing activities.
AB  - The single-stranded (ss) DNA-binding protein LEF-3 of Autographa californica
      multinucleocapsid nucleopolyhedrovirus promoted Mg(2+)-independent unwinding of
      DNA duplexes and annealing of complementary DNA strands. The unwinding and
      annealing activities of LEF-3 appeared to act in a competitive manner and were
      determined by the ratio of protein to DNA. At subsaturating and saturating
      concentrations, LEF-3 promoted annealing, whereas it promoted unwinding at
      oversaturation of DNA substrates. The LEF-3 binding to ssDNA and unwinding
      activity were sensitive to redox agents and were inhibited by oxidation of thiol
      groups in LEF-3 with 1,1'-azobis(N,N-dimethylformamide) (diamide) or by
      modification with the thiol-conjugating agent N-ethylmaleimide. Both oxidation
      and alkylation increased the dissociation constant of the interaction with model
      oligonucleotides indicating a decrease in an intrinsic affinity of LEF-3 for
      ssDNA. These results proved that free thiol groups are essential both for LEF-3
      interaction with ssDNA and for DNA unwinding. In contrast, oxidation or
      modification of thiol groups stimulated the annealing activity of LEF-3 partially
      due to suppression of its unwinding activity. Treatment of LEF-3 with the
      reducing agent dithiothreitol inhibited annealing, indicating association of this
      activity with the oxidized protein. Thus, the balance between annealing and
      unwinding activities of LEF-3 was determined by the redox state of protein with
      the oxidized state favoring annealing and the reduced state favoring unwinding.
      An LEF-3 mutant in which the conservative cysteine Cys(214) was replaced with
      serine showed both a decreased binding to DNA and a reduced unwinding activity,
      thus indicating that this residue might participate in the regulation of LEF-3
      activities.

PMID- 15944161
TI  - Acute reduction of an origin recognition complex (ORC) subunit in human cells
      reveals a requirement of ORC for Cdk2 activation.
AB  - The origin recognition complex (ORC) is involved in formation of prereplicative
      complexes (pre-RCs) on replication origins in the G1 phase. At the G1/S
      transition, elevated cyclin E-CDK2 activity triggers 1DNA replication to enter S
      phase. The CDK cycle works as an engine that drives progression of cell cycle
      events by successive activation of different types of cyclin-CDK. However, how
      the CDK cycle is coordinated with replication initiation remains elusive. Here we
      report that acute depletion of ORC2 by RNA interference (RNAi) arrests cells with
      low cyclin E-CDK2 activity. This result suggests that loss of a replication
      initiation protein prevents progression of the CDK cycle in G1. p27 and p21
      proteins accumulate following ORC2 RNAi and are required for the CDK2 inhibition.
      Restoration of CDK activity by co-depletion of p27 and p21 allows many ORC2
      depleted cells to enter S phase and go on to mitosis. However, in some cells the
      release of the CDK2 block caused catastrophic events like apoptosis. Therefore,
      the CDK2 inhibition observed following ORC2 RNAi seems to protect cells from
      premature S phase entry and crisis in DNA replication. These results demonstrate
      an unexpected role of ORC2 in CDK2 activation, a linkage that could be important
      for maintaining genomic stability.

PMID- 15944162
TI  - Interaction of the Ty3 reverse transcriptase thumb subdomain with template
      primer.
AB  - Amino acid sequence alignment was used to identify the putative thumb subdomain
      of reverse transcriptase (RT) from the Saccharomyces cerevisiae long terminal
      repeat-containing retrotransposon Ty3. The counterpart to helix alphaH of human
      immunodeficiency virus type 1 (HIV-1) RT, which mediates important interactions
      with a duplex nucleic acid approximately 3-6 bp behind the DNA polymerase
      catalytic center, was identified between amino acids 290 and 298 of the Ty3
      enzyme. The consequences of substituting Ty3 RT Gln290, Phe292, Gly294, Asn297,
      and Tyr298 (the counterparts of HIV-1 RT Gln258, Leu260, Gly262, Asn265, and
      Trp266, respectively) for both DNA polymerase and RNase H activities were
      examined. DNA-dependent DNA synthesis was evaluated on unmodified substrates and
      on duplexes containing targeted insertion of locked nucleic acid analogs and
      abasic lesions in either the template or primer. Based on this combined strategy,
      our data suggest an interaction of Ty3 RT Tyr298 with primer nucleotide -3,
      Gly294 with primer nucleotide -4, and Asn297 with template nucleotide -6.
      Substitution of Ala for Gln290 was well tolerated, despite the high degree of
      conservation at this position. Mutations in the thumb subdomain of Ty3 also
      affected RNase H activity, suggesting a closer spatial relationship between its N
      and C-terminal catalytic centers compared with HIV-1 RT.

PMID- 15944163
TI  - Inhibition of membrane type-1 matrix metalloproteinase by cancer drugs interferes
      with the homing of diabetogenic T cells into the pancreas.
AB  - We have discovered that clinically tested inhibitors of matrix metalloproteinases
      can control the functional activity of T cell membrane type-1 matrix
      metalloproteinase (MT1-MMP) and the onset of disease in a rodent model of type 1
      diabetes in non-obese diabetic mice. We determined that MT1-MMP proteolysis of
      the T cell surface CD44 adhesion receptor affects the homing of T cells into the
      pancreas. We also determined that both the induction of the intrinsic T cell MT1
      MMP activity and the shedding of cellular CD44 follow the adhesion of insulin
      specific, CD8-positive, Kd-restricted T cells to the matrix. Conversely,
      inhibition of these events by AG3340 (a potent hydroxamate inhibitor that was
      widely used in clinical trials in cancer patents) impedes the transmigration of
      diabetogenic T cells into the pancreas and protects non-obese diabetic mice from
      diabetes onset. Overall, our studies have divulged a previously unknown function
      of MT1-MMP and identified a promising novel drug target in type I diabetes.

PMID- 15944164
TI  - Comparison of pancreatic cancer mortality in five countries: France, Italy,
      Japan, UK and USA from WHO mortality database (1960-2000).

PMID- 15944165
TI  - Prevention of osteoporosis: a randomized clinical trial to increase calcium
      intake in children with juvenile rheumatoid arthritis.
AB  - OBJECTIVE: To test the efficacy of a behavioral intervention (BI) compared to an
      enhanced standard of care (ESC) dietary counseling on increasing dietary calcium
      (Ca) intake in children with juvenile rheumatoid arthritis (JRA). METHODS: Three
      day food diaries collected at baseline and posttreatment were analyzed for Ca
      intake in 49 children with JRA randomly assigned to either BI or an ESC
      treatment. RESULTS: Children in the BI (N = 25) demonstrated a significantly
      greater increase in average dietary Ca intake (M = 839) than children in the ESC
      (N = 24; M = 420) (F = 14.39; p < .001). Post hoc analysis revealed that children
      in both groups demonstrated significant gains in dietary Ca intake baseline to
      posttreatment. A significantly greater percentage of children in the BI (92%)
      attained the goal of 1500 mg/Ca at posttreatment compared to the ESC (17%), X2=
      28.09; p < .001. CONCLUSIONS: Behavioral intervention can have a positive impact
      on increasing dietary Ca intake. Future research will need to evaluate the
      maintenance of gains in dietary Ca intake following treatment cessation and the
      impact of increased Ca intake on bone mineral density.

PMID- 15944166
TI  - A comparison of distraction strategies for venipuncture distress in children.
AB  - OBJECTIVE: To compare the effects of two pediatric venipuncture distress
      management distraction strategies that differed in the degree to which they
      required children's interaction. METHODS: Eighty-eight 1- to 7-year-old children
      receiving venipuncture were randomly assigned to one of three treatment
      conditions: interactive toy distraction, passive movie distraction, or standard
      care. Distress was examined via parent, nurse, self-report (children over 4
      years), and observational coding. Engagement in distraction was assessed via
      observational coding. RESULTS: Children in the passive condition were more
      distracted and less distressed than children in the interactive condition.
      Although children in the interactive condition were more distracted than standard
      care children, there were no differences in distress between these groups.
      CONCLUSIONS: Despite literature that suggests that interactive distraction should
      lower distress more than passive distraction, results indicate that a passive
      strategy might be most effective for children's venipuncture. It is possible that
      children's distress interfered with their ability to interact with the
      distractor.

PMID- 15944167
TI  - A randomized controlled trial of a cognitive-behavioral family intervention for
      pediatric recurrent abdominal pain.
AB  - OBJECTIVE: To investigate whether the combination of standard medical care (SMC)
      and short-term cognitive-behavioral family treatment (CBT) in the treatment of
      recurrent abdominal pain (RAP) was more effective than SMC alone. METHODS:
      Children recently diagnosed with RAP via physician examination were randomized
      into SMC (n = 29) and SMC plus CBT (n = 40) groups. Outcome measures included
      multiple dimensions of child and parent reported child pain, somatization, and
      functional disability, and school absences and physician contacts. RESULTS:
      Children and parents participating in the combined SMC + CBT intervention
      reported significantly less child and parent reported child abdominal pain than
      children in the SMC intervention immediately following the intervention and up to
      1 year following study entry, as well as significantly fewer school absences.
      Significant differences in functional disability and somatization were not
      revealed. CONCLUSIONS: These results, in combination with previous studies, add
      support to the effectiveness of CBT intervention in reducing the sensory aspects
      of RAP. Results are discussed with respect to the cost-benefit of integrated
      medical and short-term psychological services.

PMID- 15944168
TI  - Commentary: randomized controlled trials of psychological interventions with
      pediatric populations: the time has come and the Journal of Pediatric Psychology
      is ready.

PMID- 15944169
TI  - Child injury deaths: comparing prevention information from two coding systems.
AB  - OBJECTIVES: The International Classification of Disease (ICD) external cause of
      injury E-codes do not sufficiently identify injury circumstances amenable to
      prevention. The researchers developed an alternative classification system (B
      codes) that incorporates behavioral and environmental factors, for use in
      childhood injury research, and compare the two coding systems in this paper.
      METHODS: All fatal injuries among children less than age five that occurred
      between January 1, 1992, and December 31, 1994, were classified using both B
      codes and E-codes. RESULTS: E-codes identified the most common causes of injury
      death: homicide (24%), fires (21%), motor vehicle incidents (21%), drowning
      (10%), and suffocation (9%). The B-codes further revealed that homicides (51%)
      resulted from the child being shaken or struck by another person; many fires
      deaths (42%) resulted from children playing with matches or lighters; drownings
      (46%) usually occurred in natural bodies of water; and most suffocation deaths
      (68%) occurred in unsafe sleeping arrangements. CONCLUSIONS: B-codes identify
      additional information with specific relevance for prevention of childhood
      injuries.

PMID- 15944170
TI  - Predictors of children's and adolescents' risk perception.
AB  - OBJECTIVE: To test cognitive-developmental, social-cognitive, motivational, and
      cognitive hypotheses about the psychological mechanisms underlying children's
      risk perception. METHOD: Youth (N = 1315) ranging from 9 to 17 years of age
      completed measures assessing adolescent egocentrism, personal experience with
      four negative health events, how much they worried about the health events, and
      their perceived skill for event-related activities. The measures were completed
      twice, 12 months apart. RESULTS: Lacking personal experience with and worrying
      less about health threats were significant predictors of more optimistically
      biased risk perception a year later. CONCLUSIONS: The lack of experience with and
      not worrying about serious health consequences may desensitize children to
      potential health risks. Clinical applications for health education programs are
      discussed.

PMID- 15944171
TI  - Putting the pieces together: preliminary efficacy of a web-based family
      intervention for children with traumatic brain injury.
AB  - OBJECTIVE: To report preliminary efficacy data from a Web-based family problem
      solving intervention to improve parent and child adaptation. METHOD: Eight
      parents and six children with moderate to severe traumatic brain injury (TBI) who
      were injured more than 15 months earlier (M = 16 months) participated in the
      intervention. Families were given computers, Web cameras, and high-speed Internet
      access. Weekly videoconferences with the therapist were conducted after they
      completed self-guided Web exercises on problem-solving, communication, and
      antecedent behavior management strategies. RESULTS: Paired t tests comparing pre-
      and post-intervention scores revealed significant improvements in injury-related
      burden, parental psychiatric symptoms, depression, and parenting stress. There
      were also significant reductions in antisocial behaviors in the injured child,
      but not in self-reported depressive symptoms. CONCLUSIONS: These findings suggest
      that a computer-based intervention may successfully be used to improve both
      parent and child outcomes following TBI in children.

PMID- 15944172
TI  - Informant discrepancy in perceptions of sickle cell disease severity.
AB  - OBJECTIVES: To evaluate whether informants (children, caregivers, and physicians)
      differ in their perceptions of chronic disease severity and the extent to which
      these differences can be explained by objective indices of disease severity, and
      adjustment of the caregiver. METHODS: Participants were 58 children and
      adolescents between the ages of 8 and 18 years diagnosed with sickle cell
      disease. Information on perceptions of disease severity, caregiver adjustment,
      and biological markers of disease severity was obtained at a routine clinic
      follow-up appointment. RESULTS: Analyses indicated significant differences in
      perceptions of disease severity. Psychological adjustment of the caregiver and
      biological indices of disease severity were significant predictors of these
      differences. CONCLUSION: Implications for the association between chronic disease
      and adjustment are discussed.

PMID- 15944173
TI  - Commentary: conducting randomized controlled trials of psychological treatment to
      improve the outcomes of recurrent abdominal pain: contributions and challenges.

PMID- 15944174
TI  - Mitochondrial behaviour in the early stages of ROS stress leading to cell death
      in Arabidopsis thaliana.
AB  - BACKGROUND AND AIMS: Reactive oxygen species (ROS) are involved in triggering
      cell death. To visualize mitochondrial behaviour under ROS stress, transgenic
      arabidopsis plants possessing mitochondrial-targeted GFP (S65T) were studied.
      METHODS: Arabidopsis leaves were treated with ROS and ROS-inducing chemicals such
      as hydrogen peroxide, paraquat and menadione. Microscopic observations were
      carried out using a confocal laser scanning microscope system, and electrolyte
      leakage was also monitored. KEY RESULTS: After treatment, mitochondria showed
      morphological changes from a bacillus-like to a round shape. The size of
      mitochondria treated with H(2)O(2) decreased by half compared with controls.
      Concurrently, cytoplasmic streaming was blocked and mitochondria eventually
      swelled. Treatment of leaves with butanedione monoxime, an inhibitor of myosin
      ATPase, resulted in similar behaviour of mitochondria to that under ROS stress.
      CONCLUSIONS: The results indicate that morphological changes of mitochondria and
      cessation of cytoplasmic streaming may interact, and this phenomenon is one of
      the features of ROS stress-induced cell death.

PMID- 15944175
TI  - Sapling structure and regeneration strategy in 18 Shorea species co-occurring in
      a tropical rainforest.
AB  - BACKGROUND AND AIMS: Inevitable trade-offs in structure may be a basis for
      differentiation in plant strategies. Juvenile trees in different functional
      groups are characterized by specific suites of structural traits such as crown
      architecture and biomass distribution. The relationship between juvenile tree
      structure and function was tested to find out if it is robust among functionally
      and taxonomically similar species of the genus Shorea that coexist sympatrically
      in a tropical rain forest in Borneo. METHODS: The sapling structures of 18
      species were compared for standardized dry masses of 5 and 30 g. Pairwise simple
      correlation and multiple correlation patterns among structural traits of
      juveniles (0.1-1.5 m in height) of 18 Shorea species were examined using
      Pearson's correlation and principal component analysis (PCA), respectively. The
      correlation was then tested between the PCA results and three indices of shade
      tolerance: the net photosynthetic rate, the wood density of mature trees and seed
      size. KEY RESULTS: The structural variation in saplings of the genus Shorea was
      as large as that found in sets of species with much more diverse origins. The PCA
      showed that both crown architecture and allocation to leaves are major sources of
      variation in the structures of the 18 species investigated. Of these two axes,
      allocation to leaves was significantly correlated with wood density and showed a
      limited correlation with photosynthetic rate, whereas crown architecture was
      significantly correlated to seed size. CONCLUSIONS: Overall, the results suggest
      that an allocation trade-off between leaves and other organs, which co-varied
      with wood density and to a certain extent with photosynthetic capacity, accounts
      for the difference in shade tolerance among congeneric, functionally similar
      species. In contrast, the relationship between the architecture and regeneration
      strategy differed from the pattern found between functional groups, and the
      function of crown architecture was ambiguous.

PMID- 15944176
TI  - Putting the plants back into plant ecology: six pragmatic models for
      understanding and conserving plant diversity.
AB  - BACKGROUND: There is a compelling need to protect natural plant communities and
      restore them in degraded landscapes. Activities must be guided by sound
      scientific principles, practical conservation tools, and clear priorities. With
      perhaps one-third of the world's flora facing extinction, scientists and
      conservation managers will need to work rapidly and collaboratively, recognizing
      each other's strengths and limitations. As a guide to assist managers in
      maintaining plant diversity, six pragmatic models are introduced that are already
      available. Although theoretical models continue to receive far more space and
      headlines in scientific journals, more managers need to understand that
      pragmatic, rather than theoretical, models have the most promise for yielding
      results that can be applied immediately to plant communities. SIX PRAGMATIC
      MODELS: For each model, key citations and an array of examples are provided, with
      particular emphasis on wetlands, since "wet and wild" was my assigned theme for
      the Botanical Society of America in 2003. My own work may seem rather prominent,
      but the application and refinement of these models has been a theme for me and my
      many students over decades. The following models are reviewed: (1) species-area:
      larger areas usually contain more species; (2) species-biomass: plant diversity
      is maximized at intermediate levels of biomass; (3) centrifugal organization:
      multiple intersecting environmental gradients maintain regional landscape
      biodiversity; (4) species-frequency: a few species are frequent while most are
      infrequent; (5) competitive hierarchies: in the absence of constraints, large
      canopy-forming species dominate patches of landscape, reducing biological
      diversity; and (6) intermediate disturbance: perturbations such as water level
      fluctuations, fire and grazing are essential for maintaining plant diversity.
      CONCLUSIONS: The good news is that managers faced with protecting or restoring
      landscapes already have this arsenal of tools at their disposal. The bad news is
      that far too few of these models are appreciated.

PMID- 15944177
TI  - Phylogenetic analysis of Petunia sensu Jussieu (Solanaceae) using chloroplast DNA
      RFLP.
AB  - BACKGROUND AND AIMS: The phylogenetic relationships of Petunia sensu Jussieu
      (Petunia sensu Wijsman plus Calibrachoa) are unclear. This study aimed to resolve
      this uncertainty using molecular evidence. METHODS: Phylogenetic trees of 52 taxa
      of Petunia sensu Jussieu were constructed using restriction fragment length
      polymorphism (RFLP) of chloroplast DNA digested with 19 restriction enzymes and
      hybridized with 12 cloned Nicotiana chloroplast DNA fragments as probes. KEY
      RESULTS: In all, 89 phylogenetically informative RFLPs were detected and one 50 %
      majority consensus tree was obtained, using the maximum parsimony method, and one
      distance matrix tree, using the neighbour joining method. Petunia sensu Wijsman
      and Calibrachoa were monophyletic sister clades in both trees. Calibrachoa
      parviflora and C. pygmaea, previously thought to differ from the other species in
      terms of their cross-compatibility, seed morphology, and nuclear DNA content,
      formed a basal clade that was sister to the remainder of Calibrachoa. Several
      clades found in the phylogenetic trees corresponded to their distribution ranges,
      suggesting that recent speciation in the genus Petunia sensu Jussieu occurred
      independently in several different regions. CONCLUSIONS: The separation of
      Petunia sensu Wijsman and Calibrachoa was supported by chloroplast DNA analysis.
      Two groups in the Calibrachoa were also recognized with a high degree of
      confidence.

PMID- 15944178
TI  - International code for phytolith nomenclature 1.0.
AB  - BACKGROUND: Phytoliths (microscopic opal silica particles produced in and between
      the cells of many plants) are a very resilient, often-preserved type of
      microfossil and today, phytolith analysis is widely used in palaeoenvironmental
      studies, botany, geology and archaeology. To date there has been little
      standardization in the way phytoliths are described and classified. SCOPE: This
      paper presents the first International Code for Phytolith Nomenclature (ICPN),
      proposing an easy to follow, internationally accepted protocol to describe and
      name phytoliths.

PMID- 15944179
TI  - The safety of antiepileptic drug withdrawal in patients with non-epileptic
      seizures.
AB  - BACKGROUND: To determine whether withdrawal of anticonvulsant drugs (AED) can be
      carried out safely in patients with non-epileptic seizures (NES). METHODS:
      Prospective evaluation of safety and outcome in 78 patients with NES who
      satisfied a standardised set of criteria for excluding the diagnosis of
      coexisting or underlying epilepsy. FINDINGS: The patients were taking from one to
      three AED. Sixty four patients were withdrawn as outpatients, 14 as inpatients.
      Five patients stopped their drugs abruptly, and two had AED restarted and had to
      be withdrawn again. Otherwise all patients adhered to withdrawal schedules. A new
      type of attack in addition to NES was seen in three patients (complex partial
      seizures in all three cases). NES frequency declined in the group as a whole over
      the period of the study (follow up 6-12 months) in all individuals except for
      eight patients in whom there was a transient increase. Fourteen patients reported
      new physical symptoms after withdrawal; however, no serious adverse events were
      reported. CONCLUSIONS: With appropriate diagnostic investigation and surveillance
      during follow up withdrawal of AED can be achieved safely in patients with NES.

PMID- 15944180
TI  - Levels of CSF prostaglandin E2, cognitive decline, and survival in Alzheimer's
      disease.
AB  - BACKGROUND: Although epidemiological, clinical, and experimental evidence
      indicates that the inducible isoform of cyclo-oxygenase (COX-2) may be involved
      in the pathogenesis of several neurodegenerative disorders, the mechanisms
      whereby COX-2 contributes to Alzheimer's disease are largely unknown. OBJECTIVE:
      To undertake a longitudinal study of CSF levels of a major product of COX
      activity, prostaglandin E2 (PGE2), in relation to cognitive decline and survival
      in patients with Alzheimer's disease. METHODS: CSF PGE2 was measured on at least
      three annual visits in 35 controls and 33 Alzheimer patients (26 necropsy
      confirmed) who completed the Cambridge cognitive assessment (CAMCOG). RESULTS:
      Compared with controls, CSF PGE2 was higher in patients with mild memory
      impairment, but lower in those with more advanced Alzheimer's disease. The median
      survival time of patients with higher initial PGE2 levels was five years longer
      than those with lower levels. CONCLUSIONS: COX activity in Alzheimer's disease
      varies with stage of the disease. PGE2 levels correlate positively with patient
      survival. These findings suggest that inhibition of COX activity does not
      represent a major target for the pharmacological treatment of Alzheimer's
      disease.

PMID- 15944181
TI  - VEGF is crucial for the hepatic vascular development required for lipoprotein
      uptake.
AB  - Hepatic lipid catabolism begins with the transport of lipoprotein remnants from
      the sinusoidal vasculature into hepatocytes by endocytosis via microvilli. To
      test the hypothesis that fenestrated sinusoidal endothelial cells (SECs) are
      crucial for this process, we selectively disrupted SECs by downregulating
      vascular endothelial growth factor (VEGF) signaling, using hepatocyte-specific,
      tetracycline-regulatable expression of a VEGF receptor that can sequester VEGF
      but cannot relay its signal. Newborn mutant livers appeared grossly normal, but
      displayed a dark-red color that was distinguishable from normal physiological
      lipid-rich pink livers. Mutant sinusoidal networks were reduced and their SECs
      lacked fenestrae. Hepatocellular lipid levels were profoundly reduced, as
      determined by Oil Red O staining and transmission electron microscopy, and fewer
      hepatocytic microvilli were evident, indicating impaired lipoprotein endocytosis.
      Levels of apolipoprotein (APO) E bound to mutant sinusoidal networks were
      significantly reduced, and fluorescently-labeled murine remnant lipoproteins
      injected into the blood stream failed to accumulate in the space of Disse and
      diffuse into hepatocytes, providing evidence that reduced hepatocellular lipid
      levels in mutant livers are due to impaired lipoprotein uptake. Temporal
      downregulation of VEGF signaling revealed that it is crucial at all developmental
      stages of hepatic vascular morphogenesis, and repression of the dominant-negative
      effect can rescue the phenotype. These findings provide the first genetic
      evidence that VEGF dynamically regulates SEC fenestration during liver
      organogenesis, a process that is required for lipoprotein uptake by the liver.

PMID- 15944182
TI  - Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic
      organizer.
AB  - The mesencephalic and metencephalic region (MMR) of the vertebrate central
      nervous system develops in response to signals produced by the isthmic organizer
      (IsO). We have previously reported that the LIM homeobox transcription factor
      Lmx1b is expressed within the chick IsO, where it is sufficient to maintain
      expression of the secreted factor wnt1. In this paper, we show that zebrafish
      express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and
      demonstrate that these genes are necessary for key aspects of MMR development.
      Simultaneous knockdown of Lmx1b.1 and Lmx1b.2 using morpholino antisense oligos
      results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO,
      leading ultimately to programmed cell death and the loss of the isthmic
      constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or
      Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and
      lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as
      well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early
      MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as
      throughout much of the embryo. We propose that Lmx1b.1- and Lmx1b.2-mediated
      regulation of wnt1, wnt3a, wnt10b, pax8 and fgf8 maintains cell survival in the
      isthmocerebellar region.

PMID- 15944183
TI  - Control of body size by SMA-5, a homolog of MAP kinase BMK1/ERK5, in C. elegans.
AB  - We have analyzed the sma-5(n678) mutant in C. elegans to elucidate mechanisms
      controlling body size. The sma-5 mutant is very small, grows slowly and its
      intestinal granules look abnormal. We found a 15 kb deletion in the mutant that
      includes a 226 bp deletion of the 3' end of the W06B3.2-coding sequence. Based on
      this result, rescue experiments, RNAi experiments and a newly isolated deletion
      mutant of W06B3.2, we conclude that W06B3.2 is the sma-5 gene. The sma-5 mutant
      has much smaller intestine, body wall muscles and hypodermis than those of the
      wild type. However, the number of intestinal cells or body wall muscle cells is
      not changed, indicating that the sma-5 mutant has much smaller cells. In relation
      to the smaller cell size, the amount of total protein is drastically decreased;
      however, the DNA content of the intestinal nuclei is unchanged in the sma-5
      mutant. The sma-5 gene is expressed in intestine, excretory cell and hypodermis,
      and encodes homologs of a mammalian MAP kinase BMK1/ERK5/MAPK7, which was
      reported to control cell cycle and cell proliferation. Expression of the sma-5
      gene in hypodermis is important for body size control, and it can function both
      organ-autonomously and non-autonomously. We propose that the sma-5 gene functions
      in a MAP kinase pathway to regulate body size mainly through control of cell
      growth.

PMID- 15944184
TI  - PTEN deletion in Bergmann glia leads to premature differentiation and affects
      laminar organization.
AB  - Development of the central nervous system is controlled by both intrinsic and
      extrinsic signals that guide neuronal migration to form laminae. Although defects
      in neuronal mobility have been well documented as a mechanism for abnormal
      laminar formation, the role of radial glia, which provide the environmental cues,
      in modulating neuronal migration is less clear. We provide evidence that loss of
      PTEN in Bergmann glia leads to premature differentiation of this crucial cell
      population and subsequently to extensive layering defects. Accordingly, severe
      granule neuron migration defects and abnormal laminar formation are observed.
      These results uncover an unexpected role for PTEN in regulating Bergmann glia
      differentiation, as well as the importance of time-dependent Bergmann glia
      differentiation during cerebellar development.

PMID- 15944185
TI  - Developmental regulation of the Hox genes during axial morphogenesis in the
      mouse.
AB  - The Hox genes confer positional information to the axial and paraxial tissues as
      they emerge gradually from the posterior aspect of the vertebrate embryo. Hox
      genes are sequentially activated in time and space, in a way that reflects their
      organisation into clusters in the genome. Although this co-linearity of
      expression of the Hox genes has been conserved during evolution, it is a
      phenomenon that is still not understood at the molecular level. This review aims
      to bring together recent findings that have advanced our understanding of the
      regulation of the Hox genes during mouse embryonic development. In particular, we
      highlight the integration of these transducers of anteroposterior positional
      information into the genetic network that drives tissue generation and patterning
      during axial elongation.

PMID- 15944186
TI  - Retinal neurons regulate proliferation of postnatal progenitors and Muller glia
      in the rat retina via TGF beta signaling.
AB  - The number of proliferating cells in the rodent retina declines dramatically
      after birth. To determine if extrinsic factors in the retinal micro-environment
      are responsible for this decline in proliferation, we established cultures of
      retinal progenitors or Muller glia, and added dissociated retinal neurons from
      older retinas. The older cells inhibited proliferation of progenitor cells and
      Muller glia. When these experiments were performed in the presence of
      TGF(beta)RII-Fc fusion protein, an inhibitor of TGF(beta) signaling,
      proliferation was restored. This suggests a retina-derived TGF(beta) signal is
      responsible for the developmental decline in retinal proliferation. TGFbeta
      receptors I and II are expressed in the retina and are located in nestin-positive
      progenitors early in development and glast-positive Muller glia later in
      development. RT-PCR and immunofluorescence data show TGF(beta)2 is the most
      highly expressed TGF(beta)ligand in the postnatal retina, and it is expressed by
      inner retinal neurons. Addition of either TGF(beta)1 or TGF(beta)2 to postnatal
      day 4 retinas significantly inhibited progenitor proliferation, while treatment
      of explanted postnatal day 6 retinas with TGF(beta) signaling inhibitors resulted
      in increased proliferation. Last, we tested the effects of TGF(beta) in vivo by
      injections of TGF(beta) signaling inhibitors: when TGF(beta) signaling is
      inhibited at postnatal day 5.5, proliferation is increased in the central retina;
      and when co-injected with EGF at postnatal day 10, TGF(beta)inhibitors stimulate
      Muller glial proliferation. In sum, these results show that retinal neurons
      produce a cytostatic TGF(beta) signal that maintains mitotic quiescence in the
      postnatal rat retina.

PMID- 15944187
TI  - Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing
      Wnt and Notch signaling pathways.
AB  - In the developing vertebrate retina, progenitor cells initially proliferate but
      begin to produce postmitotic neurons when neuronal differentiation occurs.
      However, the mechanism that determines whether retinal progenitor cells continue
      to proliferate or exit from the cell cycle and differentiate is largely unknown.
      Here, we report that histone deacetylase 1 (Hdac1) is required for the switch
      from proliferation to differentiation in the zebrafish retina. We isolated a
      zebrafish mutant, ascending and descending (add), in which retinal cells fail to
      differentiate into neurons and glial cells but instead continue to proliferate.
      The cloning of the add gene revealed that it encodes Hdac1. Furthermore, the
      ratio of the number of differentiating cells to that of proliferating cells
      increases in proportion to Hdac activity, suggesting that Hdac proteins regulate
      a crucial step of retinal neurogenesis in zebrafish. Canonical Wnt signaling
      promotes the proliferation of retinal cells in zebrafish, and Notch signaling
      inhibits neuronal differentiation through the activation of a neurogenic
      inhibitor, Hairy/Enhancer-of-split (Hes). We found that both the Wnt and
      Notch/Hes pathways are activated in the add mutant retina. The cell-cycle
      progression and the upregulation of Hes expression in the add mutant retina can
      be inhibited by the blockade of Wnt and Notch signaling, respectively. These data
      suggest that Hdac1 antagonizes these pathways to promote cell-cycle exit and the
      subsequent neurogenesis in zebrafish retina. Taken together, these data suggest
      that Hdac1 functions as a dual switch that suppresses both cell-cycle progression
      and inhibition of neurogenesis in the zebrafish retina.

PMID- 15944188
TI  - Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre
      Sertoli cells.
AB  - The nuclear receptor transcription factor Dax1 is hypothesized to play a role in
      testicular development, although the mechanism of its action is unknown. Here, we
      present evidence that Dax1 plays an early essential role in fetal testis
      development. We hypothesize that upregulation of Sox9 expression in precursor
      somatic cells, a process required for their differentiation as Sertoli cells,
      depends on the coordinated expression of Dax1, Sry and another gene, Tda1. Our
      conclusion and model are based on the following experimental findings: (1)
      presence of a mutant Dax1 allele (Dax1-) results in complete gonadal sex reversal
      in C57BL/6JEi (B6) XY mice, whereas testes develop in DBA/2J (D2) and (B6xD2)F1
      XY mice; (2) B6-DAX1 sex reversal is inherited as a complex trait that includes
      the chromosome 4 gene Tda1; (3) B6 Dax1-/Y fetal gonads initiate development as
      ovaries, even though Sry expression is activated at the correct time and at
      appropriate levels; (4) upregulation of Sox9 does not occur in B6 Dax1-/Y fetal
      gonads in spite of apparently normal Sry expression; and (5) overexpression of
      Sry in B6 Dax1-/Y fetal gonads upregulates Sox9 and corrects testis development.

PMID- 15944190
TI  - Dynamics of the basement membrane in invasive epithelial clusters in Drosophila.
AB  - The basement membrane (BM) represents a barrier to cell migration, which has to
      be degraded to promote invasion. However, the role and behaviour of the BM during
      the development of pre-invasive cells is only poorly understood. Drosophila
      border cells (BCs) provide an attractive genetic model in which to study the
      cellular mechanisms underlying the migration of mixed cohorts of epithelial
      cells. BCs are made of two different epithelial cell types appearing sequentially
      during oogenesis: the polar cells and the outer BCs. Here, we show that the pre
      invasive polar cells undergo an unusual and asymmetrical apical capping with
      major basement membrane proteins, including the two Drosophila Collagen IV alpha
      chains, Laminin A and Perlecan. Capping of polar cells proceeds through a novel,
      basal-to-apical transcytosis mechanism that involves the small GTPase Drab5.
      Apical capping is transient and is followed by rapid shedding prior to the
      initiation of BC migration, suggesting that the apical cap blocks migration.
      Consistently, non-migratory polar cells remain capped. We further show that
      JAK/STAT signalling and recruitment of outer BCs are required for correct
      shedding and migration. The dynamics of the BM represents a marker of migratory
      BC, revealing a novel developmentally regulated behaviour of BM coupled to
      epithelial cell invasiveness.

PMID- 15944189
TI  - Comparative analysis of genes downstream of the Hoxd cluster in developing digits
      and external genitalia.
AB  - Mammalian Hox genes encode transcription factors that are crucial for proper
      morphogenesis along the various body axes. Despite their extensive structural and
      functional characterization, the nature of their target genes remains elusive. We
      have addressed this question by using DNA microarrays to screen for genes whose
      expression in developing distal forelimbs and genital eminences was significantly
      modified in the absence of the full Hoxd gene complement. This comparative
      approach not only identified specific candidate genes, but also allowed the
      examination of whether a similar Hox expression pattern in distinct tissues leads
      to the modulation of the same or different downstream genes. We report here a set
      of potential target genes, most of which were not previously known to play a role
      in the early stages of either limb or genital bud development. Interestingly, we
      find that the majority of these candidate genes are differentially expressed in
      both structures, although often at different times. This supports the idea that
      both appendices involve similar genetic controls, both upstream and downstream of
      the Hox gene family. These results highlight the surprising mechanistic
      relationship between these rather different body parts and suggest a common
      developmental strategy to build up the most distal appendicular structures of the
      body, i.e. the digits and the penis/clitoris.

PMID- 15944191
TI  - A Pbx1-dependent genetic and transcriptional network regulates spleen ontogeny.
AB  - The genetic control of cell fate specification, morphogenesis and expansion of
      the spleen, a crucial lymphoid organ, is poorly understood. Recent studies of
      mutant mice implicate various transcription factors in spleen development, but
      the hierarchical relationships between these factors have not been explored. In
      this report, we establish a genetic network that regulates spleen ontogeny, by
      analyzing asplenic mice mutant for the transcription factors Pbx1, Hox11 (Tlx1),
      Nkx3.2 (Bapx1) and Pod1 (capsulin, Tcf21). We show that Hox11 and Nkx2.5, among
      the earliest known markers for splenic progenitor cells, are absent in the
      splenic anlage of Pbx1 homozygous mutant (-/-) embryos, implicating the TALE
      homeoprotein Pbx1 in splenic cell specification. Pbx1 and Hox11 genetically
      interact in spleen formation and loss of either is associated with a similar
      reduction of progenitor cell proliferation and failed expansion of the splenic
      anlage. Chromatin immunoprecipitation assays show that Pbx1 binds to the Hox11
      promoter in spleen mesenchymal cells, which co-express Pbx1 and Hox11.
      Furthermore, Hox11 binds its own promoter in vivo and acts synergistically with
      TALE proteins to activate transcription, supporting its role in an auto
      regulatory circuit. These studies establish a Pbx1-Hox11-dependent genetic and
      transcriptional pathway in spleen ontogeny. Additionally, we demonstrate that
      while Nkx3.2 and Pod1 control spleen development via separate pathways, Pbx1
      genetically regulates key players in both pathways, and thus emerges as a central
      hierarchical co-regulator in spleen genesis.

PMID- 15944192
TI  - AP2-dependent signals from the ectoderm regulate craniofacial development in the
      zebrafish embryo.
AB  - AP2 transcription factors regulate many aspects of embryonic development. Studies
      of AP2a (Tfap2a) function in mice and zebrafish have demonstrated a role in
      patterning mesenchymal cells of neural crest origin that form the craniofacial
      skeleton, while the mammalian Tfap2b is required in both the facial skeleton and
      kidney. Here, we show essential functions for zebrafish tfap2a and tfap2b in
      development of the facial ectoderm, and for signals from this epithelium that
      induce skeletogenesis in neural crest cells (NCCs). Zebrafish embryos deficient
      for both tfap2a and tfap2b show defects in epidermal cell survival and lack NCC
      derived cartilages. We show that cartilage defects arise after NCC migration
      during skeletal differentiation, and that they can be rescued by transplantation
      of wild-type ectoderm. We propose a model in which AP2 proteins play two distinct
      roles in cranial NCCs: an early cell-autonomous function in cell specification
      and survival, and a later non-autonomous function regulating ectodermal signals
      that induce skeletogenesis.

PMID- 15944193
TI  - NKX6 transcription factor activity is required for alpha- and beta-cell
      development in the pancreas.
AB  - In diabetic individuals, the imbalance in glucose homeostasis is caused by loss
      or dysfunction of insulin-secreting beta-cells of the pancreatic islets. As
      successful generation of insulin-producing cells in vitro could constitute a cure
      for diabetes, recent studies have explored the molecular program that underlies
      beta-cell formation. From these studies, the homeodomain transcription factor
      NKX6.1 has proven to be a key player. In Nkx6.1 mutants, beta-cell numbers are
      selectively reduced, while other islet cell types develop normally. However, the
      molecular events downstream of NKX6.1, as well as the molecular pathways that
      ensure residual beta-cell formation in the absence of NKX6.1 are largely unknown.
      Here, we show that the Nkx6.1 paralog, Nkx6.2, is expressed during pancreas
      development and partially compensates for NKX6.1 function. Surprisingly, our
      analysis of Nkx6 compound mutant mice revealed a previously unrecognized
      requirement for NKX6 activity in alpha-cell formation. This finding suggests a
      more general role for NKX6 factors in endocrine cell differentiation than
      formerly suggested. Similar to NKX6 factors, the transcription factor MYT1 has
      recently been shown to regulate alpha- as well as beta-cell development. We
      demonstrate that expression of Myt1 depends on overall Nkx6 gene dose, and
      therefore identify Myt1 as a possible downstream target of Nkx6 genes in the
      endocrine differentiation pathway.

PMID- 15944194
TI  - Aflatoxin B1 albumin adduct levels and cellular immune status in Ghanaians.
AB  - Although aflatoxins (AFs) have been shown to be immune-suppressive agents in
      animals, the potential role of AFs in modifying the distribution and function of
      leukocyte subsets in humans has never been assessed. We examined the cellular
      immune status of 64 Ghanaians in relation to levels of aflatoxin B1 (AFB1)
      albumin adducts in plasma. The percentages of leukocyte immunophenotypes in
      peripheral blood, CD4+ T cell proliferative response, CD4+ T(h) and CD8+ T cell
      cytokine profiles and monocyte phagocytic activity were measured using flow
      cytometry. NK cell cytotoxic function was determined by perforin and tumor
      necrosis factor-alpha expression in CD3-CD56+ NK cells. AFB1-albumin adducts
      levels ranged from 0.3325 to 2.2703 (mean = 0.9972 +/- 0.40, median = 0.9068)
      pmol mg(-1) albumin. Study participants with high AFB1 levels had significantly
      lower percentages of CD3+ and CD19+ cells that showed the CD69+ activation marker
      (CD3+CD69+ and CD19+CD69+) than participants with low AFB1 levels (P = 0.002 for
      both). Also, the percentages of CD8+ T cells that contained perforin or both
      perforin and granzyme A were significantly lower in participants with high AFB1
      levels compared with those with low AFB1 (P = 0.012 for both). Low levels of
      CD3+CD69+ (r = -0.32, P = 0.016) and CD19+CD69+ (r = -0.334, P = 0.010) cells
      were significantly associated with high AFB1 levels using correlation analysis.
      By multivariate analysis, there were strong negative correlations between the
      percentages of these cells (CD3+CD69+: b = -0.574, P = 0.001, and CD19+CD69+: b =
      -0.330, P = 0.032) and AFB1 levels. These alterations in immunological parameters
      in participants with high AFB1 levels could result in impairments in cellular
      immunity that could decrease host resistance to infections.

PMID- 15944195
TI  - DC-SIGN, but not sDC-SIGN, can modulate IL-2 production from PMA- and anti-CD3
      stimulated primary human CD4 T cells.
AB  - Dendritic cell (DC)-specific intercellular cell adhesion molecule-3 (ICAM-3)
      grabbing non-integrin (DC-SIGN) is expressed on the surface of DCs and
      specialized macrophages and can support T cell proliferation. Antibody-mediated
      co-ligation of CD3 and ICAM-3, the ligand for both DC-SIGN and leukocyte function
      associated antigen-1, leads to T cell activation. Therefore, we tested to see
      whether DC-SIGN or a splice variant of dendritic cell-specific intercellular cell
      adhesion molecule-3-grabbing non-integrin (sDC-SIGN) can co-stimulate primary
      human T cells. The sDC-SIGN lacking the transmembrane domain encoded by exon 3
      localizes to the cytoplasm of cells and is not secreted. Both B7 and DC-SIGN co
      stimulated phorbol myristate acetate-stimulated CD4+ cells as compared with
      controls. However, unlike B7, both DC-SIGN and sDC-SIGN failed to co-stimulate
      CD4+ T cells treated with sub-optimal amounts of anti-CD3 (2 microg ml(-1)) as
      defined by a lack of CD69 and CD25 up-regulation, cell division and cytokine
      secretion. Instead, DC-SIGN, and not sDC-SIGN, induced a small but consistent
      down-regulation of IL-2 production by these CD4+ T cells. In contrast, DC-SIGN in
      the presence of 30 mug ml(-1) of anti-CD3 modestly up-regulated cytokine
      production as compared with control. These results suggest that DC-SIGN can
      differentially modulate T cell stimulation.

PMID- 15944196
TI  - Role of the FcepsilonRI beta-chain ITAM as a signal regulator for mast cell
      activation with monomeric IgE.
AB  - The beta-chain of the high-affinity receptor for IgE (FcepsilonRI) plays a
      crucial role for amplification of the intracellular signaling in mast cells upon
      FcepsilonRI cross-linking by IgE*antigen complexes (IgE*Ag). Some monomeric IgE
      as well as IgE*Ag stimulate FcepsilonRI-signaling pathways, leading to cell
      activation, whereas the biological functions of the beta-chain in the monomeric
      IgE-mediated mast cell signaling and responses are largely unknown. In the
      present study, FcepsilonRI is reconstituted with either wild-type beta-chain or
      mutated beta-chain immunoreceptor tyrosine-based activation motif (ITAM)
      employing retrovirus-mediated gene transfer into the FcepsilonRI beta-chain-/-
      mast cells. We demonstrated that the transfectants with mutated beta-chain ITAM
      stimulated with monomeric IgE sufficiently produce inflammatory cytokines,
      although degranulation, intracellular Ca(2+) mobilization and leukotriene C(4)
      synthesis are significantly reduced. Furthermore, analyses of molecular
      mechanisms of the signaling revealed that the expression of cytokine genes and
      activation of extracellular signal-regulated kinase 1/2 and protein kinase C were
      significantly delayed in the beta-chain ITAM mutant cells stimulated with
      monomeric IgE, suggesting that the beta-chain ITAM regulates kinetics of gene
      transcriptions and signaling pathways for cytokine production. These findings for
      the first time revealed the unique functions of the beta-chain ITAM in both
      chemical mediator release and cytokine production of mast cells upon monomeric
      IgE stimulation.

PMID- 15944197
TI  - A functional polymorphism within the MRP1 gene locus identified through its
      genomic signature of positive selection.
AB  - Searching for genomic evidence of positive selection has been hailed as an
      attractive strategy for identifying functional polymorphisms. Here, we
      demonstrate the feasibility of identifying functional polymorphism at the MRP1
      gene locus using this strategy. The 190 kDa MRP1 protein is an efflux pump that
      regulates the accumulation of xenobiotics and drugs in cells. Functional sequence
      variations within this gene might account, in part, for inter-individual and
      population differences in drug response. To identify single nucleotide
      polymorphisms (SNPs) within the MRP1 gene with potentially important functional
      significance, we scanned for genomic signatures of recent positive selection at
      this locus in approximately 480 individuals sampled from the Chinese, Malay,
      Indian, European-American and African-American populations. The genetic profile
      of SNPs at this locus revealed high haplotype diversity and weak linkage
      disequilibrium (LD). Despite this weak LD, major allele G of SNP 5'FR/G-260C
      contained within a high frequency haplotype exhibited extended haplotype
      homozygosity across 135 kb in European-Americans. Using two independent genomic
      tests, long-range haplotype (LRH) test and the F(ST) statistic, we found
      statistical evidence of positive selection for this allele in the European
      American population. When this SNP was recapitulated in an in vitro MRP1 promoter
      reporter assay, significantly lower activity was observed from the G-containing
      promoter when compared with the C-containing promoter in all four cell lines that
      we tested (P<0.01). These observations confirm the power of this strategy in
      identifying functionally different alleles of genes and suggest that the
      different alleles at this SNP locus in the MRP1 gene may account, in part, for
      inter-individual variations and population differences in drug response.

PMID- 15944198
TI  - Mitochondrial localization of the Parkinson's disease related protein DJ-1:
      implications for pathogenesis.
AB  - Both homozygous (L166P, M26I, deletion) and heterozygous mutations (D149A, A104T)
      in the DJ-1 gene have been identified in Parkinson's disease (PD) patients. The
      biochemical function and subcellular localization of DJ-1 protein have not been
      clarified. To date the localization of DJ-1 protein has largely been described in
      studies over-expressing tagged DJ-1 protein in vitro. It is not known whether the
      subcellular localization of over-expressed DJ-1 protein is identical to that of
      endogenously expressed DJ-1 protein both in vitro and in vivo. To clarify the
      subcellular localization and function of DJ-1, we generated three highly specific
      antibodies to DJ-1 protein and investigated the subcellular localization of
      endogenous DJ-1 protein in both mouse brain tissues and human neuroblastoma
      cells. We have found that DJ-1 is widely distributed and is highly expressed in
      the brain. By cell fractionation and immunogold electron microscopy, we have
      identified an endogenous pool of DJ-1 in mitochondrial matrix and inter-membrane
      space. To further investigate whether pathogenic mutations might prevent the
      distribution of DJ-1 to mitochondria, we generated human neuroblastoma cells
      stably transfected with wild-type (WT) or mutant (M26I, L166P, A104T, D149A) DJ-1
      and performed mitochondrial fractionation and confocal co-localization imaging
      studies. When compared with WT and other mutants, L166P mutant exhibits largely
      reduced protein level. However, the pathogenic mutations do not alter the
      distribution of DJ-1 to mitochondria. Thus, DJ-1 is an integral mitochondrial
      protein that may have important functions in regulating mitochondrial physiology.
      Our findings of DJ-1's mitochondrial localization may have important implications
      for understanding the pathogenesis of PD.

PMID- 15944199
TI  - Foxl2 is required for commitment to ovary differentiation.
AB  - Genetic control of female sex differentiation from a bipotential gonad in mammals
      is poorly understood. We find that mouse XX gonads lacking the forkhead
      transcription factor Foxl2 form meiotic prophase oocytes, but then activate the
      genetic program for somatic testis determination. Pivotal Foxl2 action thus
      represses the male gene pathway at several stages of female gonadal
      differentiation. This suggests the possible continued involvement of sex
      determining genes in maintaining ovarian function throughout female reproductive
      life.

PMID- 15944200
TI  - Copy number polymorphism and expression level variation of the human alpha
      defensin genes DEFA1 and DEFA3.
AB  - We have defined unexpectedly extensive copy number variation at the human anti
      microbial alpha-defensin genes DEFA1 and DEFA3, encoding human neutrophil
      peptides HNP-1, HNP-2 and HNP-3. There was variation in both number and position
      of DEFA1/DEFA3 genes in arrays of 19 kb tandem repeats on 8p23.1, so that the
      DEFA1 and DEFA3 genes appear to be interchangeable variant cassettes within
      tandem gene arrays. For this reason, the official symbol for this locus has been
      revised to DEFA1A3. The total number of gene copies per diploid genome varied
      between four and 11 in a sample of 111 control individuals from the UK, with
      approximately 10% (11/111) of people lacking DEFA3 completely. DEFA1 appeared to
      be at high copy number in all great apes studied; at one variable site in the
      repeat unit, both variants have persisted in humans, chimpanzees and gorillas
      since their divergence. Analysis of expression levels in human white blood cells
      showed a clear correlation between the relative proportions of DEFA1:DEFA3 mRNA
      and corresponding gene numbers. However, there was no relationship between total
      (DEFA1+DEFA3) mRNA levels and total gene copy number, suggesting the superimposed
      influence of trans-acting factors. The persistence of DEFA1 at high copy number
      in other apes suggests an alternative model for the early stages of the evolution
      of novel genes by duplication and divergence. Duplicated genes present in variant
      tandem arrays may have greater potential than simple duplications for the
      combinatorial creation of new functions by recombination and gene conversion,
      while still preserving pre-existing functions on the same haplotype.

PMID- 15944201
TI  - Diverse small-molecule modulators of SMN expression found by high-throughput
      compound screening: early leads towards a therapeutic for spinal muscular
      atrophy.
AB  - We have exploited the existence of a second copy of the human SMN gene (SMN2) to
      develop a high-throughput screening strategy to identify potential small molecule
      therapeutics for the genetic disease spinal muscular atrophy (SMA), which is
      caused by the loss of the SMN1 gene. Our screening process was designed to
      identify synthetic compounds that increase the total amount of full-length SMN
      messenger RNA and protein arising from the SMN2 gene, thereby suppressing the
      deleterious effects of losing SMN1. A cell-based bioassay was generated that
      detects SMN2 promoter activity, on which greater than 550,000 compounds was
      tested. This resulted in the identification of 17 distinct compounds with
      confirmed biological activity on the cellular primary assay, belonging to nine
      different structural families. Six of the nine scaffolds were chosen on the basis
      of their drug-like features to be tested for their ability to modulate SMN gene
      expression in SMA patient-derived fibroblasts. Five of the six compound classes
      altered SMN mRNA levels or mRNA splicing patterns in SMA patient-derived
      fibroblasts. Two of the compound classes, a quinazoline compound series and an
      indole compound, also increased SMN protein levels and nuclear gem/Cajal body
      numbers in patient-derived cells. In addition, these two distinct scaffolds
      showed additive effects when used in combination, suggesting that they may act on
      different molecular targets. The work described here has provided the foundation
      for a successful medicinal chemistry effort to further advance these compounds as
      potential small molecule therapeutics for SMA.

PMID- 15944202
TI  - Actions of TNF-alpha on glutamatergic synaptic transmission in the central
      nervous system.
AB  - Increasing attention is being paid to the role of inflammatory and immune
      molecules in the modulation of central nervous system (CNS) function. Tumour
      necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine, the receptors
      for which are expressed on neurones and glial cells throughout the CNS. Through
      the action of its two receptors, it has a broad range of actions on neurones
      which may be either neuroprotective or neurotoxic. It plays a facilitatory role
      in glutamate excitotoxicity, both directly and indirectly by inhibiting glial
      glutamate transporters on astrocytes. Additionally, TNF-alpha has direct effects
      on glutamate transmission, for example increasing expression of AMPA receptors on
      synapses. TNF-alpha also plays a role in synaptic plasticity, inhibiting long
      term potentiation (LTP), a process dependent on p38 mitogen activated kinase (p38
      MAP) kinase. In the following review we look at these and other effects of TNF
      alpha in the CNS.

PMID- 15944203
TI  - Enhanced osmotic responsiveness in angiotensin AT1a receptor deficient mice:
      evidence for a role for AT1b receptors.
AB  - Experiments were performed to study the role of angiotensin (Ang) AT1a and AT1b
      receptor subtypes in osmotic regulation of blood pressure using gene deletion and
      pharmacological methods. The cardiovascular effects of hypertonic saline (HS) or
      vasopressin (VP) delivered via vascular catheters were measured in Ang AT1a gene
      deletion (AT1a-/-) and control (AT1a+/+) mice. Blood pressure (BP) and heart rate
      (HR) were recorded in conscious mice using direct carotid catheters. Plasma
      osmolality and VP concentration were also measured. The major finding was that
      deletion of AT1a receptors resulted in enhanced BP response to osmotic
      stimulation. This was seen after acute HS injection (20 microl, 20% NaCl). The
      peak percentage change in mean arterial pressure (MAP) was 15.4+/-1.9% versus
      28.1+/-2.4% (AT1a+/+versus AT1a-/-, respectively). Losartan (AT1 antagonist), but
      not PD123319 (AT2 antagonist), inhibited the HS-induced MAP response,
      specifically in AT1a-/- mice. Plasma osmolality and VP concentration were
      elevated after HS injection with no differences noted between groups. Vascular
      injection of VP (5 ng g-1) increased BP and HR, with similar MAP response between
      groups. Evidence shows that removal of Ang AT1a receptors results in a
      significant enhancement in the pressor response to acute osmotic stimulation.
      Studies of AT1 receptor blockade indicate that complementary Ang AT1b receptors,
      but not AT2 receptors, may be involved in the osmotic response.

PMID- 15944204
TI  - Verification of the exponential model of body temperature decrease after death in
      pigs.
AB  - The authors have conducted a systematic study in pigs to verify the models of
      post-mortem body temperature decrease currently employed in forensic medicine.
      Twenty-four hour automatic temperature recordings were performed in four body
      sites starting 1.25 h after pig killing in an industrial slaughterhouse under
      typical environmental conditions (19.5-22.5 degrees C). The animals had been
      randomly selected under a regular manufacturing process. The temperature decrease
      time plots drawn starting 75 min after death for the eyeball, the orbit soft
      tissues, the rectum and muscle tissue were found to fit the single-exponential
      thermodynamic model originally proposed by H. Rainy in 1868. In view of the
      actual intersubject variability, the addition of a second exponential term to the
      model was demonstrated to be statistically insignificant. Therefore, the two
      exponential model for death time estimation frequently recommended in the
      forensic medicine literature, even if theoretically substantiated for individual
      test cases, provides no advantage as regards the reliability of estimation in an
      actual case. The improvement of the precision of time of death estimation by the
      reconstruction of an individual curve on the basis of two dead body temperature
      measurements taken 1 h apart or taken continuously for a longer time (about 4 h),
      has also been proved incorrect. It was demonstrated that the reported increase of
      precision of time of death estimation due to use of a multiexponential model,
      with individual exponential terms to account for the cooling rate of the specific
      body sites separately, is artifactual. The results of this study support the use
      of the eyeball and/or the orbit soft tissues as temperature measuring sites at
      times shortly after death. A single-exponential model applied to the eyeball
      cooling has been shown to provide a very precise estimation of the time of death
      up to approximately 13 h after death. For the period thereafter, a better
      estimation of the time of death is obtained from temperature data collected from
      the muscles or the rectum.

PMID- 15944205
TI  - Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport
      of neuroactive tryptophan metabolites.
AB  - Tryptophan metabolites such as kynurenate (KYNA), xanthurenate (XA), and
      quinolinate are considered to have an important impact on many physiological
      processes, especially brain function. Many of these metabolites are secreted with
      the urine. Because organic anion transporters (OATs) facilitate the renal
      secretion of weak organic acids, we investigated whether the secretion of
      bioactive tryptophan metabolites is mediated by OAT1 and OAT3, two prominent
      members of the OAT family. Immunohistochemical analyses of the mouse kidneys
      revealed the expression of OAT1 to be restricted to the proximal convoluted
      tubule (representing S1 and S2 segments), whereas OAT3 was detected in almost all
      parts of the nephron, including macula densa cells. In the mouse brain, OAT1 was
      found to be expressed in neurons of the cortex cerebri and hippocampus as well as
      in the ependymal cell layer of the choroid plexus. Six tryptophan metabolites,
      including the bioactive substances KYNA, XA, and the serotonin metabolite 5
      hydroxyindol acetate inhibited [(3)H]p-aminohippurate (PAH) or 6
      carboxyfluorescein (6-CF) uptake by 50-85%, demonstrating that these compounds
      interact with OAT1 as well as with OAT3. Half-maximal inhibition of mOAT1
      occurred at 34 muM KYNA and 15 muM XA, and it occurred at 8 muM KYNA and 11.5 muM
      XA for mOAT3. Quinolinate showed a slight but significant inhibition of [(3)H]PAH
      uptake by mOAT1 and no alteration of 6-CF uptake by mOAT3. [(14)C]-Glutarate (GA)
      uptake was examined for both transporters and demonstrated differences in the
      transport rate for this substrate by a factor of 4. Trans-stimulation experiments
      with GA revealed that KYNA and XA are substrates for mOAT1. Our results support
      the idea that OAT1 and OAT3 are involved in the secretion of bioactive tryptophan
      metabolites from the body. Consequently, they are crucial for the regulation of
      central nervous system tryptophan metabolite concentration.

PMID- 15944206
TI  - Cell-specific posttranscriptional regulation of CFTR gene expression via
      influence of MAPK cascades on 3'UTR part of transcripts.
AB  - Expression of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR)
      gene, which contains the mutations responsible for CF, is regulated by cytokines
      (TNF-alpha and IL-1beta) in a cell-specific manner. TNF-alpha decreases CFTR mRNA
      in human colon cell lines (HT-29), but not in pulmonary cell lines (Calu-3), and
      IL-1beta increases it only in Calu-3 cells. We looked for the cytokine-induced
      posttranscriptional regulation of CFTR gene expression and studied the modulation
      of CFTR mRNA stability linked to its 3' untranslated sequence (3'UTR) in HT-29
      and Calu-3 cells. The stability of CFTR mRNA was analyzed by Northern blot after
      in vitro incubation of total RNAs from CFTR-expressing cells with cytosolic
      proteins extracted from control or cytokine-treated HT-29 and Calu-3 cells. CFTR
      mRNA was degraded only by extracts of TNF-alpha-treated HT-29 cells and not by
      cytosolic proteins from untreated or IL-1beta-treated HT-29 cells. In contrast,
      extracts of untreated Calu-3 cells enhanced CFTR mRNA degradation, and IL-1beta
      treatment inhibited this; TNF-alpha had no significant effect. The 3'UTR part of
      CFTR mRNA was found to be required for this posttranscriptional regulation. The
      5' part of the 3'UTR (the 217 first bases), which contains two AUUUA sequences,
      was implicated in CFTR mRNA destabilization and the following 136 bases,
      containing several C-repeats in U-rich environment, in its protection. The
      proteins, which reacted with the U- and C-repeats of CFTR mRNA 3'UTR, were mainly
      controlled by stimulation of the p42/p44 and p38 MAP kinase cascades with
      interaction between these pathways. This posttranscriptional control of gene
      expression is a common feature of CFTR and many proteins of inflammation.

PMID- 15944207
TI  - Opposite effects of Ni2+ on Xenopus and rat ENaCs expressed in Xenopus oocytes.
AB  - The epithelial Na+ channel (ENaC) is modulated by various extracellular factors,
      including Na+, organic or inorganic cations, and serine proteases. To identify
      the effect of the divalent Ni2+ cation on ENaCs, we compared the Na+ permeability
      and amiloride kinetics of Xenopus ENaCs (xENaCs) and rat ENaCs (rENaCs)
      heterologously expressed in Xenopus oocytes. We found that the channel cloned
      from the kidney of the clawed toad Xenopus laevis [wild-type (WT) xENaC] was
      stimulated by external Ni2+, whereas the divalent cation inhibited the channel
      cloned from the rat colon (WT rENaC). The kinetics of amiloride binding were
      determined using noise analysis of blocker-induced fluctuation in current adapted
      for the transoocyte voltage-clamp method, and Na+ conductance was assessed using
      the dual electrode voltage-clamp (TEVC) technique. The inhibitory effect of Ni2+
      on amiloride binding is not species dependent, because Ni2+ decreased the
      affinity (mainly reducing the association rate constant) of the blocker in both
      species in competition with Na+. Importantly, using the TEVC method, we found a
      prominent difference in channel conductance at hyperpolarizing voltage pulses. In
      WT xENaCs, the initial ohmic current response was stimulated by Ni2+, whereas the
      secondary voltage-activated current component remained unaffected. In WT rENaCs,
      only a voltage-dependent block by Ni2+ was obtained. To further study the origin
      of the xENaC stimulation by Ni2+, and based on the rationale of the well-known
      high affinity of Ni2+ for histidine residues, we designed alpha-subunit mutants
      of xENaCs by substituting histidines that were expressed in oocytes, together
      with WT beta- and gamma-subunits. Changing His215 to Asp in one putative
      amiloride-binding domain (WYRFHY) in the extracellular loop between Na+ channel
      membrane segments M1 and M2 had no influence on the stimulatory effect of Ni2+,
      and neither did complete deletion of this segment. Next, we mutated His416
      flanked by His411 and Cys417, a unique site for possible heavy metal ion
      chelation, and, with this quality, most proximal (approximately 100 amino acids
      upstream of the second putative amiloride binding site at the pore entrance), was
      found localized at M2. Replacing His416 with arginine, aspartate, tyrosine, and
      alanine clearly affected amiloride binding in all cases, as well as Na+
      conductance, as expressed in the xENaC current-voltage relationship, especially
      with regard to aspartate and tyrosine. However, similarly to those obtained with
      the WYRFHY stretch, none of these mutations could either abolish the stimulating
      effect of Ni2+ or reverse it to an inhibitory type.

PMID- 15944208
TI  - Functional characterization of high-affinity Na(+)/dicarboxylate cotransporter
      found in Xenopus laevis kidney and heart.
AB  - The SLC13 gene family includes sodium-coupled transporters for citric acid cycle
      intermediates and sulfate. The present study describes the sequence and
      functional characterization of a SLC13 family member from Xenopus laevis, the
      high-affinity Na(+)/dicarboxylate cotransporter xNaDC-3. The cDNA sequence of
      xNaDC-3 codes for a protein of 602 amino acids that is approximately 70%
      identical to the sequences of mammalian NaDC-3 orthologs. The message for xNaDC-3
      is found in the kidney, liver, intestine, and heart. The xNaDC-3 has a high
      affinity for substrate, including a K(m) for succinate of 4 muM, and it is
      inhibited by the NaDC-3 test substrates 2,3-dimethylsuccinate and adipate. The
      transport of succinate by xNaDC-3 is dependent on sodium, with sigmoidal
      activation kinetics, and lithium can partially substitute for sodium. As with
      other members of the family, xNaDC-3 is electrogenic and exhibits inward
      substrate-dependent currents in the presence of sodium. However, other
      electrophysiological properties of xNaDC-3 are unique and involve large leak
      currents, possibly mediated by anions, that are activated by binding of sodium or
      lithium to a single site.

PMID- 15944209
TI  - PAK1 induces podosome formation in A7r5 vascular smooth muscle cells in a PAK
      interacting exchange factor-dependent manner.
AB  - Remodeling of the vascular smooth muscle cytoskeleton is essential for cell
      motility involved in the development of diseases such as arteriosclerosis and
      restenosis. The p21-activated kinase (PAK), which is an effector of the Rho
      GTPases Rac and Cdc42, has been shown to be involved in cytoskeletal remodeling
      and cell motility. We show herein that expression of cytoskeletally active
      constructs of PAK1 is able to induce the formation of dynamic, podosome-like F
      actin columns in the A7r5 vascular smooth muscle cell line. Most of these actin
      columns appear at the junctions between stress fibers and focal adhesions and
      contain several known podosomal protein markers, such as cortactin, Arp2/3, alpha
      actinin, and vinculin. The kinase activity of PAK plays a role in the regulation
      of the turnover rates of these actin columns but is not essential for their
      formation. The ability of PAK to interact with the PAK-interacting exchange
      factor (PIX) but not with Rac or Cdc42, however, is required for the formation of
      the actin columns as well as for the translocation of PIX and G protein-coupled
      receptor kinase-interacting protein (GIT) to focal adhesions adjacent to the
      actin columns. These findings suggest that interaction between PAK and PIX, as
      well as the recruitment of PIX and GIT to focal adhesions, plays an important
      role in the formation of actin columns that resemble podosomes induced by phorbol
      ester in vascular smooth muscle cells.

PMID- 15944210
TI  - Adhesion-dependent activation of CaMKII and regulation of ERK activation in
      vascular smooth muscle.
AB  - Cell adhesion-dependent activation of ERK1/2 has been linked functionally to
      focal adhesion dynamics. We previously reported that in adherent vascular smooth
      muscle (VSM) cells, CaMKII mediates ERK1/2 activation in response to Ca(2+)
      mobilizing stimuli. In the present study, we tested whether CaMKII regulates
      ERK1/2 signaling in response to VSM cell adhesion. Using an antibody that
      specifically recognizes CaMKII autophosphorylated on Thr(287), we determined that
      CaMKII is rapidly activated (within 1 min) after the adherence of cells on
      multiple ECM substrates. Activation of CaMKII on fibronectin was unaffected in
      cells overexpressing focal adhesion kinase (FAK)-related nonkinase (FRNK), an
      endogenous inhibitor of FAK. Furthermore, CaMKII was rapidly and robustly
      activated in VSM cells plated on poly-l-lysine. These results suggest that
      adhesion-dependent CaMKII activation is integrin independent. Adhesion-dependent
      FAK activation on fibronectin was not affected in cells treated with the
      selective CaMKII inhibitor KN-93 (30 muM) or in cells in which the expression of
      CaMKII with small interfering RNA (siRNA) was suppressed, although tyrosine
      phosphorylation of paxillin was inhibited in CaMKII-delta(2)-suppressed cells.
      Sustained ERK1/2 activation that was dependent on FAK activation (inhibited by
      FRNK) was also attenuated by CaMKII inhibition or siRNA-mediated gene silencing.
      Rapid ERK1/2 activation that preceded FAK and paxillin activation was detected
      upon VSM cell adhesion to poly-l-lysine, and this response was inhibited by
      CaMKII gene silencing. These results indicate that integrin-independent CaMKII
      activation is an early signal during VSM cell adhesion that positively modulates
      ERK1/2 signaling through FAK-dependent and FAK-independent mechanisms.

PMID- 15944211
TI  - Prodefensins are matrix proteins of specific granules in human neutrophils.
AB  - Defensins are potent antimicrobial and proinflammatory peptides. The human
      neutrophil defensins human neutrophil peptide (HNP)-1-3 are synthesized as 94
      amino acide (aa) preproHNPs, which are converted to 75 aa proHNPs by
      cotranslational removal of a 19 aa endoplasmic reticulum signal peptide. At the
      promyelocytic stage of myelopoiesis, proHNPs are further proteolytically modified
      and accumulate in azurophil granules as 29-30 aa HNPs. In contrast, proHNPs
      produced by more mature myeloid cells are not subjected to proteolytic cleavage
      and undergo a high degree of constitutive exocytosis. The proHNPs are devoid of
      antimicrobial potential, and the significance of their secretion is unknown. To
      investigate whether mature neutrophils contain proHNPs, we developed antibodies
      against proHNP-1 by DNA immunization of rabbits. In addition, antibodies against
      the 45 aa proHNP pro-piece were raised by conventional immunization procedures.
      These antibodies allowed detection of proHNPs in homogenates of peripheral blood
      neutrophils. The proHNPs were isolated by affinity chromatography, and their
      identity was confirmed by mass spectrometry and N-terminal aa sequence analysis.
      Finally, the neutrophil proHNPs were identified as novel matrix proteins of
      specific granules by subcellular fractionation experiments, release studies, and
      immunoelectron microscopy. Thus, human neutrophils not only store large amounts
      of mature defensins in azurophil granules but also contain a more easily
      mobilized reservoir of unprocessed prodefensins in specific granules.

PMID- 15944212
TI  - Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced
      neutrophil recruitment in vivo.
AB  - Angiotensin-II (Ang-II) has inflammatory activity and is involved in different
      diseases associated with the cardiovascular system. This study has evaluated the
      effect of boldine (B), and two phenanthrene alkaloids semisynthesized by us,
      secoboldine (SB) and boldine methine (BM), on Ang-II-induced neutrophil
      recruitment. Intraperitoneal administration of 1 nM Ang-II induced significant
      neutrophil accumulation, which was maximal at 4-8 h. BM inhibited neutrophil
      infiltration into the peritoneal cavity at 4 h and 8 h by 73% and 77%,
      respectively, SB at 8 h by 55%, and B had no effect on this response. Although BM
      inhibited the release of cytokine-inducible neutrophil
      chemoattractant/keratinocyte-derived chemokine, macrophage inflammatory protein-2
      (MIP-2), and platelet-activating factor (PAF) elicited by Ang-II, SB only reduced
      the release of MIP-2 after 4 h of its administration. Sixty-minute superfusion of
      the rat mesentery with 1 nM Ang-II induced a significant increase in the
      leukocyte-endothelial cell interactions and P-selectin up-regulation, which were
      inhibited by 1 microM BM and SB. The generation of reactive oxygen species (ROS)
      in endothelial cells stimulated with Ang-II was inhibited significantly by the
      three alkaloids tested. BM also diminished Ang-II-induced interleukin-8 release
      from endothelial cells and blocked the PAF receptor on human neutrophils
      (concentration of the compound needed to produce 50% inhibition value: 28.2
      microM). Therefore, BM is a potent inhibitor of Ang-II-induced neutrophil
      accumulation in vivo. This effect appears to be mediated through inhibition of
      CXC chemokine and PAF release, ROS scavenging activity, and blockade of the PAF
      receptor. Thus, it may have potential therapeutic interest for the control of
      neutrophil recruitment that occurs in inflammation associated with elevated
      levels of Ang-II.

PMID- 15944213
TI  - The impact of glucuronidation on the bioactivation and DNA adduction of the
      cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in vivo.
AB  - UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of many
      different chemicals. Glucuronidation is especially important for detoxifying
      reactive intermediates from metabolic reactions, which otherwise can be
      biotransformed into highly reactive cytotoxic or carcinogenic species.
      Detoxification of certain food-borne-carcinogenic heterocyclic amines (HAs) is
      highly dependent on UGT1A-mediated glucuronidation. 2-Amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP), the most mass abundant carcinogenic HA found
      in well-done cooked meat, is extensively glucuronidated by UGT1A proteins. In
      humans, CYP1A2 catalyzed N-hydroxylation and subsequent UGT1A-mediated
      glucuronidation is a dominant pathway in the metabolism of PhIP. Therefore,
      changes in glucuronidation rates could significantly alter PhIP metabolism. To
      determine the importance of UGT1A-mediated glucuronidation in the
      biotransformation of PhIP, hepatic UGT1A deficient Gunn and UGT1A proficient
      Wistar rats were exposed to a 100 microg/kg oral dose of [(14)C]PhIP. Urine was
      collected over 24 h and the PhIP urinary metabolite profiles were compared
      between the two strains. After the 24 h exposure, livers and colons were removed
      and analyzed for DNA adduct formation by accelerator mass spectrometry. Wistar
      rats produced several PhIP and N-hydroxy-PhIP glucuronides that accounted for
      approximately 25% of the total amount of recovered urinary metabolites. In the
      Gunn rats, PhIP and N-hydroxy-PhIP glucuronides were reduced by 68-92%, compared
      with the Wistar rats. PhIP-DNA adduct analysis from the Gunn rats revealed a
      correlation between reduced urinary PhIP and N-hydroxy-PhIP glucuronide levels
      and increased hepatic DNA adducts, compared with the Wistar rats. In the colon,
      DNA adduct levels were lower in the Gunn rats compared with the Wistar rats,
      suggesting deficient hepatic UGT1A activity provides protection against DNA
      adduct formation in peripheral tissue. Due to differences in PhIP metabolism
      between humans and rodents, extrapolation of these results to the human situation
      must be done with caution. These results indicate that UGT1A-mediated
      glucuronidation of PhIP and N-hydroxy-PhIP is an important pathway for PhIP
      detoxification, and demonstrate the importance of tissue-specific metabolism.
      Tissues with reduced UGT1A activity can have a higher rate of PhIP activation and
      be more inclined to form DNA adducts compared with tissues with normal UGT1A
      activity.

PMID- 15944214
TI  - Life-span inhalation exposure to mainstream cigarette smoke induces lung cancer
      in B6C3F1 mice through genetic and epigenetic pathways.
AB  - Although cigarette smoke has been epidemiologically associated with lung cancer
      in humans for many years, animal models of cigarette smoke-induced lung cancer
      have been lacking. This study demonstrated that life time whole body exposures of
      female B6C3F1 mice to mainstream cigarette smoke at 250 mg total particulate
      matter/m(3) for 6 h per day, 5 days a week induces marked increases in the
      incidence of focal alveolar hyperplasias, pulmonary adenomas, papillomas and
      adenocarcinomas. Cigarette smoke-exposed mice (n = 330) had a 10-fold increase in
      the incidence of hyperplastic lesions, and a 4.6-fold (adenomas and papillomas),
      7.25-fold (adenocarcinomas) and 5-fold (metastatic pulmonary adenocarcinomas)
      increase in primary lung neoplasms compared with sham-exposed mice (n = 326).
      Activating point mutations in codon 12 of the K-ras gene were identified at a
      similar rate in tumors from sham-exposed mice (47%) and cigarette smoke-exposed
      mice (60%). The percentages of transversion and transition mutations were similar
      in both the groups. Hypermethylation of the death associated protein (DAP)-kinase
      and retinoic acid receptor (RAR)-beta gene promoters was detected in tumors from
      both sham- and cigarette smoke-exposed mice, with a tendency towards increased
      frequency of RAR-beta methylation in the tumors from the cigarette smoke-exposed
      mice. These results emphasize the importance of the activation of K-ras and
      silencing of DAP-kinase and RAR-beta in lung cancer development, and confirm the
      relevance of this mouse model for studying lung tumorigenesis.

PMID- 15944215
TI  - Inhibitory effect of meloxicam, a cyclooxygenase-2 inhibitor, on N-nitrosobis (2
      oxopropyl) amine induced biliary carcinogenesis in Syrian hamsters.
AB  - Pancreaticobiliary maljunction (PBM) is a high risk factor in biliary tract
      carcinoma. The chemopreventive action of a cyclooxygenase (COX)-2 inhibitor
      (meloxicam) on N-nitrosobis (2-oxopropyl) amine (BOP)-induced gallbladder cancer
      in hamster PBM models was investigated. In 7-week-old female Syrian golden
      hamsters, the extrahepatic bile duct at the distal end of the common duct was
      ligated and cholecystoduodenostomy was performed (group I). In group II, the same
      surgery was performed and from week 4 after surgery, 10 mg/kg of BOP was injected
      subcutaneously once a week with a 1-week interval. In group III, in addition to
      the measures employed in group II, 5 mg/kg/day of meloxicam was administered once
      a day, every weekday. Pathological findings in the gallbladder in week 20 after
      surgery were as follows. In group I, proper epithelium (PE) was predominant and
      there was no cancer. In group II, PE was predominant, but there was also
      hyperplasia and atypical epithelium (AE) recognized in 8 of 11 cases (72.7%); the
      area of AE was more extensive than that in group I. Carcinoma in situ (CIS) was
      recognized in 4 of 11 cases (36.4%) in group II. Group III showed the same
      pathological findings as group I. However, compared with group II, the incidence
      of AE decreased to 27.3% and no cancerous lesion was observed. In week 20 after
      surgery, the proliferative cell nuclear antigen labeling index in group III was
      statistically significantly lower than in group II (P = 0.045). No statistically
      significant differences were noted among the groups in terms of apoptosis
      labeling index in week 20 after surgery. In conclusion, it was confirmed that
      meloxicam suppresses carcinogenesis in hamster PBM models and its mechanism may
      be based on the suppression of cell growth.

PMID- 15944216
TI  - Health care-related economic burden of the polycystic ovary syndrome during the
      reproductive life span.
AB  - CONTEXT: The polycystic ovary syndrome (PCOS) is the most common endocrine
      abnormality of reproductive-aged women today, affecting approximately 6.6% of
      unselected reproductive-aged women (approximately 4 million women in the United
      States) (1990 National Institutes of Health criteria), and potentially represents
      a significant financial burden to our health care. OBJECTIVE: The objective of
      the study was to define, using current definitions and prevalence or incidence
      data, the minimal economic burden that PCOS in reproductive-aged women represents
      for the United States. DESIGN: The study design was a literature review. SETTING:
      The study was conducted at a tertiary care center. PATIENTS OR OTHER
      PARTICIPANTS: There were no patients or other participants. INTERVENTION(S): We
      performed a systematic review of the published medical literature to identify
      studies evaluating epidemiology of reproductive-age PCOS and its clinical
      consequences and costs. We tied general societal cost data for the different
      health consequences to reproductive-age PCOS costs, using prevalence data. MAIN
      OUTCOME MEASURE(S): The main measure in the study was total health care-related
      economic costs. RESULTS: We estimated the mean annual cost of the initial
      evaluation to be dollar 93 million (2.1% of total costs), that of hormonally
      treating menstrual dysfunction/abnormal uterine bleeding to be dollar 1.35
      billion (31.0% of total), that of providing infertility care to be dollar 533
      million (12.2% of total), that of PCOS-associated diabetes to be dollar 1.77
      billion (40.5% of total), and that of treating hirsutism to be dollar 622 million
      (14.2% of total). CONCLUSIONS: The total cost of evaluating and providing care to
      reproductive-aged PCOS women in the United States is dollar 4.36 billion. Because
      the cost of the diagnostic evaluation accounted for a relatively minor part of
      the total costs (approximately 2%), more widespread and liberal screening for the
      disorder appears be a cost-effective strategy, leading to earlier diagnosis and
      intervention and possibly the amelioration and prevention of serious sequelae.

PMID- 15944217
TI  - Leptin secretion by human ejaculated spermatozoa.
AB  - INTRODUCTION: Leptin action is a dynamic area of investigation that continues to
      broaden beyond the basic lipostatic model originally envisaged. Here, we show
      that leptin is expressed in and secreted from human ejaculated spermatozoa.
      METHODS: By RT-PCR, Western blot, and immunofluorescence techniques, we have
      demonstrated that human sperm express leptin. RIA method evidenced leptin
      secretion. Phosphatidyl-inositol-kinase-3 (PI3K)/Akt pathway was examined by PI3K
      activity assay and Western blot. Leptin and insulin regulation of glycogen
      synthesis was evaluated by glycogen synthase activity (GSA). RESULTS: The large
      differences of leptin secretion between uncapacitated and capacitated sperm
      suggest a functional role for leptin in capacitation. Indeed, in uncapacitated
      sperm, leptin enhances both cholesterol efflux and protein tyrosine
      phosphorylation. In uncapacitated sperm, both insulin and leptin increased PI3K
      activity, Akt S473, and glycogen synthase kinase-3 S9 phosphorylation.
      Interestingly, during capacitation, concomitantly to the massive release of both
      hormones, we observed a strong reduction in the phosphorylation of glycogen
      synthase kinase-3 S9, kinase downstream of Akt that regulates the glycogen
      synthase. Our results from GSA showed that the enzymatic activity was
      significantly higher in uncapacitated than in capacitated sperm. Particularly, in
      uncapacitated sperm, GSA appeared to depend on the hormones concentration,
      because the enzymatic activity was stimulated at low doses, whereas it was
      inhibited at high doses. Moreover, both leptin and insulin regulate in autocrine
      fashion sperm glycogen synthesis. CONCLUSION: Leptin secretion by sperm suggests
      that the male gamete may be able to modulate its metabolism independently by
      systemic leptin. These data open new considerations about leptin significance in
      male fertility.

PMID- 15944218
TI  - Mutant kinesin-2 motor subunits increase chromosome loss.
AB  - The Chlamydomonas anterograde intraflagellar transport motor, kinesin-2, is
      isolated as a heterotrimeric complex containing two motor subunits and a nonmotor
      subunit known as kinesin-associated polypeptide or KAP. One of the two motor
      subunits is encoded by the FLA10 gene. The sequence of the second motor subunit
      was obtained by mass spectrometry and sequencing. It shows 46.9% identity with
      the Fla10 motor subunit and the gene maps to linkage group XII/XIII near RPL9.
      The temperature-sensitive flagellar assembly mutants fla1 and fla8 are linked to
      this kinesin-2 motor subunit. In each strain, a unique single point mutation
      gives rise to a unique single amino acid substitution within the motor domain.
      The fla8 strain is named fla8-1 and the fla1 strain is named fla8-2. The fla8 and
      fla10 alleles show a chromosome loss phenotype. To analyze this chromosome loss
      phenotype, intragenic revertants of fla8-1, fla8-2, and fla10-14 were generated.
      The analysis of the mutants and the revertants demonstrates the importance of a
      pocket in the amino terminus of these motor subunits for both motor activity and
      for a novel, dominant effect on the fidelity of chromosome segregation.

PMID- 15944219
TI  - Differential in vivo binding dynamics of somatic and oocyte-specific linker
      histones in oocytes and during ES cell nuclear transfer.
AB  - The embryonic genome is formed by fusion of a maternal and a paternal genome. To
      accommodate the resulting diploid genome in the fertilized oocyte dramatic global
      genome reorganizations must occur. The higher order structure of chromatin in
      vivo is critically dependent on architectural chromatin proteins, with the family
      of linker histone proteins among the most critical structural determinants.
      Although somatic cells contain numerous linker histone variants, only one, H1FOO,
      is present in mouse oocytes. Upon fertilization H1FOO rapidly populates the
      introduced paternal genome and replaces sperm-specific histone-like proteins. The
      same dynamic replacement occurs upon introduction of a nucleus during somatic
      cell nuclear transfer. To understand the molecular basis of this dynamic histone
      replacement process, we compared the localization and binding dynamics of somatic
      H1 and oocyte-specific H1FOO and identified the molecular determinants of binding
      to either oocyte or somatic chromatin in living cells. We find that although both
      histones associate readily with chromatin in nuclei of somatic cells, only H1FOO
      is capable of correct chromatin association in the germinal vesicle stage oocyte
      nuclei. This specificity is generated by the N-terminal and globular domains of
      H1FOO. Measurement of in vivo binding properties of the H1 variants suggest that
      H1FOO binds chromatin more tightly than somatic linker histones. We provide
      evidence that both the binding properties of linker histones as well as
      additional, active processes contribute to the replacement of somatic histones
      with H1FOO during nuclear transfer. These results provide the first mechanistic
      insights into the crucial step of linker histone replacement as it occurs during
      fertilization and somatic cell nuclear transfer.

PMID- 15944220
TI  - Adhesion-dependent and contractile ring-independent equatorial furrowing during
      cytokinesis in mammalian cells.
AB  - Myosin II-dependent contraction of the contractile ring drives equatorial
      furrowing during cytokinesis in animal cells. Nonetheless, myosin II-null cells
      of the cellular slime mold Dictyostelium divide efficiently when adhering to
      substrates by making use of polar traction forces. Here, we show that in the
      presence of 30 microM blebbistatin, a potent myosin II inhibitor, normal rat
      kidney (NRK) cells adhering to fibronectin-coated surfaces formed equatorial
      furrows and divided in a manner strikingly similar to myosin II-null
      Dictyostelium cells. Such blebbistatin-resistant cytokinesis was absent in
      partially detached NRK cells and was disrupted in adherent cells if the advance
      of their polar lamellipodia was disturbed by neighboring cells. Y-27632 (40
      microM), which inhibits Rho-kinase, was similar to 30 microM blebbistatin in that
      it inhibited cytokinesis of partially detached NRK cells but only prolonged
      furrow ingression in attached cells. In the presence of 100 microM blebbistatin,
      most NRK cells that initiated anaphase formed tight furrows, although scission
      never occurred. Adherent HT1080 fibrosarcoma cells also formed equatorial furrows
      efficiently in the presence of 100 microM blebbistatin. These results provide
      direct evidence for adhesion-dependent, contractile ring-independent equatorial
      furrowing in mammalian cells and demonstrate the importance of substrate adhesion
      for cytokinesis.

PMID- 15944221
TI  - A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for
      ATP secretion.
AB  - ATP is emerging as an ubiquitous extracellular messenger. However, measurement of
      ATP concentrations in the pericellular space is problematic. To this aim, we have
      engineered a firefly luciferase-folate receptor chimeric protein that retains the
      N-terminal leader sequence and the C-terminal GPI anchor of the folate receptor.
      This chimeric protein, named plasma membrane luciferase (pmeLUC), is targeted and
      localized to the outer aspect of the plasma membrane. PmeLUC is sensitive to ATP
      in the low micromolar to millimolar level and is insensitive to all other
      nucleotides. To identify pathways for nonlytic ATP release, we transfected pmeLUC
      into cells expressing the recombinant or native P2X7 receptor (P2X7R). Both cell
      types release large amounts of ATP (100-200 microM) in response to P2X7R
      activation. This novel approach unveils a hitherto unsuspected nonlytic pathway
      for the release of large amounts of ATP that might contribute to spreading
      activation and recruitment of immune cells at inflammatory sites.

PMID- 15944222
TI  - Large-scale profiling of Rab GTPase trafficking networks: the membrome.
AB  - Rab GTPases and SNARE fusion proteins direct cargo trafficking through the
      exocytic and endocytic pathways of eukaryotic cells. We have used steady state
      mRNA expression profiling and computational hierarchical clustering methods to
      generate a global overview of the distribution of Rabs, SNAREs, and coat
      machinery components, as well as their respective adaptors, effectors, and
      regulators in 79 human and 61 mouse nonredundant tissues. We now show that this
      systems biology approach can be used to define building blocks for membrane
      trafficking based on Rab-centric protein activity hubs. These Rab-regulated hubs
      provide a framework for an integrated coding system, the membrome network, which
      regulates the dynamics of the specialized membrane architecture of differentiated
      cells. The distribution of Rab-regulated hubs illustrates a number of facets that
      guides the overall organization of subcellular compartments of cells and tissues
      through the activity of dynamic protein interaction networks. An interactive
      website for exploring datasets comprising components of the Rab-regulated hubs
      that define the membrome of different cell and organ systems in both human and
      mouse is available at http://www.membrome.org/.

PMID- 15944223
TI  - Phosphatidylinositol-4-kinase type II alpha is a component of adaptor protein-3
      derived vesicles.
AB  - A membrane fraction enriched in vesicles containing the adaptor protein (AP) -3
      cargo zinc transporter 3 was generated from PC12 cells and was used to identify
      new components of these organelles by mass spectrometry. Proteins prominently
      represented in the fraction included AP-3 subunits, synaptic vesicle proteins,
      and lysosomal proteins known to be sorted in an AP-3-dependent way or to interact
      genetically with AP-3. A protein enriched in this fraction was
      phosphatidylinositol-4-kinase type IIalpha (PI4KIIalpha). Biochemical,
      pharmacological, and morphological analyses supported the presence of PI4KIIalpha
      in AP-3-positive organelles. Furthermore, the subcellular localization of
      PI4KIIalpha was altered in cells from AP-3-deficient mocha mutant mice. The
      PI4KIIalpha normally present both in perinuclear and peripheral organelles was
      substantially decreased in the peripheral membranes of AP-3-deficient mocha
      fibroblasts. In addition, as is the case for other proteins sorted in an AP-3
      dependent way, PI4KIIalpha content was strongly reduced in nerve terminals of
      mocha hippocampal mossy fibers. The functional relationship between AP-3 and
      PI4KIIalpha was further explored by PI4KIIalpha knockdown experiments. Reduction
      of the cellular content of PI4KIIalpha strongly decreased the punctate
      distribution of AP-3 observed in PC12 cells. These results indicate that
      PI4KIIalpha is present on AP-3 organelles where it regulates AP-3 function.

PMID- 15944224
TI  - Basal body duplication and maintenance require one member of the Tetrahymena
      thermophila centrin gene family.
AB  - Centrins, small calcium binding EF-hand proteins, function in the duplication of
      a variety of microtubule organizing centers. These include centrioles in humans,
      basal bodies in green algae, and spindle pole bodies in yeast. The ciliate
      Tetrahymena thermophila contains at least four centrin genes as determined by
      sequence homology, and these have distinct localization and expression patterns.
      CEN1's role at the basal body was examined more closely. The Cen1 protein
      localizes primarily to two locations: one is the site at the base of the basal
      body where duplication is initiated. The other is the transition zone between the
      basal body and axoneme. CEN1 is an essential gene, the deletion of which results
      in the loss of basal bodies, which is likely due to defects in both basal body
      duplication and basal body maintenance. Analysis of the three other centrins
      indicates that two of them function at microtubule-rich structures unique to
      ciliates, whereas the fourth is not expressed under conditions examined in this
      study, although when artificially expressed it localizes to basal bodies. This
      study provides evidence that in addition to its previously known function in the
      duplication of basal bodies, centrin is also important for the integrity of these
      organelles.

PMID- 15944225
TI  - Asymptotic freedom: from paradox to paradigm.

PMID- 15944226
TI  - IFN-gamma-induced immune adaptation of the proteasome system is an accelerated
      and transient response.
AB  - Peptide generation by the proteasome is rate-limiting in MHC class I-restricted
      antigen presentation in response to IFN-gamma. IFN-gamma-induced de novo
      formation of immunoproteasomes, therefore, essentially supports the rapid
      adjustment of the mammalian immune system. Here, we report that the molecular
      interplay between the proteasome maturation protein (POMP) and the proteasomal
      beta5i subunit low molecular weight protein 7 (LMP7) has a key position in this
      immune adaptive program. IFN-gamma-induced coincident biosynthesis of POMP and
      LMP7 and their direct interaction essentially accelerate immunoproteasome
      biogenesis compared with constitutive 20S proteasome assembly. The dynamics of
      this process is determined by rapid LMP7 activation and the immediate LMP7
      dependent degradation of POMP. Silencing of POMP expression impairs recruitment
      of both beta5 subunits into the proteasome complex, resulting in decreased
      proteasome activity, reduced MHC class I surface expression, and induction of
      apoptosis. Furthermore, our data reveal that immunoproteasomes exhibit a
      considerably shortened half-life, compared with constitutive proteasomes. In
      consequence, our studies demonstrate that the cytokine-induced rapid immune
      adaptation of the proteasome system is a tightly regulated and transient response
      allowing cells to return rapidly to a normal situation once immunoproteasome
      function is no longer required.

PMID- 15944227
TI  - Identification of novel deletion breakpoints bordered by segmental duplications
      in the NF1 locus using high resolution array-CGH.
AB  - BACKGROUND: Segmental duplications flanking the neurofibromatosis type 1 (NF1)
      gene locus on 17q11 mediate most gene deletions in NF1 patients. However, the
      large size of the gene and the complexity of the locus architecture pose
      difficulties in deletion analysis. We report the construction and application of
      the first NF1 locus specific microarray, covering 2.24 Mb of 17q11, using a non
      redundant approach for array design. The average resolution of analysis for the
      array is approximately 12 kb per measurement point with an increased average
      resolution of 6.4 kb for the NF1 gene. METHODS: We performed a comprehensive
      array-CGH analysis of 161 NF1 derived samples and identified heterozygous
      deletions of various sizes in 39 cases. The typical deletion was identified in 26
      cases, whereas 13 samples showed atypical deletion profiles. RESULTS: The size of
      the atypical deletions, contained within the segment covered by the array, ranged
      from 6 kb to 1.6 Mb and their breakpoints could be accurately determined.
      Moreover, 10 atypical deletions were observed to share a common breakpoint either
      on the proximal or distal end of the deletion. The deletions identified by array
      CGH were independently confirmed using multiplex ligation-dependent probe
      amplification. Bioinformatic analysis of the entire locus identified 33 segmental
      duplications. CONCLUSIONS: We show that at least one of these segmental
      duplications, which borders the proximal breakpoint located within the NF1 intron
      1 in five atypical deletions, might represent a novel hot spot for deletions. Our
      array constitutes a novel and reliable tool offering significantly improved
      diagnostics for this common disorder.

PMID- 15944228
TI  - Chronometry of visual responses in frontal eye field, supplementary eye field,
      and anterior cingulate cortex.
AB  - The latency and variability of latency of single-unit responses to identical
      visual stimulation were measured in the frontal eye field (FEF), supplementary
      eye field (SEF), and anterior cingulate cortex (ACC) of macaque monkeys
      performing visually guided saccades. The mean visual response latency was
      significantly shorter in FEF (64 ms) than in SEF (81 ms) or ACC (100 ms), and
      latency values determined by four methods agreed. The latency variability of the
      visual response was respectively less in FEF (21 ms) than in SEF (37 ms) or ACC
      (41 ms). Latency, variability of latency, and magnitude of the visual responses
      were correlated within FEF and SEF but not ACC. These characteristics of the
      visual response are consistent with the degree of convergence of visual afferents
      to these areas and constrain hypotheses about visual processing in the frontal
      lobe.

PMID- 15944229
TI  - Movement quantity and frequency coding in human motor areas.
AB  - Studies of movement coding have indicated a relationship between functional MRI
      signals and increasing frequency of movement in primary motor cortex and other
      motor-related structures. However, prior work has typically used block-designs
      and fixed-time intervals across the varying movements frequencies that may
      prevent ready distinction of brain mechanisms related to movement quantity and,
      especially, movement frequency. Here, we obtained functional MRI signals from
      humans working in an event-related design to extract independent activation
      related to movement quantity or movement frequency. Participants tapped once,
      twice, or thrice at 1, 2, or 3 Hz, and the tapping evoked activation related to
      movement quantity in the precentral and postcentral gyri, supplementary motor
      area, cerebellum, putamen, and thalamus. Increasing movement frequency failed to
      yield activation in these motor-related areas, although linear movement frequency
      affects occurred in nonmotor regions of cortex and subcortex. Our results do not
      replicate prior data suggesting movement frequency encoding in motor-related
      areas; instead we observed movement quantity coding in motor-related brain areas.
      The discrepancy between prior studies and this study likely relates to
      methodology concerns. We suggest that the movement quantity relationships in
      human motor areas and encoding of movement frequency in nonmotor areas may
      reflect a functional anatomical substrate for mediating distinct movement
      parameters.

PMID- 15944230
TI  - Neuromuscular adaptation during skill acquisition on a two degree-of-freedom
      target-acquisition task: isometric torque production.
AB  - In this study we attempted to identify the principles that govern the changes in
      neural control that occur during repeated performance of a multiarticular
      coordination task. Eight participants produced isometric flexion/extension and
      pronation/supination torques at the radiohumeral joint, either in isolation
      (e.g., flexion) or in combination (e.g., flexion-supination), to acquire targets
      presented by a visual display. A cursor superimposed on the display provided
      feedback of the applied torques. During pre- and postpractice tests, the
      participants acquired targets in eight directions located either 3.6 cm (20%
      maximal voluntary contraction [MVC]) or 7.2 cm (40% MVC) from a neutral cursor
      position. On each of five consecutive days of practice the participants acquired
      targets located 5.4 cm (30% MVC) from the neutral position. EMG was recorded from
      eight muscles contributing to torque production about the radiohumeral joint
      during the pre- and posttests. Target-acquisition time decreased significantly
      with practice in most target directions and at both target torque levels. These
      performance improvements were primarily associated with increases in the peak
      rate of torque development after practice. At a muscular level, these changes
      were brought about by increases in the rates of recruitment of all agonist
      muscles. The spatiotemporal organization of muscle synergies was not
      significantly altered after practice. The observed adaptations appear to lead to
      performances that are generalizable to actions that require both greater and
      smaller joint torques than that practiced, and may be successfully recalled after
      a substantial period without practice. These results suggest that tasks in which
      performance is improved by increasing the rate of muscle activation, and thus the
      rate of joint torque development, may benefit in terms of the extent to which
      acquired levels of performance are maintained over time.

PMID- 15944231
TI  - Temperature compensation of neuromuscular modulation in aplysia.
AB  - Physiological systems that must operate over a range of temperatures often
      incorporate temperature-compensatory mechanisms to maintain their output within a
      relatively narrow, functional range of values. We analyze here an example in the
      accessory radula closer (ARC) neuromuscular system, a representative part of the
      feeding neuromusculature of the sea slug Aplysia. The ARC muscle's two motor
      neurons, B15 and B16, release, in addition to ACh that contracts the muscle,
      modulatory peptide cotransmitters that, through a complex network of effects in
      the muscle, shape the ACh-induced contractions. It is believed that this
      modulation is critical in optimizing the performance of the muscle for
      successful, efficient feeding behavior. However, previous work has shown that the
      release of the modulatory peptides from the motor neurons decreases dramatically
      with increasing temperature. From 15 to 25 degrees C, for example, release
      decreases 20-fold. Yet Aplysia live and feed successfully not only at 15 degrees
      C, but at 25 degrees C and probably at higher temperatures. Here, working with
      reduced B15/B16-ARC preparations in vitro as well as a mathematical model of the
      system, we have found a resolution of this apparent paradox. Although modulator
      release decreases 20-fold when the temperature is raised from 15 to 25 degrees C,
      the observed modulation of contraction shape does not decrease at all. Two
      mechanisms are responsible. First, further downstream within the modulatory
      network, the modulatory effects themselves-experimentally dissected by exogenous
      modulator application-have temperature dependencies opposite to that of modulator
      release, increasing with temperature. Second, the saturating curvature of the
      dose-response relations within the network diminishes the downstream impact of
      the decrease of modulator release. Thus two quite distinct mechanisms, one
      depending on the characteristics of the individual components of the network and
      the other emerging from the network's structure, combine to compensate for
      temperature changes to maintain the output of this physiological system.

PMID- 15944232
TI  - GABAergic control of the ascending input from the median raphe nucleus to the
      limbic system.
AB  - The median raphe nucleus (MRN) is the primary source of serotonergic afferents to
      the limbic system that are generally considered to suppress hippocampal theta
      oscillations. GABA receptors are expressed in the MRN by serotonergic and
      nonserotonergic cells, including GABAergic and glutamatergic neurons. This study
      investigated the mechanisms by which the fluctuating GABA tone in the MRN leads
      to induction or suppression of hippocampal theta rhythm. We found that MRN
      application of the GABA(A) agonist muscimol (0.05-1.0 mM) or GABA(B) agonist
      baclofen (0.2 mM) by reverse microdialysis had strong theta promoting effects.
      The GABA(A) antagonist bicuculline infused in low concentrations (0.1, 0.2 mM)
      eliminated theta rhythm. A short period of theta activity of higher than normal
      frequency preceded hippocampal desynchronization in 46% of rats. Bicuculline in
      larger concentrations (0.5, 1.0, 2.0 mM) resulted in a biphasic response of an
      initial short (<10 min) hippocampal desynchronization followed by stable theta
      rhythm that lasted as long as the infusion continued. The frequency and amplitude
      of theta waves were higher than in control recordings and the oscillations showed
      a conspicuous intermittent character. Hippocampal theta rhythm elicited by MRN
      administration of bicuculline could be completely (0.5 mM bicuculline) or
      partially (1.0 mM bicuculline) blocked by simultaneous infusion of the GABA(B)
      antagonist CGP35348. Our findings suggest that the GABAergic network may have two
      opposing functions in the MRN: relieving the theta-generators from serotonergic
      inhibition and regulating the activity of a theta-promoting circuitry by the
      fluctuating GABA tone. The two mechanisms may be involved in different functions.

PMID- 15944233
TI  - Mouse chromaffin cells have two populations of dense core vesicles.
AB  - The quantal hypothesis states that neurotransmitter is released in discrete
      packages, quanta, thought to represent the neurotransmitter content of individual
      vesicles. If true, then vesicle size should influence quantal size. Although
      chromaffin cells are generally thought to have a single population of secretory
      vesicles, our electron microscopy analysis suggested two populations as the size
      distribution was best described as the sum of two Gaussians. The average volume
      difference was fivefold. To test whether this difference in volume affected
      quantal size, neurotransmitter release from permeabilized cells exposed to 100
      microM Ca2+ was measured with amperometry. Quantal content was bimodally
      distributed with both large and small events; the distribution of vesicle sizes
      predicted by amperometry was extremely similar to those measured with electron
      microscopy. In addition, each population of events exhibited distinct release
      kinetics. These results suggest that chromaffin cells have two populations of
      dense core vesicles (DCV) with unique secretory properties and which may
      represent two distinct synthetic pathways for DCV biogenesis or alternatively
      they may represent different stages of biosynthesis.

PMID- 15944234
TI  - Visual responses of the human superior colliculus: a high-resolution functional
      magnetic resonance imaging study.
AB  - The superior colliculus (SC) is a multimodal laminar structure located on the
      roof of the brain stem. The SC is a key structure in a distributed network of
      areas that mediate saccadic eye movements and shifts of attention across the
      visual field and has been extensively studied in nonhuman primates. In humans, it
      has proven difficult to study the SC with functional MRI (fMRI) because of its
      small size, deep location, and proximity to pulsating vascular structures. Here,
      we performed a series of high-resolution fMRI studies at 3 T to investigate basic
      visual response properties of the SC. The retinotopic organization of the SC was
      determined using the traveling wave method with flickering checkerboard stimuli
      presented at different polar angles and eccentricities. SC activations were
      confined to stimulation of the contralateral hemifield. Although a detailed
      retinotopic map was not observed, across subjects, the upper and lower visual
      fields were represented medially and laterally, respectively. Responses were
      dominantly evoked by stimuli presented along the horizontal meridian of the
      visual field. We also measured the sensitivity of the SC to luminance contrast,
      which has not been previously reported in primates. SC responses were nearly
      saturated by low contrast stimuli and showed only small response modulation with
      higher contrast stimuli, indicating high sensitivity to stimulus contrast.
      Responsiveness to stimulus motion in the SC was shown by robust activations
      evoked by moving versus static dot stimuli that could not be attributed to eye
      movements. The responses to contrast and motion stimuli were compared with those
      in the human lateral geniculate nucleus. Our results provide first insights into
      basic visual responses of the human SC and show the feasibility of studying
      subcortical structures using high-resolution fMRI.

PMID- 15944235
TI  - Variability of swallowing performance in intact, freely feeding aplysia.
AB  - Variability in nervous systems is often taken to be merely "noise." Yet in some
      cases it may play a positive, active role in the production of behavior. The
      central pattern generator (CPG) that drives the consummatory feeding behaviors of
      Aplysia generates large, quasi-random variability in the parameters of the
      feeding motor programs from one cycle to the next; the variability then
      propagates through the firing patterns of the motor neurons to the contractions
      of the feeding muscles. We have proposed that, when the animal is faced with a
      new, imperfectly known feeding task in each cycle, the variability implements a
      trial-and-error search through the space of possible feeding movements. Although
      this strategy will not be successful in every cycle, over many cycles it may be
      the optimal strategy for feeding in an uncertain and changing environment. To
      play this role, however, the variability must actually appear in the feeding
      movements and, presumably, in the functional performance of the feeding behavior.
      Here we have tested this critical prediction. We have developed a technique to
      measure, in intact, freely feeding animals, the performance of Aplysia swallowing
      behavior, by continuously recording with a length transducer the movement of the
      seaweed strip being swallowed. Simultaneously, we have recorded with implanted
      electrodes activity at each of the internal levels, the CPG, motor neurons, and
      muscles, of the feeding neuromusculature. Statistical analysis of a large data
      set of these recordings suggests that functional performance is not determined
      strongly by one or a few parameters of the internal activity, but weakly by many.
      Most important, the internal variability does emerge in the behavior and its
      functional performance. Even when the animal is swallowing a long, perfectly
      regular seaweed strip, remarkably, the length swallowed from cycle to cycle is
      extremely variable, as variable as the parameters of the activity of the CPG,
      motor neurons, and muscles.

PMID- 15944236
TI  - Relationship between extraretinal component of firing rate and eye speed in area
      MST of macaque monkeys.
AB  - We have isolated extraretinal and retinal components of firing during smooth
      pursuit eye movements in the medial-superior-temporal area (MST) in the
      extrastriate visual cortex. Awake macaque monkeys tracked spots in total darkness
      to eliminate image motion inputs from the background. For 300 ms during sustained
      tracking at different speeds, the target was stabilized on the moving eye,
      practically eliminating image motion inputs from the tracking target. The
      extraretinal component of firing rate during image stabilization was direction
      selective and related to eye speed but sometimes showed a different preferred
      speed from the retinal component of the same neuron's responses. The highly
      variable firing rate of individual MST neurons allowed an ideal observer to
      predict target speed correctly on 25% of trials. Pooling the data from 71 MST
      neurons improved the correct response rate to 50%. Behavioral experiments imposed
      brief perturbations of target velocity to assess the gain of visual-motor
      transmission for pursuit. The average response to perturbations increased as a
      function of target speed. However, the size of the responses to individual
      perturbations allowed an ideal observer to predict target speed correctly on only
      35% of the trials. The imprecision of MST responses argues that the output of MST
      may be a poor candidate to drive eye velocity and so may instead regulate another
      component of pursuit. The good agreement between the eye velocity precision of
      the behavioral responses to perturbations of target motion and the firing of MST
      neurons raises regulation of the visual-motor gain of pursuit as one candidate
      component.

PMID- 15944237
TI  - Distinct mechanisms of presynaptic inhibition at GABAergic synapses of the rat
      substantia nigra pars compacta.
AB  - We investigated the mechanisms of presynaptic inhibition of GABAergic
      neurotransmission by group III metabotropic glutamate receptors (mGluRs) and
      GABA(B) receptors, in dopamine (DA) neurons of the substantia nigra pars compacta
      (SNc). Both the group III mGluRs agonist L-(+)-2-amino-4-phosphonobutyric acid
      (AP4, 100 microM) and the GABA(B) receptor agonist baclofen (10 microM)
      reversibly depressed the frequency of spontaneous inhibitory postsynaptic
      currents (sIPSCs) to 48.5 +/- 2.7 and 79.3 +/- 1.6% (means +/- SE) of control,
      respectively. On the contrary, the frequency of action potential-independent
      miniature IPSCs (mIPSCs), recorded in tetrodotoxin (TTX, 1 microM) and cadmium
      (100 microM) were insensitive to AP4 but were reduced by baclofen to 49.7 +/-
      8.6% of control. When the contribution of voltage-dependent calcium channels
      (VDCCs) to synaptic transmission was boosted with external barium (1 mM), AP4
      became effective in reducing TTX-resistant mIPSCs to 65.4 +/- 3.9% of control,
      thus confirming a mechanism of presynaptic inhibition involving modulation of
      VDCCs. Differently from AP4, baclofen inhibited to 58.5 +/- 6.7% of control the
      frequency mIPSCs recorded in TTX and the calcium ionophore ionomycin (2 microM),
      which promotes Ca2+-dependent, but VDCC-independent, transmitter release.
      Moreover, in the presence of alpha-latrotoxin (0.3 nM), to promote a Ca2+
      independent vesicular release of GABA, baclofen reduced mIPSC frequency to 48.1
      +/- 3.2% of control, while AP4 was ineffective. These results indicate that group
      III mGluRs depress GABA release to DA neurons of the SNc through inhibition of
      presynaptic VDCCs, while presynaptic GABA(B) receptors directly impair
      transmitter exocytosis.

PMID- 15944238
TI  - Evidence that long-term hyperexcitability of the sensory neuron soma induced by
      nerve injury in Aplysia is adaptive.
AB  - Peripheral axotomy induces long-term hyperexcitability (LTH) of centrally located
      sensory neuron (SN) somata in diverse species. In mammals this LTH can promote
      spontaneous activity of pain-related SNs, and such activity may contribute to
      neuropathic pain and hyperalgesia. However, few axotomized SN somata begin to
      fire spontaneously in any species, and why so many SNs display soma LTH after
      axotomy remains a mystery. Is soma LTH a side effect of injury with pathological
      but no adaptive consequences, or was this response selected during evolution for
      particular functions? A hypothesis for one function of soma LTH in nociceptive
      SNs in Aplysia californica is proposed: after peripheral injury that produces
      partial axotomy of some SNs, compensation for sensory deficits and protective
      sensitization are achieved by facilitating afterdischarge near the soma, which
      amplifies sensory input from injured peripheral fields. Four predictions of this
      hypothesis were confirmed in SNs that innervate the tail. First, LTH of SN somata
      was induced by a relatively natural axotomizing event-a small cut across part of
      the tail in the absence of anesthesia. Second, soma LTH was selectively expressed
      in SNs having axons in cut or crushed nerves rather than nearby, uninjured
      nerves. Third, after several weeks soma LTH began to reverse when functional
      recovery of the interrupted afferent pathway was shown by reestablishment of a
      centrally mediated siphon reflex. Fourth, axotomized SNs developed central
      afterdischarge that amplified sensory discharge coming from the periphery, and
      the after-depolarization underlying this afterdischarge was enhanced by previous
      axotomy.

PMID- 15944239
TI  - Competitive dynamics in cortical responses to visual stimuli.
AB  - Neurons in the visual cortex of the macaque monkey exhibit a variety of
      competitive behaviors, including normalization and oscillation, when presented
      with multiple visual stimuli. Here we argue that a biophysically plausible
      cortical circuit with opponent inhibition, spike-frequency adaptation, and
      synaptic depression can account for the full range of behaviors. The governing
      parameter is the strength of inhibition between competing neuronal pools. As the
      strength of inhibition is increased, the pattern of network behavior shifts from
      normalization mode to oscillatory mode, with oscillations occurring at
      progressively lower frequency until, at the extreme, winner-take-all behavior
      appears.

PMID- 15944240
TI  - Expression of estrogen receptor ESR1 and its 46-kDa variant in the gubernaculum
      testis.
AB  - Testicular descent corresponds to migration of the testis from the abdominal
      cavity to the scrotum and is essential for proper functioning of the testis.
      Recent advances in the characterization of estrogen receptor (ESR) subtypes and
      isoforms in various tissues prompted us to study ESRs within the gubernaculum
      testis, a structure involved in testicular descent. In the rat gubernaculum, we
      searched for ESR alpha (Esr1) and beta (Esr2) and for the androgen receptor (Ar),
      androgens being known to regulate testicular descent. Reverse transcription
      polymerase chain reaction (RT-PCR) revealed that Esr1, Esr2, and Ar mRNAs were
      all expressed in the gubernaculum. Using PEETA (Primer extension,
      Electrophoresis, Elution, Tailing, and Amplification), we established that all
      Esr1 leader exons, previously identified in other organs, such as the uterus and
      pituitary, were transcribed in the gubernaculum, with the major form being O/B.
      The RNA protection assays, RT-PCR, and Western blot experiments revealed that
      isoform-specific mRNA transcripts generated by alternative splicing of the C
      leader sequence on coding exons 1 and 2 of the Esr1 gene gave the 46- and 66-kDa
      ESR1 proteins. The ESR1 and AR proteins were found to colocalize in the
      parenchymal cells of the gubernaculum early in development, whereas AR also was
      strongly expressed in the muscular cells, both during fetal and postnatal life.
      The ESR2 protein was weakly expressed, principally in the muscular cells, but
      only once testicular descent had occurred. The levels of the 46-kDa ESR1 variant
      (ER46) exceeded those of the 66-kDa ESR1 form (ER66) at periods when the
      gubernaculum developed. Conversely, the 66-kDa form appears to predominate
      clearly when the gubernaculum growth was low or completed. The possible role of
      estrogens on the modulation of the androgen-dependent growth of the gubernaculum
      and, more widely, on testicular descent is discussed.

PMID- 15944241
TI  - Matrix metalloproteinases in endometrial breakdown and repair: functional
      significance in a mouse model.
AB  - Considerable correlative evidence suggests an important role for matrix
      metalloproteinases (MMPs) in menstruation, a process which occurs naturally in
      very few species. In this study, MMP expression was examined in a mouse model of
      endometrial breakdown and repair and the functional importance of MMPs
      determined. In the model, progesterone support was withdrawn from mice in which
      endometrial decidualization had been induced; 24 h later, endometrial breakdown
      was complete, and the entire decidual zone had been shed. Re-epithelialization
      had occurred by 36 h, and the endometrium had undergone extensive restoration
      toward a predecidualized state by 48 h. Immunoreactive MMP9 and MMP7 colocalized
      with leukocyte subsets, particularly neutrophils, whereas MMP13 staining was
      always extracellular. MMP3 and MMP7 were abundant during re-epithelialization in
      close proximity to newly reforming epithelium. The functional importance of MMPs
      in these processes was examined using two MMP inhibitors, doxycycline and
      batimistat. Both inhibitors effectively reduced MMP activity, as assessed by in
      situ zymography, but did not have significant effects on endometrial breakdown or
      repair. This study demonstrates that although MMPs are present in abundance
      during endometrial breakdown and repair in this mouse model, they are not the key
      mediators of these processes.

PMID- 15944242
TI  - Mice deficient in CHRNA7, a subunit of the nicotinic acetylcholine receptor,
      produce sperm with impaired motility.
AB  - In this study we investigate the role of the CHRNA7 subunit (also known as the
      alpha7 subunit) of the nicotinic acetylcholine receptor in mouse sperm function.
      We confirm by reverse-transcription-polymerase chain reaction the expression in
      adult mouse testis of Chrna7 mRNA and demonstrate the subunit's presence in mouse
      sperm by immunoblot. Alpha-bungarotoxin binds a range of nicotinic acetylcholine
      receptor subunits, including the CHRNA7 subunit. Localization studies using a
      fluorescent alpha-bungarotoxin-tetramethyl-rhodamine conjugate revealed specific
      binding sites on the midpiece of mouse sperm with fainter alpha-bungarotoxin
      binding on the remainder of the flagellum. Mice engineered with a double-null
      disruption of the Chrna7 gene displayed only faint fluorescence on the midpiece,
      suggesting that the CHRNA7 contributed the majority of the observed alpha
      bungarotoxin binding sites. The location of alpha-bungarotoxin binding suggested
      that nicotinic acetylcholine receptors may play an ionotropic role in sperm
      motility. Sperm from Chrna7(-/-) mice display no difference in number,
      morphology, viability or spontaneous acrosome reaction rate compared with
      Chrna7(+/+) sperm. Studies using computer-assisted sperm analysis indicate the
      motility of Chrna7(-/-) sperm is significantly impaired. This impairment is
      characterized by significantly reduced swimming velocities, failure to maintain
      vigorous swimming, and lower levels of hyperactivated swimming patterns in
      Chrna7(-/-) sperm compared with Chrna7(+/+) sperm. This is the first genetic
      evidence that sperm nicotinic acetylcholine receptors are important for
      maintenance of normal sperm motility.

PMID- 15944243
TI  - Evidence for a role of mitogen-activated protein kinase 3/mitogen-activated
      protein kinase in the development of testicular ischemia-reperfusion injury.
AB  - Mitogen-activated protein kinase (MAPK) 3/MAPK1 (also known as ERK1/ERK2) plays
      an important role in the signal transduction pathways. To our knowledge, however,
      its role in the development of testicular ischemia-reperfusion injury has not yet
      been investigated. Therefore, we studied the pattern of MAPK3/MAPK1 activation in
      a experimental model of testicular ischemia-reperfusion injury. We also
      investigated MAPK8 to understand whether an association exists between these two
      MAPKs. Adult male Sprague-Dawley rats were subjected to 1 h of testicular
      ischemia followed by 24 h of reperfusion or to a sham testicular ischemia
      reperfusion. Animals were randomized to receive PD98059, which is an inhibitor of
      MAPK3/MAPK1 (10 mg/kg i.p. administered immediately after detorsion), or its
      vehicle. The time course of MAPK3/MAPK1, MAPK8, and tumor necrosis factor (TNF;
      also known as TNF alpha) expression and a histological examination in both the
      ischemic-reperfused testis and the contralateral one were performed. In both
      testes, MAPK3/MAPK1 and MAPK8 expression appeared following 10 min of reperfusion
      and reached their highest activation after 30 min. The MAPK levels slowly
      decreased, and no significant expression of either kinase was observed following
      2 h of reperfusion. Expression of TNF was evident after 1 h of reperfusion and
      reached its maximum increase after 3 h. PD98059 blunted MAPK3/MAPK1 and MAPK8,
      reduced TNF expression, and improved the testicular damage caused by ischemia
      reperfusion injury in both testes. These data emphasize that MAPK3/MAPK1 has a
      role in testicular damage and that its blockade might have a future therapeutic
      role for the management of patients with unilateral testicular torsion.

PMID- 15944244
TI  - Agonist activity of the small molecule C3aR ligand SB 290157.

PMID- 15944245
TI  - Infections and autoimmunity--good or bad?
AB  - The relationship between infections and autoimmunity is complex. Current evidence
      indicates that microbes can initiate, enhance, or, conversely, abrogate
      autoimmunity. In this paper, we will review experimental examples illustrating
      mechanisms involved in these three scenarios. Microbial infections can act as
      environmental triggers inducing or promoting autoimmunity resulting in clinical
      manifestations of autoimmune disease in genetically predisposed individuals.
      However, increasing evidence suggests the opposite outcome, which is the
      prevention or amelioration of autoimmune processes following microbial
      encounters. These latter observations support conceptually the "hygiene
      hypothesis," suggesting that cleaner living conditions will lead to enhanced
      incidence of autoimmune disorders, asthma, and allergies. Because proof of
      concept in humans is difficult to obtain, we will discuss relevant animal model
      data in context with likely or proven human associations. Knowledge of mechanisms
      that underlie either positive or negative effects of infections on autoimmunity
      will facilitate exploration of molecular details for prospective clinical studies
      in the future.

PMID- 15944246
TI  - Cutting edge: CD4+CD25+ regulatory T cells impaired for intestinal homing can
      prevent colitis.
AB  - Transfer of CD4(+)CD45RB(high) T cells into RAG(-/-) mice causes colitis, which
      can be prevented by CD4(+)CD25(+) regulatory T cells (Treg). Colitis induction by
      CD4(+)CD45RB(high) T cells requires beta(7) integrin-dependent intestinal
      localization, but the importance of beta(7) integrins for Treg function is
      unknown. In this study, we show that beta(7)(-/-) Treg were effective in
      preventing colitis. Treg expanded in vivo to the same extent as
      CD4(+)CD45RB(high) T cells after transfer and they did not inhibit
      CD4(+)CD45RB(high) T cell expansion in lymphoid tissues, although they prevented
      the accumulation of Th1 effector cells in the intestine. beta(7)(-/-) Treg were
      significantly reduced in the large intestine, however, compared with wild-type
      Treg, and regulatory activity could not be recovered from the intestine of
      recipients of beta(7)(-/-) Treg. These data demonstrate that Treg can prevent
      colitis by inhibiting the accumulation of tissue-seeking effector cells and that
      Treg accumulation in the intestine is dispensable for colitis suppression.

PMID- 15944247
TI  - Cutting edge: egress of newly generated plasma cells from peripheral lymph nodes
      depends on beta 2 integrin.
AB  - During humoral immune responses, naive B cells differentiate into Ab-secreting
      plasma cells within secondary lymphoid organs. Differentiating plasma cells
      egress from their sites of generation and redistribute to other tissues,
      predominantly the bone marrow and mucosal tissues. In this study, we demonstrate
      that within peripheral lymph nodes newly generated plasma cells localize to
      medullary cords which express the beta(2) integrin ligand ICAM-1. In beta(2)
      integrin-deficient mice plasma cells accumulate inside the lymph nodes, resulting
      in severely reduced plasma cell numbers in the bone marrow. Since plasma cells
      isolated from beta(2) integrin-deficient animals migrate efficiently into the
      bone marrow when transferred i.v., our findings provide profound evidence that
      beta(2) integrins are required for the egress of plasma cells from peripheral
      lymph nodes.

PMID- 15944248
TI  - A new dynamic model of CD8+ T effector cell responses via CD4+ T helper-antigen
      presenting cells.
AB  - A long-standing paradox in cellular immunology has been the conditional
      requirement for CD4(+) Th cells in priming of CD8(+) CTL responses. We propose a
      new dynamic model of CD4(+) Th cells in priming of Th-dependent CD8(+) CTL
      responses. We demonstrate that OT II CD4(+) T cells activated by OVA-pulsed
      dendritic cells (DC(OVA)) are Th1 phenotype. They acquire the immune synapse
      composed MHC II/OVAII peptide complexes and costimulatory molecules (CD54 and
      CD80) as well as the bystander MHC class I/OVAI peptide complexes from the
      DC(OVA) by DC(OVA) stimulation and thus also the potential to act themselves as
      APCs. These CD4(+) Th-APCs stimulate naive OT I CD8(+) T cell proliferation
      through signal 1 (MHC I/OVAI/TCR) and signal 2 (e.g., CD54/LFA-1 and CD80/CD28)
      interactions and IL-2 help. In vivo, they stimulate CD8(+) T cell proliferation
      and differentiation into CTLs and induce effective OVA-specific antitumor
      immunity. Taken together, this study demonstrates that CD4(+) Th cells carrying
      acquired DC Ag-presenting machinery can, by themselves, efficiently stimulate CTL
      responses. These results have substantial implications for research in antitumor
      and other aspects of immunity.

PMID- 15944249
TI  - Release of high mobility group box 1 by dendritic cells controls T cell
      activation via the receptor for advanced glycation end products.
AB  - High mobility group box 1 (HMGB1) is an abundant and conserved nuclear protein
      that is released by necrotic cells and acts in the extracellular environment as a
      primary proinflammatory signal. In this study we show that human dendritic cells,
      which are specialized in Ag presentation to T cells, actively release their own
      HMGB1 into the extracellular milieu upon activation. This secreted HMGB1 is
      necessary for the up-regulation of CD80, CD83, and CD86 surface markers of human
      dendritic cells and for IL-12 production. The HMGB1 secreted by dendritic cells
      is also required for the clonal expansion, survival, and functional polarization
      of naive T cells. Using neutralizing Abs and receptor for advanced glycation end
      product-deficient (RAGE(-/-)) cells, we demonstrate that RAGE is required for the
      effect of HMGB1 on dendritic cells. HMGB1/RAGE interaction results in downstream
      activation of MAPKs and NF-kappaB. The use of an ancient signal of necrosis,
      HMGB1, by dendritic cells to sustain their own maturation and for activation of T
      lymphocytes represents a profitable evolutionary mechanism.

PMID- 15944250
TI  - Local radiation therapy of B16 melanoma tumors increases the generation of tumor
      antigen-specific effector cells that traffic to the tumor.
AB  - Immunotherapy of cancer is attractive because of its potential for specificity
      and limited side effects. The efficacy of this approach may be improved by
      providing adjuvant signals and an inflammatory environment for immune cell
      activation. We evaluated antitumor immune responses in mice after treatment of
      OVA-expressing B16-F0 tumors with single (15 Gy) or fractionated (5 x 3 Gy) doses
      of localized ionizing radiation. Irradiated mice had cells with greater
      capability to present tumor Ags and specific T cells that secreted IFN-gamma upon
      peptide stimulation within tumor-draining lymph nodes than nonirradiated mice.
      Immune activation in tumor-draining lymph nodes correlated with an increase in
      the number of CD45(+) cells infiltrating single dose irradiated tumors compared
      with nonirradiated mice. Similarly, irradiated mice had increased numbers of
      tumor-infiltrating lymphocytes that secreted IFN-gamma and lysed tumor cell
      targets. Peptide-specific IFN-gamma responses were directed against both the
      class I and class II MHC-restricted OVA peptides OVA(257-264) and OVA(323-339),
      respectively, as well as the endogenous class I MHC-restricted B16 tumor peptide
      tyrosinase-related protein 2(180-188). Adoptive transfer studies indicated that
      the increased numbers of tumor Ag-specific immune cells within irradiated tumors
      were most likely due to enhanced trafficking of these cells to the tumor site.
      Together these results suggest that localized radiation can increase both the
      generation of antitumor immune effector cells and their trafficking to the tumor
      site.

PMID- 15944251
TI  - HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL
      response.
AB  - Mutational escape from the CTL response represents a major driving force for
      viral diversification in HIV-1-infected adults, but escape during infancy has not
      been described previously. We studied the immune response of perinatally infected
      children to an epitope (B57-TW10) that is targeted early during acute HIV-1
      infection in adults expressing HLA-B57 and rapidly mutates under this selection
      pressure. Viral sequencing revealed the universal presence of escape mutations
      within TW10 among B57- and B5801-positive children. Mutations in TW10 and other
      B57-restricted epitopes arose early following perinatal infection of B57-positive
      children born to B57-negative mothers. Surprisingly, the majority of B57/5801
      positive children exhibited a robust response to the TW10 escape variant while
      recognizing the wild-type epitope weakly or not at all. These data demonstrate
      that children, even during the first years of life, are able to mount functional
      immune responses of sufficient potency to drive immune escape. Moreover, our data
      suggest that the consequences of immune escape may differ during infancy because
      most children mount a strong variant-specific immune response following escape,
      which is rarely seen in adults. Taken together, these findings indicate that the
      developing immune system of children may exhibit greater plasticity in responding
      to a continually evolving chronic viral infection.

PMID- 15944252
TI  - Macrophage colony-stimulating factor induces vascular endothelial growth factor
      production in skeletal muscle and promotes tumor angiogenesis.
AB  - Although M-CSF has been used for myelosuppression due to chemotherapy in patients
      with solid tumors, the effect of exogenous M-CSF on tumor angiogenesis has not
      been studied. In this study we showed that M-CSF has the ability to accelerate
      solid tumor growth by enhancing angiogenesis with a novel mechanism. M-CSF
      accelerated intratumoral vessel density in tumors inoculated into mice, although
      it did not accelerate the proliferation of malignant cells and cultured
      endothelial cells in vitro. In both the absence and the presence of tumors, M-CSF
      significantly increased the circulating cells that displayed phenotypic
      characteristics of endothelial progenitor cells in mice. Moreover, M-CSF
      treatment induced the systemic elevation of vascular endothelial growth factor
      (VEGF). VEGFR-2 kinase inhibitor significantly impaired the effect of M-CSF on
      tumor growth. In vivo, M-CSF increased VEGF mRNA expression in skeletal muscles.
      Even after treatment with carageenan and anti-CD11b mAb in mice, M-CSF increased
      VEGF production in skeletal muscles, suggesting that systemic VEGF elevation was
      attributed to skeletal muscle VEGF production. In vitro, M-CSF increased VEGF
      production and activated the Akt signaling pathway in C2C12 myotubes. These
      results suggest that M-CSF promotes tumor growth by increasing endothelial
      progenitor cells and activating angiogenesis, and the effects of M-CSF are
      largely based on the induction of systemic VEGF from skeletal muscles.

PMID- 15944253
TI  - Activation of CD8+ regulatory T cells by human placental trophoblasts.
AB  - The immunological basis by which a mother tolerates her semi-allogeneic fetus
      remains poorly understood. Several mechanisms are likely to contribute to this
      phenomenon including active immune regulation by regulatory T cells. In this
      article, we report that human placental trophoblasts activate a clonal population
      of CD8(+) T cells with regulatory function. These cells are not MHC class I
      restricted, but require costimulation through a member of the carcinoembryonic Ag
      family present on early gestation trophoblasts. These regulatory T cells express
      the mucosal markers CD101 and CD103 and display selective usage of the TCR gene
      Vbeta9. CD8(+) T cells isolated from the peripheral blood of pregnant mothers (16
      28 wk) also demonstrate expansions in the same Vbeta family (Vbeta9), signaling a
      possible role for these cells in preventing fetal rejection in vivo. We have
      previously characterized a subset of CD8(+) regulatory T cells activated by the
      combination of the nonclassical class I molecule CD1d and a costimulatory
      molecule of the carcinoembryonic Ag family present on the intestinal epithelium.
      These data support the concept that distinct regulatory T cell populations exist
      at different sites and may be regulated locally by unique restriction elements,
      costimulatory signals, and Ags.

PMID- 15944254
TI  - A defective viral superantigen-presenting phenotype in HLA-DR transfectants is
      corrected by CIITA.
AB  - Activation of T lymphocytes by mouse mammary tumor virus superantigen (vSAg)
      requires binding to MHC class II molecules. The subcellular location where
      functional interactions occur between MHC class II molecules and vSAgs is still a
      matter of debate. To gain further insight into this issue, we have used human
      epithelial HeLa cells expressing HLA-DR1. Surprisingly, the human cells were
      unable to present transfected vSAg7 or vSAg9 to a series of murine T cell
      hybridomas. The defect is not related to a lack of vSAg processing, because these
      cells can indirectly activate T cells after coculture in the presence of B
      lymphocytes. However, after IFN-gamma treatment, the HeLa DR1(+) cells became apt
      at directly presenting the vSAg. Furthermore, transfection of CIITA was
      sufficient to restore presentation. Reconstitution experiments demonstrated the
      necessity of coexpressing HLA-DM and invariant chain (Ii) for efficient vSAg
      presentation. Interestingly, inclusion of a dileucine motif in the DRbeta
      cytoplasmic tail bypassed the need for HLA-DM expression and allowed the
      efficient presentation of vSAg7 in the presence of Ii. A similar trafficking
      signal was included in vSAg7 by replacing its cytoplasmic tail with the one of
      Ii. However, sorting of this chimeric Ii/vSAg molecule to the endocytic pathway
      completely abolished both its indirect and direct presentation. Together, our
      results suggest that functional vSAgs-DR complexes form after the very late
      stages of class II maturation, most probably at the cell surface.

PMID- 15944255
TI  - TLR2 agonist ameliorates established allergic airway inflammation by promoting
      Th1 response and not via regulatory T cells.
AB  - TLRs are primary sensors of both innate and adaptive immune systems, where they
      play a pivotal role in the response directed against structurally conserved
      components of pathogens. Synthetic bacterial lipopeptide Pam3CSK4 is a TLR2
      agonist capable of modulating Th1 and Th2 responses. This study examines the
      therapeutic effect of Pam3CSK4 in established airway inflammation in a murine
      model of asthma. In mice previously sensitized and challenged with OVA, Pam3CSK4
      given i.p. markedly reduced the total inflammatory cell infiltrate and
      eosinophilia in bronchoalveolar lavage fluid. Pam3CSK4 therapy was associated
      with a reduction in OVA-induced IL-4 and IL-5 secretion from thoracic lymph node
      culture, airways inflammation, bronchial hyperresponsiveness, and serum levels of
      IgE. Pam3CSK4 therapy was also associated with an increase in OVA-induced IFN
      gamma, IL-12, and IL-10 production. However, the anti-inflammatory effect of
      Pam3CSK4 was independent of IL-10 or TGF-beta, but was critically dependent on IL
      12, the production of which by dendritic cells was enhanced by Pam3CSK4 in vitro.
      Our results provide direct evidence that Pam3CSK4 could represent a novel
      therapeutic agent in allergic airways disease.

PMID- 15944256
TI  - A class I transgene reveals regulatory events on chromosome 1 marking peripheral
      T cell differentiation and memory.
AB  - T cells respond to external signals by altering patterns of gene expression. Our
      characterization of a transgenic mouse revealed a genetic locus that is
      specifically regulated in T cells. Elucidation of the factors controlling the
      expression of the marker transgene may reveal basic regulatory mechanisms used by
      T cells as they differentiate from naive to primed/memory T cells. Although
      endogenous MHC class I K(q) expression is normal in these animals, expression of
      the K(b) transgene differentiates naive from primed/memory T cells. K(bHigh) T
      cells bear the phenotypic and functional properties of primed/memory T cells,
      while K(bLow) T cells have naive phenotypes. The transition from K(bLow) to
      K(bHigh) appears to involve signals resulting from engagement of the TCR. We show
      that transgene integration has occurred on chromosome 1, between D1Mit365 and
      D1Mit191. The gene regulatory mechanisms directing expression of the locus marked
      by the transgene are distinct from those controlling other known T cell-related
      genes within this locus. Stimulation of K(bHigh) T cells results in the up
      regulation of both the endogenous K(q) gene and the K(b) transgene. However, the
      same stimuli induce increased expression of only K(q) on K(bLow) T cells. This
      indicates that even though the transcription factors necessary for class I
      expression are present in K(bLow) T cells, the K(b) gene appears not to be
      accessible to these factors. These findings suggest a change in chromatin
      structure at the transgene integration site as cells progress from a naive to a
      primed/memory differentiation state.

PMID- 15944257
TI  - CD27/CFSE-based ex vivo selection of highly suppressive alloantigen-specific
      human regulatory T cells.
AB  - Naturally occurring CD4(+)CD25(+) regulatory T cells (Treg) are crucial in
      immunoregulation and have great therapeutic potential for immunotherapy in the
      prevention of transplant rejection, allergy, and autoimmune diseases. The
      efficacy of Treg-based immunotherapy critically depends on the Ag specificity of
      the regulatory T cells. Moreover, the use of Ag-specific Treg as opposed to
      polyclonal expanded Treg will reduce the total number of Treg necessary for
      therapy. Hence, it is crucial to develop ex vivo selection procedures that allow
      selection and expansion of highly potent, Ag-specific Treg. In this study we
      describe an ex vivo CFSE cell sorter-based isolation method for human alloantigen
      specific Treg. To this end, freshly isolated CD4(+)CD25(+) Treg were labeled with
      CFSE and stimulated with (target) alloantigen and IL-2 plus IL-15 in short-term
      cultures. The alloantigen-reactive dividing Treg were characterized by low CFSE
      content and could be subdivided by virtue of CD27 expression. CD27/CFSE cell
      sorter-based selection of CD27(+) and CD27(-) cells resulted in two highly
      suppressive Ag-specific Treg subsets. Each subset suppressed naive and Ag
      experienced memory T cells, and importantly, CD27(+) Treg also suppressed ongoing
      T cell responses. Summarizing, the described procedure enables induction,
      expansion, and especially selection of highly suppressive, Ag-specific Treg
      subsets, which are crucial in Ag-specific, Treg-based immunotherapy.

PMID- 15944258
TI  - Tetrahydro-4-aminobiopterin attenuates dendritic cell-induced T cell priming
      independently from inducible nitric oxide synthase.
AB  - Formation of NO by NO synthases (NOSs) strictly depends on tetrahydrobiopterin.
      Its structural analog, tetrahydro-4-aminobiopterin, is an inhibitor of all NOS
      isoenzymes, which prolongs allograft survival in acute murine cardiac rejection
      and prevents septic shock in the rat. In this study, we show that murine bone
      marrow-derived dendritic cells treated with tetrahydro-4-aminobiopterin had a
      reduced capacity to prime alloreactive murine T cells in oxidative mitogenesis.
      Checking for a possible influence on LPS-induced dendritic cell maturation, we
      found that tetrahydro-4-aminobiopterin down-regulated MHC class II expression and
      counteracted LPS-induced down-regulation of ICOS ligand, while expression of
      CD40, CD86, CD80, B7-H1, and B7-DC remained unchanged. Tetrahydro-4
      aminobiopterin also reduced activation of CD4(+) T cells isolated from mice
      overexpressing an OVA-specific TCR by OVA-loaded murine bone marrow-derived
      dendritic cells, thus indicating that its effect on MHC class II expression is
      involved in attenuating T cell activation. In line with affecting dendritic cell
      function and T cell activation, tetrahydro-4-aminobiopterin impaired production
      of proinflammatory cytokines and the Th1 response. With regard to cell survival,
      tetrahydro-4-aminobiopterin induced efficient apoptosis of murine T cells but not
      of murine dendritic cells. Experiments with cells from inducible NOS (iNOS)
      knockout mice and with N(6)-(1-iminoethyl)-L-lysine, a specific inhibitor of
      iNOS, ruled out participation of iNOS in any of the observed effects. These
      findings characterize attenuation of T cell stimulatory capacity of murine bone
      marrow-derived dendritic cells as an immunosuppressive mechanism of tetrahydro-4
      aminobiopterin that is not related to its iNOS-inhibiting properties.

PMID- 15944259
TI  - TCR engagement increases hypoxia-inducible factor-1 alpha protein synthesis via
      rapamycin-sensitive pathway under hypoxic conditions in human peripheral T cells.
AB  - Peripheral T cells encounter rapid decrease in oxygen tension because they are
      activated by Ag recognition and migrate into inflammatory sites or tumors.
      Activated T cells, therefore, are thought to have such machineries that enable
      them to adapt to hypoxic conditions and execute immune regulation in situ. We
      have recently shown that survival of CD3-engaged human peripheral blood T cells
      is prolonged under hypoxic conditions and hypoxia-inducible factor-1 (HIF-1) and
      its target gene product adrenomedullin play a critical role for the process. It
      is also shown that hypoxia alone is not sufficient, but TCR-mediated signal is
      required for accumulation of HIF-1alpha in human peripheral T cells. In the
      present study, we showed that TCR engagement does not influence hypoxia-dependent
      stabilization but stimulates protein synthesis of HIF-1alpha, most possibly via
      PI3K/mammalian target of rapamycin system, and that expression of HIF-1alpha and
      its target genes is blocked by treatment with rapamycin. Since some of those gene
      products, e.g., glucose transporters and phosphoglycerokinase, are considered to
      be essential for glycolysis and energy production under hypoxic conditions and
      adequate immune reaction in T cells, this TCR-mediated synthesis of HIF-1alpha
      may play a pivotal role in peripheral immune response. Taken together, our
      results may highlight a novel aspect of downstream signal from Ag recognition by
      TCR and a unique pharmacological role of rapamycin as well.

PMID- 15944260
TI  - The role of host CD4 T cells in the pathogenesis of the chronic graft-versus-host
      model of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is characterized by production of autoantibodies and
      glomerulonephritis. The murine chronic graft-vs-host (cGVH) model of systemic
      lupus erythematosus is induced by allorecognition of foreign MHC class II
      determinants. Previous studies have shown that cGVH could not be induced in CD4
      knockout (CD4KO) mice. We have further explored the role of host CD4 T cells in
      this model. Our studies now show that B cells in CD4KO mice have intrinsic
      defects that prevent them from responding to allohelp. In addition, B cells in
      CD4KO mice showed phenotypic differences compared with congeneic C57BL/6 B cells,
      indicating some degree of in vivo activation and increased numbers of cells
      bearing a marginal zone B cell phenotype. The transfer of syngeneic CD4 T cells
      at the time of initiation of cGVH did not correct these B cell abnormalities;
      however, if CD4 T cells were transferred during the development and maturation of
      B cells, then the B cells from CD4KO mice acquire the ability to respond in cGVH.
      These studies clearly indicate that B cells need to coexist with CD4 T cells
      early in their development to develop full susceptibility to alloactivation
      signals.

PMID- 15944261
TI  - Recombinant p21 protein inhibits lymphocyte proliferation and transcription
      factors.
AB  - Cellular proliferation determines the events leading to the initiation and
      development of inflammation, immune activation, cancer, atherogenesis, and other
      disorders associated with aberrant cell proliferation. Cyclin inhibitor p21 plays
      a unique role in limiting cell cycle progression. However, its effectiveness can
      only be demonstrated with direct in vitro and in vivo delivery to control
      aberrant proliferation. We demonstrate that using a protein-transducing domain
      p21 protein a) localizes within the nuclear compartments of cells, b) interacts
      with transcription factors, NF-kappaB, and NFATs (NFATc and NFATp), and c)
      inhibits lymphocyte proliferation and expression of proinflammatory cytokines.
      This study using lymphocyte proliferation as a model suggests that the
      recombinant p21 protein can directly be delivered as a therapeutic protein to
      provide a novel, viable, and powerful strategy to limit proliferation,
      inflammation, alloimmune activation, cancer, and vascular proliferative disorders
      such as atherosclerosis.

PMID- 15944262
TI  - Circadian oscillations of clock genes, cytolytic factors, and cytokines in rat NK
      cells.
AB  - A growing body of knowledge is revealing the critical role of circadian
      physiology in the development of specific pathological entities such as cancer.
      NK cell function participates in the immune response against infection and
      malignancy. We have reported previously the existence of a physiological
      circadian rhythm of NK cell cytolytic activity in rats, suggesting the existence
      of circadian mechanisms subjacent to NK cell function. At the cellular level,
      circadian rhythms are originated by the sustained transcriptional-translational
      oscillation of clock genes that form the cellular clock apparatus. Our aim in
      this study was to investigate the presence of molecular clock mechanisms in NK
      cells as well as the circadian expression of critical factors involved in NK cell
      function. For that purpose, we measured the circadian changes in the expression
      of clock genes (Per1, Per2, Bmal1, Clock), Dbp (a clock-controlled output gene),
      CREB (involved in clock signaling), cytolytic factors (granzyme B and perforin),
      and cytokines (IFN-gamma and TNF-alpha) in NK cells enriched from the rat spleen.
      The results obtained from this study demonstrate for the first time the existence
      of functional molecular clock mechanisms in NK cells. Moreover, the circadian
      expression of cytolytic factors and cytokines in NK cells reported in this study
      emphasizes the circadian nature of NK cell function.

PMID- 15944263
TI  - Peptide-specific CD8 T regulatory cells use IFN-gamma to elaborate TGF-beta-based
      suppression.
AB  - We identified a murine peptide-specific CD8 T regulatory cell population able to
      suppress responding CD4 T cells. Immunization with OVA, poly(I:C), and anti-4-1BB
      generated a population of SIINFEKL-specific CD8 T regulatory cells that
      profoundly inhibited peptide-responding CD4 T cells from cellular division. The
      mechanism of suppression required IFN-gamma, but IFN-gamma alone was not
      sufficient to suppress the responding CD4 T cells. The data show that CD8 T
      regulatory cells were unable to suppress unless they engaged IFN-gamma.
      Furthermore, even in the absence of recall with peptide, the CD8 T regulatory
      cells suppressed CD4 responses as long as IFN-gamma was present. To examine the
      effector mechanism of suppression, we showed that neutralizing TGF-beta inhibited
      suppression because inclusion of anti-TGF-beta rescued the proliferative capacity
      of the responding cells. TGF-beta-based suppression was dependent completely upon
      the CD8 T regulatory cells being capable of binding IFN-gamma. This was the case,
      although peptide recall of primed IFN-gamma (-/-) or IFN-gammaR(-/-) CD8 T cells
      up-regulated pro-TGF-beta protein as measured by surface latency-associated
      peptide expression but yet were unable to suppress. Finally, we asked whether the
      CD8 T regulatory cells were exposed to active TGF-beta in vivo and showed that
      only wild-type CD8 T regulatory cells expressed the TGF-beta-dependent biomarker
      CD103, suggesting that latency-associated peptide expression is not always
      congruent with elaboration of active TGF-beta. These data define a novel
      mechanism whereby IFN-gamma directly stimulates CD8 T regulatory cells to
      elaborate TGF-beta-based suppression. Ultimately, this mechanism may permit
      regulation of pathogenic Th1 responses by CD8 T regulatory cells.

PMID- 15944264
TI  - Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by
      antioxidative vitamins generates regulatory T cells.
AB  - Dendritic cells (DCs) are central to T cell immunity, and many strategies have
      been used to manipulate DCs to modify immune responses. We investigated the
      effects of antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) on
      DC phenotype and function. Vitamins C and E are both antioxidants, and concurrent
      use results in a nonadditive activity. We have demonstrated that DC treated with
      these antioxidants are resistant to phenotypic and functional changes following
      stimulation with proinflammatory cytokines. Following treatment, the levels of
      intracellular oxygen radical species were reduced, and the protein kinase RNA
      regulated, eukaryotic translation initiation factor 2alpha, NF-kappaB, protein
      kinase C, and p38 MAPK pathways could not be activated following inflammatory
      agent stimulation. We went on to show that allogeneic T cells (including
      CD4(+)CD45RO, CD4(+)CD45RA, and CD4(+)CD25(-) subsets) were anergized following
      exposure to vitamin-treated DCs, and secreted higher levels of Th2 cytokines and
      IL-10 than cells incubated with control DCs. These anergic T cells act as
      regulatory T cells in a contact-dependent manner that is not dependent on IL-4,
      IL-5, IL-10, IL-13, and TGF-beta. These data indicate that vitamin C- and E
      treated DC might be useful for the induction of tolerance to allo- or
      autoantigens.

PMID- 15944265
TI  - IL-4 modulation of CD4+CD25+ T regulatory cell-mediated suppression.
AB  - Murine CD4(+)CD25(+) T regulatory (Treg) cells were cocultured with CD4(+)CD25(-)
      Th cells and APCs or purified B cells and stimulated by anti-CD3 mAb. Replacement
      of APCs by B cells did not significantly affect the suppression of CD4(+)CD25(-)
      Th cells. When IL-4 was added to separate cell populations, this cytokine
      promoted CD4(+)CD25(-) Th and CD4(+)CD25(+) Treg cell proliferation, whereas the
      suppressive competence of CD4(+)CD25(+) Treg cells was preserved. Conversely, IL
      4 added to coculture of APCs, CD4(+)CD25(-) Th cells, and CD4(+)CD25(+) Treg
      cells inhibited the suppression of CD4(+)CD25(-) Th cells by favoring their
      survival through the induction of Bcl-2 expression. At variance, suppression was
      not affected by addition of IL-13, although this cytokine shares with IL-4 a
      receptor chain. When naive CD4(+)CD25(-) Th cells were replaced by Th1 and Th2
      cells, cell proliferation of both subsets was equally suppressed, but suppression
      was less pronounced compared with that of CD4(+)CD25(-) Th cells. IL-4 production
      by Th2 cells was also inhibited. These results indicate that although
      CD4(+)CD25(+) Treg cells inhibit IL-4 production, the addition of IL-4
      counteracts CD4(+)CD25(+) Treg cell-mediated suppression by promoting CD4(+)CD25(
      ) Th cell survival and proliferation.

PMID- 15944266
TI  - CD8 cell division maintaining cytotoxic memory occurs predominantly in the bone
      marrow.
AB  - Long-term persistence of Ag-experienced CD8 cells, a class of T lymphocytes with
      cytotoxic function, contributes to immunological memory against intracellular
      pathogens. After Ag clearance, memory CD8 cells are maintained over time by a
      slow proliferation, primarily cytokine driven. In this article, we show that the
      bone marrow (BM) is the crucial organ where such basal division of memory CD8
      cells occurs. BM memory CD8 cells contain a higher percentage of proliferating
      cells than their corresponding cells in either spleen or lymph nodes from C57BL/6
      mice. This occurs both in the case of memory-phenotype CD44(high) CD8 cells and
      in the case of Ag-specific memory CD8 cells. Importantly, the absolute number of
      Ag-specific memory CD8 cells dividing in the BM largely exceeds that in spleen,
      lymph nodes, liver, and lung taken together. In the BM, Ag-specific memory CD8
      cells express lower levels of CD127, i.e., the alpha-chain of IL-7R, than in
      either spleen or lymph nodes. We interpret these results as indirect evidence
      that Ag-specific memory CD8 cells receive proliferative signals by IL-7 and/or IL
      15 in the BM and propose that the BM acts as a saturable "niche" for the Ag
      independent proliferation of memory CD8 cells. Taken together, our novel findings
      indicate that the BM plays a relevant role in the maintenance of cytotoxic T cell
      memory, in addition to its previously described involvement in long-term Ab
      responses.

PMID- 15944267
TI  - Human mast cells express corticotropin-releasing hormone (CRH) receptors and CRH
      leads to selective secretion of vascular endothelial growth factor.
AB  - Mast cells are critical for allergic reactions, but also for innate or acquired
      immunity and inflammatory conditions that worsen by stress. Corticotropin
      releasing hormone (CRH), which activates the hypothalamic-pituitary-adrenal axis
      under stress, also has proinflammatory peripheral effects possibly through mast
      cells. We investigated the expression of CRH receptors and the effects of CRH in
      the human leukemic mast cell (HMC-1) line and human umbilical cord blood-derived
      mast cells. We detected mRNA for CRH-R1alpha, 1beta, 1c, 1e, 1f isoforms, as well
      as CRH-R1 protein in both cell types. CRH-R2alpha (but not R2beta or R2gamma)
      mRNA and protein were present only in human cord blood-derived mast cells. CRH
      increased cAMP and induced secretion of vascular endothelial growth factor (VEGF)
      without tryptase, histamine, IL-6, IL-8, or TNF-alpha release. The effects were
      blocked by the CRH-R1 antagonist antalarmin, but not the CRH-R2 antagonist
      astressin 2B. CRH-stimulated VEGF production was mediated through activation of
      adenylate cyclase and increased cAMP, as evidenced by the fact that the effect of
      CRH was mimicked by the direct adenylate cyclase activator forskolin and the cell
      permeable cAMP analog 8-bromo-cAMP, whereas it was abolished by the adenylate
      cyclase inhibitor SQ22536. This is the first evidence that mast cells express
      functional CRH receptors and that CRH can induce VEGF secretion selectively. CRH
      induced mast cell-derived VEGF could, therefore, be involved in chronic
      inflammatory conditions associated with increased VEGF, such as arthritis or
      psoriasis, both of which worsen by stress.

PMID- 15944268
TI  - Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the
      generation of HIV-1 Gag-specific Th1 and CD8+ T cell responses.
AB  - One strategy to induce optimal cellular and humoral immune responses following
      immunization is to use vaccines or adjuvants that target dendritic cells and B
      cells. Activation of both cell types can be achieved using specific TLR ligands
      or agonists directed against their cognate receptor. In this study, we compared
      the ability of the TLR7/8 agonist R-848, which signals only via TLR7 in mice,
      with CpG oligodeoxynucleotides for their capacity to induce HIV-1 Gag-specific T
      cell and Ab responses when used as vaccine adjuvants with HIV-1 Gag protein in
      mice. Injection of R-848 and CpG oligodeoxynucleotides alone enhanced the innate
      immune responses in vivo as demonstrated by high serum levels of inflammatory
      cytokines, including IL-12p70 and IFN-alpha, and increased expression of CD80,
      CD86, and CD40 on CD11c(+) dendritic cells. By contrast, R-848 was a relatively
      poor adjuvant for inducing primary Th1 or CD8(+) T cell responses when
      administered with HIV-1 Gag protein. However, when a TLR7/8 agonist structurally
      and functionally similar to R-848 was conjugated to HIV-1 Gag protein both Th1
      and CD8(+) T cells responses were elicited as determined by intracellular
      cytokine and tetramer staining. Moreover, within the population of HIV-1 Gag
      specific CD8(+) CD62(low) cells, approximately 50% of cells expressed CD127, a
      marker shown to correlate with the capacity to develop into long-term memory
      cells. Overall, these data provide evidence that TLR7/8 agonists can be effective
      vaccine adjuvants for eliciting strong primary immune responses with a viral
      protein in vivo, provided vaccine delivery is optimized.

PMID- 15944269
TI  - Positive and negative regulation of the IL-27 receptor during lymphoid cell
      activation.
AB  - Previous reports have focused on the ability of IL-27 to promote naive T cell
      responses but the present study reveals that surface expression of WSX-1, the
      ligand-specific component of the IL-27R, is low on these cells and that highest
      levels are found on effector and memory CD4(+) and CD8(+) T cells. Accordingly,
      during infection with Toxoplasma gondii, in vivo T cell activation is associated
      with enhanced expression of WSX-1, and, in vitro, TCR ligation can induce
      expression of WSX-1 regardless of the polarizing (Th1/Th2) environment present at
      the time of priming. However, while these data establish that mitogenic
      stimulation promotes expression of WSX-1 by T cells, activation of NK cells and
      NKT cells prompts a reduction in WSX-1 levels during acute toxoplasmosis.
      Together, with the finding that IL-2 can suppress expression of WSX-1 by
      activated CD4(+) T cells, these studies indicate that surface levels of the IL
      27R can be regulated by positive and negative signals associated with lymphoid
      cell activation. Additionally, since high levels of WSX-1 are evident on resting
      NK cells, resting NKT cells, effector T cells, regulatory T cells, and memory T
      cells, the current work demonstrates that IL-27 can influence multiple effector
      cells of innate and adaptive immunity.

PMID- 15944270
TI  - Genetic determination of T cell help in loss of tolerance to nuclear antigens.
AB  - Sle1 is a major lupus susceptibility locus in NZM2410 lupus model that is
      associated with a loss of tolerance to nuclear Ags. At least three genes, Sle1a,
      Sle1b, and Sle1c contribute to Sle1, and their relative role in lupus
      pathogenesis is unknown. We show here that Sle1-expressing CD4(+) T cells present
      an activated phenotype associated with increased proliferation and cytokine
      production. In addition, Sle1 CD4(+) T cells provide help to anti-chromatin B
      cells to produce anti-nuclear antibodies, whether or not these B cells express
      Sle1. The Sle1a locus alone accounts for all these Sle1 phenotypes, implying that
      a specific genetic defect in Sle1a is necessary and sufficient to produce
      autoreactive T cells. However, Sle1c induces intermediate T cell activation and
      only provides help to Sle1-expressing anti-chromatin-producing B cells,
      demonstrating the synergic interactions between Sle1c T and Sle1 B cells.
      Moreover, Sle1a and Sle1c were associated with a significantly reduced level of
      CD4(+)CD25(+) regulatory T cells that precedes autoantibody production,
      suggesting a causal relationship with the generation of autoreactive T cells. Our
      study identifies for the first time that a specific genetic defect is responsible
      for lupus pathogenesis by inducing autoreactive T cells to break self-tolerance
      and that this genetic defect is also associated with a decreased number of
      regulatory T cells.

PMID- 15944271
TI  - A role for c-fos/activator protein 1 in B lymphocyte terminal differentiation.
AB  - Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription
      factor is essential for promoting B cell differentiation into plasma cells.
      However, a critical transcription factor for Blimp-1 expression in activated B
      cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L)
      and IL-4, terminal differentiation was induced in the B cells from c-fos
      transgenic (H2-c-fos) mice but barely in those from control littermates and from
      c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in
      the control B cells, and overexpression of c-Fos induced a sufficient amount of
      Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c
      fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1
      for terminal differentiation was induced in those B cells. However, expression of
      c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of
      normal B cells stimulated with CD40L and IL-4. EMSA and chromatin
      immunoprecipitation assays using the AP-1-binding DNA sequence in the murine
      Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear
      protein of LPS-stimulated normal B cells was prolonged more than that in normal B
      cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138(+) B
      cells within germinal center B cells in the spleen and the number of Ab-forming
      cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12
      days after immunization. Thus, although c-Fos is not essential for Blimp-1
      expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal
      differentiation of activated B cells.

PMID- 15944272
TI  - Mouse endothelial cells cross-present lymphocyte-derived antigen on class I MHC
      via a TAP1- and proteasome-dependent pathway.
AB  - In vivo studies suggest that vascular endothelial cells (ECs) can acquire and
      cross-present exogenous Ag on MHC-I but the cellular mechanisms underlying this
      observation remain unknown. We tested whether primary female mouse aortic ECs
      could cross-present exogenous male Ag to the T cell hybridoma, MHH, specific for
      HYUty plus D(b). MHC-I-deficient male spleen cells provided a source of male Ag
      that could not directly stimulate the MHH cells. Addition of male but not female
      MHC-I-deficient spleen cells to wild-type syngeneic female EC induced MHH
      stimulation, demonstrating EC cross-presentation. Lactacystin treatment of the
      donor male MHC-I-deficient spleen cells, to inhibit proteasome function, markedly
      enhanced EC cross-presentation showing that the process is most efficient for
      intact proteins rather than degraded peptide fragments. Additional experiments
      revealed that this EC Ag-processing pathway is both proteasome and TAP1
      dependent. These studies demonstrate that cultured murine aortic ECs can process
      and present MHC-I-restricted Ag derived from a separate, live cell, and they
      offer insight into the molecular requirements involved in this EC Ag presentation
      process. Through this pathway, ECs expressing cross-presented peptides can
      participate in the effector phase of T cell-mediated inflammatory responses such
      as autoimmunity, anti-tumor immunity, and transplant rejection.

PMID- 15944273
TI  - IgE generation and mast cell effector function in mice deficient in IL-4 and IL
      13.
AB  - IL-4 and IL-13 are potent cytokines that drive production of IgE, which is
      critical to the development of atopic disease. In this study, we directly
      compared IgE generation and IgE-dependent mast cell effector function in mouse
      strains lacking IL-4, IL-13, IL-4 + IL-13, or their common receptor component, IL
      4Ralpha. Although serum IgE was undetectable under resting conditions in most
      animals deficient in one or both cytokines, peritoneal mast cells from mice
      lacking IL-4 or IL-13 had only partial reductions in surface IgE level. In
      contrast, peritoneal mast cells from IL-4/13(-/-) and IL-4Ralpha(-/-) animals
      were severely deficient in surface IgE, and showed no detectable degranulation
      following treatment with anti-IgE in vitro. Surprisingly, however, intradermal
      challenge with high concentrations of anti-IgE Ab induced an ear-swelling
      response in these strains, implying some capacity for IgE-mediated effector
      function in tissue mast cells. Furthermore, upon specific immunization with OVA,
      both IL-4/IL-13(-/-) and IL-4Ralpha(-/-) mice produced detectable levels of serum
      IgE and Ag-specific IgG1, and generated strong ear-swelling responses to
      intradermal administration of anti-IgE. These findings suggest that a mechanism
      for IgE production exists in vivo that is independent of IL-4 or IL-13.

PMID- 15944274
TI  - Augmentation of cutaneous immune responses by ATP gamma S: purinergic agonists
      define a novel class of immunologic adjuvants.
AB  - Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein
      coupled P2YRs. In this study we report that intradermal administration of
      ATPgammaS, a hydrolysis-resistant P2 agonist, results in an enhanced contact
      hypersensitivity response in mice. Furthermore, ATPgammaS enhanced the induction
      of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced
      the Ag-presenting function of Langerhans cells (LCs) in vitro. Exposure of a LC
      like cell line to ATPgammaS in the presence of LPS and GM-CSF augmented the
      induction of I-A, CD80, CD86, IL-1beta, and IL-12 p40 while inhibiting the
      expression of IL-10, suggesting that the immunostimulatory activities of
      purinergic agonists in the skin are mediated at least in part by P2Rs on APCs. In
      this regard, an LC-like cell line was found to express mRNA for P2X(1), P2X(7),
      P2Y(1), P2Y(2), P2Y(4), P2Y(9), and P2Y(11) receptors. We suggest that ATP, when
      released after trauma or infection, may act as an endogenous adjuvant to enhance
      the immune response, and that P2 agonists may augment the efficacy of vaccines.

PMID- 15944275
TI  - The functional heterogeneity of type 1 effector T cells in response to infection
      is related to the potential for IFN-gamma production.
AB  - The expression of IFN-gamma is a hallmark of Th1 cells and CD8(+) effector T
      cells and is the signature cytokine of type 1 responses. However, it is not known
      whether T cells are homogeneous in their capacity to produce IFN-gamma, whether
      this potential varies between tissues, and how it relates to the production of
      other effector molecules. In the present study we used bicistronic IFN-gamma
      enhanced yellow fluorescent protein (IFN-gamma-eYFP) reporter mice (Yeti) and MHC
      class I tetramers to directly quantify IFN-gamma expression at the single cell
      level. The eYFP fluorescence of Th1 cells and CD8(+) effector T cells was broadly
      heterogeneous even before cell division and correlated with both the abundance of
      IFN-gamma transcripts and the secretion of IFN-gamma upon stimulation. CD4(+) and
      CD8(+) T cells of influenza-infected mice revealed a similarly heterogeneous IFN
      gamma expression, and eYFP(high) cells were only found in the infected lung. Ag
      specific T cells were in all examined tissues eYFP(+), but also heterogeneous in
      their reporter fluorescence, and eYFP(high) cells were also restricted to the
      infected lung. A similar heterogeneity was observed in Toxoplasma gondii-infected
      animals, but eYFP(high) cells were restricted to different tissues. Highly eYFP
      fluorescent cells produced elevated levels of proinflammatory cytokines and
      chemokines in addition to IFN-gamma, suggesting their coregulated expression as a
      functional unit in highly differentiated effector T cells.

PMID- 15944276
TI  - Iodine and IFN-gamma synergistically enhance intercellular adhesion molecule 1
      expression on NOD.H2h4 mouse thyrocytes.
AB  - NOD.H2(h4) mice spontaneously develop autoimmune lymphocytic thyroiditis that
      mimics human Hashimoto's thyroiditis, a disease where iodine, IFN-gamma, and
      adhesion molecules have all been implicated in the pathogenesis. To study how
      iodine and IFN-gamma modulate the expression of ICAM-1, we analyzed NOD.H2(h4)
      thyrocytes in baseline conditions (day 0) and at several time points following
      supplementation of iodine in the drinking water. On day 0, a small percentage (
      approximately 10%) of thyrocytes constitutively expressed ICAM-1. The expression
      gradually increased to 13, 25, and 41% on days 7, 14 and 28, respectively,
      returning to baseline (9%) on day 35. The initial ICAM-1 kinetics was paralleled
      by thyroidal infiltration of CD45(+) hemopoietic cells, which increased from an
      average of 4% on day 0 to an average of 13, 21, and 24% on days 14, 28, and 35,
      respectively. To distinguish whether the observed ICAM-1 increase was a direct
      effect of iodine or a consequence of the immune infiltrate, we treated mouse
      primary thyrocyte cultures with 0.01 mM sodium iodine and showed a 3-fold
      increased ICAM-1 expression. To assess interaction between IFN-gamma and iodine,
      we analyzed CD45 and ICAM-1expression on thyrocytes from NOD.H2(h4) wild-type and
      NOD.H2(h4) thyr-IFN-gamma transgenic littermates. Strikingly, IFN-gamma
      interacted synergistically with iodine to enhance ICAM-1 expression on
      thyrocytes. These findings suggest that iodine and IFN-gamma cooperate to promote
      thyroidal expression of ICAM-1 in this mouse model of thyroiditis, highlighting
      the complex interplay present in the pathogenesis of Hashimoto's thyroiditis.

PMID- 15944277
TI  - An MHC class Ib-restricted TCR that cross-reacts with an MHC class Ia molecule.
AB  - TCR transgenic 6C5 T cells recognize an insulin B chain epitope presented by the
      nonclassical class I MHC molecule, Qa-1(b). Positive selection of these T cells
      was shown previously to require Qa-1(b). Despite dedicated specificity for Qa
      1(b), evidence presented in the current study indicates that 6C5 T cells can
      cross-recognize a classical class I molecule. Clonal deletion was observed
      unexpectedly in 6C5.H-2(bxq) mice, which do not express I-E MHC class II
      molecules and thus should not be subject to superantigen-mediated negative
      selection. 6C5 T cells were observed to respond in vivo and in vitro to spleen
      cells from allogeneic H-2(q) mice, and specificity was mapped to D(q). Evidence
      was obtained for direct recognition of D(q), rather than indirect presentation of
      a D(q)-derived peptide presented by Qa-1(b). Polyclonal CD8(+) T cells from class
      Ia-deficient K(b)D(b-/-) mice reacted in vitro to allogeneic spleen cells with an
      apparent frequency comparable to conventional class Ia-restricted T cells. Our
      results provide a clear example of a Qa-1-specific TCR that can cross-react with
      a class Ia molecule and evidence supporting the idea that this may be a common
      property of T cells selected by class Ib molecules.

PMID- 15944278
TI  - Restricted STAT5 activation dictates appropriate thymic B versus T cell lineage
      commitment.
AB  - The molecular mechanisms regulating lymphocyte lineage commitment remain poorly
      characterized. To explore the role of the IL7R in this process, we generated
      transgenic mice that express a constitutively active form of STAT5 (STAT5b-CA), a
      key downstream IL7R effector, throughout lymphocyte development. STAT5b-CA mice
      exhibit a 40-fold increase in pro-B cells in the thymus. As documented by BrdU
      labeling studies, this increase is not due to enhanced B cell proliferation.
      Thymic pro-B cells in STAT5b-CA mice show a modest increase in cell survival (
      approximately 4-fold), which correlates with bcl-x(L) expression. However, bcl
      x(L) transgenic mice do not show increases in thymic B cell numbers. Thus, STAT5
      dependent bcl-x(L) up-regulation and enhanced B cell survival are not sufficient
      to drive the thymic B cell development observed in STAT5b-CA mice. Importantly,
      thymic pro-B cells in STAT5b-CA mice are derived from early T cell progenitors
      (ETPs), suggesting that STAT5 acts by altering ETP lineage commitment. Supporting
      this hypothesis, STAT5 binds to the pax5 promoter in ETPs from STAT5b-CA mice and
      induces pax5, a master regulator of B cell development. Conversely, STAT5b-CA
      mice exhibit a decrease in the DN1b subset of ETPs, demonstrating that STAT5
      activation inhibits early T cell differentiation or lineage commitment. On the
      basis of these findings, we propose that the observed expression of the IL-7R on
      common lymphoid progenitors, but not ETPs, results in differential STAT5
      signaling within these distinct progenitor populations and thus helps ensure
      appropriate development of B cells and T cells in the bone marrow and thymic
      environments, respectively.

PMID- 15944279
TI  - Recombinant tumor-associated MUC1 glycoprotein impairs the differentiation and
      function of dendritic cells.
AB  - Tumors exploit several strategies to evade immune recognition, including the
      production of a large number of immunosuppressive factors, which leads to reduced
      numbers and impaired functions of dendritic cells (DCs) in the vicinity of
      tumors. We have investigated whether a mucin released by tumor cells could be
      involved in causing these immunomodulating effects on DCs. We used a recombinant
      purified form of the MUC1 glycoprotein, an epithelial associated mucin that is
      overexpressed, aberrantly glycosylated, and shed during cancer transformation.
      The O-glycosylation profile of the recombinant MUC1 glycoprotein (ST-MUC1)
      resembled that expressed by epithelial tumors in vivo, consisting of large
      numbers of sialylated core 1 (sialyl-T, ST) oligosaccharides. When cultured in
      the presence of ST-MUC1, human monocyte-derived DCs displayed a modified
      phenotype with decreased expression of costimulatory molecules (CD86, CD40), Ag
      presenting molecules (DR and CD1d), and differentiation markers (CD83). In
      contrast, markers associated with an immature phenotype, CD1a and CD206 (mannose
      receptor), were increased. This effect was already evident at day 4 of DC culture
      and was dose dependent. The modified phenotype of DCs corresponded to an altered
      balance in IL-12/IL-10 cytokine production, with DC expressing an IL-10(high)IL
      12(low) phenotype after exposure to ST-MUC1. These DCs were defective in their
      ability to induce immune responses in both allogeneic and autologous settings, as
      detected in proliferation and ELISPOT assays. The altered DC differentiation and
      Ag presentation function induced by the soluble sialylated tumor-associated mucin
      may represent a mechanism by which epithelial tumors can escape
      immunosurveillance.

PMID- 15944280
TI  - Development of the expressed Ig CDR-H3 repertoire is marked by focusing of
      constraints in length, amino acid use, and charge that are first established in
      early B cell progenitors.
AB  - To gain insight into the mechanisms that regulate the development of the H chain
      CDR3 (CDR-H3), we used the scheme of Hardy to sort mouse bone marrow B lineage
      cells into progenitor, immature, and mature B cell fractions, and then performed
      sequence analysis on V(H)7183-containing Cmu transcripts. The essential
      architecture of the CDR-H3 repertoire observed in the mature B cell fraction F
      was already established in the early pre-B cell fraction C. These architectural
      features include V(H) gene segment use preference, D(H) family usage, J(H) rank
      order, predicted structures of the CDR-H3 base and loop, and the amino acid
      composition and average hydrophobicity of the CDR-H3 loop. With development, the
      repertoire was focused by eliminating outliers to what appears to be a preferred
      repertoire in terms of length, amino acid composition, and average
      hydrophobicity. Unlike humans, the average length of CDR-H3 increased during
      development. The majority of this increase came from enhanced preservation of
      J(H) sequence. This was associated with an increase in the prevalence of
      tyrosine. With an accompanying increase in glycine, a shift in hydrophobicity was
      observed in the CDR-H3 loop from near neutral in fraction C (-0.08 +/- 0.03) to
      mild hydrophilic in fraction F (-0.17 +/- 0.02). Fundamental constraints on the
      sequence and structure of CDR-H3 are thus established before surface IgM
      expression.

PMID- 15944281
TI  - DNA polymerase eta contributes to strand bias of mutations of A versus T in
      immunoglobulin genes.
AB  - DNA polymerase (pol) eta participates in hypermutation of A:T bases in Ig genes
      because humans deficient for the polymerase have fewer substitutions of these
      bases. To determine whether polymerase eta is also responsible for the well-known
      preference for mutations of A vs T on the nontranscribed strand, we sequenced
      variable regions from three patients with xeroderma pigmentosum variant (XP-V)
      disease, who lack polymerase eta. The frequency of mutations in the intronic
      region downstream of rearranged J(H)4 gene segments was similar between XP-V and
      control clones; however, there were fewer mutations of A:T bases and
      correspondingly more substitutions of C:G bases in the XP-V clones (p < 10(-7)).
      There was significantly less of a bias for mutations of A compared with T
      nucleotides in the XP-V clones compared with control clones, whereas the
      frequencies for mutations of C and G were identical in both groups. An analysis
      of mutations in the WA sequence motif suggests that polymerase eta generates more
      mutations of A than T on the nontranscribed strand. This in vivo data from
      polymerase eta-deficient B cells correlates well with the in vitro specificity of
      the enzyme. Because polymerase eta inserts more mutations opposite template T
      than template A, it would generate more substitutions of A on the newly
      synthesized strand.

PMID- 15944282
TI  - Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from
      cells expressing activation-induced cytidine deaminase.
AB  - Activation-induced cytidine deaminase (AID) is required for somatic hypermutation
      and class switch recombination of Ig genes in B cells. Although AID has been
      shown to deaminate deoxycytidine to deoxyuridine in DNA in vitro, there is no
      physical evidence for increased uracils in DNA from cells expressing AID in vivo.
      We used several techniques to detect uracil bases in a gene that was actively
      transcribed in Escherichia coli cells expressing AID. Plasmid DNA containing the
      gene was digested with uracil-DNA glycosylase to remove uracil, and
      apurinic/apryimidinic endonuclease to nick the abasic site. The nicked DNA was
      first analyzed using alkaline gel electrophoresis, in which there was a 2-fold
      increase in the linear form of the plasmid after AID induction compared with
      plasmid from noninduced bacteria. Second, using a quantitative denaturing
      Southern blot technique, the gene was predominantly nicked in the nontranscribed
      strand compared with the transcribed strand. Third, using ligation-mediated PCR,
      the nicks were mapped on the nontranscribed strand and were located primarily at
      cytosine bases. These data present direct evidence for the presence of uracils in
      DNA from cells that are induced to express AID, and they are preferentially
      generated at cytosines in the nontranscribed strand during transcription.

PMID- 15944283
TI  - The influences of hinge length and composition on the susceptibility of human IgA
      to cleavage by diverse bacterial IgA1 proteases.
AB  - The influences of IgA hinge length and composition on its susceptibility to
      cleavage by bacterial IgA1 proteases were examined using a panel of IgA hinge
      mutants. The IgA1 proteases of Streptococcus pneumoniae, Streptococcus sanguis
      strains SK4 and SK49, Neisseria meningitidis, Neisseria gonorrhoeae, and
      Haemophilus influenzae cleaved IgA2-IgA1 half hinge, an Ab featuring half of the
      IgA1 hinge incorporated into the equivalent site in IgA1 protease-resistant IgA2,
      whereas those of Streptococcus mitis, Streptococcus oralis, and S. sanguis strain
      SK1 did not. Hinge length reduction by removal of two of the four C-terminal
      proline residues rendered IgA2-IgA1 half hinge resistant to all streptococcal
      IgA1 metalloproteinases but it remained sensitive to cleavage by the serine-type
      IgA1 proteases of Neisseria and Haemophilus spp. The four C-terminal proline
      residues could be substituted by alanine residues or transferred to the N
      terminal extremity of the hinge without affect on the susceptibility of the Ab to
      cleavage by serine-type IgA1 proteases. However, their removal rendered the Ab
      resistant to cleavage by all the IgA1 proteases. We conclude that the serine-type
      IgA1 proteases of Neisseria and Haemophilus require the Fab and Fc regions to be
      separated by at least ten (or in the case of N. gonorrhoeae type I protease,
      nine) amino acids between Val(222) and Cys(241) (IgA1 numbering) for efficient
      access and cleavage. By contrast, the streptococcal IgA1 metalloproteinases
      require 12 or more appropriate amino acids between the Fab and Fc to maintain a
      minimum critical distance between the scissile bond and the start of the Fc.

PMID- 15944284
TI  - Transcriptional regulation of the mouse IL-7 receptor alpha promoter by
      glucocorticoid receptor.
AB  - Expression of the IL-7R alpha-chain (IL-7Ralpha) is strictly regulated during the
      development and maturation of lymphocytes. Glucocorticoids (GC) have pleiotypic
      effects on the growth and function of lymphocytes. Although GC have been reported
      to induce the transcription of IL-7Ralpha gene in human T cells, its molecular
      mechanism is largely unknown. In this study, we show that GC up-regulate the
      levels of IL-7Ralpha mRNA and protein in mouse T cells. This effect does not
      require protein synthesis de novo, because protein synthesis inhibitors do not
      block the process. Mouse IL-7Ralpha promoter has striking homology with human and
      rat, containing consensus motifs of Ikaros, PU.1, and Runx1 transcription
      factors. In addition, a conserved noncoding sequence (CNS) of approximately 270
      bp was found 3.6-kb upstream of the promoter, which was designated as CNS-1. A GC
      receptor (GR) motif is present in the CNS-1 region. Importantly, we show by
      reporter assay that the IL-7Ralpha promoter has specific transcription activity
      in T cells. This activity highly depends on the PU.1 motif. Furthermore, GC
      treatment augments the transcriptional activity through the GR motif in the CNS-1
      region. We also demonstrate that GR binds to the GR motif by EMSA. In addition,
      by chromatin immunoprecipitation assay, we show that GR is rapidly recruited to
      endogenous CNS-1 chromatin after GC stimulation. These results demonstrate that
      GR binds to the GR motif in the CNS-1 region after GC stimulation and then
      activates the transcription of the IL-7Ralpha promoter. Thus, this study
      identifies the IL-7Ralpha CNS-1 region as a GC-responsive element.

PMID- 15944285
TI  - Differential Src family kinase activity requirements for CD3 zeta
      phosphorylation/ZAP70 recruitment and CD3 epsilon phosphorylation.
AB  - The current model of T cell activation is that TCR engagement stimulates Src
      family tyrosine kinases (SFK) to phosphorylate CD3zeta. CD3zeta phosphorylation
      allows for the recruitment of the tyrosine kinase ZAP70, which is phosphorylated
      and activated by SFK, leading to the phosphorylation of downstream targets. We
      stimulated mouse CTLs with plate-bound anti-CD3 and, after cell lysis, recovered
      proteins that associated with the CD3 complex. The protein complexes were not
      preformed, and a number of tyrosine-phosphorylated proteins were inducibly and
      specifically associated with the TCR/CD3 complex. These results suggest that
      complex formation only occurs at the site of TCR engagement. The recruitment and
      tyrosine phosphorylation of most proteins were abolished when T cells were
      stimulated in the presence of the SFK inhibitor PP2. Surprisingly, CD3zeta, but
      not CD3epsilon, was inducibly tyrosine phosphorylated in the presence of PP2.
      Furthermore, ZAP70 was recruited, but not phosphorylated, after TCR stimulation
      in the presence of PP2, thus confirming the phosphorylation status of CD3zeta.
      These data suggest that there is a differential requirement for SFK activity in
      phosphorylation of CD3zeta vs CD3epsilon. Consistent with this possibility, ZAP70
      recruitment was also detected with anti-CD3-stimulated, Lck-deficient human
      Jurkat T cells. We conclude that TCR/CD3-induced CD3zeta phosphorylation and
      ZAP70 recruitment do not absolutely require Lck or other PP2-inhibitable SFK
      activity, but that SFK activity is absolutely required for CD3epsilon and ZAP70
      phosphorylation. These data reveal the potential for regulation of signaling
      through the TCR complex by the differential recruitment or activation of SFK.

PMID- 15944286
TI  - Differential expression regulation of the alpha and beta subunits of the PA28
      proteasome activator in mature dendritic cells.
AB  - Activation of dendritic cells (DC) by Th-dependent (CD40) or -independent (LPS,
      CpG, or immune complexes) agonistic stimuli strongly enhances the expression of
      the proteasome activator PA28alphabeta complex. Upon activation of DC, increased
      MHC class I presentation occurred of the melanocyte-associated epitope tyrosinase
      related protein 2(180-188) in a PA28alphabeta-dependent manner. In contrast to
      other cell types, regulation of PA28alphabeta expression in DC after maturation
      was found to be IFN-gamma independent. In the present study, we show that
      expression of PA28alpha and beta subunits was differentially regulated. Firstly,
      PA28alpha expression is high in both immature and mature DC. In contrast,
      PA28beta expression is low in immature DC and strongly increased in mature DC.
      Secondly, we show the presence of a functional NF-kappaB site in the PA28beta
      promoter, which is absent in the PA28alpha promoter, indicating regulation of
      PA28beta expression by transcription factors of the NF-kappaB family. In
      addition, glycerol gradient analysis of DC lysates revealed elevated
      PA28alphabeta complex formation upon maturation. Thus, induction of PA28beta
      expression allows proper PA28alphabeta complex formation, thereby enhancing
      proteasome activity in activated DC. Therefore, maturation of DC not only
      improves costimulation but also MHC class I processing. This mechanism enhances
      the CD8(+) CTL (cross)-priming capacity of mature DC.

PMID- 15944287
TI  - STAT-1 mediates the stimulatory effect of IL-10 on CD14 expression in human
      monocytic cells.
AB  - IL-10, an anti-inflammatory cytokine, has been shown to exhibit stimulatory
      functions including CD14 up-regulation on human monocytic cells. CD14-mediated
      signaling following LPS stimulation of monocytic cells results in the synthesis
      of proinflammatory cytokines. Our results show that LPS-induced CD14 expression
      on monocytic cells may be mediated by endogenously produced IL-10. To investigate
      the molecular mechanism by which IL-10 enhances CD14 expression, both human
      monocytes and the promyelocytic HL-60 cells were used as model systems. IL-10
      induced the phosphorylation of PI3K and p42/44 ERK MAPK. By using specific
      inhibitors for PI3K (LY294002) and ERK MAPKs (PD98059), we demonstrate that
      LY294002 either alone or in conjunction with PD98059 inhibited IL-10-induced
      phosphorylation of STAT-1 and consequently CD14 expression. However, IL-10
      induced STAT-3 phosphorylation remained unaffected under these conditions.
      Finally, STAT-1 interfering RNA inhibited IL-10-induced CD14 expression. Taken
      together, these results suggest that IL-10-induced CD14 up-regulation in human
      monocytic cells may be mediated by STAT-1 activation through the activation of
      PI3K either alone or in concert with the ERK MAPK.

PMID- 15944288
TI  - Qualitative and quantitative differences in peptides bound to HLA-B27 in the
      presence of mouse versus human tapasin define a role for tapasin as a size
      dependent peptide editor.
AB  - Tapasin (Tpn) is a chaperone of the endoplasmic reticulum involved in peptide
      loading to MHC class I proteins. The influence of mouse Tpn (mTpn) on the HLA
      B*2705-bound peptide repertoire was analyzed to characterize the species
      specificity of this chaperone. B*2705 was expressed on Tpn-deficient human
      721.220 cells cotransfected with human (hTpn) or mTpn. The heterodimer to beta(2)
      microglobulin-free H chain ratio on the cell surface was reduced with mTpn,
      suggesting lower B*2705 stability. The B*2705-bound peptide repertoires loaded
      with hTpn or mTpn shared 94-97% identity, although significant differences in
      peptide amount were observed in 16-17% of the shared ligands. About 3-6% of
      peptides were bound only with either hTpn or mTpn. Nonamers differentially bound
      with mTpn had less suitable anchor residues and bound B*2705 less efficiently in
      vitro than those loaded only with hTpn or shared nonamers. Decamers showed a
      different pattern: those found only with mTpn had similarly suitable residues as
      shared decamers and bound B*2705 with high efficiency. Peptides differentially
      presented by B*2705 on human or mouse cells showed an analogous pattern of
      residue suitability, suggesting that the effect of mTpn on B*2705 loading is
      comparable in both cell types. Thus, mTpn has quantitative and qualitative
      effects on the B*2705-bound peptide repertoire, impairing presentation of some
      suitable ligands and allowing others with suboptimal anchor residues and lower
      affinity to be presented. Our results favor a size-dependent peptide editing role
      of Tpn for HLA-B*2705 that is species-dependent and suboptimally performed, at
      least for nonamers, by mTpn.

PMID- 15944289
TI  - Sustained pre-TCR expression in Notch1IC-transgenic rats impairs T cell
      maturation and selection.
AB  - Notch1 is involved in directing cell fate decisions in a variety of developmental
      scenarios. Extending previous experiments in mice, we generated transgenic rats
      expressing the intracellular domain of Notch1 in the thymus. Importantly, this
      leads to sustained expression of the pre-TCR throughout thymocyte development,
      accompanied by a reduction of alphabetaTCR complexes. In addition, re-expression
      of RAG-1 and RAG-2 in TCRbeta(+) cells is impaired, and the Valpha repertoire is
      altered. Consequently, thymocytes in transgenic rats do not undergo positive
      selection and largely fail to progress to the single positive stage. According to
      our model, the previously reported effects of Notch1 on the CD4/CD8 cell fate
      decision may be explained by a differential sensitivity of the two lineages
      toward altered TCR signaling.

PMID- 15944290
TI  - T cell retargeting with MHC class I-restricted antibodies: the CD28 costimulatory
      domain enhances antigen-specific cytotoxicity and cytokine production.
AB  - T cells require both primary and costimulatory signals for optimal activation.
      The primary Ag-specific signal is delivered by engagement of the TCR. The second
      Ag-independent costimulatory signal is mediated by engagement of the T cell
      surface costimulatory molecule CD28 with its target cell ligand B7. However, many
      tumor cells do not express these costimulatory molecules. We previously
      constructed phage display derived F(AB), G8, and Hyb3, Ab-based receptors with
      identical specificity but distinct affinities for HLA-A1/MAGE-A1, i.e., "TCR
      like" specificity. These chimeric receptors comprised the FcepsilonRI-gamma
      signaling element. We analyzed whether linking the CD28 costimulation structure
      to it (gamma + CD28) could affect the levels of MHC-restricted cytolysis and/or
      cytokine production. Human scFv-G8(POS) T lymphocytes comprising the gamma + CD28
      vs the gamma signaling element alone produced substantially more IL-2, TNF-alpha,
      and IFN-gamma in response to HLA-A1/MAGE-A1(POS) melanoma cells. Also a drastic
      increase in cytolytic capacity of scFv-G8(POS) T cells, equipped with gamma +
      CD28 vs the gamma-chain alone was observed.

PMID- 15944291
TI  - Enhanced expression of CD20 in human tumor B cells is controlled through ERK
      dependent mechanisms.
AB  - Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted
      cells. Although the majority of B cell malignancies express the CD20 Ag, only
      approximately 50% of patients will respond to single-agent rituximab. The
      available data suggest that a decreased CD20 expression could account for the
      lack of response observed in some patients treated with rituximab. Despite the
      potential critical role of CD20 in the biology of B cell malignancies, the
      mechanisms controlling its expression are poorly understood. We evaluated the
      effect of the immune modulator agent bryostatin-1 on the expression of CD20 in
      non-Hodgkin's lymphoma cells. Using the B cell lines, DB and RAMOS, as well as
      tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated
      that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The
      enhanced expression of CD20 was associated with increased transcriptional
      activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected.
      The effect of bryostatin-1 on CD20 expression in non-Hodgkin's lymphoma cells was
      mediated through the MAPK kinase/ERK signal transduction pathway and involved
      protein kinase C, but was independent of p38 MAPK and was insensitive to
      dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the
      proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the
      first time that ERK phosphorylation is required for the up-regulated expression
      of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and
      rituximab could be a valuable combined therapy for B cell malignancies.

PMID- 15944292
TI  - Glucocorticoid-induced TNF receptor functions as a costimulatory receptor that
      promotes survival in early phases of T cell activation.
AB  - Glucocorticoid-induced TNFR (GITR) is a member of the TNFR family that can
      inhibit the suppressive function of regulatory T cells and promote the survival
      and activation of T cells. However, little is known about the molecular
      mechanisms regulating T cell survival and activation downstream of GITR. To gain
      further insight into the cellular events and signaling pathways triggered by
      GITR, survival, proliferation, and cytokine production as well as activation of
      MAPKs and NF-kappaB were monitored after cross-linking of the receptor on naive
      and activated T cells. GITR cross-linking provided costimulation of naive and
      activated T cells and resulted in activation of MAPKs and NF-kappaB. Although
      GITR-induced signaling pathways augmented the survival of naive T cells, they
      were not sufficient to inhibit activation-induced cell death triggered by CD3
      cross-linking of activated T cells. Differences in the contributions of GITR to
      cell survival between naive and activated T cells suggest that the receptor
      triggers specific pathways depending on the activation state of the T cell.

PMID- 15944293
TI  - Glucocorticoid-induced TNF receptor, a costimulatory receptor on naive and
      activated T cells, uses TNF receptor-associated factor 2 in a novel fashion as an
      inhibitor of NF-kappa B activation.
AB  - Glucocorticoid-induced TNFR (GITR) has been implicated as an essential regulator
      of immune responses to self tissues and pathogens. We have recently shown that
      GITR-induced cellular events promote survival of naive T cells, but are
      insufficient to protect against activation-induced cell death. However, the
      molecular mechanisms of GITR-induced signal transduction that influence
      physiologic and pathologic immune responses are not well understood. TNFR
      associated factors (TRAFs) are pivotal adapter proteins involved in signal
      transduction pathways of TNFR-related proteins. Yeast two-hybrid assays and
      studies in HEK293 cells and primary lymphocytes indicated interactions between
      TRAF2 and GITR mediated by acidic residues in the cytoplasmic domain of the
      receptor. GITR-induced activation of NF-kappaB is blocked by A20, an NF-kappaB
      inducible protein that interacts with TRAFs and functions in a negative feedback
      mechanism downstream of other TNFRs. Interestingly, in contrast with its effects
      on signaling triggered by other TNFRs, our functional studies revealed that TRAF2
      plays a novel inhibitory role in GITR-triggered NF-kappaB activation.

PMID- 15944294
TI  - Structure/function analysis of tristetraprolin (TTP): p38 stress-activated
      protein kinase and lipopolysaccharide stimulation do not alter TTP function.
AB  - Tristetraprolin (TTP) is the only trans-acting factor shown to be capable of
      regulating AU-rich element-dependent mRNA turnover at the level of the intact
      animal; however, the mechanism by which TTP mediated RNA instability is unknown.
      Using an established model system, we performed structure/function analysis with
      TTP as well as examined the current hypothesis that TTP function is regulated by
      p38-MAPKAP kinase 2 (MK2) activation. Deletion of either the N- or C-terminal
      domains inhibited TTP function. Extensive mutagenesis, up to 16%, of serines and
      threonines, some of which were predicted to mediate proteasomal targeting, did
      not alter human TTP function. Mutation of the conserved MK2 phosphorylation sites
      enhanced human TTP function in both resting and p38-stress-activated protein
      kinase-MK2-activated cells. However, p38-stress-activated protein kinase-MK2
      activation did not alter the activity of either wild-type or mutant TTP. TTP
      localized to the stress granules, with arsenite treatment reducing this
      localization. In contrast, arsenite treatment enhanced stress granule
      localization of the MK2 mutant, consistent with the involvement of additional
      pathways regulating this event. Finally, we determined that, in response to LPS
      stimulation, human TTP moves onto the polysomes, and this movement occurs in the
      absence of 14-3-3. Taken together, these data indicate that, although p38
      activation alters TTP entry into the stress granule, it does not alter TTP
      function. Moreover, the interaction of TTP with 14-3-3, which may limit entry
      into the stress granule, is not involved in the downstream message stabilization
      events.

PMID- 15944295
TI  - The non-MHC quantitative trait locus Cia5 contains three major arthritis genes
      that differentially regulate disease severity, pannus formation, and joint damage
      in collagen- and pristane-induced arthritis.
AB  - Cia5 is a locus on rat chromosome 10 which regulates the severity of collagen-
      and pristane-induced arthritis (CIA and PIA). To refine the region toward
      positional identification, Cia5 subcongenic strains were generated and studied in
      PIA and CIA. The protective effect of the telomeric locus Cia5a was confirmed in
      both models. A second arthritis severity locus (Cia5d) was identified within the
      most centromeric portion of Cia5. DA.F344(Cia5d) rats had a significantly lower
      median arthritis severity index in PIA, but not in CIA, compared with DA. On
      histologic analyses DA.F344(Cia5a) and DA.F344(Cia5d) congenics with PIA
      preserved a nearly normal joint architecture compared with DA, including
      significant reduction in synovial hyperplasia, pannus, angiogenesis, inflammatory
      infiltration, bone and cartilage erosions. Cia5 and Cia5a synovial levels of IL
      1beta mRNA were reduced. Although both DA.F344(Cia5) and DA.F344(Cia5a) rats were
      protected in CIA, the arthritis scores of DA.F344(Cia5) were significantly higher
      than those of DA.F344(Cia5a), suggesting the existence of a third locus where
      F344-derived alleles centromeric from Cia5a contribute to increased arthritis
      severity. The existence of the third locus was further supported by higher levels
      of autoantibodies against rat type II collagen in DA.F344(Cia5) congenics
      compared with DA.F344(Cia5a). Our results determined that Cia5 contains three
      major arthritis severity regulatory loci regulating central events in the
      pathogenesis of arthritis, and differentially influencing CIA and PIA. These loci
      are syntenic to regions on human chromosomes 17q and 5q implicated in the
      susceptibility to rheumatoid arthritis, suggesting that the identification of
      these genes will be relevant to human disease.

PMID- 15944296
TI  - Exacerbated susceptibility to infection-stimulated immunopathology in CD1d
      deficient mice.
AB  - Mice lacking functional CD1d genes were used to study mechanisms of resistance to
      the protozoan parasite Toxoplasma gondii. Wild-type (WT) BALB/c mice, CD1d
      deficient BALB/c mice, and WT C57BL/6 mice all survived an acute oral infection
      with a low dose of mildly virulent strain ME49 T. gondii cysts. In contrast, most
      CD1d-deficient C57BL/6 mice died within 2 wk of infection. Despite having
      parasite burdens that were only slightly higher than WT mice, CD1d-deficient
      C57BL/6 mice displayed greater weight loss and intestinal pathology. In C57BL/6
      mice, CD4(+) cells can cause intestinal pathology during T. gondii infection.
      Compared with WT mice, infected CD1d-deficient C57BL/6 mice had higher
      frequencies and numbers of activated (CD44(high)) CD4(+) cells in mesenteric
      lymph nodes. Depletion of CD4(+) cells from CD1d-deficient mice reduced weight
      loss and prolonged survival, demonstrating a functional role for CD4(+) cells in
      their increased susceptibility to T. gondii infection. CD1d-deficient mice are
      deficient in Valpha14(+) T cells, a major population of NKT cells. Involvement of
      these cells in resistance to T. gondii was investigated using gene-targeted
      Jalpha18-deficient C57BL/6 mice, which are deficient in Valpha14(+) T cells.
      These mice did not succumb to acute infection, but experienced greater weight
      loss and more deaths than B6 mice during chronic infection, indicating that
      Valpha14(+) cells contribute to resistance to T. gondii. The data identify CD4(+)
      cells as a significant component of the marked susceptibility to T. gondii
      infection observed in CD1d-deficient C57BL/6 mice, and establish T. gondii as a
      valuable tool for deciphering CD1d-dependent protective mechanisms.

PMID- 15944297
TI  - B lymphocyte activation by human papillomavirus-like particles directly induces
      Ig class switch recombination via TLR4-MyD88.
AB  - Vaccination with human papillomavirus type 16 (HPV16) L1 virus-like particles
      (VLP) induces both high titer neutralizing IgG and protective immunity. Because
      protection from experimental infection by papillomavirus is mediated by
      neutralizing IgG, we sought the mechanisms that trigger humoral immunity to HPV16
      L1 VLP. We find that HPV16 L1 VLP bind to murine B lymphocytes thereby inducing
      activation-induced cytidine deaminase expression and Ig class switch
      recombination to cause the generation of IgG. HPV16 L1 VLP also activate
      production of proinflammatory factors IFN-alpha, IL-6, MIP-1alpha, RANTES, and
      KC, up-regulate the expression of costimulatory molecules by naive B cells, and
      increase the B1 B cell subpopulation. These B cell responses to HPV16 L1 VLP are
      dependent upon MyD88. Although MyD88(-/-) B cells produce only mu transcript
      after exposure to HPV16 L1 VLP, MyD88(+/+) B cells express alpha, gamma, and mu
      Ig H chain and activation-induced cytidine deaminase transcripts. Notably, TLR4
      mutant C3H/HeJ mice exhibited significantly reduced HPV16 VLP-specific IgG1,
      IgG2a, IgG2b, and IgG3 titers after vaccination as compared with the control
      C3H/HeOuJ mice. HPV16 L1 VLP directly activated class switch recombination and
      costimulatory molecule expression by B cells of C3H/HeOuJ mice but not C3H/HeJ
      mice. Thus HPV16 L1 VLP directly activate B cells to induce CD4(+) T cell
      independent humoral immune responses via TLR4- and MyD88-dependent signaling.

PMID- 15944298
TI  - Generation of antifungal effector CD8+ T cells in the absence of CD4+ T cells
      during Cryptococcus neoformans infection.
AB  - Immunity to the opportunistic fungus Cryptococcus neoformans is dependent on cell
      mediated immunity. Individuals with defects in cellular immunity, CD4(+) T cells
      in particular, are susceptible to infection with this pathogen. In host defense
      against a number of pathogens, CD8(+) T cell responses are dependent upon CD4(+)
      T cell help. The goal of these studies was to determine whether CD4(+) T cells
      are required for the generation of antifungal CD8(+) T cell effectors during
      pulmonary C. neoformans infection. Using a murine intratracheal infection model,
      our results demonstrated that CD4(+) T cells were not required for the expansion
      and trafficking of CD8(+) T cells to the site of infection. CD4(+) T cells were
      also not required for the generation of IFN-gamma-producing CD8(+) T cell
      effectors in the lungs. In CD4(-) mice, depletion of CD8(+) T cells resulted in
      increased intracellular infection of pulmonary macrophages by C. neoformans,
      increasing the pulmonary burden of the infection. Neutralization of IFN-gamma in
      CD4(-)CD8(+) mice similarly increased macrophage infection by C. neoformans,
      thereby blocking the protection provided by CD8(+) T cells. Altogether, these
      data support the hypothesis that effector CD8(+) T cell function is independent
      of CD4(+) T cells and that IFN-gamma production from CD8(+) T cells plays a role
      in controlling C. neoformans by limiting survival of C. neoformans within
      macrophages.

PMID- 15944299
TI  - FliC-specific CD4+ T cell responses are restricted by bacterial regulation of
      antigen expression.
AB  - Salmonella typhimurium, a facultatively intracellular pathogen, regulates
      expression of virulence factors in response to distinct environments encountered
      during the course of infection. We tested the hypothesis that the transition from
      extra- to intracellular environments during Salmonella infection triggers changes
      in Ag expression that impose both temporal and spatial limitations on the host T
      cell response. CD4(+) T cells recovered from Salmonella immune mice were
      propagated in vitro using Ag derived from bacteria grown in conditions designed
      to emulate extra- or intracellular environments in vivo. Extracellular phase
      bacteria supported a dominant T cell response to the flagellar subunit protein
      FliC, whereas intracellular phase bacteria were unable to support expansion of
      FliC-specific T cells from populations known to contain T cells with reactivity
      to this Ag. This result was attributed to bacterial regulation of FliC
      expression: transcription and protein levels were repressed in bacteria growing
      in the spleens of infected mice. Furthermore, Salmonella-infected splenocytes
      taken directly ex vivo stimulated FliC-specific T cell clones only when
      intracellular FliC expression was artificially up-regulated. Although it has been
      suggested that a microanatomical separation of immune T cells and infected APC
      exists in vivo, we demonstrate that intracellular Salmonella can repress FliC
      expression below the T cell activation threshold. This potentially provides a
      mechanism for intracellular Salmonella at systemic sites to avoid detection by Ag
      specific T cells primed at intestinal sites early in infection.

PMID- 15944300
TI  - Inhibition of MAPK and NF-kappa B pathways is necessary for rapid apoptosis in
      macrophages infected with Yersinia.
AB  - Macrophages respond to infection with pathogenic Yersinia species by activating
      MAPK- and NF-kappaB-signaling pathways. To counteract this response, Yersiniae
      secrete a protease (Yersinia outer protein J (YopJ)) that is delivered into
      macrophages, deactivates MAPK- and NF-kappaB-signaling pathways, and induces
      apoptosis. NF-kappaB promotes cell survival by up-regulating expression of
      several apoptosis inhibitor genes. Previous studies show that deactivation of the
      NF-kappaB pathway by YopJ is important for Yersinia-induced apoptosis. To
      determine whether deactivation of the NF-kappaB pathway is sufficient for
      Yersinia-induced apoptosis, two inhibitors of the NF-kappaB pathway, IkappaBalpha
      superrepressor or A20, were expressed in macrophages. Macrophages expressing
      these proteins were infected with Yersinia pseudotuberculosis strains that
      secrete functionally active or inactive forms of YopJ. Apoptosis levels were
      substantially higher (5- to 10-fold) when active YopJ was delivered into
      macrophages expressing IkappaBalpha superrepressor or A20, suggesting that
      deactivation of the NF-kappaB pathway is not sufficient for rapid Yersinia
      induced apoptosis. When macrophages expressing A20 were treated with specific
      inhibitors of MAPKs, similar levels of apoptosis (within approximately 2-fold)
      were observed when active or inactive YopJ were delivered during infection. These
      results suggest that MAPK and NF-kappaB pathways function together to up-regulate
      apoptosis inhibitor gene expression in macrophages in response to Yersinia
      infection and that YopJ deactivates both pathways to promote rapid apoptosis. In
      addition, treating macrophages with a proteasome inhibitor results in higher
      levels of infection-induced apoptosis than can be achieved by blocking NF-kappaB
      function alone, suggesting that proapoptotic proteins are stabilized when
      proteasome function is blocked in macrophages.

PMID- 15944301
TI  - Late priming and variability of epitope-specific CD8+ T cell responses during a
      persistent virus infection.
AB  - Control of persistently infecting viruses requires that antiviral CD8(+) T cells
      sustain their numbers and effector function. In this study, we monitored epitope
      specific CD8(+) T cells during acute and persistent phases of infection by
      polyoma virus, a mouse pathogen that is capable of potent oncogenicity. We
      identified several novel polyoma-specific CD8(+) T cell epitopes in C57BL/6 mice,
      a mouse strain highly resistant to polyoma virus-induced tumors. Each of these
      epitopes is derived from the viral T proteins, nonstructural proteins produced by
      both productively and nonproductively (and potentially transformed) infected
      cells. In contrast to CD8(+) T cell responses described in other microbial
      infection mouse models, we found substantial variability between epitope-specific
      CD8(+) T cell responses in their kinetics of expansion and contraction during
      acute infection, maintenance during persistent infection, as well as their
      expression of cytokine receptors and cytokine profiles. This epitope-dependent
      variability also extended to differences in maturation of functional avidity from
      acute to persistent infection, despite a narrowing in TCR repertoire across all
      three specificities. Using a novel minimal myeloablation-bone marrow chimera
      approach, we visualized priming of epitope-specific CD8(+) T cells during
      persistent virus infection. Interestingly, epitope-specific CD8(+) T cells
      differed in CD62L-selectin expression profiles when primed in acute or persistent
      phases of infection, indicating that the context of priming affects CD8(+) T cell
      heterogeneity. In summary, persistent polyoma virus infection both quantitatively
      and qualitatively shapes the antiviral CD8(+) T cell response.

PMID- 15944302
TI  - Retinoic acid and polyriboinosinic:polyribocytidylic acid stimulate robust anti
      tetanus antibody production while differentially regulating type 1/type 2
      cytokines and lymphocyte populations.
AB  - Retinoic acid (RA), a bioactive retinoid, and polyriboinosinic:polyribocytidylic
      acid (PIC) are known to promote immunity in vitamin A-deficient animals. In this
      study, we hypothesized that RA, PIC, and the combination can provide significant
      immunoadjuvant activity even in the vitamin A-adequate state. Six-week-old
      C57BL/6 mice were immunized with tetanus toxoid (TT) and treated with RA and/or
      PIC at priming in three independent studies of short and long duration. RA and
      PIC differentially regulated both primary and secondary anti-TT IgG isotypes,
      whereas the combination of RA + PIC stimulated the highest level of anti-TT IgG
      production and, concomitantly, a ratio of IgG1 to IgG2a similar to that of the
      control group. The regulation of Ab response was strongly associated with type
      1/type 2 cytokine gene expression. Whereas RA reduced type 1 cytokines (IFN-gamma
      and IL-12), PIC enhanced both type 1 and type 2 cytokines (IL-4 and IL-12) and
      cytokine-related transcription factors. Despite the presence of PIC, the IL-4:IFN
      gamma ratio was significantly elevated by RA. In addition, RA and/or PIC
      modulated NK/NKT cell populations and the level of expression of the
      costimulatory molecules CD80/CD86, evident 3 days after priming. Notably, the
      NKT:NK and CD80:CD86 ratios were correlated with the IL-4:IFN-gamma ratio,
      indicative of multiple converging modes of regulation. Overall, RA, PIC, and RA +
      PIC rapidly and differentially shaped the anti-tetanus Ig response. The robust,
      durable, and proportionate increase in all anti-TT IgG isotypes induced by RA +
      PIC suggests that this combination is promising as a means to enhance the Ab
      response to TT and similar vaccines.

PMID- 15944303
TI  - In vivo modulation of T cell responses and protective immunity by TCR antagonism
      during infection.
AB  - Infectious agents are known to express altered peptide ligands that antagonize T
      cells in vitro; however, direct evidence of TCR antagonism during infection is
      still lacking, and its importance in the context of infection remains to be
      established. In this study, we used a murine model of infection with recombinant
      Listeria monocytogenes and addressed three issues that are critical for assessing
      the role of TCR antagonism in the modulation of the immune response. First, we
      demonstrated that the antagonist peptide efficiently inhibited the ability of the
      agonist to prime naive TCR-transgenic T cells in vivo. Second, we showed clonal
      memory T cells were antagonized during recall responses, resulting in loss of
      protective immunity. Lastly, we observed that even in the context of a polyclonal
      response, TCR antagonism greatly inhibits the agonist-specific response, leading
      to altered hierarchy of immunodominance and reduced T cell memory and protective
      immunity. These results provide direct evidence of clonal TCR antagonism of naive
      and memory CD8 T cells during infection and demonstrate the effect of TCR
      antagonism on protective immunity. Thus, agonist/antagonist interactions may play
      an important role in determining the immunodominance and repertoire of T cell
      targets, and evaluation of immune responses and vaccine strategies may require
      examination of not only agonists but also antagonists and their interactions
      during an infection.

PMID- 15944304
TI  - Severe acute respiratory syndrome and the innate immune responses: modulation of
      effector cell function without productive infection.
AB  - Severe acute respiratory syndrome (SARS) caused by a novel human coronavirus
      (CoV), designated SARS-CoV, is a highly contagious respiratory disease with the
      lungs as a major target. Although the exact mechanism of SARS-CoV pathogenesis
      remains unknown, an intense, ill-regulated local inflammatory response has been
      suggested as partially responsible for the devastating lung pathology. We
      investigated the interaction of SARS-CoV with human macrophages (Mphi) and
      dendritic cells (DC), two key innate immune cells of the host immune system, by
      focusing on their susceptibility to viral infection and subsequent responses
      (e.g., phenotypic maturation, T cell-priming activity, phagocytosis, and cytokine
      production). We found neither cell to be permissive for SARS-CoV replication.
      However, incubation of Mphi and DC with live, but not gamma irradiation
      inactivated, viruses appeared to better sustain their viability. Also, exposure
      to infectious SARS-CoV led to the phenotypic and functional maturation of DC,
      with regard to MHC class II and costimulatory molecule expression, T cell
      stimulatory capacity, and cytokine production, respectively. Cytokine production
      was also observed for Mphi, which were refractory to cell surface phenotypic
      changes. Strikingly, live SARS-CoV could further prime cell types to respond to a
      suboptimal dose of bacterial LPS (100 ng/ml), resulting in massive release of IL
      6 and IL-12. However, the endocytic capacity (e.g., Ag capture) of Mphi was
      significantly compromised upon exposure to infectious SARS-CoV. This study is the
      first demonstration that although SARS-CoV does not productively infect human
      Mphi or DC, it appears to exert differential effects on Mphi and DC maturation
      and functions, which might contribute to SARS pathogenesis.

PMID- 15944305
TI  - Mechanisms of mucosal and parenteral tuberculosis vaccinations: adenoviral-based
      mucosal immunization preferentially elicits sustained accumulation of immune
      protective CD4 and CD8 T cells within the airway lumen.
AB  - The mechanisms underlying better immune protection by mucosal vaccination have
      remained poorly understood. In our current study we have investigated the
      mechanisms by which respiratory virus-mediated mucosal vaccination provides
      remarkably better immune protection against pulmonary tuberculosis than
      parenteral vaccination. A recombinant adenovirus-based tuberculosis (TB) vaccine
      expressing Mycobacterium tuberculosis Ag85A (AdAg85A) was administered either
      intranasally (i.n.) or i.m. to mice, and Ag-specific CD4 and CD8 T cell
      responses, including frequency, IFN-gamma production, and CTL, were examined in
      the spleen, lung interstitium, and airway lumen. Although i.m. immunization with
      AdAg85A led to activation of T cells, particularly CD8 T cells, in the spleen
      and, to a lesser extent, in the lung interstitium, it failed to elicit any T cell
      response in the airway lumen. In contrast, although i.n. immunization failed to
      effectively activate T cells in the spleen, it uniquely elicited higher numbers
      of Ag-specific CD4 and CD8 T cells in the airway lumen that were capable of IFN
      gamma production and cytolytic activities, as assessed by an intratracheal in
      vivo CTL assay. These airway luminal T cells of i.n. immunized mice or splenic T
      cells of i.m. immunized mice, upon transfer locally to the lungs of naive SCID
      mice, conferred immune protection against M. tuberculosis challenge. Our study
      has demonstrated that the airway luminal T cell population plays an important
      role in immune protection against pulmonary TB, thus providing mechanistic
      insights into the superior immune protection conferred by respiratory mucosal TB
      vaccination.

PMID- 15944306
TI  - Neisseria gonorrhoeae enhances infection of dendritic cells by HIV type 1.
AB  - Clinical studies indicate that Neisseria gonorrhoeae (gonococci (GC)) has the
      capacity to enhance HIV type 1 (HIV-1) infection. We studied whether GC enhances
      HIV infection of activated dendritic cells (DCs). The results show that GC can
      dramatically enhance HIV replication in human DCs during coinfection. The GC
      component responsible for HIV infection enhancement may be peptidoglycan, which
      activates TLR2. TLR2 involvement is suggested by bacterial lipoprotein, a TLR2
      specific inducer, which stimulates a strong enhancement of HIV infection by human
      DCs. Moreover, participation of TLR2 is further implicated because GC is unable
      to stimulate expression of HIV in DCs of TLR2-deficient HIV-1-transgenic mice.
      These results provide one potential mechanism through which GC infection
      increases HIV replication in patients infected with both GC and HIV.

PMID- 15944307
TI  - Deficiency of dermcidin-derived antimicrobial peptides in sweat of patients with
      atopic dermatitis correlates with an impaired innate defense of human skin in
      vivo.
AB  - Antimicrobial peptides are an integral part of the epithelial innate defense
      system. Dermcidin (DCD) is a recently discovered antimicrobial peptide with a
      broad spectrum of activity. It is constitutively expressed in human eccrine sweat
      glands and secreted into sweat. Patients with atopic dermatitis (AD) have
      recurrent bacterial or viral skin infections and pronounced colonization with
      Staphylococcus aureus. We hypothesized that patients with AD have a reduced
      amount of DCD peptides in sweat contributing to the compromised constitutive
      innate skin defense. Therefore, we performed semiquantitative and quantitative
      analyses of DCD peptides in sweat of AD patients and healthy subjects using
      surface-enhanced laser desorption ionization time-of-flight mass spectrometry and
      ELISA. The data indicate that the amount of several DCD-derived peptides in sweat
      of patients with AD is significantly reduced. Furthermore, compared with atopic
      patients without previous infectious complications, AD patients with a history of
      bacterial and viral skin infections were found to have significantly less DCD-1
      and DCD-1L in their sweat. To analyze whether the reduced amount of DCD in sweat
      of AD patients correlates with a decreased innate defense, we determined the
      antimicrobial activity of sweat in vivo. We showed that in healthy subjects,
      sweating leads to a reduction of viable bacteria on the skin surface, but this
      does not occur in patients with AD. These data indicate that reduced expression
      of DCD in sweat of patients with AD may contribute to the high susceptibility of
      these patients to skin infections and altered skin colonization.

PMID- 15944308
TI  - Phosphatidylinositol-specific phospholipase C of Bacillus anthracis down
      modulates the immune response.
AB  - Phosphatidylinositol-specific phospholipases (PI-PLCs) are virulence factors
      produced by many pathogenic bacteria, including Bacillus anthracis and Listeria
      monocytogenes. Bacillus PI-PLC differs from Listeria PI-PLC in that it has strong
      activity for cleaving GPI-anchored proteins. Treatment of murine DCs with
      Bacillus, but not Listeria, PI-PLC inhibited dendritic cell (DC) activation by
      TLR ligands. Infection of mice with Listeria expressing B. anthracis PI-PLC
      resulted in a reduced Ag-specific CD4 T cell response. These data indicate that
      B. anthracis PI-PLC down-modulates DC function and T cell responses, possibly by
      cleaving GPI-anchored proteins important for TLR-mediated DC activation.

PMID- 15944309
TI  - Mouse genetic background is a major determinant of isotype-related differences
      for antibody-mediated protective efficacy against Cryptococcus neoformans.
AB  - The protective efficacy of mAbs to Cryptococcus neoformans glucuronoxylomannan
      depends on Ab isotype. Previous studies in A/JCr and C57BL/6J mice showed
      relative protective efficacy of IgG1, IgG2a >> IgG3. However, we now report that
      in C57BL/6J x 129/Sv mice, IgG3 is protective while IgG1 is not protective, with
      neither isotype being protective in 129/Sv mice. IgG1, IgG2a, and IgG3 had
      different effects on IFN-gamma expression in infected C57BL/6J x 129/Sv mice.
      IgG1-treated C57BL/6J x 129/Sv mice had significantly more pulmonary eosinophilia
      than IgG2a- and IgG3-treated C57BL/6J x 129/Sv mice. C. neoformans infection and
      Ab administration had different effects on FcgammaRI, FcgammaRII, and FcgammaRIII
      expression in C57BL/6J, 129/Sv, and C57BL/6J x 129/Sv mice. Our results indicate
      that the relative efficacy of Ab isotype function against C. neoformans is a
      function of the genetic background of the host and that IgG3-mediated protection
      in C57BL/6J x 129/Sv mice was associated with lower levels of IFN-gamma and fewer
      pulmonary eosinophils. The dependence of isotype efficacy on host genetics
      underscores a previously unsuspected complex relationship between the cellular
      and humoral arms of the adaptive immune response.

PMID- 15944310
TI  - Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by
      preventing the apoptosis of activated CD1d-restricted NKT cells.
AB  - Fulminant liver failure (FLF) consists of a cascade of events beginning with a
      presumed uncontrolled systemic activation of the immune system. The etiology of
      FLF remains undefined. In this study, we demonstrate that CCR5 deficiency
      promotes the development of acute FLF in mice following Con A administration by
      preventing activated hepatic CD1d-restricted NKT cells (but not conventional T
      cells) from dying from activation-induced apoptosis. The resistance of CCR5
      deficient NKT cells from activation-induced apoptosis following Con A
      administration is not due to a defective Fas-driven death pathway. Moreover, FLF
      in CCR5-deficient mice also correlated with hepatic CCR5-deficient NKT cells,
      producing more IL-4, but not IFN-gamma, relative to wild-type NKT cells.
      Furthermore, FLF in these mice was abolished by IL-4 mAb or NK1.1 mAb treatment.
      We propose that CCR5 deficiency may predispose individuals to the development of
      FLF by preventing hepatic NKT cell apoptosis and by regulating NKT cell function,
      establishing a novel role for CCR5 in the development of this catastrophic liver
      disease that is independent of leukocyte recruitment.

PMID- 15944311
TI  - Stage-specific expression of surface antigens by Toxoplasma gondii as a mechanism
      to facilitate parasite persistence.
AB  - Toxoplasma persists in the face of a functional immune system. This success
      critically depends on the ability of parasites to activate a strong adaptive
      immune response during acute infection with tachyzoites that eliminates most of
      the parasites and to undergo stage conversion to bradyzoites that encyst and
      persist predominantly in the brain. A dramatic change in antigenic composition
      occurs during stage conversion, such that tachyzoites and bradyzoites express
      closely related but antigenically distinct sets of surface Ags belonging to the
      surface Ag 1 (SAG1)-related sequence (SRS) family. To test the contribution of
      this antigenic switch to parasite persistence, we engineered parasites to
      constitutively express the normally bradyzoite-specific SRS9 (SRS9(c)) mutants
      and tachyzoite-specific SAG1 (SAG1(c)) mutants. SRS9(c) but not wild-type
      parasites elicited a SRS9-specific immune response marked by IFN-gamma
      production, suggesting that stage-specificity of SRS Ags determines their
      immunogenicity in infection. The induction of a SRS9-specific immune response
      correlated with a continual decrease in the number of SRS9(c) cysts persisting in
      the brain. In contrast, SAG1(c) mutants produced reduced brain cyst loads early
      in chronic infection, but these substantially increased over time accompanying a
      hyperproduction of IFN-gamma, TNF-alpha, and IL-10, and severe encephalitis. We
      conclude that stage-specific expression of SRS Ags is among the key mechanisms by
      which optimal parasite persistency is established and maintained.

PMID- 15944312
TI  - Critical role of proline-rich tyrosine kinase 2 in reversion of the adhesion
      mediated suppression of reactive oxygen species generation by human neutrophils.
AB  - Neutrophils act as the first line of innate immune defense against invading
      microorganisms during infection and inflammation. The tightly regulated
      production of reactive oxygen species (ROS) through activation of NADPH oxidase
      is a major weapon used by neutrophils and other phagocytic leukocytes to combat
      such pathogens. Cellular adhesion signals play important physiological roles in
      regulating the activation of NADPH oxidase and subsequent ROS formation. We
      previously showed that the initial suppression of the oxidase response of
      chemoattractant-stimulated adherent neutrophils is mediated via inhibition of
      Vav1-induced activation of the NADPH oxidase regulatory GTPase Rac2 by adhesion
      signals. In this study we show that prior exposure of neutrophils to a number of
      cytokines and inflammatory mediators, including TNF-alpha, GM-CSF, and platelet
      activating factor, overcomes the adhesion-mediated suppression of ROS formation.
      Proline-rich tyrosine kinase 2 (pyk2) activity is enhanced under these
      conditions, correlating with the restoration of Vav1 and Rac2 activities. Both
      dominant negative pyk2 and a pyk2-selective inhibitor prevented restoration of
      ROS production induced by TNF-alpha, GM-CSF, and platelet-activating factor, and
      this loss of pyk2 activity resulted in decreased Vav1 tyrosine phosphorylation
      and subsequent Rac2 activation. Our studies identify pyk2 as a critical
      regulatory component and a molecular switch to overcome the suppression of
      leukocyte oxidant generation by cell adhesion. This activity constitutes a
      mechanism by which cytokines might lead to rapid elimination of invading
      pathogens by adherent neutrophils under normal conditions or enhance tissue
      damage in pathological states.

PMID- 15944313
TI  - The role of p38 MAPK in rhinovirus-induced monocyte chemoattractant protein-1
      production by monocytic-lineage cells.
AB  - Viral respiratory infections are a major cause of asthma exacerbations and can
      contribute to the pathogenesis of asthma. Major group human rhinovirus enters
      cells by binding to the cell surface molecule ICAM-1 that is present on
      epithelial and monocytic lineage cells. The focus of the resulting viral
      infection is in bronchial epithelia. However, previous studies of the cytokine
      dysregulation that follows rhinovirus infection have implicated monocytic lineage
      cells in establishing the inflammatory environment even though productive
      infection is not a result. We have determined that human alveolar macrophages and
      human peripheral blood monocytes release MCP-1 upon exposure to human rhinovirus
      16 (HRV16). Indeed, we have found p38 MAPK activation in human alveolar
      macrophages within 15 min of exposure to HRV16, and this activation lasts up to 1
      h. The targets of p38 MAPK activation include transcriptional activators of the
      MCP-1 promoter. The transcription factor ATF-2, a p38 MAPK substrate, is
      phosphorylated 45 min after HRV16 exposure. Furthermore, IkappaBalpha, the
      inhibitor of the transcription factor NF-kappaB, is degraded. Prevention of HRV16
      binding was effective in blocking p38 MAPK activation, ATF-2 phosphorylation, and
      MCP-1 release. This is the first report of a relationship between HRV16 exposure,
      MCP-1 release and monocytic-lineage cells suggesting that MCP-1 plays a role in
      establishing the inflammatory microenvironment initiated in the human airway upon
      exposure to rhinovirus.

PMID- 15944314
TI  - Involvement of SHIP in TLR2-induced neutrophil activation and acute lung injury.
AB  - The SHIP converts phosphatidylinositol 3,4,5 triphosphate to phosphatidyl 3,4
      biphosphate. SHIP has negative regulatory functions on PI3K-dependent signaling
      pathways, which occupy important roles in modulating neutrophil functions. We
      used neutrophils from transgenic SHIP(-/-) and SHIP(+/+) mice that were
      stimulated with peptidoglycan (PGN) to examine the role of SHIP in TLR2-induced
      neutrophil activation. SHIP(-/-) neutrophils demonstrated significantly increased
      activation of the PI3K-dependent kinase Akt after exposure to PGN. Release of
      cytokines and chemokines, including TNF-alpha, IL-1beta, IL-6, IL-10, and MIP-2,
      was also increased in SHIP(-/-) compared with SHIP(+/+) neutrophils. There was no
      difference in the nuclear translocation of the transcriptional factor NF-kappaB
      between PGN-stimulated SHIP(-/-) and SHIP(+/+) neutrophils. However,
      phosphorylation of the p65 subunit of NF-kappaB, an event essential for optimal
      transcriptional activity of NF-kappaB, was increased in TLR2-activated SHIP(-/-)
      neutrophils. SHIP(-/-) neutrophils demonstrated greater activation of ERK1/2 and
      p38 MAPKs than did SHIP(+/+) neutrophils after exposure to PGN. The severity of
      acute lung injury induced by PGN was greater in SHIP(-/-) as compared with
      SHIP(+/+) mice. These results demonstrate that SHIP has a negative regulatory
      role in TLR2-induced neutrophil activation and in the development of related in
      vivo neutrophil-dependent inflammatory processes, such as acute lung injury.

PMID- 15944315
TI  - Monocyte adhesion to xenogeneic endothelium during laminar flow is dependent on
      alpha-Gal-mediated monocyte activation.
AB  - Monocytes are the predominant inflammatory cell recruited to xenografts and
      participate in delayed xenograft rejection. In contrast to allogeneic leukocytes
      that require up-regulation of endothelial adhesion molecules to adhere and
      emigrate into effector tissues, we demonstrate that human monocytes adhere
      rapidly to unstimulated xenogeneic endothelial cells. The major xenoantigen
      galactosealpha(1,3)galactosebeta(1,4)GlcNAc-R (alpha-gal) is abundantly expressed
      on xenogeneic endothelium. We have identified a putative receptor for alpha-gal
      on human monocytes that is a member of the C-type family of lectin receptors.
      Monocyte arrest under physiological flow conditions is regulated by alpha-gal,
      because cleavage or blockade results in a dramatic reduction in monocyte
      adhesion. Recruitment of human monocytes to unactivated xenogeneic endothelial
      cells requires both alpha(4) and beta(2) integrins on the monocyte; binding of
      alpha-gal to monocytes results in rapid activation of beta(2), but not alpha(4),
      integrins. Thus, activation of monocyte beta(2) integrins by alpha-gal expressed
      on xenogeneic endothelium provides a mechanism that may explain the dramatic
      accumulation of monocytes in vivo.

PMID- 15944316
TI  - Evidence for a role of phosphodiesterase 4 in lipopolysaccharide-stimulated
      prostaglandin E2 production and matrix metalloproteinase-9 activity in human
      amniochorionic membranes.
AB  - Chorioamniotic infection is a leading cause of preterm premature rupture of fetal
      membranes (amnion and chorion). Bacterial infection induces an inflammatory
      response characterized by elevated production of proinflammatory cytokines; the
      latter activate the production of both PGs that stimulate uterine contractions,
      and matrix metalloproteinases (MMPs) that degrade the extracellular matrix of the
      chorioamniotic membranes. The inflammatory response is under the control of cAMP
      content, which is partly regulated by phosphodiesterases (PDE). In this study, we
      investigated the role of the PDE4 family in the inflammatory process triggered by
      LPS in a model of amniochorionic explants. We found that PDE4 family is the major
      cAMP-PDE expressed in human fetal membranes and that PDE4 activity is increased
      by LPS treatment. Selective inhibition of PDE4 activity affected LPS signaling,
      because PDE4 inhibitors (rolipram and/or cilomilast) reduced the release of the
      proinflammatory cytokine TNF-alpha and increased the release of the anti
      inflammatory cytokine IL-10. PDE4 inhibition reduced cyclooxygenase-2 protein
      expression and PGE(2) production and also modulated MMP-9, a key mediator of the
      membrane rupture process, by inhibiting pro-MMP-9 mRNA expression and pro-MMP-9
      activity. These results demonstrate that the PDE4 family participates in the
      regulation of the inflammatory response associated with fetal membrane rupture
      during infection. The PDE4 family may be an appropriate pharmacological target
      for the management of infection-induced preterm delivery.

PMID- 15944317
TI  - Apoptotic pathways are inhibited by leptin receptor activation in neutrophils.
AB  - Leptin regulates food intake as well as metabolic, endocrine, and immune
      functions. It exerts proliferative and antiapoptotic activities in a variety of
      cell types, including T cells. Leptin also stimulates macrophages and
      neutrophils, and its production is increased during inflammation. In this study,
      we demonstrate that human neutrophils express leptin surface receptors under in
      vitro and in vivo conditions, and that leptin delays apoptosis of mature
      neutrophils in vitro. The antiapoptotic effects of leptin were concentration
      dependent and blocked by an anti-leptin receptor mAb. The efficacy of leptin to
      block neutrophil apoptosis was similar to G-CSF. Using pharmacological
      inhibitors, we obtained evidence that leptin initiates a signaling cascade
      involving PI3K- and MAPK-dependent pathways in neutrophils. Moreover, leptin
      delayed the cleavage of Bid and Bax, the mitochondrial release of cytochrome c
      and second mitochondria-derived activator of caspase, as well as the activation
      of both caspase-8 and caspase-3 in these cells. Taken together, leptin is a
      survival cytokine for human neutrophils, a finding with potential pathologic
      relevance in inflammatory diseases.

PMID- 15944318
TI  - IL-13 regulates the immune response to inhaled antigens.
AB  - The large inhibitory effect of IL-13 blockers on the asthma phenotype prompted us
      to ask whether IL-13 would play a role in regulating the allergic immune response
      in addition to its documented effects on structural pulmonary cells. Because IL
      13 does not interact with murine T or B cells, but with monocytes, macrophages,
      and dendritic cells (DCs), we examined the role of IL-13 in the activation of
      pulmonary macrophages and DCs and in the priming of an immune response to a
      harmless, inhaled Ag. We found that a majority of cells called "alveolar or
      interstitial macrophages" express CD11c at high levels (CD11c(high)) and are a
      mixture of at least two cell types as follows: 1) cells of a mixed phenotype
      expressing DC and macrophage markers (CD11c, CD205, and F4/80) but little MHC
      class II (MHC II); and 2) DC-like cells expressing CD11c, CD205, MHC II, and
      costimulatory molecules. Endogenous IL-13 was necessary to induce and sustain the
      increase in MHC II and CD40 expression by pulmonary CD11c(high) cells,
      demonstrated by giving an IL-13 inhibitor as a measure of prevention or reversal
      to allergen-primed and -challenged mice. Conversely, IL-13 given by inhalation to
      naive mice increased the expression of MHC II and costimulatory molecules by
      CD11c(high) cells in an IL-4Ralpha-dependent manner. We found that exogenous IL
      13 exaggerated the immune and inflammatory responses to an inhaled, harmless Ag,
      whereas endogenous IL-13 was necessary for the priming of naive mice with an
      inhaled, harmless Ag. These data indicate that blockade of IL-13 may have
      therapeutic potential for controlling the immune response to inhaled Ags.

PMID- 15944319
TI  - Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced
      alveolar remodeling and pulmonary emphysema.
AB  - Th1/Tc1 inflammation and remodeling responses characterized by tissue atrophy and
      destruction frequently coexist in human diseases and disorders. However, the
      mechanisms that are used by Th1/Tc1 cytokines, like IFN-gamma, to induce these
      responses have not been defined. To elucidate the mechanism(s) of IFN-gamma
      induced tissue remodeling and destruction, we characterized the pathway that lung
      targeted, transgenic IFN-gamma uses to induce alveolar remodeling in a murine
      pulmonary emphysema modeling system. In these mice, transgenic IFN-gamma caused
      epithelial cell DNA injury and apoptosis detectable with TUNEL (Roche) and dual
      annexin V and propidium iodide staining. These responses were associated with
      death receptor and mitochondrial apoptosis pathway activation. Importantly,
      apoptosis inhibition with a caspase inhibitor (N-benzylcarboxy-Val-Ala-Asp
      fluoromethyl-ketone) or a null mutation of caspase-3 blocked this DNA injury and
      apoptosis response and significantly ameliorated IFN-gamma-induced emphysema.
      These interventions also ameliorated IFN-gamma-induced inflammation and decreased
      pulmonary protease burden. Selective cathepsin S inhibition and a null mutation
      of cathepsin S also decreased IFN-gamma-induced DNA injury, apoptosis, emphysema,
      inflammation, and protease accumulation. These studies demonstrate that cathepsin
      S-dependent epithelial cell apoptosis is a critical event in the pathogenesis of
      IFN-gamma-induced alveolar remodeling and emphysema. They also link inflammation,
      protease/antiprotease alterations, and protease-dependent apoptosis in the
      pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive
      responses.

PMID- 15944320
TI  - Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and
      translocation of NF-kappa B as potential targets.
AB  - Curcumin has been shown to exhibit anti-inflammatory, antimutagenic, and
      anticarcinogenic activities. However, the effect of curcumin on the maturation
      and immunostimulatory function of dendritic cells (DC) largely remains unknown.
      In this study, we examined whether curcumin can influence surface molecule
      expression, cytokine production, and their underlying signaling pathways in
      murine bone marrow-derived DC. DC were derived from murine bone marrow cells and
      used as immature or LPS-stimulated mature cells. The DC were tested for surface
      molecule expression, cytokine production, dextran uptake, the capacity to induce
      T cell differentiation, and their underlying signaling pathways. Curcumin
      significantly suppressed CD80, CD86, and MHC class II expression, but not MHC
      class I expression, in the DC. The DC also exhibited impaired IL-12 expression
      and proinflammatory cytokine production (IL-1beta, IL-6, and TNF-alpha). The
      curcumin-treated DC were highly efficient at Ag capture, via mannose receptor
      mediated endocytosis. Curcumin inhibited LPS-induced MAPK activation and the
      translocation of NF-kappaB p65. In addition, the curcumin-treated DC showed an
      impaired induction of Th1 responses and a normal cell-mediated immune response.
      These novel findings provide new insight into the immunopharmacological role of
      curcumin in impacting on the DC. These novel findings open perspectives for the
      understanding of the immunopharmacological role of curcumin and therapeutic
      adjuvants for DC-related acute and chronic diseases.

PMID- 15944321
TI  - Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis,
      and contact hypersensitivity and the effects of proteasome inhibition.
AB  - Acute phase serum amyloid A proteins (A-SAAs) are multifunctional apolipoproteins
      produced in large amounts during the acute phase of an inflammation and also
      during the development of chronic inflammatory diseases. In this study we present
      a Saa1-luc transgenic mouse model in which SAA1 gene expression can be monitored
      by measuring luciferase activity using a noninvasive imaging system. When
      challenged with LPS, TNF-alpha, or IL-1beta, in vivo imaging of Saa1-luc mice
      showed a 1000- to 3000-fold induction of luciferase activity in the hepatic
      region that peaked 4-7 h after treatment. The induction of liver luciferase
      expression was consistent with an increase in SAA1 mRNA in the liver and a
      dramatic elevation of the serum SAA1 concentration. Ex vivo analyses revealed
      luciferase induction in many tissues, ranging from several-fold (brain) to >5000
      fold (liver) after LPS or TNF-alpha treatment. Pretreatment of mice with the
      proteasome inhibitor bortezomib significantly suppressed LPS-induced SAA1
      expression. These results suggested that proteasome inhibition, perhaps through
      the NF-kappaB signaling pathway, may regulate SAA1 expression. During the
      development of acute arthritis triggered by intra-articular administration of
      zymosan, SAA1 expression was induced both locally at the knee joint and
      systemically in the liver, and the induction was significantly suppressed by
      bortezomib. Induction of SAA1 expression was also demonstrated during contact
      hypersensitivity induced by topical application of oxazolone. These results
      suggest that both local and systemic induction of A-SAA occur during inflammation
      and may contribute to the pathogenesis of chronic inflammatory diseases
      associated with amyloid deposition.

PMID- 15944322
TI  - Protection of plasminogen activator inhibitor-1-deficient mice from nasal
      allergy.
AB  - This study was performed to clarify the relationship between fibrinolytic
      components and the pathology of allergy, particularly that during the development
      of nasal allergy and nasal tissue changes. Intranasal OVA challenge after
      sensitization by i.p. administration of OVA induced a higher level of excess
      subepithelial collagen deposition in wild-type (WT) C57BL/6J mice than in
      plasminogen activator inhibitor (PAI)-1-deficient (PAI-1(-/-)) mice. The excess
      PAI-1 induction in the nasal mucosa and higher level of active PAI-1 in the nasal
      lavage fluid of WT-OVA mice compared with those in WT-control mice suggested that
      the decrease of proteolytic activity inhibits the removal of subepithelial
      collagen. The frequency of sneezing, nasal rubbing, nasal hyperresponsiveness,
      production of specific IgG1 and IgE in the serum, and production of IL-4 and IL-5
      in splenocyte culture supernatant increased significantly in WT-OVA mice. In PAI
      1(-/-) mice, these reactions were absent, and specific IgG2a in serum and IFN
      gamma in splenocyte culture medium increased significantly. Histopathologically,
      there were marked goblet cell hyperplasia and eosinophil infiltration into the
      nasal mucosa in WT-OVA mice, but these were absent in PAI-1(-/-) mice. These
      results indicate that the immune response in WT-OVA mice can be classified as a
      dominant Th2 response, which would promote collagen deposition. In contrast, the
      Th2 response in PAI-1(-/-) mice was down-regulated, and the immune response
      shifted from Th2-dominant reaction to a Th1-dominant one. Taken together, these
      findings suggest that PAI-1 plays an important role not only in thrombolysis but
      also in immune response.

PMID- 15944323
TI  - IgA antibodies impair resistance against Helicobacter pylori infection: studies
      on immune evasion in IL-10-deficient mice.
AB  - We recently reported that Helicobacter pylori-specific Abs impair the development
      of gastritis and down-regulate resistance against H. pylori infection. In this
      study, we asked whether IgA Abs specifically can have an impact on H. pylori
      colonization and gastric inflammation. To obtain a sensitive model for the study
      of inflammation we crossed IgA- and IL-10-deficient mice. We found that IL-10(-/
      )/IgA(-/-) mice were significantly less colonized than IL-10(-/-)/IgA(+/+) mice,
      which in turn were less colonized than wild-type (WT) mice. The IL-10(-/-)/IgA(-/
      ) mice exhibited a 1.2-log reduction in bacterial counts compared with that in IL
      10(-/-)/IgA(+/+) mice, suggesting that IgA Abs rather promoted than prevented
      infection. The reduced colonization in IL-10(-/-)/IgA(-/-) mice was associated
      with the most severe gastritis observed, albeit all IL-10(-/-) mice demonstrated
      more severe gastric inflammation than wild-type mice. The gastritis score and the
      infiltration of CD4(+) T cells into the gastric mucosa were significantly higher
      in IL-10(-/-)/IgA(-/-) mice than in IL-10(-/-)/IgA(+/+) mice, arguing that IgA
      Abs counteracted inflammation. Moreover, following oral immunization, IL-10(-/
      )/IgA(-/-) mice were significantly better protected against colonization than IL
      10(-/-)/IgA(+/+) mice. However, the stronger protection was associated with more
      severe postimmunization gastritis and gastric infiltration of CD4(+) T cells.
      There was also a clear increase in complement receptor-expressing cells in IL-10(
      /-)/IgA(-/-) mice, though C3b-fragment deposition in the gastric mucosa was
      comparable between the two. Finally, specific T cell responses to recall Ag
      demonstrated higher levels of IFN-gamma production in IL-10(-/-)/IgA(-/-) as
      compared with IL-10(-/-)/IgA(+/+) mice. Thus, it appears that IgA and IL-10 help
      H. pylori bacteria evade host resistance against infection.

PMID- 15944324
TI  - Mannose-containing molecular patterns are strong inducers of cyclooxygenase-2
      expression and prostaglandin E2 production in human macrophages.
AB  - The induction of cyclooxygenase-2 (COX-2) and the production of PGE(2) in
      response to pathogen-associated molecular patterns decorated with mannose
      moieties were studied in human monocytes and monocyte-derived macrophages (MDM).
      Saccharomyces cerevisiae mannan was a robust agonist, suggesting the involvement
      of the mannose receptor (MR). MR expression increased along the macrophage
      differentiation route, as judged from both its surface display assessed by flow
      cytometry and the ability of MDM to ingest mannosylated BSA. Treatment with
      mannose-BSA, a weak agonist of the MR containing a lower ratio of attached sugar
      compared with pure polysaccharides, before the addition of mannan inhibited COX-2
      expression, whereas this was not observed when agonists other than mannan and
      zymosan were used. HeLa cells, which were found to express MR mRNA, showed a
      significant induction of COX-2 expression upon mannan challenge. Conversely,
      mannan did not induce COX-2 expression in HEK293 cells, which express the mRNA
      encoding Endo180, a parent receptor pertaining to the MR family, but not the MR
      itself. These data indicate that mannan is a strong inducer of COX-2 expression
      in human MDM, most likely by acting through the MR route. Because COX-2 products
      can be both proinflammatory and immunomodulatory, these results disclose a
      signaling route triggered by mannose-decorated pathogen-associated molecular
      patterns, which can be involved in both the response to pathogens and the
      maintenance of homeostasis.

PMID- 15944325
TI  - Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via
      down-regulating Tyk2-STAT signaling in the human dendritic cell.
AB  - The immunopathogenesis mechanism of dengue virus (DV) infection remains elusive.
      We previously showed that the target of DV in humans is dendritic cells (DCs),
      the primary sentinels of immune system. We also observed that despite the
      significant amount of IFN-alpha induced; DV particles remain massively produced
      from infected DCs. It suggests that DV may antagonize the antiviral effect of IFN
      alpha. Recent work in animal studies demonstrated the differential critical roles
      of antiviral cytokines, namely IFN-alpha/IFN-beta and IFN-gamma, in blocking
      early viral production and in preventing viral-mediated disease, respectively. In
      this study, we examined the effects of IFN-alpha and IFN-gamma in DV infection of
      monocyte-derived DCs. We showed that the preinfection treatment with either IFN
      alpha or IFN-gamma effectively armed DCs and limited viral production in infected
      cells. However, after infection, DV developed mechanisms to counteract the
      protection from lately added IFN-alpha, but not IFN-gamma. Such a selective
      antagonism on antiviral effect of IFN-alpha, but not IFN-gamma, correlated with
      down-regulated tyrosine-phosphorylation and DNA-binding activities of STAT1 and
      STAT3 transcription factors by DV. Furthermore, subsequent studies into the
      underlying mechanisms revealed that DV attenuated IFN-alpha-induced tyrosine
      phosphorylation of Tyk2, an upstream molecule of STAT activation, but had no
      effect on expression of both IFN-alpha receptor 1 and IFN-alpha receptor 2.
      Moreover, DV infection by itself could activate STAT1 and STAT3 through IFN-alpha
      dependent and both IFN-alpha-dependent and IFN-alpha-independent mechanisms,
      respectively. These observations provide very useful messages with physiological
      significance in investigation of the pathogenesis, the defense mechanisms of
      human hosts and the therapeutic considerations in DV infection.

PMID- 15944326
TI  - The critical role of LIGHT in promoting intestinal inflammation and Crohn's
      disease.
AB  - Crohn's disease (CD) is a type of inflammatory bowel disease associated with
      increased Th1 cytokines and unique pathological features. However, its
      pathogenesis has not been fully understood. Previous studies showed that
      homologous to lymphotoxin, exhibits inducible expression, competes with
      herpesvirus glycoprotein D for HVEM on T cells (LIGHT) transgenic (Tg) mice
      develop autoimmunity including intestinal inflammation with a variable time
      course. In this study, we establish an experimental model for CD by adoptive
      transfer of Tg mesenteric lymph node cells into RAG(-/-) mice. The recipients of
      Tg lymphocytes rapidly develop a disease strikingly similar to the key pathologic
      features and cytokine characterization observed in CD. We demonstrate that, as a
      costimulatory molecule, LIGHT preferentially drives Th1 responses. LIGHT-mediated
      intestinal disease is dependent on both of its identified signaling receptors,
      lymphotoxin beta receptor and herpes virus entry mediator, because LIGHT Tg
      mesenteric lymph node cells do not cause intestinal inflammation when transferred
      into the lymphotoxin beta receptor-deficient mice, and herpes virus entry
      mediator on donor T cells is required for the full development of disease.
      Furthermore, we demonstrated that up-regulation of LIGHT is associated with
      active CD. These data establish a new mouse model resembling CD and suggest that
      up-regulation of LIGHT may be an important mediator of CD pathogenesis.

PMID- 15944328
TI  - Correlates of delayed disease progression in HIV-1-infected Kenyan children.
AB  - Without treatment most HIV-1-infected children in Africa die before their third
      birthday (>89%) and long-term nonprogressors are rare. The mechanisms underlying
      nonprogression in HIV-1-infected children are not well understood. In the present
      study, we examined potential correlates of delayed HIV disease progression in 51
      HIV-1-infected African children. Children were assigned to progression subgroups
      based on clinical characterization. HIV-1-specific immune responses were studied
      using a combination of ELISPOT assays, tetramer staining, and FACS analysis to
      characterize the magnitude, specificity, and functional phenotype of HIV-1
      specific CD8(+) and CD4(+) T cells. Host genetic factors were examined by
      genotyping with sequence-specific primers. HIV-1 nef gene sequences from
      infecting isolates from the children were examined for potential attenuating
      deletions. Thymic output was measured by T cell rearrangement excision circle
      assays. HIV-1-specific CD8(+) T cell responses were detected in all progression
      groups. The most striking attribute of long-term survivor nonprogressors was the
      detection of HIV-1-specific CD4(+) Th responses in this group at a magnitude
      substantially greater than previously observed in adult long-term nonprogressors.
      Although long-term survivor nonprogressors had a significantly higher percentage
      of CD45RA(+)CD4(+) T cells, nonprogression was not associated with higher thymic
      output. No protective genotypes for known coreceptor polymorphisms or large
      sequence deletions in the nef gene associated with delayed disease progression
      were identified. In the absence of host genotypes and attenuating mutations in
      HIV-1 nef, long-term surviving children generated strong CD4(+) T cell responses
      to HIV-1. As HIV-1-specific helper cells support anti-HIV-1 effector responses in
      active disease, their presence may be important in delaying disease progression.

PMID- 15944327
TI  - Thymic stromal lymphopoietin expression is increased in asthmatic airways and
      correlates with expression of Th2-attracting chemokines and disease severity.
AB  - Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines
      attracting Th2 T cells. We hypothesized that asthma is characterized by elevated
      bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting,
      chemokines as compared with controls, with selective accumulation of cells
      bearing receptors for these chemokines. We used in situ hybridization and
      immunohistochemistry to examine the expression and cellular provenance of TSLP,
      Th2-attracting (thymus and activation-regulated chemokine (TARC)/CCL17,
      macrophage-derived chemokine (MDC)/CCL22, I-309/CCL1) and Th1-attracting (IFN
      gamma-inducible protein 10 (IP-10)/CXCL10, IFN-inducible T cell alpha
      chemoattractant (I-TAC)/CXCL11) chemokines and expression of their receptors
      CCR4, CCR8, and CXCR3 in bronchial biopsies from 20 asthmatics and 15 normal
      controls. The numbers of cells within the bronchial epithelium and submucosa
      expressing mRNA for TSLP, TARC/CCL17, MDC/CCL22, and IP-10/CXCL10, but not I
      TAC/CXCL11 and I-309/CCL1, were significantly increased in asthmatics as compared
      with controls (p </= 0.018). TSLP and TARC/CCL17 expression correlated with
      airway obstruction. Although the total numbers of cells expressing CCR4, CCR8,
      and CXCR3 did not significantly differ in the asthmatics and controls, there was
      evidence of selective infiltration of CD4(+)/CCR4(+) T cells in the asthmatic
      biopsies which correlated with TARC and MDC expression and airway obstruction.
      Epithelial cells, endothelial cells, neutrophils, macrophages, and mast cells
      were significant sources of TSLP and chemokines. Our data implicate TSLP,
      TARC/CCL17, MDC/CCL22, and IP-10/CXCL10 in asthma pathogenesis. These may act
      partly through selective development and retention, or recruitment of Th2 cells
      bearing their receptors.

PMID- 15944329
TI  - Human BDCA-1-positive blood dendritic cells differentiate into phenotypically
      distinct immature and mature populations in the absence of exogenous maturational
      stimuli: differentiation failure in HIV infection.
AB  - Current immunological opinion holds that myeloid dendritic cell (mDC) precursors
      migrate from the blood to the tissues, where they differentiate into immature
      dermal- and Langerhans-type dendritic cells (DC). Tissue DC require appropriate
      signals from pathogens or inflammatory cytokines to mature and migrate to
      secondary lymphoid tissue. We show that purified blood mDC cultured in vitro with
      GM-CSF and IL-4, but in the absence of added exogenous maturation stimuli,
      rapidly differentiate into two maturational and phenotypically distinct
      populations. The major population resembles immature dermal DC, being positive
      for CD11b, CD1a, and DC-specific ICAM-3-grabbing nonintegrin. They express
      moderate levels of MHC class II and low levels of costimulatory molecules. The
      second population is CD11b(-/low) and lacks CD1a and DC-specific ICAM-3-grabbing
      nonintegrin but expresses high levels of MHC class II and costimulatory
      molecules. Expression of CCR7 on the CD11b(-/low) population and absence on the
      CD11b(+) cells further supports the view that these cells are mature and
      immature, respectively. Differentiation into mature and immature populations was
      not blocked by polymyxin B, an inhibitor of LPS. Neither population labeled for
      Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells.
      Stimulation of 48-h cultured DC with LPS, CD40L, or poly(I:C) caused little
      increase in MHC or costimulatory molecule expression in the CD11b(-/low) DC but
      caused up-regulated expression in the CD11b(+) cells. In HIV-infected
      individuals, there was a marked decrease in the viability of cultured blood mDC,
      a failure to differentiate into the two populations described for normal donors,
      and an impaired ability to stimulate T cell proliferation.

PMID- 15944330
TI  - Ex vivo characterization of multiepitopic tumor-specific CD8 T cells in patients
      with chronic myeloid leukemia: implications for vaccine development and adoptive
      cellular immunotherapy.
AB  - Identification of tumor-associated Ags is a prerequisite for vaccine-based and
      adoptive immune therapies. Some tumor-associated Ags elicit specific CD8 T cells
      in patients with chronic myeloid leukemia (CML). Here, we characterized ex vivo
      responses of CD8 T cells from CML patients to extrajunction bcr-abl peptides and
      telomerase 540-548 hTert, PR1, and WT1 peptides. CML-specific CD8 T cells were
      present in most treated patients and were usually multiepitopic: WT1, hTert, PR1,
      and bcr74 tetramer(+) cells were detected in 85, 82, 67, and 61% of patients,
      respectively. The breadth and magnitude of these responses did not differ
      significantly according to treatment or disease status. CML-specific tetramer(+)
      CD8 T cells had a predominantly memory phenotype, an intermediate perforin
      content, and low intracellular IFN-gamma accumulation in the presence of the
      relevant peptide. However, in short-term culture with HLA-matched leukemia cells,
      the patients' memory T cells were specifically reactivated to become IFN-gamma
      producing effector cells, suggesting that CD8 T cell precursors with lytic
      potential are present in vivo and can be activated by appropriate stimulation. In
      conclusion, this study shows that multiepitopic tumor-specific CD8 T cell
      responses occur naturally in most CML patients, opening the way to new strategies
      for enhancing anti-CML immunity, in particular in patients with minimal residual
      disease.

PMID- 15944331
TI  - Biochemical and physiological evidence that calmodulin is involved in the taste
      response of the sugar receptor cells of the blowfly, Phormia regina.
AB  - The gustatory system is essential for almost all animals. However, the signal
      transduction mechanisms have not yet been fully elucidated. We isolated labellar
      chemosensilla from blowfly, Phormia regina, and purified calcium binding proteins
      from the water soluble fraction. The most abundant calcium-binding protein was
      calmodulin. To investigate the role of calmodulin in taste transduction,
      electrophysiological responses were recorded with the calmodulin inhibitor, W-7.
      When we stimulated the labellar chemosensillum with sucrose plus W-7, a dose
      dependent decrease of impulse frequency was observed when the concentration was
      <50 microM. In addition, when W-7 at 50 microM or higher concentration was added,
      an initial short-term impulse generation from the sugar receptor cell was
      observed, but this was followed by a silent period. When the sensillum was
      stimulated with W-7 plus a membrane-permeable cGMP analog, dibtyryl-cGMP or 8
      bromo-cGMP, impulses of the sugar receptor cell were induced but the frequency
      was decreased. By the sidewall-recording method, we observed that the receptor
      potential induced by sucrose stimulation was decreased by W-7 in the sugar
      receptor cell, and corresponded with a disappearance of impulses. These data
      strongly suggest that the cGMP-gated channel generating receptor potential in the
      sugar receptor cell requires calmodulin for its gating.

PMID- 15944332
TI  - Albuminuria, just a marker for cardiovascular disease, or is it more?

PMID- 15944333
TI  - Association of metabolic syndrome in nondiabetic patients with increased risk for
      chronic kidney disease: the fat lady sings.

PMID- 15944334
TI  - Rapamycin: a new string to the antiproteinuric bow?

PMID- 15944335
TI  - Asymmetrical dimethylarginine predicts progression to dialysis and death in
      patients with chronic kidney disease: a competing risks modeling approach.
AB  - High plasma asymmetrical dimethylarginine (ADMA) signals endothelial dysfunction
      and atherosclerosis in the general population and predicts mortality in ESRD. The
      relationship among plasma levels of ADMA, renal function, and the risk for
      progression to ESRD (halving GFR or dialysis start) and death in an incident
      cohort of 131 patients with chronic kidney disease was investigated. Cox's
      competing risk regression was used to model double-failure times (progression to
      ESRD and death) as a function of ADMA. Covariates that were considered for
      adjustment included clinical characteristics, baseline GFR (Modification of Diet
      in Renal Disease equation 7 formula), proteinuria, traditional cardiovascular
      risk factors, serum C-reactive protein, homocysteine, and concomitant therapies.
      Mean age at enrollment was 71 +/- 11 yr, and 24% of patients had diabetes.
      Baseline GFR ranged from 8 to 77 ml/min per 1.73 m2 (average 31 +/- 15 ml/min per
      1.73 m2). ADMA was inversely related to GFR, ranking as the third predicting
      factor (partial r = -0.22, P = 0.01), after hemoglobin and urinary protein, in a
      general linear model that included multiple correlates of GFR. After a mean
      follow-up of 27 mo (range 3.4 to 36), 29 patients progressed to ESRD and 31 died.
      ADMA (hazard ratio per 0.1 muM/L 1.203; 95% confidence interval 1.071 to 1.350)
      predicted event occurrence independent of other potential confounders, including
      GFR, proteinuria, hemoglobin, and homocysteine. In patients with mild to advanced
      chronic kidney disease, plasma ADMA is inversely related to GFR and represents a
      strong and independent risk marker for progression to ESRD and mortality. These
      novel findings further expand the implications of previous observations in ESRD
      patients and generate hypotheses on the role of ADMA in progressive chronic
      nephropathies.

PMID- 15944336
TI  - Wnt-dependent beta-catenin signaling is activated after unilateral ureteral
      obstruction, and recombinant secreted frizzled-related protein 4 alters the
      progression of renal fibrosis.
AB  - beta-Catenin functions as a transducer of Wnt signals to the nucleus, where it
      interacts with the T cell factor (TCF) family of DNA binding proteins to regulate
      gene expression. On the basis of the genes regulated by beta-catenin and TCF in
      various biologic settings, two predicted functions of beta-catenin/TCF-dependent
      transcription are to mediate the loss of epithelial polarity and to promote
      fibroblast activities, such as the increased synthesis of fibronectin during
      chronic renal disease. These predictions were tested by determination of the
      expression and function of an inhibitor of Wnt signaling, secreted frizzled
      related protein 4 (sFRP4), during renal tubular epithelial injury initiated by
      unilateral ureteral obstruction (UUO). Despite increased sFRP4 gene expression in
      perivascular regions of injured kidneys, total sFRP4 protein levels decreased
      after injury. The decreased sFRP4 protein levels after UUO accompanied increased
      Wnt-dependent beta-catenin signaling in tubular epithelial and interstitial
      cells, along with increased expression of markers of fibrosis. Administration of
      recombinant sFRP4 protein caused a reduction in tubular epithelial beta-catenin
      signaling and suppressed the progression of renal fibrosis, as evidenced by a
      partial maintenance of E-cadherin mRNA expression and a reduction in the amount
      of fibronectin and alpha-smooth muscle actin proteins. Furthermore, recombinant
      sFRP4 reduced the number of myofibroblasts, a central mediator of fibrosis. It is
      concluded that beta-catenin signaling is activated in tubular epithelial and
      interstitial cells after renal injury, and recombinant sFRP4 can interfere with
      epithelial de-differentiation and with fibroblast differentiation and function
      during progression of renal fibrosis.

PMID- 15944337
TI  - Sevelamer controls parathyroid hormone-induced bone disease as efficiently as
      calcium carbonate without increasing serum calcium levels during therapy with
      active vitamin D sterols.
AB  - Little is known about the impact of various phosphate binders on the skeletal
      lesions of secondary hyperparathyroidism (2 degrees HPT). The effects of calcium
      carbonate (CaCO3) and sevelamer were compared in pediatric peritoneal dialysis
      patients with bone biopsy-proven 2 degrees HPT. Twenty-nine patients were
      randomly assigned to CaCO3 (n = 14) or sevelamer (n = 15), concomitant with
      either intermittent doses of oral calcitriol or doxercalciferol for 8 mo, when
      bone biopsies were repeated. Serum phosphorus, calcium, parathyroid hormone
      (PTH), and alkaline phosphatase were measured monthly. The skeletal lesions of 2
      degrees HPT improved with both binders, and bone formation rates reached the
      normal range in approximately 75% of the patients. Overall, serum phosphorus
      levels were 5.5 +/- 0.1 and 5.6 +/- 0.3 mg/dl (NS) with CaCO3 and sevelamer,
      respectively. Serum calcium levels and the Ca x P ion product increased with
      CaCO3; in contrast, values remained unchanged with sevelamer (9.6 +/- 01 versus
      8.9 +/- 0.2 mg/dl; P < 0.001, respectively). Hypercalcemic episodes (>10.2 mg/dl)
      occurred more frequently with CaCO3 (P < 0.01). Baseline PTH levels were 980 +/-
      112 and 975 +/- 174 pg/ml (NS); these values decreased to 369 +/- 92 (P < 0.01)
      and 562 +/- 164 pg/ml (P < 0.01) in the CaCO3 and the sevelamer groups,
      respectively (NS between groups). Serum alkaline phosphatase levels also
      diminished in both groups (P < 0.01). Thus, treatment with either CaCO3 or
      sevelamer resulted in equivalent control of the biochemical and skeletal lesions
      of 2 degrees HPT. Sevelamer, however, maintained serum calcium concentrations
      closer to the lower end of the normal physiologic range, thereby increasing the
      safety of treatment with active vitamin D sterols.

PMID- 15944338
TI  - Peroxisome proliferator-activated receptor beta/delta exerts a strong protection
      from ischemic acute renal failure.
AB  - Ischemic acute renal failure is characterized by damages to the proximal straight
      tubule in the outer medulla. Lesions include loss of polarity, shedding into the
      tubule lumen, and eventually necrotic or apoptotic death of epithelial cells. It
      was recently shown that peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) increases keratinocyte survival after an inflammatory reaction.
      Therefore, whether PPARbeta/delta could contribute also to the control of tubular
      epithelium death after renal ischemia/reperfusion was tested. It was found that
      PPARbeta/delta+/- and PPARbeta/delta-/- mutant mice exhibited much greater kidney
      dysfunction and injury than wild-type counterparts after a 30-min renal ischemia
      followed by a 36-h reperfusion. Conversely, wild-type mice that were given the
      specific PPARbeta/delta ligand L-165041 before renal ischemia were completely
      protected against renal dysfunction, as indicated by the lack of rise in serum
      creatinine and fractional excretion of Na+. This protective effect was
      accompanied by a significant reduction in medullary necrosis, apoptosis, and
      inflammation. On the basis of in vitro studies, PPARbeta/delta ligands seem to
      exert their role by activating the antiapoptotic Akt signaling pathway and,
      unexpectedly, by increasing the spreading of tubular epithelial cells, thus
      limiting potentially their shedding and anoikis. These results point to
      PPARbeta/delta as a remarkable new target for preconditioning strategies.

PMID- 15944339
TI  - Calorie restriction modulates renal expression of sterol regulatory element
      binding proteins, lipid accumulation, and age-related renal disease.
AB  - Sterol regulatory element binding proteins (SREBP) are major regulators of fatty
      acid and cholesterol synthesis. This study found that age-related renal matrix
      deposition and proteinuria were associated with increased renal expression of
      SREBP-1 and SREBP-2 and increased renal accumulation of triglyceride and
      cholesterol. Because calorie restriction (CR) modulates age-related renal
      disease, it then was determined whether the effects of CR are mediated partially
      by modulation of renal lipid metabolism. Compared with ad libitum (AL)-fed 24
      month-old (24 m) F344BN rats, CR resulted in significant decreases in
      extracellular matrix accumulation (periodic acid-Schiff staining and
      immunofluorescence of type IV collagen and fibronectin) and proteinuria. A
      significant decrease was also observed in the renal expression of growth factors
      (connective tissue growth factor and vascular endothelial growth factor) and
      matrix metalloproteinase inhibitor (plasminogen activator inhibitor-1). These
      structural and functional changes were associated with significant decreases in
      renal nuclear SREBP-1 (5.2 in 24 m AL versus 3.3 densitometry units in 24 m CR; P
      < 0.01) and SREBP-2 (7.1 in 24 m AL versus 4.1 densitometry units in 24 m CR; P <
      0.01) protein abundance and renal triglyceride and cholesterol contents. It is
      interesting that serum leptin level was significantly increased as a function of
      aging, and CR resulted in significant reduction in serum leptin level. Because it
      was shown previously that increased renal expression of SREBP-1a per se caused
      renal lipid accumulation, glomerulosclerosis, and proteinuria, the results
      suggest that CR modulates age-related renal disease in part by modulation of
      renal SREBP expression and renal lipid accumulation.

PMID- 15944340
TI  - N-acetylcysteine decreases angiotensin II receptor binding in vascular smooth
      muscle cells.
AB  - Antioxidants seem to inhibit angiotensin II (Ang II) actions by consuming
      stimulated reactive oxygen species. An alternative hypothesis was investigated:
      Antioxidants that are also strong reducers of disulfide bonds inhibit the binding
      of Ang II to its surface receptors with consequent attenuation of signal
      transduction and cell action. Incubation of cultured vascular smooth muscle
      cells, which possess Ang II type 1a receptors, with the reducing agent n
      acetylcysteine (NAC) for 1 h at 37 degrees C resulted in decreased Ang II
      radioligand binding in a concentration-dependent pattern. NAC removal restored
      Ang II binding within 30 min. Incubation with n-acetylserine, a nonreducing
      analogue of NAC, did not lower Ang II binding, and oxidized NAC was less
      effective than reduced NAC in lowering Ang II binding. NAC did not decrease Ang
      II type 1a receptor protein content. Other antioxidants regulated Ang II
      receptors differently: alpha-Lipoic acid lowered Ang II binding after 24 h, and
      vitamin E did not lower Ang II binding at all. NAC inhibited Ang II binding in
      cell membranes at 21 or 37 but not 4 degrees C. Dihydrolipoic acid (the reduced
      form of alpha-lipoic acid), which contains free sulfhydryl groups as NAC does,
      decreased Ang II receptor binding in cell membranes, whereas alpha-lipoic acid,
      which does not contain free sulfhydryl groups, did not. Ang II-stimulated
      inositol phosphate formation was decreased by preincubation with NAC (1 h) or
      alpha-lipoic acid (24 h) but not vitamin E. In conclusion, certain antioxidants
      that are reducing agents lower Ang II receptor binding, and Ang II-stimulated
      signal transduction is decreased in proportion to decreased receptor binding.

PMID- 15944341
TI  - Glomerular expression of CD80 and CD86 is required for leukocyte accumulation and
      injury in crescentic glomerulonephritis.
AB  - The participation of renal expression of CD80 and CD86 in the immunopathogenesis
      of crescentic Th1-mediated anti-glomerular basement membrane (anti-GBM)
      glomerulonephritis (GN) has not been assessed. Immunohistochemical staining
      demonstrated prominent upregulation of both molecules in glomeruli of mice with
      anti-GBM GN, suggesting a potential role for the local expression of CD80 and
      CD86 in nephritogenic effector T cell responses. For testing this hypothesis,
      control or inhibitory anti-CD80 and/or anti-CD86 mAb were administered to mice
      during the effector phase of the disease but after the establishment of a
      systemic immune response. Anti-CD80 or anti-CD86 mAb treatment had no effect on
      the development of GN or infiltration of leukocytes into glomeruli; however,
      administration of anti-CD80/86 mAb attenuated glomerular accumulation of CD4+ T
      cells and macrophages, crescent formation, and proteinuria, correlating with
      reduced antigen-specific skin delayed-type hypersensitivity. Attenuated
      glomerular infiltration of leukocytes in mice that were treated with anti-CD80/86
      mAb was associated with decreased intraglomerular expression of adhesion
      molecules P-selectin and intercellular adhesion molecule-1, as well as attenuated
      renal mRNA levels of proinflammatory cytokines IFN-gamma and migration inhibitory
      factor, without reducing chemokine and chemokine receptor expression in the
      kidney or intraglomerular apoptosis and proliferation. The systemic Th1/Th2
      balance (assessed by splenocyte production of IFN-gamma and IL-4 and circulating
      levels of IgG1 and IgG2a) was not affected by the inhibition of CD80 and CD86.
      These studies show that CD80 and CD86 are expressed in glomeruli of mice with
      crescentic anti-GBM GN, in which they play a critical role in facilitating
      accumulation of Th1 effectors and macrophages, thus exacerbating renal injury.

PMID- 15944342
TI  - Birth weight and creatinine clearance in young adult twins: influence of genetic,
      prenatal, and maternal factors.
AB  - Previous studies have shown that low birth weight (LBW) is a risk factor for
      renal impairment in adult life. The effects of LBW and renal function were
      studied by using twins, which allows distinguishing among fetoplacental,
      maternal, and genetic influences. Perinatal data were obtained at birth, and
      absolute creatinine clearance (not corrected for body surface area) was measured
      at a mean age of 25.6 yr in 653 individuals. Twins were considered both as
      individuals and as members of twin pairs. Statistical analyses were performed
      with and without adjusting for gestational age, zygosity, gender, age, body mass
      index, glucose level, BP, and smoking status. Creatinine clearance was 4 ml/min
      lower in twins with LBW (<2500 g) than in twins with a high birth weight (P <
      0.04, adjusted). Intrapair birth weight difference correlated positively with the
      intrapair difference in creatinine clearance equally in monozygotic and dizygotic
      twins (r = 0.35, P < 0.0001; r = 0.43, P < 0.0001, respectively). This suggests
      that fetoplacental factors are related to renal function and that genetic factors
      are less important. There was no significant difference in creatinine clearance
      between twins who both had LBW as compared with twins who both had a high birth
      weight. This may suggest that maternal factors, which influence the relation
      between LBW and renal function, are less important. LBW is related to a lower
      creatinine clearance at adult age. This relationship is probably due to
      fetoplacental factors. Surprising, genetic and maternal factors seem less
      important.

PMID- 15944343
TI  - Mutational analysis of the pH signal transduction component PalC of Aspergillus
      nidulans supports distant similarity to BRO1 domain family members.
AB  - The alkaline ambient pH signal transduction pathway component PalC has no
      assigned molecular role. Therefore we attempted a gene-specific mutational
      analysis and obtained 55 new palC loss-of-function alleles including 24 single
      residue substitutions. Refined similarity searches reveal conserved PalC regions
      including one with convincing similarity to the BRO1 domain, denoted PCBROH,
      where clustering of mutational changes, including PCBROH key residue
      substitutions, supports its structural and/or functional importance. Since the
      BRO1 domain occurs in the multivesicular body (MVB) pathway protein Bro1/Vps31
      and also the pH signal transduction protein PalA (Rim20), both of which interact
      with MVB component (ESCRT-III protein) Vps32/Snf7, this might reflect a further
      link between the pH response and endocytosis.

PMID- 15944344
TI  - Systematic segregation to mutant mitochondrial DNA and accompanying loss of
      mitochondrial DNA in human NT2 teratocarcinoma Cybrids.
AB  - In this study a well-characterized pathological mutation at nucleotide position
      3243 of human mitochondrial DNA was introduced into human rho(0) teratocarcinoma
      (NT2) cells. In cloned and mixed populations of NT2 cells heteroplasmic for the
      mutation, mitotic segregation toward increasing levels of mutant mitochondrial
      DNA always occurred. Rapid segregation was frequently followed by complete loss
      of mitochondrial DNA. These findings support the idea that pathological
      mitochondrial DNA mutations are particularly deleterious in specific cell types,
      which can explain some of the tissue-specific aspects of mitochondrial DNA
      diseases. Moreover, these findings suggest that mitochondrial DNA depletion may
      be an important and widespread feature of mitochondrial DNA disease.

PMID- 15944345
TI  - Cross-species comparison of Drosophila male accessory gland protein genes.
AB  - Drosophila melanogaster males transfer seminal fluid proteins along with sperm
      during mating. Among these proteins, ACPs (Accessory gland proteins) from the
      male's accessory gland induce behavioral, physiological, and life span reduction
      in mated females and mediate sperm storage and utilization. A previous
      evolutionary EST screen in D. simulans identified partial cDNAs for 57 new
      candidate ACPs. Here we report the annotation and confirmation of the
      corresponding Acp genes in D. melanogaster. Of 57 new candidate Acp genes
      previously reported in D. melanogaster, 34 conform to our more stringent criteria
      for encoding putative male accessory gland extracellular proteins, thus bringing
      the total number of ACPs identified to 52 (34 plus 18 previously identified).
      This comprehensive set of Acp genes allows us to dissect the patterns of
      evolutionary change in a suite of proteins from a single male-specific
      reproductive tissue. We used sequence-based analysis to examine codon bias, gene
      duplications, and levels of divergence (via dN/dS values and ortholog detection)
      of the 52 D. melanogaster ACPs in D. simulans, D. yakuba, and D. pseudoobscura.
      We show that 58% of the 52 D. melanogaster Acp genes are detectable in D.
      pseudoobscura. Sequence comparisons of ACPs shared and not shared between D.
      melanogaster and D. pseudoobscura show that there are separate classes undergoing
      distinctly dissimilar evolutionary dynamics.

PMID- 15944346
TI  - Multiple roles of a heterotrimeric G-protein gamma-subunit in governing growth
      and development of Aspergillus nidulans.
AB  - Vegetative growth signaling in the filamentous fungus Aspergillus nidulans is
      primarily mediated by the heterotrimeric G-protein composed of FadA (G alpha),
      SfaD (G beta), and a presumed G gamma. Analysis of the A. nidulans genome
      identified a single gene named gpgA encoding a putative G gamma-subunit. The
      predicted GpgA protein consists of 90 amino acids showing 72% similarity with
      yeast Ste18p. Deletion (delta) of gpgA resulted in restricted vegetative growth
      and lowered asexual sporulation. Moreover, similar to the delta sfaD mutant, the
      delta gpgA mutant was unable to produce sexual fruiting bodies (cleistothecia) in
      self-fertilization and was severely impaired with cleistothecial development in
      outcross, indicating that both SfaD and GpgA are required for fruiting body
      formation. Developmental and morphological defects caused by deletion of flbA
      encoding an RGS protein negatively controlling FadA-mediated vegetative growth
      signaling were suppressed by delta gpgA, indicating that GpgA functions in FadA
      SfaD-mediated vegetative growth signaling. However, deletion of gpgA could not
      bypass the need for the early developmental activator FluG in asexual
      sporulation, suggesting that GpgA functions in a separate signaling pathway. We
      propose that GpgA is the only A. nidulans G gamma-subunit and is required for
      normal vegetative growth as well as proper asexual and sexual developmental
      progression.

PMID- 15944347
TI  - The impact of using related individuals for haplotype reconstruction in
      population studies.
AB  - Recent studies have highlighted the dangers of using haplotypes reconstructed
      directly from population data for a fine-scale mapping analysis. Family data may
      help resolve ambiguity, yet can be costly to obtain. This study is concerned with
      the following question: How much family data (if any) should be used to
      facilitate haplotype reconstruction in a population study? We conduct a
      simulation study to evaluate how changes in family information can affect the
      accuracy of haplotype frequency estimates and phase reconstruction. To
      reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently
      accommodate unrelated individuals, parent-child trios, and arbitrarily large half
      sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency
      distributions, all of which have been previously published in empirical studies.
      A wide variety of important results regarding the effectiveness of using pedigree
      data in a population study are presented in a coherent, unified framework.
      Insight into the different properties of the haplotype frequency distribution
      that can influence experimental design is provided. We show that a preliminary
      estimate of the haplotype frequency distribution can be valuable in large
      population studies with fixed resources.

PMID- 15944348
TI  - A duplication in the canine beta-galactosidase gene GLB1 causes exon skipping and
      GM1-gangliosidosis in Alaskan huskies.
AB  - GM(1)-gangliosidosis is a lysosomal storage disease that is inherited as an
      autosomal recessive disorder, predominantly caused by structural defects in the
      beta-galactosidase gene (GLB1). The molecular cause of GM(1)-gangliosidosis in
      Alaskan huskies was investigated and a novel 19-bp duplication in exon 15 of the
      GLB1 gene was identified. The duplication comprised positions +1688-+1706 of the
      GLB1 cDNA. It partially disrupted a potential exon splicing enhancer (ESE),
      leading to exon skipping in a fraction of the transcripts. Thus, the mutation
      caused the expression of two different mRNAs from the mutant allele. One
      transcript contained the complete exon 15 with the 19-bp duplication, while the
      other transcript lacked exon 15. In the transcript containing exon 15 with the 19
      bp duplication a premature termination codon (PTC) appeared, but due to its
      localization in the last exon of canine GLB1, nonsense-mediated RNA decay (NMD)
      did not occur. As a consequence of these molecular events two different truncated
      GLB1 proteins are predicted to be expressed from the mutant GLB1 allele. In
      heterozygous carrier animals the wild-type allele produces sufficient amounts of
      the active enzyme to prevent clinical signs of disease. In affected homozygous
      dogs no functional GLB1 is synthesized and G(M1)-gangliosidosis occurs.

PMID- 15944349
TI  - Construction of linkage maps in full-sib families of diploid outbreeding species
      by minimizing the number of recombinations in hidden inheritance vectors.
AB  - This article investigates the construction of linkage maps by means of the
      reconstruction of hidden inheritance vectors. An inheritance vector provides a
      description of the origin of marker alleles in an individual in terms of a binary
      code indicating the grandparental origin of the alleles. The practical
      application that is considered is the full-sib family of a diploid outbreeding
      species. Essentially, map construction is considered as an optimization problem
      in which marker data are used as restrictions on hidden inheritance vectors.
      Simulated annealing, a form of combinatorial optimization, is used to minimize
      the number of recombinations between adjacent markers. The new algorithm is
      applied to simulated data as well as to practical data obtained from a cross
      between two apple cultivars. For the practical data, a detailed procedure for
      examining the reliability of individual markers and their positions on the map is
      presented. Extensions of the method for more complicated population structures
      are discussed.

PMID- 15944350
TI  - Epistasis in monkeyflowers.
AB  - Epistasis contributes significantly to intrapopulation variation in floral
      morphology, development time, and male fitness components of Mimulus guttatus.
      This is demonstrated with a replicated line-cross experiment involving slightly
      over 7000 plants. The line-cross methodology is based on estimates for means. It
      thus has greater power than the variance partitioning approaches historically
      used to estimate epistasis within populations. The replication of the breeding
      design across many pairs of randomly extracted, inbred lines is necessary given
      the diversity of multilocus genotypes residing within an outbred deme. Male
      fitness is shown to exhibit synergistic epistasis, an accelerating decline in
      fitness with inbreeding. Synergism is a necessary, but not sufficient, condition
      for a mutational deterministic hypothesis for the evolutionary maintenance of
      sexual reproduction. Unlike male fitness measures, flower morphology and
      development time yield positive evidence of epistasis but not of synergism. The
      results for these traits suggest that epistatic effects are variable across
      genetic backgrounds or sets of interacting loci.

PMID- 15944351
TI  - End3p-mediated endocytosis is required for spore wall formation in Saccharomyces
      cerevisiae.
AB  - During sporulation in Saccharomyces cerevisiae, vesicles transported to the
      vicinity of spindle pole bodies are fused to each other to generate bilayered
      prospore membranes (PSMs). PSMs encapsulate the haploid nuclei that arise from
      the meiotic divisions and serve as platforms for spore wall deposition. Membrane
      trafficking plays an important role in supplying vesicles for these processes.
      The endocytosis-deficient mutant, end3Delta, sporulated poorly and the spores
      produced lost resistance to ether vapor, suggesting that END3-mediated
      endocytosis is important for sporulation. End3p-GFP localized to cell and spore
      peripheries in vegetative and sporulating cells and colocalized with actin
      structures. Correspondingly, the actin cytoskeleton appeared aberrant during
      sporulation in end3Delta. Analysis of meiosis in end3Delta mutants revealed that
      the meiotic divisions occurred with wild-type kinetics. Furthermore, PSMs were
      assembled normally. However, the levels of proteins required for spore wall
      synthesis and components of the spore wall layers at spores were reduced,
      indicating that end3Delta mutants are defective in spore wall synthesis. Thus,
      END3-mediated endocytosis is important for spore wall formation. Additionally,
      cytological analyses suggest that trafficking between the plasma membrane and
      PSMs is important earlier during sporulation.

PMID- 15944352
TI  - Transvection at the vestigial locus of Drosophila melanogaster.
AB  - Transvection is a phenomenon wherein gene expression is effected by the
      interaction of alleles in trans and often results in partial complementation
      between mutant alleles. Transvection is dependent upon somatic pairing between
      homologous chromosome regions and is a form of interallelic complementation that
      does not occur at the polypeptide level. In this study we demonstrated that
      transvection could occur at the vestigial (vg) locus by revealing that partial
      complementation between two vg mutant alleles could be disrupted by changing the
      genomic location of the alleles through chromosome rearrangement. If chromosome
      rearrangements affect transvection by disrupting somatic pairing, then combining
      chromosome rearrangements that restore somatic pairing should restore
      transvection. We were able to restore partial complementation in numerous
      rearrangement trans-heterozygotes, thus providing substantial evidence that the
      observed complementation at vg results from a transvection effect. Cytological
      analyses revealed this transvection effect to have a large proximal critical
      region, a feature common to other transvection effects. In the Drosophila
      interphase nucleus, paired chromosome arms are separated into distinct,
      nonoverlapping domains. We propose that if the relative position of each arm in
      the nucleus is determined by the centromere as a relic of chromosome positions
      after the last mitotic division, then a locus will be displaced to a different
      territory of the interphase nucleus relative to its nonrearranged homolog by any
      rearrangement that links that locus to a different centromere. This physical
      displacement in the nucleus hinders transvection by disrupting the somatic
      pairing of homologous chromosomes and gives rise to proximal critical regions.

PMID- 15944353
TI  - Genetic screens for enhancers of brahma reveal functional interactions between
      the BRM chromatin-remodeling complex and the delta-notch signal transduction
      pathway in Drosophila.
AB  - The Drosophila trithorax group gene brahma (brm) encodes the ATPase subunit of a
      2-MDa chromatin-remodeling complex. brm was identified in a screen for
      transcriptional activators of homeotic genes and subsequently shown to play a
      global role in transcription by RNA polymerase II. To gain insight into the
      targeting, function, and regulation of the BRM complex, we screened for mutations
      that genetically interact with a dominant-negative allele of brm (brm(K804R)). We
      first screened for dominant mutations that are lethal in combination with a
      brm(K804R) transgene under control of the brm promoter. In a distinct but related
      screen, we identified dominant mutations that modify eye defects resulting from
      expression of brm(K804R) in the eye-antennal imaginal disc. Mutations in three
      classes of genes were identified in our screens: genes encoding subunits of the
      BRM complex (brm, moira, and osa), other proteins directly involved in
      transcription (zerknullt and RpII140), and signaling molecules (Delta and vein).
      Expression of brm(K804R) in the adult sense organ precursor lineage causes
      phenotypes similar to those resulting from impaired Delta-Notch signaling. Our
      results suggest that signaling pathways may regulate the transcription of target
      genes by regulating the activity of the BRM complex.

PMID- 15944354
TI  - Genomic mapping of direct and correlated responses to long-term selection for
      rapid growth rate in mice.
AB  - Understanding the genetic architecture of traits such as growth, body
      composition, and energy balance has become a primary focus for biomedical and
      agricultural research. The objective of this study was to map QTL in a large F(2)
      (n = 1181) population resulting from an intercross between the M16 and ICR lines
      of mice. The M16 line, developed by long-term selection for 3- to 6-week weight
      gain, is larger, heavier, fatter, hyperphagic, and diabetic relative to its
      randomly selected control line of ICR origin. The F(2) population was phenotyped
      for growth and energy intake at weekly intervals from 4 to 8 weeks of age and for
      body composition and plasma levels of insulin, leptin, TNFalpha, IL6, and glucose
      at 8 weeks and was genotyped for 80 microsatellite markers. Since the F(2) was a
      cross between a selection line and its unselected control, the QTL identified
      likely represent genes that contributed to direct and correlated responses to
      long-term selection for rapid growth rate. Across all traits measured, 95 QTL
      were identified, likely representing 19 unique regions on 13 chromosomes. Four
      chromosomes (2, 6, 11, and 17) harbored loci contributing disproportionately to
      selection response. Several QTL demonstrating differential regulation of regional
      adipose deposition and age-dependent regulation of growth and energy consumption
      were identified.

PMID- 15944355
TI  - The heterotrimeric G-protein GanB(alpha)-SfaD(beta)-GpgA(gamma) is a carbon
      source sensor involved in early cAMP-dependent germination in Aspergillus
      nidulans.
AB  - The role of heterotrimeric G-proteins in cAMP-dependent germination of conidia
      was investigated in the filamentous ascomycete Aspergillus nidulans. We
      demonstrate that the G alpha-subunit GanB mediates a rapid and transient
      activation of cAMP synthesis in response to glucose during the early period of
      germination. Moreover, deletion of individual G-protein subunits resulted in
      defective trehalose mobilization and altered germination kinetics, indicating
      that GanB(alpha)-SfaD(beta)-GpgA(gamma) constitutes a functional heterotrimer and
      controls cAMP/PKA signaling in response to glucose as well as conidial
      germination. Further genetic analyses suggest that GanB plays a primary role in
      cAMP/PKA signaling, whereas the SfaD-GpgA (G betagamma) heterodimer is crucial
      for proper activation of GanB signaling sensitized by glucose. In addition, the
      RGS protein RgsA is also involved in regulation of the cAMP/PKA pathway and
      germination via attenuation of GanB signaling. Genetic epistatic analyses led us
      to conclude that all controls exerted by GanB(alpha)-SfaD(beta)-GpgA(gamma) on
      conidial germination are mediated through the cAMP/PKA pathway. Furthermore, GanB
      may function in sensing various carbon sources and subsequent activation of
      downstream signaling for germination.

PMID- 15944357
TI  - A 1927 study supports a current genetic model for inheritance of human scalp hair
      whorl orientation and hand-use preference traits.
AB  - The basis of right- vs. left-hand-use preference in humans has been debated for a
      long time. Culturally learned, birth stress, and biologically specified causes
      are the prominent etiologies under consideration. A 2003 (Klar 2003) study
      reported a correlation between a person's preferred hand and the scalp hair-whorl
      orientation developed on the head. By reinterpreting results of a 1927
      (Schwarzburg 1927) study on the genetics of the hair-whorl trait, support for a
      recent single gene, two-allele "random-recessive model" for both hair-whorl
      orientation and handedness trait inheritance is demonstrated.

PMID- 15944356
TI  - Imprinting capacity of gamete lineages in Caenorhabditis elegans.
AB  - We have observed a gamete-of-origin imprinting effect in C. elegans using a set
      of GFP reporter transgenes. From a single progenitor line carrying an
      extrachromosomal unc-54::gfp transgene array, we generated three independent
      autosomal integrations of the unc-54::gfp transgene. The progenitor line, two of
      its three integrated derivatives, and a nonrelated unc-119:gfp transgene exhibit
      an imprinting effect: single-generation transmission of these transgenes through
      the male germline results in approximately 1.5- to 2.0-fold greater expression
      than transmission through the female germline. There is a detectable resetting of
      the imprint after passage through the opposite germline for a single generation,
      indicating that the imprinted status of the transgenes is reversible. In cases
      where the transgene is maintained in either the oocyte lineage or sperm lineage
      for multiple, consecutive generations, a full reset requires passage through the
      opposite germline for several generations. Taken together, our results indicate
      that C. elegans has the ability to imprint chromosomes and that differences in
      the cell and/or molecular biology of oogenesis and spermatogenesis are manifest
      in an imprint that can persist in both somatic and germline gene expression for
      multiple generations.

PMID- 15944358
TI  - Selection for recombination in structured populations.
AB  - In finite populations, linkage disequilibria generated by the interaction of
      drift and directional selection (Hill-Robertson effect) can select for sex and
      recombination, even in the absence of epistasis. Previous models of this process
      predict very little advantage to recombination in large panmictic populations. In
      this article we demonstrate that substantial levels of linkage disequilibria can
      accumulate by drift in the presence of selection in populations of any size,
      provided that the population is subdivided. We quantify (i) the linkage
      disequilibrium produced by the interaction of drift and selection during the
      selective sweep of beneficial alleles at two loci in a subdivided population and
      (ii) the selection for recombination generated by these disequilibria. We show
      that, in a population subdivided into n demes of large size N, both the
      disequilibrium and the selection for recombination are equivalent to that
      expected in a single population of a size intermediate between the size of each
      deme (N) and the total size (nN), depending on the rate of migration among demes,
      m. We also show by simulations that, with small demes, the selection for
      recombination is stronger than both that expected in an unstructured population
      (m = 1 - 1/n) and that expected in a set of isolated demes (m = 0). Indeed,
      migration maintains polymorphisms that would otherwise be lost rapidly from small
      demes, while population structure maintains enough local stochasticity to
      generate linkage disequilibria. These effects are also strong enough to overcome
      the twofold cost of sex under strong selection when sex is initially rare.
      Overall, our results show that the stochastic theories of the evolution of sex
      apply to a much broader range of conditions than previously expected.

PMID- 15944359
TI  - Genome-wide analysis on inbreeding effects on gene expression in Drosophila
      melanogaster.
AB  - The deleterious consequences of inbreeding, especially in the form of inbreeding
      depression, are well known. However, little is known about how inbreeding affects
      genome-wide gene expression. Here, we show that inbreeding changes transcription
      levels for a number of genes. Gene expression profiles of Drosophila melanogaster
      lines inbred to F approximately = 0.67 at different rates changed relative to
      those of noninbred lines, but the rate of inbreeding did not significantly affect
      gene expression patterns. Genes being differentially expressed with inbreeding
      are disproportionately involved in metabolism and stress responses, suggesting
      that inbreeding acts like an environmental stress factor.

PMID- 15944360
TI  - Natural variation in the Pto pathogen resistance gene within species of wild
      tomato (Lycopersicon). I. Functional analysis of Pto alleles.
AB  - Disease resistance to the bacterial pathogen Pseudomonas syringae pv. tomato
      (Pst) in the cultivated tomato, Lycopersicon esculentum, and the closely related
      L. pimpinellifolium is triggered by the physical interaction between plant
      disease resistance protein, Pto, and the pathogen avirulence protein, AvrPto. To
      investigate the extent to which variation in the Pto gene is responsible for
      naturally occurring variation in resistance to Pst, we determined the resistance
      phenotype of 51 accessions from seven species of Lycopersicon to isogenic strains
      of Pst differing in the presence of avrPto. One-third of the plants displayed
      resistance specifically when the pathogen expressed AvrPto, consistent with a
      gene-for-gene interaction. To test whether this resistance in these species was
      conferred specifically by the Pto gene, alleles of Pto were amplified and
      sequenced from 49 individuals and a subset (16) of these alleles was tested in
      planta using Agrobacterium-mediated transient assays. Eleven alleles conferred a
      hypersensitive resistance response (HR) in the presence of AvrPto, while 5 did
      not. Ten amino acid substitutions associated with the absence of AvrPto
      recognition and HR were identified, none of which had been identified in previous
      structure-function studies. Additionally, 3 alleles encoding putative pseudogenes
      of Pto were isolated from two species of Lycopersicon. Therefore, a large
      proportion, but not all, of the natural variation in the reaction to strains of
      Pst expressing AvrPto can be attributed to sequence variation in the Pto gene.

PMID- 15944361
TI  - Distributions of beneficial fitness effects in RNA.
AB  - Beneficial mutations are the driving force of evolution by natural selection.
      Yet, relatively little is known about the distribution of the fitness effects of
      beneficial mutations in populations. Recent work of Gillespie and Orr suggested
      some of the first generalizations for the distributions of beneficial fitness
      effects and, surprisingly, they depend only weakly on biological details. In
      particular, the theory suggests that beneficial mutations obey an exponential
      distribution of fitness effects, with the same exponential parameter across
      different regions of genotype space, provided only that few possible beneficial
      mutations are available to that genotype. Here we tested this hypothesis with a
      quasi-empirical model of RNA evolution in which fitness is based on the secondary
      structures of molecules and their thermodynamic stabilities. The fitnesses of
      randomly selected genotypes appeared to follow a Gumbel-type distribution and
      thus conform to a basic assumption of adaptation theory. However, the observed
      distributions of beneficial fitness effects conflict with specific predictions of
      the theory. In particular, the distributions of beneficial fitness effects
      appeared exponential only when the vast majority of small-effect beneficial
      mutations were ignored. Additionally, the distribution of beneficial fitness
      effects varied with the fitness of the parent genotype. We believe that
      correlation of the fitness values among similar genotypes is likely the cause of
      the departure from the predictions of recent adaptation theory. Although in
      conflict with the current theory, these results suggest that more complex
      statistical generalizations about beneficial mutations may be possible.

PMID- 15944362
TI  - The exchangeability of amino acids in proteins.
AB  - The comparative analysis of protein sequences depends crucially on measures of
      amino acid similarity or distance. Many such measures exist, yet it is not known
      how well these measures reflect the operational exchangeability of amino acids in
      proteins, since most are derived by methods that confound a variety of effects,
      including effects of mutation. In pursuit of a pure measure of exchangeability,
      we present (1) a compilation of data on the effects of 9671 amino acid exchanges
      engineered and assayed in a set of 12 proteins; (2) a statistical procedure to
      combine results from diverse assays of exchange effects; (3) a matrix of
      "experimental exchangeability" values EX(ij) derived from applying this procedure
      to the compiled data; and (4) a set of three tests designed to evaluate the power
      of an exchangeability measure to (i) predict the effects of amino acid exchanges
      in the laboratory, (ii) account for the disease-causing potential of missense
      mutations in the human population, and (iii) model the probability of fixation of
      missense mutations in evolution. EX not only captures useful information on
      exchangeability while remaining free of other effects, but also outperforms all
      measures tested except for the best-performing alignment scoring matrix, which is
      comparable in performance.

PMID- 15944363
TI  - Aneuploidy and genetic variation in the Arabidopsis thaliana triploid response.
AB  - Polyploidy, the inheritance of more than two genome copies per cell, has played a
      major role in the evolution of higher plants. Little is known about the
      transition from diploidy to polyploidy but in some species, triploids are thought
      to function as intermediates in this transition. In contrast, in other species
      triploidy is viewed as a block. We investigated the responses of Arabidopsis
      thaliana to triploidy. The role of genetic variability was tested by comparing
      triploids generated from crosses between Col-0, a diploid, and either a natural
      autotetraploid (Wa-1) or an induced tetraploid of Col-0. In this study, we
      demonstrate that triploids of A. thaliana are fertile, producing a swarm of
      different aneuploids. Propagation of the progeny of a triploid for a few
      generations resulted in diploid and tetraploid cohorts. This demonstrated that,
      in A. thaliana, triploids can readily form tetraploids and function as bridges
      between euploid types. Genetic analysis of recombinant inbred lines produced from
      a triploid identified a locus on chromosome I exhibiting allelic bias in the
      tetraploid lines but not in the diploid lines. Thus, genetic variation was
      subject to selection contingent on the final ploidy and possibly acting during
      the protracted aneuploid phase.

PMID- 15944364
TI  - Drosophila ERCC1 is required for a subset of MEI-9-dependent meiotic crossovers.
AB  - Drosophila MEI-9 is the catalytic subunit of a DNA structure-specific
      endonuclease required for nucleotide excision repair (NER). The enzymatic
      activity of this endonuclease during NER requires the presence of a second,
      noncatalytic subunit called ERCC1. In addition to its role in NER, MEI-9 is
      required for the generation of most meiotic crossovers. To better understand the
      role of MEI-9 in crossover formation, we report here the characterization of the
      Drosophila Ercc1 gene. We created an Ercc1 mutant through homologous gene
      targeting. We find that Ercc1 mutants are identical to mei-9 mutants in
      sensitivity to DNA-damaging agents, but have a less severe reduction in the
      number of meiotic crossovers. MEI-9 protein levels are reduced in Ercc1 mutants;
      however, overexpression of MEI-9 is not sufficient to restore meiotic crossing
      over in Ercc1 mutants. We conclude that MEI-9 can generate some meiotic
      crossovers in an ERCC1-independent manner.

PMID- 15944365
TI  - Balancing selection in the wild: testing population genetics theory of self
      incompatibility in the rare species Brassica insularis.
AB  - Self-incompatibility (SI) systems are widespread mechanisms that prevent self
      fertilization in angiosperms. They are generally encoded by one genome region
      containing several multiallelic genes, usually called the S-locus. They involve a
      recognition step between the pollen and the pistil component and pollen is
      rejected when it shares alleles with the pistil. The direct consequence is that
      rare alleles are favored, such that the S-alleles are subject to negative
      frequency-dependent selection. Several theoretical articles have predicted the
      specific patterns of polymorphism, compared to neutral loci, expected for such
      genes under balancing selection. For instance, many more alleles should be
      maintained and populations should be less differentiated than for neutral loci.
      However, empirical tests of these predictions in natural populations have
      remained scarce. Here, we compare the genetic structure at the S-locus and
      microsatellite markers for five natural populations of the rare species Brassica
      insularis. As in other Brassica species, B. insularis has a sporophytic SI system
      for which molecular markers are available. Our results match well the theoretical
      predictions and constitute the first general comparison of S-allele and neutral
      polymorphism.

PMID- 15944366
TI  - Neutral evolution of the nonbinding region of the anthocyanin regulatory gene
      Ipmyb1 in Ipomoea.
AB  - Plant transcription factors often contain domains that evolve very rapidly.
      Although it has been suggested that this rapid evolution may contribute
      substantially to phenotypic differentiation among species, this suggestion has
      seldom been tested explicitly. We tested the validity of this hypothesis by
      examining the rapidly evolving non-DNA-binding region of an R2R3-myb
      transcription factor that regulates anthocyanin expression in flowers of the
      genus Ipomoea. We first provide evidence that the W locus in Ipomoea purpurea,
      which determines whether flowers will be pigmented or white, corresponds to a myb
      gene segregating in southeastern U.S. populations for one functional allele and
      one nonfunctional allele. While the binding domain exhibits substantial selective
      constraint, the nonbinding region evolves at an average K(a)/K(s) ratio of 0.74.
      This elevated rate of evolution is due to relaxed constraint rather than to
      increased levels of positive selection. Despite this relaxed constraint, however,
      approximately 20-25% of the codons, randomly distributed throughout the
      nonbinding region, are highly constrained, with the remainder evolving neutrally,
      indicating that the entire region performs important function(s). Our results
      provide little indication that rapid evolution in this regulatory gene is driven
      by natural selection or that it is responsible for floral-color differences among
      Ipomoea species.

PMID- 15944367
TI  - DNA sequence polymorphism and divergence at the erect wing and suppressor of
      sable loci of Drosophila melanogaster and D. simulans.
AB  - Several evolutionary models of linked selection (e.g., genetic hitchhiking,
      background selection, and random environment) predict a reduction in polymorphism
      relative to divergence in genomic regions where the rate of crossing over per
      physical distance is restricted. We tested this prediction near the telomere of
      the Drosophila melanogaster and D. simulans X chromosome at two loci, erect wing
      (ewg) and suppressor of sable [su(s)]. Consistent with this prediction,
      polymorphism is reduced at both loci, while divergence is normal. The reduction
      is greater at ewg, the more distal of the two regions. Two models can be
      discriminated by comparing the observed site frequency spectra with those
      predicted by the models. The hitchhiking model predicts a skew toward rare
      variants in a sample, while the spectra under the background-selection model are
      similar to those of the neutral model of molecular evolution. Statistical tests
      of the fit to the predictions of these models require many sampled alleles and
      segregating sites. Thus we used SSCP and stratified DNA sequencing to cover a
      large number of randomly sampled alleles (approximately 50) from each of three
      populations. The result is a clear trend toward negative values of Tajima's D,
      indicating an excess of rare variants at ewg, the more distal of the two loci.
      One fixed difference among the populations and high FST values indicate strong
      population subdivision among the three populations at ewg. These results indicate
      genetic hitchhiking at ewg, in particular, geographically localized hitchhiking
      events within Africa. The reduction of polymorphism at su(s) combined with the
      excess of high-frequency variants in D. simulans is inconsistent with the
      hitchhiking and background-selection models.

PMID- 15944368
TI  - Polygenic mutation in Drosophila melanogaster: Mapping spontaneous mutations
      affecting sensory bristle number.
AB  - Our ability to predict long-term responses to artificial and natural selection,
      and understand the mechanisms by which naturally occurring variation for
      quantitative traits is maintained, depends on detailed knowledge of the
      properties of spontaneous polygenic mutations, including the quantitative trait
      loci (QTL) at which mutations occur, mutation rates, and mutational effects.
      These parameters can be estimated by mapping QTL that cause divergence between
      mutation-accumulation lines that have been established from an inbred base
      population and selected for high and low trait values. Here, we have utilized
      quantitative complementation to deficiencies to map QTL at which spontaneous
      mutations affecting Drosophila abdominal and sternopleural bristle number have
      occurred in 11 replicate lines during 206 generations of divergent selection.
      Estimates of the numbers of mutations were consistent with diploid per-character
      mutation rates for bristle traits of 0.03. The ratio of the per-character
      mutation rate to total mutation rate (0.023) implies that >2% of the genome could
      affect just one bristle trait and that there must be extensive pleiotropy for
      quantitative phenotypes. The estimated mutational effects were not, however,
      additive and exhibited dependency on genetic background consistent with
      diminishing epistasis. However, these inferences must be tempered by the
      potential for epistatic interactions between spontaneous mutations and QTL
      affecting bristle number on the deficiency-bearing chromosomes, which could lead
      to overestimates in numbers of QTL and inaccurate inference of gene action.

PMID- 15944369
TI  - Adding confidence to gene expression clustering.
AB  - It has been well established that gene expression data contain large amounts of
      random variation that affects both the analysis and the results of microarray
      experiments. Typically, microarray data are either tested for differential
      expression between conditions or grouped on the basis of profiles that are
      assessed temporally or across genetic or environmental conditions. While testing
      differential expression relies on levels of certainty to evaluate the relative
      worth of various analyses, cluster analysis is exploratory in nature and has not
      had the benefit of any judgment of statistical inference. By using a novel
      dissimilarity function to ascertain gene expression clusters and conditional
      randomization of the data space to illuminate distinctions between statistically
      significant clusters of gene expression patterns, we aim to provide a level of
      confidence to inferred clusters of gene expression data. We apply both
      permutation and convex hull approaches for randomization of the data space and
      show that both methods can provide an effective assessment of gene expression
      profiles whose coregulation is statistically different from that expected by
      random chance alone.

PMID- 15944370
TI  - Two distinct neural mechanisms for category-selective responses.
AB  - The cognitive and neural mechanisms mediating category-selective responses in the
      human brain remain controversial. Using functional magnetic resonance imaging and
      effective connectivity analyses (Dynamic Causal Modelling), we investigated
      animal- and tool-selective responses by manipulating stimulus modality (pictures
      versus words) and task (implicit versus explicit semantic). We dissociated two
      distinct mechanisms that engender category selectivity: in the ventral occipito
      temporal cortex, tool-selective responses were observed irrespective of task,
      greater for pictures and mediated by bottom-up effects. In a left temporo
      parietal action system, tool-selective responses were observed irrespective of
      modality, greater for explicit semantic tasks and mediated by top-down modulation
      from the left prefrontal cortex. These distinct activation and connectivity
      patterns suggest that the two systems support different cognitive operations,
      with the ventral occipito-temporal regions engaged in structural processing and
      the dorsal visuo-motor system in strategic semantic processing. Consistent with
      current semantic theories, explicit semantic processing of tools might thus rely
      on reactivating their associated action representations via top-down modulation.
      In terms of neuronal mechanisms, the category selectivity may be mediated by
      distinct top-down (task-dependent) and bottom-up (stimulus-dependent) mechanisms.

PMID- 15944371
TI  - Hierarchical development of the primate visual cortex, as revealed by
      neurofilament immunoreactivity: early maturation of the middle temporal area
      (MT).
AB  - It has been suggested that the development of the cerebral cortex reflects its
      hierarchical organization, with the primary sensory areas being the first to
      reach structural and functional maturity, and higher-order association areas
      being the last. In the present study, we labelled the cortex of New World
      marmoset monkeys of late fetal and early postnatal ages with an antibody to non
      phosphorylated neurofilament, a marker of structural maturation of a subset of
      pyramidal cells. Supporting the concept of hierarchical maturation, we found that
      at birth labelled cells were found in the primary visual, auditory and
      somatosensory areas, but not in most other cortical fields. The exception was
      visual area MT, which revealed an infragranular pattern of labelling comparable
      to the one observed in the primary areas, as well as some supragranular staining.
      In MT, an adult-like pattern of labelled cells, including both supragranular and
      infragranular layer neurons, emerged within the first postnatal month. In
      comparison, the development of other extrastriate areas was delayed, with the
      first signs of neurofilament staining not present until the third week. The
      present results support the concept of MT as another primary visual area, an idea
      previously advanced on the basis of functional and anatomical evidence.

PMID- 15944372
TI  - Developmental and regional expression of heparan sulfate sulfotransferase genes
      in the mouse brain.
AB  - Heparan sulfate (HS) binds with various proteins including growth factors,
      morphogens, and extracellular matrix molecules to regulate their biological
      functions. These regulatory interactions are considered to be dependent on the
      structure of HS, which is determined by HS sulfotransferases. To gain insights
      into the functions of HS sulfotransferases in the development of the nervous
      system, we examined the expression of these enzymes (3-O-sulfotransferase-1 [3
      OST-1], -2, -4; 6-OST-1, -2, -3; and N-deacetylase /N-sulfotransferase-1 [NDST
      1], -2, -3) by in situ hybridization and real-time reverse transcription
      polymerase chain reaction (RT-PCR). The expression of these genes was
      spatiotemporally regulated. In the E16 cerebrum, the expression of these genes
      showed two patterns: (1) selective expression at cortical plate (CP) and
      ventricular zone (VZ) and (2) wider expression by the cells in the marginal zone
      (MZ), CP, subplate (SP), and VZ. At P1, most genes showed similar expression
      patterns, but after P7, these genes were expressed differentially in a layer
      specific manner. In the P1 cerebellum, the external granule cell layer (EGL)
      expressed most genes, the expressions of which were down-regulated at P7. In
      contrast, Purkinje cells began to express many of these genes after P7. These
      complex expression patterns suggest that the structure of HS is altered
      spatiotemporally for regulating various biological activities in the developing
      brain including the proliferation of neuronal progenitors, extension of axons,
      and formation of dendrites. We discuss possible functional roles of these
      sulfotransferases in the signaling of several HS-binding proteins such as
      fibroblast growth factors, slit, netrin, and sonic hedgehog.

PMID- 15944373
TI  - Crystal structure of banana lectin reveals a novel second sugar binding site.
AB  - Banana lectin (Banlec) is a dimeric plant lectin from the jacalin-related lectin
      family. Banlec belongs to a subgroup of this family that binds to
      glucose/mannose, but is unique in recognizing internal alpha1,3 linkages as well
      as beta1,3 linkages at the reducing termini. Here we present the crystal
      structures of Banlec alone and with laminaribiose (LAM) (Glcbeta1, 3Glc) and Xyl
      beta1,3-Man-alpha-O-Methyl. The structure of Banlec has a beta-prism-I fold,
      similar to other family members, but differs from them in its mode of sugar
      binding. The reducing unit of the sugar is inserted into the binding site causing
      the second saccharide unit to be placed in the opposite orientation compared with
      the other ligand-bound structures of family members. More importantly, our
      structures reveal the presence of a second sugar binding site that has not been
      previously reported in the literature. The residues involved in the second site
      are common to other lectins in this family, potentially signaling a new group of
      mannose-specific jacalin-related lectins (mJRL) with two sugar binding sites.

PMID- 15944374
TI  - Urotensin II modulates rapid eye movement sleep through activation of brainstem
      cholinergic neurons.
AB  - Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity
      in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in
      particular in cholinergic neurons located in the mesopontine tegmental area,
      including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental
      nuclei. This distribution suggests that the UII system is involved in functions
      regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the
      hypothesis that UII influences cholinergic PPT neuron activity and alters rapid
      eye movement (REM) sleep patterns in rats. Local administration of UII into the
      PPT nucleus increases REM sleep without inducing changes in the cortical blood
      flow. Intracerebroventricular injection of UII enhances both REM sleep and
      wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not
      local, administration of UII increases cortical blood flow. Moreover, whole-cell
      recordings from rat-brain slices show that UII selectively excites cholinergic
      PPT neurons via an inward current and membrane depolarization that were
      accompanied by membrane conductance decreases. This effect does not depend on
      action potential generation or fast synaptic transmission because it persisted in
      the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine
      receptors. Collectively, these results suggest that UII plays a role in the
      regulation of REM sleep independently of its cerebrovascular actions by directly
      activating cholinergic brainstem neurons.

PMID- 15944375
TI  - Cortical sites critical for speech discrimination in normal and impaired
      listeners.
AB  - We used statistical modeling to investigate variability in the cortical auditory
      representations of 24 normal-hearing epilepsy patients undergoing electrocortical
      stimulation mapping (ESM). Patients were identified as normal or impaired
      listeners based on recognition accuracy for acoustically filtered words used to
      simulate everyday listening conditions. The experimental ESM task was a binary
      (same-different) auditory syllable discrimination paradigm that both listener
      groups performed accurately at baseline. Template mixture modeling of speech
      discrimination deficits during ESM showed larger and more variable cortical
      distributions for impaired listeners than normal listeners, despite comparable
      behavioral performances. These results demonstrate that individual differences in
      speech recognition abilities are reflected in the underlying cortical
      representations.

PMID- 15944376
TI  - Differential response of Period 1 expression within the suprachiasmatic nucleus.
AB  - The suprachiasmatic nuclei (SCNs) of the hypothalamus contain a circadian clock
      that exerts profound control over rhythmic physiology and behavior. The clock
      consists of multiple autonomous cellular pacemakers distributed throughout the
      rat SCN. In response to a shift in the light schedule, the SCN rapidly changes
      phase to achieve the appropriate phase relationship with the shifted light
      schedule. Through use of a transgenic rat in which rhythmicity in transcription
      of the Period 1 gene was measured with a luciferase reporter (Per1-luc), we have
      been successful in tracking the time course of molecular rhythm phase
      readjustments in different regions of the SCN that occur in response to a shift
      in the light schedule. We find that different regions of the SCN phase adjust at
      different rates, leading to transient internal desynchrony in Per1-luc expression
      among SCN regions. This desynchrony among regions is most pronounced and
      prolonged when the light schedule is advanced compared with light schedule
      delays. A similar asymmetry in the speed of phase resetting is observed with
      locomotor behavior, suggesting that phase shifting kinetics within the SCN may
      underlay the differences observed in behavioral resetting to advances or delays
      in the light schedule.

PMID- 15944377
TI  - Serotonin 5-HT1A receptors regulate NMDA receptor channels through a microtubule
      dependent mechanism.
AB  - The serotonin system and NMDA receptors (NMDARs) in prefrontal cortex (PFC) are
      both critically involved in the regulation of cognition and emotion under normal
      and pathological conditions; however, the interactions between them are
      essentially unknown. Here we show that serotonin, by activating 5-HT(1A)
      receptors, inhibited NMDA receptor-mediated ionic and synaptic currents in PFC
      pyramidal neurons, and the NR2B subunit-containing NMDA receptor is the primary
      target of 5-HT(1A) receptors. This effect of 5-HT(1A) receptors was blocked by
      agents that interfere with microtubule assembly, as well as by cellular knock
      down of the kinesin motor protein KIF17 (kinesin superfamily member 17), which
      transports NR2B-containing vesicles along microtubule in neuronal dendrites.
      Inhibition of either CaMKII (calcium/calmodulin-dependent kinase II) or MEK/ERK
      (mitogen-activated protein kinase kinase/extracellular signal-regulated kinase)
      abolished the 5-HT(1A) modulation of NMDAR currents. Biochemical evidence also
      indicates that 5-HT(1A) activation reduced microtubule stability, which was
      abolished by CaMKII or MEK inhibitors. Moreover, immunocytochemical studies show
      that 5-HT(1A) activation decreased the number of surface NR2B subunits on
      dendrites, which was prevented by the microtubule stabilizer. Together, these
      results suggest that serotonin suppresses NMDAR function through a mechanism
      dependent on microtubule/kinesin-based dendritic transport of NMDA receptors that
      is regulated by CaMKII and ERK signaling pathways. The 5-HT(1A)-NMDAR interaction
      provides a potential mechanism underlying the role of serotonin in controlling
      emotional and cognitive processes subserved by PFC.

PMID- 15944378
TI  - Calcium increases in retinal glial cells evoked by light-induced neuronal
      activity.
AB  - Electrical stimulation of neurons in brain slices evokes increases in cytoplasmic
      Ca(2+) in neighboring astrocytes. The present study tests whether similar neuron
      to-glial signaling occurs in the isolated rat retina in response to light
      stimulation. Results demonstrate that Muller cells, the principal retinal glial
      cells, generate transient increases in Ca(2+) under constant illumination. A
      flickering light stimulus increases the occurrence of these Ca(2+) transients.
      Antidromic activation of ganglion cell axons also increases the generation of
      Muller cell Ca(2+) transients. The increases in Ca(2+) transients evoked by light
      and antidromic stimulation are blocked by the purinergic antagonist suramin and
      by TTX. The addition of adenosine greatly potentiates the response to light, with
      light ON evoking large Ca(2+) increases in Muller cells. Suramin, apyrase (an ATP
      hydrolyzing enzyme), and TTX substantially reduce the adenosine-potentiated
      response. NMDA, metabotropic glutamate, GABA(B), and muscarinic receptor
      antagonists, in contrast, are mainly ineffective in blocking the response. Light
      evoked Ca(2+) responses begin in Muller cell processes within the inner plexiform
      (synaptic) layer of the retina and then spread into cell endfeet at the inner
      retinal surface. These results represent the first demonstration that Ca(2+)
      increases in CNS glia can be evoked by a natural stimulus (light flashes). The
      results suggest that neuron-to-glia signaling in the retina is mediated by
      neuronal release of ATP, most likely from amacrine and/or ganglion cells, and
      that the response is augmented under pathological conditions when adenosine
      levels increase.

PMID- 15944379
TI  - Status epilepticus increases the intracellular accumulation of GABAA receptors.
AB  - Status epilepticus is a neurological emergency that results in mortality and
      neurological morbidity. It has been postulated that the reduction of inhibitory
      transmission during status epilepticus results from a rapid modification of
      GABA(A) receptors. However, the mechanism(s) that contributes to this
      modification has not been elucidated. We report, using an in vitro model of
      status epilepticus combined with electrophysiological and cellular imaging
      techniques, that prolonged epileptiform bursting results in a reduction of GABA
      mediated synaptic inhibition. Furthermore, we found that constitutive
      internalization of GABA(A) receptors is rapid and accelerated by the increased
      neuronal activity associated with seizures. Inhibition of neuronal activity
      reduced the rate of internalization. These findings suggest that the rate of
      GABA(A) receptor internalization is regulated by neuronal activity and its
      acceleration contributes to the reduction of inhibitory transmission observed
      during prolonged seizures.

PMID- 15944381
TI  - Physiological regulation of the beta-amyloid precursor protein signaling domain
      by c-Jun N-terminal kinase JNK3 during neuronal differentiation.
AB  - Beta-amyloid precursor protein (APP) is a conserved and ubiquitous transmembrane
      glycoprotein strongly implicated in the pathogenesis of Alzheimer's disease but
      whose normal biological function is unknown. Analogy to the Notch protein
      suggests that APP is a cell-surface receptor that signals via sequential
      proteolytic cleavages that release its intracellular domain (AICD) to the
      nucleus. Because these cleavages are major targets for therapeutic inhibition, it
      is critical to elucidate their physiological function. AICD is stabilized by
      Fe65, interacts with the transcriptional factor Tip60, and translocates to the
      nucleus. Here, we show that endogenous AICD in primary neurons is detectable only
      during a short period of time during differentiation in culture. During this
      transient rise, a portion of AICD localizes to the nucleus. Subsequently,
      phosphorylation of the APP cytoplasmic domain at threonine 668 appears to disrupt
      the stabilizing interaction with Fe65 and thus downregulate AICD-mediated
      signaling. Furthermore, we find that the neuron-specific c-Jun N-terminal kinase
      JNK3, but not JNK1 or JNK2, mediates a substantial portion of this
      phosphorylation. We conclude that endogenous AICD undergoes tight temporal
      regulation during the differentiation of neurons and is negatively regulated by
      JNK3 via phosphorylation of APP at Thr668.

PMID- 15944380
TI  - Feedback and feedforward control of frequency tuning to naturalistic stimuli.
AB  - Sensory neurons must respond to a wide variety of natural stimuli that can have
      very different spatiotemporal characteristics. Optimal responsiveness to subsets
      of these stimuli can be achieved by devoting specialized neural circuitry to
      different stimulus categories, or, alternatively, this circuitry can be modulated
      or tuned to optimize responsiveness to current stimulus conditions. This study
      explores the mechanisms that enable neurons within the initial processing station
      of the electrosensory system of weakly electric fish to shift their tuning
      properties based on the spatial extent of the stimulus. These neurons are tuned
      to low frequencies when the stimulus is restricted to a small region within the
      receptive field center but are tuned to higher frequencies when the stimulus
      impinges on large regions of the sensory epithelium. Through a combination of
      modeling and in vivo electrophysiology, we reveal the respective contributions of
      the filtering characteristics of extended dendritic structures and feedback
      circuitry to this shift in tuning. Our results show that low-frequency tuning can
      result from the cable properties of an extended dendrite that conveys receptor
      afferent information to the cell body. The shift from low- to high-frequency
      tuning, seen in response to spatially extensive stimuli, results from increased
      wide-band input attributable to activation of larger populations of receptor
      afferents, as well as the activation of parallel fiber feedback from the
      cerebellum. This feedback provides a cancellation signal with low-pass
      characteristics that selectively attenuates low-frequency responsiveness. Thus,
      with spatially extensive stimuli, these cells preferentially respond to the
      higher-frequency components of the receptor-afferent input.

PMID- 15944382
TI  - Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion
      formation in SH-SY5Y cells.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      selective loss of dopaminergic neurons and the presence of Lewy bodies. Previous
      reports have shown that alpha-synuclein deposited in brain tissue from
      individuals with synucleinopathy is extensively phosphorylated at Ser-129. Here,
      we investigate the role of phosphorylation of alpha-synuclein in the formation of
      inclusions involving synphilin-1 and parkin using site-directed mutagenesis to
      change Ser-129 of alpha-synuclein to alanine (S129A) to abolish phosphorylation
      at this site. Coexpression of wild-type alpha-synuclein and synphilin-1 in human
      neuroblastoma SH-SY5Y cells yielded cytoplasmic eosinophilic inclusions with some
      features resembling Lewy bodies, whereas coexpression of S129A alpha-synuclein
      and synphlin-1 formed few or no inclusions. Moreover, coexpression of parkin with
      alpha-synuclein and synphilin-1 formed more ubiquitinated inclusions, but these
      inclusions decreased with expression of S129A alpha-synuclein instead of wild
      type alpha-synuclein. Coimmunoprecipitation assays revealed a decreased
      interaction of S129A alpha-synuclein with synphilin-1 compared with wild-type
      alpha-synuclein. Expression of S129A alpha-synuclein instead of wild-type alpha
      synuclein also decreased the association of synphilin-1 and parkin and
      subsequently reduced the parkin-mediated ubiquitination of synphilin-1 and the
      formation of ubiquitinated inclusions. Treatment of SH-SY5Y cells with H(2)O(2)
      increased alpha-synuclein phosphorylation and enhanced the formation of
      inclusions formed by coexpression of alpha-synuclein, synphilin-1, and parkin,
      whereas treatment with the casein kinase 2 inhibitor 5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole had the opposite affect. These results indicate that
      phosphorylation of alpha-synuclein at S129 may be important for the formation of
      inclusions in PD and related alpha synucleinopathies.

PMID- 15944383
TI  - Regulation of drug reward by cAMP response element-binding protein: evidence for
      two functionally distinct subregions of the ventral tegmental area.
AB  - The transcription factor cAMP response element binding protein (CREB) is
      implicated in the actions of drugs of abuse in several brain areas, but little
      information is available about a role for CREB in the ventral tegmental area
      (VTA), one of the key reward regions of the brain. Here, we demonstrate that
      chronic exposure to drugs of abuse induces CREB activity throughout the VTA.
      Using viral-mediated gene transfer, we expressed green fluorescent protein (GFP)
      tagged CREB or mCREB (a dominant-negative form of CREB) in the VTA and, using a
      conditioned place-preference paradigm, found that CREB activation within the
      rostral versus caudal subregions of the VTA produces opposite effects on drug
      reward. We identified VTA subregion-specific differences in the proportion of
      dopaminergic and GABAergic neurons and in the dopaminergic projections to the
      nucleus accumbens, another brain region implicated in drug reward, and suggest
      that this may contribute to behavioral differences in this study. We also
      measured expression levels of tyrosine hydroxylase and the AMPA glutamate
      receptor subunit GluR1, both of which are known to contribute to drug reward in
      the VTA, and found that both of these genes are upregulated following the
      expression of CREB-GFP and downregulated following expression of mCREB-GFP,
      raising the possibility that CREB may exert its effects on drug reward, in part,
      via regulation of these genes. These results suggest a novel role for CREB in
      mediating drug-induced plasticity in the VTA and establish two functionally
      distinct subregions of the VTA in which CREB differentially regulates drug
      reward.

PMID- 15944385
TI  - Regulation of microtubule severing by katanin subunits during neuronal
      development.
AB  - Katanin, the microtubule-severing protein, consists of a subunit termed P60 that
      breaks the lattice of the microtubule and another subunit termed P80, the
      functions of which are not well understood. Data presented here show that the
      ratio of P60 to P80 varies markedly in different tissues, at different phases of
      development, and regionally within the neuron. P80 is more concentrated in the
      cell body and less variable during development, whereas P60 often shows
      concentrations in the distal tips of processes as well as dramatic spikes in
      expression at certain developmental stages. Overexpression of P60 at various
      stages in the differentiation of cultured hippocampal neurons results in
      substantial loss of microtubule mass and a diminution in total process length. In
      comparison, overexpression of P80, which is thought to augment the severing of
      microtubules by P60, results in a milder loss of microtubule mass and diminution
      in process length. At the developmental stage corresponding to axogenesis,
      overexpression of P60 decreases the total number of processes extended by the
      neuron, whereas overexpression of P80 produces the opposite result, suggesting
      that the effects on neuronal morphology are dependent on the degree of
      microtubule severing and loss of polymer. The microtubules that occupy the axon
      are notably more resistant to depolymerization in response to excess P60 or P80
      than microtubules elsewhere in the neuron, suggesting that regional differences
      in the susceptibility of microtubules to severing proteins may be a critical
      factor in the generation and maintenance of neuronal polarity.

PMID- 15944384
TI  - Chronic nicotine exposure upregulates nicotinic receptors by a novel mechanism.
AB  - Nicotine addiction is initiated by its binding to high-affinity nicotinic
      receptors in brain composed primarily of alpha4 and beta2 subunits. For nicotinic
      receptors expressed in vivo or heterologously, nicotine exposure over hours to
      days increases or "upregulates" high-affinity nicotine binding to receptors
      through a posttranslational mechanism thought to increase receptor numbers. Using
      heterologous expression, we find nicotine exposure causes a fourfold to sixfold
      higher binding to alpha4beta2 receptors that does not correspond with any
      significant change in the number of surface receptors or a change in the
      assembly, trafficking, or cell-surface turnover of the receptors. However,
      upregulation does alter the functional state of the receptor, slowing
      desensitization and enhancing sensitivity to acetylcholine. Based on these
      findings, we propose an alternative mechanism to explain nicotine-induced
      upregulation in which nicotine exposure slowly stabilizes alpha4beta2 receptors
      in a high-affinity state that is more easily activated, thereby providing a
      memory for nicotine exposure.

PMID- 15944386
TI  - Neurofibromin regulates neural stem cell proliferation, survival, and astroglial
      differentiation in vitro and in vivo.
AB  - Neurofibromatosis 1 (NF1) is a common inherited disease in which affected
      children exhibit abnormalities in astrocyte growth regulation and are prone to
      the development of brain tumors (astrocytoma). Previous studies from our
      laboratory demonstrated that Nf1 mutant mouse astrocytomas contains populations
      of proliferating nestin+ progenitor cells, suggesting that immature astroglial
      progenitors may serve as a reservoir of proliferating tumor cells. Here, we
      directly examined the consequences of Nf1 inactivation on neural stem cell (NSC)
      proliferation in vitro and in vivo. We found dose-dependent effects of
      neurofibromin expression on NSC proliferation and survival in vitro, which
      reflected increased RAS pathway activation and increased bcl2 expression. In
      addition, unlike wild-type NSCs, Nf1-/- NSCs and, to a lesser extent, Nf1+/- NSCs
      survive as xenografts in naive recipient brains in vivo. Although Nf1-/- NSCs are
      multipotent, Nf1-/- and Nf1+/-, but not wild-type, NSCs generated increased
      numbers of morphologically abnormal, immature astroglial cells in vitro.
      Moreover, the Nf1-/- NSC growth and survival advantage as well as the astroglial
      cell differentiation defect were completely rescued by expression of the GAP (RAS
      GTPase activating protein) domain of neurofibromin. Finally, the increase in
      astroglial progenitors and proliferating cells seen in vitro was also observed in
      Nf1-/- and Nf1+/- embryonic as well as Nf1+/- adult brains in vivo. Collectively,
      these findings support the hypothesis that alterations in neurofibromin
      expression in the developing brain have significant consequences for astrocyte
      growth and differentiation relevant to normal brain development and astrocytoma
      formation in children.

PMID- 15944387
TI  - Phosphorylation of c-Jun in avian and mammalian motoneurons in vivo during
      programmed cell death: an early reversible event in the apoptotic cascade.
AB  - c-Jun is a transcription factor that is involved in various cellular events,
      including apoptotic cell death. For example, phosphorylation of c-Jun is one of
      the earliest biochemical changes detected in dying sympathetic neurons after NGF
      deprivation in vitro. However, currently, it is not known whether a similar
      molecular event is involved in the developmental programmed cell death (PCD) of
      neurons in vivo. We observed that only a subpopulation of motoneurons (MNs)
      exhibit c-Jun phosphorylation during the PCD period in chick [embryonic day 5
      (E5)-E12] and mouse (E13-E18) embryos. Experimental perturbation of MN survival
      promoting signals by limb bud removal (reduced signals) or by activity blockade
      (increased signals) in the chick embryo demonstrated that the presence of those
      signals is negatively correlated with the number of c-Jun-phosphorylated MNs.
      This suggests that insufficient survival signals (e.g., neurotrophic factors) may
      induce c-Jun phosphorylation of MNs in vivo. Consistent with the idea that c-Jun
      phosphorylation is a reversible event during normal PCD of MNs, we found that c
      Jun phosphorylation was transiently observed in a subpopulation of mouse MNs
      rescued from PCD by deletion of the proapoptotic gene Bax. Inhibition of c-Jun
      signaling significantly reduced MN death in chick embryo, indicating that
      activation of c-Jun signaling is necessary for the PCD of MNs. Together, c-Jun
      phosphorylation appears to be required for the initiation of an early and
      reversible event in the intracellular PCD cascade in vivo after loss of survival
      promoting signals such as neurotrophic factors.

PMID- 15944388
TI  - Bidirectional regulation of cytoplasmic polyadenylation element-binding protein
      phosphorylation by Ca2+/calmodulin-dependent protein kinase II and protein
      phosphatase 1 during hippocampal long-term potentiation.
AB  - Induction of hippocampal long-term potentiation (LTP) requires activation of
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), whereas maintenance of
      LTP additionally requires protein synthesis. We recently reported that CaMKII
      stimulates protein synthesis in depolarized hippocampal neurons through
      phosphorylation of the mRNA translation factor cytoplasmic polyadenylation
      element-binding protein (CPEB), and this phosphorylation is rapidly reversed by
      protein phosphatase 1 (PP1). Protein synthesis-dependent late-phase LTP (L-LTP)
      in the hippocampus requires calcium influx through the NMDA-type glutamate
      receptor (NMDA-R) to activate CaMKII as well as concomitant inhibition of PP1
      mediated by protein kinase A. Therefore, we investigated the regulation of CPEB
      phosphorylation during L-LTP. Pharmacological stimulation of the NMDA-R in
      hippocampal slices to produce chemical long-term depression induced a brief
      dephosphorylation of CPEB. Modest LTP induction (once at 100 Hz), which induces a
      protein synthesis-independent early-phase LTP (E-LTP), resulted in a transient
      phosphorylation of CPEB. However, stronger stimulation (four times at 100 Hz),
      known to induce protein synthesis-dependent L-LTP, elicited a prolonged
      phosphorylation of CPEB. Furthermore, CPEB phosphorylation correlated with
      phosphorylation of PP1 inhibitor dopamine- and cAMP-regulated phosphoprotein, a
      known substrate for protein kinase A. These results evoke the hypothesis that
      bidirectional regulation of CPEB phosphorylation by CaMKII and protein
      phosphatases may serve as a mechanism to convert E-LTP into protein synthesis
      dependent L-LTP by stimulating protein synthesis and thereby stabilizing synaptic
      enhancement.

PMID- 15944389
TI  - Axodendritic contacts onto calcium/calmodulin-dependent protein kinase type II
      expressing neurons in the barn owl auditory space map.
AB  - In the owl midbrain, a map of auditory space is synthesized in the inferior
      colliculus (IC) and conveyed to the optic tectum (OT). Ascending auditory
      information courses through these structures via topographic axonal projections.
      Little is known about the molecular composition of projection neurons or their
      postsynaptic targets. To visualize axodendritic contacts between identified cell
      types, we used double-label immunohistochemistry, in vivo retrograde tracing, in
      vitro anterograde tracing, high-resolution confocal microscopy, three-dimensional
      reconstruction and fly-through visualization. We discovered a major class of IC
      neurons that strongly expressed calcium/calmodulin-dependent protein kinase type
      II, alpha subunit (CaMKII). The distribution of these cells within the IC was
      mostly restricted to the external nucleus of the IC (ICX), in which the auditory
      space map is assembled. A large proportion of ICX-OT projection neurons were
      CaMKII positive. In addition to being the principal outputs, CaMKII cells were in
      direct contact with axonal boutons emanating from the main source of input to
      ICX, the lateral shell of the central nucleus of the inferior colliculus (ICCls).
      Numerous sites of putative synaptic contact were found on the somata, proximal
      dendrites, and distal dendrites. Double-label immunoelectron microscopy confirmed
      the existence of synapses between ICCls axons and the dendrites of CaMKII cells.
      Collectively, our data indicate that CaMKII ICX neurons are a cellular locus for
      the computation of auditory space-specific responses. Because the ICCls-ICX
      projection is physically altered during experience-dependent plasticity, these
      results lay the groundwork for probing microanatomical rearrangements that may
      underlie plasticity and learning.

PMID- 15944390
TI  - Synaptic facilitation and behavioral dishabituation in Aplysia: dependence on
      release of Ca2+ from postsynaptic intracellular stores, postsynaptic exocytosis,
      and modulation of postsynaptic AMPA receptor efficacy.
AB  - Sensitization and dishabituation of the defensive withdrawal reflex in Aplysia
      have been ascribed to presynaptic mechanisms, particularly presynaptic
      facilitation of transmission at sensorimotor synapses in the CNS of Aplysia.
      Here, we show that facilitation of sensorimotor synapses in cell culture during
      and after serotonin (5-HT) exposure depends on a rise in postsynaptic
      intracellular Ca(2+) and release of Ca(2+) from postsynaptic stores. We also
      provide support for the idea that postsynaptic AMPA receptor insertion mediates a
      component of synaptic facilitation by showing that facilitation after 5-HT offset
      is blocked by injecting botulinum toxin, an exocytotic inhibitor, into motor
      neurons before application of 5-HT. Using a reduced preparation, we extend our
      results to synaptic facilitation in the abdominal ganglion. We show that tail
      nerve shock-induced facilitation of siphon sensorimotor synapses also depends on
      elevated postsynaptic Ca(2+) and release of Ca(2+) from postsynaptic stores and
      recruits a late phase of facilitation that involves selective enhancement of the
      AMPA receptor-mediated synaptic response. To examine the potential role of
      postsynaptic exocytosis of AMPA receptors in learning in Aplysia, we test the
      effect of injecting botulinum toxin into siphon motor neurons on dishabituation
      of the siphon-withdrawal reflex. We find that postsynaptic injections of the
      toxin block dishabituation resulting from tail shock. Our results indicate that
      postsynaptic mechanisms, particularly Ca(2+)-dependent modulation of AMPA
      receptor trafficking, play a critical role in synaptic facilitation as well as in
      dishabituation and sensitization in Aplysia.

PMID- 15944391
TI  - Effects of Bax gene deletion on muscle and motoneuron degeneration in a sexually
      dimorphic neuromuscular system.
AB  - Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target
      muscles in the perineum, bulbocavernosus (BC), and levator ani (LA) normally
      degenerate in female rodents. Death of the motoneurons and muscles can be
      prevented by androgen treatments around the time of birth. To identify the
      intracellular mechanisms underlying hormone-dependent survival of this
      neuromuscular system, we examined mice with a targeted disruption of the pro
      death gene Bax. SNB motoneuron number was increased in female Bax-/- mice,
      whether measured using immunolabeling for a motoneuron-specific marker or
      retrograde labeling with the fluorescent tracer Fluoro-Gold. Based on retrograde
      tracing, the sex difference in SNB cell number is eliminated in Bax-/- mice.
      Thus, Bax is required for sexually dimorphic motoneuron death in the SNB, and
      motoneurons rescued by Bax deletion project their axons to the periphery. Mean
      soma size in the SNB of Bax-/- females is reduced, however, and there is a
      subpopulation of very small cells in the SNB of female knock-outs. In addition,
      the BC muscle was not identified in any female, regardless of Bax gene status.
      All females possessed a small LA muscle, and Bax deletion resulted in a tripling
      of LA fiber number in females. This increase was small, however, relative to the
      >50-fold sex difference in LA muscle fiber number. Thus, the sex difference in
      the perineal muscles is mostly unaffected by the absence of Bax protein, and SNB
      motoneuron number is dissociated from target muscle size in Bax-/- animals.

PMID- 15944392
TI  - The endogenous cannabinoid anandamide and its synthetic analog R(+)
      methanandamide are intravenously self-administered by squirrel monkeys.
AB  - Anandamide, an endogenous ligand for brain cannabinoid CB(1) receptors, produces
      many behavioral effects similar to those of Delta(9)-tetrahydrocannabinol (THC),
      the main psychoactive ingredient in marijuana. Reinforcing effects of THC have
      been demonstrated in experimental animals, but there is only indirect evidence
      that endogenous cannabinoids such as anandamide participate in brain reward
      processes. We now show that anandamide serves as an effective reinforcer of drug
      taking behavior when self-administered intravenously by squirrel monkeys. We also
      show that methanandamide, a synthetic long-lasting anandamide analog, similarly
      serves as a reinforcer of drug-taking behavior. Finally, we show that the
      reinforcing effects of both anandamide and methanandamide are blocked by
      pretreatment with the cannabinoid CB(1) receptor antagonist rimonabant
      (SR141716). These findings strongly suggest that release of endogenous
      cannabinoids is involved in brain reward processes and that activation of
      cannabinoid CB(1) receptors by anandamide could be part of the signaling of
      natural rewarding events.

PMID- 15944393
TI  - Neural basis for a powerful static motion illusion.
AB  - Most people see movement in Figure 1, although the image is static. Motion is
      seen from black --> blue --> white --> yellow --> black. Many hypotheses for the
      illusory motion have been proposed, although none have been tested
      physiologically. We found that the illusion works well even if it is achromatic:
      yellow is replaced with light gray, and blue is replaced with dark gray. We show
      that the critical feature for inducing illusory motion is the luminance
      relationship of the static elements. Illusory motion is seen from black --> dark
      gray --> white --> light gray --> black. In psychophysical experiments, we found
      that all four pairs of adjacent elements when presented alone each produced
      illusory motion consistent with the original illusion, a result not expected from
      any current models. We also show that direction-selective neurons in macaque
      visual cortex gave directional responses to the same static element pairs, also
      in a direction consistent with the illusory motion. This is the first
      demonstration of directional responses by single neurons to static displays and
      supports a model in which low-level, first-order motion detectors interpret
      contrast-dependent differences in response timing as motion. We demonstrate that
      this illusion is a static version of four-stroke apparent motion.

PMID- 15944394
TI  - Stimulus history reliably shapes action potential waveforms of cortical neurons.
AB  - Action potentials have been shown to shunt synaptic charge to a degree that
      depends on their waveform. In this way, they participate in synaptic integration,
      and thus in the probability of generating succeeding action potentials, in a
      shape-dependent way. Here we test whether the different action potential
      waveforms produced during dynamical stimulation in a single cortical neuron carry
      information about the conductance stimulus history. When pyramidal neurons in rat
      visual cortex were driven by a conductance stimulus that resembles natural
      synaptic input, somatic action potential waveforms showed a large variability
      that reliably signaled the history of the input for up to 50 ms before the spike.
      The correlation between stimulus history and action potential waveforms had low
      noise, resulting in information rates that were three to four times larger than
      for the instantaneous spike rate. The reliable correlation between stimulus
      history and spike waveforms then acts as a local encoding at the single-cell
      level. It also directly affects neuronal communication as different waveforms
      influence the production of succeeding spikes via differential shunting of
      synaptic charge. Modeling was used to show that slow conductances can implement
      memory of the stimulus history in cortical neurons, encoding this information in
      the spike shape.

PMID- 15944395
TI  - Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription
      factors.
AB  - The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays
      an important role in controlling cell proliferation and differentiation.
      C/EBPalpha is a particularly potent regulator of cell-cycle exit and is induced
      in terminally differentiating adipocytes and myeloid cells, where it also
      activates differentiation-specific genes. The growth-inhibiting activity of
      C/EBPalpha suppresses tumorigenesis in myeloid cells and possibly other tissues.
      In addition, recent work has identified C/EBPalpha as a component of the p53
      regulated growth arrest response elicited by DNA damage in epidermal
      keratinocytes. Several studies have explored the mechanism by which C/EBPalpha
      blocks cell-cycle progression at the G1-S boundary, and several models have been
      proposed but no universally accepted mechanism has emerged. Controversial issues
      include whether C/EBPalpha acts through an 'off-DNA' mechanism to inhibit cyclin
      dependent kinases, and whether and how it functions with the RB-E2F system to
      repress transcription of S-phase genes. Other C/EBP-family members have also been
      implicated in positive and negative control of cell proliferation, and the
      mechanisms underlying their growth-regulatory activities are beginning to be
      elucidated.

PMID- 15944396
TI  - RhoB regulates endosome transport by promoting actin assembly on endosomal
      membranes through Dia1.
AB  - Rho GTPases are crucial regulators of the actin cytoskeleton and they play a role
      in the control of membrane trafficking. In contrast to the close family members
      RhoA and RhoC, RhoB localises to endosomes and delays epidermal growth factor
      receptor traffic. Here, we show that activated RhoB induces the peripheral
      distribution of endosomes, which align along subcortical actin stress fibres and
      are surrounded by an actin coat. The Diaphanous-related formin, Dia1, is
      recruited to endosomes by activated RhoB. Dia1 is required for the formation of
      the actin coat around endosomes downstream of RhoB, connecting membrane
      trafficking with the regulation of actin dynamics.

PMID- 15944397
TI  - PLCgamma1 is essential for early events in integrin signalling required for cell
      motility.
AB  - Cell motility is a critical event in many processes and is underlined by complex
      signalling interactions. Although many components have been implicated in
      different forms of cell migration, identification of early key mediators of these
      events has proved difficult. One potential signalling intermediate, PLCgamma1,
      has previously been implicated in growth-factor-mediated chemotaxis but its
      position and roles in more-complex motility events remain poorly understood. This
      study links PLCgamma1 to early, integrin-regulated changes leading to cell
      motility. The key role of PLCgamma1 was supported by findings that specific
      depletion of PLCgamma1 by small interfering (si)RNA, or by pharmacological
      inhibition, or the absence of this isoform in PLCgamma1(-/-) cells resulted in
      the failure to form cell protrusions and undergo cell spreading and elongation in
      response to integrin engagement. This integrin-PLCgamma1 pathway was shown to
      underlie motility processes involved in morphogenesis of endothelial cells on
      basement membranes and invasion of cancer cells into such three-dimensional
      matrices. By combining cellular and biochemical approaches, we have further
      characterized this signalling pathway. Upstream of PLCgamma1 activity, beta1
      integrin and Src kinase are demonstrated to be essential for phosphorylation of
      PLCgamma1, formation of protein complexes and accumulation of intracellular
      calcium. Cancer cell invasion and the early morphological changes associated with
      cell motility were abolished by inhibition of beta1 integrin or Src. Our findings
      establish PLCgamma1 as a key player in integrin-mediated cell motility processes
      and identify other critical components of the signalling pathway involved in
      establishing a motile phenotype. This suggests a more general role for PLCgamma1
      in cell motility, functioning as a mediator of both growth factor and integrin
      initiated signals.

PMID- 15944398
TI  - Activation of EGF receptor endocytosis and ERK1/2 signaling by BPGAP1 requires
      direct interaction with EEN/endophilin II and a functional RhoGAP domain.
AB  - Rho GTPases are important regulators for cell dynamics. They are activated by
      guanine nucleotide exchange factors and inactivated by GTPase-activating proteins
      (GAPs). We recently identified a novel RhoGAP, BPGAP1, that uses the BNIP-2 and
      Cdc42GAP homology (BCH) domain, RhoGAP domain and proline-rich region to regulate
      cell morphology and migration. To further explore its roles in intracellular
      signaling, we employed protein precipitations and matrix-assisted laser
      desorption/ionization mass-spectrometry and identified EEN/endophilin II as a
      novel partner of BPGAP1. EEN is a member of the endocytic endophilin family but
      its function in regulating endocytosis remains unclear. Pull-down and co
      immunoprecipitation studies with deletion mutants confirmed that EEN interacted
      directly with BPGAP1 via its Src homology 3 (SH3) domain binding to the proline
      rich region 182-PPPRPPLP-189 of BPGAP1, with prolines 184 and 186 being
      indispensable for this interaction. Overexpression of EEN or BPGAP1 alone induced
      EGF-stimulated receptor endocytosis and ERK1/2 phosphorylation. These processes
      were further enhanced when EEN was present together with the wildtype but not
      with the non-interactive proline mutant of BPGAP1. However, EEN lacking the SH3
      domain served as a dominant negative mutant that completely inhibited these
      effects. Furthermore, BPGAP1 with a catalytically inactive GAP domain also
      blocked the effect of EEN and/or BPGAP1 in EGF receptor endocytosis and
      concomitantly reduced their level of augmentation for ERK1/2 phosphorylation. Our
      findings reveal a concomitant activation of endocytosis and ERK signaling by
      BPGAP1 via the coupling of its proline-rich region, which targets EEN and its
      functional GAP domain. BPGAP1 could therefore provide an important link between
      cytoskeletal network, endocytic trafficking and Ras/MAPK signaling.

PMID- 15944399
TI  - Spatial re-organisation of cortical microtubules in vivo during polarisation and
      asymmetric division of Fucus zygotes.
AB  - Fucus zygotes polarise and germinate a rhizoid before their first asymmetrical
      division. The role of microtubules (MTs) in orienting the first division plane
      has been extensively studied by immunofluorescence approaches. In the present
      study, the re-organisation of MT arrays during the development of Fucus zygotes
      and embryos was followed in vivo after microinjection of fluorescent tubulin. A
      dynamic cortical MT array that shows dramatic reorganization during zygote
      polarization was detected for the first time. Randomly distributed cortical MTs
      were redistributed to the presumptive rhizoid site by the time of polarisation
      and well before rhizoid germination. The cortical MT re-organisation occurs
      independently of centrosome separation and nucleation. By the time of mitosis the
      cortical array depolymerised to cortical foci in regions from which it also
      reformed following mitosis, suggesting that it is nucleated from cortical sites.
      We confirm previous indications from immunodetection studies that centrosomal
      alignment and nuclear rotation occur via MT connexions to stabilised cortical
      sites and that definitive alignment is post-metaphasic. Finally, we show that
      cortical MTs align parallel to the growth axis during rhizoid tip growth and our
      results suggest that they may be involved in regulating rhizoid growth by shaping
      the rhizoid and containing turgor pressure.

PMID- 15944400
TI  - Urokinase-induced activation of the gp130/Tyk2/Stat3 pathway mediates a pro
      inflammatory effect in human mesangial cells via expression of the anaphylatoxin
      C5a receptor.
AB  - Glomerular mesangial cells (MCs) are central to the pathogenesis of progressive
      glomeruli-associated renal diseases. However, molecular mechanisms underlying
      changes in MC functions still remain poorly understood. Here, we show that in
      MCs, the urokinase-type plasminogen activator (uPA) induces, via its specific
      receptor (uPAR, CD87), upregulated expression of the complement anaphylatoxin C5a
      receptor (C5aR, CD88), and modulates C5a-dependent functional responses. This
      effect is mediated via the interaction of the uPA-specific receptor (uPAR, CD87)
      and gp130, a signal transducing subunit of the receptor complexes for the IL-6
      cytokine family. The Janus kinase Tyk2 and the transcription factor Stat3 serve
      as downstream components in the signaling cascade resulting in upregulation of
      C5aR expression. In vivo, expression of C5aR and uPAR was increased in the
      mesangium of wild-type mice in a lipopolysaccharide (LPS)-induced model of
      inflammation, whereas in uPAR(-/-) animals C5aR expression remained unchanged.
      This is the first demonstration in vitro and in vivo that uPA acts in MCs as a
      modulator of immune responses via control of immune-competent receptors. The data
      suggest a novel role for uPA/uPAR in glomeruli-associated renal failure via a
      signaling cross-talk between the fibrinolytic and immune systems.

PMID- 15944401
TI  - Two novel proteins recruited by synaptonemal complex protein 1 (SYCP1) are at the
      centre of meiosis.
AB  - Completion of meiosis in mammals depends on the formation of the synaptonemal
      complex, a tripartite structure that physically links homologous chromosomes
      during prophase I. Several components of the synaptonemal complex are known,
      including constituents of the cohesin core, the axial/lateral element and the
      transverse filaments. No protein has previously been identified as an exclusive
      component of the central element. Mutations in some synaptonemal-complex proteins
      results in impaired meiosis. In humans, cases of male infertility have been
      associated with failure to build the synaptonemal complex. To search for new
      components of the meiotic machinery, we have used data from microarray expression
      profiling and found two proteins localising solely to the central element of the
      mammalian synaptonemal complex. These new proteins, SYCE1 and CESC1, interact
      with the transverse filament protein SYCP1, and their localisation to the central
      element appears to depend on recruitment by SYCP1. This suggests a role for SYCE1
      and CESC1 in synaptonemal-complex assembly, and perhaps also stability and
      recombination.

PMID- 15944402
TI  - Three-dimensional polarization sensitizes hepatocytes to Fas/CD95 apoptotic
      signalling.
AB  - Maintenance of epithelial cell shape and polarity determines many vital cell
      functions, including the appropriate response to external stimuli. Murine
      hepatocytes cultured in a three-dimensional Matrigel matrix formed highly
      polarized organoids characterized by specific localization of an ERM
      (ezrin/radixin/moesin) protein, radixin, at microvillus-lined membrane domains.
      These apical domains surrounded a lumen and were bordered by tight junctions. The
      hepatocyte organoids were functional as judged by the high level of albumin
      secretion and accumulation of bilirubin. Stimulation of the Fas/CD95 death
      receptor, which is highly hepatotoxic in vivo, was a strong inducer of apoptosis
      in the polarized organoids. This was in sharp contrast to the monolayer
      hepatocyte cultures, which were protected from death by exacerbated NF-kappaB
      signalling following engagement of the death receptors. Thus, hepatocytes in
      polarized, functional organoids modulate an intracellular signal transduction
      pathway, allowing the recapitulation of their physiological response to an
      apoptotic stimulus.

PMID- 15944403
TI  - A phenylalanine-based folding determinant in intestinal sucrase-isomaltase that
      functions in the context of a quality control mechanism beyond the endoplasmic
      reticulum.
AB  - Phenotype II of congenital sucrase-isomaltase deficiency in man is characterized
      by a retention of the brush border protein sucrase-isomaltase (SI) in the ER/cis
      Golgi intermediate compartment (ERGIC) and the cis-Golgi. The transport block is
      due to the substitution of a glutamine by a proline at amino acid residue 1098
      that generates a temperature-sensitive mutant enzyme, SI(Q1098P), the transport
      of which is regulated by several cycles of anterograde and retrograde transport
      between the ER and the cis-Golgi (Propsting, M. J., Jacob, R. and Naim, H. Y.
      (2003). J. Biol. Chem. 278, 16310-16314). A quality control beyond the ER has
      been proposed that implicates a retention signal or a folding determinant
      elicited by the Q1098P mutation. We have used alanine-scanning mutagenesis to
      screen upstream and downstream regions flanking Q(1098) and identified a putative
      motif, F(1093)-x-F(1095)-x-x-x-F(1099) that is likely to be implicated in sensing
      the folding and subsequent trafficking of SI from the ER to the Golgi. The
      characteristics of this motif are three phenylalanine residues that upon
      substitution by alanine generate the temperature-sensitive SI(Q1098P) phenotype.
      This mutant protein undergoes transport arrest in the ERGIC and cis-Golgi
      compartments and acquires correct folding and functional activity at reduced
      temperatures as a consequence of cycles of anterograde and retrograde transport
      between the ER and cis-Golgi. Other amino acid residues in this motif are not
      significant in the context of phenotype II. We propose that the phenylalanine
      cluster is required for shielding a folding determinant in the extracellular
      domain of SI; substitution of a Q by a P at residue 1098 of sucrase disrupts this
      determinant and elicits retention of SI(Q1098P) in ERGIC and cis-Golgi in
      phenotype II of CSID.

PMID- 15944404
TI  - Access and utilization of HIV treatment and services among women sex workers in
      Vancouver's Downtown Eastside.
AB  - Many HIV-infected women are not realizing the benefits of highly active
      antiretroviral therapy (HAART) despite significant advancements in treatment.
      Women in Vancouver's Downtown Eastside (DTES) are highly marginalized and
      struggle with multiple morbidities, unstable housing, addiction, survival sex,
      and elevated risk of sexual and drug-related harms, including HIV infection.
      Although recent studies have identified the heightened risk of HIV infection
      among women engaged in sex work and injection drug use, the uptake of HIV care
      among this population has received little attention. The objectives of this study
      are to evaluate the needs of women engaged in survival sex work and to assess
      utilization and acceptance of HAART. During November 2003, a baseline needs
      assessment was conducted among 159 women through a low-threshold drop-in centre
      servicing street-level sex workers in Vancouver. Cross-sectional data were used
      to describe the sociodemographic characteristics, drug use patterns,
      HIV/hepatitis C virus (HCV) testing and status, and attitudes towards HAART. High
      rates of cocaine injection, heroin injection, and smokeable crack cocaine use
      reflect the vulnerable and chaotic nature of this population. Although
      preliminary findings suggest an overall high uptake of health and social
      services, there was limited attention to HIV care with only 9% of the women on
      HAART. Self-reported barriers to accessing treatment were largely attributed to
      misinformation and misconceptions about treatment. Given the acceptability of
      accessing HAART through community interventions and women specific services, this
      study highlights the potential to reach this highly marginalized group and
      provides valuable baseline information on a population that has remained largely
      outside consistent HIV care.

PMID- 15944405
TI  - PTSD and depression among displaced Chinese workers after the World Trade Center
      attack: a follow-up study.
AB  - We conducted a follow-up assessment to assess the development of Posttraumatic
      Stress Disorder (PTSD) and depression among Chinese immigrants after the World
      Trade Center attack. Sixty-five Chinese displaced workers who were originally
      interviewed in May 2002 were re-interviewed in March 2003. Whereas depression
      scores decreased over time, average PTSD scores remained unchanged. The
      trajectory of posttraumatic stress symptoms was more complex, with an increasing
      number of individuals who show no or little emotional health problems and another
      increasing group of individuals with exacerbated posttraumatic stress symptoms.
      Although the mean values of the re-experiencing and hypervigilance cluster did
      not change over time, the mean value of the avoidance/numbing cluster increased
      significantly from time 1 (M= 4.60, SD = 4.98) to time 2 (M= 6.34, SD = 4.24),
      (F1.61=5.69,P= .02). A higher proportion of subjects met diagnostic criteria of
      PTSD at time 2 (27%) than at time 1 (21%). The study highlights the importance of
      ongoing mental health surveillance of diverse cultural and linguistic groups
      after a major traumatic event.

PMID- 15944406
TI  - Chaperonin GroEL meets the substrate protein as a "load" of the rings.
AB  - Chaperonin GroEL is an essential molecular chaperone that assists protein folding
      in the cell. With the aid of cochaperonin GroES and ATP, double ring-shaped GroEL
      encapsulates non-native substrate proteins inside the cavity of the GroEL-ES
      complex. Although extensive studies have revealed the outline of GroEL mechanism
      over the past decade, central questions remain: What are the in vivo substrate
      proteins? How does GroEL encapsulate the substrates inside the cavity in spite of
      an apparent entropic difficulty? Is the folding inside the GroEL-ES cavity the
      same as bulk spontaneous folding? In this review I summarize the recent progress
      on in vivo and in vitro aspects of GroEL. In particular, emerging evidence shows
      that the substrate protein itself influences the chaperonin GroEL structure and
      reaction cycle. Finally I propose the mechanistic similarity between GroEL and
      kinesin, a molecular motor that moves along a microtubule in an ATP-dependent
      manner.

PMID- 15944407
TI  - Roles of molecular chaperones in endoplasmic reticulum (ER) quality control and
      ER-associated degradation (ERAD).
AB  - Secreted proteins are synthesized at the endoplasmic reticulum (ER), and a
      quality control mechanism in the ER is essential to maintain secretory pathway
      homeostasis. Newly synthesized soluble and integral membrane secreted proteins
      fold into their native conformations with the aid of ER molecular chaperones
      before they are transported to post-ER compartments. However, terminally mis
      folded proteins may be retained in the ER and degraded by a process called ER
      associated degradation (ERAD). Recent studies using yeast have shown that
      molecular chaperones both in the ER and in the cytosol play key roles during the
      ERAD of mis-folded proteins. One important role for chaperones during ERAD is to
      prevent substrate protein aggregation. Substrate selection is another important
      role for molecular chaperones during ERAD.

PMID- 15944408
TI  - Roles of C-terminal processing, and involvement in transacylation reaction of
      human group IVC phospholipase A2 (cPLA2gamma).
AB  - The phospholipase A2s (PLA2s) are a diverse group of enzymes that hydrolyze the
      sn-2 fatty acid from phospholipids and play a role in a wide range of
      physiological functions. A 61-kDa calcium-independent PLA2, termed cPLA2gamma,
      was identified as an ortholog of cPLA2alpha with approximately 30% overall
      sequence identity. cPLA2gamma contains a potential prenylation motif at its C
      terminus, and is known to have PLA2 and lysophospholipase activities, but its
      physiological roles have not been clarified. In the present study, we expressed
      various forms of recombinant cPLA2gamma, including non-prenylated and non-cleaved
      forms, in order to investigate the effects of C-terminal processing. We examined
      the expression of the wild type and non-prenylated (SCLA) forms of cPLA2gamma,
      and found that the SCLA form was expressed normally and retained almost full
      activity. Expression of the prenylated and non-cleaved form of cPLA2gamma using
      yeast mutants lacking prenyl protein proteases AFC1 (a-factor-converting enzyme)
      and RCE1 (Ras-converting enzyme) revealed decreased expression in the mutant
      strain compared to that in the wild type yeast, suggesting that complete C
      terminal processing is important for the functional expression of cPLA2gamma. In
      addition, cPLA2gamma was found to have coenzyme A (CoA)-independent
      transacylation and lysophospholipid (LPL) dismutase (LPLase/transacylase)
      activities, suggesting that it may be involved in fatty acid remodeling of
      phospholipids and the clearance of toxic lysophospholipids in cells.

PMID- 15944409
TI  - Stabilization due to dimer formation of phosphoribosyl anthranilate isomerase
      from Thermus thermophilus HB8: X-ray Analysis and DSC experiments.
AB  - The crystal structure of phosphoribosyl anthranilate isomerase (PRAI) from
      Thermus thermophilus HB8 (TtPRAI) was solved at 2.0 A resolution. The overall
      structure of TtPRAI with a dimeric structure was quite similar to that of PRAI
      from Thermotoga maritima (TmPRAI). In order to elucidate the stabilization
      mechanism of TtPRAI, its physicochemical properties were examined using DSC, CD,
      and analytical centrifugation at various pHs in relation to the association
      dissociation of the subunits. Based on the experimental results for TtPRAI and
      the structural information on TtPRAI and TmPRAI, we found that: (i) the
      denaturation of TtPRAI at acidic pH is correlated with the dissociation of its
      dimeric form; (ii) the hydrophobic interaction of TtPRAI in the monomer structure
      is slightly greater than that of TmPRAI, but dimer interface of the TmPRAI is
      remarkably greater; (iii) the contributions of hydrogen bonds and ion bonds to
      the stability are similar to each other; and (iv) destabilization due to the
      presence of cavities in TtPRAI is greater than that of TmPRAI in both the monomer
      and dimer structures.

PMID- 15944410
TI  - Thrombomodulin enhances the invasive activity of mouse mammary tumor cells.
AB  - Thrombomodulin (TM) is a thrombin receptor on the surface of endothelial cells
      that converts thrombin from a procoagulant to an anticoagulant. Thrombin promotes
      invasion by various tumor cells, and positive or negative correlations are found
      between the expression of TM and tumorigenesis in some patients. In this study,
      we used an invasion assay to investigate the effect of TM on the invasive
      activity of a mouse mammary tumor cell line, MMT cells, and the effects of TM
      were compared with those of thrombin as a positive control. In the presence of 1%
      fetal calf serum (FCS), TM significantly stimulated MMT cell invasion in a dose
      dependent manner, resulting in an approximately 3-fold increase at 1-10 pg/ml
      over the untreated control. Thrombin also caused a similar degree of stimulation
      at 50 ng/ml. Since thrombin activity was detected in the components of the assay
      system, an invasion assay was also performed in a thrombin-activity-depleted
      assay system constructed to eliminate the effect of thrombin activity; TM (10
      pg/ml) plus thrombin (1 pg/ml) stimulated invasion by approximately 3.5-fold in
      this assay system. Hirudin, a specific thrombin inhibitor, inhibited stimulation
      by TM as well as by thrombin in both the presence and absence of 1% FCS.
      Investigations of the effects of TM on proliferation, adhesion and chemotaxis to
      clarify the mechanism of stimulation by TM revealed that TM does not affect
      proliferation or adhesion in the presence of 1% FCS, but stimulates chemotaxis by
      approximately 2.3-fold. Similar results were obtained in experiments using
      thrombin. TM (10 pg/ml) plus thrombin (1 pg/ml), on the other hand, stimulated
      chemotaxis by approximately 2.3-fold in the thrombin-activity-depleted assay
      system. Binding studies using [125I]-thrombin revealed that the cells have
      specific saturable binding sites for thrombin. These results show that TM
      stimulates the invasive activity of MMT cells, probably by acting as a cofactor
      for the thrombin-stimulated invasion of the cells via its receptor and lowering
      the effective concentration of thrombin. The findings also indicate that the
      stimulation of invasive activity in the presence of 1% FCS and in the thrombin
      activity-depleted assay system may mainly be mediated by the stimulation of
      chemotaxis.

PMID- 15944411
TI  - Structural basis for thermostability of endo-1,5-alpha-L-arabinanase from
      Bacillus thermodenitrificans TS-3.
AB  - The crystal structure of a thermostable endo-1,5-alpha-L-arabinanase, ABN-TS,
      from Bacillus thermodenitrificans TS-3 was determined at 1.9 A to an R-factor of
      18.3% and an R-free-factor of 22.5%. The enzyme molecule has a five-bladed beta
      propeller fold. The substrate-binding cleft formed across one face of the
      propeller is open on both sides to allow random binding of several sugar units in
      the polymeric substrate arabinan. The beta-propeller fold is stabilized through a
      ring closure. ABN-TS exhibits a new closure-mode involving residues in the N
      terminal region: Phe7 to Gly21 exhibit hydrogen bonds and hydrophobic
      interactions with the first and last blades, and Phe4 links the second and third
      blades through a hydrogen bond and an aromatic stacking interaction,
      respectively. The role of the N-terminal region in the thermostability was
      confirmed with a mutant lacking 16 amino acid residues from the N-terminus of ABN
      TS.

PMID- 15944412
TI  - Isolation of a Drosophila gene coding for a protein containing a novel
      phosphatidylserine-binding motif.
AB  - To elucidate the molecular basis of the binding of proteins to the membrane
      phospholipid phosphatidylserine (PS), we characterized PS-binding peptides
      isolated from a phage display library. Amino acid sequences deduced from the
      nucleotide sequences of over 60 phage clones isolated revealed that there was no
      common primary structure among these peptides, but all peptides were rich in
      basic amino acid residues. In particular, 15 clones encoded peptides that
      contained contiguous arginine residues. Characterization of two such peptides in
      more detail showed that they bound to PS, and to a much lower extent to other
      phospholipids, including phosphatidylinositol, phosphatidylethanolamine, and
      phosphatidylcholine. Unlike other Ca2+-dependent PS-binding proteins, these
      peptides did not require Ca2+ for binding to PS, and the addition of Ca2+ did not
      alter the phospholipid specificity. Substitution of one of the two RR sequences
      in one peptide by alanine had no effect, but that of both sequences completely
      abolished the activity. Furthermore, we identified a Drosophila gene coding for a
      presumed nuclear protein that shares an amino acid sequence, including a RR
      residue, with one of the two PS-binding peptides. This protein bound to PS partly
      depending on the presence of the RR residue. These results allowed us to conclude
      that an amino acid sequence including contiguous arginine residues is a novel
      motif that defines Ca2+-independent PS-binding activity.

PMID- 15944413
TI  - Expression and characterization of a baseplate protein for bacteriophage Mu,
      gp44.
AB  - The gene product of gene 44 of Mu phage (gp44) is an essential protein for
      baseplate assembly and has been designated as gpP, a traditional genetic
      assignment. The function of gp44 during the assembly or infection process is not
      known. In the present study, we purified the recombinant gp44 and characterized
      it by analytical ultracentrifugation and differential scanning microcalorimetry.
      The results indicate that gp44 forms a trimer comprising a complex consisting of
      the 42 kDa and 40 kDa subunits that had been cleaved in the C-terminal region.
      Thermodynamic analysis also suggested that the C-terminal region forms a flexible
      domain.

PMID- 15944414
TI  - CD36 is not involved in scavenger receptor-mediated endocytic uptake of
      glycolaldehyde- and methylglyoxal-modified proteins by liver endothelial cells.
AB  - Circulating proteins modified by advanced glycation end-products (AGE) are mainly
      taken up by liver endothelial cells (LECs) via scavenger receptor-mediated
      endocytosis. Endocytic uptake of chemically modified proteins by macrophages and
      macrophage-derived cells is mediated by class A scavenger receptor (SR-A) and
      CD36. In a previous study using SR-A knockout mice, we demonstrated that SR-A is
      not involved in endocytic uptake of AGE proteins by LECs [Matsumoto et al. (2000)
      Biochem. J. 352, 233-240]. The present study was conducted to determine the
      contribution of CD36 to this process. Glycolaldehyde-modified BSA (GA-BSA) and
      methylglyoxal-modified BSA (MG-BSA) were used as AGE proteins. 125I-GA-BSA and
      125I-MG-BSA underwent endocytic degradation by these cells at 37 degrees C, and
      this process was inhibited by several ligands for the scavenger receptors.
      However, this endocytic uptake of 125I-GA-BSA by LECs was not inhibited by a
      neutralizing anti-CD36 antibody. Similarly, hepatic uptake of (111)In-GA-BSA
      after its intravenous injection was not significantly attenuated by co
      administration of the anti-CD36 antibody. These results clarify that CD36 does
      not play a significant role in elimination of GA-BSA and MG-BSA from the
      circulation, suggesting that the receptor involved in endocytic uptake of
      circulating AGE proteins by LEC is not SR-A or CD36.

PMID- 15944415
TI  - A novel protein specifically interacting with Homer2 regulates ubiquitin
      proteasome systems.
AB  - Homer family proteins are encoded by three genes, homer1, 2 and 3. Most of these
      proteins are expressed constitutively in nervous systems and accumulated in
      postsynaptic regions. However, the functional significance of these proteins,
      especially the significance of the distinction among the proteins encoded by
      homer1, 2 and 3, is still obscure. In the present study, we isolated a cDNA clone
      encoding a novel protein by two-hybrid system screening using the C-terminal half
      of Homer2b as the bait. This protein, termed 2B28, has 297 amino acid residues
      and contains three major domains: a UBA domain, a coiled-coil region, and a UBX
      domain. When expressed in HEK293T cells, 2B28 showed colocalization with
      uniquitin and enhanced the expression levels of IkappaB or Homer1a proteins,
      which are known to be degraded by proteasomes, indicating that 2B28 is involved
      in ubiquitin-proteasome functions. 2B28 specifically interacted and colocalized
      with Homer2 proteins, but not with Homer1 proteins. So far, we have identified no
      counterpart of 2B28 for Homer1 experimentally or in the protein databases. These
      results suggest that the specific interaction of 2B28 with Homer2 may play a role
      in regulation of protein degradation by ubiquitin-proteasome systems and that
      this function may be specific to Homer2 proteins among Homer family proteins.

PMID- 15944416
TI  - Effects of Y132H and F145L substitutions on the activity, azole resistance and
      spectral properties of Candida albicans sterol 14-demethylase P450 (CYP51): a
      live example showing the selection of altered P450 through interaction with
      environmental compounds.
AB  - Three variants of Candida albicans CYP51 (sterol 14-demethylase P450) having
      Y132H and/or F145L substitutions were purified and characterized to reveal the
      effects of these amino acid substitutions on the enzymatic properties and azole
      resistance of the enzyme. Y132H and F145L substitutions modified the spectral
      properties of the enzyme, suggesting that they caused some structural change
      modifying the heme environments of CYP51. Y132H and F145L substitutions increased
      the resistance of the enzyme to azole compounds but considerably decreased the
      catalytic activity. This fact represents a trade-off between acquisition of azole
      resistance and maintenance of high activity in the CYP51 having Y132H and F145L
      substitutions. A fluconazole-resistant C. albicans strain DUMC136 isolated from
      patients receiving long-term azole treatment was a homozygote of the altered
      CYP51 having Y132H and F145L substitutions. However, neither of these
      substitutions was found in CYP51 of wild-type C. albicans so far studied. These
      facts suggest that the azole-resistant variant having Y132H and/or F145L
      substitutions might be selected only under azole-rich environments because of its
      azole resistance and impaired catalytic activity. This may be a live example
      showing one of the important processes of P450 diversification, the selection of
      altered P450 through the interaction with environmental compounds.

PMID- 15944417
TI  - Phospho-pivot modeling predicts specific interactions of protein phosphatase-1
      with a phospho-inhibitor protein CPI-17.
AB  - Phospho-amino acids in proteins are directly associated with phospho-receptor
      proteins, including protein phosphatases. Here we produced and tested a scheme
      for docking together interacting phospho-proteins whose monomeric 3D structures
      were known. The phosphate of calyculin A, an inhibitor for protein phosphatase-1
      and 2A (PP1 and PP2A), or phospho-CPI-17, a PP1-specific inhibitor protein, was
      docked at the active site of PP1. First, a library of 186,624 virtual complexes
      was generated in silico, by pivoting the phospho-ligand at the phosphorus atom by
      step every 5 degrees on three rotational axes. These models were then graded for
      probability according to atomic proximity between two molecules. The predicted
      structure of PP1 x calyculin A complex fitted to the crystal structure with
      r.m.s.d. of 0.23 A, providing a validate test of the modeling method. Modeling of
      PP1 x phospho-CPI-17 complex yielded one converged structure. The segment of CPI
      17 around phospho-Thr38 is predicted to fit in the active site of PP1. Positive
      charges at Arg33/36 of CPI-17 are in close proximity to Glu274 of PP1, where the
      sequence is unique among Ser/Thr phosphatases. Single mutations of these residues
      in PP1 reduced the affinity against phospho-CPI-17. Thus, the interface of the
      PP1 x CPI-17 complex predicted by the phospho-pivot modeling accounts for the
      specificity of CPI-17 against PP1.

PMID- 15944418
TI  - Effects of mutation at methionine-42 of Escherichia coli dihydrofolate reductase
      on stability and function: implication of hydrophobic interactions.
AB  - Methionine-42, distal to the active site of Escherichia coli dihydrofolate
      reductase, was substituted by site-directed mutagenesis with 14 amino acids (Ala,
      Cys, Glu, Gln, Gly, His, Ile, Leu, Pro, Ser, Thr, Trp, Tyr, and Val) to elucidate
      its role in the stability and function of this enzyme. Far-ultraviolet circular
      dichroism spectra of these mutants showed a distinctive negative peak at around
      230 nm beside 220 nm, depending on the hydrophobicity of the amino acids
      introduced. The fluorescence intensity also increased in an order similar to that
      of the amino acids. These spectroscopic data suggest that the mutations do not
      affect the secondary structure, but strongly perturb the exciton coupling between
      Trp47 and Trp74. The free energy of urea unfolding, deltaG(o)u, increased with
      increases in the side-chain hydrophobicity in the range 2.96-6.40 kcal x mol(-1),
      which includes the value for the wild-type enzyme (6.08 kcal x mol(-1)). The
      steady-state kinetic parameters, Km and kcat, also increased with increases in
      the side-chain hydrophobicity, with the M42W mutant showing the largest increases
      in Km (35-fold) and kcat (4.3-fold) compared with the wild-type enzyme. These
      results demonstrate that site 42 distal to the active site plays an important
      role in the stability and function of this enzyme, and that the main effect of
      the mutations is to modify of hydrophobic interactions with the residues
      surrounding this position.

PMID- 15944419
TI  - Images in clinical medicine. Myiasis due to Dermatobia hominis (Human Botfly).

PMID- 15944420
TI  - Managing conflict at the end of life.

PMID- 15944421
TI  - Patients in a persistent vegetative state--a Dutch perspective.

PMID- 15944422
TI  - The multiplicity of thyroid nodules and carcinomas.

PMID- 15944423
TI  - A randomized trial of intensive lipid-lowering therapy in calcific aortic
      stenosis.
AB  - BACKGROUND: Calcific aortic stenosis has many characteristics in common with
      atherosclerosis, including hypercholesterolemia. We hypothesized that intensive
      lipid-lowering therapy would halt the progression of calcific aortic stenosis or
      induce its regression. METHODS: In this double-blind, placebo-controlled trial,
      patients with calcific aortic stenosis were randomly assigned to receive either
      80 mg of atorvastatin daily or a matched placebo. Aortic-valve stenosis and
      calcification were assessed with the use of Doppler echocardiography and helical
      computed tomography, respectively. The primary end points were change in aortic
      jet velocity and aortic-valve calcium score. RESULTS: Seventy-seven patients were
      assigned to atorvastatin and 78 to placebo, with a median follow-up of 25 months
      (range, 7 to 36). Serum low-density lipoprotein cholesterol concentrations
      remained at 130+/-30 mg per deciliter in the placebo group and fell to 63+/-23 mg
      per deciliter in the atorvastatin group (P<0.001). Increases in aortic-jet
      velocity were 0.199+/-0.210 m per second per year in the atorvastatin group and
      0.203+/-0.208 m per second per year in the placebo group (P=0.95; adjusted mean
      difference, 0.002; 95 percent confidence interval, -0.066 to 0.070 m per second
      per year). Progression in valvular calcification was 22.3+/-21.0 percent per year
      in the atorvastatin group, and 21.7+/-19.8 percent per year in the placebo group
      (P=0.93; ratio of post-treatment aortic-valve calcium score, 0.998; 95 percent
      confidence interval, 0.947 to 1.050). CONCLUSIONS: Intensive lipid-lowering
      therapy does not halt the progression of calcific aortic stenosis or induce its
      regression. This study cannot exclude a small reduction in the rate of disease
      progression or a significant reduction in major clinical end points. Long-term,
      large-scale, randomized, controlled trials are needed to establish the role of
      statin therapy in patients with calcific aortic stenosis.

PMID- 15944424
TI  - Two-year outcomes after conventional or endovascular repair of abdominal aortic
      aneurysms.
AB  - BACKGROUND: Two randomized trials have shown better outcomes with elective
      endovascular repair of abdominal aortic aneurysms than with conventional open
      repair in the first month after the procedure. We investigated whether this
      advantage is sustained beyond the perioperative period. METHODS: We conducted a
      multicenter, randomized trial comparing open repair with endovascular repair in
      351 patients who had received a diagnosis of abdominal aortic aneurysm of at
      least 5 cm in diameter and who were considered suitable candidates for both
      techniques. Survival after randomization was calculated with the use of Kaplan
      Meier analysis and compared with the use of the log-rank test on an intention-to
      treat-basis. RESULTS: Two years after randomization, the cumulative survival
      rates were 89.6 percent for open repair and 89.7 percent for endovascular repair
      (difference, -0.1 percentage point; 95 percent confidence interval, -6.8 to 6.7
      percentage points). The cumulative rates of aneurysm-related death were 5.7
      percent for open repair and 2.1 percent for endovascular repair (difference, 3.7
      percentage points; 95 percent confidence interval, -0.5 to 7.9 percentage
      points). This advantage of endovascular repair over open repair was entirely
      accounted for by events occurring in the perioperative period, with no
      significant difference in subsequent aneurysm-related mortality. The rate of
      survival free of moderate or severe complications was also similar in the two
      groups at two years (at 65.9 percent for open repair and 65.6 percent for
      endovascular repair; difference, 0.3 percentage point; 95 percent confidence
      interval, -10.0 to 10.6 percentage points). CONCLUSIONS: The perioperative
      survival advantage with endovascular repair as compared with open repair is not
      sustained after the first postoperative year.

PMID- 15944425
TI  - Independent clonal origins of distinct tumor foci in multifocal papillary thyroid
      carcinoma.
AB  - BACKGROUND: Papillary thyroid carcinoma is frequently multifocal. We investigated
      whether noncontiguous tumor foci arise from intraglandular metastases from a
      single primary tumor or originate as unrelated clones derived from independent
      precursors. METHODS: Using a polymerase-chain-reaction assay involving the human
      androgen receptor gene (HUMARA), we analyzed the patterns of X-chromosome
      inactivation of multiple distinct foci of well-differentiated multifocal
      papillary thyroid cancer from 17 women. RESULTS: Multiple thyroid tumor foci from
      10 of 17 patients yielded DNA of adequate quality and were heterozygous for the
      HUMARA polymorphism and hence suitable for analysis. A single X chromosome was
      inactivated in each focus, consistent with its monoclonality. When the specific
      monoclonal configurations of each patient's discrete tumor foci were compared,
      discordant patterns indicative of independent origins were observed among the
      tumors from five patients; results in the remaining five were consistent with
      either a shared or independent clonal origin. CONCLUSIONS: Individual tumor foci
      in patients with multifocal papillary thyroid cancer often arise as independent
      tumors.

PMID- 15944426
TI  - Calpains and disease.

PMID- 15944427
TI  - Images in clinical medicine. Xanthomatous pseudospectacles in familial
      hypercholesterolemia.

PMID- 15944428
TI  - Case records of the Massachusetts General Hospital. Case 17-2005. A 22-year-old
      woman with back and leg pain and respiratory failure.

PMID- 15944429
TI  - Statins for aortic stenosis.

PMID- 15944430
TI  - Endovascular repair of abdominal aortic aneurysm--round two.

PMID- 15944431
TI  - MicroRNA and lung cancer.

PMID- 15944432
TI  - Treatment of localized lymphoma.

PMID- 15944433
TI  - Phase 1 clinical trials in oncology.

PMID- 15944434
TI  - The serotonin syndrome.

PMID- 15944435
TI  - Acute doxorubicin cardiotoxicity.

PMID- 15944436
TI  - Cabergoline plus lanreotide for ectopic Cushing's syndrome.

PMID- 15944437
TI  - Evolutionary diversity and potential recombinogenic role of integration targets
      of Non-LTR retrotransposons.
AB  - Short interspersed elements (SINEs) make up a significant fraction of total DNA
      in mammalian genomes, providing a rich substrate for chromosomal rearrangements
      by SINE-SINE recombinations. Proliferation of mammalian SINEs is mediated
      primarily by long interspersed element 1 (L1) non-long terminal repeat
      retrotransposons that preferentially integrate at DNA sequence targets with an
      average length of approximately 15 bp and containing conserved endonucleolytic
      nicking signals at both ends. We report that sequence variations in the first of
      the two nicking signals, represented by a 5'-TT-AAAA consensus sequence, affect
      the position of the second signal thus leading to target site duplications (TSDs)
      of different lengths. The length distribution of TSDs appears to be affected also
      by L1-encoded enzyme variants because targets with the same 5' nicking site can
      be of different average lengths in different mammalian species. Taking this into
      account, we reanalyzed the second nicking site and found that it is larger and
      includes more conserved sites than previously appreciated, with a consensus of 5'
      ANTNTN-AA. We also studied potential involvement of the nicking sites in
      stimulating recombinations between SINEs. We determined that SINEs retaining TSDs
      with perfect 5'-TT-AAAA nicking sites appear to be lost relatively rapidly from
      the human and rat genomes and less rapidly from dog. We speculate that the
      introduction of DNA breaks induced by recurring endonucleolytic attacks at these
      sites, combined with the ubiquitousness of SINEs, may significantly promote
      recombination between repetitive elements, leading to the observed losses. At the
      same time, new L1 subfamilies may be selected for "incompatibility" with
      preexisting targets. This provides a possible driving force for the continual
      emergence of new L1 subfamilies which, in turn, may affect selection of L1
      dependent SINE subfamilies.

PMID- 15944438
TI  - Identifying the basal angiosperm node in chloroplast genome phylogenies: sampling
      one's way out of the Felsenstein zone.
AB  - While there has been strong support for Amborella and Nymphaeales (water lilies)
      as branching from basal-most nodes in the angiosperm phylogeny, this hypothesis
      has recently been challenged by phylogenetic analyses of 61 protein-coding genes
      extracted from the chloroplast genome sequences of Amborella, Nymphaea, and 12
      other available land plant chloroplast genomes. These character-rich analyses
      placed the monocots, represented by three grasses (Poaceae), as sister to all
      other extant angiosperm lineages. We have extracted protein-coding regions from
      draft sequences for six additional chloroplast genomes to test whether this
      surprising result could be an artifact of long-branch attraction due to limited
      taxon sampling. The added taxa include three monocots (Acorus, Yucca, and Typha),
      a water lily (Nuphar), a ranunculid (Ranunculus), and a gymnosperm (Ginkgo).
      Phylogenetic analyses of the expanded DNA and protein data sets together with
      microstructural characters (indels) provided unambiguous support for Amborella
      and the Nymphaeales as branching from the basal-most nodes in the angiosperm
      phylogeny. However, their relative positions proved to be dependent on the method
      of analysis, with parsimony favoring Amborella as sister to all other angiosperms
      and maximum likelihood (ML) and neighbor-joining methods favoring an Amborella +
      Nymphaeales clade as sister. The ML phylogeny supported the later hypothesis, but
      the likelihood for the former hypothesis was not significantly different.
      Parametric bootstrap analysis, single-gene phylogenies, estimated divergence
      dates, and conflicting indel characters all help to illuminate the nature of the
      conflict in resolution of the most basal nodes in the angiosperm phylogeny.
      Molecular dating analyses provided median age estimates of 161 MYA for the most
      recent common ancestor (MRCA) of all extant angiosperms and 145 MYA for the MRCA
      of monocots, magnoliids, and eudicots. Whereas long sequences reduce variance in
      branch lengths and molecular dating estimates, the impact of improved taxon
      sampling on the rooting of the angiosperm phylogeny together with the results of
      parametric bootstrap analyses demonstrate how long-branch attraction might
      mislead genome-scale phylogenetic analyses.

PMID- 15944439
TI  - Structural and functional implications of an unusual foraminiferal beta-tubulin.
AB  - We have obtained sequence data for beta-tubulin genes from eight species of
      Foraminifera (forams) and alpha-tubulin sequences from four species, sampling
      major taxonomic groups from a wide range of environments. Analysis of the beta
      tubulin sequences demonstrates that foram beta-tubulins possess the highest
      degree of divergence of any tubulin gene sequenced to date and represent a novel
      form of the protein. In contrast, foram alpha-tubulin genes resemble the
      conventional alpha-tubulins seen in other organisms. Partition homogeneity
      analysis shows that the foraminiferal beta-tubulin gene has followed an
      evolutionary path that is distinct from that of all other organisms. Our findings
      indicate that positive selective pressure occurred on the beta-tubulin subunit in
      ancestral forams prior to their diversification. The specific substitutions
      observed have implications for microtubule (MT) assembly dynamics. The regions
      most strongly affected are implicated in lateral contacts between protofilaments
      and in taxol binding. We predict that these changes strengthen lateral contacts
      between adjacent dimers in a manner similar to that induced by taxol binding,
      thus allowing the formation of the tubulin "helical filaments" observed in forams
      by electron microscopy. Our results also indicate that substantial changes to
      these portions of the beta-tubulin molecule can be made without sacrificing
      essential MT functions.

PMID- 15944440
TI  - Positive correlation between evolutionary rate and recombination rate in
      Drosophila genes with male-biased expression.
AB  - Previous studies have shown that genes that are expressed predominantly or
      exclusively in males tend to evolve rapidly in comparison to other genes. In most
      cases, however, it is unknown whether this rapid evolution is the result of
      increased positive (or sexual) selection on male-expressed traits or if it is due
      to a relaxation of selective constraints. To distinguish between these two
      possibilities, we analyzed the relationship between the nonsynonymous
      substitution rate (dN) and local recombination rate for 343 Drosophila genes that
      were classified as male, female, or nonsex biased in their expression. For the
      male-biased genes, a positive correlation between dN and recombination rate was
      observed. This can be explained by an increased rate of adaptive evolution in
      regions of higher recombination due to a reduction of Hill-Robertson
      interference. In contrast, the correlation between dN and recombination rate was
      negative for both female- and nonsex-biased genes, suggesting that these genes
      are primarily subject to purifying selection, which is expected to be less
      effective in regions of reduced recombination.

PMID- 15944441
TI  - Substitution rate and structural divergence of 5'UTR evolution: comparative
      analysis between human and cynomolgus monkey cDNAs.
AB  - The substitution rate and structural divergence in the 5'-untranslated region
      (UTR) were investigated by using human and cynomolgus monkey cDNA sequences. Due
      to the weaker functional constraint in the UTR than in the coding sequence, the
      divergence between humans and macaques would provide a good estimate of the
      nucleotide substitution rate and structural divergence in the 5'UTR. We found
      that the substitution rate in the 5'UTR (K5UTR) averaged approximately 10%-20%
      lower than the synonymous substitution rate (Ks). However, both the K5UTR and
      nonsynonymous substitution rate (Ka) were significantly higher in the testicular
      cDNAs than in the brain cDNAs, whereas the Ks did not differ. Further, an in
      silico analysis revealed that 27% (169/622) of macaque testicular cDNAs had an
      altered exon-intron structure in the 5'UTR compared with the human cDNAs. The
      fraction of cDNAs with an exon alteration was significantly higher in the
      testicular cDNAs than in the brain cDNAs. We confirmed by using reverse
      transcriptase-polymerase chain reaction that about one-third (6/16) of in silico
      "macaque-specific" exons in the 5'UTR were actually macaque specific in the
      testis. The results imply that positive selection increased K5UTR and structural
      alteration rate of a certain fraction of genes as well as Ka. We found that both
      positive and negative selection can act on the 5'UTR sequences.

PMID- 15944442
TI  - The evolution of reproductive systems and sex-determining mechanisms within rumex
      (polygonaceae) inferred from nuclear and chloroplastidial sequence data.
AB  - The genus Rumex includes hermaphroditic, polygamous, gynodioecious, monoecious,
      and dioecious species, with the dioecious species being represented by different
      sex-determining mechanisms and sex-chromosome systems. Therefore, this genus
      represents an exceptional case study to test several hypotheses concerning the
      evolution of both mating systems and the genetic control of sex determination in
      plants. Here, we compare nuclear intergenic transcribed spacers and chloroplast
      intergenic sequences of 31 species of Rumex. Our phylogenetic analysis supports a
      systematic classification of the genus, which differs from that currently
      accepted. In contrast to the current view, this new phylogeny suggests a common
      origin for all Eurasian and American dioecious species of Rumex, with gynodioecy
      as an intermediate state on the way to dioecy. Our results support the contention
      that sex determination based on the balance between the number of X chromosomes
      and the number of autosomes (X/A balance) has evolved secondarily from male
      determining Y mechanisms and that multiple sex-chromosome systems, XX/XY1Y2, were
      derived twice from an XX/XY system. The resulting phylogeny is consistent with a
      classification of Rumex species according to their basic chromosome number,
      implying that the evolution of Rumex species might have followed a process of
      chromosomal reduction from x = 10 toward x = 7 through intermediate stages (x = 9
      and x = 8).

PMID- 15944443
TI  - High-resolution phylogenetic analysis of southeastern Europe traces major
      episodes of paternal gene flow among Slavic populations.
AB  - The extent and nature of southeastern Europe (SEE) paternal genetic contribution
      to the European genetic landscape were explored based on a high-resolution Y
      chromosome analysis involving 681 males from seven populations in the region.
      Paternal lineages present in SEE were compared with previously published data
      from 81 western Eurasian populations and 5,017 Y chromosome samples. The finding
      that five major haplogroups (E3b1, I1b* (xM26), J2, R1a, and R1b) comprise more
      than 70% of SEE total genetic variation is consistent with the typical European Y
      chromosome gene pool. However, distribution of major Y chromosomal lineages and
      estimated expansion signals clarify the specific role of this region in
      structuring of European, and particularly Slavic, paternal genetic heritage.
      Contemporary Slavic paternal gene pool, mostly characterized by the predominance
      of R1a and I1b* (xM26) and scarcity of E3b1 lineages, is a result of two major
      prehistoric gene flows with opposite directions: the post-Last Glacial Maximum
      R1a expansion from east to west, the Younger Dryas-Holocene I1b* (xM26) diffusion
      out of SEE in addition to subsequent R1a and I1b* (xM26) putative gene flows
      between eastern Europe and SEE, and a rather weak extent of E3b1 diffusion toward
      regions nowadays occupied by Slavic-speaking populations.

PMID- 15944444
TI  - Population genetics of Neisseria gonorrhoeae in a high-prevalence community using
      a hypervariable outer membrane porB and 13 slowly evolving housekeeping genes.
AB  - Baltimore, Md., is an urban community with a high prevalence of Neisseria
      gonorrhoeae. Due to partially protective immune responses, introduction of new
      strains from other host populations, and exposure of N. gonorrhoeae to
      antibiotics, the phenotypic and genotypic characteristics of the circulating
      strains can fluctuate over time. Understanding the overall genetic diversity and
      population structure of N. gonorrhoeae is essential for informing public health
      interventions to eliminate this pathogen. We studied gonococci population
      genetics in Baltimore by analyzing a hypervariable and strongly selected outer
      membrane porB gene and 13 slowly evolving and presumably neutral housekeeping
      genes (abcZ, adk, aroE, fumC, gdh, glnA, gnd, pdhC, pgm, pilA, ppk, pyrD, and
      serC) in 204 isolates collected in 1991, 1996, and 2001 from male and female
      patients of two public sexually transmitted diseases clinics. Genetic diversity
      (), recombination (C), growth (g), population structure, and adaptive selection
      under codon-substitution and amino acid property models were estimated and
      compared between these two gene classes. Estimates of the F(ST) fixation index
      and the chi(2) test of sequence absolute frequencies revealed significant
      temporal substructuring for both gene types. Baltimore's N. gonorrhoeae
      populations have increased since 1991 as indicated by consistent positive values
      of g. Female patients showed similar or lower levels of and C than male patients.
      Within the MLST housekeeping genes, levels of and C ranged from 0.001-0.013 and
      0.000-0.018, respectively. Overall recombination seems to be the dominant force
      driving evolution in these populations. All loci showed amino acid sites and
      physicochemical properties under adaptive (or positive-destabilizing) selection,
      rejecting the generally assumed hypothesis of stabilizing selection for these
      MLST genes. Within the porB gene, protein I B showed higher and C values than
      protein I A. Directional positive selection possibly mediated by the immune
      system operates to a significant extent in the protein I sequences, as indicated
      by the distribution of the positively selected sites in the surface-exposed
      loops. Thirteen amino acid physicochemical properties seem to drive protein
      evolution of the PI porins in N. gonorrhoeae.

PMID- 15944445
TI  - A model-based approach for detecting coevolving positions in a molecule.
AB  - We present a new method for detecting coevolving sites in molecules. The method
      relies on a set of aligned sequences (nucleic acid or protein) and uses Markov
      models of evolution to map the substitutions that occurred at each site onto the
      branches of the underlying phylogenetic tree. This mapping takes into account the
      uncertainty over ancestral states and among-site rate variation. We then build,
      for each site, a "substitution vector" containing the posterior estimates of the
      number of substitutions in each branch. The amount of coevolution for a pair of
      sites is then measured as the Pearson correlation coefficient between the two
      corresponding substitution vectors and compared to the expectation under the null
      hypothesis of independence. We applied the method to a 79-species bacterial
      ribosomal RNA data set, for which extensive structural characterization has been
      done over the last 30 years. More than 95% of the intramolecular predicted pairs
      of sites correspond to known interacting site pairs.

PMID- 15944446
TI  - Epidemiology of first-episode psychosis: illustrating the challenges across
      diagnostic boundaries through the Cavan-Monaghan study at 8 years.
AB  - The epidemiology of first-episode psychosis is poorly understood because of the
      paucity of systematic studies, yet it constitutes the fundamental basis for
      understanding the disorder and the foundations on which clinical, biological,
      therapeutic, and long-term outcome studies are built. A particular need is to
      clarify the diagnostic breadth of first-episode psychosis and, on this basis, to
      undertake systematic comparisons across representative populations of the
      psychoses, to include comparisons with first-episode mania. Considered here is
      the new generation of prospective studies that may be able to inform in some way
      on these issues. Attainment of the above goals requires prolonged accrual of
      "all" cases of nonaffective, affective, and any other psychotic illness,
      including first-episode mania, to derive the required representative populations.
      To illustrate some of the challenges, the structure of the Cavan-Monaghan
      prospective first episode study is described and its interim findings are
      outlined, as rural Ireland provides psychiatric care based on strict catchment
      areas and is characterized by substantive ethnic and socioeconomic homogeneity
      and stability. It is argued that there are 3 primary diagnostic nodes
      (schizophrenia spectrum psychosis, bipolar disorder, and major depressive
      disorder with psychotic features) around which there exist numerous additional,
      overlapping, and well-populated diagnostic categories that are distinct only in
      terms of their operational definition. Only through systematic, epidemiologically
      based studies that access this intrinsic diversity are we likely to understand
      fully the origins and pathobiology of first-episode psychosis.

PMID- 15944447
TI  - MSRE-PCR for analysis of gene-specific DNA methylation.
AB  - Abnormal DNA methylation is observed in certain promoters of neoplastic cells,
      although the likelihood of methylation for each individual promoter varies.
      Simultaneous analysis of many promoters in the same sample can allow use of
      statistical methods for identification of neoplasia. Here we describe an assay
      for such analysis, based on digestion of genomic DNA with methylation-sensitive
      restriction enzyme and multiplexed PCR with gene-specific primers (MSRE-PCR).
      MSRE-PCR includes extensive digestion of genomic DNA (uncut fragments cannot be
      identified by PCR), can be applied to dilute samples (<1 pg/microl), requires
      limited amount of starting material (42 pg or genomic equivalent of seven cells)
      and can identify methylation in a heterogeneous mix containing <2% of cells with
      methylated fragments. When applied to 53 promoters of breast cancer cell lines
      MCF-7, MDA-MB-231 and T47D, MSRE-PCR correctly identified the methylation status
      of genes analyzed by other techniques. For selected genes results of MSRE-PCR
      were confirmed by methylation-specific PCR and bisulfite sequencing. The assay
      can be configured for any number of desired targets in any user-defined set of
      genes.

PMID- 15944448
TI  - A complementation method for functional analysis of mammalian genes.
AB  - Our progress in understanding mammalian gene function has lagged behind that of
      gene identification. New methods for mammalian gene functional analysis are
      needed to accelerate the process. In yeast, the powerful genetic shuffle system
      allows deletion of any chromosomal gene by homologous recombination and episomal
      expression of a mutant allele in the same cell. Here, we report a method for
      mammalian cells, which employs a helper-dependent adenoviral (HD-Ad) vector to
      synthesize small hairpin (sh) RNAs to knock-down the expression of an endogenous
      gene by targeting untranslated regions (UTRs). The vector simultaneously
      expresses an exogenous version of the same gene (wild-type or mutant allele)
      lacking the UTRs for functional analysis. We demonstrated the utility of the
      method by using PRPF3, which encodes the human RNA splicing factor Hprp3p.
      Recently, missense mutations in PRPF3 were found to cause autosomal-dominant
      Retinitis Pigmentosa, a form of genetic eye diseases affecting the retina. We
      knocked-down endogenous PRPF3 in multiple cell lines and rescued the phenotype
      (cell death) with exogenous PRPF3 cDNA, thereby creating a genetic
      complementation method. Because Ad vectors can efficiently transduce a wide
      variety of cell types, and many tissues in vivo, this method could have a wide
      application for gene function studies.

PMID- 15944449
TI  - The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair
      of minor groove DNA interstrand crosslinks in mammalian cells produced by the
      pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136.
AB  - SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient
      interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3'
      sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist
      compared to those produced by conventional crosslinking agents such as nitrogen
      mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of
      Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair
      pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to
      their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136
      was >100 times more cytotoxic than melphalan, and the bi-functional agents were
      much more cytotoxic than their respective mono-functional analogues. Cellular
      sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1
      heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The
      relative level of sensitivity of these repair mutant cell lines to SJG-136 was,
      however, significantly less than with major groove crosslinking agents. In
      contrast to melphalan, there was no clear correlation between sensitivity to SJG
      136 and crosslink unhooking capacity measured using a modified comet assay.
      Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA
      double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor
      recognition of DNA damage by repair proteins resulting in the slow repair of both
      mono-adducts and more importantly crosslinks in the minor groove.

PMID- 15944450
TI  - Human Rad51 filaments on double- and single-stranded DNA: correlating regular and
      irregular forms with recombination function.
AB  - Recombinase proteins assembled into helical filaments on DNA are believed to be
      the catalytic core of homologous recombination. The assembly, disassembly and
      dynamic rearrangements of this structure must drive the DNA strand exchange
      reactions of homologous recombination. The sensitivity of eukaryotic recombinase
      activity to reaction conditions in vitro suggests that the status of bound
      nucleotide cofactors is important for function and possibly for filament
      structure. We analyzed nucleoprotein filaments formed by the human recombinase
      Rad51 in a variety of conditions on double-stranded and single-stranded DNA by
      scanning force microscopy. Regular filaments with extended double-stranded DNA
      correlated with active in vitro recombination, possibly due to stabilizing the
      DNA products of these assays. Though filaments formed readily on single-stranded
      DNA, they were very rarely regular structures. The irregular structure of
      filaments on single-stranded DNA suggests that Rad51 monomers are dynamic in
      filaments and that regular filaments are transient. Indeed, single molecule force
      spectroscopy of Rad51 filament assembly and disassembly in magnetic tweezers
      revealed protein association and disassociation from many points along the DNA,
      with kinetics different from those of RecA. The dynamic rearrangements of
      proteins and DNA within Rad51 nucleoprotein filaments could be key events driving
      strand exchange in homologous recombination.

PMID- 15944451
TI  - Excision of formamidopyrimidine lesions by endonucleases III and VIII is not a
      major DNA repair pathway in Escherichia coli.
AB  - Proper maintenance of the genome is of great importance. Consequently, damaged
      nucleotides are repaired through redundant pathways. We considered whether the
      genome is protected from formamidopyrimidine nucleosides (Fapy*dA, Fapy*dG) via a
      pathway distinct from the Escherichia coli guanine oxidation system. The
      formamidopyrimidines are produced in significant quantities in DNA as a result of
      oxidative stress and are efficiently excised by formamidopyrimidine DNA
      glycosylase. Previous reports suggest that the formamidopyrimidine nucleosides
      are substrates for endonucleases III and VIII, enzymes that are typically
      associated with pyrimidine lesion repair in E.coli. We investigated the
      possibility that Endo III and/or Endo VIII play a role in formamidopyrimidine
      nucleoside repair by examining Fapy*dA and Fapy*dG excision opposite all four
      native 2'-deoxyribonucleotides. Endo VIII excises both lesions more efficiently
      than does Endo III, but the enzymes exhibit similar selectivity with respect to
      their action on duplexes containing the formamidopyrimidines opposite native
      deoxyribonucleotides. Fapy*dA is removed more rapidly than Fapy*dG, and duplexes
      containing purine nucleotides opposite the lesions are superior substrates
      compared with those containing formamidopyrimidine-pyrimidine base pairs. This
      dependence upon opposing nucleotide indicates that Endo III and Endo VIII do not
      serve as back up enzymes to formamidopyrimidine DNA glycosylase in the repair of
      formamidopyrimidines. When considered in conjunction with cellular studies [J. O.
      Blaisdell, Z. Hatahet and S. S. Wallace (1999) J. Bacteriol., 181, 6396-6402],
      these results also suggest that Endo III and Endo VIII do not protect E.coli
      against possible mutations attributable to formamidopyrimidine lesions.

PMID- 15944452
TI  - Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase
      I: a functional and molecular dynamics study.
AB  - The functional and dynamical properties of the human topoisomerase I Thr718Ala
      mutant have been compared to that of the wild-type enzyme using functional assays
      and molecular dynamics (MD) simulations. At physiological ionic strength, the
      cleavage and religation rates, evaluated on oligonucleotides containing the
      preferred topoisomerase I DNA sequence, are almost identical for the wild-type
      and the mutated enzymes, as is the cleavage/religation equilibrium. On the other
      hand, the Thr718Ala mutant shows a decreased efficiency in a DNA plasmid
      relaxation assay. The MD simulation, carried out on the enzyme complexed with its
      preferred DNA substrate, indicates that the mutant has a different dynamic
      behavior compared to the wild-type enzyme. Interestingly, no changes are observed
      in the proximity of the mutation site, whilst a different flexibility is detected
      in regions contacting the DNA scissile strand, such as the linker and the V
      shaped alpha helices. Taken together, the functional and simulation results
      indicate a direct communication between the mutation site and regions located
      relatively far away, such as the linker domain, that with their altered
      flexibility confer a reduced DNA relaxation efficiency. These results provide
      evidence that the comprehension of the topoisomerase I dynamical properties are
      an important element in the understanding of its complex catalytic cycle.

PMID- 15944453
TI  - Inferring the connectivity of a regulatory network from mRNA quantification in
      Synechocystis PCC6803.
AB  - A major task of contemporary biology is to understand and predict the functioning
      of regulatory networks. We use expression data to deduce the regulation network
      connecting the sigma factors of Synechocystis PCC6803, the most global regulators
      in bacteria. Synechocystis contains one group 1 (SigA) and four group 2 (SigB,
      SigC, SigD and SigE) sigma factors. From the relative abundance of the sig mRNA
      measured in the wild-type and the four group 2 sigma mutants, we derive a network
      of the influences of each sigma factor on the transcription of all other sigma
      factors. Internal or external stimuli acting on only one of the sigma factors
      will thus indirectly modify the expression of most of the others. From this
      model, we predict the control points through which the circadian time modulates
      the expression of the sigma factors. Our results show that the cross regulation
      between the group 1 and group 2 sigma factors is very important for the
      adaptation of the bacterium to different environmental and physiological
      conditions.

PMID- 15944454
TI  - Metabolic engineering in the -omics era: elucidating and modulating regulatory
      networks.
AB  - The importance of regulatory control in metabolic processes is widely
      acknowledged, and several enquiries (both local and global) are being made in
      understanding regulation at various levels of the metabolic hierarchy. The wealth
      of biological information has enabled identifying the individual components
      (genes, proteins, and metabolites) of a biological system, and we are now in a
      position to understand the interactions between these components. Since phenotype
      is the net result of these interactions, it is immensely important to elucidate
      them not only for an integrated understanding of physiology, but also for
      practical applications of using biological systems as cell factories. We present
      some of the recent "-omics" approaches that have expanded our understanding of
      regulation at the gene, protein, and metabolite level, followed by analysis of
      the impact of this progress on the advancement of metabolic engineering. Although
      this review is by no means exhaustive, we attempt to convey our ideology that
      combining global information from various levels of metabolic hierarchy is
      absolutely essential in understanding and subsequently predicting the
      relationship between changes in gene expression and the resulting phenotype. The
      ultimate aim of this review is to provide metabolic engineers with an overview of
      recent advances in complementary aspects of regulation at the gene, protein, and
      metabolite level and those involved in fundamental research with potential
      hurdles in the path to implementing their discoveries in practical applications.

PMID- 15944457
TI  - The prokaryote-eukaryote dichotomy: meanings and mythology.
AB  - Drawing on documents both published and archival, this paper explains how the
      prokaryote-eukaryote dichotomy of the 1960s was constructed, the purposes it
      served, and what it implied in terms of classification and phylogeny. In doing
      so, I first show how the concept was attributed to Edouard Chatton and the
      context in which he introduced the terms. Following, I examine the context in
      which the terms were reintroduced into biology in 1962 by Roger Stanier and C. B.
      van Niel. I study the discourse over the subsequent decade to understand how the
      organizational dichotomy took on the form of a natural classification as the
      kingdom Monera or superkingdom Procaryotae. Stanier and van Niel admitted that,
      in regard to constructing a natural classification of bacteria, structural
      characteristics were no more useful than physiological properties. They
      repeatedly denied that bacterial phylogenetics was possible. I thus examine the
      great historical irony that the "prokaryote," in both its organizational and
      phylogenetic senses, was defined (negatively) on the basis of structure. Finally,
      we see how phylogenetic research based on 16S rRNA led by Carl Woese and his
      collaborators confronted the prokaryote concept while moving microbiology to the
      center of evolutionary biology.

PMID- 15944455
TI  - Unraveling the secret lives of bacteria: use of in vivo expression technology and
      differential fluorescence induction promoter traps as tools for exploring niche
      specific gene expression.
AB  - A major challenge for microbiologists is to elucidate the strategies deployed by
      microorganisms to adapt to and thrive in highly complex and dynamic environments.
      In vitro studies, including those monitoring genomewide changes, have proven
      their value, but they can, at best, mimic only a subset of the ensemble of
      abiotic and biotic stimuli that microorganisms experience in their natural
      habitats. The widely used gene-to-phenotype approach involves the identification
      of altered niche-related phenotypes on the basis of gene inactivation. However,
      many traits contributing to ecological performance that, upon inactivation,
      result in only subtle or difficult to score phenotypic changes are likely to be
      overlooked by this otherwise powerful approach. Based on the premise that many,
      if not most, of the corresponding genes will be induced or upregulated in the
      environment under study, ecologically significant genes can alternatively be
      traced using the promoter trap techniques differential fluorescence induction and
      in vivo expression technology (IVET). The potential and limitations are discussed
      for the different IVET selection strategies and system-specific variants thereof.
      Based on a compendium of genes that have emerged from these promoter-trapping
      studies, several functional groups have been distinguished, and their
      physiological relevance is illustrated with follow-up studies of selected genes.
      In addition to confirming results from largely complementary approaches such as
      signature-tagged mutagenesis, some unexpected parallels as well as distinguishing
      features of microbial phenotypic acclimation in diverse environmental niches have
      surfaced. On the other hand, by the identification of a large proportion of genes
      with unknown function, these promoter-trapping studies underscore how little we
      know about the secret lives of bacteria and other microorganisms.

PMID- 15944458
TI  - Microbial dextran-hydrolyzing enzymes: fundamentals and applications.
AB  - Dextran is a chemically and physically complex polymer, breakdown of which is
      carried out by a variety of endo- and exodextranases. Enzymes in many groups can
      be classified as dextranases according to function: such enzymes include
      dextranhydrolases, glucodextranases, exoisomaltohydrolases,
      exoisomaltotriohydrases, and branched-dextran exo-1,2-alpha-glucosidases.
      Cycloisomalto-oligosaccharide glucanotransferase does not formally belong to the
      dextranases even though its side reaction produces hydrolyzed dextrans. A new
      classification system for glycosylhydrolases and glycosyltransferases, which is
      based on amino acid sequence similarities, divides the dextranases into five
      families. However, this classification is still incomplete since sequence
      information is missing for many of the enzymes that have been biochemically
      characterized as dextranases. Dextran-degrading enzymes have been isolated from a
      wide range of microorganisms. The major characteristics of these enzymes, the
      methods for analyzing their activities and biological roles, analysis of primary
      sequence data, and three-dimensional structures of dextranases have been dealt
      with in this review. Dextranases are promising for future use in various
      scientific and biotechnological applications.

PMID- 15944456
TI  - Cell wall integrity signaling in Saccharomyces cerevisiae.
AB  - The yeast cell wall is a highly dynamic structure that is responsible for
      protecting the cell from rapid changes in external osmotic potential. The wall is
      also critical for cell expansion during growth and morphogenesis. This review
      discusses recent advances in understanding the various signal transduction
      pathways that allow cells to monitor the state of the cell wall and respond to
      environmental challenges to this structure. The cell wall integrity signaling
      pathway controlled by the small G-protein Rho1 is principally responsible for
      orchestrating changes to the cell wall periodically through the cell cycle and in
      response to various forms of cell wall stress. This signaling pathway acts
      through direct control of wall biosynthetic enzymes, transcriptional regulation
      of cell wall-related genes, and polarization of the actin cytoskeleton. However,
      additional signaling pathways interface both with the cell wall integrity
      signaling pathway and with the actin cytoskeleton to coordinate polarized
      secretion with cell wall expansion. These include Ca(2+) signaling,
      phosphatidylinositide signaling at the plasma membrane, sphingoid base signaling
      through the Pkh1 and -2 protein kinases, Tor kinase signaling, and pathways
      controlled by the Rho3, Rho4, and Cdc42 G-proteins.

PMID- 15944461
TI  - Brain drain.

PMID- 15944462
TI  - Cleaning house.

PMID- 15944463
TI  - Mars and venus.

PMID- 15944460
TI  - Enteric viruses of humans and animals in aquatic environments: health risks,
      detection, and potential water quality assessment tools.
AB  - Waterborne enteric viruses threaten both human and animal health. These pathogens
      are host specific and cause a wide range of diseases and symptoms in humans or
      other animals. While considerable research has documented the risk of enteric
      viruses to human health from contact with contaminated water, the current
      bacterial indicator-based methods for evaluation of water quality are often
      ineffectual proxies for pathogenic viruses. Additionally, relatively little work
      has specifically investigated the risk of waterborne viruses to animal health,
      and this risk currently is not addressed by routine water quality assessments.
      Nonetheless, because of their host specificity, enteric viruses can fulfill a
      unique role both for assessing health risks and as measures of contamination
      source in a watershed, yet the use of animal, as well as human, host-specific
      viruses in determining sources of fecal pollution has received little attention.
      With improved molecular detection assays, viruses from key host groups can be
      targeted directly using PCR amplification or hybridization with a high level of
      sensitivity and specificity. A multispecies viral analysis would provide needed
      information for controlling pollution by source, determining human health risks
      based on assessments of human virus loading and exposure, and determining
      potential risks to production animal health and could indicate the potential for
      the presence of other zoonotic pathogens. While there is a need to better
      understand the prevalence and environmental distribution of nonhuman enteric
      viruses, the development of improved methods for specific and sensitive detection
      will facilitate the use of these microbes for library-independent source tracking
      and water quality assessment tools.

PMID- 15944464
TI  - The longevity gender gap: are telomeres the explanation?
AB  - In this Perspective, we focus on the greater longevity of women as compared with
      men. We propose that, like aging itself, the longevity gender gap is exceedingly
      complex and argue that it may arise from sex-related hormonal differences and
      from somatic cell selection that favors cells more resistant to the ravages of
      time. We discuss the interplay of these factors with telomere biology and
      oxidative stress and suggest that an explanation for the longevity gender gap may
      arise from a better understanding of the differences in telomere dynamics between
      men and women.

PMID- 15944465
TI  - Why females live longer than males: control of longevity by sex hormones.
AB  - Females live longer than males in many species, including humans. We have traced
      a possible explanation for this phenomenon to the beneficial action of estrogens,
      which bind to estrogen receptors and increase the expression of longevity
      associated genes, including those encoding the antioxidant enzymes superoxide
      dismutase and glutathione peroxidase. As a result, mitochondria from females
      produce fewer reactive oxygen species than those from males. Administering
      estrogens has serious drawbacks, however--they are feminizing (and thus cannot be
      administered to males) and may increase the incidence of serious diseases such as
      uterine cancer in postmenopausal women. Phytoestrogens, which are present in soy
      or wine, may have some of the favorable effects of estrogens without their
      undesirable effects. Study of gender differences in longevity may help us to
      understand the basic processes of aging and to devise practical strategies to
      increase the longevity of both females and males.

PMID- 15944466
TI  - Financial planning the first step towards business ownership.

PMID- 15944468
TI  - The ABCs of hepatitis.

PMID- 15944470
TI  - Prediabetes & atherosclerosis: what's the connection?

PMID- 15944472
TI  - Primary care for patients with neurofibromatosis 1.

PMID- 15944474
TI  - Guide to care for patients. Thyroid disorders.

PMID- 15944473
TI  - The spectrum of polypharmacy.

PMID- 15944459
TI  - The TetR family of transcriptional repressors.
AB  - We have developed a general profile for the proteins of the TetR family of
      repressors. The stretch that best defines the profile of this family is made up
      of 47 amino acid residues that correspond to the helix-turn-helix DNA binding
      motif and adjacent regions in the three-dimensional structures of TetR, QacR,
      CprB, and EthR, four family members for which the function and three-dimensional
      structure are known. We have detected a set of 2,353 nonredundant proteins
      belonging to this family by screening genome and protein databases with the TetR
      profile. Proteins of the TetR family have been found in 115 genera of gram
      positive, alpha-, beta-, and gamma-proteobacteria, cyanobacteria, and archaea.
      The set of genes they regulate is known for 85 out of the 2,353 members of the
      family. These proteins are involved in the transcriptional control of multidrug
      efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic
      stress and toxic chemicals, control of catabolic pathways, differentiation
      processes, and pathogenicity. The regulatory network in which the family member
      is involved can be simple, as in TetR (i.e., TetR bound to the target operator
      represses tetA transcription and is released in the presence of tetracycline), or
      more complex, involving a series of regulatory cascades in which either the
      expression of the TetR family member is modulated by another regulator or the
      TetR family member triggers a cell response to react to environmental insults.
      Based on what has been learned from the cocrystals of TetR and QacR with their
      target operators and from their three-dimensional structures in the absence and
      in the presence of ligands, and based on multialignment analyses of the conserved
      stretch of 47 amino acids in the 2,353 TetR family members, two groups of
      residues have been identified. One group includes highly conserved positions
      involved in the proper orientation of the helix-turn-helix motif and hence seems
      to play a structural role. The other set of less conserved residues are involved
      in establishing contacts with the phosphate backbone and target bases in the
      operator. Information related to the TetR family of regulators has been updated
      in a database that can be accessed at www.bactregulators.org.

PMID- 15944475
TI  - OTC at-home defibrillator pros and cons.

PMID- 15944495
TI  - A research study to identify facilitators and barriers to outcome measure
      implementation.
AB  - AIM: To identify facilitators and barriers to implementing outcome measures.
      METHODS: An action-research approach within a hospice and nursing home was used.
      Staff took part in semistructured interviews pre- and post-implementation of the
      Palliative Care Outcome Scale (POS), completed diaries and participated in
      monthly meetings. FINDINGS: Qualitative content analysis identified barriers to
      implementation including: a top-down decision-making approach; outcome measures
      perceived as time-consuming to use; limited resources for data analysis; and a
      lack of knowledge of the importance of outcome measures. Facilitators to
      successful implementation include: involving all staff in decisions about
      implementation; and using a measure that can be adapted to organization needs and
      clinical practice. The benefits of using the measure are rapidly noticeable.
      CONCLUSIONS: Given the need to evaluate services and the role outcome measures
      can have within clinical governance, this article indicates methods by which
      measures may be more successfully implemented.

PMID- 15944496
TI  - End-of-life care in a nursing home: a study of family, nurse and healthcare aide
      perspectives.
AB  - AIM: To examine the perspectives of family members, registered nurses and
      healthcare aides regarding the last 72 hours of Canadian nursing home residents'
      lives. STUDY DESIGN: Exploratory, descriptive design using semistructured
      interviews. SAMPLE: Consisted of 14 registered nurses and eight healthcare aides
      who had provided care within the last 72 hours before a resident's death and four
      family members who had visited within the same time frame. SETTING: A 220-bed
      nursing home located within a larger long-term care facility in Canada. METHODS:
      Thematic analysis was conducted independently and through consensus identified
      themes and subthemes emerging from the interviews. FINDINGS: Dyspnea was a more
      common end-of-life (EoL) symptom for nursing home residents in this sample than
      was pain. Caring behaviours of staff were central to the resident's dying process
      and involved assessment, coordination of care, physical care, family education
      and nurture. Family members' ambivalence about the resident's death and fear of
      the resident dying alone were frequently noted. CONCLUSIONS: Appropriate and
      timely symptom management and a range of caring behaviours of staff are critical
      elements in the dying experience of nursing home residents. Additional education
      and support for personnel involved with caring for this group will enhance end-of
      life care.

PMID- 15944497
TI  - The practice of pilgrimage in palliative care: a case study of Lourdes.
AB  - AIM: To understand why healthcare professionals working in palliative care felt
      that pilgrimage to Lourdes could be a beneficial activity for the terminally ill.
      DESIGN: A qualitative study using a phenomenological framework. METHODS: Nine
      semistructured interviews with a purposive sample of hospice staff. RESULTS: The
      reasons given for accompanying the terminally ill to Lourdes reflected the
      general aims of palliative care. They included improving the quality of life
      through the provision of a holiday, maintaining patient choice and autonomy and
      enabling inner-transformations. The communitas, or altered relationships, formed
      during the pilgrimage were also seen as beneficial.

PMID- 15944498
TI  - Using technology to help obtain the goals of palliative care.

PMID- 15944499
TI  - Bereaved carers' views of a hospice at home service.
AB  - INTRODUCTION: In recent years, there has been an increase in specialist
      palliative care services in the home. Despite this, there have been relatively
      few published evaluations of such care. METHODS: This is a qualitative study
      which used semistructured interviews to explore bereaved carers' views and
      experiences of a hospice at home (HAH) service in the East Midlands, UK. Eleven
      interviews were conducted and analysis followed the framework approach. RESULTS:
      Carers' views were divided into four themes: caring for someone at home; formal
      care provided by HAH; access to out-of-hours care; and provision of specialist
      equipment. CONCLUSIONS: Bereaved carers generally gave very positive accounts on
      care delivered by the HAH service. Shortcomings identified were the provision of
      out-of-hours care and the untimely supply and removal of specialist equipment. It
      is suggested that bereaved carers provide useful insights for qualitative
      evaluations of end-of-life services delivered in the home.

PMID- 15944500
TI  - The increasing use of reiki as a complementary therapy in specialist palliative
      care.
AB  - Palliative medicine and complementary therapies (CTs) have developed within the
      NHS as parallel philosophies of care. As a result, the last decade has seen an
      increase in the integration and usage of CTs, as adjunct therapies to
      conventional medical treatment. Documented benefits of relaxation, decreased
      perception of pain, reduced anxiety and improved sense of wellbeing have been
      shown to enable an enhanced quality of life, where curative treatment is no
      longer an option. Reiki is a more recent addition to the range of CTs available
      to cancer patients. As an energy-healing intervention it has gained in popularity
      as a non-invasive and non-pharmacological approach. Anecdotal evidence suggests
      that the profound relaxation effect has a positive impact on alleviating anxiety,
      stress, perception of pain and promotes a feeling of wellbeing particularly
      relating to the nature of psychospiritual wellbeing. However, there is very
      little evidence to support its application within clinical practice, and none
      within the specific field of specialist palliative care (SPC). This article will
      consider the position of reiki as an emerging CT within SPC. The function of the
      hospice movement, the role of CTs together with an understanding of energy
      healing will also be explored. Within this context, the rise in popularity of
      reiki and its potential benefits for SPC patients will be discussed. These
      considerations will then form the basis of the justification for further research
      in SPC.

PMID- 15944501
TI  - Prevention and management of superficial pressure ulcers.
AB  - Superficial pressure ulcers--those involving the upper layers of skin--are
      currently the object of academic controversy, in particular regarding the
      influence of moisture in their formation. This article aims to steer nurses round
      these debates with a practical approach to preventing pressure damage, placing a
      strong emphasis on skin care and reduction of friction.

PMID- 15944502
TI  - Treatment of a venous leg ulcer with a honey alginate dressing.
AB  - The management of chronic wounds such as venous ulcers is a common and long-term
      issue with the aging population. Non-standard treatment that is both medically
      and financially effective needs to be identified. Honey has been used for its
      healing properties for centuries and has been used to successfully heal wounds
      including pressure-ulcers in our care facility. However, there is not much
      evidence for its use in treating venous ulcers. To this end, I trialed the use of
      a honey-impregnated alginate dressing on a man who had a long-standing history of
      venous ulcers on his leg with the aim of evaluating the effectiveness of honey as
      an alternative treatment to the current wound management therapies. The honey
      seemed to act as an effective antibacterial, anti-inflammatory and deodorizing
      dressing, with total healing of the ulcer achieved. This result, together with
      past successes with the use of honey alginate on ulcerated wounds, has led to
      this product becoming mainstream in the treatment of chronic wounds within our
      care facility.

PMID- 15944503
TI  - Case study detailing treatment of bilateral lower limb lymphoedema.
AB  - Primary lymphoedema is a chronic condition which will continue to worsen if
      treatment is not commenced. Old diagnostic techniques often caused more
      complications and recurrent cellulitis, which damages the superficial lymphatics
      and worsens the condition of the lymphoedema. This article looks at the treatment
      of a person who had a diagnosis for 18 years without treatment as service
      provision was unavailable until recently. It also looks at how quality of life
      and patient empowerment can be improved with simple instructions and an
      appropriate course of treatment.

PMID- 15944505
TI  - Bandages and difficulty with bathing: introducing Seal-Tight.
AB  - Patients with compression bandages experience difficulty with bathing due to the
      possibility that bandages may become wet and affect the wound. Bandage and
      dressing changes resulting from accidental wetting also cost the NHS considerable
      time and money. This product focus highlights the social and psychological impact
      on the patient when they are unable to bathe and offers a solution to the
      problem. Seal-Tight is a product that has been newly placed on the drug tariff,
      making it widely available to all patients who wear bandages (or plaster casts).
      Seal-Tight enables the patient to bathe, in some cases for the first time for
      months or even years.

PMID- 15944506
TI  - Complex wound or complex patient? Strategies for treatment.
AB  - There is no simple definition of what constitutes a complex wound, but in
      practice the term tends to refer wounds with one or more complicating factors,
      e.g. exudate, infection, comorbidity, polypharmacy. Management of complex wounds
      is based on the same principles as non-complex wounds, i.e. holistic assessment
      and addressing the issues identified. This article presents three case studies in
      which these principles are applied.

PMID- 15944508
TI  - A survey of psychological wellbeing in an adult population.
AB  - The British government has called on all NHS staff to help promote good
      psychological wellbeing in the population. This article reports results from a
      survey conducted in Merseyside, England, into the prevalence of poor
      psychological wellbeing across a large part of the region. People registered with
      one of five Merseyside primary care trusts were stratified by age group and
      deprivation, and a questionnaire was mailed to 28,000 who had been randomly
      selected from those aged 15 or over. A total of 11,168 (45%) completed
      questionnaires were returned. Of these, 2,442 (21.9%) respondents rated their
      psychological wellbeing as fairly poor or very poor. Mean levels of psychological
      wellbeing were significantly worse in a number of readily identifiable groups
      within the population, but overall, the lowest wellbeing ratings were
      concentrated in the most socioeconomically deprived quartile. We make a number of
      practical suggestions for the role of the community nurse in promoting good
      psychological wellbeing in patients. We also highlight our finding that
      socioeconomic deprivation was strongly associated with poor psychological
      wellbeing, which was in turn associated with a lifestyle high in risk factors for
      non-communicable diseases.

PMID- 15944509
TI  - Changing indwelling urinary catheters using bladder infill.
AB  - The commonest method used in changing indwelling urinary catheters, either
      urethral or supra-pubic, is to remove the catheter and proceed to re-catheterise.
      When removing the catheter with patients using drainage bags on continual
      drainage, the urinary bladder becomes empty of urine. This may then leave the
      practitioner following re-catheterisation and often with no immediate drainage of
      urine, if the catheter has been safely inserted. A method which the author has
      used for many years and has experienced no problems is re-catheterisation using
      bladder infill. This article explains what is meant by bladder infill and how re
      catheterisation can be undertaken safely using this method.

PMID- 15944510
TI  - Domestic abuse: protection, intervention and the role of the law.
AB  - District nursing sister Gwen Abbot suspects that one of her patients, a 35-year
      old woman who lives with her partner in a rented one bedroom flat, is being
      abused. The woman is reluctant to explain the frequent bruising that is present
      around her arms and breasts when the district nurse visits. Sister Abbot wonders
      if she should get involved and if there were any legal measures the patient could
      take to protect herself from abuse.

PMID- 15944511
TI  - Whistleblowing: it's time to overcome the negative image.
AB  - The media perpetuates the stereotype of the whistleblower forced to go outside
      his or her organization and risk his or her career to bring wrongdoing to public
      awareness. In fact, NHS trusts should all have a whistleblowing policy in place
      which encourages people to raise genuine concerns about wrongdoing, and offer
      protection to those who do this. This article aims to help health workers
      understand the whistleblowing process and so assist them in raising concerns
      within their organization.

PMID- 15944512
TI  - Ellen Seymour: an award winner on a steep learning curve. Interview by Tom
      Pollard.

PMID- 15944513
TI  - Assertiveness: making yourself heard in district nursing.
AB  - Being assertive is not the same as being aggressive. Assertiveness is a tool for
      expressing ourselves confidently, and a way of saying 'yes' and 'no' in an
      appropriate way. This article explores issues concerned with assertiveness in
      district nurse settings. It outlines helpful techniques to develop assertiveness,
      such as the broken record, fogging, negative assertion and negative inquiry.

PMID- 15944514
TI  - A longitudinal study of home care clients and their informal carers.
AB  - The objective of the longitudinal study was to monitor physical and cognitive
      changes in a population of 330 older people being supported at home by health
      services. The participants were 75 years and older and classified as having
      moderate-to-high needs. A total of 210 primary informal carers were recruited to
      determine their specific needs and how they coped as dependency levels of their
      care-recipients changed. Data were collected using six different tools. Two
      questionnaires were mailed out to participating carers. Assessments of care
      recipients were carried out at three sampling points over the study period. The
      clients showed a significant increase in physical dependency and an overall
      increase in cognitive impairment over time. Only 32% of carers lived with care
      recipients, and changes in dependency, cognitive changes, lack of respite and
      performing activities of daily living were all major stressors for informal
      carers. The needs of informal carers are reported and discussed in the context of
      recommendations of the Commission on the Future of Health Care in Canada.

PMID- 15944515
TI  - Make a difference to community nursing.

PMID- 15944516
TI  - [Functional renal reserve and glomerular hyperfiltration].
AB  - The hemodynamic theory of progressive renal disease with glomerular
      hyperfiltration has been proposed as common final pathway of kidney disease
      progression. The evaluation of renal functional reserve is an useful approach to
      point out glomerular hyperfiltration. First the author describes the meaning of
      renal functional reserve, mechanisms of glomerular hemodynamic regulation and
      renal reaction to proteic load and finally explains the practical application of
      renal functional reserve in clinical nephrology.

PMID- 15944517
TI  - Metabolic abnormalities and the medical management of calcium oxalate
      nephrolithiasis.
AB  - The lifetime prevalence of urolithiasis is approximately 12% for men and 7% for
      women in the United States and seems to be increasing; the cost of managing
      kidney stones continues to escalate. The most common kidney stones continue to be
      composed primarily of calcium and are an admixture of phosphate and oxalate. Of
      these, calcium oxalate stones are the most predominant. This review will focus
      only on the pathogenesis and medical management of calcium oxalate stones.

PMID- 15944518
TI  - Ureteroscopic treatment of upper tract urinary calculi.
AB  - Ureteroscopic treatment of upper urinary tract calculi is continuously evolving.
      Initial reports were limited to the treatment of distal ureteral stones. These
      cases had mixed success, and compared to modern ureteroscopy, had significant
      associated morbidity. The entire urinary tract can now be safely accessed via
      ureteroscopy almost always. Improvements in ureteroscope technology have
      certainly made this possible. These advances include smaller steerable scopes and
      sharper optics and video. The enhanced view of the upper urinary tract in
      combination with advances in lithotripsy, in particular, the holmium laser, has
      resulted in increased treatment success and reduced procedure related morbidity.
      This review describes the advances in ureteroscopic technology and provides data
      regarding treatment success and associated complications.

PMID- 15944519
TI  - Anemia and erythropoietin treatment in chronic kidney diseases.
AB  - In patients with renal failure, severe anemia and associated fatigue, cognitive
      and sexual dysfunctions have a significant impact on the quality of life. Anemia
      also represents an important etiological factor in the development of left
      ventricular hypertrophy. An inadequate production of a glycoprotein hormone,
      erythropoietin (EPO), is the major cause of anemia in presence of a reduction in
      the glomerular filtration rate. EPO is the primary regulator of the growth and
      survival of the erythroid progenitor. The treatment of anemia in chronic renal
      failure has been revolutionized by the introduction of recombinant human EPO. The
      vast majority of patients responds very well to treatment, although 5-10% of
      patients shows some resistance to EPO, the most common cause of which is iron
      deficiency. Several studies have recently been started in order to investigate
      the effects of preventing renal anemia from ever developing in uremic patients.
      The hemoglobin concentration target in pre-dialysis and dialysis patients is the
      subject of continuous re-assessment.

PMID- 15944520
TI  - [Nutritional management of patients suffering of chronic renal failure].
AB  - Nutritional support constitutes a fundamental approach to favour the management
      of chronic renal failure and to postpone the need of kidney dialysis. The
      specific goals of the nutrition intervention are: control of protein intake,
      control of phosphate and of calcium intake, control of potassium intake, control
      of energy intake, control of lipid intake with clear identification of the
      polyunsaturated vs monounsaturated vs saturated fatty acid rate, control of
      vitamin intake, prevention of malnutrition and intervention with oral supplements
      or artificial nutrition (even if for short time) if malnutrition occurs. The
      proper management of the nutritional problems of patients with chronic renal
      failure slows the disease progression, prevents or controls symptoms associated
      with uremia and postpones the beginning of substitutive treatment that is of
      hemodialysis or of peritoneal dialysis, thus allowing a better quality of life
      either in the short or long term for patients suffering of chronic renal failure.

PMID- 15944521
TI  - [Unilateral testicular cancer: incidence and effects of a contralateral
      testiculopathy on the sperm output].
AB  - AIM: The aim of this paper was to evaluate the incidence of a non-tumoral,
      contralateral primitive testiculopathy and its relative influence on sperm
      quality of patients with unilateral testicular cancer. METHODS: Twenty-four
      patients (mean age 26 years, range 19-38) with testicular germ cell cancer
      (seminomas, SEM, in 10 cases; nonseminomas, NSEM, in the remaining 14 patients)
      after orchiectomy and before radiotherapy or chemotherapy underwent semen
      analysis, physical examination and scrotal ultrasound of their survivor testis.
      RESULTS: Patients with SEM had sperm concentration, total sperm count and forward
      motility significantly higher than those found in patients with NSEM. Altogether,
      5 out of 24 patients (2 SEM; 3 NSEM) (20.8%) showed azoospermia; 10 patients
      (41.7%) (3 SEM; 7 NSEM) had oligo-, astheno- and/or terato-zoospermia (OAT). The
      remaining 9 patients (37.5%) (5 SEM; 4 NSEM) showed normal sperm parameters. The
      testicular volume of the left over testis was reduced (<12 ml) in 4 out of 5
      (80%) azoospermic patients, in 7 out of 10 patients (70%) of OAT patients, but in
      no patient (0%) with normozoospermia. A testicular biopsy performed on the
      survivor testis of 5 patients with azoospermia (4 of them had a reduced
      testicular volume) confirmed the primitive testiculopathy, showing a histological
      pattern of Sertoli cell syndrome only in 4 of them (80%) and maturation arrest in
      the other case (20%). CONCLUSIONS: Less (OAT) or more severe (azoospermia) sperm
      output impairment in patients with unilateral testicular cancer is associated
      with a coincidental, contralateral to unilateral testicular cancer, primitive
      testiculopathy expressed as reduced testicular volume and impairment
      spermatogenesis at the testicular biopsy.

PMID- 15944522
TI  - [Treatment with non-steroidal anti-inflammatory drugs in patients with amicrobial
      chronic prostato-vesiculitis: transrectal ultrasound and seminal findings].
AB  - AIM: The aim of this paper was to evaluate the efficacy (0= none; 3= fully) of
      the treatment with nonsteroidal anti-inflammatory (NSAI) drugs on (a) gland post
      inflammatory echopattern, by transrectal ultrasound (TRUS); (b) seminal cytologic
      (WBC concentration and spermiophagies) and (c) >2 physicochemical inflammatory
      parameters in patients with chronic amicrobial prostato-vesiculitis (PV).
      METHODS: Thirty-five patients with PV received NSAI drugs in the following
      intermittently steps (over a 3-month period): 1) Pygeum 100 mg twice a day for 14
      consecutive days per month; 2) flavoxate-propyphenazone 400 mg twice a day plus
      Serratiopeptidase 10 000 U twice a day for the subsequent 14 days per month. All
      patients underwent semen analysis and TRUS scans in the pre-treatment and after 3
      months of therapy. RESULTS: The fully (a+b+c) efficacy rate, through an
      improvement of TRUS prostatic or vesicular echopattern in 37.1% and 22.8%
      respectively, was higher than that registered with an improvement of only 1 or 2
      endpoints. Altogether, the following TRUS findings showed reductions (range 25
      40%): prostate volume and hypochogenicity (51.4%); vesicular antero-posterior
      diameter (APD) in the 43.5% and 28.6% of the uni- and bilateral PV respectively;
      vesicular wall tickness (25%); unilateral vesicular honeycomb aspect (36%). No
      efficacy, mainly related to immodified TRUS prostatic or vesicular echopattern in
      51.4% and 65.7% respectively, was observed on: areas of prostatic
      hyperechogenicity; peri-prostatic venous congestion; vesicular APD <7 mm or >21
      mm (with honeycomb aspect). CONCLUSIONS: In PV patients, the treatment with NSAI
      compounds was effective when it was enable to produce multiple positive effects,
      mainly through TRUS changes.

PMID- 15944523
TI  - Wireless capsule endoscopy in the diagnostic of small intestine angiodysplasia in
      chronic uremic patient.
AB  - Gastroenteric bleeding due to angiodysplasia (AD) is a relatively common
      occurrence in patients with end-stage renal failure. Gastric and colon
      angiodysplasic lesions can be easily revealed by endoscopic procedures, whereas
      lesions of the small intestine are more difficult to detect. Imaging modalities
      used in the diagnostic imaging algorithm for the detection of small-bowel AD,
      include non-invasive methods like enema-helical computer tomography,(99m)Tc
      labelled red blood cell scintigraphy, and angiography, and invasive methods such
      as intraoperative enteroscopy. We report the cases of 3 hemodialysis patients
      with recurrent episodes of gastrointestinal bleeding, caused by small-bowel AD
      diagnosed by means of wireless-capsule endoscopy. In all cases, previous
      gastroscopy and colonoscopy were unrevealing. Wireless-capsule endoscopy consists
      in swallowing a capsule endoscope (11 mmx27 mm) which contains a miniature video
      camera, a light source, batteries, and a radio transmitter. Video images are
      transmitted by means of radio telemetry to aerials taped to the body that allow
      images to be captured. Moving images from a period as long as 6 h are stored on a
      portable recorder. Wireless-capsule endoscopy may prove valuable in the
      assessment of gastrointestinal bleeding in uremic patients with unrevealing
      results at gastroscopy and colonoscopy.

PMID- 15944524
TI  - Racial/ethnic disparities in infant mortality--United States, 1995-2002.
AB  - A national health objective for the year 2000 was to reduce the infant mortality
      rate (IMR) in the United States to 7.0 deaths per 1,000 live births among infants
      aged <1 year. The national health objective for 2010 targets a rate of 4.5 infant
      deaths per 1,000 live births; an overarching goal calls for eliminating
      disparities among racial and ethnic populations. To examine racial and ethnic
      disparities in IMRs, data were analyzed from the National Vital Statistics System
      for the period 1995-2002. IMRs were calculated by race/ethnicity of the mother in
      each of the 50 states and the District of Columbia (DC). During 1995-2002, the
      overall IMR in the United States declined from 7.6 infant deaths per 1,000 live
      births in 1995 to 6.8 in 2001, and then increased to 7.0 in 2002. On the basis of
      data for 1995-2002 combined, the target of 4.5 infant deaths per 1,000 live
      births had been achieved by few racial/ethnic populations in few states. To reach
      the target in all racial/ethnic populations, strategies should identify and
      address those factors that contribute to high IMRs and disparities among
      populations.

PMID- 15944525
TI  - Travel-associated dengue infections--United States, 2001-2004.
AB  - Dengue is a mosquito-transmitted, acute viral disease caused by any of the four
      dengue virus serotypes (DEN-1, DEN-2, DEN-3, and DEN-4). Dengue is endemic in
      most tropical and subtropical areas of the world and has occurred in U.S.
      residents returning from travel to such areas. CDC maintains a laboratory-based
      passive surveillance system for travel-associated dengue among U.S. residents.
      The system relies on voluntary reports submitted to state health departments by
      clinicians; patient specimens are then forwarded to CDC for diagnostic testing.
      This report summarizes information about travel-associated dengue cases among
      U.S. residents during 2001-2004. The risk for dengue infection among travelers
      can be reduced by use of repellents and by avoiding exposure to mosquitoes.

PMID- 15944526
TI  - Reporting of chlamydial infection--Massachusetts, January-June 2003.
AB  - Chlamydia trachomatis infection is the most commonly reported sexually
      transmitted disease (STD) in the United States. An estimated 2.8 million
      infections occur annually. In 2002, a total of 834,555 cases in the United
      States, including 10,914 cases in Massachusetts, were reported through the
      National Notifiable Disease Surveillance System (NNDSS). Chlamydial infection is
      most often reported in females, particularly those aged 15-24 years, reflecting a
      higher level of screening in females but also important risk factors. Although
      the majority of infections are asymptomatic, complications are potentially severe
      in women and include pelvic inflammatory disease, which can lead to tubal
      pregnancy, infertility, and chronic pelvic pain. Chlamydial infection during
      pregnancy can cause illness in the infant (e.g., conjunctivitis and pneumonia).
      Infection in men can manifest as urethritis and epididymitis. Timely, documented
      diagnosis and treatment of chlamydial infection are critical to prevent both
      complications and transmission. Since 1996, a progressive increase has occurred
      in the number of reported cases of chlamydial infection in Massachusetts, in part
      because of an increase in screening and use of more sensitive tests. This report
      summarizes an evaluation of chlamydial-infection reporting in Massachusetts
      during January-June 2003. The results underscore the need for improvement in both
      completeness and timeliness of reporting chlamydial infection in Massachusetts.

PMID- 15944527
TI  - Fraud in medicine.

PMID- 15944528
TI  - The atherosclerotic plaque: a healthy challenge to the limits of nuclear imaging.

PMID- 15944529
TI  - Transient ischemic dilation associated with poststress myocardial stunning of the
      left ventricle in vasodilator stress myocardial perfusion SPECT: true marker of
      severe ischemia?

PMID- 15944530
TI  - High-resolution molecular imaging techniques for cardiovascular research.

PMID- 15944531
TI  - Relationship of transient ischemic dilation in dipyridamole myocardial perfusion
      imaging and stress-induced changes of functional parameters evaluated by Tl-201
      gated SPECT.
AB  - BACKGROUND: This study assessed whether transient ischemic dilation (TID) of the
      left ventricle is related to ischemic stunning, manifested by stress-induced
      decrease of left ventricular ejection fraction (LVEF) and worsening of wall
      motion, by use of dipyridamole-stress and redistribution thallium 201 gated
      single photon emission computed tomography (SPECT). METHODS AND RESULTS: Ninety
      two consecutive patients undergoing dipyridamole Tl-201 gated SPECT were
      included. Patients with a TID ratio in the highest quartile were defined as
      having TID. In patients with TID, end-diastolic volume (EDV) and end-systolic
      volume (ESV) were both significantly greater on dipyridamole-stress images than
      on redistribution images (P < .001). The degree of enlargement was much greater
      for ESV than EDV. In patients without TID, EDV and ESV were both decreased after
      stress (P < .001). Patients with TID had a lower mean LVEF on dipyridamole-stress
      images than on redistribution images (P < .001). Patients without TID had a
      higher mean LVEF on dipyridamole-stress images than on redistribution images (P <
      .001). Patients with TID had a significant worsening of global wall motion on
      dipyridamole-stress images than on redistribution images (P < .001), but patients
      without TID did not. CONCLUSION: TID was significantly correlated with ischemic
      stunning, and the enlargement of ESV was an important factor resulting in TID.

PMID- 15944532
TI  - Prognostic value of adenosine Tl-201 myocardial perfusion imaging after acute
      myocardial infarction: results of a prospective clinical trial.
AB  - BACKGROUND: We have previously shown in retrospective studies that adenosine
      myocardial perfusion imaging (MPI) done after acute myocardial infarction (AMI)
      can effectively predict the risk of future cardiac events in these patients. The
      objective of this study was to validate these observations in a prospective
      clinical trial. METHODS AND RESULTS: One hundred twenty-six stable patients
      underwent quantitative adenosine MPI at a mean of 4.5 +/- 2.9 days after AMI. On
      the basis of the MPI results, they were divided into 3 risk groups: low risk (<
      20% perfusion defect), intermediate risk (> or = 20% perfusion defect with < 10%
      ischemia), and high risk (> or = 20% perfusion defect with > 10% ischemia). The
      patients were followed up for 11 +/- 5 months for the occurrence of cardiac
      events: death, myocardial infarction, unstable angina, or congestive heart
      failure. The actual event rates correlated very well with the prespecified risk
      groups (19% for the low-risk group, 28% for the intermediate-risk group, and 78%
      for the high-risk group; P < .001). The significant multivariate predictors for
      events were female gender (relative risk [RR], 2.90; P = .002), left ventricular
      ejection fraction (RR, 1.34; P = .04), and ischemic defect size (RR, 1.46; P =
      .001), with a global chi2 value of 26.7. CONCLUSION: This study demonstrates, in
      a prospectively designed clinical trial, that quantitative adenosine MPI
      performed soon after AMI can effectively predict the risk of future cardiac
      events. These findings are currently being validated in an ongoing, large,
      multicenter, international clinical trial.

PMID- 15944533
TI  - Myocardial perfusion SPECT reconstruction: receiver operating characteristic
      comparison of CAD detection accuracy of filtered backprojection reconstruction
      with all of the clinical imaging information available to readers and solely
      stress slices iteratively reconstructed with combined compensation.
AB  - BACKGROUND: Past receiver operating characteristic (ROC) studies have
      demonstrated that single photon emission computed tomography (SPECT) perfusion
      imaging by use of iterative reconstruction with combined compensation for
      attenuation, scatter, and detector response leads to higher area under the ROC
      curve (A(z)) values for detection of coronary artery disease (CAD) in comparison
      to the use of filtered backprojection (FBP) with no compensations. A new ROC
      study was conducted to investigate whether this improvement still holds for
      iterative reconstruction when observers have available all of the imaging
      information normally presented to clinical interpreters when reading FBP SPECT
      perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50
      patients referred for angiography and 37 patients with a lower than 5% likelihood
      for CAD were included in the ROC study. The images from the two methods were read
      by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the
      FBP readings were the short-axis, horizontal long-axis, and vertical long-axis
      slices for both the stress and rest images; cine images of both the stress and
      rest projection data; cine images of selected cardiac-gated slices; the CEQUAL
      generated stress and rest polar maps; and an indication of patient gender. This
      was compared with reading solely the iterative reconstructed stress slices with
      combined compensation for attenuation, scatter, and resolution. With A(z) as the
      criterion, a 2-way analysis of variance showed a significant improvement in
      detection accuracy for CAD for the 7 observers (P = .018) for iterative
      reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even
      with the additional imaging information provided to the observers when scoring
      the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending
      physicians or 4 cardiology fellows were compared separately, the iterative
      technique was not statistically significantly better; however, the A(z) for each
      of the 7 observers individually was larger for iterative reconstruction than for
      FBP. Compared with results from our previous studies, the additional imaging
      information did increase the diagnostic accuracy of FBP for CAD but not enough to
      undo the statistically significantly higher diagnostic accuracy of iterative
      reconstruction with combined compensation. CONCLUSIONS: We have determined
      through an ROC investigation that included two classes of observers (experienced
      attending physicians and cardiology fellows in training) that iterative
      reconstruction with combined compensation provides statistically significantly
      better detection accuracy (larger A(z)) for CAD than FBP reconstructions even
      when the FBP studies were read with all of the extra clinical nuclear imaging
      information normally available.

PMID- 15944534
TI  - Noninvasive in vivo measurement of vascular inflammation with F-18
      fluorodeoxyglucose positron emission tomography.
AB  - BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) has been shown to accumulate in
      inflamed tissues. However, it is not known whether vascular inflammation can be
      measured noninvasively. The aim of this study was to test the hypothesis that
      vascular inflammation can be measured noninvasively by use of positron emission
      tomography (PET) with FDG. METHODS AND RESULTS: Inflamed atherosclerotic lesions
      were induced in 9 male New Zealand white rabbits via balloon injury of the
      aortoiliac arterial segment and exposure to a high cholesterol diet. Ten rabbits
      fed standard chow served as controls. Three to six months after balloon injury,
      the rabbits were injected with FDG (1 mCi/kg), after which aortic uptake of FDG
      was assessed (3 hours after injection). Biodistribution of FDG activity within
      aortic segments was obtained by use of standard well gamma counting. FDG uptake
      was also determined noninvasively in a subset of 6 live atherosclerotic rabbits
      and 5 normal rabbits, via PET imaging and measurement of standardized uptake
      values over the abdominal aorta. Plaque macrophage density and smooth muscle cell
      density were determined by planimetric analysis of RAM-11 and smooth muscle actin
      staining, respectively. Biodistribution of FDG within nontarget organs was
      similar between atherosclerotic and control rabbits. However, well counter
      measurements of FDG uptake were significantly higher within atherosclerotic
      aortas compared with control aortas (P < .001). Within the upper abdominal aorta
      of the atherosclerotic group (area of greatest plaque formation), there was an
      approximately 19-fold increase in FDG uptake compared with controls (108.9 +/-
      55.6 percent injected dose [%ID]/g x 10(3) vs 5.7 +/- 1.2 %ID/g x 10(3) [mean +/-
      SEM], P < .001). In parallel with these findings, FDG uptake, as determined by
      PET, was higher in atherosclerotic aortas (standardized uptake value for
      atherosclerotic aortas vs control aortas, 0.68 +/- 0.06 vs 0.13 +/- 0.01; P <
      .001). Moreover, macrophage density, assessed histologically, correlated with
      noninvasive (PET) measurements of FDG uptake (r = 0.93, P < .0001). In contrast
      to this finding, FDG uptake did not correlate with either aortic wall thickness
      or smooth muscle cell staining of the specimens. CONCLUSION: These data show that
      FDG accumulates in macrophage-rich atherosclerotic plaques and demonstrate that
      vascular macrophage activity can be quantified noninvasively with FDG-PET. As
      such, measurement of vascular FDG uptake with PET holds promise for the
      noninvasive characterization of vascular inflammation.

PMID- 15944535
TI  - Detecting changes in serial myocardial perfusion SPECT: a simulation study.
AB  - BACKGROUND: New algorithms were evaluated for their efficacy in detecting and
      quantifying serial changes in myocardial perfusion from single photon emission
      computed tomography (SPECT). METHODS AND RESULTS: We generated 72 simulations
      with various left ventricular positions, sizes, count rates, and perfusion defect
      severities using the nonuniform rational B-splines (NURBs)-based CArdiac Torso
      (NCAT) phantom. Images were automatically aligned by use of both full linear and
      rigid transformations and quantified for perfusion by use of the CEqual program.
      Changes within a given perfusion defect were compared by use of a Student t test
      before and after registration. Registration approaches were compared by use of
      receiver operating characteristic analysis. Changes of 5% were not detected well
      in single patients with or without alignment. Changes of 10% and 15% could be
      detected with false-positive rates of 15% and 10%, respectively, in single
      studies if alignment was performed before perfusion analysis. Alignment also
      reduced the number of studies necessary to demonstrate a significant perfusion
      change (P < .05) in groups of patients by about half. CONCLUSION: Comparison of
      mean uptake by t values in SPECT perfusion defects can be used to detect 10% and
      greater differences in serial perfusion studies of single patients. Image
      alignment is necessary to optimize automatic detection of perfusion changes in
      both single patients and groups of patients.

PMID- 15944536
TI  - An improved model for the measurement of myocardial perfusion in human beings
      using N-13 ammonia.
AB  - BACKGROUND: Oxygen 15 water and nitrogen 13 ammonia are widely used for the
      quantitative measurement of myocardial perfusion with positron emission
      tomography. However, blood flow obtained with N-13 ammonia by use of the
      conventional 2-compartment model frequently underestimates flow by 30% to 50%
      compared with O-15 water. We hypothesized that this discrepancy is a result of
      the model configuration of N-13 ammonia and investigated changes to the
      mathematical model to determine whether more accurate measurements of perfusion
      could be obtained. METHODS AND RESULTS: Twelve healthy volunteers were
      sequentially studied with O-15 water and N-13 ammonia at rest and during maximal
      coronary vasodilation with adenosine. Perfusion measurements obtained with the
      conventional and modified models were compared with values obtained with O-15
      water. The conventional N-13 ammonia model underestimated flow by 37% +/- 16% at
      rest and by 20% +/- 24% with stress when compared with flows obtained with O-15
      water. The modified model yielded flow values closer to the line of identity than
      the conventional model (y = 1.07x + 0.04 vs y = 0.69x + 0.08; respectively; P <
      .01). CONCLUSIONS: Model changes made N-13 ammonia myocardial blood flow
      estimates more comparable to those obtained with O-15 and may allow for better
      comparison of flows obtained with these two tracers in the future. Further
      efforts are warranted to evaluate the accuracy of flow models in human subjects.

PMID- 15944537
TI  - Myocardial perfusion SPECT imaging in patients with myocardial bridging.
AB  - BACKGROUND: Although myocardial perfusion single photon emission computed
      tomography (SPECT) imaging is widely used to assess myocardial ischemia in
      patients with known or suspected coronary artery disease, only a few patients
      with myocardial bridging have been evaluated with nuclear techniques.
      Furthermore, it has been suggested that dipyridamole stress images might
      underestimate perfusion defects compared with exercise stress images. This study
      was done to determine the concordance of exercise stress SPECT images with that
      obtained by dipyridamole stress SPECT images as a means of detecting ischemia in
      patients with myocardial bridging. METHODS AND RESULTS: Sixteen consecutive
      patients with angina and normal arteries but myocardial bridging of the left
      anterior descending artery underwent rest-exercise stress SPECT imaging. Within 2
      weeks after angiograms were obtained, only dipyridamole stress images were
      repeated. The mean angiographic systolic occlusion within the myocardial bridges
      was 73% +/- 10%. Overall, the prevalence of an abnormal scan was no different in
      patients who underwent exercise stress myocardial perfusion imaging (MPI) as
      compared with patients who underwent dipyridamole stress MPI (14/16 [88%] vs
      13/16 [81%], respectively; P = .953). Exercise stress MPI showed a higher stress
      score than dipyridamole stress MPI, but the difference did not reach statistical
      significance (7.5 +/- 3.3 vs 6 +/- 2.7, P = .147). The strength of agreement
      among exercise stress MPI and dipyridamole stress MPI studies was good (kappa =
      0.765; 95% CI, 0.318 to 1.211; P < .05). CONCLUSIONS: Cardiac SPECT studies can
      be used effectively for assessing ischemia in patients with angina and myocardial
      bridging. The evaluation of myocardial perfusion with dipyridamole stress SPECT
      imaging showed a good agreement with exercise stress SPECT imaging for the
      detection of ischemia in this group of patients.

PMID- 15944538
TI  - Cardiovascular magnetic resonance: structure, function, perfusion, and viability.

PMID- 15944539
TI  - Cardiovascular magnetic resonance imaging of coronary atherothrombosis.

PMID- 15944541
TI  - Focal uptake of radioactive tracer in the mediastinum during SPECT myocardial
      perfusion imaging.

PMID- 15944542
TI  - Cardiogenic shock after dipyridamole administration for myocardial perfusion
      imaging.

PMID- 15944540
TI  - Imaging of myocardial metabolism.
AB  - There is compelling evidence that alterations in myocardial substrate use play a
      key role in a variety of normal and abnormal cardiac conditions such as aging,
      left ventricular hypertrophy, and diabetic heart disease. However, it is unclear
      whether the metabolic changes are adaptive or maladaptive. Development of
      transgenic models targeting key aspects of myocardial substrate use, such as
      uptake, oxidation, and storage, is accelerating our understanding of the
      metabolic perturbations of cardiac disease. However, whether the metabolic
      phenotype in these models is relevant to the human condition is frequently
      unknown. The importance of altered myocardial metabolism in the pathogenesis of
      cardiac disease is underscored by the current robust development of novel
      therapeutics that target myocardial substrate use. Currently, magnetic resonance
      spectroscopy, single photon emission computed tomography, and positron emission
      tomography are the 3 methods available to image myocardial substrate metabolism.
      In this review the role of metabolic imaging in the study of specific cardiac
      disease processes will be discussed. Both the current and future capabilities of
      metabolic imaging to furthering our understanding of cardiac disease are
      highlighted.

PMID- 15944544
TI  - President's message: Freedom of medical imaging: the Medicare Payment Advisory
      Commission's recommendations to Congress.

PMID- 15944547
TI  - Implementation of duty hour standards in otolaryngology-head and neck surgery
      residency training.
AB  - OBJECTIVE: To determine what impact, if any, of the recently implemented duty
      hour standards have had on otolaryngology-head and neck surgery residency
      programs from the perspective of program directors. We hypothesized that the
      implementation of resident duty hour limitations have caused changes in
      otolaryngology training programs in the United States. STUDY DESIGN AND SETTING:
      Information was collected via survey in a prospective, blinded fashion from
      program directors of otolaryngology-head and neck residency training programs in
      the United States. RESULTS: Overall, limitation of resident duty hours is not an
      improvement in otolaryngology-head and neck residency training according to 77%
      of the respondents. The limitations on duty hours have caused changes in the
      resident work schedules in 71% of the programs responding. Approximately half of
      the residents have a favorable impression of the work hour changes. Thirty-two
      percent of the respondents indicate that changes to otolaryngology support staff
      were required, and of those many hired physician assistants. Eighty-four percent
      of the respondents did not believe that the limitations on resident duty hours
      improved patient care, and 81% believed that it has negatively impacted resident
      training experience. Forty-five percent of the program directors felt that
      otolaryngology-head and neck faculty were forced to increase their work loads to
      accommodate the decrease in the time that residents were allowed to be involved
      in clinical activities. Fifty-four percent of the programs changed from in
      hospital to home call to accommodate the duty hour restrictions. CONCLUSIONS:
      According to the majority of otolaryngology-head and neck surgery program
      directors who responded to the survey, the limitations on resident duty hours
      imposed by the ACGME are not an improvement in residency training, do not improve
      patient care, and have decreased the training experience of residents.
      SIGNIFICANCE: This study demonstrates that multiple changes have been made to
      otolaryngology-head and neck surgery training programs because of work hour
      limitations set forth by the ACGME.

PMID- 15944548
TI  - Satisfaction and gender issues in otolaryngology residency.
AB  - OBJECTIVE: To evaluate the otolaryngology residency experience with attention to
      operative experience, career guidance, and gender. STUDY DESIGN AND SETTING:
      Otolaryngology residents were anonymously surveyed by mail about their residency
      experience. The 22-item survey was scored on a 5-point ordinal Likert scale.
      Responses were analyzed with respect to gender and postgraduate year (PGY) level.
      RESULTS: Complete surveys were returned by 261 otolaryngology residents (24%
      female). PGY level correlated with confidence that surgical skills were
      appropriate (P = 0.003), establishment of solid career network (P = 0.003), and
      confidence that surgical abilities are adequate for practice (P = 0.028). Female
      residents reported less confidence that surgical skills were appropriate (P =
      0.050) and that surgical abilities were adequate for postresidency practice (P =
      0.035). Women were encouraged to enter private practice more often (P = 0.012),
      were less likely to have a solid career network ( P = 0.025), and were less
      confident about being able to run their own practice (P = 0.036) CONCLUSIONS:
      Significant differences exist for several questions regarding surgical confidence
      and career issues, even after correction for PGY level.

PMID- 15944549
TI  - Successful outpatient treatment of sinusitis exacerbations caused by community
      acquired methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: To determine whether community-acquired MRSA sinusitis can be
      adequately treated on an outpatient basis without the need for intravenous
      antibiotics. STUDY DESIGN AND SETTING: Retrospective review of all cases of
      community-acquired MRSA sinusitis encountered by the author over a 36-month
      period. RESULTS: Of 29 patients who tested positive for MRSA sinusitis, 26
      patients had follow-up information available and were retrospectively reviewed.
      The average follow-up period was 12.0 months (range: 1-36 mo). Twelve infectious
      episodes of MRSA were treated with oral antibiotics alone and 16 were treated
      with a combination of oral and topical antibiotics. The mean time to clinical
      resolution with these regimens was 5.7 weeks (range: 3-8 wks). Two patients
      experienced recurrent MRSA infections resulting in a recurrence rate of 7.7% and
      an overall resolution rate of 92.3%. CONCLUSIONS: Community-acquired MRSA
      sinusitis can be very adequately treated on an outpatient basis with culture
      directed oral and topical antibiotics.

PMID- 15944550
TI  - Tissue model and preliminary analysis of microdebriders used in functional
      endoscopic sinus surgery.
AB  - OBJECTIVE: To develop a standardized in vitro tissue model for microdebrider
      comparison, and determine which microdebrider, tissue type, blade type, and
      suction strength is most efficient. STUDY DESIGN AND SETTING: A prospective
      randomized comparison of the Diego Powered Dissector and XPS 3000 Powered ENT
      System was conducted using a soft-tissue and a firm-tissue model. In addition to
      evaluating tissue aspiration with straight and angled blades, clogging rates and
      clearance times were measured. Both standard wall suction and liposuction were
      used. Basic statistical analysis and a one-way analysis of variance using
      confidence intervals were performed to compare outcomes. RESULTS: The aspiration
      of soft tissue was statistically superior to and demonstrated less clogging
      compared to the aspiration of firm tissue. For the "head-to-head" comparison, the
      XPS 3000 was statistically superior for aspirating soft tissue. When liposuction
      was excluded, the devices were essentially equivalent. Several notable trends
      that were not statistically significant were also observed. The aspiration
      efficiency of straight blades appeared to be superior compared to angled blades.
      The XPS 3000 and liposuction independently seemed to aspirate more tissue than
      the Diego Powered Dissector and regular suction, but at the expense of increased
      clogging. Finally, the Diego Powered Dissector showed a trend toward aspirating
      more firm tissue. CONCLUSION: Our tissue model represents a reliable and
      reproducible means of microdebrider comparison. A secondary analysis with a
      larger sample size is warranted to further validate the tissue model, to improve
      the power of the statistically significant results, and to better delineate the
      trends that were observed in the current study.

PMID- 15944551
TI  - Papillary and follicular variant of papillary carcinoma of the thyroid: Initial
      presentation and response to therapy.
AB  - INTRODUCTION: The 2 most common histologic variants of papillary carcinoma are
      pure papillary carcinoma (PTC) and follicular variant of papillary thyroid
      carcinoma (FVPTC). The purpose of this study is to compare the presentation and
      short-term response to therapy of these variants and to determine if FVPTC is a
      more aggressive form of thyroid cancer that warrants intensive therapy. METHODS:
      A retrospective chart review of patients treated for PTC and FVPTC between 1996
      and 1999 was performed. Clinical variables were compared with the Wilcoxon Rank
      Sum test or the Fischer's Exact Test. RESULTS: Of 160 patients with papillary
      thyroid carcinoma included, 114 (71%) had PTC and 46 (29%) had FVPTC. Mean follow
      up was 38.6 months. FVPTC presented with larger tumors (median 1.5 cm vs 1.0 cm,
      P = 0.007) and higher tumor stage than PTC. PTC patients were more likely to
      present with local invasion and to have local recurrence (9.65% vs 0% for both
      variables). There were no significant differences in patient age, gender,
      vascular invasion, lymph node or distant metastases, surgical treatment,
      radioactive iodine therapy, remission, or mortality. CONCLUSION: FVPTC presented
      with larger original tumor size and higher tumor stage but a lower local invasion
      rate and recurrence rate than patients with PTC despite similar therapies. These
      data suggest that FVPTC and PTC carry similar prognoses in early stages and that
      FVPTC may have a reduced predilection for local invasion. Although further
      studies with longer follow-up are required, these results do not suggest that
      FVPTC warrants more aggressive therapy than PTC.

PMID- 15944552
TI  - Preoperative radiation therapy and its effects on outcomes in microsurgical head
      and neck reconstruction.
AB  - OBJECTIVE: Preoperative radiation therapy is considered a significant factor in
      head and neck reconstruction. STUDY AND DESIGN AND SETTING: In our consecutive
      series of 114 patients, 44 patients had prior head and neck irradiation. The 2
      groups were compared on the basis of age, ischemic time, and flap size and were
      found not to be statistically different. The average ischemic time for the
      irradiated group was 94.1 minutes, and the average was 102.8 minutes for the
      nonirradiated group. The average flap size for the irradiated group was 69.5 cm 2
      and was 72.0 cm 2 for the nonirradiated group. RESULTS: Using a single-factor
      analysis of variance, the 2 groups did not differ statistically. The overall
      major flap complication rate for both irradiated and nonirradiated groups was
      approximately 10%. CONCLUSION: Microvascular reconstruction was accomplished in
      both irradiated and nonirradiated head and neck patients, with a 99% total flap
      survival rate and a 10% major flap complication rate.

PMID- 15944553
TI  - The surgical approach to retrosternal goiters: the role of computerized
      tomography.
AB  - OBJECTIVE: To assess preoperative CT scans of patients with a retrosternal
      goiter, with an objective of identifying features that are likely to predict the
      need for sternotomy at operation. STUDY DESIGN AND SETTING: A retrospective
      review of clinical notes and CT scans of patients who underwent thyroidectomy for
      retrosternal goiter at a large district general hospital in the United Kingdom
      between 1998 and 2002. RESULTS: Extension of the goiter to the level of the
      aortic arch, particularly when combined with tracheal involvement or major vessel
      displacement, increases the likelihood of requiring median sternotomy.
      CONCLUSIONS: Most retrosternal goiters can be approached through a cervical
      incision alone. However, extension of the goiter to the level of the aortic arch
      does appear to increase the likelihood of requiring sternotomy. SIGNIFICANCE: In
      such cases in which sternotomy is anticipated, the availability of cardiothoracic
      services would be helpful to avoid patient morbidity.

PMID- 15944554
TI  - Pattern of regional metastases from cutaneous squamous cell carcinoma of the head
      and neck.
AB  - OBJECTIVE: To assess the pattern of regional metastases from SCC of the skin of
      the head and neck as a prognostic factor. STUDY DESIGN AND SETTING: A
      retrospective chart review of 22 patients treated in a tertiary academic center.
      RESULTS: Metastases could be assessed clinically in the parotid gland and the
      neck in 50% and 59% of the patients, respectively. Histologic examination showed
      metastases in the parotid gland and the neck in 68% and 45.5%, respectively.
      Occult disease was 36% and 20% in the parotid gland and neck, respectively. The
      1st echelon for metastasis was the parotid gland lymph nodes, whereas level II
      lymph nodes were the 1st echelon in the neck. Metastases to both the parotid
      gland and neck decreased the overall survival to 0, compared with 60% for
      metastases to the parotid gland and 100% for the neck. CONCLUSIONS: SCC of the
      skin of the head and neck with regional metastases has a high incidence of occult
      metastases in the parotid gland and the neck. Patients with metastases in both
      sites have a poor prognosis.

PMID- 15944555
TI  - Laser carbon dioxide cordectomy versus open surgery in the treatment of glottic
      carcinoma: our results.
AB  - OBJECTIVE: To analyze oncologic results in patients with glottic cancers treated
      respectively, by laser CO 2 or open surgery, taking into account specific-disease
      survival, rate of locoregional recurrences, and their salvageability. STUDY
      DESIGN: Retrospective study of 198 patients treated from January 1993 to June
      2002 in the department of otorhinolaryngology at a Catholic university in Rome.
      METHODS: Glottic carcinoma were treated by laser CO 2 cordectomy in 132 patients
      (group 1) and by open surgery in 66 patients (group 2). The statistical analysis
      was performed by Kaplan Meyer method, log rank test, and chi 2 test. RESULTS: The
      log-rank test points out significant differences between the 2 groups regarding
      specific-disease survival; no differences were found for disease-free survival.
      Within group 1, 16 patients developed local failure, which was retreated in 6
      cases with laser surgery; in 9 (6.8%) with total laryngectomy, only 1 case was
      inoperable. In this group, 10 patients (62.5%) were salvaged. Within group 2, 18
      patients developed local recurrences, which was retreated in 14 (21.21%) cases
      with total laryngectomy; the other 4 cases were not suitable for surgery. Of
      these 18, 8 patients (44.5%) were salvaged. CONCLUSIONS AND SIGNIFICANCE: Our
      results show significant differences between the 2 groups concerning the specific
      disease survival and the salvageability of local recurrences. In fact, in group 1
      we found a higher salvage rate and a lower incidence of total laryngectomy. As
      already suggested, laser therapy leaves the laryngeal cartilaginous framework
      intact, avoiding the spread of the tumor out of laryngeal organ and resulting in
      a more favorable oncologic outcome.

PMID- 15944556
TI  - Treatment results on advanced neck metastasis (N3) from head and neck squamous
      carcinoma.
AB  - OBJECTIVE: To analyze the long-term results of patients with N3 neck metastasis
      from squamous carcinoma of the head and neck. STUDY DESIGN: This study is based
      on the analysis of a retrospective cohort of 224 previously untreated patients
      with squamous cell carcinoma of the head and neck and lymph node metastasis sized
      greater than 6 cm (N3) who were evaluated from 1981 to 1996. RESULTS: Fifty-four
      patients (24.1%) underwent neck dissection, 137 underwent radiotherapy alone
      (61.2%), and 33 received only supportive care (14.7%). Control of the neck
      metastasis was achieved in 46 cases among the treated ones (24.1%), varying from
      51.9% for the patients who underwent surgery to 13.1% for radiotherapy alone ( P
      < 0.001). Exclusive distant metastasis occurred in 37.0% of the cases who had
      control of the neck disease. The 3-year overall survival rates were 17.9% for
      patients who underwent surgery and 7.0% for radiotherapy alone ( P = 0.003). The
      multivariate analysis showed as independent predictive factors the treatment
      approach ( P < 0.001) and tumor site ( P = 0.016). CONCLUSIONS: This study
      confirms the poor prognosis of patients with N3 neck disease, mainly when treated
      by radiotherapy alone. A radical neck dissection associated with adjuvant
      radiotherapy is indicated whenever feasible. Because of the high rate of distant
      metastasis, protocols including adjuvant chemotherapy should be investigated.

PMID- 15944557
TI  - Prognostic significance of stromal eosinophilic infiltration in cancer of the
      larynx.
AB  - OBJECTIVE: To investigate prevalence and possible role of tumor-associated tissue
      eosinophilia (TATE) as a prognostic factor in laryngeal squamous cell cancer.
      STUDY DESIGN: Prospective case series. METHODS: Seventy-eight consecutive
      patients with diagnosis of squamous cell carcinoma of the larynx and who were
      treated surgically in our center were evaluated. The possible role of TATE as a
      prognostic factor in laryngeal squamous cell cancer was investigated with respect
      to tumor differentiation, depth of invasion, perineural and vascular invasion
      (histopathological parameters), and neck metastasis (clinical parameter). The
      relation between presence of TATE and age was also examined. RESULTS: TATE was
      positive in the tumors of 32% of the patients, including low grade, 20 (26%);
      medium grade, 4 (5%); and high grade, 1 (1%). The relationships between TATE and
      tumor differentiation, perineural invasion, vascular invasion, pathologic N
      stage, and depth of invasion were not statistically significant ( P > 0.05).
      According to Spearman correlation analysis ( r = -0.383, P = 0.001), there is a
      negative correlation between TATE and age. Ages of TATE-positive patients tend to
      be clustered in the 5th and 6th decades of life, whereas the TATE-negative
      patients' ages tend to be clustered in the 6th and 7th decades. CONCLUSIONS: TATE
      has no correlation with prognostic parameters in laryngeal squamous cell cancer.
      Presence of TATE is highly correlated with age. Incidence of TATE is very low
      over the age of 60 years, and this may suggest that age influences the tissue
      inflammatory response to tumor. Further investigation is needed to explain the
      associations of TATE and age and also the host response to malignancy.

PMID- 15944558
TI  - Thyroid nodules: evaluation with power Doppler and duplex Doppler ultrasound.
AB  - This study purposes a new classification of thyroid nodules blood flow by power
      duplex Doppler ultrasound. A total of 177 nodules were studied with B-mode
      scanning, power Doppler, and spectral analysis. These data were compared with
      cytological results from ultrasound-guided fine-needle aspiration biopsy.
      Univariate and multivariate logistic regression analysis were performed. The
      power Doppler analysis of the nodules produced 5 vascular patterns: I, absence of
      signal blood flow; II, exclusively perinodular blood flow; III, perinodular >/=
      central blood flow; IV, central blood flow > perinodular blood flow; V,
      exclusively central blood flow. Statistical analysis revealed a significant
      relationship between these vascular patterns and cytological results. The
      spectral analysis demonstrated that the resistance index were higher in nodules
      with malignant versus other cytology ( P < 0.001). The results indicate that
      power duplex Doppler facilitates screening of thyroid nodules at high risk for
      malignancy with elevated sensitivity (92.3%) and specificity (88%).

PMID- 15944559
TI  - Evaluation of botulinum toxin A in treatment of tinnitus.
AB  - OBJECTIVES: The purpose of this study was to evaluate the potential benefit of
      botulinum toxin A in treatment of tinnitus with a prospective, double-blinded
      study design. STUDY DESIGN: Double-blinded, prospective clinical study. METHODS:
      Thirty patients with tinnitus were randomly placed into 1 of 2 treatment arms.
      Patients either received botulinum toxin A (20 to 50 units) or saline injection
      at the first treatment, and the opposite treatment 4 months later. Prospective
      data including tinnitus matching test, tinnitus handicap inventory (THI),
      tinnitus rating scale (TRS), and patient questionnaires were obtained over a 4
      month period after each injection. RESULTS: Twenty-six patients completed both
      injections and follow-up and were included in data analysis. After botulinum
      toxin A, subjective tinnitus changes included 7 patients improved, 3 worsened,
      and 16 unchanged. Following placebo, 2 patients were improved, 7 worsened, and 17
      unchanged. Comparison of the treatment and placebo groups was statistically
      significant (P < 0.005) when including better, worse, and same effects. A
      significant decrease in THI scores between pretreatment and 4 month postbotulinum
      toxin A injection (P = 0.0422) was recorded. None of the other comparisons of
      pretreatment to 1 month, or pretreatment to 4 months were significantly
      different. CONCLUSIONS: This small study found improvement in THI scores and
      patient subjective results after botulinum toxin A injection compared with
      placebo, suggesting a possible benefit of botulinum toxin A in tinnitus
      management. Larger studies need to be completed to further evaluate potential
      benefits of botulinum toxin A in treatment of this difficult problem.

PMID- 15944560
TI  - Etiologic diagnosis of sensorineural hearing loss in adults.
AB  - OBJECTIVE: To determine the etiology of adult-onset sensorineural hearing loss.
      STUDY DESIGN AND SETTING: This is a prospective cohort study of 60 adult subjects
      with bilateral sensorineural hearing loss of no obvious etiology by medical
      history and physical examination. These patients were evaluated at an academic
      medical center and underwent evaluation by high-resolution computed tomography of
      the temporal bone, autoimmune panel, and DNA testing for mutations of both the
      GJB2 gene and the mitochondrial DNA (1555A>G and 7445A>G). RESULTS: An etiologic
      diagnosis was achieved in 6 patients: cochlear otosclerosis, 1 case; dilated
      vestibular aqueduct, 1 case; a mitochondrial DNA 7445A>G mutation, 3 cases; and a
      mitochondrial DNA 1555A>G mutation, 1 case. CONCLUSION: This result underscores
      the importance of a search for the etiology of a hearing deficit in adult
      patients. There are specific interventions now available for the management of
      hearing-impaired patients with cochlear otosclerosis and mitochondrial DNA
      mutations.

PMID- 15944561
TI  - Preoperative antibiotic and steroid therapy and hearing loss caused by
      semicircular canal transection in pseudomonas otitis media.
AB  - OBJECTIVE: The purpose of this experiment was to determine whether preoperative
      administration of antibiotics and corticosteroids can attenuate the severity of
      hearing loss (HL) with semicircular canal (SC) transection in a guinea pig model
      of Pseudomonas aeruginosa (PA) otitis media (OM). Study design and setting
      Prospective and controlled. METHODS: OM was induced in 64 pigmented guinea pigs
      by bilateral, transtympanic injection of PA. Two to 4 days later, 1 horizontal SC
      was randomly transected. In the 1st series, antibiotic therapy was initiated
      either immediately before or after surgery. In the 2nd series, all animals
      received preoperative antibiotics, and half received dexamethasone before
      surgery. Hearing was tested before and after surgery. RESULTS: PA was recovered
      in all ears. SC transection was associated with significant HL. HL was better in
      animals given antibiotics preoperatively (clicks, 16 versus 32 dB, P = 0.0220).
      Addition of preoperative steroids did not significantly further reduce HL (7
      versus 14 dB for clicks, P = 0.6919). CONCLUSIONS: HL caused by SC transection in
      PA OM may be attenuated with preoperative antibiotic therapy in the guinea pig.

PMID- 15944562
TI  - Intratympanic dexamethasone for profound idiopathic sudden sensorineural hearing
      loss.
AB  - OBJECTIVES: To determine hearing recovery by using intratympanic dexamethasone
      for profound, idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN
      AND SETTING: A prospective, clinical study was performed of 25 consecutive
      patients seen with profound ISSNHL. Patients received 4 intratympanic treatments
      of dexamethasone over the course of 2 weeks. Complete hearing recovery was
      defined as the final pure-tone average (PTA) within 10 dB of baseline. Partial
      recovery was defined as a final PTA with >/=50% hearing. The hearing in the
      contralateral ear was used as baseline. RESULTS: The average time to treatment
      was 28 days. Two patients had significant hearing recovery, and 1 additional
      patient had partial recovery. The 2 patients with significant hearing recovery
      were treated within 9 days of onset of hearing loss. CONCLUSIONS: By using the
      treatment protocol and definition of hearing recovery of this study,
      intratympanic dexamethasone does not result in significant hearing improvement
      for patients with profound ISSNHL. There is a possible trend for improved hearing
      results if intratympanic treatment is performed within 11 days of onset of
      hearing loss.

PMID- 15944563
TI  - Total tympanic membrane reconstruction: AlloDerm versus temporalis fascia.
AB  - BACKGROUND AND OBJECTIVE: Patients who require surgery for chronic otitis media
      with perforation and cholesteatoma frequently provide no residual tympanic
      membrane that is usable in grafting procedures. A novel technique of total
      tympanic membrane reconstruction (TTMR) is described that maximizes perforation
      closure rate in these situations while minimizing mucosalization, incomplete
      healing, and anterior blunting. The specific aim of this report is to assess the
      safety and efficacy of TTMR and to compare the results obtained with AlloDerm
      compared with temporalis fascia as a grafting material. METHODS: The records of
      50 patients operated within the years 1999 and the 2004 were reviewed. TTMR with
      intact canal wall was performed in all cases. Both clinical and audiometric data
      were analyzed. RESULTS: Overall perforation closure rate was 92%. There was no
      statistical significance in closure rate when grafting with AlloDerm versus
      temporalis fascia. A statistically significant shortened healing time was
      observed with AlloDerm grafting. CONCLUSIONS: TTMR is a highly effective and safe
      technique.

PMID- 15944564
TI  - Ion channel proteins in mouse and human vestibular tissue.
AB  - BACKGROUND AND OBJECTIVE: Electrical activity in hair cells and neurons of the
      inner ear is necessary for the transduction and modulation of stimuli that
      impinge on the cochlea and vestibular endorgans of the inner ear. The underlying
      basis of this activity is pore-forming proteins in the membrane of excitable
      cells that allow the influx and efflux of various ions, including Na + , Ca 2+ ,
      and K + , among others. These channels are critical to both electrical activity
      as well as the development of excitable cells because they may initiate long-term
      signals that are important in the maintenance and survival of these cells. We
      investigated the expression of several Shaker potassium ion channel proteins and
      an accessory beta subunit in the vestibular endorgans of mouse and human.
      METHODS: Vestibular tissue consisting of cristae ampullares was harvested from
      adult and neonatal mice as well as from human subjects undergoing vestibular
      surgery. Western blot analysis and immunoprecipitation were used to identify the
      presence or absence, in mouse, of alpha subunits Kv1.2, Kv1.4, and Kv1.5 and of
      beta subunit Kvbeta1.1 in mouse. Coimmunoprecipitation was used to identify
      interactions between alpha and beta subunits. Immunohistochemistry was used to
      localize Kv1.2 in mouse and human tissues. RESULTS: The presence of Kvalpha1.2
      and Kvbeta1.1 was confirmed in adult mouse crista ampullaris by Western blotting.
      Coimmunoprecipitation experiments showed that Kv1.2 and Kvbeta1.1 interact in
      these tissues. Immunostaining localized Kv1.2 to regions within and extraneous to
      the sensory epithelium of mouse and human cristae ampullares. In comparison,
      Kv1.4 and Kv1.5 were not found in the crista ampullaris. CONCLUSIONS: We describe
      the presence, location, and interaction of various potassium ion channel alpha
      subunits and a beta subunit. These data are initial descriptions of potassium ion
      channels in the mammalian vestibular system and begin to provide an understanding
      of the protein subunits that form ion channels of the mammalian inner ear. In
      addition, our data show that there are interactions that occur that may regulate
      the biophysical properties of these channels, thereby contributing to the
      diversity of channel function. This knowledge is critical to understanding the
      genes that encode these channels and finding cures for pathologies of hearing and
      balance. SIGNIFICANCE: We detail initial characteristics of potassium ion channel
      proteins including alpha subunits Kv1.2, Kv1.4, and Kv1.5 and beta subunit
      Kvbeta1.1 in mammalian vestibular tissue. This knowledge is critical to
      understanding the processing of vestibular stimuli and the regulation of
      endolymphatic function. Mutations of ion channels can cause neurological
      pathologies including auditory and vestibular disorders in humans.

PMID- 15944565
TI  - Laser myringotomy for otitis media with effusion in nasopharyngeal carcinoma
      patients.
AB  - OBJECTIVE: To evaluate the effectiveness of laser myringotomy in otitis media
      with effusion (OME) in patients with nasopharyngeal carcinoma (NPC). STUDY DESIGN
      AND SETTING: Laser myringotomy was performed with a CO 2 laser otoscope in 53 NPC
      patients (68 ears) and 32 non-NPC patients (37 ears). All patients had a history
      of OME. RESULTS: In the NPC group, 40% of ears developed persistent perforation,
      37% had recurrent OME, and 23% were free of disease. In the non-NPC group, only
      3% of ears developed persistent perforation, and 43% were free of disease.
      Significant differences in perforation and disease-free state were evident
      between the 2 groups. Tumor stage was found to be a significant determining
      factor for clinical outcome in NPC group. CONCLUSION: Laser myringotomy for NPC
      group carries a significantly higher risk of persistent perforation and lower
      rate of cure. This procedure may be considered for early staging NPC patients
      with serious OME symptoms.

PMID- 15944566
TI  - Localization by unilateral BAHA users.
AB  - OBJECTIVES: Patients with unilateral hearing loss report difficulty hearing
      conversation on their impaired side, localizing sound, and understanding of
      speech in background noise. The bone-anchored cochlear stimulator (BAHA)
      (Entific, Gothenburg, Sweden) has been shown to improve performance in persons
      with unilateral severe-profound sensorineural loss (USNHL). The purpose of this
      study is to evaluate the effectiveness of BAHA in sound localization for USNHL
      listeners. STUDY DESIGN: Prospective study of 12 USNHL subjects, 9 of whom
      received implants on the poorer hearing side. A control group of 10 normal
      hearing subjects were assessed for comparison. Localization with and without BAHA
      was assessed using an array of 8 speakers at head level separated by 45 degrees.
      Error analysis matrix was generated to evaluate the confusions, accuracy in
      response, and laterality judgment. RESULTS: The average accuracy of speaker
      localization was 16% in the unaided condition, with no improvement with BAHA use.
      Laterality judgment was poorer than 43% in both aided and nonaided conditions.
      CONCLUSIONS: Patients with UNSNHL had poor sound localization and laterality
      judgment abilities that did not improve with BAHA use.

PMID- 15944567
TI  - Hearing results after primary cartilage tympanoplasty with island technique.
AB  - OBJECTIVE: Because of its rigid quality, cartilage is the grafting material of
      choice in advanced pathologies, such as adhesive processes or recurrent
      perforations. However, the use of such a rigid material in tympanic membrane
      reconstruction causes controversies as to the audiologic aspect. The purpose of
      this study was to assess overall and frequency-specific hearing results after
      primary cartilage tympanoplasty with island technique in comparison to the
      hearing results after primary tympanoplasty with temporalis muscle fascia. STUDY
      DESIGN AND SETTING: This study was a retrospective review of selected cases
      between 1999 and 2002. Primary cases with intact ossicular chain, normal middle
      ear mucosa, and subtotal perforation of the tympanic membrane were included in
      the study. Fifteen patients were in the cartilage group, whereas 10 patients were
      in the fascia group. Preoperative and postoperative air-bone gaps at the
      frequencies of 0.5, 1, 2, and 4 kHz were compared. RESULTS: Both groups were
      statistically similar on the aspect of the severity of middle ear pathology and
      the preoperative hearing levels. Mean postoperative gains in air-bone gap were
      11.9 dB for the cartilage group and 11.5 dB for the fascia group. There were no
      statistically significant differences in the postoperative frequency-specific
      gains in air-bone gap between the 2 groups. CONCLUSIONS: Although cartilage is
      the ideal grafting material in problem cases, its comparable acoustic properties,
      especially in the form of cartilage island, to those of fascia will allow a more
      liberal application in less severe cases, in which functional outcome is more
      essential.

PMID- 15944568
TI  - Pediatric dermoid cysts of the head and neck.
AB  - OBJECTIVE: To review the characteristics and determine treatment outcomes of
      pediatric dermoid cysts. STUDY DESIGN AND SETTING: Retrospective review of the
      presentation, diagnosis, treatment, and outcomes of all pediatric dermoid cysts
      of the head and neck examined between 1980 and 2002 at Mayo Clinic. RESULTS:
      Forty-nine patients (59% girls) had a dermoid cyst of the head and neck. The
      median age at diagnosis was 22 months. The most common presenting sign was a
      palpable mass, noted in 100% of patients. During evaluation, approximately 25
      patients (51%) had imaging studies. The most common location of the cysts was
      periorbital (61%), followed by the neck (18%; including 1 submental cyst).
      Various surgical approaches were chosen. In 2 patients (4%), the dermoid cyst had
      an intracranial extension. Only 1 patient experienced recurrence. The median
      pathologic diameter of the cysts was 1.2 cm. CONCLUSIONS: Dermoid cysts are
      unusual neoplasms that often present in childhood, with the orbit being the area
      most commonly affected in the head and neck region. Imaging studies help rule out
      an intracranial or intraorbital extension. With complete excision, recurrence is
      unusual. Significance Our review will assist both primary care physicians and
      subspecialists in diagnosing and treating dermoid cysts.

PMID- 15944569
TI  - Deep neck infection in diabetic patients: comparison of clinical picture and
      outcomes with nondiabetic patients.
AB  - OBJECTIVE: To compare the difference in the clinical picture and outcomes between
      diabetic and nondiabetic patients with deep neck infections. STUDY DESIGN AND
      SETTING: We retrospectively reviewed the records of patients who were diagnosed
      with deep neck infections and who received treatment at the Department of
      Otolaryngology of National Taiwan University Hospital between 1997 and 2002. One
      hundred eighty-five patients were included in our study. Fifty-six patients with
      diabetes mellitus were enrolled for further analysis (diabetic group) and
      compared with the other 129 patients without diabetes mellitus (nondiabetic
      group) in demography, etiology, bacteriology, treatment, duration of hospital
      stay, complications, and outcome. RESULTS: The parapharyngeal space was the space
      most commonly involved in both the diabetic (33.9%) and nondiabetic groups
      (40.3%). Odontogenic infections and upper airway infections were the 2 leading
      causes of deep neck infection in diabetic and nondiabetic groups. Streptococcus
      viridans is the most commonly isolated organism in the nondiabetic group (43.7%).
      However, the most common organism in the diabetic group was Klebsiella pneumoniae
      (56.1%). There were 89.3% of diabetic patients, versus 71.3% of nondiabetic
      patients, with abscess formation ( P = 0.0136). Surgical drainage was performed
      more frequently in the diabetic group than in the nondiabetic group (86.0% versus
      65.2%, P = 0.0142). In comparison with the nondiabetic group, the diabetic group
      tended to have older mean age (57.2 y versus 46.2 y, P = 0.0007), longer duration
      of hospital stay (19.7 days versus 10.2 days, P < 0.0001), more frequent
      complications (33.9% versus 8.5%, P < 0.0001), and more frequent tracheostomy or
      intubation (19.6% versus 6.2%, P = 0.0123). CONCLUSIONS: Patients with diabetes
      mellitus are susceptible to deep neck infection. We should pay more attention
      when dealing with deep neck infections in patients with diabetes mellitus because
      those patients tend to have complications more frequently and a longer duration
      of hospital stay. Empirical antibiotics should cover K. pneumoniae in patients
      with deep neck infection who have diabetes mellitus.

PMID- 15944570
TI  - Comparison of quality of life outcomes in laryngeal cancer patients following
      chemoradiation vs. total laryngectomy.
AB  - OBJECTIVE: To evaluate quality of life issues in patients with laryngeal cancer
      after treatment with either chemoradiation or total laryngectomy and radiation
      therapy. METHODS: Forty-nine patients with a history of stage II-IV laryngeal
      squamous cell carcinoma treated primarily with either chemoradiation or by total
      laryngectomy with postoperative radiation completed the University of Washington
      Quality of Life instrument, version 4. Patients were identified on a volunteer
      basis in an academic university head and neck clinic setting. Each patient
      completed the above instrument, and statistical analysis was performed by
      Wilcoxon and chi 2 tests. RESULTS: Instruments were completed by all 49 patients:
      15 patients who underwent primary chemoradiation and 34 patients who underwent a
      total laryngectomy followed by radiation. Domains reported in both treatment
      groups without significant differences were appearance, activity, recreation,
      moods, taste, saliva, anxiety, and general questions. However, there were
      significant differences between the 2 groups in the domains of pain, swallowing,
      chewing, speech, and shoulder function. The laryngectomy patients reported
      greater impairment of speech (P = 0.001), and shoulder function (P = 0.018),
      whereas the chemoradiation patients suffered from greater pain, difficulty
      swallowing (P = 0.061), and problems chewing (P = 0.027). CONCLUSIONS: Most
      patients with laryngeal cancer, whether treated primarily with chemoradiation or
      total laryngectomy, reported excellent functional outcomes and health-related
      quality of life. Pain, swallowing, chewing, saliva, and shoulder function were
      recorded as significant factors affecting their daily quality of life.

PMID- 15944571
TI  - Extramedullary hematopoiesis of the paranasal sinuses in sickle cell disease.

PMID- 15944572
TI  - Cervicofacial actinomycosis.

PMID- 15944573
TI  - Bilateral squamous cell carcinoma of the external auditory canal.

PMID- 15944574
TI  - Schwannoma of the nasal septum removed with endoscopic surgery.
AB  - A 50-year-old woman presented with a 30-year history of nasal obstruction. She
      had been treated for paranasal sinusitis at other hospitals and she was referred
      to our hospital for further examination. Flexible endoscopy revealed a mass in
      the posterior aspect of the right nasal cavity to the posterior aspect of the
      left nasal cavity around the posterior edge of the nasal septum.

PMID- 15944575
TI  - Bacterial meningitis complicating suppurative otitis media and sinusitis.

PMID- 15944576
TI  - Tuberculosis of the larynx associated with orofacial granulomatosis in childhood.

PMID- 15944585
TI  - Endovascular repair of abdominal aortic aneurysm reduces intraoperative cortisol
      and perioperative morbidity.
AB  - BACKGROUND: The release of catabolic stress hormones because of surgical trauma
      leads to a breakdown of fats, proteins, and carbohydrate stores and interference
      with immune function. This can delay wound healing and may increase the risk of
      systemic inflammatory response syndrome (SIRS)/sepsis and postoperative
      complications. Minimally invasive surgery can attenuate this response. Our
      purpose was (1) to compare neuroendocrine responses in patients undergoing open
      abdominal aneurysm repair with those in patients undergoing endovascular aneurysm
      repair (EVAR), (2) to compare the incidence of SIRS/sepsis and all complications
      in these two groups, and (3) to look at the relationship between procedure type,
      neuroendocrine response, and incidence of SIRS/sepsis and complications. METHODS:
      Forty-six patients who underwent open repair and 19 who underwent EVAR were
      studied. A baseline (T1) 24-hour urine save was undertaken in the week before
      admission, and a second 24-hour save (T2) commenced at anesthetic induction to
      measure cortisol and catecholamines. The incidences of SIRS/sepsis and
      complications were recorded. RESULTS: Significant ( P </= .001) increases in
      cortisol and adrenaline from T1 to T2 occurred in all patients. Controlling for
      the type of anesthetic, the administration of exogenous inotropes, and beta
      adrenoreceptor antagonists (beta-blockers), there was a significant difference in
      cortisol (T2) associated with the type of procedure. Responses were greater in
      open patients in comparison to EVAR patients (F 3,61 = 5.0; P = .03). The
      incidence of SIRS (50% vs 32%), sepsis (26% vs 5%), and all complications (76% vs
      32%) was significantly ( P </= .02) higher in open than EVAR patients,
      respectively. Cortisol and adrenaline measured for 24 hours, commencing at the
      time of induction, tended to be higher in patients with SIRS/sepsis and all
      complications, but this did not reach significance. CONCLUSIONS: An attenuated
      glucocorticoid surge characterizes the reduced stress response experienced by
      patients undergoing EVAR compared with open abdominal aortic aneurysm repair. A
      reduction in the occurrence of SIRS is a feature of a more favorable
      postoperative course after an endovascular approach.

PMID- 15944586
TI  - The impact of aortic endografts on renal function.
AB  - OBJECTIVE: To determine the impact on late postoperative renal function of
      suprarenal and infrarenal fixation of endografts used to treat infrarenal
      abdominal aortic aneurysm (AAA). METHODS: Retrospective analysis of 277 patients
      treated from 2000 to 2003 with three different endografts at two clinical
      centers. Five patients on dialysis for preoperative chronic renal failure were
      excluded. Group IF of 135 patients treated with an infrarenal device (Medtronic
      AneuRx) was compared with group SF of 137 patients treated with a suprarenal
      device (106 Cook Zenith and 31 Medtronic Talent). Renal function was evaluated by
      calculating preoperative and latest postoperative creatinine clearance (CrCl)
      using the Cockcroft formula. Patients who developed a >20% decrease in CrCl were
      considered to have significantly impaired renal function. RESULTS: There were no
      significant differences in patient age, sex, aneurysm size, preoperative risk
      factors, dose of intra- and postoperative contrast, or baseline CrCl (IF: 69.3
      mL/min, SF: 71.7 mL/min, P = .4). Follow-up time of 12.2 months was the same in
      both groups. CrCl decreased significantly during the follow-up period in both
      groups (IF: 69.3 mL/min to 61.7 mL/min, P < .01; SF: 71.7 mL/min to 64.9 mL/min,
      P < .03). Postoperative CrCl (IF: 61.7 mL/min, SF: 64.9 mL/min, P = .3), and the
      rate of CrCl decrease during the follow-up period (IF: -10.9%, SF: -9.5%, P = .2)
      was not different between the two groups. The number of patients with a >20%
      decrease in CrCl was not different between the two groups (IF: n = 35 [25.9%],
      SF: n = 41 [29.9%], P = .46). However, the magnitude of decrease in CrCl in
      patients with renal impairment was greater in patients treated with suprarenal
      fixation endografts (SF: -39%) compared with those treated with infrarenal
      endografts (IF: -31%, P = .005). This greater degree of renal impairment was not
      due to identifiable differences in preoperative risk factors, age, or baseline
      CrCl. No patients in these series required dialysis. CONCLUSIONS: Regardless the
      type of endograft used, there is a 10% decrease in CrCl in the first year after
      endovascular aneurysm repair. Suprarenal fixation does not seem to increase the
      likelihood of postoperative renal impairment. Decline in renal function over time
      after endovascular aortic repair is probably due to multiple factors, and
      measures known to be effective in protecting kidneys should be considered for
      these patients. Long-term follow-up with measurement of CrCl, along with renal
      imaging and regular blood pressure measurements, should be performed to detect
      possible late renal dysfunction. Prospective studies comparing suprarenal versus
      infrarenal fixation are needed to confirm those results.

PMID- 15944587
TI  - Open repair of chronic post-traumatic aneurysms of the aortic isthmus: the value
      of direct aortoaortic anastomosis.
AB  - PURPOSE: This report presents our experience with open repair of post-traumatic
      aneurysms of the aortic isthmus using recent surgical techniques, including
      distal aortic perfusion and the preferential use of direct aortoaortic
      anastomosis without interposition of prosthetic material. METHODS: From 1990 to
      2004, the senior author (EK) patients (21 men; mean age, 40.3 years) who
      presented with post-traumatic aneurysms of the aortic isthmus were treated
      operatively, either with (20 patients) or without (3 patients) distal aortic
      perfusion, or endovascularly with a stent graft (3 patients). In 15 (75 %) of the
      20 patients treated with distal aortic perfusion, the technique consisted of
      resection followed by direct aortoaortic anastomosis. Eight patients, including
      the three patients treated with simple clamping, had prosthetic replacement.
      RESULTS: No postoperative deaths or permanent spinal cord complications occurred.
      One patient required reoperation to control hemorrhage. Aortography or computed
      tomography angiography was performed on 12 of the 15 patients treated by direct
      aortoaortic anastomosis, with a mean follow-up of 58.7 +/- 8.9 months. No
      morphologic abnormality was found. CONCLUSION: This study shows that low-risk
      patients with a chronic post-traumatic aneurysm of the aortic isthmus can be
      successfully treated with excellent long-term results by resection and direct
      aortoaortic anastomosis without prosthetic interposition. In our opinion,
      endovascular repair should only be used in patients who present with absolute
      contraindications for open surgical repair.

PMID- 15944589
TI  - The value of duplex surveillance after open and endovascular popliteal aneurysm
      repair.
AB  - OBJECTIVE: The objective of this study was to determine the clinical value of
      vascular laboratory surveillance after open or endovascular repair of popliteal
      aneurysm by analysis of the frequency and nature of secondary interventions
      performed. METHODS: Over an 8-year period, 55 popliteal artery aneurysms were
      repaired in 46 men (mean age, 72 years) by aneurysm ligation and bypass grafting
      (vein, 37; prosthetic, 7), endoaneurysmorrhaphy and interposition grafting
      (prosthetic, 3; vein, 1), or endograft exclusion (n = 7). Indications for
      intervention included aneurysm thrombosis with critical limb ischemia (n = 8),
      symptomatic (n = 10) or asymptomatic (n = 37), >1.75 cm popliteal aneurysm with
      mural thrombus. Catheter-directed thrombolysis was used in three limbs to restore
      aneurysm and tibial artery patency before open repair. Duplex ultrasound
      surveillance was performed after repair to identify residual and acquired
      lesions. Life-table analysis was used to estimate repair site intervention-free
      (primary) and assisted-primary patency. RESULTS: During a mean 20-month follow-up
      interval, 20 secondary procedures were performed in 18 (31%) limbs to repair
      duplex-detected graft stenosis (n = 10), repair site thrombosis (n = 5), vein
      graft aneurysm (n = 3), graft entrapment (n = 1), or type 1 endoleak (n = 1).
      Primary patency was 76% and 68% at 1 and 3 years, and was uninfluenced by tibial
      artery runoff status or type of bypass conduit. Open (n = 12) or endovascular (n
      = 8) secondary procedures were performed on 15 (12 vein, 3 prosthetic) bypass
      grafts, 2 endografts, and 1 interposition graft. Mean time to repair graft
      stenosis (11 months) was shorter than to repair of vein graft aneurysm (37
      months). Assisted-primary patency was 93% and 88% at 1 and 3 years; redo bypass
      grafting was required and successful in five limbs. Limb salvage was 100%.
      CONCLUSIONS: One third of popliteal artery aneurysms repaired by open or
      endovascular procedures required a secondary intervention within 2 years of
      repair. Repair-site surveillance using duplex ultrasound was able to identify
      lesions that threaten patency, which resulted in excellent assisted patency and
      limb preservation rates when corrected.

PMID- 15944590
TI  - Safety and efficacy of reoperative carotid endarterectomy: a 14-year experience.
AB  - BACKGROUND: Reoperative carotid endarterectomy (CEA) is an accepted treatment for
      recurrent carotid stenosis. With reports of a higher operative morbidity than
      primary CEA and the advent of carotid stenting, catheter-based therapy has been
      advocated as the primary treatment for this reportedly "high-risk" subgroup. This
      study reviews a contemporary experience with reoperative CEA to validate the high
      risk categorization of these patients. METHODS: From 1989 to 2002, 153
      consecutive, isolated (excluding CEA/coronary artery bypass graft and carotid
      bypass operations) reoperative CEA procedures were reviewed. Clinical and
      demographic variables potentially associated with the end points of perioperative
      morbidity, long-term durability, and late survival were assessed with
      multivariate analysis. RESULTS: There were 153 reoperative CEA procedures in 145
      patients (56% men, 36% symptomatic) with an average age of 69 +/- 1.3 years. The
      average time from primary CEA (68% primary closure, 23% prosthetic, 9% vein
      patch) to reoperative CEA was 6.1 +/- 0.4 years (range, 0.3 to 20.4 years). At
      reoperation, patch reconstruction was undertaken in 93% of cases. The
      perioperative stroke rate was 1.9%, with no deaths or cardiac complications.
      Other complications included cranial nerve injury (1.3%) and hematoma (3.2%).
      Average follow-up after reoperative CEA was 4.4 +/- 0.3 years (range, 0.1 to 12.7
      years), with an overall total stroke-free rate of 96% and a restenosis rate
      (>50%) by carotid duplex of 9.2%. Among variables assessed for association with
      restenosis after reoperative CEA, only younger age was found to be significant
      (66 +/- 2.5 years vs 70 +/- 0.7 years, P < .05). The all-cause long-term
      mortality rate was 29%. Multivariate analysis of long-term survival identified
      diabetes mellitus as having a negative impact (hazard ratio, 3.4 +/- 0.3, P <
      .05) and lipid-lowering agents as having a protective effect (hazard ratio, 0.42
      +/- 0.4, P < .05) on survival. CONCLUSION: Reoperative CEA is a safe and durable
      procedure, comparable to reported standards for primary CEA, for long-term
      protection from stroke. These data do not support the contention that patients
      who require reoperative CEA constitute a "high-risk" subgroup in whom reoperative
      therapy should be avoided.

PMID- 15944592
TI  - The capture of visible debris by distal cerebral protection filters during
      carotid artery stenting: Is it predictable?
AB  - OBJECTIVES: Neurologic complications during carotid artery stenting (CAS) are
      most clearly associated with embolization of visible debris. Distal filter
      devices may provide cerebral protection by capturing clinically significant
      debris. However, they increase procedural time and expense and have their own set
      of complications. The current study was undertaken to identify the clinical
      factors predictive for the presence or absence of visible debris captured by
      distal filter devices during CAS. METHODS: Patients undergoing CAS with use of a
      distal filter device (n = 279) were prospectively entered into an investigational
      carotid registry. Recorded variables were classified as patient-, lesion-, or
      procedure-related. The filter was assessed for visible debris in each case. The
      odds ratio (OR) and 95% confidence interval (CI) were determined for each
      variable to predict visible debris. The ability of each variable to predict the
      absence of visible debris was assessed by calculating the individual negative
      predictive value (NPV). RESULTS: Visible debris was present in 169 filters
      (60.3%). There was an increased risk of visible debris found with several
      variables (OR, 95% CI): hypertension (2.9, 1.7 to 5.2), hypercholesterolemia
      (2.3, 1.4 to 3.9), stent diameter >9 mm (16.6, 9.0 to 30.0), and any neurologic
      event (4.2, 1.5 to 9.9). The NPV failed to exceed 0.80 (80%) for any variable.
      The NPV of the variables with a significantly elevated OR was as follows:
      hypertension (0.60), hypercholesterolemia (0.52), stent diameter >9 mm (0.75),
      and any neurologic event (0.38). CONCLUSIONS: Several clinical variables are
      associated with the presence of visible debris captured by distal filter devices.
      The current study failed to identify any variables capable of consistently
      predicting the absence of visible debris. These findings support the routine
      rather than the selective use of cerebral protection during CAS.

PMID- 15944593
TI  - Carotid angioplasty and stent-induced bradycardia and hypotension: Impact of
      prophylactic atropine administration and prior carotid endarterectomy.
AB  - OBJECTIVE: We compared the physiologic effect of selective atropine
      administration for bradycardia with routine prophylactic administration, before
      balloon inflation, during carotid angioplasty and stenting (CAS). We also
      compared the incidence of procedural bradycardia and hypotension for CAS in
      patients with primary stenosis vs those with prior ipsilateral carotid
      endarterectomy (CEA). METHODS: A total of 86 patients were treated with CAS at 3
      institutions. Complete periprocedural information was available for 75 of these
      patients. The median degree of stenosis was 90% (range, 60%-99%). Indications for
      CAS were severe comorbidities (n = 49), prior CEA (n = 21), and prior neck
      radiation (n = 5). Twenty patients with primary lesions were treated selectively
      with atropine only if symptomatic bradycardia occurred (nonprophylactic group).
      Thirty-four patients with primary lesions received routine prophylactic atropine
      administration before balloon inflation or stent deployment (prophylactic group).
      The 21 patients with prior CEA received selective atropine treatment only if
      symptomatic bradycardia occurred (prior CEA group) and were analyzed separately.
      Mean age and cardiac comorbidities did not vary significantly either between the
      prophylactic and nonprophylactic atropine groups or between the primary and prior
      CEA patient groups. Outcome measures included bradycardia (decrease in heart rate
      >50% or absolute heart rate <40 bpm), hypotension (systolic blood pressure <90 mm
      Hg or mean blood pressure <50 mm Hg), requirement for vasopressors, and cardiac
      morbidity (myocardial infarction or congestive heart failure). RESULTS: The
      overall incidence of hypotension and bradycardia in patients treated with CAS was
      25 (33%) of 75. A decreased incidence of intraoperative bradycardia (9% vs 50%; P
      < .001) and perioperative cardiac morbidity (0% vs 15%; P < .05) was observed in
      patients with primary stenosis who received prophylactic atropine as compared
      with patients who did not receive prophylactic atropine. CAS after prior CEA was
      associated with a significantly lower incidence of perioperative bradycardia (10%
      vs 33%; P < .05), hypotension (5% vs 32%; P < .05), and vasopressor requirement
      (5% vs 30%; P < .05), with a trend toward a lower incidence of cardiac morbidity
      (0% vs 6%; not significant) as compared with patients treated with CAS for
      primary carotid lesions. There were no significant predictive demographic factors
      for bradycardia and hypotension after CAS. CONCLUSIONS: The administration of
      prophylactic atropine before balloon inflation during CAS decreases the incidence
      of intraoperative bradycardia and cardiac morbidity in primary CAS patients.
      Periprocedural bradycardia, hypotension, and the need for vasopressors occur more
      frequently with primary CAS than with redo CAS procedures. On the basis of our
      data, we recommend that prophylactic atropine administration be considered in
      patients with primary carotid lesions undergoing CAS.

PMID- 15944595
TI  - Sensitivity and specificity of color duplex ultrasound measurement in the
      estimation of internal carotid artery stenosis: a systematic review and meta
      analysis.
AB  - BACKGROUND: Duplex ultrasound is widely used for the diagnosis of internal
      carotid artery stenosis. Standard duplex ultrasound criteria for the grading of
      internal carotid artery stenosis do not exist; thus, we conducted a systematic
      review and meta-analysis of the relation between the degree of internal carotid
      artery stenosis by duplex ultrasound criteria and degree of stenosis by
      angiography. METHODS: Data were gathered from Medline from January 1966 to
      January 2003, the Cochrane Central Register of Controlled Trials and Database of
      Systematic Reviews, Database of Abstracts of Reviews of Effects, ACP Journal
      Club, UpToDate, reference lists, and authors' files. Inclusion criteria were the
      comparison of color duplex ultrasound results with angiography by the North
      American Symptomatic Carotid Endarterectomy Trial method; peer-reviewed
      publications, and >/=10 adults. RESULTS: Variables extracted included internal
      carotid artery peak systolic velocity, internal carotid artery end diastolic
      velocity, internal carotid artery/common carotid artery peak systolic velocity
      ratio, sensitivity and specificity of duplex ultrasound scanning for internal
      carotid artery stenosis by angiography. The Standards for Reporting of Diagnostic
      Accuracy (STARD) criteria were used to assess study quality. Sensitivity and
      specificity for duplex ultrasound criteria were combined as weighted means by
      using a random effects model. The threshold of peak systolic velocity >/=130 cm/s
      is associated with sensitivity of 98% (95% confidence intervals [CI], 97% to
      100%) and specificity of 88% (95% CI, 76% to 100%) in the identification of
      angiographic stenosis of >/=50%. For the diagnosis of angiographic stenosis of
      >/=70%, a peak systolic velocity >/=200 cm/s has a sensitivity of 90% (95% CI,
      84% to 94%) and a specificity of 94% (95% CI, 88% to 97%). For each duplex
      ultrasound threshold, measurement properties vary widely between laboratories,
      and the magnitude of the variation is clinically important. The heterogeneity
      observed in the measurement properties of duplex ultrasound may be caused by
      differences in patients, study design, equipment, techniques or training.
      CONCLUSIONS: Clinicians need to be aware of the limitations of duplex ultrasound
      scanning when making management decisions.

PMID- 15944596
TI  - Renovascular disease in children and adolescents.
AB  - PURPOSE: This retrospective review describes the surgical management of
      renovascular disease in 25 consecutive children and adolescents with severe
      hypertension. METHODS: Patients </=21 years of age (mean age, 11.6 +/- 5.4 years;
      12 females, 13 males) underwent repair of 34 renal arteries (RAs), and their
      management forms the basis of this report. Early and late blood pressure
      responses were adjusted for gender, age, and height. RA repair was evaluated by
      angiography, renal duplex sonography (RDS) scanning, or both. Primary patency and
      survival were estimated by product-limit methods. RESULTS: Thirty-four RAs among
      32 kidneys were repaired. Bilateral renal RA disease to a solitary kidney was
      present in nine patients. RA lesions included dysplasia (44%), RA hypoplasia
      (20%), midaortic syndrome (12%), RA aneurysm (12%), dissection (8%), and
      arteritis (4%). All patients had severe hypertension (>95 th percentile systolic
      or diastolic pressure adjusted for gender, age, and height). RA repair comprised
      25 bypasses (73%) consisting of 28% saphenous vein, 60% hypogastric artery, and
      12% polytetrafluoroethylene; 2 patch angioplasties (6%), and 7 reimplantations
      (21%). Branch RA exposure was required in 28 kidneys (88%), and branch
      reconstruction was required in 61%. Warm in situ repair was used in 53%, in situ
      cold perfusion in 24%, and ex vivo cold perfusion in 23%. Of six bilateral RA
      repairs, one was staged and two patients are awaiting a staged repair. Combined
      aortic reconstruction was required in three patients. No unplanned nephrectomy
      was performed. There were no perioperative deaths. Hypertension was cured in 36%,
      improved in 56%, and failed in 8% at mean follow-up of 46.4 +/- 7.8 months. The
      mean calculated glomerular filtration rate increased from 82.0 mL/min/1.73 m 2
      preoperatively to 98.2 mL/min/1.73 m 2 postoperatively. The postoperative patency
      of 30 RA reconstructions was evaluated by angiography, RDS scanning, or both. At
      mean follow-up of 32.8 months (median, 21.2 months), primary RA patency was 91%.
      No failures were observed after 2 months follow-up. Estimated survival was 100%
      at 60 months, with one death 9 years after surgery. CONCLUSIONS: Renovascular
      hypertension in children and adolescents was caused by a heterogeneous group of
      lesions. All patients had RA repair, with arterial autografts in most of the RA
      bypasses. Cold perfusion preservation was used in half of the complex branch RA
      repairs. These strategies provided 91% primary patency at mean follow-up of 32.8
      months, with beneficial blood pressure response in 92%. Surgical repair of
      clinically significant renovascular disease in children and adolescents is
      supported by these results.

PMID- 15944597
TI  - Open surgical repair of children less than 13 years old with lower extremity
      vascular injury.
AB  - PURPOSE: We sought to review the diagnosis and treatment of children with lower
      extremity vascular injury. METHODS: We performed a query of our vascular surgery
      database from 1996 through 2002 to determine those with lower extremity vascular
      injuries requiring surgery who were also less than 13 years of age. Patient
      demographics, presentation, cause, surgical specifics, and outcome were sought.
      RESULTS: Six children (2 girls and 4 boys) with an average age of 6.8 years
      (range, 2-9 years) were found. The causes were 3 blunt injuries, 2 iatrogenic
      injuries, and 1 penetrating injury. Associated injuries were common. There were 3
      femoral and 3 popliteal artery injuries. Two were pseudoaneurysms (common femoral
      and popliteal artery), and 4 were acute occlusions, of which 3 experienced a
      delay in diagnosis. There was one primary below-knee amputation. Four reverse
      vein bypasses were performed, and one vein patch repair of a pseudoaneurysm was
      performed. Generally, 7 to 9 O interrupted Prolene (Ethicon, Inc, Somerville, NJ)
      repairs were performed. A delay in diagnosis (2 blunt injuries) resulted in 2
      major amputations and 1 insensate foot. Four reconstructions are functioning with
      viable limbs (follow-up, 5-49 months). An associated brain injury resulted in the
      only death. CONCLUSIONS: Vascular blunt injury is especially insidious in
      children. However, an aggressive approach of vascular repair, even extensive
      bypasses with reverse vein, will allow limb salvage in the absence of a
      diagnostic delay.

PMID- 15944598
TI  - Limb-salvage angioplasty in vascular surgery practice.
AB  - OBJECTIVE: To assess outcomes of percutaneous infrainguinal arterial angioplasty
      for treatment of chronic limb-threatening ischemia (CLI) in poor surgical
      candidates. METHODS: A retrospective clinical analysis of 67 consecutively
      treated patients (76 limbs) with CLI over a 33-month period was performed.
      Patients were considered poor surgical candidates because of absent distal target
      vessels (31 limbs), severe comorbid conditions (36 limbs), or lack of an
      autologous vein for distal bypass (9 limbs). Limb salvage was defined as
      preservation of a functional foot without the need for a prosthesis. Technical
      success was defined as the ability to percutaneously recanalize the arterial
      segment with less than 30% residual stenosis. Clinical success was healing of
      ulcers or minor amputation sites, resolving rest pain, or avoiding a major
      amputation. Successful technical and clinical outcomes were correlated with
      patient demographics, clinical presentation, and TransAtlantic Inter-Society
      Consensus arterial lesion characteristics by using the Fisher exact test.
      RESULTS: Seventy-six limbs were treated for rest pain (n = 12), gangrene (n =
      22), or nonhealing ulcers (n = 42). There were 40 men and 27 women. The mean age
      was 70 years (range, 36-94 years). Lesions were located in tibial (n = 55),
      popliteal (n = 6), and superficial femoral (n = 15) arteries. Arterial
      recanalization and limb salvage was achieved in 64 (83.5%) limbs. Technical
      failure (n = 12) correlated with TransAtlantic Inter-Society Consensus D lesions
      ( P = .009) and the presence of occlusion ( P = .027). Clinical failure (major
      amputation, n = 12) correlated with the presence of gangrene ( P = .032) or the
      combination of diabetes, arterial occlusion, and gangrene ( P = .018). The single
      variables of age, sex, diabetes, and renal failure did not adversely affect
      outcomes. There was one mortality (myocardial infarction), and there were two
      major morbidities (femoral artery pseudoaneurysm and sepsis). CONCLUSIONS:
      Peripheral arterial angioplasty should be considered as an alternative to primary
      amputation in selected patients with CLI who are poor candidates for traditional
      surgical bypass.

PMID- 15944599
TI  - Near-infrared spectroscopy and transcutaneous oxygen pressure during exercise to
      detect arterial ischemia at the buttock level: comparison with arteriography.
AB  - BACKGROUND: Noninvasive tests are required to detect (in both male and female
      subjects and side by side) arteries toward the hypogastric circulation that are
      likely to present significant lesions as a cause of buttock claudication.
      METHODS: We compared the accuracy of near-infrared spectroscopy (NIRS) and
      transcutaneous oxygen pressure (TCP o 2 ) on both buttocks during walking tests
      to detect lesions on the arteries toward the hypogastric circulation. NIRS was
      considered abnormal if recovery time to pre-exercise values was greater than 240
      seconds for tissue oxygen saturation (absent data being coded 0), and TCP o 2 was
      coded abnormal if the minimal value of buttock changes minus chest changes was
      lower than -15 mm Hg. The study was conducted in a university hospital; there
      were 30 ambulatory patients with stage 2 claudication of the Fontaine
      classification. RESULTS: Angiography showed 36 abnormal (stenosis > 75%) and 24
      normal arterial axes toward the buttocks circulation. NIRS and TCP o 2 provided
      respectively 55% (range, 41.6% to 67.9%) and 82% (range, 69.6% to 90.5%) accuracy
      (95% confidence interval) to predict the presence of arteriographically proven
      lesions; P < .05. CONCLUSIONS: Using available cut-off points proposed in the
      literature, NIRS showed a lower diagnostic accuracy than TCP o 2 for the
      prediction of lesions on the arterial tree to the hypogastric circulation. NIRS
      is a recent technique as compared with TCP o 2 , and its diagnostic accuracy
      might improve in the future. Currently, one should carefully weigh the advantages
      and limits of NIRS and TCP o 2 when a choice is to be made between them to
      monitor exercise-induced changes resulting from lower limb arterial disease at
      the proximal level.

PMID- 15944600
TI  - Frequency of critical stenosis in primary arteriovenous fistulae before
      hemodialysis access: should duplex ultrasound surveillance be the standard of
      care?
AB  - OBJECTIVE: Increasing use of primary arteriovenous fistulae (pAVFs) is a desired
      goal in hemodialysis patients (National Kidney Foundation /Dialysis Outcome
      Quality Initiative guidelines). However, in many instances, pAVFs fail to
      adequately mature due to ill-defined mechanisms. We therefore investigated pAVFs
      with color duplex ultrasound (CDU) surveillance 4 to 12 weeks postoperatively to
      identify hemodynamically significant abnormalities that may contribute to pAVF
      failure. METHODS: From March 2001 to October 2003, 54 upper extremity pAVFs were
      subjected to CDU assessment before access. A peak systolic velocity ratio (SVR)
      of >/=2:1 was used to detect >/=50% stenosis involving arterial inflow and venous
      outflow, whereas an SVR of >/=3:1 was used to detect >/=50% anastomotic stenosis.
      CDU findings were compared with preoperative vein mapping and postoperative
      fistulography when available. RESULTS: Of 54 pAVFs, there were 23
      brachiocephalic, 14 radiocephalic, and 17 basilic vein transpositions. By CDU
      surveillance, 11 (20%) were occluded and 14 (26%) were negative. Twenty-nine
      (54%) pAVFs had 38 hemodynamically significant CDU abnormalities. These included
      16 (42%) venous outflow, 13 (34%) anastomotic, and 2 (5%) inflow stenoses. In
      seven (18%), branch steal with reduced flow was found. In 35 of 54 (65%) pAVFs,
      preoperative vein mapping was available and demonstrated adequate vein size (>/=3
      mm) and outflow in 86% of cases. Twenty-one fistulograms (38%) were available for
      verifying the CDU abnormalities. In each fistulogram, the arterial inflow,
      anastomosis, and venous outflow were compared with the CDU findings (63
      segments). The sensitivity, specificity, and accuracy of CDU in detecting pAVF
      stenoses >/=50% were 93%, 94%, was 97%, respectively. CONCLUSIONS: Before
      initiation of hemodialysis, an unexpectedly high prevalence of critical stenoses
      was found in patent pAVFs using CDU surveillance. These de novo stenoses appear
      to develop rapidly after arterialization of the upper extremity superficial veins
      and can be reliably detected by CDU surveillance. Turbulent flow conditions in
      pAVFs may play a role in inducing progressive vein wall and valve leaflet intimal
      thickening, although stenoses may be due to venous abnormalities that predate AVF
      placement. Routine CDU surveillance of pAVFs should be considered to identify and
      correct flow-limiting stenoses that may compromise pAVF long-term patency and
      use.

PMID- 15944601
TI  - Arterioarterial prosthetic loop: a new approach for hemodialysis access.
AB  - OBJECTIVES: In this report we present a novel procedure that uses an
      arterioarterial prosthetic loop (AAPL) with the proximal axillary or the femoral
      artery as a vascular access for hemodialysis in patients who have inadequate
      vascular conditions for creating an arteriovenous fistula or graft. METHODS:
      Between April 1996 and September 2004, 34 patients received 36 AAPLs as vascular
      access, either as an axillary chest loop (n = 31) or as a femoral loop (n = 5).
      In this procedure the artery is ligated between the anastomoses to direct flow
      through the AAPL. Data from all patients undergoing the procedure were
      prospectively collected. RESULTS: The indication for an AAPL was the
      unsuitability of large deep veins in 64%, steal syndrome in 11%, the combination
      of only a suitable femoral vein and severe peripheral arterial disease in 22%,
      and congestive heart failure in 3%. All AAPLs were cannulated 18 +/- 4 days
      postoperatively. Mean follow-up was 31 months (range, 1 to 83). Primary patency
      was 73% and secondary patency was 96% at 1 year; these rates at 3 years were 54%
      and 87%, respectively. The rate of all interventions for the maintenance of AAPL
      function was 0.47 procedures per patient year. Four grafts were abandoned. More
      than 11,000 hemodialyses with proven efficiency were performed. CONCLUSIONS: The
      AAPL is an unusual but useful and easy-to-perform alternative procedure to create
      vascular access for hemodialysis. It can provide survival for strictly selected
      patients in whom conventional vascular access is not possible. The axillary chest
      AAPL is preferred.

PMID- 15944602
TI  - Hemodynamic changes associated with bypass stenosis regression.
AB  - OBJECTIVE: Ultrasound scanning is used to detect velocity increases indicative of
      a bypass stenosis. Subsequent examinations have shown regression of some stenotic
      lesions. This study examined hemodynamic changes that coincided with stenosis
      regression. METHODS: Duplex ultrasound scans were used to record the peak
      systolic velocity (PSV) and volume flow from proximal and distal segments of
      infrainguinal bypasses. Valve remnants or other image defects were also noted.
      The PSV ratio (Vr) was calculated as the PSV at a stenosis divided by the PSV
      proximal to the lesion. A stenosis was defined as Vr >/=2.0. RESULTS: An initial
      ultrasound scan performed 31 +/- 6 days after surgery revealed a stenosis in 68
      of 565 bypasses. In six bypasses, the increased PSV (272 +/- 61 cm/s) and Vr (3.4
      +/- 1.3) were sustained during the follow-up period of 8 +/- 3 months. In 27
      bypasses with a PSV of 335 +/- 63 cm/s and a Vr of 4.0 +/- 1.6, the stenosis was
      repaired. In 35 bypasses with a PSV of 261 +/- 82 cm/s and Vr of 3.2 +/- 1.2,
      stenosis regression occurred with no increases in PSV observed on later scans. In
      this group, proximal bypass flow decreased during the follow-up interval from 247
      +/- 130 mL/min to 151 +/- 135 mL/min and distal flow from 180 +/- 102 mL/min to
      103 +/- 54 mL/min ( P < .05, paired t test). Ultrasound image abnormalities were
      noted in 4 bypasses (67%) with persistent stenoses, 14 with repaired stenoses
      (52%), and 10 with resolved stenoses (29%). CONCLUSION: These data indicate early
      postoperative hyperemia is present in bypasses, demonstrating focal velocity
      increases. Such velocity increases may be the result of the bypass conduit acting
      as a flow-limiting lesion until the hyperemia subsides. As the blood flow
      decreases so does the PSV, giving the appearance of stenosis regression.

PMID- 15944603
TI  - The immediate effects of endovenous diode 808-nm laser in the greater saphenous
      vein: morphologic study and clinical implications.
AB  - BACKGROUND: We conducted this study to evaluate the immediate venous morphologic
      alterations produced in the great saphenous veins by the endovenous diode 808-nm
      laser used for the treatment of superficial venous insufficiency and varicose
      veins of the lower limbs and to clarify the clinical implications of the
      histologic findings. METHODS: Chosen for the study were 24 limbs of 16 patients
      with CEAP classification 3 to 6, ultrasound-documented greater saphenous
      insufficiency, and venous diameters between 3.9 mm and 17 mm (mean, 8.04 mm)
      without phlebitis, saphenous aneurysms, congenital malformations, or deep venous
      insufficiency. All limbs underwent surgical saphenofemoral disconnection, and the
      greater saphenous vein was treated with an endovenous diode 808-nm laser by
      continuous emission at 8 to 12 W and variable retraction speed (</>1 mm/s).
      Spinal or local, but not tumescent, anesthesia was used. Twenty-nine specimens (3
      to 5 cm long) of 24 proximal greater saphenous and five anterior accessory
      saphenous veins were excised and studied by light microscopy for diameter and
      thickness of the venous wall, extent of injury into the intima, media, and
      adventitia, as well as penetration of thermal damage. RESULTS: The histologic
      evaluation showed thermal injury to the intima in all specimens and full
      thickness intimal injury in 22 specimens (75%); the average penetration of
      thermal injury in 29 specimens was 194.40 microm (range, 10 to 900 microm; 14.61%
      of the mean wall thickness); complete intimal circumference injury occurred in 8
      specimen veins <10 mm in diameter (27.5%), full thickness damage in 6 (20.7%),
      and perforation in 2 (6.9%). CONCLUSIONS: Saphenous ablation using 808-nm laser
      by variable retraction speed, combined with saphenofemoral interruption, leads to
      sufficient vein wall injury to assure venous occlusion. Full thickness thermal
      injury or perforation is infrequent. Optimal results can be obtained in veins <10
      mm in diameter.

PMID- 15944605
TI  - Atheroemboli during renal artery angioplasty: an ex vivo study.
AB  - OBJECTIVE: We hypothesized that atheroemboli released during renal angioplasty
      could be responsible for the modest functional result of renal angioplasty even
      after anatomic reduction of renal artery stenosis. To test this hypothesis, we
      enumerated and sized fragments released during ex vivo angioplasty and stenting
      of human renal artery atherosclerotic specimens removed during aortorenal
      endarterectomy. METHODS: Thirty-three intact aortorenal atheroma specimens (16
      pairs with adjacent aortic atheroma and one specimen with a single renal artery
      orifice) were removed from 17 patients with renal artery occlusive disease who
      underwent renal artery endarterectomy. specimens. Endarterectomy specimens were
      removed with a ring of aortic plaque and "fitted" with a polytetrafluoroethylene
      "adventitia". Ex vivo angioplasty was technically successful in 31 of the 33
      specimens and was performed by using a 0.018-inch guidewire and 3.0-mm and 5.0-mm
      angioplasty balloons inflated for 30 seconds at 15 atmospheres pressure. Stenting
      was performed with either a 5-mm or 6-mm self-expanding Wallstent. Each artery
      was flushed with 20 mL of saline after guidewire placement, each angioplasty, and
      stent placement. The effluent was collected for analysis for counting with either
      a microscope (size >100 microm) or a Coulter counter (size <100 microm). The
      number and size of embolic fragments in the effluent collected after each
      manipulation was recorded. RESULTS: Each manipulation of the specimens, including
      simply advancing the guidewire through the atherosclerotic lesion, released
      thousands of fragments. The numbers of fragments in each size category increased
      with decreasing particle size. Positioning and deploying the Wallstent released
      an additional bolus of fragments similar to that released after balloon
      angioplasty. CONCLUSIONS: Ex vivo renal angioplasty releases thousands of
      atherosclerotic fragments of sufficient size to create vascular occlusions and
      initiate significant renal parenchymal damage. The results of renal angioplasty
      procedures could be improved by placing distal protection devices to prevent
      atheroembolization. CLINICAL RELEVANCE: Athero-emboli produce a local arteritis
      in the kidney and could cause substantial damage to the renal parenchyma. This
      report explores the quantity of athero-emboli released during ex vivo angioplasty
      and stenting of renal atheroma specimens. The number of emboli found in this ex
      vivo study suggest that the use of protection devices may be advisable to protect
      the end organ, as done with angioplasty of the carotid artery. Of necessity, this
      was an ex vivo study and direct application to the clinical setting will need
      further study. Fortunately, multi-center trials examining the value of protection
      devices are currently in progress.

PMID- 15944606
TI  - Laparoscopic aortic reinforcement and endovascular graft placement in swine: a
      new external wrap.
AB  - OBJECTIVE: To evaluate the feasibility, safety, and histological response of
      laparoscopic external aortic wrap implantation in conjunction with an
      endovascular stent/stent-graft placement in the infrarenal aorta in a porcine
      model. METHODS: Seven swine underwent laparoscopic retroperitoneal placement of a
      custom-made Dacron fabric wrap placed around the infrarenal aorta to create a
      landing zone for an endovascularly placed aortic stent/stent-graft. RESULTS:
      Technical success was achieved in all animals without any major complications.
      Follow-up ranged from 1 to 4 weeks. At necropsy, the external wraps were well
      incorporated into the adventitia, and the stents/stent-grafts were well
      incorporated into the intima. Small patches of medial necrosis of the aortic wall
      were observed in one animal in the stent model and in two animals in the stent
      graft model. There was no transmural necrosis observed. CONCLUSIONS This adjunct
      technique, an external wrap around the infrarenal aorta combined with
      endovascular grafting, is feasible and deserves further studies into how it may
      be used to facilitate endovascular repair of aortic aneurysms. CLINICAL
      RELEVANCE: We hypothesize that our new device could provide capability of
      altering the proximal neck morphology of abdominal aortic aneurysm and
      reinforcement to the aortic wall. This, in turn, could improve eligibility for
      endovascular aneurysm repair and prevent or treat type I endoleak and graft
      migration. Future investigations will involve evaluation of the long-term effect
      of the external aortic wrap on the integrity of the aortic wall in an animal
      model and testing the clinical usefulness of this new technique.

PMID- 15944607
TI  - Genetic analysis of polymorphisms in biologically relevant candidate genes in
      patients with abdominal aortic aneurysms.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by histologic
      signs of chronic inflammation, destructive remodeling of extracellular matrix,
      and depletion of vascular smooth muscle cells. We investigated the process of
      extracellular matrix remodeling by performing a genetic association study with
      polymorphisms in the genes for matrix metalloproteinases (MMPs), tissue
      inhibitors of metalloproteinases (TIMPs), and structural extracellular matrix
      molecules in AAA. Our hypothesis was that genetic variations in one or more of
      these genes contribute to greater or lesser activity of these gene products, and
      thereby contribute to susceptibility for developing AAAs. METHODS: DNA samples
      from 812 unrelated white subject (AAA, n = 387; controls, n = 425) were genotyped
      for 14 polymorphisms in 13 different candidate genes: MMP1(nt-1607), MMP2(nt
      955), MMP3(nt-1612), MMP9(nt-1562), MMP10(nt+180), MMP12(nt-82), MMP13(nt-77),
      TIMP1(nt+434), TIMP1(rs2070584), TIMP2(rs2009196), TIMP3(nt-1296), TGFB1(nt-509),
      ELN(nt+422), and COL3A1(nt+581). Odds ratios and P values adjusted for gender and
      country of origin using logistic regression and stratified by family history of
      AAA were calculated to test for association between genotype and disease status.
      Haplotype analysis was carried out for the two TIMP1 polymorphisms in male
      subjects. RESULTS: Analyses with one polymorphism per test without interactions
      showed an association with the two TIMP1 gene polymorphisms (nt+434, P = .0047;
      rs2070584, P = .015) in male subjects without a family history of AAA. The
      association remained significant when analyzing TIMP1 haplotypes (chi 2 P = .014
      and empirical P = .009). In addition, we found a significant interaction between
      the polymorphism and gender for MMP10 ( P = .037) in cases without a family
      history of AAA, as well as between the polymorphism and country of origin for ELN
      ( P = .0169) and TIMP3 ( P = .0023) in cases with a family history of AAA.
      CONCLUSIONS: These findings suggest that genetic variations in TIMP1, TIMP3,
      MMP10, and ELN genes may contribute to the pathogenesis of AAAs. Further work is
      needed to confirm the findings in an independent set of samples and to study the
      functional role of these variants in AAA. It is noteworthy that contrary to a
      previous study, we did not find an association between the MMP9 (nt-1562)
      polymorphism and AAA, suggesting genetic heterogeneity of the disease. CLINICAL
      RELEVANCE: Abdominal aortic aneurysms (AAAs) are an important cardiovascular
      disease, but the genetic and environmental risk factors, which contribute to
      individual's risk to develop an aneurysm, are poorly understood. Histologically,
      AAAs are characterized by signs of chronic inflammation, destructive remodeling
      of the extracellular matrix, and depletion of vascular smooth muscle cells. We
      hypothesized that genes involved in these events could harbor changes that make
      individuals more susceptible to developing aneurysms. This study identified
      significant genetic associations between DNA sequence changes in tissue inhibitor
      of metalloproteinase 1 (TIMP1), TIMP3, matrix metalloproteinase 10 (MMP10) and
      elastin (ELN) genes, and AAA. The results will require confirmation using an
      independent set of samples. After replication it is possible that these sequence
      changes in combination with other risk factors could be used in the future to
      identify individuals who are at increased risk for developing an AAA.

PMID- 15944608
TI  - Increased connexin43 expression in human saphenous veins in culture is associated
      with intimal hyperplasia.
AB  - OBJECTIVE: Intimal hyperplasia is a vascular remodelling process that occurs
      after a vascular injury. The mechanisms involved in intimal hyperplasia are
      proliferation, dedifferentiation, and migration of medial smooth muscle cells
      towards the subintimal space. We postulated that gap junctions, which coordinate
      physiologic processes such as cell growth and differentiation, might participate
      in the development of intimal hyperplasia. Connexin43 (Cx43) expression levels
      may be altered in intimal hyperplasia, and we therefore evaluated the regulated
      expression of Cx43 in human saphenous veins in culture in the presence or not of
      fluvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      activity. METHODS: Segments of harvested human saphenous veins, obtained at the
      time of bypass graft, were opened longitudinally with the luminal surface
      uppermost and maintained in culture for 14 days. Vein fragments were then
      processed for histologic examination, neointimal thickness measurements,
      immunocytochemistry, RNA, and proteins analysis. RESULTS: Of the four connexins
      (Cx37, 40, 43, and 45), we focused on Cx43 and Cx40, which we found by real-time
      polymerase chain reaction to be expressed in the saphenous vein because they are
      the predominant connexins expressed by smooth muscle cells and endothelial cells.
      After 14 days of culture, histomorphometric analysis showed a significant
      increase in the intimal thickness as observed during the process of intimal
      hyperplasia. A time-course analysis revealed a progressive upregulation of Cx43
      to reach a maximal increase of sixfold to eightfold at both transcript and
      protein levels after 14 days in culture. In contrast, the expression of Cx40,
      abundantly expressed in the endothelial cells, was not altered.
      Immunofluorescence showed a large increase in Cx43 within smooth muscle cell
      membranes of the media layer. The development of intimal hyperplasia in vitro was
      decreased in presence of fluvastatin and was associated with reduced Cx43
      expression. CONCLUSIONS: These data show that Cx43 is increased in vitro during
      the process of intimal hyperplasia and that fluvastatin could prevent this
      induction, supporting a critical role for Cx43-mediated gap-junctional
      communication in the human vein during the development of intimal hyperplasia.
      CLINICAL RELEVANCE: Stenosis due to intimal hyperplasia is the most common cause
      of failure of venous bypass grafts. To better understand the development of
      intimal hyperplasia, we used an ex vivo organ culture model to study saphenous
      veins harvested from patients undergoing a lower limb bypass surgery. In this
      model, the morphologic and functional integrity of the vessel wall is maintained
      and significant intimal hyperplasia development occurs after 14 days in culture.
      We have postulated that gap junctions, which coordinate physiologic processes
      such as cell growth and differentiation, may participate in the development of
      intimal hyperplasia. Indeed, intimal hyperplasia consists of proliferation and
      migration of smooth muscle cells into the subendothelial space. Intercellular
      communication is responsible for the direct transfer of ions and small molecules
      from one cell to the other through gap-junction channels found at cell-cell
      appositions. No study to date has evaluated whether gap junctional communication
      is involved in the process of intimal hyperplasia in humans. This assertion was
      investigated by using the aforementioned organ culture model of intimal
      hyperplasia in human saphenous veins, and our data support a critical role for
      Cx43-mediated gap junctional communication in human vein during the development
      of intimal hyperplasia.

PMID- 15944609
TI  - A minimally invasive approach to the treatment of aberrant splenic artery
      aneurysms: a report of two cases.
AB  - Symptomatic aneurysms of an aberrant splenic artery originating from the superior
      mesenteric artery are rare, with only five previous reports in the literature.
      The retropancreatic position renders their treatment more complex than aneurysms
      of orthotopic splenic arteries. Traditional treatment has been open surgical
      repair, with or without maintenance of flow through the splenic artery. We
      present our experience with two patients treated with a combination of coil
      embolization and laparoscopic occlusion of the splenic artery achieved by
      developing a retropancreatic plane and applying clips immediately distal to the
      aneurysm. This appears a promising minimally invasive technique to treat this
      rare condition. Long term follow up, however, is necessary to determine the
      applicability and results.

PMID- 15944610
TI  - Recurrent symptomatic aortic sac seroma after open abdominal aortic aneurysm
      repair.
AB  - The expansion of an abdominal aortic aneurysm sac after conventional repair has
      been rarely described. All cases in the literature have been associated with
      polytetrafluoroethylene grafts and perigraft seromas. We present a patient with a
      recurrent, symptomatic periaortic graft seroma after conventional repair. The
      etiology of this problem along with its potential increasing significance in the
      endovascular era is reviewed.

PMID- 15944611
TI  - The right gastroepiploic artery as an alternative inflow source in acute
      mesenteric ischemia.
AB  - Spontaneous and isolated dissection of the superior mesenteric artery is rare.
      This report describes a case treated with a new technique of right gastroepiploic
      artery to superior mesenteric artery bypass with a reversed saphenous vein graft,
      which has been patent for 6 years. This technique is an alternative approach in
      the setting of acute mesenteric ischemia.

PMID- 15944612
TI  - Sarcoidosis with double saccular abdominal aortic aneurysms.

PMID- 15944613
TI  - Surgical revascularization in the presence of a preserved primitive carotid
      basilar communication.
AB  - Anomalous arteries that connect the anterior and posterior cranial arterial
      systems are unusual variants that can severely alter normal patterns of cerebral
      blood flow. Persistent trigeminal, hypoglossal, otic, and proatlantal arteries
      have been described. This report illustrates the technical aspects of carotid
      endarterectomy with an ipsilateral preserved primitive carotid-basilar
      communication. Identification of the internal carotid and hypoglossal arteries,
      maintenance of cerebral perfusion, arteriotomy closure, preoperative imaging, the
      use of shunts, and reconstruction strategy are discussed. Preoperative
      angiography and detailed, individualized surgical strategy should be used to
      ensure a successful endarterectomy in patients with preserved primitive carotid
      basilar communications.

PMID- 15944615
TI  - Cardiovascular risk prevention in peripheral artery disease.
AB  - Patients with peripheral arterial disease are at greatly elevated risk for stroke
      and myocardial infarction and are six times more likely to die from
      cardiovascular causes than those without the disease. The available evidence
      supports the provision of an antiplatelet agent, a statin, and an angiotensin
      converting enzyme inhibitor for cardiovascular protection in these patients. When
      used together, these approaches are expected to produce a cumulative relative
      risk reduction of approximately 80%. Given the high baseline risk of this
      population and the effectiveness of these interventions, a combination of
      multiple drug therapies, in concert with aggressive lifestyle change and
      revascularization (where appropriate), can substantially reduce the burden of
      morbidity and mortality in patients with peripheral arterial disease.

PMID- 15944616
TI  - The ethics of odd ideas, good science, and academic freedom.

PMID- 15944617
TI  - Matrix molecule mRNA levels in the bursa and rotator cuff of patients with full
      thickness rotator cuff tears.
AB  - PURPOSE: The purpose of this study was to evaluate at the mRNA level a subset of
      extracellular matrix molecules relevant during healing and remodeling of rotator
      cuff tears. TYPE OF STUDY: Controlled laboratory study. METHODS: Bursal and
      rotator cuff tissue from the margin of the rotator cuff tear were harvested from
      10 patients (mean age, 57.5 +/- 7.3 years) undergoing surgical repair of full
      thickness rotator cuff tears. There were six male and four female patients with a
      mean duration of symptoms of 14.6 months (range, 2 to 60 months). The mean tear
      size was 4.4 cm. In addition, tissue was obtained from 6 cadaveric specimens with
      no gross evidence of rotator cuff tearing. Reverse transcription polymerase chain
      reaction (RT-PCR) was performed for type I, II, and III collagen, biglycan,
      decorin, and aggrecan, and normalized to the housekeeping gene GAPDH. RESULTS: RT
      PCR showed that both the bursa and rotator cuff margin had increased mRNA levels
      for type I and type III collagen in patients with full-thickness rotator cuff
      tears when compared with normal cadaveric controls. In addition, there was a
      significant decrease in decorin mRNA levels and an increase in aggrecan mRNA
      levels in the rotator cuff margin of torn rotator cuff tendons when compared with
      normal cadaveric controls. CONCLUSIONS: These results suggest that both the bursa
      and rotator cuff margin of patients with rotator cuff tears are actively
      remodeling after injury and that both tissues may potentially contribute to the
      healing process following repair. CLINICAL RELEVANCE: These findings may help
      clinicians determine what aspects of the repair process can be manipulated to
      affect optimal ruptured tendon repair.

PMID- 15944618
TI  - Arthroscopic versus open repair for traumatic anterior shoulder instability: a
      meta-analysis.
AB  - PURPOSE: The purpose of this study was to critically evaluate the literature to
      determine whether open or arthroscopic surgical repair for traumatic recurrent
      anterior shoulder instability results in a better outcome. TYPE OF STUDY: Meta
      analysis. METHODS: The search involved clinical studies in all languages in the
      MEDLINE database from 1966 to October 31, 2003. The following key words were
      used: (1) anterior shoulder instability, (2) Bankart lesion, (3) traumatic
      recurrent anterior shoulder instability, and (4) arthroscopic and open Bankart
      repair. All abstracts were reviewed and articles were included if there was a
      direct clinical comparison between arthroscopic and open repair for traumatic
      recurrent anterior shoulder instability. These articles were manually cross
      referenced for additional abstracts. The final group of articles was
      independently critically appraised and the following outcomes were extracted:
      recurrent instability, return to activity, reoperation rate, and cause of
      recurrence. RESULTS: The search terms resulted in 677, 183, 68, and 51 hits
      respectively. From these, 18 articles were determined to be eligible for full
      review including 2 foreign-language articles. Cross-referencing identified 2
      unpublished studies. Eleven studies were included in the final analysis: 1
      randomized trial, 2 pseudo-experimental designs, 4 prospective cohorts, 3
      retrospective studies, and 1 case control study. Pooled Mantel-Haenszel odds
      ratio for recurrent instability and return to activity were 2.04 ( P = .003; 95%
      confidence interval, 1.27, 3.29) and 2.85 ( P = .004; 95% confidence interval,
      1.40, 5.78), respectively, in favor of the open repair. CONCLUSIONS: Based on
      this meta-analysis, open repair has a more favorable outcome with respect to
      recurrence and return to activity. LEVEL OF EVIDENCE: Level III, Systematic
      Review of Level III (and II/I) Studies.

PMID- 15944619
TI  - Anterior capsulorrhaphy: an in vitro comparison of volume reduction--arthroscopic
      plication versus open capsular shift.
AB  - PURPOSE: The purpose of this study was to objectively compare volume reduction
      after arthroscopic plication and open lateral capsular shift. TYPE OF STUDY:
      Experimental cadaver study. METHODS: Fifteen fresh-frozen human cadaver shoulders
      were assigned to 1 of 2 groups: arthroscopic plication (n = 7) or open lateral
      capsular shift (n = 8). Initial capsular volume was measured by repeated
      injection of a viscous fatty acid sulfate solution and recorded for each
      specimen. Repeated measurements were taken after the procedure to determine
      volume reduction. RESULTS: Both procedures resulted in reduction of capsular
      volume. The arthroscopic plication resulted in a 22.8% volume reduction and the
      open lateral capsular shift resulted in a 49.9% volume reduction. Comparison of
      the 2 procedures revealed significant volume reduction after open lateral
      capsular shift compared with arthroscopic plication (P = .00001). Repeated
      measurements confirmed that the injection technique was valid and reproducible.
      CONCLUSIONS: The lateral capsular shift resulted in significantly greater volume
      reduction compared with arthroscopic plication. Based on these results, we
      recommend an open lateral-based capsular shift for patients with multidirectional
      instability in which a larger capsular shift is required. However, additional
      plication sutures may allow for an even further reduction in volume. The amount
      of volume reduction required to eliminate instability still remains unknown for
      patients with shoulder instability caused by capsular laxity. LEVEL OF EVIDENCE:
      Level IV Case Series, in vitro anatomic comparison of 2 surgical procedures.

PMID- 15944620
TI  - Axillary nerve monitoring during arthroscopic shoulder stabilization.
AB  - PURPOSE: This study evaluated the ability of a novel intraoperative
      neurophysiologic monitoring method used to locate the axillary nerve, predict
      relative capsule thickness, and identify impending injury to the axillary nerve
      during arthroscopic thermal capsulorrhaphy of the shoulder. TYPE OF STUDY:
      Prospective cohort study. METHODS: Twenty consecutive patients with glenohumeral
      instability were monitored prospectively during arthroscopic shoulder surgery.
      Axillary nerve mapping and relative capsule thickness estimates were recorded
      before the stabilization portion of the procedure. During labral repair and/or
      thermal capsulorrhaphy, continuous and spontaneous electromyography recorded
      nerve activity. In addition, trans-spinal motor-evoked potentials of the fourth
      and fifth cervical roots and brachial plexus electrical stimulation, provided
      real-time information about nerve integrity. RESULTS: Axillary nerve mapping and
      relative capsule thickness were recorded in all patients. Continuous axillary
      nerve monitoring was successfully performed in all patients. Eleven of the 20
      patients underwent thermal capsulorrhaphy alone or in combination with
      arthroscopic labral repair. Nine patients underwent arthroscopic labral repair
      alone. In 4 of the 11 patients who underwent thermal capsulorrhaphy, excessive
      spontaneous neurotonic electromyographic activity was noted, thereby altering the
      pattern of heat application by the surgeon. In 1 of these 4 patients, a small
      increase in the motor latency was noted after the procedure but no clinical
      deficit was observed. There were no neuromonitoring or clinical neurologic
      changes observed in the labral repair group without thermal application. At last
      follow-up, no patient in either group had any clinical evidence of nerve injury
      or complications from neurophysiologic monitoring. CONCLUSIONS: We successfully
      evaluated the use of intraoperative nerve monitoring to identify axillary nerve
      position, capsule thickness, and provide real-time identification of impending
      nerve injury and function during shoulder thermal capsulorrhaphy. The use of
      intraoperative nerve monitoring altered the heat application technique in 4 of 11
      patients and may have prevented nerve injury. LEVEL OF EVIDENCE: Level II,
      prospective cohort study.

PMID- 15944621
TI  - Exploration of glenohumeral instability under anesthesia: the shoulder jerk test.
AB  - PURPOSE: The purpose of this study was to develop a new protocol for the
      performance of jerk tests under anesthesia, and to study its correlation to intra
      articular pathology and the diagnosis of a lax or unstable shoulder. TYPE OF
      STUDY: Prospective controlled study. METHODS: We performed a systematic
      examination, in the office as well as under anesthesia, of 300 patients (600
      shoulders) divided into 3 homogeneous groups: 100 presented with instability
      resulting from recurrent dislocation of one or both shoulders, 100 presented with
      alternative shoulder symptomatology without signs of instability, and a further
      100 underwent surgery for other locomotor system pathologies. RESULTS: The
      following statistical sensitivity values were found: anterior jerk, 90.7%;
      inferior jerk, 96.2%. Correct interpretation of jerk tests under anesthesia will
      help us decide the type and scope of required surgical therapy. LEVEL OF
      EVIDENCE: Level III, Diagnostic Study of Nonconsecutive Patients.

PMID- 15944622
TI  - Recovery after arthroscopic subacromial decompression: prognostic value of the
      subacromial injection test.
AB  - PURPOSE: To evaluate the use of a steroid/local anesthetic subacromial injection
      as a prognostic tool for patient recovery following arthroscopic subacromial
      decompression (ASD). TYPE OF STUDY: Prospective cohort study. METHODS: A local
      anesthetic/steroid subacromial injection was administered to all patients with a
      clinical diagnosis of subacromial impingement syndrome. In the event of a
      negative result to the injection test, the diagnosis was confirmed by computed
      tomographic arthrography or magnetic resonance imaging. All patients underwent
      standard ASD. The outcome was assessed using the Constant score, performed
      preoperatively, at 3 weeks, 3 months, and at discharge. The eventual functional
      outcome was correlated with the results of the injection test and the operative
      findings. RESULTS: There were 101 patients (53 male, 48 female), with a mean age
      of 52 years (range, 21 to 77 years) in the study. Patients were followed-up for a
      mean of 14 months (range, 3 to 24 months). All patients had an impingement lesion
      noted at arthroscopy. The mean preoperative Constant score for the entire group
      was 48 points (range, 20-67) with a postoperative mean of 81 (range, 46-98).
      Sixteen patients had a negative preoperative injection test. The mean improvement
      in this group was 21 points (47 rising to 68) compared with 35 points (48 to 83)
      in the positive group (P < .05, Mann-Whitney U test). The groups were otherwise
      similar for age, gender, and operative findings. CONCLUSIONS: The steroid/local
      anesthetic injection test is a useful tool both diagnostically and prognostically
      in patients with subacromial impingement syndrome. In patients with a confirmed
      diagnosis but a negative test there is still a significant improvement in the
      postoperative Constant score, but this is of a lesser degree than in those with a
      positive result to local anesthetic injection. LEVEL OF EVIDENCE: Level III,
      Diagnostic Study of Nonconsecutive Patients.

PMID- 15944623
TI  - Long-term follow-up of open and endoscopic Hohmann procedures for lateral
      epicondylitis.
AB  - PURPOSE: The long-term outcome of this new endoscopic technique was compared with
      that of the classical open Hohmann procedure. TYPE OF STUDY: Retrospective cohort
      study. METHODS: During 1992 and 1995, 37 patients were surgically treated with
      the Hohmann procedure after failed intensive conservative treatment. At an
      average of 92 months after the operation, 30 patients (81%) could be clinically
      re-examined and were evaluated with a standard questionnaire including the scores
      of Roles and Maudsley and Morrey et al. RESULTS: Twenty of these patients were
      treated endoscopically and 10 with the open technique. There were no differences
      in demographic data between the 2 groups. At follow-up in both groups, similar
      results were seen for the function of the elbow, the scores of Roles and Maudsley
      and Morrey et al., the subjective rating of pain and function of the elbow, and
      complication rate. The results in the score of Morrey showed an average scoring
      of 93.2 for the endoscopic group and 87.5 for the open group (P > .05).
      CONCLUSIONS: The endoscopic technique showed results comparable to the open
      technique and can therefore be recommended for wider surgical use so as to learn
      more details concerning possible complications and results of the new technique.
      LEVEL OF EVIDENCE: Level III, retrospective cohort study.

PMID- 15944624
TI  - Endoscopic release of the ulnar nerve at the elbow using the Agee device: a
      cadaveric study.
AB  - PURPOSE: The purpose of this study was to assess the safety and efficacy of the
      Agee endoscopic system (3M, Orthopedic Products, St. Paul, MN) for ulnar nerve
      decompression at the elbow. TYPE OF STUDY: A cadaveric study. METHODS: The ulnar
      nerve was identified through a 3-cm longitudinal incision between the medial
      epicondyle and olecranon. A release of the ulnar nerve was performed with the
      Agee device under endoscopic magnification. A complete open assessment of the
      ulnar nerve, its branching, and structures divided was performed under loupe
      magnification. RESULTS: In all 6 cadaveric specimens, the arcade of Struthers,
      the cubital tunnel retinaculum, and the flexor carpi ulnaris aponeurosis were
      completely divided. In all specimens, the ulnar nerve and all motor and capsular
      branches were preserved. CONCLUSIONS: This study has demonstrated that the Agee
      endoscopic ulnar nerve decompression at the elbow is both safe and effective in a
      cadaveric model. CLINICAL RELEVANCE: This cadaveric study shows that a surgical
      decompression of the ulnar nerve can be safely and effectively performed with a
      single endoscopic portal using the Agee device.

PMID- 15944625
TI  - Thirty-five years of follow-up of anterior cruciate ligament-deficient knees in
      high-level athletes.
AB  - PURPOSE: The incidence and progression of osteoarthritis over a time period of 35
      years following anterior cruciate ligament (ACL) disruption in high-level
      athletes has not been clearly determined. Our study examined this. TYPE OF STUDY:
      Retrospective cohort clinical study. METHODS: Following a central guideline,
      between March 1963 and December 1965, all 19 athletes in the Olympic program of
      former East Germany who sustained an ACL injury were treated without
      reconstruction. In a retrospective cohort study, the clinical results were
      evaluated for all patients from 1975 and 1985 and for 17 of the 19 patients in
      2000; 18 of the 19 patients were examined arthroscopically in 1985. RESULTS: All
      patients were able to return to sports after a period of 6 to 14 weeks. Ten years
      after the injury, meniscectomy had to be performed in 15 of the 19 patients
      (79%). The medial meniscus was affected in 13 patients (68%) and the lateral in 7
      (37%); 20 years after the injury, meniscectomy was necessary in 18 of the 19
      patients (95%). In 1985, in 18 of the 19 knees, arthroscopy was performed and 13
      patients (68%) had a grade 4 chondral lesion. Ten total knee replacements had to
      be performed until the end of the year 2000. CONCLUSIONS: We conclude that,
      despite the possibility of return to high-level activity with a definitive
      unstable knee, this will lead in 95% of cases to meniscal and cartilage damage
      over the next 20 years. In addition, cartilage damage and progressive
      osteoarthritis will occur and patients will have a high risk of becoming a
      candidate for further total joint replacement. LEVEL OF EVIDENCE: Level IV.

PMID- 15944626
TI  - Central versus peripheral tibial screw placement in hamstring anterior cruciate
      ligament reconstruction: in vitro biomechanics.
AB  - PURPOSE: To determine whether a cone-shaped interference screw positioned
      centrally during tibial fixation in hamstring anterior cruciate ligament (ACL)
      reconstruction was equal to or better than a peripheral position in terms of
      stiffness, yield load, ultimate load, and mode of failure. TYPE OF STUDY:
      Randomized matched-pair biomechanical pullout study. METHODS: One of each of 7
      matched pairs of human cadaveric tendon in porcine tibia with titanium cone
      shaped screws were randomly allocated to either the peripheral or central group.
      Bone tunnels were drilled 45 degrees to the long axis of the tibia, akin to
      standard ACL reconstruction. Tunnel diameter was matched to tendon diameter and a
      screw 1 mm larger than tunnel diameter was inserted. A Universal Materials
      Testing Machine (Hounsfield Testing Equipment, Horsham, PA) was used to pull in
      the line of the tendon. Tendons were inspected after construct disassembly.
      RESULTS: The central screw configuration showed significantly higher stiffness (P
      = .0085), yield load (P = .0135), and ultimate load (P = .0075). The mode of
      failure in the peripheral screw position was slippage at the screw-tendon
      interface in all cases. In the central group, 87.5% of cases had a breakage in
      the tendon and 12.5% had slippage at the tendon-bone interface. CONCLUSIONS:
      Central interference screw fixation of soft-tissue ACL reconstruction offers
      superior fixation strength and stiffness in single pullout mode when compared
      with peripheral interference screw fixation. Failure in the central group was
      mostly by tendon breakage, suggesting that a larger difference may be exhibited
      by the central over the peripheral fixation than demonstrated in this study.
      CLINICAL RELEVANCE: Central interference screw fixation compared with peripheral
      fixation may allow greater confidence in early rehabilitation and reduced
      clinical failure rates in the long term.

PMID- 15944627
TI  - The natural history of a bioabsorbable interference screw used for anterior
      cruciate ligament reconstruction with a 4-strand hamstring technique.
AB  - PURPOSE: The purpose of this study was to assess radiologically the rate of
      absorption of the Arthrex poly L-lactide bioabsorbable interference screw
      (Arthrex, Naples, FL) used in anterior cruciate ligament reconstruction with a 4
      strand hamstring technique. TYPE OF STUDY: Case series. METHODS: Eight sequential
      patients undergoing anterior cruciate ligament reconstruction with a 4-strand
      hamstring technique were assessed with magnetic resonance imaging (MRI) scans at
      1, 2, and 4 years postoperatively. RESULTS: There was no radiologic evidence of
      absorption of the screw on any of the scans. The MRI appearance remained
      essentially unchanged from 1 to 4 years with the exception of the presence of a
      small cyst in the tibial tunnel of one of the patients. No edema was seen
      associated with the tibial tunnel in any of our patients. CONCLUSIONS: There are
      several quoted theoretical advantages to using bioabsorbable screws. The rate of
      absorption is dependent on material, weight, and degree of crystallization. In
      our series using an amorphous low crystallization poly L-lactide screw, there was
      no evidence of any progression to absorption 4 years after implantation. This may
      be because all series quoted to date look at absorption using a bone-patellar
      tendon-bone graft. LEVEL OF EVIDENCE: Level IV.

PMID- 15944628
TI  - The graft/tunnel angles in posterior cruciate ligament reconstruction: a
      cadaveric comparison of two techniques for femoral tunnel placement.
AB  - PURPOSE: In posterior cruciate ligament reconstruction, the tibial tunnel/graft
      angle (or killer turn) has been implicated in graft failure when using
      transtibial tunnel placement. The graft/femoral tunnel angle (or critical corner)
      can also contribute to shear stress and early graft failure. The purpose of this
      study was to quantitate the killer turn angle in flexion and extension and to
      compare critical corner angles using outside-in and inside-out techniques for
      femoral tunnel placement. TYPE OF STUDY: A cadaveric, biomechanical comparison.
      METHODS: One transtibial tunnel and 2 femoral tunnels were marked with guidewires
      in 9 fresh-frozen cadaveric knees. The killer turn and the 2 critical corner
      angles were measured at 90 degrees of flexion and full extension on fluoroscopic
      images. Results were analyzed using a Student t test with paired data. RESULTS:
      The average killer turn was 70 degrees +/- 12 degrees and 78 degrees +/- 7
      degrees in flexion and extension, respectively. Knee extension significantly
      increased the killer turn angle (P = .048). The average critical corner was 50
      degrees +/- 16 degrees and -14 degrees +/- 18 degrees with the outside-in
      technique versus 87 degrees +/- 8 degrees and 27 degrees +/- 14 degrees with the
      inside-out technique in flexion and extension, respectively. The inside-out
      technique significantly increased the critical corner in flexion (P = .00007) and
      extension (P = .00005). At 90 degrees of flexion, the critical corner angle using
      the inside-out technique significantly exceeded the killer turn angle (P = .003).
      CONCLUSIONS: We recommend the outside-in technique for femoral tunnel placement
      to reduce the graft/femoral tunnel angle. Using the inside-out technique can
      significantly sharpen the critical corner, causing it to exceed the killer turn
      in flexion. CLINICAL RELEVANCE: This study indicates that significantly lower
      graft/femoral tunnel angles can be obtained when using the outside-in technique
      for femoral tunnel placement when compared with the inside-out technique. This
      may translate to lower rates of graft failure in clinical application, although
      further clinical studies are needed.

PMID- 15944629
TI  - Dynamic evaluation of contact pressure and the effects of graft harvest with
      subsequent lateral release at osteochondral donor sites in the knee.
AB  - PURPOSE: To dynamically evaluate contact pressure about the periphery of the
      lateral femoral condyle in intact knees, to qualify the effects of osteochondral
      donor graft harvest on this contact pressure, and to quantify the effects of
      lateral release on contact pressure after graft harvest. TYPE OF STUDY: Cadaveric
      analysis. METHODS: Digital electronic pressure-sensing cells were used to measure
      contact pressure over the periphery of the lateral femoral condyle in 10 fresh
      frozen knee specimens. Nonweightbearing resistive extension was simulated as the
      knees were placed through a functional range of motion. Dynamic pressure readings
      were evaluated over intact cartilage, around the rims of four 5-mm osteochondral
      defects, and after lateral release. RESULTS: The pressure cells were all
      subjected to contact pressures as the knees were placed through a functional
      range of motion. Average maximal contact pressure progressed distally as the
      knees were flexed. The creation of 5-mm osteochondral defects did not lead to a
      significant increase in rim stress concentration over the surrounding cartilage.
      Lateral release resulted in small decreases in contact pressure over the
      osteochondral defects. CONCLUSIONS: The creation of 5-mm donor defects about the
      lateral aspect of the lateral femoral condyle does not lead to significant
      alterations in local contact pressure. CLINICAL RELEVANCE: Our biomechanical
      findings may have important implications relating to cartilage restoration using
      osteochondral autografting procedures. Donor-site morbidity may be minimized if
      donor-site defects are limited to 5 mm and smaller.

PMID- 15944630
TI  - Arthroscopic evaluation of the popliteus: clues to posterolateral laxity.
AB  - PURPOSE: In cases of posterolateral laxity with abnormally increased external
      rotation of the tibia, the arthroscopically visualized portion of the popliteal
      tendon can have a different appearance. The purpose of this study was to
      determine whether laxity at the nonvisualized femoral insertion of the popliteus
      tendon or the popliteal fibular ligament caused the altered appearance. TYPE OF
      STUDY: Fresh cadaveric selective cutting. METHODS: Ten cadaveric specimens with
      normal appearing popliteal tendon were examined arthroscopically. In 5 specimens,
      partial and complete detachment of the femoral insertion was performed and the
      appearance visualized arthroscopically. In 5 specimens, the popliteal fibular
      ligament was detached and the popliteal tendon visualized arthroscopically.
      RESULTS: Laxity at the nonvisualized femoral insertion of the popliteus tendon
      leads to a different appearance of the arthroscopic view of the popliteal tendon.
      This altered appearance was determined by an intact popliteal fibular ligament. A
      different alternation occurs when the popliteal fibular ligament is resected.
      CONCLUSIONS: Differences in the arthroscopic view of the popliteal tendon may be
      important clues to the cause of increased external rotation of the tibia.
      CLINICAL RELEVANCE: This study presents a method for arthroscopists to observe
      and evaluate the popliteus tendon and the posterior lateral corner of the knee in
      relation to external rotation of the tibia in symptomatic and asymptomatic
      posterior lateral rotation.

PMID- 15944631
TI  - Deep venous thrombosis after knee arthroscopy: a meta-analysis.
AB  - PURPOSE: To better establish the incidence of deep venous thrombosis (DVT) after
      knee arthroscopy without prophylaxis. TYPE OF STUDY: Meta-analysis. METHODS: A
      MEDLINE search was performed to find published English-language studies of DVT
      following knee arthroscopy. Strict inclusion criteria required any investigation
      included for analysis to (1) be prospective, (2) include a population not given
      any antithrombotic prophylaxis, (3) perform universal screening of the lower
      extremity venous system using either ultrasound or venography, and (4) include a
      discrete population limited to unilateral arthroscopic knee surgery, exclusive of
      ligament surgery or open procedures. The results of the venographic studies were
      given additional weight mathematically to account for the increased sensitivity
      of this imaging modality compared with ultrasound in detecting DVT in
      asymptomatic lower extremities. RESULTS: The unprophylaxed patient populations in
      the 6 studies that met inclusion criteria ranged from 64 to 184 patients, and
      totaled 684. The total incidence rate of DVT in each study ranged from 3.1% to
      17.9%, whereas the incidence rate of proximal DVT ranged from none detected to
      4.9%. The total DVT rate was not related to the method of DVT detection, whereas
      proximal DVT was only noted in the 2 studies using contrast venography. Combining
      the 6 studies yields a total DVT incidence of 9.9% (95% confidence interval, 8.1%
      11.7%), and a proximal DVT incidence of 2.1% (95% confidence interval, 1.2%
      3.0%). CONCLUSIONS: DVT following knee arthroscopy is a consistent finding in
      studies of unprophylaxed patients when routine screening using ultrasound or
      contrast venography is used. Current data suggest an overall DVT rate of 9.9% and
      a proximal DVT rate of 2.1% after knee arthroscopy without antithrombosis
      prophylaxis. LEVEL OF EVIDENCE: Level II, Systematic Review of Levels I and II
      Diagnostic Studies.

PMID- 15944632
TI  - A study of effectiveness of knee arthroscopy after knee arthroplasty.
AB  - PURPOSE: The purpose of this study was to investigate the outcome of arthroscopy
      in painful knee arthroplasty without evidence of infection, fracture, wear, and
      component loosening or malposition that had been refractory to conservative
      treatment. In addition, a literature review of 498 cases (MEDLINE 1966 to 2002)
      was performed. TYPE OF STUDY: Case series. METHODS: From 1997 to 2000, 27
      patients (20 women, 7 men) had undergone arthroscopies because of poor results
      following total knee arthroplasty. Before the operation, the patients had
      suffered symptoms for an average of 11 months (range, 3 to 41 months). The
      average onset of symptoms after knee arthroplasty was 26 months (range, 3 to 59
      months). The average patient age was 70 years (range, 42 to 81 years) and the
      average follow-up was 34 months (range, 24 to 52 months). At the initial
      operation, 19 patients had received total condylar surface replacement and 8 had
      received hemireplacement. Patients were evaluated using the Knee Society rating
      system. A review of the literature was performed by initial identification of the
      articles from a MEDLINE database followed by the use of cross references.
      RESULTS: All of the patients were available for follow-up. Eighteen of the 27
      procedures resulted in an improvement in the patient's knee score. The average
      Knee Society ratings increased from 71 points before arthroscopy to 85 at follow
      up for the knee score. The average functional scores were 69 and 83 points,
      respectively. The Knee Society pain score improved from 32 to 41 points. Nine
      patients underwent a subsequent open revision after arthroscopic diagnosis or
      treatment. Operative diagnoses included arthrofibrosis, impinging hypertrophic
      synovitis, impinging posterior cruciate ligament stump, prosthesis loosening or
      wear, symptomatic pseudomeniscus, an infrapatellar spur, and meniscal rupture.
      There was 1 infection as a complication associated with the arthroscopic
      procedure. CONCLUSIONS: Arthroscopic treatment of painful knee arthroplasty
      provides reliable expectations for improvement in function, decrease in pain, and
      improvement in knee scores for most patients. LEVEL OF EVIDENCE: Level IV, Case
      Series.

PMID- 15944633
TI  - Video informed consent improves knee arthroscopy patient comprehension.
AB  - PURPOSE: The purpose of this study was to test the hypothesis that video informed
      consent improves knee arthroscopy patient comprehension and satisfaction compared
      with traditional verbal informed consent. TYPE OF STUDY: Prospective, randomized
      controlled trial. METHODS: Consecutive patients having informed consent in
      preparation for knee arthroscopy by a single surgeon were stratified by
      educational level < or =12th grade or greater than 12th grade, then randomized to
      video or traditional verbal informed consent groups. Immediately after the
      informed consent process, patients completed an outcome questionnaire evaluating
      comprehension and satisfaction. RESULTS: Patients in the video group showed
      significantly higher comprehension (78.5%) than patients in the verbal group
      (65.4%) (P = .00001). In the subgroup with < or = 12th grade education level, the
      video patients scored 73.1% comprehension and the verbal patients only 54.2% (P =
      .0011). In the subgroup with greater than 12th grade education level, the video
      patients scored 82.3% and the verbal patients scored 72.2% (P = .0002). There was
      no significant difference in subjective self-assessment of satisfaction between
      groups. CONCLUSIONS: Video informed consent improves knee arthroscopy patient
      comprehension compared with traditional verbal informed consent. LEVEL OF
      EVIDENCE: Level I.

PMID- 15944634
TI  - Arthroscopic meniscal repair using the BioStinger.
AB  - PURPOSE: Biodegradable devices are available for all-inside meniscal repairs. One
      device, the BioStinger (Linvatec, Largo, FL), is made of molded poly-L-lactic
      acid. The purpose of this study was to evaluate the effectiveness of and any
      adverse events associated with meniscus repair using this device. TYPE OF STUDY:
      Nonrandomized prospective cohort study. METHODS: A prospective, consecutive, 3
      center meniscal repair series using BioStingers (group 1), vertical inside-out
      sutures (group 2), or hybrid repairs combining BioStingers and sutures (group 3)
      was studied. Lysholm, Tegner, Cincinnati, and IKDC activity scores were obtained
      and clinical outcomes and adverse events documented. RESULTS: There were 85
      patients who underwent 89 meniscus repairs with an average 26.5 months of follow
      up. There were 47 BioStinger repairs (group 1), 29 suture repairs (group 2), and
      13 hybrid repairs (group 3). The tear length was statistically greater for the
      hybrid repair group (P < .5). There were 73 repairs associated with anterior
      cruciate ligament reconstructions and 12 repeat arthroscopies were performed.
      Meniscal healing failed in 6 knees (4 in group 1, 0 in group 2, and 2 in group
      3). The meniscal healing failed in 7% of those associated with anterior cruciate
      ligament reconstructions. Mean Tegner scores improved from 2.8 to 6.3, the final
      IKDC activity score was 3.2 out of 4, the mean Lysholm score improved from 51 to
      88, and the mean Cincinnati score improved from 44 to 84. Two BioStinger repair
      cases had joint-line tenderness from device migration confirmed by magnetic
      resonance imaging. No tenting of the skin or articular cartilage scuffing was
      observed. CONCLUSIONS: The success rate for the 29 suture repairs was 100% and
      for the 47 BioStinger repairs was 91%. These preliminary results are consistent
      with other repair techniques. LEVEL OF EVIDENCE: Level II, Therapeutic
      Prospective Cohort Study.

PMID- 15944635
TI  - The use of arthroscopic thermal shrinkage to treat chronic lateral ankle
      instability in young athletes.
AB  - PURPOSE: The aim of this study was to evaluate the preliminary results of
      arthroscopic thermal capsular shrinkage performed for chronic lateral ankle
      instability in soccer players. TYPE OF STUDY: Case series. METHODS: We reviewed
      22 male soccer players (average age, 18 years) with chronic lateral ankle
      instability who underwent arthroscopic thermal shrinkage between 1997 and 1998.
      The only exclusion criterion for this study was the failure of previous surgery.
      Before surgery, all patients had participated in a physical rehabilitation
      program consisting of peroneal strengthening exercises and proprioceptive
      training for several months, without any relief of their symptoms. All patients
      were characterized by repeated episodes of giving way, a positive anterior drawer
      sign, and positive stress radiographs. The stress radiographs consisted of a
      sagittal stress and talar tilt by the TELOS device (Fallston, MD). The Karlsson
      and Peterson ankle function scoring scale was used to assess these patients for
      their current activity level as well as activity before surgery. RESULTS:
      Patients were reviewed at a mean of 42 months (range, 32 to 56 months); 19
      patients (86.3%) reported a good or excellent functional outcome as assessed by
      the Karlsson and Peterson ankle function scoring scale. Eighteen of the 22
      patients presented no evidence of ankle instability on physical examination or on
      stress radiographs. Only 1 patient was not able to return to his previous level
      of sports activity and complained of ankle instability when walking on uneven
      ground. CONCLUSIONS: This study suggests that arthroscopic thermal capsular
      shrinkage is a valid and safe procedure for treatment of chronic lateral ankle
      instability. Longer follow-up is needed, however, to see how these results may
      change with time in high-demand athletes. LEVEL OF EVIDENCE: Level IV.

PMID- 15944636
TI  - Cubital tunnel syndrome in adolescent baseball players: a report of six cases
      with 3- to 5-year follow-up.
AB  - In this case report, we describe the clinical features and surgical outcome of
      cubital tunnel syndrome in adolescent baseball players. Two infielders, 2
      pitchers, and 2 catchers who suffered cubital tunnel syndrome during adolescence
      (average age, 14 years) were surgically treated. Symptoms of medial elbow pain
      first appeared during throwing in competition games in summer or autumn seasons.
      After the onset, they suffered limitation of elbow extension and weakness on
      grabbing balls. They could not throw because of recurrent medial elbow pain.
      Laxity of the medial collateral ligament was not detected by stress radiography.
      Duration of symptoms from the onset to surgery was less than 6 months for 2
      patients, 1 year for 2, and longer than 2 years for 2 patients. Anterior
      subcutaneous transposition of the ulnar nerve relieved symptoms up to 3.3
      postoperative years. Medial protrusion of the triceps muscle was observed to
      cause irritation of the ulnar nerve. Fibrosis surrounding the ulnar nerve was
      observed without pseudoneuroma. Throwing performance returned completely to
      competitive level in 5 months postoperatively in 5 of 6 patients. Early diagnosis
      of cubital tunnel syndrome in adolescent baseball players is very important.
      Anterior subcutaneous transposition of the ulnar nerve relieves symptoms and
      restores throwing function.

PMID- 15944637
TI  - Medial collateral ligament bursitis in a 12-year-old girl.
AB  - A 12-year-old female athlete, training for an international career in pentathlon,
      was referred to our clinic because of 2 years of recurrent localized swelling and
      activity-related pain in the medial aspect of her right knee, since falling from
      a horse and hitting her knees on the ground. She had been examined by a number of
      doctors over this period and treated with physiotherapy without a proper
      diagnosis and with no improvement. She could run only very limited distances
      before excruciating pain and swelling, and she had to abandon participation in
      competitions. During rest, the swelling decreased but never disappeared entirely.
      Clinical examination revealed minor effusion and localized tenderness on
      palpation around the medial joint line. Magnetic resonance imaging showed fluid
      between the medial capsule and medial collateral ligament, but could not identify
      any connection to the joint. Arthroscopy revealed a cleavage in the posterior
      medial joint capsule, superior and close to the medial meniscus, that was
      connected to the medial collateral ligament bursa. The cleavage was simply
      expanded, which emptied the bursa, followed by compression bandage and ice for 2
      weeks. An immediate positive effect was observed and she could run pain free
      without swelling within 3 weeks of surgery. Six months after surgery, there has
      been no recurrence. To our knowledge, this is the first time this injury has been
      described in a child.

PMID- 15944638
TI  - Seventeen-year follow-up of a reattachment of a nonunited anterior tibial spine
      avulsion fracture.
AB  - Seventeen years ago we treated a nonunited avulsion fracture of the anterior
      tibial spine with open reduction and pull-out wires. When the patient was 9 years
      old, she fell and bruised her left knee. The knee was immobilized for a month in
      a long cast. When she was 24 years old, she felt severe knee pain and giving way
      after playing tennis 1 month before her first visit to our hospital. She
      complained of knee pain, giving way, locking, and 15 degrees loss of knee
      extension. Radiographs showed a large nonunited fragment at the intercondylar
      eminence of the tibia. She underwent a reattachment surgery. When she was re
      evaluated 17 years after surgery, she had no pain, no giving way, no locking, and
      no loss of knee extension. On physical examination, there was no instability.
      Plain anteroposterior and lateral radiographs showed a well-united fragment of
      the anterior tibial spine. In conclusion, the open reduction for knee pain,
      giving way, locking, and loss of knee extension caused by nonunion of avulsion of
      the anterior tibial spine yielded satisfactory results. We believe that in cases
      of nonunited anterior tibial spine fractures it is necessary to attempt to secure
      the anterior cruciate ligament in an anatomic position.

PMID- 15944639
TI  - Clustered localized pigmented villonodular synovitis.
AB  - The localized form of pigmented villonodular synovitis (PVNS) is a rare
      pathologic entity characterized by limited involvement of the synovium. In the
      knee joint, which is the most commonly affected joint, the disorder generally
      presents as a single nodular lesion, or rarely as 2 or 3 multiple nodular lesions
      into the joint. We report 2 cases of localized PVNS in which multiple nodules
      were clustered in a limited patella fat pad area. Clustered, multiple nodular
      lesions in a limited area suggested to us to consider a variant of localized
      forms.

PMID- 15944640
TI  - Complications following hamstring anterior cruciate ligament reconstruction with
      femoral cross-pin fixation.
AB  - Cross-pin fixation of hamstring grafts for anterior cruciate ligament
      reconstruction was developed with hopes of improving on potential problems
      associated with interference screw and button fixation methods. However, cross
      pins are a relatively new method of graft fixation and there are limited data on
      this technique. We report 2 cases in which reoperation was necessary after
      complications associated with cross-pin fixation. In one case, the cross-pin was
      left too proud and in the other it penetrated the medial side of the femur and
      was prominent. Surgeons who use cross-pin fixation should pay close attention so
      as not to leave the cross-pin proud laterally or medially to avoid the necessity
      of reoperation for hardware removal.

PMID- 15944641
TI  - Traumatic rupture of the coracoacromial ligament.
AB  - This is a case report of an arthroscopically diagnosed injury to the
      coracoacromial ligament at the undersurface of the acromion. To our knowledge,
      this has not been previously described. Traumatic avulsion of this ligament may
      represent a source of subacromial impingement that has not been recognized.

PMID- 15944642
TI  - Arthroscopic transfer of the long head biceps to the conjoint tendon.
AB  - Pathology of the biceps tendon is often a factor in the etiology of shoulder
      pain. However, diagnosis and treatment of such pathology remains controversial.
      When conservative management fails to relieve symptoms, surgical options include
      tenotomy or tenodesis. Tenotomy has provided excellent results with regard to
      local pain relief, but a potential cosmetic deformity and occasional painful
      cramping are common in younger patients. Tenodesis has also had high failure
      rates resulting from persistent local pain. We have used an all-arthroscopic
      technique for transfer of the long-head biceps to the conjoint tendon instead of
      traditional tenodesis. We believe that this transfer more closely recreates the
      normal axis of the biceps muscle and may offer improved results over conventional
      tenodesis.

PMID- 15944643
TI  - Rotator interval closure after arthroscopic capsulolabral repair: a technical
      variation.
AB  - Rotator interval tear is one of the lesions identified in patients with
      glenohumeral instability. We present our technique for arthroscopic interval
      capsule repair. After having performed Bankart reconstruction, we pull the
      anterosuperior cannula back some millimeters and introduce a Penetrator suture
      retriever forceps (Arthrex, Naples, FL) through the upper interval capsule into
      the joint. Then we also remove some millimeters of the anterior cannula and
      introduce a suture passer (Spectrum; Linvatec, Largo, FL) loaded with a
      monofilament suture through the lower interval capsule. The suture is pushed into
      the joint and, using the Penetrator suture retriever forceps, we retrieve it out
      of the joint. This suture is replaced if desired by a permanent braided suture.
      Next, a suture passer (Arthrex) advances the end of the suture from the
      anterosuperior portal into the joint. The suture is retrieved out of the joint
      from the anterior cannula with a crochet hook. We tie the suture down the
      anterior cannula to close the anterior capsule. Because we use cannulas, we can
      use a sliding knot. The degree of tightening can be observed directly under
      arthroscopic view but the knot is outside of the capsule. We believe that this
      method is easy, effective, and reproducible.

PMID- 15944644
TI  - Arthroscopic labral repair and capsular shift of the glenohumeral joint:
      technical pearls for a multiple pleated plication through a single working
      portal.
AB  - The arthroscopic treatment of shoulder instability is becoming increasingly
      popular with recent clinical studies showing similar success rates comparable to
      open procedures. These improved success rates are likely due to a better
      understanding of the pathoanatomy of shoulder instability and addressing all
      injured structures including labral tears and capsular injury and stretching. I
      present a new arthroscopic technique for shoulder stabilization that makes use of
      already known techniques by sequentially repairing the labral tear and performing
      a capsular shift through multiple, separate pleated plications through a single
      working portal. This technique allows for an anatomic labral repair with a
      capsular shift as large as desired by performing as many additional tucks of
      capsule for plication as needed, comparable to open techniques with less
      surrounding tissue trauma. This technique is actually easier than more
      traditional arthroscopic methods, and the multiple pleats may provide a load
      sharing effect dispersed through each pleat, which may decrease the risk of load
      failure.

PMID- 15944645
TI  - Management of bony deficiency in revision anterior cruciate ligament
      reconstruction using allograft bone dowels: surgical technique.
AB  - Revision anterior cruciate ligament (ACL) reconstruction surgery has become
      increasingly common over the past decade and its popularity is likely to rise
      further as the number of primary ACL reconstructions increases each year. More
      than 75% of all cases of failed ACL reconstruction are the result of technical
      error and, of these, more than 70% are attributed specifically to malpositioned
      tunnels. Management of tunnel malposition in revision surgery often requires
      innovative approaches for dealing with the resultant bony defects. In addition,
      tunnel osteolysis may create bone loss that interferes with desired tunnel
      placement. A number of options have been described for handling these bony
      deficiencies, many of which are technically difficult and time consuming. We
      describe a novel technique to address bony defects during revision ACL
      reconstruction using freeze-dried allograft bone dowels. These allografts are
      readily available and can be used easily to fill deficiencies resulting from
      previous tunnels or osteolysis. The grafts provide sufficient structural support
      for redrilling of new tunnels through or next to the bony plug, allowing
      uncompromised tunnel placement.

PMID- 15944646
TI  - New meniscus repair by an all-inside knot suture technique.
AB  - The indications for the all-inside knot suture technique include tears in the red
      red zone or red-white zone in the meniscus, and a horizontal tear, a vertical
      tear, and a peripheral tear. First, find an appropriate place for a suture
      insertion site with a Kateran needle or a spinal needle. Make sure it exits
      beyond the tear in the meniscus. Once the insertion site is chosen, a suture is
      passed into and through the joint. The suture is slowly pulled back. You should
      be able to feel the tip of the suture come out of the joint capsule. If you want
      to make a vertical suture to suture the tear, move the suture vertically apex.
      Then insert the suture back into the joint through the capsule. Make sure the
      suture stays inside the joint. Find and grab the suture with a punch inserted
      from the clear cannula. Pull the suture out of the joint through the clear
      cannula with the punch. Tighten the knot with a knot pusher. Then confirm the
      stability of the sutured site with the probe. Our all-inside knot suture
      technique can be performed arthroscopically, allowing reliable repair of the torn
      meniscus.

PMID- 15944647
TI  - Reverse achilles tendon allograft technique for anterior cruciate ligament
      reconstruction.
AB  - Because of the increasing popularity of allograft anterior cruciate ligament
      (ACL) reconstructions, the technical difficulties with posterior bone loss in
      revision ACL surgery, and the limited supply of bone-patellar tendon-bone donor
      grafts, we have developed a technique using a reversed Achilles tendon allograft
      to reconstruct the ACL-deficient knee. This technique allows for bony tibial
      fixation with an interference screw by rotating the graft 180 degrees and
      optimizing soft-tissue fixation at the femur with an EndoButton CL (Smith &
      Nephew, Andover, MA). Short-term follow-up (average, 26.4 weeks) of 10 patients
      undergoing the reversed Achilles technique has shown excellent results, with
      Lysholm scores between 91 and 100 and 84 and 90 in 8 of 10 and 2 of 10 patients,
      respectively. Objective stability assessments, including the Lachman test,
      anterior drawer, and pivot-shift tests, were also encouraging. Reverse Achilles
      tendon allografts can be excellent alternatives for ACL reconstruction when bone
      patellar tendon-bone grafts are not indicated.

PMID- 15944648
TI  - Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and
      blood volume in normal circulation.
AB  - To investigate the vasoconstrictor effect of 5-hydroxytryptamine (5-HT1B/1D)
      receptor agonists for migraine treatment, changes in cerebral blood flow (CBF)
      and blood volume induced by rizatriptan were assessed by positron emission
      tomography (PET). Eleven healthy volunteers underwent PET studies before and
      after rizatriptan administration. Dynamic PET data were acquired after bolus
      injection of H2(15)O to analyze CBF and arterial-to-capillary blood volume (V0)
      images using the three-weighted integral method. After a baseline scan, three
      further acquisitions were performed at 40 to 50, 60 and 70 to 80 mins after drug
      administration. Global and regional differences in CBF and V0 between conditions
      were compared using absolute values in the whole brain and cortical regions, as
      well as statistical parametric mapping (SPM) analysis. The global and regional
      values for CBF and V0 decreased significantly after rizatriptan administration
      compared with the baseline condition. However, both values recovered to baseline
      within 80 mins after treatment. The maximal reduction in global CBF and V0 was
      approximately 13% of baseline value. The greatest decrease in CBF was observed
      approximately 60 mins after drug administration, whereas the maximal reduction in
      V0 was observed approximately 5 mins earlier. Statistical parametric mapping did
      not highlight any regional differences between conditions. Thus, in brain
      circulation, rizatriptan caused significant CBF and V0 decreases, which are
      consistent with the vasoconstrictor effect of triptans on the large cerebral
      arteries. The gradual recovery in the late phase from the maximal CBF and V0
      decrease suggests that rizatriptan does not affect the cerebral autoregulatory
      response in small arteries induced by CBF reduction.

PMID- 15944649
TI  - Kinetic modeling of amyloid binding in humans using PET imaging and Pittsburgh
      Compound-B.
AB  - A valid quantitative imaging method for the measurement of amyloid deposition in
      humans could improve Alzheimer's disease (AD) diagnosis and antiamyloid therapy
      assessment. Our group developed Pittsburgh Compound-B (PIB), an amyloid-binding
      radiotracer, for positron emission tomography (PET). The current study was aimed
      to further validate PIB PET through quantitative imaging (arterial input) and
      inclusion of subjects with mild cognitive impairment (MCI). Pittsburgh Compound-B
      studies were performed in five AD, five MCI, and five control subjects and five
      subjects were retested within 20 days. Magnetic resonance images were acquired
      for partial volume correction and region-of-interest definition (e.g., posterior
      cingulate: PCG; cerebellum: CER). Data were analyzed using compartmental and
      graphical approaches. Regional distribution volume (DV) values were normalized to
      the reference region (CER) to yield DV ratios (DVRs). Good agreement was observed
      between compartmental and Logan DVR values (e.g., PCG: r=0.89, slope=0.91); the
      Logan results were less variable. Nonspecific PIB retention was similar across
      subjects (n=15, Logan CER DV: 3.63+/-0.48). Greater retention was observed in AD
      cortical areas, relative to controls (P<0.05). The PIB retention in MCI subjects
      appeared either 'AD-like' or 'control-like'. The mean test/retest variation was
      approximately 6% in primary areas-of-interest. The Logan analysis was the method
      of-choice for the PIB PET data as it proved stable, valid, and promising for
      future larger studies and voxel-based statistical analyses. This study also
      showed that it is feasible to perform quantitative PIB PET imaging studies that
      are needed to validate simpler methods for routine use across the AD disease
      spectrum.

PMID- 15944650
TI  - Nondisease genetic testing: reporting of muscle SNPs shows effects on self
      concept and health orientation scales.
AB  - The purpose of this study was to assess the impact of genetic self-knowledge
      (nondisease genotype information) on individual self-concept and Health
      Orientation Scale (HOS). Adult volunteers (n=257) were recruited from an ongoing
      genetic association study identifying muscle quantitative trait loci (QTLs).
      Participants completed psychosocial assessments before and after 12 weeks of
      resistance training of the nondominant arm. At study exit, a genetic counselor
      informed participants of genetic test results on three to four genes that have an
      association with muscle-related traits, and counseled subjects on the potential
      significance of these findings. The second psychosocial assessment was performed
      immediately following this counseling session. The Tennessee Self-Concept Scale
      v.2 (TSCS:2) and the HOS showed female subjects to have a significantly greater
      positive change between first and second assessments, relative to male subjects.
      Most self-concept subscales improved significantly, when 'neutral' genotypes (no
      anticipated beneficial or deleterious impact) were reported, compared to positive
      genotypes. TSCS:2 subscales showing improvement included: total (P=0.013);
      physical (P=0.004); satisfaction (P=0.019); and behavioral (P=0.047). HOS
      subscales showing improvement included health image concern (P=0.006); and health
      expectations (P=0.047). In conclusion, these results suggest that genetic self
      knowledge affects self-concept, consistent with the 'attribution' theory.
      Individuals who received neutral genetic information attributed positive changes
      from the exercise program to their own abilities, while those who received
      positive information were more likely to attribute positive changes to their
      genetics. This study is limited by the ability to determine the direction of the
      impact of nondisease genetic information presented to participants.

PMID- 15944651
TI  - Estrogen receptor beta gene variants are associated with increased risk of
      Alzheimer's disease in women.
AB  - We investigated the association of five intronic single-nucleotide polymorphism
      (SNP) at the estrogen receptor beta (ESR2) gene locus and the susceptibility of
      developing Alzheimer's disease (AD) in 387 subjects with clinically diagnosed
      probable AD and 467 cognitively normal individuals derived from eastern Finland.
      According to our results, variation in the ESR2 gene is associated with an
      increased risk of AD in women, whereas it does not contribute to the disease
      susceptibility in men. More specifically, in women, the allele T and the genotype
      T/T of two of the studied ESR2 gene SNPs (SNP2 and SNP3) were more frequent in AD
      women than in cognitively normal control women (P=0.012 and P=0.016,
      respectively). The ESR2 SNP2 T/T genotype and the SNP3 T/T genotype were
      associated with a significant, nearly two-fold increase in the risk of AD in
      women (OR=1.87, 95% CI=1.21-2.90), and remained significant after adjustment with
      the APOE genotype and age (OR=1.63, 95% CI, 1.00-1.68). The combined effect of
      the ESR2 SNP2 T/T or SNP3 T/T genotype and female gender increases the risk of
      the disease (OR=3.2, 95% CI=1.3-7.7). Consistent with these results, also the
      frequency of the haplotype containing the two above ESR2 gene risk alleles was
      elevated in AD women (P=0.027, OR=1.3, 95% CI=1.02-1.65). Results show that
      variation in ESR2 gene may be linked with increased AD susceptibility and
      furthermore, this association is gender specific.

PMID- 15944652
TI  - Kyoto--the sequel.

PMID- 15944653
TI  - All or nothing at Fermilab.

PMID- 15944654
TI  - Talent worth nurturing.

PMID- 15944656
TI  - One in three scientists confesses to having sinned.

PMID- 15944657
TI  - Chemistry society goes head to head with NIH in fight over public database.

PMID- 15944658
TI  - Europe halts decisions on stem-cell patents.

PMID- 15944659
TI  - Blue Brain boots up to mixed response.

PMID- 15944660
TI  - Snapshot: sunlight on an icy martian crater.

PMID- 15944661
TI  - Soap opera reaps prize for its clean message.

PMID- 15944662
TI  - Pall hangs over desert's future as alien weeds fuel wildfires.

PMID- 15944664
TI  - Evolutionist row makes museum ditch donation.

PMID- 15944667
TI  - Fermilab: high-risk physics.

PMID- 15944668
TI  - Space physiology: lie back and think of science.

PMID- 15944669
TI  - Climate change: that sinking feeling.

PMID- 15944670
TI  - Touched by an angel.

PMID- 15944673
TI  - A boycott could do good in Israel, as in South Africa.

PMID- 15944674
TI  - Academic boycott would damage chances for peace.

PMID- 15944675
TI  - Veracity of raw images can also come into question.

PMID- 15944676
TI  - Controls on exports will defend security, without harming labs.

PMID- 15944677
TI  - Scientists behaving badly.

PMID- 15944681
TI  - Physics, complexity and causality.

PMID- 15944682
TI  - Cancer genomics: small RNAs with big impacts.

PMID- 15944683
TI  - Organic chemistry: fast reactions 'on water'.

PMID- 15944684
TI  - Structural biology: prying into prions.

PMID- 15944686
TI  - Planetary science: shades of Titan.

PMID- 15944687
TI  - Plant-fungal associations: cue for the branching connection.

PMID- 15944688
TI  - Computational science: can get satisfaction.

PMID- 15944689
TI  - Cancer: inflammation by remote control.

PMID- 15944691
TI  - Seismology: earthquake risk on the Sunda trench.
AB  - On 28 March 2005 the Sunda megathrust in Indonesia ruptured again, producing
      another great earthquake three months after the previous one. The rupture was
      contiguous with that of the December 2004 Sumatra-Andaman earthquake, and is
      likely to have been sparked by local stress, although the triggering stresses at
      its hypocentre were very small - of the order of just 0.1 bar. Calculations show
      that stresses imposed by the second rupture have brought closer to failure the
      megathrust immediately to the south, under the Batu and Mentawai islands, and
      have expanded the area of increased stress on the Sumatra fault.
      Palaeoseismologic studies show that the Mentawai segment of the Sunda megathrust
      is well advanced in its seismic cycle and is therefore a good candidate for
      triggered failure.

PMID- 15944690
TI  - Brevetoxicosis: red tides and marine mammal mortalities.
AB  - Potent marine neurotoxins known as brevetoxins are produced by the 'red tide'
      dinoflagellate Karenia brevis. They kill large numbers of fish and cause illness
      in humans who ingest toxic filter-feeding shellfish or inhale toxic aerosols. The
      toxins are also suspected of having been involved in events in which many
      manatees and dolphins died, but this has usually not been verified owing to
      limited confirmation of toxin exposure, unexplained intoxication mechanisms and
      complicating pathologies. Here we show that fish and seagrass can accumulate high
      concentrations of brevetoxins and that these have acted as toxin vectors during
      recent deaths of dolphins and manatees, respectively. Our results challenge
      claims that the deleterious effects of a brevetoxin on fish (ichthyotoxicity)
      preclude its accumulation in live fish, and they reveal a new vector mechanism
      for brevetoxin spread through food webs that poses a threat to upper trophic
      levels.

PMID- 15944692
TI  - Plant biochemistry: anthocyanin biosynthesis in roses.
AB  - Anthocyanin is the principal pigment in flowers, conferring intense red-to-blue
      cyanic colours on petals and helping to attract pollinators. Its biosynthesis
      involves glycosylation steps that are important for the stability of the pigment
      and for its aqueous solubility in vacuoles. Here we describe anthocyanin
      biosynthesis in roses (Rosa hybrida), which is unlike the pathway used in other
      flowers in that it relies on a single enzyme to achieve glycosylation at two
      different positions on the precursor molecule. Phylogenetic analysis also
      indicates that this previously unknown glucosyltransferase enzyme may be unique
      to roses, with glycosylation having apparently evolved into a single stabilizing
      step in other plants.

PMID- 15944693
TI  - Rigorous location of phase transitions in hard optimization problems.
AB  - It is widely believed that for many optimization problems, no algorithm is
      substantially more efficient than exhaustive search. This means that finding
      optimal solutions for many practical problems is completely beyond any current or
      projected computational capacity. To understand the origin of this extreme
      'hardness', computer scientists, mathematicians and physicists have been
      investigating for two decades a connection between computational complexity and
      phase transitions in random instances of constraint satisfaction problems. Here
      we present a mathematically rigorous method for locating such phase transitions.
      Our method works by analysing the distribution of distances between pairs of
      solutions as constraints are added. By identifying critical behaviour in the
      evolution of this distribution, we can pinpoint the threshold location for a
      number of problems, including the two most-studied ones: random k-SAT and random
      graph colouring. Our results prove that the heuristic predictions of statistical
      physics in this context are essentially correct. Moreover, we establish that
      random instances of constraint satisfaction problems have solutions well beyond
      the reach of any analysed algorithm.

PMID- 15944694
TI  - Structural insights into a yeast prion illuminate nucleation and strain
      diversity.
AB  - Self-perpetuating changes in the conformations of amyloidogenic proteins play
      vital roles in normal biology and disease. Despite intense research, the
      architecture and conformational conversion of amyloids remain poorly understood.
      Amyloid conformers of Sup35 are the molecular embodiment of the yeast prion known
      as [PSI], which produces heritable changes in phenotype through self-perpetuating
      changes in protein folding. Here we determine the nature of Sup35's cooperatively
      folded amyloid core, and use this information to investigate central questions in
      prion biology. Specific segments of the amyloid core form intermolecular contacts
      in a 'Head-to-Head', 'Tail-to-Tail' fashion, but the 'Central Core' is
      sequestered through intramolecular contacts. The Head acquires productive
      interactions first, and these nucleate assembly. Variations in the length of the
      amyloid core and the nature of intermolecular interfaces form the structural
      basis of distinct prion 'strains', which produce variant phenotypes in vivo.
      These findings resolve several problems in yeast prion biology and have broad
      implications for other amyloids.

PMID- 15944695
TI  - Structure of the cross-beta spine of amyloid-like fibrils.
AB  - Numerous soluble proteins convert to insoluble amyloid-like fibrils that have
      common properties. Amyloid fibrils are associated with fatal diseases such as
      Alzheimer's, and amyloid-like fibrils can be formed in vitro. For the yeast
      protein Sup35, conversion to amyloid-like fibrils is associated with a
      transmissible infection akin to that caused by mammalian prions. A seven-residue
      peptide segment from Sup35 forms amyloid-like fibrils and closely related
      microcrystals, from which we have determined the atomic structure of the cross
      beta spine. It is a double beta-sheet, with each sheet formed from parallel
      segments stacked in register. Side chains protruding from the two sheets form a
      dry, tightly self-complementing steric zipper, bonding the sheets. Within each
      sheet, every segment is bound to its two neighbouring segments through stacks of
      both backbone and side-chain hydrogen bonds. The structure illuminates the
      stability of amyloid fibrils, their self-seeding characteristic and their
      tendency to form polymorphic structures.

PMID- 15944698
TI  - Discovery of an aurora on Mars.
AB  - In the high-latitude regions of Earth, aurorae are the often-spectacular visual
      manifestation of the interaction between electrically charged particles
      (electrons, protons or ions) with the neutral upper atmosphere, as they
      precipitate along magnetic field lines. More generally, auroral emissions in
      planetary atmospheres "are those that result from the impact of particles other
      than photoelectrons" (ref. 1). Auroral activity has been found on all four giant
      planets possessing a magnetic field (Jupiter, Saturn, Uranus and Neptune), as
      well as on Venus, which has no magnetic field. On the nightside of Venus, atomic
      O emissions at 130.4 nm and 135.6 nm appear in bright patches of varying sizes
      and intensities, which are believed to be produced by electrons with energy <300
      eV (ref. 7). Here we report the discovery of an aurora in the martian atmosphere,
      using the ultraviolet spectrometer SPICAM on board Mars Express. It corresponds
      to a distinct type of aurora not seen before in the Solar System: it is unlike
      aurorae at Earth and the giant planets, which lie at the foot of the intrinsic
      magnetic field lines near the magnetic poles, and unlike venusian auroras, which
      are diffuse, sometimes spreading over the entire disk. Instead, the martian
      aurora is a highly concentrated and localized emission controlled by magnetic
      field anomalies in the martian crust.

PMID- 15944696
TI  - The structure of the myosin VI motor reveals the mechanism of directionality
      reversal.
AB  - Here we solve a 2.4-A structure of a truncated version of the reverse-direction
      myosin motor, myosin VI, that contains the motor domain and binding sites for two
      calmodulin molecules. The structure reveals only minor differences in the motor
      domain from that in plus-end directed myosins, with the exception of two unique
      inserts. The first is near the nucleotide-binding pocket and alters the rates of
      nucleotide association and dissociation. The second unique insert forms an
      integral part of the myosin VI converter domain along with a calmodulin bound to
      a novel target motif within the insert. This serves to redirect the effective
      'lever arm' of myosin VI, which includes a second calmodulin bound to an 'IQ
      motif', towards the pointed (minus) end of the actin filament. This repositioning
      largely accounts for the reverse directionality of this class of myosin motors.
      We propose a model incorporating a kinesin-like uncoupling/docking mechanism to
      provide a full explanation of the movements of myosin VI.

PMID- 15944697
TI  - Release of volatiles from a possible cryovolcano from near-infrared imaging of
      Titan.
AB  - Titan is the only satellite in our Solar System with a dense atmosphere. The
      surface pressure is 1.5 bar (ref. 1) and, similar to the Earth, N2 is the main
      component of the atmosphere. Methane is the second most important component, but
      it is photodissociated on a timescale of 10(7) years (ref. 3). This short
      timescale has led to the suggestion that Titan may possess a surface or
      subsurface reservoir of hydrocarbons to replenish the atmosphere. Here we report
      near-infrared images of Titan obtained on 26 October 2004 by the Cassini
      spacecraft. The images show that a widespread methane ocean does not exist;
      subtle albedo variations instead suggest topographical variations, as would be
      expected for a more solid (perhaps icy) surface. We also find a circular
      structure approximately 30 km in diameter that does not resemble any features
      seen on other icy satellites. We propose that the structure is a dome formed by
      upwelling icy plumes that release methane into Titan's atmosphere.

PMID- 15944699
TI  - A thermally self-sustained micro solid-oxide fuel-cell stack with high power
      density.
AB  - High energy efficiency and energy density, together with rapid refuelling
      capability, render fuel cells highly attractive for portable power generation.
      Accordingly, polymer-electrolyte direct-methanol fuel cells are of increasing
      interest as possible alternatives to Li ion batteries. However, such fuel cells
      face several design challenges and cannot operate with hydrocarbon fuels of
      higher energy density. Solid-oxide fuel cells (SOFCs) enable direct use of higher
      hydrocarbons, but have not been seriously considered for portable applications
      because of thermal management difficulties at small scales, slow start-up and
      poor thermal cyclability. Here we demonstrate a thermally self-sustaining micro
      SOFC stack with high power output and rapid start-up by using single chamber
      operation on propane fuel. The catalytic oxidation reactions supply sufficient
      thermal energy to maintain the fuel cells at 500-600 degrees C. A power output of
      approximately 350 mW (at 1.0 V) was obtained from a device with a total cathode
      area of only 1.42 cm2.

PMID- 15944700
TI  - Lightning-induced intensification of the ionospheric sporadic E layer.
AB  - A connection between thunderstorms and the ionosphere has been hypothesized since
      the mid-1920s. Several mechanisms have been proposed to explain this connection,
      and evidence from modelling as well as various types of measurements demonstrate
      that lightning can interact with the lower ionosphere. It has been proposed, on
      the basis of a few observed events, that the ionospheric 'sporadic E' layer-
      transient, localized patches of relatively high electron density in the mid
      ionosphere E layer, which significantly affect radio-wave propagation--can be
      modulated by thunderstorms, but a more formal statistical analysis is still
      needed. Here we identify a statistically significant intensification and descent
      in altitude of the mid-latitude sporadic E layer directly above thunderstorms.
      Because no ionospheric response to low-pressure systems without lightning is
      detected, we conclude that this localized intensification of the sporadic E layer
      can be attributed to lightning. We suggest that the co-location of lightning and
      ionospheric enhancement can be explained by either vertically propagating gravity
      waves that transfer energy from the site of lightning into the ionosphere, or
      vertical electrical discharge, or by a combination of these two mechanisms.

PMID- 15944701
TI  - Geomagnetic dipole strength and reversal rate over the past two million years.
AB  - Independent records of relative magnetic palaeointensity from sediment cores in
      different areas of the world can be stacked together to extract the evolution of
      the geomagnetic dipole moment and thus provide information regarding the
      processes governing the geodynamo. So far, this procedure has been limited to the
      past 800,000 years (800 kyr; ref. 3), which does not include any geomagnetic
      reversals. Here we present a composite curve that shows the evolution of the
      dipole moment during the past two million years. This reconstruction is in good
      agreement with the absolute dipole moments derived from volcanic lavas, which
      were used for calibration. We show that, at least during this period, the time
      averaged field was higher during periods without reversals but the amplitude of
      the short-term oscillations remained the same. As a consequence, few intervals of
      very low intensity, and thus fewer instabilities, are expected during periods
      with a strong average dipole moment, whereas more excursions and reversals are
      expected during periods of weak field intensity. We also observe that the axial
      dipole begins to decay 60-80 kyr before reversals, but rebuilds itself in the
      opposite direction in only a few thousand years.

PMID- 15944702
TI  - Effects of species and functional group loss on island ecosystem properties.
AB  - Considerable recent attention has focused on predicting how the losses of species
      and functional groups influence ecosystem properties, but the extent to which
      these effects vary among ecosystems remains poorly understood. Island systems
      have considerable scope for studying how biotic and abiotic factors influence
      processes in different ecosystems, because they enable the simultaneous study of
      large numbers of independent replicate systems at ecologically meaningful spatial
      scales. We studied a group of 30 islands in northern Sweden, for which island
      size determined disturbance history, and therefore vegetation successional stage
      and biotic and abiotic ecosystem properties. On each island we conducted a seven
      year study that involved experimental removals of combinations of both plant
      functional groups and plant species. We show that although losses of functional
      groups and species often impaired key ecosystem processes, these effects were
      highly context-dependent and strongly influenced by island size. Our study
      provides evidence that the consequences of biotic loss for ecosystem functioning
      vary greatly among ecosystems and depend on the specific abiotic and biotic
      attributes of the system.

PMID- 15944703
TI  - Average remaining lifetimes can increase as human populations age.
AB  - Increases in median ages, the most commonly used measure of population ageing,
      are rapid in today's wealthier countries, and population ageing is widely
      considered to be a significant challenge to the well-being of citizens there.
      Conventional measures of age count years since birth; however, as lives lengthen,
      we need to think of age also in terms of years left until death or in proportion
      to the expanding lifespan. Here we propose a new measure of ageing: the median
      age of the population standardized for expected remaining years of life. We show,
      using historical data and forecasts for Germany, Japan and the United States,
      that although these populations will be growing older, as measured by their
      median ages, they will probably experience periods in which they grow younger, as
      measured by their standardized median ages. Furthermore, we provide forecasts for
      these countries of the old-age dependency ratio rescaled for increases in life
      expectancy at birth. These ratios are forecasted to change much less than their
      unscaled counterparts, and also exhibit periods when the population is
      effectively growing younger.

PMID- 15944704
TI  - Uncovering the overlapping community structure of complex networks in nature and
      society.
AB  - Many complex systems in nature and society can be described in terms of networks
      capturing the intricate web of connections among the units they are made of. A
      key question is how to interpret the global organization of such networks as the
      coexistence of their structural subunits (communities) associated with more
      highly interconnected parts. Identifying these a priori unknown building blocks
      (such as functionally related proteins, industrial sectors and groups of people)
      is crucial to the understanding of the structural and functional properties of
      networks. The existing deterministic methods used for large networks find
      separated communities, whereas most of the actual networks are made of highly
      overlapping cohesive groups of nodes. Here we introduce an approach to analysing
      the main statistical features of the interwoven sets of overlapping communities
      that makes a step towards uncovering the modular structure of complex systems.
      After defining a set of new characteristic quantities for the statistics of
      communities, we apply an efficient technique for exploring overlapping
      communities on a large scale. We find that overlaps are significant, and the
      distributions we introduce reveal universal features of networks. Our studies of
      collaboration, word-association and protein interaction graphs show that the web
      of communities has non-trivial correlations and specific scaling properties.

PMID- 15944705
TI  - Nitrogen transfer in the arbuscular mycorrhizal symbiosis.
AB  - Most land plants are symbiotic with arbuscular mycorrhizal fungi (AMF), which
      take up mineral nutrients from the soil and exchange them with plants for
      photosynthetically fixed carbon. This exchange is a significant factor in global
      nutrient cycles as well as in the ecology, evolution and physiology of plants.
      Despite its importance as a nutrient, very little is known about how AMF take up
      nitrogen and transfer it to their host plants. Here we report the results of
      stable isotope labelling experiments showing that inorganic nitrogen taken up by
      the fungus outside the roots is incorporated into amino acids, translocated from
      the extraradical to the intraradical mycelium as arginine, but transferred to the
      plant without carbon. Consistent with this mechanism, the genes of primary
      nitrogen assimilation are preferentially expressed in the extraradical tissues,
      whereas genes associated with arginine breakdown are more highly expressed in the
      intraradical mycelium. Strong changes in the expression of these genes in
      response to nitrogen availability and form also support the operation of this
      novel metabolic pathway in the arbuscular mycorrhizal symbiosis.

PMID- 15944706
TI  - Plant sesquiterpenes induce hyphal branching in arbuscular mycorrhizal fungi.
AB  - Arbuscular mycorrhizal (AM) fungi form mutualistic, symbiotic associations with
      the roots of more than 80% of land plants. The fungi are incapable of completing
      their life cycle in the absence of a host root. Their spores can germinate and
      grow in the absence of a host, but their hyphal growth is very limited. Little is
      known about the molecular mechanisms that govern signalling and recognition
      between AM fungi and their host plants. In one of the first stages of host
      recognition, the hyphae of AM fungi show extensive branching in the vicinity of
      host roots before formation of the appressorium, the structure used to penetrate
      the plant root. Host roots are known to release signalling molecules that trigger
      hyphal branching, but these branching factors have not been isolated. Here we
      have isolated a branching factor from the root exudates of Lotus japonicus and
      used spectroscopic analysis and chemical synthesis to identify it as a
      strigolactone, 5-deoxy-strigol. Strigolactones are a group of sesquiterpene
      lactones, previously isolated as seed-germination stimulants for the parasitic
      weeds Striga and Orobanche. The natural strigolactones 5-deoxy-strigol,
      sorgolactone and strigol, and a synthetic analogue, GR24, induced extensive
      hyphal branching in germinating spores of the AM fungus Gigaspora margarita at
      very low concentrations.

PMID- 15944707
TI  - A microRNA polycistron as a potential human oncogene.
AB  - To date, more than 200 microRNAs have been described in humans; however, the
      precise functions of these regulatory, non-coding RNAs remains largely obscure.
      One cluster of microRNAs, the mir-17-92 polycistron, is located in a region of
      DNA that is amplified in human B-cell lymphomas. Here we compared B-cell lymphoma
      samples and cell lines to normal tissues, and found that the levels of the
      primary or mature microRNAs derived from the mir-17-92 locus are often
      substantially increased in these cancers. Enforced expression of the mir-17-92
      cluster acted with c-myc expression to accelerate tumour development in a mouse B
      cell lymphoma model. Tumours derived from haematopoietic stem cells expressing a
      subset of the mir-17-92 cluster and c-myc could be distinguished by an absence of
      apoptosis that was otherwise prevalent in c-myc-induced lymphomas. Together,
      these studies indicate that non-coding RNAs, specifically microRNAs, can modulate
      tumour formation, and implicate the mir-17-92 cluster as a potential human
      oncogene.

PMID- 15944708
TI  - MicroRNA expression profiles classify human cancers.
AB  - Recent work has revealed the existence of a class of small non-coding RNA
      species, known as microRNAs (miRNAs), which have critical functions across
      various biological processes. Here we use a new, bead-based flow cytometric miRNA
      expression profiling method to present a systematic expression analysis of 217
      mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA
      profiles are surprisingly informative, reflecting the developmental lineage and
      differentiation state of the tumours. We observe a general downregulation of
      miRNAs in tumours compared with normal tissues. Furthermore, we were able to
      successfully classify poorly differentiated tumours using miRNA expression
      profiles, whereas messenger RNA profiles were highly inaccurate when applied to
      the same samples. These findings highlight the potential of miRNA profiling in
      cancer diagnosis.

PMID- 15944709
TI  - c-Myc-regulated microRNAs modulate E2F1 expression.
AB  - MicroRNAs (miRNAs) are 21-23 nucleotide RNA molecules that regulate the stability
      or translational efficiency of target messenger RNAs. miRNAs have diverse
      functions, including the regulation of cellular differentiation, proliferation
      and apoptosis. Although strict tissue- and developmental-stage-specific
      expression is critical for appropriate miRNA function, mammalian transcription
      factors that regulate miRNAs have not yet been identified. The proto-oncogene c
      MYC encodes a transcription factor that regulates cell proliferation, growth and
      apoptosis. Dysregulated expression or function of c-Myc is one of the most common
      abnormalities in human malignancy. Here we show that c-Myc activates expression
      of a cluster of six miRNAs on human chromosome 13. Chromatin immunoprecipation
      experiments show that c-Myc binds directly to this locus. The transcription
      factor E2F1 is an additional target of c-Myc that promotes cell cycle
      progression. We find that expression of E2F1 is negatively regulated by two
      miRNAs in this cluster, miR-17-5p and miR-20a. These findings expand the known
      classes of transcripts within the c-Myc target gene network, and reveal a
      mechanism through which c-Myc simultaneously activates E2F1 transcription and
      limits its translation, allowing a tightly controlled proliferative signal.

PMID- 15944711
TI  - French lessons.

PMID- 15944710
TI  - Correlation of structural elements and infectivity of the HET-s prion.
AB  - Prions are believed to be infectious, self-propagating polymers of otherwise
      soluble, host-encoded proteins. This concept is now strongly supported by the
      recent findings that amyloid fibrils of recombinant prion proteins from yeast,
      Podospora anserina and mammals can induce prion phenotypes in the corresponding
      hosts. However, the structural basis of prion infectivity remains largely elusive
      because acquisition of atomic resolution structural properties of amyloid fibrils
      represents a largely unsolved technical challenge. HET-s, the prion protein of P.
      anserina, contains a carboxy-terminal prion domain comprising residues 218-289.
      Amyloid fibrils of HET-s(218-289) are necessary and sufficient for the induction
      and propagation of prion infectivity. Here, we have used fluorescence studies,
      quenched hydrogen exchange NMR and solid-state NMR to determine the sequence
      specific positions of amyloid fibril secondary structure elements of HET-s(218
      289). This approach revealed four beta-strands constituted by two pseudo-repeat
      sequences, each forming a beta-strand-turn-beta-strand motif. By using a
      structure-based mutagenesis approach, we show that this conformation is the
      functional and infectious entity of the HET-s prion. These results correlate
      distinct structural elements with prion infectivity.

PMID- 15944712
TI  - Getting schooled.

PMID- 15944714
TI  - Stem cell division is regulated by the microRNA pathway.
AB  - One of the key characteristics of stem cells is their capacity to divide for long
      periods of time in an environment where most of the cells are quiescent.
      Therefore, a critical question in stem cell biology is how stem cells escape cell
      division stop signals. Here, we report the necessity of the microRNA (miRNA)
      pathway for proper control of germline stem cell (GSC) division in Drosophila
      melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded
      RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate
      of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but
      are defective in cell cycle control. On the basis of cell cycle markers and
      genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to
      S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo,
      suggesting that miRNAs are required for stem cells to bypass the normal G1/S
      checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem
      cells insensitive to environmental signals that normally stop the cell cycle at
      the G1/S transition.

PMID- 15944715
TI  - Triplet-singlet spin relaxation via nuclei in a double quantum dot.
AB  - The spin of a confined electron, when oriented originally in some direction, will
      lose memory of that orientation after some time. Physical mechanisms leading to
      this relaxation of spin memory typically involve either coupling of the electron
      spin to its orbital motion or to nuclear spins. Relaxation of confined electron
      spin has been previously measured only for Zeeman or exchange split spin states,
      where spin-orbit effects dominate relaxation; spin flips due to nuclei have been
      observed in optical spectroscopy studies. Using an isolated GaAs double quantum
      dot defined by electrostatic gates and direct time domain measurements, we
      investigate in detail spin relaxation for arbitrary splitting of spin states.
      Here we show that electron spin flips are dominated by nuclear interactions and
      are slowed by several orders of magnitude when a magnetic field of a few
      millitesla is applied. These results have significant implications for spin-based
      information processing.

PMID- 15944716
TI  - Astronomical pacing of late Palaeocene to early Eocene global warming events.
AB  - At the boundary between the Palaeocene and Eocene epochs, about 55 million years
      ago, the Earth experienced a strong global warming event, the Palaeocene-Eocene
      thermal maximum. The leading hypothesis to explain the extreme greenhouse
      conditions prevalent during this period is the dissociation of 1,400 to 2,800
      gigatonnes of methane from ocean clathrates, resulting in a large negative carbon
      isotope excursion and severe carbonate dissolution in marine sediments. Possible
      triggering mechanisms for this event include crossing a threshold temperature as
      the Earth warmed gradually, comet impact, explosive volcanism or ocean current
      reorganization and erosion at continental slopes, whereas orbital forcing has
      been excluded. Here we report a distinct carbonate-poor red clay layer in deep
      sea cores from Walvis ridge, which we term the Elmo horizon. Using orbital
      tuning, we estimate deposition of the Elmo horizon at about 2 million years after
      the Palaeocene-Eocene thermal maximum. The Elmo horizon has similar geochemical
      and biotic characteristics as the Palaeocene-Eocene thermal maximum, but of
      smaller magnitude. It is coincident with carbon isotope depletion events in other
      ocean basins, suggesting that it represents a second global thermal maximum. We
      show that both events correspond to maxima in the approximately 405-kyr and
      approximately 100-kyr eccentricity cycles that post-date prolonged minima in the
      2.25-Myr eccentricity cycle, implying that they are indeed astronomically paced.

PMID- 15944717
TI  - Mutational status of IgV(H) genes in B-cell chronic lymphocytic leukemia and
      prognosis: percent mutations or antigen-driven selection?

PMID- 15944718
TI  - Is there a role for postremission therapy in older adults with acute myelogenous
      leukemia (AML)?

PMID- 15944719
TI  - FOXP1, a gene highly expressed in a subset of diffuse large B-cell lymphoma, is
      recurrently targeted by genomic aberrations.
AB  - The transcription factor Forkhead box protein P1 (FOXP1) is highly expressed in a
      proportion of diffuse large B-cell lymphoma (DLBCL). In this report, we provide
      cytogenetic and fluorescence in situ hybridization (FISH) data showing that FOXP1
      (3p13) is recurrently targeted by chromosome translocations. The genomic
      rearrangement of FOXP1 was identified by FISH in three cases with a
      t(3;14)(p13;q32) involving the immunoglobulin heavy chain (IGH) locus, and in one
      case with a variant t(2;3) affecting sequences at 2q36. These aberrations were
      associated with strong expression of FOXP1 protein in tumor cells, as
      demonstrated by immunohistochemistry (IHC). The cases with t(3p13) were diagnosed
      as DLBCL ( x 1), gastric MALT lymphoma ( x 1) and B-cell non-Hodgkin's lymphoma,
      not otherwise specified ( x 2). Further IHC and FISH studies performed on 98
      cases of DLBCL and 93 cases of extranodal marginal zone lymphoma showed a high
      expression of FOXP1 in approximately 13 and 12% of cases, respectively. None of
      these cases showed, however, FOXP1 rearrangements by FISH. However, over
      representation of the FOXP1 locus found in one additional case of DLBCL may
      represent another potential mechanism underlying an increased expression of this
      gene.

PMID- 15944720
TI  - C-reactive protein, atherosclerosis and kidney function in hypertensive patients.
AB  - Previous studies have shown a relationship between coronary or carotid
      atherosclerosis and C-reactive protein (CRP) concentrations. In the present
      investigation, we evaluated the relationship between high-sensitivity CRP (hsCRP)
      concentrations and the presence of atherosclerotic lesions in the renal arteries
      and/or abdominal aorta. In 95 hypertensive patients who underwent intra-arterial
      DSA on suspicion of renovascular disease, blood was sampled during the procedure
      for measurement of hsCRP. The presence of atherosclerotic lesions was assessed at
      the level of the renal arteries and the abdominal aorta. Haemodynamically
      significant renal artery stenosis was diagnosed when 50% or more stenosis was
      observed. Patients with fibromuscular disease (n = 8) or incomplete data (n = 4)
      were excluded from analysis. The results revealed that the median hsCRP
      concentrations were significantly higher among the 57 patients with
      atherosclerosis of the aorta and/or renal arteries compared to those in the 26
      patients without any angiographic lesions (4.6 vs 1.7 mg/l; P < 0.005). Moreover,
      in patients with renal artery stenosis, levels of hsCRP were higher when the
      degree of stenosis exceeded 50%. However, the association between hsCRP and the
      presence of atherosclerosis appeared to be confounded by serum creatinine,
      creatinine clearance, age and gender. In the whole group a significant inverse
      relationship was found between creatinine clearance and hsCRP (P < 0.05). In
      conclusion, hsCRP concentrations are related to atherosclerotic lesions in the
      renal arteries and the abdominal aorta. While this supports the view that
      atherosclerotic renal artery stenosis is part of a systemic inflammatory vascular
      disease, increased concentrations of CRP may also coincide with decreased renal
      function.

PMID- 15944721
TI  - The impact of oral phenylpropanolamine on blood pressure: a meta-analysis and
      review of the literature.
AB  - Oral phenylpropanolamine is commonly used to treat congestion and obesity.
      Clinicians often wonder what effect it has on blood pressure and whether they are
      safe in hypertensive patients. The purpose of our systematic review was to assess
      whether these drugs cause clinically meaningful elevations in pulse or blood
      pressure. English-language, randomized, placebo-controlled trials of oral
      phenylpropanolamine in adults with extractable data on pulse or blood pressure
      were studied. MEDLINE (1966-2003), Embase, the Cochrane library and reviewed
      article references were used as sources. Systolic (SBP) and diastolic blood
      pressure (DBP) and heart rate data were extracted. Additional extracted data
      included demographics, year, study design, study duration, drug dose and
      frequency, duration of washout and country. Study quality was assessed using the
      methods of Jadad and data were synthesized using a random effects model using
      weighted mean differences. In all, 33 trials reporting 48 treatment arms with
      2165 patients were included. Phenylpropanolamine increased SBP 5.5 mmHg (95% CI:
      3.1-8.0) and DBP 4.1 mmHg (95% CI: 2.2-6.0) with no effect on pulse. Patients
      with controlled hypertension were not at greater risk of blood pressure
      elevation. Immediate release preparations had greater effects on blood pressure
      than sustained release ones. Higher doses and shorter duration use also caused
      greater increases. Eighteen studies contained at least one treated subjects
      having blood pressure elevations > or =140/90 mmHg, an increase in SBP > or =15
      mmHg or an increase in DBP > or =10 mmHg. In conclusion, phenylpropanolamine
      caused a small, but significant increase in systolic blood pressure. The effect
      was more pronounced with shorter-term administration, higher doses of medication
      and immediate release formulations.

PMID- 15944722
TI  - Birth weight, hypertension and "white coat" hypertension: size at birth in
      relation to office and 24-h ambulatory blood pressure.
AB  - We investigated the association of size at birth with hypertensive status defined
      by office blood pressure (BP) and 24-h ambulatory BP monitoring in a historical
      cohort study of 736 men born 1920-1924 and examined at age 70 years. Office BP
      was measured after 10-min supine rest with a sphygmomanometer, ambulatory BP was
      recorded with Accutracker 2, and anthropometric and other measurements were taken
      at a clinic. Birth weight and gestational age were abstracted from the men's
      birth records. A total of 24% of the men were treated for hypertension at the
      time of the study. Among not treated subjects, there was a weak positive
      association of birth weight with daytime and 24-h diastolic ambulatory BP. In
      subjects treated for hypertension, both office and ambulatory BP were inversely
      related to birth weight, although these associations were not statistically
      significant. Birth weight did not show significant association with sustained
      hypertension (elevated office and daytime ambulatory BPs) but showed a strong and
      statistically significant inverse association with "white coat" hypertension
      (elevated office BP and normal daytime ambulatory BP) when adjusted for
      concurrent body mass index (odds ratios 1.91, 1.59, 1 and 1.21 from lowest to
      highest quartile of birth weight, P-value for trend 0.035). We conclude that BP
      measured by 24-h-ambulatory monitoring is not related to birth weight in a
      pattern previously reported for office BP and that factors related to growth in
      utero are particularly related to higher risk of "white coat" hypertension.

PMID- 15944723
TI  - Home blood-pressure monitoring among hypertensive patients in an Asian
      population.
AB  - Hypertension is a principal cause of mortality and morbidity in Singapore. The
      use of home blood-pressure monitoring (HBPM) to assess hypertensive control with
      digital devices in the local multi-racial population is unknown. The study
      determined the factors associated with hypertensive patients' use of HBPM in
      primary care in a multi-racial Asian population. Randomized cross-sectional
      questionnaire survey of hypertensive patients managed in a district polyclinic. A
      model predicting use of HBPM was constructed by univariate and multivariate
      logistic regression. A total of 224 eligible subjects were randomly selected from
      1943 patients. Response rate was 78.1% (n = 175). In all, 61.7% of them were
      aware of HBPM but only 24% used HBPM. Using multivariate analysis by stepwise
      backward regression, the final fitted model showed that HBPM was associated with
      higher patients' socioeconomic status: (adjusted OR for middle-income status =
      2.85, 95% CI: 1.2-6.78, P = 0.018; adjusted OR for high-income status = 3.46, 95%
      CI: 1.22-9.87, P = 0.020) and their documented diastolic BP (adjusted OR for
      diastolic BP > 80 mmHg = 2.26, 95% CI: 1.06-4.82, P = 0.034). Nonusers cited
      failure to recognize benefits (54.1%), lack of HBPM awareness (29.3%),
      understanding of device operation (18.8%) and perception of inaccuracy (10.5%) as
      deterrents. 76.2% of users were satisfied with HBPM but lacked knowledge in
      maintenance of devices. In conclusion, 61.7% of the study population were aware
      of HBPM but only 24% used it. Patients' failure to recognize benefits, lack of
      awareness, cost and perception of inaccuracy were barriers. Higher socioeconomic
      status and patient's documented diastolic BP correlated with HBPM usage.

PMID- 15944724
TI  - Left ventricular filling abnormalities and obesity-associated hypertension:
      relationship with overproduction of circulating transforming growth factor beta1.
AB  - This study has been designed to evaluate the relationship among transforming
      growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a
      population of hypertensive subjects with normal left ventricular ejection
      fraction. We studied 67 hypertensive outpatients who according to their BMI
      levels were subdivided into three groups: lean (L), overweight (OW) and obese
      (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography
      was determined. All hypertensives were further subgrouped, according to European
      Society of Cardiology Guidelines, into two subsets of patients with normal
      diastolic function or with diastolic dysfunction. Prevalence of left ventricular
      hypertrophy (LVH) was determined in all the groups. TGFbeta1, left ventricular
      mass (LVM), LVM/h(2.7), E-wave deceleration time and isovolumic relaxation time
      (IVRT) were significantly (P < 0.005) higher and E/A velocity ratio was
      significantly (P < 0.05) lower in OW-HT and OB-HT than in L-HT. Prevalence of LVH
      was significantly higher (P < 0.03) in group OB-HT than in L-HT. TGFbeta1 (P <
      0.004), LVM/h(2.7) (P < 0.001) and prevalence of LVH were (P < 0.01)
      significantly higher in hypertensives with diastolic dysfunction than
      hypertensives with normal diastolic function. TGFbeta1 levels were positively
      correlated with BMI (r = 0.60; P < 0.0001), LVM/h(2.7) (r = 0.28; P < 0.03), IVRT
      (r = 0.30; P < 0.02) and negatively with E/A ratio (r = -0.38; P < 0.002) in all
      HT. Multiple regression analysis indicated that TGFbeta1, BMI and IVRT were
      independently related to E/A ratio explaining 71% of its variability (r = 0.84; P
      < 0.0001). This relationship was independent of LVH, age and HR suggesting that
      TGFbeta1 overproduction may be considered a pathophysiological mechanism in the
      development of left ventricular filling abnormalities in obesity-associated
      hypertension.

PMID- 15944725
TI  - Epidemiology of nosocomial infections in selected neonatal intensive care units
      in Colombia, South America.
AB  - OBJECTIVE: The epidemiology of nosocomial infections (NI) in neonatal intensive
      care units in developing countries has been poorly studied. We conducted a
      prospective study in selected neonatal units in Colombia, SA, to describe the
      incidence rate, causative organisms, and interinstitutional differences. STUDY
      DESIGN: Data were collected prospectively from February 20 to August 30, 2001
      from eight neonatal units. NI was defined as culture-proven infection diagnosed
      after 72 h of hospitalization, resulting in treatment with antibiotics for >3
      days. Linear regression models were used to describe associations between
      institutional variables and NI rates. RESULTS: A total of 1504 infants were
      hospitalized for more than 72 h, and therefore, at risk for NI. Of all, 127
      infections were reported among 80 patients (5.3%). The incidence density rate was
      6.2 per 1000 patient-days. Bloodstream infections accounted for 78% of NIs. Gram
      negative organisms predominated over gram-positive organisms (55 vs 38%) and were
      prevalent in infants < or =2000 g (54%). The most common pathogens were
      Staphylococcus epidermidis (26%) and Klebsiella pneumonia (12%). CONCLUSION: Gram
      negative organisms predominate in Colombia among infants <2000 g. The emergence
      of gram-negative organisms and their associated risk factors requires further
      study.

PMID- 15944726
TI  - Prevalence and correlates of sexual dysfunction among young adult married women
      in rural China: a population-based study.
AB  - The study investigates prevalence of sexual dysfunction (SD), sexual satisfaction
      and their correlates in the rural female population in China. An anonymous cross
      sectional study was carried out in a random sample of 1178 married of age 20-39
      years in Dengfeng County, Henan, China. The prevalence of having at least one SD
      was 43 and 38% of the respondents were satisfied with their sexual life; 64.0%
      thought that sex was not important to them; and 85.7% believed that they do not
      have adequate sex-related knowledge. Having SD and high sexual satisfaction were
      associated with high mental health or vitality quality of life scores and better
      perceived health status. Other independent predictors of SD included
      sociodemographic variables, biological variables, life style factors and
      masturbation. It is concluded that SD was prevalent among the studied women and
      were associated with mental health. The sexual health among married women needs
      to be improved in rural China.

PMID- 15944727
TI  - Priapism caused by 'All Nite Long'.

PMID- 15944728
TI  - Use of the hereditary persistence of fetal hemoglobin 2 enhancer to increase the
      expression of oncoretrovirus vectors for human gamma-globin.
AB  - The development of oncoretrovirus vectors for human gamma-globin has been
      hampered by problems of low expression and gene silencing. In order to address
      these problems, we investigated an enhancer element identified from individuals
      with deletional hereditary persistence of fetal hemoglobin 2 (HPFH2), a genetic
      condition characterized by elevated levels of gamma-globin in adults. Plasmid
      transfection studies in erythroid MEL (murine erythroleukemia) cells demonstrated
      the HPFH2 element could function synergistically with the beta-globin locus
      control region to enhance the expression of an Agamma-globin gene with a
      truncated -382 bp promoter. A series of oncoretrovirus vectors were subsequently
      generated that contain an expression cassette for Agamma-globin linked to various
      combinations of the HPFH2 enhancer, the alpha-globin HS40 enhancer, and several
      versions of the promoter from Agamma-globin or beta-globin. Expression analysis
      in transduced MEL cell clones revealed very high levels of promoter-autonomous
      silencing that was at least partially abrogated by the HPFH2 enhancer. The vector
      containing a combination of a -201 bp Agamma-globin gene promoter with the Greek
      HPFH -117 point mutation and both the HPFH2 and HS40 enhancers exhibited no signs
      of vector silencing and was expressed at 248+/-99% per copy of mouse alpha-globin
      (62% of total alpha-globin). This represents a significant improvement over
      previously reported oncoretrovirus vectors for Agamma-globin, and demonstrates
      the capacity of the HPFH2 enhancer to abrogate sequence-autonomous silencing of
      the Agamma-globin promoter in the context of a gene transfer vector.

PMID- 15944729
TI  - Adeno-associated virus (AAV)-7 and -8 poorly transduce vascular endothelial cells
      and are sensitive to proteasomal degradation.
AB  - Transduction of the vascular endothelium by adeno-associated virus (AAV) vectors
      would have broad appeal for gene therapy. However, levels of transduction by AAV
      serotype-2 are low, an observation linked to deficiencies in endothelial cell
      binding, sequestration of virions in the extracellular matrix and/or virion
      degradation by the proteasome. Strategies to improve transduction of endothelial
      cells include AAV-2 capsid targeting using small peptides isolated by phage
      display or the use of alternate serotypes. Previously, we have shown that AAV
      serotypes-3 through -6 transduce endothelial cells with poor efficiency.
      Recently, AAV serotypes-7 and -8 have been shown to mediate efficient
      transduction of the skeletal muscle and liver, respectively, although their
      infectivity profile for vascular cells has not been addressed. Here, we show that
      AAV-7 and -8 also transduce endothelial cells with poor efficiency and the levels
      of transgene expression are markedly enhanced by inhibition of the proteasome. In
      both cases proteasome blockade enhances the nuclear translocation of virions. We
      further show that this is vascular cell-type selective since transduction of
      smooth muscle cells is not sensitive to proteasome inhibition. Analysis in intact
      blood vessels corroborated these findings and suggests that proteasome
      degradation is a common limiting factor for endothelial cell transduction by AAV
      vectors.

PMID- 15944730
TI  - Optimization of adenovirus serotype 35 vectors for efficient transduction in
      human hematopoietic progenitors: comparison of promoter activities.
AB  - Adenoviral gene transfer to hematopoietic stem cells (HSCs)/progenitors would
      provide a new approach to the treatment of hematopoietic diseases and study of
      the hematopoietic system. We have previously reported that an adenovirus (Ad)
      vector composed of whole Ad serotype 35 (Ad35), which belongs to subgroup B,
      shows efficient gene transfer into human bone marrow CD34+ cells. However, Ad35
      vector-mediated transduction into human HSCs/progenitors has not yet been fully
      optimized. In the present study, we have systematically examined promoter
      activity in the context of Ad35 vectors in human bone marrow CD34+ cells and
      primitive CD34+ subsets to optimize the transduction efficiency in human
      hematopoietic stem/progenitor cells. In the first of the transduction
      experiments, the improved in vitro ligation method was applied to Ad35 vector
      construction to allow for simple and efficient production of an E1/E3-deleted
      Ad35 vector. Using this method, we constructed a series of Ad35 vectors encoding
      the enhanced green fluorescence protein (GFP) under the control of a variety of
      strong viral and cellular promoters. Of the six types of promoters tested,
      significantly higher transduction efficiencies were achieved with the human
      elongation factor 1alpha promoter (EF1alpha promoter), the human cytomegalovirus
      (CMV) immediate-early 1 gene enhancer/beta-actin promoter with beta-actin intron
      (CA promoter), and the CMV promoter/enhancer with the largest intron of CMV
      (intron A) (CMVi promoter) in the human CD34+ cells and the immature subsets
      (CD34+ CD38(low/-) and CD34+ AC133+ subsets). In particular, the CA promoter was
      found to allow for the highest transduction efficiencies in both the whole human
      CD34+ cells and the immature hematopoietic subsets. Furthermore, the CA promoter
      mediated GFP-expressing cells differentiated into progenitor cells of all
      lineages. These results indicate the construction of an optimized Ad35 vector
      backbone for efficient transduction into HSCs/progenitors.

PMID- 15944731
TI  - Regression of mouse tumours and inhibition of metastases following administration
      of a Semliki Forest virus vector with enhanced expression of IL-12.
AB  - The Semliki Forest virus (SFV) vector is an RNA-based suicide expression vector
      that has been used experimentally for tumour therapy. Recently, a new enhanced
      vector pSFV10-E has been developed that expresses foreign genes at levels up to
      10 times higher than the original vector. Interleukin-12 (IL-12), an
      immunomodulatory cytokine, plays a key role in the induction of T-helper1
      responses. The two IL-12 gene subunits were cloned from mouse splenocytes and
      inserted into the pSFV10-E and pSFV10 (non-enhanced) vectors. Both constructs
      expressed and secreted biologically active murine IL-12. Administration of high
      titre rSFV10-E-IL12 particles intratumourally to treat implanted K-BALB tumours
      in BALB/c mice demonstrated complete tumour regression in comparison to control
      or rSFV10-IL12 treated groups. High titre rSFV10-E-IL12 particles were also
      effective in the CT26 tumour model. Histological and immunohistochemical studies
      revealed tumour necrosis in addition to aggressive influx of CD4+ and CD8+ T
      cells and other immune cells. Furthermore, inhibition of primary tumour growth
      and lung metastases of a metastatic (4T1) tumour model indicated the potential of
      high titres of rSFV10-E-IL12 particles as an efficient antitumour therapeutic
      agent.

PMID- 15944732
TI  - Imiquimod and S-27609 as adjuvants of DNA vaccination in a transgenic murine
      model of HER2/neu-positive mammary carcinoma.
AB  - DNA vaccination against HER-2/neu is an effective way to induce an immune
      response able to oppose the spontaneous development of mammary tumours occurring
      in HER-2/neu transgenic mice. In this study, we have evaluated the potential of
      Imiquimod and the analogue S-27609 as adjuvants of DNA vaccination against HER
      2/neu in transgenic mice. The association of a DNA vaccine encoding a portion of
      rat HER2/neu with either Imiquimod or S-27609 was found to delay the development
      of spontaneous mammary tumours and to reduce their incidence, in comparison with
      DNA vaccination alone. Almost 80 or 40% of tumour-free mice were found at the end
      of measurement time in mice vaccinated and supplemented with Imiquimod or S
      27609, respectively. The antitumour preventive effect was associated with
      increased antibody and cell-mediated immune responsiveness against HER-2/neu. In
      mice vaccinated and supplemented with Imiquimod, a small but significant increase
      of rat p185neu-specific cytotoxicity and of IFN-gamma and IL-2-producing CD8T
      cells, together with a reduction of IL-4-producing CD4T cells, and a switch from
      an IgG1 towards a IgG2a phenotype of anti-p185neu antibodies, suggested a TH1
      polarization of the immune response. The immunoregulatory efficacy of S-27609 was
      lower than that observed for Imiquimod. These data highlight the potential of
      Imiquimod, and, to a lower extent, of S-27609, as immunological adjuvants of
      therapeutic DNA vaccines.

PMID- 15944733
TI  - Adeno-associated virus type 4 (AAV4) targets ependyma and astrocytes in the
      subventricular zone and RMS.
AB  - The subventricular zone (SVZ) is one of the neurogenic niches in the adult
      mammalian brain. The SVZ is of interest for studies on neurogenesis and stem cell
      therapy. Here, we report specific transduction of ependyma and/or astrocytes by
      recombinant adeno-associated virus type 4 (AAV4) viral vectors. AAV4 vectors
      encoding beta-galactosidase or eGFP were injected into the lateral ventricles of
      neonatal and adult C57BL/6 mouse brains. In addition, SVZ injections were
      conducted on adult mice. AAV4 vectors show a characteristic transduction of the
      ependyma independent of delivery route. However, AAV4 virus injected into the SVZ
      targeted GFAP positive astrocytes forming the glial tube in the SVZ and rostral
      migratory stream (RMS). Our results introduce AAV4 as a new tool by which to
      manipulate glial cells in the RMS.

PMID- 15944734
TI  - ArfGAP1 responds to membrane curvature through the folding of a lipid packing
      sensor motif.
AB  - ArfGAP1 promotes GTP hydrolysis in Arf1, a small G protein that interacts with
      lipid membranes and drives the assembly of the COPI coat in a GTP-dependent
      manner. The activity of ArfGAP1 increases with membrane curvature, suggesting a
      negative feedback loop in which COPI-induced membrane deformation determines the
      timing and location of GTP hydrolysis within a coated bud. Here we show that a
      central sequence of about 40 amino acids in ArfGAP1 acts as a lipid-packing
      sensor. This ALPS motif (ArfGAP1 Lipid Packing Sensor) is also found in the yeast
      homologue Gcs1p and is necessary for coupling ArfGAP1 activity with membrane
      curvature. The ALPS motif binds avidly to small liposomes and shows the same
      hypersensitivity on liposome radius as full-length ArfGAP1. Site-directed
      mutagenesis, limited proteolysis and circular dichroism experiments suggest that
      the ALPS motif, which is unstructured in solution, inserts bulky hydrophobic
      residues between loosely packed lipids and forms an amphipathic helix on highly
      curved membranes. This helix differs from classical amphipathic helices by the
      abundance of serine and threonine residues on its polar face.

PMID- 15944735
TI  - Altered nucleosome occupancy and histone H3K4 methylation in response to
      'transcriptional stress'.
AB  - We report that under 'transcriptional stress' in budding yeast, when most pol II
      activity is acutely inhibited, rapid deposition of nucleosomes occurs within
      genes, particularly at 3' positions. Whereas histone H3K4 trimethylation normally
      marks 5' ends of highly transcribed genes, under 'transcriptional stress' induced
      by 6-azauracil (6-AU) and inactivation of pol II, TFIIE or CTD kinases Kin28 and
      Ctk1, this mark shifted to the 3' end of the TEF1 gene. H3K4Me3 at 3' positions
      was dynamic and could be rapidly removed when transcription recovered. Set1 and
      Chd1 are required for H3K4 trimethylation at 3' positions when transcription is
      inhibited by 6-AU. Furthermore, Deltachd1 suppressed the growth defect of
      Deltaset1. We suggest that a 'transcriptional stress' signal sensed through Set1,
      Chd1, and possibly other factors, causes H3K4 hypermethylation of newly deposited
      nucleosomes at downstream positions within a gene. This response identifies a new
      role for H3K4 trimethylation at the 3' end of the gene, as a chromatin mark
      associated with impaired pol II transcription.

PMID- 15944736
TI  - TAp63alpha induces apoptosis by activating signaling via death receptors and
      mitochondria.
AB  - TP63, an important epithelial developmental gene, has significant homology to
      p53. Unlike p53, the expression of p63 is regulated by two different promoters
      resulting in proteins with opposite functions: the full-length transcriptionally
      active TAp63 and the dominant-negative DeltaNp63. We investigated the downstream
      mechanisms by which TAp63alpha elicits apoptosis. TAp63alpha directly
      transactivates the CD95 gene via the p53 binding site in the first intron
      resulting in upregulation of a functional CD95 death receptor. Stimulation and
      blocking experiments of the CD95, TNF-R and TRAIL-R death receptor systems
      revealed that TAp63alpha can trigger expression of each of these death receptors.
      Furthermore, our findings demonstrate a link between TAp63alpha and the
      mitochondrial apoptosis pathway. TAp63alpha upregulates expression of
      proapoptotic Bcl-2 family members like Bax and BCL2L11 and the expression of
      RAD9, DAP3 and APAF1. Of clinical relevance is the fact that TAp63alpha is
      induced by many chemotherapeutic drugs and that inhibiting TAp63 function leads
      to chemoresistance. Thus, beyond its importance in development and
      differentiation, we describe an important role for TAp63alpha in the induction of
      apoptosis and chemosensitivity.

PMID- 15944739
TI  - Universities, governments and industry: can the essential nature of universities
      survive the drive to commercialize?

PMID- 15944737
TI  - Essential role of Hrs in a recycling mechanism mediating functional
      resensitization of cell signaling.
AB  - Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is well known
      to terminate cell signaling by sorting activated receptors to the MVB/lysosomal
      pathway. Here we identify a distinct role of Hrs in promoting rapid recycling of
      endocytosed signaling receptors to the plasma membrane. This function of Hrs is
      specific for receptors that recycle in a sequence-directed manner, in contrast to
      default recycling by bulk membrane flow, and is distinguishable in several ways
      from previously identified membrane-trafficking functions of Hrs/Vps27p. In
      particular, Hrs function in sequence-directed recycling does not require other
      mammalian Class E gene products involved in MVB/lysosomal sorting, nor is
      receptor ubiquitination required. Mutational studies suggest that the VHS domain
      of Hrs plays an important role in sequence-directed recycling. Disrupting Hrs
      dependent recycling prevented functional resensitization of the beta(2)
      adrenergic receptor, converting the temporal profile of cell signaling by this
      prototypic G protein-coupled receptor from sustained to transient. These studies
      identify a novel function of Hrs in a cargo-specific recycling mechanism, which
      is critical to controlling functional activity of the largest known family of
      signaling receptors.

PMID- 15944738
TI  - A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible
      chloroquine resistance.
AB  - Chloroquine resistance (CQR) in Plasmodium falciparum is associated with
      mutations in the digestive vacuole transmembrane protein PfCRT. However, the
      contribution of individual pfcrt mutations has not been clarified and other genes
      have been postulated to play a substantial role. Using allelic exchange, we show
      that removal of the single PfCRT amino-acid change K76T from resistant strains
      leads to wild-type levels of CQ susceptibility, increased binding of CQ to its
      target ferriprotoporphyrin IX in the digestive vacuole and loss of verapamil
      reversibility of CQ and quinine resistance. Our data also indicate that PfCRT
      mutations preceding residue 76 modulate the degree of verapamil reversibility in
      CQ-resistant lines. The K76T mutation accounts for earlier observations that CQR
      can be overcome by subtly altering the CQ side-chain length. Together, these
      findings establish PfCRT K76T as a critical component of CQR and suggest that CQ
      access to ferriprotoporphyrin IX is determined by drug-protein interactions
      involving this mutant residue.

PMID- 15944741
TI  - Selective GABAergic treatment for panic? Investigations in experimental panic
      induction and panic disorder.
AB  - gamma-Aminobutyric acid (GABA) is the most important inhibitory neurotransmitter
      in the central nervous system (CNS). It exerts its rapid inhibitory action mostly
      through GABA(A) receptors, which are targets for benzodiazepines, barbiturates,
      neuroactive steroids and distinct anticonvulsive agents. There is considerable
      evidence that dysfunction of GABA(A) receptors or dysregulation of GABA
      concentrations in the CNS (or both) plays an important role in the
      pathophysiology of panic disorder. Currently, benzodiazepines are the only drugs
      directly targeting the GABA(A) receptors that are approved for the treatment of
      anxiety disorders. Because of their well-known anxiolytic effects, they are
      widely used in this setting, but side effects limit their use in long-term
      treatment. The question of whether drugs that selectively increase GABA
      concentrations in the CNS could improve symptoms of anxiety has been discussed.
      Recent investigations by our group have demonstrated that enhancement of
      endogenous GABA (through blockade of GABA transaminase by vigabatrin or through
      inhibition of GABA transporters by tiagabine) exerts anxiolytic effects on
      experimentally induced panic. Our studies in healthy volunteers have shown that
      both compounds lead to a significant reduction in panic symptoms elicited by
      cholecystokinin-tetrapeptide. Moreover, benzodiazepine-like effects on the
      activity of the hypothalamic-pituitary-adrenal axis have been observed in
      association with vigabatrin treatment. Small open studies in patients with panic
      disorder also showed an improvement in panic and anxiety with both compounds.
      This review summarizes our recent research on the effects of selective GABAergic
      treatment in experimentally induced panic and outlines the possible role of
      compounds targeting the GABA binding site of the GABA(A)-benzodiazepine receptor
      for the treatment of panic and anxiety.

PMID- 15944742
TI  - Is the cerebellum relevant in the circuitry of neuropsychiatric disorders?
AB  - Contemporary mechanistic models of several psychiatric disorders propose
      abnormalities in the structure and function of distinct neural networks. The
      cerebellum has both anatomic and functional connections to the prefrontal cortex,
      the subcortical limbic structures and monoamine-producing brainstem nuclei.
      Conspicuously, however, the cerebellum has been underemphasized in
      neuropsychiatric research. A growing confluence of scientific data indicate that
      the cerebellum may not be irrelevant, which suggests that an integrated model of
      neuropsychiatric disorders should include a role for the cerebellum and its
      relevant neural connections. This review summarizes the published data describing
      and characterizing the putative role of the cerebellum in normal and abnormal
      mood regulation, with specific attention to states of psychosis, depression and
      mania. The available evidence suggests that a functional role for the cerebellum
      should be considered in future neuropsychiatric studies.

PMID- 15944743
TI  - Comorbidity and pathophysiology of obsessive-compulsive disorder in
      schizophrenia: is there evidence for a schizo-obsessive subtype of schizophrenia?
AB  - Epidemiologic and neurobiologic evidence suggests that patients with comorbid
      obsessive-compulsive disorder (OCD) and schizophrenia may represent a special
      category among patients with schizophrenia. Efforts to examine the neurobiology
      of this group have focused on neuroimaging studies and neuropsychologic testing.
      Convergent evidence suggests that there may be a specific pattern of
      neurobiologic dysfunction in this subgroup of patients accounting for symptom co
      expression. This review indicates that future studies should distinguish among
      (1) apparent obsessive-compulsive symptoms (OCS) that occur only in the context
      of psychosis and that may overlap with psychotic phenomenology, representing a
      forme fruste of psychosis; (2) OCS occurring only in the prodromal phase of
      schizophrenia; (3) neuroleptic-induced OCS or OCD; and (4) OCS or frank OCD
      occurring concurrently with schizophrenia. We examine the evidence for a putative
      schizo-obsessive disorder and outline suggestions for identifying OCS in the
      presence of psychosis.

PMID- 15944744
TI  - Amitriptyline and fluoxetine protect PC12 cells from cell death induced by
      hydrogen peroxide.
AB  - OBJECTIVE: To investigate the potential protective effects of amitriptyline and
      fluoxetine in a catecholamine cell model. METHODS: Cultured rat pheochromocytoma
      (PC12) cells were pretreated with amitriptyline or fluoxetine for 24 or 48 hours
      and were then subjected to neurotoxic insult (200 micromol/L hydrogen peroxide).
      Cell viability was determined by measurement of the reduction product of 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). The enzyme activity
      of superoxide dismutase (SOD) was determined by a commercial SOD assay kit.
      RESULTS: The decrease in cell viability induced by hydrogen peroxide was
      attenuated in PC12 cells pretreated with 100 micromol/L amitriptyline for 24
      hours or with 50 micromol/L amitriptyline or 50 micromol/L fluoxetine for 48
      hours. Pretreatment with either amitriptyline or fluoxetine was associated with
      increased SOD activity in PC12 cells. Inhibition of SOD activity with
      diethyldithiocarbamic acid reduced the cytoprotective action of fluoxetine.
      CONCLUSIONS: These data suggest that the neuroprotective actions of some
      antidepressants include the upregulation of SOD activity.

PMID- 15944745
TI  - Loudness dependence of the auditory evoked potential and response to
      antidepressants in Chinese patients with major depression.
AB  - OBJECTIVE: To investigate the loudness dependence of the auditory evoked
      potential (LDAEP) in predicting response to treatment for major depression.
      METHODS: One hundred patients of Chinese ethnicity with major depression were
      divided into 2 groups, having strong or weak pretreatment LDAEP; the cutoff was
      the median of the LDAEP slope (for amplitude as a function of intensity). There
      were no between-group differences before treatment in terms of score on the
      Hamilton Depression Rating Scale (HDRS), age or sex distribution. The LDAEP for 4
      intensity levels (60, 70, 80 and 90 dB) was recorded before treatment. Each
      patient then received fluoxetine 20 mg per day for 4 weeks. The response to
      treatment was evaluated by means of the HDRS. RESULTS: At week 4, the HDRS score
      had declined by 44.3; for the group with strong LDAEP and by 34.4% for the group
      with weak LDAEP (t for mean difference = 2.584, p = 0.011). CONCLUSION: Strong
      pretreatment LDAEP predicted a favourable response to treatment with a selective
      serotonin reuptake inhibitor in patients with major depression.

PMID- 15944746
TI  - What are the treatment options for comorbid alcohol abuse and depressive
      disorders?

PMID- 15944747
TI  - Advances in atherosclerosis: new treatments, new targets. A report from the 75th
      European Atherosclerosis Society Annual Meeting.

PMID- 15944748
TI  - Adrenomedullin as a potent antioxidative and antiatherosclerotic substance.
AB  - Adrenomedullin was originally discovered as a vasodilative peptide, but recent
      studies have revealed its pleiotropic effects. Among these studies, the
      antioxidative properties of adrenomedullin were observed in adrenomedullin
      knockout mice. Through its antioxidative effect, adrenomedullin can protect
      organs from damage induced by high blood pressure, ischemia and aging. This
      indicates that antioxidants that can inhibit reactive oxygen species production
      but do not have a scavenging effect could be a new effective therapeutic target
      for organ protection in hypertension as well as metabolic syndrome, in which
      higher oxidative stress plays a pivotal role.

PMID- 15944749
TI  - Inflammatory biomarkers and statins.
AB  - The concept of atherosclerosis as an inflammatory disorder has led to the
      exploration of new pathogeneses of this disease. In this regard, the levels of
      several inflammatory molecules are frequently increased in subjects at high risk
      of developing an acute coronary event. With a simple analysis we can characterize
      the circulating levels of a marker and its therapeutic modulation with various
      drugs. In this review we have analyzed different inflammatory markers currently
      used, such as C-reactive protein (CRP), CD40 ligand, adhesion molecules and
      chemokines, and their possible modulation by therapeutic intervention with 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Moreover, in
      the future, new technologies will allow us to discover new markers, or sets of
      them, that could indicate the direction to be taken in the prevention and
      treatment of cardiovascular diseases.

PMID- 15944750
TI  - Purification and partial characterization of beta-glucosidase from fresh leaves
      of tea plants (Camellia sinensis (L.) O. Kuntze).
AB  - beta-Glucosidases are important in the formation of floral tea aroma and the
      development of resistance to pathogens and herbivores in tea plants. A novel beta
      glucosidase was purified 117-fold to homogeneity, with a yield of 1.26%, from tea
      leaves by chilled acetone and ammonium sulfate precipitation, ion exchange
      chromatography (CM-Sephadex C-50) and fast protein liquid chromatography (FPLC;
      Superdex 75, Resource S). The enzyme was a monomeric protein with specific
      activity of 2.57 U/mg. The molecular mass of the enzyme was estimated to be about
      41 kDa and 34 kDa by SDS-PAGE and FPLC gel filtration on Superdex 200,
      respectively. The enzyme showed optimum activity at 50 deg;C and was stable at
      temperatures lower than 40 degrees C. It was active between pH 4.0 and pH 7.0,
      with an optimum activity at pH 5.5, and was fairly stable from pH 4.5 to pH 8.0.
      The enzyme showed maximum activity towards pNPG, low activity towards pNP
      Galacto, and no activity towards pNP-Xylo.

PMID- 15944751
TI  - Cloning and identification of methionine synthase gene from Pichia pastoris.
AB  - Methionine synthase (MS) is grouped into two classes. Class One MS (MetH) and
      Class Two MS (MetE) share no homology and differ in their catalytic model. Based
      on the conserved sequences of metE genes from different organisms, a segment of
      the metE gene was first cloned from Pichia pastoris genomic DNA by PCR, and its
      5' and 3' regions were further cloned by 5'- and 3'-rapid amplification of cDNA
      ends (RACE), respectively. The assembled sequence reveals an open reading frame
      encoding a polypeptide of 768 residues, and the deduced product shares 76%
      identity with MetE of Saccharomyces cerevisiae. P. pastoris methionine synthase
      (PpMetE) consists of two domains common to MetEs. The active site is located in
      the C-terminal domain, in which the residues involved in the interaction of zinc
      with substrates are conserved. Homologous expression of PpMetE in P. pastoris was
      achieved, and the heterologous expression of PpMetE in the S. cerevisiae strain
      XJB3-1D that is MetE-defective restored the growth of the mutant on methionine
      free minimal media. The gene sequence has been submitted to GenBank/EMBL/DDBJ
      under accession No. AY601648.

PMID- 15944752
TI  - Carboxyfluorescein diacetate succinimidyl ester fluorescent dye for cell
      labeling.
AB  - Our objective was to study the properties of the carboxyfluorescein diacetate
      succinimidyl ester (CFDA-SE) and the methodology of cell labeling using CFDA-SE
      fluorescent dye. First, we analyzed the kinetics of CFDA-SE fluorescent dye
      intensity over time. Second, we determined the optimal concentration of CFDA-SE
      fluorescent dye for cell labeling. Third, we tested the toxicity of CFDA-SE
      fluorescent dye on labeled cells. Finally, we determined the optimal staining
      time of CFDA-SE fluorescent dye for cell labeling. The results show that the
      optimal concentration of CFDA-SE fluorescent dye for cell labeling varies
      according to different cell types. CFDA-SE fluorescent dye is non-toxic to cells
      as the cell death rate caused by CFDA-SE labeling is below 5%. The optimal cell
      labeling time was determined to be 8 min of incubation with CFDA-SE fluorescent
      dye. We concluded that the advantages of using CFDA-SE fluorescent dye for cell
      labeling are as follows: (1) the binding of CFDA-SE fluorescent dye to cells is
      stable; (2) CFDA-SE fluorescent dye is not toxic and does not modify the
      viability of labeled cells; and (3) CFDA-SE fluorescent dye is a suitable
      fluorochrome for cell labeling.

PMID- 15944753
TI  - Dose-dependent inhibition of gynecophoral canal protein gene expression in vitro
      in the schistosome (Schistosoma japonicum) by RNA interference.
AB  - The gynecophoral canal protein gene SjGCP of Schistosoma japonicum that is
      necessary for the pairing between the male and female worms is specifically
      expressed in the adult male worm. This protein is widely distributed in the adult
      female worm after pairing. Reverse transcription-polymerase chain reaction (RT
      PCR) and immunofluorescence were employed to analyze the relationship between the
      RNAi effect and dsRNA dosage in the parasites. The results revealed that the
      inhibition of SjGCP expression by siRNA is dose-dependent. RT-PCR analysis showed
      that the SjGCP transcript level was reduced by 75% when 100 nM dsRNA was applied.

PMID- 15944754
TI  - Non-invasive in situ simultaneous measurement of multi-parameter mechanical
      properties of red blood cell membrane.
AB  - The purpose of this study was to develop a new dynamic image analyzing technique
      that will give us the ability to measure the viscoelastic parameters of
      individual living red blood cells non-invasively, in situ and in real time. With
      this technique, the bending modulus KC, the shear elasticity mu and their ratio
      were measured under different temperatures, oxygen partial pressures and osmotic
      pressures. The results not only show the effects of external conditions on
      mechanical properties of cell membranes including deformability, flexibility,
      adhesive ability and plasticity, but also demonstrate that the technique can be
      used to measure cell membrane parameters continuously under several physiological
      and pathological conditions.

PMID- 15944755
TI  - Molecular cloning of a novel mouse testis-specific spermatogenic cell apoptosis
      inhibitor gene mTSARG7 as a candidate oncogene.
AB  - A novel mouse gene, mTSARG7 (GenBank accession No. AY489184), with a full cDNA
      length of 2279 bp and containing 12 exons and 11 introns, was cloned from a mouse
      expressed sequence tag (GenBank accession No. BE644543) that was significantly up
      regulated in cryptorchidism. The gene was located in mouse chromosome 8A1.3 and
      encoded a protein containing 403 amino acid residues that was a new member of the
      acyltransferase family because the sequence contained the highly conserved
      phosphate acyltransferase (PlsC) domain existing in all acyltransferase-like
      proteins. The mTSARG7 protein and AU041707 protein shared 83.9% identity in 402
      amino acid residues. Expression of the mTSARG7 gene was restricted to the mouse
      testis. The results of the in situ hybridization analysis revealed that the
      mTSARG7 mRNA was expressed in mouse spermatogonia and spermatocytes. Subcellular
      localization studies showed that the EGFP-tagged mTSARG7 protein was localized in
      the cytoplasm of GC-1 spg cells. The mTSARG7 mRNA expression was initiated in the
      mouse testis in the second week after birth, and the expression level increased
      steadily with spermatogenesis and sexual maturation of the mouse. The results of
      the heat stress experiment showed that the mTSARG7 mRNA expression gradually
      decreased as the heating duration increased. The pcDNA3.1 Hygro(-)/mTSARG7
      plasmid was constructed and introduced into GC-1 spg cells by liposome
      transfection. The mTSARG7 can accelerate GC-1 spg cells, causing them to traverse
      the S-phase and enter the G2-phase, compared with the control group where this
      did not occur as there was no transfection of mTSARG7. In conclusion, our results
      suggest that this gene may play an important role in spermatogenesis and the
      development of cryptorchid testes, and is a testis-specific apoptosis candidate
      oncogene.

PMID- 15944756
TI  - Anaerobic induction of isocitrate lyase and malate synthase in submerged rice
      seedlings indicates the important metabolic role of the glyoxylate cycle.
AB  - The glyoxylate cycle is a modified form of the tricarboxylic acid cycle that
      converts C2 compounds into C4 dicarboxylic acids at plant developmental stages.
      By studying submerged rice seedlings, we revealed the activation of the
      glyoxylate cycle by identifying the increased transcripts of mRNAs of the genes
      of isocitrate lyase (ICL) and malate synthase (MS), two characteristic enzymes of
      the glyoxylate cycle. Northern blot analysis showed that ICL and MS were
      activated in the prolonged anaerobic environment. The activity assay of pyruvate
      decarboxylase and ICL in the submerged seedlings indicated an 8.8-fold and 3.5
      fold increase over that in the unsubmerged seedlings, respectively. The activity
      assay of acetyl-coenzyme A synthetase in the submerged seedlings indicated a 3
      fold increase over that in the unsubmerged seedlings, which is important for
      initiating acetate metabolism. Consequently, we concluded that the glyoxylate
      cycle was involved in acetate metabolism under anaerobic conditions.

PMID- 15944757
TI  - Generation and characterization of C305, a murine neutralizing scFv antibody that
      can inhibit BLyS binding to its receptor BCMA.
AB  - B-lymphocyte stimulator (BLyS) is a member of the tumor necrosis factor (TNF)
      family and a key regulator of B cell response. Neutralizing single-chain fragment
      variable (scFv) antibody against BLyS binding to its receptor BCMA has the
      potential to play a prominent role in autoimmune disease therapy. A phage display
      scFv library constructed on pIII protein of M13 filamentous phage was screened
      using BLyS. After five rounds of panning, their binding activity was
      characterized by phage-ELISA. Nucleotide sequencing revealed that at least two
      different scFv gene fragments (C305 and D416) were obtained. The two different
      scFv gene fragments were expressed to obtain the soluble scFv antibodies, then
      the soluble scFv antibodies were characterized by means of competitive ELISA and
      in vitro neutralization assay. The results indicated that C305 is the
      neutralizing scFv antibody that can inhibit BLyS binding to its receptor BCMA.

PMID- 15944758
TI  - Role of oxyR from Sinorhizobium meliloti in regulating the expression of
      catalases.
AB  - The process of symbiotic nitrogen fixation results in the generation of reactive
      oxygen species such as the superoxide anion (O2-) and hydrogen peroxide (H2O2).
      The response of rhizobia to these toxic oxygen species is an important factor in
      nodulation and nitrogen fixation. In Sinorhizobium meliloti, one oxyR homologue
      and three catalase genes, katA, katB, and katC were detected by sequence
      analysis. This oxyR gene is located next to and divergently from katA on the
      chromosome. To investigate the possible roles of oxyR in regulating the
      expression of catalases at the transcriptional level in S. meliloti, an insertion
      mutant of this gene was constructed. The mutant was more sensitive and less
      adaptive to H2O2 than the wild type strain, and total catalase/peroxidase
      activity was reduced approximately fourfold with the OxyR mutation relative to
      controls. The activities of KatA and KatB and the expression of katA::lacZ and
      katB::lacZ promoter fusions were increased in the mutant strain compared with the
      parental strain grown in the absence of H2O2, indicating that katA and katB are
      repressed by OxyR. However, when exposed to H2O2, katA expression was also
      increased in both S. meliloti and Escherichia coli. When exposed to H2O2, OxyR is
      converted from a reduced to an oxidized form in E. coli. We concluded that the
      reduced form of OxyR functions as a repressor of katA and katB expression. Thus,
      in the presence of H2O2, reduced OxyR is converted to the oxidized form of OxyR
      that then results in increased katA expression. We further showed that oxyR
      expression is autoregulated via negative feedback.

PMID- 15944759
TI  - Quantitative transcript analysis in plants: improved first-strand cDNA synthesis.
AB  - The quantity and quality of first-strand cDNA directly influence the accuracy of
      transcriptional analysis and quantification. Using a plant-derived alpha-tubulin
      as a model system, the effect of oligo sequence and DTT on the quality and
      quantity of first-strand cDNA synthesis was assessed via a combination of semi
      quantitative PCR and real-time PCR. The results indicated that anchored oligo dT
      significantly improved the quantity and quality of alpha-tubulin cDNA compared to
      the conventional oligo dT. Similarly, omitting DTT from the first-strand cDNA
      synthesis also enhanced the levels of transcript. This is the first time that a
      comparative analysis has been undertaken for a plant system and it shows
      conclusively that small changes to current protocols can have very significant
      impact on transcript analysis.

PMID- 15944760
TI  - The role of heparanase in gastrointestinal cancer (Review).
AB  - Heparanase is endoglycosidase that degrades heparan sulfate, the main
      polysaccharide constituent of the extracellular matrix and basement membrane.
      Heparanase has been thought to have an important role in the process of cancer
      invasion and metastasis. Recent studies have revealed that heparanase has
      multifunctional modulatory effects in the progression of cancer cells and the
      cell-to-extracellular matrix interaction. Our recent research has shown the
      important roles of heparanase in the progression of esophagus, stomach and colon
      cancer, and heparanase expression was closely related to the prognosis of
      gastrointestinal cancer. Therapies targeting heparanase may result in promising
      tactics in cancer therapies. Heparanase gene silencing and inhibiton of enzymatic
      activities have potential use as targets for anticancer drug development. Here,
      we reviewed the role of heparanase in gastrointestinal tract tumors.

PMID- 15944761
TI  - Effects of vanadium complexes on cell growth of human leukemia cells and protein
      DNA interactions.
AB  - Vanadium complexes are known to possess potent insulin-mimetic effects, high
      affinity for several enzymes and anticancer activity, which deserve increasing
      attention for application to biomedical sciences. Different vanadium complexes
      have been found to be more effective than the simple vanadium-(IV) and -(V) salts
      in experiments performed both in vitro and in vivo. Application of
      polyoxometalates as potential drugs against Herpes Simplex Virus and AIDS have
      also increased the interest to study the association between vanadium containing
      species and proteins. The aim of our research was to investigate the in vitro
      antiproliferative activity of a variety of vanadium-containing compounds, and
      study their ability to interfere with the molecular interactions between GATA-1
      and NF-kappaB transcription factors and target DNA elements, employing
      electrophoretic mobility shift assays. All of the used vanadium compounds were
      found to exhibit antiproliferative activity, despite with differences in
      efficacy. Inhibition of K562 cell growth was not associated with differentiation,
      but with activation of apoptosis. Vanadium complexes with a +5 oxidation state
      and their discrete anionic units appear essential for the respective effects on
      K562 cells; a +4 oxidation state appears to be important in inhibiting
      transcription factors/DNA interactions.

PMID- 15944762
TI  - Loss of expression of oestrogen receptor beta in colon cancer and its association
      with Dukes' staging.
AB  - Gender differences in the incidence and behaviour of colon cancer suggest a
      hormonal influence and epidemiological data suggest a protective effect for
      hormone replacement therapy. Recently, it has been shown that oestrogen receptor
      (ER) beta is the predominant ER in colon tissue. The aim of this study was to
      examine the expression and distribution of ERbeta in normal and colorectal cancer
      samples, using immunohistochemistry and (in a subset of patients) real-time
      quantitative reverse transcriptase polymerase chain reaction in a well-defined
      patient cohort and to correlate this with clinico-pathological outcome.
      Immunohistochemical analyses of normal colon revealed strong specific nuclear
      immuno-reactivity in all epithelial cells lining the colonic crypts. In colon
      cancer, ERbeta expression was lost in 21% of samples irrespective of patient age
      or gender. Interestingly loss of ERbeta expression was higher in left colon and
      rectal cancers (27%) compared to right colon cancers (8%). A correlation between
      loss of ERbeta expression and advanced Dukes stage was observed. Loss of ERbeta
      with increased Dukes' stage suggests that it may be affording a protective effect
      against colon carcinogenesis. Its presence may be a favourable prognostic marker
      in this disease and could explain the protective effect of oestrogens against
      colon cancer development.

PMID- 15944763
TI  - Detailed chromosomal characterization of the breast cancer cell line MCF7 with
      special focus on the expression of the serine-threonine kinase 15.
AB  - Although the cell line MCF7 is widely used in breast cancer research, its
      cytogenetic properties have not been thoroughly investigated so far. As
      conventional G-banding analysis cannot resolve the complex chromosome
      aberrations, we investigated MCF7 cells using molecular-cytogenetic methods, with
      particular attention to the DNA amplification site on chromosome 20q. With
      spectral karyotyping we found numerous unbalanced chromosome translocations, and
      with comparative genomic hybridization we detected many quantitative genomic
      imbalances. Furthermore, we analyzed the amplified region at 20q with the
      candidate tumour susceptibility gene STK15 in detail by fluorescence in situ
      hybridization, whole chromosome painting, immunohistochemistry, Western blot and
      expression analysis. In MCF7 interphase cells we found increased copy number of
      the STK15 gene associated with overexpression of STK15 mRNA. Accordingly, STK15
      protein is overexpressed as compared to normal human fibroblasts in Western blot
      analysis. Overexpression of STK15 mRNA and protein is disproportionally stronger
      than that expected from the single additional copy of the STK15 gene. These data
      indicate that the highly increased level of STK15 protein in MCF7 cannot be
      explained by gene amplification alone. Apparently, secondary mechanisms of gene
      up-regulation are involved. This observation may be of general interest with
      regard to the activation of oncogenes in tumour cells.

PMID- 15944764
TI  - Correlations between antitumor activities of fluoropyrimidines and DPD activity
      in lung tumor xenografts.
AB  - The purposes of this study were to evaluate the antitumor activity of S-1 (1 M
      tegafur, 0.4 M 5-chloro-2,4-dihydroxypyridine and 1 M potassium oxonate) on human
      lung tumor xenografts, as compared with other fluoro-pyrimidines, and to
      investigate the relationships between fluoropyrimidine antitumor activities and
      four distinct enzymatic activities involved in the phosphorylation and
      degradation pathways of 5-fluorouracil (5-FU) metabolism. S-1, UFT (1 M tegafur-4
      M uracil), 5'-deoxy-5-fluorouridine (5'-DFUR), capecitabine and 5-FU were
      administered for 14 consecutive days to nude mice bearing lung tumor xenografts.
      S-1 showed stronger tumor growth inhibition in four of the seven tumors than the
      other drugs. Cluster analysis, on the basis of antitumor activity, indicated that
      S-1/UFT and 5'-DFUR/capecitabine/5-FU could be classified into another group. We
      investigated tumor thymidylate synthase content, dihydropyrimidine dehydrogenase
      (DPD) activity, thymidine phosphorylase (TP) activity and orotate phosphoribosyl
      transferase activity in seven human lung tumor xenografts and performed
      regression analyses for the antitumor activities of fluoropyrimidines. There were
      inverse correlations between antitumor and DPD activities for 5'-DFUR (r=-0.79,
      P=0.034), capecitabine (r=-0.56, P=0.19) and 5-FU (r=-0.86, P=0.013). However, no
      such correlations were observed for S-1 and UFT. These findings suggest that S-1
      containing a potent DPD inhibitor may have an antitumor effect on lung tumors,
      with high basal DPD activity, superior to those of other fluoropyrimidines.

PMID- 15944765
TI  - Differentiation and apoptosis in human malignant melanoma G-361 cells induced by
      2-aminophenoxazine-3-one.
AB  - Inhibitory effects of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3
      one (Phx-1), 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx
      2) and 2-aminophenoxazine-3-one (Phx-3), which were produced by the reaction of o
      aminophenol and its derivatives with bovine hemoglobin, on the proliferation of
      human malignant melanoma G-361 cells were studied under various conditions. Phx-1
      and Phx-3 showed anti-proliferative effects on human malignant melanoma G-361
      cells, however Phx-2 did not. Phx-3, which exerted the strongest anti
      proliferative effects, inhibited the proliferation of human malignant melanoma G
      361 cells during 24 h incubation at concentrations of >or=10 microM. Apoptosis
      and G1 arrest in the cells, which were detected by DNA laddering on
      electrophoresis and flow cytometry, respectively, were observed when the melanoma
      G-361 cells were treated with Phx-3 at 37 degrees C for 24 h. Concomitantly, the
      increased melanin formation in G-361 cells was indicated by biochemical and
      morphological detection of melanin within 24 h exposure to Phx-3. The present
      results suggest that Phx-3 exclusively demonstrates anti-tumor activity against
      human malignant melanoma G-361 cells by inducing cell cycle accumulation at G1,
      differentiation and apoptosis.

PMID- 15944766
TI  - Multiple endocrine neoplasia type 1 gene mutations in sporadic gastrinomas in
      Japan.
AB  - The molecular mechanisms responsible for the development and/or progression of
      gastrinomas are largely unknown. Studies involving sporadic enteropancreatic
      neuro-endocrine tumors suggest that mutations in the MEN1 gene occur in some
      tumors and probably play an important role in their pathogenesis. In this study,
      we examined whether somatic mutations in the MEN1 gene are also responsible for
      sporadic gastrinomas and correlate with clinical manifestations of gastrinomas in
      Japanese patients. Genomic DNA was extracted from paraffin-embedded gastrinoma
      tissues from 12 patients. Nucleotide sequences in the MEN1 genes were determined
      by direct sequencing. We identified 6 mutations in 7 out of 12 examined
      gastrinomas (58%). The identified mutations were 1 non-sense, 2 missense, 1
      deletion leading to frame shifts, 1 insertion and 1 splicing mutation. Identical
      mutations were found in three gastrinoma tissues. The age at surgery, the rate of
      hepatic metastasis, and tumor status were not significantly different in the 2
      groups. This study demonstrates that alterations in the MEN1 gene are involved in
      about half of all sporadic gastrinomas, although no correlation between the
      presence of mutations and location and clinical phenotype or severity of disease
      has been found.

PMID- 15944767
TI  - Enhancement of antitumor activity of 5'-deoxy-5-fluorouridine (Furtulon) by
      taxane in human gastric cancer xenografts.
AB  - 5'-deoxy-5-fluorouridine (5'-DFUR, Furtulon) is activated to 5-fluorouracil (5
      FU) by thymidine phosphorylase (dThdPase) highly expressed in many types of
      tumors. In previous studies, we demonstrated that taxanes (paclitaxel or
      docetaxel) up-regulated the tumor levels of dThdPase and enhanced the efficacy of
      5'-DFUR in human colon and mammary xenograft models. In the present study,
      combination therapy of 5'-DFUR with taxanes in human gastric cancer xenograft
      models also showed, at the least, additive anti-tumor activity without
      significant augmentation of toxicity. Furthermore, paclitaxel up-regulated
      dThdPase expression in the tumor tissues as confirmed with ELISA and
      immunohistochemistry. These results suggest taxanes would potentiate the efficacy
      of 5'-DFUR by up-regulating the tumor levels of dThdPase in gastric xenograft
      models. Clinical trials of 5'-DFUR in combination with taxane against gastric
      cancer are warranted.

PMID- 15944768
TI  - KAI1 inhibits anchorage-dependent and -independent pancreatic cancer cell growth.
AB  - Decreased expression of the tumor suppressor gene, KAI1, is associated with
      metastasis formation in pancreatic cancer. The aim of the present study was to
      investigate whether KAI1 influences pancreatic cancer cell growth and colony
      formation. A full-length KAI1 cDNA expression vector was stably transfected into
      Panc-1 and MiaPaCa-2 pancreatic cancer cell lines. Transfection was confirmed by
      Western blot analysis and immunohistochemistry. Tumor cell growth and cell cycle
      distribution were determined by MTT cell growth assays, colony formation assays,
      and flow cytometric analysis. KAI1-transfected, but not control-transfected
      pancreatic cancer cells displayed cytoplasmic KAI1 immunoreactivity. Cell
      proliferation decreased in the KAI1-transfected cells compared to parental and
      control cells together with a Go/G1-phase cell cycle arrest. Colony formation was
      reduced by 2.6- and 3.5-fold in the KAI1-transfected Panc-1 and MiaPaCa-2
      pancreatic cancer cells, respectively, compared with parental cells. KAI1 blocks
      pancreatic cancer cell growth through cell cycle arrest and inhibits anchorage
      independent cell growth. These findings support the premise that KAI1 functions
      as a tumor suppressor in this malignancy.

PMID- 15944769
TI  - Analysis of progressively overexpressed genes in tumorigenesis of colorectal
      cancers using cDNA microarray.
AB  - The identification of differentially expressed genes has important implications
      in understanding the biology of colorectal tumorigenesis and progression, as well
      as developing new diagnostic and therapeutic strategies. In this study, cDNA
      microarray technology was used to identify colorectal tumor-related functional
      genes, which are overexpressed continuously from colorectal adenoma to
      adenocarcinoma. A set of 23 genes with progressive overexpression in the
      development of colorectal cancer (CRC) was identified by cDNA microarray, then
      analyzed by sequencing and Northern blot analysis. Validation of our array
      results was simultaneously performed by exploring the SAGEmap database.
      Furthermore, the gradually over-expressed genes from adenoma to adenocarcinoma
      were validated by Northern blot analysis with additional samples from three
      patients with synchronous colorectal adenocarcinoma and adenoma and four patients
      with CRC. Of these 23 genes, one was a function-unknown gene, designated as Homo
      sapiens chromosome 21q22.1 anonymous mRNA sequence (Genbank accession no.
      AF003738), and 22 were function-known genes. Searching through the Gene Ontology
      Browser at the Cancer Genome Analysis Project website revealed that the
      biological roles of these 22 function-known genes are involved in cell motility,
      cell adhesion, chemokine activity, signal transduction, cytoskeleton
      organization, proteolysis, apoptosis, and cell proliferation. The genes
      identified in the present study offer valuable information on colorectal
      carcinogenesis and metastasis, and represent a potential source of novel targets
      for new strategies for CRC diagnosis and therapy.

PMID- 15944770
TI  - 5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and
      induce apoptosis through arachidonic acid pathway.
AB  - The metabolism of arachidonic acid by either the cyclooxygenase or lipoxygenase
      (LOX) pathway is believed to play an important role in tumor promotion. We
      investigated the expression of 5- and 12-LOX in renal cell carcinoma (RCC), as
      well as the effects of their inhibitors on cell proliferation in 2 RCC cell lines
      (Caki-1 and A498). Expression of 5- and 12-LOX was detected by
      immunohistochemistry and RT-PCR. Effects of LOX inhibitors on RCC cell growth
      were examined by MTT assay, and Hoechst staining was used to determine whether or
      not the LOX inhibitors induce apoptosis. While 5- and 12-LOX expression levels
      were slightly detected in NK tissues, marked expressions of 5- and 12-LOX were
      detected in RCC tissues. 5-LOX inhibitors caused marked reduction of RCC cells in
      a concentration- and time-dependent manner. The effect of the 5-LOX inhibitor was
      stronger than the 12-LOX inhibitor. Furthermore, the 5-LOX inhibitor caused a
      marked reduction of RCC cells through apoptosis. LOX, especially 5-LOX, is
      induced in RCC, and the results suggest that the 5-LOX inhibitor may mediate
      potent anti-proliferative effects against RCC cells. Thus, 5-LOX may become a new
      target in treatment of RCC.

PMID- 15944771
TI  - Microvascular density, vascular endothelial growth factor immunoreactivity in
      tumor cells, vessel diameter and intussusceptive microvascular growth in primary
      melanoma.
AB  - Intussusceptive microvascular growth (IMG) corresponds to one of the types of
      angiogenesis described in literature. Recent morphological work strongly supports
      a role for IMG, even during tumor angiogenesis. In this study, the extent of
      angiogenesis, evaluated as microvascular density, the immunoreactivity of tumor
      cells to vascular endothelial growth factor (VEGF), the vessel diameter and the
      IMG have been correlated to the tumor thickness in human primary melanoma
      specimens. Results showed that an increased microvascular density, a strong VEGF
      immunoreactivity of tumor cells, a major vessel diameter and a high number of
      connections of intraluminal tissue folds with the opposite vascular wall,
      expression of IMG, are correlated to a high tumor thickness (>3.6 mm). Overall,
      these data demonstrate for the first time in human primary melanoma a
      relationship between angiogenesis, VEGF immunoreactivity of tumor cells, vessels
      diameter and IMG and seem to indicate that VEGF is specifically involved in
      increasing vessel diameter and IMG.

PMID- 15944772
TI  - Structure-based assessment of BRCA1 and BRCA2 mutations in a small Spanish
      population.
AB  - Breast cancer is the most frequent cancer type among women in the world. There is
      abundant evidence, that alterations in the breast cancer susceptibility genes,
      BRCA1 and BRCA2, are present in a large proportion of families with multiple
      cases of breast and ovarian cancer. Our aim was to better understand the
      molecular and structural insights associated with the most frequent alterations,
      found in the BRCA1 and BRCA2 genes, within our patients. We analyzed 50 breast
      cancer cases. Of those, 24% were found to carry deleterious mutations, and up to
      10 rare variants of unknown significance were detected. The frequency of
      polymorphic changes was considerably different between genes, BRCA1 (55%) and
      BRCA2 (19.4%). By looking at the protein level, the changes observed within the
      BRCA1 and BRCA2 genes could affect not only the nucleic location of the protein
      but also disrupt the folding and, therefore, the tumor suppressor function.

PMID- 15944773
TI  - Loss of basement membrane heparan sulfate expression is associated with pelvic
      lymph node metastasis in invasive cervical cancer.
AB  - Perlecan is a major heparan sulfate proteoglycan of basement membrane (BM) and
      binds to various cytokines and growth factors via its heparan sulfate
      glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS
      GAG expression in invasive cervical cancers. We investigated the expression of BM
      HS-GAG by immunohistochemistry in 143 invasive cervical cancers and 30 metastatic
      lymph node samples, and analyzed correlations with various clinicopathological
      features. Furthermore, the gene expression levels of heparanase were assessed by
      RT-PCR in 52 invasive cervical cancer samples. HS-GAG expression index was
      significantly lower in cases of lymph node metastasis (p=0.01). There was no
      association between HS-GAG expression status and patient outcome. HS-GAG
      expression index in metastatic pelvic lymph nodes was significantly higher than
      that in the primary site (p=0.019). Furthermore, HS-GAG expression index was
      significantly lower in cases where heparanase mRNA expression was detectable
      (p=0.033). Heparanase mRNA expression is associated with the loss of BM HS-GAG
      expression, which is closely related to lymph node metastasis in invasive
      cervical cancers.

PMID- 15944774
TI  - Expression of insulin-like growth factor-I receptor, estrogen receptor alpha, Bcl
      2 and Bax proteins in human breast cancer.
AB  - Disturbance in expression of estrogen receptors together with changing influence
      of growth factor receptors and apoptosis associated proteins plays a role in
      breast cancer development and progression. However, immunohistochemical detection
      and relationships among these proteins were not often considered in relation to
      breast cancer and a few evaluations of expression provided mismatching results
      and conclusions. Consequently, we examined by immunohistochemistry the expression
      of the insulin-like growth factor-I receptor (IGF-IR), estrogen receptor alpha
      (ERalpha) and apoptosis-associated proteins, Bcl-2 and Bax, in human primary
      breast cancer, as well as analyzing the relationships among these proteins. The
      positive immunostaining for IGF-IR, ERalpha, Bcl-2 and Bax was noted in 56, 63.8,
      82.8 and 50% of tumors, respectively. We observed that IGF-IR negatively
      correlated with ERalpha in the group of all tumors and in axillary node negative
      cancer (p<0.03, p<0.05, respectively), but not in the subgroup of node positive
      cancer. Expression of ERalpha correlated positively with Bcl-2 and negatively
      with Bax proteins (p<0.0001, p<0.05, respectively). We did not note significant
      relationships between IGF-IR and Bcl-2, or IGF-IR and Bax proteins. We found that
      increased Bax expression was associated with positive lymph node status, pT2
      stage and G3 grade of tumors. Knowledge about alterations in the IGF-IR
      expression and relations of the receptor to other biological factors could help
      in our understanding of breast cancer biology and the importance of the IGF-IR in
      cancer progression as well as in effective management of breast cancer.

PMID- 15944775
TI  - Non-anti-coagulant heparin inhibits metastasis but not primary tumor growth.
AB  - Experimental and clinical studies indicate that low molecular weight heparins
      (LMWH) may inhibit cancer and/or metastasis. The purpose of this study was to
      investigate whether it is possible to design non-anti-coagulant, anti-metastatic
      compounds based on heparin. The LMWH Tinzaparin and a series of non-anti
      coagulant (NAC) heparin derivatives, varying in size from 2,500 to 10,000 Da,
      were tested for their anti-metastatic activity in an experimental B16F10
      metastasis model. The most promising NAC heparin drug candidate and Tinzaparin
      were further evaluated in B16F10 model with spontaneous metastasis from a primary
      subcutaneous tumor. In the experimental model, Tinzaparin, NAC2500, and NAC6000
      were inactive whereas both NAC8000 and NAC10000 significantly inhibited the
      number of induced experimental metastases by 69 and 73%, respectively. NAC8000
      was chosen over NAC10000 for further studies because of its lower molecular
      weight with an expected better bioavailability. In the spontaneous model,
      Tinzaparin had no inhibitory effect on metastatic activity. In contrast, NAC8000
      significantly inhibited the number of metastases by 58%. Neither Tinzaparin nor
      NAC8000 inhibited primary subcutaneous tumor growth. Together, these results
      indicate that the anti-metastatic effect of heparin derivatives is not a result
      of anti-coagulant activity. The non-anti-coagulant NAC8000 specifically inhibits
      early establishment of tumor cells, but not primary tumor growth. Therefore,
      NAC8000 is a promising non-anti-coagulant compound for preventing tumor
      metastasis.

PMID- 15944776
TI  - Urokinase-type plasminogen activator system and breast cancer (Review).
AB  - Malignant tumors have a capacity to degrade the extracellular matrix (ECM) by
      controlled proteolysis. One proteolytic system involved in these processes is the
      urokinase-type plasminogen activator (uPA) system, which consists of uPA, uPA
      receptor (uPAR) and uPA inhibitors 1 and 2 (PAI-1 and PAI-2). In the past two
      decades, study of the uPA system in human breast cancer has yielded valuable
      insights. Increased levels of uPA, PAI-1 and uPAR have been reported to be
      associated with poor prognosis in patients with breast cancer. Furthermore, uPA
      and PAI-1 may be new prognostic markers for axillary node-negative patients. To
      date, a growing body of evidence has suggested that uPA system promotes tumor
      metastasis by several different mechanisms, not just by breaking down the ECM.
      This article is focused on reviewing the current understanding of uPA system
      members as prognostic markers in breast cancer, and their cellular localization
      and tissue distribution. Correlations of the uPA system with other informative
      markers of breast cancer are also discussed.

PMID- 15944777
TI  - Flow cytometric analysis of circulating dendritic cell subsets and intracellular
      cytokine production in advanced breast cancer patients.
AB  - Patients with advanced cancer are known to have dysfunctions of the immune
      system. Dendritic cells (DCs) are potent antigen-presenting cells that play a
      crucial role in antitumor immune response. At least two peripheral blood DC
      subsets have been described: myeloid-derived CD11c+CD123- DCs (DC1) and lymphoid
      derived CD11c-CD123+ DCs (DC2). Upon interaction with T cells, DC2 seemed to
      support the generation of a Th2 response, while DC1 predominantly prime a Th1
      response. Our study was aimed at investigating the number of circulating DCs, and
      their subsets and functions in 32 patients with advanced breast cancer that
      achieved an objective response after a standard-dose sequential chemotherapy
      (CT), compared to 40 healthy controls. Circulating DC subsets and intracellular
      cytokine production in CD4+ and CD8+ subsets were analyzed using a tri-color flow
      cytometry assay. DC subsets were identified in peripheral blood, calculating
      their percentage gated as lin- HLA-DR+ and using BDCA-1, BDCA-2 and BDCA-3
      specific markers, as DC1 and DC2 according to expression of CD11c and CD123,
      respectively. Intracellular cytokines were evaluated in CD4+(Th1 and Th2) and
      CD8+ (Tc1 and Tc2) T lymphocytes. The mean percentage of BDCA-1+BDCA-2+BDCA-3 was
      similar to that of DC1+DC2 (p=ns). The mean percentage of DCs and DC1/DC2 ratio
      were slightly decreased before CT in cancer patients compared with healthy
      controls (p=ns). After CT, the percent-age of DC1 further decreased (p=0.02). The
      production of IFN-gamma (Th1 and Tc1) significantly decreased (p<0.03) while that
      of IL-4 (Th2 and Tc2) increased (p=0.04), thus confirming a shift toward a Th2
      CD4 and Tc2 CD8 phenotype and the predominance of type 2 DCs. Our results could
      help clarify the mechanisms of the immune response or immune status of patients
      with advanced breast cancer that undergo cytotoxic CT and contribute to improve
      the selection of potential candidates for active immunotherapy trials.

PMID- 15944778
TI  - Cellular kinetics and K-ras codon 12 mutations according to histomorphometric
      type of colorectal polyps with epithelial serrated proliferation.
AB  - Recent studies have examined cellular kinetics and genetic abnormalities in
      colorectal polyps with epithelial serrated proliferation (CP-ESP), including
      hyperplastic polyps, serrated adenomas, and tubulovillous adenomas. However,
      difficulty in histologically classifying these lesions and the lack of clear-cut
      diagnostic criteria have led to inconsistent findings. Some 60 cases of CP-ESP
      and 6 cases of CP-ESP with malignant transformation were studied. When nuclear
      size progressively decreased from the bottom and middle layers to the surface
      layer of the crypts, maturation gradient was considered positive. CP-ESP and CP
      ESP adjacent to carcinoma were morphologically classified as being positive or
      negative for maturation gradient and inferior and lateral glandular branching.
      Cellular kinetics were evaluated using Ki-67 immunostaining, and polymerase chain
      reaction (PCR)-dependent preferential homoduplex formation assay was performed to
      detect the presence or absence of K-ras codon 12-point mutations. CP-ESPs were
      morphologically classified into five types. In CP-ESP of types 1 to 4, the
      proliferation zone was confined to the bottom layer of the crypts or extended
      from the bottom to middle layers. In contrast, the proliferation zone extended
      throughout the crypts in most type 5 lesions. K-ras codon 12 mutations were
      detected in only types 3 and 5 CP-ESP. The five histomorphologic types of CP-ESP
      have distinct patterns of cellular kinetics. Histomorphologically, type 3 CP-ESP
      is considered an atypical hyperplastic polyp, occasionally associated with an
      elongated proliferation zone or K-ras mutations. Preliminary evidence indicates
      some relation between K-ras mutations and structural atypia associated with
      lateral branching of the crypts.

PMID- 15944779
TI  - A multicenter randomized study comparing 5-fluorouracil continuous infusion (ci)
      plus 1-hexylcarbamoyl-5-fluorouracil and 5-FU ci alone in colorectal cancer.
AB  - To verify the effectiveness of oral 1-hexylcarbamoyl-5-fluorouracil (HCFU) in
      improving the surgical cure rate in advanced colorectal cancer, a multicenter
      randomized comparative study was conducted. A total of 429 patients who had had
      curative resection for stage II and III colorectal cancer were randomly assigned
      to a study group receiving a 14-day course of 5-FU continuous infusion (320
      mg/m2/day) followed by oral HCFU for a year (300 mg/day), or to the control group
      receiving a 14-day course of 5-FU continuous infusion alone. In terms of
      background factors, no significant differences were found between the 214
      patients in the study group and the 215 in the control group. Adverse reactions
      during the treatment were more frequently seen in the study group. But with few
      exceptions, the toxicities were mild and the compliance was acceptable. The 5
      year overall survival rate of the study group was similar to that of the control
      group. The 5-year disease-free survival rate of the study group was better than
      that of the control group in the patients with colon cancer (hazard ratio=1.87;
      95% confidence interval 1.03-3.38; p=0.037). However, this benefit was not seen
      in the patients with rectal cancer. A significant improvement in the disease-free
      survival rate was demonstrated through the addition of HCFU to 5-FU continuous
      infusion for the patients with colon cancer. The usefulness of oral
      fluoropyrimidine as an adjuvant for curative surgery for colon cancer was further
      warranted.

PMID- 15944780
TI  - Chemotherapy under cachectic conditions and the possibility of cachexia
      controlled chemotherapy.
AB  - We studied the role of chemotherapy in cancer cachexia, which is well known to
      lower QOL and responsiveness to chemotherapy. In BALB/c mice we used two clones
      derived from the murine colon 26 adenocarcinoma cell line; clone 5, a non
      cachexigenic tumor and clone 20, a cachexigenic tumor, in which IL-6 mRNA was
      selectively detected. While maximum tolerated dose (MTD) of CPM and CPT-11 showed
      significantly smaller tumor weight and higher survival than 1/2 MTD in both drug
      groups with clone 5, the results were reversed with clone 20. The tumor weights
      with MTD of CPM or CPT-11 in combination with anti-IL-6 antibody treatment, which
      decreases serum IL-6 level and improves cachexia status, were significantly
      smaller than those in the MTD treatment-alone group with clone 20, but not with
      clone 5. From these results, we suggest that lower dose chemotherapy or cachexia
      controlled chemotherapy, such as some chemotherapeutic agents with neutralizing
      cachexia-related cytokine effects, elicit anti-tumor effects in cachectic
      individuals that are superior to conventional MTD chemotherapy.

PMID- 15944781
TI  - K252a inhibits proliferation of ovarian cancer cells by upregulating p21WAF1.
AB  - The furanosylated indolocarbazole, K252a, belongs to a family of microbial
      alkaloids that also includes staurosporine, which is known to inhibit
      proliferation, stimulate apoptosis and induce cell cycle arrest of cancer cells.
      To elucidate the involvement of K252a in ovarian cancer, we investigated the
      effects of K252a on the ovarian cancer cell line, SK-OV-3. SK-OV-3 cells were
      treated with K252a, and its effect on cell growth, cell cycle, and related
      measurements was assessed. MTT assays showed that the ovarian cancer cell line SK
      OV-3 cells were sensitive to the growth inhibitory effect of K252a. Cell cycle
      analysis indicated that their exposure to K252a decreased the proportion of cells
      in the S-phase and increased the proportion of cells in the G0/G1 phase of the
      cell cycle. This occurred in concert with altered expression of p21WAF1 protein
      related to the G0/G1 phase of the cell cycle. These results raise the possibility
      that K252a may prove particularly effective in treatment of ovarian cancer.

PMID- 15944782
TI  - Induction of S phase cell arrest and caspase activation by polysaccharide peptide
      isolated from Coriolus versicolor enhanced the cell cycle dependent activity and
      apoptotic cell death of doxorubicin and etoposide, but not cytarabine in HL-60
      cells.
AB  - Activation of the cell death program (apoptosis) is a strategy for the treatment
      of human cancer, and unfortunately a large number of drugs identified as cell
      cycle-specific agents for killing cancer cells are also toxic to normal cells.
      The present study demonstrates that the polysaccharide peptide (PSP) extracted
      from the Chinese medicinal mushroom, Coriolus versicolor, used in combination
      therapy in China, has the ability to lower the cytotoxicity of certain anti
      leukemic drugs via their interaction with cell cycle-dependent and apoptotic
      pathways. Flow cytometry analysis demonstrated that pre-treatment of PSP (25-100
      microg/ml) dose-dependently enhanced the cell cycle perturbation and apoptotic
      activity of doxorubicin (Doxo) and etoposide (VP-16), but not cytarabine (Ara-C)
      in human promyelocytic leukemia HL-60 cells. The antagonistic result from
      combined treatment with Ara-C and PSP may be caused by the removal of HL-60 cells
      in the G1-S boundary by PSP before exposure to Ara-C. A negative correlation
      between the increase in apoptotic cell population (pre-G1 peak) with the S-phase
      cell population expression (R2=0.998), the expression of cyclin E expression
      (R2=0.872) and caspase 3 activity (R2=0.997) suggests that PSP enhanced the
      apoptotic machinery of Doxo and VP-16 in a cell cycle-dependent manner and is
      mediated, at least in part, by the PSP-mediated modulation of the regulatory
      checkpoint cyclin E and caspase 3. This study is the first to describe the cell
      cycle mechanistic action of PSP and its interaction with other anticancer agents.
      Our data support the potential development of PSP as an adjuvant for leukemia
      treatment, but also imply the importance of understanding its interaction with
      individual anticancer agents.

PMID- 15944783
TI  - Inhibitory effect of glycolipids from spinach on in vitro and ex vivo
      angiogenesis.
AB  - Anti-cancer activity of some glycolipids from animals and plants has been
      demonstrated, although it was unknown whether the glycolipids had anti-angiogenic
      activity. The effects of the purified three glycolipids, monogalactosyl
      diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), and sulfoquinovosyl
      diacylglycerol (SQDG) from the green vegetable spinach (Spinacia oleracea L.)
      were examined on in vitro and ex vivo angiogenesis models. MGDG and SQDG
      suppressed microvessel growth in an ex vivo angiogenesis model using a rat aortic
      ring. The glycolipids inhibited human umbilical vein endothelial cell (HVUEC)
      tube formation on a reconstituted basement membrane and HUVEC proliferation.
      These results demonstrate that glycolipids from spinach would suppress tumor
      growth by suppressing angiogenesis and might be candidates for anti-cancer or
      anti-angiogenic materials.

PMID- 15944784
TI  - Expression of nerve growth factor receptors and their prognostic value in human
      pancreatic cancer.
AB  - Nerve growth factor (NGF), the prototypic member of the neurotrophin family of
      growth factors, exerts both stimulatory and inhibitory effects on neuronal and
      certain non-neuronal tumors, depending on the type of tumor. It has been reported
      that two types of NGF receptors, high-affinity receptor, TrkA, and low-affinity
      receptor, p75NGFR, play important roles in this process. Moreover, it has also
      been detected that high levels of TrkA expression have a more favorable overall
      survival prognosis in breast cancer patients, but the relationships between the
      two receptors according to the prognosis in pancreatic cancer patients are
      unknown. We investigated the expression of NGF receptors (NGFRs: TrkA and
      p75NGFR) mRNA in 56 human primary pancreatic cancers, using real-time
      quantitative reverse transcription-PCR. Moreover, pancreatic cancer cell lines
      were used to validate if the effects of NGF on pancreatic cancer cell growth are
      dependent on the expression levels and the balance of TrkA and P75 receptors.
      NGFRs were found in all of the tumor specimens and cell lines. It appears that in
      pancreatic cancer cells the growth effects of NGF depend on the expression levels
      and the ratio of TrkA and p75NGFR. TrkA and p75NGFR negatively correlated and
      were both associated with abdominal or back pain and perineural invasion.
      Regarding this, high TrkA expression levels exhibited more frequent perineural
      invasion and a higher degree of pain, whereas the results of p75NGFR are on the
      contrary. For Cox univariate analyses in the OS study, high expression of p75NGFR
      was associated with longer overall survival yet TrkA exhibited opposite effects
      and included the effect of pain. HPG, tumor size, node involvement, and
      perineural invasion were not prognostic factors. In Cox multivariate analyses,
      TrkA and p75NGFR were both prognostic para-meters. In conclusion, our study found
      that the expression of TrkA in pancreatic cancer is a marker of tumor
      aggressiveness. Conversely, we also found that elevated p75NGFR expression is
      associated with a favorable prognosis; we demonstrated that NGF exerts both
      stimulatory and inhibitory effects on pancreatic cancers with the effect based on
      the expression levels and the ratio of TrkA and p75NGFR.

PMID- 15944785
TI  - Occult neoplastic cells and malignant micro-aggregates in lymph node sinuses:
      review and hypothesis.
AB  - Many studies have shown a close relationship between the detection of occult
      neoplastic cells (ONCs) freely floating in lymph node sinuses remote from the
      primary tumor and the recurrence/metastasis of various malignancies. If 5 to 10
      circulating ONCs form an aggregate of tumor cells, it may easily escape attack by
      the host immune system. Since such malignant micro-aggregates cannot pass through
      the circulation in the liver and lungs, which filter tumor cells from the blood,
      the aggregates may become anchored in these organs and cause metastasis. A
      hypothesis is proposed that the most important factor leading to distant
      metastasis/recurrence of stage I or II cancer without microscopic lymph node
      metastasis, so-called N0 local disease (N0-LD), is the release of malignant micro
      aggregates consisting of many ONCs from the primary tumor. Distant
      metastasis/recurrence of N0-LD may occur when such infiltrating/proliferating
      cells enter target organs, especially the liver and lungs, in a viable state
      during their first pass through the circulation preoperatively and/or
      intraoperatively.

PMID- 15944786
TI  - Combination of 5-deoxy-5-fluorouridine and tamoxifen show cell-type specific
      antagonistic and cooperative effects on cytotoxicity in human mammary carcinoma
      cells.
AB  - The effect of tamoxifen (Tam) and 5-deoxy-5-fluorouridine (5-DFUR) cotreatment on
      cytotoxicity was assessed in various cancer-derived cell lines. Each cell line
      was treated with a range of Tam and 5-DFUR concentrations alone and in
      combination. The cell lines we examined include MDA-MB-231 (ERalpha-/ERbeta+),
      T47D (ERalpha+/ERbeta+), and three MCF-7 (ERalpha+/ERbeta+) sublines. Cell growth
      was assessed by MTT assay at multiple time points for up to 9 days. Fluorescence
      associated cell sorting (FACS) analysis was used to examine the effects of Tam
      and 5-DFUR cotreatment on cell cycle progression. Treatment with Tam or 5-DFUR,
      which is metabolized to 5-FU in target cells, produced an anti-proliferative
      effect that was dose- and time-dependent in all cell lines examined; variation in
      cell line sensitivity to each compound and cotreatment was apparent. When 5-DFUR
      and Tam treatment were combined, T47D, MDA-MB-231, and an MCF-7 subline
      demonstrated a cooperative effect at the lowest Tam concentration tested in 9-day
      cultures. The significance of treatment dosage and duration was obvious when 5
      DFUR and Tam cotreatment was observed to be antagonistic in 3-day cultures of a
      second MCF-7 subline and T47D cells. Results from our studies show that there may
      be cytotoxic benefits in the treatment of cancer from combined therapy with Tam
      and 5-FU precursor drugs. Enhanced inhibition of proliferation was observed when
      Tam was cotreated at low concentrations in relatively long-term cultures. This
      has clinical relevance in that it suggests that patients undergoing chemo
      endocrine therapy with orally administered 5-FU precursor drugs may benefit from
      lower treatment dosages relative to other adjuvant therapies.

PMID- 15944787
TI  - Polymorphism of the MUC1 mucin gene is associated with susceptibility to lung
      adenocarcinoma and poor prognosis.
AB  - MUC1 is a highly glycosylated glycoprotein that is often overexpressed in
      adenocarcinomas. MUC1 has molecular diversity because of a variable number of
      tandem repeats (from 25-125 repeats) in the extracellular domain of its core
      protein. MUC1 plays an important role in facilitating invasion and metastasis of
      malignant cells, and it also inhibits anti-cancer immune activity against
      malignant cells. We hypothesize that MUC1 allele length polymorphism (variable
      number of tandem repeats) is associated with development of lung adenocarcinoma.
      We evaluated MUC1 gene polymorphism using Southern blot analysis of peripheral
      blood from patients with non-small cell lung cancer (n=56), patients with benign
      respiratory disease (n=52), and healthy volunteers (n=52). We found that large
      MUC1 allele length was significantly associated with lung adenocarcinoma but not
      with squamous cell carcinoma of the lung. Adenocarcinoma patients with a
      homozygous large MUC1 genotype had a worse prognosis than patients with a
      heterozygous (large + small) MUC1 genotype or a homozygous small MUC1 genotype.
      These results suggest that the large MUC1 allele is associated with
      susceptibility to lung adenocarcinoma and poor prognosis.

PMID- 15944788
TI  - Methylation of the MLH1 gene in hematological malignancies.
AB  - Hypermethylation of the MLH1 gene has been described in many kinds of human
      cancers with microsatellite instability (MSI). However, it is not clear whether
      the same mechanism occurs in hematological malignancies. Genomic DNA was
      extracted from 31 patients with adult T-cell leukemia/lymphoma (ATL), 9 patients
      with acute lymphoblastic leukemia (ALL) who had MSI, and 12 leukemia and lymphoma
      cell lines with MSI. Aberrant methylation of the MLH1 gene was found in 2/31 (6%)
      ATL patients, and in 1/12 (8%) cell lines with MSI. MLH1 promoter was not
      methylated in either of the twelve peripheral blood samples from normal
      individuals or ALL samples. The MLH1 gene was expressed in the normal peripheral
      blood samples, but not in the MLH1-methylated cell line KCL22. Demethylation with
      5-Azacytidine treatment restored MLH1 expression in the KCL22 cell line.
      Methylation of the MSH2 gene was not found in any of the samples. Our data show
      that hypermethylation of the MLH1 gene is occasionally involved in the
      pathogenesis of hematological malignancies, but is not always associated with
      MSI.

PMID- 15944789
TI  - The extending range of the tumor is a more suitable predictive risk factor for
      lymph node metastases than the location of the deepest tumor invasion in distal
      thoracic esophageal and cardiac cancer.
AB  - In the regional lymph node grouping of esophageal cancer by the Japanese Guide
      Line (the 9th edition), the location of the deepest tumor invasion has precedence
      in determination. In this study, we investigated the extending range of the tumor
      and the location of the deepest tumor invasion to ascertain which was the more
      important factor in predicting lymph node metastases. We examined 52 patients
      with distal thoracic esophageal and cardiac cancer who had undergone
      esophagectomy with three-field lymph node dis-section. Among the 52 patients, 16
      were found to be positive and 36 negative, for middle-upper mediastinum and
      cervical lymph node metastases, and the two groups were compared in terms of
      detailed parameters of the tumor's location. In the result, the distance from the
      esophagogastric junction (EGJ) to the proximal margin of the tumor was
      significantly longer in the metastatic group (p=0.005). In univariate logistic
      regression with this parameter as the independent variable, we obtained a
      statistically significant result (p=0.0115, odds ratio=1.041, 95% confidence
      interval=1.009-1.073, R2=0.1169). On the other hand, when the distance from the
      EGJ to the deepest portion of the tumor was used as the independent variable,
      p=0.0742, odds ratio=1.045, 95% confidence interval=0.996-1.096 and R2=0.0577.
      Multiple logistic regression was performed with these two parameters, and the
      distance from the EGJ to the proximal margin of the tumor was a more important
      factor than the distance from the EGJ to the deepest portion of the tumor
      (p=0.0553 vs. 0.9161). We concluded that the extending range of the tumor was a
      more suitable predictive risk factor of lymph node metastases than the location
      of the deepest tumor invasion in distal thoracic esophageal and cardiac cancer.
      We should seriously consider the extending range of the tumor in the regional
      lymph node grouping of the Japanese Guide Line.

PMID- 15944790
TI  - Evaluation of 5-fluorouracil applicability by multi-point collagen gel droplet
      embedded drug sensitivity test.
AB  - The drug sensitivity of tumor cells is one of key issues to explore
      individualized therapy for cancer patients. One of such methods is in vitro
      anticancer drug sensitivity test which is generally based on one drug
      concentration and contact time. In this study, 5-fluorouracil (5-FU) sensitivity
      of cancer cells from colorectal cancer patients was evaluated by collagen gel
      droplet embedded drug sensitivity test (CD-DST) under multiple drug
      concentrations and contact durations. Cancer cells from 19 patients were measured
      for 9 drug concentration/contact time conditions (cohort 1) and from 34 patients
      were measured for 2 drug concentration/contact time conditions (cohort 2) using
      CD-DST. There was not significant difference in growth inhibition rate for 1.0
      microg/ml for 24 h and 0.2 microg/ml for 120 h, which gives the same area under
      the curve (AUC) (p=0.832) in all 53 patients (cohort 1 and 2). In cohort 1, 9
      conditions were successfully measured in 18 of 19 cohort 1 patients (94.7%). The
      drug concentrations and growth inhibition rate approximated to logarithmic curve
      for all 3 contact times and 50% inhibitory concentration (IC50) values at 3
      contact times could be calculated in these 18 patients. Growth inhibition rate
      and AUC also approximated to logarithmic curve. These values varied several
      orders of magnitude among patients. In vitro antitumor effect of 5-FU depended on
      AUC in colorectal tumor and it might support the use of continuous infusion or
      oral therapy which generates significant AUC with manageable toxicity. Some
      patients demonstrating low 5-FU sensitivity could not be indicated for 5-FU based
      therapy, and non-5-FU therapy should be explored for them.

PMID- 15944791
TI  - Efficacy of platinum-based chemotherapy after cranial radiation in patients with
      brain metastasis from non-small cell lung cancer.
AB  - This study was conducted to assess the efficacy of systemic chemotherapy in
      patients with brain metastasis from non-small cell lung cancer. Sixty-three
      consecutive patients who were diagnosed as having non-small cell lung cancer
      (NSCLC) with synchronous brain metastasis (BM) and had not been previously
      treated were included in this study. After cranial radiation therapy (RT), all
      patients in 'the chemotherapy arm' (CTX) were treated with platinum-based
      combination chemotherapy, and best supportive care was selected for patients in
      'the no-chemotherapy arm' (no-CTX). Thirty-one of the 63 patients received
      systemic chemotherapy. The median age of all patients was 55 years. The
      performance status of all patients was ECOG grade 1-2. Twenty-two patients had a
      solitary brain metastasis, 37 patients had more than two masses, and 38 patients
      had extracranial metastatic lesions. In the CTX arm, a paclitaxel-based
      combination chemotherapy was administered in 38.7%, gemcitabine-based in 25.8%,
      and vinorelbine-based in 25.8% as the first-line chemotherapy. Seventeen patients
      were treated with a second-line chemotherapy, and paclitaxel plus gemcitabine was
      used in 8 patients. For the first-line and second-line chemotherapies,
      extracranial overall responses were 36 and 35%, the median response durations
      were 29.1 weeks (range: 9.1-58.1 weeks) and 30.4 weeks (range: 19.4-44.0 weeks),
      respectively. 'Progression of the extracranial lesion' (58.1%) was more frequent
      than an 'aggravation of neurologic status' (19.4%) for the pattern of treatment
      failure in the first-line chemotherapy. The causes of failure were identical in
      the second-line chemotherapy. The median survival of the CTX arm was longer than
      that of the no-CTX arm (58.1 vs. 19.0 weeks, p<0.001). Toxicity in the CTX arm
      was tolerable. The systemic chemotherapy showed an effectiveness to increase the
      survival of patients with BM from NSCLC, and extracranial progression was the
      main cause of chemotherapeutic failure, although consideration for non-randomized
      methods should be made in this study.

PMID- 15944792
TI  - Combination of copper-chelating agent, trientine, and methotrexate attenuates
      colorectal carcinoma development and angiogenesis in mice.
AB  - Recent studies have suggested that an anti-angiogenic agent could improve the
      inhibitory effects of standard chemotherapeutic drugs against tumor development.
      We previously reported that the clinically used copper-chelating agent, trientine
      dihydrochloride (trientine), exerted strong anti-angiogenic activity and
      inhibited tumor growth. The aim of the current study was to examine the combined
      effect of trientine and methotrexate on the development and angiogenesis of
      xenograft human colorectal carcinoma (CRC) cells at clinically comparable low
      doses. When used individually, both trientine and methotrexate significantly
      suppressed CRC development along with inhibition of neovascularization in the
      tumor. A combination regimen of trientine and methotrexate exerted the most
      potent tumoricidal effect and led to 'tumor dormancy.' The combination of these
      agents also resulted in a marked suppression of the angiogenic factors, in
      particular the vascular endothelial growth factor and interleukin-8, and an
      increase of apoptosis in the tumor. In vitro studies revealed that neither
      trientine nor methotrexate was cytotoxic for tumor cells. On the other hand, the
      endothelial cell proliferation and tubular formation were significantly
      suppressed by these agents. The combined treatment of trientine and methotrexate
      at clinically comparable low doses could inhibit CRC development and
      angiogenesis, as well as suppress the angiogenic factors. Because both agents are
      widely used in clinical practice, the combination regimen may represent a
      potential new strategy for CRC therapy in the future.

PMID- 15944793
TI  - Simple mucin-type cancer associated antigens are pre-cancerous biomarkers during
      1,2-dimethylhydrazine-induced rat colon carcinogenesis.
AB  - The simple mucin-type truncated O-glycans Tn (GalNAc-O-Ser/Thr) and sialyl-Tn
      (STn) antigens are useful diagnostic markers for human colon cancer. We herein
      report the characterization of 1,2-dimethylhidrazine (DMH)-induced colon cancer
      in rats as a new model for the study of aberrant O-glycosylation products during
      carcinogenesis. Evaluated by immunohistochemistry, both anti-Tn and anti-STn MAbs
      revealed no staining of normal colonic mucosa. On the contrary, Tn and STn were
      expressed by the first lesions detected following carcinogen administration
      (aberrant crypt foci), observing the most intense and uniform pattern in crypts
      with severe dysplasia. Adenocarcinomas with non-secreting components showed
      moderately and strong stain, but mucin-secreting carcinomas were mildly stained.
      The biochemical characterization of soluble Tn glycoproteins from ascitic fluids
      of rats with colon cancer revealed that Tn is bearing high molecular weight
      glycoproteins (containing sialic acid and/or GlcNAc and GalNAc), which migrated
      as two major components (one of approximately 220 kDa and other>500 kDa).
      Evaluated by CsCl gradient ultracentrifugation and perchloric acid precipitation,
      it was shown that Tn is carried for mucins. These results indicate that Tn and
      STn are pre-cancerous biomarkers in colon of rats treated with DMH. This model of
      rat colon cancer could be useful to study in vivo the temporal sequence of
      molecular events responsible for the deregulation of O-glycosylation pathways
      during colon carcinogenesis, and could contribute to improve the evaluation of
      diagnostic and therapeutic strategies based on the utilization of Tn and STn
      antigens.

PMID- 15944794
TI  - Differentially expressed genes associated with human lung cancer.
AB  - To investigate the gene expression of 9 cDNA clones generated by suppression
      subtraction hybridization (SSH), Northern blot analysis was performed on a panel
      of immortalized bronchial epithelial cell lines, lung cancer cell lines and
      normal human bronchial epithelial cells (HBEC). The clones were located on
      chromosomes 1q, 2q, 3p, 3q, 4q and 14q representing regions that are frequently
      affected by DNA imbalances as shown by comparative genomic hybridization (CGH).
      Two were unknown (H24, H103) whereas the others matched to the Pest-containing
      nuclear protein (H52), Rp11-767C1 gene (H134), the hypothetical gene AK025444
      (H238), Guanine nucleotide binding protein (G protein)/alpha inhibiting activity
      polypeptide 2 (H268), Laminin gamma 1 (Y45), the DEAD (Asp-Glu-Ala-Asp/His) box
      polypeptide 9 (Y162) and the heat shock 90 kDa protein 1, alpha (Y238). Northern
      blot results indicated that all of the studied clones showed differential up- or
      down-regulation in immortalized cells and lung cancer cell lines. Of those, clone
      Y238 representing HSP90alpha showed a clearly over-expressed transcript.
      Subsequently, semi-quantitative RT-PCR was used to further confirm the over
      expression of Y238, indicating that HSP90alpha was significantly over-represented
      in 49 primary lung tumors as compared to 14 normal lung samples (P<0.01). CGH
      showed that the majority of studied lung cancer cell lines (71.4%) carried an
      overrepresentation at 14q32 where HSP90alpha is located suggesting that it may be
      affected by DNA copy number changes. The further characterization of these clones
      will provide us with valuable information on its role in lung carcinogenesis and
      may help to develop new diagnostic or therapeutic targets for this lethal
      disease.

PMID- 15944795
TI  - Measurement of plasminogen activator system components in plasma and tumor tissue
      extracts obtained from patients with breast cancer: an EORTC Receptor and
      Biomarker Group collaboration.
AB  - The plasminogen activator (PA) system comprises the 2 serine proteases, urokinase
      PA (uPA) and tissue PA (tPA), the 2 serpin inhibitors, PAI-1 and PAI-2 and the
      uPA receptor (uPAR; CD87). High levels of uPA, PAI-1, uPA-PAI-1 complex and uPAR
      in breast cancer tissue are associated with poor prognosis, while high levels of
      tPA or PAI-2 correlate with good prognosis. In this study, pre-operative plasma
      levels of uPA, PAI-1, uPAR, tPA, uPA-PAI-1 complex, and tPA-PAI-1 complex were
      measured in patients with benign (n=103) and malignant breast disease (n=113) by
      immunoenzymatic assays (ELISA). While plasma antigen levels of uPA, PAI-1, uPA
      PAI-1 complex and uPAR were not significantly different in the 2 groups, antigen
      levels of tPA and tPA-PAI-1 complex were significantly higher in patients with
      breast carcinoma compared to the control group. In plasma from the breast cancer
      patients, uPA levels correlated weakly but significantly with those of tPA
      (r=0.20, p=0.035) and uPAR (r=0.208, p=0.028). tPA levels correlated strongly
      with tPA-PAI-1 complex (r=0.972, p=0.0001) while uPA-PAI-1 levels were
      significantly associated with PAI-1 levels (r=0.534, p<0.0001), tPA levels
      (r=0.348, p=0.0003) and tPA-PAI-1 levels (r=0.356, p=0.002). However, no
      significant correlation was found between plasma and tumor tissue levels of uPA,
      PAI-1, uPA-PAI-1 complex, tPA or tPA-PAI-1. Our findings indicate that
      determination of these factors in plasma do not reflect their concentration in
      tumor tissue. Therefore, measurement of PA components in blood cannot be
      recommended for assessing prognosis in breast cancer.

PMID- 15944796
TI  - Prognostic and predictive relevance of microsatellite instability in colorectal
      cancer.
AB  - Microsatellite instability (MSI) is the phenotypic hallmark of a deficient DNA
      mismatch-repair system, observed in 10-20% of sporadic colorectal cancers (CRC).
      Since the prognostic and predictive value of this genetic alteration has been
      assessed mainly in non-randomised, uncontrolled studies, we investigated the
      potential of MSI to predict patient survival and response to adjuvant
      chemotherapy in tumour specimens from a randomised trial of the Swiss Group for
      Clinical Cancer Research (SAKK) that tested the value of 5-fluorouracil/mitomycin
      adjuvant chemotherapy. MSI status was determined in matched normal and tumour
      tissue samples from 160 patients using a panel of 9 microsatellite markers. There
      was no correlation between high frequency MSI (MSI-H) and overall (OS) or disease
      free survival (DFS) in the untreated control group of patients (HR=1.13, p=0.80;
      and HR=0.89, p=0.81, respectively). Furthermore, MSI-H phenotype did not predict
      for a larger benefit of adjuvant chemotherapy on OS or DFS (HR=0.49, p=0.41;
      HR=0.49, p=0.41, respectively), making a potential value of this molecular marker
      as a predictive factor in CRC unlikely. Our data do not confirm the prognostic
      relevance of MSI-H status in colorectal cancer patients found in some other
      studies. In addition, microsatellite instability did not correlate with the
      extent of chemotherapy benefit, although we observed a statistically non
      significant favourable impact of 5-FU-based treatment in the MSI-H group compared
      to MSI-L/MSS patients. Larger prospective randomised trials are required to
      conclusively establish a potential clinical significance of MSI in colorectal
      cancer.

PMID- 15944797
TI  - Qualitative and quantitative analysis of angiogenetic factors in transitional
      cell bladder carcinoma: relationship with clinical course at 10 years follow-up.
AB  - Many authors have shown that tumor hypoxia exerts its own influence on malignant
      progression by inducing angiogenetic factors and new blood vessels inside and
      around the tumor. This event usually suggests a poor prognosis and/or aggressive
      tumor behavior. The objective of the present study is to compare molecular
      analysis of angiogenetic factors with microvessel density (MVD) in bladder
      carcinoma. Twenty-nine consecutive patients underwent transurethral or open
      surgery for bladder tumors. Neoplastic tissue samples, normal-appearing bladder
      mucosa and blood samples were taken from each patient. All the tissues underwent
      mRNA extraction and Northern blot analysis, marked with specific probes for
      inducible nitric oxide sinthase (iNOS), cyclo-oxygenase-2 (cox-2), vascular
      endothelial growth factor (VEGF) and were evaluated by gel-electrophoresis.
      Microvessel density, a quantitative analysis for neoangiogenesis, was also
      evaluated by using CD31 immunohistochemical assay and compared with both
      molecular analysis and patient follow-up. Two follow-up for recurrence and/or
      progression were performed at 74 months and 10 years from surgery respectively.
      Pathological evaluation demonstrated the presence of superficial transitional
      cell carcinoma (sTCC) in 15 patients, while 14 had an invasive bladder tumor
      (iBT). At both 74 months and 10 years follow-up, all patients with lower MVD had
      a shorter survival time. No significant results were obtained by comparing
      disease progression or survival rate with VEGF, iNOS and COX-2 levels. A
      proportional increase of VEGF expression and MVD compared with poor prognosis was
      the expected outcome of our study. These results were disregarded at both the 1st
      and the 2nd follow-up. A strong association between MVD>20 and survival rate was
      noted both in sTCC (p=0.024) and iBT (p>0.001) patients. These results confirm
      that MVD could be considered a good prognostic factor. The angiogenetic cytokines
      overexpression found in control tissue samples of sTCC could have clinical
      significance, either as a macroscopically unidentified diffuse carcinogenetic
      process or the presence of a systemic immune-response against tumor cells.

PMID- 15944798
TI  - Systemic inflammation correlates with increased expression of skeletal muscle
      ubiquitin but not uncoupling proteins in cancer cachexia.
AB  - Muscle wasting in experimental cancer cachexia has been associated with increased
      ubiquitin proteasome proteolytic system activity and increased uncoupling protein
      (UCP) expression. Increased ubiquitin proteasome pathway activity has also been
      found in gastric, but not lung, cancer patients. It therefore remains unclear in
      which patients modulation of this proteolytic system could be a therapeutic
      target. We investigated markers of systemic inflammation, hypermetabolism and
      expression of ubiquitin and uncoupling proteins 2 and 3 in muscle of pancreatic
      cancer patients. Rectus abdominis muscle was sampled from 15 weight-losing
      pancreatic cancer patients and 11 controls. UCP2 and 3, and ubiquitin mRNA
      expression were measured by Northern blots and UCP3 protein by Western blotting.
      Resting energy expenditure and plasma IL-6, sTNF-R and C-reactive protein (CRP)
      were also measured. Cancer patients had lost 18% of pre-illness stable weight,
      but were not significantly hypermetabolic compared with controls. IL-6, sTNF-R
      and CRP levels and ubiquitin 2.4 kb, but not 1.2 kb, mRNA expression were
      increased in cancer patients. UCP-2 and 3 mRNA and UCP-3 protein were similar in
      both groups. Weight loss correlated with systemic inflammation and ubiquitin 1.2
      and 2.4 kb mRNA expression. Weight loss in pancreatic cancer is associated with
      systemic inflammation and increased mRNA expression for ubiquitin but not
      uncoupling proteins in skeletal muscle. The pro-inflammatory network and
      ubiquitin proteasome pathway may be targets for intervention in pancreatic cancer
      cachexia.

PMID- 15944799
TI  - A high-fat diet enhances the inhibitory effect of dietary vitamin B6 on colon
      cell proliferation in mice.
AB  - Previously we reported that dietary supplemental vitamin B6 (B6) reduced colon
      tumorigenesis and cell proliferation in mice receiving azoxymethane (AOM) for 22
      weeks. This study was conducted to examine the influence of short-term
      consumption (5 weeks) of diets containing graded levels of B6 and fat on colonic
      cell proliferation in mice with or without receiving AOM. In experiment 1, mice
      were fed the 10% corn oil diet containing 1, 7, 14, 35 or 70 mg pyridoxine
      HCl/kg, and received weekly injections of AOM for the initial 3 weeks. In
      experiment 2, mice were fed 5 or 20% corn oil diet containing 1, 7, 14 or 35 mg
      pyridoxine HCl/kg, and received weekly injections of AOM or saline for the
      initial 3 weeks. In experiment 1, supplemental B6 caused a dose-dependent
      reduction of colon aberrant crypt foci and cell proliferation (BrdU-labeling
      index) among the 1-14 mg pyridoxine HCl/kg. There was no influence of B6 on these
      parameters among 14-70 mg pyridoxine HCl/kg. Immunohistochemical analysis of
      apoptosis labeling by TUNEL method indicated no influence of dietary B6 on colon
      apoptosis. In experiment 2, supplemental B6 significantly reduced colon cell
      proliferation regardless of AOM injection. This inhibitory effect on cell
      proliferation was markedly enhanced by a high-fat diet, but slightly affected by
      AOM treatment. The results suggest that dietary supplemental B6 inhibits colon
      cell proliferation from the early stage of colon carcinogenesis, and a high-fat
      diet markedly enhances the inhibitory effect.

PMID- 15944800
TI  - Human DNA topoisomerase II-alpha expression in laparoscopically treated renal
      cell carcinoma.
AB  - To investigate whether the expression of Topoisomerase II-alpha (TII-alpha) can
      serve as a prognostic factor in renal cell carcinoma (RCC), histological sections
      from 27 renal tumors were stained immunohistochemically for TII-alpha expression.
      The percentage of positive cells in the area of greatest staining was recorded as
      the TII-alpha index. TII-alpha nuclear staining was positive in all the samples
      except one. The mean TII-alpha index was 12.5 for grade 1, 44 for grade 2 and 113
      for grade 3 tumors. The mean TII-alpha index was 22.3 in tumors which did not
      recur and 81 for tumors which recurred during the follow-up period. In this
      study, a higher TII-alpha index correlated with more aggressive tumor behaviour.
      However, a large cohort of patients should be assessed before drawing definitive
      conclusions.

PMID- 15944801
TI  - Induction of apoptosis in human ovarian epithelial cancer cells by antisurvivin
      oligonucleotides.
AB  - Survivin, an anti-apoptosis gene that is abnormally overexpressed in a variety of
      human tumors, may play an important role in the carcinogenesis and drug
      resistance of cancer. This study was designed to explore the effects of liposome
      survivin antisense oligonucleotide (Lip-ASODN) on the growth and apoptosis of
      human ovarian cancer cell lines, A2780 and SKOV3. To investigate the use of
      survivin as a therapeutic target on ovarian cancer, we carried out transfections
      with Lip-ASODN to induce apoptosis in ovarian cancer cell lines, A2780 and SKOV3.
      The expression of survivin mRNA and relative protein were evaluated separately by
      quantitative real-time RT-PCR and Western blot analysis. Cell proliferation
      inhibition was determined by methyl thiazolyl tetrazolium (MTT) assay, and the
      induced cell apoptosis was examined using flow cytometry (FCM) after Lip-ASODN
      transfection. Our results showed that the overexpression of survivin led to
      infinite carcino-proliferation, and survivin expression in the survivin-positive
      ovarian cancer cell line A2780 and SKOV3 cells was significantly and gradually
      reduced when transfected with Lip-ASODN at concentrations of 200, 400 and 600 nM
      by degrees. Lip-ASODN transfection induced greater apoptosis rates in the human
      ovarian cancer cell lines A2780 and SKOV3 (p<0.05). The growth inhibition and
      apoptotic rates of tumor cells change when treated with different concentrations
      of Lip-ASODN. The cell growth inhibition peak rate was reached when increasing
      Lip-ASODN concentration to 600 nM. Furthermore, time course evaluation showed
      that survivin protein expression was inhibited by Lip-ASODN within 12 h after
      transfection. We concluded that down-regulation of survivin by a targeted
      antisense oligonucleotide appears to be an effective gene therapy approach in the
      treatment of ovarian cancer.

PMID- 15944802
TI  - Cisplatin sensitization by concurrent mild hyperthermia in parental and mutant
      cell lines deficient in homologous recombination and non-homologous endjoining
      repair.
AB  - The effect of mild hyperthermia on cisplatin sensitization was examined in two
      cell line pairs, CHO parental AA8 and irsISF, an XRCC3 mutant (deficient in
      homologous recombination repair), and mouse parental MEF and knockout Ku80
      mutants (deficient in non-homologous endjoining repair). The results showed that
      mild hyperthermia 40, 41 and 42 degrees C given concurrently with cisplatin
      treatment caused significant sensitization. The degree of sensitization was
      comparable for the parental and mutant lines, indicating that these repair
      pathways were likely not involved in cisplatin thermal sensitization. The shorter
      concurrent treatments cause a larger sensitization than the longer treatments.
      The reasons for this are not clear, but thermotolerance may be a factor.

PMID- 15944803
TI  - Comparative genomics on Fgf11 orthologs.
AB  - Human FGF19 is the ortholog of rodent Fgf15, and 22 FGF family genes exist within
      the human genome as well as within the rodent genome. Mouse Fgf11 refSeq
      NM_010198.1 and rat Fgf11 RefSeq NM_130816.1 correspond only to the coding
      region. Here, complete coding sequences of mouse, rat and dog Fgf11 orthologs
      were determined by using bioinformatics. Mouse Fgf11, rat Fgf11 and dog Fgf11
      genes, consisting of five exons, were located within AL603707.5, AC098923.8 and
      AC126237.5 genome sequences, respectively. Human FGF11 showed 97.8%, 96.9%, 96.9%
      and 68.9% total-amino-acid identity with dog, mouse, rat and zebrafish Fgf11
      orthologs, respectively. Rat Fgf11 showed Val205Met amino-acid substitution
      compared with rat Fgf11 RefSeq NP_570829.1. Met 205 of rat Fgf11 determined in
      this study was conserved among vertebrate Fgf11 orthologs. N-terminal signal
      peptide was not identified within vertebrate Fgf11 orthologs. Two Asn-linked
      glycosylation sites were identified within zebrafish fgf11, but not within
      mammalian Fgf11 orthologs. The 5'-flanking region, exonic regions, and intronic
      regions except intron 3 were well conserved between human FGF11 and mouse Fgf11
      genes. Match program revealed that EVI1, ELK1, AP1 and E47-binding sites were
      conserved between human FGF11 and mouse Fgf11 promoter regions. Human FGF11 mRNA
      was expressed in embryonic stem (ES) cells, neuroblastoma, retinoblastoma, and
      brain tumors. This is the first report on the dog Fgf11 gene as well as on
      comparative genomics analyses of Fgf11 orthologs.

PMID- 15944804
TI  - Comparative genomics on FGF20 orthologs.
AB  - We cloned and characterized human FGF20 in August, 2000. Ohmachi et al claimed
      the same gene as a novel FGF family member in October, 2000, and Jeffers et al in
      April, 2001. FGF20 is up-regulated in colorectal cancer due to the activation of
      WNT/beta-catenin pathway. FGF20 is applicable as the mucosal protective agent for
      inflammatory bowel disease and chemotherapy/radiation-induced oral mucositis, and
      also as the inducer of dopaminergic neurons for Parkinson's disease. FGF20 is a
      target of pharmacogenomics in the field of oncology and regenerative medicine.
      Here, comparative genomics analyses on FGF20 orthologs were performed. Zebrafish
      fgf20 gene, consisting of three exons, was located within BX323810.8 genome
      sequence. Zebrafish fgf20 (208 aa) showed 76.9%, 76.4%, 76.0% and 75.5% total
      amino-acid identity with human FGF20, Xenopus fgf20, rat Fgf20 and mouse Fgf20,
      respectively. Fgf20 orthologs were well conserved among vertebrates. Human FGF20
      gene was linked to EFHA2 gene in head-to-head manner with an interval of about 25
      kb. FGF20-EFHA2 locus at human chromosome 8p22 and FGF9-EFHA1 locus at human
      chromosome 13q12.11 were paralogous regions (paralogons) within the human genome.
      The 5'-flanking promoter region, exonic regions except 3'-UTR, and middle regions
      within intron 1 were conserved between human FGF20 and mouse Fgf20 genes. Double
      TCF/LEF binding sites, double EVI1-binding sites, TGIF, PAX4, E47 and AREB6
      binding sites were conserved between human FGF20 promoter and mouse Fgf20
      promoter.

PMID- 15944805
TI  - Xylanases from fungi: properties and industrial applications.
AB  - Xylan is the principal type of hemicellulose. It is a linear polymer of beta-D
      xylopyranosyl units linked by (1-4) glycosidic bonds. In nature, the
      polysaccharide backbone may be added to 4-O-methyl-alpha-D-glucuronopyranosyl
      units, acetyl groups, alpha-L-arabinofuranosyl, etc., in variable proportions. An
      enzymatic complex is responsible for the hydrolysis of xylan, but the main
      enzymes involved are endo-1,4-beta-xylanase and beta-xylosidase. These enzymes
      are produced by fungi, bacteria, yeast, marine algae, protozoans, snails,
      crustaceans, insect, seeds, etc., but the principal commercial source is
      filamentous fungi. Recently, there has been much industrial interest in xylan and
      its hydrolytic enzymatic complex, as a supplement in animal feed, for the
      manufacture of bread, food and drinks, textiles, bleaching of cellulose pulp,
      ethanol and xylitol production. This review describes some properties of xylan
      and its metabolism, as well as the biochemical properties of xylanases and their
      commercial applications.

PMID- 15944806
TI  - Intracoronary formation and retention of micro aggregates of leukocytes and
      platelets contribute to postischemic myocardial dysfunction.
AB  - OBJECTIVE: Cardiac pump function and coronary regulation can be impaired after
      short-term ischemia. Recent studies with platelets (P) and neutrophils (PMN)
      yielded contradicting results about the "cellular" contribution to reperfusion
      injury. METHODS: Isolated guinea pig hearts performing pressure-volume work were
      employed, external heart work (EHW), aortic flow (AF), coronary flow (CF) and
      heart rate (HR) serving as parameters of cardiac function. After global ischemia,
      human blood cells were given as bolus (1 min) during reperfusion (intracoronary
      hematocrit 7%). Expression of specific adhesion molecules (P: CD62P, CD41; PMN:
      integrin CD11b) was measured on cells before and after coronary passage (FACS
      analysis). RESULTS: Postischemic recovery of pump function was significantly
      reduced in hearts with blood cell application (EHW: -cells 54 +/- 14%, +cells 41
      +/-12%, p <0.05). Coronary response to bradykinin and reactive hyperemia were not
      effected. The blood-cell dependent functional loss was partly reduced by blocking
      CD18 (anti-CD 18) and completely abrogated by blockage of CD41 (lamifiban). The
      expression of CD11b on PMN and monocytes (M) and CD62P on platelets was
      significantly reduced in the coronary effluent and a significant decrease of CD41
      on leukocytes occurred during coronary passage after ischemia. Increases in CD41
      on PMN in the presence of lamifiban demasked intracoronary formation of micro
      aggregates (P/PMN). These micro aggregates were visualized by light microscopy.
      Electron microscopy revealed no significant microvascular plugging. CONCLUSION:
      1) A specifically blood-cell induced loss of myocardial pump function has been
      demonstrated after short-term ischemia. 2) CD41 (= GpIIbIIIa) on P is responsible
      for this cardiac reperfusion damage. 3) The effect is causally linked to the
      formation of micro aggregates between PMN and P, but seems attenuated in the
      presence of erythrocytes as compared to effects reported from experiments in
      which PMN and P were applied singly or co-perfused. 4) Intracoronary retention of
      PMN, M and platelet-leukocyte micro aggregates seems to be transient, as
      adherence was not confirmed by electron microscopy.

PMID- 15944807
TI  - Erythropoietin protects the myocardium against reperfusion injury in vitro and in
      vivo.
AB  - OBJECTIVE: Erythropoietin (EPO) is a hormone that is currently used to treat
      patients with renal failure and anaemia. However, it has also been shown to
      protect against ischaemia/reperfusion injury; this protection occurring via
      activation of the ERK 1/2 and PI3K pathways. Since we have previously shown
      activation of ERK 1/2 and PI3K to be important for protection against reperfusion
      induced injury in the myocardium, this study was designed to investigate its
      effect in the myocardium using both an isolated perfused rat heart and an in vivo
      rat recovery model of ischaemia-reperfusion. METHODS: Using an in vitro isolated
      rat heart model of 35 minutes ischaemia and 2 hours reperfusion, EPO (50 ng/ml)
      was administered to the rat myocardium 5 minutes prior to reperfusion for 20
      minutes. The in vivo open-chest rat model consisted of 40 minutes ischaemia
      followed by 24 hours reperfusion with EPO (5000 U/kg) being administered at the
      point of reperfusion. RESULTS: In the isolated perfused heart studies 50 ng/ml
      EPO was found to provide protection with a % I/R of 22.9% +/- 6.4 vs 54.5% +/-
      7.4 for the ischaemic control group. To examine the mechanistic pathways involved
      in EPO-mediated protection, we co-administered the ERK 1/2 inhibitor, U0126 (10
      uM) or the PI3K inhibitors, wortmannin, (100 nM) and LY294002 (15 microM) at
      reperfusion. U0126, wortmannin and LY294002 all abrogated EPO-mediated protection
      (% I/R 49.2% +/- 5.6, 46.1% +/- 5.5 and 49.9% +/- 6.1 respectively, p < 0.05). In
      the in vivo open-chest rat model, the % I/R was significantly attenuated in EPO
      treated animals from 53.6 % +/- 3.7 in the control to 32.5% +/- 2.9 (p < 0.05).
      Likewise, wortmannin abrogated EPO-mediated protection (% I/R 50.7 +/- 2.3 v EPO
      32.5% +/- 2.9, p < 0.05). CONCLUSION: We demonstrate that EPO, administered at
      the point of reperfusion, reduced infarct size in an isolated perfused rat heart,
      in an ERK and PI3K dependent manner; in addition the mechanism was also confirmed
      in a whole animal model of ischaemia-reperfusion. These results suggest that EPO
      may be able to directly protect the myocardium against lethal reperfusion-induced
      injury and so offer the myocardium an additional clinical advantage over and
      above its ability to improve the oxygen carrying capacity of the blood.

PMID- 15944808
TI  - Influence of obstructive sleep apnea on heart rate turbulence.
AB  - BACKGROUND: Patients with obstructive sleep apnea (OSA) are at increased risk for
      cardiovascular disease. Increased sympathetic drive is considered as one of the
      underlying mechanisms. Both heart rate turbulence (HRT) and heart rate
      variability (HRV) are parameters to describe autonomic regulation. We
      investigated the influence of sleep-disordered breathing (SDB) on HRT and HRV in
      patients with OSA. METHODS: Sixty-five patients underwent overnight
      polysomnography for clinically suspected SDB and simultaneous Holter monitoring
      (11 p.m.-6 a.m.). Patients with diabetes mellitus, a history of cardiac disease,
      left ventricular dysfunction, periodic breathing pattern, and those on beta
      blockers or theophylline were excluded. According to the apnea-hypopnea index
      (AHI), the patients were assigned to group A (AHI <20, n = 31) or group B (AHI >
      or =20, n = 34). HRV (time domain, frequency domain) and HRT (onset, slope) were
      then related to the severity of SDB. RESULTS: Nighttime turbulence slope (TS)
      correlated inversely with the AHI (r = -0.45, p = 0.01) and was significantly
      lower in group B (8.9 +/- 1.6 ms/R-R interval) compared with that in group A
      (19.8 +/- 4.0 ms/R-R interval, P = 0.01). This relationship remained stable after
      adjusting TS for the number of ventricular premature contractions. No significant
      differences in turbulence onset or parameters of nighttime HRV were observed.
      CONCLUSIONS: Alterations in nighttime HRT correlate with the severity of SDB,
      indicating abnormalities in cardiac autonomic activity in moderate-to-severe OSA
      even in the absence of overt cardiac disease. These changes may be associated
      with the subsequent development of cardiovascular disease.

PMID- 15944809
TI  - Verapamil prevents torsade de pointes by reduction of transmural dispersion of
      repolarization and suppression of early afterdepolarizations in an intact heart
      model of LQT3.
AB  - BACKGROUND: In long QT syndrome (LQTS), prolongation of the QT-interval is
      associated with sudden cardiac death resulting from potentially life-threatening
      polymorphic tachycardia of the torsade de pointes (TdP) type. Experimental as
      well as clinical reports support the hypothesis that calcium channel blockers
      such as verapamil may be an appropriate therapeutic approach in LQTS. We
      investigated the electrophysiologic mechanism by which verapamil suppresses TdP,
      in a recently developed intact heart model of LQT3. METHODS AND RESULTS: In 8
      Langendorff-perfused rabbit hearts, veratridine (0.1 microM), an inhibitor of
      sodium channel inactivation, led to a marked increase in QT-interval and
      simultaneously recorded monophasic ventricular action potentials (MAPs) (p <
      0.05) thereby mimicking LQT3. In bradycardic (AV-blocked) hearts, simultaneous
      recording of up to eight epi- and endocardial MAPs demonstrated a significant
      increase in total dispersion of repolarization (56%, p < 0.05) and reverse
      frequency-dependence. After lowering potassium concentration, veratridine
      reproducibly led to early afterdepolarizations (EADs) and TdP in 6 of 8 (75%)
      hearts. Additional infusion of verapamil (0.75 microM) suppressed EADs and
      consecutively TdP in all hearts. Verapamil significantly shortened endocardial
      but not epicardial MAPs which resulted in significant reduction of ventricular
      transmural dispersion of repolarization. CONCLUSIONS: Verapamil is highly
      effective in preventing TdP via shortening of endocardial MAPs, reduction of left
      ventricular transmural dispersion of repolarization and suppression of EADs in an
      intact heart model of LQT3. These data suggest a possible therapeutic role of
      verapamil in the treatment of LQT3 patients.

PMID- 15944810
TI  - Parathyroid hormone-related peptide improves contractile responsiveness of adult
      rat cardiomyocytes with depressed cell function irrespectively of oxidative
      inhibition.
AB  - Parathyroid hormone-related peptide (PTHrP) was found to improve contractile
      function of stunned myocardium in pigs. The peptide is released from coronary
      endothelial cells during ischemia and significantly improves post-ischemic
      recovery. The present study was aimed to decide whether such an induction of
      contractile responsiveness of the heart requires co-activation of adjacent cells
      or is a genuine phenomenon of cardiomyocytes. A second aim of this study was to
      decide whether such an improvement is linked to depressed cell function in
      general or oxidative inhibition. Isolated adult ventricular cardiomyocytes from
      rats were constantly paced at 0.5 Hz for 10 min. Cells were exposed to a brief
      oxidative inhibition by addition of 0.5 mmol/l potassium cyanide (KCN) in the
      presence of glucose. Under these conditions, cells stopped beating after 280 s on
      average. 30 s before they stopped to beat, cells had already developed a
      reduction in cell shortening, maximal relaxation and contraction velocity. In the
      co-presence of PTHrP (1-34) (100 nmol/l) cells continued to beat regular and did
      not develop reduced cell shortening, irrespectively of oxidative inhibition. In a
      second attempt, cells were exposed to the NO donor SNAP (100 micromol/l) or 8
      bromocGMP (1 mmol/l). As expected both agents reduced cell shortening
      significantly. This reduction in cell shortening was attenuated in co-presence of
      PTHrP, too. Finally, we investigated the effect of PTHrP on cell shortening at
      different extracellular concentrations of calcium. Although, PTHrP increased
      intracellular calcium at 2 and 5 mmol/l extracellular calcium, respectively, it
      improved cell shortening only at 5 mmol/l extracellular calcium. Thus, the
      beneficial effect of PTHrP on cell shortening was independent from intracellular
      calcium but dependent on the steepness of the calcium gradient between intra- and
      extracellular calcium. In conclusion, our study shows that PTHrP is able to
      improve cell shortening rapidly and directly irrespectively of the reason for the
      reduced cell function. Improved electromechanical coupling rather than
      intracellular calcium handling seems to be the most important mechanism.

PMID- 15944811
TI  - Timing of aneurysm surgery in subarachnoid haemorrhage--an observational study in
      The Netherlands.
AB  - BACKGROUND: There is still lack of evidence on the optimal timing of surgery in
      patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical
      trial has been done, which showed no difference between early and late surgery.
      Other studies were observational in nature and most had methodological drawbacks
      that preclude clinically meaningful conclusions. We performed a retrospective
      observational study on the timing of aneurysm surgery in The Netherlands over a
      two-year period. METHOD: In eight hospitals we identified 1,500 patients with an
      aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion
      criteria. We included all patients who were admitted and were conscious at any
      one time between admission and the end of the third day after the haemorrhage. We
      categorised the clinical condition on admission according the World Federation of
      Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as
      operation performed within three days after onset of subarachnoid haemorrhage;
      intermediate surgery as performed on days four to seven, and late surgery as
      performed after day seven. Outcome was classified as the proportion of patients
      with poor outcome (death or dependent) two to four months after onset of
      subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as
      reference. We distinguished between management results (reconstructed intention
      to treat analysis) and surgical results (on treatment analysis). The results were
      adjusted for the major prognosticators for outcome after subarachnoid
      haemorrhage. FINDINGS: We included 411 patients. There were 276 patients in the
      early surgery group, 36 in the intermediate surgery group and 99 in the late
      surgery group. On admission 78% were in good neurological condition (WFNS I-III).
      MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor
      outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late
      surgery group had a poor outcome. For patients in good clinical condition on
      admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95%
      CI 0.5 to 3.0). The adjusted OR for patients admitted in poor
      neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI
      0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on
      admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to
      3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical
      condition. CONCLUSIONS: In this observational study we found no significant
      difference in outcome between early and late operation for patients in good
      clinical condition on admission. For patients in poor clinical condition on
      admission outcome was significantly better after early surgery. The optimal
      timing of surgery is not yet settled. Ideally, evidence on this issue should come
      from a randomised clinical trial. However, such a trial or even a prospective
      study are unlikely to be ever performed because of the rapid development of
      endovascular coiling.

PMID- 15944812
TI  - Central European Neurosurgical Society (CENS)--history and the third meeting.

PMID- 15944813
TI  - Serpinopathy and endoplasmic reticulum stress.
AB  - We have recently identified a novel human gene, megsin, which is a new serine
      protease inhibitor (serpin) predominantly expressed in the kidney. Our previous
      studies suggested a role of megsin in the pathogenesis of human renal diseases,
      but its exact biopathological significance remained unknown. During the analysis
      of experimental animals overexpressing the human megsin gene, we unexpectedly
      generated a "serpinopathy" model involving the kidney and pancreas and discovered
      a novel mechanism of renal injury, that is, cellular damage by endoplasmic
      reticulum (ER) stress caused by conformational disorder of protein tertiary
      structure within the ER. In vitro induction of ER stress may play a role in renal
      cell injury by various stimuli, but the involvement of ER stress in human renal
      disease remains elusive. Further research for ER structure and function may open
      new exciting prospects in the pathology of human renal diseases.

PMID- 15944814
TI  - A mammalian dpy-19 homologue is expressed in GABAergic neurons.
AB  - Gsh2 homeobox transcription factors play a crucial role in the development of
      GABAergic neurons. Caenorhabditis elegans's mab-5 gene is homologous to Gsh2; its
      expression is controlled by dpy-19. This study produced the polyclonal anti
      mammalian DPY-19 (MDPY-19) antibody and showed the distribution of anti-MDPY-19
      immunopositive cells. In addition, the mammalian dpy-19 (Mdpy-19) 5'-flanking
      region was analyzed by in vivo transient transfection assays. Mdpy-19 is
      expressed in ependymal cells in the adult rat brain, embryonic neuroepithelial
      cells, and cultured neural stem cells. In the adult rat ventricular zone,
      immunoreactivity with MDPY-19 of the dorsal area is stronger than that of the
      ventral area. Embryonic neuroepithelial cells and radial glial cells show strong
      anti-MDPY-19 immunoreactivity. We created the Mdpy-19 green fluorescent protein
      (GFP) reporter gene. Our results show that Mdpy-19 is expressed in neural stem
      cells and progenitor cells, especially radial glial cells. Only ependymal cells
      among differentiated cells express Mdpy-19 gene. However, the possibility exists
      that the Mdpy-19 gene is able to transcript in GABAergic neurons. It is suggested
      that a factor existing in mature neurons withdraws the expression of Mdpy-19.

PMID- 15944815
TI  - O-GlcNAc modification of nucleocytoplasmic proteins and diabetes.
AB  - Nuclear and cytosolic proteins are glycosylated on serine or threonine residues
      by O-linked beta-N-acetylglucosamine (O-GlcNAc). O-GlcNAc modification is one of
      various posttranslational modifications and seems to be involved in the
      modulation of transcription and signal transduction. Accumulating data suggest a
      role for O-GlcNAc-modified proteins in diabetes, acting as a glucose sensor. It
      has been suggested that the hexosamine biosynthetic pathway is involved in the
      mechanism causing insulin resistance and diabetic complications. Excess glucose
      entering into the hexosamine biosynthetic pathway might cause elevated O-GlcNAc
      modification of various proteins. In this article, we review the current data
      regarding the relationship between O-GlcNAc modification and diabetes.

PMID- 15944816
TI  - Characteristics of histopathological and ultrastructural features of placental
      villi in pregnant Nepalese women.
AB  - The placenta is an important functional unit for gas transfer between mother and
      fetus. The placental membrane, consisting of trophoblast layer interposed between
      maternal and fetal blood, plays an active role for intensity of respiration, but
      no morphological evidence has been documented. Until now, it has been reported
      that fetal growth retardation and increased fetal mortality rate usually could be
      seen at high altitude. In an attempt to find the cause of high perinatal
      mortality rate in Nepal, this study was undertaken to examine pathologically
      about 1000 Himalayan placentas obtained in Nepal and Tibet since 1977, and the
      results were compared with those of 5500 Japanese placentas at Saitama Medical
      School since 1990. In this study, characteristics of ultrastructural features of
      the Nepalese placental villi investigated in recent years are reported. (1) The
      gross characteristics of placental pathology in the Himalayan group were
      represented by marked subchorionic fibrin deposits and increased chorionic cysts
      in contrast to low incidence of intervillous thrombosis compared with those of
      the Japanese group. (2) As characteristics of histological findings of the
      placental villi between Himalayan and Japanese groups, the incidence of
      chorangiosis and chorangioma in the Himalayan group was significantly higher than
      that in the Japanese group. (3) Accompanying an increase of vasculosyncytial
      membrane (VSM) in the villi, thickness and separation of basement membrane of the
      syncytium in addition to increased apoptosis of syncytial cell nuclei were
      recognized. (4) As characteristic ultrastructural features of chorionic villi of
      Nepalese placentas, an increase of mitochondria and cystic formation of rough
      endoplasmic reticulum (rER), in addition to appearance of lamellar bodies similar
      to alveolar epithelial type II cell in organellae of the syncytium, were
      observed. These ultrastructural changes of the placental villous capillaries may
      be ascribed to hypervascularization caused by the chronic hypoxic state. It is,
      therefore, presumed that trophoblast cells may play an important role for gas
      transfer mechanism under such a hypoxic state at high altitude.

PMID- 15944817
TI  - Secretion of human chorionic gonadotropin in early pregnancy.
AB  - Remarkable secretion from the syncytial trophoblast of chorionic villi was
      observed in early pregnancy. Histology and histochemistry revealed many
      cytoplasmic protrusions containing numerous secretory granules, which were of
      basophilic glycoprotein in nature. Also, immunohistochemistry proved that these
      were human chorionic gonadotropin (hCG). Electron microscopy clarified the
      overall secretory process, which started with the production of small granules in
      the Golgi complex; then, the granules migrated toward the cell surface,
      increasing their size by fusing with each other, and gathered in cytoplasmic
      protrusions, then liquefied to be liberated by a mode of exocytosis into the
      maternal bloodstream (intervillous space). This remarkable hCG secretion,
      morphologically represented by the many cytoplasmic protrusions containing
      numerous secretory granules, arose synchronously on the surface of almost all
      chorionic villi. This phenomenon was limited to the eighth and ninth weeks of
      gestation, concurring with the maximal hCG concentration of maternal blood serum
      during pregnancy.

PMID- 15944818
TI  - Localization of thymidine phosphorylase in breast cancer tissue.
AB  - Thymidine phosphorylase levels are higher in some human cancer tissues than in
      adjacent normal tissue. However, the ultrastructural localization of thymidine
      phosphorylase in cancer tissue has been demonstrated only in advanced gastric and
      colorectal cancer. We investigated the localization of thymidine phosphorylase in
      breast cancer tissue by immunohistochemistry and its ultrastructural localization
      by immunoelectron microscopy. Surgically resected specimens from 30 cases of
      breast cancer were analyzed. Immunohistochemical analysis revealed that cancer
      cells were positive in 13 cases. However, there were 21 cases that showed
      thymidine phosphorylase-positive inflammatory cells in cancer tissue. Thymidine
      phosphorylase-positive staining was detected among both cancer cells and
      inflammatory cells in 11 cases. Thymidine phosphorylase was diffusely positive in
      the cytoplasm of cancer cells and specifically positive in mitochondria of
      neutrophils and specific cytoplasmic granules of macrophages in cancer tissue by
      immunoelectron microscopy. These findings suggest that thymidine phosphorylase is
      produced by macrophages and is present in mitochondria of neutrophils and
      cytoplasmic granules of cancer cells.

PMID- 15944819
TI  - Ultrastructural findings of cutaneous nerves in patients with Hunter's syndrome
      following hematopoietic stem cell transplant.
AB  - Hematopoietic stem cell transplant (HSCT) has been performed on patients with
      Hunter's syndrome. If applied, evaluation of recovery in various organs is needed
      for long-term follow-up. However, it remains unclear whether HSCT is effective
      against the neurological involvement in Hunter's syndrome, and morphological
      evaluation of recovery is inconsistent. We observed the degree of cutaneous nerve
      involvement in patients with Hunter's syndrome ultrastructurally before and after
      HSCT. Electron microscopic studies revealed that membrane-bound clear vacuoles
      were still observed in the cytoplasm of endoneurial fibroblasts and Schwann cells
      2 months and 2 years, respectively, after HSCT. On the other hand, only a few
      vacuoles were present in dermal fibroblasts at 2 months after HSCT, and these
      disappeared within 2 years. These results suggest that the persistence of clear
      vacuoles in endoneurial fibroblasts and Schwann cells indicates a disturbed
      internal condition in the endoneurium 2 years after HSCT. Skin biopsies can be
      used in patients with Hunter's syndrome to study peripheral nerves for long-term
      follow-up to evaluate morphological efficacy.

PMID- 15944820
TI  - A morphological study of the pacemaker cells of the aganglionic intestine in
      Hirschsprung's disease utilizing ls/ls model mice.
AB  - Hirschsprung's disease is a congenital aganglionic neural disorder of the
      segmental distal intestine characterized by unsettled pathogenesis. The
      relationship between Hirschsprung's disease and pacemaker cells (PMC), which
      almost corresponds to that of the interstitial cells of Cajal (ICC), was
      morphologically observed at the level of the intermuscular layer corresponding to
      Auerbach's plexus using ls/ls mice. These mice are an ideal model because of
      their large intestinal aganglionosis and gene abnormalities, which are similar to
      the human form of the disease. Immunostaining using anti-c-kit receptor antibody
      (ACK2), a marker of PMC, applied to whole-mount muscle-layer specimens, revealed
      the presence of c-kit immunopositive multipolar cells with many cytoplasmic
      processes in normal mice. For ls/ls mice, however, there were significantly fewer
      processes. The average number of processes per positive cell of 2.5 for the
      aganglionic large intestine was fewer than 3.5 for the large and small intestine
      of normal mice, indicating the inability to form connections between nerves and
      PMC in the aganglionic intestine. For normal mice with an Auerbach's plexus, the
      process attachment of ICC to the Auerbach's plexus was observed by scanning
      electron microscopy. However, for ls/ls mice no attachment to the intermuscular
      nerve without Auerbach's plexus was found, although transmission electron
      microscopy showed no difference in the cell structure and organelles of the c-kit
      immunopositive cells between the normal and ls/ls mice. These findings suggest
      that in the aganglionic intestine of Hirschsprung's disease, aplasia of enteric
      ganglia induces secondary disturbances during the normal development of
      intestinal PMC.

PMID- 15944821
TI  - Basal cell carcinoma arising from a keratinous cyst of the skin: a case report
      and review of the literature.
AB  - Although keratinous cysts of the skin are frequently seen, malignant
      transformation is a rare event. Here we report a case of basal cell carcinoma
      arising in the wall of the keratinous cyst, and we review 12 other such Japanese
      cases.

PMID- 15944822
TI  - Accommodative lag under habitual seeing conditions: comparison between myopic and
      emmetropic children.
AB  - PURPOSE: To determine whether or not myopic children have a larger lag of
      accommodation than emmetropic children under natural seeing conditions. METHODS:
      In 61 myopic children (age, 9.5 +/- 1.3 years; spherical equivalent refractive
      error, -6.50 to -1.00 D), accommodative response was objectively measured while
      they were binocularly viewing a target at 50.5, 32.5, 20.9, or 16.0 cm (1.98-6.25
      D) through fully correcting glasses. In the 33 children who habitually wore
      spectacles, the accommodative responses were also measured while they wore their
      own spectacles. As controls, 18 emmetropic children were recruited. Accommodative
      response gradients and lags were compared between the groups after calibration
      for residual refractive errors and the vertex distance of the glasses. RESULTS:
      With fully correcting glasses, the myopic children showed a larger mean lag of
      accommodation than the emmetropic children, as well as wide intersubject
      variation. However, when the children wore their habitual, usually
      undercorrecting, spectacles, accommodative lags markedly decreased, and a
      significant correlation was found between residual refractive errors after
      correcting for the spectacles and accommodative lags. Myopic children with near
      point exophoria tended to show smaller lags of accommodation. CONCLUSION: Under
      binocular viewing conditions, myopic children when viewing the target through
      fully correcting glasses tend to show larger lags of accommodation than
      emmetropic children, but the lags of accommodation are usually reduced by their
      spectacle undercorrection.

PMID- 15944823
TI  - Eyelid fusion and epithelial differentiation at the ocular surface during mouse
      embryonic development.
AB  - PURPOSE: To investigate epithelial differentiation at the ocular surface of the
      developing mouse eye by examining temporal and spatial changes in the expression
      of specific keratins. METHODS: Ocular tissues, including the entire eyeball,
      conjunctiva, and eyelid, of mouse embryos at embryonic day (E) 12.5 to E18.5 as
      well as of adult mice were examined by hematoxylin-eosin staining and by
      immunohistochemistry with antibodies to keratins K4, K10, K12, and K14. RESULTS:
      Hematoxylin-eosin staining revealed that eyelid fusion occurred at E17.5. Keratin
      immunohistochemistry demonstrated that: (1) K4 was expressed before K12, which in
      turn was expressed before K10; (2) expression of K4, K12, and K14 was spatially
      heterogeneous in the epithelia of the eyelid invaginations before eyelid fusion,
      but thereafter was continuous and homogeneous in the entire conjunctival
      epithelium, corneal epithelium, and basal cell layer of the surface epithelia,
      respectively; and (3) K10 immunoreactivity was not detected before eyelid fusion
      but was apparent in the epidermis of the eyelid thereafter. CONCLUSIONS: Eyelid
      fusion is a critical period for differentiation of the ocular surface ectoderm
      into the epithelia of the conjunctiva, cornea, and eyelid skin. The conjunctival
      epithelium differentiates before the corneal epithelium, which in turn
      differentiates before the eyelid epidermis.

PMID- 15944824
TI  - Comparison of topical dexamethasone and topical FK506 treatment for the
      experimental allergic conjunctivitis model in BALB/c mice.
AB  - PURPOSE: To evaluate the efficacy of topical dexamethasone and topical FK506
      treatment on allergic inflammation in conjunctiva, we performed a comparative
      study using a mouse experimental allergic conjunctivitis model. METHODS: The
      experimental allergic conjunctivitis model was developed by ovalbumin (OVA)
      instillation after OVA sensitization by intraperitoneal application of a mixed
      solution of OVA and aluminum hydroxide. The Balb/c mice of the experimental
      allergic conjunctivitis model were divided into three groups, depending on
      whether or not they received topical treatment and which type of treatment they
      received. The allergy group comprised six mice without topical treatment; the
      dexamethasone (Dx) group comprised six mice receiving topical 0.1% dexamethasone
      ointment treatment; and the FK506 (FK) group comprised six mice receiving topical
      0.1% FK506 ointment treatment. The negative control group comprised six mice with
      neither sensitization nor topical treatment. For the histological examination,
      frozen sections of the eyelids, eyeballs, and lacrimal glands were stained with
      acid Giemsa stain or, in the immunohistochemical method, with alkaline
      phosphatase-antialkaline phosphatase (APAAP), for CD4. Densities of eosinophils
      and CD4-positive lymphocytes in the conjunctival tissue were counted. Productive
      C epsilon gene expression in the conjunctival tissue, including the lacrimal
      gland, was also evaluated by reverse transcriptase polymerase chain reaction (RT
      PCR). RESULTS: In the histological study, the cell density of eosinophils
      infiltrating into subconjunctival tissues was 66.3 +/- 34.7 cells/mm(2) (mean +/-
      SD) for the allergy group, 2.5 +/- 4.2 cells/mm(2) for the Dx group, 4.2 +/- 8.6
      cells/mm(2) for the FK group, and 3.7 +/- 7.6 cells/mm(2) for the negative
      control group. The cell density of CD4-positive cells infiltrating into
      subconjuctival tissues was 145.9 +/- 66.4 cells/mm(2) for the allergy group, 10.0
      +/- 12.9 cells/mm(2) for the Dx group, 10.1 +/- 15.5 cells/mm(2) for the FK
      group, and 21.7 +/- 17.8 cells/mm(2) for the negative control group. The allergy
      group showed significant differences in the density of eosinophils and CD4
      positive cells compared with those of the Dx (P < 0.0001) and FK (P < 0.0001)
      groups. In the RT-PCR study, the expression of productive C epsilon gene was
      positive in the Dx group, but negative in the allergy group, the FK group, and
      the negative control group. CONCLUSIONS: Topical Dx and FK506 treatments were
      both efficacious in suppressing eosinophil and lymphocyte infiltration into
      subconjunctival tissue in the mouse experimental allergic conjunctivitis model.
      However, the influence of their IgE productive mechanisms seemed to differ,
      causing different efficacy of productive C epsilon gene expression in the
      conjunctival tissue.

PMID- 15944825
TI  - Anticardiolipin IgG antibody and homocysteine as possible risk factors for
      retinal vascular occlusive disease in thai patients.
AB  - PURPOSE: To assess the role of serum anticardiolipin IgG antibody and fasting
      plasma homocysteine levels as risk factors for retinal vascular occlusive disease
      in Thai patients. METHODS: This is a retrospective, case-control study. Forty-one
      consecutive patients with recent onset of retinal vascular occlusive diseases
      were enrolled. In conjunction with a routine laboratory work up, serum
      anticardiolipin IgG antibody and plasma homocysteine were evaluated. Ninety
      volunteers without a history of retinal vascular occlusive disease were chosen as
      controls. RESULTS: In general, mean levels of anticardiolipin IgG antibody and
      homocysteine did not differ between the patients and controls. However, when the
      groups without a history of underlying systemic diseases were compared, there
      were statistically significant differences in the anticardiolipin IgG antibody
      level between patients and controls (mean 12.24 +/- 8.66 and 7.70 +/- 6.69 GPL
      units/ml, respectively) with a P value of 0.024. CONCLUSIONS: No association was
      found between plasma homocysteine level and retinal vascular occlusion in our
      patient population. A high level of anticardiolipin IgG antibody is shown to be a
      risk factor only in patients without a history of underlying systemic diseases.
      The effect of anticardiolipin IgG antibody on the development of retinal vascular
      occlusive disease appears to be limited and may not be a major cause.

PMID- 15944826
TI  - Interexaminer differences in the traction test of the superior oblique tendon.
AB  - PURPOSE: The traction test of the superior oblique tendon is used for the manual
      evaluation of the looseness or tightness of the tendon. Because of the subjective
      nature of this test, knowledge of other clinical findings may lead to a bias in
      its interpretation. We studied interexaminer differences in the results of the
      test to assess the reliability of this traction test. METHODS: Examiner A
      examined all of the patients and collected all clinical findings, including the
      results of magnetic resonance imaging. Each of the nine noninformed examiners
      participated in one or more traction tests without prior information regarding
      the clinical findings of the patient. The traction tests were performed on 31
      patients under general anesthesia. The examiners performed the traction test
      alternately with examiner A and evaluated the laxity and tightness in the tendon
      based on a nine-step scale (-4 to +4). The results were recorded in a masked
      manner, and later a comparison between the evaluation results of examiner A and
      those of the other examiners was made. RESULTS: Examiner A and the other
      examiners were in agreement within one grading step on 27 of the 31 (87.1%)
      traction tests. CONCLUSIONS: We demonstrated that the interexaminer differences
      in the interpretations of the traction test were acceptable, and that after the
      noninformed examiners had performed the test several times, their interpretations
      became closer to those of examiner A.

PMID- 15944827
TI  - Transition from upbeat to downbeat nystagmus observed in a patient with
      Wernicke's encephalopathy.
AB  - BACKGROUND: We report an unusual case of Wernicke's encephalopathy presenting
      with transient upbeat nystagmus that changed to a persistent downbeat nystagmus.
      CASE: A 27-year-old man presented with upbeat nystagmus. Three months earlier, he
      had been diagnosed with Wernicke's encephalopathy after fasting for a month.
      OBSERVATIONS: This diagnosis was supported by his symptoms (ataxia, a confused
      state). Clinical recovery followed thiamine therapy. His upbeat nystagmus had
      linear slow phases with average amplitude and frequency (+/-SD) during fixation
      straight ahead of 2.8 +/- 0.7 degrees and 4.6 +/- 2.2 Hz, respectively. Two
      months later, the primary position upbeat nystagmus had diminished and downbeat
      nystagmus (0.9 +/- 0.5 degrees and 3.2 +/- 0.7 Hz on average) for a 20 degrees
      downward gaze had developed. Then, 8 months later, he showed only downbeat
      nystagmus, which obeyed Alexander's law. His primary position downbeat nystagmus
      was completely suppressed by clonazepam, a gamma-aminobutyric acid (GABA)
      agonist. CONCLUSIONS: Owing to an underlying central vestibular imbalance, even
      after the recovery of acute neurological symptoms, Wernicke's encephalopathy can
      be complicated by persistent downbeat nystagmus, which can be treated by a GABA
      agonist.

PMID- 15944828
TI  - Efficacy and complications after trabeculectomy with mitomycin C in normal
      tension glaucoma.
AB  - PURPOSE: To evaluate the efficacy of and complications after trabeculectomy using
      mitomycin C (MMC) in Japanese normal-tension glaucoma (NTG) patients by a
      retrospective analysis based on the Kaplan-Meier life table method. METHODS:
      Clinical records of 39 NTG patients who underwent trabeculectomy with 0.04% MMC
      and had postoperative follow-up periods of 3 years or more (50.5 +/- 8.4 months,
      mean +/- SD) were reviewed. Postoperative intraocular pressure (IOP) at every 1
      or 2 months, complications, visual acuity, and visual field at every 6 months
      were recorded. RESULTS: IOP significantly decreased from 15.9 +/- 1.9
      preoperatively to 8-11 mmHg throughout the postoperative follow-up period (P <
      0.0001). The life table analysis, in which failure of IOP control was defined as
      an IOP above a level either 30% or 20% lower than the preoperative IOP at three
      consecutive visits, showed a cumulative survival rate of 39.4 +/- 7.8% (mean +/-
      SEM) or 41.3 +/- 8.9%, respectively, at 4 years after surgery. Mean deviation of
      the visual field results did not significantly change (P > 0.5). The cumulative
      survival rate from postoperative late-onset hypotony was 74.7 +/- 6.3% at 4 years
      after surgery. Postoperative complications observed were shallow anterior chamber
      (six eyes), choroidal detachment (nine eyes), hypotonous maculopathy (seven
      eyes), bleb leak (one eye), cataract development (three eyes), and blebitis (two
      eyes). No eyes developed endophthalmitis. CONCLUSIONS: In NTG patients,
      trabeculectomy with MMC showed significant efficacy in reducing IOP up to 4 years
      after surgery. Since risks of postoperative complications are unavoidable,
      indications for surgery should be carefully considered, and careful follow-up is
      necessary to avoid severe postoperative complications.

PMID- 15944829
TI  - Frosted branch angiitis secondary to macular choroidal neovascularization in a
      chinese woman.
AB  - BACKGROUND: This is perhaps the first report of frosted branch angiitis secondary
      to choroidal neovascularization (CNV) from China. We describe a case of frosted
      branch angiitis associated with macular CNV. CASE: A 19-year-old Chinese woman
      complained of metamorphopsia and blurred vision in the right eye on August 27,
      2002. OBSERVATIONS: Fluorescein angiography demonstrated CNV in the macula. Five
      months later, focal and atrophic choroidal scars were observed in the macular
      area. She complained of blurred vision again on April 14, 2003. Iridocyclitis and
      frosted branch angiitis were found in both fundi. Following treatment with
      systemic acycloguanosine and corticosteroids for 4 months, the fundi recovered
      almost completely. CONCLUSIONS: A case of frosted branch angiitis secondary to
      macular choroidal neovascularization is reported in a Chinese woman. The relation
      between frosted branch angiitis and CNV remains to be further explored.

PMID- 15944830
TI  - Clinical course of macular edema in two cases of interferon-associated
      retinopathy observed by optical coherence tomography.
AB  - BACKGROUND: Interferon (IFN)-associated retinopathy is typically characterized by
      retinal hemorrhages and cotton wool spots at the posterior fundus, but visual
      function is usually maintained. With the use of optical coherence tomography
      (OCT), two patients with IFN-associated retinopathy who had developed macular
      edema and reduced visual acuity during the clinical course of IFN therapy were
      observed. CASES: A 37-year-old man with chronic hepatitis C and a 59-year-old man
      with chronic myeloid leukemia, both of whom had received IFN therapy, were
      referred to our outpatient clinic. The former patient had complained once that
      his visual acuity had decreased after the termination of IFN therapy, and the
      latter patient complained twice during IFN therapy that his visual acuity had
      decreased. OBSERVATIONS: In both patients, at the time of the visual
      disturbances, macular edema was clearly observed by OCT. Hypoalbuminemia and
      thrombocytopenia were observed at this time also. After the remission of the
      hypoalbuminemia and thrombocytopenia, the macular edema observed by OCT
      disappeared and visual acuity returned to normal. CONCLUSION: During and after
      IFN therapy, OCT is a useful examination technique for revealing macular edema in
      patients who have decreased vision. Ophthalmologists should be aware of the
      ocular side effects of IFN therapy and carefully monitor patients for the
      possible occurrence of hypoalbuminemia and thrombocytopenia. Jpn J Ophthalmol
      2005;49:231-234 (c) Japanese Ophthalmological Society 2005.

PMID- 15944831
TI  - Bilateral, nearly simultaneous anterior ischemic optic neuropathy complicated by
      diabetes and bilateral, small, crowded optic discs.
AB  - BACKGROUND: Bilateral simultaneous anterior ischemic optic neuropathy (AION) is
      uncommon. We report a case of bilateral and nearly simultaneously occurring AION.
      CASE: A 61-year-old man was referred to our hospital with bilateral optic disc
      edema. OBSERVATIONS: Visual field testing demonstrated inferior nasal defect OD
      and inferior defect OS. Fluorescein angiography showed a delay of dye filling in
      the superior part of the optic disc in both eyes. The patient had poorly
      controlled diabetes. A mild increase in erythrocyte sedimentation rates and
      creactive protein was observed, but the results of temporal artery biopsy were
      negative. His optic discs were small and lacked biological cups, which has been
      identified as a risk factor for developing AION. CONCLUSIONS: The complications
      of the structural anomaly, also known as "disc at risk," and diabetes might have
      caused the bilateral and nearly simultaneously occurring AION.

PMID- 15944832
TI  - Clinical manifestations and management of orbital mucoceles: the role of
      ophthalmologists.
AB  - PURPOSE: To report the clinical features of orbital mucoceles and discuss the
      role of ophthalmologists in the management of patients with orbital mucoceles.
      METHODS: A retrospective chart review was performed of all patients with orbital
      mucoceles treated at the National Taiwan University Hospital from 1990 through
      2002. The basic profiles, clinical features, and the management of the patients
      with orbital mucoceles were recorded and analyzed. RESULTS: The records of a
      total of 15 patients (aged 22 to 76, mean 45.5 years) with orbital mucoceles were
      selected for this study. The initial presentations included proptosis in ten
      patients (66.7%), diplopia in five (33.3%), ocular movement limitation in four
      (26.7%), periorbital pain in four (26.7%), palpable mass lesion in four (26.7%),
      ptosis in three (20.0%), decreased visual acuity in three (20.0%), headache in
      two (13.3%), and pupil abnormality with relative afferent papillary defect in one
      (6.67%). Of the 15 patients, the origins of the orbital mucocele were in the
      frontoethmoidal sinus in six (40.0%), the ethmoidal sinus in three (20.0%), the
      frontal sinus in three (20.0%), the maxillary sinus in one (6.7%), and the
      sphenoidal sinus in two (13.3%). The transcaruncular approach for the management
      of orbital mucoceles was performed in eight cases, the Lynch approach in three
      cases, the transforniceal approach in two cases, and functional endoscopic sinus
      surgery in one case. After surgery, no recurrence was noted. CONCLUSIONS: The
      frontoethmoidal sinus was the commonest origin of an orbital mucocele, and
      proptosis was the most frequent sign in patients with an orbital mucocele. All
      cases showed a favorable response to surgical intervention, and the
      transcaruncular approach may offer a good surgical option for the management of
      orbital mucoceles, especially for ophthalmologists.

PMID- 15944833
TI  - Incarceration of the inferior oblique muscle branch of the oculomotor nerve in
      two cases of orbital floor trapdoor fracture.
AB  - BACKGROUND: Incarceration of the inferior oblique muscle (IO) branch of the
      oculomotor nerve may occur in cases of orbital floor trapdoor fracture. CASES:
      Two orbital floor trapdoor fracture cases, with lesions located just outside of
      the inferior rectus muscle but without its incarceration, were examined pre- and
      postoperatively for visual acuity, intraocular details, the nine diagnostic
      ocular positions of gaze, binocular single vision field with the Hess chart, and
      by computed tomography (CT). One case was also examined by magnetic resonance
      imaging (MRI; T1-weighted images). A forced duction test was conducted
      intraoperatively. OBSERVATIONS: Each case presented good visual acuity and
      neither globe showed any injury. Motility disturbance of the IO was shown in each
      case by binocular single vision field testing and the Hess chart. The possibility
      of the incarceration of the IO branch of the oculomotor nerve, which runs from
      the incarcerated lesion to the superior belly of the IO, in an orbital floor
      trapdoor fracture was shown on CT and MRI. Intraoperative forced duction testing
      revealed a restriction due to the incarceration of the connective tissue septa.
      CONCLUSIONS: As inferred from the CT and MRI analyses conducted in this study, IO
      palsy may be one of the causes of ocular motility disturbance of the IO in an
      orbital floor trapdoor fracture, in addition to the ocular motility disturbance
      due to the connective tissue septa.

PMID- 15944834
TI  - A case of vogt-koyanagi-harada disease associated with malignant lymphoma.
AB  - BACKGROUND: Vogt-Koyanagi-Harada disease (VKH), an inflammatory ocular disorder
      characterized by bilateral granulomatous panuveitis and a variety of extraocular
      manifestations, has been reported to be associated with various immune disorders
      but has not been linked to malignant lymphoma (ML). CASE: We present here a case
      of VKH associated with a recurrence of ML. OBSERVATIONS: A 69-year-old man who
      initially had ML presented with a history of sudden bilateral visual acuity loss.
      Funduscopy showed papilloedema and serous retinal detachment in both eyes, and a
      diagnosis of VKH was reached soon thereafter. Chest X-ray and an abdominal
      computed tomography scan indicated the metastatic focus of the ML. A recurrence
      was suspected because the ML-associated soluble interleukin-2 receptor (sIL-2R)
      in the serum was highly elevated. Treatment successfully resolved both the ML and
      the VKH. The inflammatory activities of VKH and ML were found to correlate with
      the serum levels of sIL-2R. CONCLUSIONS: This case suggests an association
      between sIL-2R levels and disease activity in VKH and ML, and provides additional
      evidence that VKH can be induced by immune disorders caused by high sIL-2R levels
      in ML.

PMID- 15944835
TI  - Twenty-gauge Transconjunctival Vitrectomy.
AB  - PURPOSE: To describe a new 20-gauge transconjunctival vitrectomy procedure that
      we designed, to evaluate its usefulness, and to compare two different methods of
      use. METHODS: The records of 431 patients (433 eyes) who underwent 20-gauge
      transconjunctival vitrectomy at the Surugadai Hospital of Nihon University
      between March 2003 and January 2004 were studied retrospectively. In surgical
      method 1, 20-gauge wounds were made through the conjunctiva and sclera together.
      In surgical method 2, 20-gauge conjunctival openings were made 2 mm posterior to
      the sclerotomies. Absorbable sutures were used to stitch the scleral and
      conjunctival openings simultaneously in both methods. RESULTS: A 20-gauge
      transconjunctival vitrectomy has various benefits and is indicated for nearly all
      ocular diseases. Moreover, it is not limited by the intraocular instruments
      required. However, since cannulas were not placed in all ports, conjunctival
      edema occurred more easily with surgical method 2 owing to the leakage of
      perfusion fluid. CONCLUSIONS: This new 20-gauge transconjunctival vitrectomy
      procedure has various benefits and is indicated for nearly all ocular diseases.
      It is not limited by the intraocular instruments required.

PMID- 15944837
TI  - Unusual posterior hyaloid strand in a young child with optic disc pit
      maculopathy: intraoperative and histopathological findings.
AB  - BACKGROUND: The mechanism responsible for optic disc pit maculopathy is unclear,
      but abnormal vitreous structures, including the anomalous Cloquet's canal at the
      optic disc pit, have been suggested as important factors. CASE: We report the
      intraoperative and ultrastructural findings of an unusual posterior vitreous
      strand in the eye of an 8-year-old girl with optic disc pit maculopathy.
      OBSERVATIONS: The patient presented with decreased vision in the left eye.
      Examination of the left eye revealed a best-corrected visual acuity (VA) of 0.08
      and a macular detachment associated with an optic disc pit. Vitrectomy was
      performed with the adjunctive use of triamcinolone acetonide intraoperatively.
      The presence of an unusual posterior hyaloid strand tightly attached to the
      margin of the optic disc pit was noted. An unusual movement of this strand was
      observed during the surgery. The strand was excised, and fluid-gas exchange was
      performed using gas tamponade with 20% SF(6). After 12 months, a complete macular
      reattachment was obtained, with the VA improving to 1.2. Electron microscopic
      examination of the removed strand revealed abundant thick collagen fibrils with a
      frame of fine fibrils. CONCLUSION: The unusual posterior vitreous strand
      connected to the optic disc pit may have contributed to the pathogenesis of
      maculopathy in this young child.

PMID- 15944836
TI  - Radiation retinopathy caused by low dose irradiation and antithyroid drug-induced
      systemic vasculitis.
AB  - BACKGROUND: We report on a patient with Graves' disease with radiation
      retinopathy caused by low-dose irradiation and antithyroid drug-induced
      antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. CASE: A 38-year
      old woman with Graves' disease presented with bilateral blurred vision,
      microaneurysms, telangiectasia, and macular edema. The patient was examined by
      ophthalmoscopy and fluorescein angiography, and radiation retinopathy was
      diagnosed. OBSERVATIONS: The patient had been treated with low-dose irradiation
      for her Graves' ophthalmopathy a few years earlier. She also had ANCA-positive
      vasculitis induced by the antithyroid drug (propylthiouracil, PTU) that had been
      prescribed for her at that time. Because of multiple avascular areas on both
      retinas, she was treated by intensive retinal photocoagulation to control
      progressive retinopathy. CONCLUSIONS: The radiation doses used to treat Graves'
      disease ophthalmopathy are low. Nevertheless, there is still a risk of radiation
      retinopathy developing in patients with PTU-induced ANCA-positive vasculitis.

PMID- 15944838
TI  - The effects of intracameral ropivacaine on the corneal endothelium.

PMID- 15944839
TI  - DNA analysis for diagnosis of x-linked juvenile retinoschisis when clinical
      examination is difficult in a young child.

PMID- 15944840
TI  - Oxidative stress in kidney and liver of alloxan-induced diabetic rabbits: effect
      of repaglinide.
AB  - The aim of this study was to analyse the effect of the new oral antidiabetic drug
      repaglinide on antioxidant factors and lipid peroxidation in tissues of alloxan
      induced diabetic rabbits after 4 and 8 weeks treatment. The activity of
      superoxide dismutase (diabetic vs. control values, mean+/-S.E.M., p<0.05) in
      diabetic kidney was diminished (1.5+/-0.2 vs. 2.8+/-0.3 and 1.8+/-0.1 vs. 2.9+/
      0.3 U/mg protein) and significantly increased after 8 weeks of repaglinide
      treatment (2.4+/-0.2 U/mg protein). Catalase activity was significantly increased
      in diabetic liver (67.5+/-3.6 vs. 39.7+/-5.6 and 62.3+/-2.7 vs. 52.6+/-5.3
      micromol H(2)O(2)/min/mg protein) and normalised by repaglinide (49.2+/-4.0 and
      41.2+/-3.8 micromol H(2)O(2)/min/mg protein). In diabetic kidney the level of
      ascorbic acid was diminished after 4 weeks (1.5+/-0.1 vs. 3.0+/-0.1 micromol/g
      tissue) and increased after the drug treatment (2.0+/-0.2 micromol/g tissue). In
      diabetic kidney the level of lipid peroxidation products was elevated (33.3+/-2.4
      vs. 23.7+/-2.4 and 29.5+/-3.1 vs. 18.2+/-0.8 nmol/g tissue) and diminished by
      repaglinide (10.3+/-1.4 and 13.3+/-3.0 nmol/g tissue). This study shows that
      oxidative stress in diabetic tissues is partly corrected by repaglinide. The drug
      does not affect glucose concentration and its antioxidative effect is not
      secondary to its action on hyperglycaemia. This study suggests an additional
      advantage of repaglinide which contributes to its effectiveness in therapy.

PMID- 15944841
TI  - Influence of diabetes on peripheral bone mineral density in men: a controlled
      study.
AB  - The aims of the study were to (1) compare peripheral bone mineral density (BMD)
      in men with diabetes to peripheral BMD in non-diabetic men, and (2) explore
      factors which may predict BMD in diabetic men. Ninety men with type 2 diabetes
      and 35 men with type 1 diabetes were randomly selected for participation via a
      computerised database. Fifty healthy males were also recruited. All patients had
      peripheral BMD measured by dual energy Xray absorptiometry (DEXA) at the non
      dominant distal radius. Information on a number of clinical parameters was
      obtained by direct questioning, and from patient case notes. The mean age (95%
      confidence interval (CI)) of the type 1 diabetic group, type 2 diabetic group and
      control group were, respectively: 49.3 years (44.6-53.9), 62.8 years (60.7-64.8)
      and 38.5 (34.9-42.1) years. Median (95% CI) Z-scores for the three groups were: 
      0.18 (-0.68 to +0.32), +0.19 (-0.14 to +0.49) and -0.02 (-0.4 to +0.31),
      respectively (p=not significant). Only body mass index (BMI) was correlated with
      BMD in the type 1 diabetic group, and only BMI and age were correlated with BMD
      in type 2 diabetics. There was no correlation between BMD and glycosylated
      haemoglobin concentration (HbA(1)c), disease duration or presence of
      microvascular or macrovascular complications in either of the diabetic groups. We
      did not find any significant difference in peripheral BMD between patients with
      type 1 diabetes, type 2 diabetes and controls.

PMID- 15944842
TI  - Regression of microalbuminuria in type 1 diabetic patients: results of a
      sequential intervention with improved metabolic control and ACE inhibitors.
AB  - The objective was to evaluate the effect of improved metabolic control and ACE
      inhibition used sequentially in the treatment of type 1 diabetic patients with
      microalbuminuria. We studied 44 consecutive type 1 diabetic patients with
      microalbuminuria not previously treated with ACE inhibitors. Improved metabolic
      control (optimisation period) was attempted for 6-12 months and patients with
      persistent microalbuminuria were subsequently treated with ACE inhibitors.
      Stepwise logistic regression analysis included the variables age, age at diabetes
      onset, duration of diabetes, HbA1c, initial albumin excretion rate (AER) and mean
      blood pressure as predictors of final AER. Thirty per cent of patients regressed
      to normoalbuminuria after the optimisation period, and 58% of them maintained
      normal AER 4.5+/-1.3 years later (3-7 years). Patients achieving normoalbuminuria
      had lower baseline AER (53+/-22 vs. 94+/-63 mg/24 h, p=0.012). The initial AER
      level was the only factor associated with final AER (r=0.58, p=0.021). Thirty
      patients with persistent microalbuminuria were treated with ACE inhibitors for
      two years, 35.5% of whom regressed to normal AER. Patients achieving
      normoalbuminuria after ACE inhibitor treatment had lower baseline AER (55+/-24
      vs. 132+/-75 mg/24 h, p=0.03). The initial AER was the sole predictor of final
      AER (r=0.51, p<0.013). Overall, the sequential use of improved metabolic control
      and ACE inhibitor therapy resulted in long-term normalisation of AER in 47.4% of
      patients. The sequential implementation of improved metabolic control and ACE
      inhibitor therapy had a long-term beneficial effect in type 1 diabetic patients
      with microalbuminuria. We propose that type 1 diabetic patients with
      microalbuminuria could benefit from a period of metabolic improvement before the
      initiation of ACE inhibitor therapy.

PMID- 15944843
TI  - Anaesthesia-induced hyperglycaemia early in life is not predictive for
      development of diabetes in diabetes-prone BB rats.
AB  - Type 1 diabetes (T1D) is an autoimmune disease in genetically predisposed
      individuals characterised by selective destruction of the beta-cells. Development
      of diabetes is in the asymptomatic pre-diabetic period characterised by impaired
      first-phase insulin response and the first clinical symptom is elevated blood
      glucose (BG). It is still uncertain whether stress or incidental hyperglycaemia
      can be regarded as predictors for development of T1D or not, even when
      immunologic and genetic markers for T1D are considered. The aim of this study was
      to investigate if there was any relationship between elevated BG in 30-day-old
      anaesthetised pre-diabetic diabetes-prone Bio Breeding (BB-DP) rats and later
      development of diabetes. Rats anaesthetised by intraperitoneal (ip) injection for
      islet transplantation displayed significantly higher BG values (Delta1.27 mmol/l,
      p=8.27x10(-12)) compared to non-anaesthetised non-transplanted rats, indicating
      that ip injection and/or anaesthesia induce a higher BG level. Linear regression
      analysis of BG and time of onset of diabetes in transplanted and non-transplanted
      BB-DP rats revealed no correlation (R(2) at 0.0075 and 0.0324 and p-values at
      0.56 and 0.23 respectively). We were not able to identify any association or
      correlation between the induced temporary hyperglycaemia in 30-day-old BB-DP rats
      and later development of diabetes.

PMID- 15944844
TI  - Prevalence of aspirin resistance in patients with type 2 diabetes.
AB  - Aspirin resistance has been recognised to occur in patients with cardiovascular
      disease and is associated with poor clinical prognosis. The purpose of the
      present study was to evaluate the prevalence of aspirin resistance in 172
      patients with diabetes mellitus type 2 (DM-2). Platelet function of 172
      consecutive patients with type 2 diabetes on chronic aspirin therapy was
      evaluated. The effect of aspirin was assessed using the platelet function
      analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the
      time required to close a small aperture in a biologically active membrane.
      Resistance to aspirin was defined as a normal collagen/epinephrine-induced
      closure time (82-165 s). Aspirin responders were defined when closure time was >
      or =300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be
      resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106
      (61.6%) were responders. Univariate analysis revealed that aspirin non-responders
      were significantly younger (p<0.05) compared to aspirin responders. A significant
      number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin
      resistance can be evaluated by point-of-care testing and should be recognised in
      diabetic patients that are treated for primary or secondary prevention.

PMID- 15944845
TI  - Increased serum resistin levels in patients with type 2 diabetes are not linked
      with markers of insulin resistance and adiposity.
AB  - The role of resistin in human biology remains uncertain. We measured serum
      resistin levels in Japanese patients with (n=111) and without (n=98) type 2
      diabetes mellitus and investigated the significance of this hormone in the
      pathophysiology of diabetes. The levels of serum adiponectin and leptin were also
      measured. Resistin levels were increased significantly in patients with type 2
      diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml,
      p=0.0013). However, there was no correlation in either patient group between
      serum resistin levels and markers of insulin resistance, obesity or
      hyperlipidaemia. These results were in direct contrast to the data of leptin or
      adiponectin, both of which were closely related to these clinical markers of
      diabetes. Multivariate regression analysis on the combined data of the two groups
      demonstrated that the presence of diabetes and HDL cholesterol levels were
      significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035;
      HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive
      protein and resistin adjusted for BMI. Taken together, these findings demonstrate
      that serum resistin levels are increased in patients with type 2 diabetes, but
      this increase is not linked to markers of insulin resistance or adiposity.
      Further studies are necessary to elucidate the significance of serum resistin
      concentration in human pathophysiology.

PMID- 15944846
TI  - Glycogen accumulation in renal tubules, a key morphological change in the
      diabetic rat kidney.
AB  - Patients with diabetic nephropathy, characterised pathologically by
      glomerulosclerosis, may account for up to 40% of end-stage renal cases. The short
      term (within 3 months) streptozotocin- or alloxan-induced rat model is often used
      but glomerulosclerosis is seldom reported and it is unclear what the primary
      renal lesions are. Diabetic rats were studied at 1, 3 and 6 months after a single
      injection of alloxan. Both methacrylate and paraffin-embedded renal sections were
      obtained and stained with PAS and haematoxylin. A morphometric study was
      performed with stereological methods to obtain the volumes and lengths or
      diameters of renal tubules and glomeruli. A key morphological change associated
      with sustained hyperglycaemia was the accumulation of glycogen granules in about
      half of the distal tubules and thin segments starting from 1 month after the
      experiment, which was then extended to about half of the proximal tubules at 6
      months. Renal hypertrophy was seen with a 9% increase in the tubule diameter but
      not in the total length; glomerular morphology was basically unaffected. Further
      studies are needed to establish whether glomerulosclerosis would occur in longer
      term and whether this animal model would be appropriate to study the human
      condition of diabetes mellitus in terms of renal damage.

PMID- 15944848
TI  - [From research to practice].

PMID- 15944847
TI  - Moxifloxacin monotherapy compared to amoxicillin-clavulanate plus roxithromycin
      for nonsevere community-acquired pneumonia in adults with risk factors.
AB  - The objective of this study was to assess the efficacy and safety of moxifloxacin
      versus amoxicillin-clavulanate plus roxithromycin (comparator) in adult community
      acquired pneumonia (CAP) patients with risk factors. In this comparative,
      randomized, multicenter, open-label study, patients hospitalized for CAP received
      a 10-day oral treatment with either moxifloxacin (400 mg o.d.) or amoxicillin
      clavulanate (1,000/125 mg t.i.d.) plus roxithromycin (150 mg b.i.d.). Clinical
      and bacteriological outcomes were assessed during test of cure and follow-up
      visits (5-7 days and 21-28 days after the end of treatment, respectively). Of 349
      randomized patients, 346 were included in the intent-to-treat analysis and 289 in
      the per-protocol analysis. Their baseline characteristics were comparable. The
      most frequent risk factors for mortality were age >65 years (50.0%), alcoholism
      (23.1%), and comorbidities (50.6%); chronic obstructive pulmonary disease (COPD)
      (25.4%) and diabetes mellitus (13.6%) were the most common associated
      comorbidities. A causative pathogen was documented in 66 of 346 (19.1%) of the
      patients (including 21 with positive blood cultures). Respective per-protocol
      clinical success rates at test-of-cure (primary efficacy endpoint) for
      moxifloxacin and comparator were 131 of 151 (86.8%) and 120 of 138 (87.0%), with
      a 95% confidence interval (CI) of -8.0-7.6 for the difference. Bacteriological
      success rates (eradication) were 23 of 30 (76.7%) and 23 of 31 (74.2%); rates for
      patients with positive blood cultures were 10 of 14 and 4 of 6. Persistent
      clinical success rates at follow-up were 118 of 120 (98.3%) and 102 of 106
      (96.2%), with a 95%CI of -2.2-6.4 for the difference. The intent-to-treat
      analysis confirmed these results. Adverse events associated with moxifloxacin and
      the comparator drug were reported for 42 of 171 (24.6%) and 50 of 175 (28.6%) of
      the patients, respectively, and comprised predominantly digestive disorders,
      which occurred in 9.4% and 21.1%. On the basis of these results, once-daily oral
      moxifloxacin alone is as effective as amoxicillin-clavulanate plus roxithromycin
      for the treatment of CAP in patients with risk factors.

PMID- 15944849
TI  - [New study findings in cardiology].

PMID- 15944850
TI  - Reliability of a criterion-based test of athletes with knee injuries; where the
      physiotherapist and the patient independently and simultaneously assess the
      patient's performance.
AB  - A new criterion-based evaluation test method, has been developed in order to
      assess the functional ability of athletes with knee injuries, 'Tests for Athletes
      with Knee-injuries' (TAK). The physiotherapist and the patient assess
      independently and simultaneously the patient's performance. The TAK comprises
      eight demanding functional activities with emphasis on strength, stability,
      springiness and endurance. OBJECTIVES: To evaluate the inter-rater and intra
      rater reliability of TAK between the physiotherapist's and the patient's
      assessments. Further, to evaluate the relation between the functional tests in
      TAK and the isokinetic quadriceps muscle strength. MATERIALS AND METHODS: Fifty
      nine subjects were included in the study. Thirty-one were anterior cruciate
      ligament (ACL) reconstructed, fourteen were ACL-injured not reconstructed and
      fourteen were healthy athletes. The inter-rater-reliability was evaluated by
      assessments of 59 subjects carried out by two independent physiotherapists using
      visual observation. The assessment was rated on a 0-10-point scale according to
      five elaborate criteria drawn up for each test. Simultaneously, the subjects were
      asked to rate their own performance on each test using a 0-10-point scale. The
      intra-rater-reliability of TAK was evaluated by a test-retest of 31 patients. The
      relation between the physiotherapist's and the patients' ratings as well as of
      the patients' ratings at two different occasions were evaluated. Isokinetic
      quadriceps muscle strength was measured in a Biodex dynamometer on all 59
      subjects in order to study the relation between quadriceps muscle strength and
      the results of the functional tests in TAK. RESULTS: Inter-rater-reliability
      showed good consistency between the assessments of the two physiotherapists in
      seven of eight tests (kappa = 0.62-0.78). The intra-rater-reliability was
      moderate to good (kappa = 0.43-0.65) in the test-retest study. The consistency of
      the physiotherapist and the patients' assessments differed, but showed good
      correlation. The consistency of the test-retest study of the patients' assessment
      was low. The correlation between the isokinetic quadriceps muscle strength
      measured in a Biodex dynamometer and the results of the functional tests was
      moderate in this study. CONCLUSIONS: This criterion-based test method for
      athletes with knee injuries showed good inter-rater reliability and acceptable
      intra-rater reliability for the physiotherapists' assessment. The consistency of
      the patients' ratings was low. The correlation between isokinetic quadriceps
      muscle strength and functional tests in TAK was moderate. The validity has not
      been evaluated in this study but will be done in the future.

PMID- 15944852
TI  - Evaluation of a novel case-based training program (d3web.Train) in hematology.
AB  - The new media such as the internet and digital imaging offer new opportunities in
      medical education. In addition to conventional lectures, we developed a case
      based simulation training program of 17 hematology cases using the novel training
      system d3web.Train. We evaluated the assessment of this internet course by
      medical students, as well as their results in the hematology exam. From a group
      of 150 students, 47 worked through at least one case and solved 435 cases in
      total; in average, these students solved 9.5 cases. Eighteen different students
      filled in a questionnaire about the training system and 68 questionnaires about
      individual cases. The main results were the students found the cases very helpful
      (1.5+/-0.6 on a scale from 1=very helpful to 5=not at all), the training system
      very good (1.4+/-0.5 on a scale from 1 to 6), and want to work with it further
      (1.2+/-0.4 on a scale from 1 to 5). During the final examination, those 16
      students who answered that they had solved more than 5 from the 17 cases scored
      significantly better (two-sided t test, p<0.01) in the hematological part of the
      exam than those 34 students solving 0 to 5 cases. To our knowledge, this is the
      first student evaluation of a case-based training program in general hematology.
      The d3web.Train system offers a new and great tool for creating a training
      program in a reasonable amount of time, because it is able to process available
      patient records.

PMID- 15944851
TI  - [Gastric banding: surgical and technical aspects].
AB  - Morbid obesity (body mass index >40 kg/m(2)) is a risk factor for cardiovascular,
      pulmonary, metabolic, neoplastic, and psychologic sequelae. Laparoscopic
      adjustable gastric banding (LAGB) has been established for more than 10 years as
      a good, safe therapy for morbid obesity if strict operational indications are
      observed and there is multidisciplinary, long-term follow-up. The technical
      aspects of LAGB are important for its long-term success. The pars flaccida
      technique is standard and leads to fewer complications. The bands should be
      placed above the bursa omentalis. Different types of bands are available. Band
      fixation by suturing with nonabsorbable stitches prevents slippage. The port
      system also must be fixated by nonabsorbable sutures.

PMID- 15944853
TI  - [Patients in forensic and general psychiatry. Do risk assessment measures detect
      differing risks of future violence?].
AB  - BACKGROUND: The aim of this study was to assess the potential for future violent
      behaviour comparing patients recruited from forensic and general psychiatric
      wards in Germany. PATIENTS AND METHODS: Fifty patients were recruited from a
      forensic hospital and 29 from a general psychiatric hospital. In the weeks
      preceding discharge, structured assessments of the future risk of violent
      behaviour were completed using the HCR-20. RESULTS: There was little difference
      in the risk presented by the two groups. Forensic patients presented an elevated
      risk of violence because of historical factors, while the risk among patients
      from general psychiatry was due to clinical symptoms. CONCLUSION: Some criminal
      offences could be prevented if more time and effort were spent in general
      psychiatric practice in identifying patients at high risk for violence and in
      reducing symptoms of psychoses before discharge.

PMID- 15944854
TI  - Xylanase production by fungal strains on spent sulphite liquor.
AB  - Xylanase production by seven fungal strains was investigated using concentrated
      spent sulphite liquor (SSLc), xylan and D: -xylose as carbon substrates. An SSLc
      based medium induced xylanase production at varying levels in all of these
      strains, with Aspergillus oryzae NRRL 3485 and Aspergillus phoenicis ATCC 13157
      yielding activities of 164 and 146 U ml(-1), respectively; these values were
      higher than those obtained on xylan or D: -xylose with the same fungal strains.
      The highest xylanase activity of 322 U ml(-1) was obtained with Aspergillus
      foetidus ATCC 14916 on xylan. Electrophoretic and zymogram analysis indicated
      three xylanases from A. oryzae with molecular weights of approximately 32, 22 and
      19 kDa, whereas A. phoenicis produced two xylanases with molecular weights of
      about 25 and 21 kDa. Crude xylanase preparations from these A. oryzae and A.
      phoenicis strains exhibited optimal activities at pH 6.5 and 5.0 and at 65 and 55
      degrees C, respectively. The A. oryzae xylanolytic activity was stable at 50
      degrees C over the pH range 4.5-10. The crude xylanase preparations from these A.
      oryzae and A. phoenicis strains had negligible cellulase activity, and their
      application in the biobleaching of hardwood pulp reduced chlorine dioxide
      consumption by 20-30% without sacrificing brightness.

PMID- 15944855
TI  - Visual shape recognition with contour propagation.
AB  - A neural architecture is presented that encodes the visual space inside and
      outside of a shape. The contours of a shape are propagated across an excitable
      neuronal map and fed through a set of orientation columns, thus creating a
      pattern which can be viewed as a vector field. This vector field is then burned
      as synaptic, directional connections into a propagation map, which will serve as
      a "shape map". The shape map identifies its own, preferred input when it is
      translated, deformed, scaled and fragmented, and discriminates other shapes very
      distinctively. Encoding visual space is much more efficient for shape recognition
      than determining contour geometry only.

PMID- 15944857
TI  - Society news June 2005.

PMID- 15944856
TI  - Robust sound classification through the representation of similarity using
      response fields derived from stimuli during early experience.
AB  - Models of auditory processing, particularly of speech, face many difficulties.
      Included in these are variability among speakers, variability in speech rate, and
      robustness to moderate distortions such as time compression. We constructed a
      system based on ensembles of feature detectors derived from fragments of an onset
      sensitive sound representation. This method is based on the idea of 'spectro
      temporal response fields' and uses convolution to measure the degree of
      similarity through time between the feature detectors and the stimulus. The
      output from the ensemble was used to derive segmentation cues and patterns of
      response, which were used to train an artificial neural network (ANN) classifier.
      This allowed us to estimate a lower bound for the mutual information between the
      class of the input and the class of the output. Our results suggest that there is
      significant information in the output of our system, and that this is robust with
      respect to the exact choice of feature set, time compression in the stimulus, and
      speaker variation. In addition, the robustness to time compression in the
      stimulus has features in common with human psychophysics. Similar experiments
      using feature detectors derived from fragments of non-speech sounds performed
      less well. This result is interesting in the light of results showing aberrant
      cortical development in animals exposed to impoverished auditory environments
      during the developmental phase.

PMID- 15944859
TI  - Measuring unconscious knowledge: distinguishing structural knowledge and judgment
      knowledge.
AB  - This paper investigates the dissociation between conscious and unconscious
      knowledge in an implicit learning paradigm. Two experiments employing the
      artificial grammar learning task explored the acquisition of unconscious and
      conscious knowledge of structure (structural knowledge). Structural knowledge was
      contrasted to knowledge of whether an item has that structure (judgment
      knowledge). For both structural and judgment knowledge, conscious awareness was
      assessed using subjective measures. It was found that unconscious structural
      knowledge could lead to both conscious and unconscious judgment knowledge. When
      structural knowledge was unconscious, there was no tendency for judgment
      knowledge to become more conscious over time. Furthermore, conscious rather than
      unconscious structural knowledge produced more consistent errors in judgments,
      was facilitated by instructions to search for rules, and after such instructions
      was harmed by a secondary task. The dissociations validate the use of these
      subjective measures of conscious awareness.

PMID- 15944860
TI  - Processing abstract sequence structure: learning without knowing, or knowing
      without learning?
AB  - Constant interaction with a dynamic environment-from riding a bicycle to
      segmenting speech-makes sensitivity to the sequential structure of the world a
      fundamental dimension of information processing. Accounts of sequence learning
      vary widely, with some authors arguing that parsing and segmentation processes
      are central, and others proposing that sequence learning involves mere
      memorization. In this paper, we argue that sequence knowledge is essentially
      statistical in nature, and that sequence learning involves simple associative
      prediction mechanisms. We focus on a choice reaction situation introduced by Lee
      (1997), in which participants were exposed to material that follows a single
      abstract rule, namely that stimuli are selected randomly, but never appear more
      than once in a legal sequence. Perhaps surprisingly, people can learn this rule
      very well. Or can they? We offer a conceptual replication of the original
      finding, but a very different interpretation of the results, as well as
      simulation work that makes it clear how highly abstract dimensions of the
      stimulus material can in fact be learned based on elementary associative
      mechanisms. We conclude that, when relevant, memory is optimized to facilitate
      responding to events that have not occurred recently, and that sequence learning
      in general always involves sensitivity to repetition distance.

PMID- 15944861
TI  - The generation of conscious awareness in an incidental learning situation.
AB  - The purpose of the present experiments was to investigate the generation of
      conscious awareness (i.e., of verbal report) in an incidental learning situation.
      While the single-system account assumes that all markers of learning, verbal or
      nonverbal, index the same underlying knowledge representation, multiple-systems
      accounts grant verbal report a special status as a marker of learning because
      they assume that the nonverbal and verbal effects of learning rely on different
      memory representations. We tested these two accounts in two experiments in which
      we held the amount of learning in the nonverbal memory system constant while
      manipulating independent variables aimed at affecting learning in the declarative
      system. The results of both experiments revealed significant differences in
      verbal report between experimental conditions, but no significant differences in
      response times. Overall, these results provide clear evidence in favor of the
      multiple-systems account.

PMID- 15944862
TI  - Treatment of refractory chronic inflammatory demyelinating polyneuropathy with
      interferon beta 1B.

PMID- 15944863
TI  - Narcolepsy increased L-PGDS (beta-trace) levels correlate with excessive daytime
      sleepiness but not with cataplexy.
AB  - OBJECTIVES: Alterations in the prostaglandin-D-system have been found in animal
      sleep experiments and disorders that present with hypersomnia or sleep
      disturbances. The recently demonstrated involvement of the leptomeningeal
      lipocalin-type prostaglandin-Dsynthase (L-PGDS) (beta-trace) in human
      physiological sleep encouraged us to investigate its role in the pathophysiology
      of narcolepsy. METHODS: In a pilot study, serum LPGDS and melatonin
      concentrations were assessed in 14 narcoleptic patients during undisturbed sleep
      and total sleep deprivation, compared with those from 14 healthy controls during
      undisturbed sleep. Excessive daytime sleepiness was measured by a standardized
      questionnaire (Epworth sleepiness scale, ESS). RESULTS: In narcoleptic patients,
      markedly increased baseline L-PGDS levels were significantly correlated with the
      ESS score, but not with the degree of cataplexy. Serum L-PGDS concentrations in
      patients as well as in controls followed a time-dependent fluctuation with
      evening increases, highest values during the night and in the morning. Compared
      with controls, patients exhibited significant/increased amplitude of circulating
      L-PGDS without any suppression by total sleep deprivation. CONCLUSION: These
      findings indicate that the prostaglandin-D-system contributes to the
      pathophysiology of narcolepsy, e. g. the regulation of excessive daytime
      sleepiness. Since it has been suggested that L-PGDS is also involved in
      neurodegenerative disorders, there may be a more specific role of the
      prostaglandin- D-system in narcoleptic aetiogenesis. Moreover, its linkage with
      the immune system as well as with human sleep regulation offers a direct access
      for investigating both systems.

PMID- 15944866
TI  - Is "cardiovascular protection" by estrogens due to inhibition of the sympathetic
      nervous system?

PMID- 15944867
TI  - Sibutramine and the sympathetic nervous system in obese humans.

PMID- 15944868
TI  - Effect of acute transdermal estrogen administration on basal, mental stress and
      cold pressor-induced sympathetic responses in postmenopausal women.
AB  - Administration of estrogen has vascular effects through poorly defined mechanisms
      that may include sympathetic withdrawal. To define the effects of acute estrogen
      administration on sympathetic responses, nineteen healthy postmenopausal women
      (age 54+/-2 years) were studied after application of a placebo or estrogen patch
      for 36 hours, in random order. A p-value, adjusted for multiple comparisons, of
      <0.017 was used to determine statistical significance. Heart rate, blood
      pressure, and norepinephrine spillover were measured at rest, during mental
      stress (Stroop test), and during a cold pressor test. Estrogen did not attenuate
      basal or stimulated hemodynamic responses significantly. The increase in mean
      arterial pressure after the Stroop test (5.9+/-1.2mm/ Hg on placebo vs 6.1+/
      1.6mm/Hg on estrogen, p=0.9) and after the cold pressor test (12.6+/-2.4mm/Hg on
      placebo vs 13.0+/-2.2 mm/Hg on estrogen, p=0.8) did not differ. Basal, mental
      stress and cold pressor-stimulated norepinephrine spillover were not
      significantly affected by short-term estrogen administration. Norepinephrine
      spillover tended to be higher after estrogen (1296.2+/-238 ng/min) than placebo
      (832.5+/-129 ng/min) (p=0.02) at baseline and after the Stroop test (1881.1+/-330
      ng/min vs 1014.6+/-249 ng/min) (p=0.02). Acute transdermal estrogen
      administration did not attenuate norepinephrine spillover or sympathetically
      mediated hemodynamic responses.

PMID- 15944869
TI  - Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese
      hypertensive patients--sibutramine and blood pressure.
AB  - BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is a
      common adjunctive obesity treatment. Acute studies in healthy subjects suggested
      that an inhibitory central nervous mechanism might attenuate the peripheral
      stimulatory effect on the sympathetic nervous system. This notion has not been
      tested in overweight and obese patients. METHODS: We conducted a randomized,
      controlled clinical study in hypertensive patients with BMI > or = 27 to < 40
      kg/m(2). After 4 week placebo run-in period patients were randomized to four
      different antihypertensive treatments or placebo. After 4 weeks of
      antihypertensive therapy, patients were additionally treated with sibutramine 15
      mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing
      and a graded head-up tilt test at the end of each phase. RESULTS: Mean body
      weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run
      in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2,
      145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after
      antihypertensive titration (ns) and end of sibutramine treatment (ns),
      respectively. Blood pressure was affected similarly during head up tilt testing.
      The systolic blood pressure response to cold pressor testing was diminished with
      sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure
      oscillations in the supine position (p<0.01). CONCLUSIONS: Resting blood pressure
      tends to increase with sibutramine, whereas blood pressure during sympathetic
      stimulation and low frequency blood pressure oscillations are decreased. These
      paradoxical changes are consistent with previous studies in healthy subjects and
      suggest a combination of peripheral and central nervous system mechanisms.

PMID- 15944870
TI  - Prolonged latency in the baroreflex mediated vascular resistance response in
      subjects with postural related syncope.
AB  - In addition to the gain, the delay of the baroreflex response plays an important
      role in the maintenance of cardiovascular system stability. Additionally when
      postural changes induce sudden drops in blood pressure, a delayed response may
      fail to maintain sufficient cerebral perfusion pressure. We tested the hypothesis
      that the delay of the carotid baroreceptor reflex is impaired in subjects with
      poor orthostatic tolerance. An orthostatic test with 60 degrees head-up tilt, and
      progressive lower-body negative pressure was performed on 27 patients with
      histories of unexplained syncope and 13 control subjects. The test was stopped at
      the onset of presyncope and time to presyncope was taken as a measure of
      orthostatic tolerance. Twelve patients had normal tolerance and thirteen patients
      had low tolerance. We measured beat-to-beat blood pressure (Finapres) and
      brachial artery blood flow velocity (Doppler ultrasonography). Before the test,
      we determined the response of forearm vascular resistance (mean arterial
      pressure/mean brachial artery velocity) to loading/unloading of carotid
      baroreceptors by the application of neck suction/pressure (-/+30 mmHg) to a
      chamber fitted overlying the carotid sinus. We measured the gain in the response
      (maximum percentage change from baseline value in vascular resistance divided by
      the neck collar pressure) and the latency in the response (delay of the maximum
      change in vascular resistance after neck-collar stimulation). Results are
      reported as means +/- SEM. In the three groups, there were no differences in the
      sensitivity of the vascular resistance response after baroreceptor
      loading/unloading. Following baroreceptor unloading, the latency of the response
      was 14.0+/-1.3 seconds in early fainters, 9.3+/-0.7 seconds in normal patients
      and 10.1+/-1.2 seconds in controls. The latency in blood pressure rise was 11.1+/
      1.3 seconds in early fainters, 7.9+/-0.9 seconds in normal patients and 7.2+/-1.0
      seconds in controls. The results following baroreceptor loading were more
      scattered. The early fainters still had a tendency to show prolonged latency.
      These results suggest that the delay in the baroreflex response plays an
      important role in postural related syncope.

PMID- 15944871
TI  - Abnormal heart rate and blood pressure responses to baroreflex stimulation in
      multiple sclerosis patients.
AB  - Cardiovascular autonomic neuropathy has been previously reported in patients with
      multiple sclerosis (MS) using standard reflex tests. However, no study has
      separately evaluated both parasympathetic and sympathetic cardiovascular
      autonomic regulation. We therefore assessed the baroreflex-mediated vagal and
      sympathetic control of the heart rate and sympathetic control of the blood
      vessels in MS patients using sinusoidal neck stimulation. We studied 13 multiple
      sclerosis patients aged 28-58 years and 18 healthy controls aged 26-58 years. The
      carotid baroreflex was stimulated by sinusoidal neck suction (0 to -30 mmHg) at
      0.1 Hz to assess the autonomic control of the heart and blood vessels, and at 0.2
      Hz to assess the vagal control of the heart. Continuous recordings were made of
      blood pressure, electrocardiographic RR-interval and respiration, with breathing
      paced at 0.25 Hz. Spectral analysis was used to evaluate the magnitude of the low
      frequency (LF, 0.03-0.14 Hz) and high frequency (HF, 0.15-0.50 Hz) oscillations
      in RR-interval and blood pressure in response to the sinusoidal baroreceptor
      stimulation. Responses to the applied stimulus were assessed as the change in the
      spectral power of the RR-interval and blood pressure fluctuations at the
      stimulating frequency from the baseline values. The increase in the power of 0.1
      Hz RR-interval oscillations during the 0.1 Hz neck suction was significantly
      smaller (p<0.01) in the MS patients (4.47+/-0.27 to 5.62+/-0.25 ln ms(2)) than in
      the controls (4.12+/-0.37 to 6.82+/-0.33 ln ms(2)). The increase in the power of
      0.1 Hz systolic BP oscillations during 0.1 Hz neck suction was also significantly
      smaller (p<0.01) in the MS patients (0.99+/-0.19 to 1.96+/-0.39 mmHg(2)) than in
      the healthy controls (1.27+/-0.34 to 9.01+/-4.10 mmHg(2)). Neck suction at 0.2 Hz
      induced RR-interval oscillations at 0.2 Hz that were significantly smaller
      (p<0.05) in the patients (3.22+/-0.45 ln ms(2)) than in the controls (5.27+/-0.29
      ln ms(2)). These results indicate that in MS patients, baroreflex dysfunction is
      not only restricted to the cardiovagal limb of the baroreflex, but that the
      sympathetic modulation of the blood vessels is also affected.

PMID- 15944872
TI  - The value of autonomic testing in postural tachycardia syndrome.
AB  - Postural tachycardia syndrome (POTS) is a fairly common condition that may or may
      not be associated with autonomic neuropathy. In a retrospective analysis, we
      compared two groups of patients based on clinical and autonomic criteria, those
      with POTS in isolation (POTS-Alone), and POTS with evidence of autonomic
      neuropathy (POTS-AN). Of 260 records reviewed, 57 patients met the criteria for
      POTS; 38 (67%) patients assigned to the POTS-Alone group and 19 (33%) patients
      assigned to the POTS-AN group. A decreased sweat output on the quantitative
      sudomotor axon reflex test is the most frequent abnormal finding in the POST-AN
      group suggesting sympathetic cholinergic neuropathy. Clinically, headache and
      gastrointestinal symptoms were more frequent among the POTS-AN group. Therefore,
      POTS may exist in isolation and may differ from those associated with AN.

PMID- 15944873
TI  - Circadian periodicity of heart rate variability in hospitalized angor patients.
AB  - The relationship between unstable angor (angina) and circadian periodicity of
      heart rate variability (HRV) was explored in a group of patients hospitalized in
      a coronary care unit (CCU). Patients were classified as normal (whose symptoms
      had non-cardiovascular origin, n=8), moderate angor (n=13) and severe angor
      (n=11). A fourth group of ambulatory healthy volunteers (n=12) was included.
      Individual 24 h Holter records were analyzed, mean RR and standard deviation of
      RR (SDNN) being obtained from 1 h-length windows. For frequency domain analysis,
      5 min-length windows were employed. The spectral components analyzed were total
      power (spectral power between 0.01 and 0.5 Hz), low frequency power (LF: power
      between 0.04 and 0.15 Hz), and high frequency power (HF: power between 0.15 and
      0.4 Hz). In addition, LF to HF areas ratio (L/H) was computed. Mesor, amplitude
      and acrophase for every 24 h rhythm were calculated by cosinor analysis. As
      compared to ambulatory controls, admission to the CCU diminished amplitude and
      phase-delayed the circadian oscillation of most HRV parameters, except for SDNN.
      Moderate angor patients showed decreased amplitude of RR and L/H and augmented
      amplitude of SDNN when compared to normal hospitalized subjects. A phase delay of
      about 1.5 h for RR intervals and a phase advance of 3.5-6 h for LFA and SDNN were
      found in the moderate angor group when compared to normal. Amplitude of 24 h
      variation of total power decreased in severely angor patients and the circadian
      oscillation of HF (an indicator of vagal control on the heart) became free
      running. A phase delay of 2.5 h in SDNN acrophase was found in severely affected
      patients when compared to moderate. The results indicate that severity of
      unstable angor correlates with desynchronization of parasympathetic control of
      heart rate.

PMID- 15944874
TI  - Sympathetic skin response in premenstrual syndrome.
AB  - Premenstrual syndrome is a term which includes a broad group of emotional,
      behavioral and physical symptoms that occur for several days before menses and
      subside following the menstrual period. Many women experience premenstrual
      syndrome symptoms, particularly physical ones such as breast tenderness and
      swelling. Approximately 5-10% women suffer from severe premenstrual syndrome and
      another 30-40% have moderate symptoms. Premenstrual syndrome continues to be an
      unsolved problem. In this study, we evaluated 24 premenstrual syndrome patients
      and 20 healthy women in the control group. The ages of the women were 22-34 years
      (mean +/- SD: 25+/-3) for the premenstrual syndrome group and 23-34 (25+/-3) for
      the control group. The sympathetic skin response was recorded from the palms,
      soles and genital regions by using electrical stimuli to the median nerve at the
      wrist. The sympathetic skin response was recorded twice, in the follicular and
      late luteal phases of menstruation. The follicular and late luteal phase
      sympathetic skin response of the two groups were compared. The amplitudes and
      latency values of the late luteal and follicular phase sympathetic skin response
      from the premenstrual syndrome group and control group women were statistically
      similar. We also did not find any latency or amplitude difference in the
      sympathetic skin response obtained from the three regions of the premenstrual
      syndrome patients and the control group. We checked sympathetic skin response in
      the symptomatic (late luteal phase) and asymptomatic (follicular phase) periods
      of patients with premenstrual syndrome, a disorder known to have many autonomic
      symptoms, to determine whether there was sudomotor sympathetic involvement. The
      results of our PMS patients indicate at the very least that there is no
      difference with the control subjects as regards peripheral sudomotor functions.

PMID- 15944875
TI  - The human fear-circuitry and fear-induced fainting in healthy individuals--the
      paleolithic-threat hypothesis.
AB  - The Paleolithic-Threat hypothesis reviewed here posits that habitual efferent
      fainting can be traced back to fear-induced allelic polymorphisms that were
      selected into some genomes of anatomically, mitochondrially, and neurally modern
      humans (Homo sapiens sapiens) in the Mid-Paleolithic because of the survival
      advantage they conferred during periods of inescapable threat. We posit that
      during Mid-Paleolithic warfare an encounter with "a stranger holding a sharp
      object" was consistently associated with threat to life. A heritable hardwired or
      firm-wired (prepotentiated) predisposition to abruptly increase vagal tone and
      collapse flaccidly rather than freeze or attempt to flee or fight in response to
      an approaching sharp object, a minor injury, or the sight of blood, may have
      evolved as an alternative stress-induced fear-circuitry response. Such a stable
      (balanced) polymorphism for the hemodynamically "paradoxical" flaccid-immobility
      in response to these stimuli may have increased some non-combatants' chances of
      survival. This is consistent with the unusual age and sex pattern of fear-induced
      fainting. The Paleolithic-Threat hypothesis also predicts a link to various hypo
      androgenic states (e. g. low dehydroxy-epiandrosterone-sulfate. We offer five
      predictions testable via epidemiological, clinical, and ethological/
      primatological methods. The Paleolithic-Threat hypothesis has implications for
      research in the aftermath of man-made disasters, such as terrorism against
      civilians, a traumatic event in which this hypothesis predicts epidemics of fear
      induced fainting.

PMID- 15944876
TI  - Mobile wireless technologies for rehabilitation and independence.

PMID- 15944877
TI  - Consistency and accuracy of measurement of lower-limb amputee anthropometrics.
AB  - Lower-limb amputees often exhibit large fluctuation in residual-limb shape,
      necessitating careful observation and anthropometric measurement for prosthetists
      to ensure socket fit. Anthropometric measurement may become more important as an
      outcome measure indicating success in rehabilitation. This study investigated the
      accuracy and reliability of seven prosthetic anthropometric measurement devices
      as used by a group of eight prosthetic-orthotic practitioners and a group of five
      prosthetic-orthotic students to measure six common anthropometric dimensions on
      three foam positive models of transtibial amputee residual limbs. Two of the
      models were identical, enabling assessment of individual repeatability. Some
      clinically significant errors were noted in the results; however, the general
      variability in measurements was not clinically significant. Students were
      slightly more consistent than practitioners; students were more consistent with
      linear measurements, while practitioners were more consistent with
      circumferential measures. The results further demonstrated that the VAPC
      measurement device used in the study was both inaccurate and unreliable.

PMID- 15944878
TI  - A preliminary investigation into the development of 3-D printing of prosthetic
      sockets.
AB  - The socket is considered an element of major importance in the makeup of a
      prosthesis. Each socket is a tailor-made device, designed to fit the unique
      geometry of the patient's residual limb. The design and manufacture of a
      prosthetic socket traditionally has been a manual process that relies on the use
      of plaster of Paris casts to capture the shape of the patient's residual limb and
      then artisan fabrication techniques to manufacture the socket. Computer-aided
      design and manufacturing technologies have overcome some of the shortcomings of
      the traditional process, but the final manufacture of the prosthetic socket is
      still performed manually. Rapid prototyping (RP), a relatively new class of
      manufacturing technologies, creates physical models directly from three
      dimensional (3-D) computer data. Previous research into the application of RP
      systems to the manufacture of prosthetic sockets has focused on expensive, high
      end technologies that have proven too expensive. This paper investigates the use
      of a cheaper, low-end RP technology known as 3-D printing. Our investigation was
      an initial approach to using a technology that is normally associated with
      producing prototypes quickly, some of which could not be manufactured by
      alternative means. Under normal circumstances, these printed components are weak
      and relatively fragile. However, comfortable prosthetic sockets manufactured with
      3-D printing have been used in preliminary fittings with patients.

PMID- 15944879
TI  - Residual-limb skin temperature in transtibial sockets.
AB  - The insulated environment of the lower-limb prosthesis can result in elevated
      residual-limb skin temperatures that may contribute to skin irritation,
      blistering, and a reduced quality of life. The design and materials of the
      prosthetic socket, suspension system, and liner can potentially alleviate these
      conditions, but the thermal load may vary with activity and location within the
      socket. To characterize the thermal environment at the skin-prosthesis interface,
      we made temperature measurements on five transtibial amputees at 14 locations on
      the residual limbs. After the participants donned their prosthesis and rested in
      the seated position for 15 min, the mean skin temperatures of their residual
      limbs increased by 0.8 degrees Celcius. Subsequent walking for 10 min resulted in
      a 1.7 degrees Celsius total increase in mean skin temperature. Thermal contour
      maps revealed the skin was coolest at the anterior proximal location and warmest
      across the posterior section, correlating with areas of low and high perfusion.
      From the results, we determined that residual-limb skin temperature depends on
      activity and locality. This information may aid in understanding where and why
      skin problems develop on lower-limb residual limbs and may provide design
      requirements for new prosthetic socket systems intended to alleviate temperature
      related discomfort.

PMID- 15944880
TI  - Physical and functional measures related to low back pain in individuals with
      lower-limb amputation: an exploratory pilot study.
AB  - For this study, we compared the physical impairments and functional deficits of
      individuals with lower-limb amputation (LLA) for those with and without low back
      pain (LBP). Nineteen participants with LLA were placed into two groups based on
      visual analog scores of LBP. We assessed functional limitations, iliopsoas
      length, hamstring length, abdominal strength, back extensor strength, and back
      extensor endurance. Data analysis included correlations and t-tests. We found
      significant correlations between pain score and functional limitations, iliopsoas
      length, and back extensor endurance. We also detected significant differences in
      functional limitations, iliopsoas length, back extensor strength, and back
      extensor endurance between those with and without LBP. We saw significant
      differences in back extensor strength and back extensor endurance between those
      with transtibial and transfemoral amputations. Differences exist in physical
      measures of individuals with LLA with and without LBP. Clinicians should consider
      these impairments in individuals with amputation who experience LBP. Because of
      the participants' characteristics, these findings may be applicable to veterans
      with LLA.

PMID- 15944881
TI  - Bending stiffness of the lumbar spine subjected to posteroanterior manipulative
      force.
AB  - This study measured the bending stiffness of the spine when it is subjected to
      posteroanterior mobilization force. The lumbar spine was modeled as an initially
      curved beam column supported over the rib cage and the pelvis. Posteroanterior
      mobilization was assumed to be three-point bending of the beam. The mobilization
      force was measured by the mounting of a force plate onto the manipulation couch,
      where electromagnetic sensors measured the change in spinal curvature. The
      bending stiffness of the spine was derived from the force and curvature data. The
      technique developed in this study provided highly repeatable data. The
      theoretical analysis suggests that the pelvic rotation produced by mobilization
      may be used clinically to indicate the magnitude of the mobilization force.
      Future research may employ the present method to determine how back pain may
      affect the bending stiffness of the spine. The bending stiffness values reported
      in this study will be valuable to future modeling work.

PMID- 15944882
TI  - Temporal symmetries during gait initiation and termination in nondisabled
      ambulators and in people with unilateral transtibial limb loss.
AB  - This study investigated the temporal characteristics of gait initiation and gait
      termination. Ten nondisabled adult volunteers and ten people with unilateral
      transtibial limb loss performed starting and stopping for slow, normal, and fast
      walking speeds. We used kinematic and anthropomorphic data to determine the body
      center of mass (BCOM) position of each subject. The BCOM acceleration was derived
      by double-differentiating the position data. An averaged BCOM acceleration was
      calculated by a filtering of the instantaneous acceleration data at a cutoff
      frequency set by the cadence for elimination of the step-to-step variation. We
      used this averaged acceleration to calculate the time the volunteers needed to
      initiate and terminate gait. The results support the hypothesis that both
      nondisabled ambulators and the subjects with unilateral transtibial limb loss
      initiate and terminate gait in approximately two steps, regardless of the steady
      state walking speed.

PMID- 15944883
TI  - Experimentally induced pain perception is acutely reduced by aerobic exercise in
      people with chronic low back pain.
AB  - This study examined whether subjects with chronic low back pain demonstrate
      exercise-induced analgesia to experimentally induced pressure pain. We employed a
      repeated measures design to study eight subjects with chronic low back pain (mean
      +/- standard deviation age = 40 +/- 10, duration of pain = 7 +/- 4 years). Pain
      ratings were measured immediately before and 2 minutes and 32 minutes after 25
      minutes of cycle ergometry (5 minutes at 50% peak oxygen uptake, then 20 minutes
      at 70% peak oxygen uptake). We based the pain ratings on subject input on a
      visual analog scale at 10-second intervals during the 2-minute pressure pain
      stimulus to the nondominant index finger. Compared with preexercise values, pain
      ratings were significantly (p < 0.05) decreased after exercise at both 2 and 32
      minutes postexercise. We conclude that pressure pain perception can be reduced
      for more than 30 minutes following aerobic exercise from leg cycling among people
      with chronic low back pain.

PMID- 15944884
TI  - Comparison of head- and body-velocity trajectories during locomotion among
      healthy and vestibulopathic subjects.
AB  - The optimal strategies for improving locomotor stability in people with
      vestibulopathy remain unclear. To help identify likely targets for intervention,
      we sought to determine whether vestibulopathic postural control impairment during
      locomotor activity was more localized to either the head or the whole body. We
      used high curvature analysis (HCA) to quantify the smoothness of head- and body
      velocity trajectories during repeated stepping in 18 vestibulopathic and 17
      healthy subjects. We employed a mixed-model repeated measures analysis of
      variance to compare differences in head- and body-trajectory HCA scores. Pearson
      coefficients were used to describe relationships between head- and body
      trajectory HCA scores within each group. The results revealed that neither head-
      nor body-velocity trajectories were relatively more impaired in subjects with
      vestibulopathy. Importantly, however, the smoothness of head and body
      trajectories was more strongly related in subjects with vestibulopathy compared
      with healthy subjects, suggesting that the fundamental motor control impairment
      produced by vestibulopathy may be related to an abnormal coupling of head and
      body motion. We discuss implications for locomotor training in patients with
      vestibulopathy.

PMID- 15944885
TI  - Functional activities characteristics of shoulder complex movements: Exploration
      with a 3-D electromagnetic measurement system.
AB  - The high prevalence of shoulder-related dysfunction has focused increased
      attention on functional activity assessment. This study (1) tested the
      reliability of three-dimensional shoulder complex movements during four
      functional tasks representing different levels of task difficulty, (2)
      characterized the four functional tasks, and (3) examined the relationships
      between age and shoulder movements. Twenty-five asymptomatic subjects, all
      veterans aged 30-82, performed the four functional tasks. Good within-session
      reliability was found (movement pattern: similarity index = 0.81 to 0.97, peak
      values: intraclass correlation coefficients = 0.88 to 0.99). The raising arm to
      overhead height task (hard task) placed the greatest demand on scapular motions
      and humeral elevation (p < 0.005). During the functional tasks, significant
      correlations existed between age and scapular tipping, humeral elevation, and
      scapular upward rotation (r = -0.62 to 0.50, p < 0.05). Correlation results
      indicated that elderly subjects have a greater potential for serratus anterior
      muscle weakness and shoulder capsule tightness.

PMID- 15944886
TI  - Implications of expiratory muscle strength training for rehabilitation of the
      elderly: Tutorial.
AB  - With age, physical functions decline, which influences respiratory performance.
      One of the physical changes associated with aging is sarcopenia, a reduction in
      muscle strength and power. Sarcopenia has been extensively studied in the elderly
      with regard to limb function but less with regard to respiratory function.
      Elderly individuals experience reduced muscle mass and strength in respiratory
      musculature, which may hinder the ability to generate adequate expiratory driving
      force for both ventilatory and nonventilatory activities. Increasing expiratory
      muscle strength may enhance an elderly individual's ability to generate and
      maintain the expiratory driving force critical to cough, speak, and swallow.
      Previous studies demonstrate that expiratory muscle strength training (EMST)
      improves ventilatory and nonventilatory functions. This paper discusses the
      potential impact that EMST can have on the rehabilitation of respiratory muscle
      decline, particularly in the elderly. This tutorial reviews an EMST paradigm, its
      physiological underpinnings, and its potential outcomes.

PMID- 15944887
TI  - Rehabilitation during alcohol detoxication in comorbid neuropsychiatric patients.
AB  - For this study, we evaluated the effectiveness of a cognitive training program in
      improving cognitive function in patients with alcoholism comorbid with another
      neuropsychiatric disorder and going through the subacute phase of detoxication.
      We employed a randomized clinical trial design in which 20 subjects were assigned
      to a five-session cognitive rehabilitation program and 20 subjects were assigned
      to an attention placebo control condition. All subjects received a battery of
      cognitive tests for reasoning, attention, and visual-spatial abilities. These
      tests were repeated at the completion of the study. The training consisted of a
      number of component tasks designed to improve attention, speed of information
      processing, perceptual analysis, and visual-spatial cognition. We plotted
      performance on training results across sessions to detect evidence of learning
      effects. Comparisons of the cognitive tests revealed greater improvement in the
      training as compared to the attention placebo group on measures of attention and
      conceptual flexibility. We concluded that the training produced significant
      improvement over and above natural recovery during detoxication.

PMID- 15944888
TI  - Electromyographic activity imbalances between contralateral back muscles: An
      assessment of measurement properties.
AB  - Electromyographic (EMG) contralateral imbalances of back muscles are often
      interpreted as an aberrant back muscle pattern related to back pain. This study
      assessed different measurement properties (influence of the control of asymmetric
      efforts and of the force level, reliability, and sensitivity to low back status)
      of EMG imbalance parameters. Healthy controls (n = 34) and chronic low back pain
      subjects (n = 55) stood in a dynamometer measuring the principal (extension) and
      coupled (lateral bending, axial rotation) L5/S1 moments during isometric trunk
      extension efforts. The results showed that back pain subjects did not produce
      higher coupled moments than controls. Providing feedback of the axial rotation
      moment to correct asymmetric efforts during the task did not reduce EMG
      contralateral imbalances, except for some extreme cases. Normalized EMG imbalance
      parameters remain relatively constant between 40% and 80% of the maximal
      voluntary contraction. The reliability of EMG imbalance parameters was moderate,
      at best. Finally, neither low back status nor pain location had an effect on EMG
      contralateral imbalances. We conclude that the clinical relevance of EMG
      contralateral imbalances of back muscles remains to be established.

PMID- 15944889
TI  - Bladder-wall and pelvic-plexus stimulation with model microstimulators:
      Preliminary observations.
AB  - Severe urinary retention is not a common condition, but may occur following some
      pelvic surgeries or other medical conditions. Electrical stimulation of the
      bladder has been examined as a means of managing this difficult problem. We
      conducted preliminary investigations in cats to prove the hypothesis that pelvic
      plexus (bladder-neck) stimulation would produce greater micturition response with
      reduced side effects, such as animal movement or discomfort, than bladder-wall
      stimulation with electrodes implanted higher on the bladder wall. We used model
      microstimulators that mimic the look and function of commercial microstimulators,
      but that we constructed. We instrumented four female cats during a survival
      surgery. Animals recovered well and studies were conducted over a 1-month period
      in the conscious animal and under anesthesia. We performed a variety of studies
      with different stimulation parameters and electrode locations to evaluate our
      hypothesis. In the active animal, we supplied only low currents, but two animals
      responded to stimulation with bladder contractions and voiding. Following
      anesthesia, higher stimulating currents resulted in greater bladder contractions
      during stimulation in two of the three animals. In two cases, pelvic-plexus
      (bladder-neck) stimulation induced greater micturition responses than direct
      bladder-wall stimulation. In conclusion, we learned from these preliminary
      observations that stimulation at the pelvic plexus (bladder neck) may induce a
      better micturition response than stimulation higher on the bladder-wall. Newly
      available commercial microstimulators should be further studied for the treatment
      of urinary retention.

PMID- 15944895
TI  - [To our readers: certified continuing education].

PMID- 15944896
TI  - [Supply of tuberculin in Germany].

PMID- 15944897
TI  - [Exercised-induced asthma in soccer players ages from 8 to 13 years].
AB  - The purpose of this study was the detection of exercise induced asthma in soccer
      players aged 8-13 years. Thirty boys, 8-13 years old participated in the study.
      They were coming from an athletic team of north of Thessaloniki. The study
      included clinical examination, administration of a respiratory health
      questionnaire and the exercise -- free running -- test with spirometric
      measurements. Spirometric measurements were performed by using a microspirometer,
      before exercise and 2, 5, 10, 15 and 30 min after a 6 min free running exercise
      (80 - 90 % max heart rate). The highest forced expiratory volume in one second
      (FEV (1)) value before exercise was compared with the lowest of post exercise
      values. The results showed a decline in FEV (1) > 15 % in 12 out of 30 children.
      Particularly, decline in FEV (1) was present in 1 (11 %) out of 9 children with
      free personal medical history but positive family history for asthma, in 3 (25 %)
      out of 12 children with allergies, and in 8 (89 %) out of 9 children with asthma.
      Symptoms were reported by 9 of 12 children with fall in FEV (1) > 15 %, during
      the 6 min exercise test, who had no symptoms during the soccer games.
      Identification of EIA by exercise challenge test in young athletes is a useful
      component for the diagnosis of bronchial hyperresponsiveness. Similar studies
      should be performed on older and younger athletes who participate in different
      sports and games.

PMID- 15944898
TI  - [Pulmonary infection due to Mycobacterium malmoense].
AB  - M. malmoense could be cultivated in sputum samples of a 49-year-old patient with
      destructive pulmonary disease. The conventional antituberculous therapy (started
      because initially a presumptive diagnosis of tuberculosis was established) was
      altered to ethambutol, rifabutin, clarithromycin and ciprofloxacin, followed by a
      long-time therapy with azithromycin or clarithromycin. But till now it was not
      possible to eradicate the mycobacteria from the respiratory tract (insufficient
      compliance, interruptions of the therapy due to side effects, excessive smoking).
      Infections due to M. malmoense are rare events. Many patients have disposing
      underlying diseases. In most cases it is a pulmonary infection. The most frequent
      used antibiotics are rifampicin (or rifabutin), ethambutol and clarithromycin.

PMID- 15944899
TI  - [Prevention of infections of the lower respiratory tract in adults].

PMID- 15944900
TI  - [Tuberculosis in Germany in 2001 and 2002].
AB  - The implementation of the new law on infectious diseases in 2001 and the
      resulting notification of more detailed variables has led to a better knowledge
      about the epidemiology of tuberculosis (TB) in Germany. 7,515 new cases of active
      tuberculosis were notified to the Robert Koch Institute in 2001, and 7,684 cases
      in 2002, corresponding to an incidence of 9.1 (2001) and 9.3 (2002) per 100,000
      inhabitants (as per 1 October, 2003). The slight increase in new cases in 2002 is
      most likely due to under-notification in 2001 because of the new system,
      considering that the previous decline over many consecutive years is continued
      according to the incidence for 2003 (8.7/100,000; n = 7,184). In 2001 as well as
      in 2002 42 % of new TB patients were born outside Germany, and those of foreign
      nationality have a five-fold higher incidence on the average than German
      citizens. The lung remains the most affected organ (80 %). 4,230 (2001) and 4,267
      (2002) were cases of open, i. e., bacteriologically confirmed, pulmonary
      tuberculosis potentially contagious to their immediate contacts. The resistance
      rates are stable in the indigenous population, while patients coming from
      countries with high resistance rates reflect the situation in their countries of
      origin. Over two thirds of TB patients in Germany are hospitalized at some point
      during their disease. The treatment results (78 % on the average in 2001) do not
      reach the WHO target of 85 %. Approximately 7 % of TB patients in Germany still
      die because of this infectious disease.

PMID- 15944901
TI  - [Pulmonary hypertension and sleep-related breathing disorders].
AB  - Pulmonary hypertension (PH), i. e. an increase of mean pulmonary artery pressure
      above 20 mm Hg under resting conditions, can be observed in different forms of
      sleep-disordered breathing (SDB). In obstructive sleep apnea (OSA) the apnea
      associated triggers of hypoxia and intrathoracic pressure swings lead to
      repetitive rises of pulmonary artery pressure during sleep. In 20 - 30 % of these
      patients daytime PH occurs. PH in the setting of OSA is usually mild and rarely
      causes clinically evident cor pulmonale. Effective CPAP therapy has a beneficial
      influence on pulmonary hemodynamics in OSA. Severe congestive heart failure (i.
      e. with a LVEF < 40 %) might provoke pulmonary venous hypertension and thereby
      stimulation of pulmonary stretch and irritant receptors. The ensuing
      hyperventilation leads to a decrease of pCO (2) levels below the apneic threshold
      and thus contributes to the emergence of Cheyne Stokes respiration (CSR) in up to
      one half of the affected patients. Patients suffering from advanced idiopathic
      pulmonary arterial hypertension (IPAH) might show a similar breathing pattern
      while asleep. Possible pathogenetic factors of the nocturnal periodic breathing
      occurring in end-stage IPAH are prolonged circulation times and hypocapnia. In
      conclusion, SDB might cause PH (OSA-associated PH). On the other hand, PH might
      lead to the development of SDB (CSR in congestive heart failure, periodic
      breathing in IPAH).

PMID- 15944902
TI  - Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal
      neurovisceral lipid storage disease. Report of a further patient.
AB  - An infant presented with multifocal myoclonus and cyanotic hypoxemia immediately
      after birth, and severe feeding problems, a protein-losing enteropathy, massive
      ascites and grand-mal epilepsy marked his rapid downhill course, with death at 17
      weeks. At 2 weeks, brain MRI revealed grey matter heterotopias in the parieto
      occipital regions suggestive of a cortical morphogenetic disorder. In cultured
      skin fibroblasts, lipid storage and reduced activities of ceramidase,
      galactosylceramide beta-galactosidase and glucosylceramide beta-glucosidase were
      evident. Autopsy disclosed generalised lysosomal lipid storage with macrophages
      and adrenal cortex prominently affected. The pattern of stored lipids in cultured
      fibroblasts and in dewaxed spleen tissue blocks was compatible with a diagnosis
      of prosaposin (pSap) deficiency (pSap-d). Neuropathologically, there was a
      pronounced generalised neurolysosomal storage combined with a severe depletion of
      cortical neurons and extreme paucity of myelin and oligodendroglia. This
      pathology, in particular the massive neuronal loss, differed from that in other
      neurolipidoses and could be explained by the reduced hydrolysis of multiple
      sphingolipids and the loss of pSap's neurotrophic function. The absence of
      immunostainable saposins on tissue sections and the presence of a homozygous c.1
      A > T mutation in the prosaposin gene confirmed the diagnosis. PSap-d may be an
      underdiagnosed condition in infants with severe neurological and dystrophic signs
      starting immediately after birth.

PMID- 15944903
TI  - Assessment of visual function in children with methylmalonic aciduria and
      homocystinuria.
AB  - The aim of this study was to assess various aspects of visual function in 6
      patients (age range: 9 months to 7 years and 8 months) with methylmalonic
      aciduria and homocystinuria. All patients had an ophthalmological examination and
      were tested with a battery of age-appropriate tests assessing various aspects of
      visual function such as acuity, visual fields and visual attention. None of the
      patients had significant retinal abnormalities but all 6 had nystagmus which was
      associated with strabismus in 3 of the 6. They all had some abnormalities on the
      behavioral tests assessing visual function which appeared to be related to the
      age of the patients. Visual impairment was more severe in the 3 patients below 3
      years of age and milder in the older patients. The presence and the severity of
      abnormalities, in contrast, did not depend on the age at onset or the age when
      treatment was started and were only partly related to brain MRI findings. Severe
      hydrocephalus and basal ganglia involvement were associated with severe visual
      impairment, but abnormal visual findings were also present in the children with
      normal MRI and isolated mild periventricular changes. Our results suggest that
      age, brain lesions and other factors may be responsible for visual abnormalities
      in methylmalonic aciduria and homocystinuria. Further studies using early and
      sequential assessment of visual function are needed to establish whether the
      differences observed between younger and older children may be related to the
      duration of therapy.

PMID- 15944904
TI  - Risk factors for fatality and neurological sequelae after status epilepticus in
      children.
AB  - Using multivariate regression analysis, we examined risk factors for fatality and
      neurological sequelae after status epilepticus (SE) in children. Possible risk
      factors included sex, age at onset, the cause of SE, pyrexia, asthmatic attack
      during SE, past history of seizure, predisposing neurological abnormality,
      seizure duration, type of seizure, and medication with theophylline. Consecutive
      patients with SE, aged 1 month to 18 years, who were referred to Tottori
      University Hospital from 1984 to 2002 were reviewed. Of the 234 patients
      enrolled, 45 patients (19.2 %) showed poor outcomes, namely early death in 9 and
      neurological sequela in 36. Acute neurological insult and progressive
      neurological disease as the cause of SE were very significantly related to poor
      outcome (OR = 33.68, p = 0.000). We excluded 21 patients with the etiology of
      acute neurological insult and progressive neurological disease and then
      reanalyzed risk factors in the remaining 213 patients. Twenty-nine patients (13.6
      %) showed poor outcome, namely early death in 6 and neurological sequela in 23.
      Seizure duration of more than 2 hours (OR = 12.73, p = 0.000) and moderate to
      severe asthmatic attack (OR = 31.61, p = 0.010) were associated with poor
      outcome. These results indicate that long-lasting seizure activity and asthmatic
      attack can exacerbate SE-associated brain injury.

PMID- 15944905
TI  - Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption.
AB  - Cerebral developmental abnormalities occur in various inborn errors of metabolism
      including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and
      others. Associations with abnormalities of the respiratory chain are rare. Here
      we report male and female siblings with microcephaly, a complex neuromigrational
      disorder including ependymal cysts, leptomeningeal and subcortical heterotopia,
      polymicrogyria, multifocal cerebral calcifications, agenesis of the corpus
      callosum, and spongiform changes in brainstem and cerebellum. Intractable lactic
      acidosis, causing death on the first day of life, was associated with severely
      reduced activities of complex I and complex IV. The neuropathological and
      biochemical findings are closely similar to those reported previously. The
      findings confirm a distinct genetic syndrome of disrupted brain development with
      TORCH-like calcifications, and a complex neuronal migration disorder associated
      with a multicomplex disorder of the respiratory chain.

PMID- 15944906
TI  - Pipecolic acid as a diagnostic marker of pyridoxine-dependent epilepsy.
AB  - Pyridoxine-dependent epilepsy, although described some decades ago, may still be
      an underdiagnosed disorder. We have recently described isolated pipecolic acid
      elevations in the plasma and/or CSF of three patients with pyridoxine-dependent
      epilepsy with an intriguing inverse correlation to the oral intake of pyridoxine.
      We have now confirmed these findings in a further 6 unrelated patients with
      pyridoxine-dependent epilepsy. Pipecolic acid in plasma was 4.3- to 15.3 fold
      elevated compared to the upper normal range before pyridoxine and remained in the
      mildly elevated range while on pyridoxine. Pipecolic acid was even more markedly
      elevated in CSF. The extent of pipecolic acid elevation in CSF exceeded that of
      plasma by a factor of 2.2 to 4.8. This clearly discriminates pyridoxine-dependent
      epilepsy from other possible defects with elevated pipecolic acid. Determination
      of pipecolic acid in plasma and/or CSF should be included in the diagnostic work
      up of patients with therapy-resistant seizures. It will in addition prevent
      patients with pyridoxine-dependent epilepsy from experiencing potentially
      dangerous pyridoxine-withdrawal, which until now has been necessary to prove the
      diagnosis.

PMID- 15944907
TI  - Autosomal recessive axonal form of Charcot-Marie-Tooth Disease caused by compound
      heterozygous 3'-splice site and Ser130Cys mutation in the GDAP1 gene.
AB  - A recessive demyelinating subtype of Charcot-Marie-Tooth disease called CMT4 is a
      heterogeneous group of disorders. A relatively frequent form of recessive CMT
      (CMT4 A) has been mapped to the chromosome 8 q21 and shown to be caused by
      mutations in the ganglioside-induced differentiation protein 1 (GDAP1) gene.
      Twenty mutations in the GDAP1 gene have been reported in patients suffering from
      the axonal and demyelinating forms of CMT disease. In this study we report two
      novel mutations in the GDAP1 gene in a patient suffering from CMT2 disease and
      whose parents were asymptomatic carriers of a Ser130Cys and 3'-splice site (311
      1G > A) mutation, respectively.

PMID- 15944908
TI  - SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic
      generalized epilepsy of infancy with generalized tonic-clonic seizures.
AB  - Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized
      epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and
      myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+
      families, all three phenotypes were found associated with mutations in the SCN1A
      gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic
      astatic epilepsy -- including 12 probands of the original cohort used by Doose et
      al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI --
      mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations
      were found in 3 individuals. A frame shift resulting in an early premature stop
      codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI
      (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a
      missense mutation in the conserved pore region (40736 C --> A; R946 S) were
      detected each in a child with SIGEI. We conclude that, independent of precise
      syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A
      mutations in sporadic myoclonic epilepsies of infancy and early childhood.

PMID- 15944909
TI  - Mitochondrial dysfunction in a patient with Joubert syndrome.
AB  - Joubert syndrome is a genetically heterogeneous disorder. The diagnostic criteria
      include episodic hyperventilation, abnormal eye movements, psychomotor
      retardation, hypotonia, ataxia, and the characteristic neuro-imaging findings
      (molar-tooth sign). Many of these clinical features have been observed in new
      borns with mitochondrial disorders as well. Congenital brain malformations,
      including cerebellar hypoplasia, have been described in pyruvate dehydrogenase
      deficiency. Malformations of the vermis and the cerebellar peduncles, with the
      lack of axonal decussations, however, are characteristic for Joubert syndrome but
      unique in patients with mitochondrial disorders. Here, we describe a child with
      Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate
      oxidation rates, decreased ATP production, and a mildly decreased pyruvate
      dehydrogenase complex activity measured in a fresh muscle biopsy. Sequence
      analysis of the PDHc E1 alpha gene and the PDHX genes revealed no mutations. The
      patient received continuous feeding through a feeding tube for two years and
      showed a significant clinical improvement with a complete resolution of the
      chronic lactic acidemia. A second muscle biopsy revealed significantly decreased
      pyruvate oxidation rates and ATP production, but a normal pyruvate dehydrogenase
      complex activity. We suggest that the described mitochondrial dysfunction in our
      patient is secondary to an underlying mutation leading to Joubert syndrome.

PMID- 15944910
TI  - Hashimoto's encephalopathy with selective involvement of the nucleus accumbens: a
      case report.
AB  - Hashimoto's encephalopathy (HE) is an acute or subacute relapsing disorder
      usually affecting euthyroid patients with evidence of autoimmune thyroiditis. The
      neurological manifestations are non-specific, with subacute cognitive impairment,
      movement disorders, generalized seizures, focal neurological symptoms such as
      stroke-like episodes, or psychiatric disturbances. Autoimmune phenomena are
      likely to play an etiological role. Magnetic resonance imaging (MRI) findings are
      usually normal or show non-specific changes. We report the case of an 11-year-old
      girl with autoimmune thyroiditis who presented acutely with a complex
      neuropsychiatric disorder in association with MRI evidence of focal involvement
      of the nucleus accumbens (NA). The NA, a ventral striate nucleus, is part of a
      complex dopaminergic network. Lesions to the NA result in several psychiatric
      symptoms, such as attention-deficit hyperactivity disorders. In this patient, we
      observed alternating phases of stupor and hyperkinetic-anxious behavior, with
      marked instability. The pathogenetic mechanism and the anatomic and functional
      correlations are briefly discussed.

PMID- 15944911
TI  - The eye-of-the-tiger sign is not a reliable disease marker for Hallervorden-Spatz
      syndrome.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN), formerly Hallervorden
      Spatz syndrome, is a rare autosomal recessive disorder characterized by
      extrapyramidal dysfunction as demonstrated by dystonia, rigidity, and
      choreoathetosis. Iron deposition in conjunction with destruction of the globus
      pallidus gives rise to the characteristic eye-of-the-tiger sign in MRI. It has
      been postulated that pantothenate kinase 2 mutations underlying all cases of
      classic Hallervorden-Spatz syndrome are always associated with the eye-of-the
      tiger sign. Here, we report a patient with classic Hallervorden-Spatz syndrome
      and a homozygous pantothenate kinase 2 mutation in whom the initially present eye
      of-the-tiger sign vanished during the course of the disease. Thus, the alleged
      one-to-one correlation between the eye-of-the-tiger sign and the presence of
      pantothenate kinase 2 mutation does not hold true over the course of the disease
      in PKAN.

PMID- 15944912
TI  - Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Report
      of a new case.
AB  - Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) syndrome
      is a new neurodegenerative entity, which was first described by van der Knaap in
      2002 in 7 patients aged from 2 months to 2 years. We describe a new, 42-month-old
      female patient who developed progressive dystonia, spasticity and oculogyric eye
      movements since the age of 3 months. The diagnosis was made by characteristic MRI
      findings including supratentorial hypomyelination and progressive atrophy of
      basal ganglia and cerebellum. Oculogyric eye movements have not been described in
      patients with H-ABC syndrome before. When compared with the normal age-related
      myelination patterns, the degree of hypomyelination increased progressively over
      the time course of 32 months, indicating arrest but not loss of myelination. The
      H-ABC syndrome adds to the differential diagnosis of progressive pyramidal and
      extrapyramidal movement disorders and to the increasing number of genetically
      determined hypomyelination syndromes.

PMID- 15944914
TI  - Localization of annexins I, II, IV and VII in whole prostate sections from
      radical prostatectomy patients.
AB  - Annexins (ANXs) represent a family of calcium and phospholipid binding proteins
      that are involved in several physiological processes e.g. signal transduction,
      cellular differentiation and proliferation. Since they are known to be
      dysregulated in a variety of cancers we investigated the immunolocalization of
      ANXs in whole prostate sections containing benign prostatic epithelium (BPE),
      benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and
      prostate cancer (PCa) in order to evaluate their possible role during
      tumorigenesis. Samples were obtained from 28 patients undergoing radical
      prostatectomy. Gross sections of whole prostates were examined
      immunohistochemically for the distribution of ANX I, II, IV and VII. In BPE all
      ANXs were localized to the cell membranes and the cytoplasm of all gland cells.
      In BPH the immunoreactivity of ANX I and II was restricted to the basal cells of
      glands and expression pattern of ANX IV and VII was similar to BPE. In PIN only
      basal cells expressed ANX II. In PCa ANX II immunoreactivity was absent and weak
      ANX I and ANX IV immunoreactivity was restricted to the cytoplasm of tumor cells.
      ANX VII immunoreactivity was seen in some but not all tumor cells. Since ANX IV
      and VII expression did not show significant changes in PCa compared to non
      neoplastic tissue and PIN an essential role during prostate tumourigenesis seems
      unlikely. In contrast, as progression from PIN to PCa is characterized by a
      reduction of ANX I and II this suggests that downregulation of these proteins
      could represent an important event in prostate carcinogenesis.

PMID- 15944915
TI  - Ferroportin is expressed on the mucous granule membrane of a subpopulation of
      goblet cells in the duodenum of the rat.
AB  - Ferroportin is a basolateral transporter involved in the release of iron from
      cells. In addition to expression on the basolateral membrane of enterocytes,
      ferroportin is also seen on the microvillus membrane. This led us to consider
      that ferroportin might be expressed by other cells of the intestine where it
      contributes to iron metabolism. Ferroportin gene and protein expression in rat
      duodenum was studied by in situ hybridisation and immunohistochemistry,
      respectively in rats with different efficiencies of iron absorption. Ferroportin
      mRNA localised to enterocytes of the villus only. Ferroportin was demonstrated in
      enterocytes and in 30% of goblet cells. In goblet cells it localised to the
      mucous granule membrane. In iron-loaded intestine some goblet cells contained
      iron suggesting that ferroportin may transport iron into the mucous granule where
      it would be lost during discharge of mucous. The finding of ferroportin in iron
      deficient goblet cells also suggests an additional role to iron excretion.

PMID- 15944916
TI  - Glycogen autophagy in the liver and heart of newborn rats. The effects of
      glucagon, adrenalin or rapamycin.
AB  - The effects of glucagon, adrenalin or rapamycin on glycogen autophagy in the
      liver and heart of newborn rats were studied using biochemical determinations and
      electron microscopy. Glucagon or adrenalin increased autophagic activity in the
      hepatocytes and myocardiocytes, glycogen-hydrolyzing acid glucosidase activity in
      the liver and heart and degradation of glycogen inside the autophagic vacuoles.
      Glucagon or adrenalin also increased the maltose-hydrolyzing acid glucosidase
      activity in the liver, but not in the heart. Similar effects were produced in the
      newborn heart by rapamycin. These observations support previous studies
      suggesting that the cellular machinery which controls glycogen autophagy in the
      liver and heart of newborn animals, is regulated by the cyclic AMP and the mTOR
      pathways.

PMID- 15944917
TI  - Cellular distribution of growth hormone-releasing hormone receptor in human
      reproductive system and breast and prostate cancers.
AB  - Growth hormone releasing hormone receptor (GHRH-R) mRNA and protein was first
      localized to the anterior pituitary gland, consequent with the action of its
      ligand on GH synthesis and release. Subsequent studies found GHRH-R also
      expressed in the hypothalamus and in systemic tissues including those of the
      reproductive system. In the present work, we studied the distribution of GHRH-R
      in human reproductive system of males and females by immunohistochemical method.
      GHRH-R immunostaining was localized in male reproductive system: Leydig cells,
      Sertoli and basal germ cells of the seminiferous tubules and prostate secretory
      cells. GHRH-R immunostaining was also demonstrated in the ovary: oocytes,
      follicular cells, granulosa, thecal and corpus luteum cells. Endometrial glands,
      placenta and normal mammary glands also showed GHRH-R immunostaining. Our results
      demonstrate the localization of GHRH-R in the reproductive system, which may
      mediate the direct action of GHRH in these tissues. Moreover, GHRH-R was
      demonstrated in prostate and breast carcinomas, opening a variety of
      possibilities for the use of GHRH antagonists in the treatment of prostatic and
      mammary tumors.

PMID- 15944918
TI  - Consistent lack of CD34-positive stromal cells in the stroma of malignant breast
      lesions.
AB  - To examine the distribution of CD34-positive and ASMA-positive stromal cells in
      various breast lesions, we performed immunohistochemical assays (using a
      streptavidin-biotin immunoperoxidase technique) of tissue specimens, obtained by
      excisional biopsy and partial or total mastectomy, from 62 patients with breast
      lesions. Specimens were obtained from 64 lesions as follows: fibrocystic disease
      (n=12), intraductal papilloma (n=4), fibroadenoma (n=17), invasive lobular
      carcinoma (n=6), invasive ductal carcinoma (n=20) and invasive micropapillary
      carcinoma (n=5). In normal breast tissue (controls), CD34-positive spindle cells
      were abundant in the intralobular stroma, but no ASMA-positive stromal cells were
      identified except myoepithelial cells. Small to large numbers of CD34-positive
      cells were observed in the stroma of 29 of 33 benign diseases. In all invasive
      carcinomas (lobular, ductal and micropapillary), no CD34-positive stromal cells
      were observed in the stroma. In the stroma of benign lesions, the number of ASMA
      positive stromal cells was various, but the stroma of all invasive breast cancers
      contained ASMA-positive stromal cells. The present results indicate that
      disappearance of CD34-positive stromal cells consistently occurs in the stroma of
      invasive carcinoma of the breast, irrespective of histological type and may be
      associated with the presence of ASMA-positive stromal cells.

PMID- 15944919
TI  - Thyrotropin-releasing hormone receptor expression in thyroid follicular cells: a
      new paracrine role of C-cells?
AB  - Thyrotropin-releasing hormone (TRH) synthesized in the hypothalamus has the
      capability of inducing the release of thyroid-stimulating hormone (TSH) from the
      anterior pituitary, which in turn stimulates the production of thyroid hormones
      in the thyroid gland. Immunoreactivity for TRH and TRH-like peptides has been
      found in some tissues outside the nervous system, including thyroid. It has been
      demonstrated that thyroid C-cells express authentic TRH, affecting thyroid
      hormone secretion by follicular cells. Therefore, C-cells could have a paracrine
      role in thyroid homeostasis. If this hypothesis is true, follicular cells should
      express TRH receptors (TRH-Rs) for the paracrine modulation carried out by C
      cells. In order to elucidate whether or not C-cell TRH production could act over
      follicular cells modulating thyroid function, we studied TRH-Rs expression in PC
      C13 follicular cells from rat thyroid, by means of immunofluorescence technique
      and RT-PCR analysis. We also investigated the possibility that C-cells present
      TRH-Rs for the autocrine control of its own TRH production. Our results showed
      consistent expression for both receptors, TRH-R1 and TRH-R2, in 6-23 C-cells, and
      only for TRH-R2 in PC C13 follicular cells. Our data provide new evidence for a
      novel intrathyroidal regulatory pathway of thyroid hormone secretion via
      paracrine/autocrine TRH signaling.

PMID- 15944920
TI  - Metalloproteinase expression by control and telomerase immortalized human
      endometrial endothelial cells.
AB  - Vascular endothelial cells play a critical role in the maintenance of endometrial
      homeostasis. Indeed many pathological conditions causing abnormal endometrial
      bleeding including progestin only contraception, hormone replacement therapy,
      endometrial polyps, myomas, hyperplasia and cancer are associated with aberrant
      angiogenesis. Critical to the process of angiogenesis is the breakdown of the
      surrounding tissues by matrix metalloproteases (MMPs). In addition to the cells
      surrounding the endometrial endothelial cells, the endothelial cells themselves
      produce their own panel of MMPs. We now characterize the specific MMPs that are
      expressed by endothelial cells derived from human endometrium. These include MMP
      1, MMP-2 and MMP-10 but not MMP-3. In addition, in order to successfully carry
      out consistent, homogeneous and sufficient numbers of studies we investigated the
      in vitro expression of the MMPs with both freshly isolated, early passaged
      endometrial endothelial cells (HEECs) as well as with newly telomerase
      immortalized HEECs (T-HEECs). The latter were karyotypically normal and expressed
      classic endothelial cell endpoints such as tubulogenesis on matrigel and
      expression of the endothelial cell markers CD-31 (PECAM), von Willebrand's
      factor, and the Tie-2 receptors. The levels of MMP expression as well as that of
      the metalloprotease inhibitors TIMP-1 and TIMP-2 were similar in parent and
      immortalized endothelial cells.

PMID- 15944921
TI  - Immunohistochemical investigation of amyloid beta-protein (Abeta) in the brain of
      aged cats.
AB  - To clarify the immunohistochemical features of amyloid deposits and cerebral
      amyloid angiopathy (CAA), the distribution of the amyloid beta-protein subtypes
      Abeta40, Abeta42, Abeta43 and Abeta precursor protein (APP) were examined in the
      brains of fourteen aged cats (7.5-21 year-old). Two types of plaques were
      detected. The first type was characterized by Ass positive antigenic material and
      detected in the cortical layers of the frontal and parietal lobes of all examined
      cats. The second type was characterized by diffuse positive immune staining
      representing diffuse plaques, which were detected only in the very aged cats (17
      21 years old) and distributed throughout the cortical layers of the parietal
      lobes. Vascular amyloid and the amyloid deposits were strongly positive-stained
      with the antibody Abeta42. APP was exhibited in neurons and axons while the
      staining was stronger in the very aged cats (17-21 years old). Our findings
      suggest that the feline forms a spontaneous model for understanding the early
      changes of normal brain aging and the early stage of amyloid beta-protein
      deposition.

PMID- 15944922
TI  - Expression of muscarinic acetylcholine receptors (M1-, M2-, M3- and M4-type) in
      the neuromuscular junction of the newborn and adult rat.
AB  - Using intracellular recording and immunohistochemistry, we studied the
      presynaptic muscarinic autoreceptor subtypes controlling ACh release in the
      neuromuscular junctions of the newborn (3-6 days postnatal) and adult (30-40
      days) rat. In the Levator auris longus muscles of both newborn and adult rats,
      acetylcholine release was modified by the M1-receptor selective antagonists
      pirenzepine (10 microM) and MT-7 (100 nM) and by the M2-receptor selective
      antagonists methoctramine (1 microM) and AF-DX 116 (10 microM). The M4-receptor
      selective antagonists tropicamide (1 microM) and MT-3 (100 nM) can also modify
      the neurotransmitter release in certain synapses of the newborn muscles. The
      neurotransmitter release was not altered by the M3-receptor selective antagonist
      4-DAMP (1 microM) in the adult or newborn rats. However, we directly demonstrate
      by immunocytochemistry the presence of these receptors in the motor endplates and
      conclude that M1-, M2-, M3- and M4-type muscarinic receptors are present in all
      the neuromuscular junctions of the rat muscle both in newborn and adult animals.
      These receptors may be located in the perisynaptic glial cell as well as at the
      nerve terminals.

PMID- 15944924
TI  - Clinicopathologic and prognostic significance of cyclooxygenase-2 expression in
      endometrial carcinoma.
AB  - BACKGROUND: Endometrial carcinoma is the most common malignancy of the female
      genital tract in the Western world. COX-2 is highly expressed in endometrial
      carcinoma, but there is controversy regarding its clinical role and its possible
      prognostic role. COX-2 expression was determined by immuno-histochemistry and was
      correlated to standard clinico-pathologic variables in a series of primary
      untreated endometrial carcinoma patients. COX-2 as an accurate predictor of the
      disease was also analyzed. METHODS: One-hundred and ten cases of primary
      untreated endometrial carcinoma hosts who were admitted to the Department of
      Obstetrics and Gynecology, University General Hospital of Alexandroupolis, were
      investigated. Immunohistochemistry was performed using rabbit polyclonal
      antiserum against human COX-2. RESULTS: Twenty-eight patients (25.5%) were scored
      as COX-2 positive. A statistically significant association was found between COX
      2 overexpression and FIGO stage (p=0.010). A positive correlation was also found
      with histological grade (p=0.019) and myometrial invasion (p=0.026). No
      significant association was found with histologic type of the tumor (p=0.164).
      COX-2 positive patients had a significant association with sort survival
      (p=0.028). CONCLUSIONS: COX-2 expression is an independent clinicopathologic
      factor and an independent prognostic factor in endometrial carcinoma. It could be
      used to plan treatment modalities for hosts.

PMID- 15944923
TI  - Effects of triple treatment with octreotide, galanin and serotonin on a human
      pancreas cancer cell line in xenografts.
AB  - Human pancreas cancer cells were implanted s.c. in nude mice. After 11 days, the
      mice were divided into two groups of 13. The first group received sterile saline
      solution and the second received triple therapy containing octreotide, galanin
      and serotonin, 40 microg/kg/day as a continuous i.p. infusion via an implanted
      osmotic pump for 14 days. Triple therapy prolonged the survival rate of the mice
      bearing human pancreatic carcinoma. Both the volume and weight of tumours in mice
      given triple therapy were less than in controls (not statistically significant).
      The proliferation index and the labelling index for epidermal growth factor (EGF)
      increased significantly in mice given triple therapy vis-a-vis controls. There
      was no statistically significant difference between control and treated tumours
      as regards, apoptotic index, necrosis, or number of tumour blood vessels. The
      increased survival rate was attributed to the reduced tumour load, since both
      weight and volume were reduced. It is most probable that octreotide was the
      responsible agent. Further investigation with single and double combinations of
      octreotide, galanin and serotonin are needed to identify the cause of increased
      cell proliferation in tumours subjected to these bioactive substances.
      Identifying the agent(s) inducing pancreatic cancer cell proliferation may be
      useful in combining a new treatment, as antagonists to these bioactive substances
      are available.

PMID- 15944925
TI  - Immunohistochemical localization of senescence marker protein-30 (SMP30) in the
      submandibular gland and ultrastructural changes of the granular duct cells in
      SMP30 knockout mice.
AB  - Senescence Marker Protein-30 (SMP30) is a calcium-regulating protein that
      decreases in an androgen-independent manner as aging occurs. An enzyme-labeled
      antibody technique has demonstrated that SMP30 localized to the ducts (granular,
      intercalated, and striated ducts) of mouse submandibular glands.
      Immunoelectronmicroscopy demonstrated that the granular duct cells were strongly
      positive for SMP30, but that pillar cells in the granular duct were negative for
      the protein. In SMP30-knockout (KO) mice, the granular ducts were smaller in
      diameter. Swelling of mitochondria in the granular duct cells was observed;
      however, this phenomenon was not observed in the pillar cells. After
      administration of alpha-isoproterenol, a beta-adrenergic stimulant, a large
      numbers of small secretory granules were present in the granular duct cells and
      an expansion of the rough endoplasmic reticulum in SMP30-wild type (WT) mice; in
      contrast, little change was observed in SMP30-KO mice. These results suggest that
      SMP30 may be closely related to a signal transduction pathway in the granular
      duct cells of submandibular glands.

PMID- 15944926
TI  - Karyotypic analysis of adult pluripotent stem cells.
AB  - Three categories of precursor cells have been identified in postnatal mammals:
      tissue-committed progenitor cells, germ layer lineage-committed stem cells and
      lineage-uncommitted pluripotent stem cells. Progenitor cells are the immediate
      precursors of differentiated tissues. Germ layer lineage stem cells can be
      induced to form multiple cell types belonging to their respective ectodermal,
      mesodermal, and endodermal embryological lineages. Pluripotent stem cells will
      form somatic cell types from all three primary germ layer lineages. Progenitor
      cells demonstrate a finite life span before replicative senescence and cell death
      occur. Both germ layer lineage stem cells and pluripotent stem cells are
      telomerase positive and display extensive capabilities for self-renewal. Stem
      cells which undergo such extensive replication have the potential for undergoing
      mutations that may subsequently alter cellular functions. Gross mutations in the
      genome may be visualized as chromosomal aneuploidy and/or chromosomes that appear
      aberrant. This study was designed to determine whether any gross genomic
      mutations occurred within the adult pluripotent stem cells. Karyotypic analysis
      was performed using pluripotent stem cells purified from adult male rats using
      established procedures. Giemsa Banding was used in conjunction with light
      microscopy to visualize metaphase chromosome spreads. To date over 800 metaphase
      spreads have been analyzed. We found that the metaphase spreads averaged 42
      chromosomes and concluded that these pluripotent stem cells isolated from adult
      rats have a normal karyotype.

PMID- 15944927
TI  - Unusual circular annulate lamellae in hepatocytes of Torpedo marmorata.
AB  - This report describes an unusual morphology of annulate lamellae (AL) in the
      hepatocytes of Torpedo marmorata Risso. These Als and fragments are detected
      amidst the main glycogen and lipid deposits. AL cisterns are circumscribed by
      parts of the smooth endoplasmic reticulum. Based on the finding of these unusual
      annular ALs, accompanied by other subcellular lesions such as a number of
      membranous whorls and altered mitochondria. These findings can concur and support
      other authors' observations suggesting that these adult hepatocytes transient
      changes reflect that this species could be exposed to local, natural or likely
      human coastal seabed pollutants.

PMID- 15944928
TI  - Simultaneous bilateral breast carcinoma: Histopathological characteristics and
      CD44/catenin-cadherin profile.
AB  - AIMS: Family history of breast carcinoma, multicentric tumor foci in one breast,
      and in situ lobular carcinoma increase the risk of bilateral breast cancer (BBC),
      synchronous or metachronous. Synchronous tumors are designated as simultaneous
      breast carcinoma if they appear at the same time. The CD44 family and
      cadherin/catenin immunophenotype of this group of BBCs has not yet been
      evaluated. The aim of this study was to compare clinicopathological
      characteristics and immunohistochemical profiles of simultaneous BBC and
      corresponding lymph node metastases in eight patients. METHODS AND RESULTS: In
      toto 15 primary and 9 metastatic tumors were evaluated. The expression of CD44
      variant isoforms, beta-catenin, E, P and N-cadherin were evaluated by
      immunohistochemistry. Rare types of breast carcinoma were frequent in this group
      of patients. There were 6 pleomorphic lobular, 5 invasive ductal of usual type, 3
      atypical medullary carcinomas, 2 mucinous and one invasive micropapillary
      carcinoma. The expression CD44v6 was most frequent, followed by CD44v3-10,
      CD44v5, and CD44v3. CD44v4 was generally not expressed. E-cadherin was expressed
      in 80% primary tumors, 40% expressed N-cadherin, and 66% expressed P-cadherin.
      CONCLUSIONS: Generally, simultaneous carcinomas had different morphology and
      different immunophenotype. Each primary tumor was more similar to its
      corresponding metastatic tumor than to the contralateral primary tumor.

PMID- 15944929
TI  - Sclerotic fibroma-like dermatofibroma: an uncommon distinctive variant of
      dermatofibroma.
AB  - Dermatofibroma (DF) is a common benign cutaneous tumor with many variants based
      on alterations in the morphology and composition of its diverse elements. One
      very infrequent type is sclerotic fibroma-like DF (SF-DF). We report 7 new cases
      of SF-DF. In addition, their main clinicopathological and immunohistochemical
      features were compared with 14 unselected common DFs and with 3 sclerotic
      fibromas (SFs). Microscopically, the 7 cases of SF-DFs showed an unencapsulated,
      well-circumscribed, hypocellular central nodule with thick collagen bundles
      arranged in a storiform pattern with prominent clefts. The overlying epidermis
      was attenuated. The periphery of this nodule was more cellular with
      histopathologic features of common DF. The 7 SF-DFs patients were 4 women and 3
      men with a mean (+/-SD) age of 44.8 (+/-15.5) years. These 7 patients were
      younger than those suffering from SFs [71.0 (+/-17.3) years; (p=0.04)] and older
      than those presenting common DFs [30.5 (+/-12.3) years; (p=0.03)].
      Immunohistochemically, spindle cells in all 7 SF-DFs were negative for CD34 and
      CD99. On the contrary, the 3 cases of SF were positive for CD34 and CD99. All of
      the common DFs were negative for CD34 and only 4 (28.6%) of them were positive
      for CD99. In conclusion, SF-DF is an uncommon variant of DF with similar
      clinicopathological and immunohistochemical features. SF-DF shares certain
      histopathologic features with SF but they are immunophenotypically different.
      Therefore, both entities should be differentiated.

PMID- 15944930
TI  - Immunohistochemical analyses on albumin and immunoglobulin in acute hypertensive
      mouse kidneys by "in vivo cryotechnique".
AB  - The purpose of this study is to visualize topographical changes of serum
      proteins, albumin and immunoglobulin, passing through mouse glomerular capillary
      loops and their reabsorption in renal proximal tubules by immunohistochemistry in
      combination with our "in vivo cryotechnique". The "in vivo cryotechnique" was
      performed on left mouse kidneys under normotensive, experimentally acute
      hypertensive and heart-arrest conditions. The cryofixed tissues by the technique
      were routinely processed for freeze-substitution. Serial deparaffinized sections
      were stained with hematoxylin-eosine and immunostained with anti-mouse albumin,
      immunoglobulin G (IgG), kappa or lambda light chain and IgG1 heavy chain
      antibodies. Under the normotensive and heart-arrest conditions, albumin and IgG
      were clearly immunolocalized in blood vessels and slightly in apical cytoplasmic
      parts of some proximal tubules. Under the acute hypertensive condition, the
      albumin and kappa or lambda light chains, but not IgG1 heavy chain, were strongly
      immunolocalized in the apical cytoplasm of almost all proximal tubules. This
      study is the first in vivo visualization for glomerular passage of serum proteins
      and their transtubular absorption. Thus, the "in vivo cryotechnique" with freeze
      substitution can be used for clarifying not only the functional morphology of
      living animal cells, but also in situ immunohistochemical localization of their
      components.

PMID- 15944931
TI  - Detection of transforming growth factor-alpha and epidermal growth factor
      receptor mRNA and immunohistochemical localization of the corresponding proteins
      in the canine uterus during the estrous cycle.
AB  - Uterine expression of the epidermal growth factor (EGF) family of growth factors
      has not been studied in the dog. The present study looks at the presence of mRNA
      transcripts and immunohistochemical localization for transforming growth factor
      alpha (TGF-alpha), which is the potent EGF family member, and for EGF receptor
      (EGF-R) in the canine uterus during the estrous cycle. The reverse transcriptase
      polymerase chain reaction together with sequencing of the products confirmed the
      presence of their mRNA transcripts in the endometrium throughout the estrous
      cycle. Immunohistochemical analysis found clear positive staining for TGF-alpha
      and EGF-R in the luminal and glandular epithelia at proestrus and estrus.
      Immunoreactivity decreased at the early stage of diestrus. In the mid stage of
      diestrus, clear staining for TGF-alpha was again found in the glands of the
      luminal region, and staining for EGF-R was observed in all glands. Very little
      staining was seen at anestrus for either TGF-alpha or EGF-R. These results
      suggest that TGF-alpha expressed in the uterus may be involved in regulating
      growth, differentiation and regression in the endometrial epithelial cells during
      the estrous cycle in the dog.

PMID- 15944932
TI  - Role of prostaglandin E2 receptor subtypes in ovarian follicle growth in the rat
      in vivo. Correlation with interleukin-8 and neutrophils.
AB  - This study was conducted to elucidate the role of three of prostaglandin E2
      (PGE2) receptor subtype (EP2, EP3, and EP4) agonists in the process of follicular
      growth. The influence of these agonists on ovarian expression of intimately
      related factors to follicle development (neutrophils and interleukin-8 (IL-8))
      was also investigated. Immature female Wistar rats were injected once with these
      agonists and killed 48 hours later. Another group of rats were injected pregnant
      mare serum gonadotrophin. For evaluation of follicle growth, morphometric
      assessment of antral and ovulatory follicles was performed in serial ovarian
      sections. The study demonstrated that, EP2 and EP4 agonists showed the maximum
      follicle counts and diameters versus the control. EP2 and EP4 agonists mimicked
      PMSG induced follicle growth. Injection of the three agonists induced neutrophil
      infiltration into theca layer. EP4 agonist showed the most intense ovarian
      neutrophil accumulation. In addition, dense ovarian IL-8 expression was observed
      only after EP4 agonist injection. CONCLUSIONS: Our data suggests that: 1) EP2 and
      EP4 receptors are the key PGE2 receptors engaged in follicle growth. 2) Ovarian
      IL-8 expression and neutrophil infiltration are chiefly mediated via the EP4
      receptor. EP2 and EP4 receptor agonists may be candidates for promising reagents
      that induce follicle maturation in clinical or agricultural fields. This
      knowledge could provide numerous targets for manipulation of fertility.

PMID- 15944933
TI  - Chronic alpha1-adrenoreceptor blockade produces age-dependent changes in rat
      thymus structure and thymocyte differentiation.
AB  - In order to examine the influence of chronic alpha1-adrenergic receptor (alpha1
      AR) blockade on the thymus structure and T-cell maturation, peripubertal and
      adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15
      consecutive days. Thymic structure and phenotypic characteristics of the
      thymocytes were assessed by stereological and flow cytometry analysis,
      respectively. In immature rats, treatment with urapidil reduced the body weight
      gain and, affecting the volume of cortical compartment and its cellularity
      decreased the organ size and the total number of thymocytes compared to age
      matched saline-injected controls. The percentage of CD4+8- single positive (SP)
      thymocytes was decreased, while that of CD4-8+ was increased suggesting, most
      likely, a disregulation in final steps of the positively selected cells
      maturation. However, alpha1-AR blockade in adult rats increased the thymus weight
      as a consequence of increase in the cortical size and cellularity. The increased
      percentage of most immature CD4-8- double negative (DN) cells associated with
      decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests
      a decelerated transition from DN to DP stage of T-cell development. As in
      immature rats, the treatment in adult rats evoked changes in the relative numbers
      of SP cells, but contrary to immature animals, favoring the maturation of CD4+8-
      over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of
      alpha1-ARs affects both the thymus structure and thymocyte differentiation, ii)
      these effects are age-dependent, pointing out to pharmacological manipulation of
      alpha1-AR-mediated signaling as potential means for modulation of the intrathymic
      T-cell maturation.

PMID- 15944934
TI  - Decreased density of beta1-adrenergic receptors in preneoplastic and neoplastic
      liver lesions of F344 rats.
AB  - There is some evidence that rodent hepatocarcinogenesis is accompanied by changes
      in the adrenergic responsiveness of liver cells to catecholamines. In this study,
      immunohistochemical expression of beta1-adrenergic receptors (beta1-ARs) has been
      examined in spontaneous and chemically induced preneoplastic and neoplastic liver
      lesions of female and male Fischer 344 rats. An antibody specific for beta1-AR
      subtype was used. The study was carried out on archival formalin-fixed and
      paraffin-embedded livers from rats used in a previous study of
      hepatocarcinogenesis. One control group given distilled water by gavage, and two
      experimental groups, one initiated with a single dose of diethylnitrosamine (DEN)
      and one initiated with DEN and continuously treated with phenobarbital (PB) were
      examined. Rats were sacrificed after 2, 4, 8 and 21 months of experimentation.
      All types of liver putative preneoplastic lesions examined (basophilic, glycogen
      retaining, or mixed cell foci) show a lower density of beta1-ARs than the
      surrounding normal liver parenchyma, either in control and in DEN-treated or
      DEN+PB-treated rats. No immunostaining is detectable in several altered cell
      foci. Hepatocellular adenomas and hepatocellular carcinomas also show a very low
      density of beta1-ARs, extensive areas completely devoid of beta1-ARs being
      mingled with areas showing a weak immunostaining.

PMID- 15944935
TI  - Histopathologic features of the vagus nerve after electrical stimulation in
      swine.
AB  - This paper describes the histological features of the vagus nerve after its
      stimulation with an electrostimulation system that is being developed for morbid
      obesity treatment. An electrostimulation system was implanted laparoscopically
      around the ventral vagal trunk of five Large White female pigs (49.63+/-1.94
      kg.). Vagal nerve stimulation was performed by continuous constant voltage
      current pulses. Thoracic samples of both ventral and dorsal vagal trunks were
      obtained thoracoscopically one month after implantation. Animals were sacrificed
      one month after thoracoscopic vaguectomy. Tissue samples were then harvested from
      the vagal nerve at the implantation site, 1cm cranial to it, thoracic portion of
      ventral and dorsal vagal trunks, sub-diaphragmatic dorsal vagal trunk, left and
      right vagus nerves. Specimens were analysed with light microscope. The severity
      of the lesions was graded from 0 to 4 (0: no lesion, 1: mild, 2: moderate, 3:
      severe and 4: extremely severe), taking into account fibrosis, vascularization,
      necrosis, fiber degeneration and inflammation. Electrode implantation resulted in
      thickened epineurium and endoneural connective tissue. The greatest lesion score
      was evidenced at the leads implantation site in the ventral vagal trunk, followed
      by, in order of decreasing lesion severity, left vagus nerve, thoracic portion of
      ventral vagal trunk, subdiaphragmatic dorsal vagal trunk, thoracic portion of
      dorsal vagal trunk and right vagus nerve. The stimulation device used in this
      study caused connective tissue growth, greatest in the samples located closer to
      the implantation site. However, there was no sign of altered vascularization in
      any studied specimen.

PMID- 15944936
TI  - Detection of CX3CR1 single nucleotide polymorphism and expression on archived
      eyes with age-related macular degeneration.
AB  - There is a significant genetic component in age-related macular degeneration
      (AMD). CX3CR1, which encodes the fractalkine (chemokine, CX3CL1) receptor, has
      two single nucleotide polymorphisms (SNPs): V249I and T280M. These SNPs are
      correlated with other aged-related diseases such as atherosclerosis. We have
      reported an association of CX3CR1 SNP and AMD. In this study we examined CX3CR1
      SNP frequencies and protein expression on archived sections of AMD and normal
      eyes. We microdissected non-retinal, peripheral retinal and macular cells from
      archived slides of eyes of AMD patients and normal subjects. CX3CR1 SNP typing
      was conducted by PCR and restriction fragment length polymorphism analysis.
      CX3CR1 transcripts from retinal cells were also measured using RT-PCR. CX3CR1
      protein expression was evaluated using avidin-biotin complex
      immunohistochemistry. We successfully extracted DNA from 32/40 AMD cases and 2/2
      normal eyes. Among the 32 AMD cases, 18 had neovascular AMD and 14 had non
      neovascular AMD. The M280 allele was detected in 19/64 (32 cases x2) with a
      frequency of 29.7%, which was significantly higher as compared to the frequency
      in the normal population (11.2%). We detected CX3CR1 expression in the various
      retinal cells. CX3CR1 transcript and protein levels were diminished in the
      macular lesions. This study successfully analyzed CX3CR1 SNP and transcript
      expression in microdissected cells from archived paraffin fixed slides. Our data
      suggest that the M280 allele, a SNP resulting in aberrant CX3CR1 and CX3CL1
      interaction, as well as lowered expression of macular CX3CR1, may contribute to
      the development of AMD.

PMID- 15944937
TI  - Antigenic profile of human bronchial gland.
AB  - Bronchial glands have been regarded as modified salivary glands. It is well known
      that there no previous reviews concerning the antigenic profile of the bronchial
      wall. The aim of this study is a systematic survey of the antigenic profile and
      to describe the histology of normal human bronchial glands. Six formalin-fixed,
      paraffin-embedded surgical specimens were studied using a panel of 22 polyclonal
      and monoclonal antibodies by the avidin-biotin-peroxidase method. Bronchial
      glands disclosed a tubuloacinar structure. The smallest ducts intercalated
      originated from a cluster of secretory acini and converge to form an excretory
      duct. No striated duct was observed. Acinar united is composed by mucous, serous
      and mixed units. Myoepithelial cells are found in relation to the intercalated
      ducts and secretory acinis. Secretory cells of bronchial glands reacted strongly
      with cytokeratin AE1 and moderately for CK7, CK18. Additionally, serous acinar
      cells reacted with AE3, CK19, CK5/6/8/18, CK8/18/19, and Leu7. Myoepithelial
      cells reacted strongly with a-smooth muscle actin, CD10 and CK34betaE12. Ductal
      system cells differed from acinar secretory cells in expressing CK34betaE12 and
      HSP27. In conclusion, the detailed knowledge of the immunohistochemical
      reactivities of normal cell types of normal human bronchial glands will prove
      useful in studies of bronchial pathology, especially of neoplastic processes.

PMID- 15944938
TI  - Thymidylate synthase predicts for clinical outcome in invasive breast cancer.
AB  - Thymidylate synthase (TS) is a major target of 5-fluorouracil (5-FU) and
      dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme in the
      degradation of 5-FU. Whether TS or DPD could be used as valuable parameters for 5
      FU sensitivity in clinical patients are largely unknown. We analyzed TS and DPD
      expression in breast carcinomas to evaluate the clinicopathological significance
      of these enzymes in patients with invasive breast cancer receiving 5-FU-based
      chemotherapy. A total of 197 patients with invasive ductal carcinoma were
      included in our study. Both the TS and DPD expression were analyzed using
      immunohistochemical method for all the surgical samples. Sixty-three out of 197
      (31.97%) patients are positive for TS expression, and 77 out of 197 (39.09%)
      patients are positive for DPD expression. TS expression was not correlated with
      DPD expression. Patients with TS-positivity had aggressive phenotype including
      large tumor size, low differentiation and nodal metastasis. DPD expression is not
      related with phenotype or prognosis. Multivariate analysis demonstrated that TS
      expression was an independent prognostic factor for both disease-free and overall
      survival. The current study demonstrated that TS but not DPD expression was
      associated with both progression and prognosis in breast cancer receiving 5-FU
      based chemotherapy. TS expression in the primary tumor might be useful as a
      predictive parameter for the efficacy of 5-FU-based chemotherapy for breast
      cancer.

PMID- 15944940
TI  - Muscle-derived stem cells in tissue engineering: defining cell properties
      suitable for construct design.
AB  - The terms construct or tissue equivalent refer to neotissue produced by tissue
      engineering techniques. The elements forming the construct are scaffolds on which
      cells are "recreated" to form an engineered-tissue sensitive to certain cell
      signals. The ability of the cells to expand and differentiate on the scaffold is
      determined by properties such as fixation, adhesion, proliferation and migration.
      Among the cell types that seem to be most promising for designing constructs are
      tissue-residing, or adult, stem cells, which show two main features: a capacity
      to differentiate into many cell lineages and the power of self-renewal. These
      features make them good candidates for cell replacement therapies. Here, we
      report the identification, isolation and culture of muscle stem cells aimed at
      establishing the ideal culture in terms of defining when the cultured cell
      population would show optimal characteristics for transfer to the scaffold to
      obtain a particular construct. Stem cells harvested from the dorsal muscle of
      white New Zealand rabbits were cultured in vitro and characterized 5 to 14 days
      after the start of culture. Fibroblasts obtained from the same experimental
      animal served as controls. The stem cells were examined by light and scanning
      electron microscopy. For stem cell identification, we used the antibodies anti-m
      cadherin, anti-CD34 and anti-Myf-5. The markers of muscle differentiation used
      were: anti-vimentin, anti-alpha-actin, anti-desmin and anti-myosin. The
      expression profiles of the different markers of muscle differentiation and
      TGFbeta1 in the cell cultures were confirmed by Western blotting. Proliferation
      rates were determined by monitoring tritiated thymidine incorporation. The
      thymidine incorporation rate was substantially higher for the population of
      undifferentiated cells than for control fibroblasts obtained from the same
      animal. During the first five days of culture, most cells were negative for all
      the markers examined, with the exception of m-cadherin, CD34 and Myf-5, although
      discrete signs of vimentin expression started to emerge. After 14 days of
      culture, the adult stem cells showed vimentin (94.2%) and desmin (33.8%)
      expression yet scarce labeling for myosin (16.2%) and alpha-actin (8.3%). Control
      fibroblasts showed intense labeling for vimentin (99.3%) and alpha-actin (62.2%),
      while less than 2% of the population expressed myosin (0.9%) and desmin (1.6%).
      After two weeks of culture, muscle-derived stem cells show good proliferative and
      adhesion properties as they initiate differentiation. These conditions seem ideal
      for obtaining the desired construct.

PMID- 15944939
TI  - Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis
      following allogeneic stem cell transplantation.
AB  - Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow
      (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral
      stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore,
      an immunohistochemical and morphometric study was performed on BM biopsies in 20
      patients before and at standardized intervals (days 30 through 384) following
      SCT. In responding patients, a total regression of the pretransplant increased
      fibrosis was completed in the posttransplant period after about six months, while
      the extent of osteosclerosis did not change significantly during observation
      time. The quantity of CD61+ megakaryocytes including precursors was strikingly
      variable after SCT and, by using planimetric methods, atypical microforms
      exhibiting a dysplastic aspect could be demonstrated. These anomalies may be
      responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were
      increased before transplantation, however, their number declined rapidly to
      normal values in responding patients. Nucleated erythroid precursors revealed a
      decreased amount before and after SCT accounting for anemia. Large clusters of
      this cell lineage indicated an initial hematopoietic reconstitution comparable
      with the expansion of the neutrophil granulopoiesis. Proliferative activity and
      apoptosis showed an increase until one year after SCT that implied a still
      regenerating hematopoiesis in keeping with an enhanced cell turnover.

PMID- 15944941
TI  - Labeling of adult stem cells for in vivo-application in the human heart.
AB  - Tissue regeneration with human hematopoietic or mesenchymal stem cells has become
      a fashionable research topic. In cardiology, intracoronary injection of adult
      stem cells has already been used for the treatment of human myocardial infarction
      and ischemic cardiomyopathy. The experimental background of such therapies,
      however, i.e. the potential of adult stem cells to regenerate myocardium through
      "transdifferentiation" of hematopoietic or mesenchymal stem cells into
      cardiomyocytes described in animal models, has recently been challenged by other
      experimental data. Nonetheless, clinical trials are continuing. This may be due
      to the fact that, in open-labeled pilot trials, a benefit of intracoronary
      injection of adult stem cells for the treatment of myocardial infarction has been
      described. As pilot trials may overemphasize the beneficial effects of
      intracoronary injection of bone marrow stem cells, controlled double-blinded
      randomised multicenter studies are warranted. Furthermore, a careful
      characterization of the cells involved in the proposed cardiac repair as well as
      in vivo-monitoring of such cells following intracoronary injection in humans
      might help to answer many essential questions linked to this important research
      topic. The latter requires biocompatible labeling. This review focuses on the
      technologies available for stem cell labeling and summarizes the arguments and
      contra-arguments to use these labeling technologies for application in humans.

PMID- 15944942
TI  - Chemokines and their receptors in disease.
AB  - Chemokines are a family of structurally related low molecular weight (8-10 kDa)
      proteins that are important for the organization of tissues during development
      and regulate cell motility and localization both during development and in the
      adult. In the adult, this function is predominantly related to the trafficking of
      leukocytes, although more recently the impact of these molecules on other cell
      types has become apparent. Chemokines mediate their effects by binding seven
      transmembrane, G-protein coupled, receptors. In addition to their primary role in
      regulating cell motility, they can also influence cell survival and
      proliferation. Antagonists for a number of chemokine receptor have been
      developed, raising the possibility of interfering with chemokine function as a
      therapeutic tool. This review focuses on the emerging roles for chemokines in
      normal physiology and disease.

PMID- 15944943
TI  - The "early birds": natural IgM antibodies and immune surveillance.
AB  - Precancerous epithelial lesions are sites of uncontrolled cellular proliferation
      generated by irreversible genetic alterations. Not all of those lesions progress
      to invasive cancer, some may even regress, but the early detection of abnormal
      cells can be crucial for patient survival. Immune surveillance mechanisms are
      responsible for the removal of transformed cells and antibodies play an important
      role in these immune processes. In the past, analysis of the immunoglobuline
      repertoire has focused mainly on xenoimmunizations or the investigation of cancer
      patient immunity. The human hybridoma technology (Trioma technique) offers the
      unique possibility to study the humoral immunity of healthy people. Using this
      technique a series of tumor-binding antibodies could be isolated which all have
      several features in common: they are germ-line coded IgM antibodies, they
      predominantly bind to carbohydrates on post-transcriptionally modified antigens,
      they induce apoptosis and, most importantly, they detect not only malignant cells
      but also precursor stages. These data demonstrate that the body has a
      comprehensive defense system against malignant cells based on the production of
      natural antibodies.

PMID- 15944944
TI  - Immunological and molecular aspects of liver fibrosis in chronic hepatitis C
      virus infection.
AB  - Chronic C hepatitis represents a major health problem worldwide, mainly because
      progression of the tissue damage leads to the development of cirrhosis and
      hepatocellular carcinoma. In this review we discuss the molecular mechanisms
      underlying the development of liver fibrosis. In particular we consider some
      immunologic aspects that regulate the interaction between HCV and the host immune
      defense. Reflections are made about the roles played by the host capacity to
      respond to the viral infection during therapy and the consequences of the
      deposition of extracellular matrix (ECM) proteins leading to the development of
      fibrosis. The involvement of inflammatory cytokines in regulating the proteolytic
      remodeling of the liver and the ECM turn-over is essential for the activation of
      hepatic stellate cells (HSCs), that have an important role in the progression of
      liver fibrosis. Finally, we analyze one of the aspects involved in the activation
      of the HSCs, namely the proteolytic remodeling of the surrounding environment.

PMID- 15944945
TI  - Bruton's Tyrosine Kinase is involved in innate and adaptive immunity.
AB  - Btk is a cytoplasmic tyrosine kinase, which is mainly involved in B cell receptor
      signalling. Gene targeting experiments revealed that Btk is important for B cell
      development and function. However, Btk is not only expressed in B cells, but also
      in most other haematopoietic lineages except for T cells and plasma cells.
      Recently we found that Btk is involved in Toll-like receptor signalling. Toll
      like receptors play an important role in innate immunity. They are highly
      expressed on mast cells, macrophages and dendritic cells, which are essential for
      the recognition and consequently for the elimination of microbial pathogens.
      Therefore Btk might play an important role for the function of immunocompetent
      cells of innate as well as adaptive immunity.

PMID- 15944946
TI  - Role of oxidative damage in the pathogenesis of viral infections of the nervous
      system.
AB  - Oxidative stress, primarily due to increased generation of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), is a feature of many viral
      infections. ROS and RNS modulate the permissiveness of cells to viral
      replication, regulate host inflammatory and immune responses, and cause oxidative
      damage to both host tissue and progeny virus. The lipid-rich nervous system is
      particularly susceptible to lipid peroxidation, an autocatalytic process that
      damages lipid-containing structures and yields reactive by-products, which can
      covalently modify and damage cellular macromolecules. Oxidative injury is a
      component of acute encephalitis caused by herpes simplex virus type 1 and
      reovirus, neurodegenerative disease caused by human immunodeficiency virus and
      murine leukemia virus, and subacute sclerosing panencephalitis caused by measles
      virus. The extent to which oxidative damage plays a beneficial role for the host
      by limiting viral replication is largely unknown. An enhanced understanding of
      the role of oxidative damage in viral infections of the nervous system may lead
      to therapeutic strategies to reduce tissue damage during viral infection without
      impeding the host antiviral response.

PMID- 15944947
TI  - New aspects on the role of lipoxygenases in cancer progression.
AB  - The Lipoxygenases (LOXs) are a class of enzymes that convert arachidonic,
      linoleic, and other polyunsaturated fatty acid into biologically active
      metabolites involved in the inflammatory and immune responses. Recent evidences
      indicate that LOXs and the signaling pathways that are involved in their
      activation are also important for carcinogenesis and tumor progression. LOXs
      should therefore receive as much attention from cancer researchers as it has
      already from immunologists. In this article, we will review some evidence that
      the LOXs pathways affect several aspects of lung, pancreatic and prostate cancer
      progression. Moreover, we discuss how this new perspective on the roles of LOXs
      and their metabolites can have important implications to cancer therapy.

PMID- 15944948
TI  - Nuclear reprogramming and adult stem cell potential.
AB  - Cell-based therapy may represent a new strategy to treat a vast array of clinical
      disorders including neurodegenerative diseases. Recent observations indicate that
      adult somatic stem cells have the capacity to contribute to the regeneration of
      different tissues, suggesting that differentiative restrictions are not
      completely irreversible and can be reprogrammed. Cell fusion might account for
      some changed phenotype of adult cells but it seems to be biologically irrelevant
      for its extreme rarity. Other experimental evidences are compatible with the
      hypothesis of wide multipotency of well-defined stem cell populations, but also
      with transdifferentiation and/or dedifferentiation. Further studies on nuclear
      reprogramming mechanisms are necessary to fulfil the promise for developing
      autologous cellular therapies.

PMID- 15944949
TI  - Hypoxic adaptation of the rat carotid body.
AB  - Three types of hypoxia with different levels of carbon dioxide (hypocapnic,
      isocapnic, and hypercapnic hypoxia) have been called systemic hypoxia. The
      systemic hypoxic carotid bodies were enlarged several fold, but the degree of
      enlargement was different for each. The mean short and long axes of hypocapnic
      and isocapnic hypoxic carotid bodies were 1.6 (short axis) and 1.8-1.9 (long
      axis) times larger than normoxic control carotid bodies, respectively. Those of
      hypercapnic hypoxic carotid bodies were 1.2 (short axis) and 1.5 (long axis)
      times larger than controls, respectively. The rate of enlargement in hypercapnic
      hypoxic carotid bodies was lower than in hypocapnic and isocapnic hypoxic carotid
      bodies. The rate of vascular enlargement in hypercapnic hypoxic carotid bodies
      was also smaller than in hypocapnic and isocapnic hypoxic carotid bodies. Thus,
      the enlargement of hypoxic carotid bodies is mainly due to vascular dilation.
      Different levels of arterial CO2 tension change the peptidergic innervation
      during chronically hypoxic exposure. The characteristic vascular arrangement was
      under the control of altered peptidergic innervation. During the course of
      hypoxic adaptation, the enlargement of the carotid bodies with vascular expansion
      began soon after the start of hypoxic exposure. During the course of recovery,
      the shrinking of the carotid bodies with vascular contraction also started at a
      relatively early period after the termination of chronic hypoxia. These processes
      during the course of hypoxic adaptation and during the course of recovery were
      under the control of peptidergic innervation. These findings may provide a
      standard for further studies of hypoxic carotid bodies.

PMID- 15944950
TI  - Novel oncogene HCCR: its diagnostic and therapeutic implications for cancer.
AB  - Identification of robust diagnostic and therapeutic target molecules for human
      malignancy is still an important issue. If we identify novel proteins which play
      a stem-line role for cellular transformation or aggravation of malignancy, it
      could give us a clue to diagnose a tumor in an earlier stage and to develop more
      reliable therapeutic tools. For this purpose, we have screened abnormally
      expressed genes in various human cancers by differential display RT-PCR. One of
      the overexpressed genes was a human cervical cancer oncogene (HCCR). HCCR was not
      only identified in cervical cancer tissues, but also found to be overexpressed in
      various human malignancies such as leukemia/lymphoma, breast, kidney, stomach,
      colon, liver and ovarian cancer. This molecule appeared to be a negative
      regulator of p53. In this paper, we discuss the biological functions of HCCR
      molecules and its implications for early diagnosis and future development of
      therapeutic devices of cancer.

PMID- 15944951
TI  - The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase
      receptors and the consequences for therapeutic approaches.
AB  - The HER family of receptor tyrosine kinase couples binding of extracellular
      growth factor ligands to intracellular signal transduction pathways, contributing
      in this fashion to the ability of the cell to respond correctly to its
      environment. The HER family and its ligands are critically involved in the
      carcinogenesis of the mammary gland. Abnormal function of the members of HER
      family resulting in receptor hyper-activation (due to gene amplification, protein
      overexpression or abnormal transcriptional regulation) has been linked with
      breast cancer prognosis. It is also extensively studied as the predictive factor
      and target for therapy. There are clinical indications supporting the concept
      that none of the receptors: EGFR, HER2, HER3 and HER4 can be considered as the
      stand-alone receptor in breast cancer development and clinical course of the
      disease. There is a growing body of evidence that cooperation between them
      contributes to more aggressive tumor phenotype and influences the response to
      therapy. This underlines the importance of quantification of all HER family
      members and indicates the urgent need for implementation of methods that can
      efficiently and reliably examine four HER receptors as a whole panel in breast
      cancer patients.

PMID- 15944952
TI  - Inflammatory myofibroblastic tumor of the breast.
AB  - Three patients developed firm, mobile, nontender masses in their breasts. Two
      were discovered by the patients and one after mammography. Macroscopically, the
      nodules were firm, circumscribed, yellow on cut sections, and composed of
      interlacing cytologically bland spindle cells admixed with chronic inflammatory
      cells, the latter predominantly of lymphocytes and plasma cells.
      Immunohistochemistry yielded strong smooth-muscle actin reactivity within the
      spindle cells; 2 lesions were negative for pankeratin, 1 was focally and weakly
      positive. No lesions were positive for anaplastic lymphoma kinase-1, desmin, S
      100, CD34, CD21, or CD35. In each case, a diagnosis of inflammatory
      myofibroblastic tumor was made (aka, inflammatory pseudotumor). After
      conservative excision with apparently negative margins, there have been no
      recurrences, except in one patient who developed a recurrence after 3 months. The
      latter recurrence was managed successfully with a second excision. We report
      these patients to emphasize the diagnostic features of inflammatory
      myofibroblastic tumor of the breast and discuss how they can be distinguished
      from other spindle-cell breast lesions with which they can be confused,
      especially spindle-cell carcinoma.

PMID- 15944953
TI  - Evaluation of basement membrane status in aggressive skin carcinomas with skull
      base invasion: a case-control study.
AB  - Some skin carcinomas may be very aggressive. Breached of basement membrane (BM)
      has been in some situations associated with tumor aggressiveness. In this study,
      the status of BM in invasion was evaluated in basal cell carcinomas (BCCs) and
      squamous cell carcinomas (SCCs) with skull base invasion, and it was compared
      with tumor's good outcome. Integrity or breached of BM was visualized using
      immunohistochemistry technique with anti-type IV collagen antibody. The pattern
      of BM was classified as intact, breached, or absent in 24 BCCs and 11 SCCs with
      skull base invasion. Control group (good outcome) included 23 BCCs and 10 SCCs.
      Breached BM and absence of BM were respectively noted in 33.33% and 45.83% of
      BCCs with skull base invasion, compared with 8.33% and 17.395% in the control
      group ( P < .001). Regarding SCCs, ruptured and absent BMs were, respectively,
      noted in 36.36% and 63.64% of BCCs with skull base invasion, compared with 30%
      and 30% in the control group ( P = .075). In this study, destruction of BM was
      significantly more common in BCCs with skull base invasion, in comparison with
      those with good outcome. In SCC, this difference was not statistically
      significant.

PMID- 15944954
TI  - Carcinoma cuniculatum of the esophagus.
AB  - AIMS: Extremely well-differentiated squamous cell carcinoma with the features of
      so-called carcinoma cuniculatum (CC) is a rare neoplasm. We describe the
      clinicopathologic findings of the first 2 cases of CC of the esophagus. METHODS
      AND RESULTS: Two elderly men presented with symptoms and clinical signs of
      esophageal malignancy. Repeated endoscopic biopsies of their esophageal tumors
      were inconclusive. Resection revealed CC of the esophagogastric junction in both
      cases. The tumors extended into the adventitia but no lymph node metastases were
      present. In situ hybridization for human papillomavirus HPV subtypes was
      negative. CONCLUSION: Carcinoma cuniculatum is reported for the first time in the
      esophagus. The diagnosis of this tumor variant is difficult by means of
      cytological examination or by endoscopic biopsies alone. Carcinoma cuniculatum in
      this location shows biologic features similar to verrucous carcinoma (deep
      penetration, no lymph nodes metastases, and location at one end of the
      esophagus). No evidence of human papillomavirus could be demonstrated.

PMID- 15944955
TI  - Epithelioid cellular chordoma of the sacrum: a potential diagnostic problem.
AB  - We describe a sacral chordoma composed of solid nests of epithelioid cells. The
      tumor originated in the presacral area. Extensive clinical workup did not reveal
      any other lesion in the patient. In contrast to typical chordomas, this tumor
      contained only rare physaliferous cells, had no myxoid stroma, and was
      immunohistochemically unreactive with the antibody to S-100. The diagnosis of
      chordoma was supported by electron microscopy, which showed that the tumor cells
      contained numerous mitochondria surrounded by profiles of rough endoplasmic
      reticulum. The abundance of mitochondria, the narrow intercellular spaces,
      combined with a lack of glycogen, and a lack of extracellular myxoid material
      accounted for the epithelioid appearance of the tumor. We report this case to
      point out that the cellular chordomas can appear epithelioid in the sacrum and
      they may resemble metastatic squamous or transitional cell carcinomas.

PMID- 15944956
TI  - Duodenal gangliocytic paraganglioma: a radiological-pathological correlation.
AB  - Duodenal gangliocytic paraganglioma is a rare tumor that characteristically
      occurs in the second portion of the duodenum and typically presents with
      gastrointestinal bleeding. Gangliocytic paragangliomas have a characteristic
      triphasic microscopic appearance with epithelioid cells, spindle cells, and
      ganglion cells, resulting in a complex histology with features of paraganglioma,
      carcinoid, and ganglioneuroma. Duodenal gangliocytic paragangliomas have an
      excellent prognosis after surgical resection but metastatic spread to regional
      lymph nodes and recurrence may rarely occur. We report a case of duodenal
      gangliocytic paraganglioma and discuss the radiological and pathological
      differential diagnosis of this rare entity.

PMID- 15944957
TI  - Pulmonary lymphoma of the mucosa-associated lymphoid tissue type: Report of a
      case with cytological, histological, immunophenotypical correlation, and review
      of the literature.
AB  - A 59-year-old woman presented to The University of South Alabama, Mobile, Ala,
      with the complaint of shortness of breath. A chest radiograph showed bilateral
      nodules and interstitial infiltrates. The diagnosis of lymphoma was suggested on
      bronchial brush smears. Biopsy revealed a multifocal centrocyte-like lymphoid
      infiltrate involving the bronchial walls with lymphoepithelial lesions. The
      lymphocytes were positive for CD19, CD20, and CD22. A diagnosis of pulmonary
      lymphoma of the mucosa-associated lymphoid tissue type was established and the
      patient responded to chemotherapy treatment. Over the following 5 years, she
      suffered at least 2 recurrences involving the lung and breast for which she
      received additional treatment.

PMID- 15944958
TI  - Clear cell adenocarcinoma of the prostatic utricle in an adolescent.
AB  - We present a case of a 16-year-old boy with a primary clear cell adenocarcinoma
      of the prostatic utricle. The patient presented with a 6-month history of
      intermittent, nonpainful, gross hematuria and an associated right renal agenesis.
      Radiographic studies revealed the presence of a solid and cystic mass between the
      bladder neck and the cranium of the prostate. Serum tests, including prostate
      specific antigen, carcinoembryonic antigen, CA-19-9, and human chorionic
      gonadotropin, were performed and found to be within normal limits. A surgical
      resection of the mass including prostate and seminal vesicles was performed.
      Grossly, a polypoid exophytic tumor was present at the prostatic utricle.
      Histologically, the tumor shows the classical clear cell morphology reminiscent
      of the so-called mesonephric adenocarcinomas. At clinical follow-up, the patient
      is alive and well 18 months after surgical resection. The present case highlights
      an unusual phenomenon of the development of an unusual form of adenocarcinoma in
      an adolescent.

PMID- 15944959
TI  - Adenoid cystic carcinoma arising in a fibroadenoma.
AB  - Adenoid cystic carcinoma (ACC) of the breast is a rare neoplasm, accounting for
      only 0.1 % of all breast carcinomas. An intriguing factor of ACC in the breast is
      its good prognosis compared to ACC in other locations, mainly in the minor
      salivary glands. The incidence of axillary lymph node involvement is also very
      low compared to that of other breast tumors, and distant metastases are uncommon.
      We report the case of a 65-year-old woman with a 2-year history of a well
      circumscribed breast nodule sonographically thought to be a lymph node which was
      later excised because of rapid growth. Histologic examination showed an adenoid
      cystic carcinoma with squamous differentiation originating in a fibroadenoma. A
      review of the literature reveals no previous report of such a case.

PMID- 15944960
TI  - An endometrial stromal tumor with osteoclast-like giant cells.
AB  - Endometrial stromal tumors (ESTs) of the uterine corpus have a striking
      propensity to display diverse morphological variations, including sex cord-like,
      smooth muscle, or skeletal muscle differentiation; fibrous change; myxoid change;
      or bland endometrioid-type glands. They may also contain rhabdoid, foam, clear,
      or epithelioid/granular cells among others. Recently, we have encountered an EST
      showing smooth muscle differentiation and osteoclast-like giant cells that were
      predominantly concentrated in the areas showing smooth muscle differentiation.
      Osteoclastlike giant cells have not been previously reported in EST to our
      knowledge; thus, this finding expands the morphological spectrum of these tumors.
      In addition, although the level of infiltration at the peripheries of the tumor
      exceeded that allowable under the Tavassoli and Norris criteria for stromal
      nodules, it did not reach the classic permeative infiltration generally
      associated with endometrial stromal sarcomas. Historical, prognostic, and
      diagnostic aspects of margins in EST, especially in those borderline cases such
      as ours, are also discussed.

PMID- 15944961
TI  - Metastatic breast lobular carcinoma to tamoxifen-associated endometrial polyp:
      case report and literature review.
AB  - Tamoxifen is a widely used adjuvant treatment of breast carcinoma with partial
      estrogenic agonist effect. This activity may result in a spectrum of
      proliferative endometrial abnormalities including uterine polyps. We report a 53
      year-old woman receiving tamoxifen for previously excised breast lobular
      carcinoma who presented with vaginal bleeding. Histologic examination of the
      endometrium revealed typical morphology of tamoxifen-associated polyp with foci
      of metastatic lobular carcinoma. Metastatic breast carcinoma to tamoxifen
      associated polyp has rarely been described in the literature. Pathologists and
      gynecologists should be aware of this possibility in women who have a history of
      breast carcinoma and who are receiving tamoxifen. Careful histologic evaluation
      of the endometrium is crucial.

PMID- 15944962
TI  - Diaphragm disease: complete small bowel obstruction after long-term nonsteroidal
      anti-inflammatory drugs use.
AB  - Diaphragm-like stricture of the small bowel is an infrequent complication of the
      treatment of patients with nonsteroidal anti-inflammatory drugs (NSAIDs) and is
      part of the spectrum of diseases associated with NSAIDs injury. We report a
      patient with this condition who had used various forms of NSAIDs for over 20
      years. Patient presented with abdominal pain and indigestion. Plain abdominal
      film revealed small bowel obstruction. Surgical resection of jejunum and proximal
      part of ileum identified dilated thickened hyperemic mucosa alternating with
      areas of small bowel fibrotic constriction. The mucosal surface showed multiple
      pink-tan mucosal folds (circumferential ridges) with focal hemorrhage and edema.
      Our findings support the local stimulation and damage and reparative process seen
      with NSAIDs use. A high degree of suspicion and awareness of diaphragm disease is
      necessary in those patients.

PMID- 15944963
TI  - Endometrial hyperplasia/adenocarcinoma. a conventional approach.
AB  - Hyperplasia of the endometrium is a process characterized by an irregular,
      noninvasive proliferation of glands with a variable amount of stroma. Precise
      classification of endometrial hyperplasia in biopsy material is important in
      order to identify those hyperplasias that are likely to be precursors of
      endometrial adenocarcinoma. The current World Health Organization (WHO)
      classification provides a scheme that has become widely accepted, primarily
      dividing hyperplasias in to those with and those without cytologic atypia while
      the degree of glandular crowding (simple vs. complex) has secondary importance. A
      wide variety of other endometrial changes, ranging from artifacts, metaplasias
      and polyps to well-differentiated adenocarcinoma must be considered in the
      differential diagnosis. Well-differentiated adenocarcinoma is diagnosed when one
      of 3 essential criteria is found in biopsy specimens: (1) a confluent gland
      pattern; (2) an extensive papillary pattern; or (3) a desmoplastic stromal
      response. Using the WHO classification allows segregation of endometrial
      hyperplasia into clinically meaningful categories. Strict morphologic criteria
      also enable separation of hyperplasia from well-differentiated adenocarcinoma.

PMID- 15944964
TI  - Translating science: from idea, to research, to clinical practice.

PMID- 15944965
TI  - Frequency of trigeminal nerve injuries following third molar removal.
AB  - PURPOSE: To estimate oral and maxillofacial surgery reporting of the frequency of
      temporary and permanent inferior alveolar and lingual nerve damage from lower
      third molar extraction and injury etiology, and to identify factors associated
      with injury rates. MATERIALS AND METHODS: A postal survey was sent to all members
      of the California Association of Oral and Maxillofacial Surgeons requesting
      information on known instances of inferior alveolar and lingual nerve damage that
      had occurred in their practices over a 12-month period and known instances of
      permanent damage over their entire careers. RESULTS: Replies were obtained from
      535 California Oral and Maxillofacial Surgeons (OMFS) representing 86% of all
      OMFS in California. Instances of injury to the inferior alveolar nerve in a 12
      month period were reported by 94.5% of OMFS; 53% reported instances of lingual
      nerve injury in a 12-month period. Instances of permanent nerve injury of the
      inferior alveolar nerve were reported by 78% of OMFS; 46% reported permanent
      lingual nerve injury occurring during their professional lifetime. The overall
      estimated self-reported rate of injury was 4 per 1,000 lower third molar
      extractions for the inferior alveolar nerve and 1 per 1,000 extractions for the
      lingual nerve for all cases (temporary and permanent). In most cases (80%) of
      inferior alveolar nerve injury the cause was known, but in a majority of cases of
      lingual nerve injury (57%) the injury etiology was unknown. Self-reported rates
      of permanent injury were 1 per 2,500 lower third molar extractions for the
      inferior alveolar nerve and 1 per 10,000 lower third molar extractions for the
      lingual nerve. Injury rates were associated with provider experience (ie,
      extractions per year) and years in practice. CONCLUSION: This survey included a
      high percentage of California OMFS. Injury to the inferior alveolar and lingual
      nerve was reported by most OMFS in California following lower third molar
      removal, and many reported cases of permanent nerve injury, frequently with
      unknown cause.

PMID- 15944967
TI  - Vector control in transportation osteogenesis.
AB  - PURPOSE: To evaluate the ability to control vectors in the technique of
      transportation osteogenesis using 4 principles. PATIENTS AND METHODS: Sixteen
      defects measuring approximately 30-180 mm were retrospectively evaluated. Vector
      control was attempted using a single or combination of the following principles:
      multiple linear vectors, exaggerated linear distraction ("sausage effect"),
      braced guided distraction, and reorientation osteotomies. Observations were made
      regarding the ability to create the desired vectors. Angular deviation from
      desired vectors was determined and recorded numerically by evaluating either
      submental vertex or occlusal radiographs, stereolithographic models, or digital
      radiographs. Radiographic evaluation of symmetry alone was not used to determine
      the desired vector because a more laterally displaced segment was desirable to
      maintain favorable facial balance when soft tissue deficiency was pronounced. A
      subjective evaluation scale was developed to supplement the numerical values.
      RESULTS: Vector control primarily required the use of 2 or more principles. The
      most common combination was that of exaggerated linear distraction and
      reorientation osteotomy. CONCLUSION: The use of multiple linear vectors,
      exaggerated linear distraction ("sausage effect"), reorientation osteotomies, and
      braced guided distraction greatly assisted the operator in achieving the goal of
      symmetrical reconstruction. Transportation osteogenesis may be considered an
      effective tool in the box to reconstruct patients. In cases in which vector
      control is achieved, the advantages of diminishing the volume of bone graft
      required or achieving final bony reconstruction can outweigh the disadvantages of
      the technique.

PMID- 15944968
TI  - Ameloblastoma in Nigerian children and adolescents: a review of 79 cases.
AB  - PURPOSE: To descriptively review the clinicopathologic presentation and
      management of ameloblastoma in Nigerian children and adolescents and compare this
      with previous reports in the literature. METHODS AND MATERIALS: Data were
      collected from the case files of patients managed at 4 tertiary referral centers
      in Nigeria. RESULTS: Out of a total of 360 patients with a diagnosis of
      ameloblastoma, 79 were under 20 years of age at presentation (21.9%). Only 2.5%
      of the patients were under 10 years of age. The male-female ratio was 1.3 to 1
      with a peak age incidence of 15 years in males and 17 years in females. All the
      tumors were intraosseous and the majority (94.9%) were situated in the mandible.
      The most common morphologic type was solid multicystic ameloblastoma (82.3%). The
      majority (66.2%) had a multilocular radiographic presentation. In most patients
      (57.3%), the symphysial region of the mandible was involved by the tumor.
      However, exclusively anterior tumors constituted only 15.2% of the cases, while
      tumors involving anterior and posterior jaw regions constituted 41.1%. Resection
      was the predominant (72.2%) form of surgical management. CONCLUSION:
      Ameloblastoma in Nigerian children and adolescents exhibit some peculiar clinical
      features: these include the predominance of males, and of the solid multicystic
      morphologic type. In addition, there is site predilection for the symphysial
      region of the mandible. Radical surgical resection remains the predominant form
      of treatment. Therefore, varying degrees of interference with facial growth will
      be present in these children.

PMID- 15944969
TI  - Hemodynamics and oxygen saturation during intravenous sedation for office-based
      laser-assisted uvuloplasty.
AB  - PURPOSE: Patients undergoing office-based laser-assisted uvuloplasty (LAUP) for
      snoring or mild obstructive sleep apnea are generally obese and have a high
      Mallampati score. Because avoidance of supplemental oxygen during laser
      procedures is generally mandated, the potential for intraoperative desaturation
      is high. This study was designed to look at intraoperative hemodynamic changes,
      respiration patterns, and oxygen saturations during intravenous sedation with
      midazolam and fentanyl during LAUP procedures. MATERIALS AND METHODS: This was a
      retrospective anesthesia chart review of 15 consecutive patients undergoing
      midazolam/fentanyl intravenous sedation for office-based LAUP treatment for
      snoring and/or mild obstructive sleep apnea. Data recorded were noninvasive
      baseline and intraoperative hemodynamic measurements at 5-minute intervals for
      systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial
      pressure (MAP), pulse pressure (PP), pulse (P), and rate-pressure product (RPP).
      Data collected were reported as mean values with standard deviation. Statistical
      analysis using the Student's t test was performed and found significant for
      P<.05. RESULTS: All changes from baseline were statistically insignificant, SBP
      (P=.4), DBP (P=.2), MAP (P=.2), P (P=.1), PP (P=.9), RPP (P=.5), RR (P=.9), and
      SpO2 (P=.4), and all within +/-20% of baseline (range, -5.0% to +7.5%).
      CONCLUSION: Midazolam and fentanyl intravenous sedation with local anesthesia
      maintained intraoperative hemodynamic and oxygenation variables close to baseline
      for office-based LAUP procedures.

PMID- 15944970
TI  - Removal of miniplates in maxillofacial surgery: a follow-up study.
AB  - PURPOSE: We sought to follow-up a cohort of patients who had miniplates (plates)
      inserted in the oral and maxillofacial region during a 13-month period over 4
      years to study the incidence and factors associated with plate removal. PATIENTS
      AND METHODS: One hundred fifty-three patients had plates inserted in the oral and
      maxillofacial region in the Department of Oral & Maxillofacial Surgery,
      University Hospital Birmingham, UK, between November 1, 1998, and November 30,
      1999. All 153 patients' records were revisited on or after October 31, 2002,
      giving a minimum follow-up of 3 years and a maximum of 4 years. RESULTS: During a
      period of 13 months (November 1, 1998 through November 30, 1999), 308 plates were
      inserted into 153 patients. A total of 32 plates were removed from 21 patients by
      October 31, 2002, (10.4%) over 4 years; 27 plates were removed from 16 patients
      for purely plate-related symptoms, with infection being the most common cause
      accounting for 16 plates (50%) in 9 patients. Symptoms necessitating plate
      removal occurred within 52 weeks after insertion in 16 patients, accounting for
      23 of the plates removed (72%). The age of the patient at plate insertion may
      have some influence on plate removal but this was not significant. Seniority of
      the operator did not affect plate removal. CONCLUSION: Our experience with the
      removal of miniplates compares with previously published reports. Longitudinal
      follow-up at 4 years indicates that plate-related problems leading to removal are
      likely to occur in the first year after insertion.

PMID- 15944971
TI  - Analysis of inflammatory mediators in temporomandibular joint synovial fluid
      lavage samples of symptomatic patients and asymptomatic controls.
AB  - PURPOSE: It was our purpose to study IgA, IgG, and beta-glucuronidase levels in
      temporomandibular joint fluid lavage samples in order to find a correlation
      between biochemical markers and joint pathology. MATERIALS AND METHODS: Our
      patient population included 20 patients (18 female and 2 male) with severe pain
      and limitation of mandibular movement that failed to improve with at least 3
      months of a full course of nonsurgical therapy. After institutional review board
      approval, 13 control subjects (6 female and 7 male), with no history of
      temporomandibular joint pain/dysfunction, were obtained. Arthroscopic examination
      of the patient and control groups involved classification of joints for
      osteoarthritis and synovitis using a visual grading system. All synovial fluid
      samples were analyzed for beta-glucuronidase, IgA, and IgG using fluorometric
      assay and enzyme-linked immunosorbent assay. RESULTS: beta-Glucuronidase was
      significantly elevated (P<.05, t test) in the patient group compared with the
      control group (4.13+/-8.30 versus 0.9+/-0.83 [mean+/-SD]). The difference in the
      IgG level was also statistically significant (31,638+/-70,714 versus 4,407+/
      1,324) (P<.05, t test). IgA level showed a similar trend between the patient and
      control groups (6,315+/-19,037 versus 425+/-192) (P=.10, t test). CONCLUSIONS:
      Quantitative synovial fluid analysis of beta-glucuronidase, IgA, and IgG
      demonstrates elevated levels of inflammatory mediators in diseased joints
      compared with asymptomatic nondiseased joints. We hypothesize that high levels of
      IgA, IgG, and beta-glucuronidase in the TMJ synovial fluids are due to
      infiltration from the sera and chronic inflammatory cells residing in the
      synovium. High levels of immunoglobulins in a closed joint space can elicit
      strong inflammatory reaction and cause destruction to the joint tissues via
      complement activation and immune complex deposition. Complement activation
      increases blood vessel permeability to enable recruitment of neutrophilic
      leukocytes, which then liberate various lysosomal enzymes and damage the
      articular cartilage.

PMID- 15944972
TI  - Use of autologous platelet-rich plasma (PRP) in periodontal defect treatment
      after extraction of impacted mandibular third molars.
AB  - PURPOSE: The extraction of mesioangular impacted third molars may cause multiple
      periodontal defects at the distal root of the second molar. Platelet-rich plasma
      (PRP) is a material containing many autologous growth factors that may be used in
      repairing and preventing periodontal complications at the distal root of the
      second molar adjacent to the extracted third molar. PATIENTS AND METHODS: We
      analyzed the effects of autologous PRP on periodontal tissues after extraction of
      the third molar in 18 young patients (age, 21-26 years). Inclusion criteria were
      the presence of a pocket distal to the mandibular second molar with a probing
      depth>or=7.5 mm and a probing attachment level>or=6 mm. RESULTS: We observed, at
      12 weeks after surgery, a notable reduction in the probing depth and an
      improvement in the probing attachment level in those cases treated with PRP
      compared with the controls, as well as formation of new bone tissue in the bone
      defect. CONCLUSION: We showed that PRP is effective in inducing and accelerating
      bone regeneration for the treatment of periodontal defects at the distal root of
      the mandibular second molar after surgical extraction of a mesioangular, deeply
      impacted mandibular third molar.

PMID- 15944973
TI  - Computer-guided implant placement with immediate provisionalization: a case
      report.
AB  - Placement of dental implants in the esthetic zone is challenging for clinicians
      because of patients exacting esthetic demands and preexisting anatomy. This
      article presents an option for highly demanding surgical cases with the use of
      computer-guided implant placement and immediate provisionalization. This
      technique optimizes implant placement and soft tissue esthetics while providing
      the patient with an immediate fixed restoration.

PMID- 15944974
TI  - A comparison of synovial fluid pressure after immediate versus gradual mandibular
      advancement in the miniature pig.
AB  - PURPOSE: Mandibular advancement is a commonly performed surgical procedure for
      the treatment of mandibular hypoplasia. With the increased use of rigid fixation,
      there has been a decrease in the amount of relapse but an increase in the amount
      of force transmitted to the condyles. Gradual advancement of the mandible by
      distraction osteogenesis slowly overcomes the soft-tissue envelope and may
      decrease the amount of force exerted on the condyles. The purpose of this study
      was to develop an animal model to measure the magnitude of pressure associated
      with immediate versus gradual mandibular advancement. MATERIALS AND METHODS: A
      2.0-mm pressure transducer was placed in the superior joint space in 2 miniature
      pigs. In the first animal, immediate advancement of the mandible with rigid
      fixation was performed. The synovial fluid hydrostatic pressures were measured
      prior to surgery and postoperatively. A second animal underwent gradual
      advancement with distraction osteogenesis. The synovial fluid hydrostatic
      pressures were measured prior to and after each activation of the distraction
      device. The condyles were examined radiographically and microscopically. RESULTS:
      The superior joint space fluid pressures increased and remained elevated over a 5
      week period after immediate advancement. In the gradually advanced mandible, the
      pressures were elevated but returned to near baseline prior to the activation the
      following day. CONCLUSION: This animal model is useful to directly measure the
      pressure that is exerted on the condyle. This will allow further studies to
      compare methods for mandibular advancement. It is likely that gradual advancement
      of the mandible by distraction osteogenesis produces less force and causes less
      condylar resorption than large mandibular advancement stabilized with rigid
      fixation.

PMID- 15944975
TI  - Gene expression profile in oral squamous cell carcinoma: a pilot study.
AB  - PURPOSE: To study the gene expression profile of oral squamous cell carcinomas.
      MATERIALS AND METHODS: Gene expression profile was investigated in oral squamous
      cell carcinomas in 5 patients using the Atlas Glass Human 3.8 I Microarray (which
      detects cDNA obtained from cellular total RNA) (Clontech Laboratories, Palo Alto,
      CA). Data were normalized by the LOWESS method. Statistical significances of
      deviations from a 1:1 ratio were evaluated by t tests, with P<.05. RESULTS: Of
      the 3,757 genes analyzed, 322 (8.6%) were significantly overexpressed in tumoral
      tissue with respect to normal tissue, while 104 (2.8%) were significantly
      underexpressed. The affected genes fell into a wide range of functional
      categories. CONCLUSION: We consider that cDNA microarrays are of clear value for
      investigating the biology of these tumors, and that this technology may help in
      the molecular classification of oral squamous cell carcinomas and in the
      identification of targets for gene therapy.

PMID- 15944976
TI  - In vitro growth and differentiation of osteoblast-like cells on hydroxyapatite
      ceramic granule calcified from red algae.
AB  - PURPOSE: The purpose of this study was to analyze the interaction between
      osteoblast-like cells isolated from mandibular bone and hydroxyapatite ceramic
      bone substitute obtained from calcified red algae to assess the growth and
      differentiation of adherent cells on this biomaterial. MATERIALS AND METHODS: The
      macroporous ceramic material C GRAFT/Algipore (The Clinician's Preference LLC,
      Golden, CO) is composed of 100% hydroxyapatite and possesses specific mechanical
      and physiochemical properties. Osteoblast-like cells were seeded on 200 mg of
      biomaterial and cultured for 6 and 21 days under osteogenic differentiation
      conditions. Specific alkaline phosphatase activity, DNA, and protein content of
      the proliferating cells were analyzed. The morphology of the cells in contact
      with the biomaterial was examined by scanning electron microscopy. The
      osteoblastic phenotype of the cells was confirmed by analysis of the expression
      of bone-specific genes (osteocalcin, osteopontin and collagen type I) by semi
      quantitative reverse transcriptase polymerase chain reaction. RESULTS: The DNA
      and protein content increased over the culture period. Scanning electron
      microscopy showed cells spreading on the surface of the biomaterials, covering
      the macropores, and colonizing the depth of the particles. The analysis of the
      expression patterns of bone-related genes confirmed the osteoblastic phenotype of
      the cultured cells. CONCLUSION: The results of this study showed that
      hydroxyapatite ceramic bone substitute obtained from calcified red algae support
      the proliferation and differentiation of human osteoblast-like cells on its
      surface in vitro and might be suitable for use as scaffolds in tissue engineering
      strategies in vivo.

PMID- 15944977
TI  - Anatomical variations of the supraorbital, infraorbital, and mental foramina
      related to gender and side.
AB  - PURPOSE: The aim of the study was to examine the different anatomical variations
      of the supraorbital, infraorbital, and mental foramina related to gender and
      side. MATERIALS AND METHODS: Measurements were made on 110 adult skulls without
      mandibles and isolated mandibles. Gender was determined for each skull.
      Parameters measured bilaterally included the distances from the supraorbital and
      mental foramina to midline, from the infraorbital foramen to the anterior nasal
      spine, from the infraorbital foramen to the inferior orbital rim, and from the
      mental foramen to the inferior rim of the mandible and the angle between the line
      linking the infraorbital foramen with the anterior nasal spine and horizontal
      plane. Comparisons were made between genders and sides and statistical analysis
      was done where appropriate using Student's t test. RESULTS: There were 70 male
      and 40 female crania. Nature of the 3 foramina was similar between sides and
      genders. The average distance from the left supraorbital foramen to midline in
      females was significantly lower than that in males (2.42+/-0.04 versus 2.56+/
      0.05). The mean distances from the bilateral infraorbital foramina to anterior
      nasal spine in females were also significantly lower relative to those in males
      (3.28+/-0.03 versus 3.48+/-0.03 right and 3.31+/-0.03 versus 3.50+/-0.03 left).
      There were also considerable differences between sides in the average angle of
      the infraorbital foramen in both genders. CONCLUSIONS: Differences in several
      measurements suggest that gender and side should be considered when applying the
      anatomical variation data to an individual subject.

PMID- 15944978
TI  - Intraoral minor salivary gland neoplasms: review of 213 cases.
AB  - PURPOSE: Minor salivary gland tumors (MSGTs) constitute a heterogeneous group of
      neoplasms with great histomorphologic variation. This study reviews a large
      series of benign and malignant salivary gland tumors of the oral region and
      determines the incidence and the correlation of the histopathologic features with
      the clinical characteristics. MATERIALS AND METHODS: Two hundred thirteen cases
      of MSGT were retrospectively studied. Hematoxylin-eosin-stained slides were
      examined in all cases. Special stains and immunohistochemical stains were used in
      selected cases. Clinical characteristics of the neoplasms were also noted.
      RESULTS: One hundred nineteen tumors were benign (56%), and 94 tumors were
      malignant (44%). Pleomorphic adenoma was the most common benign tumor (93 of
      119). Canalicular adenoma was the second most common benign MSGT in our series
      (25 of 119). Of the 94 malignant MSGTs, mucoepidermoid carcinoma (MEC) (45 of
      94), adenoid cystic carcinoma (22 of 94), and polymorphous low-grade
      adenocarcinoma (18 of 94) were the most common. Most MECs (34 of 45) were low
      grade lesions. Of 5 central MECs, 3 cases occurred in the maxilla and 2 cases
      arose in the mandible. CONCLUSIONS: Benign intraoral MSGTs are slightly more
      common than malignant MSGTs. Pleomorphic adenoma is the most common MSGT, and MEC
      is the most common malignant variety. The palate is the most common site for
      minor gland neoplasms. Benign labial salivary gland neoplasms are more common in
      the upper lip, and malignant labial tumors are more common in the lower lip.

PMID- 15944979
TI  - A review of 318 odontogenic tumors in Kaduna, Nigeria.
AB  - PURPOSE: To analyze 318 odontogenic tumors seen at a tertiary oral care center in
      Kaduna, Nigeria for comparison with findings in previous Nigerian and world
      records. MATERIALS AND METHODS: A retrospective survey of odontogenic tumors
      based on the classification of Kramer et al was undertaken at the Maxillofacial
      Unit, Ahmadu Bello University Teaching Hospital, Kaduna, Nigeria, from all
      histopathologically proven cases of tumors and tumor-like lesions of the oral and
      perioral structures. Data were retrieved from case notes, radiographs,
      histopathology results, and follow-up records. Information collected were used to
      complete a questionnaire and subjected to analysis. RESULTS: There were 990 tumor
      and tumor-like lesions of the oral and perioral structures, of which 318 were
      odontogenic tumors (32%). Twelve histopathologic types of odontogenic tumors were
      found with more benign (n=314; 99%) than malignant (n=4; 1%). Ameloblastoma made
      up 233 (73%) of the tumors, followed by odontogenic myxoma (n=38; 12%),
      ameloblastic fibroma (n=9; 3%), and the adenomatoid odontogenic tumor (2%). Three
      cases of calcifying odontogenic cyst were co-existent with ameloblastoma (2) and
      ameloblastic fibro-odontoma (1). Among 275 surgically treated odontogenic tumors,
      enucleation was performed in 64 cases (23%), dentoalveolar segment resection with
      preservation of lower border of the mandible (n=33; 12%), segmental resection
      (n=168; 61%), and composite resection (n=9; 3%); 1 case was deemed inoperable. At
      least 8 cases of ameloblastoma (13%) recurred out of 60 followed up. CONCLUSION:
      Ameloblastoma is a fairly common tumor of Nigerian Africans accounting for 73% of
      odontogenic tumors and 24% of all tumors and tumor-like lesions of the oral and
      perioral structures. Various forms of resection are practiced to eradicate the
      tumor in view of the late presentation in our environment. Patients in Nigeria do
      not often return for follow-up reviews. A minimum of 5 years of follow-up reviews
      are necessary after treatment of ameloblastoma.

PMID- 15944980
TI  - Large swelling of the lateral neck.

PMID- 15944981
TI  - Failed root canals: the case for extraction and immediate implant placement.

PMID- 15944982
TI  - Failed root canals: the case for apicoectomy (periradicular surgery).

PMID- 15944983
TI  - Abstracts from the American Association Of Oral And Maxillofacial Surgeons annual
      scientific meeting: proportion published and time to publication.

PMID- 15944984
TI  - Osteomyelitis of the mandible due to Mycobacterium abscessus: a case report.

PMID- 15944985
TI  - Craniofacial invasive aspergillosis in an immunocompetent patient: a case report.

PMID- 15944986
TI  - Anesthetic management of a child with congenital insensitivity to pain with
      anhydrosis.

PMID- 15944987
TI  - Hybrid ameloblastoma and calcifying epithelial odontogenic tumor: case report.

PMID- 15944988
TI  - Necrotizing fasciitis of the cervical region in an AIDS patient: report of a
      case.

PMID- 15944989
TI  - Traumatic dislocation of the mandibular condyle into the middle cranial fossa
      treated with immediate reconstruction: a case report.

PMID- 15944990
TI  - Intraoral endoscopic enucleation of a central mandibular condylar lesion.

PMID- 15944991
TI  - Cat scratch disease: an unusual cause of facial palsy and partial ptosis: case
      report.

PMID- 15944992
TI  - Stereolithographic modeling technology applied to tumor resection.

PMID- 15944993
TI  - A new method to harvest ramus bone using the erbium, chromium:yttrium-scandium
      gallium-garnet laser.

PMID- 15944994
TI  - Interactive imaging for implant planning.

PMID- 15944995
TI  - The offshore medical degree: Views of a graduate.

PMID- 15944996
TI  - One-year angiotensin-converting enzyme inhibition plus mycophenolate mofetil
      immunosuppression in the course of early IgA nephropathy: a multicenter,
      randomised, controlled study.
AB  - Angiotensin converting-enzyme inhibition (ACEI) is a widely accepted treatment
      during established renal diseases and beneficial effects have also been reported
      in IgA nephropathy (IgAN). Immunosuppression with myco-phenolate mofetil (MMF)
      has recently been introduced in the treatment of immune-mediated renal diseases
      showing promising results. Preliminary clinical reports are also suggestive that
      MMF is effective in severe forms of IgAN. We propose a randomised prospective
      trial aimed to compare long-term renal survival of early IgAN in the course of
      ACEI therapy with or without MMF immunosuppression.

PMID- 15944997
TI  - How to limit screening of patients for atheromatous renal artery stenosis in two
      drug resistant hypertension?
AB  - BACKGROUND: The DRASTIC model based on nine variables (age, gender, recent onset
      of hypertension, smoking status, body mass index (BMI), abdominal bruit,
      atherosclerosis, dyslipidemia and creatininemia) has been proposed to predict
      renal artery stenosis (RAS) occurrence. METHODS: In a prospective multicenter
      study, the clinical usefulness of the DRASTIC model was checked in 336 patients
      with two-drug resistant hypertension. RAS was excluded using at least color
      Doppler sonography. RAS was diagnosed using at least renal angiography. The
      statistical dependence (Z(Rho)) analysis was applied to investigate further the
      relationships between each variable and presence of RAS. RESULTS: The prevalence
      of RAS (n=51) was 15%. The goodness-of-fit test that compared observed RAS to
      predicted RAS using the DRASTIC model was not significant. Accordingly, the
      multivariate logistic regression indicated that only three parameters (abdominal
      bruit, atherosclerotic vascular disease and BMI <25 kg/m2) were significantly
      linked to RAS. The Z(Rho) methodology revealed that calculated renal function <60
      ml/min and age >58 yrs (median) were also significantly linked to RAS. No
      variable or combination of variables offered satisfactory positive predictive
      values for the RAS diagnosis. The combination of the five significantly linked
      variables had a negative predictive value of 98%, and allowed RAS detection with
      a sensitivity of 96%. In our population, RAS screening could have been avoided in
      30% of our patients screened. CONCLUSIONS: The DRASTIC model was unsuitable for
      clinical use in our sample population. In our population, renal arteries were
      considered stenosis free with a probability of 98% in refractory hypertensive
      overweight patients, aged < or = 58 yrs, with satisfactory renal function and
      without both abdominal bruit and atherosclerotic vascular disease.

PMID- 15944998
TI  - The clinicopathologic basis of Graves' ophthalmopathy: a review.
AB  - PURPOSE: Graves' ophthalmopathy (GO) is a controversial disease, with
      disagreement within the medical community regarding its pathogenesis, diagnosis,
      and treatment. METHODS: We reviewed recent literature on clinical and
      pathological aspects of GO from both the endocrinologist's and ophthalmologist's
      perspective. RESULTS: Investigations into the pathogenesis of GO have included
      possible antigenic targets, orbital cell types, and development of animal models.
      Diagnosis has been improved recently with new tools and grading systems, but can
      be complicated by conditions that may simulate one or more of the findings of GO.
      The new findings of clinical studies also compel practitioners to reassess
      commonly used GO treatments such as orbital irradiation. CONCLUSIONS: Improved
      understanding of the pathogenic mechanisms of GO should hopefully lead to new
      diagnostic and therapeutic approaches to this problematic condition.

PMID- 15944999
TI  - Central corneal thickness in primary open angle glaucoma, pseudoexfoliative
      glaucoma, ocular hypertension, and normal population.
AB  - PURPOSE: This study was designed to determine the relationship between central
      corneal thickness (CCT) and intraocular pressure (IOP) measured by applanation
      tonometer in glaucomatous, ocular hypertensive, and normal eyes. METHODS: A total
      of 125 subjects were included in the study. Twenty-six had primary open angle
      glaucoma (POAG), 25 had pseudoexfoliative glaucoma (PXG), 24 had ocular
      hypertension (OHT), and 50 of them were normal. IOP values were measured by
      Goldmann applanation tonometer whereas CCT values were measured by ultrasonic
      pachymeter. RESULTS: CCT values in the OHT group (595.75+/-22.52 microm) were
      greater than the CCT values of the POAG group (539.92+/-21.50 microm), the PXG
      group (526.28+/-31.73 microm), and the normal group (533.96+/-29.25 microm)
      (p<0.05). Eight patients who were diagnosed with OHT showed IOP values of 21 mm
      Hg or lower with corrected IOP values according to CCT. CONCLUSIONS: Increased
      CCT may lead to falsely high values of IOP measured with Goldmann applanation
      tonometer. In this study, when IOP values of the OHT group were redefined
      according to the formulae regarding the CCT, the authors noted that one third of
      them were normal. Determination of the CCT in OHT cases is crucial since it has
      great impact on IOP values, measured with applanation tonometer, which is the
      main parameter in the diagnosis and follow-up of glaucoma.

PMID- 15945000
TI  - Cataract surgery combined with intravitreal injection of triamcinolone acetonide.
AB  - PURPOSE: To evaluate whether the addition of cataract surgery to an intravitreal
      injection of triamcinolone acetonide markedly increases frequency and spectrum of
      complications. METHODS: The comparative nonrandomized clinical interventional
      investigation included a study group of 60 eyes (56 patients) undergoing cataract
      surgery and additionally receiving an intravitreal injection of about 20 mg of
      triamcinolone acetonide and a triamcinolone control group of 290 eyes (262
      patients) that consecutively received an intravitreal injection of about 20 mg
      triamcinolone acetonide without cataract surgery. Reasons for intravitreal
      injection of triamcinolone acetonide were exudative age-related macular
      degeneration (n=228; 65%), diffuse diabetic macular edema (n=94; 27%), central
      retinal vein occlusion (n=17; 5%), and branch retinal vein occlusion (n=11; 3%).
      Mean follow-up was 8.6+/-6.8 months. A second control group included 1068
      patients (1068 eyes) who consecutively underwent routine cataract surgery without
      intravitreal injection. RESULTS: Study group and triamcinolone control group did
      not vary significantly in best visual acuity during follow-up (p=0.08), final
      visual acuity at the end of follow-up (p=0.30), maximal intraocular pressure
      during follow-up (p=0.99), frequency of an intraocular pressure higher than 21
      mmHg (p=0.66), and intraocular pressure at the end of follow-up (p=0.06).
      Postoperative infectious endophthalmitis, wound leakage or other corneal wound
      healing problems, persisting corneal endothelial decompensation, rhegmatogenous
      retinal detachment, marked postoperative pain, or a clinically significant
      decentration of the intraocular lens were not observed. Study group and the non
      triamcinolone control group did not vary significantly in the rate of posterior
      lens capsule rupture (p=0.11), postoperative infectious endophthalmitis, and
      persisting postoperative corneal endothelial decompensation. CONCLUSIONS: The
      addition of cataract surgery to an intravitreal injection of triamcinolone
      acetonide may not markedly increase amount and frequency of side effects and
      complications of intravitreal triamcinolone acetonide. No safe conclusions can be
      reached regarding differences in frequency of postoperative infectious
      endophthalmitis.

PMID- 15945001
TI  - Safety and efficacy of bimatoprost 0.03% versus timolol maleate 0.5%/dorzolamide
      2% fixed combination.
AB  - PURPOSE: To determine the efficacy and safety of bimatoprost given every evening
      versus the dorzolamide/timolol fixed combination (DTFC) given twice daily in open
      angle glaucoma and ocular hypertensive patients. METHODS: A double-masked, three
      center, prospective, randomized, crossover comparison with two 8-week treatment
      periods following a 4-week medicine free washout period. Diurnal curve
      intraocular pressures (IOPs) were taken at 08:00 (trough) and 10:00 and 16:00
      hours. RESULTS: A total of 35 patients were enrolled and 32 completed all
      evaluations. The diurnal untreated baseline intraocular pressures was 24.8 +/-
      2.4 mmHg. On the last day of treatment the mean diurnal intraocular pressures was
      17.4 +/- 2.9 for bimatoprost and 18.1 +/- 2.8 mmHg for DTFC (p = 0.35). The
      individual time points for intraocular pressures were not statistically different
      between groups. Both groups statistically reduced the intraocular pressures from
      baseline for each time point and for the diurnal curve (p < 0.05). Regarding
      ocular safety and tolerability, there was more conjunctival hyperemia with
      bimatoprost (n = 15) than with DTFC (n = 7, p = 0.013) and more burning and
      stinging with DTFC (n = 12) than with bimatoprost (n = 0, p = 0.0005). Few
      systemic adverse events were recorded and there was no statistical difference
      between groups for any individual event (p > 0.05). CONCLUSIONS: This study
      indicates that the intraocular pressures are lowered to a statistically similar
      amount with DTFC compared to bimatoprost in open-angle glaucoma and ocular
      hypertensive patients.

PMID- 15945002
TI  - Comparison between phaco-deep sclerectomy converted into phaco-trabeculectomy and
      uneventful phaco-deep sclerectomy.
AB  - PURPOSE: To evaluate and compare the results and complications of eyes that
      underwent a phaco-deep sclerectomy (DS) converted into phaco-trabeculectomy due
      to an intraoperative macroperforation with eyes undergoing uneventful phaco-DS.
      METHODS: The authors reviewed 106 eyes having a planned phaco-DS; 10 of them
      (9.4%) had to be converted into phaco-trabeculectomy because of a large
      perforation during the nonpenetrating procedure. Intraocular pressure (IOP),
      visual acuity, glaucoma medication evolution, and complications were evaluated
      and compared between groups. RESULTS: Eyes undergoing uneventful phaco-DS (n=96,
      Group 1) had a significantly higher postoperative IOP compared with those
      undergoing transformed phaco-trabeculectomy (n=10, Group 2) (p<0.05). One year
      postoperatively, 81.2% and 100% of the eyes in the Group 1 and 2, respectively,
      had an IOP pound 21 mmHg without treatment (p=0.206). One year postoperatively,
      eyes that underwent uneventful phaco-DS needed more glaucoma medications than
      eyes converted into phaco-trabeculectomy (p=0.014). Visual acuity improved more
      quickly in Group 1 (p<0.05). Hyphema and choroidal detachment rates were
      significantly higher in Group 2 (p=0.002 and p=0.027, respectively). CONCLUSIONS:
      Phaco-DS converted into phaco-trabeculectomy provides better midterm IOP control
      when compared with uneventful phaco-DS, but has more complications and worse
      visual acuity in the early postoperative period.

PMID- 15945003
TI  - Pilot study to evaluate the efficacy and safety of pneumatic trabeculoplasty in
      glaucoma and ocular hypertension.
AB  - PURPOSE: Following laser-assisted in situ keratomileusis (LASIK), intraocular
      pressure (IOP) is measurably lower in a significant number of cases. It has been
      proposed that the decrease in IOP may be a real event. Prior trials have
      evaluated pneumatic trabeculoplasty (PNT) in combination with concomitant
      glaucoma medications. The aim of this study was to determine the efficacy and the
      safety of PNT alone to lower IOP in patients with primary open angle glaucoma
      (POAG) or ocular hypertension (OH). METHODS AND RESULTS: A total of 37 subjects
      with POAG or OH were enrolled in a prospective, open-label, fellow-eye,
      multicenter trial to determine the IOP lowering effects of PNT. All subjects
      underwent ophthalmologic examinations and IOP measurements and were washed out
      from all glaucoma medications prior to the start of the study. The trial was
      intrapatient controlled for the first 30 days, with one eye receiving PNT at days
      0 and 7 and the fellow eye serving as the control. The second eye was treated
      with PNT at day 30. The patients were followed for 120 days, with the first eye
      receiving an additional PNT treatment at days 90 and 97. Two analyses-an intent
      to treat analysis in which the last IOP measurement for patients dropped from the
      study was carried forward and an analysis including only those patients who
      completed the trial-were performed. Of the 37 patients enrolled, 27 (73%)
      completed the study. For the intent to treat analysis the baseline mean IOP was
      24.7+/-1.9 mmHg for eye 1 and 23.6+/-2.3 mmHg for eye 2 and the difference was
      statistically significant (p<0.05). Using this analysis the differences between
      eye 1 mean IOP at days 1, 7, 14, and 60 and the baseline mean IOP were
      statistically significant (p<0.05). The differences between eye 2 mean IOP and
      the baseline mean IOP were statistically significant (p<0.05) at all time points
      except day 14 and day 30. The greater mean IOP reductions from the baseline mean
      IOP for eye 1 were at study day 1 (-16,1%), day 14 (-9%), and day 60 (-8.9%). For
      eye 2 they were at day 60 (-8.7%) and at day 120 (-9.1%). For the analysis that
      included only those subjects who completed the trial the decrease in eye 1 mean
      IOP from baseline was statistically significant (p<0.05) at all time points. The
      decrease in eye 2 mean IOP from baseline was statistically significant at all
      time points except day 30. Using this analysis the greater mean IOP reductions
      from the baseline mean IOP for eye 1 were at study day 1 (-19%), day 14 (-15.7%),
      day 37 (-16.3%), day 60 (-20.0%), day 90 (-18.1%), day 97 (-16.8%), and day 120 (
      15.8%). For eye 2 greater mean IOP reductions from baseline mean IOP were seen on
      day 37 (-13.0%), day 60 (-16.7%), day 90 (-15.5%), day 97 (-14.5%), and day 120 (
      7.2%). No statistically significant differences were found in mean IOP reduction
      between the two eyes treated. A total of 34 patients (92%) showed adverse
      effects: conjunctival hyperemia in 26 (70.3%) and conjunctival hemorrhage in 14
      (37.8%). CONCLUSIONS: This pilot study of PNT showed a potentially good IOP
      lowering effect on glaucoma and hypertensive patients. Additional studies would
      help to better define the types of patients who respond to PNT and to identify
      risk factors that may lead to treatment failure.

PMID- 15945004
TI  - Discrimination between normal and glaucomatous eyes with scanning laser
      polarimetry and optic disc topography: a preliminary report.
AB  - PURPOSE: To test the ability of structural parameters (as measured by scanning
      laser polarimetry (SLP) software 1.0.12 and confocal scanning laser
      ophthalmoscopy (CSLO) to discriminate between normal and glaucomatous eyes.
      METHODS: A total of 112 patients with primary open-angle glaucoma and 88 normal
      individuals were enrolled in the study. All individuals underwent a thorough
      ophthalmic evaluation, a 24-2 full threshold Humphrey visual field, SLP with the
      GDx, and CSLO with the TOPSS. Patients with marked cataract or low vision were
      excluded from the study. Cut-off points were selected and receiver operator
      characteristic (ROC) curves were created for each individual CSLO and SLP
      parameter. Finally, multivariate dicriminant formulas were developed in order to
      achieve a better sensitivity (Se)/specificity (Sp) ratio for the diagnosis of
      glaucoma, initially separately for each device, and then combining parameters
      from CSLO and SLP. RESULTS: The mean deviation for the glaucoma group was -10.63
      +/- 7.58 dB. Multivariate discriminant formulas resulted in better
      sensitivity/specificity ratios than any individual parameter, either for CSLO
      (Se: 90%; Sp: 81%; accuracy: 86%) or SLP (Se: 87%; Sp: 86%; accuracy: 86%). The
      multivariate formula combining parameters from both devices resulted in an
      improvement in the ability to diagnose glaucoma. An area under the ROC curve of
      0.97 was obtained, with a sensitivity of 93%, a specificity of 91%, and an
      accuracy of 92%. CONCLUSIONS: The combination of structural parameters derived
      from CSLO and SLP in a multivariate discriminant formula may enhance the ability
      to diagnose glaucoma. Further studies investigating a random population are
      needed in order to test the validity of this formula.

PMID- 15945005
TI  - Custom measurement of retinal nerve fiber layer thickness using STRATUS OCT in
      normal eyes.
AB  - PURPOSE: To evaluate variability of retinal nerve fiber layer (RNFL) thickness
      measurements in normal eyes and their correlation with optic disc diameter by
      using two different scan options of the ultimate commercial optical coherence
      tomography (OCT) unit (STRATUS OCT, Carl Zeiss Meditec, Inc., Dublin, CA).
      METHODS: In this observational case series and instrument validation study 30
      eyes of 30 normal subjects were enrolled. Each eye underwent optic disc vertical
      diameter measurement by means of both stereoscopic photography and planimetry and
      OCT; RNFL thickness measurements were performed using OCT. Three repetitions of
      two series of scans were performed. Each eye was scanned at two different options
      (RNFL thickness 3.4 and Nerve Head Circle). For each option descriptive
      statistics, analysis of variance, intraclass correlation coefficients (ICCs), and
      coefficients of variation (COVs) were calculated. To verify the correlation
      between the two methods of optic disc diameter assessment and to study the
      influence of optic disc diameter on RNFL measurement using the two different OCT
      options, Pearson's correlation coefficients were calculated. RESULTS: Optic disc
      diameter length ranged from 1.47 to 2.04 mm (mean 1.709 mm, SD +/- 0.147) with
      stereoscopic photographs, and from 1.47 to 2.02 mm (mean 1.703 mm, SD +/- 0.143)
      with OCT (Pearson correlation coefficient 0.999, p<0.001). Mean RNFL thickness
      was 89.29 mm (SD +/- 10.80 mm) using the RNFL thickness 3.4 scanning option and
      89.88 mm (SD +/- 1.72 mm) using the Nerve Head Circle protocol (Pearson
      correlation coefficient 0.065, p=0.734). The intersubject variance is higher
      using the RNFL thickness 3.4 option than using the NHC protocol (sum of square:
      1,014,760 vs. 25,741) (p<0.001); the intrasubject variance is very similar in the
      two groups (2,372 vs 2,360) (p=NS). The ICC is 99.89% when using the RNFL
      thickness 3.4 option, 95.62% with the NHC protocol (p=NS). COVs were 12.10% and
      1.91% by using RNFL thickness 3.4 and Nerve Head Circle option, respectively.
      Pearson's correlation coefficient was 0.988 (p<0.001) when comparing optic disc
      diameter and RNFL thickness by using the RNFL thickness 3.4 option and -0.016
      (p=0.932) when comparing optic disc diameter and RNFL thickness by using the
      Nerve Head Circle option. CONCLUSIONS: These results suggest that both scan
      options give good RNFL thickness measurement reproducibility; the use of the
      Nerve Head Circle option leads to less interindividual variability and can
      minimize the effect of differences in optic disc diameter on RNFL thickness
      measurements in normal subjects.

PMID- 15945006
TI  - Protective effects of antithrombin III on retinal ischemia/reperfusion injury in
      rats: a histopathologic study.
AB  - PURPOSE: To investigate the effect of antithrombin III (AT III) on retinal
      ischemia/reperfusion (I/R) injury in rats. METHODS: The study was carried out on
      10 Wistar albino rats (20 eyes) and four-vessel occlusion method was employed to
      induce retinal ischemia in this study. Rats were divided into two groups: Group I
      (control group, 10 eyes) and Group II (AT III, 10 eyes). In both groups,
      vertebral arteries were occluded bilaterally an electric needle coagulator under
      an operating microscope. A total of 48 hours after the initial procedure, the
      rats were re-anesthetized and both common carotid arteries were clamped to
      interrupt blood flow. In Group II, rats were injected intravenously with 250 U/kg
      of AT III 5 minutes before the induction of ischemia. Duration of ischemia was 30
      minutes. At the end of this period, clamp was removed for the reperfusion of the
      eye for 4 hours. Following the reperfusion period, the animals were killed by
      decapitation. Retinal sections were evaluated under light and electron
      microscope. The signs of I/R injury at the microscopic level, i.e., cellular
      degeneration, vacuolization between retinal layers, increase in the retinal
      thickness due to edema, mononuclear cell infiltration, and apoptotic cells, were
      recorded for each group. RESULTS: Retinal sections obtained from the rats in the
      AT III group revealed a well preserved retinal structure. When average thickness
      values of the two groups were compared to each other, the difference was
      significant with respect to inner nuclear and inner plexiform layers indicating
      increased retinal thickness values in Group I due to tissue edema resulting from
      I/R injury. Similarly, mononuclear cell infiltration and apoptotic cell counts
      were found to be significantly higher in control group compared to AT III group
      showing the inhibitory effect of AT III on leukocyte infiltration and apoptotic
      cell death in rat retina. CONCLUSIONS: Antithrombin III attenuated I/R injury in
      rat retina.

PMID- 15945007
TI  - Response time and safety profile of pulsed oral methotrexate therapy in
      idiopathic retinal periphlebitis.
AB  - PURPOSE: To evaluate the response time and safety profile of low-dose oral
      methotrexate pulsed therapy in idiopathic retinal periphlebitis (Eales' disease).
      METHODS: A tertiary care center-based prospective interventional study, based on
      visual acuity grading, was undertaken. Twenty-one consecutive patients with
      idiopathic retinal periphlebitis were administered 12.5 mg methotrexate as a
      single oral dose, once per week for 12 weeks (cumulative dose = 150 mg). Each
      patient was assessed for change in visual acuity grades. Time of first
      therapeutic response was also noted. Drug safety was monitored by laboratory
      tests that included twice-weekly white blood cells and differential counts, twice
      weekly platelet counts, and monthly liver function tests. RESULTS: Twenty-one
      eyes were assessed. Mean follow-up period was 6 months. All showed improvement in
      visual acuity grades. An excellent visual outcome (6/6 or better) was achieved in
      18 (69%) eyes. Time of first therapeutic response varied from 2 to 6 weeks with a
      majority of eyes (80%) showing response by 4 weeks (median = 3 weeks). All the
      side effects of methotrexate were mild or moderate in severity and rapidly
      reversible on dose reduction or discontinuation. No patient had any
      constitutional symptoms severe enough to necessitate cessation of therapy.
      CONCLUSIONS: Low dose oral methotrexate pulse therapy (at a dose of 12.5 mg/week)
      is clinically effective within 4 weeks, and is associated with an acceptable
      safety profile.

PMID- 15945008
TI  - Therapeutic effects of laser photocoagulation and/or vitrectomy in Eales'
      disease.
AB  - PURPOSE: To determine visual outcomes and regression of retinal
      neovascularization following laser photocoagulation and/or vitrectomy in eyes
      with Eales' disease. METHODS: In a retrospective noncomparative study, the
      authors reviewed the existing data of 67 eyes of 54 patients with a diagnosis of
      Eales' disease who had undergone laser photocoagulation and/or vitrectomy based
      on their clinical presentations. Main outcome measures were visual acuity changes
      and regression of retinal neovascularization of the eyes following treatment.
      RESULTS: Both laser therapy and vitrectomy improved visual acuity and induced
      regression of retinal neovascularization. Forty-three eyes had undergone laser
      therapy; their rate of visual acuity 320/30 improved from 53% before treatment to
      60% after treatment. Twenty-four eyes had undergone vitrectomy; rate of visual
      acuity 320/30 improved from 13% before surgery to 38% after surgery. In eyes that
      had undergone laser therapy, additional laser therapy controlled recurrent
      neovascularization in 47% of the eyes, but ultimately, 12% of them required
      vitrectomy. In the primary vitrectomized group, additional required treatment was
      repeat vitrectomy in 21%, and/or laser therapy in 29% of the eyes. CONCLUSIONS:
      Although laser photocoagulation should be the first line of treatment in Eales'
      disease, it cannot always induce regression of retinal neovascularization. In
      such cases vitrectomy may further enhance therapeutic success.

PMID- 15945009
TI  - Immunohistochemical study of extracellular matrix components in epiretinal
      membranes of vitreoproliferative retinopathy and proliferative diabetic
      retinopathy.
AB  - PURPOSE: The migration, proliferation, differentiation, and adhesion of cells and
      other cellular functions are influenced by the surrounding extracellular matrix
      in normal and wound healing conditions. The formation of epiretinal membranes, a
      wound healing process, is a serious complication of retinal diseases, the most
      important being proliferative diabetic retinopathy (PDR) and proliferative
      vitreoretinopathy (PVR). In the present study, the authors investigated the
      expression of various extracellular matrix components and in particular tenascin,
      fibronectin, laminin, collagen IV, and MMP-3 glycoprotein as well as the
      expression of glial fibrillary acidic protein in each type of epithelial membrane
      in order to elucidate the role of these molecules in the formation of these two
      types of membranes. METHODS: The authors performed immunohistochemistry in 14 PVR
      and 14 PDR membranes, using antibodies against the above mentioned extracellular
      matrix components. Tenascin and fibronectin were observed as major components in
      the extracellular matrix, while laminin and collagen type IV were detected as
      minor components in both types of membranes. A higher fibronectin expression in
      PVR compared with PDR membranes was found (p=0.0035). A positive relationship of
      its expression with the proliferative activity (p=0.15) and collagen type IV
      expression (p<0.0001) was also observed. RESULTS: Tenascin expression was
      positively correlated with glial fibrillary acidic protein positive cells in PDR
      membranes (p=0.04). Collagen type IV localized around vessels was observed with
      high levels in PDR membranes (p=0.0031). CONCLUSIONS: The results indicated that
      the extracellular matrix components seem to be involved in PVR and PDR,
      contributing to tissue remodeling and perhaps by different pathogenetic pathways,
      which could reflect different stages of development in these two types of
      membranes.

PMID- 15945010
TI  - Visual phenotype of multiple sclerosis in the Afro-Caribbean population and the
      influence of migration to metropolitan France.
AB  - PURPOSE: To describe the visual phenotype of multiple sclerosis (MS) in the Afro
      Caribbean population living in Martinique (French West Indies) and to specify the
      influence of the migration to metropolitan France on ocular impairment. DESIGN:
      Prospective consecutive observational case series. METHODS: A complete
      ophthalmologic examination was performed. PARTICIPANTS: A total of 112 patients
      of Afro-Caribbean origin with MS satisfying McDonald's diagnostic criteria,
      divided into 53 cases (47.3%), the non-migrant patients (group NM), who had never
      left the Caribbean basin, and 59 cases (52.7%), the migrant patients (group M),
      who had lived in metropolitan France for at least 1 year before age 15. RESULTS:
      MS first manifested as an impairment of the optic nerve in 41 cases (36.6%): 25
      cases (47.1%) in group NM and 16 cases (27.1%) in group M. Visual function was
      recovered in 13/25 cases (52%) in group NM compared to 13/16 cases (81%) in group
      M. Two-thirds of patients presented with a clinical ocular impairment, which was
      bilateral in 58.5% of cases in group NM. Fourteen cases (12.5%) met the criteria
      of neuromyelitis optica, nine cases (17%) in group NM and five cases (8.5%) in
      group M. In group NM, when the initial visual attack did not regress, the visual
      Expanded Disability Status Scale (EDSS) score was 5+/-1.5 ; 75% of patients had
      monocular blindness and 50% binocular. CONCLUSIONS: In the non-migrants (group
      NM), MS manifested more frequently with an optical neuropathy, the ocular
      impairment was more severe, and corresponded to neuromyelitis optica in 17% of
      the cases; a visual presentation and the absence of complete recovery from the
      first attack represented a factor of poor prognosis. This series is the largest
      description of the visual phenotype of MS in patients of African origin. The
      results confirm the preferential impairment of the optic nerve in the black
      population in the course of the disease. The migration towards an area of high
      prevalence of MS influences the visual phenotype in terms of a lower incidence
      and less severe prognosis of ocular impairment.

PMID- 15945011
TI  - Evidence-based guidelines on the referral of visually impaired persons to low
      vision services.
AB  - PURPOSE: One to two percent of the population in the Western world is visually
      impaired or blind. For most of these people there is no curative therapy.
      Therefore, the Dutch Ophthalmic Society has taken the initiative to develop an
      evidence-based guideline for the referral of visually impaired persons to low
      vision services. METHODS: A systematic literature search was performed in the
      Embase (1991-2001) and Medline (1966-2003) databases. Literature was searched for
      definitions of visual impairment, for physician-patient communication, and for
      outcome of interventions for visually impaired persons. Results of the articles
      that were selected were summarized and rated according to the level of evidence.
      Other considerations such as the current organization of rehabilitation for
      visually impaired persons in the Netherlands were also taken into account.
      RESULTS: The World Health Organization criteria were slightly adapted in order to
      include all people who experience problems with reading and other daily life
      activities due to visual impairment. A large number of recommendations were
      devised. Among these is that the complete diagnosis should be communicated to the
      patient and that a second appointment should be offered in which the diagnosis
      and potential treatment options are discussed again. Another recommendation is
      that in general visually impaired adults eligible for referral should be referred
      for the provision of low vision aids and that patients with complex problems or
      extensive rehabilitative demand should be referred to a rehabilitation center.
      CONCLUSIONS: This article presents a summary of the first European evidence-based
      guideline for the referral of visually impaired persons.

PMID- 15945012
TI  - A case of palpebral dirofilariasis.
AB  - PURPOSE: Dirofilaria repens infection is the most frequent and widespread
      dirofilariasis in the world. In Italy subcutaneous dirofilariasis is present
      especially in Northern-Central areas. METHODS: A woman with a palpebral lump is
      presented. RESULTS: After subcutaneous and muscular decollement, the authors
      found and removed a parasite. The final diagnosis was subcutaneous parasitosis
      due to D. repens. CONCLUSIONS: Surgery was both diagnostic and therapeutic.

PMID- 15945013
TI  - Bilateral lens subluxation associated with atopic eczema.
AB  - PURPOSE: Ectopia lentis remains a therapeutic challenge for ophthalmologists. It
      classically presents with a preceding history of blunt or penetrating ocular
      trauma, or it may be associated with other ocular disorders such as congenital
      glaucoma and aniridia, or concomitant hereditary systemic diseases such as Marfan
      syndrome and homocystinuria. METHODS: Case report. RESULTS: The authors describe
      a previously unreported mechanism of ocular trauma associated with continuous eye
      rubbing, resulting in bilateral recurrent subluxation of both intraocular lens
      and crystalline lens. CONCLUSIONS: It is useful for the ophthalmologist to be
      aware of this uncommon cause of ectopia lentis, since early advice and
      appropriate medical or surgical intervention may prevent more severe, sight
      threatening complications.

PMID- 15945014
TI  - Long-term persistence of fascia lata patch graft in glaucoma drainage device
      surgery.
AB  - PURPOSE: Conjunctival erosion in glaucoma drainage device surgery can be
      prevented by the use of patch grafts to cover the extraocular portion of the
      tube. Several materials can be used, among them human preserved fascia lata.
      METHODS: The authors present a case of a failed Ahmed glaucoma valve due to
      encapsulation of the bleb, in which the fascia lata patch placed to cover the
      tube was removed 32 months later, during the implantation of a second glaucoma
      drainage device. RESULTS: Histopathologic examination of the fascia lata patch
      demonstrated its persistence, without degradation or cellular infiltration.
      CONCLUSIONS: Human preserved fascia lata is a suitable material for tube covering
      in glaucoma drainage device surgery, with long-term survival.

PMID- 15945015
TI  - Intravitreal triamcinolone in the treatment of serous pigment epithelial
      detachment and occult choroidal neovascularization secondary to age-related
      macular degeneration.
AB  - PURPOSE: To report two cases of occult choroidal neovascularization (CNV) and
      serous pigment epithelial detachment (PED) treated with intravitreal
      triamcinolone (IVT) injections. METHODS: Interventional case reports. RESULTS:
      Both patients showed an increase in visual acuity and a complete flattening of
      the PED at 10 months (Case 1) and 4 months (Case 2) after IVT injections. No
      complications or adverse effects are reported. CONCLUSIONS: Future studies should
      be designed to investigate if IVT can effectively influence the clinical and
      functional outcome of eyes with serous PED and occult CNV secondary to age
      related macular degeneration, for which at the moment no treatment has been shown
      to be effective.

PMID- 15945016
TI  - Paraneoplastic optic neuropathy in a patient with a non-small cell lung
      carcinoma: a case report.
AB  - PURPOSE: To report a case and describe the clinical approach to a patient with a
      non-small cell lung carcinoma and paraneoplastic optic neuropathy. METHODS: Case
      report. RESULTS: A 79-year-old woman with known non-small cell lung carcinoma was
      admitted with a swollen optic disc in the right eye. After detailed clinical,
      laboratory, and imaging studies, the authors diagnosed paraneoplastic optic
      neuropathy, excluding other possible diagnosis. CONCLUSIONS: Paraneoplastic optic
      neuropathy is a clinical challenge and should be considered as a possible
      diagnosis in every cancer patient with optic disc edema.

PMID- 15945017
TI  - Varix of the vortex vein ampulla: a small case series.
AB  - PURPOSE: To report three cases of varix of the vortex vein ampulla. METHODS:
      Observational small case series. During 2002, three patients were examined for
      suspected choroidal melanoma. In all cases, the lesions were located at the
      equator or the periphery. RESULTS: The lesions became more prominent when the
      eyes were positioned in the direction of the lesion, and disappeared when firm
      pressure by ultrasound probe was applied on the globe, while the eye was in
      primary position, or fundus was examined with a three-mirror Goldmann contact
      lens. These dynamic characteristics were also demonstrated by color Doppler
      imaging. CONCLUSIONS: Varix of the vortex vein ampulla is an extremely rare
      condition. This diagnosis should be considered when an elevated choroidal lesion
      disappears when the fundus is examined with contact lens.

PMID- 15945018
TI  - Electron ionization induced mass spectral study of new metameric N-(E)
      stilbenyloxyalkylpiperidines, N-(E)-stilbenyloxyalkyl-4-methylpiperidines and N
      (E)-stilbenyloxyalkylmorpholines.

PMID- 15945019
TI  - High turbulence liquid chromatography online extraction and tandem mass
      spectrometry for the simultaneous determination of suberoylanilide hydroxamic
      acid and its two metabolites in human serum.
AB  - A reliable and sensitive method incorporating high turbulence liquid
      chromatography (HTLC) online extraction with tandem mass spectrometry (MS/MS),
      for simultaneous determination of suberoylanilide hydroxamic acid (SAHA) and its
      two metabolites, SAHA-glucuronide (M1) and 4-anilino-4-oxobutanoic acid (M2), in
      human serum, has been developed to support clinical studies. The HTLC technology
      significantly reduces the time required for sample clean-up since sample
      extraction and analysis are performed online. Clinical samples, internal
      standards (IS) and buffer are transferred into 96-well plates using a robotic
      liquid handling system. A 20 microL aliquot of prepared sample is directly
      injected into the HTLC/LC-MS/MS system where the matrix is rapidly washed away to
      waste and the analytes are retained on the narrow-bore extraction column (0.5 x
      50 mm), using an aqueous mobile phase at 1.5 mL/min. Analytes are then eluted
      from the extraction column and transferred to the analytical column using a
      gradient mobile phase prior to detection by MS/MS. Interference with
      determination of SAHA from in-source dissociation of M1 is eliminated by the
      chromatographic separation. The resolution of SAHA and M1 did not change for more
      than 1500 serum sample injections by applying an acid wash (15% acetic acid) on
      the extraction column. The linear calibration ranges for SAHA, M1, and M2 are 2
      500, 5-2000, and 10-2000 ng/mL, respectively. Assay intraday validation was
      conducted using five calibration curves prepared in five lots of human control
      serum. The precision expressed as relative standard deviation (RSD) is less than
      6.8% and accuracy is 94.6-102.9% of nominal values for all three analytes. Assay
      specificity, freeze/thaw stability, storage stability, and matrix effects were
      also assessed.

PMID- 15945020
TI  - Can radical cations of the constituents of nucleic acids be formed in the gas
      phase using ternary transition metal complexes?
AB  - Electrospray ionization (ESI) tandem mass spectrometry (MS/MS) of ternary
      transition metal complexes of [M(L(3))(N)](2+) (where M = copper(II) or
      platinum(II); L(3) = diethylenetriamine (dien) or 2,2':6',2''-terpyridine (tpy);
      N = the nucleobases: adenine, guanine, thymine and cytosine; the nucleosides:
      2'deoxyadenosine, 2'deoxyguanosine, 2'deoxythymine, 2'deoxycytidine; the
      nucleotides: 2'deoxyadenosine 5'-monophosphate, 2'deoxyguanosine 5'
      monophosphate, 2'deoxythymine 5'-monophosphate, 2'deoxycytidine 5'-monophosphate)
      was examined as a means of forming radical cations of the constituents of nucleic
      acids in the gas phase. In general, sufficient quantities of the ternary
      complexes [M(L(3))(N)](2+) could be formed for MS/MS studies by subjecting
      methanolic solutions of mixtures of a metal salt [M(L(3))X(2)] (where M = Cu(II)
      or Pt(II); L(3) = dien or tpy; X = Cl or NO(3)) and N to ESI. The only exceptions
      were thymine and its derivatives, which failed to form sufficient abundances of
      [M(L(3))(N)](2+) ions when: (a) M = Pt(II) and L(3) = dien or tpy; (b) M = Cu(II)
      and L(3) = dien. In some instances higher oligomeric complexes were formed; e.g.,
      [Pt(tpy)(dG)(n)](2+) (n = 1-13). Each of the ternary complexes [M(L(3))(N)](2+)
      was mass-selected and then subjected to collision-induced dissociation (CID) in a
      quadrupole ion trap. The types of fragmentation reactions observed for these
      complexes depend on the nature of all three components (metal, auxiliary ligand
      and nucleic acid constituent) and can be classified into: (i) a redox reaction
      which results in the formation of the radical cation of the nucleic acid
      constituent, N(+.); (ii) loss of the nucleic acid constituent in its protonated
      form; and (iii) fragmentation of the nucleic acid constituent. Only the copper
      complexes yielded radical cations of the nucleic acid constituent, with
      [Cu(tpy)(N)](2+) being the preferred complex due to suppression, in this case, of
      the loss of the nucleobase in its protonated form. The yields of the radical
      cations of the nucleobases from the copper complexes follow the order of their
      ionization potentials (IPs): G (lowest IP) > A > C > T (highest IP). Sufficient
      yields of the radical cations of each of the nucleobases allowed their CID
      reactions (in MS(3) experiments) to be compared to their even-electron
      counterparts.

PMID- 15945021
TI  - Study of metal complexes of a tripodal hydroxypyridinone ligand by electrospray
      tandem mass spectrometry.
AB  - The tripodal ligand N,N,N-tris[(1,hydroxy-2-pyridinon-6-yl)amide]propylamine was
      synthesized. It is composed of an anchor (nitrogen atom), a functional group
      (hydroxamate), and also a spacer of variable length defined by the number of
      methylene groups linking the anchor and the functional group. The
      characterization of this ligand in the presence of several divalent metal cations
      (Fe(II), Mn(II), Co(II) and Cu(II)), performed by electrospray ionization mass
      spectrometry (ESI-MS and ESI-MS/MS), allowed elucidation of oxidation states and
      also of different fragmentation patterns. The importance of the spacer length was
      studied in the case of the iron binary complex by comparing this ligand with
      another with a shorter spacer. In this way the stabilizing conditions, in which
      hydrogen bonds are implicated, were clarified.

PMID- 15945022
TI  - The high-mass component (>m/z 10 000) of coal tar pitch by matrix-assisted laser
      desorption/ionisation mass spectrometry and size-exclusion chromatography.
AB  - The size-exclusion chromatography (SEC) of acetone-soluble, pyridine-soluble and
      pyridine-insoluble fractions of a coal tar pitch indicates a bimodal distribution
      in each fraction. The proportion of high-mass material excluded from the SEC
      column porosity increases with solvent polarity. The polymer calibration of SEC
      shows the mass range of the small molecules to be from approximately 100 u to
      approximately 6000 u, with the mass range of the large excluded molecules above
      200 000 u and up to several million u. In contrast, matrix-assisted laser
      desorption/ionisation mass spectrometry (MALDI-MS) shows a similar low-mass range
      of ion abundances (< m/z 6000), but with a smaller range of high-mass ion
      abundances, from approximately m/z 10 000 to 100 000. The large molecules may
      have three-dimensional structures to allow molecules of relatively low mass to
      behave as if they are of large size in SEC. Laser desorption mass spectrometry of
      the acetone- and pyridine-soluble fractions produced molecular ions of polycyclic
      aromatics that can be related to the known compositions from gas chromatography
      (GC) mass spectrometry. The experimental conditions used to generate the bimodal
      distribution by MALDI-MS involve reducing the ion signal intensities to avoid
      overload of the detector and enable detection of the high-mass ions, by reducing
      the high-mass detector voltage (i.e. sensitivity) and increasing the laser power.

PMID- 15945023
TI  - 13C-Isotope ratio mass spectrometry as a potential tool for the forensic analysis
      of white architectural paint: a preliminary study.
AB  - Paints have a dual role in society, to protect materials from environmental
      agents such as ultraviolet light, moisture and oxygen, and to make painted
      materials look more attractive. Variability in paint samples is often due to
      binder and pigment type within the sample. The most common resin used in
      decorative paints is drying oil alkyd resin, which incorporates soybean oil and
      vinyl acrylic based latexes. Traditional analytical methods used by forensic
      scientists may be able to say whether two paint samples are indistinguishable but
      cannot conclusively say that they both originate from the same source. To find
      out if isotopic composition can provide an added dimension of information, 28
      different white architectural paints were analysed for (13)C abundance using
      isotope ratio mass spectrometry. In addition, variations in application, drying
      time and thickness were also investigated to assess the discriminatory power of
      (13)C data from white paints with an unknown history. Preliminary results
      indicate that this method could aid screening of paint samples.

PMID- 15945024
TI  - The Au(n) cluster probe in secondary ion mass spectrometry: influence of the
      projectile size and energy on the desorption/ionization rate from biomolecular
      solids.
AB  - A Au-Si liquid metal ion source which produces Au(n) clusters over a large range
      of sizes was used to study the dependence of both the molecular ion desorption
      yield and the damage cross-section on the size (n = 1 to 400) and on the kinetic
      energy (E = 10 to 500 keV) of the clusters used to bombard bioorganic surfaces.
      Three pure peptides with molecular masses between 750 and 1200 Da were used
      without matrix. [M+H](+) and [M+cation](+) ion emission yields were enhanced by
      as much as three orders of magnitude when bombarding with Au(400) (4+) instead of
      monatomic Au(+), yet very little damage was induced in the samples. A 100-fold
      increase in the molecular ion yield was observed when the incident energy of
      Au(9) (+) was varied from 10 to 180 keV. Values of emission yields and damage
      cross-sections are presented as a function of cluster size and energy. The
      possibility to adjust both cluster size and energy, depending on the application,
      makes the analysis of biomolecules by secondary ion mass spectrometry an
      extremely powerful and flexible technique, particularly when combined with
      orthogonal time-of-flight mass spectrometry that then allows fast measurements
      using small primary ion beam currents.

PMID- 15945025
TI  - Negative-ion electrospray ionization mass spectrometry of N-benzyloxycarbonyl
      protected 1-substituted and cyclic taurines.
AB  - The negative-ion mass spectrometric behavior of N-benzyloxycarbonyl-protected 1
      substituted and cyclic taurines has been investigated under electrospray
      ionization conditions. Their fragmentation pathways are proposed and supported by
      collisionally activated dissociation product-ion spectrometry. The deprotonated
      substituted taurines preferentially eliminate a molecule of benzyl alcohol to
      yield isocyanato-sulfonate ions, which further generate alkene-2-sulfonate ions
      by loss of isocyanic acid. The isocyanato-sulfonate ions of 1-substituted
      taurines could further generate aziridine-2-sulfonate ion via ring rearrangements
      by loss of CO plus benzyne and carbene moieties, respectively, while the
      isocyanato-sulfonate ions of cyclic taurines could further give rise to
      cycloalkene anion radicals. An obvious substituent effect on the fragmentations
      of the title compounds was observed.

PMID- 15945026
TI  - Determination of glufosfamide in rat plasma by liquid chromatography/tandem mass
      spectrometry.
AB  - A sensitive and selective high-performance analytical method based on liquid
      chromatography with tandem mass spectrometric detection (LC/MS/MS) was developed
      for the quantification of glufosfamide in rat plasma. Zidovudine was employed as
      internal standard. Glufosfamide was determined after methanol-mediated plasma
      protein precipitation using LC/MS/MS with an electrospray ionization interface in
      negative ion mode. Two sets of standard curves were developed, from 0.005 to 1.0
      microg/mL and from 1.0 to 50.0 microg/mL. The assay was accurate (% deviations
      from nominal concentrations < 5%), precise and reproducible (intra- and inter-day
      coefficients of variation < 10%). Glufosfamide in rat plasma was stable over
      three freeze/thaw cycles, and at ambient temperatures, for at least 2 h. The
      validated method was successfully applied to the determination of glufosfamide
      plasma concentrations in rats for 24 h following an intravenous administration of
      25 mg/kg.

PMID- 15945027
TI  - Development and validation of a liquid chromatography/tandem mass spectrometry
      procedure for the quantification of adefovir in human plasma.
AB  - To investigate the pharmacokinetics of adefovir as an anti-hepatitis B virus
      drug, a sensitive and specific liquid chromatography/tandem mass spectrometry
      method was developed and validated. After a simple protein precipitation using
      methanol, the post-treatment samples were analyzed on a C(18) column interfaced
      with a triple-quadrupole tandem mass spectrometer using positive electrospray
      ionization. A structural analogue, PMPA, was used as the internal standard. The
      method was linear in the concentration range 0.25-100 ng/mL. The lower limit of
      quantification was 0.25 ng/mL. The intra- and inter-day relative standard
      deviation over the entire concentration range was 5.7% or less. The accuracy
      determined at three concentrations (0.75, 10 and 80 ng/mL for adefovir) was
      within +/-2.5% relative error. The method described here was successfully applied
      for the evaluation of pharmacokinetic profiles of adefovir after single oral
      administration doses of 5, 10 and 20 mg adefovir dipivoxil to ten healthy
      volunteers.

PMID- 15945028
TI  - A study of electrospray mass spectrometry of new 1,4-dihydropyridines endowed
      with long alkyl chains.

PMID- 15945029
TI  - Fragmentations of isomeric sulfated monosaccharides using electrospray ion trap
      mass spectrometry.
AB  - Electrospray ionization combined with ion trap mass spectrometry (ESI-ITMS) is a
      powerful tool for structural analysis of complex carbohydrates. Although its
      application to sulfated glycans has been limited so far, it should provide
      critical information, such as sulfate positions, on their structures. In this
      work, MS(n) spectra of nine monosulfated monosaccharides, consisting of five
      hexoses and four N-acetylhexosamines, were measured in negative ion mode to find
      basic fragmentation rules for sulfated sugars. Two pairs of positional isomers
      with respect to sulfation, i.e., Gal4S and Gal6S, and GalNAc4S and GalNAc6S,
      showed characteristic fragmentation patterns in MS(3), and could be discriminated
      from one another by the appearance of particular diagnostic fragment ions that
      characterize individual isomers. It was also demonstrated that, even if a mixture
      of these positional isomers was analyzed, the proportion of each species could be
      estimated through analysis of the abundance ratios of the diagnostic ions.
      However, 3-O-sulfated saccharides (Glc3S and GlcNAc3S) gave a single abundant
      diagnostic ion in MS(2) corresponding to the hydrogensulfate ion, [OSO(3)H](-),
      and this characteristic clearly differentiated them from their positional
      isomers. In contrast, 6-O-sulfated diastereomers consisting of two groups, Glc6S,
      Man6S, Gal6S, and GlcNAc6S, GalNAc6S, could not be discriminated by the types of
      fragment ions; however, the abundance ratios of particular fragment ions differed
      significantly between Glc(NAc)6S and Gal(NAc)6S. Since ESI-ITMS yielded large
      quantities of useful information on structures of monosulfated hexoses and N
      acetylhexosamines in an extremely simple and reproducible manner, establishment
      of a comprehensive strategy based on ESI-ITMS(n) appears to be a promising
      technique for structural elucidation of sulfated complex carbohydrates.

PMID- 15945030
TI  - Analysis of the composition of immunoconjugates using size-exclusion
      chromatography coupled to mass spectrometry.
AB  - Recombinant monoclonal antibody drug products play an increasingly important role
      in the treatment of various diseases. Antibodies are large, multi-chain proteins
      and antibody preparations often contain several molecular variants, which renders
      them heterogeneous. The heterogeneity is further increased in immunoconjugates
      prepared by covalently linking several drug molecules per antibody molecule. As
      part of the product characterization, the molecular weights of the antibodies or
      their drug conjugates need to be measured. Electrospray ionization mass
      spectrometry (ESI-MS) is well suited for the analysis of recombinant antibodies
      and immunoconjugates. Sample preparation is an important element of ESI-MS
      analysis, in particular samples need to be freed of interfering charged species,
      such as salts and buffer components. In this paper, Amicon centrifugal filters,
      reversed-phase high-performance liquid chromatography (HPLC), and size-exclusion
      HPLC were evaluated for sample desalting. Size-exclusion HPLC, using aqueous
      acetonitrile as the mobile phase, directly coupled to ESI-MS provided the best
      performance and was optimized for the study of immunoconjugates. The results
      showed that antibodies carrying covalently linked maytansinoid molecules
      generated charge envelope profiles that differ from those of the non-conjugated
      antibody. For the determination of the distribution of the various conjugate
      species in an immunoconjugate sample prepared by randomly linking in the average
      3.6 drug molecules per antibody molecule, the experimental conditions needed to
      be carefully selected to allow acquisition of the whole spectrum containing the
      charge envelopes of all species.

PMID- 15945031
TI  - Analysis of organochlorines in harbor seal (Phoca vitulina) tissue samples from
      Alaska using gas chromatography/ion trap mass spectrometry by an isotopic
      dilution technique.
AB  - A gas chromatography/ion trap mass spectrometry (GC/ITMS) method was developed
      for the determination of organochlorine pesticides (OCPs), polychlorinated
      biphenyls (PCBs) and polychlorinated naphthalenes (PCNs) in harbor seal (Phoca
      vitulina) tissues. Tissue samples were homogenized, lyophilized and fortified
      with (13)C-PCBs 28, 123, 169 and 170, and then extracted with an accelerated
      solvent extractor with a mixture of hexane and methylene chloride (1:1, v/v).
      After lipid removal using a 40% H(2)SO(4)-modified silica gel column, all
      organochlorines were collected in one fraction and further fractionated with an
      activated carbon/silica gel (1:20) column into a first fraction containing OCPs,
      non-coplanar PCBs and (13)C-PCBs 28, 123 and 170, and a second containing PCNs,
      coplanar PCBs and (13)C-PCB 169. Prior to GC/MS/MS analysis, (13)C-PCB 169 was
      added into the first fraction as an injection standard and (13)C-PCB 170 into the
      second fraction to calibrate the recoveries of the fortified internal standards.
      This method can effectively eliminate matrix interferences, and has high
      selectivity and sensitivity. Recoveries averaged 45-86% for OCPs with relative
      standard deviations (RSDs) of 2-14%, 52-137% for PCBs with RSDs of 3-29% and 36
      152% for PCNs with RSDs of 7-29% from lard and chicken heart samples, which were
      used as alternative matrices to harbor seal samples in recovery studies. The
      limits of detection for OCPs, PCBs and PCNs were 0.7-1.9, 1.5-8.9 and 0.5-10 pg/g
      dry weight, respectively. This method can be used to analyze OCPs, PCBs and PCNs
      in harbor seal blubber, liver and kidney samples.

PMID- 15945032
TI  - New conditions for matrix-assisted laser desorption/ionization mass spectrometry
      of native bacterial R-type lipopolysaccharides.
AB  - A new sample preparation method for matrix-assisted laser desorption/ionization
      (MALDI) analysis of native rough-type lipopolysaccharides (R-type LPSs) is
      presented. In our MALDI mass spectra, besides the [M--H](-) ions, abundant ions
      originating from the cleavage between the 3-deoxy-D-manno-oct-2-ulosonic acid
      (Kdo) unit and the lipid A moiety are always present, giving important pieces of
      information about the structure of the molecules analyzed. Remarkably, in most
      cases, the comparison of the MALDI mass spectra of the intact R-type LPS with the
      O-deacylated one allowed us to obtain the structure of the lipid A moiety.

PMID- 15945033
TI  - The use of proteotypic peptide libraries for protein identification.
AB  - This paper describes an algorithm to apply proteotypic peptide sequence libraries
      to protein identifications performed using tandem mass spectrometry (MS/MS).
      Proteotypic peptides are those peptides in a protein sequence that are most
      likely to be confidently observed by current MS-based proteomics methods.
      Libraries of proteotypic peptide sequences were compiled from the Global Proteome
      Machine Database for Homo sapiens and Saccharomyces cerevisiae model species
      proteomes. These libraries were used to scan through collections of tandem mass
      spectra to discover which proteins were represented by the data sets, followed by
      detailed analysis of the spectra with the full protein sequences corresponding to
      the discovered proteotypic peptides. This algorithm (Proteotypic Peptide
      Profiling, or P3) resulted in sequence-to-spectrum matches comparable to those
      obtained by conventional protein identification algorithms using only full
      protein sequences, with a 20-fold reduction in the time required to perform the
      identification calculations. The proteotypic peptide libraries, the open source
      code for the implementation of the search algorithm and a website for using the
      software have been made freely available. Approximately 4% of the residues in the
      H. sapiens proteome were required in the proteotypic peptide library to
      successfully identify proteins.

PMID- 15945034
TI  - Mono- and diiodocyclophosphamide as possible internal standards for
      cyclophosphamide quantification: characterization by ion trap multi-stage mass
      spectrometry and effects of iodine-chlorine substitution on the fragmentation
      pattern.
AB  - Hospital personnel involved in antineoplastic drug preparation and administration
      to patients are exposed to large amounts of these drugs. Labour legislation
      indicates the necessity of planning monitoring strategies aimed at prevention
      and/or reduction of drug exposure. Monitoring strategies consist of quantitative
      determinations of indicators, present in environmental and biological matrices.
      Among the antineoplastic drugs widely used, cyclophosphamide (CP) has been
      identified as a suitable indicator of potential exposure to mixtures of
      antineoplastic drugs. Many literature methods for quantitative analysis of CP
      involve either liquid (LC) or gas chromatography (GC) with mass spectrometry
      (MS), both of which require use of a suitable internal standard. The present work
      focuses on the synthesis of mono- and diiodocyclophosphamide (CPI and CPI(2)) to
      be used as internal standard. These compounds were analyzed by GC/EI-MS/MS and
      LC/ESI-MS(n) using ion trap mass spectrometry. The product ion mass spectra are
      interpreted in terms of proposed structures of fragment ions. Iodine-chlorine
      substitution resulted in a weakening of the carbon-halogen bond with a noteworthy
      influence on the ion fragmentation processes. The proposed suitability of CPI and
      CPI(2) as internal standards was based on similarities to CP as regards
      ionization and fragmentation processes. The results obtained suggest that CPI
      could be used as internal standard for CP quantification by LC/ESI-MS/MS, and
      CPI(2) for GC/EI-MS/MS analyses.

PMID- 15945035
TI  - Characterisation via electrospray ionisation multistage mass spectrometry of
      three related series of nitrido technetium complexes containing phosphinothiolate
      and dithiocarbamate ligands.
AB  - Nine nitrido technetium compounds comprising bis-substituted Tc(N)(PS)(2) (1-4)
      (PS = bidentate phosphinothiolate ligands) and Tc(N)(dtc)(2) (5, 6) derivatives
      (dtc = bidentate dithiocarbamate), and mixed-ligand Tc(N)(PS)(dtc) (7-9) species,
      were subjected to electrospray ionisation mass spectrometry and MS(n)
      experiments. Bis-substituted phosphinothiolato complexes 1-4 lead to the
      straightforward formation of dinuclear species reasonably originating from proton
      bound dimers. These dinuclear species do not show, under collisionally induced
      fragmentation processes, the formation of monomeric units but cleavages related
      to the ligand framework, thereby proving the high stability of the [Tc--H(+)--Tc]
      bond. Bis-dithiocarbamate compounds 5 and 6 show, instead, abundant [M+H](+),
      [M+Na](+) and [2M+Na](+) ions, and their collisionally induced fragmentations are
      highly favoured with cleavages related to the C--N and C--S bonds. During these
      processes, the coordination of a water molecule to [MH-L](+) product ions is
      observed, as proved by the collisionally induced H(2)O loss detected for this
      species. Mixed-ligand compounds 7 and 8 show the protonated molecules and Na(+)
      cationised ions with fragmentation processes related to the dithiocarbamate
      moiety. This behaviour indicates that coordination of ether- and ester
      substituted dithiocarbamates to the [Tc [triple chemical bond] N] group is weaker
      than that of phosphinothiolates. Conversely, diethyldithiocarbamate inserted in
      mixed complex 9 enhances both C--N and Tc--S bonds, and fragmentation processes
      suggest that metal-phosphinothiolate and metal-dithiocarbamate show comparable
      strength.

PMID- 15945036
TI  - Analysis of bufadienolides in the Chinese drug ChanSu by high-performance liquid
      chromatography with atmospheric pressure chemical ionization tandem mass
      spectrometry.
AB  - The qualitative analysis of bufadienolides in the Chinese drug ChanSu was
      performed using high-performance liquid chromatography with atmospheric pressure
      chemical ionization tandem mass spectrometry (APCI-MS/MS). Bufadienolides are the
      major bioactive constituents of ChanSu, which is used to treat heart failure and
      cancer in traditional Chinese medicine. The APCI-MS fragmentation behavior of
      bufadienolides was studied. For bufadienolides with only hydroxyl substituents,
      the fragmentation was characterized by successive eliminations of H(2)O and CO
      molecules, and the profile of MS/MS product ions was correlated with the number
      of hydroxyl groups. If a C-16 acetoxyl group was present, the fragmentation of
      [M+H](+) ions was triggered by initial loss of 60 Da (HOAc). The elimination of
      CO was significant for bufadienolides with a 19-formyl group, and the 19-hydroxyl
      group could be characterized by the loss of 30 Da (HCHO). These fragmentation
      rules were applied to the identification of bufadienolides in a methanolic
      extract of ChanSu, which was separated on a C(18) column with gradient elution. A
      total of 35 bufadienolides were identified, including four new constituents. The
      method established here facilitated the convenient and rapid quality control of
      ChanSu crude drug and its pharmaceutical preparations.

PMID- 15945037
TI  - Auctions vs negotiations: a study of price differentials.
AB  - Recent contributions in auction and bargaining theory suggest that a procurer
      should place more faith in the power of competition among alternative suppliers
      than in his or her own negotiating skill. Based on data from 216 contracts
      between procurers and suppliers of medical and surgical articles, we test whether
      auctions and bargaining result in significantly different prices. The main
      results are that auctions give 'thicker' markets compared with negotiations, as
      expected, but that auctions do not result in significantly lower prices compared
      with negotiations.

PMID- 15945038
TI  - QALYs and capabilities: a comment on Cookson.

PMID- 15945040
TI  - Socioeconomic status, depression disparities, and financial strain: what lies
      behind the income-depression relationship?
AB  - Prior studies have consistently found the incidence and persistence of depression
      to be higher among persons with low incomes, but causal mechanisms for this
      relationship are not well understood. This study uses the National Longitudinal
      Survey of Youth 1979 cohort to test several hypotheses about the robustness of
      the depression-income relationship among adults. In regressions of depression
      symptoms on income and sociodemographic variables, income is significantly
      associated with depression. However, when controls for other economic variables
      are included, the effect of income is considerably reduced, and generally not
      significant. Employment status and the ratio of debts-to-assets are both highly
      significant for men and for women both above and below the median income. Fixed
      effects estimates suggest that employment status and financial strain are
      causally related to depression, but income is not. Instrumental variable
      estimates suggest that financial strain may not lead to depression.

PMID- 15945041
TI  - Pharmaceutical promotion and GP prescription behaviour.
AB  - The aim of this paper is to empirically analyse the responses by general
      practitioners to promotional activities for ethical drugs by pharmaceutical
      companies. Promotion can be beneficial as a means of providing information, but
      it can also be harmful in the sense that it lowers price sensitivity of doctors
      and it merely is a means of maintaining market share, even when cheaper,
      therapeutically equivalent drugs are available. A model is estimated that
      includes interactions of promotion expenditures and prices and that explicitly
      exploits the panel structure of the data, allowing for drug specific effects and
      dynamic adjustments, or habit persistence. The data used are aggregate monthly GP
      prescriptions per drug together with monthly outlays on drug promotion for the
      period 1994-1999 for 11 therapeutic markets, covering more than half of the total
      prescription drug market in the Netherlands. Identification of price effects is
      aided by the introduction of the Pharmaceutical Prices Act, which established
      that Dutch drugs prices became a weighted average of the prices in surrounding
      countries after June 1996. We conclude that GP drug price sensitivity is small,
      but adversely affected by promotion. Ltd.

PMID- 15945042
TI  - Think of a number... any number?
AB  - An examination of the willingness to pay values elicited from more than 3000
      persons involved in three independent studies revealed that the majority had
      offered one of a limited number of values from the ranges available to them.
      These values were 'prominent numbers', the use of which has been observed
      previously in circumstances where subjects feel that precise estimates of value
      are either difficult to make, or are not worth making. The existence of
      widespread prominence in response is suggestive of hypothetical bias in
      contingent valuation.

PMID- 15945043
TI  - Methods for incorporating covariate adjustment, subgroup analysis and between
      centre differences into cost-effectiveness evaluations.
AB  - BACKGROUND: Overall assessments of cost-effectiveness are now commonplace in
      informing medical policy decision making. It is often important, however, also to
      investigate how cost-effectiveness varies between patient subgroups. Yet such
      analyses are rarely undertaken, because appropriate methods have not been
      sufficiently developed. METHODS: We propose a coherent set of Bayesian methods to
      extend cost-effectiveness analyses to adjust for baseline covariates, to
      investigate differences between subgroups, and to allow for differences between
      centres in a multicentre study using a hierarchical model. These methods consider
      costs and effects jointly, and allow for the typically skewed distribution of
      cost data. The results are presented as inferences on the cost-effectiveness
      plane, and as cost-effectiveness acceptability curves. RESULTS: In applying these
      methods to a randomised trial of case management of psychotic patients, we show
      that overall cost-effectiveness can be affected by ignoring the skewness of cost
      data, but that it may be difficult to gain substantial precision by adjusting for
      baseline covariates. While analyses of overall cost-effectiveness can mask
      important subgroup differences, crude differences between centres may provide an
      unrealistic indication of the true differences between them. CONCLUSIONS: The
      methods developed allow a flexible choice for the distributions used for cost
      data, and have a wide range of applicability--to both randomised trials and
      observational studies. Experience needs to be gained in applying these methods in
      practice, and using their results in decision making.

PMID- 15945044
TI  - Interfacial Langmuir-Blodgett assembly of straight and parallel aligned
      nanoribbons.
AB  - The fabrication of one-dimensional nanomaterials is currently an important issue
      in nanoscience and nanotechnology. Herein, we report the construction of long,
      straight, and parallel aligned nanoribbons, by the in situ assembly of a novel,
      triangular amphiphilic molecule at an air-water interface. The 1,3,5-trimesyl-tri
      L-glutamic acid hexaester, which has an aromatic core with three hydrophilic arms
      bearing three amide units and ending with six ester groups, was spread on a water
      surface, forming a stable, ultrathin film with a plateau region in its isotherm.
      When the film was compressed to a surface pressures, which exceeded the plateau
      region, nanoribbons were formed. Atomic force microscopy, X-ray diffraction,
      Fourier-transform infrared spectroscopy, transmission electron microscopy,
      electron diffraction, and circular dichroism were used to characterize the film
      and the nanoribbons. The nanoribbons were formed due to the in situ
      transformation of a two-dimensional monolayer into a three-dimensional
      nanoarchitecture at the air-water interface. When the compound was spread onto
      the water surface, it first formed a monolayer. Compressing the film led to the
      overlap of the second layer on the monomolecular sublayer. This second layer
      formed nanoribbons in which the triangular molecules stood vertically (using two
      corners) on the sublayer. The nanoribbons were stabilized by the ordered packing
      of the triangular molecules, which were held together by intermolecular hydrogen
      bonding. The results present a facile procedure for constructing three
      dimensional, regular nanoarchitectures in a two-dimensional environment.

PMID- 15945046
TI  - Molecular dynamics and conformational kinetics of mono- and disaccharides in
      aqueous solution.
AB  - Acoustical attenuation spectra between 10 kHz and 2 GHz, complex dielectric
      spectra between 300 kHz and 40 GHz, and time-resolved non-equilibrium
      measurements are reported for aqueous solutions of various mono- and
      disaccharides with and without 2:1 valent salts. The spectra reveal a variety of
      relaxation regimes with relaxation times between 1 micros and 10 ps. In addition,
      the time-resolved observations enable the study of the mutarotation with
      relaxation times on the order of 10(3) s. Variation of the concentration and
      temperature as well as a careful choice of the saccharides allow a discussion of
      the relaxation processes in terms of a chair-chair ring inversion, two modes of
      pseudorotation, an exocyclic hydroxymethyl group rotation, a carbohydrate
      carbohydrate association, and, in the disaccharide solutions, a rotation of the
      rings relative to another. Salt-containing solutions show also relaxation
      phenomena reflecting different steps cation-carbohydrate association and
      variations in the carbohydrate conformational isomerizations and associations due
      to interactions with cations.

PMID- 15945047
TI  - Angle-resolved photoelectron spectroscopy of randomly oriented 3
      hydroxytetrahydrofuran enantiomers.
AB  - Circular dichroism in the angular distribution of valence photoelectrons emitted
      from randomly oriented 3-hydroxytetrahydrofuran enantiomers (ThS and ThR) has
      been observed in gas-phase experiments using circularly polarized vacuum
      ultraviolet (VUV) light. The measured dichroism for both ThS and ThR, acquired at
      the single magic angle theta=234.73 degrees and at photon energies of 22, 19, 16,
      and 14 eV, points to an asymmetric forward-backward scattering of the
      photoelectrons from their highest occupied molecular orbitals (HOMO) HOMO-1 and
      HOMO-2, of up to 5%, depending on the photon energy. The asymmetry reverses on
      exchange of either the helicity of the radiation or the configuration of Th. The
      photoionization dichroic D parameters of ThS and ThR have been measured and their
      values discussed in the light of LCAO B-spline density functional theory (DFT)
      predictions. While an acceptable agreement is found between the dichroic
      parameter measured and calculated at the highest photon energy for the HOMO and
      HOMO-2 orbitals of Th, a significant discrepancy is observed for the HOMO-1 state
      which is attributed to the floppiness of Th, in particular to the comparatively
      large sensitivity of the size and shape of its HOMO-1 on nuclear vibrational
      motion.

PMID- 15945048
TI  - How good is fluorine as a hydrogen-bond acceptor in fluorinated single-walled
      carbon nanotubes?
AB  - Ab initio (RI-MP2/TZVPP) computations were employed to investigate the
      interaction between hydrogen-bond donors H2O and CH3OH and covalently bound
      fluorine in organofluorine compounds. While the CFHO interaction energy is around
      3 kcal mol(-1) for unstrained systems, the linear correlation between
      pyramidalization angle at the carbon atom and the interaction energy suggests
      that increased binding can be obtained in strained systems. This is confirmed for
      the dihydrodifluoropyrene-methanol pair, but a large portion of the binding
      energy is due to the interaction of the pi system with the oxygen atom. Density
      functional periodic boundary condition computations (PBC-PBE/6-31G*) of the
      structures of (5,5) and (10,10) armchair (C2F)n fluorinated SWNTs (F-SWNTs)
      indicate that the pyramidalization at the fluorine-binding carbon atoms are too
      similar to that of CH3F to enhance the hydrogen-bond acceptor properties of
      fluorine significantly. The solubility of F-SWNTs in alcohols therefore could be
      due to a combination of hydrogen bonds and van der Waals interactions with the pi
      systems.

PMID- 15945051
TI  - Why I (really) became a therapist.
AB  - This article describes how the author really became a therapist and worked on his
      own social and performance anxiety. He was at first a follower of liberal
      psychoanalysis, but, in successfully using in vivo desensitization on himself, he
      overcame his anxiety and became highly constructivist. He finally created
      rational emotive behavior therapy, the pioneering cognitive-behavior therapy;
      integrated it with emotional-evocative and experiential methods; and used it to
      cope with much criticism he received about his active-directive techniques.

PMID- 15945052
TI  - Don't be a sheep: how this eldest daughter became a feminist therapist.
AB  - This article describes what I consider to be important influences on the
      development of my career as a psychotherapist. I explore familial effects, the
      influences of culture and of individual role models, and the impact of the
      women's movement on my career. I also examine the role that a contrarian,
      "outside" stance has played in the selection of my career and theoretical
      orientation.

PMID- 15945053
TI  - What inspired me to become a psychotherapist?
AB  - Six answers are given to the question of why I really became a psychotherapist.
      Of the six answers, three involve what may be considered inspirational
      influences: the inspirational benefits of what psychotherapy can offer,
      inspirational teachers, and inspirational practitioners.

PMID- 15945054
TI  - Growing up everyone's trusted confidante: why I really became a psychotherapist.
AB  - This article traces the roots and evolution of my pathway to becoming a
      psychotherapist and my still evolving professional interests and horizons. It
      discusses the journey taken, influences felt, and experiences encountered that
      have contributed to my expanding perspective and modus operandi. It travels from
      past to present, articulates my current thinking, and describes some of my major
      involvements in the early 21st century. The words "que sera, sera" (what will be,
      will be) are also prophetic of the future.

PMID- 15945055
TI  - Becoming a multicultural psychotherapist: the confluence of culture, ethnicity,
      and gender.
AB  - A Latina psychotherapist relates the influences of culture, ethnicity, gender,
      and class in her process of becoming a psychotherapist. Struggling with physical
      impediment, cultural translocation, racism, sexism, and their interaction, she
      has grounded her identity as a wounded healer. The pervasive role of history and
      sociopolitics in her life has contributed to her articulation of psychotherapy's
      role in liberation.

PMID- 15945056
TI  - Why I became a (brief) psychotherapist.
AB  - The author describes his development as a psychotherapist. He emphasizes both
      nurture and nature; he indicates that in addition to factors such as family and
      professional teachers and the zeitgeist, his choice was prefigured by the calling
      of character. He also discusses some of the influences that led to and confirmed
      his interest in approaches that fall under the general theoretical rubrics of
      brief and narrative constructive forms of therapy.

PMID- 15945057
TI  - Doing something.
AB  - The author relates her circuitous journey of becoming a psychotherapist,
      partially from the family ethic of helping others in need, but even more
      fundamentally from learning, on her grandfather's knee, to study character in the
      human face. She links those experiences to her love of studying and doing
      research with videotapes of therapy patients.

PMID- 15945058
TI  - Becoming and being a psychotherapist: a psychodynamic memoir and meditation.
AB  - The author reflects on the circumstances of his becoming a psychotherapist and
      meditates on their meaning. He notes the effect on his survival through childhood
      of his grandparents' emigration from Europe and the influence of his close-knit
      family on his personal needs and values. He then reflects on his early vocational
      interests; the transformational power of his education, as a student and faculty,
      at the University of Chicago; and the constructive force of his professional
      collaboration and personal friendship with Kenneth Howard. Finally, he considers
      why it is important to him not only to have become but to continue to be a
      psychotherapist.

PMID- 15945059
TI  - Developmental consequences of neuromuscular junctions with reduced presynaptic
      calcium channel function.
AB  - Evoked neurotransmitter release at the Drosophila neuromuscular junction (NMJ) is
      regulated by the amount of calcium influx at the presynaptic nerve terminal, as
      for most chemical synapses. Calcium entry occurs via voltage-gated calcium
      channels. The temperature-sensitive Drosophila mutant, cac(TS2), has a reduced
      amount of calcium entry during evoked stimulation. We have used this mutation to
      examine homeostatic regulatory mechanisms during development of the NMJ on muscle
      6 within the developing larva. The amplitude of the excitatory postsynaptic
      potentials are reduced for both the Ib and Is motor neurons in 3rd instar larvae
      which have been raised at 33 degrees C from the 1st instar stage. Larvae raised
      at 25 degrees C and larvae pulsed at 33 degrees C from the late 2nd instar for
      various lengths of time show a reduced synaptic efficacy as a 3rd instar. The
      results indicate that the nerve terminal cannot fully compensate physiologically
      in the regulation of synaptic transmission during larval life for a reduced
      amount of evoked calcium entry. Morphological comparisons of Ib and Is terminals
      in relation to length and numbers of varicosities are significantly reduced in
      cac(TS2), which also suggests a lack in homeostatic ability. These findings are
      relevant since many deficits in synaptic transmission in various systems are
      compensated for either physiologically or structural over development, but not in
      this case for reduced calcium entry during evoked transmission.

PMID- 15945060
TI  - Enhanced dopamine uptake in the striatum following repeated restraint stress.
AB  - In mice administered chronic stress--repeated overnight restraint stress for 7
      days--there was a prolonged enhancement of dopamine (DA) uptake into
      synaptosomes. The mRNA for the DA transporter (DAT) was found to be concomitantly
      increased in the midbrain, as was the binding of the transporter ligand mazindol
      to DAT in the nucleus accumbens and caudate-putamen. Kinetic analysis showed an
      increase in Vmax for DA, with little change in Km. No changes in tyrosine
      hydroxylase activity and tissue DA or 3,4-dihydroxyphenylacetic acid (DOPAC)
      content were observed. However, homovanillic acid (HVA) was found to be increased
      in the striatum of the stressed animals. Enhanced DAT activity attributable to
      chronic stress was still observed in animals treated with the DA D2 receptor
      antagonist haloperidol or the glucocorticoid receptor antagonist mifepristone.
      Modulation of DAT activity may be a physiological mechanism for regulating the
      concentration of DA that reaches receptors, following periods of stress.

PMID- 15945061
TI  - Methylphenidate analogs with behavioral differences interact differently with
      arginine residues on the dopamine transporter in rat striatum.
AB  - The methylphenidate analogs N-methyl-4-methyl-methylphenidate and N
      benzylmethylphenidate are believed to interact differently with the dopamine
      transporter (DAT) in vitro and in vivo. Herein, we report that methylphenidate
      and N-methyl-4-methyl-methylphenidate, but not N-benzylmethylphenidate, protect
      the rat striatal DAT from the arginine-selective chemical modifying agent,
      phenylglyoxal. This suggests that methylphenidate and N-methyl-4-methyl
      methylphenidate, but not N-benzylmethylphenidate, interact with the guanidine
      groups of arginine residues in the DAT of rat striatum. This differential
      interaction may, at least in part, explain the in vitro and in vivo differences
      between N-methyl-4-methyl-methylphenidate and N-benzylmethylphenidate.

PMID- 15945062
TI  - Picomolar concentrations of hibernation induction delta opioid peptide [D-Ala2,D
      Leu5]enkephalin increase the nerve growth factor in NG-108 cells.
AB  - The delta opioid peptide [D-Ala2,D-Leu5]enkephalin (DADLE) has been shown to be a
      neuroprotective agent via mechanisms that are not totally understood. We
      previously demonstrated that the i.p. injection of DADLE in mice causes an
      increase of nerve growth factor (NGF) in the brain. To further clarify the NGF
      increasing action of DADLE, we examined here the NGF-increasing effect of DADLE
      in vitro, using cultured NG-108 cells. DADLE dose-dependently increases the
      immunoreactive level of NGF in NG-108 cells in a bell-shape manner, with the
      effective DADLE concentrations in the picomolar range (0.01-100 pM). Also, DADLE
      at 1 pM selectively increases c-Jun and c-Fos, but not c-Rel. These results
      indicate that DADLE is one of the most potent agents in increasing the NGF in the
      biological system and that this action of DADLE involves selective increases of c
      Jun and c-Fos, transcription factors that promote the NGF expression.

PMID- 15945063
TI  - Metabotropic glutamate receptor protein expression in the prefrontal cortex and
      striatum in schizophrenia.
AB  - We investigated the expression of metabotropic glutamate receptors (mGluR) in the
      prefrontal cortex (PFC) and striatum in schizophrenia. mGluRs modulate the
      release and reuptake of synaptic glutamate and mediate some molecular correlates
      of neuroplasticity, including long-term potentiation. The mGluRs are expressed
      widely in the PFC and striatum, regions often implicated in the pathophysiology
      of schizophrenia. Thus, we hypothesized that abnormal expression of mGluRs might
      contribute to glutamatergic dysfunction observed in the PFC and striatum in
      schizophrenia. Accordingly, we measured the expression of metabotropic glutamate
      receptors (mGluRs) in Brodmann areas 9, 11, 32, and 46 in the prefrontal cortex
      (PFC) and the caudate, putamen, and nucleus accumbens in schizophrenia (16 cases,
      9 controls) by Western blot analysis. We found an increase in the expression of
      mGluR1a and mGluR2/3 immunoreactivity in the PFC in schizophrenia, while no
      changes in the expression of mGluR4a or mGluR5 were detected in this region. In
      the striatum we found no changes in the expression of any of the mGluRs studied.
      These results suggest that alterations of mGluR1a and mGluR2/3 expression in the
      PFC may contribute to the pathophysiology of schizophrenia, and support targeting
      these receptors for the generation of novel treatment modalities for this
      disabling illness.

PMID- 15945064
TI  - Learning and memory after neonatal exposure to 3,4-methylenedioxymethamphetamine
      (ecstasy) in rats: interaction with exposure in adulthood.
AB  - This study determined whether developmental and adult 3,4
      methylenedioxymethamphetamine (MDMA) exposures in rats have interactive effects
      on body temperature, learning, other behaviors, and monoamine concentrations in
      the hippocampus, prefrontal cortex, and striatum. Learning was assessed in the
      Cincinnati water maze (CWM), Morris water maze (MWM), and novel object
      recognition (NOR). On acquisition trials in the MWM, significant differences from
      developmental MDMA exposure were found on latency, cumulative distance, path
      length, and angle of first bearing to the goal, but the early and adult MDMA
      exposure group performed no worse than the developmental-only MDMA group. In the
      reversal trials, however, an interaction was seen: latency to the goal,
      cumulative distance, and angle of first bearing were increased in animals treated
      both developmentally and in adulthood with MDMA compared with those treated only
      developmentally. Other tests (elevated zero maze, CWM, NOR, and open-field
      activity) did not show an interaction, nor did hippocampal concentrations of
      serotonin or dopamine. However, several behavioral tests showed neonatal MDMA
      effects, including increased errors in the CWM, reduced time spent with a new
      object in the NOR test, and reduced locomotor activity in the open-field. By
      contrast, adult MDMA decreased the number of entries into open quadrants of the
      elevated zero maze. Litter effects were controlled by treating litter as the
      experimental unit and using mixed models repeated measures analyses.
      Correlational analyses suggested that the MWM reversal interaction involves
      multiple monoamine changes. The results indicate that developmental MDMA exposure
      can interact with adult exposure to interfere with some aspects of learning.

PMID- 15945066
TI  - Choosing psychotherapy as a career: why did we cross that road?
AB  - This article addresses the question "Why do people become psychotherapists?" via
      two approaches. The first involves an examination of the empirical and clinical
      literature on motivations and influences common to most psychotherapists. The
      second approach explores multiple pathways to becoming a psychotherapist by
      considering distinct gender-linked career trajectories. We identify 12 oft-noted
      themes in the literature on therapists' career paths (e.g., cultural
      marginalization, a psychologically minded way of understanding self and others)
      and link these to the narratives of the eight authors in this issue. Finally, we
      discuss ways in which understanding career motivations may be useful for
      therapists in their practice.

PMID- 15945065
TI  - Persistent upregulation of mu-opioid, but not adenosine, receptors in brains of
      long-term withdrawn escalating dose "binge" cocaine-treated rats.
AB  - There is evidence showing that the opioid and adenosine systems play an important
      role in cocaine addiction; fewer studies have examined their roles in cocaine
      withdrawal. To determine whether cocaine and/or chronic withdrawal from cocaine
      alters the specific components of the opioid and adenosine systems, we carried
      out quantitative autoradiographic mapping of mu-opioid, A1 and A2A adenosine
      receptors in the brains of rats treated with an escalating dose "binge" cocaine
      administration paradigm and of rats chronically withdrawn from cocaine. Male
      Fischer rats were injected with saline or cocaine (15 x 3 mg/kg/day for 4 days,
      20 x 3 mg/kg/day for 4 days, 25 x 3 mg/kg/day for 4 days and 30 x 3 mg/kg/day for
      2 days) at 1-h intervals for 14 days. Similarly treated rats were withdrawn from
      that paradigm for 14 days. A significant increase in [(3)H]DAMGO binding to mu
      receptors was detected in the frontal and cingulate cortex, as well as in the
      caudate putamen, of long-term withdrawn rats after an escalating dose "binge"
      cocaine administration paradigm and in chronic cocaine-treated rats. No
      significant cocaine-induced change was found in A1 or A2A receptor binding in any
      region analyzed. These results reconfirm that mu-opioid (MOP) receptors undergo
      upregulation in response to chronic escalating dose "binge" cocaine
      administration. This upregulation was shown for the first time to persist at
      least 14 days into withdrawal after escalating "binge" cocaine.

PMID- 15945067
TI  - Theoretical and experimental study of the adsorption of neutral glycine on silica
      from the gas phase.
AB  - The adsorption of neutral glycine onto amorphous silica was investigated both
      theoretically and experimentally. DFT calculations were performed at the BLYP
      631++G** level using a cluster approach. Several possible configurations
      involving the formation of H bonds between glycine and one, two, or three silanol
      groups (SiOH) were considered. The most favorable bonding of glycine with one
      silanol group (45 kJ mol(-1)) occurs through the COOH moiety, thus forming a
      cycle in which the CO group is an H-bond acceptor whereas the acidic OH group is
      an H-bond donor. With two or three silanol groups, additional H bonds are formed
      between the amine moiety and the silanol groups, which leads to an increased
      adsorption energy (70 and 80 kJ mol(-1) for two and three silanol groups,
      respectively). Calculated nu(CO), delta(HNH), and delta(HCH) values are sensitive
      to the adsorption mode. A bathochromic shift of nu(CO) as compared to the nu(CO)
      of free glycine (calculated in the 1755-1790 cm(-1) range) is found for glycine
      in interaction with silanol(s). The more H bonds are formed between the COOH
      moiety and silanol groups, the higher the bathochromic shift. For delta(HNH), no
      shift is found for glycine adsorbed on one and two silanol groups (where the
      amine is either not bound or an H-bond donor), whereas a bathochromic shift is
      calculated with three silanols when the amine moiety is an H-bond acceptor.
      Experimental FTIR spectra performed at room temperature for glycine adsorbed at
      160 degrees C on Aerosil amorphous silica exhibit bands at 1371, 1423, 1630, and
      1699 cm(-1). The experimental/calculated frequencies have their best
      correspondence for glycine adsorbed on two silanol groups. It is important to
      note that the forms giving the best correspondence to experimental frequencies
      are the most stable ones.

PMID- 15945068
TI  - Hypertonic upregulation of betaine transport in renal cells is blocked by a
      proteasome inhibitor.
AB  - The renal betaine transporter (BGT1) protects cells in the hypertonic medulla by
      mediating uptake and accumulation of the osmolyte betaine. Transcription plays an
      essential role in upregulating BGT1 transport in MDCK cells subjected to
      hypertonic stress. During hypertonic stress, the abundance of the transcription
      factor TonEBP increases and it shifts from the cytoplasm to the nucleus where it
      activates transcription of the BGT1 gene. Little is known about post
      transcriptional regulation of BGT1 protein. In the presence of the proteasome
      inhibitor MG-132, which blocked nuclear translocation of TonEBP, the hypertonic
      upregulation of BGT1 protein and transport was prevented and cell viability in
      hypertonic medium was impaired over 24 h. Urea also prevented the hypertonic
      upregulation of BGT1 protein and transport, but did not interfere with TonEBP
      translocation and cell viability. Shorter treatments of hypertonic cells with MG
      132 avoided viability problems and produced dose-dependent inhibition of
      translocation and transport. When stably transfected MDCK cells that over
      expressed BGT1 were treated for 6 h with hypertonic medium containing 3 microM MG
      132, there was 43% inhibition of nuclear translocation, 83% inhibition of BGT1
      transport, and no change in viability. While other proteasome functions may be
      involved, these data are consistent with a critical role for nuclear
      translocation of TonEBP in upregulation and membrane insertion of BGT1 protein.

PMID- 15945069
TI  - Choosing psychotherapy as a career: beyond "I want to help people".
AB  - This article briefly considers the career determinants of mental health
      professionals and then introduces the contents of the Journal of Clinical
      Psychology: In Session issue devoted to "why I became a psychotherapist."
      Psychotherapists are assuredly a special sort because the average person prefers
      to minimize the psychic sufferings of fellow humans and to avoid extensive
      contact with troubled individuals. Although the most frequent and conscious
      reason for becoming a psychotherapist is a desire to "help others," the decision
      is more complex and multidetermined than that. The multiple, intertwined motives
      are partly unconscious, impacted by chance encounters, and probably not well
      understood into late in one's career.

PMID- 15945070
TI  - CDG-IL: an infant with a novel mutation in the ALG9 gene and additional
      phenotypic features.
AB  - We describe the second case of congenital disorder of glycosylation type IL (CDG
      IL) caused by deficiency of the ALG9 a1,2 mannosyltransferase enzyme. The female
      infant's features included psychomotor retardation, seizures, hypotonia, diffuse
      brain atrophy with delayed myelination, failure to thrive, pericardial effusion,
      cystic renal disease, hepatosplenomegaly, esotropia, and inverted nipples.
      Lipodystrophy and dysmorphic facial features were absent. Magnetic resonance
      imaging of the brain showed volume loss in the cerebral hemispheres and
      cerebellum and delayed myelination. Laboratory investigations revealed low levels
      of multiple serum proteins including antithrombin III, factor XI, and
      cholesterol. Hypoglycosylation was confirmed by the typical CDG type 1 pattern of
      serum transferrin analyzed by isoelectric focusing. A defect in the ALG9 enzyme
      was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8
      in the patient's fibroblasts and confirmed by mutation analysis: the patient is
      homozygous for the ALG9 mutation p.Y286C. The causal effect of the mutation was
      shown by complementation assays in alg9 deficient yeast cells. The child
      described here further delineates the clinical spectrum of CDG-IL and confirms
      the significant clinical overlap amongst CDG subtypes.

PMID- 15945071
TI  - Physiological characterization of 45Ca2+ and 65Zn2+ transport by lobster
      hepatopancreatic endoplasmic reticulum.
AB  - The crustacean hepatopancreas is an epithelial-lined, multifunctional organ that,
      among other activities, regulates the flow of calcium into and out of the
      animal's body throughout the life cycle. Transepithelial calcium flow across this
      epithelial cell layer occurs by the combination of calcium channels and cation
      exchangers at the apical pole of the cell and by an ATP-dependent, calcium ATPase
      in conjunction with a calcium channel and an Na+/Ca2+ antiporter in the
      basolateral cell region. The roles of intracellular organelles such as
      mitochondria, lysosomes, and endoplasmic reticulum (ER) in transepithelial
      calcium transport or in transient calcium sequestration are unclear, but may be
      involved in transferring cytosolic calcium from one cell pole to the other. The
      ER membrane has a complement of ATP-dependent calcium ATPases (SERCA) and calcium
      channels that regulate the uptake and possible transfer of calcium through this
      organelle during periods of intense calcium fluxes across the epithelium as a
      whole. This investigation characterized the mechanisms of calcium transport by
      lobster hepatopancreatic ER vesicles and the effects of drugs and heavy metals on
      them. Kinetic constants for 45Ca2+ influx under control conditions were K(n)
      (m)=10.38+/-1.01 microM, J(max)=14.75+/-1.27 pmol/mg protein x sec, and n=2.53+/
      0.46. The Hill coefficient for 45Ca2+ influx under control conditions,
      approximating 2, suggests that approximately two calcium ions were transported
      for each transport cycle in the absence of ATP or the inhibitors. Addition of 1
      mM ATP to the incubation medium significantly (P<0.01) elevated the rate of
      45Ca2+ influx at all calcium activities used and retained the sigmoidal nature of
      the transport relationship. The kinetic constants for 45Ca2+ influx in the
      presence of 1 mM ATP were K(n) (m)=12.76+/-0.91 microM, J(max)=25.46+/-1.45
      pmol/mg protein x sec, and n=1.95+/-0.15. Kinetic analyses of ER 65Zn2+ influx
      resulted in a sigmoidal relationship between transport rate and zinc activity
      under control conditions (K(n) (m)=38.63+/-0.52 microM, J(max)=19.35+/-0.17
      pmol/mg protein x sec, n=1.81+/-0.03). The Addition of 1 mM ATP enhanced 65Zn2+
      influx at each zinc activity, but maintained the overall sigmoidal nature of the
      kinetic relationship. The kinetic constants for zinc influx in the presence of 1
      mM ATP were K(n) (m)=34.59+/-2.31 microM, J(max)=26.09+/-1.17 pmol/mg protein x
      sec, and n=1.96+/-0.17. Both sigmoidal and ATP-dependent calcium and zinc
      influxes by ER vesicles were reduced in the presence of thapsigargin and
      vanadate. This investigation found that lobster hepatopancreatic ER exhibited a
      thapsigargin- and vanadate-inhibited, SERCA-like, calcium ATPase. This
      transporter displayed cooperative calcium transport kinetics (Hill coefficient, n
      approximately 2.0) and was inhibited by the heavy metals zinc and copper,
      suggesting that the metals may reduce the binding and transport of calcium when
      they are present in the cytosol.

PMID- 15945072
TI  - Influence of stress on gonadotrophin induced testicular recrudescence in the
      lizard Mabuya Carinata.
AB  - Administration (ip) of FSH (10 IU/0.1 ml distilled water (dw)/lizard/alternate
      days/30 days) to adult male lizards, Mabuya carinata, during the early
      recrudescence phase of the reproductive cycle caused activation of spermatogenic
      and steroidogenic activity of the testis, as shown by a significant increase in
      mean number of spermatogonia, primary spermatocytes and spermatids, and serum
      levels of testosterone, as compared to initial controls. In addition, there were
      abundant spermatozoa in the lumen of the seminiferous tubules. Interestingly,
      administration of a similar dosage of FSH to lizards exposed to stressors
      (handling, chasing, and noise randomly applied, five times a day for 30 days)
      resulted in a significant increase in mean number of spermatogonia and primary
      spermatocytes over initial control values, whereas the number of secondary
      spermatocytes and spermatids and serum levels of testosterone did not
      significantly differ from those of initial controls, and were significantly lower
      than FSH treated normal lizards. Further, spermatozoa were infrequently found in
      the seminiferous tubules of these lizards. Treatment controls (receiving 0.1 ml
      dw/lizard/alternate days for 30 days) did not show significant variation in mean
      number of spermatogonia, spermatocytes and spermatids, and serum levels of
      testosterone from initial controls. Another group of lizards was exposed to
      stressors and did not receive FSH. These lizards showed a significant decrease in
      mean number of secondary spermatocytes compared to treatment controls and all
      other parameters did not significantly differ from those of both control groups.
      The results reveal that gonadotrophin-induced spermatogonial proliferation occurs
      under stressful conditions, whereas progress of spermatogenesis beyond primary
      spermatocyte stage is impaired due to inhibition (under stress) of gonadotrophin
      induced steroidogenic activity in M. carinata.

PMID- 15945073
TI  - Structure and permeability of the egg capsule of the bonnethead shark, Sphyrna
      tiburo.
AB  - In the viviparous bonnethead shark, Sphyrna tiburo, a fluid-filled, acellular egg
      capsule surrounds fertilized eggs and developing embryos throughout gestation.
      Like other placental shark species, the capsule remains intact even at the
      placental implantation site. Although its intervention between the uterine and
      embryonic tissues of the placenta has long been thought to mediate physiological
      exchange, little information is available concerning even its basic structure or
      permeability to solutes. The 1 mum thick capsule wall consists of an inner layer
      of gelatinous material and an outer layer consisting of at least three laminae of
      orthogonally arranged fibrous material. These fibers are irregular and often
      branched. Permeability experiments showed that solutes less than 1,355 Da diffuse
      across the egg capsule whereas those greater than 6,000 Da do not pass through
      the membrane. Solute movement across the capsule is a concentration-dependent
      phenomenon indicating diffusion rather than active transport. Experimental data
      also suggest that there is an increase in the permeability of the egg capsule to
      low molecular weight materials during mid- and late gestation. These observations
      are discussed in relation to the function of the egg capsule as a mediator of
      maternal-embryonic interactions in matrotrophic sharks.

PMID- 15945074
TI  - Changes of mRNA expression of vascular endothelial growth factor, angiopoietins
      and their receptors during the periovulatory period in eCG/hCG-treated immature
      female rats.
AB  - Angiogenic factors can induce the perifollicular capillary network in the theca
      interna that shows marked changes in and around the preovulatory luteinizing
      hormone (LH) surge. To get more information on their functional crosstalk, the
      aim of the present study was to investigate the manner of mRNA expression of
      vascular endothelial growth factors (VEGFs) 120, 164, angiopoietin (Ang)-1, Ang-2
      and their specific receptors during the periovulatory phase. We used an
      established equine and human chorionic gonadotropins (eCG/hCG)-derived
      experimental model capable of stimulating naturally occurring follicular
      maturation, ovulation and corpus luteum (CL) formation. On day 28 postpartum,
      immature female rats were administrated s.c. with 10 IU of eCG to promote
      follicular development, followed 48 hr later by i.p. administration of 20 IU of
      hCG. Ovaries were dissected at 0, 6, 12, 18 and 24 hr after hCG treatment, and
      were obtained on day 30 in the untreated control. After induction of follicular
      growth by the eCG treatment, each mRNA expression of VEGF 120, VEGF 164,
      Neuropilin-1 and Flt-1 significantly increased. The peaks in mRNA expressions of
      VEGF120 and VEGF164 were both found at 18 hr after hCG treatment. Flk-1 mRNA
      expression maintained up to 6 hr after hCG treatment, and then decreased at 12,
      18 and 24 hr after hCG treatment. Ang-2 mRNA expression increased in the ovaries
      at 6 and 12 hr after hCG treatment. Tie-2 mRNA expression decreased at 24 hr
      after the treatment of gonadotropins. Our findings suggest that ovarian vascular
      formation during the periovulatory period including preovulatory follicles,
      ovulation and CL formation may develop via crosstalk of the VEGF-Flt-1 and Ang
      Tie2 systems.

PMID- 15945075
TI  - Osmoregulatory physiology of pyloric ceca: regulated and adaptive changes in
      chinook salmon.
AB  - Functions of the anatomically obvious, yet peculiar, pyloric ceca of the fish gut
      have been a source of conjecture for over two millennia since Aristotle
      hypothesized on digestive utilities. Here, we demonstrate regulated and adaptive
      changes in osmoregulatory physiology of ceca from chinook salmon (Onchorhynchus
      tshawytscha). Transfer of salmon from freshwater to seawater (both short- and
      long-term) significantly stimulated both fluid uptake from 5.1 to 8.3-9.3
      microl/cm2/hr and also Na+/K+ -ATPase from 6.5 to 8.3-9.6 micromol/ADP/mg
      protein/hr. Similar changes were induced with implants of cortisol, which
      resulted in high physiological cortisol levels in plasma. Ceca, which can number
      about 200 in chinook salmon, were estimated to account for the majority of fluid
      uptake capacity of the intestine and, after long-term seawater adaptation, the
      proportion of uptake capacity was sixfold higher. Transport physiology of ceca is
      thus under environmental and endocrine control indicative of an important role in
      salt and water homeostasis.

PMID- 15945076
TI  - Seasonal changes in serum leptin of the feral raccoon (Procyon lotor) determined
      by canine-leptin-specific ELISA.
AB  - Several reports have been published on blood leptin concentrations in feral
      animals, including members of the Carnivora, using a commercially available multi
      species radioimmunoassay (RIA) kit with anti-human leptin antibody. However, we
      observed weak immunoreactivity between recombinant canine leptin and anti-human
      leptin antibody, suggesting a limitation in the applicability of the RIA kit for
      leptin assays in Carnivora species. We tested the applicability of RIA and
      sandwich enzyme-linked immunosorbent assay (ELISA) with anti-canine leptin
      antibody to assay blood leptin in the dog (Canis familiaris) and the raccoon
      (Procyon lotor). When RIA was used for recombinant canine leptin and dog sera,
      values were much lower than those determined by ELISA at higher concentrations
      (>10 ng/ml), while rather higher at lower concentrations (<2 ng/ml). A similar
      discrepancy between the two methods was found for serum leptin concentrations in
      raccoons. Clear seasonal variations were observed by ELISA, but not by RIA, with
      high values in autumn (3.46+/-0.45 ng/ml) and low values in spring and summer
      (0.71+/-0.07 ng/ml). Serum leptin concentrations in raccoons correlated
      positively with their body weight (r=0.753) and body mass index (r=0.755),
      corroborating our previous findings of a strong positive correlation between
      serum leptin concentrations and body fat content in dogs. Thus, the canine leptin
      ELISA is useful for assays of dog and raccoon leptin, and blood leptin is a good
      marker of nutritional condition in the species of Carnivora assayed in this
      study.

PMID- 15945077
TI  - Daily light regulates seasonal responses in the migratory male redheaded bunting
      (Emberiza bruniceps).
AB  - This study analyzed the role of day length in regulation of seasonal body
      fattening and testicular growth in a latitudinal Palaearctic-Indian migrant, the
      redheaded bunting (Emberiza bruniceps). When exposed to increasing photoperiods
      (hours of light: hours of darkness; 11.5L:12.5D, 12L:12D, 12.5L:11.5D, 13L:11D,
      14L:10D, and 18L:6D) for 9-12 weeks, buntings responded in a photoperiod
      dependent manner and underwent growth and regression cycle under photoperiods of
      > or =12 hr per day. Also, the response to a long photoperiod of birds that were
      held under natural photoperiods at 27 degrees N for 2 years was similar to those
      who arrived the same year from their breeding grounds ( approximately 40 degrees
      N), suggesting that the experience of higher amplitude day-night (light-dark, LD)
      cycles during migratory and breeding seasons were not critical for the subsequent
      response (initiation-termination-reinitiation) cycle. Another experiment examined
      entrainment of the circadian photoperiodic rhythm in buntings by subjecting them
      to T=24+/-2 hr LD-cycles with 8 hr photophase and to T=22 and 24 hr with 11 hr
      photophase. The results showed a reduction in critical day length under T=22 hr
      LD-cycle. In the last experiment, we constructed an action spectrum for
      photoperiodic induction by exposing birds for 4.5 weeks to 13L:11D of white
      (control), blue (450 nm), or red (640 nm) light at irradiances ranging from 0.028
      to 1.4 W m(-2). The threshold light irradiance for photoinduction was about 10
      fold higher for blue light, than for red and white lights. These results conclude
      that the daily light of the environment regulates the endogenous program that
      times seasonal responses in body fattening and testicular cycles of the redheaded
      bunting.

PMID- 15945078
TI  - Evidence for different pharmacological targets for imidazoline compounds
      inhibiting settlement of the barnacle Balanus improvisus.
AB  - We describe the effect of eight different imidazoline/guanidinium compounds on
      the settlement and metamorphosis of larvae of the barnacle Balanus improvisus.
      These agents were chosen on the basis of their similar pharmacological
      classification in vertebrates and their chemical similarity to medetomidine and
      clonidine, previously described as highly potent settlement inhibitors (nanomolar
      range). Seven of the tested compounds were found to inhibit settlement in a dose
      dependent manner in concentrations ranging from 100 nM to 10 microM without any
      significant lethal effects. In vertebrate systems these substances have
      overlapping functions and interact with both alpha-adrenoceptors as well as
      imidazoline binding sites. Antagonizing experiments using the highly specific
      alpha(2)-antagonist methoxy-idazoxan or agmatine (the putative endogenous ligand
      at imidazoline receptors) were performed to discriminate between putative
      pharmacological mechanisms involved in the inhibition of cyprid settlement.
      Agmatine was not able to reverse the effect of any of the tested compounds.
      However, methoxy-idazoxan almost completely abolished the settlement inhibition
      mediated by guanabenz (alpha(2)-agonist, I(2) ligand), moxonidine (alpha(2)
      agonist, I(1) ligand) and tetrahydrozoline (alpha-agonist, I(2) ligand). The
      actions of cirazoline (alpha(1)-agonist, I(2) ligand) BU 224 (I(2) ligand) and
      metrazoline (I(2) ligand) were not reversed by treatment with methoxy-idazoxan.
      These results suggest that the settlement inhibition evoked by the I(2) ligands
      and alpha(2)-agonists used in this study of the neurologically simple but well
      organized barnacle larva is mediated through different physiological targets
      important in the overall settlement process.

PMID- 15945079
TI  - Branchial osmoregulatory response to salinity in the gilthead sea bream, Sparus
      auratus.
AB  - The branchial osmoregulatory response of gilthead sea bream (Sparus auratus L.)
      to short-term (2-192 hr) and long-term (2 weeks) exposure to different
      environmental salinities (5 per thousand, 15 per thousand, 25 per thousand, 38
      per thousand and 60 per thousand) was investigated. A "U-shaped" relationship was
      observed between environmental salinity and gill Na+,K+ -ATPase activity in both
      long- and short-term exposure to altered salinity, with the increase in activity
      occurring between 24 and 96 hr after the onset of exposure. Plasma osmolality and
      plasma ions (sodium, chloride, calcium and potassium) showed a tendency to
      increase in parallel with salinity. These variables only differed significantly
      (P<0.05) in fish adapted to 60 per thousand salinity with respect to fish adapted
      to full-strength sea-water (SW). Plasma glucose remained unchanged whereas plasma
      lactate was elevated at 5 per thousand and 60 per thousand. Muscle water content
      (MWC) was significantly lower in fish adapted to 60 per thousand. Chloride cells
      (CC) were only present on the surface of the gill filaments and absent from the
      secondary lamellae. CC distribution was not altered by external salinity.
      However, the number and size of CC were significantly increased at salinity
      extremes (5 per thousand and 60 per thousand), whereas fish exposed to
      intermediate salinities (15 per thousand and 25 per thousand) had fewer and
      smaller cells. Furthermore, the CC of fish exposed to diluted SW became rounder
      whereas they were more elongated in fish in full-strength and hypersaline SW.
      This is consistent with previous reports indicating the existence of two CC types
      in euryhaline fish. At likely environmental salinities, gilthead sea bream show
      minor changes in plasma variables and the effective regulation of gill Na+,K+ 
      ATPase. However, at very low salinities both haemodilution and up-regulation of
      gill Na+,K+ -ATPase predict a poor adaptation most likely related to deficiency
      or absence of specific components of the CC important for ion xuptake.

PMID- 15945080
TI  - Sexual size dimorphism and growth plasticity in snakes: an experiment on the
      Western Diamond-backed Rattlesnake (Crotalus atrox).
AB  - We conducted an experiment to examine the effects of sex and food intake on
      growth, mass gain, and attainment of sexual maturity in Western Diamond-backed
      Rattlesnakes (Crotalus atrox). We also measured testosterone levels to determine
      whether testosterone might be involved in the male-biased sexual size dimorphism
      observed in this species. We collected neonate rattlesnakes and raised them in
      the laboratory for 2 years on either a high-intake diet (fed one mouse per week)
      or a low-intake diet (fed one mouse every 3 weeks). High-intake snakes grew and
      gained mass more rapidly than low-intake snakes, but males did not grow or gain
      mass more rapidly than females in either treatment group. High-intake snakes
      attained reproductive maturity earlier than low-intake snakes, indicating that
      size, not age, is the critical determinant of reproductive maturity. Males had
      higher levels of testosterone than females but did not grow more quickly,
      suggesting that testosterone may not affect growth in this species and may
      therefore not be the proximate determinant of sexual size dimorphism.

PMID- 15945081
TI  - Utility of CD10 and RCCma in the diagnosis of metastatic conventional renal-cell
      adenocarcinoma by fine-needle aspiration biopsy.
AB  - The cytologic diagnosis of primary conventional renal-cell adenocarcinoma (cRCC)
      is usually straightforward; however, metastatic cRCC must be distinguished from a
      variety of neoplasms with clear-cell features. CD10, a cell membrane-associated
      neutral endopeptidase, and renal-cell carcinoma marker (RCCma), an antibody
      against human proximal tubular brush border antigen, have recently been shown to
      be useful in the diagnosis of cRCC. We compared CD10 and RCCma in cell block
      material from fine-needle aspiration biopsies (FNABs) to assess their utility in
      the diagnosis of metastatic cRCC, in cytologic specimens. Seven primary and
      sixteen metastatic cRCCs were immunostained with CD10 and RCCma. The
      immunoreactivity results were compared with those of a variety of neoplasms
      originating from other sites such as the liver, lungs, breast, and the
      gastrointestinal tract. The sensitivity and specificity of CD10 for cRCC were
      100% and 59%, respectively. The sensitivity and specificity of RCCma for cRCC
      were 35% and 100%, respectively. We conclude that CD10 has limited value in
      confirming the diagnosis of cRCC because of its low specificity. RCCma, when
      positive, is highly specific for cRCC, but its low sensitivity hinders its
      diagnostic usefulness.

PMID- 15945082
TI  - MIB-1 and PCNA immunostaining as a diagnostic adjunct to cervical Pap smear.
AB  - The present study was done to determine the role of MIB-1 (Molecular Immunology
      Borstel) and proliferating cell nuclear antigen (PCNA) proliferative index as a
      diagnostic adjunct to cervical Papanicolaou (Pap) smear for the identification of
      ascending grades of cervical intraepithelial neoplasia (CIN) developing into
      cancer in the human uterine cervix. A total of 49 adequate Pap smears with
      consensus diagnosis were destained for immunocytochemical staining (MIB-1 and
      PC10). Staining was done by streptavidin-biotin method after antigen retrieval.
      MIB-1 and PC10 labeling index (LI) were calculated in each case and divided into
      three groups, i.e., <10%, 10-20%, and >20%, respectively. Statistical analysis
      was done by using the SPSS 10.0 package. The comparisons were made using analysis
      of variance (ANOVA) and independent sample t-test. Bivariate and Pearson's
      correlation coefficient were used to obtain correlations between different
      groups. Out of 49 cases, 40 cases (81.6%) showed positive immunostaining with MIB
      1 and PCNA. Proliferative LI of MIB-1 and PCNA increased with the ascending
      grades of CIN lesions to carcinoma. The highest proliferative index (mean +/- SD)
      for PCNA and MIB-1 were observed for the carcinoma group (PCNA LI, 39.200 +/-
      1.6865; MIB-1LI, 35.300 +/- 1.8886). A significant positive correlation between
      ascending grades of squamous intraepithelial lesion (SIL) and labeling indices of
      markers (r = 0.87 for MIB-1 and r = 0.88 for PCNA) suggests that MIB-1/PCNA
      proliferative markers can be used as an adjunct to cytomorphological
      interpretation of conventional cervical Pap smear.

PMID- 15945083
TI  - Diagnostic accuracy of imprint cytology in the assessment of Hodgkin's disease in
      Japan.
AB  - Our objective was to evaluate the usefulness of cytomorphologic assessment in the
      accuracy of diagnosis of Hodgkin's disease (HD), using imprint cytological
      preparations over a 18-yr period. Imprint materials from 34 HD cases were
      reviewed using cytomorphological and immunocytochemical studies. Twenty-six cases
      (76.5%) were diagnosed to be HD and 6 cases (17.6%) were suspected to be HD, but
      2 cases (5.9%) were cytologically diagnosed as reactive lesions, because of an
      insufficient number of Reed-Sternberg (RS) cells. The 6 suspected cases were
      definitively diagnosed as HD, using immunocytochemistry. Immunophenotyping of RS
      cells in 32 cases (excluding the two cases of reactive lesions) showed CD30+ in
      31 (96.9%) cases, CD15+ in 22 (68.8%) cases and CD20+ in 12 (37.5%) cases. RS
      cells were immunophenotypically classified into five groups: A, (CD 30+, 15+, 20
      ) 15 (46.9%); B, (CD30+, 15-, 20-) 5 (15.6%); C, (CD 30+, 15+, 20+) 6 (18.8%); D,
      (CD30+, 15-, 20+) 5 (15.6%); and E, (CD30-, 15+, 20+) 1 (3.1%). Cytomorphologic
      differences in RS cells were identified between group D and other groups (CD15+
      and/ or CD20-). The former had a low polymorphic shape (like popcorn), and the
      latter had a more classical polymorphic shape. Epstein-Barr virus (EBV)-latent
      membrane protein-1(LMP-1) was identified in 16 (50%) cases. LMP-1 expression was
      found not only in classic RS cells, but also in smaller variants. These variants
      did not match the morphologic criteria of RS cells, but expressed the common
      phenotype (CD30+, CD15+/-) of RS cells, suggesting the same cellular origin as RS
      cells. This study demonstrated that imprint cytology from lymph node biopsies can
      be a useful tool for the diagnosis and the evaluation of the cellular biology of
      HD.

PMID- 15945084
TI  - Metastatic mammary carcinomas with endocrine features: potential diagnostic
      pitfalls.
AB  - Mammary carcinomas with endocrine differentiation (MCED) are an uncommon subtype
      of breast carcinomas that are morphologically indistinguishable from low-grade
      endocrine neoplasms arising in other organs. Aspirates of MCED yield relatively
      monotonous cells with eccentrically placed nuclei containing characteristic "salt
      and pepper" chromatin. In the breast, these features represent MCED. In
      extramammary sites, the differential is more extensive, and diagnosing MCED
      metastases to the lung, a common location for primary and metastatic endocrine
      tumors, can be a challenging task, with significant clinical implications.
      Although primary MCED have been described extensively in the cytology literature,
      secondary pulmonary MCED have not been reported to the best of our knowledge. We
      report three cases of MCED metastatic to the lung and present the cytological and
      immunohistochemical features.

PMID- 15945085
TI  - Metastatic lobular carcinoma in a ThinPrep Pap test: cytomorphology and
      differential diagnosis.

PMID- 15945086
TI  - Determining competency and proficiency in cytology: who decides?

PMID- 15945087
TI  - Small-cell tumors of the liver: a cytological study of 91 cases and a review of
      the literature.
AB  - This study was designed to consider the cytomorphological spectrum, differential
      diagnosis, and the role of ancillary studies in small-cell tumors of the liver.
      Three independent pathologists reviewed cytological slides from 91 cases of small
      cell tumors of the liver. The results were compared with the findings of three
      recently published studies (Cytopathology 11 (2000) 262-267; Diagn Cytopathol 19
      (1998) 29-32; and Acta Cytol 40 (1996) 937-947). The role of immunohistochemistry
      in reaching timely and specific diagnoses was also examined. The diagnostic
      categories included 44 cases of metastatic small-cell undifferentiated carcinoma,
      15 cases of metastatic neuroendocrine carcinoma, 10 cases of metastatic
      adenocarcinoma, 7 cases of malignant lymphoma, 4 cases of hepatocellular
      carcinoma with small-cell features, 2 cases of cholangiocarcinoma, 1 case of
      poorly differentiated carcinoma, and 8 cases of rare tumors including granulosa
      cell tumor (2 cases), sarcoma (4 cases), malignant melanoma with small-cell
      features (1 case), and meningioma with small-cell features (1 case). Metastatic
      granulosa cell-tumor, metastatic melanoma, and metastatic meningioma should be
      included in the differential diagnoses of small-cell malignancies found in the
      liver.

PMID- 15945088
TI  - Sampling of the adrenal glands by endoscopic ultrasound-guided fine-needle
      aspiration.
AB  - Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) has proven to be
      a valuable modality for the primary diagnosis and staging of gastrointestinal,
      and perigastrointestinal malignancy. Aside from assessing thoracic and abdominal
      lymph nodes and the liver for metastases, EUS can assess and sample the adrenal
      glands, which are frequently involved by metastatic disease, but can also harbor
      benign primary neoplasms. The cytology files at our institution were reviewed for
      all cases of EUS-guided FNA of the adrenal glands. Clinical histories,
      sonographic findings, and cytologic findings of all cases were reviewed. Results
      were compared with overall EUS-guided FNA performance and the performance of non
      EUS-guided FNA of the adrenal. The utility of cell block immunohistochemistry
      (IHC) in these cases was reviewed. Between 1/1/00 and 5/15/04 there were 24 cases
      of EUS-guided FNA of the adrenal gland from 22 different patients (13 men; 9
      women) at our institution. This represented 1.4% of overall EUS-guided FNA and
      77% of adrenal gland FNA. Patient ages ranged from 37 to 86 yr (mean 69 +/- 11
      yr). Most patients had other cancers or mass lesions and were being staged at the
      time of the procedure (19 of 22). Almost all FNAs were of the left adrenal gland
      (23 of 24). Lesion size ranged from 0.9 to 7.9 cm (mean 2.5 +/- 1.6 cm).
      Diagnostic material was present in all cases when compared with an overall EUS
      guided FNA diagnostic rate of 88%. Material for cell block was present in 21
      cases, and IHC was used in 3 cases. Final diagnoses were as follows: cortical
      tissue consistent with cortical adenoma (19), metastatic adenocarcinoma (3),
      pheochromocytoma (1), and adrenal cortical carcinoma (1). EUS-guided FNA of the
      adrenal gland is primarily used in the staging of other malignancies when lesions
      of the left adrenal are recognized sonographically. Diagnostic tissue is easily
      obtained, including material for cell block IHC, which allows definitive
      diagnosis in cases that present difficult differential diagnoses.

PMID- 15945089
TI  - Diagnosis of Strongyloides stercoralis in a routine cervical smear.

PMID- 15945090
TI  - Chest wall abscess: an unusual presentation of Hodgkin's lymphoma.
AB  - A chest wall abscess is a very rare presentation of extranodal Hodgkin's lymphoma
      (HL); only one case has been reported to date. Here, we describe a case of a 38
      yr-old man with HL whose initial presentation was a chest wall abscess. The
      diagnosis of HL was suggested by cytological examination of the purulent
      discharge and was confirmed subsequently by excisional biopsy of cervical lymph
      node.

PMID- 15945091
TI  - Cryptococcal parotitis presenting as a cystic parotid mass: report of a case
      diagnosed by fine-needle aspiration cytology.
AB  - We report the fine needle aspiration (FNA) cytology findings that allowed us to
      diagnose cryptococcal parotitis in a 31-year-old HIV positive patient. The
      patient presented with painful and enlarged right parotid gland and a CT scan
      showed a cystic lesion with rim enhancement. The FNA cytology revealed yeasts of
      variable size, some of which had bright eosinophilic capsules in Diff-Quik
      stained preparations. Mucicarmine and silver stain supported the diagnosis of
      cryptococcal parotitis, which was later confirmed by fungal culture of the
      aspirated material. We thus show that fungal infection can present as a cystic
      parotid mass in an immunosuppressed patient and that the diagnosis can be made by
      FNA cytology.

PMID- 15945092
TI  - Cytomorphologic features of immature ovarian teratoma in peritoneal effusion: a
      case report.
AB  - We describe unusual cytologic features of the peritoneal fluid in a patient with
      immature ovarian teratoma. Immature embryonal and neuroectodermal components of
      such tumors are rarely observed in the ascites; to our knowledge, there have been
      only three reports of cytologic findings of immature teratoma cells in the
      ascites. Our patient was a 26-yr-old woman who presented with a huge pelvic mass.
      A grade 3 immature right ovarian teratoma was diagnosed pathologically. Cytologic
      examination of the ascitic fluid revealed a variety of neoplastic cells,
      including immature neuroepithelial cells forming rosette-like structures,
      keratinized squamous cells, squamoid metaplastic cells, and immature glial
      appearing cells. Immunohistochemical analysis revealed that immature
      gastrointestinal elements and yolk sac elements were positive for alpha
      fetoprotein. This is the first description of the cytologic features of non
      neuroepithelial elements in the ascitic fluid in a patient with immature ovarian
      teratoma.

PMID- 15945094
TI  - Cytomorphological features of a metastatic myoepithelial carcinoma arising in a
      minor salivary gland.

PMID- 15945093
TI  - Interdigitating dendritic reticulum cell sarcoma: cytologic, histologic and
      immunocytochemical features.
AB  - Tumors of dendritic reticulum cells are rare neoplasms that exhibit significant
      morphologic overlap with other malignancies. Fine-needle aspiration cytologic
      appearances of this neoplasm are not well understood. A 33-yr-old woman presented
      with a rapidly growing nodular mass in the right upper cervical region and right
      sided ptosis. Fine-needle aspiration cytology of the mass showed dissociated as
      well as clustered, large, polygonal cells that showed high nuclear-cytoplasmic
      ratio. Nuclei were round, oval, or irregular in shape. Large and small blastoid
      forms with prominent nucleoli and chromatin clumping as well as binucleated cells
      and cells with lobulated nuclei were seen. Numerous mitoses were observed. The
      tumor cells expressed focal immunocytochemical reactivity to CD45 and CD68, but
      were negative for CD2, CD3, CD4, CD8, CD20, CD30, CD45RO, epithelial membrane
      antigen (EMA), cytokeratin, and HMB45. Histologic sections of the biopsy from the
      growth showed nodal tissue effaced by a tumor composed of large, pleomorphic
      neoplastic cells with some binucleate and multinucleate forms resembling Reed
      Sternberg cells. The intervening stroma contained numerous small lymphocytes.
      Tumor cells expressed vimentin, S-100 protein, CD68, and MAC387, but were
      negative for LCA, CD1a, CD3, CD15, CD20, CD21, CD23, CD30, CD35, carcino
      embryonic antigen, HMB45, cytokeratin AE1/3, EMA, myeloperoxidase, lysozyme,
      smooth-muscle actin, and desmin. The combined histologic and immunohistologic
      features suggested a histiocytic/dendritic reticulum cell neoplasm and a
      diagnosis of interdigitating dendritic reticulum cell sarcoma was made.

PMID- 15945095
TI  - Endometriosis of the kidney: diagnosis by fine-needle aspiration cytology.

PMID- 15945096
TI  - Chromosome 22 tiling-path array-CGH analysis identifies germ-line- and tumor
      specific aberrations in patients with glioblastoma multiforme.
AB  - Gliomas are common and frequently malignant tumors of the central nervous system.
      Recurrent allelic losses of chromosome 22 have been reported in gliomas,
      indicating tumor-suppressor genes at this location. However, the target genes are
      still unknown. We applied a high resolution tiling-path chromosome 22 array to a
      series of 50 glioblastoma samples, with the aim of investigating the underlying
      abnormalities in both constitutional and tumor-derived DNA. We detected
      hemizygous deletions in 28% of the tumors (14 of 50), with monosomy 22 (10 of 50)
      being the predominant pattern. The distribution of overlapping hemizygous
      deletions delineated two putative tumor-suppressor loci (11.1 and 3.08 Mb in
      size) across 22q. Most strikingly, we identified two distinct loci affected by
      regional gains. Both alterations were of germ-line origin and were unique to
      samples from patients affected with tumors. Analysis of these two amplified
      regions revealed the presence of two interesting candidate genes: TOP3B and
      TAFA5. The TOP3B gene encodes a protein that seems to function in the unlinking
      of parental strands at the final stage of DNA replication and/or in the
      dissociation of structures in mitotic cells that could lead to recombination. The
      TAFA5 gene belongs to a novel family of proteins with similarity to chemokines
      and brain-specific expression. The role of the identified candidate loci should
      be studied further. Our results demonstrated the power of array-CGH to determine
      DNA copy number alterations in the context of germ-line- and tumor-specific
      aberrations.

PMID- 15945097
TI  - Proteasome inhibitors can alter the signaling pathways and attenuate the P
      glycoprotein-mediated multidrug resistance.
AB  - Numerous signaling pathways were reported to be involved in the resistance for
      conventional cytotoxic drugs, although one of the main reasons is the
      overexpression of P-glycoprotein (P-gp) in multidrug resistant cancer cells. The
      overexpression of P-gp has been associated with the resistance to a wide range of
      anticancer drugs. Doxorubicin and paclitaxel are substrates of this transporter
      system and have an important role for the various human malignancies. In the
      present study, drug-sensitive MCF7 and multidrug resistant MCF7/ADR
      (characterized by overexpression of P-gp) human breast cancer cell lines were
      used as an experimental model. We have found that PS341 and MG132, proteasome
      inhibitors, reduced the degree of the multidrug resistance (MDR) in MCF7/ADR
      cells. This phenomenon was accompanied by a decrease in the IC50 value of
      doxorubicin and paclitaxel from 55.9 +/- 3.46 to 0.60 +/- 0.08 microM, and from
      17.61 +/- 1.77 to 0.59 +/- 0.12 microM, respectively. The IC50 values of
      sensitive cells for doxorubicin and paclitaxel were about 0.42 and 0.83 microM,
      respectively. The effect of PS341 and MG132 on MCF7/ADR cells was associated with
      a significant decrease in both protein and gene levels of P-gp expression.
      Moreover, with regard to the expression of possible signal transduction pathways
      of mitogen-activated protein kinase (MAPK) related to the activation of mdr1,
      proteasome inhibitors did significantly influence the activation of these
      proteins. Western blot analysis revealed that 24 hr exposure of multidrug
      resistant MCF7/ADR cells with proteasome inhibitors did change the levels of DNA
      binding activity of nuclear factor-kappaB (NF-kappaB), pERK1/2, c-Jun, and p-c
      Jun. In conclusion, we could remark that proteasome inhibitors (especially PS341)
      attenuate the resistance of MCF7/ADR cells for P-gp substrate drugs of
      doxorubicin and paclitaxel. Several proteins are supposed to be associated with
      the resensitization of the cells to conventional cytotoxic drugs, although
      decreased activity of P-gp is at least involved in the proteasome inhibitor
      related resensitization. And influence with MAPK pathways, which have been
      reported to be associated with the regulation of P-gp, might be contributed to
      the resensitization brought by proteasome inhibitors.

PMID- 15945098
TI  - Induction of antigen-specific CD4- and CD8-mediated T-cell responses by fusions
      of autologous dendritic cells and metastatic colorectal cancer cells.
AB  - Human metastatic colorectal carcinomas (CRCAs) express carcinoembryonic antigen
      (CEA) and/or MUC1 tumor-associated antigens as potential targets for the
      induction of active specific immunity. In the present study, freshly isolated
      metastatic CRCA cells were successfully fused with immature autologous human
      monocyte-derived dendritic cells (DCs). The created heterokaryons (DC/CRCA)
      coexpress the CRCA-derived CEA and MUC1 antigens and DC-derived MHC class II and
      costimulatory molecules. The fusion cells were functional in stimulating the
      proliferation of autologous T cells. In addition, both CD4(+) and CD8(+) T cells
      were activated by fusion cells, as demonstrated by the production of high levels
      of IFN-gamma. More importantly, coculture of fusion cells with patient-derived
      peripheral blood mononuclear cells (PBMCs) resulted in the induction of antigen
      specific cytotoxic T lymphocytes (CTLs). CTLs were effective at lysis of not only
      autologous CRCA cells but also the CEA and/or MUC1-positive and HLA partially
      matched target cells. Antigen-specific CTL responses were confirmed by tetrameric
      analysis. Coculture of PBMCs with fusion cells resulted in increased frequency of
      CEA- and MUC1-specific CTLs simultaneously. Taken together, these results
      indicate that freshly isolated human metastatic CRCA cells expressing the CEA
      and/or MUC1 may represent a potential partner for the creation of DC/tumor fusion
      cells targeting induction of antigen-specific CTL responses. Our report
      demonstrates the simultaneous induction of CRCA-specific CTL responses restricted
      by HLA-A2 and -A24.

PMID- 15945099
TI  - Gene regulation profile reveals consistent anticancer properties of progesterone
      in hormone-independent breast cancer cells transfected with progesterone
      receptor.
AB  - Absence of estrogen receptor (ER) and progesterone receptor (PR) is the hallmark
      of most hormone-independent breast cancers. Previous studies demonstrated that
      reactivation of PR expression in hormone-independent MDA-MB-231 breast cancer
      cells enabled progesterone to suppress cell growth both in vitro and in vivo. We
      determined the whole genomic effect of progesterone in PR-transfected MDA-MB-231
      cells. We identified 151 progesterone-regulated genes with expression changes > 3
      fold after 24 hr treatment. Most are novel progesterone target genes. Real-time
      RT-PCR analysis of 55 genes showed a 100% confirmation rate. Twenty-six genes
      were regulated at both 3 and 24 hr. Studies using translation inhibitor suggest
      that most of the 26 genes are primary progesterone target genes. Progesterone
      consistently suppressed the expression of genes required for cell proliferation
      and metastasis and increased the expression of many tumor-suppressor genes.
      Progesterone also consistently decreased the expression of DNA repair and
      chromosome maintenance genes, which may be part of the mechanism leading to cell
      cycle arrest. These data suggest potential usefulness of progestin in combating
      ER-negative but PR-positive breast cancer and indicate that progesterone can
      exert a strong anticancer effect in hormone-independent breast cancer following
      PR reactivation. The identification of many novel progesterone target genes open
      up new avenues for in-depth elucidation of progesterone-mediated molecular
      networks.

PMID- 15945100
TI  - The melanoma-associated 24 base pair duplication in p16INK4a is functionally
      impaired.
AB  - Melanoma-associated germline mutations affecting the tumor suppressor and cyclin
      dependent kinase (CDK) inhibitor, CDKN2A/p16INK4a, have been identified in over
      100 melanoma-prone families worldwide. To predict the melanoma risk for carriers
      of specific mutations, mutant p16INK4a can be tested in biochemical and cellular
      assays. In most cases, p16INK4a mutations with predicted disease relation, due to
      segregation with melanoma, are functionally impaired in such assays. The N
      terminal 24 base pair duplication of CDKN2A, however, encodes a p16INK4a variant
      previously shown to have wild-type function, despite segregating with melanoma in
      at least 5 melanoma families. To clarify whether the duplication mutation has a
      cell cycle regulatory defect or behaves like wild-type p16INK4a, we reanalyzed
      the cell cycle-inhibitory activity of this mutation. Stable cell clones of the
      p16-null WMM1175 melanoma cell line inducible for ectopic p16INK4a were used in
      this study. In these cells, p16INK4a expression can be controlled at physiologic
      levels. Our results show that in comparison to wild-type p16INK4a, the
      duplication mutant induced weaker S-phase inhibition and cells expressing this
      mutant form of p16INK4a retained colony formation ability. We also show that the
      cell cycle-regulatory defect of the p16INK4a duplication mutant was associated
      with decreased inhibition of pRb phosphorylation even though it retained
      significant binding to CDK4.

PMID- 15945101
TI  - Phase 1/2 study of subcutaneous and intradermal immunization with a recombinant
      MAGE-3 protein in patients with detectable metastatic melanoma.
AB  - The purpose of this phase 1/2 study was to evaluate toxicity, tumor evolution and
      immunologic response following administration of a fixed dose of a recombinant
      MAGE-3 protein by subcutaneous and intradermal routes in the absence of
      immunologic adjuvant. Thirty-two patients with detectable metastatic melanoma
      expressing gene MAGE-3 were included and 30 received at least one injection with
      a fixed dose of a ProtD-MAGE-3 fusion protein. The immunization schedule included
      6 intradermal and subcutaneous injections at 3-week intervals. Afterward,
      patients without major tumor progression who required other treatments received
      additional vaccinations at increasing time intervals. The vaccine was generally
      well tolerated. Among the 26 patients who received at least 4 vaccinations, we
      observed 1 partial response and 4 mixed responses. For these 5 responding
      patients, time to progression varied from 3.5 to 51+ months. An anti-MAGE-3 CD4 T
      lymphocyte response was detected in 1 out of the 5 responding patients. The
      majority of patients had no anti-MAGE-3 antibody response. The clinical and
      immunologic responses generated by the vaccine are rather limited. Nevertheless,
      given the potential antitumor efficacy and the very mild toxicity of
      vaccinations, further studies combining MAGE proteins and/or peptides with potent
      immunologic adjuvants are warranted, not only in metastatic melanoma, but also in
      the adjuvant setting.

PMID- 15945102
TI  - Meta-analysis of soy food and risk of prostate cancer in men.
AB  - There has been considerable interest in recent years in the role of soy in cancer
      etiology. The purpose of this meta-analysis was to evaluate epidemiologic studies
      available to date that related soy consumption to the risk of prostate cancer in
      men. We conducted a thorough Medline search for English-language publications,
      supplemented with hand-searching of articles' bibliographies and nonindexed
      medical and professional journals, on epidemiologic studies of soy and prostate
      cancer. We identified 2 cohort and 6 case-control studies that met the following
      criteria for meta-analysis: a study must have assessed soy as a food and provided
      a risk estimate (relative risk or odds ratio) and its 95% confidence interval.
      Data from the same study population appearing in different journals were only
      used once with the most recent publication chosen for the analysis. Studies on
      fermented soy food were not included. We conducted the meta-analysis using a
      random-effects model. An analysis of these studies yielded an overall risk
      estimate of 0.70 (95% CI = 0.59-0.83; p < 0.001). No publication bias was
      detected. In summary, results of the analysis showed that consumption of soy food
      was associated with a lower risk of prostate cancer in men.

PMID- 15945103
TI  - Two cases of late embolization of Amplatzer septal occluder devices to the
      pulmonary artery following closure of secundum atrial septal defects.
AB  - The Amplatzer septal occluder (ASO; AGA Medical Corporation) is a self-expanding
      nitinol double-disk device that is being used for atrial septal defect closure
      with increasing frequency. The morbidity of the procedure is thought to be low,
      but complications are possible. We describe two cases of delayed embolization of
      the device to the right heart. Our patients both required surgical retrieval of
      the devices, which had migrated to the pulmonary artery.

PMID- 15945104
TI  - Technique of left main stenting is dependent on lesion location and distal branch
      protection.
AB  - The purpose of this study was to review our experience with left main stenting
      and evaluate initial results with drug-eluting stents (DESs). Drug-eluting stents
      delivered with contemporary techniques could change the traditional surgical
      approach to patients with significant left main disease. One hundred sixty-one
      patients underwent left main stenting (100 bare metal, 61 drug-eluting) after
      being excluded from surgery. In group A, disease was confined to the ostium or
      main stem; in group B, disease involved the bifurcation. Patients were classified
      as either unprotected (U) or protected (P) depending on the presence of a patent
      bypass graft. Study endpoints were any major adverse cardiac event (MACE). In
      hospital MACE was 6% with no deaths; 74% of patients in group A underwent direct
      stenting, whereas 89% of the patients in group B had predilatation performed
      prior to stent implantation. A total of 98% of patients in BU had kissing balloon
      inflations after stent deployment; provisional side-branch stenting was required
      in one patient. V-stenting was performed in 13% of patients in group BU. The 1
      year mortality in the bare metal stent group was 9% with the majority of deaths
      in group BU. There was one noncardiac death in the DES group at 6 months and five
      patients (8.2%) underwent target vessel revascularization for restenosis. Event
      free survival at 6 months in group BU treated with DESs was 87%. Significant left
      main disease presents a spectrum of angiographic abnormalities and different
      interventional techniques are required depending on lesion location and distal
      protection. Although in-hospital complications with left main stenting were low
      in this single-center study, follow-up events were common in patients treated
      with bare metal stents. A randomized multicenter trial will be required to
      determine whether drug-eluting stents will improve survival in patients with left
      main disease.

PMID- 15945105
TI  - Brief repetitive balloon occlusions enhance reperfusion during percutaneous
      coronary intervention for acute myocardial infarction: a pilot study.
AB  - The objective of this study was to determine whether acutely ischemic myocardium
      may be conditioned during percutaneous coronary intervention for acute myocardial
      infarction. Ischemic preconditioning is a powerful cardioprotective mechanism
      that limits infarct size in animal investigations and ischemic sequelae during
      percutaneous coronary intervention in man. However, the conditioning stimulus in
      all these studies has been applied prior to the defining episode of ischemia.
      Seventeen patients undergoing percutaneous coronary intervention for acute
      myocardial infarction were randomly assigned to a standard ischemic
      preconditioning protocol (n = 10) or a usual-care control group (n =7). ST
      segment shift response and Doppler-derived distal coronary velocity data were
      compared. Despite similar degrees of baseline ST segment elevation, the magnitude
      of final ST segment elevation in the conditioning group was less than that in
      controls at the protocol conclusion (conditioning, 1.60 +/- 0.8 mV; control, 4.0
      +/- 0.5 mV; P < 0.001). The rate of ST segment resolution was greater in the
      conditioning group (conditioning, 0.28 +/- 0.1 mV/min; control, 0.12 +/- 0.1
      mV/min; P = 0.02). Distal coronary velocimetry indicated significant improvement
      in coronary flow velocity reserve in the conditioning group at the protocol
      conclusion (conditioning, 1.8 +/- 0.2; control, 1.4 +/- 0.1; P < 0.008). Brief
      periods of occlusion and reperfusion during percutaneous intervention for acute
      myocardial infarction mitigate the extent of ischemic injury and improve distal
      myocardial perfusion. Such ischemic conditioning represents a potentially useful
      adjunct to strategies for enhancing reperfusion during acute myocardial
      infarction.

PMID- 15945106
TI  - Endovascular stenting of nonmalignant superior vena cava syndrome.
AB  - Superior vena cava (SVC) syndrome is associated with advanced malignancy of the
      chest. Extensive experience is published in the literature regarding the use of
      endovascular intervention for symptomatic relief in these individuals with
      limited survival. Symptomatic SVC obstruction may occur from benign conditions
      that may not alter life expectancy. There are few data regarding endovascular
      therapy in this setting. We retrospectively analyzed our experience using
      endovascular intervention for benign SVC obstruction in 19 patients. In our
      series, the mean age was 46.4 years; 58% were female and 14/19 cases were due to
      an intravascular device. All patients experienced symptomatic relief. Median
      follow-up was 28.8 months. Three patients required secondary procedures to
      maintain patency. Four patients had procedural complications, which did not
      affect the outcomes. One patient died from complications of anticoagulation at 24
      months. Endovascular procedures aimed at relieving SVC stenosis seem to be
      effective in patients with benign disease.

PMID- 15945107
TI  - Percutaneous left ventricular assist device: "TandemHeart" for high-risk coronary
      intervention.
AB  - Patients undergoing percutaneous coronary intervention (PCI) with severely
      compromised left ventricular systolic function and complex coronary lesions,
      including multivessel disease, left main disease, or bypass graft disease, are at
      higher risk of adverse outcomes from hemodynamic collapse. The TandemHeart
      percutaneous ventricular assist device may provide circulatory support during
      high-risk PCI. We implanted the TandemHeart device in eight patients who
      underwent high-risk PCI. The patients were considered to be at exceptionally high
      risk for decompensation due to procedural complexity combined with underlying LV
      dysfunction. The mean ejection fraction was 30% +/- 9% and five patients were
      turned down for surgical revascularization. Seven patients underwent multivessel
      PCI, including three patients who underwent unprotected left main coronary artery
      PCI. There was 100% procedural success. The TandemHeart was removed immediately
      post-PCI with no groin complications. Six patients are event- and symptom-free at
      189 +/- 130 days; one patient died 10 days post-PCI after lower extremity bypass
      surgery and another developed acute renal failure postprocedure, requiring
      hemodialysis. Our initial clinical experience with the TandemHeart ventricular
      assist device demonstrates that hemodynamic support can be rapidly achieved
      percutaneously during high-risk PCI, with excellent procedural success in highly
      complex and critically ill patients.

PMID- 15945108
TI  - Texture effects of circularly ordered fibers.
AB  - Powder samples can show pronounced texture effects in X-ray scattering. Here,
      texture effects are described theoretically for circularly ordered fibers and
      shown experimentally for a special type of these fibers based on nanostructured
      silica. The systematic diffraction peak intensity dependences, observed with the
      tilting of the samples, fit well with the theoretical model proposed and can be
      used as an efficient detection method for circulite-type mesopore organization.
      Our investigations clearly emphasize the difficulties encountered in the
      interpretation of peak intensities in the X-ray scattering analyses because of
      pronounced texture effects.

PMID- 15945109
TI  - Zn-porphyrin-sensitized nanocrystalline TiO2 heterojunction photovoltaic cells.

PMID- 15945110
TI  - Recent advances in catalytic, enantioselective alpha aminations and alpha
      oxygenations of carbonyl compounds.
AB  - The direct introduction of either a nitrogen or oxygen atom adjacent to a
      carbonyl group in a catalytic, enantioselective manner using both chiral Lewis
      acid and Lewis base catalysis has been described recently. The enantiomerically
      enriched products of these reactions, such as alpha-amino acids, represent
      fundamental building blocks for the construction of complex natural products and
      other important bioactive molecules. This Minireview provides a synopsis of this
      ever-growing field and highlights some of the challenges that still remain.

PMID- 15945111
TI  - cyclo-Ti3[eta2(mu2-C,O)]3: a side-on-bonded polycarbonyl titanium cluster with
      potentially antiaromatic character.

PMID- 15945113
TI  - Recent progress in asymmetric allylic substitutions catalyzed by chiral copper
      complexes.

PMID- 15945112
TI  - A regenerative chemodosimeter based on metal-induced dye formation for the highly
      selective and sensitive optical determination of Hg2+ ions.

PMID- 15945114
TI  - A DNAzyme that walks processively and autonomously along a one-dimensional track.

PMID- 15945115
TI  - A high-precision switch on an RNA message.

PMID- 15945116
TI  - Aptamer-directed self-assembly of protein arrays on a DNA nanostructure.

PMID- 15945117
TI  - Electron spin resonance--a spectroscopic method for determining the antioxidative
      activity.

PMID- 15945118
TI  - Assay of advanced glycation endproducts in selected beverages and food by liquid
      chromatography with tandem mass spectrometric detection.
AB  - Food and beverages contain protein glycation adducts--both early-stage adducts
      and advanced glycation endproducts. We determined the concentrations of glycation
      adducts in selected food and beverages by liquid chromatography with triple
      quadrupole mass spectrometric detection. Cola drink contained low concentrations
      of glycation free adducts, whereas pasteurised and sterilised milk were rich
      sources of heat-stable glycation adduct residues--Nepsilon-carboxymethyl-lysine
      and Nepsilon-carboxyethyl-lysine. Laboratory rodent food was a rich source of
      advanced glycation endproducts. Measurement of glycation adducts in 24 h urine
      samples of normal and diabetic rats indicated that < 10% of glycation adduct
      residue consumption was excreted. Induction of diabetes by streptozotocin led to
      a 2-fold increase in urinary excretion of Nepsilon-carboxymethyl-lysine and a 27
      fold increase in urinary excretion of methylglyoxal-derived hydroimidazolone
      Ndelta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine - the latter was decreased
      by high-dose thiamine therapy that also prevented the development of nephropathy.
      We conclude that cola drinks are a poor source of glycation adduct whereas
      thermally processed milk is rich in glycation adducts. Dietary glycation adducts
      residues probably have low bioavailability. Experimental diabetes is associated
      with a marked increase in exposure to endogenous formation of methylglyoxal
      derived hydroimidazolone which is linked to the development of diabetic
      nephropathy.

PMID- 15945119
TI  - Factors affecting elimination of polycyclic aromatic hydrocarbons from smoked
      meat foods and liquid smoke flavorings.
AB  - This review deals with effects of environmental and physicochemical factors
      affecting polyaromatic hydrocarbon (PAH) elimination from smoked meat products
      and liquid smoke flavoring (LSF). In the introductory part, some essential
      information are aimed at principles of food smoking and PAH formation during
      smoke generation as a result of incomplete wood combustion. Also, an application
      of alternative technology for food aromatization using LSF is briefly mentioned.
      Similarly, latest European legislation, biological effects, and analytical
      aspects of PAHs are mentioned concisely. The main part is devoted to
      physicochemical factors affecting the PAH content in smoked meat products, such
      as light, additional cooking, and packaging, which are able to decrease
      considerably PAH content in some meat products. The most important effect on PAH
      concentration decrease in LSF has low-density polyethylene (LDPE) package due to
      sorption processes on a surface of the plastic with subsequent diffusion into the
      plastic bulk. A less effective material is polyethylene terephthalate (PET), when
      only a surface adsorption process comes into account. Moreover, this process is
      affected also by other compounds presented in liquid media able to compete for
      the adsorption center on the PET surface.

PMID- 15945120
TI  - C- versus N-terminally linked melittin-polyethylenimine conjugates: the site of
      linkage strongly influences activity of DNA polyplexes.
AB  - BACKGROUND: One major barrier limiting the transfection efficiency of polyplexes
      is poor endosomal release, especially when small particles are applied. In an
      approach to overcome this barrier, covalent attachment of the membrane-active
      peptide all-(L)-melittin to polyethylenimine (PEI) polyplexes was found to
      enhance gene transfer efficiency. METHODS: The N-terminus of natural all-(L)- or
      non-immunogenic all-(D)-melittin was covalently coupled to PEI. In addition, two
      different all-(D)-melittin conjugates were synthesized, with PEI covalently
      attached to either the C-terminus (C-mel-PEI) or the N-terminus of melittin (N
      mel-PEI). Melittin-PEI polyplexes with particle sizes < 150 nm were generated in
      HEPES-buffered glucose and tested in transfection experiments. The membrane lytic
      activities of conjugates and polyplexes were analyzed at neutral and endosomal
      pH. RESULTS: All-(D)-melittin conjugates mediated enhanced gene expression
      similar to the natural all-(L)-stereoisomer, with up to 160-fold higher
      luciferase activity than unmodified PEI. The site of melittin linkage strongly
      influenced the membrane-destabilizing activities of both conjugates and
      polyplexes. C-mel-PEI was highly lytic at neutral pH and therefore elevated doses
      of C-mel-PEI polyplexes induced high toxicity. In contrast, N-mel-PEI was less
      lytic at neutral pH but retained higher lytic activity than C-mel-PEI at
      endosomal pH. This apparently promoted better endosomal release of N-mel-PEI
      polyplexes resulting in efficient gene delivery in different cell lines.
      CONCLUSIONS: The high potency of C-mel-PEI to destabilize membranes at neutral pH
      is presumably due to a reported destabilization mechanism proceeding through
      membrane insertion of the peptide. In contrast, N-mel-PEI is supposed to induce
      lysis by insertion-independent pore formation according to the toroidal pore
      model.

PMID- 15945121
TI  - A database of recombinant viruses and recombinant viral vectors available from
      the RIKEN DNA bank.
AB  - BACKGROUND: Viral vectors are required as gene-delivery systems for gene therapy
      and basic research. Recombinant adenoviruses (rAds) expressing genes of interest
      are being developed as research tools and many studies in vitro and in vivo have
      already been performed with such rAds. METHODS: Shuttle vectors for rAds were
      constructed with full-length cDNAs and rAds were generated in HEK293 cells by the
      COS-TPC method. The rAds and shuttle vectors were developed by the Japanese
      research community and deposited in the RIKEN DNA Bank (RDB;
      http://www.brc.riken.jp/lab/dna/en/) for distribution to the scientific
      community. The Recombinant Virus Database (RVD;
      http://www.brc.riken.jp/lab/dna/rvd/) was established at the RIKEN BioResource
      Center (BRC) in Japan as the source of information about and distribution of the
      various resources. RESULTS: The RIKEN BRC is releasing more than 300 recombinant
      viruses (RVs) and 500 shuttle vectors, as well as all related information, which
      is included in a newly established database, the RVD. The RVD consists of (i)
      information about the RVs, the inserted cDNAs and the shuttle vectors; (ii) data
      about sequence-tagged sites (STSs) that are markers of viral DNAs; and (iii)
      experimental protocols for the use of RVs. CONCLUSIONS: The new database and
      available resources should be very useful to scientists who are studying human
      gene therapy and performing related basic research. It is a web-interfaced flat
      file database that can be accessed through the internet. Moreover, all of the
      resources deposited in the RDB, which is a public facility in Japan, are
      available to researchers around the world.

PMID- 15945122
TI  - A CMV-actin-globin hybrid promoter improves adeno-associated viral vector gene
      expression in the arterial wall in vivo.
AB  - BACKGROUND: Adeno-associated virus (AAV) vectors are attractive tools for direct
      intralumenal arterial gene transfer in interventional cardiology or
      cardiovascular surgery, but clinical application has been constrained by poor
      gene expression in this setting. METHODS: To improve arterial wall gene
      expression, a hybrid promoter consisting of a cytomegalovirus (CMV) immediate
      early enhancer, a chicken beta-actin transcription start site, and a rabbit beta
      globin intron (CAG promoter) was substituted for the Rous sarcoma virus (RSV)
      promoter in an AAV type 2 vector with an alkaline phosphatase (AP) reporter gene.
      RESULTS: Intralumenal transduction of rabbit carotid arteries by an AAV2 vector
      containing a CAG promoter resulted in gene expression in a mean of > or = 80% of
      the lumenal area at 14 days following exposure, compared to < or = 25% gene
      expressing area with the RSV promoter-based control vector. The high prevalence
      of gene expression was maintained at 3, 7, 14, and 28 days. Importantly, in
      carotid arteries transduced with the CAG promoter, gene product expression was
      readily visible by the third day following transduction whereas gene expression
      was rarely seen before day 10 using the RSV promoter in the same animal model. On
      histology, AP gene expression was predominantly in vascular smooth muscle cells
      although some endothelial cell expression was also present. CONCLUSIONS:
      Substituting the CAG for the RSV promoter results in widespread gene expression,
      demonstrating efficient arterial wall transduction by AAV2 vectors. This finding
      plus the early time to gene expression hold promise for AAV vectors as agents for
      direct intralumenal arterial wall gene delivery during cardiovascular
      interventions.

PMID- 15945123
TI  - Effects of the Ad5 upstream E1 region and gene products on heterologous
      promoters.
AB  - BACKGROUND: All recombinant adenovirus vectors contain the upstream region of the
      E1A gene comprising the viral origin of replication, encapsidation signal, and
      cis-acting regulatory elements for transcription of the E1A and other early
      genes. Using different reporter genes, some previous studies demonstrated the
      maintenance of heterologous promoter specificity in the adenoviral context, while
      others reported that adenoviral sequences interfere with promoter activity.
      METHODS: Plasmid DNA-based luciferase reporter gene assays and adenovirus type 5
      (Ad5) infection were combined to examine the effect of the Ad5 (nt 1-353) element
      and/or adenoviral gene products on tissue-specific (Midkine (MK) and COX-2), cell
      cycle associated (Ki-67 and E2F1) and viral promoters (Ad5 E1, Ad5 E4 and SV40).
      As a proof of concept, data were verified in the setting of recombinant
      replication-defective and replication-competent adenoviral vectors. RESULTS:
      Viral and E2F1 promoter activities were enhanced by the Ad5 (nt 1-353) segment by
      approximately 100% and 145%, respectively, regardless of its position. A
      polyadenylation sequence (polyA) upstream of the promoter had no effect,
      confirming an enhancer element within the Ad5 (nt 1-353) segment. Ad5 (nt 1-353)
      increased COX-2 promoter activity by 146% but was blocked by an upstream polyA,
      indicating a cryptic transcription start site. When placing the reporter gene
      cassette in a replication-defective adenovirus, similar data were obtained. In
      the plasmid vector-based system, adenoviral gene products transactivated the E2F1
      and viral promoters by 194%, 19%, 67%, and 16%, respectively. Tissue-specific
      promoter activities were not significantly affected by the Ad5 (nt 1-353)
      segment, nor adenoviral gene products. In concert with these data, we were able
      to target replication-competent adenoviral vectors with the COX-2 promoter, but
      not with the cell cycle associated promotor. CONCLUSIONS: The adenovirus E1A
      upstream regulatory region and gene products interact with some but not all
      heterologous promoters. Often, the basal promoter activity can be reduced with an
      upstream polyA. Since the data obtained in our plasmid vector-based assay with
      internal control and infection with adenovirus could be confirmed in the
      adenoviral setting, our system might be suitable to speed up the identification
      of promoters which maintain their specificity in the adenoviral context and
      circumvent the problems associated with determining infectious adenovirus titers.

PMID- 15945124
TI  - Adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene
      transfer and improvement of transduction efficiency.
AB  - BACKGROUND: Gene therapy is an attractive new approach for the treatment of
      cancer. Therefore, the development of efficient vector systems is of crucial
      importance in this field. Different adeno-associated virus (AAV) serotypes have
      been characterized so far, which show considerable differences in tissue tropism.
      Consequently, we aimed to characterize the most efficient serotype for this
      application. METHODS: To exclude all influences other than those provided by the
      capsid, all serotypes contained the same transgene cassette flanked by the AAV2
      inverted terminal repeats. We systematically compared these vectors for
      efficiency in human cancer cell directed gene transfer. In order to identify
      limiting steps, the influence of second-strand synthesis and proteasomal
      degradation of AAV in a poorly transducible cell line were examined. RESULTS:
      AAV2 was the most efficient serotype in all solid tumor cells and primary
      melanoma cells with transduction rates up to 98 +/- 0.3%. Transduction above 70%
      could be reached with serotypes 1 (in cervical and prostate carcinoma) and 3 (in
      cervical, breast, prostate and colon carcinoma) using 1000 genomic particles per
      cell. In the colon carcinoma cell line HT-29 proteasomal degradation limited AAV1
      AAV4-mediated gene transfer. Moreover, inefficient second-strand synthesis
      prevents AAV2-mediated transgene expression in this cell line. CONCLUSIONS:
      Recent advances in AAV-vector technology suggest that AAV-based vectors can be
      used for cancer gene therapy. Our comparative analysis revealed that, although
      AAV2 is the most promising candidate for such an application, serotypes 1 and 3
      are valid alternatives. Furthermore, the use of self-complementary AAV vectors
      and proteasome inhibitors significantly improves cancer cell transduction.

PMID- 15945125
TI  - Holistic hope for patients with AIDS in East Africa.

PMID- 15945126
TI  - Scientific literature online: what this means for CAM research.

PMID- 15945127
TI  - Leadership in emergency medical services.

PMID- 15945128
TI  - Ask the tough questions.

PMID- 15945129
TI  - [A 54-year old man with severe circulatory collapse].
AB  - The frequent use of mechanical circulatory assistive devices in the treatment of
      patients in cardiogenic shock increases the need for advanced air and ground
      transport services. In this article we describe a critically ill patient with
      acute myocardial infarction. He was treated with intraaortic balloon pump at the
      local hospital before transfer to a university hospital by air. Close cooperation
      between the university hospital, the Norwegian Air Ambulance and the Norwegian
      aviation authorities has facilitated this service.

PMID- 15945130
TI  - Activity in human reward-sensitive brain areas is strongly context dependent.
AB  - Functional neuroimaging research in humans has identified a number of brain areas
      that are activated by the delivery of primary and secondary reinforcers. The
      present study investigated how activity in these reward-sensitive regions is
      modulated by the context in which rewards and punishments are experienced.
      Fourteen healthy volunteers were scanned during the performance of a simple
      monetary gambling task that involved a "win" condition (in which the possible
      outcomes were a large monetary gain, a small gain, or no gain of money) and a
      "lose" condition (in which the possible outcomes were a large monetary loss, a
      small loss, or no loss of money). We observed reward-sensitive activity in a
      number of brain areas previously implicated in reward processing, including the
      striatum, prefrontal cortex, posterior cingulate, and inferior parietal lobule.
      Critically, activity in these reward-sensitive areas was highly sensitive to the
      range of possible outcomes from which an outcome was selected. In particular,
      these regions were activated to a comparable degree by the best outcomes in each
      condition-a large gain in the win condition and no loss of money in the lose
      condition-despite the large difference in the objective value of these outcomes.
      In addition, some reward-sensitive brain areas showed a binary instead of graded
      sensitivity to the magnitude of the outcomes from each distribution. These
      results provide important evidence regarding the way in which the brain scales
      the motivational value of events by the context in which these events occur.

PMID- 15945131
TI  - A comparative study of US EPA 1996 and 1999 emission inventories in the west Gulf
      of Mexico coast region, USA.
AB  - Emission inventory is one of the required inputs to air quality models. To assist
      in the urban and regional modeling efforts, United States Environmental
      Protection Agency (EPA) has compiled a National Emission Inventory (NEI) for
      criterion pollutants, and the precursors of ozone and particulate matter (PM). In
      December 2002, EPA released the 1999 NEI estimates (NEI99), which represent the
      most recent national emission data. However, the data sets are not in model-ready
      format for air quality simulations. This present work converts the NEI99 Final
      Version 2 data sets into Inventory Data Analyzer (IDA) format and processes the
      data using the Sparse Matrix Operator Kernel Emissions (SMOKE) modeling system to
      generate a gridded emission inventory in a domain covering the west Gulf Coast
      Region, USA. The spatial and diurnal emission characteristics of the gridded
      emission inventories are then assessed and compared with those of the National
      Emission Trend 1996 (NET96). The NEI99 database contains more complete emission
      records in both area and point sources. It is also found that NEI99 data exhibit
      greater emissions with respect to point and mobile sources but smaller emissions
      with respect to area sources when compared to the corresponding gridded NET96
      data in the same study domain. The most distinct differences between the NEI99
      and NET96 databases are CO emission of mobile sources, SO2 emissions of point
      sources, and VOC/PM/NH3/NOx emissions of area and non-road sources. The gridded
      NEI99 data show low VOC/NOx ratios (<2-5) in the urban areas of the study domain.

PMID- 15945132
TI  - Constitutive IL-8 expression in cancer cells is associated with mutation of p53.
AB  - We previously reported that most cancer cell lines constitutively express various
      cytokines including IL-8. But how IL-8 gene expression is regulated in cancer
      cells is still unclear. p53 tumor suppressor gene plays an important role in the
      regulation of transcription and is mutated in cancer cell lines. We investigated
      whether p53 status affects the constitutive expression of IL-8 in human cancer
      cells. SUIT-2 and RERF-LCOK cancer cells constitutively produced high levels of
      IL-8 in culture medium. Both cell lines were shown to carry a p53 mutation, and
      constitutive NF-kappaB transcriptional activity. To analyze whether p53 status
      mediates IL-8 expression, the effect of wild-type p53 (wt-p53) gene transfer on
      activation of NF-kappaB was determined in both cell lines. ELISA showed that the
      IL-8 concentration in medium decreased dose dependently by transient expression
      of wt-p53. Western-blot analysis showed no marked change in NF-kappaB protein
      levels in cell nuclei. EMSA showed no repression of NF-kappaB binding activity
      after transient expression of wt-p53. In contrast, luciferase reporter studies
      indicated that transcriptional activity of NF-kappaB is suppressed by
      transfection of wt-p53. These results show that wt-p53 gene transfer inhibits IL
      8 production and NF-kappaB transcription activity in cancer cells and suggest
      that constitutive IL-8 production in cancer cells is associated with mutation of
      p53.

PMID- 15945133
TI  - Comparing the spatial-frequency response of first-order and second-order lateral
      visual interactions: grating induction and contrast-contrast.
AB  - The magnitudes of two suprathreshold lateral spatial-interaction effects--grating
      induction and contrast--contrast--were compared with regard to their dependence
      upon inducing-grating spatial frequency. Both effects cause the contrast of
      target stimuli embedded in surrounding patterns to be matched nonveridically. The
      magnitudes of each effect were measured in a common unit that indexed the degree
      of nonveridical contrast matching across a large range of target-grating
      contrasts (+/- 0.80). Grating induction was a low-pass effect with respect to
      spatial frequency, whereas contrast-contrast was bandpass, peaking at
      approximately 4.0 cycles deg(-1). The magnitude of grating induction exceeded
      that of contrast--contrast, both overall and at their optimal frequencies
      (0.03125 and 4.0 cycles deg(-1), respectively); the two effects are equipotent at
      an inducing-grating spatial frequency of 1.0 cycle deg(-1). A significant
      negative correlation between the magnitudes of the two effects suggests a link
      whereby activation of second-order normalization mechanisms may inhibit first
      order mechanisms.

PMID- 15945134
TI  - Illustration motifs for effective medical volume illustration.

PMID- 15945135
TI  - Does alpha-linolenic acid intake reduce the risk of coronary heart disease? A
      review of the evidence.
AB  - Alpha-linolenic acid (ALA) is an n-3 polyunsaturated fatty acid found mainly in
      plant sources, including flaxseed oil, canola oil, and walnuts. Although
      substantial evidence indicates that consumption of long-chain n-3 polyunsaturated
      fatty acids from seafood reduces the risk of coronary heart disease (CHD), the
      effect of ALA intake on CHD risk is less well-established. ALA may reduce
      cardiovascular risk through a variety of biologic mechanisms, including platelet
      function, inflammation, endothelial cell function, arterial compliance, and
      arrhythmia. Although clinical benefits have not been seen consistently in all
      studies, most prospective observational studies suggest that ALA intake reduces
      the incidence of CHD, and two randomized trials have demonstrated that a dietary
      pattern that includes fruits, vegetables, whole grains, nuts or legumes, and ALA
      rich foods substantially reduces the recurrence of CHD events. Additional
      observational and clinical studies will help establish the effects of ALA on CHD
      risk and determine whether such effects vary based on gender, duration of intake,
      background dietary intake of seafood, or other factors. Presently, the weight of
      the evidence favors recommendations for modest dietary consumption of ALA (2 to 3
      g per day) for the primary and secondary prevention of CHD.

PMID- 15945136
TI  - Patterns of dietary supplement usage in demographically diverse older people.
AB  - OBJECTIVE: To analyze dietary supplement usage data from 494 older adults, aged
      65 to 101 years. SETTING: Community dwellers living independently of
      institutionalized care. DESIGN: All dietary supplements, including botanicals,
      were recorded to aid in assessing the health status of older adults.
      PARTICIPANTS: 1) 224 individuals enrolled in a study that follows the health of
      persons 85 years and older (oldest-old) in Klamath County, a non-metropolitan
      area in southern Oregon; 2) 134 participants of oldest-old age living in the
      metropolitan Portland area, enrolled in a randomized clinical trial of GBE biloba
      extract (GBE) for dementia prevention; and 3) 136 participants, ages 65-85 years
      (young-old), also of the Portland area, enrolled in a study of the effects of
      yoga and exercise on cognition. MEASUREMENTS: Data verified from labels, not from
      self-report. RESULTS: Of the participants, 70.6% used dietary supplements. Women
      took supplements more often than men, and usage decreased with age. A greater
      percentage, 67.4%, of the non-metropolitan oldest-old took supplements, compared
      to 56.7% of the metropolitan oldest-old. The greatest usage, 89.7%, was in the
      metropolitan young-olds. All of these percentages exceed those for comparable age
      groups in national representative surveys. CONCLUSIONS: Dietary supplement usage
      by older adults in these studies in Oregon exceeded that in other reports and may
      reflect high interest in complementary and alternative medicine. This report
      confirms the results of other studies showing that elderly adults, particularly
      women, use dietary supplements more than other segments of the US population.
      Researchers and clinicians should be aware of this pattern and potential
      conflicts with research design or treatment regimen intended for older people.

PMID- 15945137
TI  - Predicting participation and outcomes in out-of-school activities: similarities
      and differences across social ecologies.
AB  - The majority of research on out-of-school-time activity participation has focused
      on its relation to academic and social development, presumed to be consequences
      of participation, rather than on antecedents or predictors of participation.
      Understanding who participates in these programs can assist program directors in
      improving and sustaining youth involvement. This chapter uses data from two
      research study samples to examine differences in children's activity
      participation based on family social ecology and child gender and how the
      relations between participation and outcomes vary based on sample, gender, and
      activity type. Although children in both samples were of roughly the same age and
      were assessed for similar outcomes, their family incomes, socioeconomic status,
      ethnicity, and neighborhoods were very different. Findings suggest that
      participation in activities varies depending on the young person's social
      ecology, age, and gender. Furthermore, participation in activities was typically
      associated with positive youth outcomes, but these relations varied depending on
      the level of youth participation, type of activity, and social ecology.

PMID- 15945138
TI  - Methodologic factors affect the measurement of anti-basal ganglia antibodies.
AB  - An autoimmune etiology has been proposed for a variety of movement disorders,
      making the detection of autoantibodies a high investigative priority. Recognizing
      the existence of different methodologic approaches to identify these antibodies,
      we sought to investigate the effects of tissue preparation, antibody selection,
      and Western immunoblot detection methods on outcome. ELISA and immunoblotting
      studies were performed in healthy controls evaluating non-pathogenic
      autoantibodies. Our results indicate that enhanced data can be obtained by using
      fresh, rather than frozen, postmortem tissue homogenates for Western immunoblots
      and enzyme-linked immunosorbent assays and support the use of
      electrochemiluminescent detection for Western immunoblots. Molecular localization
      is significantly affected by the selected standard. Removal of lipids from
      homogenates does not affect anti-basal ganglia antibody (ABGA) results.
      Methodological variables should be taken into consideration when performing and
      interpreting neuroimmunological assays using sera or isolated IgG.

PMID- 15945139
TI  - Polarization degree of optical waves with non-Gaussian probability density
      functions: Kullback relative entropy-based approach.
AB  - The definition of degree of polarization for non-Gaussian partially polarized
      light is analyzed. A general framework based on the Kullback relative entropy is
      developed, and properties that enlighten the physical meaning of the degree of
      polarization are established. In particular, it is shown how the degree of
      polarization is related to the measure of proximity between probability density
      functions and to the measure of disorder provided by the Shannon entropy.

PMID- 15945140
TI  - Ball lens coupled fiber-optic probe for depth-resolved spectroscopy of epithelial
      tissue.
AB  - A ball lens coupled fiber-optic probe design is described for depth-resolved
      measurements of the fluorescence and reflectance properties of epithelial tissue.
      A reflectance target, fluorescence targets, and a two-layer tissue phantom
      consisting of fluorescent microspheres suspended in collagen are used to
      characterize the performance of the probe. Localization of the signal to within
      300 microm of the probe tip is observed by use of reflectance and fluorescence
      targets in air. Differential enhancement of the fluorescence signal from the top
      layer of the two-layer tissue phantom is observed.

PMID- 15945141
TI  - Spectral-domain phase microscopy.
AB  - Broadband interferometry is an attractive technique for the detection of cellular
      motions because it provides depth-resolved phase information via coherence
      gating. We present a phase-sensitive technique called spectral-domain phase
      microscopy (SDPM). SDPM is a functional extension of spectral-domain optical
      coherence tomography that allows for the detection of nanometer-scale motions in
      living cells. The sensitivity of the technique is demonstrated, and its
      calibration is verified. A shot-noise limit to the displacement sensitivity of
      this technique is derived. Measurement of cellular dynamics was performed on
      spontaneously beating cardiomyocytes isolated from chick embryos.

PMID- 15945142
TI  - Hilbert phase microscopy for investigating fast dynamics in transparent systems.
AB  - We introduce Hilbert phase microscopy (HPM) as a novel optical technique for
      measuring high transverse resolution quantitative phase images associated with
      optically transparent objects. Because of its single-shot nature, HPM is suitable
      for investigating rapid phenomena that take place in transparent structures such
      as biological cells. The potential of this technique for studying biological
      systems is demonstrated with measurements of red blood cells, and its ability to
      quantify dynamic processes on a millisecond scale is exemplified with
      measurements of evaporating micrometer-sized water droplets.

PMID- 15945143
TI  - Ultrahigh-resolution optical coherence tomography with a fiber laser source at 1
      microm.
AB  - We report a compact, high-power, fiber-based source for ultrahigh-resolution
      optical coherence tomography (OCT) near 1 microm. The practical source is based
      on a short-pulse, ytterbium-doped fiber laser and on generation of a continuum
      spectrum in a photonic crystal fiber. The broadband emission has an average power
      of 140 mW and offers an axial resolution of 2.1 microm in air (<1.6 microm in
      biological tissue). The generation of a broad bandwidth is robust and efficient.
      We demonstrate ultrahigh-resolution, time-domain OCT imaging of in vitro and in
      vivo biological tissues.

PMID- 15945144
TI  - Mid-infrared electric field characterization using a visible charge-coupled
      device-based spectrometer.
AB  - We characterize ultrashort mid-infrared pulses through upconversion by using the
      stretched pulses obtained from the uncompressed output of a chirped-pulse
      amplifier. The power spectrum thus translated into the visible region can be
      readily measured with a standard silicon CCD camera-based spectrometer. The
      spectral phase is also characterized by a variant of zero-added-phase spectral
      phase interferometry for direct electric field reconstruction. This is a general
      method that provides a multiplex advantage over conventional infrared detector
      array-based methods.

PMID- 15945145
TI  - Design and performance of thin cylindrical diffusers created in Ge-doped
      multimode optical fibers.
AB  - Cylindrical fiber diffusers have become common tools for various medical
      therapies. However, their large outer diameters and short lengths restrict their
      clinical application in some newly developed light therapies. Here, a 250-microm
      outer-diameter diffuser with an active length that exceeds 5 cm is presented.
      Diffusers are created in photosensitive optical fibers with outer cladding
      diameters of 140 microm by use of a structured beam from an excimer laser.
      Predetermined emission profiles can be achieved. Photometric characteristics,
      including longitudinal, polar, and azimuthal emission diagrams, were determined
      by use of a goniometer to assess the light-emission performance of the diffuser.
      Longitudinal isotropy of better than +/- 10% was achieved. Polar and azimuthal
      emissions were within +/- 15% of those of an ideal linear Lambertian emitter.
      Polar uniformity could be improved by an insignificant increase in the outer
      diameter by use of a diffusing recoating compound. The residual leakage of light
      at the distal end of the diffuser can be as little as 1%. Other physical
      parameters tested include minimal bending radius after recoating (< 5 mm) and
      maximum power handling (> 1.0W cm(-1)). All materials employed were
      biocompatible.

PMID- 15945146
TI  - Radon transform orientation estimation for rotation invariant texture analysis.
AB  - This paper presents a new approach to rotation invariant texture classification.
      The proposed approach benefits from the fact that most of the texture patterns
      either have directionality (anisotropic textures) or are not with a specific
      direction (isotropic textures). The wavelet energy features of the directional
      textures change significantly when the image is rotated. However, for the
      isotropic images, the wavelet features are not sensitive to rotation. Therefore,
      for the directional textures, it is essential to calculate the wavelet features
      along a specific direction. In the proposed approach, the Radon transform is
      first employed to detect the principal direction of the texture. Then, the
      texture is rotated to place its principal direction at 0 degrees. A wavelet
      transform is applied to the rotated image to extract texture features. This
      approach provides a features space with small intraclass variability and,
      therefore, good separation between different classes. The performance of the
      method is evaluated using three texture sets. Experimental results show the
      superiority of the proposed approach compared with some existing methods.

PMID- 15945147
TI  - [Interdisciplinary S2 guidelines. Diagnosis and therapy in bone and deep venous
      thrombosis and pulmonary embolism].

PMID- 15945148
TI  - Oasis of fun at Mount Desert Island.

PMID- 15945149
TI  - Linear technique of laparoscopic Roux-en-Y gastric bypass.
AB  - The laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the most common
      procedure performed for treatment of morbid obesity in the United States. The
      technique reported in this chapter requires mastering of extra-corporeal and
      intra-corporeal laparoscopic suturing, but is safe, cost effective, and
      technically feasible. Use of the straight needle eliminates the challenge of
      proper needle orientation encountered with a curved needle. The linear technique
      is used to construct the gastrojejunostomy because it is time saving and
      relatively simple. An endoscopic ruler and bougie are used to ensure a consistent
      pouch size and alimentary limb length. This chaper demonstrates the use of
      preoperative preparation, and a meticulous surgical technique using the linear
      stapler, to perform a combined total of more than 1800 cases.

PMID- 15945150
TI  - Beverages: bottled water. Final rule.
AB  - The Food and Drug Administration (FDA) is amending its bottled water quality
      standard regulations by revising the existing allowable level for the contaminant
      arsenic. As a consequence, bottled water manufacturers are required to monitor
      their finished bottled water products for arsenic at least once each year under
      the current good manufacturing practice (CGMP) regulations for bottled water.
      Bottled water manufacturers are also required to monitor their source water for
      arsenic as often as necessary, but at least once every year unless they meet the
      criteria for the source water monitoring exemptions under the CGMP regulations.
      This final rule will ensure that the minimum quality of bottled water, as
      affected by arsenic, remains comparable with the quality of public drinking water
      that meets the Environmental Protection Agency's (EPA's) standards.

PMID- 15945151
TI  - Human embryonic stem cell research: why the discarded-created-distinction cannot
      be based on the potentiality argument.
AB  - Discussions about the use and derivation of pluripotent human embryonic stem
      cells are a stumbling block in developing public policy on stem cell research. On
      the one hand there is a broad consensus on the benefits of these cells for
      science and biomedicine; on the other hand there is the controversial issue of
      killing human embryos. I will focus on the compromise position that accepts
      research on spare embryos, but not on research embryos ('discarded-created
      distinction', from now on d-c-d). I will point out that this viewpoint is hard to
      maintain. The main focus is that the 'revealed beliefs' of its defenders are
      inconsistent with their 'professed beliefs', more specifically with their main
      argument, i.e. the potentiality argument. I will point out that (1) the defenders
      of d-c-d actually grant a relative moral status to the human embryo, (2) this
      moral status is dependent on internal and external criteria of potentiality, (3)
      potentiality seen as a variable value that also depends on external criteria
      cannot justify d-c-d, and (4) an approach to human embryonic stem cell-research
      that would also allow the use of research embryos is more compatible with the
      feelings, attitudes and values of those who currently defend d-c-d and,
      therefore, could lead to a broader consensus and to actions that alleviate
      individual human suffering.

PMID- 15945152
TI  - [Proceedings of the 3rd Conference on Prevention in Nephrology and Dialysis.
      Mantova, Italy, 8-9 May 2004].

PMID- 15945153
TI  - Lung cancer: multidisciplinary refresher course for residents. Rome, Italy,
      October 1-2, 2004.

PMID- 15945154
TI  - [Motivation or doomed venture? Concept and 1-year evaluation of a forensic
      admission-, diagnostics- and motivation ward for addicts].

PMID- 15945155
TI  - [Delinquent analysis and delinquent processing in prison treatment].

PMID- 15945156
TI  - [Extinction and conservation: role of models in studying and teaching biologic
      diversity].

PMID- 15945157
TI  - Suggested guidelines for the practice of arthroscopic surgery.

PMID- 15945158
TI  - More than 2.9 million Californians now food insecure--one in three low-income, an
      increase in just two years.

PMID- 15945159
TI  - The determination of 'best interests' in relation to childhood vaccinations.
AB  - There are many different ethical arguments that might be advanced for and against
      childhood vaccinations. In this paper I will explore one particular argument that
      focuses on the idea that childhood vaccinations are justifiable because they are
      held to be in the best interests of a particular child. Two issues arise from
      this idea. The first issue is how best interests are to be determined in the case
      of childhood vaccinations. The second issue is what follows from this to justify
      potential interventions within the family in relation to such vaccinations. I
      argue that best interests must be characterised objectively in such situations
      and that this means that, in at least some cases, parental decision-making about
      vaccinating their children may be overridden.

PMID- 15945160
TI  - The bioethics of care: widows, monastics, and a Christian presence in health
      care.
AB  - At the beginning of the twenty-first century, with vocations to the Christian
      religious orders of the West in marked decline, an authentic Christian presence
      in health care is threatened. There are no longer large numbers of women willing
      to offer their life labors bound in vows of poverty, chastity, and obedience, so
      as to provide a real preferential option for the poor through supporting an
      authentic Christian mission in health care. At the same time, the frequent
      earlier death of men leaves a large number of widows, some in need of care and
      some able to provide care. Drawing on the role of widows sketched in 1 Timothy 2,
      one can envision Christian widows entering a life of prayer and service in health
      care settings. As female monastics, such widows could reintroduce a salient
      Christian presence in health care. How one ties this response to the message of 1
      Timothy 2 will depend on one's understanding of the status of Scripture, the
      significance of tradition, the nature of theological epistemology, the meaning of
      theology, the nature of the Church, and the ontology of gender. The position
      taken on these issues will define the character of a Christian bioethics of care.

PMID- 15945161
TI  - The Order of Widows: what the early church can teach us about older women and
      health care.
AB  - This article argues that the early Christian "order of widows" provides a
      fruitful model for Christian ethicists struggling to address the medical and
      social problems of elderly women today. After outlining the precarious state of
      the "almanah"--or widow--in biblical times, it describes the emergence of the
      order of widows in the early Church. Turning to the contemporary situation, it
      argues that demographics both in the United States and around the globe suggest
      that meeting the needs of elderly women will become an enormous challenge in the
      years to come. The order of widows illustrates a three-fold conception of
      solidarity that has immediate implications today. That conception of solidarity
      encourages us: 1) to identify the unique medical needs of elderly women (e.g.,
      osteoporosis); 2) to find ways of overcoming their societal isolation, which can
      increase their risk of medical and psychological problems; and 3) to develop
      strategies for enabling them to remain contributing members of the community for
      as long as possible.

PMID- 15945162
TI  - Ruth's resolve: what Jesus' great-grandmother may teach about bioethics and care.
AB  - When thinking about the intersection of care and Christian bioethics, it is
      helpful to follow closely the account of Ruth, who turned away from security and
      walked alongside her grieving mother-in-law to Bethlehem. Remembering Ruth may
      help one to heed Professor Kaveny's summoning of Christians to remember "the
      Order of Widows" and the church's historic calling to bring "the almanah into its
      center rather than pushing her to its margins." Disabled, elderly and terminally
      ill people often seem, at least implicitly, expendable. By hearing the scriptural
      account of Jesus' steadfast great-grandmother, readers may recall another way.
      One may read Ruth's care for Naomi as a performative, prophetic act of faith.
      Ruth's faithful resolve, when set next to Orpah's prudent way, challenges the
      notion that a bioethic of care is innately feminine, and may further call women
      and men corporately to participate in a kind of care that is strenuous work.

PMID- 15945163
TI  - Practicing the Order of Widows: a new call for an old vocation.
AB  - This essay argues for a renewed institution of an ancient Christian practice, the
      Order of Widows. Drawing on the Roman Catholic tradition's recent writings on the
      elderly, particularly the 1998 document from the Pontifical Council for the Laity
      entitled "The Dignity of Older People and their Mission in the Church and in the
      World," I argue that we find within the Roman Catholic tradition advocacy for a
      renewed understanding of the vocation of the elderly within the Church. Building
      on this, I then trace in the broadest of outlines some elements of what a renewal
      of the Order of Widows might look like. In doing so, it becomes clear how this
      new ecclesial practice addresses health issues of older women (devaluation,
      marginalization, loss of voice, impoverishment, debilitation, loneliness,
      isolation, and euthanasia). More importantly, such a practice moves beyond
      principles to demonstrate a concrete alternative. As such it would provide a
      powerful witness to the very culture the Church seeks to transform.

PMID- 15945164
TI  - Contemporary ethics from an ambiguous past.
AB  - Kaveny recommends models drawn from the Gospel of John and the practices of the
      early church for modern Christians in their response to older women and their
      health needs. She draws upon a historical reconstruction of the early Christian
      Order of Widows to propose a normative standard of care for elderly women, one
      that attends seriously to their bodily needs but also to their needs for
      inclusion and engagement in the social and vocational world both as givers and
      recipients of care. This is also to serve as an overarching model for a bioethics
      that prizes the embodied existence of all women and rejects judgments of
      appropriate treatment based on their social utility. The following response
      raises questions about the exegetical and historical foundations of Kaveny's
      analysis. However, these caveats may not detract substantially from the normative
      usefulness of her work.

PMID- 15945165
TI  - Profile of drug-resistant case in New York.

PMID- 15945166
TI  - Transplant study needs patients.

PMID- 15945167
TI  - From advanced imaging. When epidural fat is more than just epidural fat.

PMID- 15945168
TI  - From advanced imaging. When a novel construct meets a challenge.

PMID- 15945169
TI  - Prospective study among cutaneous leishmaniasis cases in Tripoli Central
      Hospital, Tripoli, Libya.
AB  - One hundred and nine cases of cutaneous leishmaniasis were referred to
      Dermatology unit, Tripoli Central Hospital from 24 localities in north-west Libya
      during the period from September to December 1994. Clinically most of the lesions
      were multiple and distributed on the uncovered parts of the body, and the size
      ranged from 1 to 5 cm. In diameter. The prevalence of infection was 65.3% among
      age groups 1-30 year old. Patients responded well to the treatment with sodium
      stibagluconate.

PMID- 15945170
TI  - Contribution of DFNB1 and DFNB2 loci to neurosensory deafness in affected
      Tunisian families.
AB  - Classical studies have demonstrated genetic heterogeneity for nonsyndromic
      autosomal recessive congenital neurosensory deafness. The first two DFNB1 and
      DFNB2 locations were found using two consanguineous Tunisian families
      respectively from north and south. We tested these loci for cosegregation with
      deafness in twenty four southern families with nonsyndromic presumed congenital
      sensorineural deafness and a pedigree structure consistent with autosomal
      recessive inheritance. Only in our families, did deafness cosegregate with DFNB1.
      Although our families are from the south, none of them showed linkage to DFNB2.

PMID- 15945172
TI  - [Clinical pathology laboratory].

PMID- 15945171
TI  - [The anti-platelet aggregation drugs: new approaches based on snake venom
      polypeptides].

PMID- 15945173
TI  - [Clinical bacteriology laboratory].

PMID- 15945174
TI  - [Mycobacterial laboratory].

PMID- 15945175
TI  - [Enterobacterial bacteriology of water and food product laboratory].

PMID- 15945176
TI  - [Veterinary science laboratory].

PMID- 15945177
TI  - [Clinical virology laboratory].

PMID- 15945178
TI  - [Rabies laboratory].

PMID- 15945179
TI  - [Immunology laboratory].

PMID- 15945180
TI  - [Hematology laboratory].

PMID- 15945181
TI  - [Radioimmunology laboratory].

PMID- 15945182
TI  - [Parasitic epidemiology and ecology laboratory].

PMID- 15945183
TI  - [Clinical parasitology laboratory].

PMID- 15945184
TI  - [Medical entomology laboratory].

PMID- 15945185
TI  - [Venoms and toxins laboratory].

PMID- 15945186
TI  - [Clinical biochemistry laboratory].

PMID- 15945187
TI  - [BCG production laboratory].

PMID- 15945188
TI  - [Virus production laboratory].

PMID- 15945189
TI  - [Production unit for veterinary vaccines].

PMID- 15945190
TI  - [Immunotechnology and production of biological materials laboratory].

PMID- 15945191
TI  - [Culture media production laboratories].

PMID- 15945192
TI  - [Therapeutic serum purification laboratory].

PMID- 15945193
TI  - [Laboratory for the control of serum vaccines and other biological products].

PMID- 15945194
TI  - [Conditioning and stocking laboratory].

PMID- 15945195
TI  - [Animal units].

PMID- 15945196
TI  - [Experimental animal science units of Soukra].

PMID- 15945197
TI  - [Antirabies and international vaccination unit].

PMID- 15945198
TI  - [Sales of serums, vaccines and other biological products unit].

PMID- 15945199
TI  - [Library].

PMID- 15945201
TI  - A model of exact small-number representation.
AB  - To account for the size effect in numerical comparison, three assumptions about
      the internal structure of the mental number line (e.g., Dehaene, 1992) have been
      proposed. These are magnitude coding (e.g., Zorzi & Butterworth, 1999),
      compressed scaling (e.g., Dehaene, 1992), and increasing variability (e.g.,
      Gallistel & Gelman, 1992). However, there are other tasks besides numerical
      comparison for which there is clear evidence that the mental number line is
      accessed, and no size effect has been observed in these tasks. This is contrary
      to the predictions of these three assumptions. Moreover, all three assumptions
      have difficulties explaining certain symmetries in priming studies of number
      naming and parity judgment. We propose a neural network model that avoids these
      three assumptions but, instead, uses place coding, linear scaling, and constant
      variability on the mental number line. We train the model on naming, parity
      judgment, and comparison and show that the size effect appears in comparison, but
      not in naming or parity judgment. Moreover, no asymmetries appear in primed
      naming or primed parity judgment with this model, in line with empirical data.
      Implications of our findings are discussed.

PMID- 15945202
TI  - Acquired distinctiveness and equivalence in human discrimination learning:
      evidence for an attentional process.
AB  - In a first stage of training, participants learned to associate four visual cues
      (two different colors and two different shapes) with verbal labels. For Group S,
      one label was applied to both colors and another to both shapes; for Group D, one
      label was applied to one color and one shape, and the other label to the other
      cues. When subsequently required to learn a task in which a given motor response
      was required to one of the colors and one of the shapes, and a different response
      to the other color and the other shape, Group D learned more readily than Group
      S. The task was designed so that the associations formed during the first stage
      of training could not generate differential transfer to the second stage. The
      results are consistent, however, with the proposal that training in which similar
      cues are followed by different outcomes will engage a learning process that
      boosts the attention paid to features that distinguish these cues.

PMID- 15945200
TI  - Is there a geometric module for spatial orientation? Squaring theory and
      evidence.
AB  - There is evidence, beginning with Cheng (1986), that mobile animals may use the
      geometry of surrounding areas to reorient following disorientation. Gallistel
      (1990) proposed that geometry is used to compute the major or minor axes of space
      and suggested that such information might form an encapsulated cognitive module.
      Research reviewed here, conducted on a wide variety of species since the initial
      discovery of the use of geometry and the formulation of the modularity claim, has
      supported some aspects of the approach, while casting doubt on others. Three
      possible processing models are presented that vary in the way in which (and the
      extent to which) they instantiate the modularity claim. The extant data do not
      permit us to discriminate among them. We propose a modified concept of modularity
      for which an empirical program of research is more tractable.

PMID- 15945203
TI  - Sequential task predictability in task switching.
AB  - Many studies of task switching have found that a prolonged preparation time
      reduces switch costs. An alternative manipulation of task preparation is based on
      sequential task predictability, rather than preparation time. In Experiments 1
      and 2 of the present study, participants performed explicitly instructed task
      sequences (i.e., AABB) and were then transferred to a random sequence. The
      observed benefit of predictability-based task preparation was not switch
      specific. In Experiment 3, the participants changed from random to predictable
      tasks. The observed predictability benefit again was not switch specific. The
      data thus suggest that task switching does not necessarily require a switch
      specific reconfiguration process. Rather, task-specific control processes may be
      needed in both task switches and repetitions.

PMID- 15945204
TI  - Contextual control over lexical and sublexical routines when reading english
      aloud.
AB  - Are the processes responsible for reading aloud single well-formed letter strings
      under contextual control? Despite the widespread contention that the answer to
      this question is "yes," it has been remarkably difficult to provide a compelling
      demonstration to that effect. In a speeded naming experiment, skilled readers
      read aloud exception words (such as PINT) that are atypical in terms of their
      spelling sound correspondences and nonwords (such as FLAD) that appeared in a
      predictable sequence. Subjects took longer to name both words and nonwords when
      the item on the preceding trial was from the other lexical category, relative to
      when the preceding item was from the same lexical category. This finding is
      consistent with the relative contributions of lexical and sublexical knowledge
      being controlled. We note a number of different ways that this control could
      arise and suggest some directions for future research.

PMID- 15945205
TI  - Basic processes in reading: is visual word recognition obligatory?
AB  - Visual word recognition is commonly argued to be automatic in the sense that it
      is obligatory and ballistic. The present experiments combined Stroop and visual
      search paradigms to provide a novel test of this claim. An array of three, five,
      or seven words including one colored target (a word in Experiments 1 and 2, a bar
      in Experiment 3) was presented to participants. An irrelevant color word also
      appeared in the display and was either integrated with or separated from the
      colored target. The participants classified the color of the single colored item
      in Experiments 1 and 3 and determined whether a target color was present or
      absent in Experiment 2. A Stroop effect was observed in Experiment 1 when the
      color word and the color target were integral, but not when the color word and
      the color target were separated. No Stroop effect was observed in Experiment 2.
      Visual word recognition is contingent on both the distribution of spatial
      attention and task demands.

PMID- 15945206
TI  - Fixation durations before word skipping in reading.
AB  - We resolve a controversy about reading fixations before word-skipping saccades
      which were reported as longer or shorter than control fixations in earlier
      studies. Our statistics are based on resampling of matched sets of fixations
      before skipped and nonskipped words, drawn from a database of 121,321 single
      fixations contributed by 230 readers of the Potsdam sentence corpus. Matched
      fixations originated from single-fixation forward-reading patterns and were
      equated for their positions within words. Fixations before skipped words were
      shorter before short or high-frequency words and longer before long or low
      frequency words in comparison with control fixations. Reasons for inconsistencies
      in past research and implications for computational models are discussed.

PMID- 15945207
TI  - Diminutives in child-directed speech supplement metric with distributional word
      segmentation cues.
AB  - In two experiments, we explored whether diminutives (e.g., birdie, Patty,
      bootie), which are characteristic of child-directed speech in many languages, aid
      word segmentation by regularizing stress patterns and word endings. In an
      implicit learning task, adult native speakers of English were exposed to a
      continuous stream of synthesized Dutch nonsense input comprising 300 randomized
      repetitions of six bisyllabic target nonwords. After exposure, the participants
      were given a forced choice recognition test to judge which strings had been
      present in the input. Experiment 1 demonstrated that English speakers used
      trochaic stress to isolate strings, despite being unfamiliar with Dutch
      phonotactics. Experiment 2 showed benefits from invariance introduced by
      affricates, which are typically found at onsets of final syllables in Dutch
      diminutives. Together, the results demonstrate that diminutives contain prosodic
      and distributional features that are beneficial for word segmentation.

PMID- 15945208
TI  - Pauses and durations exhibit a serial position effect.
AB  - This article reports evidence of two kinds of serial position effects in
      immediate serial recall: One involves interresponse pauses, and the other
      response durations. In forward and backward recall, responding was faster at
      initial and final positions than at center positions, exhibitinga bow-shaped
      function relative to serial position. These data were obtained in a spoken recall
      study in which ungrouped lists of four to six words and postcuing of recall
      direction were used. The pause pattern is consistent with several models of
      serial memory, including a distinctiveness model (Brown, Neath, & Chater, 2002)
      and a version of the ACT-R model augmented with a spontaneous grouping strategy
      (Maybery, Parmentier, & Jones, 2002). The duration pattern suggests that response
      articulation depends on the processing context, rather than being modular.

PMID- 15945209
TI  - What makes working memory spans so predictive of high-level cognition?
AB  - Working memory (WM) span tasks involving a complex activity performed
      concurrently with item retention have proven to be good predictors of high-level
      cognitive performance. The present study demonstrates that replacing these
      complex self-paced activities with simpler but computer-paced processes, such as
      reading successive letters, yields more predictive WM span measures. This finding
      suggests that WM span tasks evaluate a fundamental capacity that underpins
      complex as well as elementary cognitive processes. Moreover, the higher
      predictive power of computer-paced WM span tasks suggests that strategic factors
      do not contribute to the relationship between WM spans and high-level cognition.

PMID- 15945210
TI  - Semantic similarity and immediate serial recall: is there an effect on all
      trials?
AB  - In immediate serial recall, items are better recalled when they are all drawn
      from the same semantic category. This is usually accounted for by a two-stage
      retrieval-based framework, in which, at recall, long-term knowledge is used to
      reconstruct degraded phonological traces. The category shared by list items would
      serve as an additional retrieval cue restricting the number of recall candidates.
      Usually, the long-term search set is not defined, but some authors have suggested
      an extended search set and others a restricted set that is composed of the most
      recently presented items. This was tested in an experiment in which participants
      undertook an immediate serial recall task either alone or under articulatory
      suppression with either semantically similar or dissimilar lists. A trial-by
      trial analysis revealed that, in both quiet and suppression conditions, items
      from similar lists were better recalled on all the trials, including the first
      one. In addition, there was no interaction between semantic similarity and trial,
      indicating that the effect of similarity was of similar size on all the trials.
      The results are best interpreted within a proposal suggesting an extended long
      term search set.

PMID- 15945211
TI  - The role of local and global properties in comparison of analogical visual
      scenes.
AB  - Love, Rouder, and Wisniewski (1999) obtained interesting results showing that, in
      a same/different task on abstract visual scenes, subjects were able to process
      global properties quickly, even before local properties were identified. Our aim
      in this work is to explore more fully the complex relationships that exist
      between local processing and global processing. In our first experiment, we
      tested the robustness and generality of these global and local effects by using
      another, very different kind of local element. We showed that the global effects
      remain strong even when the local elements are neither conventional nor easily
      discriminable. In the second experiment, we showed that there exists an
      intermediate level of similarity between purely local and purely global
      similarity. Furthermore, we found that even when a stronger form of local
      dissimilarity is manipulated (through the introduction of different local
      elements), global effects were still observed. We conclude with a discussion of
      the respective roles of global and local properties in light of our findings.

PMID- 15945212
TI  - The lengthening effect revisited: a reply to Prinzmetal and Wilson (1997) and
      Masin (1999).
AB  - In the present study, the lengthening phenomenon (Tsal & Shalev, 1996), namely,
      the increase in perceived length of unattended lines, was reexamined in light of
      criticisms by Prinzmetal and Wilson (1997) and Masin (1999). Prinzmetal and
      Wilson suggested that the effect was not due to attentional factors but to the
      spatial interaction between the attended line and the cue used to direct
      attention. We have replicated the lengthening effect when both attended and
      unattended lines are preceded by cues at a nearby location, showing that the
      effect is not caused by spatial cues per se, but instead reflects an inherent
      property of the attentional system. Masin argued that the lengthening effect is
      not robust, because it occurs for some but not for all participants. In the
      present study, the lengthening effect was highly reliable, occurring for each
      participant for a variety of line lengths.

PMID- 15945213
TI  - [Rheumatoid arthritis (RA) and systemic lupus erythematosus(SLE)].

PMID- 15945214
TI  - [Rheumatoid arthritis--clinical picture and important differential diagnoses].
AB  - Rheumatoid Arthritis is a chronic disease of unknown origin. It affects the
      joints, but also virtually every other organ. Its cause remains still unknown.
      The prevalence rate is approximately 1% worldwide, with some racial differences.
      Women are affected three times more often than men. Symmetric swelling of the
      joints and a substantial morning stiffness are the typical signs of the disease.
      Most often the wrists, MCP and PIP joints, and the ankle and MTP joints are
      affected. The arthritis is usually progressive, leading to destructive changes of
      the affected joints. Neurological symptoms can occur following destruction of the
      atlantoaxial joint. Diagnosis and classification of the disease follows the 1987
      revised American Rheumatism Association criteria, but for practical purposes the
      approach described by Visser et al. seems more useful, calculating odds ratios
      for persisting and erosive disease. Effective treatment can start earlier with
      this approach. Conventional radiology and serum markers, especially the newer
      antibodies against CCP are important aids in diagnosing rheumatoid arthritis.
      Diseases to be separated from rheumatoid are other arthritides of autoimmune
      origin, the cristal arthropathies, vasculitides, septic and parainfectious
      arthritides, osteoarthritis, and paraneoplastic syndromes.

PMID- 15945215
TI  - [Rheumatoid arthritis--pearls and myths].

PMID- 15945216
TI  - [Rheumatoid arthritis--new perspectives in its diagnosis].
AB  - The early diagnosis of rheumatoid arthritis has ever been a challenge. The need
      of an early accurate and sensitive diagnostic have grown even more in the last
      few years since new data showed that an aggressive and early therapy may
      influence the course of RA and even remission may be achieved. Traditional and
      new diagnostic tools like ultrasound and MRI are reviewed and analysed in the
      perspective of early recognition of disease.

PMID- 15945217
TI  - [Management of patients with rheumatoid arthritis].
AB  - Recent years have shown considerable advances in the understanding of
      pathophysiology and clinical course of patients with rheumatoid arthritis. We now
      know that there is preclinical disease. Autoantibodies precede clinical symptoms
      and erosive disease can be seen in patients as early as at the beginning of the
      symptoms. Clinical progress has come from a better recognition of the natural
      history of disease. Outcome measures were developed and validated, allowing
      innovative trial design. Therapy must aim at achieving clinical remission,
      reversal from destructive to nondestructive arthritis and even healing of
      erosions. Such aim necessitates early diagnosis of disease and aggressive
      treatment. Regular assessment of the disease state should be performed. For
      disease assessment validated tools should be used. The search for new therapies
      is ongoing. Studies indicate there is a considerable window of opportunity in
      very early rheumatoid arthritis. If we can use this window of opportunity with an
      efficient therapeutic strategy we should be able to change the course of disease
      or even achieve long term remission.

PMID- 15945218
TI  - [Pathogenesis of systemic lupus erythematosus (SLE)--the central role of
      complement].
AB  - The traditional view of the pathogenesis of SLE is that immune complexes
      containing autoantigens and autoantibodies activate complement, and that this
      causes inflammatory injury to tissues. Although this model is biologically
      plausible, it cannot account for all of the clinical observations that link the
      complement system and SLE. In particular, the observation that complement
      deficiency causes lupus is hard to reconcile with the concept that complement
      activation products are the major cause of inflammatory injury in the disease.
      More recent data suggests that the role of complement in SLE is rather
      protective. Bindung of complement might prevent an autoimmune response by
      supporting the clearance of immuncomplexes and apoptotic cell debrid.

PMID- 15945219
TI  - [Systemic lupus erythematosus--myths and dogma].
AB  - In this short review, four different aspects of SLE are discussed. The ACR
      criteria for SLE were established for the differentiation of SLE from other
      autoimmune diseases and not for the direct diagnosis of SLE. Treatment of SLE is
      continuously re-evaluated thanks ongoing clinical research. Best clinical
      practice should be based on experienced and continuous knowledge in the field
      rather than on dogmatic treatment schemes. SLE is not one disease, but a series
      of clinical pictures associated into a syndrome. Finally, do not forget that
      patients with the SLE syndrome suffer almost always from debilitating fatigue.

PMID- 15945220
TI  - [Systemic lupus erythematosus (SLE)--a brief guide to its diagnosis].
AB  - In this overview, simple clinical elements that, in appropriate combination,
      should raise suspicion of dealing with an SLE-patient are reviewed. Meaningful
      diagnostic steps that should follow the clinical suspicion are described, and
      their respective value in firmly establishing the diagnosis of SLE discussed.

PMID- 15945221
TI  - [Skin manifestations of lupus erythematosus].
AB  - There are multiple forms of cutaneous manifestations of lupus erythematosus. In
      general strictly cutaneous forms are distinguished from systemic lupus
      erythematosus with cutaneous involvement. Systemic lupus erythematosus can be
      regarded either as primarily with skin signs or secundarily after initial
      involvement of the skin. Typical forms of cutaneous lupus erythematosus are the
      subacute cutaneous and the discoid form.

PMID- 15945222
TI  - [Lupus nephritis].
AB  - Lupus nephritis is a serious complication of systemic lupus erythematodes. It is
      important to establish the correct diagnosis in order to initiate the optimal
      treatment for a specific patient. Early therapy will prevent organ damage which
      otherwise can dramatically increase morbidity and mortality. This article
      provides information about pathogenesis, manifestations, laboratory
      investigations, histopathology and treatment of lupus nephritis. Besides the
      indication for treatment the various immunosuppressive protocols are discussed.
      Moreover, a specific treatment option is proposed and the follow up is described.

PMID- 15945223
TI  - What are the barriers to ideal patient care?

PMID- 15945224
TI  - Trapped in health care limbo. Without documentation, a teenager struggles to find
      a new kidney.

PMID- 15945225
TI  - GAKP responds to CMS proposed conditions for coverage.

PMID- 15945226
TI  - Renal technology advancing--but who will pay?

PMID- 15945227
TI  - The information age: are we up to date in ESRD?

PMID- 15945228
TI  - Technology doesn't have to thwart patient autonomy.

PMID- 15945229
TI  - Nurturing 'fistula culture' in a hospital environment.

PMID- 15945230
TI  - Finding a professional advisor for your practice.

PMID- 15945231
TI  - [Public health importance of ischemic heart disease].
AB  - The high cardiovascular morbidity and mortality makes good quality and
      reproducible data essential to obtain adequate conclusion. Data collected in
      order to be well financed are inadequate, special conducted surveys are
      mandatory. Even in absence of such surveys the high prevalence and high mortality
      data are widely accepted. Theoretically the total elimination of risk factors and
      the application of the four preventive drugs would bring very effective (75-90%)
      risk reduction. The excellent perspective dose not support the sparing with
      preventive efforts.

PMID- 15945232
TI  - [Endothelial function and ischemic heart disease].
AB  - The original hypothesis of the development of human atherosclerosis and ischemic
      heart disease called "response-to-injury" suggested the loss of integrity of the
      endothelium as the first step of the process. The recent version of this
      hypothesis emphasizes the term of endothelial dysfunction, that can be triggered
      by any of the well known cardiovascular risk factors. The atherosclerotic
      process, starting with endothelial dysfunction is a slow grade inflammatory
      process, promoting the oxidation of the low density lipoprotein molecules,
      activation of cell adhesion molecules as well as various ligands and cytokines,
      and activating immunological processes resulting in the development of unstable
      atherosclerotic plaque, followed by plaque rupture and formation of
      atherothrombotic lesions. Among the laboratory methods used for the detection of
      endothelial dysfunction, the flow mediated vasodilation (FMD) is increasingly
      known. A novel method is the laser Doppler flowmetry, still adapted to routine
      clinical tests. Clinical experiments are currently running with the
      coronarographic evaluation of intravascular flow velocity (slow coronary flow
      phenomenon), and also with the isolation and clinical evaluation of the
      circulating endothelial cells in patients with ischemic heart disease.

PMID- 15945233
TI  - [Mechanism and drug treatment of atherothrombosis].
AB  - The better understanding of processes and consequences in atherothrombosis has
      changed recent cardiovascular medicine fundamentally. The importance of multiple
      action combined medical drug therapy has been obviously outlined by the discovery
      of the simultaneous, multiplex, multilocular merit of atherothrombosis. Recently,
      the detrimental effect of selective cyclooxygenase-2 inhibitors has been shown on
      vascular integrity. Certain lipid lowering drugs with pleiotropic and lipid
      effects have become a treatment option of the acute phase of atherothrombosis.
      Similarly to statins, combined antiplatelet drug strategy has been proven
      effective in any form of plaque rupture of coronary arteries, with either
      spontaneous or intervention-related origin (every appearance of acute coronary
      syndromes, percutaneous angioplasty). Occlusive forms of atherothrombosis need
      urgent reperfusion/revascularisation technics, as fibrinolytic therapy,
      endovascular or rarely traditional surgery.

PMID- 15945234
TI  - [Present state and perspectives of interventional cardiology].
AB  - The development and the present practice of percutaneous coronary interventions
      are outlined. The author considers the application of coronary stents, which
      prevents the abrupt coronary occlusion during balloon angioplasty and up-to-date
      antiplatelet therapy the basis for the present success and distribution of the
      method. In the years to come the number of interventional laboratories and
      patients treated by percutaneous methods will grow also in Hungary. The
      application of drug eluting stents will be more widespread and also other methods
      of higher safety and efficacy will follow.

PMID- 15945235
TI  - [The importance of the knowledge of acute coronary syndrome].
AB  - The acute coronary syndrome is not only a new phrase in the every day medical
      practice. It has basically changed not only our knowledge but our way of
      thinking. In the background of these changes is the understanding of the common
      origin of the different forms of acute ischemic heart diseases. Although acute
      coronary syndrome is one of the hot topic of today's cardiology and
      interventional cardiology, this review was not made for only interventional
      cardiologist, much rather for real world practitioner to help understanding the
      treatment of acute coronary syndrome, which is one of the real challenge of the
      every day practice.

PMID- 15945236
TI  - [Chronic heart failure--the epidemic of the 21st century].
AB  - Heart failure represents a major public health problem in the industrialized
      countries and despite of optimal medical treatment its mortality remains high.
      The history of its management reflects growth and changes in our understanding of
      its pathophysiology. In the past, pharmacological treatment of heart failure was
      aimed only at relieving edema and improving hemodynamics. Today, however, a major
      aim of treatment is to antagonize the sympathetic nervous system and renin
      angiotensin-aldosterone system, to avert harmful effects of neurohormonal
      activation on the myocardium and peripheral vessels. Currently, the major
      pharmacological treatments for heart failure are diuretics, ACE inhibitors, beta
      blockers and (in NYHA classes III-IV) aldosterone antagonists. Some patients may
      also require specific treatment with additional drugs (e.g. anti-arrhythmia
      agents, anticoagulants, or vasodilators) or procedures such as coronary
      revascularization, or implantable devices such as pacemakers and implantable
      cardioverter defibrillators, or resynchronization devices. Patients with end
      stage heart failure may require cardiac transplantation or ventricular assist
      devices. This review is summarized the recent practical drug therapy of heart
      failure and the results of the newer clinical trial.

PMID- 15945237
TI  - [Latest results of treatment with pacemaker and implantable cardioverter
      defibrillators].
AB  - Device-based anti-arrhythmic therapy is one of the most dynamically evolving
      branches of the medicine. Brady- and tachyarrhythmias can be treated efficiently
      and cost-effective with current pacemakers and ICDs. Beside conventional
      indications new indications have appeared in the last years: resynchronization
      treatment of severe congestive heart failure with biventricular pacing, primary
      prevention of sudden cardiac death with ICD, reduction of intraventricular
      gradient in hypertrophic obstructive cardiomyopathy. Several large clinical
      studies have investigated the efficacy of treatment in conventional indications,
      so the role of pacemaker therapy in carotid sinus hyperaesthesia or sinus node
      disease has been elucidated. Newer studies are trying to clarify the type or
      programming of the pacemaker in a given indication: physiological pacemakers have
      a more beneficial effect on the quality of life and decrease the incidence of
      atrial fibrillation. The implanted devices have frequency adaptation with new
      sensors, and they are even able to detect heart failure in an early phase. In the
      near future the number of pacemaker and ICD implantations will grow exponentially
      based on current trend. This will be due to the aging population, the
      simplification and increasing safety of implantation, and the widening of the
      indications for antiarrhythmic device implantation.

PMID- 15945238
TI  - [Cardiac surgery--2005].
AB  - The demand of the patients and the society, the results of basic sciences and
      industrial developments besides the judgement of the surgeon determine the
      evolution of cardiac surgery. The authors review the actual questions of the main
      disciplines in cardiac surgery. Outcomes of coronary artery surgery are detailed,
      on what the new interventional techniques have enormous influence. In the
      valvular surgery the spreading of plastic surgical procedures and stentless valve
      implantation is to be expected. According to the international surveys the amount
      of heart transplantation stagnates. The usage of long- and short-term mechanical
      support devices is neccessitated. The minimally invasive techniques associated
      with less operative injury can be performed safely with appropriate experience in
      selected patients. The prevention of perioperative brain damage is also
      considered an important issue, and several refinements are tested. Actually we
      are in the phase of acquiring experience; however, it can be compared to
      "shooting a moving target" due to the continuous developments.

PMID- 15945239
TI  - [Present and future of non-invasive cardiologic diagnostics].
AB  - Present echocardiographic techniques are discussed including potential future
      developments. Nowadays, multidetector CT and cardiac MR systems only partially
      used in the cardiology diagnostics. Technical improvement will allow the correct
      imaging of the coronary arteries by both new methods in the near future.
      Noninvasive cardiology diagnosis will be broadened soon by this new developments.

PMID- 15945240
TI  - [Current practice and future perspectives of myocardial stem cell therapy].
AB  - Myocardial infarction became more frequent mainly in the developed countries in
      the past decades. Beside the pharmacological (thrombolysis, beta-blockers, ACE
      inhibitors, antiplatelet- and lipid-lowering drugs, etc.) and interventional
      (percutaneous coronary intervention, intraaortic balloon pump, resynchronization
      therapy, left ventricular assist devices etc.) procedures the quality of life of
      patients and the morbidity and mortality data were improved. However we
      experience development of heart failure following myocardial infarction because
      of significant cell loss and left ventricular remodeling. Until now there was not
      any therapeutic procedure affecting via cardiomyocyte renewal, but in the last 5
      years the myocardial stem cell therapy was introduced to human clinical phase. In
      this review the authors summarized the general features of stem cells, why these
      cells are in the focus of the interest and their preclinical and clinical
      applications in myocardial infarction. Promising issues suggests, that
      intramyocardial implantation of autologous bone marrow derived stem cells become
      a new therapeutic modality in treatment of myocardial infarction. The stem cell
      therapy and regenerative medicine would open new perspectives in cardiology.
      However it is very important to remark, that this, as every medical procedure can
      be dangerous and can cause side effects. A lot of molecular and cellular
      mechanism of cell therapy is not clear at present, that's why we should be
      careful with this opportunity holding in our hands. We have to plan multicenter
      clinical trials to evaluate the long term safety and efficacy of the procedure.

PMID- 15945241
TI  - [Pharmacologic prevention of cardiovascular diseases--2005].
AB  - Cardiovascular diseases are the leading cause of death in Western countries, and
      that is true for Hungary as well, and so will be the case in developing countries
      in 2025. Cardiovascular diseases kill more than 950000 people only in the USA.
      50% of cardiovascular mortality is due to ischemic heart disease, stroke is
      responsible for 20%. The annual cost of the treatment of cardiovascular illnesses
      takes more than 330 billion dollars. All these data underline the importance of
      these illnesses. The aim of cardiovascular prevention is to reduce the incidence
      of first or recurrent events due to ischemic heart disease, ischemic stroke or
      peripheral artery disease, especially early deaths and disability. In the
      following article the medical aspects of cardiovascular prevention are
      summarized. Lifestyle changes and special treatment of particular risk factors
      are out of scope of this review.

PMID- 15945242
TI  - [Multidrug resistance: diagnostic approaches and difficulties].
AB  - During the mid sixties scientists recognized that tumour cells can be resistant
      to a variety of chemotherapeutical drugs of different chemical structure
      simultaneously. They named this phenomenon multidrug resistance (MDR). Following
      this observation, number of in vitro and in vivo experiments proved that
      transmembrane proteins of the cell membrane are responsible for the mechanism.
      Many details of the underlying biochemical mechanisms were explored during the
      past decade. Nowadays the importance of MDR is well appreciated in different
      walks of medical science. MDR is an important problem during the treatment of
      many haematological conditions and solid organ tumors. Also, MDR is an important
      factor during immunosuppressant therapy of the transplanted patients. In spite of
      extensive research there are many uncertainties around MDR. This brief review
      describes the present options in the investigation of MDR. Based upon the MDR
      genotyping and expression level the likelihood of drug resistance may be
      predicted with reasonable accuracy. Additional information may be obtained by
      measuring the P-glycoprotein expression on the cell surface and the outward
      transport of test molecules from the cells. Although the tests described above
      provide significant help in predicting MDR or in the confirmation of existing MDR
      there is no consensus about the laboratory diagnosis.

PMID- 15945243
TI  - [Epilepsy in childhood: diagnosis and therapy].
AB  - Epilepsy in childhood is a very frequent disease. Diagnosis is not easy due to
      many types of provoked seizures in children. The main diagnostic tool is the
      medical history. Home video of the paroxysmal event can help the pediatric
      neurologist, too. The most important laboratory investigation is the EEG but
      sometime it is not informative. The best provocation of EEG is the sleep
      deprivation. It is important to register the electrical activity during sleep
      because in a lot of epileptic syndromes in childhood the pathological
      abnormalities can be seen only during sleep. The prognosis improved due to the
      new antiepileptic drugs and the development of epileptic surgery.

PMID- 15945244
TI  - [The first molecular analysis of a Hungarian HNPCC family: a novel MSH2 germline
      mutation].
AB  - BACKGROUND: Hereditary nonpolyposis colorectal cancer is an inherited disease
      characterized by onset at an early age, an excess of synchronous and metachronous
      large bowel tumors and a variety of extracolorectal malignancies. Basal and
      squamous cell carcinomas of the skin are not customarily included in the tumor
      spectrum of the syndrome. The disease is caused by a germline mutation in one of
      the DNA mismatch repair genes, most commonly MSH2 or MLH1, and typically presents
      with microsatellite instability and frequent loss of mismatch repair protein
      expression in the tumor tissue. PATIENT: The case of a 62-year old woman who had
      a history of colon cancer at the age of 46 years, endometrial cancer at the age
      of 56 years, baso-squamous, and squamous cell cancer of the face at the ages of
      53, 54, 62 and 58 years, respectively, and rectal cancer at 60 is reported. Her
      family fulfills the Amsterdam criteria for the diagnosis of hereditary
      nonpolyposis colorectal cancer. The baso-squamous cell, the squamous cell, the
      endometrial and the rectal cancers were assessed for the microsatellite
      instability status and the expression of the MSH2 and MLH1 mismatch repair
      proteins, and the p53 tumor suppressor protein by immunohistochemistry.
      Mutational screening using an automated capillary DNA sequencer was performed by
      the direct genomic sequencing of 17 fragments of the MSH2 gene, which covers
      promoter, all exons and flanking intronic regions. RESULTS: All cancers displayed
      microsatellite instability and were positive for the p53 protein. The
      immunohistochemical staining in the baso-squamous cell, the squamous cell, the
      rectal and endometrial cancers were negative for MSH2 and positive for MLH1
      proteins. DNA sequencing analysis revealed a mutation c.2292G > A in exon 14 of
      the MSH2 gene, which is altering the 764. amino acid, the tryptophan to STOP
      codon (p.W764X). Thus the MSH2 protein is presumably truncated by 171 aminoacids.
      CONCLUSION: To the best of authors' knowledge, this is the first molecular
      characterization of a Hungarian hereditary nonpolyposis colorectal cancer family.
      According to the Human Mutation Database and International Collaborative Group of
      HNPCC Database, this mutation is novel, has not been reported previously.
      Cutaneous baso-squamous and squamous cell cancers may present as part of the
      HNPCC phenotype. Detection of the loss of mismatch repair protein expression and
      mismatch repair gene mutation mapping, represents a significant improvement of
      the diagnosis of this syndrome in Hungary. These examinations identify the
      mutation carriers who are at an increased risk of developing cancers.

PMID- 15945245
TI  - [Treatment of hypoparathyroidism].

PMID- 15945246
TI  - [Centennial of the birth of Istvan Krompecher].

PMID- 15945247
TI  - [Education in laparoscopic urology. Problems. Solutions].

PMID- 15945248
TI  - [The Cochrane collaboration and the Cochrane library in urology].
AB  - The Cochrane Collaboration is an international, non-profit making organisation
      which aims to help people make well-informed health care decisions. The main
      objective is to prepare, update, promote and facilitate access to systematic
      reviews on health care interventions. The main product is The Cochrane Library, a
      quarterly electronic publication. The principles and structure of the Cochrane
      Collaboration and the structure and content of the Cochrane Library will be
      described. The importance of systematic reviews and meta-analyses as sources of
      information for clinicians will be presented, with special emphasis on the
      contributions of the Cochrane Collaboration to the speciality of urology.

PMID- 15945249
TI  - [Comparative study between cystoscopy, urinary cytology, NMP-22 and a new method,
      bladder chek, in the follow-up of superficial bladder cell carcinoma].
AB  - OBJECTIVE: The goal of this work tries to evaluate the utility of the qualitative
      determination of NMP-22 in the evaluation of the superficial bladder carcinoma in
      asymptomatic patients, comparing it with its quantitative determination, the
      cytology and the cystoscopy. MATERIALS AND METHODS: A simple of urine just voided
      was taken in 88 asymptomatic patient follow-up for superficial bladder cell
      carcinoma. This dose was distributed in 3 parts, for performed cytology, for
      determination of NMP-22, and 4 drops of the third part are added to device
      bladder chek. Later, we performed cystoscopy and transurethral resection in
      patients with a suspicion of bladder cancer. RESULTS: 26 patients had tumor
      relapse and 62 patients were free of disease. The sensitivity for the bladder
      chek was of 28%, 34.62% for NMP-22, 34.62% for cytology and 100% for cystoscopy.
      The specificity was of 93.55%, 80.33%, 87.10% and 87.10% respectively. The
      sensitivity by degree was 25 in G1, 28.57 in G2 and 50 in G3 for Bladder chek;
      29.41, 42.86 and 50 for NMP-22; 23.53, 71.43 and 0 for cytology. The sensitivity
      by stages was 27.7 in Ta-1 and 50 in T2 for Bladder chek; 34.78 and 50 for NMP
      22; 39.13 and 0 for the cytology. CONCLUSIONS: The low sensitivity of bladder
      chek invalidates it like alternative method to the cystoscopy in the follow-up of
      the superficial asymptomatic bladder cell carcinoma.

PMID- 15945250
TI  - [Primary adenocarcinoma of the urinary bladder: our experience].
AB  - Adenocarcinoma of the bladder is an uncommon neoplasm. Depending on its origin it
      is classified in: primary, secondary and urachal. Generally it grows to the
      density of the wall, so its clinical appearence is delayed, with the subsequent
      delayed diagnosis and although an agressive treatment is performed, it frequently
      has a very bad prognosis. Since there are very few publications of this kind of
      neoplasm in the literature the lines of actuation in this pathology are not well
      established. We report the eleven cases of adenocarcinoma neoplasm of the bladder
      treated in our centre and review the literature.

PMID- 15945251
TI  - [Prognostic value for progression of the regulating proteins of the cellular
      cycle in PT1G3 bladder tumours].
AB  - INTRODUCTION AND OBJECTIVE: Bladder tumor T1G3 constitutes the group of
      superficial tumors more aggressive. New prognostic factors in the field of the
      cytogenetics and molecular biology have been analyzed, with often contradictory
      results, being little the specific works in tumors T1G3. Our objective is to
      determine if in this group of tumors the immunohistochemical markers present
      predictive value of clinically useful progression, and therefore with validity to
      indicate more suitable a precocious therapeutic attitude. MATERIAL AND METHODS:
      Retrospective study of a series of 83 patients affected of bladder tumor T1G3, on
      which we analyzed a total of 14 variables; between the new predictive factors:
      the immunohistochemical determination of regulating proteins of the cellular
      cycle: p53, p21 and bcl-2, as well as the Ki-67 protein like marker of cellular
      proliferation. By means of logistic regression analysis we establish the
      independent prognostic variables for tumorlike progression. RESULTS: The cut
      point established for Ki67 and p53 was 40% of inmmunomarked cells, 20% for p21
      and 10% for Bcl-2. The univariant analysis showed different rates from
      progression and free times of progression based on the immunohistochemistry of
      Ki67 and p53: nevertheless, the logistic regression demonstrated that single the
      immunohistochemistry of p53 presented independent predictive value. CONCLUSIONS:
      The determination of p53 presents predictive value of clinically useful
      progression in bledder tumors T1G3, so that its determination can constitute a
      essential factor in the strategies of treatment of these tumors.

PMID- 15945252
TI  - [Local relapse and single site of metastatic involvement of renal tumour.
      Prognostic factors and survival].
AB  - OBJECTIVE: To evaluate the clinical and pathological characteristics and survival
      in patients surgically treated for renal tumours that had local recurrence or
      metastasis to a single site. MATERIAL AND METHODS: A retrospective study of 321
      nephrectomies, evaluating the clinical and pathological variables in patients
      having local recurrence or metastasis to a single site, and who were treated
      surgically. Study and comparison of survival in the different groups. RESULTS:
      The only factor found to have an independent influence on local recurrence is
      pathological stage. Local recurrence and the presence of metastasis to a single
      site have similar survival rates, both being statistically worse than in patients
      without metastasis at diagnosis, but better than in those having metastasis at
      diagnosis. CONCLUSIONS: The presence of local recurrence has the same prognosis
      as a single excisable metastatic site, the prognosis being better than those
      initially with metastasis subjected to nephrectomy before receiving systemic
      treatment.

PMID- 15945253
TI  - [Laparoscopic adrenalectomy in adrenal carcinoma].
AB  - There is general agreement on the suitability of the laparoscopic approach for
      benign adrenal lesions against open procedures because of the efficacy and less
      morbidity. For suspected adrenal malignancies laparoscopic use is controversial.
      We report our experience in 6 cases of laparoscopic adrenalectomy in patients
      with the suspicion of adrenal malignancy confined in the gland. In medium a
      follow up of 24 months (range 12 to 48 months) we observed no recurrences. We
      concluded that in a suspected adrenal malignancy organ confined laparoscopic
      adrenalectomy presents the advantage compared with open surgery of reduced
      morbidity and similar results in the follow up of the patient.

PMID- 15945254
TI  - [Pheochromocytoma with thrombus in cava].
AB  - Pheochromocytoma, a paraganglioma of suprarenal location, is a catecholamine
      secreting chromaffin cell tumour. Spread of these tumours to the vena cava is
      rare and the thrombus only reaches the right atrium in exceptional cases. We
      present the case of a patient who, without previous symptomatology, presented
      with a clinical picture of multiorganic dysfunction with primary manifestation of
      a suprarenal tumour with vascular spread to the right atrium affecting the right
      suprahepatic vein.

PMID- 15945255
TI  - [Results and complications of TVT procedure in the surgical treatment of female
      stress incontinence].
AB  - OBJECTIVES: To evaluate the efficacy and safety of Tension-free vaginal tape
      (TVT) for treatment of female stress urinary incontinence (SUI). To determine the
      mid-term outcome of TVT performed during other pelvic floor reconstructive
      procedures. PATIENTS AND METHODS: 100 women with SUI undergoing TVT procedure
      under spinal anesthesia from January 2000 to November 2002 were studied. 76 women
      were treated with TVT alone. 24 patients were treated with TVT and pelvic floor
      reconstruction: we repaired 24 cystoceles grade II-III, 3 rectoceles and 4
      concomitant vaginal histerectomies. RESULTS: Mean age was 49.3 years (range 35
      78). Mean parity: 2 (range 0-6) and mean operative time was 38 minutes (range 20
      to 50). The postoperative hospital stay was 24 hours for women treated with TVT
      alone. Only 1 patient (1%) need bladder catheterization during 7 days due to
      urinary retention. Mean followup was 18 months (range 12-48). Objective cure rate
      was 95%. In our study the rate of de novo post-operative urge symptoms (16%) was
      the most frequent complication. Bladder injury was the most grave problem and it
      happened in 1 patient (1%). CONCLUSION: The results confirm the feasibility and
      safety of TVT for treatment of SUI. Moreover, TVT procedure is economical and
      efectiveness. Pelvic floor defects, benign uterine disorders and SUI can be
      safely treated with TVT and vaginal procedures during the same surgical time.

PMID- 15945256
TI  - [Modification of nephritic colic and 24-hour calcium excretion in urine in
      primary hyperthyroidism after parathyroidectomy].
AB  - We documented the frequency of nephritic colic in patients with primary
      hyperparathyroidism, and determined its modification after the parathyroidectomy;
      we also studied laboratory parameters such as calcium, phosphorus and parathyroid
      hormone in serum, and the excretion of Cao 24h, previous and later to the
      intervention. At sight of the results it is possible to be concluded that the
      parathyroidectomy is useful in the treatment of the kidney stone disease produced
      by the primary hyperparathyroidism.

PMID- 15945257
TI  - [Endourologic treatment of ureteral strictures. Experimental comparative study].
AB  - OBJECTIVES: To compare efficacy and efficiency of two different endourological
      therapies for ureteral stricture, and to evaluate pathological reactions of the
      ureters following both endourological techniques. MATERIAL AND METHODS: Ten pigs
      underwent experimental induction of ureteral stricture. Four weeks later,
      ureteral strictures were demonstrated by imaging techniques. Animals were divided
      in two groups, according to the received therapy: -Group I. (5 pigs), endoballoon
      rupture endoureterotomy. -Group II (5 pigs), Acucise balloon endoureterotomy.
      Ureteral stents were placed for 3 weeks following endoureterotomy. Animals were
      followed up four weeks after ureteral stents retrieval. RESULTS: In all cases,
      ureteral stricture was proved four weeks after model induction. In one case from
      each group, it was needed a second balloon dilatation to achieve complete
      endoureterotomy. Leading to ureteral restenosis, stent migration occurred in one
      animal from group I. Success was achieved in 80% of cases from group I, and 100%
      of cases from group II. CONCLUSIONS: Our results suggest that both endourological
      therapies are effective. Nevertheless, a higher efficiency was proved with
      Acucise endoureterotomy. Our pathological evidences do not support Davis's
      studies on ureteral healing following endoureterotomy.

PMID- 15945258
TI  - [Urological attendance in the Integral Health Center "Alto Palancia": model of
      primary-specialized integration and unique consultation].
AB  - INTRODUCTION AND OBJECTIVE: The progressive increase in the demand of urological
      attendance demands to establish new welfare models that avoid the saturation of
      consultations and improve the quality in the attention to the user. The objective
      of this work is to analyze the improvement of the welfare activity developed in
      Integral the Sanitary Center Alto Palancia, after the restoration of new welfare
      models based on integration between Attention Primary and Specialized and the
      putting in practice of the denominated Unique Consultation. MATERIAL AND METHODS:
      We analyzed the characteristics of the Center, functions and activity of the
      specialty developed during year 2002. We described to the application of the
      model of Unique Consultation and the elements of integration with Primary
      Attention. We analyzed the improvement of the activity through indicators, that
      we compared with preceding years. In order to determine the degree of
      satisfaction of the users we made a survey of opinion of patients and/or taken
      care of relatives in the Center under the new welfare models. Finally we analyzed
      the advantages that the applied process presents for the patient and the own
      sanitary institution. RESULTS: 42% of patients have been taken care of by means
      of the model of Unique Consultation, being the predominant pathology the HBP in
      the man and the ITUs in the woman. The time of delay for first visit has been
      reduced from 49 days in single December 2001 to 3 in December 2002. Single 7.7%
      of patients discharged from the hospital for pursuit by Primary Attention have
      been sent again to the specialist. The time that the urologo dedicates to
      consultations has reduced in a 29%, being this time dedicated to the
      accomplishment smaller surgery and final reconnaissances (echography, urodynamic
      studies and others). The opinion survey has shown a satisfaction of the user very
      elevated. CONCLUSION: The model of Integral Attention Primary-Specialized and the
      putting in practice of Unique Consultation applicable to the specialty of
      Urology, increasing the quality perceived by the user and with evident advantages
      for the Sanitary Organization.

PMID- 15945259
TI  - [Primitive neuroectodermal tumor. Ewing's sarcoma].
AB  - Primitive neuroectodermal tumor is an extraordinarily rare primary tumor in the
      kidney and can be mistaken for a variety of other round cell tumors. It is
      important to recognize each of these entities, because each carries unique
      therapeutic and prognostic implications. However, accurate diagnosis of these
      tumors is hindered by their significant morphologic overlap and complicated by
      their rarity. These neplasm are highly aggressive that tend to recurence and to
      metastatize. Standard therapy combining surgery, chemotherapy, radiation and
      genetic therapy. We report a case of primitive neuroectodermal tumor of the
      kidney in a 50 year old female patient.

PMID- 15945260
TI  - [Selective arterial embolization in a case of renal cell carcinoma as therapeutic
      choice].
AB  - We show a big renal cell carcinoma case in an aged woman with many pathology
      associated. In view of the family refuse to make the radical surgery and the high
      surgical risk we decided to apply transarterial embolization treatment with
      polivinil alcohol particles (PVA). 28 months later the patient becames with no
      symptoms and with high quality life. We come to the conclusion that embolization
      is an effective therapeutic for the symptoms control in selectionated cases.

PMID- 15945261
TI  - [Burn out bilateral testicular tumor].
AB  - Differentiating a primary retroperitoneal seminoma from a metastatic testicular
      tumor with an occult testicular primary or a burned out testicular cancer remains
      difficult. We present a case of a burned out tumor. The patient had a
      retroperitoneal seminoma with ultrasonically and pathologically demonstrated
      abnormalities in both testes, but without evidence of tumor. The patient received
      chemotherapy and underwent surgery of the residual retroperitoneal mass and
      bilateral orchiectomy. All surgical specimens were negative for testis cancer.
      CONCLUSION: Primary extragonadal germ cell tumors in the retroperitoneum are a
      rare entity. The presence of a retroperitoneal tumor with ultrasonographical
      abnormalities in testicular evaluation should be considered as a metastases of a
      burned out testicular cancer, and biopsy is mandatory. Surgical evaluation and
      orchiectomy should be evaluated in a individual setting.

PMID- 15945262
TI  - [Acute renal ischemia--unusual cause of lumbar pain].
AB  - Acute renal artery occlusion is rarely found in daily clinical practice. Its
      rarity and inespecific clinical presentation are responsible for late diagnosis
      or diagnostic errors, with symptoms frequently being erroneously attributed to
      other more common entities. There is no consensus in what concerns therapeutic
      options. Multiple treatment modalities are described in the available literature.
      Some defend anticoagulant therapy and support measures only while others
      recommend other more invasive alternatives reaching even open surgery. The
      authors present two additional case reports of acute embolic renal ischemia. A
      thorough literature review is also presented comprehending etiological, clinic,
      diagnostic and therapeutic aspects.

PMID- 15945263
TI  - [Urachal pathology: an overview review and report of three clinical cases].
AB  - With the use of these two clinical cases (cyst and urachal adenocarcinoma) we did
      an overview of the urachal pathology. The urachus cyst is usually asyntomathic,
      it's detected randomly when we do other diagnostic tests or when we have any
      complications. The urachal adenocarcinoma is a rare pathology, it usually exhibit
      hematuria and we need to follow the same diagnostic tools as we use in vesical
      tumors (cystoscopy and transurethral vesical resection). Adenocarcinoma of the
      dome of the bladder is the main differential diagnosis. Partial cystectomy is the
      first choice treatment. Quimiotheraphy and radiotheraphy offer poor results.

PMID- 15945264
TI  - [Renal cancer presenting thrombus of the vena cava reaching the right atrium. NMR
      images].

PMID- 15945265
TI  - [Vesical inguinoescrotal hernia detected by scintigraphic screening].

PMID- 15945266
TI  - New contraceptive choices.
AB  - Family planning users and providers have been calling for more choices. They want
      contraceptive methods that provide highly effective protection and at the same
      time cause fewer side effects, cost less, and are easier to use. In response,
      researchers are improving existing contraceptives and developing new ways to
      deliver hormones. Offering a wide range of safe, effective, and convenient family
      planning methods encourages more people to use contraception. Having more choices
      helps ensure that users are satisfied with their family planning method. Most new
      methods reaching the market today result from investments made years ago.
      Virtually all methods undergo a long process of research and rigorous testing for
      safety and effectiveness and must obtain regulatory approvals before becoming
      available.

PMID- 15945267
TI  - OIG signals shift on gainsharing: HCA seeks OK for implant contract.
AB  - Six agreements negotiated in recent months will not be challenged. Quality
      managers concede unfamiliarity with and skepticism about gainsharing. Although
      cost savings are undeniable, the quality impact must be monitored.

PMID- 15945268
TI  - Midwest tops nation in patient safety performance.
AB  - Eleven out of 12 states in the Midwest were ranked highest in terms of patient
      safety. Focuses on performance improvement, public reporting are seen as keys to
      a high ranking. Latest figures show decided shift away from Southern states,
      which had been leaders.

PMID- 15945269
TI  - Hospital treats patients and families like VIPs.
AB  - Decision to emphasize patients keeps hospital true to its mission. Proponents
      expect to see success reflected in patient satisfaction numbers. Stress relief
      also may serve to benefit the health of hospital patients.

PMID- 15945270
TI  - Quality directors give QIOs high marks in new study.
AB  - Study includes input from 100 randomly selected quality managers. Hospitals
      indicate 92% satisfaction in Centers for Medicare & Medicaid Services-funded
      telephone survey. Quality improvement organizations are seeking to increase
      involvement of physicians and executives in quality initiatives.

PMID- 15945271
TI  - Is cardiac care better at specialty hospitals?
AB  - Patient mortality rates and lengths of stay were comparable for specialty and
      general hospitals that perform similar volumes of the procedures. Findings were
      similar when comparing high-volume general hospitals and high-volume specialty
      hospitals. Other measures of quality (i.e., use of aspirin, beta-blockers, ACE
      inhibitors) may be more significant.

PMID- 15945272
TI  - Nitrofurazone-induced gene expressions in rat hepatocytes and their modification
      by N-acetylcysteine.
AB  - The antibiotic nitrofurazone (NF) at a subtoxic dose has been shown to increase
      hepatocyte DNA synthesis with no preceding cell damage or necrosis. This was
      suppressed by concomitant administration of the antioxidant N-acetylcysteine
      (NAC), which suggests that free radical production is involved in the process. In
      this study, male F344 rats were given a single oral subtoxic dose of NF to
      investigate the changes in genes implicated in hepatocyte proliferation between 1
      and 20h postdose by real-time PCR. Some rats were also given NAC to examine the
      involvement of free radicals. There were transient and sequential increases in
      mRNA levels of c-myc and c-jun shortly after the administration, followed by
      tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-alpha (TGF
      alpha), c-Ha-ras, and cyclin E. The increases were blocked by concomitant
      administration of NAC. In contrast, there were no NF-specific increases in c-fos,
      hepatocyte growth factor, epidermal growth factor or cyclin D1 mRNAs. These
      results indicate that the induction of hepatocyte proliferation by NF is
      triggered by free radicals, with a pathway involving increases in c-jun, c-myc,
      TNF-alpha, TGF-alpha, c-Ha-ras, and cyclin E. The results also indicate that NF
      induced proliferation resembles that of other mitogens.

PMID- 15945273
TI  - NO2-induced airway inflammation is associated with progressive airflow limitation
      and development of emphysema-like lesions in C57bl/6 mice.
AB  - The major features of chronic obstructive pulmonary disease (COPD) comprise a not
      fully reversible airflow limitation associated with an abnormal inflammatory
      response, increased mucus production and development of emphysema-like lesions.
      Animal models that closely mimic these alterations represent an important issue
      for the investigation of pathophysiological mechanisms. Since most animal models
      in this area have focused on specific aspects of the disease, we aimed to
      investigate whether exposure of C57BL/6 mice to nitrogen dioxide (NO2) may cause
      a more complex phenotype covering several of the characteristics of the human
      disease. Therefore, mice were exposed to NO2 for 14h each day for up to 25 days.
      Initial dose response experiments revealed the induction of a significant
      inflammatory response at a dose of 20 ppm NO2. Mice developed progressive airway
      inflammation together with a focal inflammation of the lung parenchyma
      characterized by a predominant influx of neutrophils and macrophages. In
      addition, goblet cell hyperplasia was detected in the central airways and
      increased collagen deposition was found in the lung parenchyma. NO2-exposed mice
      developed emphysema-like lesions as indicated by a significantly increased mean
      linear intercept as compared to control mice. Finally, the assessment of lung
      functional parameters revealed the development of progressive airway obstruction
      over time. In conclusion, our data provide evidence that the inflammatory
      response to NO2 exposure is associated with increased mucus production,
      development of airspace enlargement and progressive airway obstruction. Thus, NO2
      exposed mice may serve as a model to investigate pathophysiological mechanisms
      that contribute to the development of human COPD.

PMID- 15945274
TI  - Maternal effects and cancer risk in the progeny of mice exposed to X-rays before
      conception.
AB  - To investigate in an animal model whether preconceptual X-ray exposure leads to
      an altered tumor rate and spectrum in the offspring, a transgeneration
      carcinogenesis study was carried out. Female mice received X-ray irradiation (2 x
      2 Gray) 2 weeks prior to mating with untreated males. After weaning, half of the
      descendants were exposed for 6 months to the immunomodulating and tumor-promoting
      compound cyclosporine A (CsA) by diet, the others remained untreated. The animals
      were maintained for their entire lifespan, terminal sacrifices were carried out
      after 28 months. Complete autopsy was performed, and three protocol organs (lung,
      liver and spleen) were examined histologically, together with any suspicious
      lesions in other organs. Fertility and the lifetime of the maternal mice were
      reduced by the X-ray irradiation, and their incidence of lung and liver tumors
      was increased as compared to non-irradiated mice. The descendants of all groups
      revealed comparable body weights and mortality rates. The incidence of
      hematopoietic/lymphoreticular tissue tumors increased in the female hybrids by 6
      months of CsA-treatment. A higher incidence of lung and liver tumors in the sham
      treated male progeny of irradiated mothers was detected, pointing to a possible
      germ cell-transmitted alteration initiated by the preconceptual maternal X-ray
      exposure.

PMID- 15945275
TI  - Changes in histology and expression of cytokines and chemokines in the rat lung
      following exposure to ovalbumin.
AB  - Brown Norway (BN) and Fischer 344 (F344) rats were exposed to aerosol of 1%
      ovalbumin (OVA) solution for 30 min at 1 week after the second sensitization with
      1 mg of OVA at 2-week intervals. Changes in the histology and expression of
      cytokines and chemokines in the lung were examined for up to 96 h after the
      exposure. The lung weight significantly increased in BN rats but not in F344
      rats. Histologically, in the lung of BN rats, multiple foci of hemorrhage in the
      alveolar space with infiltration of eosinophils and macrophages in the
      surrounding alveolar septa were first observed. Thereafter, granulomatous lesions
      developed in the preexisting hemorrhagic foci, finally resulting in formation of
      multiple eosinophilic granulomas. On the other hand, in F344 rats, infiltration
      of eosinophils and macrophages was observed around the vessels and bronchi.
      Thereafter it progressed gradually, resulting in mild thickening of alveolar
      septa. The levels of Th1- (interferon-gamma and interleukin 2 (IL-2)) and Th2
      related cytokines (IL-4 and IL-5) and chemokines (eotaxin and monocyte
      chemoattractant protein-1) mRNAs measured by reverse transcription-polymerase
      chain reaction method were elevated in the lung of both strains, and the levels
      were higher in BN rats than in F344 rats. These results suggest that BN rats are
      more sensitive to OVA-sensitization/inhalation than F344 rats and that the
      difference in the severity of lung lesions between BN and F344 rats may reflect
      the difference in the expression levels of cytokines and chemokines between these
      two strains.

PMID- 15945276
TI  - Saturated free fatty acid, palmitic acid, induces apoptosis in fetal hepatocytes
      in culture.
AB  - To investigate the effects of saturated free fatty acid, palmitic acid (PA), on
      hepatocytes, we administered PA to rat hepatocytes. We demonstrated that PA
      inhibited the cell growth as a dose- and time-dependent manner in rat
      hepatocytes. PA-induced morphological changes including swelling, membrane
      dissolution and formation of debris, and apoptosis with appearance of sub-G1
      fraction determined by cell cycle analysis after treatment for 4 days. The level
      of Bcl-2 was slightly decreased, in contrast, the level of Bax elevated markedly,
      which resulted in a significant decrease of Bcl-2/Bax ratio after PA treatment on
      HepG2 cells. These findings demonstrated that PA induces cell death on
      hepatocytes, perhaps via mitochondria-mediated apoptosis. Furthermore, the
      present study indicates that PA's cell toxicity may play important roles in the
      transition from steatosis to steatohepatitis in human especially with obesity.

PMID- 15945277
TI  - Antioxidant and detoxifying enzymes in the liver of rats after subchronic
      inhalation of the mixture of cyclic hydrocarbons.
AB  - The activity of antioxidant and detoxifying enzymes, superoxide dismutase (SOD),
      glutathione peroxidase (GSHPx), glutathione-S-transferase (GST), the SOD
      isoenzyme patterns and the contents of thiobarbituric acid reactive substances
      (TBARS), were determined in the livers of male and female rats after subchronic
      inhalation of mixtures of benzene, cyclohexanone and cyclohexane. Except for
      decreased GSHPx (with substrate cumene hydroperoxide) and GST activities in
      female rats, no differences in the activities of antioxidant and detoxifying
      enzymes and TBARS content occurred. Between the activities of GSHPx and GST was
      observed an indirect relationship. The activities of GSHPx-cum and GST were
      influenced by sex.

PMID- 15945278
TI  - Effect of Aronia melanocarpa fruit juice on indomethacin-induced gastric mucosal
      damage and oxidative stress in rats.
AB  - Aronia melanocarpa fruits are rich in phenolic substances-mainly flavonoids from
      the anthocyanin subclass. The anthocyanins are water-soluble plant pigments with
      antioxidant, anti-inflammatory, antimicrobial, hepatoprotective, gastroprotective
      and other activities. We studied the effect of A. melanocarpa fruit juice (AMFJ)
      on indomethacin-induced gastric mucosal damage in rats and its possible relation
      to the oxidative status. AMFJ (5, 10 and 20 ml kg(-1)) was applied orally as a
      pretreatment 1 h before the subcutaneous administration of indomethacin (30 mg
      kg(-1)). Gastric ulcer formation was estimated morphometrically and
      histopathologically 4h after the indomethacin administration. Malondialdehyde
      (MDA) in rat plasma and gastric mucosa and also reduced glutathione (GSH) and
      oxidized glutathione (GSSG) in gastric mucosa were determined and used as
      biochemical markers of the oxidative status. AMFJ-pretreatment diminished the
      number and area of indomethacin-induced gastric lesions. Histopathological
      examination of rat stomachs demonstrated that AMFJ induced an increase in gastric
      mucus production and a reduction of the depth and severity of indomethacin
      induced mucosal lesions. AMFJ dose-dependently reduced the elevated indomethacin
      plasma and gastric MDA levels and at the doses of 10 and 20 ml kg(-1) they were
      not significantly different from the control values. Neither indomethacin
      treatment, nor AMFJ-pretreatment had a significant influence on GSH and GSSG
      gastric mucosal levels. These results demonstrated that indomethacin-induced
      gastric mucosal damage was accompanied by the development of oxidative stress,
      evidenced by the accumulation of MDA. AMFJ-pretreatment decreased the gastric
      lesions caused by indomethacin. It could be suggested that this effect of AMFJ
      was probably due to the increased mucus production and interference with
      oxidative stress development as evidenced by the decreased plasma and gastric
      mucosal MDA.

PMID- 15945279
TI  - Menadione protects gastric mucosa against ethanol-induced ulcers.
AB  - Previous studies have shown a definite role of mitogen activated protein kinase
      (MAPK) and epidermal growth factors (EGF) in the maintenance and repair of
      gastric mucosa. The aim of this study is to investigate the effect of menadione,
      an activator of MAPK pathway, on gastric acid secretion and experimentally
      induced gastric ulcer in rats. Acid secretion studies were undertaken using
      pylorus-ligated rats pretreated with menadione (5 - 45 mg/kg, i.p.). The effect
      of orally administered menadione on ethanol-induced gastric ulcers was also
      examined. The level of gastric wall mucus, non-protein sulfhydryls (NP-SH) and
      myeloperoxidase (MPO) was measured in the glandular stomach of rats following
      ethanol-induced gastric lesions. There was a significant inhibition of gastric
      acid secretion in the menadione treated rats. Pretreatment of rats with menadione
      significantly protected gastric mucosa against ethanol-induced gastric lesion. A
      significant attenuation of ethanol-induced reduction of gastric wall mucus,
      depletion of NP-SH and increase in gastric MPO activity was also observed in
      menadione treated rats. In conclusion, this study clearly showed acid
      antisecretory and antiulcer activity of menadione. Further studies are warranted
      to determine the mechanism of antiacid and gastroprotective effect of menadione.

PMID- 15945280
TI  - Knowledge of diet and anthropometry of arctic children provides opportunities for
      improvement.

PMID- 15945281
TI  - Review of vitamin D deficiency during pregnancy: who is affected?
AB  - OBJECTIVES: Vitamin D deficiencies have been documented in several populations,
      including aboriginal Canadians from isolated northern communities. Such
      deficiencies can impact the health of both the mother and her infant. This review
      was performed to determine how widespread vitamin deficiency is during pregnancy.
      STUDY DESIGN: Electronic literature search. METHODS: A Medline search was
      conducted using the Mesh terms "pregnancy" and "vitamin D". Those studies meeting
      the inclusion criteria were reviewed. RESULTS: 35 of 76 studies reported
      deficient mean, or median, concentrations of 25(OH)D. Low concentrations were
      reported among different ethnic groups around the world. In addition, deficient
      concentrations were identified in 3 northern First Nations communities in
      Manitoba. CONCLUSIONS: Such deficiencies are of concern, as the developing fetus
      acquires its 25(OH)D across the placenta and may influence infant health. Future
      research is required to resolve the discourse surrounding ambiguous threshold
      values for vitamin D deficiencies and insufficiencies and to identify effective
      strategies to improve the vitamin D status of expectant women. Vitamin D
      supplementation may be necessary for many women during pregnancy, especially
      those in northern regions where endogenous synthesis may be constrained.

PMID- 15945282
TI  - Exposure of Arctic populations to methylmercury from consumption of marine food:
      an updated risk-benefit assessment.
AB  - Recent and powerful epidemiological studies have been used as a basis for
      revising international and domestic guidelines for human exposure to mercury.
      Long-range transport of mercury into the Arctic makes some Arctic peoples
      consuming traditional marine foods, especially newborns, children and pregnant
      women, very vulnerable to harmful exposures. The WHO, the USEPA and Health Canada
      have all recently revised their mercury intake guidelines as a result of
      neurological effects reported in children exposed in utero and adults. Guidance
      values are equivalent to 0.23 microg/kg-bw/d, 0.1 microg/kg-bw/d and 0.2
      microg/kg-bw/d respectively. Differences between the numbers represent slight
      differences in the uncertainty factors applied, rather than in toxicological
      interpretation. More recent findings suggest that mercury may also be a factor in
      ischemic heart disease, which could lower guidance values in the future.
      Considering the benefits of marine fatty acids (n-3 fatty acids) and guidance
      that populations consume 300-400g fish/week, consumers face a reality that most
      open ocean and relatively 'unpolluted' fish species contain levels of mercury
      that would lead to exposures at current guidance levels. Clearly, there is no
      more room for further mercury pollution and there is an urgent need for
      international action to reduce mercury emissions. Concomitantly, while there may
      be a need for public health authorities to provide consumption advisories to some
      highly exposed populations, such as in the Arctic, there remains a need to better
      understand the interactions and benefits associated with marine foods that may
      reduce health risks associated with low-level mercury exposure.

PMID- 15945283
TI  - Food use of Dene/Metis and Yukon children.
AB  - OBJECTIVE: To describe food use of Dene/Metis and Yukon children with focus on
      food sources--traditional food (TF) and market food (MF), season, gender and
      location. STUDY DESIGN: Children of 10-12 years of age were interviewed for 24-h
      recalls (n = 222 interviews) in five communities during two seasons in 2000-2001.
      METHODS: Differences in children's food and nutrient intakes when consuming or
      not consuming at least one item of TF and across three regions were tested using
      ANCOVA after rank transformation of raw values. Food use was described and
      compared by food groups. RESULTS: MF was the major portion of the diet, with TF
      contributing only an average 4.3%-4.7% of energy in the two seasons. Most TF was
      in the form of land animal meats. More than half of the energy intake from MF
      came from less nutrient dense food items. In spite of low TF intake, children who
      consumed TF had significantly (P < or = 0.05) more protein, iron, zinc, copper,
      magnesium, phosphorus, potassium, vitamin E, riboflavin and vitamin B6 than those
      who did not. Children in the more northern communities consumed significantly (P
      < or = 0.05) more TF, protein, iron, copper, vitamin B6 and manganese, and less
      energy, fat, saturated fat and sodium. CONCLUSIONS: Extensive use of less
      nutrient-dense food by children is a concern, suggesting a need for dietary
      improvement. Use of more TF should be encouraged, especially for children living
      in more southern Arctic communities near commercial centers.

PMID- 15945284
TI  - Dietary nutrients and anthropometry of Dene/Metis and Yukon children.
AB  - OBJECTIVE: To describe nutrient intakes and anthropometry of 10-12-year-old
      Dene/Metis and Yukon children in the Canadian Arctic. STUDY DESIGN: 24 h-recall
      interviews (n = 222 interviews) were conducted on Canadian Dene/Metis and Yukon
      children in five communities during two seasons in 2000-2001; the children were
      measured for height and weight (n = 216). METHODS: Assessment of nutrient
      adequacy used Dietary Reference Intakes (DRIs) including cut-point procedures.
      Anthropometric measurements (height and weight) were assessed and body mass index
      (BMI) was compared to the 2000 CDC Growth Charts. RESULTS: Thirty-two percent of
      the children were above the 85th percentile of BMI-for-age. More than 50 percent
      of children were below the Estimated Average Requirement (EAR) for vitamins A and
      E, phosphorus and magnesium; mean intakes were below the Adequate Intake (AI) for
      vitamin D, calcium, dietary fiber, omega-6 fatty acids, and omega-3 fatty acids.
      Nutrients that were probably adequate for some gender/season groups were protein,
      carbohydrate, iron, copper, selenium, zinc, manganese, riboflavin and vitamins B6
      and C. CONCLUSIONS: Excessive prevalence of overweight and inadequacy of some
      nutrients were observed among Dene/Metis and Yukon children, suggesting a
      necessity for dietary improvement. However, many nutrients were adequate, in some
      cases probably due to continued traditional food use.

PMID- 15945285
TI  - Changes since 1980 in body mass index and the prevalence of overweight among
      inschooling children in Nuuk, Greenland.
AB  - OBJECTIVE: The aim of the study was to examine the trends which have occurred
      during the past generation in body mass index (BMI) and in the prevalence of
      overweight and obesity among children in public schools in Nuuk, Greenland. STUDY
      DESIGN: The study is a retrospective cohort study of BMI among inschooling
      children (age 6 or 7 years old). A database was created on the basis of files
      from school-nurses containing information on height and weight among children
      having attended school in Nuuk since 1970. The database contained 10,121
      measurements in total, whereas 2,801 were on inschooling children. Measurements
      from these children form the basis of this study. Mean and quartiles of BMI among
      the inschooling children in 5-year intervals were used to determine the
      development in BMI since 1980. On the basis of international cut-points for use
      among children and adolescents, the proportion of overweight and obese children
      and the trends since 1980 were determined. RESULTS: The mean BMI has risen by a
      total of a bit more than 6% since 1980, corresponding to a rise of 1.2-3.8% for
      every 5-year period. Increases are also observed when assessing the proportion of
      overweight and obese, which were 6.6% and 0.9%, respectively, among the
      inschooling children during the period 1980-1984. These proportions increased to
      16.5% and 5.2%, respectively, in 2000-2004. CONCLUSION: This study has provided
      evidence that during the past two decades, children in Nuuk have undergone a
      development towards a higher prevalence of overweight and obesity.

PMID- 15945286
TI  - Body mass index may overestimate the prevalence of overweight and obesity among
      the Inuit.
AB  - Body mass index (BMI) is a widely used body weight classification system but has
      known limitations, and may need to be adjusted for sitting height in order to be
      useful as an indicator of health risks in special populations. Data confirm that
      Inuit and Far East Asians have shorter legs and relatively higher sitting heights
      compared with all other populations. Using standing height alone to calculate the
      BMI may overestimate the number of individuals that are overweight and obese, and
      at risk for type 2 diabetes mellitus and cardiovascular disease among the Inuit.
      Measuring sitting height allows for the calculation of a sitting height-to
      standing height ratio (SH/S) which can be used to correct the observed BMI.
      Incorporating sitting height measurements into health research could help
      formulate Inuit-specific screening guidelines.

PMID- 15945288
TI  - Pilot study on potential degradation of drug efficacy resulting from Antarctic
      storage, transport and field conditions.

PMID- 15945287
TI  - Language policies: instruments in cultural development and well-being.
AB  - OBJECTIVES: To measure social capital in one multilingual region of northern
      Sweden. Earlier studies have neglected the language aspect of social capital
      development. To map cultural production (song, literature, theatre) in Meankieli,
      Finnish, Saami and Swedish in the Swedish Torne Valley. METHODS: Statistical
      comparison of regions. Cultural statistics from electronic libraries are related
      to language policies, density of voluntary associations, unemployment, sickness
      and life expectancy. Lists of voluntary associations from municipality
      authorities. STUDY DESIGN: The multilingual region contains five municipalities
      which are related to each other. Two monolingual regions are cited as references
      for the study: Finnish Torne Valley and parts of county Vasterbotten. RESULTS:
      Pajala has the best institutionalisation of the former vernacular Meankieli.
      Saami gains best institutional support in Kiruna. Gallivare has the weakest
      interest to maintain any minority language, whereas Haparanda promotes Finnish in
      education and administration. Overtornea has some interest in Finnish and
      Meankieli. Cultural production corresponds with the institutionalisation of
      Meankieli and Saami and develops best in Pajala and Kiruna. Haparanda and
      especially Gallivare have weak cultural activities in Meankieli, Finnish, Saami
      and Swedish. Finnish is a common, formal, administrative language in Haparanda,
      but is only occasionally used in cultural domains. However, the monolingual
      regions have higher cultural production and seem to have denser networks of
      voluntary associations. Since the 1980s, the cultural index is highest in the
      multilingual region. CONCLUSIONS: Former discriminative language policies have,
      most likely, hamperered development of the civil society in the multilingual
      region, which has seemingly had an influence on unemployment and well-being. The
      monolingual region has less unemployment, (earlier) better health and better life
      expectancy for males. There are, however, indications that the revitalisation of
      the minority language effects positively on socio-economic conditions.

PMID- 15945289
TI  - Perinatal care in the Komi Republic, a sparsely populated region of the Russian
      Federation.

PMID- 15945290
TI  - NY health plan, doctors partner on pay for performance system.

PMID- 15945291
TI  - Geisinger checklist speeds transfer of heart attack patients.
AB  - In cardiology, there is a saying that "time is muscle." The longer it takes to
      reopen a heart attack patient's blocked artery, the more damage is done to the
      heart muscle. Cardiologists and emergency department physicians at Geisinger
      Medical Center are working together to shorten the time that it takes for
      patients to receive angioplasty, thus saving more heart muscle.

PMID- 15945292
TI  - California hospital drops surgical infection rate to zero.
AB  - In 2003, the 448-bed Glendale Adventist Medical Center had a cardiac deep wound
      infection rate of 7%. Just a year later, the hospital succeeded in lowering that
      infection rate to zero.

PMID- 15945293
TI  - Duke University Hospital uses rapid deployment to implement CPOE, clinical
      decision support.
AB  - These are trying times for advocates of computerized physician order entry
      (CPOE). A recent study in JAMA identified more than 20 types of error risks that
      were caused by a CPOE system. Market research indicates that fewer than 10% of
      provider organizations have implemented CPOE systems, with very slow growth
      forecast. But the rapid--and so far, successful--deployment of a CPOE with a
      clinical decision support component at Duke University Hospital shows a more
      positive side.

PMID- 15945294
TI  - Heart failure program expands reach to more hospitals.

PMID- 15945295
TI  - [Endocrinology of aldosterone].
AB  - Aldosterone is the major mineralocorticoid hormone produced by the zona
      glomerulosa of the adrenal cortex. Aldosterone secretion is mainly regulated by
      the renin-angiotensin system, and to a minor extent by serum concentration of
      potassium, sodium, adrenocorticotropic hormone. and dopamine. This hormone, as
      well as other adrenal corticosteroids, exert many of its physiological actions
      through modulation of gene expression. It binds cytosolic receptors that
      translocate to the nucleus in a ligand-dependent manner and induces transcription
      of specific genes that encode for proteins involved in the cardiovascular
      homeostasis. Such proteins act regulating vascular tone, sympathetic nervous
      system activity, and hydroelectrolyte transport in epithelial tissues. Classical
      aldosterone target tissues are kidney, colon, sweat and salivary glands. Apart
      from the genomic effects, which imply a direct action on DNA, rapid non-genomic
      actions of aldosterone have been recently described in both epithelial and non
      epithelial tissues and structures such as heart, vasculature, and kidney. At
      these sites aldosterone contributes to the development of cardiac fibrosis,
      myocardial hypertrophy, heart failure and arrhythmias; other deleterious effects
      exerted by aldosterone include vascular remodeling, endothelial dysfunction,
      perivascular inflammation, renal fibrosis, and progressive renal failure.
      Finally, recent evidence has focused on the possible implications of aldosterone
      excess on metabolic alterations, as described in patients with primary
      aldosteronism. On these premises lies the pathogenetic role of aldosterone in the
      development of cardiovascular diseases and the rationale for the use of
      mineralocorticoid receptor antagonists in the primary and secondary prevention of
      the complications related to these diseases.

PMID- 15945296
TI  - [Activation of the renin-angiotensin-aldosterone system in heart failure].
AB  - Several studies have demonstrated that a prolonged over-activation of
      neurohormonal mechanisms contributes to drive structural and functional
      abnormalities of the cardiovascular system and leads to poor prognosis in
      patients with congestive heart failure (CHF). In particular, activation of the
      renin-angiotensin-aldosterone system (RAAS) leads to increased levels of
      angiotensin II and plasma aldosterone, and promote development of arterial
      vasoconstriction and remodeling, sodium retention, oxidative process, and cardiac
      fibrosis. Angiotensin-converting enzyme inhibitors or angiotensin II receptor
      blockers and beta-blockers may modulate this excessive over-activity and improve
      survival in those patients. However, high circulating and tissue levels of
      angiotensin II and aldosterone may persist and contribute to further progression
      of CHF. Many aspects of the pathophysiological role of the RAAS in CHF are still
      debated, and a more thorough comprehension of this fundamental system is needed.
      This article reviews the current knowledge on the biochemical and functional
      organization of the RAAS, its pathophysiological role in CHF, and the potential
      therapeutic implications.

PMID- 15945297
TI  - [The problem of sudden death in heart failure].
AB  - Sudden death, due to malignant ventricular arrhythmias, is a major problem in
      heart failure. Mortality increases with NYHA functional class, but the relative
      percentage due to sudden death is higher in lower NYHA functional classes (50-80%
      in NYHA class II, 30-50% in NYHA class III, and 5-30% in NYHA class IV). No
      antiarrhythmic drug is useful to prevent sudden death. In coronary artery disease
      revascularization reduces mortality in multivessel disease. In all patients with
      heart failure many drugs are useful in reducing total mortality and sudden death:
      beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor
      blockers, antialdosterone drugs, statins, and omega-3 fatty acids. Finally, many
      prospective randomized studies have demonstrated the efficacy of implantable
      cardioverter-defibrillators in reducing mortality. However, the high cost-benefit
      ratio remains an unsolved problem of this therapy.

PMID- 15945298
TI  - [Aldosterone blockade in essential hypertension].
AB  - The interest in the therapeutic potential of aldosterone antagonists in essential
      hypertension comes from the recently discovered nonclassical pathways of
      aldosterone actions, above all the presence of extra-adrenal aldosterone
      production and the discovery of aldosterone proinflammatory and profibrotic
      actions. The review begins with the discussion of experimental studies on
      animals, demonstrating the role of aldosterone in cardiovascular remodeling and
      the effects of aldosterone blockade on hypertensive target organ damage. Then
      recent clinical studies are presented, that confirm in humans the deleterious
      role of aldosterone, in particular in the development of myocardial hypertrophy,
      cardiovascular fibrosis and arterial stiffness. Finally the results of clinical
      studies on essential hypertensive patients are discussed, evaluating the efficacy
      of aldosterone antagonists in lowering blood pressure, but, more important, in
      protecting against target organ damage.

PMID- 15945299
TI  - [The role of aldosterone in the development of postinfarction fibrosis].
AB  - Aldosterone was discovered in 1953, and until the beginning of the 1960s, when
      spironolactone was developed, it was the focus of considerable interest among the
      scientific community. The following 30 years represented a sort of Dark Age,
      interrupted by the Weber's classic studies. He first demonstrated the pivotal
      role of aldosterone in the promotion of cardiac hypertrophy and fibrosis and such
      an observation represented a solid background for the implementation of large
      survival trials, the RALES and the EPHESUS. These landmark studies showed that
      aldosterone receptor blockade prolongs survival in advanced and postinfarction
      heart failure, respectively. After a myocardial infarction, there is a
      significant upregulation of the local steroidogenic system in the area remote
      from the scar, that leads to a remarkable fibroblast activation, collagen
      deposition, and reactive fibrosis. Fibrosis in turn further impairs systolic and
      diastolic function, and induces electrical heterogeneity with attendant ominous
      arrhythmias. The following review will dwell upon the importance of fibrosis in
      postinfarction heart failure, the role of aldosterone, and the novel therapeutic
      approach based on mineralocorticoid receptor blockade.

PMID- 15945300
TI  - [Tolerability and efficacy of aldosterone inhibition with canrenone in heart
      failure: the real-world experience of an outpatient heart failure clinic].
AB  - BACKGROUND: The aim of this study was to evaluate retrospectively the
      tolerability, safety and efficacy of antialdosterone therapy in patients with
      heart failure admitted to our ambulatory from June 1995 to September 2003.
      METHODS: One hundred and fifty-seven consecutive patients (mean age 64 +/- 11.6
      years) were enrolled in the study; they were in NYHA class I-IV, on ACE-inhibitor
      or angiotensin receptor blocker therapy, and were treated with canrenone if they
      were in NYHA class I-IV having experienced a previous cardiac event and did not
      show asymptomatic left ventricular dysfunction or creatinine levels at baseline >
      or = 2.5 mg/dl, hyperkalemia > or = 5.2 mEq/l, and poor compliance. The mean
      follow-up was 38.7 +/- 21.2 months. Patients were divided into two groups
      according to either therapy (group 1: 124 patients, 79%, on antialdosterone
      therapy; group 2: 33 patients, 21%, on no antialdosterone therapy) or ischemic
      and non-ischemic etiology (group A: 71 patients, 45.2%, and group B: 86 patients,
      54.8%, respectively). Serum creatinine and plasma potassium levels, left
      ventricular ejection fraction, NYHA class, adverse effects, and mortality were
      evaluated. RESULTS: The mean dose of canrenone was 37 +/- 19.9 mg/day. Creatinine
      levels did not change significantly whereas potassium levels slightly increased
      in group 1 vs group 2 (p < 0.01) and in group A vs group B (p < 0.01). Treatment
      was discontinued by only 12 patients (8.1%) due to hyperkalemia in 8 cases
      (6.5%), gynecomastia in 2 cases (1.6%), urticaria in 1 case (0.8%), and nausea in
      1 case (0.8%). Left ventricular ejection fraction increased in all groups (p <
      0.001) with the exception of the subgroup B/group 2 (p = NS). The NYHA class
      improved significantly in group 1 (p < 0.01). The total mortality rate was 10.8%
      (17 cases), of which 10.5% (13 cases) in group 1 and 12.1% (4 cases) in group 2
      and due to sudden death in 3 group 1 patients (2.4%) and in 2 group 2 patients
      (6%). CONCLUSIONS: This study shows a good tolerability, safety, and efficacy,
      and poor adverse effects of canrenone therapy in combination with ACE-inhibitors,
      angiotensin receptor blockers and beta-blockers in patients with chronic heart
      failure. Therapy should be monitored by serial clinical and laboratory controls
      and gradually titrated up to the maximal tolerated dosage.

PMID- 15945301
TI  - [The AREA IN-CHF trial (antiremodeling effect of aldosterone receptors blockade
      with canrenone in mild chronic heart failure): rationale and design].
AB  - The RALES study has shown that spironolactone reduces the risk of morbidity and
      mortality both from progressive heart failure and sudden death in patients with
      NYHA class III or IV heart failure. This favorable effect was clearly independent
      of a diuretic effect. EPHESUS extended these results to eplerenone in patients
      with acute myocardial infarction complicated by left ventricular dysfunction and
      signs of heart failure. Antialdosterone drugs may be effective because they
      oppose the effects of aldosterone to sodium retention, loss of magnesium and
      potassium, sympathetic activation, baroreceptor function and vascular compliance.
      Antialdosterone treatment may also antagonize the effect of aldosterone in
      promoting cardiac fibrosis. In a RALES substudy baseline serum PIIINP, a marker
      of extracellular matrix turnover, showed an independent negative correlation with
      survival and chronic heart failure hospitalizations in the placebo group.
      Therefore it seems interesting to evaluate the effect of canrenone, an
      aldosterone receptor blocker, on the progression of left ventricular dysfunction
      in patients with mild heart failure assuming standard therapy.

PMID- 15945302
TI  - Prosthodontics: have we misjudged the cause and lost direction?

PMID- 15945303
TI  - A retrospective study of the prosthodontic management of patients with
      amelogenesis imperfecta.
AB  - PURPOSE: This article reports on a retrospective study on patients with a
      diagnosis of amelogenesis imperfecta and on their prosthodontic management, oral
      health status, and attitudes toward their condition. MATERIALS AND METHODS: The
      study comprised 15 patients and consisted of a clinical evaluation and
      questionnaire. Clinical examination included records of types of restorations and
      cements used, rating of restoration quality, as well as complications and
      periodontal variables. RESULTS: The 15 patients had a total of 213 prosthetic
      restorations. The median age of the restorations was 60 months. Following the
      California Dental Association's system, all restorations were rated as acceptable
      to excellent, with one exception. During the follow-up period, four (2%)
      restorations had been recemented and 16 (8%) restorations had been redone, five
      (2%) because of porcelain fractures and 11 (5%) because of caries; two (1%)
      endodontic treatments were performed after prosthetic restoration. Plaque and
      Bleeding Indices were 28% and 21%, respectively, while pocket depths of more than
      3 mm were found at 7% of all tooth surfaces. All patients judged their condition
      as having affected them negatively. However, after prosthodontic rehabilitation,
      patients experienced an improvement in self-esteem. CONCLUSION: Patients with
      severe clinical manifestations of amelogenesis imperfecta obtained extensive
      prosthodontic treatment at an early age. The restorations had in general
      performed well, and all patients were affected positively as a result.

PMID- 15945304
TI  - Maxillary interim overdentures retained by splinted or unsplinted provisional
      implants.
AB  - PURPOSE: The survival rate of splinted and unsplinted provisional implants for
      anchoring removable interim overdentures, as well as handling and maintenance of
      the interim dentures, was evaluated. MATERIALS AND METHODS: Eighteen edentulous
      maxillae were provided with 72 provisional implants for anchoring interim
      overdentures. For 10 patients, 40 unsplinted implants were used with conical
      copings to retain the provisional prostheses, while for 8 patients 32 implants
      had a splinted bar architecture for supporting the interim prostheses. Failure
      rate of provisional implants, as well as handling and behavior of the anchored
      interim overdentures, was followed until definitive prosthetic restoration and
      compared between groups. RESULTS: Eighteen (25.0%) of the 72 provisional implants
      were prematurely lost. The loss rate of unsplinted implants (37.5%) was
      significantly higher than that of splinted implants (9.3%). Patient handling and
      maintenance of maxillary interim overdentures during the follow-up period was
      found to be easier with the splinted bar-retained method than with the unsplinted
      prosthodontic method. CONCLUSION: Placement of provisional implants fulfilled the
      requirements for initiating immediate prosthetic rehabilitation and showed that
      removable interim overdentures can be adequately stabilized and provide added
      patient comfort and satisfaction. The results suggest benefits of the splinted
      retention modality over the unsplinted method because of advantages regarding
      failure rate, patient handling, and interim denture maintenance.

PMID- 15945305
TI  - Fiber-reinforced composites: effect of fiber position, fiber framework, and
      wetting agent on flexural strength.

PMID- 15945306
TI  - Oral rehabilitation with dental implants in oligodontia patients.
AB  - PURPOSE: The aim of this retrospective report was to evaluate the treatment
      outcome of oral rehabilitation with dental implants in oligodontia patients.
      MATERIALS AND METHODS: Thirteen oligodontia patients treated with dental implants
      were examined clinically and radiographically (follow-up 3 +/- 2 years, range 1
      to 8 years). In addition, patient-mediated concerns of satisfaction, treatment
      experience, and level of impairment of oral functions were assessed with
      questionnaires. RESULTS: In general, all patients were satisfied with the implant
      treatment and experienced the treatment as nonaggravating. There was significant
      functional improvement, with an implant survival rate of 86% and 96% for the
      maxilla and mandible, respectively. CONCLUSION: Dental implants can play an
      important role in the oral rehabilitation of patients with oligodontia. Patients
      were generally satisfied with the overall treatment experience and reported
      significant functional improvement. Implant survival rate was comparable with
      previous reports.

PMID- 15945307
TI  - Variation in blood flow of supporting tissue during use of mandibular complete
      dentures with hard acrylic resin base and soft relining: a preliminary study.
AB  - PURPOSE: This study investigated the influence of hard and resilient polymerized
      acrylic resin base materials on the blood flow of the supporting underlying
      mucosa of mandibular denture wearers during different denture-wearing periods.
      MATERIALS AND METHODS: Measurements were carried out on 20 complete denture
      wearers, 10 with hard bases and 10 with soft ones. The mucosal blood flow
      underlying the dentures was measured bilaterally in the canine and molar regions
      using a laser Doppler flowmeter. Baseline measurements were performed before
      denture wearing and after the dentures were worn for 1 week, 1 month, 3 months,
      and 6 months. RESULTS: Mean blood flow to the mucosa after 1 week was
      significantly lower in the measured regions than that obtained before the
      dentures were worn. Blood flow in the canine region returned to almost normal
      levels 6 months after beginning to wear complete dentures. However, blood flow in
      the molar region of the denture wearers in the hard base group increased after 6
      months, whereas blood flow values did not return to the levels recorded before
      denture insertion in the soft lining group. CONCLUSION: It appears that wearing
      dentures hinders blood flow to denture-supporting tissues, even when soft liners
      are used.

PMID- 15945308
TI  - Three patient reports illustrating the use of dentin adhesives to cement crowns
      to severely worn teeth.
AB  - PURPOSE: Severely worn and broken down teeth present clinical treatment planning
      dilemmas. Extreme examples of worn teeth present in patients suffering from
      bulimia nervosa and dentinogenesis imperfecta. Bulimia nervosa typically presents
      early in adult life with a myriad of clinical features and a most important
      dental sign of eroded palatal surfaces on the maxillary teeth. Dentinogenesis
      imperfecta is a relatively uncommon disorder that presents with varying severity
      of unsupported enamel and results in teeth more susceptible to wear. MATERIALS
      AND METHODS: Dental treatment for both conditions when wear has resulted in the
      complete loss of the tooth can either be directed toward restoring remaining
      tooth tissue or extraction and replacement with implants or dentures. This
      article presents the clinical management of three case histories, each with one
      or more severely broken down teeth, which were restored with adhesively retained
      crowns. RESULTS: Treatment lasted nearly 10 years in one patient and failed after
      6 years in another. The third patient was treated more recently. CONCLUSION: All
      three case histories serve as examples of using adhesive cements to retain
      indirect restorations as a possible prosthodontic management strategy.

PMID- 15945309
TI  - Survival of ceramic computer-aided design/manufacturing crowns bonded to
      preparations with reduced macroretention geometry.
AB  - PURPOSE: Adhesive cementation reduces the need for macroretentive preparation for
      crowns. This study investigated the survival and clinical rating of monolithic
      computer-aided design/manufacturing (CAD/CAM) ceramic crowns bonded to
      preparations with reduced macroretention, hypothesizing that adhesion would
      compensate for reduced retention geometry. MATERIALS AND METHODS: Two-hundred
      eight posterior CAD/CAM-generated crowns from feldspar block ceramic were
      adhesively bonded in 136 patients in three preparation groups: classic (100%
      stump height, n = 70); reduced (reduced stump height or irregular stump, n = 52);
      and endo (absent stump but pulp chamber retention cavity, n = 86). Crowns were
      examined at baseline and after 55 +/- 15 months using modified USPHS criteria.
      Plaque and bleeding of gingiva around the crowns were assessed. RESULTS:
      Cumulative Kaplan-Meier survival of crowns on premolars/molars was: classic =
      97.0%/94.6%; reduced = 92.9%/92.1%; and endo = 68.8%/87.1%, confirming the
      hypothesis for classic, reduced, and endo molars as well as for classic and
      reduced premolars. A significant difference was found between classic and endo
      premolar crowns, rejecting the hypothesis for endo preparation on premolars.
      Plaque and bleeding indices were significantly lower for crowned teeth than for
      controls. CONCLUSION: The survival of classic and reduced crowns was rated
      adequate for premolars and molars. Endo preparation appeared acceptable for molar
      crowns but inadequate for premolar crowns.

PMID- 15945310
TI  - Two-year clinical trial of resin-bonded fixed partial dentures incorporating
      novel attachments.
AB  - PURPOSE: This controlled clinical trial evaluated the clinical performance of a
      new resin-bonded fixed partial denture (FPD) system and compared the clinical
      performance with that of conventional FPDs. MATERIALS AND METHODS: Resin-bonded
      FPDs replaced 12 single anterior and 9 premolar missing teeth in 20 healthy
      patients. Conventional three-unit FPDs (metal-ceramic crowns or complete cast
      metal crowns) replaced 10 single anterior and 10 single posterior missing teeth
      in 20 age-matched controls. Retention, marginal integrity, periodontal condition
      of the FPDs, esthetics and hygiene of pontics, and secondary caries were
      clinically evaluated immediately, 1 month, and 2 years after cementation.
      RESULTS: After 2 years, no failure was observed in the resin-bonded or
      conventional FPDs because of debonding from the abutment teeth. All clinical
      results evaluated for both groups were satisfactory or acceptable. No secondary
      caries was found in either group. Fisher's exact test and/or continuity-corrected
      chi-square test showed no significant differences of satisfactory rates between
      the resin-bonded and conventional FPDs for all variables evaluated. CONCLUSION:
      Short-term clinical results indicate that resin-bonded FPDs may be used as fixed
      prostheses to replace lost single anterior or premolar teeth with minimum
      preparation of abutment teeth. This restoration did not adversely influence
      pulpal or periodontal health. However, a 2-year clinical trial for a new FPD can
      only provide preliminary data, and longer term observations are clearly
      necessary.

PMID- 15945311
TI  - Gender differences in associations between occlusal support and signs of
      temporomandibular disorders: results of the population-based Study of Health in
      Pomerania (SHIP).
AB  - PURPOSE: The aim of this study was to investigate whether gender-dependent
      associations exist between signs of temporomandibular disorders (TMD) and
      occlusal support. MATERIALS AND METHODS: Stratified by gender, the data of 2,963
      35- to 74-year-old participants from the epidemiologic Study of Health in
      Pomerania were used in logistic regression analyses with temporomandibular joint
      (TMJ) tenderness and muscle tenderness as the dependent variables. Occlusal
      support was classified according to the Eichner index, a classification system
      based on occluding pairs of teeth. The final model was adjusted for bruxism, age,
      and various sociodemographic data. RESULTS: Logistic regression analyses revealed
      increased odds ratios for TMJ tenderness in men with loss of all four molar and
      premolar supporting zones (odds ratio 3:9) and without antagonist contact (odds
      ratio 2:7). Significant relationships in men were also found between muscle
      tenderness and loss of one (odds ratio 2:1), three (odds ratio 2:1), or four
      supporting zones (odds ratio 2:7), and loss of any tooth contact (odds ratio
      2:3). In women, significant associations between occlusal support and TMD signs
      were absent. Subjects with bruxism were more likely to have TMJ tenderness (odds
      ratio women 2:0, men 1:9). In women, an additional relationship existed between
      bruxism and muscle tenderness (odds ratio 1:7). The following habits showed no
      significance: gum chewing, unilateral chewing, and lip/tongue/cheek biting.
      CONCLUSION: Only in men was the loss of occlusal support significantly associated
      with muscle and TMJ tenderness. The association between bruxism and TMD signs
      supports the theory that repetitive adverse loading of the masticatory system may
      cause functional disturbances.

PMID- 15945313
TI  - [Pathogenesis of acute coronary syndromes: the activated plaque].
AB  - Atherosclerosis is a chronic disease potentially involving the whole arterial
      system that causes a spectrum of clinical manifestations ranging from acute
      myocardial infarction to stable angina or stroke. The continuous accumulation of
      lipids, and fibrous and inflammatory elements in the arterial wall of the
      coronary tree leads to progressive lumen narrowing with subsequent ischemia and
      symptom-limited exercise. Acute coronary syndromes (unstable angina, acute
      myocardial infarction) have a more complex and dynamic pathogenesis of which
      coronary plaque rupture and thrombosis represent only the final common pathway
      that suddenly compromises resting coronary flow. As only some plaques lead to
      clinical manifestations whereas many others remain asymptomatic, the aim of this
      review was to analyze the complex mechanisms leading to plaque complication and
      rupture with respect to systemic and local features.

PMID- 15945314
TI  - [Acute coronary syndromes in Italy: observations from the BLITZ-2 study].
AB  - The hospital admission of patients with acute coronary syndromes without ST
      segment elevation is increasing in the real world. The aim of the BLITZ-2 study,
      carried out in May 2003, was to investigate the epidemiology and management of
      patients admitted with a diagnosis of non-ST-elevation myocardial infarction. The
      study enrolled 1888 patients with a mean age of 68 years. Among the involved
      hospitals a cath-lab was available in 67.7% in northern Italy vs 37 and 39.8% in
      central and southern Italy, respectively. Only 44 and 55% of patients underwent
      coronary angiography during the first hospital admission in central and southern
      Italy, respectively, against 68% of patients in northern Italy. The type of
      strategy was more influenced by the availability of a cath-lab than by the TIMI
      risk score. A conservative strategy was applied in 45% of patients (26% in
      hospitals with a cath-lab) whereas an invasive approach was used in 55% of
      patients (74% in hospitals with a cath-lab). There was no difference in the TIMI
      risk score between the groups. Age was predictor of coronary angiography: 71% in
      patients < 55 years, 63% in patients 55-74 years, and 44% in patients > or = 75
      years. The in-hospital mortality was 1.2% (1% in northern Italy, 1.4% in central
      Italy, 1.4% in southern Italy) and was higher in high-risk patients (1.5% with
      TIMI risk score > 5) and in older patients (3% in those > or = 75 years). The 1
      month mortality and reinfarction was 2.4 and 3.6%, respectively. The total in
      hospital stay was 8.8 days (coronary care unit stay 3.9 days). The contemporary
      management of Italian patients with acute coronary syndrome turned out to be
      influenced by resource availability, and elderly patients and subjects at higher
      risk are undertreated.

PMID- 15945315
TI  - [Acute coronary syndromes without persistent ST-segment elevation: is risk
      stratification correctly applied?].
AB  - Risk stratification of patients with acute coronary syndromes is of paramount
      importance in achieving maximal benefit from current therapeutic modalities and
      for correct resource allocation. Since risk prediction based on the integration
      of key prognostic variables is relatively inaccurate, the clinical guidelines of
      the European Society of Cardiology (which have been endorsed by the Italian
      Federation of Cardiology) suggest an univariate approach favoring the sensitivity
      of the detection of high-risk patients compromising specificity. Such an approach
      is likely to identify a large population of high-risk patients possibly causing a
      mismatch between the number of patients in need of invasive evaluation and
      treatment, and the availability of interventional resources. Most of the risk of
      adverse cardiac events can be captured by the observation of three prognostic
      indicators: the presence of heart failure, the finding of ST-segment shifts (both
      elevation or depression) in the presenting electrocardiogram, and the elevation
      of markers of myocardial damage. The risk can be even higher in subjects who
      concurrently display additional risk features such as diabetes, renal
      insufficiency, advanced age, or previous revascularization procedures. Such
      patients are likely to be less treated both medically and invasively, than
      patients without such characteristics. The results of Italian regional registries
      show a favorable temporal trend toward a more a aggressive approach in such
      neglected high-risk subgroups.

PMID- 15945316
TI  - [How to administer antithrombotic therapy in non-ST-elevation acute coronary
      syndromes: guidelines and clinical practice].
AB  - It is well known that the role of platelets and the coagulation cascade in the
      pathogenesis of acute coronary syndromes (ACS) without ST-segment elevation and
      the antithrombotic therapy has become the pivotal treatment in these cases. The
      inhibitors of platelet activity (acetylsalicylic acid, thienopyridines,
      glycoprotein IIb/IIIa receptor blockers) and of thrombin activation
      (unfractionated or low-molecular-weight heparin) have gained a growing role in
      the treatment of patients with ACS without ST-segment elevation. According to the
      European Society of Cardiology guidelines, all patients with ACS without ST
      segment elevation should be treated with acetylsalicylic acid, clopidogrel and
      heparin, independently of their risk profile; platelet glycoprotein IIb/IIIa
      receptor inhibitors should be administered intravenously to high-risk patients
      undergoing an invasive procedure (coronary angiography and percutaneous coronary
      intervention or coronary surgery). This review on antithrombotic treatment will
      focus on their correct administration suggested by the European guidelines, and
      will address some peculiar features related to the individual response to each
      drug and to the concomitant administration in selected cases. Acetylsalicylic
      resistance, clopidogrel administration before coronary angiography in high-risk
      patients, dose adjustment in patients with renal failure or low body weight, the
      use of low-molecular-weight heparin in the setting of coronary percutaneous
      intervention, the upstream use of platelet glycoprotein IIb/IIIa receptor
      inhibitors and the patient's wish are also discussed.

PMID- 15945317
TI  - [Coronary revascularization in acute coronary syndrome: which technique? which
      patients? how and when?].
AB  - During the last decades, the prognosis of non-ST-elevation acute coronary
      syndromes has greatly improved. This improvement mainly depends on a better
      understanding of their pathophysiological background that allowed a remarkable
      evolution of their diagnostic and therapeutic management. Likewise, invasive
      strategies have evolved accordingly. Initially, patients with non-ST-elevation
      acute coronary syndromes had a very conservative approach and coronary
      revascularization was strongly discouraged during the acute phase. Afterward, as
      pharmacological therapies and revascularization techniques improved,
      interventional strategies gradually switched to a careful "delayed invasive
      approach". Recently, several studies, taking full advantage from the most
      effective treatments, have demonstrated that an early aggressive strategy
      (coronary revascularization within 48 hours of symptom onset) could reduce the
      incidence of cardiac events in patients with non-ST-elevation acute coronary
      syndromes at medium-to-high risk. These findings made this "early aggressive"
      strategy very attractive. However, in the real world such a strategy is rarely an
      option due to several logistical constraints and very often the selection of the
      therapeutic strategy depends more on resource availability than on patients' risk
      profile. Therefore, Italian cardiologists should pursue integrated healthcare
      models in order to overcome such limitations. They should develop critical
      pathways able to target adequately the patient risk and improve interventional
      networks where even subjects admitted to peripheral hospitals could benefit from
      a timely revascularization procedure according to their risk profile. This could
      reduce treatment disparities and could counteract the vicious circle that tends
      to privilege interventions in low-risk subjects instead of high-risk patients,
      like the elderly, women or diabetics.

PMID- 15945318
TI  - [Management of patients with non-ST-elevation acute coronary syndrome by
      regionalization of care].
AB  - The new guidelines for the treatment of non-ST-elevation acute coronary
      syndromes, recently released by the European Society of Cardiology, state that an
      aggressive approach, that include an early coronary angiography and early
      revascularization whenever anatomically feasible, should be used in every high
      risk patient. However, questions have been raised about the applicability of
      these recommendations in the general population, particularly for patients
      admitted to hospitals where a program of interventional cardiology is not
      available. The most debated and complex features of these guidelines for a
      correct management of acute coronary syndrome in hospitals with and without on
      site catheterization facilities are discussed.

PMID- 15945320
TI  - Stenotrophomonas maltophilia keratitis and scleritis.
AB  - BACKGROUND: Stenotrophomonas maltophilia is a seldom-reported pathogen in ocular
      infections. The report describes six cases of Stenotrophomonas maltophilia (S.
      maltophilia) keratitis and scleritis. To our knowledge, this is the foremost
      report of S. maltophilia scleritis. METHODS: Laboratory reports of patients
      diagnosed with S. maltophilia ocular infections were collected from the
      ophthalmic department of Chang-Gung memorial hospital from January 1, 2000,
      through December 31, 2003. On evaluation of risk factors, isolates, antibiotic
      sensitivities, and response to the treatment ensued. RESULTS: Of the 6 reported
      cases, 5 related bacterial keratitis and 2 scleritis. (One case reported S.
      maltophilia keratitis and secondary scleritis.) The primary risk factor in such
      cases is ocular surgery. The organism cultured was the single isolate in three
      cases (50%). The susceptibility test showed that 50%, 83%, and 100% of the
      isolates were sensitive to ceftazidime, a combination of trimethoprim and
      sulfamethoxazole, and ciprofloxacin respectively. DISCUSSION: Ocular surface
      compromise such as penetrating keratoplasty was a primary risk factor of S.
      maltophilia keratitis in our study. The results of isolates and the antibiotic
      sensitivities were different from previously published results. Our cases
      responded well to antibiotic therapy and antibiotic therapy combined with
      conjunctival autografting. One case of S. maltophilia keratitis and secondary
      scleritis had a poor prognosis, arguably associated with a co-infection of
      Mycobacteria chelonae.

PMID- 15945319
TI  - Deceased-donor liver transplantation: 10 years' experience at Change Gung
      Memorial Hospital-Kaohsiung Medical Center.
AB  - BACKGROUND: The purpose of this study was to summarize the outcomes we achieved
      using deceased-donor liver transplantation (DDLT) in the past 10 years at Chang
      Gung Memorial Hospital-Kaohsiung Medical Center (CGMH-KMC). METHODS: Between
      March 1993 and March 2003, 53 DDLTs were performed at CGMH-KMC. Patients were
      divided into 2 stages: stage 1 (n = 22) from March 1993 to February 1998, and
      stage 2 (n = 31) from March 1998 to March 2003. Indications for transplantation,
      patient demographics, surgical procedures, and long-term outcomes were reviewed.
      RESULTS: Indications for transplantation were biliary atresia (16), post
      hepatitis B/C viral cirrhosis with or without hepatocellular carcinoma (21),
      Wilson's disease (8), primary biliary cirrhosis (3), and miscellaneous (5). Two
      retransplants were carried out for secondary biliary cirrhosis using primary live
      donor liver transplantation (LDLT). Ten patients received grafts from 6 split
      liver transplantations. Over-all Kaplan-Meier 1-, 3-, and 5-year survival rates
      were 88.46%, 83.86%, and 79.87%, respectively. A significant improvement in
      patient survival was observed in stage 2. The Kaplan-Meier 1- and 5-year patient
      survival rates in stage 2 were 96.67% and 92.95%, respectively. Fifteen patients
      developed vascular complications. Nine patients died in this series for an
      overall mortality rate of 17%. CONCLUSIONS: Deceased-donor liver transplantation
      is well established as the treatment of choice for acute and chronic liver
      failure in Taiwan. Satisfactory outcomes have been attained in those transplanted
      to date.

PMID- 15945321
TI  - Choroidal detachment after filtering surgery.
AB  - BACKGROUND: The purpose of this study is to report the treatment and outcome of
      eight cases of choroidal detachment, which occurred several days to many years
      after trabeculectomy. METHODS: This is a retrospective study of eight cases of
      choroidal detachment after trabeculectomy with or without cataract extraction
      reviewed at CGMH, Keelung, from 2002 to 2004. One eye with idiopathic
      scleromalacia with chronic uveitis and secondary glaucoma, five eyes with primary
      open angle glaucoma and two eyes with chronic angle closure glaucoma after
      trabeculectomy were reported. Six of the eight cases developed acute onset
      choroidal detachment within two weeks after surgery. The other two cases suffered
      from choroidal detachment many years after trabeculectomy for different reasons.
      Regarding the types of operation, combined glaucoma and cataract surgery was
      performed in five cases and intraoperative application of adjunctive mitomycin C
      was used in two cases. Decrease in vision acuity and varying degrees of eye pain
      with a flat or shallow chamber were noted in all cases. Associated hypotony was
      found in six of the eight cases. The treatment included topical cycloplegic
      corticosteroid and oral corticosteroid. RESULTS: Choroidal detachments were
      improved or complete resolution obtained after medical treatment for about three
      weeks to one month in all cases. But persistent poor control of intraocular
      pressure was found in two cases. Ultrasonography was used as a reliable tool to
      confirm the diagnosis and resolution of choroidal etachment in cases of blurred
      fundus examination and synechiae miotic pupil. CONCLUSIONS: Choroidal detachment
      is one of the complications after trabeculectomy. The diagnosis of choroidal
      detachment can be confirmed most reliably by ultrasonography. Medical therapy is
      effective for resolution.

PMID- 15945322
TI  - The surgical outcome of strabismus in patients with general fibrosis syndrome.
AB  - BACKGROUND: This study investigates the clinical features of strabismus in
      patients with general fibrosis syndrome (GFS) and the results of surgery
      performed on such patients. METHODS: We conducted a retrospective review of
      patients with GFS who visited our clinic at Chang Gung Memorial Hospital between
      1 August 1992 and 31 January 2002. After evaluating the family histories of 9
      patients with GFS, patients were given a complete ophthalmic evaluation.
      Myectomies of the inferior rectus muscle were performed to correct hypotropia and
      recessions and/or resections of medial rectus and/or lateral rectus were
      performed to correct esotropia or exotropia, respectively. The post-operative
      conditions of the survey patients were reviewed for at least 6 months after the
      completion of the procedures. RESULTS: Six patients (67%) were identified with
      inherited autosomal dominance. All patients displayed the characteristic 'chin
      up' position, limited extraocular muscle movement and eye abnormalities. High
      astigmatism (>=-2.0 diopter) was noted in 9 eyes (50%) and amblyopia was noted in
      all cases. With regard to vertical eye deviation, 11 eyes (61%) were corrected
      through myectomy of the inferior rectus muscle to within 5 degrees as measured
      using a Hirschberg test. Furthermore, three cases (33%) were complicated by lower
      scleral show. CONCLUSION: The presence of GFS complicates the surgical correction
      of strabismus making procedure results more difficult to predict. Strabismus
      surgery has been demonstrated to reduce eye deviation in the primary position,
      thus improving patients' head posture. The resulting improvements to cosmetic
      appearance and functionality lead us to recommend that strabismus surgery be
      performed in conjunction with ptosis surgery for GFS patients.

PMID- 15945323
TI  - Combination of a tension-free vaginal tape procedure and laparoscopic-assisted
      vaginal hysterectomy for the treatment of benign uterine disease associated with
      stress urinary incontinence.
AB  - BACKGROUND: Women undergoing hysterectomy for benign uterine disease (BUD) may
      experience stress urinary incontinence (SUI). We performed tension-free vaginal
      tape (TVT) procedure and laparoscopic-assisted vaginal hysterectomy (LAVH)
      simultaneously and assessed the feasibility and efficacy of TVT performed under
      general anesthesia and the resultant anti-incontinence effects following the
      combined procedures. METHODS: Between March, 2000 and March, 2002 inclusively, 63
      patients, who suffered from both BUD and SUI, underwent LAVH and TVT.
      Preoperative evaluation included history-taking, physical examination and
      ultrasonography. One-hour pad test, multichannel urodynamics and urinary
      questionnaire were conducted preoperatively and postoperatively. Details about
      surgical procedures undertaken, hospitalization and urinary problems in the
      follow-up period were recorded. RESULTS: 50 patients completed the study with a
      mean follow-up period of 34 (25-48) months. The mean age was 49 (39-67) years and
      mean parity 3 (2-6). The mean surgical duration was 163 (95-240) minutes and
      blood loss 284 (100-1,500) milliliters. Mean duration of hospital stay was 5.5
      days and bladder drainage 1.9 days. Three patients suffered bladder perforation
      and one patient was complicated with excess blood loss. Postoperative urinary
      problems included transient urine retention, de novo frequency/urgency symptoms
      and voiding difficultly. CONCLUSIONS: The efficacy of concomitant TVT in LAVH
      procedure remained satisfactory in treatment of SUI associated with BUD. Both
      procedures reflect the benefits of less-invasive surgery. So the combination of
      LAVH and TVT is probably a good alternative for the patient who needs to undergo
      hysterectomy and anti-incontinence surgery simultaneously.

PMID- 15945324
TI  - Intubation conditions with low dose rocuronium under sevoflurane induction for
      children.
AB  - BACKGROUND: During short surgical procedures and when there is a need to avoid
      the use of anticholinesterase at the end of surgery, the use of a smaller
      intubation dose of neuromuscular blocking drug is preferred. The aim of this
      study was to evaluate tracheal intubation conditions using smaller doses of
      rocuronium for children under sevoflurane induction. METHODS: Eighty American
      Society of Anesthesiologists classification physical status I or II children were
      enrolled. After mask induction with sevoflurane with nitrous oxide for 3 minutes,
      0.3 mg/kg of rocuronium was given. Intubation was performed 60 or 90 seconds
      thereafter. Study group A included children aged 1 to 3 years and 90 seconds
      between rocuronium injection and intubation. Group B included children aged 1 to
      3 years who had 60 seconds between rocuronium injection and intubation. Group C
      included children aged 4 to 6 years who had 90 seconds between rocuronium
      injection and intubation. Group D included children aged 4 to 6 years who had 60
      seconds between rocuronium injection and intubation. Intubation conditions were
      judged based on the scoring of ease of jaw opening and laryngoscopy, position of
      the vocal cords, and degree of straining after tracheal intubation. RESULTS: All
      80 children underwent successful tracheal intubation without laryngospasm or any
      complications. Intubation conditions were judged as optimal in all children in
      group A, 95% in group B, 80% in group C, and 65% in group D. CONCLUSIONS: A total
      of 0.3 mg/kg of rocuronium was sufficient for tracheal intubation for children 1
      to 6 years old under sevoflurane induction. To guarantee optimal intubation
      conditions for elder children, allow 90 seconds waiting time after rocuronium
      administration was recommended.

PMID- 15945325
TI  - Ultrasound-guided axillary brachial plexus block in patients with chronic renal
      failure: report of sixteen cases.
AB  - In this report, 16 patients with end-stage renal disease undergoing forearm
      arteriovenous shunt surgery were subjected to an ultrasound-guided axillary
      approach for brachial plexus nerve block. Two doses of 15 ml lidocaine 1.5% were
      injected using a double-shot technique The spread of the solution within the
      plexus sheath could be visualized using a high-resolution 12-MHz imaging probe.
      Most patients (94%) experienced an excellent analgesia in the regions innervated
      by median, ulnar and radial nerves with a lower percentage of complete analgesia
      (63%) in the areas innervated by musculocutaneous nerve. Three patients, who
      complained of pain during the surgery required further supplements of narcotics.
      There were no complications such as, nerve injury, puncture of the axillary
      vessels or other systemic reactions. This technique provides adequate analgesia -
      without complications and without difficulty - for extremity surgery in patients
      with end-stage renal diseases.

PMID- 15945326
TI  - Tracheostomal fire during an elective tracheostomy.
AB  - Some surgeries, a tracheostomy and oral surgeries in particular, have a higher
      risk of fire. Often it can occur when leaking flammable gas contacts an ignition
      heat source. Fire during a tracheostomy can sometimes be seen to produce
      different degrees of insult to the patient. The essential components of a fire,
      i.e., the fuel source, ignition, and an oxidizer, can be avoided or blocked in
      order to prevent fires from occurring. Herein, we discuss a fire during a
      tracheotomy, and ways to avoid its occurrence, and how to stop once it gets
      started. This case demonstrates 2 important points regarding tracheostomies.
      First, extreme caution should be exercised when cautery is used in an
      approximately 100% oxygen gaseous condition, and second, immediate extubation is
      not absolutely necessary if a fire breaks out during a tracheostomy. The
      procedures which can be taken when facing this type of emergency are also
      considered and discussed.

PMID- 15945327
TI  - Anterior megalophthalmos.
AB  - We describe a 36-year-old female who suffered from presenile cataract (nuclear
      sclerosis and posterior subcapsular opacity, with more-severe disease in the
      right eye than in the left) and report the use of some ophthalmologic
      examinations to evaluate the anatomic structures and visual functions of both
      eyes. Slit-lamp biomicroscopy showed increasing horizontal and vertical corneal
      diameters (14.0/13.5 mm) and iridodonesis. The pupils could not be fully dilated,
      and the lenses exhibited cataractous changes. The postlimbal depths were 1.772 mm
      (OD) and 1.690 mm (OS) (normal value, < 0.20 mm). The results of gonioscopy,
      specular microscopy, Goldmann visual field, and intraocular pressure evaluation
      were all within normal limits. Because the patient had bilateral megalocornea in
      the absence of glaucoma, a very deep anterior chamber depth, secondary effects of
      iridodonesis, and changes to cataractous lenses, anterior megalophthalmos was
      diagnosed. This disease is rare. Secondary effects such as iridodonesis, miosis,
      atrophy of the iris stroma lens subluxation, and occurrence of cataractous lens
      should be kept in mind.

PMID- 15945328
TI  - [From prevention to rehabilitation: what is "necessary, useful, superfluous"].

PMID- 15945329
TI  - [Mitral regurgitation: case report].

PMID- 15945330
TI  - [Chronic mitral regurgitation: surgical timing].

PMID- 15945331
TI  - [Aortic valve insufficiency: case report].

PMID- 15945332
TI  - [Aortic valve repair techniques: the "superfluous" turned in "useful" ready to be
      "indispensable"].

PMID- 15945333
TI  - [Conversion of atrial fibrillation to sinus rhythm: when, how, where].

PMID- 15945334
TI  - [Primary dilated cardiomyopathy: case report].

PMID- 15945335
TI  - [What's essential, what's useful and what's superfluous in patients with dilated
      cardiomyopathy].

PMID- 15945336
TI  - [Left ventricular remodeling and prognosis in patients with left ventricular
      dysfunction after bypass surgery].

PMID- 15945337
TI  - [Myocardial infarction: case report].

PMID- 15945338
TI  - [After myocardial revascularization: case report].

PMID- 15945339
TI  - [Beta-blockers in the treatment of heart failure].

PMID- 15945340
TI  - Current therapies for advanced colorectal cancer.
AB  - Significant advances have been made in the treatment of advanced colorectal
      cancer over the past 5 years, namely due to the introduction of three novel
      cytotoxic agents-capecitabine (Xeloda), irinotecan (Camptosar), and oxaliplatin
      (Eloxatin)-and the recent approval of two biologic agents-bevacizumab (Avastin)
      and cetuximab (Erbitux). During this time period, the median survival of patients
      with advanced, metastatic disease has gone from 10 to 12 months to nearly 24
      months. Intense efforts have focused on identifying novel targeted therapies that
      target specific growth factor receptors, critical signal transduction pathways,
      and/or key pathways that mediate the process of angiogenesis. Recent clinical
      trial results suggest that the anti-VEGF antibody bevacizumab can be safely and
      effectively used in combination with each of the active anticancer agents used in
      colorectal cancer. Despite the development of active combination regimens,
      significant improvements in the actual cure rate have not yet been achieved.
      Combination regimens with activity in advanced disease are being evaluated in the
      adjuvant and neoadjuvant settings. The goal is to integrate these targeted
      strategies into standard chemotherapy regimens so as to advance the therapeutic
      options for the treatment of advanced colorectal cancer. Finally, intense efforts
      are attempting to identify the critical molecular biomarkers that can be used to
      predict for either clinical response to chemotherapy and/or targeted therapies
      and/or the drug-specific side effects. The goal of such studies is to facilitate
      the evolution of empiric chemotherapy to individually tailored treatments for
      patients with colorectal cancer.

PMID- 15945341
TI  - Management of advanced colorectal cancer in older patients.
AB  - Many elderly individuals have substantial life expectancy, even in the setting of
      significant illness. There is evidence to indicate that elderly individuals
      derive as much survival benefit as younger patients from standard chemotherapy
      approaches in advanced colorectal cancer. Effective treatments should not be
      withheld from older patients on the basis of age alone. Treatment decisions
      should be based on functional status, presence of comorbidities, and
      consideration of drug-specific toxicities that can be exacerbated in older
      individuals due to decreased functional reserve. Infusional and weekly
      fluorouracil (5-FU) regimens are better tolerated than bolus and monthly
      regimens. Oral capecitabine (Xeloda) reduces the frequency of a number of
      toxicities compared with bolus 5-FU, including stomatitis, a particularly
      debilitating toxicity in many elderly patients. The effectiveness and
      tolerability of oxaliplatin and irinotecan (Camptosar) appear to be similar in
      older and younger patients. Older patients can also receive bevacizumab
      (Avastin), although caution is warranted in those with cardiovascular disease.
      Overall survival in metastatic colorectal cancer improves with the availability
      of multiple effective chemotherapeutic agents. The full range of effective
      therapies in advanced colorectal cancer should be extended to elderly patients.

PMID- 15945342
TI  - Emerging targeted therapies for breast cancer.
AB  - Targeted therapies offer a new approach to breast cancer treatment. Rather than
      eliminating both malignant and normal cells nonspecifically, these so-called
      "rational" therapies exploit second messenger proteins, ligands, and receptors
      that are known to be upregulated in neoplastic cells, or are implicated in cancer
      metastasis. This review will highlight a number of these targets and the
      mechanisms that have been targeted in drug design. We will also describe recently
      completed and currently ongoing clinical trials investigating targeted therapies
      and their potential to augment standard breast cancer therapy.

PMID- 15945343
TI  - Recent progress in management of advanced prostate cancer.
AB  - Androgen-deprivation therapy, usually with combined androgen blockade, is
      standard initial treatment for advanced prostate cancer. With failure of initial
      treatment, as indicated by rising prostate-specific antigen (PSA) levels, second
      line hormonal therapy is usually instituted. Over the past several years, it has
      become increasingly clear that systemic chemotherapy has an important role in
      hormone-refractory disease. Phase II trials have demonstrated high PSA and
      measurable disease response rates with taxane single-agent and combination
      treatments. One recent phase III trial showed that docetaxel (Taxotere)/
      estramustine (Emcyt) significantly improved overall survival, progression-free
      survival, and PSA response rate compared with mitoxantrone (Novantrone) plus
      prednisone. Another phase III trial demonstrated that docetaxel given every 3
      weeks plus prednisone significantly improved overall survival, PSA response rate,
      pain relief response rate, and quality of life compared with mitoxantrone and
      prednisone. On the basis of these findings, every-3-week docetaxel plus
      prednisone is now considered standard first-line therapy for metastatic hormone
      refractory disease. There is considerable optimism that treatment can be further
      improved. Studies of taxane combinations with bevacizumab (Avastin), thalidomide
      (Thalomid), bortezomib (Velcade), antisense Bcl-2 oligonucleotide, mTOR
      inhibitors, epidermal growth factor receptor inhibitors, and KDR inhibitors are
      under way. Randomized phase III trials in progress or planned are examining
      docetaxel in combination with imatinib mesylate (Gleevec) or calcitriol and
      docetaxel/prednisone in combination with bevacizumab and an antisense clusterin
      compound. Other promising systemic agents include epothilones and atrasentan, and
      promising vaccines include Provenge, GVAX, and Prostvac.

PMID- 15945344
TI  - Practical management of chemotherapy-induced nausea and vomiting.
AB  - Approximately 70% to 80% of all patients who receive chemotherapy experience
      nausea and vomiting, which can disrupt their lives in numerous ways. Chemotherapy
      induced nausea and vomiting (CINV) has traditionally been classified according to
      three patterns: acute, delayed, and anticipatory. Additional classifications
      include refractory and breakthrough nausea and vomiting. The mechanisms by which
      chemotherapy causes nausea and vomiting are complex, but the most common is
      thought to be activation of the chemoreceptor trigger zone. An appreciation of
      the risk factors for developing CINV is important when matching antiemetic
      treatment to risk. The emetogenicity of the chemotherapy regimen--generally
      categorized as high, moderate, low, or minimal--greatly affects a patient's risk
      for developing CINV In addition to established and emerging pharmacologic
      approaches to managing CINV, many complementary and integrated modalities may be
      options. Progress in CINV management must include a better understanding of its
      etiology and a focus on prevention. This review will consider the etiology,
      assessment, and treatment of patients with CINV.

PMID- 15945345
TI  - Osteoporosis in breast and prostate cancer survivors.
AB  - Recent advances in treatment modalitiesfor breast and prostate cancer have
      resulted in an increasing number of patients that are cured or that, despite
      residual disease, live long enough to start experiencing complications from
      cancer treatment. Osteoporosis is one such problem that has been increasingly
      identified in cancer patients. Hypogonadism and glucocorticoid use are the two
      major causes of bone loss in these patients. Osteoporosis is characterized by low
      bone mass and abnormal bone microarchitecture, which results in an increased risk
      of fractures. Vertebral body and hip fractures commonly result in a drastic
      change of quality of life as they can result in disabling chronic pain, loss of
      mobility, and loss of independence in performing routine daily activities, as
      well as in increased mortality. In patients with prostate carcinoma, androgen
      deprivation therapy by either treatment with a gonadotropin-releasing hormone
      (GnRH) or bilateral orchiectomy results in increased bone turnover, significant
      bone loss, and increased risk of fractures. Patients with breast cancer are at
      increased risk for estrogen deficiency due to age-related menopause, ovarian
      failure from systemic chemotherapy, or from the use of drugs such as aromatase
      inhibitors and GnRH analogs. Several studies have indicated that the prevalence
      of fractures is higher in breast and prostate cancer patients compared to the
      general population. Therefore, patients at risk for bone loss should have an
      assessment of their bone mineral density so that prevention or therapeutic
      interventions are instituted at an early enough stage to prevent fractures. This
      article will address the characteristics of bone loss observed in breast and
      prostate cancer patients and potential treatments.

PMID- 15945346
TI  - [Achievements in molecular genetics studies of diabetes mellitus].
AB  - Tissue specific insulin receptor knockout mice have been employed to study the
      features of non-insulin-dependent diabetes mellitus (NIDDM) at Research Division,
      Joslin Diabetes Center, Boston, Massachusetts. The muscle insulin receptor
      knockout (MIRKO) mice display muscle insulin resistance but do not develop
      hyperinsulinemia or diabetes. White adipose tissue of MIRKO mice have increased
      the sensitivity to insulin and its glucose uptake is dramatically elevated that
      activates fat accumulation and induces obesity which results from an increase in
      adipocyte number (hyperplasia) of the same size as well as individual cells in
      the control mice. MIRKO mouse adipose tissue increased secretion of adiponectin
      that increases the insulin sensitivity and do not alter the leptin production.
      The liver insulin receptor knockout (LIRKO) mice develop a syndrome like NIDDM
      with hyperinsulinemia and hyperglycemia, decreased liver size and its function
      since insulin is an important liver growth factor but they do not suffer with fat
      accumulation The fat tissue insulin receptor knockout (FIRKO) mice become lean
      with the 50-60% reduction of fat masses. FIRKO mouse remains resistant to obesity
      with age and as a result it has high insulin sensitivity and normal glucose
      tolerance. They eat normal amount of food, increase the longevity of life and
      decrease the mortality. The beta-cell insulin receptor knockout in combination
      with the insulin receptor substrates 1 or 2 or both knockouts mice develop beta
      cell insensitivity to insulin and the insensitivity to the stimulation of insulin
      secretion by glucose. The animals show the alterations of beta-cell growth and
      20% of experimental mice develop II type diabetes. The brain insulin receptor
      knockout (BIRKO) mice are obese and insulin resistant. They have increased
      appetite, hyperinsulinemia, hypertrigliceridemia, and decreased responses of
      neurons to epinephrine. The endothelial cell insulin receptor knockout mice have
      the normal levels of insulin and glucose in the circulation, and the normal or
      decreased blood pressure. They look healthy but have decreased level of the
      vascular endothelial growth factor in blood which may prevent the development of
      retinopathy as NIDDM complication.

PMID- 15945347
TI  - [Biochemical characteristics of the blood red cells in pathological conditions (a
      literature review)].
AB  - Literature data on processes occurring in membranes of blood red cells under
      normal and pathological conditions are revieved.

PMID- 15945348
TI  - [Relationship between structure and function of alpha-fetoprotein: conformational
      status and biological activity].
AB  - Alpha-fetoprotein (AFP) is the major mammalian fetal protein and the recognized
      tumor marker. This review summarizes data on structure and function of AFP with
      emphasis on human AFP, which is intensively investigated. During the last decade
      multiple functionally important sites of human AFP have been revealed or
      predicted by searching of similarity between primary structures of AFP and other
      proteins or their DNA sequences. A number of peptides derived from human AFP have
      been studied by different teams of investigators. These peptides were obtained by
      limited proteolysis of AFP or synthesized using solid phase chemistry. Study of
      biological (physiological) activities of these peptides allows determining
      biologically active sites of alpha-fetoprotein and constructing its structural
      and functional map. Biomodulating properties of these peptides make them a
      potential basis for design of drugs for different purposes including using in
      anticancer therapy. Conformational changes in AFP molecule have been intensively
      studied for the last few years and sufficient conformational mobility of AFP with
      the ability to form molten globule form (MGF) despite its stability in solution
      has been demonstrated. Native molecule of AFP may contain cryptic biologically
      active sites, which are not available for ligand binding. These sites become open
      and available for interaction after changes in conformation of AFP molecule.
      Study of conformational changes of AFP under different conditions allows
      understanding molecular mechanisms of its functioning. This review describes and
      analyses data obtained, mainly, during the last few years on study of
      conformational states of alpha-fetoprotein and relationship between
      conformational changes of AFP and its biological activity. Biochemical,
      biophysical and functional characterislics of some well-studied peptide fragments
      of AFP and their structural and functional mapping are presented.

PMID- 15945349
TI  - [Basic principles of computational chemistry for medical biologists].
AB  - The lecture describes the basic principles of computational chemistry underlying
      the methods of molecular modelling used in bioinformatics area. The basic
      positions, methods of molecular and quantum mechanics and combined approaches are
      considered. This lecture is from theoretical cycle "Bioinformatics and Computer
      Aided Drug Design" for fourth year students of Medico-Biological Department of
      Russian State Medical University (specialty--biochemistry, biophysics and medical
      cybernetics). It can also be advised for all students and post-graduate students
      of medico-biological specialties.

PMID- 15945350
TI  - [Effect of the pharmacological agent hesperadin on breast and prostate tumor
      cultured cells].
AB  - Aurora B, which is important for cell division control, is highly expressed in
      large number of cancer cell lines. Hesperadin, a prototype of a pharmacological
      agent, is a small molecule inhibitor of catalytic activity of Aurora B. In
      present work we investigate effect of Hesperadin on breast--MCF7 and prostate
      adenocarcinoma--PC3, cancer cell lines. After Hesperadin treatment we observe
      stop of cell proliferation due to appearance of multiple mitotic defects caused
      by Aurora B activity reduction and elimination of checkpoint proteins--such as
      hBUBR1 and CENP-E--from kinetochores of mitotic chromosomes.

PMID- 15945351
TI  - [Regulation by opiod peptides of the antioxidant enzyme activity and the
      prostanoid system in myocardium during stress].
AB  - The six hour stress in rats was modeled by the method of O. Desiderato. Cardiac
      damage was estimated by myocardial uptace of radioactive 99Tc-pyrophosphate.
      Intravenous administration of mixed mu and delta opioid receptor agonist, D-
      Ala2, Leu5, Arg6-enkephalin (dalargin), (non-penetrating through the blood brain
      barrier) at a dose of 0.1 mg/kg before stress decreased stress-induced 99Tc
      pyroposphate uptake. Pretreatment with dalargin completely abolished the stress
      induced increase in conjugated dienes and malondialdehyde levels in myocardium
      and prevented a decrease in total lipid soluble antioxidant levels in the heart
      after stress exposure. Stress is accompanied by an increase in activity of
      catalase, glutathione peroxidase, glutathione reductase and a decrease in
      activity of superoxide dismutase (SOD). Pretreatment with dalargin completely
      reversed stress-induced decrease in SOD activity but had minor effect on the
      activity of other antioxidant enzymes. Stress also resulted in an increase in
      myocardial content of thromboxane and a decrease in prostacycline and
      prostaglandin E levels in the heart. Pretreatment with dalargin completely
      eliminated these stress-induced changes in myocardial prostanoid levels. We
      propose that stress-induced heart injury depends on the activation of lipid
      peroxidation processes and changes in the prostanoid levels in the heart.
      Cardioprotective effect of dalargin during stress may be mediated via peripheral
      mu and delta opioid receptor stimulation and an inhibition of lipid peroxidation
      processes through SOD activation and also a recovery, of normal prostanoid levels
      in the heart.

PMID- 15945352
TI  - [Antioxidant enzymes of the rat liver, brain, heart and erythrocytes in ammonia
      intoxication].
AB  - Injection of large amounts of ammonium salts leads to rapid death of animals.
      However, the molecular mechanisms involved in ammonia toxicity remain to be
      clarified. We have tested the effect of toxic dose of ammonium acetate on the
      activities of antioxidant enzymes in rat liver, brain, heart and erythrocytes.
      Acute ammonia intoxication resulted in rapid (within 11 min) decrease in
      superoxide dismutase, catalase and glutathione peroxidase activities in liver and
      brain mitochondria and cytosol and in erythrocytes, but in increase of these
      enzyme activities in heart. Diminished activities of the antioxidant enzymes in
      liver, brain and erythrocytes suggest that the systemic oxidative stress takes
      place, whereas their elevated activities in heart can be the adaptive reaction to
      oxidative stress in hyperammoniemia.

PMID- 15945353
TI  - [Hepatoprotective properties of balm Herbamarin and hydrolysates from marine
      invertebrates in toxic hepatitis and ethanol intoxication].
AB  - Protective properties of a syrup balm "Herbamarin" and food hydrolysates of
      scallop, octopus and crab were investigated using experimental toxic hepatitis
      and ethanol intoxication. Preventive administration of the balm and hydrolysates
      to animals subjected to an intoxications by 40% alcohol and CCl4 normalized
      clinical-diagnostic parameters of liver and blood plasma of experimental animals.

PMID- 15945354
TI  - [Enzymes of purine nucleotide metabolism in assessment of the functional
      competence of the immune system].
AB  - Blood lymphocyte activities of 5'-nucleotidases, adenosine deaminase and AMP
      deaminase have been investigated for evaluation of immune system state of albino
      rats under normal conditions, immobilization stress and effect of radiation.
      Stress-induced reactions were characterized by changes of activities of these
      enzymes. However the ratios of activities 5'- nucleotidase/AMP-deaminase
      (coefficient A) and adenosine-deaminase/AMP-deaminase (coefficient B) were even
      more informative than separate analysis of these enzymes.

PMID- 15945355
TI  - [Albumin redistribution between blood and peritoneal exudate in abdominal
      diseases].
AB  - Albumin concentrations were measured in blood serum (As) and in peritoneal
      exudate (Ae) of patients with peritonitis and acute pancreatitis. As and Ae
      registration during several days revealed strong negative correlation between an
      index, Ae/As, and serum albumin As in 51% of the patients. The absolute value of
      the linear correlation coefficient, r, exceeds 0.7 in each of these patients.
      Moreover, pooled data in this group of patients showed that integral correlation
      coefficient was very high, r approximately equal to 0.94 at p < 0.01. In other
      words, the higher ratio Albumin in exudate/Albumin in serum, the lower albumin
      concentration is in serum. Other patients had either lesser coefficient of the
      negative correlation, between -0.3 and -0.7 (14% of all patients) or very low
      negative or even positive correlation of the index, Ae/As, and serum
      concentration As (35% of all patients). Probable albumin redistribution between
      blood, peritoneal exudate and tissue pool in relation to ratio exudate
      Albumin/serum Albumin is discussed.

PMID- 15945356
TI  - [Amperometric enzyme immunosensor for determination of Klebsiella pneumoniae
      antigen].
AB  - An amperometric enzyme immunosensor for detecting the bacterial antigen
      Klebsiella pneumoniae has been developed. The biosensing part of this analytical
      device consists of cholinesterase and antibodies to Klebsiella pneumoniae co
      immobilized into the cellulose nitrate membrane. The conditions of immunosensor
      functioning (ratio of enzyme and antibodies, substrate concentration, pH of
      working buffer solution) were chosen. The sensor with antibodies in dilution 1:20
      demonstrated the best analytical characteristics. Working concentrations were
      ranged from 1 x 10(-9) to 1 x 10(-3) mg/ml, the detection limit was 5 x 10(-10)
      mg/ml. The cross-reactivity of used antibodies to antigens of bacteria, causing
      similar diseases was evaluated. The conditions of immunosensor reuse by
      regeneration of its biosensing part were chosen. The developed immunosensor was
      probed on blood sera of patients suffering from urea tract diseases.

PMID- 15945357
TI  - [Fluorometric method for determination of keratin SH-groups in human epidermis].
AB  - Simple and highly sensitive fluorometric method for determination of keratin SH
      groups using fluorescein mercuric acetate has been developed. It allows to
      determine amount of SH-groups up to 0.1 nmole/mg of protein in extracts of
      corneal layer of human epidermis.

PMID- 15945358
TI  - Adult immunization disparities: a challenge for the public health/primary care
      partnership.
AB  - Vaccine preventable pneumonias account for 5% of all the years of potential life
      lost (YPLL) attributable to racial and ethnic health disparities. Eliminating
      disparities in influenza and pneumococcal vaccination rates could eliminate many
      of these pneumonia deaths and hospitalizations among at-risk individuals. This
      represents one of the most focused and achievable targets within the broader
      agenda of eliminating racial and ethnic health disparities, which is one of two
      major health goals for the nation outlined in Healthy People 2010. A broad, three
      dimensional conceptual framework guiding a strong public health/primary care
      partnership will be required to achieve this goal.

PMID- 15945359
TI  - Who's getting shots and who's not: racial/ethnic disparities in immunization
      coverage.
AB  - This brief report provides data from the National Health Interview Survey (1989
      2002) and offers commentary on reasons for the racial/ethnic disparities in
      immunization coverage for both influenza and pneumococcal vaccines for persons
      aged > or = 65 years. The findings in this report indicate that, although
      influenza and pneumococcal vaccination rates have increased for non-Hispanic
      Blacks and Hispanics, substantial gaps by race/ethnicity persist. Differences are
      observed even among individuals with similar characteristics (eg, education
      levels, similar numbers of healthcare visits, and similar insurance status) but
      from different ethnic groups. In addition, rates of vaccination for ethnic/racial
      groups have not increased at a sufficient rate to reach the national health
      objective for 2010 (90% of persons aged > 64 years receiving annual influenza
      vaccination and having ever received pneumococcal vaccination). By examining the
      successes of new initiatives such as the READII (Racial Ethnic Adult Disparities
      in Immunization) demonstration projects, researchers hope that progress can be
      made to close these racial/ethnic disparities.

PMID- 15945360
TI  - When insurance is not enough: racial and ethnic disparities in immunizations for
      the Medicare population.
AB  - This review article discusses disparities in immunization rates for beneficiaries
      of the US Medicare program. The review considers: 1) historical and statistical
      information on rates of immunization; 2) goals set forward by the Centers for
      Medicaid and Medicare Services (CMS) to eliminate racial and ethnic health
      disparities related to adult immunization; 3) barriers experienced by Medicare
      beneficiaries in receiving immunizations; 4) barriers experienced by health
      professionals in providing adult immunizations; and 5) CMS efforts to increase
      influenza and pneumococcal immunization rates and to eliminate immunization rate
      disparities among Medicare beneficiaries.

PMID- 15945361
TI  - Race, culture, and trust: why should I take a shot if I'm not sick?
AB  - This three-part panel discussion provides information on: 1) the role religious
      leaders can take in influencing health care, health access, and compliance; 2)
      barriers to equal health care and major gaps in immunizations among Hispanics;
      and 3) population management strategies for public health officials and private
      practice physicians. Citing barriers such as mistrust of government programs,
      socioeconomic conditions, lack of access to preventive healthcare services,
      cultural attitudes, and lack of education about immunizations, the speakers also
      offered solutions to overcome resistance to immunization. Panel members supported
      these strategies and provided techniques to implement the strategy: engaging
      faith-based organizations, improving patient-provider communication; and creating
      public health initiatives to be culturally competent.

PMID- 15945362
TI  - Best-practice models that work: the CDC's Racial and Ethnic Adult Disparities
      Immunization Initiative (READII) Programs.
AB  - In this panel discussion, three health leaders provide information on techniques
      and approaches used to effectively implement the CDC's Racial and Ethnic Adult
      Disparities Immunization Initiative (READII) Programs. Part 1 offers an overview
      of READII and information on early results and program accomplishments. In Part
      2, the Mississippi READII initiative is explored, with insights on how this
      program has served 10,000 African Americans in inner-city Jackson, Mississippi as
      well 23,000 elderly African Americans in 18 rural Delta counties, said to be the
      poorest counties in the nation. The third segment of this presentation explains
      challenges and successes found in San Antonio, Texas where READII efforts focused
      on immunizing the city's elderly Hispanics. Readers will find lessons learned and
      plans for future expansion to use as models when considering implementation of
      immunization programs in local communities.

PMID- 15945363
TI  - Re-engineering the primary care practice to eliminate adult immunization
      disparities.
AB  - Traditional "one-patient-at-a-time," doctor-centered primary care practice models
      do not achieve optimal immunization rates for pneumonia and influenza, in part
      because of time pressures and competing demands from a burgeoning list of
      clinical guidelines. Some widely used quality improvement methods (physician
      education, provider feedback, academic detailing, etc.) have only a modest and
      short-lived impact on improving immunization rates. Evidence is mounting that
      practices can substantially improve immunization rates by changing practice
      systems and processes with standing orders and algorithms, expanded nurse
      decision-making, patient education and incentives, and partnerships with
      community-based pharmacies. Quality-focused, constantly-learning practices that
      cultivate a culture of excellence will be most effective in adopting such
      changes.

PMID- 15945364
TI  - No longer outside the mainstream.

PMID- 15945365
TI  - End-linked amino-modified 50-mer oligonucleotides as RNA profiling probes on
      nylon arrays: comparison to UV cross-linked DNA probes.

PMID- 15945366
TI  - Method for selecting and enriching cells expressing low affinity ligands for cell
      surface receptors.

PMID- 15945367
TI  - Streamlined method for purifying single-stranded DNA from PCR products for
      frequent or high-throughput needs.

PMID- 15945368
TI  - Simplex PCR assay for sex determination in mice.

PMID- 15945369
TI  - Conjugal vectors for cloning, expression, and insertional mutagenesis in gram
      negative bacteria.

PMID- 15945370
TI  - Management and visualization of whole genome shotgun assemblies using SAM.
AB  - We have designed and implemented a system to manage whole genome shotgun
      sequences and whole genome sequence assembly data flow. The Sequence Assembly
      Manager (SAM) consists primarily of a MySQL relational database and Perl
      applications designed to easily manipulate and coordinate the analysis of
      sequence information and to view and report genome assembly progress through its
      Common Gateway Interface (CGI) web interface. The application includes a tool to
      compare sequence assemblies to fingerprint maps that has been used successfully
      to improve and validate both maps and sequence assemblies of the Rhodococcus
      sp.RHAI and Cryptococcus neoformans WM276 genomes.

PMID- 15945371
TI  - Selection of protein epitopes for antibody production.
AB  - Protein functional analysis in the post-genomic era is a huge task that has to be
      approached by different methods in parallel. The use of protein-specific
      antibodies in conjunction with tissue microarrays has proven to be one important
      technology. In this study, we present a strategy for the optimized design of
      protein subfragments for subsequent antibody production. The fragments are
      selected based on a principle of lowest sequence similarity to other human
      proteins, optimally to generate antibodies with high selectivity. Furthermore,
      the fragments should have properties optimized for efficient protein production
      in Escherichia coli. The strategy has been implemented in Bishop, which is a Java
      based software enabling the high-throughput production of protein fragments.
      Bishop allows for the avoidance of certain restriction enzyme sites,
      transmembrane regions, and signal peptides. A Basic Local Alignment Search Tool
      (BLAST) scanning procedure permits the selection of fragments of a selected size
      with a minimal sequence similarity to other proteins. The software and the
      strategy were evaluated on a human test data set and verified to fulfill the
      requested criteria.

PMID- 15945372
TI  - Specific detection of bacillus anthracis using a TaqMan mismatch amplification
      mutation assay.
AB  - Single nucleotide polymorphisms (SNPs) are increasingly recognized as important
      diagnostic markers for the detection and differentiation of Bacillus anthracis.
      The use of SNP markers for identifying B. anthracis DNA in environmental samples
      containing genetically similar bacteria requires the ability to amplify and
      detect DNA with single nucleotide specificity. We designed a TaqMan mismatch
      amplification mutation assay (TaqMAMA) around a SNP in the plcR gene of B.
      anthracis. The assay permits specific, low-level detection (25 fg DNA) of this B.
      anthracis-specific SNP, even in the presence of environmental DNA extracts
      containing a 20,000-fold excess of the alternate allele. We anticipate that the
      ability to selectively amplify and detect low copy number DNAs with single
      nucleotide specificity will represent a valuable tool in the arena of biodefense
      and microbial forensics.

PMID- 15945373
TI  - Improved T-DNA vector for tagging plant promoters via high-throughput luciferase
      screening.
AB  - Transferred DNA (T-DNA) tagging is a powerful tool for tagging and in planta
      characterization of plant genes on a genome-wide scale. An improved promoter
      tagging vector is described here, which contains the codon-optimized luciferase
      (luc+) reporter gene 31 bp from the right border of the T-DNA. Compared to the
      wild-type luciferase gene, this construct provides significantly increased
      reporter gene expression and a 40 times higher tagging frequency. The utility of
      the construct is demonstrated in banana, a tropical monocot species, by screening
      embryogenic cell colonies and regenerated plants with an ultrasensitive charged
      coupled device (CCD) camera. The improved vector resulted in a luciferase
      activation frequency of 2.5% in 19,000 cell colonies screened. Detailed molecular
      analysis of flanking DNA sequences in a tagged line revealed insertion of the
      luciferase tag in a novel gene with near-constitutive expression.

PMID- 15945374
TI  - Separate-component-stabilization system for protein and DNA production without
      the use of antibiotics.
AB  - Plasmid instability is a significant concern in the industrial utilization of
      microorganisms for protein or DNA production. Here we report on the development
      of a new and highly effective stabilization system based on the use of the ccd
      antidote/poison genes. For the first time, we separated the antidote gene from
      the poison gene: localizing the former in the plasmid and integrating the latter
      in the bacterial chromosome. We show that this separate-component-stabilization
      (SCS) strategy: (i) allows for perfect stabilization without the use of
      antibiotics; (ii) increases three to five times the recombinant protein
      production levels; and (iii) does not require any specific modification of the
      protein production process or culture medium. We illustrate that point by using
      the classical T7 promotor (i.e., used in most expression systems). Finally, we
      demonstrate that the SCS system increases by five the yield in DNA production, a
      result especially important for the design and production of gene therapy
      constructs void of any antibiotic resistance gene.

PMID- 15945375
TI  - Validation of oligonucleotide microarray data using microfluidic low-density
      arrays: a new statistical method to normalize real-time RT-PCR data.
AB  - Profiling studies using microarrays to measure messenger RNA (mRNA) expression
      frequently identify long lists of differentially expressed genes. Differential
      expression is often validated using real-time reverse transcription PCR (RT-PCR)
      assays. In conventional real-time RT-PCR assays, expression is normalized to a
      control, or housekeeping gene. However, no single housekeeping gene can be used
      for all studies. We used TaqMan Low-Density Arrays, a medium-throughput method
      for real-time RT-PCR using microfluidics to simultaneously assay the expression
      of 96 genes in nine samples of chronic lymphocytic leukemia (CLL). We developed a
      novel statistical method, based on linear mixed-effects models, to analyze the
      data. This method automatically identifies the genes whose expression does not
      vary significantly over the samples, allowing them to be used to normalize the
      remaining genes. We compared the normalized real-time RT-PCR values with results
      obtained from Affymetrix Hu133A GeneChip oligonucleotide microarrays. We found
      that real-time RT-PCR using TaqMan Low-Density Arrays yielded reproducible
      measurements over seven orders of magnitude. Our model identified numerous genes
      that were expressed at nearly constant levels, including the housekeeping genes
      PGK1, GAPD, GUSB, TFRC, and 18S rRNA. After normalizing to the geometric mean of
      the unvarying genes, the correlation between real-time RT-PCR and microarrays was
      high for genes that were moderately expressed and varied across samples.

PMID- 15945376
TI  - Evaluation of the performance of two carbodiimide-based cyanine dyes for
      detecting changes in mRNA expression with DNA microarrays.
AB  - Microarrays have been extensively used to investigate genome-wide expression
      patterns. Although this technology has been tremendously successful, several
      practical issues would benefit from improvements in design. Here we describe a
      novel, efficient labeling methodology that uses carbodiimide-linked cyanine dyes
      to directly chemically label cDNA derived from mouse total RNA. Using this
      protocol, it takes only 10 min at 70 degrees C to complete the cDNA labeling
      reaction. The directly labeled cDNAs can then be hybridized to 70-mer mouse
      oligonucleotide arrays for expression profiling studies. Microarray analyses
      indicate that these cDNAs are uniformly labeled and produce higher signal
      intensities than conventional enzymatic direct labeling methods and comparable
      signal intensities to those obtained by conventional indirect labeling methods.
      Furthermore, verification of our microarray data using a reverse transcription
      PCR (RT-PCR) method indicates good agreement between the two methods. Thus, we
      conclude that our simplified cyanine-carbodiimide labeling method, which does not
      rely on the incorporation of modified nucleotides, will provide a reliable,
      quicker, and potentially cheaper alternative to established labeling techniques
      for gene expression analyses.

PMID- 15945377
TI  - Canine renal pathology associated with grape or raisin ingestion: 10 cases.
AB  - Ten dogs suffered acute renal failure after ingesting > or = 3 g/kg (dry matter)
      of grapes or raisins. All dogs had degeneration or necrosis (or both) of proximal
      renal tubules with basement membranes remaining intact, and epithelial
      regeneration was observed in 5 out of 10 cases. Mineralized tubular debris or
      granular to proteinaceous casts (or both) were present in all cases. A golden
      brown, globular, intracellular pigment of varying amounts and sizes was observed
      in 6 out of 10 cases with variable reaction with Prussian blue. Multifocal
      fibrinous arteritis of the large colon was seen in 2 out of 5 cases with globulin
      insudation of vessel wall demonstrated by immunohistochemical staining for
      immunoglobulin (Ig)G and IgM. Mineral analysis on frozen renal tissue from 2 out
      of 2 cases revealed mildly elevated Ca:P ratio in both. Clinically significant
      observations were preservation of the integrity of basement membranes after grape
      induced tubular injury and presence of early epithelial regeneration. Thus,
      recovery may be possible if anuria is aggressively managed. With respect to
      potential pathophysiologic mechanisms, further research into the roles of calcium
      homeostasis, vascular reactivity, and the significance of the golden-brown
      pigment is indicated.

PMID- 15945378
TI  - Use of touch-down polymerase chain reaction to enhance the sensitivity of
      Mycobacterium bovis detection.
AB  - The confirmatory diagnosis of Mycobacterium bovis (M. bovis) in animal samples is
      carried out by culture in Stonebrink media. However, culture is very slow because
      of the extremely long duplication time of the bacillus and difficult because of
      the scarcity of bacilli in diagnostic samples. This study describes the
      development of a single-tube touch-down polymerase chain reaction (PCR) protocol
      for the detection of M. bovis using primers that target the IS6110 element.
      Spiked water and milk as well as routine diagnostic samples (milk and nasal
      swabs) from M. bovis-positive cattle were tested. This protocol allows the rapid
      and sensitive detection of M. bovis in bovine samples by enhancing the
      sensitivity of standard PCR amplification.

PMID- 15945379
TI  - Psittacine plasma concentrations of elements: daily fluctuations and clinical
      implications.
AB  - During the past 2 decades, the potential for excessive exposure of pet birds to
      zinc has become a concern for many pet bird owners. Ideally, avian zinc toxicosis
      is diagnosed on the basis of history of exposure to zinc, radiographic evidence
      of ingested metal, occurrence of melena, detection of an elevated plasma zinc
      concentration, and response to treatment. However, most pet birds suspected of
      having zinc toxicosis present with vague signs and lack of radiographic evidence;
      therefore, the diagnosis relies on the presence of an elevated plasma zinc
      concentration. A question was, is there a significant diurnal variation in the
      zinc concentration in psittacine birds and could this be clinically relevant?
      Because studies in other species have shown that zinc is not the only element
      that shows a diurnal variation, the authors examined 13 other plasma elements
      including arsenic, cadmium, calcium, cobalt, copper, iodine, iron, magnesium,
      manganese, molybdenum, potassium, selenium, and total phosphorus. Fifteen adult
      psittacine birds housed in the same aviary were used in this study. Three blood
      samples, separated by 4 hours, were taken from the right jugular vein in each
      bird. All elements were measured in plasma. Zinc, copper, and molybdenum revealed
      diurnal fluctuations. The results of this study suggest that interpretation of
      clinical samples may be more complicated than previously believed. Furthermore,
      on the basis of the results of this study, it is possible that some avian
      reference ranges may need to be reexamined.

PMID- 15945380
TI  - Variation among pathologists in histologic grading of canine cutaneous mast cell
      tumors.
AB  - Ten veterinary pathologists at 1 veterinary institution independently assigned
      histologic grades to the same 60 canine cutaneous mast cell tumors (MCTs). There
      was significant variation among pathologists in grading the MCTs (P < 0.001). The
      probability of assigning a low grade was significantly higher for the
      pathologists in this study who use a published reference for histologic grading
      of canine cutaneous MCTs that allows subcutaneous MCTs or MCTs with mitotic
      figures to be included in the low-grade category (P < 0.0001 and P < 0.0001,
      respectively).

PMID- 15945381
TI  - Novel purification method for recombinant 3AB1 nonstructural protein of foot-and
      mouth disease virus for use in differentiation between infected and vaccinated
      animals.
AB  - An indirect enzyme-linked immunosorbent assay (ELISA) was developed for
      differentiation of animals infected with foot-and-mouth disease virus (FMDV) from
      vaccinated animals. The test was based on a highly pure and concentrated
      preparation of recombinant 3AB1 protein obtained by expression in a prokaryotic
      system, protein separation by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and electro elution. Experimental- and field-serum samples from
      naive, vaccinated, and infected cattle were tested for anti3AB1 antibody using
      the ELISA. A cutoff level was set at 35% of the maximum absorbance obtained with
      a positive control serum (FMDV-infected animal, 21 days postinfection [dpi]).
      This assay could detect antibodies from sera of animals experimentally infected
      by contact (n = 118) with a sensitivity of 97.5%. The specificity was 100%, based
      on negative test results obtained on 109 sera from naive animals. Remarkably, all
      sera from animals vaccinated either once (n = 102) or twice (n = 30) were
      negative. In addition, this 3AB1-ELISA could detect seroconversion at 7 dpi in
      animals inoculated intradermolingually. This assay constitutes an important tool
      for the rapid detection of FMDV outbreaks in a vaccinated population. In
      addition, it presents a reliable, economical, and simple method for testing large
      numbers of serum samples.

PMID- 15945382
TI  - Diagnosis of Taxus (yew) poisoning in a horse.
AB  - A 2-year-old bay Thoroughbred colt was found dead overnight in its stall without
      a known history of any illness, existing disease, or toxicant exposure. No
      information on the clinical signs before this animal's death was reported. A full
      necropsy was performed the next morning and revealed a mild to moderate degree of
      endocardial hemorrhages in both ventricles. Microscopic examination of the heart
      showed an acute mild multifocal necrosis of papillary muscles and ventricles. The
      stomach content contained approximately 2% Taxus alkaloids as determined by gas
      chromatography/mass spectrometry. In the past, diagnosis of Taxus poisoning has
      been mainly based on history of exposure and the presence of plant parts in the
      gastrointestinal tract. Pathological lesions associated with Taxus poisoning have
      not been published for horses. Therefore, this is the first report of cardiac
      lesions in a horse after lethal exposure to Taxus. On the basis of these
      findings, it is suggested that Taxus exposure needs to be considered in the
      differential diagnosis of horses that die suddenly or have cardiac lesions
      suggestive of Taxus exposure, even if intact plant parts are not identified in
      the stomach by the naked eye.

PMID- 15945383
TI  - Pneumatosis cystoides intestinalis in a rabbit doe (Oryctolagus cuniculus).
AB  - Pneumatosis cystoides intestinalis (PCI) is an infrequent condition of animals
      characterized by the existence of numerous thin-walled, gas-filled cystic
      structures within the intestinal wall and adjacent lymph nodes. Microscopically,
      the cystic structures appear to be dilated lymphatics located in the lamina
      propria, submucosa, muscularis, subserosa, mesentery, and mesenteric lymph nodes.
      This report describes a case of pneumatosis cystoides intestinalis in a rabbit
      doe from an organic farm where 20 rabbit does were fed ad libitum with a natural
      diet consisting of whole barley, pea beans, alfalfa hay, and a pelleted vitamin
      mineral blend. A combination of nutritional, bacterial, and other factors are
      hypothesized as possible predisposing factors in the development of PCI.

PMID- 15945384
TI  - A method for detecting complex vertebral malformation in Holstein calves using
      polymerase chain reaction-primer introduced restriction analysis.
AB  - Complex vertebral malformation (CVM), a hereditary lethal disease in Holstein
      calves, is characterized by complex anomalies of the vertebral column and limbs
      in an aborted fetus and in prematurely born, stillborn, and neonatal calves. The
      mode of inheritance of CVM is autosomal recessive, and CVM is caused by a point
      mutation from G to T at nucleotide position 559 of the bovine solute carrier
      family 35 member 3 (SLC35A3) gene. Although an allele-specific polymerase chain
      reaction (AS-PCR) is a useful method for diagnosis of CVM, the AS-PCR requires
      selected DNA polymerases and strictly controlled reaction conditions to obtain
      reliable results. Therefore, an alternative screening method for the CVM gene
      would be useful. Polymerase chain reaction-primer introduced restriction analysis
      (PCR-PIRA) is a method that can be used for detecting a single nucleotide
      mutation in any gene without a restriction site around the mutation site. In this
      study, primers were designed to introduce PstI or EcoT22 sites into PCR products
      from the wild-type and CVM alleles, respectively. The wild-type allele, a
      heterozygote, and a homozygote of the CVM allele could be discriminated by
      restriction fragment length polymorphism analysis. Specific introduction of
      restriction sites into PCR products depending on the change in a single
      nucleotide of template was shown using a variety of DNA polymerases and PCR
      machines. Therefore, the PCR-PIRA technique using primers designed in this study
      might provide a more useful method for extensive screening of CVM.

PMID- 15945385
TI  - Gastrointestinal pythiosis in two cats.
AB  - Two young adult male Domestic Shorthair cats living in the southeastern United
      States were evaluated for signs attributable to partial intestinal obstruction.
      Physical examination indicated a palpable abdominal mass in each animal.
      Exploratory laparotomy revealed a large extraluminal mass involving the ileum and
      mesentery with adjacent mesenteric lymphadenopathy in cat No. 1 and an abscessed
      mass in the distal duodenum in cat No. 2. Mass resection and intestinal
      anastomosis were performed in both cats. Histologic evaluation indicated that the
      intestinal lesions involved primarily the outer smooth muscle layer and serosa
      and consisted of eosinophilic granulomatous inflammation with multifocal areas of
      necrosis. In Gomori methenamine silver-stained sections, broad (2.5-7.5 microm),
      occasionally branching, infrequently septate hyphae were observed within areas of
      necrosis. A diagnosis of Pythium insidiosum infection was confirmed in both cats
      by immunoblot serology and by immunoperoxidase staining of tissue sections using
      a P. insidiosum-specific polyclonal antibody. Cat No. 1 was clinically normal for
      4 months after surgery but then died unexpectedly from an unknown cause. Cat No.
      2 has been clinically normal for at least 9 months after surgery and appears to
      be cured on the basis of follow-up enzyme-linked immunosorbent assay serology.

PMID- 15945386
TI  - Proliferative pododermatitis (canker) with intralesional spirochetes in three
      horses.
AB  - Spirochetes were identified histologically in canker (proliferative
      pododermatitis) in 3 horses. The data suggest that spirochetes may contribute to
      the pathology of equine chronic foot diseases similar to the manner in which they
      contribute to the pathology of bovine papillomatous digital dermatitis and
      contagious ovine digital dermatitis.

PMID- 15945387
TI  - Systemic candidiasis in an apparently immunocompetent dog.
AB  - Members of the family Candida spp. are ubiquitous dimorphic fungi that normally
      inhabit the alimentary, upper respiratory, and genital mucosae of mammals. Cell
      mediated immunity appears to be an important limitation to the pathologic spread
      of these fungi. Prolonged immunosuppression, cytotoxic chemotherapy causing
      neutropenia, diabetes mellitus, long-term glucocorticoid therapy, and prolonged
      antimicrobial therapy have resulted in an increased incidence of both localized
      and disseminated candidiasis. This report describes a systemic Candida spp.
      infection in a dog with no obvious underlying deficiency in host resistance.
      Cytopathology, histopathology, transmission electron microscopy, and
      immunohistochemical staining were used to determine the etiology of the causative
      agent.

PMID- 15945388
TI  - Experimental transmission of chronic wasting disease agent from mule deer to
      cattle by the intracerebral route.
AB  - This communication reports final observations on experimental transmission of
      chronic wasting disease (CWD) from mule deer to cattle by the intracerebral
      route. Thirteen calves were inoculated intracerebrally with brain suspension from
      mule deer naturally affected with CWD. Three other calves were kept as
      uninoculated controls. The experiment was terminated 6 years after inoculation.
      During that time, abnormal prion protein (PrP(res)) was demonstrated in the
      central nervous system (CNS) of 5 cattle by both immunohistochemistry and Western
      blot. However, microscopic lesions suggestive of spongiform encephalopathy (SE)
      in the brains of these PrP(res)-positive animals were subtle in 3 cases and
      absent in 2 cases. Analysis of the gene encoding bovine PRNP revealed
      homozygosity for alleles encoding 6 octapeptide repeats, serine (S) at codon 46,
      and S at codon 146 in all samples. Findings of this study show that although
      PrP(res) amplification occurred after direct inoculation into the brain, none of
      the affected animals had classic histopathologic lesions of SE. Furthermore, only
      38% of the inoculated cattle demonstrated amplification of PrP(res). Although
      intracerebral inoculation is an unnatural route of exposure, this experiment
      shows that CWD transmission in cattle could have long incubation periods (up to 5
      years). This finding suggests that oral exposure of cattle to CWD agent, a more
      natural potential route of exposure, would require not only a much larger dose of
      inoculum but also may not result in amplification of PrP(res) within CNS tissues
      during the normal lifespan of cattle.

PMID- 15945389
TI  - Naturally occurring eastern equine encephalitis in a Hampshire wether.
AB  - Eastern equine encephalitis (EEE) was diagnosed (postmortem) in a sheep with
      clinical signs attributable to a central nervous system disease. The sheep was
      febrile and initially had front limb incoordination, which progressed to
      paralysis of both front and hind limbs during a course of 2 days. The sheep
      maintained an alert attitude with the ability to eat up to the time of
      euthanasia. The only clinical pathologic abnormalities were neutrophilia and
      lymphopenia without appreciable leukocytosis, a moderate hyperglycemia, and an
      elevated creatine kinase. Treatment included hydrotherapy for lowering body
      temperature, intravenous fluids, thiamine hydrochloride, tetanus antitoxin,
      antibiotics, and corticosteroids. The only gross lesion at the time of necropsy
      was a wet glistening surface of the brain (leptomeninges). Microscopically, there
      was severe nonsuppurative meningoencephalitis, poliomyelitis, and
      polyradiculoneuritis with mild multifocal neutrophilic infiltration. The EEE
      virus was isolated from the brain, and subsequent fluorescent antibody testing
      for EEE was positive on cell culture.

PMID- 15945390
TI  - Acute depigmentation of fertile brown eggs in a commercial layer operation.
AB  - Rapid depigmentation of brown eggs is an infrequent but startling event in the
      commercial egg industry that can result in significant economic losses. Loss of
      shell pigment in brown-shelled eggs is caused by various factors. In many cases,
      the exact cause of flock-wide pigment loss remains undetermined. A rapid decline
      in shell pigmentation was observed in 2 flocks of Hyline brown layers. The lack
      of evidence of an infectious disease process suggested a feed or management
      problem. On the basis of a small-scale, "in-house" feeding trial, the feed was
      identified as the cause of depigmentation. Feed analysis by liquid chromatography
      with mass spectrometry confirmed the presence of 4,4'-dinitrocarbanilide, a major
      component of nicarbazin (NCZ). There was no evidence of increased mortality, and
      only a slight but transient drop in the egg production was observed.
      Depigmentation effects were rapidly reversed after replacing the feed with NCZ
      free feed.

PMID- 15945391
TI  - Retroperitoneal perirenal pseudocyst in a Massese breed ram.
AB  - The macroscopic and microscopic features of a retroperitoneal perirenal
      pseudocyst in a 12-month-old ram without impairment of renal function are
      described. In humans and animals, uriniferous pseudocysts may be of traumatic
      origin, resulting from rupture of kidney, renal pelvis, or ureter, or congenital.
      Lymphatic pseudocysts may develop secondary to inflammatory obstruction of the
      hilar lymphatics after perinephritis or renal transplantation. In this case,
      histologic characteristics of the pseudocyst wall were suggestive of development
      from the parietal peritoneal layer encapsulating the kidney. This is the first
      case of retroperitoneal perirenal pseudocyst in a sheep.

PMID- 15945392
TI  - Disseminated liposarcoma in a dog.
AB  - A 9-year-old, female Mongrel dog was presented for posterior hindlimb weakness,
      inability to stand, and pain in the lumbosacral and pelvic regions. Radiography
      revealed a lytic lesion extending from L5 to L6 to the ilium. At necropsy, an 8 x
      2 to 3.2 x 3 cm, irregular, white, firm mass was identified extending from the
      left dorsolateral aspect of the L6 vertebrae to the sacrum, crossing the
      sacroiliac joint to the ilium, and reaching the acetabulum without affecting the
      joint cartilage. Tumor masses were also present bilaterally near the
      costochondral junction of several ribs. White, soft nodules were present in the
      heart, pericardium, lungs, spleen, and kidneys as well. Histologically,
      osteolysis with disruption of the cortical bone and reactive bone with the
      presence of multinucleated osteoclasts was noted. Neoplastic cells consisted of
      variable, small basophilic round cells (SBRC) with very scant cytoplasm, larger
      polygonal cells with abundant eosinophilic cytoplasm, and vacuolated cells
      resembling adipocytes. Within the marrow cavity, vacuolated cells with necrosis
      predominated, whereas in periosteal areas, polygonal and vacuolated cells that
      were mixed with a lower percentage of SBRC were more common. In the lungs and
      heart, SBRC predominated, and in the spleen, polygonal cells were more numerous.
      Tumor cells stained positive for vimentin and S-100 and stained negative for
      CD99, neuron-specific enolase, synaptophysin, chromogranin A, cytokeratins,
      desmin, myoglobin, and actin. This tumor most likely arose from the marrow cavity
      of the L6 and later invaded through the vertebral body into adjacent vertebrae
      and various visceral sites.

PMID- 15945393
TI  - Surveillance of amyloidosis and other diseases at necropsy in captive trumpeter
      swans (Cygnus buccinator).
AB  - The purpose of this study was to characterize the incidence and diagnostic
      features of amyloidosis and other diseases found at necropsy in captive trumpeter
      swans (Cygnus buccinator). A search of Iowa State University's Department of
      Veterinary Pathology and Veterinary Diagnostic Laboratory databases yielded 31
      trumpeter swan (C. buccinator) necropsy cases from captive swans in protected
      habitats. Eleven of the 31 birds had amyloid deposition most commonly in the
      spleen (8 of 11), liver (7 of 11), and kidney (6 of 11) and less often in the
      pancreas (2 of 11) and adrenal gland (2 of 11). Amyloid deposition effaced normal
      tissue with adjacent necrosis and hemorrhage in severe cases. Amyloidosis was
      most often diagnosed in February and March. Other disease diagnoses in the
      trumpeter swans included aspergillosis (5 of 31, 16%); bacterial infection (5 of
      31, 16%); lead toxicosis (3 of 31, 10%); gout (2 of 31, 6%); parasitic infection
      (2 of 31, 6%); vitamin E deficiency (1 of 31, 3%); trauma (1 of 31, 3%); and
      ventricular foreign body (1 of 31, 3%). Histopathologic, toxicologic, and
      microbiologic analyses did not define an etiologic diagnosis in the deaths of 9
      trumpeter swans. In these cases, necropsy lesions included emaciation (5 of 9),
      enteritis (1 of 9), pulmonary hemorrhage (1 of 9), and no lesions (3 of 9). The
      number of trumpeter swan case submissions was greatest in January and February.
      This study provides a reference for veterinary diagnosticians concerning
      incidence and diagnostic features of amyloidosis and other diseases in captive
      trumpeter swans of the midwestern United States.

PMID- 15945394
TI  - Depressurization in military aircraft: rates, rapidity, and health effects for
      1055 incidents.
AB  - INTRODUCTION: Aircraft cabin depressurization is a rare event but one which
      demands attention because of the grave potential for aircrew incapacity in
      flight. The purpose of the current study was to determine rates of
      depressurization incidents for U.S. military aircraft, to examine their causes,
      and to evaluate the medical importance of these incidents. METHODS: The U.S. Navy
      and U.S. Air Force safety center databases were searched for decompression
      incidents during FY1981-FY2003. A total of 1055 incidents were analyzed as to the
      cause, speed of onset, and adverse health effects (hypoxia, barotrauma, DCS, or
      any combination of these). The causes of each incident were identified and
      classified by aircraft type. RESULTS: The number of incidents per airframe varied
      from 1 (in many airframes) to 276 in the T-38. The number of total hours flown
      ranged from 16,332 in the T-6 to 8,101,607 in the C-130. The number of sorties
      flown ranged from 8800 in the B-2 to 3,543,061 in the C-130. Of 35 common
      airframes, 30 showed rates between 0 and 20 incidents per million flying hours.
      Depressurization was "slow" in 83% of incidents. Of the 1055 incidents, only 350
      (33.2%) involved adverse health effects. Hypoxia occurred in 221 incidents, DCS
      in 83, and barotrauma in 71. Only 4 (0.4%) resulted in a fatality. Of the 199
      incidents involving hypoxia, 12 (6%) occurred below 4267 m (14,000 ft).
      CONCLUSION: Most reported military aircraft depressurization incidents are slow
      and do not affect aircrew health. Rates have decreased dramatically since the
      1980s. Still, this study lends support to continuing hypobaric chamber training
      for military pilots.

PMID- 15945395
TI  - Gene expression patterns in bone after 4 days of hind-limb unloading in two
      inbred strains of mice.
AB  - INTRODUCTION: An improved understanding of the interdependence of transcriptional
      and genomic control of bone loss is critical for the design of effective and safe
      countermeasures for osteoporosis in space and on Earth. In an effort to test
      whether molecular pathways modulating the loss of functional weight bearing are
      dependent on genetic makeup, we quantified the differential expression of genes
      critical to the early stages of bone remodeling in two different strains of mice.
      METHODS: Adult (4-mo-old) female BALB/cByJ (BALB) and C3H/HeJ (C3H) mice, strains
      with different sensitivities to unloading, were subjected to hind-limb unloading
      (HLU) or normal cage activities. RNA was extracted from the tibia following 4 d
      of HLU and expression levels were determined. RESULTS: In the BALB mice, HLU
      significantly altered transcriptional levels of osterix (-36%), alkaline
      phosphatase (-36%), osteonectin (-44%), collagen type 1 (-55%), MMP2 (-36%),
      osteocalcin (-68%), and osteopontin (+28%). This expression pattern was highly
      correlated (R2 = 0.75) with altered expression levels in the C3H mice, but the
      magnitude of altered mRNA levels was less than half of those in the BALB mice.
      These strain-specific changes in gene expression were consistent with the
      differential changes in bone formation, as determined in a second group of BALB
      and C3H mice. DISCUSSION AND CONCLUSIONS: These data indicate that genetics may
      influence the absolute changes in gene expression of genes during spaceflight,
      but that the molecular pathways targeted by countermeasures of bone loss may not
      need to be specific to an individual's genetic makeup.

PMID- 15945396
TI  - Tumor growth and immune function in mice during hind-limb unloading.
AB  - INTRODUCTION: Spaceflight is associated with changes in several immune
      parameters. Studies in rodents and humans have shown a decrease in resistance to
      bacterial and viral infections. However, the effect of spaceflight conditions on
      tumor immunity has not been explored. METHODS: The hindlimb unloading (HU) murine
      model of spaceflight was used to assess growth and immune reactivity to the S1
      509a tumor cell line during HU as a model of microgravity. Changes in splenic
      mass of mice in the HU model were compared with mice in orthostatic suspension
      and standard housing controls. Furthermore, the role of host immunity in these
      changes was confirmed using mice with the severe combined immunodeficiency (SCID)
      mutation. RESULTS: Mice in the HU model demonstrated significantly increased
      tumor growth (p < 0.01), greater splenic atrophy, and a significantly diminished
      delayed-type hypersensitivity response to tumor antigens (p < 0.05) compared with
      controls. However, when immunodeficient mice were employed, no difference in
      tumor growth was observed. DISCUSSION: Our findings suggest antitumor immunity is
      inhibited in antiorthostatic suspension. The lack of a difference in mean tumor
      size in SCID mice in antiorthostatic suspension compared with standard housing
      controls supports the concept that HU alters host immunity against the S1 509a
      tumor. Further studies are warrranted to delineate the precise effects of
      spaceflight on host immunity, carcinogenesis, and tumor progression.

PMID- 15945397
TI  - Motion sickness decreases arterial pressure and therefore acceleration tolerance.
AB  - BACKGROUND: Motion sickness is a common aeromedical problem that may occur in
      pilots exposed to increased gravitoinertial load in the head-to-foot direction
      (+Gz). Since motion sickness may affect autonomic nervous functions including
      cardiovascular control, it was hypothesized that it might interfere with
      cardiovascular responses to high +Gz, thereby decreasing G tolerance. METHODS: G
      tolerance and cardiovascular responses to increased G load were studied in nine
      subjects in a centrifuge environment under two conditions. In the motion sickness
      condition, the subject was exposed to a motion sickness provocation (MSP)
      comprising repeated rapid changes in G load in combination with a regimen of head
      movements. In the control condition the subject was exposed to similar cumulative
      G-time stress, but without the MSP. Mean arterial pressure (MAP) was measured. An
      index of peripheral vascular resistance was achieved by measuring the difference
      in skin temperature between the forearm and fingertip (deltaT(forearm
      fingertip)). RESULTS: MSP decreased gradual-onset rate G tolerance from 5.1 +/-
      1.0 G (mean +/- SD) to 4.6 +/- 0.9 G. There was no change in gradual-onset rate G
      tolerance in the control condition. Rapid-onset rate G tolerance was lower in the
      motion sickness (2.9 +/- 0.5 G) than in the control (3.4 +/- 0.3 G) condition.
      MSP reduced MAP by 11 mmHg and deltaT(forearm-fingertip) by 4.2 +/- 4.1 degrees
      C. In the control condition MAP and deltaT(forearm-fingertip) were unaffected.
      CONCLUSIONS: Motion sickness may reduce the arterial pressure response to the
      extent that the capacity of an individual to withstand increased G loads in the
      head-to-foot direction is significantly diminished.

PMID- 15945398
TI  - Altitude decompression sickness susceptibility: influence of anthropometric and
      physiologic variables.
AB  - INTRODUCTION: There is considerable variability in individual susceptibility to
      altitude decompression sickness (DCS). The Air Force Research Laboratory Altitude
      DCS Research Database consists of extensive information on 2980 altitude
      exposures conducted with consistent procedures and endpoint criteria. We used
      this database to quantify the variation in susceptibility and determine if
      anthropometric and/or physiologic variables could be used to predict DCS risk.
      METHODS: There were 240 subjects who participated in at least 4 of 70 exposure
      profiles in which between 5 and 95% of all subjects tested developed DCS
      symptoms. A subject/study ratio (SSR) was calculated by dividing the DCS
      experienced by a subject during all their exposures by the DCS incidence for all
      subjects who participated in the identical exposures. The SSR was used to
      identify the relative susceptibility of subjects for use in analyzing possible
      relationships between DCS susceptibility and the variables of height, weight,
      body mass index, age, percent body fat, and aerobic capacity. RESULTS: The DCS
      incidence was 46.5% during 1879 subject-exposures by subjects exposed at least 4
      times. A significant relationship existed between higher DCS susceptibility and
      the combination of lower aerobic capacity and greater weight (p < 0.05).
      DISCUSSION: Despite a correlation, less than 13% of the variation in DCS
      susceptibility was accounted for by the best combination of variables, weight and
      VO2max. CONCLUSION: Differences in DCS susceptibility cover a wide range and
      appear to be related to some anthropometric and physiologic variables. However,
      there was insufficient correlation to allow prediction of an individual's
      susceptibility.

PMID- 15945399
TI  - Pilot behaviors in the face of adverse weather: A new look at an old problem.
AB  - INTRODUCTION: Weather-related general aviation accidents remain one of the most
      significant causes for concern in aviation safety. Previous studies have
      typically compared accident and non-accident cases. In contrast, the current
      study does not concentrate on occurrence outcome. Instead, the emphasis is on the
      different behaviors that pilots exhibit in the face of adverse weather and, by
      inference, on the decision-making processes that underlie those behaviors.
      METHODS: This study compares three weather-related behaviors that reflect
      different levels of risk: visual flight rules flight into instrument
      meteorological conditions ('VFR into IMC'); precautionary landing; and other
      significant weather avoidance actions. Occurrence data (n=491) were drawn from
      the Australian Transport Safety Bureau database of aviation occurrences, and
      included weather-related accidents, incidents, and 'normal operationsd.' RESULTS:
      There were few significant differences between the three weather-related behavior
      groups in terms of pilot demographics, aircraft characteristics, geographic or
      environmental factors, or absolute flight distances. The pattern of relative
      flight distances (a psychological construct) was markedly different for the three
      groups, with pilots in the weather avoidance group being distinguished by taking
      timely action. DISCUSSION: The relative distance results suggest that the mid
      point of the flight can be a 'psychological turning point' for pilots,
      irrespective of the absolute flight distance involved. Hence, pilots' behavior
      was sometimes influenced by psychological factors not related to any particular
      operational aspect of the flight. The results of the weather avoidance group
      indicate that a safe pilot is a proactive pilot. Dealing with adverse weather is
      not a one-off decision but a continually evolving process. This aspect is
      discussed in terms of the concept of 'mindfulness'.

PMID- 15945400
TI  - Motion-sickness medications for aircrew: impact on psychomotor performance.
AB  - INTRODUCTION: Motion sickness remains a significant problem for aircrew both in
      the flying environment (airsickness) and for aircrew deployed at sea
      (seasickness). While some anti-motion-sickness medications provide reasonable
      efficacy, adverse neurocognitive effects limit their use in military personnel
      engaged in safety-sensitive operational roles such as flying. The purpose of this
      study was to assess the impact on psychomotor performance of promethazine,
      meclizine, and dimenhydrinate and to determine if the addition of pseudoephedrine
      or damphetamine to promethazine would ameliorate its adverse effects. METHODS:
      There were 21 subjects (11 men, 10 women), aged 22-59, who were assessed for
      psychomotor performance on 4 tasks as well as with sleepiness and drug side
      effects questionnaires. Psychomotor testing was conducted prior to, and for 7 h
      after, ingestion of a single dose of each of placebo, promethazine 25 mg,
      meclizine 50 mg, dimenhydrinate 50 mg, promethazine 25 mg plus pseudoephedrine 60
      mg, and promethazine 25 mg plus d-amphetamine 10 mg. RESULTS: Relative to
      placebo, promethazine, meclizine, and promethazine plus pseudoephedrine impaired
      performance on all four tasks [serial reaction time (SRT), logical reasoning
      (LRT), serial subraction (SST), and multitask (MT)]. Dimenhydrinate impaired
      performance on the SRT only. Promethazine plus d-amphetamine did not impair
      performance on any task nor did it result in increased sleepiness. The times to
      recovery of normal performance for SRT with promethazine, meclizine,
      dimenhydrinate, and promethazine plus pseudoephedrine were > 7.25, 7.25, 4.25,
      and 7.25 h, respectively; for LRT were > 7.25, > 7.25, ns, and 7.25 h; for SST
      were > 7.25, > 7.25, ns, and 7.25 h; for MT were 7.25, 7.25, ns, and 7.25 h.
      Recovery times to baseline sleepiness levels for promethazine, meclizine,
      dimenhydrinate, and promethazine plus pseudoephedrine were 7.25, > 7.25, 6.25,
      and > 7.25 h. CONCLUSION: Only promethazine plus d-amphetamine was free from
      impact on psychomotor performance and did not increase sleepiness.

PMID- 15945401
TI  - Phobic fear of flying in aircrews: epidemiological aspects and comorbidity.
AB  - BACKGROUND: Phobic fear of flying may affect aircrew members during any phase of
      their flying careers. Symptoms are beyond voluntary control and may lead patients
      to avoid flying and seek medical advice. METHODS: Of 1101 psychiatric files from
      our institute for 1985-2002, 150 represented cases of fliers who suffered from
      phobic fear of flying. Data collected from those files included assessment of
      fear-evoking situations, type of aircraft, class of aircrew duties, aircraft
      accident history, past medical history, age, and associated psychiatric
      comorbidity. RESULTS: We compared a group of 56 pilots with 94 other aircrew
      members. Results included 143 cases of flight phobia behavior and 7 cases of
      anxiety about parachuting. Flight phobia was less frequent among pilots (37.4%)
      than the other aircrew members (62.6%). We found a history of aircraft accident
      to the patient or an acquaintance in 25% of the cases. Observed comorbid
      psychiatric disorders (54%) consisted of depressive disorders (22%), anxiety
      disorders (16%), and personality disorders (7.4%). Fixed-wing pilots and aircrews
      members had a higher incidence of depression than did rotary-wing pilots and
      crewmembers (p < 0.05). Rotary-wing pilots and crewmembers had a higher rate of
      anxiety disorders (p < 0.05). DISCUSSION: Flight phobia encompasses a wide
      spectrum of clinical origins that may lead pilots or other aircrew members to
      refuse to fly. We recommend a careful psychiatric evaluation and close follow-up
      to adequately diagnose fliers with flight phobic reactions, as well as
      establishing adequate medical and/or psychological treatment.

PMID- 15945402
TI  - Vitamin D supplementation in underway submariners.
AB  - INTRODUCTION: We assessed the efficacy of vitamin D supplementation in
      maintaining normal calcium and bone homeostasis in underway submariners deprived
      of sunlight. METHODS: Serum 25-hydroxycholecalciferol (25(OH)D), 1,25
      dihydroxycholecalciferol (1,25(OH)2D), calcium, parathyroid hormone (PTH),
      phosphate, osteocalcin, bone specific alkaline phosphatase, and urinary levels of
      N-telopeptide were examined in 51 subjects aboard a submarine. These levels were
      obtained prior to a 76-d deployment, before and after a 6-d liberty period
      (deployment day 49 and 55), and on return to homeport. There were 26 subjects who
      received 400-lU of vitamin D daily supplementation, and 25 who received placebo.
      RESULTS: Both groups exhibited significant reductions in 25(OH)D levels in the
      initial submergence (a decrease from 28.3 +/- 15 ng x ml(-1) to 24.1 +/- 10 ng x
      ml(-1) in the experimental group and 26.3 +/- 10 ng x ml(-1) to 20.7 +/- 9 ng x
      ml(-1) in the controls), an increase in 25(OH)D levels not significantly
      different from baseline during the liberty period, and decrements in 25(OH)D on
      repeat submergence (22.8 +/- 10 ng x ml(-1) in experimental and 21.4 +/- 10 ng x
      ml(-1) in controls). Both groups exhibited an increase in post-liberty
      osteocalcin (20.4 +/- 6 ng x ml(-1) to 24.5 +/- 5 ng x ml(-1) for experimental
      and 18.3 +/- 6 to 23.5 +/- 7 ng x ml(-1) for controls), and stable serum calcium
      levels throughout the patrol. CONCLUSIONS: 400-IU daily vitamin D supplementation
      was insufficient in maintaining serum vitamin D levels in underway submariners,
      engendering biochemical evidence of bone resorption and turnover. Six d sunlight
      exposure compensated for 49 d sunlight absence, supporting the enormous capacity
      of UV-B mediated vitamin D production.

PMID- 15945403
TI  - Transmissibility of helicopter vibration in the spines of pilots in flight.
AB  - INTRODUCTION: The high incidence of back pain in helicopter pilots (HP) has been
      attributed to vibration and the in-flight pilot's posture. Helicopter vibration
      has a peak power at frequencies around 5 Hz, which is within the range that the
      human upper body presents resonance frequency. This study investigates the
      transmissibility (TR) of helicopter vibration from the seat to the spine of HP,
      and the seat resultant vibration (RSV). METHODS: We monitored 12 male HP during
      flights lasting 2 h on average. Uniaxial accelerometers measured the vibration at
      the L3 and T1 spinae processes of the pilots, and the helicopter backrest. The
      vibration at the pilot's seat, measured by triaxial accelerometers, was taken as
      the reference for the estimation of transmissibility values (TR) to L3, T1, and
      backrest using the cross-spectral method. TR was considered only for the
      frequency presenting the maximum power along the seat Z acceleration, and RSV was
      calculated according to ISO 2631-1. RESULTS: The TR values found for T1 suggest
      the presence of resonance in the pilot's spine during flight. Most of the HP
      presented TR within the range reported in the literature, but two of them had
      higher values at T1. Five flights showed RSV within the "caution zone" for 4-8 h
      of daily exposure. CONCLUSION: Our findings indicate that cyclic compressive
      force due to helicopter vibration can potentially increase the load imposed on
      the spines of pilots during flight. This might explain the incidence of back pain
      and other injuries to the spines of these professionals.

PMID- 15945404
TI  - Diagnostic categories among 232 military aircrew with musculoskeletal
      disabilities.
AB  - BACKGROUND: Musculoskeletal disabilities are a cause for concern in aircrew as
      they can critically affect return to flying duties. Analysis of the nature and
      cause of musculoskeletal disabilities can provide insight to assist in developing
      preventive and therapeutic intervention programs. METHODS: The Institute of
      Aerospace Medicine (IAM) is responsible for centralized evaluation of military
      and civil aircrew with any musculoskeletal disability. We analyzed
      musculoskeletal disabilities among Indian Air Force aircrew who were evaluated at
      this Institute from 2001-2003. RESULTS: A total of 232 aircrew were evaluated.
      The majority (53.4%, n=124) came from the fighter stream. A large proportion
      (30.2%, n=70) were in the age group 26 to 30 yr with an additional number (25.4%,
      n = 59) in the 31-35 age group. Musculoskeletal injuries affecting the spine
      constituted most (48.2%, n = 121) of the disabilities followed by upper limbs
      (28.2%, n = 71) and lower limbs (19.9%, n=50), respectively. Of the spinal
      disabilities, degenerative disease of the disk was the leading diagnosis (46
      aircrew, 38.0%), followed by fracture of the spine (28.1%, n=35). Road traffic
      accidents accounted for almost a quarter of the injuries (23.3%, n=54).
      DISCUSSION: These findings provide insight into the nature of musculoskeletal
      disabilities among military aircrew. Implications for preventive and therapeutic
      strategies are elaborated. Follow-up studies to understand the characteristics
      associated with each disability have been initiated.

PMID- 15945405
TI  - Blood glucose awareness training helps return insulin-treated aviators to the
      cockpit.
AB  - Insulin-treated diabetes mellitus has traditionally been considered disqualifying
      for aviation duties, the major concern being the risk of hypoglycemia. This
      phenomenon may lead to impaired judgment and even loss of consciousness,
      potentially leading to a mishap. Blood glucose awareness training has been
      advanced as a strategy to avoid hypoglycemia by teaching individuals to use the
      appearance of autonomic and neuroglycopenic symptoms as indicators of decreasing
      blood glucose levels. We present two military aviators with newly diagnosed type
      1 diabetes mellitus who were returned to flying duty in a multicrew aircraft.
      Blood glucose awareness training was used as a tool for the education of these
      aviators regarding the early signs of hypoglycemia in order to avoid development
      of more significant hypoglycemia. These cases attest to the importance of blood
      glucose awareness training in the return of diabetic patients to the cockpit.

PMID- 15945406
TI  - Animal surgery during spaceflight on the Neurolab Shuttle mission.
AB  - INTRODUCTION: A surgical procedure has never been required or performed on a
      human in space. Parabolic microgravity simulations have suggested that surgery
      would be technically feasible during spaceflight. PROCEDURES: Survival surgery
      was performed for the first time on rats during the STS-90 Neurolab Shuttle
      mission. Craniotomy, leg dissection, thoracotomy, laminectomy, and laparotomy
      were performed as a part of physiological investigations. RESULTS: Surgical
      techniques successfully demonstrated in rats during spaceflight included general
      anesthesia, wound closure, wound healing, hemostasis, control of surgical fluids,
      operator restraint, and control of surgical instruments. No decrement in manual
      dexterity was noted by the crew, although operative time was longer compared with
      ground experience due to the need to maintain restraint of surgical supplies and
      instruments. CONCLUSIONS: The demonstration that technically demanding
      dissections could be accomplished successfully in space on rats suggests that
      comparable complex surgical procedures should be feasible on humans, if
      necessary, on future long-duration missions.

PMID- 15945408
TI  - Aviation medicine in the United Kingdom: early years, 1911-1918.
AB  - This is the first of three brief papers that summarize the history of aviation
      medicine in the Royal Air Force. Just as the generals and politicians were slow
      to appreciate the potential of the airplane, so the medical establishment was
      slow in understanding that the flight environment involved medical and
      physiological challenges. This note outlines the development of research to
      support British military aviators up to the formation of the Royal Air Force in
      1918.

PMID- 15945407
TI  - Diagnostic instrumentation aboard ISS: just-in-time training for non-physician
      crewmembers.
AB  - INTRODUCTION: The performance of complex tasks on the International Space Station
      (ISS) requires significant preflight crew training commitments and frequent skill
      and knowledge refreshment. This report documents a recently developed "just-in
      time" training methodology, which integrates preflight hardware familiarization
      and procedure training with an on-orbit CD-ROM-based skill enhancement. This
      "just-in-time" concept was used to support real-time remote expert guidance to
      complete ultrasound examinations using the ISS Human Research Facility (HRF).
      METHODS: An American and Russian ISS crewmember received 2 h of "hands on"
      ultrasound training 8 mo prior to the on-orbit ultrasound exam. A CD-ROM-based
      Onboard Proficiency Enhancement (OPE) interactive multimedia program consisting
      of memory enhancing tutorials, and skill testing exercises, was completed by the
      crewmember 6 d prior to the on-orbit ultrasound exam. The crewmember was then
      remotely guided through a thoracic, vascular, and echocardiographic examination
      by ultrasound imaging experts. RESULTS: Results of the CD-ROM-based OPE session
      were used to modify the instructions during a complete 35-min real-time thoracic,
      cardiac, and carotid/jugular ultrasound study. Following commands from the ground
      based expert, the crewmember acquired all target views and images without
      difficulty. The anatomical content and fidelity of ultrasound video were adequate
      for clinical decision making. CONCLUSIONS: Complex ultrasound experiments with
      expert guidance were performed with high accuracy following limited preflight
      training and multimedia based in-flight review, despite a 2-s communication
      latency. In-flight application of multimedia proficiency enhancement software,
      coupled with real-time remote expert guidance, facilitates the successful
      performance of ultrasound examinations on orbit and may have additional
      terrestrial and space applications.

PMID- 15945409
TI  - You're the flight surgeon. Attention deficit hyperactivity disorder.

PMID- 15945410
TI  - You're the flight surgeon. Post traumatic stress disorder.

PMID- 15945411
TI  - Confused about evidence based nursing practice?

PMID- 15945412
TI  - Giant cell arteritis.
AB  - For ophthalmic nurses, the recognition of patients with possible giant cell
      arteritis along with supportive patient education and care are essential
      ingredients for positive patient outcomes.

PMID- 15945413
TI  - Visual loss as a complication of non-ophthalmic surgery: a review of the
      literature.
AB  - Decreased visual acuity and loss of visual ability are devastating anesthetic and
      surgical complications. The incidence is greater in patients with preexisting
      hypertension, diabetes, sickle cell anemia, renal failure, gastrointestinal
      ulcer, narrow-angle glaucoma, vascular occlusive disease, cardiac disease,
      arteriosclerosis, polycythemia vera, and collagen vascular disorders.
      Precipitating factors for ischemic optic neuropathy include prolonged
      hypotension, anemia, surgery trauma, gastrointestinal bleeding, hemorrhage,
      shock, prone position, direct pressure on the globe, and long operative times.
      Prone and Trendelenburg positions can lead to visual loss related to decreased
      venous return from the head. Visual impairment may result from increased
      intracranial pressure, which contributes to undue pressure on the optic nerve.
      The prone position increases the risk of direct compression injury to the orbit
      and corneal abrasion. Astute attention to positioning is imperative, especially
      with the prone position. At-risk patients should receive transfusion once the
      calculated allowable blood loss has been surpassed Unacceptable hemoglobin and
      hematocrit values should be corrected preoperatively and levels monitored during
      the case to avoid intraoperative anemia in at-risk patients. The blood pressure
      of patients with predisposing diseases should be kept within normal limits. To
      avoid this devastating complication, it is imperative that anesthesia providers
      understand contributing factors and prevention strategies.

PMID- 15945414
TI  - Perioperative pharmacology in cataract surgery.

PMID- 15945415
TI  - Recognizing and managing hypoglycemia.

PMID- 15945416
TI  - Establishing landmarks in peripheral retinal photography.

PMID- 15945417
TI  - [Open letter to the Presidents of the Brussels Universite Libre and the Brussels
      Vrije Universiteit].

PMID- 15945418
TI  - [The Institute of Medical Immunology (IMI), a new research institute of the
      Medical School].

PMID- 15945419
TI  - [Recommendations for the prevention of cardiovascular diseases in clinical
      practice. Belgian Working Group on Prevention of Ccardiovascular Diseases].
AB  - These recommendations are largely based on the Executive Summary of the "European
      Guidelines on Cardiovascular Disease Prevention in Clinical Practice" proposed by
      the "Third Joint Task Force of European and other Societies on Cardiovascular
      Disease Prevention in Clinical Practice". The model used to assess the overall
      risk was adapted for Belgium. Otherwise, very few things were changed from the
      Executive Summary of the European Guidelines.

PMID- 15945420
TI  - [The impact of regular physical activity on physical and mental health: how
      motivate the patient?].
AB  - A sedentary lifestyle is associated with the development of numerous diseases and
      seems to increase in western societies. The influence of a regular physical
      activity in the prevention of cardiovascular diseases, diabetes, obesity,
      cancers, anxious and depressive disturbances is summarized. Potential mechanisms
      of its positive influence are discussed and prescription recommendations are
      made.

PMID- 15945421
TI  - [Head formation in the vertebrates: facts and hypotheses].
AB  - One of the most important features of vertebrates is that, as craniates, they
      have a head. They present some developmental similarities with the
      cephalochordates, which constitute a brother group of the vertebrates. The
      amphioxus has a rudimentary brain vesicle, with a frontal single eye. The
      vertebrates differ by formation of a "new" skull, largely developed from neural
      crest and placodic cells. At the light of common literature, we discuss here a
      possible scenario in which an enlargement of the primary neural induction process
      gives rise to an extension of the forebrain, followed by increased neural crest
      cell migration.

PMID- 15945422
TI  - [Dutasteride (Avodart): a novel 5-alpha reductase inhibitor for treatment of
      benign prostate hypertrophy].
AB  - Dutasteride (Avodart), a novel dual 5-alpha reductase inhibitor is effective for
      the treatment of benign prostate hypertrophy, of more than 30 cc because the
      reduction of the level of dihydrotestosterone. By reducing prostatic volume,
      dutasteride improves moderate to severe symptoms and flow rate. It allows a
      reduction of disease progression by reducing the rate of acute urinary retention
      and need for surgery.

PMID- 15945423
TI  - [Guillain-Barre syndrome and non-Hodgkin's lymphoma. Report of one case and
      review of literature].
AB  - Patients with lymphoma frequently develop neurologic abnormalities mainly due to
      nervous system infiltration but also direct drug toxicity. Moreover Guillain
      Barre syndrome (GBS) remains a possible neuropathy, rarely described in non
      Hodgkin's lymphoma. We describe a case of GBS in a patient with non-Hodgkin's
      high grade lymphoma. A 74-year old man with a newly diagnosed stage I high-grade
      lymphoma (precursor B-cell Burkitt like type according to the R.E.A.L.
      Classification) develop flaccid quadriparesis, 7 days after the end of the third
      course of CHOP treatment. The clinical course and neurological examination were
      consistent with GBS. The patient was in tumoral complete response. Despite
      appropriate treatment and a transfer in a reanimation unit, the patient died 3
      days after the beginning of neurologic symptoms. The low number of cases
      described in the international literature doesn't permit to understand the
      association of this neurologic disease with non-Hodgkin's lymphoma. Collecting
      more data could lead interesting information to know the place of malignant
      hematological disease in the natural history of GBS.

PMID- 15945424
TI  - [Felicien Rops: medicine, doctors, and his diseases (second part)].

PMID- 15945425
TI  - A novel surgical treatment of lumbar disc herniation in patients with long
      standing degenerative disc disease.
AB  - OBJECT: In patients with long-standing lumbar degenerative disc disease (DDD)
      conventional surgical therapy of a herniated disc may worsen back pain due to
      further destabilization of the affected motion segment. In recent years, total
      disc arthroplasty has been introduced to treat DDD while maintaining segmental
      mobility. To the best of the authors' knowledge, this is the first report
      involving lumbar disc herniation and long-standing DDD submitted to combined
      anterior microdiscectomy with sequestrectomy and total-disc arthroplasty.
      METHODS: Fourteen patients with long-standing DDD and a recently herniated disc
      underwent total anterior lumbar microdiscectomy, with removal of the herniated
      disc, and total-disc arthroplasty. There were nine women and five men whose mean
      age was 39.6 years (range 22-56 years) in whom back and leg pain had been present
      for a mean of 75.4 (range 9-360) and 9.4 (range 0.33-36) months, respectively.
      Thirteen patients underwent L5-S1 and one underwent L4-5 surgery. In all cases
      the procedure and the postoperative courses were uneventful. After a mean follow
      up period of 12.5 months (range 3.9-21.1 months), outcome was excellent in 11 and
      good in three patients. CONCLUSIONS: The aforementioned surgical treatment of a
      recently herniated lumbar disc in patients with long-standing DDD yielded very
      favorable early results.

PMID- 15945426
TI  - Anterior cervical discectomy and fusion involving a polyetheretherketone spacer
      and bone morphogenetic protein.
AB  - OBJECT: The authors reviewed clinical and radiographic outcomes in patients who
      had undergone anterior cervical discectomy and fusion (ACDF) involving the
      placement of polyetheretherketone (PEEK) spacers filled with recombinant human
      bone morphogenetic protein (rhBMP)-2. METHODS: Data obtained in 24 cases were
      retrospectively evaluated. The follow-up period ranged from 12 to 16 months (mean
      13 months). Fifteen patients presented with radiculopathy, eight with
      myeloradiculopathy, and one with quadriparesis. Single-level ACDF was performed
      in 12 patients, two-level ACDF in nine, and three-level ACDF in three. Clinical
      outcomes were assessed using Odom criteria, and fusion was assessed by examining
      flexion-extension radiographs and computerized tomography scans in cases in which
      arthrodesis was questionable. Follow-up data were available for 23 patients. One
      patient died of medical complications unrelated to surgery 4 weeks after ACDF.
      Clinical outcomes were rated as good/excellent in 22 patients (95%) and fair in
      one (5%). Solid radiographically documented fusion, with evidence of solid
      bridging bone and no instability on flexion-extension x-ray films, was present in
      all cases. Complications included transient recurrent laryngeal nerve injury in
      one case, transient C-5 paresis in one, cerebrospinal fluid leakage in one, and
      transient dysphagia in two. CONCLUSIONS: Analysis of the results indicated that
      ACDF involving an rhBMP-2-filled PEEK spacer leads to good clinical outcomes (by
      Odum criteria) and solid fusion (even in multilevel cases) while avoiding the
      complications associated with harvesting iliac crest bone grafts.

PMID- 15945427
TI  - Usefulness of neurological examination for diagnosis of the affected level in
      patients with cervical compressive myelopathy: prospective comparative study with
      radiological evaluation.
AB  - OBJECT: Although neurological examination is the key step to reaching a correct
      diagnosis of cervical compressive myelopathy (CCM), the accuracy of diagnosis of
      the affected spinal level for CCM has not yet been tested. METHODS: The authors
      conducted a prospective study to elucidate how accurately the affected
      intervertebral level can be determined and decompressed based on neurological
      examination. Fifty patients who underwent successful decompressive surgery for
      cervical myelopathy caused by single-level disc herniation or spondylosis were
      included in this study (38 men and 12 women, mean age 60 years). Three board
      certified spine surgeons participated in establishing the neurological diagnoses.
      One of the three surgeons made a diagnosis of CCM, and the other two conducted
      the neurological examination including deep tendon reflex, pinprick response,
      muscle weakness, and numbness in the hand only, knowing that the patient had CCM,
      and established the neurological-level diagnosis. A single intervertebral level
      responsible for patient's symptoms was determined concordantly based on magnetic
      resonance imaging and myelography findings by two spine surgeons, and this served
      as the standard. Agreement between neurological and neuroimaging/radiological
      level diagnoses was determined. The rate of agreement between neurological and
      neuroimaging diagnosis was 66%. Among the neurological tests, patient-perceived
      location of numbness in the hands was the most useful for establishing the
      affected level. For the other three tests the agreement rate was lower than 50%
      and thus each individual test may not be reliable for diagnosing the affected
      level. CONCLUSIONS: The results of this study suggested that neurological
      examination in patients with CCM is moderately accurate and reliable for
      determining the neurological level of disease.

PMID- 15945428
TI  - CyberKnife stereotactic radiosurgical treatment of spinal tumors for pain control
      and quality of life.
AB  - OBJECT: The authors conducted a study to assess safety, pain, and quality of life
      (QOL) outcomes following CyberKnife radiosurgical treatment of spinal tumors.
      METHODS: Data obtained in all patients with spinal tumors who underwent
      CyberKnife radiosurgery at Georgetown University Hospital between March 2002 and
      March 2003 were analyzed. Patients underwent examination, visual analog scale
      (VAS) pain assessment, and completed the 12-item Short Form Health Survey (SF-12)
      before treatment and at 1, 3, 6, 8, 12, 18, and 24 months following treatment.
      Fifty-one patients with 72 lesions (58 metastatic and 14 primary) were treated.
      The mean follow-up period was 1 year. Pain was improved, with the mean VAS score
      decreasing significantly from 51.5 to 21.3 at 4 weeks (p < 0.001). This effect on
      pain was durable, with a mean score of 17.5 at 1 year, which was still
      significantly decreased (p = 0.002). Quality of life was maintained throughout
      the study period. After 18 months, physical well-being was 33 (initial score 32;
      p = 0.96) and mental well-being was 43.8 (initial score 44.2; p = 0.97). (The
      mean SF-12 score is 50 +/- 10 [standard deviation].) Adverse effects included
      self-limited dysphagia (three cases), diarrhea (two cases), lethargy (three
      cases), paresthesias (one case), and wound dehiscence (one case). CONCLUSIONS:
      CyberKnife radiosurgery improves pain control and maintains QOL in patients
      treated for spinal tumors. Early adverse events are infrequent and minor. The
      authors await long-term follow-up data to determine late complications and tumor
      control rates.

PMID- 15945429
TI  - Surgical management of metastatic disease of the lumbar spine: experience with
      139 patients.
AB  - OBJECT: The surgical treatment of metastatic spinal tumors is an essential
      component of the comprehensive care of cancer patients. In most large series
      investigators have focused on the treatment of thoracic lesions because 70% of
      cases involve this region. The lumbar spine is less frequently involved (20%
      cases), and it is unclear whether its unique anatomical and biomechanical
      features affect surgery-related outcomes. The authors present a retrospective
      study of a large series of patients with lumbar metastatic lesions, assessing
      neurological and pain outcomes, complications, and survival. METHODS: The authors
      retrospectively reviewed data obtained in 139 patients who underwent 166 surgical
      procedures for lumbar metastatic disease between August 1994 and April 2001. The
      impact of operative approach on outcomes was also analyzed. Among the wide
      variety of metastatic lesions, pain was the most common presenting symptom (96%),
      including local pain, radicular pain, and axial pain due to instability. Patients
      underwent anterior, posterior, and combined approaches depending on the
      anatomical distribution of disease. One month after surgery, complete or partial
      improvement in pain was demonstrated in 94% of the cases. The median survival
      duration for the entire population was 14.8 months. CONCLUSIONS: The surgical
      treatment of metastatic lesions in the lumbar spine improved neurological and
      ambulatory function, significantly reducing axial spinal pain; results were
      comparable with those for other spinal regions. Analysis of results obtained in
      the present study suggests that outcomes are similar when the operative approach
      mirrors the anatomical distribution of disease. When lumbar vertebrectomy is
      necessary, however, anterior approaches minimize blood loss and wound-related
      complications.

PMID- 15945430
TI  - Surgical management of spinal metastases: analysis of prognostic factors during a
      10-year experience.
AB  - OBJECT: Refinement of surgical techniques, especially anterior approaches, for
      the management of spinal metastases has improved patient outcomes, despite the
      fact that a complete analysis of the prognostic factors that would inform patient
      selection has not been undertaken. The authors sought to identify such prognostic
      factors for neurological outcome and life expectancy in patients with spinal
      metastases. METHODS: The authors used Kaplan-Meier techniques, log-rank
      comparisons, and a multivariate model stratified by tumor type to identify
      prognostic factors for duration of ability to walk and survival in patients who
      underwent surgical treatment for spinal metastases during a decade when all
      current treatment options were available. Preoperatively, 53 (87%) of the 61
      patients in the study population suffered neurological symptoms (for example,
      weakness) and 52 (85%) were ambulatory. Postoperatively, 59 (97%) were
      ambulatory. Most patients who survived 6 months (81%) remained ambulatory, as did
      66% of those alive at 1.6 years. The median postoperative survival was 10 months.
      The risk factors for loss of ambulation were preoperative loss of ambulatory
      ability, recurrent or persistent disease after primary radiotherapy of the
      operative site, a procedure other than corpectomy, and tumor type other than
      breast cancer. Prognostic factors for reduced survival were surgical intervention
      extending over two or more spinal segments, recurrent or persistent disease after
      primary radiotherapy involving the operative site, diagnosis other than breast
      cancer, and a cervical spinal procedure. CONCLUSIONS: The results of this
      analysis allowed the authors to create a simple prognostic factor scoring system
      that can be applied to individual patients. The positive experience derived from
      this study supports an expanded role for the surgical treatment of metastatic
      spinal disease.

PMID- 15945431
TI  - Spinal tumors in neurofibromatosis type 2. Is emerging knowledge of genotype
      predictive of natural history?
AB  - OBJECT: The authors conducted a study to examine the incidence, classification,
      and progression of spinal tumors in patients with neurofibromatosis Type 2 (NF2)
      treated at a single center, and to examine relationships with the known
      mutational subtypes of NF2. METHODS: They performed a retrospective review of
      clinical records, neuroimaging studies, and genetic data obtained in 61 patients
      with NF2. Forty-one (67%) of 61 patients harbored one or more spinal tumors.
      Thirty-four patients had undergone serial spinal magnetic resonance imaging
      during a mean follow-up period of 52 months (range 10-103 months; median 53
      months). In 16 patients there were multiple extramedullary tumors smaller than 5
      mm, which did not progress. Fourteen patients harbored at least one
      extramedullary tumor that was greater than 5 mm; of these, radiological
      progression was demonstrated or spinal tumor excision was performed during the
      follow-up period in eight cases (57%). Eleven patients harbored intramedullary
      cord tumors in addition to small and large extramedullary tumors, three (27%) of
      which exhibited radiological progression. In cases in which genotypes were known,
      protein-truncating mutations were significantly more likely to be associated with
      the presence of spinal tumors than in other types (p = 0.03, Fisher exact test).
      No associations between clinical behavior of spinal tumors and genotype, however,
      could be demonstrated. CONCLUSIONS: Spinal tumors in cases involving NF2 are
      heterogeneous in type, distribution, and behavior but larger-size tumors are more
      likely to progress significantly. Intramedullary tumors usually accompany
      multiple extramedullary tumors. In the authors' experience subtyping of the NF2
      mutation has not yet influenced management. Protein-truncating mutations are
      associated with an increased prevalence of spinal tumors.

PMID- 15945432
TI  - Embolization of spinal dural arteriovenous fistulas: importance of occlusion of
      the draining vein.
AB  - OBJECT: The aim of this study was to assess whether glue-induced occlusion of the
      draining vein predicts permanent closure of the fistula following embolization of
      spinal dural arteriovenous fistulas (SDAVFs). METHODS: Between 1994 and 2004, 36
      consecutive patients with an SDAVF were treated at the authors' institution.
      Twelve patients underwent surgery and 24 glue-based embolization. In 12 of 24
      embolization procedures the draining vein was occluded and no recurrence or
      persistent fistula was seen during the follow-up period. In the other 12 patients
      the glue had not reached the draining vein and in eight of these the fistula
      recurred, necessitating additional treatment. CONCLUSIONS: In embolization of
      SDAVFs penetration of the glue into the draining vein predicts permanent closure
      of the fistula. When penetration of the glue into the draining vein can be
      expected, embolization is the preferred treatment option. In other cases surgery
      should be the treatment of choice.

PMID- 15945433
TI  - An anatomical study comparing standard fluoroscopy and virtual fluoroscopy for
      the placement of C1-2 transarticular screws.
AB  - OBJECT: The authors sought to compare radiation exposure, surgical time, and
      accuracy of screw placement when using either standard fluoroscopy or virtual
      fluoroscopy for the placement of C1-2 transarticular screws. METHODS: Twenty-two
      C1-2 transarticular screws were placed in 11 cadavers in a randomized and
      alternating order by using either standard fluoroscopy or virtual fluoroscopy
      (fluoronavigation). The radiation time, procedure time, and accuracy of screw
      placement were recorded and statistically compared. A small but statistically
      significant reduction in fluoroscopy time was noted with the virtual fluoroscopy
      technique but the surgical times were similar between the two techniques. The
      incidence of noncritical and critical breaches (those at risk of causing a
      neurovascular injury) was not significantly different between the two groups.
      Careful analysis of the C1-2 anatomy in these specimens underscored the
      importance of placing the screw path in a maximally dorsal and medial portion of
      the C-2 isthmus to avoid injury to the vertebral artery and to maximize the bone
      purchase of the C-1 lateral mass. CONCLUSIONS: Although virtual fluoroscopy may
      represent a useful tool for transarticular screw placement, it does not supplant
      traditional surgical techniques and does not appear to lower the incidence of
      bone breaches that can occur when performing this demanding procedure.

PMID- 15945434
TI  - Positive feedback loop of interleukin-1beta upregulating production of
      inflammatory mediators in human intervertebral disc cells in vitro.
AB  - OBJECT: Interleukin-1beta (IL-1beta) induces neurological symptoms in
      intervertebral disc herniation (IDH). Recently, the existence of a positive
      feedback loop of IL-1beta, which encourages an inflammatory reaction or
      degeneration in the cells of tendon, has been reported. The authors hypothesized
      that there is a positive feedback loop of IL-1beta in the cells of IDH. METHODS:
      Eight human intervertebral disc specimens were harvested during spinal surgery
      for lumbar disc herniation. The cells were stimulated in serum-free medium with
      or without exogenous IL-1beta. The messenger RNA (mRNA) was extracted for reverse
      transcription polymerase chain reaction (PCR) and real-time PCR to quantify the
      mRNA of endogenous IL-1beta, IL-6, cyclooxygenase-2 (COX-2), and matrix
      metalloproteinases (MMPs). The cells were then stimulated in serum-free medium
      with or without exogenous IL-1beta, and then exogenous IL-1beta was removed.
      After 2, 4, and 6 days, the medium was collected, and enzyme-linked immunosorbent
      assay was used to measure the protein concentration of endogenous IL-1beta. The
      mRNA expressions of endogenous IL-1beta, IL-6, COX-2, and MMPs were increased
      significantly depending on the concentration of exogenous IL-1beta. The protein
      concentration of endogenous IL-1beta was increased over time. CONCLUSIONS: There
      was a positive feedback loop of IL-1beta in the cells of IDH. Furthermore, the
      productions of IL-6, COX-2, MMP-1, and MMP-3 were upregulated as a result of the
      increasing concentration of IL-1beta in a positive feedback loop of IL-1beta. The
      authors concluded that this positive feedback loop of IL-1beta upregulated the
      production of mediators and thus can cause cessation of symptoms in IDH.

PMID- 15945435
TI  - Chondroblastoma of the lumbar spine. Report of two cases and review of the
      literature.
AB  - Chondroblastoma is a benign cartilaginous neoplasm that generally affects the
      appendicular skeleton. Twenty-six cases of spinal chondroblastoma have been
      reported in the past 50 years, only six of which were located in the lumbar
      region. The authors report two cases involving this exceptional location. In both
      patients, low-back pain, in the absence of radicular pain, was the presenting
      symptom. In both cases, plain radiography and computerized tomography scanning
      revealed an osteolytic lesion surrounded by marginal sclerosis. Magnetic
      resonance imaging allowed the authors to study the tumor's local extension.
      Examination of a percutaneous fluoroscopy-guided biopsy sample revealed the
      following typical histological features of chondroblastoma: chondroid tissue,
      focally alternating with cellular areas, and no nuclear atypia or pleomorphism.
      To reduce the risk of local recurrence, vertebrectomy and anterior-posterior
      fusion were performed in both cases. In one case, a structural lumbar scoliosis
      was corrected during the posterior procedure. There was no postoperative
      complication. No recurrence was observed during the 3- to 6-year follow-up
      period. The surgery-related results were deemed successful. Although exceptional,
      the diagnosis of chondroblastoma is possible in lesions involving the lumbar
      spine. Other spinal locations are described in the literature, and frequency of
      recurrence is stressed. A vertebrectomy is advised to reduce the risk of local
      recurrence.

PMID- 15945436
TI  - Postoperative recovery of complete sudden paraplegia due to lumbar schwannoma.
      Case report.
AB  - The authors present a rare case of acute complete paraplegia due to a lumbar
      schwannoma. The clinical presentation, magnetic resonance imaging features, and
      management strategy are discussed. A 29 year-old man presented with acute
      complete paraplegia and bladder and bowel incontinence. He had a history of
      stable back pain and a 4-year history of lower-extremity numbness bilaterally.
      Magnetic resonance imaging revealed an enhancing extraaxial mass filling the
      spinal canal over two segments below the conus medullaris. An L1-3 laminectomy
      was performed and the tumor was completely removed. Pathological evaluation
      showed features characteristic of a schwannoma. The patient regained almost
      complete motor function after 6 months. To the authors' knowledge, this is the
      first reported case of acute complete paraplegia secondary to lumbar schwannoma.
      Possible mechanisms of this occurrence are discussed.

PMID- 15945437
TI  - Diaphragmatic paralysis caused by cervical spondylosis. Case report.
AB  - The authors describe a rare case of diaphragmatic paralysis caused by cervical
      spondylosis. A 64-year-old man presented with dyspnea as well as cervical
      radicular pain and left-sided upper-extremity motor weakness. Chest radiography
      revealed elevation of both sides of the diaphragm. All symptoms were ameliorated
      immediately after cervical laminoplasty, and spirometry revealed improvement of
      ventilatory function 6 months after surgery. Cervical spondylosis should be
      considered a factor that can cause respiratory dysfunction.

PMID- 15945438
TI  - Propriospinal myoclonus due to cervical disc herniation. Case report.
AB  - Propriospinal myoclonus is a rare form of spinal myoclonus. In most cases the
      cause has remained unclear. Secondary propriospinal myoclonus has been described
      secondary to various disorders including trauma, tumor, and infection. Thus far,
      propriospinal myoclonus caused by cervical disc herniation has not been reported.
      In the present report, the authors describe the case of a 53-year-old man who
      presented with radicular symptoms of the right C-6 nerve root and myoclonic
      twitches predominantly affecting the abdominal muscles but spreading to adjacent
      muscles. The spread was triggered and enforced by certain movements. Magnetic
      resonance imaging studies revealed a C-6 nerve root compression at the C5-6 level
      on the right side but no cervical myelopathy. Electromyography studies confirmed
      the diagnosis of propriospinal myoclonus. After discectomy and cage-augmented
      fusion via an anterior approach, the myoclonic movement disorder gradually
      subsided. To the authors' knowledge, this is the first report on successful
      treatment of propriospinal myoclonus by spinal disc surgery.

PMID- 15945439
TI  - Spontaneous spinal subdural hematoma associated with low-molecular-weight
      heparin. Case report.
AB  - Spinal subdural hematomas (SDHs) are a rare cause of cord compression and
      typically occur in the setting of spinal instrumentation or coagulopathy. The
      authors report the first case of a spontaneous spinal SDH occurring in
      conjunction with low-molecular-weight heparin use in a patient with a history of
      spinal radiotherapy.

PMID- 15945440
TI  - Spontaneous intracranial hypotension associated with transdural thoracic
      osteophyte reversed by primary. dural repair. Case report.
AB  - Spontaneous intracranial hypotension (SIH) is an increasingly recognized syndrome
      associated with a specific set of clinical and imaging findings; however,
      determining the site of spinal cerebrospinal fluid (CSF) leakage in these
      patients is often difficult, and indications for surgical intervention need to be
      better defined. The authors report on a 55-year-old woman who presented with
      posture-related headache, disorientation, and memory impairment. Imaging features
      were consistent with SIH. Computerized tomography myelography demonstrated a
      large T2-3 anterior transdural osteophyte associated with a CSF fistula. After an
      unsuccessful trial of conservative therapy, the patient underwent median
      sternotomy, T2-3 discectomy and removal of osteophyte, which allowed adequate
      exposure for primary dural repair. Postoperatively, there was immediate and
      prolonged resolution of all of her symptoms. This case of SIH was caused by
      transdural penetration by an anterior osteophyte and CSF leakage in the upper
      thoracic spine, which was treated effectively by anterior exposure and primary
      dural repair. Aggressive surgical intervention may be required to treat upper
      thoracic CSF leaks refractory to other measures.

PMID- 15945441
TI  - Pathological features including apoptosis in subacute posttraumatic ascending
      myelopathy. Case report and review of the literature.
AB  - Subacute posttraumatic ascending myelopathy (SPAM) is a rare disorder that may
      gradually emerge in the first 1 to 3 weeks after a spinal cord injury and is
      unrelated to syrinx formation or mechanical instability. In addition to several
      theories that have been put forth to explain the origin of this syndrome, the
      authors propose a possible role for apoptosis in the causation and the
      progression of SPAM. They discuss the various theories that have been proposed
      thus far, to place the role of apoptosis in perspective and use their case as an
      illustration.

PMID- 15945443
TI  - [Efficiency of treatment in patients with tuberculosis at the present-day stage].

PMID- 15945442
TI  - Short-term results of microendoscopic posterior decompression for lumbar spinal
      stenosis. Technical note.
AB  - OBJECT: The authors applied the technique of microendoscopic discectomy to
      posterior decompression procedures for lumbar spinal stenosis. The purpose of
      this study was to determine the feasibility of using an endoscopic technique to
      treat lumbar spinal stenosis and to evaluate the clinical and radiographic
      results of microendoscopic posterior decompression (MEPD). METHODS:
      Microendoscopic posterior decompression, which involves a unilateral endoscopic
      approach for bilateral decompression, was performed in 47 patients. Clinical and
      radiographic/neuroimaging results were evaluated during the follow-up period
      (minimum duration 1 year). The clinical results were compared with those of the
      conventional laminotomy. Radiographic instability and the degree of surgical
      invasion of the facet joints were evaluated. In a control a group of 29 patients
      open laminotomy was performed. The clinical outcome was evaluated in 44 patients.
      The mean follow-up duration was 22 months. The mean rate of improvement was 72%
      based on the Japanese Orthopaedic Association score, and good results were
      obtained in 38 patients. Although the rate of morbidity decreased in the MEPD
      group, the incidence of complication was slightly higher. Effective decompression
      was demonstrated in the majority of the patients by using magnetic resonance
      imaging. Radiographic instability appeared in one patient postoperatively, and
      based on computerized tomography scanning, a tendency toward invasion of the
      facet joint on the approach side was noted. CONCLUSIONS: Microendoscopic
      posterior decompression is a minimally invasive procedure and is as useful as
      other conventional procedures in treating lumbar spinal stenosis; however, a few
      technical problems remain to be solved.

PMID- 15945444
TI  - [Methodological approaches to organizing nonspecific prevention of tuberculosis].
AB  - The paper presents the basic sections of the nonspecific prevention of
      tuberculosis. The main objective, tasks, and methods for solving the latter are
      formulated for each section. Emphasis is placed on the social and age groups of
      the population while doing sanitary and educational work. Attention is given to
      that it is necessary to evaluate the efficiency of implementation of educational
      programs, which is important for making amendments when the epidemic situation
      and the population's sanitary education change.

PMID- 15945445
TI  - [Efficiency of treatment of Candida-induced lower respiratory tract lesions in
      patients with pulmonary tuberculosis].
AB  - The paper describes the results of a clinical trial of itraconasole as suspension
      in the treatment of Candida-induced lower respiratory tract lesions in patients
      with pulmonary tuberculosis. The first course of the therapy stopped the growth
      of fungal culture in 34 (68%) patients; after its repeated course, there were 42
      (84%) recovered patients out of 50. After the first course of orangul therapy,
      there was a decrease in the titer of fungal growth in 15 (30%) patients. The
      repeated course of the therapy resulted in fungal eradication in 8 of the 15
      patients, a further decrease in the baseline titer of the fungi was observed in 4
      patients. The treatment was ineffective only in 1 (2%) patient, which was
      associated with the progression of disseminated pulmonary tuberculosisand with
      the presence of the dose-dependent fungal strain C. glabrata.

PMID- 15945446
TI  - [Efficiency of the clinical use of short-term controlled treatment (DOTS) in
      patients with new-onset destructive pulmonary tuberculosis].
AB  - Sixty-six patients with new-onset destructive pulmonary tuberculosis isolating
      Mycobacterium tuberculosis (MBT) received short-term controlled treatment (DOTS)
      and 117 patients were given individual treatment regimens. DOTS treatment could
      be effectively completed in 19.7% of the patients, but following 2 months the
      factors that forced individual treatment regimens to be used occurred in 80.3%.
      The efficacy of individual treatment regimens proved to be much higher than that
      of DOTS. The relationship of the efficiency of treatment to the intensity of
      chemotherapy, the number and sizes of caverns was studied in 250 patients with
      pulmonary tuberculosis. It has been found that it is expedient to use a quadruple
      combination therapy only in patients with small and middle-sized (less than 4 cm
      in diameter) solitary caverns in the lungs. Patients with multiple and large
      caverns should be given at least 5 antituberculous drugs from the beginning of
      the basic course of therapy.

PMID- 15945447
TI  - [Interstitial (lymphogenous) disseminated pulmonary tuberculosis: diagnostic
      capacities of computed tomography].
AB  - Computed tomography (CT) as a priority radiation diagnostic technique for
      interstitial lung diseases was used to examine 35 patients with disseminated
      interstitial lymphogenous tuberculosis (ILT). Individuals having ILT amounted to
      29% of the total number of the patients with disseminated pulmonary tuberculosis.
      The major CT markers of ILT are interstitial diffuse bilateral lesion with the
      reticular or reticulonodular macrostructure. ILT is characterized by its
      lymphogenous origin with involvement of the superficial and peripheral lymphatic
      network, by a productive inflammatory reaction showing no tendency to
      consolidation and cavernization, by none or meager bacterial isolation, by a
      negative or insignificant tuberculin sensitivity, as well as by difficulties in
      the identification of a granulomatous component. In terms of the level of damage
      to the interstitial structures, ILT presented with predominant intralobular
      interstitial lesion as small reticularity in 16% of the patients, with
      predominant intralobular interstitial lesion as large reticularity in 59%, and
      with predominant peribronchovascular interstitial lesion in 25%. The identified
      CT types of ILT are noteworthy for a chemotherapeutic approach and its results
      and for the degree of development of interstitial fibrosis.

PMID- 15945448
TI  - [Polymerase chain reaction in the diagnosis of tuberculosis].

PMID- 15945449
TI  - [Diagnosis of aspiration pneumonia complicated by acute purulent destruction in
      persons having risk factors].
AB  - OBJECTIVE: To analyze the causes of development of aspiration pneumonia (AP)
      complicated by acute purulent pulmonary destruction (APPD) and to optimize
      approaches to its diagnosis, by examining the clinical picture and features of
      its development in patients having risk factors. SUBJECTS AND METHODS: 431
      patients with purulent pulmonary diseases, including 314 (72.8%) patients with
      abscessed pneumonia and 117 (27.2%) with lung abscesses. The aspiration mechanism
      of development of the diseases was established in 96 (22.3%) of the 431 patients.
      The patients' age ranged from 38 to 73 years. There were 87 males and 9 females.
      The episodes of massive aspiration of the contents of the stomach [45 (46.9%)],
      and oropharynx [15 (15.6%] and those of foreign body aspiration [36 (37.5%)] were
      analyzed. RESULTS: The aspiration mechanism of development of the diseases was
      established in 96 (22%) of the 431 patients with APPD, which accounted for 22.3%.
      Alcoholic disease was the underlying background disease in most (89.85%)
      patients, which permits alcoholism to be considered to be one of the major risk
      factors of the aspiration syndrome. Aspiration with the gastric food contents
      from the oral cavity was predominant, which makes it possible to consider
      dysphagia to be one of the most potent predictors of AP. Foreign body aspiration
      was established in 36 patients, among them 17 patients were found to have
      aspiration of fragments of teeth, dental fillings, and dentures. The aspiration
      mechanism of the disease was supported by history data, as established a
      documented episode of aspiration, by clinical, X-ray (esophageal and gastric
      roentgenoscopy and roentgenography) and endoscopic (fibrobronchoscopy,
      esophagogastroscopy) findings, as well as by the conclusions of an ENT
      specialist, a dentist, a neurologist, a narcological psychiatrist. The algorithm
      of the pathogenesis of AP and purulent lung diseases was proposed. CONCLUSION:
      Chronic alcoholism associated with peptic ulcer, chronic gastritis, and hepatic
      lesion (hepatitis/cirrhosis) is the most important predictor of AP and APPD.
      Complex clinical and X-ray examination including fibrobronchoscopy,
      esophagogastroscopy, 24-hour gastric juice pH-metry, and consultations of
      particular specialists are indicated to support the fact of aspiration.

PMID- 15945450
TI  - [Some problems in the study of expired air condensate in respiratory diseases].

PMID- 15945451
TI  - [Role of membranous disorders in the development of bronchial hyperreactivity].
AB  - In 69 patients bronchial asthma of varying severity, the biophysical parameters
      of lymphocytic membranes and their phospholipid spectrum were studied in relation
      to the manifestations of nonspecific hyperreactivity of the bronchial tree.
      Membranous biophysical and structural (physicochemical) impairments were
      ascertained to be one of the major pathogenetic mechanisms determining the
      formation of the clinical, pathophysiological, and pathomorphological
      manifestations of the disease, its severity and persistent course.

PMID- 15945452
TI  - [The nature of endobronchitis in some chronic respiratory diseases in the
      elderly].

PMID- 15945453
TI  - [Some blood indices and the leukocytic index of intoxication in tuberculosis,
      pneumonias, abscesses, and cancer of the lung].
AB  - Examining the values of hemoglobin, red and white blood cells, differential
      count, and leukocytic index of intoxication (LII) in patients with tuberculosis,
      abscesses, pneumonias, and cancer of the lung indicated that in accordance with
      clinical and X-ray findings, LII and the count of lymphocytes reflected the
      degree of patients' health status to the greatest extent. These blood values were
      of the greatest prognostic value. In lung cancer, LII increased only when
      inflammatory and purulent complications occurred. Erythrocyte sedimentation rates
      had a greater tendency to increase in nonspecific processes, which may be
      occasionally of differential diagnostic value.

PMID- 15945454
TI  - [Tuberculosis of respiratory organs: diagnosis and chemotherapy].

PMID- 15945455
TI  - [Novel perspective approaches to the therapy of dyslipidaemias].
AB  - Elevated lipid concentration is an important risk factor of cardiovascular
      diseases. Morbidity and mortality of these diseases are decreased by the
      reduction of lipid levels. Statins have significantly contributed to the
      improvement of cardiovascular diseases therapy and have been the most potent of
      the currently available lipid-modifying therapies so far. Intolerance, possible
      adverse events, and a failure to achieve target lipid levels may limit their use
      in some patients. This is also the reason for the development of new
      hypolipidemics. This paper deals with new potential hypolipidemic drugs which
      influence the fate of cholesterol in the organism from both physiological and
      pharmacological points of view. The new substances, such as cholesterol
      absorption inhibitors, ACAT inhibitors, MTP inhibitors, farnesoid receptor X
      antagonists, and SREBP-SCAP ligands represent the novel agents with potential
      hypolipidemic and anti-atherosclerotic activities.

PMID- 15945456
TI  - [Pre-formulation studies of the H1-antihistamine loratadine for a topical dosage
      form].
AB  - The paper focuses on the formulation of the antihistamine loratadine for
      hydrogels. In the first stage of this study, the evaluated polymer for the
      preparation of hydrogels was Carbopol 980 of concentrations of 0.5, 0.8, and
      1.0%. The paper aimed to determine the optimal concentration of Carbopol 980 in
      hydrogel formulation on the basis of the evaluation of the rheological properties
      and biological availability of loratadine from prepared hydrogels. The results of
      the study show 0.5% hydrogel of Carbopol 980 to be optimal for loratadine from
      the standpoint of topical administration.

PMID- 15945457
TI  - [Antioxidative activity of some over-the-counter plant extracts].
AB  - The recent years again saw increased interest of the public in the use of
      traditional natural remedies, such as plant extracts, for the treatment and
      prevention of diseases. This paper evaluates the antioxidative activity and
      content of phenolic substances of selected plant extracts from medicinal herbs,
      sold as dietary supplements with therapeutic effects. Using the production of 3
      nitrotyrosine as the marker, the effects of extracts on the inhibition of
      peroxynitrite-induced nitration of tyrosine was examined, and the results were
      compared with the ability to extinguish the stable radical 2,2-diphenyl-1
      picrylhydrazyl (DPPH). A linear correlation (r = 0.929) was found between the
      ability to extinguish DPPH and to inhibit tyrosine nitration. The found
      antioxidative activity ranged between values of 0-1702, or 0-1482 micromol of the
      catechine equivalent/100 ml of the extract. The total content of phenolic
      substances oscillated within values of 9.4-268.3 mg of the equivalent of gallic
      acid/100 ml of the extract. The significant linear relationship between
      antioxidative activities (r>0.9) and the total content of phenolic substances
      shows that phenolic substances are the principal group responsible for the
      antioxidative activity of the extracts tested.

PMID- 15945458
TI  - [A study of the properties of compacts from a mixed dry binder on the base of
      alpha-lactose monohydrate and microcrystalline cellulose].
AB  - The paper studies the tensile strength and disintegration time of compacts from
      the mixed dry binder MicroceLac 100. Tensile strength and disintegration time of
      tablets were tested in connection with the following factors: compression force,
      compression rate, addition of magnesium stearate, addition of ascorbic acid, the
      model active principle. The compression forces employed were 5, 6, and 7 kN,
      compression rates, 20 and 40 mm/min, stearate concentration 0, 0.4, and 0.8%,
      ascorbic acid concentration, 25 and 50%. With increasing addition of the
      stearate, the strength of compacts from MicroceLacu 100 was decreased for both
      compression rates, but with a higher rate, in a concentration of 0.4%, the
      decrease in strength was more marked. Disintegration time was increased with
      compression force and the addition of the stearate, but in all cases it was very
      short. Increased addition of ascorbic acid further intensified the decrease in
      the strength of compacts and decreased the disintegration time and the effect of
      the stearate on it. Disintegration time of compacts with ascorbic acid in a
      concentration of 50% did not increase with compression force.

PMID- 15945459
TI  - [Knowledge, attitudes, and behaviour of the population of the Czech Republic to
      self-medication I: Knowledge of and information on drugs].
AB  - A large survey carried out from June to September 2002 in the territory of the
      Czech Republic found and analyzed the knowledge of the population of the Czech
      Republic in relation to self-medication and o-t-c drugs and revealed the main
      problematic areas from the viewpoint of the public. The survey was particularly
      focused on the comprehensibility of information in drug information sheets,
      potential habit-formation, possible misuse and overdose of o-t-c drugs, safety of
      natural remedies, and possible interactions between o-t-c and prescription drugs.
      It is obvious that people continue to be afraid of possible undesirable effects
      of drugs. More than one third of responders consider o-t-c drugs safe from the
      viewpoint of habit-formation, more than 75% of responders are aware of a risk of
      misuse and overdose, 79% of responders view natural drugs as safer than the
      synthetic ones, and 73% of responders are completely sure that there exist
      possible interactions between drugs.

PMID- 15945460
TI  - [Comparison of the consumption of antiepileptic drugs in the Czech Republic,
      Scandinavia, and Australia].
AB  - Long-term trends in utilization of antiepileptic drugs expressed in DDD/TID
      according to the 4th ATC level were studied. Wholesale data recorded from
      statistical yearbooks and the database of the State Institute for Drug Control
      (SUKL) were the source of data. The correlation between trends in the Czech
      Republic (CR) and the other countries was studied. The utilization was expressed
      in DDD/1000 inhabitants and day (DDD/TID). The lowest utilization of
      antiepileptics was in the Czech Republic, while highest in Norway (until 1994)
      and Finland (from 1995). The utilization of barbiturates is decreasing. The
      highest one was in Norway and CR. Hydantoins were the most widely utilized group
      in Australia, Sweden, and CR. Even though their utilization was lower in Finland
      and Norway, they were one of the most widely utilized groups there. The
      utilization of succnimide derivatives was very low and still decreases.
      Benzodiazepins were the most widely utilized group in Finland, until 1995 also in
      Australia, from 1996 in Norway. Their utilization increases. Even though the
      utilization of carboxamide derivatives was lower in CR and Australia, they belong
      to the second most widely utilized group there. Fatty acid derivatives were most
      widely utilized in Australia and Finland. Their utilization is lower, but
      increasing in CR. The utilization of N03AX has been increasing in the recent
      period in all countries. The utilization of antiepileptics in CR follows the
      trends in other countries, but on a lower level of DDD/TID.

PMID- 15945461
TI  - [Solubilization and complexation of the antileukotrienic drug Quinlukast in
      aqueous solutions of cyclodextrins].
AB  - Solubility of the new antileukotrienic drug quinlukast (4-{[4-(2
      quinolylmethoxy)phenyl]sulfanyl}benzoic acid) was determined in water and in
      aqueous solutions of alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD),
      hydroxypropyl-beta-cyclodextrin (HP-beta-CD, average degree of substitution 0.8),
      and methyl-beta-cyclodextrin (M-beta-CD, average degree of substitution 1.8). The
      determined solubility of quinlukast in water was 0.081 +/- 0.008 mmol/l (3.12 +/-
      0.30 mg/100 ml) and only an insignificant increase in quinlukast solubility was
      observed in aqueous solutions of beta-CD. However, three well soluble
      cyclodextrins showed a marked solubilizing effect, in aqueous solutions with a
      moderate cyclodextrin concentration 5 g/100ml, a 12-fold increase in quinlukast
      solubility was observed in the case of M-beta-CD, and a 10-fold increase in the
      case of both HP-beta-CD and alpha-CD. Phase solubility diagrams of quinlukast in
      aqueous solutions of these cyclodextrins (up to 0.05 mol/l) were determined. In
      the cases of M-beta-CD and HP-beta-CD, the solubility diagrams were linear (AL)
      and they corresponded to the formation of a soluble inclusion complex quinlukast 
      cyclodextrin 1:1 with the evaluated stability constants K11 300 +/- 35 l/mol and
      260 +/- 30 l/mol for M-beta-CD and HP-beta-CD, respectively. The phase solubility
      diagram of quinlukast in aqueous solutions of alpha-CD showed a marked positive
      deviation (AP) from linearity, the solubilization efficiency of dilute alpha-CD
      solutions was relatively low but it increased progressively with the increasing
      alpha-CD concentration. In the overall evaluation, the cyclodextrins alpha-CD, HP
      beta-CD and M-beta-CD appeared to be suitable for the quinlukast solubilization
      into aqueous solutions.

PMID- 15945462
TI  - [Xanthium spinosum L.--a phytochemical study].
AB  - The paper deals with the isolation of the constituents of Xanthium spinosum L.
      and the determination of its biological activity (toxicity). The taxon which is
      found also in our flora has not been studied from this aspect yet. The used
      methodology is of a bioassay-guided separation character. The Tubifex tubifex
      test (TT test) served as the basic biological test. From the methanol extract of
      the aerial part, ent-kaurane diterpene atractyloside was isolated, from the
      acetone extract of the aerial part, xanthumin and deacetylxanthumin, two
      derivatives of xanthanolides--sesquiterpene lactones, were isolated, and from the
      ethanol extract, phytosterols--beta-sitosterol and stigmasterol. From the acetone
      extract of fruits, fatty acids were obtained.

PMID- 15945463
TI  - [Optimization of isolation of inulin from Cichorium intybus L. and some of its
      uses in social practice].
AB  - The study is concerned with the technological processing of chicory Cichorium
      intybus in order to isolate the fructan polysaccharide inulin (C6H10O5) and the
      optimization of the individual production steps of extraction (the method of
      purification of the raw material prior to the extraction itself and purification
      of the final product. temperature of the extraction mixture, exposure period of
      the extraction agent, effect of pH, optimization of the module for the
      determination of the most suitable volume of the extraction agent, determination
      of the most suitable ratio of the volume of ethanol in the extraction of inulin
      from the reaction medium). The obtained experimental results are compared and
      evaluated with regard to quality (whiteness) and the yield of the obtained final
      product. The paper is also concerned with several possible uses of inulin in
      pharmaceutical, medical, cosmetological, food industrial, and fodder production
      fields.

PMID- 15945464
TI  - [Effect of vanadyl sulfate (VOSO4) on the production of flavonoids by the culture
      Ononis arvensis L. in vitro].
AB  - The study tested the effect of vanadyl (IV) sulfate (VOSO4) on the production of
      flavonoids in the callus and suspension culture of Ononis anrensis L. (Fabaceae).
      This substance proved to be a good abiotic elicitor for an increase in the
      production of secondary substances (flavonoids) in the culture of Ononis arvensis
      L. in vitro. The maximal increase in the formation of flavonoids took place in
      the callus culture after 24-hour elicitation with VOSO4 in a concentration of
      1.227 .10-4 mol/l by 313% in comparison with the control and in the suspension
      culture in a concentration of 1.227 .10-6 mol/l after 48-hour action of the
      elicitor by 485% in comparison with the control.

PMID- 15945465
TI  - Magnetic resonance imaging systems. A guide to the technology.
AB  - Magnetic resonance imaging (MRI) has become firmly established as an essential
      imaging tool. Two characteristics of MRI--its ability to image soft tissue and
      its avoidance of harmful ionizing radiation--more than compensate for the costs,
      complexity, safety issues, and patient discomfort associated with it. Today, MRI
      is the modality of choice for a number of neurological and musculoskeletal
      indications and is being used for more applications than ever before. In some
      cases, MRI is supplementing existing techniques, such as vascular and cardiac
      imaging, while in others it is used to image physiologic processes that are
      invisible to any other imaging modality. MRI scanners are growing increasingly
      complex. As the technology develops, capabilities that were once available only
      to researchers are becoming routine in clinical applications. As a result, buyers
      now have more decisions to make when selecting a scanner than ever before. It is
      no longer simply a choice of field strength or whether to opt for an open or
      closed system. To gain an understanding of the important factors to consider when
      selecting MRI equipment, it is necessary to have a good understanding of how the
      systems work. In this article, we describe the operating principles of MRI
      systems. We also describe the major components of a system and the considerations
      involved when implementing MR imaging. Finally, we describe the issues
      surrounding the higher-powered three-tesla systems that are beginning to see
      commercial use.

PMID- 15945466
TI  - Safety feature on Liebel-Flarsheim CT injector could be disabled, risking
      embolus.

PMID- 15945467
TI  - New reports of caster failures raise concerns about the safety of Medi-Mech
      carts.

PMID- 15945468
TI  - Leaky damping chamber on Datex-Ohmeda monitors can prevent blood pressure
      readings.

PMID- 15945469
TI  - Setting up a beta-blocker protocol to prevent cardiac complications.

PMID- 15945470
TI  - CMS proposes changes in H&P rule.

PMID- 15945471
TI  - Robot: useful tool or costly coat rack?

PMID- 15945472
TI  - Robot coming? How you can prepare.

PMID- 15945473
TI  - Tips for planning new surgical facilities.

PMID- 15945474
TI  - When coaching and counseling fail.

PMID- 15945475
TI  - Scheduling a delay between 2 surgeons.

PMID- 15945476
TI  - An ASC fine-tunes its charge capture.

PMID- 15945477
TI  - Fastest facilities use more staff for cataracts.

PMID- 15945478
TI  - [Brugada syndrome].
AB  - Brugada syndrome is believed to be responsible for 4 to 12% of all sudden deaths
      and for 20% of deaths in patients with structurally normal hearts. As a distinct
      clinical entity with a high risk of sudden cardiac death it was first described
      in 1992. The syndrome characterized by ST segment elevation in right precoardial
      leads V1 to V3 unrelated to ischemia and by electrolyte disturbance without
      obvious structural heart disease. The clinical findings are based on ECG and
      syncope or sudden death. The arrhythmia leading to sudden death is a rapid
      polymorphic ventricular tachycardia. The electrocardiographic signature of the
      syndrome is dynamic and often concealed, but can be unmasked by potent sodium
      channel blockers such as flecainde, ajmaline. The Brugada syndrome is a familial
      disease displaying an autosomal dominant mode of transmission with incomplete
      penetration and with incidence ranging between 5 and 66 per 10,000. The syndrome
      has been linked to mutations in SCNA5, the gene encoding for the a subunit of the
      sodium channel. Implantation of an automatic cardiverter-defibrillator is the
      only currently proven effective therapy.

PMID- 15945479
TI  - [Cardiac arrhythmias. Diagnostic and therapeutic decision-taking].
AB  - Last 40 years of growing knowledge of the mechanisms of cardiac arrhythmias has
      unambiguously demonstrated therapeutic superiority of non-pharmacological
      treatment over antiarrhythmic drugs, which are in these days rather used in acute
      phase or moderate forms of tachyarrhythmias. Diagnosis of bradyarrhythmias relies
      mainly on bradycardia symptoms, bradycardia detection on the surface ECG and
      their mutual time correlation. Electrophysiological study stands aloof in these
      cases. Permanent cardiac stimulation dominates unequivocally in the therapy of
      bradyarrhythmias. Electrophysiological study has taken a unique place in the
      tachycardia therapy, since it allows inducing reproducibly tachyarrhythmia and by
      means of its mapping to determine its course. Thus, a completely new,
      "intracardiac" view on the arrhythmia mechanism has evolved and considerably
      weakened the diagnostic importance of the surface ECG. Radiofrequency catheter
      ablations represent a rapidly evolving causal therapeutic modality of
      tachyarrhythmias, especially in the absence of structural heart disease.
      Significantly decreased left ventricular ejection fraction combined with
      tachycardia symptoms should raise suspicion of life threatening ventricular
      arrhythmias, which are nowadays successfully treated by implantation of a
      cardioverter-defibrillator.

PMID- 15945480
TI  - [Indications for electrophysiologic examination in clinical praxis].
AB  - During the past 35 years, cardiac electrophysiologic examinations have evolved
      into widely employed standard clinical tools in the diagnostics of different
      symptoms--like unexplained syncope or palpitations etc., as well as in the
      management of different cardiac arrhythmias. This review article presents current
      opinion regarding the indications and interpretations of invasive
      electrophysiologic examination in the bradyarrhythmias and in supraventricular
      and ventricular tachyarrhythmias. It is stressed that in the course of these
      studies, therapeutic catheter ablation procedures are being performed nowadays in
      many cases. Finally, the role of programmed ventricular stimulation in the risk
      stratification of patients with ischemic and nonischemic cardiomyopathy is
      discussed. It is emphasized that nonpharmacologic treatment of clinically
      significant brady- and tachyarrhythmias is the dominant therapeutic option at
      present. The dynamical progress in this field of cardiology may require periodic
      updating of the indications for electrophysiologic examination as well as the
      evaluation of their contribution to the treatment of arrhythmias and to the
      assessment of serious arrhythmias risk on which prophylactic therapy may be
      based.

PMID- 15945481
TI  - [Ischemic mitral regurgitation. Clinical review emphasizing the surgical
      treatment].
AB  - Ischemic mitral regurgitation represents comparatively frequent complication of
      the myocardial infarction. Presence of the ischemic mitral regurgitation has a
      negative effect on the immediate mortality after the myocardial infarction and on
      the long-term survival. Ischemic mitral regurgitation is a functional, not
      structural impairment of the mitral valve and it is caused by altered geometry of
      the left ventricle. The article deals with the development and pathophysiology
      namely of the chronic ischemic mitral regurgitation and with the contemporary
      potential of surgical treatment of that serious complication of the ischemic
      heart disease.

PMID- 15945483
TI  - [Genomic imprinting and human pathology].
AB  - Genomic imprinting is an epigenetic form of regulation of gene expression.
      Imprinted genes are transcribed from one allele of specific parental origin. Such
      genes are normally involved in embryonic growth and behavioral development.
      Deregulation of imprinted genes has been observed in a number of human diseases
      as gestation trophoblastic disease, Prader-Willi, Angelmann and Beckwith
      Wiedemann syndromes and plays significant role in the carcinogenesis. Review of
      recent knowledge on mechanism and regulation of imprinting is presented in this
      paper.

PMID- 15945482
TI  - [Benefits and risk of the modern combined hormonal contraception].
AB  - The combined hormonal contraception is the most efficient reversible variety of
      family planning. The modern low doses combined hormonal contraception have a high
      efficacy with minimal risks. Users are still in risks of cardiovascular
      complications. The combined hormone contraception also has positive
      noncontraceptive effects on menstrual disorders, hyperandrogenism, cysts of
      ovary, pelipathy etc. The benefits are higher than the risks only when respecting
      the basic rules of the combined hormonal contraception prescription.

PMID- 15945484
TI  - [Depressive disorder in cardiovascular, neurological and oncologic diseases].
AB  - The discovery of antidepressants meant undoubtedly a revolution in psychiatry.
      The development of antidepressants has changed the image of psychiatry, brought a
      progress in the treatment and became a stimulus for investigations of mental
      illnesses ethiopathogenesis. Nowadays it is becoming evident, that many biologic,
      psychologic and with high probability also social aspects are common for the
      depression and for somatic disorders. The more prominent is the association of
      depression with cardiovascular disease. Neurological disease, mainly the
      epilepsy, Parkinson disease an stroke represent further common sphere.
      Historically, association between cancer and depression was identified first. The
      article presents epidemiological data and analyses possible common mechanisms of
      somatic disease and depression. In the last part the actual data about the
      treatment of depression in individual somatic diseases are described.

PMID- 15945485
TI  - [Lower urinary tract infections in urogynaecology].
AB  - Urinary tract infections belong among the most common infectious diseases in
      adult women. Sporadic infection is usually not a diagnostic and therapeutic
      problem. Recurrent lower urinary tract infections significantly decrease the
      quality of life of the affected women. Colonisation of the vagina, vulva and the
      perineum by the uropathogens is the main risk factor of any urinary infection,
      but only concomitant action of some other factor (e.g. immunosuppression,
      urethral stenosis, urolithiasis, urethral diverticulum, diabetes and urinary
      incontinence) can induce the recurrent infection. Correct primary treatment and
      proper used preventive method is highly advantageous not only from the individual
      but also from the global point of view (high diagnostic and therapeutic expenses,
      increase of resistance and imminent success decrease of the modern treatment).
      Continuous low dose antimicrobial treatment is the most common prophylactic
      modality. Postcoital antimicrobial prophylaxis and immunomodulative therapy are
      the other used modalities. Local vaginal estrogen therapy is recommended in
      postmenopausal women. Estrogens improve the symptoms of the urogenital atrophy
      and decrease the vaginal pH, which is very important in prevention of the
      pathological bacterial colonisation of the vagina. Decision about the individual
      therapy and prophylaxis must be preceded by the evaluation of the risk factors
      with positives and negatives of the used drug.

PMID- 15945486
TI  - [Is tamoxifene porphyrinogenic?].
AB  - BACKGROUND: As reported in previous studies, porphyria cutanea tarda (PCT)
      developed in several tamoxifene-treated patients with breast cancer. We studied
      the group of patients with cancer having only tamoxifene therapy after the
      initial surgery. We evaluated their clinical and laboratory results and compared
      them with the results of the group of patients suffering also from breast tumor,
      but treated after the surgery with other systemic therapies, mostly with
      chemotherapy. METHODS AND RESULTS: 20 patients were complexly studied, 10 of them
      with only tamoxifene therapy, and 10 without it. Diagnosis of the breast tumor
      was histologically confirmed in all of them. With the use of laboratory methods
      we examined their urinary excretion of diagnostically important porphyrins (uro-
      and coproporphyrin), then total blood count, liver function tests (ALT and AST),
      blood sugar, cholesterin, serum iron and ferritin, and performed also
      urinanalysis and detection of possible anti-HCV antibodies. The laboratory
      examination was repeated in the patient subgroup after three months, urinary uro-
      and coproporphyrin excretion also in the the control group, for to have an
      opportunity to follow the dynamics of laboratory changes. All the patients were
      examined during their regular laboratory controls performed so as not to be
      bothered with repeated additional phlebotomies. We did not confirm in our
      patients suffering from breast tumor the results of other autors, suggesting the
      connection between tamoxifene-therapy and development of porphyria cutanea tarda.
      CONCLUSIONS: Isolated cases of PCT can be induced through the effect of various
      hepatotoxic factors. However, the influence of common porphyrinogenically acting
      noxious substances (alcohol, HCV virus or iron overload as a result of the HFE
      gene mutations) were not found in our patients.

PMID- 15945487
TI  - [Childhood diabetes in the Czech Republic: a steady increase in incidence].
AB  - BACKGROUND: The aim of the study was to assess the incidence and prevalence of
      type 1 diabetes in Czech children aged 0-15 years over the period 1989-2003.
      METHODS AND RESULTS: The cases were ascertained using two independent sources,
      the population-wide Czech Childhood Diabetes Register and the Association of
      Parents and Friends of Diabetic Children, and the completeness was calculated
      using the capture-recapture method. The background population size was obtained
      from annual reports of the Czech Statistic Bureau. Trends in incidence were
      estimated using Poisson regression. A total of 3 454 cases was ascertained, with
      an estimated deficit of 28 (95% CI 16-41) individuals. The average age
      standardized incidence was 12.0 (95% CI 11.6-12.4) / 100,000/year, and its
      average relative increase was 6.8% / year. The incidence has risen from 6.8 (95%
      CI 5.7-7.9) in 1989 to 18.3 (95% CI 16.2-20.4) in 2003. The prevalence in 2003
      was 1.01 (95% CI 0.96-0.06) cases per 1000, and its projection into the coming
      decade expects a rise to approximately 1.7/1000 in 2013. CONCLUSIONS: The present
      work shows that the Czech population has an intermediate childhood type 1
      diabetes incidence compared to other European countries, and although its
      continuous rise may be expected, the prevalence is very unlikely to reach
      dramatically high figures.

PMID- 15945488
TI  - [Infrared pupilometry measured by digital photography].
AB  - BACKGROUND: Pupil size is mainly controlled by the action of parasympathetic and
      sympathetic nerves. Measurement of pupil size and reaction to light are important
      in both experimental and clinical settings. METHODS AND RESULTS: We have
      established infrared pupilometry using a commercially available digital camera
      and a calculation with standard computer software. Volunteers were habituated in
      a dark room for five minutes before pupil evaluation. Pupil measurement was
      repeated three times and the diameter was calculated according to the following
      formula: D(mm)=30/S(pix)*D(pix), where D(pix) and D(mm) represent the pupil size
      in pixels and millimetres, respectively, and S(pix) was the length in pixels of a
      30 mm standard. Our method was validated by the measurement of the diameter of
      calibration circles printed on a white sheet of paper. Deviation from the actual
      size was less than 3%. We also compared the results of pupil size obtained by our
      method, with the results of the pupilometer Pupillscan II measurement. The
      relative difference between the two methods was always less than 5%. The
      applicability of the method was illustrated by measurement of the pharmacodynamic
      effect of the single dose of tramadol (100 mg p.o.) in seven volunteers, compared
      with control placebo-treated volunteers. CONCLUSIONS: The proposed method is
      precise and sensitive enough to be used for pupil size determination.

PMID- 15945489
TI  - [Serum concentrations of adiponectin in patients with restrictive and purgative
      subtype of mental anorexia].
AB  - BACKGROUND: The aim of our study was to compare serum concentrations of
      adiponectin, leptin and other selected parameters in female patients with
      restrictive subtype of anorexia nervosa (n=15), (RMA), binge/purge subtype of
      anorexia nervosa (n=11) (PMA) with age-matched healthy females, (C, n=14).
      METHODS AND RESULTS: RMA patients had the most severely decreased body mass index
      (BMI) and serum leptin levels of the three groups studied. These parameters were
      also significantly lower in PMA relative to C group. (BMI: RMA 14.61 +/- 0.49
      kg/m2, PMA 17.30 +/- 0.25 kg/m2, C 23.21 +/- 0.96 kg/m2; leptin: RMA 1.39 +/-
      0.31 ng/ml, PMA 3.72 +/- 0.77 ng/ml, C 9.17 +/- 1.53 ng/ml). In contrast, serum
      adiponectin levels were markedly increased in RMA patients (57.28 +/- 4.86 ug/ml)
      relative to other groups (PMA 40,25 +/- 2.18 microg/ml, K 26.84 +/- 2.40
      microg/ml). Serum leptin levels positively correlated with BMI in all groups
      studied (r = 0.56, p = 0.002), while the inverse relationship was found for
      adiponectin levels and BMI (r = -0.72, p = 0.000003). The hormonal concentrations
      were measured by commercially available RIA and ELISA kits. CONCLUSIONS: The most
      significant changes of serum adiponectin and leptin levels were found in the RMA
      group with most severely decreased BMI and body fat content relative to rest of
      the groups. Possible role of increased adiponectin levels in the etiopathogenesis
      and/or metabolic changes in patients with anorexia nervosa is under the scope of
      our current investigations.

PMID- 15945490
TI  - [Severe lead intoxication after ingestion of lead shots].
AB  - The authors describe severe lead intoxication in a male patient who swallowed
      about 20 lead shots by accident. It caused an acute lead intoxication with
      highest blood lead reaching about 2.4 fold value of biological exposure limit for
      blood lead concentration for occupational exposure (0.97 mg/l), coproporphyrines
      in urine reaching 30 fold increase of biological exposure limit (1000 nmol/mmol
      creatinine), and 5-aminolevulic acid about 2.7 fold increase of biological limit
      (35.0 micromol/mmol creatinine). After first dose of chelating antidote (calcium
      disodium edetate, EDTA) the patient excreted 9.0 mg of lead in urine during 24
      hours. Clinical symptoms and results of examinations led to suspicion of
      gastroduodenal ulcer at first. Diagnosis was defined after detailed examination
      and completing of the patient's history. Typical symptoms of intoxication
      developed--normocytic normochromic anemia and saturnine colics. Elimination of
      shots from digestive tract and treatment with 8 doses of antidote led to crucial
      change and improvement in the course of one month. The article should serve as an
      instruction to early recognition of lead intoxication.

PMID- 15945491
TI  - Dermatology nursing: spreading good practice in primary care.

PMID- 15945492
TI  - Community nursery nurses come of age.

PMID- 15945493
TI  - Healthier lifestyles series: 2. Smiling through the ages--how to keep your teeth
      for life.
AB  - The key aspects of dental health in babies and children, teenagers, adults and
      the elderly are outlined, including tips for prevention of dental disease.

PMID- 15945494
TI  - Breast-feeding: encourage mothers to "give it a go"!
AB  - Breast-feeding is a part of the Government health agenda with a particular
      emphasis on encouraging those mothers who are least likely to breast-feed.
      Current and recent breast-feeding support materials from the Department of Health
      outline good practice for Primary Care Trusts, in line with targets for the
      increase in breast-feeding initiation. Breast-feeding reduces health
      inequalities, in the short and long term. The 2005 National Breastfeeding
      Awareness Week has the key message "Give it a go!" and materials including a
      Local Action booklet are available.

PMID- 15945495
TI  - Atopic eczema: nurse-led care--2. Treatments.
AB  - In the second of a two-part article on eczema, a nurse consultant in dermatology
      discusses treatments. The principles of selecting and using emollients and the
      use of topical corticosteroids are also discussed. The importance of educating
      the patient on how to use emollients, topical corticosteroids and other
      treatments is emphasised, particularly in the context of nurse-led eczema
      clinics.

PMID- 15945496
TI  - Nutrition for toddlers: the foundation for good health--1. toddlers' nutritional
      needs: what are they and are they being met?
AB  - Changing lifestyles and dietary patterns over the last 20 years have conspired to
      increase a number of imbalances in the dietary patterns of the toddler population
      in the UK. The risk of the development of nutritionally-related diseases such as
      obesity and iron deficiency anaemia are a cause for concern. In this review, the
      paradox of falling levels of energy intake against a backdrop of rising levels of
      obesity is explored. New areas of research are highlighted, the findings of which
      have the potential to enhance the health and well-being of toddlers. Part 1 of
      the review considers current nutritional recommendations for toddlers and whether
      they are being met. Part 2, to be published in issue 15(3) of Journal of Family
      Health Care, will consider issues of particular concern, including the influence
      of contemporary lifestyles; dietary imbalances; obesity; and iron deficiency
      anaemia. Practical steps will be suggested to prevent obesity and iron deficiency
      anaemia.

PMID- 15945497
TI  - Physiological endocrine control of energy homeostasis and postprandial blood
      glucose levels.
AB  - The aim of this review is to analyze the different components and the feedback
      mechanisms involved in the normal control of energy homeostasis and postprandial
      blood glucose levels. Such control involves exogenous and endogenous factors:
      while the former include quantity and quality of food intake, the latter involve
      the balance of glucose intestinal absorption (postprandial period), glucose
      production and release by the liver and its consumption by peripheral tissues.
      Adequate secretion and peripheral metabolic effects of insulin play a key role in
      the control of both processes. Insulin secretion is controlled by the level of
      circulating substrates and by gastrointestinal hormones. The mechanism for the
      immediate control of blood glucose levels is modulated by energy homeostasis,
      with the participation of the above mentioned hormones and others produced at the
      classical endocrine system and adipose tissue, whose actions integrate at the
      central nervous system. The alteration of such delicate mechanism of control
      causes diseases such as diabetes; therefore, identification of the multiple
      components of this mechanism and comprehension of its normal function would
      facilitate the selection of effective strategies for diabetes prevention and
      treatment.

PMID- 15945498
TI  - Stem cell-based treatments for gynecological solid tumors.
AB  - BACKGROUND AND OBJECTIVE: We have recently assisted to an increasing scientific
      interest and a new research effort in the field of stem cell-based therapy. Since
      the late 1980s hematopoietic stem cells (HSC) have been used to set up
      therapeutic strategies for the treatment of solid tumors such as gynecological
      cancers. In this context, different approaches have been suggested and clinically
      investigated. STATE OF THE ART: In the autologous setting we can describe the
      well-known use of HSC as hematologic support to high-dose chemotherapy regimens,
      and the use of HSC as a source of dendritic cells for cancer vaccination
      protocols. In our institution a long-term experience has been developed in high
      dose chemotherapy with autologous HSC transplantation as first-line treatment of
      advanced ovarian cancer, and in the use of cytokines both for HSC collection and
      for post-transplantation hematopoietic recovery and immune reconstitution. An
      alternative approach consists of allogenic HSC transplantation following either
      myeloablative/standard or non-myeloablative/reduced conditioning regimens, which
      have been proposed as new adoptive immunotherapeutic treatments for different non
      hematologic malignancies. PERSPECTIVES: Future strategies in the use of HSC in
      oncology comprise the possibility of HSC ex-vivo expansion, the use of umbilical
      cord blood HSC, and the development of HSC-based gene-therapy programs. Further
      investigations are expected in the new field of cancer stem cells.

PMID- 15945500
TI  - A study on the polymicrobial etiology of root canal infections in anterior non
      vital teeth in a government hospital in Kolkata, India.
AB  - A total of 52 patients having non-vital anterior teeth who attended at the
      Department of Conservative Dentistry of a Government Dental College of the city
      of Kolkata, India where studied for isolation of different microflora in the root
      canals of the non-vital teeth. 41 (78.8%) out of 52 cases studied showed the
      presence of microorganisms in the root canal of the teeth. A total of 83
      different strains were isolated. The anaerobic organisms constituted 30.1% of the
      total isolates. 51.7% of the root canals showed presence of polymicrobial
      etiology of the non-vital teeth.

PMID- 15945499
TI  - Significant decrease of IgE antibodies after a three-year controlled study of
      specific immunotherapy to pollen allergens in children with allergic asthma.
AB  - BACKGROUND: Specific immunotherapy (SIT) in children being not an optional
      treatment should be administered as soon as possible, also in children aged 2-3
      years, due to the very early asthma and rhinitis onset, contrarily to opponents
      continuing to stress the danger of anaphylactic reactions without displaying
      reliable data. MATERIALS AND METHODS: We report 56 children who underwent SIT and
      56 controls seen consecutevely at the Allergy and Immunology Division, Department
      of Pediatrics, University of Rome "La Sapienza". The control group was treated
      with all appropriate medications. RESULTS: They were highly in favor of SIT with
      statistically significant differences. We stress that IgE antibodies
      significantly decreased after treatment only in the study group, and IgG
      antibodies very significantly increased after treatment only in the study group.
      DISCUSSION: We demonstrate that SIT is the only treatment which can alter the
      natural course of respiratory diseases, whereas drugs represent only a
      symptomatic treatment.

PMID- 15945501
TI  - The influence of ipratropium bromide in the recovery phase of methacholine
      induced-bronchospasm.
AB  - BACKGROUND: The protective effect of Ipratropium Bromide (IB) in the methacholine
      induced bronchospasm is well known from some time. The objective of the present
      study was to assess whether a pretreatment with IB may influence the subsequent
      phase of methacholine-induced bronchospasm relief. METHODS: Sixteen patients with
      bronchial hyper-reactivity (PD20 FEV1 < 200 microg) were randomly assigned to
      three methacholine challenge tests at a 48 to 72 hours interval apart. In the
      first test IB was inhaled before the challenge (pre-IB), in the second IB was
      administered soon after the PD20 FEV1 (post-IB), and in the third no treatment
      was given (control). RESULTS: The pre-IB PD20 FEV1 (695 +/- 587.6 microg) was
      significantly greater (p < 0.0001) than that of post-IB (82.2 +/- 49.18 microg)
      and of control (73.9 +/- 41.8 microg). The dose response slope (DRS) (decline
      percentage of FEV1/cumulative methacholine dose), in pre-IB was greatly lower (p
      < 0.0001) than that in post-IB and in control. During the bronchospasm relief
      phase, the increase of FEV1 measured after 5, 10, 15, 30 and 60 minutes from the
      PD20 FEV1 was significantly greater in post-IB (p < 0.05) compared with the other
      two conditions. Conversely, the recovery slope (RS) (increase percentage of FEV1
      at 60 minutes after PD20 FEV1 x cumulative methacholine dose) was significantly
      more efficient (p < 0.001) in pre-IB than in post-IB and in control. CONCLUSION:
      In conclusion, ipratropium bromide confirmed to have a good protective activity
      against methacholine-induced bronchospasm; the pre-administration of ipratropium
      bromide showed also a positive effect on the recovery phase.

PMID- 15945502
TI  - Bronchial hyperresponsiveness in asthmatic adults--a long-term correlation study.
AB  - BACKGROUND: Bronchial hyper responsiveness (BHR), is a risk factor for asthma. It
      is a state in which excessive narrowing of the airways occurs in response to
      varying stimuli. BHR seems to be due to the interaction of multiple factors and
      its relation to asthma is complex. Asthma without BHR is unusual. Indeed,
      patients who show a higher degree of symptoms have higher levels of BHR. To date
      no study has investigated the correlation between BHR in mild persistent
      asthmatic adults and a long-term therapy of five years. The aim of this study is
      to evaluate (i) the role of BHR in the clinical evaluation of asthma, (ii) the
      correlation between BHR and therapy in asthma. METHODS: Seventy patients (were
      recruited 34 men, age 21-55 years) suffering from: (a) mild seasonal allergic
      asthma (17/70), (b) mild perennial allergic asthma (34/70) and (c) mild non
      allergic [corrected] asthma (19/70). 14 patients from group (a) and 28 patients
      from group (b) were treated with inhaled beta2-agonists, beclomethasone,
      disodiumcromoglycate and immunotherapy. 14 patients from group (c) underwent the
      same treatment regimen without immunotherapy. All patients were evaluated with a
      metacholine challenge test. The BHR (PD20 FEV1) was calculated at baseline and
      after a two-year symptom free period. Fifteen pts were followed-up for five years
      with an evaluation every year. All other patients did not receive any treatment.
      The results (expressed as mean +/- SE) were evaluated. RESULTS: Fourteen pts and
      three pts from group (a) showed a mean BHR value of 984 +/- 3.66 and 674 +/-
      2.06; 343 +/- 7.60 and 208 +/- 7.70 respectively. The results were not
      statistically significant Twenty-eight and six pts from group (b) showed mean
      values of 685 +/- 1.45 and 1405 +/- 5.65; 856 +/- 7.09 and 435 +/- 2.20 with
      apparent improvement for the former. Five pts and fourteen pts from group (c)
      showed mean value of 2682 +/- 7.85 and 2099 +/- 6.82; 816 +/- 2.53 and 877 +/-
      4.78 respectively. As for the 5-yr follow up ten pts and five pts from group (b)
      showed mean values of 705 +/- 1.6 and 861 +/- 7.15; 911 +/- 7.3 and 457 +/- 2.3
      respectively. CONCLUSIONS: Although the clinical picture improved with therapy,
      BHR was not significantly affected in any patient group, at two and five years of
      follow-up. Furthermore, no correlation was found between the clinical picture and
      PD20 FEV1 values. BHR seems to result from the interaction of multiple factors
      that are worth further investigating. BHR cannot be considered a marker of
      disease activity in asthma and therefore is not a useful tool for guiding asthma
      therapy.

PMID- 15945503
TI  - Management of acute pancreatitis in emergency.
AB  - This review focuses on the medical and endoscopic approachs to patients with
      acute mild or severe pancreatitis. Acute pancreatitis is an acute inflammatory
      process of the pancreas whose the main determinant of the outcome is the extent
      of pancreatic necrosis. After the diagnosis, a severity assessment using scoring
      systems and early contrast enhanced Computed Tomography should be performed in
      all patients within 48 hours from the admission. All cases of severe acute
      pancreatitis should be managed initially in intensive care units with full
      systems support. Patients with gallstone pancreatitis should have definitive
      Endoscopic Retrograde Colangio-Pancreatography (ERCP) or surgical management of
      the gallstones.

PMID- 15945504
TI  - Circulating angiogenic cytokines in patients with advanced non-small cell lung
      cancer: correlation with treatment response and survival.
AB  - Tumor angiogenesis is stimulated by a pro-angiogenic shift in both inducers and
      inhibitors of endothelial growth. To study this shift, we measured serum and
      plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast
      growth factor (bFGF), endostatin, and thrombospondin 1 (TSP1) in 21 advanced non
      small cell lung cancer (NSCLC) patients and 46 healthy control subjects. In
      addition, we assessed the relevance of these levels to disease outcome. Cytokine
      levels were prospectively measured in plasma and serum by enzyme-linked
      immunosorbent assay at three times: before chemotherapy and at 1 and 12 weeks
      following initiation of chemotherapy. In NSCLC patients, serum VEGF levels
      (sVEGF) were elevated (p<0.001), whereas serum and plasma TSP1 levels were lower
      (p=0.012 and p=0.004, respectively) than in healthy control subjects.
      Pretreatment plasma endostatin and serum bFGF levels were higher in NSCLC
      patients than in healthy controls (p=0.05 and 0.01, respectively). Change in
      sVEGF at week 12 after initiation of chemotherapy correlated with response to
      therapy (p=0.002). Patients with pretreatment sVEGF levels <500 pg/mL had a
      median survival of 11 months, but those with sVEGF >500 pg/mL had only a 6
      months' median survival (p < 0.03). In NSCLC patients, VEGF levels are increased,
      whereas TSP1 levels are decreased, which may trigger and sustain tumor
      angiogenesis. High levels of serum VEGF at the time of presentation with NSCLC
      may predict worse survival.

PMID- 15945505
TI  - Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late
      effects surveillance system.
AB  - The aim of this study was to analyze cisplatin-induced ototoxicity in a recent
      study trial. Seventy-four patients who had received cisplatin for the treatment
      of osteosarcoma (median cumulative dose: 360 mg/m2) were investigated
      prospectively for ototoxicity in a multicenter trial. Hearing function was tested
      by audiometry. We evaluated the incidence and dependencies of hearing loss. After
      cessation of therapy, 51% of the patients showed a hearing loss of >20 dB in the
      frequency range of 4-8 kHz. Only in one patient a hearing loss was found at 2
      kHz, and in none at 1 kHz. At a cumulative cisplatin dose of < or = 240 mg/m2,
      almost no ototoxicity was found. Incidence and magnitude of hearing loss
      increased significantly with a higher cumulative dose. Furthermore, hearing
      thresholds were significantly poorer in children <12 years. A further follow-up
      investigation showed only a marginal change in hearing function. We conclude that
      ototoxicity is moderate in our group of patients and probably irreversible.

PMID- 15945506
TI  - Cytokine genotype polymorphisms in breast carcinoma: associations of TGF-beta1
      with relapse.
AB  - Markers of angiogenesis, cell proliferation, and cytokine regulation are
      associated with the development and course of autoimmune and malignant diseases.
      We investigated associations between cytokine production genotypes in breast
      cancer patients compared with controls and explored associations with known
      prognostic indices and relapse status. Eighty-eight females with breast carcinoma
      (BC) were studied in this case-control study comparing the cytokine genotypes of
      TNF-alpha TGF-beta1, IL-10, IL-6, and IFN-gamma with controls. Cytokine
      polymorphisms were identified by sequence-specific primers for codons, introns,
      or promoters regulating cytokine production. Patient characteristics, such as
      estrogen and progesterone receptor status, DNA ploidy, Her-2 neu expression,
      lymph node involvement, tumor size, and relapse status were evaluated. Cytokine
      genotypes were not associated with breast cancer compared with controls.
      Correlations between TGF-beta1 high-production genotypes and greater than four
      positive lymph nodes (OR=2.3; p=ns) and TNF-alpha high-production genotype and
      the mean level of estrogen receptor expression (66 +/- 24 vs. 34 +/- 36, p=0.016)
      were identified. The median patient follow-up interval from diagnosis to
      evaluation was 50.1 months (range 13-387 months). Relapse status was known for 84
      of the patients. The odds of relapse in TGF-beta1 codon 10 CC genotypes was 2.81
      times that in TGF-beta1 high-production genotypes (OR=2.81; 95% CI for OR: 1.0,
      7.8; p=0.04). Mean progesterone receptor expression was decreased in relapsed
      patients (40.9 +/- 29.9% vs. 23.1 +/- 24.5, p=0.05). The other cytokine genotypes
      studied (IL-10, IL-6, IFN-gamma, and TNF-alpha production were not associated
      with breast cancer overall or relapse status. In this study, TGF-beta1 low
      production genotypes (TGF-beta1 10 CC) were associated with an increased odds of
      disease relapse. This finding should be confirmed in a longitudinal study to
      further investigate the regulatory function of cytokine production as a
      prognostic indicator of relapse.

PMID- 15945507
TI  - A phase II study on the safety and efficacy of 5-fluorouracil, epirubicin,
      cyclophosphamide (FEC) followed by paclitaxel in the adjuvant treatment of breast
      cancer.
AB  - The incorporation of a taxane into an anthracycline-containing regimen in the
      adjuvant treatment of breast cancer is a promising approach. In this study, we
      aimed to evaluate the safety and efficacy of four cycles of FEC (fluorouracil 500
      mg/m2, epirubicin 70 mg/m2, cyclophosphamide 500 mg/m2, every 3 weeks) followed
      by four cycles of paclitaxel (175 mg/m2 every 3 weeks) in the adjuvant treatment
      of node-positive and other high-risk breast cancer patients. A total of 88 female
      patients were enrolled. Mean age (+/- SD) of the patients was 47 +/- 10 (min: 24;
      max: 71). The patients were followed for a median of 48 months (min: 20; max:
      64). The most common side effects were nausea-vomiting (grade I-II: 91%; grade
      III: 2%), as well as hematological toxicity (grade I-II: 70%; grade III: 3%).
      Although all patients experienced some degree of toxicity, it was severe enough
      to be classified as grade III or IV in only 10 (11%) of the cases. Of note, six
      (8%) patients had grade I and only one (1%) had grade II cardiotoxicity. No grade
      III or IV cardiotoxicity was observed. The full eight cycles of study treatment
      could be administered to 75 patients (85%). Side effects necessitated the
      reduction of the doses of FEC and paclitaxel in one (1%) and three patients (3%),
      respectively. Median overall (OS) and disease-free survival (DFS) have not yet
      been reached. Five-year OS and DFS have been estimated to be 78% and 61%,
      respectively. We conclude that FEC followed by paclitaxel is a well-tolerated and
      feasible regimen in the adjuvant treatment of early breast cancer. Its efficacity
      is comparable with other commonly used regimens and merits evaluation in a phase
      III study.

PMID- 15945508
TI  - Regulation of Msx2 gene expression by steroid hormones in human nonmalignant and
      malignant breast cancer explants cultured in vitro.
AB  - Muscle segment homeobox genes, which regulate developmental programs and are
      expressed in embryonic and adult tissue, play a role in development of some
      malignancies. There are no reports on the expression of these families of genes
      in breast cancer tissue. The aim of this study was to compare expression of Msx2
      gene in breast cancer of different genotypes as well as in surrounding
      nonmalignant tissues. Explants obtained during surgery were divided according to
      their sex steroid receptor status determined by immunocytochemistry. Four
      explants obtained from malignant and nonmalignant tissue of each individual
      patient were incubated in a control medium or with the addition of progesterone
      (10(-7) M) alone, estradiol 17 beta (10(-5) M) or both. The relative level of
      Msx2 transcripts was evaluated by a semiquantitative RT-PCR and cell
      proliferation by Alamar Blue test. Results of RT-PCR analysis showed that the
      relative expression of Msx2 gene depended on the presence of ER/PR receptors both
      in nonmalignant and malignant tissues Relative amount of Msx2 mRNA was the
      highest in surrounding nonmalignant ER+/PR- and ER-/PR+ tissue, whereas in ER-/PR
      and ER+/PR+ tissue it was 1.4-1.6-fold lower. Tumorigenesis led to about a
      twofold decrease in the relative amount of Msx2 mRNA except for ER+/PR+
      immunophenotype, where no changes were observed. Addition of estradiol or
      progesterone to the culture of ER-/PR- type tissue explants did not change
      significantly the relative amount of Msx2 gene mRNA. An opposite effect was
      observed in ER+/PR- type of tissue. Addition of estradiol alone, or estradiol and
      progesterone together to tissue culture explants decreased two to three fold the
      relative amount of Msx2 gene mRNA in both, malignant and surrounding tissues.
      Progesterone alone had no effect on Msx2 gene expression in this type of tissue.
      The most complicated regulation was observed in ER+/PR+ type of tissue. Culture
      of tissue explants supplemented with estradiol significantly increased the
      relative amount of Msx2 gene mRNA in the surrounding tissue. Progesterone
      enhanced the stimulatory effect of estradiol in surrounding tissues but not in
      the malignant tissue. Increased expression of Msx2 correlated with an increased
      proliferation in ER-/PR- and ER+/PR+ types, but not in ER+/PR- type of tissues.
      In conclusion, obtained results provide evidence that estrogen affects Msx2 gene
      expression. Significant changes in the relative amount of Msx2 gene mRNA and lack
      of canonical ERE element in 5'-upstream sequence of this gene suggest that
      regulation takes place indirectly probably by protein-protein interaction. The
      decrease in the relative amount of Msx2 gene mRNA in ER+/PR- type tumor suggests
      that progesterone also affects Msx2 gene expression by an indirect mechanism(s).

PMID- 15945509
TI  - Management of cancer-related fatigue.
AB  - Fatigue is among the most commonly reported symptoms of patients with cancer,
      with prevalence exceeding 60% in many studies. It is among the most distressing
      symptoms associated with cancer and cancer treatments because it substantially
      disturbs patients' quality of life and ability to function optimally on a daily
      basis. Although the development of this condition has been associated with a
      number of factors, its etiology remains poorly understood. Important elements to
      include in any definition of cancer-related fatigue include its pervasiveness,
      persistence, detrimental effect on quality of life, and its inability to be
      relieved by rest or sleep. Several validated questionnaires can be used to
      measure fatigue in patients with cancer, and research efforts are currently
      focused on ways to distinguish it from depression with which it shares many
      symptoms. All patients with cancer should be evaluated for fatigue, and treatment
      options should be considered for those who are experiencing excessive levels of
      fatigue. Treatment should be individualized according to the underlying pathology
      when a specific cause has been identified (e.g., anemia, sleep disorder,
      depression, or metabolic disorder). Nonspecific therapies may be useful in short-
      and long-term cancer-related fatigue management in many patients. In addition to
      older therapies, such as hematopoietics, antidepressants, corticosteroids, and
      psychostimulants, the effectiveness of the new wake-promoting agent modafinil is
      currently being studied. A more thorough evaluation of the various therapeutic
      options is required to better define their efficacy and safety profiles in this
      patient population.

PMID- 15945510
TI  - Lifestyle factors, exposures, genetic susceptibility, and renal cell cancer risk:
      a review.
AB  - Malignant kidney tumors account for approximately 2% of all new primary cancer
      cases diagnosed in the United States, with an estimated 30,000 cases occurring
      annually. Although a variety of agents, chemical and biological, have been
      implicated as causal agents in the development of renal cell carcinoma (RCC), the
      etiology remains enigmatic. The strongest association has been developed between
      cigarette smoking and renal cancer however consistent, positive associations
      between RCC and obesity, diabetes, and hypertension have also been reported. In
      addition, more recent investigations of familial kidney cancer syndromes indicate
      that a strong genetic component contributes to RCC development. Several genes
      have been identified through investigation of familial kidney cancer syndromes.
      This review article describes recent trends in RCC incidence and the currently
      identifiable etiological causes that account for approximately half of the RCC
      cases diagnoses. The remainder of this review then focuses on additional risk
      factors that have thus far not been well examined but may be helpful in
      explaining the increasing incidence trends and the geographic or racial variation
      observed nationally and worldwide.

PMID- 15945511
TI  - Cadmium and prostate cancer: a critical epidemiologic analysis.
AB  - Laboratory data implicate cadmium as a prostate carcinogen. However,
      epidemiological studies concerning the association between cadmium and prostate
      cancer are inconclusive. This article reviews the epidemiological literature on
      cadmium and prostate cancer with a special focus on highly exposed occupational
      cohorts. We searched the MEDLINE database from 1966 to 2002 for articles on
      cadmium and prostate cancer. All published analytical and descriptive studies
      that included relevant data were reviewed. In addition, we reviewed the
      experience of cohorts highly exposed to cadmium in nickel-cadmium battery plants.
      Of 4 descriptive studies, 3 reported a positive association between cadmium and
      prostate cancer. Of 10 case-control studies, 5 (50%) reported a positive
      association. Of 11 cohorts studies, 3 (33%) found a positive association.
      Finally, 4 studies on cohorts exposed in occupational nickel-cadmium batteries
      were identified and analyzed. The summary score of the standardized mortality
      ratios (SMRs) was weakly but not significantly positive 126 (95% confidence
      interval C.I.: 83-184). In contrast to laboratory studies, epidemiological
      studies do not convincingly implicate cadmium as a cause of prostate cancer.
      Future epidemiological studies that attempt to resolve the discrepancy between
      laboratory and epidemiological studies of cadmium carcinogenesis may benefit from
      incorporating biological measures of cadmium exposure.

PMID- 15945512
TI  - State-of-the art therapy for gastrointestinal stromal tumors.
AB  - Until recently, there were few effective therapeutic options for patients with
      gastrointestinal stromal tumors (GISTs). Most patients undergoing even
      potentially curative resection for early-stage disease recurred if followed for a
      sufficiently long period, and treatment of advanced tumors with systemic
      chemotherapy was ineffective. Imatinib mesylate, a molecularly targeted agent
      that inhibits the KIT receptor tyrosine kinase, has now been demonstrated to be
      highly effective at inducing objective responses in GIST patients, and it
      improves overall survival. In locoregional disease, ongoing studies are assessing
      the use of imatinib pre-or postsurgery. In addition, other agents possessing
      activity against a variety of molecular targets are being tested in advanced
      disease. Questions remain about the optimal dose of imatinib, whether to continue
      drug in the setting of progressive disease, and how best to prevent or overcome
      resistance.

PMID- 15945513
TI  - Hospice care for the terminally ill: help or hindrance.

PMID- 15945514
TI  - Hospice care for the terminally ill: an absolute necessity.

PMID- 15945515
TI  - Using modeling and vicarious reinforcement to produce more positive attitudes
      toward mental health treatment.
AB  - In this study, the authors evaluated the effectiveness of a video, developed for
      this study and using principles of cognitive learning theory, to produce positive
      attitudinal change toward mental health treatment. The participants were 35 men
      and 45 women who were randomly assigned to watch either an experimental video,
      which included 3 positive 1st-person accounts of psychotherapy or a control video
      that focused on the psychological construct of self. Pre-intervention, post
      intervention, and 2-week follow-up levels of attitude toward mental health
      treatment were measured using the Attitude Toward Seeking Professional Help Scale
      (E. H. Fischer & J. L. Turner, 1970). The experimental video group showed a
      significantly greater increase in positive attitude than did the control group.
      These results support the effectiveness of using the vicarious reinforcement
      elements of cognitive learning theory as a basis for changing attitudes toward
      mental health treatment.

PMID- 15945516
TI  - The material culture of suicidal fantasies.
AB  - In this study, the author examined the content of impulsive suicidal fantasies
      among U.S. undergraduates. Of 546 participants, 45.6% reported incidents in which
      they fantasized about killing themselves. Most fantasies (95%) included explicit
      references to suicide methods, and most of those fantasies (98%) involved human
      made tools or materials (e.g., drugs, cutlery, firearms). The methods reported in
      most suicidal fantasies seem to have been suggested by the mass media. The
      findings suggest that suicidal thoughts do not occur without explicit and
      detailed information about suicide methods involving material culture.

PMID- 15945517
TI  - The Cloze procedure as a test of plagiarism: the influence of text readability.
AB  - The authors investigated whether scores on the Cloze procedure as a test of
      plagiarism would be significantly affected by the readability of text.
      Undergraduates were asked to either paraphrase or plagiarize legal documents.
      Approximately half of the participants in the paraphrase condition received
      documents that were difficult to read, whereas the other half received versions
      that were easy to read. About 2 weeks later, participants completed Cloze tests
      that were based on their rewritten paraphrased or plagiarized versions of the
      documents. As predicted, Cloze scores from the plagiarize condition were
      significantly lower than those from the paraphrase condition. However, difficult
      to-read documents, whether they had been paraphrased or plagiarized, yielded
      significantly lower Cloze scores than their easier-to-read counterparts. In spite
      of some methodological shortcomings, the results of this study suggest caution in
      the use of the Cloze procedure as a test of plagiarism.

PMID- 15945518
TI  - The effects of trial repetition and individual characteristics on decision making
      under uncertainty.
AB  - The authors examined participants' preferences between certain and uncertain
      outcomes in a multistage gambling task and the effects of individual difference
      characteristics on those preferences. In Study 1, 144 participants made choices
      in single-stage gambles under gain and loss conditions and replicated the
      certainty effect in a previous study (D. Kahneman & A. Tversky, 1979). In Study
      2, 94 participants engaged in a multistage gambling task using the same decision
      problems as those in Study 1. They also answered a questionnaire consisting of
      the Japanese version (M. Kamahara, K. Higuchi, & N. Shimizu, 2001) of the Locus
      of Control Scale (J. B. Rotter, 1966), the Reflection-Impulsivity Scale (K.
      Takigiku & A. Sakamoto, 2001), and a Japanese version (M. Terasaki, K. Shiomi, Y.
      Kishimoto, & K. Hiraoka, 1987) of the Sensation-Seeking Scale (M. Zuckerman,
      1994). The results indicated that the certainty effect (Kahneman & Tversky)
      disappears in multistage gambling tasks and that differences in reflection
      impulsivity and in gender influence the process of decision making under gain
      conditions. These results are discussed in terms of the decision strategies and
      cognitive biases involved in the multistage gambling task.

PMID- 15945520
TI  - Accessing situation model information: memory-based processing versus here-and
      now accounts.
AB  - The focus of the present research was to compare the memory-based processing and
      here-and-now accounts of situation model updating during reading. The authors
      conducted two experiments as a follow-up on work by R. A. Zwaan and C. J. Madden
      (2004), who disputed the conclusions of E. J. O'Brien, M. L. Rizzella, J. E.
      Albrecht, and J. G. Halleran (1998). The latter researchers found support for the
      memory-based processing view by showing that readers experienced reading
      difficulty on a sentence that was consistent with an updated model of the story's
      protagonist but was inconsistent with initially stated information about the
      protagonist. In contrast, Zwaan and Madden eliminated what they argued were
      confounds in the items used by O'Brien et al. and found support for the here-and
      now view. In the present article, data from 2 experiments seem to eliminate
      weaknesses inherent in both previous authors' work. Although the present results
      are consistent with the here-and-now account, they do not completely discredit
      the memory-based processing view.

PMID- 15945519
TI  - Cultural expression and black students' attitudes toward high achievers.
AB  - The authors of the present study have extended research by D. Marryshow that
      investigated African American students' attitudes toward 4 high achievers who
      differed in their approach to high achievement. D. Marryshow (1992) assessed
      students' social attitudes and perceptions of 4 high achievers with culturally
      distinct achievement orientations. In the present research, the authors assessed
      students' academic attitudes and perceptions of the same 4 high achievers. In
      addition, the present study includes Black children's predictions of their
      parents' and peers' attitudes toward these high achieving students. The results
      generally supported the authors' hypothesis that African American children would
      report a preference for students who achieve via attitudes and behaviors
      congruent with African American cultural values. The children also predicted that
      their parents and their Black peers would prefer these same African American
      culturally oriented high achievers. The findings suggest that Black children who
      prefer African American cultural modes of achievement may find themselves at odds
      with classroom demands geared toward learning in the mainstream cultural mode and
      thus may be at increased risk of academic failure.

PMID- 15945521
TI  - Longevity, big five personality factors, and health behaviors: presidents from
      Washington to Nixon.
AB  - In this study, the positive correlation between conscientiousness and death age
      discovered by H. S. Friedman et al. (1993, 1995) was replicated for 32 American
      presidents. Conscientiousness scores, using the Big Five variables produced by S.
      J. Rubenzer, T. R. Faschingbauer, and D. S. Ones (1996, 2000), were correlated
      with death age, r(30) = .41, p < .01, and the relationship was maintained with
      controls in a multiple regression framework. Smoking, drinking, and exercise, as
      assessed by J. R. Bumgarner (1994), were also correlated in the expected fashion
      with death age. Conscientiousness was correlated negatively with smoking and
      drinking, but openness to experience was correlated negatively with smoking and
      drinking to a higher degree and also was positively correlated with exercise.
      Openness, extraversion, neuroticism, and agreeableness were not correlated with
      death age, and extraversion, neuroticism, and agreeableness were not correlated
      with smoking, drinking or exercise.

PMID- 15945522
TI  - Doyle, Holmes, and Watson--a "special" trinity.

PMID- 15945523
TI  - Venous thromboembolism: an ounce of prevention.

PMID- 15945524
TI  - A new face for an old friend.

PMID- 15945525
TI  - Long-haul air travel before major surgery: a prescription for thromboembolism?
AB  - OBJECTIVE: To investigate the Incidence of postoperative venous thromboembolism
      (VTE) in patients who had flown long distances before major surgery. PATIENTS AND
      METHODS: Using the Mayo Clinic computerized patient database, we Identified
      patients who had flown more than 5000 km before major surgery (travelers) and had
      experienced an episode of clinically significant VTE within 28 days after
      surgery. Individual medical records were reviewed for the diagnosis of VTE,
      pertinent risk factors, and outcome. We compared the Incidence of VTE in
      travelers to the incidence of VTE in patients from North America (nontravelers)
      undergoing similar surgical procedures. RESULTS: Eleven patients met our criteria
      for long-haul air travel and clinically significant VTE within 28 days after
      surgery. Compared with nontravelers undergoing similar surgical procedures, long
      haul travelers had a higher Incidence of VTE (4.9% vs 0.15%; P < .001). Compared
      with nontravelers who developed VTE, travelers were younger (P = .006), developed
      VTE earlier in the postoperative course (P = .01), had higher American Society of
      Anesthesiologists physical status classification (P = .02), and had higher
      prevalence of smoking (P = .007). Of the 11 travelers with VTE, 10 were of Middle
      Eastern origin. CONCLUSION: Prolonged air travel before major surgery
      significantly increases the risk of perioperative VTE. Such patients should
      receive more Intensive VTE prophylactic measures during the flight and throughout
      the perioperative period.

PMID- 15945526
TI  - Duration of anesthesia and venous thromboembolism after hip and knee
      arthroplasty.
AB  - OBJECTIVE: To determine whether longer duration of anesthesia predisposes
      patients undergoing orthopedic surgery to venous thromboembolism (VTE). PATIENTS
      AND METHODS: We conducted a secondary analysis of a retrospective case-control
      study that examined risk factors for postoperative VTE in postmenopausal women.
      We matched women aged 50 years and older with radiographically confirmed
      postoperative VTE (cases) by age, surgeon, year of surgery, and surgical joint
      (knee vs hip) with women without postoperative VTE (controls). Duration of
      anesthesia, operative variables, demographic data, comorbid illnesses, and
      laboratory data were determined by medical record review. RESULTS: Eighty-eight
      cases were matched with 181 controls. Duration of anesthesia of 3.5 hours or
      longer (corresponding to the upper tertile of patients) was strongly associated
      with postoperative VTE compared with a shorter duration of anesthesia (odds
      ratio, 3.58; 95% confidence Interval, 2.11-6.16; P < .001). This relationship was
      maintained after controlling for multiple covariates with propensity score
      methods, Including type of arthroplasty, route of anesthesia, type of
      antithrombotic prophylaxis, and surgical approach. In multivariate analysis, the
      Important predictors of VTE included anesthesia duration of 3.5 hours or longer,
      type of antithrombotic prophylaxis, revision (vs primary) arthroplasty, and
      allogeneic blood transfusion. CONCLUSION: We found a marked association between
      the duration of anesthesia and postoperative VTE in patients undergoing Joint
      arthroplasty. Although it is possible that unmeasured intraoperative variables
      account for this relationship, we suggest that duration of anesthesia may be an
      important risk factor for postoperative VTE after orthopedic surgery.

PMID- 15945527
TI  - Yield of genetic testing in hypertrophic cardiomyopathy.
AB  - OBJECTIVE: To determine the clinical parameters of hypertrophic cardiomyopathy
      (HCM) that correlated significantly with the presence of an identifiable
      sarcomeric mutation. PATIENTS AND METHODS: Previous comprehensive mutational
      analyses of all protein-coding exons of 8 sarcomeric genes revealed pathogenic
      mutations in 147 (38%) of 389 unrelated patients seen at the HCM outpatient
      clinic at the Mayo Clinic in Rochester, Minn, between April 1997 and December
      2001. Clinical data, extracted from patient records and blinded to patient
      genotype, were maintained in a custom database. RESULTS: In 389 unrelated
      patients, younger age at diagnosis, family history of HCM, and Increasing left
      ventricular wall thickness were all associated with Increased likelihood of
      identifying an HCM-associated sarcomeric mutation. In contrast, family history of
      sudden cardiac death, myectomy status, and anatomical subtype did not correlate
      significantly with genotype-positive status. With use of a simple scoring system
      based on age at diagnosis, left ventricular wall thickness, and family history of
      HCM, the likelihood of a sarcomeric mutation could be estimated. CONCLUSION:
      Clinical predictors of positive genotype, such as the presence of an implantable
      cardioverter-defibrillator, age at diagnosis, degree of left ventricular wall
      hypertrophy, and family history of HCM, may aid in patient selection for genetic
      testing and increase the yield of cardiac sarcomere gene screening.

PMID- 15945528
TI  - Transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is characterized by the sudden
      development of noncardlogenic pulmonary edema (acute lung Injury) after
      transfusion of blood products. Poor awareness of TRALI outside of the blood
      transfusion medicine community has led to a serious underestimation of this
      condition, currently the most Important severe complication of blood transfusion.
      Concern for the transfer of donor antileukocyte antibodies has prompted major
      changes in the management of the blood supply in some countries; however, recent
      studies have suggested alternative pathophyslological mechanisms for TRALI
      related to the shelf life of cellular blood products. Although all blood products
      have been implicated, most reported cases were associated with fresh frozen
      plasma, red blood cell, and platelet transfusions. Because many patients have
      additional predisposing factors for acute lung injury, carefully designed
      prospective studies are needed to fully assess attributable risk related to
      transfusion. The treatment of TRALI is supportive, and the prognosis is generally
      better than for other causes of acute lung Injury. As many as one third of all
      patients who develop acute lung injury have been exposed to blood products. TRALI
      may be an important and potentially preventable cause of acute lung injury.

PMID- 15945529
TI  - Outcomes after ventricular fibrillation out-of-hospital cardiac arrest: expanding
      the chain of survival.
AB  - Coronary heart disease is the most common cause of death in the United States,
      with ventricular fibrillation (VF) the most common initial rhythm when cardiac
      disease causes arrest. Survival after VF out-of-hospital cardiac arrest (OHCA)
      depends on a sequence of events called the chain of survival, which Includes
      rapid access to emergency medical services, cardiopulmonary resuscitation,
      defibrillation, and advanced care. Because of widespread implementation of
      defibrillation programs, more patients survive VF OHCAs, making subsequent care
      of these patients important. Early hospitalization must focus on potential
      neurologic injury and therapy targeted at the underlying cardiac disease and
      antiarrhythmic therapy for long-term secondary prevention of sudden death.
      Attention to certain cohorts who are at high risk despite their underlying
      disease, such as women and elderly patients, is necessary. These cohorts may have
      the greatest response to short-term and long-term therapies for cardiac
      rehabilitation. With these approaches, long-term survival and quality of life
      after VF OHCA are favorable. Broadening the focus of the chain of survival to
      include in-hospital and long-term care will further improve favorable outcomes
      achieved in an early defibrillation program.

PMID- 15945530
TI  - Complications after unintentional intra-arterial injection of drugs: risks,
      outcomes, and management strategies.
AB  - Unintentional intra-arterial injection of medication, either iatrogenic or self
      administered, is a source of considerable morbidity. Normal vascular anatomical
      proximity, aberrant vasculature, procedurally difficult situations, and medical
      personnel error all contribute to unintentional cannulation of arteries in an
      attempt to achieve intravenous access. Delivery of certain medications via
      arterial access has led to clinically important sequelae, including paresthesias,
      severe pain, motor dysfunction, compartment syndrome, gangrene, and limb loss. We
      comprehensively review the current literature, highlighting available information
      on risk factors, symptoms, pathogenesis, sequelae, and management strategies for
      unintentional intra-arterial injection. We believe that all physicians and
      ancillary personnel who administer Intravenous therapies should be aware of this
      serious problem.

PMID- 15945531
TI  - Common musculoskeletal disorders in women.
AB  - Women are prone to certain orthopedic conditions and may present to their primary
      care physician for treatment. An appreciation of the physiological and anatomical
      differences between women and men and the musculoskeletal conditions that
      commonly affect active women can aid the physician in diagnosis and treatment. We
      discuss common musculoskeletal conditions of active women including those
      affecting the low back, knee, shoulder, and foot. We also discuss common stress
      fractures seen in women. Various treatment and prevention strategies are reviewed
      and include physical therapy, bracing, medications, and surgery.

PMID- 15945532
TI  - 54-year-old man with hip pain.

PMID- 15945533
TI  - Sepsis and myocardial depression in a young woman.
AB  - Severe sepsis may be associated with depression of myocardial function,
      attributed to various inflammatory mediators. Myocardial dysfunction in sepsis is
      characterized by biventricular failure and complicates usual therapy with high
      volume fluid resuscitation and vasopressors. However, in patients who survive
      septic shock, myocardial dysfunction can improve rapidly. We describe a young
      woman with septic shock due to Streptococcus pneumoniae, complicated by severe
      but reversible biventricular dysfunction.

PMID- 15945534
TI  - Usual interstitial pneumonia complicating dyskeratosis congenita.
AB  - Dyskeratosis congenita (DC) is a rare disorder characterized by skin
      hyperpigmentation, nail dystrophy, and leukoplakia of mucous membranes. Pulmonary
      complications occur in approximately 20% of patients, although the specific
      histopathologic features, the temporal relationship between the diagnosis of DC
      and the development of pulmonary fibrosis, and the response to specific treatment
      are largely undefined. We describe 2 patients with DC who developed usual
      interstitial pneumonia. Pulmonary fibrosis developed 18 and 38 years after the
      original manifestations of DC. Both patients died of respiratory failure, 4 and 6
      months after lung biopsy. Pulmonary fibrosis in patients with DC may be linked to
      underlying abnormalities of fibroblast function.

PMID- 15945535
TI  - Pancreatic panniculitis due to pancreatic carcinoma.

PMID- 15945536
TI  - Falsely high antibiotic resistance in community-acquired E. coli UTIs requiring
      hospitalization.

PMID- 15945537
TI  - Hormone replacement therapy and coronary endothelial function in postmenopausal
      women.

PMID- 15945538
TI  - Fibromyalgia and complementary and alternative medicine.

PMID- 15945539
TI  - Regulation of nuclear transfer technology.

PMID- 15945540
TI  - Malarial hepatitis simulating fulminant hepatic failure.

PMID- 15945541
TI  - [Estimation of the efficacy of screened natural hypolipidemic compounds in a
      model of rabbit hypercholesterolemia].
AB  - Thirteen strains producing hydrophobic compounds with high hypolipidemic activity
      were screened among 657 tested strains of fungi, actinomycetes and bacteria with
      the use of 2 models. The further aim of the study was to estimate the efficacy of
      the compounds with respect to their ability to inhibit cholesterol synthesis in
      vivo. For that purpose a model of hyperlipidemia in rabbits was used. The model
      provided screening of 9 new compounds that showed satisfactory hypolipidemic
      effect evident from a significant decrease of the lipid levels in the rabbit
      serum. The study of the serum lipid profile revealed that the inhibitory effect
      of compounds No. 16 and No. 281 was similar to that of lovastatin whereas the
      serum level of general cholesterol remained decreased for a longer period.
      Compound No. 25 was of interest because of its possible use in low doses and
      significant effect on the serum triglyceride fraction.

PMID- 15945542
TI  - [Antiviral activity of oral ultralow doses of antibodies to gamma-interferon:
      experimental study of influenza infection in mice].
AB  - Course intragastric administration of ultralow doses of human gamma-interferon
      antibodies (ULD anti-IFN-gamma) to intact mice resulted in an increase of
      endogenous IFN-gamma production by the animal lymphocytes. Oral prophylactic
      administration of ULD anti-IFN-gamma significantly lowered the influenza virus
      concentration in the animal lungs at the initial stage of the aerogenous
      infection: in 2 (p = 0.05) and 3 (p = 0.07) days after the contamination. The
      therapeutic antiviral effect of ULD anti-IFN-gamma in mice with influenza was
      evident from a significant decrease of the influenza virus concentration in the
      lungs of the animals on the 4th (p = 0.05) and 5th (p = 0.07) days after the
      contamination. The antiviral effect of ULD anti-IFN-gamma after the prophylactic
      and therapeutic use is likely provided by induction of endogenous IFN-gamma.

PMID- 15945543
TI  - [Preparations for serodiagnosis of diseases due to causative agents of ixodes
      tick-borne borreliosis (Lyme disease). Communication 3. Comparative study of
      enzyme immunoassay test-systems for detection of IgM to Borrelia burgdorferi
      sensu lato].
AB  - Three foreign and one Russian ELISA test-systems for detection of IgM to Borrelia
      burgdorferi sensu lato were comparatively studied with the use of the clinical
      material in an encoded experiment. In the foreign ELISA test-systems based on the
      use of native antigens of borrelia, cross reactions with sera from patients with
      syphilis, Epstein-Barr infection, cytomegalovirus infection and systemic lupus
      erythematosus were detected. The Russian recombinant ELISA test-system
      Borreliosis-ELISA-IgM showed high sensitivity and specificity. The simultaneous
      use of the test-systems for detecting IgG and IgM significantly increased the
      efficacy of diagnosis of early borreliosis.

PMID- 15945544
TI  - [Experimental study on the effect of low molecular DNA from salmon milt in
      pseudotuberculosis infection].
AB  - The effect of low molecular DNA from salmon milt (nDNA) in experimental
      pseudotuberculosis in mice was studied. When nDNA was admiministered orally,
      dissemination of the organs by Yersinia pseudotuberculosis lowered and the
      survival of the animals infected with 100-percent lethal dose of the bacteria
      increased. nDNA decreased contamination of the epithelial cells by the microbe in
      vitro and prevented the lethal effect of the Y. pseudotuberculosis toxins on the
      mice.

PMID- 15945545
TI  - [Donor activity of methicillin resistant staphylococci in transduction
      experiments].
AB  - Antibiotic resistance gene transmission from methicillin resistant strains of
      Staphylococcus aureus (MRSA), isolated in a burn care unit, was studied in
      transduction experiments with type phages 29, 52, 52A and in experiments with
      prophage induction. The results of the experiments demonstrated high donor
      activity of MRSA. Recombinants with different antibiotic resistance phenotypes
      were revealed, but there were no methicillin resistant staphylococci among them.
      Stability of cloramphenicol resistance gene transmission in the experiments on
      specific transduction with the prophage induction could be indicative of the
      prophage localization near the chloramphenicol resistance genes. Variety of the
      antibiotic resistance combinations in the transductants from the clinical strains
      of MRSA could prove heterogeneity of the strains even under conditions of one
      hospital.

PMID- 15945546
TI  - [Comparative evaluation of activity of antibacterial agents in vitro and their
      efficacy in experimental cholera due to strains of Vibrio cholerae O1 and O139
      serogroups in albino mice].
AB  - Activity of 16 antibacterial agents against human isolates of Vibrio cholerae O1
      and O139 serogroups (P-5879, 4990, 143/23, and MO-45, P- 16065 respectively) was
      studied in vitro. The efficacy of the agents was studied in a model of
      generalized cholera in albino mice. Susceptibility of Vibrio cholerae P-5879
      (used as the control) in the in vitro experiments with respect to the
      antibacterial agents correlated with their in vivo efficacy. The strains of
      Vibrio cholerae O1 and O139 serogroups isolated within the recent years had
      transmissive markers of resistance to streptomycin,
      trimethoprime/sulfamethoxazole, tetracycline, chloramphenicol and not transmitted
      by conjugation markers of resistance to rifampicin, furazolidone, nalidixic acid.
      The specific feature of the experimental infection due to such strains was the
      failure not only of the antibacterials of the resistance spectrum of the pathogen
      but also of the antibiotics showing in vitro susceptibility (betalactams,
      fluoroquinolones) that required additional bacteriological control on the 2nd or
      3rd day of the etiotropic therapy for early replacement of the antibacterial
      agent.

PMID- 15945547
TI  - [Aortic valve stenosis: persistence of infective agents or noninfective
      inflammatory process?].
AB  - The probable risk factors leading to aortic valve calcification are not clearly
      defined. The cross-sectional study of 85 patients with vascular and valvular
      calcification was performed. Correlations between the immune tests and aortic
      stenosis severity were investigated. The predictors of aortic valve calcification
      were probably C-reactive protein and interleukin-6. The predictors of aortic
      stenosis progression were interleukin-8, antibodies of Chlamydia pneumoniae and
      cytomegalovirus, and dysregulation of complement's components. Implication of
      immune reactivity could influence aortic valve calcification.

PMID- 15945549
TI  - [Resistance of urinary tract infection pathogens and choice of antibacterial
      therapy in pediatric urologic practice].
AB  - The data on antibiotic resistance of the main uropathogens isolated from patients
      with urinary tract infection in an urologic department (319 isolates) and
      outpatient and diagnostic units (360 isolates) are presented. It was shown that
      by the antibiotic resistance the Escherichia coli isolates from the urologic
      department patients and outpatients did not practically differ: 44.1 and 47.8% of
      the isolates were resistant to ampicillin, 26.7 and 23.4% were resistant to
      amoxycillin/clavulanate, 28.9 and 24.9% were resistant to co-trimoxazole and
      26.5% was resistance to cefuroxime (outpatients). The basic differences referred
      to Pseudomonas aeruginosa: resistance to ceftazidime in 38.5% of the isolates and
      resistance to gentamicin in 36.2% of the isolates. The activity against P.
      aeruginosa could be arranged as follows in the decreasing order: amikacin =
      meropenem > imipenem > cefepime = cefoperazone/sulbactam > gentamicin =
      ceftazidime. Resistance of P. aeruginosa to fluoroquinolones (ciprofloxacin and
      levofloxacin) remained low (7.4 and 8.0% respectively). No ampicillin resistance
      was revealed in the isolates of Enterococcus faecalis.

PMID- 15945548
TI  - [Clinical basis of provocative detoxicating etiotropic therapy of chronic
      toxoplasmosis in pediatric cases].
AB  - Clinical and laboratory data on the treatment of 19 children with chronic
      toxoplasmosis were used for estimation of the efficacy of drug combination, such
      as spiramycin + lidase and lincomycin + lidase vs. the traditional therapy (co
      trimoxazole, metronidazole). The combination designed by us, i.e. spiramycin +
      lidase, lincomycin + lidase used in consecutive courses proved to be more
      efficient.

PMID- 15945550
TI  - Orchard grass or cock's foot, Dactylis glomerata.

PMID- 15945551
TI  - Got epinephrine? Many patients with anaphylaxis reportedly stuck with no
      epinephrine syringes.

PMID- 15945552
TI  - Epinephrine for anaphylaxis.

PMID- 15945553
TI  - The challenge of mild persistent asthma.
AB  - OBJECTIVE: To review the current data and treatment options for mild persistent
      asthma. DATA SOURCES: A MEDLINE search was performed for relevant articles. STUDY
      SELECTION: The expert opinion of the author was used to select studies for
      inclusion in this review. RESULTS: Current data suggest that asthma severity is
      determined early in life and that disease progression may not occur outside early
      childhood. Furthermore, no therapy has been demonstrated to clearly prevent or
      reverse structural airway changes in patients with persistent asthma. Thus, the
      primary goal of asthma therapy is to prevent disease exacerbations rather than to
      halt disease progress, at least in patients past early childhood. Published
      reports of severe exacerbations in patients with reported mild asthma may
      actually reflect inclusion of patients with more severe forms of the disease who
      were inappropriately classified in terms of asthma severity. CONCLUSION: Unlike
      the case for moderate and severe asthma, where regular therapy with inhaled
      corticosteroids is clearly the treatment of choice, clear guidelines for treating
      patients with mild persistent asthma have not been established. Patients with
      mild disease without severe exacerbations may require only the minimum therapy
      necessary for disease control.

PMID- 15945554
TI  - Anaphylaxis following ingestion of candy fruit chews.

PMID- 15945555
TI  - Lack of worldwide availability of epinephrine autoinjectors for outpatients at
      risk of anaphylaxis.
AB  - BACKGROUND: Anaphylaxis is increasing globally and often occurs in the community
      rather than in a health care setting. Epinephrine, the initial treatment of
      choice for anaphylaxis, is listed by the World Health Organization as an
      essential medication; however, the extent of its availability for outpatients is
      unknown. OBJECTIVE: To determine the availability of epinephrine for use in the
      first-aid, out-of-hospital treatment of anaphylaxis in different countries.
      METHODS: We used an investigator-designed, validated survey instrument that was
      self-administered by members of the World Allergy Organization House of Delegates
      for 2003 to 2005. Responses were tabulated by country. RESULTS: Completed surveys
      were received from all 75 representatives of all 39 countries (100% response
      rate). At the time of the survey, epinephrine autoinjectors that contained a 0.25
      or 0.3-mg dose appropriate for use in adults were available in 56.4% (95%
      confidence interval [CI], 40.8%-72%) of these countries. Widespread availability
      in Europe and availability in countries such as the United States, Canada, and
      Australia contrasted with limited availability in Asia, South America, and
      Africa. Autoinjectors that contained a 0.15-mg dose appropriate for use in some
      children were available in 43.6% (95% CI, 28%-59.2%) of the 39 countries.
      Autoinjectors that contained a dose appropriate for use in infants were not
      available in any country. Costs ranged from 30 US dollars to 110 US dollars. In
      27.3% (95% CI, 8.7%-45.9%) of the countries, no financial assistance from
      government or private insurance was available to defray the cost. CONCLUSION:
      This study raises concerns about lack of availability and affordability of
      epinephrine autoinjectors worldwide for individuals of all ages, especially for
      the pediatric population.

PMID- 15945556
TI  - Adequacy of the epinephrine autoinjector needle length in delivering epinephrine
      to the intramuscular tissues.
AB  - BACKGROUND: Epinephrine injected by an autoinjector in the anterolateral aspect
      of the thigh is the standard of care in the emergency self-treatment of
      anaphylaxis. In the United States, the autoinjector EpiPen is widely used for the
      self-treatment of anaphylaxis. OBJECTIVE: To investigate whether EpiPen
      autoinjector, with a needle length of 1.43 cm, is sufficient for intramuscular
      delivery of epinephrine in men and women. METHODS: The distance from skin to
      muscle in the anterolateral aspect of the thigh was measured in 50 men and 50
      women who had undergone computed tomography of the thighs for other medical
      reasons. For each individual, body mass index (BMI; a measure of weight in
      kilograms divided by the square of height in meters) was also calculated, and the
      individuals were classified as underweight (BMI, < 18.5), normal (BMI, 18.5
      24.9), overweight (BMI, 25.0-29.9), and obese (BMI, > or = 30.0) using standard
      definition. RESULTS: In the study participants the mean +/- SD distance from skin
      to muscle was 0.66 +/- 0.47 cm for men and 1.48 +/- 0.72 cm for women (P < .001).
      One man (obese at a BMI of 42.2) and 21 women (11 obese with a mean BMI of 35.2,
      6 overweight with a mean BMI of 30.1, and 4 normal with a mean BMI of 24.5) had a
      greater distance from skin to muscle than the EpiPen needle length of 1.43 cm.
      CONCLUSION: The distance from skin to muscle for the anterolateral aspect of the
      thigh is higher in women compared with men. This difference suggests that EpiPen
      may not deliver epinephrine to the intramuscular tissue in many women.

PMID- 15945557
TI  - Yoga intervention for adults with mild-to-moderate asthma: a pilot study.
AB  - BACKGROUND: Preliminary studies investigating yoga and breath work for treating
      asthma have been promising. Several randomized controlled trials have shown a
      benefit from yoga postures and breathing vs control, but the control in these
      cases involved no intervention other than usual care. This study advances the
      field by providing an active control. OBJECTIVE: To determine the effectiveness
      and feasibility of a yoga and breath work intervention for improving clinical
      indices and quality of life in adults with mild-to-moderate asthma. METHODS: A
      randomized, controlled, double-masked clinical trial was conducted between
      October 1, 2001, and March 31, 2003. Random assignment was made to either a 4
      week yoga intervention that included postures and breath work or a stretching
      control condition. Outcome measures were evaluated at 4, 8, 12, and 16 weeks and
      included the Mini Asthma Quality of Life Questionnaire, rescue inhaler use,
      spirometry, symptom diaries, and health care utilization. RESULTS: Sixty-two
      participants were randomized to the intervention and control groups, and 45
      completed the final follow-up measures. Intention-to-treat analysis was
      performed. Significant within-group differences in postbronchodilator forced
      expiratory volume in 1 second and morning symptom scores were apparent in both
      groups at 4 and 16 weeks; however, no significant differences between groups were
      observed on any outcome measures. CONCLUSIONS: Iyengar yoga conferred no
      appreciable benefit in mild-to-moderate asthma. Circumstances under which yoga is
      of benefit in asthma management, if any, remain to be determined.

PMID- 15945558
TI  - Asthma as a risk factor for respiratory complications after adenotonsillectomy in
      children with obstructive breathing during sleep.
AB  - BACKGROUND: Children with asthma are at increased risk for obstructive breathing
      during sleep. Adenotonsillectomy, the treatment of choice for obstructive
      breathing during sleep, is associated with significant postoperative respiratory
      morbidity. OBJECTIVE: To determine whether asthma is a risk factor for
      respiratory complications after adenotonsillectomy in children with obstructive
      breathing during sleep. METHODS: This case-control study compared 115 children
      aged 3 to 18 years with respiratory complications after adenotonsillectomy (study
      group) with 115 children without respiratory complications after
      adenotonsillectomy (control group). RESULTS: The postoperative respiratory
      complications ranged from oxygen desaturation to respiratory failure that
      required mechanical ventilation. The study group had a higher proportion of
      children with asthma (P < .01). Logistic regression analysis showed that asthma
      increases the odds of postoperative respiratory complications to 4.4 (95%
      confidence interval, 2.13-9.0), after controlling for age, weight greater than
      the 97th percentile for age, sex, race, and medical conditions other than asthma.
      CONCLUSIONS: In children with obstructive breathing during sleep, the presence of
      asthma is associated with an increased risk of respiratory complications after
      adenotonsillectomy.

PMID- 15945560
TI  - "Early" cat ownership and the risk of sensitization and allergic rhinitis in
      Ligurian children with respiratory symptoms.
AB  - BACKGROUND: Studies on the role of cat ownership in the development of allergy
      have lead to conflicting results, probably owing to heterogeneity of the
      populations evaluated. OBJECTIVE: To evaluate the possible effect of cat
      ownership on the frequency of sensitization and asthma or rhinitis in children
      living in Liguria, Italy, who attended a pediatric clinic for respiratory
      symptoms. METHODS: We enrolled 269 consecutive school-aged children in 12 months.
      Sensitization to aeroallergens by skin prick testing and the presence of
      respiratory symptoms (ie, asthma and rhinitis) were evaluated. To analyze the
      role of different independent variables in association with respiratory symptoms
      and sensitization, a multiple logistic regression analysis was performed.
      RESULTS: Of 269 children, 81 were exposed to cats at home in the first 2 years of
      life ("early" cat owners), 65 after the first 2 years of life ("late" cat
      owners), and 123 never ("never" cat owners). Early cat ownership was
      significantly associated with a lower risk of cat sensitization compared with
      never cat ownership (adjusted odds ratio [ORadj], 0.32; 95% confidence interval
      [CI], 0.14-0.74; P = .01). Early cat ownership was also associated with a
      significantly lower risk of allergic rhinitis than late cat ownership (ORadj,
      0.43; 95% CI, 0.22-0.85) or never cat ownership (ORadj, 0.51; 95% CI, 0.28-0.92).
      No differences in the frequency of asthma were found among the 3 groups (P = .74)
      CONCLUSIONS: Cat ownership in early childhood can play an important role in
      preventing sensitization to cat and in lowering the frequency of allergic
      rhinitis, at least in children with the characteristics of the population
      studied.

PMID- 15945559
TI  - Evaluation of the utility of atopy patch testing, skin prick testing, and total
      and specific IgE assays in the diagnosis of cow's milk allergy.
AB  - BACKGROUND: Information on the utility of atopy patch testing (APT) in the
      diagnosis of food allergy is derived from studies of children with atopic
      dermatitis. OBJECTIVE: To evaluate the usefulness of APT in the diagnosis of
      cow's milk allergy (CMA) and to determine interleukin 4 and interferon-gamma
      production by peripheral blood mononuclear cells. METHODS: Thirty-seven children
      (median age, 11 months) with suspected CMA who had a variety of symptoms that
      involved many organ systems were evaluated using double-blind placebo-controlled
      food challenges (DBPCFCs), and the performances of milk specific IgE, skin prick
      testing (SPT), and APT were determined. To search for a possible relationship
      between the diagnostic tests and the TH1/TH2 immune response, we measured
      interferon-gamma and interleukin 4 levels in the supernatants of peripheral blood
      mononuclear cell cultures. RESULTS: Seventeen children with positive DBPCFC
      results and 6 with a history of anaphylaxis were diagnosed as having CMA. The
      combined use of APT and SPT had a sensitivity of 100% and a negative predictive
      value of 100% but a specificity of 50% and a positive predictive value of 76%.
      The addition of milk specific IgE assays to APT and SPT did not improve these
      values. Pattern of cytokine secretion was not associated with APT positivity or a
      specific response to DBPCFC. CONCLUSIONS: Atopy patch testing may be a useful
      adjunct to SPT in excluding CMA in children who have allergic manifestations
      other than atopic dermatitis. However, DBPCFCs are still necessary in the
      presence of positive test results.

PMID- 15945561
TI  - Antigen-IgE desensitization in signal transducer and activator of transcription 6
      deficient mast cells by suboptimal doses of antigen.
AB  - BACKGROUND: Rapid administration of suboptimal antigen induces transient
      unresponsiveness in patients with IgE antibodies to beneficial medications, but
      the molecular mechanisms of desensitization are poorly understood. Mast cells
      (MCs) have been implicated as the target cells. OBJECTIVE: To establish a
      physiologic model of IgE-antigen desensitization using mouse bone marrow-derived
      MCs (mBMMCs) from wild-type and signal transducer and activator of transcription
      6 (STAT6)-deficient mice. METHODS: The mBMMCs were sensitized with dinitrophenyl
      (DNP) IgE or trinitrophenyl (TNP) IgE and activated with DNP/TNP-human serum
      albumin. For desensitization, suboptimal doses of DNP/TNP-human serum albumin
      were administered at fixed intervals. RESULTS: Desensitized mBMMCs failed to
      respond to an optimal dose of antigen, indicating successful desensitization.
      Desensitization was time dependent, with 5 minutes of antigen exposure being
      optimal. Resensitization with DNP-IgE did not reverse the process. The
      desensitized cells were responsive to calcium ionophore and phorbol myristate
      acetate. Thus, the desensitization reaction alters an early event in the high
      affinity IgE receptor (FcepsilonRI)-dependent signaling pathway in a nontoxic
      manner. The mBMMCs from STAT6-null mice could not be desensitized by suboptimal
      doses of antigen. CONCLUSIONS: Mast cells can be rendered unresponsive by rapid
      administration of suboptimal doses of antigen in the presence of calcium, similar
      to in vivo desensitizations. The STAT6-null mBMMCs cannot be desensitized,
      providing the first molecular target in this inhibitory process.

PMID- 15945562
TI  - Evaluation and impact of chronic cough: comparison of specific vs generic quality
      of-life questionnaires.
AB  - BACKGROUND: Chronic cough is a common condition that has a significant impact on
      health-related quality of life (HRQoL). OBJECTIVE: To investigate whether chronic
      cough is associated with adverse psychological and physical effects on quality of
      life (QoL) using different HRQoL questionnaires. METHODS: Forty patients were
      recruited for the study. The diagnostic workup was mainly based on the pathogenic
      triad in chronic cough: postnasal drip syndrome, asthma, and gastroesophageal
      reflux disease. The HRQoL was evaluated with the cough-specific quality-of-life
      questionnaire (CQLQ), Leicester Cough Questionnaire (LCQ), Medical Outcomes Study
      36-Item Short-Form Health Survey (SF-36), and Hospital Anxiety and Depression
      Scale. RESULTS: Symptom scores were significantly correlated with the CQLQ and
      LCQ (beta = .415 and beta = -.272, respectively) but not with the SF-36. A
      statistically significant difference was found in all questionnaires, except the
      physical component summary domain of the SF-36, after specific therapy.
      Correlation between the 2 specific HRQoL questionnaires was moderate to high when
      pretreatment and posttreatment scores were compared (r = -0.42 and r = -0.60).
      Concurrent validity of the LCQ was higher than the CQLQ when compared with the SF
      36 domains. The effect size of each specific QoL questionnaire was 1 or higher
      after treatment, whereas it was much less in the SF-36. There was no change in
      depression with treatment despite anxiety. Posttreatment symptom scores were
      related with anxiety (r > 0.40) CONCLUSIONS: Because HRQoL is important to
      patients, a cough-specific HRQoL instrument, either the CQLQ or LCQ, should be
      routinely used to optimally evaluate the impact of cough on patients and to
      evaluate the efficacy of cough-modifying agents.

PMID- 15945563
TI  - Isolation and identification of an 11S globulin as a new major allergen in
      mustard seeds.
AB  - BACKGROUND: Although mustard seed allergy has been largely reported during the
      preceding 20 years, currently only 2 allergens, Sin a 1 and Bra j 1, have been
      identified. OBJECTIVE: To improve the characterization of the allergenic profile
      of yellow mustard seeds by reporting the identification and biochemical
      characterization of an 11S globulin as a new major allergen. METHODS: Mustard
      seed proteins were separated using size exclusion and ion-exchange
      chromatographic columns, sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis, and 2-dimensional polyacrylamide gel electrophoresis. Separation
      of different polypeptide chains was achieved by reverse-phase high-performance
      liquid chromatography. Mass spectrometry after tryptic digestion and Edman
      degradation were used to determine amino acid sequences of peptides. IgE binding
      assays were performed with 13 serum samples from mustard allergic patients in
      immunoblotting and enzyme-linked immunosorbent inhibition assays. RESULTS: A
      protein of 51 kDa was recognized as a major allergen by patients allergic to
      mustard and called Sin a 2. The allergen was dissociated in 2 chains of 36 and 23
      kDa, which also bound IgE. N-terminal end and internal amino acid sequences
      allowed identification of the new allergen as a seed storage 11S globulin
      belonging to the Cupin super family. Purified allergen was able to inhibit the
      IgE binding of sera from allergic patients to mustard seeds extract in up to 55%
      of the responses. CONCLUSIONS: An 11S globulin storage protein has been isolated
      and identified as a novel major allergen of mustard seeds.

PMID- 15945564
TI  - Hypersensitivity to airborne spitting cobra snake venom.
AB  - BACKGROUND: Although the cytolytic, neurotoxic, and hemolytic actions of snake
      venoms are well known, the ability of airborne inhaled snake venom of the
      spitting cobra to induce asthma in snake handlers has not been reported.
      OBJECTIVE: To report the allergenicity of inhaled snake venom in a snake handler
      who developed increasing hypersensitivity to airborne venom, produced by spitting
      cobras during public demonstrations. METHODS: Serum samples were obtained from 2
      handlers (our study patient and another snake handler who reported developing
      wheezing when handling spitting cobras), and desiccated venom was obtained from 9
      species to which the handlers were exposed. Serum from an asymptomatic and
      nonatopic snake handler exposed to the same snake species was used as a control.
      Phosphate-buffered saline extracts were prepared from the desiccated venom,
      proteins in the venom extracts were separated by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition
      enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross
      reactivity. RESULTS: The study patient had never been previously bitten by a
      cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by
      inhalation of salbutamol. The patient had developed IgE antibodies to 9 different
      snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63
      kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms
      in the different species was also confirmed by 50% inhibition of IgE binding in
      an ELISA by preincubation with unrelated species. Life-threatening sensitivity of
      the patient was sustained after a long period of avoidance. CONCLUSIONS: We
      propose that aerosolized snake venom be considered a new potential source of
      allergens that may result in anaphylaxis on subsequent exposure. Further studies
      of the development of specific IgE sensitization following snakebites and the
      risks of such sensitization should be conducted on snake handlers, particularly
      those who demonstrate the spitting species.

PMID- 15945565
TI  - Deer ked-induced occupational allergic rhinoconjunctivitis.
AB  - BACKGROUND: Deer keds (elk fly) have not previously been described as a cause of
      respiratory or conjunctival sensitization. OBJECTIVE: To report a case of IgE
      mediated allergic rhinoconjunctivitis from occupational exposure to deer ked.
      METHODS: Skin prick testing (SPT) was performed with pollens, animal danders,
      mites, molds, and deer ked. The serum deer ked-specific IgE level was examined in
      ImmunoSpot and radioallergosorbent test assays, and deer ked IgE-binding
      fractions and their specificities were examined in immunoblot and immunoblot
      inhibition assays. Nasal provocation testing (NPT) and conjunctival provocation
      testing (CPT) were performed to detect the association between deer ked
      sensitization and rhinoconjunctival symptoms. Both SPT and NPT were performed
      with deer ked whole-body extract, whereas CPT was performed with deer ked wing.
      RESULTS: The results of SPT, NPT, and CPT were positive for deer ked. In
      laboratory tests, serum deer ked-specific IgE antibodies were demonstrated in
      radioallergosorbent test and ImmunoSpot assays. In immunoblot, IgE-binding bands
      were demonstrated at 17, 33, 70, and 85 kDa, which were clearly inhibited with
      deer ked extract but not with the control extract. CONCLUSIONS: Occupational IgE
      mediated rhinoconjunctival allergy to deer ked was confirmed in this patient.

PMID- 15945567
TI  - [Illusion and reality].

PMID- 15945568
TI  - [Improving mobility in aging: physical training prevents accidental falls].

PMID- 15945566
TI  - Practice parameter for the diagnosis and management of primary immunodeficiency.

PMID- 15945569
TI  - [Excellent wound management with SondoFIX. A new, highly effective system for
      wound healing with infection barrier].

PMID- 15945570
TI  - [Drug therapy in the elderly: limiting to the essentials].

PMID- 15945571
TI  - [Pain management in the elderly--1: Recognizing and understanding the etiologies
      of pain].

PMID- 15945572
TI  - [Emergency deception in nursing patients with dementia: Mrs. Meier, telephone!"].

PMID- 15945573
TI  - [Strategies for nursing patients with dementia: "Isolation is horrible for those
      who are affected" (interview by Katrin Balzer)].

PMID- 15945574
TI  - [Nursing care of demented patients in the nursing home: "Everything is so quiet
      here")].

PMID- 15945575
TI  - [Validation therapy for managing patients with dementia: more than a management
      philosophy].

PMID- 15945576
TI  - [Snoezelen in dementia: disco in the nursing home or sensible therapeutic
      offering?].

PMID- 15945577
TI  - [ReduFix--a study of reducing physical restraint: preventing risk of injury].

PMID- 15945578
TI  - [Nutrition at the end of life--PEG for patients with dementia: caregivers can
      assume a central role in the decision process].

PMID- 15945579
TI  - [Massage for preventing decubitus ulcer? 1: Guidelines are still not adequately
      integrated into general practice].

PMID- 15945580
TI  - [Coaching for residential leadership--2: Integrating personal goals with those of
      the organization].

PMID- 15945581
TI  - [From case to case: at home with Mrs. K].

PMID- 15945582
TI  - [Students educate students: welcome change or more?].

PMID- 15945583
TI  - [Assessment center--a suitable method for student selection in nursing schools].
AB  - For a valid selection of applicants it is necessary to identify the specific
      abilities and personal characteristic which are required by the profession or
      education program. Until now, the selection procedures used in nursing colleges
      are merely based on psychological knowledge regarding personnel selection and
      proved methods to diagnose the suitability for profession. To fill in this gap in
      choosing nursing students, the common selection procedures have been proved and a
      procedure using elements of Assessment Centers has been developed. Assessment
      Center methods offer several advantages both to the applicants and nursing
      colleges. Applicants can become aware of their strengths and weaknesses, and can
      use these results for their further development. On the other hand, the
      probability rises, that applicants chosen for the nursing training fulfil the
      professional requirements and will successfully pass the education program.

PMID- 15945584
TI  - Budget socks Medicaid with 10 billion dollars in cuts.

PMID- 15945586
TI  - AQA releases ambulatory quality measures.

PMID- 15945585
TI  - Health coverage slipping for employees, young adults.

PMID- 15945587
TI  - Dementia care in Asia.

PMID- 15945588
TI  - Drugs used to relieve behavioral symptoms in people with dementia or an
      unacceptable chemical cosh? Argument.
AB  - As clinicians we talk about "the best interests of our patients". How can a
      treatment which doubles the rate of cognitive decline, triples the rate of
      stroke, doubles mortality, substantially increases falls and fractures and
      reduces quality of life be beneficial, especially, as in real life, once
      neuroleptics are started they are rarely discontinued with cumulative adverse
      effects? As there is clearly no rational reason for prescribing, we need to
      consider other explanations. We would suggest the following: Therapeutic
      impotence: Doctors, especially specialists feel they need to do something, and
      prescribing a familiar drug is the easiest option. Ignorance: Doctors are either
      unaware of the substantial evidence of harm with neuroleptics or are swayed by
      slick marketing information, portraying atypical neuroleptics in an "over-safe"
      light that does not reflect the actual data. Placebo effect: If neuroleptics are
      prescribed, the majority of patients experience an improvement in BPSD symptoms.
      This reinforces the apparent value of this practice, as we like to take the
      credit for any improvements that occur. The reality is that the majority of
      people would have experienced a comparable improvement with monitoring. Bowing to
      pressure: Sometimes the pressure to respond can be great, and a prescription is
      an easy way to relieve the pressure. This is understandable, and reflects a
      similar phenomenon to that of general practioners prescribing antibiotics for
      sore throats. In neither situation does it represent good practice. Lack of
      skills to implement non-pharmacological alternatives: The main evidence for
      alternative treatment options are for therapies that by and large are not a core
      part of the physician or psychiatrist's skill-base, such as psychological
      interventions. Doctors therefore feel uncomfortable pursuing these options. Why
      for example is so little time spent on the nonpharmacological interventions that
      everyone agrees should be the first line of treatment for BPSD in people with
      dementia? It is largely assumed that the "enlightened clinician has already
      appropriately assessed and diagnosed the patient and exhausted all the possible
      environmental and behavioral interventions before resorting to the prescription
      pad." Accumulating evidence clearly indicates that the need for psychotropic
      medication is substantially reduced by proactive services or interventions which
      can provide training and promote psychological, social and environmental and
      sensory interventions. The prescription but is an easy but not an acceptable
      alternative. Over-adherence to prescribing guidance: There are pharmacological
      alternatives to neuroleptics if a prescription is needed. Although the evidence
      for the more promising alternatives needs to be developed much further, drugs
      such as cholinesterase inhibitors may offer a much less harmful alternative. The
      reluctance of clinicians to use cholinesterase inhibitors in this way is
      puzzling, and presumably is because of the culture of "guidance-prescribing" that
      has evolved around these agents. If the treatment of BPSD is to move forward, we
      need to challenge the way we have always done things, examine the evidence and
      move forward with new and flexible multi-disciplinary approaches if we are truly
      to look after the "best interests of our patients".

PMID- 15945589
TI  - A case for judicious use of risperidone and olanzapine in behavioral and
      psychological symptoms of dementia (BPSD). Favour.

PMID- 15945590
TI  - A systematic review of the scientific evidence for the efficacy of a palliative
      care approach in advanced dementia.
AB  - BACKGROUND: Patients with dementia often receive poor end-of-life care, with
      inadequate pain control and without access to the palliative care services that
      patients with cancer are offered. This has been identified as an area of need in
      recent UK. Government reports and by the Alzheimer's Society (UK). Our objective
      was to perform a systematic review of the scientific literature regarding the
      efficacy of a palliative care model in patients with dementia. METHODS: A
      systematic review was carried out to identify controlled trials that investigated
      the efficacy of palliative care in patients with dementia. Data sources included
      were Medline, EMBASE, PsycINFO, CINAHL, British Nursing Index, AMED, Cochrane
      Database of Systematic Reviews, Web of Science, Cochrane Central Register of
      Controlled Trials, International Standard Randomised Controlled Trial register,
      the NHS Economic Evaluation Database and the System for Information on Grey
      Literature in Europe. Other data was sourced from hand searches of papers
      identified on electronic databases and review articles. RESULTS: The search
      identified 30 review articles, but only four papers were eligible for full
      appraisal and only two of these met the full criteria for inclusion. These papers
      gave equivocal evidence of the efficacy for a palliative model of care in
      dementia. CONCLUSION: Despite the increased interest in palliative care for
      patients with dementia there is currently little evidence on which to base such
      an approach. This may in part be due to the ethical difficulties surrounding such
      research, prognostic uncertainty in clinicians and the lack of clear outcome
      measures for patients who are unable to express their needs or wishes. Further
      systematic research is urgently needed to educate an important and developing
      area of clinical practice.

PMID- 15945591
TI  - The differentiation of mild frontotemporal dementia from Alzheimer's disease and
      healthy aging by neuropsychological tests.
AB  - BACKGROUND: Frontotemporal dementia (FTD) is difficult to diagnose in the early
      stages and may be misdiagnosed as Alzheimer's disease (AD) or as a psychiatric
      disorder. This study aimed to investigate neuropsychological function in FTD of
      mild severity and compare it to that of mild AD and healthy control participants.
      METHODS: The study comprised 11 individuals with FTD, 29 with AD and 27 healthy
      controls. Participants completed a comprehensive neuropsychological assessment in
      which each area of cognitive function was examined with several widely used
      clinical tests. Test scores were converted to age-corrected scaled scores and
      combined to form indices for six areas of cognitive function. These indices were
      attention, psychomotor speed, memory acquisition, memory recall, executive
      function and constructional ability. RESULTS: The FTD group performed below the
      level of the controls in all areas except constructional ability. FTD and AD
      groups showed distinct patterns of neuropsychological performance. The FTD group
      showed predominantly executive dysfunction with less impaired memory function,
      while the AD group showed the opposite pattern. The capacity of the tests to
      discriminate between groups was good overall, with 90% of the total sample
      correctly classified. Predictive success for the FTD group was 64%, given a base
      rate of 16%. CONCLUSION: Administration of a comprehensive neuropsychological
      protocol including several tests of executive function allows increased certainty
      about accurate clinical diagnosis of mild FTD.

PMID- 15945592
TI  - A study of the reliability and validity of the Chinese version of the Dementia
      Rating Scale.
AB  - BACKGROUND: The present study aims to develop and validate a Chinese version of
      the Dementia Rating Scale (DRS) for use with Chinese populations in
      psychogeriatric settings. METHODS: The DRS was translated into Chinese and its
      content validity was evaluated by an 11-member expert panel. To assess
      reliability and concurrent validity, 52 subjects with dementia were recruited
      from medical and psychogeriatric settings using purposive sampling. RESULTS: With
      percentage of agreement as an indicator, 28 out of 36 items (78%) had
      satisfactory content validity. Items with a percentage of agreement below 70%
      were reviewed and modified, based on the comments of the experts. The CDRS had
      excellent test-retest and inter-rater reliability, with intraclass correlation
      coefficient (ICC) at 0.94 and 0.93 respectively. Intraclass correlation
      coefficients ranged between 0.75 and 0.89 for the subscales. The internal
      consistency of the CDRS subscale, as measured by Cronbach's a, ranged from 0.57
      to 0.82. The CDRS had high correlations with the Chinese Mini-mental State
      Examination (r = 0.80 for total score, r = 0.58 to 0.84 for subscales.
      CONCLUSIONS: The CDRS is a valid instrument for the assessment of dementia in
      Chinese-speaking subjects.

PMID- 15945593
TI  - Neuropsychiatric symptoms, functional impairment and executive ability in Thai
      patients with Alzheimer's disease.
AB  - BACKGROUND: Instrumental activities of daily living (IADL) depend on executive
      planning and procedural memory mediated by the frontal lobes. Planning and
      judgment are involved in clock drawing. Neuropsychiatric symptoms are also
      mediated by frontal lobes, and a relationship between ADL, clock drawing and
      neuropsychiatric symptoms was hypothesized. OBJECTIVE: To investigate the
      relationship between behavioral disturbances, ADL, and executive function.
      METHODS: Seventy-three Thai patients with Alzheimer's disease (AD) were
      evaluated. Neuropsychiatric symptoms and behaviors were assessed with the
      Nevropsychiatric Inventory (NPI). The Thai version of the Mini-mental State
      Examination (TMSE) was utilized as a global cognitive assessment. A clock-drawing
      test (CDT) and both category (animals) and letter (ko, so in Thai) verbal fluency
      were used as executive measures. Thai ADL scale, Barthel Index (BI), and
      Functional Assessment Questionnaire (FAQ) were ADL measures used in this study.
      RESULTS: There were statistically significant correlations between CDT and the
      frontally-mediated behaviors of agitation (r = -0.367), apathy (r = -0.273) and
      disinhibition (r = -0.247). Verbal fluency correlated with agitation (r = 
      0.341). There were significant correlations between Thai ADL scores and agitation
      (r = 0.350), apathy (r = 0.441), and disinhibition (r = 0.417). FAQ correlated
      with the same three behaviors. After controlling for TMSE, a significant
      correlation remained between Thai ADL scores and agitation (r = 0.291) and apathy
      (r = 0.342). CONCLUSIONS: We demonstrated correlations between ADL and behavioral
      changes in Thai elderly with AD. Our results emphasize the important
      relationships among behavioral changes and impaired ADL.

PMID- 15945594
TI  - Higher fat and carbohydrate intake in dementia patients is associated with
      increased blood glutathione peroxidase activity.
AB  - BACKGROUND: Mounting evidence implicates diets high in fats and processed sugars
      with increased generation of free radicals in animals. It is still not clearly
      established whether such a diet alters antioxidant balance in dementia patients,
      where an oxidative stress status may already exist. The disruption to lipid
      metabolism by oxidative stress has been recently linked to neurodegeneration and
      clinical disease. The aim of this study is to assess the relationship between
      fat, sugar, carbohydrate and caloric intake levels, and antioxidant status in
      patients with mild to moderate dementia. METHODS: The levels of 3 essential
      endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase)
      were measured in the blood of 26 dementia subjects and 26 cognitively unimpaired
      controls. Concurrently, the intake levels of relevant nutrients and dietary
      antioxidants were assessed in all subjects. RESULTS: A statistically significant
      positive association was observed in the dementia group between glutathione
      peroxidase activity and the intake of fats (r = 0.44; p = 0.023), carbohydrates
      (r = 0.46; p = 0.018), total sugars (r = 0.51; p = 0.007) and calories (r = 0.47;
      p = 0.14). The only significant association in the control group was observed
      between glutathione peroxidase and fat (r = 0.47; p = 0.015). CONCLUSION: The
      higher glutathione peroxidase activity among subjects with greater intake of
      fats, carbohydrates and sugars may represent a compensatory response to the
      additional increase in oxidative stress in dementia. Our data shed light on the
      influence of dietary intake on the oxidant-antioxidant system in mild to moderate
      dementia patients.

PMID- 15945595
TI  - Understanding burden differences between men and women caregivers: the
      contribution of care-recipient problem behaviors.
AB  - BACKGROUND: This study was carried out to determine why women caring for men
      report more burden than other caregivers, and to further examine the role of care
      recipient problem behaviors as determinants of burden. METHOD: A sample of 557
      primary caregivers of community-dwelling individuals referred to a memory clinic
      was used. All care-recipients had a diagnosis of Alzheimer's disease (NINCDS
      ADRDA). Data on care-recipient function, caregiver attributes, external supports
      and caregiver burden were obtained on the first visit. Hierarchical regression
      models were used to determine the contribution of gender, after controlling for
      care-recipient status, caregiver attributes, and external supports. RESULTS: This
      model explained 46% of the variability in caregiver "role burden", with care
      recipient problem behaviors and dependence in instrumental activities of daily
      living. The caregiver/care-recipient gender interaction explained an additional
      4% of the variance (p = 0.001); women caring for men scored 5.61 higher on the
      burden scale than other caregivers. Specific problem behaviors (e.g., anger) were
      more problematic for women caregivers than men. CONCLUSION: These results
      indicate that the experience of men and women caregivers may be different despite
      seemingly identical circumstances, and highlight the need for interventions
      geared to the specific needs of women caregivers.

PMID- 15945596
TI  - Learning potential: a new method for assessing cognitive impairment.
AB  - BACKGROUND: In recent years, it has been claimed that learning potential (also
      called cognitive plasticity or rehabilitation potential) may be a good predictor
      of the course of cognitive impairment and the process of dementia. The basic
      objective of this research program is to test the extent to which the "Battery of
      Learning Potential for Assessing Dementia" (BEPAD) discriminates healthy people
      from those diagnosed with Mild Cognitive Impairment (MCI) and with Alzheimer's
      Disease (AD). METHODS: Two hundred people: 100 healthy elders (51 women, 49 men,
      mean age: 73.13), 50 diagnosed with MCI (30 women, 20 men, mean age: 74.89), and
      50 diagnosed with mild AD (36 women, 14 men, mean age: 75.07). Learning potential
      was assessed through dynamic assessment (or testing-the-limits), using
      experimental test-training-post-test, a form of evaluation closely related to
      functional or stress testing in medicine. In several previous studies the BEPAD
      was developed, with four tasks: visuo-spatial, verbal recall (including delayed
      verbal recall), executive control and verbal fluency. For all of these tasks,
      training procedures were developed, converting them into learning potential
      tests. RESULTS AND CONCLUSIONS: All "dynamic" or learning scores (post-test)
      discriminate better healthy, MCI and AD subjects than all static or pre-test
      scores. A total of 89% of cases are correctly classified by the BEPAD: 95.7% of
      the healthy subjects, 90.6% of AD patients, and 71.1% of the MCI individuals were
      correctly classified.

PMID- 15945597
TI  - Your diagnosis? Aneurysmal bone cyst.
AB  - The etiology of aneurysmal bone cysts is uncertain, but they may originate as a
      localized arteriovenous malformation. These benign lesions can be primary or
      occur secondary to an underlying lesion. The majority of patients who present
      with aneurysmal bone cysts are younger than age 20 years. One half of lesions
      occur within the long bones and one third involve the spine. Most flat bone
      lesions, approximately 10%, occur in the pelvis. Fluid-fluid levels are common on
      CT and MRI but are not pathognomonic. Although aneurysmal bone cyst is benign,
      there may be aggressive clinical and imaging features. Treatment for aneurysmal
      bone cyst is surgical curettage, intraoperative adjuvant therapy, and bone
      grafting of the lesion. The prognosis following treatment is very good, although
      10% to 20% of cases are reported to recur.

PMID- 15945598
TI  - Is rigid fixation of the fibula indicated in tibial plafond fractures?

PMID- 15945599
TI  - A new guide for condylar blade-plate on distal femoral fractures.
AB  - This article presents a new guide used to reduce the risk of malalignment
      following distal femoral fracture fixation with a 95 degrees angled blade plate.

PMID- 15945600
TI  - The 2-0 Ethilon test.
AB  - Tight closure, which is a sign of ischemia secondary to tension, can lead to
      tissue necrosis. This article describes a simple and reliable test to help avoid
      excessive tension during skin closure.

PMID- 15945601
TI  - Optimizing antiplatelet and anticoagulant agents in the perioperative orthopedic
      surgery patient.

PMID- 15945602
TI  - Lateral patella dislocation associated with an irreducible posterolateral knee
      dislocation: literature review.
AB  - Posterolateral dislocations involve significant injury to the medial structures
      of the knee, therefore particular attention should be paid to repairing the
      medial patella stabilizers at the time of open reduction.

PMID- 15945603
TI  - Use of constrained acetabular liners in total hip arthroplasty.
AB  - The use of constrained acetabular liners is indicated when soft-tissue tensioning
      techniques such as femoral neck lengthening, component repositioning, and use of
      lateralized acetabular liner are ineffective. It is most commonly used as a
      salvage procedure in revision situations. However, a locking acetabular insert
      may be used for primary THAs in patients with joint or soft-tissue laxity,
      neuromuscular disease, or intraoperative instability. In addition to the
      described commercially available liners, several manufacturers will provide
      customized components on request.

PMID- 15945604
TI  - Reinforced iliotibial tenodesis for chronic anterolateral instability of the
      knee: a 6-year follow-up.
AB  - Reinforced iliotibial tenodesis is an extra-articular procedure to eliminate
      anterolateral instability of an anterior cruciate ligament-deficient knee. The
      procedure carries a low complication rate and offers an easy rehabilitation
      program. This study evaluated the use of reinforced iliotibial tenodesis in a
      select group of 52 patients with a mean age of 41 years (range: 38-50 years).
      Obese patients, professional athletes, and patients with more complex injuries
      (eg, concomitant posterior cruciate or medial collateral ligament injuries) were
      excluded. Results are encouraging after a mean follow-up of 6 years (range: 2-10
      years). Although 24 patients had a positive anterior drawer or Lachman test, none
      had a positive pivot test. In addition, all patients reported giving way was
      eliminated after surgery.

PMID- 15945605
TI  - Quantitative morphology of the scapula: normal variation of the superomedial
      scapular angle, and superior and inferior pole thickness.
AB  - This study examined the normal variation of the superomedial scapular angle and
      the thickness of the superior and inferior scapular borders. Scapulae of 53
      cadaver shoulders were dissected free from all soft tissue. A line was drawn from
      the most superior to the most inferior point on each scapula, and the scapulae
      were cut along this line to obtain cross sections. The supero-medial scapular
      angle (alpha) was measured with a goniometer from the cross section as a ABC:
      through the inferior tip (A), base of the spine (B), and superior tip (C).
      Superior and inferior pole thickness was measured with a digital caliper from the
      thickest portions on the cross section of the poles. Average superomedial angle
      was 139 degrees +/- 6 degrees (range: 125 degrees - 156 degrees). Average
      thickness for the superior and inferior poles was 3.9 +/- 0.9 mm (range: 2.1 -
      8.3 mm) and 7.5 +/- 1.5 mm (range: 4 - 11 mm), respectively. The thickness of
      both superior and inferior poles was significantly different between male and
      female specimens (P < .05), with male scapulae having the higher values.

PMID- 15945606
TI  - The use of controlled-release versus scheduled oxycodone in the immediate
      postoperative period following total joint arthroplasty.
AB  - This prospective study examined whether better pain control could be achieved in
      the first 48 hours after joint arthroplasty with controlled-release oxycodone
      compared to scheduled oxycodone with acetaminophen. In the study group,
      controlled-release oxycodone was administered on the day of surgery and was
      continued during patients' hospital stay. The study group then was compared to a
      previous group in which effective pain control was obtained with around-the-clock
      oxycodone with acetaminophen. Findings indicated controlled-release oxycodone did
      not provide better pain control compared to scheduled oxycodone with
      acetaminophen in the first 48 hours following total joint arthroplasty.

PMID- 15945607
TI  - Surgical treatment modalities for lower-extremity iatrogenic nerve lesions.
AB  - Thirty-six patients with lower-extremity iatrogenic nerve injury were treated
      with neurolysis (23), direct nerve coaption (1), and nerve grafting (12)
      depending on the nature, duration, and degree of nerve injury. Seventeen (74%) of
      23 patients presenting with motor nerve injury achieved motor function against
      resistance. In 24 (80%) of 30 patients with sensory nerve involvement, at least
      some superficial sensory function was restored. Surgeons should be familiar with
      clinical and electroneurophysiological tests for early diagnosis of iatrogenic
      nerve injuries to allow early intervention for maximum nerve recovery.

PMID- 15945608
TI  - Scoliosis due to nonosteogenic fibroma of the L2 lamina.

PMID- 15945609
TI  - Minocycline-induced black bone disease.

PMID- 15945610
TI  - Bilateral radial head fractures with elbow dislocation.

PMID- 15945611
TI  - Effects of magnesium sulphate on leptin-dependent platelet aggregation: an ex
      vivo study.
AB  - Magnesium sulphate has well known antiplatelet properties. Its effect on leptin
      dependent platelet aggregation has not been studied previously. Thus, we
      performed this ex vivo study to investigate whether magnesium sulphate is able to
      inhibit leptin-dependent aggregation of human platelets. We obtained platelet
      rich plasma (PRP) from venous blood samples of 16 healthy male volunteers, and we
      measured ADP-induced platelet aggregation in the presence of leptin alone (5-500
      ng/mL) or leptin and magnesium sulphate (0.25-8 mM). Platelet pre-incubation with
      leptin led to a significant and dose-dependent increase in ADP-induced platelet
      aggregation. Magnesium sulphate was able to inhibit the pro-aggregating effect of
      leptin in a dose-dependent manner. The inhibitory effect was apparent at 1 mM of
      magnesium sulphate concentration (% maximal aggregation=38.1 +/- 12.2) and
      reached its maximum at 8 mM (% maximal aggregation=20.0 +/- 7.8). Our results
      demonstrate that leptin-dependent platelet aggregation is inhibited by magnesium
      sulphate in a dose-dependent manner. It seems conceivable that the blocking of
      hydrolysis of phosphoinositide and of intracellular calcium mobilization by
      magnesium sulphate may be involved in these findings.

PMID- 15945613
TI  - Magnesium depletion with hypo- or hyper- function of the biological clock may be
      involved in chronopathological forms of asthma.
AB  - Asthma is a chronic, inflammatory disorder of the airways leading to airflow
      limitation. Its worldwide rise, mainly in developed countries, is a matter of
      concern. Nocturnal asthma (NA) frequently occurs and concerns two thirds of
      asthmatics. But, it remains controversial whether NA is a distinct entity or is a
      manifestation of more severe asthma. Generally, it is considered as an
      exacerbation of the underlying pathology. The pathological mechanisms most likely
      involve endogenous circadian rhythms with pathological consequences on both
      respiratory inflammation and hyperresponsiveness. A decrease in blood and tissue
      magnesium levels is frequently reported in asthma and often testifies to a true
      magnesium depletion. The link with magnesium status and chronobiology are well
      established. The quality of magnesium status directly influences the Biological
      Clock (BC) function, represented by the suprachiasmatic nuclei and the pineal
      gland. Conversely, BC dysrythmias influence the magnesium status. Two types of
      magnesium deficits must be clearly distinguished: deficiency corresponding to an
      insufficient intake which can be corrected through mere nutritional Mg
      supplementation and depletion due to a dysregulation of the magnesium status
      which cannot be corrected through nutritional supplementation only, but requires
      the more or less specific correction of the dysregulation mechanisms. Both in
      clinical and in animal experiments, the dysregulation mechanisms of magnesium
      depletion associate a reduced magnesium intake with various types of stress
      including biological clock dysrhythmias. The differenciation between Mg depletion
      forms with hyperfunction of BC (HBC) and forms with hypofunction of BC (hBC) is
      seminal and the main biological marker is melatonin (MT) production alteration.
      We hypothesize that magnesium depletion with HBC or hBC may be involved in
      chronopathological forms of asthma. Nocturnal asthma would be linked to HBC,
      represented by an increase in MT levels. The corresponding clinical forms
      associate diverse expressions of nervous hypoexcitability such as depression,
      cluster headaches, dyssomnia, mainly advanced sleep phase syndrome, some clinical
      forms of chronic fatigue syndrome and of fibromyalgia. The main comorbidities are
      depression and/or asthenia. They take place during the night or the "bad" seasons
      (autumn and winter) when sunshine is at a minimum. The corresponding
      chronopathological therapy relies on bright light phototherapy sometimes with
      additional psychoanaleptics. Conversely, asthma forms linked to hBC are less
      frequently studied as a whole and present a decrease in MT levels. They associate
      various signs of nervous hyperexcitability such as anxiety, diurnal cephalalgia
      (mainly migraine), dyssomnia, mainly delayed sleep phase syndrome, and some
      clinical forms of chronic fatigue syndrome and of fibromyalgia. The treatment
      relies on diverse forms of "darkness therapy", possibly with the help of some
      psycholeptics. Finally, the treatment of asthma involves the maintenance of a
      standard dosing schedule of anti-asthma drugs, a balanced magnesium intake and
      the appropriate treatment of the chronopathological disorders.

PMID- 15945612
TI  - Relationship between magnesium levels in drinking water and sudden infant death
      syndrome.
AB  - The possible association between the risk of death from sudden infant death
      syndrome (SIDS) and the levels of magnesium in drinking water from municipal
      supplies was investigated in a matched case-control study in Taiwan.
      Characteristics for all SIDS deaths (501 cases) among Taiwan residents from 1988
      through 1997 were compared with those of people who died from other causes (501
      controls). The levels of magnesium in the drinking water of these residents were
      determined from data obtained from the Taiwan Water Supply Corporation (TWSC).
      The controls were pair-matched to the SIDS cases by sex, month and year of birth.
      The results of our study show that there is a significant trend towards a
      decreased risk of SIDS with increasing magnesium levels in drinking water.

PMID- 15945615
TI  - Simple model for ac ionic conduction in solids.
AB  - We present a model for the ac conduction in ionically conducting solids that
      takes into account, in a simple way, the interaction between carriers. The
      Coulomb force forms an "ionic atmosphere" that exerts a restoring force on a
      central ion, whose motion corresponds to an overdamped oscillator. We consider
      the effect of the relaxation of the ionic atmosphere by introducing an additional
      equation for the displacement of the potential toward the particle position. The
      general behavior of the ac conductivity can be understood in terms of two types
      of motions: motion of the bound ion at high frequencies determined by microscopic
      friction, and a much slower motion coupled to the surrounding carriers relaxation
      at low frequencies.

PMID- 15945614
TI  - The importance of magnesium status in the pathophysiology of mitral valve
      prolapse.
AB  - Idiopathic mitral valve prolapse (IMVP) refers to the systolic displacement of
      one or both mitral leaflets into the left atrium, with or without mitral
      regurgitation. It is one of the most common forms of cardiac abnormalities among
      young people, especially in women. IMVP usually appears to be a benign condition
      and even capable of recovery. In a minority of cases IMVP may predispose to
      complications. The data suggest an autosomal dominant inheritance of IMVP that
      exhibits both sex- and age-dependent penetrance with variable expressivity and
      genetic heterogeneity. IMVP appear to be one form or aspect of latent tetany due
      to magnesium deficit (MDLT). The prevalence, latent nature, and symptomatology of
      these two conditions appear to be strictly similar. Primary magnesium (Mg)
      deficit may result from Mg deficiency (insufficient Mg intake) and Mg depletion
      (excessive urinary Mg loss). Constitutional factors (e.g. HLA-B35, type A
      behavior pattern) should be considered in the aetiology of Mg deficit (MD). MD
      may cause abnormal fibrosis, abnormalities in collagen synthesis as well as in
      the myocardium, capable of inducing mitral apparatus dyskinesia. MD is a part of
      a picture of metabolic abnormalities, alteration of immune and autonomic nervous
      systems, cardiac arrhythmias and thromboembolic phenomena in IMVP. Laboratory
      evaluation must involve plasma Mg, erythrocyte Mg, calcemia, calciuria, and daily
      magnesuria. Normal plasma Mg concentration does not rule out the diagnosis of
      primary chronic MD. The diagnosis of MD requires the oral Mg load test.
      Correction of symptomatology by this oral physiological Mg load (5 mg/kg/day) is
      the best proof that it was due to Mg deficiency. Mg therapy is essential and
      specific for IMVP. In the majority of cases MD is due to Mg depletion and the
      oral Mg supplementation must be combined with Mg-sparing diuretics or
      physiological doses of vitamin D. Partial "Mg analogues" (beta-blockers,
      verapamil, phenytoin) may prove to be useful in some cases.

PMID- 15945616
TI  - Real-time monitoring of the origination of multimacroion domains in a
      polyelectrolyte solution.
AB  - First real-time monitoring of the origination of multimacroion domains in an
      initially homogeneous polyelectrolyte solution was performed. Domains were
      generated by pH-induced increase of macroion charge in solution of
      poly(methacrylic acid). Monitoring was performed by static and dynamic light
      scatterings, in which scattering contributions from individual polyions and
      growing multimacroion domains were separated, such that amplitudes of both modes
      were expressed in absolute units. Kinetic results also yield new information
      regarding the nature of multimacroion domains.

PMID- 15945617
TI  - Coulomb explosion of ammonia clusters induced by intense nanosecond laser at 532
      and 1064 nm: wavelength dependence of the multicharged nitrogen ions.
AB  - The Coulomb explosion of ammonia clusters induced by nanosecond laser field with
      intensity in the range of 10(10)-10(12) W cm(-2) and wavelength of 532 and 1064
      nm has been studied. N2+ and N3+ ions are the main multicharged ions at 532 nm,
      while He-like N5+ ion is the domain multicharged ion at 1064 nm.

PMID- 15945618
TI  - Probing the ultrafast nuclear motion in CS2 2+ in intense laser fields.
AB  - The temporal evolution of the nuclear wave packet of CS2 2+ formed in an intense
      laser field (60 fs, 0.13 PW/cm2) is traced in real time by the pump-and-probe
      technique combined with coincidence momentum imaging of the Coulomb explosion
      process, CS2 3+-->S+ + C+ + S+. The momentum correlations among the fragment ions
      obtained as a function of the pump-probe time delay between 133 fs to 3 ps reveal
      that the nuclear wave packet in CS2 2+ evolves not only along the anti-symmetric
      stretching coordinate to yield S+ and CS+ but also along the symmetric stretching
      coordinate leading to the simultaneous breaking of the two C-S bonds. The
      contribution from two different electronic states having bent and linear-type
      geometrical configurations is identified in the wave packet motion along the
      bending coordinate of CS2 2+.

PMID- 15945619
TI  - Statistical mechanical theory for steady state systems. II. Reciprocal relations
      and the second entropy.
AB  - The concept of second entropy is introduced for the dynamic transitions between
      macrostates. It is used to develop a theory for fluctuations in velocity, and is
      exemplified by deriving Onsager reciprocal relations for Brownian motion. The
      cases of free, driven, and pinned Brownian particles are treated in turn, and
      Stokes' law is derived. The second entropy analysis is applied to the general
      case of thermodynamic fluctuations, and the Onsager reciprocal relations for
      these are derived using the method. The Green-Kubo formulas for the transport
      coefficients emerge from the analysis, as do Langevin dynamics.

PMID- 15945620
TI  - Approximate ab initio energies by systematic molecular fragmentation.
AB  - A scheme is introduced for generating a hierarchy of molecular fragmentations by
      which the total electronic energy can be approximated from the energies of the
      fragments. Higher levels in the hierarchy produce molecular fragments of larger
      size and approximate the total electronic energy more reliably. A correction to
      account for nonbonded interactions is also presented. The accuracy of the
      approach is tested for a number of examples, and shown to be essentially
      independent of the level of ab initio theory employed. The computational cost
      increases linearly with the size of the molecule.

PMID- 15945621
TI  - Optimal dynamic discrimination of similar quantum systems with time series data.
AB  - Optimal dynamic discrimination (ODD) was proposed [Li et al., J. Phys. Chem. B
      106, 8125 (2002)] as a paradigm for discriminating noninteracting similar quantum
      systems in a mixture. This paper extends the ODD concept to optimize a laser
      control pulse for guiding similar quantum systems such that each exhibits a
      distinct time series signal for maximum discrimination. The use of temporal data
      addresses various experimental difficulties, including noise in the laser pulse,
      signal detection errors, and finite time resolution in the signal. Simulations of
      ODD with time series data are presented to explore these effects. It is found
      that the use of an optimally chosen control pulse can significantly enhance the
      discrimination quality. The ODD technique is also adapted to the case where the
      sample contains an unknown background species.

PMID- 15945622
TI  - Exchange-hole dipole moment and the dispersion interaction.
AB  - A simple model is presented in which the instantaneous dipole moment of the
      exchange hole is used to generate a dispersion interaction between nonoverlapping
      systems. The model is easy to implement, requiring no electron correlation (in
      the usual sense) or time dependence, and has been tested on various atomic and
      molecular pairs. The resulting C6 dispersion coefficients are remarkably
      accurate.

PMID- 15945623
TI  - Mechanisms of local and global molecular quantum gates and their implementation
      prospects.
AB  - We explore how the globality of quantum logic operations is ensured in the
      context of optimal control theory when qubits are encoded in vibrational
      eigenstates of different normal modes and specially shaped laser fields act as
      quantum logic operations. In a two-qubit model system, transition mechanisms for
      optimized laser fields generating single qubit flips, local NOT and global NOT
      and controlled-NOT (CNOT) gates are investigated and compared. We evaluate the
      participation of vibrational eigenstates beyond the qubit basis in the global
      gate mechanisms and how different features of CNOT and NOT gates relate to the
      characteristics of the vibrational manifold. When a non-qubit normal mode
      interacting via anharmonic resonances is introduced, neither the global gate
      mechanisms nor the optimized laser fields show a significant increase in
      complexity. Similar features of the global quantum gates in both model systems
      indicate a generality of the deduced principles. Finally, a primary concept for a
      realization of global quantum gates in an actual experiment referring to state-of
      the-art techniques is presented. The possible reconstruction of optimized laser
      fields with sequences of simple Gaussian subpulses is demonstrated and some
      critical parameters are deduced.

PMID- 15945624
TI  - Quantum kinetic energy densities: an operational approach.
AB  - We propose and investigate a procedure to measure, at least in principle, a
      positive quantum version of the local kinetic energy density. This procedure is
      based, under certain idealized limits, on the detection rate of photons emitted
      by moving atoms which are excited by a localized laser beam. The same type of
      experiment, but in different limits, can also provide other non-positive-definite
      versions of the kinetic energy density. A connection with quantum arrival time
      distributions is discussed.

PMID- 15945625
TI  - Equation-of-motion coupled-cluster methods for ionized states with an approximate
      treatment of triple excitations.
AB  - The accuracy of geometries and harmonic vibrational frequencies is evaluated for
      two equation-of-motion ionization potential coupled-cluster methods including CC3
      and CCSDT-3 triples corrections. The first two Sigma states and first Pi state of
      the N2 +, CO+, CN, and BO diatomic radicals are studied. The calculations show a
      tendency for the CC3 variant to overestimate the bond lengths and to
      underestimate the vibrational frequencies, while the CCSDT-3 variant seems to be
      more reliable. It is also demonstrated that the accuracy of such methods is
      comparable to sophisticated traditional multireference approaches and the full
      configuration interaction method.

PMID- 15945626
TI  - Finite jellium models. I. Restricted Hartree-Fock calculations.
AB  - Restricted Hartree-Fock calculations have been performed on the Fermi
      configurations of n electrons confined within a cube. The self-consistent-field
      orbitals have been expanded in a basis of N particle-in-a-box wave functions. The
      difficult one- and two-electron integrals have been reduced to a small set of
      canonical integrals that are calculated accurately using quadrature. The total
      energy and exchange energy per particle converge smoothly toward their limiting
      values as n increases; the highest occupied molecular orbital-lowest unoccupied
      molecular orbital gap and Dirac coefficient converge erratically. However, the
      convergence in all cases is slow.

PMID- 15945627
TI  - A mean field approach for molecular simulations of fluid systems.
AB  - In this paper we introduce a mean field method for simulating complex molecular
      systems like liquids and solutions. Using well-established theoretical principles
      and models, we obtained a relatively simple approach which seems to provide a
      reliable description of the bulk molecular behavior of liquid water. Moreover, we
      have applied this approach to study simple solutes in solution, like sodium and
      chloride ions and acetone. Comparison with standard simulations, performed with
      periodic boundary conditions, shows that such a mean field method can reproduce
      the same structural and thermodynamical properties at low computational costs and
      represents a valid alternative for simulating solute-solvent systems, like
      solutions of large biomolecules.

PMID- 15945628
TI  - Correlation energy extrapolation by intrinsic scaling. IV. Accurate binding
      energies of the homonuclear diatomic molecules carbon, nitrogen, oxygen, and
      fluorine.
AB  - The method of extrapolation by intrinsic scaling, recently introduced to obtain
      correlation energies, is generalized to multiconfigurational reference functions
      and used to calculate the binding energies of the diatomic molecules C2, N2, O2,
      and F2. First, accurate approximations to the full configuration interaction
      energies of the individual molecules and their constituent atoms are determined,
      employing Dunning's correlation consistent double-, triple- and quadruple zeta
      basis sets. Then, these energies are extrapolated to their full basis set limits.
      Chemical accuracy is attained for the binding energies of all molecules.

PMID- 15945629
TI  - The infrared spectrum of Au-.CO2.
AB  - The Au-.CO2 ion-molecule complex has been studied by gas phase infrared
      photodissociation spectroscopy. Several sharp transitions can be identified as
      combination bands involving the asymmetric stretch vibrational mode of the CO2
      ligand. Their frequencies are redshifted by several hundred cm(-1) from the
      frequencies of free CO2. We discuss our findings in the framework of ab initio
      and density-functional theory calculations, using anharmonic corrections to
      predict vibrational transition energies. The infrared spectrum is consistent with
      the formation of an aurylcarboxylate anion with a strongly bent CO2 subunit.

PMID- 15945630
TI  - First observation of the B1A1 state of SiH2 and SiD2 radicals by optical-optical
      double resonance spectroscopy.
AB  - The B1A1 state of SiH2 and SiD2 was observed by the optical-optical double
      resonance technique for the first time. The electronic band origin of the B state
      of SiD2 was determined to be 27 214.11 cm(-1). A very clear exclusive behavior
      depending on the even/odd value of the bending vibrational quantum number was
      observed in the spectra, representing a quasilinear behavior of the B state. The
      barrier height to linearity was estimated to be approximately 125 cm(-1) by the
      quasilinear analysis of the bending vibrational level structure of SiD2.

PMID- 15945631
TI  - Core excitation in O3 localized to one of two symmetry-equivalent chemical bonds:
      molecular alignment through vibronic coupling.
AB  - Core excitation from terminal oxygen OT in O3 is shown to be an excitation from a
      localized core orbital to a localized valence orbital. The valence orbital is
      localized to one of the two equivalent chemical bonds. We experimentally
      demonstrate this with the Auger-Doppler effect which is observable when O3 is
      core excited to the highly dissociative OT1s(-1)7a1 1 state. Auger electrons
      emitted from the atomic oxygen fragment carry information about the molecular
      orientation relative to the electromagnetic-field vector at the moment of
      excitation. The data together with analytical functions for the electron-peak
      profiles give clear evidence that the preferred molecular orientation for
      excitation only depends on the orientation of one bond, not on the total
      molecular orientation. The localization of the valence orbital "7a1" is caused by
      mixing of the valence orbital "5b2" through vibronic coupling of antisymmetric
      stretching mode with b2 symmetry. To the best of our knowledge, it is the first
      discussion of the localization of a core excitation of O3. This result explains
      the success of the widely used assumption of localized core excitation in
      adsorbates and large molecules.

PMID- 15945632
TI  - Interaction of lead atom with atmospheric dioxygen and ozone: quantic study of
      the structure and the stability of resulting Pb(On) (n=1,2,3) compounds.
AB  - Lead reaction with oxygen and ozone molecules is of a great importance for the
      study of the impact of this metal in the atmosphere medium. Stable species,
      intermediates, and transition states of possible resulting complexes have been
      studied with the three parameter hybrid B3LYP exchange-correlation DFT method,
      and coupled cluster with single, double, and triple excitation methods. Geometry,
      and spectroscopic and thermodynamic properties obtained for the different species
      are presented, discussed, and compared to available experimental data. On the
      basis of the knowledge of the thermal dissociation enthalpies and the absorbed
      wave length edges calculated for each species, we have drawn the most probable
      oxygenated complexes present in the atmosphere.

PMID- 15945633
TI  - Thermodynamics and equilibrium structure of Ne38 cluster: quantum mechanics
      versus classical.
AB  - The equilibrium properties of classical Lennard-Jones (LJ38) versus quantum Ne38
      Lennard-Jones clusters are investigated. The quantum simulations use both the
      path-integral Monte Carlo (PIMC) and the recently developed variational-Gaussian
      wave packet Monte Carlo (VGW-MC) methods. The PIMC and the classical MC
      simulations are implemented in the parallel tempering framework. The classical
      heat capacity Cv(T) curve agrees well with that of Neirotti et al. [J. Chem.
      Phys. 112, 10340 (2000)], although a much larger confining sphere is used in the
      present work. The classical Cv(T) shows a peak at about 6 K, interpreted as a
      solid-liquid transition, and a shoulder at approximately 4 K, attributed to a
      solid-solid transition involving structures from the global octahedral (Oh)
      minimum and the main icosahedral (C5v) minimum. The VGW method is used to locate
      and characterize the low energy states of Ne38, which are then further refined by
      PIMC calculations. Unlike the classical case, the ground state of Ne38 is a
      liquidlike structure. Among the several liquidlike states with energies below the
      two symmetric states (Oh and C5v), the lowest two exhibit strong delocalization
      over basins associated with at least two classical local minima. Because the
      symmetric structures do not play an essential role in the thermodynamics of Ne38,
      the quantum heat capacity is a featureless curve indicative of the absence of any
      structural transformations. Good agreement between the two methods, VGW and PIMC,
      is obtained. The present results are also consistent with the predictions by
      Calvo et al. [J. Chem. Phys. 114, 7312 (2001)] based on the quantum superposition
      method within the harmonic approximation. However, because of its approximate
      nature, the latter method leads to an incorrect assignment of the Ne38 ground
      state as well as to a significant underestimation of the heat capacity.

PMID- 15945634
TI  - Photodissociation of (SO2)m(H2O)n clusters employing femtosecond pump-probe
      spectroscopy.
AB  - A femtosecond pump-probe technique was employed to study the photodissociation
      dynamics of (SO2)m(H2O)n clusters in real time for clusters, where m=1, 2 and n
      as large as 11. The pump (excitation) step occurs through a multiphoton process
      which populates the dissociative E state as well as a lower-lying bound state of
      the sulfur dioxide (SO2) chromophore. Dissociation of the SO2 monomer occurs
      through the E state and the decay is fit to a lifetime of 230 fs. The present
      study is in agreement with our previous investigations of homogeneous (SO2)m
      clusters that have shown that cluster formation inhibits the dissociation process
      owing to a steric effect induced by the cluster environment [K. L. Knappenberger,
      Jr. and A. W. Castleman, Jr., J. Chem. Phys. 121, 3540 (2004)]. The E state
      lifetime increases sequentially as a function of cluster size to as much as 668
      fs when 11 water molecules solvate the chromophore. We have employed a method to
      compare the ratio of amplitude coefficients, which reflect a respective component
      of the mathematical fit, to determine the nature of the wave packet evolution in
      binary clusters. An increase of this ratio by as much as 440% was observed for
      large cluster sizes. A preferential ion state charge transfer, rather than
      dissociation, was observed in binary clusters. The significance of cluster size
      on evaporation processes has been investigated.

PMID- 15945635
TI  - Excited states of boron isoelectronic series from explicitly correlated wave
      functions.
AB  - The ground state and some low-lying excited states arising from the 1s2 2s2p2
      configuration of the boron isoelectronic series are studied starting from
      explicitly correlated multideterminant wave functions. One- and two-body
      densities in position space have been calculated and different expectation values
      such as <delta(r)>, <rn>, <delta(r12)>, <r12 n>, <delta(R)>, and <R(n)>, where r,
      r12, and R stand for the electron-nucleus, interelectronic, and two electron
      center of mass coordinates, respectively, have been obtained. The energetic
      ordering of the excited states and the fulfillment of the Hund's rules is
      analyzed systematically along the isoelectronic series in terms of the electron
      electron and electron-nucleus potential energies. The effects of electronic
      correlations have been systematically studied by comparing the correlated results
      with the corresponding noncorrelated ones. All the calculations have been done by
      using the variational Monte Carlo method.

PMID- 15945636
TI  - Electronic structure of 1,3,5-triaminobenzene trication and related triradicals:
      doublet versus quartet ground state.
AB  - Quantum chemical calculations have been carried out to determine the electronic
      ground state of the parent 1,3,5-triaminobenzene trication triradical
      (TAB3+,C6H9N3 3+) containing a six-membered benzene ring coupled with three
      exocyclic amino NH(*+)2 groups, each containing an unpaired electron, as the
      simplest model for high-spin polyarylamine polycations. Related triradicals,
      including the 1,3,5-trimethylenebenzene (TMB, C9H9) and its nitrogen derivatives
      such as the monocation C8H9N+, the dication C7H9N2 2+, and the neutral C8H8N,
      C7H7N2, and C6H6N3 systems containing NH groups, have also been considered.
      Results obtained using the CASSCF [multiconfigurational complete active space
      (SCF--self-consistent field)] method, with active spaces ranging from (9e/9o) to
      (15e/12o), followed by second-order perturbation theory [CASPT2 and MS-CASPT2 (MS
      -multistate)] with polarized 6-311G(d,p) and natural orbital (ANO-L) basis sets
      reveal the following: (i) both TAB3+ and TMB (D3h) have a quartet 4A"1 ground
      state with doublet-quartet 2B1-4A"1 energy gaps of 8.0+/-2.0 and 12.4+/-2.0
      kcal/mol, respectively; (ii) in the neutral N series, the quartet state remains
      the electronic ground state, irrespective of the number of N atoms, but each with
      slightly reduced gap, 11 kcal/mol for C8H8N (4A"), 10 kcal/mol for C7H7N2 (4A2),
      and 9 kcal/mol for C6H6N3 (4A2); and (iii) the ground state of monoamino cation
      and diamino dication is a low-spin doublet state (2B1 for C8H9N+ and 2A2 for
      C7H9N2 2+) and lying well below the corresponding quartet state by 10 and 12
      kcal/mol, respectively. In the monocationic and dicationic amino systems, a
      slight preference is found for the low-spin state, apparently violating Hund's
      rule. This effect is due to the splitting of the orbital energies and the
      presence of the positive charge whose delocalization strongly modifies the
      electronic distribution and some structural features. In the latter cations, the
      positive charge basically pushes unpaired electrons onto the ring forming a kind
      of distonic radical cations and thus gives a preference for a low-spin state.

PMID- 15945637
TI  - Quantum dynamics of the Li + HF --> H + LiF reaction at ultralow temperatures.
AB  - Quantum-mechanical calculations are reported for the Li+HF(v=0,1,j=0)-
      >H+LiF(v',j') bimolecular scattering process at low and ultralow temperatures.
      Calculations have been performed for zero total angular momentum using a recent
      high-accuracy potential-energy surface for the X2A' electronic ground state. For
      Li+HF(v=0,j=0), the reaction is dominated by resonances due to the decay of
      metastable states of the Li cdots,...F-H van der Waals complex. Assignment of
      these resonances has been carried out by calculating the eigenenergies of the
      quasibound states. We also find that while chemical reactivity is greatly
      enhanced by vibrational excitation, the resonances get mostly washed out in the
      reaction of vibrationally excited HF with Li atoms. In addition, we find that at
      low energies, the reaction is significantly suppressed due to the less-efficient
      tunneling of the relatively heavy fluorine atom.

PMID- 15945638
TI  - Generation of potential energy curves for the X1Sigma(+)g, B1Delta(+)g, and
      B'1Sigma(+)g states of C2 using the effective valence shell Hamiltonian method.
AB  - Calculations of the ground and excited state potential energy curves of C2 using
      the third-order effective valence Hamiltonian (Hv3rd) method are benchmarked
      against full configuration interaction and other correlated single-reference
      perturbative and nonperturbative theories. The large nonparallelity errors (NPEs)
      exhibited even by state-of-art coupled cluster calculations through perturbative
      triples indicate a serious deficiency of these single-reference theories. The Hv
      method, on the other hand, produces a much reduced NPE, rendering it a viable
      approximate many-body method for accurately determining global ground and excited
      state potential energy curvessurfaces.

PMID- 15945639
TI  - A time-dependent polarizable continuum model: theory and application.
AB  - This work presents an extention of the polarizable continuum model to explicitly
      describe the time-dependent response of the solvent to a change in the solute
      charge distribution. Starting from an initial situation in which solute and
      solvent are in equilibrium, we are interested in modeling the time-dependent
      evolution of the solvent response, and consequently of the solute-solvent
      interaction, after a perturbation in this equilibrium situation has been switched
      on. The model introduces an explicit time-dependent treatment of the polarization
      by means of the linear-response theory. Two strategies are tested to account for
      this time dependence: the first one employs the Debye model for the dielectric
      relaxation, which assumes an exponential decay of the solvent polarization; the
      second one is based on a fitting of the experimental data of the solvent complex
      dielectric permittivity. The first approach is simpler and possibly less accurate
      but allows one to write an analytic expression of the equations. By contrast, the
      second approach is closer to the experimental evidence but it is limited to the
      availability of experimental data. The model is applied to the ionization process
      of N,N-dimethyl-aniline in both acetonitrile and water. The nonequilibrium free
      energy profile is studied both as a function of the solvent relaxation coordinate
      and as a function of time. The solvent reorganization energy is evaluated as
      well.

PMID- 15945640
TI  - The eighth virial coefficient of four- and five-dimensional hard hyperspheres.
AB  - The eighth virial coefficient for hard hyperspheres is calculated by Monte Carlo
      techniques. It is found that B8/B(7)2=0.000 274+/-0.000 014 and -0.000 115+/
      0.000 012 in four and five dimensions, respectively. The results are in good
      agreement with the findings of Clisby and McCoy (e-print arXiv:cond-mat0410511),
      and confirm that B8 is negative in five dimensions.

PMID- 15945641
TI  - Poiseuille flow to measure the viscosity of particle model fluids.
AB  - The most important property of a fluid is its viscosity, it determines the flow
      properties. If one simulates a fluid using a particle model, calculating the
      viscosity accurately is difficult because it is a collective property. In this
      article we describe a new method that has a better signal to noise ratio than
      existing methods. It is based on using periodic boundary conditions to simulate
      counter-flowing Poiseuille flows without the use of explicit boundaries. The
      viscosity is then related to the mean flow velocity of the two flows. We apply
      the method to two quite different systems. First, a simple generic fluid model,
      dissipative particle dynamics, for which accurate values of the viscosity are
      needed to characterize the model fluid. Second, the more realistic Lennard-Jones
      fluid. In both cases the values we calculated are consistent with previous work
      but, for a given simulation time, they are more accurate than those obtained with
      other methods.

PMID- 15945642
TI  - Anomalous features of the kinetics of subdiffusion-assisted bimolecular
      reactions.
AB  - Some specific features of the kinetics of subdiffusion-assisted bimolecular
      reactions are analyzed in detail with the use of the non-Markovian stochastic
      Liouville equation (SLE) recently derived within the continuous time random walk
      approach. The SLE allows for describing important peculiarities of the reactions:
      Slow long time behavior of the kinetics, nonanalytical dependence of the reaction
      rate on the reactivity of particles, the onset of quasistatic regime
      independently of particle mobility in the case long-range reactivity, strong
      manifestation of fluctuation kinetics showing itself in very slow reaction
      kinetics at long times, etc.

PMID- 15945643
TI  - The hydrogen bond in ice probed by soft x-ray spectroscopy and density functional
      theory.
AB  - We combine photoelectron and x-ray absorption spectroscopy with density
      functional theory to derive a molecular orbital picture of the hydrogen bond in
      ice. We find that the hydrogen bond involves donation and back-donation of charge
      between the oxygen lone pair and the O-H antibonding orbitals on neighboring
      molecules. Together with internal s-p rehybridization this minimizes the
      repulsive charge overlap of the connecting oxygen and hydrogen atoms, which is
      essential for a strong attractive electrostatic interaction. Our joint
      experimental and theoretical results demonstrate that an electrostatic model
      based on only charge induction from the surrounding medium fails to properly
      describe the internal charge redistributions upon hydrogen bonding.

PMID- 15945644
TI  - Analysis of one-dimensional pure-exchange NMR experiments for studying dynamics
      with broad distributions of correlation times.
AB  - One-dimensional (1D) exchange NMR experiments can elucidate the geometry, time
      scale, memory, and heterogeneity of slow molecular motions (1 ms-1 s) in solids.
      The one-dimensional version of pure-exchange (PUREX) solid-state exchange NMR,
      which is applied to static samples and uses the chemical shift anisotropy as a
      probe for molecular motion, is particularly promising and convenient in
      applications where site resolution is not a problem, i.e., in systems with few
      chemical sites. In this work, some important aspects of the 1D PUREX experiment
      applied to systems with complex molecular motions are analyzed. The influence of
      intermediate-regime (10 micros-1 ms) motions and of the distribution of
      reorientation angles on the pure-exchange intensity are discussed, together with
      a simple method for estimating the activation energy of motions occurring with a
      single correlation time. In addition, it is demonstrated that detailed
      information on the motional geometry can be obtained from 1D PUREX spectral line
      shapes. Experiments on a molecular crystal, dimethyl sulfone, confirm the
      analysis quantitatively. In two amorphous polymers, atactic polypropylene (aPP)
      and polyisobutylene (PIB), which differ only by one methyl group in the repeat
      unit, the height of the normalized exchange intensity clearly reveals a striking
      difference in the width of the distribution of correlation times slightly above
      the glass transition. The aPP shows the broad distribution and Williams-Landel
      Ferry temperature dependence of correlation times typical of polymers and other
      "fragile" glass formers. In contrast, the dynamics in PIB occur essentially with
      a single correlation time and exhibits Arrhenius behavior, which is more typical
      of "strong" glass formers; this is somewhat surprising given the weak
      intermolecular forces in PIB.

PMID- 15945645
TI  - Investigation of the excited-state absorption of a Ru dioxolene complex by the Z
      scan technique.
AB  - We investigated nonlinear absorption of picosecond laser pulses in a Ru complex
      [{Ru(bipy)2}2L][PF6] using the open-aperture Z-scan technique. Experiments were
      performed in a spectral region of moderate linear absorption (lambda=532 nm,
      sigmag=0.65 x 10(-16) cm(-2)). We observed a transition from reverse saturable
      absorption to saturable absorption when the excitation intensity was higher than
      50 GW/cm2. To determine the population level kinetics, a model based on three-
      and four-level systems was considered, and the rate equations solved taking into
      account the propagation equation of the laser pulse inside the sample. Fitting of
      the experimental data allows extraction of the excited-states absorption cross
      sections and lifetimes.

PMID- 15945646
TI  - Shear softening and structure in a simulated three-dimensional binary glass.
AB  - Three-dimensional model binary glasses produced by quenching from a range of
      liquid temperatures were tested in shear over a range of strain rates using
      molecular-dynamics techniques. Tests were performed under constant volume and
      constant pressure constraints. The simulations revealed a systematic change in
      short-range order as a function of the thermal and strain history of the glass.
      While subtle signs of differences in short-range order were evident in the pair
      distribution function, three-body correlations were observed to be markedly more
      sensitive to the changes in structure. One particular structural parameter, the
      number of aligned three-atom clusters, was analyzed as a function of the degree
      of supercooling, the strain and the strain rate. The glasses quenched from the
      supercooled liquid regime were observed to contain an initially higher number of
      such clusters, and this number decreased under shear. Those quenched from high
      temperature equilibrium liquids contained lower numbers of such clusters and
      these increased or remained constant under shear. The glasses quenched from the
      supercooled liquid regime showed higher strength, more marked shear softening,
      and an increased propensity toward shear localization. The evolution of this
      structural parameter depended both on its initial value and on the imposed shear
      rate. These results were observed to hold for simulations performed under both
      constant density and constant pressure boundary conditions.

PMID- 15945647
TI  - Application of accelerated molecular dynamics schemes to the production of
      amorphous silicon.
AB  - The evolving nature of a Stillinger-Weber modeled silicon glass is studied using
      two accelerated molecular dynamics scheme, specifically, hyperdynamics and self
      guided algorithms due to Voter and due to Wu and Wang, respectively. We obtain an
      acceleration of the dynamics, a "boost," on the order of 20 without incurring any
      significant computational overhead. The validity of the results using accelerated
      methods is provided by comparison to a conventional molecular dynamics (MD)
      algorithm simulated under constant temperature conditions for more than 100 ns.
      We found that performing a sensitivity analysis of the effect of the parameters
      lambda and t1 before applying the self-guided MD scheme was important. Values of
      lambda greater than 0.1 and t1 equal to 1 ps were found to give improved
      structural evolution as compared to a conventional MD scheme. The hyperdynamics
      approximation scheme was found to be effective in obtaining boosts in the range
      of 4-12 for a small system without changing the dynamics of the evolution.
      However, for a large system size such an approach introduces significant
      perturbations to the pertinent equations of motion.

PMID- 15945648
TI  - Phase behavior of self-associating fluids with weaker dispersion interactions
      between bonded particles.
AB  - In this study, we explore the global phase behavior of a simple model for self
      associating fluids where association reduces the strength of the dispersion
      interactions between bonded particles. Recent research shows that this type of
      behavior likely explains the thermodynamic properties of strongly polar fluids
      and certain micellar solutions. Based on Wertheim's theory of associating liquids
      [M. S. Wertheim, J. Stat. Phys. 42, 459 (1986); 42, 477 (1986)], our model takes
      into account the effect that dissimilar particle interactions have on the
      equilibrium constant for self-association in the system. We find that weaker
      interactions between bonded molecules tend to favor the dissociation of chains at
      any temperature and density. This effect stabilizes a monomeric liquid phase at
      high densities, enriching the global phase behavior of the system. In particular,
      for systems in which the energy of mixing between bonded and unbonded species is
      positive, we find a triple point involving a vapor, a dense phase of chain
      aggregates, and a monomeric liquid. Phase coexistence between the vapor and the
      monomeric fluid is always more stable at temperatures above the triple point, but
      a highly associated fluid may exist as a metastable phase under these conditions.
      The presence of this metastable phase may explain the characteristic nucleation
      behavior of the liquid phase in strongly dipolar fluids.

PMID- 15945649
TI  - Structure of dense hydrogen fluoride gas from neutron diffraction and molecular
      dynamics simulations.
AB  - The gas phase of hydrogen fluoride has been investigated by neutron diffraction
      experiments at three different particle densities. All investigated states are
      within the liquid-gas coexistence region of hydrogen fluoride. From the obtained
      diffraction data we deduced information about the local structure of the gas
      phase, which consists of small agglomerates. This has been expected as liquid
      hydrogen fluoride forms the strongest hydrogen bonds known. Molecular dynamics
      simulations with a modified potential have been carried out for all
      experimentally investigated states. The results confirmed that the size of the
      formed agglomerates in the gas phase is growing with increasing density of the
      gas phase.

PMID- 15945650
TI  - Near-field optical imaging of plasmon modes in gold nanorods.
AB  - We have investigated optical properties of single gold nanorods by using an
      apertured-type scanning near-field optical microscope. Near-field transmission
      spectrum of single gold nanorod shows several longitudinal surface plasmon
      resonances. Transmission images observed at these resonance wavelengths show
      oscillating pattern along the long axis of the nanorod. The number of oscillation
      increases with decrement of observing wavelength. These spatial characteristics
      were well reproduced by calculated local density-of-states maps and were
      attributed to spatial characteristics of plasmon modes inside the nanorods.
      Dispersion relation for plasmons in gold nanorods was obtained by plotting the
      resonance frequencies of the plasmon modes versus the wave vectors obtained from
      the transmission images.

PMID- 15945651
TI  - Influence of initial oxygen coverage and magnetic moment on the NO decomposition
      on rhodium (111).
AB  - In this study, density functional theory calculations were performed to
      investigate the influence of oxygen preoccupation on the nitrogen oxide
      decomposition on rhodium. Besides gauging the coverage dependence of the
      adsorption energy of NO on the (111) rhodium facet, the influence of the initial
      oxygen coverage on the kinetics and thermodynamics of the nitrogen oxide
      decomposition reaction was also studied. The results are discussed with respect
      to a novel NOx decomposition catalyst. Furthermore, the influence of spin effects
      on the adsorption geometry as well as the adsorption energy is examined. It will
      be addressed why spin effects only have a minor influence on the behavior of NO
      on a rhodium surface.

PMID- 15945652
TI  - Polarized near-edge x-ray-absorption fine structure spectroscopy of C60
      functionalized 11-amino-1-undecane thiol self-assembled monolayer: molecular
      orientation and evidence for C60 aggregation.
AB  - Near-edge x-ray-absorption fine structure (NEXAFS) spectroscopy was adopted to
      probe the unoccupied electronic states of C60 anchored onto an organized assembly
      of 11-amino-1-undecane thiol on Au(111). The polarization dependence of the
      intensity of pi* resonance associated with C60 pi network revealed the self
      assembled monolayer (SAM) system to be oriented with an average molecular tilt
      angle of 57 degrees with respect to the surface normal. Invoking the absence of
      solid-state band dispersion effects and in comparison to solid C60 and /or 1-ML
      C60/Au(111), the electronic structure of the resulting assembly was found
      dominated by spectral position shift and linewidth and intensity changes of the
      lowest unoccupied molecular orbital (LUMO), LUMO+1, and LUMO+2 orbitals. The
      latter implied hybridization between N Pz of -NH2 group of thiolate SAM and pi
      levels of C60, resulting in a nucleophilic addition with a change in the symmetry
      of C60 from Ih to C1 in the SAM. Occurrence of a new feature at 285.3 eV in the
      NEXAFS spectrum, assigned previously to pi* graphitic LUMO, signified the
      formation of aggregated clusters, (C60)n of C60 monomer. Low tunneling current
      scanning tunneling microscopy confirmed them to be spherical and stable
      aggregates with n approximately 5.

PMID- 15945653
TI  - Molecular dynamics studies of melting and some liquid-state properties of 1-ethyl
      3-methylimidazolium hexafluorophosphate [emim][PF6].
AB  - Molecular dynamics simulations are used to study the liquid-state properties and
      melting of 1-ethyl-3-methylimidazolium hexafluorosphosphate [emim][PF6] using the
      force field of Canongia Lopes et al. [J. Phys. Chem. B 108, 2038 (2004)] and
      geometric constants from crystallographic data. The structures of the solid and
      liquid states are characterized by carbon-carbon, carbon-phosphorous, and
      phosphorous-phosphorous radial distribution functions. Spatial correlations among
      the ions are strong in the liquid state. The cohesive energy density and the
      temperature dependences of the molar volume and density of the liquid have been
      computed. The melting point is determined by equilibrating the solid-state
      supercells in which void defects have been introduced to eliminate the free
      energy barrier for the formation of a solid-liquid interface. The computed
      melting point is 375+/-10 K, which is approximately 10% higher than the
      experimental value of 333 K.

PMID- 15945654
TI  - Approximate density functionals applied to molecular quantum dots.
AB  - Recently, molecular quantum dots (MQDs) have been investigated experimentally and
      found to exhibit the Kondo effect. The Kondo effect leads to an enhancement of
      the zero-voltage conductance. Here, we study a finite cluster model of a MQD by
      means of Kohn-Sham density functional theory. Furthermore, employing an
      implementation of Landauer's formula, we calculate the conductance of the dot. We
      find that the electronic structure and the molecular conductance depend strongly
      on the exchange-correlation functional employed. While the local spin density
      approximation and the Perdew-Burke-Ernzerhof (PBE) generalized gradient
      approximation qualitatively reproduce certain features of the Kondo effect, PBE
      hybrid does not. Based on the MQD, we discuss the limitations of using density
      functional theory to model molecular electronic devices.

PMID- 15945655
TI  - A classical dynamics method for H2 diffraction from metal surfaces.
AB  - We present a discretization method that allows one to interpret measurements on
      diffraction of diatomic molecules from solid surfaces using six-dimensional (6D)
      classical trajectory calculations. It has been applied to the D2NiAl(110) and
      H2Pd(111) systems (which are models for activated and nonactivated dissociative
      chemisorption, respectively) using realistic potential energy surfaces obtained
      from first principles. Comparisons with experimental results and 6D quantum
      dynamical calculations show that, in general, the method is able to predict the
      relative intensity of the most important diffraction peaks. We therefore conclude
      that classical mechanics can be an efficient guide for experimentalists in the
      search for the most significant diffraction channels.

PMID- 15945656
TI  - The effects of confinement on the behavior of water molecules between parallel Au
      plates of (001) planes.
AB  - Molecular dynamics simulation is utilized to investigate the behavior of water
      molecules confined between two Au plates of (001) planes separated by gaps of
      24.48, 16.32, 12.24, 11.22, and 10.20 A. The simulation results indicate that the
      arrangements of the water molecules are dependent on the gap size. For the
      largest gap size, adsorption of the Au surface creates two permanent water layers
      in the vicinity of each Au plate. Furthermore, in this case, the gap size is
      sufficiently large to permit the formation of a central region within which the
      water molecules are randomly oriented in a similar manner to bulk water
      molecules. The results indicate that the orientation of the first water layer
      directly absorbed by the plate surface does not change as the gap size between
      the two Au plates is reduced. However, the orientations of the O-H bonds in the
      second water layer parallel to the surface rearrange to form hydrogen bonds
      between the water layers as the separation between the plates is decreased.
      Finally, an inspection of the variation of the self-diffusion coefficients with
      the gap size suggests that the difference between the dynamic properties of the
      water molecules in the z direction and the x-y plane decreases as the distance
      between the two Au plates increases.

PMID- 15945657
TI  - Configurational entropy of interacting particles adsorbed on one-dimensional
      channels arranged in a triangular structure.
AB  - The configurational entropy of interacting particles adsorbed on one-dimensional
      channels arranged in a triangular cross-sectional structure is studied by
      combining Monte Carlo simulation and thermodynamic integration method. Three
      different energies have been considered in the adsorption process: (1) epsilono,
      constant interaction energy between a monomer and an adsorption site; (2) wL,
      interaction energy between nearest-neighbor particles adsorbed along a single
      channel, and (3) wT, interaction energy between particles adsorbed across nearest
      neighbor channels. Special attention is devoted to the case of repulsive
      transversal interactions (wT>0), for which a rich variety of ordered phases are
      observed in the adlayer, depending on the value of the parameters kBT/wT (being
      kB the Boltzmann constant) and wL/wT. The influence of each ordered structure on
      the configurational entropy of the adlayer has been analyzed and discussed in the
      context of the lattice-gas model.

PMID- 15945658
TI  - Model study of coherent quantum dynamics of hole states in functionalized
      semiconductor nanostructures.
AB  - Functionalization of semiconductor nanocrystals can be achieved by anchoring
      organic ligands to the surface dangling bonds. The resulting surface complexes
      often introduce electronic states in the semiconductor band gap. These interband
      states sensitize the host material for photoabsorption at frequencies
      characteristic of the molecular adsorbates, leading to the well-known process of
      photoexcitation and subsequent femtosecond interfacial electron transfer. This
      paper investigates the relaxation dynamics of hole states, energetically
      localized deep in the semiconductor band gap, after the ultrafast electron-hole
      pair separation due to interfacial electron transfer. Mixed quantum-classical
      methods, based on mean-field nuclear dynamics approximated by ab initio density
      functional theory molecular dynamics simulations, reveal superexchange hole
      tunneling between adjacent adsorbate molecules in a model study of functionalized
      TiO2-anatase nanostructures. It is shown that electronic coherences can persist
      for hundreds of picoseconds under cryogenic and vacuum conditions, despite the
      partial intrinsic decoherence induced by thermal ionic motion, providing results
      of broad theoretical and experimental interest.

PMID- 15945659
TI  - Photophysics of an electrophosphorescent platinum (II) porphyrin in solid films.
AB  - We examine electronic processes in platinum (II) octaethyl porphyrin (PtOEP)
      embedded in an organic solid state matrix and in the form of vacuum-evaporated
      neat films in conjunction with potential applications of this compound to organic
      photovoltaic and electrophosphorescent devices. Absorption, photoexcitation, and
      luminescence spectra indicate the excitonic dimers to be dominant excited states,
      and their dissociation underlies the charge photogeneration process. Different
      charge separation distance (1.5 nm and 2.6 nm) in opposite charge carrier pairs
      preceding dissociation can be distinguished based on the fit of the three
      dimensional Onsager theory of geminate recombination to electromodulated
      luminescence and photoconduction measurements. The near-positive electrode
      concentrated triplet dimer excitons, produced by strongly 370 nm absorbed light
      in neat PtOEP films, are efficiently quenched by electron transfer to the metal
      (Al), generating the positive charge with an efficiency eta+ exceeding 0.15 at
      high electric fields and dominating the measured photocurrent. Their dissociation
      efficiency in the bulk, eta- (negatively biased illuminated electrode), is more
      than one order of magnitude lower than eta+. The dissociation of singlet dimer
      states dominates the bulk photogeneration process induced by the weakly-absorbed
      light at 450 nm, with comparable eta+ and eta-. The "hot excited state"
      underlying the temperature-increasing emission at 540 nm has been attributed to
      the upper excitonic component Q+ of the first absorption band Q consistent with
      the exciton concept applied successfully to the interpretation of all dimer
      underlain spectroscopic features of PtOEP samples studied.

PMID- 15945660
TI  - The structural and electronic properties of nanostructured Ce1-x-yZrxTbyO2
      ternary oxides: unusual concentration of Tb3+ and metal<-->oxygen<-->metal
      interactions.
AB  - Ceria-based ternary oxides are widely used in many areas of chemistry, physics,
      and materials science. Synchrotron-based time-resolved x-ray diffraction, x-ray
      absorption near-edge spectroscopy (XANES), Raman spectroscopy, and density
      functional calculations were used to study the structural and electronic
      properties of Ce-Zr-Tb oxide nanoparticles. The nanoparticles were synthesized
      following a novel microemulsion method and had sizes in the range of 4-7 nm. The
      Ce1-x-yZrxTbyO2 ternary systems exhibit a complex behavior that cannot be
      predicted as a simple extrapolation of the properties of Ce1-xZrxO2, Ce1-xTbxO2,
      or the individual oxides (CeO2, ZrO2, and TbO2). The doping of ceria with Zr and
      Tb induces a decrease in the unit cell, but there are large positive deviations
      with respect to the cell parameters predicted by Vegard's rule for ideal solid
      solutions. The presence of Zr and Tb generates strain in the ceria lattice
      through the creation of crystal imperfections and O vacancies. The O K-edge and
      Tb LIII-edge XANES spectra for the Ce1-x-yZrxTbyO2 nanoparticles point to the
      existence of distinctive electronic properties. In Ce1-x-yZrxTbyO2 there is an
      unexpected high concentration of Tb3+, which is not seen in TbO2 or Ce1-xTbxO2
      and enhances the chemical reactivity of the ternary oxide. Tb<-->O<-->Zr
      interactions produce a stabilization of the Tb(4f,5d) states that is responsible
      for the high concentration of Tb(3+) cations. The behavior of Ce1-x-yZrxTbyO2
      illustrates how important can be metal<-->oxygen<-->metal interactions for
      determining the structural, electronic, and chemical properties of a ternary
      oxide.

PMID- 15945661
TI  - Depletion and pair interactions of proteins in polymer solutions.
AB  - We study the depletion, pair interaction, and phase behavioral characteristics of
      proteins in polymer solutions. We use a McMillan-Mayer-like approach [W. G.
      McMillan, Jr. and J. E. Mayer, J. Chem. Phys. 13, 276 (1945)] to suggest that the
      depletion characteristics should be studied at an effective polymer concentration
      which is a function of both the average polymer and the protein concentrations.
      In the protein limit, we show that the volume of the polymer depletion layers
      exceeds the size of the proteins, leading to effective polymer concentrations
      typically in the semidilute and concentrated regimes even when the average
      polymer concentrations are in the dilute regimes. We propose an approximate
      approach that accounts for the multibody depletion overlaps, and use an accurate
      numerical solution of polymer mean-field theory to address depletion
      characteristics in these regimes which are characterized by both the importance
      of polymer interactions as well as the curvature of the proteins relative to the
      correlation length of polymers. We show that the depletion characteristics of the
      protein-polymer mixture can be quite different when viewed in this framework, and
      this can have profound consequences for the phase behavior of the mixture. Our
      theoretical predictions for the phase diagram match semiquantitatively with
      published experimental results.

PMID- 15945662
TI  - Brownian dynamics simulations of polyelectrolyte adsorption in shear flow.
AB  - Brownian dynamics simulations are used to study the adsorption of an isolated
      polyelectrolyte molecule onto an oppositely charged flat surface in the absence
      and the presence of an imposed shear flow. The polyelectrolyte is modeled as a
      freely jointed bead-rod chain where excluded volume interactions are incorporated
      by using a hard-sphere potential. The total charge along the backbone is
      distributed uniformly among all the beads, and the beads are allowed to interact
      with one another and the charged surface through screened Coulombic interactions.
      The simulations are performed by placing the molecule a fixed distance above the
      surface, and the adsorption behavior is then studied as a function of screening
      length. In the absence of an imposed flow, the chain is found to lie flat and
      extended on the adsorbing surface in the limit of weak screening, whereas in the
      limit of strong screening it desorbs from the surface and attains free-solution
      behavior. For intermediate screening, only a small portion of the chain adsorbs
      and it becomes highly extended in the direction normal to the surface. An imposed
      shear flow tends to orient the chain in the direction of flow and also leads to
      increased contact of the chain with the surface.

PMID- 15945663
TI  - Swelling of polyelectrolyte networks.
AB  - Employing molecular dynamics simulations of a coarse-grained model, the
      equilibrium swelling behavior of a cross-linked polyelectrolyte gel has been
      investigated with a bead-spring defect-free network with diamond-like topology
      under good solvent conditions and close to the theta-point, the counterions were
      treated explicitly. To examine the validity range of simple scaling arguments we
      varied the amount of charges in the system, the length of the network chains, the
      strength of the electrostatic interactions for both solvent qualities over a wide
      range of parameters. We find that classical theories only apply in the limit of
      weak electrostatics and suggest corrections based on the microscopic interplay of
      the systems' components accessible in a simulation, which model successfully our
      measured data.

PMID- 15945664
TI  - Ordering mechanism of asymmetric diblock copolymers confined between polymer
      grafted surfaces.
AB  - Using self-consistent-field calculation, we study the equilibrium morphology of
      asymmetric block copolymer melts between two brush-covered surfaces. We discuss
      systematically the morphologies formed as a function of the grafting density of
      brushes and show a series of reentrant structural transformations between the
      lamellar and hexagonal phases. Such a selection of ordered microdomains has been
      attributed to the interplay among entropy effects of stretched brushes, the
      preferential interaction of the blocks with the grafted substrate, and the bulk
      microphase-separated behavior of asymmetric copolymers. Interestingly for the
      affinitive brush-copolymer interfaces, the bulk hexagonal phase may still be
      remained due to entropy elasticity of brushes, and the frustration can be
      relieved by deforming the shape of "soft" polymer-brush surface, in contrast to
      the hard-wall cases. The result demonstrates a simple way to realize molecular
      self-assembly for confined copolymer films with well-controlled thickness and
      interfacial environment.

PMID- 15945665
TI  - Rate constants and branching ratios for the dissociative recombination of C3D(+)7
      and C4D(+)9.
AB  - Product branching ratios and thermal rate coefficients for the dissociative
      recombination of C3D(+)7 and C4D(+)9 have been measured in the ion storage ring
      CRYRING. The results for C3D(+)7 are believed to be slightly more accurate than
      those obtained earlier for C3H(+)7. Only the C-C bond breaking channels could be
      measured for C4D(+)9 and were found to be in excellent agreement with earlier
      data.

PMID- 15945666
TI  - Elimination of translational and rotational motions in nuclear orbital plus
      molecular orbital theory.
AB  - The nuclear orbital plus molecular orbital (NOMO) theory was developed in order
      to determine the nonadiabatic nuclear and electronic wave functions. This study
      presents a formulation to remove the contamination of rotational motion as well
      as translational motion in the NOMO theory. We have formulated the translation-
      and rotation-free (TRF)-NOMO theory by introducing the TRF Hamiltonian. The
      principal moment of inertia, which is the denominator in the rotational
      Hamiltonian, is expanded in a Taylor series. The zeroth-order of the Taylor
      expansion corresponds to a rigid-body rotator. The first-order terms contribute
      the coupling between the vibration and the rotation. Hartree-Fock equations have
      been derived in the framework of the TRF-NOMO theory. Numerical assessments,
      which were preformed for H2, D2, T2, mu2 (muon dimmer), and H2O, confirmed the
      importance of the TRF treatment.

PMID- 15945667
TI  - Self-consistent solution of the Dyson equation for atoms and molecules within a
      conserving approximation.
AB  - We have calculated the self-consistent Green's function for a number of atoms and
      diatomic molecules. This Green's function is obtained from a conserving self
      energy approximation, which implies that the observables calculated from the
      Green's functions agree with the macroscopic conservation laws for particle
      number, momentum, and energy. As a further consequence, the kinetic and potential
      energies agree with the virial theorem, and the many possible methods for
      calculating the total energy all give the same result. In these calculations we
      use the finite temperature formalism and calculate the Green's function on the
      imaginary time axis. This allows for a simple extension to nonequilibrium
      systems. We have compared the energies from self-consistent Green's functions to
      those of nonselfconsistent schemes and also calculated ionization potentials from
      the Green's functions by using the extended Koopmans' theorem.

PMID- 15945668
TI  - Multicanonical schemes for mapping out free-energy landscapes of single-component
      and multicomponent systems.
AB  - Multicanonical (MUCA) sampling is a powerful approach for simulating large
      domains of thermodynamic macrostate space that relies on mapping out either the
      density of states or a free energy of the system as a function of a suitable
      "order parameter." The purpose of this study is to extend and apply to more
      complex systems the method introduced in a previous paper [M. K. Fenwick and F.
      A. Escobedo, J. Chem. Phys. 120, 3066 (2004)] that uses Bennett's acceptance
      ratio method for estimating MUCA free energies. Four types of MUCA schemes are
      considered according to what order parameter is adopted and how the macrostate
      space is traversed: a la grand canonical ensemble, a la semigrand canonical
      ensemble, a la semigrand isothermal-isobaric ensemble, and a la isothermal
      isobaric ensemble. Two types of systems are studied, the first is a two-component
      Lennard-Jones mixture that exhibits a vapor-liquid transition, and the second is
      a hard-cuboid containing system that exhibits an isotropic-liquid crystalline
      transition. These systems are simulated with different MUCA schemes and the
      resulting free-energy profiles are used to determine phase-coexistence
      conditions. For the Lennard-Jones systems, it is also demonstrated that different
      types of MUCA simulations can be conveniently performed over different macrostate
      regions and the results can be subsequently pieced together into a continuous
      weighting function.

PMID- 15945669
TI  - Multidimensional quantum trajectories: applications of the derivative propagation
      method.
AB  - In a previous publication [J. Chem. Phys. 118, 9911 (2003)], the derivative
      propagation method (DPM) was introduced as a novel numerical scheme for solving
      the quantum hydrodynamic equations of motion (QHEM) and computing the time
      evolution of quantum mechanical wave packets. These equations are a set of
      coupled, nonlinear partial differential equations governing the time evolution of
      the real-valued functions C and S in the complex action, S=C(r,t) +
      iS(r,t)/Planck's over 2pi, where Psi(r,t)=exp(S). Past numerical solutions to the
      QHEM were obtained via ensemble trajectory propagation, where the required first-
      and second-order spatial derivatives were evaluated using fitting techniques such
      as moving least squares. In the DPM, however, equations of motion are developed
      for the derivatives themselves, and a truncated set of these are integrated along
      quantum trajectories concurrently with the original QHEM equations for C and S.
      Using the DPM quantum effects can be included at various orders of approximation;
      no spatial fitting is involved; there is no basis set expansion; and single,
      uncoupled quantum trajectories can be propagated (in parallel) rather than in
      correlated ensembles. In this study, the DPM is extended from previous one
      dimensional (1D) results to calculate transmission probabilities for 2D and 3D
      wave packet evolution on coupled Eckart barrier/harmonic oscillator surfaces. In
      the 2D problem, the DPM results are compared to standard numerical integration of
      the time-dependent Schrodinger equation. Also in this study, the practicality of
      implementing the DPM for systems with many more degrees of freedom is discussed.

PMID- 15945670
TI  - Gear formalism of the always stable predictor-corrector method for molecular
      dynamics of polarizable molecules.
AB  - The recently proposed always stable predictor-corrector method for molecular
      dynamics of polarizable molecules [J. Kolafa, J. Comput. Chem. 25, 335 (2004)] is
      rewritten in the Gear formalism. This equivalent form simplifies an
      implementation if the Newton equations of motion are integrated by the Gear
      method and also enables a variable integration step. Algorithms are presented for
      both the original and new versions and tested on a pair of polarizable ions
      exhibiting anharmonic vibrations.

PMID- 15945671
TI  - Fluctuation-dissipation theorem density-functional theory.
AB  - Using the fluctuation-dissipation theorem (FDT) in the context of density
      functional theory (DFT), one can derive an exact expression for the ground-state
      correlation energy in terms of the frequency-dependent density response function.
      When combined with time-dependent density-functional theory, a new class of
      density functionals results that use approximations to the exchange-correlation
      kernel fxc as input. This FDT-DFT scheme holds promise to solve two of the most
      distressing problems of conventional Kohn-Sham DFT: (i) It leads to correlation
      energy functionals compatible with exact exchange, and (ii) it naturally includes
      dispersion. The price is a moderately expensive O(N6) scaling of computational
      cost and a slower basis set convergence. These general features of FDT-DFT have
      all been recognized previously. In this paper, we present the first benchmark
      results for a set of molecules using FDT-DFT beyond the random-phase
      approximation (RPA)-that is, the first such results with fxc not equal to 0. We
      show that kernels derived from the adiabatic local-density approximation and
      other semilocal functionals suffer from an "ultraviolet catastrophe," producing a
      pair density that diverges at small interparticle distance. Nevertheless,
      dispersion interactions can be treated accurately if hybrid functionals are
      employed, as is demonstrated for He2 and HeNe. We outline constraints that future
      approximations to fxc should satisfy and discuss the prospects of FDT-DFT.

PMID- 15945672
TI  - A coherent discrete variable representation method for multidimensional systems
      in physics.
AB  - A coherent discrete variable representation (ZDVR) is proposed for constructing a
      multidimensional potential-optimized DVR basis. The multidimensional quadrature
      pivots are obtained by diagonalizing a complex coordinate operator matrix in a
      finite basis set, which is spanned by the lowest eigenstates of a two-dimensional
      reference Hamiltonian. Here a c-norm condition is used in the diagonalization
      procedure. The orthonormal eigenvectors define a collocation matrix connecting
      the localized ZDVR basis functions and the finite basis set. The method is
      applied to two vibrational models for computing the lowest bound states. Results
      show that the ZDVR method provides exponential convergence and accurate energies.
      Finally, a zeroth-order approximation method is also derived.

PMID- 15945673
TI  - Topography of molecular scalar fields. II. An appraisal of the hierarchy
      principle for electron momentum densities.
AB  - The previously observed hierarchy principle for nondegenerate critical points
      (CPs) of the electron momentum density (EMD) of molecules [Kulkarni, Gadre, and
      Pathak, Phys. Rev. A. 45, 4399 (1992)] is verified at a reliable level of theory.
      Application of Morse inequalities and the Poincare-Hopf relation to EMD leads to
      some rigorous results viz (i) for total number of CPs, NCP=3,7,11,15, ...there
      must be either a (3,+3) or a (3,-1) CP at the center of symmetry, (ii) for
      N(CP)=1,5,9,13, ...there must be either a (3,-3) or a (3,+1) CP at the center of
      symmetry. A single directional maximum on every ray, starting from p=0 has been
      observed for all the test molecules and is suggested as a working topographical
      principle in p space. This working principle is shown to satisfy the sufficiency
      condition for the hierarchy principle.

PMID- 15945674
TI  - Partial averaging and the centroid virial estimator for stereographic projection
      path-integral simulations in curved spaces.
AB  - We develop and test three different partial averaging theories for the
      stereographic projection path integral in curved spaces. Additionally, we adapt
      and test the centroid virial estimator for the kinetic energy in curved spaces.
      We tested both a confining as well as a nonconfining potential for the particle
      in a ring. All three partial averaging theories are demonstrated to converge
      linearly in the asymptotic region with k(-2)max, the number of Fourier
      coefficients. We use an error estimator to determine the optimal parameters for
      an extrapolation to infinite kmax. We verify that the centroid virial estimator
      (derived from the primitive DeWitt path-integral formula) converges to the
      kinetic energy for both confining and nonconfining potentials.

PMID- 15945675
TI  - Theory of solvent influence on reaction dynamics.
AB  - A generalization of the recently published quantum-classical approximation [A. A.
      Neufeld, J. Chem. Phys., 119, 2488 (2003)] for the purposes of reaction dynamics
      in condensed phase is presented. The obtained kinetic equations treat a solvent
      influence in a nonphenomenological way, account for the change of the free energy
      of the surrounding media, allow for different solvent dynamics in each reaction
      channel, and constitute a powerful framework for an accurate modeling of solvent
      effects, including ultrafast processes. The key features of the approach are its
      differential form, which considerably facilitates practical applications, and
      well defined wide applicability limits. The developed methodology fully accounts
      for an arbitrary long memory of the canonical bath and covers solvent-induced
      processes from a subpicosecond time scale.

PMID- 15945676
TI  - Statistical theory of nonadiabatic transitions.
AB  - Based on results of the preceding paper, and assuming fast equilibration in phase
      space to the temperature of the surrounding media compared to the time scale of a
      reaction, we formulate a statistical theory of intramolecular nonadiabatic
      transitions. A classical mechanics description of phase space dynamics allows for
      an ab initio treatment of multidimensional reaction coordinates and easy
      combination with any standard molecular dynamics (MD) method. The presented
      approach has several features that distinguishes it from existing methodologies.
      First, the applicability limits of the approach are well defined. Second, the
      nonadiabatic transitions are treated dynamically, with full account of detailed
      balance, including zero-point energy, quantum coherence effects, arbitrarily long
      memory, and change of the free energy of the bath. Compared to popular trajectory
      surface hopping schemes, our MD-based algorithm is more efficient
      computationally, and does not use artificial ad hoc constructions like a "fewest
      switching" algorithm, and rescaling of velocities to conserve total energy. The
      enhanced capabilities of the new method are demonstrated considering a model of
      two coupled harmonic oscillators. We show that in the rate regime and at moderate
      friction the approach precisely reproduces the free-energy-gap law. It also
      predicts a general trend of the reaction dynamics in the low friction limit, and
      is valid beyond the rate regime.

PMID- 15945677
TI  - Simulation of electronic and geometric degrees of freedom using a kink-based path
      integral formulation: application to molecular systems.
AB  - A kink-based path integral method, previously applied to atomic systems, is
      modified and used to study molecular systems. The method allows the simultaneous
      evolution of atomic and electronic degrees of freedom. The results for CH4, NH3,
      and H2O demonstrate this method to be accurate for both geometries and energies.
      A comparison with density functional theory (DFT) and second-order Moller-Plesset
      (MP2) level calculations show the path integral approach to produce energies in
      close agreement with MP2 energies and geometries in close agreement with both DFT
      and MP2 results.

PMID- 15945678
TI  - A pulsed-field ionization photoelectron secondary ion coincidence study of the
      H2+ (X,upsilon+=0-15,N+=1)+He proton transfer reaction.
AB  - The endothermic proton transfer reaction, H2+(upsilon+)+He-->HeH+ +
      H(DeltaE=0.806 eV), is investigated over a broad range of reactant vibrational
      levels using high-resolution vacuum ultraviolet to prepare reactant ions either
      through excitation of autoionization resonances, or using the pulsed-field
      ionization-photoelectron-secondary ion coincidence (PFI-PESICO) approach. In the
      former case, the translational energy dependence of the integral reaction cross
      sections are measured for upsilon+=0-3 with high signal-to-noise using the guided
      ion beam technique. PFI-PESICO cross sections are reported for upsilon+=1-15 and
      upsilon+=0-12 at center-of-mass collision energies of 0.6 and 3.1 eV,
      respectively. All ion reactant states selected by the PFI-PESICO scheme are in
      the N+=1 rotational level. The experimental cross sections are complemented with
      quasiclassical trajectory (QCT) calculations performed on the ab initio potential
      energy surface provided by Palmieri et al. [Mol. Phys. 98, 1839 (2000)]. The QCT
      cross sections are significantly lower than the experimental results near
      threshold, consistent with important contributions due to resonances observed in
      quantum scattering studies. At total energies above 2 eV, the QCT calculations
      are in excellent agreement with the present results. PFI-PESICO time-of-flight
      (TOF) measurements are also reported for upsilon+=3 and 4 at a collision energy
      of 0.6 eV. The velocity inverted TOF spectra are consistent with the prevalence
      of a spectator-stripping mechanism.

PMID- 15945679
TI  - Non-Born-Oppenheimer variational calculations of HT+ bound states with zero
      angular momentum.
AB  - We report fully nonadiabatic calculations of all rotationless bound states of HT+
      molecular ion (t+p+e-) carried out in the framework of the variational method. We
      show that, in all the states, except the two highest ones, the bond in the system
      can be described as covalent. In the highest two states the bond becomes
      essentially ionic and HT+ can be described as a T+H+ complex. The wave function
      of the system was expanded in terms of spherically symmetric, explicitly
      correlated Gaussian functions with preexponential multipliers consisting of
      powers of the internuclear distance. Apart from the total energies of the states,
      we have calculated the expectation values of the t-p, t-e, and p-e interparticle
      distances, their squares, and the nucleus-nucleus correlation functions.

PMID- 15945680
TI  - The role of relativity in the optical response of gold within the time-dependent
      current-density-functional theory.
AB  - We included relativistic effects in the formulation of the time-dependent current
      density-functional theory for the calculation of linear response properties of
      metals [P. Romaniello and P. L. de Boeij, Phys. Rev. B (to be published)]. We
      treat the dominant scalar-relativistic effects using the zeroth-order regular
      approximation in the ground-state density-functional theory calculations, as well
      as in the time-dependent response calculations. The results for the dielectric
      function of gold calculated in the spectral range of 0-10 eV are compared with
      experimental data reported in literature and recent ellipsometric measurements.
      As well known, relativistic effects strongly influence the color of gold. We find
      that the onset of interband transitions is shifted from around 3.5 eV, obtained
      in a nonrelativistic calculation, to around 1.9 eV when relativity is included.
      With the inclusion of the scalar-relativistic effects there is an overall
      improvement of both real and imaginary parts of the dielectric function over the
      nonrelativistic ones. Nevertheless some important features in the absorption
      spectrum are not well reproduced, but can be explained in terms of spin-orbit
      coupling effects. The remaining deviations are attributed to the underestimation
      of the interband gap (5d-6sp band gap) in the local-density approximation and to
      the use of the adiabatic local-density approximation in the response calculation.

PMID- 15945681
TI  - IR/UV and UV/UV double-resonance study of guaiacol and eugenol dimers.
AB  - Guaiacol (2-methoxyphenol) and eugenol (4-allyl-2-methoxyphenol) molecules are
      biologically active phenol derivatives with an intramolecular -OH...OCH3 hydrogen
      bond (H bond). Pulsed supersonic expansions of mixtures of either of the two
      molecules with He yield weakly bound homodimers as well as other higher-order
      complexes. A number of complementary and powerful laser spectroscopic techniques,
      including UV-UV and IR-UV double resonances, have been employed to interrogate
      the species formed in the expansion in order to get information on their
      structures and spectroscopic properties. The interpretation of the spectra of
      eugenol dimer is complex and required a previous investigation on a similar but
      simpler molecule both to gain insight into the possible structures and support
      the conclusions. Guaiacol (2-methoxyphenol) has been used for that purpose. The
      combination of the broad laser study combined with ab initio calculations at the
      Becke 3 Lee-Yang-Parr/6-31+Gd level has provided the isomer structures, the
      potential-energy wells, and shed light on the inter- and intramolecular
      interactions involved. Guaiacol homodimer has been shown to have a single isomer
      whereas eugenol dimer has at least two. The comparison between the computed
      geometries of the dimers, their respective energies, and the vibrational normal
      modes permits the identification of the spectra.

PMID- 15945682
TI  - Search for global minimum geometries for medium sized germanium clusters: Ge12
      Ge20.
AB  - We have performed an unbiased search for the global minimum geometries of small
      to-medium sized germanium clusters Gen(12< or =n< or =18) as well as a biased
      search (using seeding method) for Gen(17< or =n< or =20). We employed the basin
      hopping algorithm coupled with the plane-wave pseudopotential density functional
      calculations. For each size, we started the unbiased search with using several
      structurally very different initial clusters, or we started the biased search
      with three different seeds. Irrespective of the initial structures of clusters we
      found that the obtained lowest-energy clusters of the size n=12-16 and 18 are the
      same. Among them, the predicted global minima of Gen(12< or =n< or =16) are
      identical to those reported previously [Shvartsburg et al., Phys. Rev. Lett. 83,
      167 (1999)]. For n=17-20, we have identified two or three nearly isoenergetic low
      lying isomers (for each size) that compete for the global minimum. Nearly all the
      low-lying clusters in the size range of 12< or =n< or =20 contain the tri-caped
      trigonal prism motif and are all prolate in geometry, in agreement with the
      experiment.

PMID- 15945683
TI  - Comparative studies of the spectroscopy of CuCl2: DFT versus standard ab initio
      approaches.
AB  - The X2Pi g-2Sigma g+, X2Pi g-2Delta g, X2Pi g-2Sigma u+, X2Pi g-2Pi u transitions
      on CuCl2 have been studied using several exchange-correlation functionals from
      the various types of density functional theory (DFT) approaches like local
      density approximation (LDA), generalized gradient approximation (GGA), hybrid and
      meta-GGA. The results are compared with the experience and with those coming from
      the most sophisticated nondynamic and dynamic electronic correlation treatments
      using the same relativistic effective core potentials and especially developed
      basis sets to study the electronic structure of the five lowest states and the
      corresponding vertical and adiabatic transition energies. The calculated
      transition energies for three of the hybrid functionals (B3LYP, B97-2, and PBE0)
      are in very good agreement with the benchmark ab initio results and experimental
      figures. All of the other functionals largely overestimate the X2Pi g-2Sigma g+
      and X2Pi g-2Delta g transition energies, many of them even placing the 2Delta g
      ligand field state above the charge transfer 2Pi u and 2Sigma u+ states. The
      relative weight of the Hartree-Fock exchange in the definition of the functional
      used appears to play a key role in the accurate description of the LambdaSSigma
      density defined by the orientation of the 3d hole (sigma, pi, or delta) on Cu in
      the field of both chlorine atoms, but no simple connection of this weight with
      the quality of the spectra has been found. Mulliken charges and spin densities
      are carefully analyzed; a possible link between the extent of spin density on the
      metal for the X2Pi g state and the performance of the various functionals was
      observed, suggesting that those that lead to the largest values (close to 0.65)
      are the ones that best reproduce these four transitions. Most functionals lead to
      a remarkably low ionicity for the three ligand field states even for the best
      performing functionals, compared to the complete active space (SCF) (21, 14) ab
      initio values. These findings show that not only large variational ab initio
      calculations can produce reliable spectroscopic results for extremely complex
      systems where delicate electronic correlation effects have to be carefully dealt
      with. However, those functionals that were recently shown to perform best for a
      series of molecular properties [J. Chem. Phys. 121 3405 (2004)] are not the ones
      that produce the best transition energies for this complex case.

PMID- 15945684
TI  - Penning ionization of N2O molecules by He*(2(3,1)S) and Ne*(3P2,0) metastable
      atoms: a crossed beam study.
AB  - The energetics of [Rg... N2O]* autoionizing collision complexes (where Rg=He or
      Ne) and their dynamical evolution have been studied in a crossed beam apparatus,
      respectively, by Penning ionization electron spectroscopy (PIES) and by mass
      spectrometry (MS) techniques in the thermal energy range. The PIES spectra,
      detected by an electron energy analyzer, were recorded for both complexes at four
      different collision energies. Such spectra allowed the determination of the
      energy shifts for Penning electron energy distributions, and the branching ratios
      for the population of different electronic states and for the vibrational
      population in the molecular nascent ions. For the [Ne...N2O]* collision complex
      it was found, by MS, that the autoionization leads to the formation of N2O+, NO+,
      O+, and NeN2O+ product ions whose total and partial cross sections were measured
      in the collision energy range between 0.03 and 0.2 eV. The results are analyzed
      exploiting current models for the Penning ionization process: the observed
      collision energy dependence in the PIES spectra as well as in the cross sections
      are correlated with the nature of the N2O molecule orbitals involved in the
      ionization and are discussed in term of the Rg-N2O interaction potentials, which
      are estimated by using a semiempirical method developed in our laboratory.

PMID- 15945686
TI  - Orientation and alignment moments in two-color polarization spectroscopy.
AB  - A theoretical analysis of two-color polarization spectroscopy (TCPS) is presented
      as an extension of a previous analysis of one-color PS. Three commonly used
      schemes in which pump and probe transitions share a common level are considered.
      Diagrammatic techniques are used to isolate the photon interaction sequences that
      can contribute to the signal. A perturbation-theory analysis expressing the
      signal in terms of spherical tensor moments is applied. The analysis emphasises
      the significance of orientation and alignment tensor moments of rotational
      angular momentum and their collisional evolution. The assumed context is
      transitions between single rotational states of gas-phase molecules that
      subsequently suffer discrete collisions. The time scale of the measurements is
      assumed to be long relative to the periods of molecular motion, as would
      typically be the case for signals excited by nanosecond-pulsed lasers from
      samples at moderate pressures. The Doppler motion of the probed species is
      included, as is an analytical solution to the integration over the Maxwell
      Boltzmann distribution of velocities. The effects of nuclear hyperfine
      depolarization and velocity-changing collisions are discussed. It is shown that
      when pump- and probe-laser pulses are separated in time, TCPS creates and probes
      either orientation or alignment of rotational angular momentum in the common
      level shared by pump and probe transitions. Example simulations of one- and two
      color polarization spectroscopies are included to demonstrate the resulting
      simplification of the measured signal using TCPS. TCPS is therefore a viable
      spectroscopic technique for the determination of rotational angular momentum
      orientation and alignment relaxation rates in molecular gases, of interest
      because they are sensitive probes of inelastic collisions.

PMID- 15945685
TI  - Penning ionization of N2O molecules by He*(2(3,1)S) and Ne*(3P2,0) metastable
      atoms: theoretical considerations about the intermolecular interactions.
AB  - A theoretical investigation of the intermolecular interaction, operative in
      collision complexes of He*(2 3S1), He*(2 1S0), and Ne*(3P2,0) with N2O, is
      carried out to explain the main results of the experimental study reported in the
      preceding paper. The analysis is carried out by means of a semiempirical method
      based on the identification, modeling, and combination of the leading interaction
      components, including the effect of the selective polarization of the more
      external electronic cloud of the metastable atom in the intermolecular electric
      field. These and other crucial aspects of our approach have been quantitatively
      verified by ab initio calculations. The proposed method permits to evaluate the
      interaction at any configuration of the complexes and provides a useful and
      inexpensive representation of the intermolecular potential energy for dynamics
      studies. The main experimental findings can be rationalized taking into account
      the critical balancing between molecular orientation effects in the
      intermolecular interaction field and the ionization probability. These
      orientation effects tend to become less pronounced with increasing collision
      energy.

PMID- 15945687
TI  - Density functional approach to thermodynamics of self-assembly.
AB  - A local density functional approximation for predicting the surface
      crystallization of a thermodynamically small system under gravity is described
      and tested. Using the model of the classical soft-sphere fluid, the state
      parameters for such systems are identified. A generalized phase diagram based
      upon the scaling variables is obtained; systems with the same reduced-state
      parameters exhibit identical profiles of thermodynamic properties such as
      density, pressure, and intrinsic chemical potential, measured in the direction of
      the applied field. The point-thermodynamic approximation of Rowlinson and the
      local density approximation of the density functional formalism are found to be
      remarkably accurate. A configurational temperature is defined and shown to agree
      with the corresponding kinetic temperature for inhomogeneous systems at
      equilibrium. The structural profiles at the crystal-fluid interface are
      indicative of a mesolayer of lower density crystal, not seen in the field-free
      isobaric crystal-liquid interface.

PMID- 15945688
TI  - Multipole-multimode Floquet theory in nuclear magnetic resonance.
AB  - In this paper, we present a new analytical approach for describing the spin
      dynamics of synchronous and asynchronous time-dependent modulations in solid
      state nuclear magnetic resonance experiments. The approach, based on multimode
      Floquet theory, employs the multipole operator basis of Sanctuary for spin
      description and illustrates the time evolution in the Floquet-Liouville space
      using the effective Hamiltonians obtained from the contact (or van Vleck)
      transformation procedure. Since the Hamiltonian and the density operator are
      expressed in terms of irreducible tensor operators, extensions to higher spin
      magnitudes (I>12) and multiple spins are quite straightforward and permit
      analytical treatments for many problems. We outline the general underlying
      principles involved in this approach with a brief mention of its potential
      application in other branches of spectroscopy.

PMID- 15945689
TI  - Theory of heteronuclear decoupling in solid-state nuclear magnetic resonance
      using multipole-multimode Floquet theory.
AB  - A formal theory for heteronuclear decoupling in solid-state magic angle spinning
      (MAS) nuclear magnetic resonance experiments is presented as a first application
      of multipole-multimode Floquet theory. The method permits a straightforward
      construction of the multispin basis and describes the spin dynamics via effective
      Floquet Hamiltonians obtained using the van Vleck transformation method in the
      Floquet-Liouville space. As a test case, we consider a model three-spin system
      (I2S) under asynchronous time modulations (both MAS and rf irradiation) and
      derive effective Hamiltonians for describing the spin dynamics in the Floquet
      Liouville space during heteronuclear decoupling. Furthermore, we describe and
      evaluate the origin of cross terms between the various anisotropic interactions
      and illustrate their exact contributions to the spin dynamics. The theory
      presented herein should be applicable to the design and understanding of pulse
      sequences for heteronuclear and homonuclear recoupling and decoupling.

PMID- 15945690
TI  - Molecular dynamics of confined glucose solutions.
AB  - Silica gels containing solutions of glucose in heavy water at different
      concentrations have been prepared by a sol-gel method. Dynamical studies with
      quasielastic neutron scattering, compared with previous results on bulk
      solutions, show that the dynamics of the glucose molecules are not appreciably
      affected by the confinement, even though the gels behave macroscopically as solid
      materials. Small-angle neutron-scattering spectra on the same systems, fitted
      with a fractal model, yield a correlation length that decreases from 20 to 2.5 nm
      with increasing glucose concentration, suggesting a clustering of glucose
      molecules in concentrated solutions that is consistent with the dynamical
      measurements. These two sets of results imply that 20 nm is an upper limit for
      the scale at which the dynamics of glucose molecules in solution are affected by
      confinement.

PMID- 15945691
TI  - The inelastic hard dimer gas: a nonspherical model for granular matter.
AB  - We study a two-dimensional gas of inelastic smooth hard dimers. Since the
      collisions between dimers are dissipative, being characterized by a coefficient
      of restitution alpha<1, and no external driving force is present, the energy of
      the system decreases in time and no stationary state is achieved. However, the
      resulting nonequilibrium state of the system displays several interesting
      properties in close analogy with systems of inelastic hard spheres, whose
      relaxational dynamics has been thoroughly explored. We generalize to inelastic
      systems a recently method introduced [G. Ciccotti and G. Kalibaeva, J. Stat.
      Phys. 115, 701 (2004)] to study the dynamics of rigid elastic bodies made up of
      different spheres held together by rigid bonds. Each dimer consists of two hard
      disks of diameter d, whose centers are separated by a fixed distance a. By
      describing the rigid bonds by means of holonomic constraints and deriving the
      appropriate collision rules between dimers, we reduce the dynamics to a set of
      equations which can be solved by means of event-driven simulation. After deriving
      the algorithm we study the decay of the total kinetic energy, and of the ratio
      between the rotational and the translational kinetic energy of inelastic dimers.
      We show numerically that the celebrated Haff's homogeneous cooling law t(-2),
      describing how the kinetic energy of an inelastic hard-sphere system with a
      constant coefficient of restitution decreases in time, holds even in the case of
      these nonspherical particles. We fully characterize this homogeneous decay
      process in terms of appropriate decay constants and confirm numerically the
      scaling behavior of the velocity distributions.

PMID- 15945692
TI  - Rate processes with non-Markovian dynamical disorder.
AB  - Rate processes with dynamical disorder are investigated within a simple framework
      provided by unidirectional electron transfer (ET) with fluctuating transfer rate.
      The rate fluctuations are assumed to be described by a non-Markovian stochastic
      jump process which reflects conformational dynamics of an electron transferring
      donor-acceptor molecular complex. A tractable analytical expression is obtained
      for the relaxation of the donor population (in the Laplace-transformed time
      domain) averaged over the stationary conformational fluctuations. The
      corresponding mean transfer time is also obtained in an analytical form. The case
      of two-state fluctuations is studied in detail for a model incorporating substate
      diffusion within one of the conformations. It is shown that an increase of the
      conformational diffusion time results in a gradual transition from the regime of
      fast modulation characterized by the averaged ET rate to the regime of
      quasistatic disorder. This transition occurs at the conformational mean residence
      time intervals fixed much less than the inverse of the corresponding ET rates. An
      explanation of this paradoxical effect is provided. Moreover, its presence is
      also manifested for the simplest, exactly solvable non-Markovian model with a
      biexponential distribution of the residence times in one of the conformations.
      The nontrivial conditions for this phenomenon to occur are found.

PMID- 15945693
TI  - Colloidal electroconvection in a thin horizontal cell. I. Microscopic cooperative
      patterns at low voltage.
AB  - Applying an electric field to an aqueous colloidal dispersion establishes a
      complex interplay of forces among the highly mobile simple ions, the more highly
      charged but less mobile colloidal spheres, and the surrounding water. This
      interplay can induce a wide variety of visually striking dynamical instabilities
      even when the applied field is constant. This paper reports on the highly
      organized patterns that emerge when electrohydrodynamic forces compete with
      gravity in thin layers of charge-stabilized colloidal spheres subjected to low
      voltages between parallel-plate electrodes. Depending on the conditions, these
      spheres can form levitating clusters with morphologies ranging from tumbling
      clouds to toroidal vortex rings and to writhing labyrinths.

PMID- 15945694
TI  - Interaction of self-assembled monolayers of oligo(ethylene glycol)-terminated
      alkanethiols with water studied by vibrational sum-frequency generation.
AB  - Vibrational sum-frequency generation (VSFG) was used to investigate the
      conformational changes in self-assembled monolayers (SAMs) of (1-mercaptoundec-11
      yl) hexa(ethylene glycol) monomethylether (EG6-OMe) on gold when exposed to
      liquid water. VSFG spectra of the EG6-OMe SAMs were recorded before, during, and
      after exposure of the films to water and after a subsequent evacuation step.
      While in contact with water the entire ethylene glycol chains are found in a
      random, solvated state, after removal from the fluid water molecules remain
      absorbed only at the terminal groups of the film giving rise to distinct
      conformational changes. After evacuation, the structure of the EG6-OMe SAM
      reverts to its original state, indicating that water has been removed from the
      monolayer. Our findings support recent ab initio calculations and Monte Carlo
      simulations on the interaction of ethylene glycol-terminated monolayers with
      water.

PMID- 15945695
TI  - Detection of flexoelectric effect from 4-heptyloxy-4'-cyanobiphenyl monolayers at
      an air-water interface by Maxwell displacement current and optical second
      harmonic generation.
AB  - The flexoelectric effect of 4-heptyloxy-4'-cyanobiphenyl (7OCB) monolayers at the
      air-water interface is studied by Maxwell displacement current (MDC) and optical
      second harmonic generation measurements. Though MDC was expected to increase
      during the compression of 7OCB monolayers in L2L2' phase from the MDC theory
      developed previously, decrease of MDC was detected in these phases. This
      abnormalous phenomenon is found to be due to the quench of flexoelectric effect
      by the flow orientation of monolayers.

PMID- 15945696
TI  - Reorganization of small Co particles on Al2O3 surfaces monitored by ferromagnetic
      resonance.
AB  - Changes of the magnetic properties of ferromagnetic Co particles deposited on the
      radical31 x radical31R +/- 9 degrees reconstructed alpha-Al2O3(0001) as well as
      on a thin alumina film grown on a NiAl(110) substrate were investigated as a
      function of thermal annealing. On the thin film changes of the magnetic response
      were found above 500 K which correlates with changes in the particle size
      distribution. Annealing to 870 K leads to a permeation of the metal though the
      oxide film which causes significant changes in the ferromagnetic resonance
      response. On the alpha-Al2O3 single crystal sintering of particles requires
      temperatures above 600 K being about 100 K higher as compared to the thin alumina
      film. For large clusters intraparticle redistribution takes place already below
      600 K a phenomenon not observed for the small clusters. In addition, a
      significant dependence of the measured g values from the substrate as well as the
      thermal treatment is found which can be understood in terms of the structural
      properties of the systems.

PMID- 15945697
TI  - Reactive Monte Carlo and grand-canonical Monte Carlo simulations of the propene
      metathesis reaction system.
AB  - The influence of silicalite-1 pores on the reaction equilibria and the
      selectivity of the propene metathesis reaction system in the temperature range
      between 300 and 600 K and the pressure range from 0.5 to 7 bars has been
      investigated with molecular simulations. The reactive Monte Carlo (RxMC)
      technique was applied for bulk-phase simulations in the isobaric-isothermal
      ensemble and for two phase systems in the Gibbs ensemble. Additionally, Monte
      Carlo simulations in the grand-canonical ensemble (GCMC) have been carried out
      with and without using the RxMC technique. The various simulation procedures were
      combined with the configurational-bias Monte Carlo approach. It was found that
      the GCMC simulations are superior to the Gibbs ensemble simulations for reactions
      where the bulk-phase equilibrium can be calculated in advance and does not have
      to be simulated simultaneously with the molecules inside the pore. The confined
      environment can increase the conversion significantly. A large change in
      selectivity between the bulk phase and the pore phase is observed. Pressure and
      temperature have strong influences on both conversion and selectivity. At low
      pressure and temperature both conversion and selectivity have the highest values.
      The effect of confinement decreases as the temperature increases.

PMID- 15945698
TI  - Origin of nonlocal interactions in adsorption of polar molecules on Si(001)-2 x
      1.
AB  - Using density functional theory slab calculations, we have investigated (i) the
      origin of nonlocal interactions occurring in the adsorption of small polar
      molecules (H2O,NH3,CH3OH,CH3NH2) on the clean Si(001)-2 x 1 surface and (ii) the
      nonlocal effects on two-dimensional arrangement of adsorbates. Our results show
      the adsorption properties are significantly altered in the presence of adsorbates
      on an adjacent dimer along a row. We have identified that the coverage dependent
      behavior arises from a combination of (i) surface polarization change, (ii)
      adsorbate-induced charge delocalization, (iii) adsorbate-adsorbate repulsion, and
      (iv) hydrogen bonding. The nucleophilic-electrophilic molecular adsorption
      involves charge delocalization to neighboring dimers along a row, which in turn
      undermines molecular adsorption on the neighboring dimers. Nonlocal effects
      associated with polar interactions with neighboring dimers and adsorbates vary
      with adsorption system. While such polar interactions are unimportant in CH3OH
      adsorption, hydrogen bonding and adsorbate-adsorbate repulsion play an important
      role in determining the adsorption structures of H2O and NH3CH3NH2, respectively.
      In addition, the electrostatic attraction with the buckled-up Si atoms of
      adjacent dimers contributes to stabilization of H2O, NH3, and CH3NH2 adsorption.
      We also discuss kinetic effects on two-dimensional ordering of adsorbates, in
      conjunction with surface phase transition and adsorption-dissociation rates.

PMID- 15945699
TI  - n-alkanes on MgO(100). I. Coverage-dependent desorption kinetics of n-butane.
AB  - High-quality temperature-programmed desorption (TPD) measurements of n-butane
      from MgO(100) have been made for a large number of initial butane coverages (0
      3.70 ML, ML-monolayers) and a wide range of heating ramp rates (0.3-10 K/s). We
      present a TPD analysis technique which allows the coverage-dependent desorption
      energy to be accurately determined by mathematical inversion of a TPD spectrum,
      assuming only that the preexponential factor (prefactor) is coverage independent.
      A variational method is used to determine the prefactor that minimizes the
      difference between a set of simulated TPD spectra and corresponding experimental
      data. The best fit for butane desorption from MgO is obtained with a prefactor of
      10(15.7+/-1.6) s(-1). The desorption energy is 34.9+/-3.4 kJ/mol at 0.5-ML
      coverage, and varies with coverage approximately as
      Ed(theta)=34.5+0.566theta+8.37 exp(-theta/0.101). Simulations based on these
      results can accurately reproduce TPD experiments for submonolayer initial
      coverages over a wide range of heating ramp rates (0.3-10 K/s). Advantages and
      limitations of this method are discussed.

PMID- 15945700
TI  - n-alkanes on MgO(100). II. Chain length dependence of kinetic desorption
      parameters for small n-alkanes.
AB  - Coverage-dependent desorption-kinetics parameters are obtained from high-quality
      temperature-programmed desorption data for seven small n-alkane molecules on
      MgO(100). The molecules, CNH2N+2 (N=1-4,6,8,10), were each studied for a set of
      29 initial coverages at a heating ramp rate of 0.6 K/s as well as at a set of
      nine ramp rates in the range of 0.3-10.0 K/s. The inversion analysis method with
      its least-squares preexponential factor (prefactor) optimization discussed in the
      accompanying article is applied to these data. This method allows for accurate
      determination of prefactors and coverage-dependent desorption energies. The
      prefactor for desorption increases dramatically with chain length from 10(13.1)
      to 10(19.1) s(-1) over the range of N=1-10. We show that this increase can be
      physically justified by considering the increase in rotational entropy available
      to the molecules in the gaslike transition state for desorption. The desorption
      energy increases with chain length as Ed(N)=6.5+7.1N, which implies an
      incremental increase of 7.1+/-0.2 kJ/mol per CH2.

PMID- 15945701
TI  - Nonequilibrium Monte Carlo simulation of lattice block copolymer chains subject
      to oscillatory shear flow.
AB  - This paper has extended nonequilibrium Monte Carlo (MC) approach to simulate
      oscillatory shear flow in a lattice block copolymer system. Phase transition and
      associated rheological behaviors of multiple self-avoiding chains have been
      investigated. Stress tensor has been obtained based upon sampled configuration
      distribution functions. At low temperatures, micellar structures have been
      observed and the underlying frequency-dependent rheological properties exhibit
      different initial slopes. The simulation outputs are consistent with the
      experimental observations in literature. Chain deformation during oscillatory
      shear flow has also been revealed. Although MC simulation cannot account for
      hydrodynamic interaction, the highlight of our simulation approach is that it
      can, at small computing cost, investigate polymer chains simultaneously at
      different spatial scales, i.e., macroscopic rheological behaviors, mesoscopic
      self-assembled structures, and microscopic chain configurations.

PMID- 15945702
TI  - van der Waals interaction of simple, parallel polymers.
AB  - We study the mutual interactions of simple parallel polymers within the framework
      of density-functional theory (DFT). As the conventional implementations of DFT do
      not treat the long-range dispersion [van der Waals (vdW)] interactions, we
      develop a systematic correction scheme for the nonlocal energy contribution of
      the polymer interaction at the intermediate to the asymptotic separations. We
      primarily focus on the three polymers, polyethylene, isotactic polypropylene, and
      isotactic polyvinylchloride, but the scheme presented applies also more generally
      to other simple polymers. From first-principle calculations we extract the
      geometrical and electronic structures of the polymers and the local part of their
      interaction energy, as well as the static electric response. The dynamic
      electrodynamic response is modeled on the basis of these static calculations,
      from which the nonlocal vdW interaction of the polymers is extracted.

PMID- 15945703
TI  - Modeling a tethered polymer in Poiseuille flow.
AB  - We investigate the behavior of a tethered polymer in Poiseuille flow using a
      multiscale algorithm. The polymer, treated using molecular dynamics, is coupled
      to a solvent modeled by the stochastic rotation algorithm, a particle-based
      Navier-Stokes integrator. The expected series of morphological transitions of the
      polymer: sphere to distorted sphere to trumpet to stem and flower to rod are
      recovered, and we discuss how the polymer extension depends on the flow velocity.
      Backflow effects cause an effective increase in viscosity, which appears to be
      primarily due to the fluctuations of the free end of the polymer.

PMID- 15945704
TI  - Molecular diffusion in liquid crystals and chiral discrimination. I. Theory.
AB  - The possibility of using cholesteric phases for discriminating enantiomers of a
      chiral solute on the basis of their different transport properties, motivates the
      investigation of the translational diffusion by taking fully into account the
      roto-translational coupling. In this article a detailed theoretical analysis is
      presented for the transport properties evaluated according to the asymptotic
      limit of the mean-squared displacement. A general relation is derived for the
      transport coefficients, having as main ingredients the mean-field potential due
      to the mesophase, and the diffusion tensor with its purely translational and
      rotational components, and with the blocks describing the roto-translational
      coupling. The application of the theory to nematic phases shows that the roto
      translational coupling generates a dynamical contribution reducing the transport
      coefficients evaluated by taking into account only the translational diffusion
      components in the center of diffusion. The theory is also specialized to a
      cholesteric phase with a given helical pitch for the director arrangement, in a
      form which is suitable for calculations of model systems of chiral solutes to be
      presented in a forthcoming paper.

PMID- 15945705
TI  - The colloidal force of bead-spring chains in a good solvent.
AB  - A recently developed density functional theory (DFT) for tethered bead-spring
      chains is used to investigate colloidal forces for the good solvent case. A
      planar surface of tethered chains is opposed to a bare, hard wall and the force
      exerted on the bare wall is calculated by way of the contact density. Previously,
      the case of large wall separation was investigated. The density profiles of the
      unperturbed chains, in that case, were found to be neither stepfunctions nor
      parabolas and were shown to accurately predict computer simulation results. In
      the present paper, the surface forces that result from the distortion of these
      density profiles at finite wall separation is studied. The resulting force
      function is analyzed for varying surface coverages, wall separations, and chain
      lengths. The results are found to be in near quantitative agreement with the
      scaling predictions of Alexander [S. Alexander, J. Phys. (Paris) 38, 983 (1977)]
      when the layer thickness is "correctly" defined. Finally, a hybrid Alexander-DFT
      theory is suggested for the analysis of experimental results.

PMID- 15945707
TI  - Density-matrix renormalization-group algorithms with nonorthogonal orbitals and
      non-Hermitian operators, and applications to polyenes.
AB  - We describe the theory and implementation of two extensions to the density-matrix
      renormalization-group (DMRG) algorithm in quantum chemistry: (i) to work with an
      underlying nonorthogonal one-particle basis (using a biorthogonal formulation)
      and (ii) to use non-Hermitian and complex operators and complex wave functions,
      which occur naturally in biorthogonal formulations. Using these developments, we
      carry out ground-state calculations on ethene, butadiene, and hexatriene, in a
      polarized atomic-orbital basis. The description of correlation in these systems
      using a localized nonorthogonal basis is improved over molecular-orbital DMRG
      calculations, and comparable to or better than coupled-cluster calculations,
      although we encountered numerical problems associated with non-Hermiticity. We
      believe that the non-Hermitian DMRG algorithm may further become useful in
      conjunction with other non-Hermitian Hamiltonians, for example, similarity
      transformed coupled-cluster Hamiltonians.

PMID- 15945708
TI  - An improved density matrix functional by physically motivated repulsive
      corrections.
AB  - An improved density matrix functional [correction to Buijse and Baerends
      functional (BBC)] is proposed, in which a hierarchy of physically motivated
      repulsive corrections is employed to the strongly overbinding functional of
      Buijse and Baerends (BB). The first correction C1 restores the repulsive exchange
      correlation (xc) interaction between electrons in weakly occupied natural
      orbitals (NOs) as it appears in the exact electron pair density rho(2) for the
      limiting two-electron case. The second correction C2 reduces the xc interaction
      of the BB functional between electrons in strongly occupied NOs to an exchange
      type interaction. The third correction C3 employs a similar reduction for the
      interaction of the antibonding orbital of a dissociating molecular bond. In
      addition, C3 applies a selective cancellation of diagonal terms in the Coulomb
      and xc energies (not for the frontier orbitals). With these corrections, BBC
      still retains a correct description of strong nondynamical correlation for the
      dissociating electron pair bond. BBC greatly improves the quality of the BB
      potential energy curves for the prototype few-electron molecules and in several
      cases BBC reproduces very well the benchmark ab initio potential curves. The
      average error of the self-consistent correlation energies obtained with BBC3 for
      prototype atomic systems and molecular systems at the equilibrium geometry is
      only ca. 6%.

PMID- 15945709
TI  - The calculation of excitation energies based on the relativistic two-component
      zeroth-order regular approximation and time-dependent density-functional with
      full use of symmetry.
AB  - In the present work, we propose a relativistic time-dependent density-functional
      theory (TDDFT) based on the two-component zeroth-order regular approximation and
      a noncollinear exchange-correlation (XC) functional. This two-component TDDFT
      formalism has the correct nonrelativistic limit and affords the correct threefold
      degeneracy of triplet excitations. The relativistic TDDFT formalism is
      implemented into the AMSTERDAM DENSITY FUNCTIONAL program package for closed
      shell systems with full use of double-group symmetry to reduce the computational
      effort and facilitate the assignments. The performance of the formalism is tested
      on some closed-shell atoms, ions, and a few diatomic molecules containing heavy
      elements. The results show that the fine structure of the excited states for most
      atoms and ions studied here can be accurately accounted for with a proper XC
      potential. For the excitation energies of the molecules studied here, the present
      formalism shows promise and the error encountered is comparable to that of
      nonrelativistic TDDFT calculations on light elements.

PMID- 15945710
TI  - Rosenbluth-sampled nonequilibrium work method for calculation of free energies in
      molecular simulation.
AB  - We present methods that introduce concepts from Rosenbluth sampling [M. N.
      Rosenbluth and A. W. Rosenbluth, J. Chem. Phys. 23, 356 (1955)] into the
      Jarzynski nonequilibrium work (NEW) free-energy calculation technique [C.
      Jarzynski, Phys. Rev. Lett. 78, 2690 (1997)]. The proposed hybrid modifies the
      way steps are taken in the NEW process. With it, each step is selected from a
      range of alternatives, with bias given to steps that contribute the least work.
      The definition of the work average is modified to account for the bias. We
      introduce two variants of this method, lambda-bias sampling and configuration
      bias sampling, respectively; a combined lambda- and configuration-bias method is
      also considered. By reducing the likelihood that large nonequilibrated work
      values enter the ensemble average, the Rosenbluth sampling aids in remedying
      problems of inaccuracy of the calculation. We demonstrate the performance of the
      proposed methods through a model system of N independent harmonic oscillators.
      This model captures the difficulties involved in calculating free energies in
      real systems while retaining many tractable features that are helpful to the
      study. We examine four variants of this model that differ qualitatively in the
      nature of their phase-space overlap. Results indicate that the lambda-bias
      sampling method is most useful for systems with entropic sampling barriers, while
      the configuration-bias methods are best for systems with energetic sampling
      barriers. The Rosenbluth-sampling schemes yield much more accurate results than
      the unbiased nonequilibrium work method. Typically the accuracy can be improved
      by about an order of magnitude for a given amount of sampling; this improvement
      translates into two or more orders of magnitude less sampling required to obtain
      a given level of accuracy, owing to the generally slow convergence of the NEW
      calculation when the inaccuracy is large.

PMID- 15945711
TI  - Non-Fickian interdiffusion of dynamically asymmetric species: a molecular
      dynamics study.
AB  - We use molecular dynamics combined with dissipative particle dynamics to
      construct a model of a binary mixture where the two species differ only in their
      dynamic properties (friction coefficients). For an asymmetric mixture of slow and
      fast particles we study the interdiffusion process. The relaxation of the
      composition profile is investigated in terms of its Fourier coefficients. While
      for weak asymmetry we observe Fickian behavior, a strongly asymmetric system
      exhibits clear indications of anomalous diffusion, which occurs in a crossover
      region between cases I (Fickian) and II (sharp front moving with constant
      velocity), and is close to the case II limit.

PMID- 15945712
TI  - Improved importance sampling distribution for rate constant calculation.
AB  - An efficient method to compute the thermal rate constant for rare events within
      the correlation function C(t) approach is presented. This method, which is based
      on a modification of the sampling function used to evaluate the dynamical
      correlation function C(t), can be applied to high-dimensional systems having a
      rough energy landscape without previous knowledge on the transition states
      location. In this work, the sampling of a Boltzmann-like distribution for the
      linear momenta with a lower inverse temperature (beta(*)=1/kT(*)) than the
      correct one (beta=1/kT) is proposed as a way to increase the number of reactive
      trajectories. The mismatch between the beta(*) and beta distributions is then
      corrected by a reweighting procedure which allows one to obtain the exact
      correlation function C(t). The efficiency of this scheme in computing the rate of
      a particle jumping across the barrier of a simple 2D double well potential is
      improved by a factor 4-25 depending on the relative value of the original beta
      and modified beta(*) temperatures. When merged with the "puddle potential" method
      [S. A. Corcelli, J. A. Rohman, and J. C. Tully, J. Chem. Phys., 118, 1085
      (2003)], the new importance sampling function improves the efficiency of the
      correlation function approach by a factor 16-800 with respect to the unbiased
      sampling. To test the method in a more challenging case, the previous model
      system was extended by adding six harmonically restrained particles, each one
      interacting with the diffusing particle. This model introduces both the
      possibility of energy exchange and a rougher energy landscape. The new sampling
      function alone is found to produce an improvement in efficiency of, at least, an
      order of magnitude when compared with the unbiased case; when merged with the
      puddle potential method, a 400-fold saving in computer time is found.

PMID- 15945713
TI  - Calculation of electric-field gradients based on higher-order generalized Douglas
      Kroll transformations.
AB  - In this paper, the calculation of electric-field-like properties based on higher
      order Douglas-Kroll-Hess (DKH) transformations is discussed. The electric-field
      gradient calculated within the Hartree-Fock self-consistent field framework is
      used as a representative property. The properties are expressed as an analytic
      first derivative of the four-component Dirac energy and the nth-order DKH energy,
      respectively. The differences between a "forward" transformation of the
      relativistic energy or the "back transformation" of the wave function is
      discussed in some detail. Detailed test calculations were carried out on the
      electric-field gradient at the halogen nucleus in the series HX (X=F,Cl,Br,I,At)
      for which extensive reference data are available. The DKH method is shown to
      reproduce (spin-free) four-component Dirac-Fock results to an accuracy of better
      than 99% which is significantly closer than previous DKH studies. The
      calculations of both the Hamiltonian and the property operator are shown to be
      essentially converged after the second-order transformation, even for elements as
      heavy as At. In addition, we have obtained results within the density-functional
      framework using the DKHZ and zeroth-order regular approximation (ZORA) methods.
      The latter results included picture-change effects at the scalar relativistic
      variant of the ZORA-4 level and were shown to be in quantitative agreement with
      earlier results obtained by van Lenthe and Baerends. The picture-change effects
      are somewhat smaller for the ZORA method compared to DKH. For heavier elements
      significant differences in the field gradients predicted by the two methods were
      found. Based on comparison with four-component Dirac-Kohn-Sham calculations, the
      DKH results are more accurate. Compared to the spin-free Dirac-Kohn-Sham
      reference values, the ZORA-4 formalism did not improve the results of the ZORA
      calculations.

PMID- 15945714
TI  - Variational calculation of vibrational linear and nonlinear optical properties.
AB  - A variational approach for reliably calculating vibrational linear and nonlinear
      optical properties of molecules with large electrical and/or mechanical
      anharmonicity is introduced. This approach utilizes a self-consistent solution of
      the vibrational Schrodinger equation for the complete field-dependent potential
      energy surface and, then, adds higher-level vibrational correlation corrections
      as desired. An initial application is made to static properties for three
      molecules of widely varying anharmonicity using the lowest-level vibrational
      correlation treatment (i.e., vibrational Moller-Plesset perturbation theory). Our
      results indicate when the conventional Bishop-Kirtman perturbation method can be
      expected to break down and when high-level vibrational correlation methods are
      likely to be required. Future improvements and extensions are discussed.

PMID- 15945715
TI  - Ab initio calculation of bowl, cage, and ring isomers of C20 and C20-.
AB  - High-level ab initio calculations have been carried out to reexamine relative
      stability of bowl, cage, and ring isomers of C(20) and C(20)(-). The total
      electronic energies of the three isomers show different energy orderings,
      strongly depending on the hybrid functionals selected. It is found that among
      three popular hybrid density-functional (DF) methods B3LYP, B3PW91, PBE1PBE, and
      a new hybrid-meta-DF method TPSSKCIS, only the PBE1PBE method (with cc-pVTZ basis
      set) gives qualitatively correct energy ordering as that predicted from ab initio
      CCSD(T)/cc-pVDZ [CCSD(T)-coupled-cluster method including singles, doubles, and
      noniterative perturbative triples; cc-pVDZ-correlation consistent polarized
      valence double zeta] as well as from MP4(SDQ)/cc-pVTZ [MP4-fourth-order Moller
      Plesset; cc-pVTZ-correlation consistent polarized valence triple zeta]
      calculations. Both CCSD(T) and MP4 calculations indicate that the bowl is most
      likely the global minimum of neutral C(20) isomers, followed by the fullerene
      cage and ring. For the anionic counterparts, the PBE1PBE calculation also agrees
      with MP4/cc-pVTZ calculation, both predicting that the bowl is still the lowest
      energy structure of C(20)(-) at T=0 K, followed by the ring and the cage. In
      contrast, both B3LYP/cc-pVTZ and B3PW91/cc-pVTZ calculations predict that the
      ring is the lowest-energy structure of C(20)(-). Apparently, this good
      reliability in predicting the energy ordering renders the hybrid PBE method a
      leading choice for predicting relative stability among large-sized carbon
      clusters and other carbon nanostructures (e.g., finite-size carbon nanotubes,
      nano-onions, or nanohorns). The relative stabilities derived from total energy
      with Gibbs free-energy corrections demonstrate a changing ordering in which ring
      becomes more favorable for both C(20) and C(20)(-) at high temperatures. Finally,
      photoelectron spectra (PES) for the anionic C(20)(-) isomers have been computed.
      With binding energies up to 7 eV, the simulated PES show ample spectral features
      to distinguish the three competitive C(20)(-) isomers.

PMID- 15945716
TI  - Momentum-space properties from coordinate-space electron density.
AB  - Electron density and electron momentum density, while independently tractable
      experimentally, bear no direct connection without going through the many-electron
      wave function. However, invoking a variant of the constrained-search formulation
      of density-functional theory, we develop a general scheme (valid for arbitrary
      external potentials) yielding decent momentum-space properties, starting
      exclusively from the coordinate-space electron density. A numerical illustration
      of the scheme is provided for the closed-shell atomic systems He, Be, and Ne in
      their ground state and for 1s(1) 2s(1) singlet electronic excited state for
      helium by calculating the Compton profiles and the <p(n)> expectation values
      derived from given coordinate-space electron densities.

PMID- 15945717
TI  - Relativistic effective valence shell Hamiltonian method: excitation and
      ionization energies of heavy metal atoms.
AB  - The relativistic effective valence shell Hamiltonian H(v) method (through second
      order) is applied to the computation of the low lying excited and ion states of
      closed shell heavy metal atoms/ions. The resulting excitation and ionization
      energies are in favorable agreement with experimental data and with other
      theoretical calculations. The nuclear magnetic hyperfine constants A and
      lifetimes tau of excited states are evaluated and they are also in accord with
      experiment. Some of the calculated quantities have not previously been computed.

PMID- 15945718
TI  - UV photodissociation of the van der Waals dimer (CH3I)2 revisited: pathways
      giving rise to ionic features.
AB  - The CH(3)I A-state-assisted photofragmentation of the (CH(3)I)(2) van der Waals
      dimer at 248 nm and nearby wavelengths has been revisited experimentally using
      the time-of-flight mass spectrometry with supersonic and effusive molecular beams
      and the "velocity map imaging" technique. The processes underlying the appearance
      of two main (CH(3)I)(2) cluster-specific features in the mass spectra, namely,
      I(2)(+) and translationally "hot" I(+) ions, have been studied. Translationally
      hot I(+) ions with an average kinetic energy of 0.94+/-0.02 eV appear in the one
      quantum photodissociation of vibrationally excited I(2)(+)((2)Pi(32,g)) ions
      (E(vib)=0.45+/-0.11 eV) via a "parallel" photodissociation process with an
      anisotropy parameter beta=1.55+/-0.03. Comparison of the images of I(+) arising
      from the photoexcitation of CH(3)I clusters versus those from neutral I(2) shows
      that "concerted" photodissociation of the ionized (CH(3)I)(2)(+) dimer appears to
      be the most likely mechanism for the formation of molecular iodine ion I(2)(+),
      instead of photoionization of neutral molecular iodine.

PMID- 15945719
TI  - Calculation of accurate permanent dipole moments of the lowest 1,3Sigma+ states
      of heteronuclear alkali dimers using extended basis sets.
AB  - Obtaining ultracold samples of dipolar molecules is a current challenge which
      requires an accurate knowledge of their electronic properties to guide the
      ongoing experiments. In this paper, we systematically investigate the ground
      state and the lowest triplet state of mixed alkali dimers (involving Li, Na, K,
      Rb, Cs) using a standard quantum chemistry approach based on pseudopotentials for
      atomic core representation, Gaussian basis sets, and effective terms for core
      polarization effects. We emphasize on the convergence of the results for
      permanent dipole moments regarding the size of the Gaussian basis set, and we
      discuss their predicted accuracy by comparing to other theoretical calculations
      or available experimental values. We also revisit the difficulty to compare
      computed potential curves among published papers, due to the differences in the
      modelization of core-core interaction.

PMID- 15945720
TI  - Pseudorotation motion in tetrahydrofuran: an ab initio study.
AB  - The use of different models based on experimental information about the observed
      level splitings, rotational constants, and far-infrared transition frequencies
      leads to different predictions on the equilibrium geometry for tetrahydrofuran.
      High-level ab initio calculations [coupled cluster singles, doubles
      (triples)/complete basis set (second order Moller-Plesset triple, quadrupole,
      quintuple)+zero-point energy(anharmonic)] suggest that the equilibrium
      conformation of tetrahydrofuran is an envelope C(s) structure. The theoretical
      geometrical parameters might be helpful to plan further microwave spectroscopic
      studies in order to get a physical interpretation of the measurements.

PMID- 15945721
TI  - Anion of the formic acid dimer as a model for intermolecular proton transfer
      induced by a pi* excess electron.
AB  - The neutral and anionic formic acid dimers have been studied at the second-order
      Moller-Plesset and coupled-cluster level of theory with single, double, and
      perturbative triple excitations with augmented, correlation-consistent basis sets
      of double- and triple-zeta quality. Scans of the potential-energy surface for the
      anion were performed at the density-functional level of theory with a hybrid
      B3LYP functional and a high-quality basis set. Our main finding is that the
      formic acid dimer is susceptible to intermolecular proton transfer upon an excess
      electron attachment. The unpaired electron occupies a pi(*) orbital, the
      molecular moiety that accommodates an excess electron "buckles," and a proton is
      transferred to the unit where the excess electron is localized. As a consequence
      of these geometrical transformations, the electron vertical detachment energy
      becomes substantial, 2.35 eV. The anion is barely adiabatically unstable with
      respect to the neutral at 0 K. However, at standard conditions and in terms of
      Gibbs free energy, the anion is more stable than the neutral by +37 meV. The
      neutral and anionic dimers display different IR characteristics. In summary, the
      formic acid dimer can exist in two quasidegenerate states (neutral and anionic),
      which can be viewed as "zero" and "one" in the binary system. These two states
      are switchable and distinguishable.

PMID- 15945722
TI  - Theoretical study on germanium cyanide radical GeCN and its ions.
AB  - A detailed theoretical study is performed on the hitherto unknown germanium
      cyanide radical and its ions. The (2)Pi state GeCN lies 5.0 kcal/mol lower than
      the (2)Pi state GeNC at the coupled-cluster theory including single and double
      excitations and perturbative inclusion of triple excitations [CCSD(T)]/6
      311++G(3df)//quadratic configuration interaction with single and double
      excitations (QCISD)/6-311G(d)+zero-point vibrational energy (ZPVE) level. For
      interconversion between them, two electronic state pathways (2)A(') and (2)A(")
      are located, with the latter being 0.7 kcal/mol more favorable than the former.
      On the (2)A(") path, the GeCN-->GeNC and GeNC-->GeCN conversion barriers are 14.5
      and 9.5 kcal/mol, respectively. The detailed singlet and triplet potential-energy
      surfaces of both the cationic and anionic GeCN species are also investigated. On
      the ground-state electronic hypersurface, singlet GeNC(+) is 4.6 kcal/mol more
      stable than singlet GeCN(+), whereas triplet GeNC(-) is 10.0 kcal/mol less stable
      than triplet GeCN(-). The relative energy difference between the GeCN(0,+/-) and
      GeNC(0,+/-) can be well correlated with the number of vacant orbitals on the Ge
      atom. The stability of the neutral and ionic CGeN and cyclic cGeCN is also
      discussed. The predicted structures, spectroscopies, ionization, and affinity
      energies as well as the Renner-Teller properties are expected to provide reliable
      estimates for future characterization of the potential GeCN and GeNC radicals as
      well as their ionic counterparts both in the laboratory and in the interstellar
      space.

PMID- 15945723
TI  - Calculation of the tau dependence of the vibration-internal rotation-overall
      rotation interactions in CH3OH from molecular structure and molecular dynamics.
AB  - The Guan and Quade theory for vibration-large-amplitude internal-motion-rotation
      interactions has been applied to the internal rotation problem in CH(3)OH.
      Through the molecular dynamics, the cos 3tau and sin 3tau dependence of the
      torsional-rotational coefficients in the effective Hamiltonian have been
      calculated from molecular structure. The internal rotation coordinate tau(') for
      the vibrationally distorted molecule is shown to have the necessary threefold
      symmetry for all values of tau('). For the methyl deformation modes, the
      vibrational dependence of the internal rotation potential energy is shown to have
      a threefold symmetry. The S(t) and S(t)S(t) dependence of the inertia tensor and
      Coriolis coupling coefficients has been developed in terms of curvilinear
      internal coordinates. The T transformation separating rotation from vibrations in
      zeroth order is then applied, the kinetic-energy tensor inverted to momentum
      space, and finally the effective torsion-rotation coefficients are calculated by
      Van Vleck perturbation theory. When compared to the empirical results, the
      kinetic-energy contributions to the cos 3tau and sin 3tau dependence of the
      coefficients are as follows: 54% of P(a)(2) is accounted for, 28% of P(a)P(b),
      16% of P(a)P(c), and 91% of the asymmetry. The calculation is inadequate to
      account for the P(b)(2),P(c)(2), and P(b)P(c) coefficients, ranging from factors
      of 20-70, even with the incorrect sign for some of the terms. Anharmonic force
      contributions from the vibrations have not been used in the calculation since
      these forces are not known at this time.

PMID- 15945724
TI  - Ab initio potential-energy surface for the reaction Ca+HCl-->CaCl+H.
AB  - The potential-energy surface of the ground electronic state of CaHCl has been
      obtained from 6400 ab initio points calculated at the multireference
      configuration-interaction level and represented by a global analytical fit. The
      Ca+HCl-->CaCl+H reaction is endothermic by 5100 cm(-1) with a barrier of 4470 cm(
      1) at bent geometry, taking the zero energy in the Ca+HCl asymptote. On both
      sides of this barrier are potential wells at linear geometries, a shallow one due
      to van der Waals interactions in the entrance channel, and a deep one attributed
      to the H(-)Ca(++)Cl(-) ionic configuration. The accuracy of the van der Waals
      well depth, approximately 200 cm(-1), was checked by means of additional
      calculations at the coupled-cluster singles and doubles with perturbative triples
      level and it was concluded that previous empirical estimates are unrealistic.
      Also, the electric dipole function was calculated, analytically fitted in the
      regions of the two wells, and used to analyze the charge shifts along the
      reaction path. In the insertion well, 16,800 cm(-1) deep, the electric dipole
      function confirmed the ionic structure of the HCaCl complex and served to
      estimate effective atomic charges. Finally, bound rovibrational levels were
      computed both in the van der Waals well and in the insertion well, and the
      infrared-absorption spectrum of the insertion complex was simulated in order to
      facilitate its detection.

PMID- 15945725
TI  - Low temperature pressure broadening of OCS by He.
AB  - We report experimentally measured cross sections for pressure broadening of OCS
      by He from 4.2 to 23 K. These measurements were made in a quasiequilibrium cell
      using the collisional cooling technique. Cross sections were obtained for the
      broadening of the J=2<--1, J=3<--2, and J=4<--3 rotational transitions of OCS.
      Theoretical cross sections were also calculated using a recent He-OCS potential
      surface. While at the higher temperatures, approximately 20 K, there is only
      modest disagreement between experiment and theory, this disagreement increases
      steadily with decreasing temperature, with predicted cross sections rising
      steeply while the experimental data remains constant or decreases slightly.
      Comparisons to similar recent experimental studies are made and reasons for the
      observed discrepancy between experiment and theory are considered.

PMID- 15945726
TI  - Redshift and blueshift of the Ar-H vibrational stretching frequency in complexes
      of FArH and acetylene.
AB  - Two planar hydrogen-bonded complexes of FArH and acetylene were found to be
      stable using second-order Moller-Plesset perturbation theory (MP2) with 6
      311++G(2d,2p) basis sets. The more stable complex involves bonding between the F
      atom of FArH and a H atom of acetylene, while the other isomer is a T-shaped
      complex with the H atom of FArH bonded to the center of the CC bond of acetylene;
      the zero-point energy corrected dissociation energies are 29 and 27 kJ mol(-1),
      respectively. Interestingly, the Ar-H harmonic vibrational stretching frequency
      is blueshifted in the more stable isomer and redshifted in the less stable form.
      The electron density rearrangement of FArH on complexation was investigated and
      used to explain these unusual findings.

PMID- 15945727
TI  - Ab initio multireference configuration-interaction theoretical study on the low
      lying spin states in binuclear transition-metal complex: magnetic exchange of
      [(NH3)5Cr(mu-OH)Cr(NH3)5]5+ and [Cl3FeOFeCl3]2-.
AB  - The magnetic exchange interaction behavior and energy spectrum of low-lying spin
      states are investigated by using ab initio multireference configuration
      interaction method for the representative binuclear transition-metal complexes
      [(NH(3))(5)Cr(mu-OH)Cr(NH(3))(5)](5+) and [Cl(3)FeOFeCl(3)](2-). Our calculations
      for the nonmodeling real title complexes found that under the appropriate basis
      sets and active space, ab initio method at multireference configuration
      interaction level of theory is able to give accurate energy spectrum of low-lying
      spin states within reachable computation demand nowadays and the deviation of
      magnetic exchange interaction to Lande interval rule can be described by the
      biquadratic correction in terms of Heisenberg spin Hamiltonian. As a methodology
      comparison, density-functional theory combined with broken-symmetry approach
      provides an alternative yet efficient approach to produce accurate numerical
      results, but there are dependences on the particular chosen exchange-correlation
      functionals and system dependent. The spin population analyses at complete active
      space self-consistent-field level of the theory provide an instructively
      understanding and prediction for the magnetic interaction mechanism.

PMID- 15945728
TI  - Ionization energy measurements and electronic spectra for ThO.
AB  - The ionization energy (IE) for ThO has been determined using photoionization
      efficiency and mass-analyzed threshold ionization measurements. An IE of
      6.6038(12) eV was obtained, which was appreciably higher than the result from
      previous appearance potential measurements [6.1(1) eV]. The revised IE is 0.3 eV
      greater than that of atomic Th, indicating that neutral ThO is more tightly bound
      than ThO(+). The one-color two-photon resonant ionization spectrum of ThO was
      examined in the range of 315-370 nm. Rotationally resolved bands were recorded
      for three new electronic states (designated as E('),F('), and G(')). In addition,
      transitions to the A(')(v=1,2,3) levels and the N(v=2) level were observed for
      the first time. Ligand field theory predictions [L. A. Kaledin, J. E. McCord, and
      M. C. Heaven, J. Mol. Spectrosc. 164, 27 (1994)] were used to propose
      configurational assignments for 20 electronically excited states.

PMID- 15945729
TI  - Detection of O(3P(J)) atoms formed by reaction, Al+O2--> AlO+O under crossed-beam
      condition.
AB  - The vacuum ultraviolet laser-induced fluorescence technique was employed to
      detect the oxygen atoms formed by the reaction, Al+O(2)--> AlO+O. The
      measurements were carried out under the crossed-beam condition at 12.2 kJmol of
      collision energy. The relative populations of three spin-orbit states of
      O((3)P(J)) were determined to be 3.8, 1.0, and 0.2 for J=2, 1, and 0,
      respectively. They show nonstatistical populations, i.e., more population in
      O((3)P(2)) and less population in O((3)P(0)) than the statistical expectation.
      These populations were almost identical for two Al beam conditions where the
      relative concentrations of two spin-orbit states of Al, (2)P(1/2), and (2)P(3/2),
      are different. These results suggest that the reaction of Al with O(2) proceeds
      via an intermediate complex where the memory of the initial spin-orbit state is
      lost. Deviation from the statistical population of O((3)P(J)) implies the
      occurrence of the interaction among potential surfaces in the exit channel.

PMID- 15945730
TI  - Experimental and theoretical investigations of the reactions NH(X 3Sigma-) +
      D(2S)-->ND(X 3Sigma-) + H(2S) and NH(X 3Sigma-) + D(2S)-->N(4S) + HD(X 1Sigmag+).
AB  - The rate coefficient of the reaction NH(X (3)Sigma(-))+D((2)S)-->(k(1) )products
      (1) is determined in a quasistatic laser-flash photolysis, laser-induced
      fluorescence system at low pressures. The NH(X) radicals are produced by
      quenching of NH(a (1)Delta) (obtained in the photolysis of HN(3)) with Xe and the
      D atoms are generated in a D(2)/He microwave discharge. The NH(X) concentration
      profile is measured in the presence of a large excess of D atoms. The room
      temperature rate coefficient is determined to be k(1)=(3.9+/-1.5) x 10(13) cm(3)
      mol(-1) s(-1). The rate coefficient k(1) is the sum of the two rate coefficients,
      k(1a) and k(1b), which correspond to the reactions NH(X (3)Sigma(-))+D((2)S)-
      >(k(1a) )ND(X (3)Sigma(-))+H((2)S) (1a) and NH(X (3)Sigma(-))+D((2)S)-->(k(1b)
      )N((4)S)+HD(X (1)Sigma(g) (+)) (1b), respectively. The first reaction proceeds
      via the (2)A(") ground state of NH(2) whereas the second one proceeds in the
      (4)A(") state. A global potential energy surface is constructed for the (2)A(")
      state using the internally contracted multireference configuration interaction
      method and the augmented correlation consistent polarized valence quadrupte zeta
      atomic basis. This potential energy surface is used in classical trajectory
      calculations to determine k(1a). Similar trajectory calculations are performed
      for reaction (1b) employing a previously calculated potential for the (4)A(")
      state. The calculated room-temperature rate coefficient is k(1)=4.1 x 10(13)
      cm(3) mol(-1) s(-1) with k(1a)=4.0 x 10(13) cm(3) mol(-1) s(-1) and k(1b)=9.1 x
      10(11) cm(3) mol(-1) s(-1). The theoretically determined k(1) shows a very weak
      positive temperature dependence in the range 250< or =TK< or =1000. Despite the
      deep potential well, the exchange reaction on the (2)A(") ground-state potential
      energy surface is not statistical.

PMID- 15945731
TI  - Ab initio molecular-orbital study of structures and energetics of Si3H3 neutral
      and anion.
AB  - The geometric structures and isomeric stabilities of various stationary points in
      Si(3)H(3) neutral and its anion are investigated at the coupled-cluster singles,
      doubles (triples) [CCSD(T)] level of theory. For geometrical surveys, the basis
      sets used are of the Dunning's correlation consistent basis sets of triple-zeta
      quality for the neutral. To the anions, the Dunning's correlation consistent
      basis sets of double-zeta quality with diffuse functions are applied. For the
      three lower-lying anion isomers, the Dunning's correlation consistent basis sets
      of triple-zeta quality with diffuse functions (aug-cc-pVTZ) are also used. The
      final energies for the optimized stationary points are calculated at the CCSD(T)
      level of theory with the aug-cc-pVTZ basis sets. The basis sets of 6
      311++G(3df,2pd) were also used for the lower-lying anion isomers. The Gaussian-2
      method was performed only for the lower-lying anion isomers to clarify the
      relative stabilities. The global minimum neutral 1 (C(1):(2)A) has an
      unsymmetrical hydrogen-bridged bond; the conformer 2 in C(s) symmetry is a saddle
      point connecting the two equivalent isomers 1. Two lower-lying isomers (3 and 4)
      are also predicted within the energy range of 20 kJmol. In the anion, however,
      the conformer 4 (C(s):(1)A(')) with five formal valence electrons is a global
      minimum. Two more isomers (2 and 3) lie within 20 kJmol as in the neutral; the
      conformer 1 converts to the isomer 2. The quartets for the neutrals and diradical
      triplets for the anions were further studied; lower-lying quartets and triplets,
      competing with the corresponding doublet and singlet, respectively, were not
      found in the present systems. The vertical and adiabatic electron affinities of
      the global minimum neutral 1, producing the second lowest-lying anion isomer 2,
      amount to 2.18 and 2.35 eV, respectively, at the CCSD(T)/aug-cc-pVTZ level of
      theory. The electron addition to the third lowest-lying neutral isomer 4 produces
      the largest vertical electron affinities of 2.48 eV. The D(3h) structure, being
      the global minimum in the corresponding Si(3)H(3) (+) cation
      (trisilacyclopropenyl cation), converts to the isomer 8 (C(s)) or 11 (C(2)) due
      to the Jahn-Teller effect in the Si(3)H(3) neutral.

PMID- 15945732
TI  - Theoretical characterization of structures and energies of benzene-(H2S)n and
      (H2S)n (n=1-4) clusters.
AB  - An ab initio study was performed in clusters up to four H(2)S molecules and
      benzene using calculations at MP26-31+G(*) and MP2/aug-cc-pVDZ levels.
      Differences between both sets of calculations show the importance of using large
      basis sets to describe the intermolecular interactions in this system. The
      obtained binding energies reflect that benzene has not the same behavior in H(2)S
      as in water, pointing to a higher solubility of this molecule in H(2)S than in
      water. The Bz-cluster binding energy was fitted to an asymptotic representation
      with a maximum value of the energy of -8.00 kcal/mol that converges in a cluster
      with 12 H(2)S molecules. The obtained intermolecular distance in the Bz-H(2)S
      dimer is similar to the experimental value; however, the difference is much
      larger for the angles defining the orientation. The influence of benzene produces
      a distortion of the (H(2)S)(n) clusters, so the intermolecular distances change
      with regard to the (H(2)S)(n) isolated clusters. Frequency shifts are larger in
      clusters with benzene than without it. In the smallest clusters the shift
      associated to the stretching of the S-H bonded to benzene is the largest one, but
      for the cluster with three H(2)S molecules this stretching is combined with the
      other S-H stretching of the molecule so the resulting shift is not the largest
      one.

PMID- 15945733
TI  - Adiabatic squeezing of molecular wave packets by laser pulses.
AB  - Strong pulse sequences can be used to control the position and width of the
      molecular wave packet. In this paper we propose a new scheme to maximally
      compress the wave packet in a quasistatic way by freezing it at a peculiar
      adiabatic potential shaped by two laser pulses. The dynamic principles of the
      scheme and the characteristic effect of the different control parameters are
      presented and analyzed. We use two different molecular models, electronic
      potentials modeled by harmonic oscillators, with the same force constants, and
      the Na(2) dimer, to show the typical yield that can be obtained in compressing
      the initial (minimum width) molecular wave function.

PMID- 15945734
TI  - Higher order (A+E) multiply sign in circle e pseudo-Jahn-Teller coupling.
AB  - The pseudo-Jahn-Teller (PJT) coupling of a nondegenerate state A with a twofold
      degenerate state E by a degenerate vibrational mode e is studied for a general
      system with a C(3) main rotational axis. The PJT coupling terms up to sixth order
      are derived by symmetry considerations for this general (A+E) multiply sign in
      circle e case. The obtained expression for the 3 x 3 diabatic potential energy
      matrix is found to be closely related to the expression recently developed for
      the higher order Jahn-Teller case [A. Viel and W. Eisfeld, J. Chem. Phys. 120,
      4603 (2004)]. The dynamical PJT coupling, which can arise for states of
      appropriate symmetry if one of the vibrational modes induces a change of the
      nuclear point group between D(3h), C(3v), C(3h), and C(3), is discussed. The
      effect of the higher order PJT coupling is tested by a two-dimensional model
      study based on the e bending mode of NH(3)(+). The models are analyzed by fitting
      the two-dimensional potential energy surfaces. The significance of the higher
      order terms on the nonadiabatic dynamics is demonstrated by quantum wave packet
      propagations.

PMID- 15945735
TI  - Collision-induced nonadiabatic transitions in the second-tier ion-pair states of
      iodine molecule: experimental and theoretical study of the I2(f0g+) collisions
      with rare gas atoms.
AB  - Nonadiabatic transitions induced by collisions with He, Ar, Kr, and Xe atoms in
      the I(2) molecule excited to the f0(g)(+) second-tier ion-pair state are
      investigated by means of the optical-optical double resonance spectroscopy.
      Fluorescence spectra reveal that the transition to the F0(u)(+) state is a
      dominant nonradiative decay channel for f state in He, Ar, and Kr, whereas the
      reactive quenching is more efficient for collisions with Xe atom. Total rate
      constants and vibrational product state distributions for the f-->F electronic
      energy transfer are determined and analyzed in terms of energy gaps and Franck
      Condon factors for the combining vibronic levels at initial vibrational
      excitations v(f)=8, 10, 14, and 17. Quantum scattering calculations are performed
      for collisions with He and Ar atoms, implementing a combination of the diatomics
      in-molecule and long-range perturbation theories to evaluate diabatic PESs and
      coupling matrix elements. Calculated rate constants and vibrational product state
      distributions agree well with the measured ones, especially in case of Ar.
      Qualitative comparison is made with the previous results for the second-tier
      f0(g)(+)-->F0(u)(+) transition in collisions with I(2)(X) molecule and the first
      tier E0(g)(+)-->D0(u)(+) transition induced by collisions with the rare gas
      atoms.

PMID- 15945736
TI  - Negative ions of ethylene sulfite.
AB  - The formation of negative ions in molecular beams of ethylene sulfite (ES,
      alternately called glycol sulfite or ethylene glycol, C(2)H(4)SO(3)) molecules
      has been studied using both Rydberg electron transfer (RET) and free electron
      attachment methods. RET experiments with jet-cooled ES show an unexpected broad
      profile of anion formation as a function of the effective quantum number (n(*))
      of the excited rubidium atoms, with peaks at n(max)(*) approximately 13.5 and
      16.8. The peak at n(max)(*) approximately 16.8 corresponds to an expected dipole
      bound anion with an electron binding energy of 8.5 meV. It is speculated that the
      peak at n(max)(*) approximately 13.5 derives from the formation of a distorted
      C(2)H(4)SO(3)(-) ion. We suggest that quasifree electron attachment promotes the
      breaking of one ring bond giving a long-lived acyclic anion and term this process
      incomplete dissociative electron attachment. Theoretical calculations of
      plausible ionic structures are presented and discussed. Electron beam studies of
      ES reveal the presence of multiple dissociative attachment channels, with the
      dominant fragment, SO(2)(-), peaking at 1.3 eV and much weaker signals due to
      SO(3)(-), SO(-), and (ES-H)(-) peaking at 1.5, 1.7, and 0.9 eV, respectively. All
      of these products appear to originate from a broad temporary negative ion
      resonance centered at approximately 1.4 eV.

PMID- 15945737
TI  - Isotope effects in the photofragmentation of symmetric molecules: the branching
      ratio of OD/OH in water.
AB  - With HOD initially in its vibrational ground state, we present a new detailed
      interpretation of the OD/OH branching ratio (approximately 3) in the photoinduced
      process D+OH<--HOD-->H+OD, in the first absorption band. Using semiclassical
      arguments, we show that the branching ratio has little to do with the initial
      distribution of configurations, but the initial momentum distribution plays a key
      role in determination of the branching ratio. The formation of D+OH arises from
      initial situations where OD is stretching, and it stretches faster than OH,
      whereas all other motions lead to H+OD. This picture is confirmed by quantum wave
      packet calculations.

PMID- 15945738
TI  - C2H+H2CO: a new route for formaldehyde removal.
AB  - The title unknown reaction is theoretically studied at various levels to probe
      the interaction mechanism between the ethynyl radical (HC triple bond C) and
      formaldehyde (H(2)C double bond O). The most feasible pathway is a barrier-free
      direct H-abstraction process leading to acetylene and formyl radical
      (C(2)H(2)+HCO) via a weakly bound complex, and then the product can take
      secondary dissociation to the final product C(2)H(2)+CO+H. The C-addition channel
      leading to propynal plus H-atom (HCCCHO+H) has the barrier of only 3.6, 2.9, and
      2.1 kcal/mol at the CCSD(T)/6-311+G(3df,2p)MP2//6-311G(d,p)+ZPVE, CCSD(T)/6
      311+G(3df,2p)//QCISD/6-311G(d,p)+ZPVE, and G3//MP2 levels, respectively [CCSD(T)-
      coupled cluster with single, double, and triple excitations; ZPVE--zero-point
      vibrational energy; QCISD--quadratic configuration interaction with single and
      double excitations; G3//MP2-Gaussian-3 based on Moller-Plesset geometry]. The O
      addition also leading to propynal plus H atom needs to overcome a higher barrier
      of 5.3, 8.7, and 3.0 kcalmol at the three corresponding levels. The title no
      barrier reaction presents a new efficient route to remove the pollutant H(2)CO,
      and should be included in the combustion models of hydrocarbons. It may also
      represent the fastest radical-H(2)CO reaction among the available theoretical
      data. Moreover, it could play an important role in the interstellar chemistry
      where the zero- or minute-barrier reactions are generally favored. Discussions
      are also made on the possible formation of the intriguing propynal in space via
      the title reaction on ice surface.

PMID- 15945739
TI  - On geometries of stacked and H-bonded nucleic acid base pairs determined at
      various DFT, MP2, and CCSD(T) levels up to the CCSD(T)/complete basis set limit
      level.
AB  - The geometries and interaction energies of stacked and hydrogen-bonded uracil
      dimers and a stacked adeninecdots, three dots, centeredthymine pair were studied
      by means of high-level quantum chemical calculations. Specifically, standard as
      well as counterpoise-corrected optimizations were performed at second-order
      Moller-Plesset (MP2) and coupled cluster level of theory with single, double, and
      perturbative triple excitations [CCSD(T)] levels with various basis sets up to
      the complete basis set limit. The results can be summarized as follows: (i)
      standard geometry optimization with small basis set (e.g., 6-31G(*)) provides
      fairly reasonable intermolecular separation; (ii) geometry optimization with
      extended basis sets at the MP2 level underestimates the intermolecular distances
      compared to the reference CCSD(T) results, whereas the MP2/cc-pVTZ counterpoise
      corrected optimization agrees well with the reference geometries and, therefore,
      is recommended as a next step for improving MP2/cc-pVTZ geometries; (iii) the
      stabilization energy of stacked nucleic acids base pairs depends considerably on
      the method used for geometry optimization, so the use of reliable geometries,
      such as counterpoise-corrected MP2/cc-pVTZ ones, is recommended; (iv) the density
      functional theory methods fail completely in locating the energy minima for
      stacked structures and when the geometries from MP2 calculations are used, the
      resulting stabilization energies are strongly underestimated; (v) the self
      consistent charges-density functional tight binding method, with inclusion of the
      empirical dispersion energy, accurately reproduces interaction energies and
      geometries of dispersion-bonded (stacked) complexes; this method can thus be
      recommended for prescanning the potential energy surfaces of van der Waals
      complexes.

PMID- 15945740
TI  - Origin of methyl torsional barrier in 1-methyl-2-(1H)-pyridone.
AB  - The laser induced fluorescence excitation and single vibronic excitation
      dispersed fluorescence spectra have been studied for supersonic jet cooled 1
      methyl-2(1h)-pyridone. The methyl torsional bands and some low frequency
      vibrational transitions were assigned for both ground and excited states. The
      torsional parameters V(3)=244 cm(-1) and V(6)=15 cm(-1) for the ground state and
      V(3)=164 cm(-1) and V(6)=40 cm(-1) for the excited state were obtained. To get
      the insight into the methyl torsional barrier, ab initio calculations were
      performed and compared with the experimental results. Origin of potential barrier
      was traced by partitioning the barrier energy into changes in bond-antibond
      interaction, structural, and steric energies accompanying methyl rotation using
      natural bond orbital analysis. The role of local interactions in ascertaining the
      barrier potential reveals that its nature cannot be understood without
      considering the molecular flexing. The hyperconjugation between CHsigma(*) and
      ring pi(*) observed in lowest unoccupied molecular orbital (LUMO) stabilizes the
      methyl group conformer that undergoes a 60 degrees rotation in the excited state
      with respect to that of the ground state, and it is the change in LUMO that plays
      important role in the excited state barrier formation.

PMID- 15945741
TI  - Geometric phase effects in the H+H2 reaction: quantum wave-packet calculations of
      integral and differential cross sections.
AB  - We report quantum wave-packet calculations on the H+H(2) reaction, aimed at
      resolving the controversy over whether geometric phase (GP) effects can be
      observed in this reaction. Two sets of calculations are reported of the state-to
      state reaction probabilities, and integral and differential cross sections (ICSs
      and DCSs). One set includes the GP using the vector potential approach of Mead
      and Truhlar; the other set neglects the phase. We obtain unequivocal agreement
      with recent results of Kendrick [J. Phys. Chem. A 107, 6739 (2003)], predicting
      GP effects in the state-to-state reaction probabilities, which cancel exactly on
      summing the partial waves to yield the ICS. Our results therefore contradict
      those of Kuppermann and Wu [Chem. Phys. Lett. 349 537 (2001)], which predicted
      pronounced GP effects in the cross sections. We also agree with Kendrick in
      predicting that there are no significant GP effects in the full DCS at energies
      below 1.8 eV, and in the partial (0<or=J<or=10) DCS at energies above this.
      However, we find that in the full DCS above 1.8 eV (which was not reported by
      Kendrick), there are GP effects, which may be experimentally measurable.

PMID- 15945742
TI  - Electronic structure, reactivity, and spectroscopy of dihydrides of group-IB
      metals.
AB  - Atomic pseudopotentials and highly correlated wave functions, including spin
      orbit interactions, have been used to evaluate the electronic structure,
      stability, and spectroscopy of triatomic molecule MH(2), with a metal M belonging
      to group IB (Cu, Ag, and Au). CuH(2) and AuH(2) have been recently observed by IR
      spectroscopy in solid hydrogen and bending anharmonic wave numbers have been
      assigned to these two systems. The AgH(2) molecule has not been detected nor
      experimentally characterized, despite several theoretical works arguing on its
      stability. Our results confirm that the MH(2) radicals have a metastable bent
      ground state separated from the dissociation into [M+H(2)] ground state by
      barriers which have been evaluated to 1.43, 0.78, and 0.80 eV, for Cu, Ag, and Au
      compounds, respectively. These barriers are calculated smaller than in previous
      determinations but still large enough to stabilize the MH(2) systems.
      Spectroscopic data are calculated for these radicals.

PMID- 15945743
TI  - Exploring excited-state hydrogen atom transfer along an ammonia wire cluster:
      competitive reaction paths and vibrational mode selectivity.
AB  - The excited-state hydrogen-atom transfer (ESHAT) reaction of the 7
      hydroxyquinoline(NH(3))(3) cluster involves a crossing from the initially excited
      (1)pipi(*) to a (1)pisigma(*) state. The nonadiabatic coupling between these
      states induces homolytic dissociation of the O-H bond and H-atom transfer to the
      closest NH(3) molecule, forming a biradical structure denoted HT1, followed by
      two more Grotthus-type translocation steps along the ammonia wire. We investigate
      this reaction at the configuration interaction singles level, using a basis set
      with diffuse orbitals. Intrinsic reaction coordinate calculations of the enol-
      >HT1 step predict that the H-atom transfer is preceded and followed by extensive
      twisting and bending of the ammonia wire, as well as large O-H...NH(3) hydrogen
      bond contraction and expansion. The calculations also predict an excited-state
      proton transfer path involving synchronous proton motions; however, it lies 20-25
      kcal/mol above the ESHAT path. Higher singlet and triplet potential curves are
      calculated along the ESHAT reaction coordinate: Two singlet-triplet curve
      crossings occur within the HT1 product well and intersystem crossing to these
      T(n) states branches the reaction back to the enol reactant side, decreasing the
      ESHAT yield. In fact, a product yield of approximately 40% 7
      ketoquinoline.(NH(3))(3) is experimentally observed. The vibrational mode
      selectivity of the enol-->HT1 reaction step [C. Manca, C. Tanner, S. Coussan, A.
      Bach, and S. Leutwyler, J. Chem. Phys. 121, 2578 (2004)] is shown to be due to
      the large sensitivity of the diffuse pisigma(*) state to vibrational
      displacements along the intermolecular coordinates.

PMID- 15945744
TI  - Vibronic coupling in the excited cationic states of ethylene: simulation of the
      photoelectron spectrum between 12 and 18 eV.
AB  - The effect of vibronic coupling on structure and spectroscopy is investigated in
      the excited cationic states of ethylene. It is found from equation of motion
      coupled cluster singles and doubles method for ionization potential electronic
      structure calculations in a triple-zeta plus double polarization basis set that
      ethylene in its third (B (2)A(g)) and fourth (C (2)B(2u)) ionized states does not
      have a stable minimum-energy geometry. The potential-energy surfaces of these
      states are energetically distinct and well separated at the ground-state geometry
      of ethylene, but in a geometry optimization as the structure of the ion relaxes,
      these surfaces end up in conical intersections and finally in the stable
      equilibrium geometry of the second ionized state (A (2)B(3g)). The topology of
      the potential-energy surfaces can be clearly understood using a vibronic model
      Hamiltonian. Furthermore, by diagonalizing this model Hamiltonian, the
      photoelectron spectrum of ethylene corresponding to the second, third, and fourth
      ionized states (12-18 eV) is simulated. Spectra from vibronic simulations
      including up to quartic coupling constants and using various normal-mode basis
      sets are compared to those from vertical Franck-Condon simulations to understand
      the importance of vibronic coupling and nonadiabatic effects and to examine the
      influence of individual normal modes on the spectrum.

PMID- 15945745
TI  - Ionization potentials of small lithium clusters (Lin) and hydrogenated lithium
      clusters (LinH).
AB  - We present accurate ionization potentials (IPs) for small lithium clusters and
      hydrogenated lithium clusters (n=1-4), computed using coupled-cluster singles and
      doubles theory augmented with a perturbative correction for connected triple
      excitations [CCSD(T)] with the correlation-consistent weighted core-valence
      quadruple-zeta basis set (cc-pwCVQZ). In some cases the full CCSDT method has
      been used. Comparison of computed binding energies with experiment for the pure
      cationic lithium clusters reveals excellent agreement, demonstrating that
      previous discrepancies between computed and experimentally derived atomization
      energies for the corresponding neutral clusters are due to the use of an
      inaccurate experimental IP for Li(4). The experimental IP for Li(4) falls 0.43 eV
      below our theoretical adiabatic value of 4.74 eV, which should be a lower bound
      to the measured IP. Our recommended zero-point corrected adiabatic IPs for Li,
      Li(2), Li(3), Li(4), LiH, Li(2)H, Li(3)H, and Li(4)H are 5.39, 5.14, 4.11, 4.74,
      7.69, 3.98, 4.69, and 4.05 eV, respectively. Zero-point vibrationally corrected
      CCSD(T) atomization energies per atom for Li(2) (+), Li(3) (+), Li(4) (+),
      LiH(+), Li(2)H(+), Li(3)H(+), and Li(4)H(+) are 0.64, 0.96, 0.90, 0.056, 1.62,
      1.40, and 1.40 eV, respectively.

PMID- 15945746
TI  - Mechanism for singular behavior in vibrational spectra of topologically
      disordered systems: short-range attractions.
AB  - At low-enough fluid densities, we have found some naive singular behavior, like
      the van Hove singularities in the phonon spectra of lattices, appearing in the
      instantaneous normal mode spectra of the Lennard-Jones (LJ) 2n-n fluids, which
      serve as a prototype of topologically disordered systems. The singular behavior
      cannot be predicted by the mean-field theory, but interpreted by the perturbed
      binary modes of some special pairs, called the mutual nearest neighbor pairs, at
      separations corresponding to the extreme binary frequencies, which are solely
      determined by the attractive part of the LJ 2n-n pair potential. By reducing the
      range of attraction in the pair potential under the conditions of the same
      particle diameter and well depth, the tendency for the appearance of the singular
      behavior shifts to higher fluid densities. From this study, we conclude that pair
      potential with a short-range attraction can be a mechanism to produce a
      counterpart of the van Hove singularity in the vibrational spectra of disordered
      systems without a reference lattice.

PMID- 15945747
TI  - Formation of Liesegang patterns in the presence of an electric field.
AB  - The effects of an external electric field on the formation of Liesegang patterns
      are investigated. The patterns are assumed to emerge from a phase separation
      process in the wake of a diffusive reaction front. The dynamics is described by a
      Cahn-Hilliard equation with a moving source term representing the reaction zone,
      and the electric field enters through its effects on the properties of the
      reaction zone. We employ our previous results [I. Bena, F. Coppex, M. Droz, and
      Z. Racz, J. Chem. Phys. 122, 024512 (2005)] on how the electric field changes
      both the motion of the front, as well as the amount of reaction product left
      behind the front, and our main conclusion is that the number of precipitation
      bands becomes finite in a finite electric field. The reason for the finiteness in
      case when the electric field drives the reagents towards the reaction zone is
      that the width of consecutive bands increases so that, beyond a distance l(+),
      the precipitation is continuous (plug is formed). In case of an electric field of
      opposite polarity, the bands emerge in a finite interval l(-), since the reaction
      product decreases with time and the conditions for phase separation cease to
      exist. We give estimates of l(+/-) in terms of measurable quantities and thus
      present an experimentally verifiable prediction of the "Cahn-Hilliard equation
      with a moving source" description of Liesegang phenomena.

PMID- 15945748
TI  - Predicting equilibrium structures in freezing processes.
AB  - We propose genetic algorithms as a new tool that is able to predict all possible
      solid candidate structures into which a simple fluid can freeze. In contrast to
      the conventional approach where the equilibrium structures of the solid phases
      are chosen from a preselected set of candidates, genetic algorithms perform a
      parameter-free, unbiased, and unrestricted search in the entire search space,
      i.e., among all possible candidate structures. We apply the algorithm to
      recalculate the zero-temperature phase diagrams of neutral star polymers and of
      charged microgels over a large density range. The power of genetic algorithms and
      their advantages over conventional approaches is demonstrated by the fact that
      new and unexpected equilibrium structures for the solid phases are discovered.
      Improvements of the algorithm that lead to a more rapid convergence are proposed
      and the role of various parameters of the method is critically assessed.

PMID- 15945749
TI  - Kinetics of fluorescence quenching for electron transfer and for energy transfer:
      molecular dynamics tests for spherical molecules.
AB  - The Smoluchowski approach to description of fluorescence quenching is tested by
      comparing the theory with computer simulations for the case of spherical
      molecules. The distance dependent sink terms describing the electron transfer
      mechanism and the Forster model for the energy transfer are considered. It is
      shown that the agreement between the rate coefficient from the model and from
      simulations depends on the strength of the solute-solvent interactions as well as
      on the speed of reaction itself. Comparing results of simulations for different
      quencher concentrations we estimate the strength of quencher concentration
      dependence effect and the range of times the effect may be significant. In the
      long time limit the increase in quencher concentration decreased the rate
      coefficient.

PMID- 15945750
TI  - Controlled subnanosecond isomerization of HCN to CNH in solution.
AB  - We report a study of control of the HCN-->CNH isomerization in a liquid Ar
      solution. We show, using molecular dynamics simulations, nearly complete
      conversion from HCN to CNH can be achieved in solution on the subnanosecond time
      scale without requiring laser pulse shaping or molecular alignment. The mechanism
      of the isomerization reaction involves multiphoton rovibrational excitation on
      the ground electronic state potential energy surface coupled with rapid
      rovibrational relaxation in solution. The results demonstrate the important role
      of rotation-vibration coupling in multiphoton excitation of small molecules and
      constitute the first realistic computational demonstration of fast, robust, and
      high-yield laser field manipulation of solution-phase molecular processes.

PMID- 15945751
TI  - Anomalous volumetric behavior of water-hexane and water-decane mixtures in the
      vicinity of the critical region as studied by infrared spectroscopy.
AB  - Infrared spectra of binary mixtures of water with hexane and decane were measured
      at temperatures and pressures in the 473-648 K and 70-350 bar ranges,
      respectively. Volumetric concentrations of water and the hydrocarbons in the
      mixtures were obtained from absorption intensities of the fundamental OH
      stretching band of HDO and combination transitions of the hydrocarbons. Using
      both the concentrations, densities of the aqueous mixtures were estimated and
      compared with densities before mixing, which were calculated using literature
      densities of the neat liquids. It is found that anomalously large volume
      expansion on mixing occurs in the vicinity of the critical region of the
      mixtures.

PMID- 15945752
TI  - Time-resolved measurements of the structure of water at constant density.
AB  - Dynamical changes in the structure factor of liquid water, S(Q,t), are measured
      using time-resolved x-ray diffraction techniques with 100 ps resolution. On short
      time scales following femtosecond optical excitation, we observe temperature
      induced changes associated with rearrangements of the hydrogen-bonded structure
      at constant volume, before the system has had time to expand. We invert this data
      to extract transient changes in the pair correlation function associated with
      isochoric heating effects, and interpret these in terms of a decrease in the
      local tetrahedral ordering.

PMID- 15945753
TI  - Solvatochromic behavior of phenol blue in CO2+ethanol and CO2+n-pentane mixtures
      in the critical region and local composition enhancement.
AB  - The UV-Vis spectra of probe phenol blue in CO(2)+ethanol and CO(2)+n-pentane
      binary mixtures were studied at 308.15 K and different pressures. The experiments
      were conducted in both supercritical region and subcritical region of the
      mixtures by changing the compositions of the mixed solvents. On the basis of the
      experimental results the local compositions of the solvents about phenol blue
      were estimated by neglecting the size difference of CO(2) and the cosolvents.
      Then the local composition data were corrected by a method proposed in this work,
      which is mainly based on Lennard-Jones sphere model. It was demonstrated that the
      local mole fraction of the cosolvents is higher than that in the bulk solution at
      all the experimental conditions. In the near critical region of the mixed
      solvents the local composition enhancement, defined as the ratio of cosolvent
      mole fraction about the solute to that in the bulk solution, increased
      significantly as pressure approached the phase boundary from high pressure. The
      local composition enhancement was not considerable as pressure was much higher
      than the critical pressure. In addition, in subcritical region the degree of
      composition enhancement was much smaller and was not sensitive to pressure in the
      entire pressure range as the concentration of the cosolvents in the mixed
      solvents was much higher than the concentration at the critical point of the
      mixtures.

PMID- 15945754
TI  - Temperature dependence of homogeneous nucleation rates for water: near
      equivalence of the empirical fit of Wolk and Strey, and the scaled nucleation
      model.
AB  - It is pointed out that the temperature fitting function of Wolk and Strey [J.
      Phys. Chem. 105, 11683 (2001)], recently shown to convert the Becker-Doring [Ann.
      Phys. (Leipzig) 24, 719 (1935)] nucleation rate into an expression in agreement
      with much of the experimental water nucleation rate data, also converts the
      Becker-Doring rate into a form nearly equivalent with the scaled nucleation rate
      model, J(scaled)=J(oc) exp[-16piOmega(3)(T(c)T-1)(3)3(ln S)(2)]. In the latter
      expression J(oc) is the inverse thermal wavelength cubed/sec, evaluated at T(c).

PMID- 15945755
TI  - Static and dynamical properties of heavy water at ambient conditions from first
      principles molecular dynamics.
AB  - The static and dynamical properties of heavy water have been studied at ambient
      conditions with extensive Car-Parrinello molecular-dynamics simulations in the
      canonical ensemble, with temperatures ranging between 325 and 400 K. Density
      functional theory, paired with a modern exchange-correlation functional (Perdew
      Burke-Ernzerhof), provides an excellent agreement for the structural properties
      and binding energy of the water monomer and dimer. On the other hand, the
      structural and dynamical properties of the bulk liquid show a clear enhancement
      of the local structure compared to experimental results; a distinctive transition
      to liquidlike diffusion occurs in the simulations only at the elevated
      temperature of 400 K. Extensive runs of up to 50 ps are needed to obtain well
      converged thermal averages; the use of ultrasoft or norm-conserving
      pseudopotentials and the larger plane-wave sets associated with the latter choice
      had, as expected, only negligible effects on the final result. Finite-size
      effects in the liquid state are found to be mostly negligible for systems as
      small as 32 molecules per unit cell.

PMID- 15945756
TI  - A computational study of hydration, solution structure, and dynamics in dilute
      carbohydrate solutions.
AB  - We report results from a molecular simulation study of the structure and dynamics
      of water near single carbohydrate molecules (glucose, trehalose, and sucrose) at
      0 and 30 degrees C. The presence of a carbohydrate molecule has a number of
      significant effects on the microscopic water structure and dynamics. All three
      carbohydrates disrupt the tetrahedral arrangement of proximal water molecules and
      restrict their translational and rotational mobility. These destructuring effects
      and slow dynamics are the result of steric constraints imposed by the
      carbohydrate molecule and of the ability of a carbohydrate to form stable H bonds
      with water, respectively. The carbohydrates induce a pronounced decoupling
      between translational and rotational motions of proximal water molecules.

PMID- 15945757
TI  - Computer simulation study of metastable ice VII and amorphous phases obtained by
      its melting.
AB  - Molecular dynamics simulations of metastable ice VII and cubic ice Ic are carried
      out in order to examine (1) the ability of commonly used water interaction
      potentials to reproduce the properties of ices, and (2) the possibility of
      generating low-density amorphous (LDA) structures by heating ice VII, which is
      known to transform to LDA at approximately 135 K at normal pressure [S. Klotz, J.
      M. Besson, G. Hamel, R. J. Nelmes, J. S. Loveday, and W. G. Marshall, Nature
      (London) 398, 681 (1999)]. We test four simple empirical interaction potentials
      of water: TIP4P [W. L. Jorgensen, J. Chandrasekhar, J. D. Madura, R. W. Impey,
      and M. L. Klein, J. Chem. Phys. 79, 926 (1983)], SPC/E [H. J. C. Berendsen, J. R.
      Grigera, and T. P. Straatsma, J. Phys. Chem. B 91, 6269 (1987)], TIP5P [M. W.
      Mahoney and W. L. Jorgensen, J. Chem. Phys. 112, 8910 (2000)], and ST2 [F. H.
      Stillinger and A. Rahman, J. Chem. Phys. 60, 1545 (1974)]. We have found that
      TIP5P ice VII melts at 210 K, TIP4P at 90 K, and SPC/E at 70 K. Only TIP5P water
      after transition has a structure similar to that of LDA. TIP4P and SPC/E have
      almost identical structures, dissimilar to any known water or amorphous phases,
      but upon heating both slowly evolve towards LDA-like structure. ST2 ice VII is
      remarkably stable up to 430 K. TIP4P and SPC/E predict correctly the cubic ice
      collapse into a high-density amorphous ice (HDA) at approximately 1 GPa whereas
      TIP5P remains stable up to approximately 5 GPa. The densities of the simulated
      ice phases differ significantly, depending on the potential used, and are
      generally higher than experimental values. The importance of proper treatment of
      long-range electrostatic interactions is also discussed.

PMID- 15945758
TI  - Projection of two-dimensional diffusion in a narrow channel onto the longitudinal
      dimension.
AB  - Diffusion in a narrow two-dimensional channel of width A(x), depending on the
      longitudinal coordinate x, is the object of our study. We show how the 2+1
      dimensional diffusion equation can be projected onto a 1+1 dimensional one,
      governing corresponding one-dimensional density, in a steady-state approximation.
      Then we demonstrate the method on a nontrivial exactly solvable case for A(x)=x
      and discuss projection of the initial condition.

PMID- 15945759
TI  - Switching in organic devices caused by nanoscale Schottky barrier patches.
AB  - We have identified a possible electronic origin of metal filaments, invoked to
      explain the switching behavior of organic devices. Interfaces of two
      representative organics polyparaphenylene (PPP) and poly(2-methoxy-5-2-ethyl
      hexyloxy-1,4-phenylenevinylene) with Ag are investigated using ballistic emission
      microscopy. Nanometer scale spatial nonuniformity of carrier injection is
      observed in ballistic electron emission microscopy images of both interfaces. The
      measured Schottky barrier (SB) appears to be consistent with metal states tailing
      into the gap of the PPP. We find that the SB values exhibit a distribution, even
      for the diodes with low ideality factors. The implications of this distribution
      on the measured physical properties of the diode are discussed, in light of work
      on devices of similar geometry, published in the literature. We also demonstrate
      that patches of low SB are likely to nucleate current filaments which can cause
      local ionization and are reported to be responsible for the switching behavior
      observed in metal-organic, metal-CuS and Ag-AgSe structures.

PMID- 15945760
TI  - The wetting-dewetting transition of monolayer water on a hydrophobic metal
      surface observed by surface-state resonant second-harmonic generation.
AB  - The isothermal adsorption and desorption of monolayer water on a Ag(110) surface
      in the temperature range of 130-137 K were characterized by monitoring second
      harmonic (SH) generation from the silver surface. The SH intensity resonantly
      enhanced by the silver surface-state transition is highly sensitive to the amount
      of silver surface area covered by water and allows the observation of an abrupt
      change in the adsorption/desorption behavior at 133.5 K. At temperatures below
      133.5 K water wets the Ag surface in a two-dimensional structure with a measured
      desorption energy of 25.0 (+/-3.3) kJ/mol. At temperatures greater than 133.5 K
      water desorbs from three-dimensional clusters with a measured desorption energy
      of 48.3 (+/-2.2) kJ/mol, in agreement with temperature-programmed desorption
      measurements. This wetting-dewetting transition of water adsorbed on the silver
      surface at 133.5 K is supported by classical nucleation theory calculations.

PMID- 15945761
TI  - Water formation reaction on Pt(111): role of the proton transfer.
AB  - The catalytic water formation reaction on Pt(111) was investigated by kinetic
      Monte Carlo simulations, where the interaction energy between reaction species
      and the high mobility of H(2)O molecule was considered. Results obtained clearly
      reproduce the scanning tunneling microscopy images which show that the reaction
      proceeds via traveling the reaction fronts on the O-covered Pt(111) surface by
      creating H(2)O islands backwards. The reaction front is a mixed layer of OH and
      H(2)O with a (square root 3 x square root 3)R30(o) structure. Coverage change
      during the reaction is also reproduced in which the reaction consists of three
      characteristic processes, as observed by the previous experiments. The simulation
      also revealed that the proton transfer from H(2)O to OH plays an important role
      to propagate the water formation.

PMID- 15945762
TI  - Structural analysis of the reconstructed Si(001)-C surface.
AB  - The atomic structure of reconstructed Si(001)c(4 x 4)-C surface has been studied
      by coaxial impact collision ion scattering spectroscopy. When the 100L of
      ethylene (C(2)H(4)) molecules have been exposed on Si(001)-(2 x 1) surface at 700
      degrees C, it is found that C atoms cause the ordering of missing Si dimer
      defects and occupy the fourth layer of Si(001) directly below the bridge site.
      Our results provide the support for the previous model in which a missing dimer
      structure is accompanied by C incorporation into the subsurface.

PMID- 15945763
TI  - Molecular sieve valves driven by adsorbate-adsorbate interactions: hysteresis in
      permeation of microporous membranes.
AB  - A recently derived mesoscopic framework describing activated micropore diffusion
      is employed to explore system criticality in microporous membranes under
      nonequilibrium conditions. Rapid exploration of parameter space, possible with
      this continuum framework, elucidates a novel temperature-induced ignition and
      extinction of the molecular flux under a macroscopic gradient in pressure
      (chemical potential). Deviation from equilibrium like phase behavior (i.e.,
      shifting and narrowing of phase envelopes and double hysteresis) derives from
      asymmetry of the coupled boundaries of the nonequilibrium membrane. We confirm
      this new phase behavior, akin to "opening" and "closing" of a molecular valve,
      via gradient kinetic Monte Carlo simulations of thin one-dimensional and three
      dimensional systems. The heat of adsorption, strength of adsorbate-adsorbate
      intermolecular forces, and chemical potential gradient are all shown to control
      'valve' actuation, suggesting potential implications in chemical sensing and
      novel diffusion control.

PMID- 15945764
TI  - Chemisorption and diffusion of hydrogen on surface and subsurface sites of flat
      and stepped nickel surfaces.
AB  - Plane-wave density functional theory calculations were performed to investigate
      the binding and diffusion of hydrogen on three flat Ni surfaces, Ni(100),
      Ni(110), and Ni(111), and two stepped Ni surfaces, Ni(210) and Ni(531). On each
      surface, the favored adsorption sites were identified by considering the energy
      and stability of various binding sites and zero-point energy corrections were
      computed. Binding energies are compared with experimental and theoretical results
      from the literature. Good agreement with experimental and previous theoretical
      data is found. At surface coverages where adsorbate-adsorbate interactions are
      relatively weak, the binding energy of H is similar on the five Ni surfaces
      studied. Favorable binding energies are observed for stable surface sites, while
      subsurface sites have unfavorable values relative to the gas phase molecular
      hydrogen. Minimum energy paths for hydrogen diffusion on Ni surfaces and into
      subsurface sites were constructed.

PMID- 15945765
TI  - Condensation and relaxation/transformation of dense t-ZrO2 nanoparticles.
AB  - Dense tetragonal (t)-ZrO(2) nanocondensates were synthesized under very rapid
      heating and cooling by pulsed Nd-YAG (YAG--yttrium aluminum garnet) laser
      ablation with oxygen background gas and characterized by electron diffraction.
      The t-ZrO(2) nanoparticles with a residual stress up to about 5 GPa tended to
      form deformation twins/faults upon local electron dosage. By contrast, the t
      ZrO(2) nanoparticles formed at an-order-of-magnitude higher power have a residual
      stress above 6 GPa and tended to transform into a metastable cubic (c) phase
      vulnerable to amorphization. The relaxation/transformation of the self
      constrained t-ZrO(2) nanoparticles can be rationalized by a lowering of internal
      energy under the influence of resolved shear stress and local electron heating.

PMID- 15945766
TI  - Modeling of configurations and third-order nonlinear optical properties of methyl
      silsesquioxanes.
AB  - Configuration optimizations, excited state properties, and the frequency
      dependent third-order nonlinear optical polarizabilities have been investigated
      on a series of methyl-silsesquioxane (MeT) cages [CH(3)SiO(1.5)](n) (n=4, 6, 8,
      and 10) using ab initio quantum mechanical methods coupled with the sum-over
      states methods. The obtained electronic absorption spectra show a redshift as the
      cage size increases, and the absorption spectra are assigned as charge transfers
      from oxygen p type to silicon s type atomic orbitals. The calculated average
      third-order polarizabilities of <gamma> in the three optical physical processes
      (third-harmonic generation, the electric-field-induced second-harmonic
      generation, and degenerate four-wave mixing) have wide nonresonance regions. For
      all the considered species, the values of gamma decrease in the order of
      [MeT](4)>[MeT](8)(C(2v))=[MeT](10)>[MeT](6)>[MeT](8)(O(h)).

PMID- 15945767
TI  - Self-diffusion of molecular hydrogen in clathrasils compared: dodecasil 3C versus
      sodalite.
AB  - The self-diffusion coefficient of molecular hydrogen through the all-silica
      microporous dodecasil 3C structure is calculated by means of molecular-dynamics
      (MD) calculations, allowing for full framework flexibility, in order to assess
      the material's feasibility as a hydrogen storage medium. The hydrogen uptake rate
      into dodecasil 3C is compared to that previously calculated for sodalite and it
      is found that the latter performs significantly better. The reason for this
      variation in performance is found to lie in intrinsic topological differences
      between each framework type. This is explicitly demonstrated by means of a
      simplified version of transition state theory helping to succinctly rationalize
      the MD data.

PMID- 15945768
TI  - Investigating the properties of supported vesicular layers on titanium dioxide by
      quartz crystal microbalance with dissipation measurements.
AB  - Adsorption of phospholipid vesicles on titanium dioxide was studied by a
      combination of quartz crystal microbalance with dissipation (QCM-D) and atomic
      force microscopy techniques. Vesicle size, concentration in solution, and bilayer
      composition were systematically varied. A strong dependence of the QCM-D response
      (magnitude of the frequency and dissipation factor shifts) on the vesicle
      concentration in solution was observed. QCM-D data were compared with a linear
      viscoelastic model based on the Voight element to determine layer thickness,
      density, elastic modulus, and viscosity. Based on the results of this comparison,
      it is proposed that (i) layer thickness and density, as sensed by QCM-D, saturate
      much earlier (in time) than the actual surface coverage of the vesicles (number
      of vesicles per unit area); (ii) changes in surface coverage that occur after the
      density and thickness, as sensed by QCM-D, have saturated, are interpreted by the
      model as changes in the layer's viscoelastic properties. This is caused by the
      replacement of the viscous media (water) between the vesicles by viscoelastic
      media of similar density (vesicles); (iii) viscoelastic properties of layers
      formed at different vesicle concentrations differ significantly, while the
      vesicle surface coverage in those layers does not. Based on the comparison
      between the atomic force microscopy images and QCM-D data acquired at various
      vesicle concentrations it is proposed that QCM-D response is not directly related
      to the surface coverage of the vesicles.

PMID- 15945769
TI  - Kinetic modeling of ion conduction in KcsA potassium channel.
AB  - KcsA constitutes a potassium channel of known structure that shows both high
      conduction rates and selectivity among monovalent cations. A kinetic model for
      ion conduction through this channel that assumes rapid ion transport within the
      filter has recently been presented by Nelson. In a recent, brief communication,
      we used the model to provide preliminary explanations to the experimental current
      voltage J-V and conductance-concentration g-S curves obtained for a series of
      monovalent ions (K(+),Tl(+), and Rb(+)). We did not assume rapid ion transport in
      the calculations, since ion transport within the selectivity filter could be rate
      limiting for ions other than native K(+). This previous work is now significantly
      extended to the following experimental problems. First, the outward rectification
      of the J-V curves in K(+) symmetrical solutions is analyzed using a generalized
      kinetic model. Second, the J-V and g-S curves for NH(4) (+) are obtained and
      compared with those of other ions (the NH(4) (+) J-V curve is qualitatively
      different from those of Rb(+) and Tl(+)). Third, the effects of Na(+) block on
      K(+) and Rb(+) currents through single KcsA channels are studied and the
      different blocking behavior is related to the values of the translocation rate
      constants characteristic of ion transport within the filter. Finally, the
      significantly decreased K(+) conductance caused by mutation of the wild-type
      channel is also explained in terms of this rate constant. In order to keep the
      number of model parameters to a minimum, we do not allow the electrical distance
      (an empirical parameter of kinetic models that controls the exponential voltage
      dependence of the dissociation rate) to vary with the ionic species. Without
      introducing the relatively high number of adjustable parameters of more
      comprehensive site-based models, we show that ion association to the filter is
      rate controlling at low concentrations, but ion dissociation from the filter and
      ion transport within the filter could limit conduction at high concentration.
      Although some experimental data from other authors were included to allow
      qualitative comparison with model calculations, the absolute values of the
      effective rate constants obtained are only tentative. However, the relative
      changes in these constants needed to explain qualitatively the experiments should
      be of significance.

PMID- 15945770
TI  - Intrinsically biased electrocapacitive catalysis.
AB  - We propose the application of the contact potential from metal-metal junctions or
      the built-in potential of semiconductor p-n junctions to induce or catalyze
      chemical reactions. Free of external sources, this intrinsic potential across
      microscale and nanoscale vacuum gaps establishes electric fields in excess of
      10(7) Vm. The electrostatic potential energy of these fields can be converted
      into useful chemical energy. As an example, we focus on the production of
      superthermal gas ions to drive reactions. Analysis indicates that this
      intrinsically biased electrocapacitive catalysis can achieve locally directed ion
      energies up to a few electron volts and local gas temperature boosts in excess of
      10(4) K. Practical considerations for implementation and experimental tests are
      considered.

PMID- 15945771
TI  - Artifacts in dynamical simulations of coarse-grained model lipid bilayers.
AB  - With special focus on dissipative particle dynamics simulations of anisotropic
      and complex soft matter, such as lipid bilayers in water, we have investigated
      the occurrence of artifacts in the results obtained from dynamical simulations of
      coarse-grained particle-based models. The particles are modeled by beads that
      interact via soft repulsive conservative forces (as defined in dissipative
      particle dynamics simulations), harmonic bond potentials, as well as bending
      potentials imparting stiffness to the lipid tails. Two different update schemes
      are investigated: dissipative particle dynamics with a velocity-Verlet-like
      integration scheme [G. Besold, I. Vattulainen, M. Karttunen, and J. M. Polson,
      Phys. Rev. E 63, R7611 (2000)] and Lowe-Andersen thermostatting [C. P. Lowe,
      Europhys. Lett. 47, 145 (1999)] with the standard velocity-Verlet integration
      algorithm. By varying the integration time step, we examine various physical
      quantities, in particular pressure profiles and kinetic bead temperatures, for
      their sensitivity to artifacts caused by the specific combination of integration
      technique and the thermostat. We then propose a simple fingerprint method that
      allows monitoring the presence of simulation artifacts.

PMID- 15945772
TI  - Long-range many-body polyelectrolyte bridging interactions.
AB  - We investigate polyelectrolyte bridging interactions mediated by charged,
      flexible, polyelectrolyte chains between fixed cylindrical macroions of opposite
      charge in a two-dimensional hexagonal crystalline array. We show that in the
      asymptotic regime of small macroion density, the polyelectrolyte-mediated
      attraction is long range, falling off approximately linearly with the macroion
      array density. We investigate the polyelectrolyte free energy as a function of
      the macroion density and derive several analytic limiting laws valid in different
      regimes of the parameter space.

PMID- 15945773
TI  - Polymer-centered theory in comparison with surfactant-centered theory: a lattice
      Monte Carlo study.
AB  - Lattice Monte Carlo simulation is used to study micellization of both pure and
      surfactant-polymer mixture, with an emphasis on cluster size distribution. The
      amphiphile molecule is of the type H(4)T(4) where the H (head) monomers like the
      solvent molecules and the T (tail) monomers are solvophobic. To compare polymer-
      and surfactant-centered theories, copolymers with the structure of (H(4)T(4))(5)
      are used instead of homopolymers. Since above copolymer molecules have the
      structural unit like the structure of surfactant molecules, it is possible to
      study the competition between the binding of surfactant molecules to the
      copolymer and the micellization in a copolymer-free solution. Results show that,
      first, surfactant molecules bind to the copolymer molecules, and not until
      copolymers are saturated do micelles form. Furthermore, it is shown that for the
      model used in this paper, the polymer-centered theory is more appropriate than
      the surfactant-centered theory, and finally the cooperative nature of cluster
      formation on copolymers is also discussed.

PMID- 15945774
TI  - Charge transfer in DNA: hole charge is confined to a single base pair due to
      solvation effects.
AB  - We include solvation effects in tight-binding Hamiltonians for hole states in
      DNA. The corresponding linear-response parameters are derived from accurate
      estimates of solvation energy calculated for several hole charge distributions in
      DNA stacks. Two models are considered: (A) the correction to a diagonal
      Hamiltonian matrix element depends only on the charge localized on the
      corresponding site and (B) in addition to this term, the reaction field due to
      adjacent base pairs is accounted for. We show that both schemes give very similar
      results. The effects of the polar medium on the hole distribution in DNA are
      studied. We conclude that the effects of polar surroundings essentially suppress
      charge delocalization in DNA, and hole states in (GC)(n) sequences are localized
      on individual guanines.

PMID- 15945775
TI  - Simulated annealing study of morphological transitions of diblock copolymers in
      solution.
AB  - The simulated annealing method was applied to study the self-assembling process
      of diblock copolymers in selective solvents for one block. The simulation results
      illustrated that the morphologies of the copolymer aggregates strongly depend on
      the interactions between the core-forming blocks and the solvents and on the
      length of the corona-forming blocks. Multiple morphological transitions were
      observed in one system. The transition sequence (disordered state-spherical
      micelles-short rodlike micelles-long rodlike micelles-onionlike aggregates) was
      observed for copolymers with increasing core-solvent interaction. Similar
      transitions were observed with the decrease of the length of the corona-forming
      blocks. The mechanisms of these transitions are investigated. The simulation
      results are compared with experiments and other simulations.

PMID- 15945776
TI  - Atomistic molecular-dynamics simulations of the size and shape of polyethylene in
      hexane at infinite dilution.
AB  - Parameters characteristic of size and shape of single polyethylene chains
      consisting of 15-60 monomer units dissolved in hexane are calculated by use of
      molecular-dynamics simulations based on a fully atomistic representation of the
      system. Results are compared with corresponding calculations in vacuum as well as
      Monte Carlo simulations of coarse-grained chains. The major concern of the study
      is a careful check of actual limits and possibilities of atomistic simulations of
      global properties of polymers. As expected such simulations are still restricted
      to rather small chain lengths but are already large enough to obey the
      characteristics of polymer coils.

PMID- 15945777
TI  - Mesoscopic simulation of the crossing dynamics at an entanglement point of
      surfactant threadlike micelles.
AB  - The crossing dynamics at an entanglement point of surfactant threadlike micelles
      in an aqueous solution was studied using a mesoscopic simulation method,
      dissipative particle dynamics, with a coarse-grained surfactant model. The
      possibility of a phantom crossing, which is the relaxation mechanism for the
      pronounced viscoelastic behavior of surfactant threadlike micellar solution, was
      investigated. When two threadlike micelles were encountered at an entanglement
      point under the condition close to thermal equilibrium, they fused to form a four
      armed branch point. Then, a phantom crossing reaction occurred occasionally, or
      one micelle was cut down at the branch point. Increasing the repulsive forces
      between hydrophilic parts of the surfactants, fusion occurred less and the
      threadlike micelle was frequently broken down at an entanglement point. In these
      three schemes (a phantom crossing cut down at the branch point, and break down at
      the entanglement point), the breakage occurs at somewhere along the threadlike
      micelle. The breakage is considered as an essential process in the relaxation
      mechanism, and a phantom crossing can be seen as a special case of these
      processes. To explain the experimental evidence that a terminal of threadlike
      micelles is scarcely observed, a mechanism was also proposed where the generated
      terminal merges into the connected micelle part between two entanglement points
      due to the thermal motion.

PMID- 15945778
TI  - Selection of temperature intervals for parallel-tempering simulations.

PMID- 15945781
TI  - Review: Recent progress in the molecular genetic study of the histo-blood group
      ABO system.

PMID- 15945782
TI  - New human monoclonal antibody reagents for detecting C, c, E, e, K1, Jk(a), and
      Jk(b) red cell antigens.
AB  - Using routine methods, human monoclonal Rh, Kell, and Kidd antibody reagents
      compared favorably with licensed human- source polyclonal antibody reagents when
      typing random donor blood specimens. In three different clinical trials, using
      standard methods and both types of reagents, we tested 2,866 samples by tube, 381
      samples by slide, and, using only monoclonal antibodies (MAbs), 1,043 samples by
      microplate. No discrepant typings were found. More than 95 percent of all
      reactions using MAbs were the same as or stronger than those with polyclonal
      antibodies (PAbs). Use of MAbs instead of PAbs for routine typing will result in
      distinctly stronger reactions, shorter testing times, and decreased anti-human
      globulin reagent and equipment needs. Product quality will be more standardized,
      since uniform batches of antibody from immortalized hybrid cell lines can be made
      available in virtually unlimited supply. Cost-effective production should
      decrease or eliminate dependence on hyperimmunized human and animal donors from
      whom variably reactive reagents are currently obtained. This ease of use and more
      rapid results should improve patient care by facilitating availability of
      phenotype-appropriate red blood cells for special needs.

PMID- 15945783
TI  - A comparison of the reactivity of monoclonal and polyclonal Rh reagents with red
      cells after prolonged storage.
AB  - Previous studies with stored red cells collected into EDTA anticoagulant had
      shown that commercial polyclonal anti-C, -c, and -E reagents gave acceptable
      reactions for 60 days, hut polyclonal anti- e reagents reliably detected the e
      antigen only through 14 days. At that time it was noted that a monoclonal anti-e
      reacted 3+ to 4+ with red cells that no longer reacted, or reacted very weakly,
      with the polyclonal anti-e reagents. This observation led to a comparison study
      of the reactivity of monoclonal versus polyclonal R h reagents with stored red
      cells. Monoclonal and polyclonal anti-C, -c, and -E reagents showed comparable
      reaction strengths, and gave acceptable reactions over the entire testing period.
      Polyclonal anti-e reagents, which are known to he of lower titer, again did not
      give reliable reactions with stored cells after 14 days. However, three different
      monoclonal anti-e reagents were able to detect the presence of the e antigen on
      stored cells for many weeks, This study showed that the monoclonal anti-e
      reagents tested are superior to polyclonal anti-e reagents for typing specimens
      that have been stored for more than 14 days.

PMID- 15945784
TI  - Use of monoclonal Jk(a) and Jk(b) reagents in phenotyping red cells with a
      positive direct antiglobulin test.
AB  - Twenty-five red cell samples with a positive anti-IgG direct antiglobulin test
      QAT) were tested with human monoclonal IgM Jka and jkb antibodies. Red cell
      samples were first tested by a 5- minute incubation tube test with the monoclonal
      antibodies (MAbs). The same red cells were then chloroquine diphosphate (CDP)
      treated, and retested. Eleven of the CDP-treated samples were also tested with
      conventional polyclonal antibodies (PAhs) that required a 37 degrees C incubation
      for 30 minutes, followed by an indirect antiglobulin test. The Jka and Jkb MAbs
      consistently gave the same phenotype results both on untreated DAT-positive red
      cells and on the same cells after CDP treatment. Two of the CDP- treated samples
      had diminished antigen expression with the MAbs, a finding that may have been
      caused by the CDP treatment. One untreated sample, which spontaneously
      agglutinated in a low- protein medium, was incorrectly phenotyped with the anti
      Jka MAb, but both MAbs and PAbs gave the same correct results with the CDP
      treated cells. These findings illustrate that the use of Jka and Jkb MAbs in
      phenotyping DAT-positive specimens is practical and beneficial.

PMID- 15945785
TI  - Case reports: Use of a polyethylene glycol additive to enhance eluate
      sensitivity.
AB  - The use of polyethylene glycol additives to enhance the detection of clinically
      significant alloantibodies in serum has been widely described. This report
      outlines several cases in which polyethylene glycol additives were added to
      eluate test systems to enhance the detection of alloantibodies in recently
      transfused patients.

PMID- 15945786
TI  - An improved method for removal of red cell-bound immunoglobulin using chloroquine
      solution.
AB  - In some patients with autoimmune hemolytic anemia or bemolytic disease of the
      newborn, the red cells are so heavily coated with immunoglobulin that phenotyping
      cannot be carried out unless the antibody is removed without destroying the red
      cell antigens. Studies were performed initially to determine the optimum
      conditions for removal of immunoglobulin from red blood cells (RBCs) using
      chloroquine. Group O, R1r RBCs were coated with serial dilutions of anti-D;
      aliquots were incubated in chloroquine diphosphate (CDP) solution (200 g/L, pH
      5.0) at 18 degrees C, 25 degrees C, 30 degrees C, and 37 degrees C, and test- ed
      by the antiglobulin technique at intervals of 30 minutes for up to 2 hours, the
      results being expressed as titration scores. These studies showed that antibody
      removal was much more efficient at 30 degrees C and 37 degrees C than at 18
      degrees C or 25 degrees C. A further series of experiments was then carried out
      to assess the effect of chloroquine on red cell antigenicity. A 5 percent
      suspension of RBCs heterozygous for c, D, and E antigens, and for Kell, Duffy,
      and Kidd antigens, was incubated at 30 degrees C and at 37 degrees C in
      chloroquine solution. Aliquots were removed at 30-minute intervals for up to 2
      hours, tested with serial dilutions of the appropriate antisera, and titration
      scores obtained. The antigens were well preserved after two hours of chloroquine
      treatment at 30 degrees C. However, when treatment was performed at 37 degrees C,
      aitigenicity had markedly deteriorated by 60 minutes, although the antigens were
      still reasonably well preserved (except for Jkb) at 30 minutes. It is therefore
      recommended that treatment with chloroquine solution prior to typing RBCs heavily
      coated with antibody should be carried out for 90 minutes at 30 degrees C or for
      not more than 30 minutes at 37 degrees C.

PMID- 15945788
TI  - Literature reviews. Fatal or near-fatal transfusion reactions.

PMID- 15945789
TI  - Review: Immune hemolytic anemia and/or positive direct antiglobulin tests caused
      by drugs.

PMID- 15945790
TI  - Cefotetan-induced immune hemolytic anemia due to the drug-adsorption mechanism.
AB  - Positive direct antiglobulin tests (DATs) associated with cephalosporin therapy
      have been reported, but rarely were associated with immune hemolytic anemia
      (IHA). In 1989, we described the first case of IHA associated with cefotetan
      (Cefotantrade mark) causing hemolysis by the drug-adsorption mechanism. We now
      report the full details of ow investigation. The patient was a 23-year-old female
      with a 2 1/2 year history of chronic ulcerative colitis. After 4 days of therapy
      with cefotetan (2 g/day), her hematocrit (Hct) decreased from 34.351 to 23.3%.
      The reticulocyte count was 6.9%. The DAT was 2+ (IgG only), and the serum and an
      eluate were nonreactive with a panel of standard reagent red blood cells (RBCs).
      Cefotetan therapy continued and the patient was transfused with two units of
      RBCs. On day 6 of therapy, the patient experienced an anaphylactoid reaction
      attributed to sensitivity to cefotetan. Cefotetan therapy was discontinued, the
      patient was treated with corticosteroids and epinephrine, and she was transfused
      with an additional unit of RBCs. Her Hct rose to 34.1% prior to her discharge on
      day 11. Further investigation revealed that the patient's serum and an eluate
      contained an antibody that reacted with cefotetan- and cephalothin-coated RBCs by
      the indirect antiglobulin test. In a monocyte monolayer assay, monocytes readily
      phagocytized cefotetan- and cephalothin-coated reagent RBCs but not uncoated
      reagent RBCs. The patient's serum did not react by the so-called immune-complex
      mechanism when cefotetan or cephalothin was added to the patient's serum +
      complement + RBCs.

PMID- 15945791
TI  - Development of a flow cytometric test for the detection of D-positive fetal cells
      after fetomaternal hemorrhage and a survey of the prevalence in D-negative women.
AB  - A sensitive test for the presence of D-positive fetal red blood cells (RBCs) in
      the maternal circulation of D-negative women has been developed. It was used to
      investigate the possibility that the occasional failure in preventing
      alloimmunization might be due to the administration of inadequate amounts of
      prophylactic anti-D Rh immune globulin. The standard dose in Australia contains
      125 microg of antibody, and can suppress immunization by an estimated 6 mL of
      packed D-positive RBCs. A fetomaternal hemorrhage (FMH) of this volume is
      detectable in the maternal circulation as approximately 0.25 percent of the total
      RBCs. Our test utilizes a commercially available human monoclonal IgG anti-D that
      has been biotinylated and used with a dye-conjugated streptavidin. Flow cytometry
      is used to quantitate fluorescing D-positive RBCs. To date, 2,288 tests have been
      performed on blood samples from D-negative women attending local antenatal
      clinics or at the time of delivery. Evidence for an FMH has been obtained in six
      cases (0.26%). In one case, the FMH was only 0.1 percent, and in another
      (confirmed by the Kleihauer-Betke method), fetal cells constituted only 0.2
      percent. Additional Rh immune globulin was not given to these patients. In the
      other four cases, the D-positive fetal cells were estimated to be 0.7,0.5,0.5,
      and 0.4 percent, and additional prophylactic Rh immune globulin was administered.
      Although the prevalence of FMH is low, screening D- negative women at risk of
      alloimmunization has proved to be simple, fast, and inexpensive.

PMID- 15945792
TI  - Application of the Inverness Blood Grouping System for semiautomated ABO and D
      testing of patients' samples.
AB  - We evaluated the performance of the Inverness Blood Grouping System (IBG Systems,
      Inc., Laytonsville, MD) for the ABO and D red cell grouping of patients' samples.
      The IBG System is a semiautomated microplate device for blood grouping and
      antibody detection We tested 2,051 samples using the IBG System and by manual
      grouping techniques. In no instance did the IBG System give a final ABO
      interpretation different from the final manual technique. For three samples, the
      JBG System's ABO interpretation was different from the manual interpretation. An
      error in interpretation by the technologist performing the manual testing was
      responsible for the discrepancies. The IBG System identified one sample as D
      positive that was grouped as D-negative by manual testing. The patient's sample
      had been previously grouped manually as a weak D. Au other D results were in
      agreement. The IBG System provided ABO interpretatinns without technologist's
      intervention on 1,765 (86.1%) of the samples. In 153 (7.5%) of the samples, a
      single, equivocal reaction required visual inspection, but no repeat testing was
      necessary. In 133 (6.5%) of the samples, either repeat testing or reliance on
      only the manual results was required for final ABO group interpretation. The IBG
      System is a reliable and efficient alternative to manual techniques for ABO and D
      grouping of patients' samples.

PMID- 15945793
TI  - Glycine-EDTA treatment to prepare Ko red blood cells: preservation of high
      frequency antigens.
AB  - Reactivity of high-incidence antigens after glycine-EDTA treatment of red blood
      cells (RCs) to prepare artificial Ko RBCs was investigated. The treatment had
      little or no effect on Yta, JMH, Yka, Kna, and McCa. Hy antigen-positive-treated
      RBCs reacted less well with anti-Hy when compared to nontreated cells. Glycine
      EDTA treatment to prepare Ko RBCs offers an advantage over AET treatment because
      it preserves some high-frequency antigens that AET treatment does not.
      Immunohematology 1994;10:64-65.

PMID- 15945796
TI  - Wanted: Discussion group on the internet.

PMID- 15945798
TI  - Literature reviews. General (1993-94).

PMID- 15945799
TI  - Review: Blood group antigens as receptors for bacteria and parasites.

PMID- 15945800
TI  - Misidentification of anti-Vel due to inappropriate use of prewarming and
      adsorption techniques.
AB  - Two units of red blood cells (RBCs) were ordered for a 44-year-old Caucasian
      woman with renal failure and cancer. Pretransfnsion testing performed at the
      regional reference laboratory had revealed the presence of an antibody reactive
      with all cells at the indirect antiglobulin test but apparently nonreactive by a
      prewarmed IAT. The patient's RBCs were direct antiglobulin test negative.
      Adsorption of the serum with rabbit erythrocyte stroma or with allogeneic RBCs at
      4 degrees C reduced the reactivity at the IAT. The patient was transfused with
      two units of washed RBCs and died 6 to 8 hours later. Retrospective testing in
      our laboratory detected anti-Vel in both pretransfusion and posttransfusion
      samples. The pretransfnsion serum was hemolytic when tested io LISS or with
      papain-treated RBCs. Weak reactivity (I+) was observed at the IAT. EDTA-treated
      serum (to prevent C'-mediated hemolysis) was strongly reactive (3+s) with Vel+
      RBCs but compatible with 10 examples of Vel- RBCs. Adsorptions with rabbit RBCs
      did not affect reactivity. Pretransfnsion RBCs were nonreactive with three
      examples of anti- Vel at the IAT. The posttranshision serum was grossly hemolyzed
      and anti-Vel was demonstrable, although weaker than in the pre- transfusion
      sample. The antibody was subclassed as IgG1 and IgG3. In this case, the use of a
      prewarming technique precluded detection of hemolysis caused by the antibody
      prior to the IAT. This case stresses the importance of antibody identification
      and the correct use of such techniques as prewarming and adsorptions.

PMID- 15945801
TI  - Successful transfusion in the presence of anti-K4 (anti-Kpb).
AB  - A 71-year-old group A, DC female, with anti-K4(-Kpb), -E, and -S was admitted for
      her second coronary artery surgery. Four units of autologous red blood cells
      (1BCs) were transfused perioperatively, and four units of homologous K:-4, E-, S-
      RBCs were transfused over the next 24 hours. Ten units of fresh frozen plasma and
      28 units of platelets were also transfused. Continued bleeding necessitated
      calling donors from other states in AUStralia and from the International Panel of
      Donors of Rare Type, Bristol, UK, maintained by the World Health Organization.
      Four units of group 0, K:4, E-, S- KHCs were transfused in the next 24 hours
      while the K:-4 blood was in transit. No immediate signs of a transfusion reaction
      were noted. Blood pressure, temperature, bilirubin, and urinary output were
      normal, and an increase in hemoglobin was observed. A positive direct
      antiglobulin test was evident 3 days posttransfusion of the incompatible units
      and was still present 8 days later. Anti-A and anti-K4 were eluted from the
      patient's RBCs. The titer of anti-K4 increased from 8 preoperatively to 2,048 19
      days posttransfusion of K:4 RBCs. Subsequent transfusions were not required, and
      the patient was discharged 3 weeks after the operation without further incident.

PMID- 15945802
TI  - A comparison of the monocyte monolayer assay with 51chromium red cell recovery
      for determining the clinical significance of red cell alloantibodies.

PMID- 15945803
TI  - State association-sponsored program for SBB candidates.
AB  - Concern about the closure of the only Specialist in Blood Banking (SBB) School in
      the State of Michigan prompted the Michigan Association of Blood Banks (MABB) to
      develop and administer a comprehensive series of lectures to meet the needs of
      technologists seeking SBB certification via the experiential route. The program
      consisted of more than 60 1(1/2)-hour lectures covering all aspects of blood
      banking (genetics, coagulation, immunology, blood group serology, blood
      collection and administration, and transfusion medicine) except infectious
      disease testing and management issues. The latter were presented during two free
      standing one-day seminars (for which a fee was charged for those not registered
      for the lecture series). Educational techniques were covered in a self-study
      module. Two lectures were presented one morning each week from March through
      December, with no presentations during July. Lecturers were local volunteer
      experts, and detailed learning objectives were established for each topic. Each
      registrant was charged a nominal fee ($100 for MABB members; $150 for
      nonmembers). There were 32 registrants for the lecture series, with additional
      registrants for the seminars. Total revenue was $5,100, and expenses amounted to
      approximately $2,400, mostly for faculty honoraria and catering for the two
      seminars. The popularity of our program reflects the need for alternatives to
      formal SBB schools.

PMID- 15945804
TI  - A survey of management of blood donations with unexpected red cell antibodies.
AB  - A survey of 19 large blood centers, each with an average annual collection of
      158,889 units, was conducted to identify. current practices of management of red
      cell units that contain unexpected red cell antibodies. The routine antibody
      identification, distribution, and charge for such units varied widely among the
      19 centers. In addition, although use of these units was low, costs were
      considerable. This survey can serve as a basis for other studies to arrive at
      cost-effective ways to manage such units.

PMID- 15945805
TI  - Literature reviews. General (1994).

PMID- 15945810
TI  - The Rh blood group system: additional complexities.

PMID- 15945811
TI  - Autoimmune hemolysis following transfusion: a mimicking autoanti-D in a D-
      patient with alloanti-D.
AB  - An 80-year-old group O, D- (rr) female with anti-C, -D, -E, and -Fya received
      four units of crossmatch-compatible red blood cells (RBCs). The direct
      antiglobulin test (DAT) was negative. Two weeks later, jaundice, dark urine, a
      16% drop in hematocrit (Hct), a 20% reticulocyte count, and absent haptoglobin
      occurred. During the next month, her DAT was positive with anti-IgG and -C3d.
      Acid eluates, which repeatedly showed anti-D specificity, were nonreactive with
      enzyme-treated D- RBCs. Adsorption with D- RBCs reduced reactivity. An eluate
      from the adsorbing D- RBCs was nonreactive with D+ KBCs. These findings suggest
      an autoantibody mimicking alloanti-D. The patient was treated with prednisone and
      was transfused with group O, D- (rr), K-, Fy(a-) RBCs. Four months later, the Hct
      was stable. One year later, the DAT remained positive and the eluate demonstrated
      a panagglutinin.

PMID- 15945812
TI  - Hemolytic transfusion reactions due to anti-e+f detectable only by nonstandard
      serologic techniques.
AB  - A patient was transfused with a total of 14 units of red blood cells (RBCs) over
      33 days (January 14 to February 15) at two hospitals. Febrile transfusion
      reactions were noted on three occasions, and hemoglobinuria was seen twice.
      Alloantibodies were not detected in a sample dated February 14, following a
      transfusion reaction, and this sample was referred to the North London Blond
      Transfusion Centre. Further samples were also obtained from before and after all
      transfusions at both hospitals. The patient's RBCs typed as A, D+, probable Rh
      phenotype (cDE/cDE). The direct antiglobulin test was negative, and serum samples
      following the second transfusion were red/brown in color. Serologic
      investigations were inconclusive on all samples taken until February 13 (after
      the fourth transfusion). At this time, a weak anti-e reacting by manual polybrene
      technique and an anti-e+f reacting by two-stage papain technique were detected.
      The serum also contained potent HLA antibodies. The patient subsequently received
      leukocyte-depleted group A, cDE/cDE RBCs with out any untoward effect. This case
      demonstrates the importance of a complete transfusion history and emphasizes that
      alloantibodies detectable only by nonstandard techniques can be clinically
      significant.

PMID- 15945813
TI  - Case report: IgG1 Rh antibodies causing moderate hemolytic disease of the
      newborn.
AB  - A gravida 3, para 1,32-year-old black female presented at 27 weeks gestation for
      routine prenatal serologic tests. She typed as group A, D positive, category DIII
      mosaic. IgGl anti-D, -hrB, and -E were identified in her serum Ultrasound
      revealed an apparently normal fetus with no evidence of hydrops or ascites.
      Amniocentesis, performed at 30,33, and 35 weeks, showed some evidence of
      hemolysis that did not increase over time. At 36 weeks of gestation, she
      delivered a full-term infant who was group A, D positive, E negative, with a 3+
      direct antiglobulin test. The eluate revealed anti-D and -hrB, Treatment of the
      hemolytic disease of the newborn included phototherapy, intravenous fluids, and
      transfusion of 60 mL of mother's deglycerolized red blood cells.

PMID- 15945814
TI  - An example of anti-LWa in a 10-month-old infant.
AB  - Blood samples from a 10-month-old male infant requiring transfusion were found to
      contain an allomtibody reacting at 37 degrees C in saline, by indirect
      antiglobulin test (IAT), and with a manual polybrene technique. Preliminary
      results suggested anti-D and another weaker reacting antibody, but the patient
      had been previously transfused with only D- blood. His serum reacted more weakly
      by IAT against red cells treated with 0.2M dithiothreitol (DTT), and one D+, LW(a
      ) sample was nonreactive. The patient's red blood cells (RBCs) typed as B, D-,
      LW(a-), K-, Fy(a-). Due to the age and clinical status of the child, 51Cr
      survival studies were not performed. One pediatric unit of D-, K-, Fy(a-) blood
      was transfused uneventfully; the expected increment of hemoglobin was achieved.
      Repeat testing 3 months later showed a weakly positive DAT, the patient's RBCs
      typed as LW(a+), and anti-LWa was detected only by a two-stage papain technique.
      These results suggest that the patient had a transient depression of LWa with a
      concurrent anti-LWa.

PMID- 15945815
TI  - First example of Rh:-32,-46 red cell phenotype.
AB  - The red cells of a white male blood donor typed as Rh:-1, -2, -3,w4,w5,6,-17,w19,
      31,-32,-34, and -46. Although the donor has no history of transfusion, his serum
      contains an alloantibody that is weakly reactive with most red blood cells (RBCs)
      tested. Only Rhnull and D-- RBCs are nonreactive. Reactivity is enhanced with
      ficin- or papain-treated RBCs and is unaffected by AET or DTT treatment of the
      RBCs. Previously described Rh:-46 RBCs have been of deletion types D--, D, and
      Rhnull, or Rh:32. In three multitransfused patients, the Rh46 antigen was
      temporarily suppressed and the phenotype eventually reverted to normal. This is
      the first report of RBCs of the Rh:-32,-46 phenotype that are not of a rare Rh
      deletion or Rhnull type. In addition, the Rh:w5,w19,-31,-34 phenotype is rarely
      found in whites.

PMID- 15945816
TI  - Loss and reappearance of Rho(D) antigen on the red blood cells of an individual
      with acute myelogenous leukemia.
AB  - Complete loss of Rho(D) antigen from red blood cells (RBCs) of individuals with
      hematologic disorders, though not frequent, has been reported. This case reports
      the loss of D antigen on the RBCs of a patient with acute myelogenous leukemia
      and its reappearance when he was in remission. Loss of D antigen expression
      coincided with worsening clinical and cytogenetic disease. At the time of D
      antigen loss, the patient also had cytogenetic abnormalities in the bone marrow
      cells. When he was in remission, the chromosomal abnormalities were no longer
      detectable, and his RBCs regained D antigen expression.

PMID- 15945817
TI  - The incidence of V (Rh10) and Jsa (K6) in the contemporary African American blood
      donor.
AB  - Following an apparent increase in the number of patients with anti- V and/or anti
      Jsa who required V- and/or Js(a-) red cell units, red cells from African American
      blood donors negative for C, E, S, K, Fya, Fyb, and Jkb were typed for V and Jsa
      over a 2-year period. Of the 438 donors riped for V and Jsa, 168 (38.36%) were V+
      and71 (16.44%) were Js(a+). The incidence of V (Rh10) was higher than that
      reported in previous studies, but no change was seen in the incidence of Jsa
      (K6).

PMID- 15945823
TI  - Warm autoimmune hemolytic anemia: a review of clinical and laboratory
      considerations.

PMID- 15945824
TI  - IgA deficiency.

PMID- 15945825
TI  - Production of anti-Fya in black Fy(a-b-) individuals.

PMID- 15945826
TI  - Report of unusual antibody activity in a nine-week-old child.

PMID- 15945827
TI  - Orientation programs designed to increase cooperation and production.

PMID- 15945828
TI  - Hints for blood bankers.

PMID- 15945829
TI  - Critical evaluation of the scientific literature.

PMID- 15945832
TI  - Literature review: blood groups.

PMID- 15945833
TI  - Cold autoimmune hemolytic anemia: a review of clinical and laboratory
      considerations.

PMID- 15945834
TI  - Anti-Gerbich: a case report.

PMID- 15945835
TI  - IgA deficiency.

PMID- 15945837
TI  - Blood services educators' workshop.

PMID- 15945836
TI  - ABO discrepancy: a case report.

PMID- 15945839
TI  - Results of questionnaire.

PMID- 15945838
TI  - Computers in the laboratory.

PMID- 15945841
TI  - Drug-induced immune hemolytic anemia and/or positive direct antiglobulin tests.

PMID- 15945843
TI  - Monoclonal antibodies to the MNSs sialoglycoproteins.

PMID- 15945842
TI  - An alternative to traditional component competency testing.

PMID- 15945844
TI  - IgA deficiency.

PMID- 15945845
TI  - Alternative part-time SBB training program.

PMID- 15945847
TI  - How to develop and produce educational programs.

PMID- 15945846
TI  - Case report of the rare Co(a- b-) phenotype.

PMID- 15945848
TI  - Developing a telelecture.

PMID- 15945850
TI  - Clinical concerns in autoimmune hemolytic anemia.

PMID- 15945851
TI  - Inhibition of anti-a by group a plasma in group 0 recipients.
AB  - The effect of group A plasma products on the levels of anti-A in group O
      individuals was investigated. The study consisted of six group O patients
      undergoing liver transplant surgery. These patients all received a minimum of 12
      units of whole blood or its equivalent within 24 hours from the start of surgery.
      Three patients acted as a control population and were infused with group 0 plasma
      products while the other three patients received group A plasma products. All
      patients received only group 0 red blood cells. The anti-A scores at 24 hours
      were compared and found to be greatly diminished but not totally eliminated in
      those receiving group A plasma products, while the scores in the control group
      showed little change. This observation is thought to be primarily due to
      hemodilution, but neutralization with soluble group A substance probably played a
      minor role. An unexplained rise in the anti-A scores in four of the patients at
      approximately two weeks postoperatively was noted.

PMID- 15945853
TI  - Case report: LISS panagglutination.

PMID- 15945852
TI  - National Headquarters SBB survey results-part I.

PMID- 15945854
TI  - Case report: antibodies produced by a D-deletion individual.

PMID- 15945856
TI  - International Society of Blood Transfusion (ISBT) Working Party on Terminology
      for Red Cell Surface Antigens.

PMID- 15945855
TI  - Case report: an unusual Rh phenotype that resulted in questionable maternity.

PMID- 15945858
TI  - On the recognition of N-deficient red blood cells and the selection of blood for
      transfusion to patients with anti-N.

PMID- 15945859
TI  - Adsorption of saline-reactive anti-D and -E using gluteraldehyde-fixed rabbit
      erythrocytes and rabbit erythrocyte stroma.

PMID- 15945861
TI  - Inactivation of high incidence antigens on red blood cells by dithiothreitol.

PMID- 15945860
TI  - Alloantibody adsorption by gluteraldehyde-treated rabbit red cells and stroma.

PMID- 15945862
TI  - National Headquarters SBB survey results-part II.

PMID- 15945863
TI  - Case report: paraben-associated anti-JKa.

PMID- 15945865
TI  - Caution: interpretation of panel results may be incorrect.

PMID- 15945864
TI  - A case report: anti-Pr as a cause of blond typing discrepancies:.
AB  - Anti-Pr in the blood of an 83-year-old male patient caused discrepant ABO and Rh
      typing results. The antibody had a titer of 32,000 with adult red cells and
      16,000 with cord red cells at room temperature; there was a prozone in teh first
      two tubes of the titration. The patient's hemogloblin level dropped from 12.2
      g/dl to 9.4 g/dl during his eight-day course of hospitalization.

PMID- 15945867
TI  - The immediate and long-term benefits of a broad-based rare donor program.

PMID- 15945868
TI  - A summary of the black donor screening program at community blood center, Dayton,
      Ohio.

PMID- 15945869
TI  - Evaluation of a rapid technique for antibody elution.
AB  - This study evaluated a new rapid acid elution technique using citric acid. This
      technique was compared to the commonly used digitonin acid procedure. Twenty
      patient or donor antibodies with specificities in the Rhesus, Kell, Kidd, or
      Duffy systems were used to coat red cells. Eluates produced from these cells by
      the citric acid procedure were equivalent or greater in volume and potency to
      those produced by a digitonin acid method. The citric acid procedure required
      five to nine minutes to complete, while the digitonin acid procedure required 28
      to 44 minutes. The citric acid technique is a rapid means of producing a potent
      eluate.

PMID- 15945870
TI  - Evaluation of rapid antibody dissociation techniques.
AB  - Two new antibody dissociation techniques, citric acid treatment and chloroquine
      diphosphate (CDP) treatment at 37 C, were evaluated for their usefulness in
      investigating the red cells of patients with a positive direct antiglobulin test
      (DAT). The techniques were compared to the ZZAP and CDP-22 C procedures for (a)
      removal of coating antibody prior to performing warm autoadsorptions, and (b)
      removal of antibody so antigen typings can be performed. Twenty patient or donor
      antibodies were used to sensitize red cells in vitro. Complete removal of
      antibody was obtained by the CDP-37 C treatment in 19 cases (95%), by ZZAP
      treatment in 17 cases (8 5%), by the citric acid method in 10 cases (50%), and by
      the CDP-22 C method in three cases (15%). The CDP-37 C treatment left all red
      cell antigens investigated intact, and the citric acid technique left all but
      Kell system antigens intact. In addition, patient red cells treated by the citric
      acid technique could be used to adsorb warm-reacting autoantibodies from
      autologous serum in 15 to 30 minutes at room temperature. Investigation of a
      positive DAT may be facilitated by using the citric acid and CDP-37 C treatments.

PMID- 15945871
TI  - Case report explaining an apparent but false maternal exclusion.

PMID- 15945874
TI  - A subgroups and paternity testing.

PMID- 15945872
TI  - A warm autoantibody causing a red cell typing discrepancy.

PMID- 15945875
TI  - National Headquarters SBB survey results-part III.

PMID- 15945876
TI  - Current status and new technologies in parentage testing.

PMID- 15945877
TI  - Neutralization of anti-Sda antibodies with N-acetylgalactosamine.

PMID- 15945878
TI  - A review of the results of paternity testing performed at a community blood
      center.

PMID- 15945880
TI  - Preparing proteolytic enzymes for serologic tests.

PMID- 15945881
TI  - The antiglobulin neutralization test: a procedure for evaluating the efficacy of
      washing red cells for antibody elution.
AB  - The antiglobulin neutralization test, a procedure designed to detect neutralizing
      concentrations of IgG, is compared with the sulfosalicylic acid test and the
      indirect antiglobulin test as a means of evaluating efficacy of protein removal
      by washing red cells prior to antibody elution. Variables that may affect the
      results of the antiglobulin neutralization test and the sulfosalicylic acid test
      are discussed.

PMID- 15945882
TI  - Autoimmune hemolytic anemia due to monoclonal IgM lambda anti-Tja (Anti-P+1+Pk).
AB  - A patient with autoimmune hemolytic anemia of the cold antibody type is
      described. The monoclonal autoantibody had mu heavy and lambda light chains and
      Tja blood group specificity. The antibody resulted in acute hemolysis responsive
      to steroid treatment and appeared simultaneously with an increase in CMV titer.

PMID- 15945883
TI  - Case report: a patient with anti-'N'.

PMID- 15945884
TI  - Serologic characteristics of antibodies recognizing the 'N' antigen.

PMID- 15945885
TI  - Some new Rh antigens: Rh43 to Rh47.

PMID- 15945886
TI  - Stimulation of antibody following 51chromium survival studies.
AB  - The survival of red blood cells (RBCs) radiolabeled with 51Chromium (51Cr) is a
      reliable method for predicting transfusion compatibility. Approximately 1.0 ml of
      51Cr tagged RBCs is infused into the patient and samples are drawn at
      predetermined intervals post infusion to determine RBC survival. Red cells used
      for the study are usually incompatible with the patient's antibody. This
      antigenic rechallenge may stimulate further antibody production, which could
      contribute to accelerated destruction of RBCs during subsequent incompatible
      transfusions. To study this question, blood samples were collected from six
      patients with a single atypical alloantibody, seven to nine months after 51Cr RBC
      survival studies had been performed in an unrelated protocol. Blood had not been
      transfused in the interim. The samples were tested in parallel with pre-survival
      samples for change in antibody titer and score. In addition, RBCs used for the
      51Cr survival study, sensitized in vitro with pre- and post-survival serum, were
      tested by the monocyte monolayer assay (MMA). Serum antibody titers showed a
      significant increase (> 2 dilutions) in two of six patients and antibody score
      was significantly increased (> 10) in three of six patients. One of the two
      negative MMAs became weakly positive. This study suggests that 51Cr survival
      tests using small volumes of RBCs can stimulate significant increases in antibody
      in some patients, a factor that must be considered in performing these tests and
      in planning subsequent transfusions.

PMID- 15945887
TI  - An example of mild hemolytic disease of the newborn caused by anti-Cob.
AB  - A woman whose serum contained multiple alloantibodies delivered a full-term
      infant with mild hemolytic disease of the newborn. The direct antiglobulin test
      performed on the cord cells was positive with monospecific anti-IgG. An acid
      elution performed on the cord cells yielded anti-Cob. These findings were
      consistent with the presence of anti-Cob in the maternal serum. Neonatal clinical
      findings showed a mildly affected infant who demonstrated a moderate rise in
      total bilirubin and slight jaundice. The infant experienced no further
      complications and was discharged.

PMID- 15945891
TI  - Pre-transfusion testing for the chronically transfused, sensitized patient: a
      simple, time-saving approach.

PMID- 15945893
TI  - Auto-anti-AI in the serum of a patient with fatal autoimmune hemolytic anemia.

PMID- 15945892
TI  - Cold autoimmune hemolytic anemia with auto-anti-AI specificity: 51chromium
      survival studies.
AB  - A 65-year-old woman was found to have severe autoimmune hemolytic anemia. The
      patient was group A1, Rho(D) positive. The direct antiglobulin test was strongly
      positive with anti-C3 and negative with anti- IgG. The serum contained two
      distinct IgM antibodies, auto-anti-I and auto-anti-AI. Both were reactive at 22
      degrees C. However, the anti-AI also was reactive in saline and in albumin at 37
      degrees C. An eluate revealed anti-AI and a weak anti-I. Sequential 51Chromium
      survival studies were done with group OI and AI red cells. The group OI red cells
      survived normally (97% at 24 hours) while the group A1I red cells were removed in
      a "two-component" pattern characteristic of IgM complement-fixing antibodies (62%
      survival at one hour, 49% at 24 hours). Based on these observations, the patient
      was subsequently transfused without incidence with six group O units of washed
      red cells prior to splenectomy. Although auto-anti-AI has been previously
      reported, this is the first case to demonstrate the use of 51Cr survival studies
      to determine its clinical significance.

PMID- 15945894
TI  - Early spontaneous abortions in pp women from Northern Sweden.

PMID- 15945895
TI  - Preparation of a simulated warm autoimmune hemolytic anemia specimen for
      instructional purposes in blood banking.

PMID- 15945896
TI  - Anti-'N' nonsense.

PMID- 15945898
TI  - Literature review: membrane chemistry.

PMID- 15945899
TI  - The deleterious effects of dithiothreitol (DTT) on red blood cell LW antigens.

PMID- 15945900
TI  - Unreliability of five elution techniques in an attempt to elute autoanti-LW and
      alloanti-LW.

PMID- 15945901
TI  - A reagent for the conversion of citrated or EDTA plasma to serum.

PMID- 15945902
TI  - A case report: anti:DW and anti-Rh32.

PMID- 15945903
TI  - A case study: an ABO discrepancy due to an antibody to EDTA.

PMID- 15945904
TI  - Hooray for John Judd!

PMID- 15945905
TI  - Microfiltration for capillary tube use.

PMID- 15945906
TI  - Literature review: red blood cell chemistry(part 1).

PMID- 15945908
TI  - Ohio Association of Blood Banks proficiency sample: results for a Du sample.

PMID- 15945907
TI  - Do you do Du?

PMID- 15945909
TI  - The immunohematology consultation report: what, when, how much?

PMID- 15945910
TI  - A case report: paternity case with three alleged fathers and a set of triplets.

PMID- 15945911
TI  - A case report: identification of multiple alloantibodies in a patient's serum.

PMID- 15945912
TI  - Battery operated centrifuge.

PMID- 15945914
TI  - "Do you do Du?".

PMID- 15945913
TI  - Literature review: red blood cell membrane chemistry (part 2).

PMID- 15945915
TI  - Generating visual aids using a microcomputer.

PMID- 15945916
TI  - Immunoglobulin A (IgA) levels in blood products and plasma derivatives.
AB  - Both anaphylactic and anaphylactoid reactions to transfused blood products and
      plasma derivatives have occurred in IgA-deficient patients with antibodies to
      IgA. This study reports the concentration of IgA in various blood products to
      assist in the development of treatment protocols for IgA-deficient patients. Five
      types of blood products and seven types of plasma derivatives were tested for the
      presence of IgA using a semiquantitative hemagglutination inhibition method. The
      concentration of lgA was measured by radial immunodiffusion and enzyme-linked
      immunosorbent assay techniques. Blood products which consistently contained IgA
      less than 0.05 mg/dL(the present definition for IgA deficiency used by the
      American Red Cross Rare Donor Registry) were from IgA-deficient donors,
      deglycerolized red blood cells (RBCs) prepared with an extra wash cycle, and RBCs
      washed using a total volume of approximately 1300 mL of 0.9 percent sodium
      chloride.

PMID- 15945917
TI  - Identification of antibodies on microplates.

PMID- 15945919
TI  - Last-minute slides without a camera.

PMID- 15945918
TI  - Inactivation of Holley (Hy) and Gregory (Gy) antigens by dithiothreitol (DTT).

PMID- 15945921
TI  - The DOS message: "abort, retry, ignore?".

PMID- 15945923
TI  - More on blood group terminology.

PMID- 15945922
TI  - More on Du.

PMID- 15945924
TI  - Serological and immunochemical characteristics of Ge-negative red cells and anti
      Ge.
AB  - Gerbich-negative red cells lack Beta and gamma sialoglycoproteins (SGPs), which
      are now known to carry the Gerbich (Ge) antigens. Gerbich and Yus-type Ge
      negative red cells possess distinct diffuse SGPs that migrate on sodium dodecyl
      sulphate polyacrylamide gel electrophoresis in a position between those normally
      occupied by Beta and gamma SGPs. Both these SGPs lack tie2 antigens and possess
      epitopes recognized by monoclonal anti-Beta These SGPs differ from each other in
      at least two ways. The SGP associated with the Gerbich type also lacks the Ge3
      antigen and is resistant to trypsin treatment. The SGP associated with the Yus
      type possesses the antigenic determinant recognized by anti-Ge3 and is sensitive
      to trypsin digestion.

PMID- 15945925
TI  - A review: occupational safety in blood banking- concepts and conundrums.

PMID- 15945926
TI  - Evaluating the need for Rh immune globulin in some unusual situations.

PMID- 15945927
TI  - Use of a personal computer to determine the statistical validity of antibody
      identification by Fisher's exact method.

PMID- 15945928
TI  - A case report: use of ZZAP reagents in the investigation of warm autoimmune
      hemolytic anemias.

PMID- 15945930
TI  - Hooray for Peter Issitt.

PMID- 15945929
TI  - Plastic sprayer: a device for washing microplates.

PMID- 15945931
TI  - "Do you do Du?".

PMID- 15945932
TI  - Lectins: a hundred years.

PMID- 15945933
TI  - A review: applications of flow cytometry in immunohematology.

PMID- 15945934
TI  - Micropool procedure for routine donor antibody detection.
AB  - Microplate technology was combined with manual sample pooling techniques to
      determine if advantages associated with each method could he realized in a single
      test system. Fresh serum and plasma samples collected from routine blood donors
      and patient samples selected from frozen storage were screened for significant,
      unexpected antibodies. A total of 94 samples with known antibody specificities
      were selected for testing. Two micropool techniques, stream-micropool and mix
      micropool, were compared to a Pooled-tube method. The stream-micropool method
      proved superior in overall detection of the antibodies (85%) and in detection of
      the macroscopically reactive antibodies (96%). Special formulas were used to
      calculate sensitivity, specificity and efficiency of each micropool method. The
      sensitivity of the stream-micropool method was 96 percent and that of the mix
      micropool, 87 percent. For both methods, specificity and efficiency were >/=99
      percent. In a separate study, there was no difference between the use of serum as
      opposed to plasma. Micropool methods offer a sensitive, easily mastered
      alternative to manual tube testing techniques for large hatch donor antibody
      detection.

PMID- 15945935
TI  - Evaluation of a complement-dependent anti-Jka by various sensitization and
      detection methodologies: a case report.
AB  - A 79-year-old woman with a diagnosis of lower gastrointestinal bleeding was found
      to have a complement-dependent anti-Jka in her serum. The anti-Jka was evaluated
      by the antiglobulin technique with polyspecific, anti-C3, and anti-IgG antihuman
      globulin (AHG). A variety of Sensitization and detection methods were used,
      including the prewarmed saline technique, enzyme treatment of test cells, a low
      ionic additive solution (LISS), 22 percent albumin, Polybrene, and an increased
      serum/cell ratio. The anti-Jka was detected only when polyspecific AHG and anti
      C3 were used compared to anti-IgG, regardless of the selected enhancement
      technique. Anti-C3 gave weaker reactions than polyspecific AHG. IgG subclassing
      was inconclusive. The anti-Jka was not detected when plasma was substituted for
      serum. The use of polyspecific versus IgG AHG in pretransfusion testing is
      discussed.

PMID- 15945936
TI  - Educational and scientific posters.

PMID- 15945937
TI  - Literature reviews: computers, red cell membrane chemistry.

PMID- 15945940
TI  - Evaluation of monoclonal anti-A reagents by salivary inhibition studies.
AB  - Ten commercially available monoclonal and polyclonal anti-A reagents were
      evaluated for use in the test for ABH secretor status after finding unexpected
      inhibition with a monoclonal anti-A (reagent Z). Two of the available monoclonal
      reagents were from different batches from the same clone as reagent Z. Those two
      reagents, as well as reagent Z, appeared to be partially neutralized by salivary
      substances from group A nonsecretor individuals. This finding suggests that when
      a saliva inhibition test is done, a nonsecretor control saliva of the same ABO
      group as the saliva to he tested should be used.

PMID- 15945939
TI  - Assessing the clinical significance of anti-Cra and anti-M in a chronically
      transfused sickle cell patient.
AB  - An alloantibody to a high-incidence antigen, associated with multiple other
      alloantibodies, made it impossible to supply antigen-negative red blood cells
      (RBCs) for a chronically transfused sickle cell anemia patient. Anti-Cra,-E,K,-S,
      -Fya, -Fyb, as well as anti-M reactive at 37 degrees C and in the antiglobulin
      phase of testing, were identified in the patient's serum. An extensive search of
      rare donor files at the American Red Cross and at the American ASsociation of
      Blood Banks (AABB) failed to identify Cr(a-),M-,E-,K-,S-, Fy(a-b-) donors.
      Various studies were performed to predict the clinical significance of the anti
      Cra and anti-M. Results of 51chromium survival studies showed 91.8 percent
      survival at 10 minutes and 87.2 percent survival at 60 minutes with Cr(a +),M-, K
      ,S-,Fy(a-b-) donors. Various studies were performed to predict the clinical
      significance of the anti-Cra and anti-M. Results of 51chromium survival studies
      showed 91.8 percent survival at 10 minutes and 87.2 percent survival at 60
      minutes with Cr(a +),M-,E -,K-,S-,Fy(a-b-) red cells, suggesting that immediate
      destruction of transfused CrCa+) red cells would he unlikely. However, further
      analysis revealed diminished long-term survival of the donor's red cells with
      only 60.1 percent recovery at six days (T 1/2 = 12 days) and 10.8 percent at 14
      days (T 1/2 = 4.5 days). A monocyte- monolayer assay (MMA) indicated that both
      the anti-Cra (5.9%) and anti-M (18%) would probably be clinically significant
      (normal value 0-3%). Mass screening continues at several blood centers for Cr(a
      ),M-, E-,K-,S-,Fy(a-b-) donors. However, if no suitable donors are found, the
      results of the 51chromium survival studies and the MMA support the decision to
      transfuse this patient with Cr(a+),M-,F(a- b-),S-,K- ,E- red cells, if necessary.

PMID- 15945941
TI  - Problem solving: a course for blood bankers.
AB  - A structured program for the training of blood bank personnel and students
      entitled "Problem Solving" is presented in its entirety. The explanation includes
      the primary objective for this program, course description, how to evaluate
      student results, a grading system used for errors, and preparation of specimens
      and practical examinations. An example of an actual problem is also presented.

PMID- 15945942
TI  - Database management systems for blood bank applications.
AB  - Blood banks have a need for efficient, long-term storage of records and quick
      access to the stored information. Database management systems make it easy to
      retrieve and review large amounts of data. They provide such functions as data
      entry, sorting capability, search and find capacity, report production,
      calculation and graphic capacities, programming, and the relating of fields in
      one file to those in another file. Privately developed programs can be shared by
      blood banks. A program for managing an inventory of frozen blood units is offered
      in this paper.

PMID- 15945943
TI  - A case report: cold hemagglutinin disease in a pancreatic and renal transplant
      patient.
AB  - A 33-year-old white male, 30 days postpancreatic transplant, with a history of
      juvenile onset diabetes mellitus and previous renal transplant, appeared to have
      cold hemagglutinin disease (CHD). He was being treated for acute organ rejection
      and had received two units of red blood cells (RBCs) on postoperative day 11, at
      which time no serum antibodies were detectable. On postoperative day 30, serum
      studies showed an autoanti-I with a titer of 512 in 30 percent albumin at 4
      degrees C and a maximum thermal amplitude of 37 degrees C. The patient had a
      weakly positive direct antiglobulin test (DAT) with only complement detectable on
      the red cells. The patient recovered spontaneously. The etiology of the CHD is
      unclear. The use of cyclosporin-A, OKT3 monoclonal antibody,and anti-thymocyte
      globulin (ATG) to treat acute rejection could have played a part.

PMID- 15945945
TI  - Long list of priorities.

PMID- 15945946
TI  - Rare blood for a rare patient.

PMID- 15945947
TI  - "Tech hints".

PMID- 15945948
TI  - Literature reviews: computers, autologous transfusion.

PMID- 15945949
TI  - An update on Rodgers and Chido, the antigenic determinants of human C4.
AB  - Rodgers (Rg) and Chido (Ch) blood groups are antigenic determinants of the fourth
      component of human complement (C4). Nine determinants have been defined by means
      of hemagglutination-inhibition (HAI) with polyspecific human antiserums. The
      association of C4A isotypes with Rg and of C4B isotypes with Ch is strong hut not
      complete. Derived amino acid sequences from the C4d region of selected C4
      allotypes of known antigenic expression have provided support for the previously
      reported complex serologic interrelationships. A structural model for antigenic
      determinants at four polymorphic sites, incorporating sequential and
      conformational epitopes, was subsequently proposed. Allotype and Rg/Ch data
      obtained from donors and patients, many with accompanying families, have
      augmented the model and revealed no exceptions. The antigenic determinants,
      therefore, make an important contribution to the complex polymorphism of C4.

PMID- 15945950
TI  - A review: low-frequency red cell antigens.

PMID- 15945951
TI  - QuickBASIC (version 4.5): a user-friendly computer programming tool.

PMID- 15945952
TI  - Analysis of the stability of alanine aminotransferase (ALT) levels in donor
      samples.
AB  - This study was designed to 1) analyze the stability of serum alanine
      aminotransferase (ALT) activity in nonsepanted donor samples stored at room
      temperature (RT) over 72 hours and 2) compare ALT levels of paired samples stored
      at RT and 4 degrees C over the same time period. The study showed that mean ALT
      activities for samples stored at RT increased at all assay times and that those
      stored at 4 degrees C decreased (0.54 IU/L over 72 hours). Although the mean
      increase in activity of the RT samples over 12 hours (1.45 IU/L) was
      statistically significant, it was of little practical significance. For example,
      based on the frequency distribution of the 311 RT samples from this study, and
      using a cut-off value of 69 IU/L, only one unit of blood would have been
      eliminated based on the difference between time zero and 12 hours. It was
      concluded that RT would be the storage of choice for 72 hours, since the tendency
      of ALT levels to decrease during storage at 4 degrees C could make possible the
      inclusion of borderline donor units in the blood supply.

PMID- 15945955
TI  - DNA probe technology in parentage testing.
AB  - Paternity tests involve laboratory procedures on blood samples obtained from the
      alleged father, mother, and child to determine if the alleged father is the true
      father. Conclusions are based on the principle that the child inherits half of
      the characteristics (markers) in his/her blood from each true parent. DNA probe
      analysis has emerged from the research laboratory and is currently being utilized
      by laboratories engaged in parentage testing to improve their efficiency in
      discriminating between fathers and nonfathers. This new technique provides a very
      powerful tool.

PMID- 15945957
TI  - A review: the Duffy blood group system.

PMID- 15945956
TI  - Investigation of transfusion reactions through microcomputer education software.
AB  - The purpose of this study was to develop educational software to simulate
      laboratory investigation of transfusion reactions. An interactive, branching
      style program was developed using a 256K Personal Computer (International
      Business Machines, Boca Raton, FL). Over 75 institutions in the United States and
      Canada are currently using the software in preprofessional and continuing
      professional education programs.

PMID- 15945958
TI  - A case report: unusual Gerbich antibody in a patient with sickle cell anemia.
AB  - A patient whose red blood cells (RBCs) typed as Ge:2,3 produced an alloantibody
      to a high-frequency antigen in the Gerbich system. This antibody was shown to be
      nonreactive with Ge:-2,-3 KBCs using adsorption-elution studies. A monocyte
      monolayer assay (MMA) suggested that transfusion of Ge:2,3 KBCs to this patient
      would have reduced in vivo survival.

PMID- 15945959
TI  - Resolution of discrepant typings observed in paternity testing.
AB  - Discrepant results in phenotyping the red blood cells (RBCs) of a child and his
      alleged parents were attributable to a contaminating antibody, anti-Bgb (HLA B
      17), in typing reagents (anti-C and -Cw). This case demonstrates the necessity
      for using reagents from at least two sources for paternity testing.

PMID- 15945961
TI  - Clinical significance of anti-Cra and -M.

PMID- 15945963
TI  - A review: the enzyme-linked antiglobulin test (ELAT) and its applications for
      reference laboratories.

PMID- 15945962
TI  - Auberger red cell antigens are not part of the Kell, Colton, or Dornbrock blood
      group systems.
AB  - Since 1981, red cell samples from families were tested with anti-Aua and, since
      1986, with both anti-Aua and anti-Aub in an attempt to elevate Auberger to a
      blood group system status. The results show that Auberger is not pan of the Kell
      (five families), Colton (three Families), or Dombrock (two families) blood group
      systems. Exclusion from four more systems (Di, Yt, LW, Ch:Rg) is required before
      system status may be claimed.

PMID- 15945964
TI  - The elucidation of a Kell-related autoantibody using ZZAP-treated red cells.
AB  - A 61-year-old, nontransfused, Caucasian male was found to have a positive direct
      antiglobulin test (DAT) and an autoantibody in his serum prior to total hip
      replacement. Autoabsorption with the patient's ZZAP-treated red cells failed to
      absorb the autoantibody, giving a clue to its possible specificity, which was
      subsequently found to be Kell-system related. In addition, his red cells were
      found to have a slightly weakened expression of Kell system antigens. The patient
      was fit and healthy with normal hematological indices at the time of the
      operation. One year the hemlogical findings remained the same despite the
      persistence of the autoantibody and a positive DAT. This suggested that the
      autoantibody was benign, which was supported by a negative in vitro mactophage
      assay.

PMID- 15945965
TI  - A simple alternative for Rh phenotyping red cells that have a persistently
      positive Rh control.
AB  - Investigation of a patient's red cell sample with a persistently positive Rh
      control revealed that if the patient's red cells were treated with ZZAP, then
      incubated at 37 degrees C with commercial Rhtyping reagents, then washed four
      times with saline, the positive Rh control could be circumvented and the Rh
      phenotype readily determined. One hundred red cell samples of known Rh phenotype
      were treated with ZZAP and coated with autoantibody to resemble the cells of the
      index case. Accurate results were obtained when these modified cell samples were
      tested against Rh typing reagents from three manufacturers using a 37 degrees C
      incubation followed by four saline washes. The procedure, termed Z37W, appears to
      be a simple alternative that can assist in determination of Rh phenotypes when
      the Rh control is positive.

PMID- 15945969
TI  - Current viewpoints on mechanisms causing drug-induced immune hemolytic anemia
      and/or positive direct antiglobulin tests.

PMID- 15945966
TI  - Mastering the PC floppy disk maze.

PMID- 15945970
TI  - Recovery of costs for special procedures done in reference laboratories.
AB  - In recent years, blood bank laboratories have been encouraged to look at special
      procedures that might generate needed revenues. Laboratories that elect to offer
      special procedures to recover costs or to generate revenue should evaluate each
      test carefully Areas to be considered are the projected demand for the test,
      proficiency of present laboratory staff, cost of reagents and equipment, and
      assay time relative to labor cost.

PMID- 15945971
TI  - Selection of tests and services to generate revenue for reference laboratories.
AB  - The 1980s have brought heightened awareness of the operating costs of
      immunohematology reference laboratories. Revenues can be increased by raising
      existing charges, expanding services, and acquiring new customers. Selection of
      tests and services to further increase revenue is best made following a thorough
      assessment of community needs and the capabilities and resources of the reference
      Laboratory.

PMID- 15945972
TI  - Cost accounting for blood bank laboratories.
AB  - To meet the challenges of present-day blood banking, laboratory managers and
      supervisors must acquire and use skills in financial management. One such skill
      is cost analysis. Cost analyses vary from simple to complex and are used to
      determine the basic elements contributing to a test cost. Cost analysis can be
      used to identify costs, justify updating laboratory test prices, monitor general
      supply and reagent costs, help in the decision to lease or buy an instrument,
      modify existing test procedures to cut costs, determine staffing needs, and
      assure accurate reimbursement for laboratory services.

PMID- 15945973
TI  - Case report: ABO discrepancy due to vancomycin complicating a transfusion
      reaction investigation.
AB  - A 3-year-old patient with acute myelogenous leukemia developed fever and chills
      during transfusion of packed red cells. A preliminary workup suggested that a
      group AB donor unit had been issued to a Group A patient. However, a discrepancy
      between the ABO group of the original donor unit segment (A) and blood taken from
      the IV tubing (AB) and the patient's pre- and post-transfusion samples (A and AB,
      respectively) suggested mother reason for the weak reactivity of some samples
      with anti-8. The patient's chart revealed that vancomycin, reported to be a cause
      of non-immune agglutination of red cells, had been injected into the IV tubing
      one hour prior to transfusion. Further testing confirmed that the patient's
      febrile response to transfusion was consistent with a nonhemolytic transfusion
      reaction and was unrelated to the drug-induced, pseudo ABO problem.

PMID- 15945975
TI  - Excellent presentation of a method that can be used to evaluate the specificity
      of autoantibodies.

PMID- 15945977
TI  - A review: the Kidd system.

PMID- 15945978
TI  - An example of anti-JMH with characteristics of a clinically significant antibody.
AB  - The authors studied an example of red cell anti-JMH (John Milton Hagen) that
      exhibited several characteristics of a possible clinically significant antibody
      able to cause red cell destruction in vivo. Strong serological reactivity, a
      positive monocyte monolayer assay, and immunoglobulin subclass determination as
      IgG3 all indicate possible ability to destroy red cells. A51Cr-labeled red cell
      survival study was not done as the patient did not require red cell transfusions
      but may be recommended for this patient if transfusions become necessary.

PMID- 15945979
TI  - Red cell antibody identification by solid phase red cell adherence utilizing
      dried RBC monolayers.
AB  - Recent technological advances in the immobilization and drying of red cell
      monolayers for use in solid phase red cell adherence (SPRCA) assays have resulted
      in the development of reagent red cells for antibody screening and identification
      that are stable at mom temperature. Panels consisting of twelve different RBC
      samples dried onto individual microplate wells were evaluated with 176 samples
      whose antibody specificities had previously been determined by conventional
      hemagglutination techniques. Identification tests performed with dried SPRCA
      panels proved to be more sensitive and less time consuming than hemagglutination
      tests. The red cell antigens of dried membranes were shown to be stable and
      reactive following storage for 120 days at mom temperature.

PMID- 15945980
TI  - Tech tip: the use of EDTA when whole blood samples fail to clot quickly.

PMID- 15945985
TI  - Cromer-related blood group antigens and the glycosyl phosphatidylinositol-linked
      protein, decay-accelerating factor DAF (CD55).
AB  - Cromer-related blood group antigens are located on the complement regulatory
      glycoprotein, decay-accelerating factor (DAF). DAF is not detectable on red cells
      from individuals with a Cromernull) phenotype (termed Inab), which is probably an
      inherited condition. DAF is also absent from a subpopulation of red cells (PNH)
      III) from patients with paroxysmal nocturnal hemoglobinuria (PNH), an acquired
      hematological defect. PNH III red cells, like Inab cells, lack all the Cromer
      related antigens described to date.

PMID- 15945986
TI  - A review: the use of monoclonal antibodies in blood banking.

PMID- 15945987
TI  - Microcomputer-generated antigen panel worksheets.
AB  - Many antibody identifications require testing with cells of rare or uncommon
      phenotypes. To expedite the resolution of these identifications, we developed a
      microcomputer database using Lotus 123 to enter antigen phenotypes from our
      frozen cell inventory. Data is entered into a customized screen input form and
      automatically copied to the database The use of an input form protects the
      database from inadvertent errors made while entering data. The database can be
      searched for any combination of red cell phenotypes. When found, the selected
      cells are extracted tu a predesigned worksheet. Panel worksheet forms are created
      with Allways, a software program used in conjunction with Lotus 123, Allways is
      specifically designed to generate quality printouts with a laser printer. The
      program has many formatting features that simplify horizontal and vertical ruling
      for the worksheet. In addition, the program provides degrees of shading to
      highlight specific antigens or entire columns or rows of information. Once the
      worksheet template has been designed, it is automatically saved with the database
      file. More than one worksheet template can be stored in the database file. This
      program reduces the amount of time spent searching through records to find the
      necessary cells for testing, It also reduces potential error in hand copying
      antigen phenotypes to a worksheet. This application can also he used for HLA
      panels.

PMID- 15945988
TI  - Vancomycin-induced neutropenia associated with anti-granulocyte antibodies.
AB  - Neutropenia is a rare complication associated with vancomycin, and the cause of
      this adverse reaction is not well understood. We report a case of vancomycin
      induced neutropenia in which we were able to demonstrate anti-granulocyte
      antibodies. We also report the results of a hone marrow examination along with a
      brief review of the literature.

PMID- 15945989
TI  - Du phenotyping by the rosette technique when the direct antiglobulin test is
      positive.
AB  - The rosette technique provides a simple rapid and accurate procedure for Du
      phenotyping of red blood cells (RBCs) with a positive direct antiglobulin test
      (DAT) due to antibodies other than those of the Rh system. We used Sebring and
      Polesky's rosette technique to test RBCs with positive DATs. Characteristic
      microscopic agglutination was observed for the Du phenotype which was different
      from the mixed-field agglutination seen as positive rosettes in feto-maternal
      hemorrhage (FMH). The microscopic "starry-sky" pattern typical for FMH-positive
      rosettes is easily differentiated from the uniform agglutination produced by the
      D phenotype. The rosette technique was performed on 202 Rh negative cord RBCs out
      of 4815 cord cells with a positive DAT. Parallel testing for Du by the
      chloroquine elution and antihuman globulin (AHG) test was done on 67 of the 202
      cases. Four Du RBCs that were identified by the rosette technique were confirmed
      by the chloroquine Du technique The rosette technique proved to be time saving
      and as sensitive as the routinely performed elution technique for removal of
      antibodies followed by the AHG Du test.

PMID- 15945992
TI  - A review: antibodies with high-titer, low-avidity characteristics.

PMID- 15945991
TI  - Human leukocyte antigens (HLA) class I (Bg) on red cells studied with monoclonal
      antibodies.
AB  - Monoclonal antibodies, capable of detecting monomorphic epitopes on HLA class I
      polypeptides and beta-microglobulin (Beta2-M), have been used by a variety of
      techniques to ascertain the type of structure detected on red blood cells (RBCs).
      Hemgglutination with class I monoclonal antibodies confirmed the reported
      relationship between Bg blood groups and HLA. It also established that the
      expression of HLA on RBCs which do not have nuclei is not normally strong, but
      may be enhanced in patients, notably those with systemic lupus erythematosus
      (SLE). Estimates of the number of class I molecules on mature RBCs by a
      radioligand-binding assay have confirmed that all HLA-B7 (Bga) individuals have
      higher numbers but that SLE patients usually have the most (124/RBC). Class I
      polypeptides were not elevated in the plasma of SLE patients and all RBCs lost
      molecules on aging in the circulation. These two facts suggest that HLA on RBCs
      is not acquired from plasma. when RBCs from SLE patients were immunoblotted with
      monoclonal antibodies, a complete 45 kDa intrinsic transmembrane heavy chain of
      HLA class I and a light chain of 11 kDa (Beta2-M) were detected. Chloroquine
      treatment and acid elution of RBCs did not remove HLA class I but only Beta2-M,
      As most antibodies recognize epitopes that depend on close association of class I
      with Beta2-M, the lost reactivity of treated RBCs may be understood.

PMID- 15945993
TI  - A simple method for inhibiting ABO antibodies in sera used for platelet
      crossmatching.
AB  - Sometimes it is necessary to crossmatch and transfuse ABO-incompatible platelets
      As IgG anti-A and anti-B sometimes react with platelets from group A or B donors,
      these reactions can confuse the interpretation of crossmatching, which is
      designed to detect HLA or platelet-specific antibodies. Methods previously
      described to overcome this problem have been complex. Neutr-ABR, which contains A
      and B blood group substances from porcine and equine sources, can be used to
      neutralize anti-A and/or anti-B in sera used to crossmatch ABO-incompatible
      platelets. This simple technique has been used for many years in red blood cell
      (RBC) serology and involves simply adding 1 volume of Neutr-AB to 5 volumes of
      serum and incubating at room temperature for 5 minutes. In this study, 13 of 65
      (20%) random group O donor sera reacted against random group A platelets and 6 of
      67 (9%) random group O donor sera reacted against random group R platelets. All
      of the anti-A and anti-B reactions were inhibited by Neutr-AB when tested against
      group A or B platelets by solid-phase ELISA. The amount of A antigen on platelets
      and the levels of anti-A in group B or O sera can vary considerably, so we
      investigated the extent of the problem in platelet crossmatching. Sixty percent
      of 20 random group O sera reacted with platelets from a donor, who was selected
      because of the strong A antigen present on the platelets. Eighty-six percent of
      randomly selected group A platelets reacted with a group O serum containing
      strong anti-A. Neutr-AB was found not to inhibit 1 anti-P1A1 and 6 anti-HLA.

PMID- 15945994
TI  - A case report: clinically benign anti-Cs(a).
AB  - Previous reports on the clinical significance of anti- Csa(Cost-Stirling) have
      presented conflicting data. We report our findings, over an 8-month period, of a
      patient whose serum contained anti-Csa and anti-Fya. Nineteen donor units of ABO
      and Rh-matched, Fya-negative red cells, which were crossmatch incompatible, were
      transfused with no clinical, serological, or biochemical evidence of a hemolytic
      transfusion reaction.

PMID- 15945995
TI  - Tech tip: a simple method to remove excess white cells from a leukemia patient's
      sample prior to ZZAP treatment of the red cells.

PMID- 15945997
TI  - Concise review of the Kidd system.

PMID- 15946002
TI  - A case report: IgG autoanti-N as a cause of severe autoimmune hemolytic anemia.
AB  - A 21-year-old white worn was referred for evaluation of hemolytic anemia after a
      9-day history of marked hemoglobinuria, jaundice, and weakness. The patient's
      hematocrit was 18%, despite at least eight transfusions over the previous week,
      and the reticulocyte count was < 1%. Serologic evaluation revealed a weakly
      positive direct antiglobulin test with anti-C3 only The serum contained cold and
      warm-reacting anti-N Dithiothreitol had no effect on either the cold- or the warm
      reacting anti-N activity, and radioimmunoassay with monoclonal anti-IgG was
      strongly positive, indicating that both the cold- and the warm-reacting anti-N
      reactivity resided in the IgG fraction. The patient was treated with N - 'N' +
      red cell transfusions, prednisone, and azathioprine and gradually became
      transfusion independent. Postrecovery typing revealed her red cells to be
      M+N+S+s+. This constitutes the third case of autoimmune hemolytic anemia
      associated with IgG autoanti-N. The marked hemoglobinuria and reticulocytopenia
      are unique features of this case.

PMID- 15946003
TI  - Two cases of autoantibodies that demonstrate mimicking specificity in the Duffy
      blood group system.
AB  - Two transfused Caucasian patients presented with possible delayed transfusion
      reactions. Both patients demonstrated an anti-Fya (Fy1) plus anti-Fyb (Fy2)
      pattern of reactivity in their sera. The patients' red blood cells (RBCs) were
      Fy:1,-2,3. Both had positive direct antiglobulin tests (DAT) with anti-IgG and 
      C3d. The serum antibodies reacted with the patients' RBCs drawn when the DATs
      were negative Both patients' serum samples showed reactivity with Fy:1,-2 (1+),
      Fy:-1,2 (3+), Fy:1,2 (3+) RBCs at the antiglobulin phase (AGT) but were
      nonreactive with Fy: -1, -2 RBCs. The antibodies in both cases were nonreactive
      with papain- or ficin-treated RBCs and reacted with Rhnull RBCs, which ruled out
      anti-Fy3 and anti-Fy 5 respectively. These cases suggest mimicking autoantibody
      specificities in the Duffy system one case may indicate that the degree of
      reactivity is dependent on the Duffy phenotype of the RBCs tested( Fy:-1,2 >
      Fy:1,2 > Fy: 1,-2). An unusual characteristic seen in both of these cases was
      hemolysis in the EDTA cell samples but none In the clotted samples.

PMID- 15946004
TI  - Microcomputer-generated antigen panel worksheets.
AB  - Early reports of anti-Rodgers (anti-Rg) noted that there was an increased number
      of the HLA-B8 phenotype among this group. This HLA type has recently been Linked
      to a C4A (Rg) gene deletion found with increased frequency among systemic lupus
      erythematosus (SLE) patients. Healthy controls (n= 176) and SLE patients (n=102)
      were studied for their HLA haplotype and C4 allotype as well as their Rg
      phenotype Six of 53 white and 3 of 49 black SLE patients were C4A-null and
      Rodgers-negative, a significant difference from controls p=.002). A retrospective
      study of patients who produced ant-Rg showed that one third had symptoms often
      associated with SLE but none had SLE as a primary diagnosis.

PMID- 15946005
TI  - Rapid and simple generation of labels using Lotus 1-2-3.
AB  - A macro-driven Lotus 1-2-3 template is described that allows the rapid generation
      of labels. Use of this template allows flexibility in the design of labels and
      can provide labels during computer "down time."

PMID- 15946007
TI  - A simple method for the removal of contaminating white cells prior to serological
      procedures.

PMID- 15946006
TI  - Tech tip: procedure for rapid antigen screening with LIM reagent.

PMID- 15946008
TI  - An outgrowth of the metric system.

PMID- 15946010
TI  - A review: controversies in blood component use in newborns.
AB  - Advances in the care of the critically ill neonate have necessitated dramatic
      changes in the blood bank's response, especially to the needs of the low-weight
      premature infant. The neonate is now considered a major consumer of blood
      products, and the packaging and administration of these products must he altered
      to suit its specialized needs. The indications and preparations for small-volume
      red blood cell (RBC) transfusions are of particular concern. Small volume RRC
      transfusions are both the most frequently used and the most controversial in the
      treatment of neonates. A review and guidelines for the use of RBCs for the
      perinatal patient are presented.

PMID- 15946011
TI  - Primary immune response to blood group antigens in burned children.
AB  - Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an
      anamnestic immune response. Case reports of DHTRs due to a primary immune
      response are rare. Transfusion reactions occurring in patients on the pediatric
      burn unit from 1981 to September 1988 were reviewed, and additional information
      was obtained for patients for whom a DHTR was documented. Of 62 transfusion
      reactions, 11 were classified as a primary immune response (DHTR), with either a
      positive antibody screen, a positive direct antiglobulin test (DAT), or both.
      None of the 11 patients included in the study had been previously tranfused or
      pregnant. The average number of units transfused prior to antibody identification
      was 19. The average time elapsed between the first transfusion and antibody
      identification was 3.6 weeks. Anti-K and anti-E were the most frequently
      identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and
      hematocrit at the time that a positive DAT was detected. Such changes could not
      be demonstrated for the remaining eight patients. The conclusion was that a DHTR
      may he caused by a primary immune response in burned children more often than
      expected, but DHTR signs and symptoms are often not apparent due to the
      complications of burn trauma.

PMID- 15946012
TI  - Microcomputer software simulating problems in Rh immune globulin prophylaxis and
      hemolytic disease of the newborn.
AB  - Our purpose was to develop educational software that would simulate laboratory
      investigation of problems in Rh immune globulin prophylaxis and hemolytic disease
      of the newborn. An interactive, branching style program was developed using a
      256K Penonal Computer (International Business Machines, Boca Raton, FL). The
      software has been used in over 125 institutions for preprofessional and
      continuing professional education.

PMID- 15946013
TI  - The sensitivity of antibody detection testing using pooled versus unpooled
      reagent red cells.
AB  - Because the sensitivity of antibody detection testing may be reduced when pooled
      reagent red blood cells (RBCs) are used, the American Association of Blood Banks
      (AABB) prohibits the use of pooled reagent RBCs when performing pretransfusion
      antibody detection testing. This restriction imposed upon the use of pooled
      reagent RBCs is based, at least in part, on the belief that pooled reagent RBCs
      are less likely to detect clinically significant antibodies than are sets of
      unpooled reagent RBCs. Little data, however, have been published to support this
      contention. In the present study, the data show a decreased sensitivity for
      antibody detection when pooled reagent RBCs are used. This reduced sensitivity
      could result in failure to detect some clinically significant RBC alloantibodies,
      which might result in the occurrence of overt hemolytic transfusion reactions,
      especially if an indirect antiglobulin test is not performed at the time blood is
      crossmatched.

PMID- 15946014
TI  - Procedural errors in antibody identification.
AB  - In experimental studies of students and line technologists performing antibody
      identification procedures, both groups made errors. These errors included, at
      times, either failing to identify an antibody or misidentifying the
      specficity(ies)A. prospective study was undertaken to identify errors made in a
      laboratory setting. Errors were classified as 1) failing to follow protocol
      (procedural error) or 2) arriving at the wrong answer (misidentification error).
      Over a 1-year period, 1,057 workups were reviewed. There were 41 (3.88%)
      procedural errors and no misidentification errors. In 25 workups (61% of errors),
      the selection of cells m rule out underlying alloantibody(ies) was in error. The
      remaining 16 involved various "slips" (minor mistakes or memory lapses) and
      clerical errors. Based on an analysis of the probable causes of these errors,
      potential solutions include 1) developing computer aids to detect "rule-out"
      errors or missing tests results; 2) providing timely, careful review of workups
      before transfusion; and 3) designing better panel layout and cell selection.

PMID- 15946017
TI  - An invited review: the Rh antigen e, its variants, and some closely related
      serological observations.

PMID- 15946018
TI  - Indicators of clinically significant red cell antibodies produced by sensitized
      lymphocytes in liver transplant patients.
AB  - It has been documented that transplanted livers can carry sensitized lymphocytes
      that subsequently produce red cell antibodies. We evaluated immunohematological
      variables in liver donors and recipients for indicators that might be predictive
      of serological red blood cell (RBC) destruction mediated by the passenger
      lymphocytes. Organ donor sera with antibody scores greater than ( > ) 60
      correlated with a positive direct antiglobulin test (DAT) and need for increased
      RBC transfusion in liver transplant recipients. We therefore propose an antibody
      screen on all potential liver donors and titration of unexpected alloantibodies;
      titration of ABO antibodies of liver donors who demonstrate minor ABO
      incompatibilities with their recipients; and, when needed, transfusion of group O
      RBCs to recipients of livers from donors with minor ABO-incompatibility who have
      antibody scores >60.

PMID- 15946019
TI  - Determining the significance of anti-Kl in hemolytic disease of the newborn
      (HDN).
AB  - Anti-K1 is capable of causing severe hemolytic disease of the newborn (HDN), but
      few cases are seen due to the low frequency of the antigen. A total of 1,215
      pregnancies from 1962 to 1989 were reviewed. There were 404 non-anti-D clinically
      significant antibodies, of which 103 (25%) were anti-K1. Anti-K1 was detected in
      nine of the women at delivery, of whom two had antigen-positive infants who were
      clinically unaffected. Antigen typing was done on 64 of the 85 fathers. Forty
      seven were K - 1 and 17 were K1,2; 21 were unavailable. Antibody titers were done
      on the mothers in the latter two groups. Women with titers <32 were followed by
      titration studies; all delivered clinically unaffected infants, four of whom were
      K:1. Women with titers >32 had amniocentesis performed for optical density values
      (AOD450) or, after November 1987, were offered an alternative test,
      cordocentesis, to type the fetus and to do hemoglobins if the fetus was antigen
      positive. Two women had severely affected infants requiring multiple intrauterine
      transfusions starting at 20-23 weeks. Six others delivered antigen-positive
      infants who did not require transfusions, although all had positive direct
      antiglobulin tests (DAB). We conclude that titration studies are reliable tools
      to evaluate anti-K1 sensitization when the titer is <32. Cordocentesis can detect
      antigen-negative fetuses, which then reduces the need for titrations and
      amniocentesis.

PMID- 15946020
TI  - The sensitivity of antibody detection testing using pooled versus unpooled
      reagent red cells.
AB  - Evaluation of paternity (alleged father, mother, and child) can range from a
      straightforward resolution to a complex problem that cannot be resolved without
      family studies. We present a case of disputed paternity in which tests for
      crossreactive groups (CREcS) and antigen subtypes (splits) within the human
      leukocyte antigen (HLA) system could not be used confidently to prove or disprove
      paternity. Further analysis, red cell enzyme tests, enabled a final verdict and
      confirmed the current reliability of HLA antisera defining splits.

PMID- 15946021
TI  - Use of a modified acid/EDTA elution technique.
AB  - A modification of the acid/EDTA elution technique was recently developed at the
      International Blood Group Reference Laboratory, Bristol, UK. By altering the
      volumes of reagents used, maximization of elution of antibody could be achieved
      without loss of red cell integrity.

PMID- 15946023
TI  - International experts met at the United States Food and Drug Administration.

PMID- 15946024
TI  - A report: "Reagents for the 1990's".

PMID- 15946025
TI  - Phosphatidylinositol-linked red blood cell membrane proteins and blood group
      antigens.
AB  - A new class of membrane proteins has recently been described. Unlike integral
      membrane proteins, which traverse the membrane with one or more hydrophobic
      peptide domains, the peptide domains of these more newly described proteins are
      entirely extracellular and are anchored to the cell membrane via a
      phosphatidylinositol-glycan (GPI) anchor. Erythrocyte membrane proteins of this
      class include proteins with diverse functions; several, however, are complement
      regulatory proteins. Moreover, it is the lack of expression of GPI-anchored
      proteins that is responsible for manifestations of the acquired hematologic
      disease paroxysmal nocturnal hemoglobinuria. Recently, several investigators have
      also demonstrated that a number of erythrocyte blood group antigens reside on
      this class of proteins. These antigens include those of the Cromer blood group,
      JMH, Holley/Gregory, Cartwright, and Dombrock. The biochemical basis for the
      Cromer, JMH, and Holley/Gregory antigens have so far been partly delineated.

PMID- 15946026
TI  - Antibody detection using pooled sera and a solid phase system.
AB  - The purpose of the study was to evaluate the feasibility of substituting the
      Immucor Capture-R solid phase (SP) antibody detection system for our routine
      donor antibody screen. Our routine procedure (RP) used a 12-drop pool of six
      donor sera and one drop of pooled reagent red cells, with 37 degrees C incubation
      and indirect antiglobulin test readings. The SP system was used according to the
      manufacturer's directions except that one drop of the pooled sera (rather than an
      individual serum) was added to each microwell. In parallel tests of 888 donor
      pools and of 70 stored sera containing known alloantibodies, results with SP were
      comparable to results with RP. After implementation of SP for donor antibody
      detection, 1,135 donor pools were tested. Results with SP appeared satisfactory
      when compared to previous records. We concluded that Immucor Capture-R system can
      be used for antibody detection using pooled donor sera.

PMID- 15946027
TI  - The incidence of WESa in 3,072 donors in the United States.
AB  - The rare red cell antigen, WES(a), which is controlled by an autosomal dominant
      gene, was reported by Sistonen et al.(1) to have an incidence in the Finnish
      population of 0.56 percent. A study was undertaken to determine the incidence of
      the WES(a) antigen within the United States. A total of 3,072 donor samples were
      obtained for testing from eight different geographical locations. It was
      determined that the incidence of the WES(a) antigen in the white donor population
      tested was 2 per 1,610 or 0.12 percent and in the black donor population tested,
      7 per 1,460 or 0.48 percent. In the random population the incidence would he 0.29
      percent.

PMID- 15946029
TI  - The use of pooled reagent red cells.

PMID- 15946030
TI  - A comment on "Reagents for the 1990's".

PMID- 15946033
TI  - Is it alloantibody or autoantibody?

PMID- 15946037
TI  - Decreased ABH blood group antigen expression associated with preleukemic
      conditions and acute leukemia: loss of detectable B, then A antigens in a group
      AB patient progressing from a myelodysplastic syndrome to leukemia.
AB  - Decreased or absent expression of blood group antigens is well known to occur in
      acute leukemia. In some carcinomas, the malignant solid tumor cells have also
      been shown to lose normal blood group antigen expression. In both carcinoma and
      hematologic malignancies, these findings have been associated with a more
      aggressive behavior of the neoplasm. A 34-year-old, group AB, Rh positive woman
      was diagnosed with a preleukemic condition, myelodysplastic syndrome, in December
      1988. In April 1989 B antigen expression was markedly decreased, then absent; in
      November 1989 the patient had progressed to acute leukemia. In April 1990 neither
      A nor B antigens could be detected, there was disease progression, and the
      patient died 19 days after A and B antigens were undetectable. Decreased
      expression of normal blood group antigens may prove useful in differentiating
      benign from malignant conditions and may indicate a more grave prognosis.

PMID- 15946038
TI  - Typing of normal and variant red cells with ABO, Rh, and Kell typing reagents
      using a gel typing system.
AB  - In 1989 Lapierre et al. described a novel method of detecting agglutination
      reactions by the use of a Sephadex (DiaMed ID Typing System) gel held in a
      microtube. This report examines the use of gels containing ABO, Rh, and Kell
      system specific antibodies. The anti-A and -B were monoclonal reagents; anti-A,B,
      and those for the Rh and Kell systems were polyclonal. Five hundred and fifty-one
      tests performed for the ABO system detected all but the most weakly reacting
      variants, a detection rate superior to most commercially available reagents. Five
      hundred and thirty samples were typed for Rh antigens. One hundred and twenty
      seven of these were of various D category III through VII types (Dcats) and 154
      were Du>s. The gel system detected all but seven DVI variants and seven Dus. The
      seven DVI variants, from individuals with no anti-D in their sera, gave reactions
      identical to the seven Dus when tested against a panel of over 50 monoclonal IgG
      and IgM anti-Ds. The 554 samples tested for the K1 antigen gave correct results.

PMID- 15946039
TI  - Case reports: red blood cell autoantibodies mimicking alloantibodies.
AB  - The phenomenon of autoantibodies mimicking alloantibodies is rare and
      challenging. This report describes several unusual cases of mimicking
      autoantibodies and reviews the literature.

PMID- 15946040
TI  - Case report and review: alloimmunization, delayed hemolytic transfusion reaction,
      and clinically significant anti-Yt(a) in a patient with Beta-thalassemia/sickle
      cell anemia.
AB  - A 26-year-old female with Beta-thalassemia/sickle cell anemia was admitted to the
      hospital with symptoms of a painful crisis. During the next 4 days her hematocrit
      decreased to 13 percent, and there was reticulocytopenia. She was transfused with
      four units of red blood cells that were microscopically incompatible, and the
      hematocrit increased to 29 percent. Eight days later the patient was readmitted
      with back pain, hemoglobinuria, and a hematocrit of 27 percent. Anti-E, -c, -Jka,
      and -Yta were identified. The direct antiglobulin test was positive, and the
      eluate contained anti-c and -Jka. The patient's hematocrit continued to decrease
      to 14 percent. Transfusions were withheld and the patient recovered uneventfully.
      Separate 51Cr red blood cell survival studies showed significantly shortened
      survival of both autologous and R(1)R(1), Jk(a-), Yt(a+) erythrocytes. This case
      illustrates the complexity of transfusion management in hemoglobinopathy
      patients.

PMID- 15946041
TI  - 51Chromium studies with an IgG1 anti-Yta.

PMID- 15946045
TI  - Review: the Lutheran blood group system-1991.
AB  - The Lutheran blood group system, comprised of 18 antigens with four pairs of
      alleles at closely linked loci, is complex. This article outlines current
      knowledge of the Lutheran system with special reference to recent serologic,
      immunochemical and clinical findings.

PMID- 15946046
TI  - Evaluation of patients with positive direct antiglobulin tests and nonreactive
      eluates discovered during pretransfusion testing.
AB  - Charts from a series of 679 hospital patients with positive direct antiglobulin
      tests (DATs) were reviewed. Sixty-three adult patients who demonstrated positive
      DATs due to IgG only but with nonreactive eluates were selected for further
      retrospective evaluation. Those patients were noted to fall into four distinct
      categories: autoimmune diseases including SLE, renal diseases, multiple myeloma,
      and miscellaneous diseases. In 16 patients for whom serum IgG levels were
      available, a significant correlation existed between the strength of the DAT
      reaction and the serum IgG concentration. Several mechanisms that could be
      responsible for these findings are discussed.

PMID- 15946047
TI  - Clinical correlation of positive direct antiglobulin tests in patients with
      sickle cell disease.
AB  - Serologic findings of immune-mediated hemolytic anemia (autoimmune hemolytic
      anemia and cold agglutinin disease) are not infrequent in patients with sickle
      cell disease and can he clinically significant. Features of sickle cell disease
      that may affect the emergence and intensity of immune-mediated hemolysis include
      the antigenic stimulation of chronic red blood cell (RBC) transfusions, increased
      autoantibody production, RBC membrane defects, and functional asplenism. We
      describe two patients with sickle cell disease and serologic findings of
      autoimmune hemolytic anemia, but only one had increased RBC destruction
      attributed to the autoantibody. That patient's RBCs had IgG and complement on the
      surface, while those of the other patient had IgG without complement. Functional
      asplenism may diminish the role of an IgG autoantibody that does not hind
      complement, since RBCs coated with complement are removed by the liver.
      Therefore, complement-binding autoantibodies may have particular significance in
      immune-mediated hemolysis in patients with sickle cell disease.

PMID- 15946048
TI  - Case report: hemolytic anemia produced by tolmetin.
AB  - Tolmetin, a nonsteroidal anti-inflammatory drug, was found to be the etiologic
      agent in a case of drug-induced hemolytic anemia. A 35-year-old female who had
      ingested tolmetin sporadically in the past took two doses that resulted in acute
      hemolysis. Two days after taking the second dose, she had a hemoglobin of 7.0
      g/dL, increased serum lactate dehydrogenase, reticulocytosis, and indirect
      reacting hyperbilirubinemia. The direct antiglobulin test was weakly positive
      with anti-IgG and anticomplement reagents. The patient's serum was nonreactive
      with reagent red cells in the absence of tolmetin, but addition of tolmetin to
      the serum resulted in strong agglutination of all reagent red cells tested.
      Serologic evaluation of this patient's serum indicated that tolmetin caused
      hemolysis by an immune complex mechanism. Hemolysis subsided and anemia improved
      spontaneously.

PMID- 15946050
TI  - Unexpected activity with monoclonal anti-B reagents.

PMID- 15946049
TI  - Case report: serologic confirmation of paroxysmal cold hemoglobinuria.
AB  - A child with a history of recent viral infection entered the hospital with severe
      anemia, hemoglobinuria, and suspected autoimmune disease. Serologic findings
      included a positive direct antiglobulin test and incompatible crossmatches.
      Extensive studies, including a Donath-Landsteiner test, confirmed paroxysmal cold
      hemoglobinuria. The child was transfused several times with washed red blood
      cells compatible by prewarm technique. Although hemolysis continued after each
      transfusion, he stabilized and went home 5 days after his hospital admission. He
      reportedly made a complete recovery.

PMID- 15946053
TI  - Review: red cell alloantibody formation in the neonate and infant: considerations
      for current immunohematologic practice.

PMID- 15946052
TI  - A Polynesian family showing co-dominant inheritance of normal glycophorin C and
      the Gerbich variant form of glycophorin C.
AB  - Two individuals with the rare Ge:-2-3,4 phenotype (Gerbich type of Gerbich
      negative) were identified in a family of Polynesian descent who reside in the
      Cook Islands. In initial serologic tests, all other family members typed as Ge
      positive, and heterozygous individuals could not be identified. Further studies
      on blood samples from seven members of this Polynesian family by immunoblotting
      and hemagglutination tests on trypsin-treated red blood cells showed that normal
      glycophorin C and the product of the Gerbich allele were inherited in an
      autosomal dominant manner.

PMID- 15946054
TI  - Immune hemolytic anemia following heart-lung transplantation.
AB  - Immune hemolytic anemia due to minor ABO incompatibility between recipient and
      donor is a well-recognized occurrence in kidney and liver transplantation. In
      some cases, the responsible antibodies have been shown to be derived from the
      donor passenger lymphocytes using Gm allotyping. We report a case of acute,
      transient hemolysis following heart-lung transplantation in which serologic and
      Gm allotype studies confirmed the etiology of hemolysis.

PMID- 15946055
TI  - Cytomegalovirus antibody screening on the Olympus PK7100.
AB  - The Olympus PK CMV system (OHA) for the detection of antibodies to
      cytomegalovirus (CMV) was evaluated for use on the Olympus PIC7100 automated
      pretransfusion blood testing instrument. Indeterminate reactions were obtained
      with 18 (1.2%) of the 1,495 samples originally tested, of which 9,6, and 3 were
      OHA positive, indeterminate, and negative, respectively, on retest. The OHA was
      found to have a concordance of 99.7 percent when tested in parallel with the CMV
      Scan latex agglutination test (LAT). There were four discrepant results in the
      1,495 donor plasmas tested by the two methods. Two of the three samples that were
      positive by the UT and negative by the OHA test were also negative with the IMx
      enzyme-linked immunosorbent assay (EUSA) and complement fixation test (CFT). The
      OHA failed to detect antibodies to CMV in a sample that was positive by the IMx
      ELISA, CFT, and LAT. The IMx ELISA, which was regarded as the arbiter of true
      positivity, yielded a sensitivity and specificity of 99.9 percent and 100 percent
      respectively, for the Olympus PK CMV system. Forty percent of 1,807 random blood
      donors in this region bad antibodies to CMV. CMV testing can be performed
      simultaneously with blood grouping and red cell antibody screening on the Olympus
      PK7100.

PMID- 15946056
TI  - Failure to detect a prozoning anti-Fya in the serum of a chronically transfused
      patient.
AB  - A 78-year-old white male presented to our facility with vascular occlusion. He
      was Group A, D-positive, with a negative indirect antiglobulin test (antibody
      screen). Records at our facility, 4 years prior to this admission, indicated a
      history of anti-Fya, and Fy(a-) units were provided. A referring hospital had
      transfused the patient for "chronic anemia" (1-3 units weekly for 2 years), and
      he had received eight units (untested for Fya) immediately prior to his transfer
      to our facility for acute hemorrhage. Only the presence of anti-JH in the Serum
      was documented. To detect possible immune red cell destruction, the patient was
      monitored by our facility at 24-hour intervals with a direct antiglobulin test
      and antibody screen. On day 4, a 4+ anti-Fya was identified in the serum and the
      DAT was negative. Three days later anti-K was also identified. The serologic
      picture remained unchanged for 10 days, when the DAT became positive.
      Concurrently, a mixed-field Fya typing (on the patient's chloroquine diphosphate
      treated cells) was detected. Repeat Fya typing of all units transfused at our
      facility confirmed their FY(a-) status. From the day of admission, eluates on
      every sample, using a low pH technique, showed anti-Fya specificity. Titration of
      the anti-Fya in the sample drawn on admission reacted from a dilution of 4
      through 2,048 but not in neat serum. Although a prozoning phenomenon is uncommon,
      this case study suggests that a prozoning anti-Fya present in the patient's serum
      may have been a contributing factor to his "chronic anemia."

PMID- 15946059
TI  - Effect of enzymes on and chemical modifications of high-frequency red cell
      antigens.
AB  - Enzyme or chemical modification of intact red cells results in the destruction of
      some blood group antigens. The pattern of reactions of an antibody with red cells
      treated with various proteinases, with sialidase, and with the disulfide bond
      reducing agent 2-aminoethylisothiouronium bromide (AET) can aid in antibody
      identification. This information can prove particularly beneficial with
      antibodies to antigens of very high frequency, where antigen- negative cells may
      be difficult to obtain. Provided in this article is a table listing most of the
      authenticated high-frequency red cell antigens and the effect on those antigens
      of trypsin, chymotrypsin, a mixture of trypsin and chymotrypsin, papain, pronase,
      sialidase, and AET.

PMID- 15946060
TI  - Review: polyagglutination.

PMID- 15946061
TI  - Serologic investigation of fatal hemolytic anemia associated with a multiple drug
      history and Rh-like autoantibody.
AB  - A patient who expired during an episode of gross intravascular hemolysis had a
      complex medical history, including renal disease, Coombs positive anemia of
      unclear etiology, recent transfusion, and cholecystectomy. Drug history included
      21 different medications, including penicillin, acetaminophen, procainamide,
      furosemide, sulindac, and tolmetin, all of which have been associated with a
      positive direct antiglobulin test or drug-induced hemolytic anemia. The patient
      had a history of recent use of three chemically similar nonsteroidal anti
      inflammatory drugs: tolmetin (Tolectin), sulindac (Clinoril), and ketorolac
      (Toradol). Only tolmetin and furosemide (Lasix) antibodies were demonstrable in
      the patient's serum at the time of her final admission. The patient's serum at
      final admission contained panagglutinating IgG and IgM antibody with a titer of
      1:80 using a pool of R1R1 and R2R2 screening cells. When tolmetin was added to
      the test system, the titer increased to 1:2,560. The direct antiglobulin test was
      3+ (IgG and C3d,b). Eluates contained an Rh-like antibody compatible only with Rh
      deletion cells, and anti-tolmetin antibodies detected when the drug was added to
      the eluate in the presence of Rh deletion cells. Allogeneic adsorbed sera
      contained anti-tolmetin antibodies with a titer of 1:10 and a weakly reactive IgM
      antibody to furosemide. Antibodies to tolmetin and furosemide were apparent only
      when the drugs were added to sera or eluates, not with drug-coated cells. Because
      of the patient's complex medical history, it was not possible to attribute the
      fatal autoimmune hemolytic anemia solely to drug antibody.

PMID- 15946062
TI  - Case report: mixed-field agglutination in a patient with a weak D antigen
      presenting as a possible fetal-maternal hemorrhage.
AB  - A gravida 1, para O, 17-year-old black female was found on prenatal testing to be
      group O, Du+, the latter test showing many unagglutinated cells. Because of the
      mixed-field appearance, the patient was thought initially to have bad a fetal
      maternal hemorrhage. Additional red cell typings were performed, but no other
      apparent mixed-field reactions were observed. The Kleihauer- Betke test and
      hemoglobin electrophoresis indicated that the mixed-field agglutination was not
      due to a fetal-maternal hemorrhage. Thus, the finding of a mixed-field D typing
      could he explained best by a weak D antigen.

PMID- 15946063
TI  - Unusual occurrence with directed donors.

PMID- 15946064
TI  - A fatal case of tolmetin-induced immune hemolysis, disseminated intravascular
      coagulation, and acute renal failure.

PMID- 15946068
TI  - Review: the LW blood group system.
AB  - The LW blood group system had its origin in the early Rh experiments of the 1940s
      and played an important role in our understanding of hemolytic disease of the
      newborn. Considered for a number of years to be the animal equivalent of the
      human Rh(D) antigen, LW(a) has been shown to be unique. Biochemical studies have
      located the antigen on a different protein from proteins of the Rh antigens;
      however, the interdependence of LW and D still exists. The disappearance of LW
      antigens in various disease states and in pregnancy, associated with production
      of apparent alloantibody, remains puzzling, but this phenomenon may eventually
      help our understanding of the immunology of disease.

PMID- 15946069
TI  - Expression of B and H antigens on red cells from a group B(weak) individual
      studied by serologic and scanning electron microscopic techniques.
AB  - The proposita was classified as B(el), B(y), or B(m), Le(b+) by routine blood
      grouping and by adsorption/elution studies using anti-A and -B hyperimmune
      pregnancy sera. Red cells from the proposita adsorbed as much anti-B from the
      hyperimmune sera as did red cells from normal B individuals, but adsorbed less
      anti-A,B (group O serum). Saliva contained H, but not B, soluble substance. Red
      cells from the proposita and a normal B donor were sensitized with monoclonal A
      and B blood group antibodies immunolabeled with colloidal gold particles, and
      examined in a scanning electron microscope. B antigens were found on more than 95
      percent of normal B cells, but on only 2-3 percent of red cells from the
      proposita. However, when the same cells were sensitized with anti-A,B that
      reacted strongly with B oligosaccharides other than type 2 chains, half of the
      labeled red cells from the proposita were labeled more strongly than any normal B
      cells. Our results explain why red cells from the proposita adsorb significant
      amounts of anti-B and anti-A,B without being agglutinated by these antibodies.
      The results of both adsorption/elution and immunolabeling suggest that the B
      antigen on her cells differs biochemically from that on normal B cells.

PMID- 15946070
TI  - Donor origin Rh antibodies as a cause of significant hemolysis following ABO
      identical orthotopic liver transplantation.
AB  - A group A, D-positive patient underwent orthotopic liver transplantation from a
      group A, D-negative (cde/cde) donor. Anti-D and -E were eluted from the
      recipient's red cells and were found in the recipient's serum 13 days later, at
      which time significant hemolysis developed. These Rh antibodies appear to he
      secondary to passive transfer of sensitized donor lymphocytes, a rare finding
      following liver transplantation.

PMID- 15946071
TI  - Alloimmunization by blood group antigens from bone allografts.
AB  - The purpose of this report is to heighten awareness of the risk of blood group
      antigen sensitization following hone allografting. Two Rh-negative females of
      childbearing age developed multiple antibodies to Rh antigens following
      transplantation of bone from Rh-positive donors. A previous pregnancy and/or
      blood transfusions were ruled out as factors influencing the antibody production.
      It is postulated that red cells or red cell stroma in the allografts stimulated
      the antibody production. Therefore, young, Rh-negative bone allograft recipients
      at risk (especially women) should receive Rh-negative bone allografts.
      Alternatively, they should receive Rh immune globulin at the time of
      transplanting if the allograft is from an Rh-positive donor. Bone allografts
      processed to deplete the hemopoietic marrow and red cells should minimize the
      risk of blood group antibody sensitization.

PMID- 15946077
TI  - Review: Developments in the Kell blood group system.

PMID- 15946073
TI  - Developing computer training programs for blood bankers.
AB  - Two surveys were conducted in July 1991 to gather information about computer
      training currently performed within American Red Cross Blood Services Regions.
      One survey was completed by computer trainers from software developer-vendors and
      regional centers. The second survey was directed to the trainees, to determine
      their perception of the computer training. The surveys identified the major
      concepts, length of training, evaluations, and methods of instruction used.
      Strengths and weaknesses of training programs were highlighted by trainee
      respondents. Using the survey information and other sources, recommendations
      (including those concerning which computer skills and tasks should be covered)
      are made that can be used as guidelines for developing comprehensive computer
      training programs at any blood bank or blood center.

PMID- 15946078
TI  - The P1H antigen and antibody.
AB  - P1H. a newly discovered compound antigen associated with both the ABO and P
      systems, occurs in approximately percent of Natal (South African) blacks. The
      compound antigen, is evident only when the red cells have exceptionally strong
      expression of both and H antigens, and it is apparently a dominant character. The
      antigen is thought to originate by steric rearrangement in the molecule, or to be
      the product of competition between pl and H gene transferases for the available
      paragloboside The corresponding antibody, anti-P1H, has been made by both P1 and
      P2 people and is a weak cold agglutinin It is not adsorbed by red cell, carrying
      either strongly expressed P1 or H antigens but is adsorbed by and eluted from
      P1H+ red cells sensitized by anti- P1H. The antibody is, inhibited by P1 but not
      by H. Lewis, or Sda substances.

PMID- 15946079
TI  - A weak B antigen with serologic reactivity between B1 and B2 red blood cells
      found in a Chinese family.
AB  - During a serologic study on red cell samples from individuals representing three
      generations of a Chinese family, an unusual pattern of reactivity was noted in a
      sample from a daughter of an A1B2 individual. The results of direct ABO grouping,
      titration, and adsorption studies demonstrated that the red blood cells (RBCs)
      from the proposita and two of the proposita's uncles (1) expressed more B antigen
      than group B2 RBCs but less than group B1 RBCs; (2) expressed the B1 antigen but
      at a lower level than group B1 RBCs; and (3) expressed more H antigen than B1
      RBCs but slightly less than B2 RBCs. The saliva from the proposita contained
      soluble B and H antigens, and her serum contained a weak B-gene-specified
      transferase. Serologic reactivity of her RBCs was intermediate between that of B1
      and B2, RBCs. That is similar to reactivity of Aint RBCs, which is intermediate
      between A, and A2 RBCs. The proposita may represent a Bint phenotype.

PMID- 15946080
TI  - Antibody detection errors due to acidic or unbuffered saline.
AB  - Isotonic saline solutions, buffered with potassium phosphate or sodium phosphate
      salts, were evaluated in parallel with unbuffered saline to determine if they
      improved antibody detection by solid phase red cell adherence or hemagglutination
      methods. Saline buffered to a pH of 7.0 to 7.5, when used to suspend red cells or
      to wash sensitized red cells in preparation for the antiglobulin test, produced
      the best positive solid phase and hemagglutination results. The pH range of
      commercially prepared blood bank saline (unbuffered) was found to be 5.8 to 6.8,
      far lower than the desired pH for optimum antibody detection. In the case of
      solid phase assays employing intact, immobilized reagent red cells, saline with a
      pH of 7.0 to 7.5 also eliminated falsely positive results due to the dissociation
      of red cell monolayers from the solid support surface that occurred in the
      presence of unbuffered or acidic saline. These findings indicate that unbuffered
      isotonic saline should not be used in solid phase- or hemagglutination-based
      antibody detection tests. It is recommended that phosphate-buffered saline at a
      pH of 7.0 to 7.5 be employed.

PMID- 15946081
TI  - Compatibility testing problems associated with bovine thrombin-treated plasma.
AB  - Plasma converted to serum by the addition of bovine thrombin prior to
      compatibility testing agglutinated all donor red cells. This finding prompted an
      investigation of bovine thrombin- associated incompatibility that showed that (1)
      thrombin derived from bovine plasma contains IgG antibodies directed against all
      human red cells, and (2) excess (> 50 units/mL) bovine thrombin used for
      conversion of plasma to serum may cause hemagglutination and erroneous serologic
      test results because of the presence of heteroagglutinins.

PMID- 15946083
TI  - Literature review. General (1992).

PMID- 15946082
TI  - The use of computers in teaching clinical laboratory science.
AB  - The Transfusion Medicine Tutor (TMT) has been designed to study the use of
      computers in teaching concepts and problem- solving skills important in the field
      of clinical laboratory science. This system provides students with an opportunity
      to gain experience by solving a wide range of actual cases, and coaches these
      students when they are having difficulties. This system is designed specifically
      to detect and respond to a variety of errors that students may make while solving
      cases, and to suggest more advanced problem-solving methods when appropriate.
      This article describes the concepts behind the design of TMT.

PMID- 15946085
TI  - Review: The Diego blood group system.

PMID- 15946086
TI  - Immune-mediated hemolysis in a postoperative patient Case report: anti-U and
      differential diagnosis.
AB  - We present the differential diagnosis for a Coombs-positive immune hemolysis
      having onset during hospitalization and, in particular, during the postoperative
      period. The stimulus for this article was a delayed hemolytic transfusion
      reaction (DHTR) due to anti-U following open-heart surgery. The initial clinical
      and serologic findings led us to consider other causes of immune hemolysis which
      are reviewed in this article. To our knowledge, this is the fourth case of a DHTR
      due to anti-U to be reported in the medical literature.

PMID- 15946088
TI  - Fy3 and Sl(a) are carried on different red cell membrane proteins.

PMID- 15946087
TI  - Anti-Uz found in mother's serum and child's eluate.
AB  - A saline-reactive antibody, anti-Uz, that reacted stronger with S+ than with S-
      red blood cells (RBCs) and failed to react with U- or ficin-treated RBCs has been
      previously reported. We describe an antibody of similar specificity in the
      postpartum serum of an untransfused woman and the eluate from her fourth child's
      cord RBCs. The mother's RBCs typed S-s+U+, He+(weak), and appeared to have normal
      glycophorin A and B content, as deter- mined by immunoblotting. The direct
      antiglobulin test (DAT) and the autocontrol were negative. Her serum reacted
      stronger with S + RBCs only in the antiglobulin phase, and failed to react with U
      or ficin-treated RBCs. The antibody was adsorbed completely by S-s+U+ RBCs,
      proving that anti-S was not present. Monocyte monolayer assay results with S+s-U+
      and S-s+U+ RBCs indicated that transfusion of incompatible blood would not result
      in significant hemolysis. The child's cord RBCs typed S-s+. The DAT was 3+ with
      anti-IgG, and an eluate prepared from these RBCs had the same reactivity as the
      maternal serum. The child showed no clinical signs of hemolytic disease of the
      newborn. In contrast to previous reports, these results suggest an immune form of
      anti-Uz.

PMID- 15946089
TI  - Identifying blood group antibodies...can a computer help?
AB  - Antibody identification is one of the last areas of laboratory medicine to
      embrace computerization. This is due in part to the complex nature of antibody
      identification. Until recently, computer programs written to assist with antibody
      identification have been slow and cumbersome. However, technological advances in
      computer hardware have greatly improved the response time for these applications.
      Still, blood bank technologists sometimes shun assistance from the computer
      because they consider anti- body investigation as an intellectually stimulating
      aspect of their job that they do not wish to turn over to a computer. Computer
      programs for antibody investigation are probably most useful for technologists
      who perform antibody investigations infrequently. They can also be invaluable for
      experienced technologists performing complex investigations. When integrated with
      a computerized blood bank record-keeping system, antibody investigation software
      can improve storage and retrieval of test results. Database applications for
      retrieving rare cells and sera offer the potential to improve the productivity
      and capability of any anti- body investigation laboratory. And word processing
      applications greatly enhance the potential for generating meaningful reports of
      test results.

PMID- 15946090
TI  - Literature review. Low-frequency antigens (LFAs).

PMID- 15946092
TI  - Review: Modern molecular genetic techniques.

PMID- 15946093
TI  - Six monoclonal antibodies to the CD59 antigen.
AB  - CD59 defines an N-glycosylated glycoprotein expressed on various hemopoietic
      cells. It is anchored to the cell membrane by a glycosylpbospbatidylinositol
      linkage and restricts the action of homologous complement. Monoclonal antibodies
      2/24, 182, Fib75.1, BRIC 229, MEM-43, and YTH 53.1 were compared by
      immunoblotting against normal erythrocyte ghosts. All six stained a diffuse band
      of 17-25 kDa, but BRIC 229 also detected bands at 35 and 80 kDa. 2/24 reacts with
      all red blood cells (RBCs) tested, including Rhnull; Ob; ii; Ko; FY:-1,-2,-3; JK:
      1,-2,-3; S-s-U-; p; CO:-1,-2; Yt(a-); Jr(a-); Vel-; At(a-); Cr(a-); GE:-2,-3;
      Wr(a+b+ MkMk; Jo(a-); and Lan-. 2-aminoethylisotbiouronium bromide treatment of
      erythrocytes destroyed blotting and serologic reactivity of all six antibodies.
      Pronase treatment reduced serologic reactivity and blotting ability of all
      antibodies except BRlC 229. Reactivity of all six antibodies was reduced with
      RBCs from paroxysmal nocturnal hemoglobinuria patients. Flow cytometric analysis
      was used to demonstrate that 182, Fib75.1, BRIC 229, YTH 53.1, and MEM-43
      competitively inhibited the binding of 2/24 to RBCs, thus demonstrating that all
      six antibodies detect epitopes on the same molecule.

PMID- 15946094
TI  - Reactive lysis--a phenomenon of delayed hemolytic transfusion reactions.
AB  - A 62-year-old female with Gaucher's disease demonstrated alloanti-c on
      pretransfusion testing. She was transfused with five units of c-negative red
      blood cells (RBCs) preoperatively and intraoperatively. The hemoglobin (Hb) level
      was slightly lower initially, hut was markedly lower on day 10 posttransfusion.
      Serologic results indicated a delayed hemolytic transfusion reaction (DHTR) due
      to alloanti-s, -Fya, and -Jkb, present both on the RBCs and in the serum. As late
      as day 35 posttransfusion, a mixed-field anti-IgG direct antiglobulin test (DAT)
      indicated that there were two cell populations present. The DAT remained positive
      with anti-C3b, -C3d throughout the course of the reaction. Because of the
      substantially lower Hb and the severity of symptoms, immunologic clearance of the
      antigen-positive donor RBCs was expected. However, we demonstrated their
      persistence. Our data corroborates the observation that complement activation
      occurring during DHTRs can result in the hemolysis of innocent bystander
      (autologous) cells.

PMID- 15946095
TI  - Antibody screening and direct antiglobulin testing using BioVue column
      agglutination technology versus standard tube tests.
AB  - The BioVue column agglutination technology (CAT) was evaluated simultaneously
      with standard tube test (STT) methodology for use in indirect antiglobulin
      testing (IAT) and direct antiglobulin testing (DAT). One thousand thirty-five
      blood specimens were used for the IAT comparison, and 44 blood specimens were
      used for the DAT comparison. Both polyspecific antiglobulin and anti- IgG
      antiglobulin reagents were used in the tube testing and the CAT testing. For IAT,
      sensitivity was 100 percent for CAT and 99.6 percent for STT; sensitivity was
      97.9 percent for CAT and 100 percent for STT. In addition, a 67 percent labor
      savings was realized with CAT versus STT. Specificity and sensitivity of both
      methodologies were 100 percent for the DAT. BioVue proved to be a reliable and
      efficient alternative to standard test tube methods for doing IATs and DATs.

PMID- 15946097
TI  - Literature reviews. General (1992-1993).

PMID- 15946096
TI  - Case report: A time study of management of a chronically transfused patient with
      multiple antibodies.
AB  - This case report describes laboratory management of a chronically transfused
      sickle cell anemia patient with multiple antibodies and the time involved in
      providing compatible red cells for transfusion. Time was evaluated using the
      laboratory workload record ing method of the College of American Pathologists.
      Red cell units were sent to the hospital within 24 to 48 hours from receipt of a
      referral sample, despite a workload recording time in excess of 15 hours for a
      typical sample.

PMID- 15946099
TI  - Review of a terminology proposed to supersede Miltenberger.

PMID- 15946100
TI  - Review: Hemolytic disease of the newborn.

PMID- 15946101
TI  - A possible relationship between colorectal carcinoma and ABO/Lewis blood groups.
AB  - The incidence of colorectal carcinoma was compared with the incidence of ABO and
      Lewis blood groups. The raw data showed the known overrepresentation of the Le(a
      b) phenotype, but also suggested an association of colorectal carcinoma with the
      Le(a-b+) phenotype in group O individuals. When the data were adjusted by taking
      into account the known loss of Lewis antigens by Lewis-positive patients, this
      association could be shown to be statistically significant. These results may
      indicate involvement of the secretory H antigen in colorectal carcinoma.

PMID- 15946102
TI  - En(a-) phenotype in a Japanese blood donor.
AB  - The first Japanese En(a-) individual (T.N.) was found by screening red cells from
      250,000 Japanese blood donors with monoclonal anti-Ena. His serum contained no
      atypical antibodies and his partial red cell phenotype was M-N-S+s-, although a
      trypsin- resistant N antigen was detected. His red cells were En(a-) and Wr(b-),
      as determined by various human and mouse monoclonal antibodies. The absence of
      glycophorin A (GPA) and the presence of apparently normal glycophorin B (GPB)
      were demonstrated by immunoblotting with antibodies to the extracellular and
      cytoplasmic domain of GPA and to epitopes common to GPA and GPB. Sialic acid
      levels of T.N.'s intact red cells were substantially lower than those of control
      MN cells. Serologic tests suggested that both of T.N.'s parents were heterozygous
      for a recessive GPA deficiency gene.

PMID- 15946105
TI  - Donor screening with anti-AnWj.

PMID- 15946103
TI  - Red cell antigen stability in K3EDTA.
AB  - Commercial blood grouping reagents are not approved for testing EDTA
      anticoagulated blood specimens that are more than 48 hours old. Many studies on
      the stability of blood group antigens in other anticoagulants have been reported,
      but none are available for EDTA. This study was undertaken to assess whether
      current commercially available blood grouping reagents give acceptable reactions
      with red cell antigens when the cells are stored for mended periods in EDTA We
      defined acceptable reaction strength to be 2+ (score 8). As expected, the A, B,
      and D reactions were very stable with red cells stored for 60 days. All antigens
      except Lea exhibited 2+ (score 8) or greater reactions at day 14, and at day 2 1
      only the Lea, Fyb, and e antigens were less than 2+. On day 60, twelve of twenty
      one antigens tested still exhibited 2+ or greater reactions. This study shows
      that antigen reactivity for red cells collected and stored in EDTA is at least
      equal to that for clotted specimens These red cells can be used for reliable
      antigen typing for at least 14 days, and even longer for most antigens.

PMID- 15946106
TI  - Literature reviews. General (1993).

PMID- 15946107
TI  - Are health education meetings effective in recruiting women in cervical screening
      programmes? An innovative and inexpensive intervention from the island of Crete.
AB  - INTRODUCTION: Cervical screening programs have been introduced in many countries
      and are generally regarded as the most appropriate and effective method currently
      available for preventing cervical cancer. Although action has been undertaken by
      some rural practitioners, especially by district midwives, there are still few
      published data on the effectiveness of community-oriented cervical screening
      programs in Greece. OBJECTIVE: To explore an innovative approach in a primary
      care setting in rural Crete. This study reports on the effectiveness of a health
      education meeting in recruiting women for a cervical screening program. METHODS:
      At a centre for the elderly, 16 women participated in an educational discussion
      meeting organised to promote cervical screening. The women who participated in
      the discussion meeting were invited to organise a group visit to a rural primary
      healthcare centre, in order to be screened as a team during the following 15
      days. The theoretical model underpinning the development of this intervention was
      based on the 'social learning theory'. Emphasis was placed up individual and
      social responsibility regarding cervical cancer. RESULTS: A total number of 48
      women (average age 62 years) including all those who participated in the
      educational discussion meeting, visited the Spili Health Center, Crete, 15 days
      after the discussion meeting. The main finding was the high compliance rate of
      the women who participated in the educational discussion meeting, resulting in
      recruiting all the initial participants. Moreover, the lay women who participated
      in the small group discussion meeting, in the capacity of key messengers
      convinced an additional 32 women to participate in a screening program for
      cervical cancer as members of a team, rather than individually. The majority
      (52.1%, n = 25 out of 48) of the women had not been previously screened for
      cervical cancer. CONCLUSIONS: Health education is an important factor in the
      process of health promotion, and health professionals should consider the
      dynamics of a specific group in order to carry out their work effectively.
      Awareness of the special characteristics of an individual as a member of a
      defined group can contribute to increasing the motivation for participation in
      health programs as a member of that group. It is suggested that more educational
      programs take place in rural Crete in order to augment the compliance rate of
      women in cervical screening programs.

PMID- 15946108
TI  - Do benefits accrue from longer rotations for students in Rural Clinical Schools?
AB  - INTRODUCTION: The Australian Government has provided funding for Rural Clinical
      Schools (RCS) to provide substantial rural clinical experience to medical
      students. The strategy aims to acculturate students into rural living with the
      intended long-term outcome of increasing the availability and viability of rural
      health services. When evaluators from two of the Rural Clinical Schools discussed
      findings and insights relating to rural rotations from their in-depth evaluation
      studies of their respective schools they found a range of similarities. This
      article is a collaboration that articulates parallel findings from evaluations
      over 2 years, using three different approaches to students' placements across the
      two RCS: (1) students based long term in one centre (with only a few days away at
      a time); (2) students based long term in one centre with short-term rotations of
      3-6 weeks away from home base; and (3) week rotations without a home base.
      METHOD: The two RCS, as part of their initial establishment, put comprehensive
      internal evaluation processes in place, including the employment of dedicated
      evaluators extant from the teaching and assessment of the rural medical
      curriculum. Data were collected and analysed according to standard education
      evaluation procedures. RESULTS: Home-base preference: most students preferred
      having a home base in one centre and having as little time as possible away from
      that centre, while recognising that sometimes the requirement to go and learn
      elsewhere was useful. The reasons for this were three-fold: academic, clinical
      and social. Academic benefits: students enjoyed the excellence of teaching and
      learning opportunities in their rural sites and did not want their discipline of
      learning interrupted by what they perceived as unnecessary change. Students with
      a home base used their learning opportunities qualitatively differently from
      those students who had 6 week rotations. Their learning became self-directed and
      students sought opportunities to extend and consolidate areas of need. Clinical
      benefits: contributions to the clinical team: students in their clinical years
      want to feel useful and to be allowed to become contributors to the medical care,
      even as they are learning. A longer rotation allows them to become known to their
      teachers who are then able to easily assess the type of contribution that is
      appropriate for their students to undertake. Students then become full
      participating members of the healthcare team, rather than observing learners.
      Social benefits: all students with a home base actively participated in a wide
      range of community activities outside their role as medical students. Those
      students undertaking short rotations without a home base seldom connected in the
      same way to any rural community. CONCLUSION: Evaluation from these two RCS has
      shown that short rotations are likely to be less optimal than longer rotations
      for meeting the broader goals of the RCS to build future workforce capacity. Our
      results suggest that one opportunity to acculturate students into the rural
      lifestyle is lost when students' placements are insufficiently long for them to
      put down roots in their community, and to understand how to 'live' there more
      broadly. Good rural experiences and teaching and learning opportunities are not
      sufficient in themselves. Students' emotional attachment to rural living comes
      from experience related to time and the connection to local people that comes as
      a result of time spent in the community. Students on short rotations do not make
      that local connection.

PMID- 15946109
TI  - The California active aging community grant program: translating science into
      practice to promote physical activity in older adults.
AB  - BACKGROUND: Attempts to study the translation of evidence-based physical activity
      interventions in community settings are scarce. PURPOSE: This project was an
      investigation of whether 13 diverse local lead agencies could effectively
      implement a choice-based, telephone-assisted physical activity promotion program
      for older adults based on intervention models proven efficacious in research
      settings. METHODS: At baseline, participants developed their own physical
      activity programs through an individualized planning session based on preference,
      health status, readiness to change, and available community resources.
      Thereafter, participants received regular telephone calls over a 1-year period
      from a trained staff member or volunteer support buddy. Additional program
      components consisted of health education workshops, newsletters, and group-based
      physical activities. Self-report data on caloric expenditure due to all and
      moderate or greater intensity physical activities were collected from 447
      participants (M age = 68 +/- 8.6 years). RESULTS: A significant increase (p < or
      = .0001) from baseline to midintervention and intervention endpoint was observed
      for total weekly caloric expenditure (Mdn change = 644-707 kcal/week) and
      moderate or greater weekly caloric expenditure (Mdn change = 149-265 kcal/week),
      as well as for weekly physical activity duration and frequency. These changes
      were observed in participants across all sites. CONCLUSIONS: The increases in
      weekly caloric expenditure were commensurate with findings from several previous
      randomized clinical trials. The utilization of community agency staff and
      volunteers receiving basic training to implement essential program components
      proved feasible. Very favorable levels of program satisfaction expressed by
      community staff, volunteer support buddies, and participants, combined with the
      significant increases in physical activity, warrant further dissemination of the
      intervention model.

PMID- 15946110
TI  - The relationship between smoking history and current functioning in disabled
      community-living older adults.
AB  - PURPOSE: This study was conducted to determine characteristics associated with
      continued cigarette use in frail older adults and to examine how smoking history
      relates to current psychiatric, cognitive, and occupational functioning. METHODS:
      Archival records were gathered for 1,064 patients (69% women) who entered On Lok
      SeniorHealth Services between January 1996 and December 2000. Participants were
      interviewed on program entry and assessed for smoking history, depressive
      symptoms, affective disorders, cognitive functioning, alcohol use, and physical
      functioning (activities of daily living [ADLs] and instrumental ADLs). Cross
      sectional analyses were conducted to examine functioning at enrollment relative
      to smoking history. RESULTS: Smoking history was related to age at program entry,
      with current smokers entering On Lok at an earlier age than former or never
      smokers. Current smokers were more likely to be male, to be of Caucasian or
      African American descent, to consume alcohol on a regular basis, and to be more
      independent on ADLs. Specifically, they were more independent on tasks related to
      their capacity to procure cigarettes or continue smoking, including shopping,
      using transportation, managing money, dressing themselves, and walking. Smoking
      history was related to depression, with symptoms lower for current and former
      smokers. CONCLUSIONS: Current smokers present for services at an earlier age and
      have higher levels of independence on ADLs instrumental to nicotine use. Data
      indicate characteristics associated with continued smoking and provide a
      foundation for targeting older individuals for cessation efforts.

PMID- 15946111
TI  - Diagnosis of hypertension and high blood pressure levels negatively affect
      cognitive function in older adults.
AB  - BACKGROUND: Hypertension is associated with diminished performance on tests of
      cognitive function. The degree to which those diagnosed with hypertension have
      controlled blood pressure (BP) levels may be a critical determinant of cognitive
      outcomes. Persons with hypertension and poorly controlled BP are likely to
      display the worst performance on cognitive tests. PURPOSE: The purpose is to
      examine potential interactive relations of hypertension diagnostic status and
      current BP levels to cognitive function. METHODS: Participants were 101 healthy
      older adults (ages 53-84, 62% male, 90% White, 29% diagnosed with hypertension)
      who engaged in biomedical and neuropsychological assessment. RESULTS: After
      statistical adjustment for age and education, persons with high BP performed more
      poorly than those with normal BP on the Visual Reproductions-Immediate and
      Delayed Recall and the Grooved Pegboard tests. Diagnosed hypertension was related
      to poorer performance on the Grooved Pegboard tests. An interaction of diagnosed
      hypertension and BP level revealed that those diagnosed with hypertension and
      also having poorly controlled BP levels performed least well on the Grooved
      Pegboard tests and the Trail Making Test-Part A. CONCLUSION: Irrespective of
      prior diagnostic status, individuals with high BP displayed compromised
      performance on tests of nonverbal memory, motor speed, and manual dexterity.
      However, as compared to the other groups, those diagnosed with hypertension and
      also having poorly controlled BP elevation were most vulnerable to difficulties
      on tests of perceptuo-motor speed, motor speed, and manual dexterity. These
      findings suggest the need for increased attention to preventative efforts with
      respect to BP assessment and control in older adults to help preserve cognitive
      function.

PMID- 15946112
TI  - Comparing participants and nonparticipants recruited for an effectiveness study
      of nicotine replacement therapy.
AB  - BACKGROUND: Interventions for smoking cessation have been typically evaluated on
      reactively recruited samples in clinical trials (efficacy trials). However, to
      have an impact on smoking rates in a general population, the intervention should
      also be evaluated with proactively recruited representative samples
      (effectiveness trials). PURPOSE: The characteristics of participants and two
      groups of nonparticipants recruited for a population-based nicotine replacement
      therapy study were compared. METHODS: All members of a large New England
      Veterans' Administration Medical Center were contacted, and interviews were
      completed with 3,239 identified smokers (at least 10 cigarettes per day). At the
      end of the interview, all smokers were offered participation in a multiple
      intervention study. Of the interviewed smokers, 2,915 verbally agreed to
      participate in the study (90%). Of those who gave initial verbal consent, 2,054
      returned the written informed consent form and became participants (70%).
      RESULTS: The participants (full consent group) differed significantly from both
      nonparticipant groups-that is, the smokers who were interviewed but declined
      participation by active refusal (survey only group) and those who gave verbal
      consent but passively refused participation by failing to return the written
      consent form (verbal consent only group). Participants were more likely to be
      married, younger, and female; to live with others; and to have previously used or
      considered using nicotine replacement therapy. The survey only group was also
      more likely to be in the precontemplation stage (54%), whereas the participants
      were more likely to be in the contemplation (46%) or preparation stage (35%). The
      verbal consent only group was intermediate of the other two groups in stage-of
      change characteristics. CONCLUSIONS: An important finding was that it is possible
      to recruit a large proportion of a sample of identified smokers to an nicotine
      replacement therapy study. However, the participants are likely to differ in
      significant ways from those who either actively or passively decline
      participation.

PMID- 15946113
TI  - Ethnicity, sense of coherence, and tobacco use among adolescents.
AB  - BACKGROUND: Prevention of youth smoking has great potential to improve the health
      of Americans. There is limited information about correlates of tobacco use among
      adolescents from ethnic minority groups, especially Asians, Pacific Islanders,
      and Native Hawaiians. PURPOSE: This article examines the relationships among
      ethnicity, sense of coherence (SOC), and tobacco use. METHODS: We conducted a
      baseline survey of a cluster randomized tobacco prevention trial in public middle
      schools in Hawaii with a multiethnic sample of 3,438 seventh-grade students.
      RESULTS: Ethnic differences in smoking prevalence were very large, with high
      smoking rates among Native Hawaiian/Pacific Islander, White, and Filipino
      students and with low rates among Japanese and Chinese students. Higher SOC
      scores predicted significantly lower risk of having ever smoked and of smoking in
      the past 30 days. SOC was most strongly related to ever smoking among Filipino,
      Hawaiian/Pacific Islander, and White students; Japanese students experienced the
      strongest protective effect from SOC for past-month smoking. CONCLUSIONS: The
      results suggest that SOC is strongly associated with tobacco use among this age
      group. It will be important to examine whether SOC can be improved by an
      intervention program and whether increases in SOC are associated with reduced
      smoking.

PMID- 15946114
TI  - Physical activity as a substitute for sedentary behavior in youth.
AB  - BACKGROUND: Youth may choose to be sedentary rather than physically active.
      PURPOSE: The purpose of this study was to use behavioral economics methods to
      investigate how experimental changes in the amount of sedentary behaviors
      influenced physical activity. METHODS: Fifty-eight 8- to 16-year-old youth were
      studied in a within-subject crossover design with three 3-week phases: baseline,
      increasing, and decreasing targeted sedentary behaviors by 25% to 50%. RESULTS:
      At baseline, boys were more active than girls (518.9 vs. 401.2 accelerometer
      counts/min, p = .02), and obese youth more sedentary than nonobese youth (240.5
      vs. 174.4 min/day, p = .003). During the increase sedentary behavior phase,
      targeted sedentary behaviors increased by 52.1%, with girls increasing sedentary
      behaviors more than boys (114.7 vs. 79.8 min/day, p = .04). Physical activity
      decreased (-48.3 counts/min, p < .01) when sedentary behaviors increased, with
      obese youth decreasing total and moderate to vigorous physical activity (MVPA)
      more than nonobese youth (-110.4 vs. 8.9 counts/min, p < .001; -3.3 vs. -.03 %
      MVPA, p = .013). During the decrease sedentary behavior phase, targeted sedentary
      behaviors decreased by 55.6% from baseline as nonobese youth increased physical
      activity, whereas obese youth decreased physical activity (55.8 vs. -48.0
      counts/min, p = .042; 1.1 vs. -2.1% MVPA, p = .021). Youth who substituted
      physical activity when sedentary behaviors were increased had greater
      standardized body mass index (z-body mass index = 1.4 vs. 0.4, p = .018), whereas
      youth who substituted physical activity when sedentary behaviors were decreased
      were less active at baseline (396.1 vs. 513.7 counts/min, p = .035). CONCLUSIONS:
      Behavioral economics provides a methodology to understand changes in physical
      activity when sedentary behaviors are modified and to identify factors associated
      with substitution of physically active for sedentary behaviors.

PMID- 15946115
TI  - Differentiated roles of social encouragement and social constraint on physical
      activity behavior.
AB  - BACKGROUND: Social support is, in general, positively associated with exercise
      behavior. However, social influence may not always be helpful and may sometimes
      lead to obligation or a sense of intrusion rather than encouragement or
      assistance. PURPOSE: The objective was to determine relationships among different
      types of social influence (social encouragement and social constraint) and
      exercise motivation and exercise behavior. METHOD: Structural equation modeling
      was used to investigate relationships among exercise and social influence
      variables. RESULTS: A model was found to fit the data well in which social
      encouragement had an indirect association with exercise behavior through
      motivational variables. Social constraint was associated with only one aspect of
      exercise motivation--"have to", or obligatory, commitment--and had no direct or
      indirect association with exercise behavior. CONCLUSIONS: These findings
      emphasize the importance of social influences that promote desirable behaviors in
      contrast to those that pose constraints on the failure to perform desirable
      behaviors.

PMID- 15946116
TI  - Affect and pain in rheumatoid arthritis: do individual differences in affective
      regulation and affective intensity predict emotional recovery from pain?
AB  - BACKGROUND: Individual differences in adaptation to rheumatoid arthritis are not
      fully accounted for by illness severity or duration of symptoms. PURPOSE: In this
      study, we assessed differences in affect regulation and affect intensity as
      variables that might be important for identifying women with rheumatoid arthritis
      who are resilient versus those who have disrupted moods following pain
      exacerbations. METHOD: Specifically, affective regulation, affect intensity,
      active coping, neuroticism and weekly reports of pain, positive affect, and
      negative affect were assessed in a sample of 81 women diagnosed with rheumatoid
      arthritis. RESULTS: Our results indicated that affective regulation, affect
      intensity, and active coping played important but distinct roles in the ebb and
      flow of negative and positive affect. In particular, active coping was related to
      positive affect, whereas affective regulation and affect intensity showed
      interactive effects, moderating the prospective relationship between pain and
      negative affect and pain and positive affect. CONCLUSION: Overall, this study
      suggests that recovery from rheumatoid arthritis pain can be swift, except for
      those women who have difficulty regulating strong unpleasant affect.

PMID- 15946117
TI  - Diabetes self-management among low-income Spanish-speaking patients: a pilot
      study.
AB  - BACKGROUND: The prevalence of type 2 diabetes and diabetes-related morbidity and
      mortality is higher among low-income Hispanics when compared to that of Whites.
      However, little is known about how to effectively promote self-management in this
      population. PURPOSE: The objectives were first to determine the feasibility of
      conducting a randomized clinical trial of an innovative self-management
      intervention to improve metabolic control in low-income Spanish-speaking
      individuals with type 2 diabetes and second to obtain preliminary data of
      possible intervention effects. METHODS: Participants for this pilot study were
      recruited from a community health center, an elder program, and a community-wide
      database developed by the community health center, in collaboration with other
      agencies serving the community, by surveying households in the entire community.
      Participants were randomly assigned to an intervention (n = 15) or a control (n =
      10) condition. Assessments were conducted at baseline and at 3 months and 6
      months postrandomization. The intervention consisted of 10 group sessions that
      targeted diabetes knowledge, attitudes, and self-management skills through
      culturally specific and literacy-sensitive strategies. The intervention used a
      cognitive-behavioral theoretical framework. RESULTS: Recruitment rates at the
      community health center, elder program, and community registry were 48%, 69%, and
      8%, respectively. Completion rates for baseline, 3-month, and 6-month assessments
      were 100%, 92%, and 92%, respectively. Each intervention participant attended an
      average of 7.8 out of 10 sessions, and as a group the participants showed high
      adherence to intervention activities (93% turned in daily logs, and 80% self
      monitored glucose levels at least daily). There was an overall Group x Time
      interaction (p = .02) indicating group differences in glycosylated hemoglobin
      over time. The estimated glycosylated hemoglobin decrease at 3 months for the
      intervention group was -0.8% (95% confidence intervals = -1.1%, -0.5%) compared
      with the change in the control group (p = .02). At 6 months, the decrease in the
      intervention group remained significant, -0.85% (95% confidence intervals = -1.2,
      -0.5), and the decrease was still significantly different from that of the
      controls (p = .005). There was a trend toward increased physical activity in the
      intervention group as compared to that of the control group (p = .11) and some
      evidence (nonsignificant) of an increase in blood glucose self-monitoring in the
      intervention participants but not the control participants. Adjusting for
      baseline depressive scores, we observed a significant difference in depressive
      symptoms between intervention participants and control participants at the 3
      month assessment (p = .02). CONCLUSIONS: Low-income Spanish-speaking Hispanics
      are receptive to participate in diabetes-related research. This study shows that
      the pilot-tested diabetes self-management program is promising and warrants the
      conduct of a randomized clinical trial.

PMID- 15946118
TI  - Perceptions of positive meaning and vulnerability following breast cancer:
      predictors and outcomes among long-term breast cancer survivors.
AB  - BACKGROUND: Survival rates for women with early-stage breast cancer have
      increased significantly in recent years. However, little is known about the long
      term impact of the cancer experience on women's psychological functioning.
      Theoretical and descriptive accounts suggest that cancer may evoke both
      perceptions of vulnerability and positive meaning, with potentially different
      effects on mental health. PURPOSE: This study was designed to evaluate the
      prevalence and stability of these perceptions in a large sample of breast cancer
      survivors, to identify their antecedents, and to determine their impact on long
      term adjustment. METHODS: Breast cancer survivors (N = 763) were assessed
      longitudinally at 1 to 5 years and 5 to 10 years postdiagnosis. Participants
      completed surveys assessing perceptions of positive meaning and vulnerability and
      standard measures of psychological adjustment and quality of life. RESULTS: The
      majority of women reported positive changes in outlook and priorities as well as
      feelings of vulnerability at both assessment points. Consistent with hypotheses,
      results showed that perceptions of positive meaning and vulnerability were
      positively correlated and were both associated with factors that increased the
      disruptiveness of the cancer experience. Vulnerability was strongly associated
      with negative affect, whereas meaning was associated with positive affect in
      cross-sectional and longitudinal analyses. CONCLUSIONS: Results suggest that a
      cancer diagnosis may lead to enduring feelings of vulnerability as well as
      positive changes in meaning; however, these perceptions have very different
      mental health correlates.

PMID- 15946122
TI  - Role of peroxisome proliferator-activated receptor gamma in amyloid precursor
      protein processing and amyloid beta-mediated cell death.
AB  - Recent data indicate that PPARgamma (peroxisome proliferator-activated receptor
      gamma) could be involved in the modulation of the amyloid cascade causing
      Alzheimer's disease. In the present study we show that PPARgamma overexpression
      in cultured cells dramatically reduced Abeta (amyloid-beta) secretion, affecting
      the expression of the APP (Abeta precursor protein) at a post-transcriptional
      level. APP down-regulation did not involve the pathway of the secretases and
      correlated with a significant induction of APP ubiquitination. Additionally, we
      demonstrate that PPARgamma was able to protect the cells from H(2)O(2)-induced
      necrosis by decreasing Abeta secretion. Taken together, our results indicate a
      novel mechanism at the basis of the neuroprotection shown by PPARgamma agonists
      and an additional pathogenic role for Abeta accumulation.

PMID- 15946123
TI  - A novel method for observing proteins in vivo using a small fluorescent label and
      multiphoton imaging.
AB  - A novel method for the fluorescence detection of proteins in cells is described
      in the present study. Proteins are labelled by the selective biosynthetic
      incorporation of 5-hydroxytryptophan and the label is detected via selective two
      photon excitation of the hydroxyindole and detection of its fluorescence emission
      at 340 nm. The method is demonstrated in this paper with images of a labelled
      protein in yeast cells.

PMID- 15946125
TI  - Biliary access during endoscopic retrograde cholangiopancreatography: how to
      precut and a word of caution!

PMID- 15946124
TI  - Zn2+-induced reversible dissociation of subunit Rpn10/p54 of the Drosophila 26 S
      proteasome.
AB  - In the presence of Zn2+, the Drosophila 26 S proteasome disassembles into RP
      (regulatory particle) and CP (catalytic particle), this process being accompanied
      by the dissociation of subunit Rpn10/p54, the ubiquitin receptor subunit of the
      proteasome. The dissociation of Rpn10/p54 induces extensive rearrangements within
      the lid subcomplex of the RP, while the structure of the ATPase ring of the base
      subcomplex seems to be maintained. As a consequence of the dissociation of the
      RP, the peptidase activity of the 26 S proteasome is lost. The Zn2+-induced
      structural and functional changes are fully reversible; removal of Zn2+ is
      followed by reassociation of subunit Rpn10/p54 to the RP, reassembly of the 26 S
      proteasome and resumption of the peptidase activity. After the Zn2+-induced
      dissociation, Rpn10/p54 interacts with a set of non-proteasomal proteins. Hsp82
      (heat-shock protein 82) has been identified by MS as the main Rpn10/p54
      interacting protein, suggesting its role in the reassembly of the 26 S proteasome
      after Zn2+ removal. The physiological relevance of another Rpn10/p54-interacting
      protein, the Smt3 SUMO (small ubiquitin-related modifier-1)-activating enzyme,
      detected by chemical cross-linking, has been confirmed by yeast two-hybrid
      analysis. Besides the Smt3 SUMO-activating enzyme, the Ubc9 SUMO-conjugating
      enzyme also exhibited in vivo interaction with the 5'-half of Rpn10/p54 in yeast
      cells. The mechanism of 26 S proteasome disassembly after ATP depletion is
      clearly different from that induced by Zn2+. Rpn10/p54 is permanently RP-bound
      during the ATP-dependent assembly-disassembly cycle, but during the Zn2+ cycle it
      reversibly shuttles between the RP-bound and free states.

PMID- 15946126
TI  - Progressive familial intrahepatic cholestasis: genetic disorders of biliary
      transporters.
AB  - Progressive familial intrahepatic cholestasis types 1, 2 and 3 are childhood
      diseases of the liver. Benign recurrent intrahepatic cholestasis is predominantly
      an adult form with similar clinical symptoms that spontaneously resolve. These
      genetic disorders have significantly helped to unravel the basic mechanisms of
      the canalicular bile transport processes. Progressive familial intrahepatic
      cholestasis type 1 involves a gene also linked to benign recurrent intrahepatic
      cholestasis. The gene codes for an aminophospholipid translocase protein that
      maintains the integrity of the membrane. How a mutation in this protein causes
      cholestasis is unknown but is thought to involve the enterohepatic recirculation
      of bile acids. Progressive familial intrahepatic cholestasis types 2 and 3
      involve the canalicular bile salt export pump and a phospholipid translocase,
      respectively, both of which are fundamental to bile secretion. This review covers
      the clinical manifestations, genetics, treatment and mechanism of each disease.

PMID- 15946127
TI  - Gastrointestinal stromal tumors: clinical profile, pathogenesis, treatment
      strategies and prognosis.
AB  - Abstract Gastrointestinal stromal tumors (GIST), although the most common
      mesenchymal neoplasms of the gastrointestinal (GI) tract, account for <1% of all
      GI malignancies. Up to 94% of these tumors express the CD117 antigen. Most
      patients present in the fifth to seventh decade, the commonest symptom being that
      of an abdominal mass. Surgery is the main modality of therapy, but even after
      adequate resection the vast majority of GIST reoccur, and in approximately 50%
      the liver is the main site of the metastasis. Long-term, maybe even lifelong
      follow up of these patients after initial resection cannot be over-emphasized.
      Initial tumor size and mitotic rate are the most useful parameters to predict
      malignant potential. In view of high postoperative recurrence, adjuvant forms of
      therapy are being explored, and the tyrosine kinase inhibitor imatinib holds the
      most promise.

PMID- 15946128
TI  - Comprehensive clinical assessment improves the accuracy of predicting cirrhosis
      in chronic hepatitis C.
AB  - BACKGROUND: The diagnosis of cirrhosis in chronic hepatitis C (CHC) is important
      but difficult in those who are unable to undergo liver biopsy. Thus, the aims of
      the present study were to compare separately and in combination, clinical markers
      of liver disease, the discriminant score (DS) and serum hyaluronic acid (HA) for
      their ability to predict cirrhosis in CHC. METHODS: Two groups of consecutive
      patients (groups 1 and 2) with CHC were analyzed. Clinical data and routine
      laboratory results at the time of liver biopsy were collected, and serum HA
      levels were assayed. A clinical examination score (CES) was constructed using the
      sum of clinical markers of liver disease in group 1 and was validated in group 2,
      the DS was calculated, and a serum HA score (HAS) was produced. Combination
      scores were constructed using the sum of the CES, DS and HAS. Histological
      analysis of liver biopsies was performed by hepatopathologists blinded to
      clinical results. RESULTS: One hundred and fifty-one patients with CHC (group 1,
      n = 47; group 2, n = 104) including 27 with cirrhosis were assessed. Serum HA was
      more accurate than either CES or DS in the prediction of cirrhosis. The
      combination of CES, DS and HAS enabled the most accurate prediction of cirrhosis
      with a sensitivity and specificity of 78% and 93%, and a positive predictive
      value and negative predictive value of 75% and 94%, respectively. CONCLUSIONS: A
      comprehensive clinical assessment utilizing clinical and laboratory data more
      accurately predicts the presence and absence of cirrhosis in CHC than individual
      markers.

PMID- 15946129
TI  - Chronic hepatitis B virus infection in the Asia-Pacific region and Africa: review
      of disease progression.
AB  - Countries in the the Asia-Pacific region and Africa tend to have the highest
      prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses
      from an asymptomatic persistently infected status to chronic hepatitis B,
      cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim
      of this review was to summarize rates and risk factors for progression between
      disease states in the Asia-Pacific region and Africa. A literature search was
      conducted employing MEDLINE and EMBASE (1975-2003) using the following key words:
      hepatitis B, natural history, disease progression, cirrhosis, hepatocellular
      carcinoma, mortality, Africa and the Asia-Pacific region. Bibliographies of
      articles reviewed were also searched. Ranges for annual progression rates were:
      (i) asymptomatic persistent infection to chronic hepatitis B, 0.84-2.7%; (ii)
      chronic hepatitis B to cirrhosis, 1.0-2.4%; and (iii) cirrhosis to hepatocellular
      carcinoma, 3.0-6.6%. Patients with asymptomatic persistent infection and chronic
      hepatitis B had relatively low 5-year mortality rates (<4%); rates (>50%) were
      much higher in patients with decompensated liver disease and hepatocellular
      carcinoma. No data were found for progression rates in African populations.
      Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging
      hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk
      factors for hepatocellular carcinoma included cirrhosis, co-infection with
      hepatitis C virus, and genetic and environmental factors. In this review, wide
      ranges of disease progression estimates are documented, emphasizing the need for
      further studies, particularly in Africa, where progression rates are largely not
      available. Summarizing information on factors associated with disease progression
      should assist in focusing efforts to arrest the disease process in those at most
      risk.

PMID- 15946130
TI  - Precore stop codon mutation of hepatitis B virus is associated with low
      breakthrough rate following long-term lamivudine therapy.
AB  - BACKGROUND: Frequent viral breakthroughs limit the usefulness of lamivudine in
      the treatment of chronic hepatitis B (CHB). The purpose of the present study was
      to evaluate the effects of precore stop codon mutation (G to A mutation at
      nucleotide 1896; A(1896)) of hepatitis B virus (HBV) on the occurrence of viral
      breakthrough following lamivudine therapy. METHODS: Among 260 consecutive CHB
      patients treated with lamivudine for >12 months, 231 patients whose pretreatment
      sera were available were tested for A(1896) variant of HBV using direct
      sequencing. RESULTS: Between patients with A(1896) variant (n = 74) and those
      without it (n = 157), there was no difference in age, gender, serum alanine
      aminotransferase (ALT) level, the duration of therapy and prevalence of core
      promoter mutants. Serum hepatitis B e antigen (HBeAg) positivity and HBV-DNA
      level were lower (P = 0.00 and P = 0.01) and liver cirrhosis was more commonly
      associated in patients with A(1896) variant mutant compared with those without
      it. In univariate analysis, viral breakthrough was more frequent in HBeAg
      positive patients (P = 0.03) and in those with high serum HBV-DNA level (P =
      0.01) as well as in those without A(1896) variant (P = 0.01). However, in
      multivariate analysis, the absence of A(1896) variant (P = 0.02) and high serum
      HBV-DNA level (P = 0.03) were independent factors for viral breakthrough
      following lamivudine therapy. The cumulative viral breakthrough rates at 1 and 2
      years were much lower in patients with A(1896) variant compared with those
      without it (P = 0.01). CONCLUSION: The stop codon mutation at the precore region
      of HBV in addition to low serum HBV-DNA level may be associated with low
      breakthrough rate following lamivudine therapy.

PMID- 15946131
TI  - Possible contribution of prior hepatitis B virus infection to the development of
      hepatocellular carcinoma.
AB  - BACKGROUND: The prevalence of prior hepatitis B virus (HBV) infection in
      hepatocellular carcinoma (HCC) patients and its role in hepatocarcinogenesis are
      not clear. The aim of the present study is to clarify the importance of prior HBV
      infection in development of HCC. METHODS: Of 1288 consecutive HCC patients
      between January 1999 and October 2002, 1008 patients were enrolled. To determine
      the influence of prior HBV infection in hepatitis B surface antigen (HBsAg)
      negative HCC, the prevalence of antibody to hepatitis B core antigen (anti-HBc)
      was examined according to age, and the clinical features were compared between
      the anti-HBc positive and the negative groups. RESULTS: The proportion of HBsAg
      negative HCC patients, HCC patients with antibody to hepatitis C virus (anti-HCV;
      C-HCC) and HCC patients negative for both HBsAg and anti-HCV (nBnC-HCC),
      increased with age. The anti-HBc-positive rates in C-HCC patients also increased
      with age. Those rates in nBnC-HCC patients were >50% in all age groups.
      Furthermore, it was found that the anti-HBc-positive rates of these patients were
      higher than those of corresponding control patients. Tumor size and a positive
      rate for vessel involvement both in C-HCC and nBnC-HCC patients were larger and
      higher, respectively, in anti-HBc-positive patients compared with anti-HBc
      negative patients, although the difference in nBnC-HCC did not reach statistical
      significance because of the small numbers. These tumor characteristics were
      similar to those of B-HCC patients. CONCLUSION: A possible contribution of prior
      HBV infection to the development of HCC is indicated.

PMID- 15946132
TI  - Effects of growth factors on the growth and differentiation of mouse fetal liver
      epithelial cells in primary cultures.
AB  - BACKGROUND AND AIMS: Growth factors (GF) are thought to affect the growth and
      differentiation of hepatocytes during liver development. However, in the midfetal
      liver, little is known concerning the role of GF. METHODS: The DNA synthesis of
      fetal liver epithelial cells (FLEC) in monolayer culture and the liver-specific
      gene expressions of FLEC in 3-D culture were examined in medium supplemented with
      various GF. RESULTS: DNA synthesis of FLEC was higher than that of adult
      hepatocytes without GF, and was increased by hepatocyte growth factor (HGF),
      heparin-binding epidermal growth factor-like growth factor (HB-EGF), basic
      fibroblast growth factor (bFGF), epidermal growth factor (EGF) or transforming
      growth factor-alpha (TGF-alpha). However, FLEC responded less to GF in terms of
      DNA synthesis than adult hepatocytes. The liver-specific gene expressions were
      increased in the presence of HGF, HB-EGF, bFGF and EGF. In embryonic day (E) 13.5
      FLEC, this increase was more apparent in the presence of HB-EGF, whereas in E14.5
      FLEC, it was more apparent in the presence of HGF. CONCLUSIONS: Hepatocyte growth
      factor, HB-EGF, bFGF, EGF and TGF-alpha increased DNA synthesis of FLEC. HGF, HB
      EGF, bFGF and EGF led to an increase in liver-specific gene expressions; and
      their effects on differentiation differ as a function of gestation age.

PMID- 15946133
TI  - Expression of cytochrome P450 enzymes in hepatic organoid reconstructed by rat
      small hepatocytes.
AB  - BACKGROUND AND AIMS: Small hepatocytes (SH), which are hepatic progenitor cells,
      were isolated from an adult rat liver. SH in a colony sometimes change their
      shape from small to large and from flat to rising/piled-up. The morphological
      changes of SH may be correlated with hepatic maturation. Cytochrome P450s (CYP)
      are drug-metabolizing enzymes and the expression is one of hepatic differentiated
      functions. However, it is well known that the re-expression and maintenance of
      CYP activity are very difficult in cultured hepatocytes. We investigated the
      expression of CYP and the enzymatic activities in long-term cultured SH. METHODS:
      SH were isolated from adult rat livers and SH colonies were collected, replated
      on new dishes, and then cultured. CYP1A1/2, CYP2B1, CYP3A2, CYP4A1, and CYP2E1
      were induced by the addition of 3-methylcholanthrene, phenobarbital, pregnenolone
      16alpha-carbonitrile, clofibric acid, and ethanol, respectively.
      Immunocytochemistry, immunoblots, and enzyme activities were examined. RESULTS:
      SH could differentiate into mature hepatocytes by the addition of Matrigel and re
      express constitutive CYPs. The expression of CYP1A1/2, CYP2B1, CYP3A2, and CYP4A1
      dose-dependently increased and the amounts gradually increased with time in
      culture, especially in the cells treated with Matrigel. Activities of CYP1A,
      CYP2B, CYP3A and CYP2E in SH treated with Matrigel induced by each of the
      inducers were approximately 120-fold, 2.8-fold, 6.4-fold and 0.8-fold higher than
      in the control. CONCLUSION: The matured SH could re-express the constitutive CYP
      and recover inducibility, not only of protein expression but also of enzyme
      activities.

PMID- 15946134
TI  - Survival in hepatocellular carcinoma: impact of screening and etiology of liver
      disease.
AB  - BACKGROUND AND AIMS: As the merits of screening at-risk populations for
      hepatocellular carcinoma (HCC) remain unclear, we compared the clinico-pathologic
      features and survival of patients with cirrhosis and HCC detected by screening
      (Group A) to that in non-screened cases (Group B). METHODS: We studied cirrhotics
      who developed HCC between 1994 and 2002. During this period, cirrhotics managed
      by the Gastroenterology Unit were regularly screened at 6-12 monthly intervals
      while those managed by other hospital units were not. Demographic data, tumor
      details, treatment received and survival were recorded and compared according to
      screening status. RESULTS: There were 96 cases identified; 41 by screening (group
      A) and 55 by non-screening methods (Group B). HCC in Group A were smaller (P <
      0.01), more likely unilobar (P < 0.01), at an early stage (P < 0.0005) and before
      vascular invasion (P < 0.005) than Group B cases. The frequency of hepatic
      surgery and/or local ablation was higher in Group A than Group B (P = 0.001).
      Overall median survival of Group A was 882 days versus 99 days in Group B (P <
      0.0001). One- and 3-year probabilities of survival in Group A were 89% and 38%,
      versus 33% and 19% in Group B (P < 0.001). Independent predictors of survival
      included screening, Child-Pugh score, creatinine, tumor stage and absence of
      alcohol as the etiology. CONCLUSIONS: Screening for HCC in cirrhosis identifies
      tumors at an earlier stage, results in a higher chance of receiving curative
      treatment and possibly improves patient survival. The absence of alcoholic liver
      disease impacts favorably on survival.

PMID- 15946135
TI  - Recombinant human factor VIIa-induced alterations in tissue factor and
      thrombomodulin in patients with advanced liver cirrhosis.
AB  - BACKGROUND: Recombinant human factor VIIa (rhFVIIa) is used to treat hemophilia
      and occasionally individuals with liver disease. The aim of the present study was
      to investigate the consequences of rhFVIIa in individuals with advanced liver
      disease in an attempt to understand the mechanism of action of rhFVIIa in this
      unique population. METHODS: Levels of plasma tissue factor, plasminogen activator
      inhibitor-1, tissue factor pathway inhibitor, fibrin split products, D-dimers and
      free thrombomodulin were measured following the administration of rhFVIIa in 17
      subjects. The results were compared to normal controls. RESULTS: The prothrombin
      time declined from 20.2 +/- 2.8 s to 14.3 +/- 3.9 s (P < 0.01). No change in the
      activated partial thromboplastin time occurred. A 15.6% reduction in
      thrombomodulin was observed (P < 0.05). A mean 75.2% reduction in plasma tissue
      factor occurred (P < 0.01). Tissue factor pathway inhibitor levels declined to
      less than the control value (P < 0.05). No changes in plasminogen activator
      inhibitor-1, fibrin split products or D-dimer levels occurred. CONCLUSIONS: These
      data demonstrate that rhFVIIa administration to individuals with liver disease
      results in (i) a transient improvement in the prothrombin time; (ii) no change in
      the activated partial thromboplastin time; and (iii) a marked reduction in the
      levels of thrombomodulin and tissue factor. These data suggest that rhFVIIa binds
      tissue factor and enhances tissue factor and thrombomodulin clearance from the
      circulation.

PMID- 15946136
TI  - Gender differences in vascular reactivity of aortas from rats with and without
      portal hypertension.
AB  - BACKGROUND: Inflammatory responses related to portal hypertension may be
      different in male and female rats. Most experimental studies of portal
      hypertension have involved male animals, and little information is available on
      gender differences in this setting. The aim of the present study was to compare
      aortic reactivity in female and male rats with and without portal hypertension.
      METHODS: Contraction response curves to phenylephrine were studied with aortic
      rings, with and without endothelium. For relaxation studies, rings were
      precontracted with phenylephrine 10(-7) mol/L and then exposed to acetylcholine
      10(-4) mol/L. Portal hypertension was provoked by calibrated portal stenosis
      performed 2 weeks before experiments. RESULTS: In non-hypertensive conditions,
      the contractile response to increasing phenylephrine concentrations was
      significantly stronger in rings from male than female rats, both with and without
      endothelium. In male rats with portal hypertension, the phenylephrine
      concentration-response curves were lowered and shifted to the right in aortic
      rings both with and without endothelium. In female rats, portal hypertension did
      not induce significant changes in the phenylephrine concentration-response
      curves. In female rats, portal hypertension induced a marked increase in
      relaxation (157 +/- 123% vs 81 +/- 64% in controls); the increase was also
      stronger than that in male rats with portal hypertension (95 +/- 6%; P < 0.01).
      CONCLUSION: Clear gender differences were observed in vasoconstrictor
      responsiveness of aortic rings from rats with and without portal hypertension.
      Contrary that in male rats, portal hypertension did not induce vascular
      hyporesponsiveness in female rats. Further investigations are required to explain
      these differences.

PMID- 15946137
TI  - Camostat, an oral trypsin inhibitor, reduces pancreatic fibrosis induced by
      repeated administration of a superoxide dismutase inhibitor in rats.
AB  - BACKGROUND AND AIM: An oral trypsin inhibitor, camostat (CM), has a beneficial
      effect on chronic pancreatitis, but its mechanism is not yet fully understood.
      Recently, pancreatic stellate cells (PSC) have been reported to play an essential
      role in pancreatic fibrosis. An experimental model of pancreatic fibrosis induced
      by a superoxide dismutase (SOD) inhibitor (diethyldithiocarbamate [DDC]) was
      developed in rats. Thus, the effect of an oral trypsin inhibitor on pancreatic
      fibrosis and PSC was investigated. METHODS: Pancreatic fibrosis was induced in
      rats using DDC (DDC rats). DDC + CM rats were administered DDC, and subsequently
      were fed a diet containing CM. Immunohistochemistry of the pancreas was performed
      with monoclonal anti-alpha-smooth muscle actin (alpha-SMA) antibody and anti
      desmin antibody. RESULTS: The DDC rats showed a significant increase in alpha-SMA
      positive cells or desmin-positive cells compared with control rats. These
      significant increases in the fibrotic area improved after treatment with CM. The
      level of prolyl hydroxylase in the pancreas, which significantly increased as a
      result of DDC, decreased after treatment with CM. CONCLUSION: Camostat has a
      beneficial effect on pancreatic fibrosis induced by the administration of a SOD
      inhibitor, which inhibits the proliferation and activation of PSC.

PMID- 15946138
TI  - Outcome of colorectal carcinoma in patients under 40 years of age.
AB  - AIMS: Colorectal carcinoma in patients under 40 years of age usually has a poor
      prognosis. Controversies still exist regarding the features and the prognosis of
      colorectal cancer in young patients. METHODS: The records of 45 patients with
      histologically confirmed colorectal carcinoma treated between 1992 and 2002 at
      the Division of Oncology at Taipei Veterans General Hospital were reviewed. The
      relevance of sex, duration of symptoms, tumor site, histological type, lymph node
      involvement, Karnofsky performance status (KPS), carcinoembryonic antigen (CEA)
      and lactate dehydrogenase (LDH) levels at the diagnosis and tumor stage to
      overall survival (OS) were determined by univariate analysis, and their
      independent significance were tested by multivariate analysis. RESULTS: Most
      patients presented with an advanced tumor stage (24% Dukes' C and 66% Dukes' D).
      Colon carcinoma constituted 76% of the colorectal tumors. Family history was
      present in two patients and did not affect the OS. Two patients were found to
      have colon carcinoma during pregnancy. The 5-year survival rate in patients with
      Stage B, C, and D were 25, 16 and 0%, respectively. With aggressive treatment,
      patients with early stage carcinoma achieved longer survival. Eleven patients
      received resection of metastatic carcinoma of the liver, lung and ovary. Adjuvant
      chemotherapy with irinotecan/5-fluorouracil-based chemotherapy seemed to improve
      the OS in such patients, though the OS was still poorer than in patients with
      early stage tumors. In univariate analysis, KPS (P = 0.0001), lymph node
      involvement (P = 0.0024), CEA (P = 0.0423) and LDH levels (P = 0.0126) at the
      diagnosis and tumor stage (P = 0.0122) proved to be significant predictors of
      overall survival. Multivariate analyses revealed that KPS > or =70% (P = 0.007)
      and normal LDH levels at diagnosis (P = 0.004) were predictive of overall
      survival in this population. CONCLUSIONS: The present study shows that
      performance status and preoperative LDH levels were the major determinants for
      survival in patients with colorectal carcinoma under 40 years of age and the
      present series also suggests that surgical resection of metastatic colorectal
      carcinoma followed by adjuvant chemotherapy might be beneficial in certain
      patients. The data also suggests that current treatment modalities for young
      patients with advanced colorectal cancer might not be effective and more
      effective therapeutic regimens might be needed. Thus, it is important for
      surgeons to recognize the potential for colorectal cancer in young patients and
      to take an aggressive approach to the diagnosis and early treatment of the
      disease.

PMID- 15946139
TI  - Clinical review of tuberculous peritonitis in 39 patients in Diyarbakir, Turkey.
AB  - Abdominal tuberculosis (TB) is a rare manifestation, which can be overlooked on
      long-lasting and non-specific findings unless a high index of suspicion is
      maintained. The purpose of the present study was to investigate the diagnostic
      features of 39 patients hospitalized with tuberculous peritonitis (TBP) in Dicle
      University Hospital, Turkey between January 1994 and August 2003. Twenty-two
      patients were male; patient age ranged between 1 and 59 years (mean: 16.2 +/-
      14.4 years). There were 21 patients (54%) under 15 years of age. Thirteen
      children had a history of familial TB and seven adults had prior history of TB.
      Six (29%) of 21 pediatric cases had bacille Calmette-Guerin (BCG) scars and
      results of 5-tuberculin units (TU) tuberculin test were positive in seven
      children (18%). Of all cases, the most common presenting findings were abdominal
      pain (95%), ascites (92%) and abdominal distention (82%). Five of the patients
      had accompanying pulmonary TB, and six patients (15%) had intestinal TB who were
      admitted to emergency service with acute abdomen, of whom three (8%) had
      perforation and three (8%) had ileus. Histopathologically 20 cases (51%) were
      proven on abdominal ultrasonography, and computed tomography revealed most
      commonly ascites and thickening of peritoneum. No microbiologic evidence was
      obtained except three positive culture results for Mycobacterium tuberculosis. As
      a result, TBP should be considered for diagnosis, in patients with non-specific
      symptoms of abdominal pain, wasting, fever, loss of appetite, abdominal
      distension and even symptoms of acute abdomen, because early diagnosis and
      effective treatment will decrease morbidity and mortality.

PMID- 15946140
TI  - Gastrobiliary motility is not coordinated in patients with non-ulcer dyspepsia of
      normal gastric emptying time: simultaneous sonographic study.
AB  - BACKGROUND: Disorders of the motor function of the upper gastrointestinal tract
      have been implicated in the pathogenesis of non-ulcer dyspepsia. Approximately
      50% of patients with abdominal symptoms (without ulcer) have normal gastric
      emptying. Apart from gastric emptying, other mechanisms are very important in the
      etiology of non-ulcer dyspepsia. METHODS: Gastric emptying and gallbladder
      motility were simultaneously investigated in 16 patients with non-ulcer dyspepsia
      and in 15 healthy controls. Fasting blood samples were taken, and pepsinogen
      levels were assayed. RESULTS: Gastric emptying time, fasting antral diameter, and
      post-prandial antral diameter were not significantly different between the
      patients with non-ulcer dyspepsia and the controls. Fasting gallbladder volume,
      the time required to reach minimal gallbladder residual volume, minimal
      gallbladder residual volume, and the serum levels of pepsinogen were not
      significantly different. Simple linear regression was used to summarize the
      relationship between gastric emptying time and time required to reach minimal
      gallbladder residual volume. In the controls, the gastric emptying time and time
      required to reach minimal gallbladder residual volume were linearly related.
      However, in the patients with non-ulcer dyspepsia, they were not related.
      CONCLUSIONS: These observations suggest that disturbance of coordination between
      gastric emptying and gallbladder emptying is a cause of the symptoms of non-ulcer
      dyspepsia.

PMID- 15946141
TI  - Pancreatic tumor associated with pancreas divisum.
AB  - BACKGROUND: Although there has been considerable controversy regarding pancreas
      divisum and pancreatitis, little discussion of this has taken place. The purpose
      of the present paper was to investigate the relationship between these two
      conditions. METHODS: A retrospective investigation was undertaken of pancreatic
      tumors associated with pancreas divisum, in 650 cases of pancreatic carcinoma, 80
      cases of intraductal papillary mucinous tumor of the pancreas and 32 cases of
      pancreas divisum. RESULTS: Of these 32 cases, four (12.5%) were associated with
      pancreatic tumor: pancreatic carcinoma (n = 3) and intraductal papillary mucinous
      tumor (n = 1). All tumors developed from the dorsal pancreas of pancreas divisum.
      Periductal and interlobular fibrosis detected in the non-carcinomatous pancreas
      of the margin of distal pancreatectomy implied that chronic dorsal pancreatitis
      associated with pancreas divisum preceded carcinoma. CONCLUSIONS: Pancreatic
      tumors were detected in 12.5% of cases of pancreas divisum. In pancreas divisum,
      longstanding pancreatic duct obstruction caused by relative stenosis of the minor
      duodenal papilla might be a factor promoting oncogenesis.

PMID- 15946142
TI  - Quality of life measures for fecal incontinence and their use in children.
AB  - BACKGROUND: Fecal incontinence is a common problem within society from childhood
      through to the elderly. Its clinical assessment has focussed on severity and
      frequency of soiling episodes but it is increasingly recognized to have an impact
      on physical, psychological and social well-being (quality of life [QOL]). This is
      likely to be particularly important in childhood. The aim of the present study
      was to critically evaluate the development and application of disease-specific
      QOL measures, focusing particularly on their use in children. METHODS: Generally
      recognized disease-specific QOL measures for fecal incontinence were identified
      and their generation and validation were critically evaluated. RESULTS: Six
      instruments were identified: Ditesheim and Templeton QOL Scoring System,
      Manchester Health Questionnaire, Hirschsprung's Disease/Anorectal Malformation
      Quality of Life Questionnaire (HAQL), Gastrointestinal Quality of Life Index
      (GIQLI), Fecal Incontinence TyPE Specification, and the Fecal Incontinence
      Quality of Life Scale (FIQL). Although the FIQL appeared to be the better tool
      for adults with fecal incontinence because it was brief and had the best validity
      and reliability, it needed further modification to become appropriate for use in
      children. In particular, items relating to sexual activity were inappropriate.
      CONCLUSION: Neither the FIQL nor other disease-specific instruments met basic
      psychometric standards for use in children with fecal incontinence. Substantial
      revision of currently available instruments will be required to meet the needs of
      this population.

PMID- 15946143
TI  - Cytokeratin immunoreactivity patterns in short-segment Barrett's esophagus in
      Japanese patients.
AB  - BACKGROUND: The origin of intestinal metaplasia at the esophagogastric junction
      has clinical importance. However, it can be difficult to differentiate between
      intestinal metaplasia of short-segment Barrett's esophagus and cardiac intestinal
      metaplasia due to Helicobacter pylori infection. Specific patterns of cytokeratin
      (CK)7 and CK20 have been detected in long-segment Barrett's esophagus. The aim of
      the present study was to assess the immunostaining patterns associated with short
      segment Barrett's esophagus. AIMS: Paraffin-embedded biopsy specimens were
      prepared from 128 patients with intestinal metaplasia of long-segment Barrett's
      esophagus (n = 3), short-segment Barrett's esophagus without H. pylori infection
      (n = 22), short-segment Barrett's esophagus with H. pylori infection (n = 22),
      and cardiac mucosa (n = 49) and gastric mucosa from antrum and fundus (n = 44)
      with H. pylori infection. Sections were prepared and immunostained for CK7 and
      CK20. RESULT: A Barrett's CK7/20 pattern was present in all three patients (100%)
      with long-segment Barrett's esophagus, 21 of 22 patients (95%) with short-segment
      Barrett's esophagus without H. pylori infection, and six of 22 patients (27%)
      with short-segment Barrett's esophagus with H. pylori infection (P < 0.05).
      CONCLUSION: Intestinal metaplasia of short-segment Barrett's esophagus in
      patients without H. pylori infection is thought to be similar to that seen in
      long-segment Barrett's esophagus.

PMID- 15946144
TI  - Low-dose rabeprazole, amoxicillin and metronidazole triple therapy for the
      treatment of Helicobacter pylori infection in Chinese patients.
AB  - BACKGROUND: Rabeprazole in combination with amoxicillin and metronidazole (RAM)
      has been shown to be an effective second-line treatment of Helicobacter pylori
      infection. The effects were compared of 7-day low-dose and high dose rabeprazole
      in RAM for the primary treatment of H. pylori infection in Chinese patients.
      METHODS: Helicobacter pylori-positive dyspeptic patients were randomized to
      receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400
      mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and
      metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter
      pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping
      medications. side-effects of treatments were documented. RESULTS: A total of 120
      patients were eligible for analysis. By intention-to-treat and per-protocol
      analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and
      76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were
      well-tolerated and compliance was >98% in both groups. CONCLUSIONS: Low-dose
      rabeprazole in combination with amoxicillin and metronidazole is an effective,
      economical and well-tolerated therapy for the treatment of H. pylori infection in
      Chinese population.

PMID- 15946145
TI  - Eradication of Helicobacter pylori reduced the immunohistochemical detection of
      p53 and MDM2 in gastric mucosa.
AB  - BACKGROUND: Although Helicobacter pylori has been regarded as a pathogen of
      gastric cancer, the mechanism by which H. pylori is involved in gastric
      carcinogenesis remains unknown. To clarify the role of H. pylori in
      carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple
      double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori
      eradication. METHODS: Biopsy specimens were obtained from 31 patients with H.
      pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after
      successful eradication. In addition, biopsy specimens from 12 patients with non
      infected gastric mucosa were obtained. Immunohistochemical analysis was performed
      on the specimens using primary antibodies specific for p53 and MDM2. RESULTS: Six
      months after H. pylori eradication, labeling indices for p53 were significantly
      reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum
      (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly
      reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P <
      0.01). In the non-infected group, labeling indices for p53 and MDM2 in the
      gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori
      infected group. CONCLUSION: A significant increase is shown in p53 and MDM2
      expression in H. pylori-infected gastric mucosa as compared to normal gastric
      mucosa; but successful eradication of H. pylori dramatically reduced the p53 and
      MDM2 levels. Therefore, H. pylori infection may be associated with alteration of
      cell proliferation and apoptosis.

PMID- 15946146
TI  - Pre-cutting using a noseless papillotome with independent lumens for contrast
      material and guidewire.
AB  - BACKGROUND: The technical success of therapeutic endoscopic retrograde
      cholangiopancreatography (ERCP) depends on selective cannulation into the bile
      duct. We have developed a new type of precut papillotome for selective
      cannulation. METHODS: The newly developed precut papillotome has been equipped
      not only with a lumen for contrast materials but also with an independent lumen
      for the guidewire. The operation of the guidewire and the injection of contrast
      material can be carried out simultaneously. The precut papillotome has a 20-mm
      long knife and no leading tip. Half the proximal side of the knife is coated for
      insulation. RESULTS: Selective biliary cannulation failed in 26 of 293 patients
      (8.9%) in whom therapeutic ERCP was attempted. We applied the precut papillotome
      to these 26 patients and selective cannulation was successful in 24 of 26
      patients (success rate: 92.3%). No major complications occurred, although mild
      bleeding, which did not require endoscopic hemostasis or blood transfusion, was
      observed only in one patient. CONCLUSIONS: Although further studies with a large
      number of patients are needed to evaluate the efficacy of the papillotome, this
      papillotome may contribute to increase the safety and the success rate of
      precutting.

PMID- 15946147
TI  - Images of interest. Gastrointestinal: aortoduodenal fistulae.

PMID- 15946148
TI  - Images of interest. Gastrointestinal: sclerosing encapsulating peritonitis.

PMID- 15946149
TI  - Images of interest. Hepatobiliary and pancreatic: pseudotumor of the liver.

PMID- 15946150
TI  - Images of interest. Hepatobiliary and pancreatic: suture material and bile duct
      stones.

PMID- 15946151
TI  - Azathioprine, 6-mercaptopurine and thiopurine S-methyltransferase.

PMID- 15946152
TI  - Liver transplantation in a child with celiac disease.
AB  - Recently, an atypical form of celiac disease (CD) has been identified, in which
      gastrointestinal symptoms are less pronounced. Other organs can be more or less
      severely affected, and the disease might be unrecognized and undiagnosed. In some
      cases, hypertransaminasemia has been indicated as the first symptom of CD in
      infancy. A direct relationship between liver damage and glutensensitivity has
      been proven by the disappearance of biochemical signs and histological lesions of
      the liver after the initiation of the gluten-free diet. The present case report
      is of a 14-year-old girl affected by CD and severe hepatic failure who underwent
      a liver transplant. To our knowledge, this case is the first report of liver
      involvement related to CD which is so severe as to require a liver transplant in
      a child. Because most patients with CD remain undiagnosed, and, as observed in
      the present report, untreated CD with subclinical hepatic involvement can lead to
      more serious liver disease, a more aggressive diagnostic work-up for CD in the
      general population is warranted.

PMID- 15946153
TI  - Solitary polypoidal rectal ganglioneuroma: a rare presentation of a rare tumor.

PMID- 15946154
TI  - Impact of tumor factors on the prognosis of patients with advanced cirrhosis
      (Child-Pugh class C) and hepatocellular carcinoma.

PMID- 15946155
TI  - Colonoscopic diagnosis of whipworm infection.

PMID- 15946156
TI  - Synchronously resected double primary hepatic cancer, hepatocellular carcinoma
      and cholangiocarcinoma.

PMID- 15946157
TI  - Direct cytopathic liver injury and acute respiratory distress syndrome associated
      with gilliam-type tsutsugamushi disease.

PMID- 15946158
TI  - Central GABAA but not GABAB receptors mediate suppressive effects of caudal
      hindbrain glucoprivation on the luteinizing hormone surge in steroid-primed,
      ovariectomized female rats.
AB  - The neurochemical mechanisms that link caudal hindbrain glucoprivic-'sensitive'
      neurones with the forebrain gonadotrophin-releasing hormone (GnRH)-pituitary
      luteinizing hormone (LH) axis remain unclear. Available studies indicate that the
      amino acid neurotransmitter, gamma-aminobutyric acid (GABA), inhibits
      reproductive neuroendocrine function, and that caudal fourth ventricular
      administration of the glucose antimetabolite, 5-thioglucose (5TG), enhances GABA
      turnover within discrete septopreoptic structures that regulate LH secretion. The
      current experiments utilized the selective GABA(A) and GABA(B) receptor
      antagonists, bicuculline and phaclofen, as pharmacological tools to investigate
      whether one or both receptor subtypes function within neural pathways that
      suppress GnRH neuronal transcriptional activation and LH release during central
      glucose deficiency. During the ascending phase of the afternoon LH surge, groups
      of steroid-primed, ovariectomized female Sprague-Dawley rats were pretreated by
      lateral ventricular administration of bicuculline, phaclofen, or vehicle only,
      before fourth ventricular injection of 5TG or vehicle. The data indicate that, 2
      h after 5TG treatment, Fos immunoexpression by rostral preoptic GnRH neurones and
      plasma LH levels were diminished relative to the vehicle-treated controls, and
      that inhibitory effects of 5TG on these parameters were attenuated by
      pretreatment with bicuculline, but not phaclofen. These results demonstrate that
      central GABA(A), but not GABA(B) receptor stimulation during hindbrain
      glucoprivation, is required for maximal inhibition of reproductive neuroendocrine
      function by this metabolic challenge. The current studies thus reinforce the view
      that central GABAergic neurotransmission mediates regulatory effects of central
      glucoprivic signalling on the GnRH-pituitary LH axis.

PMID- 15946159
TI  - Expression of GABAB receptors in magnocellular neurosecretory cells of male,
      virgin female and lactating rats.
AB  - GABA is one of the key neurotransmitters that regulate the firing activity of
      neurones in the supraoptic (SON) and paraventricular (PVN) nuclei. In the present
      study, we used immunohistochemical techniques to study the distribution and
      subcellular localisation of metabotropic GABA(B) receptors in magnocellular
      neurones in the SON and PVN. Robust GABA(B) receptor immunoreactivity (GABA(B)R;
      both subunit 1 and subunit 2 of the heterodimer), was observed in the SON and
      PVN. At the light microcope level, GABA(B)R immonoreactivity displayed a
      clustered pattern localised both intracytoplasmically and at the plasma membrane.
      Densitometry analysis indicated that GABA(B)R immunoreactivity was significantly
      more intense in vasopressin cells than in oxytocin cells, both in male, virgin
      female and lactating rats, and was denser in males than in virgin females. Light
      and electron microscope studies indicated that cytoplasmic GABA(B)R was localised
      in various organelles, including the Golgi, early endosomes and lysosomes,
      suggesting the cycling of the receptor within the endocytic and trafficking
      pathways. Some smaller clusters at the level of the cell plasma membrane were
      apposed to glutamic acid decarboxylase 67 immunoreactive boutons, and appeared to
      be colocalised with gephyrin, a constituent protein of the postsynaptic density
      at inhibitory synapses. The presence of GABA(B)R immunoreactivity at synaptic and
      extrasynaptic sites was supported by electron microscopy. These results provide
      anatomical evidence for the expression of postsynaptic GABA(B) receptors in
      magnocellular neurosecretory cells.

PMID- 15946160
TI  - Glucocorticoid enhances the neurotoxic actions of quinolinic acid in the striatum
      in a cell-specific manner.
AB  - This study demonstrates that corticosterone can exacerbate the damaging effects
      of infused quinolinic acid (QA) on the dorsal striatum. Adult adrenalectomised
      male rats were pretreated subcutaneously with graded doses of corticosterone (0,
      0.5, 2, 5, 20 and 40 mg/kg/day) for 2 days and then received a unilateral
      infusion of QA (45 nmol) (under Isoflurane/N2O anaesthesia) into the dorsal
      striatum. A control infusion (vehicle) was made into the striatum on the other
      side. Corticosterone treatment was continued and they were killed 7 days later.
      Plasma corticosterone was measured by radioimmunoassay, and thymus weights were
      used as an integrated measure of glucocorticoid activity. Lesion volumes were
      measured on neuronal nuclei stained sections, dopamine and cyclic AMP-regulated
      phosphoprotein 32 (DARRP-32) was used to assess medium spiny neurone survival,
      NADPH-diaphorase histochemistry to assess medium aspiny neurones and, finally,
      choline acetyltransferase to assess large aspiny neurones. Adrenalectomised rats
      showed smaller lesions than control (sham-operated) rats, suggesting significant
      protection. Increasing doses of corticosterone resulted in larger lesions up to
      an apparent ceiling effect at higher doses; there was no evidence of a U-shaped
      dose-response. There was a differential effect of both QA and corticosterone on
      the cell populations of the striatum. Medium spiny neurones were most vulnerable
      to the effects of QA and to the exacerbating actions of corticosterone. Medium
      aspiny neurones were equally vulnerable to QA but corticosterone had no
      additional effect. Large aspiny neurones were relatively less sensitive to QA and
      there was no additional action of administered corticosterone. These results show
      that corticosterone has a selective neuroendangering action within the striatum,
      but there is no evidence for a protective action of glucocorticoids at lower
      doses.

PMID- 15946161
TI  - Sex differences in the neuroendocrine response to short-term fasting in rhesus
      macaques.
AB  - When energy intake is restricted in mammals, there are neuroendocrine adjustments
      in the secretion of reproductive and metabolic hormones to reallocate energy for
      vital functions. In the present study, we investigated whether there were
      differences in the luteinising hormone (LH), growth hormone (GH) and cortisol
      responses to a 48-h fast in adult gonad-intact male and female rhesus macaques.
      In both male and female macaques, blood glucose levels were significantly lower
      in fasted than in control studies, and levels were higher in males than in
      females. Male rhesus monkeys had significantly lower (P < 0.01) mean serum LH
      levels after a 48-h fast than under fed conditions and this was attributable
      primarily to a decrease in the amount of LH released during each secretory
      episode. In fasted females, serum LH levels were significantly greater (P < 0.05)
      than during the fed conditions but no differences were found in pulse amplitude
      or in the number of pulses. Almost twice as many GH pulses were observed in both
      males and females during fasting but there was no difference in either mean serum
      GH levels or pulse amplitude between control and fasted studies. A typical
      diurnal profile in cortisol levels was observed in both sexes and both
      experimental conditions. Under control conditions, male macaques released less
      cortisol than females, and although fasting increased mean cortisol levels in
      both males and females, only the males shown a significant rise over levels
      observed in control studies. The changes in plasma LH and cortisol levels in
      fasted rhesus macaques are similar to those observed in humans and suggest that
      gonadotrophin and corticotrophin secretion are more resistant to short-term
      energy deprivation in female than in male primates.

PMID- 15946162
TI  - The effect of adrenalectomy on ghrelin secretion and orexigenic action.
AB  - Ghrelin is an orexigenic peptide made both in the periphery and in the central
      nervous system. Relatively little is known about the factors that regulate
      ghrelin secretion. Because both ghrelin and glucocorticoids are increased during
      fasting, we hypothesised that ghrelin secretion from the stomach is stimulated by
      glucocorticoids. Plasma ghrelin concentrations were determined by
      radioimmunoassay in fed and fasted adrenalectomised (ADX) and sham-operated rats.
      Fasting plasma ghrelin concentrations were significantly increased in ADX
      relative to sham rats and were normalised by glucocorticoid replacement. Several
      lines of evidence suggest that the orexigenic action of ghrelin is mediated
      through neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurones. Because ADX
      reduces the orexigenic actions of NPY and AgRP, we hypothesised that ADX would
      also reduce the orexigenic action of ghrelin. Food intake was assessed in ADX and
      sham rats following an intra-third-ventricular injection of either saline or
      ghrelin (1, 5 or 10 microg in 2 microl). ADX rats were equally sensitive to the
      orexigenic action of ghrelin compared to sham rats. Given that ghrelin has been
      shown to stimulate glucocorticoid secretion, the current data imply the existence
      of a regulatory feedback loop whereby glucocorticoids inhibit further ghrelin
      secretion. The results also suggest that, unlike the orexigenic effects of NPY
      and AgRP, the ability of ghrelin to stimulate food intake is maintained in ADX
      rats.

PMID- 15946163
TI  - Intravenous peptide YY3-36 and Y2 receptor antagonism in the rat: effects on
      feeding behaviour.
AB  - Systemic injection of peptide YY3-36 reduces food intake in rodents and humans,
      although some groups have reported a lack of response. PYY3-36 is thought to act
      via the Y2 receptor to presynaptically inhibit the release of neuropeptide Y and
      GABA from hypothalamic arcuate neurones. Due to the controversy surrounding its
      action in rodents, we tested the peptide intravenously on feeding behaviour in
      rats and attempted to block its actions with the Y2 receptor antagonist BIIE0246.
      PYY3-36 significantly decreased food intake during the first hour in male Sprague
      Dawley rats fasted overnight and then re-fed. BIIE0246 had no effect alone on re
      feeding, but completely blocked the action of PYY3-36. In a second experiment of
      similar design, the behavioural satiety sequence (BSS) was studied. Normal rats
      eat, drink, explore and groom before entering rest. PYY3-36 significantly reduced
      food eaten maintaining the normal BSS, although shifting it to the left as
      expected for a natural satiety factor. The latency to rest occurred earlier for
      animals given PYY3-36 alone and PYY3-36 tended to increase the total time in rest
      compared with controls. These behavioural effects of PYY3-36 were blocked by
      BIIE0246, and BIIE0246 alone did not have an effect on the BSS. These results
      support the role of PYY3-36 as a natural satiety factor acting through Y2
      receptors.

PMID- 15946164
TI  - Measuring seasonal time within the circadian system: regulation of the
      suprachiasmatic nuclei by photoperiod.
AB  - Day-length (photoperiod) is the primary environmental signal used to synchronise
      endogenous rhythms of physiology and behaviour. In mammals, the suprachiasmatic
      nuclei (SCN) of the hypothalamus house the master circadian clock. The SCN
      incorporate photoperiodic information and therefore measure both daily and
      seasonal time. Over the past decade, there have been significant advances in the
      understanding of the molecular basis of circadian clocks. It is now becoming
      apparent that the core molecular clock mechanism is itself regulated by
      photoperiod, although there is currently debate as to how this occurs. One recent
      model proposes that distinct groups of core 'clock genes' are associated with
      either morning or evening phases of the daily light/dark cycle. However, the
      validity of associating particular genes to morning and evening has been
      questioned. This article reviews the evidence for photoperiodic regulation of
      circadian clock function and then discusses alternative models that may explain
      the available data.

PMID- 15946165
TI  - Neuroendocrine regulation of prolactin secretion during late pregnancy: easing
      the transition into lactation.
AB  - Prolactin is an anterior pituitary hormone critical for maintaining pregnancy and
      lactation. Under normal conditions, prolactin secretion is tightly regulated by
      inhibitory dopaminergic neuronal systems within the mediobasal hypothalamus in a
      process known as short-loop negative feedback. This review focuses on
      neuroendocrine adaptations to prolactin negative feedback during late pregnancy.
      It is suggested that, in terms of prolactin regulation, late pregnancy is a
      transition period into lactation because many of the neuroendocrine adaptations
      promoting hyperprolactinemia in lactation develop during late pregnancy. As a
      consequence, the maternal brain is geared to provide unrestrained prolactin
      release critical for milk production, maternal care and thus survival of the
      offspring before parturition. The mechanisms responsible for these changes are
      discussed.

PMID- 15946167
TI  - Commentary. The social construction of 'woman's work': nursing labour and status.

PMID- 15946168
TI  - The nurse manager: job satisfaction, the nursing shortage and retention.
AB  - A critical shortage of registered nurses exists in the United States and this
      shortage is expected to worsen. It is predicted that unless this issue is
      resolved, the demand for nursing services will exceed the supply by nearly 30% in
      2020. Extensive analysis of this pending crisis has resulted in numerous
      recommendations to improve both recruitment and retention. The purpose of this
      article is to clearly outline the issues contributing to this problem, and to
      provide the nurse manager with information regarding specific influences on job
      satisfaction as it relates to job turnover and employee retention. To accomplish
      this, an analysis of the literature using both national and international sources
      is used to formulate the lessons learned as well as strategies and future courses
      of action designed to address this shortage.

PMID- 15946169
TI  - Job satisfaction in nursing: validation of a new instrument for the UK.
AB  - AIM: To develop a new, valid and reliable instrument that has been designed and
      evaluated to measure job satisfaction as perceived by nurses with specific
      aspects of contemporary nursing. BACKGROUND: Job satisfaction is a key concept
      within workforce research in nursing and is particularly important within the
      present climate in the UK due to findings linking satisfaction with both quality
      of care and retention of nurses. METHOD(S): Exploratory and confirmatory factor
      analyses were carried out on a large longitudinal dataset from a study of Adult
      branch diploma-qualified nurses in England who completed the scale at three time
      points after qualification. RESULTS: A six-factor solution was supported and
      replicated in a further sample of recently qualified graduate nurses. The
      instrument was also acceptably reliable. CONCLUSION: This new instrument is a
      concise, highly practical and flexible tool, which can be used in a range of
      health care settings and in different measurement contexts.

PMID- 15946170
TI  - Confirming mentorship.
AB  - BACKGROUND: Mentorship is related to nurses' success in nursing practice linked
      to professionalism, nursing quality improvement and self-confidence. AIM: To
      elucidate mentorship of recently registered nurses' view of themselves with
      regard to their development of nursing competencies by means of the Sympathy
      Acceptance-Understanding-Competence (SAUC) model for confirming mentorship.
      METHODS: Questionnaires, personal interviews and focus group interviews were used
      for evaluation 2 years after the completion of a year of mentorship, the subjects
      being eight nurses. FINDINGS: The study showed that novice nurses evaluated their
      mentors as confirming, which is understood as a key factor for novice nurses'
      positively reinforced self-relation (perception of themselves) and self-knowledge
      linked to improved competencies in nursing practice such as more secure and
      motivated to nurse (S-phase), increased capacity to verbalize nursing situations
      (A-phase) and to reflect upon and evaluate patient situations based on patients'
      unique identities as individuals (U-phase), and improved abilities to support
      patients' own resources as individuals from a more holistic view and to establish
      collaboration with other professionals. CONCLUSION: Mentorship enabled novice
      nurses to nurse in a more reflective and holistic way, and their positively
      reinforced self-relation may be understood as a crucial ingredient for
      maintaining quality standards in nursing in the future.

PMID- 15946171
TI  - Job satisfaction in relation to change to all-RN staffing.
AB  - BACKGROUND: A university hospital clinic changed from a mixed to only registered
      nurse staffing, to reduce the staff and to encourage a philosophy of patient
      centred care. The aim was to maintain the same level of service and quality of
      care at a lower cost. AIM: The main purpose of the study was to examine job
      satisfaction in relation to the change from mixed to only registered nurse
      staffing and reduction in number of staff. METHODS: Data were collected by an
      established questionnaire measuring job satisfaction. Non-parametric statistics
      were used to analyse the data. The questionnaire was distributed to 22 nurses on
      the ward on three occasions, covering a period of 3 years. RESULT: The experience
      of having time to plan patient care changed during the investigation period, from
      'sometimes' to 'most often having time'. Nurses with longer work experience gave
      more verbal information to patients and perceived less stress. Information about
      job performance was more important to newcomers on the ward and became less
      important with time. However, quite a few have had regrets over choice of work
      and had considered non-caring work, nevertheless the results show no significant
      changes in overall job satisfaction.

PMID- 15946172
TI  - Why do nurses at a university hospital want to quit their jobs?
AB  - The aim of the study was to investigate to what extent the registered nurses at a
      university hospital intend to quit their present jobs and the reasons for this. A
      total of 833 nurses at a university hospital responded to two mailed, work
      environment questionnaires (Quality Work Competence and Huddinge University
      Hospital Model Questionnaire). About 54% (n = 449) intended to quit and 35% (n =
      155) had already taken steps to do so. Main reasons were dissatisfaction with the
      salary (65%), psychologically strenuous and stressful work (32%), a wish to 'try
      something new' (28%) and limited opportunities to make a professional career
      (19%). Nurses who intended to quit ('quitters') rated a higher work tempo (P <
      0.001), experienced an increased work-related exhaustion (P < 0.001) and a lower
      quality of patient care (P < 0.01). They also perceived to a lower degree that
      their competence was made good use of (P < 0.001) and that they had fewer
      opportunities of developing their own competence (P < 0.001) and making a
      professional career. They were less satisfied with the support from their
      superiors for participating in nursing research and developing projects (P <
      0.001). Finally, the 'quitters' knew to a significantly lesser extent (P < 0.001)
      why they had the actual salary they had, what the salary was based on and what to
      do to improve it. However, it was found that the hospital still had a 'core
      group' of highly motivated and dedicated nurses with an unusually high amount of
      mental energy left. All findings regarding the 'quitters' are factors amenable to
      interventions.

PMID- 15946173
TI  - Factors contributing to the decision to leave nursing care: a study among Swedish
      nursing personnel.
AB  - BACKGROUND: An ageing nursing workforce raises questions of recruitment
      strategies and how to prevent nursing personnel from leaving their jobs. AIM: The
      aim of this study was to examine factors contributing to the decision to leave
      nursing care with special reference to work conditions related to nursing care.
      METHODS: This paper is based on data from a survey of nursing personnel who were
      employed at various county hospitals in Sweden from 1992 to 1995 (n = 1507). A
      self-administered questionnaire was used to identify those who had left nursing
      care voluntarily (n = 158) and to examine factors contributing to their decision
      to leave. RESULTS: Results showed that unsatisfactory salary contributed most to
      the nursing personnel's decision to leave, followed by lack of professional
      opportunities and restricted professional autonomy. CONCLUSION: The fact that
      nursing personnel leave because of unsatisfactory salary and lack of professional
      opportunities underpins the importance of making nursing more attractive in terms
      of financial and professional development. However, the sample size of this study
      was relatively small and larger studies are thus required to further investigate
      the importance of these factors in the decision to leave nursing care.

PMID- 15946174
TI  - Improving first-destination recruitment: nursing students' perceptions of three
      initiatives in London, England.
AB  - BACKGROUND: In the face of recruitment problems, managers are becoming
      increasingly proactive by introducing novel initiatives designed to encourage
      newly qualified nurses to apply to their institutions and catchment areas for
      employment. AIMS AND METHODS: Based on a multimethod survey of students from two
      British universities, this paper explores their perceptions of three very
      different initiatives, each at different stages of development and
      implementation. The 'Home Trust' initiative, provided the majority of clinical
      placements in one hospital. It was experienced by almost all the students who
      reported on it in questionnaires (n = 650), focus groups (n = 7) and interviews
      (n = 30). The 'On Secondment' initiative, seconded Health Care Assistants from
      their jobs into nurse education. It was experienced by a small number of students
      who reported on it in questionnaires (n = 32) and focus groups (n = 3). The
      'Recruitment Clearing House' initiative planned to provide one interview for a
      range of hospitals and job vacancies in a large geographical catchment area. At
      the time of data collection, it was in a conceptual phase and was commented on in
      a small number of focus groups with students (n = 3). In addition, this
      initiative was commented on by recruitment managers in interviews (n = 3).
      RESULTS: Students held strong views on the positive and negative features of both
      current and prospective initiatives. Unique consumer insights were gained,
      particularly into their finer details and consequences. CONCLUSION: Student
      experiences and perceptions are valuable in the planning, implementation and
      review stages of local recruitment initiatives.

PMID- 15946175
TI  - Exploring nursing skill mix: a review.
AB  - AIMS: The overall aims of the paper are to provide an overview of the subject,
      illustrate the need for further research and to raise awareness of the ongoing
      limitations of existing knowledge and present these to those involved in skill
      mix decision making. BACKGROUND: Over the last 20 years health care organizations
      across the globe have seen an increase in the pace of change. The continuing
      drive towards cost-effectiveness, quality of care and the clinical governance
      agenda are causing more and more managers to examine closely the mix of staff
      skills. This paper demonstrates that, despite 20 years of research and skill mix
      management in practice, there continues to be a tension between the use of
      qualified and unqualified staff, particularly, the cost and quality dimensions.
      CONCLUSION: The evidence which currently exists offers some limited support for
      the suggestion that redistribution of certain tasks in nursing could be possible
      and could contribute to strategies for meeting the demands of changes within
      health care delivery. Any reallocation of task, and substitution of qualified by
      unqualified staff, should be based on sound evidence and not merely on staff
      availability, service demand or apparent costs.

PMID- 15946176
TI  - Nurse requirement planning: a computer-based model.
AB  - RATIONALE: The paper considers the recent debate on mandating patient-nurse
      ratios in inpatient units of hospitals, and highlights the need for a
      comprehensive approach to requirement estimation, which can facilitate the
      implementation of mandated patient-nurse ratios in hospitals. AIM: After
      considering the available methods for nurse requirement planning, this paper
      intends to discuss an alternative approach for estimating nurse requirement when
      certain patient-nurse ratios have been prescribed. METHODS: Once the required
      information becomes available, the next task is to estimate unit-wise and overall
      nurse requirement. As the computational effort is quite considerable, the paper
      develops and elucidates a computer-assisted nurse requirement-planning model,
      which helps in systematizing and accelerating the estimation process. RESULTS:
      The computer-based nurse requirement-planning model enables planners to respond
      objectively and promptly to requests for more nurses by nursing administrators
      (who perceive nurse shortages). CONCLUSIONS: The paper demonstrates the unique
      advantage of this computer-based approach over conventional methods, especially
      when the planner wishes to pre-evaluate alternative decision options by
      simulating manpower implications under alternative scenarios.

PMID- 15946178
TI  - Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder.
AB  - Oral submucous fibrosis (OSF) is a chronic debilitating disease and a
      premalignant condition of the oral cavity. It is characterized by a generalized
      submucosal fibrosis. The pathogenesis of the disease is not well established.
      Epidemiological evidences strongly indicate the association of the betel quid
      (BQ) habit and OSF. Various findings indicate the disease to be a consequence of
      disturbances in the homeostatic equilibrium between synthesis and degradation of
      extracellular matrix (ECM), wherein collagen forms a major component, thus can be
      considered as a collagen-metabolic disorder. Transforming growth factor-beta (TGF
      beta) is a potent stimulator of production and deposition of the ECM. The
      objectives of this review are to highlight the molecular events involved in the
      overproduction of insoluble collagen and decreased degradation of collagen
      occurring via exposure to BQ and stimulation of the TGF-beta pathway, and
      elucidate the cell signaling that is involved in the etiopathogenesis of the
      disease process.

PMID- 15946179
TI  - The high prognostic value of the histologic grade at the deep invasive front of
      tongue squamous cell carcinoma.
AB  - BACKGROUND: Although many histopathologic factors in squamous cell carcinoma of
      the tongue predict the prognosis, the major predictive factors have not been
      identified clearly. This study analyzed the prognostic value of the histologic
      grade at the deep invasive front of tongue squamous cell carcinoma. METHODS: The
      clinicopathologic features of 124 consecutive patients seen between January 1985
      and December 1999 with previously untreated squamous cell carcinoma of the tongue
      were reviewed. Their mean age was 58.5 years (range: 23-90) and the male-female
      ratio was 1.8: 1 (79 men and 45 women). There were 41, 40, 30, and 13 cases at
      stage I to stage IV, respectively. The clinicopathologic factors, especially the
      histologic grade at the deep invasive front (invasive front grade, IFG), were
      analyzed to determine factors predicting prognosis. RESULTS: The 5-year disease
      free survival rate of the patients treated with curative aim only was 66.7%.
      Clinicopathologic factors significantly associated with the prognosis were T
      classification, tumor size, stage classification, tumor depth, macroscopic
      appearance, cervical lymph node metastasis (nodal metastasis), microvascular
      invasion, and IFG. In a multivariate analysis, patients with tumor depth >/=4 mm,
      IFG >/=8 points, and nodal metastasis had a reduced disease-free survival and IFG
      >/=11 points had a predictive value for nodal metastasis (odds ratio: 7.34; P =
      0.0019). CONCLUSION: This study found that a high IFG malignancy score had a high
      prognostic value for squamous cell carcinoma of the tongue.

PMID- 15946180
TI  - Immunohistochemical co-localization of lymphatics and blood vessels in oral
      squamous cell carcinomas.
AB  - BACKGROUND: Differentiating lymphatic vessels from blood vessels is difficult,
      partly due to the lack of a specific method for identifying lymphatics. A new
      lymphatic vessel-reactive antibody, D2-40 has recently become commercially
      available. We examined the selectivity of D2-40 for lymphatics in oral neoplastic
      lesions for discrimination from blood vessels. METHODS: Formalin-fixed, paraffin
      embedded sections of oral lymphangiomas (n = 3), oral hemangiomas (n = 7), and
      oral squamous cell carcinomas (OSCC, n = 46) were double immunostained with D2-40
      and anti-CD34 monoclonal antibodies (MoAb) using ENVISION-polymer technique with
      5-bromo-4-chloro-3-indoxyl-phosphate (BCIP)/nitroblue tetrazolium chloride (NBT)
      and 3,3'-diaminobenzidine (DAB) as color reagents, respectively. RESULTS: In the
      oral lymphangiomas and hemangiomas D2-40 was detected in all lymphatics, while
      all blood vessels were positive for CD34. In OSCC, number of vessels for
      lymphatics (P < 0.01) and for blood vessels in the perineoplastic areas were
      significantly greater than those in intratumoral areas. CONCLUSIONS: These
      results indicate that lymphatic proliferation might be much more extensive in the
      peritumoral area than intratumoral.

PMID- 15946181
TI  - Risk factors associated with denture stomatitis in the United States.
AB  - BACKGROUND: This study reports denture stomatitis (DS) prevalence from a large
      USA probability sample from the National Health and Nutrition Examination Survey,
      1988-1994 (NHANES III). METHODS: Oral examinations were performed on 3450
      individuals 18-90+ years of age (mean: 59.2; SD: 0.50 years), 57.7% male and
      42.3% female. Multivariable logistic regression models were fitted for DS using
      sociodemographic, denture quality, blood analytes, alcohol and tobacco use,
      history of diabetes, and current antibiotic use as covariates. Odds ratios (OR),
      adjusted for other covariates in each model (AOR) are presented. RESULTS: Of 3450
      removable denture wearers, 963 (27.9%) had DS. DS prevalence was associated with
      wearing maxillary (AOR: 6.20) and mandibular (AOR: 5.21) complete dentures
      continuously; smoking >/=15 cigarettes day (maxillary complete: AOR = 1.31;
      mandibular complete: AOR = 1.50; maxillary partial: AOR = 2.04); vitamin A
      deficiency (mandibular complete: AOR = 5.97; maxillary partial: AOR = 5.67;
      mandibular partial: AOR = 24.42). Maxillary dentures with inadequate relines had
      approximately half the OR of DS than those with adequate relines (maxillary
      complete: AOR = 0.42; mandibular complete: AOR = 0.50). CONCLUSIONS: Denture
      stomatitis prevalence is associated with the amount of tissue covered by
      dentures, low vitamin A levels, cigarette smoking, and constant denture wear.

PMID- 15946182
TI  - Expression of alpha-defensin-1 in chronic hyperplastic candidosis.
AB  - BACKGROUND: Chronic hyperplastic candidosis (CHC) represents a chronic
      opportunistic candida infection. We clarified the presence, localization and
      participation of alpha-defensin-1 in host response against chronic candidal
      stimulus. METHODS: Immunohistochemically stained CHC biopsies (n = 10) were
      compared to candida negative idiopathic leukoplakia (n = 10). RESULTS: In CHC
      alpha-defensin-1 was detected in neutrophils intravascularly, in lamina propria
      and in the epithelium, in part in intraepithelial microabscesses. Staining
      intensity of individual neutrophils varied and was associated with peri- and
      extracellular staining, in particular in the superficial epithelial cell layers.
      In controls only very few homogeneously staining neutrophils were detected
      intravascularly without any extracellular alpha-defensin-1 deposition.
      CONCLUSIONS: Neutrophils form microabscesses and respond to Candida by activation
      and release of alpha-defensin-1 to peri- and extracellular matrix. This together
      with the epithelial cell migration from the basal layer to epithelial surface
      leads to alpha-defensin-1 rich protective shield in the most superficial
      epithelial cell layers.

PMID- 15946183
TI  - Frequency, species and molecular characterization of oral Candida in hosts of
      different age in China.
AB  - INTRODUCTION: Research indicates that host age is a determining factor in yeast
      carriage. From the neonatal period, humans go through several dentition periods,
      and the emergence and substitution of teeth and changes in living habits greatly
      change the environment of the oral cavity, and therefore influence colonization
      by oral commensal organisms, certainly including Candida spp. No previous study
      of Candida carriage by different age groups divided by dentition has been
      reported. This study supplies data on the geographical specificity of C. albicans
      genotypic subgroup distribution. METHODS: All test individuals came from a single
      geographical locale over a short period. Following mucosal swab sampling,
      CHROMagar Candida-yeast differential media were used to determine the frequency
      of carriage and species. All C. albicans strains were confirmed by PCR and PCR
      using primers reported to span a transposable intron region in the 25S rRNA gene
      was used to determine genotypic subgroups. RESULTS: The results demonstrate that
      for the tested population, the frequency of Candida species and the distribution
      of C. albicans genotypic subgroups varied with age group. With increasing age,
      the frequency of C. albicans decreases, non-C. albicans yeasts increases;
      Genotypic subgroup A is the dominating strain in the oral cavities of healthy
      young individuals. CONCLUSIONS: The influence of dentition substitution on oral
      yeast carriage was minor.

PMID- 15946184
TI  - Tumor necrosis factor-alpha increases chemokine gene expression and production in
      synovial fibroblasts from human temporomandibular joint.
AB  - BACKGROUND: Synovitis, which is characterized by infiltration of inflammatory
      cells, often accompanies progression of clinical symptoms of the
      temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to
      play important roles in progression of synovitis. The purpose of this study was
      to examine production and gene expression of chemokines by synovial fibroblasts
      stimulated by tumor necrosis factor-alpha (TNF-alpha). METHODS: Protein levels of
      chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene
      expression of chemokines was analyzed by real-time polymerase chain reaction
      (PCR). RESULTS: Production of interleukin (IL)-8, growth-related oncogene (GRO)
      alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation
      normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was
      increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1alpha,
      macrophage inflammatory protein (MIP)-1alpha and -1beta were not detectable in
      conditioned media of synovial fibroblasts, with or without TNF-alpha treatment.
      Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to
      TNF-alpha treatment were detected. CONCLUSIONS: Increased protein production and
      gene expression of chemokines by synovial fibroblasts in response to TNF-alpha
      treatment appears to play an important role in recruitment of inflammatory cells
      into synovium and the progression of synovitis in the TMJ.

PMID- 15946185
TI  - Acute phase protein induction by experimental inflammation in the salivary gland.
AB  - BACKGROUND: The submandibular gland (SMG) is a major salivary gland, which plays
      an important role in maintenance the oral health. In this study, we intended to
      explore the role of the SMG's defense system of the animals in which experimental
      inflammation is induced. METHODS: The levels of mRNAs for inflammation cytokines
      and acute phase proteins were detected by reverse transcriptase-polymerase chain
      reaction (RT-PCR). RESULTS: The mRNAs for acute phase proteins were found to be
      increased in the SMG and extraorbital and intraorbital lacrimal gland (ELG and
      ILG) of rats at 24 h after subcutaneous injection of turpentine oil. The
      induction of mRNA for these inflammatory proteins by turpentine oil was preceded
      by a transient increase in the level of mRNAs for IL-1beta, IL-6 and TNF-alpha at
      6 h after subcutaneous injection of the oil. Such cytokine induction was
      similarly seen by lipopolysaccharide (LPS) injection, and involvement of Toll
      like receptor 4 (TLR4) was strongly suggested from experiment using C3H/HeJ mice,
      a TLR4-deficient mutant strain. CONCLUSION: The up-regulation of acute phase
      proteins and inflammation cytokines in the SMG, ELG and ILG by experimental
      inflammation suggests the existence of a strict defense system via the innate
      immune system in the SMG and other exocrine gland.

PMID- 15946186
TI  - Chronic GVHD in minor salivary glands and oral mucosa: histopathological and
      immunohistochemical evaluation of 25 patients.
AB  - BACKGROUND: Graft-vs.-host disease (GVHD) is the major cause of morbidity and
      mortality in patients undergoing allogeneic Bone Marrow Transplantation (BMT).
      The aim of our study was to identify the most relevant histological features for
      diagnosis of chronic Graft-vs.-Host Disease (cGVHD) in oral mucosa and minor
      salivary glands of 25 patients, as well as to evaluate the immunophenotype of the
      inflammatory cells. METHODS: Sixteen patients that were submitted to allogeneic
      BMT but did not present cGVHD were selected as a control group. The sections were
      studied on H & E and CD68, CD45, CD4, CD8, CD20 staining. RESULTS: The most
      frequent histologic findings in oral mucosa at the day of diagnosis of cGVHD
      were: hydropic degeneration of the basal layer of the epithelium, apoptotic
      bodies, lymphocytic infiltration, and focal or total cleavage between the
      epithelial and connective tissue. In the labial salivary glands (LSG),
      lymphocytic infiltration, acinar loss and fibrosis were the main alterations.
      Cytotoxic CD8-T cells and macrophages were predominant both in the epithelium and
      connective tissue, as well as in minor salivary glands. CONCLUSIONS: Histological
      features were useful in the diagnosis of oral cGVHD. It is suggested that CD8-T
      cells and macrophages play important role in the pathogenesis of the disease.

PMID- 15946187
TI  - Structural and morphometrical study in glandular parenchyma from alcoholic
      sialosis.
AB  - BACKGROUND: The aim of this work was to determine morphometrical changes in
      lingual, labial and submaxillar salivary glands from alcoholic chronics. METHODS:
      Five samples of each type of gland were obtained from autopsies of chronic
      alcoholics and equal number of samples from individuals whose death cause was
      accidental (controls). Serous acini in von Ebner and submaxillar glands and
      mucous acini in labial and Blandin-Nuhn glands were analysed. In the ductal
      system, intra and interlobular striated ducts were studied. A digital-image
      analyser was used to measure different parameters in the acini and ducts.
      RESULTS: Statistical analysis revealed that lingual and submaxillar salivary
      glands presented a significant acinar hypertrophy and hyperplasy. These changes
      were not observed in labial salivary glands. All studied glands showed
      significant structural modifications in the striated ducts. CONCLUSION: These
      results indicate that the significant variations together with the histological
      qualitative pattern could be useful as confident indicators for the differential
      histopathological diagnosis with other sialosis from different aetiology.

PMID- 15946188
TI  - Cystic lesion of the parotid following drug-induced toxic epidermal necrolysis
      (Lyell's syndrome).
AB  - A 32-year-old woman developed a unilateral cyst of the duct of parotid gland 4
      months after severe oral involvement of drug-induced toxic epidermal necrolysis
      (TEN). The pathomechanism leading to the TEN epidermal destruction had presumably
      involved the salivary epithelium as well, leading to the development of the
      cystic lesion. The patient had low serum lipase levels, but high serum amylase
      levels at the time of TEN. These serological markers could represent a clue for
      the risk of developing cystic lesions of the large salivary glands following TEN.

PMID- 15946189
TI  - Anorexia/bulimia-related sialadenosis of palatal minor salivary glands.

PMID- 15946190
TI  - A low-molecular mass ribonuclease from the brown oyster mushroom.
AB  - A ribonuclease, with a molecular mass of 9 kDa and an N-terminal sequence
      resembling the sequence of a fragment of tRNA/rRNA cytosine-C5-methylase and a
      fragment of a alanyl-tRNA synthetase, was isolated from fresh fruiting bodies of
      the brown oyster mushroom Pleurotus ostreatus. The ribonuclease was purified
      using a very simple protocol that comprised ion-exchange chromatography on
      carboxymethyl (CM)-cellulose and affinity chromatography on Affi-gel blue gel.
      Subsequent gel filtration by fast protein liquid chromatography on Superdex 75
      and sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis revealed that
      the ribonuclease was purified after the first two chromatographic steps. The
      ribonuclease was adsorbed on CM-cellulose and Affi-gel blue gel. The ribonuclease
      exhibited the highest activity toward poly A, lower activity toward poly C,
      slight activity toward poly G, and indiscernible activity toward poly U. The
      enzyme was stimulated upon exposure to 1 microm Mg2+ and 10 microm Zn2+, but was
      inhibited by the following ions at 10 mm: Ca2+, Mg2+, Zn2+, Cu2+, Fe2+, Mn2+, and
      Fe3+. The ribonuclease required a pH of 8.0 and a temperature of 50-70 degrees C
      to express maximal activity. It had a Km of 60 microm toward yeast tRNA. It
      lacked mitogenic and HIV-1 reverse transcriptase inhibiting activities, but
      exerted antiproliferative activity toward leukemia L1210 cells.

PMID- 15946191
TI  - Structure-function studies of the functional and binding epitope of the human 37
      kDa laminin receptor precursor protein.
AB  - Expression of the 37 kDa laminin receptor precursor protein (37LRP) correlates
      directly with increased invasiveness and the metastatic potential of tumors. The
      37LRP matures to a 67 kDa protein which facilitates the binding of cancer cells
      to basement membranes. The palindrome peptide sequence LMWWML, corresponding to
      the 173-178-residue stretch of the human 37LRP sequence, has been identified as
      the laminin-1-binding site. Peptides from 37LRP of species that contain this
      palindrome-bind laminin-1 with high affinity. Nuclear magnetic resonance (NMR)
      conformational studies have been undertaken on a synthetic 15-residue peptide
      (KGAHSVGLMWWMLAR) containing the palindrome to establish the structural basis of
      this activity. To further correlate the structural data with laminin-1-binding
      function, analogous structural studies were conducted for a similar peptide
      (RGKHSIGLIWYLLAR) lacking the palindrome, originating from 37LRP sequence of
      Saccharomyces cerevisiae and exhibiting low laminin-1-binding affinity. Finally,
      in vitro cell invasion assays were performed to investigate the possibility that
      the laminin-1-binding affinity of the peptides influences their inhibitory
      activity.

PMID- 15946192
TI  - Three-dimensional structure of the alpha-MSH-derived candidacidal peptide [Ac
      CKPV]2.
AB  - Previous research has shown that the immunomodulatory peptide alpha-melanocyte
      stimulating hormone (alpha-MSH) and its carboxy-terminal tripeptide KPV (Lys-Pro
      Val alpha-MSH11-13) have antimicrobial influences. By inserting a Cys-Cys linker
      between two units of KPV, we designed the dimer [Ac-CKPV]2 that showed excellent
      candidacidal effects in pilot tests and was the subject of further
      investigations. [Ac-CKPV]2 was active against azole-resistant Candida spp.
      Therefore, the molecule appeared a promising candidate for therapy of fungal
      infections and was the subject of a structural study. 1H-NMR and restrained
      mechanic and dynamic calculations suggest that the peptide adopts an extended
      backbone structure with a beta-turn-like structure. These results open a pathway
      to development of additional novel compounds that have candidacidal effects
      potentially useful against clinical infections.

PMID- 15946193
TI  - The interactions of phenytoin and its binding site in DI-S6 segment of Na+
      channel voltage-gated peptide by NMR spectroscopy and molecular modeling study.
AB  - Nuclear magnetic resonance (NMR) spectra of a model peptide (BL-DIS6), in the
      presence of anticonvulsant diphenyl drug, phenytoin (DPH), were measured to
      obtain the interactions between the selected drug and the model peptide. BL
      DIS6's sequence corresponds to the S6 segment in domain I of rat brain type IIA
      Na+-channel. NMR studies have demonstrated that the magnitude of the chemical
      shifts of amide- and alpha-protons can be used as a measurement of the complex
      stability and binding site of the peptide. Our NMR results propose a 3(10)
      helical structure for BL-DIS6, and suggest a binding cavity for DPH that involves
      the hydrophobic particles of residues Ans-7, Leu-8, Val-11, and Val-12.
      Furthermore, molecular modeling was performed to provide a possible complex
      conformation that the phenyl portion of DPH is accommodated in the proximity of
      the C-terminal residues Ala-11 and Val-12, and simultaneously the heterocyclic
      amine ring of DPH is perching at the residue Asn-7 periphery and stabilizing the
      phenyl portion deep insertion into the peptide.

PMID- 15946194
TI  - Tryptophan replacement in the nociceptin/orphanin FQ receptor ligand Ac-RYYRWK
      NH2.
AB  - In the present study we describe the in vitro pharmacological characterization of
      the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) ligand Ac-RYYRWK-NH2 and the
      synthesis and biological evaluation of 13 Trp5 substituted Ac-RYYRWK-NH2 analogs.
      Results indicate that Ac-RYYRWK-NH2 behaves as a highly potent and selective
      partial agonist at the NOP receptors and that the whole indole moiety of the Trp5
      side chain is not required, being a phenyl-ethyl side chain already sufficient
      for maintaining high potency.

PMID- 15946195
TI  - ADP-induced platelet aggregation in the microcirculation of pig myocardium and
      rabbit kidneys.

PMID- 15946196
TI  - The discovery and characterization of platelet GPIb.

PMID- 15946197
TI  - Is clopidogrel the antiplatelet drug of choice for high-risk patients with
      stroke/TIA?: Yes.

PMID- 15946198
TI  - Is clopidogrel the antiplatelet drug of choice for high-risk patients with
      stroke/TIA?: No.

PMID- 15946199
TI  - Genetic and environmental origins of the association between birth weight and
      cardiovascular risk factors.

PMID- 15946200
TI  - The effect of birth weight on clottable and intact fibrinogen levels: a twin
      study.
AB  - Several studies in singletons have found an association between low birth weight
      and increased plasma concentrations of clotting factors in adult life. Twins
      provide an opportunity to assess the possible contribution of genetic factors to
      this association. Forty-four monozygotic and 60 dizygotic same-sex twin pairs
      aged 19-50 years and 78 singleton controls matched for age, gestational age,
      gender, maternal age and parity were recruited from an obstetric database.
      Associations between both adult clottable fibrinogen (measured by the Clauss
      method) and intact fibrinogen (measured by the immunoprecipitation test), and
      birth weight were assessed by linear regression with adjustment for current age,
      gender, smoking and body mass index. Twins were significantly lighter at birth
      than singleton controls, but did not differ significantly in adult height, weight
      or fibrinogen levels from the singleton controls. There was a significant inverse
      association between birth weight and clottable fibrinogen levels among singleton
      controls [-0.22 g L(-1) kg(-1) (95% CI: -0.41,-0.03), P = 0.03], but not in
      unpaired twins. For intact fibrinogen there was no significant association with
      birth weight in either singleton controls or twins. In the within-pair analysis
      in twins there was a significant inverse association between differences in birth
      weight and clottable fibrinogen levels in dizygotic twin pairs [-0.34 g L(-1) kg(
      1) (95% CI: -0.65,-0.02), P = 0.04], but not in monozygotic twin pairs [-0.12 g
      L(-1) kg(-1) (95% CI: -0.53, 0.28), P = 0.54]. These results support the
      possibility that genetic factors may contribute to the association between low
      birth weight and clottable fibrinogen levels.

PMID- 15946201
TI  - Superficial thrombophlebitis of the legs: still a lot to learn.

PMID- 15946202
TI  - High vs. low doses of low-molecular-weight heparin for the treatment of
      superficial vein thrombosis of the legs: a double-blind, randomized trial.
AB  - In contrast with extensive information on the management of deep vein thrombosis
      of the lower extremities, little is known on the most appropriate treatment of
      the superficial vein thrombosis (SVT). In a multicenter, prospective, controlled,
      double-blind, double-dummy clinical trial, 164 consecutive patients with acute
      SVT of the great saphenous vein were randomized to receive the s.c.
      administration of either fixed prophylactic doses (2850 a-Xa IU) or body-weight
      adjusted therapeutic doses of nadroparin once daily for 1 month. The main study
      outcome was to compare the rate of asymptomatic and symptomatic extension of SVT
      and/or venous thromboembolic (VTE) complications during a 3-month follow-up
      period. Of the 81 patients randomized to the prophylactic doses, seven [8.6%; 95%
      confidence interval (CI), 3.5-17.0] developed SVT progression or VTE
      complications as compared with six of the 83 (7.2%; 95% CI, 2.8-15.1) allocated
      to the treatment group (absolute difference, 1.4; 96% CI, -6.9 to 9.7; P = 0.74).
      No patient in either group developed major bleeding. Our findings suggest that
      therapeutic doses of low-molecular-weight heparin, administered for 1 month in
      patients with SVT of the greater saphenous vein do not improve results obtained
      by prophylactic doses, administered for the same period, over a 3-month follow-up
      period.

PMID- 15946203
TI  - Anti-beta2-glycoprotein I antibody testing in the laboratory diagnosis of
      antiphospholipid syndrome.

PMID- 15946204
TI  - The presence of IgG antibodies against beta2-glycoprotein I predicts the risk of
      thrombosis in patients with the lupus anticoagulant.
AB  - BACKGROUND: Lupus anticoagulant (LA) is a strong risk factor of thrombosis.
      However, a subgroup of patients positive for LA is unaffected by thrombosis and
      currently no predictive markers are available to identify patients positive for
      LA at increased risk for thrombosis. OBJECTIVE: The aim of the study was to
      investigate whether anti-beta-2-glycoprotein I (anti-beta2GPI) or anticardiolipin
      antibodies (ACA) are associated with an increased risk of thrombosis in patients
      persistently positive for LA. PATIENTS AND METHODS: A cohort of 87 consecutive
      patients persistently positive for LA was investigated, 55 with and 32 without a
      history of thrombosis. Immunoglobulin G (IgG) and M (IgM) antibodies against
      beta2GPI and cardiolipin were determined by enzyme-linked immunoassay. RESULTS:
      Patients positive for LA with thrombosis had significantly higher levels of anti
      beta2GPI IgG (median 16.7 standard units, interquartile range 3.0-75.2, P =
      0.002) and of ACA IgG (41.1 IgG phospholipid units per mL, 8.9-109.0, P = 0.002)
      than those without thrombosis (2.6, 1.4-7.9 and 9.7, 4.6-22.1, respectively).
      Levels of anti-beta2GPI IgM and ACA IgM did not differ significantly between LA
      patients with and without thrombosis (P = 0.25 and 0.12, respectively). Elevated
      anti-beta2GPI IgG was associated with an increased risk for thrombosis (OR = 4.0,
      95% CI 1.2-13.1), especially for venous thromboembolism (OR = 5.2, 95% CI 1.5
      18.0). CONCLUSIONS: Increased levels of anti-beta2GPI IgG were associated with
      thrombosis. We conclude that anti-beta2GPI IgG levels above normal predict an
      increased risk of thrombosis in patients persistently positive for LA.

PMID- 15946205
TI  - Microparticles in type 2 diabetes mellitus.

PMID- 15946206
TI  - Pravastatin reduces fibrinogen receptor gpIIIa on platelet-derived microparticles
      in patients with type 2 diabetes.

PMID- 15946207
TI  - The adipocyte speaks: are we listening?

PMID- 15946208
TI  - On the role of plasminogen activator inhibitor-1 in adipose tissue development
      and insulin resistance in mice.
AB  - OBJECTIVES: To investigate the role of plasminogen activator inhibitor-1 (PAI-1)
      in adipose tissue development and insulin metabolism. METHODS: Aged male wild
      type (WT) or transgenic mice with adipose tissue overexpression of PAI-1 (45-55
      weeks) in 50% C57Bl/6: 50% Friend Virus B-strain (FVB) genetic background, kept
      on normal chow, were used without or with administration of a synthetic low
      molecular weight PAI-1 inhibitor (PAI-039) to the food (1 mg g(-1)) for 4 weeks.
      RESULTS: The PAI-1 transgenic mice showed somewhat lower body weight and adipose
      tissue mass than WT mice, whereas fasting insulin levels were higher. Glucose and
      insulin tolerance tests did not reveal significant differences between both
      genotypes. Addition of PAI-039 to the food did not significantly affect total
      body fat, weight of the isolated s.c. and gonadal fat territories or their
      adipocyte size and blood vessel composition in either genotype. Fasting glucose
      levels and glucose tolerance tests were, for both genotypes, comparable with
      those without inhibitor treatment. Insulin levels and insulin tolerance tests in
      WT, but not in PAI-1 transgenic mice, suggested a higher insulin sensitivity
      after inhibitor treatment (insulin level 30 min after glucose injection of 2.0 +/
      0.17 ng mL(-1) vs. 3.2 +/- 0.48 ng mL(-1) without inhibitor treatment; P =
      0.028). CONCLUSIONS: In this model, overexpression of PAI-1 moderately impaired
      adipose tissue formation without affecting glucose or insulin tolerance.
      Administration of a synthetic PAI-1 inhibitor for 4 weeks did not affect adipose
      tissue development in WT or PAI-1 transgenic mice, but induced a higher insulin
      sensitivity in WT mice.

PMID- 15946209
TI  - Prevention of venous thromboembolism after acute ischemic stroke.
AB  - Venous thromboembolism (VTE) is a common complication after acute ischemic
      stroke. When screened by 125I fibrinogen scanning or venography, the incidence of
      deep-vein thrombosis (DVT) in stroke patients is comparable with that seen in
      patients undergoing hip or knee replacement. Most stroke patients have multiple
      risk factors for VTE, like advanced age, low Barthel Index severity score or
      hemiplegia. As pulmonary embolism is a major cause of death after acute stroke,
      the prevention of this complication is of crucial importance. Prospective trials
      have shown that both unfractionated heparin (UFH) and low molecular weight
      heparin (LMWH) are effective in reducing DVT and pulmonary embolism in stroke
      patients. Current guidelines recommend the use of these agents in stroke patients
      with risk factors for VTE. Some clinicians are concerned that the rate of
      intracranial bleeding associated with thromboprophylaxis may outweigh the benefit
      of prevention of VTE. Low-dose LMWH and UFH seem, however, safe in stroke
      patients. Higher doses clearly increase the risk of cerebral bleeding and should
      be avoided for prophylactic use. Both aspirin and mechanical prophylaxis are
      suboptimal to prevent VTE. Graduated compression stockings should be reserved to
      patients with a clear contraindication to antithrombotic agents.

PMID- 15946210
TI  - Gene therapy for hemophilia: an imperative to succeed.

PMID- 15946211
TI  - Prothrombotic conditions, oral contraceptives, and the risk of ischemic stroke.
AB  - BACKGROUND: The role of inherited prothrombotic conditions, including factor V
      Leiden (FV G1691A), prothrombin G20210A, and the methylenetetrahydrofolate
      reductase (MTHFR) C677T genotype, in the pathogenesis of ischemic stroke is not
      well established. The effects of these factors may be potentiated by the use of
      oral contraceptives, analogous to observations in venous thrombosis. METHODS:
      Patients (n = 193) were women aged 20-49 years with ischemic stroke. Controls (n
      = 767) were women without arterial thrombosis stratified for age, calendar year
      of the index event, and residence. The relative risk of ischemic stroke was
      estimated with unconditional logistic regression, adjusted for stratification
      variables. FINDINGS: Factor V Leiden and MTHFR 677TT were more common in patients
      than in controls [odds ratio (OR): 1.8; 95% confidence interval (CI): 0.9-3.6
      respectively OR: 1.5; 95% CI: 0.9-2.6]. The frequency of prothrombin G20210A was
      similar in cases and controls. Carriers of FV Leiden using oral contraceptives
      had a 11.2-fold (95% CI: 4.3-29.0) higher risk of ischemic stroke than women
      without either risk factor. Women with MTHFR 677TT using oral contraceptives had
      a 5.4-fold (95% CI: 2.4-12.0) higher risk than women without these risk factors.
      INTERPRETATION: These data suggest that carriers of FV Leiden or MTHFR 677TT who
      use oral contraceptives have an increased risk of ischemic stroke. When these
      findings are confirmed, a cost-effectiveness analysis should indicate whether
      ischemic stroke could be prevented with genetic testing before the start of oral
      contraceptives.

PMID- 15946212
TI  - Age-adjusted reference limits for carotid intima-media thickness as better
      indicator of vascular risk: population-based estimates from the VITA project.
AB  - BACKGROUND: An increase of carotid intima-media thickness (CIMT) has been
      demonstrated to be associated in many studies with the subsequent risk of cardio-
      and cerebrovascular events, but the threshold level of CIMT for an increased risk
      at different ages remains uncertain. OBJECTIVES: We aimed at establishing optimal
      reference limits associated with a definite increased vascular risk in the
      general population. METHODS: A cohort of 2580 subjects was enrolled in a
      population-based cross-sectional survey. CIMT was measured on both left and right
      common carotid arteries, and age-specific, percentile-based reference ranges for
      CIMT were computed together with the Framingham risk score. RESULTS: A
      significant, steady increase of CIMT reference ranges was observed within
      different age strata. CIMT levels were linearly related with an increase of the
      Framingham risk score, but after age-adjustment only the upper CIMT quintile was
      associated with a higher Framingham risk score. CONCLUSIONS: Age-specific
      reference limits provide better estimate of vascular risk in the population and
      correlation with established risk factors.

PMID- 15946213
TI  - A prospective study of antibodies to beta2-glycoprotein I and prothrombin, and
      risk of thrombosis.
AB  - Antiphospholipid syndrome (APS) is a clinical autoimmune disorder characterized
      by thrombosis/pregnancy morbidity associated with the persistence of lupus
      anticoagulant (LA) and/or anticardiolipin (aCL) antibodies. We assessed the
      contribution of antibodies to beta2-glycoprotein I (anti-beta2GPI) and
      prothrombin (anti-PT) to the thrombotic risk in a cohort of 194 consecutive
      patients with persistent LA and/or aCL. Median follow-up was 45 months. A total
      of 39 patients (20.1%) had one documented episode of thrombosis during follow-up.
      Eleven of these patients had no previous thrombosis before enrollment in the
      study and 28 had recurrences of thrombosis. There were 21 venous and 18 arterial
      thrombotic events and the overall incidence of thrombosis was 5.6% per patient
      year. After multivariate analysis, the male sex (P = 0.025), a previous
      thrombosis (P < 0.01), the presence of anti-beta2GPI (P = 0.001), and the
      presence of anti-PT (P = 0.03) remained as independent risk factors for recurrent
      thrombosis. Only IgG anti-beta2GPI and anti-PT were associated with an increased
      risk of thrombosis (P < 0.01 and P = 0.005). Patients testing positive for anti
      beta2GPI had a higher rate of thrombosis than did antiphospholipid patients
      without anti-beta2GPI (8.0% vs. 3.1% per patient-year). Similarly, a higher rate
      of thrombosis was found in patients with positive anti-PT compared with patients
      without anti-PT (8.6% vs. 3.5% per patient-year). Considering only the group of
      142 LA positive patients, the highest incidence of thrombosis was found in LA
      patients positive for both anti-beta2GPI and anti-PT (8.4% per patient-year). In
      conclusion, the presence of IgG anti-beta2GPI and anti-PT in patients with LA
      and/or aCL and mainly in those with LA predicts a higher risk of thromboembolic
      events.

PMID- 15946214
TI  - D-Dimer test in cancer patients with suspected acute pulmonary embolism.
AB  - BACKGROUND: The safety of a D-dimer (DD) measurement in cancer patients with
      clinically suspected pulmonary embolism (PE) is unclear. OBJECTIVES: The aim of
      this study was to assess the accuracy of the DD test in consecutive patients with
      clinically suspected PE with and without cancer. METHODS: The diagnostic accuracy
      of DD (Tinaquant D-dimer) was first retrospectively assessed in an unselected
      group of patients referred for suspected PE (n = 350). Subsequently, the
      predictive value of the DD was validated in a group of consecutive inpatients and
      outpatients with clinically suspected PE prospectively enrolled in a management
      study (n = 519). The results of the DD test in cancer patients were assessed
      according to the final diagnosis of PE and the 3-month clinical follow-up.
      RESULTS: In the first study group, DD showed a sensitivity and a negative
      predictive value (NPV) of 100% and 100% in patients with cancer and 97% and 98%
      in those without malignancy, respectively. In the validation cohort, the
      sensitivity and NPV of DD were both 100% (95% CI 82%-100% and 72%-100%,
      respectively), whereas in patients without malignancy, the corresponding
      estimates were 93% (95% CI 87%-98%) and 97% (95% CI, 95%-99%), respectively. The
      specificity of DD was low in patients with (21%) and without cancer (53%).
      CONCLUSIONS: A negative DD result safely excludes the diagnosis of PE in patients
      with cancer. Because of the low specificity, when testing 100 patients with
      suspected PE, a normal DD concentration safely excludes PE in 15 patients with
      cancer and in 43 patients without cancer.

PMID- 15946215
TI  - Anti-protein S antibodies following a varicella infection: detection,
      characterization and influence on thrombin generation.
AB  - Postinfectious purpura fulminans is a rare disease. Varicella is one of the
      precipitating conditions and we recently observed such a case. The 4-year-old
      child was found to have a severe transient protein S deficiency. By enzyme-linked
      immunosorbent assay and surface plasmon resonance we first demonstrated that anti
      protein S antibodies were present and also transient. Next we characterized the
      epitopes against which these antibodies were directed and found that they
      predominantly recognized the N-terminal part of protein S. Finally we showed by
      thrombography a transient dramatic hypercoagulable state as a result of thrombin
      being unregulated by the dynamic protein C inhibitory system: in vitro thrombin
      generation, in response to a low concentration of tissue factor, was almost
      insensitive to activated protein C up to 25 nmol L(-1) on day 4 while it was
      normally sensitive on day 42. For the first time, we demonstrated a temporal
      relationship between protein S deficiency, antibodies to protein S and
      hypercoagulability, thus supporting the pathogenic role of these antibodies.

PMID- 15946216
TI  - The B domain of coagulation factor VIII interacts with the asialoglycoprotein
      receptor.
AB  - BACKGROUND: Coagulation factor VIII (FVIII) is a heavily glycosylated
      heterodimeric plasma protein that consists of a heavy (domains A1-A2-B) and light
      chain (domains A3-C1-C2). It has been well established that the clearance of
      FVIII from the circulation involves mechanisms that are sensitive to the low
      density lipoprotein receptor (LDLR) family antagonist receptor-associated protein
      (RAP), including LDLR-related protein. Because FVIII clearance in the presence of
      a bolus injection of RAP still occurs fairly efficient, also RAP-independent
      mechanisms are likely to be involved. OBJECTIVES: In the present study, we
      investigated the interaction of FVIII with the endocytic lectin
      asialoglycoprotein receptor (ASGPR) and the physiological relevance thereof.
      METHODS AND RESULTS: Surface plasmon resonance studies demonstrated that FVIII
      dose-dependently bound to ASGPR with high affinity (Kd approximately 2 nM). FVIII
      subunits were different in that only the heavy chain displayed high-affinity
      binding to ASGPR. Studies employing a FVIII variant that lacks the B domain
      revealed that FVIII-ASGPR complex assembly is driven by structure elements within
      the B domain of the heavy chain. The FVIII heavy chain-ASGPR interaction required
      calcium ions and was inhibited by soluble D-galactose. Furthermore,
      deglycosylation of the FVIII heavy chain by endoglycosidase F completely
      abrogated the interaction with ASGPR. In clearance experiments in mice, the FVIII
      mean residence time was prolonged by the ASGPR-antagonist asialo-orosomucoid
      (ASOR). CONCLUSIONS: We conclude that asparagine-linked oligosaccharide
      structures of the FVIII B domain recognize the carbohydrate recognition domains
      of ASGPR and that an ASOR-sensitive mechanism, most likely ASGPR, contributes to
      the catabolism of coagulation FVIII in vivo.

PMID- 15946217
TI  - The expression of prion protein (PrP(C)) in the megakaryocyte lineage.
AB  - BACKGROUND: Cellular prion protein (PrP(C)) is a naturally occurring protein in
      normal individuals which adopts an abnormal conformation, termed scrapie prion
      protein (PrP(Sc)) that is associated with disease. There is great concern that
      clinically asymptomatic variant Creutzfeldt-Jacob disease (vCJD) may transmit
      PrP(Sc) in blood transfusion products. PrP(C) is widely expressed and has been
      found in human blood. The majority of cellular borne PrP(C) is associated with
      platelets (84%). Although PrP(C) mRNA has been demonstrated in platelets, the
      quantity is unknown and may not reflect the total PrP(C) present. OBJECTIVE: To
      investigate the expression of PrP(C) in the megakaryocyte lineage. METHODS: The
      expression of PrP(C) was studied in CD34+ cells, cultured megakaryocytes and
      platelets using electron microscopy, flow cytometry, semi-quantitative RT-PCR and
      immunofluorescence confocal microscopy. RESULTS AND CONCLUSIONS: The expression
      of PrP(C) appeared to increase with differentiation and polyploidization in the
      megakaryocyte lineage. PrP(C) was located within platelet alpha-granules and its
      source is likely to be from megakaryocyte precursors. If PrP(Sc) has a similar
      distribution, these results have implications for the selection of blood donors
      and preparation of cell-depleted blood products.

PMID- 15946218
TI  - A tripeptide mimetic of von Willebrand factor residues 981-983 enhances platelet
      adhesion to fibrinogen by signaling through integrin alpha(IIb)beta3.
AB  - BACKGROUND: RGD is a major recognition sequence for ligands of platelet
      alpha(IIb)beta3. OBJECTIVE AND METHODS: To identify potential binding sites for
      alpha(IIb)beta3 apart from RGD, we screened phage display libraries by blocking
      the enrichment of RGD-containing phages with a GRGDS peptide and identified a
      novel integrin recognition tripeptide sequence, VPW. RESULTS: Platelets adhered
      to an immobilized cyclic VPW containing peptide in a alpha(IIb)beta3-dependent
      manner; platelets and alpha(IIb)beta3-expressing CHO cells adhered faster to
      immobilized alpha(IIb)beta3-ligands in the presence of soluble VPW. In platelets
      adhering to fibrinogen, VPW accelerated the activation of the tyrosine kinase Syk
      which controls cytoskeletal rearrangements. In alpha(IIb)beta3-expressing CHO
      cells, VPW induced a faster formation of stress fibers. Sequence alignment
      positioned VPW to V980-P981-W982 in the von Willebrand factor (vWf) A-3 domain.
      In blood from a vWf-deficient individual, VPW increased platelet adhesion to
      fibrinogen but not to collagen under flow and rescued the impaired adhesion to
      vWf deficient in A-3. CONCLUSION: These data reveal a VPW sequence that
      contributes to alpha(IIb)beta3 activation in in vitro experiments. Whether the
      V980-P981-W982 sequence in vWf shows similar properties under in vivo conditions
      remains to be established.

PMID- 15946219
TI  - A new functional assay of thrombin activatable fibrinolysis inhibitor.
AB  - New thrombin activatable fibrinolysis inhibitor (TAFI) assays are necessary for
      studying the role of this fibrinolysis inhibitor in cardiovascular disease. The
      identification of a functional single nucleotide polymorphism (SNP) (1040C/T)
      leading to a TAFI-variant with increased stability but lower antigen levels has
      made the determination of functional activity even more essential. Therefore, we
      developed a new assay for the functional activity of TAFI in citrated plasma
      samples. This assay is based on the retardation of plasma clot lysis by TAFIa.
      TAFI activation was induced simultaneously with fibrin formation and lysis was
      mediated by rt-PA. The variability of other plasma components was minimized by a
      20-fold dilution of the samples in TAFI-depleted plasma. Lysis times (-/+ potato
      carboxypeptidase inhibitor) and the TAFI-related retardation of clot lysis, the
      functional parameter of the assay, were determined in a group of 92 healthy
      volunteers, as well as TAFI antigen levels (electroimmunoassay) and two TAFI SNPs
      (-438A/G and 1040C/T). TAFI-related retardation was 19.8 +/- 5.6 min (mean +/-
      SD) and was correlated with the antigen level. The specific antifibrinolytic
      activity of TAFI was associated with the -438A/G and 1040C/T genotypes.
      Individuals with the 325Ile-variant had on average a 34% higher TAFI-specific
      antifibrinolytic activity than individuals with the 325Thr-isoform. The TAFI
      related retardation in the two groups of individuals did not differ, as a lower
      level compensated for the higher specific antifibrinolytic activity of the 325Ile
      isoform. This assay provides valuable information about the performance of
      different TAFI isoforms and constitutes a new method for studying the role of
      TAFI in cardiovascular disease.

PMID- 15946220
TI  - Role of isoleucine residues 182 and 183 in thrombin-activatable fibrinolysis
      inhibitor.
AB  - Thrombin-activatable fibrinolysis inhibitor (TAFI) is a procarboxypeptidase that,
      once activated, can attenuate fibrinolysis. The active form, TAFIa, is a labile
      enzyme, with a half-life of a few minutes at 37 degrees C. Understanding the
      molecular mechanisms of TAFIa inactivation will allow the development of
      compounds that modulate TAFIa activity. Based on their three-dimensional model of
      TAFI, Barbosa Pereira et al. [J Mol Biol (2002), vol. 321, pp. 537-547] suggested
      that Ile182 and Ile183 were involved in the instability of TAFIa. However, these
      carboxypeptidases are, unlike TAFIa, stable proteases. Therefore, we constructed,
      expressed and characterized a TAFI mutant in which Ile182 and Ile183 were changed
      into the residues found in pancreas carboxypeptidase B at corresponding
      positions, Arg and Glu. The active form of the mutant, TAFIa-I182R-I183E, had a
      similar half-life as wild-type TAFIa, showing that Ile182 and Ile183 were not
      involved in the regulation of TAFIa stability. Remarkably, however, TAFI-I182R
      I183E was activated at a lower rate by thrombin-thrombomodulin (mutant: 45 +/- 2
      U L(-1) s(-1) and wild type: 103 +/- 3 U L(-1) s(-1)), thrombin (mutant: 1 +/-0.1
      U L(-1) s(-1) and wild type 3 +/- 0.2 U L(-1) s(-1)) and plasmin (mutant: 0.8 +/-
      0.04 U L(-1) s(-1) and wild type: 5.0 +/-0.2 U L(-1) s(-1)) compared with wild
      type TAFI. Accordingly, it had a sixfold reduced antifibrinolytic potential. In
      conclusion, analysis of TAFI-I182R-I183E showed that I182 and I183 are not
      involved in TAFIa inactivation by conformational instability but that these
      residues may be involved in the activation of TAFI and stabilization of the
      fibrin clot.

PMID- 15946221
TI  - Endothelial microparticles induce formation of platelet aggregates via a von
      Willebrand factor/ristocetin dependent pathway, rendering them resistant to
      dissociation.
AB  - Endothelial microparticles (EMP) released from activated or apoptotic endothelial
      cells (EC) are emerging as useful markers for detection of EC dysfunction. Our
      recent observation that EMP carry von Willebrand factor (vWf) led us to
      investigate their interaction with platelets. EMP were incubated with normal
      washed platelets in the presence or absence of ristocetin, then platelet
      aggregates were measured by flow cytometry. In the absence of ristocetin,
      negligible EMP conjugated with platelets (< 5%) but in the presence of ristocetin
      (1 mg mL(-1)), EMP induced up to 95% of platelets to aggregate. EMP-platelet
      interaction was 80% blocked by anti-CD42b, or by 0.1 microm filtration to remove
      EMP. Platelet aggregates induced by normal plasma or high molecular weight vWf
      (Humate-P) dissociated 50% within 15-25 min following 1:20 dilution. In contrast,
      aggregates formed with EMP persisted two- to threefold longer with the same
      treatment, indicating greater stability. A similar degree of prolongation of
      dissociation was observed using plasma from thrombotic thrombocytopenic purpura
      (TTP) patients compared with normal plasma. Addition of EMP to plasma from severe
      von Willebrand disease restored his ristocetin-induced platelet aggregation.
      Multimer analysis of vWf on EMP showed unusually large vWf (ULvWf). In summary,
      EMP carries ULvWf multimers, promote platelet aggregates, and increase the
      stability of the aggregates thus formed.

PMID- 15946222
TI  - Gene therapy for hemophilia?

PMID- 15946223
TI  - Gene therapy for hemophilia?

PMID- 15946224
TI  - Gene therapy for hemophilia? Gene therapy for hemophilia is both desirable and
      achievable in the near future.

PMID- 15946225
TI  - Gene therapy for hemophilia? The debate reframed.

PMID- 15946226
TI  - Gene therapy for hemophilia?

PMID- 15946227
TI  - Gene therapy for hemophilia?

PMID- 15946228
TI  - Future perspective for the treatment of hemophilia A.

PMID- 15946229
TI  - Relatively high frequency of VWD types 3 and 2 in a cohort of Indian patients:
      the role of multimeric analysis.

PMID- 15946230
TI  - Factor V Leiden and PT G20210A mutations in cancer patients with and without
      venous thrombosis.

PMID- 15946231
TI  - A naturally occurring mutation near the C terminus of the beta-propeller of
      alpha(IIb) impair the transport of alpha(IIb)beta3 complexes from the endoplasmic
      reticulum to the Golgi apparatus.

PMID- 15946232
TI  - A case of cyclosporine-induced dural sinus thrombosis.

PMID- 15946233
TI  - More on: asymptomatic thrombophilia--a family affair.

PMID- 15946235
TI  - Preservation of phenotype in an organotypic cell culture model of a recessive
      keratinization defect of Norfolk terrier dogs.
AB  - The purpose of this study is to reproduce in vitro a recessive keratinization
      defect of Norfolk terrier dogs characterized by a lack of keratin 10 (K10)
      production. Keratinocytes from skin biopsy samples of four normal dogs and two
      affected dogs were cultured organotypically with growth factor-supplemented media
      in order to stimulate cornification. The cultured epidermis from the normal dogs
      closely resembled the normal epidermis in vivo and cornified. The cultured
      epidermis from the affected dogs displayed many phenotypic alterations identified
      in skin biopsies from dogs with this heritable defect. Immunohistochemistry and
      immunoblotting showed a marked decrease in K10 from the cultures of the affected
      keratinocytes, compared to that in K10 from the cultures of the normal
      keratinocytes. Real-time reverse transcription polymerase chain reaction
      quantitation showed a 31-fold decrease in K10, a 1.75-fold increase in K1 and a
      136-fold increase in K2e between the affected and the normal epidermis.
      Organotypic keratinocytes showed a 241-fold decrease in K10, a 31-fold decrease
      in K1 and a 1467-fold decrease in K2e between the affected and normal cultures.
      Although in vitro keratin expression did not precisely simulate in vivo, the
      morphology of the normal and the affected epidermis was largely preserved; thus,
      this culture system may provide an alternative to in vivo investigations for
      cutaneous research involving cornification.

PMID- 15946236
TI  - Expression of melanoma-associated antigens in melanoma cell cultures.
AB  - The efficiency of melanoma immunotherapy appears to depend on both melanoma- and
      immune system-specific factors. Melanoma-specific factors include melanoma
      associated antigen (MAA) expression as well as HLA class I molecule expression.
      We investigated the expression of five MAA - Melan-A/MART-1, tyrosinase, gp100,
      MAGE-1 and MAGE-3 - by means of FACS analysis in 50 melanoma cell cultures and
      compared them to the cultures of human foreskin-derived melanocytes and melanoma
      cell line UKRV-Mel2. Melan-A, tyrosinase and gp100 expression was frequently
      reduced in melanoma cell cultures, compared to that in foreskin melanocytes,
      whereas MAGE-1 and MAGE-3 expression showed variable degree of upregulation,
      compared to that in foreskin melanocytes. The expression of all tested MAA
      demonstrated high interindividual variability. We further show that cell cultures
      derived from the same tissue sample are oligoclonal in nature, by demonstrating
      the presence of up to three cell populations bearing distinct MAA profile.
      Analysing samples derived from the same patient but each at a different time
      point, we show that MAA expression profile changes over time either in positive
      (increase) or in negative (decrease) direction. Finally, we demonstrate that
      brain metastasis-derived cell cultures significantly overexpress Melan-A and MAGE
      3, compared to primary tumours and other metastatic sites (P-value range: 0.05
      0.001). Elucidation of the MAA expression patterns and the kinetics within the
      same patient as well as during the course of the disease may help improve current
      and develop new immunotherapeutic strategies.

PMID- 15946237
TI  - Effective inhibition of melanosome transfer to keratinocytes by lectins and
      niacinamide is reversible.
AB  - Skin pigmentation results in part from the transfer of melanized melanosomes
      synthesized by melanocytes to neighboring keratinocytes. Plasma membrane lectins
      and their glycoconjugates expressed by these epidermal cells are critical
      molecules involved in this transfer process. In addition, the derivative of
      vitamin B(3), niacinamide, can inhibit melanosome transfer and induce skin
      lightening. We investigated the effects of these molecules on the viability of
      melanocytes and keratinocytes and on the reversibility of melanosome-transfer
      inhibition induced by these agents using an in vitro melanocyte-keratinocyte
      coculture model system. While lectins and neoglycoproteins could induce apoptosis
      in a dose-dependent manner to melanocytes or keratinocytes in monoculture,
      similar dosages of the lectins, as opposed to neoglycoproteins, did not induce
      apoptosis to either cell type when treated in coculture. The dosages of lectins
      and niacinamide not affecting cell viability produced an inhibitory effect on
      melanosome transfer, when used either alone or together in cocultures of
      melanocytes-keratinocytes. Cocultures treated with lectins or niacinamide resumed
      normal melanosome transfer in 3 days after removal of the inhibitor, while
      cocultures treated with a combination of lectins and niacinamide demonstrated a
      lag in this recovery. Subsequently, we assessed the effect of niacinamide on
      facial hyperpigmented spots using a vehicle-controlled, split-faced design human
      clinical trial. Topical application of niacinamide resulted in a dose-dependent
      and reversible reduction in hyperpigmented lesions. These results suggest that
      lectins and niacinamide at concentrations that do not affect cell viability are
      reversible inhibitors of melanosome transfer.

PMID- 15946238
TI  - Induction of connective tissue growth factor expression by
      sphingosylphosphorylcholine in cultured human skin fibroblasts.
AB  - Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid metabolite that can
      enhance wound healing. In an effort to find downstream effectors of SPC, we
      performed microarray analysis and found that the expression of the gene for
      connective tissue growth factor (CTGF) was significantly affected in human skin
      fibroblasts cultured in vitro. Northern blot analysis showed that SPC markedly
      induced CTGF mRNA expression in a dose- and time-dependent manner. Consistent
      with this result, Western blot analysis also showed that SPC significantly
      induced the CTGF production. Pretreatment with cycloheximide did not prevent the
      CTGF induction by SPC, indicating that SPC stimulates CTGF mRNA expression
      without the increased synthesis of a regulatory protein. Inhibition by
      pretreatment with Y27632, but not by PD98059 (a mitogen-activated protein kinase
      1/2 inhibitor) and LY294002 (a phosphatidylinositol 3-kinase inhibitor),
      indicated that rho-kinase pathway was involved in SPC-induced CTGF expression.
      Together, these results reveal the potential importance of CTGF induction as a
      downstream event in SPC-induced cellular responses.

PMID- 15946239
TI  - Assessment of platelet activity as expressed by plasma levels of platelet factor
      4 and beta-thromboglobulin in patients with chronic idiopathic urticaria.
AB  - Blood platelet significance in inflammation is recognized but poorly
      characterized in urticaria. It is known that platelets are activated during
      inflammatory processes and are involved in modulating inflammatory and immune
      response via various mediator release. The aim of our study was to investigate
      the functional state of platelets, expressed by release reaction of C-X-C
      chemokines such as platelet factor 4 (PF-4) and beta-thromboglobulin (beta-TG) in
      chronic idiopathic urticaria (CIU). Plasma levels of PF-4 and beta-TG, which are
      established markers of in vivo platelet activation and which play important role
      in inflammatory processes, were measured by enzyme-linked immunosorbent assay in
      19 patients with CIU and in 25 healthy subjects. Mean plasma PF-4 level in CIU
      patients and control subjects was 5.01 +/- 1.67 and 4.13 +/- 2.05 IU/ml,
      respectively, whereas that for beta-TG was 29.3 +/- 14.0 and 25.2 +/- 12.6 IU/ml,
      respectively. In our small study, there have been no significant differences
      found between the members of the control and CIU group regarding plasma levels of
      PF-4 and beta-TG. Further studies should be performed to elucidate whether any
      systemic platelet activation occurs in CIU.

PMID- 15946240
TI  - Epidermal growth factor (EGF)-mediated DNA-binding activity of AP-1 is attenuated
      in senescent human epidermal keratinocytes.
AB  - The proliferative responses of cells to mitogens decrease during aging, and this
      may result from age-related defects in signal transduction in response to
      mitogens. In this study, we have investigated the age-related alteration of
      responses to epidermal growth factor (EGF) in cultured human keratinocytes that
      were senesced in vitro by repeated passage. The stimulation with EGF increased
      the DNA-binding activity of activator protein 1 (AP-1), an important
      transcription factor for cell proliferation, in young keratinocytes, whereas the
      binding activity showed little or slight change in the senescent cells. The
      induced DNA-binding activity of AP-1 in young cells was inhibited by PD 98059, an
      inhibitor of MEK, and partially inhibited by GF 109203X, an inhibitor of protein
      kinase C. Western blot analysis demonstrated that EGF induced dramatic increase
      in the phosphorylation of EGF receptor (EGFR) and extracellular signal-regulated
      kinases (ERK) in young cells, while this phosphorylation was much less profound
      in senescent cells. Finally, the application of EGF to young cells resulted in
      increased phosphorylation of Fra-2, a Fos protein component of the Jun/Fos
      heterodimer AP-1 complex. This EGF-induced Fra-2 phosphorylation was attenuated
      in senescent cells. Taken together, our study suggests that the signal
      transduction mediated by EGF/ERK pathway is altered in senescent human
      keratinocytes, and this change may be attributed, in part, to the decreased AP-1
      transcription activity observed in senescent keratinocytes.

PMID- 15946241
TI  - Pigmentation in basal cell carcinoma involves enhanced endothelin-1 expression.
AB  - Basal cell carcinoma (BCC) is the most prevalent malignant skin tumor. In Asian
      patients, marked pigmentation in BCC lesions is often observed. Recently,
      endothelins (ETs) have been implicated to participate in the pigmentation process
      of BCC. Therefore, we set out to investigate the involvement of ET in the
      pigmentation process of BCC and the potential regulators in the pigmentation
      pathway. We explored the effects of an established BCC cell line on melanocytes.
      The growth factor profiles of BCC culture supernatant and effects of supernatant
      on melanocytes were documented. Potential regulators involved in the pigmentation
      pathway were also studied. The immunohistochemical staining of pigmented and non
      pigmented BCC specimens was performed to confirm our in vitro findings. Our
      results showed that BCC supernatant contained significant amount of ET-1, basic
      fibroblast growth factor, and nerve growth factor. Furthermore, BCC supernatant
      stimulated melanin formation of cultured melanocytes. Addition of ET-receptor
      antagonist abrogated the melanogenic effect of BCC supernatant on melanocytes.
      Introduction of UVB irradiation decreased the ET-1 secretion by BCC cells.
      Immunohistochemical staining of the pigmented facial BCC specimens showed
      prominent expression of ET-1 on pigmented BCC, while the non-pigmented facial BCC
      specimens showed little ET-1 reactivity. Tumor necrosis factor-alpha (TNF-alpha)
      staining showed little expression on BCC specimens, regardless of pigmentation
      status. In summary, our results indicate that enhanced ET-1 expression in
      pigmented BCC plays an important role in the hyperpigmentation of this tumor.
      Moreover, this enhanced ET-1 cascade showed little correlation with UV
      irradiation and TNF-alpha expression in our study.

PMID- 15946242
TI  - Characterization of transgenic mice with the expression of phenylalanine
      hydroxylase and GTP cyclohydrolase I in the skin.
AB  - Phenylketonuria (PKU) is a metabolic disease causing increased levels of
      phenylalanine in blood and body fluids. Circulating phenylalanine is normally
      cleared by phenylalanine hydroxylase (PAH) expressed in the liver. The aim of
      this study is to exploit the skin as a 'metabolic sink' removing phenylalanine
      from the blood. We have previously showed that the overexpression of PAH and GTP
      cyclohydrolase I (GTP-CH), the rate-limiting enzyme in the synthesis of the
      cofactor for PAH, leads to high levels of phenylalanine clearance in primary
      human keratinocytes. In this study, we have investigated the 'metabolic sink'
      strategy in an in vivo model by developing three lines of transgenic mice
      expressing PAH and GTP-CH in various layers of the skin. The promoters used were
      keratin 14 (K14), involucrin (INV) and a truncated variant of Keratin 1 (K1). The
      mice were crossbred to a mouse model of human PKU, the PAH(enu2) mouse, in order
      to obtain mice that do not express PAH in the liver and the kidney. Transgenic
      mice containing the INV and K14 promoters expressed PAH and GTP-CH in the
      epidermis. However, the K1 promoter did not lead to detectable gene expression.
      Analysis of the mice showed that no phenotypic effect was observed in mice
      expressing PAH and GTP-CH from the INV promoter. However, low level of
      phenylalanine clearance was observed in mice expressing PAH and GTP-CH from the
      K14 promoter, suggesting that the skin can be genetically engineered to function
      as a 'metabolic sink'.

PMID- 15946243
TI  - Definition of anti-tyrosinase MAb T311 linear determinant by proteome-based
      similarity analysis.
AB  - Using non-self discrimination as a driving force in generating peptide
      immunogenicity, we have developed a computer-assisted proteomic analysis in order
      to identify the protein antigenic regions that have evoked humoral response. The
      purpose of this study was to further validate the computational analysis for
      melanoma-associated antigens and, at the same time, to assess the efficacy of the
      methodology in defining antigenic regions of autoantigens associated to
      autoimmune diseases. To achieve this two-fold objective, we have examined the
      enzyme tyrosinase, a protein that represents an important autoantigen in patients
      with vitiligo or melanoma. Here, we report that the antigenic linear determinant
      of the monoclonal antibody (Mab) T311 raised against the melanoma/vitiligo
      tyrosinase autoantigen is located in the low similarity 15-mer amino acid
      sequence tyrosinase 233-247 IPYWDWRDAEKCDIC, within the fragment 237-247. These
      data confirm non-similarity to the host proteome as a factor that participates in
      shaping peptide immune reactivity and may be a first step towards designing
      tyrosinase antigenic peptides to be used for (i) direct neutralization of harmful
      melanocytes-attacking autoantibodies in vitiligo, or (ii) production of
      antibodies against tyrosinase-positive melanomas. Moreover tyrosinase peptide
      antigens might be used as key tools in studying the boundaries between self
      tolerance and autoimmunity phenomena.

PMID- 15946244
TI  - Candida albicans-specific lymphoproliferative and cytokine (IL-4 and IFN-gamma)
      responses in atopic eczema dermatitis syndrome. Evidence of CD4/CD8 and
      CD3/CD16+CD56 ratio elevations in vitro.
AB  - BACKGROUND: Hypersensitivity to cross-reactive mannan polysaccharide allergens of
      saprophytic yeasts is likely to be involved in the pathogenesis of atopic eczema
      dermatitis syndrome (AEDS). Mannans induce elevated specific immunoglobulin E and
      lymphoproliferative responses in peripheral blood mononuclear cells (PBMCs). To
      gain more detailed data of the involvement of different subpopulations of PBMCs
      in AEDS after mannan stimulation, changes in the cell-surface marker distribution
      were analysed. METHODS: The Ficoll-isolated PBMCs of eight yeast hypersensitive
      AEDS patients and seven non-AEDS controls were stimulated in vitro by mannan
      (CAM) or whole extract antigen [In-House Reference (IHR)] of Candida albicans or
      tuberculin [purified protein derivative (PPD)] and after immunofluorescence
      staining analysed by flow cytometry. The expression of cytokine mRNA was measured
      by kinetic real-time polymerase chain reaction (TaqMan). RESULTS: After 7-day
      antigen stimulation, there were significant increases in the CD3/CD16(+)CD56
      ratio (P = 0.028 with mannan and P = 0.006 with IHR), CD4/CD8 ratio (P = 0.049
      with mannan) and interleukin-4/interferon-gamma (IL-4/IFN-gamma) mRNA ratio (P =
      0.028 with IHR) and a decrease in the CD3/CD19 ratio (P = 0.035 with mannan) of
      AEDS patients' PBMCs as compared with healthy controls' cells. These changes were
      not seen in cultures with PPD. CONCLUSIONS: The observed CAM and IHR-induced
      elevations in T cell/natural killer cell, CD4/CD8 and IL-4/IFN-gamma ratios
      suggest that C. albicans-induced TH(2)-type responses can also play a role in
      AEDS.

PMID- 15946246
TI  - Close encounters of the monoamine kind: immune cells betray their nervous
      disposition.
AB  - Here we review the evidence for immune cells expressing multiple components of
      the serotonergic and dopaminergic systems that are more commonly associated with
      the central nervous system (CNS). We discuss where and how peripheral encounters
      with these biogenic monoamines occur and posit reasons as to why the immune
      system would wish to deploy these pathways. A full taxonomy of serotonergic and
      dopaminergic constituents and their workings in component cells of the immune
      system should facilitate the formulation of novel therapeutic approaches in
      diseases characterized by immune dysfunction and potentially provide a range of
      surrogate peripheral markers for registering and monitoring disturbances within
      the CNS.

PMID- 15946247
TI  - Signalling mechanisms underlying subversion of the immune response by the
      filarial nematode secreted product ES-62.
AB  - Secretion of immunomodulatory molecules is a key strategy employed by pathogens
      to enable their survival in host organisms. For example, arthropod-transmitted
      filarial nematodes, which achieve longevity within the infected host by
      suppressing and modulating the host immune response, produce excretory-secretory
      (ES) products that have been demonstrated to possess immunomodulatory properties.
      In this review we discuss the immunomodulatory effects of the phosphorylcholine
      containing filarial nematode-secreted glycoprotein ES-62 and describe the
      intracellular signal transduction pathways it targets to achieve these effects.

PMID- 15946248
TI  - Activated CD4+ CD25+ T cells suppress antigen-specific CD4+ and CD8+ T cells but
      induce a suppressive phenotype only in CD4+ T cells.
AB  - CD4(+) CD25(+) regulatory T cells are increasingly recognized as central players
      in the regulation of immune responses. In vitro studies have mostly employed
      allogeneic or polyclonal responses to monitor suppression. Little is known about
      the ability of CD4(+) CD25(+) regulatory T cells to suppress antigen-specific
      immune responses in humans. It has been previously shown that CD4(+) CD25(+)
      regulatory T cells anergize CD4(+) T cells and turn them into suppressor T cells.
      In the present study we demonstrate for the first time in humans that CD4(+)
      CD25(+) T cells are able to inhibit the proliferation and cytokine production of
      antigen specific CD4(+) and CD8(+) T cells. This suppression only occurs when
      CD4(+) CD25(+) T cells are preactivated. Furthermore, we could demonstrate that
      CD4(+) T-cell clones stop secreting interferon-gamma (IFN-gamma), start to
      produce interleukin-10 and transforming growth factor-beta after coculture with
      preactivated CD4(+) CD25(+) T cells and become suppressive themselves.
      Surprisingly preactivated CD4(+) CD25(+) T cells affect CD8(+) T cells
      differently, leading to reduced proliferation and reduced production of IFN
      gamma. This effect is sustained and cannot be reverted by exogenous interleukin
      2. Yet CD8(+) T cells, unlike CD4(+) T cells do not start to produce
      immunoregulatory cytokines and do not become suppressive after coculture with
      CD4(+) CD25(+) T cells.

PMID- 15946249
TI  - The phenotype of type 1 and type 2 CD8+ T cells activated in vitro is affected by
      culture conditions and correlates with effector activity.
AB  - We used various culture conditions to generate type 1 (Tc1) or type 2 (Tc2)
      cytotoxic T cells in vitro. T-cell receptor (TCR) transgenic T cells were
      cultured with antigen and spleen cells, or antigen and dendritic cells (DC), or
      anti-CD3 and anti-CD28. Tc1 cultures contained interleukin (IL)-2 and IL-6, and
      Tc2 cultures contained IL-2, IL-6 and IL-4. Tc2 cells generated in each culture
      condition acquired a CD62L(low) CD44(high) phenotype, had high cytotoxic
      activity, and secreted IL-4, IL-5 and moderate amounts of interferon-gamma (IFN
      gamma). In contrast, the phenotype and function of Tc1 cells varied depending on
      culture conditions. Tc1 cells from anti-CD3 and anti-CD28 cultures had high
      cytotoxic activity and were CD62L(low) CD44(high), while Tc1 cells from antigen
      and spleen cell cultures had low cytotoxic activity and were CD62L(high)
      CD44(low). Tc1 cells from antigen and DC cultures had an intermediate phenotype.
      All Tc1 cells secreted high amounts of IFN-gamma, but only Tc1 from anti-CD3 and
      anti-CD28 cultures had antitumour activity in vivo. Differences were not caused
      by suboptimal culture conditions, as Tc1 cells divided at a similar rate whether
      cultured with antigen and spleen cells or with anti-CD3 and anti-CD28. We
      conclude that IL-4 not only induces 'type 2' cytokine secretion in CD8(+) T
      cells, but also affects their expression of surface markers and cytotoxic
      activity.

PMID- 15946250
TI  - Maintenance of long-term tumour-specific T-cell memory by residual dormant tumour
      cells.
AB  - LacZ (Gal)-reactive immune cells were transferred into athymic nu/nu mice
      inoculated with Gal-expressing syngeneic tumour cells (ESbL-Gal) in order to
      study tumour-protective T-cell memory. This transfer prevented tumour outgrowth
      in recipients and resulted in the persistence of a high frequency of Gal-specific
      CD8(+) T cells in the bone marrow and spleen. In contrast, such Ag-specific
      memory CD8(+) T cells were not detectable by peptide-major histocompatibility
      complex (MHC) multimer staining in animals that had not previously received an
      antigenic challenge. Even though CD44(hi) memory T cells from the bone marrow
      showed a significantly higher turnover rate, as judged by bromodeoxyuridine
      (BrdU) incorporation, than respective cells from spleen or lymph nodes, as well
      as in comparison to CD44(lo) naive T cells, these findings suggest that tumour
      associated antigen (TAA) from residual dormant tumour cells are implicated in
      maintaining high frequencies of long-term surviving Gal-specific memory CD8(+) T
      cells. Memory T cells could be recruited to the peritoneal cavity by tumour
      vaccination of immunoprotected nu/nu mice and exhibited ex vivo antitumour
      reactivity. Long-term immune memory and tumour protection could be maintained
      over four successive transfers between tumour-inoculated recipients, which
      involved periodic antigenic restimulation in vivo prior to reisolating the cells
      for adoptive transfer. Using a cell line (ESbL-Gal-BM) that was established from
      dormant tumour cells isolated from the bone marrow of immunoprotected animals, it
      could be demonstrated that the tumour cells had up-regulated the expression of
      MHC class I molecules and down-regulated the expression of several adhesion
      molecules during the in vivo passage. Our results suggest that the bone marrow
      microenvironment has special features that are of importance for the maintenance
      of tumour dormancy and immunological T-cell memory, and that a low level of
      persisting antigen favours the maintenance of Ag-specific memory T cells over
      irrelevant memory T cells.

PMID- 15946251
TI  - Multivalent recombinant proteins for probing functions of leucocyte surface
      proteins such as the CD200 receptor.
AB  - CD200 (OX2) is a membrane glycoprotein that interacts with a structurally related
      receptor (CD200R) involved in the regulation of macrophage function. The
      interaction is of low affinity (K(D) approximately 1 microm) but can be detected
      using CD200 displayed in a multivalent form on beads or with dimeric fusion
      proteins consisting of the extracellular region of CD200 and immunoglobulin Fc
      regions. We prepared putative pentamers and trimers of mouse CD200 with sequences
      from cartilage oligomeric matrix protein (COMP) and surfactant protein D (SP-D),
      respectively. The COMP protein gave high-avidity binding and was a valuable tool
      for showing the interaction whilst the SP-D protein gave weak binding. In vivo
      experiments showed that an agonistic CD200R monoclonal antibody caused some
      amelioration in a model of experimental autoimmune encephalomyelitis but the COMP
      protein was cleared rapidly and had minimal effect. Pentameric constructs also
      allowed detection of the rat CD48/CD2 interaction, which is of much lower
      affinity (K(D) approximately 70 microm). These reagents may have an advantage
      over Fc-bearing hybrid molecules for probing cell surface proteins without side
      effects due to the Fc regions. The CD200-COMP gave strong signals in protein
      microarrays, suggesting that such reagents may be valuable in high throughput
      detection of weak interactions.

PMID- 15946252
TI  - Integrin CD11a cytoplasmic tail interacts with the CD45 membrane-proximal protein
      tyrosine phosphatase domain 1.
AB  - Leucocyte adhesion receptor integrin CD11aCD18 and the transmembrane receptor
      like protein tyrosine phosphatase (RPTP) CD45 mediate immune synapse formation
      and signalling during antigen presentation. Previous cocapping studies on human
      naive T cells demonstrate an interaction between CD11aCD18 and CD45. CD45 cross
      linking also has an effect on the ligand-binding activity of CD11aCD18. However,
      the mode of interaction between CD11aCD18 and CD45 remains unclear. Herein, yeast
      two-hybrid analysis identified a partial CD45 cytoplasmic tail interacting with
      that of CD11a. The CD45 cytoplasmic tail comprises a membrane proximal (Mp)
      region, protein tyrosine phosphatase domain 1 (D1), spacer, D2, and carboxyl
      terminus. CD45 Mp-D1 was found to be the main interacting region for the CD11a
      cytoplasmic tail. In contrast, the full-length CD45 cytoplasmic tail interacted
      weakly with that of CD11a. It has been reported that CD45 Mp-D1 but not the full
      length cytoplasmic tail forms a homodimer whose enzymatic activity is inhibited.
      Our in vitro binding and enzymatic assays showed that the homodimeric CD45
      cytoplasmic tail interacts with that of CD11a. The biological function of CD45
      dimerization and its association with CD11a remains to be investigated.

PMID- 15946253
TI  - Expression of regulator of G protein signalling proteins in natural killer cells,
      and their modulation by Ly49A and Ly49D.
AB  - The small GTPase accelerators regulator of G protein signalling (RGS) proteins
      are important regulators of proximal signalling from G protein coupled receptors.
      Although natural killer (NK) cells express a number of G-protein coupled
      receptors, expression of RGS proteins has not been investigated. We analysed the
      expression of RGS proteins in rat NK cells, and detected mRNA for RGS1, RGS2,
      RGS5, RGS8, RGS16, and RGS18. Interestingly, when we included a panel of
      different leucocyte subsets, we found that RGS8 was selectively expressed by NK
      cells. NK cells are under control of both activating and inhibitory receptors
      and, utilizing a xenogeneic system where the mouse activating Ly49D or inhibitory
      Ly49A receptors were transfected into the rat RNK-16 cell line, the potential
      regulation of RGS proteins by single NK cell receptors was studied. We found that
      ligation of Ly49D led to a rapid and transient increase in message for RGS2,
      while Ly49A ligation up-regulated RGS2, RGS16, and RGS18 mRNA. Both receptors
      also induced a prolonged increase in RGS2 endogenous protein levels. These
      findings suggest that RGS proteins may be influenced by or involved in NK cell
      receptor events, suggesting a crosstalk between G-protein coupled receptors and
      NK cell receptors.

PMID- 15946254
TI  - Lipoteichoic acid induces nuclear factor-kappaB activation and nitric oxide
      synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW
      264.7 macrophages.
AB  - We previously demonstrated that lipoteichoic acid (LTA) might activate
      phosphatidylcholine-phospholipase C (PC-PLC) and phosphatidylinositol
      phospholipase C (PI-PLC) to induce protein kinase C activation, which in turn
      initiates nuclear factor-kappaB (NF-kappaB) activation and finally induces
      inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) release
      in RAW 264.7 macrophages. In this study, we further investigated the roles of
      tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt, and p38 mitogen
      activated protein kinase (MAPK) in LTA-induced iNOS expression and NO release in
      RAW 264.7 macrophages. Tyrosine kinase inhibitors (genistein and tyrphostin
      AG126), PI3K inhibitors (wortmannin and LY 294002), and a p38 MAPK inhibitor (SB
      203580) attenuated LTA-induced iNOS expression and NO release in concentration
      dependent manners. Treatment of RAW 264.7 macrophages with LTA caused time
      dependent activations of Akt and p38 MAPK. The LTA-induced Akt activation was
      inhibited by wortmannin, LY 294002, genistein, and tyrphostin AG126. The LTA
      induced p38 MAPK activation was inhibited by genistein, tyrphostin AG126,
      wortmannin, LY 294002, and SB 203580. The LTA-induced formation of an NF-kappaB
      specific DNA-protein complex in the nucleus was inhibited by wortmannin, LY
      294002, genistein, tyrphostin AG126, and SB 203580. Treatment of macrophages with
      LTA caused an increase in kappaB-luciferase activity, and this effect was
      inhibited by tyrphostin AG126, wortmannin, LY 294002, the Akt dominant negative
      mutant (AktDN), and SB 203580. Based on those findings, we suggest that LTA might
      activate the PI3K/Akt pathway through tyrosine kinase to induce p38 MAPK
      activation, which in turn initiates NF-kappaB activation, and ultimately induces
      iNOS expression and NO release in RAW 264.7 macrophages.

PMID- 15946255
TI  - The flavonoid luteolin prevents lipopolysaccharide-induced NF-kappaB signalling
      and gene expression by blocking IkappaB kinase activity in intestinal epithelial
      cells and bone-marrow derived dendritic cells.
AB  - The nuclear factor (NF)-kappaB transcriptional system is a major effector pathway
      involved in inflammation and innate immune responses. The flavonoid luteolin is
      found in various herbal extracts and has shown anti-inflammatory properties.
      However, the mechanism of action and impact of luteolin on innate immunity is
      still unknown. We report that luteolin significantly blocks lipopolysaccharide
      (LPS)-induced IkappaB phosphorylation/degradation, NF-kappaB transcriptional
      activity and intercellular adhesion molecule-1 (ICAM-1) gene expression in rat
      IEC-18 cells. Using chromatin immunoprecipitation, we demonstrate that LPS
      induced RelA recruitment to the ICAM-1 gene promoter is significantly reduced in
      luteolin-treated cells. Moreover, in vitro kinase assays show that luteolin
      directly inhibits LPS-induced IkappaB kinase (IKK) activity in IEC-18 cells.
      Using bone-marrow derived dendritic cells (BMDCs) isolated from interleukin (IL)
      10(-/-) mice or from recently engineered transgenic mice expressing the enhanced
      green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB
      cis-elements (cis-NF-kappaB(EGFP)), we found that luteolin blocks LPS-induced
      IkappaB phosphorylation and IKK activity, and decreases EGFP, IL-12 and tumour
      necrosis factor-alpha gene expression. Moreover, intraperitoneal administration
      of luteolin significantly inhibited LPS-induced EGFP expression in both
      peripheral blood mononuclear cells and splenocytes isolated from cis-NF
      kappaB(EGFP) mice. These results indicate that luteolin blocks LPS-induced NF
      kappaB signalling and proinflammatory gene expression in intestinal epithelial
      cells and dendritic cells. Modulation of innate immunity by natural plant
      products may represent an attractive strategy to prevent intestinal inflammation
      associated with dysregulated innate immune responses.

PMID- 15946256
TI  - Subset-dependent modulation of dendritic cell activity by circovirus type 2.
AB  - Viral interactions with dendritic cells (DCs) have important consequences for
      immune defence function. Certain single-stranded DNA viruses that associate with
      a number of species, including humans and pigs, exhibit interesting
      characteristics in this context. Porcine circovirus type 2 (PCV2) can persist
      within myeloid DCs in the absence of virus replication. Internalization was
      observed with both conventional blood DCs and plasmacytoid DCs [natural
      interferon-producing cells (NIPCs)], as well as DC precursors. This PCV2-DC
      interaction neither induced nor inhibited DC differentiation. The maturation of
      myeloid DCs induced by a cocktail of interferon-alpha/tumour necrosis factor
      alpha (IFN-alpha/TNF-alpha), and the ability to process and present antigen to T
      lymphocytes, remained intact in the presence of PCV2. The virus was clearly
      internalized by the DCs, a process noted with both mature and immature cells.
      This suggested a non-macropinocytic uptake, confirmed by an insensitivity to
      wortmannin but sensitivity to cytochalasin D, chlorpromazine and bafilomycin.
      Nevertheless, PCV2 was immunomodulatory, being effected through the reaction of
      NIPC to danger signals. When NIPCs responded to the CpG-oligonucleotide (CpG
      ODN), their costimulatory function which induces myeloid DC maturation was
      clearly impaired by the presence of PCV2. This was caused by a PCV2-induced
      inhibition of the IFN-alpha and TNF-alpha normally produced following interaction
      with CpG-ODN. Thus, the immunomodulatory activity of PCV2 is mediated through the
      disruption of NIPC function. This would impair the maturation of associated
      myeloid DC and have major implications for the efficient recognition of viral and
      bacterial danger signals, favouring the establishment of infections additional to
      that of PCV2.

PMID- 15946257
TI  - Supplementation of CXCL12 (CXCL12) induces homing of CD11c+ dendritic cells to
      the spleen and enhances control of Plasmodium berghei malaria in BALB/c mice.
AB  - In malaria, parasitaemia is controlled in the spleen, a multicomponent organ that
      undergoes changes in its cellular constituents to control the parasite. During
      this process, dendritic cells (DCs) orchestrate the positioning of effector cells
      in a timely manner for optimal parasite clearance. We have recently demonstrated
      that CXCL12 [stromal cell-derived factor-1 (CXCL12)] supplementation partially
      restores the ability to control parasitaemia in Plasmodium berghei-infected mice.
      In the present study, we investigated the nature of the DCs involved by flow
      cytometry and immunohistochemistry of CD11c(+) cells. Flow cytometry of bone
      marrow cells showed that infection with P. berghei did not alter the proportion
      of CD11c(+) cells present in this haematopoietic compartment, while CXCL12
      supplementation of naive uninfected mice induced only minor increases in the
      population of CD11c(+) cells. In the spleen, P. berghei infection alone resulted
      in an increase in CD11c(+) cells as compared with naive animals. Exogenously
      administered CXCL12 in the absence of infection resulted in a significant
      expansion of the splenic CD11c(+) population, and this effect was even more
      pronounced in infected and supplemented mice. Immunohistochemistry revealed that
      CD11c(+) cells infiltrated the perivascular areas and marginal zone of the spleen
      in infected animals treated with CXCL12, suggesting that this chemokine induces
      homing of CD11c(+) dendritic cells to the splenic compartment. Our results show
      that small amounts of CXCL12 supplementation are effective in recruiting DCs to
      the spleens of both uninfected and infected mice, suggesting the participation of
      CXCL12 and CD11c(+) cells in the establishment of an adequate environment in the
      spleen for malaria control.

PMID- 15946258
TI  - Inhibition of immunoglobulin E synthesis through Fc gammaRII (CD32) by a
      mechanism independent of B-cell receptor co-cross-linking.
AB  - The inhibitory effect on antibody production by immune complexes has been shown
      to depend on co-ligation of the B-cell antigen receptor (BCR) with the low
      affinity receptor for immunoglobulin G (IgG) (Fc gammaRIIb, CD32). Here we report
      that immunoglobulin E (IgE) synthesis, induced in a BCR-independent manner by
      interleukin-4 (IL-4) and anti-CD40 antibody, was inhibited by CD32 ligation. The
      observed effect was specific for CD32 as, first, antibodies directed against
      other B-cell surface structures had no inhibitory effect, and, second, treatment
      with anti-CD32 of cells that had been in culture for 2 days was ineffective owing
      to the down-regulation of CD32 expression. IgE inhibition was also observed in
      cells stimulated by IL-4/CD40 F(ab')(2) or IL-4 plus soluble CD40 ligand,
      demonstrating that co-cross-linking of CD32 and CD40 was not necessary to induce
      inhibition. Mechanistic studies into the IgE class switch process demonstrated
      that IL-4/anti-CD40-induced IgE germline gene transcription and B-cell
      proliferation were not affected by CD32 ligation. The data demonstrate that the
      negative regulatory role of the CD32 molecule is not restricted to BCR-induced B
      cell activation, but is also functional on other B-cell activation pathways
      mediated by CD40 and IL-4.

PMID- 15946259
TI  - Ethnic variation of Fc gamma receptor polymorphism in Sami and Norwegian
      populations.
AB  - Receptors for the Fc domain of IgG (Fc gammaR) play a critical role in linking
      cellular and humoral immunity. The various Fc gammaR genotypes may contribute to
      differences in infectious and immune-related diseases in various ethnic
      populations. The Samis are the aboriginal inhabitants of Norway and
      Fennoscandinavia and differ ethnically from the Norwegians. The distribution of
      various immune-related diseases has been reported to differ between Sami and
      Norwegians. This is the first study to evaluate the distribution of Fc gammaR
      polymorphisms in a Sami population. Two hundred Samis were genotyped for
      polymorphisms in the Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB genes. The
      genotype and allele frequencies were compared with those of 272 healthy
      Norwegians. The Sami and Norwegian Fc gammaRIIA, Fc gammaRIIIA and Fc gammaRIIIB
      genotypes differed significantly. The Samis had higher frequencies of the Fc
      gammaRIIa-H/H131, Fc gammaRIIIa-F/F158 and Fc gammaRIIIb-NA1/NA1 genotypes. The
      Fc gammaR genotypes were non-randomly distributed in both populations. These
      findings may be important for the prevalence of autoimmune and infectious
      diseases in the two populations.

PMID- 15946260
TI  - Circulating anti-retinal antibodies as immune markers in age-related macular
      degeneration.
AB  - Age-related macular maculopathy (ARM) and age-related macular degeneration (AMD)
      are the leading causes of blindness in the Western world. Despite the magnitude
      of this clinical problem, very little is known about the pathogenesis of the
      disease. In this study, we analysed the sera (using indirect immunohistochemistry
      and Western blot analysis) from a very large cohort of such patients and normal
      age-matched controls to detect circulating anti-retinal antibodies. Patients with
      bilateral drusen (n = 64) and with chorioretinal neovascularization (CNV) (n =
      51) were recruited in addition to age-matched control subjects (n = 39). The sera
      were analysed for anti-retinal immunoglobulins on retinal sections. The data were
      then correlated with the clinical features graded according to the International
      Classification and Grading System of ARM and AMD. The sera of patients with
      drusen (93.75%) and CNV (82.27%) were found to have a significantly (P = 0.02)
      higher titre of autoantibodies to the retina in comparison with controls (8.69%),
      indicating significant evidence of involvement of the immune process in early
      stages of AMD. Subsequent statistical analysis of the drusen group showed
      significant progressive staining (P = 0.0009) in the nuclei layers from early to
      late stages of ARM. Western blotting confirmed the presence of anti-retinal
      immunoglobulins to retinal antigens. As anti-retinal immunoglobulins are present
      in patients with bilateral drusen and exudative AMD, these antibodies could play
      a significant role in the pathogenesis of AMD. Whilst we do not have evidence
      that these antibodies precede disease onset, the possibility that their presence
      might contribute to disease progression needs to be investigated. Finally, the
      eventual identification of the target antigens detected by these antibodies may
      permit the future development of new diagnostic methods for ARM and AMD.

PMID- 15946261
TI  - Effects of 2% chlorhexidine and 5.25% sodium hypochlorite on gutta-percha cones
      studied by atomic force microscopy.
AB  - AIM: To compare the effects of 2% chlorhexidine (CHX) and 5.25% sodium
      hypochlorite (NaOCl) on gutta-percha (GP) cone structure using atomic force
      microscopy (AFM). METHODOLOGY: Two standardized GP cones were sectioned 3 mm from
      the tip, attached to a glass base and immersed in 2% CHX or 5.25% NaOCl for 1, 5,
      10, 20 and 30 min. Untreated GP cones were used as control. Topography and
      elasticity analyses were performed on 12 different regions located between 1 and
      2 mm from the tip. Root mean square (RMS) parameters for contact mode imaging and
      force modulation microscopy variations were measured. The differences between RMS
      values were tested by anova with Fisher's protected LSD test for multiple
      comparisons. RESULTS: There was no deterioration in the topography and physical
      properties studied when 2% CHX was used in comparison with the control (P <
      0.05). The RMS parameter for topography increased after 10 min of 5.25% NaOCl
      exposure in comparison with the control (P < 0.05). In addition, 5.25% NaOCl
      increased the elasticity of the GP cone after an immersion time of 1 min in
      comparison with the control (P < 0.05). CONCLUSIONS: Two per cent CHX did not
      change GP cone structure following up to 30 min exposure. Conversely, 5.25% NaOCl
      caused elastic changes after 1 min exposure.

PMID- 15946262
TI  - Influence of cervical preflaring on apical file size determination.
AB  - AIM: To investigate the influence of cervical preflaring with different
      instruments (Gates-Glidden drills, Quantec Flare series instruments and LA Axxess
      burs) on the first file that binds at working length (WL) in maxillary central
      incisors. METHODOLOGY: Forty human maxillary central incisors with complete root
      formation were used. After standard access cavities, a size 06 K-file was
      inserted into each canal until the apical foramen was reached. The WL was set 1
      mm short of the apical foramen. Group 1 received the initial apical instrument
      without previous preflaring of the cervical and middle thirds of the root canal.
      Group 2 had the cervical and middle portion of the root canals enlarged with
      Gates-Glidden drills sizes 90, 110 and 130. Group 3 had the cervical and middle
      thirds of the root canals enlarged with nickel-titanium Quantec Flare series
      instruments. Titanium-nitrite treated, stainless steel LA Axxess burs were used
      for preflaring the cervical and middle portions of root canals from group 4. Each
      canal was sized using manual K-files, starting with size 08 files with passive
      movements until the WL was reached. File sizes were increased until a binding
      sensation was felt at the WL, and the instrument size was recorded for each
      tooth. The apical region was then observed under a stereoscopic magnifier, images
      were recorded digitally and the differences between root canal and maximum file
      diameters were evaluated for each sample. RESULTS: Significant differences were
      found between experimental groups regarding anatomical diameter at the WL and the
      first file to bind in the canal (P < 0.01, 95% confidence interval). The major
      discrepancy was found when no preflaring was performed (0.151 mm average). The LA
      Axxess burs produced the smallest differences between anatomical diameter and
      first file to bind (0.016 mm average). Gates-Glidden drills and Flare instruments
      were ranked in an intermediary position, with no statistically significant
      differences between them (0.093 mm average). CONCLUSIONS: The instrument binding
      technique for determining anatomical diameter at WL is not precise. Preflaring of
      the cervical and middle thirds of the root canal improved anatomical diameter
      determination; the instrument used for preflaring played a major role in
      determining the anatomical diameter at the WL. Canals preflared with LA Axxess
      burs created a more accurate relationship between file size and anatomical
      diameter.

PMID- 15946263
TI  - The effect of the renewal of calcium hydroxide paste on the apexification and
      periapical healing of teeth with incomplete root formation.
AB  - AIM: To evaluate the influence of renewing calcium hydroxide paste on
      apexification and periapical healing of teeth in dogs with incomplete root
      formation and previously contaminated canals. METHODOLOGY: Forty premolars from
      four 6-month-old dogs were used. After access to the root canals and complete
      removal of the pulp, the canal systems remained exposed to the oral environment
      for 2 weeks. Canal preparation was then carried out using Hedstroem files, under
      irrigation with 1% sodium hypochlorite, 1 mm short of the radiographic apex.
      After drying, the canals of one premolar in each dog were left empty (group 4
      control), and those of the other nine teeth in each animal were filled with a
      calcium hydroxide-propylene glycol paste. All teeth were restored with reinforced
      zinc oxide cement (IRM) or IRM and amalgam (group 4). The paste was renewed and
      the teeth restored again 1 week later. Then, the nine teeth in each animal were
      divided into three experimental groups: group 1 - paste not changed; group 2 -
      paste renewed every 4 weeks for 5 months; and group 3 - paste renewed after 3
      months had elapsed. The teeth were restored with IRM and amalgam (groups 1 and 3)
      or IRM (group 2). The animals were killed 5 months later, and blocks of the teeth
      and surrounding tissues were submitted to histological processing. The sections
      were studied to evaluate six parameters: apical calcified tissue barrier,
      inflammatory reaction, bone and root resorption, paste extrusion and
      microorganisms. Results of experimental groups were analysed by Kruskal-Wallis
      nonparametric tests and by the test of proportions. The critical value of
      statistical significance was 5%. RESULTS: Significant differences (P < 0.05) were
      found in relation to the presence of bone resorption and paste in the
      periradicular area, the formation of a calcified tissue barrier at the apex, and
      the intensity of the apical inflammatory reaction. Bone resorption was more
      evident in group 1 (medicament not changed), and the presence of paste in the
      periodontal tissues was more common in groups 2 and 3. Renewal of the paste
      reduced the intensity of the inflammatory reaction (groups 2 and 3), but the
      formation of apical calcified tissue was more noticeable in the teeth where the
      paste had not been renewed. CONCLUSIONS: Replacement of calcium hydroxide paste
      was not necessary for apexification to occur, however, it did reduce
      significantly the intensity of the inflammatory process. Monthly renewal of
      calcium hydroxide paste reduced significantly the occurrence of apexification.

PMID- 15946264
TI  - Physico-chemical properties of MTA and a novel experimental cement.
AB  - AIM: To evaluate the release of calcium ions, pH and conductivity of a new
      experimental dental cement (EC) and to compare them with those of mineral
      trioxide aggregate (MTA-Angelus). METHODOLOGY: Five samples of each cement were
      prepared using plastic tubes 1 mm in diameter and 10 mm long. Each sample was
      sealed in a test tube containing 10 mL deionized water which was analysed after
      24, 48, 72, 96, 192, 240 and 360 h for pH, electrical conductivity and calcium
      release. The concentration of calcium ions was obtained through atomic absorption
      spectroscopy technique. The data were analysed statistically using the analysis
      of variance (anova) and the Student's test (t-test). RESULTS: The pH of the
      storage solutions was not affected by the material and the interaction of
      material with time (P > 0.05). However, the time of immersion was significant (P
      < 0.01) for both materials. For the electric conductivity and calcium release,
      the interaction of material with time was statistically significant (P < 0.01),
      indicating that EC and MTA-Angelus did not behave in a similar manner.
      CONCLUSIONS: The experimental cement released calcium and increased the pH of the
      storage solutions in a similar manner to MTA-Angelus. However, EC showed
      significantly higher calcium release than commercial MTA-Angelus after 24 h.

PMID- 15946265
TI  - Carisolv: an alternative to NaOCl in immature root canals?
AB  - AIM: To test the null hypothesis that Carisolv is no more effective than 1%
      sodium hypochlorite in cleaning uninstrumented, immature root canals.
      METHODOLOGY: A total of 240 uniform, immature ovine incisors were decoronated at
      the CEJ level and randomly divided into four groups of 60. After gross pulp
      extirpation, canals were flooded with normal saline (negative control), 1% NaOCl,
      Carisolv or 5% NaOCl (positive control) and incubated for 10 min (group 1), 20
      min (group 2), 30 min (group 3) or 30 min, refreshing irrigant at 10 and 20 min
      (group 4). SEM photomicrographs of canal wall debris in the apical, middle and
      coronal thirds were scored against a 5-point scale. Internal consistency was
      assessed by kappa statistics. Debris scores for different irrigant regimes at
      different canal levels were analysed by non-parametric tests (P < 0.05). RESULTS:
      Canals were consistently cleaner in the coronal and middle than apical thirds.
      NaOCl (5%) was consistently most effective. Carisolv and NaOCl (1%) were no more
      effective than normal saline in group 1 (P > 0.05), but significantly more
      effective than normal saline in groups 2 (middle and apical 1/3), 3 and 4 (P <
      0.05). Carisolv and NaOCl (1%) had comparable activity in groups 1, 2 (middle and
      apical thirds) and 3, but NaOCl (1%) was significantly more effective than
      Carisolv in group 4 (coronal and middle thirds). CONCLUSIONS: 1. The ovine
      incisor model presents opportunities to investigate irrigation regimes under
      controlled ex-vivo conditions. 2.NaOCl (5%) remains the most effective irrigant
      for rapid debris removal in immature root canals. 3. Carisolv cleans pulp debris
      from the walls of immature root canals as effectively as NaOCl (1%) during
      static, unrefreshed wall contact for between 20 and 30 min. 4. Refreshment of
      NaOCl (1%) enhances its cleaning ability above that of Carisolv.

PMID- 15946266
TI  - Root canal preparation with Endo-Eze AET: changes in root canal shape assessed by
      micro-computed tomography.
AB  - AIM: To evaluate the relative performance of Endo-Eze Anatomic Endodontic
      Technology (AET) stainless steel instruments when shaping maxillary molar root
      canals in vitro. Methodology Extracted human maxillary molars were scanned,
      before and after root canal shaping with Endo-Eze AET, employing micro-computed
      tomography (muCT) at an isotropic resolution of 34 microm. Three-dimensional root
      canal models were reconstructed and evaluated for volume, surface area,
      'thickness' (diameter), canal transportation and prepared surface. Preparation
      errors such as apical zips, perforations and fractured instruments were visually
      determined from those models. Means were contrasted using anova and Scheffe post
      hoc tests. RESULTS: Volume and surface area increased significantly and similarly
      in mesiobuccal (mb), distobuccal (db) and palatal (p) canals and gross
      preparation errors (n = 17) were found. Mean root canal diameters, 5 mm coronal
      to the apex, increased from 0.31 to 0.52, 0.35 to 0.50 and 0.50 to 0.70 mm for
      mb, db and p canals, respectively. Mean canal transportation ranged from 0.15 to
      0.29, 0.15 to 0.27 and 0.21 to 0.33 mm for apical, middle and coronal root canal
      levels, respectively, with highest values found for mb canals (P < 0.003). Root
      canals were significantly straightened during preparation (P < 0.002).
      CONCLUSIONS: In summary, Endo-Eze AET instruments shaped root canals in maxillary
      molars with substantial canal transportation, particularly in mesiobuccal root
      canals. Preparation with this instrument removed high volumes of dentine, even
      though apical preparation was size 30. Based on the current results, Endo-Eze AET
      cannot be recommended for the preparation of teeth with curved root canals.

PMID- 15946267
TI  - Apoptosis in epithelial cells of apical radicular cysts.
AB  - AIM: To investigate the occurrence of apoptotic cell death in the epithelium of
      radicular cysts and to compare its frequency in lesions presenting a distinct
      functional state. METHODOLOGY: Twenty radicular cysts were selected and arranged
      into two groups with 10 lesions in each group: atrophic (quiescent) and
      hyperplastic (active) epithelium. Morphologic investigations of apoptosis were
      conducted by means of optic microscopy in haematoxylin and eosin slides.
      Immunohistochemical techniques to detect the bcl-2 protein were carried out by
      streptavidin-biotin-peroxidase assay. In both instances, 30 sequential high-power
      microscopic fields were observed to determine apoptotic (AI) and bcl-2
      immunostaining (bcl-2I) indexes. The presence of AI and bcl-2I within the two
      groups was compared using the t-test. Correlation between the AI and the bcl-2I
      was investigated using the Spearman test. RESULTS: Apoptosis was detected in the
      epithelium of all cysts. Higher AI levels were found in lesions with an atrophic
      (0.17 +/- 0.19) rather than a hyperplastic (0.10 +/- 0.10) epithelium. The same
      was found for the bcl-2I levels (0.06 +/- 0.03 vs. 0.04 +/- 0.01, respectively).
      However, these differences were not statistically significant. A positive and
      significant correlation was found between AI and bcl-2I. CONCLUSIONS: Apoptosis
      was always present in the epithelium of the lesions and was more frequent in
      lesions with atrophic (quiescent) epithelium.

PMID- 15946268
TI  - An assessment of endodontic re-treatment decision-making in an educational
      setting.
AB  - AIM: To test the applicability of Praxis Concept (PC) theory in endodontic re
      treatment decision-making amongst dental students of similar backgrounds, but
      from two dental schools. METHODOLOGY: A total of 172 students from two dental
      schools (n = 97 and n = 75) were asked to select their management choices (from
      five possible options) for each of six variations on quality (by way of adequacy
      of root filling) and complexity (by way of absence or presence of a post) of a
      simulated radiograph of an anterior tooth. The six variations each had five
      possible levels of periapical condition, giving a total of 30 cases for which
      management choices were sought. Individual re-treatment preference scores (RPS)
      were obtained, from which school and gender differences were compared by t-test.
      The association between students' stated re-treatment propensities and the
      different cases was expressed as odds ratios using unconditional logistic
      regression analysis. RESULTS: There were large inter-individual variations in RPS
      within the cases at both schools. Mean RPS for the group was 0.62 (SD 0.14), and
      did not differ between the schools (P = 0.44), but was significantly lower for
      males than females (P = 0.01). For all participants and a given case, if re
      treatment was proposed for a particular size of lesion, then all larger lesions
      for that case were also marked for re-treatment. Presence of a defective root
      filling or overfilling reflected a greater propensity for re-treatment than when
      the root filling was adequate, whilst the absence/presence of a post had no clear
      effect on re-treatment choices. CONCLUSIONS: The findings support the explanatory
      potential of PC theory in endodontic re-treatment decision-making in the group
      investigated, and suggest that factors besides disease status alone, may
      contribute to the choices that clinicians make.

PMID- 15946269
TI  - Methods of experimental induction of periapical inflammation. Microbiological and
      radiographic evaluation.
AB  - AIM: To evaluate the influence of coronal filling and apical perforation on the
      induction of periapical inflammation. METHODOLOGY: Fifty-eight root canals in the
      teeth of dogs were divided into four groups. Groups I and II: root canals were
      exposed for 180 days; groups III and IV: root canals were exposed for 7 days and
      then the access cavity filled for 53 days. The root apices of groups I and III
      were perforated after the coronal opening, whilst those of groups II and IV
      remained intact. Standard radiographs were taken before and after the
      experimental periods. Digital images of the radiographs were created and then
      analysed by three examiners. After induction of periapical inflammation, the root
      canal contents were collected using paper points. Microbiologic evaluation of the
      type of microorganism was carried out by culture in different growth media. The
      radiographic and microbiologic data were statistically analysed using anova at a
      5% significance level. RESULTS: There were a greater total number of
      microorganisms in groups I and II (P < 0.05). The number of anaerobes was greater
      than the number of aerobes (P < 0.05). The size of the periapical radiolucencies
      were not significantly different between the experimental groups. CONCLUSIONS:
      The different methods analysed induced similar areas of periapical radiolucency
      in dogs with predominantly anaerobic bacteria. However, the time required for
      induction was less when the method with coronal filling was used.

PMID- 15946270
TI  - Short-term antibacterial activity of root canal sealers towards Enterococcus
      faecalis.
AB  - AIM: To investigate the antimicrobial activity of root canal sealers on
      Enterococcus faecalis, either allowing or avoiding direct contact between sealers
      and bacteria. METHODOLOGY: Filter paper discs were immersed in standardized E.
      faecalis suspensions and exposed to freshly mixed sealers (MCS, AH Plus,
      Grossman's sealer, Sealapex, Apexit) in teflon wells for 30 min, with or without
      a filter membrane placed between filter paper discs and sealers (membrane
      restricted contact test and direct contact test, respectively). After exposure,
      the filter paper discs were transferred to vials containing phosphate-buffered
      saline (PBS) and glass beads, and vigorously vortexed. PBS with resuspended
      bacterial cells was serially diluted and 25 microL droplets were seeded on TSA
      plates. The plates were incubated in air at 37 degrees C for 24 h and colony
      forming units were counted. Using alpha = 0.05 as level for statistical
      significance, the data obtained were analysed using Student's t-test. RESULTS: In
      the direct contact test, MCS and AH Plus killed the bacteria to a level below the
      detection limit. They were followed in decreasing order of efficacy by Grossman's
      sealer, Sealapex and Apexit. In the membrane-restricted contact test, the sealers
      ranked: MCS, AH Plus, Grossman's sealer, Apexit and Sealapex, in descending order
      of antibacterial potency. MCS, AH Plus and Grossman's sealer significantly
      reduced the number of viable bacteria in both tests. Sealapex and Apexit were not
      statistically different from control. CONCLUSIONS: MCS, AH Plus and Grossman's
      sealer were effective in reducing the number of cultivable cells of E. faecalis.
      Calcium hydroxide-based sealers, Sealapex and Apexit were ineffective in this
      short-term experiment.

PMID- 15946271
TI  - Continued root formation of a pulpless permanent incisor following root canal
      treatment: a case report.
AB  - AIM: To present a case of a pulpless permanent incisor that continued root
      formation following root canal treatment. SUMMARY: A healthy 8-year-old girl with
      a history of dental trauma resulting in a coronal fracture involving enamel,
      dentine and pulp was referred by her general dental practitioner for treatment
      and evaluation of tooth 21. The tooth had a necrotic pulp and periapical
      rarefaction was evident radiographically. The canal was prepared, dressed with
      Ca(OH)2 and then filled with a rolled gutta percha cone and Roth's root canal
      sealer. A radiograph exposed eight years post-treatment, showed evidence of
      continued apical formation. KEY LEARNING POINTS: *Teeth with necrotic pulps and
      periapical rarefaction may show evidence of continued apical formation after root
      canal treatment. *Hertwig's epithelial root sheath may be more resistant than
      expected to trauma and infection.

PMID- 15946272
TI  - Improving research career opportunities for clinical nurses in the UK.

PMID- 15946273
TI  - Short profile: Kate Wilson.

PMID- 15946274
TI  - Clinical education facilitators: a literature review.
AB  - AIMS AND OBJECTIVES: The aim of this literature review, set within an Irish
      context, is to present a broad overview of former and existing clinical support
      personnel, explore the concept of facilitation and examine what is known about
      the role of the clinical education facilitator. BACKGROUND: The importance of
      providing a supportive clinical environment to enhance clinical teaching and
      learning is strongly portrayed in the literature. While the past two decades have
      borne witness to various clinical support personnel, the literature identifies
      conflicting demands that these personnel face. No suggestions are advanced as to
      how to overcome these difficulties, which inevitably influence the quality and
      quantity of their clinical teaching role. An identifiable gap exists over who has
      prime responsibility for clinical teaching. It is timely that alternative
      possibilities for organizing clinical teaching are investigated. A new post
      emerging in practice settings is that of the clinical education facilitator who
      is meant to be the key linchpin in clinical areas for reducing the theory
      practice gap. METHOD: Relevant literature for this review was sourced using the
      computerized databases CINAHL, Medline and Synergy. Manual searching of relevant
      nursing journals and sourcing of secondary references extended the search.
      Government reports and other relevant documents were obtained through pertinent
      websites. RESULTS: Papers that explicitly examined the concept of facilitation
      and explored the posts of clinical education facilitators were included; six
      research papers were accessed and reviewed. In addition seven non-empirical
      papers were included. CONCLUSIONS: It is clear that considerable lack of role
      clarity resides over what constitutes clinical facilitation and the role of the
      clinical facilitator. Thus, it is paramount to strengthen this support role with
      Irish empirical evidence. RELEVANCE TO CLINICAL PRACTICE: A major advantage in
      having a ward-based clinical education facilitator is the benefit of having
      access to someone who can concentrate solely on clinical education and support
      with attempts to narrow the theory-practice divide.

PMID- 15946275
TI  - Assessment of nursing management and utilization of nursing resources with the
      RAFAELA patient classification system--case study from the general wards of one
      central hospital.
AB  - BACKGROUND: RAFAELA is a new Finnish PCS, which is used in several University
      Hospitals and Central Hospitals and has aroused considerable interest in
      hospitals in Europe. AIMS AND OBJECTIVES: The aim of the research is firstly to
      assess the feasibility of the RAFAELA Patient Classification System (PCS) in
      nursing staff management and, secondly, whether it can be seen as the
      transferring of nursing resources between wards according to the information
      received from nursing care intensity classification. METHODS: The material was
      received from the Central Hospital's 12 general wards between 2000 and 2001. The
      RAFAELA PCS consists of three different measures: a system measuring patient care
      intensity, a system recording daily nursing resources, and a system measuring the
      optimal nursing care intensity/nurse situation. The data were analysed in
      proportion to the labour costs of nursing work and, from that, we calculated the
      employer's loss (a situation below the optimal level) and savings (a situation
      above the optimal level) per ward as both costs and the number of nurses.
      RESULTS: In 2000 the wards had on average 77 days below the optimal level and 106
      days above it. In 2001 the wards had on average 71 days below the optimal level
      and 129 above it. Converting all these days to monetary and personnel resources
      the employer lost 307,745 or 9.84 nurses and saved 369,080 or 11.80 nurses in
      total in 2000. In 2001 the employer lost in total 242,143 or 7.58 nurses and
      saved 457,615 or 14.32 nurses. During the time period of the research nursing
      resources seemed not have been transferred between wards. CONCLUSIONS: RAFAELA
      PCS is applicable to the allocation of nursing resources but its possibilities
      have not been entirely used in the researched hospital. The management of nursing
      work should actively use the information received in nursing care intensity
      classification and plan and implement the transferring of nursing resources in
      order to ensure the quality of patient care. RELEVANCE TO CLINICAL PRACTICE:
      Information on which units resources should be allocated to is needed in the
      planning of staff resources of the whole hospital. More resources do not solve
      the managerial problem of the right allocation of resources. If resources are
      placed wrongly, the problems of daily staff management and cost control continue.

PMID- 15946276
TI  - Finnish nurses' and nursing students' pharmacological skills.
AB  - PURPOSES AND OBJECTIVES: The purposes of this study were to investigate the
      pharmacological skills of Finnish nurses and graduating nursing students, to
      determine how pharmacological skills are related to background factors and to
      identify differences between nurses and students and, finally, to examine how the
      instrument used, the Medication Calculation Skills Test, works. BACKGROUND:
      Pharmacology is a relevant and topical subject. In several studies, however,
      pharmacological skills of nurses and nursing students have been found
      insufficient. In addition, pharmacology as a subject is found to be difficult for
      both nursing students and nurses. DESIGN AND METHODS: The study was evaluative in
      nature; the data were collected using the Medication Calculation Skills Test,
      developed for the purposes of this study. The instrument was used to gather
      information on background factors and self-rated pharmacological and mathematical
      skills and to test actual skills in these areas. RESULTS: Results concerning
      pharmacological skills are reported in this paper. The maximum Medication
      Calculation Skills Test score was 24 points. The mean score for nurses was 18.6
      and that for students 16.3. Half of (50%) the students attained a score of 67%
      and 57% of nurses attained a score of 79%. CONCLUSIONS: Nurses and students had
      some deficiencies in their pharmacological skills. Nurses had better
      pharmacological skills than students according to both self-ratings and actual
      performance on the test. RELEVANCE TO CLINICAL PRACTICE: It is vitally important
      that nurses have adequate pharmacological skills to administer medicines
      correctly. This study showed that the Medication Calculation Skills Test seems to
      work well in measuring pharmacological skills, even though it needs further
      evaluation. Findings from this study can be used when planning the nursing
      curriculum and further education for Registered Nurses.

PMID- 15946277
TI  - Admiral nursing competency project: practice development and action research.
AB  - AIMS AND BACKGROUND: Admiral Nurses are specialist dementia care nurses working
      in the community with carers of those who have a dementia. The aim of the
      competency project (2000-2003) was threefold. Firstly to work collaboratively
      with these specialist nurses to facilitate the development a competency framework
      that reflects the needs of the Admiral Nursing Service. Secondly, to provide a
      way to structure evidence demonstrating evolving competency. Thirdly, to
      specifically enable the nurses to demonstrate evidence of achieving the UK
      Nursing and Midwifery Council's Higher Level Practice standard. DESIGN AND
      METHODS: The two complementary approaches of emancipatory action research and
      systematic practice development were adopted. Methods were taken from action
      research and systematic practice development approaches with an emphasis on
      promoting and enabling enlightenment, critical reflection, ownership and creating
      the best conditions for long-term commitment to the competency framework.
      RESULTS: The main outcome from this project was the development of a specialist
      nursing competency framework. The Admiral Nurses' Competency Framework is made up
      of a set of eight core competencies with three levels of competency statements,
      loosely structured around the Higher Level Practice standard, and guidance
      documentation to illustrate how work-based evidence can be generated to
      demonstrate competence. There were also process-derived outcomes associated with
      combining systematic practice development with emancipatory action research that
      had an impact on the culture. The main outcomes here were that practitioners
      engaged in and experienced learning about how to research their own practice and
      the consequences of doing this. They also learnt about specialist nursing
      practice more widely than Admiral Nursing. Finally, there was some increase in
      awareness about the culture within their teams and organizations. The final
      competency framework reflects the needs of the service, is owned by the majority
      of practitioners and project commissioners and this has had a positive impact on
      implementation. CONCLUSION: In this paper, we report on combining systematic
      practice development with action research to achieve immediate project aims. In
      addition we show how a project of this nature can contribute to developing skills
      in practitioners necessary for cultural changes in practice and contributes to
      wider issues of modernization within nursing and health care. RELEVANCE TO
      CLINICAL PRACTICE: This competency framework will enable Admiral Nurses to
      demonstrate their level of specialist practice, as individuals and collectively
      as a service and it also promotes the principles of nurses as life long learners.
      This may have relevance to other groups of specialist nurses. The project has
      widespread relevance for two reasons. Firstly, it shows that nurses can be
      involved in designing and testing a competency framework as collaborators.
      Secondly, that to achieve this within the spirit of approaches, such as
      systematic practice development and action research, can be testing for all
      collaborators even were there is a shared or espoused aim.

PMID- 15946278
TI  - Exploration of patients' needs for information on arrival at a geriatric and
      rehabilitation unit.
AB  - AIM: The aim of this study was to gather information about patients' needs prior
      to transferring from an acute care facility to a rehabilitation setting that
      could assist patients to engage actively in rehabilitation activities upon
      entering the unit. BACKGROUND: The provision of information is an important
      aspect of health care as it assists patients to become informed and actively
      participate in this care. Improved recovery has been associated with patients'
      adherence to care regimes. METHOD: Semi-structured interviews were undertaken
      with a convenient sample of nine patients shortly after admission/transfer to a
      rehabilitation unit and with four of these patients after discharge. The intent
      was to learn what information patients receive prior to admission to the
      rehabilitation unit, whether this information is useful and whether different
      information would be more useful to facilitate patients' engagement in the
      activities central to rehabilitation treatment. RESULTS: Interviews revealed
      that, generally, patients received very little information about what to expect
      on admission to the rehabilitation unit and patients' engagement was more
      dependent on perceptions about rehabilitation. Thematic analysis identified that,
      in general, rehabilitation was perceived as 'a ticket out' and 'a good thing'. In
      relation to provision of information of participants identified that 'doesn't
      matter that I don't know'; 'information is not always meaningful' and 'I will
      adjust in my own time'. RELEVANCE TO CLINICAL PRACTICE: Health professionals need
      to recognize that patients are often compliant with decisions made while they are
      inpatients of the current health care system. Even though patients may 'actively
      participate' in rehabilitation processes it is often still as a passive recipient
      of health care.

PMID- 15946279
TI  - Care needs of residents in community-based long-term care facilities in Taiwan.
AB  - AIM: The purpose of this study is to gain an understanding both of the
      characteristics of residents who receive the services of nursing assistants and
      the service intensity (service tasks, service time and cost) of nursing
      assistants as a means of developing a patient classification based upon resource
      consumption. BACKGROUND: Most people in Taiwan send their disabled older family
      members to community-based long-term care facilities instead of nursing homes
      because they are much cheaper, and because they are generally closer to their
      homes, making visits more convenient. Nursing assistants make up the largest
      group of personnel in long-term care facilities. To determine resource use, both
      the service time and the actual activities performed for a resident by nursing
      assistants need to be assessed and this will help to develop a patient
      classification system to predict resource use and patient outcomes. METHODS: A
      descriptive survey method was used to identify the tasks performed by nursing
      assistants in community-based long-term care facilities in Taiwan. Nursing
      assistants were recruited from 10 long-term care facilities in the Shihlin and
      Peitou Districts of Taipei City. Thirty-four nursing assistants and 112 residents
      participated in this study. RESULTS: Findings showed that each nursing assistant
      spent 5.05 hours per day doing direct service care, which is much higher than the
      2.08 hours for nursing assistants in the United States. Among service tasks
      provided by nursing assistants, personal care consumed 35.1% of their time. Non
      complex treatments were second (33.3%). Skilled nursing and medical services were
      third (31.6%). The service intensity required of nursing assistants was strongly
      related to the residents' activities of daily living and their needs. CONCLUSION:
      Complex nursing procedures are normally provided by Registered Nurses in nursing
      homes and consumed almost as much of the nursing assistants' time as did personal
      care activities in this study. RELEVANCE TO CLINICAL PRACTICE: It is suggested
      that a training program for nursing assistants, especially for foreigners in
      community-based long-term care facilities, should be mandated to assure the
      quality of service.

PMID- 15946280
TI  - Hip fracture: family caregivers' burden and related factors for older people in
      Taiwan.
AB  - AIMS: The purpose of this study was to explore the burden experienced by
      caregivers during the transition from hospital to home. BACKGROUND: With a
      growing older population, home-based care has gradually gained more recognition.
      Most older people with hip fracture in Taiwan have to be discharged at a
      relatively early stage. Therefore, the caregiving tasks falls on the families.
      METHODS: A total of 98 older people with hip fracture and their caregivers were
      interviewed. The sample was selected from three medical centres in Taipei, and
      questionnaires were collected at one week and one month following hospital
      discharge. RESULTS: (i) Family caregivers were usually women (63.3%) with spouses
      being the primary caregivers in most cases (30.6%). About one-third of caregivers
      took care of other family members on top of their responsibilities caring for the
      sick elders at home, and 77.6% shared the care tasks with others. (ii) The
      caregivers experienced moderate burdens. About 91.8% of caregivers reported 'I
      feel sad watching the elder's health deteriorating', 84.9% reported 'I must keep
      an eye on the elder constantly' and 56.7% reported 'Taking care of the sick elder
      at home makes me feel exhausted'. (iii) Caregiver burden and the functional level
      of older people were adversely correlated. (iv) Caregivers who were unable to
      access other resources for help and/or had provided care to the older person
      prior to the fracture resulting in hospitalization experienced a higher burden.
      CONCLUSIONS: These findings should be helpful in the formulation of evidence
      based discharge planning and home health care services. RELEVANCE TO CLINICAL
      PRACTICE: Comprehensive discharge planning and developing social support systems
      for family caregivers to reduce caregivers burden are needed.

PMID- 15946281
TI  - Becoming an advanced practitioner in neonatal nursing: a psycho-social study of
      the relationship between educational preparation and role development.
AB  - AIMS AND OBJECTIVES: The aims of this research were to identify (a) the
      educational and working experiences and (b) subsequent training needs of
      graduates of one ANNP course in the UK. The objectives were (a) to assess the
      medium to long-term impact of the training programme on the professional
      development of the respondents; (b) identify potential areas of excellence and
      (c) areas for improvement in this and other training programmes for ANNPs.
      BACKGROUND: Neonatal intensive care continues to be a rapidly changing area of
      work. Nurses and doctors in neonatal intensive care units (NICUs) have to be
      skilled equally in interpersonal communications and technical expertise. The
      Advanced Neonatal Nurse Practitioner (ANNP) training programme was introduced in
      1992 in the UK in the broader political context of extending nursing roles in a
      range of specialties. The role of the neonatal intensive care nurse had expanded
      elsewhere previously, particularly in North America as a response to medical
      staffing crises where the practice and the training/education programmes were
      expanded during the 1970s/1980s and continued to evolve to encompass an advanced
      role for the neonatal nurse practitioner. DESIGN: This was a study of five
      cohorts of graduates from one university course training programme for advanced
      neonatal practitioners (ANNPs) to explore their experiences of their role as
      ANNPs in the context of changes and developments in the British National Health
      Service and their own personal and professional development. METHODS: This study
      employs mixed methods (interviews, focus groups and a survey) and forms of data
      analysis (qualitative and quantitative) to explore the experiences of the
      transition to becoming an advanced practitioner. Data were collected from a
      sample of five cohorts; members of the current course team and the nursing and
      medical staff at one NICU which employs many of these graduates. RESULTS: Most
      graduates value their course experience and the ANNP role and the findings
      suggest that confidence about practice develops naturally with postcourse
      experience. However, the more experienced and confident ANNPs frequently reported
      increased inter-professional role confusion/conflict with junior doctors, and
      some consultants particularly where there are only one or two ANNPs overall in
      the team. CONCLUSIONS: There are personal and professional benefits to individual
      nurses who have had this training. However more attention needs to be paid to
      ongoing professional development particularly the management of professional role
      relationships among all nurses and between nurses and doctors. RELEVANCE TO
      CLINICAL PRACTICE: A focus on professional role relationships and more effective
      communication in the clinical setting would be of benefit to all members of multi
      disciplinary teams. A greater level of day-to-day support is required for ANNPs,
      other neonatal nurses and junior doctors if this is to be achieved, especially in
      clinical settings where there are few ANNPs or the addition of these clinical
      specialists is relatively new.

PMID- 15946282
TI  - Asthma--quality of life for Swedish children.
AB  - AIMS AND OBJECTIVES: The purpose of this study was to describe how Swedish
      children with asthma experience their QoL and to search for possible associations
      between their experience of QoL and some determinants. BACKGROUND: Asthma is a
      chronic disorder that can restrict a child's life, physically, emotionally,
      socially and spiritually, and this has an impact on a child's quality of life
      (QoL). METHODS: Two hundred and twenty-six children with asthma (37% girls and
      63% boys) and 371 parents of these children participated in the study. The
      Paediatric Asthma Quality Of Life Questionnaire (PAQLQ) was used to measure the
      children's QoL. This questionnaire reveals how the children's asthma interferes
      with their normal activities, their symptoms and how this interference has made
      them feel. RESULTS: The findings show that most children with asthma estimated
      their QoL towards the positive end of the scale. The children reported more
      impairment in the domain of activities than in emotions and symptoms. The most
      commonly restricted activity was the children's ability to run. Significant
      associations were found between a higher QoL outcome and being a boy, as well as
      living in the south of Sweden. A higher QoL was also found in children with
      mothers older than 40 years of age and in children with cohabiting parents. It
      was also associated with their fathers' QoL in a positive direction. CONCLUSIONS:
      It is important that children with asthma will maintain a high QoL. In this study
      the children were being treated with asthma medication when they evaluated their
      QoL. Perhaps this fact might have influenced the results in a positive direction.
      RELEVANCE TO CLINICAL PRACTICE: The findings of our study underline the
      importance of accurate nursing assessment including background variables of the
      children. Nurses also have to be aware that some of the children in the study
      have a low QoL and these children must not be forgotten. In addition, as caring
      tends to focus on the patients' limitations, another important issue for nurses
      is to try to discover those aspects in a child's daily life that contribute to a
      high QoL in order to improve and maintain the child's wellbeing.

PMID- 15946283
TI  - Comparison of plain ice and flavoured ice for preventing oral mucositis
      associated with the use of 5 fluorouracil.
AB  - AIMS AND OBJECTIVES: The study aimed to compare the use of plain ice, flavoured
      ice and standard care, to evaluate the effect on mucositis and to determine
      patients' perceptions of the two forms of oral cryotherapy. BACKGROUND: Despite
      evidence that oral cryotherapy is useful in preventing mucositis in patients
      receiving 5-fluorouracil, concerns have been expressed about its clinical
      utility, due to potential side effects and negative perceptions. DESIGN: A
      randomized, controlled, crossover trial was conducted in the outpatient
      chemotherapy department of an acute care teaching hospital in Perth, Western
      Australia. Patients were randomized to receive each of three interventions across
      three cycles of chemotherapy: standard care alone; standard care plus plain ice;
      and standard care plus flavoured ice. METHODS: Oral mucositis was assessed by
      nurses prior to each of the three chemotherapy cycles and 15 days after each
      intervention. Two assessment tools were used, the Oral Assessment Guide, and the
      Western Consortium Cancer Nursing Research Scale. Participants completed a
      questionnaire to determine their comfort and satisfaction with oral cryotherapy,
      as well as factors affecting compliance. RESULTS: Findings from 67 patients
      revealed that when participants used standard care alone, they were significantly
      more likely to experience symptoms of mucositis than when they used either plain
      or flavoured ice. Odds ratios were at least threefold higher for standard care
      alone, varying according to the instrument used. The two main concerns reported
      were the taste of flavoured ice and the time required to complete the cryotherapy
      interventions. Side effects such as nausea, sensitivity and headache were
      reported more frequently for flavoured ice (n = 11) compared with plain ice (n =
      5) and standard care (n = 1). CONCLUSIONS: Both forms of oral cryotherapy were
      effective in reducing the severity of oral mucositis after chemotherapy and were
      more effective than standard care alone. Flavoured ice was associated with the
      highest frequency of side effects. RELEVANCE TO CLINICAL PRACTICE: The benefits
      of cryotherapy appear to outweigh the problems in this sample of patients. The
      intervention should be tailored to individual patients, based on preferences for
      plain versus flavoured ice and small chips vs. larger blocks. Unsweetened frozen
      fruit juices should be evaluated. Time constraints could be addressed by
      providing transportable containers of ice.

PMID- 15946284
TI  - Chemotherapy: the effect of oral cryotherapy on the development of mucositis.
AB  - AIMS AND OBJECTIVE: The aim of this study is to investigate the effect of oral
      cryotherapy on the development of chemotherapy-induced mucositis in patients
      administered combined chemotherapy. BACKGROUND: Mucositis has been of interest to
      scientists for more than 20 years. Unfortunately, this has not resulted in the
      development of standard procedures for prevention and management. To cope with
      this side-effect and to prevent opportunistic infections that may emerge during
      treatment, attempts are taken to provide preventative and comfort measures. In
      this context, cryotherapy (oral cooling) has become popular as a cheap and
      readily applicable method in preventing the developing due the rapid infusion of
      chemotherapy agents, or decreasing its severity. DESIGN AND METHOD: Study
      involved 60 patients, 30 of whom were in the study group and 30 in the control
      group. Ice cubes at a size that can be moved easily in the mouth and whose
      corners have been smoothed in order that they will not cause irritation in the
      mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was
      initiated five minutes before chemotherapy and maintained during venous infusions
      of etoposide (Vepesid), platinol (Cisplatin), mitomycin (Mitomycin-C) and
      vinblastin (Velbe) depending on the chemotherapy course. RESULTS: According to
      Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group
      and 90.0% in control group, the difference between two groups being statistically
      significant (P < 0.05). According to Physician-Judged Mucositis Grading, the rate
      of mucositis is 10.0% in the study group and 50.0% in the control group, the
      difference between two groups being statistically significant (P < 0.05). Oral pH
      values decreased in 90% of the subjects in study group, i.e. mucositis risk was
      reduced whereas oral pH values remained unchanged or decreased in 86.7% of the
      subjects in the control group, namely mucositis risk increased. The difference
      between study and control groups in terms of the change in pH values after
      chemotherapy was found to be statistically significant (P < 0.05). CONCLUSION:
      Our findings have demonstrated that oral cryotherapy makes an important
      contribution to the protection of oral health by reducing the mucositis score
      according to patient- and physician-judged mucositis score and by increasing oral
      pH values. RELEVANCE TO CLINICAL PRACTICE: Aggressive cancer therapy places
      patients at greater risk for oral complications and treatment-related
      consequences. Unfortunately, prevention and/or treatment of such oral sequelae
      have often become overlooked as priorities of the treatment team. Effective
      approaches for the prevention or treatment of oral mucositis have not been
      standardized, and vary considerably among institutions. Prophylactic measures
      begin with an increased emphasis on improved oral status. Oral cryotherapy, the
      therapeutic administration of cold, is a prophylactic measure for oral
      inflammation. The relevance for clinical practice will be to understand the
      content of mucositis; comprehensive care should focus on the prevention of this
      complication in the clinical practice.

PMID- 15946285
TI  - The impact of an ICU liaison nurse: a case study of ward nurses' perceptions.
AB  - AIMS AND OBJECTIVES: To provide a description of ward nurses perceptions of the
      intensive care unit liaison nurse role. BACKGROUND: Critical care outreach
      services have become commonplace over recent years. In Australia, the intensive
      care unit liaison nurse, developed at a local level by healthcare providers, has
      emerged as a way of improving the continuity of care offered to this patient
      group. As a relatively new development in critical care services, evaluation of
      this role has been limited, particularly in relation to the perceptions of ward
      nurses who receive patients on discharge from intensive care unit. DESIGN: Case
      study of one Australian hospital that utilizes an intensive care unit liaison
      nurse. METHODS: Ten ward nurses were purposefully selected for their
      representativeness of the population and for their experience with the intensive
      care unit liaison nurse role. Each of these nurses participated in semi
      structured in-depth interviews. Thematic analysis was used to analyse the data.
      FINDINGS: Three major themes emerged from the interviews, highlighting role
      behaviours, contextual demands and outcomes associated with the intensive care
      unit liaison nurse role. The role behaviours of the liaison nurse included the
      professional characteristics of the individual and the primacy of clinical
      liaison as a role descriptor. Contextual demands were environmental
      characteristics relevant to providing patient, family and staff support. Outcomes
      of the role were perceived to include environmental preparation and education.
      CONCLUSIONS: This qualitative study has presented an overview of ward nurses
      perceptions of the intensive care unit liaison nurse role within one Australian
      hospital, illustrating the educative and empathic support that the liaison nurse
      role can provide to ward nurses. RELEVANCE TO CLINICAL PRACTICE: Collaboration
      with ward nurses in developing specialist roles such as the intensive care unit
      liaison nurse is essential in ensuring improvements in patient and family care
      across the continuum.

PMID- 15946286
TI  - From the emergency department to home.
AB  - AIM: The purpose of this study was to explore dimensions of the management of the
      older person following care in an emergency department in preparation for
      discharge home by identifying perceptions and attitudes of staff in both
      emergency department and primary care sectors. BACKGROUND: It is recognized that
      older people discharged home directly from the emergency department are a
      vulnerable group. Effective communication and liaison are seen to be keys to the
      provision of high quality care for older people in the emergency department and
      in ensuring a seamless care between sectors. DESIGN: A purposeful sample was
      collected that comprised the total population (n = 222) of all grades of medical
      and nursing staff in both the emergency department and all nursing (Public Health
      Nurses & Practice nurses) and medical staff (General Practitioners) in the
      primary care area. METHODS: Methodology used was that of a survey approach of
      nursing and medical staff in both the emergency department and primary care
      services. Standardized questionnaires were employed which comprised both open and
      closed questioning style. Raw statistical data were analysed using SPSS for
      Windows while the qualitative data arising from the open-ended questions were
      content analysed for themes. RESULTS: Many staff in the primary care area
      reported the level of communication between the emergency department and the
      primary care area as unsatisfactory with confusion regarding follow-up care and a
      lack of support for older people on discharge. Hospital staff reported the level
      of communication to be much greater than that perceived by their colleagues in
      primary care. There was agreement of staff in both sectors in relation to the
      perceived usefulness of a discharge liaison nurse in the emergency department.
      CONCLUSIONS: Previous research highlights communication difficulties when
      patients are discharged from hospital. Findings from this study indicate that
      this problem can also be applied to the emergency department. RELEVANCE TO
      CLINICAL PRACTICE: Implications for practice include a need for a
      multidisciplinary approach to developing referral guidelines, staff training and
      a comprehensive dissemination of information between sectors ultimately to
      improve quality and continuity of care for the older person.

PMID- 15946288
TI  - Bioaugmentation for bioremediation: the challenge of strain selection.
AB  - Despite its long-term use in bioremediation, bioaugmentation of contaminated
      sites with microbial cells continues to be a source of controversy within
      environmental microbiology. This largely results from its notoriously unreliable
      performance record. In this article, we argue that the unpredictable nature of
      the approach comes from the initial strain selection step. Up until now, this has
      been dictated by the search for catabolically competent microorganisms, with
      little or no consideration given to other essential features that are required to
      be functionally active and persistent in target habitats. We describe how
      technical advances in molecular biology and analytical chemistry, now enable
      assessments of the functional diversity and spatial distribution of microbial
      communities to be made in situ. These advances now enable microbial populations,
      targeted for exploitation, to be differentiated to the cell level, an advance
      that is bound to improve microbial selection and exploitation. We argue that this
      information-based approach is already proving to be more effective than the
      traditional 'black-box' approach of strain selection. The future perspectives and
      opportunities for improving selection of effective microbial strains for
      bioaugmentation are also discussed.

PMID- 15946289
TI  - Niche heterogeneity determines bacterial community structure in the termite gut
      (Reticulitermes santonensis).
AB  - Differences in microenvironment and interactions of microorganisms within and
      across habitat boundaries should influence structure and diversity of the
      microbial communities within an ecosystem. We tested this hypothesis using the
      well characterized gut tract of the European subterranean termite Reticulitermes
      santonensis as a model. By cloning and sequencing analysis and molecular
      fingerprinting (terminal restriction fragment length polymorphism), we
      characterized the bacterial microbiota in the major intestinal habitats - the
      midgut, the wall of the hindgut paunch, the hindgut fluid and the intestinal
      protozoa. The bacterial community was very diverse (> 200 ribotypes) and
      comprised representatives of several phyla, including Firmicutes (mainly
      clostridia, streptococci and Mycoplasmatales-related clones), Bacteroidetes,
      Spirochaetes and a number of Proteobacteria, all of which were unevenly
      distributed among the four habitats. The largest group of clones fell into the so
      called Termite group 1 (TG-1) phylum, which has no cultivated representatives.
      The majority of the TG-1 clones were associated with the protozoa and formed two
      phylogenetically distinct clusters, which consisted exclusively of clones
      previously retrieved from the gut of this and other Reticulitermes species. Also
      the other clones represented lineages of microorganisms that were exclusively
      recovered from the intestinal tract of termites. The termite specificity of these
      lineages was underscored by the finding that the closest relatives of the
      bacterial clones obtained from R. santonensis were usually derived also from the
      most closely related termites. Overall, differences in diversity between the
      different gut habitats and the uneven distribution of individual phylotypes
      support conclusively that niche heterogeneity is a strong determinant of the
      structure and spatial organization of the microbial community in the termite gut.

PMID- 15946290
TI  - Design and validation of 16S rRNA probes to enumerate members of the Clostridium
      leptum subgroup in human faecal microbiota.
AB  - Among human faecal bacteria, many members of the Clostridium leptum subgroup are
      fibrolytic and butyrate producing microorganisms thereby contributing to
      processes important to colonic health. Yet this phylogenetic subgroup remains
      poorly described to date. To improve detection and description of members of the
      C. leptum subgroup, the Clep 866 group probe was developed. Its association with
      probes targeting the Clostridium viride cluster (Cvir 1414) and Eubacterium
      desmolans species (Edes 635) allowed for the first time the detection of all
      members found in this phylogenetic group in human faecal microbiota. A species
      specific probe was also designed to detect members of the Ruminococcus callidus
      species (Rcal 733). The design of signature regions was based on alignment of 16S
      rRNA sequences isolated from faeces of five healthy adults. Furthermore, an
      oligonucleotide competitor strategy was developed in order to improve the
      specificity of the probes formerly validated or designed in this study. The
      oligonucleotide probes were tested using a collection of target and non-target
      strains using FISH combined with flow cytometry. These new probes were added to a
      panel of 18 phylogenetic probes selected to describe faecal microbiota
      composition in 21 human faeces of healthy adults. Clostridium leptum subgroup
      represented 22% of the total faecal bacteria and codominated with members of
      Clostridium coccoides group. The cluster Faecalibacterium prausnitzii was the
      dominant component of the C. leptum subgroup and 20% of the latter subgroup
      remained unidentified at the species level.

PMID- 15946291
TI  - Investigation of the methanogen population structure and activity in a brackish
      lake sediment.
AB  - The methanogen community in sediment from the edge of a small brackish lake
      connected to the Beaulieu Estuary (Hampshire, UK) was investigated by analysis of
      16S rRNA gene diversity using new methanogen-specific primers plus Archaea
      specific primers. 16S rRNA gene primers previously used for polymerase chain
      reaction (PCR) detection of methanogenic Archaea from a variety of environments
      were evaluated by in silico testing. The primers displayed variable coverage of
      the four main orders of methanogens, highlighting the importance of this type of
      primer evaluation. Three PCR primer sets were designed using novel reverse
      primers to facilitate specific amplification of the orders
      Methanomicrobiales/Methanosarcinales, Methanobacteriales and Methanococcales.
      Diversity of the methanogen functional gene, methyl coenzyme M reductase (mcrA),
      was also studied. All gene libraries constructed from this sediment indicated
      that Methanomicrobiales and Methanosarcinales were the only methanogens detected.
      There was good agreement between the relative sequence abundances in the
      methanogen-specific 16S rRNA gene library and terminal restriction fragment
      length polymorphism (T-RFLP) profiling, suggesting that the population was
      dominated by putative H2 CO2 utilizing Methanomicrobiales, although acetate
      utilizing methanogens were also present. The methanogen population analyses were
      in agreement with methanogenic activity measurements, which indicated that
      bicarbonate methanogenesis was higher than acetate methanogenesis at all depths
      measured and overall there was a significant difference (P = 0.001) between the
      rates of the two pathways. This study demonstrates the utility of new 16S rRNA
      gene PCR primers targeting specific methanogenic orders, and the combined results
      suggest that the CO2 reduction pathway dominates methanogenesis in the brackish
      sediment investigated.

PMID- 15946292
TI  - An improved method for counting bacteria from sediments and turbid environments
      by epifluorescence microscopy.
AB  - We present a new procedure for effectively detaching particle-associated bacteria
      by 10% (v/v) methanol and sonication which is particularly suitable for samples
      with a high particle load and sediments. We also optimized the sample preparation
      by applying the highly dsDNA-specific fluorescent stain SybrGreen I together with
      an optically brilliant mounting medium (polyvinylalcohol 4-88, 'moviol') in one
      step. The new protocol allows a much faster, easy and less toxic handling of
      samples as compared to other methods. Cells are stained directly on a black
      Nuclepore filter and show an intensive fluorescence signal with low background.
      The detachment procedure was optimized with respect to the temperature of the 10%
      methanol solution (35 degrees C), ultrasonication and centrifugation. The
      application of the new method in comparison with detachment procedures with
      pyrophosphate and Tween-80 with various types of marine samples including
      sediments always yielded higher numbers and/or higher fractions of particle
      associated cells. Staining and mounting the samples with the moviol-SybrGreen I
      solution allowed an accurate and highly reproduceable enumeration of bacteria
      also in samples with high concentrations of SPM. Fixation of bacteria by
      glutardialdehyde resulted in a brighter fluorescence as compared to fixation by
      formalin. Because of the high specificity to dsDNA and bright fluorescence of
      SybrGreen I, the fast and easy handling and the possibility to store stained
      samples for at least several months at -20 degrees C without any loss in
      fluorescence intensity, the newly developed method is also an attractive
      alternative to DAPI staining of aquatic bacteria.

PMID- 15946293
TI  - Global Pseudomonas aeruginosa biodiversity as reflected in a Belgian river.
AB  - The biodiversity of the bacterium Pseudomonas aeruginosa in an aquatic
      environment (the Woluwe River, Brussels, Belgium) was analysed. Surface water was
      sampled bimonthly over a 1-year period (2000-2001) at seven sites evenly
      dispersed over the river. Total bacterial counts were performed and P. aeruginosa
      strains were isolated on a selective medium. A weighed out sample of 100 randomly
      chosen presumptive P. aeruginosa isolates was further analysed. A set of data
      consisting of the nucleotide sequence of the oprL gene, a DNA-based fingerprint
      (amplified fragment length polymorphism, AFLP), serotype, pyoverdine type and
      antibiogram (MICs of 21 clinically relevant antibiotics) was assembled. These
      data were integrated with those previously obtained for 73 P. aeruginosa clinical
      and environmental isolates collected across the world. The combined results were
      analysed and compared using biological data analysis software. Our findings
      indicate a positive relationship between the extent of pollution and the
      prevalence of P. aeruginosa. Surprisingly, the Woluwe River P. aeruginosa
      community was almost as diverse as the global P. aeruginosa population. Indeed,
      the Woluwe River harboured members of nearly all successful clonal complexes.
      With the exception of one multidrug-resistant (MDR) strain, belonging to a
      ubiquitous and clinically relevant serotype O11 clone, antibiotic resistance
      levels were relatively low. These findings illustrate the significance of river
      water as a reservoir and source of distribution of potentially pathogenic P.
      aeruginosa strains and could have repercussions on antinosocomial infection
      strategies.

PMID- 15946294
TI  - Persister cells, the biofilm matrix and tolerance to metal cations in biofilm and
      planktonic Pseudomonas aeruginosa.
AB  - In this study, we examined Pseudomonas aeruginosa ATCC 27853 biofilm and
      planktonic cell susceptibility to metal cations. The minimum inhibitory
      concentration (MIC), the minimum bactericidal concentration (MBC) required to
      eradicate 100% of the planktonic population (MBC 100), and the minimum biofilm
      eradication concentration (MBEC) were determined using the MBEC trade mark-high
      throughput assay. Six metals - Co(2+), Ni(2+), Cu(2+), Zn(2+), Al(3+) and Pb(2+)-
      were each tested at 2, 4, 6, 8, 10 and 27 h of exposure to biofilm and planktonic
      cultures grown in rich or minimal media. With 2 or 4 h of exposure, biofilms were
      approximately 2-25 times more tolerant to killing by metal cations than the
      corresponding planktonic cultures. However, by 27 h of exposure, biofilm and
      planktonic bacteria were eradicated at approximately the same concentration in
      every instance. Viable cell counts evaluated at 2 and 27 h of exposure revealed
      that at high concentrations, most of the metals assayed had killed greater than
      99.9% of biofilm and planktonic cell populations. The surviving cells were
      propogated in vitro and gave rise to biofilm and planktonic cultures with normal
      sensitivity to metals. Further, retention of copper by the biofilm matrix was
      investigated using the chelator sodium diethlydithiocarbamate. Formation of
      visible brown metal-chelates in biofilms treated with Cu(2+) suggests that the
      biofilm matrix may coordinate and sequester metal cations from the aqueous
      surroundings. Overall, our data suggest that both metal sequestration in the
      biofilm matrix and the presence of a small population of 'persister' cells may be
      contributing factors in the time-dependent tolerance of both planktonic cells and
      biofilms to high concentrations of metal cations.

PMID- 15946295
TI  - Study of the occurrence of Vibrio vulnificus in oysters in India by polymerase
      chain reaction (PCR) and heterogeneity among V. vulnificus by randomly amplified
      polymorphic DNA PCR and gyrB sequence analysis.
AB  - The pathogenic bacterium Vibrio vulnificus is widely distributed in estuarine
      waters throughout the world. In this study, the presence of V. vulnificus in
      oysters was studied both by conventional culture and DNA-based molecular
      technique. Following enrichment in alkaline peptone water (APW), the bacteria
      were lysed and a nested polymerase chain reaction (PCR) for vvhA gene was
      performed. The effect of duration of enrichment on the sensitivity of detection
      by PCR was evaluated. The organism was isolated from 43% of samples after 18 h
      enrichment in APW by conventional culture method. Nested PCR amplifying a
      fragment of vvhA gene detected the organism in 11%, 60% and 81% of samples
      following 0, 6 and 18 h of enrichment. All the biochemically identified V.
      vulnificus strains possessed vvhA gene and belonged to biotype 1. The genetic
      relatedness among the strains was studied by randomly amplified polymorphic DNA
      (RAPD) PCR and gyrB sequence analysis. The results suggest the presence of two
      distinct clonal groups of V. vulnificus in oysters in India. The study
      demonstrates, for the first time that gyrB sequence analysis could be used to
      study the genetic diversity of V. vulnificus.

PMID- 15946296
TI  - Intracellular survival and replication of Vibrio cholerae O139 in aquatic free
      living amoebae.
AB  - Vibrio cholerae is a highly infectious bacterium responsible for large outbreaks
      of cholera among humans at regular intervals. A seasonal distribution of
      epidemics is known but the role of naturally occurring habitats are virtually
      unknown. Plankton has been suggested to play a role, because bacteria can attach
      to such organisms forming a biofilm. Acanthamoebea castellanii is an
      environmental amoeba that has been shown to be able to ingest and promote growth
      of several bacteria of different origin. The aim of the present study was to
      determine whether or not an intra-amoebic behaviour of V. cholerae O139 exists.
      Interaction between these microorganisms in co-culture was studied by culturable
      counts, gentamicin assay, electron microscopy, and polymerase chain reaction. The
      interaction resulted in intra-amoebic growth and survival of V. cholerae in the
      cytoplasm of trophozoites as well as in the cysts of A. castellanii. These data
      show symbiosis between these microorganisms, a facultative intracellular
      behaviour of V. cholerae contradicting the generally held view, and a role of
      free-living amoebae as hosts for V. cholerae O139. Taken together, this opens new
      doors to study the ecology, immunity, epidemiology, and treatment of cholera.

PMID- 15946297
TI  - Biogeochemical processes in the saline meromictic Lake Kaiike, Japan:
      implications from molecular isotopic evidences of photosynthetic pigments.
AB  - Stable carbon and nitrogen isotopic compositions were determined for individual
      photosynthetic pigments isolated and purified from the saline meromictic Lake
      Kaiike, Japan, to investigate species-independent biogeochemical processes of
      photoautotrophs in the natural environment. In the anoxic monimolimnion and
      benthic microbial mats, the carbon isotopic compositions of BChls e and
      isorenieratene related to brown-coloured strains of green sulfur bacteria are
      substantially ( approximately 10 per thousand) depleted in (13)C relative to
      those found in the chemocline. In conjunction with 16S rDNA evidence reported
      previously, it strongly suggests that Pelodyctyon luteolum inhabited and
      photosynthesized in the anoxic monimolimnion and benthic microbial mats by using
      (13)C-depleted regenerated CO(2). By contrast, both Chl a and BChl a in the
      monimolimnion and microbial mats have similar isotopic compositions as they do in
      the chemocline, implying that the source organisms live only in the chemocline.
      In the chemocline, the nitrogen isotopic compositions of BChl e homologues ranges
      from -7.7 to-6.5 per thousand, whereas that of BChl a is -2.1 per thousand. These
      isotopic compositions suggest that green sulfur bacteria Chlorobium
      phaeovibrioides would conduct nitrogen fixation in the chemocline, whereas purple
      sulfur bacteria Halochromatium sp. and cyanobacteria Synechococcus sp. may
      assimilate nitrite.

PMID- 15946298
TI  - Gene sequence heterogeneity of Corallococcus coralloides strains isolated from
      geographically diverse locations.
AB  - Thirty-three strains classified as Corallococcus coralloides isolated from mostly
      soil samples in 14 countries of four continents, were subjected to phylogenetic
      analyses. Based on 16S rDNA analyses the strains form a highly related cluster,
      sharing above 98.7% sequence similarity. Four groups were recognized within this
      cluster, only one of which, containing two strains from St. Lucia, Lower
      Antilles, was exclusively defined by strains from the same sample. The other
      groups contained members from different countries, even continents. The largest
      group embraced the type strains of C. coralloides DSM 2259(T) and Corallococcus
      exiguus 14696(T) which were almost indistinguishable in their 16S rRNA gene
      sequence. Corallococcus macrosporus DSM 14697(T) grouped outside the C.
      coralloides cluster, showing a higher relationship to a member of Myxococcus. The
      topology of the tree generated on the basis of the partial gyrase B (gyrB) gene
      sequence supports the rRNA gene tree, though some differences in the order of
      branching were observed. As judged by the binary similarity values the higher
      resolution power of gyrB sequences was confirmed. From a taxonomic standpoint,
      the size of myxospores is not a valuable taxonomic criterion, as small- and
      medium-sized myxospores are members of the same group. If the species status of
      C. coralloides and C. exiguus is verified by other methods (e.g. DNA-DNA
      hybridisation, RiboTyping), the genus Corallococcus may embrace a broad range of
      yet-to-be described novel species. The presence of strains within the same sample
      displaying higher relatedness to strains from other locations points towards an
      intensive dispersal of myxospores across continents.

PMID- 15946299
TI  - Multiple displacement amplification as a pre-polymerase chain reaction (pre-PCR)
      to process difficult to amplify samples and low copy number sequences from
      natural environments.
AB  - Microbial assessment of natural biodiversity is usually achieved through
      polymerase chain reaction (PCR) amplification. Deoxyribonucleic acid (DNA)
      sequences from natural samples are often difficult to amplify because of the
      presence of PCR inhibitors or to the low number of copies of specific sequences.
      In this study, we propose a non-specific preamplification procedure to overcome
      the presence of inhibitors and to increase the number of copies prior to carrying
      out standard amplification by PCR. The pre-PCR step is carried out through a
      multiple displacement amplification (MDA) technique using random hexamers as
      priming oligonucleotides and phi 29 DNA polymerase in an isothermal, whole-genome
      amplification reaction. Polymerase chain reaction amplification using specific
      priming oligonucleotides allows the selection of the sequences of interest after
      a preamplification reaction from complex environmental samples. The procedure
      (MDA-PCR) has been tested on a natural microbial community from a hypogean
      environment and laboratory assemblages of known bacterial species, in both cases
      targeting the small subunit ribosomal RNA gene sequences. Results from the
      natural community showed successful amplifications using the two steps protocol
      proposed in this study while standard, direct PCR amplification resulted in no
      amplification product. Amplifications from a laboratory assemblage by the two
      step proposed protocol were successful at bacterial concentrations >or= 10-fold
      lower than standard PCR. Amplifications carried out in the presence of different
      concentrations of fulvic acids (a soil humic fraction) by the MDA-PCR protocol
      generated PCR products at concentrations of fulvic acids over 10-fold higher than
      standard PCR amplifications. The proposed procedure (MDA-PCR) opens the
      possibility of detecting sequences represented at very low copy numbers, to work
      with minute samples, as well as to reduce the negative effects on PCR
      amplifications of some inhibitory substances commonly found in environmental
      samples.

PMID- 15946300
TI  - Worldwide distribution of Pseudomonas aeruginosa clone C strains in the aquatic
      environment and cystic fibrosis patients.
AB  - Highly successful bacterial clones have the ability to effectively colonize
      environmental niches and patients. However, the factors which determine the
      complex interplay between the colonization of environmental niches and patients
      are mainly unknown. In this study we show that Pseudomonas aeruginosa clone C
      strains are distributed worldwide and highly prone to infect cystic fibrosis (CF)
      patients in Canada, England, France and Germany. In Hanover, Germany and
      Vancouver, Canada, clone C strains are highly prevalent in the CF patient
      community, although the mechanisms of acquisition may have been different. All
      clone C strains showed highly related macrorestriction fragment pattern of the
      whole genome as visualized by pulsed-field gel electrophoresis and harboured the
      102 kbp plasmid pKLC102. Comparison of three prevalent P. aeruginosa clones with
      different distribution between the environment and patients revealed that neither
      enhanced biofilm formation nor antibiotic resistance was responsible for the
      spread of clone C. Clone M, which was highly prevalent in the clinical
      environment such as sanitary facilities, lacked motility, which could explain its
      relatively low prevalence in CF patients. Elucidation of the mechanisms which
      lead to the prevalence of clone C strain in patients and the environment requires
      the investigation of additional phenotypes.

PMID- 15946301
TI  - Culturable marine actinomycete diversity from tropical Pacific Ocean sediments.
AB  - Actinomycetes were cultivated using a variety of media and selective isolation
      techniques from 275 marine samples collected around the island of Guam. In total,
      6425 actinomycete colonies were observed and 983 (15%) of these, representing the
      range of morphological diversity observed from each sample, were obtained in pure
      culture. The majority of the strains isolated (58%) required seawater for growth
      indicating a high degree of marine adaptation. The dominant actinomycete
      recovered (568 strains) belonged to the seawater-requiring marine taxon
      'Salinospora', a new genus within the family Micromonosporaceae. A formal
      description of this taxon has been accepted for publication (Maldonado et al.,
      2005) and includes a revision of the generic epithet to Salinispora gen. nov.
      Members of two major new clades related to Streptomyces spp., tentatively called
      MAR2 and MAR3, were cultivated and appear to represent new genera within the
      Streptomycetaceae. In total, five new marine phylotypes, including two within the
      Thermomonosporaceae that appear to represent new taxa, were obtained in culture.
      These results support the existence of taxonomically diverse populations of
      phylogenetically distinct actinomycetes residing in the marine environment. These
      bacteria can be readily cultured using low nutrient media and represent an
      unexplored resource for pharmaceutical drug discovery.

PMID- 15946302
TI  - Symbiotic and saprophytic survival of three unmarked Rhizobium leguminosarum
      biovar trifolii strains introduced into the field.
AB  - The symbiotic and saprophytic persistence of three unmarked Rhizobium
      leguminosarum biovar trifolii (Rlt) strains introduced into a field site in
      Iceland were followed. This site was free of clover cultivation and initially
      devoid of clover-nodulating rhizobia as tested by nodulation studies. Nodule
      occupancy by strains was identified based on their distinct ERIC-polymerase chain
      reaction (PCR) DNA fingerprint patterns. The survival and persistence of the
      individual strains in soil were monitored by the quantitative real-time PCR (qRT
      PCR) assay, targeting the host-specific nodE gene. The most dominant strain in
      the nodule population, Rlt 20-15, showed relatively less saprophytic survival
      ability and maintained high numbers only in the presence of the appropriate host
      plant. Conversely, the minor nodule occupant, Rlt 32-28, persisted in soil at a
      relatively higher abundance both in the presence of its host legumes and in the
      presence of a non-host grass. The qRT-PCR assay was successfully applied to
      quantify rhizobial strains directly in soil without culturing or nodulation.
      However, the assay demonstrated less sensitivity compared with the plant
      infection most-probable-number (MPN) method for estimating the population size of
      rhizobia in soil. The quantitative detection limit of our qRT-PCR assays was 1 x
      10(3) cells per gram of soil, as opposed to the MPN test which has a detection
      limit of 10 cells per gram of soil.

PMID- 15946304
TI  - Neutropenic enterocolitis in adults: systematic analysis of evidence quality.
AB  - OBJECTIVE: Neutropenic enterocolitis is a life-threatening complication occurring
      most frequently after intensive chemotherapy in acute leukaemias. The literature
      is heterogeneous and a systematic review is lacking. METHODS: Following a
      systematic search we categorised all relevant reports according to their quality
      and extracted evidence to answer the questions: Which diagnostic criteria are
      appropriate? What is the incidence of neutropenic enterocolitis? Are there good
      quality studies supporting specific interventions: Which empiric antimicrobial
      therapy is recommendable? Is neutropenic enterocolitis without surgical emergency
      complications an indication for bowel resection? RESULTS: We found and analysed
      145 articles of these reports: 64 were reports of single cases, 30 papers
      reported of two or three cases, 13 were narrative reviews, 34 were retrospective
      case series of more than three cases and four were prospective diagnostic
      studies. There were no prospective trials or case control studies on the therapy
      of neutropenic enterocolitis. There was no consensus on diagnostic criteria. We
      discuss the difficulty to define diagnostic criteria without having a disease
      definition. Histology is mostly not available in the living patients. We suggest
      applying a combination of clinical and radiological criteria: fever, abdominal
      pain and any bowel wall thickening >4 mm detected by ultrasonography (US) or
      computed tomography. We calculated a pooled incidence rate from 21 studies of
      5.3% (266/5058; 95% CI: 4.7%-5.9%) in patients hospitalised for haematological
      malignancies, for high-dose chemotherapy in solid tumours or for aplastic
      anaemia. CONCLUSIONS: This systematic review provides diagnostic criteria for
      neutropenic enterocolitis, presents a quantitative synthesis on its incidence and
      discusses its treatment recommendations. Prospective studies are clearly
      warranted.

PMID- 15946305
TI  - Preoperative transfusion in sickle cell disease: a survey of practice in England.
AB  - OBJECTIVES: To gather data on current preoperative transfusion practice and
      postoperative complications in sickle cell disease (SCD) as a prelude to a
      randomised trial. METHODS: A prospective one year survey of 114 SCD patients
      undergoing elective surgery in 31 English hospitals was undertaken. RESULTS: 43%,
      39% and 23% of patients respectively [corrected] received no transfusion, top-up
      and exchange transfusion preoperatively. Overall postoperative complication rates
      were 18%, 26% and 17%, with SCD related complications of 12%, 8% and 0%
      respectively. 85% of patients with [corrected]HbSC/HbSss(+)thalassaemia and 71%
      of obstetric and gynaecology patients were not transfused preoperatively, whereas
      59% patients undergoing ENT procedures and 83% of hip replacements had top-up and
      exchange transfusions respectively. Multivariable logistic regression analysis
      revealed that having moderate/high risk procedures was a predictor of
      postoperative complications (OR 4.9 (95% CL: 1.3 to 18), P = 0.017) [corrected]
      while preoperative transfusion was not (OR 1.7, (95% CL: [corrected] 0.5 to 6), P
      = 0.41). CONCLUSION: The lack of clear benefit of transfusion confirms the need
      for a randomised controlled trial of transfusion vs. no transfusion in patients
      with HbSS and HbSss(0)thalassaemia.

PMID- 15946306
TI  - Unrelated bone marrow transplantation for high-risk anaplastic large cell
      lymphoma in pediatric patients: a single center case series.
AB  - OBJECTIVES: The use of allogeneic stem cell transplantation in NHL patients is
      not yet clearly defined, especially in children and adolescents, but this option
      offers the advantages of a tumor-free graft and the possible induction of a graft
      vs.-tumor effect. PATIENTS AND METHODS: We report the results of four consecutive
      pediatric patients affected by anaplastic large cell lymphoma (ALCL) and treated
      with allogeneic stem cell transplantation from an unrelated donor. The
      conditioning regimen was based on total body irradiation given in association
      with etoposide in three patients, and with thiotepa and cyclophoshamide in one
      patient. Graft-vs.-host disease (GVHD) prophylaxis consisted of cyclosporin, a
      short course of methotrexate and rabbit antithymocyte globulin. RESULTS: All
      patients had rapid engraftment within 3-4 wk for neutrophils and platelets, and
      achieved a stable full donor chimerism that has been maintained to the last
      follow-up visit. One patient later developed a restrictive pneumonopathy. This
      patient had been heavily pretreated during the course of the disease having
      suffered four relapses and had received a cumulative dose of bleomycin of 160
      mg/m(2). After a follow-up of 11-42 months, all patients are alive in complete
      hematological and molecular remission; and three of them without any chronic
      GVHD. CONCLUSIONS: The increasing number of volunteer bone marrow donors and the
      reduced toxicity of unrelated stem cell transplantation, especially in children,
      make this therapeutic option worth more extensive investigation in the treatment
      of high-risk failure ALCL, although more data is needed to evaluate the long-term
      benefits. In this regard, the presence of factors predictive of worst outcome
      such as an early relapse (within 12 months from diagnosis), a refractory or
      relapsing ALCL and the persistent detection on blood or bone marrow of
      nucleophosmin-anaplastic lymphoma kinase protein (NPM-ALK) transcript may help
      select the patients eligible to allogeneic related or unrelated stem cell
      transplantation.

PMID- 15946307
TI  - Autologous stem cell transplantation in multiple myeloma: outcome in patients
      with renal failure.
AB  - The impact of renal failure on prognosis of multiple myeloma patients treated
      with high-dose chemotherapy and stem cell support is incompletely studied. A
      total of 137 patients received high-dose chemotherapy with autologous
      transplantation at our centre. The patient population was divided into three
      groups based on their estimated creatinine clearance (Ccr); renal failure defined
      as Ccr < 60 mL/min: Group A: normal renal function both at diagnosis and at
      transplant (n = 78), Group B: renal failure at diagnosis but normal renal
      function at transplant (n = 30), Group C: renal failure both at diagnosis and at
      transplant (n = 29). There were no differences in the number of stem cells
      harvested, time to engraftment or response to transplantation between the groups.
      Ten of the patients in Group C had a normalisation of renal function post
      transplant. Significantly longer hospitalisation, increased use of blood products
      and increased number of infections were seen in Group C compared to Groups A and
      B. The transplant-related mortality was 17% in Group C compared to 0% and 1% in
      Groups B and A respectively. Eight patients were on dialysis during transplant
      and four of these died within the first 100 d post-transplant. Disease response
      was similar in the three groups. Overall survival was significantly longer in
      Group A than in Groups B and C. High-dose chemotherapy with autologous
      transplantation is feasible in MM with renal failure. Whereas patients with
      moderate renal insufficiency seem to benefit from this treatment, patients in
      need for dialysis at the time of transplant must be carefully evaluated before
      proceeding to high-dose chemotherapy.

PMID- 15946308
TI  - Mitogen induced activation, proliferation and surface antigen expression patterns
      in unmutated and hypermutated chronic lymphocytic leukemia cells.
AB  - OBJECTIVES: To determine whether the immunoglobulin V(H) gene mutational status
      has an effect on the activation, proliferation and surface antigen expression of
      chronic lymphocytic leukemia (CLL) cells when stimulated in vitro. METHODS: The
      proliferation and activation responses of CLL cells were studied in 22
      immunoglobulin gene V(H) unmutated (UM-CLL) and 12 hypermutated (M-CLL) CLL cases
      in 4-day cultures. As the mitogen responses have been previously shown to be
      diverse in CLL, a case-specific strategy based on optimized mitogen combinations
      (OMCs) of interleukin-2 (IL-2), 12-O-tetradecanoylphorbol 13-acetate (TPA),
      Staphylococcus aureus Cowan 1 (SAC), and human recombinant tumor necrosis factor
      alpha (TNF) was applied in cell stimulation. The expression of 23 surface
      membrane antigens (CD5, CD11c, CD19, CD20, CD21, CD22, CD23, CD25, CD27, CD38,
      CD40, CD45, CD45RA, CD45RO, CD79b, CD80, CD95, CD124, CD126, CD130, FMC7, IgD,
      and IgM) was studied by flow cytometry at days 0 and 4. RESULTS: The
      proliferation and activation responses were similar in UM-CLL and M-CLL when OMCs
      contained IL-2, TPA or TNF. SAC induced faster proliferation in UM-CLL than in M
      CLL. OMC stimulation induced preferential down-regulation of growth- promoting
      cell surface receptors CD5, CD21, and CD124 and preferential up-regulation of
      growth-inhibiting antigen CD80 in M-CLL. CONCLUSIONS: Difference in
      immunophenotypic evolution of UM-CLL and M-CLL can be demonstrated if appropriate
      matrix signals are provided. The pathways for CD5, CD21, CD124 (IL4R), and CD80
      (B7-1) regulation should be further explored in relation with somatic
      hypermutation and outcome of CLL.

PMID- 15946309
TI  - Anti-angiogenic effects and regression of localized murine AML produced by anti
      VEGF and anti-Flk-1 antibodies.
AB  - Reducing the blood supply of tumors is one modality to combat cancer. The
      objective of this study was to evaluate such an approach in the treatment of
      localized murine AML (acute myelogenous leukemia). For this purpose we designed
      an experimental model in which leukemic cells were embedded in 1% agar discs
      before subcutaneous implantation in C57Bl female mice. The C-1498 AML cell line
      (Frederick Inst., NCI, MD, USA) was used. Thirty experimental mice received on
      alternate days injections of 5 x 2.5 microg anti-VEGF (vascular endothelial
      growth factor) and 5 x 2.5 microg anti-Flk-1 (VEGFR2) antibodies to the site of
      cell implantation over a period of 10 d. Fifteen control mice received daily PBS
      injections. All mice were sacrificed 16 d after AML implantation. Of the 30
      experimental animals, macroscopic examination showed in 21 animals (70%) small
      sized, pale tumors (0.5 g); in six mice (20%) the tumors were replaced completely
      by necrotic tissue, while in three mice (10%), there were large (2.5 g), highly
      vascularized tumors. In all 15 control mice large highly vascularized tumors were
      seen. A separate group of mice was studied for total survival following AML
      implantation. While 12 mice in the control group not treated with antibodies
      survived for 16 d post-implantation, survival was prolonged in 15 antibody
      treated mice by approximate 30 d to a total survival time of 48 d. Tumor
      specimens were processed for histology, immunohistochemistry (IHC) for CD31
      endothelial cell antigen, and tube-like formation assay. The small, pale tumors
      of antibody treated animals consisted of degenerate hyaline material with remnant
      nests of leukemic cells, whereas large tumors showed sheets of leukemic cells and
      numerous blood vessels. Specimens processed for CD31 antigen showed scarce or
      absence of blood vessels in the small, pale tumors in contrast to intensive
      staining from a rich network of blood vessels in the large, highly vascularized
      tumors. Tube-like formation assays disclosed rudimentary Grade 1 endothelial cell
      tubes in the small, pale tumors as opposed to polygonal Grade 4 tube formation in
      control animals. In conclusion, this murine model of localized AML allows
      assessment of anti-angiogenic tumor regression. Anti-angiogenic antibodies
      against VEGF and Flk-1 have therapeutic effects in murine AML.

PMID- 15946310
TI  - Two beta-globin cluster-linked polymorphic loci in thalassemia patients of
      variable levels of fetal hemoglobin.
AB  - OBJECTIVE: To correlate different polymorphisms of the beta-globin cluster with
      fetal hemoglobin (HbF) level in beta-thalassemia and E-beta thalassemia patients.
      METHODS: Fifteen thalassemia patients, seven with high HbF and not requiring
      transfusion, eight with lower HbF and requiring transfusion were studied for beta
      globin mutation, concurrent inheritance of alpha-thalassemia, RFLP haplotype, a C
      ->T polymorphism at -158 of Ggamma and configuration of an (AT)(x)T(y) motif at 
      540 of beta-globin gene. RESULTS: Senegal 5'beta-haplotype and the polymorphism
      at -158 of G(gamma) was (P = 0.063) was linked to the high-HbF phenotype but the
      (AT)(9)T(5) configuration of the (AT)(x)T(y) motif was not (P = 0.6). Study of 30
      chromosomes revealed 7 different configurations of the (AT)(x)T(y) motif.
      Association of these motifs with specific beta-globin mutations of this region
      has also been determined. CONCLUSION: The senegal haplotype and the polymorphism
      at -158 of G(gamma) was linked to the high-HbF phenotype.

PMID- 15946311
TI  - Recurrent V75M mutation within the Wiskott-Aldrich syndrome protein: description
      of a homozygous female patient.
AB  - The Wiskott-Aldrich syndrome is a rare genetic disorder due to mutations in the
      WAS gene situated on chromosome X. It is comprised of microthrombocytopenia,
      eczema and immunodeficiency. However, the phenotypical presentation may vary as
      to the number and intensity of its manifestations. A milder form of Wiskott
      Aldrich syndrome is known as the X-linked thrombocytopenia. We independently
      found eight individual or familial cases with the V75M substitution (9.76%). This
      high incidence was partly accounted for by the fact that three cases turned out
      to be related. The V75M mutation is recurrent, however, due to a CpG island. A
      genuine homozygous female patient was found. She showed microthrombocytopenia and
      infections to the same degree as her hemizygous father and brother. The WAS
      protein was decreased in a comparable fashion in the hemizygotes and the
      homozygote as well. Its amount was about 10% and 15% of normal in platelets and
      mononucleated white cells, respectively. In all patients was the picture
      consistent with XLT.

PMID- 15946312
TI  - Efficacy of mycophenolate mofetil in adult refractory auto-immune cytopenias: a
      single center preliminary study.
AB  - Treatment of auto-immune cytopenia refractory to front line therapy with
      intravenous immunoglobulins and steroids is a matter of concern. We assessed the
      efficacy and safety of mycophenolate mofetil in a prospective open preliminary
      study. STUDY DESIGN: Adult patients with steroid refractory auto-immune
      cytopenias were included. Mycophenolate mofetil (MMF) was added to treatment
      given at the time of inclusion, and efficacy was evaluated in term of improvement
      of platelet/haemoglobin levels and in term of reduction of previously given
      drugs, if any. All auto-immune thrombocytopenic purpura (AITP) patients had
      serologic assessment for associated auto-antibodies at the time of inclusion.
      Cytopenias associated with other auto-immune diseases, lymphoproliferative
      diseases or HIV infection were excluded. RESULTS: From November 1999 through
      November 2003, 13 patients were included (nine AITP, three auto-immune haemolytic
      anaemia (AIHA), one Evans' syndrome; four males, nine females; age: 35-72 yr).
      For AITP patients, an overall response of 78% was observed. Retrospective
      analysis showed no significant difference between patients having a short disease
      duration (<1 yr) and longer disease duration; between patients who previously
      received more or less than three treatments; and between patients for whom MMF
      was started as monotherapy or in association with prednisone, However, all AITP
      patients presenting associated auto-antibodies responded to MMF, while only 50%
      of patients without associated antibodies were responders. All patients
      presenting AIHA and Evans' syndrome were responders. The drug was well tolerated,
      with no significant side effects reported. The cumulative data suggest a
      potential place for MMF in the treatment arsenal of refractory cytopenias.

PMID- 15946313
TI  - Pericardial graft vs. host disease in a patient with myelodysplastic syndrome
      following peripheral blood stem cell transplantation.
AB  - A patient with myelodysplastic syndrome developed pericardial effusion 20 month
      after allogenic peripheral blood stem cell transplantation. Sclerotic and
      erythematous skin lesions were observed over the face and extremities, and a
      diagnosis of chronic graft vs. host disease (GVHD) was made based on skin biopsy
      findings. Pericardial fluid contained numerous CD8+/HLA-DR+ lymphocytes, but no
      leukaemic cells. Tumour necrosis factor alpha (TNFalpha) and soluble Fas (sFas)
      levels were highly elevated in both the effusion and serum. The patient was
      treated with methylprednisolone and tacrolimus. Skin GVHD improved rapidly
      associated with resolution of pericardial effusion and reductions in cytokine
      levels. We concluded that pericardial effusion was due to pericarditis and was a
      manifestation of chronic GVHD in this patient, and that cytotoxic lymphocytes and
      specific cytokines played significant roles.

PMID- 15946314
TI  - Inflammatory pseudotumor of the lung following invasive aspergillosis in a
      patient with chronic graft-vs.-host disease.
AB  - Inflammatory myofibroblastic tumor (IMT) is an uncommon cause of solitary or
      multifocal lung nodules and can also be rarely found in various other
      extrapulmonary sites. Although this pseudotumor is benign, it can be locally very
      aggressive. The pathogenesis of IMT remains unclear; autoimmune or infectious
      origins have been hypothesized, so far. Here, we report a case of inflammatory
      pseudotumor of the lung secondary to invasive pulmonary aspergillosis in a
      patient with chronic graft-vs.-host disease. The 42-year-old patient presented
      with coughing and hemoptysis as major clinical signs 1 yr after successful HLA
      identical stem cell transplantation. Aspergillus fumigatus was cultured from the
      bronchoscopic lavage, but intensive antifungal treatment could only initially
      improve the clinical situation. Diagnostic re-evaluation by open-chest biopsy
      surprisingly revealed an inflammatory pseudotumor responsible for clinical and
      radiographical deterioration. Both clinical and radiographical signs resolved
      under long-term steroids and secondary antifungal prophylaxis.

PMID- 15946315
TI  - An unusual case of myelodysplastic syndrome with prolonged clonal stability,
      indolent clinical course over a decade, and spontaneous regression of AML in the
      terminal phase.
AB  - An unusual case of secondary acute myeloid leukemia (AML) with indolent clinical
      course is described. The patient, a 67-yr-old female, had first been diagnosed to
      suffer from low-risk myelodysplastic syndrome, subtype refractory anemia with
      ringed sideroblasts, in 1992. In 2001, transformation to secondary AML with an
      increase in bone marrow blasts (>20%) and thrombocytopenia, was found. The
      patient did not require cytoreductive drugs. Rather, during the following months,
      spontaneous improvement of peripheral blood cells with normalization of platelets
      and decrease in the red cell transfusion frequency, were noted. In October 2002,
      she even became transfusion independent. However, the bone marrow still showed
      AML with >20% blasts. These blast cells exhibited a monoclonal pattern in the
      human androgen receptor (HUMARA) assay. However, no chromosomal defects occurred
      during a total observation period of 14 yr. We hypothesize that clonal stability
      may have contributed to the indolent course of the disease in this patient. The
      exact mechanisms underlying clinical and genetic stability remain unknown,
      however.

PMID- 15946316
TI  - Immunophenotypic and genetic characterization of a CD8 positive mantle cell
      lymphoma in a patient with concomitant Mycosis fungoides.
AB  - Mantle cell lymphoma (MCL) is immunophenotypically characterized by cell surface
      co-expression of CD19, CD20, CD5, IgM and FMC7. However, the concomitant presence
      of other antigens distinctive of a particular leukocyte subset, e.g. T
      lymphocytes, is an exceptional finding in MCL. Here, the first case of a blastic
      MCL in leukaemic phase with aberrant expression of the T-cell associated antigen
      CD8 occurring in a patient with concomitant Mycosis fungoides is described.
      Comprehensive immunophenotypic analysis showed that the MCL cells expressed the
      typical B-lymphocytic markers, were CD5 and CD8 positive, but did not express
      other T-cell proteins, such as CD2, CD3, CD4, CD7, TCRalphabeta and
      TCRgammadelta. The MCL cells expressed both CD8alpha and CD8beta chains
      indicating cell surface presence of CD8alphabeta heterodimers. Intriguingly,
      expression of the cytotoxic enzymes perforin and granzyme A was detected by RT
      PCR. Cytogenetic and molecular genetic analysis of the lymphoma cells confirmed
      cyclin D1 overexpression secondary to the t(11;14)(q13;32) chromosomal
      translocation. Furthermore, trisomy 11, trisomy 14 and extra copies of t(11;14)
      translocated chromosomes were detected in sub clones of the analyzed MCL cells.
      Clinically, an aggressive course of disease including cerebral lymphoma
      involvement was noted in the reported patient. Hence, systematic studies
      addressing the incidence, biology and clinical behavior of this form of MCL seem
      to be justified in future.

PMID- 15946317
TI  - Macrophage Inflammatory Protein-1 alpha (MIP-1alpha) is over-expressed in a
      cohort of patients with myelodysplastic syndromes.

PMID- 15946318
TI  - Improved cardiac function in a patient with hypereosinophilic syndrome treated
      with imatinib.

PMID- 15946319
TI  - Can nifedipine and estrogen interaction with imatinib be responsible for
      gallbladder stone development?

PMID- 15946321
TI  - Vigabatrin in low doses selectively suppresses the clonic component of
      audiogenically kindled seizures in rats.
AB  - PURPOSE: The effect of systemic administration of the gamma-aminobutyric acid
      (GABA)-transaminase inhibitor vigabatrin (VGB) on different components of
      convulsions was tested in the model of audiogenically kindled seizures, which
      consist of brainstem (running, tonus) and forebrain (clonus) elements. METHODS:
      Audiogenically susceptible rats of Krushinsky-Molodkina (KM), Wistar, and WAG/Rij
      strains received repeated sound stimulation (60 dB, 10-80 kHz) until kindled
      audiogenic seizures were reliably elicited. Kindled audiogenic seizures consisted
      of running, tonic, and generalized clonic phases in KM rats (severe audiogenic
      seizures) and of running and Racine stage 5 facial/forelimb clonus in Wistar and
      WAG/Rij rats (moderate seizures). Vehicle, 100, or 200 mg/kg of VGB was
      intraperitoneally injected 2, 4 and 24 h before the induction of kindled
      audiogenic seizures. RESULTS: At both doses, VGB did not change the seizure
      latency and the duration of running and tonic convulsions, but suppressed clonic
      ones in all rat strains. In KM rats, the mean duration of posttonic clonus was
      significantly reduced at 24 h after 100 mg/kg and from 4 h after 200 mg/kg. In
      Wistar and WAG/Rij rats, the mean duration of facial/forelimb clonus was reduced
      from 4 and 2 h after 100- and 200-mg/kg administration, respectively; 24 h after
      the high-dose injection, clonus was completely blocked in all rats of both
      strains. No difference in efficacy of VGB between Wistar and WAG/Rij rats was
      observed. CONCLUSIONS: VGB more effectively suppresses clonic convulsions than
      running and tonic ones in audiogenically kindled rats. It is supposed that this
      selective anticonvulsive effect of VGB results from different sensitivities of
      forebrain and brainstem epileptic networks to the presumed GABA enhancement.

PMID- 15946322
TI  - Anticonvulsant properties of the novel nootropic agent nefiracetam in seizure
      models of mice and rats.
AB  - PURPOSE: Nefiracetam (NEF) is a novel pyrrolidone-type nootropic agent, and it
      has been reported to possess various pharmacologic effects as well as cognition
      enhancing effects. The present study focused on the anticonvulsant effect of NEF
      and its potential for antiepileptic therapy. METHODS: The anticonvulsant
      properties of NEF were investigated in experimental seizure models of mice and
      rats, compared with levetiracetam (LEV) and other standard antiepileptic drugs
      [AEDs; zonisamide (ZNS), phenytoin (PHT), carbamazepine (CBZ), valproic acid
      (VPA), diazepam (DZP), and ethosuximide (ESM)]. With reference to standard
      programs for evaluating potential AEDs, the study included the traditional
      maximal electroshock seizure and subcutaneous chemoconvulsant
      (pentylenetetrazole, bicuculline, picrotoxin, strychnine, or N-methyl-D
      aspartate) seizure tests and two threshold models (the increasing-current
      electroshock seizure test and intravenous pentylenetetrazole seizure threshold
      test). Neurotoxic activities were examined with the rotarod test and traction
      test. RESULTS: NEF inhibited electroshock-induced seizures at nontoxic doses,
      whereas it had no effect on seizures chemically induced by pentylenetetrazole,
      bicuculline, picrotoxin, strychnine, or N-methyl-D-aspartate. The anticonvulsant
      spectrum of NEF paralleled that of ZNS, PHT, and CBZ. The anticonvulsant efficacy
      of NEF was comparable with that of ZNS and less potent than that of PHT, CBZ, and
      DZP. However, the safety margin of NEF was superior to that of ZNS, CBZ, VPA, and
      DZP. LEV showed only slight anticonvulsant effects in threshold models, and it
      was not effective in conventional screening models. CONCLUSIONS: These results
      suggest that NEF has distinct anticonvulsant spectrum and mechanisms from those
      of LEV. NEF is an orally active and safe AED, and it possesses a potential for
      antiepileptic therapy.

PMID- 15946323
TI  - Anticonvulsant activity of androsterone and etiocholanolone.
AB  - PURPOSE: Men with epilepsy often have sexual or reproductive abnormalities that
      are attributed to alterations in androgen levels, including subnormal free
      testosterone. Levels of the major metabolites of testosterone-androsterone
      (5alpha-androstan-3alpha-ol-17-one; 5alpha,3alpha-A), a neurosteroid that acts as
      a positive allosteric modulator of GABA(A) receptors, and its 5beta-epimer
      etiocholanolone (5beta-androstan-3alpha-ol-17-one; 5beta,3alpha-A)-also may be
      reduced in epilepsy. 5alpha,3alpha-A has been found in adult brain, and both
      metabolites, which also can be derived from androstenedione, are present in
      substantial quantities in serum along with their glucuronide and sulfate
      conjugates. This study sought to determine whether these endogenous steroid
      metabolites can protect against seizures. METHODS: The anticonvulsant activity of
      5alpha,3alpha-A and 5beta,3alpha-A was investigated in electrical and
      chemoconvulsant seizure models in mice. The steroids also were examined for
      activity against extracellularly recorded epileptiform discharges in the CA3
      region of the rat hippocampal slice induced by perfusion with 55 microM 4
      aminopyridine (4-AP). RESULTS: Intraperitoneal injection of 5alpha,3alpha-A
      protected mice in a dose-dependent fashion from seizures in the following models
      (ED50, dose in mg/kg protecting 50% of animals): 6-Hz electrical stimulation
      (29.1), pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and maximal
      electroshock (224). 5beta,3alpha-A also was active in the 6-Hz and
      pentylenetetrazol models, but was less potent (ED50 values, 76.9 and 139 mg/kg,
      respectively), whereas epiandrosterone (5alpha,3beta-A) was inactive (ED50,
      <or=300 mg/kg). 5alpha,3alpha-A (10-100 microM) also inhibited epileptiform
      discharges in a concentration-dependent fashion in the in vitro slice model,
      whereas 5beta,3alpha-A was active but of lower potency, and 5alpha,3beta-A was
      inactive. CONCLUSIONS: 5alpha,3alpha-A and 5beta,3alpha-A have anticonvulsant
      properties. Although of low potency, the steroids are present in high abundance
      and could represent endogenous modulators of seizure susceptibility.

PMID- 15946324
TI  - In vivo modulatory action of extracellular glutamate on the anticonvulsant
      effects of hippocampal dopamine and serotonin.
AB  - PURPOSE: Our recent work (Clinckers et al., J Neurochem 2004;89:834-43)
      demonstrated that intrahippocampal perfusion of 2 nM dopamine or serotonin via a
      microdialysis probe offered complete protection against focal pilocarpine-induced
      limbic seizures and did not influence basal extracellular hippocampal glutamate
      levels. Ten nanomolar dopamine or serotonin perfusion, however, worsened seizures
      and was accompanied by significant extracellular glutamate increases to
      approximately 200%. The significance of these glutamate elevations in seizure
      generation remains unclear. The present microdialysis study investigated the
      modulatory role of extracellular hippocampal glutamate levels in these
      monoaminergic protective and proconvulsant effects. METHODS: A first group of
      male Wistar albino rats was perfused intrahippocampally for 240 min with 6.25
      microM glutamate alone to increase extracellular levels by 200%. Other animals
      were perfused with anticonvulsant concentrations of monoamines throughout the
      experiments while receiving continuous coperfusions of 6.25 microM glutamate
      either before, during, and after (240 min) or only after (100 min) pilocarpine
      perfusion (40 min). Rats were scored for epileptic behavior, and the mean scores
      were compared with those of the control group. Microdialysates were analyzed for
      monoamine and glutamate content with microbore liquid chromatography. RESULTS: No
      convulsions occurred during glutamate perfusion alone. When monoamines and
      glutamate were coperfused before pilocarpine administration, the anticonvulsant
      effect of the monoamines was lost. Glutamate addition after pilocarpine
      administration did not affect monoaminergic seizure protection. CONCLUSIONS:
      These results indicate that extracellular glutamate increases per se do not
      necessarily induce seizures but that they can modulate the anticonvulsant effects
      exerted by hippocampal monoamines.

PMID- 15946325
TI  - Short-term effects of kainic acid on CA1 hippocampal interneurons differentially
      vulnerable to excitotoxicity.
AB  - PURPOSE: We sought to identify the inhibitory interneurons of the rat hippocampal
      CA1 region selectively vulnerable in the kainic acid (KA) model of temporal lobe
      epilepsy and to determine whether their selective vulnerability could be due to
      differential short-term KA effects. METHODS: We quantified vulnerable
      interneurons in stratum oriens-alveus (O/A) by using immunohistochemistry for
      glutamic acid decarboxylase (GAD), parvalbumin (PV), and somatostatin (SS) after
      KA injections in rats, and then compared in normal slices the effects of KA on
      interneurons either in O/A (vulnerable to KA) or in strata radiatum and lacunosum
      moleculare (R/LM) (resistant to KA) by using whole-cell recording and calcium
      imaging. RESULTS: GAD-, PV- and SS-positive cells in O/A were decreased after KA
      treatment in P20 and P30 rats. Both short (1-min) and long (10-min) applications
      of KA produced similar tetrodotoxin (TTX)-insensitive membrane depolarization and
      decrease in input resistance in O/A and R/LM interneurons. KA responses were
      antagonized by CNQX and GYKI52466, suggesting AMPA receptor activation. KA also
      generated a similar increase in intracellular Ca2+ in O/A and R/LM interneurons,
      which was antagonized by CNQX and GYKI52466. CONCLUSIONS: The selective
      vulnerability of GAD-, PV-, and SS-immunopositive O/A interneurons in the KA
      model may not arise from cell-specific short-term membrane effects or calcium
      responses induced by KA, but from other glutamate receptor-mediated excitotoxic
      processes.

PMID- 15946326
TI  - Localization of breast cancer resistance protein (BCRP) in microvessel
      endothelium of human control and epileptic brain.
AB  - PURPOSE: Breast cancer resistance protein (BCRP) is a half adenosine triphosphate
      (ATP)-binding cassette (ABC) transporter expressed on cellular membranes and
      included in the group of multidrug resistant (MDR)-related proteins. Recently,
      upregulation of different MDR proteins has been shown in human epilepsy
      associated conditions. This study investigated the expression and cellular
      distribution of BCRP in human control and epileptic brain, including a large
      number of both neoplastic and nonneoplastic specimens from patients with chronic
      pharmacoresistant epilepsy. METHODS: Several epileptogenic pathologies, such as
      hippocampal sclerosis (HS), focal cortical dysplasia (FCD), dysembryoplastic
      neuroepithelial tumor, oligodendroglioma astrocytoma, and glioblastoma multiforme
      were studied by using Western blot and immunocytochemistry. RESULTS: With Western
      blot, we could demonstrate the presence of BCRP in both normal and epileptic
      human brain tissue. In contrast to P-glycoprotein (P-gp) and multidrug resistance
      associated protein (MRP) 2, BCRP expression levels did not change in tissue from
      patients with HS, compared with control hippocampus. No BCRP immunoreactivity was
      observed in glial or neuronal cells, including reactive astrocytes and dysplastic
      neurons in FCD. BCRP expression was, however, increased in tumor brain tissue.
      Immunocytochemistry demonstrated that BCRP was exclusively located in blood
      vessels and was highly expressed at the luminal cell surface and in newly formed
      tumor capillaries. This localization closely resembles that of P-gp. The higher
      expression observed in astrocytomas by Western blot analysis was related to the
      higher vascular density within the tumor tissue. CONCLUSIONS: These results
      indicate a constitutive expression of BCRP in human endothelial cells,
      representing an important barrier against drug access to the brain. In
      particular, the strong BCRP expression in the microvasculature of epileptogenic
      brain tumors could critically influence the bioavailability of drugs within the
      tumor and contribute to pharmacoresistance.

PMID- 15946327
TI  - Drug resistance in epilepsy: putative neurobiologic and clinical mechanisms.
AB  - Drug-resistant epilepsy with uncontrolled severe seizures despite state-of-the
      art medical treatment continues to be a major clinical problem for up to one in
      three patients with epilepsy. Although drug resistance may emerge or remit in the
      course of epilepsy or its treatment, in most patients, drug resistance seems to
      be continuous and to occur de novo. Unfortunately, current antiepileptic drugs
      (AEDs) do not seem to prevent or to reverse drug resistance in most patients, but
      add-on therapy with novel AEDs is able to exert a modest seizure reduction in as
      many as 50% of patients in short-term clinical trials, and a few become seizure
      free during the trial. It is not known why and how epilepsy becomes drug
      resistant, while other patients with seemingly identical seizure types can
      achieve seizure control with medication. Several putative mechanisms underlying
      drug resistance in epilepsy have been identified in recent years. Based on
      experimental and clinical studies, two major neurobiologic theories have been put
      forward: (a) removal of AEDs from the epileptogenic tissue through excessive
      expression of multidrug transporters, and (b) reduced drug-target sensitivity in
      epileptogenic brain tissue. On the clinical side, genetic and clinical features
      and structural brain lesions have been associated with drug resistance in
      epilepsy. In this article, we review the laboratory and clinical evidence to date
      supporting the drug-transport and the drug-target hypotheses and provide
      directions for future research, to define more clearly the role of these
      hypotheses in the clinical spectrum of drug-resistant epilepsy.

PMID- 15946328
TI  - Target-specific catecholamine elevation induced by anticonvulsant thalamic deep
      brain stimulation.
AB  - PURPOSE: Anterior thalamic nucleus (AN) deep brain stimulation (DBS) is effective
      in raising EEG and clonic seizure threshold in experimental models. Little is
      known about the specific properties of DBS that afford its anticonvulsant effect.
      We sought to test the hypothesis that experimental seizures and the
      anticonvulsant action of AN DBS alter the underlying regional neurochemistry of
      AN, specifically with facilitation of the serotonergic system to local electrical
      stimulation. METHODS: Halothane-anesthetized adult Sprague-Dawley male rats
      underwent stereotactically guided bilateral placement of bipolar stimulating
      steel electrodes and dialysis probes-guide cannulae in AN and posterior thalamus
      (PT), and placement of four epidural EEG screw electrodes 48 h before
      experiments. Both stimulated (AN DBS) and nonstimulated (NO DBS) animals (n=7 per
      group) were infused with i.v. pentylenetetrazol (PTZ, 5.5 mg/kg/min).
      Simultaneous thalamic and cortical EEG were recorded, and microdialysis samples
      were collected from AN and PT in 20-min epochs. AN stimulation was delivered (150
      microA; 0.1-ms pulse duration) 40 min before and continued during PTZ infusion.
      RESULTS: Bilateral AN stimulation delayed the onset of EEG seizures compared with
      controls: 82+/-8 vs. 58+/-5 min (p=0.02). PTZ infusion alone, or together with
      stimulation, resulted in a steady increase in norepinephrine (NE), but not
      dopamine, at AN and PT sites (p<0.001). Although extracellular serotonin was
      measured at very low levels, the metabolite, 5-hydroxyindoleacetic acid (5-HIAA)
      increased selectively in AN after stimulation and during preconvulsant infusion
      of PTZ (p<0.001), returning to baseline after the first generalized seizure.
      CONCLUSIONS: These data suggest that PTZ and DBS together enhance the
      nonselective release of NE in thalamic nuclei while specifically stimulating AN
      localized serotonin. Low serotonin levels at baseline and during STIM alone or
      PTZ infusion may indicate efficient reuptake systems for serotonin, with 5-HIAA
      serving as a surrogate marker for serotonergic activity. Modulation of the AN
      specific serotonergic activity may be critical in altering PTZ seizure threshold
      and be an important neurotransmitter system underlying the efficacy of AN DBS.

PMID- 15946329
TI  - Early thalamic injury associated with epilepsy and continuous spike-wave during
      slow sleep.
AB  - PURPOSE: Mechanisms inducing continuous spike-wave during slow sleep (CSWS) in
      encephalopathy with electrical status epilepticus during sleep are still unclear.
      Recently, some sporadic cases with early thalamic injury associated with CSWS
      have been reported. The aim of the study was to investigate in a population of
      patients with an early thalamic injury the presence of an activation of
      paroxysmal activities during sleep, their characteristics, and possible relations
      to neuroimaging and neuropsychological features. METHODS: Thirty-two patients
      with prenatal or perinatal thalamic injuries, mostly due to a vascular
      mechanisms, were fully examined, including neuroimaging, EEG monitoring, and
      cognitive follow-up. RESULTS AND CONCLUSIONS: Twenty-nine of 32 patients showed
      major sleep EEG activation. Among these 29 patients, two different groups were
      distinguished: the first included the more or less typical CSWS (12 cases),
      generally with symmetry of spike and waves (SWs) and often with no spindle at
      all. The other cases had an usual asymmetry of SWs and presence or reduction of
      spindles, plus other atypical features concerning synchronism and morphology of
      SWs. Behavioral disorders were significantly more present in patients with a true
      CSWS; their improvement (and in one case of the three thoroughly followed the
      improvement of cognitive competence) paralleled the disappearance of CSWS. The
      generally predominant injury of the lateral aspect of the thalamus included
      reticular nucleus and ventral nuclei. An imbalance of gamma-aminobutyric acid
      (GABA)(B)--versus GABA(A)--mediated receptors may be evoked as a cofactor
      predisposing to CSWS.

PMID- 15946330
TI  - Computerized motion analysis of videotaped neonatal seizures of epileptic origin.
AB  - PURPOSE: The main objective of this research is the development of automated
      video processing and analysis procedures aimed at the recognition and
      characterization of the types of neonatal seizures. The long-term goal of this
      research is the integration of these computational procedures into the
      development of a stand-alone automated system that could be used as a supplement
      in the neonatal intensive care unit (NICU) to provide 24-h per day noninvasive
      monitoring of infants at risk for seizures. METHODS: We developed and evaluated a
      variety of computational tools and procedures that may be used to carry out the
      three essential tasks involved in the development of a seizure recognition and
      characterization system: the extraction of quantitative motion information from
      video recordings of neonatal seizures in the form of motion-strength and motor
      activity signals, the selection of quantitative features that convey some unique
      behavioral characteristics of neonatal seizures, and the training of artificial
      neural networks to distinguish neonatal seizures from random infant behaviors and
      to differentiate between myoclonic and focal clonic seizures. RESULTS: The
      methods were tested on a set of 240 video recordings of 43 patients exhibiting
      myoclonic seizures (80 cases), focal clonic seizures (80 cases), and random
      infant movements (80 cases). The outcome of the experiments verified that optical
      flow methods are promising computational tools for quantifying neonatal seizures
      from video recordings in the form of motion-strength signals. The experimental
      results also verified that the robust motion trackers developed in this study
      outperformed considerably the motion trackers based on predictive block matching
      in terms of both reliability and accuracy. The quantitative features selected
      from motion-strength and motor-activity signals constitute a satisfactory
      representation of neonatal seizures and random infant movements and seem to be
      complementary. Such features lead to trained neural networks that exhibit
      performance levels exceeding the initial goals of this study, the sensitivity
      goal being >or=80% and the specificity goal being >or=90%. CONCLUSIONS: The
      outcome of this experimental study provides strong evidence that it is feasible
      to develop an automated system for the recognition and characterization of the
      types of neonatal seizures based on video recordings. This will be accomplished
      by enhancing the accuracy and improving the reliability of the computational
      tools and methods developed during the course of the study outlined here.

PMID- 15946331
TI  - Epilepsy in young adults with autism: a prospective population-based follow-up
      study of 120 individuals diagnosed in childhood.
AB  - PURPOSE: Little is known about the long-term outcome of epilepsy in autism and
      the epilepsy characteristics of adults with autism. This prospective population
      based study was conducted in an attempt to point out differences on a group basis
      between adults with autism with or without epilepsy, and to describe the
      occurrence, the seizure characteristics, and the outcome of epilepsy in autism.
      METHODS: One hundred eight of 120 individuals with autism diagnosed in childhood
      and followed up prospectively for a period of 13-22 years were reevaluated at
      ages 17-40 years. As adults, the majority had mental retardation and autistic
      disorder or autistic-like condition. Interviews were performed with the
      caretakers of 42 of 43 individuals with a history of epilepsy, and their medical
      records were reviewed. RESULTS: Adults with autism and mental retardation
      constituted a severely disabled group. On a group basis, both the cognitive level
      and the adaptive behavior level were lower in the epilepsy group than in the
      nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy
      onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures
      with or without secondarily generalized seizures were the dominating seizure
      type. CONCLUSIONS: In a community sample of individuals with autism followed up
      from childhood through to adult age, one of three had epilepsy since
      childhood/adolescence. Severe mental retardation and autism are significantly
      associated with epilepsy, especially in female patients. Seizure frequency has a
      great impact on the individuals' lives. Specialist medical care is needed in this
      severely communication-disabled population.

PMID- 15946332
TI  - The neuropsychological and language profile of children with benign rolandic
      epilepsy.
AB  - PURPOSE: Benign rolandic epilepsy (BRE) has an excellent prognosis for seizures,
      but recent research has raised concerns using cognition as an outcome measure.
      Methodologic problems related to recruitment bias and assessment processes are
      evident in previous studies. With well-defined criteria for inclusion and
      comprehensive assessment, the aim of this study was to define the cognitive
      profile of children with BRE and to assess the effect of interictal EEG activity.
      METHODS: Patients (n=42) were recruited from six EEG laboratories. The EEG
      features analyzed were spike frequency, trains, and laterality. Comprehensive
      neuropsychological and language assessments were conducted. Group means on
      cognitive measures were compared with normative means. Tests were correlated with
      EEG features. RESULTS: The study demonstrated that children with BRE have normal
      intelligence and language ability. However, a specific pattern of difficulties in
      memory and phonologic awareness was found. Furthermore, a large proportion of
      children had disproportionate scores in these areas compared with intellectual
      and language ability. EEG features were minimally associated with cognitive
      difficulties, and no correlation was found with memory indices and tests of
      phonologic awareness. CONCLUSIONS: Some children with BRE have specific
      difficulties in memory and phonologic processing skills, not explained by
      interictal activity. We recommend that pediatricians ask about academic
      performance specifically in areas of prereading, reading, spelling, and memory.
      If difficulties are suspected, assessment targeting phonologic awareness and
      memory are recommended, as they may not be reflected in overall intellectual and
      language ability. Difficulties in phonologic awareness affect literacy, and
      memory problems affect academic performance.

PMID- 15946333
TI  - GABA receptor 1 polymorphism (G1465A) and temporal lobe epilepsy.
AB  - PURPOSE: To reevaluate the genetic contribution of the polymorphism G1465A of the
      gene coding for gamma-aminobutyric acid (GABA)(B) receptor 1 subunit [GABA(B)(1)]
      in a sample of French patients with temporal lobe epilepsy (TLE) and to perform
      an exploratory analysis in other phenotypic subgroups. METHODS: The 134 patients
      were genotyped for the polymorphism G1465A. This sample was divided in two
      groups. The first one had patients with nonlesional TLE, and the second one, with
      lesional TLE. Then these two groups were compared with a sample of 145 healthy
      individuals. RESULTS: The genotype and allele distributions for the polymorphism
      G1465A showed no difference between patients and controls. CONCLUSIONS: The
      association between the variant G1465A and the sample of patients could not be
      replicated, so these results exclude a major effect of this polymorphism in the
      susceptibility to nonlesional TLE. Larger samples should be tested to determine
      whether the G1465A in exon 7 of the GABA(B)(1) receptor gene is a susceptibility
      factor for nonlesional TLE.

PMID- 15946334
TI  - Spontaneous epileptic rats show changes in sleep architecture and hypothalamic
      pathology.
AB  - PURPOSE: The goal of the present study was to investigate the relationship
      between sleep, hypothalamic pathology, and seizures in spontaneous epileptic
      rats. METHODS: Rats were implanted with radiotelemetry transmitters for measuring
      electrocorticogram (ECoG) and stimulation electrodes in the hippocampus.
      Epileptogenesis was triggered by 2 h of electical stimulation-induced self
      sustained status epilepticus (SSSE). After SSSE, ECoGs were monitored over a 15
      week period for the occurrence of interictal high-amplitude low-frequency (HALF)
      acitvity and spontaneous reoccurring seizures (SRSs). RESULTS: Spontaneous
      epileptic rats showed clinical features of temporal lobe epilepsy (TLE), such as
      spontaneous seizures, interictal activity and neuronal cell loss in the
      dorsomedial hypothalamus, a region important for normal sleep regulation.
      Interestingly, epileptic rats showed disturbances in sleep architecture, with a
      high percentage of the seizures occurring during sleep. CONCLUSIONS: Therefore we
      conclude that a close association exists between epileptiform activity and
      alterations in sleep architecture that may be related to hypothalamic pathology.

PMID- 15946335
TI  - Hippocampal malformations do not necessarily evolve into hippocampal sclerosis.
AB  - PURPOSE: Hippocampal malformations have been proposed to underlie or evolve into
      hippocampal sclerosis, a common cause of refractory partial epilepsy. We report
      two patients with chronic epilepsy and developmental abnormalities of the
      hippocampus and cortex. We seek to address, in patients with recurrent convulsive
      seizures over many decades, whether hippocampal malformations necessarily
      progress to hippocampal sclerosis. METHODS: The first patient died at age 76
      years and had experienced convulsive seizures for 43 years. The second patient,
      aged 64 years at death, had experienced convulsive seizures for 49 years. The
      brains were processed routinely. Immunohistochemistry for dynorphin and
      neuropeptide Y was performed. RESULTS: The first case exhibited bilateral
      perisylvian polymicrogyria. Both hippocampi demonstrated abnormal convolution in
      the CA1 subfield and subiculum. In the second case, periventricular heterotopia
      was found in the wall of the right lateral ventricle. The right hippocampus was
      abnormally oriented with excessive convolutions of the pyramidal cell layer
      between CA1 and the subiculum. In neither patient did the hippocampi exhibit
      neuronal loss. Furthermore, dynorphin immunohistochemistry revealed no reactivity
      in the molecular layers, and staining with neuropeptide Y confirmed normal
      numbers of hilar interneurons. CONCLUSIONS: These two cases demonstrate
      histologically that, even in long-standing epilepsy, malformations of the
      hippocampus do not necessarily develop into hippocampal sclerosis.

PMID- 15946336
TI  - Periventricular white matter flumazenil binding and postoperative outcome in
      hippocampal sclerosis.
AB  - PURPOSE: In patients with hippocampal sclerosis (HS), anterior temporal lobe
      resection offers the possibility of a long-lasting suppression of seizures in two
      thirds of patients. White matter (WM) [11C]flumazenil volume of distribution (FMZ
      Vd) reflects the number of neuronal cell bodies in WM. Our objective was to
      correlate WM FMZ-Vd in patients with unilateral HS and postsurgical outcome.
      METHODS: We performed [11C]FMZ-PET in 15 patients with refractory mesial temporal
      lobe epilepsy (mTLE) and a quantitative MRI diagnosis of unilateral HS
      subsequently histologically verified in all cases. Median follow-up was 7 years
      (range, 6-9 years). Metabolite-corrected arterial plasma input functions and
      spectral analysis were used to generate parametric images of [11C]FMZ-Vd.
      Statistical parametric mapping (SPM99) with explicit masking was used to
      investigate the entire brain volume including WM. RESULTS: Eight patients had
      Engel class IA outcome (completely seizure free since surgery), and seven were
      not seizure free. Comparison of seizure-free patients with those who continued to
      have seizures after surgery revealed areas of increased FMZ binding around the
      posterior horns of the ipsilateral (z=3.7) and contralateral (z=2.7) ventricles
      in those with suboptimal outcomes. CONCLUSIONS: Preoperative [11C]FMZ-PET can
      detect periventricular increases of WM FMZ binding, implying heterotopic neurons
      in WM, in patients with mTLE. The presence of such increases correlates with a
      poorer outcome.

PMID- 15946337
TI  - Successful initiation of combined therapy with valproate sodium injection and
      divalproex sodium extended-release tablets in the epilepsy monitoring unit.
AB  - PURPOSE: Patients in epilepsy monitoring units (EMUs) often require aggressive
      initiation or reinitiation of therapy before discharge. We developed a simple
      dosing scheme using valproate sodium injection (VPA-IV) and divalproex sodium
      extended-release (VPA-ER) tablets to minimize the time required for initiation of
      therapy, without increasing the likelihood of seizures and adverse effects.
      METHODS: We identified 42 patients in the EMU, naive to VPA-IV and VPA-ER, for
      whom one of the discharge AEDs included divalproex sodium. On the day of
      discharge, patients were loaded with 20 mg/kg VPA-IV at 6 mg/kg/min, followed by
      approximately 20 mg/kg VPA-ER within 1 h. The discharge daily dose of VPA-ER was
      identical to the dose given after the IV load. We assessed tolerability and
      seizure occurrence during infusion, at 1 h, 4 h, and 1 week after discharge.
      RESULTS: All patients tolerated the VPA-IV dose followed by VPA-ER. Four patients
      reported mild nausea, and two patients reported mild dizziness within 4 h. No
      seizures or significant changes in heart rate or blood pressure occurred within 4
      h, and all patients were discharged the same day. All patients denied systemic
      complaints at 1 week, and five had seizures during the week after discharge. All
      patients had improved seizure frequencies at the end of the first week.
      CONCLUSIONS: VPA-IV is well tolerated and convenient for rapid loading in the
      EMU. When promptly followed by VPA-ER, seizure control remains excellent.

PMID- 15946338
TI  - Nonfebrile illness seizures: a unique seizure category?
AB  - PURPOSE: To describe the clinical characteristics of children with a first-time
      nonfebrile seizure in the setting of mild illness and to test the hypothesis that
      these seizures are associated with illness characterized by diarrhea. METHODS:
      This retrospective cohort study was performed in a pediatric emergency
      department. Patients ages 6 months to 6 years who were evaluated with first-time
      seizures were eligible for inclusion. Subjects were divided into three groups on
      the basis of symptoms accompanying their seizure: febrile (temperature, >38.0
      degrees C with seizure), unprovoked (no symptoms of illness), and nonfebrile
      illness (no fever at the time of seizure, but other symptoms of illness present).
      RESULTS: Of the 323 children with first-time seizures, 247 (76%) had febrile
      seizure, 37 (12%) had unprovoked seizures, and 39 (12%) had nonfebrile illness
      seizures. Children with nonfebrile illness seizures were more likely than
      children with febrile seizures to have diarrheal illnesses accompanying their
      seizure (44 vs. 16%; p=0.001). Frequency of cough, rhinorrhea, and rash did not
      differ significantly between children with febrile and nonfebrile illness
      seizures. Diagnostic testing for infectious etiologies was not performed
      frequently in either group. CONCLUSIONS: Nonfebrile illness seizures may
      represent a distinct group of seizures with unique epidemiology. Further study to
      define this seizure group better is warranted.

PMID- 15946340
TI  - First epileptic seizure induced by occupational nickel poisoning.
AB  - Toxic causes of seizures are numerous: alcohol and other substances of abuse,
      drugs, and industrial and household products. However, in the absence of a
      clearly suggestive history and/or associated symptoms and signs, identification
      of the toxic origin of new-onset seizures may be extremely difficult. We report
      here the case of a patient admitted in our hospital after a single generalized
      tonic-clonic seizure. The remarkable coincidence that a colleague of his, with
      whom he was working to clean the same workshop, had been admitted 1 week earlier
      for respiratory distress, coma, and de novo nonconvulsive focal status
      epilepticus, led us to consider a possible toxicologic etiology. Urine analysis
      revealed a high nickel concentration, suggestive of acute nickel poisoning.

PMID- 15946339
TI  - Gender differences in epilepsy.
AB  - PURPOSE: The aim of this study was to look at gender differences in unselected
      populations of patients with epilepsy classified according to the 1989
      International League Against Epilepsy (ILAE) criteria. METHODS: Data were
      obtained from two sources: (a) the EpiBase database at the outpatient clinic at
      the Department of Neurology, Aarhus University Hospital, Denmark, confined to
      adults with epilepsy (n=2,170), and (b) the Danish Twin Registry (n=318).
      RESULTS: In localization-related epilepsy, no overall gender difference was found
      in either the EpiBase population (n=1,511; w=750 (50%), m=761 (50%); p=0.80) or
      in the twin population (n=172; w=86 (50%), m=86 (50%); p=1.00). However, in the
      EpiBase population, localization-related symptomatic epilepsies were more
      frequent in men (n=939; w=426 (45%), m=513 (55%); p=0.005); and cryptogenic
      localization-related epilepsies were more frequent in women (n=572; w=324 (57%),
      m=248 (43%); p=0.002). In generalized epilepsy, more women than men were
      diagnosed in both populations [EpiBase: n=480, w=280 (58%), m=200 (42%); p<0.001;
      twin population: n=105, w=63 (60%), m=42 (40%); p=0.05]. The difference was
      confined to idiopathic generalized epilepsy [EpiBase: n=437, w=259 (59%), m=178
      (41%); p<0.001; twin population: n=94, w=60 (64%), m=34 (36%); p=0.01].
      CONCLUSIONS: More women than men were diagnosed with idiopathic generalized
      epilepsy in two epilepsy populations. Overall, no gender difference was found in
      localization-related epilepsy, but localization-related symptomatic epilepsies
      were more frequent in men, and cryptogenic localization-related epilepsies were
      more frequent in women The results suggest a gender susceptibility to the
      development of specific epilepsy subtypes.

PMID- 15946341
TI  - Speech-induced aphasic seizures in epilepsy caused by LGI1 mutation.
AB  - PURPOSE: Patients with autosomal dominant lateral temporal lobe epilepsy (ADTLE)
      may have seizures precipitated by sound or speech. We have examined a patient
      with speech-induced seizures caused by an LGI1 mutation (C46R). METHODS: A
      clinical study and a video-EEG recording using interrogative speech as the
      activation procedure was performed in a 23-year-old man. RESULTS: He had
      experienced short episodes of sensory aphasia in situations in which he was
      suddenly verbally addressed. Voices became distorted, and he could not comprehend
      despite hearing words. The day after a late party, his girlfriend unexpectedly
      spoke to him. Her speech became unintelligible to him. He did not reply and had a
      generalized tonic-clonic (GTC) seizure. During an EEG, he was suddenly asked for
      the names of his siblings. He answered, but lost understanding of the further
      conversation and described how syllables floated together with an echoing
      character. With a versive movement to the right, another GTC occurred. In the
      EEG, rhythmic 6-Hz activity built up in the frontotemporal areas starting on the
      left side with bilateral and posterior spreading. Postictal slowing was
      symmetrical, and no aphasia was noted on awakening. CONCLUSIONS: To our
      knowledge, this is the first video-EEG recorded seizure in LGI1-caused ADTLE.
      This peculiar seizure semiology and precipitating effect of speech may serve as a
      marker for identifying further individuals with this particular phenotype and
      genotype and may indicate that the LGI1 gene may have a physiologic function
      connected to the human capacity for speech and language.

PMID- 15946342
TI  - Calcium-channel blocker verapamil administration in prolonged and refractory
      status epilepticus.
AB  - We report on an 11-year healthy boy who presented refractory status epilepticus
      (SE), which was unresponsive to conventional antiepileptic drugs used in the
      algorithm of the treatment of SE. Based on evidence that verapamil has
      anticonvulsant activity in animal models and the fact that the boy had a
      supraventricular tachycardia (140-160 b/min), i.v. verapamil (0.034 mg/min) was
      administered on day 37, and after a 3.125 mg cumulative verapamil dose (1.5 hour
      after initiation of the infusion), the patient regained consciousness was able to
      breathe spontaneously and the electrical SE promptly disappeared. The apparent
      dramatic response to i.v. verapamil may be explained by its direct anticonvulsant
      action on the basis of the potential involvement of calcium channels in epileptic
      activity and that verapamil, a known Pgp inhibitor in the cerebrovascular
      endothelium in the epilepticus focus, acted by facilitating the brain penetration
      of the antiepileptic drugs that our patient was receiving simultaneously.

PMID- 15946343
TI  - Serum valproate levels with oral contraceptive use.

PMID- 15946344
TI  - Hyponatremia associated with repeated use of levetiracetam.
AB  - Levetiracetam (LEV) is increasingly used as adjunctive anticonvulsant therapy
      because of apparent low toxicity. Somnolence, asthenia, headache, dizziness, and
      nervousness are the most frequently reported side effects (1). We describe a
      patient, predisposed to the development of the syndrome of inappropriate
      antidiuretic hormone secretion (SIADH), in whom hyponatremia developed after two
      challenges of LEV.

PMID- 15946345
TI  - Partial seizure provoked by hyperbaric oxygen therapy: possible mechanisms and
      implications.
AB  - Hyperbaric oxygen treatment (HBO2) is used commonly for treatment of bone and
      soft-tissue radiation necrosis. It may be a potential therapy for radiation
      necrosis seen after brain irradiation. HBO2 risks include generalized tonic
      clonic convulsions. We report a patient after resection of anaplastic astrocytoma
      and 5,580 cGy of total external-beam radiation treatments with brain radiation
      necrosis who underwent HBO2 therapy and developed a partial seizure during
      treatment. Mechanisms and implications are discussed.

PMID- 15946346
TI  - Gaze deviation from contralateral pseudoperiodic lateralized epileptiform
      discharges (PLEDs).
AB  - Pseudoperiodic lateralized epileptiform discharges (PLEDs) usually produce
      "negative" neurologic findings. This contrasts with seizures which typically
      induce cortical activation with "positive" clinical manifestations. Gaze
      preference may arise from ipsilateral frontal eye fields (FEFs) damage because of
      the unopposed action of an intact contralateral FEF. Epileptic nystagmus (EN) and
      gaze deviation (GD) can also occur with focal temporo-parieto-occipital or
      hemispheric seizures in awake or obtunded patients. A patient with old right
      frontal and parieto-temporal cerebral infarctions manifested leftward gaze
      preference and deviation (without nystagmus) while alert and talking. Digitized
      EEG demonstrated PLEDs at approximately 1 Hz over the right fronto-central
      region, without electrographic seizures. This report illustrates that PLEDs
      without seizures may excite frontal regions proximate to the FEFs to produce
      contraversive gaze preference in an awake patient, and discusses putative
      mechanisms. Gaze deviation, in this case, was the principal clinical feature of
      PLEDs.

PMID- 15946347
TI  - Epilepsies after Pocket Monster seizures.
AB  - BACKGROUND: We conducted a 5-year follow-up study in patients with a seizure
      induced by animated cartoon "Pocket Monster." METHODS: A recurrence of seizures
      was observed in 25 of 91 patients with a Pocket Monster seizure. The patients
      were divided into two groups: Epilepsy group of 12 patients with a history of
      epilepsy and Nonepilepsy group of 13 patients without a history of epilepsy.
      RESULTS: Age below 12 years and generalized seizures were more often in
      Nonepilepsy group than in Epilepsy group. Seizure recurrence was earlier in
      Epilepsy group than in Nonepilepsy group. Photoparoxysmal response was relatively
      infrequent in Epilepsy group. The majority of patients were classified into
      idiopathic generalized epilepsies in Nonepilepsy group, whereas most patients
      were categorized into localization-related epilepsies in Epilepsy group.
      CONCLUSIONS: Epilepsies after Pocket Monster seizures were different according to
      the presence or absence of a history of epilepsy. These results will be useful in
      order to determine the treatment of a patient with a visually induced seizure.

PMID- 15946349
TI  - Intracardiac ultrasound detection of thrombus on transseptal sheath: incidence,
      treatment, and prevention.
AB  - BACKGROUND: Transseptal (TS) catheterization is used for left atrial (LA)
      ablation procedures and a major risk is thromboembolism. The purpose of this
      study was to assess (1) the value of intracardiac ultrasound (ICUS) monitoring
      during LA ablation procedures, and (2) a new technique to reduce the risk of
      thrombus formation. METHODS AND RESULTS: One hundred and eighty consecutive
      patients underwent TS catheterization under ICUS guidance with two sheaths for
      atrial fibrillation ablation and one for other LA procedures. Group I included
      the initial 90 patients in whom TS sheaths were flushed with a standard 2 U/cc
      concentration of heparin; group II consisted of the next 90 patients in whom
      sheaths were flushed with 1,000 U/cc concentration. All patients received bolus
      and infusion of heparin to maintain ACT between 250-300 seconds. ICUS was
      monitored throughout. In group I, echodense material at the tip of the sheath
      consistent with thrombus was observed on ICUS in 8 of 90 patients (9%) within 5
      15 minutes of entering the LA. In group II, only 1 of 90 patient (1%)
      demonstrated thrombus (P < 0.001). There were no significant clinical differences
      in group I patients with and without thrombus. In all nine patients, the clot was
      removed with vigorous aspiration. No patients suffered a neurological event.
      CONCLUSION: Thrombus formation on TS sheath, detected by ICUS, may be more common
      than expected despite adequate anticoagulation. Using a higher concentration of
      heparin for the TS system before deployment reduced the risk. The thrombus was
      retrieved with aspiration without the need to abort the procedure.

PMID- 15946350
TI  - How do we get there from here-is it safe and in whose hands?

PMID- 15946351
TI  - Superior vena cava flutter: electrophysiology and ablation.
AB  - INTRODUCTION: Reentry within a major thoracic vein has been suggested as a cause
      of atrial arrhythmias. However, little is known about these potential reentrant
      circuits. METHODS AND RESULTS: Atypical atrial flutter was induced and mapped in
      67 out of 225 atrial flutter ablation procedures. Reentry around the superior
      vena cava (SVC) was suspected in three patients. The suspected SVC flutter was
      induced and terminated by pacing in all patients. Fusion was demonstrated during
      flutter entrainment by subeustachian isthmus pacing in all of them. The
      postpacing interval following entrainment by pacing from different sites of the
      right atrium (RA) or coronary sinus was longer than the flutter cycle length.
      Macroreentry within the SVC was demonstrated both by sequential activation and a
      postpacing interval matching the flutter cycle length when pacing from different
      sites around the SVC in all patients. Atrial-venous-atrial electrogram sequence
      was demonstrated following flutter entrainment by atrial pacing. Flutter was
      terminated by an electrical stimulus delivered to the SVC, which was not
      propagated to the trabeculated RA, in one patient, and linear radiofrequency
      application from the distal SVC to the posterior wall of the RA, or to the
      superoseptal portion of the crista terminalis, in the other two. CONCLUSION:
      Macroreentry within the SVC is a distinctive mechanism responsible for rapid
      atrial activation, which is different from other reported flutter mechanisms,
      such as upper loop reentry. SVC longitudinal radiofrequency application can
      eliminate the arrhythmia without the need for complete electrical disconnection
      of the vein.

PMID- 15946352
TI  - Embolic events and char formation during pulmonary vein isolation in patients
      with atrial fibrillation: impact of different anticoagulation regimens and
      importance of intracardiac echo imaging.
AB  - Thromboembolic events are important complications of pulmonary vein isolation
      (PVI) procedures, occurring in up to 2.8% of patients. In this study, we report
      the incidence of char formation and embolic events with different anticoagulation
      protocols prospectively changed to reduce such complication. METHODS: A total of
      785 patients (mean age: 54 years, 83.5% male) underwent catheter-based PVI for
      treatment of drug refractory, symptomatic atrial fibrillation (AF). PVI was
      performed utilizing different strategies including radiofrequency (RF) using
      temperature control energy delivery and RF using intracardiac echocardiography
      (ICE)-guided power titration. Patients were divided based on the anticoagulation
      protocol into three groups: in group 1 (194 patients), activation coagulation
      time (ACT) was maintained between 250 and 300 seconds; in group 2 (180 patients),
      ACT was maintained between 300 and 350 seconds plus the IV infusion of
      eptifibatide (135 microg/kg bolus + 0.5 microg/kg/min); and in group 3 (411
      patients), ACT was maintained between 350 and 400 seconds. RESULTS: Char
      formation was detected in 69 patients of group 1, 5 of group 2, and 8 of group 3.
      An embolic event was observed in 7 patients of group 1, 3 of group 2, and 2 of
      group 3 (P = 0.01; group 1 vs group 3). Higher degree of anticoagulation with
      heparin was associated with a reduced incidence of embolic events even after
      removing the patients undergoing ICE-guided ablation (P = 0.04). CONCLUSION: More
      aggressive anticoagulation with heparin reduced periprocedural embolic events.
      The use of platelet inhibition does not have incremental beneficial effect. None
      of the anticoagulation protocol abolished char formation.

PMID- 15946353
TI  - Changes of pulmonary vein orifice size and location throughout the cardiac cycle:
      dynamic analysis using magnetic resonance cine imaging.
AB  - INTRODUCTION: Anatomically guided left atrial ablation is used increasingly for
      treatment of atrial fibrillation (AF). Three-dimensional mapping systems used for
      pulmonary veins (PV) encircling ablation procedures anticipate a stable size and
      position of the PV orifice. The aim of the current study was therefore to analyze
      changes of PV orifice size and location throughout the cardiac cycle using cine
      magnetic resonance imaging (MRI). METHODS AND RESULTS: Twenty-five healthy
      volunteers were studied using a 1.5 Tesla MRI system. MR angiograms were acquired
      with a breath-hold three-dimensional fast-spoiled gradient-echo imaging (3D
      FSPGR) sequence in the coronal plane before and after gadolinium injection.
      Maximum intensity projections and multiplanar reformations were performed to
      reconstruct images of the PV. Bright blood cine imaging in the axial view was
      acquired by a steady-state free precession pulse sequence. Twenty bright blood
      images were obtained per cardiac cycle. The axial (anterior-posterior) PV orifice
      diameter was measured in all 20 images. For analysis of PV movement the location
      of the orifice posterior edge was plotted on scale paper. PV orifice size depends
      on the stage of the cardiac cycle with the largest diameter in late atrial
      diastole and a mean decrease of 32.5% during atrial systole. Location changes of
      the PV orifice are in the range of up to 7.2 mm and larger in the coronal
      (lateral-medial) than in the sagittal (anterior-posterior) direction. CONCLUSION:
      PV orifice size and location is not as stable as anticipated by three-dimensional
      mapping systems used for PV encircling left atrial ablation procedures. RF
      application close to the presumed orifice location should therefore be avoided to
      minimize the risk of PV stenosis.

PMID- 15946354
TI  - Esophageal temperature monitoring during radiofrequency ablation of atrial
      fibrillation.
AB  - INTRODUCTION: Ablative strategies for atrial fibrillation have centered on the
      left atrium, in particular the pulmonary veins. An emphasis on ablating outside
      the ostia of the pulmonary veins appears to have reduced the risk of pulmonary
      vein stenosis. Unfortunately, ablation in the posterior left atrium has been
      reported to result in fatal atrio-esophageal fistula. METHODS AND RESULTS: We
      monitored esophageal temperatures in 16 consecutive patients undergoing atrial
      fibrillation ablation. There were 14 men and 2 women; average age 54.7 +/- 10.6
      years. Eight patients had a lasso-guided pulmonary isolation procedure, eight an
      electroanatomically guided left-atrial circumferential approach. A commercially
      available esophageal temperature probe (Mallinckrodt Mon-a-therm 12F Esophageal
      Stethoscope with Temperature Sensor, Thermistor 400 Series) was positioned under
      general anesthesia. Temperature changes were noted and related to the relative
      location of the ablation catheter and the temperature probe during the
      temperature change. The esophagus was midline in three, right sided in three, and
      left sided in the remaining patients. Temperature rises could be recorded at the
      posterior aspect of any pulmonary vein. Detailed analysis of six patient maps
      revealed heating occurred with lesions created within 1 cm of the esophagus.
      CONCLUSION: The location of the esophagus relative to the back of the left atrium
      displays considerable variability. It is rarely midline and most often lies in
      close proximity to the left-sided veins. Ablation in close radiographic proximity
      (approximately 1 cm) to the esophagus as defined by a radio-opaque temperature
      probe can result in heating at the esophageal lumen.

PMID- 15946355
TI  - Simultaneous dual fast and slow pathway conduction upon induction of typical
      atrioventricular nodal reentrant tachycardia: electrophysiologic characteristics
      in a series of patients.
AB  - INTRODUCTION: Simultaneous dual atrioventricular nodal conduction (SDNC) through
      slow (SP) and fast pathway (FP) is a rare phenomenon observed upon the induction
      of atrioventricular nodal reciprocating tachycardia (AVNRT). The aim of this
      study is to report the electrophysiological features of patients showing typical
      AVNRT induced through SDNC. METHODS AND RESULTS: Among 461 consecutive patients
      with typical AVNRT submitted to radiofrequency catheter ablation (RFCA), seven
      patients (1.5%) with SDNC at tachycardia onset (group I: 6 female; age 60-72
      years, mean 65.2 +/- 3.8 years) and 118 age-matched controls (group II: 60
      female; age 60-88 years, mean 68.4 +/- 6.8 years) were considered. Controls were
      further subdivided into two subgroups according to age: subgroup A (94 patients,
      age 60-75 years) and subgroup B (24 patients, age >75 years). The value of the
      following parameters was significantly higher in group I than in group II and in
      subgroup A: A-H interval [113 +/- 26 vs. 89 +/- 27 (P < 0.01) vs. 84 +/- 19 (P <
      0.001)], ventriculoatrial conduction effective refractory period [355 +/- 85 vs.
      293 +/- 87 (P < 0.05) vs. 281 +/- 82 (P < 0.05)], SP conduction time upon AVNRT
      induction [444 +/- 104 vs. 350 +/- 72 (P < 0.01); vs. 345 +/- 67 (P < 0.001)],
      AVNRT cycle length [484 +/- 103 vs. 396 +/- 71 ms (P < 0.05); vs. 384 +/- 69 (P <
      0.05)], and rate of AVNRT induction from ventricle [71% vs. 10% (P = 0.001); vs.
      6% (P = 0.001)]. Differences were mostly not significant between group I and
      subgroup B. SP location and RFCA success rate were similar in all groups.
      CONCLUSION: In a population of AVNRT patients, SDNC at AVNRT induction is
      infrequent and it prevails beyond the fifth decade of life and in females. SDNC
      is associated with peculiar AVN conduction features, which resemble the age
      related modifications of AVN conduction.

PMID- 15946356
TI  - Atrial response to ventricular antitachycardia pacing discriminates mechanism of
      1:1 atrioventricular tachycardia.
AB  - BACKGROUND: Inappropriate shocks from implantable cardioverter defibrillators
      (ICD) remain a significant clinical problem despite device discrimination
      algorithms. The atrial response to antitachycardia pacing (ATP) may determine the
      mechanism of 1:1 A:V tachycardia. METHODS: For this study we refer to sinus
      tachycardia, atrial tachycardia (AT), atrial fibrillation, and flutter as atrial
      tachycardia (AT), and all other tachycardia as "non-AT." Three atrial response
      patterns during the burst of ATP were determined. The atrial cycle length (ACL)
      may be unchanged (type 1) indicating AT. The ACL may show variation during ATP
      (type 2) indicating variable VA block and does not discriminate between an AT and
      a non-AT mechanism, in which case a default diagnosis of non-AT is made. The ACL
      may accelerate to the ATP cycle length (type 3) indicating entrainment. A VAAV
      response at the end of ATP was considered diagnostic of AT (type 3A) whereas a
      VAV or VVA response was considered a non-AT mechanism (type 3B). This algorithm
      was applied to ICD tracings from 68 episodes of spontaneous 1:1 A:V tachycardia
      that had 136 sequences of ATP administered. The rhythm "truth" was determined by
      consensus of two experienced clinicians. RESULTS: The algorithm correctly
      identified AT with a sensitivity of 71.9% (95% CI: 67.1-73.6), and specificity of
      95% (83.5-99.1). The PPV was 97.2% (90.9-99.5), and NPV 58.5% (51.4-61.0). Kappa
      was 0.57 (0.43-0.62). If used clinically the algorithm would have aborted 53.3%
      (8/15) of inappropriate shocks delivered into an AT-mechanism tachycardia and
      would not have withheld a shock for any episode of VT. CONCLUSION: Analysis of
      atrial response patterns during and after ventricular ATP can successfully
      discriminate tachycardia mechanism and may reduce inappropriate ICD shocks.

PMID- 15946357
TI  - Deductive electrophysiology in the modern device technology era: the quest for
      the prevention of inappropriate ICD shocks.

PMID- 15946358
TI  - Efficacy and safety of radiofrequency catheter ablation of atrioventricular nodal
      reentrant tachycardia in the elderly.
AB  - INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most
      common regular supraventricular tachycardia in the general population as well as
      in elderly patients. The purpose of the study was to investigate the success and
      complication rate particularly regarding the induction of an atrioventricular
      (AV) block by radiofrequency (RF) ablation in elderly patients with and without a
      preexisting AV block. METHODS AND RESULTS: Between February 1998 and July 2004,
      all patients with symptomatic AVNRT referred for slow-pathway ablation in our
      institution were included and divided into two groups: group 1 patients younger
      than 75 years (n = 508) and group 2 patients > or =75 years (n = 70). A
      preexisting prolonged PR interval was present in 17 (3.3%) patients of group 1
      and in 26 (37%, P < 0.0001) patients of group 2. Following successful slow
      pathway ablation (follow-up time group 1: 37 +/- 22, group 2: 37 +/- 24 months)
      no induction of an AV block was observed in group 2 but in four patients of group
      1 (0.79%) a complete heart block was induced requiring a pacemaker implantation.
      In group 1, 15 (2.95%) patients with a recurrence of AVNRT were readmitted for a
      repeat ablation procedure. No recurrences occurred in group 2. CONCLUSION:
      Despite a higher incidence of preexisting prolonged PR intervals slow-pathway
      ablation in elderly patients is both effective and safe and should be considered
      as the first line therapy also in this patient population.

PMID- 15946359
TI  - Effects of cardiac resynchronization therapy on ventricular repolarization in
      patients with congestive heart failure.
AB  - INTRODUCTION: Biventricular pacing has been shown to improve the clinical status
      of patients with congestive heart failure, but little is known about its
      influence on ventricular repolarization. The aim of our study was to evaluate the
      effect of biventricular pacing on ECG markers of ventricular repolarization in
      patients with congestive heart failure. METHODS AND RESULTS: Twenty-five patients
      with congestive heart failure, sinus rhythm (SR), and complete LBBB (6 females;
      age 61 +/- 8 years; NYHA class II-III; echocardiographic ejection fraction 21 +/-
      5%; QRS > or = 130 ms) underwent permanent biventricular DDDR pacemaker
      implantation. A high-resolution 65-lead body-surface ECG recording was performed
      at baseline and during right-, left-, and biventricular pacing, and the total 65
      lead root mean square curve of the QRST complex and the interlead QT dispersion
      were assessed. The QRS duration was increased during right (RV)- and left
      ventricular (LV) pacing (127 +/- 26% and 117 +/- 40%; P < 0.05), as compared to
      SR (100%) and biventricular pacing (93 +/- 16%; ns). The QTc interval was
      increased during RV and LV pacing (112 +/- 12% and 114 +/- 14%; P < 0.05) as
      compared to SR (100%) or biventricular pacing (99 +/- 12%). There was no effect
      on JT interval during all pacing modes. The T(peak-end) interval was increased
      during right (120 +/- 34%; P < 0.01) and LV pacing (113 +/- 29%; P < 0.05) but
      decreased during biventricular pacing (81 +/- 19%; P < 0.01). A similar effect
      was found for the T(peak-end) integral and the T(peak) amplitude. QT dispersion
      was increased during right ventricular (129 +/- 16 ms; P < 0.05) and decreased
      during biventricular pacing (90 +/- 12 ms; P < 0.01), as compared to SR (114 +/-
      22 ms). CONCLUSIONS: Using a high-resolution surface ECG, biventricular pacing
      resulted in a significant reduction of ECG markers of ventricular dispersion of
      repolarization.

PMID- 15946360
TI  - Cardiac resynchronization therapy and the arrhythmogenic substrate.

PMID- 15946361
TI  - Quantitative assessment of microvolt T-wave alternans in patients with congestive
      heart failure.
AB  - INTRODUCTION: T-wave alternans has been shown to be linked to the genesis of
      ventricular tachyarrhythmias. Currently, only qualitative assessment of microvolt
      T-wave alternans (MTWA) is recommended in clinical practise. Whether quantitative
      assessment of MTWA yields complementary information is unknown. METHODS AND
      RESULTS: Noninvasive MTWA determination was performed in 204 consecutive patients
      with ischemic or nonischemic cardiomyopathy. Of those, 100 tested MTWA positive.
      In these recordings, MTWA magnitude was quantitatively assessed (alternans
      voltage, V(alt)). Patients were followed for a mean of 17 months. Ventricular
      tachyarrhythmic events constituted the study endpoint. Patients with nonischemic
      cardiomyopathy had a higher V(alt) than patients with ischemic cardiomyopathy
      (10.3 +/- 9.2 [median 7.2] vs 6.2 +/- 3.2 [median 4.6] microV; P = 0.007). The
      number of MTWA-positive ECG leads was also higher in patients nonischemic
      cardiomyopathy (7.3 +/- 2.4 [median 8] vs 6.0 +/- 2.5 [median 6]; P = 0.016).
      Patients who suffered an arrhythmic event during follow-up had higher MTWA
      voltages (10.8 +/- 10.0 [median 8.8] vs 7.4 +/- 5.7 [median 6.4] microV; P =
      0.05) a higher number of MTWA-positive ECG leads (7.6 +/- 2.4 [median 8] vs 6.4
      +/- 2.5 [median 6]; P = 0.05) compared to patients with an uncomplicated course.
      CONCLUSION: Patients with nonischemic cardiomyopathy and patients with
      tachyarrhythmic complications have more extensive MTWA possibly reflecting more
      extensive myocardial damage and a higher arrhythmia propensity.

PMID- 15946362
TI  - T-wave alternans: does size matter.

PMID- 15946363
TI  - Ventricular arrhythmias following exposure of failing hearts to oxidative stress
      in vitro.
AB  - INTRODUCTION: There is experimental evidence that heart failure (HF) is an
      oxidative stress and that HF myocytes may be damaged by oxygen-derived free
      radicals. However, the arrhythmogenicity of these radicals has not been studied
      in HF. METHODS AND RESULTS: Isolated perfused hearts were obtained from sham
      operated (SHAM, n = 6), and fast pacing (250 ms, 2 weeks)-induced heart failure
      porcines (HF, n = 8). Epicardial conduction was mapped in the longitudinal and
      transverse directions and ventricular arrhythmias were closely monitored after
      perfusion of 100, 300, and 1000 micromol/L H(2)O(2). Left ventricular epicardium
      was sampled for action potentials recordings in the same conditions. Myocardial
      levels of thiobarbituric acid reactive substances and antioxidant enzymatic
      capacity were also assessed. Epicardial conduction velocities were unaffected by
      H(2)O(2) in both groups. Isolated ventricular premature beats and runs of slow
      ventricular rhythm with H(2)O(2) more frequently occurred in HF compared to SHAM
      despite an increased antioxidant capacity including Cu/Zn and Mn superoxide
      dismutase, catalase, glutathione reductase, and glutathione peroxidase. Sustained
      arrhythmias were not observed. Higher thiobarbituric acid reactive substances
      levels were found in HF confirming endogenous oxidative stress. Action potential
      duration at plateau level was increased following H(2)O(2) in SHAM but not in HF
      epicardial fibers where a toxic effect developed at 1000 micromol/L. CONCLUSION:
      Oxidative stress with concomitant increase in antioxidant capacity develops in
      this HF model. There is a greater proclivity to oxidative stress-mediated
      arrhythmias in HF. These arrhythmias are mainly extrasystoles or slow ventricular
      rhythms and not dependent on abnormal myocardial conduction.

PMID- 15946364
TI  - Comment on "ventricular arrhythmias following exposure of failing hearts to
      oxidative stress in vitro".

PMID- 15946365
TI  - Role of repolarization restitution in the development of coarse and fine atrial
      fibrillation in the isolated canine right atria.
AB  - INTRODUCTION: Although the role of action potential duration restitution (APD-R)
      in the initiation and maintenance of ventricular fibrillation (VF) has been the
      subject of numerous investigations, its role in the generation of atrial
      fibrillation (AF) is less well studied. The cellular and ionic basis for coarse
      versus fine AF is not well delineated. METHODS AND RESULTS: We measured APD-R
      during acetylcholine-mediated AF as well as during pacing (standard and dynamic
      protocols) in crista teriminalis, pectinate muscle, superior vena cava, and
      appendage of isolated canine arterially perfused right atria (n = 15).
      Transmembrane action potential (TAP), pseudo-ECG, and isometric tension
      development were simultaneously recorded. Acetylcholine flattened APD-R measured
      by both standard and dynamic protocols, but promoted induction of AF. AF was
      initially coarse, converting to fine within 3-15 minutes of AF. Coarse, but not
      fine AF was associated with dramatic fluctuations in tension development,
      reflecting wide variations in intracellular calcium activity ([Ca(2+)](i)).
      During coarse AF, APD-R data displayed a cloud-like distribution pattern, with a
      wide range of maximum APD-R slope (from 1.21 to 0.35). A maximum APD-R slope >1
      was observed only in crista terminalis (3/10). The APD-R relationship was
      relatively linear and flat during fine AF. Reduction of [Ca(2+)](i) was
      associated with fine AF whereas augmentation of [Ca(2+)](i) with coarse AF.
      CONCLUSIONS: Our data indicate that while APD-R may have a limited role in the
      maintenance of coarse AF, it is unlikely to contribute to the maintenance of fine
      AF and that [Ca(2+)](i) dynamics determine the degree to which AF is coarse or
      fine.

PMID- 15946366
TI  - Ventricular tachycardia duration and form are associated with electrical
      discontinuities bounding the core of the reentrant circuit.
AB  - BACKGROUND: Successful prediction of reentrant ventricular tachycardia duration
      and form from sinus-rhythm electrogram signals in canine hearts is relevant to
      clinical studies, to potentially improve catheter ablation treatment during EP
      study. METHODS/RESULTS: Following LAD ligation of canine hearts, activation maps
      were constructed from 312 border zone sites 4-5 days postinfarction. When
      reentrant ventricular tachycardia was inducible via programmed stimulation, the
      core of the circuit was defined on the maps as the enclosed area formed by the
      adjoining lines of slowest conduction and block bounding the protected region of
      the reentrant circuit. The number, location, and width of points of entrance or
      exit of the activation wavefront about the core were determined. Core perimeter
      location was then marked on the sinus-rhythm activation map, and the difference
      in activation time at opposite recording sites along the core perimeter was
      measured. Mean sinus-rhythm activation was highly discontinuous along the core
      perimeter in 10 transient reentry experiments (30.1 +/- 4.4 ms), moderately
      discontinuous in 13 sustained experiments (16.7 +/- 1.8 ms), and only slightly
      discontinuous in 5 noninducible experiments (9.7 +/- 1.7 ms). For transient
      versus sustained experiments, the entrance/exit points were narrower (mean: 6.5
      +/- 1.0 mm vs 9.5 +/- 1.8 mm) with larger sinus-rhythm discontinuity across them
      (mean: 23.8 +/- 6.0 ms vs 11.8 +/- 2.1 ms). As core size increased, so did the
      number of entrance/exits present during reentry (P < 0.001). With increasing core
      size, four-loop (quatrefoil) reentry was frequently observed. CONCLUSIONS:
      Whether reentrant ventricular tachycardia will be inducible in the canine infarct
      border zone, and its duration and form, is associated with the characteristics of
      electrical discontinuities present about the core perimeter.

PMID- 15946367
TI  - Ventricular tachycardia induced by biventricular pacing in patient with severe
      ischemic cardiomyopathy.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) is a new alternative which
      affords symptomatic improvement in two-thirds of patients who exhibit medically
      refractory congestive heart failure (CHF) as well as significant prolongation of
      the QRS duration (>135 msec). As more experience with CRT accrues, unexpected
      complications of this promising therapy may become apparent. Herein, we describe
      a patient with severe ischemic cardiomyopathy and refractory CHF who developed
      incessant ventricular tachycardia (VT) after the initiation of biventricular
      pacing. The patient is a 75-year-old man who suffered an inferior myocardial
      infarction 6 years before presenting for CRT. He underwent a three-vessel CABG in
      1997. Subsequently, episodes of near syncopal sustained VT developed, for which
      he received a dual chamber ICD. In 2001 he developed refractory CHF and ECG
      revealed LBBB with a QRS duration of 195 msec. Shortly after the initiation of
      biventricular pacing, the patient developed multiple episodes of drug resistant
      monomorphic VT that could be terminated only transiently by ICD therapies.
      Ultimately, the only intervention, which proved to be effective in eliminating VT
      episodes, was inactivation of LV pacing. Despite subsequent therapeutic regimen
      of sotalol, lidocaine, tocainide, and quinidine all subsequent attempts to
      reactivate LV pacing resulted in prompt VT recurrence. CONCLUSION: This case
      represents a clear example of CRT induced proarrhythmia, which required
      inactivation of LV pacing for effective acute management. Such an intervention
      should be considered in CRT patients who exhibit a notable increase in drug
      refractory VT episodes.

PMID- 15946368
TI  - Remote catheter ablation of parahisian accessory pathways using a novel magnetic
      navigation system--a report of two cases.
AB  - INTRODUCTION: Ablation of anteroseptal (parahisian) pathways may be difficult
      using conventional catheters. METHODS AND RESULTS: Two patients (51 and 20 years
      old) underwent ablation of a parahisian accessory pathway using the magnetic
      navigation system Niobe (Stereotaxis, Inc.), which consists of two external
      permanent magnets (0.08 Tesla) that steer a small magnet embedded in the tip of
      the ablation catheter. A motor drive allows the advancement or retraction of the
      catheter. From the control room, the ablation was performed using a single
      radiofrequency current application (fluoroscopy 3.2 and 6.0 minutes,
      respectively). CONCLUSIONS: The Niobe magnetic navigation system was successfully
      used to perform completely remote controlled mapping and ablation of parahisian
      accessory pathways.

PMID- 15946369
TI  - Tachycardia with VA dissociation: an unusual tachycardia mechanism.

PMID- 15946370
TI  - An approach to noncavotricuspid isthmus dependent flutter.

PMID- 15946371
TI  - Suppression of electrical storm by oral quinidine in a patient with Brugada
      syndrome.

PMID- 15946372
TI  - Three-dimensional reconstruction of the coronary sinus using rotational
      angiography.

PMID- 15946374
TI  - Clinical assessment of antiarrhythmic agents for paroxysmal atrial fibrillation
      guided by modification of electrophysiologic arrhythmogenicity.

PMID- 15946376
TI  - Jumping in before the water is hot: the need to support randomized controlled
      clinical trials.

PMID- 15946378
TI  - Gender differences in electrophysiologic effects of mental stress and autonomic
      tone inhibition: a study in healthy individuals.

PMID- 15946379
TI  - Is the routine drainage after surgery for thyroid necessary? A prospective
      randomized clinical study [ISRCTN63623153].
AB  - BACKGROUND: Drains are usually left after thyroid surgery to prevent formation of
      hematoma and seroma in the thyroid bed. This is done to reduce complications and
      hospital stay. Objective evaluation of the amount collected in the thyroid bed by
      ultrasonography (USG) can help in assessing the role of drains. METHODS: A
      randomized prospective control study was conducted on 94 patients undergoing 102
      thyroid surgeries, over a period of fifteen months. Patients included in the
      study were randomly allocated to drain and non-drain group on the basis of
      computer generated random number table. The surgeon was informed of the group
      just before the closure of the wound Postoperatively USG neck was done on first
      and seventh postoperative day by the same ultrasonologist each time. Any
      swelling, change in voice, tetany and tingling sensation were also recorded. The
      data was analyzed using two-sample t-test for calculating unequal variance.
      RESULTS: Both groups were evenly balanced according to age, sex, and size of
      tumor, type of procedure performed and histopathological diagnosis. There was no
      significant difference in collection of thyroid bed assessed by USG on D1 & D7 in
      the two groups (p = 0.313) but the hospital stay was significantly reduced in the
      non-drain group (p = 0.007). One patient in the drain group required needle
      aspiration for collection in thyroid bed. No patient in either group required re
      operation for bleeding or haematoma. CONCLUSION: Routine drainage of thyroid bed
      following thyroid surgery may not be necessary. Not draining the wound results in
      lesser morbidity and decreased hospital stay.

PMID- 15946380
TI  - HER-2/neu and CD117 (c-kit) overexpression in patients with pesticide exposure
      and extensive stage small cell lung carcinoma (ESSCLC).
AB  - BACKGROUND: The rate of detection of HER-2/neu and CD117 (c-kit) overexpression
      in small cell lung cancer (SCLC) has varied widely; between 5-35% and 21-70%
      respectively. METHODS: To evaluate the relationship between pesticide exposure
      and HER-2/neu and CD117 overexpression in extensive stage SCLC (ESSCLC), we
      identified patients with ESSCLC and assessed pesticide exposure using a
      predetermined questionnaire. An exposure index (hours/day x days/year x years) >
      or = 2400 hours was considered as 'exposed.' HER-2/neu overexpression was
      evaluated on archival tissue using the DAKO Hercep test, and CD117 testing was
      performed using immunohistochemistry (A4052 polyclonal antibody). RESULTS: 193
      ESSCLC patients were identified. Pesticide exposure data could be obtained on 174
      patients (84 females and 109 males) with a mean age of 68.5 years. 53/174 (30.4%)
      revealed HER-2/neu overexpression. 54/174 (31.03%) specimens showed CD117
      overexpression by IHC. On multivariate analysis, HER-2/neu overexpression was
      associated with diminished survival (p < 0.001). In comparison, CD117 expression
      did not have an adverse prognostic value (p = 0.025). 41/53 (77.4%) patients with
      HER-2/neu overexpression and 47/121 (38.8%) patients without overexpression had
      exposure to pesticides (odds ratio: 5.38; p < 0.01). Among the cohort tested for
      CD117, 29/54 (53.7%) patients with CD117 overexpression and 59/120 (49.2%)
      patients without CD117 overexpression had pesticide exposure (odds ratio: 1.18; p
      = 0.12). CONCLUSION: Pesticide exposure affects HER-2/neu but not CD117
      overexpression. Future studies are needed to determine specific
      pesticide(s)/pesticide components that are responsible for HER-2/neu
      overexpression in ESSCLC, and to validate our findings in other solid tumors that
      overexpress HER-2/neu.

PMID- 15946381
TI  - TGF-beta1 induces human alveolar epithelial to mesenchymal cell transition (EMT).
AB  - BACKGROUND: Fibroblastic foci are characteristic features in lung parenchyma of
      patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of
      mesenchymal cells which underlie sites of unresolved epithelial injury and are
      associated with progression of fibrosis. However, the cellular origins of these
      mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic
      cytokine TGF-beta1 could induce epithelial mesenchymal transition (EMT) in the
      human alveolar epithelial cell line, A549, and investigated the signaling pathway
      of TGF-beta1-mediated EMT. METHODS: A549 cells were examined for evidence of EMT
      after treatment with TGF-beta1. EMT was assessed by: morphology under phase
      contrast microscopy; Western analysis of cell lysates for expression of
      mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression
      of epithelial phenotypic markers including E-cadherin (E-cad). Markers of
      fibrogenesis, including collagens and connective tissue growth factor (CTGF) were
      also evaluated by measuring mRNA level using RT-PCR, and protein by
      immunofluorescence or Western blotting. Signaling pathways for EMT were
      characterized by Western analysis of cell lysates using monoclonal antibodies to
      detect phosphorylated Erk1/2 and Smad2 after TGF-beta1 treatment in the presence
      or absence of MEK inhibitors. The role of Smad2 in TGF-beta1-mediated EMT was
      investigated using siRNA. RESULTS: The data showed that TGF-beta1, but not TNF
      alpha or IL-1beta, induced A549 cells with an alveolar epithelial type II cell
      phenotype to undergo EMT in a time-and concentration-dependent manner. The
      process of EMT was accompanied by morphological alteration and expression of the
      fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a
      downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that
      had undergone EMT showed enhanced expression of markers of fibrogenesis including
      collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-beta1
      induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2
      gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2
      phosphorylation or the observed phenotypic changes. CONCLUSION: Our study shows
      that TGF-beta1 induces A549 alveolar epithelial cells to undergo EMT via Smad2
      activation. Our data support the concept of EMT in lung epithelial cells, and
      suggest the need for further studies to investigate the phenomenon.

PMID- 15946382
TI  - Follow-up care by patient's own general practitioner after contact with out-of
      hours care. A descriptive study.
AB  - BACKGROUND: Little is known about the care process after patients have contacted
      a GP cooperative for out-of-hours care. The objective of this study was to
      determine the proportion of patients who seek follow-up care after contact with a
      GP cooperative for out-of-hours care, and to gain insight into factors that are
      related to this follow-up care. METHODS: A total of 2805 patients who contacted a
      GP cooperative for out-of-hours care were sent a questionnaire. They were asked
      whether they had attended their own GP within a week after their contact with the
      cooperative, and for what reason. To investigate whether other variables are
      related to follow-up care, a logistic regression analysis was applied. Variables
      that entered in this analysis were patient characteristics (age, gender, etc.)
      and patient opinion on correctness of diagnosis, urgency and severity of the
      medical complaint. RESULTS: The response rate was 42%. In total, 48% of the
      patients received follow-up care from their own GP. Only 20% were referred or
      advised to attend their own GP. Others attended because their medical condition
      worsened or because they were concerned about their complaint. Variables that
      predicted follow-up care were the patient's opinion on the correctness of the
      diagnosis, patient's health insurance, and severity of the medical problem.
      CONCLUSION: Almost half of all patients in this study who contacted the GP
      cooperative for out-of-hours care attended their own GP during office hours
      within a week, for the same medical complaint. The most important factor that
      predicted follow-up care from the patient's own GP after an out-of-hours contact
      was the patient's degree of confidence in the diagnosis established at the GP
      cooperative. Despite the limited generalisability, this study is a first step in
      providing insight into the dimension of follow-up care after a patient has
      contacted the GP cooperative for out-of-hours primary care.

PMID- 15946383
TI  - A BAC-based physical map of the Nile tilapia genome.
AB  - BACKGROUND: Cichlid fishes, particularly tilapias, are an important source of
      animal protein in tropical countries around the world. To support selective
      breeding of these species we are constructing genetic and physical maps of the
      tilapia genome. Physical maps linking collections of BAC clones are a critical
      resource for both positional cloning and assembly of whole genome sequences.
      RESULTS: We constructed a genome-wide physical map of the tilapia genome by
      restriction fingerprinting 35,245 bacterial artificial chromosome (BAC) clones
      using high-resolution capillary polyacrylamide gel electrophoresis. The map
      consists of 3,621 contigs and is estimated to span 1.752 Gb in physical length.
      An independent analysis of the marker content of four contigs demonstrates the
      reliability of the assembly. CONCLUSION: This physical map is a powerful tool for
      accelerating genomic studies in cichlid fishes, including comparative mapping
      among fish species, long-range assembly of genomic shotgun sequences, and the
      positional cloning of genes underlying important phenotypic traits. The tilapia
      BAC fingerprint database is freely available at
      http://hcgs.unh.edu/fpc/image.php.

PMID- 15946384
TI  - Inhibition of sarcoplasmic Ca2+-ATPase increases caffeine- and halothane-induced
      contractures in muscle bundles of malignant hyperthermia susceptible and healthy
      individuals.
AB  - BACKGROUND: Malignant hyperthermia (MH) is triggered by halogenated anaesthetics
      and depolarising muscle relaxants, leading to an uncontrolled hypermetabolic
      state of skeletal muscle. An uncontrolled sarcoplasmic Ca2+ release is mediated
      via the ryanodine receptor. A compensatory mechanism of increased sarcoplasmic
      Ca2+-ATPase activity was described in pigs and in transfected cell lines. We
      hypothesized that inhibition of Ca2+ reuptake via the sarcoplasmic Ca2+-ATPase
      (SERCA) enhances halothane- and caffeine-induced muscle contractures in MH
      susceptible more than in non-susceptible skeletal muscle. METHODS: With informed
      consent, surplus muscle bundles of 7 MHS (susceptible), 7 MHE (equivocal) and 16
      MHN (non-susceptible) classified patients were mounted to an isometric force
      transducer, electrically stimulated, preloaded and equilibrated. Following 15 min
      incubation with cyclopiazonic acid (CPA) 25 microM, the European MH standard in
      vitro-contracture test protocol with caffeine (0.5; 1; 1.5; 2; 3; 4 mM) and
      halothane (0.11; 0.22; 0.44; 0.66 mM) was performed. Data as median and
      quartiles; Friedman- and Wilcoxon-test for differences with and without CPA; p <
      0.05. RESULTS: Initial length, weight, maximum twitch height, predrug resting
      tension and predrug twitch height of muscle bundles did not differ between
      groups. CPA increased halothane- and caffeine-induced contractures significantly.
      This increase was more pronounced in MHS and MHE than in MHN muscle bundles.
      CONCLUSION: Inhibition of the SERCA activity by CPA enhances halothane- and
      caffeine-induced contractures especially in MHS and MHE skeletal muscle and may
      help for the diagnostic assignment of MH susceptibility. The status of SERCA
      activity may play a significant but so far unknown role in the genesis of
      malignant hyperthermia.

PMID- 15946385
TI  - A review of the economic burden of ADHD.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common disorder that is
      associated with broad functional impairment among both children and adults. The
      purpose of this paper is to review and summarize available literature on the
      economic costs of ADHD, as well as potential economic benefits of treating this
      condition. A literature search was performed using MEDLINE to identify all
      published articles on the economic implications of ADHD, and authors were
      contacted to locate conference abstracts and articles in press that were not yet
      indexed. In total, 22 relevant items were located including published original
      studies, economic review articles, conference presentations, and reports
      available on the Internet. All costs were updated and presented in terms of year
      2004 US dollars. A growing body of literature, primarily published in the United
      States, has demonstrated that ADHD places a substantial economic burden on
      patients, families, and third-party payers. Results of the medical cost studies
      consistently indicated that children with ADHD had higher annual medical costs
      than either matched controls (difference ranged from 503 dollars to 1,343
      dollars) or non-matched controls (difference ranged from 207 dollars to 1,560
      dollars) without ADHD. Two studies of adult samples found similar results, with
      significantly higher annual medical costs among adults with ADHD (ranging from
      4,929 dollars to 5,651 dollars) than among matched controls (ranging from 1,473
      dollars to 2,771 dollars). A limited number of studies have examined other
      economic implications of ADHD including costs to families; costs of criminality
      among individuals with ADHD; costs related to common psychiatric and medical
      comorbidities of ADHD; indirect costs associated with work loss among adults with
      ADHD; and costs of accidents among individuals with ADHD. Treatment cost
      effectiveness studies have primarily focused on methylphenidate, which is a cost
      effective treatment option with cost-effectiveness ratios ranging from 15,509
      dollars to 27,766 dollars per quality-adjusted life year (QALY) gained. As new
      treatments are introduced it will be important to evaluate their cost
      effectiveness to provide an indication of their potential value to clinicians,
      patients, families, and third-party payers.

PMID- 15946386
TI  - PSA testing for prostate cancer: an online survey of the views and reported
      practice of General Practitioners in the UK.
AB  - BACKGROUND: The role of Prostate Specific Antigen (PSA) testing in the early
      detection of prostate cancer is controversial. Current UK policy stipulates that
      any man who wishes to have a PSA test should have access to the test, provided he
      has been given full information about the benefits and limitations of testing.
      This study aimed to determine UK GPs' current reported practice regarding PSA
      testing, and their views towards informed decision-making and PSA testing.
      METHOD: Online questionnaire survey, with a sample of 421 GPs randomly selected
      from a database of GPs across the UK. RESULTS: 95% (400/421) of GPs responded.
      76% of GPs reported having performed a PSA test for an asymptomatic man at least
      once in the previous three months, with 13% reported having tested more than five
      men in this period. A majority of GPs reported they would do a PSA test for men
      presenting with a family history and requesting a test, for asymptomatic men
      requesting a test and also for men presenting with lower urinary tract symptoms.
      Reported testing rates were highest for men with a family history. Amongst men
      with lower urinary tract symptoms and men with no symptoms, reported testing
      rates were significantly higher for older than younger men. The majority of GPs
      expressed support for the current policy (67%), and favoured both the general
      practitioner and the man being involved in the decision making process (83%). 90%
      of GPs indicated that they would discuss the benefits and limitation of testing
      with the man, with most (61%) preferring to ask the man to make a further
      appointment if he decides to be tested. CONCLUSION: This study indicates that PSA
      testing in asymptomatic men is a regular occurrence in the UK, and that there is
      general support from GPs for the current policy of making PSA tests available to
      'informed' men who are concerned about prostate cancer. While most GPs indicated
      they would discuss the benefits and limitations prior to PSA testing, and most
      GPs favoured a shared approach to decision making, it is not known to what extent
      men are actually being informed. Research is needed to evaluate the most
      effective approach to assisting men in making an informed decision about whether
      or not to have a PSA test.

PMID- 15946387
TI  - Mating-induced reduction in accessory reproductive organ size in the stalk-eyed
      fly Cyrtodiopsis dalmanni.
AB  - BACKGROUND: Internal reproductive organ size is an important determinant of male
      reproductive success. While the response of testis length to variation in the
      intensity of sperm competition is well documented across many taxa, few studies
      address the importance of testis size in determining other components of male
      reproductive success (such as mating frequency) or the significance of size
      variation in accessory reproductive organs. Accessory gland length, but not
      testis length, is both phenotypically and genetically correlated with male mating
      frequency in the stalk-eyed fly Cyrtodiopsis dalmanni. Here we directly
      manipulate male mating status to investigate the effect of copulation on the size
      of both the testes and the accessory glands of C. dalmanni. RESULTS: Accessory
      gland length was positively correlated with male mating frequency. Copulation
      induced a significant decrease in accessory gland size. The size of the accessory
      glands then recovered slowly over the next 8-48 hours. Neither testis length nor
      testis area was altered by copulation. CONCLUSION: These results reveal that the
      time course of accessory gland recovery corresponds to field observations of
      mating behaviour and suggest that accessory gland size may limit male mating
      frequency in C. dalmanni.

PMID- 15946389
TI  - Parasite populations in the brown rat Rattus norvegicus from Doha, Qatar between
      years: the effect of host age, sex and density.
AB  - A total of 179 urban rats were sampled in the city of Doha in Qatar across the
      winter seasons (February-April) of 2002 and 2003. Only two parasites were
      identified, with overall prevalences of 35.8% and 41.3% for the cestode
      Hymenolepis diminuta and the flea Xenopsylla astia respectively. The prevalence
      of H. diminuta was markedly influenced by both year of study and host age, being
      higher in 2003 and amongst older rats. The abundance of infection of H. diminuta
      was influenced by the year of study, host age and sex. Worm burdens in adult rats
      were almost twice as heavy in males compared with females and adults of both
      sexes harboured heavier infections than juveniles. The prevalence of X. astia was
      influenced by both year and host age, being higher in juvenile rats in 2002 and
      in adults in 2003. The abundance of X. astia was significantly higher in 2003 and
      both male and female rats showed similar abundances, but in 2003 females were
      more heavily infested. Reasons for this are discussed in relation to the
      differing foraging strategies shown by male and female rats. The prevalence and
      abundance profiles for both H. diminuta and X. astia were higher overall in 2003
      due to a significant increase in the rat population density, although this did
      not reflect in any increase in parasite species richness. Rats that were infected
      with H. diminuta were almost twice as likely to be infected with X. astia than
      those without the cestode, but when controlled for the effects of year, host age
      and sex, no quantitative interactions were detected between the two parasite
      species.

PMID- 15946388
TI  - The factors associated to psychosocial stress among general practitioners in
      Lithuania. Cross-sectional study.
AB  - BACKGROUND: There are number of studies showing that general practice is one of
      the most stressful workplace among health care workers. Since Baltic States
      regained independence in 1990, the reform of the health care system took place in
      which new role and more responsibilities were allocated to general practitioners'
      in Lithuania. This study aimed to explore the psychosocial stress level among
      Lithuanian general practitioner's and examine the relationship between
      psychosocial stress and work characteristics. METHODS: The cross-sectional study
      of 300 Lithuanian General practitioners. Psychosocial stress was investigated
      with a questionnaire based on the Reeder scale. Job demands were investigated
      with the R. Karasek scale. The analysis included descriptive statistics;
      interrelationship analysis between characteristics and multivariate logistic
      regression to estimate odds ratios for each of the independent variables in the
      model. RESULTS: Response rate 66% (N = 197). Our study highlighted highest
      prevalence of psychosocial stress among widowed, single and female general
      practitioners. Lowest prevalence of psychosocial stress was among males and older
      age general practitioners. Psychosocial stress occurs when job demands are high
      and job decision latitude is low (chi2 = 18,9; p < 0,01). The multivariate
      analysis shows that high job demands (OR 4,128; CI 2,102-8,104; p < 0,001),
      patient load more than 18 patients per day (OR 5,863; CI 1,549-22,188; p < 0,01)
      and young age of GP's (OR 6,874; CI 1,292-36,582; p < 0,05) can be assigned as
      significant predictors for psychosocial stress. CONCLUSION: One half of
      respondents suffering from work related psychosocial stress. High psychological
      workload demands combined with low decision latitude has the greatest impact to
      stress caseness among GP's. High job demands, high patient load and young age of
      GP's can be assigned as significant predictors of psychosocial stress among GP's.

PMID- 15946390
TI  - Hydatidosis in camels (Camelus dromedarius) and their potential role in the
      epidemiology of Echinococcus granulosus in Iran.
AB  - Hydatid cysts were recovered from 35.2% (233/661) of camels (Camelus dromedarius)
      slaughtered in five different regions of Iran. The degree of prevalence between
      males (34.4%) and females (36.6%) was not statistically significant. The highest
      rate of infection (59.3%) was found in the Isfahan region (in the central part of
      Iran) while the lowest (25.7%) was found in Kerman province. The organ
      distribution of cysts was 49.4% in lungs alone, 30.0% in both liver and lungs,
      14.6% in liver only and 6.0% in other organs. Therefore, the lungs were the
      predominant sites of the hydatid cyst. The range in the number of cysts was 1-48
      in infected animals. The majority of the camels had 1-5 cysts, with 21.9%, 11.6%
      and 5.6% of infected camels having 6-10, 11-20 and 21 or more cysts respectively.
      There was a direct relationship between the rate and intensity of infection and
      host age. The fertility rate of lung cysts (69.7%) was higher than that of liver
      cysts (58.7%) and other organs (50.0%) whilst the viability rate of protoscoleces
      of liver fertile cysts (80.3%) was significantly higher than that of lung cysts
      (55.8%) and other organs (57.1%). The role of camels in the epidemiology of
      Echinococcus granulosus in Iran is discussed.

PMID- 15946391
TI  - Taenia spp.: 18S rDNA microsatellites for molecular systematic diagnosis.
AB  - The 18S rDNA gene of adult worms of Taenia parva found in Genetta genetta in the
      Iberian Peninsula and larval stages of T. pisiformis from the wild rabbit
      (Oryctolagus cuniculus) in Tenerife (Canary Islands) were amplified and
      sequenced. The sequences of the 18S rDNA gene of T. parva (1768 bp) and T.
      pisiformis (1760 bp) are reported for the first time (GenBank accession nos.
      AJ555167-AJ555168 and AJ555169-AJ555170, respectively). In 168 alignment
      positions microsatellites in the 18S rDNA of both taxa were detected for the
      first time (TGC in T. parva and TGCT in T. pisiformis) and differences in their
      sequences with different repetition numbers were observed. The use of nucleotide
      sequences of this gene in the resolution of systematic problems in cestodes is
      discussed with reference to the systematic status of Taenia spp. and mainly in
      human taeniids such as T. solium, T. saginata, and Asian human isolates of
      Taenia.

PMID- 15946392
TI  - Helminth parasites of wolves (Canis lupus): a species list and an analysis of
      published prevalence studies in Nearctic and Palaearctic populations.
AB  - A literature survey was undertaken in order to draw up a definitive list of
      helminth parasites of the wolf, Canis lupus. From 27 papers a total of 72
      helminth species from 40 genera were recorded that infect wolves, of which 93%
      were identified from the gastrointestinal tract at necropsy. They comprised 28
      species of nematode, 27 species of cestode, 16 species of trematode and one
      acanthocephalan. Of these, 46 species were able to be included in further meta
      analysis of prevalence data derived from 25 publications for which the total
      number of wolves examined was 1282 (1066 from Nearctic populations, and 216 from
      the Palaearctic region). These two populations were further subdivided into three
      relevent ecosystems or biomes, i.e. temperate/montane (n=216), boreal (n=805) or
      tundra (n=261). The meta-analysis of relative prevalence indicated the most
      common helminth species to be the tapeworm Taenia hydatigena, which occurred at
      relative rates of >30% for either zoogeographic region as well as in each of the
      three biomes. The related tapeworm, Echinococcus granulosus also exhibited high
      meta-prevalence (>19%) in all host biomes. The hookworm Uncinaria stenocephala
      was the most prevalent nematode species by meta-analysis (meta-prevalence 44.9%)
      in the temperate/montane biome, while the ascarid Toxascaris leonina was the
      dominant helminth species (meta-prevalence 73.9%) in the tundra wolf populations.
      Trematodes in the genus Alaria were the dominant fluke (meta-prevalence 3-5%) in
      all biomes. Analysis of published studies for helminth biodiversity using the
      Shannon-Wiener index based on species number and meta-prevalence by region or
      biome, indicated that highest helminth diversity occurred in wolf populations of
      the temperate/ montane biome (Palaearctic), and was lowest in tundra wolf
      populations of the Nearctic (P<0.05). Helminth species assemblage in European
      wolf populations was therefore at least as great or more varied than was recorded
      for the larger less disturbed wolf populations of North America.

PMID- 15946393
TI  - Relationship between bronchopulmonary nematode larvae and relative abundances of
      Spanish ibex (Capra pyrenaica hispanica) from Castilla-La Mancha, Spain.
AB  - The excretion of bronchopulmonary nematode infective larvae was evaluated in 160
      faecal samples of Spanish ibex (Capra pyrenaica hispanica) collected from 13
      populations in Castilla-La Mancha, south-central Spain in September 2003.
      Intensities and prevalences were compared with pasture availability, abundances
      of wild and domestic ungulates at both levels, i.e. for populations and for
      faeces in a two-step procedure. Protostrongylid larvae showed similar infection
      rates (mean intensity: 1.56+/-0.12, n=94; mean prevalence: 25.62+/-6.86%, n=160)
      to Dictyocaulus spp. (mean intensity: 1.03+/-0.11, n=48; mean prevalence: 30.00+/
      7.11%, n=160). At the population level, positive correlations were found between
      the prevalences of both bronchopulmonary taxa. The prevalence in both groups, but
      not intensity, also correlated positively with Spanish ibex abundance indexes
      both for the populations and individual faeces. These findings suggest that: (i)
      parasite spreading across Spanish ibex populations in Castilla-La Mancha could
      respond to host density-dependent processes; and (ii) these populations may have
      similar exposition and/or susceptibility to both bronchopulmonary taxa resulting
      in similar host-parasite patterns, despite their different life cycles.
      Bronchopulmonary outputs in the Spanish ibex from Castilla-La Mancha seems not to
      represent a health risk for this endemic wild ungulate but may be useful in any
      health surveillance scheme for the increasing populations of Spanish ibex.

PMID- 15946394
TI  - Endemic echinostome infections of candidate hosts.
AB  - Wild Lymnaea tomentosa snails, recovered from Lake Wanaka, New Zealand, were
      established in the laboratory. Wild snails, naturally infected with echinostomes,
      provided metacercariae for infection of laboratory maintained snails.
      Metacercarial cysts from wild and laboratory snails were then used to attempt
      infection of definitive host candidates. Laboratory snails provided convenient
      packaging of known numbers of cysts. Metacercariae excysted in the small
      intestines of ducklings to mature in 6 days. Worms were expelled as they became
      gravid. Attempts to establish infections in experimental hosts other than
      ducklings were not successful. No worms were recovered from mice, white rats,
      guinea pigs, hamsters or immunosuppressed white rats.

PMID- 15946395
TI  - The helminth fauna of the barbary partridge Alectoris barbara in Tenerife, Canary
      Islands.
AB  - The helminth fauna of the barbary partridge (Alectoris barbara) in Tenerife
      Island (Canary Archipelago) was studied from 2001 to 2002, as there were no
      records of helminths from this host in the Canary Islands. Seven helminth species
      were identified: two cestodes Choanotaenia infundibulum and Lyruterina
      nigropunctata, and five nematodes Aonchotheca caudinflata, Baruscapillaria
      obsignata, Eucoleus annulatus, Ascaridia galli and Heterakis gallinarum.
      Lyruterina nigropunctata, A. galli and E. annulatus are recorded for first time
      in A. barbara. An analysis of available data on Alectoris spp. reveals the
      importance of intermediate hosts such as arthropods and earthworms in the diet of
      partridges. Terrestrial helminths are dominant species, with monoxenous and
      heteroxenous species being present in similar numbers in different Alectoris
      species along their geographical distribution. Helminth species found in Tenerife
      from A. barbara are poor indicators of the host colonization from North Africa
      because these helminths are species that are commonly found in fowl with a
      cosmopolitan distribution.

PMID- 15946396
TI  - Helminth communities of the barbel Barbus barbus from large river systems in
      Austria.
AB  - The composition and diversity of the total and intestinal component endohelminth
      communities were determined in the cyprinid barbel from three study areas in two
      large river systems in Austria. Two sample sites in the Danube and one site in
      the River Drau are the only free flowing stretches of these rivers in Austria.
      Nine helminth species were identified, with the acanthocephalan Pomphorhynchus
      laevis being dominant in the Danube, with up to 100% prevalence. In the Drau,
      where the dominant species was the cestode Bathybothrium rectangulum, species
      diversity was higher than in the Danube.

PMID- 15946397
TI  - Evaluating the effectiveness of a Mexican strain of Duddingtonia flagrans as a
      biological control agent against gastrointestinal nematodes in goat faeces.
AB  - The use of Duddingtonia flagrans in the control of goat nematodes was
      investigated. Initially, the time of passage of chlamydospores through the
      digestive tract of goats was evaluated. Two groups of seven parasite-free kids
      were formed. Group A received a single dose of 3.5x10(6) D. flagrans
      chlamydospores (FTHO-8 strain) per kg of live weight. Group B did not receive any
      chlamydospores. Faeces were obtained from each kid daily from day 4 prior to
      inoculation until day 5 post-inoculation (PI) and were placed in Petri dishes
      containing water agar. Gastrointestinal nematode infective larvae were added to
      each Petri dish and incubated at 25 degrees C for 7 days. Petri dishes were
      examined to detect the fungus and trapped nematodes. A second trial evaluated the
      effect of D. flagrans on the number of gastrointestinal nematode larvae harvested
      from goat faecal cultures in naturally infected goats. Two groups of seven goats
      were formed. The treated group received a single dose of 3.5x10(6) D. flagrans
      chlamydospores per kg of liveweight. The control group did not receive any
      chlamydospores. Faeces were obtained twice daily from each kid. Two faecal
      cultures were made for each kid. One was incubated for 7 days and the other for
      14 days. Gastrointestinal nematode larvae were recovered from each culture and
      counted. Percentage of larval development reduction was determined using a ratio
      of larvae/eggs deposited in the control and treated groups. Duddingtonia flagrans
      survived the digestive process of goats, and maintained its predatory activity,
      being observed from 21 to 81 h PI (3 to 4 days). A reduction in the infective
      larvae population in the treated group compared to the non-treated group was
      observed in both incubation periods (7 days: 5.3-36.0%; 14 days: 0-52.8%,
      P>0.05). Although a single inoculation of D. flagrans can induce a reduction of
      infective larvae collected from faeces, a different scheme of dosing may be
      needed to enhance the efficacy of D. flagrans in goats.

PMID- 15946398
TI  - Dynamics and predicted decline of Anguillicola crassus infection in European
      eels, Anguilla anguilla, in Neusiedler See, Austria.
AB  - The eel population in Neusiedler See has been maintained by regular massive
      stocking since 1958. After the establishment of the National Park Neusiedler See
      Seewinkel in 1993, eel stocking was prohibited and the population, together with
      the specific parasites of eels, was predicted to decline to extinction within 10
      years. This investigation was undertaken to document the decline and extinction
      of the Anguillicola crassus population in eels. From 1994 to 2001, 720 eels were
      collected from two sites in the lake. Prevalence and abundance of A. crassus were
      lower in spring than in summer and autumn and larger eels harboured more
      parasites than smaller ones. Neither year of study nor sampling site were
      correlated with parasite infection levels. No significant trend in the population
      parameters of A. crassus was detected over the 8 years of the survey. This
      suggested that there had been no significant decline in the eel population. This
      suggestion was confirmed by investigations of the fishery, which also found
      evidence of regular illegal stocking. The stability of the A. crassus population
      over the past decade seems to reflect the lack of change in eel population
      density. No mass mortalities of eels occurred over the period despite the many
      similarities between Neusiedler See and Lake Balaton in Hungary. Differences in
      eel size, eel diet and the lack of large-scale insecticide use are discussed as
      possible explanations for the absence of eel mass mortalities in Neusiedler See.

PMID- 15946399
TI  - The life cycle of Paraquimperia tenerrima: a parasite of the European eel
      Anguilla anguilla.
AB  - Previous studies on the life history of the nematode eel specialist Paraquimperia
      tenerrima (Nematoda: Quimperiidae) have failed to determine whether an
      intermediate host is required in the life cycle. In the laboratory, eggs failed
      to hatch below 10 degrees C, hatching occurring only at temperatures between 11
      and 30 degrees C. Survival of the free-living second stage larvae (L2) was also
      temperature dependent, with maximal survival between 10 and 20 degrees C. Total
      survival of the free-living stages (eggs and L2) is unlikely to exceed a month at
      normal summer water temperatures, confirming that parasite could not survive the
      6 month gap between shedding of eggs in spring and infection of eels in early
      winter outside of a host. Eels could not be infected directly with L2, nor could
      a range of common freshwater invertebrate species. Third stage larvae (L3)
      resembling P. tenerrima were found frequently and abundantly in the swimbladder
      of minnows Phoxinus phoxinus from several localities throughout the year and were
      able to survive in this host in the laboratory for at least 6 months. Third stage
      larvae identical to these larvae were recovered from minnows experimentally fed
      L2 of P. tenerrima, and eels infected experimentally with naturally and
      experimentally infected minnows were found to harbour fourth stage larvae (L4)
      and juvenile P. tenerrima in their intestines. Finally, the whole life cycle from
      eggs to adult was completed in the laboratory, confirming that minnows are an
      obligate intermediate host for P. tenerrima.

PMID- 15946400
TI  - Cercarial tail loss in Echinostoma caproni: the influence of in vivo encystment
      and copper sulphate.
AB  - Echinostoma caproni tail loss was studied in vitro in the presence of the
      toxicant copper sulphate (CuSO4) in concentrations ranging from 1 to 10 000 mg l(
      1) in standardized artificial spring water (pH 7.4, osmolarity 34 mOsm kg(-1)
      H2O, Ca(2+) 20 mg l(-1)) at 23 degrees C. Tail loss was also studied in the
      absence of toxicants during in vivo encystment of the cercariae in juvenile
      Biomphalaria glabrata. As the concentration of CuSO4 increased, the percentage of
      cercarial tail loss increased. By 2 h in 10 000 mg l(-1), 1000 mg l(-1) and 100
      mg l(-1) CuSO4, 50%, 23% and 13%, respectively, of the cercariae had lost their
      tails. In the in vivo studies, by 1 h PI, 59+/-5% of cercariae had lost their
      tails and only 4+/-1% of the cercariae were actively swimming in the multi-well
      dishes. At 3 h PI, 72+/-3% of the cercariae began to form cysts within the
      snails.

PMID- 15946401
TI  - Obesity in Parkinson's disease patients on electrotherapy: collateral damage,
      adiposity rebound or secular trends?

PMID- 15946402
TI  - The contribution of plant-derived proteinases to the breakdown of fresh pasture
      protein in the rumen.

PMID- 15946403
TI  - Defining best practice for microarray analyses in nutrigenomic studies.
AB  - Microarrays represent a powerful tool for studies of diet-gene interactions.
      Their use is, however, associated with a number of technical challenges and
      potential pitfalls. The cost of microarrays continues to drop but is still
      comparatively high. This, coupled with the complex logistical issues associated
      with performing nutritional microarray studies, often means that compromises have
      to be made in the number and type of samples analysed. Additionally, technical
      variations between array platforms and analytical procedures will almost
      inevitably lead to differences in the transcriptional responses observed.
      Consequently, conflicting data may be produced, important effects may be missed
      and/or false leads generated (e.g. apparent patterns of differential gene
      regulation that ultimately prove to be incorrect or not significant). This is
      likely to be particularly true in the field of nutrition, in which we expect that
      many dietary bioactive agents at nutritionally relevant concentrations will
      elicit subtle changes in gene transcription that may be critically important in
      biological terms but will be difficult to detect reliably. Thus, great care
      should always be taken in designing and executing microarray studies. This
      article seeks to provide an overview of both the main practical and theoretical
      considerations in microarray use that represent potential sources of technical
      variation and error. Wherever possible, recommendations are made on what we
      propose to be the best approach. The overall aims are to provide a basic
      framework of advice for researchers who are new to the use of microarrays and to
      promote a discussion of standardisation and best practice in the field.

PMID- 15946404
TI  - Alpha-linolenic acid but not conjugated linolenic acid is hypocholesterolaemic in
      hamsters.
AB  - Conjugated linolenic acid (CLN) refers to a group of octadecatrienoic acid
      isomers that have three double bonds in conjugation. Both pomegranate and tung
      seed oils are rich in CLN but the major isomer in the former is
      cis9,trans11,cis13 while in the latter it is cis9,trans11,trans13. The present
      study examined the effects of CLN, isolated from either pomegranate seed oil or
      tung seed oil, and alpha-linolenic acid (LN), isolated from flaxseed oil, on
      serum cholesterol levels in male hamsters (body weight 105 g; age 10 weeks) fed a
      0.1% cholesterol and 10% lard diet, for a period of 6 weeks. All hamsters were
      allowed free access to food and fluid. The blood samples were taken by bleeding
      from the retro-orbital sinus into a heparinized capillary tube under light ether
      anaesthesia after overnight fasting at weeks 0, 2, 4 and 6. It was found that
      supplementation of CLN at levels of 12.2-12.7 g/kg diet exhibited no significant
      effect on serum cholesterol level while LN at a similar level of supplementation
      had serum cholesterol reduced by 17-21% compared with the control diet containing
      no LN and CLN. Supplementation of CLN and LN significantly decreased hepatic
      cholesterol but no effect was observed on heart and kidney cholesterol levels. It
      was concluded that LN possessed hypocholesterolaemic activity while CLN had no
      effect on blood cholesterol, at least in hamsters.

PMID- 15946405
TI  - Dietary whey protein increases liver and skeletal muscle glycogen levels in
      exercise-trained rats.
AB  - We investigated the effect of different types of dietary protein on glycogen
      content in liver and skeletal muscle of exercise-trained rats. Twenty-four male
      Sprague-Dawley rats (approximately 100 g; n 6 per group) were divided into
      sedentary or exercise-trained groups with each group being fed either casein or
      whey protein as the source of dietary protein. Rats in the exercised groups were
      trained during 2 weeks using swimming exercise for 120 min/d, 6 d/week. Exercise
      training resulted in an increase in the skeletal muscle glycogen content.
      Furthermore, the whey protein group significantly increased the skeletal muscle
      glycogen content compared with the casein group. The increase in glycogen content
      in liver was significantly greater in rats fed the whey protein diet compared
      with those fed the casein diet. We also found that the whey protein diet
      increased the activity of liver glucokinase, whereas it decreased the activities
      of 6-phosphofructokinase and pyruvate kinase compared with the casein diet.
      However, hepatic total glycogen synthase activity and mRNA expression were
      similar with the two diets. In the skeletal muscle, whey protein decreased only 6
      phosphofructokinase activity compared with casein. Total glycogen synthase
      activity in the skeletal muscle in the whey protein group was significantly
      higher than that in the casein group. The present study is the first to
      demonstrate that a diet based on whey protein may increase glycogen content in
      liver and skeletal muscle of exercise-trained rats. We also observed that whey
      protein regulated glycogen metabolism in these two tissues by different
      mechanisms.

PMID- 15946406
TI  - Catabolism through the threonine dehydrogenase pathway does not account for the
      high first-pass extraction rate of dietary threonine by the portal drained
      viscera in pigs.
AB  - In pigs the extensive threonine utilization by the splanchnic tissues explains
      the relative inefficiency of dietary threonine conversion for body protein
      accretion. Two experiments were conducted to estimate the contribution of the
      portal drained viscera (PDV) and the liver to threonine metabolism and especially
      catabolism in growing pigs. In the first experiment, four pigs were surgically
      prepared for chronic catheter insertion in the portal, hepatic and jugular veins
      and in the carotid artery. They were continuously infused with L-[1
      (13)C]threonine through the jugular catheter. The PDV and total splanchnic
      viscera (PDV and the liver) extracted 14.3 and 18.8% of arterial threonine input,
      respectively. In a second experiment, we studied the metabolism of dietary
      threonine in the PDV and the liver in six female growing pigs. Animals were
      surgically prepared as in the first experiment except that L-[1-(13)C]threonine
      and [(15)N]glycine were continuously infused in the duodenum for 10 h. Unlabelled
      and labelled threonine and glycine PDV, liver and splanchnic tissues balance were
      calculated from plasma samples taken during the last 2 h of this infusion.
      Splanchnic tissues extracted 60% of infused labelled threonine, 88% of which was
      extracted by PDV so that threonine extraction by the liver was low. Both the
      liver and the pancreas can degrade threonine through the L-threonine 3
      dehydrogenase pathway but not the intestine. Our data suggest that threonine
      catabolism through the L-threonine 3-dehydrogenase pathway was only a minor
      component of total threonine utilization in the splanchnic tissues.

PMID- 15946407
TI  - Increasing ursodeoxycholic acid in the enterohepatic circulation of pigs through
      the administration of living bacteria.
AB  - We investigated the feasibility of increasing ursodeoxycholic acid (UDCA) in the
      enterohepatic circulation of pigs by administering living bacteria capable of
      epimerising endogenous amidated chenodeoxycholic acid (CDCA) to UDCA. We first
      demonstrated that combining Bifidobacterium animalis DN-173 010, as a bile salt
      hydrolysing bacterium, and Clostridium absonum ATCC 27555, as a CDCA to UDCA
      epimerising bacterium, led to the efficient epimerisation of glyco- and tauro
      CDCA in vitro, with respective UDCA yields of 55.8 (SE 2.8) and 36.6 (SE 1.5)%.
      This strain combination was then administered to hypercholesterolaemic pigs over
      a 3-week period, as two daily preprandial doses of either viable (six
      experimental pigs) or heat-inactivated bacteria (six controls). The main effects
      of treatment were on unconjugated bile acids (P=0.035) and UDCA (P<0.0001)
      absorbed into the portal vein, which increased 1.6-1.7- and 3.5-7.5-fold,
      respectively, under administration of living compared with inactivated bacteria.
      In bile, UDCA did not increase significantly, but the increase in biliary
      lithocholic acid with time in the controls was not observed in the experimental
      pigs (P=0.007), and the same trend was observed in faeces. All other variables
      (biliary lipid equilibrium, plasma lipid levels and partition of cholesterol
      between the different lipoprotein classes) remained unaffected by treatment
      throughout the duration of the experiment. In conclusion, it is feasible to
      increase the bioavailability of UDCA to the intestine and the liver by
      administering active bacteria. This may represent an interesting new probiotic
      activity, provided that in future it could be expressed by a safe food micro
      organism.

PMID- 15946408
TI  - Prenatal exposure to maternal undernutrition induces adult cardiac dysfunction.
AB  - An adverse environmental experience of the growing fetus may lead to permanent
      changes in the structure and function of organs that may predispose the
      individual to chronic diseases in later life; however, nothing is known about the
      occurrence and mechanisms of heart failure. We employed a rat model in which
      pregnant dams were fed diets containing either 180 g (normal) or 90 g (low)
      casein/kg for 2 weeks before mating and throughout pregnancy. The ejection
      fraction (EF) of the pups exposed to the low-protein (LP) diet was severely
      depressed in the first 2 weeks of life and was associated with an increase in
      cardiomyocyte apoptosis. This early depressed cardiac function was followed by
      progressive recovery and normalization of the EF of the offspring in the LP
      group. The left ventricular (LV) internal diameters were increased between 24 h
      and 84 d (12 weeks) of age in the LP-exposed group. Although between 3 d and 2
      weeks of age the LV wall of the heart in the LP group was thinner, a progressive
      increase in LV wall thickness was seen. At 40 weeks of age, although the EF was
      normal, a two-fold elevation in LV end-diastolic pressure, reduced cardiac
      output, decreased maximum rates of contraction and relaxation, and reduced mean
      arterial pressure were observed. Our findings demonstrate that exposure of the
      developing fetus to a maternal LP diet programs cardiac dysfunction in the
      offspring in later life.

PMID- 15946409
TI  - Influence of disodium malate on microbial growth and fermentation in rumen
      simulation technique fermenters receiving medium- and high-concentrate diets.
AB  - Two incubation trials were carried out with the rumen-simulation technique
      (RUSITEC). In each trial, four vessels received a diet of grass hay and
      concentrate (600 and 400 g/kg DM, respectively; diet F), and the other four were
      fed a diet composed of concentrate and barley straw (900 and 100 g/kg DM,
      respectively; Diet C). Vessels were given 20 g of the corresponding diet daily,
      and half of them were supplemented with disodium malate to achieve a final
      concentration of 6.55 mM. There were no effects (P>0.05) of malate either on pH
      or on the daily production of NH3-N, but malate treatment increased (P<0.05) DM,
      neutral detergent and acid detergent fibre disappearance after 48 h incubation.
      The daily production of propionate and butyrate increased (P<0.001), and the
      ratio CH4:volatile fatty acids decreased (P<0.001) by supplementing both diets
      with malate. Whereas adding malate to the F diet produced an increase in acetate
      production (P=0.011) and the growth of solid-associated micro-organisms
      (P=0.037), no effects (P>0.05) were observed for diet C. For both diets, there
      were no differences (P>0.05) between treatments in the daily flow of liquid
      associated micro-organisms measured using (15)N as a microbial marker. These
      results indicate that malate stimulated the in vitro fermentation of both diets
      by increasing the apparent disappearance of the diet and decreasing the ratio of
      CH4:volatile fatty acids, but a greater response was observed with diet F. If
      these results are confirmed in vivo, malate could be used as a feed additive for
      ruminants fed diets containing medium proportions of forage (i.e. dairy animals)
      and not only in animals fed high-concentrate diets, as has so far been proposed.

PMID- 15946410
TI  - High rates of exogenous carbohydrate oxidation from a mixture of glucose and
      fructose ingested during prolonged cycling exercise.
AB  - A recent study from our laboratory has shown that a mixture of glucose and
      fructose ingested at a rate of 1.8 g/min leads to peak oxidation rates of
      approximately 1.3 g/min and results in approximately 55% higher exogenous
      carbohydrate (CHO) oxidation rates compared with the ingestion of an isocaloric
      amount of glucose. The aim of the present study was to investigate whether a
      mixture of glucose and fructose when ingested at a high rate (2.4 g/min) would
      lead to even higher exogenous CHO oxidation rates (>1.3 g/min). Eight trained
      male cyclists (VO2max: 68+/-1 ml/kg per min) cycled on three different occasions
      for 150 min at 50% of maximal power output (60+/-1% VO2max) and consumed either
      water (WAT) or a CHO solution providing 1.2 g/min glucose (GLU) or 1.2 g/min
      glucose+1.2 g/min fructose (GLU+FRUC). Peak exogenous CHO oxidation rates were
      higher (P<0.01) in the GLU+FRUC trial compared with the GLU trial (1.75 (SE 0.11)
      and 1.06 (SE 0.05) g/min, respectively). Furthermore, exogenous CHO oxidation
      rates during the last 90 min of exercise were approximately 50% higher (P<0.05)
      in GLU+FRUC compared with GLU (1.49 (SE 0.08) and 0.99 (SE 0.06) g/min,
      respectively). The results demonstrate that when a mixture of glucose and
      fructose is ingested at high rates (2.4 g/min) during 150 min of cycling
      exercise, exogenous CHO oxidation rates reach peak values of approximately 1.75
      g/min.

PMID- 15946411
TI  - Secondary infection of Nippostrongylus brasiliensis in lactating rats is
      sensitive to dietary protein content.
AB  - Lactating mammals usually exhibit a breakdown of immunity to parasites, i.e. they
      have larger worm burdens than their non-lactating counterparts. Here, we tested
      the hypothesis that a secondary infection with Nippostrongylus brasiliensis in
      lactating rats is sensitive to dietary protein content. We also tested whether
      this infection affects host food intake. Rats either remained uninfected
      throughout the study or were given a single infection before mating (primary
      infection) and re-infected on day 2 of lactation (secondary infection) with 1600
      infective larvae. Infected rats were fed foods during lactation formulated to
      supply 100 (low protein; LP), 200 (medium protein; MP) or 300 (high protein; HP)
      g crude protein per kg DM; non-infected rats were fed either the LP or HP food.
      Litter size was standardized to ten pups between parturition (day 0) and
      secondary infection (day 2). Ten days after secondary infection, MP and HP rats
      had excreted fewer nematode eggs, and had fewer adult nematodes in their small
      intestine and nematode eggs in their colon than the LP rats. Primary infection
      increased food intake in late pregnancy, and increased maternal body weight and
      litter size at parturition. Secondary infection did not affect mean food intake,
      maternal and litter weight, although food intake was reduced for 1 d following
      infection. These results support the view that a secondary infection with N.
      brasiliensis is sensitive to dietary protein content, and that the latter
      infection does not impair lactational performance. Future studies may focus on
      elucidating the nutritional sensitivity of immune responses underlying the
      reduced secondary N. brasiliensis infection.

PMID- 15946412
TI  - Vitamin C status and collagen cross-link ratios in Gambian children.
AB  - Vitamin C (ascorbate) is essential for hydroxylation of prolyl and lysyl residues
      in nascent collagen, the failure of which leads to connective tissue lesions of
      scurvy. Of the pyridinium-type cross-links in mature collagen, pyridinoline
      requires more hydroxylysyl residues than does deoxypyridinoline. Our study tested
      the hypothesis that pyridinoline:deoxypyridinoline ratios in urinary degradation
      products may vary with ascorbate status in man. These ratios were compared
      between British and Gambian prepubertal boys, mean age 8.3 years, and in Gambian
      boys between two seasons with contrasting ascorbate availability. The mean cross
      links ratio in 216 British boys was 4.36 (SD 0.71), significantly greater
      (P<0.0001) than in sixty-two Gambian boys: 3.83 (SD 0.52). In the Gambians the
      cross-links ratio was significantly higher in the dry season (with high ascorbate
      intake and status) than in the rains (with low intake and status). A 7-week
      controlled intervention was carried out in Gambian boys during the rainy season
      (the 'hungry' season, when vitamin C-containing foods are virtually unavailable):
      100 mg ascorbate/d was given to one group of thirty-two Gambian boys and placebo
      to another group. The intervention did not, however, significantly alter the
      cross-link ratio, possibly because the response time and/or intervention-response
      delay is >7 weeks. If confirmed, the putative association between ascorbate and
      collagen cross-link ratios in man could become the basis for a functional test
      for adequacy of ascorbate status.

PMID- 15946413
TI  - Early enteral feeding compared with parenteral nutrition after oesophageal or
      oesophagogastric resection and reconstruction.
AB  - After resective and reconstructive surgery in the gastrointestinal tract, oral
      feeding is traditionally avoided in order to minimize strain to the anastomoses
      and to reduce the inherent risks of the postoperatively impaired gastrointestinal
      motility. However, studies have given evidence that the small bowel recovers its
      ability to absorb nutrients almost immediately following surgery, even in the
      absence of peristalsis, and that early enteral feeding would preserve both the
      integrity of gut mucosa and its immunological function. The aim of this study was
      to investigate the impact of early enteral feeding on the postoperative course
      following oesophagectomy or oesophagogastrectomy, and reconstruction. Between May
      1999 and November 2002, forty-four consecutive patients (thirty-eight males and
      six females; mean age 62, range 30-82) with oesophageal carcinoma (stages I-III),
      who had undergone radical resection and reconstruction, entered this study (early
      enteral feeding group; EEF). A historical group of forty-four patients (thirty
      seven males and seven females; mean age 64, range 41-79; stages I-III) resected
      between January 1997 and March 1999 served as control (parenteral feeding group;
      PF). The duration of both postoperative stay in the Intensive Care Unit (ICU) and
      the total hospital stay, perioperative complications and the overall mortality
      were compared. Early enteral feeding was administered over the jejunal line of a
      Dobhoff tube. It started 6 h postoperatively at a rate of 10 ml/h for 6 h with
      stepwise increase until total enteral nutrition was achieved on day 6. In the
      controls oral enteral feeding was begun on day 7. If compared to the PF group,
      EEF patients recovered faster considering the duration of both stay in the ICU
      and in the hospital. There was a significant difference in the interval until the
      first bowel movements. No difference in overall 30 d mortality was identified. A
      poor nutritional status was a significant prognostic factor for an increased
      mortality. Early enteral feeding significantly reduces the duration of ICU
      treatment and total hospital stay in patients who undergo oesophagectomy or
      oesophagogastrectomy for oesophageal carcinoma. The mortality rate is not
      affected.

PMID- 15946414
TI  - Response of circulating leptin to Ramadan daytime fasting: a circadian study.
AB  - Although the effects of short-term fasting on serum leptin concentrations are
      known, those resulting from long-lasting modifications of food intake schedule,
      as during the month of Ramadan, have not yet been extensively studied. Therefore,
      serum concentrations of leptin were measured around the clock at 4-hourly
      intervals before the beginning of Ramadan and on the twenty-third day of Ramadan
      daytime fasting in ten male subjects keeping the same usual activity pattern and
      general synchronisation in both situations. Time series were analysed with
      repeated measures ANOVA and Cosinor. No significant changes in amplitude or 24 h
      mean concentration were seen, but significant shifts of 5 h 30 min in peak and
      trough serum leptin levels were found on the twenty-third day of Ramadan.

PMID- 15946415
TI  - Evaluation of three dietary assessment methods and serum biomarkers as measures
      of fruit and vegetable intake, using the method of triads.
AB  - The validity of fruit and vegetable intake estimated by 14 d weighed records, a
      twenty-seven-item food frequency questionnaire (FFQ) and a 180-item FFQ was
      investigated using serum carotenoids as the validity criterion. In addition, the
      method of triads was used to assess the validity of fruit and vegetable intake
      estimated from the FFQ and serum carotenoids. One hundred Norwegian men completed
      14 d weighed records and the 180-item FFQ. Eighty-six of them also completed the
      twenty-seven item FFQ. The partial correlation coefficients between serum
      carotenoids and fruit and vegetable intake were slightly higher for the 14 d
      weighed records than for the two FFQ, but no difference was observed between the
      180- and the twenty-seven item FFQ. The strongest correlations were observed
      between vegetable intake and serum alpha-carotene. The highest validity
      coefficients (VC) were observed for vegetable intake estimated from weighed
      records, the 180-item FFQ, the twenty-seven item FFQ and by the biomarker serum
      alpha-carotene, with VC of 0.77, 0.58, 0.51 and 0.67, respectively. In
      conclusion, the short FFQ gave as valid estimates for fruit and vegetable intake
      as the long FFQ. Both the estimated partial correlation coefficients and VC
      suggest that serum alpha-carotene is the best biomarker for intake of vegetable
      alone and total intake of fruit and vegetables in this population of Norwegian
      men, but the biomarkers did not perform any better than the FFQ.

PMID- 15946416
TI  - Association of fatty acids in serum phospholipids with hay fever, specific and
      total immunoglobulin E.
AB  - The dietary intake of certain fatty acids might contribute to the development of
      allergic diseases such as hay fever and asthma. We investigated the association
      between the concentrations of fifteen fatty acids in serum phospholipids, as a
      marker of dietary intake and metabolism, and hay fever, allergic sensitisation
      and total IgE in adults. Data from a population-based cross-sectional study on
      respiratory health, including the measurement of fatty acids in the serum
      phospholipids of 740 adults between 20 and 64 years of age, were analysed.
      Positive associations were found between hay fever and arachidonic acid, and
      allergic sensitisation and oleic acid. No other fatty acids showed any
      association with hay fever or allergic sensitisation. Elevated levels of total
      IgE were not related to fatty acids. Concentrations of long-chain n-3 fatty
      acids, trans fatty acids or saturated fatty acids in serum phospholipids were not
      associated with allergic diseases in adults in this study. The present result on
      the association between hay fever and arachidonic acid is consistent with current
      hypotheses but warrants further research.

PMID- 15946417
TI  - The National School Fruit Scheme produces short-term but not longer-term
      increases in fruit consumption in primary school children.
AB  - The National School Fruit Scheme (NSFS) provides one free piece of fruit each
      school day to children, aged 4 to 6 years, attending state schools in England.
      The aims of the present study were to determine if NSFS was associated with a
      higher fruit consumption in infant school children (4-6 years old), and to assess
      whether fruit consumption was higher in junior school children (7-8 years old)
      who had received free fruit as infants compared with those who had not. The
      present cross-sectional study involved seventeen schools, eight in the NSFS
      (study schools) and nine not in the NSFS (control schools). Study and control
      schools were selected in areas of similar levels of deprivation. All schools were
      on the outskirts of London in Southeast England. A retrospective 24 h food tick
      list was given to each pupil in Reception to Year 4 to take home for their
      parents to complete and return. Response rate was 51%. Median total fruit
      consumption (excluding fruit juice) in infants receiving free fruit was 117 g/d
      compared with 67 g/d in infants not receiving free fruit (P<0.001). Median
      consumption in juniors who had received free fruit at school as infants did not
      differ from those who had not (83 g/d v. 86 g/d). The NSFS has increased fruit
      consumption in infant school children. It does not appear to have longer-term
      effects in junior school children. If the scheme is to affect dietary habits and
      improve health in the long term, further interventions will be needed.

PMID- 15946418
TI  - Effect of tea catechins on postprandial plasma lipid responses in human subjects.
AB  - Epidemiological surveys suggest that a higher intake of tea may be associated
      with a lower risk of CHD. There is accumulating evidence that postprandial
      lipaemia makes a substantial contribution to the incidence of CHD. Our aim was,
      therefore, to evaluate the effect of tea catechins (major ingredients in green
      tea) on postprandial lipid responses in human subjects after the consumption of
      test meals. In a randomized triple-crossover design, nine male subjects with mild
      or borderline hypertriacylglycerolaemia consumed 10 (control), 224 (moderate
      dose) and 674 mg (high dose) of the assigned tea catechins three times each along
      with a standardized light meal consisting of a piece of bread spread with 20 g
      butter. Plasma lipids were measured in the fasting state and 1, 2, 3, 4 and 6 h
      after consuming the light meal. Results showed that, compared with the control,
      moderate and high doses of tea catechins reduced the incremental area under the
      plasma triacylglycerol curves by 15.1 and 28.7%, respectively. Next, the rapid
      elevation of remnant-like particle cholesterol was significantly inhibited by a
      high dose of tea catechins 2 h after consuming the light meal (P<0.01). In the
      range of tea catechin dosages, no significant differences were observed in the
      postprandial responses for plasma total cholesterol or NEFA at any time point. In
      conclusion, this trial demonstrated that tea catechins attenuated the
      postprandial increase in plasma triacylglycerol levels following a fat load.
      These results may provide evidence for one of the possible mechanisms involved in
      lowering the incidence of CVD, and may prove useful in further studies on the
      beneficial health effects of tea drinking.

PMID- 15946419
TI  - The effect of dietary vitamin E and fatty acid supplementation of pregnant and
      lactating ewes on placental and mammary transfer of vitamin E to the lamb.
AB  - The present study investigated the effect of maternal vitamin E and fatty acid
      supplementation on lamb antioxidant status. Forty-eight ewes were fed one of four
      concentrate diets supplemented with a basal (50 mg/kg) or supranutritional (500
      mg/kg) level of vitamin E plus a source of either saturated fat (Megalac; Volac
      Ltd, Royston, Hertfordshire, UK) or long-chain PUFA (fish oil) from 6 weeks
      prepartum until 4 weeks postpartum. Blood samples were taken from ewes and lambs
      at intervals throughout the experiment and, at parturition, muscle, brain and
      blood samples were obtained from twelve lambs (three per treatment). Colostrum
      and milk samples were obtained at 12 h and 21 d after parturition, respectively.
      Supranutritional vitamin E supplementation of the ewe significantly increased
      concentrations of vitamin E in neonatal lamb tissues although plasma
      concentrations were undetectable. A significant increase in lamb birth weight
      resulted from increasing the dietary vitamin E supply to the ewe. Furthermore,
      maternal plasma, colostrum and milk vitamin E concentrations were increased by
      vitamin E supplementation, as were lamb plasma concentrations at 14 d of age.
      Neonatal vitamin E status was not significantly affected by fat source although
      plasma vitamin E concentrations in both ewes and suckling lambs were reduced by
      fish oil supplementation of the ewe. Fish oil supplementation reduced vitamin E
      concentrations in colostrum and milk and the activity of glutathione peroxidase
      in suckling lambs. The data suggest that the vitamin E status of the neonatal and
      suckling lamb may be manipulated by vitamin E supplementation of the ewe during
      pregnancy and lactation.

PMID- 15946420
TI  - Dietary isohumulones, the bitter components of beer, raise plasma HDL-cholesterol
      levels and reduce liver cholesterol and triacylglycerol contents similar to
      PPARalpha activations in C57BL/6 mice.
AB  - The effects of dietary isohumulones, the main components accounting for the
      bitter taste of beer, on lipid metabolism were examined. Young female C57BL/6N
      mice were fed diets containing isomerized hop extract (IHE), which consists
      mainly of isohumulones. Administration of IHE with an atherogenic (high-fat and
      high-cholesterol) diet for 2 weeks resulted in a significant increase in plasma
      HDL-cholesterol (P<0.01), along with a concomitant reduction in the
      atherosclerosis index, an increase in liver weight and a decrease in body weight
      gain in a dose-dependent manner. When animals received IHE with either a
      cholesterol or a basal diet for 1 week, significant decreases in the liver
      content of cholesterol (P<0.01) and triacylglycerol (cholesterol diet, P<0.01)
      were observed. Quantitative analyses of hepatic mRNA levels revealed that IHE
      administration resulted in up-regulation of mRNA for acyl-CoA oxidase, acyl-CoA
      synthetase, hydroxymethylglutaryl-CoA synthetase, lipoprotein lipase and fatty
      acid transport protein, and down-regulation of mRNA for Apo CIII and Apo AI.
      Administration of purified isohumulones effectively resulted in the same changes
      as IHE. Administration of fenofibrate, an agonist for PPARalpha, with a
      cholesterol diet caused marked hepatomegaly, an increase in plasma HDL
      cholesterol, a decrease in hepatic cholesterol content, and alterations in
      hepatic mRNA levels similar to those observed in mice given IHE. Taken together,
      these results suggest that the modulation of lipid metabolism observed in mice
      fed diets containing isohumulones is, at least in part, mediated by activation of
      PPARalpha.

PMID- 15946421
TI  - Dieting. Makes you fat?

PMID- 15946422
TI  - The mechanisms of surgical treatment of type 2 diabetes.

PMID- 15946423
TI  - Changes in insulin resistance following bariatric surgery: role of caloric
      restriction and weight loss.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western
      world is steadily increasing. Bariatric surgery is an effective treatment of T2DM
      in obese patients. The mechanism by which weight loss surgery improves glucose
      metabolism and insulin resistance remains controversial. In this review, we
      propose that two mechanisms participate in the improvement of glucose metabolism
      and insulin resistance observed following weight loss and bariatric surgery:
      caloric restriction and weight loss. Nutrients modulate insulin secretion through
      the entero-insular axis. Fat mass participates in glucose metabolism through the
      release of adipocytokines. T2DM improves after restrictive and bypass procedures,
      and combinations of restrictive and bypass procedures in morbidly obese patients.
      Restrictive procedures decrease caloric and nutrient intake, decreasing the
      stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also
      affect the entero-insular axis by diverting nutrients away from the proximal GI
      tract and delivering incompletely digested nutrients to the distal GI tract. GBP
      and biliopancreatic diversion combine both restrictive and bypass mechanisms. All
      procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass
      significantly affects circulating levels of adipocytokines, which favorably
      impact insulin resistance. The data reviewed here suggest that all forms of
      weight loss surgery lead to caloric restriction, weight loss, decrease in fat
      mass and improvement in T2DM. This suggests that improvements in glucose
      metabolism and insulin resistance following bariatric surgery result in the short
      term from decreased stimulation of the entero-insular axis by decreased caloric
      intake and in the long-term by decreased fat mass and resulting changes in
      release of adipocytokines. Observed changes in glucose metabolism and insulin
      resistance following bariatric surgery do not require the posit of novel
      regulatory mechanisms.

PMID- 15946424
TI  - Loss of insulin resistance after Roux-en-Y gastric bypass surgery: a time course
      study.
AB  - BACKGROUND: Gastric bypass has repeatedly been shown to improve and even cure
      type 2 diabetes by substantially improving insulin resistance. The mechanism by
      which it achieves this is not currently known, but some have hypothesized that
      there may be important humoral effects brought about by the bypass of the
      stomach, duodenum or proximal jejunum. A better understanding of the time course
      of the changes in insulin resistance after surgery might assist our understanding
      of potential mechanisms. METHODS: Intravenous glucose tolerance tests (IVGTT)
      were performed in 26 severely obese patients on the morning of gastric bypass
      surgery and again 6 days later. In addition insulin resistance was assessed in 71
      patients undergoing gastric bypass surgery by the homeostasis model assessment
      (HOMA) method before surgery, and again at 6 days, 3, 6, 9, and 12 months.
      Patients were divided into 3 groups for analysis: diabetics, impaired glucose
      tolerance and normal glucose tolerance. RESULTS: All 3 groups of patients were
      noted to have insulin resistance prior to surgery. This was greatest in the
      diabetic patients, as indicated by HOMA. There was marked loss of/improvement in
      insulin resistance within 6 days of gastric bypass by both IVGTT and HOMA methods
      in all groups, which was maintained over the 12-month period. The study included
      31 diabetic patients, of whom only 3 required medication following hospital
      discharge. CONCLUSION: The changes in insulin resistance seen after gastric
      bypass, which are responsible for the resolution or improvement of type 2
      diabetes occur within 6 days of the surgery, before any appreciable weight loss
      has occurred. This finding has implications for our understanding of the
      mechanism of insulin resistance in severely obese patients and is consistent with
      a humoral mechanism emanating from the GI tract.

PMID- 15946425
TI  - Operative experience and follow-up in a cohort of patients with a BMI > or =70
      kg/m2.
AB  - BACKGROUND: Roux-en-Y gastric bypass (RYGBP) has been found to be a safe and
      effective operation for the morbidly obese whether performed open or
      laparoscopically. Weight loss has been substantial and sustained. Less is known
      about those at the extremes of obesity, with BMI > or =70 kg/m2 with regard to
      safety and efficacy. This study is a retrospective review of a cohort of such
      patients, to examine operative experience and response to surgical treatment.
      METHODS: A cohort of 34 patients who underwent open RYGBP at one institution was
      retrospectively reviewed. All operations were performed by a single surgeon.
      Operative outcome was examined, including early mortality, morbidity, need for
      intensive (ICU) care and hospital length of stay (LOS). Percent of excess weight
      lost (EWL) and percent reduction of BMI after at least 1 year of follow-up were
      determined. Late mortality was assessed. RESULTS: There were 22 females and 12
      males with mean age 42.0 + 8.1 years and mean BMI 78.3 + 8.5 kg/m2. Obstructive
      sleep apnea (OSA) was found in 19/34 (58%) and hypoventilation syndrome of
      obesity (HSO) in 11/34 (32%). There was 1 early death (3 months) from renal
      failure. 7 patients (21%) developed complications, 3 major (pulmonary embolus,
      wound dehiscence) and 4 minor (wound infection). 16 patients (47%) required ICU,
      and 12 (35%) required extended mechanical ventilation. Hospital LOS was 10.3 +/-
      10.4 days for all patients. There were 4 late deaths (12%) from 7 to 36 months
      after RYGBP. Mean percent EWL was 61 +/- 17 and mean percent reduction in BMI was
      44 +/- 11. For those followed at least 36 months, weight loss was sustained in
      12/14 patients. CONCLUSIONS: RYGBP can be performed safely, even at the extremes
      of weight. While technically challenging, there were no instances of intra
      abdominal sepsis. Postoperative complications were few. Need for ICU and hospital
      LOS is greater, reflecting the incidence of pre-existing pulmonary problems.
      Weight loss is significant and appears to be sustained in most patients. Late
      deaths have been noted and deserve careful scrutiny.

PMID- 15946426
TI  - Laparoscopic Roux-en-Y gastric bypass is safe and effective in patients with a
      BMI > or =60.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been shown to be
      safe and effective. There is little data on the outcomes in massively super-obese
      patients, with a body mass index (BMI) > or =60 kg/m2 (super-super-obese). The
      goal of this study was to determine the safety and effectiveness of LRYGBP in
      these patients, and compare these results to patients with a BMI <60. METHODS:
      213 consecutive patients undergoing LRYGBP by a single surgeon at a university
      hospital were included in the study. The patients were divided into 2 groups: BMI
      <60 kg/m2 (n=167) and BMI > or =60 kg/m2 (n=46). The 2 groups were compared with
      regard to perioperative complications, and postoperative weight loss. RESULTS:
      Both groups had statistically similar complication rates. There were major
      complications in 8 patients (5%) in the lower BMI group and in 3 patients (7%) in
      the higher BMI group. There were minor complications in 9 patients (5%) in the
      lower BMI group and in 4 patients (9%) in the higher BMI group. Mean percent
      excess weight loss (%EWL) was 64% at 1 year in the BMI <60 group and 53% in the
      BMI > or =60 group. CONCLUSION: LRYGBP can be performed safely and effectively in
      super-super-obese patients (BMI > or =60). Although these patients have less %EWL
      than lighter patients, they still end up with a good result. Therefore, LRYGBP
      should be considered a good surgical option even for patients with a BMI > or
      =60.

PMID- 15946427
TI  - Nitrous oxide and laparoscopic bariatric surgery.
AB  - BACKGROUND: Nitrous oxide (N2O) is frequently used to supplement more potent
      anesthetic agents. One side-effect of N2O is its ability to expand an air
      containing space. We investigated if N2O adversely affected operating conditions
      by distending normal bowel during laparoscopic bariatric procedures. METHODS: 50
      morbidly obese patients were divided into 2 study groups. Group 1 patients were
      ventilated with a halogenated anesthetic/oxygen/air mixture, while Group 2
      received a halogenated anesthetic/oxygen/N2O mixture. At 30, 60, and 90 min
      intervals during the operation, the surgeon was asked if N2O was being used.
      RESULTS: The surgeons responded correctly only 42% (30 min), 50% (60 min), and
      48% (90 min) of the time. In Group 2 (N2O) patients, they incorrectly answered
      that N2O was not being used 88% (30 min), 68% (60 min), and 68% (90 min); and in
      Group 1 (air) patients, they incorrectly answered that N2O was being used 28% (30
      min), 32% (60 min), and 36% (90 min) of the time. CONCLUSION: We found that using
      N2O did not cause noticeable bowel distention during laparoscopic bariatric
      procedures of relatively short duration.

PMID- 15946428
TI  - Histologic variation of grade and stage of non-alcoholic fatty liver disease in
      liver biopsies.
AB  - BACKGROUND: Sampling error regarding disease grade and stage has been ascribed to
      needle liver biopsies in patients with chronic liver disease. Although several
      studies evaluating sampling error in liver biopsies exist, none have investigated
      this phenomenon in patients with non-alcoholic fatty liver disease (NAFLD). This
      study aims to determine the rate and extent of sampling error in liver biopsies
      obtained from patients undergoing Roux-en-Y gastric bypass (RYGBP) surgery for
      morbid obesity. METHODS: 10 morbidly obese patients underwent simultaneous liver
      biopsies from the right and left hepatic lobes during an open examination
      preceding the RYGBP procedure. The biopsies were subsequently randomly evaluated
      and then blindly re-evaluated by a liver pathologist. Degrees of inflammatory
      activity and fibrosis were determined and scored for each sample using a semi
      quantitative system with 3 grades and 4 stages. RESULTS: No grading differences
      were observed, and 3 patients (30%) had a difference of at least 1 stage between
      the right and left lobes. One patient had a 2-stage difference in paired samples,
      with significantly different biopsy sizes and number of portal tracts. Blinded
      histologic re-evaluation did not result in grading or staging scores that
      differed from the original evaluation. CONCLUSIONS: Liver biopsy samples taken
      from the right and left hepatic lobes showed similar grades of disease activity,
      but differed in histopathologic staging in 30% of the NAFLD patients. Obtaining
      an adequately sized biopsy (>1.0 cm in length with >10 portal tracts) greatly
      reduces sampling error.

PMID- 15946429
TI  - Lipid peroxidation in bariatric candidates with nonalcoholic fatty liver disease
      (NAFLD) -- preliminary findings.
AB  - BACKGROUND: Pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains
      incompletely known, and oxidative stress is one of the mechanisms incriminated.
      The aim of this study was to evaluate the role of liver oxidative stress in NAFLD
      affecting morbidly obese patients. METHODS: 39 consecutive patients with BMI >40
      kg/m2 submitted to Roux-en-Y gastric bypass were enrolled, and wedge liver biopsy
      was obtained during operation. Oxidative stress was measured by concentration of
      hydroperoxides (CEOOH) in liver tissue. RESULTS: Female gender was dominant
      (89.7%) and median age was 43.6 +/- 11.1 years. Histology showed fatty liver in
      92.3%, including 43.6% with nonalcoholic steatohepatitis (NASH), 48.7% with
      isolated steatosis and just 7.7% with normal liver. Liver cirrhosis was present
      in 11.7% of those with nonalcoholic steatohepatitis. Concentration of CEOOH was
      increased in the liver of patients with NASH when compared to isolated steatosis
      and normal liver (0.26+/- 0.17, 0.20+/- 0.01 and 0.14+/- 0.00 nmol/mg protein,
      respectively) (P < 0.01). Liver biochemical variables were normal in 92.3% of all
      cases, and no difference between NASH and isolated steatosis could be
      demonstrated. CONCLUSIONS: 1) Nonalcoholic steatosis, steatohepatitis and
      cirrhosis were identified in substantial numbers of morbidly obese patients; 2)
      Concentration of hydroperoxides was increased in steatohepatitis, consistent with
      a pathogenetic role for oxidative stress in this condition.

PMID- 15946430
TI  - Initial experience with Swedish adjustable gastric band at Saad Specialist
      Hospital, Al-Khobar, Saudi Arabia.
AB  - BACKGROUND: The aim of this study was to give an initial account of the weight
      loss and complications after applying the Swedish adjustable gastric band (SAGB)
      at Saad Specialist Hospital, Al-Khobar, Saudi Arabia. METHODS: From January 2001
      to December 2004, 140 consecutive patients (62% female) underwent SAGB. Mean
      initial body weight was 124.5 +/- 23.9 SD kg and BMI was 45 kg/m2 +/- 6.3 SD.
      Mean age was 37.9 (17-53). The pars flaccida technique was used for placement of
      the band. RESULTS: Mortality and conversion rates were 0. We had no
      intraoperative or short-term postoperative complications. Mean operating time was
      122 minutes (range 78-192), and hospital stay was 5 days. Followup ranged from 1
      to 30 months. Mean weight loss was 52 kg at 12 months and 75 kg at 30 months.
      Mean BMI fell to 29 kg/m2. CONCLUSION: With its safety and effectiveness, SAGB
      has been a good choice for the treatment of morbidly obese patients in our early
      experience.

PMID- 15946431
TI  - Effects of intragastric balloon on gastric emptying and plasma ghrelin levels in
      non-morbid obese patients.
AB  - BACKGROUND: Intragastric balloons have been proposed to induce weight loss in
      obese subjects. The consequences of the balloon on gastric physiology remain
      poorly studied. We studied the influence of an intragastric balloon on gastric
      emptying and ghrelin secretion in non-morbid obese patients. PATIENTS AND
      METHODS: 17 patients were included in the study, with mean BMI of 34.4 (range
      30.1-40.0). The balloon was inserted under general anaesthesia and endoscopic
      control, inflated with 600 ml saline, and removed 6 months later. Body weight and
      gastric emptying (13C-octanoic acid breath test) were monitored while the balloon
      was in place and 1 month after removal. Ghrelin levels were measured just before
      balloon insertion and removal. RESULTS: Mean weight loss was 8.7 kg (range 0-21).
      Gastric emptying rates were significantly decreased with the balloon in place,
      and returned to pre-implantation values after balloon removal. Plasma ghrelin
      levels were significantly decreased (95% CI: -3.8 to -20.7 ng/ml), despite
      concomitant weight loss. Weight reduction was not correlated to the effect of the
      balloon on gastric emptying, but was significantly correlated to the ghrelin
      variations (r=0.668, 95% CI: 0.212-0.885). CONCLUSIONS: Gastric emptying rates
      and plasma ghrelin levels are decreased in the presence of intragastric balloon.
      Weight loss induced by the intragastric balloon is related to ghrelin variations,
      but not to gastric emptying. Ghrelin inhibition may explain part of the effect of
      the balloon on satiety.

PMID- 15946432
TI  - Biliopancreatic diversion with duodenal switch combined with laparoscopic
      adjustable gastric banding.
AB  - BACKGROUND: The authors investigated the usefulness of an approach combining
      biliopancreatic diversion (BPD) with duodenal switch (DS) and laparoscopic
      adjustable gastric banding (LAGB) in morbidly obese patients. METHODS: 258
      morbidly obese patients underwent bariatric surgery. 80 underwent gastric bypass
      (GBP), with an 80-ml pouch, a 120-150-cm common channel and a 350-cm alimentary
      limb (Group 1). 178 underwent BPD combined with DS-LAGB (Group 2): an 80 cm
      common channel and a 200-cm alimentary limb were created in 68 patients (Subgroup
      2a); a 120-cm common channel and a 300-cm alimentary limb were created in 110
      patients (Subgroup 2b). Quality of life was assessed using the Moorehead-Ardelt
      Quality of Life Questionnaire (MA-QLQ). RESULTS: At 2 years, mean BMI and %EWL
      were 27.8 kg/m2 and 77.4 (Group 1), 25.2 kg/m2 and 99.6 (Subgroup 2a), and 27.6
      kg/m2 and 79.3 (Subgroup 2b), respectively. 4 GBP patients regained their weight
      2 years after surgery. There was 1 death, not related to surgery in Subgroup 2b.
      Preoperative MA-QLQ scores were similar between groups; at 2 years, MA-QLQ scores
      were higher in Subgroups 2a and 2b compared to Group 1 (+2.49 and +2.59 vs +0.98,
      respectively). CONCLUSION: Combination bariatric surgery is a safe, effective and
      durable weight loss option for the treatment of morbid obesity.

PMID- 15946433
TI  - Laparoscopic gastric bypass with silicone band in a pig model: prevention of
      anastomotic dilatation -- feasibility study.
AB  - BACKGROUND: Morbid obesity has become a major global health problem. Surgery
      remains the only effective treatment for patients with severe obesity, because
      diet reduction methods and pharmacologic agents have not resulted in long-term
      weight reduction. Gastric bypass (GBP) can provide adequate weight loss, but
      after some years, dilatation of the gastric pouch and outlet may lead to weight
      regain by allowing the patient to increase food intake. METHODS: 2 groups of 6
      pigs underwent laparoscopic GBP. In the first group, a non-adjustable silicone
      band (Proring-band, IOC, Innovative Obesity Care, Saint Etienne, France) was
      positioned 1 cm proximal to the gastrojejunal anastomosis. In the second group,
      the device used to stabilize the gastric pouch was an adjustable silicone band
      (Mid-band, Medical Innovation Developpement, Villeurbanne, France). Weight loss,
      complications and histological reaction were evaluated after 3 months. RESULTS:
      Mortality rate was 25% (cardiac arrythmia in 2 pigs). Conversion rate was 25%.
      The positioning of the band was more difficult with the Mid-band because of its
      larger size and the presence of the catheter. The average weight change in the
      Proring group was 15.8 kg (3.5-25.1 kg), and in the Mid-band group was 12.0 kg
      (6.2-15.1 kg). Morbidity consisted of one intragastric migration of the Proring
      band into the gastrojejunal anastomosis, and one infection of the port in the Mid
      band group treated by removal of the port and antibiotics. CONCLUSION: Use of
      silicone devices may be safe and effective in the prevention of pouch or outlet
      dilatation after GBP.

PMID- 15946434
TI  - Effects and mechanisms of implantable gastric stimulation on gastric distention
      in conscious dogs.
AB  - BACKGROUND: While implantable gastric stimulation (IGS) on the lesser curvature
      has been reported to induce weight loss in obese patients, its mechanisms
      involving gastric mechanical activity remain largely unknown. The aim of this
      study was to investigate the effect and mechanism of IGS on gastric tone in
      canines. METHODS: 8 healthy dogs were implanted with a gastric cannula on
      anterior stomach and a pair of electrodes at lesser curvature. Gastric tone was
      assessed with an electronic barostat in 2 randomized sessions, a control and a
      session with L-NNA (nitric oxide synthase inhibitor). The control session
      included 30 min baseline, followed by 30 min with IGS; the L-NNA session included
      30 min baseline, 30 min immediately after a bolus of L-NNA, and 30 min with IGS.
      RESULTS: 1) In the control session, IGS significantly increased the proximal
      gastric volume from baseline 91.3+/-7.1 ml to 186.3+/-27.1 ml (P<0.05); 2) L-NNA
      markedly reduced the proximal gastric volume from 110.3+/-11.9 ml to 56.9+/-10.8
      ml (P<0.01); and subsequent IGS did not significantly increase the proximal
      gastric volume (P>0.05). CONCLUSION: IGS significantly inhibits proximal gastric
      tone or induces gastric distention, and this inhibitory effect is mediated via
      the nitrergic pathway.

PMID- 15946435
TI  - Childhood sexual abuse is not associated with a poor outcome after gastric
      banding for severe obesity.
AB  - BACKGROUND: The aim of this study was to examine whether a history of childhood
      sexual abuse is associated with weight, health, and depression after Laparoscopic
      Adjustable Gastric Banding for severe obesity. METHODS: 157 patients (144 female,
      13 male) filled out questionnaires on average 34 months after surgery (range 8-68
      months). RESULTS: 23% of the participants, all women, reported a history of
      childhood sexual abuse. There were no differences between patients with and
      without a history of childhood sexual abuse on weight and physical health, but
      the group with a history of childhood sexual abuse showed a higher level of
      depression. CONCLUSION: A reported history of childhood sexual abuse does not
      appear to impact on weight outcome after bariatric surgery, but some patients may
      need additional psychological treatment for their mental health problems.

PMID- 15946436
TI  - Noncompliance with behavioral recommendations following bariatric surgery.
AB  - BACKGROUND: Bariatric surgery has been increasingly utilized for treatment of
      severe obesity. Although initial weight loss following surgery is almost
      completely assured, little is known about long-term out-come and patient
      compliance with post-surgical behavioral recommendations for diet and exercise
      that would improve outcome. The purpose of this study was to examine the rate of
      noncompliance with behavioral recommendations and to identify the incidence of
      psychological concerns following bariatric surgery. METHOD: Subjects were
      identified from an active clinical data-base of prospective clinical follow-up of
      all bariatric surgery patients. 100 consecutive patients who underwent Roux-en-Y
      gastric bypass were identified, and a chart review was conducted at 6 and 12
      months postoperatively to gather demographic data and identify the prevalence of
      noncompliance identified in monthly follow-up visits. Also, patients were asked
      about depression, relationship/sexual concerns, and medical complications.
      RESULTS: 81 women and 19 men were followed for 1 year. The majority of patients
      reported noncompliance in at least one area, with lack of exercise and snacking
      being most frequently cited (41%, 37% respectively overall). Most patients were
      compliant with eating protein first and avoiding sodas. At 12 months follow-up,
      12% reported depression, 4% reported sexual concerns and 2% reported relationship
      problems. Also, 9% reported having experienced some medical complication related
      to their surgery. CONCLUSION: Noncompliance with behavioral recommendations is
      pervasive following bariatric surgery, with lack of exercise being the most
      likely area of noncompliance. Because of the importance of compliance with
      behavioral recommendations for the successful outcome of bariatric surgery,
      further research is warranted to further clarify the factors that impact long
      term outcome and to design interventions to improve compliance.

PMID- 15946437
TI  - Psychosocial predictors of success following bariatric surgery.
AB  - BACKGROUND: Bariatric surgery is the treatment of choice for morbid obesity, but
      it does not lead to equal results in every patient. In addition to surgery, a
      number of non-surgical and psychological factors may influence patients' ability
      to adjust to the postoperative condition. Understanding the relationship between
      potential predictive variables and success after bariatric surgery will enable
      better patient selection, and the development of interventions to improve
      outcome. METHODS: A systematic literature search identified relevant variables,
      such as demography, preoperative weight, motivation, expectations, eating
      behavior, psychological functioning, personality, and psychiatric disorders,
      which may have predictive value for success after bariatric surgery. RESULTS:
      Greater success following bariatric surgery appears to occur in patients who are
      young and female, and have a high self-esteem, good mental health, a satisfactory
      marriage, and high socio-economic status, who are self-critical and cope in a
      direct and active way, are not too obese, were obese before the age of 18, suffer
      from and are concerned about their obesity, have realistic expectations and
      undisturbed eating behaviors. Occasionally, these variables may have poor or no
      predictive value. Although reliable predictors are lacking, most treatment teams
      propose their own exclusion criteria. CONCLUSION: The existing literature about
      potential predictors of success after bariatric surgery is far from conclusive;
      it is still uncertain which factors can predict success. Even where psychosocial
      functioning does not predict outcome, it is important to identify patients'
      characteristics which may be linked to their prognosis and to provide necessary
      pre- and postoperative psychosocial interventions.

PMID- 15946438
TI  - Factor V Leiden and postoperative deep vein thrombosis in patients undergoing
      open Roux-en-Y gastric bypass surgery.
AB  - BACKGROUND: Patients undergoing bariatric surgery are at risk for deep venous
      thrombosis (DVT) and fatal pulmonary embolus. In the presence of genetic
      hypercoagulable disorders, accepted methods of DVT prophylaxis utilizing
      sequential compression devices and subcutaneous unfractionated heparin may not be
      adequate to prevent DVT or fatal PE. METHODS AND RESULTS: 3 morbidly obese
      patients are described who underwent open Roux-en-Y gastric bypass and either had
      a previous diagnosis of Factor V Leiden or developed thrombosis in the presence
      of standard prophylaxis. Each was found to have the most common point mutation
      for Factor V Leiden, R506Q. All 3 patients had prophylactic inferior vena caval
      filters placed to prevent recurrent PE. CONCLUSION: The presence of venous
      thromboembolism either without known risk factors or in the presence of standard
      perioperative prophylaxis for DVT should warrant a hypercoagulable work-up.
      Inferior vena caval filter placement is indicated in the presence of a
      hypercoagulable disorder prior to surgical intervention in the morbidly obese
      population. The recent literature is reviewed.

PMID- 15946439
TI  - What we know and don't know about deep venous thrombosis and pulmonary embolism!

PMID- 15946440
TI  - Laparoscopic adjustable gastric banding prior to renal transplantation.
AB  - End-stage renal failure is most commonly caused by the obesity-related diseases,
      diabetes mellitus and essential hypertension, and is best treated with renal
      transplantation. Obesity may contribute to poor patient and graft survival, and
      is an exclusion criterion in some renal transplant programs. Diet and exercise
      programs have not proven to be effective for weight loss before transplantation,
      and bariatric surgery in any form has not been used in this setting before. We
      report three morbidly obese patients who underwent laparoscopic adjustable
      gastric banding to meet the criteria for renal transplantation and subsequently
      were successfully transplanted.

PMID- 15946441
TI  - Late gastric prolapse with pouch necrosis after laparoscopic adjustable gastric
      banding.
AB  - One of the most significant complications of the gastric banding procedure is
      gastric prolapse. However, pouch necrosis after gastric prolapse is an extremely
      rare complication. We present the case of a morbidly obese 41-year-old woman who
      had had a laparoscopic adjustable gastric banding procedure 3 years before. She
      developed a pouch necrosis after a late gastric prolapse. After failure of
      conservative treatment, a diagnostic laparoscopy was performed. This resulted in
      removal of the band and the diagnosis of pouch necrosis. A laparotomy was
      indicated and a sleeve gastrectomy was performed. A delay in the diagnosis of
      gastric prolapse can lead to major complications. Initial referral to a
      specialized center is necessary for proper care of this complication. Failure of
      conservative treatment mandates early operative intervention.

PMID- 15946442
TI  - Severe intra-abdominal infection due to Streptococcus Milleri following
      adjustable gastric banding.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding represents a safe and
      effective bariatric surgical method. Nevertheless, complications such as
      intraabdominal infections are associated with high morbidity and mortality. CASE
      REPORT: A 50-year old morbidly obese female patient underwent adjustable gastric
      banding with the Swedish band (SAGB). After an uneventful postoperative follow-up
      of 2 years, she developed band infection due to colon microperforation during
      endoscopic polypectomy. As the causative microorgansim, Streptococcus Milleri was
      revealed. Band removal was required, and recovery was quite prolonged.
      CONCLUSION: Intra-abdominal infection with Streptococcus Milleri can cause severe
      and life-threatening disease. Therefore, early diagnosis and surgical
      intervention combined with body weight adapted antibiotic therapy for a
      sufficiently long period of time seems necessary. In patients with intra
      abdominal implanted devices such as the SAGB who undergo endoscopic polypectomy,
      antibiotic prophylaxis should therefore be considered.

PMID- 15946443
TI  - Laparoscopic removal of gastric band after open banded gastric bypass.
AB  - Open banded gastric bypass has been the choice of some bariatric surgeons. This
      procedure includes a band (of various materials) around the gastric pouch. While
      there are advantages to this band, erosion and/or displacement of the band may
      occur. We describe a case of a symptomatic displaced band which was treated by
      laparoscopic removal. Laparoscopic removal of the band after open banded gastric
      bypass is feasible. Revision of previous bariatric surgery may be performed
      laparoscopically if the technical expertise is available.

PMID- 15946444
TI  - Topical benzocaine (Hurricaine) induced methemoglobinemia during endoscopic
      procedures in gastric bypass patients.
AB  - BACKGROUND: Methemoglobinemia results from oxidation of ferrous to ferric iron in
      hemoglobin. In addition to a functional anemia, methhemoglobinemia causes the O2
      binding affinity of the remaining O2 sites in the hemoglobin tetramer to
      increase; essentially shifting the oxyhemoglobin dissociation curve to the left
      and decreasing O2 delivery. Patients develop profound cyanosis unresponsive to O2
      when methemoglobin (MHb) levels exceed 10%. It can be lethal if levels exceed
      70%. Benzocaine 20% (Hurricaine) spray, commonly used in endoscopy (EGD) can
      cause methemoglobinemia. We report our experience. METHODS: Two patients out of
      >1,000 EGDs in 4 yrs developed methemoglobinemia. RESULTS: Patient 1: 34 F, BMI
      46, open distal gastric bypass. Patient 2: 26 F, BMI 49, laparoscopic proximal
      gastric bypass. Both had nausea and vomiting from stomal stenosis requiring EGD
      for which benzocaine 20% spray was used. Severe cyanosis (despite pulse oximetry
      readings of 86% and 89%), dyspnea and tachycardia, were seen within 13 and 7
      minutes. They were unresponsive to O2, despite being awake and conversant after
      complete reversal of sedatives. MHb levels were 35.6% and 18.8% (normal <1%).
      Patients dramatically improved after 1% methylene blue at 1-2 mg/kg IV over 5
      minutes. MHb levels dropped to 2.3% and 0.8 % within 150 and 110 minutes. Neither
      patient had any evidence of pulmonary embolism or DVT or G6PD deficiency.
      CONCLUSION: Topical benzocaine 20% (Hurricaine) spray used in EGDs gets absorbed
      and can cause methemoglobinemia. Sprays should be limited to 1 second. Prompt
      treatment with 1% methylene blue IV can be life-saving.

PMID- 15946445
TI  - Myasthenia gravis improvement after laparoscopic Roux-en-Y gastric bypass.
AB  - Many diseases in the obese population have been found to improve after weight
      loss. A 56-year-old female with a long history of myasthenia gravis (MG) and
      morbid obesity is reported. Preoperatively, she presented with a BMI of 46.5
      kg/m2, and was on three medications and IV immunoglobulin every 5 weeks. After
      the surgical procedure, she improved and required less medication. Because MG and
      morbid obesity require careful perioperative management in order to avoid
      complications, a multidisciplinary approach is recommended.

PMID- 15946446
TI  - Mounting the worldwide effort against obesity.

PMID- 15946447
TI  - The future of bariatric surgery.

PMID- 15946448
TI  - Radiological diagnosis of internal hernia after Roux-en-Y gastric bypass.
AB  - BACKGROUND: Internal hernia is a known complication of laparoscopic Roux-en-Y
      gastric bypass (LRYGBP). Preoperative diagnosis may be difficult on the basis of
      history and physical examination. CT scanning is often performed as a diagnostic
      tool for patients with symptoms after LRYGBP but is often read by the radiologist
      as non-specific or normal. Preoperative review of the study by the bariatric
      surgeon who is familiar with the neo-anatomy can identify the internal hernia and
      its location. METHODS: We retrospectively reviewed our first 185 patients
      undergoing LRYGBP to identify all patients who developed an internal hernia. The
      patient's symptoms, physical findings and CT scans were reviewed. Time to
      presentation with the internal hernia was noted. Radiological interpretation of
      the scans was recorded, as well as the bariatric surgeon's preoperative
      impression after review of the scans. RESULTS: In our initial experience of 185
      patients undergoing LRYGBP, 5 patients presented at various times in their
      postoperative course with an internal hernia, for an incidence of 2.7%. All
      patients underwent preoperative CT scanning. Radiologist interpretation of the
      scans identified one internal hernia of the 5 preoperatively and was suggestive
      in another. Preoperative review of the scans by the bariatric surgeon was not
      only highly suggestive of the diagnosis, but of the location as well, in all 5
      cases. CONCLUSION: Preoperative diagnosis of an internal hernia in patients after
      LRYGBP is often difficult. CT scanning has been found to be a very helpful
      diagnostic tool, especially when reviewed preoperatively by the bariatric
      surgeon.

PMID- 15946449
TI  - Laparoscopic sleeve gastrectomy is superior to endoscopic intragastric balloon as
      a first stage procedure for super-obese patients (BMI > or =50).
AB  - BACKGROUND: The treatment of patients with a BMI > or =50 kg/m2 is still
      controversial. Given the many co-morbidities and oftentimes fragile health of
      super-obese patients, surgeons experienced in bariatrics often advocate a less
      invasive first stage operation for these patients. This allows them enough weight
      loss to support a more major second-stage operation such as a gastric bypass or a
      biliopancreatic diversion/duodenal switch. Thus, the aim of this study was to
      compare laparoscopic sleeve gastrectomy (LSG) and the BioEnterics intragastric
      balloon (BIB) as a first-stage procedure for effective initial weight loss before
      more definitive surgery. METHODS: 20 patients (13 males and 7 females) who
      underwent LSG from May 2001 to December 2002 were compared with 57 patients (33
      males and 24 females) obtained as historical controls from two large series who
      underwent BIB. Patients were evaluated at 6 months in terms of: weight, BMI,
      percent of excess weight loss (%EWL) and change in BMI. RESULTS: There were no
      differences between groups for age, weight and BMI. There were no complications
      for patients under-going the LSG. For patients undergoing BIB, 4 patients (7%)
      had the balloon removed due to intolerance. The mean weight loss for patients
      undergoing LSG and BIB at 6 months was 45.5 vs 22.3 kg respectively, and the %EWL
      was 35 for LSG vs 24 for BIB. BMI decreased respectively from 69 to 53 for the
      LSG group and from 59 to 51 for the BIB group. Weight loss decreased co
      morbidities in 90% of patients after both procedures. CONCLUSION: Patients
      undergoing a LSG showed a faster and greater weight loss than those using a BIB
      at 6 months. Moreover, LSG is a safe procedure, with reproducible results, in
      contrast to the BIB which was tolerated by 93% of patients. The results indicate
      that both mean weight loss and %EWL were better in the LSG group, and that BMI
      decreased substantially more in the LSG group as well. Although the BIB procedure
      shows efficacy in reducing weight, the LSG group does so faster and to a greater
      amount, thus suggesting that this may be a superior procedure as a first stage
      for super-obesity.

PMID- 15946450
TI  - Association of super-super-obesity and male gender with elevated mortality in
      patients undergoing the duodenal switch procedure.
AB  - BACKGROUND: Previous studies have reported that risk factors for elevated
      mortality after Roux-en-Y gastric bypass include male gender, as well as a very
      elevated BMI. The present study was aimed at determining whether these same risk
      factors applied to patients undergoing the duodenal switch (DS) operation.
      MATERIALS AND METHODS: A retrospective chart review was performed of a cohort of
      385 patients who underwent DS. The 30-day mortality of super-superobese (SSO)
      patients [BMI > or =60 kg/m2 (n=102)] was compared with the mortality of the
      super- and morbidly obese (SMO) patients [35<BMI<60 kg/m2 (n=283)]. RESULTS:
      Overall mortality in SSO patients was 7.8% (8/102), compared with 0% (0/283) in
      SMO patients undergoing the same procedure (P<0.001). When a gender-based
      subgroup analysis was performed in the SSO patients, men had a 16.7% mortality
      (7/42) while women had only a 1.7% (1/60) mortality. CONCLUSIONS: In this study
      of patients undergoing DS, being SSO -- specifically SSO men -- was associated
      with increased mortality. Further studies will be needed to better determine the
      precise mechanism of these risk factors leading to such an elevation in
      mortality. Until then, caution should be exercised before performing DS in male
      patients with BMI > or =60 kg/m2.

PMID- 15946451
TI  - Permeability of the silicone membrane in laparoscopic adjustable gastric bands
      has important clinical implications.
AB  - BACKGROUND: The single most important attribute of the laparoscopic adjustable
      gastric band (LAGB) is its adjustability. Having the correct volume of fluid
      within the band is crucial for optimal performance. We observe a small reduction
      of the satiety-promoting effect with time. The characteristics and clinical
      relevance of volume change have not been adequately investigated. METHOD: One
      observer measured the saline volume within the 10-cm Lap-Band in 118 consecutive
      patients who fulfilled the entry criteria. The same observer had performed and
      recorded the previous adjustment. Initial volume, final volume and time between
      observations provide the data for analysis. In addition, a range of adjustable
      gastric bands currently available were bench-tested to assess broad applicability
      of findings. RESULTS: The difference between observations varied from 0.0 ml to 
      1.0 ml, median of -0.1 interquartile range (IQR) 0.0-0.2 ml. Two factors were
      associated with volume change: time in days between the observations (r = -0.55,
      P<0.001) and the initial volume within the band system (r = -0.50, P<0.001).
      These two independent factors accounted for a significant proportion of the
      variance observed (Cox and Snell R2 = 0.45, P<0.001). Replacement of any
      discrepancy appears to maintain effectiveness. All six bands showed similar
      saline loss when bench-tested. CONCLUSION: Adjustable gastric bands are
      semipermeable, leading to a small reduction in saline volume with time. Patients
      should be informed of this effect, attend for regular follow-up visits and seek
      help if the band's effectiveness appears reduced. We recommend that the volume
      present should be checked and readjusted at least every 6 months.

PMID- 15946452
TI  - Results of lap rebanding procedures after Lap-Band removal for band erosion -- a
      mid-term evaluation.
AB  - BACKGROUND: Late band erosion is an uncommon complication after laparoscopic
      adjustable gastric banding (LAGB). Overall erosion rate in our practice is
      approximately 1.6%. Our first 10 erosion patients underwent a rebanding procedure
      after previous Lap-Band removal. This study gives the results of midterm follow
      up. METHODS: 10 patients underwent Lap-Band removal for erosion. Then, 4 to 6
      months after band removal, between December 1999 and February 2002, the 10
      patients underwent LAGB again. Post-operatively, patients were seen at least
      every 3 months, and routine endoscopy was performed 1, 2 and 3 years after
      rebanding. Follow-up in this study was 36-63 (mean 48) months. RESULTS: No
      postoperative complications occurred; however, the first patient required
      conversion to laparotomy. Mean BMI was 40.6 (34-50) at the time of the initial
      LAGB, 34.3 (31-44) at the time of rebanding, and is 28.5 (22-38) at present.
      There have been 2 late complications: 1 pouch dilatation and 1 port leak. No re
      erosions have developed. Satisfaction has been excellent in 9 patients and
      moderate in 1. CONCLUSION: Laparoscopic rebanding is a safe, feasible, minimally
      invasive and efficacious option as a second bariatric procedure after Lap-Band
      removal for erosion. However, if the patient is not pleased with the first band,
      a different bariatric operation should be considered. Our results in the mid-term
      are excellent, but longer follow-up is necessary to draw definitive conclusions.

PMID- 15946453
TI  - Clinical and radiological follow-up of laparoscopic adjustable gastric bands,
      1998 and 2000: a comparison of two techniques.
AB  - BACKGROUND: Concerns still exist about the long-term effectiveness and rate of
      retention of the laparoscopic adjustable gastric band (LAGB). Furthermore,
      esophageal dilatation has been suggested as a long-term complication for LAGB. We
      therefore sought to objectively analyze our follow-up results in patients with
      LAGB performed in 1998 by perigastric technique and 2000 by pars flaccida
      technique. We also offered patients for 1998 a barium esophagram to assess
      dilatation. METHODS: Data on all 2,300 LAGBs performed since 1996 have been
      prospectively collected in LapBase. This data was accessed for 1998 and 2000, for
      follow-up complication, band removal, weight loss and comorbidity reduction.
      Patients were offered barium esophagrams. RESULTS: 123 patients (mean weight 127
      kg, mean BMI 44.5 kg/m2) had LAGB in 1998, and 162 patients (mean weight 123 kg,
      mean BMI 44) had LAGB in 2000. Follow-up was a mean 67 months in 88% for 1998 and
      94% at 34 months for 2000. Mean %EWL for 1998 was 51.2% with mean BMI 31.9.
      Slippage occurred in 9.5% in 1998 compared to 4.3% in 2000 (P<0.01). 20 of 23
      diabetics are off all treatment. 1 of 34 patients had esophageal dilatation on
      barium esophagram, which resolved on band deflation. CONCLUSION: LAGB is a safe
      and effective at midterm follow-up. Less slippage occurred after the pars
      flaccida technique. No evidence of permanent esophageal dilatation was found on
      barium studies.

PMID- 15946455
TI  - Short-term results of laparoscopic mini-gastric bypass.
AB  - BACKGROUND: The laparoscopic mini-gastric bypass (MGB) is a modification of
      Mason's loop gastric bypass, but with a long lesser curvature tube. With weight
      loss results similar to laparoscopic Roux-en-Y gastric bypass (LRYGBP), the MGB
      is a simpler operation with a low complication rate. Controversy exists
      concerning the efficacy and side-effects of this procedure. This report presents
      the technique of laparoscopic MGB and its results in 423 patients. METHODS: From
      October 2001 to October 2004, 423 consecutive patients (87 males and 336 females)
      underwent laparoscopic MGB (LMGB) for morbid obesity. Mean age was 30.8 years,
      preoperative mean weight 120.3 kg and mean BMI 44.2 kg/m2. RESULTS: All
      procedures were completed laparoscopically. Mean operative time was 130.8
      minutes, and mean hospital stay was 5.0 days. 18 minor early complications (4.3%)
      were encountered, and 7 major complications (1.7%) occurred. Marginal ulcers were
      noted in 34 patients (8.0%) during follow-up, and anemia was found in 41 patients
      (9.7%). Mean BMI decreased to 29.2 and 28.4 kg/m2 at 1-year and 2-year follow-up,
      with mean excess weight loss 69.3% and 72.2%. The Gastrointestinal Quality of
      Life Index improved significantly 1 year after the operation. CONCLUSIONS: LMGB
      has a low complication and mortality rate. The learning curve is less steep than
      for LRYGBP, whereas the efficacy is similar.

PMID- 15946454
TI  - Laparoscopic adjustable gastric banding: weight loss, co-morbidities, medication
      usage and quality of life at one year.
AB  - BACKGROUND: The objective of this study was to determine the weight loss, changes
      in co-morbidities, medication usage and general health status at 1 year after
      laparoscopic adjustable gastric banding (LAGB). METHODS: Prospective data were
      obtained from all subjects undergoing LAGB. These measurements included a medical
      history and review of systems, medications, height and weight and the SF-36
      general health survey. Patients were seen for band adjustments as needed
      throughout the year. At the 1-year follow-up visit, patients were weighed and
      interviewed about the status of their health conditions and their current
      medications, and the SF-36 was repeated. RESULTS: Between November 2002 and
      November 2003, 195 patients had LAGB. The majority of subjects were female
      (82.8%), married (65.1%), and white (94.9%). Complications occurred in 18
      subjects (9.2%). These included 3 slipped bands (1.5%), 4 port problems (2.1%), 8
      patients with temporary stoma occlusion (4.1%), 1 explantation (0.5%), and 1
      mortality (0.5%). Mean BMI decreased from 45.8 kg/m2 (+/- 7.7) to 32.3 kg/m2 (+/-
      7.0). Mean percent excess body weight lost was 45.7% (+/- 17.1) during the first
      year. Major improvements occurred in arthritis, asthma, depression, diabetes,
      gastro-esophageal reflux disease, hyperlipidemia, hypertension, joint and back
      pain, sleep apnea and stress incontinence. Medication usage declined remarkably.
      Quality of life (QoL) by the SF-36 showed highly significant improvements.
      CONCLUSIONS: At 1 year after LAGB, patients had experienced significant weight
      loss, resolution of comorbidities, decreases in medication usage, and
      improvements in QoL.

PMID- 15946456
TI  - Impedance cardiography: noninvasive assessment of hemodynamics and thoracic fluid
      content during bariatric surgery.
AB  - BACKGROUND: The effects of pneumoperitoneum (ppm) on hemodynamic parameters
      during bariatric surgery were investigated using the impedance cardiography
      monitor. METHODS: 11 patients with BMI 46.5+/-10 kg/m2 (range 38.9-60.8 kg/m2)
      underwent laparoscopic adjustable gastric banding under general anesthesia.
      Besides routine monitoring, the impedance cardiography (ICG) monitor was used to
      monitor cardiac output (CO), cardiac index (CI), systemic vascular resistance
      (SVR), and thoracic fluid content (TFC). Data were recorded at three stages: A)
      before ppm, B) during ppm, and C) after gas deflation. One-way analysis of
      variance (ANOVA) was used to analyze differences of the data before, during and
      after ppm, and post-hoc (Bonferoni test) for multiple comparisons of the data
      obtained. For all comparisons, P<0.05 was considered significant. RESULTS: There
      were significant low mean values of heart rate (HR), CO and CI at stage B
      compared to stage A (P<0.05). The mean values of TFC at stages A, B, and C were
      30.48 +/- 4.69, 29.74 +/- 2.86 and 31.72 +/- 4.93 k/Ohm respectively, with a non
      significant relationship (P>0.05). The mean values of SVR during the same stages
      A, B and C were 1299.18 +/- 374.40, 1873.64 +/- 276.26 and 1669.36 +/- 537.92
      dynes sec cm(-5) respectively, with significant high mean values at stages B and
      C compared to mean value at stage A (P<0.05). CONCLUSIONS: Morbid obesity and
      pneumoperitoneum have significant effects on hemodynamics. However, it appears
      that these changes were of marginal clinical significance.

PMID- 15946458
TI  - Hepatic histopathology of patients with morbid obesity submitted to gastric
      bypass.
AB  - BACKGROUND: The authors analyze and describe the hepatic histopathology of
      patients with morbid obesity submitted to gastric bypass. METHODS: A liver biopsy
      was performed in 112 patients at the beginning of gastric bypass, and clinical
      data (gender, age, BMI and associated diseases) were obtained from the patient
      records. RESULTS: Among the patients, 74.1% (n=83) were females and 25.9% (n=29)
      were males, age 39.59+/-10.12 years, with BMI 48.79+/-7.54. Regarding the
      diseases associated with morbid obesity, arterial hypertension was observed in
      67.9% (n=76) of the patients, joint diseases in 55.4% (n=62), dyslipidemia in
      40.2% (n=45), and diabetes type 2 in 27.7% (n=31). 111 patients (99.1%) showed
      different types of non-alcoholic fatty liver disease (NAFLD) (types 1, 2, 3 and
      4), with types 3 and 4 accounting for 57.7% (n=64). A significant association was
      observed between NAFLD type 4 and diabetes type 2 (P=0.018). The presence of
      glycogen nuclei was significantly correlated with steatosis (P=0.000), lobular
      inflammation (P=0.019) and perisinusoidal fibrosis (P=0.000). CONCLUSION: 1)
      Liver biopsy taken at gastric bypass reveals different types of NAFLD; 2)
      Diabetes type 2 is associated with NAFLD type 4; 3) Glycogen nuclei are
      correlated with steatosis, lobular inflammation and perisinusoidal fibrosis; 4)
      Steatosis represents the basic injury in NAFLD and is associated with hepato
      cellular ballooning. 5) In view of the frequency of hepatic alterations, a biopsy
      should be part of the surgical protocol of morbid obesity, this method being the
      only one able to determine the presence of lesions and to stage fibrosis.

PMID- 15946459
TI  - Morbid obesity, hypertensive disease and the renin-angiotensin-aldosterone axis.
AB  - BACKGROUND: Resistance to insulin and secondary hyperinsulinemia seem to be the
      putative link between morbid obesity (MO) and hypertensive disease (HD). Adipose
      tissue can secrete leptin and angiotensinogen, among other substances. Leptin
      activates the sympathetic nervous system, leading to HD. Angiotensinogen is a
      substrate for renin, therefore taking part in the renin-angiotensin-aldosterone
      axis and the regulation of blood pressure. In MO, both hypertrophy and
      hyperplasia of the adipocytes lead to an increase in the secretion of both
      substances, leading to loss of the equilibrium between the levels of both
      hormones. The aim of the present study was to evaluate these abnormalities and
      their potential reversibility following bariatric surgery. METHODS: Data from 100
      patients with MO was retrospectively evaluated. Anthropometric data, the plasma
      renin activity (PRA), plasma levels of aldosterone, ACE, potassium and sodium
      were collected both prior to surgery and 6, 12, 24 and 36 months after surgery.
      RESULTS: The waist-hip ratio (WHR) before surgery allowed classification of our
      patients in two groups: central obesity (WHR > or =0.90 in men and > or =0.85 in
      women); peripheral obesity (WHR <0.90 in men and <0.85 in women). In patients
      with central obesity, high levels of PRA, aldosterone and ACE with sodium
      retention and potassium loss and high insulin levels, were found. These changes
      were not found in patients with peripheral obesity. After gastric bypass, these
      abnormalities tended to disappear, mainly in the first 6 months. CONCLUSIONS: The
      reduction of BMI and WHR after gastric bypass confirmed this operation to be
      effective against MO. The high basal levels of insulin and the high rate of HD
      and diabetes in patients with central obesity seem to indicate that they suffer a
      metabolic syndrome with significant hormonal imbalances and sodium retention.
      Patients with peripheral obesity only showed a peripheral resistance against
      insulin, probably with a shorter duration of the hormonal action, but they did
      not show hormonal abnormalities or sodium retention. After gastric bypass these
      abnormal hormone levels tended to normalize.

PMID- 15946460
TI  - Psychiatric symptoms among prospective bariatric surgery patients: rates of
      prevalence and their relation to social desirability, pursuit of surgery, and
      follow-up attendance.
AB  - BACKGROUND: There is a very limited empirical literature regarding the
      psychiatric status of prospective bariatric patients and no studies that examine
      potential social desirability effects on self-presentation for this patient
      population. METHODS: The Psychiatric Diagnostic Screening Questionnaire (PDSQ)
      was utilized to assess the prevalence of 13 DSM-IV Axis I disorders in a sample
      of 294 bariatric patients attending a presurgical psychological consultation.
      Marlowe-Crowne Social Desirability Scale (MCSD) was also included for 256 of
      these patients. Six-month follow-up data for a sub-sample of 64 patients was
      obtained to compare the extent of presurgical psychiatric symptoms between
      individuals who did versus did not pursue the surgery and those who attended
      versus failed to attend post-operative follow-up appointments. RESULTS: The
      results suggested the presence of an Axis I disorder among half of these
      patients, with comorbidity present in 29.9% of the sample. Highest prevalence
      rates were suggested for somatization (29.3%), social phobia (18%),
      hypochondriasis (15%), and obsessive-compulsive disorder (13.6%). Univariate
      analyses revealed that only MSCD scores were significantly and negatively related
      to total symptom levels. Analyses of the follow-up data indicated that patients
      who pursued the surgery had fewer total symptoms. Patients who attended all of
      their follow-up appointments tended to be older and weighed more at their
      presurgical evaluation. CONCLUSION: These findings suggest that significant
      psychopathology can be found among bariatric patients, and highlight the
      importance of attending to impression management issues and anxiety spectrum
      disorders in presurgical psychological evaluations.

PMID- 15946461
TI  - The influence of eating behavior and eating pathology on weight loss after
      gastric restriction operations.
AB  - BACKGROUND: Eating behavior before surgery is considered to have great predictive
      value for the course of weight after surgery. The present study investigates the
      predictive value of three dimensions of eating behavior and disturbed eating on
      weight loss after gastric restriction surgery. METHODS: 149 patients consisting
      of 47 males (32%), 102 females (68%), with mean age 38.8+10.3 years, were
      investigated by means of a structured interview and the Three Factor Eating
      Questionnaire (TFEQ) before (T1) and at least 12 months after (T2) (14.0+1.5
      months) gastric restriction surgery. RESULTS: Mean BMI before surgery was 50.9+/
      8.1 kg/m2; postoperatively, the BMI decreased on average by 12.8 kg/m2 to 38.6+/
      6.8 kg/m2 (t=22.7, P=0.000) at T2. Point-prevalence of Binge Eating Disorder
      (BED) according to DSM-IV was 2.0%, and lifetime-prevalence 7.4%, respectively.
      Of our sample, 20.1% reported current binge episodes without fulfilling all
      criteria for BED. An eating pathology consisting of continual eating ("grazing")
      was reported in 19.5% of the patients. At T2, patients with a weight loss of at
      least 25% of their pre-surgery weight indicated significantly less hunger and
      disinhibition compared with patients with less weight loss. Patients with a
      distinct craving for sweets after surgery lost significantly less weight.
      Patients with binge episodes or "grazing" before surgery did not differ in
      average weight loss from patients without binge episodes or "grazing".
      CONCLUSION: Postoperative but not preoperative eating behavior is of predictive
      value for the extent of weight loss after gastric restriction surgery.

PMID- 15946462
TI  - Changes in insulin resistance following bariatric surgery and the adipoinsular
      axis: role of the adipocytokines, leptin, adiponectin and resistin.
AB  - The fat mass participates in the regulation of glucose and insulin metabolism
      through the release of adipocytokines in a mechanism called the adipoinsular
      axis. Putative adipocytokines include leptin, adiponectin and resistin. Obesity
      plays an important role in the pathogenesis of insulin resistance and type 2
      diabetes mellitus (T2DM). Bariatric surgery for morbidly obese patients leads to
      rapid and prolonged improvement in insulin resistance and T2DM in the vast
      majority of patients. We have previously proposed that the rapid improvement in
      insulin resistance observed following bariatric surgery is mediated by changes in
      incretin levels of the entero-insular axis and that long-term improvement is
      modulated by fat mass loss and changes in adipocytokine levels of the
      adipoinsular axis. In this review, we examine the information that supports a
      role of leptin, adiponectin and resistin in the development of insulin resistance
      and T2DM. Increasing levels of leptin and decreasing levels of adiponectin
      correlate with worsening insulin resistance in obese individuals. We also explore
      the relationship between changes in adipocytokines following bariatric surgery
      and long-term improvement in insulin resistance and T2DM. Leptin levels drop and
      adiponectin levels rise following laparoscopic adjustable gastric banding,
      gastric bypass and biliopancreatic diversion. These changes correlate with weight
      loss and improvement in insulin. Although resistin may play an important role in
      explaining insulin resistance, animal and human studies currently show
      conflicting results.

PMID- 15946463
TI  - "Right-angled" stapled latero-lateral duodenojejunal anastomosis in the duodenal
      switch.
AB  - A simplified technique to perform the duodeno-enteral anastomosis in the duodenal
      switch is presented. A linear stapled duodeno-jejunal side-to-side anastomosis is
      performed. The technique is easy and rapid to perform, avoids passing an anvil
      through the mouth of the patient and is safe for the patient, with satisfactory
      short-term results.

PMID- 15946464
TI  - Intestinal malrotation in a patient undergoing laparoscopic gastric bypass.
AB  - Intestinal malrotation is an anomalous disorder resulting from the incomplete
      rotation and fixation of the midgut during embryonic development. Although most
      patients present early in life with symptoms of bowel obstruction, others remain
      asymptomatic throughout their lives. We report the case of a 40-year-old morbidly
      obese woman with no significant past medical history, found to have intestinal
      malrotation on initial laparoscopic exploration for gastric bypass.

PMID- 15946465
TI  - Mirtazapine (Remeron) as treatment for non-mechanical vomiting after gastric
      bypass.
AB  - Two morbidly obese patients are reported who underwent gastric bypass and
      suffered nausea and vomiting 1 month after the operation. Endoscopy and upper GI
      series showed no evidence of stomal stenosis or other mechanical cause for a GI
      obstruction. Control of vomiting by current antiemetic drugs such as bromopride
      and ondansetrone was unsuccessful. The patients were then given Remeron Soltab
      (mirtazapine, Organon, Brazil) 30 mg once per day orally for 2 to 8 months.
      Nausea and vomiting disappeared within days after beginning the medication.
      Stomal stenosis is the main cause of vomiting after gastric bypass. After ruling
      out mechanical causes, other reasons for postoperative vomiting must be
      considered. Mirtazapine is a noradrenergic and specific serotonergic
      antidepressant, which blocks the 5HT3 receptor, leading to an antiemetic effect.
      It has successfully been used as an antiemetic drug in patients undergoing
      chemotherapy. We concluded that mirtazapine may be a successful option to treat
      non-mechanical postoperative vomiting in morbidly obese patients after gastric
      bypass.

PMID- 15946466
TI  - Complete regression of Barrett's esophagus after Roux-en-Y gastric bypass.
AB  - Regression of Barrett's esophagus may occur after effective anti-reflux surgery.
      Roux-en-Y gastric bypass (RYGBP) is an effective operation to treat morbid
      obesity. In addition, it provides complete relief of gastroesophageal reflux
      disease (GERD). Regression of Barrett's has not been reported after RYGBP. We
      performed a laparoscopic Roux-en-Y gastric bypass on a patient with GERD and
      Barrett's esophagus. At 1 year after the RYGBP, an upper endoscopy was performed
      as routine surveillance for the patient's Barrett's esophagus; endoscopic and
      histologic evaluation demonstrated complete regression of the Barrett's
      esophagus. The patient lost one-third of her preoperative weight and had
      resolution of her reflux symptoms. RYGBP limits the amount of acid reflux and
      completely diverts bile away from the esophagus. This may lead to the regression
      of Barrett's esophagus.

PMID- 15946467
TI  - Obesity and symptomatic achalasia.
AB  - Weight loss is a frequent finding in achalasia because of the difficulty in
      swallowing. Although manometric findings compatible with achalasia have been
      found in morbidly obese patients, all of them were asymptomatic. The authors
      report a case of symptomatic achalasia and morbid obesity in a 38-year-old woman.
      A mental disorder become manifested after the patient was submitted to an
      esophageal myotomy and fundoplication. With weight gain, postoperative
      gastroesophageal reflux developed. Drawbacks of further operative procedures in
      such a patient are discussed.

PMID- 15946468
TI  - Tachyarrhythmia due to atrial fibrillation in an intragastric balloon carrier:
      coincidence or consequence?
AB  - A morbidly obese patient is reported who underwent insertion of a BioEnterics
      Intragastric Balloon (BIB) as a pre-surgical procedure (ie. prior to restrictive
      gastric banding). While carrying the BIB, the patient suffered an episode of
      severe supraventricular tachyarrhythmia (atrial fibrillation). Although such an
      event is not definitely correlated to the BIB, the episode led us to modify the
      pre-treatment protocol, introducing dynamic Holter ECG into the work-up
      investigations and excluding subjects with a pathological cardiac rhythm.

PMID- 15946469
TI  - Drain erosion and gastro-jejunal fistula after one-anastomosis gastric bypass:
      endoscopic occlusion by fibrin sealant.
AB  - Leakage and fistula are feared complications after gastro-intestinal anastomosis.
      A 36-year-old female underwent an one-anastomosis gastric bypass. The 24-h
      routine radiological study before oral intake showed a tiny leak, which was
      treated by NPO and I.V. fluids. After 5 days, despite output reduction, total
      parenteral nutrition was commenced. After 8 days, the leak remained with reduced
      output. It was then occluded endoscopically by fibrin glue. To our surprise, we
      found the drain that we had left behind the anastomosis, inside the gastric
      pouch. We began withdrawing the drain and occluded the defect with 4 ml Tissucol.
      After 48-h of no output, a repeat radiological study showed persistence of the
      leak. 6 days later, a radiological study demonstrated total closure of the leak.

PMID- 15946470
TI  - [Inhibitory effect of lidamycin on growth of colon carcinoma 26 and hepatic
      metastasis in mice].
AB  - BACKGROUND & OBJECTIVE: Lidamycin (LDM, C-1027), an antitumor antibiotic
      containing a chromophore of enediyne structure, shows markedly cytotoxicities
      against cancer in vitro and in vivo. This study was to explore inhibitory effect
      of LDM on orthotopic transplanted tumors and hepatic metastasis of colon
      carcinoma 26 (C26) in mice. METHODS: A series of mice C26 models, including
      subcutaneous transplantation, orthotopic transplantation in cecum subserosa,
      intra-hepatic transplantation, and hepatic metastases after intra-splenic
      transplantation, were prepared and received intravenous injection of LDM 72 h
      after transplantation. Inhibitory rates of tumor growth and hepatic metastasis
      were calculated. LEICA QWINV3 image analysis system was used to determine the
      area of metastatic lesions in histopathologic sections. RESULTS: LDM at 0.025,
      0.05, and 0.1 mg/kg inhibited the growth of subcutaneous tumors by 64.8%, 78.2%,
      and 94.2%, orthotopic tumors by 57.5%, 71.5%, and 93.0%, intra-hepatic tumors by
      74.5%, 82.3%, and 92.8%, and intra-splenic tumors by 9.2%, 25.8%, and 70.2%,
      respectively. Determined by the numbers of metastatic nodules, LDM at 0.025,
      0.05, and 0.1 mg/kg inhibited hepatic metastases from intra-splenic
      transplantation by 34.6%, 50.7%, and 76.3%, and larger metastatic lesions (> 2
      mm) by 56.6%, 56.7%, and 90.8%, respectively. Evaluated by image analysis of
      metastatic lesions, LDM at 0.1 mg/kg inhibited hepatic metastases by 71.2%.
      CONCLUSION: LDM can inhibit growths of subcutaneous, orthotopic, and intra
      hepatic transplanted tumors and hepatic metastases of murine colon carcinoma 26.

PMID- 15946471
TI  - Inducing apoptosis of human nasopharyngeal carcinoma cell line CNE-2Z by bcl-xL
      short hairpin RNA.
AB  - BACKGROUND & OBJECTIVE: Recent studies showed overexpression of bcl-x(L) in human
      nasopharyngeal carcinoma (NPC) cell line CNE-2Z; it may play a pivotal role in
      tumorigenesis, metastasis, and drug resistance of NPC. This study was to explore
      inducing effect of bcl-x(L) short hairpin RNA (shRNA) on apoptosis of CNE-2Z
      cells. METHODS: After transfection of recombinant plasmid pmU6-RNAi expressing
      bcl-x(L) shRNA, apoptotic CNE-2Z cells were detected by fluorescent staining and
      flow cytometry (FCM). mRNA levels of bcl-x(L), bcl-2, survivin, and caspase-3 was
      detected by reverse transcription-polymerase chain reaction (RT-PCR); while
      protein levels of Bcl-x(L), Caspase-3, and P53 were detected by Western blot.
      RESULTS: When treated with pmU6-RNAi for 24 h, an obvious apoptotic peak of CNE
      2Z cells appeared; cell shrinkage, chromatin condensation, and nuclear
      fragmentation were observed in most cells under fluorescent microscope. RT-PCR
      analysis showed that pmU6-RNAi down-regulated mRNA levels of bcl-x(L), bcl-2, and
      caspase-3, but had little or no effect on mRNA level of survivin; Western blot
      analysis showed an obvious reduction in protein levels of Bcl-x(L) and Caspase-3,
      and a great increase in protein level of P53. CONCLUSIONS: bcl-x(L) shRNA can
      induce apoptosis of CNE-2Z cells, which may be closely related to down-regulation
      of bcl-2, caspase-3 and p53. bcl-x(L) shRNA may be helpful for developing gene
      therapy for NPC.

PMID- 15946472
TI  - [Correlations of telomere length and telomerase activity to radiosensitivity of
      human laryngeal squamous carcinoma cells].
AB  - BACKGROUND & OBJECTIVE: Many studies showed that telomere length and telomerase
      activity closely correlate with proliferation and malignant degree of tumor
      cells, and both of them might be involved in the repair of radiation-induced DNA
      damage. So it was speculated that telomere length and telomerase activity maybe
      correlate to radiosensitivity of carcinoma cells. This study was designed to
      investigate the correlations of telomere length and telomerase activity to
      radiosensitivity of human laryngeal squamous carcinoma cell line Hep-2. METHODS:
      Hep-2 cells were irradiated with 0, 2, 4, 8, or 12 Gy of gamma-ray for 3 times.
      Survival cells were subcultured for 20 generations. Radiosensitivity index,
      survival fraction at 2 Gy (SF(2)), was measured by clone formation assay.
      Telomere length (mean length of telomere restriction fragments, TRF) was examined
      by Southern blotu telomerase activity (TA) was detected by polymerase chain
      reaction-based telomeric repeat amplification protocol (PCR-TRAP) coupled with
      ELISA. RESULTS: After different doses of irradiation, SF(2) of Hep-2 cells was
      0.47-0.64; TRF was 3.76-9.43 kb; TA was 1.761-2.606. Each parameter had
      significant differences among the survival progenies (P<0.05). SF(2) was
      positively correlated with TRF (r=0.921, P<0.01), and negatively correlated with
      TA (r=-0.929, P<0.01); TRF was negatively correlated with TA (r=-0.944, P<0.01).
      CONCLUSION: Radiosensitivity of Hep-2 cells negatively correlates with telomere
      length, and positively correlates with telomerase activity, which suggest that
      both telomere length and telomerase activity may be used to predict cellular
      radiosensitivity.

PMID- 15946473
TI  - [Induction of active antitumor immune response by myeloma idiotype protein-pulsed
      dendritic cells].
AB  - BACKGROUND & OBJECTIVE: Most multiple myeloma (MM) patients could not be cured by
      high-dose chemotherapy and bone marrow transplantation. This study was designed
      to investigate in vitro killing effect of tumor-specific cytotoxic T lymphocytes
      (CTLs) stimulated by idiotype protein (Id)-pulsed dendritic cells (DCs) on
      autologous MM cells. METHODS: DCs were generated from peripheral blood monocytes
      of 6 MM patients using interleukin-4 (IL-4) and granulocyte-macrophage colony
      stimulating factor (GM-CSF). After cultured for 5 days, immature DCs were pulsed
      with Idu tumor necrosis factor-alpha (TNF-alpha) was added at the 7th day. Id
      pulsed DCs were cocultured with autologous T cells for 3 days to induce tumor
      specific CTLs. MTT assay was used to detect proliferation of autologous T cells,
      and evaluate killing effect of CTLs on autologous MM cells. RESULTS: Mature DCs
      were successfully induced. Id-pulsed DCs markedly increased proliferation of
      autologous T cells in a dose-dependent manner; stimulation index (SI) of Id
      pulsed DCs was the highest [(39.1+/-6.0)%] when the radio of DCs to T cells was
      10:1, which was significantly higher than those of unpulsed mature DCs [(19.3+/
      7.7)%], Id-pulsed immature DCs [(15.9+/-6.1)%], and unpulsed immature DCs
      [(11.4+/-4.9)%] (P < 0.01). Id-pulsed DCs induced anti-MM activity of CTLs in a
      dose-dependent manner. Unpulsed mature DCs also induced cytotoxicity of CTLs
      against autologous MM cellsu however, when DC:T was 30:1, killing rate of MM
      cells was significantly higher in Id-pulsed mature DCs group than in unpulsed
      mature DCs group [(70.1+/-7.9)% vs. (40.8+/-7.8)%,P < 0.05]. KRN7000-pulsed
      mature DCs stimulated proliferation of allogeneic T cells in a dose-dependent
      manner; when DC:T was 1:10, SI was significantly higher in KRN7000-pulsed mature
      DCs group than in unpulsed mature DCs group [(38.5+/-5.7)% vs. (20.2+/-5.7)%, P <
      0.05]. CONCLUSIONS: Mature DCs could be induced and Id with biological activity
      could be extracted from peripheral blood of MM patients. Id-pulsed DCs could
      induce antitumor immune response. KRN7000 could improve the immune function of in
      vitro cultured DCs.

PMID- 15946474
TI  - [In vitro induction of mature dendritic cells from malignant pleural effusions].
AB  - BACKGROUND & OBJECTIVE: Dendritic cells (DCs) can activate immunologic naive T
      cells to initiate antigen-specific immune responses. This study was to in vitro
      induce mature DCs from malignant pleural effusions of patients with lung cancer.
      METHODS: Malignant pleural effusions (500-1 000 ml) were collected from 16
      patients with primary lung cancer. Precursory DCs were obtained through density
      gradient centrifugation and magnetic cell sorting from malignant pleural
      effusions, and cultured with interleukin-4 (IL-4), granulocyte-macrophage colony
      stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha).
      Morphology of DCs was observed under invert optical microscope and electronic
      microscope; phenotype of DCs was analyzed by flow cytometry. Effect of DCs on
      proliferation of tumor infiltrative lymphocytes (TILs) was observed through mixed
      lymphocyte reaction (MLR). RESULTS: Mature DCs with typical morphology (elongated
      dendritic processions observed under invert optical microscope and electronic
      microscope) were induced from malignant pleural effusions. Expressions of surface
      phenotypes were higher in DCs induced for 48 h than in DCs induced for 0, 24, 96,
      and 192 h. When activated with DCs, proliferation of TILs was enhanced.
      CONCLUSION: Mature DCs could be induced from malignant pleural effusions of
      patients with lung cancer.

PMID- 15946475
TI  - [Correlation of immunophenotype to cytogenetics and clinical features of adult
      acute myeloid leukemia].
AB  - BACKGROUND & OBJECTIVE: New WHO classification has been rapidly used in diagnosis
      of leukemia. Based on coexpression and correlation of lineage-associated
      antigens, multiparameter high-resolution flow cytometry has been developed to
      precisely identify lineage characteristics of leukemia. Some immunophenotypes
      correlate with cytogenetic abnormality and prognosis. This study was to analyze
      immunophenotype of naive acute myeloid leukemia (AML), and explore its
      correlations to cytogenetics, clinical features, and FAB subtype of AML. METHODS:
      Multiparameter high-resolution flow cytometry with a panel of 25 different
      monoclonal antibodies was used to analyze the surface and cytoplasmic antigens
      expressions of 96 adults with AML; G-binding technique was used to analyze
      karyotype of 73 of the 96 patients. RESULTS: In these AML patients, some antigens
      were correlated with FAB subtypes:expression of CD2 was enhanced in AML-M3; HLA
      DR, CD34, and CD56 were absent in AML-M3; expression of CD19 was increased in AML
      M2; expressions of CD14 and CD56 were enhanced in AML-M5; MPO was absent in AML
      M0. Karyotype abnormality was detected in 40(54.8%) patients. CD22, CD56, and TdT
      expressions were correlated with karyotype abnormality. t(8; 21) was only
      detected in 10 AML-M2 patients with high expressions of CD15, CD19, CD34, and
      CD56; no lymphoid lineage antigens were detected in 7 AML-M3 patients with t (15;
      17). Expressions of CD4 and TdT were positively correlated with patient's age;
      expressions of CD7 and CD14 were positively correlated with high white blood cell
      count; expressions of CD4, CD14, and CD56 were positively correlated with high
      platelet count. CONCLUSIONS: The abnormal antigen expression of AML is tightly
      linked with karyotype abnormality. Detection of immunophenotype may help to
      diagnose and classify AML.

PMID- 15946476
TI  - [Leukemic bone marrow stromal cells in vitro protect leukemic cell line Jurkat
      cells from daunorubicin-induced apoptosis].
AB  - BACKGROUND & OBJECTIVE: Tumor microenvironment affects tumor cells growth. Bone
      marrow microenvironment may protect leukemic cells from drug-induced damages, but
      the mechanism is unclear. This study was to explore the protection of bone marrow
      stromal cells (BMSCs) on leukemic cells against chemotherapy and its mechanism.
      METHODS: Normal and leukemic BMSCs were isolated using Percoll, and cocultured
      with human acute lymphocyte leukemic cell line Jurkat cells in vitro. After
      treatment of 0.5 micromol/L of daunorubicin (DNR), apoptosis and cell cycle
      distribution of Jurkat cells were analyzed by flow cytometry. RESULTS: When
      treated with DNR for 24 h, apoptosis rate of normal BMSCs-cocultured Jurkat cells
      was significantly lower than that of Jurkat cells without coculture [(8.39+/
      4.08)% vs. (16.02+/-1.00)%, P < 0.05], and apoptosis rate of leukemic BMSCs
      cocultured Jurkat cells was significantly lower than that of normal BMSCs
      cocultured Jurkat cells [(5.73+/-1.78)% vs. (8.39+/-4.08)%, P < 0.05]; G(0)/G(1)
      phase percentage of BMSCs-cocultured Jurkat cells was significantly higher than
      that of Jurkat cells without coculture (P < 0.05), but the difference between
      Jurkat cells cocultured with normal and leukemic BMSCs was not significant (P >
      0.05). CONCLUSION: Leukemic BMSCs may inhibit DNR-induced apoptosis in leukemic
      cells partly through G(0)/G(1) phase arrest.

PMID- 15946477
TI  - [Gene expression profile of refractory acute myeloid leukemia (M2a)].
AB  - BACKGROUND & OBJECTIVE: Recurrence is the major cause of treatment failure of
      acute myeloid leukemia (AML). At recurrence, some patients show changes in
      immunophenotype and cytogenetics. Drug resistance, the main cause of
      refractoriness of AML, is related to abnormal genes expression. This study was to
      detect differential expression of genes in naive and recurrent/refractory AML,
      and explore potential mechanisms of recurrent/refractory AML. METHODS:
      Differential gene expressions of bone marrow mononuclear cells between naive and
      recurrent/refractory diseases in 5 self-paired patients with AML-M(2a) were
      detected by DNA microarray. RESULTS: In 925 tested genes, 14 were differentially
      expressed between naive and recurrent/refractory diseases in the 5 self-paired
      patients. Of the 14 genes, 12 (involved in signal transduction, DNA replication,
      regulation of transcription, RNA processing, and regulation of cell cycle) were
      obviously up-regulated in recurrent diseases, and up-regulation of RRM1 (involved
      in DNA replication) was the most obvious. CONCLUSIONS: Development of
      recurrent/refractory AML-M(2a) is concerned with various genes. Up-regulation of
      these genes suggests that proliferation of recurrent/refractory AML-M(2a) blasts
      may be higher than that of naive AML-M(2a) blasts.

PMID- 15946478
TI  - [Cloning tumor-related genes and tumor suppressor genes in glioma with polymerase
      chain reaction-based subtractive hybridization].
AB  - BACKGROUND & OBJECTIVE: Glioma is a common tumor in central nervous system with
      no specific clinical therapy. Its pathogenesis is unclear. This study was to
      clone tumor-related genes and tumor suppressor genes in glioma with polymerase
      chain reaction (PCR)-based subtractive hybridization, and to explore the
      molecular biological mechanism of tumorigenesis of glioma. METHODS: mRNA was
      isolated from a sample of human glioma, and reversely transcribed into cDNA. PCR
      based subtractive hybridization was used to clone tumor-related genes and tumor
      suppressor genes from it. RESULTS: In tumor-related candidate gene group, phospho
      protein enriched in astrocytes of 15 (PEA15) and homology of acid fibroblast
      growth factor (aFGF) were picked up. Whereas, in tumor suppressor gene group,
      interferon-induced protein 17 and ndr2 were picked up. ndr2 was widely expressed
      in normal brain tissue, but absent in glioma tissue. CONCLUSION: ndr2 gene is a
      candidate tumor suppressor gene, and may play a role in tumorigenesis of glioma.

PMID- 15946479
TI  - [Correlations of expressions of Glut1 and HIF-1alpha to cellular proliferation of
      colorectal adenocarcinoma].
AB  - BACKGROUND & OBJECTIVE: Malignant cells exhibit increased glucose metabolism and
      microenvironment hypoxia. Glucose transporter-1 (Glut1) and hypoxia-inducible
      factor 1 alpha (HIF-1alpha) enhance glucose metabolism under hypoxia. This study
      was to investigate the expressions of Glut1 and HIF-1alpha in colorectal
      adenocarcinoma, and explore their correlations to cell proliferation. METHODS:
      Immunohistochemistry was used to detect expressions of Glut1, HIF-1alpha, and
      proliferating cell nuclear antigen (PCNA) in 60 specimens of colorectal
      adenocarcinoma and 20 specimens of normal colorectal tissues. Their
      interrelations were analyzed. RESULTS: Positive rates of Glut1 and HIF-1alpha
      were significantly higher in colorectal adenocarcinoma tissues than in normal
      colorectal tissues (58.3% vs. 0, P < 0.01; 73.3% vs. 0, P < 0.01). PCNA level was
      significantly higher in colorectal adenocarcinoma tissues than in normal
      colorectal tissues (65.25+/-16.35 vs. 15.20+/-3.47, P < 0.01). Glut1 and HIF
      1alpha levels were positively correlated with PCNA level (r(1)=0.409, P < 0.01;
      r(2)=0.323, P < 0.05), and were associated with Dukes' stage and lymph node
      metastasis. CONCLUSIONS: The overexpressions of Glut1 and HIF-1alpha play
      important roles in carcinogenesis and progression of colorectal adenocarcinoma,
      and closely correlate with cell proliferation of colorectal adenocarcinoma.

PMID- 15946480
TI  - [Expression and significance of ADP-ribosylation factor 1 (ARF1) in colorectal
      laterally spreading tumor].
AB  - BACKGROUND & OBJECTIVE: Laterally spreading tumor (LST) behaves close to
      malignant tumor. This study was to search for the genes and functional proteins
      correlated to growth and development of colorectal LST (CLST), and to reveal the
      molecular mechanisms of CLST growth pattern and malignant transformation.
      METHODS: cDNA microarray was used to screen differentially expressed genes among
      CLST cell line and other 2 colorectal cell lines LoVo and SW480. Different mRNA
      and protein expressions of the genes were confirmed by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot. RESULTS: Compared with LoVo
      and SW480 cells, 58 genes were up-regulated and 39 genes were down-regulated in
      CLST cells. mRNA level of ADP-ribosylation factor 1 (ARF1) was significantly
      higher in CLST cells than in SW480 and LoVo cells (0.93 vs. 0.74 and 0.47, P =
      0.04); protein level of ARF1 was significantly higher in CLST cells than in LoVo
      cells. CONCLUSIONS: CLST has specific gene expression profile. ARF1 is
      overexpressed in CLST, and may mediate specific biological function of CLST.

PMID- 15946481
TI  - [Expression of cyclins in hepatocellular carcinoma and its correlation to tumor
      cell apoptosis].
AB  - BACKGROUND & OBJECTIVE: Cyclins overexpress in various tumors, but its expression
      in hepatocellular carcinoma (HCC) and its correlation to cell proliferation and
      apoptosis are unclear. This study was to determine the expression of Cyclins,
      proliferating cell nuclear antigen (PCNA), and cell apoptosis in HCC, and to
      analyze their interrelations. METHODS: Tissue microarray technology and SP
      immunohistochemistry were used to detect expressions of Cyclins A, B1, D1, E, and
      PCNA in 122 specimens of HCC. In situ terminal deoxyribonucleotide transferase
      labeling was used to detect cell apoptosis. RESULTS: In the 122 HCC specimens,
      positive rate of Cyclin A was 50.0%, of Cyclin B1 was 47.5%, of Cyclin D1 was
      42.6%, of Cyclin E was 35.2%. Cyclins levels were significantly higher in HCC
      tissues of grade II, III, and IV than in HCC tissues of grade I(P 0.05).
      Densities of apoptotic cells were significantly lower in HCC tissues of grade II,
      III, and IV than in HCC tissues of grade I(P 0.05); PCNA scores were
      significantly higher in HCC tissues of grade II, III, and IV than in HCC tissues
      of grade I(P 0.01). The poorer differentiation, the lower density of apoptotic
      cells in HCC, the higher PCNA score in HCC. Cyclins levels were negatively
      related to density of apoptotic cells (r=-0.686, P < 0.01), and positively
      related to PCNA score (r=0.599, P < 0.01); density of apoptotic cells was
      negatively related to PCNA score (r=-0.701, P < 0.01). CONCLUSION: Cyclins
      overexpress in HCC, which may shorten tumor cell cycle phase, accelerate cell
      proliferation and decrease apoptosis, and result in increased malignant
      phenotypes.

PMID- 15946482
TI  - Morphologic features of lymphatic in periphery region of gastric carcinoma and
      colon carcinoma.
AB  - BACKGROUND & OBJECTIVE: Most of the studies on lymphatic metastasis mechanism of
      carcinoma are confined to distribution of lymphatics. This research was to
      observe distribution and morphologic features of the lymphatics in periphery
      region of carcinoma, and morphologic changes of lymphatic endothelia. METHODS:
      Specimens were obtained from 10 patients with gastric carcinoma and 10 patients
      with colon carcinoma; 20 mice models bearing colon carcinoma were established.
      Morphology of lymphatics and ultrastructure of lymphatic endothelia were observed
      under microscope. Number density and volume density of lymphatics in periphery
      region of carcinoma and normal region were measured using computer image analysis
      system; open rate and destructive rate of lymphatics were calculated. RESULTS:
      The lymphatics in periphery region of carcinoma were dilated; their walls were
      disintegrated. Lymphatic endothelia were dissolved and destroyed into broken
      fragments; the organellae showed pathologic changes. Number density and volume
      density of lymphatics were significantly higher in periphery region of colon
      carcinoma than in normal region [(10.2+/-1.7)/mm(2) vs. (5.1+/-0.8)/mm(2), P <
      0.05u (1.5+/-0.2)% vs. (0.7+/-0.0)%, P < 0.05], and were significantly higher in
      periphery region of gastric carcinoma than in normal region [(8.0+/-0.9)/mm(2)
      vs. (3.4+/-0.6)/mm(2), P < 0.01; (1.6+/-0.3)% vs. (0.8+/-0.2)%, P < 0.05]. Open
      rate of lymphatics was significantly higher in periphery regions of mice model
      colon carcinoma, human gastric carcinoma, and colon carcinoma than in relevant
      normal regions (22.2% vs. 7.8%, 35.0% vs. 8.0%, and 25.8% vs. 5.0%, P < 0.05).
      Destructive rate of lymphatics was significantly higher in periphery regions of
      mice model colon carcinoma, and human gastric carcinoma than in relevant normal
      regions (20.1% vs. 0, and 35.3% vs. 2.0%, P < 0.05). CONCLUSION: Compare with the
      lymphatics in normal tissue, the lymphatics in periphery region of carcinoma
      tissue are dilated with disintegrated walls; the lymphatic endothelia are
      destroyed; the density of the lymphatics is increased.

PMID- 15946483
TI  - [Surgical treatment for liver metastasis of colorectal cancer: a report of 59
      cases].
AB  - BACKGROUND & OBJECTIVE: Liver metastasis is the major cause of treatment failure
      of colorectal cancer. The median survival time of patients with untreated liver
      metastases is only about 6 months. Surgical resection is the major treatment to
      prolong survival time of the patients. This study was to assess surgical
      treatment efficacy on these patients and their prognosis. METHODS: Records of 59
      colorectal cancer patients with liver metastases, treated with hepatectomy
      (including 14 cases of anatomical segmentectomy and 45 cases of wedge resection)
      from Jan. 1987 to Dec. 1998 in Cancer Hospital of Chinese Academy of Medical
      Sciences were reviewed. Postoperative complications occurred in 4 (6.8%)
      patients, without surgical death. Survival rate was estimated by Kaplan-Meier
      method, and compared by log-rank test. Prognostic factors were analyzed by
      multivariate Cox regression model. RESULTS: The overall 1-, 3-, and 5-year
      survival rates were 91.4%, 34.8%, and 21.9%. Survival rate was significantly
      lower in patients with heterochronia metastasis than in patients with synchronal
      metastasis (P < 0.05), and lower in patients with metastasis size of > 5 cm than
      in patients with metastasis size of < or = 5 cm. Univariate analysis showed that
      time of liver metastasis and metastasis size of > 5 cm were prognostic factors (P
      < 0.05); while node status of primary tumor, number of liver tumors, and
      carcinoembryonic antigen level had no significant relations with prognosis (P <
      0.05). CONCLUSIONS: Hepatectomy may prolong survival time of colorectal cancer
      patients with liver metastases. Early diagnosis with intensive follow-up is
      crucial to increase the resectability of liver metastasis.

PMID- 15946484
TI  - [Infiltration length of gastric cancer on giant sections].
AB  - BACKGROUND & OBJECTIVE: The resection boundary for gastric cancer is
      controversial. The study was designed to investigate gastric wall infiltration
      length of gastric cancer. METHODS: A total of 105 patients with gastric cancer
      who underwent gastrectomy at Cancer Center of Sun Yat-sen University from Apr.
      2002 to Feb. 2004 were eligible. During gastrectomy, gastric wall lengths of 18
      patients before traction (L1), after traction (L2), and after isolation (L3) were
      measured. Longitudinal specimen along the center of gastric cancer was fixed to
      measure the lengths of proximal and distal margins to the cancer. Giant section
      was observed under microscope to calculate the true infiltration length in
      proximal and distal margins according to the principle of the length changing
      uniformity. RESULTS: In the 18 specimens, L2 was significantly longer than L1 and
      L3 (P < 0.05); no significant difference was showed between L1 and L3 (P > 0.05).
      The infiltration length of localized gastric cancer, including early stage
      cancer, Borrmann I type cancer, and Borrmann II type cancer, was less than 2 cmu
      that of invasive gastric cancer, including Borrmann III type cancer and Borrmann
      IV type cancer, was less than 5 cm. CONCLUSION: The resection length for
      localized gastric cancer is at least 2 cm to tumor margin, and for invasive
      gastric cancer is at least 5 cm to tumor margin.

PMID- 15946485
TI  - [Stereotactic radiotherapy for multiple brain metastases].
AB  - BACKGROUND & OBJECTIVE: Stereotactic radiotherapy (SRT) has obvious advantages in
      treating intracranial tumors, but there are few reports about application of SRT
      to multiple intracranial tumors. This paper summarized the therapy outcome of
      patients with multiple brain metastases, and evaluated the efficacy and
      application of SRT. METHODS: Clinical data of 136 patients with multiple brain
      metastases received radiotherapy from Jun. 1996 to Dec. 2002 were reviewed. Of
      the 136 patients, 52(38.2%) received conventional radiotherapy alone (CR group),
      84(61.8%) received SRT or SRT plus whole brain radiotherapy (SRT group). RESULTS:
      Clinical effective rate, and elimination rate of brain metastases (diameter of >
      20 mm) were significantly higher in SRT group than in CR group (96.4% vs. 86.5%,
      P=0.02; 70.4% vs. 36.0%, P=0.007). Persistent brain edema rate was 8.3% in SRT
      group, and 9.6% in CR group (P=0.767). Intracranial tumor recurrence rate was
      25.0% in SRT group, and 19.4% in CR group (P=0.653). Median survival time was
      significantly longer in SRT group than in CR group (10.5 months vs. 6.5 months,
      P=0.014); 1-year survival rate was significantly higher in SRT group than in CR
      group (40.5% vs. 21.2%, P=0.023). CONCLUSION: Reasonable application of SRT could
      improve life quality and treatment outcome of patients with multiple brain
      metastases, reduce intracranial tumor recurrence and radiation damage, and
      prolong patients'survival time.

PMID- 15946486
TI  - [Extramedullary plasmacytoma in the head and neck: a report of 10 cases and
      literature review].
AB  - BACKGROUND & OBJECTIVE: Extramedullary plasmacytoma (EMP), a rare tumor, often
      appears in the head and neck region. About 80% of EMPs occur in the submucosa of
      the upper aerodigestive tract. On both clinical presentation and pathologic
      examination, these tumors may be confused with some common tumors in the head and
      neck. This study was to evaluate clinical feature, diagnosis, and treatment of
      EMP in the head and neck. METHODS: Clinical data of 10 consecutive patients with
      pathologically confirmed EMP in the head and neck, treated in our hospital from
      Jan. 1977 to Dec. 2003, were reviewed. Of the 10 patients, 2 underwent surgery
      alone, 2 underwent surgery plus adjuvant radiotherapy,4 received radical
      radiotherapy, 1 received radical radiotherapy plus adjuvant chemotherapy, and 1
      gave up treatment. RESULTS: The patients mainly manifested as local masses and
      relevant symptoms. Of the 3 patients received immunohistochemical staining to
      detect IgG, 1 was lambda type, and 2 were kappa type. Six patients received Bence
      Jones protein detection, and 4 patients received serum myeloma protein detection;
      all of them showed negative results. Bone marrow biopsy was made in 4 patients,
      skeletal survey was made in 4 patients; all results were normal. By the end of
      follow-up (Mar. 2003), 6 patients were still alive (5 patients survived for more
      than 1 year, 3 of the 5 patients survived disease-freely for more than 15 years);
      1 died of local recurrence 2 years after diagnosis; 1 died of multiple myeloma; 1
      died of heart disease before treatment; 1 lost follow-up. CONCLUSIONS: The
      diagnosis of EMP mainly depends on clinical manifestation and pathologic results.
      Radiotherapy and surgery are the main treatments for EMP in the head and neck.

PMID- 15946487
TI  - [Application of heimlich valve drainage to interventional procedure-induced
      pneumothorax in cancer patients: a report of thirteen cases].
AB  - BACKGROUND & OBJECTIVE: Pneumothorax, usually pure pneumothorax, often occurs
      during interventional procedures (such as biopsy and percutaneous lung cancer
      radiofrequency ablation) applied in cancer patients. Traditional treatment of
      pneumothorax uses a thoracic drainage tube connected to an underwater seal
      device, and patient needs hospitalization for its huge trauma. Heimlich valve has
      been used in thoracic drainage for years abroad. This study was to investigate
      the clinical value of Heimlich valve drainage for interventional procedure
      induced pneumothorax in cancer patients. METHODS: Heimlich valve connected to a
      chest catheter was used in treating interventional procedure-induced pneumothorax
      in 13 cancer patients from Mar. 1999 to Feb. 2003. RESULTS: Of the 13 patients, 6
      accepted inpatient management, and 7 accepted outpatient management. The
      pneumothoraxes of all patients were disappeared 2-3 days after drainage, and the
      lungs were re-expanded well. No complications occurred. CONCLUSIONS: Heimlich
      valve pneumothorax drainage is micro-invasive, easy to perform, and safe, and can
      be managed in outpatient. It also can achieve good clinical results, and should
      be recommended when pneumothorax occurs during interventional procedure.

PMID- 15946488
TI  - [Changes of visual field and visual evoked potential in nasopharyngeal carcinoma
      patients after radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Radiotherapy is the main treatment for nasopharyngeal
      carcinoma (NPC). The incidence of radiation-induced complications, especially
      radiation optic neuropathy (RON), increases along with prolonging survival time
      of the patients. This study was to investigate RON in NPC patients after
      irradiation by visual field and visual evoked potential (VEP) tests. METHODS: A
      total of 28 NPC patients, who underwent conventional external-beam irradiation,
      received visual field and VEP tests before irradiation, at the end of
      irradiation, and 5 years after irradiation. RESULTS: Thirty-four (60.7%) eyes in
      21 patients developed pathological visual field; 15 (44.1%) of these 34 eyes
      occurred within 10-24 months after irradiation. Of the 34 eyes, 8 showed
      concentric visual field constriction; 6 showed bitemporal hemianopia; 8 showed
      local photosensitivity descend; 10 showed central or cecocentral scotoma; 2
      showed scotoma enlargement. Forty-four (78.6%) eyes in 26 patients appeared VEP
      abnormity; 24 (54.5%) of these 44 eyes occurred within 14 months after
      irradiation. In small, medium, and large elements, VEP latencies were
      significantly longer within 1 year after irradiation than pre-irradiation (P <
      0.001, P < 0.001, and P=0.001); VEP amplitudes were lower within 1 year after
      irradiation than pre-irradiation without significant difference (P=0.249,
      P=0.940, and P=0.450). One year after treatment, VEP latency delay maintained in
      each element (P=0.004, P < 0.001, P < 0.001); VEP amplitudes were decreased
      (P=0.002, P=0.189, P < 0.001). The incidence of pathologic visual field was
      significantly lower in patients received irradiation of < or =70 Gy than in
      patients received irradiation of > 70 Gy (50.0% vs. 77.3%, P=0.041). CONCLUSIONS:
      RON correlates to total irradiation dose. Pathologic visual field may indicate
      the position of RON.

PMID- 15946489
TI  - [Impact of pre-radiotherapy hemoglobin level on local control of nasopharyngeal
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Oxygen increases tumor sensitivity to radiotherapy; tumor
      hypoxia is more prevalent in tumor patients with pretreatment hemoglobin
      concentration of < 130 g/L. This study was to evaluate impact of pre-radiotherapy
      hemoglobin level on radiotherapy outcome of nasopharyngeal carcinoma (NPC)
      patients. METHODS: Clinical and follow-up data of 166 NPC patients received
      definitive radiotherapy from 1999 to 2000 were reviewed. Pre-radiotherapy
      hemoglobin levels were stratified as high (> or =130 g/L) and low (< 130 g/L).
      Cox regression analysis was used to determine factors affecting local control.
      RESULTS: The median pre-radiotherapy hemoglobin level of the 166 patients was 135
      (85-189) g/L. Hemoglobin was < 130 g/L in 68 (41%) patients, and > or =130 g/L in
      98 (59%) patients. The pre-radiotherapy hemoglobin level of < 130 g/L was related
      to low 3-year local relapse-free survival rate (78% vs. 90%, P=0.015), but had no
      relations with distant metastasis-free survival (75% vs.77%, P=0.763) and overall
      survival rates (73% vs. 83%, P=0.056). Multivariate analysis showed that pre
      radiotherapy hemoglobin level, T stage, and gender were independent prognostic
      factors for local failure. CONCLUSIONS: Pre-radiotherapy hemoglobin of < 130 g/L
      is a prognostic factor for local control of NPC. Strategies for maintaining pre
      radiotherapy hemoglobin of > or =130 g/L before radiotherapy and during treatment
      should be further explored.

PMID- 15946490
TI  - [Multivariate prognostic analysis for patients with unresectable esophageal
      carcinoma after concurrent chemoradiotherapy].
AB  - BACKGROUND & OBJECTIVE: Concurrent chemoradiotherapy is recommended as standard
      treatment for unresectable esophageal carcinoma now. This study was to analyze
      the prognostic factors of unresectable esophageal carcinoma after concurrent
      chemoradiotherapy. METHODS: A total of 132 unresectable esophageal carcinoma
      patients received concurrent chemoradiotherapy from Jan. 1996 to Dec. 2003 in our
      hospital. All patients received chemotherapy at the beginning of radiotherapy,
      and when the radiation dose escalated to 40 Gy. Total dose of irradiation was 60
      70 Gy. Gender, age, disease course, focus location, swallow embarrassment, weight
      loss, Karnofsky's performance status (KPS) score, family history, hemoglobin (HB)
      before therapy, X-ray type, pathologic grade, focus length, TNM stage,
      irradiation method and technology, irradiation dose, radiotherapy interval, short
      term effect, esophagus perforation, esophagus haemorrhage, and retreatment
      methods were used as analysis factors for Cox regression univariate and
      multivariate analyses. RESULTS: Univariate analysis showed that diseases course,
      focus location, weight loss, M stage, short-term effect, esophagus perforation,
      esophagus haemorrhage, and retreatment methods were prognostic factors of these
      patients. Multivariate analysis showed that M stage [P=0.014, odds ratio
      (OR)=2.515], short-term effect (P < 0.001, OR=2.181), esophagus perforation
      (P=0.022, OR=3.266), and retreatment methods (P=0.026, OR=1.142) were independent
      prognostic factors. CONCLUSION: The main prognostic factors of the patients with
      unresectable esophageal carcinoma treated with concurrent chemoradiotherapy are M
      stage, short-term effect, esophagus perforation, and retreatment methods.

PMID- 15946491
TI  - [Expression and clinical significance of cytokeratin 19 in bone marrow of
      patients with breast cancer].
AB  - BACKGROUND & OBJECTIVE: Breast cancer may undergo metastasis in early phase.
      Distant metastasis, especially bone metastasis, may influence prognosis of breast
      cancer patients. Bone marrow micrometastasis (BMM) is difficult to detect with
      routine methods. This study was designed to evaluate expression and clinical
      significance of cytokeratin 19 (CK19) in bone marrow of patients with breast
      cancer. METHODS: Expression of CK19 mRNA in bone marrows of 65 breast cancer
      patients, 15 benign breast disease patients, and 8 healthy volunteers was
      detected by reverse transcription-polymerase chain reaction (RT-PCR). Correlation
      of CK19 mRNA expression to clinicopathologic features of the 65 breast cancer
      patients was analyzed. RESULTS: Positive rate of CK19 mRNA was 33.8% in the 65
      breast cancer patients, and 0 in both benign breast disease patients and healthy
      volunteers. Expression of CK19 mRNA was positively correlated with tumor size and
      clinical stage (P < 0.05), but was not related to age and lymph node status (P >
      0.05). In addition, positive rate of CK19 mRNA was positively correlated with
      carcinoembryonic antigen (CEA) in peripheral blood (r=0.372, P=0.002).
      CONCLUSIONS: CK19 mRNA may be used as a molecular marker to detect bone marrow
      micrometastasis in patients with breast cancer. The detection may help to select
      proper therapy and predict prognosis of breast cancer patients.

PMID- 15946492
TI  - [Correlations of serous levels of matrix metalloproteinases (MMP-2 and MMP-9) to
      invasion and metastasis of papillary thyroid carcinoma].
AB  - BACKGROUND & OBJECTIVE: Papillary thyroid carcinoma is a common carcinoma in
      thyroid without ideal hematological biomarkers to indicate its biological
      feature. This study was to explore the correlation of serous levels of matrix
      metalloproteinases (MMP-2 and MMP-9) to invasion and metastasis of papillary
      thyroid carcinoma. METHODS: Serous levels of MMP-2 and MMP-9 of 74 patients with
      pathologically confirmed papillary thyroid carcinoma were measured by zymography.
      All patients were treated with modified radical operation in the Second
      Affiliated Hospital of Wenzhou Medical College from 1999 to 2003. RESULTS: Serous
      levels of activated MMP-2 and MMP-9 were significantly higher in patients with
      lymph node metastases than in patients without lymph node metastases (71.9+/-11.7
      vs. 35.2+/-6.6, P < 0.001; 15.5+/-6.1 vs. 7.3+/-2.3, P < 0.001), and were
      significantly higher in patients with carcinoma invaded in and through integument
      than in patients with carcinoma invaded within integument (70.5+/-13.0 vs. 35.4+/
      7.9, P < 0.001; 14.7+/-6.1 vs. 8.0+/-4.2, P < 0.001). There was no significant
      difference in serous levels of activated MMP-2 and MMP-9 between patients with
      carcinoma diameter of > or =1 cm and < 1 cm (55.4+/-20.4 vs. 59.3+/-20.8, 10.8+/
      5.7 vs. 13.7+/-6.8). There was also no significant difference in serous levels of
      total MMP-2 and MMP-9 between every 2 groups mentioned above (P > 0.05).
      CONCLUSION: Serous levels of activated MMP-2 and MMP-9 relate with invasion and
      metastasis of papillary thyroid carcinoma, but not relate with tumor size.

PMID- 15946493
TI  - [Correlation of clusterin expression to prognosis of bladder carcinoma].
AB  - BACKGROUND & OBJECTIVE: Clinically, molecular prognostic markers for bladder
      carcinoma are still rare. Recently, up-regulation of clusterin protein has been
      suggested to relate with development and prognosis of several human cancers, but
      its relation with bladder cancer is unclear. This study was to analyze
      correlation of expression of clusterin protein to clinicopathologic parameters
      and prognosis of bladder cancer with tissue chip. METHODS: A tissue microarray
      containing 81 cases of bladder carcinoma was constructed. The expression of
      clusterin was detected by immunohistochemistry; its correlation with
      clinicophathologic parameters was analyzed. RESULTS: Of the 81 cases of bladder
      cancer, 69 were detectable by immunohistochemistry, 32 (46.4%) of which showed
      overexpression of clusterin protein. Overexpression rate of clusterin was
      significantly higher in poorly differentiated (G3 grade) tumors than in well
      differentiated (G1-G2 grades) tumors (75.0% vs. 34.7%, P=0.002), and was
      significantly higher in invasive (T2-T4 stages) tumors than in superficial (Ta-T1
      stages) tumors (65.4% vs. 34.9%, P=0.014). Expression of clusterin was negatively
      correlated with prognosis of bladder cancer patients (log-rank=5.88, P=0.015);
      the recurrence-free survival time of patients with overexpression of clusterin
      was shorter than that of patients with normal expression of clusterin (37.3
      months vs. 48.8 months). CONCLUSION: The overexpression of clusterin might be a
      molecular prognostic marker of bladder cancer.

PMID- 15946494
TI  - [Possibility of PTEN expression on predicting pathologic risk factors of
      endometrioid adenocarcinoma before operation].
AB  - BACKGROUND & OBJECTIVE: Fully estimating pathologic risk factors is important for
      selecting operation and predicting prognosis for endometrioid adenocarcinoma.
      Phosphatase and tension homology deleted on chromosome ten (PTEN), taken as the
      housekeeping gene of endometrium, has the highest mutation rate in endometrioid
      adenocarcinoma. This study was to investigate the effect of PTEN on predicting
      pathologic risk factors of endometrioid adenocarcinoma before operation. METHODS:
      Clinicopathologic data of 107 patients with endometrioid adenocarcinoma were
      retrospectively analyzed. The expression of PTEN was detected by SP
      immunohistochemistry. Correlations of PTEN to high risk factors, such as
      differentiation, myometrium invasion, and lymphatic metastasis, were analyzed.
      RESULTS: Deletion rate of PTEN was 56.1% in the 107 endometrioid adenocarcinoma
      patients. PTEN expression had no correlations to histological differentiation
      (P=0.695), myometrium invasion (P=0.921), lymphatic metastasis (P=0.682),
      surgical stage (P=0.750), estrogen receptor (P=0.281), and progestin receptor
      (P=0.260). CONCLUSION: Detection of PTEN can't predict the high risk factors of
      endometrioid adenocarcinoma before operation.

PMID- 15946495
TI  - [Recurrence risk factors of platinum-sensitive epithelial ovarian cancer].
AB  - BACKGROUND & OBJECTIVE: The prognosis of platinum-sensitive ovarian cancer
      patients was better than that of chemoresistant ones. However, platinum-sensitive
      ovarian cancer patients still have a high recurrence rate, which affects their
      prognosis. This study was designed to analyze clinical features and recurrence
      risk factors of platinum-sensitive epithelial ovarian cancer. METHODS: Factors
      that might relate to recurrence of 90 platinum-sensitive epithelial ovarian
      cancer patients, admitted in Cancer Center of Sun Yat-sen University from 1993 to
      1999, with complete remission of more than 6 months, were assessed. Univariate
      analysis was performed using Chi(2) test; while multivariate analysis was carried
      out using Cox proportional hazard model. RESULTS: Among the 90 patients,
      36(40.0%) relapsed with the median recurrence-free interval of 20 months. Pelvic
      cavity (18/36, 50.0%) was the most frequently involved. The 3-and 5-year survival
      rates of all patients were 79.6% and 69.5%; while those of the recurrent ones
      were 62.3% and 39.6%. Univariate analysis showed that the early FIGO stage group,
      mucinous type group, and no neoadjuvant chemotherapy group had lower recurrence
      rates than advanced FIGO stage group, non-mucinous type group, and neoadjuvant
      chemotherapy group, respectively (P=0.001, P=0.002, and P=0.025). Cox
      multivariate analysis showed that only FIGO stage was the independent risk factor
      of recurrence of ovarian cancer (risk ratio=1.771, P=0.003). There was no
      significant difference in recurrence rate between CBP and other postoperative
      chemotherapy regimen groups. More cycles of chemotherapy could not reduce the
      recurrence rate. CONCLUSION: Since FIGO stage is an independent recurrence risk
      factor of platinum-sensitive epithelial ovarian cancer patients, early diagnosis
      is the key point to decrease the recurrence rate.

PMID- 15946496
TI  - [Discovery of a new splicing type of KCHIP1 gene].
AB  - The present study aimed to find the mutations of KCHIP1 gene in breast cancer.
      KCHIP1 cDNA samples from 12 specimens of breast cancer and 12 specimens of normal
      mammary tissues were amplified by reverse transcription-polymerase chain reaction
      (RT-PCR), and directly sequenced to detect mutation. No mutation of KCHIP1 gene
      was found in these samples; while a new splicing type of KCHIP1 gene was found,
      which has an insert (162 bp) between exon 1 and exon 2 in KCHIP1 gene (AY780424).

PMID- 15946497
TI  - [Molecular genetic and epigenetic mechanisms of hepatocarcinogenesis].
AB  - Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of
      the most frequent human malignant neoplasms. Common risk factors of human HCC
      include chronic hepatitis virus (HBV and HCV) infection, dietary aflatoxin B1
      (AFB1) ingestion, chronic alcohol abuse, and cirrhosis associated with genetic
      liver diseases. Hepatocarcinogenesis is the result of interaction between
      hereditary and environmental factors. Inheritance determines individual
      susceptibility to cancer; environment determines which susceptible individuals
      express cancer. Studies of genetic and epigenetic mechanisms of
      hepatocarcinogenesis showed that HCC development is a complex polygene and
      multipathway process; the activation of proto-oncogenes and the inactivation of
      tumor suppressor genes induced by genetic and epigenetic alterations are core
      biological processes of hepatocarcinogenesis; RB1, p53, and Wnt pathways are
      commonly affected in HCCs of different etiologies, which may reflect common
      pathologic sequence of HCC: chronic liver injury, cirrhosis, atypical
      hyperplastic nodules, and HCC of early stages. Hepatitis virus infection
      associated HCCs have frequent alterations in RB1 pathway, including methylation
      of p16INK4a and RB1 genes and amplification of Cyclin D1. AFB1 exposure
      associated HCCs have frequent alterations in p53 pathway; the G-->T mutation of
      p53 gene at codon 249 has been identified as a genetic hallmark of HCC caused by
      AFB1. Alcoholism-associated HCCs have frequent alterations in both RB1 and p53
      pathways. The roles of some important genes related to cell apoptosis, DNA
      repair, drug metabolism, and tumor metastasis in hepatocarcinogenesis had been
      discussed.

PMID- 15946498
TI  - [Monitoring bcr/abl mRNA levels in imatinib mesylate treated chronic myeloid
      leukemia patients by real-time quantitative RT-PCR].
AB  - OBJECTIVE: To quantify bone marrow bcr/abl mRNA levels in imatinib mesylate
      treated Ph chromosome positive chronic myeloid leukemia (CML) patients. METHODS:
      Serial monitoring of bcr/abl mRNA levels by real-time quantitative RT-PCR
      technique (RQ-PCR) was performed in 34 cases (120 samples) of CML treated with
      imatinib mesylate. All the patients were IFNalpha based treatment failure before
      enrolled in this study and the percentage of Ph(+) bone marrow cells were over
      95%. RESULTS: The sensitivity of RQ-PCR was 10 pg RNA, with both coefficients of
      interassay and intraassay variation below 5% for standard samples. The median
      bcr/abl mRNA level of 10 patients' samples pre imatinib treatment was 5.79% with
      marked variation (0.24%-60.90%). In 72 samples post imatinib treatment, which the
      rates of Ph(+) cells [Ph(+)%] were between 0 and 94%, the mRNA level well
      correlated with Ph(+)% (r = 0.82, P < 0.001). The mRNA levels of 7 patients who
      achieved complete cytogenetic response (CCyR) within 12 months decreased
      markedly, the levels of 6 analysable patients decreased by 65.9% - 98.8% after 3
      months'treatment accordingly. The level further decreased to 0 after achieving
      CCyR. For 4 patients who achieved major cytogenetic response (Ph(+) cells < 35%)
      later than 12 months, the mRNA levels decreased slowly. The levels of 3
      analysable patients on 3 month therapy decreased by 2.5%, 18.5% and 61.6%
      compared with that before treatment. Out of 5 patients in chronic phase without
      cytogenetic response, 1 decreased, 2 increased gradually and 2 had no change. In
      4 disease progression patients, the levels increased stepwise. CONCLUSIONS:
      Serial quantifications of bcr/abl mRNA levels are necessary for imatinib treated
      patients, and are more informative than a single detection. A sharp decline of
      bcr/abl mRNA levels after the treatment implies a promise of CCyR.

PMID- 15946500
TI  - [Prognostic value of both detection of lymphoblasts in the period of early
      treatment and minimal residual disease in childhood acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: To assess the prognostic value of both morphological persistent
      disease on day 19, on complete remission (CR) and minimal residual disease (MRD)
      in the bone marrow (BM) after multiagent remission induction therapy. METHODS:
      From January 1998 to May 2003, 193 patients with newly diagnosed ALL were
      enrolled on protocol of ALL-XH-99. BM blast counts on day 19 and on CR after
      induction therapy were examined. BM MRD at the end of induction therapy was
      detected by MP-FCM. RESULTS: (1) The probability of 5-year event-free survival
      (pEFS) was significantly worse for patients with > or = 0.050 BM lymphoblasts on
      day 19 than that with < 0.050 BM lymphoblasts [(42.59 +/- 14.28)% vs (74.24 +/-
      6.67)%, P < 0.001]. (2) The 5-year pEFS was significantly worse for patients with
      a low percentage of lymphoblasts (< 0.050) in BM on CR as compared to those with
      no morphological persistent lymphoblasts [(63.47 +/- 9.23)% vs (76.41 +/- 6.09)%,
      P < 0.05]. (3) No significant difference was found in BM lymphoblasts between
      patients with MRD (> or = 10(-4) of nucleated bone marrow cells) and those
      without MRD (< 10(-4)) at the end of induction therapy (P > 0.05). The 22-month
      pEFS was significantly worse for patients with MRD as compared with those without
      MRD on CR [(23.81 +/- 20.26)% vs (94.44 +/- 5.40)%, P = 0.001]. CONCLUSIONS: BM
      lymphoblast > or = 0.050 on day 19 after induction therapy is an independent
      prognostic factor for childhood ALL; low percentage of lymphoblasts and minimal
      residual disease in BM on remission also do it. Patients with > or = 0.050
      lymphoblast in BM on day 19 or with MRD > or = 10(-4) at the end of induction
      therapy should receive altered and more intensive chemotherapy.

PMID- 15946501
TI  - [Expression of cell cycle control genes in myelodysplastic syndromes].
AB  - OBJECTIVE: To study aberrant expression of cell cycle control genes in patients
      with myelodysplastic syndromes (MDS). METHODS: Reverse transcription polymerase
      chain reaction (RT-PCR) was used to investigate the expression of cell cycle
      control genes (cyclin D2, cyclin D3, cyclin A1, cyclin E, CDK2, CDK4, CDK6, p21,
      p27, p57, Rb and E2F1) in bone marrow mononuclear cells (BMMNCs) from 29 normal
      control, 27 MDS and 19 de novo acute myeloid leukemia (AML). RESULTS: The
      expression levels of cyclin D3 (0.65 +/- 0.17, P < 0.05) and cyclin A1 (0.48 +/-
      0.04, P < 0.05) in MDS were higher than those in normal control and significantly
      lower than those in AML. The expression rates and levels of cyclin D2 (40.7% and
      0.78 +/- 0.21) and cyclin E (51.9% and 0.52 +/- 0.10) in MDS were statistically
      higher than those in normal control and AML. The expression level of CDK2 in MDS
      (0.66 +/- 0.19, P < 0.01) was higher than that in normal control (0.42 +/- 0.04)
      and the expression rate of CDK6 in MDS (25.9%) higher than in normal control
      (3.4%, P < 0.05). There was no significant difference of the expression rates and
      levels of CDK4 in MDS, AML and normal control. The expression rates and levels of
      p21 (77.8% and 1.18 +/- 0.21) and p27 (48.1% and 1.14 +/- 0.40) in MDS were
      statistically higher than those in normal control and AML. The expression level
      of p57 in MDS (0.69 +/- 0.06) was higher than that (0.53 +/- 0.05, P < 0.01) in
      normal control but lower than in AML (0.96 +/- 0.16, P < 0.01). The expression
      rate (55.6%) and level (0.85 +/- 0.17) of Rb in MDS were significantly higher
      than those in normal control and AML. The expression rate (7.4%) and level (0.39
      +/- 0.04) of E2F1 in MDS were comparable to those in normal control but lower
      than those in AML. CONCLUSION: MDS clones have aberrant mechanism of cell cycle
      control: high expressions of cyclin family members, CDK2 and CDK6 may lead to
      high proliferation; high expression of p21 and p27 may cause the G1 phase arrest.

PMID- 15946502
TI  - [Study on elimination delay in high dose methotrexate therapy in childhood acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To observe the incidence of elimination delay in high dose
      methotrexate (HDMTX) therapy, its side effects and influence to next course of
      chemotherapy and analyze the relationship between the dosage, the duration of MTX
      infusion and the morbidity of the elimination delay. METHODS: A total of 121
      childhood acute lymphoblastic leukemia (ALL) (497 infusions of HDMTX) were
      analysed in this study. The elimination delay rate and the adverse effects in
      different dose groups (3 g/m2 vs 5 g/m2) and different infusion duration groups
      (7 h vs 24 h) were compared. The adverse effect evaluation was based on the World
      Health Organization (WHO) Toxicity Grading Criteria. The rescue dosages of
      calcium folinate (CF) among these groups were compared through CF/MTX index.
      RESULTS: The overall morbidity of elimination delay was 12.1% with a relative
      risk of 30.6% for the first time. The relative risk for the second time of
      occurrence was increased to 45.9% (P < 0.01) and it was not significantly
      increased for the third time (35.3%). Children with elimination delay had lower
      platelet count (P < 0.01) and higher CF rescue dosage (P < 0.01), while the
      damage of oral mucous membrane was more severe (P < 0.05) and the next course of
      chemotherapy would be postponed for a median of 4 days in 3 g group. There was no
      significant difference in elimination delay rates between 3 g and 5 g groups
      (12.1% vs 12.0%, P > 0.05), and between 7 h and 24 h MTX infusion groups (13.6%
      vs 11.9%, P > 0.05). The only side effect occurred in 5 g group was
      gastrointestinal morbidity. The CF/MTX index of 5 g group without elimination
      delay was less than that of 3 g group (P < 0.01). CONCLUSION: Elimination delay
      in HDMTX therapy accompanies the suppression of bone marrow and damage of oral
      mucous membrane, which need more CF rescues and will postpone the following
      course of chemotherapy. Elimination delay is not associated with the duration of
      the infusion and the dosage of MTX within the range of 3 approximately 5 g/m2 but
      there are individual differences.

PMID- 15946503
TI  - [A preliminary study on the expression and biological function of recombinant
      human SCF-TPO fusion protein].
AB  - OBJECTIVE: To study the expression of recombinant human SCF-TPO fusion protein
      and its biological function. METHODS: Four primers were designed according to
      known sequences of TPO and SCF. The functional amino acid domains of TPO and SCF
      were amplified by RT-PCR from fetus hepatocytes, respectively. The expression
      plasmid pET32a/SCF-TPO was constructed by VOE gene fusion technique and expressed
      in E. coli BL21(DE3) plysS as inclusion body after isopropyl-beta-D-1
      thiogalactopyranoside (IPTG) induction. The fusion protein was tested by SDS-PAGE
      and Western blot. The biological functions of SCF-TPO fusion protein in MO7e
      cells was investigated by MTT method after purification with metal chelating
      chromatography. RESULTS: The high expression SCF-TPO fusion protein was obtained,
      reaching up to 30% of the total cellular protein. Western blot verified the
      correct fusion expression and MTT results showed the growth promoting effect of
      the SCF-TPO fusion protein on MO7e cells, with a higher promoting activity at 100
      ng/ml. CONCLUSIONS: Expressed SCF-TPO fusion protein after renaturation has
      biological activity in promoting the proliferation of MO7e cells.

PMID- 15946504
TI  - [Clonal evolution of abnormal Philadelphia chromosome-negative cells after
      imatinib mesylate therapy in patients with Philadelphia chromosome-positive
      chronic myelogenous leukemia].
AB  - OBJECTIVE: To investigate clonal evolution of abnormal Philadelphia chromosome
      negative cells (Ph- CE) after imatinib mesylate therapy in patients with
      Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML). METHODS:
      Bone marrow cells G-banding karyotype was evaluated every 3 months in 100
      patients with Ph+ CML after achieving hematologic responses on the course of
      imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated
      phase (AP) and 9 in blast phase (BP). RESULTS: After a median follow-up of 32
      months (ranged 25-34 months), 11 patients, including 5 cases in CP, 5 in AP and 1
      in BP, developed transient, interrupted or continuous Ph- CE after 3 - 29 months
      on imatinib therapy. Ph- CE emerged at the beginning of Ph+ cells decreasing or
      after Ph+ cells disappearing. The proportion of Ph- CE, was negatively correlated
      with the proportion of Ph+ cells (P < 0.05). Ph- CE commonly included +8 (45.5%)
      and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides
      Ph+ in Ph- CE. Seven of the patients with Ph- CE achieved a major cytogenetic
      response while 9 of them achieved a complete hematologic response. One patient
      with Ph- CE in AP progressed to BP 20 months after the initiation of the therapy
      while the rests remained in hematologic or cytogenetic responses. CONCLUSION: Ph-
      CE occurred in about 11% of the patients with Ph+ CML who achieved major or minor
      cytogenetic responses on imatinib therapy. After a median follow-up of more than
      2 years, most of the patients with Ph- CE were in a stable status with no disease
      progression.

PMID- 15946505
TI  - [Vascular endothelial growth factor antisense oligodeoxynucleotide enhance drug
      sensitivity of myeloid leukemia cells to homoharringtonine].
AB  - OBJECTIVE: To explore the effects of antisense phosphorothioate
      oligodeoxynucleotides (AS PS-ODN) of vascular endothelial growth factor (VEGF) on
      drug-sensitivity of AML and CML cells to homoharringtonine and its possible
      mechanism. METHODS: A7, which was the most effective AS PS-ODN selected by
      computer aid-designing and experimental assay, contains 20-mer modified with
      phosphorothioate. It was transferred into cells by lipofectin while cultured in
      2% serum medium for 8 h and then in 10% serum medium. Twenty four hours later,
      homoharringtonine was added into the culture and cultured for another 48 h. Cell
      viability was detected by trypan blue exclusion every 24 hours, cell apoptosis by
      flow cytometry, and level of VEGF protein by a VEGF ELISA kit. RESULTS: The
      combination of A7 and homoharringtonine was able to inhibit cell survival (AML
      cell survival reduced 38%, CML cell survival reduced 25%), down-regulate VEGF
      protein expression (VEGF protein expression of AML cell and CML cell declined
      25.44% and 30.81%, respectively) and increase homoharringtonine induced apoptosis
      in both AML and CML cells (apoptotic rates of AML and CML cells increased 48.29%
      and 52.76%, respectively). CONCLUSION: The VEGF AS PS-ODN is able to enhance the
      drug-sensitivity to homoharringtonine, suggesting that inner VEGF proteins in
      myeloid leukemia cells had a drug-resistant effect.

PMID- 15946506
TI  - [Clinical study of Philadelphia chromosome-positive acute lymphoblastic
      leukemia].
AB  - OBJECTIVE: To study the clinical characteristics and therapeutic outcome of Ph+
      acute lymphoblastic leukemia (ALL). METHODS: Thirty previously untreated cases of
      Ph+ B-ALL were diagnosed in our institute. The patients were treated with
      combination chemotherapy of CODP +/- L regimen, Imatinib (400 approximately 600
      mg/d) was continuously given to those who couldn't reach CR. Fourteen patients
      received allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CR,
      while 16 received consolidation of intensive chemotherapy. RESULTS: Thirty
      (32.6%) of 92 ALL patients were diagnosed as Ph+ ALL, with a median age of 25.5
      (14 - 60). Among them Ph+ as the sole anomaly was seen in 16 patients, and Ph+
      with additional chromosome abnormalities in 14. Besides the B cell markers, 23
      (76.7%) patients had CD34+ and 13 (43.3%) CD13+ and/or CD33+. Nineteen of the Ph+
      ALL patients underwent molecular analysis; 13 (68.4%) expressed P190 and 6
      (31.6%) P210. Increased WBC (> 30 x 10(9)/L) was found in 22/30 cases while WBC >
      100 x 10(9)/L in 9/30 cases. The chemotherapy complete remission rate was 68.8%
      in patients with only Ph+ versus 28.6% in those with additional chromosome
      abnormalities. All seven refractory/relapsed patients reached CR with Imatinib
      therapy. The total complete remission rate was 73.3% in all Ph+ ALL patients. The
      median remission duration was shorter in patients with additional chromosome than
      in those with only Ph+ (1 vs 7 months, P < 0.05), and so was the survival period
      (7 vs 9 months, P > 0.05). The remission duration was significantly longer in
      patients received allo-HSCT than in those received chemotherapy only (8 vs 0.5
      month, P < 0.05), and so was the survival period (12.5 vs 6 months, P < 0.05).
      CONCLUSION: Additional chromosome abnormalities negatively affect the prognosis
      and therapeutic effect of Ph+ ALL patients. Imatinib is effective for the
      induction therapy of Ph+ ALL. The survival period of patients who received allo
      HSCT was obviously longer than those who received chemotherapy only.

PMID- 15946507
TI  - [Clinical and experimental study of two cases of myelodysplastic syndromes with
      double isochromosome 20q- anomaly].
AB  - OBJECTIVE: To explore the clinical and laboratory characteristics of two
      myelodysplastic syndromes (MDS) patients with double isochromosome 20q- anomaly.
      METHODS: Bone marrow cell chromosome preparations were made with both direct
      method and short-term culture. Karyotype analysis was performed by R-banding
      technique, and dual-color FISH (fluorescence in situ hybridization) by using a
      20q telomeric probe and a sequence-specific probe for 20q12. RESULTS: The
      clinical and hematological findings were comparable with diagnosis of MDS.
      Karyotype analysis showed that both patients had double isochromosome 20q-
      anomaly: case 1 is 46, XX, der(20)? i(20q-) [6]/46, idem, der (6) i (6p) [1]/47,
      idem, +der (20)? i (20q-) [3]/47, idem, der(6)i (6p), +der(20)? i (20q-) [20];
      case 2 is 45, XY, -7, der (20)? i (20q-) [17]/46, idem, +der(20) ? i(20q-) [3].
      Two derivative chromosomes 20 were proved 20q isochromosomes with interstitial
      deletions by dual-color FISH in one patient. CONCLUSIONS: Double isochromosome
      20q- anomaly is a rare recurrent karyotype abnormality in MDS, and signals a poor
      prognosis.

PMID- 15946509
TI  - [Clonal study on single apoptotic cells in myelodysplastic syndromes].
AB  - OBJECTIVE: To investigate the clonal origin of the apoptotic hematopoietic cells
      in myelodysplastic syndromes (MDS). METHODS: Nineteen patients with MDS whose
      karyotypes had been analysed with G- or R-binding were studied. ISEL (DNA in situ
      end labelling) and FISH (fluorescence in situ hybridization) (simplified as
      ISEL/FISH) were performed simultaneously in a single nucleated cells on cytospin
      slides in 10/19 of the patients. The ratio of FISH positive cells to all
      nucleated cells and to apoptotic cells were counted. Eight slides from 4 normal
      donors induced apoptosis by Fas monoclonal antibody (McAb) were used as
      methodology control. For the rest 9 patients, different fractions of cells (PI-,
      Annexin V+PI-, Annexin V-PI-) were sorted by flow cytometry and then cytospined
      for FISH analysis (simplified as FCM/FISH). RESULTS: The mean percentage of
      abnormal clonal cells in nuclear cells in the 10 cases detected by ISEL/FISH was
      37.1%, whereas it was 24.0% in apoptotic cells. Induction by Fas McAb didn't lead
      to change of karyotype. Moreover, 8/9 patients analysed by FCM/FISH showed higher
      cell proportion with normal karyotypes in apoptosis-undergoing cells than that in
      non-apoptotic cells. CONCLUSION: Over apoptotic hematopoietic cells in MDS are
      mainly residual normal hematopoietic cells.

PMID- 15946520
TI  - [Severe hereditary coagulation factor V deficiency caused by two novel
      heterozygous mutations].
AB  - OBJECTIVE: To identify gene mutations of a pedigree with inherited factor V (FV)
      deficiency. METHODS: The activated partial thromboplastin time (APTT),
      prothrombin time (PT), FV activity (FV:C) and FV antigen (FV:Ag) tests were
      performed for phenotypic diagnosis. The genomic DNA was extracted from the
      peripheral blood of the proband and all the 25 exons and their flanks of FV gene
      were amplified by polymerase chain reaction (PCR). The PCR products were screened
      by direct sequencing and the mutations were further confirmed by restriction
      enzyme digestion. RESULTS: APTT, PT, TT, FV:C, FV:Ag of the proband were 249.2 s,
      46.6 s, 17.9 s, 0.1% and 1.5%, respectively. FII, FVII, FVIII, FIX, FX
      activities, vWF and Fg were within normal ranges. Taking the GenBank Z99572
      sequence as the reference, four mutations were identified in FV gene of the
      proband. They were a heterozygous two bases deletion in exon 13 (2238
      approximately 2239delAG) introducing a frameshift and a premature stop at codon
      689, and a heterozygous missense mutation in exon 23 (G6410T) resulting in the
      substitution of Gly for Val at codon 2079, respectively. The proband's father and
      mother were heterozygous for G6410T and for 2238 approximately 2239delAG,
      respectively. CONCLUSION: The severe FV deficiency of the proband is caused by a
      frameshift mutation of 2238 approximately 2239delAG and a missense mutation of
      G6410T, which haven't been identified before.

PMID- 15946522
TI  - [Congenital afibrinogenemia associated with a novel nonsense mutation in the FGA
      gene].
AB  - OBJECTIVE: To identify the genetic defect underlying congenital afibrinogenemia
      in a Chinese family. METHODS: Plasma fibrinogen (Fg) was assessed by both Clauss
      method and immunonephelometry. Genomic DNA was isolated from peripheral blood of
      the proband and 13 members of her family. All the exons and exon-intron
      boundaries of the three fibrinogen genes (FGA, FGB, FGG) were amplified by PCR
      followed by direct sequencing. Restriction endonuclease analysis was performed
      for the PCR products of the family members and 50 healthy donors to exclude gene
      polymorphism. RESULTS: No Fg was detected in the plasma of the proband and her
      father by Clauss method, while low levels (< 0.02 g/L) were detected by
      immunonephelometry. A homozygous C to T mutation was found in the two cases at
      nucleotide 3108 in exon 4 of FGA gene, resulting in a null mutation which encoded
      severely truncated alpha-chains owing to its premature termination at the Gln 150
      codon. The C-->T mutation eliminated a unique recognition site for restriction
      enzyme RsaI. The PCR amplified fragments of the proband and her father could not
      be digested by RsaI, showing that they are homozygous. Her mother and some family
      members are heterozygous at this site since the fragment could partly be
      digested, while the same fragment of controls could be completely digested as
      expected. CONCLUSION: The Gln (CAG)-->150stop (TAG) nonsense mutation in FGA gene
      is a novel genetic defect of congenital afibrinogenemia which, to our knowledge,
      has not been described before.

PMID- 15946523
TI  - [Fibrinogen beta chain gene mutation contributes to one congenital
      afibrinogenemia].
AB  - OBJECTIVE: To identify the fibrinogen (Fg) gene mutations in a Chinese pedigree
      of congenital afibrinogenemia. METHODS: The plasma Fg activity and protein of the
      proband and his family members were detected. Genomic DNA was isolated from the
      peripheral blood mononuclear cells. All the exons and exon-intron boundaries of
      fibrinogen gene were amplified by PCR and sequenced thereafter. RESULTS: Two
      mutations, 7972 del G in FGB and T2543A in FGG, were found in the proband.
      CONCLUSIONS: FGG2543 is a polymorphism site, which lead to the polymorphism of
      gamma144 I/K. The G deletion at base 7972 of FGB contributes to the frameshift
      mutation after amino acid 419, resulting in the truncated beta chain without the
      terminal 27 amino acids. The latter may contributes to the pathogenetic
      mechanisms in Chinese congenital afibrinogenemia patients. The G deletion at base
      7972 of FGB is identified for the first time.

PMID- 15946524
TI  - [Study on T13254C polymorphism of the platelet membrane glycoprotein VI in
      Chinese Han population].
AB  - OBJECTIVE: To investigate the T13254C polymorphism frequency in GPVI gene among
      Chinese Han population and its relevance to the arterial thrombotic diseases.
      METHODS: The enrolled population in this study consisted of 314 healthy subjects
      and 274 patients with myocardial or cerebral infarctions. GPVI T13254C genotypes
      were determined by PCR amplification of a 355 bp fragment encompassing exon 5 of
      GPVI gene, followed by Msp I digestion of the product. The digested products were
      analyzed in 15% polyacrylamide gel electrophoresis (PAGE). RESULTS: The
      frequencies of the T allele and C allele in the T13254C polymorphism were 0.9809
      and 0.0191, respectively, with a frequency of heterozygous of 0.0319, which were
      significantly different from those reported in western population (P < 0.01). As
      compared with controls, no significant difference in T13254C genotype
      distribution was found in the arterial thrombotic diseases group. CONCLUSION: The
      GPVI T13254C polymorphism appears in a low frequency in Chinese Han population.
      No relationship is found between T13254C polymorphism and the risk for thrombotic
      diseases.

PMID- 15946525
TI  - [The inherited coagulation factor XI deficiency caused by intronic mutation IVS J
      4delgttg].
AB  - OBJECTIVE: To identify gene defect in a Chinese pedigree of hereditary
      coagulation factor XI (FXI) deficiency. METHODS: The peripheral blood samples
      were collected from the proband and her family members. The plasma PT, APTT,
      FXI:C and FXI:Ag were assayed. The FXI gene exons and exon-intron boundaries of
      the proband were amplified by PCR and then sequenced directly. The mRNA of FXI in
      the peripheral blood was analyzed with RT-PCR. RESULTS: The proband and some of
      her family members had prolonged APTT. The plasma FXI:C and FXI:Ag of the
      proband, her brother and her parents were lower than 10% and 50% of the normal
      values, respectively. Nucleotide sequence analysis revealed that the proband and
      her brother had a homozygous mutation of IVS J-4delgttg in FXI gene. The mutation
      was inherited from her parents who were heterozygotes. The mutation was not found
      in 60 normal subjects. No FXI mRNA was detected in peripheral blood sample of the
      proband. CONCLUSION: The IVS J-4delgttg is a novel mutation causing FXI
      deficiency, which may interfere with mRNA splicing.

PMID- 15946526
TI  - [Study on the molecular mechanism of antithrombin gene C2759T (Leu99Phe) mutation
      causing antithrombin deficiency].
AB  - OBJECTIVE: To study the molecular mechanism of antithrombin (AT) gene C2759T
      (Leu99Phe) mutation causing AT deficiency. METHODS: A mutated AT cDNA expression
      plasmid ATM2759 was constructed by mega-primer method. ATM2759 and wild type AT
      cDNA expression plasmid ATN were transfected into COS7 cells or CHO cells by
      using Superfect reagent respectively for in vitro expression study and
      immunofluorescence assay. RESULTS: The antigen levels of AT (AT:Ag) in the cell
      lysate of ATM2759 transfected COS7 cells and the cell culture supernatant were
      174.97% and 35.63% of that of ATN transfected COS7 cells respectively, whereas
      the AT activity in the cell culture supernatant was 47.73% of the control's.
      Immunofluorescence analysis showed that the fluorescence intensity was
      significantly higher in ATM2759 transfected CHO cells than in those transfected
      with ATN. CONCLUSIONS: Leu99Phe substitution may not affect the binding capacity
      of AT with heparin. Secretion defect and intracellular accumulation of the
      mutated AT protein might be the mechanisms of this mutation causing AT
      deficiency.

PMID- 15946527
TI  - [Functions of thrombin receptors in the reversible distribution of platelet
      surface glycoprotein I balpha in activated platelets].
AB  - OBJECTIVE: To detect the redistribution of platelet surface glycoprotein (GP)Ib
      alpha and cytoskeleton reorganization in the course of thrombin receptor
      activation, and investigate the mechanism of GPIb alpha re-translocation and the
      role of thrombin receptors in platelet signal transduction. METHODS: The thrombin
      receptor activating peptide (PAR1-AP, TRAP) was used for stimulating platelet at
      different time points (0 - 60 min), then the platelet surface GPIb alpha and P
      selectin were examined with flow cytometry, and the alterations of GPIb alpha,
      actin and myosin were analyzed in cytoskeleton by Western blot and GPIb alpha
      immunoprecipitation. Cytochalasin D and/or Apyrase VII were used for
      investigating their inhibitory effect on platelet activation. RESULTS: An
      increase of P-selectin and reversible internalization of GPIb alpha were observed
      within platelets upon TRAP activation, and transient changes of actin, myosin and
      GPIb alpha/myosin, GPIb alpha/actin association were also found in this course.
      These changes were apparently blocked by cytochalasin D, which inhibited the
      incorporation of GPIb alpha, actin and myosin into cytoskeleton. Apyrase VII had
      a weak effect on GPIb alpha internalization, although it accelerated the return
      of GPIb alpha to platelet surface. In addition, Apyrase VII also quickened the
      GPIb alpha disappearance in cytoskeleton and the dissociation of GPIb/myosin or
      GPIb/actin during activation. CONCLUSION: Thrombin receptor activation takes part
      in platelet signal transduction, inducing a reversible redistribution of GPIb
      alpha. This process is related to cytoskeleton reorganisation and ADP.

PMID- 15946529
TI  - [Effect of glycoprotein alpha II bA2334C mutation on the biosynthesis and
      transportation of alpha II bbeta3 complex].
AB  - OBJECTIVE: To study the effect of glycoprotein (GP) alpha II bA2334C mutation on
      the biosynthesis and expression of alpha II bbeta3 complex. METHODS: The GP alpha
      II bA2334C eukaryotic expression plasmid pc3.1-2334M2b was constructed. Chinese
      hamster ovary (CHO) cells were transfected with the plasmid with or without
      integrin beta3 expression plasmid pc3.1-3a. The whole expression of alpha II
      bA2334C was confirmed by Western blot and the membrane expression was analyzed by
      flow cytometry. A newly constructed alpha II bA2334C GFP fusion protein
      expressing plasmid was used to determine its subcellular localization by laser
      confocal scanning microscopy. RESULTS: Expression of the mutant protein, alpha II
      bA2334C, in the transfected CHO cells was confirmed by Western blot with a lower
      rate of the mature type than the wild type control. The expression on membrane
      was only 25% of the normal. Subcellular localization analysis showed that alpha
      II bA2334C GFP was able to be expressed in CHO cells and could be transported
      from endoplasmic reticulum to Golgi apparatus. CONCLUSIONS: The mutant alpha II
      bA2334C can be synthesized in CHO cells and form alpha II bbeta3 complex.
      However, only a small fraction of the premature alpha II bA2334C can be
      transported to Golgi apparatus and transformed to mature alpha II b. The possible
      pathogenesis of this type II thrombasthenia may be that the misfolded alpha II
      bA2334C is partially degraded in the endoplasmic reticulum causing lower
      expression of alpha II bbeta3 complex on the membrane and resulting in impared
      function of platelets than normal alpha II b.

PMID- 15946530
TI  - [The dynamic analysis and the clinical significance of vascular endothelial cell
      markers and hemolysis parameters in thrombotic thrombocytopenic purpura].
AB  - OBJECTIVE: To monitor the changes of hemolysis parameters and endothelial cell
      markers in thrombotic thrombocytopenic purpura (TTP) and reveal the clinical
      significance of these changes. METHODS: vWF-cleaving protease (vWF-CP) activity
      in 3 cases of TTP was detected by Western blot. The percentages of fragmented red
      cells (FRC) were counted throughout the entire clinical course. Levels of plasma
      thrombomodulin were detected by Western blot combined with density screening in
      TTP and healthy individuals (n = 3). Concentration of plasma VEGF was measured by
      enzyme-linked immunosorbent assay in TTP and healthy individuals (n = 9). Fundus
      fluorescein angiography was performed to search the evidence of microvascular
      thrombosis in one TTP patient with impaired visual acuity. RESULTS: The lower vWF
      CP activity was observed in TTP patients; the percentages of FRC in 3 cases of
      TTP were 1.65%, 2.50%, 3.32% respectively with an average of 2.49% at the onset
      of and decreased with the improvement of the disease. The levels of plasma TM and
      VEGF were significantly elevated in TTP than those in healthy individuals, and
      related to the severity of TTP. Fundus photography in one TTP patient with
      impaired visual acuity revealed vascular occlusion in fundus arteriole and
      venulae. CONCLUSIONS: A decreased vWF-CP activity is in favour of TTP diagnosis.
      Dynamic monitoring of plasma TM and VEGF as well as percentages of FRC are useful
      indexes for reflecting the severity and evaluating therapeutic response of TTP.
      Selective fundus fluorescein angiography is useful for the judgement of
      microvascular thrombosis in TTP.

PMID- 15946531
TI  - [Study on the direct MAIPA technique in the differential diagnosis of immune and
      non-immune thrombocytopenia].
AB  - OBJECTIVE: To evaluate the clinical usefulness of direct monoclonal antibody
      immobilization of platelet antigen (MAIPA) technique in the differential
      diagnosis of immune and non-immune thrombocytopenia. METHODS: Platelet-bound
      autoantibodies in thrombocytopenic patients (immune and non-immune) were measured
      by direct MAIPA. Monoclonal antibodies against GP II b/III a, GPIb and GP I a/II
      a were used. RESULTS: The positive rates of platelet-bound GP-specific
      autoantibodies between immune (76.4%) and non-immune thrombocytopenia (3.6%) were
      significantly different (P < 0.05). The direct MAIPA had a sensitivity of 76.4%,
      a specificity of 96.4%, and a positive predictive value of 97.1% for the
      diagnosis of immune thrombocytopenia. There was a significant inverse correlation
      between platelet-bound GP II b/III a specific autoantibody levels and platelet
      counts (r = -0.338, P < 0.05). CONCLUSION: The direct MAIPA technique can be used
      to differentiate immune from non-immune thrombocytopenias.

PMID- 15946532
TI  - [The effects of chloride channel blockers on thrombocytic cytoplasmic free
      calcium concentration and platelet aggregation].
AB  - OBJECTIVE: To explore the effects of chloride channels on the regulation of
      platelet cytoplasmic free calcium concentration ([Ca2+]i) and platelet
      aggregation (PAG). METHODS: Freshly separated platelets were activated by
      thrombin. Chloride channel blockers DIDS or NFA and calcium channel blockers
      SK&F96365 or nifedipine were added to study the effects on platelet [Ca2+]i and
      PAG by a single reagent or the combination of reagents and find out the
      interactions among DIDS, NFA, SK&F96365 and nifedipine. RESULTS: Both DIDS and
      NFA could inhibit the thrombin (1 U/ml) induced PAG in a dose-dependent manner,
      whereas had little effect on resting [Ca2+]i. As compared with the control group,
      DIDS, SK&F96365 and Nifedipine could significantly reduce the PAG, Ca2+ release
      and Ca2+ influx in thrombin activated platelet (P < 0.05). The combination of
      DIDS and SK&F96365 had greater effects in reducing the PAG, Ca2+ release and Ca2+
      influx than either reagent alone (P < 0.05). The combination of DIDS and
      nifedipine also had greater effect than each alone in reducing Ca2+ release (P <
      0.05). The combination of NFA and SK&F96365 weakened each other's effect on Ca2+
      release (P < 0.05), while NFA and nifedipine weakened each other's effects on
      PAG, Ca2+ release and Ca2+ influx in thrombin activated platelet (P < 0.05).
      CONCLUSION: DIDS and NFA have no effect on the resting [Ca2+]i and the leak
      calcium influx of platelet. DIDS can inhibit the Ca2+ release, Ca2+ influx and
      PAG of platelet induced by thrombin, while NFA can only inhibit the Ca2+ release.
      The chloride channel and calcium channel blockers have interactions in affecting
      resting [Ca2+]i and PAG of platelet. The opening of chloride channel can
      influence the cellular calcium movement of platelet.

PMID- 15946533
TI  - [Study on the role of angiogenesis and related factors in leukemias].
AB  - OBJECTIVE: To observe the bone marrow angiogenesis in leukemia and evaluate the
      expression and role of endostatin (ES), vascular endothelial growth factor (VEGF)
      and its receptor (VEGFR) in leukemia patients. METHODS: Bone marrow angiogenesis
      was assayed by vWF immunohistochemical method. The ES and VEGF concentrations in
      plasma were detected by ELISA. The expression of VEGFR in leukemia cells was
      determined by flow cytometry (FCM). RESULTS: The bone marrow microvessel density
      (MVD) in 26 cases of acute leukemia (AL) [(20.78 +/- 7.75)/high-power field (HP)]
      and 5 chronic myelogenous leukemia (CML) [(28.67 +/- 7.32)/HP] at newly diagnosed
      stage was significantly higher than that in the control group [(9.29 +/-
      3.53)/HP, P < 0.01]. The bone marrow MVD in the complete remission (CR) groups,
      (11.33 +/- 5.66)/HP for AL and (17.00 +/- 8.04)/HP for CML, was significantly
      lower than that of newly diagnosed groups (P < 0.05 and < 0.01). No significant
      difference was found between the remission groups and the control group (P >
      0.05). The plasma ES and VEGF concentrations of newly diagnosed AL and CML groups
      were significantly higher than those of the control group (P < 0.05). The levels
      of plasma ES and VEGF in AL CR group and plasma ES in CML CR group decreased to
      levels comparable to normal values (P > 0.05), but the plasma VEGF in CML CR
      group was still higher than that in control (P < 0.01). AL bone marrow
      mononuclear cells had higher expression of VEGFR at various levels whereas CML
      and control samples had lower levels of VEGFR. CONCLUSIONS: Leukemia patients at
      newly diagnosed stage had remarkable angiogenesis in bone marrow and elevated
      plasma ES and VEGF concentrations. VEGFR was expressed at different levels in AL
      cells.

PMID- 15946540
TI  - [Recent advances in the study of autologous hematopoietic stem cell purging].

PMID- 15946541
TI  - [CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung
      cancer].
AB  - OBJECTIVE: To develop a novel vector system, which combines the advantages of the
      gene therapy, antiangiogenic therapy and virus therapy, and to observe its effect
      on lung cancer. METHODS: Human angiostatin gene hA(k1-5) was inserted into the
      genome of the replicative virus specific for the tumor cells by virus
      recombination technology. The expression of hA(k1-5), its effect on tumor growth
      in vitro and in vivo were studied. RESULTS: A new kind of gene-viral vector
      system, designated as CNHK200-hA(k1-5), in which the E1b55 000 gene was deleted
      but the E1a gene of adenovirus preserved, was constructed. The novel vector
      system possessed the same property as the replicative virus ONYX-015, which
      replicates in p53- tumor cells but not in normal cells, thus specifically kills
      tumor cells. In vitro, CNHK200-hA and Ad-hA both could kill A549 tumor cells but
      the latter needed 100 times more MOI to achieve the same amplitude of cell
      killing. In vivo, the therapeutic effect of CNHK200-hA on human lung cancer A549
      xenograft in nude mice was significantly better than that of Ad-hA and that of
      tumor-replicative virus ONYX-015. CONCLUSION: CNHK200-hA(k1-5), a novel vector is
      constructed in which the angiostatin gene is inserted into the genome of the
      replicative adenovirus cytotoxic to p53-negative tumor cells. It has the
      advantages of specific tumor targeting, high level gene expression in tumor
      cells, and potent tumoricidal activity.

PMID- 15946542
TI  - [Anti-tumor effect of anti-dsDNA autoantibodies].
AB  - OBJECTIVE: To investigate effects of anti-dsDNA autoantibodies on growth of tumor
      in vitro and in vivo. METHODS: BALB/c mice were inoculated with inactivated tumor
      cells and challenged s.c. with SP 2/0 and Wehi 164 tumor cells four weeks after
      the last inoculation. The naive mice were inoculated with SP 2/0 tumor cells
      immediately after incubating with sera derived from the immunized mice at week 6.
      Then the tumor size was examined. In vitro, the cytotoxicity of anti-dsDNA
      autoantibodies to tumor cells was analysed. Furthermore, apoptosis of SP 2/0 and
      Wehi 164 tumor cells induced by anti-dsDNA autoantibodies was examined by FACS.
      RESULTS: In vivo study showed that the growth of SP 2/0 and Wehi 164 tumors were
      inhibited in mice with anti-dsDNA autoantibodies, but not in mice lack of anti
      dsDNA autoantibodies. In vitro, apoptosis of SP 2/0 and Wehi 164 tumor cells was
      induced when the tumor cells were incubated with the sera containing anti-dsDNA
      autoantibodies. Statistical analysis showed that the ability of anti-dsDNA
      autoantibodies to induce apoptosis of SP 2/0 and Wehi 164 tumor cells was
      significantly correlated with affinity (r = 0.990, P < 0.01 and r = 0.901, P <
      0.05). CONCLUSION: Anti-dsDNA autoantibodies have inhibitory effect on tumor
      cells via inducing apoptosis.

PMID- 15946543
TI  - [Effect of human angiopoietin-1 on tumorigenesis and angiogenesis of gastric
      cancer].
AB  - OBJECTIVE: To investigate the role of human angiopoietin-1 (Ang1) in
      tumorigenesis and angiogenesis of human gastric cancer cell line SGC7901 in nude
      mice. METHODS: Recombinant human Ang1 sense or antisense eukaryotic expression
      vectors were constructed, and transfected by lipofectin into human gastric cancer
      line SGC7901. Stable transfectants were obtained respectively, namely 7Ang1+ for
      sense, 7Ang1- for antisense, and 7901P for empty vector transfected cells.
      Semiquantitative PCR and Western blot were employed to testify the transfection
      efficiency. Cell growth curve and cell cycle were observed by MTT assays or flow
      cytometry. In in vivo study, growth of SGC7901 xeno-transplant was observed in
      BALB/c nude mice. Microvessel density (MVD) was analyzed by immunohistochemistry
      for Factor VIII staining. RESULTS: Stably transfected cell lines were established
      and decreased expression of Ang1 protein and mRNA in the antisense transfected
      SGC7901 cells was achieved. Tumorigenesis of 7Ang1- cells on day 30 days was
      significantly inhibited with decreased MVD as compared to that in 7901P and
      7Ang1+ cells (P < 0.01). CONCLUSION: Angiopoietin-1 plays an important role in
      tumorigenesis and angiogenesis of gastric cancer which can be partially abrogated
      by antisense technique.

PMID- 15946544
TI  - [Reversal effect of haloperidol on doxorubicin resistance and chloride channel
      inhibition in erythroleukemic cell K562/Dox].
AB  - OBJECTIVE: To investigate the reversal effect of haloperidol (Hal) on doxorubicin
      (Dox) resistance and its inhibition effect on P-glycoprotein and swelling
      activated chloride channel in Dox-resistant erythro-leukemic cell line K562/Dox.
      METHODS: Tumor cell proliferation was measured by LDH assay. mRNA expressions of
      P-glycoprotein (MDR1), glutathione S-transferase Pi (GSTpi) and MDR-associated
      protein (MRP) of K562/Dox treated with Hal were assayed by RT-PCR. Chloride
      sensitive dye MQAE was loaded into K562/Dox cells and the intracellular
      fluorescence intensity was measured to evaluate the effect of Hal on chloride
      channel in swelling-activated K562/Dox cells. Coulter counter ZM and Channelyzer
      256 were used to measure cell volume regulation. RESULTS: Hal significantly
      reversed Dox resistance in K562/Dox cells after 12.50, 6.25 and 3.12 micromol/L
      Hal treatment, the chemosensitivity to Dox increased by 8.61, 4.35 and 2.25 times
      respectively. After treatment with Hal 12.50 micromol/L, MDR1 and MRP mRNA
      expression were gradually down-regulated in a time-dependent manner on d1-d3,
      reducing to 76.3% and 64.6% of the control level on d3 (P < 0.05), while GSTpi
      mRNA expression decreased by 66.1% (P < 0.05) on d1-d2, and began to recover on
      d3. The swelling-activated chloride channel and cell regulatory volume decreased
      (RVD) in K562/Dox cells were also inhibited by Hal. Under hypotonic challenge the
      cellular fluorescence intensity which represented chloride concentration declined
      by (34.46 +/- 5.91)%. After adding 6.25 micromol/L and 18.75 micromol/L Hal, the
      hypotonic challenge only caused decrease in fluorescence intensity by (24.43 +/-
      3.25)% and (16.63 +/- 4.98)% (P < 0.01). RVD in hypotonic condition was (84.95 +/
      5.69)%. RVD under hypotonic condition with 6.25 micromol/L and 18.75 micromol/L
      Hal were (51.12 +/- 6.01)% and (39.51 +/- 4.79)% respectively (P < 0.01).
      CONCLUSION: A nontoxic concentration of haloperidol can significantly reverse
      drug resistance through a multi-pathway effect, including down-regulating mRNA
      expressions of MDR, GSTpi and MRP, inhibition of swelling-activated chloride
      channel and RVD in K562/Dox cells.

PMID- 15946545
TI  - [Nuclear import of p53 in relation to MDM2-mediated degradation and
      ubiquitination].
AB  - OBJECTIVE: To study the function of p53 nuclear import in murine double minute 2
      (MDM2)-mediated ubiquitination and degradation. METHODS: Plasmid containing
      mutant p53-GFP was constructed by site-directed mutagenesis by which 5 amino scid
      residues in the nuclear localization signal (NLS) were replaced by alanine to
      produce mutant p53KRKKK-GFP. After being fused with pEGF-Nuc (NLS containing
      SV40) to produce p53KRKKK-NLS-GFP, it was transfected into U20S cells.
      Localization, degradation and ubiquitination of p53 and MDM2 proteins were
      assessed by fluorescent staining, Western blot and ubiquitination analysis in
      MDM2 or MDM2-NLS co-transfected U20S cells. RESULTS: p53KRKKK-GFP was located in
      cytoplasm, and was not degraded by either MDM2 or MDM2-NLS mutation, but could be
      ubiquitinated; p53KRKKK-NLS-GFP could be brought back to nucleus by SV-40 NLS, so
      could be both degraded and ubiquitinated by either MDM2 or MDM2-NLS; Wild type
      p53 and mutant NLS could be ubiquitinated by either wild type MDM2 or mutant NLS.
      Ubiquitination happened to be even more efficient in cytoplasm when p53KRKKK and
      MDM2-NLS co-localization, but not degraded. CONCLUSION: Nuclear import is
      required for p53 degradation mediated by MDM2, but not for ubiquitination. p53
      can be efficiently ubiquitinated in cytoplasm.

PMID- 15946546
TI  - [Telomerase RNA antisense oligonucleotides inhibit growth of human
      choriocarcinoma xenograft in nude mice].
AB  - OBJECTIVE: To study the inhibitory effect of antisense oligonucleotides against
      telomerase RNA on the growth of human choriocarcinoma transplant in nude mice.
      METHODS: Choriocarcinoma xenografts were established by transplanting JAR cells
      subcutaneously to female nude mice, and were treated with high and low doses of
      antisense oligonucleotides. Control groups were treated with NS, random sequence
      and actinomycin D (Act-D). Tumor growth was monitored once every other day.
      Telomerase relative activity was assayed by TRAP-ELISA. Western blotting was used
      to detect expression of hTERT. RESULTS: Low and high doses antisense
      oligonucleotides, and Act-D inhibited tumor growth by 76.6%, 93.8% and 85.4%
      respectively, which were significantly different when compared with random
      sequence and NS groups. Expression of telomerase relative activity and hTERT were
      decreased as well. But the differences among the first three groups had no
      significance. CONCLUSION: Telomerase RNA antisense oligonucleotide inhibits
      growth of human choriocarcinoma xenografts in nude mice. It may be a novel
      approach to the treatment of choriocarcinoma.

PMID- 15946547
TI  - [Public screening for early carcinoma of gastric cardia: rule of carcinogenetic
      development observed by endoscopy].
AB  - OBJECTIVE: To study the rule of development of early cancer of gastric cardia in
      vivo in public screening. METHODS: A prospective cohort study on gastric cardiac
      cancer was held in the high incidence area of cancer of esophagus and stomach in
      China. 106 subjects had been examined regularly by endoscopy to observe the
      change of mucosa in high incidence area of gastric cardiac carcinoma developing
      at the root of gastric cardiac ridge by taking serial biopsy specimens. All
      specimens were diagnosed through the normal pathological processes to study the
      prognosis of pre-cancerous lesion of gastric cardia. RESULTS: The result of 106
      subjects who had been observed for four years were: 1. Of 8 normal persons, 3
      stayed normal, 4 turned to chronic gastritis, 1 developed early gastric cardiac
      cancer. 2. Of 61 persons chronic gastritis, 11 was observed to have glandular
      atrophy, 4 with mild atypical hyperplasia, and 2 with highly atypical
      hyperplasia. 3. Of 9 subjects showing atrophic chronic gastritis, 5 revealed no
      change, and 4 became chronic gastritis. 4. Of 22 subjects who revealed mild
      atypical hyperplasia, 17 resolved, 4 showed no change, and 1 advanced to highly
      atypical hyperplasia. 5. One person with highly atypical hyperplasia reverted to
      mild atypical hyperplasia. 6. Of 5 subjects with early gastric cardiac cancer
      without any treatment, 1 became advanced cancer, 1 still stayed in early stage,
      and 3 turned to atypical hyperplasia. CONCLUSION: 1. The development of early
      cancer of gastric cardia would proceed through the stages of chronic gastritis,
      glandular atrophy, and atypical hyperplasia. 2. The early cancer and pre
      cancerous lesion of gastric cardia is reversible, though possessing malignant
      possibility.

PMID- 15946548
TI  - [Correlation between expression of matrix metalloproteinase-2 and angiogenesis in
      esophageal carcinoma].
AB  - OBJECTIVE: To study expression of MMP-2 in relation to microvessel density (MVD)
      in esophageal carcinoma. METHODS: Forty-eight specimens of esophageal carcinoma
      (Ec) and 17 specimens of grade II + III epithelial dysplasia (Dy) close to the
      tumor and 12 specimens of normal tissue (Nt) along the incisional margin were
      examined by S-P immunohistochemical staining with anti-MMP-2 monoclonal antibody.
      An anti-CD34 monoclonal antibody was used to show MVD. RESULTS: MMP-2 expression
      in Ec was remarkably higher than that in Dy, which was higher than that in Nt.
      MMP-2 expression in Ec and Dy was significantly correlated with MVD in the tumor
      and nearby tissue. MMP-2 expression and MVD in Ec significantly associated with
      lymph node metastasis. CONCLUSION: Expression of MMP-2 plays an important role in
      angiogenesis and lymph node metastasis of esophageal cancer.

PMID- 15946549
TI  - [Thermal dosimetric study on hyperthermia combined with radiotherapy for deep
      seated pelvic malignancies].
AB  - OBJECTIVE: To ascertain a clinically meaningful thermal dose unit-temperature
      equivalent minute (TEM) 42.5 degrees C and the relationship between TEM 42.5
      degrees C and tumor response rate. METHODS: From August 1998 to December 2002, 49
      patients with recurrent or metastatic malignancies in the pelvis were treated
      with hyperthermia combined with conventional radiotherapy. Direct thermometry
      with high resistance lead needle was used whenever possible to measure the
      temperature by inserting Teflon catheter into the tumor. TEM 42.5 degrees C was
      used as the thermal dose unit and the relationship between TEM 42.5 degrees C and
      tumor response rate was monitored. RESULTS: There was a positive correlation
      between response rate TEM 42.5 degrees C and the radiation dose. The tumor volume
      and number of heat treatment showed no influence on response. CONCLUSION: Both
      univariate analysis and multivariate logistic regression analysis indicate that
      there is a positive correlation between the response rate, TEM 42.5 degrees C and
      the radiation dose. TEM 42.5 degrees C may act as a useful thermal dose unit in
      the combination of hyperthermia and radiotherapy. To lower the incidence of
      complications in thermometry, direct thermometry with high resistance lead needle
      can be used to measure the temperature by inserting Teflon catheter into the deep
      seated malignancies.

PMID- 15946550
TI  - [Papillary renal cell carcinoma: clinico-pathologic studies of 33 cases].
AB  - OBJECTIVE: To investigate the morphologic features, differential diagnosis,
      prognosis and histogenesis of papillary renal cell carcinoma (PRCC). METHODS:
      Tumors composed of at least 50% papillae and > 1 cm in diameter were included in
      this study. Light microscopic observation, immunohistochemical assay of EMA, CK7,
      CD10, Vim, 34 beta E12 by tissue chip were performed. RESULTS: Among 516 cases of
      renal epithelial tumors 33 cases of PRCC were detected. Grossly, hemorrhage,
      necrosis and multifocality were commonly seen. Besides typical papillae,
      inconspicuous papillary patterns, such as trabecular, tubular, micronodular and
      pseudostratified patterns could be seen. Foam cells and psammoma bodies in
      stroma, and hemosiderin in tumor cells were characteristic. Tumors were of two
      major types: basophilic type (n = 10), with small cuboid cell and pale cytoplasm
      (n = 10), 9 of them were low in Fuhrman grading; eosinophilic type (n = 22) with
      large columnar cells, rich in eosinophilic cytoplasm, 19 of them were high in
      Fuhrman grading. The remaining case was of clear cell type. The basophilic tumors
      were all positive for distal tubule marker EMA/CK7, none for proximal tubule
      marker CD10, 7 tumors positive for Vim. Eosinophilic tumors were positive for
      EMA/CK7 (9/22), CD10 (10/22) and Vim (6/22). All the tumors studied were negative
      for 34 beta E12. Follow-up data were available for 24 cases (mean 37 months) with
      3-year survival rate of 64.3%, 5-year survival rate of 50%. CONCLUSION: PRCC was
      a distinct malignant entity with unique pathological features. The prognosis of
      PRCC was worse than that of chromophobe renal cell carcinoma.

PMID- 15946551
TI  - [Epitopes recognized by cytotoxic T lymphocytes in immunoglobulin heavy chain
      variable regions expressed by B-cell acute lymphoblastic leukemia].
AB  - OBJECTIVE: To clone IgHV genes from childhood B-ALL cells and identify CTL
      epitopes deduced from IgHV gene. METHODS: Seven IgHV gene families were
      respectively amplified by PCR and directly sequenced for 37 childhood B-ALL
      cases. Bioinformatics were applied for analyzing characteristics of sequences
      available and predicting HLA-A*0201 molecule-binding nonapeptides derived from
      IgHV. The predicted nonapeptide QLVQSGAEV was synthesized and its binding
      affinity to T2 cells determined. CD8+ T cells from a healthy HLA-A*0201+ donor
      peripheral blood were stimulated repeatedly with QLVQSGAEV-loaded antigen
      presenting cells. RESULTS: IgHV gene rearrangements were identified in 37 B-ALL.
      Forty IgHV gene sequences available preferentially utilized V(H)4-59 and V(H)4-34
      gene segments. Increased frequency (15.4%) of D7-27 in B-ALL IgHV was found
      compared to that reported for adult PBLs (P = 0.02); 20.0% DJ(H) junctions in B
      ALL lacked non-encoding nucleotides, a frequency higher than that reported for
      adult PBLs (P = 0.02). 17.5% B-ALL IgHV contained < 2% replacement mutations.
      Forty B-ALL IgHV sequences acquired 12 high HLA-A*0201-binding nonapeptides, 10
      (83.0%) peptides were located in frame region (FR)1 and 3. The synthesized
      peptide QLVQSGAEV up-regulated HLA-A*0201 expression 1.63 fold on the surface of
      T2 cells. The frequency of QLVQSGAEV-specific CD8+ T cells in a healthy HLA
      A*0201+ donor peripheral blood increased from 1.6% and 82.6% after two-round and
      3-round stimulations, respectively. CONCLUSION: IgHV genes in childhood B-ALL are
      of germline characteristics. Their heavy chain framework regions contain HLA
      A*0201-binding nonapeptides. These peptides are capable of inducing specific CD8+
      T cells to activate and proliferate.

PMID- 15946553
TI  - [Characteristics and prognostic factors of postoperative chemotherapy for female
      breast cancer patients under 30 years of age: a report of 129 patients].
AB  - OBJECTIVE: To analyze the clinical characteristics, survival and prognosis of
      breast cancer patients under 30 years of age. METHODS: 129 breast cancer patients
      under 30 years treated from Jan 1980 to May 2000 were retrospectively reviewed.
      Clinical features, survival and prognostic factors were analyzed by SPSS 10.0
      statistic software. RESULTS: Breast cancer patients under 30 years accounted for
      2.6% of all breast cancers in our hospital. The overall 5- and 10-year survival
      rates were 61.5% and 46.7%, respectively. For patients with tumor < or = 3 cm or
      > 3 cm, the 10-year survival rates were 65.5% and 27.4% (P < 0.01). For those
      with number of positive axillary lymph nodes 0, 1-3, or > or = 4, the 10-year
      survival rates were 79.5%, 40.9% or 31.4% (P < 0.01). For patients who had been
      treated with or without tamoxifen, the 10-year survival rates were 63.7% and 45%
      (P < 0.01). For those complicated with pregnancy and lactation which was found in
      24.8% of such patients, the 10-year survival rate was 44.3%. In the multivariate
      analysis, independent prognostic factors that might improve the overall survival
      were tumor size, axillary metastatic status and tamoxifen treatment. CONCLUSION:
      Breast cancer patients aged 30 years and younger may have good prognosis if
      multimodality treatment is given. Tumor size, axillary metastatic status and
      tamoxifen treatment are independent prognostic factors. Prognosis of patients,
      either complicated with pregnancy and lactation or not, is quite similar if the
      clinical stage is the same and if being treated by the combined therapy.

PMID- 15946554
TI  - [Anti-viral therapy using lamivudine and thymosin is helpful to prevent
      recurrence in hepatocellular carcinoma with coexisting active hepatitis B].
AB  - OBJECTIVE: To observe the effect of postoperative anti-viral therapy using
      lamivudine and thymosin alpha1 on recurrence of hepatocellular carcinoma (HCC)
      coexisting with active hepatitis B. METHODS: From Jan. 2000 to Dec. 2002, 33 HCC
      patients with coexisting with active hepatitis B were randomized into two groups:
      Group I (n = 17) received hepatectomy only, and Group II (n = 16) received
      hepatectomy and postoperative therapy using lamivudine plus thymosin alpha1. The
      suppression of HBV-DNA, HBeAg seroconversion rate, tumor recurrence rate and
      median survival in the two groups were observed and compared. RESULTS: In Group
      II and Group I, the 1-year HBV-DNA suppression rate was 100.0% vs 6.0% (P <
      0.01), HBeAg seroconversion rate was 62.5% vs 5.9% (P < 0.05), tumor recurrence
      rate was 81.3% vs 95.5% (P > 0.05), the recurrence time was 7.0 vs 5.0 months (P
      < 0.01) and median survival 10.0 vs 7.0 months (P < 0.01). CONCLUSION: Anti-viral
      therapy using lamivudine and thymosin alpha1 postoperatively may suppress the HBV
      reaction, delay the recurrence and prolong the survival for patients with HCC
      with coexisting active hepatitis B.

PMID- 15946555
TI  - [Cancer of the nasal cavity].
AB  - OBJECTIVE: To analyze the factors affecting prognosis of patients with nasal
      carcinoma. METHODS: 163 patients treated from 1985 to 1998 were analyzed. The
      survival analysis was performed by Kaplan-Meier estimate and the comparison
      between groups by Log-rank test. Multivariate analysis was carried out by Cox
      proportional hazard model. RESULTS: The overall 5-year survival rate was 58.2%.
      The 5-year survival rate was 55.8% in squamous-cell carcinoma, 44.0% in
      adenocarcinoma, 59.7% in undifferentiated carcinoma, 76.3% in adenoid cystic
      carcinoma, 71.4% in mucoepidermoid carcinoma, 25.0% in rhabdomyosarcoma, 26.7% in
      malignant melanoma, 50.0% in neuroblastoma (P > 0.05). Patients with cervical
      metastasis gave a 5-year survival of 53.5% while those without gave 58.9% (P >
      0.05). Patients with involvement of sphenoidal sinus or maxillary sinus gave the
      worse survival. The 5-year survival rate was 73.8% in patients whose cancer
      completely disappeared after treatment. It was 41.6% in patients whose cancer
      incompletely disappeared, and 34.3% in patients whose cancer remained refractory
      (P < 0.01). The 5-year survival was 78.3% in stage I disease, 56.4% in stage II
      disease, 54.2% in stage III and 35.9% in stage IV (P < 0.05). The 5-year survival
      rate of patients who were treated with radiotherapy only was 56.9%. That of
      patients who were treated with surgery only was 56.6%. That with chemotherapy
      only was 25.0% whereas that of patients treated with combination treatment was
      61.8% (P > 0.05). So far, 85 patients have died up to writing this report, 57.6%
      (49 patients) of recurrence or uncontrolled. CONCLUSION: Clinical stage,
      immediate therapeutic response and involvement of sphenoidal or maxillary sinus;
      but not the pathologic type, the presence of cervical metastasis nor the method
      of treatment, are the factors affecting the prognosis of patients with nasal
      carcinoma. Recurrence and uncontrolled disease are the cause of death.

PMID- 15946556
TI  - [Prognostic factors and treatment of 74 patients with dermatofibro-sarcoma
      protuberans].
AB  - OBJECTIVE: To analyze treatment and prognostic factors of 74 patients with
      dermatofibro-sarcoma protuberans (DFSP). METHODS: From August 1990 to November
      1999, 74 patients with DFSP confirmed pathologically were treated. There were 52
      males and 22 females with a median age of 37 years (range 4 to 80 years) on
      diagnosis. Seventeen patients were treated by extensive excision and 2 by limited
      excision. Fifty-two patients had surgical resection alone (S), and 22
      postoperative radiotherapy (S + R) of 50-70 Gy. The multivariate parameters were
      analyzed using Cox model. Kaplan-Meier and Log-Rank test were used to evaluate
      the results of the recurrence-free survival. RESULTS: The rate of recurrence was
      28.4% for all patients. The 5-year recurrence-free survival rate (RFSR) was 66.6%
      and the 10-year RFSR was 52.5%. The 5-year and 10-year in the S group were 58.4%
      and 41.2%, compared with 90.0% and 83.3% in the S + R group (P < 0.05). The 5
      year and 10-year RFSR in the pathologically positive margin group were 57.5% and
      41.4% respectively, compared with the 75.0% and 56.6% in the pathologically
      negative group (P < 0.05). Multivariate analysis suggested radiotherapy and
      negative pathological margins were favorable prognostic factors. CONCLUSION: Post
      operation radiotherapy and pathological margin are the independent prognostic
      factors.

PMID- 15946557
TI  - [Neoadjuvant chemotherapy with docetaxel plus epirubicin for locally advanced
      breast cancer: a multi-center phase II study].
AB  - OBJECTIVE: To investigate the clinical response, pathological complete response
      (pCR), tumor resection rate and safety of neoadjuvant chemotherapy with docetaxel
      and epirubicin (ET) for locally advanced breast cancer (LABC). METHODS: From
      March to December 2001, 40 women with LABC, aged from 28-67 (medium 48) years
      were alloted. Twenty patients had clinical stage IIIa disease, 15 had stage IIIb
      disease and 5 stage IV patients who had ipsilateral sura-clavicular metastasis.
      The dose was: epirubicin (E) 60 mg/m2, docetaxel (T) 75 mg/m2 every 3 weeks, with
      G-CSF given preventively. After 2 cycles of ET, a pilot clinical response
      evaluation was performed by investigators for each patient to decide if she
      should receive another 1-2 cycles of ET before surgery or radiation therapy.
      RESULTS: Thirty-eight patients received 2-3 cycles of ET regimen. The pCR,
      clinical complete response (cCR) and clinical partial response (cPR) rates were
      15.0%, 20.0% and 52.5%, respectively. Tumor resection rate in this group was
      92.5%. Incidence of III/IV Grade neutropenia was 8.4%/14.0% of cycles, and 3
      patients suffered from neutropenia with fever. Non-hematological adverse events
      were alopecia, nausea, vomiting, fluid retention, myalgia, arthralgia and nail
      disorders, which were mild to moderate. CONCLUSION: Neo-adjuvant chemotherapy
      with a combination of docetaxel and epirubicin is effective and well tolerated by
      women with locally advanced breast cancer.

PMID- 15946558
TI  - [Construction of eukaryotic expression vector of unknown KH gene and its effect
      on cell proliferation].
AB  - OBJECTIVE: To construct an eukaryotic expression vector of open reading frame of
      unknown KH gene (KH-ORF), and investigate its effect on cell proliferation.
      METHODS: The pCI-neo-KH-ORF expression vector was constructed by DNA recombinant
      technique and was introduced into COS-7 cells and K562 cells by lipofectactin
      mediated DNA transfection. Expression of KH-ORF mRNA was detected by RT-PCR. The
      effect of KH-ORF on cell cycle of COS-7 cells and K562 cells was evaluated by
      flow cytometry (FCM). Effect on cell proliferation of COS-7 cells was tested by
      MTT assay and that on K562 cells was analyzed by growth curves and LDH activity
      measurement. RESULTS: (1) KH-ORF mRNA was expressed both in COS-7 cells and K562
      cells. (2) The cell cycle and cell proliferation of COS-7 cells were unaffected
      significantly. (3) The proportion of cells in S phase was increased in pCI-neo-KH
      ORF-transfected K562 cells; and growth curves and LDH activity indicated enhanced
      cell proliferation. CONCLUSION: KH gene may be a leukemia gene related to
      proliferation of K562 cells.

PMID- 15946559
TI  - [Mutation of p53 and overexpression of STK15 in laryngeal squamous-cell
      carcinoma].
AB  - OBJECTIVE: To explore the relationship between p53 gene mutations and STK15
      abnormal expression in the development of human laryngeal squamous-cell carcinoma
      (LSCC). METHODS: LSCC tissues and matched normal tissues were taken during
      operation from 55 patients without previous chemotherapy or radiotherapy.
      Following polymerase chain reaction amplification direct sequencing single strand
      conformational polymorphism (PCR-SSCP) combined with silver staining were used to
      detect mutations of p53 gene in exons 7 and 8 (p53E7 and p53E8) using genomic DNA
      from 110 specimens including 55 LSCC tissues and 55 matched normal tissues. STK15
      expression were evaluated by RT-PCR with beta-actin as internal control. RESULTS:
      The mutation rate of p53E7 was 30.9% (compared to normal tissues, chi(2) = 8.66,
      P < 0.01). There was no mutation in p53E8. In 38 of the 55 cases (69.1%), the
      STK15 mRNA expression level was higher than that of the paired normal tissue. The
      STK15 to beta-actin ratio of average density value was 1.22 +/- 0.49 in the
      cancer tissue, and 0.99 +/- 0.54 in the normal tissues (t = 4.539, P < 0.01). In
      14 of the 17 cases (82.4%) with p53E7 mutations, the STK15 expression was higher
      than that of normal tissue. In the 38 cases with STK15 over-expression, p53E7
      mutation was found in 14 cases (36.8%). The rate of concurrence of p53E gene
      mutations and STK15 over-expression (25.5%) was higher than that of only p53E
      gene mutations (chi(2) = 26.025, P < 0.01). CONCLUSION: There is significant
      association between p53 gene mutation and STK15 over-expression in laryngeal
      squamous-cell carcinoma.

PMID- 15946560
TI  - [Screening of differentially expressed genes in mouse hepatocarcinoma ascites
      cell line with high potential of lymphatic metastasis].
AB  - OBJECTIVE: To screen genes differentially expressed in mouse hepatocarcinoma
      ascites cell line with high potential of lymphatic metastasis. METHODS: A
      subtracted cDNA library of mouse hepatocarcinoma cell line with high potential of
      lymphatic metastasis Hca-F and its synogenetic cell line Hca-P with low
      metastatic potential was constructed by suppression subtractive hybridization
      (SSH) method. The screened clones of the subtracted library were sequenced and
      GenBank homology search was performed. RESULTS: Ten differentially expressed cDNA
      fragments of Hca-F with high potential of lymphatic spreading were obtained, two
      of which were newly identified ones. CONCLUSION: SSH is a useful technique to
      detect genes of differential expression and an effective method to clone novel
      genes.

PMID- 15946561
TI  - [Effect of IL-24 gene expression on the growth of glioma cells in vitro and in
      vivo].
AB  - OBJECTIVE: To investigate the effect of IL-24 expression on the growth of glioma
      cells. METHODS: The IL-24 gene was transfected into rat glioma C6 cells with a
      retroviral vector. The expression of IL-24 in C6/IL-24 glioma cells was confirmed
      by RT-PCR. MTT assay and flow cytometry were used to study tumor cell
      proliferation in vitro. Tumorigenicity in vivo was studied in inbred SD male rats
      by the growth of intracerebrally inoculated tumor. RESULTS: It was confirmed by
      RT-PCR that the exogenous IL-24 gene expressed in C6/IL-24 cell. The C6/IL-24
      cell proliferation in vitro and tumorigenicity in vivo were both inhibited
      compared with its parental C6 cell. CONCLUSION: IL-24 expression in glioma cells
      somehow inhibits their growth in vitro and in vivo.

PMID- 15946562
TI  - [Mechanism of apoptosis induced by specific COX-2 inhibitor SC236 in gastric
      cancer cells].
AB  - OBJECTIVE: To investigate the underlying mechanism of apoptosis-inducing effect
      of a specific COX-2 inhibitor SC236 in gastric cancer cells. METHODS: Western
      blot analysis was used to measure apoptosis-related proteins, cytochrome c, and
      caspase-3. The catalytic activity of the caspases was measured using a
      colorimetric assay. RESULTS: Treatment of AGS gastric cancer cells with SC236
      caused a significant elevation of the pro-apoptotic protein Bak, release of
      cytochrome c to the cytosol, and activation of caspase-3. A specific caspase-3
      inhibitor, z-DEVD-fmk, blocked SC236-induced apoptosis. CONCLUSION: SC236
      inhibits cell growth and induces apoptosis in gastric cancer cells at least
      partly through the up-regulation of Bak, stimulation of cytochrome c release, and
      activation of caspase-3.

PMID- 15946563
TI  - [5-Aza-2'-deoxycytidine enhances differentiation and apoptosis induced by
      phenylbutyrate in Kasumi-1 cells].
AB  - OBJECTIVE: To investigate whether phenylbutyrate (PB) combined with 5-aza-2'
      deoxycytidine (5-Aza-CdR)could inhibit transcription repression and induce
      t(8;21) acute myelogenous leukemia (AML) Kasumi-1 cells to differentiate and
      undergo apoptosis. METHODS: Kasumi-1 cells were treated with PB and 5-Aza-CdR at
      different concentrations in suspension culture. Cellular proliferation was
      determined by the MTT assay, expression of myeloid-specific differentiation
      antigen and cell cycles were analyzed by flow cytometry. Cell apoptosis were
      assessed using AnnexinV/PI staining and flow cytometry. RESULTS: Treatment of
      Kasumi-1 cells with PB caused a dose-dependent inhibition of proliferation, with
      an IC(50) of 2.3 mmol/L. When combined with 5-Aza-CdR, PB resulted in a greater
      growth inhibition with an IC(50) of 1.95 mmol/L. Treatment of Kasumi-1 cells with
      PB resulted in cell cycle arrest at G(0)/G(1), while combined treatment with PB
      and 5-Aza-CdR led to cell cycle arrest at G(2)/M. Expression of myeloid cell
      differentiation antigens CD11b and CD13 induced by PB was enhanced when Kasumi-1
      cells were pretreated with low dose of 5-Aza-CdR. High, but not low,
      concentrations of 5-Aza-CdR could enhance early apoptosis of Kasumi-1 cells
      induced by PB. CONCLUSION: Phenylbuty rate, when combined with 5-Aza-CdR,
      inhibits AML cell in vitro proliferation and increases apoptosis in a synergistic
      fashion.

PMID- 15946564
TI  - [Expression of retinoic acid receptor-beta mRNA and p16, p53, Ki67 proteins in
      esophageal carcinoma and its precursor lesions].
AB  - OBJECTIVE: To study the expression of retinoic acid receptor-beta (RAR-beta) mRNA
      and p16, p53, Ki67 proteins in squamous-cell carcinoma of the esophagus and its
      precursor lesions in a high risk population. METHODS: A total of 397 tissue
      specimens were collected from individuals with normal mucosa (NM, n = 25), mild
      dysplasia (MiD, n = 69), moderate dysplasia (MoD, n = 106), severe dysplasia (SD,
      n = 51), carcinoma in situ (CIS, n = 78), and squamous-cell carcinoma (SC, n =
      68). Expression of RAR-beta mRNA was detected by in situ hybridization, and that
      of p16, p53 and Ki67 proteins by immunohistochemistry. RESULTS: The frequencies
      of RAR-beta mRNA expression in NM, MiD, MoD, SD, CIS and SC were 96.0%, 89.9%,
      67.9%, 68.6%, 62.8%, and 63.2%, respectively. The frequencies of p16 expression
      were 88.0%, 71.0%, 64.2%, 51.0%, 53.8% and 52.9%; those of p53 expression were
      4.0%, 39.1%, 57.5%, 52.9%, 67.9% and 69.1%; those of Ki67 expression were 0,
      40.6%, 61.3%, 58.8%, 59.0% and 75.0%, respectively. CONCLUSION: There are no
      significant differences in four biomarkers expression between carcinoma of the
      esophagus and its precursor lesions.

PMID- 15946565
TI  - [Expression of PKB protein in human squamous-cell carcinoma and adenocarcinoma of
      lung].
AB  - OBJECTIVE: To investigate the expression of protein kinase B (PKB) in human
      squamous cell carcinoma (SCC) and adenocarcinoma of lung (ADC) and in benign lung
      tissues (BD, lung tissues adjacent to cancer or from patients with benign lung
      diseases), and its association to clinicopathological characteristics. METHODS:
      The PKB expression in 41 specimens from patients with SCC (26 cases) and ADC (15
      cases) and in 12 specimens from patients with benign lung diseases (BD) were
      investigated by immunohistochemistry and Western blot analysis. RESULTS: PKB in
      benign lung tissues was usually weakly stained and scattered in distribution. It
      was remarkably increased in lung cancer compared to benign lung tissue. The
      positive rates of PKB in SCC and ADC were 50% (13/26), 60% (9/15), respectively,
      and there was no significant difference between them. PKB expression was
      significantly stronger in lung cancer patients in advanced stages (stage III or
      IV) or with poor differentiation, than those in early stages (stage I or II) or
      with moderate or well differentiation. The expression was stronger in patients
      with local lymph node metastasis than those without (P = 0.0391). CONCLUSION: PKB
      protein is over-expressed in human squamous-cell carcinoma and adenocarcinoma of
      lung.

PMID- 15946566
TI  - [Mediastinal lymph nodes micro-metastases in patients with clinical stage I-II
      lung cancer].
AB  - OBJECTIVE: To investigate micro-metastasis in mediastinal lymph nodes (mLN) of
      patients with clinical stage I approximately II lung cancer and its clinical
      significance. METHODS: A total of 181 mLN from 32 lung cancer patients in
      clinical stage I approximately II were collected during operation and their
      frozen sections at two different levels were examined immunohistochemically (IHC)
      with an anti-epithelial cell monoclonal antibody Ber-Ep4. Routine HE staining was
      done for comparison. The results were processed by Chi-square tests in SPSS 10.0
      soft ware. RESULTS: Fifteen of the 32 patients (46.9%) were found to have micro
      metastasis in 21 of 181 mLN (11.6%) examined by immunohistochemical staining
      though routine histopathological examinations were negative. Of those 15 cases,
      micro-metastasis was detected in 9 only by IHC and in 6 both by IHC and HE
      stainings. The positive rate of micro-metastasis in N0, N1, and N2 stratified by
      routine pathology was 36.8% (7/19), 33.3% (2/6) and 85.7% (6/7), respectively (N0
      vs N2, P < 0.05). When stratified according to clinical staging (cTNM),
      pathological staging (pTNM) and pathological staging on the basis of IHC (iTNM),
      the frequencies of N2 cases were 0, 18.8% and 46.9%, respectively (differences
      among the three groups: P < 0.01). Nine cases reported as N0(7) and N1(2) by
      routine histopathological examination were found to have micro-metastasis in mLN
      by IHC staining, therefore they were actually N2 cases. CONCLUSION: IHC staining
      with a monoclonal antibody specific for epithelial cells (Ber-Ep4) is more
      sensitive in the detection of mediastinal micro-metastais than routine HE
      staining. Underestimation of the extent of mLN metastasis by cTNM and/or pTNM
      stagings frequently exists in patients with clinically early lung cancer.

PMID- 15946567
TI  - [Correlation between expression of MMP-2, MMP-9, TIMP-2, TIMP-1 and metastasis of
      neuroblastoma].
AB  - OBJECTIVE: To study MMP-2, MMP-9, TIMP-2 and TIMP-1 expression, and their
      association to invasion and metastasis of neuroblastoma (NB). METHODS: The
      staining status was compared of MMP-2, MMP-9, TIMP-2 and TIMP-1 in cryostat
      sections of tumor tissue in 35 NB patients by immunohistochemistry. RESULTS:
      Strong expression of MMP-2 was detected only in 2 patients with early stage NB
      (group A without metastasis), but in 9 and 10 respectively with advanced stage NB
      (group B with local metastasis and group C with distant metastasis) (compared to
      group A, P < 0.01). Strong MMP-9 staining was found in 4, 8 and 11 patients for
      group A, B and C patients (group A vs group C, P < 0.05). The expression of TIMP
      2 was the strongest in 4 group A patients, but it decreased with progression of
      the disease. There was no statistical difference in TIMP-1 expression among the
      three groups of patients. CONCLUSION: MMP-2, MMP-9 expression may be related to
      metastasis and progression of neuroblastoma, while TIMP-2 may have an inhibitory
      effect.

PMID- 15946568
TI  - [Osteopontin expression and its relation to invasion and metastases in gastric
      cancer].
AB  - OBJECTIVE: To investigate the correlation between expression of the osteopontin
      (OPN) and invasion and metastases in gastric cancer. METHODS: The expression of
      OPN, NF-kappaB p65 and matrix metallo-proteinase 9 (MMP-9) was detected by
      immunohistochemistry in non-cancer gastric tissue (n = 12 cases) and gastric
      cancer tissue (n = 72 cases). RESULTS: (1) OPN, NF-kappaB p65 and MMP-9 were not
      expressed in 12 non-cancer gastric tissue samples(group A). Their expression
      rates were 43.3%, 40.0% and 46.7% respectively in 30 gastric cancer samples
      without lymph nodes metastasis (group B), but they increased to 76.9%, 73.1% and
      80.8% in 26 gastric cancer samples with lymph nodes metastases (group C), and
      87.5%, 81.3% and 93.8% respectively in 16 gastric cancer samples with lymph node
      and distant metastases (group D). (2) There were statistically significant
      differences in their expressions between group D and group B (P(a) = 0.004, P(c)
      = 0.007, P(e) = 0.002), and between group C and group B (P(b) = 0.011, P(d) =
      0.013, P(f) = 0.009). (3) Despite some differences in positive expression rates,
      correlations existed between OPN and NF-kappaB p65, and between NF-kappaB p65 and
      MMP-9 (P(1) = 0.042, P(2) = 0.013; r(1)= 0.67, r(2)= 0.72). CONCLUSION:
      Osteopondin espression is closely related to the invasion and metastases of
      gastric cancer. It may upregulate the expression of metastasis-related molecule
      MMP-9 by activating NF-kappaB pathway.

PMID- 15946570
TI  - [Comparison of primary extraovarian peritoneal serous papillary carcinoma with
      stage III-IV ovarian papillary serous carcinoma].
AB  - OBJECTIVE: Extraovarian peritoneal serous papillary carcinoma (EPSPC) is both
      histologically and clinically similar to stage III-IV ovarian papillary serous
      carcinoma (OPSC). The purpose of this study is to investigate the clinical
      findings, treatment, and outcome of EPSPC patients compared with stage III-IV
      OPSC patients. METHODS: The data of 12 EPSPC patients and 45 stage III-IV OPSC
      patients were retrospectively reviewed, comparing the characteristics on clinical
      presentation and treatment, sensitivity to first-line chemotherapy agents and
      survival. RESULTS: By analysis of patients' characteristics, presenting signs and
      symptoms, type and extent of surgery, tumor response to first-line chemotherapy,
      recurrence-free interval, recurrence site and serum CA-125 levels, no significant
      difference was observed between the EPSPC patients and stage III-IV OPSC
      controls. The prevailing presenting symptoms were abdominal mass and ascites. The
      mainstay of treatment was debulking surgery followed by adjuvant platinum-based
      chemotherapy. The complete clinical response of stage III-IV OPSC was 91.8%
      compared with 25.0% for women with EPSPC (P < 0.01). CONCLUSION: The clinical and
      surgical characteristics of EPSPC are similar to those of stage III-IV OPSC. When
      the same treatment strategy is applied, similar response and survival are
      expected in either condition.

PMID- 15946571
TI  - [Clinical characteristics and prognosis of diffuse large B-cell lymphoma].
AB  - OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell
      lymphoma (DLBCL) and the factors affecting its prognosis. METHODS: From 1994 to
      2002, 138 patients with DLBCL were confirmed by morphological and
      immunohistochemical examination. Sex, age, clinical stage, performance status
      (PS), serum lactate dehydrogenase (LDH), number of extranodal lesions, treatment
      response, cycles of chemotherapy, B symptom, erythrocyte sedimentation rate
      (ESR), 5-year survival rate and median survival time (mST) were included as the
      analysis indeces. RESULTS: Lymph nodes were involved in 87.7% of the patients,
      and extranodal lesions were found in 60.1%. Five-year survival rate was 41.3% for
      the entire group. Age, stage, PS, serum LDH, number of extranodal lesions,
      international prognostic index (IPI) and remission rates were significantly
      correlated with overall survival (OS) and mST (P < 0.05), However, sex,
      chemotherapy cycles, B symptom, ESR were not related to OS and mST (P > 0.05).
      Age, stage, remission rates were identified as independent factors affecting the
      prognosis. Combination of surgery and chemotherapy was quite impressive in the
      prolongation of survival of patients with extranodal lesions and gastrointestinal
      lymphoma compared to those by chemotherapy alone. CONCLUSION: Age, stage, PS,
      serum LDH, number of extranodal lesions, IPI, chemotherapy cycles and remission
      rates are significant factors affecting the prognosis in DLBCL patients. Age less
      than 40 years or >/= 65 years, Stage III-IV, partial remission or progressive
      disease are demonstrated as poor prognostic factors. Combined treatment is the
      strategy suggested for DLBCL patients with extranodal lesions.

PMID- 15946572
TI  - [Surgical management for pulmonary metastasis].
AB  - OBJECTIVE: To investigate the indications of resection for lung metastasis, the
      surgical procedure and factors affecting the survival based on our experience
      accumulated for 37 years. METHODS: A total of 108 patients with pulmonary
      metastasis was treated by surgery. Pathology showed 93 carcinoma (86.1%) and 15
      (13.9%) sarcoma. Totally 122 operations were performed: partial lung resection
      51, segmental lobectomy 7, lobectomy 40, pneumonectomy 15. RESULTS: After
      surgery, the cumulative 1-, 3-, 5-, 7- and 10-year post-thoracotomy survivals
      were 87.9%, 47.3%, 31.7%, 23.7% and 13.9%, with an overall median survival of
      34.8 months. Solitary lesions, disease-free interval (DFI) > 36 months, absence
      of extrathoracic disease and "open" thoracotomy were predictors of a longer
      survival whereas age, gender, symptom and pathology of the primary tumor were
      found statistically insignificant prognostic factors. CONCLUSION: Surgery should
      be undertaken for patients who do fulfill these criteria, and "open" thoracotomy
      is a better choice. Surgical treatment for patients with short DFI and multiple
      lesions should be attempted with prudence.

PMID- 15946573
TI  - [Clinical value of combined therapy with 188Re-HEDP and pamidronate in breast
      cancer with bone metastasis].
AB  - OBJECTIVE: To evaluate the clinical therapeutic value of (188)Re-HEDP combined
      with pamidronate in breast cancer with bone metastasis. METHODS: Forty-eight
      patients with breast cancer with multi-bone metastases were randomly divided into
      three groups:15 patients received (188)Re-HEDP (group A), 15 patients received
      pamidronate (group B) and 18 patients were treated by (188)Re-HEDP plus
      pamidronate (group C). RESULTS: The overall pain relief rate was 73.3%, 80.0%,
      100.0% in groups A, B and C. The response rate of bone metastasis was 40.0%,
      33.3%, 66.7% in groups A, B and C respectively. The therapeutic effect of group C
      was better than those of groups A and B (P < 0.05), without any significance in
      the difference (P > 0.05). CONCLUSION: The therapeutic effect of (188)Re-HEDP
      combined with pamidronate for breast cancer with bone metastasis is remarkable in
      bone pain relief and bone metastasis control, which is better than either (188)Re
      HEDP or pamidronate alone.

PMID- 15946574
TI  - [Hepatocellular carcinoma with tumor thrombi in the portal vein. A comparison of
      therapeutic effects by different treatments].
AB  - OBJECTIVE: To investigate the effects of different treatments for hepatocellular
      carcinoma (HCC) with tumor thrombus in the portal vein (PVTT). METHODS: From Jan.
      2000 to Jan. 2003, a total of 84 HCC patients with PVTT were divided into five
      groups based on methed of treatment: Group A (n = 9), HCC resection + PVTT
      removal + postoperative TACE + thymosin alpha(1); Group B (n = 20), HCC resection
      + PVTT removal + postoperative TACE; Group C (n = 7), HCC resection + PVTT
      removal; Group D (n = 38), TACE only; Group E (n = 10), conservative treatment
      only. RESULTS: The rate of PVTT shrinkage or disappearance of groups A, B, C, D
      and E was 66.7%, 70.0%, 57.1%, 7.9% and 0, respectively with respective median
      survival time of 10.0, 7.0, 8.0, 5.0 and 2.0 months. The one year survival rate
      was 44.4%, 15.0%, 14.3%, 10.5% and 0. CONCLUSION: Resection of HCC and removal of
      tumor thrombus in the portal vein may have the tumor thrombus cleared in most of
      the patients and postoperative TACE and thymisin alpha(1) treatment may improve
      their survival.

PMID- 15946580
TI  - Unique issues in the development of "targeted" antineoplastic pharmaceutical
      agents.

PMID- 15946581
TI  - Epidermal growth factor receptor inhibitors and their role in non-small-cell lung
      cancer.
AB  - The epidermal growth factor receptor (EGFR) is a promising target in the
      treatment of advanced stage non-small-cell lung cancer (NSCLC). Currently
      erlotinib and gefitinib are approved by the US Food and Drug Administration,
      whereas cetuximab is being studied for use in NSCLC. Erlotinib has shown a
      survival advantage in patients with advanced NSCLC. Further studies have
      identified female sex, nonsmokers, Asian race, good performance status, and
      adenocarcinoma histology as predictors of patient response to these agents. A
      genetic mutation in EGFR has also been correlated with an increase in response.

PMID- 15946582
TI  - Adjuvant therapy for resected non-small-cell lung cancer: past, present, and
      future.
AB  - Non-small-cell lung cancer has the highest mortality of all malignancies
      worldwide. Unfortunately, only the minority of patients diagnosed will have
      potentially curable disease. Over the past 30 years, dozens of trials have been
      conducted assessing adjuvant treatments to augment the survival advantage offered
      by surgery. It has only been in the past 5 years that promising results have
      begun to be seen. Cisplatin-based therapy has now been shown to provide an
      additional survival benefit in several trials and in a recent meta-analysis. The
      goal of this paper is to review the data on adjuvant therapies that have emerged
      over the past 30 years, focusing specifically on the trials that have been
      published in the past 5 years.

PMID- 15946583
TI  - Intensity modulated radiation therapy and proton radiotherapy for non-small cell
      lung cancer.
AB  - Local failure of non-small-cell lung cancer (NSCLC) radiotherapy may cause
      continuous tumor seeding and death. Radiotherapy dose escalation has been shown
      to improve local control and survival. However, the toxicities associated with
      dose escalation are significant and limit the potential of dose escalation.
      Intensity modulated radiotherapy (IMRT) may have the potential to improve the
      therapeutic ratio for photon treatment of lung cancer by sparing surrounding
      normal tissues. However, low-dose exposure to normal lung and organ motion is a
      major concern. We have conducted several studies to address these issues and
      started clinical studies to evaluate the potential benefit of IMRT in patients
      with NSCLC. Proton radiotherapy may have greater potential to spare normal tissue
      and allow for further dose escalation and acceleration. We are conducting
      preclinical and clinical studies for imaging-guided proton radiotherapy in NSCLC.
      In this paper, we discuss the preliminary data, IMRT treatment guidelines, and
      ongoing studies for proton therapy in NSCLC.

PMID- 15946585
TI  - Recombinant human erythropoietin and overall survival.

PMID- 15946584
TI  - New therapeutic options for mesothelioma.
AB  - Malignant pleural mesothelioma is an aggressive thoracic tumor that is often
      refractory to chemotherapy and radiotherapy, making long-term survival a
      difficult goal. Although multimodality therapies, including cytoreductive
      surgery, chemotherapy, and radiotherapy, have been tested, their survival benefit
      is unclear. Recently, novel cytotoxic agents such as pemetrexed have shown
      promise in the treatment of malignant pleural mesothelioma, and in early trials
      new small-molecule agents targeted to the specific biochemical properties of this
      tumor have shown promise.

PMID- 15946586
TI  - The cancer anorexia/weight loss syndrome: therapeutic challenges.
AB  - The cancer anorexia/weight loss syndrome is characterized by loss of weight, loss
      of appetite, overall decline in quality of life, and shortened survival in
      patients with advanced incurable cancer. It is highly prevalent. To date,
      treatment options that have been firmly established with good scientific evidence
      are limited to progestational agents and corticosteroids, both of which have been
      demonstrated to improve appetite but have otherwise failed to have a favorable
      impact on some of the other aspects of this syndrome. As the mechanisms behind
      this syndrome are further elucidated, more effective therapeutic strategies will
      likely emerge.

PMID- 15946587
TI  - Cancer-related fatigue: an update.
AB  - Fatigue, one of the most common symptoms experienced by cancer patients, is
      multidimensional and is associated with significant impairment in functioning and
      overall quality of life. Although the precise pathophysiology of cancer-related
      fatigue is not well understood, a number of metabolic, cytokine,
      neurophysiologic, and endocrine changes have been described in these patients. A
      better understanding of these abnormalities is likely to lead to novel
      therapeutic interventions. Clinically, all patients presenting with significant
      fatigue should be evaluated for treatable conditions that might contribute to
      this symptom. Exercise and treatment of anemia are the two most established
      interventions for cancer-related fatigue. Psychostimulants seem promising based
      on early studies. Several complementary medicine treatments that showed efficacy
      in preliminary studies merit further testing.

PMID- 15946588
TI  - Limb salvage in the skeletally immature patient.
AB  - The most common tumors of bone, osteosarcoma and Ewing sarcoma, commonly occur in
      the skeletally immature patient. Historically, amputation was the procedure of
      choice; however, improved oncologic outcome and technical advances in limb
      salvage surgery have made limb salvage therapy a feasible and valuable treatment
      option. Nevertheless, depending on the extent of the lesion within the long bone,
      it may be difficult to spare the physis, and hence, in the skeletally immature
      patient, resection of a sarcoma of bone can create a limb-length discrepancy and
      gait abnormalities. This article reviews the limb salvage options available for
      the skeletally immature patient who requires reconstruction of a segmental long
      bone defect.

PMID- 15946589
TI  - Imatinib resistance in gastrointestinal stromal tumors.
AB  - Conventional chemotherapeutic drugs are ineffective in treatment of
      gastrointestinal stromal tumors (GISTs). Imatinib (STI571, Gleevec, Glivec;
      Novartis Pharmaceuticals, East Hanover, NJ), a selective inhibitor of KIT, ABL,
      BCR-ABL, PDGFRA, and PDGFRB, represents a new paradigm of targeted cancer therapy
      and has revolutionized the treatment of patients with chronic myelogenous
      leukemia and GISTs. Unfortunately, imatinib resistance has emerged. The reported
      mechanism of imatinib resistance in GISTs involves missense mutation in the
      kinase domain of KIT, including Thr670Ile, Tyr823Asp, and Val654Ala. The
      established mechanisms and potential mechanisms of imatinib resistance in GISTs,
      the imaging studies indicative of early development of imatinib resistance, and
      the management of imatinib-resistant GISTs are discussed.

PMID- 15946590
TI  - New drug developments for patients with metastatic soft tissue sarcoma.
AB  - For the subgroup of patients with inoperable gastrointestinal stromal tumors,
      progress has been made by the rapid development and approval of the targeted
      therapy imatinib mesylate. Small round cell sarcomas (SRCT), such as
      Ewing/primitive neuroectodermal tumor, desmoplastic SRCT, and rhabdomyosarcoma,
      are chemotherapy-sensitive and potentially curable malignancies that are treated
      with multimodality dose-intensive neoadjuvant protocols regardless of size or
      overt metastatic disease. However, the number of effective cytotoxic agents for
      the treatment of patients with metastatic so-called adult soft tissue sarcoma is
      limited, especially when patients have failed anthracycline- and ifosfamide-based
      chemotherapy.

PMID- 15946592
TI  - Evaluation of the first-pass glucuronidation of selected flavones in gut by Caco
      2 monolayer model.
AB  - PURPOSE: Four flavones, namely Apigenin, Baicalein, Chrysin and Luteolin, were
      selected for study and comparison of their absorption and metabolism in gut using
      the in vitro Caco-2 monolayer model. METHODS: Transport of the four flavones in
      the Caco-2 monolayer model was studied in both Apical-to-Basolateral and
      Basolateral-to-Apical directions. RESULTS: All of the selected flavones were able
      to pass through the Caco-2 cell monolayer with no significant efflux. The
      permeability coefficients of the four compounds were all greater than 10(-6)
      cm/sec and those of Apigenin and Baicalein were even greater than 10(-5) cm/sec.
      Glucuronides of the tested flavones were all formed in the Caco-2 cell monolayer
      model and a structure-activity relationship has been proposed for this
      glucuronidation. In addition, Apical-to-Basolateral transport studies were
      performed in Caco-2 models pre-treated with Chrysin, an UGT inducer. Quantities
      of the corresponding glucuronides formed were all significantly higher in Chrysin
      treated groups than the controls. CONCLUSIONS: It demonstrated that all selected
      flavones were substrates of the UGT isoforms that are inducible by Chrysin.

PMID- 15946591
TI  - Critical issues in response evaluation on computed tomography: lessons from the
      gastrointestinal stromal tumor model.
AB  - Imaging technology plays a major role in treatment response assessment in solid
      tumors and in surveillance for recurrence or progression. Currently available
      response evaluation criteria, Response Evaluation Criteria in Solid Tumors
      (RECIST), are based on unidimensional tumor size. Recently, however, these
      strictly size-based criteria for evaluating responses have been criticized
      because they do not reflect the biologic changes of solid tumors induced by
      targeted therapies and thus may be misleading. This problem is evident in
      response evaluation in advanced gastrointestinal stromal tumor (GIST) treated
      with a new molecularly targeted agent, imatinib. GISTs can increase in size
      despite good response to imatinib, and focal progression within a responding GIST
      can be overlooked with current size-based imaging criteria. Modified objective
      criteria using a combination of tumor size and density on CT are promising in
      early response evaluation and in predicting long-term prognosis in patients with
      advanced GIST treated with imatinib. These criteria may have broad applicability
      as additional targeted therapies become available to treat solid tumors.

PMID- 15946593
TI  - Sodium citrate cross-linked chitosan films: optimization as substitute for
      human/rat/rabbit epidermal sheets.
AB  - PURPOSE. To prepare chitosan films that shall be capable of simulating in vitro
      permeation of polar (5-FU) and non polar (indomethacin) drugs across
      rat/rabbit/human epidermis. METHOD: Statistical designs were utilized to identify
      the formulation and process variables that significantly influenced permeation of
      both drugs across chitosan films cross-linked with sodium citrate (Nacit). In
      addition, atomic absorption spectroscopy for Na+ and differential scanning
      calorimetry of these films were performed for understanding the cross-linking
      behaviour. RESULTS: Concentration of chitosan, cross-linking time and
      concentration of cross-linking agent significantly influenced the in vitro flux
      of both drugs. Na+ content in films cross-linked with Nacit solutions without
      adjustment of pH was found to increase whereas, DeltaH of cross-linking
      endothermic transition decreased. However, after dipping these films in phosphate
      buffer (pH 7.4) both Na+ and DeltaH was found to decrease. Such a decrease was
      not observed when films cross-linked with sodium citrate solutions after
      adjustment to pH 5 were dipped in phosphate buffer (pH 7.4). The in vitro
      permeation of both drugs across latter films was significantly less. CONCLUSION:
      Adjustment of Nacit solution pH to 5 produced ionic complexes that were resistant
      to alkaline pH. Chitosan films can be cross-linked with Nacit to simulate in
      vitro permeation of polar and non polar drugs across animal/human epidermis.

PMID- 15946594
TI  - The effect of type and concentration of vehicles on the dissolution rate of a
      poorly soluble drug (indomethacin) from liquisolid compacts.
AB  - PURPOSE: For poorly soluble, highly permeable (Class II) drugs, such as
      indomethacin, the rate of oral absorption is often controlled by the dissolution
      rate in the gastrointestinal tract. Therefore together with the permeability, the
      solubility and dissolution behaviour of a drug are key determinants of its oral
      bioavailability. The object of the present study is to increase dissolution rate
      of indomethacin using liquisolid compacts. METHODS: Several formulations of
      liquisolid compacts containing various ratios of drug: propylene glycol (ranging
      from 1:1 to 1:4) was prepared. In this study the ratio of microcrystalline
      cellulose (carrier) to silica (coating powder material) was 20 in all
      formulations. The dissolution behaviour of indomethacin from liquisolid compacts
      and conventional formulations was investigated at different pHs (1.2 and 7.2).
      RESULTS: The results showed that liquisolid compacts demonstrated considerably
      higher drug dissolution rates than those of conventionally made capsules and
      directly compressed tablets containing indomethacin. This was due to increased
      wetting properties and surface of drug available for dissolution. Also it has
      been shown that the fraction of molecularly dispersed drug (FM) in the liquid
      medication of liquisolid systems was directly proportional to their indomethacin
      dissolution rates (DR). An attempt was made to correlate the percentage drug
      dissolved in 10-min with the solubility of indomethacin in different vehicles. A
      plot of the percentage drug dissolved against the solubility of indomethacin
      showed that the amount of drug dissolved increased linearly (correlation
      coefficient of 0.9994 and 0.996 at pH 7.2 and 1.2 respectively) with an increase
      in solubility of indomethacin in the vehicles. CONCLUSION: The liquisolid
      compacts technique can be a promising alternative for the formulation of water
      insoluble drugs, such as indomethacin into rapid release tablets.

PMID- 15946595
TI  - Formulation development, in vitro and in vivo evaluation of membrane controlled
      transdermal systems of glibenclamide.
AB  - PURPOSE: The objective of the present study was to develop the membrane
      controlled transdermal systems of glibenclamide and to evaluate with respect o
      various in vitro and in vivo parameters. METHODS: The membrane moderated
      transdermal systems were prepared using drug containing carbopol gel as reservoir
      and ethyl cellulose, Eudragit RS-100, Eudragit RL-100 and Ethylene vinyl acetate
      (EVA) (2%, 9% and 19% vinyl acetate content) rate controlling membranes. The
      possible interaction between drug and polymer was studied by IR spectroscopy, DSC
      and HPTLC analysis. The formulations were subjected to various physicochemical
      studies, in vitro drug release studies and permeation studies through mouse skin.
      The blood glucose reducing hypoglycemic activity of the systems was studied in
      both normal and diabetic mice. Various biochemical parameters and
      histopathological studies were carried out after treating the diabetic mice for 6
      weeks. Skin irritation tests, oral glucose tolerance test and pharmacokinetic
      evaluations were carried out in mice. RESULTS: The results suggested no
      interaction between drug and polymer. Variations in drug release/permeation
      profiles among the formulations containing different rate controlling membranes
      were observed. The scanning electron microscopic studies of EVA membranes
      demonstrated no changes in the surface morphology after in vitro skin permeation
      studies. The system with EVA rate controlling membrane (with 19% vinyl acetate)
      was selected for in vivo experiments. The transdermal system produced better
      improvement with respect to hypoglycemic activity, glucose tolerance test, all
      the tested biochemical, histopathological and pharmacokinetic parameters compared
      to oral administration, and exhibited negligible skin irritation. CONCLUSION: The
      present study shows that membrane controlled transdermal systems of glibenclamide
      exhibited better control of hyperglycemia and more effectively reversed the
      diabetes mellitus complications than oral glibenclamide administration in mice.

PMID- 15946596
TI  - Anti-diarrhoeal potential of Asparagus racemosus wild root extracts in laboratory
      animals.
AB  - PURPOSE: Asparagus racemosus Wild root has been used traditionally in Ayurveda
      for the treatment of diarrhoea and dysentery. However, the claims of Ayurveda
      need to be validated by a suitable experimental model. Therefore, the present
      study was undertaken to evaluate the effect of ethanol and aqueous extracts of
      Asparagus racemosus for its antidiarrhoeal potential against several experimental
      models of diarrhoea in Albino Wistar rats. METHODS: The antidiarrhoeal activity
      of ethanol and aqueous extracts of Asparagus racemosus root was evaluated using
      castor oil-induced diarrhoea model in rats. Further, we evaluated the effect of
      ethanol and aqueous extracts on gastrointestinal tract motility after charcoal
      meal administration and PGE2 induced intestinal fluid accumulation
      (enteropooling). Loperamide was used as positive control. RESULTS: The plant
      extracts showed significant (P < 0.05) inhibitor activity against castor oil
      induced diarrhoea and PGE2 induced enteropooling in rats when tested at 200
      mg/kg. Both extracts also showed significant (P < 0.001) reduction in
      gastrointestinal motility in charcoal meal test in rats. CONCLUSION: The results
      point out the possible anti-diarrhoeal effect of the plant extracts and
      substantiate the use of this herbal remedy as a non-specific treatment for
      diarrhoea in folk medicine.

PMID- 15946597
TI  - Steady-state bioequivalence study of clozapine tablet in schizophrenic patients.
AB  - PURPOSE: To compare the bioavailability of two clozapine formulations (100 mg
      Clozaril tablet from Novartis Pharmaceuticals UK Ltd., UK, as a Reference
      formulation and 100 mg Cloril tablet from Atlantic Laboratories Corp., Ltd.,
      Thailand, as a Test formulation). The present study was conducted under real-life
      conditions in schizophrenic patients using a steady-state, multiple-dose,
      randomized crossover design to avoid the risk of adverse effects in healthy
      volunteers and pharmacokinetic difference between single and multiple-dose of the
      drug. METHODS: The subjects received 100 mg bid of either the Reference
      formulation or the Test formulation for 7 days. At day-7 of each study phase,
      blood samples were collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 12 h
      after drug administration. Plasma was separated and stored at -80 degrees C until
      assay. The plasma concentration of clozapine was determined by high performance
      liquid chromatography. Pharmacokinetic parameters were calculated from the
      observed plasma-concentration time profiles. The bioequivalence between the two
      formulations was assessed by calculating individual peak plasma concentrations
      (Cmax) and area under the concentration-time curve (AUC(0-12 h)) ratios. RESULTS:
      All subjects well tolerated both clozapine formulations. No serious side effects
      were reported. The Tmax, terminal half-life and the total plasma clearance of
      clozapine (uncorrected for bioavailability) observed in the present study were
      comparable to those observed in other previous reports. All of the
      pharmacokinetic parameters investigated in the present study calculated from the
      subjects after administration of Test and Reference formulations were close. The
      90% confident interval for the ratio of means for the lnCmax (0.9784-1.0622) and
      lnAUC(0-12h) (0.9559-1.0441) are within the guideline range of bioequivalence
      (0.80 to 1.25). CONCLUSION: The result demonstrated that the Test formulation was
      bioequivalent to the Reference formulation (Clozaril) when orally administered in
      schizophrenic patients, in terms of both the rate and extent of absorption.

PMID- 15946598
TI  - Transbuccal delivery of lamotrigine across porcine buccal mucosa: in vitro
      determination of routes of buccal transport.
AB  - PURPOSE: To determine the major routes of buccal transport of lamotrigine and to
      examine the effects of pH on drug permeation. METHODS: Transbuccal permeation of
      lamotrigine across porcine buccal mucosa was studied by using in-line Franz type
      diffusion cell at 37 degrees C. The permeability of lamotrigine was determined at
      pH 4.0 to 9.0. The permeability of unionized (Pu) and ionized (Pi) species of
      drug were calculated by fitting the data to a mathematical model. Lamotrigine was
      quantified by using the HPLC method. RESULTS: The steady state flux increased
      linearly with increasing the donor concentration (r2 = 0.9639) at pH 7.4. The
      permeability coefficient and the partition coefficient of the drug increased with
      increasing the pH. The values of Pu and Pi were 0.7291 x 10(-5) cm/sec and 0.2500
      x 10(-5) cm/sec, respectively. The observed permeability coefficients and the
      permeability coefficients calculated from mathematical model at various pH showed
      good linearity (r(2) = 0.9267). The total permeability coefficient increased with
      increasing the fraction of unionized form of the drug. CONCLUSION. Lamotrigine
      permeated through buccal mucosa by a passive diffusion process. The partition
      coefficient and pH dependency of drug permeability indicated that lamotrigine was
      transported mainly via the transcellular route by a partition mechanism.

PMID- 15946599
TI  - Evaluation of the relaxant action of some Brazilian medicinal plants in isolated
      guinea-pig ileum and rat duodenum.
AB  - PURPOSE: The present study aimed to evaluate the possible antispasmodic activity
      in vitro of methanolic extracts (ME) of six Brazilian medicinal plants. METHODS:
      The extracts were evaluated on isolated guinea-pig ileum and rat duodenum
      preparations. RESULTS: Rubus imperialis, Maytenus robusta, Ipomoea pes caprae and
      Epidendrum mosenii did not inhibit the contractile response elicited by
      acetylcholine on guinea-pig ileum. On the other hand, ME from Calophyllum
      brasiliense and Cynara scolymus exhibited significant inhibitory activity for the
      contractile response elicited by acetylcholine on guinea-pig ileum and on rat
      duodenum in a noncompetitive and concentration-dependent manner. CONCLUSIONS: The
      current study suggests that, of the six medicinal plants evaluated, only the ME
      of Calophyllum brasiliense and Cynara scolymus show probable antispasmodic
      activity, confirming and justifying their use in folk medicine for the treatment
      of intestinal disorders.

PMID- 15946600
TI  - Antinociceptive effects of some synthetic delta-valerolactones.
AB  - PURPOSE: A series of delta-valerolactones has been synthesized in good yields, by
      reaction of ethyl acetoacetate with several aldehydes in presence of LDA. METHODS
      AND RESULTS: The in vivo analgesic activity of these compounds has been
      evaluated. The results indicate that the lactones synthesized showed an important
      antinociceptive effect at 10 mg/kg, administered intraperitoneally in mice, which
      significantly inhibited the abdominal constrictions induced by acetic acid when
      compared to acetylsalicylic acid and acetaminophen in the same dose, and
      increased significantly the thermal sensibility at the hot-plate method, although
      they were less effective than morphine in the same assay. CONCLUSIONS: The
      antinociceptive models employed here reveal a potential analgesic effect of the
      delta-valerolactones synthesized. Further investigations are needed to discern
      which mechanism of action is concern.

PMID- 15946601
TI  - A review of co-processed directly compressible excipients.
AB  - Direct compression is the preferred method for the preparation of tablets. The
      present review outlines the importance of the functionality of the directly
      compressible adjuvants in the formulation of tablets. The co-processing is the
      most widely explored method for the preparation of directly compressible
      adjuvants because it is cost effective and can be prepared in-house based on the
      functionality required. Hence, the present review focuses on the properties of
      the co-processed directly compressible adjuvants available in the market.

PMID- 15946602
TI  - Inhibitory effect of Gamibojungikgitang extract on mast cell-mediated allergic
      reaction in murine model.
AB  - PURPOSE: Gamibojungikgitang (GBIT) is an Oriental herbal prescription medication,
      which has been commonly used to treat allergic rhinitis in far Eastern countries
      including Korea, China, and Japan. Additionally, GBIT effectively treats ovarian
      cysts and improves ovarian functions by regulating both endocrine and metabolic
      activities. However, it has not been cleared how it prevents allergic diseases in
      experimental model. Here we report the effect of GBIT on mast cell-mediated
      allergic reactions. METHODS: The anti-anaphylactic effect of GBIT extract was
      studied against compound 48/80-induced systemic anaphylactic shock model in mice.
      Rat Peritoneal Mast Cells (RPMCs) were used to investigate the effect of GBIT
      extract on histamine release induced by compound 48/80. Passive cutaneous
      anaphylaxis activated by anti-dinitrophenyl IgE was used to know the effect of
      GBIT extract. In addition, human mast cell line HMC-1 cells culture supernatants
      that GBIT extract pretreated were assayed for IL-6 protein levels by enzyme
      linked immunosorbent assay method. RESULTS: GBIT extract dose dependently
      inhibited compound 48/80-induced systemic anaphylactic shock. When GBIT extract
      was given as pretreatment at concentrations ranging 0.01-1 mg/ml, the histamine
      release from rat peritoneal mast cells induced by compound 48/80 was reduced in a
      dose-dependent manner. GBIT extract also inhibited passive cutaneous anaphylaxis
      activated by anti-dinitrophenyl IgE. In addition, GBIT extract inhibited phorbol
      12-myristate 13-acetate + A23187-induced interleukin-6 secretion from human mast
      cell line HMC-1 cells. CONCLUSION: These results suggest a potential role for
      GBIT extract as a source of anti-anaphylactic agents for allergic disorders.

PMID- 15946603
TI  - An anti-inflammatory and anti-nociceptive effects of hydroalcoholic extract of
      Satureja khuzistanica Jamzad extract.
AB  - PURPOSE: Satureja khuzistanica Jamzad (Lamiaceae) is an endemic plant that widely
      distributed in the southern parts of Iran. This plant has been used as analgesic
      and antiseptic among the inhabitants of southern parts of Iran. METHODS: The
      Satureja khuzistanica hydroalcoholic extract was prepared and its anti
      inflammatory and anti-nociceptive effects were investigated using the carrageenan
      induced rat paw edema and formalin test. RESULTS: A similar anti-inflammatory
      activity was seen between S. khuzistanica hydroalcoholic extract (150 mg/kg;
      i.p.) and indomethacin (4 mg/kg; i.p.) in carrageenan test. The extract showed
      anti-nociceptive activity in a dose-dependent (10-150 mg/kg; i.p.) manner at the
      second phase of formalin test which was comparable with morphine (3 mg/kg; i.p.).
      CONCLUSION: This study confirms that anti-inflammatory and anti-nociceptive
      properties of S. khuzistanica are comparable to those of indomethacin and
      morphine. Presence of flavonoids, steroids, essential oil, mainly carvacrol and
      tannin might be responsible for anti-inflammatory and anti-nociceptive activities
      of this plant.

PMID- 15946604
TI  - Anti-inflammatory effects of Podophyllum hexandrum (RP-1) against
      lipopolysaccharides induced inflammation in mice.
AB  - PURPOSE: Down-regulation of lipopolysaccharide (LPS) induced hyper-inflammatory
      response by non-toxic pharmacological agents acquires paramount importance for
      countering bacterial sepsis. Anti-inflammatory potential of aqueous extract of
      Podophyllum hexandrum, a plant well documented in Ayurvedic literature for
      various therapeutic purposes, was investigated. METHODS: In vivo studies were
      performed on Balb/c mice pre-treated with supra-lethal dose of LPS endotoxin
      (E.coli 055:B5) with or without treatment with P. hexandrum extract (RP-1). Mouse
      peritoneal macrophage cultures were used to understand ex vivo effects of RP-1 on
      LPS generated nitric oxide (NO), secretion of IFN-gamma, IL-6 and TNF-alpha.
      Griess assay and sandwich ELISA method were used to quantify inducible NO and
      cytokines respectively. RESULTS: Minimal dose of LPS that rendered 100% mortality
      to mice was found to be 450 microg/kg b.w. Administration of RP-1 (200 mg/kg
      b.w., i.p.) one hour before lethal LPS treatment (0.5 mg/kg b.w.) rendered
      maximum (78%) survival. Ex vivo study revealed that RP-1 (50 microg/ml) treatment
      to peritoneal macrophages inhibited LPS (5 microg/ml) induced nitrite generation
      to 37%, IFN-gamma secretion to 5%, IL-6 secretion to 50% and TNF-alpha secretion
      to 50 % of LPS treated control values. CONCLUSION: This study has demonstrated
      anti-inflammatory potential of aqueous extract of P. hexandrum.

PMID- 15946605
TI  - Protective role of tetrahydrocurcumin (THC) an active principle of turmeric on
      chloroquine induced hepatotoxicity in rats.
AB  - PURPOSE: Tetrahydrocurcumin (THC) is an antioxidative substance, which is derived
      from curcumin, the component of turmeric. In the present investigation, the
      effect of THC and curcumin against chloroquine (CQ) induced hepatotoxicity were
      studied in female Wistar rats. METHODS: On single oral administration of CQ (970
      mg/kg body weight) the activities of serum marker enzymes namely aspartate
      transaminase, alanine transaminase and alkaline phosphatase and the levels of
      bilirubin were significantly increased with significant alterations of lipids in
      serum and lipidperoxidation markers such as thiobarbituric acid reactive
      substances (TBARS) and hydroperoxides in plasma and liver were also elevated in
      CQ treated rats. The levels of non-enzymic antioxidants (vitamin C, vitamin E and
      reduced glutathione) and enzymic antioxidants (superoxide dismutase, catalase and
      glutathione peroxidase) were also decreased in CQ treated rats. Administration of
      THC (80 mg/kg body weight) and curcumin (80 mg/kg body weight) for 8 days before
      and 7 days after single administration of CQ significantly decreased the
      activities of serum markers and lipids in serum. In addition, the level of TBARS
      and hydroperoxides were significantly decreased with significant increase in non
      enzymic and enzymic antioxidants on treatment with THC and curcumin. The
      biochemical observation was supplemented by histopathological examination of
      liver section. The results of the study reveal that THC shows more pronounced
      protective effect than curcumin against CQ induced toxicity.

PMID- 15946606
TI  - [Questions on the evaluation of areas of competence and some answers: portfolio].

PMID- 15946607
TI  - [Electronic prescription in Spain: feasibility].

PMID- 15946608
TI  - [Cost and management of asthma attacks treated in primary care (COAX Study)].
AB  - OBJECTIVES: To estimate the cost and characterize the management of asthma
      attacks in primary care. DESIGN: Prospective, observational study of 1 year's
      duration. Setting. 10 physician's offices at 9 primary care centers located in 5
      provinces (Asturias, Barcelona, Cadiz, Madrid, and Valencia) of Spain.
      PARTICIPANTS: 10 family physicians who saw 133 consecutive patients with an
      asthma attack. METHOD: Prospective, observational study; no intervention was
      used. Direct and indirect costs arising from asthma attacks were calculated.
      Episodes were treated according to the physicians' habitually used procedures;
      the study protocol did not specify any predetermined intervention. RESULTS: The
      attacks were classified as mild in 43.6% of the cases, moderately severe in
      43.6%, and severe in 12.8%. Of all severe attacks, 17.2% occurred in patients
      with intermittent asthma. The more severe the attack, the less preventive
      treatment patients had received previously. The mean cost of asthma attacks was
      166.7 (95% CI, 146.5-192.3); 80% (132.4) (95% CI, 122.7-143.8) were direct costs
      and 20% (34.3) (95% CI, 17-56.2) were indirect costs. The most economical
      management option was to change treatment, perform diagnostic tests and have the
      patient attend 2 follow-up appointments with the physician. CONCLUSIONS: Mean
      cost of each asthma attack treated in primary care was 166.7 (95% CI, 146.5
      192.3), of which 80% were direct costs and 20% indirect costs.

PMID- 15946610
TI  - [The scientific information that the pharmaceutical industry provides to family
      doctors].
AB  - OBJECTIVE: To check whether the information in the written publicity that the
      pharmaceutical industry gives to family doctors really is based on the scientific
      studies that support it. DESIGN: Cross-sectional study. SETTING: Health centre on
      the outskirts of a big city. PARTICIPANTS: Over a year, all the scientific
      studies that laboratory reps gave family doctors along with the advertising for
      medicines were collected. A total of 63 paired studies and advertising pieces
      were obtained. MAIN MEASUREMENTS: 1-3 advertising messages with each supporting
      study were selected and reviewed in a structured fashion. Then whether or not the
      messages selected were based on the study was appraised. RESULTS: 44.5% of the
      advertising messages were not based on the accompanying study; 29.9% clearly were
      based on the study; and in the rest there was a half-and-half relationship. There
      was a significant relationship between the evaluation of the advertising messages
      and the kind of study, masking and the kind of result variable. CONCLUSIONS: A
      high proportion of advertising messages are not based on the study that is
      reputed to support them. A critique of these studies has to be undertaken before
      the advertising messages can be looked at.

PMID- 15946611
TI  - [Differential pressure as an independent factor of cardiovascular risk].
AB  - OBJECTIVES: To confirm that high differential pressure (DP) supposes greater risk
      of ischaemic cardiopathy and to assess whether it is also an independent risk
      factor of suffering a cerebrovascular accident. DESIGN: An analytical,
      observational, retrospective and longitudinal study with historic cohorts.
      SETTING: Urban population of about 18 000 inhabitants. PARTICIPANTS: 300 patients
      aged between 15 and 75 with hypertension of > or =2 years evolution, who have had
      their blood pressure taken by nurses 4 or more times (excluding casualty) and
      have not suffered a cardiovascular event (CVE), whether coronary accident,
      cerebrovascular accident or peripheral vasculopathy. MAIN MEASUREMENTS: The
      history relating to cardiovascular risk was recorded: lipaemia, obesity, tobacco
      dependency, diabetes mellitus, left ventricular hypertrophy (LVH). These factors
      were considered present if their diagnosis preceded the CVE diagnosis. They were
      placed in 2 groups, depending on the degree of differential pressure: "high" if
      >60 mm Hg and "not high" if (3/4)60 mm Hg. They were analysed for intention to
      treat over 10 years, with the appearance or not of a CVE as a response variable.
      RESULTS: 300 participants (73.3% women), 150 exposed to risk and 150 not exposed.
      The initial analysis showed significant differences between the 2 groups for age
      (P<.0001), diabetes (P<.0001), and LVH (P<.001). After logistic regression, the
      OR of suffering LVH was 2.38 (95% CI, 1.19-4.74) in the group with high DP; the
      OR of ischaemic cardiopathy, 2.84 (95% CI, 1.16-6.96); and of cerebrovascular
      accident, 2.70 (95% CI, 1.09-6.68). There were no significant differences for
      peripheral arteriopathy. CONCLUSIONS: DP was confirmed as an independent factor
      of cardiovascular risk and, despite the limitations of the study, it was pointed
      to as a possible independent factor of cerebrovascular risk.

PMID- 15946612
TI  - [What are users views of medical residents attending primary care
      consultations?].
AB  - OBJECTIVE: To find what users think of the presence of medical residents (MIR) at
      primary care consultations. DESIGN: Observational and cross-sectional descriptive
      study. SETTING: Urban health centre. PATIENTS: 421 patients, selected by
      systematic sampling, attending consultations of MIR tutors. METHOD: A structured
      questionnaire was drawn up, with some closed questions with multiple-option
      replies on the Likert scale; and others with a yes/no or "indifferent" reply. The
      questionnaires were filled out in the waiting-rooms. RESULTS: 100% (63% women,
      37% men) answered the questionnaire. 71% preferred to be seen by the same doctor;
      and 68% thought they were better treated if they were always seen by the same
      doctor. 89% thought that the presence of the resident was a necessary part of
      his/her training; 90% were not bothered by his/her presence during the
      consultation; 82% thought the resident did not obstruct in any way their
      relationship with the doctor; 94% thought that the presence of the resident had
      never stopped them mentioning something important; 55% thought that patients had
      the right to an opinion on the presence of the resident. CONCLUSIONS: Most
      patients valued the presence of residents at consultations positively and thought
      it a necessary part of their training.

PMID- 15946613
TI  - [Primary prevention with statins, consensus and risk tables].

PMID- 15946614
TI  - [Effectiveness of a recuperative primary care intervention in patients with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVES: The main objective is to assess the effect of a respiratory
      rehabilitation programme on the quality of life of patients with COPD. Secondary
      aims are to determine whether the intervention, as against the habitual
      monitoring, improves tolerance to exercise and pulmonary function, and reduces
      dyspnoea, the number of crises and hospital admissions due to COPD and the
      medication used to control the disease. DESIGN: Pragmatic cluster-randomised
      clinical trial. SETTING: Clinics of 16 PC teams in various health areas of the
      Community of Madrid. PARTICIPANTS: 476 patients with light-moderate COPD, who
      sign their informed consent. VARIABLES: Quality of life, number of crises,
      packages of medicines used to control the disease, unscheduled attendance,
      pulmonary function, dyspnoea and tolerance to exercise. METHOD: The consultations
      will be assigned to the control and intervention groups at random. At each clinic
      there will be a randomised selection from all patients with COPD and in a stable
      clinical condition. 238 patients are needed in each group, in order to detect a
      minimum difference of 4 points in quality of life, assuming a standard deviation
      of 16, 95% confidence level, 80% power and 20% losses. The effect between each
      factor and the variables evaluated through multivariate analysis will be
      calculated. DISCUSSION: This research project aims to show that a basic
      recuperative intervention, which is feasible and primary care-based, can achieve
      improvements in the quality of life of patients with COPD.

PMID- 15946615
TI  - [Counselling our patients to stop smoking: why,when, and how?].

PMID- 15946616
TI  - [Use of topical tacrolimus and its side-effects].

PMID- 15946617
TI  - [Health and the communications media].

PMID- 15946618
TI  - [What impact did the papers at the last atencion primaria congress in castilla-la
      mancha have?].

PMID- 15946619
TI  - [Diagnosing metabolic syndrome in primary care,too: Basal glucemia and
      glycosylated haemoglobin may not be sufficient].

PMID- 15946620
TI  - [Health costs in primary care: as well as Cinderella, the ugly duckling].

PMID- 15946621
TI  - [Use of COX-2 Inhibitors].

PMID- 15946622
TI  - Protocol-driven allergy.

PMID- 15946623
TI  - Comparison of the allergenic potency of spores and mycelium of Cladosporium.
AB  - The allergenic potency of spore and mycelium extracts of Cladosporium was
      estimated by RAST, RAST inhibition and PCA tests. Spores contained a
      concentration of allergens higher than mycelia. Results of PCA tests suggested
      that spores contained specific allergens. However, in a comparative study of
      extracts from different species of Cladosporium animal and human models gave
      different estimates of the allergenic potency of the different species. In spite
      of these variations it was shown that extracts from spores of Cladosporium
      contained the highest amount of Cladosporium allergens.

PMID- 15946624
TI  - [Interleukin levels in umbilical cord blood: relationship with a family history
      of allergic disease].
AB  - BACKGROUND: The development of allergic pathology takes place as result of an
      alteration of the immunity and alteration of the corporal mechanism of
      protection, giving rise to an erroneous answer or exaggerated forehead to
      innocuous antigens, that it generates clinical symptoms with cutaneous, digestive
      or respiratory manifestations. The frequency and distribution of this process
      have undergone an increase from the 1970, which causes that a greater interest in
      the knowledge of the mechanisms exists that produce this clinic. The answer by
      immunoglobulin E is regulated by the answer of lymphocytes T-helper-1 represented
      by interleukin 2 and gamma-interferon that inhibits their production, and the
      answer of lymphocytes T-helper-2 formed by interleukin 4, interleukin 10 and
      interleukin 13 that stimulate the production of immunoglobulin E. METHODS AND
      RESULTS: A study of cases and controls with a sample of 70 appears new born
      considering antecedent relatives of first degree of allergic disease (47 no, 23
      yes). Values in umbilical cord blood were moderate of interleukins 4, 10, 13 and
      gamma-interferon (kit CLB, and method ELISA). Values for interleukin 4 and
      interleukin 13 have not been obtained. One has been greater values of interleukin
      10 in children of mother or brother affection (mother affects IL 10 = 48.7 pg/ml,
      in front of mother does not affect IL 10 = 31.62 pg/ml, p = 0.081, no
      signification), (brother affection IL 10 = 72.8 pg/ml, in front of brother no
      affection IL 10 = 32.31 pg/ml, p = 0.0062, is significant). Difference for gamma
      interferon was not obtained. CONCLUSIONS: As it has already been shown in other
      studies, interleukin 10 increases in cord blood in children whose mother is the
      one who presents the disease. It emphasizes the increase of interleukin 10 in
      blood of umbilical cord of children with brother affection of allergic disease.
      Still it is left much to do and by means of later pursuit it is hoped to obtain
      interest results.

PMID- 15946625
TI  - Evaluation of paediatric tolerance to an extract of Alternaria alternata under
      two treatment regimes. A multicentre study.
AB  - In order to evaluate the efficacy and safety of an extract of Alternaria
      alternata in a paediatric population, a two phase study plan has been elaborated
      that in the first place consists of a retrospective analysis of tolerance under
      the standard treatment regimes used by the clinical groups involved. This was
      achieved by analysing the records of 94 patients that have been treated with this
      extract, these being consecutive patients included at 7 clinics over a period of
      6 months. Two regimes were used: a conventional short regime of 7 doses and a
      cluster regime. Under neither of these two regimes were any serious reactions
      registered. The percentage of local reactions was significantly greater using the
      short conventional regime than with the cluster regime (1.9% and 0.4%
      respectively, p = .035). In contrast, no significant differences were observed
      with respect to the systemic reactions (0.5% and 1.2%), these percentages also
      being similar to those registered with other extracts in which identical regimes
      have been used. In conclusion, we can confirm that a very satisfactory tolerance
      profile was observed, with the advantage that through using shorter regimes than
      the conventional regime of 13 doses, a considerable saving is made both in the
      number of visits and the doses necessary to reach the maintenance dose.

PMID- 15946626
TI  - Safety and tolerability of ultra-Rush (20 minutes) sublingual immunotherapy in
      patients with allergic rhinitis and/or asthma.
AB  - BACKGROUND: The safety and good tolerability of sublingual immunotherapy (SLIT)
      has already been proved in allergic patients, but only one study has investigated
      the occurrence of immediate adverse reactions in allergic patients after a 2-hour
      ultra-rush regimen of SLIT performed with a chemically modified extract
      (sublingual monomeric allergoid, Lais, Lofarma S.p.A., Milan). The objective of
      the present study was to evaluate the occurrence of immediate adverse reactions
      in allergic patients after a very fast (20 minutes) ultra-rush regimen of
      sublingual allergoid SLIT. METHODS AND RESULTS: We studied 105 patients: 28
      children (20 male, mean age 13.3 +/- 2.1 yr) and 77 adults (29 male, mean age
      34.7 +/- 9.9 years) with a history of intermittent/persistent rhinitis or
      intermittent/mild persistent asthma due to House Dust Mite (n = 56), Parietaria
      (n = 34) and Timothy-grass (n = 15) The build-up ultra-rush phase involved the
      administration, every five minutes, of increasing doses of the sublingual
      allergoid SLIT. All patients tolerated the treatment very well. Only one patient
      out of 105 (0.9%) had a mild local symptom (gastric pirosis) that occurred 30
      minutes after the last initial dose and spontaneously disappeared as the
      treatment was continued. CONCLUSIONS: These data show the excellent safety and
      tolerability profile of an ultra-rush SLIT regimen performed with a chemically
      modified extract, even when high doses were administered through an extremely
      short induction phase (20 minutes), thus confirming the previously reported
      results.

PMID- 15946627
TI  - [Sensitization to Castanea sativa pollen and pollinosis in northern Extremadura
      (Spain)].
AB  - BACKGROUND: Castanea sativa pollen allergy has generally been considered to be
      uncommon and clinically insignificant. In our geographical area (Plasencia,
      Caceres, Spain) Castanea sativa pollen is a major pollen. OBJECTIVE: To determine
      the atmospheric fluctuations and prevalence of patients sensitized to Castanea
      pollen in our region and to compare this sensitization with sensitizations to
      other pollens. METHODS: Patients with respiratory symptoms attending our
      outpatient clinic for the first time in 2003 were studied. The patients underwent
      skin prick tests with commercial extracts of a battery of inhalants including
      Castanea sativa pollen. Serologic specific IgE to Castanea sativa pollen was
      determined using the CAP system (Pharmacia and Upjohn, Uppsala, Sweden). Airborne
      pollen counts in our city were obtained using Cour collection apparatus over a 4
      year period (2000 to 2003). RESULTS: The most predominant pollens detected were
      (mean of the maximal weekly concentrations over 4 years in pollen grains/m3):
      Quercus 968, Poacea 660, Olea 325, Platanus 229, Pinus 126, Cupresaceae 117,
      Plantago 109, Alnus 41, Populus 40, Castanea 32. We studied 346 patients (mean
      age: 24.1 years). In 210 patients with a diagnosis of pollinosis, the percentages
      of sensitization were: Dactylis glomerata 80.4%, Olea europea 71.9%, Fraxinus
      excelsior 68%, Plantago lanceolata 62.8%, Chenopodium album 60.9%, Robinia
      pseudoacacia 49%, Artemisia vulgaris 43.8%, Platanus acerifolia 36.6%, Parietaria
      judaica 36.1%, Populus nigra 32.3%, Betula alba 27.6%, Quercus ilex 21.4%, Alnus
      glutinosa 20.9%, Cupressus arizonica 7.6% and Castanea sativa 7.1%. Fifteen
      patients were sensitized to Castanea sativa and 14 had seasonal
      rhinoconjunctivitis and asthma. Ten patients had serum specific IgE to Castanea
      pollen (maximum value: 17.4 Ku/l). Castanea pollen is present in our area in
      large amounts from the 23rd to the 28th weeks of the year, with a peak pollen
      count in the 25th week. CONCLUSIONS: The most important allergenic pollens in
      northern Extremadura were Poaceae, Olea europaea and Plantago sp. The prevalence
      of sensitization to Castanea sativa pollen was very low (7.1%). Most sensitized
      patients had asthma and polysensitization. Castanea sativa pollen is not a major
      cause of pollinosis in our area.

PMID- 15946628
TI  - The prevalence of allergic rhinitis in urban and rural areas of Eskisehir-Turkey.
AB  - Allergic rhinitis is the most common allergic disease in our country. The
      epidemiology of allergic rhinitis varies according to the geographic regions of
      the country. The aim of this study was to find out if it also differs in urban
      and rural areas of the same region. The study groups were randomly selected in
      order to sample high school students living in small towns or villages in rural
      areas and in the city center. Initially the screening questionnaires about
      allergic rhinitis were responded by the students at school. Then the
      questionnaires were evaluated. Seven hundred eighty-three students who had a
      positive questionnaire outcome were underwent an ENT examination. Then skin tests
      and blood analysis were performed to two hundred forty-six students who were
      diagnosed as allergic rhinitis clinically. Prick test results was found to be
      positive 61.8% in urban areas and 46.7% in rural areas. The comparison of the
      ratios of urban and rural areas was significant. Similar results were obtained in
      serum specific Ig E analysis. The correlation of specific Ig E levels and skin
      prick test results was significant in all allergens. Allergic rhinitis is a
      medical and economic problem all over the world and further epidemiologic
      investigations should be performed.

PMID- 15946629
TI  - [Directory of diagnostic tests in primary immunodeficiencies].
AB  - The clinical and immunological characteristics that suggest diverse forms of
      primary immunodeficiency are discussed. Data on the hospitals that perform
      immunological, molecular and genetic tests for the diagnosis of most of the
      primary immunodeficiencies in Spain are presented.

PMID- 15946630
TI  - [Treatment strategies in rhinoconjunctivitis and asthma during pregnancy].
AB  - BACKGROUND: The incidence of asthma is high, especially in young people, a
      population group that includes women of reproductive age. We reviewed recent
      publications on asthma control during pregnancy to avoid undesired effects on
      both the mother and fetus. The prevalence of rhinoconjunctivitis is also high,
      although this disease is often under-treated by physicians. The use of beta2
      agonists, corticoids (systemic/inhaled/nebulized), epinephrine and specific
      allergen immunotherapy is discussed. METHODS: We reviewed recent publications on
      asthma during pregnancy as well as other articles of interest. Articles providing
      data on drug therapy, overall strategies and patient education were selected.
      Sufficient drugs are available for the management of this disease and under
      treatment cannot be justified. CONCLUSIONS: Pregnancy is not a disease, but
      constitutes a period when special care must be taken with underlying diseases.
      The aim of asthma treatment during pregnancy is to prevent fetal complications
      due to the effects of medication and asthma crises by keeping the mother symptom
      free and preventing possible exacerbations. Almost all authors agree that asthma
      crises in pregnant women should be treated no differently from those in non
      pregnant women. Treatment of rhinoconjunctivitis should not be stopped during
      pregnancy since a wide variety of FDA category B drugs is available. Specific
      allergen immunotherapy should not be suspended during pregnancy as it is not
      contraindicated. However, this therapy should not be initiated during pregnancy.

PMID- 15946631
TI  - [Recurrent angioedema and hypereosinophilia].
AB  - INTRODUCTION: Among the various causes of eosinophilia are the syndrome first
      described by Gleich in 1984. This syndrome is characterized by angioedema of the
      face, neck, extremities and trunk, weight gain, hypereosinophilia (60-70%),
      fever, and increased serum IgM levels without involvement of the vital organs.
      CASE REPORT: A 17-year-old non-allergic woman was referred to our hospital for
      further investigation of recurrent angioedema, initially of the hands and feet
      and subsequently of the face, with onset 3 years previously. The attacks had
      become more frequent and severe and had occurred monthly in the previous year.
      The patient also showed general malaise, without fever. Complementary
      investigations revealed eosinophils 40.8%, total count 3,300/mm3, and serum IgM
      levels 343 mg/dl (normal range: 53-300 mg/dl). Possible causes of
      hypereosinophilia and eosinophilic infiltration of vital organs were ruled out.
      The patient was treated with oral corticosteroids which produced clinical
      remission and reduction of eosinophil count (1.7%, total 200/mm3). DISCUSSION:
      Gleich syndrome is uncommon and has well-defined clinical features and a benign
      course. We describe a patient who presented the clinical characteristics of this
      syndrome with good response to steroids and without involvement of vital organs.
      CONCLUSIONS: Our patient presented clinical features compatible with a diagnosis
      of Gleich syndrome. Other entities associated with hypereosinophilia were ruled
      out.

PMID- 15946632
TI  - Cold urticaria associated with acute serologic toxoplasmosis.
AB  - Cold urticaria is defined as a urticarial and/or angioedematous reaction of the
      skin to contact with cold objects, water or air. Types of urticaria associated
      with infectious diseases, such as mononucleosis, rubeola, varicella, syphilis,
      hepatitis, and HIV infection have been reported. We present the case of a patient
      who developed cold urticaria associated with acute serologic toxoplasmosis. The
      patient was a 34-year-old man who for the previous 2 months had presented
      cutaneous pruritus accompanied by several papular lesions in parts of the skin
      exposed to cold as well as those in contact with cold water. The result of an
      "ice-cube test" was positive. Serologic tests for Toxoplasma gondii showed an IgG
      level of 68 UI/ml and were positive for IgM, while a test for cryoglobulins was
      positive. One month later cryoglobulins were negative and a serologic test for T.
      gondii showed an IgG concentration of 75 UI/ml and positive IgM. Three months
      later cryoglobulins were still negative, IgG for T. gondii was 84 UI/ml, and IgM
      was positive. After 6 months cryoglobulins were still negative, IgG level was 68
      UI/ml and IgM was still slightly positive. In the final evaluation, 14 months
      later, IgG level was 32 UI/ml and IgM was negative. The patient continues to
      present clinical manifestations of cold urticaria, although he has experienced
      some improvement and his tolerance to cold has increased after treatment with
      cetirizine.

PMID- 15946634
TI  - Effects of 2,2'4,4'5,5'-hexachlorobiphenyl (PCB 153) on plasma sex steroids and
      vitellogenin in rockfish (Sebastes schlegeli).
AB  - We examined the estrogenic effect of 2,2'4,4'5,5'-hexachlorobiphenyl (PCB 153) on
      the rockfish, Sebastes schlegeli. We measured levels of plasma estradiol-17beta
      (E(2)) and testosterone (T) by radioimmunoassay (RIA). Plasma concentrations of T
      and 17alpha-hydroxyprogesterone in female and male fish injected with PCB 153
      using two dosages (0.16 mg/kg body weight. and 0.57 mg/kg) did not differ
      significantly between sexes or from sham-injected controls of the same sex.
      Plasma concentrations of E(2) in females injected with PCB 153 (both levels)
      increased at 12 and 24 h. Concentrations of plasma vitellogenin (VTG) in females
      increased 72 h after injection with PCB 153 and reached 0.38 and 1.25 mg/mL,
      respectively. No VTG was detected in males injected with the same dosage. These
      results suggest that PCB 153 may lead to the production VTG in female rockfish
      through a synergistic effect with E(2), resulting in indirect disruption of the
      aromatization process.

PMID- 15946633
TI  - Pancreatitis due to codeine.
AB  - Pancreatitis is a rare adverse effect of codeine. We report the case of a 42-year
      old man who suffered from epigastric pain 1 hour after taking a tablet containing
      amoxicillin plus clavulanic acid (500/125 mg) and another tablet containing
      acetaminophen plus codeine (500/30 mg) for a respiratory infection. He was
      admitted to the emergency room and was treated with metamizol and pantoprazole. A
      few minutes after receiving intravenous doses of both drugs he developed a
      maculopapular and itching eruption with facial angioedema. Laboratory tests
      showed high levels of serum amylase, GOT, GPT and total bilirubin. Serological
      tests for several viruses showed no evidence of recent infection. Ultrasonography
      was negative for biliary lithiasis and showed only cholecystectomy performed in
      2000. The patient was sent to our department where skin prick and oral challenge
      tests were performed with negative results. For ethical reasons, oral challenge
      with codeine was not carried out. We believe that our patient had codeine-induced
      pancreatitis. The most likely underlying pathophysiological mechanism was
      probably codeine-induced spasm of the sphincter of Oddi combined with sphincter
      of Oddi dysfunction related to a previous cholecystectomy. Allergy departments
      should be aware of possible non-immunological adverse.

PMID- 15946635
TI  - cDNA cloning and expression pattern of pi-class glutathione S-transferase in the
      freshwater bivalves Unio tumidus and Corbicula fluminea.
AB  - Glutathione S-transferases (GSTs) are enzymes involved in major detoxification
      reactions of xenobiotics in many organisms. The aim of this work was the
      identification of GST transcripts in the freshwater bivalves Unio tumidus and
      Corbicula fluminea. We used degenerated primers designed in the highly conserved
      regions of GST to amplify the corresponding mRNA. Full-length coding sequences
      were obtained by 5' and 3' rapid amplification of cDNA ends. In the two species,
      the GST cDNAs identified encoded a protein of 205 amino acids. The comparison of
      the deduced amino acid sequences with GSTs from other species showed that the
      enzymes belong to the pi-class and the amino acids defining the binding sites of
      glutathione (G-site) and for xenobiotic substrates (H-site) are highly conserved.
      Specific amplifications of the GST mRNA from U. tumidus and C. fluminea were
      performed on the digestive gland, the excretory system and the gills. For each
      mussel, the results revealed that the pi-class GSTs are expressed at the same
      level in the three tissues.

PMID- 15946636
TI  - Molecular cloning and characterization of alpha-class glutathione S-transferase
      genes from the hepatopancreas of red sea bream, Pagrus major.
AB  - Two distinct cDNAs corresponding to GSTA1 and GSTA2 genes encoding glutathione S
      transferases (GSTs) from the hepatopancreas of red sea bream, Pagrus major were
      cloned and sequenced. A comparison of the nucleotide sequences of GSTA1 and GSTA2
      revealed 98% identity and their derived amino acid sequences had 96% similarity.
      Both genes could be classified as alpha-class GSTs on the basis of their amino
      acid sequence identity with other species. Genomic DNA cloning showed that both
      GSTA1 and GSTA2 genes consisted of six exons and five introns. In a comparison of
      genomic DNAs, the structures of GSTA1 and GSTA2 differed. In addition, Southern
      blot analysis indicated that at least two kinds of alpha-class GSTs existed in
      the P. major genome. In order to biochemically characterize the recombinant
      enzymes (pmGSTA1-1 and pmGSTA2-2), both clones were highly expressed in
      Escherichia coli. The purified pmGSTA1-1 and pmGSTA2-2 exhibited glutathione
      conjugating activity toward 1-chloro-2,4-dinitrobenzene and glutathione
      peroxidase activity toward cumene hydroperoxide, while neither pmGSTs show
      detectable activity toward 1,2-dichloro-4-nitrobenzene, ethacrynic acid, 4
      hydroxynonenal, or p-nitrobenzyl chloride. Despite their high level of amino acid
      sequence identity, the pmGSTs had quite different enzyme-kinetic parameters.

PMID- 15946637
TI  - Characteristics of rear-end accidents at signalized intersections using multiple
      logistic regression model.
AB  - Multi-vehicle rear-end accidents constitute a substantial portion of the
      accidents occurring at signalized intersections. To examine the accident
      characteristics, this study utilized the 2001 Florida traffic accident data to
      investigate the accident propensity for different vehicle roles (striking or
      struck) that are involved in the accidents and identify the significant risk
      factors related to the traffic environment, the driver characteristics, and the
      vehicle types. The Quasi-induced exposure concept and the multiple logistic
      regression technique are used to perform this analysis. The results showed that
      seven road environment factors (number of lanes, divided/undivided highway,
      accident time, road surface condition, highway character, urban/rural, and speed
      limit), five factors related to striking role (vehicle type, driver age,
      alcohol/drug use, driver residence, and gender), and four factors related to
      struck role (vehicle type, driver age, driver residence, and gender) are
      significantly associated with the risk of rear-end accidents. Furthermore, the
      logistic regression technique confirmed several significant interaction effects
      between those risk factors.

PMID- 15946638
TI  - Mobile phone use-effects of handheld and handsfree phones on driving performance.
AB  - The study was concerned with effects of handsfree and handheld mobile phone
      dialling and conversation in simulated driving. In the main experiment dealing
      with conversation, 48 participants drove a distance of about 70 km on a route
      which led through urban and rural environments. In the dialling experiment, the
      participants drove a distance of 15 km on a rural two-lane road. The experimental
      design was mixed with phone mode as a between-subjects factor and phone use
      (yes/no) as a within-subjects factor. Performance on a peripheral detection task
      (PDT) while driving was impaired by dialling and conversation for both phone
      modes, interpreted as an increase in mental workload. Driving performance was
      impaired by dialling--lateral position deviation increased in a similar way for
      both phone modes. Conversation had, however, opposite effects--lateral position
      deviation decreased in a similar way for both phone modes. Driving speed
      decreased as an effect of dialling with the greatest effect for handsfree phone
      mode. Conversation also caused reduced speed, but only for handheld phone mode.
      The effects on speed can be interpreted as a compensatory effort for the
      increased mental workload. In spite of the compensatory behaviour, mental
      workload was still markedly increased by phone use. Subjective effects of
      dialling and conversation were also analysed. Most participants reported a speed
      decrease but no effect on lateral position deviation as an effect of dialling or
      conversation. In the conversation experiment, driving performance was rated
      better for handsfree than for handheld mode. In the dialling experiment, no
      difference between the two phone modes appeared.

PMID- 15946639
TI  - The role of CO2 in cobalt-catalyzed peroxidations.
AB  - Augmentation, by CO(2)/HCO(3)(-), of Co(II)-catalyzed peroxidations was explored
      to clarify whether the rate enhancement was due to CO(2) or to HCO(3)(-). The
      rate of oxidation of NADH by Co(II) plus H(2)O(2), in Tris or phosphate, was
      markedly enhanced by CO(2)/HCO(3)(-). Phosphate was seen to inhibit the Co(II)
      catalyzed peroxidation, probably due to its sequestration of the Co(II). When
      CO(2) was used, there was an initial burst of NADH oxidation followed by a slower
      linear rate. The presence of carbonic anhydrase eliminated this initial burst;
      establishing that CO(2) rather than HCO(3)(-) was the species responsible for the
      observed rate enhancements. Both kinetic and spectral data indicated that Co(II)
      was converted by H(2)O(2) into a less active form from which Co(II) could be
      regenerated. This less active form absorbed in both the UV and visible regions,
      and is assumed to be a peroxy bridged binuclear complex. The rate of formation of
      this absorbing form was increased by HCO(3)(-)/CO(2). A minimal mechanism
      consistent with these observations is proposed.

PMID- 15946640
TI  - The molybdate binding protein Mop from Haemophilus influenzae--biochemical and
      thermodynamic characterisation.
AB  - The protein Mop from Haemophilus influenzae is a member of the molbindin family
      of proteins. Using isothermal titration calorimetry (ITC), Mop was observed to
      bind molybdate at two distinct sites with a stoichiometry of 8 mol molybdate per
      Mop hexamer. Six moles of molybdate bound endothermically at high affinity sites
      (K(a)=8.5 x 10(7)M(-1)), while 2 mol of molybdate bound exothermically at lower
      affinity sites (K(a)=3.7 x 10(7)M(-1)). Sulphate was also found to bind weakly at
      the higher affinity sites. ITC revealed that the affinity of molybdate binding to
      the endothermic site decreased with increasing pH and was accompanied by the
      transfer from the buffer to the protein of one proton per Mop monomer. These
      kinetic and thermodynamic results are interpreted with reference to molbindin
      crystal structures and data concerning molbindin binding affinities. Mop binds
      molybdate with high specificity, capacity, and affinity which indicates that Mop
      has a role as an intracellular molybdate binding protein involved in oxyanion
      homeostasis.

PMID- 15946641
TI  - Restrained molecular dynamics studies on complex of adriamycin with DNA hexamer
      sequence d-CGATCG.
AB  - Adriamycin is an anthracycline anticancer drug used widely for solid tumors in
      spite of its adverse side effects. The solution structure of 2:1 adriamycin-d
      (CGATCG)(2) complex has been studied by restrained molecular dynamics
      simulations. The restraint data set consists of several intramolecular and
      intermolecular nuclear Overhauser enhancement cross-peaks obtained from two
      dimensional nuclear magnetic resonance spectroscopy data. The drug is found to
      intercalate between CG and GC base pairs at two d-CpG sites. The drug-DNA complex
      is stabilized via specific hydrogen bonding and van der Waal's interactions
      involving 4OCH(3), O5, 6OH, and NH(3)(+) moiety of daunosamine sugar, and rings A
      protons. The O-glycosidic bond C7-O7-C1'-C2' lies in the range 138 degrees -160
      degrees during the course of simulations. The O6-H6...O5 hydrogen bond is stable
      while O11-H11...O12 hydrogen bond is not favored. The intercalating base pairs
      are buckled and minor groove is wider in the complex. The phosphate on one strand
      at intercalation site C1pG2 is in B(I) conformation and the phosphates directly
      lying on opposite strand is in B(II) conformation. The phosphorus on adjacent
      site G2pA3 is in B(II) conformation and hence a distinct pattern of B(I) and
      B(II) conformations is induced and stabilized. The role of various functional
      groups by which the molecular action is mediated has been discussed and
      correlated to the available biochemical evidence.

PMID- 15946642
TI  - Differential roles of 3H-1,2-dithiole-3-thione-induced glutathione, glutathione S
      transferase and aldose reductase in protecting against 4-hydroxy-2-nonenal
      toxicity in cultured cardiomyocytes.
AB  - 4-hydroxy-2-nonenal (HNE) plays an important role in the pathogenesis of cardiac
      disorders. While conjugation with glutathione (GSH) catalyzed by GSH S
      transferase (GST) has been suggested to be a major detoxification mechanism for
      HNE in target cells, whether chemically upregulated cellular GSH and GST afford
      protection against HNE toxicity in cardiac cells has not been investigated. In
      addition, the differential roles of chemically induced GSH and GST as well as
      other cellular factors in detoxifying HNE in cardiomyocytes are unclear. In this
      study, we have characterized the induction of GSH and GST by 3H-1,2-dithiole-3
      thione (D3T) and the protective effects of the D3T-elevated cellular defenses on
      HNE-mediated toxicity in rat H9C2 cardiomyocytes. Treatment of cardiomyocytes
      with D3T resulted in a significant induction of both GSH and GST as well as the
      mRNA expression of gamma-glutamylcysteine ligase catalytic subunit and GSTA. Both
      GSH and GST remained elevated for at least 72 h after removal of D3T from the
      culture media. Treatment of cells with HNE led to a significant decrease in cell
      viability and an increased formation of HNE-protein adducts. Pretreatment of
      cells with D3T dramatically protected against HNE-mediated cytotoxicity and
      protein-adduct formation. HNE treatment caused a significant decrease in cellular
      GSH level, which preceded the loss of cell viability. Either depletion of
      cellular GSH by buthionine sulfoximine (BSO) or inhibition of GST by
      sulfasalazine markedly sensitized the cells to HNE toxicity. Co-treatment of
      cardiomyocytes with BSO was found to completely block the D3T-mediated GSH
      elevation, which however failed to reverse the cytoprotective effects of D3T,
      suggesting that other cellular factor(s) might be involved in D3T
      cytotprotection. In this regard, D3T was shown to induce cellular aldose
      reductase (AR). Surprisingly, inhibition of AR by sorbinil failed to potentiate
      HNE toxicity in cardiomyocytes. In contrast, sorbinil dramatically augmented HNE
      cytotoxicity in cells with GSH depletion induced by BSO. Similarly, in BSO
      treated cells, D3T cytoprotection was also largely reversed by sorbinil,
      indicating that AR played a significant role in detoxifying HNE only under the
      condition of GSH depletion in cardiomyocytes. Taken together, this study
      demonstrates that D3T can induce GSH, GST, and AR in cardiomyocytes, and that the
      above cellular factors appear to play differential roles in detoxification of HNE
      in cardiomyocytes.

PMID- 15946643
TI  - Effect of insulin and glucagon on accumulation of uroporphyrin and coproporphyrin
      from 5-aminolevulinate in hepatocyte cultures.
AB  - Primary cultures of chick embryo hepatocytes have been used to study the
      mechanisms by which various drugs and other chemicals cause accumulation of
      porphyrin intermediates of the heme pathway. When these cultures are incubated
      with the heme precursor, 5-aminolevulinic acid (ALA), there is a major
      accumulation of protoporphyrin. However, in the presence of ALA, addition of
      insulin caused a striking increase in accumulation of uroporphyrin I and
      coproporphyrin III, whereas addition of glucagon mainly caused an increase in
      uroporphyrin I. Treatment with both insulin and glucagon resulted in additive
      increases in uroporphyrin, but not coproporphyrin. Antioxidants abolished the
      uroporphyrin I accumulation and increased coproporphyrin III. Insulin caused an
      increase in uptake of ALA and an increase in porphobilinogen accumulation,
      suggesting that the accumulation of uroporphyrin I is due to increased flux
      through the heme pathway. Apparently, this increased flux could particularly
      affect the utilization of the intermediate hydroxymethylbilane, which would
      result in accumulation of uroporphyrin I.

PMID- 15946644
TI  - Linking tricyclic antidepressants to ionotropic glutamate receptors.
AB  - Although tricyclic antidepressants have been in existence since the 1940s when
      they were discovered upon screening iminodibenzyl derivatives for other potential
      therapeutic uses, their mechanism of action has remained unclear [A. Goodman
      Gilman, T.W. Rall, A.S. Nies, P. Taylor, Goodman and Gilman's The Pharmacological
      Basis of Therapeutics, eighth ed., Pergamon Press, New York, 1990]. In addition
      to their ability to hinder the reuptake of biogenic amines, there is mounting
      evidence that the tricyclic antidepressants inhibit glutamate transmission. Here,
      intrinsic tryptophan fluorescence spectroscopy is used to document the binding of
      desipramine, a member of the tricyclic antidepressant family, to a well-defined
      extracellular glutamate binding domain (S1S2) of the GluR2 subunit of the amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid receptor. The binding is distinct from
      those of other known effectors of the receptor, including the endogenous sulfated
      neurosteroids pregnenolone sulfate and 3alpha-hydroxy-5beta-pregnan-20-one
      sulfate, and is consistent with a conformational change upon binding that is
      allosterically transmitted to the channel region of the receptor.

PMID- 15946645
TI  - Post-transcriptional regulation of macrophage ABCA1, an early response gene to
      IFN-gamma.
AB  - Interferon-gamma (IFN-gamma) down-regulates receptors associated with reverse
      cholesterol transport including ABCA1. In the present study, the kinetics and
      mechanism of ABCA1 down-regulation were determined in mouse peritoneal
      macrophages. IFN-gamma decreased ABCA1 mRNA 1h following IFN-gamma addition and
      was maximally reduced by 3h. Down-regulation was protein synthesis dependent and
      involved post-transcriptional processes. ABCA1 message had a T(1/2) of 115 min in
      actinomycin treated cells that was reduced to a T(1/2) of 37 min by IFN-gamma.
      The decrease in message stability was also associated with a rapid loss of ABCA1
      protein, significant 3h following IFN-gamma addition. The kinetics of ABCA1
      message and protein decrease was consistent with the early IFN-gamma-induced
      changes in Stat1 phosphorylation and nuclear translocation observed in these
      cells. Therefore, ABCA1 can be considered as an early response gene to macrophage
      activation by IFN-gamma with down-regulation occurring by message
      destabilization.

PMID- 15946646
TI  - Lysophosphatidylserine stimulates leukemic cells but not normal leukocytes.
AB  - In this study, we observed that lysophosphatidylserine (LPS) stimulated
      intracellular calcium ([Ca(2+)](i)) increase in leukemic cells but not in normal
      human peripheral blood mononuclear cells. LPS also stimulated [Ca(2+)](i)
      increase in human leukemic THP-1 cells. LPS-stimulated [Ca(2+)](i) increase was
      inhibited by U-73122 but not by U-73343. LPS also stimulated inositol phosphates
      formation in THP-1 cells, suggesting that LPS stimulates calcium signaling via
      phospholipase C activation. Moreover, pertussis toxin (PTX) completely inhibited
      [Ca(2+)](i) increase by LPS, indicating the activation of PTX-sensitive G
      proteins. We also found that LPS-induced [Ca(2+)](i) increase was completely
      inhibited by suramin, suggesting G-protein coupled receptor activation. Since LPS
      specifically stimulates PTX-sensitive G-proteins, phospholipase C-dependent
      [Ca(2+)](i) increase in leukemic cells but not normal peripheral blood
      leukocytes, LPS receptor may be associated with leukemia.

PMID- 15946647
TI  - Epigallocatechin-3-O-gallate disrupts stress fibers and the contractile ring by
      reducing myosin regulatory light chain phosphorylation mediated through the
      target molecule 67 kDa laminin receptor.
AB  - Epigallocatechin-3-O-gallate (EGCG), a major polyphenol of green tea, has been
      shown to inhibit the growth of various cancer cell lines. We show here that EGCG
      induced the disruption of stress fibers and decreased the phosphorylation of the
      myosin II regulatory light chain (MRLC) at Thr18/Ser19, which is necessary for
      both contractile ring formation and cell division. Indirect immunofluorescence
      analysis revealed that EGCG inhibited the concentration of both F-actin and the
      phosphorylated MRLC in the cleavage furrow at the equator of dividing cells. In
      addition, EGCG increased the percentages of cells in the G(2)/M phase and
      inhibited cell growth. Recently, we have demonstrated that the anticancer
      activity of EGCG is mediated by the metastasis-associated 67kDa laminin receptor
      (67LR). To explore whether the effect of EGCG is mediated by the 67LR, we
      transfected cells with short hairpin RNA (shRNA) expression vector to
      downregulate 67LR expression. When the 67LR was silenced, the suppressive effect
      of EGCG on the MRLC phosphorylation was significantly attenuated. These results
      suggest that EGCG inhibits the cell growth by reducing the MRLC phosphorylation
      and this effect is mediated by the 67LR.

PMID- 15946648
TI  - Crystal structure of heterotetrameric sarcosine oxidase from Corynebacterium sp.
      U-96.
AB  - Sarcosine oxidase from Corynebacterium sp. U-96 is a heterotetrameric enzyme.
      Here we report the crystal structures of the enzyme in complex with
      dimethylglycine and folinic acid. The alpha subunit is composed of two domains,
      contains NAD(+), and binds folinic acid. The beta subunit contains
      dimethylglycine, FAD, and FMN, and these flavins are approximately 10A apart. The
      gamma subunit is in contact with two domains of alpha subunit and has possibly a
      folate-binding structure. The delta subunit contains a single atom of zinc and
      has a Cys(3)His zinc finger structure. Based on the structures determined and on
      the previous works, the structure-function relationship on the heterotetrameric
      sarcosine oxidase is discussed.

PMID- 15946649
TI  - Generation of skeletal muscle from transplanted embryonic stem cells in
      dystrophic mice.
AB  - Embryonic stem (ES) cells have great therapeutic potential because of their
      capacity to proliferate extensively and to form any fully differentiated cell of
      the body, including skeletal muscle cells. Successful generation of skeletal
      muscle in vivo, however, requires selective induction of the skeletal muscle
      lineage in cultures of ES cells and following transplantation, integration of
      appropriately differentiated skeletal muscle cells with recipient muscle.
      Duchenne muscular dystrophy (DMD), a severe progressive muscle wasting disease
      due to a mutation in the dystrophin gene and the mdx mouse, an animal model for
      DMD, are characterized by the absence of the muscle membrane associated protein,
      dystrophin. Here, we show that co-culturing mouse ES cells with a preparation
      from mouse muscle enriched for myogenic stem and precursor cells, followed by
      injection into mdx mice, results occasionally in the formation of normal,
      vascularized skeletal muscle derived from the transplanted ES cells. Study of
      this phenomenon should provide valuable insights into skeletal muscle development
      in vivo from transplanted ES cells.

PMID- 15946650
TI  - The yeast multicopper oxidase Fet3p and the iron permease Ftr1p physically
      interact.
AB  - High affinity iron uptake in yeast is carried out by a multicomponent system
      formed by the ferroxidase Fet3p and the iron permease Ftr1p. The currently
      accepted model predicts that Fet3p and Ftr1p are functionally associated,
      however, a structural interaction between these two proteins has not been proven
      yet. The methylotrophic yeast Pichia pastoris has been used to perform cross
      linking studies aimed to demonstrate the existence of a Fet3p-Ftr1p complex.
      Cross-linking of membrane suspensions with the membrane-impermeable reagents
      DTSSP and BS(3) has evidenced the presence of a high molecular weight band with
      Fet3p oxidase activity. This band has been purified and subjected to N-terminal
      sequence analysis. Two sequences were found in the cross-linked species, one of
      which could be assigned to Fet3p and the other to Ftr1p. This is the first
      experimental demonstration that Fet3p and Ftr1p are physically associated.

PMID- 15946651
TI  - Monoclonal side population progenitors isolated from human fetal pancreas.
AB  - The side population (SP) phenotype might represent a common molecular feature for
      a wide variety of stem cells. The aim of this study was to investigate whether
      monoclonal SP progenitor cells were established from human fetal pancreas. Islet
      like cell clusters (ICCs) were isolated from human fetal pancreas. Monolayer
      epithelium-like cells were obtained from the ICCs and passaged thereafter. Single
      SP or non-SP cells were sorted from these cells at the sixth passage. The rate of
      clone formation was about 2.7% for the SP cells, whereas there was no clone
      formation for the non-SP cells. The SP cell clones were further expanded for more
      than 15 passages and induced for differentiation into cells with characteristics
      of pancreatic beta-cells. We show for the first time that the monoclonal SP
      progenitors are established from human fetal pancreas. Therefore, this study may
      offer a novel method to purify pancreatic progenitor cells from human tissues.

PMID- 15946652
TI  - Tissue engineering strategies for cartilage generation--micromass and three
      dimensional cultures using human chondrocytes and a continuous cell line.
AB  - Utilizing ATDC5 murine chondrogenic cells and human articular chondrocytes, this
      study sought to develop facile, reproducible three-dimensional models of
      cartilage generation with the application of tissue engineering strategies,
      involving biodegradable poly(glycolic acid) scaffolds and rotating wall
      bioreactors, and micromass pellet cultures. Chondrogenic differentiation,
      assessed by histology, immunohistochemistry, and gene expression analysis, in
      ATDC5 and articular chondrocyte pellets was evident by the presence of distinct
      chondrocytes, expressing Sox-9, aggrecan, and type II collagen, in lacunae
      embedded in a cartilaginous matrix of type II collagen and proteoglycans. Tissue
      engineered explants of ATDC5 cells were reminiscent of cartilaginous structures
      composed of numerous chondrocytes, staining for typical chondrocytic proteins, in
      lacunae embedded in a matrix of type II collagen and proteoglycans. In
      comparison, articular chondrocyte explants exhibited areas of Sox-9, aggrecan,
      and type II collagen-expressing cells growing on fleece, and discrete islands of
      chondrocytic cells embedded in a cartilaginous matrix.

PMID- 15946653
TI  - Oral flavonoids delay recovery from experimental autoimmune encephalomyelitis in
      SJL mice.
AB  - Flavonoids are food components that appear to have potential beneficial health
      effects. There is a range of in vitro studies supporting the anti-oxidant and
      anti-inflammatory properties of flavonoids. Previously, we demonstrated that in
      vitro flavonoids, including luteolin and apigenin, inhibit proliferation and IFN
      gamma production by murine and human autoimmune T cells. In the present study, we
      examined the effects of oral flavonoids as well as of curcumin on autoimmune T
      cell reactivity in mice and on the course of experimental autoimmune
      encephalomyelitis (EAE), a model for multiple sclerosis. Continuous oral
      administration of flavonoids significantly affected antigen-specific
      proliferation and IFN-gamma production by lymph node-derived T cells following
      immunization with an EAE-inducing peptide. Both luteolin and apigenin suppress
      proliferative responses as they did in vitro, whereas IFN-gamma production on the
      other hand was enhanced. Other flavonoids exerted differential effects on
      proliferation and IFN-gamma production. The effects of flavonoids and curcumin on
      EAE were assessed using either passive transfer of autoimmune T cells or active
      disease induction. In passive EAE, flavonoids led to delayed recovery of clinical
      symptoms rather than to any reduction in disease. In active EAE, the effects were
      less pronounced but also, in this case, the flavonoid hesperitin delayed
      recovery. Oral curcumin had overall mild but beneficial effects. Our results
      indicate that oral flavonoids fail to beneficially influence the course of EAE in
      mice but, instead, suppress recovery from acute inflammatory damage.

PMID- 15946654
TI  - Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase
      production by down-regulating JNK-AP-1 signaling in human chondrocytes.
AB  - The development of osteoarthritis (OA) has recently been implicated as a result
      of immune-mediated damage of chondrocytes and their supporting matrixes. Pro
      inflammatory cytokines like interleukin (IL)-1 and tumor necrosis factor alpha
      (TNF-alpha) play pivotal roles in immunopathogenesis of OA. Because vitamins
      preserving anti-oxidative effects are suggested to provide protection in OA
      patients from joint damage, in the present study, we examined the effects and
      mechanisms of all-trans retinoic acid (t-RA) in suppressing pro-inflammatory
      cytokine-induced matrix metalloproteinases (MMPs) production in human
      chondrocytes. Chondrocytes were prepared from cartilage specimens of OA patients
      receiving total hip or total knee replacement. The protein concentration was
      measured by ELISA, the mRNA expression by reverse transcriptase-polymerase chain
      reaction, the protein expression by Western blotting, the transcription factor
      DNA-binding activity by electrophoretic mobility shift assay and the protein
      kinase activity by kinase assay. We showed that both MMP-1 and MMP-13 mRNA
      expression, protein production and enzyme activity induced by either IL-1 or TNF
      alpha were suppressed by t-RA or different retinoid derivatives. The molecular
      investigation revealed that the t-RA-mediated suppression was likely through
      blocking p38 kinase and c-Jun N-terminal kinase-activator protein-1 signaling
      pathways. In contrast, t-RA had no effect on extracellular signal-regulated
      kinase activity, nuclear factor (kappa)B (NF-(kappa)B) DNA-binding activity and
      I(kappa)B(alpha) degradation. Furthermore, we showed that t-RA could reduce IL-1
      induced TNF-alpha production in chondrocytes. Our results suggest that vitamin A
      may protect OA patients from pro-inflammatory cytokine-mediated damage of
      chondrocytes and their supporting matrixes.

PMID- 15946655
TI  - Treatment with 1,2,3,4-tetrahydroisoquinolone affects the levels of nitric oxide,
      S-nitrosothiols, glutathione and the enzymatic activity of gamma-glutamyl
      transpeptidase in the dopaminergic structures of rat brain.
AB  - Depletion of glutathione (GSH), nitrosative stress and chronic intoxication with
      some neurotoxins have been postulated to play a major role in the pathogenesis of
      Parkinson's disease. This study aimed to examine the effects of acute and chronic
      treatments with 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo-/exogenous
      substance suspected of producing Parkinsonism in human, on the levels of nitric
      oxide (NO), S-nitrosothiols and glutathione (GSH) in the whole rat brain and in
      its dopaminergic structures. TIQ administered at a dose of 50 mg/kg i.p.
      significantly increased the tissue concentrations of NO and GSH in the substantia
      nigra (SN), striatum (STR) and cortex (CTX) of rats receiving this compound both
      acutely and chronically. Moreover, it decreased the level of oxidized glutathione
      (GSSG) and enhanced GSH:GSSG ratio affecting in this way the redox state of brain
      cells. TIQ also increased the level of S-nitrosothiols when measured in the whole
      rat brain and CTX, although it markedly decreased their level in the STR after
      both treatments. Inhibition of the constitutive NO synthase by l-NAME in the
      presence of TIQ caused decreases in GSH and S-nitrosothiol levels in the brain.
      The latter effect shows that the TIQ-mediated increases in GSH and S-nitrosothiol
      concentrations were dependent on the enhanced NO level. The above-described
      results suggest that TIQ can act as a modulator of GSH, NO and S-nitrosothiol
      levels but not as a parkinsonism-inducing agent in the rat brain.

PMID- 15946656
TI  - Effect of buformin and metformin on formation of advanced glycation end products
      by methylglyoxal.
AB  - BACKGROUND: The formation and accumulation of advanced glycation end products
      (AGE) in various tissues are known to be involved in the aging process and
      complications of long-term diabetes. Aminoguanidine as AGE inhibitors was first
      studied, and metformin as biguanide compounds have been reported to react with
      reactive dicarbonyl precursors such as methylglyoxal. METHODS: We studied the
      effects of the biguanides of buformin and metformin on AGE formation by the
      methods of specific fluorescence, and enzyme-linked immunosorbent assay and a
      Western blot analysis using the anti-AGE antibody after incubating BSA or RNase
      with methylglyoxal. RESULTS: Buformin is a more potent inhibitor of AGE formation
      than metformin, and suggests that the amino group of buformin trap the carbonyl
      group of methylglyoxal to suppress formation of AGE. CONCLUSION: In addition to
      that of metformin, buformin may be clinically useful to prevent diabetic
      complications.

PMID- 15946657
TI  - Functional proteomics.
AB  - BACKGROUND: With the increase in the number of genome sequencing projects, there
      is a concomitant exponential growth in the number of protein sequences whose
      function is still unknown. Functional proteomics constitutes an emerging research
      area in the proteomic field whose approaches are addressed towards two major
      targets: the elucidation of the biological function of unknown proteins and the
      definition of cellular mechanisms at the molecular level. METHODS: The
      identification of interacting proteins in stable complexes in vivo is essentially
      achieved by affinity-based procedures. The basic idea is to express the protein
      of interest with a suitable tag to be used as a bait to fish its specific
      partners out from a cellular extract. Individual components within the multi
      protein complex can then be identified by mass spectrometric methodologies.
      RESULTS AND CONCLUSIONS: The association of an unknown protein with partners
      belonging to a specific protein complex involved in a particular mechanism is
      strongly suggestive of the biological function of the protein. Moreover, the
      identification of protein partners interacting with a given protein will lead to
      the description of cellular mechanisms at the molecular level. The next goal will
      be to generate animal models bearing a tagged form of the bait protein.

PMID- 15946658
TI  - A proteomic approach in the study of an animal model of Parkinson's disease.
AB  - BACKGROUND: The aetiology of Parkinson's disease (PD), an age-related disorder
      characterized by a progressive degeneration of dopaminergic neurons of the
      substantia nigra (SN) pars compacta, remains unclear. Current treatments, such as
      administration of L-DOPA, are only symptomatic and do not stop or delay the
      progressive loss of neurons. In fact, it has been suggested that the dopamine
      precursor L-DOPA, increases generation of reactive oxygen species (ROS) leading
      to further neuronal damage. A similar loss in nigrostriatal dopaminergic neurons
      is produced on intracerebral administration of the catecholaminergic neurotoxin 6
      hydroxydopamine (6-OHDA). In an animal model of PD, termed 'the hemiparkinsonian
      rat', unilateral injection of 6-OHDA into the nigrostriatal pathway results in
      extensive loss of dopaminergic cells in the ipsolateral SN. In an attempt to
      identify some of the proteins that are involved in dopaminergic neuronal death,
      we used the proteomic methods to analyze this animal model of PD. METHODS: Five
      hemiparkinsonian rats were obtained by intranigral stereotaxic injection of 6
      OHDA. The right 6-OHDA-lesioned substantia nigra and striatum tissues along with
      the left, unlesioned controlateral tissues, were excised and homogenized, using
      urea-based buffer, to extract the tissues protein. The separation of the protein
      mixtures and the visualization of the protein patterns obtained were performed
      using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Protein
      profiles of control and treated tissues were compare by the PDQuest 2D-gel
      analysis software (BIO-Rad laboratory). The protein spots showing differential
      expression were analysed by matrix assisted laser desorption/ionizing time of
      flight (MALDI-TOF) mass spectrometry. RESULTS: The brain protein extraction and
      solubilization protocol was validated obtaining a satisfactory protein profile.
      In comparison to the normal rats, hemiparkinsonian animals exhibited a different
      expression in alpha-enolase and beta-actin in substantia nigra and striatum,
      respectively. CONCLUSION: The proteomic study of 6-OHDA-induced lesions in the
      nigrostriatial pathway allowed us to identify two proteins, alpha-enolase and
      beta-actin, showing increased levels in the 6-OHDA-lesioned brain tissues
      compared to control. Previous studies described the same proteins as oxidized and
      proteins in Alzheimer's disease (AD) brain. Our preliminary data could mirror
      those results pointing out a common mechanism of neurodegenerative diseases.

PMID- 15946659
TI  - The reporting of serum protein electrophoresis to clinicians.

PMID- 15946660
TI  - Calcium activation of tissue transglutaminase in radioligand binding and enzyme
      linked autoantibody immunoassays in childhood celiac disease.
AB  - BACKGROUND: Conflicting data have been published concerning the effect of calcium
      on binding of autoantibodies to tissue transglutaminase (tTG) in celiac disease
      (CD). METHODS: IgA-tTG and IgG-tTG were measured with radioligand binding assays
      (RBA) using human recombinant (hr) (35)S-tTG produced in lysate of rabbit
      reticulocytes and with guinea pig (gp) tTG ELISA in 51 CD children (median: 5.7
      years) and 35 controls (median: 2.2 years). Assays were performed with and
      without calcium. RESULTS: In hr-tTG RBA, IgA-tTG levels remained unchanged after
      calcium detecting 50/51 CD children and 1/35 controls (p<0.0001). IgG-tTG levels
      decreased with calcium (p<0.0001) in CD children and detected 48/51 with and
      49/51 without calcium as compared to 1/35 controls (p<0.0001). In gp-tTG ELISA,
      levels increased with calcium (p<0.0001) making it possible to detect an
      additional three to a total of 50/51 with IgA-tTG and 13 to 39/51 CD children
      with IgG-tTG compared to 4/35 and 8/35 controls (respectively, p<0.0001). Rabbit
      reticulocytes displayed calcium-dependent tTG activity. CONCLUSIONS: Calcium
      increased binding of IgA-tTG and IgG-tTG in the ELISA test. The reverse effect
      observed in RBA may be explained by competitive binding between calcium activated
      native rabbit reticulocyte tTG and hr (35)S-tTG. tTG autoantibody assays may need
      taking calcium into account for accurate diagnostic sensitivity and specificity
      for CD.

PMID- 15946661
TI  - Pancreatic cancer-associated diabetes mellitus: an open field for proteomic
      applications.
AB  - BACKGROUND: Diabetes mellitus is associated with pancreatic cancer in more than
      80% of the cases. Clinical, epidemiological, and experimental data indicate that
      pancreatic cancer causes diabetes mellitus by releasing soluble mediators which
      interfere with both beta-cell function and liver and muscle glucose metabolism.
      METHODS: We analysed, by matrix-assisted laser desorption ionization time of
      flight (MALDI-TOF), a series of pancreatic cancer cell lines conditioned media,
      pancreatic cancer patients' peripheral and portal sera, comparing them with
      controls and chronic pancreatitis patients' sera. RESULTS: MALDI-TOF analysis of
      pancreatic cancer cells conditioned media and patients' sera indicated a low
      molecular weight peptide to be the putative pancreatic cancer-associated
      diabetogenic factor. The sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis of tumor samples from diabetic and non
      diabetic patients revealed the presence of a 1500 Da peptide only in diabetic
      patients. The amino acid sequence of this peptide corresponded to the N-terminal
      of an S-100 calcium binding protein, which was therefore suggested to be the
      pancreatic cancer-associated diabetogenic factor. CONCLUSIONS: We identified a
      tumor-derived peptide of 14 amino acids sharing a 100% homology with an S-100
      calcium binding protein, which is probably the pancreatic cancer-associated
      diabetogenic factor.

PMID- 15946662
TI  - A single exposure to hyperbaric oxygen does not cause oxidative stress in
      isolated platelets: no effect on superoxide dismutase, catalase, or cellular ATP.
AB  - OBJECTIVES: The aim of the study was to investigate whether a single hyperbaric
      oxygen exposure causes oxidative stress in isolated platelets. DESIGN AND
      METHODS: Isolated horse platelets were exposed to 100% oxygen at 2.2 atmospheres,
      or 100% oxygen under normobaric conditions, or air under normobaric conditions
      for 90 min. RESULTS: There were no differences in platelet SOD activity between
      conditions, but there was a rise in SOD in all cases after 24 h (in control
      platelets at 24 h, SOD was 11.9 +/- 1.9 nmol/min/mg protein compared to initial
      background levels of 8.2 +/- 1.9 nmol/min/mg protein) (P < 0.05). Neither
      platelet catalase activity nor platelet GSH concentration changed over time, nor
      between conditions (catalase activity remained at around 12 units/mg protein, and
      GSH at around 1.58 nmol/mg protein). CONCLUSIONS: These data suggest that a
      single HBO exposure has no detrimental effect on platelet biochemistry, and does
      not cause overt oxidative stress in vitro.

PMID- 15946663
TI  - Mitochondrial DNA in somatic cells: a promising target of routine clinical tests.
AB  - Alterations of mitochondrial DNA have long been considered only from a point of
      view of rare genetic disorders causing neuromyopathy. Recently, alterations of
      mitochondrial DNA have been found in so-called common diseases such as heart
      failure, diabetes, and cancer; some of these alterations are inherited, and some
      are generated and/or accumulated in somatic cells with age. Mitochondrial DNA is
      more vulnerable to alteration than is nuclear DNA. For example, mitochondria
      produce a large amount of reactive oxygen species as an inevitable byproduct of
      oxidative phosphorylation. Therefore, mitochondrial DNA is under much stronger
      oxidative stress than is nuclear DNA. In spite of the importance, it is much less
      elucidated in the mitochondrial genome than in the nuclear genome how the genome
      is maintained. In this review, we focus on maintenance of mitochondrial DNA in
      somatic cells and its clinical importance.

PMID- 15946664
TI  - The interaction between the adaptor protein APS and Enigma is involved in actin
      organisation.
AB  - APS (adaptor protein with PH and SH2 domains) is an adaptor protein
      phosphorylated by several tyrosine kinase receptors including the insulin
      receptor. To identify novel binding partners of APS, we performed yeast two
      hybrid screening. We identified Enigma, a PDZ and LIM domain-containing protein
      that was previously shown to be associated with the actin cytoskeleton. In HEK
      293 cells, Enigma interacted specifically with APS, but not with the APS-related
      protein SH2-B. This interaction required the NPTY motif of APS and the LIM
      domains of Enigma. In NIH-3T3 cells that express the insulin receptor, Enigma and
      APS were partially co-localised with F-actin in small ruffling structures.
      Insulin increased the complex formation between APS and Enigma and their co
      localisation in large F-actin containing ruffles. While in NIH-3T3 and HeLa cells
      the co-expression of both Enigma and APS did not modify the actin cytoskeleton
      organisation, expression of Enigma alone led to the formation of F-actin
      clusters. Similar alteration in actin cytoskeleton organisation was observed in
      cells expressing both Enigma and APS with a mutation in the NPTY motif. These
      results identify Enigma as a novel APS-binding protein and suggest that the
      APS/Enigma complex plays a critical role in actin cytoskeleton organisation.

PMID- 15946665
TI  - Upregulation of human mitochondrial NADH dehydrogenase subunit 5 in intestinal
      epithelial cells is modulated by Vibrio cholerae pathogenesis.
AB  - Cholera still remains an important global predicament especially in India and
      other developing countries. Vibrio cholerae, the etiologic agent of cholera,
      colonizes the small intestine and produces an enterotoxin that is largely
      responsible for the watery diarrheal symptoms of the disease. Using RNA
      arbitrarily primed PCR, ND5 a mitochondria encoded subunit of complex I of the
      mitochondrial respiratory chain was found to be upregulated in the human
      intestinal epithelial cell line Int407 following exposure to V. cholerae. The
      upregulation of ND5 was not observed when Int407 was infected with Escherichia
      coli strains. Incubation with heat-killed V. cholerae or cholera toxin or culture
      supernatant also showed no such upregulation indicating the involvement of live
      bacteria in the process. Infection of the monolayer with aflagellate non-motile
      mutant of V. cholerae O395 showed a very significant (59-fold) downregulation of
      ND5. In contrast, a remarkable upregulation of ND5 expression (200-fold) was
      observed in a hyperadherent icmF insertion mutant with reduced motility. V.
      cholerae cheY4 null mutant defective in adherence and motility also resulted in
      significantly reduced levels of ND5 expression while mutant with the cheY4 gene
      duplicated showing increased adherence and motility resulted in increased
      expression of ND5. These results clearly indicate that both motility and
      adherence to intestinal epithelial cells are possible triggering factors
      contributing to ND5 mRNA expression by V. cholerae. Interestingly infection with
      insertion mutant in the gene coding for ToxR, the master regulator of virulence
      in V. cholerae resulted in significant downregulation of ND5 expression. However,
      infection with ctxA or toxT insertion mutants did not show any significant
      changes in ND5 expression compared to wild-type. Almost no expression of ND5 was
      observed in case of mutation in the gene coding for OmpU, a ToxR activated
      protein. Thus, infection of Int407 with virulence mutant strains of V. cholerae
      revealed that the ND5 expression is modulated by the virulence of V. cholerae in
      a ToxT independent manner. Although no difference in the mitochondrial copy
      number could be detected between infected and uninfected cells, the modulation of
      the expression of other mitochondrial genes were also observed. Incidentally,
      upon V. cholerae infection, complex I activity was found to increase about 3
      folds after 6 h. This is the first report of alteration in mitochondrial gene
      expression upon infection of a non-invasive enteric bacterium like V. cholerae
      showing its modulation with adherence, motility and virulence of the organism.

PMID- 15946666
TI  - Induced resistance to the antimicrobial peptide lactoferricin B in Staphylococcus
      aureus.
AB  - This study was designed to investigate inducible intrinsic resistance against
      lactoferricin B in Staphylococcus aureus. Serial passage of seven S. aureus
      strains in medium with increasing concentrations of peptide resulted in an
      induced resistance at various levels in all strains. The induced resistance was
      unstable and decreased relatively rapidly during passages in peptide free medium
      but the minimum inhibitory concentration remained elevated after thirty passages.
      Cross-resistance to penicillin G and low-level cross-resistance to the
      antimicrobial peptides indolicidin and Ala(8,13,18)-magainin-II amide [corrected]
      was observed. No cross-resistance was observed to the human cathelicidin LL-37.
      In conclusion, this study shows that S. aureus has intrinsic resistance
      mechanisms against antimicrobial peptides that can be induced upon exposure, and
      that this may confer low-level cross-resistance to other antimicrobial peptides.

PMID- 15946667
TI  - Regulation and activity of cytosolic 5'-nucleotidase II. A bifunctional
      allosteric enzyme of the Haloacid Dehalogenase superfamily involved in cellular
      metabolism.
AB  - In many vertebrate tissues, cytosolic 5'-nucleotidase II (cN-II) either
      hydrolyses or phosphorylates a number of purine (monophosphorylated) nucleosides
      through a scheme common to the Haloacid Dehalogenase superfamily members. It
      possesses a pivotal role in purine cellular metabolism and it acts on anti
      tumoural and antiviral nucleoside analogues, thus being of potential therapeutic
      importance. cN-II is Mg2+-dependent, regulated and stabilised by several factors
      such as allosteric effectors ATP and 2,3-DPG, although these are not directly
      involved in the reaction stoichiometry. We review herein the experimental
      knowledge currently available about this remarkable enzymatic activity.

PMID- 15946668
TI  - Contrasting effect of fish oil supplementation on the development of
      atherosclerosis in murine models.
AB  - OBJECTIVE: Increased fish oil intake is associated with protection against
      coronary heart disease and sudden death, while effects on atherosclerosis are
      controversial. We explored the effects of supplementing fish oil (rich in n-3
      polyunsaturated fatty acids, PUFA) or corn oil (rich in n-6 PUFA) in two
      different models of atherosclerosis. METHODS AND RESULTS: Sixty-three low density
      lipoprotein receptor-deficient (LDLR(-/-)) mice and sixty-nine apolipoprotein E
      deficient (apoE(-/-)) mice were fed diets without supplementations or
      supplemented with either 1% fish oil or 1% corn oil. In apoE(-/-) mice, neither
      fish oil nor corn oil had any major impact on plasma lipids or atherosclerosis.
      In LDLR(-/-) mice, conversely, the fish oil and the corn oil group had lower
      levels of LDL-cholesterol and triglycerides and had lesser atherosclerosis in the
      aortic root and in the entire aorta (p < 0.01 versus unsupplemented group).
      Atherosclerosis was significantly less in the fish oil group compared with the
      corn oil group when evaluated en face in the aortic arch (area positive to lipid
      staining: 32% with fish oil versus 38% with corn oil; 48% with unsupplemented
      diet). CONCLUSIONS: n-3 and n-6 PUFA supplementation retarded the development of
      atherosclerosis in LDLR(-/-) mice, with a stronger effect seen with n-3 PUFA.
      There was an important strain-dependence of the effect, with no protection
      against atherosclerosis in apoE(-/-) mice.

PMID- 15946669
TI  - Aging, regularity and variability in maximum isometric moments.
AB  - This study examined the variability and regularity of maximum isometric moment
      production of the plantar flexors in young and old subjects. It was hypothesized
      that in the development of maximum isometric moments there would be greater
      regularity in the moment profiles for older subjects compared with young
      subjects, due to the reduced number of motor units present in elderly muscle. Two
      groups of subjects produced three maximal isometric plantar flexions (young:
      n=11, mean age 23.8+/-2.8 years, mean mass 81.2+/-10.4 kg, mean height 1.78+/
      0.05 m; elderly: n=13, mean age 74.0+/-3.3 years, mean mass 78.5+/-3.4 kg, mean
      height 1.73+/-0.05 m). The plateau of the moment-time curve was analyzed for each
      trial. A repeat measures analysis of variance showed the young subjects produced
      statistically greater peak plantar flexion moments than the elderly subjects, but
      similar coefficients of variation. Signal regularity was determined by computing
      the signal's approximate entropy, which demonstrated that the older group had
      greater regularity in their generation of moment profiles. The hypothesis was
      accepted, with a potential explanation for this increased regularity in old age
      being the reduced number of motor units to coordinate.

PMID- 15946670
TI  - Silica nanotubes for lysozyme immobilization.
AB  - Silica nanotubes were synthesized and used as enzyme immobilization carriers. The
      immobilization profiles were described by the adsorption of lysozyme molecules
      from aqueous solution onto the hydrophilic silica surface. The driving force of
      the adsorption, structure changes in the immobilized lysozyme molecules, and
      enzymatic activities were investigated. A study of the zeta potentials of silica
      with and without the immobilized lysozyme showed that there was an increase in
      the isoelectric point with the increase in the loading amount of lysozyme. FTIR
      spectra indicated that protein secondary structure was maintained well in the
      immobilized molecules. It was observed that enzymatic activities first increased
      and then decreased with increasing surface coverage of silica nanotubes by
      lysozyme, which suggested that the overlap and aggregation of lysozyme molecules
      reduced enzymatic activities of the adsorbed lysozyme molecules at high surface
      coverage.

PMID- 15946671
TI  - The effect of mineral composition on the sorption of cesium ions on geological
      formations.
AB  - The sorption of cesium-137 on rock samples, mainly on clay rocks, is determined
      as a function of the mineral composition of the rocks. A relation between the
      mineral groups (tectosilicates, phyllosilicates, clay minerals, carbonates) and
      their cesium sorption properties is shown. A linear model is constructed by which
      the distribution coefficients of the different minerals can be calculated from
      the mineral composition and the net distribution coefficient of the rock. On the
      basis of the distribution coefficients of the minerals the cesium sorption
      properties of other rocks can be predicted.

PMID- 15946672
TI  - Preparation of thermoresponsive core-shell copolymer latex with potential use in
      drug targeting.
AB  - A core-shell copolymer latex with thermal-responsive properties was prepared and
      its potential application as a vehicle for drug targeting was investigated in
      this work, where the crosslinked copolymer of N-isopropylacrylamide (NIPAAm) and
      chitosan was prepared as the core and the copolymer of methacrylic acid (MAA) and
      methyl methacrylate (MMA) was prepared as the shell. By using soapless dispersion
      polymerization, the poly(NIPAAm-chitosan) crosslinked copolymer latex was
      synthesized first. Then the monomers of MAA and MMA were added to continue the
      reaction to obtain the core-shell copolymer latex. The weight ratio of MAA/MMA
      and the concentration of shell monomers (MAA and MMA) in the feed of the reaction
      mixture had been changed to investigate their effects on the particle size,
      reaction rate, zeta-potential, specific surface area, and surface functional
      groups of the latex particles. The swelling and thermoresponsive behavior of the
      film made from these core-shell latices were also studied under different pH
      values of buffer solution. The model drug (caffeine) could be merged inside the
      copolymer particles and protected from releasing through the transport process
      effectively. And the thermoresponsive property of these copolymer particles
      significantly enhances the ligand (protein) conjugation that shows the potential
      of the latex being applied on the targeting drug carrier.

PMID- 15946673
TI  - Wetting of a particle in a thin film.
AB  - When a particle is placed in a thin liquid film on a planar substrate, the liquid
      either climbs or descends the particle surface to satisfy its wetting boundary
      condition. Analytical solutions for the film shape, the degree of particle
      immersion, and the downward force exerted by the wetting meniscus on the particle
      are presented in the limit of small Bond number. When line tension is
      significant, multiple solutions for the equilibrium meniscus position emerge.
      When the substrate is unyielding, a dewetting transition is predicted; that is,
      it is energetically favorable for the particle to rest on top of the film rather
      than remain immersed in it. If the substrate can bend, the energy to drive this
      bending is found in the limits of slow or rapid solid deflection. These results
      are significant in a wide array of disciplines, including controlled delivery of
      drugs to pulmonary airways, the probing of liquid film/particle interface
      properties using particles affixed to AFM tips and the positioning of small
      particles in thin films to create patterned media.

PMID- 15946674
TI  - Novel highly efficient intrabody mediates complete inhibition of cell surface
      expression of the human vascular endothelial growth factor receptor-2 (VEGFR
      2/KDR).
AB  - The human vascular endothelial growth factor receptor-2 (VEGFR-2/KDR) and its
      ligand vascular endothelial growth factor (VEGF) play an essential role in tumor
      angiogenesis and in haematological malignancies. To inhibit VEGF induced
      signalling, intrabodies derived from two scFv fragments recognizing the VEGF
      receptor were generated. When these intrabodies were expressed in endothelial
      cells, they blocked the transport of KDR to the cell surface. We developed a cell
      culture model using porcine aortic endothelial cells overexpressing KDR for
      testing the efficiency of anti-KDR intrabodies. The two intrabodies were targeted
      to the ER and colocalized with the KDR receptor in an intracellular compartment.
      No degradation of the receptor was observed. An immature incomplete glycosylated
      protein of 195 kDa was detected, suggesting that the intrabodies affect the
      maturation of the receptor. Despite the presence of significant amounts of
      receptor protein, the inactivation by one of the two intrabodies was highly
      effective, resulting in complete functional inhibition of KDR and inhibition of
      in vitro angiogenesis. The new intrabody appears to be a powerful tool with which
      to inhibit KDR function.

PMID- 15946675
TI  - Kv4.2 and KChIP2 transcription in individual cardiomyocytes from the rat left
      ventricular free wall.
AB  - Biophysical and genetic evidence suggests that Kv4-KChIP2 heteromeric ion
      channels are the molecular correlate of the dominating fast component of the
      cardiac transient outward K+ current (Itof). Since Itof is one of the essential
      currents contributing to the shape of the cardiac action potential in the rat,
      ferret, dog, and human heart, an important implication of this concept is that
      all ventricular cardiac myocytes from these species express members of the Kv4
      and the KChIP2 gene family. To test this prediction, we developed a modified
      protocol for the collection and subsequent multiplex single-cell RT-PCR
      amplification of RNA from individual cardiomyocytes isolated from defined regions
      of the rat left ventricle. All cardiomyocytes investigated (n=61) were positive
      for alpha-MHC and Kv4.2 expression. KChIP2 mRNA could also be detected in the
      vast majority (approximately 87%) of cardiomyocytes. Nearly all of these myocytes
      co-expressed all three cardiac splice variants of KChIP2. In a small but distinct
      fraction of myocytes (13%), however, we failed to detect KChIP2 mRNA. The
      detection thresholds were similar for all target genes and approached a
      sensitivity of a few molecules of RNA per cell. Our findings support the
      hypothesis that Itof is mediated by Kv4-KChIP2 heteromeric ion channels in the
      great majority of cardiac myocytes. A small subpopulation of cardiomyocytes,
      however, appears to express KChIP2 mRNA at insignificant levels and may therefore
      use other accessory subunits to generate Itof.

PMID- 15946676
TI  - Calcium transport in cardiovascular health and disease--the sarcolemmal calcium
      pump enters the stage.
AB  - Calcium is known to be one of the most important ionic regulators of the heart,
      where it has a crucial role in contraction-relaxation. Within a single beat of
      the cardiomyocyte there is a 100-fold increase in the cytosolic free Ca(2+)
      level, this must be returned to its original concentration in order to maintain
      the normal physiological function of the cell. Two of the mechanisms involved in
      returning the Ca(2+) concentration back to resting levels are located at the
      sarcolemma; the sodium/calcium exchanger (NCX) and the sarcolemmal calcium pump.
      Compared to the NCX the sarcolemmal calcium pump extrudes significantly less
      calcium from the cardiomyocyte and has long been thought to be involved in the
      maintenance of low diastolic calcium levels. This review will outline recent
      evidence suggesting that the sarcolemmal calcium pump may in fact play a key role
      in signal transduction in the cardiovascular system.

PMID- 15946677
TI  - Structural studies of human placental alkaline phosphatase in complex with
      functional ligands.
AB  - The activity of human placental alkaline phosphatase (PLAP) is downregulated by a
      number of effectors such as l-phenylalanine, an uncompetitive inhibitor, 5'-AMP,
      an antagonist of the effects of PLAP on fibroblast proliferation and by p
      nitrophenyl-phosphonate (PNPPate), a non-hydrolysable substrate analogue. For the
      first two, such regulation may be linked to its biological function that requires
      a reduced and better-regulated hydrolytic rate. To understand how such disparate
      ligands are able to inhibit the enzyme, we solved the structure of the complexes
      at 1.6A, 1.9A and 1.9A resolution, respectively. These crystal structures are the
      first of an alkaline phosphatase in complex with organic inhibitors. Of the three
      inhibitors, only l-Phe and PNPPate bind at the active site hydrophobic pocket,
      providing structural data on the uncompetitive inhibition process. In contrast,
      all three ligands interact at a remote peripheral site located 28A from the
      active site. In order to extend these observations to the other members of the
      human alkaline phosphatase family, we have modelled the structures of the other
      human isozymes and compared them to PLAP. This comparison highlights the crucial
      role played by position 429 at the active site in the modulation of the catalytic
      process, and suggests that the peripheral binding site may be involved in the
      functional specialization of the PLAP isozyme.

PMID- 15946678
TI  - CD4 binding partially locks the bridging sheet in gp120 but leaves the beta2/3
      strands flexible.
AB  - The structure of the free form HIV gp120, critical for therapeutic agent
      development, is unavailable due to its high flexibility. Previous thermodynamic
      data, structural analysis and simulation results have suggested a large
      conformational change in the core domain upon CD4 binding. The bridging sheet,
      which consists of four beta-strands with beta20/21 nestling against the
      inner/outer domains and beta2/3 facing outward, more exposed to the solvent, was
      proposed to be unfolded in the native state. In order to test this proposition
      and to characterize the native conformations, we performed potential mean force
      (PMF) molecular dynamics (MD) simulations on the CD4-bound crystal structure. We
      pushed the bridging sheet away from the inner and outer domain to explore the
      accessible conformational space for the bridging sheet. In addition, we performed
      conventional MD simulations on structures with the bridging sheet partially
      unfolded to investigate the stability of the association between the inner and
      outer domains. Based on the free energy profiles, we find that the whole bridging
      sheet is unlikely to unfold without other concurrent conformational changes. On
      the other hand, the partial bridging sheet, beta strands 2/3, can switch its
      conformation from the folded to the unfolded state. Furthermore, relaxation of
      conformation with partially unfolded bridging sheet through MD simulations leads
      to a conformation with beta strands 20/21 quickly re-anchoring against the inner
      and outer domains. Such a conformation, although lacking some of the hydrophobic
      interactions present in the CD4-bound structure, displayed high stability as
      further indicated by other restrained MD simulations. The relevance of this
      conformation to the free form structure and the pathway for conformational change
      from the free form to the CD4-bound structure is discussed in detail in light of
      the available unliganded SIV gp120 crystal structure.

PMID- 15946679
TI  - Conservation of Palindromic and Mirror Motifs within Inverted Terminal Repeats of
      mariner-like Elements.
AB  - The transposase of the mariner-like elements (MLEs) specifically binds as a dimer
      to the inverted terminal repeat of the transposon that encodes it. Two binding
      motifs located within the inverted terminal sequences (ITR) are therefore
      recognized, as previously indicated, by biochemical data obtained with the Mos1
      and Himar1 transposases. Here, we define the motifs that are involved in the
      binding of a MLE transposase to its ITR by analyzing the nucleic acid properties
      of the 5' and 3' ITR sequences from 45 MLEs, taking into account the fact that
      the transposase binds to the ITR, using its CRO binding domains and the general
      characteristics of the cro binding sites so far investigated. Our findings show
      that in all the MLE ITRs, the outer half was better conserved than the inner
      half. More interestingly, they allowed us to characterize conserved palindromic
      and mirror motifs specific to each "MLE species". The presence of the palindromic
      motifs was correlated to the binding of the transposase dimer, whereas the
      properties of the mirror motifs were shown to be responsible for the bend in each
      ITR that helps to stabilize transposase-ITR interactions.

PMID- 15946680
TI  - Functional cartography of the ectodomain of the type I interferon receptor
      subunit ifnar1.
AB  - Ligand-induced cross-linking of the type I interferon (IFN) receptor subunits
      ifnar1 and ifnar2 induces a pleiotrophic cellular response. Several studies have
      suggested differential signal activation by flexible recruitment of the accessory
      receptor subunit ifnar1. We have characterized the roles of the four Ig-like sub
      domains (SDs) of the extracellular domain of ifnar1 (ifnar1-EC) for ligand
      recognition and receptor assembling. Various sub-fragments of ifnar1-EC were
      expressed in insect cells and purified to homogeneity. Solid phase binding assays
      with the ligands IFN(alpha)2 and IFN(beta) revealed that all three N-terminal SDs
      were required and sufficient for ligand binding, and that IFN(alpha)2 and
      IFN(beta) compete for this binding site. Cellular binding assays with different
      fragments, however, highlighted the key role of the membrane-proximal SD for the
      formation of an in situ IFN-receptor complex. Even substitution with the
      corresponding SD from homologous cytokine receptors did not restore high-affinity
      ligand binding. Receptor assembling analysis on supported lipid bilayers in vitro
      revealed that the membrane-proximal SD controls appropriate orientation of the
      receptor on the membrane, which is required for efficient association of ifnar1
      into the ternary complex.

PMID- 15946681
TI  - Hydroxyl groups in the (beta)beta sandwich of metallo-beta-lactamases favor
      enzyme activity: a computational protein design study.
AB  - Metallo-beta-lactamases challenge antimicrobial therapies by their ability to
      hydrolyze and inactivate a broad spectrum of beta-lactam antibiotics. The
      potential of these enzymes to acquire enhanced catalytic efficiency through
      mutation is of great concern. Here, we explore the potential of computational
      protein design to predict mutants of the imipenemase IMP-1 that modulate the
      catalytic efficiency of the enzyme against a range of substrates. Focusing on the
      four amino acid positions 69, 121, 218, and 262, we carried out a number of
      design calculations. Two mutant enzymes were predicted: the single mutant S262A
      and the double mutant F218Y-S262A. Compared to IMP-1, the single mutant (S262A)
      results in the loss of a hydroxyl group and the double mutant (F218Y-S262A)
      results in a hydroxyl transfer from position 262 to position 218. The presence of
      both hydroxyl groups at positions 218 and 262 was tested by examining the mutant
      F218Y. Kinetic constants of IMP-1, the two computationally designed mutants
      (S262A and F218Y-S262A), and the hydroxyl addition mutant (F218Y) were determined
      with seven substrates. Catalytic efficiencies are highest for the enzyme with
      both hydroxyl groups (F218Y) and lowest for the enzyme lacking both hydroxyl
      groups (S262A). The catalytic efficiencies of the two enzymes with one hydroxyl
      group each are intermediate, with the F218Y-S262A double mutant exhibiting
      enhanced hydrolysis of nitrocefin, cephalothin, and cefotaxime relative to IMP-1.

PMID- 15946682
TI  - Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and
      the structural basis of disease-causing mutations.
AB  - Human dihydrolipoamide dehydrogenase (hE3) is an enzymatic component common to
      the mitochondrial alpha-ketoacid dehydrogenase and glycine decarboxylase
      complexes. Mutations to this homodimeric flavoprotein cause the often-fatal human
      disease known as E3 deficiency. To catalyze the oxidation of dihydrolipoamide,
      hE3 uses two molecules: non-covalently bound FAD and a transiently bound
      substrate, NAD+. To address the catalytic mechanism of hE3 and the structural
      basis for E3 deficiency, the crystal structures of hE3 in the presence of NAD+ or
      NADH have been determined at resolutions of 2.5A and 2.1A, respectively. Although
      the overall fold of the enzyme is similar to that of yeast E3, these two
      structures differ at two loops that protrude from the proteins and at their FAD
      binding sites. The structure of oxidized hE3 with NAD+ bound demonstrates that
      the nicotinamide moiety is not proximal to the FAD. When NADH is present,
      however, the nicotinamide base stacks directly on the isoalloxazine ring system
      of the FAD. This is the first time that this mechanistically requisite
      conformation of NAD+ or NADH has been observed in E3 from any species. Because E3
      structures were previously available only from unicellular organisms,
      speculations regarding the molecular mechanisms of E3 deficiency were based on
      homology models. The current hE3 structures show directly that the disease
      causing mutations occur at three locations in the human enzyme: the dimer
      interface, the active site, and the FAD and NAD(+)-binding sites. The mechanisms
      by which these mutations impede the function of hE3 are discussed.

PMID- 15946683
TI  - A snapshot of viral evolution from genome analysis of the tectiviridae family.
AB  - The origin, evolution and relationships of viruses are all fascinating topics.
      Current thinking in these areas is strongly influenced by the tailed double
      stranded (ds) DNA bacteriophages. These viruses have mosaic genomes produced by
      genetic exchange and so new natural isolates are quite dissimilar to each other,
      and to laboratory strains. Consequently, they are not amenable to study by
      current tools for phylogenetic analysis. Less attention has been paid to the
      Tectiviridae family, which embraces icosahedral dsDNA bacterial viruses with an
      internal lipid membrane. It includes viruses, such as PRD1, that infect Gram
      negative bacteria, as well as viruses like Bam35 with Gram-positive hosts.
      Although PRD1 and Bam35 have closely related virion morphology and genome
      organization, they have no detectable sequence similarity. There is strong
      evidence that the Bam35 coat protein has the "double-barrel trimer" arrangement
      of PRD1 that was first observed in adenovirus and is predicted to occur in other
      viruses with large facets. It is very likely that a single ancestral virus gave
      rise to this very large group of viruses. The unprecedented degree of
      conservation recently observed for two Bam35-like tectiviruses made it important
      to investigate those infecting Gram-negative bacteria. The DNA sequences for six
      PRD1-like isolates (PRD1, PR3, PR4, PR5, L17, PR772) have now been determined.
      Remarkably, these bacteriophages, isolated at distinctly different dates and
      global locations, have almost identical genomes. The discovery of almost
      invariant genomes for the two main Tectiviridae groups contrasts sharply with the
      situation in the tailed dsDNA bacteriophages. Notably, it permits a sequence
      analysis of the isolates revealing that the tectiviral proteins can be dissected
      into a slowly evolving group descended from the ancestor, the viral self, and a
      more rapidly changing group reflecting interactions with the host.

PMID- 15946684
TI  - Correlated evolutionary pressure at interacting transcription factors and DNA
      response elements can guide the rational engineering of DNA binding specificity.
AB  - Understanding the molecular mechanisms of the specific interaction between
      transcription factor proteins and DNA is key to comprehend the regulation of gene
      expression and to develop technologies to engineer transcription factors. Thus
      far, although there have been several attempts to elucidate protein-DNA
      interaction through amino acid-base recognition codes, sequence based profiles,
      or physical models of interaction, the greatest successes in engineering DNA
      binding specificity remain experimental. Here we present the first systematic
      evidence of correlated evolutionary pressure at interacting amino acid residues
      and DNA base-pairs in transcription factors, and show that it can be used to
      rationally engineer DNA binding specificity. The correlation is between the
      relative evolutionary importance of protein residues and DNA bases, measured,
      respectively, in terms of the Evolutionary Trace (ET) rank and information
      entropy. The evolutionarily most important residues interact with the most
      conserved base-pairs within the response element while residues of least
      importance interact with the most variable base-pairs. The correlation averages
      0.74 over 12 unrelated families of transcriptional regulators, including nuclear
      hormone receptors, basic helix-loop-helix, ETS- and homeo-domain family. To test
      the predictive power of this correlation, we targeted a mutational swap of top
      ranked ET residues in a transcription factor, LRH-1. This redirects LRH-1 binding
      as predicted and showed that, in this case, evolutionary importance and binding
      specificity are coupled sufficiently strongly for the Evolutionary Trace to guide
      the computational design of DNA binding specificity. This establishes the
      existence of evolutionary importance correlation at protein-DNA interfaces, and
      demonstrates that it is a useful principle for the rational engineering of
      binding specificity.

PMID- 15946685
TI  - Improvement of occipital alpha activity by repetitive hyperbaric oxygen therapy
      in patients with carbon monoxide poisoning: a possible indicator for treatment
      efficacy.
AB  - OBJECTIVES: The main aim of this study was to evaluate the efficacy of repetitive
      hyperbaric oxygen (HBO) treatments with monitoring of quantitative
      electroencephalography (qEEG) for symptoms of acute carbon monoxide (CO)
      poisoning and prevention of delayed neuropsychiatric sequelae. METHODS: Eight
      patients with acute CO poisoning received repetitive HBO treatments five times a
      week and qEEG was recorded once a week. Peak alpha frequency, peak alpha power,
      and absolute and relative alpha power in the occipital region were evaluated. The
      repetitive HBO treatments were discontinued when the peak alpha frequency
      increased to and maintained a maximum in each patient. RESULTS: The mean number
      of HBO treatments was 20.3. The peak alpha frequency and the relative alpha power
      significantly increased after repetitive HBO treatments. The absolute alpha power
      and the peak alpha power insignificantly improved. Total numbers of HBO
      treatments were not correlated with age, duration of CO exposure, initial level
      of COHb, or interval to the first HBO treatment. After the completion of
      repetitive HBO treatments, no patient developed delayed neuropsychiatric
      sequelae. CONCLUSIONS: These results suggest that repetitive HBO treatments may
      prevent the delayed neuropsychiatric sequelae of CO poisoning when applied
      individually with monitoring of the peak alpha frequency as an indicator of
      efficacy.

PMID- 15946686
TI  - Corticosteroids treatment of multiple sclerosis.

PMID- 15946687
TI  - Middle cerebral artery dissections: differences between isolated and extended
      dissections of internal carotid artery.
AB  - Isolated middle cerebral artery dissection (MCAD) has rarely been encountered
      clinically and few have reviewed it systemically. The etiologies, clinical
      manifestations, natural clinical course and prognosis of MCAD remain poorly
      understood. From 1995 to 2004, there were 5 cases diagnosed clinically and
      angiographically to have MCAD (isolated MCAD in 1, ICAD-MCAD in 4) from a medical
      center in Taiwan. MEDLINE (1966-2003) was searched for published articles in
      English that concerned the diagnosis of MCAD. Clinical presentations, stroke
      types, angiographic findings, etiologies, treatment strategies and outcomes were
      compared between cases with isolated MCAD or ICAD-MCAD. There were 23 cases
      (male, 46%; mean age, 22.9+/-19.5 years) with 24 events of isolated MCAD and 31
      cases (male, 47%; mean age, 22.2+/-12.9 years) with 35 events of ICAD-MCAD. The
      types of stroke in isolated MCAD group included subarachnoid hemorrhage (12%) and
      cerebral infarction (88%); and in ICAD-MCAD group were subarachnoid hemorrhage
      (6%) and cerebral infarction (94%). The presenting symptoms were similar between
      both groups. Fluctuating course was more often in isolated MCAD than in ICAD-MCAD
      (17% vs. 3%, p=0.061). Recurrence of dissection events in both groups was
      infrequent (4% vs. 9%, p=0.56). Both groups had high case-fatality rates (MCAD,
      48%; ICAD-MCAD, 58%). The cause of dissection in both groups was idiopathic in
      the majority. Congenital vessel wall defects were found in 26% of ICAD-MCAD, but
      in only 4% of isolated MCAD (p=0.066). In contrast, preceded trauma was more
      often found in isolated MCAD than ICAD-MCAD (35% vs. 19%, p=0.085). Arteritis was
      noted in 16% of ICAD-MCAD patients, but none in isolated MCAD. Angiography
      revealed segmental stenosis in 72% of isolated MCAD and 96% of ICAD-MCAD.
      Aneurysmal dilatation of the involved cerebral arteries was noted in 28% of
      isolated MCAD, but none in MCAD-ICAD. Both isolated MCAD and ICAD-MCAD can cause
      vascular events with high mortality rates. Several aspects differed between 2
      groups, including clinical course, underlying etiologies and angiographic
      findings.

PMID- 15946688
TI  - Aberrant accentuation of neurofibrillary degeneration in the hippocampus of
      Alzheimer's disease with amyloid precursor protein 717 and presenilin-1 gene
      mutations.
AB  - This study reports correlation of the hippocampal neurofibrillary tangles (NFT)
      density with beta-amyloid (Abeta) precursor protein (APP) 717 mutation,
      presenilin (PS)-1 mutation and apolipoprotein E (Apo-E) e4 alleles (E4), being
      graded as 3 forms (no-E4, one-E4 and two-E4) in autopsied brains from patients
      with familial and non-familial Alzheimer's disease (AD). We studied the density
      of NFT-free neurons, intracellular NFT (I-NFT), extracellular NFT (E-NFT) and
      total NFT (I-NFT plus E-NFT) in the six hippocampal subdivisions: cornu ammonis
      (CA) 1-CA4, subiculum and entorhinal cortex. The APP mutation cases showed
      significantly higher total NFT density in the CA1-CA2 region, and the PS-1
      mutation cases also showed higher density of total NFT in the CA1-CA3 than non
      familial cases. Moreover, high densities of the E-NFT contributed to these high
      total NFT densities. Non-familial AD cases showed a stereotypical NFT
      distribution with entorhinal accentuation in the hippocampus irrespective of E4
      frequency. Thus, APP and PS-1 mutations predominantly affect the CA regions with
      profound neurodegeneration, which contributes early and severe clinical features
      of familial AD.

PMID- 15946689
TI  - Low-frequency transcranial magnetic stimulation for epilepsia partialis continua
      due to cortical dysplasia.
AB  - The potential therapeutic role of repetitive transcranial magnetic stimulation
      (rTMS) in epilepsy has been increasingly recognized. We investigated the effects
      of low-frequency rTMS in a patient with epilepsia partialis continua (EPC) due to
      cortical dysplasia. A 31-year-old female patient experienced EPC in the right
      upper and lower extremities, which had lasted for 15 years without generalized
      seizures. MRI showed focal megaencephaly around the motor cortex suggestive of
      cortical dysplasia. A figure of eight magnetic coil was placed over the hand
      motor area, and 100 stimuli with an intensity at 90% of motor threshold were
      given at 0.5 Hz. Immediately after rTMS, EPC was nearly abolished. The effects
      had continued approximately for 2 months, and the second trial resulted in the
      similar effects and time-course. Low-frequency rTMS was safe and well tolerated
      in this patient. These findings support the concept that rTMS decreases cortical
      excitability, and may be an effective treatment for focal partial seizures.

PMID- 15946690
TI  - Multiple sclerosis in Iraq: does it have the same features encountered in Western
      countries?
AB  - OBJECTIVES: To characterize the clinical, demographic and epidemiological
      features of MS patients from the only specialised MS centre in Iraq. METHODS:
      Data for consecutive Iraqi MS patients attending the Baghdad Multidiscipline MS
      Clinic between 2000 and 2002 who fulfilled Poser et al. criteria for clinically
      definite (CD) and clinically probable (CP) MS were reviewed. RESULTS: We
      identified a total of 300 MS patients (164 females, 54.7%; 136 males, 45.3%) with
      a mean age of onset being 29.2+/-7.8 years and the duration being 8.6+/-5.9
      years. According to the year of clinical onset of MS, a progressive increase in
      cases in the last two decades and a trend towards more females was noted. Initial
      symptom was reported as motor in 31.7%, sensory in 28.3%, optic nerve in 24% and
      brainstem or cerebellar in 22.3% of patients. The course was relapsing-remitting
      in 199 (66.3%) patients, secondary progressive in 56 (18.7%) and primary
      progressive (PP) in 45 (15%) patients. CONCLUSIONS: MS is not rare in Iraq; its
      demographic and clinical data were, in general, similar to those reported in
      Caucasian populations. There was some evidence for North-South gradient and a
      possible increasing incidence characterized by an increase in female
      preponderance during the last 2 decades.

PMID- 15946691
TI  - Protective effect of Capparis spinosa on chondrocytes.
AB  - The aim of the present study was to evaluate the in vitro chondroprotective
      effects of the lyophilised methanolic extract from flowering buds of Capparis
      Spinosa L (LECS). This plant, common to the Mediterranean basin, has been used by
      the traditional medicine for its diuretic and antihypertensive effects and also
      in certain pathological conditions related to uncontrolled lipid peroxidation.
      The extract contains many constituents, in particular some flavonoids (kaempferol
      and quercetin derivatives) and hydrocinammic acids with several known biological
      effects such as the anti-inflammatory and the antioxidant ones. In this study, we
      assayed the effect of LECS on human chondrocytes cultures stimulated by
      proinflammatory cytokine interleukin-1beta (IL-1beta) and we determined the
      production of key molecules released during chronic inflammatory events (nitric
      oxide, glycosaminoglycans, prostaglandins and reactive oxygen species). We
      observed that LECS was able to counteract the harmful effects induced by IL
      1beta. This protection appeared to be greater than that elicited by indomethacin,
      which is usually employed in joint diseases. Since LECS possess a
      chondroprotective effect, it might be used in the management of cartilage damage
      during the inflammatory processes.

PMID- 15946692
TI  - Sulindac activates nuclear translocation of AIF, DFF40 and endonuclease G but not
      induces oligonucleosomal DNA fragmentation in HT-29 cells.
AB  - Sulindac is one of the most widely studied nonsteroidal anti-inflammatory drugs
      in the prevention of colon cancer. Thus, from the viewpoint of colon cancer
      chemotherapy it is important to reveal the mechanism of sulindac-induced cell
      death. This study was undertaken to dissect the molecular mechanism underlying
      sulindac-induced apoptosis in human colon cancer cell line HT-29 (mutant p53),
      focusing on nuclear translocation of AIF, DFF and endonuclease G. On induction of
      apoptosis by sulindac, it was associated with decreased mitochondrial membrane
      potential, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose)
      polymerase, translocation of mitochondrial proteins to the nucleus, and
      morphological evidence of nuclear condensation. However, sulindac led to only
      disintegration of nuclear DNA into high molecular weight DNA fragments of about
      100-300 kbp as determined by a pulse-field gel electrophoresis, suggesting a
      predominantly AIF-mediated cell death process. In summary, our findings indicate
      that sulindac induces large-scale DNA fragmentation without oligonucleosomal DNA
      fragmentation. This result suggests that nuclear translocation of DFF and
      endonuclease G are not sufficient for the induction of oligonucleosomal DNA
      fragmentation in HT-29 cells.

PMID- 15946693
TI  - Expression of nuclear hormone receptors, their coregulators and type I
      iodothyronine 5'-deiodinase gene in mammary tissue of nonlactating and
      postlactating rats.
AB  - The aim of the study was to test the hypothesis that expression of retinoid
      receptors (RARalpha, RARbeta, RARgamma), rexinoid receptors (RXRalpha, RXRbeta),
      thyroid hormone receptors (TRalpha, TRbeta), estrogen receptors (ERalpha,
      ERbeta), nuclear receptor coregulators (N-CoR, SRC-1, SMRT), and in addition type
      I iodothyronine 5'-deiodinase (5'-DI), EGFR and erb-B2/neu would be different in
      mammary postlactating tissue in comparison with that of nonlactating mammary
      gland. Using RT-PCR, we have shown that expression of RARalpha, RXRalpha,TRalpha,
      ERalpha,ERbeta,N-CoR, SRC-1, SMRT and EGFR in rat was significantly increased in
      postlactating mammary gland when compared to that of nonlactating mammary tissue.
      Postlactating mammary glands were found to express all RAR and RXR subtypes
      studied when compared to nonlactating mammary tissues that express exclusively
      RARalpha and RXRalpha subtypes. Enhanced expression of a number of nuclear
      hormone receptors, their coregulators in mammary tissue of postlactating rats in
      comparison with nonlactating animals identify a potential role for retinoid,
      thyroid and estrogen signalling pathways also after lactation period.

PMID- 15946694
TI  - Treatment for psychological dependence on morphine: usefulness of inhibiting NMDA
      receptor and its associated protein kinase in the nucleus accumbens.
AB  - A growing body of evidence indicates that the mesolimbic dopaminergic (DAergic)
      pathway projecting from the ventral tegmental area (VTA) to the nucleus accumbens
      (N.Acc.) play a critical role in the initiation of psychological dependence on
      morphine. As well as DAergic system, the involvement of non-DAergic
      neurotransmitter and neuromodulator systems in rewarding effects induced by
      morphine has been recently documented. We previously demonstrated that the
      morphine-induced rewarding effect was dramatically suppressed by co-treatment
      with NMDA receptor antagonists, such as dizocilpine (MK-801), ketamine and
      ifenprodil. Therefore, we propose here that inhibiting the N-methyl-D-aspartate
      (NMDA) receptor and its associated protein kinase in the N.Acc. is useful for the
      treatment for psychological dependence on morphine. The following review provides
      a summary of recent our findings regarding the role of NMDA receptor and its
      associated protein kinase in the development of psychological dependence on
      morphine.

PMID- 15946695
TI  - ANG II increases 2-deoxyglucose uptake in mouse embryonic stem cells.
AB  - It is now suggested that all components of the renin-angiotensin system are
      present in many tissues, including the embryo and may play a major role in embryo
      development and differentiation. However, little is known regarding whether ANG
      II regulates glucose transport in mouse embryonic stem (ES) cells. Thus, the
      effects of ANG II on [3H]-2-deoxyglucose (2-DG) uptake and its related signal
      pathways were examined in mouse ES cells. ANG II significantly increased cell
      proliferation and 2-DG uptake in concentration- and time-dependent manner (>18 h,
      >10(-8) M) and increased mRNA and protein level of GLUT1 by 31+/-7% and 22+/-5%
      compared to control, respectively. Actinomycin D and cycloheximide completely
      blocked the effect of ANG II on 2-DG uptake. ANG II-induced increase of 2-DG
      uptake was blocked by losartan, an ANG II type 1 (AT1) receptor blocker, but not
      by PD 123319, an ANG II type 2 (AT2) receptor blocker. In addition, ANG II
      induced stimulation of 2-DG uptake was attenuated by phospholipase C (PLC)
      inhibitors, neomycin and U 73122 and ANG II increased inositol phosphates (IPs)
      formation by 37+/-8% of control. Protein kinase C (PKC) inhibitors,
      staurosporine, bisindolylmaleimide I, and H-7 also blocked ANG II-induced
      stimulation of 2-DG uptake. Indeed, ANG II activated a PKC translocation from the
      cytosolic to membrane fraction, suggesting a role of PKC. A 23187 (Ca2+
      ionophore) increased 2-DG uptake and nifedifine (L-type Ca2+ channel blocker)
      blocked it. In conclusion, ANG II increased 2-DG uptake by PKC activation via AT1
      receptor in mouse ES cells.

PMID- 15946696
TI  - Nicotine affects mineralized nodule formation by the human osteosarcoma cell line
      Saos-2.
AB  - Several in vitro and in vivo studies have indicated that tobacco smoking may be
      an important risk factor for the development and severity of inflammatory
      periodontal disease. In the present study, we examined the effect of nicotine on
      cell proliferation, alkaline phosphatase (ALPase) activity, mineralized nodule
      formation, and the expression of extracellular matrix proteins in the human
      osteosarcoma cell line Saos-2. The cells were cultured with Dulbecco's modified
      Eagle medium containing 10% fetal bovine serum with 0, 10(-4) M, and 10(-3) M
      nicotine for up to 14 days. Mineralized nodule formation was examined by alizarin
      red staining, and the calcium content in mineralized nodules was determined using
      a calcium E-test kit. The expression of extracellular matrix proteins was
      estimated by determining the levels of their mRNAs using the real-time polymerase
      chain reaction. Mineralized nodule formation and calcium content in mineralized
      nodules were remarkably suppressed by nicotine on days 10 and 14 of culture,
      respectively. ALPase activity as well as type I collagen and osteopontin
      expression also decreased in the presence of nicotine after 5, 10, and 14 days of
      culture, respectively. By contrast, the amount of bone sialoprotein increased
      during 14 days of culture with nicotine. These results suggest that nicotine
      suppresses osteogenesis through a decrease in ALPase and type I collagen
      production by osteoblasts.

PMID- 15946697
TI  - Nitric oxide, ceramide and sphingomyelinase-coupled receptors: a tale of enzymes
      and messengers coordinating cell death, survival and differentiation.
AB  - The gaseous messenger nitric oxide plays a role in a variety of biological
      functions. Evidence accumulated over the last 7 years indicates that functions of
      nitric oxide in apoptosis growth and differentiation may originate in part from
      an interplay with signalling members of the sphingolipid family. Interactions
      between nitric oxide and sphingolipids have been shown to be multiple, to involve
      regulation of activity and expression of the enzymes responsible for the
      synthesis of nitric oxide and of those involved in the sphingolipid metabolic
      pathways. Recent evidence indicates that one of these interactions, namely the
      cross-talk of sphingomyelinases and their product ceramide with nitric oxide and
      its generating enzyme endothelial nitric oxide synthase, plays prominent roles
      during key patho-physiological processes such as inflammation, proliferation,
      death and differentiation.

PMID- 15946698
TI  - Evidence that the species barrier of human immunodeficiency virus-1 does not
      extend to uptake by the blood--brain barrier: comparison of mouse and human brain
      microvessels.
AB  - HIV-1 within the CNS produces a neuroAIDS syndrome and may act as a reservoir for
      reinfection of the peripheral tissues. Study of how HIV-1 crosses the blood-brain
      barrier (BBB) has been hampered by the lack of nonprimate animal models. However,
      BBB transport of HIV-1 does not involve any of the known steps conferring species
      specificity, including binding to CD4 receptors. In vivo and in vitro studies
      show that HIV-1 and its glycoprotein coat, gp120, are taken up and transported
      across the BBB of the mouse. Here, we compared the ability of gp120 and HIV-1 to
      be taken up by isolated brain microvessels (IBM) freshly isolated from mice, from
      post-mortem human brain, and from mice that had been treated in a manner
      analogous to the human material (mouse post-mortem). Freshly isolated mouse IBM
      took up more gp120 and HIV-1 than the human or mouse post-mortem cells. We found
      no difference between the ability of mouse post-mortem and human IBM to take up
      either gp120 or HIV-1. Wheatgerm agglutinin has been previously shown to
      stimulate gp120 and HIV-1 uptake by the BBB; here, it stimulated the uptake of
      gp120 and of HIV-1 by both mouse post-mortem and human IBM, although stimulated
      uptake was greatest for fresh mouse IBM. These results show that the mouse can be
      used to study the initial phases of HIV-1 uptake by the BBB.

PMID- 15946699
TI  - Lipids and drugs of abuse.
AB  - Drug abuse continues to take an enormous economic and social toll on the world.
      Among the costs are reduced productivity, increased need for medical services and
      stress on families. Treatments that allow affected individuals to reduce
      compulsive drug use are lacking and novel approaches to their development will
      likely come from increased understanding of the consequences of chronic exposure
      to reinforcing drugs. The purpose of this review is to explore the role of lipids
      in drug abuse and to present a rationale for an increased focus on the
      interactions between drugs of abuse and lipids in the brain. Small molecular
      weight lipids function as neuromodulators in the brain and, as such, play a role
      in the synaptic plasticity that occurs following exposure to drugs of abuse. In
      addition, the membrane lipid bilayer consists of lipid subdomains and emerging
      evidence suggests that protein function can be altered by transient associations
      with these subdomains. Finally, lipidomics is a very new field devoted to the
      exploration of changes in cellular lipid constituents during phenotypic
      alterations. Enhanced research in all of these areas will likely provide useful
      insights into and, perhaps, therapeutic targets for the treatment of drug abuse.

PMID- 15946700
TI  - Evaluation of the Mytilus galloprovincialis Lam. digestive gland metallothionein
      as a biomarker in a long-term field study: seasonal and spatial variability.
AB  - A study was made of seasonal and spatial variability of metallothionein (MT)
      concentrations, determined spectrophotometrically in the soluble fraction of the
      digestive gland of mussels Mytilus galloprovincialis, collected between 1999 and
      2001 from several coastal and estuarine locations along the central Eastern
      Adriatic coast (Croatia). The seasonal influence on the MT and metal
      concentrations (higher values in winter-spring season, than in summer-autumn
      season) is more pronounced than the local site-specific influence. Furthermore,
      within each season a significant site-specific dependence on the MT and trace
      metal variations can be detected. An inverse relationship of mussel condition
      index (CI) and temperature with MT and trace metals levels indicates the
      influence of food abundance and mussel annual reproductive cycle. Substantially
      higher concentrations of both MT and Cd were recorded in mussels inhabiting
      estuarine locations, possibly indicating a markedly higher Cd bioavailability at
      these locations. The positive correlations obtained between MT and Cd in all
      seasons except autumn support an argument for application of digestive gland MT
      as a biomarker of Cd exposure, providing evidence for assessing the most
      appropriate season for mussel sampling.

PMID- 15946701
TI  - Significance of cytochrome P450 system responses and levels of bile fluorescent
      aromatic compounds in marine wildlife following oil spills.
AB  - The relationships among cytochrome P450 induction in marine wildlife species,
      levels of fluorescent aromatic compounds (FAC) in their bile, the chemical
      composition of the inducing compounds, the significance of the exposure pathway,
      and any resulting injury, as a consequence of exposure to crude oil following a
      spill, are reviewed. Fish collected after oil spills often show increases in
      cytochrome P450 system activity, cytochrome P4501A (CYP1A) and bile fluorescent
      aromatic compounds (FAC), that are correlated with exposure to polycyclic
      aromatic hydrocarbons (PAH) in the oil. There is also some evidence for increases
      in bile FAC and induction of cytochrome P450 in marine birds and mammals after
      oil spills. However, when observed, increases in these exposure indicators are
      transitory and generally decrease to background levels within one year after the
      exposure. Laboratory studies have shown induction of cytochrome P450 systems
      occurs after exposure of fish to crude oil in water, sediment or food. Most of
      the PAH found in crude oil (dominantly 2- and 3-ring PAH) are not strong inducers
      of cytochrome P450. Exposure to the 4-ring chrysenes or the photooxidized
      products of the PAH may account for the cytochrome P450 responses in fish
      collected from oil-spill sites. The contribution of non-spill background PAH,
      particularly combustion-derived (pyrogenic) PAH, to bile FAC and cytochrome P450
      system responses can be confounding and needs to be considered when evaluating
      oil spill effects. The ubiquity of pyrogenic PAH makes it important to fully
      characterize all sources of PAH, including PAH from natural resources, e.g.
      retene, in oil spill studies. In addition, such parameters as species, sex, age,
      ambient temperature and season need to be taken into account. While increases in
      fish bile FAC and cytochrome P450 system responses, can together, be sensitive
      general indicators of PAH exposure after an oil spill, there is little
      unequivocal evidence to suggest a linkage to higher order biological effects,
      e.g. toxicity, lesions, reproductive failure.

PMID- 15946702
TI  - Clionid sponge surveys on the Florida Reef Tract suggest land-based nutrient
      inputs.
AB  - Bioerosion by Cliona delitrix and Cliona lampa was assessed at 43 sites along the
      Florida Reef Tract, USA, in the summer of 2001. Sponge abundances were estimated
      using rapid visual assessment. Tissue samples of sponges were taken for analysis
      of delta15N. Comparison samples were taken from Belize. Annual trends in sponge
      abundance were estimated from archived videos covering the period from 1996 to
      2001. Sites with the greatest boring sponge size and cover were in the
      Backcountry and Lower Keys, where total nitrogen, ammonium, and delta15N levels
      were highest. The sites with the largest relative increase of C. delitrix and C.
      lampa over the 5 year period were in the Upper Keys, where the greatest relative
      decline in stony coral cover has occurred. Florida sponge delta15N values were
      5.2(+/-0.1)%, suggesting the influence of human waste; in comparison, offshore
      Belize samples were 2.1(+/-0.1)%. These results suggest sewage contamination of
      the Florida Reef Tract, shifting the carbonate balance from construction to
      destruction.

PMID- 15946703
TI  - A procedure for identifying significant environmental aspects in sea ports.
AB  - A new methodology has been designed to identify and rank the significant
      environmental aspects in sea ports. The main objective of the Strategic Overview
      of Significant Environmental Aspects (SOSEA) is to help port managers to identify
      significant environmental aspects and to reinforce the awareness about them in
      order to prioritise work in environmental management. Developed in close
      collaboration with port environmental managers and tested in a set of ports, it
      is a user-friendly tool that can be applied in approximately half a working day.
      It is based on ISO 14001 vocabulary and requirements and it can be considered as
      the base for the implementation of any Environmental Management System for port
      communities.

PMID- 15946704
TI  - Increased phagocytic activity in contaminated seastars (Asterias rubens)
      collected in the Southern Bight of the North Sea.
AB  - In invertebrates, the phagocytosis exerted by immune cells constitutes the main
      line of internal defence against offending microorganisms. This study assessed
      during two consecutive years the phagocytic activity in seastars (Asterias
      rubens) collected in stations along the Belgian and Dutch coasts. The
      contamination of these seastars by metals and PCBs were measured in parallel.
      Increased phagocytic activities were found in seastars collected in the plume of
      the Scheldt river. This correlated with the contamination of seastars by metals,
      mainly Pb, but not with the contamination by the analysed PCB congeners.
      Furthermore, the relationship between phagocytosis and metal contamination was
      reproducible from one year to another. The possible mechanisms explaining this
      effect are discussed in light of a direct or indirect link between phagocytic
      activity and metal contamination of seastars.

PMID- 15946705
TI  - Overseas garbage pollution on beaches of northeast Brazil.

PMID- 15946706
TI  - Disseminated neoplasia in blue mussels, Mytilus galloprovincialis, from the Black
      Sea, Romania.
AB  - Disseminated neoplasia, also called leukemia or hemic neoplasia, has been
      detected in 15 species of marine bivalve mollusks worldwide. The disease is
      characterized by the presence of single anaplastic cells with enlarged nuclei and
      sometimes frequent mitosis, in hemolymph vessels and sinuses. The neoplastic
      cells gradually replace normal hemocytes leading to the increased mortality of
      animals. The neoplasia reaches epizootic prevalences in blue mussels, Mytilus
      trossulus, in some areas, whereas prevalences in Mytilus edulis are generally
      very low. Mytilus galloprovincialis was suggested to be resistant to the disease
      although very low prevalences were documented from Spain in the Atlantic Ocean
      and Italy in the Mediterranean Sea. A case of disseminated neoplasia was
      discovered in M. galloprovincialis from among 200 specimens studied from the
      coast of the Romanian Black Sea. Histological preparation revealed the presence
      of large anaplastic cells with lobed nuclei. This observation extends the
      geographic range of marine bivalve mollusks with disseminated neoplasia to
      include the Black Sea.

PMID- 15946707
TI  - Experimental investigation of various vegetable fibers as sorbent materials for
      oil spills.
AB  - Oil spills are a global concern due to their environmental and economical impact.
      Various commercial systems have been developed to control these spills, including
      the use of fibers as sorbents. This research investigates the use of various
      vegetable fibers, namely mixed leaves residues, mixed sawdust, sisal (Agave
      sisalana), coir fiber (Cocos nucifera), sponge-gourd (Luffa cylindrica) and silk
      floss as sorbent materials of crude oil. Sorption tests with crude oil were
      conducted in deionized and marine water media, with and without agitation. Water
      uptake by the fibers was investigated by tests in dry conditions and distillation
      of the impregnated sorbent. The silk-floss fiber showed a very high degree of
      hydrophobicity and oil sorption capacity of approximately 85goil/g sorbent (in
      24hours). Specific gravity measurements and buoyancy tests were also used to
      evaluate the suitability of these fibers for the intended application.

PMID- 15946708
TI  - Cancer self remission and tumor stability-- a stochastic approach.
AB  - The paper aims to express the spontaneous regression and progression of a
      malignant tumor system as a prey--predator like system. The model is a three
      dimensional deterministic system, consisting of tumor cells, hunting predator
      cells and resting predator cells. Local stability analysis is performed along
      with numerical simulations to support the analytical findings. Moreover, the
      deterministic model is extended to a stochastic one allowing random fluctuations
      around the positive interior equilibrium. The stochastic stability properties of
      the model are investigated both analytically and numerically. The thresholds
      obtained from our study may be helpful to control the malignant tumor growth.

PMID- 15946709
TI  - A comparison of persistence-time estimation for discrete and continuous
      stochastic population models that include demographic and environmental
      variability.
AB  - A discrete-time Markov chain model, a continuous-time Markov chain model, and a
      stochastic differential equation model are compared for a population experiencing
      demographic and environmental variability. It is assumed that the environment
      produces random changes in the per capita birth and death rates, which are
      independent from the inherent random (demographic) variations in the number of
      births and deaths for any time interval. An existence and uniqueness result is
      proved for the stochastic differential equation system. Similarities between the
      models are demonstrated analytically and computational results are provided to
      show that estimated persistence times for the three stochastic models are
      generally in good agreement when the models satisfy certain consistency
      conditions.

PMID- 15946710
TI  - Current advances in unraveling the function of the Werner syndrome protein.
AB  - Werner syndrome (WS) is an autosomal recessive premature aging disease manifested
      by the mimicry of age-related phenotypes such as atherosclerosis,
      arteriosclerosis, cataracts, osteoporosis, soft tissue calcification, premature
      thinning, graying, and loss of hair, as well as a high incidence of some types of
      cancers. The gene product defective in WS, WRN, is a member of the RecQ family of
      DNA helicases that are widely distributed in nature and believed to play central
      roles in genomic stability of organisms ranging from prokaryotes to mammals.
      Interestingly, WRN is a bifunctional protein that is exceptional among RecQ
      helicases in that it also harbors an exonuclease activity. Furthermore, it
      preferentially operates on aberrant DNA structures believed to exist in vivo as
      intermediates in specific DNA transactions such as replication (forked DNA),
      recombination (Holliday junction, triplex and tetraplex DNA), and repair (partial
      duplex with single stranded bubble). In addition, WRN has been shown to
      physically and functionally interact with a variety of DNA-processing proteins,
      including those that are involved in resolving alternative DNA structures, repair
      DNA damage, and provide checkpoints for genomic stability. Despite significant
      research activity and considerable progress in understanding the biochemical and
      molecular genetic function of WRN, the in vivo molecular pathway(s) of WRN remain
      elusive. The following review focuses on the recent advances in the biochemistry
      of WRN and considers the putative in vivo functions of WRN in light of its many
      protein partners.

PMID- 15946711
TI  - Lost in space--the fate of memory representations for non-neglected stimuli.
AB  - Typically, spatial neglect after right-hemisphere brain damage is defined as a
      failure to orient towards or attend to stimuli located towards the
      contralesional, in this case the left, side of space. Here, we report that
      neglect patients have difficulty maintaining the spatial locations of vertically
      arranged stimuli on the right side of space. This indicates that neglect is
      associated with a severe deficit in the maintenance of spatial information even
      on the ipsilesional "good" side.

PMID- 15946712
TI  - Floral benzenoid carboxyl methyltransferases: from in vitro to in planta
      function.
AB  - Benzenoid carboxyl methyltransferases synthesize methyl esters (e.g., methyl
      benzoate and methyl salicylate), which are constituents of aromas and scents of
      many plant species and play important roles in plant communication with the
      surrounding environment. Within the past five years, eleven such carboxyl
      methyltransferases were isolated and most of them were comprehensively
      investigated at the biochemical, molecular and structural level. Two types of
      enzymes can be distinguished according to their substrate preferences: the SAMT
      type enzymes isolated from Clarkia breweri, Stephanotis floribunda, Antirrhinum
      majus, Hoya carnosa, and Petunia hybrida, which have a higher catalytic
      efficiency and preference for salicylic acid, while BAMT-type enzymes from A.
      majus, Arabidopsis thaliana, Arabidopsis lyrata, and Nicotiana suaveolens prefer
      benzoic acid. The elucidation of C. breweri SAMT's three-dimensional structure
      allowed a detailed modelling of the active sites of the carboxyl
      methyltransferases and revealed that the SAM binding pocket is highly conserved
      among these enzymes while the methyl acceptor binding site exhibits some
      variability, allowing a classification into SAMT-type and BAMT-type enzymes. The
      analysis of expression patterns coupled with biochemical characterization showed
      that these carboxyl methyltransferases are involved either in floral scent
      biosynthesis or in plant defense responses. While the latter can be induced by
      biotic or abiotic stress, the genes responsible for floral scent synthesis
      exhibit developmental and rhythmic expression pattern. The nature of the product
      and efficiency of its formation in planta depend on the availability of
      substrates, the catalytic efficiency of the enzyme toward benzoic acid and/or
      salicylic acid, and the transcriptional, translational, and post-translational
      regulation at the enzyme level. The biochemical properties of benzenoid carboxyl
      methyltransferases suggest that the genes involved in plant defenses might
      represent the ancestor for the presently existing floral genes which during
      evolution gained different expression profiles and encoded enzymes with the
      ability to accept structurally similar substrates.

PMID- 15946713
TI  - Bovine herpesvirus 4-associated postpartum metritis in a Spanish dairy herd.
AB  - In more than 10 Spanish dairy cows, a bovine herpesvirus 4 (BHV4) associated
      postpartum metritis was confirmed by virus isolation, BHV4-glycoprotein B (gB)
      PCR and/or serology. In this study, 12 cows with, and, at the time of sampling, 3
      cows without clinical signs of acute postpartum metritis from one large dairy
      herd in Spain were examined for bacterial and viral infections. Blood,
      placenta/caruncles and uterine contents were collected between day 1 and day 20
      post-calving, and examined for the presence of bacteria and for viruses by virus
      isolation, BHV4 DNA by BHV4-gB PCR and/or BHV4 antibody titres. Bovine
      herpesvirus 4 was detected in 83% of the cases with clinical signs of acute
      postpartum metritis by virus isolation and/or BHV4-gB PCR. An increase of BHV4
      antibodies was detected in all examined postpartum metritis cows and in the 3
      cows without clinical metritis. Two of these 3 cows developed severe metritis a
      few dayss after collecting the first blood sample. A concurrent infections of
      BHV4 and bacteria, mainly Arcanobacterium pyogenes and Streptococcus sp., were
      detected in 73% of the examined uterine contents collected from postpartum
      metritis affected cows. This case-report study showed a clear association between
      BHV4 infections and acute postpartum metritis in dairy cows. In addition, the
      BHV4-associated postpartum metritis appeared to be an emerging syndrome in this
      Spanish herd.

PMID- 15946714
TI  - The caprine oxyhemoglobin dissociation curve.
AB  - The caprine oxyhemoglobin dissociation curve has not been previously defined.
      Blood from 10 healthy goats was equilibrated in a tonometer with calibrated gas
      mixtures of oxygen at concentrations of 95%, 21%, 13%, 12%, 10%, 9%, 8%, 5%, 4%,
      and 2.5% , 5% carbon dioxide, balance nitrogen. The pH, partial pressure of
      oxygen (PO2), partial pressure of carbon dioxide (PCO2), total hemoglobin,
      oxyhemoglobin saturation, carboxyhemoglobin, methemoglobin, and oxygen content
      were measured. The PO2/oxyhemoglobin and the PO2/oxygen content relationships
      were graphed with curve-fitting software and a formula for calculating
      oxyhemoglobin from PO2 was generated. The maximum oxygen content per gram of
      hemoglobin was 1.29 ml of oxygen per gram of hemoglobin. The PO2 at which
      hemoglobin was 50% saturated (P50) from the PO2/oxyhemoglobin relationship was
      28.6+/-1.5 mmHg and that from the PO2/oxygen content relationships was 29.1+/-1.6
      mmHg. The Hill coefficient for the PO2/oxyhemoglobin data was 3.0+/-0.4.

PMID- 15946715
TI  - Doppler ultrasonographic changes in the canine kidney during normovolaemic
      anaemia.
AB  - The haemodynamics of the canine left renal artery (LRA) and interlobar artery
      (ILA) were evaluated in eleven fasted, healthy, conscious beagles with severe
      acute (haematocrit [Hct] 16%), moderate chronic (Hct 26%) and mild chronic (Hct
      34%) normovolaemic anaemia using Doppler ultrasound. Heart rate, peak systolic
      velocity (PSV), end diastolic velocity (EDV), time-averaged mean velocity
      (TAVmean), pulsatility index (PI) and resistive index (RI) were recorded. Doppler
      values in the dogs following the induction of anaemia states were compared with
      corresponding values in the same dogs prior to the induction of anaemia. Left
      renal artery mean PSV, mean PI and mean RI were significantly higher and the mean
      EDV was significantly lower in severe acute anaemia. No significant change was
      seen in mean values of the same parameters in moderate or mild chronic anaemia.
      There was no significant change in TAVmean of the LRA or mean PI and mean RI of
      the ILA in any grade of anaemia. Acute, severe normovolaemic anaemia
      significantly altered LRA Doppler parameters in resting dogs without influencing
      those of the ILA. Moderate or mild chronic anaemia had no effect on any renal
      Doppler parameter.

PMID- 15946716
TI  - Effect of octreotide on plasma concentrations of glucose, insulin, glucagon,
      growth hormone, and cortisol in healthy dogs and dogs with insulinoma.
AB  - The inhibitory effect of the somatostatin analogue octreotide on the secretion of
      insulin could be used in the treatment of insulinoma. However, current
      information on the effectiveness of octreotide in dogs is conflicting. Therefore,
      the endocrine effects of a single subcutaneous dose of 50 microg octreotide were
      studied in healthy dogs in the fasting state (n=7) and in dogs with insulinoma
      (n=12). Octreotide did not cause any adverse effects. In healthy dogs in the
      fasting state, both plasma insulin and glucagon concentrations declined
      significantly. Basal (non-pulse related) GH and ACTH concentrations were not
      affected. A slight but significant decrease in the plasma glucose concentrations
      occurred. Dogs with insulinoma had significantly higher baseline insulin
      concentrations and lower baseline glucose concentrations than healthy dogs in the
      fasting state. Plasma glucagon, GH, ACTH, and cortisol concentrations did not
      differ from those in healthy dogs. Baseline plasma insulin concentrations
      decreased significantly in dogs with insulinoma after octreotide administration,
      whereas plasma concentrations of glucagon, GH, ACTH, and cortisol did not change.
      In contrast to the effects in the healthy dogs, in the dogs with insulinoma
      plasma glucose concentrations increased. Thus, the consistent suppression of
      plasma insulin concentrations in dogs with insulinoma, in the absence of an
      suppressive effect on counter-regulatory hormones, suggests that further studies
      on the effectiveness of slow-release preparations in the long-term medical
      treatment of dogs with insulinoma are warranted.

PMID- 15946717
TI  - Effects of zinc oxide and Enterococcus faecium SF68 dietary supplementation on
      the performance, intestinal microbiota and immune status of weaned piglets.
AB  - The objective of this study was to determine the effects of zinc oxide (ZnO) and
      the probiotic Enterococcus faecium SF68 (Cylactin) dietary supplementation on the
      performance, intestinal microbiota and immune parameters of the weaned piglet
      reared under commercial conditions. The diets were devoid of antibiotic growth
      promoters (AGP). Two hundred and eight crossbred piglets were allocated to a 2 x
      2 factorial experiment involving two levels of zinc oxide supplementation (0 or
      3100 mg ZnO/kg feed), and two levels of E. faecium SF68 supplementation (0 or 1.4
      x 10(9)CFU/kg feed (Cylactin ME10)). The diets were offered ad libitum for 20
      days post-weaning. Piglet performance was assessed by calculating average daily
      gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) on a
      pen basis. In addition, components of the distal ileal digesta, tissue-associated
      and mesenteric lymph node (MLN) bacterial populations were enumerated and serum
      immunoglobulin G (IgG) and intestinal immunoglobulin A (IgA) concentrations were
      determined on days 6 and 20 post-weaning. Regression analysis was used to
      determine the relationship between the bacterial populations at the different
      sites. Supplementation of the post-weaning diet with either ZnO or E. faecium
      SF68 did not affect piglet performance. E. faecium SF68 did not affect
      gastrointestinal bacterial populations but did tend to reduce serum IgG (P<0.1)
      on day 20. Zinc oxide reduced anaerobic (P<0.05) and tended to decrease lactic
      acid (P<0.1) bacterial translocation to the MLN, and tended to increase
      intestinal IgA concentration (P<0.1) on day 20. Generally, luminal bacterial
      populations were found to be poor predictors of tissue-associated or MLN
      populations. ZnO and E. faecium SF68 dietary supplementation were ineffective
      under these trial conditions. Further investigations into the possible
      immunomodulator role of dietary ZnO are warranted.

PMID- 15946718
TI  - New unusual pregnane glycosides with antiproliferative activity from Solenostemma
      argel.
AB  - Seven new 15-keto pregnane glycosides, namely Stemmosides E--K, were isolated
      from Solenostemma argel. Stemmosides E--J are characterized by the occurrence of
      an uncommon 14 beta proton configuration while stemmosides E and F possess in
      addition a rare enolic function in C-16. On the other hand, stemmosides G-J
      display an unusual C-17 alpha side chain. Their structures were established by
      ESI-MS and NMR experiments. Moreover, the effect of these compounds on the VEGF
      induced in Kaposi's sarcoma cell proliferation was tested. Results indicated that
      all the compounds reduced the cell proliferation in a dose dependent manner.

PMID- 15946719
TI  - Mortality and antibody responses of mice to three successive episodes of
      experimental scorpion (Centruroides limpidus limpidus) envenomation and
      immunological rescue.
AB  - Mortality rates of mice and their levels of anti-venom and anti-F(ab')2
      antibodies were assessed after three episodes of subcutaneous envenomations with
      or without treatment with horse F(ab')2. Soluble venom from the Mexican scorpion
      Centruroides limpidus limpidus was used for these experiments. Repetition of
      episodes did not induce different mortality rates in untreated mice. F(ab')2
      rescued about 85% of the mice in the first two episodes and 66% in the third,
      without distinction of gender or ostensible side-effects: a suggestion of
      selection of the most resistant mice. Surviving mice produced in vitro
      neutralizing antibodies to the scorpion venom and also antibodies to F(ab')2,
      when injected alone but more so if combined: a possible immunological adjuvant or
      alarm effect of the venom or of the cascading physiopathology of envenomation. In
      the few surviving mice, both anti-venom and anti-F(ab')2 antibodies increased
      significantly after the first envenomation but not thereafter, showing no
      correlation with mortality rates: a suggestion of their clinical irrelevance, the
      few hard-to kill mice appeared to resist envenomation by mechanisms other than
      antibody response. Injection of F(ab')2 alone induced production of detectable
      anti-venom antibodies in a few mice and injection of venom alone induced that of
      anti-F(ab')2 antibodies, perhaps due to trace amounts of venom in the high
      affinity fraction of F(ab')2 and to anti-idiotypic antibodies or polyclonal
      activity in the envenomation episode, respectively.

PMID- 15946720
TI  - Identification of cytotoxic principles from Fusarium avenaceum using bioassay
      guided fractionation.
AB  - The cytotoxicity of extracts from rice cultures of five Fusarium avenaceum
      strains against the porcine epithelial kidney cell-line PK-15 was investigated
      using the Alamar Blue assay. After the identification of known fungal
      metabolites, cytotoxic extracts were fractionated using semi-preparative reversed
      phase HPLC and normal phase LC, and the fractions were tested for cytotoxicity.
      In this way, two different groups of metabolites were identified as the major
      cytotoxic principles of the extracts. High concentrations of enniatins,
      especially enniatins B and B1, inhibited the metabolic activity of PK-15 cells.
      Furthermore, an unidentified metabolite, produced in high amounts by a strain
      that produced relatively small amounts of enniatins, was also found to be
      cytotoxic to PK-15 cells. This study shows that enniatins, a group of cyclic
      depsipeptides, which have been ignored as significant contributors to the
      toxicity of fungal extracts, may account for most of the observed effect for F.
      avenaceum.

PMID- 15946721
TI  - Three-dimensional quantitative structure activity relationship (3D-QSAR) analysis
      for in vitro toxicity of chlorophenols to HepG2 cells.
AB  - In the present paper, comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) were applied to
      investigate two 3D-QSAR models for the cytotoxicity of chlorophenols. These
      models have evaluated the intensity of chlorophenols' toxicity on HepG2 cells in
      vitro. The CoMFA model has both high consistency and predictability. The
      contribution of the electrostatic field to biological activity is greater than
      that of the steric field. The CoMSIA model used in this study includes two
      fields, one is hydrophobic field, and the other is electrostatic field. The
      relative contribution of them is 0.789:0.211. Consisted with the CoMFA model, the
      CoMSIA electrostatic filed also plays a dominant role. The CoMFA and CoMSIA
      contour maps significantly elucidated that the electrostatic field is more
      important than the other fields and might be one of the reasons resulting in
      potential reactive mechanism involved in cell proliferation inhibition.

PMID- 15946722
TI  - Linear free energy relationships on rate constants for the gas-phase reactions of
      hydroxyl radicals with PAHs and PCDD/Fs.
AB  - Polyparameter linear free energy relationships (LFERs) on rate constants (kOH)
      for gas-phase reactions of hydroxyl radicals with polycyclic aromatic
      hydrocarbons (PAHs) and polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) were developed. Quantum chemical descriptors and partial least squares
      (PLS) regression were used for model development. Acenaphthylene was found to be
      an outlier and was excluded in the final model development. The cumulative
      variance of the dependent variable explained by the PLS components and determined
      by cross-validation (Q2(cum)), for the optimal model, is 0.97, indicating good
      robustness and predictive power of the model. The main molecular structural
      factor governing kOH values of PAHs and PCDD/Fs is molecular ability to donate
      electrons, as described by the energy of the highest occupied molecular orbital
      (E(HOMO)), the average of net atomic charges on hydrogen atoms (qH(+)), and the
      average of net atomic charges on carbon atoms (qC). PAH and PCDD/F molecules with
      high E(HOMO) and low qH(+) and qC values tend to have high log kOH values. The
      LFER model indicates the temperature dependence of log kOH is weak.

PMID- 15946723
TI  - Systematic analysis and overall toxicity evaluation of dioxins and
      hexachlorobenzene in human milk.
AB  - A systematic method for analyzing dioxins (PCDDs, PCDFs and dioxin-like PCBs),
      hexachlorobenzene (HCB), heptachlor epoxide and beta-hexachlorocyclohexane (HCH)
      in human milk was developed to determine the residual amount of HCB in human milk
      and to evaluate the overall toxicity of both dioxins and HCB in human milk. The
      fractionation behavior of HCB on chromatography with silica gel, alumina, and
      activated carbon/silica gel, and the concentrated sulfuric acid decomposition
      method, which is widely used as a dioxin cleanup method, were studied in order to
      make the preprocessing operation for HCB measurement compatible with that for
      conventional dioxin measurement. HCB was found to be eluted in the 2%
      dichloromethane (DCM)/hexane 60 ml fraction from an alumina column. Heptachlor
      epoxide and a part of beta-HCH were eluted in the 10% DCM/hexane 50 ml fraction
      from a silica gel column, while the remaining beta-HCH was eluted in the 25%
      DCM/hexane 60 ml fraction from an activated carbon/silica gel column. Moreover,
      HCB showed significant correlation with dioxin congeners having high toxicity
      equivalence factors (TEFs). The results suggest that the exposure route to HCB
      and its accumulation behavior in the human body are similar to those of the
      dioxins.

PMID- 15946724
TI  - Inhibition of PCDD/Fs formation from dioxin precursors by calcium oxide.
AB  - Research aimed at understanding the inhibition effect of CaO on polychlorinated
      dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) formation form dioxins precursors,
      such as chlorophenols (CPs) and chlorobenzenes (CBs). The results indicated that
      a clear dioxin inhibition effect occurred both in open and sealed system when CaO
      was used. In the open system, PCDDs were the main congeners and the inhibition
      efficiency was all over 99% in the experiments. In the experiments with CaO, less
      than 0.1% of the initial PCP was detected in the absorption tube and only about
      1% of the initial PCP was examined as calcium pentachlorophenate in the reaction
      tube. In the sealed system, the inhibition efficiency was over 90% at temperature
      range between 280 and 450 degrees C when PCP was used as model precursor. When
      HCB and 2,3,4,5-T4CP replaced PCP, significant inhibition effect was also
      observed. As CaO has the advantageous properties of non-toxicity and non-volatile
      nature, it is our hope that the result will contribute to the development of a
      new technique to cope with the problem of dioxin pollution in MWIs.

PMID- 15946725
TI  - Isotope dilution analysis of polychlorinated biphenyls (PCBs) in transformer oil
      and global commercial PCB formulations by high resolution gas chromatography-high
      resolution mass spectrometry.
AB  - Special polychlorinated biphenyls (PCBs) standards (native and isotope labeled)
      were analyzed by isotope dilution method using HRGC-HRMS. Multiple analysis of
      special PCBs standards by three different laboratories produced the relative
      response factors (RRFs) and relative standard deviations (RSDs %) was in the
      average of 0.979 and 3.86, respectively. Additionally, inter-laboratory analysis
      of various forms of transformer oil revealed the PCBs concentrations were in the
      following order; PCBs fortified transformer oil (940-1300 ng/g)>PCB polluted
      transformer oil (490-680 ng/g)>chemically degraded-transformer oil (480-490 ng/g)
      and PCBs free oil (ND-17 ng/g). Chemical degradation resulted in an order of
      magnitude decrease in the PCB concentrations. Specifically, higher chlorinated
      PCBs degraded into lower chlorinated PCBs. Also, composition of PCBs have been
      determined in PCB formulations from Japan (Kanechlor), Germany (Clophen), USA
      (Aroclor), Russia (Sovol) and Poland (Chlorofen). Major PCBs (24-PCB congeners)
      contributed 54-67%, 55-68%, 16-69%, 71% and 72% in Kanechlor, Clophen, Aroclor,
      Sovol and Chlorofen, respectively to total PCBs. The homologue pattern of
      Kanechlor, Aroclor and Clophen in technical fromulation was similar (e.g.,
      Kanechlor-300 resembled to those of Clophen A-30 and Aroclor-1242). Furthermore,
      congener-specific distributions of major PCBs/dioxin-like PCBs and toxic
      equivalency quantities (TEQ) were calculated. Based on our tentative assumption
      calculations, cumulative production of five different technical PCB formulations,
      WHO-TEQ emission was estimated to be approximately 16.05 tons.

PMID- 15946726
TI  - Cadmium accumulation and Cd-binding proteins in marine invertebrates--a
      radiotracer study.
AB  - Tissue and subcellular accumulation of cadmium were studied in different tissues
      of three marine invertebrates (blue mussel Mytilus edulis, the tunicate Ciona
      intestinalis and the sea star Asterias rubens) using radioactive 109Cd as a
      tracer. The organisms were exposed to 0.05, 2 and 50 microg Cd l(-1) for 21 days.
      Quantitative data were obtained by dissecting, weighing and subsequently
      measuring radioactivity in organs and tissues. Differences between each exposure
      and each tissue with regard to the amount of radioactivity and metallothionein
      (MT) content were evaluated. Obvious interspecies differences in Cd accumulation
      were observed, as well as differences between tissues of the three species. The
      highest concentrations of Cd in all exposure treatments were found in the
      hepatopancreas of M. edulis and body wall of A. rubens. Taking all treatments
      into account, Cd accumulation in the tunic of C. intestinalis was high compared
      to other tissues from this species. Over 60% of Cd was present in the S50
      fraction in all treatments in all three species. Metallothionein levels were
      increased at the highest Cd-exposure in all species and tissues, except in
      branchial pharynx of C. intestinalis where the highest MT level was reached
      following exposure to 2 microg Cd l(-1). The most surprising finding was that
      even the lowest Cd exposure concentration (0.05 microg Cd l(-1)) caused MT
      induction in pyloric caeca of A. rubens, but there was no dose-dependent increase
      in MT at higher exposure levels.

PMID- 15946727
TI  - Determination of polybrominated diphenyl ethers in soil and sediment from an
      electronic waste recycling facility.
AB  - Soil and sediment collected in the vicinity of an open electronic waste disposal
      and recycling facility located in Guiyu, Guangdong, China, were analyzed for the
      levels of common polybrominated diphenyl ethers (PBDEs) by using soxhlet
      extraction and gas chromatography/mass spectrometry. The PBDEs were detected in
      the soil and sediment samples at levels of 0.26-824 ng/g (dry weight). The
      obtained isomer profiles of PBDEs from the two soil samples collected from
      different contamination sites were found to be similar to various technical
      formulations of fire retardant products.

PMID- 15946728
TI  - Cognitive aging as an extension of brain development: a model linking learning,
      brain plasticity, and neurodegeneration.
AB  - Differences in cognitive aging rates among mammals suggest that the pace of brain
      aging is genetically determined. In this work, we investigate the possibility
      that brain aging is an extension of brain development. It is possible that a
      subset of developmental mechanisms are extreme cases of antagonistic pleiotropy
      in that they are necessary for reaching adulthood and yet later cause age-related
      diseases. We derive a model linking development and brain aging in which
      childhood events essential for brain development later result in
      neurodegeneration. The hypothesis presented herein involves brain plasticity in
      which the same mechanisms that shape the adult phenotype continue at later ages
      contributing to cognitive dysfunction and eventually dementia. The same genetic
      program that decreases brain plasticity at early ages to focus our mind to the
      surrounding environment may continue in adulthood resulting in cognitive aging.
      Experimental implications for understanding neurodegeneration in this context are
      also discussed.

PMID- 15946729
TI  - Profiles of short chain oligomers in roach (Rutilus rutilus) exposed to
      waterborne polyethoxylated nonylphenols.
AB  - Nonylphenol polyethoxylates (NPEOs) are common contaminants in the aquatic
      environment through their use as industrial surfactants and their discharge in
      wastewaters and effluents. In order to assess the bioavailability of NPEOs to
      fish, we studied the fate of two different oligomeric mixtures of NPEOs in adult
      roach Rutilus rutilus. Fish were exposed to [14C] radiolabelled NPEOs, averaging
      either 3 ethoxy units (NP(3av)EO) or 7 ethoxy units (NP(7av)EO), over a 4-day
      period in a flow-through aquarium. A method was developed to extract radioactive
      residues from soft tissues and analyse their composition by normal phase radio
      HPLC and GC-MS. Radioactive residues were detected in all soft tissues of the
      roach dosed with either of the test mixtures, but the concentration of NPEO
      residues in each tissue were highest in fish exposed to the NP(3av)EO compared
      with the NP(7av)EO test mixture. Radioactive concentrations in roach dosed with
      14C NP(3av)EO were highest in the bile at a mean concentration+/-S.E. of 62+/-3
      microg/g wet weight, whereas concentrations in the liver, kidney and brain
      tissues ranged between 1 and 2 microg/g and concentrations in other soft tissues
      were between 0.1 and 0.7 microg/g. Analysis of the radioactive residues in bile
      of roach exposed to the NPEO test mixtures indicated that they were mainly
      metabolites including glucuronide conjugates, whereas in muscle, ovary and gill
      tissues they were a mixture of NP and short chain NPEO oligomers comprising 1-4
      ethoxy units. This study suggests that short chain NPEO oligomers are taken up
      via the gills and accumulate in tissues such as gonads which are sensitive to
      endocrine disruption, whereas waterborne NPEOs containing more than 4 ethoxymers
      are not bioavailable to roach.

PMID- 15946730
TI  - Pregnancy after radical vaginal trachelectomy: maybe not such a risky undertaking
      after all.

PMID- 15946731
TI  - Cross-tolerance and mu agonist efficacy in pigeons treated with LAAM or
      buprenorphine.
AB  - The mechanism responsible for decreased opioid use during opioid substitution
      therapy is not fully understood. To examine whether l-alpha-acetylmethadol (LAAM)
      or buprenorphine attenuate behavioral effects of opioids through cross-tolerance,
      discriminative stimulus effects of high and low efficacy mu agonists were
      examined following 3- or 7-day treatment with LAAM or buprenorphine in pigeons
      discriminating between saline and heroin or between saline and buprenorphine,
      respectively. Heroin, buprenorphine and nalbuphine occasioned high levels of drug
      appropriate responding in both groups; kappa opioids and non-opioids occasioned
      predominantly saline-appropriate responding. Administration of LAAM (3.2 mg/kg)
      or buprenorphine (3.2 mg/kg) occasioned predominantly heroin- or buprenorphine
      appropriate responding, respectively. After discontinuation of LAAM treatment,
      the potency in occasioning heroin-key responding was markedly decreased for
      nalbuphine, slightly decreased for buprenorphine, and unchanged for heroin.
      Following discontinuation of buprenorphine treatment, the potency in occasioning
      buprenorphine-key responding was decreased for nalbuphine and unchanged for
      buprenorphine and heroin. Thus, greater cross-tolerance developed from LAAM and
      buprenorphine to low efficacy mu agonists as compared to a higher efficacy
      agonist. Failure of LAAM and buprenorphine treatment to modify the effects of
      heroin, under conditions that attenuate the effects of lower efficacy mu opioids,
      provides a possible rationale for why heroin abuse persists in some patients
      receiving large doses of agonists in substitution therapy.

PMID- 15946732
TI  - Reproductive behavior of small animals.
AB  - Normal and abnormal reproductive behavior of dogs and cats, and known and
      proposed hormonal bases for these behaviors are addressed. Emerging information
      includes use of oxytocin to promote pair-bonding between dam and offspring and
      the possible effect of prolactin in inhibiting sexual behaviors.

PMID- 15946733
TI  - New techniques for the assessment of canine semen quality: a review.
AB  - Until recently, canine semen assessment was routinely performed by conventional
      light microscopic techniques. The limitations of these methods include
      subjectivity, variability, the small number of spermatozoa analyzed, and poor
      correlation with fertilizing potential. The last decade, several new in vitro
      techniques have been introduced for canine semen assessment that enable a more
      detailed evaluation of several sperm characteristics. Numerous fluorescent
      staining techniques have been developed for the evaluation of specific sperm
      characteristics and functions, including plasma membrane integrity, capacitation
      status and the acrosome reaction. By combining fluorescent stains, several
      functional sperm characteristics can be assessed simultaneously. Moreover, by
      means of flow cytometry, large numbers of fluorescently labelled spermatozoa can
      be analysed in a short interval. Following thorough standardization and
      validation, computer-assisted sperm analysis systems provide objective and
      detailed information on various motility characteristics and morphometric
      dimensions that cannot be identified by conventional light microscopic semen
      analysis. In vitro assays, evaluating the capacity of canine spermatozoa to bind
      to the zona pellucida or oviductal explants, or to penetrate the oocyte, provide
      additional information on canine gamete interaction that may be useful in
      predicting the fertilizing potential of spermatozoa. Although substantial
      improvements have been made in canine semen assessment, surprisingly few
      parameters were correlated with in vivo fertility. Therefore, further research is
      required to determine which sperm characteristics are of clinical value for
      predicting the in vivo fertility in dogs.

PMID- 15946734
TI  - Fertility evaluation of frozen/thawed semen.
AB  - In vitro semen analyses have been used for more than half a century to estimate
      the fertilizing potential of a semen sample. Unfortunately, none of the assays
      developed provide results that consistently correlate well with fertility. The
      reasons for this lack of consistency, due in part to the complexity of the
      spermatozoon itself, the collection of fertility data, and factors beyond control
      of the semen analyses themselves, are discussed. Different spermatozoal
      attributes that are necessary for a spermatozoon to fertilize an oocyte are
      presented and assays used to evaluate each attribute described. Although
      laboratory assay results do not correlate well with semen fertility, the
      importance of conducting laboratory assays on every semen sample used for
      artificial insemination or to attempt to determine causes for infertility, is
      discussed.

PMID- 15946735
TI  - Reproductive biology in the era of genomics biology.
AB  - Current and emerging technologies in reproductive biology, including assisted
      reproductive technologies and animal cloning, are discussed in the context of the
      impact of genomics era biology. The discussion focuses on the endocrinology
      associated with establishment and maintenance of pregnancy, fetal-placental
      development, lactation, and neonatal survival. Various aspects of uterine
      biology, including development during the neonatal period and function in adult
      females, are discussed with respect to reproductive efficiency. It is clear that
      combining strategies for use of conventional animal models for studying the
      reproductive system with new genomics technologies will provide exceptional
      opportunities in discovery research involving data integration and application of
      functional genomics to benefit animal agriculture and the biomedical community.
      New and emerging biotechnologies and comparative genomics approaches will greatly
      advance our understanding of genes that are critical to development of the
      reproductive system and to key events at each stage of the reproductive cycle of
      females and males.

PMID- 15946736
TI  - Construction of anti-adhesive and antibacterial multilayer films via layer-by
      layer assembly of heparin and chitosan.
AB  - Chitosan as an antibacterial agent and heparin as an anti-adhesive agent were
      alternatively deposited onto aminolyzed poly(ethylene terephthalate) (PET) films
      to construct anti-adhesive and antibacterial multilayer films. The contact-angle
      and UV data verified the progressive buildup of the multilayer film by alternate
      deposition of the polyelectrolytes. The properties of multilayer films were
      investigated by contact angle, atomic force microscopy (AFM), lateral force
      microscopy (LFM) and UV spectra. The results of initial adhesion of Escherichia
      coli (E. coli) on PET substrates showed that the number of E. coli adhered onto
      the control PET was in a much greater extent than onto the chitosan/heparin
      multilayer films, and the number of adhesive bacteria decreased with a decrease
      in assembly pH. The in vitro antibacterial test indicated that a multilayer of
      chitosan/heparin could kill the bacteria effectively. The number of viable
      bacteria decreased by 7% after 7 h in contact with the control PET films, but by
      46-68% for the multilayer-modified PET films. Only 3-8% of the cells were viable
      for the multilayer-modified PET films after 24h. It is interesting to find the
      assembly pH has a remarkable effect on the antibacterial property of the
      multilayer. The number of viable bacteria on the multilayer assembled at pH =
      3.8, 2.9 and 6.0 decreased by 68%, 58% and 46%, respectively. Such an easy
      processing and shape-independent method to prepare an anti-adhesive and
      antibacterial surface may have good potential for surface modification of
      cardiovascular devices.

PMID- 15946737
TI  - Effects of lyophilization on the infectivity of enveloped and non-enveloped
      viruses in bone tissue.
AB  - Recently reported qualitative experiments proved that retroviral infectivity is
      not destroyed by lyophilization performed on systemically infected bone and
      tendon. The now accomplished quantitative determination of residual infectivity
      for enveloped and non-enveloped viruses allows a validation of the production
      process regarding viral safety in freeze-dried bone transplants. The
      lyophilization effect on the infectivity of two non-enveloped viruses (Maus
      Elberfeld virus, MEV; Porcine parvovirus, PPV) and one enveloped virus (Vesicular
      Stomatitis virus, VSV) was examined for virus-spiked bone material in comparison
      to lyophilized viruses, original virus stock, and air-dried viruses. All
      experiments were carried out with both cell-free and cell-associated virus.
      Significant differences were observed regarding the reduction of virus titers
      (TCID50). Infectivity of VSV was reduced by about 3-4 log10 using lyophilization
      in presence of bone matrix and of MEV by 6-7 log10, while no substantial
      reduction in virus titers was observed for PPV. Lyophilization of cell-free or
      cell-associated virus is not sufficient to inactivate viruses completely.
      However, lyophilization could have an additive effect in line with other
      production steps used in the manufacturing process.

PMID- 15946738
TI  - The application of polyhydroxyalkanoates as tissue engineering materials.
AB  - Polyhydoxyalkanoates (PHA) are polyesters produced by microorganisms under
      unbalanced growth conditions. They are generally biodegradable and
      thermoprocessable, making them attractive as biomaterials for applications in
      both conventional medical devices and tissue engineering. Over the past years,
      PHA, particularly poly 3-hydroxybutyrate (PHB), copolymers of 3-hydroxybutyrate
      and 3-hydroxyvalerate (PHBV), poly 4-hydroxybutyrate (P4HB), copolymers of 3
      hydroxybutyrate and 3-hydroxyhexanoate (PHBHHx) and poly 3-hydroxyoctanoate (PHO)
      and its composites have been used to develop devices including sutures, repair
      devices, repair patches, slings, cardiovascular patches, orthopedic pins,
      adhesion barriers, stents, guided tissue repair/regeneration devices, articular
      cartilage repair devices, nerve guides, tendon repair devices, bone marrow
      scaffolds, and wound dressings. The changing PHA compositions also allow
      favorable mechanical properties, biocompatibility, and degradation times within
      desirable time frames under specific physiological conditions. This paper reviews
      what have been achieved in the PHA tissue engineering area and concluded that the
      PHA prospective will look very bright in the near future.

PMID- 15946739
TI  - The conflicting roles of the cdk inhibitor p21(CIP1/WAF1) in apoptosis.

PMID- 15946740
TI  - Combined effect of biopesticides on the digestive enzymatic profiles of
      Cnaphalocrocis medinalis (Guenee) (the rice leaffolder) (Insecta: Lepidoptera:
      Pyralidae).
AB  - Plant extracts, especially botanical insecticides, are currently studied more and
      more because of the possibility of their use in plant protection. Many of the
      natural plant compounds and organic compounds used in the control of insect pests
      are known to affect digestive enzymes. When fed a diet of rice leaves treated
      with botanical insecticides and bacterial toxins in bioassays, activities of the
      digestive enzymes protease, amylase, and lipase in the rice leaffolder larvae are
      affected. Digestive enzyme activities were affected by botanical insecticides and
      bacterial toxins individually and in combination. When combined, the effect was
      more severe at low concentration. There were statistically significant
      differences (P < or = 0.05) in enzyme activities in combined and individual
      treatments. The combination of Btk and botanical insecticides caused a two-fold
      decrease in enzyme activity even at reduced concentration. Clear dose-response
      relationships were established with respect to enzyme activity. A synergistic
      effect of botanical insecticides and bacterial toxins was found when combined in
      low doses. These effects are most pronounced in early instars.

PMID- 15946741
TI  - Protecting elders: regulating intergenerationally transmitted debt in Australia.
AB  - Australia, like other western nations, is facing the prospect that in the decades
      ahead the overall population will age dramatically. This article considers legal
      issues associated with the aged and intergenerationally transmitted debt. It will
      be argued that the present legal regulation of guarantees is a complex amalgam of
      case law, statute and finance industry self-regulatory codes which does not
      necessarily or adequately take into account the particular vulnerabilities of the
      aged and the very old or the intergenerational pressures which they may confront.
      It may be necessary to take significant steps to protect vulnerable elders while
      still recognizing their rights to exercise personal autonomy. Some proposals for
      reform are made.

PMID- 15946742
TI  - Acute and sub-lethal toxicity of landfill leachate towards two aquatic macro
      invertebrates: demonstrating the remediation potential of air stripping.
AB  - A specific leachate that contained 1.036 mg l(-1) of 2-chlorobiphenyl was used in
      the study (255 mg l(-1) COD and 133 mg l(-1) BOD5). Bench scale (20 l) air
      stripping trials were used to simulate on a small-scale the treatment potential
      of this method. Air stripping effectively reduced the leachates COD
      concentration. Regardless of the volume of air supplied (1-5 l of air per minute)
      the leachates COD reached a <50 mg l(-1) equilibrium after 96-h exposure,
      however, increasing the volume of air accelerated the process. In untreated
      leachate, the LC50 for Asellus aquaticus was 57% v/v leachate in deionised water
      and 5% for Gammarus pulex (96-h, static LC50 tests without nutrition and oxygen
      depleting conditions). After being exposed to air stripping, these values rose
      from 90% to below the LC50 threshold for Asellus when 1-5 l of air per minute
      were applied and 30-90% for Gammarus. Furthermore, in sub-lethal concentrations
      of air stripped leachate (leachate that had been exposed to 5-l of air per minute
      for 96-h) the population dynamics of both test species remained unaltered.

PMID- 15946743
TI  - Gamma interferon-producing CD4 T-cells correlate with resistance to Mycoplasma
      mycoides subsp. mycoides S.C. infection in cattle.
AB  - Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp.
      mycoides SC (MmmSC), is one of the most significant cattle disease in Africa. The
      control measures, which led to eradication from numerous countries are not
      feasible in Africa where the only prophylaxis relies on vaccination. However, the
      attenuated vaccines, used up to now in Africa, are of low efficiency. The
      development of an improved vaccine is, therefore, a necessity. The purpose of
      this study was to compare some immunological parameters in MmmSC-infected cattle
      (endobronchial versus natural in-contact infection) and assess the response in
      correlation with the clinical outcome (death versus recovery). Characterization
      of the immune parameters elicited in recovered animals, known to be refractory to
      new infection, will be an important step towards development of new vaccines
      against CBPP. A significant outcome of this study was the demonstration that all
      MmmSC-infected cattle developed a MmmSC-specific cell-mediated immune response. A
      kinetic analysis of the MmmSC responsiveness showed that the main difference
      between endobronchially- and in-contact infected animals was the delay before the
      onset of the MmmSC-specific immune response. The first MmmSC-responding PBMC
      sample was selected from each animal for cell phenotyping. The phenotypic
      analysis of this early MmmSC-induced response revealed the predominant
      contribution of the CD4 T-cells in all animals whereas IFNgamma was only
      constantly produced in recovered animals. Evolution of this early MmmSC-specific
      immune response was then followed by a kinetic analysis of the MmmSC-induced CD4
      T-cell response and IFNgamma released. The results demonstrated that in recovered
      animals, the MmmSC-specific CD4 Th1-like T-cell response was maintained until
      slaughtering whereas in animals with acute disease, progression of CBPP was
      associated with a decreased ability of the PBMC to produce IFNgamma. The results
      led to the identification of immune parameters, which correlate with protection
      against CBPP and to a relevant strategy for the development of improved vaccines
      against this disease.

PMID- 15946744
TI  - Frequent respiratory tract infections in the canine model of X-linked ectodermal
      dysplasia are not caused by an immune deficiency.
AB  - As in many human patients with X-linked hypohidrotic ectodermal dysplasia (XHED),
      XHED dogs are at an increased risk for pulmonary disorders. Localized immune
      system defects had been suspected previously in affected dogs because of frequent
      infections and unexpected deaths due to opportunistic respiratory tract
      infections. Experiments were designed to examine systemic and localized humoral
      and cellular responses, development and function of T cells, and thymic
      morphology. All dogs used in these experiments were clinically healthy at the
      time of examination and their immune responses were compared to normal
      littermates. Serum immunoglobulin concentrations differed somewhat between normal
      dogs and dogs affected with XHED but they were all within normal ranges. The XHED
      dogs responded appropriately to vaccination with tetanus toxoid suggesting normal
      systemic B and plasma cell function. Thymic morphology was compared between
      normal and affected dogs and T cells were assessed for functionality. Numbers and
      phenotypes of T and B cells in blood and thymus of affected dogs were within
      normal limits suggesting normal development of T cells. Cytotoxic and phagocytic
      ability of macrophages and neutrophils was also normal in affected dogs. In
      contrast, the secretory IgA concentrations found in affected dogs were
      significantly higher than in normal dogs, while lacrimal secretions were
      significantly decreased. These results suggest a compensatory mechanism for
      secretory IgA, so that the total amount equals that in normal dogs. The results
      presented in this study indicate that the XHED dogs have a relatively intact
      immune system and suggest that the same is true for humans with the homologous
      form of XHED.

PMID- 15946745
TI  - Cytokine gene expression profiles of bovine dendritic cells after interaction
      with Mycobacterium avium ssp. paratuberculosis (M.a.p.), Escherichia coli (E.
      coli) or recombinant M.a.p. heat shock protein 70.
AB  - Mycobacterium avium paratuberculosis (M.a.p.) resides and replicates in
      macrophages. Many of the of immune mechanisms aiding M.a.p. survival in the
      host's cells are known. However, little is known about interactions of M.a.p.
      with dendritic cells (DC). As DC are important for the induction of protective
      immunity against infectious diseases, we investigated the interaction of M.a.p.
      with these cells. Quantitative real-time PCR (RT-PCR) was used to analyse
      differential expression of cytokine genes after 6 h and 24 h of incubation by
      immature DC that phagocytosed either M.a.p. or Escherichia coli (E. coli). We
      hypothesized that phagocytosis of E. coli would induce pro-inflammatory cytokines
      due to abundant presence of lipopolysaccharide (LPS) and that the cytokine
      expression profile induced by phagocytosis of live M.a.p. would differ. In
      addition we hypothesized that incubation of immature DC with rHsp70, an
      immunodominant antigen of M.a.p., would induce a similar profile of cytokine gene
      expression as phagocytosis of intact M.a.p. However, phagocytosis of both E. coli
      and M.a.p. resulted in a cytokine gene expression pattern representative of a
      (pro-)inflammatory reaction, dominated by strong induction of IL-12 gene
      expression, that was higher after 24 h than after 6 h of incubation, although the
      response to M.a.p. was less vigorous than to E. coli. Incubation with rHsp70
      resulted in a more inhibitory type of cytokine gene expression, with delayed IL
      12 gene expression and downregulation of the genes for IL-1beta and IL-6 after 24
      h of incubation. We conclude that bovine DC produce an immuno-stimulatory, anti
      mycobacterial response to infection with M.a.p., while Hsp70 potentially
      contributes to pathogen virulence by allowing the bacteria to invade the host
      cell.

PMID- 15946746
TI  - Health-related quality of life of Austrian children and adolescents with cochlear
      implants.
AB  - BACKGROUND AND OBJECTIVE: As shown by many studies, deaf children benefit
      considerably by cochlear implants (CI), concerning oral language and integration
      in mainstream schools. This had lead to the general view of a good quality of
      life of these children. Unfortunately so far nearly no studies on quality of
      life, and specially no studies on health-related quality of life (HRQoL) of
      children with cochlear implants, have been published. The present study with the
      objective for first, initial information on health-related quality of life of
      Austrian pupils with cochlear implants is a first step to fill this gap. METHODS:
      Forty-four Austrian pupils, out of 65 candidates, age 8-16, with a hearing
      experience of at least 3 years with implants, and their parents were surveyed in
      the CI Center, Salzburg (cross sectional study). Basic medical and audiological
      data were available for all pupils. Because of reading comprehension difficulties
      15 pupils were excluded. Parents and children were surveyed with the KINDLr, a
      generic instrument for health-related quality of life of children and
      adolescents. Main outcome measures were the HRQoL-total scores (mean, transformed
      to 100, standard deviation). In addition, 95% confidence intervals, effect sizes,
      t scores (one- and two-sided t-tests), rank order correlations and coefficients
      of determination were calculated. RESULTS: The HRQoL-total score of the children
      with CI (n=18), age 8-12 was below the standard for hearing children (P<0.001).
      It differed from the total score of the parent rating (P<0.0001). The difference
      between the parent ratings of non-excluded and of excluded children (n=12) was
      not significant. The total score of the adolescents (n=11), age 13-16 was within
      the norm, with no significant difference between adolescent and parents. The
      total scores correlate with parent-child agreement in the ratings, with outcomes
      of audiological speech tests, length of time of deafness, and age at
      implantation. CONCLUSIONS: Children with CI experience a lower health-related
      quality of life, compared to hearing children, with a low parent-child agreement.
      The findings of this study point to a normal subjective health of adolescents
      with CI.

PMID- 15946747
TI  - Principles: a model for the allosteric interactions between ligand binding sites
      within a dimeric GPCR.
AB  - Increasing evidence suggests that most, if not all, G-protein-coupled receptors
      have the propensity to dimerize. The dimerization process can lead to crosstalk
      between the protomers and can result in cooperative binding of ligands to these
      protomers. However, many results suggest that the crosstalk between protomers
      within a dimer is not permanent. Receptors oscillate between two states: one that
      enables binding sites to crosstalk and another that does not enable such
      crosstalk. In this article, the consequences of the equilibrium between these two
      states on the binding properties of a receptor are analyzed using the predictions
      of two mathematical models.

PMID- 15946748
TI  - Long-lasting cognitive improvement with nicotinic receptor agonists: mechanisms
      of pharmacokinetic-pharmacodynamic discordance.
AB  - Agonists of nicotinic acetylcholine receptors (nAChRs) produce long-lasting
      cognitive effects in animal models and humans. The duration of these cognitive
      effects can outlast the presence of the agonists in the system, and the
      persistence of cognitive enhancement is increased further by repeated exposure.
      The basis for this discrepancy appears be the cellular and systemic mechanisms of
      learning and memory. Agonists of nAChRs induce long-term potentiation (LTP),
      which is a strengthening of synaptic connections that is associated with learning
      and memory formation. Some of the cellular effects of nAChR agonists overlap with
      the known cellular mechanisms of LTP, including long-lasting increases in
      intracellular concentrations of Ca2+, activation of second-messenger systems and
      transcription factors, elevated levels of gene products and enhanced
      neurotransmitter release. A better understanding of this phenomenon might shed
      new light on the role of nAChR systems in memory formation and retrieval.

PMID- 15946749
TI  - Serogroup-reactive and type-specific detection of bluetongue virus antibodies
      using chicken scFvs in inhibition ELISAs.
AB  - Two bluetongue virus (BTV) serotype 10-specific single-chain Fv chicken antibody
      fragments (scFvs) were evaluated in a competitive ELISA. The binding of one (F3)
      to purified BTV was only inhibited by antibodies against the homologous serotype.
      The binding of the other (F10) was blocked by antisera to each of the 24 BTV
      serotypes. F10 recognised VP7, a major structural protein of the BTV core, but
      not if the protein was directly adsorbed to a plastic surface. It did, however,
      bind to recombinant VP7 that had been captured from suspension by rabbit IgG.
      This made it possible to develop an scFv based inhibition ELISA for BTV
      antibodies using recombinant VP7 without prior purification. The resulting
      immunoassay detected antibodies to 24 BTV serotypes, but not those directed
      against three serotypes of the related epizootic haemorrhagic disease virus. A
      phage library displaying fusion peptides expressed by fragments of the BTV genome
      segment 7 cDNA was constructed and screened using F10. Comparing selected
      peptides with the amino acid sequence of VP7 showed that recognition by the scFv
      required at least 131 residues representing the protein's upper domain. By
      providing well-characterised immunological reagents, recombinant antibody
      technology can contribute to the development of improved immunoassays for BTV
      diagnosis.

PMID- 15946750
TI  - Ghrelin regulates adiposity in white adipose tissue and UCP1 mRNA expression in
      brown adipose tissue in mice.
AB  - To examine the involvement of ghrelin in obesity, we investigated the effects of
      treatment with peripherally administered ghrelin on food intake, adiposity, and
      expression of uncoupling protein (UCP) mRNA in brown (BAT) and white (WAT)
      adipose tissue in mice. Acute bolus administration of ghrelin at a dose of 120
      nmol/kg increased cumulative food intake over 4 and 24 h as compared to controls
      (p<0.05 for each), whereas 12 nmol/kg/day ghrelin showed no remarkable effect
      (p>0.1). Chronic repeated treatment with 12 nmol/kg/day ghrelin for 7 days
      increased body weight and adiposity assessed by the weight of adipose tissue,
      triglyceride content in WAT (p<0.05 for each versus control). In addition, the
      same treatment decreased and increased mRNA expression of BAT UCP1 and WAT UCP2,
      respectively (p<0.05 for each). In conclusion, ghrelin can regulate body weight,
      adiposity and UCPs mRNA expression in mice. The present results provide evidence
      for a new regulatory loop involving ghrelin and UCP, and add novel insights into
      the regulatory mechanisms of obesity.

PMID- 15946751
TI  - Isolation and expression analysis of genes encoding DNA methyltransferase in
      wheat (Triticum aestivum L.).
AB  - DNA methylation of cytosine residues, catalyzed by DNA methyltransferases, is
      suggested to play important roles in regulating gene expression and plant
      development. In this study, we isolated four wheat cDNA fragments and one cDNA
      with open reading frame encoding putative DNA methyltransferase and designated
      TaMET1, TaMET2a, TaMET2b, TaCMT, TaMET3, respectively. BLASTX searches and
      phylogenetic analysis suggested that five cDNAs belonged to four classes (Dnmt1,
      Dnmt2, CMT and Dnmt3) of DNA methyltransferase genes. TaMET2a encoded a protein
      of 376 aa and contained eight of ten conserved motifs characteristic of DNA
      methyltransferase. Genomic sequence of TaMET2a was obtained and found to contain
      ten introns and eleven exons. The expression analysis of the five genes revealed
      that they were expressed in developing seed, during germination and various
      vegetative tissues, but in quite different abundance. It was interesting to note
      that TaMET1 and TaMET3 mRNAs were clearly detected in dry seeds. Moreover, the
      differential expression patterns of five genes were observed between wheat hybrid
      and its parents in leaf, stem and root of jointing stage, some were up-regulated
      while some others were down-regulated in the hybrid. We concluded that multiple
      wheat DNA methyltransferase genes were present and might play important roles in
      wheat growth and development.

PMID- 15946752
TI  - beta-catenin signaling and regulation of cyclin D1 promoter in NRK-49F cells
      transformed by down-regulation of the tumor suppressor lysyl oxidase.
AB  - Lysyl oxidase is the enzyme that is essential for collagen and elastin cross
      linking. Previous investigations showed that lysyl oxidase is down-regulated in
      many human tumors and ras-transformed cells. Recently, we proved that antisense
      down-regulation of lysyl oxidase in NRK-49F cells induced phenotypic changes and
      oncogenic transformation, characterized by p21(ras) activation and beta
      catenin/cyclin D1 up-regulation. In the present paper, we examined beta-catenin
      intracellular distribution and its association with E-cadherin. We observed an
      increased association between E-cadherin and beta-catenin in the lysyl-oxidase
      down-regulated cells during serum starvation. Moreover, we found that beta
      catenin cytoplasmic and nuclear levels were increased, suggesting a failure of
      its down-regulation by the APC-GSK-3beta system, in particular the GSK-3beta
      phosphorylation of ser-33/37 and thr-41 of beta-catenin. Finally, we investigated
      the mechanisms leading to the observed cyclin D1 up-regulation. We showed that in
      the antisense lysyl oxidase cells the cyclin D1 promoter was activated through
      the LEF and the ATF/CRE sites in the proximal promoter. While the promoter
      activation through LEF is compatible with beta-catenin signaling, we investigated
      the possibility that the CRE-dependent activation might be linked to the down
      regulation of lysyl oxidase. In fact, up-regulation of lysyl oxidase in a COS-7
      cell model showed a significant diminution of the CREB protein binding to the
      cyclin D1 promoter, leading to a dramatic inhibition of its activity and a
      significant down-regulation of cyclin D1 protein level in vivo. Finally, our
      study describes some major anomalies occurring in lysyl oxidase down-regulated
      fibroblasts, related to beta-catenin signaling and cyclin D1 expression.

PMID- 15946753
TI  - G alpha selectivity and inhibitor function of the multiple GoLoco motif protein
      GPSM2/LGN.
AB  - GPSM2 (G-protein signalling modulator 2; also known as LGN or mammalian Pins) is
      a protein that regulates mitotic spindle organization and cell division. GPSM2
      contains seven tetratricopeptide repeats (TPR) and four Galpha(i/o)-Loco (GoLoco)
      motifs. GPSM2 has guanine nucleotide dissociation inhibitor (GDI) activity
      towards both Galpha(o)- and Galpha(i)-subunits; however, a systematic analysis of
      its individual GoLoco motifs has not been described. We analyzed each of the four
      individual GoLoco motifs from GPSM2, assessing their relative binding affinities
      and GDI potencies for Galpha(i1), Galpha(i2), and Galpha(i3) and Galpha(o). Each
      of the four GPSM2 GoLoco motifs (36-43 amino acids in length) was expressed in
      bacteria as a GST-fusion protein and purified to homogeneity. The binding of each
      of the four GST-GoLoco motifs to Galpha(i1)-, Galpha(o)-, and Galpha(s)-subunits
      was assessed by surface plasmon resonance; all of the motifs bound Galpha(i1),
      but exhibited low affinity towards Galpha(o). GDI activity was assessed by a
      fluorescence-based nucleotide-binding assay, revealing that all four GoLoco
      motifs are functional as GDIs for Galpha(i1), Galpha(i2), and Galpha(i3).
      Consistent with our binding studies, the GDI activity of GPSM2 GoLoco motifs on
      Galpha(o) was significantly lower than that toward Galpha(i1), suggesting that
      the in vivo targets of GPSM2 are most likely to be Galpha(i)-subunits.

PMID- 15946754
TI  - Further evidence of inflammation in chronic rheumatic valve disease (CRVD): high
      levels of advanced oxidation protein products (AOPP) and high sensitive C
      reactive protein (hs-CRP).
AB  - Chronic rheumatic valve disease (CRVD) is a late sequel of Rheumatic Fever (RF)
      which appears in approximately 30% of RF patients, leading to valve injury.
      Advanced Oxidation Protein Products (AOPP) and high sensitive C-Reactive Protein
      (hs-CRP) plasma levels were measured in patients with CRVD in order to evaluate
      the presence of oxidative stress and systemic inflammation. A total of 90
      patients (70 female, 20 male, mean age 46.01 +/- 11.72 years, range 24-69 years)
      with CRVD, who have or have not undergone valve replacement due to rheumatic
      etiology, and 46 healthy subjects (27 female, 19 male, mean age 41.89 +/- 9.02
      years range 28-60 years) were studied. Levels of AOPP were measured by the
      determination of optical density (OD) at 340 nm under acidic conditions and hs
      CRP by enhanced immunonephelometric assays. Significantly elevated levels of AOPP
      and hs-CRP were observed in CRVD patients when compared to the controls (AOPP
      212.62 +/- 34.14 umol/l vs. 126.97 +/- 27.74 umol/l p < 0.00006 and for hs-CRP
      5.40 +/- 1.98 mg/l vs. 2.66 +/- 1.36 mg/l p < 0.05). In addition, high levels of
      AOPP were associated to the presence of prosthetic valve and time after surgery
      (p < 0.0008 and p < 0.005, respectively). No correlation was observed between the
      levels of AOPP and hs-CRP with age, sex and degree of mitral valve stenosis. No
      correlation was found between AOPP and hs-CRP plasma values. These results
      suggest the involvement of oxidative stress and systemic inflammation in the
      pathogenesis of CRVD.

PMID- 15946755
TI  - Stability, reliability and consistency of the compositions of brain oscillations.
AB  - In the present experimental study, we examined the compositions of
      electroencephalographic (EEG) brain oscillations and their percent ratio in 12
      subjects during resting conditions (closed and open eyes) and during the memory
      task (waiting, encoding and keeping-in-mind stages). The exact compositions of
      brain oscillations and their percent ratio were assessed by the probability
      classification analysis of short-term EEG spectral patterns, which results in the
      probability-classification profile (PCP). Within sessions the PCPs are found to
      be stable, as reflected by a relatively low coefficient of variability, and
      between sessions the PCPs are highly reproducible. Finally, test-retest
      reliability of subject's PCPs shows a dependency on task, being higher for the
      memory task, and in particular for the encoding stage. It was suggested that
      these findings support and strengthen the superposition principle where
      integrative brain functions are manifested in the superposition of distributed
      multiple oscillations.

PMID- 15946756
TI  - Purification, kinetic and thermodynamic studies of a new ribonuclease from a
      mutant of Aspergillus niger.
AB  - Ribonuclease was purified from Aspergillus niger SA-13-20 to homogeneity level by
      using (NH(4))(2)SO(4) precipitation, DEAE-cellulose anion-exchange
      chromatography, ultrafiltration and Sephacryl HR-200 chromatography. The
      molecular weight and isoelectric point of the enzyme was 40.1kDa and 5.3,
      respectively. The pH- and temperature-dependent kinetic parameters were
      determined. The RNase showed the strongest affinity with RNA as the substrate,
      and the highest catalytic efficiency for hydrolysis of the substrate at pH 3.5
      and 65 degrees C. It exhibited Michaelis-Menten Kinetics with k(cat) of 118.1s(
      1) and K(m) of 57.0 microg ml(-1), respectively. Thermodynamic parameters for
      catalysis and thermal denaturation were also determined. Activation energy (E(a))
      for catalysis of A. niger SA-13-20 RNase was 50.31 kJ mol(-1) and free energy
      (DeltaG(#)), enthalpy (DeltaH(#)) and entropy (DeltaS(#)) of activation for
      catalysis of the enzyme at 65 degrees C were 69.76, 47.50 and -65.83 Jmol(-1)K(
      1), respectively. Activation energy (E(a,d)) for denaturation of the enzyme was
      200.53 kJ mol(-1) and free energy (DeltaG(d)(#)), enthalpy (DeltaH(d)(#)) and
      entropy (DeltaS(d)(#)) of activation for denaturation of the enzyme at 45 degrees
      C were 79.18 kJ mol(-1), 197.88 and 373.09 Jmol(-1)K(-1), respectively.

PMID- 15946757
TI  - Persistence of bluetongue virus serotype 2 (BTV-2) in the southeast United
      States.
AB  - The prototype United States (US) strains of bluetongue virus serotype 2 [BTV-2
      (OnaA) and BTV-2 (OnaB)] made in Florida in 1982 were compared to a recent BTV-2
      (FL99) isolate made in Florida in 1999 to determine if the original strain(s) had
      persisted or if a new strain of BTV-2 had been re-introduced into the southeast
      US. Viral RNA and protein electropherotypes, and sequence analysis of five RNA
      genome segments for these early and later BTV-2 isolates were compared. These
      comparisons indicated that BTV-2 (OnaB) has persisted in the southeast US since
      its first isolation in 1982. Sequence analysis of concurrent isolates of BTV-13
      (FL99) and BTV-17 (FL99) from the same location in Florida in 1999 provides
      evidence of genetic reassortment between BTV-2 and other co-circulating serotypes
      of BTV.

PMID- 15946758
TI  - Blends of aqueous polymer dispersions used for pellet coating: importance of the
      particle size.
AB  - Blends of aqueous dispersions of a water-insoluble and an enteric polymer, namely
      ethyl cellulose:hydroxypropyl methylcellulose acetate succinate (EC:HPMCAS) and
      ethyl cellulose:methacrylic acid ethyl acrylate copolymer (EC:Eudragit L), were
      used as coating materials to control theophylline release from matrix pellets.
      Varying the polymer blend ratio, broad ranges of drug release patterns were
      obtained at low as well as at high pH. Interestingly, the resulting release
      profiles were rather similar for both types of blends in 0.1 M HCl, whereas
      significant differences were observed in phosphate buffer pH 7.4. Surprisingly,
      drug release at high pH was much slower for EC:HPMCAS blends compared to
      EC:Eudragit L blends, although HPMCAS leached out more rapidly (and to a higher
      extent) from the film coatings than Eudragit L. To explain these phenomena and to
      better understand the underlying drug release mechanisms, thin polymeric films of
      identical composition as the pellet coatings were prepared and physicochemically
      characterized before and upon exposure to the release media. Importantly, the
      polymer particle size was identified to be a very crucial formulation parameter,
      determining the resulting film coating structure and properties. The Eudragit L
      particles are much smaller than the HPMCAS particles (nano- vs. micrometer size
      range) and, thus, more effectively hinder the formation of a continuous and
      mechanically stable EC network. Consequently, the EC structures remaining after
      enteric polymer leaching at high pH are mechanically much weaker in the case of
      Eudragit L. Upon exposure to phosphate buffer, water-filled cracks are formed,
      through which the drug rapidly diffuses out. In contrast, the EC structures
      remaining upon HPMCAS leaching are mechanically stronger and drug release is
      controlled by diffusion through the polymeric remnants.

PMID- 15946759
TI  - Prevalence of diabetes in rural Victoria.
AB  - AIMS: To compare the prevalence of diabetes in adults in small and medium sized
      towns in a part of rural Victoria MATERIALS AND METHODS: Participants were usual
      residents, aged >or=25 years, from randomly selected households in the crossroads
      undiagnosed disease study (CUDS: six small rural towns and their regional center
      in rural Victoria). Response rates to an initial census at the household and
      attendance at a subsequent biomedical examination involved were 70% and 61%
      (1454), respectively. All non-diabetic participants had an oral glucose tolerance
      test. RESULTS: Prevalence of diabetes, IGT, IFG were 7.3 (5.5-9.5)%, 6.9 (5.1
      9.9)% and 3.2 (2.0-4.7)% respectively in the regional center and 8.9 (6.9-11.1)%,
      4.9 (3.5-6.7)%, 3.0 (1.9-4.5)% in the Shire Capitals. Overall, 31/118 (26.3%) of
      those with diabetes were previously undiagnosed. Most (83.9%) of those with
      undiagnosed diabetes remembered having been screened for diabetes in the previous
      2 years. Overall screening rates for diabetes were higher than across Victoria as
      a whole. CONCLUSIONS: The prevalence of diabetes has probably doubled over the
      last 15 years in this area. Undiagnosed diabetes is less common than expected,
      possibly as a result of a more vigorous approach to screening in general practice
      and in spite of the lower numbers of GPs in the area.

PMID- 15946760
TI  - Clinical characteristics of Japanese youth-onset type 2 diabetes with ketonuria.
AB  - The study analyzed the clinical background and eating habits of Japanese youth
      onset type 2 diabetes. Thirty-six patients with type 2 diabetes (22 males, 14
      females) with onset in less than 20-year-old were studied. All patients were
      negative for anti-glutamic acid decarboxylase (GAD) antibody and islet cell
      antibody. Cases diagnosed as having abnormalities in the mitochondrial gene,
      maturity onset diabetes of the young (MODY), and apparent type 1 diabetes were
      excluded from the study. Urinary ketone was detected positive in 11 cases among
      36 patients at the onset of diabetes. We compared the clinical characteristics
      and food compositions between the patients with ketonuria and those without
      ketonuria. Age and urinary C-peptide secretion did not show any significant
      difference between both groups. In the patients with ketonuria, male to female
      ratio was remarkably high (10:1) compared with the group without ketonuria
      (12:13). Positive diabetic family history was predominantly higher in the group
      with ketonuria (11/11) than that in the group without ketonuria (17/25). All
      these were identical to previously reported characteristics of soft-drink
      ketosis. However, we in this study, revealed the difference of total calorie
      intake and dietary composition between youth-onset type 2 diabetes with and
      without ketonuria. As a result dietary contents such as carbohydrate, fat and
      confectionery in the former group were also 1.5, 1.4-2.4 times higher,
      respectively, than those in the latter group.

PMID- 15946761
TI  - Estimated prevalence of osteoporosis from a Nationwide Health Insurance database
      in Taiwan.
AB  - Approximately 9.24% of the Taiwanese population is aged 65 years or older. Among
      them, osteoporosis is a major problem, along with it associated age-related
      fractures. We investigated the prevalence of osteoporosis in 1996-2001 by
      sampling Taiwan's National Health Insurance (NHI) database. Data from 102,763 men
      (51.27%) and 97,654 women (48.73%) were evaluated. In this cohort, osteoporosis
      was recorded in each yearly dataset if the codes 733.0 or 733.00-733.09 were
      found on a search of the administrative or outpatient sub-databanks. A stable
      estimated prevalence of osteoporosis was calculated according to Taiwan's NHI
      sampling data from 1999 to 2001. The results showed a trend toward increasing
      proportions of coded osteoporosis with age, more predominantly in the female
      population. The averaged prevalence of osteoporosis, between 1999 and 2001, in
      those aged > or = 50 years was 1.63% for men and 11.35% for women. These
      estimates were lower than those reported elsewhere for Taiwan and for Japan but
      more equal to that in the Mexican American sub-population of the United States.
      In conclusion, the prevalence of osteoporosis is underestimated in the NHI
      database. Policymakers should be aware of this finding and allocate resources
      accordingly.

PMID- 15946762
TI  - Understanding consumers' preferences and decision to enrol in community-based
      health insurance in rural West Africa.
AB  - This paper presents a qualitative investigation of consumers' preferences
      regarding the single elements of a community-based health insurance (CBI) scheme
      recently implemented in a rural region in west Africa. The aim is to provide
      adequate policy-guidance to decision makers in low and middle income countries by
      producing an in-depth understanding of how consumers' preferences may affect
      decision to participate in such schemes. Although it has long been suggested that
      feeble levels of participation may very well be an expression of consumers'
      dissatisfaction with scheme design, little systematic efforts have so far been
      channelled towards supporting such argument with empirical evidence. Consumers'
      preferences were explored through means of 32 individual interviews with
      household heads. Analysis used the method of constant comparison and was
      conducted by two independent researchers. Data from 10 focus group discussions
      provided an additional valuable source of triangulation. Findings suggest that
      decision to enrol is closely linked to whether the single elements of the scheme
      match consumers' needs and expectations. In particular, consumers justified
      decision to join or not to join the insurance scheme in relation to their
      preference for the unit of enrolment, the premium level and the payment
      modalities, the benefit package, the health service provider network and the CBI
      managerial structure. The discussion of the findings focuses on how understanding
      consumers' preferences and incorporating them in the design of a CBI scheme may
      result in increased participation rates, ensuring that poor populations gain
      better access to health services and enjoy greater protection against the cost of
      illness.

PMID- 15946763
TI  - Adjusted Clinical Groups (ACGs) explain the utilization of primary care in Spain
      based on information registered in the medical records: a cross-sectional study.
AB  - BACKGROUND: Previous studies have shown the validity of Adjusted Clinical Groups
      (ACGs) in the primary care setting, but the absence of administrative databases
      is a problem for the implementation of this system. OBJECTIVES: To assess the
      validity of physicians' notes in computerized clinical records for the
      implementation of ACGs, and to determine the ability of the ACGs system to
      explain the use of primary care resources in real conditions of the daily
      practice. RESEARCH DESIGN: Cross-sectional study. SUBJECTS: All patients who were
      continuously assigned to 56 physicians from public primary health care centers in
      the Bizkaia Basque Country (Spain) over at least a 6-month period were included.
      MEASURES: Patients were classified by means of the ACGs system using the ICD-9-CM
      diagnostic codes according to three scenarios: (1) those annotated by the
      physicians in the computerized medical record, (2) codification of computerized
      medical records diagnoses by the research team, and (3) computerized medical
      records diagnoses complemented by hospital discharge codes. RESULTS: The ACGs
      system explained more than 50% of the variance in visits made to primary care
      physicians, 25-40% of prescriptions, 25-30% of referrals and requests of
      laboratory tests, and 14-16% of radiographs. The coefficients of determination
      remained almost invariable after the addition of hospital diagnoses or correction
      of coding errors. Fifty-two physicians (93%) registered their patients' diagnosis
      quite acceptably, whereas only 29 (52%) included this datum in the prescriptions.
      CONCLUSIONS: The ACGs system is a useful tool to explain the use of primary care
      services in a national health care system within the European Union. The
      implementation of ACGs from the physician's annotations in the computerized
      medical records is feasible.

PMID- 15946764
TI  - Sister chromatid cohesion along arms and at centromeres.
AB  - There is an obvious difference between the regulation of sister chromatid
      cohesion at centromeres and along chromosome arms during meiosis, because
      centromeric cohesion, but not arm cohesion, persists throughout anaphase of the
      first meiotic division. This regional difference of sister chromatid cohesion is
      also observed during mitosis; the cohesion is much more robust at the centromere
      at metaphase, where it antagonizes the pulling force of spindle microtubules that
      attach to the kinetochores from opposite poles. Recent studies have illuminated
      the underlying molecular mechanisms that strengthen and protect centromeric
      cohesion in mitosis and meiosis, and the central role of a conserved protein,
      shugoshin.

PMID- 15946765
TI  - A highly unexpected strong correlation between fixation probability of
      nonsynonymous mutations and mutation rate.
AB  - Under prevailing theories, the nonsynonymous-to-synonymous substitution ratio
      (i.e. K(a)/K(s)), which measures the fixation probability of nonsynonymous
      mutations, is correlated with the strength of selection. In this article, we
      report that K(a)/K(s) is also strongly correlated with the mutation rate as
      measured by K(s), and that this correlation appears to have a similar magnitude
      as the correlation between K(a)/K(s) and selective strength. This finding cannot
      be reconciled with current theories. It suggests that we should re-evaluate the
      current paradigms of coding-sequence evolution, and that the wide use of
      K(a)/K(s) as a measure of selective strength needs reassessment.

PMID- 15946766
TI  - Identification of a new RTN3 transcript, RTN3-A1, and its distribution in adult
      mouse brain.
AB  - The Reticulon (RTN) family of proteins is thought to play important roles in the
      regulation of neuronal regeneration. In this study, we have identified a novel
      alternative splicing isoform of the RTN gene family, RTN3-A1, which contains an
      additional 2.3-kb exon. The transcripts of human and mouse RTN3-A1 (about 5.0 kb)
      were first discovered by database sequence mining and analysis, and verified by
      cloning and sequencing. Northern blot analysis of 16 human tissues with a common
      probe of RTN3 transcripts and a specific probe for RTN3-A1 demonstrated that
      human RTN3-A1 is expressed mainly in brain tissues with a weak expression in the
      skeletal muscle. With Western blot analysis, the expected 100-kDa RTN3-A1 protein
      was detected in mouse brain. In situ hybridization with a mouse RTN3-A1-specific
      cRNA probe revealed that the mouse RTN3-A1 mRNA was regionally expressed in the
      neurons of the cerebral cortex, hippocampus, hypothalamus, and cerebellum of the
      adult mouse brain. In contrast to the transcripts of RTN1 and RTN2, RTN3-A1
      shares some significant similarity with RTN4-A in exon structure, tissue
      distribution, and brain expression profile. Since other reports have shown that
      RTN4-A inhibits neuronal outgrowth and restricts the plasticity of the central
      nervous system, we speculate that RTN3-A1 might play certain roles in the central
      nervous system.

PMID- 15946767
TI  - Food deprivation enhances the expression but not acquisition of flavor acceptance
      conditioning in rats.
AB  - The postingestive actions of nutrients condition strong flavor preferences in
      rats and may also enhance flavor acceptance (increase total intake) in some
      situations. This study determined the impact of food deprivation on flavor
      preference and acceptance conditioned by intragastric (i.g.) infusions of
      glucose. Rats fitted with gastric catheters were trained (20 h/day) to associate
      a CS+ solution (bitter or sour) with i.g. 16% glucose and a CS- solution with
      water infusions. One group (FR) was food-restricted during the training sessions,
      while a second group (AL) was given food ad libitum. All rats were given 2-h
      access to food prior to the daily sessions. During one-bottle training, the FR
      rats consumed substantially more CS+ than CS- whereas AL rats drank only slightly
      more CS+ than CS-. In additional one-bottle acceptance tests, the FR and AL rats
      consumed substantially more CS+ than CS- when both groups were food-restricted,
      but only slightly more CS+ than CS- when both groups had food ad libitum.
      Throughout the experiment, the FR and AL rats displayed equally strong CS+
      preferences in two-bottle choice tests irrespective of their deprivation state
      during the test. The findings indicate that food restriction stimulates the
      intake of a CS+ flavor that is (or was previously) paired with i.g. glucose
      infusions but does not fundamentally alter the learned association between the
      CS+ flavor and the post-oral nutrient stimulus.

PMID- 15946768
TI  - Incidence of surgical site infections and accompanying risk factors in Vietnamese
      orthopaedic patients.
AB  - A cohort study of surgical site infections (SSIs) was conducted in 582
      orthopaedic surgical patients at Cho Ray Hospital, a reference hospital in Ho Chi
      Minh City, Vietnam, in order to determine the incidence and analyse risk factors
      for SSIs in this population. The SSI incidence rate was 12.5% (73 of 582); 3.6%
      incisional SSIs, 6.8% deep incisional SSIs and 2.1% organ/space SSIs. The
      incidence increased from 2% in clean wounds to 44.6% in dirty wounds, or 1.3% in
      patients with a National Nosocomial Infections Surveillance (NNIS) risk index of
      0 to 75% in patients with an NNIS risk ratio of 3. In multi-variate analysis,
      having a dirty wound [odds ratio (OR) 8.7; 95% confidence intervals (CI) 4.6-
      16.4], American Society of Anesthesiologists' score >2 (OR 3.9; 95%CI 1.8-8.8),
      procedures with external fixation (OR 2.9; 95%CI 1.4-5.9), emergency surgery with
      motor-vehicle-related trauma (OR 2.1; 95%CI 1.2-3.9), or duration of procedure
      >2h (OR 2.1; 95%CI 1.1-4.2) were independent risk factors for SSI. Lack of
      appropriate prophylaxis was of borderline significance (OR 3.2; 95%CI 0.9-11.1,
      P=0.06). Among 76 patients with SSIs, 22 patients were discovered during
      postdischarge follow-up. These late SSIs had age as an additional risk factor (OR
      2.8; 95%CI 1.1-7.2). Our data show that SSIs were frequent and differed widely by
      wound class. The NNIS risk index was predictive of SSI for this population. With
      a high number of motor vehicle accidents in Vietnam, the majority of orthopaedic
      operations are trauma related. Emergency surgery for injuries sustained in these
      accidents, and procedures with external fixation were especially prone to
      infections.

PMID- 15946769
TI  - cDNA cloning of halocidin and a new antimicrobial peptide derived from the N
      terminus of Ci-META4.
AB  - Halocidin is an antimicrobial peptide, which is isolated from hemocytes from the
      tunicate, Halocynthiaaurantium. In this study, we cloned the full-length cDNA of
      halocidin from pharyngeal tissue, using a combination of RT-PCR and 5'-RACE-PCR.
      The observed cDNA structure indicated that halocidin is synthesized as a 10.37
      kDa prepropeptide. Based on the cDNA structure and the known amino acid sequence
      of the mature peptide, it was concluded that the precursor of halocidin contains
      a 21-residue signal peptide, followed by the 18 residues of the mature peptide,
      and a 56-residue anionic C-terminal extension, which is removed later on in the
      process. The signal sequence of halocidin exhibited a high degree of similarity
      with the corresponding portion of the Ci-META4 protein, which had been previously
      discovered in the coelomic cells of another tunicate, Cionaintestinalis, and is
      considered to play a role in metamorphosis. However, in several respects, the
      cDNA structure of Ci-META4 suggested that it might constitute a precursor for an
      antimicrobial peptide. Thus, we prepared a synthetic peptide, which was comprised
      of 19 N-terminal amino acid residues in the predicted mature region of Ci-META4,
      and tested it with regard to its antimicrobial activity. As a result, we
      confirmed that the synthetic peptide exhibited potent antimicrobial activity
      against Gram (+) and (-) bacteria, while evidencing no hemolytic activity toward
      human erythrocytes.

PMID- 15946770
TI  - Albumin peptide: a molecular marker for trauma/hemorrhagic-shock in rat
      mesenteric lymph.
AB  - Vascular permeability and endothelial cell damage has been shown to occur in rats
      subjected to trauma with hemorrhagic-shock. Although the factors responsible for
      the endothelial cell injury are unknown, it has been hypothesized that toxic
      factors produced in response to hemorrhagic-shock originate in the gut and are
      absorbed into the mesenteric lymphatics. Consistent with this hypothesis, it has
      been shown that lymph collected from animals subjected to trauma with hemorrhagic
      shock (T/HS) results in a marked decrease in endothelial cell viability both in
      vitro and in vivo. We therefore compared the lymph collected pre-T/HS to samples
      collected during, and up to 3h post-T/HS in order to identify a factor present or
      increased in post-T/HS lymph. This analysis revealed that a single cationic
      peptide band was significantly increased in post-T/HS lymph, but not in lymph
      from control animals subjected to trauma without hemorrhagic-shock (T/SS). This
      peptide was subsequently identified as the N-terminal 24 amino acids of rat serum
      albumin (RSA) by mass spectrometry and amino acid sequencing. Although the
      measured increase in the albumin peptide correlates with detectable shock lymph
      induced endothelial cell toxicity, the peptide was not toxic to endothelial
      cells. We therefore propose that the significant increase in the albumin peptide
      is a marker for post-T/HS lymph-induced endothelial cell toxicity.

PMID- 15946771
TI  - Effect of amino acid substitutions on the candidacidal activity of LFampin 265
      284.
AB  - LFampin 265-284, derived from bovine lactoferrin, has broad-spectrum
      antimicrobial activity against the yeast Candida albicans and several Gram
      positive and Gram-negative bacteria. A glycine substitution scan was used to
      identify residues that are important for its candidacidal activity. Each single
      substitution of a positively charged residue led to considerable reduction in
      candidacidal activity, for each residue to a different extent. Substitution
      within the helix-facilitating N-terminal sequence DLIW had less severe effect;
      substitution of Ile and Trp led to a somewhat reduced potency. No substantial
      effects were found on the propensity to adopt a helical structure or to bind to
      C. albicans cells.

PMID- 15946772
TI  - Biophysical and biochemical characterization of the intrinsic fluorescence from
      neurofibrillary tangles.
AB  - Recently, we developed a novel fluorescent method named intrinsic fluorescence
      induction that allows direct visualization of neurofibrillary pathology without
      introducing exogenous chromogens. In the present study, we further characterized
      the properties of this novel red fluorescence biophysically, biochemically, and
      neuropathologically. In vitro spectrofluorometry and in situ emission scan show
      that the intrinsic fluorescence of neurofibrillary tangles has a long emission
      wavelength peak at 620 nm and a large Stoke's shift of 70 nm. Dephosphorylation
      of Alzheimer's disease brain sections with alkaline phosphatase or denaturation
      with guanidine only causes a subtle reduction in the induced fluorescence of
      neurofibrillary tangles, while hydrofluoric acid or formic acid completely
      eliminates the fluorescence. Chemical modification of residue serine, but not
      tyrosine or tryptophan, reduced the intensity of induced fluorescence
      significantly. The induced fluorophore, thus, has unique properties, and its
      generation likely depends on the particular conformation of paired helical
      filaments, which may in turn depend on tau hyperphosphorylation.

PMID- 15946773
TI  - [Isolated pseudo-tumoral tuberculosis of the spleen. A case report].
AB  - INTRODUCTION: The tuberculosis isolated tumoral spleen is rare, even in the
      countries to strong tubercular endemic. EXEGESIS: From an observation, concerning
      an important, tumoral and isolated splenomegaly in 48-year-old-man. The authors
      put the accent on his tumorous variety by the clinic, the imagery and on
      macroscopic appearance of the operative piece. Are discussed the isolated
      character, the way of dissemination, the site of initial infestation and the
      deceitful character of haematological manifestations. A splenectomy to diagnostic
      and therapeutic goal have been realised, associated to the chemotherapy.
      CONCLUSION: This is an expression of the profound organ's tuberculosis rich on
      endothelial reticular system. It's mean a singular topography of the bacillary
      lesion and a great distribution of the tubercular affect.

PMID- 15946774
TI  - [Tuberculosis peritonitis: an always present disease. About 4 new cases].
AB  - INTRODUCTION: Tuberculous peritonitis, a major problem in developing country,
      occurs preferentially in immigrant population and in patients with acquired
      immune deficiency syndrome (AIDS). Although rare in France, it did not disappear
      and epidemiological, clinical and therapeutic approach deserve to be reminded.
      EXEGESIS: We reported 4 patients (immigrants in two cases), occurred in caucasian
      and African persons (one with AIDS). Disease was characterized by fever,
      abdominal pain, anorexia, weight loss and ascites. Biological and radiological
      were unconclusive. Cell count analysis from ascitic fluid show a lymphocytic
      predominance with negative direct smear for Ziehl-Neelsen strain. Tuberculous
      peritonitis was established with combined visual and histological diagnosic
      laparoscopic examination. CONCLUSION: These observations have the interest to
      underline that tuberculous peritonitis must be evoked in case of lymphocytic
      ascitis. We believe an aggressive diagnostic approach, particulary with
      peritoneal biopsy, is warranted for the diagnosis of tuberculous peritonitis.
      Validity of PCR amplification is ascitic fluid still needs to be established.

PMID- 15946775
TI  - The nutritional knowledge of Australian nurses.
AB  - Sound nutrition is an essential component of good health. A number of health
      professionals, including nurses, provide nutritional information to the
      community. However, little research exists which measures the nutrition knowledge
      of nurses in Australia. The aim of this study was to determine the nutrition
      knowledge of nurses in regional Victoria. A descriptive cross-sectional study
      design was used with 103 nurses (81% currently practicing in an acute regional
      hospital). The nurses answered 48 multiple choice general knowledge questions
      (using a valid and reliable questionnaire) and provided educational and
      demographic details. Each multiple choice question was scored as correct or
      incorrect and given the value of one point (maximum possible 48 points). The mean
      knowledge score for all nurses was 60.2% (SD = 8.4). Older nurses, those with
      more years of experience, and nurses with general training (rather than a degree)
      scored higher average knowledge scores. Respondents reported requests for
      nutrition information from patients and clients, and indicated that the most
      frequently used nutrition information sources were dietitians, other nurses,
      professional journals, books and literature from the National Heart Foundation.
      The nutrition knowledge score reported in this study is low to moderate by
      definition from previous studies using the same questionnaire. It is recommended
      that the Australian nursing profession determines its own nutrition knowledge
      standard and the nutrition knowledge needs of nurses working in particular areas
      of practice. Further work is required to determine the validity and reliability
      of an Australian knowledge instrument.

PMID- 15946776
TI  - The co-administrating of recombinant porcine IL-2 could enhance protective immune
      responses to PRV inactivated vaccine in pigs.
AB  - Three candidate cytokines: recombinant porcine interleukin-2 (rpIL-2), rpIL-6 and
      the fusion protein rpIL6-IL2 were used as adjuvants in this study to investigate
      the enhanced immune responses to PRV inactivated vaccine (IAV) in pigs. In this
      natural host trial, we demonstrated that rpIL-2 showed potential adjuvant effects
      on PRV IAV, which was characterized not only in antigen-specific immune
      responses, but also in protection against PRV infection. The use of rpIL-2
      resulted in significantly higher virus neutralizing (VN) antibody levels and CTL
      activities on PRV IAV vaccination. The increased PRV-specific secretion of pIL-4
      and pIFN-gamma from PBMC of pigs also demonstrated the adjuvant effects of rpIL
      2. In addition, the co-administration of the rpIL-2 also produced an improved
      protection to the viral challenge, demonstrated by significant reduction of the
      ratios of fever and viral excretion in nasal swabs. However, there was no
      additional effect of adjuvant induced enhancement of immune responses and
      protection against challenge with the use of rpIL-6 and rpIL6-IL2 in this study.

PMID- 15946777
TI  - Congenital double lip: review of 5 cases.
AB  - Congenital double lip is rare and usually involves the upper lip. Apart from a
      deformity that interferes with speech and mastication, operation may be indicated
      for cosmetic reasons. We have operated on five patients with double lip
      deformities for cosmetic reasons. Although a midline constriction band between
      two mucosal bulges is thought to be a constant feature, four of our five cases
      did not have a midline constriction. We used an elliptical excision of the
      mucosal excess in the four patients. The one with central constriction had an
      elliptical excision on each side, combined with a vertical midline Z-plasty to
      release the central constriction. Satisfactory aesthetic results were achieved in
      all patients.

PMID- 15946778
TI  - Treatment of recurrent odontogenic keratocyst: a known but forgotten point.

PMID- 15946779
TI  - Beyond the HLA typing age: genetic polymorphisms predicting transplant outcome.
AB  - Although histocompatibility testing and matching for histocompatibility leukocyte
      antigens (HLA) remains the "state of the art" for determining donor selection,
      non-HLA encoded genes such as those for minor histocompatibiity antigens also
      play an important role in determining haematopoietic stem cell transplantation
      (HSCT) outcome. Single nucleotide polymorphisms (SNPs) within the promoter
      regulatory regions of non-HLA encoded genes such as those for cytokines and
      cytokine receptors which regulate the production of such molecules may also play
      a role in determining the extent of post-transplant complications. Mannose
      binding lectin genes (MBL) and other genes such as those for myeloperoxidase
      (MPO) and Fcgamma receptor may aid in the control of infection post transplant.
      This review will summarise the latest research concerning this area of predicting
      HSCT outcome and indicate the potential clinical use of the results.

PMID- 15946780
TI  - New drug targets in the signaling pathways activated by antidepressants.
AB  - Studies of twins, genetic linkage and association support the existence of a
      genetic component to the susceptibility to depression. Biochemical parameters
      that change in depressive patients are also observed in their relatives. This
      indicates that genetic factors control these physiological changes and the
      susceptibility to depression. The study of the mechanisms by which different
      genetic factors affect the organism's response to drugs can identify better
      diagnostic tools as well as drug targets. Pharmacogenomics can, therefore, help
      to find the most efficacious treatment for patients with specific genetic
      profiles. However, the genetic factors that determine the susceptibility to
      depression and the different responses to antidepressant treatment are largely
      unknown. Pharmacogenetic studies have used three different categories of genes to
      search for associations with the outcome of drug treatments. These gene
      categories are drug-metabolizing enzymes, known drug targets and known
      susceptibility genes. The present review will explore the different signal
      transduction pathways involved in antidepressant action and their possible use in
      psychopharmacogenomics and drug discovery.

PMID- 15946781
TI  - Investigating responders to lithium prophylaxis as a strategy for mapping
      susceptibility genes for bipolar disorder.
AB  - Attempts to map susceptibility genes for bipolar disorder have been complicated
      by genetic complexity of the illness and, above all by heterogeneity. This paper
      reviews the genetic research of bipolar disorder aiming to reduce the
      heterogeneity by focusing on definite responders to long-term lithium treatment.
      The available evidence strongly suggests that lithium-responsive bipolar disorder
      is the core bipolar phenotype, characterized by a more prominent role of genetic
      factors. Responders to lithium have typically a family history of bipolar
      disorder (often responsive to lithium). They differ from responders to other mood
      stabilizing drugs in their family histories as well as in other clinical
      characteristics. The molecular genetic investigations of bipolar disorder
      responsive to lithium indicate possibly several loci linked to and/or associated
      with the illness. A combination of research strategies employing multiple methods
      such as linkage, association, and gene-expression studies will be needed to
      clarify which of these represent true susceptibility loci.

PMID- 15946782
TI  - [Risk estimation in aesthetic surgery: a national study in French].
AB  - AIM: The aim of this study was to establish the status of the means of
      information and to search for the variability in risk estimation. MATERIALS AND
      METHODS: A questionnaire has been mailed to a hundred plastic surgeons randomly
      sorted among the habilitation list to be returned in an anonymous enclosed
      envelope. This random sample comprised 50 liberal practioners and 50 plastic
      surgeons working at hospital. The first part of this questionnaire dealed with
      basic data such as the type of activity (reconstructive or aesthetic), years of
      experience and means of information. The second part dealed in seven items with
      the most important preoperative information to be given to the patient and the
      most feared complications according to each surgeon before a reduction
      mammaplasty and abdominoplasty. RESULTS: A total of 50 (50%) of the 100
      questionnaires were returned. Years of experience influenced significantly the
      importance given to information and the way of transmitting it. Important
      variability existed between the surgeons' answers. Moreover, current
      complications were in many cases never mentioned. Risk estimation depended on the
      experience of the surgeon and the information procedures were influenced by the
      surgeon's type of activity. CONCLUSION: Important variability in risk estimation
      exists among the plastic surgeons leading to an important variability in the kind
      and way of delivering information.

PMID- 15946783
TI  - Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress
      in rats.
AB  - The aim of this study was to investigate the effects of lycopene on cisplatin
      induced nephrotoxicity and oxidative stress in rats. Adult male Sprague-Dawley
      rats were randomly divided into four groups. The control group (group 1) received
      physiological saline; animals in group 2 received only cisplatin; a 10 days of
      lycopene pre-treatment was applied to the animals in group 3 before
      administration of cisplatin; a 5 days of lycopene treatment was performed
      following administration of cisplatin for the animals in group 4. Cisplatin (7
      mg/kg) was intraperitoneally injected as a single dose and lycopene (4 mg/kg) was
      administered by gavage in corn oil. Biochemical and histopathological methods
      were utilised for evaluation of the nephrotoxicity. The concentrations of
      creatinine, urea, Na+ and K+ in plasma and levels of malondialdehyde and reduced
      glutathione as well as glutathione peroxidase and catalase activities were
      determined in kidney tissue. Administration of cisplatin to rats induced a marked
      renal failure, characterized with a significant increase in plasma creatinine and
      urea concentrations. Na+ and K+ levels of rats received cisplatin alone were not
      significantly different compared to control group, but they had higher kidney
      malondialdehyde, and lower reduce glutathione concentrations, glutathione
      peroxidase and catalase activities. Lycopene administration produced amelioration
      in biochemical indices of nephrotoxicity in both plasma and kidney tissues when
      compared to group 2; pre-treatment with lycopene being more effective. Results
      from this study indicate that the novel natural antioxidant lycopene might have
      protective effect against cisplatin-induced nephrotoxicity and oxidative stress
      in rat.

PMID- 15946784
TI  - Association between maternal panic disorders and pregnancy complications and
      delivery outcomes.
AB  - BACKGROUND: The objective of the study was to evaluate the possible association
      between panic disorders during pregnancy and pregnancy complications, as well as
      birth outcomes: gestational age and birth weight, as well as preterm birth/low
      birthweight in newborns. METHODOLOGY: Comparison of newborn infants (without any
      defects) born to mothers with or without panic disorder in the population-based
      large data set of the Hungarian Case-Control Surveillance System of Congenital
      Abnormalities. Main outcome measures were medically recorded pregnancy
      complications, as well as gestational age and birth weight, proportion of preterm
      birth and low birthweight. PRINCIPAL FINDINGS: Of 38,151 controls, 187 (0.5%) had
      mothers with panic disorders during pregnancy. Among pregnancy complications,
      anemia and polyhydramnion showed a higher prevalence in women with panic
      disorder. There was a higher proportion of males among newborn infants born to
      mothers with panic diseases compared to newborn infants of mothers without panic
      disorders. Pregnant women with panic disorders had a shorter (0.4 week)
      gestational age (adjusted t = 2.3; p = 0.02) and a larger proportion of preterm
      births (17.1% versus 9.1%) (adjusted POR with 95% CI = 1.9, 1.3-2.8). However,
      there was no significant difference in the mean birth weight and rate of low
      birthweight between the two study groups. CONCLUSION: Panic disorders during
      pregnancy were associated with anemia, a shorter gestational age and a larger
      proportion of preterm birth. Further studies are needed to confirm and explain or
      disprove the male excess among newborn infants born to mothers with panic
      disorders.

PMID- 15946785
TI  - The use of virtual environments for percentage view analysis.
AB  - It is recognised that Visual Impact Assessment (VIA), unlike many other aspects
      of Environmental Impact Assessments (EIA), relies less upon measurement than upon
      experience and judgement. Hence, it is necessary for a more structured and
      consistent approach towards VIA, reducing the amount of bias and subjectivity.
      For proposed developments, there are very few quantitative techniques for the
      evaluation of visibility, and these existing methods can be highly inaccurate and
      time consuming. Percentage view changes are one of the few quantitative
      techniques, and the use of computer technology can reduce the inaccuracy and the
      time spent evaluating the visibility of either existing or proposed developments.
      For over 10 years, research work undertaken by the authors at the University of
      Nottingham has employed Computer Graphics (CG) and Virtual Reality (VR) in
      civilian and industrial contexts for environmental planning, design
      visualisation, accident reconstruction, risk analysis, data visualisation and
      training simulators. This paper describes a method to quantitatively assess the
      visual impact of proposed developments on the landscape using CG techniques. This
      method allows the determination of accurate percentage view changes with the use
      of a computer-generated model of the environment and the application of
      specialist software that has been developed at the University of Nottingham. The
      principles are easy to understand and therefore planners, authorisation agencies
      and members of the public can use and understand the results. A case study is
      shown to demonstrate the application and the capabilities of the technology.

PMID- 15946786
TI  - Modelling of geochemical reactions and experimental cation exchange in MX 80
      bentonite.
AB  - Bentonites are widely used for waste repository systems because of their
      hydrodynamic, surface and chemical-retention properties. MX 80 bentonite
      (bentonite of Wyoming) contains approximately 85% Na/Ca-montmorillonite and 15%
      accessory minerals. The dominant presence of Na/Ca-montmorillonite in this clay
      mineral could cause it to perform exceptionally well as an engineered barrier for
      a radioactive waste repository because this buffer material is expected to fill
      up by swelling the void between canisters containing waste and the surrounding
      ground. However, the Na/Ca-montmorillonite could be transformed to other clay
      minerals as a function of time under repository conditions. Previous modelling
      studies based on the hydrolysis reactions have shown that the Na/Ca
      montmorillonite-to-Ca-montmorillonite conversion is the most significant chemical
      transformation. In fact, this chemical process appears to be a simple cation
      exchange into the engineered barrier. The purpose of the present study was two
      fold. Firstly, it was hoped to predict the newly formed products of bentonite
      fluid reactions under repository conditions by applying a thermokinetic
      hydrochemical code (KIRMAT: Kinetic Reactions and Mass Transport). The system
      modelled herein was considered to consist of a 1-m thick zone of water-saturated
      engineered barrier. This non-equilibrated system was placed in contact with a
      geological fluid on one side, which was then allowed to diffuse into the barrier,
      while the other side was kept in contact with iron-charged water. Reducing
      initial conditions ( [P(O)2 approximately equals 0] ; Eh=-200 mV) and a constant
      reaction temperature (100 degrees C) were considered. Secondly, it was hoped to
      estimate the influence of inter-layer cations (Ca and Na) on the swelling
      behaviour of the MX 80 bentonite by using an isothermal system of water vapour
      adsorption and an environmental scanning electron microscope (ESEM) coupled with
      a digital image analysis (DIA) program. Here, the MX 80 bentonite was previously
      treated with concentrated solutions (1N) of calcium and sodium chlorides. The
      results confirmed that the Na/Ca-montmorillonite-to-Ca-montmorillonite conversion
      was the main chemical transformation in the bentonite barrier under repository
      conditions. A simplified method (based on volume balance) has shown that the
      swelling capacity of the engineered barrier would be slightly affected after 1000
      years of diffusion-reaction because the volume of neo-formed swelling clays is
      almost directly proportional to the volume of transformed initial
      montmorillonite. Minimal neo-formation of saponites, vermiculites and chlorites
      was also observed. In addition, an isothermal system of water adsorption and ESEM
      DIA methods showed that in the raw-bentonite-to-Ca-bentonite exchange there is a
      small decrease in the amount of adsorbed water and the swelling potential.

PMID- 15946787
TI  - Explaining landholders' decisions about riparian zone management: the role of
      behavioural, normative, and control beliefs.
AB  - Water quality is a key concern in the current global environment, with the need
      to promote practices that help to protect water quality, such as riparian zone
      management, being paramount. The present study used the theory of planned
      behaviour as a framework for understanding how beliefs influence decisions about
      riparian zone management. Respondents completed a survey that assessed their
      behavioural, normative, and control beliefs in relation to intentions to manage
      riparian zones on their property. The results of the study showed that, overall,
      landholders with strong intentions to manage their riparian zones differed
      significantly in terms of their beliefs compared to landholders who had weak
      intentions to manage their riparian zones. Strong intentions to manage riparian
      zones were associated with a favourable cost-benefit analysis, greater
      perceptions of normative support for the practice and lower perceptions of the
      extent to which barriers would impede management of riparian zones. It was also
      evident that willingness to comply with the recommendations of salient referents,
      beliefs about the benefits of riparian zone management and perceptions of the
      extent to which barriers would impede riparian zone management were most
      important for determining intentions to manage riparian zones. Implications for
      policy and extension practice are discussed.

PMID- 15946788
TI  - Assessing pollution levels in sediments of a harbour with two opposing entrances:
      environmental implications.
AB  - The harbour of Ceuta, North Africa, differs substantially from conventional
      harbours with only one entrance since it has two opposing entrances and a channel
      which increases water renewal and local currents, with implications for
      sedimentary processes, levels of pollution and oxygen concentration. The
      distribution of heavy metals, nutrients and total hydrocarbons was investigated
      in sediment samples from this particular harbour. The grain size effect, a
      normalization technique using Fe concentrations and different sediment quality
      guidelines are discussed, and the data from the harbour of Ceuta are compared
      with other harbours worldwide. In spite of the water renewal, sediments inside
      the harbour of Ceuta were characterised by moderate levels of pollution, mainly
      hydrocarbons (496--6972 microg/g), P (282--1350 microg/g), N (100--2600 microg/g)
      and heavy metals Cu (5--865 microg/g), Pb (10--516 microg/g), Zn (296--695
      microg/g), Cr (13--381 microg/g) and Ni (8--671 microg/g). Taking into account
      that there is no industrial activity around the harbour of Ceuta, the major
      sources of contamination are the sewage effluents of urban influence, anti
      fouling paints and accidental oil spills during loading and dumping involved in
      shipping operations. The design of Ceuta harbour should be taken into
      consideration in the design, construction and management of future harbours.

PMID- 15946789
TI  - Status and fuzzy comprehensive assessment of combined heavy metal and organo
      chlorine pesticide pollution in the Taihu Lake region of China.
AB  - The status of combined heavy metal and organo-chlorine pesticide (OCPs; i.e. HCH
      and DDT) pollution was investigated and the soil environmental quality of the
      Taihu Lake watershed, one of the most developed regions in China, was evaluated
      using a fuzzy comprehensive assessment. Statistical analyses showed the presence
      of combined pollution in the soil. At many sampling sites, heavy metal
      concentrations were above corresponding background values, indicating the effects
      of extraneous pollutants. It has been over 20 years since China banned the use of
      OCPs, but they can still be found in soil samples of this region. HCH levels at
      all investigated sites were below the Chinese Environmental Quality Standard for
      Soils. Fuzzy comprehensive assessment showed that the overall soil quality in
      this region could be categorized as class I. Nevertheless, the high coefficients
      of variation for levels of DDT, Cd and Hg indicated the existence of some point
      source pollution. Continuous monitoring and further studies of the region are
      recommended to prevent pollution of farmland from these sources.

PMID- 15946790
TI  - On Myosin II dynamics in the presence of external loads.
AB  - We address the controversial hot question concerning the validity of the loose
      coupling versus the lever-arm theories in the actomyosin dynamics by re
      interpreting and extending the phenomenological washboard potential model
      proposed by some of us in a previous paper. In this new model a Brownian motion
      harnessing thermal energy is assumed to co-exist with the deterministic swing of
      the lever-arm, to yield an excellent fit of the set of data obtained by some of
      us on the sliding of Myosin II heads on immobilized actin filaments under various
      load conditions. Our theoretical arguments are complemented by accurate numerical
      simulations, and the robustness of the model is tested via different choices of
      parameters and potential profiles.

PMID- 15946791
TI  - Spinal cord ganglioglioma presenting as acute paraparesis.
AB  - A 17-year-old male presented with acute onset paraparesis in the lower limbs.
      Urinary retention was present and the patient required catheterisation. Clinical
      examination confirmed severe bilateral lower limb weakness and a sensory level at
      T8. Magnetic resonance imaging (MRI) revealed a haemorrhagic intramedullary
      tumour extending from T8 to the conus. Microsurgical excision of the tumour was
      performed and the patient made a good functional recovery. The histology of the
      tumour demonstrated a ganglioglioma of the spinal cord. Acute paraparesis has not
      previously been reported with a spinal cord ganglioglioma. We discuss the
      clinical, diagnostic and pathological features of spinal cord gangliogliomas.

PMID- 15946792
TI  - A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in
      human breast cancer expressing estrogen or progesterone receptors.
AB  - In contrast to the long-held belief that breast cancer is a weakly immunogenic
      tumor, accumulating evidence indicates an immune infiltrate is an invariable
      finding in breast cancers, raising hopes that immunotherapy for breast cancers
      may succeed in targeted patients, specifically those with either regional or
      minimal residual disease. However, no immunologically related prognostic factor
      has yet been established that may help to define subsets of patients who are more
      prone to respond to immunotherapy. High levels of soluble LAG-3 protein (sLAG-3)
      in sera has previously been shown to be associated, as a Th1 marker, to
      resistance to tuberculosis in large series of patients. We therefore hypothesized
      that, if cell-mediated immune mechanisms are indeed important for improved
      prognosis, high levels of sLAG-3 might be correlated with improved survival in
      some subsets of breast cancer patients. Studying a cohort of 246 patient's sera
      collected in 1994 at time of first diagnosis, we found that both disease-free and
      overall survival rates were greater in patients with estrogen or progesterone
      receptor positive tumor cells who had detectable levels of sLAG-3 at diagnosis
      versus patients with undetectable sLAG-3 levels. These results indicate that sLAG
      3 may be a valuable marker for prognosis in some subsets of breast cancers and,
      more importantly, that cell-mediated mechanisms such as Th1 responses do have an
      impact on survival, a pre-requisite before the setting-up of immunotherapy
      protocols as a form of adjuvant therapy for breast cancer.

PMID- 15946793
TI  - Inhibition of PhIP-induced mammary carcinogenesis in female rats by ingestion of
      freeze-dried beer.
AB  - This study evaluated the modulating effect of non-alcoholic constituents of beer
      on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary
      carcinogenesis. Female Sprague-Dawley (SD) rats at 6 weeks of age were divided
      into four groups (n=26-30) and fed either a high fat diet or high fat diets
      containing 1, 2 or 4% freeze-dried beer (FD beer). One week after the start of
      feeding, rats received PhIP at a dose of 85 mg/kg by gavage four times weekly for
      2 weeks. There were no differences in the body weights or diet intakes of rats
      between the control and the experimental groups. Weekly observation of palpable
      tumors indicated that tumor incidence and tumor multiplicity in the 2 and 4% FD
      beer groups were lower than in the control group throughout the experiment.
      Neoplastic lesions were pathologically examined at the end of the 22-weeks
      experiment. Tumor development was inhibited by FD beer intake in a dose-dependent
      manner. Tumor incidence (38.5%) and tumor multiplicity (0.8+/-0.4) for the group
      fed with a diet containing 4% FD were significantly reduced as compared with the
      control group (73.3% and 1.8+/-0.7). Supplementation with FD beer for 3 weeks
      together with the PhIP treatments resulted in increased liver GST activity,
      decreased liver CYP1A2 activity and a decrease in the number of DNA adducts in
      the mammary tissue, though these values were not significant. In conclusion, our
      results suggest that intake of FD beer may reduce the risk of carcinogenesis
      caused by heterocyclic amines.

PMID- 15946794
TI  - Proton magnetic resonance spectroscopy in neuroblastoma: current status,
      prospects and limitations.
AB  - Non-invasive biological information about residual neuroblastoma tumour tissue
      could allow treatment monitoring without the need for repeated biopsies. Magnetic
      resonance spectroscopy (MRS) can be performed with standard MR-scanners,
      providing specific biochemical information from selected tumour regions. By
      proton 1H-MRS, lipids, certain amino acids and lactate can be detected and their
      relative concentrations estimated in vivo. Using experimental models of
      neuroblastoma, we have described the potential of 1H-MRS for the prediction of
      tumour tissue viability and treatment response. Whereas viable neuroblastoma
      tissue is dominated by the choline 1H-MRS resonance, cell death as a consequence
      of spontaneous necrosis or successful treatment with chemotherapy, angiogenesis
      inhibitors, or NSAIDs is associated with decreased choline content. Therapy
      induced neuroblastoma cell death is also associated with enhanced 1H-MRS
      resonances from mobile lipids and polyunsaturated fatty acids. The mobile
      lipid/choline ratio correlates significantly with cell death and based on the
      dynamics of this ratio tumour regression or continued growth (drug resistance)
      after chemotherapy can be predicted in vivo. The implications of these findings
      are discussed with focus on the potentials and limitations of introducing 1H-MRS
      for clinical assessment of treatment response in children with neuroblastoma.
      Biochemical monitoring of neuroblastoma with 1H-MRS could enable tailoring of
      individual therapy as well as provide early pharmacodynamic evaluation of novel
      therapeutic modalities.

PMID- 15946795
TI  - GPX Pro198Leu and OGG1 Ser326Cys polymorphisms and risk of development of
      colorectal adenomas and colorectal cancer.
AB  - Little is known about genetic risk factors for colorectal cancer. We assessed the
      association between polymorphisms in two genes involved in DNA repair of
      oxidative stress, GPX and OGG1, and risk of colorectal carcinoma or adenomas. We
      studied 166 cases with adenocarcinoma, 974 with adenomas and 397 controls
      recruited from the Norwegian cohort NORCCAP. No associations were found between
      the polymorphism GPX Pro198Leu and risk of colorectal adenomas or carcinomas.
      Carriers of the variant allele OGG1 Ser326Cys polymorphism had a lowered risk of
      colorectal cancer, OR=0.56 (95% confidence interval 0.33-0.95), while no
      association were found with risk of adenomas. This indicates that a low repair
      capacity of oxidative DNA damage may not be a risk factor for development of
      colorectal adenomas or carcinoma.

PMID- 15946796
TI  - Gastric DNA damage through tobacco chewing: in vitro mechanistic studies of DNA
      nitrite attack.
AB  - Smokeless chewing tobacco or snuff has been linked to carcinogenic effects in
      upper aerodigestive organs. The presence of nitrite within the tobacco product is
      suspected to foster carcinogenic DNA mechanisms at lower pH. We studied the
      impact of sodium nitrite on DNA damage at single-strand conformers or hairpin
      loops, known to be present at fragile sites that have been shown to cause
      methyltransferase stalling and that can lead to chromosomal breakage. At a pH of
      4.2, two base-damage products could be demonstrated at significant levels (1-5%
      of total nucleotides), with greater sensitivity to hairpin loops compared to a
      control Watson-Crick duplex. Pyrimidine-rich strands (CCG, CTG) were more
      reactive than purine-rich strands (CAG, CGG). The data support a mechanism for
      allele-specific predisposition to DNA damage. This mechanism may be of
      significance in gastric cancer initiation due to chewing tobacco.

PMID- 15946797
TI  - Radiosensitization of tumours by porphyrins.
AB  - Our previous data indicate, that hematoporphyrin dimethyl ether (HPde) can
      totally inhibit the growth of aggressive Ehrlich ascite tumour, when combined
      with low doses (2Gy) of ionizing radiation. Taking into account these findings,
      it appears of particular interest to evaluate the dependence of radiosensitizing
      efficiency of porphyrins on tumour aggressiveness. For this purpose two
      experimental tumour models (aggressive murine Ehrlich ascite carcinoma, (EAT),
      and not-aggressive hepatoma MH-22A) were used. Moreover, radiosensitizing
      properties of three porphyrin-type compounds of different chemical heterogeneity
      were evaluated (hematoporphyrin dimethyl ether (HPde), photofrin II (PII) and
      hematoporphyrin derivative (HPD)). Data obtained indicate, that HPde is the most
      effective one in this context (HPde>PII>HPD). It is important to note, that only
      the aggressive EAT tumours were radiosensitized by these dyes. No signs of
      radiosensitization (inhibition of tumour growth, injury of tumour tissue,
      evaluated by histological analysis) were observed in not-aggressive MH-22A
      hepatoma. Moreover, it was shown, that ligands of peripheral benzodiazepine
      receptors (PBR) might diminish the cell growth in aggressive EAT, but not in not
      aggressive MH-22A hepatoma. The mechanism of radiosensitization by porphyrins,
      proposed in our previous studies, was strongly confirmed by these data. Actually,
      dicarboxylic porphyrins, being ligands of PBR, which are highly expressed in just
      aggressive tumours, can inhibit tumour cell proliferation and act in concert with
      ionizing radiation. Thus, combination of porphyrin and ionising radiation
      reflects the action of two antiproliferative factors, what eventually increases
      the response of aggressive tumours to the low doses of ionising radiation.

PMID- 15946798
TI  - Degradation of response modulation of visual cortical cells in cats with chronic
      exposure to morphine.
AB  - The primary visual cortex (V1) plays an important role in vision and visual
      perception. Studies in many brain regions demonstrate that opiate abuse can
      change excitatory and inhibitory neurotransmission. To investigate the effect of
      chronic morphine exposure on the response modulation of V1 simple and complex
      neurons, we carried out in vivo extracellular recordings in V1 of morphine- and
      saline-treated (control) cats. Response modulation was quantified as the ratio of
      first Fourier components (F1) to the mean response (F0). Compared with saline
      treated cats, V1 neurons in morphine-treated cats exhibited weaker response
      modulation and a longer time course of response. The decrease of response
      modulation was caused by an increase of F0. Further, morphine re-exposure
      significantly improved the response properties of V1 neurons in morphine-treated
      cats. These results suggest that chronic morphine treatment leads to a
      significant degradation of response modulation of V1 neurons and a morphine
      dependence of primary visual cortical function.

PMID- 15946799
TI  - Characterization of a novel vaccine candidate and serine proteinase inhibitor
      from Schistosoma japonicum (Sj serpin).
AB  - Serine proteinase inhibitors (serpins) represent an important superfamily of
      endogenous inhibitors that regulate proteolytic events active in a variety of
      physiological functions. Immunological screening of a Schistosoma japonicum adult
      worm cDNA expression library with sera of Microtus fortis, a naturally resistant
      vertebrate host, has identified one clone that encoded for a sequence homologous
      to those of the serpin superfamily. The full-length sequence encoding S.
      japonicum serpin (Sj serpin) was amplified from adult worm cDNA by using 5'-RACE
      PCR and subsequently cloned into the prokaryotic expression vector pET28c. The
      full-length Sj serpin fusion-protein with his-tag was expressed in E. coli,
      purified by affinity chromatography and used to immunize New Zealand white
      rabbits. Sj serpin is located on the tegument in S. japonicum adult worms.
      C57BL/6 mice immunized with Sj serpin induced the production of high levels of
      specific IgE and IgG1 subclass antibodies as well as a marked IL-4 response.
      Lymphocyte surface marker analysis revealed proliferation of CD19 expressing B
      cells, indicating a predominant Th2-type response to Sj serpin. Immunized mice
      developed moderate protection against infection of S. japonicum as demonstrated
      by a 36 and 39% reduction in the recovery of adult worms and eggs, respectively.
      These data suggested a role for Sj serpin as a vaccine candidate or as a novel
      target for anti-schistosome drugs.

PMID- 15946800
TI  - A seroepidemiologic survey of canine visceral leishmaniosis among apparently
      healthy dogs in Croatia.
AB  - Cross-sectional investigation was done on seroprevalence of Leishmania sp.
      infection among apparently healthy dogs in an area where canine leishmaniosis is
      endemic. Survey included 68 dogs living in the coastal city of Split, and 238
      dogs living in 12 villages scattered in the hinterland. Each dog was clinically
      examined for the presence of some discrete signs compatible with leishmaniosis
      and by dot-ELISA modification determined the presence of anti-Leishmania
      antibodies. The titre 1:600 and higher was regarded as positive in the study. The
      seroprevalence ranged from 0 to 42.85%, depending on the location. 54.34% of the
      seropositive dogs had moderately enlarged lymph nodes and/or some discrete
      changes on the skin. In our parasitological study, Leishmania sp. was isolated
      from several seropositive animals that had some clinical signs and from a few
      which did not have any. Data analysis revealed that serological positivity to
      Leishmania sp. was not associated with a dog's outdoor lifestyle and utility, but
      was associated with the gender and age.

PMID- 15946801
TI  - Effect of forage legumes and anthelmintic treatment on the performance,
      nutritional status and nematode parasites of grazing lambs.
AB  - Recent studies in New Zealand and the UK have shown that certain forages reduce
      parasitic infection in sheep. The aim of this experiment was to investigate the
      effects of legume forages compared to ryegrass on interactions between
      production, nutritional status and nematodes in grazing lambs. Twenty-four male
      lambs per forage treatment, half of which were treated with anthelmintics on Day
      0, grazed monocultures of lucerne (Medicago sativa), red clover (Trifolium
      pratense) and white clover (Trifolium repens) and were compared with lambs
      grazing perennial ryegrass (Lolium perenne). Individual faecal egg counts (FEC)
      and liveweight were determined every 7 days for 56 days, after which half the
      lambs were slaughtered to determine total nematode intensities (TNI). Results
      showed that lambs grazed on red or white clover, but not lucerne, had lower
      pooled mean FEC and improved liveweight performance compared to lambs grazing
      ryegrass. Lambs treated with anthelmintics had higher TNI compared to lambs not
      treated, due to a trend for more adult nematodes in lambs grazing lucerne and
      treated with anthelmintics than all other lambs, except those grazing red clover
      and also given anthelmintics. Lambs grazing white clover tended to have fewer
      adult nematodes than lambs grazing other forages. Examination of the nematode
      species showed a change in female T. circumcincta occurred in all lambs following
      anthelmintic treatment and that the forage species grazed by lambs affected
      individual parasite species. Lambs grazing white clover had fewer male and adult
      T. circumcincta compared to lambs grazing other forages, and lambs grazing
      lucerne had fewer adult T. circumcincta compared to lambs grazing ryegrass or red
      clover. Data on small intestine TNI showed that lambs grazing lucerne and given
      anthelmintics had more male adult nematodes than other lambs, except those
      grazing red clover and treated with anthelmintics. Results indicate that lucerne
      and red clover both increase the re-infection of grazing lambs with
      Trichostrongylus species compared to ryegrass following anthelmintic treatment.
      In conclusion, legume forages have the potential to contribute to the control of
      abomasal but not small intestine nematode parasites in finishing lamb systems.

PMID- 15946802
TI  - The pregnant mother with breast cancer: diagnostic and therapeutic management.
AB  - This review describes the epidemiology, pathology, clinical picture and
      therapeutic management of pregnant women with breast cancer. In addition, it
      covers other important issues like the safety of both diagnostic and treatment
      procedures, the indications for pregnancy termination, the mother and fetal
      outcome as well as the metastatic potential to the placenta and/or fetus. Several
      recommendations are also provided.

PMID- 15946803
TI  - Intranasal oxytocin administration attenuates the ACTH stress response in
      monkeys.
AB  - Social relationships protect against the development of stress-related
      psychiatric disorders, yet little is known about the neurobiology that regulates
      this phenomenon. Recent evidence suggests that oxytocin (OT), a neuropeptide
      involved in social bond formation, may play a role. This experiment investigated
      the effects of chronic intranasal OT administration on acute stress-induced
      hypothalamic-pituitary-adrenal (HPA) axis activation in adult female squirrel
      monkeys. Subjects were randomized to one of two experimental conditions. Monkeys
      were intranasally administered either 50 microg oxytocin (N = 6 monkeys) or 0
      microg oxytocin (N = 6 monkeys)/300 microl saline once a day for eight
      consecutive days. Immediately after drug administration on the eighth day, all
      monkeys were exposed to acute social isolation. Blood samples for determinations
      of adrenocorticotropic hormone (ACTH) and cortisol concentrations were collected
      after 30 and 90 min of stress exposure. Consistent with an anti-stress effect, OT
      treated monkeys exhibited lower ACTH concentrations compared to saline-treated
      monkeys after 90 min of social isolation (F(1,7) = 6.891; P = 0.034). No drug
      related differences in cortisol levels were observed, indicating that OT does not
      directly attenuate the adrenal stress response. Intranasal peptide administration
      has been shown to penetrate the central nervous system, and research must
      determine whether intranasally delivered OT exerts its effect(s) at a pituitary
      and/or brain level. This primate model offers critical opportunities to improve
      our understanding of the anti-stress effects of OT and may lead to novel
      pharmacological treatments for stress-related psychiatric disorders.

PMID- 15946804
TI  - Does paclitaxel decrease the interstitial fluid pressure and improve oxygenation
      in breast cancer in a schedule-dependent fashion?

PMID- 15946805
TI  - Sixteen-year changes and stable remission among treated and untreated individuals
      with alcohol use disorders.
AB  - AIMS: This study examined changes over a 16-year interval and predictors of
      stable remission among previously untreated individuals with alcohol-use
      disorders who did not obtain help or who entered either alcoholics anonymous (AA)
      or professional treatment in the first year after initially seeking help. DESIGN
      AND MEASURES: A sample of individuals (N = 461) who initiated help-seeking was
      surveyed at baseline and 1, 3, 8, and 16 years later. In addition to providing
      information on life history of drinking at each contact point, participants
      described their current alcohol-related and psychosocial functioning and life
      context, and coping responses. FINDINGS: Irrespective of whether or not
      individuals obtained help, their alcohol-related functioning, life context, and
      coping improved. However, individuals who obtained help (AA or treatment) in the
      first year improved more and were more likely to achieve stable remission than
      those who did not. Nevertheless, the factors associated with stable remission
      were comparable for individuals who did and those who did not obtain timely help.
      CONCLUSIONS: Compared with individuals who do not obtain timely help, those who
      enter either AA or treatment relatively soon after initiating help-seeking
      improve more quickly and achieve higher long-term remission rates.

PMID- 15946806
TI  - HP0958 is an essential motility gene in Helicobacter pylori.
AB  - Motility is an essential colonization factor for the human gastric pathogen
      Helicobacter pylori. The H. pylori genome encodes most known flagellar proteins,
      although a number of key transcription regulators, chaperones, and structural
      proteins have not yet been identified. Using recently published yeast two-hybrid
      data we identified HP0958 as a potential motility-associated protein due to its
      strong interactions with RpoN (sigma(54)) and FliH, a flagellar ATPase regulator.
      HP0958 exhibits no sequence similarity to any published flagellar genes but
      contains a carboxy-terminal zinc finger domain that could function in nucleic
      acid or protein binding. We created a HP0958 mutant by inserting a
      chloramphenicol resistance marker into the gene using a PCR-based allelic
      exchange method and the resultant mutant was non-motile as measured by a
      BacTracker instrument. Electron microscopic analysis revealed that the HP0958
      mutant cells were aflagellate and Western blot analysis revealed a dramatic
      reduction in flagellin and hook protein production. The HP0958 mutant also showed
      decreased transcription of flgE, flaB and flaA as well as the checkpoint genes
      flhA and flhF. Expression of flgM was increased relative to the wild-type and
      both rpoN and fliA (sigma(28)) expression were unchanged. We conclude that HP0958
      is essential for normal motility and flagella production, and represents a novel
      flagellar component in the epsilon proteobacteria.

PMID- 15946807
TI  - Characterization and functional significance of myotrophin: a gene with multiple
      transcripts.
AB  - The underlying mechanism for the development of cardiac hypertrophy that advances
      to heart failure is not known. Many factors have been implied to play a role in
      this process. Among others, we have isolated and identified myotrophin, a factor
      that stimulates myocytes growth, from spontaneously hypertensive rat (SHR) heart
      and patients with dilated cardiomyopathy. The gene encoding myotrophin has been
      cloned and expressed in E. coli. Recently, myotrophin gene has been mapped and
      shown to be a novel gene localized in human chromosome 7q-33. To define the
      characteristics of each transcript and its pathophysiological significance, we
      examined transcripts of myotrophin in SHR heart during progression of
      hypertrophy. Northern blot analysis of myotrophin mRNA showed multiple
      transcripts. We isolated and characterized various myotrophin cDNA clones
      corresponding to the multiple transcripts by 5' "stretch plus" rat heart cDNA
      library screening. Sequence analysis of these cDNA clones indicates that each
      clone has a unique 5' UTR and multiple 3' UTR with varying lengths, repeated
      ATTTA motifs and many polyadenylation signals. In vitro transcripts generated
      from all these myotrophin-specific cDNA clones translate in vitro to a 12-kD
      protein. Among pathophysiological significance, we determined mRNA expression in
      9 days old, 3 weeks old and 31 weeks old and observed a linear increased during
      the progression of hypertrophy. In WKY, this mRNA level remained the same
      throughout the growth and development of hypertrophy. Our data strongly suggest
      that myotrophin appears to be a candidate gene for cardiac hypertrophy and heart
      failure.

PMID- 15946808
TI  - Transfer of antivirals across the human placenta.
AB  - BACKGROUND: Viruses cross the placenta and infect the fetus. Antivirals are
      administered to pregnant women to protect them and the fetus against the viruses.
      It is necessary to know which antivirals cross the placenta and reach the fetal
      circulation in pharmacologically significant concentrations in order to plan
      antiviral therapy. AIMS: This article reviews the literature on the placental
      transfer of antivirals against HIV. The review considers also the placental
      transfer of acyclovir and ganciclovir, which are used against the herpes simplex
      virus and the cytomegalovirus, respectively. STUDY DESIGN: Firstly, a medline was
      performed with the following key words "placental transfer of antivirals".
      Secondly, a medline was performed with the key words "placenta transfer of..."
      followed by the name of a single antiviral and it was repeated for 20 antivirals.
      Thirdly, another medline was performed using the following key words
      "pharmacokinetics of antiviral in newborn" in order to collect those articles
      which describe in vivo transfer of antivirals. The literature was critically read
      and a written note was produced. RESULTS: The literature on the placental
      transfer of antivirals includes studies in vitro perfusing the human placenta and
      studies performed in vivo in which the cord and maternal antiviral plasma
      concentrations are compared. Both the results obtained in vitro and in vivo show
      that the protease inhibitors poorly transfer the placenta because of their great
      molecular weight. With the exception of didanosine, the nucleoside reverse
      transcriptase inhibitors and nelfinavir, a non-nucleoside reverse transcriptase
      inhibitor, cross the placenta and the cord, and maternal plasma concentrations
      equilibrate. CONCLUSIONS: In vitro and in vivo results are consistent with the
      view that the nucleoside reverse transcriptase inhibitors cross the human
      placenta and produce significant pharmacological concentrations in the fetal
      circulation. Nevirapine, the only studied non-nucleoside reverse transcriptase
      inhibitor, reach the equilibrium between the fetal and maternal concentration,
      whereas the protease inhibitors have a poor transfer across the human placenta.

PMID- 15946809
TI  - A comparison of BoviPure and Percoll on bull sperm separation protocols for IVF.
AB  - In the present study, we have examined the effect of density gradient
      preparations BoviPure and Percoll on bull sperm separation and the in vitro
      fertilization (IVF) and culture (IVC) results. Frozen/thawed semen from five
      simmental bulls were pooled. Sperm quality parameters such as sperm motility,
      concentration, membrane activity (HOS assay), membrane integrity (SYBR-14/PI
      assay) and acrosomal status (EthD-1/FITC-PSA assay) were evaluated before and
      after sperm processing for IVF using BoviPure and Percoll density gradient
      separations. The results of the evaluated parameters before sperm processing
      were: motility 50%, concentration 82.33x10(6)spz/mL, membrane activity 39.05%,
      membrane integrity 42.97% and the acrosomal status 46.90% of the live spermatozoa
      with intact acrosomes. After sperm processing with BoviPure and Percoll the
      motility was 66.67 and 64.17%, the concentration was 25.50x10(6) and
      27.67x10(6)spz/mL, the membrane activity was 53.78 and 56.58%, the membrane
      integrity was 70.85 and 68.76% of and the acrosomal status was 74.16 and 67.46%
      of the live spermatozoa with intact acrosomes, respectively. Percentages were
      referred to the total number of spermatozoa. There were significant differences
      (P<0.05) between the evaluated parameters before and after sperm processing for
      both separation protocols. We found no significant differences (P>0.05) regarding
      sperm evaluation parameters between the protocols. A total of 492 oocytes were
      matured and fertilized in vitro and cultured in SOFaaBSA in six replicates. The
      cleavage (D2) and blastocysts (D7) rate were significantly higher (P<0.05) for
      the BoviPure group compared to the Percoll group: 75.80 and 28.21%; 61.58 and
      20.83%, respectively. However, the number of hatched blastocysts (D10) did not
      differ significantly between sperm separation protocols (P>0.05). Our results
      indicate that both protocols gave suitable sperm for IVF. This finding and the
      similarity between those two density gradient preparations suggests that BoviPure
      is a good alternative for sperm separation in bovine IVF.

PMID- 15946810
TI  - Ultra-deformable liposomes containing bleomycin: in vitro stability and toxicity
      on human cutaneous keratinocyte cell lines.
AB  - Formulations of ultra-deformable liposomes containing bleomycin (Bleosome) have
      previously been described and proposed for topical treatment of skin cancer [Lau,
      K.G., Chopra, S., Maitani, Y., 2003. Entrapment of bleomycin in ultra-deformable
      liposomes. S. T. P. Pharm. Sci. 13, 237-239]. In this study, the stability of
      various Bleosome formulations was characterised and a purification process was
      established to isolate Bleosome for testing on cultures of either human cutaneous
      keratinocytes (NEB-1) immortalised by human papilloma virus (HPV)-type 16, or a
      spontaneously immortalised human squamous cell carcinoma (SCC) from a primary
      tumour. Bleosome facilitated entrapment of high concentrations of active
      bleomycin and samples purified by gel-filtration chromatography remained stable
      during 7 days of storage at 4 degrees C or at room temperature. Serially-diluted
      samples of this purified, high-strength product, 'high dose' were applied onto
      keratinocyte cell cultures to elucidate Bleosome LD50 profiles. In vitro data
      revealed that the LD50 of bleomycin encapsulated in Bleosome was approximately
      three-fold higher than free bleomycin solution for SCC cells, and nearly 30 times
      higher for NEB-1 cells. However, Bleosome containing 30 microg/ml of active
      bleomycin killed more than twice as many SCC cells than NEB-1 cells. At that
      concentration, the potency of liposomal bleomycin on causing cell death of SCC
      cells was found to be similar to that of free bleomycin solution. This effect was
      not seen on NEB-1 cells. It seems that SCC cells were particularly susceptible to
      Bleosome containing high levels of bleomycin. Results from these experiments
      promote the development of a novel product for the topical treatment of skin
      cancer.

PMID- 15946811
TI  - Micelle-like nanoparticles of PLA-PEG-PLA triblock copolymer as chemotherapeutic
      carrier.
AB  - Triblock copolymer PLA-PEG-PLA were synthesized using ring opening polymerization
      with different LA/EG ratio. Micellar aggregates were prepared from these block
      copolymers and characterized. The degradation characteristics of selected
      copolymers were assessed in both micellar and film forms. Surface segregation of
      PEG was also quantified as a function of copolymer composition. Anti-cancer drugs
      5-FU and paclitaxel were loaded into the micellar nanospheres with good
      efficiency. The drug release profile showed good control over the release of
      paclitaxel from these polymers.

PMID- 15946812
TI  - Protective role of Melissa officinalis L. extract on liver of hyperlipidemic
      rats: a morphological and biochemical study.
AB  - In this study, the effects of Melissa officinalis L. extract on hyperlipidemic
      rats were investigated, morphologically and biochemically. The animals were fed a
      lipogenic diet consisting of 2% cholesterol, 20% sunflower oil and 0.5% cholic
      acid added to normal chow and were given 3% ethanol for 42 days. The plant
      extract was given by gavage technique to rats to a dose of 2 g/kg every day for
      28, 14 days after experimental animals done hyperlipidemia. The degenerative
      changes were observed in hyperlipidemic rats, light and electron microscopically.
      There was a significant increase in the levels of serum cholesterol, total lipid,
      alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase
      (ALP), a significant decrease in the levels of liver tissue glutathione (GSH), a
      significant increase in the levels of tissue lipid peroxidation (LPO) in this
      group. On the other hand, the administration of Melissa officinalis L. extract
      reduced total cholesterol, total lipid, ALT, AST and ALP levels in serum, and LPO
      levels in liver tissue, moreover increased glutathione levels in the tissue. As a
      result, it was suggested that Melissa officinalis L. extract exerted an
      hypolipidemic effect and showed a protective effect on the liver of
      hyperlipidemic rats.

PMID- 15946813
TI  - Royal jelly has estrogenic effects in vitro and in vivo.
AB  - Royal jelly (RJ) from honeybees (Apis mellifera) is traditionally thought to
      improve menopausal symptoms. The potential estrogenic activities of RJ were
      investigated using various approaches. RJ competed for binding of 17beta
      estradiol to the human estrogen receptor alpha and beta but its affinities were
      weak compared with diethylstilbestrol and phytoestrogens. The reporter gene
      expression assays suggested that 0.1-1 mg/ml RJ activated estrogen receptors,
      leading to enhanced transcription of a reporter gene through an estrogen
      responsive element. 1 mg/ml RJ stimulated the mRNA expression of estrogen
      responsive pS2 and vascular endothelial growth factor (VEGF) by increasing gene
      transcription in MCF-7 cells. Treatment with RJ at concentrations ranging from
      0.5 to 1 mg/ml enhanced MCF-7 cell proliferation, but concomitant treatment with
      1 microM tamoxifen blocked this effect. In vivo studies using ovariectomized rats
      showed that 17beta-estradiol (20 mg/kg, s.c.) treatment restored VEGF expression
      in both uterus and brain, whereas RJ (1 g/kg, s.c.) restored it in uterus but not
      in brain. These findings provide evidence that RJ has estrogenic activities
      through interaction with estrogen receptors followed by endogenous gene
      expressions.

PMID- 15946814
TI  - Distribution of ethyl glucuronide in rib bone marrow, other tissues and body
      liquids as proof of alcohol consumption before death.
AB  - Postmortem ethyl glucuronide (EtG) concentrations in rib bone marrow, liver,
      muscle, fat tissue, urine, blood and bile have been determined by LC-MS/MS.
      Samples have been taken from twelve corpses during autopsies. In nine corpses EtG
      could be detected, corresponding blood ethanol concentrations (BAC) were 0.04
      0.37 g%. In three cases, no EtG was found; two of these cases showed postmortem
      BACs - possibly due to putrefaction - of 0.01 and 0.1g%. In rib bone marrow,
      which is easily accessible during autopsy, EtG concentrations (0.77-9.36
      microg/g) have been lower than in blood (2.24-20.46 microg/mL) in eight of nine
      cases and comparable or higher than in muscle tissue. Therefore, rib bone marrow
      has been found suitable as matrix for EtG determination. The highest EtG
      concentrations have been found in urine in all but one case, where the resorption
      of ethanol had been incomplete. Second highest EtG concentrations have been
      detected in liver samples. In two cases with putrefaction, EtG could not be
      detected. In these cases, the detectable ethanol might have been produced
      partially or in total by postmortem fermentation. However, instability of EtG
      during putrefaction cannot be totally excluded which might result in a total loss
      of EtG.

PMID- 15946815
TI  - Allele frequencies of 15 STR loci of Luoba ethnic group in Tibet (Southwestern
      China).
AB  - Allele frequency data for 15 short tandem repeat (STR) loci included in the
      AmpFlSTR Identifiler kit were obtained from a sample of 93 healthy unrelated
      individuals of Luoba population born in Tibet Autonomy Region of China
      (Southwestern China). In these samples, 141 alleles and 365 genotypes were
      observed for 15 STR loci. The distribution of these observed genotypes were not
      significantly different from the expected distribution according to Hardy
      Weinberg equilibrium.

PMID- 15946816
TI  - Simultaneous quantification of different cyclodextrins and Gantrez by HPLC with
      evaporative light scattering detection.
AB  - A rapid and simple HPLC method with evaporative scattering detection (ELSD) has
      been developed for the separation and quantitation of beta-cyclodextrin (beta
      CD), 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) and poly(methyl vinyl ether
      co-maleic anhydride) (Gantrez). Separation was carried out on a Zorbax Eclipse
      XDB-Phenyl narrow bore column, with water-acetonitrile in gradient elution as
      mobile phase at a flow-rate of 0.25 ml/min. Polyethylenglycol 6000 was used as
      internal standard. The limit of quantification was of about 0.2 mg/ml for
      cyclodextrins and 0.05 mg/ml for Gantrez. The precision did not exceed 7%. This
      method was successfully applied to the rapid analysis of CD-Gantrez nanoparticle
      conjugates without interference from other components of the formulation.

PMID- 15946817
TI  - A high performance liquid chromatography method for the simultaneous
      determination of arctiin, chlorogenic acid and glycyrrhizin in a Chinese
      proprietary medicine.
AB  - A high performance liquid chromatography (HPLC) method was developed for the
      simultaneous determination of arctiin, chlorogenic acid and glycyrrhizin in the
      tablets of a Chinese proprietary medicine named, "Yin Qiao Jie Du Pian". The
      analysis was performed by a reverse phase gradient elution, using an aqueous
      mobile phase (containing 0.4% acetic acid and 4.5% tetrahydrofuran) modified by
      acetonitrile and detection made simultaneously at three wavelengths. The method
      was validated for specificity, accuracy, precision and limits of detection and
      quantification. Tablets of seven commercial brands were analyzed and found to
      contain different amounts of the three bioactive markers. This raised the
      question of the quality and the efficacy of the products. The method developed
      can be used for the quality control of "Yin Qiao Jie Du" tablets.

PMID- 15946818
TI  - Identification and quantitation of eleven sesquiterpenes in three species of
      Curcuma rhizomes by pressurized liquid extraction and gas chromatography-mass
      spectrometry.
AB  - In this paper, GC-MS and pressurized liquid extraction (PLE) was developed for
      identification and quantitative determination/estimation 11 sesquiterpenes
      including germacrene D, curzerene, gamma-elemene, furanodienone, curcumol,
      isocurcumenol, furanodiene, germacrone, curdione, curcumenol and neocurdione in
      Ezhu which are derived from three species of Curcuma, i.e., Curcuma phaeocaulis,
      Curcuma wenyujin and Curcuma kwangsiensis by using an analogue as standard. The
      results showed the methodology could quantitatively compare the quality of three
      species of Curcuma. The contents of investigated sesquiterpenes in three species
      of Curcuma were high variant. Hierarchical clustering analysis based on
      characteristics of 11 identified peaks in GC profiles showed that 18 samples were
      divided into two main clusters, C. phaeocaulis and C. wenyujin, respectively. C.
      kwangsiensis showed the characters closed to C. phaeocaulis or C. wenyujin based
      on its location. Five components such as furanodienone, germacrone, curdione,
      curcumenol and neocurdione were optimized as markers for quality control of Ezhu.

PMID- 15946819
TI  - Classification of drugs in absorption classes using the classification and
      regression trees (CART) methodology.
AB  - Classification and regression trees (CART) were evaluated for their potential use
      in a quantitative structure-activity relationship (QSAR) context. Models were
      build using the published absorption values for 141 drug-like molecules as
      response variable and over 1400 molecular descriptors as potential explanatory
      variables. Both the role of two- and three-dimensional descriptors and their
      relative importance were evaluated. For the used dataset, CART models showed high
      descriptive and predictive abilities. The predictive abilities were evaluated
      based on both cross-validation and an external test set. Application of the
      variable ranking method to the models showed high importances for the n
      octanol/water partition coefficient (logP) and polar surface area (PSA). This
      shows that CART is capable of selecting the most important descriptors, as known
      from the literature, for the absorption process in the intestinal tract.

PMID- 15946820
TI  - The effect of recombinant human osteogenic protein-1 on growth plate repair in a
      sheep model.
AB  - Injuries to the growth plate in children can result in bone bridge formation,
      which ultimately lead to limb length and angular deformities. The histological
      and molecular changes associated with growth plate repair following the
      Langenskiold procedure, a surgical technique used to remove impeding bone
      bridges, in conjunction with administration of recombinant human osteogenic
      protein-1 (rhOP-1) were examined using a sheep model. Following treatment with
      rhOP-1 there was an increase in the height of the growth plate immediately
      adjacent to the defect compared to untreated animals. The expression of type I
      collagen, osteopontin and decorin were observed in the growth plate adjacent to
      the defect in the untreated animals at day 56, but this response was accelerated
      in the rhOP-1 treated animals, with these molecules seen as early as day 7.
      Therefore, treatment with rhOP-1 initiated a complex response that was both
      chondrogenic and osteogenic in nature.

PMID- 15946821
TI  - Restoration of bone defect and enhancement of bone ingrowth using partially
      demineralized bone matrix and marrow stromal cells.
AB  - PURPOSE: This study aimed to investigate the capability of combining marrow
      stromal cells (MSC) and partially demineralized bone matrix (PDBM) to fill bone
      defect and enhance bone ingrowth using a canine non-weight-bearing gap model.
      METHODS: Custom-made implants with 3mm gap between the porous surface and the
      host bone were used. The implants were inserted into the distal femurs of 25
      mongrel dogs and the gaps were randomly assigned to be filled with culture
      expanded autologous MSC-loaded PDBM, autograft, fresh-frozen allograft, PDBM
      alone, or nothing as controls. Histomorphometry using backscattered scanning
      electron microscopic examination, and mechanical push-out test were performed at
      6 months after surgery. RESULTS: Histomorphometry showed that amounts of bone
      regeneration in the gap and bone ingrowth into the porous-coated surface in the
      MSC-loaded PDBM-treated group were comparable to those of autograft-treated group
      and were significantly greater than those of allograft-treated, PDBM-treated, or
      non-grafted groups. Mechanical test showed the same differences. CONCLUSION: The
      results of this study showed that combining PDBM and autologous culture-expanded
      MSC restored bone stock and enhanced bone ingrowth into the porous-coated area in
      a canine non-weight-bearing gap model. This combination may provide an option for
      reconstructing bone defect when we perform a cementless revision arthroplasty.

PMID- 15946822
TI  - Spatial and temporal localization during embryonic and fetal human development of
      the transcription factor SIM2 in brain regions altered in Down syndrome.
AB  - Human SIM2 is the ortholog of Drosophila single-minded (sim), a master regulator
      of neurogenesis and transcriptional factor controlling midline cell fate
      determination. We previously localized SIM2 in a chromosome 21 critical region
      for Down syndrome (DS). Here, we studied SIM2 gene using a new approach to
      provide insights in understanding of its potential role in human development. For
      the first time, we showed SIM2 spatial and temporal expression pattern during
      human central nervous system (CNS) development, from embryonic to fetal stages.
      Additional investigations were performed using a new optic microscopy technology
      to compare signal intensity and cell density [M. Rachidi, C. Lopes, S. Gassanova,
      P.M. Sinet, M. Vekemans, T. Attie, A.L. Delezoide, J.M. Delabar, Regional and
      cellular specificity of the expression of TPRD, the tetratricopeptide Down
      syndrome gene, during human embryonic development, Mech. Dev. 93 (2000) 189-
      193]. In embryonic stages, SIM2 was identified predominantly in restricted
      regions of CNS, in ventral part of D1/D2 diencephalic neuroepithelium, along the
      neural tube and in a few cell subsets of dorsal root ganglia. In fetal stages,
      SIM2 showed differential expression in pyramidal and granular cell layers of
      hippocampal formation, in cortical cells and in cerebellar external granular and
      Purkinje cell layers. SIM2 expression in embryonic and fetal brain could suggest
      a potential role in human CNS development, in agreement with Drosophila and mouse
      Sim mutant phenotypes and with the conservation of the Sim function in CNS
      development from Drosophila to Human. SIM2 expression in human fetal brain
      regions, which correspond to key structures for cognitive processes, correlates
      well with the behavioral phenotypes of Drosophila Sim mutants and transgenic mice
      overexpressing Sim2. In addition, SIM2-expressing brain regions correspond to the
      altered structures in DS patients. All together, these findings suggest a
      potential role of SIM2 in CNS development and indicate that SIM2 overexpression
      could participate to the pathogenesis of mental retardation in Down syndrome
      patients.

PMID- 15946823
TI  - Quality control in breast cancer surgery.
AB  - Quality assurance is the process by which quality care can be assessed. The
      general principles include setting a standard with the aim of achieving
      particular outcomes, followed by the evaluation of parameters that allow for
      quality assessment. Locoregional and survival outcomes are the major parameters
      but require years to evaluate and have other limitations. Other parameters
      therefore may assist in evaluation, such as the availability of the structures
      and processes required to achieve desired outcomes. Unlike chemotherapy and
      radiotherapy the quality of surgery is difficult to quantify, yet it is central
      to the issue of locoregional control and survival. In breast cancer surgery,
      quality control starts at the diagnostic service; from referral by the family
      practitioner to the appropriate triage of patients thereby preventing diagnostic
      delays. The surgical oncologist is pivotal in the multidisciplinary input
      necessary with both radiologists and pathologists in achieving the correct
      preoperative diagnoses of symptomatic and screen detected lesions as specified by
      many of the guidelines. Quality control of the operative surgery addresses issues
      such as training, volume and life audit of the surgeon. Standardisation of
      operative technique, pathology reporting with emphasis on specimen orientation
      and margins, management of the axilla and how it impacts on adjuvant treatment
      are other important issues. More recently, the availability of breast
      reconstruction services and the development of the oncoplastic surgeon is
      becoming an important quality issue. Finally, the quality of the follow up
      process provides the tools to assess the outcome of both the patient and the
      service.

PMID- 15946824
TI  - ASR for emotional speech: clarifying the issues and enhancing performance.
AB  - There are multiple reasons to expect that recognising the verbal content of
      emotional speech will be a difficult problem, and recognition rates reported in
      the literature are in fact low. Including information about prosody improves
      recognition rate for emotions simulated by actors, but its relevance to the freer
      patterns of spontaneous speech is unproven. This paper shows that recognition
      rate for spontaneous emotionally coloured speech can be improved by using a
      language model based on increased representation of emotional utterances. The
      models are derived by adapting an already existing corpus, the British National
      Corpus (BNC). An emotional lexicon is used to identify emotionally coloured
      words, and sentences containing these words are recombined with the BNC to form a
      corpus with a raised proportion of emotional material. Using a language model
      based on that technique improves recognition rate by about 20%.

PMID- 15946825
TI  - Characterization of olfactory bulb glomeruli in schizophrenia.
AB  - Olfactory deficits, observed in schizophrenia, may be associated with a
      disruption of synaptic transmission in the olfactory system. Using
      immunohistochemistry and optical densitometry, we assessed the integrity of the
      synaptic connection between olfactory receptor neurons and olfactory bulb target
      neurons in schizophrenia by comparing the level of eight proteins, expressed in
      the olfactory bulb glomeruli, among schizophrenia and control subjects. In
      schizophrenia, no change was observed in the levels of OMP, GAP43 and NCAM,
      proteins expressed by olfactory receptor neurons, suggesting an intact
      innervation of the olfactory bulb by these neurons. This was supported by the
      absence of change in calbindin level, which has been shown to decrease after the
      destruction of the olfactory epithelium. The level of synaptophysin, a pre
      synaptic protein, was also unchanged. These findings suggested that axons of
      olfactory receptor neurons establish synapses with their olfactory bulb targets
      in schizophrenia. The absence of change in the level of poorly phosphorylated
      neurofilament of moderate and high molecular weight (NFM/HP) suggested no lack of
      dendritic innervation despite a previously seen reduction of glomerular MAP2
      level in schizophrenia subjects. This and above findings were consistent with the
      absence of change in the level of beta-tubulin III, a protein expressed by
      neurons of both olfactory epithelium and bulb. Finally, we noted no significant
      decrease in trkB level, a neurotrophin receptor involved in the olfactory
      epithelium maintenance. This study showed no evidence of major structural
      alteration of the synapse between the olfactory epithelium and bulb in
      schizophrenia.

PMID- 15946826
TI  - Tellurite effects on Rhodobacter capsulatus cell viability and superoxide
      dismutase activity under oxidative stress conditions.
AB  - Cells of the facultative photosynthetic bacterium Rhodobacter capsulatus (MT1131
      strain) incubated with 10 microg ml-1 of the toxic oxyanion tellurite (TeO2-(3))
      exhibited an increase in superoxide dismutase activity. The latter effect was
      also seen upon incubation with sublethal amounts of paraquat, a cytosolic
      generator of superoxide anions (O2-), in parallel with a strong increase in
      tellurite resistance (TeR). A mutant strain (CW10) deficient in SenC, a protein
      with similarities to peroxiredoxin/thiol:disulfide oxidoreductases and a
      homologue of mitochondrial Sco proteins, was constructed by interposon
      mutagenesis via the gene transfer agent system. Notably, the absence of SenC
      affected R. capsulatus resistance to periplasmic O2- generated by
      xanthine/xanthine oxidase but not to cytosolic O2- produced by paraquat. Further,
      the absence of SenC did not affect R. capsulatus tellurite resistance. We
      conclude that: (1) cytosolic-generated O2- enhances TeR of this bacterial
      species; (2) small amounts of tellurite increase SOD activity so as to mimic the
      early cell response to oxidative stress; (3) SenC protein is required in
      protection of R. capsulatus against periplasmic oxidative stress; and finally,
      (4) SenC protein is not involved in TeR, possibly because tellurite does not
      generate O-2 at the periplasmic space level.

PMID- 15946827
TI  - Direct quantification of protein partitioning in oil-in-water emulsion by front
      face fluorescence: avoiding the need for centrifugation.
AB  - The quantification of proteins adsorbed at the oil-in-water interface is often
      difficult since it requires separation of fat globules from the aqueous phase
      that may damage the fat globule size and/or modify the interfacial composition.
      Front-face fluorescence spectroscopy was used to characterize the protein
      partitioning between the aqueous and oil phases of emulsions without separating
      these two phases. Different emulsions based on skim milk powder (SMP), two mono-
      and di-glyceride (MDG) mixtures (saturated and partially unsaturated), and three
      fats (hydrogenated and refined coconut oils and refined palm oil) were studied.
      The impact of an ageing period (24 h at 4 degrees C) was also investigated to
      typify the first step of ice cream processing. The emulsions were characterized
      for protein partitioning, immediately following emulsification and after ageing,
      using the Bradford spectrophotometric method, applied to the aqueous phase
      recovered after emulsion centrifugation. In parallel, the emulsions were
      characterized by their tryptophan emission fluorescence spectra. The area of the
      peaks at 333 nm, of the fourth-derivative fluorescence spectra corresponding to
      the amount of proteins present in the aqueous phase of emulsions, was well
      correlated with the Bradford measurements (r2=0.91). This amount was also
      calculated from the fluorescence calibration curve obtained with SMP in solution.
      In conclusion, front-face fluorescence spectroscopy appeared to be a powerful and
      simple technique allowing the quantification of different populations of protein
      in an emulsified system, i.e., in the aqueous phase and loaded at the fat globule
      interface.

PMID- 15946828
TI  - Transport of nanoparticles across an in vitro model of the human intestinal
      follicle associated epithelium.
AB  - An in vitro model of the human follicle associated epithelium (FAE) was
      characterized and the influence of nanoparticle properties on the transcellular
      transport across the in vitro model was investigated. The model was established
      by co-culturing Caco-2 and Raji cells, with Caco-2 cells alone as control. The
      conversion of Caco-2 cells to follicle associated epithelium (FAE) like cells was
      monitored by following the surface expression of beta1-integrins
      (immunofluorescence) and nanoparticle transport (flow cytometry). The influence
      of the nanoparticle concentration at the apical side, temperature, size and
      surface properties of nanoparticles on transport was evaluated, as well as the
      influence of transport conditions. The conversion of Caco-2 cells into FAE-like
      cells occurred. The transport was concentration, temperature and size-dependent.
      Aminated nanoparticles were more efficiently transported than carboxylated
      nanoparticles, suggesting a role of nanoparticle surface functional groups and
      hydrophobicity, possibly leading to a different pattern of protein adsorption at
      their surface. In conclusion, this in vitro model is a promising tool to study
      the role of M cells in transintestinal nanoparticle transport, as well as to
      evaluate new drug delivery systems.

PMID- 15946829
TI  - [Anthropometry measurement of term newborns at Ouagadougou (Burkina Faso)].

PMID- 15946830
TI  - [Taking charge of newborns in Sub-Saharan Africa's maternity care: a challenge
      for the millennium].

PMID- 15946831
TI  - [Longitudinal changes in body composition and basal metabolic rate in
      institutionalized or domiciled obese adolescents].
AB  - The prevalence of obesity in children has increased dramatically during the past
      decades, and requires efficient care. OBJECTIVES: To determine changes in
      anthropometric parameters and basal metabolic rate (BMR) in obese adolescents
      during and after 2 types of weight-reduction programs. SUBJECTS AND METHODS:
      Twenty-six adolescents (group I, Z-score of BMI = 4.72) followed a 9-month-weight
      reduction program including a moderate energy restriction and regular physical
      activities in a specialized institution. In addition, 39 adolescents (group E, Z
      score of BMI = 2.83) followed at home a 9-month-weight reduction program
      including medical and dietetic advices. Body composition (by impedancemetry) and
      BMR (by indirect calorimetry) were assessed before the beginning (M0), 4 months
      after (M4) and at the end (M9) of the programs, then 4 months (M13) and 16 month
      (M25) after the end of the weight-reduction programs. RESULTS: Twenty-two
      adolescents in group I and 20 adolescents in group E completed the study. At M0,
      age, body weight (BW), fat-free mass (FFM) and BMR of subjects of group I were
      higher (1.0 year, 36 %, 30 % and 23 %, respectively, P < 0.001), than those of
      group E. Pubertal stage and percentage of fat mass (FM) were not significantly
      different between the 2 groups. At M9, adolescents of group I showed significant
      reductions in BW and FM (-19 and -37 %, respectively, P < 0.001), but not
      significant differences in FFM. In addition, BMR decreased significantly between
      M0 and M4, both in absolute value (-6.7%, P < 0.001) and after adjustment for FFM
      (-5.8%, P < 0.001), and the difference was maintained until M9. Between M9 and
      M13, BW and Z-score of BMI were maintained in 12 adolescents, but increased
      (+9.7% and 14.8%, respectively, P < 0.001) in 10 adolescents. However, BMR did
      not change significantly in all adolescents. Between M13 and M25, BW, FM, FFM and
      BMR increased significantly (+13%, +34%, +6% et +5%, respectively, P < 0.001).
      During the 25 month period, adolescents of group E showed significant increases
      in BW, FFM and BMR (+8%, +14% and +10%, respectively, P < 0.001), and maintained
      their Z-score and FM. CONCLUSION: The reduction in BMR during the weight
      reduction program at the institution could contribute to body weight regain in
      the post-obese adolescents if they do not maintain the lifestyle habits taught
      during the weight-reduction period. In other respects, Z-score was stabilized in
      51% of domiciled obese adolescents.

PMID- 15946832
TI  - Adipose tissue and the immune system.
AB  - Adipocytes anatomically associated with lymph nodes (and omental milky spots)
      have many special properties including fatty acid composition and the control of
      lipolysis that equip them to interact locally with lymphoid cells. Lymph node
      lymphocytes and tissue dendritic cells acquire their fatty acids from the
      contiguous adipocytes. Lymph node-derived dendritic cells suppress lipolysis in
      perinodal adipocytes but those that permeate the adipose tissue stimulate
      lipolysis, especially after minor, local immune stimulation. Inflammation alters
      the composition of fatty acids incorporated into dendritic cells, and that of
      node-containing adipose tissue, counteracting the effects of dietary lipids. Thus
      these specialised adipocytes partially emancipate the immune system from
      fluctuations in the abundance and composition of dietary lipids. Prolonged, low
      level immune stimulation induces the local formation of more adipocytes,
      especially adjacent to the inflamed lymph node. This mechanism may contribute to
      hypertrophy of the mesentery and omentum in chronic inflammatory diseases such as
      HIV-infection, and in smokers. Paracrine interactions between adipose and
      lymphoid tissues are enhanced by diets rich in n-6 fatty acids and attentuated by
      fish oils. The latter improve immune function and body conformation in animals
      and people. The partitioning of adipose tissue in many depots, some specialised
      for local, paracrine interactions with other tissues, is a fundamental feature of
      mammals.

PMID- 15946833
TI  - Pattern of diffusion disturbance related to clinical diagnosis: The K(CO) has no
      diagnostic value next to the DL(CO).
AB  - AIM OF THE STUDY: The diffusion capacity of the lung for carbon monoxide (DL(CO))
      is an important tool in the diagnosis and follow-up of patients with pulmonary
      diseases. In case of a decreased DL(CO) the K(CO), defined as DL(CO)/V(A) (V(A)
      is alveolar volume), can differentiate between normal alveolocapillary membrane
      (normal K(CO)) and abnormal alveolocapillary membrane (low K(CO)). The latter
      category consists of decreased surface of the membrane, increased thickness or
      decreased perfusion of ventilated alveoli. The V(A)/TLC (TLC is total lung
      capacity determined by whole body plethysmography) can partially differentiate
      between these categories. The aim of this study was to investigate the diagnostic
      value of the specific diffusion disturbances, which can be constructed by
      combining the DL(CO), K(CO) and V(A)/TLC. METHODS: In 460 patients the diagnosis
      made by clinicians were fitted into five diagnostic categories: asthma, chronic
      obstructive pulmonary disease (COPD), treatment effects of haematologic
      malignancies, heart failure and diffuse parenchymal lung diseases (DPLD). These
      categories were linked to the pattern of diffusion disturbance. RESULTS: Almost
      all patients with asthma have a normal DL(CO), most patients in the other groups
      do not have the expected pattern of diffusion disturbance, especially in the
      group with DPLD a bad match is observed. CONCLUSION: In this study the pattern of
      diffusion disturbance is of limited use in establishing a diagnosis. The use of
      the K(CO) next to the DL(CO) has no additional diagnostic value. Regional
      ventilation-perfusion inequality probably forms an important underlying mechanism
      of decreased DL(CO).

PMID- 15946834
TI  - The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8
      levels in stable COPD patients.
AB  - Chronic obstructive pulmonary disease (COPD) is characterised by a chronic
      inflammatory process in the large and small airways, as well as in the lung
      parenchyma. Although the role of oral corticosteroids in the management of acute
      exacerbations of COPD is well documented, its role in stable COPD is not clear.
      We examined the anti-inflammatory effect of inhaled budesonide on the percentage
      of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL)
      and their correlation with spirometry and symptom scores. Twenty-six patients
      with stable COPD were randomised, in a double-blinded, placebo-controlled trial
      with either 800 microg of inhaled budesonide or placebo for a 6-month period. The
      budesonide-treated subjects had significant reductions in IL-8 levels in the BAL
      after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6
      months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/
      2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of
      borderline (P=0.058) significance but there was no improvement in lung function.
      In stable patients with COPD, treatment with inhaled budesonide for a period of 6
      months has a positive effect on markers of lung inflammation, as assessed by
      reduction in percentage neutrophils and IL-8 concentration in BAL.

PMID- 15946835
TI  - Ecological association between scarlet fever and asthma.
AB  - One plausible explanation for the worldwide epidemic increase of asthma
      prevalence is the hygiene hypothesis, which suggests that better control of
      infections shifts the immune response toward an allergic phenotype. However,
      studies demonstrating an inverse association between asthma and infectious
      diseases are scarce and possess conflicting results. To explore the relationship
      between asthma and scarlet fever, an ecological analysis of their national trends
      was carried out. Association of both diseases in their annual (1996-2003),
      seasonal (by month) and geographic (by state) trends was evaluated using the
      Spearman's correlation coefficient (r(S)). Results showed a strong inverse
      association between asthma and scarlet fever in all settings. Thus, annual
      incidence rates of both diseases showed an r(S)=-0.93 (P=0.0009). Seasonal
      patterns showed a higher proportion of new asthma cases from September to
      January, while the number of scarlet fever cases increased from March to June
      (r(S)=-0.84, P=0.0006, 1-month lag). Among the 32 Mexican states, the higher the
      incidence of scarlet fever the lower the incidence of asthma (r(S)=-0.47,
      P=0.007). These results suggest that Streptococcus pyogenes, the causative agent
      of scarlet fever, might be one of the major protagonists of the hygiene
      hypothesis, a possibility deserving of further investigation.

PMID- 15946836
TI  - Pulmonary amyloid and PET scanning.

PMID- 15946837
TI  - Siting MSW landfills with a spatial multiple criteria analysis methodology.
AB  - The present work describes a spatial methodology which comprises several methods
      from different scientific fields such as multiple criteria analysis, geographic
      information systems, spatial analysis and spatial statistics. The final goal of
      the methodology is to evaluate the suitability of the study region in order to
      optimally site a landfill. The initial step is the formation of the multiple
      criteria problem's hierarchical structure. Then the methodology utilizes spatial
      analysis processes to create the evaluation criteria, which are mainly based on
      Greek and EU legislation, but are also based on international practice and
      practical guidelines. The relative importance weights of the evaluation criteria
      are estimated using the analytic hierarchy process. With the aid of the simple
      additive weighting method, the suitability for landfill siting of the study
      region is finally evaluated. The resulting land suitability is reported on a
      grading scale of 0-10, which is, respectively, from least to most suitable areas.
      The last step is a spatial clustering process, which is being performed in order
      to reveal the most suitable areas, allowing an initial ranking and selection of
      candidate landfill sites. The application of the presented methodology in the
      island of Lemnos in the North Aegean Sea (Greece) indicated that 9.3% of the
      study region is suitable for landfill siting with grading values greater than 9.

PMID- 15946838
TI  - Effect of sewage sludge or compost on the sorption and distribution of copper and
      cadmium in soil.
AB  - The application of biosolids such as sewage sludge is a concern, because of the
      potential release of toxic metals after decomposition of the organic matter. The
      effect of application of sewage sludge (Sw) and compost (C) to the soil (S) on
      the Cu and Cd sorption, distribution and the quality of the dissolved organic
      matter (DOM) in the soil, was investigated under controlled conditions. Visible
      spectrophotometry, infrared spectroscopy, sorption isotherms (simple and
      competitive sorption systems), and sequential extraction methods were used. The
      E4/E6 (lambda at 465 and 665 nm) ratio and the infrared spectra (IR) of DOM
      showed an aromatic behaviour in compost-soil (C-S); in contrast sewage sludge
      soil (Sw-S) showed an aliphatic behaviour. Application of either Sw or C
      increased the Cu sorption capacity of soil. The Cd sorption decreased only in
      soil with a competitive metal system. The availability of Cu was low due to its
      occurrence in the acid soluble fraction (F3). The Cu concentration varied in
      accordance with the amounts of Cu added. The highest Cd concentration was found
      in the exchangeable fraction (F2). The Sw and C applications did not increase the
      Cd availability in the soil.

PMID- 15946839
TI  - Medical waste management in Jordan: a study at the King Hussein Medical Center.
AB  - As in many other developing countries, the generation of regulated medical waste
      (RMW) in Jordan has increased significantly over the last few decades. Despite
      the serious impacts of RMW on humans and the environment, only minor attention
      has been directed to its proper handling and disposal. This study was conducted
      in the form of a case study at one of Jordan's leading medical centers, namely,
      the King Hussein Medical Center (KHMC). Its purpose was to report on the current
      status of medical waste management at KHMC and propose possible measures to
      improve it. In general, it was found that the center's administration was
      reasonably aware of the importance of medical waste management and practiced some
      of the measures to adequately handle waste generated at the center. However, it
      was also found that significant voids were present that need to be addressed in
      the future including efficient segregation, the use of coded and colored bags,
      better handling and transfer means, and better monitoring and tracking
      techniques, as well as the need for training and awareness programs for the
      personnel.

PMID- 15946841
TI  - A double exponential model for biochemical oxygen demand.
AB  - Biochemical oxygen demand (BOD) exertion patterns in anaerobically treated farm
      dairy wastewater were investigated on a laboratory scale. Oxygen uptake was
      typically characterised by a period of rapid oxygen exertion, a transitional
      "shoulder" phase and a period of slower activity. A multi-species model,
      involving rapidly degradable and slowly degradable material, was developed,
      leading to a double exponential model of BOD exertion as follows:where t is time,
      BOD(u1)(') and BOD(u2)(') are apparent ultimate BOD (BOD(u)) values, and k(1) and
      k(2) are rate constants. The model provided an improved description of BOD
      exertion patterns in anaerobically treated farm dairy wastewater in comparison to
      a conventional single exponential model, with rapidly degradable rate constant
      values (k(1)) ranging from 2.74 to 17.36d(-1), whilst slowly degradable rate
      constant values (k(2)) averaged 0.25d(-1) (range 0.20-0.29). Rapidly and slowly
      degradable apparent BOD(u) estimates ranged from 20 to 140g/m(3) and 225 to
      500g/m(3), respectively, giving total BOD(u) levels of 265-620g/m(3). The mean
      square error in the curve fitting procedure ranged between 20 and 60g(2)/m(6),
      with values on average 70% lower (range 31-91%) than those obtained for the
      single exponential model. When applied to existing data for a range of other
      wastewaters, the double exponential model demonstrated a superior fit to the
      conventional single exponential model and provided a marginally better fit than a
      mixed order model. It is proposed that the presence of rapidly degradable
      material may be indicated from the value of the first rate constant (k1) and the
      time to 95% saturation of the first exponential function. Further model
      development is required to describe observed transitional and lag phases.

PMID- 15946840
TI  - Detection of bacterial toxins with monosaccharide arrays.
AB  - A large number of bacterial toxins, viruses and bacteria target carbohydrate
      derivatives on the cell surface to attach and gain entry into the cell. We report
      here the use of a monosaccharide-based array to detect protein toxins. The array
      based technique provides the capability to perform simultaneous multianalyte
      analyses. Arrays of N-acetyl galactosamine (GalNAc) and N-acetylneuraminic acid
      (Neu5Ac) derivatives were immobilized on the surface of a planar waveguide and
      were used as receptors for protein toxins. These arrays were probed with
      fluorescently labeled bacterial cells and protein toxins. While Salmonella
      typhimurium, Listeria monocytogenes, Escherichia coli and staphylococcal
      enterotoxin B (SEB) did not bind to either of the monosaccharides, both cholera
      toxin and tetanus toxin bound to GalNAc and Neu5Ac. The results show that the
      binding of the toxins to the carbohydrates is density dependent and semi
      selective. Both toxins were detectable at 100 ng/ml.

PMID- 15946842
TI  - Carboxylate bioisosteres of gabapentin.
AB  - A series of carboxylate bioisosteres of structures related to gabapentin 1 have
      been prepared. When the carboxylate was replaced by a tetrazole, this group was
      recognized by the alpha2-delta protein. Further characterization of alpha2-delta
      binding compounds 14a and 14b revealed a similar pattern of functional in vitro
      and in vivo activity to gabapentin 1.

PMID- 15946843
TI  - Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the
      treatment of depression and anxiety.
AB  - Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are
      presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1)
      receptor antagonists. In this paper, we report the affinity and SAR of a series
      of compounds, as well as pharmacokinetic characterization of a chosen set. The
      anxiolitic activity of a selected example (2ba) in the rat pup vocalization model
      is also presented.

PMID- 15946844
TI  - RGD mounted on an L-proline scaffold.
AB  - The construction of an L-proline scaffold that enforces a defined beta-turn loop
      for RGD is reported. A key feature was the use of SASRIN (super acid sensitive
      resin) that allowed solid-phase synthesis of the tetrapeptide. A HATU-induced
      cyclization of the sequence was successful, followed by a single acid-promoted
      deprotection of the final product.

PMID- 15946845
TI  - 4,4'-Dimethoxytrityl group derived from secondary alcohols: are they removed
      slowly under acidic conditions?
AB  - Removal of 4,4'-dimethoxytrityl (DMT) groups from primary and secondary hydroxyl
      functionality was investigated. It was observed that deblocking of DMT group from
      secondary hydroxyl group of molecules attached to solid support under acidic
      conditions occurred relatively slowly compared to primary hydroxyl group.
      Marginal difference in rate of detritylation was observed between DMT group
      attached to 5'-hydroxyl group of deoxyribonucleoside and 2'-O
      methoxyethylribonucleoside when attached to one kind of support. Removal of DMT
      from nucleoside attached to OligoPrep solid support was found to be slow.

PMID- 15946846
TI  - Chromokinesins: multitalented players in mitosis.
AB  - Molecular motors generate cellular forces and act in a multitude of intracellular
      transport processes. The chromokinesins are a subgroup of kinesin motors.
      Chromokinesins act in various steps of mitosis, including chromosome
      condensation, metaphase alignment, chromosome segregation, cytokinesis and they
      help maintain genome stability. The emerging multifunctional nature of the
      chromokinesins provides insights into the coordination of distinct mitotic steps,
      and their role in maintenance of genome stability makes them attractive potential
      targets for therapeutic intervention.

PMID- 15946847
TI  - Foot orthoses affect frequency components of muscle activity in the lower
      extremity.
AB  - The purpose of this study was to quantify the effects of selected foot orthoses
      on muscle activity in the lower extremity during running. Nine male and 12 female
      recreational runners, clinically and functionally classified as 'pronators',
      volunteered for this study and performed over-ground running trials at 4m/s in
      each of four experimental conditions: control, posting, molding, and posting &
      molding. Electromyographic (EMG) signals were recorded from seven lower extremity
      muscles. Wavelet analysis was performed to obtain EMG intensities in two
      frequency bands that were averaged for the pre-heel-strike and post-heel-strike
      intervals and for 30-100% of stance phase. Posting and custom-molding of foot
      orthoses increased the global EMG intensity of most muscles of the lower
      extremity for the stance phase of running (P < 0.05). The increases in EMG
      intensity were greater in the high- than in the low-frequency bands for some
      lower extremity muscles (P < 0.05). The effects on muscle activity of posting and
      custom-molding of foot orthoses differed between the three phases of running
      gait. The three tested foot orthoses did affect lower extremity muscle activity
      differently and these effects were specific to the phases of running gait.
      Combinations of increased requirements of controlling joint motion and minimizing
      soft tissue vibrations may have led to greater increases in shank muscle activity
      for the posted condition. The substantial changes in EMG due to orthotic
      interventions found in this study documents the importance of the study of muscle
      activity as a reaction to shoe inserts and foot orthoses.

PMID- 15946848
TI  - A solid-phase approach to novel purine and nucleoside analogs.
AB  - This paper describes a method for the preparation of purine analogs using the
      solid-phase approach. Nucleoside bases were constructed on Merrifield resin by
      sequential displacement of purine dichloride with amines, and after detachment,
      the purine analogs were condensed with d,l-ribofuranoside compounds by the
      Vorbruggen method. Thereof, l-ribofuranoside was prepared from l-arabinose via
      the selective oxidation-reduction procedure of the 2-OH group. Some compounds
      exhibited moderate activity against HIV-1 in PBM cells.

PMID- 15946849
TI  - Protonated structures of naturally occurring deoxyribonucleic acids and their
      interaction with berberine.
AB  - Protonation-induced conformational changes in natural DNAs of diverse base
      composition under the influence of low pH, low temperature, and low ionic
      strength have been studied using various spectroscopic techniques. At pH3.40,
      10mM [Na+], and at 5 degrees C, all natural DNAs irrespective of base composition
      adopted an unusual and stable conformation remarkably different from the
      canonical B-form conformation. This protonated conformation has been
      characterized to have unique absorption and circular dichroic spectral
      characteristics and exhibited cooperative thermal melting profiles with decreased
      thermal melting temperatures compared to their respective B-form counterparts.
      The nature of this protonated structure was further investigated by monitoring
      the interaction of the plant alkaloid, berberine that was previously shown from
      our laboratory to differentially bind to B-form and H(L)-form of poly[d(G-C)]
      [Bioorg. Med. Chem.2003, 11, 4861]. Binding of berberine to protonated
      conformation of natural DNAs resulted in intrinsic circular dichroic changes as
      well as generation of induced circular dichroic bands for the bound berberine
      molecule with opposite signs and magnitude compared with B-form structures.
      Nevertheless, the binding of the alkaloid to both the B and protonated forms was
      non-linear and non-cooperative as revealed from Scatchard plots derived from
      spectrophotometric titration data. Steady state fluorescence studies on the other
      hand showed remarkable increase of the rather weak intrinsic fluorescence of
      berberine on binding to the protonated structure compared to the B-form
      structure. Taken together, these results suggest that berberine can detect the
      formation of significant population of H(L)-form structures under the influence
      of protonation irrespective of heterogeneous base compositions in natural DNAs.

PMID- 15946850
TI  - Furoxan analogues of the histamine H3-receptor antagonist imoproxifan and related
      furazan derivatives.
AB  - Synthesis and pharmacological characterisation of a series of compounds in which
      the oxime substructure present in imoproxifan was constrained in the pentatomic
      NO-donor furoxan ring, as well as their structurally related furazan analogues
      devoid of NO-donating properties, are described. The whole series of products
      displayed reversible histamine H3-antagonistic activity on guinea-pig ileum. 4-(4
      (3-(1H-Imidazol-4-yl)propoxy)phenyl)furoxan-3-carbonitrile 16 was also able to
      induce partial relaxation when added to the bath after electrical contraction of
      the guinea-pig ileum during the study of its H3-antagonistic properties. This
      phenomenon seems to be dependent on NO-mediated sGC activation. The lipophilic
      hydrophilic balance of all the products was investigated.

PMID- 15946851
TI  - Radioactivity of the Bega sediment-case study of a contaminated canal.
AB  - The Bega canal is one among many heavily polluted canals in Vojvodina (the
      northern province of Serbia and Montenegro). In the framework of the
      revitalization of this canal, the radionuclide content of the sediment was
      investigated in order to support the safe deposition after excavation. It was
      found that, in comparison with the Danube sediment and Vojvodina soil, the Bega
      sediment is contaminated with (238)U and (137)Cs. The origin of this
      contamination is discussed. No traces of contamination by nuclear power plants in
      the region were found, while the presence of technologically enhanced, natural
      occurring radioactive materials (TENORM) was proved.

PMID- 15946852
TI  - The contractile effects of several substituted short analogues of porcine galanin
      in isolated rat jejunal and colonic smooth muscle strips.
AB  - The activity of short porcine galanin (Gal) analogues was tested in vitro using
      rat jejunal and colonic smooth muscle strips. Peptides evoked concentration
      dependent tissue contractions yielding typical response curves in concentration
      range from 0.3 nM to 300 microM, with a characteristic fall-down effect at the
      supramaximal concentrations. Gal(1-15) was less potent than Gal(1-29).
      Furthermore, [D-Trp(2)]Gal(1-15), [endo-Trp(2),Cle(4)]Gal(1-15), [D-Leu(4)]Gal(1
      15), [des-Leu(4)]Gal(1-15), [Hse(6)]Gal(1-15), [Dab(14)]Gal(1-15), [Dpr(14)]Gal(1
      15) or [Arg(14)]Gal(1-15) showed a considerable decrease in potency compared to
      Gal(1-15) in jejunal and/or colonic smooth muscle cells. Functional evidence
      confirmed that the integrity of both N- and C-terminals must be preserved in
      order to preserve a full excitatory myogenic potential of the peptide in rat
      jejunum and colon. Besides, amino acids located in positions 2, 4, 6 and 14 play
      a crucial role in recognition and activation of molecular domains responsible for
      Gal action in the intestinal smooth muscle.

PMID- 15946853
TI  - Heterogeneity of thymic dendritic cells.
AB  - Thymus is the site of generation and selection of T-lymphocytes. It also contains
      phenotypically and functionally distinct dendritic cell (DC) populations,
      including conventional DC (cDC) and plasmacytoid DC (pDC). Thymic cDC are
      heterogeneous and contain two subsets: a major subset derived from the precursors
      within thymus, and a minor subset presumably of extrathymic origin. Increasing
      evidence suggest that thymic cDC can cross-present self-antigens to developing
      thymocytes and play an important role in thymocyte negative selection and central
      tolerance induction. Thymic pDC can produce type-I interferon upon appropriate
      activation. However, their role in a steady state thymus is currently unclear.

PMID- 15946854
TI  - Life cycle, migration and antigen presenting functions of spleen and lymph node
      dendritic cells: limitations of the Langerhans cells paradigm.
AB  - The phenotypic and functional studies carried out in recent years on dendritic
      cells (DC) purified from spleen and lymph nodes has revealed the existence of
      heterogeneous populations with distinct life cycles, migratory properties and
      antigen presenting functions. A major subdivision can be made between "tissue
      derived" DC that migrate to the lymph nodes from peripheral tissues, both in the
      steady state and in the course of infections, and "blood-derived" DC, which
      reside in the spleen and lymph nodes throughout their life cycle. These two
      groups of DC can be subdivided into smaller subsets. The tissue-derived and the
      blood-derived DC also show fundamental differences in maturational status and
      antigen presenting capabilities. In this review, we summarize the roles played by
      the different DC types in the steady state and during pathogen infections,
      relating those roles to maintenance of peripheral tolerance and the induction of
      immunity. We point out the caveats of assuming that the DC that collect antigens
      are the ones involved in their presentation, emphasizing the phenomenon of
      antigen transfer as an important component of the immune response.

PMID- 15946855
TI  - The N-end rule ubiquitin-conjugating enzyme, HR6B, is up-regulated by nerve
      growth factor and required for neurite outgrowth.
AB  - Neurite outgrowth is accompanied by increased levels of high molecular weight
      ubiquitin conjugates and decreased levels of free ubiquitin. The search for
      enzymes responsible for increased utilization of ubiquitin revealed the ubiquitin
      conjugating enzyme, HR6B (yeast UBC2/RAD6), increased on mRNA and protein level
      in rat pheochromocytoma (PC12) cells after treatment with nerve growth factor
      (NGF). HR6B participates in 'N-end rule degradation' that is implicated in the
      cleavage of proteins with destabilizing N-terminal residues (bulky hydrophobic or
      basic amino acids) and requires UBR1, the ubiquitin ligase binding N-end rule
      target proteins. Down-regulation of HR6B or UBR1 mRNA by small interfering RNA
      and treatment with Leu--Ala, a dipeptide-inhibitor of UBR1, inhibit neurite
      outgrowth of PC12 cells. Furthermore, axonal regeneration of adult sensory
      neurons, which express prominent nuclear and membrane-associated HR6
      immunoreactivity, is reduced by Leu--Ala in vitro. Therefore, N-end rule
      ubiquitination is required for neuronal differentiation of PC12 cells and may be
      involved in axonal regeneration of peripheral neurons.

PMID- 15946856
TI  - Neurotractin/kilon promotes neurite outgrowth and is expressed on reactive
      astrocytes after entorhinal cortex lesion.
AB  - The IgLON subgroup of the immunoglobulin superfamily consists of four members
      that are thought to be important in neural cell-cell recognition. Here, we cloned
      and characterized the murine IgLON subgroup member neurotractin/kilon, in the
      context of brain development and axonal regeneration. Neurotractin/kilon was
      found to be upregulated during brain development and is expressed on neurites of
      primary hippocampal neurons. To elucidate a potential role for neurotractin/kilon
      during regeneration in the CNS, we performed lesions in the entorhinal cortex,
      and showed that the expression of neurotractin/kilon is induced on reactive
      astrocytes. Notably, the expression on reactive astrocytes appears specifically
      in the denervated outer molecular layer of the dentate gyrus, where regenerative
      axon sprouting occurs. In vitro assays demonstrated that neurotractin/kilon
      attracts hippocampal axons in the stripe assay and that astroglial
      neurotractin/kilon promotes neurite outgrowth. These results suggest a function
      for neurotractin/kilon as a trans-neural growth-promoting factor for outgrowing
      axons following hippocampal denervation.

PMID- 15946857
TI  - Production, purification, and characterization of human scFv antibodies expressed
      in Saccharomyces cerevisiae, Pichia pastoris, and Escherichia coli.
AB  - Single chain (scFv) antibodies are used as affinity reagents for diagnostics,
      therapeutics, and proteomic analyses. The antibody discovery platform we use to
      identify novel antigen binders involves discovery, characterization, and
      production. The discovery and characterization components have previously been
      characterized but in order to fully utilize the capabilities of affinity reagents
      from our yeast surface display library, efforts were focused on developing a
      production component to obtain purified, soluble, and active scFvs. Instead of
      optimizing conditions to achieve maximum yield, efforts were focused on using a
      system that could quickly and easily produce and process hundreds of scFv
      antibodies. Heterologous protein expression in Saccharomyces cerevisiae, Pichia
      pastoris, and Escherichia coli were evaluated for their ability to rapidly,
      efficaciously, and consistently produce scFv antibodies for use in downstream
      proteomic applications. Following purification, the binding activity of several
      scFv antibodies were quantified using a novel Biacore assay. All three systems
      produced soluble scFv antibodies which ranged in activity from 0 to 99%. scFv
      antibody yields from Saccharomyces, Pichia, and E. coli were 1.5-4.2, 0.4-7.3,
      and 0.63-16.4 mgL(-1) culture, respectively. For our purposes, expression in E.
      coli proved to be the quickest and most consistent way to obtain and characterize
      purified scFv for downstream applications. The E. coli expression system was
      subsequently used to study three scFv variants engineered to determine structure
      function relationships.

PMID- 15946858
TI  - Identification and purification of a soluble region of BubR1: a critical
      component of the mitotic checkpoint complex.
AB  - The mitotic checkpoint complex (MCC) ensures the fidelity of chromosomal
      segregation, by delaying the onset of anaphase until all sister chromatids have
      been properly attached to the mitotic spindle. In essence, this MCC-induced delay
      is achieved via the inhibition of the anaphase-promoting complex (APC). Among the
      components of the MCC, BubR1 plays two major roles in the functions of the
      mitotic checkpoint. First, BubR1 is able to inhibit APC activity, either by
      itself or as a component of the MCC, by sequestering a APC coactivator, known as
      Cdc20. Second, BubR1 activates mitotic checkpoint signaling cascades by binding
      to the centromere-associated protein E, a microtubule motor protein. Obtaining
      highly soluble BubR1 is a prerequisite for the study of its structure. BubR1 is a
      multi-domain protein, which includes a KEN box motif, a mad3-like region, a Bub3
      binding domain, and a kinase domain. We obtained a soluble BubR1 construct using
      a three-step expression strategy. First, we obtained two constructs from BLAST
      sequence homology searches, both of which were expressed abundantly in the
      inclusion bodies. We then adjusted the lengths of the two constructs by secondary
      structure prediction, thereby generating partially soluble constructs. Third, we
      optimized the solubility of the two constructs by either chopping or adding a few
      residues at the C-terminus. Finally, we obtained a highly soluble BubR1 construct
      via the Escherichia coli expression system, which allowed for a yield of 10.8
      mg/L culture. This report may provide insight into the design of highly soluble
      constructs of insoluble multi-domain proteins.

PMID- 15946859
TI  - Phosphorylation of serine residues in histidine-tag sequences attached to
      recombinant protein kinases: a cause of heterogeneity in mass and complications
      in function.
AB  - High-level recombinant expression of protein kinases in eukaryotic cells or
      Escherichia coli commonly gives products that are phosphorylated by autocatalysis
      or by the action of endogenous kinases. Here, we report that phosphorylation
      occurred on serine residues adjacent to hexahistidine affinity tags (His-tags)
      derived from several commercial expression vectors and fused to overexpressed
      kinases. The result was observed with a variety of recombinant kinases expressed
      in either insect cells or E. coli. Multiple phosphorylations of His-tagged full
      length Aurora A, a protein serine/threonine kinase, were detected by mass
      spectrometry when it was expressed in insect cells in the presence of okadaic
      acid, a protein phosphatase inhibitor. Peptide mapping by liquid chromatography
      mass spectrometry detected phosphorylations on all three serine residues in an N
      terminal tag, alpha-N-acetyl-MHHHHHHSSGLPRGS. The same sequence was also
      phosphorylated, but only at a low level, when a His-tagged protein tyrosine
      kinase, Pyk2 was expressed in insect cells and activated in vitro. When catalytic
      domains of Aurora A and several other protein serine/threonine kinases were
      expressed in E. coli, serines in the affinity tag sequence GSSHHHHHHSSGLVPRGS
      were also variably phosphorylated. His-Aurora A with hyperphosphorylation of the
      serine residues in the tag aggregated and resisted thrombin-catalyzed removal of
      the tag. Treatment with alkaline phosphatase partly restored sensitivity to
      thrombin. The same His-tag sequence was also detected bearing alpha-N-d
      gluconoylation in addition to multiple phosphorylations. The results show that
      histidine-tag sequences can receive complicated posttranslational modification,
      and that the hyperphosphorylation and resulting heterogeneity of the recombinant
      fusion proteins can interfere with downstream applications.

PMID- 15946860
TI  - Expression of a synthetic gene encoding a Tribolium castaneum carboxylesterase in
      Pichia pastoris.
AB  - This is the first report of an insect esterase efficiently expressed in the
      methylotrophic yeast Pichia pastoris (so far insect esterases have been produced
      only in the baculovirus system). Having isolated a Tribolium castaneum
      carboxylesterase cDNA (TCE), we were initially unable to express it in
      Escherichia coli or P. pastoris despite significant transcription levels. As
      codon usage bias is different in T. castaneum and P. pastoris, we assumed this
      was a possible explanation for the translational barrier observed in yeast.
      Accordingly, we designed and constructed by recursive PCR a synthetic TCE gene
      (synTCE) optimized for heterologous expression in P. pastoris, i.e., a gene in
      which certain TCE codons are replaced with synonymous codons 'preferred' in P.
      pastoris. When the altered gene was placed under the control of either the P.
      pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter or the inducible
      alcohol oxidase (AOX1) promoter and introduced on an expression vector into P.
      pastoris, its product was produced intracellularly. We also successfully explored
      the possibility of obtaining a secreted product: P. pastoris cells expressing an
      in-frame fusion of synTCE with the alpha-factor secretion signal under the
      control of the GAP promoter were found to secrete the recombinant esterase into
      the external medium (to a concentration of 7 mg/L). In addition to this
      demonstration of TCE production in yeast, our results suggest that the GAP
      promoter could advantageously replace the AOX1 promoter as a driver of synTCE
      expression. TCE specific activity was approximately 5 U/mg when p-nitrophenyl
      acetate was used as substrate.

PMID- 15946861
TI  - Advantages of CCD detectors for de novo three-dimensional structure determination
      in single-particle electron microscopy.
AB  - For three-dimensional (3D) structure determination of large macromolecular
      complexes, single-particle electron cryomicroscopy is considered the method of
      choice. Within this field, structure determination de novo, as opposed to
      refinement of known structures, still presents a major challenge, especially for
      macromolecules without point-group symmetry. This is primarily because of
      technical issues: one of these is poor image contrast, and another is the often
      low particle concentration and sample heterogeneity imposed by the practical
      limits of biochemical purification. In this work, we tested a state-of-the art 4
      k x 4 k charge-coupled device (CCD) detector (TVIPS TemCam-F415) to see whether
      or not it can contribute to improving the image features that are especially
      important for structure determination de novo. The present study is therefore
      focused on a comparison of film and CCD detector in the acquisition of images in
      the low-to-medium ( approximately 10-25 A) resolution range using a 200 kV
      electron microscope equipped with field emission gun. For comparison, biological
      specimens and radiation-insensitive carbon layers were imaged under various
      conditions to test the image phase transmission, spatial signal-to-noise ratio,
      visual image quality and power-spectral signal decay for the complete image
      processing chain. At all settings of the camera, the phase transmission and
      spectral signal-to-noise ratio were significantly better on CCD than on film in
      the low-to-medium resolution range. Thus, the number of particle images needed
      for initial structure determination is reduced and the overall quality of the
      initial computed 3D models is improved. However, at high resolution, film is
      still significantly better than the CCD camera: without binning of the CCD camera
      and at a magnification of 70 kx, film is better beyond 21 A resolution. With 4
      fold binning of the CCD camera and at very high magnification (> 300 kx) film is
      still superior beyond 7 A resolution.

PMID- 15946862
TI  - Rectus femoris surface myoelectric signal cross-talk during static contractions.
AB  - The clinical application of EMG requires that the recorded signal is
      representative of the muscle of interest and is not contaminated with signals
      from adjacent muscles. Some authors report that surface EMG is not suitable for
      obtaining information on a single muscle but rather reflects muscle group
      function [J. Perry, C.S. Easterday, D.J. Antonelli, Surface versus intramuscular
      electrodes for electromyography of superficial and deep muscles. Physical Therapy
      61 (1981) 7-15]. Other authors report however, that surface EMG is adequate to
      determine individual muscle function, once guidelines pertaining to data
      acquisition are followed [D.A. Winter, A.J. Fuglevand, S.E. Archer. Cross-talk in
      surface electromyography: theoretical and practical estimates. Journal of
      Electromyography and Kinesiology 4 (1994) 15-26]. The aim of this study was to
      determine whether surface EMG was suitable for monitoring rectus femoris (RF)
      activity during static contractions. Five healthy subjects, having given written
      informed consent, participated in this trial. Surface and fine wire EMG from the
      rectus femoris and the vastus lateralis (VL) muscles were recorded simultaneously
      during a protocol of static contractions consisting of knee extensions and hip
      flexions. Ratios were used to quantify the relationship between the surface EMG
      amplitude value and the fine wire EMG amplitude value for the same contraction.
      The results showed that hip flexion contractions elicited RF activation only and
      that knee extension contractions elicited fine wire activity in VL only. When the
      relationship between RF surface and RF fine wire electrodes was compared for hip
      flexion and knee extension contractions, it was observed that for all subjects,
      there was a tendency for increased RF surface activity in the absence of RF fine
      wire activity during knee extensions. It was concluded that the activity recorded
      by the RF surface electrode arrangement during knee extension consisted of EMG
      from the vastii, i.e., cross-talk and that vastus intermedius was the most likely
      origin of the erroneous signal. Therefore it is concluded that for accurate EMG
      information from RF, fine wire electrodes are necessary during a range of static
      contractions.

PMID- 15946863
TI  - Attention and emotion: does rating emotion alter neural responses to amusing and
      sad films?
AB  - Functional neuroimaging of affective systems often includes subjective self
      report of the affective response. Although self-report provides valuable
      information regarding participants' affective responses, prior studies have
      raised the concern that the attentional demands of reporting on affective
      experience may obscure neural activations reflecting more natural affective
      responses. In the present study, we used potent emotion-eliciting amusing and sad
      films, employed a novel method of continuous self-reported rating of emotion
      experience, and compared the impact of rating with passive viewing of amusing and
      sad films. Subjective rating of ongoing emotional responses did not decrease
      either self-reported experience of emotion or neural activations relative to
      passive viewing in any brain regions. Rating, relative to passive viewing,
      produced increased activity in anterior cingulate, insula, and several other
      areas associated with introspection of emotion. These results support the use of
      continuous emotion measures and emotionally engaging films to study the dynamics
      of emotional responding and suggest that there may be some contexts in which the
      attention to emotion induced by reporting emotion experience does not disrupt
      emotional responding either behaviorally or neurally.

PMID- 15946864
TI  - Mining the posterior cingulate: segregation between memory and pain components.
AB  - We present a general method for automatic meta-analyses in neuroscience and apply
      it on text data from published functional imaging studies to extract main
      functions associated with a brain area-the posterior cingulate cortex (PCC).
      Abstracts from PubMed are downloaded, words extracted and converted to a bag-of
      words matrix representation. The combined data are analyzed with hierarchical non
      negative matrix factorization. We find that the prominent themes in the PCC
      corpus are episodic memory retrieval and pain. We further characterize the
      distribution in PCC of the Talairach coordinates available in some of the
      articles. This shows a tendency to functional segregation between memory and pain
      components where memory activations are predominantly in the caudal part and pain
      in the rostral part of PCC.

PMID- 15946865
TI  - Molecular phylogeny of Chromodoris (Mollusca, Nudibranchia) and the
      identification of a planar spawning clade.

PMID- 15946866
TI  - Modulation of recognition and temporal order memory retrieval by dopamine D1
      receptor in rats.
AB  - The present study examines the effects of SKF 81297, a selective D1 agonist, on
      information retrieval in recognition and temporal order memory for objects, using
      three different tasks. Separate groups of rats were trained in each task and then
      given an intraperitoneal injection of saline or the D1 agonist (0.03, 0.3 mg/kg),
      before the memory testing trial in an object recognition, object location, and
      object temporal order memory tasks. We show that SKF 81297, at high dose (0.3
      mg/kg), facilitates information retrieval after a long delay (4 h) in the three
      memory tasks whereas both high and low doses of D1 agonist impair recognition
      memory after a short delay (15 min). These results indicate a significant role of
      dopamine D1 receptors in recognition memory for both familiarity and place of
      objects in addition to object temporal order memory.

PMID- 15946867
TI  - Regarding: 'Sapheno-femoral junction reflux in patients with a normal saphenous
      trunk' by N. Labropoulos and coll.

PMID- 15946868
TI  - Exosome release by reticulocytes--an integral part of the red blood cell
      differentiation system.
AB  - Reticulocyte maturation into erythrocytes is the final step of erythropoiesis
      that occurs in the blood circulation. This terminal differentiation period
      corresponds to a cellular remodeling phase following expulsion of the nucleus
      into the bone marrow. Among other events, this remodeling leads to the
      disappearance of intracellular organelles and acquisition of the typical cellular
      biconcave form. Here, we propose that exosome biogenesis and secretion, which
      contributes to net loss of the cell surface membrane via selective vesicular
      membrane secretion, is also closely interconnected with upstream (nucleus
      expulsion), accompanying (mitoptosis) and downstream (vesicle clearance) events.

PMID- 15946869
TI  - Expression of one-hybrid fusions with Staphylococcus aureus lexA in Candida
      albicans confirms that Nrg1 is a transcriptional repressor and that Gcn4 is a
      transcriptional activator.
AB  - In the pathogenic fungus, Candida albicans, Nrg1 down-regulates the expression of
      morphogenetic genes and is presumed to act as a transcriptional repressor. In
      contrast, Gcn4 up-regulates amino acid biosynthetic genes and is presumed to be a
      transcriptional activator. However, these presumptions remain to be tested
      directly. A classic approach has been to use a one-hybrid assay that exploits the
      Escherichia coli lexA protein fusions. However in C. albicans, the alternate
      decoding of CUG as serine prevents the expression of heterologous genes such as
      lexA, which contain numerous CUG codons. Therefore, we have developed a one
      hybrid system, based on the Staphylococcus aureus lexA gene, as a tool for one
      hybrid analyses of transcription factors in C. albicans. Using this one-hybrid
      system we have confirmed directly the positive and negative transcriptional
      activities of Nrg1 and Gcn4 in C. albicans.

PMID- 15946870
TI  - Lacosamide displays potent antinociceptive effects in animal models for
      inflammatory pain.
AB  - Lacosamide is a functionalized amino acid which was initially synthesized as an
      antiepileptic drug. In addition to its broad anti-seizure activity, lacosamide
      was shown to display efficacy in animal models for neuropathic pain and is
      currently in phase III clinical development for the treatment of epilepsy and
      neuropathic pain. In order to further profile its antinociceptive properties, the
      effects of lacosamide on inflammatory pain in the formalin test, the carrageenan
      model and the adjuvant-induced arthritis model were investigated. For the
      formalin test, mice received an intraplantar injection of formalin and the
      subsequent licking response was measured over 45 min. Lacosamide was administered
      30 min before formalin. For the carrageenan model, mechanical and thermal
      hyperalgesia were assessed 3 h following an intraplantar injection of
      carrageenan. Lacosamide was administered to rats 30 min before pain threshold
      measurements. For the adjuvant-induced arthritis test rats received intraplantar
      injections of Freund's complete adjuvant into the right hindpaw which lead to the
      development of arthritic symptoms in all animals tested for antinociception. On
      day 11 after arthritis induction, mechanical hyperalgesia was assessed by the
      modified Randall Selitto paw pressure test following acute treatment with
      lacosamide. Lacosamide dose-dependently attenuated mechanical hyperalgesia
      following carrageenan injection and in rats suffering from Freund's complete
      adjuvant-induced arthritis. Moreover, thermal hyperalgesia induced by carrageenan
      as well as the formalin-induced licking response were dose-dependently attenuated
      by lacosamide. These results suggest lacosamide may be active against various
      forms of acute and chronic inflammatory pain in humans.

PMID- 15946871
TI  - Specific effect of levetiracetam in experimental human pain models.
AB  - BACKGROUND: Levetiracetam is a new antiepileptic drug. There is only limited
      experience with levetiracetam in clinical neuropathic pain. AIM: To test the
      analgesic effect of levetiracetam in a human experimental pain model in order to
      obtain preclinical evidence for its potential effect in neuropathic pain.
      METHODS: Sixteen healthy volunteers completed a randomized, double-blind, cross
      over trial with a single oral dose of 1500 mg levetiracetam against placebo. Pain
      tests included pain detection and tolerance to single electrical stimulation and
      temporal pain summation threshold to repetitive electrical stimulation (3 Hz) of
      the sural nerve. RESULTS: Levetiracetam significantly increased the pain
      tolerance thresholds (p=0.04), and the pain detection thresholds tended to be
      increased (p=0.06), whereas levetiracetam had no effect on temporal pain
      summation thresholds (p=0.30). CONCLUSION: Levetiracetam has an analgesic effect
      in the electrical sural nerve stimulation pain model, but it did not increase
      temporal pain summation threshold. Levetiracetam may still be effective in
      clinical neuropathic pain.

PMID- 15946872
TI  - A daily process design study of attentional pain control strategies in the self
      management of cancer pain.
AB  - This study investigated the use of attentional control strategies in the self
      management of pain using daily process design methodology. Twenty six cancer
      patients with pain completed diaries 3 times daily for 10 days. Diaries
      incorporated measures of pain intensity, affect, coping, coping efficacy, and the
      novelty and predictability of pain, and participants completed a cross-sectional
      measure of catastrophizing. At the across-person level, focusing on pain was
      associated with increased negative affect, and the use of pain focusing
      strategies was positively correlated with experiencing pain that was novel in its
      location or quality. Distractions that were interesting, important and pleasant
      were positively correlated with positive affect, perceptions of control over pain
      and ability to decrease pain. Over-prediction of pain was positively correlated
      with catastrophizing, and negatively correlated with perceptions of control over
      and ability to decrease pain. The within-person analysis (ARIMA modelling) showed
      that catastrophizing moderated the effects of pain focusing strategies, novel
      pain and over-predictions of pain. Meta-analysis of the ARIMA models revealed
      that the within-person effects of using attentional strategies did not generalize
      across the sample. These findings indicated that the effects of distraction
      strategies are influenced by their motivational-affective significance rather
      than the frequency with which they are used, and provided further evidence that
      the threat value of pain influences the way in which people cope with their pain.
      Theoretical and clinical implications are discussed.

PMID- 15946873
TI  - Application of the out-of-phase absorption mode to separating overlapping EPR
      signals with different T1 values.
AB  - The use of 90 degrees-out-of-phase first-harmonic absorption (V1'-) EPR to
      resolve the spectra from nitroxide spin labels with differing T1-relaxation times
      is described. Non-linear V1'-EPR spectra recorded under moderate saturation have
      sharper lines compared with the in-phase V1-EPR spectra, and amplitudes that
      preferentially enhance components with longer T1-relaxation. Discrimination
      between V1'-spectral components can be increased further by means of selective
      paramagnetic relaxation enhancement agents. Examples are given of biophysical
      applications to double labelling in single-component membranes and phase
      separation in two-component membranes, to lipid-peptide complexes, and to binding
      of spin-labelled reagents. It is concluded that optimal resolution in V1'-EPR
      spectroscopy is obtained at relatively low Zeeman modulation frequencies (20-30
      kHz) and moderate saturation (H1 approximately 0.2-0.3 G).

PMID- 15946874
TI  - DENSE with SENSE.
AB  - Displacement encoding with stimulated echoes (DENSE) with a low encoding strength
      phase-cycled meta-DENSE readout and a two fold SENSE acceleration (R = 2) is
      described. This combination reduces total breath-hold times for increased patient
      comfort during cardiac regional myocardial contractility studies. Images from
      phantoms, normal volunteers, and a patient are provided to demonstrate the SENSE
      DENSE combination of methods. The overall breath-hold time is halved while
      preserving strain map quality.

PMID- 15946875
TI  - Spin-edited 2D HSQC-TOCSY experiments for the measurement of homonuclear and
      heteronuclear coupling constants: application to carbohydrates and peptides.
AB  - Simple modifications of the sensitivity-improved HSQC-TOCSY pulse sequence are
      proposed for the easy determination of the sign and the magnitude of homonuclear
      and heteronuclear coupling constants. Whereas in well-resolved regions, a clean
      two-component E.COSY-like pattern allows a direct measurement from a single 2D
      spectrum, separate acquisition of equivalent single-component TROSY/anti-TROSY
      spectra becomes highly interesting when spectral crowding complicates the
      spectral analysis. It is also demonstrated that an additional restricted planar
      mixing element after the isotropic TOCSY process completely retains all spin
      editing features and permits the accurate measurement of the sign and the size of
      the corresponding homonuclear proton-proton coupling constants. Among others, the
      proposed techniques are particularly suited for molecules presenting a great
      number of CH and NH spin systems. Examples and practical details of the
      implementation of these techniques on standard carbohydrates and peptides at 13C
      and 15N natural abundance are provided.

PMID- 15946876
TI  - MathNMR: spin and spatial tensor manipulations in Mathematica.
AB  - Spin and spatial tensor manipulations are frequently required to describe the
      theory of NMR experiments. A Mathematica package is presented here, which
      provides some of the most common functions for these calculations. Examples are
      the calculation of matrix representations of operators, commutators, projections,
      rotations, Redfield matrix elements, matrix decomposition into basis operators,
      change of basis, coherence filtering, and the manipulation of Hamiltonians. The
      calculations can be performed for any spin system, containing spins 1/2 and
      quadrupolar spins alike, subject to computational limitations. The package will
      be available from upon acceptance of the article.

PMID- 15946877
TI  - Effect of body position on ventilatory responses in anaesthetised mice.
AB  - The effects of body position on ventilatory responses to chemical stimuli have
      rarely been studied in experimental animals, despite evidence that position may
      be a factor in respiratory results. The purpose of this study was to test whether
      body position could affect acute ventilatory responses to 4-min periods of
      moderate hypercapnia (5% CO(2) in O(2)) and poikilocapnic hypoxia (15% O(2) in
      N(2)) in the urethane-anaesthetised mouse. Respiratory measurements were
      conducted with mice in the prone and supine positions with a whole-body, single
      chamber plethysmograph. During hypoxia, the time course of minute ventilation (V
      (E)) was similar in the two positions, but the breathing pattern was different.
      After the response peak, V (E) depended on respiratory frequency (f) and tidal
      volume (V(T)) in the prone position but mainly on V(T) in the supine position. In
      the supine position, f declined below the baseline values toward the end of
      hypoxic exposure. During hypercapnia, there were no ventilatory differences
      between the prone and supine positions. Brief hypoxic exposure elicited f
      depression in the supine position in the anaesthetised mouse. The depressive
      effect on f suggests that the supine position may not be optimal for sustaining
      ventilation, particularly during hypoxia.

PMID- 15946878
TI  - Reconstitution of functional nuclear receptor proteins using high pressure
      refolding.
AB  - Members of the nuclear receptor superfamily are ligand dependent transcription
      factors and many of the receptors are difficult to produce in their functional
      form. Here, we describe a method for obtaining functional nuclear receptor ligand
      binding domain proteins from bacterial expressed inclusion bodies by high
      hydrostatic pressure induced refolding. High pressure refolding successfully
      reconstituted activity from several insoluble nuclear receptor proteins and
      represents a valuable tool for both functional and structural investigation of
      proteins or fragments thereof that might otherwise remain insoluble.

PMID- 15946879
TI  - Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the
      Japanese population.
AB  - Inosine triphosphate pyrophosphohydrolase (ITPase) is an enzyme that catalyzes
      the conversion of inosine triphosphate (ITP) to inosine monophosphate and
      pyrophosphate. In Caucasian populations it is reported that the frequency of
      cases showing decreased ITPase activity is 5%. The structure of ITPA gene along
      with five single nucleotide polymorphisms has been reported in Caucasians. We
      examined ITPase activity and frequency of two polymorphisms (94C>A and
      IVS2+21A>C) in 100 Japanese individuals. Among these individuals, we observed
      that three cases with zero activity were homozygote for 94C>A, and were
      accompanied by abnormal accumulation of ITP in erythrocytes. The cases included
      in the low ITPase activity group were heterozygote for 94C>A polymorphism. The
      activity of the heterozygote cases was approximately 27% of the mean value of the
      wild type. The allele frequency of the 94C>A polymorphism was 0.155, which was
      2.6 times higher than that of the Caucasians (0.06). The IVS2+21A>C was not
      detected in Japanese cases, although it occurred with a frequency of 0.130 in
      Caucasians. Furthermore, we identified a novel mutation IVS2+68T>G in intron 2 in
      the case with the lowest enzyme activity in the 94C>A wild type. Since the
      frequency of ITPA 94C>A polymorphism is higher in the Japanese population than
      that in Caucasians, it is more important to examine ITPA 94C>A polymorphism in
      the Japanese population to prevent thiopurine drug toxicity. Pretherapeutic
      screening of individuals for ITPA polymorphisms should be considered for safer
      and more tolerable treatment with thiopurine drugs.

PMID- 15946880
TI  - [The European Network of Transfusion Medicine Societies (EuroNet-TMS)].

PMID- 15946881
TI  - [France and Europe, what are their ambitions?].

PMID- 15946883
TI  - Molecular mechanisms of Lewis antigen expression.
AB  - Lewis antigens comprise type 1 (Lewis a, Lewis b) and type 2 (Lewis X, Lewis Y)
      carbohydrates. Lewis X and Lewis Y are regarded as tumor-associated markers, and
      some of these antigens and their derivatives interact with selectins, mediating
      cell-to-cell adhesion. In addition, Lewis b on the gastric epithelial surface has
      been identified as an acceptor for attachment of Helicobacter pylori. In this
      review, we describe the regulation the expression of type 1 Lewis antigens on
      erythrocytes or digestive organs by two genes (FUT2 and FUT3), and the ethnic
      specificity of the polymorphism of these genes for forensic use.

PMID- 15946882
TI  - [Hypothyroidism following cervical irradiation in the management of carcinoma of
      the nasopharynx and of the breast: a prospective study on eighty-four cases].
AB  - PURPOSE: 1/ To evaluate the incidence of hypothyroidism following radiotherapy in
      the management of breast and nasopharyngeal carcinomas, 2/ to define the role of
      a systematic post therapeutic screening. PATIENTS AND METHODS: From January 1996
      through March 2001 a systematic evaluation of the clinical and the biological
      thyroid function was performed on a cohort of 84 patients that received
      supraclavicular irradiation. Selected patients had either a mammary (37 cases) or
      a nasopharyngeal (47 cases) carcinoma. Initial work up included thyroid
      inspection and palpation, and biological tests: serum FT4 and TSH levels,
      radioimmunochemistry, completed by dynamic thyroid stimulation, using TRH, in
      case of border line low T4 or isolated high TSH levels. Tests were repeated every
      three months the first year, and then every six months. Replacement therapy with
      L Thyroxin was administered in case of hypothyroidism. RESULTS: All selected
      patients had a normal function initially. With a mean two years follow up (1-5
      years), 24 patients (29%) experienced hypothyroidism, half of whom (13 cases)
      being purely biological. Five patients (11%), with a nasopharyngeal carcinoma,
      presented also with associated pituitary failure. Clinical symptoms were minor or
      mild in all cases. Hypothyroidism was detected at a mean 21 months follow up. In
      2 patients, hypothyroidism disappeared spontaneously within 6 months. Possible
      predictive factors were evaluated: age of the time of radiation, gender,
      percentage of irradiated thyroid, total dose, dose per fraction, tumour type and
      chemotherapy. Only age appeared significantly correlated with thyroid dysfunction
      (range: 10-30 years, P=0.002). CONCLUSION: Hypothyroidism is a frequent and
      certainly underestimated complication following radiotherapy of the neck. In such
      patients, a systematic clinical and biological evaluation every three months the
      first year, and then every six months until five years is recommended.

PMID- 15946884
TI  - Effects of perimortem physical factors associated with death on exogenous ethanol
      concentrations in cardiac blood.
AB  - The purpose of this study was to determine whether perimortem physical factors
      associated with death affect exogenous ethanol concentrations in cardiac blood.
      Forty-one autopsies of alcohol-intoxicated decedents with no or little
      putrefaction were involved. Postmortem intervals ranged from 6 to 96 h at the
      time of autopsy. Our 41 cases consisted of 17 fire victims, 8 drowned persons, 3
      blood-loss patients who underwent unsuccessful cardiopulmonary resuscitation
      (CPR) for 30-50 min, 3 blood-loss persons without CPR, three non-blood-loss
      patients who underwent unsuccessful CPR for 5-60 min, and seven people who died
      of other causes. Ethanol concentrations in right cardiac chamber blood ranged
      from 0.12 to 4.40 mg/g (mean 1.39 mg/g) in all cases. An excellent correlation
      was observed between ethanol concentrations in right cardiac chamber blood and
      femoral venous blood (y=1.01x-0.087, n=38, r2=0.990). The ratios of blood ethanol
      concentrations in the left to right cardiac chambers were significantly lower in
      blood-loss decedents with CPR (0.71+/-0.13) than other decedents (0.92+/-0.07
      1.06+/-0.06). Two factors, blood-loss and prolonged chest compression under
      ventilation, might have caused a decrease in blood ethanol concentration in the
      left cardiac chambers. Postmortem cardiac blood ethanol concentration as well as
      postmortem femoral venous blood ethanol concentration may usually reflect blood
      ethanol levels at the time of death when putrefaction is not evident. However,
      special attention is required for cases that received CPR after massive bleeding.

PMID- 15946885
TI  - Molecular aspects of Rh antigens.
AB  - Since the cloning of two Rh related cDNAs, several attempts to clarify the
      molecular basis of Rh system have been performed. The RHD gene is deleted in most
      Caucasians who lack the D antigen, whereas some Japanese RhD(-) individuals
      appear to have an intact RHD gene. The expression study in erythroleukemic cells
      revealed that c and E antigens were expressed on a single polypeptide encoded by
      a full length cE transcript and RhD transcript give rise to D and G antigens.
      Recent finishing of human genome euchromatin sequencing confirmed the genomic
      organization of RH locus in which RHD and CE face each other at their 3' tails,
      and the gene SMP1 is interspersed between them. Two 9 kb transposon-like DNA
      segments, called 'rhesus boxes' were identified in both upstream and downstream
      of the RHD gene. Murine genome sequence of rh locus indicate not only the ancient
      duplication of RH gene by the mechanism of retro-transposition before hominoids
      branched off but also the unequal crossing over at the 'rhesus boxes' resulting
      in an RHD deletion. The macrocomplex formed by Rh, RhAG and band3 is thought
      contributing for the physiological functions, anchoring lipid bilayer to spectrin
      based framework and membrane transportation of CO2 and HCO3-.

PMID- 15946886
TI  - Clinical applications of DNase I, a genetic marker already used for forensic
      identification.
AB  - This review primarily summarizes the clinical applications of deoxyribonuclease I
      (DNase I). Human DNase I exhibits polymorphism at both the protein and DNA level,
      and thus is potentially one of the best biochemical markers for forensic
      practice. Clinically, DNase I activity in serum can be used as a novel diagnostic
      marker for the early detection of acute myocardial infarction and transient
      myocardial ischemia. Furthermore, the DNase I gene is considered to be one of the
      susceptibility genes for gastric and colorectal carcinoma, and myocardial
      infarction. Over the last decade since the discovery of the utility of its
      genetic polymorphism for forensic purposes, research on DNase I has expanded into
      clinical applications.

PMID- 15946887
TI  - Molecular aspects of biochemical markers.
AB  - This review summarizes present knowledge of the molecular basis for certain serum
      protein and red cell enzyme markers that have played important roles in forensic
      individualization and paternity tests. Most genes have nucleotide variations at
      two or more mutations sites, and their alleles exist as haplotypes. Allelic
      diversity is generated by various mechanisms including point mutation, intragenic
      recombination, gene conversion, and alternative splicing. Deficient and null
      alleles arise from point mutation and deletion. The value of genomic information
      on allelic diversity is also discussed.

PMID- 15946888
TI  - Detection of single nucleotide polymorphism in the FUT2 gene by temperature
      gradient gel electrophoresis.
AB  - A simple and rapid analysis system for single nucleotide polymorphisms (SNPs) was
      investigated for the FUT2 gene using the temperature gradient gel electrophoresis
      (TGGE) method. The 426-bp or 259-bp FUT2 fragments were amplified from
      heterozygous samples using primers, and the heteroduplex and homoduplex bands
      were detected by TGGE. The FUT2 fragments amplified from homozygous samples were
      denatured and re-annealed with a known sequence fragment, forming heteroduplex
      bands which were analyzed by TGGE. The fragment patterns of homoduplex and
      heteroduplex bands in TGGE were specific to the genotypes, and more specifically,
      the number of heteroduplex bands and the migration of the homoduplex bands
      corresponded to the number of nucleotide substitutions and the change in GC
      content due to the substitutions, respectively. Thus, the TGGE technique can act
      as a high-throughput method for the detection and the presumption of sequences of
      known and unknown SNPs in the FUT2 gene.

PMID- 15946889
TI  - Cell forces in tissues.
AB  - This articles reviews the measurement, the effects and the biological importance
      of forces that cells exert on each other. It does not review the effects of
      forces originating from movement of tissues, muscular activity, movement and
      gravity.

PMID- 15946890
TI  - Time-dependent analysis of leaflets in mechanical aortic bileaflet heart valves
      in closing phase using the finite strip method.
AB  - BACKGROUND AND AIMS OF THE STUDY: Mechanical heart valves (MHV) are widely used
      to replace dysfunctional and failed heart valves. The bileaflet MHV design is
      very popular due to its superior hemodynamics. Since their introduction in 1977,
      the hemodynamics of bileaflet prostheses has been extensively studied. In this
      study the dynamic behaviour during the closing phase of a bileaflet MHV under
      normal physiological conditions has been investigated. METHODS: Fluid analysis is
      based on the control volume with moving boundaries in the vicinity of the
      occluder. Unsteady continuity equation, unsteady momentum equation on the control
      volume and unsteady Bernoulli's equation have been used to calculate velocity of
      blood flow and force on the occluder tip. To solve the governing equations for
      the calculation of pressure and the related force, the finite strips method has
      been implemented. Only 32 strips are sufficient to calculate the force due to
      pressure on the leaflets. The equations of motion have been solved using the
      Runge-Kutta method in the fourth order. RESULTS: The maximum velocity of the
      leakage flow in the closing phase falls within the range of 3.5-4.4 m/s. The
      maximum velocity of the occluder tip is in the range of 2.4-3.2 m/s. The backflow
      also exhibits oscillation similar to that of the occluder with net backflow rate
      in the range of 9.7-12.3 ml/beat. The impact force between occluder and its
      housing is in the range of 80-140 N and impact occurs during 33.1-41.0 ms and the
      leaflets are completely settled at 108-115 ms in the closing phase. CONCLUSION:
      The finite strip method was implemented to study the closing phase of a bileaflet
      MHV. Results are consistent with the previous experimental data. This method is
      of general applicability to study dynamic behaviour of MHVs.

PMID- 15946891
TI  - MTP1 mops up excess zinc in Arabidopsis cells.
AB  - The MTP1 protein of Arabidopsis thaliana belongs to a ubiquitous family of
      transition metal transporters that extrude metal ions from the cytoplasm. In a
      recent publication, Yoshihiro Kobae and colleagues show that AtMTP1 localizes to
      the vacuolar membrane in Arabidopsis roots and suspension-cultured cells. They
      demonstrate that the mtp1-1 mutant is hypersensitive to zinc and complement the
      mutant by transforming it with the MTP1 coding sequence downstream of a
      constitutive (35S) promoter.

PMID- 15946892
TI  - The role of caspases in cell death and differentiation.
AB  - The complexity, redundancy and interdependence of the biological systems involved
      in tumour response to different treatments hamper progress towards developing
      specific and effective therapies. In addition, the many and even contradictory
      roles played by certain key proteins can significantly amend our view on
      tumourigenesis. The role of caspases in the modulation of cell death and
      differentiation is a prominent example of such a complexity. Here we focus on the
      role of caspases in apoptotic cell death, mainly in haematological malignancies,
      tumourigenesis, sepsis, T-cell proliferation and cell differentiation.

PMID- 15946893
TI  - Symbiosis between grasses and asexual fungal endophytes.
AB  - The symbiosis between vertically transmitted asexual endophytic fungi and grasses
      is common and generally considered to be mutualistic. Recent studies have
      accumulated evidence of negative effects of endophytes on plant fitness,
      prompting a debate on the true nature of the symbiosis. Genetic factors in each
      of the two partners show high variability and have a range of effects (from
      positive to negative) on plant fitness. In addition, interacting environmental
      factors might modify the nature of the symbiosis. Finally, competition and
      multitrophic interactions among grass consumers are influenced by endophytes, and
      the effects of plant neighbours or consumers could feedback to affect plant
      fitness. We propose a mutualism-parasitism continuum for the symbiosis between
      asexual endophytes and grasses, which is similar to the associations between
      plants and mycorrhizal fungi.

PMID- 15946894
TI  - Gene profiling of laser-microdissected brain regions and sub-regions.
AB  - The application of transcriptomics and proteomics approaches to accurately
      dissected anatomically-defined brain regions and sub-regions remains a central
      focus of current neurobiological investigations as well as a necessary step
      towards single-neuron neurogenomics and neuroproteomics. A protocol is described
      for the simple, rapid, and reproducible laser microdissection of brain regions
      and sub-regions for microarray-based gene expression analyses from individual
      rats or mice using two rounds of in vitro transcription (IVT). The results
      presented also demonstrate that the current Affymetrix GeneChip arrays are well
      suited for this experimental design with high reproducibility and limited effects
      of the shortening of target RNA caused by the double IVT approach.

PMID- 15946895
TI  - Scaled quantum chemical calculations and FTIR, FT-Raman spectral analysis of 3,4
      diamino benzophenone.
AB  - The vibrational spectra of 3,4-diamino benzophenone (DABP) have been computed
      using B3LYP methodology and 6-31G* and 6-31G** basis sets. The solid phase FTIR
      and FT-Raman spectra were recorded in the region 4000-400 cm-1 and 3500-100 cm-1,
      respectively. A close agreement was achieved between the observed and calculated
      frequencies by employing normal coordinate calculations. The observed and
      simulated spectra were found to be well comparable.

PMID- 15946896
TI  - Erectile dysfunction, obstructive sleep apnea syndrome and nasal CPAP treatment.
AB  - BACKGROUND AND PURPOSE: To evaluate the effect of one month of continuous
      positive airway pressure (CPAP) in a subgroup of obstructive sleep apnea (OSA)
      patients with erectile dysfunction (ED) and compare this subgroup with age- and
      body mass index (BMI)-matched OSA patients without ED. PATIENTS AND METHODS:
      Prospective general, sleep, psychiatric and sexologic evaluations were conducted.
      Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI), Sleep Disorders
      Questionnaire (SDQ), Quality of Life SF-36, and polysomnography were used.
      Seventeen OSA patients with ED were compared prior to CPAP treatment and during
      CPAP treatment with age- and BMI-matched OSA patients without ED. Parametric and
      non-parametric statistics, chi-square, Fisher exact test and multiple regression
      analyses were performed. RESULTS: Ninety-eight men (BMI=28.8 kg/m2, apnea
      hypopnea index (AHI)=49.6 events/h, ESS=14.8, BDI=8.4, and lowest SaO2=75.3%)
      were divided into subgroups of lowest SaO2>80% (A) and lowest SaO2< or =80% (B).
      (A) Forty-six men had a mean lowest SaO2 of 85.7%+/-2.9, AHI=29.5+/-17.6,
      age=46.3+/-9.3 years, ESS=13.6+/-4.2, BMI=25.8+/-4.8. Seven of the patients had
      ED. (B) Fifty-two men had a mean lowest SaO2=60.10+/-10.0%, AHI=67.4+/-24.5,
      BDI=9.0+/-6.9, age=47.4+/-9.4 years, ESS=16.2+/-4.4, BMI=31.4+/-5.1. Twenty-one
      of the patients had ED (chi2: P=0.006). Significant variables for ED were lowest
      SaO2 and age (r=0.17). CPAP-treated subgroup: ED subjects had significantly lower
      SaO2, ESS, BDI and SF-36 subscale scores than OSA controls. Nasal CPAP eliminated
      the differences between groups, and ED was resolved in 13 out of 17 cases.
      CONCLUSIONS: ED in OSAS is related to nocturnal hypoxemia, and about 75% of OSAS
      patients with ED treated with nasal CPAP showed remission at one-month follow-up,
      resulting in significant improvement in quality of life.

PMID- 15946897
TI  - Progressive sleep 'destructuring' in Parkinson's disease. A polysomnographic
      study in 46 patients.
AB  - BACKGROUND: Sleep abnormalities in Parkinson's disease (PD) are frequent, but it
      is unknown whether or not there is progressive loss of physiological sleep
      architecture or what the causes could be. METHODS: Retrospective review of
      medical records and polysomnographic data from 46 non-demented PD patients.
      RESULTS: Sleep latency was correlated with disease duration (F1,44=4.87, P=0.03).
      Total sleep time (F1,44=8.54, P=0.005), deep sleep time (F1,44=4.06, P=0.05), REM
      sleep time (F1,44=9.15, P=0.004) and sleep efficiency (SE) (F1,44=10.20, P=0.003)
      were inversely correlated with disease duration. The same sleep parameters were
      independent from the degree of motor impairment, dosage of the dopaminergic
      medications, and age. Subjective sleep complaints could only partially predict
      abnormalities in polysomnographic (PSG) studies. CONCLUSION: In PD nocturnal
      sleep 'destructuring' is linked to disease duration and evolves independently
      from other major disease parameters.

PMID- 15946898
TI  - Complex nocturnal visual hallucinations.
AB  - BACKGROUND AND PURPOSE: To describe the clinical features and associations of
      complex nocturnal visual hallucinations. PATIENTS AND METHODS: We identified 12
      patients seen between 1997 and 2004 with complex nocturnal visual hallucinations.
      Charts were reviewed and data analyzed. RESULTS: Of the 12 patients, 11 were
      women. Vivid, silent, often distorted images of people and animals occurred after
      waking, disappearing with increased light. Idiopathic hypersomnia, beta blocker
      use, dementia with Lewy bodies, macular degeneration and anxiety were associated
      factors. The hallucinations appeared to be a primary parasomnia in four patients
      with anxiety being the only associated feature. CONCLUSIONS: Complex nocturnal
      visual hallucinations represent a well-defined syndrome with diverse causes which
      should be differentiated from other parasomnias causing arousals.

PMID- 15946899
TI  - Predictors of symptoms of anxiety and depression in obstructive sleep apnea.
AB  - BACKGROUND AND PURPOSE: To assess factors associated with anxiety and depression
      in patients with obstructive sleep apnea syndrome (OSAS). PATIENTS AND METHODS:
      The study was comprised of a postal survey with a hospital chart review.
      Questionnaires were mailed to 242 previously hospitalised patients with OSAS. We
      assessed anxiety and depression with the Hospital Anxiety and Depression scale
      (HAD). Scores on the two HAD scales (0-21 scale, higher scores represent poor
      health) were categorized as normal/borderline (< or =10), and corresponding to a
      clinical diagnosis of anxiety or depression (> or =11). In logistic regression
      analysis, we assessed the association with HAD scores > or =11, using variables
      from the chart review and self-reported data on demographics, disease history,
      smoking status, CPAP/BiPAP use, and daytime sleepiness as assessed with the
      Epworth Sleepiness Scale (ESS), as potential predictors. RESULTS: One hundred and
      seventy-eight patients (74%) with mean (SD) age 55 (11) years and body mass index
      (BMI) of 31 (5) kgm(-2) responded to the questionnaire. In multivariate logistic
      regression analysis, only low compliance with CPAP therapy (odds ratio (OR) 5.60,
      P=0.005) predicted high level of anxiety, and low compliance with CPAP therapy
      (OR 3.59, P=0.03) and daytime sleepiness (OR 1.14 per unit increase in ESS score,
      P=0.02) were the only predictors of high level of depression. CONCLUSIONS: High
      anxiety score was associated with non-compliance with CPAP therapy. High
      depression score was associated with daytime sleepiness and non-compliance with
      CPAP therapy.

PMID- 15946900
TI  - Sawtooth wave density analysis during REM sleep in temporal lobe epilepsy
      patients.
AB  - BACKGROUND AND PURPOSE: This study analyzes sawtooth waves (STW), a
      characteristic feature of rapid eye movement (REM) sleep, in temporal lobe
      epilepsy patients in order to test the hypothesis of STW dysfunction in this
      population. METHODS: Polysomnographic records from 16 patients with temporal lobe
      epilepsy and 11 controls were scored for density (STW/h of REM sleep), duration
      (STW duration in s), and frequency of STW (waves/second within each STW complex).
      These measures were compared between both groups. RESULTS: STW measures were
      significantly different in control vs. epilepsy patients; respectively, density
      was 60.8 vs. 20.9 waves/h (P<0.005), average duration was 6.5 vs. 5.4 s (P<0.005
      cycles 1-4), and frequency was 2.75 vs. 2.61 Hz (P<0.0005 across all cycles).
      CONCLUSIONS: Our measurements show a change in the density, duration and
      frequency of STW in patients with temporal lobe epilepsy compared to controls.
      Other parameters of REM sleep appear to be similar in both groups. These findings
      suggest a cortical influence on REM sleep either directly or through limbic
      hypothalamic-brainstem connections.

PMID- 15946901
TI  - Being a palliative nurse for persons with severe congestive heart failure in
      advanced homecare.
AB  - Advanced homecare for persons with congestive heart failure is a 'new' challenge
      for palliative nurses. The aim of this study is to illuminate the meaning of
      being a palliative nurse for persons with severe congestive heart failure in
      advanced homecare. Narrative interviews with 11 nurses were conducted, tape
      recorded, and transcribed verbatim. A phenomenological-hermeneutic method was
      used to interpret the text. One meaning of being a palliative nurse is being
      firmly rooted and guided by the values of palliative culture. Being adaptable to
      the patient's way of life carries great weight. On one hand nurses live out this
      value, facilitating for the patients to live their everyday life as good as
      possible. Being a facilitator is revealed as difficult, challenging, but overall
      positive. On the other hand nurses get into a tight corner when values of
      palliative culture clash and do not correspond with the nurses interpretation of
      what is good for the person with congestive heart failure. Being in such a tight
      corner is revealed as frustrating and giving rise to feelings of inadequacy.
      Thus, it seems important to reflect critical on the values of palliative culture.

PMID- 15946902
TI  - Transient siRNA-mediated attenuation of liver expression from an alpha
      galactosidase A plasmid reduces subsequent humoral immune responses to the
      transgene product in mice.
AB  - Hepatocytes are an effective depot for protein production from gene therapy
      vectors. However, when gene transfer vectors or their delivery induces hepatic
      inflammation, adaptive immune responses against the transgene product can ensue.
      In BALB/c mice, hydrodynamic delivery of a CMV-driven plasmid DNA (pDNA) bearing
      human alpha-galactosidase A (alphagal) to the liver generated antibodies against
      alphagal. This humoral immune response was more robust in a transgenic knockout
      for alphagal, the Fabry mouse. The antibody response could be attenuated in both
      mouse strains by using a promoter more restricted to hepatocytes. In an attempt
      to reduce further the humoral responses to alphagal, expression from the
      transgene was attenuated by using siRNA during the period of initial delivery
      associated liver inflammation. In both mouse models and with both promoters,
      codelivering an alphagal siRNA resulted in a 2 log decrease in initial expression
      that then increased over the next few weeks to levels generated by the pDNA
      alone. This strategy led to both attenuated antibodies and an immune status
      approximating "tolerance" to alphagal. Importantly, in the Fabry mouse, an
      alphagal siRNA together with a hepatocyte-restricted promoter gave minimal anti
      alphagal antibodies and profound tolerance, suggesting that such an approach
      might have clinical utility for genetic diseases.

PMID- 15946904
TI  - A screen of candidate genes and influence of beta2-adrenergic receptor genotypes
      in postural tachycardia syndrome.
AB  - OBJECTIVE: To screen candidate genes, encoding beta2-adrenergic receptor
      (beta2AR), alpha2C-adrenergic receptor (alpha(2C)AR), norepinephrine transporter
      (NET), and mitochondrial complex I (COI), for common single nucleotide
      polymorphisms (SNPs) in patients with postural tachycardia syndrome (POTS);
      alterations could potentially cause or aggravate orthostatic tachycardia and to
      relate beta2AR SNPs, known to effect venomotor tone, to heart rate (HR) and blood
      pressure measurements during 10-min head-up tilt. METHODS: (a) DNA extraction
      from leukocytes of 29 patients with POTS; (b) Denaturing high performance liquid
      chromatography analysis to screen for the 12-bp deletion (Del322-325) in
      alpha(2C)AR and for the alanine to proline mutation at amino acid 457 (Ala457Pro)
      in NET; (c) Systematic direct sequence analysis to screen for SNPs in beta2AR,
      NET, and COI. RESULTS: Three common polymorphisms were abundant in at least one
      allele in beta2AR resulting in a cysteine to arginine in the 5' promoter region
      (72% of patients), an arginine to glycine at amino acid-16 (Gly16; 86%), and a
      glutamine to glutamic acid at amino acid-27 (Glu27; 66%), a frequency that was no
      different to the normal Caucasian population. Orthostatic HR was significantly
      greater in patients with Glu27. Diastolic blood pressure (DBP) was significantly
      lower in a subset of patients with Gly16 whose HR were > or =120 beats/min with
      head-up tilt. All patients did not show the Ala457Pro mutation of NET; all
      sequence variants detected in alpha(2C)AR, NET, and COI were not considered
      causally related to POTS. CONCLUSIONS: Of the candidate genes screened, none
      harbored a SNP considered to be causally related to POTS. There was significant
      association of HR and DBP with SNPs of the gene encoding beta2AR; Gly16 or Glu27
      could aggravate orthostatic tachycardia by excessive venous pooling.

PMID- 15946905
TI  - Peculiarities of flor strains adapted to Sardinian sherry-like wine ageing
      conditions.
AB  - Saccharomyces cerevisiae flor yeasts, which are subjected to stressful conditions
      during wine ageing, exhibit a number of characteristics which distinguish them
      from non-flor S. cerevisiae wine strains. In the present work, 22 flor and 14 non
      flor S. cerevisiae wine strains are compared, in order to elucidate other
      possible peculiarities of these yeasts. The results obtained demonstrate that in
      contrast to the homothallic nature of the non-flor strains, 77% of the flor
      strains exhibit two variants of a semi-homothallic life cycle. Moreover, the flor
      forming ability is shown to be inversely correlated to spore viability and the
      utilisation of maltose and galactose.

PMID- 15946906
TI  - GPI-specific phospholipase D (GPI-PLD) is expressed during mouse development and
      is localized to the extracellular matrix of the developing mouse skeleton.
AB  - Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is abundant in
      serum and has a well-characterized biochemistry; however, its physiological role
      is completely unknown. Previous investigations into GPI-PLD have focused on the
      adult animal or on in vitro systems and a putative role in development has been
      neither proposed nor investigated. We describe the first evidence of GPI-PLD
      expression during mouse embryonic ossification. GPI-PLD expression was detected
      predominantly at sites of skeletal development, increasing during the course of
      gestation. GPI-PLD was observed during both intramembraneous and endochondral
      ossification and localized predominantly to the extracellular matrix of
      chondrocytes and to primary trabeculae of the skeleton. In addition, the mouse
      chondrocyte cell line ATDC5 expressed GPI-PLD after experimental induction of
      differentiation. These results implicate GPI-PLD in the process of bone formation
      during mouse embryogenesis.

PMID- 15946907
TI  - SOST is a target gene for PTH in bone.
AB  - Intermittent parathyroid hormone (PTH) application is an established
      pharmacological principle to stimulate bone formation. Yet, the molecular
      mechanisms underlying this bone anabolic action are not fully understood.
      Recently, SOST (sclerostin) was identified as a potent osteocyte expressed
      negative regulator of bone formation in vitro, in murine models and in patients
      with the bone overgrowth disorders Sclerosteosis and Van Buchem disease.
      Therefore, we have studied the impact of PTH on SOST regulation. First, we
      analyzed SOST expression during PTH-induced bone formation in a classical model
      of local bone formation. 8-month-old mice received intermittently 100 nM hPTH(1
      34) or vehicle onto the calvaria for 5 days. PTH stimulated bone formation as
      assessed by fluorochrome-marker-based histomorphometry. SOST expression was
      reduced in PTH-treated calvariae 4 h after the last administration as evaluated
      by real-time quantitative PCR. Next, we observed a decrease of SOST expression in
      femoral cortical bone of 6-month-old rats following single subcutaneous systemic
      administration of 80 microg/kg PTH(1-34). Finally, we studied SOST mRNA
      expression in bone of 11-month-old osteopenic estrogen-deprived (OVX) rats
      following 8-week systemic intermittent administration of 5 microg/kg PTH(1-34).
      PTH-treated animals displayed increases in bone mineral density as detected by
      pQCT, while SOST mRNA levels were decreased compared to vehicle-treated OVX and
      SHAM controls. PTH decreased SOST expression also in vitro. 100 nM PTH(1-34)
      inhibited expression in mouse calvaria organ cultures and in osteoblastic UMR-106
      cells within 6 h by 95%. An IC50 of 1 nM was determined for PTH(1-34) in UMR-106
      cells, whereas the PTH antagonist (d-Trp12,Tyr34)-bPTH(7-34) did not efficiently
      reduce SOST expression. Furthermore, SOST inhibition by PTH was not blocked by
      the protein synthesis inhibitor cycloheximide, indicating direct regulation, and
      PTH did not influence SOST mRNA degradation, implying transcriptional regulation.
      Finally, we observed full suppression of SOST by the cAMP inducer forskolin,
      partial inhibition by ionomycin, and no effect with PMA, indicating that PTH
      action is mainly mediated via the cAMP/PKA pathway. In summary, we have shown
      that PTH directly inhibits SOST transcription in vivo and in vitro, suggesting
      that SOST regulation may play a role in mediating PTH action in bone.

PMID- 15946903
TI  - Regulatable gene expression systems for gene therapy applications: progress and
      future challenges.
AB  - Gene therapy aims to revert diseased phenotypes by the use of both viral and
      nonviral gene delivery systems. Substantial progress has been made in making gene
      transfer vehicles more efficient, less toxic, and nonimmunogenic and in allowing
      long-term transgene expression. One of the key issues in successfully
      implementing gene therapies in the clinical setting is to be able to regulate
      gene expression very tightly and consistently as and when it is needed. The
      regulation ought to be achievable using a compound that should be nontoxic, be
      able to penetrate into the desired target tissue or organ, and have a half-life
      of a few hours (as opposed to minutes or days) so that when withdrawn or added
      (depending on the regulatable system used) gene expression can be turned "on" or
      "off" quickly and effectively. Also, the genetic switches employed should ideally
      be nonimmunogenic in the host. The ability to switch transgenes on and off would
      be of paramount importance not only when the therapy is no longer needed, but
      also in the case of the development of adverse side effects to the therapy. Many
      regulatable systems are currently under development and some, i.e., the
      tetracycline-dependent transcriptional switch, have been used successfully for in
      vivo preclinical applications. Despite this, there are no examples of switches
      that have been employed in a human clinical trial. In this review, we aim to
      highlight the main regulatable systems currently under development, the gene
      transfer systems employed for their expression, and also the preclinical models
      in which they have been used successfully. We also discuss the substantial
      challenges that still remain before these regulatable switches can be employed in
      the clinical setting.

PMID- 15946908
TI  - Intermittent administration of betalactam-antibiotics for treatment of severe
      infection in hemodialysis patients.
AB  - Infections are a leading cause of morbidity and mortality in hemodialysis
      patients. Still, due to altered pharmacokinetics and potential toxic sideeffects,
      safe and efficient antibiotic therapy in dialysis patients remains a major
      challenge. We reviewed our experience with intermittent administration of
      betalactam antibiotics for treatment of severe infections in hemodialysis
      patients. A total of 81 episodes of infection in 45 patients was assessed. All
      patients were treated with betalactam antibiotics (cefepime in 11 episodes,
      cefpirom in 33 episodes, piperacillin in 9 episodes, amoxicillin in 18 episodes,
      ceftazidime in 10 episodes, respectively). All antibiotics were given post
      hemodialysis 3x per week. Treatment was considered efficient in case of a
      significant decrease in CRP in addition to clinical response. Overall treatment
      success rate was 85% (69 episodes of infection). The decrease of CRP was 52% (6.9
      +/- 5.8 to 3.3 +/- 4.9 mg/dl; p = 0.00003). The mean duration of treatment was 19
      +/- 13 days. Treatment was generally well tolerated. We conclude, that severe
      infections in hemodialysis patients can be treated safely and efficiently with an
      empiric therapy with betalactam antibiotics. Intermittent administration,
      potentially allowing ambulatory treatment, is possible.

PMID- 15946909
TI  - Dose adjustment of ciprofloxacin in renal failure: reduce the dose or prolong the
      administration interval?
AB  - BACKGROUND: Dose adjustments of antimicrobial drugs are necessary in renal
      failure. One method of dose adjustment is to reduce the dose and the other is to
      prolong the administration interval in proportion to the reduced drug clearance.
      Pharmacokinetically, both methods involve an identical drug exposure but
      pharmacodynamically there may be differences. It is not known which dose
      adjustment method is preferable in patients with renal failure. METHODS: We
      performed simulations using a published mechanism-based pharmacokinetic/
      pharmacodynamic model of ciprofloxacin effects on growth and death of Escherichia
      coli bacteria. Ciprofloxacin 500 mg every 12 hrs was selected as the standard
      dose. In renal failure either the dose was reduced (250 mg every 12 hrs) or the
      administration interval was prolonged (500 mg every 24 hrs) in proportion to the
      reduced ciprofloxacin clearance. Simulations were done with use of a commercial
      software package. RESULTS: In normal renal function, using the standard dose,
      bacterial eradication was predicted on day 3. In renal failure, bacterial
      eradication was predicted on day 3 when using the interval prolongation scheme
      but only on day 6 when using the dose reduction scheme. The relationship between
      the efficacies of these 3 dosage schemes could have been predicted by AUC above
      MIC and AUIC, but not by AUC/MIC or time above MIC. CONCLUSION: Prolongation of
      the administration interval may be the preferable dose adjustment method in renal
      failure with ciprofloxacin. We hypothesize that these results may be transferable
      to other so-called dose-dependent antimicrobial drugs.

PMID- 15946910
TI  - Renal effects of gadopentetate dimeglumine in patients with normal and impaired
      renal function.
AB  - Gadolinium chelates are widely used in magnetic resonance imaging as contrast
      medium in patients with nephropathy. However, only few studies have investigated
      the effect of gadolinium on serum creatinine concentration and estimated GFR as
      surrogate markers of renal function. This study was performed to evaluate the
      effect of gadopentetate dimeglumine in a dose sufficient for diagnostic and
      interventional purposes on renal function in a large sample of patients. We
      analyzed serum creatinine and serum-urea levels before and after the
      administration of gadopentetate dimeglumine in patients with normal and patients
      with pre-existing impaired renal function. Age, height, body mass, sex,
      medication and preexisting illnesses such as diabetes, renal artery stenosis and
      heart disease were monitored. In 181 patients with normal renal function, there
      was no statistically significant change in serum creatinine concentration after
      the administration of gadopentetate dimeglumine (at baseline: 0.72 +/- 0.18
      mg/dl, after gadolinium: 0.73 +/- 0.22 mg/dl). In contrary, serum creatinine
      levels decreased significantly after the administration of gadolinium in 198
      patients with pre-existing renal impairment (1.82 +/- 1.03 mg/dl before and 1.72
      +/- 1.03 mg/dl after gadolinium) (p < 0.01). According to this surrogate marker
      of renal function, the change of estimated GFR in patients with normal baseline
      renal function was not significant, while in patients with impaired renal
      function, GFR increased after the administration of gadolinium (p < 0.001). The
      high diagnostic value of gadolinium contrast media is associated with a very
      small risk of adverse reactions. Our findings show that the administration of
      gadolinium even is associated with a decrease of serum creatinine in patients
      with pre-existing renal impairment. In conclusion, the use of gadolinium-based
      contrast media may be considered as a safe alternative in patients with impaired
      renal function for whom use of iodine-based contrast agents is prone to a high
      rate of radiocontrast-induced nephropathy.

PMID- 15946911
TI  - Effect of HMG-CoA-reductase inhibitors on survival in type 2 diabetes patients
      with end stage diabetic nephropathy.
AB  - INTRODUCTION: We studied the effect of HMG-CoA-reductase inhibitor (= CSE-I)
      treatment on mortality in a population of hemodialysis patients with diabetic
      nephropathy due to type 2 diabetes. Since the efficacy of CSE-I in dialysis
      patients is discussed controversially, we tested the hypothesis that only
      patients with LDL-cholesterol > 100 mg/dl benefit from CSE-I. METHODS: We
      enrolled all 445 prevalent chronic hemodialysis patients with end-stage diabetic
      nephropathy from 30 centres in Southern Germany from August 1999 to January 2000
      for prospective study until December 2003. Fasting lipid profiles prior to
      dialysis session and a complete clinical phenotype were determined at inclusion.
      We formed 2 patient groups (serum LDL > vs. < or = 100 mg/dl). Only CSE-I were
      used as lipid lowering therapy in our cohort. 122 Patients were on CSE-I therapy
      during the study. All cause mortality (ACM) was the primary end point. Survival
      analysis was performed by Kaplan Meier and multivariate Cox regression analysis.
      RESULTS: Multivariate regression analysis and Kaplan Meier survival analysis
      showed a decrease in risk for ACM for patients on CSE-I therapy, irrespective of
      lipid status (multivariate hazard ratio (= HR) 0.58; p = 0.049; ACM 72.1% (no CSE
      I) vs. 59.7% (+ CSE-I); mean survival 2.37 +/- 0.08 years (no CSE-I) vs. 2.77 +/-
      0.12 years (+ CSE-I), p = 0.003). In patients with LDL > 100 mg/dl, statin
      treatment was also associated with reduced ACM: 48.0% (+ CSE-I) vs. 70.1% (no CSE
      I), (multivariate HR 0.28, CI 95% 0.11 - 0.75, p = 0.01), but not in patients
      with LDL < or = 100 mg/dl (HR 0.84, CI 95% 0.41 - 1.72 p = 0.63). CONCLUSION: Our
      data indicates that hemodialysis patients with type 2 diabetic nephropathy may
      benefit from statin therapy irrespective of baseline LDL-cholesterol level.
      Patients with LDL > 100 mg/dl benefit most when treated with CSE-I.

PMID- 15946912
TI  - Effect of genetic variation on therapy with angiotensin converting enzyme
      inhibitors or angiotensin receptor blockers in dialysis patients.
AB  - INTRODUCTION: The role of interaction of polymorphisms in the Renin-Angiotensin
      System (RAS) with angiotensin converting enzyme (ACE) or angiotensin receptor
      (AGTR1) inhibitors (RAS inhibitors) is unknown, as is the role of such therapy in
      end stage renal disease (ESRD) patients. METHODS: We enrolled all 445 prevalent
      patients with diabetic nephropathy receiving maintenance hemodialysis in 30
      centers in Southern Germany from August 1999 to January 2000 for prospective
      survival analysis until December 2003. Blood pressure and medication was recorded
      at inclusion. We determined survival specific for allelic variants of the ACE
      (insertion/deletion), Angiotensinogen (M235T) and AGTR1 (A1166C) genes. The
      effect of therapy with RAS inhibitors at study inclusion was determined for the
      allelic variants of each gene. The primary end point was all cause mortality
      (ACM). RESULTS: For all polymorphisms, and for therapy with RAS inhibitors there
      was no significant effect on survival in the complete collective (n = 445),
      though there was an insignificant trend for improved survival in patients on
      AGTR1 antagonists. Increased ACM risk was associated with treatment with RAS
      inhibitors only in patients homozygous for the wild type AGTR1 1166A allele (HR
      1.65, p = 0.01). For all other polymorphisms, therapy with RAS inhibitors had no
      significant effect on ACM, irrespective of genotype. Similar results were
      obtained in patients with systolic ventricular dysfunction. CONCLUSION: Our data
      do not show a survival advantage for type 2 diabetes hemodialysis patients
      receiving RAS inhibiting therapy. In addition, our data indicate that allelic
      variation in RAS genes and pharmacogenetic interaction with RAS inhibition does
      not affect mortality risk in diabetic hemodialysis patients.

PMID- 15946913
TI  - Pharmacokinetics of the immunosuppressant everolimus in maintenance renal
      transplant patients.
AB  - The novel macrocyclic immunosuppressant everolimus has been approved for use in
      renal and heart transplantation. The objective of this randomized, double-blind,
      placebo-controlled, dose-escalating Phase 1 study was to evaluate the
      pharmacokinetic profile of different dosing regimens of everolimus. Fifty-four
      subjects were randomized for 4-weeks treatment with everolimus (n = 44) or
      placebo (n = 10). Steady state was reached by day 4 of multiple dosing with
      evidence for dose-proportionality over the dose range tested. Systemic
      accumulation was 1.6- to 2.2-fold with multiple dosing. Steady-state predose
      trough concentrations were well correlated with AUC (r = 0.87, p < 0.001). Within
      subject coefficients of variation for the tablet formulation ranged from 10-19%
      and between-subject coefficients from 34-60% for Cmax and AUC. There was no
      effect of common demographic parameters (age, sex, weight) on variability in
      steady-state exposure. These results support the clinical use of everolimus in
      renal transplantation.

PMID- 15946914
TI  - Problems of cyclosporine absorption profiling using C2-monitoring.
AB  - The present study sought to validate the concept of C2 monitoring in 41 de-novo
      transplant patients treated with microemulsion of cyclosporine,
      mycophenolatesodium, steroids and basiliximab. RESULTS: After 6 months patient
      and graft survival was 98%, rejection rate was 19%. In the first week only a few
      patients achieved the suggested C2 levels (19% > 1500, 50% > 1200 ng/ml) despite
      an increased cyclosporine (CsA) dose. After 14 days 63% of patients reached C2 >
      1500 ng/ml (83% C2 > 1200) despite decreased CsA dose. 35% of patients had
      intermittent high C0 (> 300) and low C2 (< 800), suggesting poor and/or slow
      absorption. Most of them suffered from CsA toxicity. There was a significant (p <
      0.05) change of absorption as measured by C2/C0 leading to an increase of
      C2/dose. CONCLUSIONS: C2 monitoring may be useful to better estimate the CsA
      exposure in individual patients; however our results indicate some limitations of
      the current concept of C2 monitoring. Despite increase of dosage many patients do
      not reach the proposed levels. A significant proportion of patients are poor
      and/or slow absorbers. CsA toxicity may not be detected by C2 monitoring alone.
      With the use of basiliximab and mycophenolatesodium lower target levels seem to
      be sufficient.

PMID- 15946915
TI  - 1-alpha-calcidol modulates major human monocyte antigens and toll-like receptors
      TLR 2 and TLR4 in vitro.
AB  - Since vitamin D derivatives are known to interfere with the cellular immune
      response, we analysed the possible effect of 1-alpha-calcidol (AC) on major
      monocyte antigens CD14 (an endotoxin receptor), HLA-DR, and toll-like recptors 2
      and 4 (TLR2, TLR4). Peripheral blood monocytes were isolated from healthy donors
      and cultured by standard protocol followed by incubation with various
      concentrations of AC in unstimulated and LPS-activated cells. After 24, 48 and 72
      hours cells were harvested and analysed for the expression of antigens by
      flowcytometry. Compared to the controls AC increased the expression of CD14 in a
      dose and time dependent manner (after 72 hours culture time p < 0.01). AC was
      capable of further stimulating CD14 expression in LPS activated monocytes (p <
      0.05). Both LPS and AC downmodulated HLA-DR dramatically after 24 (p < 0.05), 48
      (p < 0.01) and 72 hours (p < 0.0001). The expression of TLR2 but not of TLR4 was
      inhibited by 10-7M AC. The data reveal that AC significantly modulates the
      expression of CD14, HLA-DR as well as of TLR2, all involved as targets and
      effector molecules in antigen recognition and processing, relevant to overcome
      infections and organ lesions.

PMID- 15946916
TI  - Association between the promoter polymorphism T/C at position -159 of the CD14
      gene and anti-inflammatory therapy in patients with inflammatory bowel disease.
AB  - Immune response to intestinal bacteria and genetic predisposition seem to play a
      crucial role in the pathogenesis of inflammatory bowel disease. A single
      nucleotide polymorphism in the promoter of the lipopolysaccharide-receptor CD14
      gene (T/C at position -159) has recently been described. To evaluate the role of
      the CD14 gene in anti-inflammatory therapy, the functionally relevant T(-159)-->C
      promoter polymorphism has been genotyped in 72 patients with inflammatory bowel
      disease and associated with the cumulative steroid dose. Cumulative
      corticosteroid dose was significantly higher in ulcerative colitis patients with
      the TT genotype (2447.7 +/- 927.0 mg/yr) compared with the CT genotype (142.3 +/-
      142.3 mg/yr, p=0.016) and the CC genotype (391.7 +/- 272.7 mg/yr, p=0.047). In
      contrast, in patients with Crohn's disease there was no significant difference of
      the cumulative corticosteroid doses between the various T(-159)-->C promoter CD14
      genotypes. An altered immune response to lipopolysaccharides with influence on
      the anti-inflammatory therapy seems to play a role in the genetic predisposition
      to ulcerative colitis. Genetic stratification will lead to the development of
      individualized therapies in inflammatory bowel disease.

PMID- 15946917
TI  - Anatomical and physiological classification of hepatic vein dominance applied to
      liver transplantation.
AB  - BACKGROUND: Proper outflow reconstruction is essential in LDLT. Preoperative
      planning requires meticulous attention to hepatic vein dominance patterns. The
      purpose of our study was to provide a combined anatomical-physiological
      classification of hepatic vein dominance useful for surgical decision-making in
      both donors and recipients. METHODOLOGY: We analyzed 3-dimensional CT-imaging
      reconstructions of 55 potential live liver donors evaluated at our Institution
      between January 2003 and May 2004. RESULTS: Our data revealed that: 1) The middle
      hepatic vein (MHV) and left hepatic vein (LHV) show a relative lack of anatomical
      diversity, whereas the right hepatic vein (RHV) exhibits multiple variants, 2)
      45% donors had inferior hepatic veins (IHV) with anatomically and physiologically
      relevant venous drainage territories, 3) The RHV is usually dominant when present
      as a single vein without anatomical IHV (type 1A), or when considered as a
      complex with IHV (type 1Bx) (80% vs. 88%), 4) Only 55% of dominant type 1Bx
      RHV/IHV-complex automatically included a dominant type 1By RHV by itself, 5) A
      single RHV out of anatomical complex with IHV (type 1By) was dominant in only 48%
      of our donor candidates, 6) The MHV types 2A and 2By are strongly dominant
      accounting for up to 57% of total liver volume (TLV). CONCLUSIONS: We propose a
      new classification based on both anatomical and physiological hepatic venous
      configurations. Our model also provides a new nomenclature that can be
      universally applied to preoperative planning in LDLT.

PMID- 15946918
TI  - Hybrid rendering of aortic aneurysms after endoluminal stent-graft repair.

PMID- 15946919
TI  - Endothelin-1 induces CD40 but not IL-6 in human monocytes via the proinflammatory
      transcription factor NF-kappaB.
AB  - The vasoactive peptide endothelin-1 (ET-1) may contribute to the pathogenesis of
      atherosclerosis and its acute complications. Because inflammation of the vessel
      wall is a characteristic feature of atherosclerosis, this study investigated the
      effect of ET-1 on the proinflammatory transcription factor NF-kappaB in
      monocytes. Monocyte/macrophages are a major source of inflammatory mediators in
      atheroma and are located in rupture prone plaque areas. In human monocytes ET-1
      caused NF-kappaB activation. Specificity of ET-1-induced NF-kappaB activation was
      ascertained by supershift and competition experiments. This ET-1 effect was
      blocked by the ET-A-receptor antagonist BQ-123 but not by the ET-B-receptor
      antagonist BQ-788. PI-1, a specific inhibitor of the IkappaB-alpha-degrading
      proteasome complex, also prevented NF-kappaB activation. ET-1 stimulated
      expression of the proinflammatory molecule CD40 but not of the cytokine IL-6 in a
      NF-kappaB-dependent manner. CONCLUSION: The data demonstrate the ability of ET-1
      to activate inflammatory pathways in human monocytes differentially.

PMID- 15946920
TI  - Topical treatment of basal cell carcinoma with neomycin.
AB  - Basal cell carcinoma (BCC) is the most common skin cancer, occurring more
      frequently than malignancies of any other tissue or organ, either individually or
      in total. Medical treatment modalities of BCC offer cost reduction and clinical
      advantages in selected cases. Neomycin has been reported to have an important
      role on proliferation of endothelial cells and neoplastic cells. This finding may
      lead to new strategies for the therapeutic use of agents which block FGF
      activities in disease states associated with enhanced keratinocyte proliferation.
      We report here a case of BCC treated with neomycin 5% cream that induced a
      regression of BCC.

PMID- 15946921
TI  - Survival rate of endodontically treated teeth in relation to conservative vs post
      insertion techniques -- a retrospective study.
AB  - AIMS AND METHODS: The purpose of this retrospective, non-randomised cohort study
      was to evaluate the success rate of 775 endodontically treated teeth depending on
      the restoration type. A total of 508 patients with 775 endodontically treated
      teeth were examined during at least 12 months. The radiographic controls, time
      span between root canal filling and definitive restoration, restoration material
      type, inserted post system type and the occurrence of possible endodontically as
      well as restorative post-operative complications were recorded. RESULTS: 18.3% of
      the 775 investigated teeth were incisors and canines, 33.5% were premolars and
      48.2% molars. Pre-fabricated and casted metal post systems were used only in
      15.6% of the endodontically treated teeth (18.4% incisors and canines, 44.8%
      premolars, 36.8% molars). 6.6% of the teeth had endodontically related symptoms
      or severe complications, whereas in 13.2% of the teeth restored with metal posts
      showed complications, such as root or crown fractures. The Cox-Regression
      analysis showed that teeth restored with a post system had a statistically
      significant higher failure rate (p = 0.044) than those which had been restored
      without posts. CONCLUSIONS: The results showed a high success rate for
      endodontically treated teeth when the final restoration was placed within a short
      period of time (two weeks). A higher tooth loss was observed when metal post
      systems were employed suggesting that precaution is recommended when these types
      of posts are inserted.

PMID- 15946922
TI  - Th1-orientated immunological properties of the bacterial extract OM-85-BV.
AB  - The bacterial extract OM-85-BV prepared from 21 pathogenic bacterial strains is
      administered orally to adults and children for the treatment and prevention of
      recurrent infections of the respiratory tract. We analyzed in vitro and in vivo
      the immunomodulatory effects of the extract. The lysate acted as a non specific
      macrophage activator, inducing NO production as well as the translocation of
      transcription factor NF-kappaB into the nucleus in murine bone marrow-derived
      macrophages. Besides stimulating unspecifically the immune system, a bacteria
      specific humoral immune response was revealed. After oral application, a trend to
      increase bacteria-specific IgG and IgA in serum was observed. Also a marked
      increase of bacteria specific IgA in saliva as well as in supernatants of Peyer's
      patches and mesenteric lymph nodes-derived cell cultures was found. The
      immunomodulatory properties of the extract were also investigated with respect to
      shifting the Th1/Th2 bias in an in vivo allergy model. BALB/c mice were orally
      immunized with OM-85-BV and subsequently sensitized intraperitoneally with the
      allergen ovalbumin. The group pretreated with OM-85-BV showed a decrease of both
      total and ovalbumin specific IgE. Accordingly, in spleen cell supernatants the
      Th1-associated cytokine IFN-gamma was increased, and the Th2-associated cytokine
      IL-4 was downregulated. Our findings suggest that the immunoprotective effects of
      OM-85-BV observed in human beings may be correlated to its Th1 augmenting
      properties.

PMID- 15946923
TI  - Impact of intraoperative myocardial cellular damage on early hemodynamics after
      off-pump versus on-pump coronary artery bypass surgery.
AB  - BACKGROUND: Due to the surgical trauma a small amount of myocardial cellular
      damage is inherent during coronary artery bypass grafting (CABG). The purpose of
      the present study was to assess the degree of myocardial cellular damage after
      off-pump (OPCAB) and on-pump CABG (ONCAB) as measured by cardiac troponin I
      (cTnI), creatine kinase (CK), its MB isoenzyme (CK-MB) and myoglobin (Myo) and to
      examine its impact on early hemodynamics after surgery. METHODS: Ninety-nine
      consecutive OPCAB patients, operated between 01/1999 and 01/2004, were enrolled
      in the present study and compared to 99 ONCAB patients operated during the same
      period of time, who were matched for baseline data and mean number of grafts per
      patient. Early hemodynamics, cTnI, CK/CK-MB and Myo were measured preoperatively
      and at 1, 6, 12, 24 and 48 hours (h) postoperatively. Perioperative inotropic
      support, clinical data and potoperative outcome were recorded prospectively.
      RESULTS: The two groups were similar concerning preoperative characteristics. The
      mean number of distal grafts/patient was 2.1 +/- 1.0 in OPCAB and 2.1 +/- 0.8 in
      ONCAB patients (mean +/- SD). There was no significant difference among the
      groups regarding early hemodynamics in terms of cardiac index (CI), systemic
      vascular resistance index (SVRI), and left ventricular stroke work index (LVSWI),
      and inotropic support. However, cTnI, CK/CK-MB but not Myo levels were
      significantly lower in OPCAB compared to ONCAB patients at 1, 6, 12, 24, 36 and
      48 h postoperatively (P<0.05). CONCLUSIONS: Off-pump surgery results in equal
      early hemodynamics despite a significantly lower release of cTnI and CK,
      suggesting a reduced myocardial cell damage as compared to ONCAB surgery.

PMID- 15946924
TI  - When your work conditions are sicker than your patients.

PMID- 15946925
TI  - Transitional care after the intensive care unit: current trends and future
      directions.

PMID- 15946926
TI  - Predictors of complications associated with closure devices after transfemoral
      percutaneous coronary procedures.

PMID- 15946927
TI  - Alcohol withdrawal syndrome overlooked and mismanaged?

PMID- 15946928
TI  - Development and implementation of a protocol for transfers out of the pediatric
      intensive care unit.

PMID- 15946929
TI  - Our policy on external ventricular drainage systems includes the procedure for
      priming the system. Does it really have to be primed?

PMID- 15946930
TI  - How can I best protect my family from a Schiavo/Schindler situation?

PMID- 15946931
TI  - Healthy work environments: enroute to excellence.

PMID- 15946932
TI  - Making bad cells go good: the promise of epigenetic therapy.

PMID- 15946934
TI  - Gene disruption of Spred-2 causes dwarfism.
AB  - The impact of the fibroblast growth factor receptor 3 (FGFR3)-mediated signaling
      pathway on bone growth has been demonstrated by various genetic approaches.
      Overexpression of fibroblast growth factors (FGFs), several gain-of-function
      mutations in the FGFR3, and constitutive activation of mitogen-activated protein
      kinase (MAPK) kinase (MEK1) in chondrocytes have been shown to cause dwarfism in
      mice by activation of the MAPK signaling pathway. To investigate the previously
      reported inhibitory role of Spred in the FGFR3/MAPK pathway, we generated mice
      with a trapped Spred-2 gene. Here we show that lack of functional Spred-2 protein
      in mice caused a dwarf phenotype, similar to achondroplasia, the most common form
      of human dwarfism. Spred-2(-/-) mice showed reduced growth and body weight, they
      had a shorter tibia length, and showed narrower growth plates as compared with
      wild-type mice. We detected promoter activity and protein expression of Spred-2
      in chondrocytes, suggesting an important function of Spred-2 in chondrocytes and
      bone development. Stimulation of chondrocytes with different FGF concentrations
      showed earlier and augmented ERK phosphorylation in Spred-2(-/-) chondrocytes in
      comparison to Spred-2(+/+) chondrocytes. Our observations suggest a model in
      which loss of Spred-2 inhibits bone growth by inhibiting chondrocyte
      differentiation through up-regulation of the MAPK signaling pathway.

PMID- 15946935
TI  - Roles for C16-ceramide and sphingosine 1-phosphate in regulating hepatocyte
      apoptosis in response to tumor necrosis factor-alpha.
AB  - Tumor necrosis factor (TNF)-alpha signals cell death and simultaneously induces
      the generation of ceramide, which is metabolized to sphingosine and sphingosine 1
      phosphate (S1P) by ceramidase (CDase) and sphingosine kinase. Because the dynamic
      balance between the intracellular levels of ceramide and S1P (the "ceramide/S1P
      rheostat") may determine cell survival, we investigated these sphingolipid
      signaling pathways in TNF-alpha-induced apoptosis of primary hepatocytes.
      Endogenous C16-ceramide was elevated during TNF-alpha-induced apoptosis in both
      rat and mouse primary hepatocytes. The putative acid sphingomyelinase (ASMase)
      inhibitor imipramine inhibited TNF-alpha-induced apoptosis and C16-ceramide
      increase as did the knock out of ASMase. Overexpression of neutral CDase (NCDase)
      inhibited the TNF-alpha-induced increase of C16-ceramide and apoptosis in rat
      primary hepatocytes. Moreover, NCDase inhibited liver injury and hepatocyte
      apoptosis in mice treated with D-galactosamine plus TNF-alpha. This protective
      effect was abrogated by the sphingosine kinase inhibitor N,N-demethylsphingosine,
      suggesting that the survival effect of NCDase is due to not only C16-ceramide
      reduction but also S1P formation. Administration of S1P or overexpression of
      NCDase activated the pro-survival kinase AKT, and overexpression of dominant
      negative AKT blocked the survival effect of NCDase. In conclusion, activation of
      ASMase and generation of C16-ceramide contributed to TNF-alpha-induced hepatocyte
      apoptosis. NCDase prevented apoptosis both by reducing C16-ceramide and by
      activation of AKT through S1P formation. Therefore, the cross-talk between
      sphingolipids and AKT pathway may determine hepatocyte apoptosis by TNF-alpha.

PMID- 15946936
TI  - BAP31 and its caspase cleavage product regulate cell surface expression of
      tetraspanins and integrin-mediated cell survival.
AB  - BAP31, a resident integral protein of the endoplasmic reticulum membrane,
      regulates the export of other integral membrane proteins to the downstream
      secretory pathway. Here we show that cell surface expression of the tetraspanins
      CD9 and CD81 is compromised in mouse cells from which the Bap31 gene has been
      deleted. CD9 and CD81 facilitate the function of multiprotein complexes at the
      plasma membrane, including integrins. Of note, BAP31 does not appear to influence
      the egress of alpha5beta1 or alpha(v)beta3 integrins to the cell surface, but in
      Bap31-null mouse cells, these integrins are not able to maintain cellular
      adhesion to the extracellular matrix in the presence of reduced serum.
      Consequently, Bap31-null cells are sensitive to serum starvation-induced
      apoptosis. Reconstitution of wild-type BAP31 into these Bap31-null cells restores
      integrin-mediated cell attachment and cell survival after serum stress, whereas
      interference with the functions of CD9, alpha5beta1, or alpha(v)beta3 by
      antagonizing antibodies makes BAP31 cells act similar to Bap31-null cells in
      these respects. Finally, in human KB epithelial cells protected from apoptosis by
      BCL-2, the caspase-8 cleavage product, p20 BAP31, inhibits egress of tetraspanin
      and integrin-mediated cell attachment. Thus, p20 BAP31 can operate upstream of
      BCL-2 in living cells to influence cell surface properties due to its effects on
      protein egress from the endoplasmic reticulum.

PMID- 15946937
TI  - Superoxide dismutase/catalase mimetics are neuroprotective against selective
      paraquat-mediated dopaminergic neuron death in the substantial nigra:
      implications for Parkinson disease.
AB  - Exposure of mice to the herbicide paraquat has been demonstrated to result in the
      selective loss of dopaminergic neurons of the substantia nigra, pars compacta
      (SNpc) akin to what is observed in Parkinson disease (PD). In this study, we
      investigate the efficacy of two synthetic superoxide dismutase/catalase mimetics
      (EUK-134 and EUK-189) in protecting against paraquat-induced dopaminergic cell
      death in both the rat dopaminergic cell line 1RB3AN27 (N27) and primary
      mesencephalic cultures in vitro and in adult mice in vivo. Our data demonstrate
      that pretreatment with either EUK-134 or EUK-189 significantly attenuates
      paraquat-induced neurotoxicity in vitro in a concentration-dependent manner.
      Furthermore, systemic administration of EUK-189 decreases paraquat-mediated SNpc
      dopaminergic neuronal cell death in vivo. These findings support a role for
      oxidative stress in paraquat-induced neurotoxicity and suggest novel therapeutic
      approaches for neurodegenerative disorders associated with oxidative stress such
      as PD.

PMID- 15946938
TI  - BcrC from Bacillus subtilis acts as an undecaprenyl pyrophosphate phosphatase in
      bacitracin resistance.
AB  - Overexpression of the BcrC(Bs) protein, formerly called YwoA, in Escherichia coli
      or in Bacillus subtilis allows these bacteria to stand higher concentrations of
      bacitracin. It was suggested that BcrC(Bs) was a membrane-spanning domain of an
      ATP binding cassette (ABC) transporter involved in bacitracin resistance.
      However, we hypothesized that this protein has an undecaprenyl pyrophosphate
      (UPP) phosphatase activity able to compete with bacitracin for UPP. We found that
      overexpression of a recombinant His6-BcrC(Bs) protein in E. coli (i) increased
      the resistance of the cells to bacitracin and (ii) increased UPP phosphatase
      activity in membrane preparations by 600-fold. We solubilized and prepared an
      electrophoretically pure protein exhibiting a strong UPP phosphatase activity.
      BcrC(Bs), which belongs to the type 2 phosphatidic acid phosphatase (PAP2)
      phosphatase superfamily (PF01569), differs totally from the already known BacA
      UPP phosphatase from E. coli, a member of the PF02673 family of the Protein
      family (Pfam) database. Thus, BcrC(Bs) and its orthologs form a new class of
      proteins within the PAP2 phosphatase superfamily, and likely all of them share a
      UPP phosphatase activity.

PMID- 15946939
TI  - AIP4 restricts transforming growth factor-beta signaling through a ubiquitination
      independent mechanism.
AB  - Smad7 functions as an intracellular antagonist in transforming growth factor-beta
      (TGF-beta) signaling. In addition to interacting stably with the activated TGF
      beta type I receptor (TbetaRI) to prevent phosphorylation of the receptor
      regulated Smads (Smad2 and Smad3), Smad7 also induces degradation of the
      activated TbetaRI through association with different E3 ubiquitin ligases. Using
      the two-hybrid screen, we identified atrophin 1-interacting protein 4 (AIP4) as
      an E3 ubiquitin ligase that specifically targets Smad7 for ubiquitin-dependent
      degradation without affecting the turnover of the activated TbetaRI.
      Surprisingly, we found that despite the ability to degrade Smad7, AIP4 can
      inhibit TGF-beta signaling, presumably by enhancing the association of Smad7 with
      the activated TbetaRI. Consistent with this notion, expression of a catalytic
      mutant of AIP4, which is unable to induce ubiquitination and degradation of
      Smad7, also stabilizes the TbetaRI.Smad7 complex, resulting in inhibition of TGF
      beta signaling. The ability of AIP4 to enhance the inhibitory function of Smad7
      independent of its ubiquitin ligase activity reveals a new mechanism by which E3
      ubiquitin ligases may function to turn off TGF-beta signaling.

PMID- 15946940
TI  - Genetic and pharmacologic evidence that calcium-independent phospholipase A2beta
      regulates virus-induced inducible nitric-oxide synthase expression by
      macrophages.
AB  - Recent evidence supports a regulatory role for the calcium-independent
      phospholipase A2 (iPLA2) in the antiviral response of inducible nitric-oxide
      synthase (iNOS) expression by macrophages. Because two mammalian isoforms of
      iPLA2 (iPLA2beta and iPLA2gamma) have been cloned and characterized, the aim of
      this study was to identify the specific isoform(s) in macrophages that regulates
      the expression of iNOS in response to virus infection. Bromoenol lactone (BEL), a
      suicide substrate inhibitor of iPLA2, inhibits the activity of both isoforms at
      low micromolar concentrations. However, the R- and S-enantiomers of BEL display
      approximately 10-fold greater potency for inhibition of the enzymatic activity of
      iPLA2gamma and iPLA2beta, respectively. In this study, we show that the iPLA2beta
      selective (S)-BEL inhibits encephalomyocarditis virus (EMCV)-induced iNOS
      expression, nitric oxide production, and iPLA2 enzymatic activity in macrophages
      in a concentration-related manner that closely resembles the inhibitory
      properties of racemic BEL. cAMP response element-binding protein (CREB) is one
      downstream target of iPLA2 that is required for the transcriptional activation of
      iNOS in response to virus infection, and consistent with the effects of BEL
      enantiomers on iNOS expression, (S)-BEL more effectively inhibits EMCV-induced
      CREB phosphorylation than (R)-BEL in macrophages. Using macrophages isolated from
      iPLA2beta-null mice, virus infection fails to stimulate iNOS mRNA accumulation
      and protein expression, thus providing genetic evidence that iPLA2beta is
      required for EMCV-induced iNOS expression. These findings provide evidence for a
      signaling role for iPLA2beta in virus-induced iNOS expression by macrophages.

PMID- 15946941
TI  - Phosphorylation of GRK1 and GRK7 by cAMP-dependent protein kinase attenuates
      their enzymatic activities.
AB  - Phosphorylation of G protein-coupled receptors is a critical step in the rapid
      termination of G protein signaling. In rod cells of the vertebrate retina,
      phosphorylation of rhodopsin is mediated by GRK1. In cone cells, either GRK1,
      GRK7, or both, depending on the species, are speculated to initiate signal
      termination by phosphorylating the cone opsins. To compare the biochemical
      properties of GRK1 and GRK7, we measured the K(m) and V(max) of these kinases for
      ATP and rhodopsin, a model substrate. The results demonstrated that these kinases
      share similar kinetic properties. We also determined that cAMP-dependent protein
      kinase (PKA) phosphorylates GRK1 at Ser(21) and GRK7 at Ser(23) and Ser(36) in
      vitro. These sites are also phosphorylated when FLAG-tagged GRK1 and GRK7 are
      expressed in HEK-293 cells treated with forskolin to stimulate the endogenous
      production of cAMP and activation of PKA. Rod outer segments isolated from bovine
      retina phosphorylated the FLAG-tagged GRKs in the presence of dibutyryl-cAMP,
      suggesting that GRK1 and GRK7 are physiologically relevant substrates. Although
      both GRKs also contain putative phosphorylation sites for PKC and
      Ca(2+)/calmodulin-dependent protein kinase II, neither kinase phosphorylated GRK1
      or GRK7. Phosphorylation of GRK1 and GRK7 by PKA reduces the ability of GRK1 and
      GRK7 to phosphorylate rhodopsin in vitro. Since exposure to light causes a
      decrease in cAMP levels in rod cells, we propose that phosphorylation of GRK1 and
      GRK7 by PKA occurs in the dark, when cAMP levels in photoreceptor cells are
      elevated, and represents a novel mechanism for regulating the activities of these
      kinases.

PMID- 15946942
TI  - The isoprenoid substrate specificity of isoprenylcysteine
      carboxylmethyltransferase: development of novel inhibitors.
AB  - Isoprenylcysteine carboxylmethyltransferase (Icmt) is an integral membrane
      protein localized to the endoplasmic reticulum of eukaryotic cells that catalyzes
      the post-translational alpha-carboxylmethylesterification of CAAX motif proteins,
      including the oncoprotein Ras. Prior to methylation, these protein substrates all
      contain an isoprenylcysteine residue at the C terminus. In this study, we
      developed a variety of substrates and inhibitors of Icmt that vary in the
      isoprene moiety in order to gain information about the nature of the lipophilic
      substrate binding site. These isoprenoid-modified analogs of the minimal Icmt
      substrate N-acetyl-S-farnesyl-L-cysteine (AFC) were synthesized from newly and
      previously prepared farnesol analogs. Using both yeast and human Icmt enzymes,
      these compounds were found to vary widely in their ability to act as substrates,
      supporting the isoprenoid moiety as a key substrate recognition element for Icmt.
      Compound 3 is a competitive inhibitor of overexpressed yeast Icmt (K(I) = 17.1 +/
      1.7 microm). Compound 4 shows a mix of competitive and uncompetitive inhibition
      for both the yeast and the human Icmt proteins (yeast K(IC) = 35.4 +/- 3.4
      microm, K(IU) = 614.4 +/- 148 microm; human K(IC) = 119.3 +/- 18.1 microm, K(IU)
      = 377.2 +/- 42.5 microm). These data further suggest that differences in
      substrate specificity exist between the human and yeast enzymes. Biological
      studies suggest that inhibition of Icmt results in Ras mislocalization and loss
      of cellular transformation ability, making Icmt an attractive and novel
      anticancer target. Further elaboration of the lead compounds synthesized and
      assayed here may lead to clinically useful higher potency inhibitors.

PMID- 15946943
TI  - The role and mechanism of diacylglycerol-protein kinase C1 signaling in
      melanogenesis by Cryptococcus neoformans.
AB  - The fungus Cryptococcus neoformans is an opportunistic human pathogen that causes
      a life-threatening meningoencephalitis by expression of virulence factors such as
      melanin, a black pigment produced by the cell wall-associated enzyme laccase. In
      previous studies (Heung, L. J., Luberto, C., Plowden, A., Hannun, Y. A., and Del
      Poeta, M. (2004) J. Biol. Chem. 279, 21144-21153) we proposed that the
      sphingolipid enzyme inositol-phosphoryl ceramide synthase 1 (Ipc1) regulates
      melanin production through the generation of diacylglycerol (DAG), which was
      found to activate in vitro protein kinase C1 (Pkc1). Here, we investigated the
      molecular mechanisms by which DAG regulates Pkc1 in vivo and the effect of this
      regulation on laccase activity and melanin synthesis. To this end we deleted the
      putative DAG binding C1 domain of C. neoformans Pkc1 and found that the C1
      deletion abolished the activation of Pkc1 by DAG. Deletion of the C1 domain
      repressed laccase activity and, consequently, melanin production. Finally, we
      show that these biological effects observed in the C1 deletion mutant are
      mediated by alteration of cell wall integrity and displacement of laccase from
      the cell wall. These studies define novel molecular mechanisms addressing Pkc1
      laccase regulation by the sphingolipid pathway of C. neoformans, with important
      implications for understanding and targeting the Ipc1-Pkc1-laccase cascade as a
      regulator of virulence of this important human pathogen.

PMID- 15946944
TI  - Schlafen-1 causes a cell cycle arrest by inhibiting induction of cyclin D1.
AB  - Schlafen-1 (Slfn-1), the prototypic member of the Schlafen family of proteins,
      was described as an inducer of growth arrest in T-lymphocytes and causes a cell
      cycle arrest in NIH3T3 fibroblasts prior to the G1/S transition. How Slfn-1
      exerts its effects on the cell cycle is not currently known. We report that
      synchronized murine fibroblasts expressing Slfn-1 do not exit G1 when stimulated
      with fetal calf serum, platelet-derived growth factor BB (PDGF-BB) or epidermal
      growth factor (EGF). The induction of cyclin D1 by these stimuli was blocked in
      the presence of Slfn-1 as were all downstream cell cycle processes.
      Overexpression of cyclin D1 in growth-arrested, Slfn-1-expressing cells induced
      an increase in cell growth consistent with this protein being the biological
      target of Slfn-1. Activation of the mitogen-activated protein kinase pathway by
      EGF or phorbol 12-myristate 13-acetate was unaffected by Slfn-1 expression. PDGF
      signaling was, however, almost completely blocked. This was due to a lack of PDGF
      receptor expression in Slfn-1-expressing cells consistent with Slfn-1 blocking
      the cell cycle in G1 where PDGF receptor expression is normally down-regulated.
      Finally, overexpression of Slfn-1 inhibited the activation of the cyclin D1
      promoter. Slfn-1 therefore causes a cell cycle arrest during G1 by inhibiting
      induction of cyclin D1 by mitogens.

PMID- 15946945
TI  - Cyclin D1 is not an immediate target of beta-catenin following Apc loss in the
      intestine.
AB  - Cyclin D1 is postulated to be a target of the canonical Wnt pathway and critical
      for intestinal adenoma development. We show here that, unlike cyclin D1 reporter
      assays, endogenous cyclin D1 levels are not affected following antagonism of the
      Wnt pathway in vitro, nor is cyclin D1 immediately up-regulated following
      conditional loss of Apc in vivo. Cyclin D1 levels do, however, increase in a
      delayed manner in a small subset of cells, suggesting such up-regulation occurs
      as a secondary event. We also analyzed the immediate consequences of Apc loss in
      a cyclin D1(-/-) background and failed to find any cyclin D1-dependent
      phenotypes. However, we did observe elevated cyclin D1 expression in lesions
      developing 20 days after Apc loss. In these circumstances, all adenomas (but not
      smaller lesions) showed cyclin D1 up-regulation. Finally in a smaller study, we
      analyzed whether cyclin D1 deficiency affected adenoma formation 20 days
      following induced loss of Apc. Unlike AhCre(+) Apc(fl/fl) mice (which all
      developed adenomas), doubly mutant AhCre(+) Apc(fl/fl) cyclin D1(-/-) mice only
      developed small lesions. Taken together, this argues that cyclin D1 up-regulation
      in intestinal neoplasia is important for tumor progression rather than
      initiation.

PMID- 15946946
TI  - Changes in ribosomal binding activity of eIF3 correlate with increased
      translation rates during activation of T lymphocytes.
AB  - The rate of protein synthesis in quiescent peripheral blood T lymphocytes
      increases dramatically following mitogenic activation. The stimulation of
      translation is due to an increase in the rate of initiation caused by the
      regulation of initiation factor activities. Here, we focus on eIF3, a large
      multiprotein complex that plays a central role in the formation of the 40 S
      initiation complex. Using sucrose density gradient centrifugation to analyze
      ribosome complexes, we find that most eIF3 is not bound to 40 S ribosomal
      subunits in unactivated T lymphocytes but becomes ribosome-bound following
      activation. Immunoblot analyses of sucrose gradient fractions for individual eIF3
      subunits show that the small eIF3j subunit is unassociated with the eIF3 complex
      in quiescent T lymphocytes, but upon activation joins the other eIF3 subunits and
      binds 40 S ribosomal subunits. Because eIF3j has been shown to be required for
      eIF3 binding to 40 S ribosomes in vitro, the results suggest that mitogenic
      stimulation of T lymphocytes leads to an activation of eIF3j, thereby enabling
      eIF3 to bind to the larger ribosome-free eIF3 subunit complex, and then to the 40
      S ribosomes. The association of eIF3j with the other eIF3 subunits appears to be
      inhibited by rapamycin, suggesting a mechanism that lies downstream from the
      mammalian target of rapamycin kinase. This association requires ionomycin
      together with a phorbol ester, which also suggests that calcium signaling is
      involved. We conclude that the complex formation of eIF3 and its association with
      the ribosomes might contribute to increased translation rates during T lymphocyte
      activation.

PMID- 15946947
TI  - The CXCR1 and CXCR2 receptors form constitutive homo- and heterodimers
      selectively and with equal apparent affinities.
AB  - Both homo- and heterodimeric interactions between the CXCR1 and CXCR2 chemokine
      receptors were observed following co-expression of forms of these receptors in
      HEK293 cells using assays, including co-immunoprecipitation, single cell imaging
      of fluorescence resonance energy transfer, cell surface time-resolved
      fluorescence resonance energy transfer, and bioluminescence resonance energy
      transfer. These interactions were constitutive and unaffected by the presence of
      the agonist interleukin 8 and selective as no significant interactions were noted
      between either the CXCR1 or CXCR2 receptor and the alpha(1A)-adrenoreceptor.
      Saturation bioluminescence resonance energy transfer indicated that heteromeric
      interactions between CXCR1 and CXCR2 were of similar affinity as the
      corresponding homomeric interactions. A novel endoplasmic reticulum trapping
      strategy demonstrated that these interactions were initiated during protein
      synthesis and maturation and prior to cell surface delivery. These studies
      indicated that CXCR1-CXCR2 heterodimers are as likely to form in cells co
      expressing these two chemokine receptors as the corresponding homodimers and
      stand in contrast to previous studies indicating an inability of the CXCR1
      receptor to homodimerize or to interact with the CXCR2 receptor (Trettel, F., Di
      Bartolomeo, S., Lauro, C., Catalano, M., Ciotti, M. T., and Limatola, C. (2003)
      J. Biol. Chem. 278, 40980-40988).

PMID- 15946948
TI  - Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy
      subunit mRNA stability by oxidative stress involving p38 mitogen-activated
      protein kinase signaling.
AB  - Expression of the gamma-glutamylcysteine synthetase heavy subunit (gamma-GCSh),
      which encodes the rate-limiting enzymes for glutathione biosynthesis, is
      regulated by many cytotoxic agents. Moreover, gamma-GCSh mRNA expression is
      elevated in colorectal cancer, but how gamma-GCSh expression is regulated is not
      completely understood. By using actinomycin D, which inhibits new RNA synthesis,
      we showed that treatment of human colorectal cancer cells with the prooxidant
      sulindac increased the half-life of gamma-GCSh mRNA. By using a tetracycline
      regulated gamma-GCSh mRNA assay system, we systematically dissected the cis
      acting sequence and trans-acting factors that regulate the stability of gamma
      GCSh by cytotoxic prooxidants. We demonstrated that a HuR recognition sequence,
      AUUUA, in the 3'-untranslated region is responsible for the decay of gamma-GCSh
      mRNA. Oxidative stress enhanced cytoplasmic content of HuR. Overexpression of HuR
      by transfection stabilized gamma-GCSh mRNA, whereas overexpression of a dominant
      negative HuR mutant suppressed the induced stability. Furthermore, prooxidant
      induced gamma-GCSh mRNA stabilization and HuR binding were blocked by p38 mitogen
      activated protein kinase inhibitors. We provide the first evidence that reduction
      oxidation regulation of gamma-GCSh expression, itself a reduction-oxidation
      sensor and regulator, is mediated at least in part by the p38 mitogen-activated
      protein kinase signaling through the HuR RNA-binding protein.

PMID- 15946949
TI  - Progressive accumulation of mitochondrial DNA mutations and decline in
      mitochondrial function lead to beta-cell failure.
AB  - A key adaptation enabling the fetus to survive in a limited energy environment
      may be the reprogramming of mitochondrial function, which can have deleterious
      effects. Critical questions are whether mitochondrial dysfunction progressively
      declines after birth, and if so, what mechanism might underlie this process. To
      address this, we developed a model of intrauterine growth retardation (IUGR) in
      the rat that leads to diabetes in adulthood. Reactive oxygen species (ROS)
      production and oxidative stress gradually increased in IUGR islets. ATP
      production was impaired and continued to deteriorate with age. The activities of
      complex I and III of the electron transport chain progressively declined in IUGR
      islets. Mitochondrial DNA point mutations accumulated with age and were
      associated with decreased mitochondrial DNA content and reduced expression of
      mitochondria-encoded genes in IUGR islets. Mitochondrial dysfunction resulted in
      impaired insulin secretion. These results demonstrate that IUGR induces
      mitochondrial dysfunction in the fetal beta-cell, leading to increased production
      of ROS, which in turn damage mitochondrial DNA. A self-reinforcing cycle of
      progressive deterioration in mitochondrial function leads to a corresponding
      decline in beta-cell function. Finally, a threshold in mitochondrial dysfunction
      and ROS production is reached, and diabetes ensues.

PMID- 15946950
TI  - Immortalized mouse mammary fibroblasts lacking dioxin receptor have impaired
      tumorigenicity in a subcutaneous mouse xenograft model.
AB  - Although the dioxin receptor, the aryl hydrocarbon receptor (AhR), is considered
      a major regulator of xenobiotic-induced carcinogenesis, its role in tumor
      formation in the absence of xenobiotics is still largely unknown. Trying to
      address this question, we have produced immortalized cell lines from wild-type (T
      FGM-AhR+/+) and mutant (T-FGM-AhR-/-) mouse mammary fibroblasts by stable co
      transfection with the simian virus 40 (SV-40) large T antigen and proto-oncogenic
      c-H-Ras. Both cell lines had a myofibroblast phenotype and similar proliferation,
      doubling time, SV-40 and c-H-Ras expression and activity, and cell cycle
      distribution. AhR+/+ and AhR-/- cells were also equally able to support growth
      factor- and anchorage-independent proliferation. However, the ability of T-FGM
      AhR-/- to induce subcutaneous tumors (leimyosarcomas) in NOD/SCID-immunodeficient
      mice was close to 4-fold lower than T-FGM-AhR+/+. In culture, T-FGM-AhR-/- had
      diminished migration in collagen-I and decreased lamellipodia formation. VEGFR
      1/Flt-1, a VEGF receptor that regulates cell migration and blood vessel
      formation, was also down-regulated in AhR-/- cells. Signaling through the ERK-FAK
      PKB/AKT-Rac-1 pathway, which contributes to cell motility and invasion, was also
      significantly inhibited in T-FGM-AhR-/-. Thus, the lower tumorigenic potential of
      T-FGM-AhR-/- could result from a compromised adaptability of these cells to the
      in vivo microenvironment, possibly because of an impaired ability to migrate and
      to respond to angiogenesis.

PMID- 15946951
TI  - Crystal structure of isoaspartyl aminopeptidase in complex with L-aspartate.
AB  - The crystal structure of Escherichia coli isoaspartyl aminopeptidase/asparaginase
      (EcAIII), an enzyme belonging to the N-terminal nucleophile (Ntn)-hydrolases
      family, has been determined at 1.9-A resolution for a complex obtained by
      cocrystallization with l-aspartate, which is a product of both enzymatic
      reactions catalyzed by EcAIII. The enzyme is a dimer of heterodimers,
      (alphabeta)(2). The (alphabeta) heterodimer, which arises by autoproteolytic
      cleavage of the immature protein, exhibits an alphabetabetaalpha-sandwich fold,
      typical for Ntn-hydrolases. The asymmetric unit contains one copy of the
      EcAIII.Asp complex, with clearly visible l-aspartate ligands, one bound in each
      of the two active sites of the enzyme. The l-aspartate ligand is located near
      Thr(179), the N-terminal residue of subunit beta liberated in the autoproteolytic
      event. Structural comparisons with the free form of EcAIII reveal that there are
      no major rearrangements of the active site upon aspartate binding. Although the
      ligand binding mode is similar to that observed in an l-aspartate complex of the
      related enzyme human aspartylglucosaminidase, the architecture of the EcAIII
      active site sheds light on the question of substrate specificity and explains why
      EcAIII is not able to hydrolyze glycosylated asparagine substrates.

PMID- 15946952
TI  - Cell surface expression of CD147/EMMPRIN is regulated by cyclophilin 60.
AB  - CD147, also known as extracellular matrix metalloproteinase inducer, is a
      regulator of matrix metalloproteinase production and also serves as a signaling
      receptor for extracellular cyclophilins. Previously, we demonstrated that cell
      surface expression of CD147 is sensitive to cyclophilin-binding drug cyclosporin
      A, suggesting involvement of a cyclophilin in the regulation of intracellular
      transport of CD147. In this report, we identify this cyclophilin as cyclophilin
      60 (Cyp60), a distinct member of the cyclophilin family of proteins. CD147 co
      immunoprecipitated with Cyp60, and confocal immunofluorescent microscopy revealed
      intracellular co-localization of Cyp60 and CD147. This interaction with Cyp60
      involved proline 211 of CD147, which was shown previously to be critical for
      interaction between CD147 and another cyclophilin, cyclophilin A, in solution.
      Mutation of this proline residue abrogated co-immunoprecipitation of CD147 and
      Cyp60 and reduced surface expression of CD147 on the plasma membrane. Suppression
      of Cyp60 expression using RNA interference had an effect similar to that of
      cyclosporin A: reduction of cell surface expression of CD147. These results
      suggest that Cyp60 plays an important role in the translocation of CD147 to the
      cell surface. Therefore, Cyp60 may present a novel target for therapeutic
      interventions in diseases where CD147 functions as a pathogenic factor, such as
      cancer, human immunodeficiency virus infection, or rheumatoid arthritis.

PMID- 15946953
TI  - Heberkinasa: recombinant streptokinase.

PMID- 15946954
TI  - Critical role of bare-metal stent controls in trials of drug-eluting stents.

PMID- 15946955
TI  - Limitations of the study evaluating fibrinolytic therapy and in-hospital PCI for
      ST-elevation myocardial infarction.

PMID- 15946956
TI  - Safe, sensible, sagacious: responsible scanning of pacemaker patients.

PMID- 15946957
TI  - Outcome of pregnancy in patients after repair of aortic coarctation.
AB  - AIMS: Nowadays, most women born with aortic coarctation reach childbearing age.
      However, data on outcome of pregnancy in women after repair of aortic coarctation
      are scarce. The aim of this study was to report on maternal and neonatal outcome
      of pregnancy in women after aortic coarctation repair. METHODS AND RESULTS: The
      CONCOR national registry on congenital heart disease in The Netherlands was
      reviewed for women of childbearing age (> or =18 years old) with a history of
      aortic coarctation repair. Medical history and maternal, obstetrical, and
      neonatal outcome were determined. Fifty-four of the 100 women included had a
      history of pregnancy. The 54 women had 126 pregnancies resulting in 98 successful
      pregnancies, 22 miscarriages, and six abortions. The success rate was estimated
      as 0.778 (SE 0.002) including abortions and 0.817 (SE 0.002) excluding abortions.
      There were 85 vaginal deliveries, seven vaginal deliveries with epidural
      analgesia, and six caesarean sections. There were two neonatal deaths. A total of
      26 pregnancies were complicated by a hypertensive disorder of pregnancy. There
      were 21 pregnancies in 14 women complicated by hypertension and five pregnancies
      in four women complicated by pre-eclampsia. The hypertension- and pre-eclampsia
      probabilities were estimated as 0.183 (SE 0.285) and 0.061 (SE 0.211),
      respectively. During pregnancy, five patients had an increase > or =15 mmHg
      across the site of repair at echocardiography, but only one patient required
      reintervention for recoarctation after delivery. Four of the 98 children (4%) had
      a congenital heart defect. CONCLUSION: Pregnancy is well tolerated in women after
      repair of aortic coarctation. However, an excess of miscarriages and hypertensive
      disorders of pregnancy were found.

PMID- 15946958
TI  - Psychological distress and cardiovascular disease: results from the 2002 National
      Health Interview Survey.
AB  - AIMS: The objective of this study was to examine the burden of psychological
      distress among individuals with different forms of heart disease in a large
      representative sample of adults. METHODS AND RESULTS: Data were obtained from the
      2002 National Health Interview Survey, which is a large annual survey of the US
      non-institutionalized civilian population. Psychological distress was assessed
      with a standardized questionnaire (K6) and heart disease diagnoses were based on
      self-report. Among non-diseased individuals, the estimated prevalence of
      psychological distress was 2.8%, whereas the estimates were 10, 6.4, and 4.1%
      among those with congestive heart failure (CHF), myocardial infarction (MI), and
      coronary heart disease (CHD), respectively. Over 1 million individuals with one
      or more of these conditions are estimated to experience psychological distress.
      However, only 31-35% of the participants with heart disease and psychological
      distress have visited a mental health professional. The logistic regression model
      results indicate that MI (OR 2.0, 95% CI 1.4-3.0) and CHF (OR 3.1, 95% CI 1.8
      5.1) are significantly associated with psychological distress. CONCLUSION: These
      findings imply that psychological distress is a significant comorbidity of
      cardiovascular disease. Other investigations have demonstrated a link between
      psychological distress and morbidity and mortality. Taken together, these
      findings provide the impetus for future investigations that assess the role that
      a medical and mental health care professional intervention may have in altering
      these outcomes when targeted at this distress.

PMID- 15946959
TI  - Representation of facial muscles in human motor cortex.
AB  - Whether there is a projection from the primary motor cortex (M1) to upper facial
      muscles and how the facial M1 area is modulated by intracortical inhibitory and
      facilitatory circuits remains controversial. To assess these issues, we applied
      transcranial magnetic stimulation (TMS) to the M1 and recorded from resting and
      active contralateral (C-OOc) and ipsilateral orbicularis oculi (I-OOc), and
      contralateral (C-Tr) and ipsilateral triangularis (I-Tr) muscles in 12
      volunteers. In five subjects, the effects of stimulating at different scalp
      positions were assessed. Paired TMS at interstimulus intervals (ISIs) of 2 ms
      were used to elicit short interval intracortical inhibition (SICI) and ISI of 10
      ms for intracortical facilitation (ICF). Long interval intracortical inhibition
      (LICI) was evaluated at ISIs between 50 and 200 ms, both at rest and during
      muscle activation. The silent period (SP) was also determined. C-OOc and I-OOc
      responses were recorded in all subjects. The optimal position for eliciting C-OOc
      responses was lateral to the hand representation in all subjects and MEP
      amplitude markedly diminished when the coil was placed 2 cm away from the optimal
      position. For the I-OOc, responses were present in more scalp sites and the
      latency decreased with more anterior placement of the coil. C-Tr response was
      recorded in 10 out of 12 subjects and the I-Tr muscle showed either no response
      or low amplitude response, probably due to volume conduction. SICI and ICF were
      present in the C-OOc and C-Tr, but not in the I-OOc muscle. Muscle activation
      attenuated SICI and ICF. LICI at rest showed facilitation at 50 ms ISI in all
      muscles, but there was no significant inhibition at other ISIs. There was no
      significant inhibition or facilitation with the LICI protocol during muscle
      contraction. The SP was present in the C-OOc, C-Tr and I-OOc muscles and the mean
      durations ranged from 92 to 104 ms. These findings suggest that the I-OOc muscle
      response is probably related to the first component (R1) of the blink reflex.
      There is M1 projection to the contralateral upper and lower facial muscles in
      humans and the facial M1 area is susceptible to cortical inhibition and
      facilitation, similar to limb muscles.

PMID- 15946960
TI  - Migration of human melanoma cells depends on extracellular pH and Na+/H+
      exchange.
AB  - Their glycolytic metabolism imposes an increased acid load upon tumour cells. The
      surplus protons are extruded by the Na+/H+ exchanger (NHE) which causes an
      extracellular acidification. It is not yet known by what mechanism extracellular
      pH (pHe) and NHE activity affect tumour cell migration and thus metastasis. We
      studied the impact of pHe and NHE activity on the motility of human melanoma
      (MV3) cells. Cells were seeded on/in collagen I matrices. Migration was monitored
      employing time lapse video microscopy and then quantified as the movement of the
      cell centre. Intracellular pH (pHi) was measured fluorometrically. Cell-matrix
      interactions were tested in cell adhesion assays and by the displacement of
      microbeads inside a collagen matrix. Migration depended on the integrin
      alpha2beta1. Cells reached their maximum motility at pHe approximately 7.0. They
      hardly migrated at pHe 6.6 or 7.5, when NHE was inhibited, or when NHE activity
      was stimulated by loading cells with propionic acid. These procedures also caused
      characteristic changes in cell morphology and pHi. The changes in pHi, however,
      did not account for the changes in morphology and migratory behaviour. Migration
      and morphology more likely correlate with the strength of cell-matrix
      interactions. Adhesion was the strongest at pHe 6.6. It weakened at basic pHe,
      upon NHE inhibition, or upon blockage of the integrin alpha2beta1. We propose
      that pHe and NHE activity affect migration of human melanoma cells by modulating
      cell-matrix interactions. Migration is hindered when the interaction is too
      strong (acidic pHe) or too weak (alkaline pHe or NHE inhibition).

PMID- 15946961
TI  - Hemicerebellectomy blocks the enhancement of cortical motor output associated
      with repetitive somatosensory stimulation in the rat.
AB  - Repetitive peripheral stimulation is associated with an enhancement of the
      intensity of corticomotor responses. We analysed the effects of
      hemicerebellectomy on the modulation of cortical motor output associated with
      repetitive electrical stimulation of the sciatic nerve in the rat.
      Hemicerebellectomy blocked the enhancement of the corticomotor response. The
      cerebellum is a key player in this form of short-term plasticity.

PMID- 15946962
TI  - Confocal imaging of [Ca2+] in cellular organelles by SEER, shifted excitation and
      emission ratioing of fluorescence.
AB  - Intracellular calcium signals regulate multiple cellular functions. They depend
      on release of Ca2+ from cellular stores into the cytosol, a process that appears
      to be tightly controlled by changes in [Ca2+] within the store. A method to image
      free [Ca2+] within cellular organelles was devised, which provided the first
      quantitative confocal images of [Ca2+] inside the sarcoplasmic reticulum (SR) of
      skeletal muscle. The method exploits, for greater sensitivity, the dual spectral
      shifts that some fluorescent dyes undergo upon binding Ca2+. It was implemented
      with mag-indo-1 trapped in the intracellular organelles of frog skeletal muscle
      and validated showing that it largely monitors [Ca2+] in a caffeine-sensitive
      compartment with the structure of the SR cisternae. A tentative calibration in
      situ demonstrated an increase in the dye's dissociation constant, not unlike that
      observed for other dyes in cellular environments. This increase, together with
      other characteristics of the ratioing method, placed the half-signal [Ca2+] near
      1 mM, a value suitable for cellular stores. Demonstrated advantages of the
      technique include accuracy (that of a calibrated ratiometric method), dynamic
      range and sensitivity (from the combination of two spectral shifts), spatial and
      temporal resolution, and compatibility with a vast array of visible dyes to
      monitor diverse aspects of cellular function. SEER (shifted excitation and
      emission ratioing) also provides a [Ca2+]-independent measure of dye
      concentration in the cell. Store and mitochondrial [Ca2+] ([Ca2+]SR and
      [Ca2+]mito could be measured separately using the high spatial resolution of
      SEER. Evolution of [Ca2+]SR was followed upon changes in cytosolic [Ca2+]
      ([Ca2+]cyto). At [Ca2+]cyto = 100 nM, [Ca2+]mito remained near the lower limit of
      detection and [Ca2+]SR stabilized at values that were submillimolar according to
      our tentative calibration. Steady [Ca2+]SR was only slightly higher in 800 nM
      [Ca2+]cyto, and essentially did not decrease unless [Ca2+]cyto was reduced below
      10 nM. While the increase of [Ca2+]SR was limited by loss through Ca2+ release
      channels, its decrease in low [Ca2+]cyto was largely dependent on leaks through
      the SR Ca2+ pump.

PMID- 15946963
TI  - Maximal force, voluntary activation and muscle soreness after eccentric damage to
      human elbow flexor muscles.
AB  - Muscle damage reduces voluntary force after eccentric exercise but impaired
      neural drive to the muscle may also contribute. To determine whether the delayed
      onset muscle soreness, which develops approximately 1 day after exercise, reduces
      voluntary activation and to identify the possible site for any reduction,
      voluntary activation of elbow flexor muscles was examined with both motor cortex
      and motor nerve stimulation. We measured maximal voluntary isometric torque
      (MVC), twitch torque, muscle soreness and voluntary activation in eight subjects
      before, immediately after, 2 h after, 1, 2, 4 and 8 days after eccentric
      exercise. Motor nerve stimulation and motor cortex stimulation were used to
      derive twitch torques and measures of voluntary activation. Eccentric exercise
      immediately reduced the MVC by 38 +/- 3% (mean +/- s.d., n = 8). The resting
      twitch produced by motor nerve stimulation fell by 82 +/- 6%, and the estimated
      resting twitch by cortical stimulation fell by 47 +/- 15%. While voluntary torque
      recovered after 8 days, both measures of the resting twitch remained depressed.
      Muscle tenderness occurred 1-2 days after exercise, and pain during contractions
      on days 1-4, but changes in voluntary activation did not follow this time course.
      Voluntary activation assessed with nerve stimulation fell 19 +/- 6% immediately
      after exercise but was not different from control values after 2 days. Voluntary
      activation assessed by motor cortex stimulation was unchanged by eccentric
      exercise. During MVCs, absolute increments in torque evoked by nerve and cortical
      stimulation behaved differently. Those to cortical stimulation decreased whereas
      those to nerve stimulation tended to increase. These findings suggest that
      reduced voluntary activation contributes to the early force loss after eccentric
      exercise, but that it is not due to muscle soreness. The impairment of voluntary
      activation to nerve stimulation but not motor cortical stimulation suggests that
      the activation deficit lies in the motor cortex or at a spinal level.

PMID- 15946964
TI  - Impaired modulation of sympathetic alpha-adrenergic vasoconstriction in
      contracting forearm muscle of ageing men.
AB  - Recent evidence indicates that older healthy humans demonstrate greater
      vasoconstrictor tone in their active muscles during exercise compared with young
      adults. Therefore, we tested the hypothesis that the normal ability of muscle
      contractions to blunt sympathetic alpha-adrenergic vasoconstriction (functional
      sympatholysis) is impaired with age in healthy humans. We measured forearm blood
      flow (FBF; Doppler ultrasound) and calculated the forearm vascular conductance
      (FVC) responses to alpha-adrenergic receptor stimulation during rhythmic handgrip
      exercise (15% maximum voluntary contraction) and during a control non-exercise
      vasodilator condition (intra-arterial adenosine infusion) in seven young (25 +/-
      2 years) and eight healthy older men (65 +/- 2 year). FVC responses to intra
      arterial tyramine (evokes endogenous noradrenaline release), phenylephrine
      (alpha1-agonist) and clonidine (alpha2-agonist) were assessed. In young men, the
      vasoconstrictor responses to tyramine (-25 +/- 1 versus -56 +/- 6%),
      phenylephrine (-11 +/- 4 versus -39 +/- 4%) and clonidine (-12 +/- 4 versus -38
      +/- 5%; all P < 0.005) were blunted during exercise compared with adenosine. In
      contrast, exercise did not significantly blunt the response to tyramine (-30 +/-
      2 versus -36 +/- 7%; P = 0.4) or phenylephrine (-16 +/- 2 versus -19 +/- 3%; P =
      0.3) in older men, but did attenuate the response to clonidine (-22 +/- 3 versus 
      37 +/- 6%; P < 0.05). The magnitude of functional sympatholysis, calculated as
      the difference in the vasoconstrictor responses during adenosine infusion and
      exercise, was significantly lower in older compared with young men in the
      presence of tyramine (-6 +/- 7 versus -31 +/- 6%), phenylephrine (-3 +/- 3 versus
      -28 +/- 4%) and clonidine (-15 +/- 4 versus -26 +/- 3%; all P < 0.05). We
      conclude that ageing is associated with impaired functional sympatholysis in the
      vascular beds of contracting forearm muscle in healthy men. These findings might
      help explain the greater skeletal muscle vasoconstrictor tone and reduced blood
      flow during large muscle dynamic exercise in older adults.

PMID- 15946965
TI  - Modulation of potassium currents by angiotensin and oxidative stress in cardiac
      cells from the diabetic rat.
AB  - Diabetes induces oxidative stress and leads to attenuation of cardiac K+
      currents. We investigated the role of superoxide ions and angiotensin II (ANG II)
      in generating and linking oxidative stress to the modulation of K+ currents under
      diabetic conditions. K+ currents were measured using patch-clamp methods in
      ventricular myocytes from streptozotocin (STZ)-induced diabetic rats. Superoxide
      ion levels, indicating oxidative stress, were measured by fluorescent labelling
      with dihydroethidium (DHE). ANG II content was measured using enzyme-linked
      immunosorbent asssay (ELISA). The results showed DHE fluorescence to be
      significantly higher in cells from diabetic males, compared to controls. Relief
      of stress by the NADPH oxidase inhibitor apocynin or by superoxide dismutase
      (SOD) but not by catalase reversed the attenuation of K+ currents and reduced DHE
      fluorescence. In cells from diabetic females, neither apocynin nor SOD augmented
      K+ currents, ANG II was not elevated and DHE fluorescence was significantly
      weaker than in cells from males. Reduced glutathione (GSH) also augmented K+
      currents in cells from diabetic males but not females. In ovariectomized diabetic
      females K+ currents were augmented by GSH and apocynin. Current augmentation and
      the attenuation of DHE fluorescence by apocynin were significantly blunted by
      excess ANG II (300 nm). Diabetic male rats pretreated with the angiotensin
      converting enzyme (ACE) inhibitor quinapril were hyperglycaemic, but their
      cellular ANG II levels and DHE fluorescence were significantly decreased. In
      cells from these rats, K+ currents were insensitive to apocynin. In conclusion,
      diabetes-related oxidative stress attenuates K+ currents through ANG II-generated
      increased superoxide ion levels. When ANG II levels are lower, as in diabetic
      females or following ACE inhibition in males, oxidative stress is reduced, with
      blunted alterations in K+ currents.

PMID- 15946966
TI  - Phenylephrine acts via IP3-dependent intracellular NO release to stimulate L-type
      Ca2+ current in cat atrial myocytes.
AB  - This study determined the effects of alpha1-adrenergic receptor (alpha1-AR)
      stimulation by phenylephrine (PE) on L-type Ca2+ current (I(Ca,L)) in cat atrial
      myocytes. PE (10 microm) reversibly increased I(Ca,L) (51.3%; n = 40) and shifted
      peak I(Ca,L) activation voltage by -10 mV. PE-induced stimulation of I(Ca,L) was
      blocked by each of 1 microm prazocin, 10 microm L-NIO, 10 microm W-7, 10 microm
      ODQ, 2 microm H-89 or 10 microm LY294002, and was unaffected by 10 microm
      chelerythrine or incubating cells in pertussis toxin (PTX). PE-induced
      stimulation of I(Ca,L) also was inhibited by each of 10 microm ryanodine or 5
      microm thapsigargin, by blocking IP3 receptors with 2 microm 2-APB or 10 microm
      xestospongin C or by intracellular dialysis of heparin. In field-stimulated
      cells, PE increased intracellular NO (NOi) production. PE-induced NOi release was
      inhibited by each of 1 microm prazocin, 10 microm L-NIO, 10 microm W-7, 10 microm
      LY294002, 2 microm H-89, 10 microm ryanodine, 5 microm thapsigargin, 2 microm 2
      APB or 10 microm xestospongin C, and unchanged by PTX. PE (10 microm) increased
      phosphorylation of Akt, which was inhibited by LY294002. Confocal microscopy
      showed that PE stimulated NOi release from subsarcolemmal sites and this was
      prevented by 2 mm methyl-beta-cyclodextrin, an agent that disrupts caveolae
      formation. PE also increased local, subsarcolemmal SR Ca2+ release via IP3
      dependent signalling. Electron micrographs of atrial myocytes show peripheral SR
      cisternae in close proximity to clusters of caveolae. We conclude that in cat
      atrial myocytes PE acts via alpha1-ARs coupled to PTX-insensitive G-protein to
      release NOi, which in turn stimulates I(Ca,L). PE-induced NOi release requires
      stimulation of both PI-3K/Akt and IP3-dependent Ca2+ signalling. NO stimulates
      I(Ca,L) via cGMP-mediated cAMP-dependent PKA signalling. IP3-dependent Ca2+
      signalling may enhance local SR Ca2+ release required to activate Ca2+-dependent
      eNOS/NOi production from subsarcolemmal caveolae sites.

PMID- 15946967
TI  - Differential chemosensory function and receptor expression of splanchnic and
      pelvic colonic afferents in mice.
AB  - Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different
      mechanosensory information from the colon to the spinal cord. Here we determined
      whether these pathways also differ in their chemosensitivity and receptor
      expression. Using an in vitro mouse colon preparation, individual primary
      afferents were tested with selective P2X and transient receptor potential
      vanilloid receptor 1 (TRPV1) receptor ligands. Afferent cell bodies in
      thoracolumbar and lumbosacral dorsal root ganglia (DRG) were retrogradely
      labelled from the colon and analysed for P2X3- and TRPV1-like immunoreactivity
      (LI). Forty per cent of LSN afferents responded to alpha,beta-methylene adenosine
      5'-triphosphate (alpha,beta-meATP; 1 mm), an effect that was concentration
      dependent and reversed by the P2X antagonist pyridoxyl5-phosphate 6-azophenyl
      2',4'-disulphonic acid (PPADS) (100 microm). Significantly fewer PN afferents
      (7%) responded to alpha,beta-meATP. Correspondingly, 36% of colonic thoracolumbar
      DRG neurones exhibited P2X3-LI compared with only 19% of colonic lumbosacral
      neurones. Capsaicin (3 microm) excited 61% of LSN afferents and 47% of PN
      afferents; 82% of thoracolumbar and 50% of lumbosacral colonic DRG neurones
      displayed TRPV1-LI. Mechanically insensitive afferents were recruited by
      alpha,beta-meATP or capsaicin, and were almost exclusive to the LSN. Capsaicin
      responsive LSN afferents displayed marked mechanical desensitization after
      responding to capsaicin, which did not occur in capsaicin-responsive PN
      afferents. Therefore, colonic LSN and PN pathways differ in their
      chemosensitivity to known noxious stimuli and their corresponding receptor
      expression. As these pathways relay information that may relate to symptoms in
      functional gastrointestinal disease, these results may have implications for the
      efficacy of therapies targeting receptor modulation.

PMID- 15946969
TI  - Profound regulation of neonatal CA1 rat hippocampal GABAergic transmission by
      functionally distinct kainate receptor populations.
AB  - Neonatal hippocampus exhibits distinct patterns of network activity that are
      dependent on the interaction between inhibitory and excitatory transmission.
      Kainate receptors are ideally positioned to regulate this activity by virtue of
      their ability to regulate presynaptic function in GABAergic interneurones.
      Indeed, kainate receptors are highly expressed in neonatal hippocampal
      interneurones, yet the role and mechanisms by which they might regulate neonatal
      circuitry are unexplored. To address this we investigated the kainate receptor
      dependent regulation of GABAergic transmission onto neonatal CA1 pyramidal
      neurones. Kainate receptor activation produced two distinct opposing effects, a
      very large increase in the frequency of spontaneous IPSCs, and a robust
      depression of evoked GABAergic transmission. The up-regulation of spontaneous
      transmission was due to activation of somatodendritic and axonal receptors while
      the depression of evoked transmission could be fully accounted for by a direct
      regulation of GABA release by kainate receptors located at the terminals. None of
      the effects of kainate receptor agonists were sensitive to GABAB receptor
      antagonists, nor was there any postsynaptic kainate receptor-dependent effects
      observed in CA1 pyramidal cells that could account for our findings. Our data
      demonstrate that kainate receptors profoundly regulate neonatal CA1 GABAergic
      circuitry by two distinct opposing mechanisms, and indicate that these two
      effects are mediated by functionally distinct populations of receptors. Thus
      kainate receptors are strategically located to play a critical role in shaping
      early hippocampal network activity and by virtue of this have a key role in
      hippocampal development.

PMID- 15946970
TI  - Neuropeptide and calcium-binding protein gene expression profiles predict
      neuronal anatomical type in the juvenile rat.
AB  - Neocortical neurones can be classified according to several independent criteria:
      morphological, physiological, and molecular expression (neuropeptides (NPs)
      and/or calcium-binding proteins (CaBPs)). While it has been suggested that
      particular NPs and CaBPs characterize certain anatomical subtypes of neurones,
      there is also considerable overlap in their expression, and little is known about
      simultaneous expression of multiple NPs and CaBPs in morphologically
      characterized neocortical neurones. Here we determined the gene expression
      profiles of calbindin (CB), parvalbumin (PV), calretinin (CR), neuropeptide Y
      (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM) and
      cholecystokinin (CCK) in 268 morphologically identified neurones located in
      layers 2-6 in the juvenile rat somatosensory neocortex. We used patch-clamp
      electrodes to label neurones with biocytin and harvest the cytoplasm to perform
      single-cell RT-multiplex PCR. Quality threshold clustering, an unsupervised
      algorithm that clustered neurones according to their entire profile of expressed
      genes, revealed seven distinct clusters. Surprisingly, each cluster
      preferentially contained one anatomical class. Artificial neural networks using
      softmax regression predicted anatomical types at nearly optimal statistical
      levels. Classification tree-splitting (CART), a simple binary neuropeptide
      decision tree algorithm, revealed the manner in which expression of the multiple
      mRNAs relates to different anatomical classes. Pruning the CART tree revealed the
      key predictors of anatomical class (in order of importance: SOM, PV, VIP, and
      NPY). We reveal here, for the first time, a strong relationship between specific
      combinations of NP and CaBP gene expressions and the anatomical class of
      neocortical neurones.

PMID- 15946972
TI  - Selective recruitment of single motor units in human flexor digitorum
      superficialis muscle during flexion of individual fingers.
AB  - Flexor digitorum superficialis (FDS) is an extrinsic multi-tendoned muscle which
      flexes the proximal interphalangeal joints of the four fingers. It comprises four
      digital components, each with a tendon that inserts onto its corresponding
      finger. To determine the degree to which these digital components can be
      selectively recruited by volition, we recorded the activity of a single motor
      unit in one component via an intramuscular electrode while the subject
      isometrically flexed each of the remaining fingers, one at a time. The finger on
      which the unit principally acted was defined as the 'test finger' and that which
      flexed isometrically was the 'active' finger. Activity in 79 units was recorded.
      Isometric finger flexion forces of 50% maximum voluntary contraction (MVC)
      activated less than 50% of single units in components of FDS acting on fingers
      that were not voluntarily flexed. With two exceptions, the median recruitment
      threshold for all active-test finger combinations involving the index, middle,
      ring and little finger test units was between 49 and 60% MVC (60% MVC being the
      value assigned to those not recruited). The exceptions were flexion of the little
      finger while recording from ring finger units (median: 40% MVC), and vice versa
      (median: 2% MVC). For all active-test finger combinations, only 35/181 units were
      activated when the active finger flexed at less than 20% MVC, and the fingers
      were adjacent for 28 of these. Functionally, to recruit FDS units during grasping
      and lifting, relatively heavy objects were required, although systematic
      variation occurred with the width of the object. In conclusion, FDS components
      can be selectively activated by volition and this may be especially important for
      grasping at high forces with one or more fingers.

PMID- 15946971
TI  - The influence of small fibre muscle mechanoreceptors on the cardiac vagus in
      humans.
AB  - We have previously shown that activation of muscle receptors by passive stretch
      (PS) increases heart rate (HR) with little change in blood pressure (BP). We
      proposed that PS selectively inhibits cardiac vagal activity. We attempted to
      test this by performing PS during experimental alterations in vagal tone. Large
      decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic
      exercise. Milder alterations in vagal tone were achieved by altering carotid
      baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps
      surae was tested in 14 healthy human volunteers. BP, ECG and respiration were
      recorded. PS alone caused a significant decrease (P < 0.05) in R-R interval (962
      +/- 76 ms at baseline compared to 846 +/- 151 ms with PS), and showed a reduction
      in HR variability, which was not significant. The decrease in R-R interval with
      PS was significantly less (P < 0.05, n = 3) following administration of
      glycopyrrolate (-8.1 +/- 4.5 ms) compared to PS alone (-54 +/- 11 ms), and also
      with PS during handgrip (+10 +/- 10 ms) compared with PS alone (-74 +/- 15 ms) (P
      < 0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but
      insignificant further decrease in R-R interval in response to PS (-107 +/- 17 ms
      compared to PS alone -96 +/- 13 ms, n = 5). Mild increases in vagal activity (NS)
      during PS resulted in smaller decreases in R-R interval (-39 +/- 5.5 ms) compared
      to PS alone (-86 +/- 17 ms) (P < 0.05, n = 8). BP was not significantly changed
      by stretch in any tests. The results indicate that amongst muscle receptors there
      is a specific group activated by stretch that selectively inhibit cardiac vagal
      tone to produce tachycardia.

PMID- 15946973
TI  - Proton modulation of recombinant GABA(A) receptors: influence of GABA
      concentration and the beta subunit TM2-TM3 domain.
AB  - Regulation of GABA(A) receptors by extracellular pH exhibits a dependence on the
      receptor subunit composition. To date, the molecular mechanism responsible for
      the modulation of GABA(A) receptors at alkaline pH has remained elusive. We
      report here that the GABA-activated current can be potentiated at pH 8.4 for both
      alphabeta and alphabeta gamma subunit-containing receptors, but only at GABA
      concentrations below the EC40. Site-specific mutagenesis revealed that a single
      lysine residue, K279 in the beta subunit TM2-TM3 linker, was critically important
      for alkaline pH to modulate the function of both alpha1beta2 and alpha1beta2
      gamma2 receptors. The ability of low concentrations of GABA to reveal different
      pH titration profiles for GABA(A) receptors was also examined at acidic pH. At pH
      6.4, GABA activation of alphabeta gamma receptors was enhanced at low GABA
      concentrations. This effect was ablated by the mutation H267A in the beta
      subunit. Decreasing the pH further to 5.4 inhibited GABA responses via alphabeta
      gamma receptors, whereas those responses recorded from alphabeta receptors were
      potentiated. Inserting homologous beta subunit residues into the gamma2 subunit
      to recreate, in alphabeta gamma receptors, the proton modulatory profile of
      alphabeta receptors, established that in the presence of beta2(H267), the
      mutation gamma2(T294K) was necessary to potentiate the GABA response at pH 5.4.
      This residue, T294, is homologous to K279 in the beta subunit and suggests that a
      lysine at this position is an important residue for mediating the allosteric
      effects of both acidic and alkaline pH changes, rather than forming a direct site
      for protonation within the GABA(A) receptor.

PMID- 15946974
TI  - High pathological response rate in locally advanced esophageal cancer after
      neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy
      schedule with protracted venous infusion of 5-fluorouracil and dose escalation of
      cisplatin, docetaxel and concurrent radiotherapy.
AB  - BACKGROUND: This phase I study was aimed at defining the toxicity profile and
      pathological response rate of a neoadjuvant schedule including weekly docetaxel
      and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant
      radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS:
      The schedule consisted of a first phase of chemotherapy alone and a second phase
      of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20
      mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29
      49; RT (40 Gy) started on day 29. In the following steps the doses were escalated
      up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50
      and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63
      concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46
      completed the planned treatment. During the concomitant phase, grade 3-4
      hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and
      non-hematological toxicities in six patients (13%) (or 7/179 cycles). A
      pathological downstaging was obtained in 59.6% of the cases (28/47): complete
      remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0)
      in eight patients, pT2 pN0 in three patients and partial response on the primary
      with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were
      considered stable and non-responders, respectively. In the last dose level, eight
      pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable
      dose was not formally defined because dose escalation was stopped at the last
      dose level. CONCLUSION: This schedule represents a feasible treatment and the
      high pathological response rate is extremely encouraging; the doses found in the
      last dose-level are the basis for an ongoing phase II study at our institution.

PMID- 15946975
TI  - Front-line doublets in advanced non-small cell lung cancer: The golden age for
      second line chemotherapy.

PMID- 15946976
TI  - Long-term persistence of molecular disease after histological remission in low
      grade gastric MALT lymphoma treated with H. pylori eradication. Lack of
      association with translocation t(11;18): a 10-year updated follow-up of a
      prospective study.
AB  - BACKGROUND: Localized low-grade gastric mucosa-associated lymphoid tissue (MALT)
      lymphoma can regress after Helicobacter pylori eradication, but IgV(H) gene
      monoclonality may persist. We studied the long-term histological and molecular
      follow-up of 24 patients and the possible association of t(11;18) with the
      persistent monoclonality. PATIENTS AND METHODS: From January 1994, 24 untreated
      patients with stage I low-grade gastric MALT lymphoma associated with H. pylori
      were prospectively studied. They all received eradication treatment and were
      sequentially followed-up with endoscopies for histological and molecular studies.
      Rearrangement of the IgV(H) gene was studied by PCR analysis. MALT1 locus
      alterations were studied by FISH. RESULTS: Twenty-two of the 24 patients (91%)
      achieved disappearance of the lymphoma. Eighteen (82%) of the 22 histologically
      cured patients and 16 of the 19 (84%) with long follow-up had monoclonality.
      Three patterns of development of IgV(H) gene rearrangements were observed: four
      patients (21%) had polyclonal rearrangements; eight (58%) had
      maintained/intermittent monoclonality and four (21%) had occasional
      monoclonality, mostly after H. pylori reinfection. Only one patient (6%) with
      persistent monoclonality relapsed. The remaining 18 patients maintained the
      remission, despite the persistent monoclonality in 15, for a median of 66 months
      (range 20-113). t(11;18) was not found in any of the patients with persistent
      monoclonality. Time and the number of endoscopies performed were not related with
      the occurrence of monoclonality. CONCLUSIONS: In stage I low-grade gastric MALT
      lymphoma eradication of H. pylori achieves prolonged histological remission in
      90% of patients, but molecular remission is not accomplished in most cases.
      Molecular disease persists for years, but is not associated with t(11;18).

PMID- 15946977
TI  - Neoadjuvant vinorelbine/epirubicin (VE) versus standard
      adriamycin/cyclophosphamide (AC) in operable breast cancer: analysis of response
      and tolerability in a randomised phase III trial (TOPIC 2).
AB  - BACKGROUND: Vinorelbine is active and well tolerated against advanced breast
      cancer but there are no published efficacy studies in early breast cancer. We
      have therefore carried out a randomised phase III neoadjuvant trial in operable
      breast cancer. PATIENTS AND METHODS: Patients with > or =3 cm operable breast
      carcinoma were randomised to receive either vinorelbine 25 mg/m(2) on days 1 and
      8 and epirubicin 60 mg/m(2) on day 1, 3 weekly for six cycles (VE) or doxorubicin
      60 mg/m(2) and cyclophosphamide 600 mg/m(2) i.v. on day 1, 3 weekly for six
      cycles (AC), prior to standard local therapy, and adjuvant endocrine therapy as
      appropriate. RESULTS: A total of 451 patients were randomised. Results for AC and
      VE, respectively, were: overall clinical response 73% and 74%, complete clinical
      remission 20% and 24%, pathological complete remission 12% and 12%, mastectomy
      rate 52% and 55%. None of these differences were significant. Dose reduction was
      required in 8% for AC and 20% for VE (P <0.001) (GSCF support not used).
      Significantly more grade 3/4 toxicity for nausea, vomiting and alopecia (despite
      scalp cooling) was seen for AC compared with VE but significantly less grade 3/4
      thrombophlebitis and neuropathy. CONCLUSIONS: Neoadjuvant VE is as effective as
      AC in early breast cancer and was better tolerated except for thrombophlebitis
      and neuropathy.

PMID- 15946978
TI  - Quality-adjusted survival in a crossover trial of letrozole versus tamoxifen in
      postmenopausal women with advanced breast cancer.
AB  - BACKGROUND: Results from a phase III study of postmenopausal women with advanced
      breast cancer demonstrated longer time to disease progression for patients taking
      letrozole versus tamoxifen. This analysis compares the trade-offs between
      progression-free survival and toxicity. DESIGN: Quality-adjusted survival was
      calculated using Q-TWiST (quality-adjusted time without symptoms or toxicity).
      Survival curves were partitioned into three health states: toxicity (TOX),
      disease progression (PROG) and periods without toxicity or disease progression
      (TWiST). The utility-weighted sum of the health state durations was derived and
      compared. RESULTS: There was not a significant difference in mean duration of
      serious adverse events prior to progression between the letrozole (n=453) and
      tamoxifen (n=454) groups (2.2 and 2 months, respectively). For TWiST, the mean
      duration for letrozole was 11.5 months, versus 8.5 months for tamoxifen (P
      <0.001). The mean duration of PROG was 11.5 months for letrozole and 12.7 months
      for tamoxifen (P=0.047). Using utility weights of 0.5 for TOX and PROG resulted
      in a 2.5-month difference in quality-adjusted survival favoring letrozole (P
      <0.0001). CONCLUSIONS: The longer time to disease progression with letrozole
      versus tamoxifen was achieved without increased time with adverse events and
      resulted in more quality-adjusted survival for patients on letrozole.

PMID- 15946979
TI  - Computed tomography and 18F-FDG positron emission tomography for therapy control
      of Hodgkin's and non-Hodgkin's lymphoma patients: when do we really need FDG-PET?
AB  - BACKGROUND: The aim of this study was to evaluate the accuracy of computed
      tomography (CT) and [(18)F]fluoro-deoxy-d-glucose positron emission tomography
      (FDG-PET) for prediction of progression-free survival of Hodgkin's disease (HD)
      and non-Hodgkin's lymphoma (NHL) patients after completion of therapy. PATIENTS
      AND METHODS: CT and FDG-PET were performed in 40 HD, 17 indolent NHL and 44
      aggressive NHL patients (29 women, 72 men; aged 41+/-14 years) in a median of 2
      months after therapy. Progression-free survival was evaluated using the Kaplan
      Meier method. Independent prognostic factors were identified by means of Cox
      proportional hazards model. RESULTS: CT imaging results were progressive disease
      (PD) in five, stable disease (SD) in 57, and partial response (PR) or complete
      remission (CR) in 39 patients. FDG-PET suggested residual lymphoma in 24
      patients. Three-year progression-free survival rates after exclusion of five PD
      patients were: 100% (PET negative; CT: PR or CR), 81% (PET negative; CT: SD), 21%
      (PET positive; CT: SD) and 0% (PET positive; CT: PR). FDG-PET (P<0.0001) and
      bulky disease (P <0.05) were identified as independent prognostic variables.
      CONCLUSIONS: Among lymphoma patients with PR and SD on CT, FDG-PET discriminated
      those destined to progress into a low risk of < or =20% and a high risk for
      recurrence of > or =80%.

PMID- 15946980
TI  - High-dose mitoxantrone-vinblastine-cyclophosphamide and autologous stem cell
      transplantation for stage III breast cancer: final results of a prospective
      multicentre study.
AB  - BACKGROUND: Stage III breast cancer patients continue to suffer high relapse and
      death rates despite standard chemotherapy regimens. High-dose alkylator
      chemotherapy does not further improve outcome. This phase II study evaluated a
      novel high-dose chemotherapy regimen which combined active breast cancer agents
      with differing mechanisms of action. PATIENTS AND METHODS: Eligibility included
      at least seven involved axillary nodes (AxLNs) for tumours <5 cm, at least four
      AxLNs for tumours >5 cm or locally advanced breast cancer (LABC). Patients
      received four cycles of fluorouracil-adriamycin-cyclophosphamide (FAC) followed
      by one cycle of mitoxantrone 63 mg/m(2)-vinblastine 12.5 mg/m(2)-cyclophosphamide
      6 g/m(2) (MVC) with autologous blood stem cell transplantation (ASCT). RESULTS:
      Between April 1995 and December 1998, 92 patients aged 21-65 years (median 45
      years) were enrolled, of whom 25 were treated preoperatively for LABC and 67 were
      treated postoperatively. Although there was no early treatment-related mortality,
      one late death occurred from secondary acute myeloid leukaemia. The 7-year event
      free and overall survival rates were 53% (95% confidence interval 42-64%) and 62%
      (95% CI 52-73%), respectively, with no significant difference between pre- and
      postoperative groups. CONCLUSION: FAC followed by MVC-ASCT is feasible and
      reasonably well tolerated, but does not result in improved survival rates
      compared with other conventional or high-dose regimens for stage III breast
      cancer.

PMID- 15946981
TI  - Open reading frame ssr2016 is required for antimycin A-sensitive photosystem I
      driven cyclic electron flow in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - Open reading frame ssr2016 encodes a protein with substantial sequence
      similarities to PGR5 identified as a component of the antimycin A-sensitive
      ferredoxin:plastoquinone reductase (FQR) in PSI cyclic photophosphorylation in
      Arabidopsis thaliana. We studied cyclic electron flow in Synechocystis sp. PCC
      6803 in vivo in ssr2016 deletion mutants generated either in a wild-type
      background or in a ndhB deletion mutant. Our results indicate that ssr2016 is
      required for FQR and that it operates in a parallel pathway to the NDH1 complex.
      The ssr2016 deletion mutants are high light sensitive, suggesting that FQR might
      be important in controlling redox poise under adverse conditions.

PMID- 15946982
TI  - Reactive oxygen species and root hairs in Arabidopsis root response to nitrogen,
      phosphorus and potassium deficiency.
AB  - Plant root sensing and adaptation to changes in the nutrient status of soils is
      vital for long-term productivity and growth. Reactive oxygen species (ROS) have
      been shown to play a role in root response to potassium deprivation. To determine
      the role of ROS in plant response to nitrogen and phosphorus deficiency, studies
      were conducted using wild-type Arabidopsis and several root hair mutants. The
      expression of several nutrient-responsive genes was determined by Northern blot,
      and ROS were quantified and localized in roots. The monitored genes varied in
      intensity and timing of expression depending on which nutrient was deficient. In
      response to nutrient deprivation, ROS concentrations increased in specific
      regions of the Arabidopsis root. Changes in ROS localization in Arabidopsis and
      in a set of root hair mutants suggest that the root hair cells are important for
      response to nitrogen and potassium. In contrast, the response to phosphorus
      deprivation occurs in the cortex where an increase in ROS was measured. Based on
      these results, we put forward the hypothesis that root hair cells in Arabidopsis
      contain a sensing system for nitrogen and potassium deprivation.

PMID- 15946983
TI  - Temperature and Light modulate the trans-delta3-hexadecenoic acid content of
      phosphatidylglycerol: light-harvesting complex II organization and non
      photochemical quenching.
AB  - The interaction of light and temperature in the modulation of the trans-delta3
      hexadecenoic acid (trans-16:1) content of phosphatidylglycerol (PG) in winter rye
      (Secale cereale L.) was assessed and related to the organization of light
      harvesting complex II (LHCII). Increasing the growth irradiance from 50 to 800
      micromol m(-2) s(-1) at 20 degrees C resulted in a 1.8-fold increase in the trans
      16:1 content in PG which favoured a greater preponderance of oligomeric LHCII,
      measured in vitro as the ratio of oligomer : monomer. Similar irradiance
      dependent increases were observed during growth at 5 degrees C; however, 1.4-fold
      lower trans-16:1 contents and lower LHCII oligomer : monomer ratios were observed
      compared with growth at 20 degrees C and the same irradiance. These trends were
      also observed under natural field conditions. Thus, the accumulation of trans
      16:1, as well as the organization of LHCII are modulated by both growth
      irradiance and growth temperature in an independent but additive manner. We also
      examined how changes in the supramolecular organization of LHCII affected the
      capacity for non-photochemical quenching (q(N)) and photoprotection via antenna
      quenching (q(O)). While q(O) was positively correlated with q(N), there was no
      correlation with either LHCII organization or xanthophyll cycle activity under
      the steady-state growth conditions examined.

PMID- 15946984
TI  - Laryngeal abductor paralysis can be a solitary manifestation of multiple system
      atrophy.

PMID- 15946986
TI  - Comment on: Guidelines for the antibiotic treatment of endocarditis in adults:
      report of the Working Party of the British Society for Antimicrobial
      Chemotherapy.

PMID- 15946987
TI  - Clinical audit of linezolid use in a large teaching hospital.
AB  - OBJECTIVES: Linezolid, the first available agent in the new class of
      oxazolidinone antibiotics, represents a significant advance in the management
      options available for combating methicillin-resistant Staphylococcus aureus
      (MRSA) infections. In the UK it was launched for clinical use in 2001. The aim of
      this study was to audit the clinical use of linezolid and compliance with the
      guidelines of the hospital antibiotic committee. METHODS: Our hospital antibiotic
      committee agreed clinical indications for linezolid use. We undertook an audit of
      compliance with these recommendations and also reviewed its use in terms of the
      source of infection, microbiology, duration of therapy, side-effects and choice
      of previous treatment. RESULTS: Seventy-seven inpatients prescribed linezolid in
      Ninewells Hospital in the 3 years between March 2001 and September 2003 were
      audited. Overall compliance with our local recommendations appears to be very
      good. The main justification for using linezolid is the presence of existing or
      worsening renal dysfunction or poor venous access (34%) or lack of tolerance or
      clinical failure following glycopeptide monotherapy or combination therapy (32%).
      Skin and soft tissue infections (26%) were the most frequently diagnosed
      infections, although an increasing number of patients appear to receive linezolid
      for the treatment of lower respiratory tract infections, primarily in the ICU for
      nosocomial or ventilator-associated pneumonia. MRSA organisms were the most
      common cause of microbiologically proven treated infections [n = 43 (56%)].
      Disappointingly, only 34 out of 77 patients had case record documentation of
      prior approval by an infection specialist. CONCLUSIONS: The use of linezolid in
      our hospital appears to follow local guidelines, but the quality of information
      recorded in the notes could be optimized. Consequently, a linezolid mandatory
      order form to be completed by the attending prescribing clinician has been
      introduced, and will be subject to future evaluation. We recommend such specific
      antibiotic utilization reviews or audits of new agents introduced into clinical
      infection practice.

PMID- 15946988
TI  - Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration.
AB  - MT1-MMP is a type I transmembrane proteinase that promotes cell migration and
      invasion. Here, we report that MT1-MMP is palmitoylated at Cys574 in the
      cytoplasmic domain, and this lipid modification is critical for its promotion of
      cell migration and clathrin-mediated internalization. The palmitoylation
      defective mutant (C574A) failed to promote cell migration and was not
      internalized through clathrin pathway like wild-type, but it was internalized
      through the caveolae pathway. Reintroducing a cysteine at different positions in
      the cytoplasmic tail of the C574A mutant revealed that the position of the
      palmitoylated cysteine relative to LLY573, a motif that interacts with mu2
      subunit of adaptor protein 2, is critical for the cell motility-promoting
      activity of MT1-MMP and its clathrin-mediated internalization. Taken together,
      palmitoylation of MT1-MMP is one of the key posttranslational modifications that
      determines MT1-MMP-dependent cell migration.

PMID- 15946989
TI  - Monoamine oxidase-A is a major target gene for glucocorticoids in human skeletal
      muscle cells.
AB  - Skeletal myopathy is a common complication of endogenous and exogenous
      glucocorticoid excess, yet its pathogenetic mechanisms remain unclear. There is
      accumulating evidence that mitochondrial dysfunction and oxidative stress are
      involved in this process. To explore the glucocorticoid-induced transcriptional
      adaptations that may affect mitochondrial function in skeletal muscle, we studied
      gene expression profiles in dexamethasone-treated primary human skeletal myocytes
      using a cDNA microarray, which contains 501 mitochondria-related genes. We found
      that monoamine oxidase A (MAO-A) was the most significantly up-regulated gene.
      MAO-A is the primary enzyme metabolizing catecholamines and dietary amines, and
      its role in skeletal muscle remains largely unexplored. Dexamethasone induced
      dose- and time-dependent increases of MAO-A gene and protein expression, while
      its effects on MAO-B were minimal. Both the glucocorticoid receptor (GR) and the
      Sp1 transcription factor were required for dexamethasone-induced MAO-A mRNA
      expression, as blockade of the GR with RU 486 or ablation of Sp1 binding with
      mithramycin abrogated MAO-A mRNA induction. The observed dexamethasone effect was
      biologically functional, as this steroid significantly increased MAO-mediated
      hydrogen peroxide production. We suggest that MAO-A-mediated oxidative stress can
      lead to cell damage, representing a novel pathogenetic mechanism for
      glucocorticoid-induced myopathy and a potential target for therapeutic
      intervention.

PMID- 15946990
TI  - Human hair follicles display a functional equivalent of the hypothalamic
      pituitary-adrenal axis and synthesize cortisol.
AB  - The skin and its major appendages are prominent target organs and potent sources
      of key players along the classical hypothalamic-pituitary axis, such as
      corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and
      alpha melanocyte stimulating hormone (alpha-MSH), and even express key
      steroidogenic enzymes. Therefore, it may have established local stress response
      systems that resemble the hypothalamic-pituitary-adrenal (HPA) axis. However,
      functional evidence that this is indeed the case in normal human skin in situ has
      still been missing. We show that microdissected, organ-cultured human scalp hair
      follicles respond to CRH stimulation by up-regulating proopiomelanocortin (POMC)
      transcription and immunoreactivity (IR) for ACTH and alpha-MSH, which must have
      been processed from POMC. CRH, alpha-MSH, and ACTH also modulate expression of
      their cognate receptors (CRH-R1, MC1-R, MC2-R). In addition, the strongest
      stimulus for adrenal cortisol production, ACTH, also up-regulates cortisol-IR in
      the hair follicles. Isolated human hair follicles secrete substantial levels of
      cortisol into the culture medium, and this activity is further up-regulated by
      CRH. CRH also modulates important functional hair growth parameters in vitro
      (hair shaft elongation, catagen induction, hair keratinocyte proliferation,
      melanin production). Finally, human hair follicles display HPA axis-like
      regulatory feedback systems, since the glucocorticoid receptor agonist
      hydrocortisone down-regulates follicular CRH expression. Thus, even in the
      absence of endocrine, neural, or vascular systemic connections, normal human
      scalp hair follicles directly respond to CRH stimulation in a strikingly similar
      manner to what is seen in the classical HPA axis, including synthesis and
      secretion of cortisol and activation of prototypic neuroendocrine feedback loops.

PMID- 15946991
TI  - Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble
      oligomers via a distinct folding pathway.
AB  - Dopamine (DA) and alpha-synuclein (alpha-SN) are two key molecules associated
      with Parkinson's disease (PD). We have identified a novel action of DA in the
      initial phase of alpha-SN aggregation and demonstrate that DA induces alpha-SN to
      form soluble, SDS-resistant oligomers. The DA:alpha-SN oligomeric species are not
      amyloidogenic as they do not react with thioflavin T and lack the typical amyloid
      fibril structures as visualized with electron microscopy. Circular dichroism
      studies indicate that in the presence of lipid membranes DA interacts with alpha
      SN, causing an alteration to the structure of the protein. Furthermore, DA
      inhibited the formation of iron-induced alpha-SN amyloidogenic aggregates,
      suggesting that DA acts as a dominant modulator of alpha-SN aggregation. These
      observations support the paradigm emerging for other neurodegenerative diseases
      that the toxic species is represented by a soluble oligomer and not the insoluble
      fibril.

PMID- 15946992
TI  - Targeting the beta-catenin/APC pathway: a novel mechanism to explain the
      cyclooxygenase-2-independent anticarcinogenic effects of celecoxib in human colon
      carcinoma cells.
AB  - Celecoxib, a cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory
      drug, is a new anticarcinogenic agent. Its antitumor effects depend on the one
      hand on its COX-2-inhibiting potency, but on the other hand on COX-2-independent
      mechanisms, which until now have not been fully understood. Here, we investigated
      whether celecoxib has an impact on the APC/beta-catenin pathway, which has been
      shown to play a pivotal role in the development of various cancers, especially of
      the colon. After only 2 h of treatment of human Caco-2 colon carcinoma cells with
      100 muM celecoxib, we observed a rapid translocation of beta-catenin from its
      predominant membrane localization to the cytoplasm. Inhibition of the glycogen
      synthase-kinase-3beta (GSK-3beta) by LiCl prevented this celecoxib-induced
      translocation, suggesting that phosphorylation of beta-catenin by the GSK-3beta
      kinase was essential for this release. Furthermore, the cytosolic accumulation
      was accompanied by a rapid increase of beta-catenin in the nuclei, starting
      already 30 min after celecoxib treatment. The DNA binding activity of beta
      catenin time dependently decreased 2 h after celecoxib treatment. After this
      cellular reorganization, we observed a caspase- and proteasome-dependent
      degradation of beta-catenin after 8 h of drug incubation. Celecoxib-induced beta
      catenin degradation was also observed in various other tumor cell lines (HCT-116,
      MCF-7, and LNCAP) but was not seen after treatment of Caco-2 cells with either
      the anticarcinogenic nonsteroidal anti-inflammatory drug R-flurbiprofen or the
      highly COX-2-selective inhibitor rofecoxib. These findings indicate that the
      anticarcinogenic effects of celecoxib can be explained, at least partly, by an
      extensive degradation of beta-catenin in human colon carcinoma cells.

PMID- 15946993
TI  - Mechanisms of erythropoietin-mediated cardioprotection during ischemia
      reperfusion injury: role of protein kinase C and phosphatidylinositol 3-kinase
      signaling.
AB  - Langendorff-perfused rat hearts treated with EPO exhibited significantly improved
      postischemic recovery of left ventricular developed pressure (LVDP) and reduced
      infarct size compared with control hearts. Perfusion with the
      mitogen/extracellular signal-regulated kinase (MEK) inhibitor U0126 just before
      and concomitant with EPO treatment abolished EPO-induced phosphorylation of the
      MEK substrate extracellular signal-regulated kinase (ERK) but had no effect of
      EPO-mediated cardioprotection. EPO treatment of the perfused hearts induced
      translocation of protein kinase C (PKC) epsilon isoform to the membrane fraction
      of the hearts and the protective effect of EPO was significantly inhibited by the
      PKC catalytic inhibitor chelerythrine added before and concomitant with EPO.
      These data demonstrate that EPO-mediated activation of the PKC signaling pathway
      before or during ischemia is required for the cardioprotective effect of EPO
      during ischemia-reperfusion injury. Perfusion with the phosphatidylinositol 3
      kinase (PI3K) inhibitors LY294002 or wortmannin just before and concomitant with
      EPO treatment attenuated EPO-induced phosphorylation of the PI3K substrate Akt
      but had no effect on EPO-mediated cardioprotection. However, when wortmannin was
      added during EPO treatment and continued during reperfusion, EPO-mediated
      cardioprotection was significantly inhibited. We also show that postischemia EPO
      treatment at the onset of reperfusion significantly improved recovery of LVDP and
      reduced infarct size. Postischemia cardioprotection by EPO required the PI3K
      pathway but was not affected by inhibition of PKC at the time of EPO treatment.

PMID- 15946994
TI  - Alterations of beta-tubulin isotypes in breast cancer cells resistant to
      docetaxel.
AB  - Docetaxel is one of the most active drugs used to treat breast cancer. The
      cellular target of docetaxel is the microtubule, specifically the beta-tubulin
      subunit, that comprises a series of isotypes and that can modulate function. This
      study has examined the role of alteration in beta-tubulin isotypes in vitro and
      has sequenced the beta-tubulin gene to determine if there were mutations, both of
      which may represent important mechanisms of acquired resistance to docetaxel.
      Breast cancer cells, MCF-7 (oestrogen-receptor positive) and MDA-MB-231,
      (oestrogen-receptor negative) were made resistant to docetaxel in vitro.
      Expression of beta-tubulin isotypes (class I, II, III, IVa, IVb, and VI) was
      determined at the RNA and protein level using RT-PCR and western analysis,
      respectively. DNA sequencing evaluated the beta-tubulin gene. At the mRNA level,
      class I, II, III, and IVa beta-tubulin mRNA isotypes were over-expressed in
      docetaxel-resistant MCF-7 cells when compared with the docetaxel-sensitive
      parental cells. However, class VI beta-tubulin mRNA isotype expression was
      decreased in resistant cells. In MDA-MB-231 cells, there was a decrease in
      expression of the class I and class IVa beta-tubulin mRNA. However, there were
      increased expressions in class II, IVb, and VI beta-tubulin mRNA isotypes in
      resistant cells. Western analysis has confirmed corresponding increases in beta
      tubulin protein levels in MCF-7 cells. However, in MDA-MB-231 cells, there were
      decreased protein levels for class II and class III beta-tubulin. This study
      demonstrates that altered expression of mRNA beta-tubulin isotypes and modulation
      of beta-tubulin protein levels are associated with acquired docetaxel resistance
      in breast cancer cells. This allows further understanding and elucidation of
      mechanisms involved in resistance to docetaxel.

PMID- 15946995
TI  - In a flexible antagonist protocol, earlier, criteria-based initiation of GnRH
      antagonist is associated with increased pregnancy rates in IVF.
AB  - BACKGROUND: The purpose of the study was to assess ongoing pregnancy rates across
      groups of patients treated by IVF, which were defined according to criteria aimed
      at the prevention of premature LH surge and used for initiating GnRH antagonist.
      METHODS: This is a prospective observational cohort study. During the last 3
      years, in IVF-ICSI patients undergoing controlled ovarian stimulation (COS) with
      the antagonist protocol, the antagonist administration was initiated according to
      at least one of the following patient-specific criteria: (i) at least one
      follicle measuring >14 mm; (ii) estradiol levels >600 pg/ml; and (iii) LH levels
      >10 IU/l. Based upon these criteria, 208 cases of normal responders were analysed
      and categorized into three groups according to the starting day of the regimen:
      group D4 (n = 40) for day 4, group D5 (n = 98) for day 5 and group D6 (n = 70)
      for day 6. The main outcome measure was the ongoing pregnancy rate per started
      cycle. RESULTS: The total number of patients in the D4 and D5 groups (138 out of
      208), who received the antagonist earlier, was considerably larger compared with
      that of D6 (70 out of 208). Ongoing pregnancy rates were 37.5, 34.7 and 18.6% for
      groups D4, D5 and D6, respectively. Patients who initiated the GnRH antagonist on
      days 4 and 5 had statistically significant higher pregnancy rates compared with
      day 6. Rapid response, causing earlier antagonist administration initiation,
      according to the proposed criteria for the prevention of premature LH surges, and
      the absence of premature luteinization, as evidenced by normal progesterone
      levels on HCG day, were found to be independent positive predictive factors for
      favourable IVF outcome. CONCLUSIONS: The employment of an algorithm of criteria,
      aimed at the prevention of premature LH surges in a flexible antagonist protocol,
      resulted in antagonist initiation earlier than on stimulation day 6 in a
      significant proportion of patients. In those patients, a higher pregnancy rate
      was observed.

PMID- 15946996
TI  - Effect on expression of RT1-A and RT1-DM molecules of treatment with interferon
      gamma at the maternal--fetal interface of pregnant rats.
AB  - BACKGROUND: Recent studies suggest a role for interferon-gamma (IFN-gamma) in the
      pregnancy process. METHODS: The expression of non-classical class II major
      histocompatibility complex (RT1-DM) antigens and classical class I major
      histocompatibility complex (RT1-A) antigens induced by IFN-gamma was examined by
      reverse transcription-PCR, western blotting and immunohistochemistry. RESULTS:
      IFN-gamma treatment increased expression of RT1-DM and RT1-A during early
      pregnancy and decreased them during mid pregnancy at the maternal-fetal
      interface. In late pregnancy, expression of RT1-A decreased in placenta and
      increased in uterus, and RT1-DM increased in both placenta and uterus with IFN
      gamma treatment compared with untreated controls. Immunohistochemical studies
      suggested that in early pregnancy, RT1-DM protein mainly localized to uterine
      luminal epithelium and glandular epithelium, and RT1-A mainly localized to
      decidual blood vessels and decidua basalis. During mid and late pregnancy, RT1-A
      mainly localized in decidual blood vessels and spongiotrophoblast cells of the
      junction zone. RT1-DM mainly localized in blood vessels and the labyrinthine zone
      during mid and late gestation. CONCLUSIONS: RT1-A and RT1-DM can both be
      expressed at the maternal-fetal interface during normal pregnancy. Their
      localizaion changed according to the period of pregnancy. IFN-gamma can modulate
      the expression of these two molecules during the whole pregnancy.

PMID- 15946997
TI  - Assessment of the integrity of human oocytes retrieved from cryopreserved ovarian
      tissue after xenotransplantation.
AB  - BACKGROUND: Previous studies showed that immature oocytes stored in ovarian
      tissue could develop to the mature stage after transplantation. However, the
      quality and competency of the oocytes developed in xenografted ovarian tissue
      have never been investigated. As a pilot study to investigate this uncharted
      issue, we evaluated microtubule organization and chromatin configuration of human
      oocytes harvested from xenografted frozen-thawed ovarian tissue. METHODS: Frozen
      thawed human ovarian tissue was transplanted into severe combined immunodeficient
      mice. All animals were stimulated with gonadotrophin from 20 weeks after
      transplantation. Grafts were recovered 36 h after hCG administration. The oocytes
      were retrieved from the antral follicles (>2 mm diameter), cultured in vitro,
      stained for microtubule and chromatin localization. RESULTS: Five oocytes from 21
      female mice and seven oocytes from nine male mice were retrieved.
      Immunocytochemical examinations of these oocytes after in vitro maturation
      revealed only two developed to the metaphase II stage. Most oocytes were between
      prophase and metaphase with abnormal microtubule organization and chromatin
      configuration. CONCLUSIONS: Immature oocytes in stored human ovarian tissue can
      grow to maturity in host animals after xenotransplantation. Retrieval of oocytes
      from the xenograft can be carried out and is reproducible. However, many oocytes,
      grown in host animals and further matured in vitro, showed aberrant microtubule
      organization and chromatin patterns.

PMID- 15946998
TI  - ICSI for treatment of human immunodeficiency virus and hepatitis C virus
      serodiscordant couples with infected male partner.
AB  - BACKGROUND: Assisted reproductive technology with semen washing can offer a
      significant reduction in risk of sexual and vertical transmission of human
      immunodeficiency virus (HIV) and hepatitis C virus (HCV) in serodiscordant
      couples with infected male partner. METHODS: Among couples coming to our centre
      for reproductive problems from January 2001 to December 2003, we selected 43
      couples with seropositive male and seronegative female: 25 couples with HIV
      seropositive males, 10 couples with HIV/hepatitis C virus (HCV)-seropositive
      males and eight couples with HCV-seropositive males. Sperm samples were washed
      and used for ICSI. RESULTS: Seventy-eight cycles of ICSI were performed. The mean
      fertilization rate was 70.34 +/- 20.14% (mean +/- SD). A mean number of 3.55 +/-
      1.11 (range: 1-5) embryos of good quality was transferred for each patient. We
      obtained 22 pregnancies (21 singletons and one twin), with a pregnancy rate per
      transfer of 28.2% and an implantation rate per transfer of 15.2%. The cumulative
      pregnancy rate was 51.2%. At follow-up, no seroconversion was detected in any
      patient. CONCLUSIONS: Our data suggest that sperm wash and ICSI could be useful
      for reducing the risk of HIV and/or HCV transmission in serodiscordant couples
      with infected male wishing to have a child, irrespective of their fertility
      status.

PMID- 15946999
TI  - The derivation of two additional human embryonic stem cell lines from day 3
      embryos with low morphological scores.
AB  - BACKGROUND: Immune rejection can lead to the failure of human embryonic stem cell
      (hES cell) transplantation. One approach to address the problem is to establish
      hES cell line banks. Due to the limited source of human embryos and to ethical
      reasons, the hES cell lines are not readily available. This study was undertaken
      to determine whether discarded day 3 embryos with low morphological scores could
      develop into blastocysts and produce hES cell lines. METHODS: A total of 130 day
      3 embryos with low morphological scores were cultured to blastocyst stage, and
      inner cell masses (ICM) were isolated by immunosurgery. Colonies derived from the
      ICM were passaged every 4-7 days and evaluated for cell surface markers,
      differentiation potentials and karyotypes. RESULTS: A total of 19 blastocysts
      were obtained from 130 embryos (quality score <16), which resulted in the
      formation of 10 ICM, and two cell lines. Both cell lines satisfied the criteria
      that characterize pluripotent hES cells. CONCLUSION: Our results suggest that a
      subset with poor quality day 3 embryos judged on the basis of morphological
      assessment can form blastocysts and give rise to hES cell lines.

PMID- 15947000
TI  - Exposure to bisphenol A is associated with recurrent miscarriage.
AB  - BACKGROUND: Little is known about the influence of high exposure to bisphenol A
      on recurrent miscarriage and immunoendocrine abnormalities. METHODS: Serum
      bisphenol A, antiphospholipid antibodies (aPLs), antinuclear antibodies (ANAs),
      natural killer cell (NK) activity, prolactin, progesterone, thyroid-stimulating
      hormone (TSH) and free T4 were examined in 45 patients with a history of three or
      more (3-11) consecutive first-trimester miscarriages and 32 healthy women with no
      history of live birth and infertility. Subsequent pregnancy outcome and embryonic
      karyotype of abortuses were examined prospectively. RESULTS: The mean+/-SD values
      for bisphenol A in patients were 2.59+/-5.23 ng/ml, significantly higher than the
      0.77+/-0.38 ng/ml found for control women (P=0.024). High exposure to bisphenol A
      was associated with the presence of ANAs but not hypothyroidism,
      hyperprolactinaemia, luteal phase defects, NK cell activity or aPLs. A high level
      of bisphenol A in itself did not predict subsequent miscarriage. CONCLUSION:
      Exposure to bisphenol A is associated with recurrent miscarriage.

PMID- 15947001
TI  - Evidence that the cells responsible for marrow fibrosis in a rat model for
      hyperparathyroidism are preosteoblasts.
AB  - We examined proliferation of cells associated with PTH-induced peritrabecular
      bone marrow fibrosis in rats as well as the fate of those cells after withdrawal
      of PTH. Time-course studies established that severe fibrosis was present 7 d
      after initiation of a continuous sc PTH infusion (40 microg/kg.d). To ascertain
      cell proliferation, rats were coinfused for 1 wk with PTH (treated) or vehicle
      (control) and [3H]thymidine (1.5 mCi/rat). Groups of control and treated rats
      were killed immediately (d 0) and 1 wk (d 7) later. Few osteoblasts (Obs) and
      osteocytes in treated and control groups were radiolabeled on d 0. Peritrabecular
      cells expressing a fibroblastic (Fb) phenotype and surrounded by an extracellular
      matrix were not present in controls on either d 0 or d 7. Multiple cell layers of
      Fbs lined most (70%) of the bone surface on d 0 in treated rats and nearly all
      (85%) of the Fbs were radiolabeled. Fbs had entirely disappeared from bone
      surfaces on d 7. Eighty-five percent of the Obs on and 73% of the osteocytes
      within the active remodeling sites were radiolabeled. Immunohistochemistry
      revealed that Fbs induced by PTH treatment produced osteocalcin, osteonectin, and
      core binding factor-alpha1. These data provide compelling evidence that Fbs
      recruited to bone surfaces in response to a continuous PTH infusion undergo
      extensive proliferation, express osteoblast-specific proteins, and produce an
      extracellular matrix that is similar to osteoid. After restoration of normal PTH
      levels, Fbs differentiated to Obs, providing further evidence that Fbs are
      preosteoblasts.

PMID- 15947002
TI  - Reduction of insulin-stimulated glucose uptake in L6 myotubes by the protein
      kinase inhibitor SB203580 is independent of p38MAPK activity.
AB  - Insulin increases glucose uptake through translocation of the glucose transporter
      GLUT4 to the plasma membrane. We previously showed that insulin activates
      p38MAPK, and inhibitors of p38MAPKalpha and p38MAPKbeta (e.g. SB203580) reduce
      insulin-stimulated glucose uptake without affecting GLUT4 translocation. This
      observation suggested that insulin may increase GLUT4 activity via p38alpha
      and/or p38beta. Here we further explore the possible participation of p38MAPK
      through a combination of molecular strategies. SB203580 reduced insulin
      stimulation of glucose uptake in L6 myotubes overexpressing an SB203580-resistant
      p38alpha (drug-resistant p38alpha) but barely affected phosphorylation of the p38
      substrate MAPK-activated protein kinase-2. Expression of dominant-negative
      p38alpha or p38beta reduced p38MAPK phosphorylation by 70% but had no effect on
      insulin-stimulated glucose uptake. Gene silencing via isoform-specific small
      interfering RNAs reduced expression of p38alpha or p38beta by 60-70% without
      diminishing insulin-stimulated glucose uptake. SB203580 reduced photoaffinity
      labeling of GLUT4 by bio-LC-ATB-BMPA only in the insulin-stimulated state. Unless
      low levels of p38MAPK suffice to regulate glucose uptake, these results suggest
      that the inhibition of insulin-stimulated glucose transport by SB203580 is likely
      not mediated by p38MAPK. Instead, changes experienced by insulin-stimulated GLUT4
      make it susceptible to inhibition by SB203580.

PMID- 15947003
TI  - Cholesterol and steroid synthesizing smooth endoplasmic reticulum of
      adrenocortical cells contains high levels of proteins associated with the
      translocation channel.
AB  - Steroid-secreting cells are characterized by abundant smooth endoplasmic
      reticulum whose membranes contain many enzymes involved in sterol and steroid
      synthesis. Yet they have relatively little morphologically identifiable rough
      endoplasmic reticulum, presumably required for synthesis and maintenance of the
      smooth membranes. In this study, we demonstrate that adrenal smooth microsomal
      subfractions enriched in smooth endoplasmic reticulum membranes contain high
      levels of translocation apparatus and oligosaccharyltransferase complex proteins,
      previously thought confined to rough endoplasmic reticulum. We further
      demonstrate that these smooth microsomal subfractions are capable of effecting
      cotranslational translocation, signal peptide cleavage, and N-glycosylation of
      newly synthesized polypeptides. This shifts the paradigm for distinction between
      smooth and rough endoplasmic reticulum. Confocal microscopy revealed the proteins
      to be distributed throughout the abundant tubular endoplasmic reticulum in these
      cells, which is predominantly smooth surfaced. We hypothesize that the broadly
      distributed translocon and oligosaccharyltransferase proteins participate in
      local synthesis and/or quality control of membrane proteins involved in
      cholesterol and steroid metabolism in a sterol-dependent and hormonally regulated
      manner.

PMID- 15947004
TI  - Growth factors change nuclear distribution of estrogen receptor-alpha via mitogen
      activated protein kinase or phosphatidylinositol 3-kinase cascade in a human
      breast cancer cell line.
AB  - In the present study, to examine the dynamic changes in the localization of
      nuclear estrogen receptor (ER)alpha induced by growth factors, we used time-lapse
      confocal microscopy to directly visualized ERalpha fused with green fluorescent
      protein (GFP-ERalpha) in single living cells treated with epidermal growth factor
      (EGF) or IGF-I. We observed that 17beta-estradiol (E2) changed the normally
      diffuse distribution of GFP-ERalpha throughout the nucleoplasm to a hyperspeckled
      distribution within 10 min. Both EGF and IGF-I also changed the nuclear
      distribution of GFP-ERalpha, similarly to E2 treatment. However, the time courses
      of the nuclear redistribution of GFP-ERalpha induced by EGF or IGF-I were
      different from that induced by E2 treatment. In the EGF-treated cells, the GFP
      ERalpha nuclear redistribution was observed at 30 min and reached a maximum at 60
      min, whereas in the IGF-I-treated cells, the GFP-ERalpha nuclear redistribution
      was observed at 60 min and reached a maximum at 90 min. The EGF-induced
      redistribution of GFP-ERalpha was blocked by pretreatment with a MAPK cascade
      inhibitor, PD98059, whereas the IGF-I-induced redistribution of GFP-ERalpha was
      blocked by pretreatment with a phosphatidylinositol 3-kinase inhibitor, LY294002.
      Analysis using an activation function-2 domain deletion mutant of GFP-ERalpha
      showed that the change in the distribution of GFP-ERalpha was not induced by E2,
      EGF, or IGF-I treatment. These data suggest that MAPK and phosphatidylinositol 3
      kinase cascades are involved in the nuclear redistribution of ERalpha by EGF and
      IGF-I, respectively, and that the activation function-2 domain of ERalpha may be
      needed for the nuclear redistribution of ERalpha.

PMID- 15947005
TI  - Leptin improves insulin resistance and hyperglycemia in a mouse model of type 2
      diabetes.
AB  - Leptin has metabolic effects on peripheral tissues including muscle, liver, and
      pancreas, and it has been successfully used to treat lipodystrophic diabetes, a
      leptin-deficient state. To study whether leptin therapy can be used for treatment
      of more common cases of type 2 diabetes, we used a mouse model of type 2 diabetes
      (MKR mice) that show normal leptin levels and are diabetic due to a primary
      defect in both IGF-I and insulin receptors signaling in skeletal muscle. Here we
      show that leptin administration to the MKR mice resulted in improvement of
      diabetes, an effect that was independent of the reduced food intake. The main
      effect of leptin therapy was enhanced hepatic insulin responsiveness possibly
      through decreasing gluconeogenesis. In addition, the reduction of lipid stores in
      liver and muscle induced by enhancing fatty acid oxidation and inhibiting
      lipogenesis led to an improvement of the lipotoxic condition. Our data suggest
      that leptin could be a potent antidiabetic drug in cases of type 2 diabetes that
      are not leptin resistant.

PMID- 15947006
TI  - 17alpha-estradiol: a brain-active estrogen?
AB  - The estrogen 17beta-estradiol has profound effects on the brain throughout life,
      whereas 17alpha-estradiol, the natural optical isomer, is generally considered
      less active because it binds less avidly to estrogen receptors. On the contrary,
      recent studies in the brain document that 17alpha-estradiol elicits rapid and
      sustained activation of the MAPK/ERK and phosphatidylinositol 3-kinase-Akt
      signaling pathways; is neuroprotective, after an ischemic stroke and oxidative
      stress, and in transgenic mice with Alzheimer's disease; and influences spatial
      memory and hippocampal-dependent synaptic plasticity. The present study measured
      the endogenous content of 17alpha-estradiol in the brain and further clarified
      its actions and kinetics. Here we report that: 1) endogenous levels of 17alpha
      estradiol and its precursor estrone are significantly elevated in the postnatal
      and adult mouse brain and adrenal gland of both sexes, as determined by liquid
      chromatography/tandem mass spectrometry; 2) 17alpha-estradiol and 17beta
      estradiol bind estrogen receptors with similar binding affinities; 3) 17alpha
      estradiol transactivates an estrogen-responsive reporter gene; and 4) unlike
      17beta-estradiol, 17alpha-estradiol does not bind alpha-fetoprotein or SHBG, the
      estrogen-binding plasma proteins of the developing rodent and primate,
      respectively. 17alpha-Estradiol was also found in the brains of gonadectomized or
      gonadectomized/adrenalectomized mice, supporting the hypothesis that 17alpha
      estradiol is locally synthesized in the brain. These findings challenge the view
      that 17alpha-estradiol is without biological significance and suggest that
      17alpha-estradiol and its selective receptor, ER-X, are not part of a classical
      hormone/receptor endocrine system but of a system with important
      autocrine/paracrine functions in the developing and adult brain. 17alpha
      Estradiol may have enormous implications for hormone replacement strategies at
      the menopause and in the treatment of such neurodegenerative disorders as
      Alzheimer's disease and ischemic stroke.

PMID- 15947007
TI  - Thyroid hormones: rapid reply by surface delivery only.

PMID- 15947009
TI  - Bayesian inference for prevalence and diagnostic test accuracy based on dual
      pooled screening.
AB  - We propose a useful protocol for the problem of screening populations for low
      prevalence characteristics such as HIV or drugs. Current HIV screening of blood
      that has been donated for transfusion involves the testing of individual blood
      units with an inexpensive enzyme-linked immunosorbent assay test and follow-up
      with a more accurate and more expensive western blot test for only those units
      that tested positive. Our cost-effective pooling strategy would enhance current
      methods by making it possible to accurately estimate the sensitivity and
      specificity of the initial screening test, and the proportion of defective units
      that have passed through the system. We also provide a method of estimating the
      distribution of prevalences for the characteristic throughout the population or
      subpopulations of interest.

PMID- 15947010
TI  - Clinical and anthropometric profile of children with celiac disease in Punjab
      (North India).
AB  - This prospective study was carried out to evaluate the clinical and
      anthropometric profile of 71 children confirmed to have celiac disease on the
      basis of clinical features, duodenal biopsy and unequivocal improvement on gluten
      free diet. Serological tests were performed in 35 cases. The patients were
      divided into three age groups <5 years, 5-10 years, and >10 years as per the age
      of presentation to the hospital. Mean age was 8.7 years with a slight female
      preponderance. Diarrhea was the commonest presentation in group I and failure to
      thrive in group III. All patients in group III, had weight for age (w/a) <3rd
      percentile and majority (83 per cent) had short stature, with delayed puberty in
      all. All children had significant improvement in symptoms and growth on gluten
      restriction. None of the patients had been suspected to have celiac disease
      before, which signifies that in spite of increasing incidence of celiac disease,
      this disease is grossly under-diagnosed in North India where wheat is the staple
      diet. It is essential to make an early diagnosis of celiac disease in children to
      prevent growth delay.

PMID- 15947011
TI  - Infant and young child feeding in western Uganda: knowledge, practices and socio
      economic correlates.
AB  - In a cross-sectional household survey conducted in the rural district of Hoima,
      western Uganda, 720 child/mother pairs were recruited using a two-stage cluster
      design. Infant and young child feeding knowledge and practices were assessed in
      relation to recommendations and household socio-economic factors. Age specific
      feeding patterns were described using frequencies, proportions and life-tables.
      Logistic regressions were done with feeding practice as dependent and socio
      economic factors as independent variables. Breastfeeding was universal (99%) with
      a median duration of 21 months. Pre-lacteal use was high (43%), with educated
      mothers more prone to the practice. Using a 24-hour recall: the median duration
      of exclusive breastfeeding was 3.5 months; 10% of infants were bottle-fed; 92% of
      the 0-5 month-old infants breastfed 6 or more times; 21% of 2-3 month-olds
      received complementary food instead of breast milk only and 19% of 6-8 month-olds
      were only breastfed instead of receiving complementary food. Of children 12
      months and above, 42% were complemented twice or less and 49% complemented 3 or 4
      times. Only 36% of breastfeeding children between 6-23 months received dairy
      milk. Over 50% of mothers did not know that adding oil to complementary food
      could improve it. The least poor were more likely, than the poorest, to use dairy
      milk (OR 3.9, CI 1.6-9.6); and educated mothers were more likely to prepare
      special complementary foods than the un-educated (OR 2.7, CI 1.1-6.2). Emphasis
      should be on promotion of exclusive breastfeeding, timeliness of complementary
      feeding and socio-economic empowerment.

PMID- 15947012
TI  - The first 5 years of the family clinic for HIV at Tygerberg Hospital: family
      demographics, survival of children and early impact of antiretroviral therapy.
AB  - BACKGROUND: Family clinics address the problems of HIV-infected children and
      their families. The aims were to document demographics of the children and
      caregivers attending the Family Clinic for HIV at Tygerberg Academic Hospital
      (TAH) and to investigate factors affecting disease progression in children.
      METHODS: A retrospective folder review of children and parents attending the
      Family Clinic at TAH between January 1997 and December 2001, a period noted for
      its lack of antiretroviral treatment. RESULTS: Of 432 children seen for testing,
      274 children, median age 16.9 months, were HIV-infected. During follow-up, 46
      children died (median age 23 months) and 113 were lost to follow-up. The majority
      of children were malnourished. Those <2 years of age had lower weight for age Z
      scores (WAZ) than older children (p<0.001). At presentation, 47 per cent were in
      clinical stage B and two-thirds had moderate or severe CD4+ T cell depletion.
      Seventeen children had received highly active antiretroviral therapy (HAART), 12
      dual and 31 monotherapy. HAART was associated with improved survival compared to
      dual or monotherapy. Risk of death was reduced from eleven-fold for a WAZ <-4 to
      four-fold between -2 and -3. There was no association with immunological and
      clinical classification at entry and risk of mortality. Only 18 per cent of
      parents were evaluated in the clinic. Non-parental care was documented for 25 per
      cent of families. CONCLUSIONS: A low WAZ is associated with poor survival in
      children. Nutritional status should receive more attention in HIV disease
      classification in children. Parent utilization of the clinic was inadequate. Even
      in the absence of HAART, extended survival in children is possible.

PMID- 15947013
TI  - Epidemiology of juvenile-onset inflammatory bowel disease in central Saudi
      Arabia.
AB  - There is limited information about inflammatory bowel disease in Arab children.
      Hence, the objective of this study was to report on the epidemiology of this
      condition in our community. Medical records were analysed for all children below
      18 years of age diagnosed with inflammatory bowel disease (IBD) and followed up
      in our institution over a period of 10 years. From 1993 to 2002, 50 consecutive
      children were diagnosed to have IBD. This gives an estimated incidence of 0.5
      cases/100 000/year and a prevalence of 5 cases/100 000 populations for the region
      of Riyadh, Saudi Arabia. Most of the children (90 per cent) were Saudi nationals
      and the female to male ratio was 1 : 0.6. The age range was between 5 and 18
      years with 16 per cent of the cases diagnosed in children below 12 years of age.
      Chronic ulcerative colitis was the commonest form accounting for 48 per cent,
      followed by Crohn's disease and indeterminate colitis in 38 per cent and 16 per
      cent of the children, respectively. The best agreement between colonoscopic and
      histopathologic findings (89 per cent) was in children with ulcerative colitis
      followed by normal findings and Crohn's disease in 63 per cent and 35 per cent of
      the cases, respectively. It was concluded that the incidence and prevalence of
      IBD in this report are lower than in any other population. Nevertheless,
      comparison with older data suggests that the incidence is increasing.

PMID- 15947014
TI  - The impact of HIV on the profile of paediatric admissions and deaths at Pelonomi
      Hospital, Bloemfontein, South Africa.

PMID- 15947015
TI  - Actinomycotic suppurative thyroiditis in a child.
AB  - AIM: To present a rare case of actinomycotic suppurative thyroiditis in an infant
      with provision of the etiology, pathogenesis, clinical findings and treatment of
      this rare disease. DESIGN: A report of an 18-month-old female infant who
      presented with fever, erythema, induration and tenderness of the neck. The
      patient had the diagnosis of acute suppurative thyroiditis after a series of
      laboratory evaluation. RESULT: She was treated successfully with surgical
      debridement and intravenous penicillin G. CONCLUSION: Although rare, Actinomyces
      spp. should be considered in the etiology of acute suppurative thyroiditis.
      Because of its fastidious nature the probability of positive culture is low,
      thus, the microbiology laboratory should be called in advance to make
      preparations before culture and transport.

PMID- 15947016
TI  - RONN: the bio-basis function neural network technique applied to the detection of
      natively disordered regions in proteins.
AB  - MOTIVATION: Recent studies have found many proteins containing regions that do
      not form well-defined three-dimensional structures in their native states. The
      study and detection of such disordered regions is important both for
      understanding protein function and for facilitating structural analysis since
      disordered regions may affect solubility and/or crystallizability. RESULTS: We
      have developed the regional order neural network (RONN) software as an
      application of our recently developed 'bio-basis function neural network' pattern
      recognition algorithm to the detection of natively disordered regions in
      proteins. The results of blind-testing a panel of nine disorder prediction tools
      (including RONN) against 80 protein sequences derived from the Protein Data Bank
      shows that, based on the probability excess measure, RONN performed the best.

PMID- 15947017
TI  - Sarment: Python modules for HMM analysis and partitioning of sequences.
AB  - Sarment is a package of Python modules for easy building and manipulation of
      sequence segmentations. It provides efficient implementation of usual algorithms
      for hidden Markov Model computation, as well as for maximal predictive
      partitioning. Owing to its very large variety of criteria for computing
      segmentations, Sarment can handle many kinds of models. Because of object
      oriented programming, the results of the segmentation are very easy tomanipulate.

PMID- 15947018
TI  - Refined phylogenetic profiles method for predicting protein-protein interactions.
AB  - MOTIVATION: The increasing availability of complete genome sequences provides
      excellent opportunity for the further development of tools for functional studies
      in proteomics. Several experimental approaches and in silico algorithms have been
      developed to cluster proteins into networks of biological significance that may
      provide new biological insights, especially into understanding the functions of
      many uncharacterized proteins. Among these methods, the phylogenetic profiles
      method has been widely used to predict protein-protein interactions. It involves
      the selection of reference organisms and identification of homologous proteins.
      Up to now, no published report has systematically studied the effects of the
      reference genome selection and the identification of homologous proteins upon the
      accuracy of this method. RESULTS: In this study, we optimized the phylogenetic
      profiles method by integrating phylogenetic relationships among reference
      organisms and sequence homology information to improve prediction accuracy. Our
      results revealed that the selection of the reference organisms set and the
      criteria for homology identification significantly are two critical factors for
      the prediction accuracy of this method. Our refined phylogenetic profiles method
      shows greater performance and potentially provides more reliable functional
      linkages compared with previous methods.

PMID- 15947019
TI  - A quantitative determination of multi-protein interactions by the analysis of
      confocal images using a pixel-by-pixel assessment algorithm.
AB  - MOTIVATION: Recent advances in confocal microscopy have allowed scientists to
      assess the expression, and to some extent, the interaction/colocalization of
      multiple molecules within cells and tissues. In some instances, accurately
      quantifying the colocalization of two or more proteins may be critical. This can
      require the acquisition of multiple Z plane images (Z stacks) throughout a
      specimen and, as such, we report here the successful development of a freeware,
      open-source image analysis tool, IMAJIN_COLOC, developed in PERL (v. 5.8, build
      806), using the PERLMagick libraries (ImageMagick). Using a pixel-by-pixel
      analysis algorithm, IMAJIN_COLOC can analyze images for antigen expression (any
      number of colors) and can measure all possible combinations of colocalization for
      up to three colors by analyzing a Z stack gallery acquired for each sample. The
      simultaneous (i.e. in a single pass) analysis of three-color colocalization, and
      batch analysis capabilities are distinctive features of this program. RESULTS: A
      control image, containing known individual and colocalized pixel counts, was used
      to validate the accuracy of IMAJIN_COLOC. As further validation, pixel counts and
      colocalization values from the control image were compared to those obtained with
      the software packaged with the Zeiss laser-scanning microscope (LSM AIM, version
      3.2). The values from both programs were found to be identical. To demonstrate
      the applicability of this program in addressing novel biological questions, we
      examined the role of neurons in eliciting an immune reaction in response to viral
      infection. Specifically, we successfully examined expression of the chemokine
      RANTES in measles virus (MV) infected hippocampal neurons and quantified changes
      in RANTES production throughout the disease period. The resultant quantitative
      data were also evaluated visually, using a gif image created during the analysis.
      AVAILABILITY: PERL (ActivePerl, version 5.8) is available at activestate.com; the
      PERLMagick libraries are available at imagemagick.org, and IMAJIN_COLOC, the
      source code and user documentation can be downloaded from
      http://www.fda.gov/cber/research/imaging/imageanalysis.htm.

PMID- 15947020
TI  - Thermodynamic properties of DNA sequences: characteristic values for the human
      genome.
AB  - MOTIVATION: Central to many molecular biology techniques as ubiquitous as PCR and
      Southern blotting is the design of oligonucleotide (oligo) probes and/or primers
      possessing specific thermodynamic properties. Here, we use validated theoretical
      methods to generate distributions of predicted thermodynamic properties for DNA
      oligos of various lengths. These distributions facilitate immediate appreciation
      of typical thermodynamic values for oligos of various lengths. RESULTS:
      Distributions of melting temperature (Tm), free energy (DeltaG(T)o), and fraction
      hybridized or fraction bound (Fb), are presented for oligos of length 10-50 bases
      sampled from the human genome. The effects of changing temperature, oligo and
      salt concentrations, constraining G+C content, and introducing mismatches are
      exemplified. Our results provide the first survey of typical and limiting
      thermodynamic values evaluated on a genomic scale. Described numbers comprise
      useful 'rules of thumb' that are applicable to most technologies dependent upon
      DNA oligo design.

PMID- 15947021
TI  - PEDSTATS: descriptive statistics, graphics and quality assessment for gene
      mapping data.
AB  - We describe a tool that produces summary statistics and basic quality assessments
      for gene-mapping data, accommodating either pedigree or case-control datasets.
      Our tool can also produce graphic output in the PDF format.

PMID- 15947022
TI  - Improving adherence to highly active anti-retroviral therapy in Africa: the DREAM
      programme in Mozambique.
AB  - Ensuring high levels of adherence to highly active anti-retroviral therapy
      (HAART) is a priority in treating people living with AIDS. This study reports the
      rates of adherence of patients served by DREAM (Drug Resource Enhancement against
      AIDS and Malnutrition) in the city of Matola, Mozambique. DREAM, an innovative
      programme tailored for Africa, was implemented by the Community of Sant'Egidio in
      August 2001. DREAM provides patients with anti-retroviral drugs and laboratory
      tests at no charge, and is based on a particular strategy of health education and
      organization of services designed for a population that is predominantly poor and
      has a low level of formal education. This study analyzes the adherence of 154
      patients over a period of 6 months. In evaluating adherence, two indicators were
      used: (1) the percentage of appointments kept for check-ups, tests and the
      collection of medicine, and (2) the overall change in the patients' blood
      chemistry over the 6-month period. Of the 154 patients, 127 (82.5%) kept more
      than 90% of their appointments. Adherence to the programme was further confirmed
      by a relevant increase of hemoglobin levels and CD4 counts, and a significant
      decrease in the viral loads among the 154 patients.

PMID- 15947023
TI  - Employee's perceived exposure to environmental tobacco smoke, passive smoking
      risk beliefs and attitudes towards smoking: a case study in a university setting.
AB  - Despite the growing literature on workplace smoking policies, few studies have
      focused on the implementation of such policies in university settings. Smoking in
      the workplace is still very common in many countries, including Spain. While the
      law is about to change and more non-smoking policies are to be implemented, it is
      not clear what kind of restrictions Spanish workers would find acceptable. This
      study investigated perceived exposure to environmental tobacco smoke (ETS),
      passive smoking risks beliefs and attitudes towards smoking at the University of
      Navarra (Spain). A questionnaire was sent by E-mail to 641 randomly selected
      employees and a response rate of 70.4% was obtained. The survey results suggest
      that 27.3% of the university employees were smokers and 26.6% were exposed to ETS
      on a daily basis. The majority of respondents (81.7%) supported a restrictive non
      smoking policy. Acceptance among active smokers was significantly lower (59.2
      versus 89.3%). Smoking prohibition with the provision of smoking areas was the
      most favored option (46.9%). Results suggest that employees are ready to restrict
      smoking in the university, but there was not enough support for a total ban.
      Employers considering adopting a ban on smoking should be encouraged to conduct a
      similar survey to identify potential barriers to policy implementation.

PMID- 15947024
TI  - The role of protein kinase C in regulation of TCDD-mediated CYP1A1 gene
      expression.
AB  - Cytochrome P450 1A1 (CYP1A1) is induced by halogenated and polycyclic aromatic
      hydrocarbons following activation of the aryl hydrocarbon receptor (AhR). Protein
      kinase C (PKC) has been implicated in the regulation of this response. In tissue
      culture, induction of PKC activity with phorbol esters synergizes the actions of
      TCDD-induced CYP1A1, while PKC inhibitors block induction of CYP1A1 by TCDD.
      Here, the actions of specific PKC inhibitors on CYP1A1 induction were examined
      using a HepG2 human cell line (TV101L) that carries a stably integrated firefly
      luciferase gene under control of the human CYP1A1 promoter (-1612/+293). TV101
      cells were treated with TCDD and either the kinase inhibitor staurosporine or one
      of the PKC inhibitors GF109203X, Go6983, or Go6976. Aryl hydrocarbon receptor
      dependent activation of CYP1A1-luciferase and cellular PKC activity were
      measured. TCDD treatment induced CYP1A1-luciferase activity in an AhR-dependent
      manner, as determined by binding of nuclear AhR to xenobiotic response elements
      (XREs). Dose-dependent inhibition of PKC activity by staurosporine was concordant
      with inhibition of TCDD-induced CYP1A1-luciferase activity. However, the PKC
      inhibitors GF109203X, Go6983, and Go6976 blocked PKC activity at concentrations
      independent of those necessary to block TCDD induction of CYP1A1-luciferase
      activity. For all inhibitors, reduction in CYP1A1-luciferase activity was
      independent of AhR activation, as determined by electrophoretic mobility shift
      analysis of TCDD-activated nuclear AhR. The specific PKC inhibitors did not
      significantly alter cytosolic or nuclear levels of AhR protein, whether alone or
      in combination with TCDD. These results suggested that PKC was not the sole
      factor responsible for regulation of CYP1A1.

PMID- 15947025
TI  - Gene expression profiling of 17beta-estradiol and genistein effects on mouse
      thymus.
AB  - Estrogen regulates thymic development and involution and modulates immune
      function. Despite its critical role in thymus, as well as in autoimmune
      disorders, the mechanism by which estrogen affects the thymus is not well
      understood. We previously reported that the estrogenic soy isoflavone genistein,
      as well as 17beta-estradiol (E2), could induce thymic involution, but genistein
      effects were only partially mediated through estrogen receptors. To provide
      insights into mechanisms of estrogenic effects in the thymus, we investigated
      thymic gene expression changes induced by E2 (125 ng/day) and genistein (1500 ppm
      in feed) in weanling mice using high-density DNA arrays. We identified several E2
      responsive genes involved in thymic development and thymocyte signaling during
      selection and maturation. Functional characterization indicated effects on genes
      involved in transcription, apoptosis, and the cell cycle. This study also
      identified changes in several E2-regulated transcripts essential to maintain
      immune self-tolerance. E2 upregulated more genes than genistein, while genistein
      downregulated more genes than E2. Though each treatment regulated several genes
      not altered by the other, there was considerable overlap in the genes regulated
      by E2 and genistein. Changes in transcription factors and cell cycle factors were
      consistent with decreases in cell proliferation induced by both genistein and E2.
      As indicated by the regulation of non-E2-responsive genes, genistein also induced
      unique effects through non-estrogenic mechanisms. The specific downregulation of
      the CD4 coreceptor transcript by genistein was consistent with the decline of
      CD4+ thymocytes in genistein-treated mice in our previous study. This is the
      first study identifying E2 and genistein target genes in the thymus. These
      findings provide new mechanistic insights toward explaining estrogen action on
      thymocyte development, selection, and maturation, as well as the effects of
      genistein on prenatal and neonatal thymic development and function.

PMID- 15947026
TI  - Forced uptake of trivalent and pentavalent methylated and inorganic arsenic and
      its cyto-/genotoxicity in fibroblasts and hepatoma cells.
AB  - Mammals are able to convert inorganic arsenic to mono-, di-, and trimethylated
      metabolites. In previous studies we have shown that the trivalent organoarsenic
      compounds are more toxic than their inorganic counterparts and that the toxicity
      is associated with the cellular uptake of the arsenicals. In the present study,
      we investigated cyto-/genotoxic effects of the arsenic compounds arsenate
      [As(i)(V)], arsenite [As(i)(III)], monomethylarsonic acid [MMA(V)],
      monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)],
      dimethylarsinous acid [DMA(III)], and trimethylarsine oxide [TMAO(V)] after an
      extended exposure time (24 h) and compared the uptake capabilities of fibroblasts
      (CHO-9 cells: Chinese hamster ovary) used for genotoxicity studies, with those of
      hepatic cells (Hep G2: hepatoma cell-line). To find out whether the arsenic
      compounds are bound to membranes or if they are present in the cytosol, the
      amount of arsenic was measured in whole-cell extracts and in membrane-removed
      cell extracts by inductively coupled plasma-mass spectrometry (ICP-MS). In
      addition, we forced the cellular uptake of the arsenic compounds into CHO-9 cells
      by electroporation and measured the intracellular arsenic concentrations before
      and after this procedure. Our results show that organic and inorganic arsenicals
      are taken up to a higher degree by fibroblasts compared to hepatoma cells. The
      arsenic metabolite DMA(III) was the most membrane permeable species in both cell
      lines and induced strong genotoxic effects in CHO-9 cells after an exposure time
      of 24 h. The uptake of all other arsenic species was relatively low (<1% by Hep
      G2 and <4% by CHO cells), but was dose-dependent. Electroporation increased the
      intracellular arsenic levels as well as the number of induced MN in CHO-9 cells.
      With the exception of As(i)(III) and DMA(III) in CHO-9 cells, the tested arsenic
      compounds were not bound to cell membranes, but were present in the cytosol. This
      may indicate the existence of DMA(III)-specific exporter proteins as are known
      for As(i)(III). Our results indicate that the uptake capabilities of arsenic
      compounds are highly dependent upon the cell type. It may be hypothesized that
      the arsenic-induced genotoxic effects observed in fibroblasts are due to the high
      uptake of arsenicals into this cell type. This may explain the high
      susceptibility of skin fibroblasts to arsenic exposure.

PMID- 15947028
TI  - Prior exposure to hypoxic-induced apnea impairs protective responses of newborn
      rats in an exposure-dependent fashion: influence of normoxic recovery time.
AB  - Experiments were carried out to determine whether prior exposure to hypoxic
      induced apnea impairs protective responses of newborn rats. Ninety-five, 5- to 6
      day-old rat pups were instrumented for respiratory measurements and placed prone
      in a metabolic chamber regulated to 37.0 degrees C. The time to first and last
      gasp as well as the number of gasps were determined on exposure to unrelenting
      hypoxia after each pup had experienced 0, 1, 2, 3, 4, 9, or 14 hypoxic-induced
      apnea/autoresuscitation cycles (HIA/AR) at 5-min intervals. Prior exposure to
      HIA/AR did not significantly alter the time to first gasp, but it decreased the
      time to last gasp after two HIA/AR and the number of gasps after three HIA/AR on
      exposure to unrelenting hypoxia. When the normoxic recovery time after 9 HIA/AR
      was varied from 5 to 120 min, the time to last gasp as well as the total number
      of gasps increased on exposure to unrelenting hypoxia but only at 120 min (i.e.,
      the number of gasps was similar but the time to last gasp was still decreased
      compared with that observed in naive animals exposed to unrelenting hypoxia).
      Thus prior exposure to hypoxic-induced apnea as may occur during obstructive
      sleep apnea or positional asphyxia decreases the number and duration of potential
      autoresuscitation producing gasps on exposure to unrelenting hypoxia for a period
      of up to and exceeding 120 min, respectively. The mechanism by which prior
      exposure to hypoxic-induced apnea influences the duration and number of hypoxic
      induced gasps is unknown.

PMID- 15947027
TI  - Effect of cigarette smoke on autoimmunity in murine and human systemic lupus
      erythematosus.
AB  - Several studies have found that smoking cigarettes is a risk factor for systemic
      lupus erythematosus (SLE). To examine this issue in a mouse model, we subjected
      pre-autoimmune MRL-lpr/lpr mice for 4 weeks to cigarette smoke to provide
      standardized smoke effluents equivalent to moderate or to heavy smoking habits
      for people. The spontaneous production of IgG anti-chromatin but not IgM anti
      chromatin, anti-denatured DNA, or rheumatoid factor antibodies was lower in mice
      exposed to 250 mg/m3 particulates from mainstream smoke, and this suppression of
      autoimmunity was sustained for 8 weeks (p < 0.02). In contrast to control mice
      anti-chromatin activity in smoke-exposed mice began to increase in 16-week-old
      mice, reaching levels at 6 months that were two- to three-fold higher than
      controls for IgG (p < 0.03) and 10-fold higher for IgM (p < 0.001). There was no
      significant effect on total IgG or IgM. In newly diagnosed SLE patients, smoking
      was negatively correlated with IgG anti-DNA antibodies (p < 0.03). However, of
      nine patients who discontinued smoking prior to diagnosis, eight had elevated IgG
      anti-DNA compared to 29/79 never smokers and 9/31 smokers (p < 0.01 compared to
      former smokers). Inhaled cigarette smoke appears to have a long-lasting
      immunosuppressive effect on T-cell-dependent autoimmune responses, although
      autoantibodies increase to supra-elevated levels after the suppressive effect has
      abated.

PMID- 15947029
TI  - Changes in lipoprotein lipase modulate tissue energy supply during stress.
AB  - We studied the variations caused by stress in lipoprotein lipase (LPL) activity,
      LPL-mRNA, and local blood flow in LPL-rich tissues in the rat. Stress was
      produced by body immobilization (Immo): the rat's limbs were taped to metal
      mounts, and its head was placed in a plastic tube. Chronic stress (2 h daily of
      Immo) decreased total LPL activity in mesenteric and epididymal white adipose
      tissue (WAT) and was accompanied by a weight reduction of these tissues. In limb
      muscle, heart, and adrenals, total LPL activity and mRNA levels increased, and,
      in plasma, LPL activity and mass also increased. Acute stress (30-min Immo)
      caused a decrease in total LPL activity only in retroperitoneal WAT and an
      increase in preheparin plasma active LPL, but the overall weight of this tissue
      did not vary significantly. We propose an early release of the enzyme from this
      tissue into the bloodstream by some unknown extracellular pathways or other local
      mechanisms. These changes in this key energy-regulating enzyme are probably
      induced by catecholamines. They modify the flow of energy substrates between
      tissues, switching the WAT from importer to exporter of free fatty acids and
      favoring the uptake by muscle of circulating triacylglycerides for energy supply.
      Moreover, we found that acute stress almost doubled blood flow in all WAT
      studied, favoring the export of free fatty acids.

PMID- 15947030
TI  - Differential serial sarcomere number adaptations in knee extensor muscles of rats
      is contraction type dependent.
AB  - Sarcomerogenesis, or the addition of sarcomeres in series within a fiber, has a
      profound impact on the performance of a muscle by increasing its contractile
      velocity and power. Sarcomerogenesis may provide a beneficial adaptation to
      prevent injury when a muscle consistently works at long lengths, accounting for
      the repeated-bout effect. The association between eccentric exercise,
      sarcomerogenesis and the repeated-bout effect has been proposed to depend on
      damage, where regeneration allows sarcomeres to work at shorter lengths for a
      given muscle-tendon unit length. To gain additional insight into this phenomenon,
      we measured fiber dynamics directly in the vastus lateralis (VL) muscle of rats
      during uphill and downhill walking, and we measured serial sarcomere number in
      the VL and vastus intermedius (VI) after chronic training on either a decline or
      incline grade. We found that the knee extensor muscles of uphill walking rats
      undergo repeated active concentric contractions, and therefore they suffer no
      contraction-induced injury. Conversely, the knee extensor muscles during downhill
      walking undergo repeated active eccentric contractions. Serial sarcomere numbers
      change differently for the uphill and downhill exercise groups, and for the VL
      and VI muscles. Short muscle lengths for uphill concentric-biased contractions
      result in a loss of serial sarcomeres, and long muscle lengths for downhill
      eccentric-biased contractions result in a gain of serial sarcomeres.

PMID- 15947031
TI  - Age-related differences in corticospinal control during functional isometric
      contractions in left and right hands.
AB  - The purpose of the study was to examine age-related differences in
      electromyographic (EMG) responses to transcranial magnetic stimulation (TMS)
      during functional isometric contractions in left and right hands. EMG responses
      were recorded from the first dorsal interosseus muscle following TMS in 10 young
      (26.6 +/- 1.3 yr) and 10 old (67.6 +/- 2.3 yr) right-handed subjects. Muscle
      evoked potentials (MEPs) and silent-period durations were obtained in the left
      and right hands during index finger abduction, a precision grip, a power grip,
      and a scissor grip, while EMG was held constant at 5% of maximum. For all tasks,
      MEP area was 30% (P < 0.001) lower in the left hand of old compared with young
      subjects, whereas there was no age difference in the right hand. The duration of
      the EMG silent period was 14% (P < 0.001) shorter in old (150.3 +/- 2.9 ms)
      compared with young (173.9 +/- 3.0 ms) subjects, and the age differences were
      accentuated in the left hand (19% shorter, P < 0.001). For all subjects, the
      largest MEP area (10-12% larger) and longest EMG silent period (8-19 ms longer)
      were observed for the scissor grip compared with the other three tasks, and the
      largest task-dependent change in these variables was observed in the right hand
      of older adults. These differences in corticospinal control in the left and right
      hands of older adults may reflect neural adaptations that occur throughout a
      lifetime of preferential hand use for skilled (dominant) and unskilled
      (nondominant) motor tasks.

PMID- 15947032
TI  - Contractile abilities of normal and "mini" triceps surae muscles from mice (Mus
      domesticus) selectively bred for high voluntary wheel running.
AB  - As reported previously, artificial selection of house mice caused a 2.7-fold
      increase in voluntary wheel running of four replicate selected lines compared
      with four random-bred control lines. Two of the selected lines developed a high
      incidence of a small-muscle phenotype ("mini muscles") in the plantar flexor
      group of the hindlimb, which apparently results from a simple Mendelian recessive
      allele. At generations 36-38, we measured wheel running and key contractile
      characteristics of soleus and medial gastrocnemius muscles from normal and mini
      muscles in mice from these selected lines. Mice with mini muscles ran faster and
      a greater distance per day than normal individuals but not longer. As expected,
      in mini-muscle mice the medial and lateral gastrocnemius muscles were
      approximately 54 and 45% the mass of normal muscles, respectively, but the
      plantaris muscles were not different in mass and soleus muscles were actually 30%
      larger. In spite of the increased mass, contractile characteristics of the soleus
      were unchanged in any notable way between mini and normal mice. However, medial
      gastrocnemius muscles in mini mice were changed markedly toward a slower
      phenotype, having slower twitches; demonstrated a more curved force-velocity
      relationship; produced about half the mass-specific isotonic power, 20-50% of the
      mass-specific cyclic work and power (only 10-25% the absolute power if the loss
      in mass is considered); and fatigued at about half the rate of normal muscles.
      These changes would promote increased, aerobically supported running activity but
      may compromise activities that require high power, such as sprinting.

PMID- 15947033
TI  - Evidence for the existence of an additional class of neuropeptide Y receptor
      sites in rat brain.
AB  - Five distinct neuropeptide Y (NPY) receptors have been cloned thus far. Selective
      agonists and antagonists have recently been developed allowing for detailed
      functional studies as to the pathophysiological role of a given subtype as well
      as receptor binding characteristics and distribution. To precisely investigate
      the discrete localization and ligand selectivity profile of Y4 and Y5 receptors,
      a series of selective molecules were used as radioligands and competitors in rat
      brain tissues. Binding data revealed that Y4 and Y5 receptor-related agonists and
      antagonists competed with high affinity for specific 125I-[Leu31,Pro34]human
      peptide YY (hPYY) binding in the presence of BIBO3304 [(R)-N-[[4
      (aminocarbonylaminomethyl)-phenyl]-methyl]-N2-(diphenylacetyl)-argininamide
      trifluoroacetate] to mask Y1 sites as well as specific 125I-labeled human
      pancreatic polypeptide (hPP) binding. Competition binding profiles were best
      fitted to a two-site model for both radioligands, suggesting the likely
      recognition of the Y4 and Y5 subtypes. We were surprised to find that the
      visualization of these specific binding sites by receptor autoradiography clearly
      revealed the distinct distribution of specific 125I-[Leu31,Pro34]hPYY (in
      presence of Y1 and Y5 blockers) and 125I-hPP (in presence of Y5 blocker) binding
      sites. Moreover, significant amounts of specific 125I-hPP binding were observed
      in the medial preoptic area, paraventricular nucleus of the hypothalamus,
      interpeduncular nucleus, and various brainstem nuclei, even after masking Y4 and
      Y5 receptors. Similar results were obtained using 125I-hPYY(3-36) in presence of
      Y2 and Y5 blockers. These results suggest the possible existence of at least one
      additional subtype of NPY receptor sites in the rat brain, with enrichment seen
      in midbrain and brainstem areas involved in the regulation of food intake and
      cardiorespiratory parameters.

PMID- 15947034
TI  - Hypocretin-1 (orexin-A) facilitates inhibitory and diminishes excitatory synaptic
      pathways to cardiac vagal neurons in the nucleus ambiguus.
AB  - Hypocretin-1 is a neuropeptide recently shown to be involved in autonomic
      regulation. Hypocretin-1 is expressed by hypothalamic neurons, which project to
      many regions of the central nervous system, including the nucleus ambiguus. One
      possible site of action of hypocretin-1 could be cardioinhibitory parasympathetic
      vagal neurons within the nucleus ambiguus. This study examines whether hypocretin
      1 modulates inhibitory and excitatory postsynaptic currents in cardiac vagal
      neurons in the rat nucleus ambiguus. GABAergic, glycinergic, and glutamatergic
      activity to cardiac vagal neurons was examined using whole-cell patch-clamp
      recordings in an in vitro brain slice preparation. Hypocretin-1 (1 microM)
      produced a significant increase in the frequency and amplitude of both GABAergic
      and glycinergic inhibitory postsynaptic currents and a significant decrease in
      the frequency of glutamatergic excitatory postsynaptic currents. Application of
      tetrodotoxin (0.5 microM) blocked all of the responses to hypocretin-1,
      indicating the changes in neurotransmission with hypocretin-1 do not occur at
      presynaptic terminals but rather occur at the preceding GABAergic, glycinergic,
      and glutamatergic neurons that project to cardiac vagal neurons. The increase in
      GABAergic and glycinergic inhibitory postsynaptic currents, and the decrease in
      glutamatergic excitatory postsynaptic currents, could be mechanisms by which
      hypocretin-1 affects heart rate and cardiac function.

PMID- 15947035
TI  - Effects of dinucleoside polyphosphates on trabecular meshwork cells and aqueous
      humor outflow facility.
AB  - The most important risk factor for the development of glaucoma is elevated
      intraocular pressure (IOP). Hypotensive drugs decrease IOP, preventing optic
      nerve damage and further vision loss. The balance between aqueous humor (AH)
      production and drainage determines IOP, and problems in AH outflow pathways are
      associated with open-angle glaucoma development. Previous studies have shown the
      presence of diadenosine tetraphosphate (Ap(4)A) and pentaphosphate (Ap(5)A) in
      the AH. Topic application of Ap(4)A to the cornea decreased IOP, whereas Ap(5)A
      increased it. Because dinucleoside polyphosphates stimulate P2Y purinergic
      receptors, we studied their presence in trabecular meshwork (TM) cells.
      Additionally, the effects of diadenosine polyphosphates (Ap(n)As; n = 3-5) and
      Up(4)U (P(1),P(4)-(diuridine 5')-tetraphosphate; INS365) in outflow facility were
      tested. P2Y(1), P2Y(2), and P2Y(4) receptors were detected in TM cells by Western
      blot and immunocytochemistry. In TM cells, Ap(3)A, Ap(4)A, and Ap(5)A induced
      discrete intracellular calcium concentration ([Ca(2+)](i)) mobilizations compared
      with higher and more sustained [Ca(2+)](i) mobilizations after Up(4)U
      application. In bovine ocular anterior segments perfused at constant pressure, 1
      microM Ap(3)A or Ap(4)A increased outflow facility, whereas Up(4)U or Ap(5)A did
      not modify it. 2-MeSADP, a selective P2Y(1) agonist, induced outflow facility
      increases similar to those obtained after Ap(3)A and Ap(4)A, and these were
      prevented by addition of the selective P2Y(1) receptor antagonist MRS-2179 (2'
      deoxy-N(6)-methyladenosine-3',5'-diphosphate). Our results demonstrate that the
      hypotensive effect of Ap(4)A and other dinucleotides is mediated, at least in
      part, by increasing trabecular outflow facility through activation of P2Y(1)
      receptors. The latter would seem to be an interesting target in the development
      of antiglaucomatous drugs to selectively increase AH outflow.

PMID- 15947036
TI  - Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine
      H4 receptor: identification of 4-methylhistamine as the first potent and
      selective H4 receptor agonist.
AB  - The histamine H(4) receptor (H(4)R) is involved in the chemotaxis of leukocytes
      and mast cells to sites of inflammation and is suggested to be a potential drug
      target for asthma and allergy. So far, selective H(4)R agonists have not been
      identified. In the present study, we therefore evaluated the human H(4)R (hH(4)R)
      for its interaction with various known histaminergic ligands. Almost all of the
      tested H(1)R and H(2)R antagonists, including several important therapeutics,
      displaced less than 30% of specific [(3)H]histamine binding to the hH(4)R at
      concentrations up to 10 microM. Most of the tested H(2)R agonists and imidazole
      based H(3)R ligands show micromolar-to-nanomolar range hH(4)R affinity, and these
      ligands exert different intrinsic hH(4)R activities, ranging from full agonists
      to inverse agonists. Interestingly, we identified 4-methylhistamine as a high
      affinity H(4)R ligand (K(i) = 50 nM) that has a >100-fold selectivity for the
      hH(4)R over the other histamine receptor subtypes. Moreover, 4-methylhistamine
      potently activated the hH(4)R (pEC(50) = 7.4 +/- 0.1; alpha = 1), and this
      response was competitively antagonized by the selective H(4)R antagonist JNJ
      7777120 [1-[(5-chloro-1H-indol-2-yl)-carbonyl]-4-methylpiperazine] (pA(2) = 7.8).
      The identification of 4-methylhistamine as a potent H(4)R agonist is of major
      importance for future studies to unravel the physiological roles of the H(4)R.

PMID- 15947037
TI  - 3,4-Methylenedioxymethamphetamine (ecstasy) activates skeletal muscle nicotinic
      acetylcholine receptors.
AB  - Adverse 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) effects are usually
      ascribed to neurotransmitter release in the central nervous system. Since
      clinical features such as fasciculations, muscle cramps, rapidly progressing
      hyperthermia, hyperkalemia, and rhabdomyolysis point to the skeletal muscle as
      additional target, we studied the effects of MDMA on native and cultured skeletal
      muscle. We addressed the question whether malignant hyperthermia (MH)-susceptible
      (MHS) muscle is predisposed to adverse MDMA reactions. Force measurements on
      muscle strips showed that 100 microM MDMA, a concentration close to that
      determined in some MDMA users, regularly enhanced the sensitivity of skeletal
      muscle to caffeine-induced contractures but did not cause contractures on its
      own. The left-shift of the dose-response curve induced by MDMA was greater in
      normal than in MHS muscle. Furthermore, MDMA did not release Ca(2+) from isolated
      sarcoplasmic reticulum vesicles. These findings do not support the view of an MH
      triggering effect on muscle. However, MDMA induced Ca(2+) transients in myotubes
      and increased their acidification rate. Surprisingly, alpha-bungarotoxin, a
      specific antagonist of the nicotinic acetylcholine receptor (nAChR), abolished
      these MDMA effects. The nAChR agonistic action of MDMA was confirmed by patch
      clamp measurements of ion currents on human embryonic kidney cells expressing
      nAChR. We conclude that the neuromuscular junction is a target of MDMA and that
      an activation of nAChR contributes to the muscle-related symptoms of MDMA users.
      The drug may be of particular risk in individuals with abundant extrajunctional
      nAChR such as in generalized denervation or muscle regeneration processes and may
      act on central nAChR.

PMID- 15947038
TI  - Tertiapin-Q blocks recombinant and native large conductance K+ channels in a use
      dependent manner.
AB  - Tertiapin, a short peptide from honey bee venom, has been reported to
      specifically block the inwardly rectifying K(+) (Kir) channels, including G
      protein-coupled inwardly rectifying potassium channel (GIRK) 1+GIRK4
      heteromultimers and ROMK1 homomultimers. In the present study, the effects of a
      stable and functionally similar derivative of tertiapin, tertiapin-Q, were
      examined on recombinant human voltage-dependent Ca(2+)-activated large
      conductance K(+) channel (BK or MaxiK; alpha-subunit or hSlo1 homomultimers) and
      mouse inwardly rectifying GIRK1+GIRK2 (i.e., Kir3.1 and Kir3.2) heteromultimeric
      K(+) channels expressed in Xenopus oocytes and in cultured newborn mouse dorsal
      root ganglion (DRG) neurons. In two-electrode voltage-clamped oocytes, tertiapin
      Q (1-100 nM) inhibited BK-type K(+) channels in a use- and concentration
      dependent manner. We also confirmed the inhibition of recombinant GIRK1+GIRK2
      heteromultimers by tertiapin-Q, which had no effect on endogenous depolarization-
      and hyperpolarization-activated currents sensitive to extracellular divalent
      cations (Ca(2+), Mg(2+), Zn(2+), and Ba(2+)) in defolliculated oocytes. In
      voltage-clamped DRG neurons, tertiapin-Q voltage- and use-dependently inhibited
      outwardly rectifying K(+) currents, but Cs(+)-blocked hyperpolarization-activated
      inward currents including I(H) were insensitive to tertiapin-Q, baclofen, barium,
      and zinc, suggesting absence of functional GIRK channels in the newborn. Under
      current-clamp conditions, tertiapin-Q blocked the action potential after
      hyperpolarization (AHP) and increased action potential duration in DRG neurons.
      Taken together, these results demonstrate that the blocking actions of tertiapin
      Q are not specific to Kir channels and that the blockade of recombinant BK
      channels and native neuronal AHP currents is use-dependent. Inhibition of
      specific types of Kir and voltage-dependent Ca(2+)-activated K(+) channels by
      tertiapin-Q at nanomolar range via different mechanisms may have implications in
      pain physiology and therapy.

PMID- 15947039
TI  - 5-Iodoresiniferatoxin evokes hypothermia in mice and is a partial transient
      receptor potential vanilloid 1 agonist in vitro.
AB  - Transient receptor potential vanilloid 1 (TRPV1) is a capsaicin- and heat-gated
      ion channel required for normal in vivo responses to these painful stimuli.
      However, growing evidence suggests that TRPV1 also participates in
      thermoregulation. Therefore, we examined the effects of a selective TRPV1
      antagonist, 5-iodoresiniferatoxin (I-RTX), on mouse body temperature.
      Surprisingly, s.c. administration of I-RTX (0.1-1 micromol/kg) evoked a
      hypothermic response similar to that evoked by capsaicin (9.8 micromol/kg) in
      naive wild-type mice, but not in mice pretreated with resiniferatoxin, a potent
      TRPV1 agonist, or in naive TRPV1-null mice. In response to I-RTX in vitro, HEK293
      cells expressing rat TRPV1 exhibited increases in intracellular Ca(2+) (biphasic,
      EC(50) = 56.7 nM and 9.9 microM) that depended on Ca(2+) influx and outwardly
      rectifying, capsazepine-sensitive currents that were smaller than those evoked by
      1 microM capsaicin. Thus, I-RTX induces TRPV1-dependent hypothermia in vivo and
      is a partial TRPV1 agonist in vitro.

PMID- 15947040
TI  - Image-guided tumor ablation: standardization of terminology and reporting
      criteria.
AB  - The field of interventional oncology with use of image-guided tumor ablation
      requires standardization of terminology and reporting criteria to facilitate
      effective communication of ideas and appropriate comparison between treatments
      that use different technologies, such as chemical (ethanol or acetic acid)
      ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave,
      ultrasound, and cryoablation. This document provides a framework that will
      hopefully facilitate the clearest communication between investigators and will
      provide the greatest flexibility in comparison between the many new, exciting,
      and emerging technologies. An appropriate vehicle for reporting the various
      aspects of image-guided ablation therapy, including classification of therapies
      and procedure terms, appropriate descriptors of imaging guidance, and terminology
      to define imaging and pathologic findings, are outlined. Methods for
      standardizing the reporting of follow-up findings and complications and other
      important aspects that require attention when reporting clinical results are
      addressed. It is the group's intention that adherence to the recommendations will
      facilitate achievement of the group's main objective: improved precision and
      communication in this field that lead to more accurate comparison of technologies
      and results and, ultimately, to improved patient outcomes. The intent of this
      standardization of terminology is to provide an appropriate vehicle for reporting
      the various aspects of image-guided ablation therapy.

PMID- 15947041
TI  - Portal vein embolization in preparation for major hepatic resection: evolution of
      a new standard of care.
AB  - Portal vein (PV) embolization (PVE) is gaining acceptance in the preoperative
      management of patients selected for major hepatic resection. PVE redirects portal
      blood flow to the intended liver remnant to induce hypertrophy of the nondiseased
      portion of the liver and thereby reduce complications and shorten hospital stays
      after resection. This article reviews the rationale and existing literature on
      PVE, including the mechanisms of liver regeneration, the pathophysiology of PVE,
      the imaging techniques used to measure liver volumes and estimate functional
      hepatic reserve, and the technical aspects of PVE, including approaches and
      embolic agents used. In addition, the indications and contraindications for
      performing PVE in patients with and without chronic liver disease and the
      multidisciplinary approach required for the treatment of these complex cases are
      emphasized.

PMID- 15947042
TI  - Prospective evaluation of higher energy great saphenous vein endovenous laser
      treatment.
AB  - PURPOSE: In this study, the hypothesis that higher energy dose improves
      procedural success without increasing complications was prospectively evaluated
      by performing endovenous laser therapy (ELT) at energies greater than 80 J/cm.
      MATERIALS AND METHODS: One hundred consecutive great saphenous (GSV), anterior
      accessory great saphenous (AAGSV), or posterior accessory great saphenous (PAGSV)
      veins were treated with the intent to deliver an energy dose of greater than 80
      J/cm. Eighty-one patients (64 women, 17 men) were treated. Mean age was 49 years
      (range, 25-77 years; SD, 12 years). Ultrasound (US) and clinical follow-up was
      performed at 1 week, 3, 6, 9, and 12 months until all veins had at least 3 months
      of follow-up. Success was defined as absence of reflux throughout the entire
      treated segment on follow-up US and clinical resolution of symptoms. Incomplete
      vein ablation was defined as US evidence of flow in a segment of a treated vein
      at any point during the follow-up period. RESULTS: One hundred veins were treated
      with an average energy of 95 J/cm (range, 57-145 J/cm; SD, 16 J/cm). Follow-up
      and success at 1 week was 100%. Four veins could not be followed up beyond 1
      week. Of the 96 remaining veins all had 3 months follow-up with an average follow
      up of 9 months (range, 3-13 months; SD, 4 months). There were five failures and
      91 successes for a success rate of 95%. Four of the treatment successes
      demonstrated segmental patency but no reflux on US for a complete vein ablation
      rate of 91%. No major complications occurred. The treatment failures occurred at
      an average energy dose of 98 J/cm. Two of the three failures were AAGSVs, one was
      a GSV ipsilateral to one of the failed AAGSVs, and two were bilateral GSVs
      treated during the same procedure. Average body mass index (BMI) was 30 for the
      successes and 46 for the failures. This difference was statistically significant
      (P = .0009). The mean length of the failed treatments from the saphenofemoral
      junction to their termination into a varicose tributary was 10.9 (range, 8-15 cm;
      SD, 3.7 cm). This was significantly less than the length of the successful
      treatments (P = .000003). CONCLUSION: Higher energy GSV ELT is safe and highly
      successful.

PMID- 15947043
TI  - Hepatic artery stenosis in liver transplant recipients: primary treatment with
      percutaneous transluminal angioplasty.
AB  - PURPOSE: To evaluate the efficacy of hepatic artery percutaneous transluminal
      angioplasty (PTA) in the treatment of hepatic artery stenosis (HAS). MATERIALS
      AND METHODS: A retrospective analysis was performed of all cases of HAS
      documented by angiography from January 1995 to June 2003 at the authors'
      institution. Management was evaluated and long-term patency was documented by
      Doppler ultrasonography. The patency, restenosis, and hepatic artery thrombosis
      (HAT) rates were determined by the Kaplan-Meier method. The technical success of
      hepatic artery PTA was stratified according to the location of the stenoses
      relative to the anastomosis, as well as by the presence of associated hepatic
      arterial kinks. RESULTS: Thrombosis was seen in 65% +/- 13% of untreated HAS
      cases within 6 months. Stenotic lesions without associated arterial kinks had an
      improved technical success rate and a reduced complication rate of 94% and 10%,
      respectively, compared with lesions with associated hepatic arterial kinks
      treated with hepatic artery PTA (14% and 29%, respectively). The 1-year primary
      and primary assisted patency rates of hepatic artery PTA for all lesions were 44%
      +/- 12% and 60% +/- 11%, respectively, and were 65% +/- 10% and 80% +/- 8%,
      respectively, for lesions not associated with hepatic arterial kinks. The 1-year
      HAT rate and restenosis rate after hepatic artery PTA were 19% +/- 10% and 32% +/
      11%, respectively. The 1-year primary assisted patency rate for hepatic artery
      PTA with repeat PTA performed for restenosed lesions and surgical
      revascularization performed for failed PTA was 74% +/- 10%. CONCLUSIONS:
      Untreated HAS carries a high morbidity rate. Hepatic artery PTA can play a large
      role in the management of HAS by reducing the HAT rate more than threefold. With
      appropriate lesion selection, hepatic artery PTA will have better patency rates
      than those associated with hepatic artery stent placement.

PMID- 15947044
TI  - Renal blood flow measurements with use of phase-contrast magnetic resonance
      imaging: normal values and reproducibility.
AB  - PURPOSE: To assess the validity and the direct, short-term, and long-term
      reproducibility of renal blood flow (RBF) measurements with phase-contrast (PC)
      magnetic resonance (MR) imaging. MATERIALS AND METHODS: In 20 healthy volunteers,
      RBF measurements were repeated with and without repositioning. Internal validity
      was assessed by comparing the total RBF with the difference in aortic flow above
      and below the renal arteries. In 19 healthy volunteers, RBF measurements were
      performed at two different occasions. In 40 healthy volunteers, RBF measurements
      were performed to assess normal values as a function of age. Analyses were
      performed according to Bland and Altman. RESULTS: The technical success rate
      ranged from 78% to 85%. Total RBF and the difference in aortic flow rates showed
      good agreement (Pearson correlation coefficient, 0.72; P = .002). Directly
      repeated measurements had a mean difference of 54 mL/min in total RBF with a
      coefficient of variation (CV) of 17%. For repeated measurements with
      repositioning, the mean difference in total RBF was 74 mL/min (CV, 23%). Repeated
      measurements on different occasions showed a CV of 20%. The mean total RBF of the
      40 healthy volunteers was 838 mL/min +/- 244 (SD). CONCLUSIONS: RBF measurement
      with PC MR has a success rate greater than 75%. The demonstrated internal
      reliability of this method and fair reproducibility of the flow parameters is
      crucial for further studies of the renal artery with MR imaging.

PMID- 15947045
TI  - Stents in common iliac vein obstruction with acute ipsilateral deep venous
      thrombosis: early and late results.
AB  - PURPOSE: To evaluate, by imaging and clinical follow-up, the effectiveness and
      long-term results of stent placement in cases of common iliac vein obstruction
      associated with ipsilateral deep vein thrombosis (DVT). MATERIALS AND METHODS:
      Retrospective analysis of 22 patients (13 women, nine men; median age, 58 years)
      with common iliac vein obstruction with ipsilateral DVT was performed for this
      study. All patients presented with leg edema or pain and were treated with
      catheter-directed thrombolysis (1,000-2,000 U urokinase per kg body weight per
      hour; n = 19), aspiration thrombectomy (n = 21), or angioplasty (n = 14) followed
      by stent placement (n = 22) via an ipsilateral popliteal vein approach (right, n
      = 2; left, n = 20) under ultrasonographic (US) guidance. Patients were then
      followed by duplex US, and patency rates were determined by Kaplan-Meier survival
      analysis. RESULTS: The mean procedure time was 15 hours (range, 1-23 hours) and
      the mean urokinase dose was 1,980,000 U (range, 600,000-3,600,000 U) before the
      implantation of 27 stents. Three patients did not receive urokinase. The
      technical success rate was 96% (26 of 27 stents) and the clinical success rate
      was 95% (21 of 22 patients). The causes of common iliac vein obstruction were May
      Thurner syndrome (n = 16), pelvic mass (n = 2), and unknown (n = 4). The early
      complications included upward stent migration in one patient and a spinal
      epidural hematoma in another. The late complication was partial stent
      obstruction, which was successfully treated by thrombolysis and angioplasty in
      one patient. Follow-up lasted 1-41 months (mean, 21.4 months). Overall, the 1
      year and 2-year primary patency rates were both 95% and the 1-year and 2-year
      secondary patency rates were both 100%. CONCLUSION: Directed catheter
      thrombolysis and aspiration of DVT are relatively safe, and the use of stents
      improves patency results in cases of common iliac vein obstruction.

PMID- 15947046
TI  - Hybrid endograft for one-step treatment of multisegment disease of the thoracic
      aorta.
AB  - PURPOSE: At present, a two-step surgical approach is necessary to treat patients
      with coexistent pathologic conditions involving the proximal and descending
      thoracic aorta. A hybrid endograft is described here that enables such treatment
      during a single operation. MATERIALS AND METHODS: The Chavan-Haverich endograft
      consists of a Dacron vascular prosthesis with stainless-steel stents affixed at
      its distal end. After approval by the institutional review board, the endograft
      was prospectively implanted in 22 patients with multisegment thoracic aortic
      disease (13 men, nine women; median age, 64 years). Eleven patients had type A
      dissections (one acute, 10 chronic), four had a chronic type B dissection, and
      seven had atherosclerotic aneurysms of the ascending aorta or aortic arch as well
      as of the descending aorta. Of these patients, 11 additionally required aortic
      valve replacement or coronary artery bypass grafting. Via median sternotomy, the
      aortic arch was opened in circulatory arrest. After antegrade deployment of the
      stent-containing portion in the descending aorta, the proximal non-stent
      containing endograft was used to reconstruct the aortic arch. Median follow-up
      was 14 months. RESULTS: Endograft implantation was successful in all but one
      patient. Complications included neurologic deficits that were transient in one
      case and lasting in two, two cases of vocal cord paralysis, and one death. In all
      patients with atherosclerotic aneurysms who received the endograft (six of
      seven), aneurysm thrombosis was noted at follow-up. In aortic dissections,
      partial or complete false-lumen thrombosis to the level of the stents occurred in
      all patients. None of the patients showed a progressive widening of the
      descending aorta. CONCLUSION: The Chavan-Haverich endograft enables one-step
      treatment of multisegment pathologic conditions affecting the thoracic aorta that
      otherwise would require two or more operations.

PMID- 15947047
TI  - Percutaneous treatment of hydatid liver cysts in children as a primary treatment:
      long-term results.
AB  - PURPOSE: To evaluate the effectiveness and long-term results of percutaneous
      treatment for hydatid liver cysts in pediatric patients. MATERIALS AND METHODS:
      Thirty-four pediatric patients (15 male, 19 female; ages 4-17 years; mean age,
      9.4 years) with 51 hydatid liver cysts underwent ultrasound (US)-guided
      percutaneous treatment with albendazole prophylaxis. There were 15 type II
      lesions with membrane detachment and 36 type I lesions resembling simple hepatic
      cysts with pure anechogenic content or small echogenic reflections and a regular
      well-delineated wall. The method of US-guided puncture, aspiration, injection of
      hypertonic saline solution, and reaspiration was preferred for 21 lesions. For
      the remaining 30 larger cysts, the intervention was performed with the same
      percutaneous technique but followed by catheterization, drainage, control
      cystography, and sclerotherapy with ethanol. During follow-up, US examinations
      were performed at 1, 3, 6, and 12 months for the first year and yearly
      thereafter. RESULTS: Percutaneous treatment of hepatic hydatid disease was
      successful in 33 patients (97.1%). During follow-up, US findings in the lesions
      changed significantly; at year 1, the inner content of the lesions became
      heterogeneous with a semisolid appearance, and the mean reduction in volume was
      81.4%. At 2-year follow-up, most hydatid cysts had become solid in nature and the
      reduction in volume reached 65%-99% (mean, 85.1%). There were no recurrences or
      additional lesions after the follow-up of 1-6 years (mean, 3.1 years). Average
      hospital stay for the whole group in this study was 3.5 days. CONCLUSIONS: The
      long-term results of percutaneous liver hydatid cyst treatment in children are in
      accordance with the results in adults. Percutaneous treatment of uncomplicated
      type I and type II liver hydatid cysts in pediatric patients is an efficient and
      safe treatment with short hospitalization.

PMID- 15947048
TI  - Effect of stabilized iodized oil emulsion on experimentally induced
      hepatocellular carcinoma in rats.
AB  - PURPOSE: Previous studies have shown that the use of Lipiodol UltraFluid (LUF)
      emulsified with water leads to an increase in the tumoral uptake of iodine I 131
      labeled LUF and reduced pulmonary uptake. Although emulsions containing LUF are
      currently used for chemoembolization of hepatocellular carcinomas (HCCs), this
      approach is impossible with intraarterial radiation therapy (RT) because of the
      problems of radiation protection linked to instability of the emulsions. The aims
      of this study were to develop stabilized emulsions of radiolabeled LUF of
      different particle sizes and viscosities and to study its biodistribution in rats
      with HCC. MATERIALS AND METHODS: An emulsifier made of polyethylene glycol and
      hydrogenated castor oil was used to stabilize emulsions containing water and
      technetium Tc 99m-labeled Super Six Sulfur LUF. The various emulsions were
      injected in the hepatic arteries of rats with HCC. Twenty-four hours after
      injection, the rats were killed and the liver, tumor, and lungs were removed to
      perform ex-vivo gamma-counting to quantify tumoral, hepatic, and pulmonary
      uptake. RESULTS: Emulsions of oil in water and water in oil of different
      viscosities (0.68-1.06 Pa.S) and particle size distributions (21-45 mum) were
      prepared and kept stable for more than 24 hours. Whatever the type of emulsion,
      the observed effect on tumoral uptake was the opposite of that expected. Indeed,
      a decrease in tumoral activity was observed (P < .05 in three of five cases) and
      a tendency toward increased pulmonary activity was observed (P < .05 in two of
      five cases) rather than any significant decrease. CONCLUSIONS: This study made it
      possible to develop emulsions of radiolabeled iodized oil that remain stable for
      more than 24 hours. However, studies of biodistribution in rats with HCC failed
      to demonstrate any improvement in tumoral targeting, but rather showed a decrease
      in tumoral uptake that renders this approach impractical for intraarterial
      radiolabeled iodized oil RT as well as for intraarterial iodized oil
      chemoembolization. These results may possibly be explained by the use of an
      emulsifier containing lipophilic and hydrophilic components that modify the
      properties of LUF.

PMID- 15947049
TI  - Extension of radiofrequency ablation of the liver by transcatheter arterial
      embolization with iodized oil and gelatin sponge: results in a pig model.
AB  - PURPOSE: To determine whether transcatheter arterial embolization (TAE) with
      iodized oil and gelatin sponge particles can be used to expand radiofrequency
      (RF)-induced coagulation necrosis, the morphology and histologic characteristics
      of ablation lesions were evaluated in the normal pig liver after three different
      TAE procedures. MATERIALS AND METHODS: Ten consecutive animals with 33 ablation
      lesions produced with an RF ablation system were randomly assigned to one of
      three treatment groups and a control group: a group treated with TAE with iodized
      oil, a group treated with TAE with gelatin sponge, a group treated with TAE with
      iodized oil and gelatin sponge, and a control group in which TAE was not
      performed. After the completion of ablation, the lesions were excised for gross
      and histologic examination. RESULTS: The longest and shortest diameters of
      ablation lesions were greatest in the group treated with TAE with iodized oil and
      gelatin sponge, followed by the groups treated with TAE with gelatin sponge and
      TAE with iodized oil (P < .05 vs controls, respectively). The hemorrhagic rim was
      also widest in the group treated with TAE with iodized oil and gelatin sponge (P
      < .05 vs controls), and it spread toward the liver periphery like a segmental
      hemorrhagic area adjacent to the ablation lesion. Histochemical staining for
      lactate dehydrogenase, maleate dehydrogenase, and nicotinamide adenine
      dinucleotide diaphorase showed what appeared to be 100% cellular destruction in
      all the ablation lesions and their hemorrhagic rims. CONCLUSION: RF ablation
      combined with TAE with iodized oil and gelatin sponge induces the greatest area
      of coagulation necrosis accompanied by peripherally spreading segmental necrosis
      in normal pig liver tissue.

PMID- 15947050
TI  - Embolization of type 2 endoleaks after endovascular repair of abdominal aortic
      aneurysms with use of cyanoacrylate with or without coils.
AB  - Translumbar embolization was used to treat 11 type 2 endoleaks in nine patients
      with the liquid embolic agent n-butyl cyanoacrylate (NBCA). Nine of the
      embolizations were performed with a combination of stainless-steel coils and
      NBCAJ and the other two were performed with NBCA alone. There was complete
      occlusion on initial computed tomographic (CT) angiography in six of nine
      patients (66%), including the two cases treated with NBCA alone. Persistent
      endoleak on initial CT angiography occurred in three of nine patients (33%). Two
      of these patients underwent successful repeated embolization with NBCA. Aneurysm
      size remained unchanged in four patients (44%), decreased in four patients (44%),
      and increased in one patient (11%). No complications occurred. Initial results
      with the use of NBCA for endoleak embolization are encouraging.

PMID- 15947051
TI  - Temporary spontaneous thrombosis of a splenic artery pseudoaneurysm in chronic
      pancreatitis during intravenous octreotide administration.
AB  - Splenic artery pseudoaneurysm is a well-known and potentially life-threatening
      complication of pancreatitis for which immediate endovascular or surgical
      treatment is indicated. An unusual case of spontaneous thrombosis of a splenic
      artery pseudoaneurysm with associated partial splenic infarction was encountered
      in the setting of chronic pancreatitis during intravenous octreotide
      administration, with recanalization 9 months later.

PMID- 15947052
TI  - Temporary endovascular control of a bleeding aortoenteric fistula by
      transcatheter coil embolization.
AB  - A 67-year-old man presented with gastrointestinal bleeding resulting from a
      fistula between the aortic stump and the fourth part of the duodenum 14 months
      after an axillobifemoral bypass, graft excision, and aortic stump closure for
      aortic graft infection. The patient initially refused any attempt at definitive
      surgical treatment so coil embolization of the aortic stump was performed via a
      brachial approach. Coil embolization may be a useful adjunct in the management of
      such difficult problems. This approach may buy time and allow careful planning of
      a definitive treatment or may serve as a palliative procedure in inoperable
      patients.

PMID- 15947053
TI  - Transjugular intrahepatic portosystemic shunt in a living donor left lateral
      segment liver transplant recipient: technical considerations.
AB  - The technical aspects of placing transjugular intrahepatic portosystemic shunts
      (TIPS) in liver transplant recipients with full allografts have well been
      described. In the era of live related hepatic donors, and the growing population
      of their recipients, it is likely that TIPS shunts will be placed in failing
      transplant lobes/segments. Growing allografts that are initially undersized can
      have an unconventional orientation of the hepatic and portal veins, which may
      also change with remodeling and rotation of the graft during their growth. The
      authors review the technical differences for TIPS procedures in transplants,
      particularly split grafts. They describe a technically successful TIPS procedure
      in an undersized and remodeled left lateral segment liver recipient and the
      additional difficulty this may pose.

PMID- 15947054
TI  - Ultrasound-guided endovenous diode laser in the treatment of congenital venous
      malformations: preliminary experience.
AB  - The authors present their experience in treating congenital venous malformations
      with ultrasound (US)-guided endovenous diode laser. Six patients underwent
      treatment of eight venous malformations for complaints including pain, activity
      limitation, or cosmetic defect. At a mean follow-up interval of 14.5 months, all
      had either resolution of (five patients) or marked decrease in (one patient)
      pain, allowing them to resume previously limited activities. There were no
      instances of nerve damage or skin necrosis. One patient had a self-limited
      mucosal tongue base ulcer. In this small series of patients, endovenous laser
      treatment of venous malformations was effective during short-term follow-up.

PMID- 15947055
TI  - Acetic acid sclerotherapy for treatment of a biliary leak from an isolated bile
      duct after hepatic surgery.
AB  - Bile duct leakage from the main biliary tree is not uncommon after hepatic
      surgery. In this case, successful percutaneous treatment was performed for bile
      leakage from an isolated bile duct after left hemihepatectomy in a 48-year-old
      woman who underwent surgery for biliary cystadenocarcinoma and developed a biloma
      at the left subphrenic space. Diagnostic procedures revealed that the right
      posterior segmental bile duct drained aberrantly into the left bile duct, which
      remained undrained after resection and led to biloma formation. Ablation of the
      isolated bile duct was performed with acetic acid, resulting in avoidance of
      repeated operation and other complications.

PMID- 15947056
TI  - Percutaneous CT-guided cementoplasty for stabilization of a femoral neck lesion.

PMID- 15947057
TI  - Functional dissociation of amygdala-modulated arousal and cognitive appraisal, in
      Turner syndrome.
AB  - The amygdala is preferentially activated by facial expressions of fear. Right and
      left amygdala are hypothesized to play distinct, but complementary, roles that
      influence somatic and cognitive responses to facial expressions. Right amygdala
      activation is linked to autonomic arousal, and thus indirectly influences left
      hemisphere cognitive processing centres. Left amygdala activation is more closely
      associated with cognitive processing and differentiation of facial emotions. A
      double-dissociation between the functions of left and right amygdala is implied
      by lesion studies but supportive evidence is inconsistent, partly because
      patients with structural anteromedial temporal anomalies have experienced
      variable surgical procedures. A functional dissociation can be demonstrated
      between arousal and the cognitive appraisal of fearful faces in the condition of
      X-monosomy or Turner syndrome. Previous research found Turner syndrome women of
      normal verbal intelligence are seriously impaired in their ability cognitively to
      differentiate fearful from other facial expressions but they acquire fear
      conditioning normally, with enhanced autonomic responses. These findings
      supported the dissociation hypothesis, which was formally tested in a study of 12
      X-monosomic and 12 control females who participated in functional magnetic
      resonance imaging during which simultaneous skin conductance recordings were
      acquired. Faces depicting fear or neutral emotions were presented to both case
      and control subjects in random order. Arousal to (fearful-neutral) faces was
      associated with transiently increased skin conductance responses and bilateral
      amygdala activation in both groups, but X-monosomic females had proportionately
      greater--and more persistent--right amygdala activation than controls. In both
      groups, cognitive accuracy correlated positively with differential activity of
      left fusiform gyrus. There was a significant correlation between the left
      fusiform and left medial amygdala activation only in normal females, and only in
      them did differential SCRs (to fearful-neutral faces) correlate positively with
      left fusiform responses. Arousal and cognitive appraisal functions of the
      amygdala can thus be functionally dissociated. X-monosomy selectively impairs
      explicit recognition of fearful faces in the presence of normal or enhanced
      autonomic reactivity, and is associated with a functional dissociation of
      activity in left amygdala and left fusiform gyrus. These findings imply X-linked
      genes are essential for binding somatic responses to the cognitive appraisal of
      emotional stimuli.

PMID- 15947058
TI  - Altered motor nerve excitability in end-stage kidney disease.
AB  - Although multiple toxins have been implicated in the development of uraemic
      neuropathy, no causative agent has been identified. In the present study, the
      excitability properties of lower limb motor nerves in patients with end-stage
      kidney disease treated with haemodialysis were measured before, during and after
      a standard 5 h haemodialysis session, in an attempt to explore the
      pathophysiology of uraemic neuropathy. Compound muscle action potentials were
      recorded from tibialis anterior and extensor digitorum brevis, following
      stimulation of the common peroneal nerve in 14 patients. Measures of excitability
      were assessed in relation to changes in serum levels of potential neurotoxins,
      including potassium, calcium, urea, uric acid, parathyroid hormone and beta-2
      microglobulin. Before dialysis, measures of nerve excitability were significantly
      abnormal in the patient group for axons innervating tibialis anterior and
      extensor digitorum brevis, consistent with axonal depolarization: refractoriness
      was increased and superexcitability and depolarizing threshold electrotonus were
      reduced. Pre-dialysis excitability abnormalities were strongly correlated with
      serum K+. Correlation was also noted between the severity of symptoms and
      excitability abnormalities. Haemodialysis normalized the majority of nerve
      excitability parameters. In conclusion, lower limb motor axons in uraemic
      patients are depolarized before dialysis. The correlation between serum K+ and
      excitability measures indicates that hyperkalaemia is primarily responsible for
      uraemic depolarization, and a likely contributing factor to the development of
      neuropathy.

PMID- 15947059
TI  - Cerebral small-vessel disease and decline in information processing speed,
      executive function and memory.
AB  - Cerebral small-vessel disease is common in older people and may contribute to the
      development of dementia. The objective of the present study was to evaluate the
      relationship between measures of cerebral small-vessel disease on MRI and the
      rate of decline in specific cognitive domains in participants from the
      prospective, population-based Rotterdam Scan Study. Participants were 60-90 years
      of age and free from dementia at baseline in 1995-1996. White matter lesions
      (WML), cerebral infarcts and generalized brain atrophy were assessed on the
      baseline MRI. We performed neuropsychological testing at baseline and repeatedly
      in 1999-2000 and in 2001-2003. We used random-effects models for repeated
      measures to examine the association between quantitative MRI measures and rate of
      decline in measures of global cognitive function, information processing speed,
      executive function and memory. There were a total of 2266 assessments for the 832
      participants in the study, with an average time from the initial to last
      assessment of 5.2 years. Increasing severity of periventricular WML and
      generalized brain atrophy and the presence of brain infarcts on MRI were
      associated with a steeper decline in cognitive function. These structural brain
      changes were specifically associated with decline in information processing speed
      and executive function. The associations between MRI measures of cerebral small
      vessel disease and cognitive decline did not change after additional adjustment
      for vascular risk factors or depressed mood. After exclusion of participants with
      an incident stroke, some of the associations of periventricular WML, brain
      infarcts and generalized brain atrophy with measures of information processing
      speed and executive function were no longer significant. This may indicate that
      stroke plays an intermediate role in the relationship between cerebral small
      vessel disease and cognitive decline. Our results suggest that in older people
      cerebral small-vessel disease may contribute to cognitive decline by affecting
      information processing speed and executive function.

PMID- 15947060
TI  - Temperature-dependent double spikes in C-nociceptors of neuropathic pain
      patients.
AB  - Five patients with small-fibre neuropathy characterized by temperature-dependent
      spontaneous pain, hyperalgesia/allodynia and signs of neurogenic inflammation
      were studied clinically and thermographically, and by microneurography.
      Thermography revealed hyperthermia confined to painful and hyperalgesic skin of
      distal extremities, in absence of sympathetic vasomotor denervation. Quantitative
      sensory testing documented either reduced thresholds or increased suprathreshold
      magnitude for heat pain. Microneurography identified 13 primary cutaneous C
      nociceptors generating abnormal impulses in response to electrical stimuli and,
      in one patient, nociceptors firing spontaneously. All five patients showed
      examples of double spikes, in which a single brief electrical stimulus
      occasionally or regularly evoked two impulses. In one case, a second impulse
      occurred at one of three different delays. In all five patients, warming of the
      skin increased the probability of a second impulse occurring. Impulse doubling
      has previously been reported as occurring rarely in normal subjects and is
      attributable to unfiltering of multiple orthodromic impulses due to
      unidirectional conduction failure at branch points. A higher incidence of double
      firing in neuropathic pain patients is probably due to a reduced safety factor
      for conduction in the terminal arborizations of their C-nociceptors. These
      observations show that unidirectional conduction block provides a peripheral
      mechanism of temperature-dependent nociceptor hyperactivity in small-fibre
      neuropathy that may contribute to hyperalgesia.

PMID- 15947061
TI  - Thalamic infarctions cause side-specific suppression of vestibular cortex
      activations.
AB  - H2O15-PET was performed during caloric vestibular stimulation of the right and
      left external ears in eight right-handed patients with acute unilateral
      infarctions or haemorrhages of the posterolateral thalamus (four right, four
      left). The posterolateral thalamus is the relay station for ipsi- and
      contralateral ascending vestibular input to the multiple multisensory vestibular
      cortex areas. The aim of this study was to evaluate the differential effects of
      unilateral vestibular thalamic lesions on thalamo-cortical projections, right
      hemispheric dominance and reciprocal inhibitory visual-vestibular interaction, as
      well as perceptual and ocular motor consequences during caloric irrigation. The
      major findings of the group analyses of the patients with right-sided and those
      with left-sided lesions were as follows: (i) activation of the multisensory
      vestibular temporo-parietal cortex was significantly reduced in the hemisphere
      ipsilateral to the thalamic lesion when the ipsilesional or contralesional ear
      was stimulated; (ii) activation of multisensory vestibular cortex areas of the
      hemisphere contralateral to the irrigated ipsilesional ear was also diminished;
      and (iii) the right hemispheric dominance in right-handers described above was
      preserved in those with right and left thalamic lesions. Simultaneous
      deactivations were often restricted to only one hemisphere--the one contralateral
      to the stimulation and contralateral to the vestibular cortex areas activated.
      There was, however, one area in the inferior insula which was also activated by
      either right or left ear stimulation in the hemisphere ipsilateral to the lesion.
      This supports the assumption that there is a bilateral direct ascending
      vestibular projection from the vestibular nuclei to the inferior part of the
      insula, which bypasses the posterolateral thalamus and is stronger in the right
      hemisphere. The cortical asymmetry of the pattern of activation during horizontal
      semicircular canal stimulation by calorics was not associated with a significant
      direction-specific asymmetry of caloric nystagmus or perceived body motion. Thus,
      the data demonstrate the functional importance of the posterolateral thalamus as
      a unique relay station for vestibular input to the cortex, of the dominance of
      the right hemisphere in right-handedness, and of ipsilateral ascending pathways.
      Furthermore, the normal interaction between the two sensory systems--the
      vestibular and the visual--appears to be impaired.

PMID- 15947062
TI  - Megadolichobasilar anomaly with thrombosis in a family with Fabry's disease and a
      novel mutation in the alpha-galactosidase A gene.
AB  - Fabry's disease is an X-linked lysosomal storage disorder. alpha-Galactosidase
      deficiency leads to accumulation of globotriaosylceramide mainly in endothelial
      and smooth muscle cells. Cerebrovascular symptoms with predominant affection of
      the vertebrobasilar circulation are one of the major sources of morbidity in
      Fabry's disease. We present a Hungarian family with Fabry's disease caused by a
      new mutation in the alpha-galactosidase A gene (GLA), and describe a variant
      expression of the disease. Megadolichobasilar anomaly was diagnosed in two male
      patients in the family who died of thrombosis. In another female patient who had
      suffered from disturbance of the vertebrobasilar circulation, a strongly dilated
      basilar artery without thrombosis was found at autopsy. Another three family
      members had basilar strokes and large and elongated basilar arteries on MRI.
      Genetic analysis disclosed a c.47T-->C missense mutation resulting in L16P in the
      amino acid sequence of the alpha-galactosidase protein. This report suggests that
      megadolichobasilar anomaly is potentially life-threatening, and that L16P is a
      disease-causing mutation in patients with Fabry's disease. Early enzyme
      replacement therapy may prevent the development of these irreversible
      cerebrovascular complications.

PMID- 15947063
TI  - The fragile X tremor ataxia syndrome in the differential diagnosis of multiple
      system atrophy: data from the EMSA Study Group.
AB  - The recent identification of fragile X-associated tremor ataxia syndrome (FXTAS)
      associated with premutations in the FMR1 gene and the possibility of clinical
      overlap with multiple system atrophy (MSA) has raised important questions, such
      as whether genetic testing for FXTAS should be performed routinely in MSA and
      whether positive cases might affect the specificity of current MSA diagnostic
      criteria. We genotyped 507 patients with clinically diagnosed or pathologically
      proven MSA for FMR1 repeat length. Among the 426 clinically diagnosed cases, we
      identified four patients carrying FMR1 premutations (0.94%). Within the subgroup
      of patients with probable MSA-C, three of 76 patients (3.95%) carried
      premutations. We identified no premutation carriers among 81 patients with
      pathologically proven MSA and only one carrier among 622 controls (0.16%). Our
      results suggest that, with proper application of current diagnostic criteria,
      FXTAS is very unlikely to be confused with MSA. However, slowly progressive
      disease or predominant tremor are useful red flags and should prompt the
      consideration of FXTAS. On the basis of our data, the EMSA Study Group does not
      recommend routine FMR1 genotyping in typical MSA patients.

PMID- 15947064
TI  - Myotilinopathy: refining the clinical and myopathological phenotype.
AB  - Mutations in myotilin gene (MYOT) have been associated with variable syndromes
      including limb girdle muscular dystrophy type 1A (LGMD1A) and a subgroup of
      myofibrillar myopathy (MFM/MYOT). We studied six Spanish patients from three
      unrelated kindreds and seven patients without family history. Three previously
      reported and two novel disease-associated MYOT mutations were identified in this
      group of patients. The disease is characterized by the onset at the age of 42-77
      years with muscle weakness initially in distal or proximal leg muscles,
      eventually spreading to other muscle groups of the lower and upper extremities.
      Associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy
      are present in a fraction of patients. Myopathological features of focal
      myofibrillar destruction resulting in intracytoplasmic deposits, strongly
      immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally
      located non-rimmed vacuoles and streaming Z-lines, were observed in each patient
      studied. The Spanish cohort, the largest group of patients studied so far, shares
      phenotypic features with both LGMD1A and MFM/MYOT variants thus establishing a
      continuum of phenotypic manifestations characteristic of myotilinopathy, an
      emerging neuromuscular disorder.

PMID- 15947065
TI  - Motor reorganization in asymptomatic carriers of a single mutant Parkin allele: a
      human model for presymptomatic parkinsonism.
AB  - Mutations in the Parkin gene are the most common known single cause of early
      onset parkinsonism. It has been shown that asymptomatic carriers with a single
      mutant allele have latent presynaptic dopaminergic dysfunction in the striatum.
      Here we used functional MRI to map movement-related neuronal activity during
      internally selected or externally determined finger movements in 12 asymptomatic
      carriers of a Parkin mutation and 12 healthy non-carriers. Mean response times
      were 63 ms shorter during internally selected movements than during externally
      guided movements (P = 0.003). There were no differences in mean response times
      between groups (P > 0.2). Compared with externally determined movements, the
      internal selection of movements led to a stronger activation of rostral motor
      areas, including the rostral cingulate motor area (rCMA), rostral supplementary
      motor area, medial and dorsolateral prefrontal cortices. The genotype had a
      significant impact on movement-related activation patterns. Asymptomatic carriers
      showed a stronger increase in movement-related activity in the right rCMA and
      left dorsal premotor cortex, but only if movements relied on internal cues. In
      addition, synaptic activity in the rCMA had a stronger influence on activity in
      the basal ganglia in the context of internally selected movements in asymptomatic
      carriers relative to non-carriers. We infer that this reorganization of
      striatocortical motor loops reflects a compensatory effort to overcome latent
      nigrostriatal dysfunction.

PMID- 15947066
TI  - Lessons from the bone marrow: how malignant glioma cells attract adult
      haematopoietic progenitor cells.
AB  - Stem and progenitor cells (PCs) of various lineages have become attractive
      vehicles to improve therapeutic gene delivery to cancers, notably glioblastoma.
      Here we report that adult human and murine haematopoietic PCs display a tropism
      for intracerebral gliomas but not for normal brain tissue in mice. Organotypic
      hippocampal slice culture and spheroid confrontation assays confirm a directed PC
      migration towards glioma cells ex vivo and in vitro. RNA interference-mediated
      disruption of transforming growth factor beta (TGF-beta) synthesis by the glioma
      cells strongly inhibits PC migration. We delineate a CXC chemokine ligand (CXCL)
      12-dependent pathway of TGF-beta-induced PC migration that is facilitated by MMP
      9-mediated stem cell factor cleavage in vitro. Moreover, neutralizing antibodies
      to CXCL12 strongly reduce PC homing to experimental gliomas in vivo. Thus, we
      define here the molecular mechanism underlying the glioma tropism of the probably
      most easily accessible PC population suitable for cancer therapy, that is, adult
      haematopoietic PC.

PMID- 15947067
TI  - Epithelial Ca(2+) channel expression and Ca(2+) uptake in developing zebrafish.
AB  - The purpose of the present work was to study the possible role of the epithelial
      Ca(2+) channel (ECaC) in the Ca(2+) uptake mechanism in developing zebrafish
      (Danio rerio). With rapid amplification of cDNA ends, full-length cDNA encoding
      the ECaC of zebrafish (zECaC) was cloned and sequenced. The cloned zECaC was
      2,578 bp in length and encoded a protein of 709 amino acids that showed up to 73%
      identity with previously described vertebrate ECaCs. The zECaC was found to be
      expressed in all tissues examined and began to be expressed in the skin covering
      the yolk sac of embryos at 24 h postfertilization (hpf). zECaC-expressing cells
      expanded to cover the skin of the entire yolk sac after embryonic development and
      began to occur in the gill filaments at 96 hpf, and thereafter zECaC-expressing
      cells rapidly increased in both gills and yolk sac skin. Corresponding to ECaC
      expression profile, the Ca(2+) influx and content began to increase at 36-72 hpf.
      Incubating zebrafish embryos in low-Ca(2+) (0.02 mM) freshwater caused
      upregulation of the whole body Ca(2+) influx and zECaC expression in both gills
      and skin. Colocalization of zECaC mRNA and the Na(+)-K(+)-ATPase alpha-subunit (a
      marker for mitochondria-rich cells) indicated that only a portion of the
      mitochondria-rich cells expressed zECaC mRNA. These results suggest that the
      zECaC plays a key role in Ca(2+) absorption in developing zebrafish.

PMID- 15947068
TI  - Renal ischemia induces an increase in nitric oxide levels from tissue stores.
AB  - Tissue nitric oxide (NO) levels increase dramatically during ischemia, an effect
      that has been shown to be partially independent from NO synthases. Because NO is
      stored in tissues as S-nitrosothiols and because these compounds could release NO
      during ischemia, we evaluated the effects of buthionine sulfoximine (BSO; an
      intracellular glutathione depletor), light stimulation (which releases NO,
      decomposing S-nitrosothiols), and N-acetyl-L-cysteine (a sulfhydryl group donor
      that repletes S-nitrosothiols stores) on the changes in outer medullary NO
      concentration produced during 45 min of renal artery occlusion in anesthetized
      rats. Renal ischemia increased renal tissue NO concentration (+223%), and this
      effect was maintained along 45 min of renal arterial blockade. After reperfusion,
      NO concentration fell below preischemic values and remained stable for the
      remainder of the experiment. Pretreatment with 10 mg/kg nitro-L-arginine methyl
      ester (L-NAME) decreased significantly basal NO concentration before ischemia,
      but it did not modify the rise in NO levels observed during ischemia. In rats
      pretreated with 4 mmol/kg BSO and L-NAME, ischemia was followed by a transient
      increase in renal NO concentration that fell to preischemic values 20 min before
      reperfusion. A similar response was observed when the kidney was illuminated 40
      min before the ischemia. The coadministration of 10 mg/kg iv N-acetyl-L-cysteine
      with BSO + L-NAME restored the increase in NO levels observed during renal
      ischemia and prevented the depletion of renal thiol groups. These results
      demonstrate that the increase in renal NO concentration observed during ischemia
      originates from thiol-dependent tissue stores.

PMID- 15947069
TI  - Orexin A-induced feeding is augmented by caloric challenge.
AB  - Orexin neurons are stimulated by conditions that are glucoprivic, suggesting that
      orexin signaling may be increased during nutritional duress. We have previously
      shown that injection of orexin A (OxA) into the rostral lateral hypothalamic area
      (rLHa) robustly and dose-dependently increases feeding behavior. Thus we
      hypothesized that exogenous administration of orexin A would induce a greater
      feeding response after acute food deprivation or perceived caloric duress
      achieved through 2-deoxyglucose (2DG) administration. To test our hypothesis,
      male Sprague-Dawley rats implanted with internal guide cannulas directed to the
      rLHa were exposed to varying degrees of food deprivation (0, 3, 12, 24 h) and 2DG
      (200 mg/kg) before intra-rLHa OxA (500 pmol) infusion. We also performed a dose
      response study using graded doses of OxA (0, 31.25, 125, and 500 pmol) in fed and
      24-h fasted rats. OxA administration in conjunction with the highest level of
      prior food deprivation (24 h) resulted in the greatest feeding response (above
      baseline means; 0 h deprivation: 1.9 +/- 0.6; 24 h deprivation: 4.4 +/- 0.8; P =
      0.0034) and showed a dose-dependent enhancement of feeding. Additionally, 2DG
      administration before OxA administration resulted in a significantly higher
      feeding response (above baseline means: 2DG = 1.8 +/- 0.5; OxA = 1.8 +/- 0.4; 2DG
      + OxA = 5.1 +/- 0.6; P < 0.0001). These data support the hypothesis that orexin
      signaling may be important in modulating the feeding network under times of
      nutritional duress.

PMID- 15947071
TI  - Aging reduces responsiveness to BSO- and heat stress-induced perturbations of
      glutathione and antioxidant enzymes.
AB  - Aging alters cellular responses to both heat and oxidative stress. Thiol-mediated
      metabolism of reactive oxygen species (ROS) is believed to be important in aging.
      To begin to determine the role of thiols in aging and heat stress, we depleted
      liver glutathione (GSH) by administering l-buthionine sulfoximine (BSO) in young
      (6 mo) and old (24 mo) Fisher 344 rats before heat stress. Animals were given BSO
      (4 mmol/kg ip) or saline (1 ml ip) 2 h before heat stress and subsequently heated
      to a core temperature of 41 degrees C over a 90-min period. Liver tissue was
      collected before and 0, 30, and 60 min after heat stress. BSO inhibited glutamate
      cysteine ligase (GCL, the rate-limiting enzyme in GSH synthesis) catalytic
      activity and resulted in a decline in liver GSH and GSSG that was more pronounced
      in young compared with old animals. Catalase activity did not change between
      groups until 60 min after heat stress in young BSO-treated rats. Young animals
      experienced a substantial and persistent reduction in Cu,Zn-SOD activity with BSO
      treatment. Mn-SOD activity increased with BSO but declined after heat stress. The
      differences in thiol depletion observed between young and old animals with BSO
      treatment may be indicative of age-related differences in GSH
      compartmentalization that could have an impact on maintenance of redox
      homeostasis and antioxidant balance immediately after a physiologically relevant
      stress. The significant changes in antioxidant enzyme activity after GSH
      depletion suggest that thiol status can influence the regulation of other
      antioxidant enzymes.

PMID- 15947070
TI  - Early antibiotic administration but not antibody therapy directed against IL-6
      improves survival in septic mice predicted to die on basis of high IL-6 levels.
AB  - Elevated interleukin (IL)-6 levels correlate with increased mortality following
      sepsis. IL-6 levels >14,000 pg/ml drawn 6 h after cecal ligation and puncture
      (CLP) are associated with 100% mortality in ND4 mice, even if antibiotic therapy
      is initiated 12 h after septic insult. Our first aim was to see whether earlier
      institution of antibiotic therapy could improve overall survival in septic mice
      and rescue the subset of animals predicted to die on the basis of high IL-6
      levels. Mice (n = 184) were subjected to CLP, had IL-6 levels drawn 6 h later,
      and then were randomized to receive imipenem, a broad spectrum antimicrobial
      agent, beginning 6 or 12 h postoperatively. Overall 1-wk survival improved from
      25.5 to 35.9% with earlier administration of antibiotics (P < 0.05). In mice with
      IL-6 levels >14,000 pg/ml, 25% survived if imipenem was started at 6 h, whereas
      none survived if antibiotics were started later (P < 0.05). On the basis of these
      results, we examined whether targeted antibody therapy could improve survival in
      mice with elevated IL-6 levels. A different cohort of mice (n = 54) had blood
      drawn 6 h after CLP, and then they were randomized to receive either monoclonal
      anti-IL-6 IgG or irrelevant rat IgG. Anti-IL-6 antibody failed to improve either
      overall survival or outcome in mice with IL-6 levels >14,000 pg/ml. These results
      demonstrate that earlier systemic therapy can improve outcome in a subset of mice
      predicted to die in sepsis, but we are unable to demonstrate any benefit in
      similar animals using targeted therapy directed at IL-6.

PMID- 15947073
TI  - Clinical assessment of blood leukocytes, serum cytokines, and serum
      immunoglobulins as responses to sleep deprivation in laboratory rats.
AB  - The specific systems and mechanisms affected by sleep deprivation that may
      perpetuate disease processes in humans still are speculative. In laboratory rats,
      prolonged sleep deprivation induces a state marked by abnormal control over
      indigenous bacteria that results in transient infections of internal tissues and
      eventual lethal septicemia. The present studies investigated changes in blood,
      serum, and bone marrow parameters that may provide diagnostic clues to
      immunopathology. Prolonged sleep deprivation was produced in rats by the disk
      over-water method, a well-established and selective means that does not interfere
      with normal waking behaviors. Measurements included bone and blood differential
      white blood cell counts, multiple serum cytokines and chemokines, several major
      Ig classes and subclasses, and serum endotoxin concentrations. The results
      indicated mild, regenerative neutrophilia in sleep-deprived rats, initially
      accompanied by immature neutrophils and later by monocytosis. The corresponding
      serum cytokine profile revealed an evolving proinflammatory state, particularly
      by high incidence of interleukin-1beta, implicating mononuclear phagocytes and
      resident tissue cells as main intermediary sources. In addition, multiple serum
      Ig classes were increased by sleep deprivation without experimental
      administration of an exogenous antigen. Despite this immune activation, there was
      failure to eradicate invading bacteria and toxins, suggesting competing anti
      inflammatory processes or interference with immune effector functions during
      sleep deprivation. Nearly all of the immune-related events that emerged as
      responses to sleep deprivation have been implicated as etiological or provocative
      factors in other disease processes and may provide means by which sleep
      deprivation as a risk factor in disease may become understood.

PMID- 15947072
TI  - P2X2 and P2X3 receptor expression in postnatal and adult rat urinary bladder and
      lumbosacral spinal cord.
AB  - P2X receptors mediate the effects of ATP in micturition and nociception. During
      postnatal maturation, a spinobulbospinal reflex and voluntary voiding replace
      primitive voiding reflexes. This may involve changes in neuroactive compounds and
      receptors in bladder reflex pathways. We examined P2X2 and P2X3 receptors in
      bladder and spinal cord from postnatal (P0-P36, indicating number of days) and
      adult Wistar rats. Western blot of whole bladders for P2X2 and P2X3 expression
      was performed. Immunostaining for P2X2 and P2X3 receptors in urothelium and
      detrusor smooth muscle whole mounts and spinal cord sections was examined.
      Western blot demonstrated an age-dependent decrease (R(2) = 0.96, P </= 0.005) in
      P2X2 receptor expression in bladder, whereas P2X3 receptor expression in bladder
      peaked (P </= 0.005) during P14-P21. P2X2-immunoreactivity (IR) was present in
      urothelial cells, suburothelial plexus, detrusor smooth muscle, and serosa at
      birth, with staining in urothelial cells and serosa being most predominant. With
      increasing postnatal age, the intensity of P2X2-IR decreased in urothelial cells
      but increased in suburothelial plexus. P2X3-IR increased in urothelial cells and
      suburothelial plexus with postnatal age, whereas staining in detrusor and serosa
      remained relatively constant. At birth, P2X3-IR was present in the dorsal horn,
      lateral collateral pathway, and dorsal commissure. With increasing age, P2X3-IR
      was restricted to superficial dorsal horn and lateral collateral pathway. P2X2-IR
      was present in ependyme cells (S-100-IR) of the central canal as early as P2.
      These studies demonstrate plastic expression of P2X2 and P2X3 receptors in
      bladder and spinal cord during early postnatal development at times coincident
      with appearance of mature voiding patterns.

PMID- 15947074
TI  - P boutons in lamina IX of the rodent spinal cord express high levels of glutamic
      acid decarboxylase-65 and originate from cells in deep medial dorsal horn.
AB  - Presynaptic inhibition of primary muscle spindle (group Ia) afferent terminals in
      motor nuclei of the spinal cord plays an important role in regulating motor
      output and is produced by a population of GABAergic axon terminals known as P
      boutons. Despite extensive investigation, the cells that mediate this control
      have not yet been identified. In this work, we use immunocytochemistry with
      confocal microscopy and EM to demonstrate that P boutons can be distinguished
      from other GABAergic terminals in the ventral horn of rat and mouse spinal cord
      by their high level of the glutamic acid decarboxylase (GAD) 65 isoform of GAD.
      By carrying out retrograde labeling from lamina IX in mice that express green
      fluorescent protein under the control of the GAD65 promoter, we provide evidence
      that the cells of origin of the P boutons are located in the medial part of
      laminae V and VI. Our results suggest that P boutons represent the major output
      of these cells within the ventral horn and are consistent with the view that
      presynaptic inhibition of proprioceptive afferents is mediated by specific
      populations of interneurons. They also provide a means of identifying P boutons
      that will be important in studies of the organization of presynaptic control of
      Ia afferents.

PMID- 15947075
TI  - The turbulent wall jet: a triple-layered structure and incomplete similarity.
AB  - We demonstrate using the high-quality experimental data that turbulent wall jet
      flows consist of two self-similar layers: a top layer and a wall layer, separated
      by a mixing layer where the velocity is close to maximum. The top and wall layers
      are significantly different from each other, and both exhibit incomplete
      similarity, i.e., a strong influence of the width of the slot that had previously
      been neglected.

PMID- 15947076
TI  - A requirement for memory retrieval during and after long-term extinction
      learning.
AB  - Current learning theories are based on the idea that learning is driven by the
      difference between expectations and experience (the delta rule). In extinction,
      one learns that certain expectations no longer apply. Here, we test the potential
      validity of the delta rule by manipulating memory retrieval (and thus
      expectations) during extinction learning. Adrenergic signaling is critical for
      the time-limited retrieval (but not acquisition or consolidation) of contextual
      fear. Using genetic and pharmacologic approaches to manipulate adrenergic
      signaling, we find that long-term extinction requires memory retrieval but not
      conditioned responding. Identical manipulations of the adrenergic system that do
      not affect memory retrieval do not alter extinction. The results provide
      substantial support for the delta rule of learning theory. In addition, the
      timing over which extinction is sensitive to adrenergic manipulation suggests a
      model whereby memory retrieval occurs during, and several hours after, extinction
      learning to consolidate long-term extinction memory.

PMID- 15947077
TI  - Cultural transmission of tool use in bottlenose dolphins.
AB  - In Shark Bay, wild bottlenose dolphins (Tursiops sp.) apparently use marine
      sponges as foraging tools. We demonstrate that genetic and ecological
      explanations for this behavior are inadequate; thus, "sponging" classifies as the
      first case of an existing material culture in a marine mammal species. Using
      mitochondrial DNA analyses, we show that sponging shows an almost exclusive
      vertical social transmission within a single matriline from mother to female
      offspring. Moreover, significant genetic relatedness among all adult spongers at
      the nuclear level indicates very recent coancestry, suggesting that all spongers
      are descendents of one recent "Sponging Eve." Unlike in apes, tool use in this
      population is almost exclusively limited to a single matriline that is part of a
      large albeit open social network of frequently interacting individuals, adding a
      new dimension to charting cultural phenomena among animals.

PMID- 15947078
TI  - Progressive multifocal leukoencephalopathy in a patient treated with natalizumab.
AB  - We describe the clinical course of a patient with multiple sclerosis in whom
      progressive multifocal leukoencephalopathy (PML), an opportunistic viral
      infection of the central nervous system, developed during treatment with
      interferon beta-1a and a selective adhesion-molecule blocker, natalizumab. The
      first PML lesion apparent on magnetic resonance imaging was indistinguishable
      from a multiple sclerosis lesion. Despite treatment with corticosteroids,
      cidofovir, and intravenous immune globulin, PML progressed rapidly, rendering the
      patient quadriparetic, globally aphasic, and minimally responsive. Three months
      after natalizumab therapy was discontinued, changes consistent with an immune
      reconstitution inflammatory syndrome developed. The patient was treated with
      systemic cytarabine, and two months later, his condition had improved.

PMID- 15947079
TI  - Progressive multifocal leukoencephalopathy complicating treatment with
      natalizumab and interferon beta-1a for multiple sclerosis.
AB  - A 46-year-old woman with relapsing-remitting multiple sclerosis died from
      progressive multifocal leukoencephalopathy (PML) after having received 37 doses
      of natalizumab (300 mg every four weeks) as part of a clinical trial of
      natalizumab and interferon beta-1a. PML was diagnosed on the basis of the finding
      of JC viral DNA in cerebrospinal fluid on polymerase-chain-reaction assay and was
      confirmed at autopsy. Nearly every tissue section from bilateral cerebral
      hemispheres contained either macroscopic or microscopic PML lesions. There was
      extensive tissue destruction and cavitation in the left frontoparietal area,
      large numbers of bizarre astrocytes, and inclusion-bearing oligodendrocytes,
      which were positive for JC virus DNA on in situ hybridization.

PMID- 15947080
TI  - Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's
      disease.
AB  - The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn's
      disease treated with natalizumab, a monoclonal antibody against alpha4 integrins,
      was reclassified as JC virus-related progressive multifocal leukoencephalopathy
      (PML). Analysis of frozen serum samples showed that JC virus DNA had appeared in
      the serum three months after the initiation of open-label natalizumab monotherapy
      and two months before the appearance of symptomatic PML. There was staining of
      the brain lesion for polyomavirus. This case report, along with two others,
      suggests that anti-alpha4-integrin therapy can result in JC virus-induced PML.

PMID- 15947081
TI  - Patients at risk.

PMID- 15947082
TI  - Progressive multifocal leukoencephalopathy and natalizumab--unforeseen
      consequences.

PMID- 15947083
TI  - Natalizumab and progressive multifocal leukoencephalopathy.

PMID- 15947084
TI  - Genetic divergence between North American ancestral soybean lines and
      introductions with resistance to soybean cyst nematode revealed by chloroplast
      haplotype.
AB  - Domesticated soybean [Glycine max (L.) Merr.] is a major crop with an established
      ancestral relationship to wild soybean (Glycine soja Sieb. & Zucc.) native to
      Asia. Soybean genetic diversity can be assessed at different levels by
      identification of polymorphic alleles at genetic loci, in either the plastid or
      nuclear genomes. The objective of this study was to evaluate genetic diversity
      based on chloroplast haplotypes for soybean genotypes present in the USDA
      germplasm resource collection. Shared chloroplast haplotypes represent broad
      groups of genetic relatedness. Previous work categorized three-quarters of the
      cultivated soybeans from Asia into a single haplotype group. Our results
      confirmed the close relationship of North American soybean ancestors and G. max
      plant introductions previously identified as representing potential sources of
      soybean genetic variation with the finding that these genotypes belonged to a
      single chloroplast haplotype group. Genetic diversity was identified in soybean
      genotypes determined to have a high density of single nucleotide polymorphisms
      and in a screen of accessions with resistance to soybean cyst nematode.
      Characterization of soybean plant introduction lines into chloroplast haplotype
      group may be an important initial step in evaluating the appropriate use of
      particular soybean genotypes.

PMID- 15947085
TI  - Identification of the receptor scavenging hemopexin-heme complexes.
AB  - Heme released from heme-binding proteins on internal hemorrhage, hemolysis,
      myolysis, or other cell damage is highly toxic due to oxidative and
      proinflammatory effects. Complex formation with hemopexin, the high-affinity heme
      binding protein in plasma and cerebrospinal fluid, dampens these effects and is
      suggested to facilitate cellular heme metabolism. Using a ligand-affinity
      approach, we purified the human hemopexin-heme receptor and identified it as the
      low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed
      in several cell types including macrophages, hepatocytes, neurons, and
      syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed
      that hemopexin-heme complex formation elicits the high receptor affinity. Uptake
      studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells
      and confocal microscopy of the cellular processing of fluorescent hemopexin-heme
      complex established the ability of LRP/CD91 to mediate hemopexin-heme
      internalization resulting in cellular heme uptake and lysosomal hemopexin
      degradation. Uptake of hemopexin-heme complex induced LRP/CD91-dependent heme
      oxygenase 1 mRNA transcription in cultured monocytes. In conclusion, hemopexin
      heme complexes are removed by a receptor-mediated pathway showing striking
      similarities to the CD163-mediated haptoglobin-hemoglobin clearance in
      macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91
      in inflammation.

PMID- 15947086
TI  - Primary cutaneous large B-cell lymphomas: clinicopathologic features,
      classification, and prognostic factors in a large series of patients.
AB  - In the new World Health Organization/European Organization for Research and
      Treatment of Cancer (WHO/EORTC) classification of cutaneous lymphomas, large B
      cell lymphomas (LBCLs) are divided into 3 groups: LBCL, leg-type (LBCLLT);
      follicle center lymphoma, diffuse type (FCLDT); and LBCL, others (LBCLO). We
      studied a large number of primary cutaneous LBCLs to test the validity of the
      classification and to identify prognostic factors for these patients. Ninety
      three cases of primary cutaneous LBCL were analyzed for clinicopathologic
      features, expression of several markers including Bcl-2, Bcl-6, MUM-1, and FOX
      P1, in situ hybridization for Epstein-Barr virus, and molecular analyses of IGH
      gene rearrangement and of Borrelia burgdorferi and human herpesvirus 8 DNA.
      Patients were classified into the following categories: FCLDT, 44 cases; LBCLLT,
      40 cases; and LBCLO, 9 cases. Statistical analyses showed that the LBCLLT and
      FCLDT groups were clearly distinct in terms of clinicopathologic features and
      survival. The LBCLO group had features in between those of LBCLLT and FCLDT. Our
      study shows that accurate morphologic and phenotypic analyses allow us to
      stratify most patients into the prognostically different categories of LBCLLT and
      FCLDT. The definition of a third category of LBCLO requires further studies to
      clarify whether these cases indeed show distinct clinicopathologic features.

PMID- 15947087
TI  - KLF2 is essential for primitive erythropoiesis and regulates the human and murine
      embryonic beta-like globin genes in vivo.
AB  - The Kruppel-like factors (KLFs) are a family of C2/H2 zinc finger DNA-binding
      proteins that are important in controlling developmental programs. Erythroid
      Kruppel-like factor (EKLF or KLF1) positively regulates the beta-globin gene in
      definitive erythroid cells. KLF2 (LKLF) is closely related to EKLF and is
      expressed in erythroid cells. KLF2-/- mice die between embryonic day 12.5 (E12.5)
      and E14.5, because of severe intraembryonic hemorrhaging. They also display
      growth retardation and anemia. We investigated the expression of the beta-like
      globin genes in KLF2 knockout mice. Our results show that KLF2-/- mice have a
      significant reduction of murine embryonic Ey- and beta h1-globin but not zeta
      globin gene expression in the E10.5 yolk sac, compared with wild-type mice. The
      expression of the adult beta(maj)- and beta(min)-globin genes is unaffected in
      the fetal livers of E12.5 embryos. In mice carrying the entire human globin
      locus, KLF2 also regulates the expression of the human embryonic epsilon-globin
      gene but not the adult beta-globin gene, suggesting that this developmental-stage
      specific role is evolutionarily conserved. KLF2 also plays a role in the
      maturation and/or stability of erythroid cells in the yolk sac. KLF2-/- embryos
      have a significantly increased number of primitive erythroid cells undergoing
      apoptotic cell death.

PMID- 15947088
TI  - Functional abnormalities of heparan sulfate in mucopolysaccharidosis-I are
      associated with defective biologic activity of FGF-2 on human multipotent
      progenitor cells.
AB  - In mucopolysaccharidosis-I (MPS-I), alpha-L-iduronidase deficiency leads to
      progressive heparan sulfate (HS) and dermatan sulfate (DS) glycosaminoglycan
      (GAG) accumulation. The functional consequences of these accumulated molecules
      are unknown. HS critically influences tissue morphogenesis by binding to and
      modulating the activity of several cytokines (eg, fibroblast growth factors
      [FGFs]) involved in developmental patterning. We recently isolated a multipotent
      progenitor cell from postnatal human bone marrow, which differentiates into cells
      of all 3 embryonic lineages. The availability of multipotent progenitor cells
      from healthy volunteers and patients with MPS-I (Hurler syndrome) provides a
      unique opportunity to directly examine the functional effects of abnormal HS on
      cytokine-mediated stem-cell proliferation and survival. We demonstrate here that
      abnormally sulfated HS in Hurler multipotent progenitor cells perturb critical
      FGF-2-FGFR1-HS interactions, resulting in defective FGF-2-induced proliferation
      and survival of Hurler multipotent progenitor cells. Both the mitogenic and
      survival-promoting activities of FGF-2 were restored by substitution of Hurler HS
      by normal HS. This perturbation of critical HS-cytokine receptor interactions may
      represent a mechanism by which accumulated HS contributes to the developmental
      pathophysiology of Hurler syndrome. Similar mechanisms may operate in the
      pathogenesis of other diseases where structurally abnormal GAGs accumulate.

PMID- 15947089
TI  - Inhibition of mitochondrial respiration elevates oxygen concentration but leaves
      regulation of hypoxia-inducible factor (HIF) intact.
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) is critical for
      erythropoietin and other factors involved in the adaptation of the organism to
      hypoxic stress. Conflicting results have been published regarding the role of the
      mitochondrial electron transport chain (ETC) in the regulation of HIF-1alpha. We
      assessed cellular hypoxia by pimonidazole staining and blotting of the O2-labile
      HIF-1 alpha-subunit in human osteosarcoma cell cultures (U2OS and 143B). In
      conventional, gas-impermeable cell culture dishes, ETC inhibitors had no effect
      on pimonidazole staining or HIF-1alpha abundance in a 20% O2 atmosphere; both
      parameters were undetectable. Pimonidazole staining and HIF activity were
      substantial in 0.1% O2 irrespective of ETC inhibition. At an intermediate oxygen
      concentration (3% O2) pimonidazole staining and HIF-alpha expression were
      detectable but strongly reduced after ETC inhibition in conventional cell
      cultures. All effects of ETC inhibition on HIF-1alpha regulation were eliminated
      in gas-permeable dishes. As shown in a 143B subclone deficient in mitochondrial
      DNA (206rho0), genetic inactivation of the ETC led to similar responses with
      respect to HIF-1alpha regulation as ETC inhibitors. Our data demonstrate that
      reduction of oxygen consumption reduces the O2 gradient in conventional cell
      cultures, causing elevation of the cellular O2 concentration, which leads to
      degradation of HIF-alpha.

PMID- 15947090
TI  - The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics
      upon warfarin dose requirements: proposal for a new dosing regimen.
AB  - Current dosing algorithms do not account for genetic and environmental factors
      for warfarin dose determinations. This study investigated the contribution of
      age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements.
      Studied were 297 patients with stable anticoagulation with a target international
      normalized ratio (INR) of 2.0 to 3.0. Genetic analyses for CYP2C9 (*2 and *3
      alleles) and VKORC1 (-1639 polymorphism) were performed and venous INR and plasma
      R- and S-warfarin concentrations determined. The mean warfarin daily dose
      requirement was highest in CYP2C9 homozygous wild-type patients, compared with
      those with the variant *2 and *3 alleles (P < .001) and highest in patients with
      the VKORC1 (position -1639) GG genotype compared with those with the GA genotype
      and the AA genotype (P < .001). Mean warfarin daily dose requirements fell by 0.5
      to 0.7 mg per decade between the ages of 20 to 90 years. Age, height, and CYP2C9
      genotype significantly contributed to S-warfarin and total warfarin clearance,
      whereas only age and body size significantly contributed to R-warfarin clearance.
      The multivariate regression model including the variables of age, CYP2C9 and
      VKORC1 genotype, and height produced the best model for estimating warfarin dose
      (R2 = 55%). Based upon the data, a new warfarin dosing regimen has been
      developed. The validity of the dosing regimen was confirmed in a second cohort of
      patients on warfarin therapy.

PMID- 15947091
TI  - A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during
      dendritic-cell maturation.
AB  - Prostaglandins, a family of lipidic molecules released during inflammation,
      display immunomodulatory properties in several models. One use includes exposure
      of monocyte-derived dendritic cells (DCs) to a cocktail of cytokines that
      contains prostaglandin E2 (PGE2) for purposes of maturation; such cells are
      currently being used for cancer immunotherapy trials. Our analysis of the
      transcription profile of DCs matured in the presence of tumor necrosis factor
      alpha (TNFalpha) and PGE2 revealed a strong up-regulation of indoleamine 2-3
      dioxygenase (IDO), an enzyme involved in tryptophan catabolism and implicated in
      both maternal and T-cell tolerance. Using quantitative assays to monitor levels
      of IDO mRNA, protein expression, and enzyme activity, we report that PGE2 induces
      mRNA expression of IDO; however, a second signal through TNF receptor (TNF-R) or
      a Toll-like receptor (TLR) is necessary to activate the enzyme. Interestingly,
      use of TNFalpha, lipopolysaccharide, or Staphylococcus aureus Cowan I strain
      (SAC) alone does not induce IDO. The effect of PGE2 is mediated by activation of
      adenylate cyclase via the Gs-protein-coupled receptor E prostanoid-2 (EP2). A
      better understanding of these regulatory mechanisms and the crosstalk between TNF
      R/TLR and EP2 signaling pathways will provide insight into the regulation of T
      cell activation by DCs and may help to improve existing immunotherapy protocols.

PMID- 15947092
TI  - A novel molecular basis for beta thalassemia intermedia poses new questions about
      its pathophysiology.
AB  - During a study of the molecular basis for severe forms of beta thalassemia in Sri
      Lanka, 2 patients were found to be heterozygous for beta thalassemia mutations.
      Further analysis revealed that one of them has a previously unreported molecular
      basis for severe thalassemia intermedia, homozygosity for quadruplicated alpha
      globin genes in combination with heterozygous beta thalassemia. The other is
      homozygous for a triplicated alpha globin gene arrangement and heterozygous for
      beta thalassemia. Their differences in clinical phenotype are explainable by the
      interaction of other genetic factors and, in particular, their early management.
      The clinical course of the 2 propositi underlines the importance of full
      genotyping and a long period of observation before treatment is instituted,
      particularly in patients with beta thalassemia intermedia associated with
      extended alpha globin gene arrangements. The hemoglobin (Hb) F levels in these
      patients with severe beta thalassemia intermedia, compared with other forms of
      this condition in the Sri Lankan population and elsewhere, are unusually low, a
      consistent finding in extended alpha globin gene interactions and in dominant
      beta thalassemia, raising the possibility that increased levels of HbF production
      in beta thalassemia may require mutations at both beta globin gene loci.

PMID- 15947093
TI  - IL-7 receptor alpha chain expression distinguishes functional subsets of virus
      specific human CD8+ T cells.
AB  - Virus-specific CD8+ T cells emerge after infection with herpesviruses and
      maintain latency to these persistent pathogens. It has been demonstrated that
      murine memory CD8+ T-cell precursors specific for acute lymphocytic
      choriomeningitis virus express interleukin-7 receptor alpha (IL-7Ralpha), and IL
      7 is involved in maintaining memory populations after the clearance of antigen.
      To investigate whether human CD8+ T cells reactive toward persistent viruses are
      maintained similarly, we analyzed IL-7Ralpha expression and function on these
      virus-specific cells. During primary infection, all cytomegalovirus (CMV)
      specific CD8+ T cells and most Epstein-Barr virus (EBV)-specific CD8+ T cells
      lacked IL-7Ralpha expression. Only some virus-specific T cells expressed IL
      7Ralpha late after viral replication became undetectable. CD8+ T cells specific
      for cleared viruses, influenza (FLU), and respiratory syncytial virus (RSV) all
      expressed IL-7Ralpha. Remarkably, the percentage of IL-7Ralpha- CMV-specific T
      cells correlated with the height of viral replication in the acute phase. Virus
      specific IL-7Ralpha+ cells proliferated vigorously in response to IL-7, IL-15, or
      peptide, whereas IL-7Ralpha- cells required both peptide and helper-cell
      activation or IL-2 or IL-15 for optimal expansion. Our data suggest that although
      IL-7 is essential for the maintenance of memory cells in the absence of antigen,
      CD8+ T cells specific for latent viruses need T-cell receptor activation plus
      helper factors to persist.

PMID- 15947094
TI  - Identification of target genes and a unique cis element regulated by IRF-8 in
      developing macrophages.
AB  - Interferon regulatory factor-8 (IRF-8)/interferon consensus sequence-binding
      protein (ICSBP) is a transcription factor that controls myeloid-cell development.
      Microarray gene expression analysis of Irf-8-/- myeloid progenitor cells
      expressing an IRF-8/estrogen receptor chimera (which differentiate into
      macrophages after addition of estradiol) was used to identify 69 genes altered by
      IRF-8 during early differentiation (62 up-regulated and 7 down-regulated). Among
      them, 4 lysosomal/endosomal enzyme-related genes (cystatin C, cathepsin C,
      lysozyme, and prosaposin) did not require de novo protein synthesis for
      induction, suggesting that they were direct targets of IRF-8. We developed a
      reporter assay system employing a self-inactivating retrovirus and analyzed the
      cystatin C and cathepsin C promoters. We found that a unique cis element mediates
      IRF-8-induced activation of both promoters. Similar elements were also found in
      other IRF-8 target genes with a consensus sequence (GAAANN[N]GGAA) comprising a
      core IRF-binding motif and an Ets-binding motif; this sequence is similar but
      distinct from the previously reported Ets/IRF composite element. Chromatin
      immunoprecipitation assays demonstrated that IRF-8 and the PU.1 Ets transcription
      factor bind to this element in vivo. Collectively, these data indicate that IRF-8
      stimulates transcription of target genes through a novel cis element to specify
      macrophage differentiation.

PMID- 15947095
TI  - B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model,
      but does not adversely affect humoral responses in a respiratory syncytial virus
      (RSV) vaccination model.
AB  - We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22
      monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to
      characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine
      primary and secondary lymphoid tissues. The effect of B-cell depletion was
      further studied in a murine collagen-induced arthritis (CIA) model and a
      respiratory syncytial virus (RSV) vaccination model. Our results show that (1)
      the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B
      cell reconstitution starts in the bone marrow and spleen around day 30 after
      depletion and is completed in all tissues tested by day 50; (3) B-cell depletion
      inhibits the development of clinical and histologic arthritis in the CIA model;
      (4) depletion of type II collagen antibody levels is not necessary for clinical
      and histologic prevention of CIA; and (5) B-cell depletion does not adversely
      affect memory antibody responses after challenge nor clearance of infectious
      virus from lungs in the RSV vaccination model. These results demonstrate for the
      first time that only B-cell reduction but not type II collagen antibody levels
      correlate with the prevention of arthritis and represent key insights into the
      role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination
      models.

PMID- 15947096
TI  - Novel pathway for megakaryocyte production after in vivo conditional eradication
      of integrin alphaIIb-expressing cells.
AB  - Our knowledge of the molecular mechanisms that regulate hematopoiesis in
      physiologic and pathologic conditions is limited. Using a molecular approach
      based on cDNA microarrays, we demonstrated the emergence of an alternative
      pathway for mature bone marrow cell recovery after the programmed and reversible
      eradication of CD41+ cells in transgenic mice expressing a conditional toxigene
      targeted by the platelet alphaIIb promoter. The expression profile of the newly
      produced CD41+ cells showed high levels of transcripts encoding Ezh2, TdT, Rag2,
      and various immunoglobulin (Ig) heavy chains. In this context, we identified and
      characterized a novel population of Lin-Sca-1hi c-Kit- cells, with a lymphoid
      like expression pattern, potentially involved in the reconstitution process. Our
      study revealed novel transcriptional cross talk between myeloid and lymphoid
      lineages and identified gene expression modifications that occur in vivo under
      these particular stress conditions, opening important prospects for therapeutic
      applications.

PMID- 15947097
TI  - Breast-tissue sampling for risk assessment and prevention.
AB  - Breast tissue and duct fluid provide a rich source of biomarkers to both aid in
      the assessment of short-term risk of developing breast cancer and predict and
      assess responses to prevention interventions. There are three methods currently
      being utilized to sample breast tissue in asymptomatic women for risk assessment:
      nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA)
      and ductal lavage. Prospective single-institution trials have shown that the
      presence of atypical cells in NAF fluid or RPFNA specimens is associated with an
      increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been
      observed to further stratify risk based on the commonly used Gail risk-assessment
      model. A prospective trial evaluating risk prediction on the basis of atypical
      cells in ductal-lavage fluid is ongoing. The ability of other established non
      genetic biomarkers (mammographic breast density; serum levels of bioavailable
      estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth
      factor binding protein-3) to stratify risk based on the Gail model is as yet
      incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e.
      hyperplasia with or without atypia) with or without associated breast-tissue
      molecular markers, such as proliferation, is currently being used to evaluate
      response in Phase II chemoprevention trials. RPFNA has been the method most
      frequently used for Phase II studies of 6-12 months duration. However, ductal
      lavage, RPFNA and random and directed core needle biopsies are all being utilized
      in ongoing multi-institutional Phase II studies. The strengths and weaknesses of
      each method are reviewed.

PMID- 15947098
TI  - Tissue inhibitor of metalloproteinases-1 in breast cancer.
AB  - Whether patients diagnosed with primary breast cancer are offered adjuvant
      systemic therapy following surgical removal of the tumor is based on prognosis.
      Prognosis is estimated in every patient using established prognostic variables.
      Unfortunately, when using the currently available prognostic parameters a
      significant proportion of patients are over-treated. Thus, in order to improve
      stratification of breast cancer patients, additional prognostic factors need to
      be identified. Tissue inhibitor of metalloproteinases-1 (TIMP-1) is one of the
      promising candidates for new prognostic markers in breast cancer, as a number of
      studies have demonstrated an association between high tumor-tissue levels of TIMP
      1 mRNA as well as TIMP-1 protein and a poor prognosis of breast cancer patients.
      TIMP-1 is a member of the TIMP family, currently comprising four members (TIMP-1
      4), and its main function is inhibition of the activity of various matrix
      metalloproteinases (MMPs). The association between high levels of protease
      inhibitor and poor prognosis may be somewhat surprising, as proteolytic activity
      plays a pivotal role in cancer cell invasion and metastasis. However, the recent
      discovery of other biological functions of TIMP-1 such as growth-stimulating
      functions, as well as anti-apoptotic and pro-angiogenetic effects, may in part
      explain this paradox. The purpose of this review is to give an update on the
      current status of TIMP-1 in breast cancer, emphasizing the prognostic utility of
      the inhibitor. In addition, the suggested tumor-stimulatory roles of TIMP-1 will
      be outlined.

PMID- 15947099
TI  - Mechanisms of endocrine therapy-responsive and -unresponsive prostate tumours.
AB  - Several options for the endocrine treatment of non-organ-confined prostate cancer
      are available. They include surgical or medical removal of androgenic hormones or
      administration of non-steroidal anti-androgens. However, tumour progression after
      a period of remission of the disease inevitably occurs in virtually all patients.
      The androgen receptor (AR) is, in various tumour models, implicated in the
      development of therapy resistance but molecular mechanisms that by-pass the
      receptor have also been described. Adaptation mechanisms relevant to tumour
      recurrence include up-regulation of AR mRNA and protein, overexpression of AR
      coactivators, increased activation of mutated receptors by steroids and anti
      androgens, and ligand-independent activation. For research studies, sublines that
      respond to but do not depend on androgen for their proliferation were generated.
      Coactivators SRC-1, TIF-2, RAC3, p300, CBP, Tip60, and gelsolin are highly
      expressed in endocrine therapy-resistant prostate cancer. AR point mutations are
      increasingly detected in relapsed cancers and contribute to the failure of
      endocrine therapy in a subgroup of patients. Ligand-independent activation of the
      AR by HER-2/neu and interleukin-6 is associated with activation of the signalling
      pathway of mitogen-activated protein kinase. Increased activity of intracellular
      kinases may affect cellular events in both an AR-dependent and -independent
      manner. Mitogen-activated protein kinases are strongly phosphorylated in
      endocrine therapy-resistant prostate tumours. Similarly, activation of the AR by
      phosphorylated protein kinase B, Akt, has also been reported in prostate cancer.
      Activation of the Akt pathway contributes to increased survival of prostate
      tumour cells.

PMID- 15947100
TI  - BRAF mutation in thyroid cancer.
AB  - Genetic alteration is the driving force for thyroid tumorigenesis and
      progression, based upon which novel approaches to the management of thyroid
      cancer can be developed. A recent important genetic finding in thyroid cancer is
      the oncogenic T1799A transversion mutation of BRAF (the gene for the B-type Raf
      kinase, BRAF). Since the initial report of this mutation in thyroid cancer 2
      years ago, rapid advancements have been made. BRAF mutation is the most common
      genetic alteration in thyroid cancer, occurring in about 45% of sporadic
      papillary thyroid cancers (PTCs), particularly in the relatively aggressive
      subtypes, such as the tall-cell PTC. This mutation is mutually exclusive with
      other common genetic alterations, supporting its independent oncogenic role, as
      demonstrated by transgenic mouse studies that showed BRAF mutation-initiated
      development of PTC and its transition to anaplastic thyroid cancer. BRAF mutation
      is mutually exclusive with RET/PTC rearrangement, and also displays a reciprocal
      age association with this common genetic alteration in thyroid cancer. The T1799A
      BRAF mutation occurs exclusively in PTC and PTC-derived anaplastic thyroid cancer
      and is a specific diagnostic marker for this cancer when identified in
      cytological and histological specimens. This mutation is associated with a poorer
      clinicopathological outcome and is a novel independent molecular prognostic
      marker in the risk evaluation of thyroid cancer. Moreover, preclinical and
      clinical evaluations of the therapeutic value of novel specific mitogen-activated
      protein kinase pathway inhibitors in thyroid cancer are anticipated. This newly
      discovered BRAF mutation may prove to have an important impact on thyroid cancer
      in the clinic.

PMID- 15947101
TI  - Low molecular weight proteomic information distinguishes metastatic from benign
      pheochromocytoma.
AB  - Metastatic lesions occur in up to 36% of patients with pheochromocytoma.
      Currently there is no way to reliably detect or predict which patients are at
      risk for metastatic pheochromocytoma. Thus, the discovery of biomarkers that
      could distinguish patients with benign disease from those with metastatic disease
      would be of great clinical value. Using surface-enhanced laser desorption
      ionization protein chips combined with high-resolution mass spectrometry, we
      tested the hypothesis that pheochromocytoma pathologic states can be reflected as
      biomarker information within the low molecular weight (LMW) region of the serum
      proteome. LMW protein profiles were generated from the serum of 67
      pheochromocytoma patients from four institutions and analyzed by two different
      bioinformatics approaches employing pattern recognition algorithms to determine
      if the LMW component of the circulatory proteome contains potentially useful
      discriminatory information. Both approaches were able to identify combinations of
      LMW molecules which could distinguish all metastatic from all benign
      pheochromocytomas in a separate blinded validation set. In conclusion, for this
      study set low molecular mass biomarker information correlated with
      pheochromocytoma pathologic state using blinded validation. If confirmed in
      larger validation studies, efforts to identify the underlying diagnostic
      molecules by sequencing would be warranted. In the future, measurement of these
      biomarkers could be potentially used to improve the ability to identify patients
      with metastatic disease.

PMID- 15947102
TI  - Life expectancy in differentiated thyroid cancer: a novel approach to survival
      analysis.
AB  - In differentiated thyroid carcinoma 10-year survival rates amount to 80-95%.
      Because age at diagnosis varies widely, these survival rates strongly depend on
      age at presentation. The aim of the present study was to analyse the attributable
      risk factors, including therapy per se, on survival in thyroid cancer after
      proper adjustment for the baseline mortality rate in the general population and
      to elucidate the adverse treatment effects on survival. Initial treatment in 504
      patients consisted of thyroidectomy and 131I ablation. High-dose 131I was
      administered for residual disease. Patients in complete remission underwent an
      annual physical examination and thyroglobulin measurements during TSH
      suppression. Survival time was studied after transformation to standardised
      survival time to adjust for the baseline mortality rate in the general
      population. Median follow-up since diagnosis was 9 years. The 10-year overall
      survival was 83% and disease-specific survival 91%. After initial treatment,
      persistent disease occurred in 75 patients (15%). In univariate analysis, T4, N1,
      M1 status and Hurthle cell type were prognostic for persistent and recurrent
      disease. Age was not prognostic for recurrent disease in multivariate analysis.
      The standardised survival time was not altered in disease-free patients. However,
      patients with persistent disease had a median standardised survival time of only
      0.60 (95% confidence interval 0.47;0.72), ranging from 0 to above 1, independent
      of initial tumour status or age. The cumulative proportion of persistent disease
      was at least 20% of the whole group. Disease-free patients after thyroid
      carcinoma have a normal residual life span. In contrast, in cases of persistent
      disease the life expectancy ranges widely with its median being reduced to 60%.
      Overall, treatment including radioiodine is safe but unsuccessful in 20% of the
      patients. Age is not a disease-specific risk factor and should not be used as an
      independent factor in treatment algorithms.

PMID- 15947103
TI  - Medullary and papillary carcinoma of the thyroid gland occurring as a collision
      tumour: report of three cases with molecular analysis and review of the
      literature.
AB  - We report the simultaneous occurrence of medullary thyroid carcinoma (MTC) and
      papillary thyroid carcinoma (PTC), presenting as spatially distinct and well
      defined tumour components, in three cases. In the first patient, histology,
      immunohistochemistry and electron microscopy demonstrated an MTC in the one
      nodule and PTC in two additional lesions. Non-neoplastic thyroid parenchyma
      separated the three nodules. Metastasis from PTC was diagnosed in a regional
      lymph node. Genetic analysis of both tumour components showed a distinctive
      mutational pattern: in the MTC a Cys634Arg substitution in exon 11 of the RET
      gene and in the two PTC foci a Val600Glu substitution in exon 15 of the BRAF
      gene. The other two patients are members of a large multigenerational family
      affected with familial MTC due to a germline mutation of the RET gene
      (Ala891Ser). Both patients harboured, besides medullary cancer and C-cell
      hyperplasia, distinct foci of papillary thyroid cancer, which was positive for
      Val600Glu BRAF mutation. Review of the literature disclosed 18 similar lesions
      reported and allowed the identification of different patterns of clinical
      presentation and biological behaviour. So far, the pathogenesis of these peculiar
      cases of thyroid malignancy has been completely unknown, but an underlying common
      genetic drive has been hypothesised. This is the first report in which two
      mutations, in the RET and BRAF genes, have been identified in three cases of
      MTC/PTC collision tumour, thus documenting the different genetic origin of these
      two coexisting carcinomas.

PMID- 15947104
TI  - Action of thiazolidinediones on differentiation, proliferation and apoptosis of
      normal and transformed thyrocytes in culture.
AB  - Differentiating drugs may be able to re-sensitize thyroid carcinomas to
      radioiodine therapy. Substituted thiazolidinediones (TZDs) belong to the group of
      oral anti-diabetic drugs that also possess anti-proliferative and pro-apoptotic
      effects and, potentially, differentiating effects on several cancer cell lines.
      Some of the effects are mediated via the peroxisome proliferator-activated
      receptor gamma (PPAR-gamma). We investigated the effect of troglitazone,
      rosiglitazone and pioglitazone on differentiation in normal porcine thyrocytes
      and in the follicular carcinoma cell lines FTC 133 and FTC 238. Differentiation
      was investigated by measuring 125I uptake and the expression of sodium-iodide
      symporter and thyroglobulin proteins. The TZDs were tested in the presence of
      retinol and retinoic acid. Additionally, proliferation was evaluated by
      [3H]thymidine uptake and cell number and apoptosis by annexin V-labeling.
      Controls included tocopherol and unsubstituted thiazolidinedione and co
      incubation of the TZDs with the PPAR-gamma antagonist GW9662. PPAR-gamma and
      retinol X receptor (RXR)-alpha were investigated by immunocytochemistry, Western
      blot and RT-PCR. Cells derived from the metastasis showed greater responses than
      cells derived from the primary tumor. Troglitazone showed greater effects than
      the other TZDs. Troglitazone significantly increased 125I uptake and apoptosis
      and decreased [3H]thymidine uptake and cell number. The amount of the sodium
      iodide-symporter in the membrane fraction was significantly increased, while that
      of thyroglobulin was not influenced by the treatment. Inclusion of antagonist did
      not abolish these effects. No synergistic effect with any retinoid was detected.
      All transformed cells expressed PPAR-gamma and RXR-alpha but TZDs did not change
      their expression. Troglitazone appears to be suited for the re-differentiation
      treatment of dedifferentiated thyroid carcinoma because its action is twofold. On
      the one hand it increases differentiation and on the other hand it inhibits
      proliferation.

PMID- 15947105
TI  - Characterization of thyroid 'follicular neoplasms' in fine-needle aspiration
      cytological specimens using a panel of immunohistochemical markers: a proposal
      for clinical application.
AB  - The distinction of benign from malignant follicular thyroid neoplasms remains a
      difficult task in diagnostic fine-needle aspiration cytology, and some discrepant
      results have been reported for the individual immunocytochemical markers of
      malignancy proposed so far. The aim of this study was to test if the combined use
      of a panel of markers could improve the diagnostic accuracy in the preoperative
      cytological evaluation of 'follicular neoplasms' in an attempt to reduce the
      number of thyroidectomies performed for benign lesions. The immunocytochemical
      expression of galectin-3, HBME-1, thyroperoxidase, cytokeratin-19 and keratan
      sulfate was retrospectively analyzed in 125 consecutive fine-needle aspiration
      samples (cell blocks) of indeterminate diagnoses of 'follicular thyroid
      neoplasm', and compared with their corresponding surgical specimens, including 33
      follicular carcinomas, 42 papillary carcinomas and 50 follicular adenomas.
      Statistical analysis on each marker confirmed that galectin-3 and HBME-1 were the
      most sensitive (92% and 80% respectively) and specific (94% and 96% respectively)
      molecules. The use of these two markers sequentially in non-oncocytic lesions
      (testing HBME-1 as a second marker whenever galectin-3 proved negative) increased
      the sensitivity and specificity up to 97% and 95% respectively. In oncocytic
      lesions, HBME-1 proved to be less sensitive, and the sequential combination of
      galectin-3 and cytokeratin-19 reached 100% of both specificity and sensitivity.
      Our data showed that, as compared with the use of single markers, the sequential
      combination of two markers represents the most accurate immunohistochemical panel
      in managing patients with a fine-needle aspiration biopsy diagnosis of
      'follicular neoplasms', especially in otherwise controversial categories such as
      oncocytic tumours. The combination of three or more markers did not substantially
      improve the diagnostic accuracy of the test.

PMID- 15947106
TI  - RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation
      of genes involved in regulation of the immune response.
AB  - RET/PTC rearrangements represent key genetic events involved in papillary thyroid
      carcinoma (PTC) initiation. The aim of the present study was to identify the
      early changes in gene expression induced by RET/PTC in thyroid cells. For this
      purpose, microarray analysis was conducted on PCCL3 cells conditionally
      expressing the RET/PTC3 oncogene. Gene expression profiling 48 h after activation
      of RET/PTC3 identified a statistically significant modification of expression of
      270 genes. Quantitative PCR confirmation of 20 of these demonstrated 90% accuracy
      of the microarray. Functional clustering of genes with greater than or less than
      1.75-fold expression change (86 genes) revealed RET/PTC3-induced regulation of
      genes with key functions in apoptosis (Ripk3, Tdga), cell-cell signaling (Cdh6,
      Fn1), cell cycle (Il24), immune and inflammation response (Cxcl10, Scya2, Il6,
      Gbp2, Oas1, Tap1, RT1Aw2, C2ta, Irf1, Lmp2, Psme2, Prkr), metabolism (Aldob,
      Ptges, Nd2, Gss, Gstt1), signal transduction (Socs3, Nf1, Jak2, Cpg21, Dusp6,
      Socs1, Stat1, Stat3, Cish) and transcription (Nr4a1, Junb, Hfh1, Runx1, Foxe1).
      Genes coding for proteins involved in the immune response and in intracellular
      signal transduction pathways activated by cytokines and chemokines were strongly
      represented, indicating a critical role of RET/PTC3 in the early modulation of
      the immune response.

PMID- 15947107
TI  - Alterations in the regulatory volume decrease (RVD) and swelling-activated Cl-
      current associated with neuroendocrine differentiation of prostate cancer
      epithelial cells.
AB  - Neuroendocrine (NE) differentiation of prostate epithelial/basal cells is a
      hallmark of advanced, androgen-independent prostate cancer, for which there is no
      successful therapy. Here we report for the first time on alterations in
      regulatory volume decrease (RVD) and its key determinant, swelling-activated Cl-
      current (I(Cl,swell)), associated with NE differentiation of androgen-dependent
      LNCaP prostate cancer epithelial cells. NE-differentiating regimens, namely,
      chronic cAMP elevation or androgen deprivation, resulted in generally augmented
      I(Cl,swell) and enhanced RVD. This occurred as a result of both the increased
      endogenous expression of ClC-3, which is a volume-sensitive Cl- channel involved,
      as we show, in I(Cl,swell) in LNCaP (lymph-node carcinoma of the prostate) cells
      and the weaker negative I(Cl,swell) control from Ca2+ entering via store
      dependent pathways. The changes in the RVD of NE-differentiated cells generally
      mimicked those reported for Bcl-2-conferred apoptotic resistance. Our results
      suggest that strengthening the mechanism that helps to maintain volume constancy
      may contribute to better survival rates of apoptosis-resistant NE cells.

PMID- 15947108
TI  - Identification of growth factor independent-1 (GFI1) as a repressor of 25
      hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate
      cancer cells.
AB  - The hormone 1,25-dihydroxyvitamin D (1,25D) may play a protective role in
      prostate cancer. 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) is the enzyme
      responsible for the regulation of cellular 1,25D levels. CYP27B1 is substantially
      repressed in prostate cancer cells. We have investigated the molecular basis for
      this inhibition. First, we identify a repressive region between -997 and -1200 in
      the human CYP27B1 promoter following transient transfection analysis in the
      prostate cancer cell lines DU145, PC3 and LNCaP. Next, we demonstrate a role for
      the transcription factor growth factor independent-1 (GFI1) in the repression of
      CYP27B1. Electrophoretic mobility assays with nuclear extracts from prostate
      cancer cell lines established binding of GFI1 to the sequence 5'
      TGGTACAATCATAACTCACTGCAG-3' present at -997 to -1200 in the repressive region.
      Site directed mutagenesis of the core GFI1 binding sequence (5'-AATC-3')
      substantially increased while forced expression of GFI1 decreased the expression
      of the CYP27B1 reporter construct. Importantly, GFI1 repression is dependent on
      an intact GFI1 binding site in the -997 to -1200 region. GFI1 is an oncoprotein
      known to form a large protein complex with co-repressors that recruit histone
      deacetylases. We propose that the formation of such a repressive complex on the
      inhibitory domain of the CYP27B1 gene in prostate cancer cells could lead to
      silencing of either the nearby enhancer or proximal promoter domains and lead to
      cancer progression by reducing local production of 1,25D. These studies provide
      the basis for a more detailed understanding of CYP27B1 repression in prostate
      cancer cells and could provide a novel insight in future diagnosis and treatment.

PMID- 15947109
TI  - Evidence for specific TRPM8 expression in human prostate secretory epithelial
      cells: functional androgen receptor requirement.
AB  - TRPM8 (melastatine-related transient receptor potential member 8), a member of
      the transient receptor potential (TRP) superfamily of cation channels, has been
      shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be
      overexpressed in prostate cancer and is considered to play an important role in
      prostate physiology. This study was designed to determine the androgen-regulation
      mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8
      expressing cells in the human prostate. Our findings show that trpm8 gene
      expression requires a functional androgen receptor. Furthermore, this article
      argues strongly in favour of the fact that the trpm8 gene is a primary androgen
      responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical
      experiments also showed that the trpm8 gene was mainly expressed in the apical
      secretory epithelial cells of the human prostate and trpm8 down-regulation
      occurred during the loss of the apical differentiated phenotype of the primary
      cultured human prostate epithelial cells. The androgen-regulated trpm8 expression
      mechanisms are important in understanding the progression of prostate cancer to
      androgen-independence. These findings may contribute to design a strategy to
      predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the
      TRPM8 channel is localized in human prostate cells, it will be interesting to
      understand its physiological function in the normal prostate and its potential
      role in prostate cancer development.

PMID- 15947110
TI  - Cytotoxic and antiproliferative activity of the single agent epirubicin versus
      epirubicin plus tamoxifen as primary chemotherapy in human breast cancer: a
      single-institution phase III trial.
AB  - This study was designed to address whether simultaneous primary chemo-hormonal
      therapy provides additional activity compared with chemotherapy alone in breast
      cancer patients with operable or locally advanced disease. Between January 1997
      and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were
      randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen
      (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens
      obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor
      shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and
      81.9% of patients randomized in the EPI-TAM arm (not significant). The
      corresponding rates of clinical and pathological complete response were 20.2 and
      21.9% (not significant), and 4.8 and 6.7% (not significant), respectively.
      Pathologically complete response was more frequently observed in estrogen
      receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated
      baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a
      significant reduction in Ki67 expression, either in overall patients (P=0.000) or
      in patients with ER+ breast cancer (P=0.000). The reduction in Ki67
      immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a
      lower Ki67 expression at post-operative residual histology (P=0.0041). The
      addition of tamoxifen to epirubicin chemotherapy did not improve the response
      rate but led to a significantly higher reduction in the Ki67 expression. Baseline
      elevated Ki67 expression and the ER- status were both associated with a greater
      chance of obtaining a pathological complete response at residual histology.

PMID- 15947111
TI  - The 67 kDa laminin receptor increases tumor aggressiveness by remodeling laminin
      1.
AB  - The association between expression of the 67 kDa laminin receptor (67LR) and
      tumor aggressiveness has been convincingly demonstrated although the exact
      function of this molecule in the metastatic process has remained unclear. In this
      study, we tested whether the laminin-1, upon interaction with 67LR, promotes
      tumor cell aggressiveness; the investigation was based on: (i) the previous
      demonstration that soluble 67LR, as well as a 20-amino-acid peptide corresponding
      to the 67LR laminin binding site, changes the conformation of laminin upon
      interaction with this adhesion molecule and (ii) the known relevance of
      microenvironment remodeling by the tumor, leading to structural modification of
      extracellular matrix components in tumor progression. MDAMB231 breast carcinoma
      cells plated on peptide G-treated laminin-1 exhibited a polygonal array of actin
      filament bundles compared with cells seeded on native laminin-1 which presented
      the actin bundles organized as multiple cables parallel to margins. Furthermore,
      in cells seeded on peptide G-treated laminin-1, 67LR was distinct from the alpha6
      integrin subunit in filopodia protrusions in addition to colocalizing with this
      integrin in focal adhesion plaques as it occurs when cells are plated on native
      laminin-1. In addition to differences in tumor cell adhesion and migration found
      in cells exposed to peptide G-treated vs native laminin-1, breast carcinoma cells
      seeded on modified laminin-1 showed a 6-fold increase in invasion capability
      compared with cells seeded on unmodified laminin-1. Alterations in actin
      organization as well as adhesion, migration and especially invasion observed in
      MDAMB231 cells in the presence of peptide G-treated laminin-1 were even found in
      MDAMB231 cells that, after selection for 67LR high expression, were seeded on
      native laminin-1. As the 67LR shedding is proportional to its expression level,
      these findings indicate a role for 67LR in changing laminin structure. Expression
      analysis of 97 genes encoding proteins that mediate cell matrix interactions,
      revealed significant differences between cells exposed to modified vs unmodified
      laminin-1 in 19 genes, 17 of which--including those encoding alpha3 integrin,
      extracellular matrix protein 1, proteolytic enzymes (such as MT1-MMP, stromelysin
      3 and cathepsin L) and their inhibitors--were up-modulated in cells treated with
      modified laminin-1. Zymogram analysis clearly indicated a significant increase in
      the activity of the gelatinolytic enzyme MMP-2 in the culture supernatant from
      cells exposed to modified laminin-1, without an increase in mRNA abundance as
      observed in microarray analysis. Invasiveness of tumor cells conditioned by
      modified laminin-1, evaluated as the capability to cross Matrigel basement, was
      significantly more inhibited by MMPinhibitor TIMP-2 than invasiveness induced by
      native laminin-1. Taken together, our findings indicate that the role of 67LR in
      tumor aggressiveness rests in its ability to modify laminin-1 thereby activating
      proteolytic enzymes that promote tumor cell invasion through extracellular matrix
      degradation.

PMID- 15947112
TI  - Gonadotropins upregulate the epidermal growth factor receptor through activation
      of mitogen-activated protein kinases and phosphatidyl-inositol-3-kinase in human
      ovarian surface epithelial cells.
AB  - Gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      have been implicated as probable risk factors in epithelial ovarian carcinomas,
      most of which are derived from ovarian surface epithelium (OSE). Since epidermal
      growth factor (EGF) increases the growth of ovarian surface epithelial cells, we
      determined the effect of gonadotropins on the expression of epidermal growth
      factor receptor (EGFR). We investigated the basal levels of EGFR mRNA and
      protein, and the mechanisms involved in the regulation of EGFR at the
      transcriptional and translational levels by FSH and LH. The immortalized OSE cell
      lines (IOSE) derived from normal OSE cells by transfecting SV40 T-antigen (IOSE
      80 and IOSE-80PC, a post-crisis line) and ovarian cancer cell lines were
      employed. A significantly lower level of EGFR was observed in both IOSE-80 and
      IOSE-80PC cells when compared with the ovarian cancer cell lines, OVCAR-3 and
      SKOV-3. Treatment of IOSE-80PC cells with FSH and LH (10(-7) and 10(-6) g/ml)
      resulted in a significant increase in EGFR mRNA at 24 h and EGFR protein at 48 h,
      whereas the treatment with gonadotropins for 24-48 h induced a mild increase in
      EGFR in OVCAR-3, but not in SKOV-3 cells. In addition, IOSE-80PC cells treated
      with gonadotropins and EGF (10 nM) exhibited an additive stimulation of
      mitogenesis. Further, FSH and LH significantly increased activities of various
      kinases at 5-10 min, and pre-treatments with LY294002 (an inhibitor of PI3K) or
      PD98059 (an inhibitor of ERK1/2) partially blocked the gonadotropin-induced up
      regulation of EGFR in IOSE-80PC cells. We investigated whether the effect of
      gonadotropins on EGFR mRNA levels is induced by increased transcription and/or by
      altered mRNA stability. Treatment of IOSE-80PC cells with FSH (10(-7) and 10(-6)
      g/ml) significantly enhanced the activity of the EGFR promoter (120 and 140%
      increase, respectively) at 24 h, and treatment with LH (10(-7) g/ml) for 24 h
      induced an increase in the activity of EGFR promoter (30%) in these cells. On the
      other hand, LH resulted in a significant increase in EGFR mRNA stability in the
      decay curves. Taken together, these results suggest that the effect of
      gonadotropins on the expression of EGFR may affect cell growth via ERK-1/-2 and
      PI3K pathways in pre-neoplastic ovarian surface epithelial cells, and that FSH
      and LH increase EGFR mRNA by different mechanisms. The former increased EGFR gene
      transcription essentially, whereas the latter mainly enhanced EGFR mRNA
      stability.

PMID- 15947113
TI  - Enhanced protein kinase B/Akt signalling in pituitary tumours.
AB  - Pituitary tumours have previously been shown to harbour several abnormalities
      that cause deregulation of the cell cycle, particularly down-regulation of
      expression of the cyclin-dependent kinase inhibitor p27. However, it has been
      unclear whether these are the primary initiating events, or are secondary to
      other more proximate alterations in signalling pathways. In other cellular
      systems the Akt signalling pathway has been associated with downstream modulation
      of cell-cycle control. The aim of the present study was to test the hypothesis
      that Akt signalling is enhanced in pituitary tumours, and to see if changes in
      Akt expression are related to previous findings on low expression levels of the
      nuclear cell-cycle inhibitor p27 in pituitary tumours. We examined normal and
      adenomatous human pituitary tissue for mRNA and protein expression of Akt1, Akt2
      and p27, and the activation of Akt, as well the phosphatase involved in the
      inactivation of Akt, phosphatase and tensin homologue deleted on chromosome 10
      (PTEN). In pituitary adenomas Akt1 and Akt2 mRNA were found to be over-expressed
      compared with normal pituitary, while PTEN transcripts showed similar levels
      between the two tissue types. Immunohistochemical expression of phospho-Akt was
      found to be higher in the tumours than normal pituitaries, while the protein
      expression of nuclear p27 and PTEN was lower in the adenomas. However, the
      expression of p27 and Akt were not directly correlated. PTEN sequencing revealed
      no mutation in the coding region of the gene in pituitary adenomas, and thus we
      did not locate a cause for the increased phosphorylation of Akt. In summary, we
      have shown over-expression and activation of the Akt pathway in pituitary
      tumours, and we speculate that cell-cycle changes observed in such tumours are
      secondary to these more proximate alterations. Since Akt is a major downstream
      signalling molecule of growth factor-liganded tyrosine kinase receptors, our data
      are most compatible with an abnormality at this level as the primary driver of
      pituitary tumorigenesis.

PMID- 15947114
TI  - Chromosomal instability predicts metastatic disease in patients with insulinomas.
AB  - Endocrine pancreatic tumors (EPTs) comprise a highly heterogeneous group of
      tumors with different clinical behavior and genetic makeup. Insulinomas represent
      the predominant syndromic subtype of EPTs. The metastatic potential of
      insulinomas can frequently not be predicted using histopathological criteria, and
      also molecular markers indicating malignant progression are unreliable because of
      the small number of cases per subtype studied so far. For the identification of
      reliable indicators of metastatic disease, we investigated 62 sporadic
      insulinomas (44 benign and 18 tumors with metastases) by means of comparative
      genomic hybridization (CGH). In addition, the role of MEN1 (multiple endocrine
      neoplasia type 1) gene mutations was determined to assess specific chromosomal
      alterations associated with dysfunction of this endocrine tumor-related tumor
      suppressor gene. Only one case with a somatic MEN1 mutation was identified
      (1527del7bp), indicating that the MEN1 gene plays a minor pathogenic role in
      sporadic insulinomas. CGH analysis revealed that the total number of aberrations
      per tumor differs strongly between the benign and the malignant group (4.2 vs
      14.1; P<0.0001). Furthermore, chromosome 9q gain was found to be the most
      frequent aberration in both benign and malignant insulinomas, whereas chromosome
      6q losses and 12q, 14q and 17pq gains are strongly associated with metastatic
      disease. Our study shows that chromosomal instability, as defined by > or =5
      gains together with > or =5 losses, or total number of gains and losses > or =8,
      rather than parameters such as tumor size and proliferation index, is the most
      powerful indicator for the development of metastatic disease in patients with
      sporadic insulinoma.

PMID- 15947115
TI  - Malign cystic glucagonoma presented with diabetic ketoacidosis: case report with
      an update.
AB  - A 44-year-old woman was diagnosed with type II diabetes in 1998 and 1 year later
      she developed necrolytic migratory erythema, which is a specific skin lesion of
      glucagonoma. During the clinical investigation, a nodular 6 cm mass in the distal
      pancreatic region and multiple cystic liver metastases were found. She was
      operated on, and glucagonoma was detected and the long-acting, repeatable,
      octreotide treatment was started. 3 years after resection of a pancreatic
      glucagonoma she presented to a hospital emergency department with diabetic
      ketoacidosis. Hepatic multiple cystic metastases were visualized by computed
      tomography. During hospitalization she developed severe pulmonary embolism and
      deep-venous thrombosis of the lower extremities. Indium-labeled octeotide
      scintigraphy showed multiple cystic lesions in the liver with additional lesions
      in the iliocecal region, which had not been visualized by computed tomography.
      Despite somatostatin therapy the tumor had expanded in the liver. Arterial
      chemoembolization was performed but 6 months later she died.

PMID- 15947116
TI  - ERbeta is a potent inhibitor of cell proliferation in the HCT8 human colon cancer
      cell line through regulation of cell cycle components.
AB  - Several strands of evidence indicate that oestrogens exert a protective role
      against the development of colon cancer through indirect and direct effects on
      colonic epithelium. Oestrogen receptor beta (ERbeta), the predominant ER subtype
      in human colon, is significantly decreased in colonic tumours compared with
      normal mucosa suggesting a potential role in the regulation of colon tumour
      growth. To investigate this hypothesis we engineered human colon cancer ERalpha
      negative HCT8 cells in order to obtain ERbeta protein over-expression. Stably
      transfected cells were cloned and ERbeta expression and functionality were
      monitored by RT-PCR, Western blotting and transactivation in an assay using
      oestrogen-responsive reporter constructs. Over-expression of ERbeta inhibited
      cell proliferation and increased cell adhesion in a ligand-independent manner.
      Its constitutive activation is possibly due to cross-talk with intracellular
      signalling pathways, as epidermal growth factor and IGF-I were able to induce
      ERbeta transactivation. A possible mechanism by which ERbeta over-expression
      inhibits proliferation in HCT8 cells is by modulation of some key regulators of
      the cell cycle; there is a decrease in cyclin E and an increase in the cdk
      inhibitor p21CIP1. In fact, flow cytometry analysis provided evidence for
      blocking of the G1-S phase progression induced by ERbeta over-expression. The
      magnitude of this effect was affected by the level of ERbeta expression. These
      results provide the first direct evidence that ERbeta plays an important role in
      colon cancer as a regulator of cell proliferation through the control of key cell
      cycle modulators and arrest in G1-S phase transition. These findings are
      compatible with the hypothesis that the loss of ERbeta expression could be one of
      the events involved in the development or progression of colon cancer.

PMID- 15947117
TI  - Gefitinib inhibits the ability of human bone marrow stromal cells to induce
      osteoclast differentiation: implications for the pathogenesis and treatment of
      bone metastasis.
AB  - Significant relief of bone pain in patients with bone metastases was observed in
      a clinical trial of the epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitor gefitinib in breast cancer. Osteoclast activation and differentiation
      are regulated by bone marrow stromal cells (BMSC), a heterogeneous cell
      compartment that comprehends undifferentiated mesenchymal stem cells (MSC) and
      their specialized progeny. In this regard, we found that human primary BMSCs
      express immunoreactive EGFR. Expression of EGFR mRNA and protein was also
      demonstrated in two human, continuous MSC-like cell lines, HDS-1 and HDS-2 cells.
      Treatment of HDS cells with EGF produced a significant increase in the levels of
      activated EGFR which was not observed in the presence of gefitinib. A significant
      reduction in the basal levels of activation of the EGFR and of Akt was observed
      in HDS cells following treatment with gefitinib. Treatment of HDS cells with
      gefitinib produced a significant reduction in the levels of secreted macrophage
      colony-stimulating factor (M-CSF) and cell-associated receptor activator of NF
      kappaB ligand (RANKL) in both cell lines, as assessed by using specific ELISA and
      Western blotting techniques. Finally, the ability to sustain the differentiation
      of pre-osteoclasts of conditioned medium from gefitinib-treated HDS cells was
      reduced by approximately 45% as compared with untreated HDS cells. These data
      have demonstrated for the first time that the EGFR regulates the ability of BMSCs
      to induce osteoclast differentiation and strongly support clinical trials of
      gefitinib in breast cancer patients with bone disease.

PMID- 15947118
TI  - High-mobility group box 1 protein is an inflammatory mediator in necrotizing
      enterocolitis: protective effect of the macrophage deactivator semapimod.
AB  - High-mobility group box 1 (HMGB1) is a late mediator of endotoxemia known to
      stimulate the production of proinflammatory cytokines that are putative mediators
      of intestinal inflammation associated with necrotizing enterocolitis (NEC). We
      hypothesized that HMGB1 is also involved in the pathogenesis of NEC. We examined
      the expression of HMGB1 and the effect of the novel drug semapimod on intestinal
      inflammation in an experimental model of NEC in neonatal rats. Newborn rats were
      subjected to hypoxia and fed a conventional formula by gavage (FFH) or were
      breast fed (BF). Rats were killed on day 4, and the distal ileum was harvested
      for morphological studies and Western blot analysis. FFH newborn rats but not BF
      controls developed intestinal inflammation similar to the histological changes
      observed in human NEC. We found that the expression of HMGB1 and its receptor for
      advanced glycation end products (RAGE) as well as that of other
      apoptosis/inflammation-related proteins (Bad, Bax, inducible nitric oxide
      synthase, and cyclooxygenase 2) was upregulated in the ileal mucosa of FFH
      newborn rats compared with BF animals. Administration of the drug semapimod
      inhibited the upregulation of those proteins and partially protected the animals
      against the FFH-induced intestinal injury. Elevated levels of HMGB1 were also
      found in ileal samples from infants undergoing intestinal resection for acute
      NEC. Our results implicate HMGB1 and RAGE as important mediators of enterocyte
      cell death and hypoxia-induced injury in NEC and support the hypothesis that
      inhibitors such as semapimod might play a therapeutic role in chronic intestinal
      inflammation characterized by this animal model.

PMID- 15947119
TI  - Current measures of PTSD for children and adolescents.
AB  - OBJECTIVE: To review measures of posttraumatic stress disorder (PTSD) and
      posttraumatic stress symptoms (PSS) for children and adolescents. METHODS: We
      reviewed broad-based child mental health journals within the disciplines of
      pediatrics, child psychology, and trauma, from 1995 to 2004, to identify measures
      of PTSD and PSS for children and adolescents. The review includes a summary of
      the psychometric properties and associated features of the measures and the
      clinical domains and types of studies using each measure. RESULTS: Seven measures
      of PTSD and PSS were identified, including clinician-administered interviews and
      self-report questionnaires. Sixty-five articles containing the measures were
      categorized into eight trauma domains. We found there is little consensus over
      measures used within each trauma domain. CONCLUSIONS: Few measures of PTSD and
      PSS have been designed specifically for young people. Further directions for
      measurement of PTSD in this age group are discussed to prevent under-diagnosis
      and under-treatment for youth.

PMID- 15947120
TI  - Scientists focus on pharmacogenomics at FDA Science Forum.

PMID- 15947121
TI  - Government leadership, investment crucial to health care's IT success.

PMID- 15947122
TI  - Quality of Medicare services a mixed picture, experts say.

PMID- 15947124
TI  - Prevention and treatment of postoperative nausea and vomiting.
AB  - PURPOSE: The physiology, risk factors, and prevention and treatment of
      postoperative nausea and vomiting (PONV) are discussed. SUMMARY: Factors to
      consider when determining a patient's risk for PONV include sex, history of PONV,
      history of motion sickness, smoking status, duration of anesthesia, use of
      opioids, and type of surgery. Receptors that, when activated, can cause nausea or
      vomiting or both include dopamine type 2, serotonin type 3, histamine type 1, and
      muscarinic cholinergic type 1 receptors. Patients at moderate to high risk for
      PONV benefit from the administration of a prophylactic antiemetic agent that
      blocks one or more of these receptors. Effective agents include transdermal
      scopolamine, prochlorperazine, promethazine, droperidol, ondansetron, dolasetron,
      granisetron, and dexamethasone. In high-risk patients, combining two or more
      antiemetics with different mechanisms of action has been shown to be more
      effective than using a single agent. In addition to administering a prophylactic
      antiemetic, it is important to reduce the patient's risk by considering regional
      anesthesia, considering inducing and maintaining general anesthesia with
      propofol, ensuring good intravenous hydration, avoiding hypotension, and
      providing effective analgesia. If PONV occurs in the immediate postoperative
      period, it is best treated with an antiemetic agent from a pharmacologic class
      different from that of the prophylactic agent. CONCLUSION: Prophylactic
      antiemetic therapy for PONV is effective, but combinations of agents may be
      necessary for high-risk patients. Nonpharmacologic strategies are also important.

PMID- 15947126
TI  - Tiotropium: an inhaled anticholinergic for chronic obstructive pulmonary disease.
AB  - PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects,
      drug interactions, dosage and administration, and formulary considerations of
      tiotropium are discussed. SUMMARY: Tiotropium, a long-acting inhaled
      anticholinergic, recently received approval from the Food and Drug Administration
      for the management of chronic obstructive pulmonary disease (COPD). In patients
      with COPD, increased parasympathetic nervous system activity leads to
      bronchoconstriction and mucus secretion. Tiotropium induces relaxation of the
      airway smooth muscle, as does ipratropium, but differs in receptor association
      and dissociation rates, allowing for once-daily administration. After inhalation,
      tiotropium reaches maximal plasma concentrations within five minutes, but
      clinical improvements in forced expiratory volume in one second (FEV(1)) are
      maintained over 24 hours. Clinical trials of tiotropium with placebo,
      ipratropium, and salmeterol have demonstrated the efficacy of tiotropium in
      improving FEV(1) and forced vital capacity values and health-related quality of
      life. The most commonly observed adverse effect is dry mouth. No increase in
      adverse effects was observed when tiotropium was administered concomitantly with
      other drugs for COPD, including sympathomimetic bronchodilators and oral and
      inhaled corticosteroids. The combination of tiotropium and other anticholinergics
      has not been studied and is not recommended. The recommended dosage of tiotropium
      is the inhalation of an 18-mug capsule with a HandiHaler breath-actuated
      inhalation device once daily. CONCLUSION: Tiotropium appears to be at least as
      effective as currently available alternatives in the treatment of patients with
      COPD who require daily bronchodilator treatment. Its simplified dosing and
      tolerable adverse-effect profile can potentially lead to enhanced patient
      compliance.

PMID- 15947127
TI  - Blueprint for implementing USP chapter 797 for compounding sterile preparations.
AB  - PURPOSE: Guidelines for adopting and successfully implementing the requirements
      of the United States Pharmacopeia (USP) chapter 797 for compounding sterile
      preparations are presented. SUMMARY: The quality of a compounded sterile
      preparation (CSP) is directly related to the methods used to ensure that the CSP
      achieves the desired goal of purity, potency, and sterility. A properly designed,
      constructed, and maintained cleanroom contributes to the quality of CSPs. Design
      criteria of a sample clean-room are supplied, as are a summary and comparison of
      the liquid disinfectants that can be used to clean and sanitize the facility and
      maintain environmental controls. All activities associated with cleaning the
      cleanroom, including air and surface sampling, must be properly documented in
      logs, examples of which are provided. A robust employee-training program for
      properly teaching aseptic technique and a method to verify that personnel have
      successfully completed the program are integral to compliance with chapter 797
      and thoroughly discussed herein. Emerging compounding and testing technology is
      also discussed. CONCLUSION: Although the task of compliance with the requirements
      of USP chapter 797 may appear overwhelming, complicated, expensive, and even
      unattainable, quality can be established via a methodical and organized approach.
      After the systems have been implemented, maintaining them requires vigilance and
      follow-up. Compliance with chapter 797 involves up-front and ongoing costs
      associated with establishing these systems, but the time, energy, and cost
      required to maintain them are far less than those of retrospective or manual
      systems of collecting, reviewing, and collating quality assurance data on a
      monthly basis.

PMID- 15947128
TI  - Pharmacists in the Omaha Metropolitan Medical Response System.
AB  - PURPOSE: The role of pharmacists in the Metropolitan Medical Response System
      (MMRS) for Omaha, Nebraska, is described. SUMMARY: Pharmacists have been involved
      in the Omaha MMRS since its inception in 2000. The Omaha MMRS has a pharmacy
      committee composed of pharmacists from local hospitals, community pharmacies, and
      two pharmacy schools. The pharmacy committee oversees the stock of
      pharmaceuticals available to Omaha in an emergency by continuously monitoring
      hospital inventories and working with state and federal planners. Pharmacists are
      responsible for planning for the receiving, staging, storing, distributing, and
      dispensing of the large quantities of pharmaceuticals that might be required in a
      disaster. Pharmacists also educate other health care professionals and the public
      about threats. CONCLUSION: Pharmacists play a major role in emergency
      preparedness in the Omaha metropolitan area and would be active participants in
      the community's response to a disaster.

PMID- 15947129
TI  - Compatibility of tramadol hydrochloride injection with selected drugs and
      solutions.

PMID- 15947130
TI  - 2004 ASHP Leadership Conference on Pharmacy Practice Management Executive
      Summary: improving patient care and medication safety.

PMID- 15947131
TI  - Motivational interviewing: a tool to improve medication adherence?

PMID- 15947132
TI  - MSH2 missense mutations alter cisplatin cytotoxicity and promote cisplatin
      induced genome instability.
AB  - Defects in the mismatch repair protein MSH2 cause tolerance to DNA damage. We
      report how cancer-derived and polymorphic MSH2 missense mutations affect
      cisplatin cytotoxicity. The chemotolerance phenotype was compared with the
      mutator phenotype in a yeast model system. MSH2 missense mutations display a
      strikingly different effect on cell death and genome instability. A mutator
      phenotype does not predict chemotolerance or vice versa. MSH2 mutations that were
      identified in tumors (Y109C) or as genetic variations (L402F) promote tolerance
      to cisplatin, but leave the initial mutation rate of cells unaltered. A secondary
      increase in the mutation rate is observed after cisplatin exposure in these
      strains. The mutation spectrum of cisplatin-resistant mutators identifies
      persistent cisplatin adduction as the cause for this acquired genome instability.
      Our results demonstrate that MSH2 missense mutations that were identified in
      tumors or as polymorphic variations can cause increased cisplatin tolerance
      independent of an initial mutator phenotype. Cisplatin exposure promotes drug
      induced genome instability. From a mechanistical standpoint, these data
      demonstrate functional separation between MSH2-dependent cisplatin cytotoxicity
      and repair. From a clinical standpoint, these data provide valuable information
      on the consequences of point mutations for the success of chemotherapy and the
      risk for secondary carcinogenesis.

PMID- 15947133
TI  - Gene targeting using randomly inserted group II introns (targetrons) recovered
      from an Escherichia coli gene disruption library.
AB  - The Lactococcus lactis Ll.LtrB group II intron retrohomes by reverse-splicing
      into one strand of a double-stranded DNA target site, while the intron-encoded
      protein cleaves the opposite strand and uses it to prime reverse transcription of
      the inserted intron RNA. The protein and intron RNA function in a
      ribonucleoprotein particle, with much of the DNA target sequence recognized by
      base-pairing of the intron RNA. Consequently, group II introns can be
      reprogrammed to insert into specific or random DNA sites by substituting specific
      or random nucleotide residues in the intron RNA. Here, we show that an
      Escherichia coli gene disruption library obtained using such randomly inserting
      Ll.LtrB introns contains most viable E.coli gene disruptions. Further, each
      inserted intron is targeted to a specific site by its unique base-pairing
      regions, and in most cases, could be recovered by PCR and used unmodified to
      obtain the desired single disruptant. Additionally, we identified a subset of
      introns that insert at sites lacking T+5, a nucleotide residue critical for
      second-strand cleavage. All such introns tested individually gave the desired
      specific disruption, some by switching to an alternate retrohoming mechanism
      targeting single-stranded DNA and using a nascent lagging DNA strand to prime
      reverse transcription.

PMID- 15947134
TI  - A real-time semi-quantitative RT-PCR assay demonstrates that the pilE sequence
      dictates the frequency and characteristics of pilin antigenic variation in
      Neisseria gonorrhoeae.
AB  - A semi-quantitative real-time RT-PCR assay was designed to measure gonococcal
      pilin antigenic variation (SQ-PCR Av assay). This assay employs 17 hybridization
      probe sets that quantitate subpopulations of pilin transcripts carrying different
      silent pilin copy sequences and one set that detects total pilE transcript
      levels. Mixtures of a DNA standard carrying the silent copy being detected and a
      clone encoding the starting pilE sequence, which is the majority pilE template,
      provided amplification curves that closely matched the experimental data and
      allowed an analysis of the contribution of different silent pilin copies to
      variation. The SQ-PCR Av assay was verified using DNA sequence analysis to
      demonstrate that this methodology allowed an accurate analysis of pilin
      variation. Both assays showed that with a specific starting pilE sequence, only a
      subset of the silent pilin copies recombine into pilE at a detectable level, and
      that this limited subset was reproducibly detected in replicate cultures. When an
      isogenic pilE sequence variant was examined using both assays, a new subset of
      silent copy sequences were detected recombining into pilE and the overall
      frequency of variation was increased. Thus, the parental pilE sequence influences
      the frequency of variation and the repertoire of pilin variants produced.

PMID- 15947135
TI  - A spontaneous tRNA suppressor of a mutation in the Chlamydomonas reinhardtii
      nuclear MCD1 gene required for stability of the chloroplast petD mRNA.
AB  - Numerous nuclear gene products are required for the correct expression of
      organellar genes. One such gene in the green alga Chlamydomonas reinhardtii is
      MCD1, whose product is required for stability of the chloroplast-encoded petD
      mRNA. In mcd1 mutants, which are non-photosynthetic, petD mRNA is degraded by a
      5'-3' exonuclease activity, resulting in a failure to synthesize its product,
      subunit IV of the cytochrome b (6)/f complex. Here, we report the sequence of the
      wild-type MCD1 gene, which encodes a large and novel putative protein. Analysis
      of three mutant alleles showed that two harbored large deletions, but that one
      allele, mcd1-2, had a single base change resulting in a nonsense codon near the N
      terminus. This same mutant allele can be suppressed by a second-site mutation in
      the nuclear MCD2 gene, whereas mcd2-1 cannot suppress the deletion in mcd1-1
      (Esposito,D. Higgs,D.C. Drager,R.G. Stern, D.B. and Girard-Bascou,J. (2001) Curr.
      Genet., 39, 40-48). We report the cloning of mcd2-1, and show that the mutation
      lies in a tRNA(Ser)(CGA), which has been modified to translate the nonsense codon
      in mcd1-2. We discuss how the existence of a large tRNA(Ser) gene family may
      permit this suppression without pleiotropic consequences.

PMID- 15947136
TI  - RNA polymerase II is required for RNAi-dependent heterochromatin assembly.
AB  - In Schizosaccharomyces pombe, the RNA interference (RNAi) machinery converts
      pericentromeric transcripts into small interfering RNAs (siRNAs) and is required
      for the assembly of pericentromeric heterochromatin. Here we describe a mutation
      in the second largest subunit of RNA polymerase II (RNAPII). Both wild-type and
      mutant RNAPII localized to the pericentromere. However, the mutation resulted in
      the loss of heterochromatic histone modifications and in the accumulation of
      pericentromeric transcripts, accompanied by the loss of siRNAs. This phenotype
      resembles mutants in RNAi and suggests that RNAPII couples pericentromeric
      transcription with siRNA processing and heterochromatin assembly.

PMID- 15947138
TI  - Heat flux anomalies in Antarctica revealed by satellite magnetic data.
AB  - The geothermal heat flux is an important factor in the dynamics of ice sheets; it
      affects the occurrence of subglacial lakes, the onset of ice streams, and mass
      losses from the ice sheet base. Because direct heat flux measurements in ice
      covered regions are difficult to obtain, we developed a method that uses
      satellite magnetic data to estimate the heat flux underneath the Antarctic ice
      sheet. We found that the heat flux underneath the ice sheet varies from 40 to 185
      megawatts per square meter and that areas of high heat flux coincide with known
      current volcanism and some areas known to have ice streams.

PMID- 15947137
TI  - Complete replication of hepatitis C virus in cell culture.
AB  - Many aspects of the hepatitis C virus (HCV) life cycle have not been reproduced
      in cell culture, which has slowed research progress on this important human
      pathogen. Here, we describe a full-length HCV genome that replicates and produces
      virus particles that are infectious in cell culture (HCVcc). Replication of HCVcc
      was robust, producing nearly 10(5) infectious units per milliliter within 48
      hours. Virus particles were filterable and neutralized with a monoclonal antibody
      against the viral glycoprotein E2. Viral entry was dependent on cellular
      expression of a putative HCV receptor, CD81. HCVcc replication was inhibited by
      interferon-alpha and by several HCV-specific antiviral compounds, suggesting that
      this in vitro system will aid in the search for improved antivirals.

PMID- 15947140
TI  - Wanted: women in clinical trials.

PMID- 15947139
TI  - Ant nestmate and non-nestmate discrimination by a chemosensory sensillum.
AB  - In animal societies, chemical communication plays an important role in conflict
      and cooperation. For ants, cuticular hydrocarbon (CHC) blends produced by non
      nestmates elicit overt aggression. We describe a sensory sensillum on the
      antennae of the carpenter ant Camponotus japonicus that functions in nestmate
      discrimination. This sensillum is multiporous and responds only to non-nestmate
      CHC blends. This suggests a role for a peripheral recognition mechanism in
      detecting colony-specific chemical signals.

PMID- 15947141
TI  - Science and society. Smithsonian gives grudging ok to film backing ID argument.

PMID- 15947142
TI  - U.S. science budget. VA asked to bolster mental health research.

PMID- 15947143
TI  - Psychology. Survey finds U.S. mental health holds steady.

PMID- 15947145
TI  - Climate change. California sets goals for cutting greenhouse gases.

PMID- 15947144
TI  - Proteomics. Canadian global database may move to Singapore after loss of funding.

PMID- 15947146
TI  - European Union. Researchers lobby to head off threatened cuts.

PMID- 15947147
TI  - Microbiology. Mosquito-killing fungi may join the battle against malaria.

PMID- 15947148
TI  - Genetics. In voles, a little extra DNA makes for faithful mates.

PMID- 15947149
TI  - Cell biology. Ready or not? Human ES cells head toward the clinic.

PMID- 15947150
TI  - Cell biology. Still waiting their turn.

PMID- 15947151
TI  - Cell biology. Human embryonic stem cells may be toxicology's new best friends.

PMID- 15947152
TI  - Virology. Culture systems for hepatitis C virus in sight at last.

PMID- 15947153
TI  - Physiology. Science in the 'death zone'.

PMID- 15947154
TI  - High-energy physics. KEK researchers catch glimpse of outlandish particles.

PMID- 15947155
TI  - The question of forbidden knowledge.

PMID- 15947156
TI  - The problems of radiocarbon dating.

PMID- 15947157
TI  - Comment on "Thymic origin of intestinal alphabeta T cells revealed by fate
      mapping of RORgammat+ cells".

PMID- 15947159
TI  - Public health. Pharmacist refusals: a threat to women's health.

PMID- 15947160
TI  - Public health. Conscientious objection and the pharmacist.

PMID- 15947161
TI  - Biomedicine. Asthmatics breathe easier when it's SNO-ing.

PMID- 15947162
TI  - Applied physics. Nanoantennas for light emission.

PMID- 15947164
TI  - Psychology. Appearance DOES matter.

PMID- 15947163
TI  - Immunology. Opposites attract in differentiating T cells.

PMID- 15947165
TI  - Materials science. Snapshots of crystal growth.

PMID- 15947167
TI  - From dearth to deluge.

PMID- 15947168
TI  - Clinical trials: keeping score on the sexes.

PMID- 15947169
TI  - Gender in the pharmacy: does it matter?

PMID- 15947170
TI  - Sex and the suffering brain.

PMID- 15947171
TI  - Poor countries, added perils for women.

PMID- 15947172
TI  - Let's talk about sex--and drugs.

PMID- 15947173
TI  - Bone quality fills holes in fracture risk.

PMID- 15947174
TI  - HIV/AIDS in women: an expanding epidemic.
AB  - More than 20 years into the human immunodeficiency virus-type 1 (HIV-1) epidemic,
      women account for nearly half of the 40 million people living with HIV-1
      worldwide, with an even higher proportion existing in developing countries.
      Social determinants of female vulnerability to HIV-1 include gender disparities,
      poverty, cultural and sexual norms, lack of education, and violence. Women are
      also more susceptible to HIV-1 because of hormonal changes, vaginal microbial
      ecology and physiology, and a higher prevalence of sexually transmitted diseases.
      Prevention strategies must address the wide range of gender inequalities that
      promote the dissemination of HIV-1.

PMID- 15947175
TI  - Molecular and cellular basis of cardiovascular gender differences.
AB  - Cardiovascular diseases (CVDs), the major cause of morbidity and mortality for
      both men and women, occur uncommonly in premenopausal women, but their incidence
      rises sharply after the menopausal transition. Cardiovascular gender differences
      are apparent long before CVDs appear in men and women, and improved understanding
      of the biology underlying these differences has the potential to advance the
      diagnosis and treatment of CVDs in both sexes. This review considers gender
      differences in the molecular and cellular physiology of the heart and blood
      vessels in health and disease, highlighting understudied areas that can help
      resolve the current controversy regarding hormone replacement therapy and improve
      cardiovascular health in women.

PMID- 15947176
TI  - The pains of endometriosis.
AB  - Endometriosis is a disease defined by the presence of endometrial tissue outside
      of the uterus. Severe pelvic pain is often associated with endometriosis, and
      this pain can be diminished with therapies that suppress estrogen production.
      Many women with endometriosis also suffer from other chronic pain conditions.
      Recent studies suggest that mechanisms underlying these pains and sensitivity to
      estrogen involve the growth into the ectopic endometrial tissue of a nerve
      supply, which could have a varied and widespread influence on the activity of
      neurons throughout the central nervous system.

PMID- 15947177
TI  - Uterine fibroids: the elephant in the room.
AB  - Uterine fibroids (leiomyomas) have historically been viewed as important chiefly
      as the major indication for hysterectomy. As new therapies are developed, the
      heterogeneity of this disease becomes therapeutically relevant. An awareness of
      the role of genetics, the extracellular matrix, and hormones in tumor etiology is
      key to understanding this disease.

PMID- 15947178
TI  - Latest advances in understanding preeclampsia.
AB  - Preeclampsia is a relatively common pregnancy disorder that originates in the
      placenta and causes variable maternal and fetal problems. In the worst cases, it
      may threaten the survival of both mother and baby. We summarize recent work on
      the causes of preeclampsia, which reveals a new mode of maternal immune
      recognition of the fetus, relevant to the condition. The circulating factors
      derived from the placenta, which contributes to the clinical syndrome, are now
      better understood. This brief review on preeclampsia does not cover all aspects
      of this intriguing condition but focuses on some new and interesting findings.

PMID- 15947179
TI  - Observations by the international tsunami survey team in Sri Lanka.
AB  - In response to the 26 December 2004 tsunami, a survey team of scientists was
      dispatched to Sri Lanka. Measurements made by the team show that the tsunami
      elevation and runup ranged from 5 to 12 meters. Eyewitnesses report that up to
      three separate waves attacked the coast, with the second or third generally the
      largest. Our conclusion stresses the importance of education: Residents with a
      basic knowledge of tsunamis, as well as an understanding of how environmental
      modifications will affect overland flow, are paramount to saving lives and
      minimizing tsunami destruction.

PMID- 15947180
TI  - Field data and satellite imagery of tsunami effects in Banda Aceh.
AB  - After the 26 December 2004 earthquake and tsunami, field data on the extent of
      the inundation in Banda Aceh, Sumatra, were combined with satellite imagery to
      quantify the tsunami effects. Flow depths along the shores of Banda Aceh exceeded
      9 meters, with inundation reaching 3 to 4 kilometers inland. To the southwest, at
      Lhoknga, flow depths were more than 15 meters at the shoreline and runup exceeded
      25 meters. Erosion and subsidence moved the shoreline of Banda Aceh inland up to
      1.5 kilometers, and 65 square kilometers of land between Banda Aceh and Lhoknga
      were flooded.

PMID- 15947181
TI  - Infrared echoes near the supernova remnant Cassiopeia A.
AB  - Two images of Cassiopeia A obtained at 24 micrometers with the Spitzer Space
      Telescope over a 1-year time interval show moving structures outside the shell of
      the supernova remnant to a distance of more than 20 arc minutes. Individual
      features exhibit apparent motions of 10 to 20 arc seconds per year, independently
      confirmed by near-infrared observations. The observed tangential velocities are
      at roughly the speed of light. It is likely that the moving structures are
      infrared echoes, in which interstellar dust is heated by the explosion and by
      flares from the compact object near the center of the remnant.

PMID- 15947182
TI  - Resonant optical antennas.
AB  - We have fabricated nanometer-scale gold dipole antennas designed to be resonant
      at optical frequencies. On resonance, strong field enhancement in the antenna
      feed gap leads to white-light supercontinuum generation. The antenna length at
      resonance is considerably shorter than one-half the wavelength of the incident
      light. This is in contradiction to classical antenna theory but in qualitative
      accordance with computer simulations that take into account the finite metallic
      conductivity at optical frequencies. Because optical antennas link propagating
      radiation and confined/enhanced optical fields, they should find applications in
      optical characterization, manipulation of nanostructures, and optical information
      processing.

PMID- 15947183
TI  - Giant larvacean houses: rapid carbon transport to the deep sea floor.
AB  - An unresolved issue in ocean science is the discrepancy between the food
      requirements of the animals living on the deep sea floor and their food supply,
      as measured by sediment traps. A 10-year time-series study of the water column
      off Monterey Bay, California, revealed that the discarded mucus feeding
      structures of giant larvaceans carry a substantial portion of the upper ocean's
      productivity to the deep seabed. These abundant, rapidly sinking, carbon-rich
      vectors are not detected by conventional sampling methods and thus have not been
      included in calculations of vertical nutrient flux or in oceanic carbon budgets.

PMID- 15947184
TI  - Rapid acidification of the ocean during the Paleocene-Eocene thermal maximum.
AB  - The Paleocene-Eocene thermal maximum (PETM) has been attributed to the rapid
      release of approximately 2000 x 10(9) metric tons of carbon in the form of
      methane. In theory, oxidation and ocean absorption of this carbon should have
      lowered deep-sea pH, thereby triggering a rapid (<10,000-year) shoaling of the
      calcite compensation depth (CCD), followed by gradual recovery. Here we present
      geochemical data from five new South Atlantic deep-sea sections that constrain
      the timing and extent of massive sea-floor carbonate dissolution coincident with
      the PETM. The sections, from between 2.7 and 4.8 kilometers water depth, are
      marked by a prominent clay layer, the character of which indicates that the CCD
      shoaled rapidly (<10,000 years) by more than 2 kilometers and recovered gradually
      (>100,000 years). These findings indicate that a large mass of carbon (>>2000 x
      10(9) metric tons of carbon) dissolved in the ocean at the Paleocene-Eocene
      boundary and that permanent sequestration of this carbon occurred through
      silicate weathering feedback.

PMID- 15947185
TI  - Photoinduced plasticity in cross-linked polymers.
AB  - Chemically cross-linked polymers are inherently limited by stresses that are
      introduced by post-gelation volume changes during polymerization. It is also
      difficult to change a cross-linked polymer's shape without a corresponding loss
      of material properties or substantial stress development. We demonstrate a cross
      linked polymer that, upon exposure to light, exhibits stress and/or strain
      relaxation without any concomitant change in material properties. This result is
      achieved by introducing radicals via photocleavage of residual photoinitiator in
      the polymer matrix, which then diffuse via addition-fragmentation chain transfer
      of midchain functional groups. These processes lead to photoinduced plasticity,
      actuation, and equilibrium shape changes without residual stress. Such polymeric
      materials are critical to the development of microdevices, biomaterials, and
      polymeric coatings.

PMID- 15947186
TI  - Trophic cascades in a formerly cod-dominated ecosystem.
AB  - Removal of top predators from ecosystems can result in cascading effects through
      the trophic levels below, completely restructuring the food web. Cascades have
      been observed in small-scale or simple food webs, but not in large, complex, open
      ocean ecosystems. Using data spanning many decades from a once cod-dominated
      northwest Atlantic ecosystem, we demonstrate a trophic cascade in a large marine
      ecosystem. Several cod stocks in other geographic areas have also collapsed
      without recovery, suggesting the existence of trophic cascades in these systems.

PMID- 15947187
TI  - Inferences of competence from faces predict election outcomes.
AB  - We show that inferences of competence based solely on facial appearance predicted
      the outcomes of U.S. congressional elections better than chance (e.g., 68.8% of
      the Senate races in 2004) and also were linearly related to the margin of
      victory. These inferences were specific to competence and occurred within a 1
      second exposure to the faces of the candidates. The findings suggest that rapid,
      unreflective trait inferences can contribute to voting choices, which are widely
      assumed to be based primarily on rational and deliberative considerations.

PMID- 15947188
TI  - Microsatellite instability generates diversity in brain and sociobehavioral
      traits.
AB  - Repetitive microsatellites mutate at relatively high rates and may contribute to
      the rapid evolution of species-typical traits. We show that individual alleles of
      a repetitive polymorphic microsatellite in the 5' region of the prairie vole
      vasopressin 1a receptor (avpr1a) gene modify gene expression in vitro. In vivo,
      we observe that this regulatory polymorphism predicts both individual differences
      in receptor distribution patterns and socio-behavioral traits. These data suggest
      that individual differences in gene expression patterns may be conferred via
      polymorphic microsatellites in the cis-regulatory regions of genes and may
      contribute to normal variation in behavioral traits.

PMID- 15947189
TI  - Fungal pathogen reduces potential for malaria transmission.
AB  - Using a rodent malaria model, we found that exposure to surfaces treated with
      fungal entomopathogens following an infectious blood meal reduced the number of
      mosquitoes able to transmit malaria by a factor of about 80. Fungal infection,
      achieved through contact with both solid surfaces and netting for durations well
      within the typical post-feed resting periods, was sufficient to cause >90%
      mortality. Daily mortality rates escalated dramatically around the time of
      sporozoite maturation, and infected mosquitoes showed reduced propensity to blood
      feed. Residual sprays of fungal biopesticides might replace or supplement
      chemical insecticides for malaria control, particularly in areas of high
      insecticide resistance.

PMID- 15947190
TI  - An entomopathogenic fungus for control of adult African malaria mosquitoes.
AB  - Biological control of malaria mosquitoes in Africa has rarely been used in vector
      control programs. Recent developments in this field show that certain fungi are
      virulent to adult Anopheles mosquitoes. Practical delivery of an entomopathogenic
      fungus that infected and killed adult Anopheles gambiae, Africa's main malaria
      vector, was achieved in rural African village houses. An entomological
      inoculation rate model suggests that implementation of this vector control
      method, even at the observed moderate coverage during a field study in Tanzania,
      would significantly reduce malaria transmission intensity.

PMID- 15947191
TI  - A cysteine-rich extracellular protein containing a PA14 domain mediates quorum
      sensing in Dictyostelium discoideum.
AB  - Much remains to be understood about quorum-sensing factors that allow cells to
      sense their local density. Dictyostelium discoideum is a simple eukaryote that
      grows as single-celled amoebae and switches to multicellular development when
      food becomes limited. As the growing cells reach a high density, they begin
      expressing discoidin genes. The cells secrete an unknown factor, and at high cell
      densities the concomitant high levels of the factor induce discoidin expression.
      We report here the enrichment of discoidin-inducing complex (DIC), an
      approximately 400-kDa protein complex that induces discoidin expression during
      growth and development. Two proteins in the DIC preparation, DicA1 and DicB, were
      identified by sequencing proteolytic digests. DicA1 and DicB were expressed in
      Escherichia coli and tested for their ability to induce discoidin during growth
      and development. Recombinant DicB was unable to induce discoidin expression,
      while recombinant DicA1 was able to induce discoidin expression. This suggests
      that DicA1 is an active component of DIC and indicates that posttranslational
      modification is dispensable for activity. DicA1 mRNA is expressed in vegetative
      and developing cells. The mature secreted form of DicA1 has a molecular mass of
      80 kDa and has a 24-amino-acid cysteine-rich repeat that is similar to repeats in
      Dictyostelium proteins, such as the extracellular matrix protein ecmB/PstA, the
      prespore cell-inducing factor PSI, and the cyclic AMP phosphodiesterase inhibitor
      PDI. Together, the data suggest that DicA1 is a component of a secreted quorum
      sensing signal regulating discoidin gene expression during Dictyostelium growth
      and development.

PMID- 15947192
TI  - The RIM101/pacC homologue from the basidiomycete Ustilago maydis is functional in
      multiple pH-sensitive phenomena.
AB  - A homologue of the gene encoding the transcription factor Rim101 (PacC), involved
      in pH signal transduction in fungi, was identified in the pathogenic
      basidiomycete Ustilago maydis. The gene (RIM101) encodes a protein of 827 amino
      acid residues, which shows highest similarity to PacC proteins from Fusarium
      oxysporum and Aspergillus niger. The gene had the capacity to restore protease
      activity to rim101 mutants from Yarrowia lipolytica, confirming its homologous
      function, and was expressed at both acid and neutral pH. Null Deltarim101 mutants
      were not affected in the in vitro pH-induced dimorphic transition, their growth
      rate, resistance to hypertonic sorbitol or KCl stress, and pathogenicity.
      However, similar to pacC (rim101) mutants in other fungi, they displayed a
      pleiotropic phenotype with alterations in morphogenesis, impairment in protease
      secretion, and increased sensitivity to Na+ and Li+ ions. Other phenotypic
      characteristics not previously reported in fungal pacC (rim101) mutants
      (morphological changes, increased sensitivity to lytic enzymes, and augmented
      polysaccharide secretion) were also observed in U. maydis mutants. All these
      modifications were alleviated by transformation with the wild-type gene,
      confirming that all were the result of mutation in RIM101. These data indicate
      that the Pal/Rim pathway is functional in U. maydis (and probably in other
      basidiomycetes) and plays complex roles in pH-sensing phenomena, as occurs in
      ascomycetes and deuteromycetes.

PMID- 15947193
TI  - A genome sequence survey shows that the pathogenic yeast Candida parapsilosis has
      a defective MTLa1 allele at its mating type locus.
AB  - Candida parapsilosis is responsible for ca. 15% of Candida infections and is of
      particular concern in neonates and surgical intensive care patients. The related
      species Candida albicans has recently been shown to possess a functional mating
      pathway. To analyze the analogous pathway in C. parapsilosis, we carried out a
      genome sequence survey of the type strain. We identified ca. 3,900 genes, with an
      average amino acid identity of 59% with C. albicans. Of these, 23 are predicted
      to be predominantly involved in mating. We identified a genomic locus homologous
      to the MTLa mating type locus of C. albicans, but the C. parapsilosis type strain
      has at least two internal stop codons in the MTLa1 open reading frame, and two
      predicted introns are not spliced. These stop codons were present in MTLa1 of all
      eight C. parapsilosis isolates tested. Furthermore, we found that all isolates of
      C. parapsilosis tested appear to contain only the MTLa idiomorph at the
      presumptive mating locus, unlike C. albicans and C. dubliniensis. MTLalpha
      sequences are present but at a different chromosomal location. It is therefore
      likely that all (or at least the majority) of C. parapsilosis isolates have a
      mating pathway that is either defective or substantially different from that of
      C. albicans.

PMID- 15947194
TI  - ACE2, CBK1, and BUD4 in budding and cell separation.
AB  - Mutations in the RAM network genes, including CBK1, MOB2, KIC1, HYM1, and TAO3,
      cause defects in bud site selection, asymmetric apical growth, and mating
      projections. Additionally, these mutants show altered colony morphology, cell
      separation defects, and reduced CTS1 expression, phenotypes also seen by mutating
      the Ace2 transcription factor. We show that an ACE2 multicopy plasmid suppresses
      the latter three defects of RAM network mutations, demonstrating that Ace2 is
      downstream of the RAM network and suggesting that these phenotypes are caused by
      reduced expression of Ace2 target genes. We show that wild-type W303 strains have
      a bud4 mutation and that combining bud4 with either ace2 or cbk1 in haploids
      results in altered colony morphology. We describe a timed sedimentation assay
      that allows quantitation of cytokinesis defects and subtle changes in budding
      pattern and cell shape. Experiments examining budding patterns and sedimentation
      rates both show that Ace2 and Cbk1 have independent functions in addition to
      their common pathway in transcription of genes such as CTS1. SWI5 encodes a
      transcription factor paralogous to ACE2. Additive effects are seen in cbk1 swi5
      strains, and we show that activation of some target genes, such as EGT2, requires
      either Swi5 or Ace2 with Cbk1. The relative roles and interactions of Ace2, Cbk1,
      and Bud4 in bud site selection, polarized growth, and cell separation are
      discussed.

PMID- 15947195
TI  - A novel assay for protein phosphatase 2A (PP2A) complexes in vivo reveals
      differential effects of covalent modifications on different Saccharomyces
      cerevisiae PP2A heterotrimers.
AB  - Protein phosphatase 2A (PP2A) catalytic subunit can be covalently modified at its
      carboxy terminus by phosphorylation or carboxymethylation. Determining the
      effects of these covalent modifications on the relative amounts and functions of
      different PP2A heterotrimers is essential to understanding how these
      modifications regulate PP2A-controlled cellular processes. In this study we have
      validated and used a novel in vivo assay for assessing PP2A heterotrimer
      formation in Saccharomyces cerevisiae: the measurement of heterotrimer-dependent
      localization of green fluorescent protein-PP2A subunits. This assay relies on the
      fact that the correct cellular localization of PP2A requires that it be fully
      assembled. Thus, reduced localization would occur as the result of the inability
      to assemble a stable heterotrimer. Using this assay, we determined the effects of
      PP2A C-subunit phosphorylation mimic mutations and reduction or loss of PP2A
      methylation on the formation and localization of PP2A(B/Cdc55p) and
      PP2A(B'/Rts1p) heterotrimers. Collectively, our findings demonstrate that
      phosphorylation and methylation of the PP2A catalytic subunit can influence its
      function both by regulating the total amount of specific PP2A heterotrimers
      within a cell and by altering the relative proportions of PP2A(B/Cdc55p) and
      PP2A(B'/Rts1p) heterotrimers up to 10-fold. Thus, these posttranslational
      modifications allow flexible, yet highly coordinated, regulation of PP2A
      dependent signaling pathways that in turn modulate cell growth and function.

PMID- 15947196
TI  - Ability of Sit4p to promote K+ efflux via Nha1p is modulated by Sap155p and
      Sap185p.
AB  - We demonstrate here that SAP155 encodes a negative modulator of K+ efflux in the
      yeast Saccharomyces cerevisiae. Overexpression of SAP155 decreases efflux,
      whereas deletion increases efflux. In contrast, a homolog of SAP155, called
      SAP185, encodes a positive modulator of K+ efflux: overexpression of SAP185
      increases efflux, whereas deletion decreases efflux. Two other homologs, SAP4 and
      SAP190, are without effect on K+ homeostasis. Both SAP155 and SAP185 require the
      presence of SIT4 for function, which encodes a PP2A-like phosphatase important
      for the G1-S transition through the cell cycle. Overexpression of either the
      outwardly rectifying K+ channel, Tok1p, or the putative plasma membrane K+/H+
      antiporter, Kha1p, increases efflux in both wild-type and sit4Delta strains.
      However, overexpression of the Na+-K+/H+ antiporter, Nha1p, is without effect in
      a sit4Delta strain, suggesting that Sit4p signals to Nha1p. In summary, the
      combined activities of Sap155p and Sap185p appear to control the function of
      Nha1p in K+ homeostasis via Sit4p.

PMID- 15947197
TI  - Saccharomyces cerevisiae heat shock transcription factor regulates cell wall
      remodeling in response to heat shock.
AB  - The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae
      regulates expression of genes encoding heat shock proteins and a variety of other
      proteins as well. To better understand the cellular roles of Hsf1, we screened
      multicopy suppressor genes of a temperature-sensitive hsf1 mutation. The RIM15
      gene, encoding a protein kinase that is negatively regulated by the cyclic AMP
      dependent protein kinase, was identified as a suppressor, but Rim15-regulated
      stress-responsive transcription factors, such as Msn2, Msn4, and Gis1, were
      unable to rescue the temperature-sensitive growth phenotype of the hsf1 mutant.
      Another class of suppressors encoded cell wall stress sensors, Wsc1, Wsc2, and
      Mid2, and the GDP/GTP exchange factor Rom2 that interacts with these cell wall
      sensors. Activation of a protein kinase, Pkc1, which is induced by these cell
      wall sensor proteins upon heat shock, but not activation of the Pkc1-regulated
      mitogen-activated protein kinase cascade, was necessary for the hsf1 suppression.
      Like Wsc-Pkc1 pathway mutants, hsf1 cells exhibited an osmotic remedial cell
      lysis phenotype at elevated temperatures. Several of the other suppressors were
      found to encode proteins functioning in cell wall organization. These results
      suggest that Hsf1 in concert with Pkc1 regulates cell wall remodeling in response
      to heat shock.

PMID- 15947198
TI  - Role of integrase in reverse transcription of the Saccharomyces cerevisiae
      retrotransposon Ty1.
AB  - Reverse transcriptase (RT) with its associated RNase H (RH) domain and integrase
      (IN) are key enzymes encoded by retroviruses and retrotransposons. Several
      studies have implied a functional role of the interaction between IN and RT
      during the replication of retroviral and retrotransposon genomes. In this study,
      IN deletion mutants were used to investigate the role of IN on the RT activity of
      the yeast Saccharomyces cerevisiae retrotransposon Ty1. We have identified two
      domains of Ty1 integrase which have effects on RT activity in vivo. The deletion
      of a domain spanning amino acid residues 233 to 520 of IN increases the exogenous
      specific activity of RT up to 20-fold, whereas the removal of a region rich in
      acidic amino acid residues between residues 521 and 607 decreases its activity.
      The last result complements our observation that an active recombinant RT protein
      can be obtained if a small acidic tail mimicking the acidic domain of IN is fused
      to the RT-RH domain. We suggest that interaction between these acidic amino acid
      residues of IN and a basic region of RT could be critical for the correct folding
      of RT and for the formation of an active conformation of the enzyme.

PMID- 15947199
TI  - A Rac homolog functions downstream of Ras1 to control hyphal differentiation and
      high-temperature growth in the pathogenic fungus Cryptococcus neoformans.
AB  - The Cryptococcus neoformans Ras1 protein serves as a central regulator for
      several signaling pathways. Ras1 controls the induction of the mating pheromone
      response cascade as well as a distinct signaling pathway that allows this
      pathogenic fungus to grow at human physiological temperature. To characterize
      elements of the Ras1-dependent high-temperature growth pathway, we performed a
      multicopy suppressor screen, identifying genes whose overexpression allows the
      ras1 mutant to grow at 37 degrees C. Using this genetic technique, we identified
      a C. neoformans gene encoding a Rac homolog that suppresses multiple ras1 mutant
      phenotypes. Deletion of the RAC1 gene does not affect high-temperature growth.
      However, a rac1 mutant strain demonstrates a profound defect in haploid
      filamentation as well as attenuated mating. In a yeast two-hybrid assay, Rac1
      physically interacts with the PAK kinase Ste20, which similarly regulates hyphal
      formation in this fungus. Similar to Rac1, overexpression of the STE20alpha gene
      also restores high-temperature growth to the ras1 mutant. These results support a
      model in which the small G protein Rac1 acts downstream of Ras proteins and
      coordinately with Ste20 to control high-temperature growth and cellular
      differentiation in this human fungal pathogen.

PMID- 15947200
TI  - Calcium- and calcineurin-independent roles for calmodulin in Cryptococcus
      neoformans morphogenesis and high-temperature growth.
AB  - The function of calcium as a signaling molecule is conserved in eukaryotes from
      fungi to humans. Previous studies have identified the calcium-activated
      phosphatase calcineurin as a critical factor in governing growth of the human
      pathogenic fungus Cryptococcus neoformans at mammalian body temperature. Here, we
      employed insertional mutagenesis to identify new genes required for growth at 37
      degrees C. One insertion mutant, cam1-ts, that displayed a growth defect at 37
      degrees C and hypersensitivity to the calcineurin inhibitor FK506 at 25 degrees C
      was isolated. Both phenotypes were linked to the dominant marker in genetic
      crosses, and molecular analysis revealed that the insertion occurred in the 3'
      untranslated region of the gene encoding the calcineurin activator calmodulin
      (CAM1) and impairs growth at 37 degrees C by significantly reducing calmodulin
      mRNA abundance. The CAM1 gene was demonstrated to be essential using genetic
      analysis of a CAM1/cam1Delta diploid strain. In the absence of calcineurin
      function, the cam1-ts mutant displayed a severe morphological defect with
      impaired bud formation. Expression of a calmodulin-independent calcineurin mutant
      did not suppress the growth defect of the cam1-ts mutant at 37 degrees C,
      indicating that calmodulin promotes growth at high temperature via calcineurin
      dependent and -independent pathways. In addition, a Ca2+-binding-defective allele
      of CAM1 complemented the 37 degrees C growth defect, FK506 hypersensitivity, and
      morphogenesis defect of the cam1-ts mutant. Our findings reveal that calmodulin
      performs Ca2+- and calcineurin-independent and -dependent roles in controlling C.
      neoformans morphogenesis and high-temperature growth.

PMID- 15947201
TI  - ABG1, a novel and essential Candida albicans gene encoding a vacuolar protein
      involved in cytokinesis and hyphal branching.
AB  - Immunoscreening of a Candida albicans expression library resulted in the
      isolation of a novel gene encoding a 32.9-kDa polypeptide (288 amino acids), with
      27.7% homology to the product of Saccharomyces cerevisiae YGR106c, a putative
      vacuolar protein. Heterozygous mutants in this gene displayed an altered budding
      growth pattern, characterized by the formation of chains of buds, decreasingly in
      size towards the apex, without separation of the daughter buds. Consequently,
      this gene was designated ABG1. A conditional mutant for ABG1 with the remaining
      allele under the control of the MET3 promoter did not grow in the presence of
      methionine and cysteine, demonstrating that ABG1 was essential for viability.
      Western analysis revealed the presence of a major 32.9-kDa band, mainly in a
      particulate fraction (P40) enriched in vacuoles, and tagging with green
      fluorescent protein confirmed that Abg1p localized to the vacuole. Vacuole
      inheritance has been linked to the regulation of branching frequency in C.
      albicans. Under repressing conditions, the conditional mutant had an increased
      frequency of branching under hyphal inducing conditions and an altered
      sensitivity to substances that interfered with cell wall assembly. Repression of
      ABG1 in the conditional mutant strain caused disturbance of normal size and
      number of vacuoles both in yeast and mycelial cells and also in the asymmetric
      vacuole inheritance associated with the characteristic pattern of germ tubes and
      branching in C. albicans. These observations indicate that ABG1 plays a key role
      in vacuole biogenesis, cytokinesis, and hyphal branching.

PMID- 15947202
TI  - Contribution of horizontal gene transfer to the evolution of Saccharomyces
      cerevisiae.
AB  - The genomes of the hemiascomycetes Saccharomyces cerevisiae and Ashbya gossypii
      have been completely sequenced, allowing a comparative analysis of these two
      genomes, which reveals that a small number of genes appear to have entered these
      genomes as a result of horizontal gene transfer from bacterial sources. One
      potential case of horizontal gene transfer in A. gossypii and 10 potential cases
      in S. cerevisiae were identified, of which two were investigated further. One
      gene, encoding the enzyme dihydroorotate dehydrogenase (DHOD), is potentially a
      case of horizontal gene transfer, as shown by sequencing of this gene from
      additional bacterial and fungal species to generate sufficient data to construct
      a well-supported phylogeny. The DHOD-encoding gene found in S. cerevisiae, URA1
      (YKL216W), appears to have entered the Saccharomycetaceae after the divergence of
      the S. cerevisiae lineage from the Candida albicans lineage and possibly since
      the divergence from the A. gossypii lineage. This gene appears to have come from
      the Lactobacillales, and following its acquisition the endogenous eukaryotic DHOD
      gene was lost. It was also shown that the bacterially derived horizontally
      transferred DHOD is required for anaerobic synthesis of uracil in S. cerevisiae.
      The other gene discussed in detail is BDS1, an aryl- and alkyl-sulfatase gene of
      bacterial origin that we have shown allows utilization of sulfate from several
      organic sources. Among the eukaryotes, this gene is found in S. cerevisiae and
      Saccharomyces bayanus and appears to derive from the alpha-proteobacteria.

PMID- 15947203
TI  - Constitutive signal transduction by mutant Ssy5p and Ptr3p components of the SPS
      amino acid sensor system in Saccharomyces cerevisiae.
AB  - Amino acids in the environment of Saccharomyces cerevisiae can transcriptionally
      activate a third of the amino acid permease genes through a signal that
      originates from the interaction between the extracellular amino acids and an
      integral plasma membrane protein, Ssy1p. Two plasma membrane-associated proteins,
      Ptr3p and Ssy5p, participate in the sensing, which results in cleavage of the
      transcription factors Stp1p and Stp2p, removing 10 kDa of the N terminus of each
      of them. This confers the transcription factors with the ability to gain access
      to the nucleus and activate transcription of amino acid permease genes. To extend
      our understanding of the role of Ptr3p and Ssy5p in this amino acid sensing
      process, we have isolated constitutive gain-of-function mutants in these two
      components by using a genetic screening in which potassium uptake is made
      dependent on amino acid signaling. Mutants which exhibit inducer-independent
      processing of Stp1p and activation of the amino acid permease gene AGP1 were
      obtained. For each component of the SPS complex, constitutive signaling by a
      mutant allele depended on the presence of wild-type alleles of the other two
      components. Despite the signaling in the absence of inducer, the processing of
      Stp1p was more complete in the presence of inducer. Dose response assays showed
      that the median effective concentration for Stp1p processing in the mutant cells
      was decreased; i.e., a lower inducer concentration is needed for signaling in the
      mutant cells. These results suggest that the three sensor components interact
      intimately in a complex rather than in separate reactions and support the notion
      that the three components function as a complex.

PMID- 15947204
TI  - Class I and class II chitin synthases are involved in septum formation in the
      filamentous fungus Aspergillus nidulans.
AB  - The class II and class I chitin synthases of the filamentous fungus Aspergillus
      nidulans are encoded by chsA and chsC, respectively. Previously, we presented
      several lines of evidence suggesting that ChsA and ChsC have overlapping
      functions in maintaining cell wall integrity. In order to determine the functions
      of these chitin synthases, we employed electron and fluorescence microscopy and
      investigated in detail the cell wall of a DeltachsA DeltachsC double mutant
      (DeltaAC mutant) along with the localization of ChsA and ChsC. In the lateral
      cell wall of the DeltaAC mutant, electron-transparent regions were thickened.
      Septa of the DeltaAC mutant were aberrantly thick and had a large pore. Some
      septa were located abnormally close to adjacent septa. A functional hemagglutinin
      (HA)-tagged ChsA (HA-ChsA) and a functional FLAG-tagged ChsC (FLAG-ChsC) were
      each localized to a subset of septation sites. Comparison with the localization
      pattern of actin, which is known to localize at forming septa, suggested that
      ChsA and ChsC transiently exist at the septation sites during and shortly after
      septum formation. Double staining of HA-ChsA and FLAG-ChsC indicated that their
      localizations were not identical but partly overlapped at the septation sites.
      Fluorescence of FLAG-ChsC, but not of HA-ChsA, was also observed at hyphal tips.
      These data indicate that ChsA and ChsC share overlapping roles in septum
      formation.

PMID- 15947205
TI  - Unique mitochondrial genome structure in diplonemids, the sister group of
      kinetoplastids.
AB  - Kinetoplastid flagellates are characterized by uniquely massed mitochondrial DNAs
      (mtDNAs), the kinetoplasts. Kinetoplastids of the trypanosomatid group possess
      two types of mtDNA molecules: maxicircles bearing protein and mitoribosomal genes
      and minicircles specifying guide RNAs, which mediate uridine insertion/deletion
      RNA editing. These circles are interlocked with one another to form dense
      networks. Whether these peculiar mtDNA features are restricted to kinetoplastids
      or prevail throughout Euglenozoa (euglenids, diplonemids, and kinetoplastids) is
      unknown. Here, we describe the mitochondrial genome and the mitochondrial
      ultrastructure of Diplonema papillatum, a member of the diplonemid flagellates,
      the sister group of kinetoplastids. Fluorescence and electron microscopy show a
      single mitochondrion per cell with an ultrastructure atypical for Euglenozoa. In
      addition, DNA is evenly distributed throughout the organelle rather than
      compacted. Molecular and electron microscopy studies distinguish numerous 6- and
      7-kbp-sized mitochondrial chromosomes of monomeric circular topology and relaxed
      conformation in vivo. Remarkably, the cox1 gene (and probably other mitochondrial
      genes) is fragmented, with separate gene pieces encoded on different chromosomes.
      Generation of the contiguous cox1 mRNA requires trans-splicing, the precise
      mechanism of which remains to be determined. Taken together, the mitochondrial
      gene/genome structure of Diplonema is not only different from that of
      kinetoplastids but unique among eukaryotes as a whole.

PMID- 15947207
TI  - Small sense and antisense RNAs derived from a telomeric retroposon family in
      Giardia intestinalis.
AB  - Sequencing of a library of small RNAs from Giardia intestinalis identified a
      novel class of small sense and antisense RNAs homologous to the retroposon family
      GilT/Genie1 that is located at certain telomeres. These small RNAs may contribute
      to silencing GilT expression via the RNA interference pathway.

PMID- 15947206
TI  - Eukaryotic UDP-galactopyranose mutase (GLF gene) in microbial and metazoal
      pathogens.
AB  - Galactofuranose (Gal(f)) is a novel sugar absent in mammals but present in a
      variety of pathogenic microbes, often within glycoconjugates that play critical
      roles in cell surface formation and the infectious cycle. In prokaryotes, Gal(f)
      is synthesized as the nucleotide sugar UDP-Gal(f) by UDP-galactopyranose mutase
      (UGM) (gene GLF). Here we used a combinatorial bioinformatics screen to identify
      a family of candidate eukaryotic GLFs that had previously escaped detection. GLFs
      from three pathogens, two protozoa (Leishmania major and Trypanosoma cruzi) and
      one fungus (Cryptococcus neoformans), had UGM activity when expressed in
      Escherichia coli and assayed in vivo and/or in vitro. Eukaryotic GLFs are closely
      related to each other but distantly related to prokaryotic GLFs, showing limited
      conservation of core residues around the substrate-binding site and flavin
      adenine dinucleotide binding domain. Several eukaryotes not previously
      investigated for Gal(f) synthesis also showed strong GLF homologs with
      conservation of key residues. These included other fungi, the alga Chlamydomonas
      and the algal phleovirus Feldmannia irregularis, parasitic nematodes (Brugia,
      Onchocerca, and Strongyloides) and Caenorhabditis elegans, and the urochordates
      Halocynthia and Cionia. The C. elegans open reading frame was shown to encode UGM
      activity. The GLF phylogenetic distribution suggests that Gal(f) synthesis may
      occur more broadly in eukaryotes than previously supposed. Overall, GLF/Gal(f)
      synthesis in eukaryotes appears to occur with a disjunct distribution and often
      in pathogenic species, similar to what is seen in prokaryotes. Thus, UGM
      inhibition may provide an attractive drug target in those eukaryotes where Gal(f)
      plays critical roles in cellular viability and virulence.

PMID- 15947208
TI  - Apigenin inhibits expression of vascular endothelial growth factor and
      angiogenesis in human lung cancer cells: implication of chemoprevention of lung
      cancer.
AB  - Apigenin is a natural dietary flavonoid. It has recently been shown to have
      anticancer effects on prostate and ovarian cancer cells. However, the molecular
      basis of the effect of apigenin on cancer cells remains to be elucidated. In this
      study, we found that apigenin inhibited A549 lung cancer cell proliferation and
      vascular endothelial growth factor (VEGF) transcriptional activation in a dose
      dependent manner. In an attempt to understand the mechanism of apigenin-inhibited
      VEGF expression, we found that apigenin inhibited VEGF transcriptional activation
      through the hypoxia-inducible factor 1 (HIF-1) binding site and specifically
      decreased HIF-1alpha but not HIF-1beta subunit expression in the cells. In our
      efforts to understand the signaling pathway that mediates VEGF transcriptional
      activation, we found that apigenin inhibited AKT and p70S6K1 activation. When
      testing the effect of apigenin in vivo, we found that apigenin significantly
      inhibited tumor growth in nude mice. Apigenin inhibited HIF-1alpha and VEGF
      expression in the tumor tissues, suggesting an inhibitory effect of apigenin on
      angiogenesis. To confirm this, we showed that apigenin inhibited angiogenesis in
      nude mice using the Matrigel assay. HIF-1alpha and VEGF are well known inducers
      of angiogenesis. Our data suggested that apigenin may inhibit human lung cancer
      angiogenesis by inhibiting HIF-1alpha and VEGF expression, thus providing a novel
      explanation for the anticancer action of apigenin.

PMID- 15947209
TI  - Fiber optic fluorescence microprobe for endodontic diagnosis.
AB  - Successful endodontic therapy requires total debridement as well as complete
      obturation of the root canal to the cemento-dentinal junction. The goal of this
      study was to investigate the feasibility of using quantitative fluorescence
      spectroscopy for the detection and localization of pathological dentin, pulpal
      remnants, and microorganisms within the root canal. Specific aims were to
      identify: 1) characteristic excitation/emission spectra for healthy dentin,
      decayed dentin, enamel, and pulp; 2) the potential of specific spectral data for
      differentiating between these tissues; and 3) the potential of spectral data for
      detecting the presence and identifying four common endodontic pathogens.
      Fluorescence spectra were determined in the tissues of permanent human teeth,
      extirpated healthy and necrotic pulps, and four endodontic pathogens.
      Excitation/emission spectra were collected at 366 nm, 405 nm, and 440 nm
      excitation. Marked differences in spectral signatures between the different
      tissues under investigation were observed. We postulate that the differences in
      fluorescence spectra of decayed vs. healthy dentin are due to the loss of
      mineralized tissue components and increased organic presence and water in these
      tissues. Pulpal tissue showed distinctly different fluorescence spectra from
      healthy and decayed dentin, providing a basis for differentiating between tissue
      categories. Each bacterial species demonstrated distinct spectral emission
      patterns.

PMID- 15947210
TI  - A case study examining classroom instructional practices at a U.S. dental school.
AB  - A case study is used to illustrate how an evaluation strategy was used to assess
      classroom instructional practices following a multiyear institutional curriculum
      revision process. From January through April of 2003, twelve faculty in medicine
      and three faculty in dentistry who taught in the first- and second-year basic
      science courses within the dental curriculum participated in a qualitative study.
      The purpose was to use a formative evaluation process to assess the impact of the
      curriculum revision at the level of classroom instruction. The observations
      revealed that seventeen of the twenty classes observed were teacher-centered,
      passive, and lacked observable effort to help students understand the
      relationship of the lecture content to the oral health problems. Findings
      illustrate the importance of using formative evaluation as a mechanism to assess
      change efforts and how evidence-based study can be used to support initiatives
      directed toward assessing active student learning and problem solving. Raising
      faculty awareness about the importance of acquiring evidence-based educational
      skills, aligning instruction with course goals and objectives, formatively
      assessing teaching, and providing learning experiences that will actually be used
      in practice are essential to ensuring that active learning and critical thinking
      are demonstrated in the curriculum.

PMID- 15947211
TI  - Problem-based learning versus a traditional educational methodology: a comparison
      of preclinical and clinical periodontics performance.
AB  - To evaluate efficacy of a problem-based learning (PBL) pedagogy in preclinical
      and clinical teaching, test scores of 234 undergraduate dental students from the
      conventionally taught classes of 2003 and 2004 were compared with scores of 274
      dental students from the PBL classes of 2005 and 2006. Although the groups' means
      were close together, t-test analysis of scores revealed that PBL students
      performed significantly better than traditional (TRAD) students on midterm
      (p=.0001) and final (p=.015) examinations taken on student partner/mock patients.
      ANOVA comparing the classes with each other showed significant differences for
      the midterm and final, but not for the clinical examination. Further multiple
      comparison tests (Tukey HSD) for the midterm and final revealed that differences
      specifically reflected superior performance of PBL classes against one of the
      TRAD classes (2004). There was no difference in performance between PBL (n=134)
      and TRAD (n=233) students on examinations taken with actual clinical patients who
      were undergoing nonsurgical periodontal treatment. Over a two-year period, PBL
      students rated their program instructors at a mean of 4.41 on a Likert-type scale
      of 1 (not helpful) to 5 (outstanding). The program provides a PBL model for
      teaching preclinical and clinical skills supported by a four-year evaluation of
      manual skills outcomes.

PMID- 15947212
TI  - Validating dental and medical students' evaluations of faculty teaching in an
      integrated, multi-instructor course.
AB  - As more students from various health professions are combined into integrated
      courses, evaluating the teaching quality of individual faculty in these typically
      large, multi-instructor contexts becomes increasingly difficult. Indeed, students
      who lack sufficient recall of a given faculty member or are not committed to the
      evaluation process may respond by marking identical responses to all evaluation
      items (e.g., 3-3-3-3-3), regardless of the specific content of the items on the
      faculty evaluation questionnaire. These "straight-lining" behaviors-more formally
      referred to as monotonic response patterns (MRPs)-often reflect students'
      inattention to the task at hand or lack of motivation to be discriminating, which
      may result in invalid data. This study examines the prevalence of MRP ratings in
      relation to indicators reflective of students' lack of attention to evaluating
      the quality of faculty teaching. Dental and medical students in a required,
      second-year (medicine) basic science course conducted by the medical school and
      taught primarily by medical school faculty completed seven-item faculty
      evaluation forms, along with an anonymous questionnaire measuring their need to
      evaluate, attitudes toward faculty evaluation, and recall of instructors. MRP
      ratings failed to correlate significantly with students' need to evaluate or
      their attitudes toward faculty evaluation. However, among medical students, MRP
      "straight-line" responses were more prevalent for raters who recalled faculty
      members "very well" (p=.04). For dental students, MRPs were associated with less
      accurate recall (p=.01). As such, the validity of faculty evaluations within
      integrated, multi-instructor courses may vary when students rate distinct aspects
      of a teacher's performance identically. In this case-in which medical students'
      greater recall of instructors coincides with MRPs-ratings may suffice as global,
      holistic assessments of an instructor's teaching. For dental students, similar
      ratings may be less viable. Individual item analysis is cautioned under any
      circumstances.

PMID- 15947213
TI  - The ethical climate in academic dentistry in India: faculty and student
      perceptions.
AB  - The aims of this study were to describe both the ethical climate in a private
      dental institution in India and the possible influence of selected factors in
      influencing faculty and students' perception of their institution's ethical
      environment. The Ethical-Climate Questionnaire and the General-Health
      Questionnaire (GHQ-12) were completed by twenty-eight full-time faculty and forty
      seven final-year undergraduate students. Results showed that, overall, the study
      population had a mixed opinion about the ethical climate in their institution.
      Psychological distress and academic experience played an important role in
      shaping the perception of institutional ethics among the study population. The
      results showed that there is a need for better communication of the institution's
      ethical policies and better ethical training to help the faculty and students
      recognize their institution's commitment to ethics.

PMID- 15947214
TI  - An evidence-based journal club for dental residents in a GPR program.
AB  - The journal club offers a significant opportunity to serve as both an educational
      experience but also as a real-world example of the application of the principles
      and practices of evidence-based dentistry (EBD). Designed around the American
      Dental Association's recommended four steps in the implementation of the EBD
      process, the journal clubs are held once per month for GPR residents. The
      structured process allows residents to formulate answerable clinical questions,
      track down with maximum efficiency the best evidence with which to answer the
      questions, critically appraise the evidence for its validity and usefulness, and
      apply the results of this appraisal in clinical practice as appropriate.

PMID- 15947215
TI  - Perceived sources of stress among Greek dental students.
AB  - The goals of this study were to identify sources of stress in dental education
      and to explore the role of year of study and gender on perceived stressors. Five
      hundred and seventy-one undergraduates, officially registered at the University
      of Athens School of Dentistry, participated in the survey by completing a thirty
      item modified version of the Dental Environment Stress Questionnaire. Assigned
      workload, performance pressure, and self-efficacy beliefs constituted the most
      stress-provoking factors. Gender differences were found in most of the perceived
      stressors, whereas stress intensity greatly differed by year of study.
      Multivariate analysis suggested that, irrespective of gender, fourth-year and
      graduating students were less concerned about class work overload, clinical
      training difficulties, and course failing, but were significantly more insecure
      about their professional future. Entry-level students appeared to be the most
      concerned about the lack of time for relaxation. However, they were the least
      stressed about completing graduation requirements compared with the rest of their
      peers. Possible strategies for reducing stress in Greek dental education are
      considered in the light of these findings.

PMID- 15947216
TI  - Compliance with infection control programs in private dental clinics in Jordan.
AB  - The aim of this study was to assess the compliance of general dental
      practitioners (GDPs) in the private sector in North Jordan with infection control
      measures. A pilot-tested questionnaire about infection control measures was
      distributed in March 2004 to 120 private practices. The response rate was 91.66
      percent. About 77 percent of dentists usually ask their patients about medical
      history, 36 percent were vaccinated against hepatitis B, 81.8 percent wear and
      change gloves during treatment and between patients, and 54.5 percent wear and
      change masks during treatment and between patients. Most dental practitioners
      (95.4 percent) reported that they changed extraction instruments and burs between
      patients. All dental practitioners reported that they changed saliva ejectors
      between patients, but only 41.8 percent changed handpieces between patients.
      Approximately 63 percent (69/110) used autoclaves for sterilization, 47.3 percent
      (52/110) used plastic bags to wrap sterilized instruments, and only 18 percent
      (20/110) disinfected impressions before sending them to dental labs. Fourteen
      percent used rubber dams in their clinics, and only 31.8 percent had special
      containers for sharps disposal. Based on these responses, approximately 14
      percent of general dentists in this sample were considered to be compliant with
      an inventory of recommended infection control measures. In Jordan, there is a
      great need to provide formal and obligatory infection control courses and
      guidelines for private dentists by the Ministry of Health and the dental
      association in addition to distribution of standard infection control manuals
      that incorporate current infection control recommendations.

PMID- 15947217
TI  - Predictors of schizophrenia--a review.
AB  - Schizophrenia is an aetiologically heterogeneous syndrome that usually becomes
      overtly manifest in adolescence and early adulthood, but in many cases subtle
      impairments in neurointegrative function are present from birth; hence it is
      considered to be a disorder with a neurodevelopmental component. The strongest
      risk factor that has been identified is familial risk with genetic loading. Other
      risk factors include pregnancy and delivery complications, infections during
      pregnancy, disturbances of early neuromotor and cognitive development and heavy
      cannabis use in adolescence. Unfortunately, to date it has not been possible to
      utilize the predictors of the disorder that have been identified in primary
      preventative interventions in a general population. However, some authors have
      claimed that in future it might be possible to reduce the risk for developing
      schizophrenia through general health policy. In clinical settings, it is helpful
      to map out possible early risk factors, at least familial risk for psychosis,
      especially in child, adolescent and young adult mental patients. Furthermore, in
      the future we may have predictive models combining data from genetic factors for
      schizophrenia, antenatal risk factors, childhood and adolescent development and
      clinical symptomatology, as well as brain structural and functional
      abnormalities.

PMID- 15947218
TI  - An approach to maintain orthodontic alignment of lower incisors without the use
      of retainers.
AB  - The purpose of this investigation was to examine the long-term stability of
      orthodontic alignment of lower incisors without the use of retainers. The study
      sample comprised 56 patients treated according to a protocol that included over
      correction of rotated teeth at an early stage of treatment and systematic enamel
      reduction (stripping) of the approximal surfaces in the mandibular anterior
      region, both during treatment and follow-up. Care was also taken to maintain
      dental arch form and to avoid lateral expansion of the lower dental arch and
      proclination of the incisors. Dental study casts were obtained pre-treatment, at
      the end of treatment, and 3 years post-treatment. Alignment of the mandibular
      incisors was recorded using Little's irregularity index. The inter-canine
      distance and the sum of the mesio-distal widths of the mandibular incisors and
      canines were also measured. The total amount of enamel removed from the
      approximal surfaces of the lower anterior teeth ranged from 0.3 to 5.0 mm (mean
      1.9 mm). The mean increase in irregularity index score of 0.6 from post-treatment
      to 3 years follow-up indicated good stability. In 45 per cent of the patients the
      change in score during this period was less than 0.5, indicating that the
      treatment approach presented may be considered an alternative strategy to
      placement of lower retainers to safeguard the stability of alignment of
      mandibular incisors.

PMID- 15947219
TI  - Orthodontically induced root and alveolar bone resorption: inhibitory effect of
      systemic doxycycline administration in rats.
AB  - The aim of the present study was to investigate the effect of systemic
      administration of low-dose doxycycline (DC) on orthodontic root resorption. The
      effect on alveolar bone, the cell population involved, and the amount of tooth
      movement were also evaluated.Fifty-six 40-50-day-old male Wistar rats were used.
      Six animals served as untreated controls. Six animals were only administered DC
      for 7 days, by means of a mini-osmotic pump implanted subcutaneously. In 44
      animals the maxillary first molar was mesialized by a fixed orthodontic appliance
      exerting 50 g force upon insertion. In 28 of these animals DC was administered at
      the time of appliance insertion and throughout the experiment. The animals were
      sacrificed 7, 10 or 14 days after force application and block sections processed
      for analysis. An area including the mesial aspect of the distopalatal root and
      the adjacent inter-radicular alveolar bone was histomorphometrically evaluated.
      The root resorption area, absolute alveolar bone area, distance between first and
      second molars, number of odontoclasts, osteoclasts, mononuclear cells on the
      root, tartrate-resistant acid phosphatase (TRAP)-positive cells on the root,
      bone, and in the periodontal ligament (PDL) were compared between DC-treated and
      non-DC-treated animals. The results revealed a significant reduction in root
      resorption, the number of odontoclasts, osteoclasts, mononuclear cells on the
      root surface, and TRAP-positive cells on the root and bone for the DC
      administered group. The absolute alveolar bone area was greater, whereas the
      distance between the first and second molars did not differ between groups. In
      conclusion, systemic administration of low-dose DC in rats may have an inhibitory
      effect on orthodontically induced resorptive activity.

PMID- 15947220
TI  - An innovative adhesive procedure for connecting transpalatal arches with palatal
      implants.
AB  - The aim of this presentation is to describe an innovative adhesive procedure for
      connecting palatal implants with transpalatal arches (TPAs). The steps required
      for completing the procedure, the costs involved and the requisite time were
      reviewed and compared with those of two alternative procedures reported in the
      literature. To establish the stability and reliability of the procedure in vitro,
      tensile stress tests were performed. The results were evaluated in view of a
      potential loss of anchorage and compared with reported data. The innovative
      adhesive procedure ensured a stable and precise connection between TPAs and
      palatal implants during a single visit in a chair-side time of 42 minutes. The
      costs incurred were euro 12.33. The composite-connected component parts resisted
      breakage up to a mean force of 3323.16 cN. Absolute stability of the TPA-palatal
      implant connection in terms of maximal anchorage was limited to a mean force of
      408.05 cN at a wire strength of 0.036 inches.

PMID- 15947221
TI  - Office reconditioning of stainless steel orthodontic attachments.
AB  - An investigation was conducted to determine a simple, effective method for
      reconditioning stainless steel orthodontic attachments in the orthodontic office.
      In total, 100 new brackets were bonded to premolar teeth, then debonded and the
      bond strength recorded as a control for the reconditioning process. The debonded
      brackets were divided into six groups and each group reconditioned using
      different techniques as follows: attachments in four groups were flamed and then
      either (1) sandblasted, (2) ultrasonically cleaned, (3) ultrasonically cleaned
      followed by silane treatment, (4) rebonded without further treatment. Of the two
      remaining groups, one was sandblasted, while the brackets in the other were
      roughened with a greenstone. The brackets were rebonded to the premolar teeth
      after the enamel surfaces had been re-prepared, and their bond strengths
      measured. The results indicated that sandblasting was the most effective in
      removing composite without a significant change in bond strength compared with
      new attachments. Silane application did not improve the bond strength values of
      flamed and ultrasonically cleaned brackets. Attachments that had only been flamed
      had the lowest bond strength, followed by those that had been roughened with a
      greenstone.

PMID- 15947222
TI  - A stainless steel bracket for orthodontic application.
AB  - Aesthetics has become an essential element when choosing orthodontic fixed
      appliances. Most metallic brackets used in orthodontic therapy are made from
      stainless steel (SS) with the appropriate physical properties and good corrosion
      resistance, and are available as types 304, 316 and 17-4 PH SS. However,
      localized corrosion of these materials can frequently occur in the oral
      environment. This study was undertaken to evaluate the accuracy of sizing,
      microstructure, hardness, corrosion resistance, frictional resistance and
      cytotoxicity of commercially available Mini-diamond (S17400), Archist (S30403)
      and experimentally manufactured SR-50A (S32050) brackets. The size accuracy of
      Mini-diamond was the highest at all locations except for the external horizontal
      width of the tie wing (P < 0.05). Micrographs of the Mini-diamond and Archist
      showed precipitates in the grains and around their boundaries. SR-50A showed the
      only austenitic phase and the highest polarization resistance of the tested
      samples. SR-50A also had the highest corrosion resistance [SR-50A, Mini-diamond
      and Archist were 0.9 x 10(-3), 3.7 x 10(-3), and 7.4 x 10(-3) mm per year (mpy),
      respectively], in the artificial saliva. The frictional force of SR-50A decreased
      over time, but that of Mini-diamond and Archist increased. Therefore, SR-50A is
      believed to have better frictional properties to orthodontic wire than Mini
      diamond and Archist. Cytotoxic results showed that the response index of SR-50A
      was 0/1 (mild), Mini-diamond 1/1 (mild+), and Archist 1/2 (mild+). SR-50A showed
      greater biocompatibility than either Mini-diamond or Archist. It is concluded
      that the SR-50A bracket has good frictional property, corrosion resistance and
      biocompatibility with a lower probability of allergic reaction, compared with
      conventionally used SS brackets.

PMID- 15947223
TI  - An investigation into the use of two polyacid-modified composite resins
      (compomers) and a resin-modified glass poly(alkenoate) cement used to retain
      orthodontic bands.
AB  - The aim of this investigation was to determine the effectiveness of a
      conventional glass poly(alkenoate) cement (Intact) and newer polyacid-modified
      composite resin cements (Transbond Plus and Ultra Band-Lok) to retain orthodontic
      bands. In the in vitro part of this study, stainless steel bands were cemented to
      240 extracted third molar teeth in three test groups comprising Intact, Transbond
      Plus and Ultra Band-Lok. The force to deband (N) for all three cements was
      recorded using an Instron universal testing machine after the following
      observation periods: 20 minutes and 3, 6 and 12 months. The results indicated
      that all three cements increased their median force to deband after 12 months. Of
      the two compomers, Transbondtrade mark Plus demonstrated the highest median force
      to deband at all four time intervals. In the in vivo part of the study, 30
      patients participated in a randomized cross-mouth clinical trial where the molar
      bands were cemented in place using either Intact or Transbond Plus. Ultra Band
      Lok was not used in the clinical part of the study. The results showed there to
      be no clinically significant difference in band failure rates between the two
      cements. When patients were asked to score each for taste, there was a
      significant difference, with the glass poly(alkenoate) cement (Intact) being more
      acceptable than the polyacid-modified composite Transbond Plus (P < 0.001). No
      significant differences were observed in the in vitro median force to deband or
      in vivo band failure rates between the glass poly(alkenoate) cement and the
      polyacid-modified composite resins. The choice of cementing agent can therefore
      be made on patient factors, e.g. taste, or operator factors, e.g. ease of
      handling, cost and shelf life.

PMID- 15947224
TI  - A jig for measuring incisor inclination.
AB  - The aim of this study was to design and construct a jig for measuring the
      inclination of the upper incisors to the maxillary plane and of the lower
      incisors to the mandibular plane. After several prototypes had been tested, the
      required properties for a successful jig were identified and a simple inexpensive
      device was produced. Measurements obtained when using the jig on 51 subjects were
      compared with cephalometric values by means of regression analysis. This revealed
      that measurements obtained using the jig against the upper and then the lower
      incisor crowns could be converted to cephalometric incisor angulations with 96
      per cent accuracy to 10 degrees, by adding 23 and 3 degrees, respectively. The
      jig was accurate to 5 degrees on 69 per cent of occasions for the upper teeth.
      The 5 degrees accuracy with the lower incisors was only 27 per cent, although
      over a 6 degree range it improved to 78 per cent. For upper and lower tooth
      measurements combined, the jig was accurate to within 6 degrees on 75 per cent of
      occasions.

PMID- 15947225
TI  - Anterior tooth morphology and its effect on torque.
AB  - This study was undertaken to determine the variation in crown-root angle (CRA) of
      the upper incisors and canines as well as the variation in their labial contour.
      In addition, the influence of the variability of the labial contour and of
      different bracket heights on torque was evaluated. Proximal radiographs were
      taken of 160 extracted maxillary teeth (81 incisors and 79 canines). They were
      digitized and analysed with Jasc Paint Shop Pro 7TM and Mathcad 2001
      Professional. The incisal edge, the centre of the cemento-enamel junction (CEJ),
      and the root apex were digitized to define the crown and root long axis. For all
      teeth the CRA was measured. At several heights of the labial surface a tangent
      was determined, enabling measurement of the inclination of the labial surface.
      The CRA had great variability, ranging from 167 to 195 degrees for the canines
      (mean value 183 degrees) and from 171 to 195 degrees for the incisors (average
      184 degrees). The mean inclinations of the labial surfaces for the incisors
      varied greatly. Between 4 and 4.5 mm from the incisal edge the standard
      deviations (SD) were the smallest and between 2 and 4.5 mm from the incisal edge
      the labial surface angle differed by approximately 10 degrees. For the canines
      the mean inclinations of the buccal surface also varied. This angle differed by
      around 10 degrees between 2 and 4.5 mm from the incisal edge, but the SD were
      much larger than for the incisors. It can be concluded that placement of a
      bracket on a tooth at varying heights, still within a clinically acceptable
      range, results in important differences in the amount of root torque.

PMID- 15947226
TI  - The role of psycho-social factors in headgear compliance.
AB  - The aim of this study was to identify the role of psycho-social factors in
      headgear compliance. Fifty-one patients, with an Angle Class II division 1
      malocclusion comprised the study sample. The treatment plan aimed to correct the
      malocclusion using cervical pull headgear. An electronic module timer was
      attached to the neckstrap to evaluate the number of hours the patients wore the
      headgear. One of their parents was asked to answer the Child Behaviour Checklist
      (CBCL), which defines a patient's behaviour. The patients were monitored for 6
      months and the modules were measured at the end of each 2 month period. Mann
      Whitney U and Chi square tests were used to analyse the data. The patients were
      separated into groups according to their compliance. The results showed that
      although there were significant differences in the use of headgear between the
      groups (P < or = 0.001), age, gender, and CBCL subgroup scores were not
      statistically significant (P > 0.05).

PMID- 15947227
TI  - Change in cranio-cervical angulation following orthognathic surgery.
AB  - Changes in natural head posture (NHP) were investigated in 33 patients (10 males,
      23 females) with an age range of 16-40 years (median 21 years) following
      orthognathic surgery to change vertical face height. The reproducibility of the
      radiographer's technique of taking radiographs in NHP was investigated using a
      photographic method and found to be acceptable. The patients were divided into
      two groups: group 1, patients who had more than 3 mm of vertical change in
      anterior total face height (ATFH) and group 2, those who had less than 3 mm
      vertical change. For group 1 there was a significant relationship between ATFH
      change and cranio-cervical angulation (NSL/OPT) change (r = 0.532, P = 0.023),
      compared with group 2 (r = -0.247, P = 0.376). A similar relationship was
      revealed between lower anterior face height (LAFH)/ATFH ratio and NSL/OPT, where
      the correlation was also higher in group 1 (r = -0.635, P = 0.005) compared with
      group 2 (r = -0.182, P = 0.515). The correlation between cranio-vertical
      angulation (NSL/VER) and ATFH was not significant for group 1 (r = 0.406) or
      group 2 (r = 0.239) patients. Additionally, NSL/VER and LAFH/ATFH correlation for
      the two groups was not significant (r = -0.392 and -0.338, respectively). There
      appears to be a relationship between the reduction in vertical face height
      following orthognathic surgery and neck posture (as indicated by NSL/OPT). As no
      significant relationship was found between the reduction in face height and head
      posture (as indicated by NSL/VER) this suggests that neck posture, rather than
      head posture, had changed.

PMID- 15947228
TI  - The psychosocial effects of cleft lip and palate: a systematic review.
AB  - This systematic review examined the published scientific research on the
      psychosocial impact of cleft lip and palate (CLP) among children and adults. The
      primary objective of the review was to determine whether having CLP places an
      individual at greater risk of psychosocial problems. Studies that examined the
      psychosocial functioning of children and adults with repaired non-syndromal CLP
      were suitable for inclusion. The following sources were searched: Medline
      (January 1966-December 2003), CINAHL (January 1982-December 2003), Web of Science
      (January 1981-December 2003), PsycINFO (January 1887-December 2003), the
      reference section of relevant articles, and hand searches of relevant journals.
      There were 652 abstracts initially identified through database and other
      searches. On closer examination of these, only 117 appeared to meet the inclusion
      criteria. The full text of these papers was examined, with only 64 articles
      finally identified as suitable for inclusion in the review. Thirty of the 64
      studies included a control group. The studies were longitudinal, cross-sectional,
      or retrospective in nature.Overall, the majority of children and adults with CLP
      do not appear to experience major psychosocial problems, although some specific
      problems may arise. For example, difficulties have been reported in relation to
      behavioural problems, satisfaction with facial appearance, depression, and
      anxiety. A few differences between cleft types have been found in relation to
      self-concept, satisfaction with facial appearance, depression, attachment,
      learning problems, and interpersonal relationships. With a few exceptions, the
      age of the individual with CLP does not appear to influence the occurrence or
      severity of psychosocial problems. However, the studies lack the uniformity and
      consistency required to adequately summarize the psychosocial problems resulting
      from CLP.

PMID- 15947229
TI  - An update on the analysis of agreement for orthodontic indices.
AB  - The training of clinicians in the correct use of commonly used orthodontic
      indices involves calibration. The level of agreement between the trainee and a
      standard is assessed both as a measure of reproducibility and the success of
      training programmes. For the Peer Assessment Rating (PAR) index and the Index of
      Complexity, Outcome and Need (ICON), the recommended level of acceptable inter
      rater agreement is no more than +/-12 and +/-18, respectively. Many commonly used
      methods of analysing this type of agreement are inappropriate. The method used in
      this investigation allows the calculation of limits of agreement, which easily
      demonstrate any major departures in agreement between trainee scores and standard
      scores. The basic method assumes that the differences between trainee and
      standard scores are normally distributed and that there is no relationship
      between these differences and the magnitude of the index. An extension to this
      approach is required when the assumptions of the basic method are not upheld.
      This extension provides a regression-based approach to calculating limits of
      agreement. The results of this study demonstrate that the assumptions of the
      basic approach need to be checked for each comparison of trainee versus standard.
      In addition, regression-based methods are a more accurate means of calculating
      limits of agreement when these assumptions are not upheld. They also provide more
      information about bias and the range of disagreement between raters.

PMID- 15947230
TI  - Self-perception of malocclusion among north Jordanian school children.
AB  - This study was undertaken to assess the factors affecting self-perception and the
      demand for orthodontic treatment among north Jordanian school children. In total,
      1404 students randomly selected to represent five geographical areas of northern
      Jordan were examined. The students were further subgrouped according to gender
      (858 females, 546 males), age (985 13 year olds, 419 17 year olds) and
      rural/urban place of residence (212 rural, 1192 urban). The aesthetic component
      (AC) of the Index of Orthodontic Treatment Need (IOTN) was used as an assessment
      measure of the need for orthodontic treatment. The self-perception of
      malocclusion was evaluated by asking each student to identify which photograph on
      the AC scale most closely matched the appearance of their anterior teeth. The
      demand for orthodontic treatment was measured by asking the students: "Do you
      feel it is necessary to have your teeth straightened by an orthodontist?"
      Differences between the self-perception of malocclusion among the different
      groups were tested using the chi-squared test.The results showed that the
      majority of students rated their dentition from grades 1 to 4, with a tendency
      for the females and older school children to score their teeth as more attractive
      than males and younger children (P < 0.05, P < 0.001, respectively). Rural and
      urban school children did not differ in the perception of their own dentition.
      The self-perception scores of subjects within the no aesthetic need, borderline
      need and definite need groups differed significantly (P < 0.001). The subjects
      who reported a definite need perceived their teeth to be worse than the other two
      groups. The demand for orthodontic treatment was found to be affected by gender
      (P < 0.01) and rural/urban areas of living (P < 0.05).

PMID- 15947231
TI  - Towards a comprehensive model for the study of compliance in orthodontics.
AB  - The aims of the present study were to explore methods used by Dutch orthodontists
      in daily practice to estimate and stimulate patient compliance, and to develop a
      theoretical model of compliance. A questionnaire, containing 38 items, was
      distributed among participants at the annual congress of the Dutch Society of
      Orthodontists in September 2002. The items concerned the need for and the level
      of patient adherence during orthodontic treatment, modes of estimating and
      stimulating compliance, and perceived reasons for non-compliance. Based on this
      pilot study and on an extensive literature search, a model for future research
      was developed in which concepts related to compliance in orthodontics were
      systematically organized. Of the 88 orthodontists who attended the congress, 51
      responded (mean age 47 years, 22 per cent females). The respondents considered
      compliance to be of vital importance for a successful treatment result. Most
      patients were regarded as moderate compliers. The respondents believed that a
      lack of awareness of dental problems, a lack of motivation to co-operate, and
      personal problems were the main reasons for non-compliance. Only indirect methods
      were used to estimate compliance. It was concluded that Dutch orthodontists used
      subjective methods to measure compliance in daily practice, and that a
      theoretical model was needed to be able to examine compliance in orthodontics in
      a more systematic way. A multiple assessment of compliance, using a variety of
      research methods, seems to be the most appropriate way at present to ensure
      accuracy in measuring levels of patient compliance in orthodontics.

PMID- 15947232
TI  - Archwire seating forces produced by different ligation methods and their effect
      on frictional resistance.
AB  - The aims of this study were to determine the mean tensile force of four different
      elastomeric modules, the archwire seating force of different ligation methods,
      and its effect on frictional resistance. To determine the mean tensile force,
      each elastomeric module (purple, grey, Alastik, and SuperSlick) was extended by 5
      mm using two hooks attached to a load cell using a Nene M3000 testing machine. To
      assess the median archwire seating force, a maxillary premolar bracket (3M
      Unitek) was welded to a sheet of stainless steel (SS) and glued to a Perspex
      block. The bracket base was removed and the cut continued into the Perspex below.
      A length of test wire was taken and bent to form a "U" shape, with the middle
      portion 20 mm in length. The free ends of the wire were secured to the load cell
      of the Nene testing machine. Two wire sizes were tested, 0.017 x 0.025 and 0.019
      x 0.025 inch SS. The load cell was activated and the force with which the wire
      was displaced into the slot by the ligation method was measured. Four types of
      elastomeric module were tested together with a pre-formed 0.09 inch SS ligature.
      The experimental method used to determine the mean frictional force of each
      module and wire size was carried out using a method described previously.
      Statistically significant differences existed in the mean tensile forces and
      median archwire seating forces between the elastomeric modules. Grey modules with
      either size wire produced the lowest median archwire seating force, whereas SS
      ligatures produced the highest forces. SS ligatures with either wire produced the
      lowest mean frictional forces, whereas grey modules produced significantly higher
      mean frictional force (P < 0.01). The force with which the wire was seated into
      the bracket did not seem to be related to the subsequent amount of mean
      frictional force produced.

PMID- 15947233
TI  - Dental age in Dutch children.
AB  - Dental age was studied in a sample of 451 Dutch children (226 boys and 225 girls)
      according to the method of Demirjian. They were born between 1972 and 1993 and
      were between 3 and 17 years of age at the time a dental pantomogram (DPT) was
      obtained. All children were placed in the age group closest to their
      chronological age. All 451 DPTs were scored by one examiner. A subset of 52 DPTs
      was scored by a second examiner and the intra-class correlation coefficient (ICC)
      and Cohen's kappa were calculated. The ICC was 0.99 and Cohen's kappa 0.68. Boys
      and girls were analysed separately.A significant difference was found between
      chronological age and dental age. On average, the Dutch boys were 0.4 years and
      the girls 0.6 years ahead of the French-Canadian children analysed by Demirjian.
      Therefore, the French-Canadian standards were not considered suitable for Dutch
      children. New graphs for the Dutch population were constructed using a logistic
      curve with the equation Y = 100*{1/(1 + e(-alpha(x - x0)))} as a basis. The 90
      per cent confidence interval was calculated. To determine whether the logistic
      curve was correct, a residual analysis was carried out and scatter plots of the
      differences were made. The explained variance was 93.9 per cent for the boys and
      94.8 per cent for the girls. Both the residual analysis and the scatter plots
      indicated that the logistic curve was appropriate for use with Dutch children. In
      addition to the graphs, tables were produced which transfer the maturity scores
      calculated by the method of Demirjian into Dutch dental age.

PMID- 15947234
TI  - The effect of head rotation on cephalometric radiographs.
AB  - The aim of this study was to identify the potential projection errors of lateral,
      postero-anterior (PA) and submentovertex (SMV) cephalometric radiographs due to
      head rotation in the vertical z-axis. For this investigation, a complete human
      dry skull of an adult was used. The skull was rotated from 0 to +/-14 degrees at
      2 degree intervals. A vertical axis, the z-axis, was used as the rotational axis
      to expose 15 lateral and 15 PA cephalometric radiographs. The skull was tilted on
      each side, again at 2 degree intervals, to expose the 15 SMV films. A series of
      linear and angular measurements was carried out on all cephalograms. The results
      revealed that horizontal linear and angular measurements between the horizontal
      planes on lateral cephalograms were subject to changes from 16.1 to 44.7 per cent
      with a 14 degree rotation of the head position. For PA cephalograms, again
      horizontal linear measurements, particularly mandibular length, were subject to a
      projection error of up to 34.9 per cent with head rotation. On the other hand,
      projection errors were within the 3-4 per cent limit for SMV radiography. The
      findings indicate that: (1) linear measurements and the measurement of angles
      between the horizontal planes are likely to be affected by head rotation in
      lateral cephalograms, (2) angular measurements demonstrate smaller variations
      with changing rotation of the head in PA cephalograms, (3) SMV radiographs are
      less vulnerable to head rotation. Vertical linear measurements of lateral
      cephalograms and angular measurements of PA radiographs are more reliable in
      minimizing the projection errors associated with head rotation.

PMID- 15947235
TI  - Supreme Court strikes ban on private health insurance.

PMID- 15947236
TI  - Regulation of tissue factor--mediated initiation of the coagulation cascade by
      cell surface grp78.
AB  - OBJECTIVE: To test the hypothesis that Grp78 negatively regulates cell surface
      tissue factor (TF) procoagulant activity and whether this is mediated by physical
      interaction. METHODS AND RESULTS: Biopanning with phage-displayed peptidyl
      libraries has identified peptide probes that bind selectively in vivo to the
      surface of atherosclerotic plaque endothelium. The highest affinity peptide,
      EKO130, binds 78-kDa glucose regulated protein (Grp78). Grp78 participates in
      numerous pathological processes, including the regulation of the coagulation
      cascade, but the mechanism of Grp78 regulation of coagulation is unknown. To
      characterize this function, we analyzed the effect of Grp78 on TF-mediated
      procoagulant activity on murine brain endothelial cells (bEND.3) and macrophage
      like (RAW) cells, which are relevant in mediation of atherothrombosis. We show
      that Grp78 is present on the surface of endothelium and monocyte/macrophage-like
      cells in atherosclerotic lesions. Inhibition of Grp78 resulted in increased
      procoagulant activity. We demonstrate that Grp78 negatively regulates
      procoagulant activity by interacting physically with the TF extracellular domain
      on the cell surface. CONCLUSIONS: The evidence indicates that Grp78 negatively
      regulates TF functional activity via direct binding to and functional inhibition
      of TF. Identification of the mechanism by which Grp78 regulates TF function may
      advance insight into the pathobiology of atherosclerosis and associated arterial
      thrombosis.

PMID- 15947237
TI  - Coronary artery calcium outperforms carotid artery intima-media thickness as a
      noninvasive index of prevalent coronary artery stenosis.
AB  - OBJECTIVE: Increased carotid artery intima-media thickness (IMT) and increased
      coronary artery calcium (CAC) are noninvasive surrogate indices of prevalent
      coronary artery disease (CAD). We compared CAC to IMT for noninvasive detection
      of prevalent CAD in participants whose coronary status was identified by coronary
      angiography. METHODS AND RESULTS: Male and female CAD patients (> or =50%
      stenosis in one or more coronary artery, n=79) and controls (no lumen
      irregularities, n=93) were identified using coronary angiography. Mean maximum
      carotid IMT was quantified using B-mode ultrasound and total CAC was measured
      using ECG-gated helical computed tomography (HCT). Carotid IMT was approximately
      20% higher in CAD cases compared with controls (P<0.001), whereas mean CAC was
      1000% higher in CAD cases than controls (P<0.0001). In multivariable models
      adjusted for age and sex, IMT greater than the median (1.13 mm) was associated
      with 2-fold increase in likelihood of prevalent CAD compared with scores below
      that cut point (P=0.015). CAC scores that exceeded the median score of 92 were
      associated with 28-fold increase in likelihood of prevalent CAD (P<0.0001).
      Although associations of increased IMT with prevalent CAD were similar in males
      and females, CAC scores above the median in females were associated with 39-fold
      increase in odds of prevalent CAD, whereas males with elevated CAC had 19-fold
      risk of CAD. CONCLUSIONS: HCT-measured CAC compares favorably with carotid IMT
      measured by B-mode ultrasound as a noninvasive index of prevalent CAD.

PMID- 15947238
TI  - Conditional knockout of macrophage PPARgamma increases atherosclerosis in C57BL/6
      and low-density lipoprotein receptor-deficient mice.
AB  - OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is highly
      expressed in macrophage-derived foam cells of atherosclerotic lesions, and its
      expression may have a dramatic impact on atherosclerosis. METHODS AND RESULTS: To
      investigate the contribution of macrophage PPARgamma expression on atherogenesis
      in vivo, we generated macrophage-specific PPARgamma knockout (MacPPARgammaKO)
      mice. C57BL/6 and low-density lipoprotein (LDL) receptor-deficient (LDLR(-/-))
      mice were reconstituted with MacPPARgammaKO or wild-type marrow and challenged
      with an atherogenic diet. No differences were found in serum lipids between
      recipients reconstituted with MacPPARgammaKO and wild-type marrow. In contrast,
      both C57BL/6 and LDLR(-/-) mice transplanted with MacPPARgammaKO marrow had
      significantly larger atherosclerotic lesions than control recipients. In
      addition, MacPPARgammaKO-->LDLR(-/-) mice had higher numbers of macrophages in
      atherosclerotic lesions compared with controls. Peritoneal macrophages isolated
      from the MacPPARgammaKO mice had decreased uptake of oxidized but not acetylated
      LDL and showed no changes in either cholesterol efflux or inflammatory cytokine
      expression. Macrophages from MacPPARgammaKO mice had increased levels of
      migration and CC chemokine receptor 2 (CCR2) expression compared with wild-type
      macrophages. CONCLUSIONS: Thus, macrophage PPARgamma deficiency increases
      atherosclerosis under conditions of mild and severe hypercholesterolemia,
      indicating an antiatherogenic role for PPARgamma, which may be caused, at least
      in part, by modulation of CCR2 expression and monocyte recruitment.

PMID- 15947240
TI  - Are remnant-like particles independent predictors of coronary heart disease
      incidence? The Honolulu Heart study.
AB  - BACKGROUND: Remnant-like particles have been proposed as a new risk factor for
      coronary heart disease (CHD). This is the first long-term prospective
      investigation of the relationship between remnant-like particles and a
      cardiovascular disease outcome in healthy men. METHODS AND RESULTS: A cohort of
      1156 Japanese-American men aged 60 to 82 from the Honolulu Heart Program was
      followed for 17 years. During that period 164 incident cases of CHD were
      identified. In multivariate Cox regression analyses, baseline remnant-like
      particle cholesterol (RLP-C) and triglyceride (RLP-TG) levels were significantly
      related to CHD incidence independently of nonlipid cardiovascular risk factors
      and of total cholesterol or high-density and low-density lipoprotein cholesterol
      levels. Total triglyceride levels were an independent predictor of CHD incidence.
      However, in models including RLP and triglyceride level simultaneously, neither
      variable was significant when adjusted for the other. This finding can be
      attributed to the strong correlation between RLP-C and RLP-TG levels and total
      triglycerides. When individuals with normal triglyceride levels (n=894) were
      separated from those with elevated triglycerides (n=260), the association between
      RLPs and CHD relative risk was only significant for the group with elevated
      triglyceride levels. CONCLUSIONS: RLP levels predicted CHD incidence
      independently of nonlipid risk factors and of total cholesterol or high-density
      and low-density lipoprotein cholesterol levels. However, RLP levels did not
      provide additional information about CHD incidence over and above total
      triglyceride levels. Therefore, this study does not support the need for testing
      of remnants in men if measures of fasting triglycerides are available.

PMID- 15947239
TI  - Mineral volume and morphology in carotid plaque specimens using high-resolution
      MRI and CT.
AB  - OBJECTIVE: High-resolution MRI methods have been used to evaluate carotid artery
      atherosclerotic plaque content. The purpose of this study was to assess the
      performance of high-resolution MRI in evaluation of the quantity and pattern of
      mineral deposition in carotid endarterectomy (CEA) specimens, with quantitative
      micro-CT as the gold standard. METHODS AND RESULTS: High-resolution MRI and CT
      were compared in 20 CEA specimens. Linear regression comparing mineral volumes
      generated from CT (VCT) and MRI (VMRI) data demonstrated good correlation using
      simple thresholding (VMRI=-0.01+0.98VCT; R2=0.90; threshold=4xnoise) and k-means
      clustering methods (VMRI=-0.005+1.38VCT; R2=0.93). Bone mineral density (BMD) and
      bone mineral content (BMC [mineral mass]) were calculated for CT data and BMC
      verified with ash weight. Patterns of mineralization like particles, granules,
      and sheets were more clearly depicted on CT. CONCLUSIONS: Mineral volumes
      generated from MRI or CT data were highly correlated. CT provided a more detailed
      depiction of mineralization patterns and provided BMD and BMC in addition to
      mineral volume. The extent of mineralization as well as the morphology may
      ultimately be useful in assessing plaque stability.

PMID- 15947241
TI  - Association of the -92C/G and 807C/T polymorphisms of the alpha2 subunit gene
      with human platelets alpha2beta1 receptor density.
AB  - OBJECTIVE: Platelet adhesion to the subendothelial tissue via the collagen
      receptor alpha2beta1 is a crucial event in vascular biology. Although evidence
      has been provided that the number of platelets alpha2beta1 copies is genetically
      determined, the molecular change primary responsible has not been yet elucidated.
      The aim of our present study was to investigate the effect of combined
      polymorphisms within both regulatory (-52C/T and -92C/G) and coding regions
      (807C/T and 1648A/G) of the alpha2 subunit gene on human platelets alpha2beta1
      receptor density and/or susceptibility to coronary artery disease (CAD). METHODS
      AND RESULTS: Among 254 cardiac surgery patients, no evidence was found for an
      association between the alpha2 subunit gene polymorphisms and CAD. In contrast,
      in a subgroup of 113 patients, we observed a significant association between all
      polymorphisms except -52C/T and alpha2beta1 receptor level. Furthermore, when 3
      groups of patients were defined according to the tertiles of platelets
      alpha2beta1 copies, the -92C/807T haplotype was more frequent in the group of
      patients with high alpha2beta1 receptor level. CONCLUSIONS: These results suggest
      that an individual effect of each polymorphism located either in the coding or
      promoter sequence of the alpha2 gene may act in combination to modulate
      variations in platelets alpha2beta1 receptor density.

PMID- 15947242
TI  - Complex trait locus linkage mapping in atherosclerosis: time to take a step back
      before moving forward?

PMID- 15947243
TI  - Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E
      deficient mice.
AB  - OBJECTIVE: The direct role of leptin in vascular disease remains controversial.
      The objective of this study was to examine the effects of leptin treatment on
      atherosclerosis and thrombosis in atherosclerotic-prone mice. METHODS AND
      RESULTS: Sixteen-week-old, male apolipoprotein E-deficient mice were treated with
      injections of recombinant leptin (125 microg per day IP; n=10) or vehicle (n=10)
      for 4 weeks. Leptin treatment resulted in reduced epididymal fat (352+/-30.7
      versus 621+/-61.5 mg; P=0.005) and fasting insulin (0.57+/-0.25 versus 1.7+/-0.22
      ng/mL; P=0.014). Despite these metabolic benefits, leptin treatment resulted in
      an increase in atherosclerosis (8.0+/-0.95% versus 5.4+/-0.59% lesion surface
      coverage; P<0.05). Leptin treatment also resulted in a shortened time to
      occlusive thrombosis after vascular injury (21+/-2.1 versus 34.6+/-5.4 minutes;
      P=0.045). CONCLUSIONS: These studies indicate that exogenous leptin promotes
      atherosclerosis and thrombosis and support the concept that elevations of leptin
      may increase the risk for cardiovascular disease.

PMID- 15947244
TI  - Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic
      dyslipidemia.
AB  - OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2
      in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS
      AND RESULTS: We used a novel multicompartmental model to simultaneously determine
      the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2
      after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the
      catabolism and transfer of the lipoprotein particles. Our results show that the
      overproduction of VLDL particles in DM2 is explained by enhanced secretion of
      VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by
      diabetes per se. The production rates of VLDL1 apoB and TG were closely related,
      as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ
      in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized
      particles was very similar in the 2 groups. Plasma glucose, insulin, and free
      fatty acids together explained 55% of the variation in VLDL1 TG production rate.
      CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic
      production of VLDL1 particles similar in size and composition to those in
      nondiabetic subjects. We propose that hyperglycemia is the driving force that
      aggravates overproduction of VLDL1 in DM2.

PMID- 15947245
TI  - Type 2 diabetic mice have increased arteriolar tone and blood pressure: enhanced
      release of COX-2-derived constrictor prostaglandins.
AB  - OBJECTIVE: Type 2 diabetes mellitus (T2-DM) is frequently associated with
      vascular dysfunction and elevated blood pressure, yet the underlying mechanisms
      are not completely understood. We hypothesized that in T2-DM, the regulation of
      peripheral vascular resistance is altered because of changes in local vasomotor
      mechanisms. METHODS AND RESULTS: In mice with T2-DM (C57BL/KsJ-(db-)/db-),
      systolic and mean arterial pressures measured by the tail cuff method were
      significantly elevated compared with those of control (db+/db-) animals (db/db,
      146+/-5 and 106+/-2 mm Hg versus control, 133+/-4 and 98+/-4 mm Hg, respectively;
      P<0.05). Total peripheral resistance, calculated from cardiac output values
      (measured by echocardiography) and mean arterial pressure were significantly
      elevated in db/db mice (db/db, 25+/-6 versus control, 15+/-1 mm Hg[middot]mL(
      1)[middot]min(-1)). In isolated, pressurized gracilis muscle arterioles (diameter
      approximately 80 microm) from db/db mice, stepwise increases in intraluminal
      pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in
      control vessels at each pressure step (at 80 mm Hg, db/db, 66+/-4% versus
      control, 79+/-3%). The passive diameters of arterioles (obtained in Ca2+-free
      solution) and the calculated myogenic index were not significantly different in
      the 2 groups. The presence of the prostaglandin H2/thromboxane A2 receptor
      antagonist SQ29548 did not affect arteriolar diameters of control mice but
      reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80
      mm Hg, 80+/-4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not
      affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2,
      caused a significant shift in the arteriolar pressure-diameter curve of vessels
      from db/db mice (at 80 mm Hg, 76+/-3%) but not in those of control mice. Also, in
      aortas of db/db mice, expression of COX-2 was enhanced compared with controls.
      CONCLUSIONS: Collectively, these findings suggest that in mice with T2-DM, the
      basal tone of skeletal muscle arterioles is increased because of an enhanced COX
      2-dependent production of constrictor prostaglandins. These alterations in
      microvascular prostaglandin synthesis may contribute to the increase in
      peripheral resistance and blood pressure in T2-DM.

PMID- 15947246
TI  - Platelet, not endothelial, P-selectin is required for neointimal formation after
      vascular injury.
AB  - BACKGROUND: P-selectin blockade significantly inhibits inflammation and
      neointimal formation after arterial injury; however, the independent roles of
      platelet and endothelial P-selectins in this process are unknown. In
      atherosclerosis, both platelet and endothelial cell P-selectins are important.
      This study was designed to determine whether P-selectin expression on platelet,
      endothelial, or both surfaces is critical to the inflammatory response and
      neointimal formation after arterial injury. METHODS AND RESULTS: Using wild-type
      (WT) and P-selectin-knockout (Psel(-/-)) mice, we performed bone marrow
      transplantation to generate chimeric mice that expressed either platelet P
      selectin (Plt-Psel) or endothelial P-selectin (EC-Psel). Double injury of the
      carotid artery was performed in these mice as well as in WT and Psel(-/-) mice.
      Animals were euthanized 4 or 21 days after arterial injury. Morphometric data
      showed that there was more neointimal formation in the WT mouse group when
      compared with the Psel(-/-) mouse group (0.015+/-0.004 vs 0.004+/-0.004 mm2,
      P<0.001). Further comparison showed significantly less neointimal area in EC-Psel
      mice (0.006+/-0.004 mm2) compared with Plt-Psel mice (0.011+/-0.005 mm2, P=0.026)
      and WT mice (0.015+/-0.004 mm2, P=0.001). No significant differences were
      observed between WT and Plt-Psel mice or between Psel(-/-) and EC-Psel mice.
      Decreased neointimal formation was accompanied by a reduced inflammatory
      response, as evidenced by immunostaining of RANTES and MCP-1 4 days after injury.
      CONCLUSIONS: Platelet P-selectin expression, but not endothelial P-selectin,
      plays a crucial role in the development of neointimal formation after arterial
      injury, and therapeutic strategies targeting leukocyte-platelet interactions
      could be effective in inhibiting restenosis.

PMID- 15947247
TI  - Ca2+ sparks and waves in canine purkinje cells: a triple layered system of Ca2+
      activation.
AB  - We have investigated the subcellular spontaneous Ca2+ events in canine Purkinje
      cells using laser scanning confocal microscopy. Three types of Ca2+ transient
      were found: (1) nonpropagating Ca2+ transients that originate directly under the
      sarcolemma and lead to (2) small Ca2+ wavelets in a region limited to 6-microm
      depth under the sarcolemma causing (3) large Ca2+ waves that travel throughout
      the cell (CWWs). Immunocytochemical studies revealed 3 layers of Ca2+ channels:
      (1) channels associated with type 1 IP3 receptors (IP3R1) and type 3 ryanodine
      receptors (RyR3) are prominent directly under the sarcolemma; (2) type 2
      ryanodine receptors (RyR2s) are present throughout the cell but virtually absent
      in a layer between 2 and 4 microm below the sarcolemma (Sub-SL); (3) type 3
      ryanodine receptors (RyR3) is the dominant Ca2+ release channel in the Sub-SL.
      Simulations of both nonpropagating and propagating transients show that the
      generators of Ca2+ wavelets differ from those of the CWWs with the threshold of
      the former being less than that of the latter. Thus, Purkinje cells contain a
      functional and structural Ca2+ system responsible for the mechanism that
      translates Ca2+ release occurring directly under the sarcolemma into rapid Ca2+
      release in the Sub-SL, which then initiates large-amplitude long lasting Ca2+
      releases underlying CWWs. The sequence of spontaneous diastolic Ca2+ transients
      that starts directly under the sarcolemma and leads to Ca2+ wavelets and CWWs is
      important because CWWs have been shown to cause nondriven electrical activity.

PMID- 15947248
TI  - Pre-B-cell colony-enhancing factor regulates NAD+-dependent protein deacetylase
      activity and promotes vascular smooth muscle cell maturation.
AB  - Conversion of vascular smooth muscle cells (SMCs) from a proliferative state to a
      nonproliferative, contractile state confers vasomotor function to developing and
      remodeling blood vessels. Using a maturation-competent human SMC line, we
      determined that this shift in phenotype was accompanied by upregulation of pre-B
      cell colony-enhancing factor (PBEF), a protein proposed to be a cytokine.
      Knockdown of endogenous PBEF increased SMC apoptosis and reduced the capacity of
      synthetic SMCs to mature to a contractile state. In keeping with these findings,
      human SMCs transduced with the PBEF gene had enhanced survival, an elongated
      bipolar morphology, and increased levels of h-caldesmon, smoothelin-A, smoothelin
      B, and metavinculin. Notwithstanding some prior reports, PBEF did not have
      attributes of a cytokine but instead imparted the cell with increased
      nicotinamide phosphoribosyltransferase activity. Intracellular nicotinamide
      adenine dinucleotide (NAD+) content was increased in PBEF-overexpressing SMCs and
      decreased in PBEF-knockdown SMCs. Furthermore, NAD+-dependent protein deacetylase
      activity was found to be essential for SMC maturation and was increased by PBEF.
      Xenotransplantation of human SMCs into immunodeficient mice revealed an increased
      capacity for PBEF-overexpressing SMCs to mature and intimately invest nascent
      endothelial channels. This microvessel chimerism and maturation process was
      perturbed when SMC PBEF expression was lowered. These findings identify PBEF as a
      regulator of NAD+-dependent reactions in SMCs, reactions that promote, among
      other potential processes, the acquisition of a mature SMC phenotype.

PMID- 15947249
TI  - CD31- but Not CD31+ cardiac side population cells exhibit functional
      cardiomyogenic differentiation.
AB  - Heart failure remains a leading cause of morbidity and mortality. The cellular
      mechanism underlying the development of cardiac dysfunction is a decrease in the
      number of viable cardiomyocytes. Recent observations have suggested that the
      adult heart may contain a progenitor cell population. Side population (SP) cells,
      characterized by a distinct Hoechst dye efflux pattern, have been shown to exist
      in multiple tissues and are capable of tissue-specific differentiation. In this
      report, we confirm the existence of a cardiac SP cell population,
      immunophenotypically distinct from bone marrow SP cells. Moreover, we demonstrate
      that among cardiac SP cells, the greatest potential for cardiomyogenic
      differentiation is restricted to cells negative for CD31 expression and positive
      for stem cell antigen 1 (Sca1) expression (CD31-/Sca1+). Furthermore, we
      determine that CD31-/Sca1+ cardiac SP cells are capable of both biochemical and
      functional cardiomyogenic differentiation into mature cardiomyocytes, with
      expression of cardiomyocyte-specific transcription factors and contractile
      proteins, as well as stimulated cellular contraction and intracellular calcium
      transients indistinguishable from adult cardiomyocytes. We also determine the
      necessity of cell-extrinsic signaling through coupling, although not fusion, with
      adult cardiomyocytes in regulating cardiomyogenic differentiation of cardiac SP
      cells. We, therefore, conclude that CD31-/Sca1+ cardiac SP cells represent a
      distinct cardiac progenitor cell population, capable of cardiomyogenic
      differentiation into mature cardiomyocytes through a process mediated by cellular
      coupling with adult cardiomyocytes.

PMID- 15947250
TI  - Atrial fibrillation in KCNE1-null mice.
AB  - Although atrial fibrillation is the most common serious cardiac arrhythmia, the
      fundamental molecular pathways remain undefined. Mutations in KCNQ1, one
      component of a sympathetically activated cardiac potassium channel complex, cause
      familial atrial fibrillation, although the mechanisms in vivo are unknown. We
      show here that mice with deletion of the KCNQ1 protein partner KCNE1 have
      spontaneous episodes of atrial fibrillation despite normal atrial size and
      structure. Isoproterenol abolishes these abnormalities, but vagomimetic
      interventions have no effect. Whereas loss of KCNE1 function prolongs ventricular
      action potentials in humans, KCNE1-/- mice displayed unexpectedly shortened
      atrial action potentials, and multiple potential mechanisms were identified: (1)
      K+ currents (total and those sensitive to the KCNQ1 blocker chromanol 293B) were
      significantly increased in atrial cells from KCNE1-/- mice compared with
      controls, and (2) when CHO cells expressing KCNQ1 and KCNE1 were pulsed very
      rapidly (at rates comparable to the normal mouse heart and to human atrial
      fibrillation), the sigmoidicity of IKs activation prevented current accumulation,
      whereas cells expressing KCNQ1 alone displayed marked current accumulation at
      these very rapid rates. Thus, KCNE1 deletion in mice unexpectedly leads to
      increased outward current in atrial myocytes, shortens atrial action potentials,
      and enhances susceptibility to atrial fibrillation.

PMID- 15947251
TI  - Unraveling the links between diabetes, obesity, and cardiovascular disease.

PMID- 15947252
TI  - Lymphangiogenesis in regenerating tissue: is VEGF-C sufficient?

PMID- 15947253
TI  - Six truisms concerning ACE and the renin-angiotensin system educed from the
      genetic analysis of mice.

PMID- 15947254
TI  - Matched case-control study on factor V Leiden and the prothrombin G20210A
      mutation in patients with ischemic stroke/transient ischemic attack up to the age
      of 60 years.
AB  - BACKGROUND AND PURPOSE: The role of the factor V Leiden mutation (FVL) and the
      G20210A mutation of the prothrombin (factor II [FII]) gene for arterial
      thrombosis is not clear. METHODS: We investigated the prevalence of these
      mutations in 468 patients with an acute stroke or transient ischemic attack (TIA)
      before the age of 60 years and in a healthy control population individually
      matched for age and gender. We also analyzed interactions between the mutations,
      gender, standard vascular risk factors, and stroke risk. RESULTS: The prevalence
      of the FVL did not differ significantly between patients and control subjects.
      However, we found a significant interaction between the FVL, smoking, and risk of
      stroke in women: female smokers without FVL had a somewhat increased risk of
      stroke of 2.6 (95% CI, 1.5 to 4.6; P=0.001) compared with nonsmoking noncarriers
      of the FVL. Stroke risk was markedly higher in female smokers who had the FVL
      (OR, 8.8; 95% CI, 2.0 to 38.0; P=0.004) after multivariate adjustment. No such
      interaction was observed in men. In contrast, the frequency of the FII G20210A
      mutation was significantly higher in male patients compared with controls (6%
      versus 1%; adjusted OR, 6.1; 95% CI, 1.3 to 28.3; P=0.021). In females, the
      prevalence of the mutation was 3% in both groups. We found no significant
      interactions of the FII G20210A mutation with other vascular risk factors and
      stroke risk. CONCLUSIONS: Our data indicate a highly increased risk of ischemic
      cerebrovascular events in women up to 60 years who smoke and have FVL. We also
      found evidence for an increased risk of stroke/TIA in men who have the FII
      G20210A mutation but not in women in this age group.

PMID- 15947256
TI  - Brain natriuretic peptide and early cardiac dysfunction after subarachnoid
      hemorrhage.

PMID- 15947255
TI  - Stroke presentation and outcome in developing countries: a prospective study in
      the Gambia.
AB  - BACKGROUND AND PURPOSE: Despite increasing burden of stroke in Africa,
      prospective descriptive data are rare. Our objective was to describe, in The
      Gambia, the clinical outcome of stroke patients admitted to the Royal Victoria
      Teaching Hospital in the capital Banjul, to assess mortality and morbidity, and
      propose preventive and therapeutic measures. METHODS: Prospective data were
      collected on consecutive patients older than 15 years old admitted between
      February 2000 and February 2001 with the diagnosis of nonsubarachnoid stroke.
      Risk factors, clinical characteristics, and social consequences were assessed
      using a modified National Institutes of Health Stroke Scale (mNIHSS), the Barthel
      Activity in Daily Living scale, the Siriraj score for subtypes, and the Bamford
      criteria for location/extension. Patients were followed-up at home up to 1 year
      after discharge. RESULTS: Ninety-one percent (148/162) of eligible patients were
      enrolled and followed-up. Hypertension and smoking were the most prevalent risk
      factors. Severity was high at admission, especially in women, and was strongly
      correlated to the outcome. mNIHSS and consciousness level on admission were
      strong predictors of the mortality risk. Swallowing difficulties at admission,
      fever, lung infection, and no aspirin treatment were, independently, risk factors
      for a lethal outcome susceptible to being addressed by treatment. Mortality was
      41% in-hospital and 62% after 1 year. In survivors, autonomy levels improved over
      time. Drug compliance was poor. At home, family members provided care. Long-term
      socioeconomic and cultural activities were affected in most patients.
      CONCLUSIONS: Case-fatality was high compared with Western cohorts. Preventive
      measures can be developed. Rational treatment, in the absence of head imaging for
      initial assessment, requires adapted protocols. Providers should be trained, both
      at hospital and community levels.

PMID- 15947257
TI  - The STICH trial: what does it tell us and where do we go from here?

PMID- 15947258
TI  - Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental
      subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Inflammation could play a role in cerebral vasospasm
      after subarachnoid hemorrhage (SAH). SP600125 a c-Jun N-terminal kinase (JNK)
      inhibitor reduces inflammation. The present study examined if SP600125 could
      reduce cerebral vasospasm. METHODS: Twenty-seven dogs were assigned to 5 groups:
      control, SAH, SAH plus dimethyl sulfoxide (DMSO), SAH plus SP600125 (10
      micromol/L), and SAH plus SP600125 (30 micromol/L). SAH was induced by the
      injection of autologous blood into the cisterna magna on day 0 and day 2.
      Angiograms were evaluated on day 0 and day 7. The behavior of the dogs was
      evaluated daily. The activation of the JNK pathway, the infiltration of
      leukocytes, and the production of cytokines were also evaluated. RESULTS: Severe
      vasospasm was observed in the basilar artery of SAH and DMSO dogs. The JNK
      signaling pathway was activated in the basilar artery after SAH and SP600125
      reduced angiographic and morphological vasospasm and improved behavior scores
      with a concomitant reduction of infiltrated leukocytes and IL-6 production.
      CONCLUSIONS: These results demonstrate that SP600125 attenuated cerebral
      vasospasm through a suppressed inflammatory response, which may provide a novel
      therapeutic target for cerebral vasospasm.

PMID- 15947259
TI  - Angiopoietin-2 facilitates vascular endothelial growth factor-induced
      angiogenesis in the mature mouse brain.
AB  - BACKGROUND AND PURPOSE: A better understanding of angiogenic factors and their
      effects on cerebral angiogenesis is necessary for the development of effective
      therapeutic strategies for ischemic brain injury. Vascular endothelial growth
      factor (VEGF) has been shown to induce angiogenesis in the adult mouse brain.
      However, the function of angiopoietin-2 (Ang-2) in cerebral angiogenesis has not
      been clarified. The goal of this study was to identify the combined effects of
      VEGF and Ang-2 on cerebral angiogenesis and the blood-brain barrier (BBB).
      METHODS: Six groups of 6 adult male CD-1 mice underwent AdlacZ (viral vector
      control), AdVEGF, AdAng2, VEGF protein, VEGF protein plus AdAng2, or saline
      (negative control) injection. Microvessels were counted using lectin staining on
      tissue sections after 2 weeks of treatment. Matrix metalloproteinase-9 (MMP-9)
      activity was determined by zymography. The presence of zonula occludens-1 (ZO-1)
      protein was determined by Western blot and immunohistochemistry. RESULTS: Mice
      treated with VEGF protein infusion plus AdAng-2 significantly increased
      microvessel counts relative to all other groups (P<0.05). The changes in MMP-9
      activity paralleled the reduced ZO-1 expression in the VEGF plus Ang-2-treated
      group compared with the other 5 groups (P<0.05). Double-labeled immunostaining
      demonstrated that ZO-1-positive staining was significantly decreased on the
      microvessel wall in the VEGF plus Ang-2-treated group. CONCLUSIONS: Our study
      demonstrates that the combination of VEGF and Ang-2 promotes more angiogenesis
      compared with VEGF alone. Furthermore, the combination of VEGF and Ang-2 may lead
      to BBB disruption because it increases MMP-9 activity and inhibits ZO-1
      expression.

PMID- 15947260
TI  - Predictors of early arterial reocclusion after tissue plasminogen activator
      induced recanalization in acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We aimed to determine clinical and hemodynamic predictors
      of early reocclusion (RO) in stroke patients treated with intravenous tissue
      plasminogen activator (tPA). METHODS: We studied 142 consecutive stroke patients
      with a documented middle cerebral artery (MCA) occlusion treated with intravenous
      tPA. All patients underwent carotid ultrasound and transcranial Doppler (TCD)
      examination before tPA bolus. National Institutes of Health Stroke Scale (NIHSS)
      scores were performed at baseline and serially for <24 hours. TCD monitoring of
      MCA recanalization (RE) and RO was performed during the first 2 hours after tPA
      bolus and repeated when clinical deterioration occurred <24 hours after
      documented RE in absence of intracranial hemorrhage. RESULTS: After 1 hour of tPA
      administration, RE occurred in 84 (61%) patients (53 partial, 31 complete). Of
      these, 21 (25%) patients worsened after an initial improvement and 17 (12%) of
      them showed RO on TCD. RO was identified at a mean time of 65+/-55 minutes after
      documented RE. RO was associated (P=0.034) with a lower degree of 24-hour NIHSS
      score improvement than sustained RE, and a higher modified Rankin scale score at
      3 months (P=0.002). Age older than 75 years (P=0.012), previous antiplatelet
      treatment (P=0.048), baseline NIHSS score >16 points (P=0.009), higher leukocytes
      count (P=0.042), beginning of RE <60 minutes after tPA bolus (P=0.039), and
      ipsilateral severe carotid stenosis/occlusion (P=0.001) were significantly
      associated with RO. In a logistic regression model, NIHSS score >16 at baseline
      (odds ratio [OR], 7.1; 95% CI, 1.3 to 32) and severe ipsilateral carotid disease
      (OR, 13.3; 95% CI, 3.2 to 54) remained as independent predictors of RO.
      CONCLUSIONS: Stroke severity and ipsilateral severe carotid artery disease
      independently predict RO after tPA-induced MCA RE.

PMID- 15947261
TI  - Prediction of the clinical outcome of pediatric moyamoya disease with
      postoperative basal/acetazolamide stress brain perfusion SPECT after
      revascularization surgery.
AB  - BACKGROUND AND PURPOSE: We evaluated whether basal/acetazolamide stress brain
      perfusion SPECT performed after revascularization surgery can predict the further
      clinical outcome of patients with pediatric moyamoya disease. METHODS: A total of
      77 (31 males, 46 females, age 6.6+/-3.2 years) patients with postoperative
      pediatric moyamoya disease who underwent basal/acetazolamide stress brain
      perfusion SPECT 6 to 12 months after revascularization surgery and who were
      followed-up >12 months after SPECT were included. Mean follow-up period after
      SPECT was 36+/-19 months. Sixty-two patients underwent bilateral ribbon
      encephaloduroarteriosynangiosis (EDAS), 14 bilateral EDAS, and 1 unilateral EDAS.
      Ordinal logistic regression analysis using 5 independent variables (infarction on
      preoperative MRI, age at the first operation, highest Suzuki stage on cerebral
      angiography, and regional cerebrovascular reserve on postoperative SPECT) against
      postoperative clinical outcomes was performed. RESULTS: Fifty-one patients had
      preserved reserve on postoperative SPECT and their clinical outcomes were
      excellent (30), good (15), fair (4), and poor (2); 26 patients had decreased
      reserve (excellent, 1; good, 7; fair, 14; poor, 4). On ordinal logistic
      regression analysis, age at the first operation (P=0.033) and reserve on
      postoperative SPECT (P<0.001) were statistically significant. CONCLUSIONS:
      Basal/acetazolamide stress brain perfusion SPECT performed at 6 to 12 months
      after the indirect bypass operation could predict the further clinical outcome of
      pediatric patients with moyamoya disease. Patients with decreased cerebrovascular
      reserve will have remaining neurological deficit and ischemic attacks on follow
      up.

PMID- 15947262
TI  - Transcranial low-frequency ultrasound-mediated thrombolysis in brain ischemia:
      increased risk of hemorrhage with combined ultrasound and tissue plasminogen
      activator: results of a phase II clinical trial.
AB  - BACKGROUND: Clinical studies using ultrasound at diagnostic frequencies in
      transcranial Doppler devices provided encouraging results in enhancing
      thrombolysis with tissue plasminogen activator (tPA) in acute stroke. Low
      frequency ultrasound does not require complex positioning procedures, penetrates
      through the skull better, and has been demonstrated to accelerate thrombolysis
      with tPA in animal experiments in wide cerebrovascular territories without
      hemorrhagic side effects. We therefore conducted the first multicenter clinical
      trial to investigate safety of tPA plus low-frequency ultrasound (300 kHz).
      METHODS: Acute stroke patients within a 6-hour time window were included
      (National Institutes of Health Stroke Scale scores >4). Magnetic resonance
      imaging (MRI) was used to document vascular occlusion and to rule out cerebral
      hemorrhage. Patients were allocated to combination therapy alternately; the first
      patient received tPA only, the second patient received tPA plus ultrasound, etc.
      Follow-up included serial MRI directly thereafter and 24 hours later to confirm
      recanalization and tissue imaging. Clinical recovery was measured after treatment
      and 3 months later. RESULTS: 26 patients (70.4+/-9.7 years) entered the trial (12
      tPA, 14 tPA plus ultrasound). The study was prematurely stopped because 5 of 12
      patients from the tPA only group but 13 of 14 patients treated with the tPA plus
      ultrasound showed signs of bleeding in MRI (P<0.01). Within 3 days of treatment,
      5 symptomatic hemorrhages occurred within the tPA plus ultrasound group. At 3
      months, neither morbidity nor treatment-related mortality or recanalization rates
      differed between both groups. CONCLUSIONS: This study demonstrated bioeffects
      from low-frequency ultrasound that caused an increased rate of cerebral
      hemorrhages in patients concomitantly treated with intravenous tPA.

PMID- 15947263
TI  - Factors influencing stroke survivors' quality of life during subacute recovery.
AB  - BACKGROUND AND PURPOSE: Health-related quality of life (HRQOL) is an important
      index of outcome after stroke and may facilitate a broader description of stroke
      recovery. This study examined the relationship of individual and clinical
      characteristics to HRQOL in stroke survivors with mild to moderate stroke during
      subacute recovery. METHODS: Two hundred twenty-nine participants 3 to 9 months
      poststroke were enrolled in a national multisite clinical trial (Extremity
      Constraint-Induced Therapy Evaluation). HRQOL was assessed using the Stroke
      Impact Scale (SIS), Version 3.0. The Wolf Motor Function Test documented
      functional recovery of the hemiplegic upper extremity. Multiple analysis of
      variance and regression models examined the influence of demographic and clinical
      variables across SIS domains. RESULTS: Age, gender, education level, stroke type,
      concordance (paretic arm=dominant hand), upper extremity motor function (Wolf
      Motor Function Test), and comorbidities were associated across SIS domains.
      Poorer HRQOL in the physical domain was associated with age, nonwhite race, more
      comorbidities, and reduced upper-extremity function. Stroke survivors with more
      comorbidities reported poorer HRQOL in the area of memory and thinking, and those
      with an ischemic stroke and concordance reported poorer communication.
      CONCLUSIONS: Although results may not generalize to lower functioning stroke
      survivors, individual characteristics of persons with mild to moderate stroke may
      be important to consider in developing comprehensive, targeted interventions
      designed to maximize recovery and improve HRQOL.

PMID- 15947264
TI  - Plasma B-type natriuretic peptide levels are associated with early cardiac
      dysfunction after subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: Serum B-type natriuretic peptide (BNP) is elevated after
      subarachnoid hemorrhage (SAH), as well as in the setting of congestive heart
      failure and myocardial infarction. The aim of this study was to prospectively
      quantify the relationship between BNP levels and cardiac outcomes after SAH.
      METHODS: Plasma was collected for BNP measurements as soon as possible after
      enrollment; a mean of 5+/-4 days after SAH symptom onset. On days 1, 3, and 6
      after enrollment, troponin I (cTi) was measured and 2-dimensional
      echocardiography was performed. The following cardiac variables were collected
      and treated dichotomously: left ventricular ejection fraction (LVEF), regional
      wall motion abnormalities (RWMA), diastolic dysfunction, pulmonary edema, and
      cTi. RESULTS: There were 57 subjects. The median BNP level was 141 pg/mL (range,
      0.8 to 3330 pg/mL). Higher mean BNP levels were present in those with RWMA (550
      versus 261 pg/mL; P=0.012), diastolic dysfunction (360 versus 44; P=0.011),
      pulmonary edema (719 versus 204; P=0.016), elevated cTi (662 versus 240;
      P=0.004), and LVEF <50% (644 versus 281; P=0.015). CONCLUSIONS: Early after SAH,
      elevated BNP levels are associated with myocardial necrosis, pulmonary edema, and
      both systolic and diastolic dysfunction of the left ventricle. These findings
      support the hypothesis that the heart releases BNP into the systemic circulation
      early after SAH.

PMID- 15947265
TI  - Measurement of community ambulation after stroke: current status and future
      developments.
AB  - BACKGROUND AND PURPOSE: This report considers the measurement of community
      ambulation for people with stroke. The conceptual issues underlying measurement
      of community ambulation are reviewed, and tests that measure either the task
      itself or at least some of its components are identified and discussed.
      CONCLUSIONS: The findings from this review suggest that although some progress
      has been made toward identifying community ambulation as a stand-alone entity,
      reliable and valid measures have not yet been developed. Gait speed, which is
      used often as a proxy measure for community ambulation, does not consistently
      reflect the level of community ambulation attained, and continued reliance on its
      use, particularly the 10-m timed walk, is misplaced. The limitations of the
      measures reviewed here point toward self-report as being the most useful outcome
      for current clinical use. However, this report highlights the need for research
      to first inform a theoretical framework for the measurement of community
      ambulation, from which a measurement tool or a battery of measurements can be
      developed and tested.

PMID- 15947266
TI  - Influenza vaccination is associated with a reduced risk of stroke.
AB  - BACKGROUND AND PURPOSE: Vascular death rates and hospitalizations for stroke are
      increased during influenza epidemics. Influenza vaccination may prevent stroke.
      We investigated whether influenza vaccination is associated independently with
      reduced odds of stroke and whether effects are confined to stroke subgroups and
      winter seasons and shared by other vaccinations. METHODS: During 18 months, we
      performed standardized interviews assessing vaccination status, risk factors,
      health-related behavior, and socioeconomic factors in 370 consecutive patients
      with ischemic or hemorrhagic stroke or transient ischemic attack (TIA) and 370
      age- and sex-matched control subjects selected randomly from the population.
      RESULTS: Influenza vaccination during the last vaccination campaign was less
      common in patients (19.2%) than control subjects (31.4%; P<0.0001). After
      adjustment for vascular risk factors, education, health-related behavior and
      other factors, influenza vaccination (odds ratio [OR], 0.46; 95% CI, 0.28 to
      0.77) but not other combined recent vaccinations (OR, 0.80; 95% CI, 0.42 to 1.43)
      were associated with reduced odds of stroke/TIA. Significant effects were found
      in men, older subjects (>65 years), subjects with previous vascular diseases, and
      regarding ischemic stroke; nonsignificant trends existed in women, younger
      subjects, and regarding hemorrhagic stroke. In etiologic subgroups of cerebral
      ischemia, similar effects were found. No protective effects were found during
      summer months; however, results also varied considerably between both winter
      seasons examined. CONCLUSIONS: These results support the hypothesis that
      influenza vaccination may be associated with reduced stroke risk. However,
      residual confounding cannot be excluded, and interventional studies are required
      to evaluate the role of influenza vaccination in stroke prevention.

PMID- 15947268
TI  - Arterial occlusive lesions recanalize more frequently in women than in men after
      intravenous tissue plasminogen activator administration for acute stroke.
AB  - BACKGROUND AND PURPOSE: Previous reports suggest that women achieve better
      outcome than men after intravenous thrombolysis for ischemic stroke. Coagulation
      and fibrinolysis differ between sexes. These findings prompted us to investigate
      possible gender differences in arterial recanalization after intravenous tissue
      plasminogen activator (IV tPA). METHODS: We identified 100 consecutive patients
      who presented with acute ischemic stroke and received IV tPA within 6 hours of
      onset. Only patients with large artery anterior circulation strokes, as
      determined by MRI/MRA or CT/CTA before treatment, who had follow-up vascular
      study within 72 hour after treatment were included. We compared demographics,
      clinical features, admission medications, symptom-to-needle and treatment-to
      repeat vascular imaging times, baseline National Institutes of Health Stroke
      Severity score, radiological and laboratory data, stroke mechanism, and outcome
      between the sexes. RESULTS: 39 patients met all inclusion/exclusion criteria (22
      men and 17 women). The recanalization rate was significantly higher in women (94%
      versus 59%; P=0.02). This difference remained statistically significant after
      excluding patients whose strokes were attributed to internal carotid artery
      occlusive lesions, and when the analysis was limited to those treated within 3
      hours of stroke onset. All other confounding variables did not differ
      significantly between the sexes. CONCLUSIONS: In our cohort, vascular occlusive
      lesions were more likely to recanalize in women than men in response to IV tPA.
      These preliminary findings need to be validated in larger prospective studies.

PMID- 15947270
TI  - Thrombotic risk factors in primary antiphospholipid syndrome: a 5-year
      prospective study.
AB  - BACKGROUND AND PURPOSE: Because thromboembolic events are frequently observed in
      primary antiphospholipid syndrome (PAPS), we assessed the risk factors for new
      thrombotic episodes. METHODS: Fifty-six PAPS patients (mean age, 37+/-10 years)
      were prospectively studied for 5 years. The preliminary Sapporo classification
      criteria for antiphospholipid syndrome (APS; a medium-high anticardiolipin
      antibody [aCL] titer and/or a positive lupus anticoagulant [LA] test in the
      presence of vascular thrombosis and/or pregnancy morbidity) were used to confirm
      the diagnosis. Thrombotic episodes or pregnancy losses before a diagnosis of PAPS
      were considered events, and any new disease manifestation other than
      thrombocytopenia was considered a recurrent event. Only patients with objectively
      verified thrombotic events were included in the study. RESULTS: Twenty-one new
      thrombotic events were observed in 15 subjects (26.8%), including 3 (5.4%) who
      died during the follow-up. The patients with IgG aCL levels of >40 IgG
      phospholipid unit (GPL-U) showed a higher incidence of new thrombotic events
      (43.3%) than those with levels of < or =40 GPL-U (7.7%). Univariate analysis
      identified a history of recurrent clinical events (P=0.004), a highly positive
      aCL titer (P=0.007), and the presence of cardiac abnormalities (P=0.036) as
      significant risk factors for new thrombotic events. A multivariate regression
      model confirmed that an IgG aCL titer of >40 GPL-U was an independent risk factor
      for thrombosis (odds ratio, 9.17; 95% confidence interval, 1.83 to 46.05).
      CONCLUSIONS: A high IgG aCL titer is the strongest predictor of new thrombotic
      events in PAPS patients.

PMID- 15947271
TI  - Avoiding central nervous system bleeding during antithrombotic therapy: recent
      data and ideas.
AB  - BACKGROUND: Approximately 7000 intracerebral hemorrhages (ICHs) annually in the
      US are caused by use of antithrombotic therapies. We review the incidence, risk
      factors, and predictors of ICH in patients receiving long-term anticoagulation or
      antiplatelet therapy. SUMMARY OF REVIEW: ICH rates range from 0.3% to 0.6% per
      year during oral anticoagulation in recent reports. Major risk factors are
      advanced patient age, elevated blood pressure, intensity of anticoagulation, and
      previous cerebral ischemia. Combining antiplatelet agents with anticoagulation
      and the combined use of aspirin plus clopidogrel appear to increase ICH risk.
      Modest blood pressure-lowering halves the frequency of ICH during antiplatelet
      therapy. CONCLUSIONS: ICH is an uncommon, but often fatal, complication of
      antithrombotic therapy that particularly afflicts patients with previous stroke.
      Recent data support that keeping international normalized ratio < or =3.0,
      control of hypertension, and avoiding the combination of aspirin with warfarin
      reduce its frequency.

PMID- 15947272
TI  - A matrix metalloproteinase protein array reveals a strong relation between MMP-9
      and MMP-13 with diffusion-weighted image lesion increase in human stroke.
AB  - BACKGROUND AND PURPOSE: Matrix metalloproteinases (MMPs) are involved in tissue
      destruction produced by the neuroinflammatory response that follows ischemic
      stroke. In the present study we use an MMP array to investigate the blood levels
      of several MMPs in stroke patients and its relation with brain tissue damage and
      neurological outcome. METHODS: Twenty-four patients with middle cerebral artery
      occlusion who received thrombolytic therapy were included. Blood samples were
      drawn before tissue plasminogen activator treatment and an MMP array (multiplex
      enzyme-linked immunosorbent assay [ELISA]) was performed including gelatinases
      (MMP-2 and MMP-9), collagenases (MMP-1, MMP-8, and MMP-13), stromelysines (MMP-3
      and MMP-10), and MMP endogen inhibitors (TIMP-1 and TIMP-2). To assess tissue
      lesion a serial multimodal MRI study was performed (pretreatment and at 24
      hours). RESULTS: Neither initial diffusion lesion nor hypoperfused volume was
      associated with metalloproteinase expression within the first 3 hours after
      stroke onset. Nevertheless, a strong correlation was found between MMP-9 and MMP
      13 with diffusion-weighted image (DWI) lesion expansion (r=0.54, P=0.05 and
      r=0.60, P=0.017, respectively). Baseline levels of both MMP-9 (OR, 14;95% CI, 1.5
      to 131; P=0.019) and MMP-13 (OR, 73; 95% CI, 3.9 to 1388; P=0.004) were
      independent predictors of final increase in brain infarct volume at 24 hours.
      CONCLUSIONS: Our results demonstrate that within the neuroinflammatory response,
      high levels of MMP-9 and MMP-13 are involved in DWI lesion growth despite
      thrombolytic therapy, suggesting its ultra-early role in brain injury.

PMID- 15947273
TI  - The Bayesian principle: can we adapt?

PMID- 15947274
TI  - Reorganization of motor execution rather than preparation in poststroke
      hemiparesis.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to examine movement
      related potentials (MRPs) in patients in the "chronic" stage after cortical
      stroke with recovered hemiparesis compared with healthy control subjects.
      METHODS: Right index finger MRPs were derived from 12 patients > or =1 year after
      infarction in the territory of the left middle cerebral artery as well as from 12
      control subjects. MRP components were compared between groups. RESULTS: In the
      patient group, the component directly preceding movement onset (negative slope
      [NS]) was significantly reduced over the lesioned hemisphere contralateral to the
      movement. Furthermore, increased motor potentials (MPs) were observed over the
      contralesional hemisphere during movement execution. No changes in the early MRP
      (Bereitschaftspotential) reflecting movement preparation were found. CONCLUSIONS:
      Because the NS is supposed to be generated by the primary motor cortex, the
      decreased component over the lesioned hemisphere is interpreted to represent
      impaired contralateral M1 functioning in stroke patients. Contralesional activity
      has been reported as a probable sign of brain plasticity by functional imaging
      studies. Our results broaden these findings, giving new insights into the
      temporal course of movement-related brain activity in recovered cortical stroke
      patients. The data point to a functional reorganization of motor execution rather
      than preparation in poststroke hemiparesis.

PMID- 15947275
TI  - Is Bayesian analysis ready for use in phase III randomized clinical trials?
      Beware the sound of the sirens.

PMID- 15947276
TI  - Clinical trials: is the Bayesian approach ready for prime time? Yes!

PMID- 15947277
TI  - Therapy implications of transthoracic echocardiography in acute ischemic stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Stroke is the third leading cause of death in most
      Western countries. Cardioembolism might be responsible for 15% to 20% of ischemic
      strokes. Although atrial fibrillation can be diagnosed by electrocardiography,
      the remaining causes of cardioembolic stroke are diagnosed by echocardiography.
      Recent recommendations on the management of acute ischemic stroke fail to
      consider echocardiography as an essential test in all patients. METHODS: We
      conducted a prospective observational study, performing transthoracic
      echocardiography on all patients admitted in our hospital with ischemic stroke,
      in sinus rhythm, from January 7, 2002, to October 16, 2003. Findings compatible
      with heart diseases that would indicate anticoagulation as beneficial were
      identified. RESULTS: Of the 853 patients admitted with ischemic stroke,
      transthoracic echocardiography was performed on 846 (99.2%). Of the 435 patients
      with ischemic stroke, in sinus rhythm, 37.2% had findings indicating
      anticoagulation as beneficial: dilated cardiopathy (19.1%), previous anterior
      wall myocardial infarction (6.2%), left ventricular systolic dysfunction with an
      ejection fraction <35% (3.7%), mitral valve stenosis with enlarged left atria
      (1.6%), intracardiac masses (0.5%), valvular prosthesis (0.2%), and >1
      abnormality (5.5%). CONCLUSIONS: In our study, transthoracic echocardiography had
      therapy implications in 37.2% of ischemic stroke patients in sinus rhythm.
      Transthoracic echocardiography should be considered an essential test in all
      ischemic stroke patients in sinus rhythm.

PMID- 15947278
TI  - Dose-related association of MTHFR 677T allele with risk of ischemic stroke:
      evidence from a cumulative meta-analysis.
AB  - BACKGROUND: Data are conflicting concerning ischemic stroke risk associated with
      a common polymorphism in the gene encoding 5,10-methylenetetrahydrofolate
      reductase (MTHFR 677C-->T), which predisposes to hyperhomocystinemia in vivo.
      METHODS: We performed a systematic review and meta-analysis of published relevant
      literature. We included cohort, case-control, or cross-sectional studies
      reporting the frequencies of heterozygous (CT) and homozygous (TT) genotypes in
      (a) all stroke/TIA (overall group) and (b) imaging-proven ischemic stroke (best
      phenotyped group). RESULTS: Among 14 870 subjects, the pooled estimated risk of
      stroke/TIA associated with the 677T allele increased in a dose-dependent manner
      (T allele pooled OR 1.17, 95%CI 1.09 to 1.26, TT genotype pooled OR 1.37, 95%CI
      1.15 to 1.64). An almost-identical relationship was observed when the analysis
      was restricted to imaging-proven ischemic stroke (T allele pooled OR 1.18, 95%CI
      1.09 to 1.29, TT genotype pooled OR 1.48, 95%CI 1.22 to 1.8). CONCLUSIONS: A
      graded increase in ischemic stroke risk with increasing MTHFR 677T allele dose
      was observed, suggesting an influence of this polymorphism as a genetic stroke
      risk factor and supporting other evidence indicating a causal relationship
      between elevated homocysteine and stroke.

PMID- 15947279
TI  - Long-term stability of improved language functions in chronic aphasia after
      constraint-induced aphasia therapy.
AB  - BACKGROUND AND PURPOSE: In response to the established notion that improvement of
      language functions in chronic aphasia only can be achieved through long-term
      treatment, we examined the efficacy of a short-term, intensive language training,
      constraint-induced aphasia therapy (CIAT). This program is founded on the
      learning principles of prevention of compensatory communication (constraint),
      massed practice, and shaping (induced). METHODS: Twenty-seven patients with
      chronic aphasia received 30 hours of training over 10 days. Twelve patients were
      trained with the CIAT program. For 15 patients the training included a module of
      written language and an additional training in everyday communication, which
      involved the assistance of family members (CIATplus). Outcome measures included
      standardized neurolinguistic testing and ratings of the quality and the amount of
      daily communication. RESULTS: Language functions improved significantly after
      training for both groups and remained stable over a 6-month follow-up period.
      Single case analyses revealed statistically significant improvements in 85% of
      the patients. Patients and relatives of both groups rated the quality and amount
      of communication as improved after therapy. This increase was more pronounced for
      patients of the group CIATplus in the follow-up. CONCLUSIONS: Results confirm
      that a short-term intense language training, based on learning principles, can
      lead to substantial and lasting improvements in language functions in chronic
      aphasia. The use of family and friends in the training provides an additional
      valuable element. This effective intervention can be successfully used in the
      rehabilitation of chronic aphasia patients. Additionally, its short-term design
      makes it economically attractive for service providers.

PMID- 15947281
TI  - Sodium/Proton exchanger 3 in the medulla oblongata and set point of breathing
      control.
AB  - RATIONALE: In vivo inhibition of the sodium/proton exchanger 3 (NHE3) in
      chemosensitive neurons of the ventrolateral brainstem augments central
      respiratory drive in anesthetized rabbits. OBJECTIVES: To further explore the
      possible role of this exchanger for the control of breathing, we examined the
      individual relationship between brainstem NHE3 abundance and ventilation in
      rabbits during wakefulness. METHODS: In 32 adult male rabbits on standard
      nutritional alkali load, alveolar ventilation, metabolic CO2 production, and
      blood gases were determined, together with arterial and urinary acid-base status
      and renal base control functions. Expression of NHE3 in brainstem tissue from the
      obex region was determined by quantitative real-time reverse-transcription
      polymerase chain reaction analysis. MEASUREMENTS AND MAIN RESULTS: Regarding the
      distribution above and below the median, we classified high and low brainstem
      NHE3 animals, expressing a mean (+/- SEM) NHE3 mRNA of 2.08 +/- 0.28 and 0.72 +/-
      0.06 fg cDNA/mg RNA, respectively. Alveolar ventilation of high brainstem NHE3
      animals was lower than that of low brainstem NHE3 animals (715 +/- 36 vs. 919 +/-
      41 ml . minute(-1); p < 0.01), a finding also reflected by a marked difference in
      Pa(CO2) (5.24 +/- 0.16 vs. 4.44 +/- 0.15 kPa; p < 0.01). Among possible secondary
      factors, CO2 production, systemic base excess, and fractional renal base
      reabsorption were not found to be different. CONCLUSIONS: We conclude that the
      level of brainstem NHE3 expression-most likely via intracellular pH modulation
      contributes to the individual control of breathing and Pa(CO2) in conscious
      rabbits by adjusting the set point and the loop gain of the system.

PMID- 15947280
TI  - Inflammatory basis of exercise-induced bronchoconstriction.
AB  - RATIONALE: Exercise-induced bronchoconstriction (EIB) is a highly prevalent
      condition with unclear pathogenesis. Two competing theories of the pathogenesis
      of EIB differ regarding the inflammatory basis of this condition. OBJECTIVES: Our
      goals were to establish whether epithelial cell and mast cell activation with
      release of inflammatory mediators occurs during EIB and how histamine and
      cysteinyl leukotriene antagonists alter the airway events occurring during EIB.
      METHODS: Induced sputum was used to measure mast cell mediators and eicosanoids
      at baseline and 30 minutes after exercise challenge in 25 individuals with asthma
      with EIB. In a randomized, double-blind crossover study, the cysteinyl
      leukotriene antagonist montelukast and antihistamine loratadine or two matched
      placebos were administered for two doses before exercise challenge. MAIN RESULTS:
      The percentage of columnar epithelial cells in induced sputum at baseline was
      associated with the severity of EIB. After exercise challenge, histamine,
      tryptase, and cysteinyl leukotrienes significantly increased and prostaglandin
      E(2) and thromboxane B(2) significantly decreased in the airways, and there was
      an increase in columnar epithelial cells in the airways. The concentration of
      columnar epithelial cells was associated with the levels of histamine and
      cysteinyl leukotrienes in the airways. Treatment with montelukast and loratadine
      inhibited the release of cysteinyl leukotrienes and histamine into the airways,
      but did not inhibit the release of columnar epithelial cells into the airways.
      CONCLUSIONS: These data indicate that epithelial cells, mast cell mediators, and
      eicosanoids are released into the airways during EIB, supporting an inflammatory
      basis for EIB.

PMID- 15947283
TI  - Adrenomedullin regenerates alveoli and vasculature in elastase-induced pulmonary
      emphysema in mice.
AB  - RATIONALE: Adrenomedullin, a potent vasodilator peptide, regulates cell growth
      and survival. However, whether adrenomedullin contributes to lung regeneration
      remains unknown. OBJECTIVES: To investigate whether adrenomedullin influences the
      kinetics of bone marrow cells, and whether adrenomedullin promotes regeneration
      of alveoli and vasculature and thereby improves lung structure and function in
      elastase-induced emphysema in mice. METHODS: Adrenomedullin or vehicle was
      randomly administered to C57BL/6 mice for 5 days. We counted the numbers of
      mononuclear cells and stem cell antigen-1-positive cells in circulating blood.
      After intratracheal injection of elastase or saline, mice were randomized to
      receive continuous infusion of adrenomedullin or vehicle for 14 days. Functional
      and histologic analyses were performed 28 days after treatment. RESULTS: Twenty
      eight days after elastase injection, destruction of the alveolar walls was
      observed. However, adrenomedullin infusion significantly inhibited the increase
      in lung volume, static lung compliance, and mean linear intercept in mice given
      elastase. Adrenomedullin increased the numbers of mononuclear cells and stem cell
      antigen-1-positive cells in circulating blood. Adrenomedullin significantly
      increased the number of bone marrow-derived cells incorporated into the elastase
      treated lung. Some of these cells were positive for cytokeratin or von Willebrand
      factor. Infusion of adrenomedullin after the establishment of emphysema also had
      beneficial effects on lung structure and function. In vitro, addition of
      adrenomedullin attenuates elastase-induced cell death in alveolar epithelial
      cells and endothelial cells. CONCLUSIONS: Adrenomedullin improved elastase
      induced emphysema at least in part through mobilization of bone marrow cells and
      the direct protective effects on alveolar epithelial cells and endothelial cells.

PMID- 15947282
TI  - Abnormalities in nitric oxide and its derivatives in lung cancer.
AB  - RATIONALE: A cellular prooxidant state promotes cells to neoplastic growth, in
      part because of modification of proteins and their functions. Reactive nitrogen
      species formed from nitric oxide (NO) or its metabolites, can lead to protein
      tyrosine nitration, which is elevated in lung cancer. OBJECTIVE: To determine the
      alteration in these NO derivatives and the role they may play in contributing to
      lung carcinogenesis. METHODS: We analyzed levels of NO, nitrite (NO2-), nitrate
      (NO3-), and the location of the protein nitration and identified the proteins
      that are modified. MEASUREMENTS AND MAIN RESULTS: Although exhaled NO and NO2-
      were increased, endothelial NO synthase or inducible NO synthase expression was
      similar in the tumor and tumor-free regions. However, immunohistochemistry showed
      that nitrotyrosine was increased in the tumor relative to non-tumor-bearing
      sections. We used proteomics to identify the modified proteins (two-dimensional
      polyacrylamide gel electrophoresis; mass spectrometry). Both the degree of
      nitration and the protein nitration profile were altered. We identified more than
      25 nitrated proteins, including metabolic enzymes, structural proteins, and
      proteins involved in prevention of oxidative damage. Alterations of the biology
      of NO metabolites and nitration of proteins may contribute to the mutagenic
      processes and promote carcinogenesis. CONCLUSIONS: This study provides evidence
      in favor of a role for reactive nitrogen and oxygen species in lung cancer.

PMID- 15947284
TI  - Hypoxia impairs systemic endothelial function in individuals prone to high
      altitude pulmonary edema.
AB  - RATIONALE: High-altitude pulmonary edema (HAPE) is characterized by excessive
      pulmonary vasoconstriction and is associated with decreased concentrations of
      nitric oxide (NO) in the lung. OBJECTIVES: We hypothesized that individuals
      susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO
      vasodilator pathway during hypoxia in the systemic vasculature. METHODS: During
      normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12,
      corresponding to an altitude of 4,500 m above sea level) endothelium-dependent
      and endothelium-independent vasodilator responses to intraarterial infusion of
      acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by
      forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE
      resistant control subjects. MAIN RESULTS: Pulmonary artery systolic pressure
      increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control
      subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001).
      Despite similar responses during normoxia in both groups, ACh-induced changes in
      forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p =
      0.01) but not in control subjects. The attenuated vascular response to ACh
      infusion during hypoxia inversely correlated with increased pulmonary artery
      systolic pressure (p = 0.04) and decreased plasma nitrite correlated with
      attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). CONCLUSIONS:
      Hypoxia markedly impairs vascular endothelial function in the systemic
      circulation in HAPE-S subjects due to a decreased bioavailability of NO.
      Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary
      vasoconstriction that is central to the pathogenesis of HAPE.

PMID- 15947285
TI  - Sildenafil improves alveolar growth and pulmonary hypertension in hyperoxia
      induced lung injury.
AB  - RATIONALE: Bronchopulmonary dysplasia (BPD), the chronic lung disease of preterm
      infants, and pulmonary emphysema, both significant global health problems, are
      characterized by an arrest in alveolar growth/loss of alveoli structures.
      Mechanisms that inhibit distal lung growth are poorly understood, but recent
      studies suggest that impaired vascular endothelial growth factor signaling and
      reduced nitric oxide (NO) production decreases alveolar and vessel growth in the
      developing lung, features observed in experimental oxygen-induced BPD. NO exerts
      its biological activity by stimulating guanosine 3',5'-cyclic monophosphate
      (cGMP) production. OBJECTIVES: Because cGMP is inactivated by phosphodiesterase
      (PDE) enzymes, we hypothesized that the cGMP-specific PDE5 inhibitor sildenafil
      would promote angiogenesis and attenuate oxygen-induced lung injury in newborn
      rats. METHODS, MEASUREMENTS, AND MAIN RESULTS: In vitro, sildenafil (10(-4) M)
      increased endothelial capillary network formation of human pulmonary endothelial
      cells exposed to hyperoxia. In vivo, rat pups were randomly exposed from birth to
      normoxia, hyperoxia (95% O(2), BPD model), and hyperoxia+sildenafil (100
      mg/kg/day subcutaneously). Rat pups exposed to hyperoxia showed fewer and
      enlarged air spaces as well as decreased capillary density, mimicking pathologic
      features seen in human BPD. These structural anomalies were associated with
      echographic (decreased pulmonary acceleration time) and structural (right
      ventricular hypertrophy and increased medial wall thickness) signs of pulmonary
      hypertension. Sildenafil preserved alveolar growth and lung angiogenesis, and
      decreased pulmonary vascular resistance, right ventricular hypertrophy and medial
      wall thickness. CONCLUSIONS: Our findings suggest a role for the NO/cGMP pathway
      during alveolar development. Sildenafil may have therapeutic potential in
      diseases associated with impaired alveolar structures.

PMID- 15947287
TI  - 3p microsatellite alterations in exhaled breath condensate from patients with non
      small cell lung cancer.
AB  - The still-high mortality for lung cancer urgently requires the availability of
      new, noninvasive diagnostic tools for use in early diagnosis and screening
      programs. Recently, exhaled breath condensate (EBC) has been proposed as a useful
      tool to obtain biological information on lung cancer disease. This study
      provides, for the first time, evidence that DNA alterations already described in
      lung cancer are detectable in EBC from patients with non-small cell lung cancer
      (NSCLC) and in healthy subjects. Thirty patients with histologic evidence of
      NSCLC and 20 healthy subjects were enrolled in the present study. All subjects
      had allelotyping analysis of DNA from EBC (EBC-DNA) and from whole blood (WB-DNA)
      of a selected panel of five microsatellites (D3S2338, D3S1266, D3S1300, D3S1304,
      D3S1289) located in chromosomal region 3p. Results from healthy subjects and
      subjects with cancer, and from EBC and WB, were compared. In addition, the
      relationships with smoking habit and clinicopathologic tumor features were
      considered. Microsatellite alterations (MAs) were found in 53% of EBC-DNA and in
      10% of WB-DNA loci investigated in patients with NSCLC (p < 10(-6)); conversely,
      MAs were present only in 13% of EBC-DNA and in 2% of WB-DNA informative loci in
      healthy subjects. In patients with NSCLC, a direct association between number of
      MAs detected in EBC-DNA and tobacco consumption was observed. We conclude that
      EBC-DNA is highly sensitive in detecting MA information unique to patients with
      lung cancer. Furthermore, MA information seems to be directly related with
      tobacco consumption, and is potentially applicable to screening and early
      diagnostic programs for patients with NSCLC.

PMID- 15947288
TI  - Reversibility of airflow obstruction by hypoglossus nerve stimulation in
      anesthetized rabbits.
AB  - RATIONALE: Anesthesia-induced uncoupling of upper airway dilating and inspiratory
      pump muscles activation may cause inspiratory flow limitation, thereby mimicking
      obstructive sleep apnea/hypopnea. OBJECTIVES: Determine whether inspiratory flow
      limitation occurs in spontaneously breathing anesthetized rabbits and whether
      this can be reversed by direct hypoglossal nerve stimulation and by the
      application of continuous positive airway pressure. METHODS: Ten New Zealand
      White rabbits were anesthetized, instrumented, and studied supine while breathing
      spontaneously at ambient pressure or during the application of positive or
      negative airway pressure. Under each of these conditions, the effect of
      unilateral or bilateral hypoglossal nerve stimulation was investigated.
      MEASUREMENTS: Inspiratory flow and tidal volume were measured together with
      esophageal pressure and the electromyographic activity of diaphragm, alae nasi,
      and genioglossus muscles. MAIN RESULTS: Anesthesia caused a marked increase in
      inspiratory resistance, snoring, and in eight rabbits, inspiratory flow
      limitation. Hypoglossus nerve stimulation was as effective as continuous positive
      airway pressure in reversing inspiratory flow limitation and snoring. Its
      effectiveness increased progressively as airway opening pressure was lowered,
      reached a maximum at -5 cm H2O, but declined markedly at lower pressures. With
      negative airway opening pressure, airway collapse eventually occurred during
      inspiration that could be prevented by hypoglossus nerve stimulation. The
      recruitment characteristics of hypoglossus nerve fibers was steep, and
      significant upper airway dilating effects already obtained with stimulus
      intensities 36 to 60% of maximum. CONCLUSION: This study supports hypoglossus
      nerve stimulation as a treatment option for obstructive sleep apnea.

PMID- 15947286
TI  - Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug
      resistance patterns.
AB  - RATIONALE: Multiple infections with different strains of Mycobacterium
      tuberculosis may occur in settings where the infection pressure is high. The
      relevance of mixed infections for the patient, clinician, and control program
      remains unclear. OBJECTIVES: This study aimed to describe reinfection and mixed
      infection as underlying mechanisms of changing drug-susceptibility patterns in
      serial sputum cultures. METHODS: Serial M. tuberculosis sputum cultures from
      patients diagnosed with multi-drug-resistant (MDR) tuberculosis were evaluated by
      phenotypic drug-susceptibility testing and mutation detection methods. Genotypic
      analysis was done by IS6110 DNA fingerprinting and a novel strain-specific
      polymerase chain reaction amplification method. MEASUREMENTS AND MAIN RESULTS:
      DNA fingerprinting analysis of serial sputum cultures from 48 patients with MDR
      tuberculosis attributed 10 cases to reinfection and 1 case to mixed infection. In
      contrast, strain-specific polymerase chain reaction amplification analysis in 9
      of the 11 cases demonstrated mixed infection in 5 cases, reinfection in 3 cases,
      and laboratory contamination in 1 case. Analysis of clinical data suggests that
      first-line therapy can select for a resistant subpopulation, whereas poor
      adherence or second-line therapy resulted in the reemergence of the drug
      susceptible subpopulations. CONCLUSIONS: We have shown that, in some patients
      with MDR tuberculosis, mixed infection may be responsible for observations
      attributed to reinfection by DNA fingerprinting. We conclude that treatment and
      adherence determines which strain is dominant. We hypothesize that treatment with
      second-line drugs may lead to reemergence of the drug-susceptible strain in
      patients with mixed infection.

PMID- 15947289
TI  - Superoxide dismutase improves gas exchange and pulmonary hemodynamics in
      premature lambs.
AB  - RATIONALE: Oxidant stress may increase the severity of respiratory distress
      syndrome (RDS) after premature birth by altering vasoreactivity and increasing
      lung edema, but the acute effects of superoxide dismutase (SOD) treatment on gas
      exchange, lung compliance (CL), and pulmonary vascular resistance in premature
      animals with RDS are unknown. OBJECTIVE: We studied the effects of intratracheal
      recombinant human SOD treatment (rhSOD) on gas exchange, CL, and pulmonary
      hemodynamics in 46 premature lambs with RDS. METHODS: After C-section delivery,
      lambs were randomly assigned to treatment with SOD (2.5-10 mg/kg) with or without
      inhaled nitric oxide (iNO, 5 ppm), and mechanically ventilated for 4 hours. At
      the end of the study, pressure-volume curves and wet-dry lung weights were
      measured to assess CL and edema, respectively. MAIN RESULTS: Despite an initial
      rise in Pa(O(2)), Pa(O(2)) in control animals progressively declined over the 4
      hour treatment period (Pa(O(2)) = 25.0 +/- 7.5 mm Hg at 4 hours). In comparison
      with control animals, early treatment with SOD at 5 and 10 mg/kg improved
      Pa(O(2)) at 4 hours (167 +/- 44 and 269 +/- 33 mm Hg, respectively; p < 0.05 vs.
      control), but did not decrease lung edema or improve CL. In contrast, late
      treatment with SOD did not improve Pa(O(2)). Treatment with iNO increased
      Pa(O(2)) (196 +/- 22 vs. 25 +/- 8 mm Hg, control animals; p < 0.01), but the
      response to iNO was not augmented by combined therapy (SOD + iNO). After 4 hours
      of ventilation with FI(O(2)) = 1.00, rhSOD treatment lowered pulmonary vascular
      resistance compared with control animals. CONCLUSIONS: Early intratracheal rhSOD
      treatment improves oxygenation in premature lambs with RDS and prevents the
      development of pulmonary hypertension.

PMID- 15947290
TI  - Smoking cessation before lung resection.

PMID- 15947291
TI  - Bleeding risk and bronchoscopy: in search of the evidence in evidence-based
      medicine.

PMID- 15947292
TI  - Listening to our patients.

PMID- 15947293
TI  - Does lung volume reduction surgery really improve bone mineral density?

PMID- 15947294
TI  - Appropriate management of respiratory problems is of utmost importance in the
      treatment of patients with amyotrophic lateral sclerosis.

PMID- 15947295
TI  - Immune stimulation in sepsis: to be or not to be?

PMID- 15947296
TI  - Recognition and communication: essential elements to improving end-of-life care.

PMID- 15947297
TI  - Topical hemostatic tamponade: another tool in the treatment of massive
      hemoptysis.

PMID- 15947298
TI  - Unique solitary small cell lung cancer: need for histologic examination.

PMID- 15947299
TI  - Development and validation of a survey-based COPD severity score.
AB  - OBJECTIVE: To develop a comprehensive disease-specific COPD severity instrument
      for survey-based epidemiologic research. STUDY DESIGN AND SETTING: Using a
      population-based sample of 383 US adults with self-reported physician-diagnosed
      COPD, we developed a disease-specific COPD severity instrument. The severity
      score was based on structured telephone interview responses and included five
      overall aspects of COPD severity: respiratory symptoms, systemic corticosteroid
      use, other COPD medication use, previous hospitalization or intubation, and home
      oxygen use. We evaluated concurrent validity by examining the association between
      the COPD severity score and three health status domains: pulmonary function,
      physical health-related quality of life (HRQL), and physical disability.
      Pulmonary function was available for a subgroup of the sample (FEV1, n = 49; peak
      expiratory flow rate [PEFR], n = 93). RESULTS: The COPD severity score had high
      internal consistency reliability (Cronbach alpha = 0.80). Among the 49 subjects
      with FEV1 data, higher COPD severity scores were associated with poorer
      percentage of predicted FEV1 (r = - 0.40, p = 0.005). In the 93 subjects with
      available PEFR measurements, greater COPD severity was also related to worse
      percentage of predicted PEFR (r = - 0.35, p < 0.001). Higher COPD severity scores
      were strongly associated with poorer physical HRQL (r = - 0.58, p < 0.0001) and
      greater restricted activity attributed to a respiratory condition (r = 0.59, p <
      0.0001). Higher COPD severity scores were also associated with a greater risk of
      difficulty with activities of daily living (odds ratio [OR], 2.3; 95% confidence
      interval [CI], 1.8 to 3.0) and inability to work (OR, 4.2; 95% CI, 3.0 to 5.8).
      CONCLUSION: The COPD severity score is a reliable and valid measure of disease
      severity, making it a useful research tool. The severity score, which does not
      require pulmonary function measurement, can be used as a study outcome or to
      adjust for disease severity.

PMID- 15947300
TI  - Early changes of cardiac structure and function in COPD patients with mild
      hypoxemia.
AB  - BACKGROUND: COPD is often associated with changes of the structure and the
      function of the heart. Although functional abnormalities of the right ventricle
      (RV) have been well described in COPD patients with severe hypoxemia, little is
      known about these changes in patients with normoxia and mild hypoxemia. STUDY
      OBJECTIVES: To assess the structural and functional cardiac changes in COPD
      patients with normal Pa(O2) and without signs of RV failure. METHODS: In 25
      clinically stable COPD patients (FEV1, 1.23 +/- 0.51 L/s; Pa(O2), 82 +/- 10 mm Hg
      [mean +/- SD]) and 26 age-matched control subjects, the RV and left ventricular
      (LV) structure and function were measured by MRI. Pulmonary artery pressure (PAP)
      was estimated from right pulmonary artery distensibility. RESULTS: RV mass
      divided by RV end-diastolic volume as a measure of RV adaptation was 0.72 +/-
      0.18 g/mL in the COPD group and 0.41 +/- 0.09 g/mL in the control group (p <
      0.01). LV and RV ejection fractions were 62 +/- 14% and 53 +/- 12% in the COPD
      patients, and 68 +/- 11% and 53 +/- 7% in the control subjects, respectively. PAP
      estimated from right pulmonary artery distensibility was not elevated in the COPD
      group. CONCLUSION: From these results, we conclude that concentric RV hypertrophy
      is the earliest sign of RV pressure overload in patients with COPD. This
      structural adaptation of the heart does not alter RV and LV systolic function.

PMID- 15947301
TI  - Survival of chronic hypercapnic COPD patients is predicted by smoking habits,
      comorbidity, and hypoxemia.
AB  - STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated
      with a poor prognosis. We hypothesized that, within this group of chronic
      hypercapnic COPD patients, factors that could mediate this hypercapnia, such as
      decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum
      expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response
      (HCVR), could be related to survival. Other parameters, such as arterial blood
      gas values, airway obstruction (FEV1), body mass index (BMI), current smoking
      status, and the presence of comorbidity were studied as well. METHODS: A cohort
      of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3
      weeks) in our institute was followed up for 3.8 years on average. Survival was
      analyzed using a Cox proportional hazards model. The risk factors considered were
      analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis
      18 patients (10 male) were deceased. After adjusting for age and gender,
      P(I(max)), P(E(max)), and HCVR were not correlated with survival within this
      hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence
      interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7
      to 18.7) were associated with increased mortality. A higher Pa(O2) affected
      survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to
      be lower in survivors, but this did not reach statistical significance (HR, 2.0
      per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related
      with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic
      hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level
      are significantly associated with survival. Airway obstruction, age, and BMI are
      known to be predictors of survival in COPD patients in general. However, these
      parameters do not seem to significantly affect survival once chronic hypercapnia
      has developed.

PMID- 15947302
TI  - Nitrosative stress, heme oxygenase-1 expression and airway inflammation during
      severe exacerbations of COPD.
AB  - STUDY OBJECTIVES: The aim of this study was to examine the relationship between
      airway inflammation, nitrosative stress, heme-oxygenase expression, and acute
      severe exacerbations of COPD. DESIGN: We measured heme oxygenase (HO)-1,
      inducible nitric oxide (NO) synthase expression and nitrotyrosine formation, as
      well as eosinophilic cationic protein, myeloperoxidase (MPO), interleukin (IL-8),
      and granulocyte macrophage-colony stimulating factor levels in induced sputum
      samples from 12 COPD patients (mean +/- SD; FEV1 40 +/- 14% predicted) at the
      onset of an acute severe exacerbation of COPD requiring hospital admission and 16
      weeks after remission. RESULTS: We demonstrated increased percentages (p = 0.001)
      and absolute numbers (p = 0.028) of total nitrotyrosine positive (+ve)
      inflammatory cells (ie, polymorphonuclear cells and macrophages), increased
      percentages (p = 0.04) and absolute numbers (p = 0.05) of total HO-1 +ve
      inflammatory cells, and increased MPO (p = 0.005) and IL-8 levels (p = 0.028)
      during severe exacerbation compared with the stable state. CONCLUSIONS: Our
      results support the hypothesis of an involvement of inflammatory and nitrosative
      stress in severe COPD exacerbations. Future therapeutic strategies may aim at
      regulating inflammation and NO synthesis during COPD exacerbations.

PMID- 15947303
TI  - A comparison of airway and serum matrix metalloproteinase-9 activity among normal
      subjects, asthmatic patients, and patients with asthmatic mucus hypersecretion.
AB  - BACKGROUND: The rate of decline in lung function is increased in asthmatic
      patients, particularly in those with coexisting asthmatic mucus hypersecretion
      (AMH), in whom inflammation and the activity of matrix metalloproteinase (MMP)-9
      and tissue inhibitor of metalloproteinase (TIMP)-1 in serum and BAL fluid (BALF)
      may be increased. METHODS: Seven nonasthmatic subjects and 22 asthmatic subjects
      completed a questionnaire, and underwent lung function testing and bronchoscopy,
      during which AMH was diagnosed by the presence of mucus plugging. Subjects were
      classified as follows: mild/moderate asthma; severe asthma; and AMH. In BALF, we
      measured the differential WBC counts and MMP-9 activity by zymography. We
      measured total MMP-9 and TIMP-1 activity by enzyme-linked immunosorbent assay in
      BALF and serum. RESULTS: The mean (+/- confidence interval) FEV1 was lower in AMH
      patients (73 +/- 13% predicted) compared with nonasthmatic subjects (95 +/- 7%)
      and patients with mild/moderate asthma (73 +/- 9%; p < 0.05), and was similar to
      that of patients with severe asthma (80 +/- 20%). MMP-9 activity was greater in
      AMH patients and in patients with severe asthma compared with nonasthmatic
      subjects (p = 0.05 and p = 0.01, respectively), as were TIMP-1 activities (p =
      0.001 and p = 0.04, respectively), but MMP-9/TIMP-1 ratios were not. MMP-9
      activity increased across the four groups from nonasthmatic subjects to AMH
      patients (r = 0.58; p = 0.0009), but the differential and total WBC counts were
      similar. There were no relationships between FEV1 percent predicted and either
      MMP-9 activity or MMP-9/TIMP-1 ratio. There were no differences in serum MMP-9
      activity, which did not correlate with MMP-9 activity in BALF. CONCLUSIONS: AMH
      and severe asthma were associated with greater proteolytic enzyme activities
      despite similar airway inflammation, which might play a role in remodeling and
      accelerated the decline in lung function in these patients.

PMID- 15947304
TI  - The incidence of asthma in young adults.
AB  - STUDY OBJECTIVES: Longitudinal data on adult asthma are sparse. The objectives of
      this study were to determine the incidence of asthma and to establish the risk
      factors for the development of asthma in subjects who were 12 to 41 years old
      over an 8-year period. DESIGN: From birth cohorts over the period 1953 to 1982 in
      The Danish Twin Registry, 19,349 subjects with no history of asthma, as
      determined by a questionnaire-based survey in 1994, answered a follow-up
      questionnaire in 2002. The subjects were regarded as incident asthma cases when
      answering "yes" to the question "Do you have, or have you ever had asthma?" in
      2002, and "no" to the same question in 1994. RESULTS: A total of 838 cases (4.3%)
      of new asthma were identified in 2002. The incidence rates of asthma were 4.5 and
      6.4 per 1,000 person-years, respectively, among male and female subjects. For all
      ages, the probability of adult-onset asthma was greater for female subjects (odds
      ratio [OR], 1.49; p < 0.001), and for both sexes there was a slow decline in
      probability with increasing age. There was a positive association between
      increasing body mass index (BMI) and risk of adult-onset asthma applying to both
      sexes (OR, 1.05 per unit; p < 0.001). Furthermore, positive associations were
      found between incident asthma and a history of hay fever (OR: male subjects, 4.2;
      female subjects, 3.7; p < 0.001), eczema (OR: male subjects, 3.5; female
      subjects, 2.0; p < 0.001), and both (OR: male subjects, 6.9; female subjects,
      8.0; p < 0.001). CONCLUSIONS: There is a continuing high incidence of asthma past
      childhood that is most pronounced among female subjects. Increasing levels of BMI
      are associated with a greater likelihood of developing asthma for both sexes. A
      substantial portion of cases of adult asthma is preceded by upper airway allergic
      symptoms and/or eczema, thus indicating a shared pathogenesis.

PMID- 15947305
TI  - Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in
      endurance athletes.
AB  - BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been
      reported in endurance athletes, its underlying mechanisms and consequences during
      exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to
      assess the following: (1) bronchial responsiveness to methacholine and to
      exercise; (2) airway inflammation; and (3) airflow limitation during intense
      exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional
      observational study. SETTING: Lung function and exercise laboratory at a
      university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes
      and 13 sedentary control subjects were explored for the following: (1) self
      reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to
      methacholine and exercise; (3) airflow limitation during intense exercise; and
      (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation.
      RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in
      association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/-
      8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs
      14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of
      atopy, and more exercise-induced symptoms compared with non-hyperresponsive
      athletes and control subjects (p < 0.05). Furthermore, airflow limitation during
      intense exercise was observed in eight athletes, among whom five had BHR.
      Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC
      ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and
      29%, respectively, lower compared with those of nonlimited athletes (p < 0.05).
      CONCLUSION: BHR in endurance athletes was associated with the criteria of
      eosinophilic airway inflammation and atopy, whereas airflow limitation during
      exercise was primarily a consequence of decreased resting spirometric values.
      Both BHR and bronchial obstruction at rest with subsequent expiratory flow
      limitation during exercise may promote respiratory symptoms during exercise in
      athletes.

PMID- 15947306
TI  - Respiratory complaints in Chinese: cultural and diagnostic specificities.
AB  - STUDY OBJECTIVES: We investigated the qualitative components of a wide range of
      Chinese descriptors of dyspnea and associated symptoms, and their relevance for
      clinical diagnosis. MEASUREMENTS: Sixty-one spontaneously reported descriptors
      were elicited in Chinese patients to make a symptom checklist, which was
      administered to new groups of patients with different cardiopulmonary diseases,
      to patients with medically unexplained dyspnea and to healthy subjects. RESULTS:
      Test-retest reliability was satisfactory for most of the descriptors. A principal
      component analysis on 61 descriptors yielded the following eight factors: dyspnea
      effort of breathing; dyspnea-affective aspect; wheezing; anxiety; tingling;
      palpitation; coughing and sputum; and dying experience. Although the descriptors
      of dyspnea-effort of breathing resembled Western wordings and were shared by
      patients with a variety of diseases, the descriptors of dyspnea-affective aspect
      appeared to be more culturally specific and were primarily linked to the
      diagnosis of medically unexplained dyspnea, whereas wheezing was specifically
      linked to asthma. CONCLUSIONS: Three factors of breathlessness were found in
      Chinese. The descriptors of dyspnea-effort of breathing and wheezing appear to be
      similar to Western descriptors, whereas the dyspnea-affective aspect seems to
      bear cultural specificity.

PMID- 15947307
TI  - The relationship between reduced lung function and cardiovascular mortality: a
      population-based study and a systematic review of the literature.
AB  - STUDY OBJECTIVES: Conditions that give rise to reduced lung function are
      frequently associated with low-grade systemic inflammation, which may lead to
      poor cardiovascular outcomes. We sought to determine the relationship between
      reduced FEV1 and cardiovascular mortality, independent of smoking. DESIGN:
      Longitudinal population-based study and a meta-analysis of literature. SETTING:
      Representative sample of the general population. PARTICIPANTS: Participants of
      the first National Health and Nutrition Examination Survey Epidemiologic Follow
      up Study who were 40 to 60 years of age at baseline assessment (n = 1,861).
      MEASUREMENTS AND RESULTS: We compared the risk of cardiovascular mortality across
      quintiles of FEV1. Individuals in the lowest FEV1 quintile had the highest risk
      of cardiovascular mortality (relative risk [RR], 3.36; 95% confidence interval
      [CI], 1.54 to 7.34). Compared to FEV1 quintile 1, individuals in quintile 5 had a
      fivefold increase in the risk of death from ischemic heart disease (RR, 5.65; 95%
      CI, 2.26 to 14.13). We also performed a systematic review of large cohort studies
      (> 500 participants) that reported on the relationship between FEV1 and
      cardiovascular mortality (12 studies; n = 83,880 participants). Compared to
      participants in the highest FEV1 category, those with reduced FEV1 had a higher
      risk of cardiovascular mortality (pooled RR, 1.77; 95% CI, 1.56 to 1.97).
      CONCLUSIONS: There is strong epidemiologic evidence to indicate that reduced FEV1
      is a marker for cardiovascular mortality independent of age, gender, and smoking
      history.

PMID- 15947308
TI  - Bone mineral density improvement after lung volume reduction surgery for severe
      emphysema.
AB  - BACKGROUND: In patients with severe emphysema, bone mineral density (BMD) is
      reduced and the risk of osteoporosis is increased. STUDY OBJECTIVES: To identify
      the impact of lung volume reduction surgery on BMD. DESIGN: Prospective cohort
      study. SETTING: University hospital. PATIENTS AND INTERVENTIONS: Forty
      emphysematous patients, all receiving oral steroid therapy, underwent bilateral
      lung volume reduction surgery. Thirty similar patients, who refused the
      operation, followed a standard respiratory rehabilitation program. MEASUREMENTS:
      All subjects were evaluated pretreatment and 12 months posttreatment for
      respiratory function, nutritional status, and bone-related biochemical
      parameters. BMD was assessed by dual-energy radiograph absorptiometry. RESULTS:
      After surgery, we observed significant improvements in respiratory function
      (FEV1, + 18.8% [p < 0.01]; residual volume [RV], -29.6% [p < 0.001]; diffusing
      capacity of the lung for carbon monoxide [Dlco], + 21.6% [p < 0.01]) nutritional
      parameters (fat-free mass, + 6.0% [p < 0.01]), levels of bone-related hormones
      (free-testosterone, + 20.5% [p < 0.01]; parathormone, -11.2% [p < 0.01]), bone
      turnover markers (osteocalcin, -12.7% [p < 0.05]; bone-alkaline-phosphatase, 
      14.0% [p < 0.05]; beta-crosslaps, -33.6% [p < 0.001]), BMD (lumbar, + 8.8% [p <
      0.01]; femoral, + 5.5% [p < 0.01]), and T-score (lumbar, + 21.0% [p < 0.01];
      femoral, + 12.4% [p < 0.01]) with reduction in osteoporosis rate (50 to 25%).
      Nineteen patients who had undergone surgery were able to discontinue treatment
      with oral steroids. These subjects showed a more significant improvement in BMD
      (lumbar, + 9.6%; femoral, + 6.8%; p < 0.001) and T-score (lumbar, + 27.3%;
      femoral, + 14.3%; p < 0.001). The remaining 21 patients who had undergone surgery
      experienced significant improvement compared to respiratory rehabilitation
      subjects despite continued therapy with oral steroids (BMD: lumbar, + 4.5% vs 
      0.7%, respectively [p < 0.01]; femoral, + 2.7% vs -1.1%, respectively [p < 0.05];
      T-score: lumbar, + 14 vs -2.1, respectively [p < 0.01]; femoral, + 7.4 vs -2.7,
      respectively [p < 0.01]). The increase in lumbar BMD was correlated with the
      surgical reduction of RV (p = 0.02) and with the increase in Dlco (p = 0.01) and
      fat-free mass (p = 0.01). CONCLUSIONS: Lung volume reduction surgery
      significantly improves BMD compared to respiratory rehabilitation therapy, even
      in patients requiring oral steroids. The increase in BMD correlates with RV,
      Dlco, and fat-free mass, suggesting that the restoration of respiratory dynamics,
      gas exchange, and nutritional status induces improvement in bone metabolism and
      mineral content.

PMID- 15947309
TI  - Relation between neurocognitive impairment, embolic load, and cerebrovascular
      reactivity following on- and off-pump coronary artery bypass grafting.
AB  - OBJECTIVES: To evaluate the effect of on-pump and off-pump coronary artery bypass
      grafting (CABG) on postoperative cognitive impairment and cerebrovascular
      reactivity, with attention for the perioperative high-intensity transient signals
      (HITS). DESIGN: A prospective comparative study. SETTING: Urban university
      hospital. PATIENTS: Candidates for cardiac surgery. METHODS: Measurement of HITS
      as a reflection of embolic load was performed in 50 patients (on-pump CABG, n =
      32; off-pump CABG, n = 18). To measure cognitively induced cerebrovascular
      reactivity, cerebral blood flow velocity (BFV) was measured preoperatively in 66
      patients, early postoperatively (after 6 days) in 63 patients, and late
      postoperatively (after 6 months) in 44 patients during five cognitive tasks. In
      the same session, seven standardized neuropsychological tests were administered.
      RESULTS: A higher embolic load was found in the on-pump group (p < 0.01). In the
      on-pump group, aortic cannulation was the most important HITS-prone surgical
      maneuver. Repeated-measures multivariate analysis of variance (using surgical
      technique as between-subjects factor and significant differences between both
      groups as covariates) on the group data revealed no significant differences in
      neuropsychological performance and BFV immediately after surgery or at 6 months
      after surgery, compared with preoperative performance. No main effect of surgery
      was found for neuropsychological performance and BFV. No significant correlations
      were found between the number of HITS and the degree of postoperative
      neuropsychological impairment. Individual comparisons revealed that 60% (59.4% in
      the on-pump group; 61.1% in the off-pump group) of the patients undergoing CABG
      showed evidence of cognitive impairment soon after surgery. In 24.2%, the
      cognitive sequelae persisted at 6 months follow-up (31.8% in the on-pump group;
      9.1% in the off-pump group). The cognitive impairment index (sum of impaired
      neuropsychological tests) showed a significant difference after 6 months between
      both surgery groups with fewer neurocognitive tests that remained impaired in the
      off-pump group. CONCLUSIONS: In off-pump surgery, significantly fewer HITS were
      observed. On an individual level, more favorable results in neuropsychological
      test performance were demonstrated in the off-pump group after 6 months. The
      number of HITS showed no correlation with degrees of early and late postoperative
      neuropsychological impairment.

PMID- 15947310
TI  - Smoking and timing of cessation: impact on pulmonary complications after
      thoracotomy.
AB  - STUDY OBJECTIVE: The benefit of smoking cessation just prior to surgery in
      preventing postoperative pulmonary complications has not been proven. Some
      studies actually show a paradoxical increase in complications in those quitting
      smoking only a few weeks or days prior to surgery. We studied the effect of
      smoking and the timing of smoking cessation on postoperative pulmonary
      complications in patients undergoing thoracotomy. DESIGN AND SETTING: Prospective
      study conducted in a tertiary care cancer center in 300 consecutive patients with
      primary lung cancer or metastatic cancer to the lung who were undergoing
      anatomical lung resection. RESULTS: The groups studied were nonsmokers (21%),
      past quitters of > 2 months duration (62%), recent quitters of < 2 months
      duration (13%), and ongoing smokers (4%). Overall pulmonary complications
      occurred in 8%, 19%, 23%, and 23% of these groups, respectively, with a
      significant difference between nonsmokers and all smokers (p = 0.03) but no
      difference among the subgroups of smokers (p = 0.76). The risk of pneumonia was
      significantly lower in nonsmokers (3%) compared to all smokers (average, 11%; p <
      0.05), with no difference detected among subgroups of smokers (p = 0.17).
      Comparing recent quitters and ongoing smokers, no differences in pulmonary
      complications or pneumonia were found (p = 0.67). Independent risk factors for
      pulmonary complications were a lower diffusing capacity of the lung for carbon
      monoxide (Dlco) [odds ratio [ OR] per 10% decrement, 1.41; 95% confidence
      interval [ CI], 1.17 to 1.70; p = 0.01) and primary lung cancer rather than
      metastatic disease (OR, 3.94; 95% CI, 1.34 to 11.59; p = 0.003). Among smokers, a
      lower Dlco percent predicted (OR per 10% decrement, 1.42; 95% CI, 1.16 to 1.75; p
      = 0.008) and a smoking history of > 60 pack-years (OR, 2.54; 95% CI, 1.28 to
      5.04; p = 0.0008) were independently associated with overall pulmonary
      complications. CONCLUSIONS: In patients undergoing thoracotomy for primary or
      secondary lung tumors, there is no evidence of a paradoxical increase in
      pulmonary complications among those who quit smoking within 2 months of
      undergoing surgery. Smoking cessation can safely be encouraged prior to surgery.

PMID- 15947311
TI  - A comparison of gender differences in health-related quality of life in acute and
      chronic coughers.
AB  - STUDY OBJECTIVES: To determine whether the health-related quality of life (HRQOL)
      of women and men is adversely affected by acute cough (AC), affected differently
      by AC, or affected differently by AC and chronic cough (CC). DESIGN: Analysis of
      consecutively and prospectively collected AC data from two time periods, and
      previously prospectively and consecutively collected CC data that had not been
      previously analyzed. When no differences were found in the two cohorts of acute
      coughers, as was the case in the greatest majority of comparisons, the two
      samples were pooled, treated as one sample of acute coughers, and compared with
      chronic coughers. SETTINGS: Primary care and cough clinics in an academic,
      tertiary care medical center. PARTICIPANTS: Subjects prospectively seeking
      medical attention complaining of AC for < 3 weeks and CC for at least 8 weeks.
      MEASUREMENT: All subjects completed the cough-specific quality-of-life
      questionnaire (CQLQ) prior to contact with a physician and medical intervention.
      RESULTS: Of 62 acute coughers, 32 were women and 30 were men (p = 0.25). Total
      CQLQ scores for women were 59.9, and for men they were 59.2. (There was no
      difference in total CQLQ scores in the two cohorts of acute coughers.) The mean
      (+/- SD) combined total CQLQ score of women and men of 59.57 +/- 10.4 was higher
      (t90 = 11.39; p < 0.0001) than the score in an historical control group of women
      and men who were not complaining of cough (35.06 +/- 8.40). In acute coughers,
      there were no gender differences in the total or six subscale scores when the two
      cohorts were considered separately or combined. Of 172 chronic coughers, 116 were
      women and 56 were men (p < 0.0001). Women with CC rated themselves significantly
      higher than did women with AC on the total CQLQ and on five of the six subscales.
      Women with AC did not rate themselves higher on any of the CQLQ subscales. Total
      CQLQ scores for men with AC and CC were similar. Men with CC, compared with men
      with AC, scored significantly higher in two of six subscales (and significantly
      lower in one subscale) and scored similarly in three subscales. CONCLUSIONS: AC,
      like CC, adversely affected the HRQOL of women and men. Unlike CC, AC did not
      adversely affect the HRQOL of women more than men. The HRQOL of women is more
      adversely affected than the HRQOL of men, the longer a cough lasts.

PMID- 15947312
TI  - A prospective feasibility study of bronchial thermoplasty in the human airway.
AB  - BACKGROUND: Bronchial thermoplasty is a novel procedure being developed as a
      potential treatment for asthma. Experience with animal studies has enabled
      development of appropriate reliable equipment, definition of therapeutic
      parameters, and descriptions of tissue effects of treatment. STUDY OBJECTIVES:
      This study was undertaken to assess the feasibility and general safety of the
      application of bronchial thermoplasty in the human airway, and to determine if
      the reduction in airway smooth muscle seen in animal studies could be replicated.
      DESIGN: A prospective study. SETTING: Academic thoracic surgery center.
      PARTICIPANTS: Nine patients scheduled to undergo lung resection for suspected or
      proven lung cancer. INTERVENTIONS: Bronchial thermoplasty was performed during
      routine preoperative bronchoscopy up to 3 weeks prior to prescheduled lung
      resection. Treatment was limited to areas of the segmental bronchi within the
      lobe that was to be removed. Treated airways were inspected via bronchoscopy at
      the time of thoracotomy, and were examined histologically following surgical
      resection. RESULTS: There were no adverse clinical effects of the procedure,
      including no new symptoms and no unscheduled visits for medical care. Treated
      sites exhibited slight redness and edema of the mucosa within 2 weeks of
      treatment, and appeared normal at later time points. There was narrowing
      (visually estimated at 25 to 50%) in four airways in two subjects examined at 5
      days and 13 days after treatment, with excess mucus in two of these airways.
      There was no bronchoscopic evidence of scarring in any of the airways examined.
      Histologic examination showed a reduction in airway smooth muscle, and the extent
      of the treatment effect was confined to the airway wall and the immediate
      peribronchial region. CONCLUSION: Application of bronchial thermoplasty to the
      human airway appears to be well tolerated. Treatment resulted in significant
      reduction of smooth muscle mass in the airways. Bronchial thermoplasty may
      provide therapeutic benefit in disease states such as asthma.

PMID- 15947313
TI  - Cryosurgery for malignant endobronchial tumors: analysis of outcome.
AB  - STUDY OBJECTIVES: More than 80% of patients with lung cancer are unsuitable for
      curative surgical treatment. Palliative relief of symptoms, often caused by
      airway obstruction, is very important. Endobronchial cryosurgery is used for
      destruction of intraluminal tumors. This study analyzes the effects of
      cryosurgery on patients with obstructive endobronchial carcinoma. DESIGN:
      Retrospective analysis of data extracted from a prospective computerized
      database. SETTING: Tertiary referral thoracic surgical center. PATIENTS: Data of
      the 172 patients who underwent at least two sessions of endobronchial cryosurgery
      (group A) were compared with 157 patients who underwent one session of
      cryosurgery (group B) for malignant primary or metastatic obstructive lung
      carcinoma over a 5-year period. INTERVENTION: Endobronchial cryosurgery is
      performed under general anesthesia. A nitrous oxide cryoprobe is inserted through
      a rigid bronchoscope. The probe achieves a temperature of - 70 degrees C at its
      tip and is applied to the tumor for two 3-min periods. Statistical analysis
      assessed the effects of cryosurgery on symptoms, lung function, Karnofsky
      performance score, and survival. RESULTS: Symptoms of dyspnea, cough, and
      hemoptysis were significantly reduced in both groups after cryosurgery (p <
      0.001), although group A benefited more than group B. Lung function test results
      improved significantly in group A. The mean Karnofsky performance score (+/- SD)
      increased from 67 +/- 9 to 74 +/- 10 (group A) and from 67 +/- 10 to 73 +/- 11
      (group B). The mean survival was 15 months (median, 11 months) for group A and
      8.3 months (median, 6 months) for group B (p = 0.006). Univariate regression
      analysis showed that no particular patient or tumor characteristic was associated
      with reduction of symptoms. Patients who had cryosurgery and external beam
      radiotherapy showed longer survival (p < 0.01). Females and patients with stage
      IIIa and IIIb tumors achieved significantly improved Karnofsky scores (p < 0.02).
      Female sex was also a factor for increase in FEV at 1 min (p = 0.003) and FVC (p
      < 0.001). CONCLUSIONS: Cryosurgery is a safe method for palliation of
      endobronchial malignancies causing airway obstruction. Statistical analysis
      showed improvement of dyspnea, cough, and hemoptysis. Cryosurgery can be
      considered in patients with inoperable obstructive endobronchial carcinoma.

PMID- 15947314
TI  - Transbronchial needle aspirates: comparison of two preparation methods.
AB  - STUDY OBJECTIVES: Transbronchial needle aspiration has evolved as a key
      bronchoscopic sampling method. Specimen handling and preparation are underrated
      yet crucial aspects of the technique. This study was designed to identify which
      of two widely practiced sample preparation methods has a higher yield. DESIGN:
      Prospective comparison of two diagnostic methods. SETTING: Tertiary academic
      hospital. PATIENTS: Consecutive patients undergoing transbronchial needle
      aspiration. INTERVENTIONS: Transbronchial aspirates were obtained pairwise. One
      specimen was placed directly onto a slide and smears were prepared on site (ie,
      the direct technique), and the other specimen was deposited into a vial
      containing 95% alcohol and further prepared in the laboratory (ie, the fluid
      technique). In total, 282 pairs of samples were aspirated from 145 target sites
      (paratracheal, 10 sites; tracheobronchial, 101 sites; hilar, 17 sites;
      endobronchial or peripheral, 17 sites). MEASUREMENTS AND RESULTS: The measured
      outcome was the presence of diagnostic material at the final laboratory
      assessment. At least one diagnostic aspirate was obtained in 66% of 86
      investigated patients (small cell lung cancer, 18 patients; non-small cell lung
      cancer, 47 patients; other diagnoses, 21 patients). The direct technique had a
      better yield overall than the fluid technique (positive aspirates, 36.2% vs
      12.4%, respectively; p < 0.01), as well as after stratification for tumor type
      and for anatomic site. CONCLUSION: The direct technique is superior to the fluid
      technique for the preparation of transbronchial needle aspirates.

PMID- 15947315
TI  - Histopathologic pattern and clinical features of rheumatoid arthritis-associated
      interstitial lung disease.
AB  - STUDY OBJECTIVES: To investigate the histopathologic pattern and clinical
      features of patients with rheumatoid arthritis (RA)-associated interstitial lung
      disease (ILD) according to the American Thoracic Society (ATS)/European
      Respiratory Society consensus classification of idiopathic interstitial
      pneumonia. DESIGN: Retrospective review. SETTING: Two thousand-bed, university
      affiliated, tertiary referral center. PATIENTS: Eighteen patients with RA who
      underwent surgical lung biopsy (SLBx) for suspected ILD. METHOD: SLBx specimens
      were reviewed and reclassified by three lung pathologists according to the
      ATS/European Respiratory Society classification. Clinical features and follow-up
      courses for the usual interstitial pneumonia (UIP) pattern and the nonspecific
      interstitial pneumonia (NSIP) pattern were compared. RESULTS: The histopathologic
      patterns were diverse: 10 patients with the UIP pattern, 6 patients with the NSIP
      pattern, and 2 patients with inflammatory airway disease with the organizing
      pneumonia pattern. RA preceded ILD in the majority of patients (n = 12). In three
      patients, ILD preceded RA; in three patients, both conditions were diagnosed
      simultaneously. The majority (n = 13) of patients had a restrictive defect with
      or without low diffusion capacity of the lung for carbon monoxide (D(LCO)) on
      pulmonary function testing; 2 patients had only low (D(LCO)). The UIP and NSIP
      groups were significantly different in their male/female ratios (8/2 vs 0/6,
      respectively; p = 0.007) and smoking history (current/former or nonsmokers, 8/2
      vs 0/6; p = 0.007). Many of the patients with the UIP pattern had typical high
      resolution CT features of UIP. Five patients with the UIP pattern died, whereas
      no deaths occurred among patients with the NSIP pattern during median follow-up
      durations of 4.2 years and 3.7 years, respectively. CONCLUSIONS: The
      histopathologic type of RA-ILD was diverse; in our study population, the UIP
      pattern seemed to be more prevalent than the NSIP pattern.

PMID- 15947316
TI  - Quadriceps weakness is related to exercise capacity in idiopathic pulmonary
      fibrosis.
AB  - STUDY OBJECTIVE: In COPD, it has been shown that peripheral muscle dysfunction is
      a factor determining exercise intolerance. We examined the hypothesis that
      exercise capacity of patients with idiopathic pulmonary fibrosis (IPF) is, at
      least in part, determined by peripheral muscle dysfunction. METHODS: Maximum
      oxygen uptake (V(O2)max) was evaluated in 41 consecutive patients with IPF, along
      with potential determinants of exercise capacity, both in the lungs and in the
      peripheral muscles. RESULTS: Patients had reduced V(O2)max (893 +/- 314 mL, 46.0%
      predicted) and reduced quadriceps force (QF) [65% predicted]. Significant
      correlates of V(O2)max reduction were vital capacity (VC) [r = 0.79], total lung
      capacity (r = 0.64), diffusion capacity (r = 0.64), QF (r = 0.62), maximum
      expiratory pressure (r = 0.48), and Pa(O2) at rest (r = 0.33). In stepwise
      multiple regression analysis, VC and QF were independent predictors of V(O2)max.
      Furthermore, in subgroup analysis, QF was a significant contributing factor for
      V(O2)max in patients who discontinued exercise because of dyspnea and/or leg
      fatigue. CONCLUSIONS: We conclude that QF is a predictor of exercise capacity in
      IPF. Measures that improve muscle function might improve exercise tolerance.

PMID- 15947317
TI  - Familial idiopathic pulmonary fibrosis: clinical features and outcome.
AB  - STUDY OBJECTIVES: Familial idiopathic pulmonary fibrosis (FIPF) has been defined
      as idiopathic pulmonary fibrosis (IPF) occurring in two or more members of a
      family. The clinical course of FIPF has not been fully defined. Accordingly, the
      current study was undertaken to establish clinical, radiologic, and histologic
      features, and survival in a consecutive series of patients with FIPF. DESIGN:
      Retrospective analysis of clinical, radiologic, and pathologic data from a
      consecutive series of patients with FIPF who were seen at Mayo Medical Center.
      Survival in patients with FIPF was contrasted to that of previously characterized
      patients with nonfamilial IPF who were evaluated at our institution. SETTING:
      Tertiary referral medical center. PATIENTS: We screened 47 patients and family
      members with FIPF from 15 families who were identified between the years 1992 and
      2002. We further analyzed the subgroup of FIPF patients that was composed of 27
      patients from 15 families in whom the complete clinical course was monitored at
      our institution. MEASUREMENTS: All patients exhibited clinical features that were
      compatible with IPF and either compatible high-resolution CT (HRCT) scan findings
      or histologic evidence of usual interstitial pneumonia. Clinical data, including
      symptoms, physical findings, HRCT scan findings, lung function test results,
      biopsy results, and survival were abstracted from the clinical records. RESULTS:
      Compared to patients with nonfamilial IPF, patients with FIPF did not demonstrate
      any notable differences in clinical, radiologic, or pathologic features. We
      observed that the total number of affected members in a family with FIPF was a
      significant risk factor for earlier mortality (p = 0.0157; hazard ratio, 1.434).
      Overall, however, patients with FIPF had a statistically similar outcome to those
      patients with nonfamilial IPF. CONCLUSIONS: Although uncommon, FIPF represents a
      distinct syndrome, which has clinical features and patient survival rates that
      are similar to those of nonfamilial IPF.

PMID- 15947318
TI  - Improving outcomes in heart failure in the community: long-term survival benefit
      of a disease-management program.
AB  - OBJECTIVES: The purpose of our current study was to determine whether our disease
      management model was associated with long-term survival benefits. A secondary
      objective was to determine whether program involvement was associated with
      medication maintenance and reduced hospitalization over time compared to usual
      care management of heart failure. DESIGN: A retrospective chart review was
      conducted in patients who had been hospitalized for congestive heart failure
      between April 1999 and March 31, 2000, and had been discharged from the hospital
      for follow-up in the Heart Failure Clinic vs usual care. SETTING: An integrated
      health-care center serving a tristate area. PATIENTS: Patients (n = 101) were
      followed up for 4 years after their index hospitalization for congestive heart
      failure. MEASUREMENTS AND RESULTS: The patients followed up in the Heart Failure
      Clinic comprised group 1 (n = 38), and the patients receiving usual care made up
      group 2 (n = 63). The mean (+/- SD) age of the patients in group 1 was 68 +/- 16
      years compared to 76 +/- 11 years for the patients in group 2 (p = 0.002). The
      patients in group 1 were more likely to have renal failure (p = 0.035), a lower
      left ventricular ejection fraction (p = 0.005), and hypotension at baseline (p =
      0.002). At year 2, more patients in group 1 were maintained by therapy with
      angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers
      (ARBs) [p = 0.036]. The survival rate over 4 years was better for group 1.
      Univariate Cox proportional hazard ratios revealed that age, not receiving ACEIs
      or ARBs, and renal disease or cancer at baseline were associated with mortality.
      When controlling for these variables in a multivariate Cox proportional hazards
      ratio model, survival differences between groups remained significant (p =
      0.021). Subjects in group 2 were 2.4 times more likely to die over the 4-year
      period than those in group 1. CONCLUSIONS: Our study demonstrated that, after
      controlling for baseline variables, patients participating in a heart failure
      clinic enjoyed improved survival.

PMID- 15947319
TI  - Warfarin maintenance dosing patterns in clinical practice: implications for safer
      anticoagulation in the elderly population.
AB  - BACKGROUND: The use of anticoagulant therapy is expanding among the elderly
      population, in part because of the increasing prevalence of atrial fibrillation.
      Published data describing the warfarin maintenance dose requirements for this age
      group are limited. Because warfarin therapy is often initiated in the outpatient
      setting where significant barriers to daily monitoring exist for this patient
      population, a better understanding of the factors that predict lower dose
      requirements may reduce the risk of unanticipated over-anticoagulation and
      hemorrhage. OBJECTIVE: To define the effects of age and gender on the warfarin
      maintenance dose among ambulatory adult patients with an international normalized
      ratio target between 2.0 and 3.0. DESIGN: Prospective cohort study and
      retrospective cohort secondary data source. SETTING: One hundred one community
      based physician practices with dedicated warfarin management systems and an
      academic medical center anticoagulation clinic. PATIENTS: A total of 4,616
      patients comprised the prospective cohort, and 7,586 patients comprised the
      retrospective cohort. Of the 12,202 patients, 2,359 were > or = 80 years of age.
      MEASUREMENTS: Median weekly and daily maintenance warfarin dose. RESULTS: The
      warfarin dose was inversely related to age and was strongly associated with
      gender. The median weekly dose ranged from 45 mg (6.4 mg/d) for men who were < 50
      years of age to 22 mg (3.1 mg/d) for women > or = 80 years of age. The weekly
      dose declined by 0.4 mg/yr (95% confidence interval [CI], 0.37 to 0.44; p <
      0.001) and women required 4.5 mg less per week than men (95% CI, 3.8 to 5.3; p <
      0.001). Among patients who were > 70 years of age, the often-suggested initiation
      dose of 5 mg/d will be excessive for 82% of women and 65% of men. CONCLUSIONS:
      Warfarin dose requirements decrease greatly with age. Older women require the
      lowest warfarin doses. These observations suggest that, when warfarin is being
      initiated, the commonly employed empiric starting dose of 5 mg/d will lead to
      over-anticoagulation for the majority of patients in the geriatric age group;
      lower initiation and maintenance doses should be considered for the elderly.

PMID- 15947320
TI  - Acute electrophysiologic effects of inhaled salbutamol in humans.
AB  - STUDY OBJECTIVES: Although inhaled beta2-agonists are in widespread use, several
      reports question their potential arrhythmogenic effects. The purpose of this
      study was to evaluate the cardiac electrophysiologic effects of a single, regular
      dose of an inhaled beta2-agonist in humans. DESIGN: Prospective study. SETTING:
      Tertiary referral center. PATIENTS: Six patients with bronchial asthma and 12
      patients with mild COPD. INTERVENTIONS: All patients underwent an
      electrophysiologic study before and after the administration of salbutamol
      solution (5 mg in a single dose). MEASUREMENTS AND RESULTS: Sinus cycle length,
      sinus node recovery time (SNRT), interval from the earliest reproducible rapid
      deflection of the atrial electrogram in the His bundle recording to the onset of
      the His deflection (AH), interval from the His deflection to the onset of
      ventricular depolarization (HV), Wenckebach cycle length (WCL), atrial effective
      refractory period (AERP), and ventricular effective refractory period (VERP) were
      evaluated just before and 30 min after the scheduled intervention. Salbutamol, a
      selective beta2-agonist, administered by nebulizer had significant
      electrophysiologic effects on the atrium, nodes, and ventricle. The AH length
      decreased from 86.1 +/- 19.5 ms at baseline to 78.8 +/- 18.4 ms (p < 0.001), and
      the WCL decreased from 354.4 +/- 44.2 to 336.6 +/- 41.7 ms (p = 0.001).
      Salbutamol significantly decreased the AERP and VERP too while leaving the HV
      unchanged. Additionally, inhaled salbutamol increased heart rate (from 75.5 +/-
      12.8 beats/min at baseline to 93.1 +/- 16 beats/min, p < 0.001) and shortened the
      SNRT (from 1,073.5 +/- 178.7 to 925.2 +/- 204.9 ms, p = 0.001). CONCLUSION:
      Inhaled salbutamol results in significant changes of cardiac electrophysiologic
      properties. Salbutamol enhances atrioventricular (AV) nodal conduction and
      decreases AV nodal, atrial, and ventricular refractoriness in addition to its
      positive chronotropic effects. These alterations could contribute to the
      generation of spontaneous arrhythmias.

PMID- 15947321
TI  - Zinc chloride (smoke bomb) inhalation lung injury: clinical presentations, high
      resolution CT findings, and pulmonary function test results.
AB  - STUDY OBJECTIVES: Zinc chloride smoke inhalation injury (ZCSII) is uncommon and
      has been rarely described in previous studies. We hypothesized that structural
      changes of the lung might correlate with pulmonary function. To answer this
      question, we correlated findings from high-resolution CT (HRCT) scan and the
      results of pulmonary function tests (PFTs) in patients with ZCSII. DESIGN:
      Retrospective cohort study. SETTING: University hospital. PATIENTS: Twenty
      patients who had been hospitalized with ZCSII-related conditions. MEASUREMENTS:
      The study included HRCT scan scores (0 to 100), static and dynamic lung volumes,
      and diffusing capacity of the lung for carbon monoxide (D(LCO)). RESULTS: HRCT
      scans and PFTs were performed initially after injury (range, 3 to 21 days) in all
      patients and during the follow-up period (range, 27 to 66 days) in 10 patients.
      The predominant CT scan findings were patchy or diffuse ground-glass opacities
      with or without consolidation. The majority of patients showed a significant
      reduction of FVC, FEV1, total lung capacity, and D(LCO), but normal FEV1/FVC
      ratio values. Changes of functional parameters correlated well with HRCT scan
      scores. Substantial improvements in CT scan abnormalities and pulmonary function
      were observed at follow-up. CONCLUSIONS: The majority of our patients with ZCSII
      presented with a predominant parenchymal injury of the lung that was consistent
      with a restrictive type of functional impairment and a reduction in Dlco rather
      than with obstructive disease. Our results suggest that HRCT scanning and
      pulmonary function testing may reliably predict the severity of ZCSII.

PMID- 15947322
TI  - Recovery of potential pathogens and interfering bacteria in the nasopharynx of
      smokers and nonsmokers.
AB  - BACKGROUND: Active smoking and passive exposure to cigarette smoke are associated
      with colonization by some potentially pathogenic species of bacteria and an
      increased risk of respiratory tract infection in both adults and children. In an
      attempt to explain these observations, this study compared the frequency of
      isolation of potential pathogens, and aerobic and anaerobic bacteria that possess
      interfering capabilities (ie, interfering with the in vitro growth of potential
      pathogens) in the nasopharynx of smokers to their recovery in nonsmokers.
      METHODS: Nasopharyngeal specimens for cultures were taken from 20 smokers and 20
      nonsmokers. Potential pathogens, and aerobic and anaerobic bacteria with
      interfering capabilities against these organisms were identified. RESULTS:
      Fourteen potential pathogens (0.7 per patient) were isolated from nasopharyngeal
      cultures obtained from 11 of the 20 smokers, and 4 (0.2 per patient) were
      recovered from 3 of the 20 nonsmokers (p < 0.01). In vitro bacterial interference
      between two aerobic (alpha-hemolytic and nonhemolytic streptococci) and two
      anaerobic species (Prevotella and Peptostreptococcus species), and four potential
      pathogens (Streptococcus pneumoniae, Haemophilus influenzae [non-type b],
      Moraxella catarrhalis, and Streptococcus pyogenes) was observed. Bacterial
      interference was noted in 61 instances against the four potential pathogens by 22
      normal flora isolates that were recovered from the group of smokers, and in 155
      instances by 50 isolates from the group of nonsmokers (p < 0.01). CONCLUSIONS:
      These findings illustrate for the first time that the nasopharyngeal flora of
      smokers contains fewer aerobic and anaerobic organisms with interfering
      capabilities and more potential pathogens compared with those of nonsmokers.

PMID- 15947323
TI  - Long-term effects of nasal continuous positive airway pressure therapy on
      cardiovascular outcomes in sleep apnea syndrome.
AB  - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been associated with
      increased morbidity and mortality, principally from cardiovascular disease, but
      the impact of nasal continuous positive airway pressure (CPAP) therapy is
      unclear. METHODS: We performed a long-term follow-up study of 168 patients with
      OSAS who had begun receiving CPAP therapy at least 5 years previously, most of
      whom had been prospectively followed up, having been the subject of an earlier
      report on cardiovascular risk factors in OSAS patients. The average follow-up
      period was 7.5 years. We compared the cardiovascular outcomes of those patients
      who were intolerant of CPAP (untreated group, 61 patients) with those continuing
      CPAP therapy (107 patients). RESULTS: CPAP-treated patients had a higher median
      apnea-hypopnea index score than the untreated group (48.3 [interquartile range
      (IQR), 33.6 to 66.4] vs 36.7 [IQR, 27.4 to 55], respectively; p = 0.02), but age,
      body mass index, and time since diagnosis were similar. Deaths from
      cardiovascular disease were more common in the untreated group than in the CPAP
      treated group during follow-up (14.8% vs 1.9%, respectively; p = 0.009 [log rank
      test]), but no significant differences were found in the development of new cases
      of hypertension, cardiac disorder, or stroke. Total cardiovascular events (ie,
      death and new cardiovascular disease combined) were more common in the untreated
      group than in the CPAP-treated group (31% vs 18%, respectively; p < 0.05).
      CONCLUSIONS: The data support a protective effect of CPAP therapy against death
      from cardiovascular disease in patients with OSAS.

PMID- 15947324
TI  - Treatment adherence and outcomes in flexible vs standard continuous positive
      airway pressure therapy.
AB  - STUDY OBJECTIVES: To compare adherence and clinical outcomes between flexible
      positive airway pressure (PAP) [C-Flex; Respironics; Murraysville, PA] and
      standard PAP therapy (ie, continuous positive airway pressure [CPAP]). DESIGN AND
      SETTING: A controlled clinical trial of CPAP therapy vs therapy using the C-Flex
      device in participants with moderate-to-severe obstructive sleep apnea.
      Participants were recruited from and followed up through an academic sleep
      disorders center. PARTICIPANTS: Eighty-nine participants were recruited into the
      study after they had undergone complete in-laboratory polysomnography and before
      initiating therapy. Participants received either therapy with CPAP (n = 41) or
      with the C-Flex device (n = 48), depending on the available treatment at the time
      of recruitment, with those recruited earlier receiving CPAP therapy and those
      recruited later receiving therapy with the C-Flex device. Follow-up assessments
      were conducted at 3 months. MEASUREMENTS AND RESULTS: The groups were similar
      demographically. The mean (+/- SD) treatment adherence over the 3-month follow-up
      period was higher in the C-Flex group compared to the CPAP group (weeks 2 to 4,
      4.2 +/- 2.4 vs 3.5 +/- 2.8, respectively; weeks 9 to 12, 4.8 +/- 2.4 vs 3.1 +/-
      2.8, respectively). Clinical outcomes and attitudes toward treatment (self
      efficacy) were also measured. Change in subjective sleepiness and functional
      outcomes associated with sleep did not improve more in one group over the other.
      Self-efficacy showed a trend toward being higher at the follow-up in those
      patients who had been treated with the C-Flex device compared to CPAP treatment.
      CONCLUSIONS: Therapy with the C-Flex device may improve overall adherence over 3
      months compared to standard therapy with CPAP. Clinical outcomes do not improve
      consistently, but C-Flex users may be more confident about their ability to
      adhere to treatment. Randomized clinical trials are needed to replicate these
      findings.

PMID- 15947325
TI  - Eotaxin-3 and interleukin-5 pleural fluid levels are associated with pleural
      fluid eosinophilia in post-coronary artery bypass grafting pleural effusions.
AB  - OBJECTIVES: The primary aim of this study was to examine the association between
      pleural fluid (PF) eosinophilia, and the PF and serum levels of interleukin (IL)
      5, eotaxin-2, eotaxin-3, and vascular cell adhesion molecule (VCAM)-1 in patients
      with post-coronary artery bypass grafting (CABG) pleural effusions. DESIGN: A
      prospective observational study. SETTING: A tertiary teaching hospital. PATIENTS
      AND METHODS: Thirty-eight patients with post-CABG pleural effusions were
      recruited into the study. An effusion that contained at least 10% eosinophils was
      called "eosinophilic." The PF and serum levels of the cytokines and VCAM-1 were
      measured using an enzyme-linked immunosorbent assay. RESULTS: (1) The number of
      PF eosinophils significantly correlated with the number of blood eosinophils. (2)
      PF IL-5 levels were significantly higher than the corresponding serum levels, and
      there was a significant correlation between the PF and serum IL-5 levels. PF IL-5
      levels significantly correlated with the PF eosinophil count, and serum IL-5
      levels significantly correlated with the number of blood eosinophils. (3) PF
      eotaxin-3 levels were significantly higher than serum levels, and PF eotaxin-3
      levels significantly correlated with the PF eosinophil count. (4) PF VCAM-1
      levels were significantly lower than the corresponding serum levels, and PF VCAM
      1 levels were significantly higher in eosinophilic pleural effusions (EPEs) than
      in non-EPEs. CONCLUSION: In patients with post-CABG pleural effusions, IL-5 and
      eotaxin-3 are produced preferentially in the pleural cavity, and they are
      strongly associated with PF eosinophilia.

PMID- 15947326
TI  - Thoracentesis in patients with hematologic malignancy: yield and safety.
AB  - BACKGROUND: Pleural effusions occur in patients with hematologic malignancies,
      particularly during periods of hospitalization. Thoracentesis is often performed
      to diagnose infection and to exclude the presence of complicated parapneumonic
      effusions. The efficacy and safety of thoracentesis in this setting has not been
      well-studied. DESIGN: Retrospective chart review of hospitalized patients with
      hematologic malignancies undergoing thoracentesis. The aim of this study was to
      assess the role of thoracentesis in establishing a diagnosis of infection in this
      population and to determine the risk of complications. RESULTS: A total of 100
      thoracentesis findings were analyzed in patients with lymphoma (52 patients) and
      leukemia (27 patients), and in patients who had undergone bone marrow or stem
      cell transplantation (21 patients). The indication for performing thoracentesis
      was to exclude infection in 69% of cases. Fever was present in 59% of the
      patients, and a concomitant lung parenchymal abnormality was present in 69% of
      cases. Effusions were moderate to large in size (87% of cases), and were both
      bilateral (62%) and unilateral (38%). Exudates were documented in 83%of the
      cases. A specific diagnosis was found in 21 patients and was more frequently
      established in those with lymphoma (31%) compared to the other groups of
      patients. Diagnoses found included malignancy in 14 cases, chylous effusions in 6
      cases, and infection in 1 case. The one patient in whom empyema was found
      required drainage. The criteria for a parapneumonic effusion were not found in
      any other patients. The complication rate of 9% (pneumothorax, seven patients;
      hemothorax, two patients) was comparable to that in other populations of
      patients. CONCLUSIONS: Despite a high propensity for developing pulmonary
      infections, hospitalized patients with hematologic malignancies rarely developed
      complex parapneumonic effusions. The etiology of many of the effusions that
      occurred in this setting was unclear.

PMID- 15947327
TI  - Endoscopic removal of metallic airway stents.
AB  - BACKGROUND: Complications of metallic airway stents include granulation tissue
      formation, fracture of struts, migration, and mucous plugging. When these
      complications result in airway injury or obstruction, it may become necessary to
      remove the stent. There have been few reports detailing techniques and
      complications associated with endoscopic removal of metallic airway stents. We
      report our experience with endoscopic removal of 30 such stents over a 3-year
      period. METHODS: We conducted a retrospective review of 25 patients who underwent
      endoscopic stent removal from March 2001 to April 2004. The patients ranged in
      age from 17 to 80 years (mean, 56.3 years). There were 10 male and 15 female
      patients. The stents had been placed for nonmalignant disease in 20 patients
      (80%) and malignant disease in 5 patients (20%). All procedures were done under
      general anesthesia with a rigid bronchoscope. Special attention was focused on
      the technique of stent removal and postoperative complications. RESULTS: Thirty
      metallic airway stents were successfully removed from 25 consecutive patients
      over a 3-year period. The basic method of removal involved the steady application
      of traction to the stent with alligator forceps. In all cases, an instrument such
      as the barrel of the rigid bronchoscope or a Jackson dilator was employed to help
      separate the stent from the airway wall before removal was attempted. In some
      instances, the airway wall was pretreated with thermal energy prior to stent
      removal. Complications were as follows: retained stent pieces (n = 7), mucosal
      tear with bleeding (n = 4), re-obstruction requiring temporary silicone stent
      placement (n = 14), need for postoperative mechanical ventilation (n = 6), and
      tension pneumothorax (n = 1). CONCLUSIONS: Although metallic stents may be safely
      removed endoscopically, complications are common and must be anticipated. Other
      investigators have described airway obstruction and death as a result of
      attempted stent removal. Placement and removal of metallic airway stents should
      only be performed at centers that are prepared to deal with the potentially life
      threatening complications.

PMID- 15947328
TI  - Bronchoscopy-guided topical hemostatic tamponade therapy for the management of
      life-threatening hemoptysis.
AB  - STUDY OBJECTIVES: Massive hemoptysis is a life-threatening condition. Therapeutic
      strategies such as interventional angiography, surgery, and/or bronchoscopy have
      been applied in the clinical setting with variable results. We investigated the
      efficacy of bronchoscopy-guided topical hemostatic tamponade therapy (THT) using
      oxidized regenerated cellulose (ORC) mesh in the management of life-threatening
      hemoptysis. DESIGN: Seventy-six consecutive patients underwent emergency
      bronchoscopy for massive hemoptysis. Fifty-seven patients (75%) had persistent
      endobronchial bleeding despite bronchoscopic wedging technique, cold saline
      solution lavage, and instillation of regional vasoconstrictors. These patients
      subsequently underwent THT according to the same procedure. SETTING: Teaching
      hospital, bronchoscopy unit of a 300-bed tertiary pulmonary referral center.
      RESULTS: THT with ORC was successfully performed on 56 of 57 patients (98%) with
      an immediate arrest of hemoptysis. All patients successfully treated with THT
      remained free of hemoptysis for the first 48 h. None required intensive care
      support or immediate surgery. Mean procedure time (+/- SD) of THT was 11.5 +/-
      4.2 min. Recurrence of hemoptysis that was characterized as being mild (< 30 mL)
      to moderate (30 to 100 mL) developed in six patients (10.5%) 3 to 6 days after
      THT. Post-obstructive pneumonia developed in five subjects (9%) after endoscopic
      THT. A subgroup of patients (n = 14) underwent bronchoscopic follow-up 4 weeks
      after discharge. The ORC mesh was absorbed in all of these patients without signs
      of foreign body reaction. CONCLUSIONS: Endobronchial THT using ORC is a safe and
      practicable technique in the management of life-threatening hemoptysis with a
      high success and a relatively low complication rate.

PMID- 15947329
TI  - Follow-up study on pulmonary function and lung radiographic changes in
      rehabilitating severe acute respiratory syndrome patients after discharge.
AB  - OBJECTIVES: To follow-up on the changes in lung function and lung radiographic
      pictures of severe acute respiratory syndrome (SARS) patients discharged from
      Xiaotangshan Hospital in Beijing (by regularly receiving examination), and to
      analyze retrospectively the treatment strategy in these patients. METHODS:
      Surviving SARS patients were seen at least twice within 3 months after discharge
      and underwent SARS-associated coronavirus (SARS-CoV) IgG antibody testing,
      pulmonary function testing, and chest radiography and/or high-resolution CT
      (HRCT) examinations at Chinese PLA General Hospital. The treatments received at
      Xiaotangshan Hospital were analyzed retrospectively and were correlated to later
      status. RESULTS: Positive SARS-Co virus IgG antibody results were seen in 208 of
      258 patients, with 21.3% (55 of 258 patients) still having a pulmonary diffusion
      abnormality (D(LCO) < 80% of predicted). By comparing the 155 survivors with
      positive SARS-CoV IgG antibody results and D(LCO) > or = 80% predicted with the
      50 patients with negative SARS-CoV IgG results, we found that 53 patients with
      positive SARS-CoV IgG results and a lung diffusion abnormality had endured a much
      longer course of fever and received larger doses of glucocorticoid, as well as
      higher ratios of oxygen inhalation and noninvasive ventilation treatment. For
      these patients, 51 of 53 patients with positive SARS-CoV IgG results and a lung
      diffusion abnormality underwent pulmonary function testing after approximately 1
      month. D(LCO) improved in 80.4% of patients (41 of 51 patients). Of the patients
      with a lung diffusion abnormality, 40 of 51 patients showed lung fibrotic changes
      in the lung image examination and 22 patients (55%) showed improvement in lung
      fibrotic changes 1 month later. CONCLUSION: These findings suggest that lung
      fibrotic changes caused by SARS disease occurred mostly in severely sick patients
      and may be self-rehabilitated. D(LCO) scores might be more sensitive than HRCT
      when evaluating lung fibrotic changes.

PMID- 15947330
TI  - The effect of body mass index on patient outcomes in a medical ICU.
AB  - STUDY OBJECTIVES: To examine the effect of patient body mass index (BMI) on
      outcome in intensive care. DESIGN: In a prospective study, the patients were
      classified into groups based on the calculated BMI, as follows: BMI < 19.0 (n =
      350), > or = 19.0 and < 25.0 (n = 663), > or = 25.0 and < 29.9 (n = 585), > or =
      30.0 and < 40.0 (n = 396), and > or = 40.0 (n = 154). Groups were compared by
      age, APACHE (acute physiology and chronic health evaluation) II score, mortality,
      ICU length of stay (LOS), hospital LOS, number receiving ventilation, and
      ventilator-days. Adverse events including nosocomial pneumonia, ventilator-days
      per patient, failed extubations, and line-related complications were recorded.
      SETTING: The study was conducted in a 9-bed medical ICU of a 650-bed tertiary
      care hospital. MEASUREMENTS: Height and weight were prospectively recorded for
      the first ICU admission during a hospital stay. RESULTS: Between January 1, 1997,
      and August 1, 2001, 2,148 of 2,806 patients admitted to the ICU had height and
      weight recorded. There were no differences in APACHE II score, mortality, ICU
      LOS, hospital LOS, number receiving ventilation, ventilator-days, average total
      cost, or average variable cost among the five groups. However, the severely obese
      patients were more frequently female and younger than those who were overweight
      and obese (p < 0.001). Adverse events were infrequent, but there were no
      differences between the obese/very obese compared with others. CONCLUSION: BMI
      has minimal effects on ICU outcome after patients are admitted to a critical care
      unit.

PMID- 15947331
TI  - Survival in amyotrophic lateral sclerosis with home mechanical ventilation: the
      impact of systematic respiratory assessment and bulbar involvement.
AB  - STUDY OBJECTIVES: To analyze (1) the impact of a protocol of early respiratory
      evaluation of the indications for home mechanical ventilation (HMV) in patients
      with amyotrophic lateral sclerosis (ALS), and (2) the effects of the protocol and
      of bulbar involvement on the survival of patients receiving noninvasive
      ventilation (NIV). DESIGN AND SETTING: Retrospective study in a tertiary care
      referral center. PATIENTS: HMV was indicated in 86 patients with ALS, with 22
      patients (25%) presenting with intolerance to treatment associated with bulbar
      involvement. Treatment with HMV had been initiated in 15 of 64 patients prior to
      initiating the protocol (group A) and in the remaining 49 patients after protocol
      initiation (group B). RESULTS: In group A, the majority of patients began
      treatment with HMV during an acute episode requiring ICU admission (p = 0.001)
      and tracheal ventilation (p = 0.025), with a lower percentage of patients
      beginning HMV treatment without respiratory insufficiency (p = 0.013). No
      significant differences in survival rates were found between groups A and B among
      patients treated with NIV. Greater survival was observed in group B (p = 0.03)
      when patients with bulbar involvement were excluded (96%). Patients without
      bulbar involvement at the start of therapy with NIV presented a significantly
      better survival rate (p = 0.03). Multivariate analysis showed bulbar involvement
      to be an independent prognostic factor for survival (relative risk, 1.6; 95%
      confidence interval, 1.01 to 2.54; p = 0.04). No significant differences in
      survival were observed between patients with bulbar involvement following
      treatment with NIV and those with intolerance, except for the subgroup of
      patients who began NIV treatment with hypercapnia (p = 0.0002). CONCLUSIONS:
      Early systematic respiratory evaluation in patients with ALS is necessary to
      improve the results of HMV. Further studies are required to confirm the benefits
      of NIV treatment in patients with bulbar involvement, especially in the early
      stages.

PMID- 15947332
TI  - Effect of granulocyte-monocyte colony-stimulating factor therapy on leukocyte
      function and clearance of serious infection in nonneutropenic patients.
AB  - STUDY OBJECTIVE: Impaired leukocyte function in patients with serious infections
      may increase mortality. Granulocyte-monocyte colony-stimulating factor (GM-CSF)
      broadly activates peripheral monocytes and neutrophils. We performed a clinical
      trial of GM-CSF in septic, hemodynamically stable patients to see whether GM-CSF
      treatment improved leukocyte function and mortality. DESIGN: Randomized,
      unblinded, placebo-controlled, prospective study. SETTING: A 600-bed academic
      tertiary care center with a 120-bed ICU census with a high proportion of
      immunocompromised, solid-organ transplant recipients. PATIENTS: Forty adult
      patients with infections meeting the criteria for the systemic inflammatory
      response syndrome but without hemodynamic instability or shock. INTERVENTIONS:
      Patients with sepsis and a documented infection were randomized to a 72-h
      infusion of GM-CSF (125 microg/m2) or placebo. MEASUREMENTS AND MAIN RESULTS: GM
      CSF infusion caused the up-regulation of the beta2-integrin adhesion molecule
      CD11b and the appearance of the activated ("sticky" or "avid") form of the
      molecule on circulating neutrophils and monocytes. CD11b density and avidity
      increases in response to the administration of tumor necrosis factor-alpha were
      blunted prior to treatment in these patients with serious infection. GM-CSF
      partially repaired this blunted response on both monocytes and neutrophils. It
      also caused the down-regulation of the adhesion molecule L-selectin on
      neutrophils and the up-regulation of human leukocyte antigen on monocytes. These
      changes were consistent with a broad activation of the circulating leukocyte
      pool. Although mortality and organ failure scores were similar in both groups,
      infection resolved significantly more often in patients receiving GM-CSF.
      CONCLUSIONS: GM-CSF infusion up-regulated the functional markers of inflammation
      on circulating neutrophils and monocytes and was associated with both the
      clinical and microbiological resolution of infection. There was no detectable
      exacerbation of sepsis-related organ failure or other deleterious side effects
      with the administration of this proinflammatory agent to patients with serious
      infections.

PMID- 15947333
TI  - Improving the ICU: part 1.
AB  - ICUs are a vital component of modern health care. Improving ICU performance
      requires that we shift from a paradigm that concentrates on individual
      performance to a different paradigm that emphasizes the need to assess and
      improve ICU systems and processes. This is the first part of a two-part treatise.
      It discusses existing problems in ICU care, and the methods for defining and
      measuring ICU performance.

PMID- 15947334
TI  - Improving the ICU: part 2.
AB  - ICUs are a vital but troubled component of modern health-care systems. Improving
      ICU performance requires that we shift from a paradigm that concentrates on
      individual performance, to a systems-oriented approach that emphasizes the need
      to assess and improve the ICU systems and processes that hinder the ability of
      individuals to perform their jobs well. This second part of a two-part treatise
      establishes a practical framework for performance improvement and examines
      specific strategies to improve ICU performance, including the use of information
      systems.

PMID- 15947335
TI  - Treatment preferences for resuscitation and critical care among homeless persons.
AB  - CONTEXT: Homeless people are at increased risk of critical illness and are less
      likely to have surrogate decision makers when critically ill. Consequently,
      clinicians must make decisions independently or with input from others such as
      ethics committees or guardians. No prior studies have examined treatment
      preferences of homeless to guide such decision makers. DESIGN: Interviewer
      administered, cross-sectional survey of homeless persons. SETTING: Homeless
      shelters in Seattle, WA. PARTICIPANTS: Two hundred twenty-nine homeless
      individuals with two comparison groups: 236 physicians practicing in settings
      where they are likely to provide care for homeless persons and 111 patients with
      oxygen-dependent COPD. MEASUREMENTS: Participants were asked whether they would
      want intubation with mechanical ventilation or cardiopulmonary resuscitation in
      their current health, if they were in a permanent coma, if they had severe
      dementia, or if they were confined to bed and dependent on others for all care.
      RESULTS: Homeless men were more likely to want resuscitation than homeless women
      (p < 0.002) in coma and dementia scenarios. Homeless men and women were both more
      likely to want resuscitation in these scenarios than physicians (p < 0.001).
      Nonwhite homeless were more likely to want resuscitation than white homeless
      people (p < 0.033), and both were more likely to want resuscitation than
      physicians (p < 0.001). Homeless are also more likely to want resuscitation than
      patients with COPD. The majority (80%) of homeless who reported not having family
      or not wanting family to make medical decisions prefer a physician make decisions
      rather than a court-appointed guardian. CONCLUSIONS: Homeless persons are more
      likely to prefer resuscitation than physicians and patients with severe COPD.
      Since physicians may be in the position of making medical decisions for homeless
      patients and since physicians are influenced by their own preferences when making
      decisions for others, physicians should be aware that, on average, homeless
      persons prefer more aggressive care than physicians. Hospitals serving homeless
      individuals should consider developing policies to address this issue.

PMID- 15947336
TI  - Barriers and facilitators to end-of-life care communication for patients with
      COPD.
AB  - OBJECTIVE: Patients with COPD frequently do not discuss end-of-life care with
      physicians; therefore, we sought to identify the barriers and facilitators to
      this communication as a first step to overcoming barriers and capitalizing on
      facilitators. DESIGN: Fifteen barriers and 11 facilitators to patient-physician
      communication about end-of-life care were generated from focus groups of patients
      with COPD. We subsequently conducted a cross-sectional study of 115 patients with
      oxygen-dependent COPD and their physicians to identify the common barriers and
      facilitators and examine the association of these barriers and facilitators with
      communication about end-of-life care. PARTICIPANTS AND SETTING: Patients with
      oxygen-dependent COPD were recruited from clinics at a university, county, and
      Veterans Affairs teaching hospital, and an oxygen delivery company. We also
      recruited the physician identified by each patient as the doctor primarily
      responsible for their lung disease. MEASUREMENTS AND RESULTS: Patients were
      interviewed by trained research interviewers. Physician data collection was
      completed by mail survey. Participation rates were 40% for patients and 86% for
      physicians. Only 32% of patients reported having a discussion about end-of-life
      care with their physician. Two of 15 barriers and 8 of 11 facilitators were
      endorsed by > 50% of patients. The most commonly endorsed barriers were "I'd
      rather concentrate on staying alive," and "I'm not sure which doctor will be
      taking care of me." Two barriers were significantly associated with lack of
      communication, as follows: "I don't know what kind of care I want," and "I'm not
      sure which doctor will be taking care of me." The greater the number of barriers
      endorsed by patients, the less likely they were to have discussed end-of-life
      care with physicians (p < 0.01), suggesting the validity of these barriers.
      Conversely, the more facilitators, the more likely patients were to report having
      had end-of-life discussions with their physicians (p < 0.001). CONCLUSION:
      Although patients endorsed many barriers and facilitators, few barriers were
      endorsed by most patients. Barriers and facilitators associated with
      communication are targets for interventions to improve end-of-life care, but such
      interventions will likely need to address the specific barriers relevant to
      individual patient-physician pairs.

PMID- 15947337
TI  - Comparative impact of morbid obesity vs heart failure on cardiorespiratory
      fitness.
AB  - BACKGROUND: We are in the midst of an obesity pandemic. Morbid obesity is
      associated with dyspnea on exertion and higher overall mortality rates. The
      relations between measures of cardiorespiratory fitness in morbidly obese persons
      compared to those with heart failure are unknown. METHODS: We compared
      cardiorespiratory fitness in patients with morbid obesity (n = 43) and
      established systolic dysfunction heart failure (n = 235), and in age-matched
      medical control subjects (n = 222) who had been referred for diagnostic exercise
      testing with simultaneous metabolic measurements. Only patients who completed an
      adequate test for maximum exertion manifested by a respiratory exchange ratio of
      > or = 1.10 were included in the study. RESULTS: The mean (+/- SD) body mass
      index (BMI) values for the three groups were 47.8 +/- 5.1, 30.1 +/- 5.7, and 33.8
      +/- 9.0, respectively (p < 0.0001 for comparisons between morbidly obese patients
      and each comparator). The mean left ventricular ejection fraction for the heart
      failure group was 21.5 +/- 8.4%. Despite achieving higher peak heart rate and BP
      values, the morbidly obese patients had a mean maximum oxygen uptake (V(O2)max)
      that was similar to that of those with heart failure (17.8 +/- 3.6 vs 16.5 +/-
      5.6 mL/kg/min, respectively; p = 0.14) and was considerably lower than that of
      the control group (17.8 +/- 3.6 vs 21.3 +/- 8.2 mL/kg/min, respectively; p =
      0.007). In addition, among subjects in the control group, there was a graded
      inverse relation between BMI and V(O2)max. CONCLUSIONS: Morbidly obese
      individuals have severely reduced cardiorespiratory fitness that is similar to
      those with established systolic dysfunction heart failure. In addition, in those
      persons who are referred for stress testing for medical reasons, there is an
      inverse graded relationship between BMI and cardiorespiratory fitness. These data
      suggest that the impairment in V(O2)max in morbidly obese persons is related to
      BMI and possibly to other factors that impair peak cardiac performance. These
      findings are consistent with overall higher expected mortality in morbidly obese
      persons.

PMID- 15947339
TI  - A hydrodynamic study of pleural drainage systems: some practical consequences.
AB  - BACKGROUND: A pleural drainage system must be capable of efficiently evacuating
      the air or fluids from the pleural cavity so that adequate lung reexpansion can
      take place. The air flow and negative pressure of the system will depend on the
      particular design of each model. This experimental study analyzes the
      specifications and performance of the pleural drainage systems currently on the
      market. METHODS: Thirteen models of pleural drainage systems connected to wall
      suction were examined. The models were classified into the following three
      groups: dry systems; wet systems; and single-chamber systems. We determined the
      ambient air flow and the negative pressure generated according to the suction
      level. The components of each model are also described. RESULTS: Under normal
      conditions, dry (except for the Sentinel Seal; Sherwood Medical; Tullamore,
      Ireland), wet, and single-chamber systems reach similar air flow rates (17 to 30,
      24 to 27, and 22 to 28 L/min, respectively). With higher wall suction levels, wet
      systems increase the air flow (26 to 49 L/min) but the negative pressure becomes
      unstable because of the water loss phenomenon, dry systems increase the air flow
      (29 to 50 L/min) without modifying the regulator pressure, and single-chamber
      systems also raise the air flow (45 to 51 L/min) but increase the negative
      pressure. When there is an air leak, dry systems (except for the Sentinel Seal)
      lose less negative pressure than the other systems. CONCLUSIONS: The functioning
      of these systems can be optimized only by applying a suitable wall suction level
      adjusted to each case. Although the three types of systems are capable of
      evacuating adequate air flow rates, the negative pressure and the capacity to
      maintain it in the presence of an air leak are different in each system. Being
      fitted with valves and not water compartments makes the dry systems the safest
      and the ideal for use when the patient has to be moved.

PMID- 15947338
TI  - Reloading the diaphragm following mechanical ventilation does not promote injury.
AB  - STUDY OBJECTIVE: Mechanical ventilation (MV) is used clinically to treat patients
      who are incapable of maintaining adequate alveolar ventilation. Prolonged MV is
      associated with diaphragmatic atrophy and a decrement in maximal specific force
      production (P(O)). Collectively, these alterations may predispose the diaphragm
      to injury on the return to spontaneous breathing (ie, reloading). Therefore,
      these experiments tested the hypothesis that reloading the diaphragm following MV
      exacerbates MV-induced diaphragmatic contractile dysfunction, while causing
      muscle fiber membrane damage and inflammation. METHODS: To test this postulate,
      Sprague-Dawley rats were randomly assigned to the following groups: (1) control;
      (2) 24 h of controlled MV; and (3) 24 h of controlled MV followed by 2 h of
      anesthetized spontaneous breathing. Controls were anesthetized in the short term
      but were not exposed to MV, whereas MV animals were anesthetized,
      tracheostomized, and ventilated. Reloaded animals remained under anesthesia, but
      were removed from MV and returned to spontaneous breathing for 2 h. RESULTS:
      Compared to the situation with control animals, MV resulted in a 26% decrement in
      diaphragmatic specific P(O) without muscle fiber membrane damage, as measured by
      an increase in membrane permeability (using the procion orange technique).
      Further, there were no increases in neutrophil or macrophage influx. Two hours of
      reloading did not exacerbate MV-induced diaphragmatic contractile dysfunction or
      cause fiber membrane damage, but increased neutrophil infiltration,
      myeloperoxidase activity, and muscle edema. CONCLUSION: We conclude that the
      return to spontaneous breathing following 24 h of controlled MV does not
      exacerbate MV-induced diaphragm contractile dysfunction or result in fiber
      membrane damage, but increases neutrophil infiltration.

PMID- 15947340
TI  - Evaluation of an abbreviated adenosine monophosphate bronchial challenge.
AB  - RATIONALE: Airway hyperresponsiveness to adenosine monophosphate (AMP) has been
      validated as a surrogate marker for airway inflammation. We wished to know
      whether an abbreviated challenge at the final threshold dose would produce the
      same fall in FEV1 as a full, conventional dose-response challenge. METHODS:
      Seventeen patients with mild-to-moderate asthma (mean FEV1, 75.5% predicted)
      attended for a full dose-response protocol, where the highest concentration of
      AMP to produce > 20% fall in FEV1 was noted, along with the maximum percentage
      fall and recovery time. Patients returned within 2 days for a further challenge,
      when they received only the highest concentration (as a single bolus) reached on
      the previous visit. RESULTS: The mean (+/- SEM) percentage fall in FEV1 after the
      full challenge was 25.5 +/- 1.3%, and after the abbreviated challenge was 9.4 +/-
      2.4%. The mean recovery after the full challenge was 28.13 +/- 4.65 min, and
      after the abbreviated test was 10.81 +/- 4.27 min. CONCLUSION: An abbreviated
      challenge using a single bolus dose of AMP grossly underestimates bronchial
      hyperresponsiveness. Although the pharmacologic half-life of AMP is short (90 s),
      the lesser response and shortened recovery with the abbreviated challenge suggest
      a more prolonged physiologic half-life, which in turn may have implications for
      abbreviated challenge protocols.

PMID- 15947341
TI  - Video-assisted thoracoscopic surgery for primary spontaneous pneumothorax:
      evaluation of indications and long-term outcome compared with conservative
      treatment and open thoracotomy.
AB  - STUDY OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) is effective for
      primary spontaneous pneumothorax. We sought to evaluate the outcome of VATS
      compared to conservative treatment and open thoracotomy, and to discuss the
      indications for VATS in primary spontaneous pneumothorax. DESIGN: Retrospective
      study. PATIENTS AND INTERVENTIONS: Primary spontaneous pneumothorax was diagnosed
      in 281 consecutive patients between January 1989 and April 2001. Mean age was
      29.1 years. Mean follow-up period was 78.3 months (range, 13 to 163 months). For
      these patients, conservative treatment, open thoracotomy, or VATS were performed,
      and the outcomes of the three treatments were evaluated. If recurrence occurred,
      outcome of treatment for the recurrence was also evaluated according to the
      number of times of recurrence. RESULTS: Recurrences were observed in 109 of 281
      patients (38.8%). Forty-three patients (15.3%) had repeat recurrences. Regarding
      the outcome of the first episode, recurrence rates were 54.7% for conservative
      treatment, 7.7% for open thoracotomy, and 10.3% for VATS. Recurrence rates after
      the second episode were 60.3% for conservative treatment, 0% for open
      thoracotomy, and 18.6% for VATS. Overall recurrence rates of each treatment were
      56.4%, 3.0%, and 11.7%, respectively. There was no statistical difference between
      the open thoracotomy and VATS groups (p = 0.15). Hospital stays from operation
      until discharge were 11.5 days for open thoracotomy and 4.1 days for VATS (p <
      0.001). CONCLUSION: The outcomes of VATS were very good compared to conservative
      treatment and equal to those of the open thoracotomy, not only for the first
      episode but also for the case of recurrence. In terms of low morbidity, low
      invasiveness, and cosmetic issues, VATS is superior to open thoracotomy. VATS is
      standard in cases of recurrence and should be considered for treatment at the
      first episode.

PMID- 15947342
TI  - Clinical significance of the infection-free interval in the management of acute
      bacterial exacerbations of chronic bronchitis.
AB  - Rational and appropriate antibiotic use for patients with acute exacerbation of
      chronic bronchitis (AECB) is a major concern, as approximately half of these
      patients do not have a bacterial infection. Typically, the result of
      antimicrobial therapy for patients with acute bacterial exacerbation of chronic
      bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute
      symptoms. However, the length of time before the next bacterial exacerbation can
      be another important variable, as the frequency of exacerbations will affect the
      overall health of the patient and the rate of lung deterioration over time.
      Clinical trials comparing antimicrobial therapies commonly measure resolution of
      symptoms in AECB patients as the primary end point, regardless of whether the
      exacerbation is documented as bacterial in nature. Ideally, the scientific
      approach to assessing the efficacy of antibiotic therapy for ABECB should include
      a measurement of acute bacterial eradication rates in patients with documented
      bronchial bacterial infection followed by measurement of the infection-free
      interval (IFI), ie, the time to the next ABECB. The use of these variables can
      provide a standard for comparing various antimicrobial therapies. As we learn
      more about how antibiotics can affect the IFI, treatment decisions should be
      adapted to ensure optimal management of ABECB for the long-term.

PMID- 15947343
TI  - CT-guided interstitial single-fraction brachytherapy of lung tumors: phase I
      results of a novel technique.
AB  - PURPOSES: To assess the safety of CT-guided brachytherapy of lung malignancies
      and to evaluate the initial therapeutic response. PATIENTS AND METHODS: Fifteen
      patients with 30 lung malignancies were included in this prospective phase I
      trial (metastases, 28; non-small cell lung cancers, 2). Pre-interventionally two
      patients had a vital capacity of < 80% (39% and 63%). These two patients, and one
      other, had FEV1 values of < 80% predicted (17%, 48%, and 64%). Tumors with a
      maximum diameter of 4 cm were treated with a single brachytherapy catheter that
      was positioned under CT-fluoroscopy. In two tumors with tumor diameters of 5.5
      and 6.5 cm, two applicators were used. In one patient with an 11-cm irregularly
      shaped tumor, nine catheters were inserted. Treatment planning for 192Ir
      brachytherapy was performed using three-dimensional CT data that were acquired
      after percutaneous applicator positioning. All procedures were performed under
      local anesthesia. A follow-up CT was performed 6 weeks later and every 3 months
      pos-tintervention. RESULTS: The mean diameter of the 30 lung tumors was 2 cm
      (range, 0.6 to 11 cm; median diameter, 1.5 cm). The minimal dose within the tumor
      margin was 20 Gy in all 30 tumors treated. Except for nausea in one patient and
      focal hemorrhage detected on CT in two patients, no acute adverse events were
      recorded. One patient developed an abscess at the previous tumor location 9
      months after treatment, which proved to be a local tumor recurrence. The median
      follow-up period was 5+ months with a local tumor control of 97%. CONCLUSION: The
      novel technique of CT-guided interstitial brachytherapy was safe for the
      treatment of lung tumors and yielded a very low complication rate. The initial
      data on therapeutic response are promising.

PMID- 15947344
TI  - Pulmonary vasculitis in behcet disease: a cumulative analysis.
AB  - STUDY OBJECTIVES: The aims of this study were to investigate the frequency of
      pulmonary problems in Behcet disease (BD), and to discuss lesser-known features
      of pulmonary BD such as clinical characteristics, analysis of prognosis, and
      evaluation of treatment options with respect to the previously published cases.
      DESIGN: We conducted a comprehensive review of the literature to analyze
      cumulated data about pulmonary involvement in BD. SETTING: We found 159 articles
      regarding pulmonary disease associated with BD in May 2003. PATIENTS: The
      evaluation of these articles demonstrated 598 pulmonary problems in 585 cases.
      RESULTS: Pulmonary artery aneurysms (PAAs) are the most common pulmonary lesion
      in BD, and these are almost always associated with hemoptysis. Seventy-eight
      percent of patients with aneurysms have concomitant extrapulmonary venous thrombi
      or thrombophlebitis. Other pulmonary problems are reported in BD, and these are
      principally related to vascular lesions and radiologic abnormalities.
      CONCLUSIONS: Pulmonary vascular problems, either PAA or involvement of small
      sized vessels, are the main pulmonary disorders in BD. Immunopathologic findings
      indicate that the underlying pathogenesis is pulmonary vasculitis, which may
      result in thrombosis, infarction, hemorrhage, and PAA formation. Patients with
      small nonspecific radiologic abnormalities should be followed up closely since
      early diagnosis of vascular lesions may be life-saving. Immunosuppression is the
      main therapy for the treatment of a vasculitis. It is important that pulmonary
      angiitis is not mistaken for pulmonary thromboembolic disease since fatalities
      have occurred in BD shortly after initiation of anticoagulation/thrombolytic
      treatment.

PMID- 15947345
TI  - Flow-mediated vasodilation: a diagnostic instrument, or an experimental tool?
AB  - Brachial arterial flow-mediated dilation (FMD), assessed by high-resolution
      ultrasonography, reflects endothelium-dependent vasodilator function. FMD is
      diminished in patients with atherosclerosis and with coronary risk factors, and
      improves with risk-reduction therapy. Therefore, the measurement of FMD can be a
      good prognostic instrument in preventive cardiology, is useful to predict short
      term postoperative cardiovascular events in a high-risk population and to assess
      long-term cardiovascular risk in a lower risk population, and is an excellent
      experimental tool to detect changes in endothelial function after new therapeutic
      interventions. In this review article, the pathophysiology of FMD, based on
      reactive hyperemia, is extensively discussed. Furthermore, an overview is given
      of the actual clinical indications of FMD measurement.

PMID- 15947346
TI  - An unusual radiologic presentation of an uncommon bronchogenic lung carcinoma.

PMID- 15947347
TI  - A 55-year-old smoker with a persistent right lower lobe infiltrate.

PMID- 15947348
TI  - Visceral pleural perforation in two cases of ultrathin bronchoscopy.
AB  - Recently, ultrathin bronchoscopes with a thinner external diameter, greater
      visual range, improved visibility, and a larger working channel have been
      developed. The utility of a 2.8-mm diameter ultrathin bronchoscope in diagnosing
      peripheral pulmonary nodules has been reported by some authors. While the
      feasibility of approaching peripheral pulmonary lesions is attractive, peculiar
      complications that have not been experienced with standard bronchoscopy may
      occur. We report two cases in which pneumothoraces occurred because their
      visceral pleuras were perforated with an ultrathin bronchoscope during the
      procedure. The peculiar mechanism of pneumothorax in relation to ultrathin
      bronchoscopy is discussed.

PMID- 15947349
TI  - Small cell carcinoma of the lung exclusively localized within the left descending
      pulmonary artery.
AB  - We encountered a 69-year-old woman displaying a filling defect within the left
      descending pulmonary artery (PA) on a chest CT scan and pulmonary angiography. A
      subsequent 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography
      (PET) scan demonstrated focal uptake in the left hilum. A cytologic examination
      of transbronchial needle aspiration specimens revealed small cell carcinoma. The
      patient underwent concurrent radiation therapy and chemotherapy with cisplatin
      and etoposide, resulting in tumor shrinkage and recanalization of the involved
      PA. This is the first case of small cell carcinoma localized exclusively within
      the PA, and positive findings on FDG-PET facilitated the unexpected diagnosis.

PMID- 15947350
TI  - Silicone embolism syndrome: a case report, review of the literature, and
      comparison with fat embolism syndrome.
AB  - Liquid silicone is an inert material that is utilized for cosmetic procedures by
      physicians as well as illegally by nonmedical personnel. We present a case report
      and collated clinical findings of 32 other patients who were hospitalized after
      illegal silicone injections. Symptoms and signs of the "silicone syndrome"
      included dyspnea, fever, cough, hemoptysis, chest pain, hypoxia, alveolar
      hemorrhage, and altered consciousness. Bilateral patchy alveolar infiltrates were
      present on the chest radiographs, and silicone pulmonary emboli were detected in
      all the patients. The patients could be divided into two groups based on the
      initial presentation and clinical outcome. Twenty-seven patients in group 1
      presented predominantly with respiratory symptoms, and 93% of patients were
      discharged home within 3 weeks. Six patients (group 2) presented with severe
      neurologic findings, and experienced rapid deterioration and 100% mortality. The
      clinical findings after silicone embolism are very similar to the published
      reports of fat embolism, including hypoxemia in 92% of patients with silicone
      embolism (patients with fat embolism, 56 to 96%), dyspnea in 88% of patients
      (patients with fat embolism, 56 to 75%), fever in 70% of patients (patients with
      fat embolism, 23 to 67%), alveolar hemorrhage in 64% of patients (patients with
      fat embolism, 66%), neurologic symptoms in 33% of patients (patients with fat
      embolism, 22 to 86%), petechiae in 18% of patients (patients with fat embolism,
      20 to 50%), chest pain in 15% of patients (patients with fat embolism, 26%), and
      mortality in 24% of patients (patients with fat embolism, 5 to 20%). The
      similarities among the mode of injury to the lung, the clinical findings, and the
      high incidence of alveolar hemorrhage suggest a common pathogenesis of silicone
      and fat embolism syndromes. We discuss the possibility that the activation of the
      coagulation system may be important in the development of these clinical
      syndromes.

PMID- 15947351
TI  - Should a renal dose of norepinephrine stimulate hyperfiltration in head trauma
      patients?

PMID- 15947352
TI  - Cardiovascular risks associated with beta-agonist therapy.

PMID- 15947353
TI  - Relationship of baseline glucose and mortality during medical critical illness?

PMID- 15947354
TI  - Allergic rhinitis as a risk factor for habitual snoring in children.

PMID- 15947355
TI  - Water immersion effects on severe diaphragm weakness.

PMID- 15947356
TI  - Postbronchoscopy fever in patients with nontuberculous mycobacterial lung
      disease.

PMID- 15947357
TI  - Dose capping enoxaparin is unjustified and denies patients with acute coronary
      syndromes a potentially effective treatment.

PMID- 15947358
TI  - Assessment of ventilation during the performance of elective endoscopic-guided
      percutaneous tracheostomy.

PMID- 15947359
TI  - Sputum eosinophils and bronchodilator reversibility: COPD or asthma?

PMID- 15947360
TI  - Association between epidermal growth factor receptor mutation and improved
      survival in never-smokers with primary adenocarcinoma of the lung.

PMID- 15947361
TI  - The intensivist shortage: put patients before politics.

PMID- 15947362
TI  - Eosinophilic pneumonia and arthritis.

PMID- 15947363
TI  - Using barrier filters to protect spirometer sensors from droplet deposition.

PMID- 15947364
TI  - Oxidative stress and cardiovascular complications in sleep apnea.

PMID- 15947365
TI  - Noninvasive imaging for the postoperative assessment of aortic coarctation
      patients.

PMID- 15947366
TI  - Daily hemodialysis improves survival in acute renal failure in the ICU.

PMID- 15947367
TI  - Comparison of helical CT scanning and MRI in the follow-up of adults with
      coarctation of the aorta.

PMID- 15947368
TI  - Risk vs benefits for thromboembolic disease after total joint surgery.

PMID- 15947369
TI  - The value of clopidogrel administered postoperatively following a non-ST-segment
      elevation acute coronary syndrome.

PMID- 15947370
TI  - FDA evaluation of antimicrobials: subgroup analysis.

PMID- 15947371
TI  - Cost-effective roles for nurse practitioners in secondary prevention.

PMID- 15947372
TI  - Primary care needs a new model of office practice.

PMID- 15947373
TI  - Prognosis in obesity.

PMID- 15947374
TI  - A middle way for rationing healthcare resources.

PMID- 15947375
TI  - Highly active antiretroviral therapy.

PMID- 15947376
TI  - COX 2 inhibitors, traditional NSAIDs, and the heart.

PMID- 15947379
TI  - Clinicians need better access to ethics advice, report says.

PMID- 15947377
TI  - Alcohol misuse, public health, and public policy.

PMID- 15947380
TI  - Support grows for retaining the opt-out to the 48 hour week.

PMID- 15947381
TI  - Too many heart patients discharged without follow-up care.

PMID- 15947382
TI  - Drug companies monitor web chat for adverse reaction reports.

PMID- 15947383
TI  - Pathologist in Sally Clark case suspended from court work.

PMID- 15947385
TI  - EU supports testing for children's drugs.

PMID- 15947386
TI  - Russia's youth faces worst crisis of homelessness and substance misuse since
      second world war.

PMID- 15947387
TI  - European GPs don't know how to deal with obesity epidemic.

PMID- 15947388
TI  - Meningitis vaccine recommended for three groups of young people.

PMID- 15947389
TI  - Loss of tobacco suit means 120 other cases will be dropped.

PMID- 15947390
TI  - Canadian Red Cross apologises for distributing HIV infected blood.

PMID- 15947391
TI  - GMC hearing opens into doctor at centre of organ retention scandal.

PMID- 15947392
TI  - Looking for new compounds in sea is endangering ecosystem.

PMID- 15947394
TI  - UN predicts that millennium development goals will be missed by a wide margin in
      Africa.

PMID- 15947396
TI  - Sudan arrests aid worker for "crimes against the state".

PMID- 15947398
TI  - Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or
      conventional non-steroidal anti-inflammatory drugs: population based nested case
      control analysis.
AB  - AIMS: To determine the comparative risk of myocardial infarction in patients
      taking cyclo-oxygenase-2 and other non-steroidal anti-inflammatory drugs (NSAIDs)
      in primary care between 2000 and 2004; to determine these risks in patients with
      and without pre-existing coronary heart disease and in those taking and not
      taking aspirin. DESIGN: Nested case-control study. SETTING: 367 general practices
      contributing to the UK QRESEARCH database and spread throughout every strategic
      health authority and health board in England, Wales, and Scotland. SUBJECTS: 9218
      cases with a first ever diagnosis of myocardial infarction during the four year
      study period; 86 349 controls matched for age, calendar year, sex, and practice.
      OUTCOME MEASURES: Unadjusted and adjusted odds ratios with 95% confidence
      intervals for myocardial infarction associated with rofecoxib, celecoxib,
      naproxen, ibuprofen, diclofenac, and other selective and non-selective NSAIDS.
      Odds ratios were adjusted for smoking status, comorbidity, deprivation, and use
      of statins, aspirin, and antidepressants. RESULTS: A significantly increased risk
      of myocardial infarction was associated with current use of rofecoxib (adjusted
      odds ratio 1.32, 95% confidence interval 1.09 to 1.61) compared with no use
      within the previous three years; with current use of diclofenac (1.55, 1.39 to
      1.72); and with current use of ibuprofen (1.24, 1.11 to 1.39). Increased risks
      were associated with the other selective NSAIDs, with naproxen, and with non
      selective NSAIDs; these risks were significant at < 0.05 rather than < 0.01 for
      current use but significant at < 0.01 in the tests for trend. No significant
      interactions occurred between any of the NSAIDs and either aspirin or coronary
      heart disease. CONCLUSION: These results suggest an increased risk of myocardial
      infarction associated with current use of rofecoxib, diclofenac, and ibuprofen
      despite adjustment for many potential confounders. No evidence was found to
      support a reduction in risk of myocardial infarction associated with current use
      of naproxen. This is an observational study and may be subject to residual
      confounding that cannot be fully corrected for. However, enough concerns may
      exist to warrant a reconsideration of the cardiovascular safety of all NSAIDs.

PMID- 15947400
TI  - Bell's palsy.

PMID- 15947399
TI  - Differences in outcomes of patients with congestive heart failure prescribed
      celecoxib, rofecoxib, or non-steroidal anti-inflammatory drugs: population based
      study.
AB  - OBJECTIVES: To compare the risk of death and recurrent congestive heart failure
      in elderly patients prescribed celecoxib, rofecoxib, or non-steroidal anti
      inflammatory drugs (NSAIDs) and to determine whether there are class differences
      between celecoxib and rofecoxib. DESIGN: Population based retrospective cohort
      study. SETTING: Databases of hospital discharge summaries and prescription drug
      claims in Quebec. PARTICIPANTS: 2256 patients aged 66 or more prescribed
      celecoxib, rofecoxib, or an NSAID after an index admission for congestive heart
      failure between April 2000 and March 2002. MAIN OUTCOME MEASURES: Time to all
      cause death and recurrent congestive heart failure, combined and separately.
      RESULTS: The risk of death and recurrent congestive heart failure combined was
      higher in patients prescribed NSAIDs or rofexocib than in those prescribed
      celecoxib (hazard ratio 1.26, 95% confidence interval 1.00 to 1.57 and 1.27, 1.09
      to 1.49, respectively). The findings were similar when the outcomes were assessed
      separately. In pairwise analysis, the risks of death and recurrent congestive
      heart failure, combined and separate, were similar between patients prescribed
      NSAIDs and rofecoxib. CONCLUSIONS: Celecoxib seems safer than rofecoxib and
      NSAIDs in elderly patients with congestive heart failure. Differences were found
      among cyclo-oxygenase-2 inhibitors.

PMID- 15947401
TI  - Pregnancy and breast cancer.

PMID- 15947402
TI  - Public health in the aftermath of disasters.

PMID- 15947403
TI  - Prognosis without treatment as a modifier in health economic assessments.

PMID- 15947404
TI  - Self regulation must be made to work.

PMID- 15947405
TI  - "Right to die": no man (or woman) is an island.

PMID- 15947406
TI  - "Right to die": changing "right" to "duty" may focus debate.

PMID- 15947407
TI  - "Right to die": sensitivity and humility are needed when dealing with dying
      people.

PMID- 15947408
TI  - "Right to die": legal view of right to life and death could threaten philosophy
      of palliative care.

PMID- 15947409
TI  - Scottish model for surgical mortality used in Australasia.

PMID- 15947411
TI  - "Right to die": ...but context of limited resources can be encountered in
      developed countries too.

PMID- 15947412
TI  - "Right to die": situation is different in developing countries...

PMID- 15947413
TI  - Why clinicians are natural bayesians: clinicians have to be bayesians.

PMID- 15947414
TI  - Why clinicians are natural bayesians: is there a bayesian doctor in the house?

PMID- 15947415
TI  - Why clinicians are natural bayesians: bayesian confusion.

PMID- 15947416
TI  - Clarification: doctors did not accuse Indian authorities of massaging leprosy
      data.

PMID- 15947417
TI  - English surgeons may at last be about to become doctors: anyone for bolting on
      the German system?

PMID- 15947418
TI  - English surgeons may at last be about to become doctors: what about nurses with
      PhDs?

PMID- 15947419
TI  - Online music model could work for journals.

PMID- 15947420
TI  - Allergic challenge-elicited lipid bodies compartmentalize in vivo leukotriene C4
      synthesis within eosinophils.
AB  - Eosinophils are an important source of leukotriene (LT)C(4), which can be
      synthesized within lipid bodies-cytoplasmic organelles where eicosanoid formation
      may take place. Allergy-driven lipid body formation and function have never been
      investigated. Here, we studied the in vivo induction and role of lipid bodies
      within eosinophils recruited to sites of allergic inflammation. Using two murine
      models of allergic inflammation (asthma and pleurisy), we verified that parallel
      to the eosinophil influx, allergic challenge also induced lipid body formation
      within recruited eosinophils. Neutralizing antibodies to eotaxin/CCL11,
      RANTES/CCL5, or CCR3 partially inhibited lipid body formation within recruited
      eosinophils in the allergic pleurisy model. Likewise, intrapleural administration
      of RANTES or eotaxin also induced significant influx of eosinophils loaded with
      lipid bodies. By immunolabeling, we detected the presence of a key enzyme
      involved in the leukotriene metabolism-5-lipoxygenase-within eosinophil lipid
      bodies formed in vivo after allergen challenge. Furthermore, specific
      immunolocalization of newly formed LTC(4) demonstrated that lipid bodies were the
      sites of formation of this eicosanoid within infiltrating eosinophils. Therefore,
      allergic inflammation triggers in vivo formation of new lipid bodies within
      infiltrating eosinophils, a phenomenon largely mediated by eotaxin/RANTES acting
      via CCR3 receptors. Such in vivo allergen-driven lipid bodies function as
      intracellular compartments of LTC(4) synthesis.

PMID- 15947421
TI  - Tissue inhibitor of metalloproteinase-1 deficiency amplifies acute lung injury in
      bleomycin-exposed mice.
AB  - Bleomycin-induced lung injury triggers a profound and durable increase in tissue
      inhibitor of metalloproteinase (TIMP)-1 expression, suggesting a potential role
      for this antiproteinase in the regulation of lung inflammation and fibrosis. TIMP
      1 protein induction is spatially restricted to areas of lung injury as determined
      by immunohistochemistry. Using TIMP-1 null mutation mice, we demonstrate that
      TIMP-1 deficiency amplifies acute lung injury as determined by exaggerated
      pulmonary neutrophilia, hemorrhage, and vascular permeability compared with wild
      type littermates after bleomycin exposure. The augmented pulmonary neutrophilia
      observed in TIMP-1-deficient animals was not found in similarly treated TIMP-2
      deficient mice. Using TIMP-1 bone marrow (BM) chimeric mice, we observed that the
      TIMP-1-deficient phenotype was abolished in wild-type recipients of TIMP-1
      deficient BM but not in TIMP-1-deficient recipients of wild-type BM. Acute lung
      injury in TIMP-1-deficient mice was accompanied by exaggerated gelatinase-B
      activity in the alveolar compartment. TIMP-1 deficiency did not alter neutrophil
      chemotactic factor accumulation in the injured lung nor neutrophil migration in
      response to chemotactic stimuli in vivo or in vitro. Moreover, TIMP-1 deficiency
      did not modify collagen accumulation after bleomycin injury. Our results provide
      direct evidence that TIMP-1 contributes significantly to the regulation of acute
      lung injury, functioning to limit inflammation and lung permeability.

PMID- 15947422
TI  - Mechanical stretch alters alveolar type II cell mediator release toward a
      proinflammatory pattern.
AB  - Increased mechanical stretch of alveolar type II (ATII) cells occurs during
      mechanical ventilation. The effects of three patterns of stretching rat ATII
      cells (frequency [min-1]-Deltasurface area [%]: S40-13, S60-13, S40-30) were
      compared with those in static cultures at 12, 18, and 24 h. Cell viability and
      expression of cyclooxygenase-2,5-lipoxygenase, inducible nitric oxide synthase
      (iNOS), and endothelial nitric oxide synthase (eNOS) were characterized.
      Supernatants were analyzed for eicosanoids, nitrite, cytokines, and stimulatory
      effects on rat lymphocytes. S40-13 simulates normal breathing; the other patterns
      increased amplitude and frequency. There were no significant differences between
      S40-13 and static cultures. S60-13 only significantly increased the supernatant
      nitrite (11.2+/-1.6 versus 3.9+/-0.4 microM at 24 h). S40-30 significantly
      reduced the number of trypan blue-excluding cells, increased the supernatant
      concentration of TXB2 (4.1+/-0.61 versus 2.2+/-0.36 pg/ml), 6-keto-PGF1alpha
      (8.7+/-1.0 versus 6.7+/-0.52 pg/ml), cysteinyl-LT (12.2+/-2.0 versus 6.1+/-0.75
      pg/ml) and nitrite (7.2+/-1.7 versus 3.9+/-0.4 microM). S40-30 did not alter the
      release of tumor necrosis factor-alpha and monocyte chemotactic protein-1, but
      significantly reduced the concentration of the anti-inflammatory interleukin-10
      (20.8+/-13.3 versus 130+/-21.5 pg/ml). Expression of cyclooxygenase-2/5
      lipoxygenase was increased/decreased; expression of iNOS/eNOS was unchanged by
      high-amplitude stretch. Supernatants from S40-30 experiments caused lymphocyte
      activation measured by CD71 and CD54 surface expression. Continuing mechanical
      distension of ATII cells contributes to an inflammatory response by a shift in
      the balance of pro- and anti-inflammatory mediators.

PMID- 15947423
TI  - Characterization of GPRA, a novel G protein-coupled receptor related to asthma.
AB  - We recently identified a novel positional asthma susceptibility gene, GPRA, which
      belongs to the G protein-coupled receptor family. In the present studies, we show
      that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS)
      resulted in significant inhibition of cell growth. GPRA has several variants due
      to extensive alternative splicing. We observed that only the full-length
      variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into
      the plasma membrane, while the truncated proteins retain intracellular
      compartments. To clarify disease mechanism, we studied co-expression of the
      variants without finding any indication that truncated variants would inhibit the
      receptor transport into the plasma membrane. By using in situ hybridization and
      immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent
      expression of GPRA-A in the epithelia of several organs including bronchi and
      gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein
      expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that
      GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study
      provides evidence that GPRA might have functional relevance in modulating asthma
      by increased expression levels in the relevant tissues under diseased state and
      by potential inhibitory effect of GPRA-A activation on cell growth.

PMID- 15947424
TI  - Gob-5 is not essential for mucus overproduction in preclinical murine models of
      allergic asthma.
AB  - Overexpression of Gob-5 has previously been linked to goblet cell metaplasia and
      mucin overproduction in both in vitro and in vivo model systems. In this study,
      Gob-5 knockout mice were generated and their phenotype was evaluated in two
      established preclinical models of allergic asthma. We sought to determine whether
      the Gob-5-null animals could produce less mucus in response to allergic
      challenge, and whether this would have any impact on reducing goblet cell
      metaplasia and airway inflammation. We found that in the absence of a
      proinflammatory stimulus we could not detect an overt phenotypic difference
      between age and sex-matched knockout and wild-type animals. Allergic challenge
      with ovalbumin or intranasal administration of interleukin-13 produced a robust
      allergic response that was similar regardless of genotype. In addition, siRNA
      mediated knockdown of CLCA-1 in cultured lung epithelial cells failed to reduce
      mucin expression in vitro. Thus, in contrast to previously published reports, our
      findings show that Gob-5 expression is not essential for mucin overproduction in
      vitro or in murine models of allergic asthma. Furthermore, we have also exploited
      the use of gene expression array analysis to investigate the possibility that a
      compensatory mechanism, involving other genes, may act to override the
      requirement for Gob-5-mediated mucus overproduction.

PMID- 15947425
TI  - Prevalence of potential virulence markers in Polish Campylobacter jejuni and
      Campylobacter coli isolates obtained from hospitalized children and from chicken
      carcasses.
AB  - The pathogenicity of thermotolerant Campylobacter species, common food-borne
      pathogens, depends on certain factors unevenly distributed among strains of
      different origin. The prevalence of such markers has never been examined in a
      population of Polish Campylobacter strains of human and poultry origin.
      Therefore, we analysed the presence of the cadF, cdtA, cdtB and cdtC genes and
      the iam sequence in Campylobacter jejuni (n = 115) and Campylobacter coli (n =
      57) isolates from children with diarrhoea and from chicken carcasses. The cadF
      gene was present in nearly 100% of Campylobacter isolates tested, regardless of
      their origin or species. In contrast, the iam region was found in 83.3% and 100%
      of C. coli isolates from children and chickens, respectively, but in only 1.6%
      and 54.7%, respectively, of C. jejuni isolates. Similarly, the detection rates of
      cdt genes varied between human and chicken isolates. All three cdt genes were
      found in nearly all C. jejuni isolates from both children and chickens, but in
      only 5.6% of human C. coli isolates as compared to 87.2% of chicken C. coli
      isolates. This different distribution of genetic markers between human and
      chicken isolates indicates that some Campylobacter infections in children may
      have additional sources other than contaminated chicken meat.

PMID- 15947426
TI  - All subtypes of the cytotoxin VacA adsorb to the surface of Helicobacter pylori
      post-secretion.
AB  - The major secreted virulence factor of Helicobacter pylori, the vacuolating
      cytotoxin VacA, is known to insert into eukaryotic membranes and has been
      observed in association with the surface of H. pylori cells that are actively
      producing it. Here, it is demonstrated that VacA is capable of interacting with
      the surface of H. pylori and Escherichia coli after secretion. It is shown that
      this interaction is resistant to disruption of electrostatic and hydrophobic
      forces, and that it appears to occur despite truncation of LPS and the removal of
      trypsin-accessible surface proteins. Adsorption to bacterial cell surfaces was
      independent of the VacA subtype, suggesting that it is not mediated through
      recognition of a known receptor by the VacA p58 subunit. Similarly, adsorption to
      bacterial cell surfaces is unlikely to be instigated by the extreme N-terminus of
      VacA, since a hydrophilic extension at this location that is known to disrupt
      VacA-induced vacuolation did not interfere with adsorption to H. pylori cells.

PMID- 15947427
TI  - Phosphotidylinositol-3 kinase-mediated signals in mice immunized with the 57 kDa
      major antigenic outer-membrane protein of Shigella dysenteriae type 1.
AB  - Antigen-specific T-cell signalling via T-cell antigen receptor stimulation was
      carried out in BALB/c mice immunized with the 57 kDa major antigenic component of
      Shigella dysenteriae 1 outer-membrane proteins. In presence of anti-CD3, the 57
      kDa antigen was found to increase the level of IL-2 significantly instead of IL
      4. IL-2 production in T cells was consistent with an increase in intracellular
      free Ca(2+) [(Ca(2+))i] concentration. The antigen-specific modulation was
      observed during T-cell signalling, with enhanced release of [(Ca(2+))i]. IL-2
      receptor stimulation via IL-2 did not significantly induce the release of IL-2
      with consistent intracellular Ca(2+) production. Furthermore, the protein
      tyrosine kinase was activated during anti-CD3 stimulation, which up-regulated the
      phosphatidylinositol kinase of p85-mediated serine kinase protein kinase-C of
      p70. Phosphoinositide-specific kinases are regulated by the phosphorylation of
      tyrosine kinase through the activation of the T-cell antigen receptor. The above
      findings indicate that phosphotidylinositol-3 kinase-mediated signals are up
      regulated through [(Ca(2+))i], which is essential for Th1-type responses.

PMID- 15947428
TI  - Characterization of Trichosporon species isolated from clinical specimens in
      Kuwait.
AB  - Invasive trichosporonosis is an emerging infection of severely immunocompromised
      patients. It is principally caused by Trichosporon asahii, although some other
      species of the genus have also been implicated in the aetiology. In this work, 29
      clinical isolates of Trichosporon species recovered from 29 different patients
      over a 6-year period were studied for phenotypic and genotypic characteristics.
      Two morphotypes were recognized on the basis of colony characteristics. The
      colonies of 25 isolates appeared flat and centrally wrinkled, while the other
      four isolates appeared dry and irregularly folded or verrucosed. Based on
      substrate assimilation profiles, all 29 isolates were identified as T. asahii
      using the Vitek 2 system. However, PCR amplification of rRNA gene sequences
      identified only 25 of the 29 isolates as T. asahii. The identity of the remaining
      four isolates was established as Trichosporon asteroides by direct DNA sequencing
      of the internally transcribed spacer (ITS)-1 and ITS-2 regions in the rRNA gene
      fragment amplified by PCR using panfungal primers. Fingerprinting carried out by
      randomly amplified polymorphic DNA analysis showed genotypic heterogeneity among
      the 25 T. asahii and four T. asteroides isolates. These data suggest that T.
      asahii is the major species associated with clinical specimens in Kuwait.

PMID- 15947429
TI  - Ibogaine reduces organ colonization in murine systemic and gastrointestinal
      Candida albicans infections.
AB  - In the present study the effect of the indole alkaloid ibogaine on the in vitro
      lipolytic activity and adherence to epithelial cells of Candida albicans was
      investigated. The substance was administered intraperitoneally at a dose of 5 mg
      kg(-1) day(-1) in mice with disseminated and gastrointestinal C. albicans
      infections. Ibogaine significantly decreased the rate of mortality and the number
      of C. albicans c.f.u. recovered from the kidney, liver and spleen. Ibogaine
      interfered with the early stages of both disseminated and gastrointestinal C.
      albicans infections but did not reduce the number of C. albicans c.f.u. in the
      organs at the late phase of infections. The development of a specific immune
      response was not influenced by ibogaine, since the delayed-type hypersensitivity
      reaction to C. albicans and the production of interferon (IFN)-gamma were similar
      in control and ibogaine-treated mice. The combined use of amphotericin B plus
      ibogaine in the treatment of mice with gastrointestinal infection reduced organ
      colonization more strongly than each substance alone.

PMID- 15947430
TI  - Widespread clone of Burkholderia cenocepacia in cystic fibrosis patients in the
      Czech Republic.
AB  - The morbidity and mortality rates in patients with cystic fibrosis (CF) are
      significantly affected by infections with Burkholderia cepacia complex. In a
      Czech CF Centre, the prevalence of the infection reached up to 30 %, with the
      majority of patients found to be infected with Burkholderia cenocepacia (formerly
      genomovar III of the Burkholderia cepacia complex). Since B. cenocepacia is
      associated with patient-to-patient transmission and epidemic outbreaks among CF
      patients, this study sought to examine the epidemiological relatedness between
      the Czech isolates belonging to the genomovar-homogeneous group. Eighty-three
      clinical isolates recovered from 67 CF patients were analysed using a random
      amplified polymorphic DNA (RAPD) assay and macrorestriction typing (SpeI and
      XbaI) followed by PFGE. A single predominant banding pattern shared by multiple
      isolates was detected, although SpeI-generated PFGE results yielded a higher rate
      of inter-pattern variability in comparison to the more uniform RAPD and XbaI
      generated PFGE results for this clone. Both typing systems also showed that only
      three out of 67 patients harboured strains distinct from the major strain type.
      The dominant clone was characterized by PCR positivity for the B. cepacia
      epidemic strain marker, PCR negativity for the cable pilin subunit gene and close
      genetic relatedness to the epidemic strain of RAPD 01 type previously identified
      in Canada.

PMID- 15947431
TI  - Longitudinal study of dental caries incidence associated with Streptococcus
      mutans and Streptococcus sobrinus in pre-school children.
AB  - Streptococcus mutans and Streptococcus sobrinus are known to be associated with
      the development of dental caries. In this study these bacteria were detected in
      pre-school children (each with primary dentition, age range 3-5 years, n = 60)
      using a PCR method, and then their presence was compared with the incidence of
      dental caries over a 1-year period. Plaque samples were collected from all
      erupted tooth sites using a sterile toothbrush. Dental examinations at the
      beginning of the study (baseline) and after 1 year were also performed to
      determine decayed, missing, filled teeth (dmft) scores using WHO caries
      diagnostic criteria. The prevalences of S. mutans and S. sobrinus across all the
      subjects were 61.7% and 56.6%, respectively; 13 subjects (21.7%) were positive
      for S. mutans alone, 10 (16.6%) were positive for S. sobrinus alone and 24
      (40.0%) were positive for both S. mutans and S. sobrinus, whereas 13 (21.7%) were
      negative for both S. mutans and S. sobrinus. dmft scores of subjects positive for
      both S. mutans and S. sobrinus at baseline and after 1 year were significantly
      higher than of those positive for S. mutans alone at the same stages (P < 0.01
      and P < 0.001, respectively). The caries incremental increase was also
      significantly greater in those with both bacteria detected (P < 0.05). Our
      results indicate that pre-school children harbouring both S. mutans and S.
      sobrinus have a significantly higher incidence of dental caries than those with
      S. mutans alone.

PMID- 15947432
TI  - Microcolony formation: a novel biofilm model of Pseudomonas aeruginosa for the
      cystic fibrosis lung.
AB  - Pseudomonas aeruginosa colonizing the lung of cystic fibrosis patients is
      responsible for a decline in health and poor prognosis for these patients. Once
      established, growth of P. aeruginosa in microcolonies makes it very difficult to
      eradicate the organisms by antimicrobial treatment. An artificial sputum medium
      was developed to mimic growth of P. aeruginosa in the cystic fibrosis lung
      habitat and it was found that the organisms grew in tight microcolonies attached
      to sputum components. Several genes, such as algD, oprF and lasR but not fliC,
      were required for tight microcolony formation. Among the sputum components, amino
      acids, lecithin, DNA, salt and low iron were required for tight microcolony
      formation. Amino acids were also shown to be responsible for various other cystic
      fibrosis-specific phenotypes of P. aeruginosa, such as diversification of colony
      morphology, alterations in LPS structure and hyperexpression of OprF. Since the
      amino acid content of sputum is elevated in severe lung disease, it is suggested
      that the tight microcolony biofilm is maintained in these conditions and that
      they contribute to the vicious cycle of disease severity and failure to eradicate
      the organism. Thus, growth of P. aeruginosa in artificial sputum medium is an
      appropriate model of chronic lung colonization and may be useful for evaluating
      therapeutic procedures and studying antibiotic-resistance mechanisms.

PMID- 15947433
TI  - Chryseobacterium indologenes bacteraemia in a diabetic child.
AB  - Chryseobacterium indologenes is a non-fermentative Gram-negative bacillus that is
      a rare pathogen in humans. Its occurrence in diabetic children has not been
      previously reported. In this report, a case is described of C. indologenes
      bacteraemia possibly associated with the use of a peripheral venous catheter. A 2
      year-old boy with type I diabetes mellitus was admitted due to a coma caused by
      cerebral oedema and was successfully treated for his neurological condition but
      presented on the tenth day after admission with fever of 40 degrees C, agitation,
      restlessness, lack of appetite, somnolence and fatigue. His pulse rate was 90
      min(-1) and his respiratory rate was 20 min(-1). Laboratory studies revealed a
      white blood cell count of 4900 mm(-3) with 67% neutrophils and 27% lymphocytes.
      Two separate blood cultures yielded C. indologenes. Treatment with ceftriaxone
      was started before the culture results were obtained, and was continued after
      susceptibility test results were obtained. The patient became afebrile after 48
      h, and his general condition improved within 36 h. The infection did not recur.
      This is believed to be the third case of bacteraemia outside of Asia due to C.
      indologenes and the first in a diabetic child not otherwise immunocompromised.
      This case indicates that C. indologenes infection can occur in diabetic children
      without ventilator or central venous catheter and might be treated with a single
      agent after in vitro susceptibility tests have been performed.

PMID- 15947434
TI  - Discordant molecular characterization results in a Mycobacterium avium complex
      strain isolated from an AIDS patient.
AB  - This report describes an unusual strain of Mycobacterium avium complex isolated
      from the sputum of an immunocompromised AIDS patient, which did not react with
      the MAC probe of the BDProbe Tec system, but was identified as Mycobacterium
      intracellulare by 16S rRNA gene sequencing. Its PCR restriction-enzyme analysis
      pattern was compatible with an allelic variant of M. avium. It was
      scotochromogenic, slow-growing and phenotypically identified as Mycobacterium
      scrofulaceum. Its clinical significance is not certain.

PMID- 15947435
TI  - Fatal pulmonary infection in a leukaemic patient caused by Hormographiella
      aspergillata.
AB  - A case of autopsy-proven fungal pneumonia in a relapsed leukaemia patient is
      reported. The fungus Hormographiella aspergillata was cultured from two
      bronchoalveolar fluid samples and identified through morphological examination
      and ITS2 sequence analysis. In addition, galactomannan was detected in eight
      consecutive serum samples, which suggested a co-infection with Aspergillus
      species. The patient was treated with caspofungin.

PMID- 15947436
TI  - Demonstration by PCR and DNA sequencing of Corynebacterium pseudodiphtheriticum
      as a cause of joint infection and isolation of the same organism from a surface
      swab specimen from the patient.
AB  - A case of infectious arthritis following arthroscopy is described. Real-time PCR,
      using universal bacterial primers targeting the 16S rRNA gene, and subsequent DNA
      sequencing of the PCR product demonstrated the presence of DNA from
      Corynebacterium pseudodiphtheriticum in the synovial fluid from the affected
      knee. Culture from a surface swab from the site of purulent discharge from the
      knee was initially reported as growing normal skin microbiota. Knowing the result
      of the DNA analysis, the specimen was re-examined and a diphtheroid bacterium was
      isolated. The DNA sequence of the isolated bacterium was identical to that of the
      DNA in the joint. The isolated bacterium was tested for susceptibility to
      relevant antibiotics. Demonstration and identification of bacterial DNA by PCR
      and gene sequencing may not by itself give information on important
      characteristics such as susceptibility to antibiotics of the infecting bacterium.
      The present case illustrates that the results obtained by the method can be used
      to isolate the relevant bacterium in culture from other sites and thereby
      characterize it. It furthermore demonstrates that C. pseudodiphtheriticum can
      cause severe arthritis when inoculated into joints.

PMID- 15947441
TI  - Letter: collision-induced dissociation of peptide thioesters: influence of the
      peptide length on the fragmentation.
AB  - Five peptide thioesters of increasing length were fragmented under two processes,
      in-source and in- collision cell fragmentation, using an electrospray source
      coupled to a triple quadrupole. Comparison of their fragmentations was made in
      regard to the length. The two fragmentation conditions show that the peptide
      length has no influence on structural information and that the fragmentation
      efficiency is higher for the smallest peptides than for the longest. The
      particularity of these peptide thioesters consists on the neutral loss of
      ethanethiol. The absence of the a3 fragment ion and the presence of the (a3-17)
      ion on the CID mass spectra are noted.

PMID- 15947437
TI  - Structural analysis of the O-antigen of Francisella tularensis subspecies
      tularensis strain OSU 10.

PMID- 15947443
TI  - Multiple tandem mass spectrometry-based investigation of the behaviour of some
      thiazol-benzimidazolones and 2-benzimidazolylsulfanyl ethanones.
AB  - The behaviour in electrospray conditions of a series of thiazol-benzimidazolones
      and 2- benzimidazolylsulphanyl ethanones has been studied by means of multiple
      tandem mass spectrometry experiments. Even though the experimental conditions
      were the same, different behaviour is observed for the two classes of compounds.
      In the case of thiazol-benzimidazolones, the formation of a protonated complex
      with CH3OH employed as solvent is observed, but in the case of 2
      benzimidazolylsulphanyl ethanones the formation of MNa+ ions is privileged. This
      behaviour has been related to molecular structure. The collisionally-induced
      decompositions of MH+ ions have been rationalised in terms of the Stevenson
      Audier and even-electron rules, as well as on the basis of proton affinity data.
      Thus, protonated thiazol-benzimidazolones undergo facile loss of CO and a series
      of different decomposition pathways involving cleavage of the thiazolone ring
      that reflect the structure of the neutral fragments. In contrast, the
      decompositions of the protonated 2-benzimidazolylsulphanyl ethanones are mainly
      related to the piperazine moiety, suggesting that the protonation takes place on
      this substructural unit.

PMID- 15947445
TI  - Probing the stability and structure of metalloporphyrin complexes with basic
      peptides by mass spectrometry.
AB  - The stability and structure of non-covalent complexes of various peptides
      contatining basic amino acid residues (Arg, Lys) with metalloporphyrins were
      studied in a quadrupole ion trap mass spectrometer. The complexes of heme and
      three other metalloporphyrins with a variety of basic peptides and model systems
      were formed via electrospray ionization (ESI) and their stability was probed by
      energy-variable collision-induced dissociation (CID). A linear dependence for
      basic peptides and model compounds/metalloporphyrin complexes was observed in the
      plots of stability versus degrees of freedom and was used to evaluate relative
      bond strength. These results were then compared with previous data obtained for
      complexes of metalloporphyrins with His-containing peptides and peptides
      containing no basic amino acids. The binding strengths of Lys-containing peptide
      complexes in the gas phase was found to be almost as strong as that of Arg
      containing complexes. Both systems showed stronger binding than His- containing
      peptides studied previously. To probe the structure of Arg and Lys non-covalent
      complexes (charge solvation versus salt bridges), two techniques, CID and
      ionmolecule reactions, were used. CID experiments indicate that the gas-phase
      complexes are most likely formed by charge solvation of the central metal ion in
      the metalloporphyrin by basic side chains of Arg or Lys. Results from the
      ionmolecule reaction studies are consistent with the charge solvation structure
      as well.

PMID- 15947446
TI  - Fragmentation of trimethoprim and other compounds containing alkoxy-phenyl groups
      in electrospray ionisation tandem mass spectrometry.
AB  - This work describes electrospray ionisation tandem mass spectrometry studies of
      trimethoprim and a series of structurally similar compounds containing alkoxy
      phenyl groups; using accurate mass measurement to confirm the proposed
      fragmentations. Radical cations were observed in the spectra obtained for some of
      the compounds, as well as uncommon fragmentations showing losses of CH4 and C2H6,
      whereas other compounds showed the formation of even electron ions. Possible
      structures for the fragment ions have been proposed and explanations for the
      different types of fragmentations based on the structures of the compounds. In
      addition an alternate structure for a fragment ion previously reported for tandem
      mass spectrometry of trimethoprim has been proposed, based on accurate mass
      measurement.

PMID- 15947447
TI  - Comparison of A+T-rich oligonucleotides with and without self-complementary
      sequence using ion-pair reversed-phase high-performance liquid
      chromatography/tandem electrospray ionization mass spectrometry.
AB  - Both A+T-rich oligonucleotides with and without self-complementary sequences were
      analyzed using ion- pair reversed-phase liquid chromatography/electrospray
      ionization mass spectrometry (IP-RP-HPLC/ESI-MS) by tryethylammonium acetate
      (TEAA) and hexafluoroisopropanol (HFIP) buffer systems to study the
      characteristics of their retention behavior and electrospray ionization tandem
      mass spectrometry (ESI-MS/MS) response. The results indicated that the chain
      length had the same effect on the retention of A+T-rich oligonucleotides in both
      of TEAA and HFIP buffer systems but the sequence had a different impact on the
      retention in the two buffer systems. A+T- rich oligonucleotides with a self
      complementary sequence were much shorter than those without in the TEAA buffer
      system whereas a slight difference was observed in the HFIP buffer system.
      Similar total ion current (TIC) intensity was observed both in oligonucleotides
      with or without self-complementary sequence. The opposite trend of a change in
      the TIC intensities with increasing chain length were observed in both the TEAA
      and HFIP buffer systems. A lower charge state was predominant in the TEAA buffer
      system whereas a higher charge state was mainly distributed in the HFIP buffer
      system. The oligonucleotides without self-complementary sequences had a higher
      charge state than those with self-complementary sequences. A- and T- are more
      esily formed at a higher charge state whereas the sequence fragments will be
      formed more easily at a lower charge state in both A+T-rich oligonucleotides with
      and without self-complementary sequences.

PMID- 15947448
TI  - Identification of flavonoids and their glycosides by high-performance liquid
      chromatography with electrospray ionization mass spectrometry and with diode
      array ultraviolet detection.
AB  - Identification of flavonoids and flavonoid glycosides was carried out on Psidium
      guajava Linn leaves by means of high-performance liquid chromatography
      ultraviolet (HPLC-UV) analysis and HPLC mass spectrometry. By using HPLC-UV, two
      known phenolics (gallic acid and quercetin) and five newly reported ones
      (procatechuic acid, chlorogenic acid, caffeic acid, kaempferol and ferulic acid)
      were identified in alcohol guava leaf extract. Structural information about the
      compounds was obtained from the retention times, the UV spectra and mass spectra
      without the need to isolate the individual compounds. Two flavonoids (quercetin
      and kaempferol) and four flavonoid glycosides (three known components, quercetin
      3-O-alpha-L-arabinoside, quercetin 3-O-beta-D-glucoside and quercetin 3-O-beta-D
      galactoside, along with one novel compound, kaempferol-glycoside) and three other
      unknown compounds have been identified in the fractions.

PMID- 15947449
TI  - Electrospray ionization mass spectrometry of pyrimidine base-rubidium complexes.
AB  - Nucleobases and alkali metal cations, under electrospray ionisation conditions,
      tend to form the so-called magic number clusters (unusually stable clusters in
      comparison with the neighbouring ones). The effect of the ion source parameters,
      namely cone voltage and desolvation temperature and relative concentrations of
      thymine and RbCl on the [T5+Rb]+ ion abundance has been studied.

PMID- 15947450
TI  - Characterization of electrospray ionization mass spectrometry for N
      diisopropyloxyphosphoryl dipeptide methyl esters.
AB  - A systematic study of the fragmentation pattern of N-diisopropyloxyphosphoryl
      (DIPP) dipeptide methyl esters in an electrospray ionization (ESI) tandem mass
      spectrometry (MS/MS) was presented. A combination of accurate mass measurement
      and tandem mass spectrometry had been used to characterize the major fragment
      ions observed in the ESI mass spectrum. It was found that the alkali metal ions
      acted as a fixed charge site and expelled the DIPP group after transferring a
      proton to the amide nitrogen. For all the N-phosphoryl dipeptide methyl esters,
      under the activation of a metal ion, the rearrangement product ion at m/z 163 was
      observed and confirmed to be the sodium adduct of phosphoric acid mono-isopropyl
      esters (PAIE), via a specific five-membered penta-co-ordinated phosphorus
      intermediate. However, no rearrangement ion was observed when a beta-amino acid
      was at the N-terminal. This could be used to develop a novel method for
      differentiating isomeric compounds when either alpha- or beta-amino acid are at
      the N-terminus of peptides. From the [M+Na]+ ESI-MS/MS spectra of N-phosphoryl
      dipeptide methyl esters (DIPP Xaa1 Xaa2 OMe), the peaks corresponding to the
      [M+Na Xaa1 C3H6]+ were observed and explained. The [M+Na]+ ESI-MS/MS spectra of N
      phosphoryl dipeptide methyl esters with Phe located in the C-terminal, such as
      DIPPValPheOMe, DIPPLeuPheOMe, DIPPIlePheOMe, DIPPAlaPheOMe and DIPPPhePheOMe, had
      characteristic fragmentation. Two unusual gas-phase intramolecular rearrangement
      mechanisms were first proposed for this fragmentation. These rearrangements were
      not observed in dipeptide methyl ester analogs which did not contain the DIPP at
      the N-terminal, suggesting that this moiety was critical for the rearrangement.

PMID- 15947451
TI  - Mass spectral studies on synthetic analogs of organophosphorus toxin occurring in
      dinoflagellate algae.
AB  - A series of organophosphorus compounds related to PB-1 toxin [O,O-diphenyl N-
      cyclooctylphosphoramidate] occurring in dinoflagellate algae as fish toxin have
      been synthesized and subjected to mass spectral studies under electron
      ionization. The fragmentation pattern obtained for the compounds has been
      substantiated by performing tandem mass spectrometry experiments in product ion
      scan mode.

PMID- 15947452
TI  - Review: derivatization in mass spectrometry--5. Specific derivatization of
      monofunctional compounds.
AB  - The present paper is complementary to the foregoing reviews and describes some
      additional methods of the derivatization of particular functional groups mainly
      to enhance the structural information content of electron ionization and chemical
      ionization mass spectra. Derivatization approaches for the modification of
      unsaturated compounds, alcoholic, carboxylic, carbonyl, amine and other
      functional groups, are discussed. Derivatization for separation and quantitative
      determination of chiral enantiomeric compounds is also considered. Preliminary
      chemical and physicalchemical degradation for structure elucidation of high
      molecular weight compounds (biopolymers, synthetic polymers) is mentioned.
      Chemical aspects of derivatizations and characteristic mass spectral features of
      derivatives are described briefly. Some particular applications of chemical
      modification, in conjunction with mass spectral measurements for the analysis of
      various important bioorganic compounds and compounds in biological fluids, air,
      environmental etc., are considered.

PMID- 15947453
TI  - In vivo evidence that local cortisol production increases in the preovulatory
      follicle of the cow.
AB  - The aim of the present in vivo study was to monitor real-time fluctuations of
      cortisol (Cr) in the wall of preovulatory follicles using a microdialysis system
      (MDS) implanted in the theca layer as well as changes in ovarian venous plasma
      (OVP) and jugular venous plasma (JVP). Seven cows were superovulated using FSH
      and prostaglandin F2alpha injections. Dialysis capillary membranes were
      surgically implanted into the theca layer of mature follicles and connected to a
      microdialysis system. Fractions of the perfusates were collected from Day -1 (Day
      0=LH surge) to Day 3. No difference in the concentrations of Cr between JVP and
      OVP was detected throughout the experiment. Circulating concentrations of Cr
      ranged from 20 to 35 ng/ml 8 h after surgery in ovulatory and anovulatory cows.
      In five ovulatory cows, the Cr concentration decreased to basal levels (<10
      ng/ml) between 12 and 24 h after surgery, however, two anovulatory cows retained
      high Cr levels (>10 ng/ml) up to 42 h after surgery. There was a clear increase
      in the local concentration of Cr from 13.3+/-2.1 pg/ml at -24 h to 27.5+/-1.7
      pg/ml at 0 h (peak of the LH surge) within the wall of ovulatory follicles. This
      increase was not detected in anovulatory follicles. This transient increase in Cr
      occurred only in the follicle wall, but not in the OVP or JVP, indicating that
      the presence of a local regulatory mechanism for Cr production/conversion in
      ovulatory follicles, and this mechanism may modulate the inflammatory-like
      reaction induced by LH surge in the follicle wall. The present results
      demonstrate that the glucocorticoid environment in the follicular wall adjusts at
      the local level in bovine ovulatory follicles. This mechanism may protect
      follicles from the adverse effects of glucocorticoid, and it may prevent excess
      inflammatory reactions associated with ovulation by temporarily increasing local
      concentrations of glucocorticoid, thus forming an integral part of the regulatory
      mechanism in ovarian physiology.

PMID- 15947454
TI  - Maternal exposure to bisphenol a during late pregnancy resulted in an increase of
      Calbindin-D9k mRNA and protein in maternal and postnatal rat uteri.
AB  - It has been reported that Calbindin-D9k (CaBP-9k) is rapidly and strongly induced
      by environmental estrogenic compounds, possibly through estrogen receptors
      (ERalpha) in the uterus of mammals. CaBP-9k can be evaluated as an early gene
      marker for assaying estrogenic effects of putative environmental chemicals in the
      rat uterus. This study was undertaken to investigate CaBP-9k mRNA and protein
      expression in the postnatal rat uterus following maternal exposure to 17beta
      estradiol (E2) and bisphenol A (BPA) during the neonatal period. Treatment with a
      high dose of BPA (600 mg/kg body weight (BW) per day) resulted in a 3-fold
      increase in CaBP-9k mRNA expression for 3 days, while a single dose of E2 (40
      microg/kg BW per day) induced 2-fold increase of this gene in the maternal
      uterus. In an agreement with maternal CaBP-9k mRNA, postnatal CaBP-9k mRNA in the
      uterus increased 4-fold when treated with BPA (600 mg/kg BW per day). In
      addition, treatment with increasing concentrations of BPA resulted in significant
      increases in CaBP-9k protein in the maternal rat uterus. It is of interest that
      increasing doses of BPA induced a significant ERalpha mRNA increase in the
      postnatal uterus. Furthermore, immunohistochemistry revealed that treatment with
      BPA induced CaBP-9k protein in the maternal uterus. We demonstrated that maternal
      exposure to BPA during late pregnancy induced CaBP-9k mRNA and protein in
      maternal and postnatal rat uteri. These results suggest that rapid absorption and
      distribution of environmental estrogenic compounds occurs in maternal and
      neonatal rat uteri and these chemicals can easily pass though the placenta during
      pregnancy to affect postnatal reproductive functions.

PMID- 15947455
TI  - Production of a transgenic pig expressing human albumin and enhanced green
      fluorescent protein.
AB  - We introduced a fusion gene of human albumin and enhanced green fluorescent
      protein (EGFP) into porcine oocytes using the sperm vector method, and produced a
      piglet that showed clear expression of GFP in the hooves and skin. PCR and
      Southern blotting analysis of genomic DNA extracted from the piglet's tissues,
      including the liver, showed that the tissues carried the transgene. RT-PCR
      analysis demonstrated that both the human albumin and EGFP genes were expressed
      in the tissues. The fact that human albumin gene was integrated and expressed in
      the liver of the transgenic pig opened a way for us to achieve our goal, which
      was the use of transgenic pigs for the bioartificial liver support system.

PMID- 15947456
TI  - Risk factors and the economic impact of ovarian cysts on reproductive performance
      of dairy cows in Korea.
AB  - The objectives of this study were to determine the risk factors for development
      of postpartum ovarian cysts by evaluating several reproductive factors in
      individual cows, and to determine the economic impact of ovarian cysts on
      subsequent reproductive performance in dairy herds in Korea. The data, including
      cow parity, abnormal puerperium, endometritis, body condition score (BCS), and
      breeding status were collected from 634 cows in 9 dairy herds. We used logistic
      regression to evaluate the effects of these factors on ovarian cysts. A stepwise
      procedure, used to obtain the appropriate model with alpha=0.05, revealed that
      cow parity was the most important risk factor for ovarian cyst development within
      8 weeks postpartum, while development of endometritis and BCS loss>or=1 from the
      dry period to 8 weeks postpartum were the most important risk factors for ovarian
      cyst development beyond 8 weeks postpartum. The occurrence of ovarian cysts
      beyond 8 weeks postpartum prolonged (P<0.01) the mean intervals from calving to
      first service (27 days) and conception (77 days), and increased (P<0.05) the
      culling rate (7.8%), while ovarian cyst development within 8 weeks postpartum did
      not affect (P>0.05) the mean intervals from calving to first service and
      conception or the culling rate. The economic loss resulting from the occurrence
      of ovarian cysts was estimated at approximately 823,996 won ($687) due to effects
      on the cost of nutrition, average growth of calves, labor and medical costs, and
      culling. These results suggest that cow parity is correlated with the development
      of ovarian cysts within 8 weeks postpartum, and endometritis and BCS loss>or=1
      from the dry period to 8 weeks postpartum are correlated with the development of
      ovarian cysts after 8 weeks postpartum, which decreases reproductive performance
      and results in economic loss in dairy herds in Korea.

PMID- 15947457
TI  - Seasonal influence on testicular function of male raccoons, Procyon lotor.
AB  - In order to clarify the breeding capability of male raccoons in Japan, the testes
      of raccoons, a nuisance animal, collected in Kanagawa Prefecture and Hokkaido
      were histologically inspected. Furthermore, testosterone concentrations in their
      blood were measured. The testosterone concentrations increased in winter and the
      diameter of seminiferous tubules and the spermatogenetic score decreased in
      summer for the animals captured in Kanagawa Prefecture. For the animals captured
      in Hokkaido, the diameter of seminiferous tubules did not change and the decrease
      of the spermatogenetic score in summer was slight. As the above results show,
      there is a breeding season in male raccoons in Japan, and the reduction of
      testicular function in summer was greater in animals captured in Kanagawa
      Prefecture than in animals captured in Hokkaido.

PMID- 15947458
TI  - Comparison of follicular and oocyte development and reproductive hormone
      secretion during the ovulatory period in Hungarian native breed, Mangalica, and
      Landrace gilts.
AB  - Only a very small amount of physiological data is available about the low
      fertility (mean litter size is 5.7+/-0.8) of Hungarian native breed, Mangalica
      (M), sows. The aim of the present paper is to reveal the differences in
      preovulatory follicle development and intrafollicular oocyte maturation between M
      and Landrace (L) gilts, with special reference to the peri- and postovulatory
      secretion and peripheral concentrations of estradiol-17beta (E2), progesterone
      (P4), and luteinizing hormone (LH). The number of preovulatory follicles was
      6.8+/-1.4 and 19.6+/-6.6 in M and L gilts, respectively. A lower degree of
      cumulus expansion and a lower percentage of mature oocytes (TI/M II) was noted in
      M. Higher LH and E2 peak levels, a longer E2 to LH peak interval, and lower
      embryo survival was confirmed. Interestingly, despite the lower number of corpora
      lutea, a higher peripheral blood level of P4 was shown in M than in L gilts. Both
      diminished follicular development and protracted oocyte maturation may be
      involved in low fecundity in M, and the present findings may explain these
      reproductive phenomena.

PMID- 15947459
TI  - Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues
      derived from different adult human CD34-negative progenitor cell clones.
AB  - Adult mesenchymal stem cells with multilineage differentiation potentially exist
      in the bone marrow, but have also been isolated from the peripheral blood. The
      differentiation of stem cells after leaving their niches depends predominately on
      the local milieu and its new microenvironment, and is facilitated by soluble
      factors but also by the close cell-cell interaction in a three-dimensional tissue
      or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from
      human bone marrow and peripheral blood and generated monoclonal cell populations
      after immortalization with the SV40 large T-antigen. The cultivation of those
      adult stem cell clones in an especially designed in vitro environment, including
      self-constructed glass capillaries with defined growth conditions, leads to the
      spontaneous establishment of pleomorphic three-dimensional cell aggregates
      (spheroids) from the monoclonal cell population, which consist of cells with an
      osteoblast phenotype and areas of mineralization along with well-vascularized
      tissue areas. Modifications of the culture conditions favored areas of bone-like
      calcifications. After the transplantation of the at least partly mineralized
      human spheroids into different murine soft tissue sites but also a dorsal
      skinfold chamber, no further bone formation could be observed, but angiogenesis
      and neovessel formation prevailed instead, enabling the transplanted cells and
      cell aggregates to survive. This study provides evidence that even monoclonal
      adult human CD34-negative stem cells from the bone marrow as well as peripheral
      blood can potentially differentiate into different mesenchymal tissues depending
      on the local milieu and responding to the needs within the microenvironment.

PMID- 15947460
TI  - Expression of the CD44 receptor in the blood vessel system: an experimental study
      in rat.
AB  - The CD44 receptor is a transmembrane glycoprotein expressed on a variety of cells
      like endothelial, epithelial and smooth muscle cells. This molecule has many
      important functions, e.g. in cell-cell and cell-matrix interactions and signal
      transduction. The main ligand for CD44 is hyaluronan (HYA). HYA is a
      glycosaminoglycan with structural and cell biological properties. The
      localization of HYA in the vessel wall of arteries and veins in the healthy adult
      and newborn rat has been described earlier. In this study the occurrence of the
      CD44 receptor was investigated in the same vessels and compared to the
      localization of HYA. Both CD44 and its ligand showed an increased expression in
      the vessel wall of newborn rats compared to that of adult rats. Although HYA is
      abundant in the adventitia of adult rats, virtually no expression of CD44 was
      observed. Our results indicate that the CD44 receptor expression is increased
      during the stage of maturation of the vessel tree whereas the CD44 receptor is
      less needed by HYA in the healthy vessel wall.

PMID- 15947461
TI  - Concerted upregulation of CLP36 and smooth muscle actin protein expression in
      human endometrium during decidualization.
AB  - The human endometrium prepares for implantation of the blastocyst by
      reorganization of its whole cellular network. Endometrial stroma cells change
      their phenotype starting around the 23rd day of the menstrual cycle. These
      predecidual stroma cells first appear next to spiral arteries, and after
      implantation these cells further differentiate into decidual stroma cells. The
      phenotypical changes in these cells during decidualization are characterized by
      distinct changes in the actin filaments and filament-related proteins such as
      alpha-actinin. The carboxy-terminal LIM domain protein with a molecular weight of
      36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with
      contractile actin filaments and to bind to alpha-actinin supporting a role for
      CLP36 in cytoskeletal reorganization and signal transduction by binding to
      signaling proteins. The expression patterns of CLP36, alpha-actinin and actin
      were studied in endometrial stroma cells from different stages of the menstrual
      cycle and in decidual stroma cells from the 6th week of gestation until the end
      of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal
      and glandular epithelium but not in endometrial stroma cells. During
      decidualization and throughout pregnancy, a parallel upregulation of CLP36 and
      smooth muscle actin, an early marker of decidualization in the baboon, was
      observed in endometrial decidual cells. Since both proteins maintain a high
      expression level throughout pregnancy, a role of both proteins is suggested in
      the stabilization of the cytoskeleton of these cells that come into close contact
      with invading trophoblast cells.

PMID- 15947462
TI  - Novel metal clusters isolated from blood are lethal to cancer cells.
AB  - Unfolding and subsequent aggregation of proteins is a common phenomenon that is
      linked to many human disorders. Misfolded hemoglobin is generally manifested in
      various autoimmune, infectious and inherited diseases. We isolated micrometer and
      submicrometer particles, termed proteons, from human and animal blood. Proteons
      lack nucleic acids but contain two major polypeptide populations with homology to
      the hemoglobin alpha-chain. Proteons form by reversible seeded aggregation of
      proteins around proteon nucleating centers (PNCs). PNCs are comprised of 1- to 2
      nm metallic nanoclusters containing 40-300 atoms. Each milliliter of human blood
      contained approximately 7 x 10(13) PNCs and approximately 3 x 10(8) proteons.
      Exposure of isolated blood plasma to elevated temperatures increased the number
      of proteons. When an aliquot of this heated plasma was introduced into untreated
      plasma that was subsequently heated, the number of proteons further increased,
      reaching a maximum after a total of three such iterations. Small concentrations
      of PNCs were lethal to cultured cancer cells, whereas noncancerous cells were
      much less affected.

PMID- 15947463
TI  - Hamstring muscles: architecture and innervation.
AB  - Knowledge of the anatomical organization of the hamstring muscles is necessary to
      understand their functions, and to assist in the development of accurate clinical
      and biomechanical models. The hamstring muscles were examined by dissection in
      six embalmed human lower limbs with the purpose of clarifying their gross
      morphology. In addition to obtaining evidence for or against anatomical
      partitioning (as based on muscle architecture and pattern of innervation), data
      pertaining to architectural parameters such as fascicular length, volume,
      physiological cross-sectional area, and tendon length were collected. For each
      muscle, relatively consistent patterns of innervation were identified between
      specimens, and each was unique with respect to anatomical organization. On the
      basis of muscle architecture, three regions were identified within
      semimembranosus. However, this was not completely congruent with the pattern of
      innervation, as a primary nerve branch supplied only two regions, with the third
      region receiving a secondary branch. Semitendinosus comprised two distinct
      partitions arranged in series that were divided by a tendinous inscription. A
      singular muscle nerve or a primary nerve branch innervated each partition. In the
      biceps femoris long head the two regions were supplied via a primary nerve branch
      which divided into two primary branches or split into a series of branches. Being
      the only muscle to cross a single joint, biceps femoris short head consisted of
      two distinct regions demarcated by fiber direction, with each innervated by a
      separate muscle nerve. Architecturally, each muscle differed with respect to
      parameters such as physiological cross-sectional area, fascicular length and
      volume, but generally all partitions within an individual muscle were similar in
      fascicular length. The long proximal and distal tendons of these muscles extended
      into the muscle bellies thereby forming elongated musculotendinous junctions.

PMID- 15947464
TI  - Effects of interferon-beta 1a on the hypothalamic-pituitary-adrenal axis,
      leukocyte distribution and mood states in multiple sclerosis patients: results of
      a 1-year follow-up study.
AB  - Acute interferon-beta (IFN-beta) administration transiently activates the
      hypothalamic-pituitary-adrenal (HPA) axis, increases granulocytes, and reduces
      lymphocytes in peripheral blood. To test whether these effects are still present
      after long-term treatment, 13 patients with relapsing-remitting multiple
      sclerosis were analyzed at baseline, and 1, 2, 4, and 8 h after IFN-beta 1a
      injection at two occasions: at the initial administration and after 1 year of
      continuous treatment. Long-term treatment reduced the responsiveness of the HPA
      axis to the injection, and abolished the distributional changes in leukocyte
      numbers. One-year treatment with IFN-beta 1a did not induce mood alterations as
      assessed by the Profile of Mood States. These results suggest that long-term IFN
      beta therapy has a profound impact on leukocyte distribution and the
      neuroendocrine response to the drug.

PMID- 15947465
TI  - An introduction to human biophoton emission.
AB  - BACKGROUND: Biophoton emission is the spontaneous emission of ultraweak light
      emanating from all living systems, including man. The emission is linked to the
      endogenous production of excited states within the living system. The detection
      and characterisation of human biophoton emission has led to suggestions that it
      has potential future applications in medicine. OBJECTIVES: An overview is
      presented of studies on ultraweak photon emission (UPE, biophotons) from the
      human whole body. METHODS: Electronic searches of Medline, PsychLit, PubMed and
      references lists of relevant review articles and books were used to establish the
      literature database. Articles were then analysed for their main experimental
      setup and results. RESULTS: The, mostly, single case studies have resulted in a
      collection of observations. The collection presents information on the following
      fields of research: (1) influence of biological rhythms, age, and gender on
      emission, (2) the intensity of emission and its left-right symmetry in health and
      disease, (3) emission from the perspective of Traditional Chinese and Korean
      Medicine, (4) emission in different consciousness studies, (5) procedures for
      analysis of the photon signal from hands, (6) detection of peroxidative processes
      in the skin. Of each article the main findings are presented in a qualitative
      manner, quantitative data are presented where useful, and the technological or
      methodological limitations are discussed. CONCLUSION: Photon emission recording
      techniques have reached a stage that allows resolution of the signal in time and
      space. The published material is presented and includes aspects like spatial
      resolution of intensity, its relation to health and disease, the aspect of
      colour, and methods for analysis of the photon signal. The limited number of
      studies only allows first conclusions about the implications and significance of
      biophotons in relation to health and disease, or to mental states, or
      acupuncture. However, with the present data we consider that further research in
      the field is justified.

PMID- 15947466
TI  - Spontaneous ultraweak photon emission from biological systems and the endogenous
      light field.
AB  - Still one of the most astonishing biological electromagnetic phenomena is the
      ultraweak photon emission (UPE) from living systems. Organisms and tissues
      spontaneously emit measurable intensities of light, i.e. photons in the visible
      part of the electromagnetic spectrum (380-780 nm), in the range from 1 to 1,000
      photons x s-1 x cm-2, depending on their condition and vitality. It is important
      not to confuse UPE from living systems with other biogenic light emitting
      processes such as bioluminescence or chemiluminescence. This article examines
      with basic considerations from physics on the quantum nature of photons the
      empirical phenomenon of UPE. This leads to the description of the non-thermal
      origin of this radiation. This is in good correspondence with the modern
      understanding of life phenomena as dissipative processes far from thermodynamic
      equilibrium. UPE also supports the understanding of life sustaining processes as
      basically driven by electromagnetic fields. The basic features of UPE, like
      intensity and spectral distribution, are known in principle for many experimental
      situations. The UPE of human leukocytes contributes to an endogenous light field
      of about 1011 photons x s-1 which can be influenced by certain factors. Further
      research is needed to reveal the statistical properties of UPE and in consequence
      to answer questions about the underlying mechanics of the biological system. In
      principle, statistical properties of UPE allow to reconstruct phase-space
      dynamics of the light emitting structures. Many open questions remain until a
      proper understanding of the electromagnetic interaction of the human organism can
      be achieved: which structures act as receptors and emitters for electromagnetic
      radiation? How is electromagnetic information received and processed within
      cells?

PMID- 15947467
TI  - Photon emission from perturbed and dying organisms: biomedical perspectives.
AB  - Living systems spontaneously emit ultraweak light (ultraweak photon emission,
      UPE) during the process of metabolic reactions associated with the normal
      physiological state. Stress factors and pathological states change parameters of
      that emission, such as intensity, yield, temporal, statistical and spectral
      characteristics. Thus, properties of UPE are inherently associated with and
      derived from biochemical and biophysical excitation processes. UPE can be
      considered as a holistic expression of the perturbation of the physiological
      state of the bio-system and may carry information on the bioenergetics, kinetics
      and character of biochemical and physiological processes, functioning of the
      regulatory feedback systems and the degree of perturbation by internal and
      external factors. This article presents an overview of the fundamentals of UPE
      and its relation to physiological processes.

PMID- 15947468
TI  - Multi-site recording and spectral analysis of spontaneous photon emission from
      human body.
AB  - BACKGROUND: In the past years, research on ultraweak photon emission (UPE) from
      human body has increased for isolated cells and tissues. However, there are only
      limited data on UPE from the whole body, in particular from the hands. OBJECTIVE:
      To describe a protocol for the management of subjects that (1) avoids
      interference with light-induced longterm delayed luminescence, and (2) includes
      the time slots for recording photon emission. MATERIAL AND METHODS: The protocol
      was utilised for multi-site recording of 4 subjects at different times of the day
      and different seasons, and for one subject to complete spectral analysis of
      emission from different body locations. An especially selected low-noise end
      window photomultiplier was utilised for the detection of ultraviolet / visible
      light (200-650 nm) photon emission. For multi-site recording it was manipulated
      in three directions in a darkroom with a very low count rate. A series of cut-off
      filters was used for spectral analysis of UPE. 29 body sites were selected such
      that the distribution in UPE could be studied as right-left symmetry, dorsal
      ventral symmetry, and the ratio between the central body part and extremities.
      RESULTS: Generally, the fluctuation in photon counts over the body was lower in
      the morning than in the afternoon. The thorax-abdomen region emitted lowest and
      most constantly. The upper extremities and the head region emitted most and
      increasingly over the day. Spectral analysis of low, intermediate and high
      emission from the superior frontal part of the right leg, the forehead and the
      palms in the sensitivity range of the photomultiplier showed the major
      spontaneous emission at 470-570 nm. The central palm area of hand emission showed
      a larger contribution of the 420-470 nm range in the spectrum of spontaneous
      emission from the hand in autumn/winter. The spectrum of delayed luminescence
      from the hand showed major emission in the same range as spontaneous emission.
      CONCLUSION: Examples of multi-site UPE recordings and spectral analysis revealed
      individual patterns and dynamics of spontaneous UPE over the body, and spectral
      differences over the body. The spectral data suggest that measurements might well
      provide quantitative data on the individual pattern of peroxidative and anti
      oxidative processes in vivo. We expect that the measurements provide
      physiological information that can be useful in clinical examination.

PMID- 15947469
TI  - Sertoli cell tumor causing prepubertal gynecomastia in a boy with peutz-jeghers
      syndrome: the outcome of 1-year treatment with the aromatase inhibitor
      testolactone.
AB  - Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by benign
      intestinal hamartomatous polyps and mucocutaneous pigmentation, and with an
      increased risk for intestinal and extra-intestinal neoplasms. Sertoli cell tumors
      in boys with PJS have been increasingly recognized as a cause of prepubertal
      gynecomastia. However, an association between nephrocalcinosis and PJS has not
      been reported before. We report on a 7.25-year-old boy with PJS, bilateral
      gynecomastia, Sertoli cell tumor and nephrocalcinosis, and present the outcome of
      1-year treatment with the aromatase inhibitor testolactone. The patient presented
      with bilateral breast and testis enlargement, and mucocutaneous pigmentation.
      Testicular ultrasound revealed parenchymal multiple microcalcifications.
      Histopathological examination was consistent with Sertoli cell tumors.
      Nephrocalcinosis due to idiopathic renal hypercalciuria was also detected. The
      aromatase inhibitor testolactone was begun in an attempt to prevent acceleration
      in skeletal maturation. One-year treatment with testolactone reduced the breast
      base diameter from 7 to 3 cm, and bone age advanced 1.2 years during this period.
      Our case demonstrates that waiting for the effect of aromatase inhibitors on
      gynecomastia before making a decision for mastectomy may be a reasonable option.
      We also consider that the association between PJS and nephrocalcinosis may be a
      coincidence.

PMID- 15947470
TI  - Can we predict or avoid the allergenic potential of genetically modified
      organisms?

PMID- 15947471
TI  - Assessing genetically modified crops to minimize the risk of increased food
      allergy: a review.
AB  - The first genetically modified (GM) crops approved for food use (tomato and
      soybean) were evaluated for safety by the United States Food and Drug
      Administration prior to commercial production. Among other factors, those
      products and all additional GM crops that have been grown commercially have been
      evaluated for potential increases in allergenic properties using methods that are
      consistent with the current understanding of food allergens and knowledge
      regarding the prediction of allergenic activity. Although there have been
      refinements, the key aspects of the evaluation have not changed. The allergenic
      properties of the gene donor and the host (recipient) organisms are considered in
      determining the appropriate testing strategy. The amino acid sequence of the
      encoded protein is compared to all known allergens to determine whether the
      protein is a known allergen or is sufficiently similar to any known allergen to
      indicate an increased probability of allergic cross-reactivity. Stability of the
      protein in the presence of acid with the stomach protease pepsin is tested as a
      risk factor for food allergenicity. In vitro or in vivo human IgE binding are
      tested when appropriate, if the gene donor is an allergen or the sequence of the
      protein is similar to an allergen. Serum donors and skin test subjects are
      selected based on their proven allergic responses to the gene donor or to
      material containing the allergen that was matched in sequence. While some
      scientists and regulators have suggested using animal models, performing broadly
      targeted serum IgE testing or extensive pre- or post-market clinical tests,
      current evidence does not support these tests as being predictive or practical.
      Based on the evidence to date, the current assessment process has worked well to
      prevent the unintended introduction of allergens in commercial GM crops.

PMID- 15947472
TI  - Suggestions for the assessment of the allergenic potential of genetically
      modified organisms.
AB  - The prevalence of allergic diseases has been increasing continuously and,
      accordingly, there is a great desire to evaluate the allergenic potential of
      components in our daily environment (e.g., food). Although there is almost no
      scientific evidence that genetically modified organisms (GMOs) exhibit increased
      allergenicity compared with the corresponding wild type significant concerns have
      been raised regarding this matter. In principle, it is possible that the
      allergenic potential of GMOs may be increased due to the introduction of
      potential foreign allergens, to potentially upregulated expression of allergenic
      components caused by the modification of the wild type organism or to different
      means of exposure. According to the current practice, the proteins to be
      introduced into a GMO are evaluated for their physiochemical properties, sequence
      homology with known allergens and occasionally regarding their allergenic
      activity. We discuss why these current rules and procedures cannot predict or
      exclude the allergenicity of a given GMO with certainty. As an alternative we
      suggest to improve the current evaluation by an experimental comparison of the
      wild-type organism with the whole GMO regarding their potential to elicit
      reactions in allergic individuals and to induce de novo sensitizations. We also
      recommend that the suggested assessment procedures be equally applied to GMOs as
      well as to natural cultivars in order to establish effective measures for allergy
      prevention.

PMID- 15947473
TI  - Sublingual immunotherapy for allergic rhinoconjunctivitis--the seeming and the
      real.
AB  - BACKGROUND: Subcutaneous specific immunotherapy (SIT) has been shown to be a
      causal treatment with long-term efficacy for allergic rhinoconjunctivitis and
      asthma, and a preventive measure against the development of asthma and new
      sensitizations. As it is associated with several inconveniences and serious side
      effects, sublingual immunotherapy (SLIT) has been developed to evade these
      problems. METHODS: The present review of previously published studies on allergic
      rhinoconjunctivitis aimed to determine the efficacy of SLIT in comparison with
      subcutaneous treatment and to summarize long-term results of immunotherapy and
      its effects on the prevention and treatment of asthma and the prevention of new
      sensitizations. RESULTS: The effect of SLIT on allergic rhinoconjunctivitis is
      low to moderate, depends on the allergen used and is more pronounced in adults
      than in children, in whom a consistent effect has not been demonstrated. Direct
      comparison with SIT shows conflicting and inconsistent results. Detailed studies
      on the prevention of asthma and new sensitizations are not available. Consistent
      effects of asthma treatment on both symptom and medication scores and lung
      function have not been reported. A quantitative evaluation is not possible due to
      indistinct inclusion criteria and different outcome criteria. In summary,
      currently SLIT plays no significant role in the treatment of asthma, apart from
      children monosensitized to house dust mites in whom it may have low-moderate
      effects. Only one study deals with the long-term efficacy of SLIT, which
      demonstrated a persistent positive effect on asthma, whereas data on
      rhinoconjunctivitis are completely lacking. CONCLUSIONS: Primary and secondary
      targets of specific immunotherapy have not been answered satisfactorily for the
      sublingual route. To date, SLIT cannot be recommended as an adequate alternative
      to the subcutaneous form. Questions regarding the cumulative dose, duration of
      therapy and immunological mechanisms have also not been answered. The indication
      should thus be limited to adult patients with pollen-induced rhinoconjunctivitis
      being unable to perform SIT, e.g. due to significant side effects.

PMID- 15947474
TI  - Regulatory T cells induced by ultraviolet radiation.
AB  - Regulatory T cells belong to a subset of T lymphocytes which suppress immune
      reactions in an antigen-specific fashion. They play an important role in the
      prevention of autoimmune diseases. Ultraviolet (UV) radiation was also found to
      suppress the immune system in an antigen-specific fashion mediated by UV-induced
      regulatory T cells. Induction of these cells by UV radiation is an active process
      which requires antigen presentation by UV-damaged but still viable Langerhans
      cells in the lymph nodes. UV-induced regulatory T cells have been recently
      characterized to express CD4 and CD25 and to release the immunosuppressive
      cytokine interleukin-10 upon activation. Once activated in an antigen-specific
      fashion, they suppress immune responses in a general fashion via the release of
      interleukin-10, a phenomenon called bystander suppression. Upon intravenous
      injection, UV-induced regulatory T cells primarily migrate into the lymph nodes,
      explaining why they preferentially suppress sensitization. Recently, the
      development of regulatory T cells was demonstrated in an experimental model of
      photopheresis, a therapeutic regimen which is used for the therapy of autoimmune
      diseases, transplant rejection and graft-versus-host disease. Further
      characterization of these cells will determine whether they can be applied
      therapeutically in the future with the ultimate aim to induce specific
      immunosuppression.

PMID- 15947475
TI  - Recombinant Der p 1 and Der f 1 with in vitro enzymatic activity to cleave human
      CD23, CD25 and alpha1-antitrypsin, and in vivo IgE-eliciting activity in mice.
AB  - BACKGROUND: The major house dust mite group 1 allergens Der p 1 and Der f 1 are
      the most potent indoor allergens. Der p 1 cleaves human cell surface molecules,
      the low-affinity IgE receptor (CD23/FcepsilonRII), the alpha-subunit of the IL-2
      receptor (CD25), and a protease inhibitor alpha1-antitrypsin, and in vitro and in
      vivo studies suggested the importance of its proteolytic activity in the
      pathogenesis of allergy. Recently, we established an efficient system to prepare
      correctly folded active recombinant Der p 1 and Der f 1 (Der p 1-N52Q and Der f 1
      N53Q) with similar molecular sizes, secondary structures and allergenicities as
      their natural types. To evaluate whether Der p 1-N52Q and Der f 1-N53Q are
      suitable for use in future in vitro and in vivo studies as alternatives to the
      natural types, we investigate their proteolytic activity to cleave the human
      proteins and IgE-eliciting activity in mice. METHODS: Proteolytic activities of
      Der p 1-N52Q and Der f 1-N53Q against a short peptide substrate, a collagen
      substrate Azocoll, human CD23 and CD25 expressed on the cells and human alpha1
      antitrypsin were analyzed by kinetic assays for proteolysis of the fluorogenic or
      colorimetric substrates, flow cytometry and sodium dodecyl sulphate
      polyacrylamide gel electrophoresis, respectively. Mice were intraperitoneally
      immunized with Der p 1-N52Q and Der f 1-N53Q adsorbed on Alum, and the serum IgE
      levels were measured by sandwich ELISA. RESULTS: Der p 1-N52Q and Der f 1-N53Q
      showed proteolytic specificities against the short peptide substrate, Azocoll,
      human cell surface CD23 and CD25 and human alpha1-antitrypsin, and elicited
      significant serum IgE levels in immunized mice. CONCLUSION: The recombinant
      forms, Der p 1-N52Q and Der f 1-N53Q, will be useful tools as alternatives to the
      natural Der p 1 and Der f 1 for various in vitro and in vivo analyses.

PMID- 15947476
TI  - Lipid transfer proteins and allergy to oranges.
AB  - BACKGROUND: Lipid transfer proteins (LTPs) are relevant fruit allergens, recently
      proposed as model plant food allergens. No citrus fruit allergen has been
      characterized to date. We sought to identify and isolate citrus fruit LTPs and to
      explore their relevance in orange allergy. METHODS: Twenty-seven patients,
      showing mainly oral allergy syndrome after orange ingestion, as well as positive
      prick responses and serum-specific IgE levels to orange, were selected. Natural
      orange and lemon LTPs, as well as a recombinant orange LTP isoform expressed in
      Pichia pastoris, were isolated by chromatographic methods and characterized by N
      terminal amino acid sequencing and matrix-assisted laser desorption/ionizaion
      mass spectrometry, and DNA sequencing of the corresponding cDNA in the case of
      the recombinant allergen. Specific IgE determination, immunodetection, ELISA
      inhibition assays and in vivo skin prick tests (SPTs) were performed with all
      three purified allergens and with the major peach LTP allergen, Pru p 3. RESULTS:
      The natural allergens purified from orange (nCit s 3) and lemon (nCit l 3) showed
      very similar N-terminal amino acid sequences (18 out of 20 identical residues),
      typical of LTPs, and molecular masses of 9,610 and 9,618 Da, respectively. The
      recombinant orange isoform (rCit s 3) expressed in P. pastoris (16 out of 20
      residues identical to its natural counterpart in the N-terminal region) presented
      92 amino acid residues and 9,463 Da, and 67% sequence identity with rPru p 3. Of
      the 27 sera analyzed, specific IgE to the purified allergens was found in 54% for
      nCit l 3, 48% for nCit s 3, 46% for rCit s 3 and 37% for rPru p 3. Positive SPT
      responses were obtained in 7 out of 26 patients tested for nCit s 3, 3 out of 8
      for nCit l 3 and 10 out of 26 for nPru p 3. ELISA-inhibition assays showed an
      equivalent IgE-binding pattern for the natural and recombinant orange LTPs, and
      IgE cross-reactivity among the purified orange, lemon and peach LTP allergens.
      CONCLUSIONS: Members of the LTP allergen family are involved in allergy to
      oranges, displaying positive in vitro and in vivo reactions in 30-50% of the
      patients studied. Both orange and lemon allergens show cross-reactivity with the
      major peach allergen Pru p 3.

PMID- 15947477
TI  - Effect of the cysteinyl leukotriene antagonist pranlukast on transendothelial
      migration of eosinophils.
AB  - BACKGROUND: Evidence shows that leukotriene receptor antagonist (LTRA) can cause
      a partial reduction of eosinophils in the asthmatic airway. Although cysteinyl
      leukotrienes (CysLTs) can regulate the development of eosinophilic inflammation,
      LTRA might modulate the eosinophilic response to other inflammatory molecules
      involved in allergic inflammation. Montelukast is an LTRA that inhibits
      eosinophil transendothelial migration (TEM) in response to platelet-activating
      factor (PAF). The present study evaluates whether pranlukast (an LTRA) modifies
      eosinophil TEM in response to chemoattractants including PAF and C-C chemokines.
      METHODS: Eosinophils isolated from the blood of healthy individuals were
      incubated with or without pranlukast. We then evaluated eosinophil transmigration
      across human umbilical vein endothelial cells in response to LTD(4), eotaxin,
      RANTES and PAF. RESULTS: Pranlukast did not modify the spontaneous transmigration
      of eosinophils (n = 5). As reported, eosinophil TEM was significantly augmented
      by 0.1 microM LTD(4) and this enhancement was blocked by 1 microM pranlukast (p <
      0.001; n = 6). On the other hand, pranlukast did not modify eosinophil
      transmigration in response to eotaxin, RANTES, or PAF (p > 0.1; n = 5).
      CONCLUSION: The inhibitory effect of pranlukast on eosinophil transmigration is
      highly specific for the CysLT1-dependent pathway.

PMID- 15947478
TI  - Association between neutrophilic and eosinophilic inflammation in patients with
      severe persistent asthma.
AB  - BACKGROUND: Eosinophils are generally recognized as effector cells in asthma.
      Recently, neutrophils have been suggested to contribute to the development of
      chronic severe asthma. The mechanisms by which neutrophils contribute to the
      pathophysiology of asthma remain to be elucidated; however, neutrophils may
      affect either accumulation or functional status of eosinophils via the generation
      of inflammatory mediators. The objective of this study was to evaluate whether
      neutrophilic inflammation is associated with eosinophilic inflammation in severe
      asthma. METHODS: Following the inhalation of hypertonic saline, induced sputum
      was obtained from 12 healthy controls, 10 mild persistent asthmatics who were
      treated with low-dose inhaled corticosteroids, and 8 severe persistent asthmatics
      who were treated with combinations of drugs including high-dose inhaled
      corticosteroids and oral prednisolone. Subsequently, differential inflammatory
      cell counts were evaluated. RESULTS: The percentage of eosinophils in induced
      sputum was significantly higher in patients who showed airway neutrophilia. In
      severe persistent asthmatics, the percentage of neutrophils was significantly
      correlated with the percentage of eosinophils in induced sputum. CONCLUSIONS: The
      results of the present study suggest that accumulated neutrophils may contribute
      to the development of eosinophilic inflammation in severe persistent asthmatics
      who were treated with oral and high-dose inhaled corticosteroids. This effect may
      contribute to the eventual manifestation of airway inflammation in severe asthma.

PMID- 15947479
TI  - RANTES and eotaxin enhance CD11b and CD18 expression on eosinophils from allergic
      patients with eosinophilia in the application of whole Blood flow cytometry
      analysis.
AB  - BACKGROUND: C-C chemokines and adhesion molecules expressed on eosinophils play
      an important role in the pathology of allergic inflammatory disease. C-C
      chemokines such as eotaxin or RANTES are involved in beta(2) integrin expression
      on purified eosinophils; so far we have no data on unpurified eosinophils in the
      peripheral blood. We measured beta(1) and beta(2) integrin activation after
      stimulation with eotaxin or RANTES in vitro using whole-blood flow-cytometric
      analysis. METHODS: Heparinized whole blood obtained from allergic patients with
      eosinophilia or normal subjects was diluted with the same volume of RPMI 1640,
      and then cells were incubated in the presence or absence of PMA/ionomycin or
      chemokines for 45 min at 37 degrees C. After hemolyzation with lysing solution,
      expression of CD11b, CD11a, CD18 and CD49d on eosinophils was measured using flow
      cytometry. RESULTS: The expression of CD11b, CD11a and CD18 in allergic patients
      was significantly higher than that in normal subjects. CD11b and CD18 expression
      showed a significant increase after stimulation with C-C chemokines, which was
      remarkable in allergic patients. CONCLUSION: Eosinophils in the blood of allergic
      patients exhibited a higher expression of beta(2) integrins and were more
      sensitive to RANTES and eotaxin than those of normal subjects.

PMID- 15947480
TI  - Leukotriene D4 induces production of transforming growth factor-beta1 by
      eosinophils.
AB  - Eosinophils may play an important role in the pathogenesis of airway remodeling
      in asthma through the production of various fibrogenic cytokines such as
      transforming growth factor-beta1 (TGF-beta1). Cysteinyl leukotrienes are also
      suggested to be involved in remodeling with their potential to induce
      proliferation of airway smooth muscle cells. Since massive eosinophil
      infiltration and the release of cysteinyl leukotrienes in airway secretions are
      often seen in asthma, we hypothesized that cysteinyl leukotrienes may be involved
      in airway remodeling through induction of TGF-beta1 from eosinophils. Peripheral
      blood eosinophils were cultured with leukotriene D(4) (LTD(4)) and/or interleukin
      5 (IL-5) or granulocyte colony-stimulating factor (GM-CSF) for 16 h and gene
      expression of TGF-beta1 was quantified with real-time PCR. A combination of
      LTD(4) and IL-5 or LTD(4) and GM-CSF synergistically induced TGF-beta1 expression
      in eosinophils although stimulation with single factor, LTD(4), IL-5 or GM-CSF
      did not induce the gene expression. LTD(4) also induced significant gene
      expression in eosinophils cultured in an intercellular adhesion molecule-1-coated
      plate. The results suggested that CysLTs stimulate eosinophils to induce TGF
      beta1 production in allergic inflammation where IL-5 and GM-CSF are abundant and
      may be involved in the pathogenesis of airway remodeling.

PMID- 15947481
TI  - The synthetic chemoattractant peptide WKYMVm induces superoxide production by
      human eosinophils via the phosphoinositide 3-kinase-mediated activation of
      ERK1/2.
AB  - BACKGROUND: Eosinophils play a key role in allergic inflammation and parasitic
      infections. The synthetic peptide, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), has been
      previously shown to activate eosinophils and thus to enhance respiratory burst
      through the formyl peptide receptors. OBJECTIVE: This study was undertaken to
      determine the intracellular signaling pathway involved in WKYMVm-stimulated
      superoxide production by human eosinophils. METHODS: Purified eosinophils from
      peripheral blood were stimulated with various concentrations (10(-3) to 10
      microM) of WKYMVm and the involvement of PI3-kinase and MAP kinases in WKYMVm
      triggered superoxide production was investigated using pharmacological
      inhibitors. RESULTS: WKYMVm-induced superoxide production by eosinophils was
      strongly inhibited by pretreatment with the PI3-kinase inhibitor LY294002. In
      addition, pretreatment with the ERK1/2 kinase inhibitor PD98059 resulted in
      marked inhibition of superoxide production induced by WKYMVm. Indeed, WKYMVm
      strongly induced phosphorylation of ERK1/2. The ERK1/2 activation by the peptide
      was transient and peaked after 2 min of stimulation. Furthermore, ERK1/2
      activation by WKYMVm was completely inhibited by pretreatment with the PI3-kinase
      inhibitor LY294002, but not by the PKC inhibitor Ro-31-8220. CONCLUSION: These
      results suggest that WKYMVm stimulates human eosinophils to induce superoxide
      production via a PI3-kinase-mediated ERK1/2 pathway.

PMID- 15947482
TI  - Differential role of an atypical protein kinase C, PKC zeta, in regulation of
      human eosinophil and neutrophil functions.
AB  - BACKGROUND: Protein kinase C (PKC) comprises a family of isoenzymes playing a key
      role in downstream signaling and cell functions. PKCs are grouped according to
      molecular structure and mode of activation: 'conventional' PKCs (alpha, betaI,
      betaII, gamma), 'novel' PKCs (delta, epsilon, mu, theta, eta), and 'atypical'
      PKCs (zeta, tau/lambda). Here we compared the influence of PKC zeta on the
      function of human eosinophils and neutrophils. METHODS: After pretreating the
      cells with a myristoylated specific PKC zeta inhibitor, a myristoylated PKC eta
      inhibitor, or bisindolylmaleimide I (Bis I; an inhibitor of conventional and
      novel PKCs), we examined N-formyl-methionyl-leucyl-phenylalanine (FMLP)- or 4
      phorbol 12-myristate 13-acetate (PMA)-evoked superoxide anion (O(2)(-))
      generation. Induced PKC translocation was characterized using confocal laser
      scanning microscopy. RESULTS: The PKC zeta inhibitor significantly blocked FMLP-
      or PMA-induced O(2)(-) generation by eosinophils. However, this inhibitor
      attenuated PMA- but not FMLP-induced O(2)(-) generation by neutrophils. In
      contrast, Bis I inhibited FMLP-induced O(2)(-) generation by eosinophils and
      neutrophils in a similar manner. The PKC eta inhibitor had no significant effect,
      since both cell types lack PKC eta; this confirmed specificity of PKC zeta
      inhibitor effects. Finally, the translocation of PKC zeta to the plasma membrane
      induced by FMLP in both eosinophils and neutrophils was started at 1 min while
      the translocation was maintained for 15 min in eosinophils but not in
      neutrophils. CONCLUSION: An atypical PKC, PKC zeta, regulates human eosinophil
      and neutrophil functions in a differential manner.

PMID- 15947483
TI  - NR4A orphan nuclear receptor family in peripheral blood eosinophils from patients
      with atopic dermatitis and apoptotic eosinophils in vitro.
AB  - To identify novel genes related to the clinical signs of atopic dermatitis (AD),
      differentially expressed genes were sought in peripheral blood eosinophils from
      both AD patients and healthy volunteers. RNA was prepared from eosinophils,
      expression of various genes was monitored using the Affymetrix GeneChip, and
      expression was quantified by real-time RT-PCR. Two genes, Nur77 and NOR1, members
      of NR4A orphan nuclear receptor family, were expressed at a significantly higher
      level in AD patients than in healthy volunteers. Expression of another gene in
      the NR4A receptor family, Nurr1, was also higher in AD patients than in healthy
      volunteers. When peripheral blood leukocytes from healthy volunteers were
      fractionated, NOR1 expression was highest in eosinophils, but expression of Nur77
      and Nurr1 genes was not eosinophil-specific. Extremely intense apoptosis was
      induced in both eosinophils and an eosinophil cell line, AML14.3D10, by treatment
      with antibody (Ab) to both CD30 and Fas. Rapid expression of the genes for the
      NR4A receptor family was observed with anti-CD30 Ab treatment but not with anti
      Fas Ab. The NR4A orphan nuclear receptor family gene expression and the
      subsequent eosinophil apoptosis were downregulated by the MAPK inhibitor, U0126.
      These results suggest that the expression of the NR4A receptor family genes
      through CD30 signaling may regulate eosinophil apoptosis in allergic conditions
      such as AD.

PMID- 15947485
TI  - Comparison of IL-17 production by helper T cells among atopic and nonatopic
      asthmatics and control subjects.
AB  - BACKGROUND: T cells, eosinophils, and neutrophils are strongly involved in the
      pathogenesis of bronchial asthma. Mechanisms that influence neutrophil
      accumulation and activation in asthma still remain relatively obscure. There is
      data indicating that IL-17 is produced by T cells and causes the release of
      neutrophil-mobilizing cytokines from airway epithelial cells, and that in this
      way it may regulate airway neutrophilia. METHODS: Peripheral blood mononuclear
      cells (PBMC) obtained from atopic asthmatics (AA), nonatopic asthmatics (NA), and
      normal control subjects (NC) were stimulated by immobilized anti-CD3 antibody
      (Ab) plus soluble anti-CD28 Ab or Dermatophagoidesfarinae (Df) extract. Df
      reactive T cell clones were established from PBMC of AA and cultured in the
      presence of various stimulants. The resulting supernatants were assayed for IL-2,
      IL-4, IL-5, IL-13, IL-17, and IFN-gamma by specific ELISAs. RESULTS: PBMC
      obtained from AA, NA, and NC all produced IL-17 upon immobilized anti-CD3 Ab plus
      soluble anti-CD28 Ab stimulation. IL-17 production in response to Df extract was
      significantly induced only in AA. The amount of IL-17 produced by T cell clones
      stimulated with immobilized anti-CD3 Ab plus soluble anti-CD28 Ab was negatively,
      but only weakly, correlated with that of IL-4, but not correlated with IL-2, IL
      5, IL-13, and IFN-gamma production. CONCLUSION: T cells producing IL-17 in
      response to Df antigen exist in the peripheral blood of the sensitized AA. IL-17
      production might be regulated by unique mechanisms different from those governing
      Th1 versus Th2 differentiation.

PMID- 15947484
TI  - Stat5a is essential for the proliferation and survival of murine mast cells.
AB  - The regulatory role of signal transducer and activator of transcription (Stat) 5a
      in the proliferation and survival of mast cells was determined using Stat5a
      deficient (Stat5a(-/-)) mice. First, although the mast cells in Stat5a(-/-) mice
      were morphologically indistinguishable from those in wild-type (WT) mice, the
      number of peritoneal mast cells was significantly decreased in Stat5a(-/-) mice
      as compared with that in WT mice. Furthermore, the interleukin-3 (IL-3)-dependent
      development of bone marrow-derived mast cells (BMMCs) was markedly decreased in
      Stat5a(-/-) mice. Second, IL-3-induced but not stem cell factor (SCF)-induced
      proliferation of BMMCs was significantly diminished in Stat5a(-/-) mice as
      compared with that in WT mice. Moreover, survival rates of both peritoneal mast
      cells and BMMCs were significantly decreased with increased apoptotic cells in
      Stat5a(-/-) mice as compared with those in WT mice. Finally, mRNA of Bcl-x(L) was
      induced after IL-3 stimulation in WT BMMCs but not in Stat5a(-/-) BMMCs, which
      may account for the accelerated apoptosis in Stat5a(-/-) mast cells. These
      results indicate that Stat5a plays an important role in mast cell development,
      proliferation, and survival.

PMID- 15947486
TI  - Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients.
AB  - BACKGROUND: Helper T cells and T cell cytokines play central roles in allergic
      disorders including bronchial asthma. We reported enhanced IL-5 production by
      peripheral blood T cells of asthmatic patients. A transcription factor, GATA-3,
      has been implicated in IL-5 gene expression. This study was undertaken to clarify
      the role of GATA-3 in the upregulation of IL-5 synthesis in asthmatic patients.
      METHOD: Peripheral CD4+ T cells were transfected with an IL-5 promoter reporter
      construct as well as its mutants in the presence or absence of a GATA-3
      expression vector. Messenger RNA expression level of GATA-3 in CD4+ T cells of
      asthmatic subjects was compared to that of healthy donors. RESULTS: IL-5 promoter
      activity in CD4+ T cells was enhanced by overexpression of GATA-3, whereas it was
      diminished by the introduction of mutations in the putative GATA-3 binding sites.
      The GATA-3 expression level in CD4+ T cells of asthmatic patients was equivalent
      to that of healthy controls. CONCLUSION: The expression level of GATA-3 may not
      be an essential factor to cause IL-5 hyperproduction in bronchial asthma, though
      GATA-3 is crucially involved in IL-5 gene transcription in human peripheral CD4+
      T cells.

PMID- 15947487
TI  - Effects of corticosteroid on the expression of thymus and activation-regulated
      chemokine in a murine model of allergic asthma.
AB  - BACKGROUND: Thymus and activation-regulated chemokine (TARC; CCL17) is a
      lymphocyte-directed CC chemokine that specifically attracts T-helper (Th) 2 cells
      positive for the CC chemokine receptor 4 (CCR4(+)). Corticosteroids reduce airway
      inflammation, as reflected by reduced numbers of eosinophils and T cells and
      reduced expression of cytokines. We investigated TARC production and the
      inhibitory effects of corticosteroids on TARC expression in a murine model of
      allergic asthma. METHODS: BALB/c mice were sensitized by intraperitoneal
      injection of ovalbumin (OVA) with alum. Once daily for 1 week, mice received
      injections of dexamethasone or 0.2 ml saline (control), then 1 h later inhaled
      aerosolized 1% OVA for 30 min. Mice were killed 24 h after OVA challenge for
      bronchoalveolar lavage and lung tissue examination. RESULTS: TARC was expressed
      mainly in the bronchial epithelial cells. Dexamethasone attenuated OVA-induced
      airway eosinophilia, lymphocyte infiltration, and airway hyperresponsiveness.
      Dexamethasone also decreased TARC production in the bronchoalveolar lavage fluid
      and decreased expression of TARC mRNA and TARC protein in lung tissue.
      CONCLUSIONS: The corticosteroid dexamethasone inhibits TARC production in a
      murine model of allergic asthma in vivo. The beneficial effect of corticosteroids
      in bronchial asthma is due in part to their direct inhibitory effects on TARC
      production.

PMID- 15947488
TI  - Infantile eczema at one month of age is associated with cord blood eosinophilia
      and subsequent development of atopic dermatitis and wheezing illness until two
      years of age.
AB  - BACKGROUND: Physiological and pathological skin eruptions are commonly
      encountered in neonates in our clinical practice. However, the types of skin
      eruptions that are associated with the subsequent development of atopic
      dermatitis and the mechanisms of these associations remain uncertain. METHODS: A
      total of 105 newborn babies with normal delivery were enrolled in this
      prospective cohort study. The cord blood eosinophil count was measured and the
      neonates were examined at 1 month of age and followed until 8 years of age.
      RESULTS: At 1 month of age, infantile eczema, seborrheic dermatitis, intertrigo
      and diaper dermatitis were diagnosed in a total of 29, 7, 14 and 24 neonates,
      respectively. No association was found among the prevalences of these eruptions.
      Neonates with infantile eczema had a significantly higher number and ratio of
      eosinophils in the cord blood (eosinophil count: 670.8 +/- 67.8 vs. 349.0 +/-
      30.3/microl, p < 0.0001; eosinophil ratio: 5.12 +/- 0.53 vs. 2.61 +/- 0.22%, p <
      0.0001, for the presence and the absence of infantile eczema, respectively). In
      contrast, no such tendency was found for any other skin eruptions. In neonates
      with infantile eczema at 1 month of age, the diagnosis of atopic dermatitis had
      been made significantly earlier and the prevalence of wheezing illness was
      significantly higher than in those without infantile eczema until 2 years of age.
      CONCLUSION: Infantile eczema, but not other skin eruptions, precedes the
      development of atopic dermatitis and wheezing illness during early infancy,
      presumably because of the activation of eosinophils before birth.

PMID- 15947489
TI  - Mechanism of the eosinophilic differentiation of HL-60 clone 15 cells induced by
      n-butyrate.
AB  - n-Butyrate is one of the most powerful chemical inducers of the differentiation
      of human eosinophilic leukemia HL-60 clone 15 cells into mature eosinophils. We
      have recently reported that the mechanism by which HL-60 clone 15 cells
      differentiate into eosinophils by n-butyrate is that n-butyrate continuously
      inhibits histone deacetylase activity as a histone deacetylase inhibitor,
      resulting in continuous acetylation of histones. In this review, we discuss roles
      of histone acetyltransferase, histone deacetylase and histone deacetylase
      inhibitors in the differentiation of HL-60 clone 15 cells into eosinophils.

PMID- 15947490
TI  - Depression and spinal cord injury.

PMID- 15947491
TI  - Depression following traumatic spinal cord injury.
AB  - OBJECTIVES: To describe the epidemiology of depression following traumatic spinal
      cord injury (SCI) and identify risk factors associated with depression. METHODS:
      This population-based cohort study followed individuals from date of SCI to 6
      years after injury. Administrative data from a Canadian province with a universal
      publicly funded health care system and centralized databases were used. A Cox
      proportional hazards model was developed to identify risk factors. RESULTS: Of
      201 patients with SCI, 58 (28.9%) were treated for depression. Individuals at
      highest risk were those with a pre-injury history of depression [hazard rate
      ratio (HRR) 1.6; 95% CI: 1.1-2.3], a history of substance abuse (HRR 1.6; 95% CI:
      1.2-2.3) or permanent neurological deficit (HRR 1.6; 95% CI: 1.2-2.1).
      CONCLUSION: Depression occurs commonly and early in persons who sustain an SCI.
      Both patient and injury factors are associated with the development of
      depression. These should be used to target patients for mental health assessment
      and services during initial hospitalization and following discharge into the
      community.

PMID- 15947492
TI  - Epidemiological survey of epilepsy in the primary school population in Buenos
      Aires.
AB  - BACKGROUND: Most studies carried out in Latin America have shown greater rates of
      epilepsy and generalized seizures than those observed in developed countries, in
      spite of lower numbers of patients receiving treatment. To date, studies in
      Argentina have been insufficient to establish true prevalence. OBJECTIVE: To
      determine the prevalence of epilepsy in primary school children in Buenos Aires,
      together with rates of different seizure types, treatments prescribed, diagnoses
      made and number of inadequate therapies administered, as well as the relationship
      between epilepsy and learning difficulties. DESIGN AND METHOD: A cross-sectional
      study was carried out on 10% of the entire primary school population of Buenos
      Aires through randomized, systematic, representative and conglomerate sampling of
      public and private school students. A total of 26,270 responses were received
      (83.1% of the population) to a specially designed questionnaire, with 96.4%
      sensitivity and 41.5% specificity, respectively. Interviews were conducted in all
      probable epilepsy cases as well as in a random sample of probable negative ones.
      RESULTS: Eighty-four children with epilepsy were detected (lifetime prevalence
      3.2 per thousand; active prevalence 2.6 per thousand), in whom generalized
      seizures predominated (57.1%). Ninety-three percent of cases diagnosed were
      currently under, or had previously received antiepileptic drug (AED) therapy.
      Almost 1% of the primary school population studied had a prior diagnosis and/or
      received AED for dysrhythmia or epilepsy. The percentage of grade repeaters in
      the general population and in children with epilepsy was 8.4 and 26.2%,
      respectively. CONCLUSIONS: (1) The prevalence of epilepsy in primary school
      children in Buenos Aires is similar to that reported for developed countries; (2)
      a slight prevalence for generalized seizures was observed; (3) 93% of cases
      received AEDs; (4) misdiagnoses and unnecessary treatments exceeded correct
      diagnoses and adequate therapy, and (5) disease presence and/or treatment were
      associated with poorer school performance.

PMID- 15947493
TI  - Association between impaired insulin sensitivity and stroke.
AB  - BACKGROUND: Prior research has indicated an association between insulin
      resistance and stroke; we sought to determine if this association persists after
      adjusting for stroke risk factors, including glycemic control. METHODS: We used
      data from the Third National Health and Nutrition Survey (1988-1994), including
      participants aged > or =40 years. We assessed insulin sensitivity using the
      homeostasis model assessment (HOMA): HOMA = (FPGSI x FPI)/22.5, where FPGSI
      refers to fasting plasma glucose (mmol/l) and FPI refers to fasting plasma
      insulin (microU/l). Increasing HOMA indicates decreasing insulin sensitivity. We
      used glycosylated hemoglobin (HbA1c) to measure glycemic control. Multivariable
      logistic regression analysis was used to identify factors that were independently
      associated with stroke. RESULTS: Among 3,844 participants, 168 (4%) reported a
      stroke history. Participants with stroke had lower insulin sensitivity than
      participants without stroke: HOMA mean +/- standard deviation, 4.0 +/- 4.0 vs.
      3.3 +/- 3.0; p = 0.022. HOMA was independently associated with stroke (odds ratio
      1.06, 95% CI: 1.01-1.12; adjusted for age, hypertension, myocardial infarction,
      claudication, activity, and HbA1c). The strength of the association between HOMA
      and stroke was similar to the association between claudication and stroke (index
      R(2): 0.0032 vs. 0.0036). CONCLUSIONS: Impaired insulin sensitivity is
      independently associated with stroke, even after adjustment for glycemic control.

PMID- 15947494
TI  - Underlying cause of death in demented and non-demented elderly Canadians.
AB  - This paper examines the associations between clinical dementia and underlying
      cause of death (UCD) in a population-based sample of seniors who took part in the
      Canadian Study of Health and Aging (CSHA). Cause-of-death data were obtained via
      death certificates for 2,924 of 2,982 deceased subjects. Among the decedents were
      823 clinically demented and 670 clinically non-demented participants. Using
      logistic regression we examined factors associated with a particular UCD in the
      overall group and also in the subgroup of demented seniors. Dementia was found to
      be associated with an increased risk of death from pneumonia. Both Alzheimer's
      disease and vascular dementia appear to decrease the risk of mortality from
      neoplasm. To our knowledge, this study is the first of its kind that combines a
      large, representative sample with thorough clinical assessment of cognitive
      status.

PMID- 15947495
TI  - The C3435T polymorphism of MDR1 and susceptibility to adult glioma.
AB  - INTRODUCTION: The multidrug resistance-1 (MDR1) gene encodes a pump that prevents
      potentially carcinogenic substances from crossing the blood-brain barrier. We
      compare adult glioma cases and controls for the C3435T polymorphism that has been
      associated with reduced MDR1 expression. METHODS: Adult glioma in the San
      Francisco Bay area and population-based controls were identified between 1991
      1994 and 1997-1999. Genotyped cases (n = 458) and controls (n = 528) were
      compared using logistic regression controlling for age, gender and ethnicity,
      with later stratification by ethnicity, gender and histology. RESULTS: With CC as
      the referent, the TT genotype was nonsignificantly less frequent among cases
      compared to controls (OR, 0.87; 95% CI: 0.6, 1.2). After stratification, only
      male glioblastoma was associated with TT genotype (OR, 0.51; 95% CI: 0.3, 1.0).
      CONCLUSIONS: Although the C3435T polymorphism does not appear to be associated
      with other types of glioma, we cannot rule out that this MDR1 polymorphism may be
      associated with glioblastoma among men.

PMID- 15947496
TI  - Simulation in perimetry -- program Perisim 2000.
AB  - The program Perisim 2000 enables one to simulate the interaction of a number of
      visual field examination strategies with a number of stored visual fields, both
      normal and pathological, with several patterns of observer (patient) behavior. A
      considerable number of visual fields, patient behavior patterns and examination
      strategies, including a full bracketing strategy, Gonzalez de la Rosa's tendency
      oriented perimetry (TOP) and Weber's dynamic program, are available. Statistical
      programs are also incorporated. While the examination strategies to be used in
      the simulations must be selected from a predefined list, new visual field and
      observer patterns may be defined by the user. The results may be shown as
      numerical tables, symbolic or gray tone, pseudocolor or profile displays.
      Cumulative defect curves may also be selected. The learning/teaching benefits of
      the program Perisim 2000 are considerable. It is easy to understand and to
      operate, and ample explanations are available at each step of the program.

PMID- 15947497
TI  - Ptosis secondary to anterior segment surgery and its repair in a two-year follow
      up study.
AB  - OBJECTIVE: Aponeurotic blepharoptosis is a postoperative complication of anterior
      segment surgery with a reported incidence of 1-2% and a variable aetiology. In
      this 2-year follow-up study, we investigated the incidence of this postoperative
      complication in our experience of anterior segment surgery and propose a modified
      technique of aponeurosis advancement for its repair. METHODS: 200 consecutive
      patients undergoing anterior segment surgery in our eye clinic were enrolled in
      the study. Patients who developed any other operative or postoperative
      complication were excluded from the study. In all patients, the following upper
      lid parameters were calculated to determine whether postoperative blepharoptosis
      had occurred: margin-reflex distance, upper eyelid crease, use of frontalis
      muscle and levator function. A questionnaire was submitted to all blepharoptosis
      patients investigating mainly their subjective judgement of the impact of
      blepharoptosis on their quality of life and if they had been informed accurately
      about the incidence of this postoperative complication. RESULTS: 163 patients
      were included in our study. 11 had postoperative blepharoptosis (6.7%). 9
      patients wanted ptosis repair and were operated on with our modified technique.
      None of the 11 ptosis patients had been informed about the possible occurrence of
      the blepharoptosis as postoperative complication. Our modified technique shows
      good, long-lasting results. CONCLUSIONS: Postoperative blepharoptosis is a well
      known postoperative complication of anterior segment surgery. It can be
      successfully treated surgically by aponeurosis advancement. It is our opinion
      that all patients should be informed of the possibility of postoperative
      blepharoptosis when consenting for anterior segment surgery.

PMID- 15947498
TI  - Three-dimensional rotational dacryocystography for imaging of the lacrimal
      draining system and adjacent anatomical structures.
AB  - PURPOSE: A three-dimensional (3D) rotational angiography system was used to
      perform 3D dacryocystography (3DRD) as an adjunct to the conventional
      dacryocystography assisted by digital subtraction angiography (DSA). METHODS: In
      15 patients with severe epiphora, 3DRD was performed after inconclusive results
      from DSA-assisted dacryocystography. RESULTS: 3DRD was technically feasible and
      well tolerated in all 15 cases. In 5 out of 15 patients, 3DRD, in contrast to DSA
      assisted dacryocystography, distinguished clearly between stenotic lesions of the
      canaliculi, lacrimal sac or nasolacrimal duct. In 10 cases, the simultaneous
      display of tear ducts and adjacent structures of the nasal cavity provided
      critical anatomical information for decision making between endoscopic and open
      dacryocystorhinostomy. CONCLUSIONS: 3DRD is technically feasible and adds
      important information to conventional DSA-assisted dacryocystography.

PMID- 15947499
TI  - Electrolytes and electrophoretic studies of tear proteins in tears of patients
      with nasolacrimal duct obstruction.
AB  - This study was performed to determine whether there are differences in tear
      constituents between normal persons and patients with primary acquired
      nasolacrimal duct obstruction (PANDO) and to correlate differences in tear
      composition with the degree of PANDO. We tested 30 normal persons (mean age 42.0
      +/- 21.4 years) and 34 PANDO patients (mean age 44.8 +/- 17.9 years) consisting
      of 18 cases with complete obstruction and 16 cases with partial obstruction. We
      measured the pH, the concentration of Na(+), K(+), Cl(-), total calcium and total
      protein of the tears. The composition of tear protein was assessed by cellulose
      acetate electrophoresis. The data were analyzed by a t test. The pH was more
      alkaline in patients with PANDO (7.11 +/- 0.38), especially in cases with
      complete obstruction (7.14 +/- 0.30, p = 0.47) compared with the normal persons
      (6.94 +/- 0.35). The concentration of Na(+), K(+), Cl(-) and total protein were
      similar in normal and PANDO cases, while total calcium concentration was
      significantly higher in PANDO (2.62 +/- 1.70 mg/dl) compared with the normal
      cases (1.73 +/- 0.97 mg/dl), (p = 0.015). This change was found in both cases
      with complete obstruction (2.47 +/- 1.25 mg/dl, p = 0.027) and cases with partial
      obstruction (3.00 +/- 2.16 mg/dl, p = 0.009). PANDO patients had lower levels of
      tear protein fraction (TPF) 1 (p = 0.006) and higher levels of tear TPF 4 (p =
      0.000) than normal persons. Tears in PANDO cases were more alkaline, higher in
      calcium concentration, and unstable in the proportion of tear proteins compared
      with normal persons. These results may improve our understanding of tear
      physiology and the pathogenesis of PANDO.

PMID- 15947500
TI  - Long-term vitreous replacement with perfluorohexyloctane and silicone oil:
      preliminary reports of a multicentric study.
AB  - AIM: To report on the use of a combined intra-ocular tamponade with silicone oil
      and perfluorohexyloctane (F(6)H(8)) in the treatment of complex retinal
      detachment. DESIGN: A prospective consecutive interventional case series from
      seven study centres. PARTICIPANTS: 69 patients presenting a retinal detachment
      with proliferative vitreoretinopathy (PVR) and retinal breaks of the inferior two
      quadrants of the fundus. METHOD: Patients were divided into two groups: (1) 28
      eyes which had not been operated on before; (2) 41 eyes affected by recurrent
      retinal detachment that had had unsuccessful previous surgery with silicone oil
      or gas tamponade. A pars plana vitrectomy, membrane peeling and -- when necessary
      -- a retinotomy were performed; the vitreous cavity was filled with two thirds of
      F(6)H(8) and one third of silicone oil 1,000 mPas (double filling, DF). The
      endotamponade was removed after 30-45 days (median 38) and replaced by balanced
      salt solution or silicone oil according to the condition of the retina. RESULTS:
      Retinal reattachment was achieved in 52 out of 69 cases (75%) 6 months after
      removal of the DF without any endotamponade. CONCLUSION: The DF with F(6)H(8) and
      silicone oil allows a good endotamponading to the inferior retina and the
      posterior pole. The DF appeared to be well tolerated. Further studies are
      necessary to evaluate whether a DF is advantageous in respect to silicone oil
      filling alone in case of retinal breaks and PVR of the inferior retina.

PMID- 15947501
TI  - Improvement of visual functions and fundus alterations in early age-related
      macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty
      acids, and coenzyme Q10.
AB  - The aim of this randomized, double-blind, placebo-controlled clinical trial was
      to determine the efficacy of a combination of acetyl-L-carnitine, n-3 fatty
      acids, and coenzyme Q10 (Phototrop) on the visual functions and fundus
      alterations in early age-related macular degeneration (AMD). One hundred and six
      patients with a clinical diagnosis of early AMD were randomized to the treated or
      control groups. The primary efficacy variable was the change in the visual field
      mean defect (VFMD) from baseline to 12 months of treatment, with secondary
      efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal
      sensitivity as measured by perimetry, and fundus alterations as evaluated
      according to the criteria of the International Classification and Grading System
      for AMD. The mean change in all four parameters of visual functions showed
      significant improvement in the treated group by the end of the study period. In
      addition, in the treated group only 1 out of 48 cases (2%) while in the placebo
      group 9 out of 53 (17%) showed clinically significant (>2.0 dB) worsening in VFMD
      (p = 0.006, odds ratio: 10.93). Decrease in drusen-covered area of treated eyes
      was also statistically significant as compared to placebo when either the most
      affected eyes (p = 0.045) or the less affected eyes (p = 0.017) were considered.
      These findings strongly suggested that an appropriate combination of compounds
      which affect mitochondrial lipid metabolism, may improve and subsequently
      stabilize visual functions, and it may also improve fundus alterations in
      patients affected by early AMD.

PMID- 15947502
TI  - Lidocaine gel versus combined topical anesthesia using bupivacaine, oxybuprocaine
      and diclofenac eyedrops in cataract surgery.
AB  - PURPOSE: To assess the safety and efficacy of two topical anesthesia regimes for
      cataract surgery. METHODS: 21 patients received a combination of 4 times
      bupivacaine 0.5, oxybuprocaine and diclofenac eyedrops, 18 patients were given a
      single topical application of lidocaine gel 2%. A single intracameral injection
      of lidocaine 1% was administered to all subjects. RESULTS: The extent to which
      the surgeon was bothered by patient motility was graded as low in about two
      thirds of all procedures. Patients reported lower intraoperative pain levels with
      a single application of lidocaine gel supplemented with intracameral lidocaine
      than with a fourfold application of the combination topical anesthesia plus
      intracameral anesthesia. CONCLUSIONS: A single application of lidocaine gel 2%
      combined with intracameral anesthesia provides at least as good analgesia than
      multiple administration of combined topical anesthesia supplemented with
      intracameral anesthesia and is equally safe.

PMID- 15947503
TI  - Comparison of the proliferation and differentiation ability between adult rat
      retinal stem cells and cerebral cortex-derived neural stem cells.
AB  - Recent studies have demonstrated that retinal stem cells (RSCs) and stem cells of
      the central nervous system both exhibited the abilities of self-renewal,
      proliferation and differentiation into multilineage. In the present study, we
      compared the proliferation and differentiation abilities between RSCs and
      cerebral corticex-derived neural stem cells (CNSCs) of adult rats. Stem cells
      isolated from pigmented ciliary margins of eyes and cerebral cortical tissues of
      adult rats were cultured in 96-well plates that contained serum-free medium with
      epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). In
      contrast to RSCs, which stopped proliferating after the 8th week, the total cell
      count of neurospheres in CNSCs increased twofold at the 5th week and more than
      fourfold at the 10th week after in vitro culture. In contrast, RSCs stopped
      proliferating after 8 weeks of culture. After adding 2% fetal calf serum and
      withdrawing EGF and bFGF from the culture medium, the percentages of nestin
      positive cells(20.6 +/- 2.7%), microtubule-associated-protein-2-positive neurons
      (33.2 +/- 3.9%) and glial-fibrillary-acidic-protein-positive glial cells(51.3 +/-
      6.2%) in the differentiated CNSCs were significantly higher than those in the
      differentiated RSCs (10.2 +/- 1.9, 22.3 +/- 1.3 and 44.6 +/- 5.1%, respectively;
      p < 0.05). We also found that the combination of transforming growth factor beta
      type III with retinoic acid played an important role in the induction of CNSCs to
      differentiate into opsin-positive cells. Our data demonstrated that CNSCs
      displayed a higher ability of proliferation and retinal lineage. This report also
      offers an alternative protocol of cell reproduction for producing retinal cells.

PMID- 15947504
TI  - Orbital spread of conjunctival squamous cell carcinoma following evisceration: a
      reminder of the importance of thorough evaluation before and after destructive
      surgery.
AB  - Evisceration is a neglected surgery usually performed by the most junior
      ophthalmologists in unsalvageable eyes with panophthalmitis. It is universal
      knowledge that evisceration is contraindicated in eyes with intraocular
      malignancy. We report 2 patients who presented to us with squamous cell carcinoma
      (SCC) in eviscerated sockets. While one of them was diagnosed with SCC on
      histopathological examination of the eviscerated contents, the other had history
      suggestive of conjunctival SCC prior to evisceration. The second patient
      presented to us with complaints of poorly fitting prostheses. We conclude that it
      is imperative to rule out not just intraocular but also adnexal malignancy prior
      to evisceration, and these eyes should be regularly followed up and carefully
      examined if poor fitting of the prostheses develops.

PMID- 15947505
TI  - Unilateral exophthalmos associated with severe fibrous dysplasia.
AB  - Fibrous dysplasia is a benign developmental anomaly of bone, often affecting
      craniofacial bones. We report on a 9-year-old boy, who presented for routine
      checkup. Clinical examination revealed unilateral exophthalmos of his left eye
      without decrease of visual acuity or double vision. Radiologic studies showed
      characteristic extensive changes of fibrous dysplasia involving the left frontal
      bone, left orbital bones, maxillary and sphenoid bones. The patient was started
      on conservative therapy and the condition of the affected eye remained stable. As
      fibrous dysplasia of the orbital bones can be a cause of significant dysfunction
      and a treatable cause of blindness, early diagnosis is very important. These
      patients are most likely to present with complaints of facial asymmetry,
      including axial, vertical, or horizontal displacement of the globe, or visual
      loss. Therefore the ophthalmologist plays an important role in the early
      diagnosis of fibrous dysplasia.

PMID- 15947506
TI  - Perioperative posterior ischemic optic neuropathy as a rare complication of
      blepharoplasty.
AB  - PURPOSE: To report a case of visual loss to light perception in the right eye
      after upper and lower eyelid blepharoplasty. DESIGN: Case report. METHOD: A 46
      year-old man was referred 3 days after combined bilateral upper and lower lid
      blepharoplasty with visual acuity of light perception in the right eye. The
      fundus examination, fluorescein angiography and magnetic resonance imaging of the
      orbit were normal. Ocular motility was full in all directions of gaze. RESULT:
      The diagnosis of optic nerve damage was initially based on the relative afferent
      pupillary defect. The diagnosis of a perioperative posterior ischemic optic
      neuropathy was based on the Goldmann visual field examination and the subsequent
      optic atrophy. Central visual acuity, color vision as well as the visual field
      improved markedly within 3 months. CONCLUSION: Blindness is a rare but feared
      complication of blepharoplasty and is reported to occur in about 0.04% of cases.
      Although intraorbital hemorrhage is thought to be the leading cause for optic
      nerve damage in most of the patients with this devastating condition, we present
      a case with perioperative posterior ischemic optic neuropathy leading to visual
      loss after blepharoplasty. The mechanism leading to optic nerve damage in this
      patient may include compromised small arteries perfusing the optic disk due to
      direct mechanical compression and a probable vasoconstrictive activity of the
      anesthetic agent.

PMID- 15947507
TI  - Improvement of visual acuity in eyes with diabetic macular edema after treatment
      with pars plana vitrectomy.

PMID- 15947508
TI  - Why new psychotherapies for posttraumatic stress disorder?

PMID- 15947509
TI  - Autodestructive syndromes.
AB  - BACKGROUND: The phenomenon 'autodestructive behaviour' is becoming an
      increasingly serious disease and cost factor in a wide range of medical fields.
      The present paper presents a survey of the literature on autodestructive
      behaviour, excluding psychotic, substance-induced or organic brain disorders.
      Starting out with a conceptual overview, the paper goes on to look into the
      epidemiology of autodestructive behaviour and the forms in which it manifests
      itself. METHOD: A literature search was conducted in Medline, Psycinfo and
      Psyndex using the search terms 'artifact', 'artificially induced',
      'autodestructive', 'self-mutilation', 'factitious', 'self-harm', 'self-induced',
      'self-inflicted', 'self-injuring' and 'self-mutilation' for the period from 1977
      to 2003. RESULTS: Five of a total of 18 empirical studies describe the
      simultaneous occurrence of direct and indirect forms of autodestructive
      behaviour. Reported prevalence rates range from 0.032% to 9.36%. The ratio of
      females to males was found to be 2:1 (average age: 31.5 years; SD: 9.3 years); in
      contrast, the gender ratio was reversed for Munchausen's syndrome. The case
      history data presented are patchy and differ in terms of their priorities. We
      found a large number of codiagnoses, which seems to indicate that personality and
      dependence disorders, or substance misuse, are characteristic of both direct and
      indirect forms of autodestructive behaviour. CONCLUSIONS: The task at hand is to
      use a yet-to-be-developed nomenclature and adequately operational diagnostic
      criteria to work out standardised survey instruments that do justice to the
      heterogeneity of this disorder complex.

PMID- 15947510
TI  - Alternatives to debriefing and modifications to cognitive behavior therapy for
      posttraumatic stress disorder.
AB  - BACKGROUND: Psychological debriefing uses brief unsystematic exposure, and is
      ineffective for posttraumatic stress symptoms and disorder. Systematic exposure
      alone and cognitive restructuring alone are each effective. Other approaches too
      may be useful. METHODS: The treatment of 3 posttraumatic stress disorder (PTSD)
      patients is detailed in which there was no exposure to the main traumatic event.
      There was exposure to related cues in case 1, exposure to related and other cues
      followed by well-being therapy (WBT) in case 2 and WBT in case 3. RESULTS: The 3
      patients improved enduringly, confirming earlier findings that exposure to the
      main trauma is not essential for PTSD to improve. CONCLUSIONS: A study is needed
      of therapeutic mechanisms in PTSD and of the value of WBT in a randomized
      controlled trial.

PMID- 15947511
TI  - Cognitive behaviour group therapy for chronic fatigue syndrome: a non-randomised
      waiting list controlled study.
AB  - BACKGROUND: It has been demonstrated that individual cognitive behaviour therapy
      is an effective treatment for chronic fatigue syndrome (CFS). The aim of the
      present study was to investigate the effectiveness of cognitive behaviour group
      therapy (CBGT) in an unselected group of CFS patients. Additionally, pretreatment
      characteristics of CFS patients who improve after CBGT were explored. METHODS: In
      a non-randomised waiting list controlled design, 31 patients were allocated to
      CBGT and 36 to the waiting list condition. CBGT consisted of 12 two-hour sessions
      during 6 months. Main outcome measures were fatigue (Checklist Individual
      Strength) and functional impairment (Sickness Impact Profile). RESULTS: A
      moderate effect on fatigue in favour of CBGT was found. For functional
      impairment, the effect was opposite to what was expected. Patients who improved
      after CBGT had less complaints at baseline compared to patients who did not
      improve. CONCLUSIONS: An explanation for the moderate effect might be that during
      CBGT, rest and relaxation were too much emphasised. Furthermore, an unselected
      group of CFS patients and therapists inexperienced in CB(G)T for CFS
      participated. Suggestions to improve CBGT for future research are given.

PMID- 15947512
TI  - Increased recognition of depression in primary care. Comparison between primary
      care physician and ICD-10 diagnosis of depression.
AB  - BACKGROUND: Underrecognition and undertreatment of depression in primary care has
      been regarded as a major public health problem. In contrast, some studies found
      that among patients labeled as depressed by primary-care physicians (PCPs), a
      relevant proportion do not satisfy international diagnostic criteria for
      depression. The aims of this study are: (1) to assess disparity between PCP
      diagnosis and research diagnosis of depression; (2) to compare antidepressant
      treatment in concordant and discordant cases of depression. METHODS: Data are
      gathered from a national survey on depressive disorders in primary care,
      conducted with the collaboration of 191 PCPs. Three hundred and sixty-one PCP
      patients were evaluated, and their psychiatric diagnosis was established by the
      'unaided' PCPs and by using a research interview for depression. RESULTS: PCPs
      recognized 79.4% of cases of depression and prescribed antidepressants to 40.9%
      of them. Yet, 45.0% of patients labeled as depressed by the PCPs were not cases
      of depression according to ICD-10 criteria; 26.9% of false-positive cases
      received an antidepressant. Globally, 35% of antidepressants for 'depression'
      were prescribed to false-positive cases. CONCLUSIONS: Underrecognition and
      undertreatment of depression in primary care seem to be less alarming.
      Conversely, PCP diagnoses of depression appear to be more inclusive than
      psychiatric diagnostic criteria. A possible consequence of this apparently more
      inclusive diagnostic threshold may be an excessive use of antidepressants. These
      changes require a corresponding change in research, toward efficacy and safety of
      the treatment of milder cases, and in education, toward the distinction between
      the management of mild and severe cases of depression.

PMID- 15947513
TI  - In the face of pain: the relationship between psychological well-being and
      disability in women with fibromyalgia.
AB  - BACKGROUND: Few studies have examined the potentially beneficial role of positive
      psychological functioning in individuals with chronic pain. This study examined
      the relationship of psychological well-being (PWB) to pain and disability in
      women with fibromyalgia (FM) as compared to women with rheumatoid arthritis (RA)
      and healthy controls (HC). We targeted several domains of PWB that have been
      associated with health, and also tested whether PWB was related to the women's
      social network. METHODS: PWB, pain, and disability were assessed in 125 women (57
      with FM, 20 with RA, and 48 HC) on two occasions. RESULTS: Women with FM reported
      lower overall PWB than did RA and HC women. Further, greater PWB was associated
      with less disability and fatigue, but not pain in women with FM. Self-acceptance,
      environmental mastery, purpose in life, and positive relations with others
      emerged as four important constructs in the association between PWB and
      disability. In addition, PWB mediated the relationship between social network
      size and disability. CONCLUSIONS: This assessment of PWB provides insight into
      those psychological domains that should be emphasized in treatments aimed at
      reducing the disabling aspects of FM.

PMID- 15947514
TI  - Alexithymia and interpersonal problems.
AB  - BACKGROUND: Interpersonal relationships are substantially codetermined by
      nonverbal communication, e.g. facial affect. Given the deficits of nonverbal
      affect recognition and expression in alexithymia, we hypothesized that
      alexithymics had more interpersonal problems than nonalexithymic individuals, and
      that the various facets of the alexithymia construct are differentially related
      to interpersonal problems. METHOD: 149 subjects participating in an inpatient
      group psychotherapy program completed the Toronto Alexithymia Scale (TAS-20) and
      the Inventory of Interpersonal Problems (IIP-C) at the beginning of the
      treatment. The IIP-C was also administered to a subgroup at the end of the
      treatment. RESULTS: Based on the alexithymia scores, patients were classified as
      low- (TAS-20 score </=51), moderate- or high-alexithymic (TAS-20 score >/=61).
      High-alexithymic patients had significantly more interpersonal problems than low
      alexithymics, particularly in the IIP-C scales indicating hostility and social
      avoidance. The TAS-20 subscale difficulty describing feelings showed the highest
      correlations with interpersonal problems (r between 0.23 and 0.55). At the end of
      the treatment, the high alexithymics still scored highest on the IIP-C, but the
      magnitude of change in interpersonal problems did not differ across the groups.
      CONCLUSIONS: Our findings suggest that the interpersonal style of alexithymic
      individuals is characterized by a cold and socially avoidant behavior,
      corresponding to the predominantly insecure attachment pattern found in
      alexithymia. Additionally, our results indicate that group psychotherapy is as
      helpful for alexithymic as for nonalexithymic subjects with respect to
      interpersonal problems. Finally, we propose that alexithymia involves a reduced
      capacity to use social interactions for affect regulation.

PMID- 15947515
TI  - Childhood body-focused behaviors and social behaviors as risk factors of eating
      disorders.
AB  - BACKGROUND: The risk factors for adolescent eating disorders are poorly
      understood. It is generally agreed, however, that interactions with one's body
      and interactions with others are two important features in the development of
      anorexia and bulimia nervosa. Therefore, we assessed a variety of childhood body
      focused behaviors and childhood social behaviors in eating-disordered patients as
      compared to non-eating-disordered subjects. METHOD: We compared 50 female
      inpatients with eating disorders (anorexia or bulimia nervosa), 50 female
      inpatients with polysubstance dependence, and 50 nonpatient female control
      subjects with no history of eating or substance abuse disorders (all defined by
      DSM-IV criteria), using a semi-structured interview of our own design. We asked
      questions about (1) childhood body-focused behaviors (e.g. thumb-sucking) and
      body-focused family experiences (e.g. bodily caresses), and (2) childhood social
      behaviors (e.g. numbers of close friends) and family social styles (e.g.
      authoritarian upbringing). RESULTS: Many body-focused measures, such as feeding
      problems, auto-aggressive behavior, lack of maternal caresses, and family taboos
      regarding nudity and sexuality, characterized eating-disordered patients as
      opposed to both comparison groups, as did several social behaviors, such as
      adjustment problems at school and lack of close friends. However, nail-biting,
      insecure parental bonding, and childhood physical and sexual abuse were equally
      elevated in both psychiatric groups. CONCLUSION: It appears that eating
      disordered patients, as compared to substance-dependent patients and healthy
      controls, show a distinct pattern of body-focused and social behaviors during
      childhood, characterized by self-harm, a rigid and 'body-denying' family climate,
      and lack of intimacy.

PMID- 15947516
TI  - An evaluation of the 'Coping with Depression Course' for relapse prevention with
      unipolar depressed patients.
AB  - BACKGROUND: Patients with treated episodes of depression are at high risk of
      relapse and recurrence. This study describes the clinical course of patients who
      had received cognitive-behavioral group intervention for relapse prevention.
      METHOD: Forty-four remitted unipolar depressed patients with recently treated
      episodes of illness participated in a 16-week group program, the 'Coping with
      Depression Course' (CWD). The majority of patients had suffered from multiple
      episodes of depression and nearly half of them were only partially remitted when
      they started the program. Assessments took place throughout the intervention and
      17-23 months after the pretest. Descriptive analyses included proportions of
      reliable and clinically significant improvements, and cumulative relapse rates
      were estimated using survival analysis. RESULTS: At posttest, residual depression
      and dysfunctional attitudes had significantly decreased. Improvements were
      similar in patients with and those without parallel antidepressant medication.
      Two thirds of patients starting within a dysfunctional depression range showed a
      clinically significant improvement at the end of the intervention. The estimated
      cumulative relapse rates at 6, 12, 17, and 23 months after pretest were 13.6,
      30.0, 37.0 and 44.9%. CONCLUSIONS: Participants appeared to be protected from
      relapse during active intervention, but a substantial proportion suffered
      relapses in the postintervention period. Further research into the CWD is needed
      within the framework of randomized controlled trials.

PMID- 15947517
TI  - National Comorbidity Survey data concerning cancer and depression lack
      credibility.

PMID- 15947519
TI  - [Evaluation of the human and animal embryos' quality (Review of methods)].
AB  - The aim of this article was to review different methods that are used for the
      evaluation of human and animal embryos' quality. Techniques for the production in
      vitro of various mammalian species embryos have been developed worldwide. Using
      modern methods for maturation of oocytes, fertilization and embryos' culture in
      vitro about 30-40% of bovine and 10-20% of human oocytes develop to blastocyst
      stage and can be used for transfer. Evaluation of embryos' quality is problematic
      not only for every researcher involved in embryology but also for every clinician
      who wants to select the best embryos for transfer. Lithuanian researchers and
      clinicians could also apply these worldwide popular methods for the evaluation of
      embryos' quality.

PMID- 15947520
TI  - [An eleven-year experience of eye enucleation caused by severe ocular injuries].
AB  - The objective of this study was to evaluate indications for primary and delayed
      enucleation caused by severe eye injuries. MATERIAL AND METHODS: One hundred nine
      enucleations performed in the Clinic of Eye Diseases of Kaunas University of
      Medicine Hospital during 1993-2003 years because of severe ocular injuries were
      analyzed retrospectively. Fifty seven of the eyes were enucleated primarily and
      52 enucleations were delayed for later period. RESULTS: The most common
      indications for primary enucleation were: loss of internal eyeball tissues in 40
      (74.1%) cases; wide tissue defect--5 (9.3%) cases; long wound--4 (7.4%) cases;
      endophthalmitis and panophthalmitis--5 (9.3%) cases. The most frequent
      indications for delayed enucleation were: endophthalmitis and panophthalmitis in
      28 (59.6%) cases; atrophia and phthisis bulbi--13 (7.7%) cases; secondary
      glaucoma--6 (12.8%) cases. CONCLUSIONS: Amount of enucleations performed in the
      Clinic of Eye Diseases of Kaunas University of Medicine Hospital because of
      severe ocular injuries was without a significant change during ten-year period.
      Enucleations were performed more frequently in male patients of employable age.
      The most common causes for enucleation were open globe injury and penetrating
      wound. Loss of internal eyeball tissues, wide tissue defect, long wound,
      endophthalmitis and panophthalmitis were the most common indications for primary
      enucleation. The most frequent indications for delayed enucleation were:
      endophthalmitis and panophthalmitis, atrophia and phthisis bulbi, secondary
      glaucoma.

PMID- 15947521
TI  - Impact of different treatment methods on survival in advanced pancreatic cancer.
AB  - The aim of the study was to evaluate the impact of different treatment methods on
      survival of patients treated for advanced pancreatic cancer at Kaunas University
      of Medicine Hospital from 1987 to 2003. MATERIALS AND METHODS: Data on 262
      patients with advanced pancreatic cancer treated from 1987 to 2003 were analyzed
      retrospectively. Four groups of patients were analyzed. One hundred eighty
      patients underwent palliative bypass or endoscopic bile duct stenting or
      observation alone. Forty three patients in addition to surgery were treated by
      radiotherapy. Twenty five patients received gemcitabine in standard doses and
      schedules. Fourteen patients received concomitant chemoradiotherapy (with
      gemcitabine or 5-fluorouracil). All patients were grouped by treatment method and
      median survival was analyzed. RESULTS: Median survival of patients treated by
      palliative surgery only or observation alone was 1.9 month, and for patients
      treated by palliative surgery and radiotherapy was 6.1 months (p=0.00007). Median
      survival of patients treated with gemcitabine was 9.5 months (p<0.001), and
      median survival of patients treated with concomitant chemoradiotherapy was 8.5
      months (p=0.00003). CONCLUSION: Patients diagnosed with advanced pancreatic
      cancer in addition to surgical treatment should be treated by chemotherapy,
      concomitant chemoradiotherapy or radiotherapy.

PMID- 15947522
TI  - Etiology of bile infection and its association with postoperative complications
      following pancreatoduodenectomy.
AB  - Currently controversy exists whether bile infection following preoperative
      biliary drainage has an impact on postoperative complications and mortality rate.
      The objective of the study was to determine etiology of preoperative bile
      infection and to evaluate its influence on postoperative complications and
      mortality after pancreatoduodenectomy. METHODS: Data on 64 patients, undergoing
      pancreatoduodenectomy at Kaunas University of Medicine Hospital between 2002 and
      2004 were collected prospectively. We evaluated etiology and the impact of bile
      infection on development of post-operative complications. Patients were divided
      into groups according to results of intraoperative bile culture. RESULTS: In 31
      patients (48.4%) intraoperative bile cultures were negative, while in remaining
      33 patients (51.6%) infected bile was documented. Both patient groups were
      homogenous according to demographic data, preoperative and intraoperative
      variables. Pancreaticoduodenectomy was performed in 21 patients after
      preoperative biliary drainage (endoscopic stenting, bilidigestive anastomosis or
      percutaneous bile drainage), others (n=43) had primary operation. Infected bile
      was found more often in patients who underwent biliary drainage (p<0.0001). Among
      43 patients with primary pancreaticoduodenectomy 22 patients underwent endoscopic
      retrograde cholangiopancreatography without stenting, while remaining 21 had no
      preoperative endoscopic manipulation. Infected bile was present in 9 patients
      after endoscopic retrograde cholangiopancreatography (40.9%) and in 4 without
      preoperative endoscopy (19%). Enterococcus and Escherichia coli dominated in bile
      cultures of patients with primary pancreaticoduodenectomy, while multiple species
      (3 and more microorganisms) dominated following drainage procedures. Septic
      postoperative complications were identified in 26.6% of cases. Infected bile did
      not influence both overall and septic postoperative complications. Bacteria
      causing abdominal cavity and wound infections matched bile cultures in 7.7% of
      cases only. CONCLUSIONS: Our data show that infected bile is found more often
      after preoperative biliary drainage procedures. However, bile infection did not
      increase statistically significantly the number of postoperative septic
      complication.

PMID- 15947523
TI  - The effects of the Twin-block appliance treatment on the skeletal and
      dentolaveolar changes in Class II Division 1 malocclusion.
AB  - Class II Division 1 malocclusion is the most frequent problem in the orthodontic
      practice. During the last ten years treatment with Twin-block functional
      appliance has gained popularity. The aim of the present study was to analyze the
      skeletal and dentoalveolar changes in Class II Division 1 malocclusions cases
      treated with Twin-block appliance. MATERIAL AND METHODS: Cephalometric analysis
      of skeletal and dentoalveolar facial structures of 34 Class II Division 1
      patients treated with Twin-block appliance was performed using the same reference
      system before and after treatment. Longitudinal growth records of persons with
      excellent occlusion-Bolton standards have been used for the control in order to
      assess natural growth. RESULTS: Mandibular length as measured from point
      Articulare to point Pogonion increased by 4.6 mm in the Twin-block group compare
      with 2.2 mm in the control Bolton standards group. Skeletal and dentoalveolar
      relationship between maxillary and mandibular bases improved significantly: ANB
      angle reduced by 2.3 degrees, overjet reduction was 4.7 mm, postnormal molar
      position corrected by 3.6 mm. CONCLUSIONS: Twin-block appliance statistically
      significantly increases mandibular length by 2.4 mm during 12-month treatment
      period. With the Twin-block treatment about 40% overjet correction was achieved
      by skeletal and about 60% by dentoalveolar changes. Correction of postnormal
      buccal segments in Twin-block group was achieved by the combination of distal
      movement of the upper molars (0.7 mm dentoalveolar, 0.3 mm skeletal) and forward
      migration of lower molars (0.9 mm dentoalveolar and 1.7 mm skeletal).

PMID- 15947524
TI  - Effect of hyperosmolarity on beta2-adrenergic stimulation in human atrium.
AB  - The purpose of the present study was to determine whether extracellular osmotic
      pressure modulates beta2-adrenergic stimulation of the contraction force and L
      type Ca2+ current in human atrial myocytes. Experiments were performed on human
      atrial trabeculae and myocytes isolated from the right atrium. We have studied
      the effect of salbutamol (SAL), a beta2-adrenoceptor agonist, on peak tension
      (P), time to half peak tension (tc), time to half relaxation (tr), resting
      tension (contracture) (C) and L-type calcium current (ICaL) under isosmotic (345
      mOsm) and hyperosmotic (525 mOsm in experiments for P, and 405 mOsm for ICaL)
      conditions. Salbutamol (10(-8)/10(-5) M) added to the control solution increased
      P, with a half-stimulation constant EC50=(2.7+/-0.6)x10(-8) M (p<0.05) and the
      maximal stimulation of contraction force Pmax=180.6+/-45.8% (n=10). The time to
      half peak and time to half relaxation were reduced by salbutamol to 89.1+/-2.7%
      and 78.8+/-4.1% (n=8), respectively. Mannitol (180 mM) added to the Tyrode
      solution decreased Pmax to 34+/-5.5%; tc, tr and C were increased to 126.3+/
      7.2%, 158.3+/-22.6% (n=4) and 0.54+/-0.22 (n=5) of the control level,
      respectively. Under these hyperosmotic conditions the same concentrations of SAL
      increased P with a half-stimulation constant EC50=(6.4+/-2.6)x10(-7) M and
      Pmax=57.2+/-12.6% (n=4). The tc and tr were reduced by 23.2+/-5.9% and 53.1+/
      19.4% (n=4), respectively (as compared to mannitol). There was no significant
      effect of salbutamol on the resting tension induced by mannitol. Under isosmotic
      conditions salbutamol (10(-9)/10(-6) M) increased ICaL with an EC50 value of
      (2.9+/-0.9)x10(-9) M and Emax 182.3+/-19.8% (n=4). In hyperosmotic solutions the
      EC50 and Emax for ICaL were (1.2+/-0.5)x10(-8) M and 217.2+/-70.5%, respectively
      (n=5). These results indicated that hyperosmolarity reduced the effect of beta2
      adrenergic stimulation on human atrial cells.

PMID- 15947525
TI  - Alcohol addiction of adolescents and risk factors related to this habit.
AB  - Objective of this study was to assess the prevalence of alcohol use among
      schoolchildren and to determine its factors. The study was conducted in schools
      of Kaunas city and its region among schoolchildren of 7th, 9th and 11th grades-
      overall 410 pupils. Most of schoolchildren (93.4%) acknowledged that they had
      used some alcohol drinks; 37.6% of boys and 27.3% of girls (p<0.05) used alcohol
      especially large number of times (40 and more). Every second pupil, irrespective
      of his sex, stated being intoxicated with alcohol in the last month. Main motives
      that induced to use the alcohol were: wish to relax, curiosity, having nothing to
      do as well as wish to experience the state of intoxication, wish not to differ
      from group friends. The logistic analysis demonstrated a statistically
      significant relation between alcohol use and smoking, and positive point of view
      to drugs and people who use them. The summarized data could serve in planning
      well-founded prevention programmes. CONCLUSION: The alcohol addiction of
      schoolchildren at higher grades is very prevalent and correlates with smoking and
      drugs usage. Therefore, the implementation of effective health promotion
      programmes that include alcohol and drug prevention at school is urgently needed.

PMID- 15947526
TI  - [The influence of smoking on oral health].
AB  - Smoking is a serious risk factor for many diseases. The determining of smoking as
      a harmful habit among young people is very important. We examined 618 (mean age
      21+/-2.9 years) young Lithuanian men. The findings of our research showed that
      70% of young men smoked. The analysis of the research findings showed that
      smoking had a negative effect on oral hygiene. Young men who smoke daily had
      significantly higher oral hygiene index than those who do not smoke (Simplified
      Oral Hygiene Index (OHI-S)=2.9(1.0) and OHI-S=2.2(1.2), respectively; p<0.001).
      Smoking is especially harmful to the periodontal tissues. The periodontal lesions
      were more prevalent and severe among young men who smoke. It is confirmed by the
      fact that smokers had significantly higher Community Periodontal Index of
      Treatment Needs (CPITN) than nonsmokers (CPITN=1.5(0.7) and CPITN=1.2(0.8),
      respectively; p<0.001). Our findings show that smoking increased the possibility
      of having decayed untreated teeth and this shows young men's careless attitude to
      their oral health. There was no difference in the prevalence of smoking among men
      who live in the countryside and those who live in the city. However, the men with
      poorer education smoked more frequently.

PMID- 15947527
TI  - [Oral hygiene of preschool children in Kaunas city and their parents' attitude
      towards children's oral health].
AB  - The aim of the study was to evaluate oral hygiene of the preschool children,
      their oral hygiene behavior and their parents' attitude towards children's oral
      health. In the present study 1656 preschool children were examined and 958
      parents completed a questionnaire on oral hygiene, parental attitudes to
      children's oral health. The findings of the study showed that oral hygiene status
      was not satisfactory even in 43.2% of children (values of Simplified Oral Hygiene
      Index varied from 1.1 to 6.0). No statistically significant difference was found
      between boys and girls. According to the parents' answers to the questions about
      oral hygiene habits it was found that 41.0% of parents brush their teeth
      irregularly. Fourteen percent of parents brushed their children teeth, only 5.0%
      of parents started to brush children's teeth when the first tooth erupted, 21.2%
      took their child to a dentist systematically and 31.7% of children visited the
      dentist for the first time due dental pain. Nearly a half of parents (44.9%)
      referred that their children's teeth started to decay at the first year of their
      lives. However, even 12.0% of parents refused to include their children in
      preventive program on dental caries.

PMID- 15947529
TI  - [Professor Juozas Blazys--psychiatrist, academic and public figure].
AB  - Juozas Blazys (1890-1939)--the first chief of the Department of Nerve and
      Psychiatric Illnesses and Vice Rector of Lithuanian Vytautas Magnus University in
      the interwar period. In 2004 we commemorated the 65th anniversary of his death.
      He was a highly prominent personality of enormous erudition and productive
      scientist. He wrote a coursebook "Introduction to psychiatry", monograph-study
      "Tolerance, as a basis of culture", published around 100 articles in "Medicina"
      and various journals of that period. His ideas about psychiatry are relevant
      nowadays too. Professor was interested in the causes of psychosis origin,
      analyzed alcoholic, somatogenic psychosis, was interested and working in the
      fields of forensic psychiatry, military expertise, heredity and is contradictory
      evaluated in the field of eugenics till now. Juozas Blazys was born in Siauliai.
      In 1914 he graduated Petersburg Academy of Military Medicine, worked at the
      various hospitals of Russian military. In 1918 he returned to Lithuania and
      started to work at the psychiatric hospital in Taurage at first as a chief of
      department, and later as director, at the same time working as a physician of
      Taurage district. In 1920-1921 Juozas Blazys lectured the course of psychiatry at
      Higher Courses of Study in Kaunas. In 1924, after the establishment of the
      University of Kaunas, he was elected as a chief of the department of Nerve and
      Psychiatric Illnesses. In 1935 he was granted the degree of professor, in 1938-
      appointed as Vice Rector of Vytautas Magnus University. He had been developing
      educative activities: wrote articles on psycho hygiene, negative impact of
      alcohol, smoking and prostitution on heredity, cared about the improvement of
      Lithuanian genotype.

PMID- 15947528
TI  - [Association of metabolic syndrome with ischemic heart disease among middle-aged
      Kaunas population].
AB  - The aim of the present study was to estimate an association of metabolic syndrome
      with ischemic heart disease (IHD) in middle-aged Kaunas population. MATERIAL AND
      METHODS: The epidemiological examination was carried out in Kaunas from 2001 to
      2002. Health survey was carried out according to the MONICA study protocol.
      Analysis was performed in 1336 persons aged 35-64 years (603 men and 733 women).
      Metabolic syndrome was defined by the presence of three or more out of five
      components: central obesity (waist circumference >102/88 cm (men/women)); fasting
      plasma glucose > or =6.1 mmol/l; triglycerides > or =1.7 mmol/l; high density
      lipoprotein cholesterol <1.04/1.3 mmol/l (men/women); systolic/diastolic blood
      pressure > or =130 and/or 85 mmHg. IHD was diagnosed by the criteria: previous
      myocardial infarction, angina pectoris or ischemic changes of electrocardiogram.
      RESULTS: In the study population cohort prevalence of metabolic syndrome was
      19.4% for men and 26.3% for women, prevalence of IHD--14.3% and 19.4%,
      respectively. Prevalence of metabolic syndrome and IHD among men and women
      increased with age. Comparing prevalence of metabolic syndrome among persons with
      IHD and without IHD, in the groups of men and women aged 35-44 years metabolic
      syndrome was not associated with IHD; in the group of men with IHD aged 45-64
      years rate of metabolic syndrome was 1.8 times higher than among persons without
      IHD (odds ratio: 2.25 (95% CI 1.24-4.06)); in the group of women with IHD aged 45
      64 years the rate of metabolic syndrome was marginally higher (1.3 times) than
      among women without IHD (odds ratio: 1.55 (95% CI 0.99-2.43)). The highest rate
      of metabolic syndrome was determined for men diagnosed with angina pectoris (odds
      ratio: 3.39 (95% CI 1.36-8.41)). In conclusion, study data showed that metabolic
      syndrome was associated with IHD in men aged 45-64 years.

PMID- 15947530
TI  - [Hydroxyethyl starch solutions].
AB  - Hypovolemia is common among surgical, trauma, and intensive care unit patients.
      It can occur in the absence of obvious fluid loss secondary to vasodilatation or
      during generalized alterations of the endothelial barrier resulting in increased
      capillary permeability. Hydroxyethyl starch solutions are increasingly used for
      the volume replacement therapy. Hydroxyethyl starch solutions are synthetic
      colloids with the pharmacological properties that are the closest to natural
      colloids. Important characteristics for these products are molecular weight,
      their concentration, the degree of molar substitution, and the substitution
      pattern. In this review article a large variety of hydroxyethyl starch solutions,
      their physical and chemical characteristics, pharmacokinetics and metabolism, the
      main route of elimination, mechanism of action, effect on blood plasma volume,
      safety, tolerability and side effects (the risk of adverse effects on hemostasis,
      platelet function, frequency of pruritus, anaphylactoid reaction, incidence of
      rise in serum amylase) are presented.

PMID- 15947531
TI  - Effect of Orlistat in obese patients with heart failure: a pilot study.
AB  - Heart failure is the leading cause of hospitalization. Obesity is increasingly
      common and is a major public health problem. The aim of this study is to assess
      whether obese patients with heart failure can benefit from losing weight via an
      orlistat-assisted diet. This randomized clinical trial included obese patients
      with ejection fractions < or =40%. Orlistat and diet counseling were compared
      with diet counseling alone. Twenty-one consecutive obese patients with heart
      failure were recruited. Significant improvement in 6-minute walk test (45.8 m;
      95% confidence interval, 5.2-86.4 m; p=0.031), functional class (-0.6+/-0.5,
      p=0.014), weight loss (-8.55 kg; 95% confidence interval, -13.0 to -4.1 kg;
      p<0.001) and also significant decreases in total cholesterol (p=0.017), low
      density lipoprotein cholesterol (p=0.03), and triglycerides (p=0.036) were
      observed in the orlistat group. Orlistat can promote significant weight loss and
      symptoms of relief in obese patients with heart failure, as measured by 6-minute
      walk test and functional capacity. The lipid profile improved. Orlistat was safe
      and well tolerated.

PMID- 15947532
TI  - Heart failure drug utilization patterns for Medicaid patients before and after a
      heart failure-related hospitalization.
AB  - The authors examined heart failure (HF) drug utilization patterns in Medicaid
      patients before and after a HF-related hospitalization. This was a retrospective
      claims analysis of Kansas Medicaid beneficiaries hospitalized for HF between July
      1, 2000, and March 31, 2001. HF drugs were tracked 6 months prior and 6 months
      following the admission. Angiotensin-converting enzyme (ACE) inhibitor doses were
      compared with target ranges. The cohort of 135 patients had a mean age of 53.6
      years and was predominantly female (66.7%) and Caucasian (70.4%) with a high
      prevalence of cardiovascular comorbidities. Before hospitalization, less than one
      third of patients were receiving ACE inhibitors, angiotensin receptor blockers,
      beta blockers, digoxin, or vasodilators. Following hospitalization, increased
      utilization was observed for beta blockers, digoxin, and angiotensin receptor
      blockers, but overall usage remained low. ACE inhibitors and vasodilator use
      remained constant. ACE-inhibitor doses were below target ranges before and after
      hospitalization. In this Medicaid cohort, HF-related hospitalizations did not
      lead to improved HF therapy.

PMID- 15947533
TI  - Anemia, chronic heart failure, and the impact of male vs. female gender.
AB  - Anemia is common in subjects with chronic heart failure, and correction of anemia
      improves quality of life and exercise capacity in both men and women. The
      definition of anemia is sex-specific, but enrollment criteria of studies
      examining the effects of recombinant human erythropoietin in chronic heart
      failure to date have not taken sex into account. Indeed, it is unknown whether
      sex-specific differences of hemoglobin values observed in normal individuals are
      maintained in subjects with chronic disease and volume overload states. Given the
      significant treatment implications for sex-specific differences in hemoglobin
      values, the authors analyzed data for 260 subjects consecutively admitted with
      decompensated chronic heart failure. In a multivariate regression analysis
      controlling for serum creatinine and age, female sex was independently associated
      with lower hemoglobin. When deciding upon initiation of treatment in this
      population, sex-specific targets should be applied.

PMID- 15947534
TI  - Long-term destination therapy with the HeartMate XVE left ventricular assist
      device: improved outcomes since the REMATCH study.
AB  - The Randomized Evaluation of Mechanical Assistance for the Treatment of
      Congestive Heart Failure (REMATCH) trial demonstrated increased 1- and 2-year
      survival and improved quality of life for end-stage heart failure patients
      implanted with the HeartMate VE Left Ventricular Assist Device (LVAD) (Thoratec
      Corporation, Pleasanton, CA) compared with optimal medical management. This is
      the first report of Destination Therapy (DT) experience since REMATCH and
      incorporates improvements with the HeartMate XVE LVAD and patient management.
      Forty-two patients with end-stage heart failure at higher volume institutions
      were supported with the LVAD over a duration of 26.7 patient years (mean 232
      days). Compared with REMATCH, DT patients had a 40% lower rate of death (0.49 vs.
      0.84 deaths per patient year). Kaplan-Meier estimates of survival in the DT and
      REMATCH LVAD groups at 30 days were 90% and 81%, and at 1 year were 61% and 52%.
      The death rate due to sepsis was 8.3 times lower in DT patients (risk ratio,
      0.12; 95% confidence interval, 0.02-0.90). DT patients were 2.1 times less likely
      to experience an adverse event (risk ratio, 0.47; 95% confidence interval, 0.35
      0.63). These results demonstrate continued improvement with outcomes in long-term
      DT with LVADs. Given that these DT patients were similar to those in the REMATCH
      trial, the improved outcomes likely reflect improvements in the HeartMate XVE
      LVAD and experience with patient management.

PMID- 15947535
TI  - The acute hemodynamic effect of IV nitroglycerin and dipyridamole in patients
      with pulmonary arterial hypertension: comparison with IV epoprostenol.
AB  - Nitroglycerin and dipyridamole are two commonly available and well tolerated
      vasoactive medications. Their acute hemodynamic effects in patients with
      pulmonary arterial hypertension are not well defined in the current literature.
      The authors retrospectively analyzed the acute hemodynamic effects of IV
      nitroglycerin, dipyridamole, and epoprostenol in 59 patients with pulmonary
      arterial hypertension as determined by changes from baseline in systemic and
      pulmonary hemodynamic parameters. Statistical analysis was performed using the
      independent sample t test. A p value <0.05 was considered significant.
      Nitroglycerin is predominantly a vasodilator of the pulmonary vasculature with
      moderate systemic vasodilator effect, while dipyridamole is primarily a positive
      inotropic agent. Epoprostenol is a potent vasodilator of both pulmonary and
      systemic vessels and a strong positive inotropic agent. Nitroglycerin and
      dipyridamole may be useful in the acute management of pulmonary arterial
      hypertension.

PMID- 15947536
TI  - New graduated pressure regimen for external counterpulsation reduces mortality
      and improves outcomes in congestive heart failure: a report from the Cardiomedics
      External Counterpulsation Patient Registry.
AB  - External counterpulsation (ECP) has been shown to increase exercise tolerance and
      reduce angina episodes, Canadian Cardiovascular Society Functional (CCSF) class,
      anginal medication usage, and hospitalizations in refractive CCSF class III and
      IV stable angina. However, the high pressures and resulting 1.5:1-2:1 peak
      diastolic to peak systolic pressure (D/S) ratios shown to be optimal in the
      treatment of angina can cause excessive preload and adverse effects in congestive
      heart failure (CHF) patients, particularly those with left ventricular ejection
      fractions <40%. Data were retrospectively analyzed from the Cardiomedics ECP
      Registry on 127 New York Heart Association (NYHA) class II-IV CHF patients (79.6%
      men; average age +/- SD, 68.2+/-15.6 years), with a comorbidity of CCSF class III
      IV refractive angina, who were serially treated with 35 hours of ECP (1 h/d, 5
      d/wk for 7 weeks) at unconventionally low pressures and D/S ratios under a new
      graduated pressure regimen. The pressures and D/S ratios were gradually increased
      in stages over the 7-week ECP regimen. The patients were divided into three
      groups based on the pressures applied and the resulting average D/S ratios (Low,
      Mid, and High). In the Low D/S ratio group (average D/S ratio 0.7:1), all-cause
      mortality in the year following ECP treatment was only 1.85% (one of 54
      patients), whereas over the same time period in the Mid D/S ratio group (average
      D/S ratio 1.08:1), all-cause mortality was 7.69% (three of 39 patients) and in
      the High D/S ratio group (average D/S ratio 1.32:1), all-cause mortality was
      8.82% (three of 34 patients). For the Low, Mid, and High D/S ratio groups,
      respectively: 1) average left ventricular ejection fractions increased 23.0%,
      20.1%, and 17.5%; 2) NYHA class declined 36.6%, 29.6%, and 29.6%; and 3) all
      cause hospitalizations, including terminal admissions, were reduced 85.7%, 82.6%,
      and 57.1% in the year following ECP therapy from the prior year. There were no
      adverse effects or withdrawals from the ECP therapy and no significant difference
      in sex-based outcomes. Consequently, ECP applied at low pressures and average D/S
      ratios of 0.7:1 under the new graduated pressure regimen is safe and effective in
      the treatment of CHF and produces a significant reduction in mortality, compared
      with the 8.5% annualized mortality of the Multicenter Automatic Defibrillator
      Implantation Trial II (MADIT II) (N=1232) of NYHA class II-III CHF and the 12.2%
      annual mortality of the Comparison of Medical Therapy, Pacing, and Defibrillation
      in Heart Failure (COMPANION) study (N=595) of NYHA class III-IV CHF. Lower
      pressures improve patient comfort and may encourage more CHF patients to seek
      treatment. The reduction in hospitalizations should significantly reduce the cost
      of treating CHF.

PMID- 15947537
TI  - Importance of in-hospital initiation of evidence-based medical therapies for
      heart failure: taking advantage of the teachable moment.

PMID- 15947538
TI  - Destination therapy: the future is arriving.

PMID- 15947541
TI  - Acute pulmonary hypertension secondary to right ventricular pacing in a patient
      with sinus node dysfunction and severe ischemic cardiomyopathy.
AB  - Right ventricular pacing has been associated with worsening symptoms of heart
      failure in patients with cardiomyopathy. We describe a patient with severe
      ischemic cardiomyopathy and sinus node dysfunction who developed acute worsening
      of pulmonary hypertension immediately after right ventricular pacing.

PMID- 15947542
TI  - Historical vignettes in heart failure.

PMID- 15947543
TI  - Gender and its effect in cardiovascular pharmacotherapeutics: recent
      considerations.
AB  - Gender differences in drug pharmacokinetics and pharmacodynamics have been
      recognized for some time. This issue has generally been ignored in clinical
      practice, despite there being ample evidence to suggest that gender can influence
      multiple aspects of pharmacokinetics. Gastric acid secretion, gastrointestinal
      blood flow, proportions of muscular and adipose tissue, the amount of drug
      binding proteins, gender-specific changes in the available amount of P450
      isozymes, physiologic and hormonal changes during the menstrual cycle, and
      differences in renal blood flow are several factors that may have some bearing on
      sex-related differences in pharmacokinetics. Furthermore, female-specific issues
      such as pregnancy, menopause, oral contraceptive use, and menstruation may
      independently influence drug metabolism and serve as confounders to the
      interpretation of gender differences in drug handling or effect. While gender
      related pharmacodynamic data are limited, evidence suggests that women are more
      prone to the development of torsade de pointes from proarrhythmic drugs such as
      quinidine or d-sotalol and have an increased cardiovascular risk with the use of
      digoxin. The specific risk:benefit ratio for individual cardiovascular
      medications should be more routinely considered in the context of gender.

PMID- 15947544
TI  - Venous thrombosis in inflammatory bowel disease.
AB  - Patients with inflammatory bowel disease (IBD) have a threefold increased risk of
      venous thrombosis, a major cause of morbidity and mortality. Although the exact
      mechanism explaining the initiation of thrombosis remains unclear, it is likely
      to be a multifactorial process. Reported abnormalities include activation of
      markers of the coagulation cascade, disturbed fibrinolysis and the activation of
      platelets. The contribution of thrombophilic disorders such as factor V Leiden,
      prothrombin gene mutations and hyperhomocysteinaemia are discussed, but their
      role in thrombosis associated with IBD has remained unclear. Recent research has
      examined elevated CD40, P-selectin levels and tissue factor-bearing microvesicles
      in venous thrombosis, and the relevance of these observations to IBD is reviewed.

PMID- 15947545
TI  - The promising future of proteomics in cancer diagnosis and treatment.
AB  - Cancer is a leading cause of death in developed countries. For most cancers, a
      patient's prognosis improves dramatically when the disease is detected at an
      early stage. Although advancements in imaging technology have dramatically
      improved early detection, many cancers go undetected until it is too late. As
      cancer develops, molecular changes occur before many of the current prognostic
      markers can be detected. Proteomics will be used to interrogate the protein
      milieu in serum and urine to detect molecular changes indicative of a disease
      state and will provide a cost-effective alternative to current diagnostic tools.

PMID- 15947546
TI  - Portal vein thrombosis: what is the role of genetics?
AB  - The aetiology of portal vein thrombosis (PVT) in adults is complex. Risk factors
      include local precipitating factors and acquired and inherited factors, an area
      in which there has been much recent progress. Although PVT in the absence of
      cirrhosis may be regarded as a somewhat different disorder to PVT in the presence
      of cirrhosis, in both cases most studies support a role of the prothrombin
      G20210A mutation. Some differences in risk factors observed between different
      studies may relate partly to referral patterns or study design, although
      individual patients may develop PVT as a result of differing combinations of risk
      factors. The demonstration of an inherited thrombophilic mutation in a subset of
      PVT may ultimately inform clinical management regarding the use and duration of
      anticoagulation therapy, although there is a need for evidence from randomized
      controlled clinical trial data.

PMID- 15947547
TI  - Cost-effectiveness of a 'score and scope' strategy for the management of
      dyspepsia.
AB  - OBJECTIVE: It is important to identify the best initial work-up in patients with
      uninvestigated dyspepsia because of its epidemiological and economical relevance.
      The objective of the study was to assess systematically the effectiveness and
      cost-effectiveness of invasive and non-invasive strategies for the management of
      dyspepsia. METHODS: A decision analysis was performed to compare prompt
      endoscopy, score and scope, test and scope, test and treat, and empirical
      antisecretory treatment. Published and local data on the prevalence of different
      diagnoses, rates of Helicobacter pylori infection, accuracy values of diagnostic
      tests, and effectiveness of drug treatments were used. The perspective of
      analysis was that of the public healthcare payer, and only direct costs were
      included, with a one-year post-therapy time horizon. The main outcome measure was
      cost per asymptomatic patient, valued in 2003 Euros. RESULTS: Endoscopy was found
      to be the most effective strategy for the management of dyspepsia (38.4%
      asymptomatic patients), followed by test and scope (35.5%), test and treat
      (35.3%), score and scope (34.7%), and empirical treatment (28.5%). Incremental
      cost-effectiveness ratios showed that score and scope was the most cost-effective
      alternative (483.17 Euros per asymptomatic patient), followed by prompt endoscopy
      (1396.85 Euros). Sensitivity analyses showed variations when varying the values
      of prevalence of duodenal ulcer, and the values of healing of functional
      dyspepsia with antisecretory and eradication drugs. There were no changes when
      varying the prevalence of H. pylori in dyspepsia. CONCLUSIONS: We would recommend
      stratifying patients by a score system, referring first to endoscopy those
      patients at higher risk of organic dyspepsia.

PMID- 15947548
TI  - An audit of informed consent in gastroscopy: investigation of a hospital's
      informed consent procedure in endoscopy by assessing current practice.
AB  - OBJECTIVE: To investigate, by assessing current practice, whether a UK general
      hospital's informed consent procedure in endoscopy was implemented for all
      patients, because informed consent is central to the proper conduct of endoscopic
      procedures. METHODS: A retrospective study of patients' medical notes, in which
      information written on the UK National Health Service (NHS) consent form and on a
      departmental leaflet on the gastroscopy procedure completed by the patient was
      assessed. Sampling began from 9 October 2003 until 100 patients were recorded.
      For each patient's record, a data collection sheet was completed. RESULTS: Of the
      67 patient records assessed (33 were unavailable), all contained the NHS consent
      form with signatures from the practitioner and patient. The departmental leaflet
      was present for only 31 patients, and of these, 20 had a signature from the
      patient and one leaflet had a signature from the practitioner. The multiple
      choice test was completed for 28 of the 31 departmental leaflets and full marks
      were awarded for 17 of 28. Although 11 patients answered one or more questions
      incorrectly, a discussion of the correct answers was only found in two records.
      CONCLUSION: To achieve improved performance, a training/induction programme
      should explain the informed consent procedure and its importance. This should be
      supported by 'booster' training sessions to avoid the emergence of bad practice.
      These sessions should take advantage of evidence-based medicine via feedback from
      audits and discussions of litigation cases. Departmental leaflets and NHS consent
      forms should also be provided in other languages.

PMID- 15947549
TI  - Proteomic analysis of differentially expressed proteins between metastatic and
      non-metastatic human colorectal carcinoma cell lines.
AB  - OBJECTIVES: To explore the expressions of metastasis-related proteins between
      metastatic LS174T and non-metastatic SW480 human colorectal carcinoma cell lines.
      METHODS: Two-dimensional gel electrophoresis (2-DE) was applied to separate the
      total proteins of cells. The silver-stained gels were analysed by 2-DE software
      Image Master 2D Elite. Selected differential protein spots were identified with
      peptide mass fingerprinting based on matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry and database searching. RESULTS: The protein
      endothelial cell growth factor 1 (platelet-derived), rhotekin protein (RTKN),
      septin 1, cyclin-dependent kinase 1, sialic acid binding Ig-like lectin 11,
      tyrosinase-related protein-2, translin-like protein, and DNA directed RNA
      polymerase II polypeptide J-related gene isoform 2 appeared in metastatic but
      were not detected in non-metastatic cell lines, whereas integrin-linked kinase
      associated protein phosphatase 2C isoform 2, MHC class I promoter binding
      protein, protein phosphatase 2A regulatory subunit B' (PR 53), carboxypeptidase
      A5, paired box transcription factor, zinc finger protein 79, and apolipoprotein B
      48 were detected in non-metastatic but were absent in metastatic cell lines. In
      addition, cyclin fold protein 1 variant A and pre-B-cell leukemia transcription
      factor 1 were lowly expressed in the non-metastatic cell line and were
      significantly upregulated in the metastatic cell line. These identified proteins
      were involved in cell growth, motility, invasion, adhesion, apoptosis and tumour
      immunity, which is associated with distinct aspects of tumour metastasis.
      CONCLUSIONS: These data are valuable for the identification of differentially
      expressed proteins involved in human colorectal carcinoma carcinogenesis and
      metastasis.

PMID- 15947550
TI  - Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in
      hepatopancreaticobiliary cancer.
AB  - OBJECTIVE: Hepatopancreaticobiliary cancers can be difficult to diagnose. Nuclear
      magnetic resonance (NMR) spectroscopy provides non-invasive information on
      phospholipid metabolism, and previous studies of liver tissue have highlighted
      changes in phospholipids in malignancy. We hypothesised that in-vitro NMR
      spectroscopy of human bile may provide independent diagnostic indices in cancer
      management through an assessment of the phospholipid content. DESIGN AND METHODS:
      Bile samples from 24 patients were collected at endoscopic retrograde
      cholangiopancreatography and from one subject at cholecystectomy. Thirteen
      patients had cancer: pancreatic carcinoma (eight), cholangiocarcinoma (three) and
      metastatic liver disease (two). The remaining 12 patients had non-malignant
      pathology. In-vitro proton (H) and phosphorus-31 (P) NMR spectra were obtained
      from all samples using an 11.7 Tesla NMR spectroscopy system. RESULTS:
      Complementary information was obtained from the H and P NMR spectra. Signals were
      assigned to phosphatidylcholine in both H and P NMR spectra. Phosphatidylcholine
      levels were significantly reduced in the bile from cancer patients when compared
      with bile from non-cancer patients (P=0.007). CONCLUSION: These preliminary
      studies suggest that H and P NMR spectroscopy of bile may be used to detect
      differences in phospholipid content between cancer and non-cancer patients. This
      may have implications for the development of novel diagnostic strategies in
      hepatopancreaticobiliary cancers. Further larger-scale studies are warranted.

PMID- 15947551
TI  - Prevalence of hyperhomocysteinaemia, activated protein C resistance and
      prothrombin gene mutation in inflammatory bowel disease.
AB  - BACKGROUND: Thromboembolic disease is a significant cause of morbidity and
      mortality in patients with inflammatory bowel disease (IBD). A hypercoagulable
      state exists in IBD that may involve many components of haemostasis and is
      closely linked to the disease pathogenesis. It has been proposed that
      microvascular thrombosis and infarction may trigger the underlying inflammatory
      process. AIM: To determine the prevalence of prothrombotic factors including
      hyperhomocysteinaemia, activated protein C (APC) resistance and prothrombin gene
      mutations as well as vitamin levels in the local IBD population. METHOD: A total
      of 68 patients (37 men and 31 women) attending the IBD clinic were enrolled into
      the study. Citrated and ethylenediamine tetraacetic acid blood samples were
      collected from all patients as well as from 30 controls. Homocysteine levels were
      measured using the IMX immunoassay. APC resistance was measured using an
      unmodified activated partial thromboplastin time-based clotting assay.
      Prothrombin mutations were determined using polymerase chain reaction with the HB
      gene factor II detection system. RESULTS: Mean homocysteine levels were
      significantly higher and APC resistance ratios significantly lower in IBD
      patients compared with controls. No significant difference was detected between
      patients with ulcerative colitis or Crohn's disease. There was no significant
      increase in the incidence of prothrombin mutation in IBD patients. IBD patients
      had lower vitamin B12 and higher serum folate levels than controls. CONCLUSION:
      High homocysteine and high serum folate may be associated with low vitamin B12
      levels in IBD patients. We did not find any association between a low APC ratio
      and the factor V Leiden mutation or high factor VIII levels. Both
      hyperhomocysteinaemia and a low APC ratio may contribute to an increased risk of
      thromboembolic disease in IBD patients.

PMID- 15947552
TI  - Causes of portal venous thrombosis in cirrhotic patients: the role of genetic and
      acquired factors.
AB  - OBJECTIVE AND METHODS: We compared frequencies of three common prothrombotic
      mutations (factor V Leiden, the G20210A mutation of the prothrombin gene, and
      homozygosity for C677T methylenetetrahydrofolate reductase) in 219 cirrhotic
      patients, 43 with and 176 without portal vein thrombosis (PVT). The following
      variables were related to PVT: prothrombin levels, platelet count, Child-Pugh
      classification, previous abdominal surgery, number of decompensation events, size
      of varices, red markers on varices, and sclerotherapy. All patients were followed
      up for a mean period of 18 months (range 10-30). RESULTS: Prothrombotic mutations
      were detected in 64 of the 219 cirrhotic patients (29.2%), at equal frequency in
      patients with or without PVT. At univariate analysis, PVT was associated with
      Child-Pugh classes B and C, signs of liver decompensation, large varices with red
      markings, sclerotherapy, and abdominal surgery. At multivariate analysis, PVT was
      associated with sclerotherapy [odds ratio (OR) 4.9, 95% confidence interval (CI)
      2.2-11] and previous surgery (OR 2.8, 95% CI 1.2-6.3). The combination of the two
      acquired factors increased the risk of PVT, whereas the combination of local with
      genetic defects did not. Only a single patient with genetic thrombophilia and
      without PVT at inclusion developed the complication during follow-up,
      concomitantly with the development of hepatocellular carcinoma. CONCLUSION: In
      cirrhotic patients prothrombotic mutations by themselves are not causative of
      PVT. Sclerotherapy and previous abdominal surgery favour the development of two
      thirds of cases of PVT; in the remaining cases the pathogenesis remains elusive.

PMID- 15947553
TI  - Serum hepatitis B virus DNA levels differentiating inactive carriers from
      patients with chronic hepatitis B.
AB  - OBJECTIVE: We compared serum hepatitis B virus (HBV)-DNA levels in different
      states of hepatitis B infection, and investigated whether there is an HBV-DNA
      value that can be used for differentiating inactive carriers from patients with
      hepatitis B e antigen (HBeAg)-negative chronic hepatitis. METHODS: A
      retrospective study using sera at a followed endpoint from 64 Japanese patients
      with chronic HBV infection seen in Kobe University Hospital between 1989 and
      2002. Sera of patients were assayed using a polymerase chain reaction-based
      assay. RESULTS: Genotype C was dominant (95.4%). Patients with chronic hepatitis
      with an elevation of the serum alanine aminotransferase (ALT) level had
      significantly higher HBV-DNA levels than patients with persistently normal ALT.
      For one time observation at a followed endpoint, the mean HBV-DNA level of HBeAg
      negative inactive carriers was significantly lower than that of HBeAg-negative
      chronic hepatitis patients (3.6+/-1.0 versus 4.8+/-1.5 log copies/ml, P<0.005).
      The use of a cutoff value of 4.5 or 5.0 log copies/ml misclassified 23 and 18% of
      HBeAg-negative inactive carriers and 50 and 55% of patients with HBeAg-negative
      chronic hepatitis. If testing were performed on two occasions with approximately
      a 4-month interval, the cutoff values of 4.5 and 5.0 log copies/ml would
      misclassify 20 and 10% of HBeAg-negative inactive carriers and 28.6 and 28.6% of
      patients with HBeAg-negative chronic hepatitis. CONCLUSIONS: The measurement of
      serum HBV DNA more than twice is useful for assessing chronic hepatitis B surface
      antigen carriers and confirms that 10 copies/ml may be an appropriate level of
      HBV for characterizing the inactive carrier state.

PMID- 15947554
TI  - Bilirubin response to corticosteroids in severe alcoholic hepatitis.
AB  - INTRODUCTION: There is little consensus on the management of alcoholic hepatitis,
      particularly with regard to corticosteroid therapy. We aimed to identify those
      patients who respond to corticosteroid therapy for alcoholic hepatitis. METHODS:
      We identified 37 patients with alcoholic hepatitis with a modified Maddrey's
      discriminant function of 32 or greater. We assessed their outcomes at 28 and 56
      days treatment after admission relative to their response to corticosteroid
      treatment. RESULTS: Corticosteroid treated patients experienced a change in the
      serum bilirubin concentration after 6-9 days of -23.0+/-4.7%. Overall, the
      mortality was 18.9 and 35.1% at 28 and 56 days. Response to corticosteroids was
      defined as a 25% fall in serum bilirubin after 6-9 days of treatment. The
      mortality of the non-responders was 36.8% and 57.9% at 28 and 56 days compared
      with 0% (P=0.0148) and 11.1% (P=0.0084) for corticosteroid responders.
      CONCLUSIONS: Patients with a 25% fall in bilirubin after 6-9 days of
      corticosteroid therapy have a significant and sustained improvement in outcome.

PMID- 15947555
TI  - Leukotriene inhibitors in combination with steroids: potential role in the
      development of primary bacterial peritonitis.
AB  - Leukotrienes play a role in inflammation, and their participation in airway
      inflammation and bronchoconstriction in patients with severe asthma can be
      ameliorated by a new class of drugs known as leukotriene modulators. The role of
      leukotrienes in increasing vascular permeability in experimental peritonitis and
      in inducing chemotaxis of inflammatory cells has recently been documented.
      Steroids have been incriminated in the development of bacterial translocation in
      animal models in association with the suppression of mucosal immunity. The
      development of spontaneous bacterial peritonitis is recognized in cirrhotic
      patients with ascites and in those with nephrotic syndrome. The onset of
      bacterial peritonitis in the absence of these predisposing conditions or other
      underlying cause, such as perforated viscus, is termed 'primary bacterial
      peritonitis', and has never been described in asthmatic patients. We present an
      asthmatic patient who developed primary bacterial peritonitis while receiving a
      leukotriene modulator in combination with prednisolone therapy. The hypothesis
      that leukotriene receptor blockade might predispose to the development of primary
      bacterial peritonitis in patients receiving steroid therapy is discussed.

PMID- 15947556
TI  - Primary sclerosing cholangitis in two brothers: report of a family with special
      emphasis on molecular HLA and MICA genotyping.
AB  - Immune mechanisms play a role in the pathogenesis of primary sclerosing
      cholangitis (PSC), as suggested by its association with certain HLA haplotypes.
      Genetic predisposition is supported by its occurrence in families, but data are
      scarce. Our aim is to report on two brothers with PSC, and to investigate HLA and
      MICA alleles in this family. The clinical, biochemical, radiological, and
      pathological findings in two brothers with PSC as well as in their sister and
      parents were reviewed. Molecular genotyping of HLA class II and MICA alleles was
      performed in all five family members. In two brothers, p-ANCA positive PSC was
      found. The youngest also had ulcerative colitis, and had evolved into cirrhosis
      at the age of 17 years. Their mother had positive p-ANCA and mild cholestatic
      changes. Their father and sister were unaffected. Both brothers were homozygous
      for the MICA*00801 allele, and were positive for the susceptibility HLA
      haplotypes DR3-DQ2 and DR6-DQ6. Their unaffected father and sister both carried
      the protective DR4 allele. The presence of PSC in two brothers, and the
      distribution of HLA haplotypes and MICA alleles, adds supportive evidence for an
      immunogenetic origin of PSC.

PMID- 15947557
TI  - Whipple's disease: a rare cause of haematemesis and melaena.

PMID- 15947564
TI  - Imaging for vesicoureteral reflux--is there a better way?

PMID- 15947565
TI  - Surgical removal of small renal tumors--going, going, gone?

PMID- 15947566
TI  - Alpha1 adrenoceptor subtypes and bladder function.

PMID- 15947567
TI  - Percutaneous, image guided urological procedures: barbarians at the gate.

PMID- 15947568
TI  - Widening the scope of erectile dysfunction risk associations.

PMID- 15947569
TI  - Update on chemotherapy for advanced bladder cancer.
AB  - PURPOSE: Recent years have seen several advances in the treatment of locally
      advanced and metastatic bladder cancer. We summarize the current state of the art
      for advanced bladder cancer treatment. MATERIALS AND METHODS: A comprehensive
      review of published, prospective phase II/III clinical trials and retrospective
      analyses of patients with advanced bladder cancer was performed. RESULTS:
      Adjuvant and neoadjuvant chemotherapeutic strategies around the time of radical
      cystectomy have been used to decrease the risk of subsequent metastatic disease.
      Although the benefit of adjuvant chemotherapy remains unproven, neoadjuvant
      chemotherapy is associated with a modest 5% to 6% absolute survival benefit in 2
      meta-analyses of the available data. Chemoradiation is feasible and effective in
      some patients, allowing bladder preservation with an acceptable risk of
      progression. Randomized, phase III data comparing methotrexate, vinblastine,
      doxorubicin and cisplatin chemotherapy to gemcitabine/cisplatin showed similar
      response proportions and overall survival with less toxicity in the
      gemcitabine/cisplatin arm. This has led to the widespread use of
      gemcitabine/cisplatin as first line chemotherapy for metastatic bladder cancer.
      The optimal agents and regimens for second line chemotherapy remain undefined.
      Similarly biological and targeted therapies for advanced bladder cancer remain
      investigational. CONCLUSIONS: Combination cisplatin based neoadjuvant
      chemotherapy may benefit patients with locally advanced bladder cancer.
      Gemcitabine/cisplatin has replaced methotrexate, vinblastine, doxorubicin and
      cisplatin as the regimen of choice in patients with good renal function. The
      optimal regimens for the medically unfit patient and second line chemotherapy
      remain undefined. The development of targeted therapies, less toxic regimens and
      improved cytotoxic agents are necessary to improve outcomes.

PMID- 15947570
TI  - Is orthotopic bladder replacement the new gold standard? Evidence from a
      systematic review.
AB  - PURPOSE: In this systematic review we determined whether the outcome of
      orthotopic bladder replacement is superior to that of continent and incontinent
      urinary diversion. MATERIALS AND METHODS: We searched MEDLINE, PubMed, EMBASE,
      CINAHL and the Cochrane Library from January 1990 to January 2003. A total of
      3,370 abstracts were reviewed, including all types of studies from prospective,
      randomized, controlled studies to small, retrospective series. All relevant
      articles with at least 10 patients and a mean followup of at least 1 year were
      retrieved. There were no language restrictions. NonEnglish articles were
      translated. Comparisons were made between the major surgery types, including
      ileal conduit, continent diversion, bladder reconstruction and bladder
      replacement. All studies were scored using a predetermined quality assessment
      checklist to assess internal validity (bias and confounding) and external
      validity. RESULTS: A total of 405 studies met inclusion criteria. There were 32
      prospective and 373 retrospective studies describing a total of 32,795 patients.
      The majority of studies were incompletely or poorly described and outcomes were
      often not defined. When they were defined, definitions varied. In clinical
      outcomes ileal conduit diversions had the lowest operative complications rate but
      highest reported postoperative morbidity. They also had a higher reported
      incidence of symptomatic urinary tract infections. The rates of postoperative
      morbidity, mortality and need for reoperation varied widely among studies even
      for the same procedure. Of physiological outcomes metabolic acidosis was the most
      commonly reported metabolic complication in patients with various urinary
      diversions. The quality of the reported literature was poor. There were no
      studies of the health economic implications of performing 1 type of surgery vs
      another type. CONCLUSIONS: While enthusiasts regard orthotopic bladder
      replacement as the new gold standard when lower urinary tract function must be
      replaced, the level and quality of current evidence are poor. The immediate
      concern must be to rectify this paucity of evidence with well designed and well
      reported prospective studies, ideally in a randomized setting, comparing the
      various major forms of urinary diversion and bladder replacement surgery.

PMID- 15947571
TI  - How little is enough? The evidence for post-vasectomy testing.
AB  - PURPOSE: Post-vasectomy semen analysis (PVSA) is the traditional method of
      confirming sterility after vasectomy. However, PVSA protocols vary in the end
      points accepted, and the number and timing of tests. In this systematic review we
      make evidence based recommendations on the appropriate PVSA protocol. MATERIALS
      AND METHODS: Databases (MEDLINE, Current Contents, Cochrane Library and EMBASE)
      were searched up to and including March 2003. Studies were included if they dealt
      with post-vasectomy testing and contained data on at least 1 of the time or
      number of ejaculations to azoospermia, pregnancy, repeat vasectomy and
      histological analysis of vas specimens. RESULTS: A total of 56 studies were
      included in the review. Time to achieve azoospermia was variable, although the
      median incidence of patients with azoospermia was consistently more than 80%
      after 3 months and after 20 ejaculations. A small percent of patients (14,845 or
      1.4%) demonstrated persistent nonmotile sperm, although some of them eventually
      achieved azoospermia. The reappearance of nonmotile sperm was reported in 7
      studies, occurring up to 22 months after vasectomy. CONCLUSIONS: The evidence
      supports a PVSA protocol with 1 test showing azoospermia after 3 months and 20
      ejaculations. If the sample is positive, periodic testing can continue until
      azoospermia is achieved. Patients with persistent nonmotile sperm in low numbers
      could be given cautious assurance of success. No evidence was located to support
      histological testing of the excised vas deferens.

PMID- 15947572
TI  - Thomas Annandale and the first report of successful orchiopexy.
AB  - PURPOSE: We investigate the surgeon and factors behind the first report of
      successful orchiopexy. MATERIALS AND METHODS: We reviewed the first reports of
      orchiopexy, and the work and writings concerning Thomas Annandale and the time in
      which he practiced. RESULTS: Annandale was a surgeon in Edinburgh, Scotland, in
      the late 19th century. In 1877 he successfully brought down an ectopic testicle
      in a 3-year-old boy. This first reported successful orchiopexy was due in large
      part to Lister's antiseptic technique. CONCLUSIONS: Annandale performed the first
      successful orchiopexy by integrating the surgical and antiseptic ideas of his
      predecessors and contemporaries.

PMID- 15947573
TI  - Laparoscopic partial versus total adrenalectomy for aldosterone producing
      adenoma.
AB  - PURPOSE: Laparoscopic surgery has become a standard method for adrenal treatment.
      Primary hyperaldosteronism is known to be frequently characterized by multiple
      adrenal lesions. The indication of laparoscopic partial or total adrenalectomy in
      patients with aldosterone producing adenoma (APA) remains controversial. We
      performed the 2 procedures and compared the outcomes of these 2 operations
      retrospectively. MATERIALS AND METHODS: A total of 92 patients with primary
      hyperaldosteronism were laparoscopically treated at our institution from 1995 to
      2004. A total of 29 patients underwent partial adrenalectomy or enucleation,
      while unilateral total adrenalectomy was performed in 63. A single pathologist
      examined the number and histopathological characteristics of APAs. Postoperative
      median followup was 60.3 and 29.3 months, respectively. RESULTS: Laparoscopic
      adrenalectomies were successfully performed in each group, although the partial
      type had fewer ports and shorter operative time. All 63 patients with total
      adrenalectomy showed recovery from hypertension, suppressed plasma renin activity
      and high plasma aldosterone. Two of 29 patients with partial adrenalectomy or
      enucleation still experienced hypertension with high plasma aldosterone. Of the
      63 extirpated specimens 17 adrenals (27.0%) demonstrated multiple space occupying
      lesions along with the main APA. CONCLUSIONS: Primary hyperaldosteronism is
      highly associated with multiple adrenal space occupying lesions. The risk-to
      benefit ratio must be carefully weighed against the potential advantage of
      partial adrenalectomy. We chose total laparoscopic adrenalectomy in patients with
      unilateral APA and primary hyperaldosteronism.

PMID- 15947574
TI  - The accuracy of 250 fine needle biopsies of renal tumors.
AB  - PURPOSE: In some cases of uncertain lesions in the kidney it would be helpful to
      perform biopsies for preoperative histopathological evaluation. In this study we
      evaluated the accuracy of and the impact on tumor management of core biopsy for
      histopathological evaluation of small solid renal masses. MATERIALS AND METHODS:
      After radical or partial nephrectomy 250 renal tumor biopsies were performed in
      50 patients. All biopsies were performed by 1 urologist after preparation of the
      kidney ex situ on back table visually guided. Formalin fixed paraffin embedded
      biopsies were evaluated by 1 pathologist. RESULTS: In 49 of 50 cases (98%) we
      could define the malignant behavior of the tumor when performing 1 central and 4
      peripheral biopsies of each tumor. In 85.2% the grading was correctly defined. A
      benign lesion was revealed in 4 cases (8%, all oncocytoma). In renal tumors 4 cm
      or smaller in diameter the accuracy of 1 central and 1 peripheral biopsy each
      regarding definition of tumor origin, tumor grading and cell type/growth pattern
      was 96% and 95.5%, 84% and 84.4%, and 87.5% and 89.5%, respectively. In renal
      tumors more than 4 cm in diameter the accuracy was 100% and 98.1%, 85% and 94.3%,
      and 71.4% and 88.7%, respectively. CONCLUSIONS: Core biopsy of renal lesions is
      accurate enough for histopathological evaluation and determination of therapeutic
      procedure. Additionally, biopsy could be used for identifying benign renal lesion
      for observation.

PMID- 15947575
TI  - Fibrin glue v sutured bolster: lessons learned during 100 laparoscopic partial
      nephrectomies.
AB  - PURPOSE: Laparoscopic partial nephrectomy (LPN) is performed with marked
      technical variations. We defined the limits of sutureless LPN and determined
      which closure technique is best in a particular situation. MATERIALS AND METHODS:
      During 100 consecutive LPNs fibrin glue products were used for closure in the
      first 75 (group 1) and sutured bolsters were applied when the collecting system
      (CS) or renal sinus was entered in the final 25 (group 2). RESULTS: In groups 1
      and 2 hand assisted laparoscopy was used in 72% vs 40% of cases and hilar
      clamping was used in 27% vs 92%, respectively. Mean tumor size was 25 vs 26 mm,
      tumor depth was 11 vs 13 mm, distance to the renal sinus was 9 vs 5 mm, operating
      room time was 185 vs 210 minutes, estimated blood loss was 398 vs 247 cc and
      hospital stay was 2.9 vs 2.6 days in groups 1 and 2, respectively. Overall
      postoperative hemorrhage and urine leakage occurred in 9% and 2% of patients,
      respectively. Tumors associated with postoperative hemorrhage/leakage tended to
      be larger (35 vs 24 mm, p = 0.007) and closer to the renal sinus (0.5 vs 8.2 mm,
      p = 0.02). Postoperative hemorrhage or urine leakage occurred in 41% of the 17
      patients in group 1 with CS or renal sinus entry but in only 2 of the 58 (3.4%)
      without entry (p <0.0001). In group 2 hemorrhage/leakage occurred in 11% of the
      18 patients with CS or renal sinus entry (vs same subset in group 1, p = 0.04).
      CONCLUSIONS: LPN with closure using fibrin glue products provides adequate
      hemostasis when the CS or renal sinus is not entered. When the CS or renal sinus
      is entered, a sutured bolster is recommended.

PMID- 15947576
TI  - 100-minute retroperitoneoscopic radical nephrectomy: a new retroperitoneal
      approach with a hand assisted method.
AB  - PURPOSE: A new approach for retroperitoneoscopic radical nephrectomy is
      introduced. The point of our surgical method is the application of a combination
      of hand assistance and pure laparoscopic procedures with appropriate surgical
      steps via the retroperitoneal approach. In our early series we had good surgical
      results and we completed radical nephrectomy in about 100 minutes using this
      procedure. MATERIALS AND METHODS: A total of 20 consecutive patients with renal
      cell carcinoma (cT1-2) who were operated on with this surgical method were
      analyzed. Surgical procedures occurred in 5 steps. In step 1 the retroperitoneal
      space was created manually from a pararectal incision at the umbilicus level. In
      step 2 the lateroconal fascia was incised and the renal hilar area was exposed
      with hand assistance. In step 3 hilar dissection was performed by pure
      laparoscopic procedure with another surgical instrument inserted from the hand
      device. Step 4 involved the application of hand assistance again for the quick
      mobilization of the kidney and adrenal gland. In step 5 the intact surgical
      specimen was retrieved from the hand device. RESULTS: Mean operative time and
      estimated blood loss were 103 +/- 21 minutes (range 70 to 145) and 49 +/- 85 ml
      (range 5 to 360), respectively. Mean days to oral intake and ambulation were 1.0
      and 1.1, respectively. Operative times of the steps of hilar dissection and
      mobilization of the kidney and adrenal were shorter than in other series
      performed by standard retroperitoneoscopic radical nephrectomy. Major
      complications were not experienced. At this point, no metastasis has been
      experienced. CONCLUSIONS: Our surgical method may have the benefits of the
      retroperitoneal approach and hand assistance. The retroperitoneoscopic hand
      assisted method may be another important option in the 3 major approaches for
      laparoscopic radical nephrectomy, although longer-term followup is clearly
      required.

PMID- 15947577
TI  - Progression and long-term survival after simple enucleation for the elective
      treatment of renal cell carcinoma: experience in 107 patients.
AB  - PURPOSE: We present our findings in a series of T1a renal cell carcinoma treated
      with elective simple enucleation, specifically reporting the incidence of local
      recurrence, and progression-free and disease specific survival rates. MATERIALS
      AND METHODS: A total of 107 patients who underwent elective nephron sparing
      surgery performed with simple enucleation from January 1989 to December 2000 were
      studied retrospectively. None of the patients had preoperative or intraoperative
      suspicion of positive nodes. All patients were free from distant metastases
      before surgery (M0). Patient status was last evaluated in July 2004. Mean
      (median, range) followup was 88.3 (84, 44 to 175) months. RESULTS: Pathological
      review according to the 2002 TNM classification showed that 95% (102 of 107) of
      tumors were pT1a, 4% (4 of 107) pT1b and 1% (1 of 107) pT3a. Mean (SD, median,
      range) tumor greatest dimension was 2.7 (0.93, 2.5, 0.6 to 5) cm. None of the
      patients died in the immediate postoperative period (within the first 30 days).
      There were no major complications such as bleeding and urinary leakage/urinoma
      requiring reoperation. The 5 and 10-year cancer specific survival was 99% and
      97.8%, respectively. The 5 and 10-year progression-free survival was 98.1% and
      94.7%, respectively. Overall 3 patients had disease progression (2.8%) of whom 2
      (1.9%) were local recurrence, 1 alone and 1 associated with distant metastases
      diagnosed 12 months earlier. CONCLUSIONS: Simple tumor enucleation is a safe and
      acceptable approach for elective nephron sparing surgery. It provides excellent
      long-term progression-free and cancer specific survival rates, and is not
      associated with an increased risk of local recurrence compared with partial
      nephrectomy.

PMID- 15947578
TI  - Long-term followup of patients with renal cell carcinoma treated with radio
      frequency ablation with curative intent.
AB  - PURPOSE: We defined the role of radio frequency ablation in the treatment of
      renal cell carcinoma. MATERIALS AND METHODS: A total of 16 patients with biopsy
      proven renal cell carcinoma were treated with radio frequency ablation in an
      outpatient setting and followed for a minimum of 4 years. RESULTS: Of the 16
      patients 5 died before 4 years of followup of unrelated causes. All except 1
      tumor was successfully treated. All patients with exophytic tumors were
      successfully treated. CONCLUSIONS: Radio frequency ablation of exophytic renal
      cell carcinomas less than 5 cm in diameter is effective in eradicating the tumor
      and comparable to surgical extirpation at 4 years.

PMID- 15947579
TI  - Use of the novel marker BLCA-1 for the detection of bladder cancer.
AB  - PURPOSE: Bladder cancer specific nuclear structural alterations have been
      identified. We examined the expression pattern of one of these proteins, BLCA-1,
      in tissue and urine samples from individuals with bladder cancer as well as in
      samples from normal controls. MATERIALS AND METHODS: BLCA-1 sequence data were
      used to produce antibodies to this protein, which were used in immunoblot and
      enzyme-linked immunosorbent assays. RESULTS: BLCA-1 was detectable in tissue from
      patients with bladder cancer but not in normal adjacent areas of the bladder or
      in normal donor bladder tissue. This protein was also detectable in the urine of
      patients with bladder cancer by immunoblot and immunoassay. Using a cutoff of
      0.025 optical density units (absorbance value) BLCA-1 was detected in 20 of 25
      urine samples from patients with bladder cancer but in only 6 of 46 normal, high
      risk, prostate or renal cancer samples tested, resulting in a test with 80%
      sensitivity and 87% specificity. Expression of this protein did not appear to
      correlate with tumor grade. CONCLUSIONS: This research indicates that BLCA-1 is a
      urine based marker of bladder cancer which may be useful for the detection of
      this disease.

PMID- 15947580
TI  - Permeation of hypericin in spheroids composed of different grade transitional
      cell carcinoma cell lines and normal human urothelial cells.
AB  - PURPOSE: We investigated the importance of E-cadherin expression on the selective
      accumulation of hypericin in superficial bladder cancer after intravesical
      instillation. MATERIALS AND METHODS: Spheroids obtained from a panel of 3
      transitional cell carcinoma cell lines, namely J-82, RT-4 (American Type Culture
      Collection, Manassas, Virginia) and RT-112 (German Collection of Micro-organisms
      and Cell Cultures, Braunschweig, Germany), and normal human urothelial (NHU)
      cells were incubated with hypericin. Accumulation was examined with fluorescence
      microscopy. Immunohistochemical staining was used to assess E-cadherin
      expression. RESULTS: Immunohistochemical staining showed E-cadherin expression in
      NHU (++), RT-112 (+) and RT-4 (+) spheroids, whereas E-cadherin expression was
      absent in J-82 spheroids. The highest intraspheroidal hypericin accumulation was
      observed in transitional cell carcinoma spheroids, whereas limited permeation was
      seen in NHU spheroids. Taken together the data point to an inverse relationship
      between E-cadherin expression and the permeation of hypericin throughout a 3
      dimensional cellular matrix. CONCLUSIONS: Loss of E-cadherin expression
      correlates with loss of intercellular adhesion, tight junction formation and
      enhanced paracellular transport. The data show that E-cadherin hampers the
      permeation of hypericin in spheroids and the loss of intercellular adhesion,
      present in superficial bladder cancer lesions, can be associated with enhanced
      hypericin permeation. Therefore, E-cadherin expression seems to have a pivotal
      role in the selective uptake of hypericin after intravesical instillation in
      human bladders.

PMID- 15947581
TI  - Clinical evaluation of serum p53 antibodies in patients with upper urinary tract
      tumors.
AB  - PURPOSE: We retrospectively assessed the clinical significance of anti-p53
      antibody (S-p53Ab) status in the serum of patients with upper urinary tract
      tumors. MATERIALS AND METHODS: Enzyme-linked immunosorbent assay was used to
      analyze S-p53Abs in 63 upper urinary tract tumors. Its incidence and clinical or
      pathological background were analyzed in comparison with 80 bladder tumors.
      RESULTS: The prevalence of S-p53Abs in patients with upper urinary tract tumors
      was higher than that in patients with bladder tumors (27.0% vs 17.5%).
      Especially, 34.8% of patients showed positive S-p53Abs in invasive upper urinary
      tract tumors (pT1 or more). In upper urinary tract tumors the prevalence of S
      p53Abs significantly correlated with higher grade (p <0.01), higher stage (p =
      0.02), positive lymph nodes (p = 0.03) and p53 nuclear accumulation (p <0.01).
      However, disease specific survival after nephroureterectomy did not differ
      between patients with negative and positive S-p53Abs. CONCLUSIONS: Our data
      suggest the possibility of the clinical application of S-p53Abs, especially for
      the detection of high grade or high stage tumors in the upper urinary tract.
      However, the usefulness of S-p53Abs as prognostic marker seems to be extremely
      limited in patients with urothelial tumors.

PMID- 15947582
TI  - Adjuvant intravesical treatment of superficial bladder cancer with a standardized
      mistletoe extract.
AB  - PURPOSE: Adjuvant intravesical immunotherapy with bacillus Calmette-Guerin (BCG)
      for noninvasive superficial bladder cancer has been shown to decrease tumor
      recurrence significantly. However, serious local and systemic side effects of
      this treatment have promoted the use of other immunoactive substances, which to
      date have failed to show efficacy equal to that of BCG immunotherapy. MATERIALS
      AND METHODS: In the current phase I/II clinical trial an aqueous mistletoe
      extract standardized to mistletoe lectin was administered intravesically to 30
      patients with superficial urothelial bladder carcinoma. About 4 weeks after
      transurethral resection each patient received 6 instillations at weekly intervals
      of 50 ml extract with mistletoe lectin concentrations between 10 and 5,000 ng/ml,
      which was retained in the bladder for 2 hours. Three patients per group received
      a dose, which was then doubled in the next group. Clinical followup consisted of
      examinations with cystoscopy, cytology and random biopsies. To detect cytokines
      and tumor necrosis factor-p75 receptor venous blood and urine samples were taken
      before instillation, and 2, 6 and 24 hours thereafter. RESULTS: The tolerability
      of intravesically administered mistletoe extract was good at all applied
      concentrations. None of the patients had local or systemic side effects according
      to WHO classification 1-4. Within the 12-month observation time study patients
      with pTa G2 and pT1 G2 tumors showed a recurrence rate of 33%, comparable to that
      in a local historical control group of patients with equal stage and grade who
      were treated with adjuvant BCG. Comparison of urine cytokine levels before
      instillation, and 2, 6 and 24 hours thereafter brought about no significant
      alterations in all measured cytokines. CONCLUSIONS: From these results it is
      concluded that standardized mistletoe extract could be a potential alternative
      adjuvant therapy for superficial bladder cancer. Nevertheless, the optimal
      intravesical treatment regimen has yet to be defined.

PMID- 15947583
TI  - Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for
      histologically proven lymph node positive bladder cancer.
AB  - PURPOSE: We gained insight into the effect of neoadjuvant chemotherapy and
      subsequent surgery in patients with bladder cancer with tumor positive lymph
      nodes. MATERIALS AND METHODS: A total of 52 patients with histologically proven
      positive lymph nodes (by lymph node dissection or aspiration cytology) were
      treated with chemotherapy and post-chemotherapy surgery in case of partial or
      complete response. We evaluated response in the primary tumor and lymph nodes,
      long-term clinical outcome, and clinicopathological features potentially
      predictive of survival. RESULTS: Complete response, partial response and
      stable/progressive disease were attained in 29%, 57% and 14%, and resulted in a 5
      year survival of 42%, 19% and 0%, respectively. Objective response (HR 4.1),
      especially complete response (HR 8.0), was independently associated with
      survival. The prognostic values of lymph node status and bladder tumor status
      after methotrexate, vinblastine, doxorubicin and cisplatin were evaluated
      separately. A tumor negative bladder combined with tumor negative nodes were
      associated with improved survival (HR 4.4) as was a tumor negative lymph node
      region in the presence of residual bladder disease (HR 2.8). All patients with
      post-chemotherapy tumor positive nodes died within 2 years. In resected specimens
      residual disease was found in 4 of 15 clinically complete responders while no
      tumor could be detected in 3 of 29 clinically assessed as partial responders.
      CONCLUSIONS: Response to chemotherapy is associated with improved survival, and
      our data suggest that lymph node status after methotrexate, vinblastine,
      doxorubicin and cisplatin is more important than local tumor status in this
      aspect. In the absence of reliable noninvasive methods, post-chemotherapy surgery
      in this series was the most adequate method of response evaluation and in limited
      partial responders led to long-term progression-free survival.

PMID- 15947584
TI  - Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of
      patients with carcinoma in situ of the bladder: a meta-analysis of the published
      results of randomized clinical trials.
AB  - PURPOSE: We determined the short-term and long-term efficacy of bacillus Calmette
      Guerin (BCG) and chemotherapy in the treatment of patients with carcinoma in situ
      (CIS). MATERIALS AND METHODS: A meta-analysis was performed on published results
      of randomized clinical trials comparing intravesical BCG to intravesical
      chemotherapy. RESULTS: Nine randomized trials including 700 patients with CIS
      compared BCG to either mitomycin C (MMC), epirubicin, adriamycin, or sequential
      MMC/adriamycin. Of 298 patients on BCG 203 (68.1%) had a complete response
      compared with 158 of 307 patients on chemotherapy (51.5%), a reduction of 47% in
      the odds of nonresponse on BCG (OR 0.53, p =0.0002). Based on a median followup
      of 3.6 years, 161 of 345 patients on BCG (46.7%) had no evidence of disease
      compared with 93 of 355 patients on chemotherapy (26.2%), a reduction of 59% in
      the odds of treatment failure on BCG (OR 0.41, p <0.0001). Although the long-term
      benefit of BCG was smaller in trials with MMC, BCG was superior to MMC in trials
      with maintenance BCG (OR 0.57, p =0.04). The reduction of 26% in the risk of
      progression on BCG (p =0.20) is consistent with the reduction of 27% (p =0.001)
      previously reported in a larger superficial bladder cancer meta-analysis.
      CONCLUSIONS: Intravesical BCG significantly reduces the risk of short and long
      term treatment failure compared with intravesical chemotherapy. Therefore, it is
      considered to be the intravesical agent of choice in the treatment of CIS.

PMID- 15947585
TI  - Radical cystectomy for primary neuroendocrine tumors of the bladder: the
      university of southern california experience.
AB  - PURPOSE: Primary neuroendocrine tumors of the bladder are rare and they include
      small and large cell variants. We reviewed our experience with treating these
      tumors with radical cystectomy to evaluate their histopathological
      characteristics and clinical outcomes. MATERIALS AND METHODS: From August 1971 to
      June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer
      at our institution, of whom 25 (1.2%) had neuroendocrine tumors of the bladder,
      including small cell carcinoma in 20 and large cell carcinoma in 5. Pure
      neuroendocrine-type histology was identified in 16 cases, including 1 with small
      and large cell features, while the remaining 9 had mixed histology, that is
      transitional cell carcinoma in 8 and adenocarcinoma in 1. Multi-agent
      chemotherapy was administered to 14 patients. RESULTS: Median patient age was 68
      years (range 40 to 82) and 19 patients were male (76%). A total of 19 patients
      (76%) had lymph node involvement, of whom 2 had small liver metastases found
      intraoperatively, while only 4 (16%) had organ confined tumors and 2 (8%) had
      extravesical, node negative disease. These tumors tended to have a flat,
      ulcerative gross appearance with lymphovascular invasion, carcinoma in situ and
      necrosis present microscopically. Median followup was 11.8 years (range 18 days
      to 15.1 years). Five-year overall and recurrence-free survival was 10% and 13%,
      respectively. There was no significant survival difference between small and
      large cell carcinoma. Mixed histologies tended to do better than pure
      neuroendocrine tumors, although this did not attain statistical significance (p =
      0.064). Patients receiving multimodality therapy had significantly better overall
      (p = 0.051) and recurrence-free (p = 0.003) survival than those treated with
      cystectomy alone. CONCLUSIONS: Neuroendocrine tumors of the bladder usually
      present with advanced pathological stage and portend a poor prognosis. Adjuvant
      chemotherapy protocols may provide improved survival compared with cystectomy
      alone.

PMID- 15947586
TI  - Local recurrence after cystectomy and survival of patients with bladder cancer: a
      population based study in greater amsterdam.
AB  - PURPOSE: We determined retrospectively in a population based study the survival
      of patients with bladder cancer and the local recurrence rate (LRR) after
      cystectomy. MATERIALS AND METHODS: All patients with bladder cancer diagnosed
      between 1988 and 2001 (vital status updated until September 2003) were selected
      from the Amsterdam Cancer Registry, which covers a population of 2.84 million
      individuals. For all patients who underwent cystectomy between 1988 and 1997 at
      18 participating hospitals information on local recurrence and vital status was
      collected from the medical records. RESULTS: Five-year relative survival in all
      8,321 bladder cancer cases combined was 75%. For clinical stage 0-a this was 99%,
      decreasing to 85% for stage 0-is and 82% for stage I, and to 44%, 28% and 9% for
      stages II to IV, respectively. Five-year relative survival after cystectomy was
      81%, 44% and 23% for stages II to IV, respectively. The LRR after cystectomy was
      19% in all 566 cases and all institutions combined. The LRR increased with higher
      pT stage and it achieved 11%, 23% and 31% for stages II to IV, respectively. It
      was slightly lower at oncological centers than at community hospitals (18% vs
      20%, not significant). CONCLUSIONS: Survival is higher than the European average
      but below the value in the United States. Only 1 of 3 stages II-III cases was
      treated with cystectomy. Relatively high stage specific survival is experienced
      after cystectomy despite local recurrence in 1 of 5 patients.

PMID- 15947587
TI  - Prognostic significance of lymphovascular invasion of bladder cancer treated with
      radical cystectomy.
AB  - PURPOSE: We determined the prognostic significance of lymphovascular invasion
      (LVI) in patients treated for invasive transitional cell carcinoma of the bladder
      with radical cystectomy. MATERIALS AND METHODS: From August 1971 to June 2004,
      2,005 patients underwent radical cystectomy for primary bladder cancer with
      intent to cure. All patients with nontransitional cell carcinoma histology,
      palliative procedures, unknown lymphovascular status, less than pT1 pathological
      stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were
      excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%)
      had LVI. RESULTS: Median followup was 11.0 years (range 8 days to 23.2 years).
      Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence
      free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in
      patients without LVI was 74% compared with 42% in those with LVI (p <0.0001).
      Similarly 10-year overall survival was 43% in patients without LVI compared with
      18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and
      lymph node positive pathological subgroups survival outcomes were significantly
      worse if LVI was present. Although a trend was observed, LVI status was not
      statistically significant in patients with extravesical node negative disease.
      Stepwise Cox regression analysis revealed that pathological subgroup (organ
      confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p =
      0.0004) were independent prognostic variables for recurrence-free and overall
      survival. CONCLUSIONS: Lymphovascular invasion appears to be an important and
      independent prognostic variable in patients with invasive bladder cancer treated
      with radical cystectomy. LVI status should be determined in cystectomy specimens,
      which may provide further risk stratification in patients following radical
      cystectomy.

PMID- 15947588
TI  - Bladder cancer risk following primary and adjuvant external beam radiation for
      prostate cancer.
AB  - PURPOSE: Increased rates of secondary bladder malignancies have been reported
      after external beam radiation therapy (EBRT) for gynecological malignancies with
      relative risks of 2 to 4. This study was designed to determine if there was an
      increase in bladder cancer after EBRT for prostate cancer. MATERIALS AND METHODS:
      We retrospectively reviewed the Mayo Clinic Cancer Registry for patients who
      received EBRT for prostate cancer (1980 to 1998). Patients diagnosed with bladder
      cancer were identified. Comparative incidence rates were obtained from the
      national Surveillance, Epidemiology and End Results database. Subset analysis
      included patients treated with adjuvant radiation and those residing locally.
      Medical histories of patients with bladder cancer were reviewed. RESULTS: A total
      of 1,743 patients received EBRT for prostate cancer at our institution. In more
      than 12,353 man-years of followup no increase in bladder cancer risk was
      encountered. Subset analysis of men who received adjuvant radiation demonstrated
      that the relative risk of bladder cancer was increased but was not statistically
      significant. When the analysis was restricted to patients residing in the local
      area, the number of patients in whom subsequent bladder cancer developed was
      similar to Surveillance, Epidemiology and End Results rates. However, in the
      adjuvant radiation subset there was a statistically significant increase in
      subsequent bladder cancer. Patients in whom bladder cancer develops after EBRT
      often present with low grade disease but many have recurrence and progression.
      CONCLUSIONS: This retrospective review suggests there is not evidence of
      increased risk of bladder cancer after radiation therapy, assuming unbiased
      followup and complete ascertainment of cases. The natural history of bladder
      cancer in this population does not seem to be altered by a history of radiation.

PMID- 15947593
TI  - Initial experiences with real-time elastography guided biopsies of the prostate.
AB  - PURPOSE: Based on our first experiences with real-time elastography in the field
      of prostate diagnostics we evaluate its usefulness for biopsy guidance for
      prostate cancer detection. MATERIALS AND METHODS: After imaging with conventional
      B-mode ultrasound in conjunction with real-time elastography 404 men underwent
      systematic sextant biopsy. RESULTS: Overall prostate cancer was found in 151 of
      404 cases (37.4%). In 127 of 151 cases (84.1%), prostate cancer was detected
      using real-time elastography as an additional diagnostic feature. CONCLUSIONS:
      The results show that it is possible to detect prostate cancer with a high degree
      of sensitivity using real-time elastography in conjunction with conventional
      diagnostic methods for guided prostate biopsies.

PMID- 15947594
TI  - Clinical and pathological characteristics of unstageable prostate cancer:
      analysis of the CaPSURE database.
AB  - PURPOSE: The new and older clinical staging systems for prostate cancer overlook
      a group of patients in whom abnormal digital rectal examinations (DREs) do not
      correlate with prostate biopsy findings. These cases are clinically unstageable.
      We evaluated the prevalence and pathological characteristics of these patients
      and stratified them into the 1997 American Joint Committee on Cancer clinical
      staging categories. MATERIALS AND METHODS: Using the CaPSURE database, a
      longitudinal disease registry of patients with various stages of prostate cancer,
      the unstageable cohort was identified. The postoperative pathological stage
      distribution of the unstageable cohort was used to assign the appropriate
      preoperative clinical stages in retrograde fashion. Pearson product moment
      correlation was used to establish the best clinical stage for this unstageable
      group. RESULTS: A total of 5,543 patients with recorded DREs were evaluated, of
      whom 2,610 (47%) had an isolated unilateral abnormality on DRE. A total of 235
      patients (9%) had prostate needle biopsies positive only on the contralateral
      side, yielding an unstageable prevalence of 4.2%. Of the cohort 102 patients
      (44%) underwent radical prostatectomy and 96 had adequate pathological staging
      data available for review and correlation. Pathological staging revealed pT2a
      cancers in 26%, pT2b in 53%, pT3a in 19%, pT3b and pT0 in 1% of patients. This
      distribution indicated that the unstageable cohort correlated most precisely with
      clinical stage T1c (r = 0.99). CONCLUSIONS: Thus, the prevalence of unstageable
      prostate cancer is low but significant and it can be accurately classified into
      clinical stage T1c.

PMID- 15947595
TI  - Comparison of screen detected and clinically diagnosed prostate cancer in the
      European randomized study of screening for prostate cancer, section rotterdam.
AB  - PURPOSE: This report provides a comparison of characteristics detected in the
      screening and control arms of the European Randomized study of Screening for
      Prostate Cancer, section Rotterdam. MATERIALS AND METHODS: Between December 1993
      and January 1999, 35,148 men 55 to 74 years old were randomized to European
      Randomized study of Screening for Prostate Cancer Rotterdam, including 17,635 in
      the screening arm and 17,513 in the control arm. Prostate specific antigen
      testing, digital rectal examination, transrectal ultrasound and sextant biopsies
      were offered to all participants in the screening arm according to 2 algorithms.
      All screening detected cancers and cancers found in the control arm were
      evaluated at the same cutoff point, that is January 1, 2003. To identify prostate
      cancer cases in the control arm yearly linkage was performed with the Rotterdam
      Cancer Registry database. Followup information was collected by chart review.
      RESULTS: By January 1, 2003, 1,269 cancers were detected in the screening arm and
      336 were detected in the control arm. A shift to more favorable clinical stages
      and histological grades on biopsy was seen in the screening arm of the trial. T1C
      and T2 cancers were 5.8 and 6.2 times more often diagnosed, respectively, in the
      screening arm than in the control arm of the trial. Only 4.6% of control arm
      cancers were found through opportunistic screening. CONCLUSIONS: Although a
      favorable shift in prognostic factors was seen for the screening arm of the
      trial, these results do not provide evidence that prostate cancer screening has
      an effect on prostate cancer mortality.

PMID- 15947596
TI  - Intermediate term biochemical progression rates after radical prostatectomy and
      radiotherapy in patients with screen detected prostate cancer.
AB  - PURPOSE: We compared biochemical progression rates measured by increasing
      prostate specific antigen (PSA) levels using a standard definition of biochemical
      recurrence among patients with screen detected prostate cancer treated with
      radical prostatectomy (RP) or radiotherapy (RT). MATERIALS AND METHODS: A total
      of 1,939 patients diagnosed with clinically localized prostate cancer in a
      community based screening study from 1989 to 1998, followed through 2001, were
      treated with RP or RT and agreed to enroll in a followup study. This prospective
      cohort study (median followup 62 months, range 0.2 to 141) used adjusted Cox
      proportional hazards models to examine time to progression. Selection bias was
      addressed with propensity scores. Biochemical evidence of cancer progression was
      defined as PSA greater than 0.2 ng/ml in patients who underwent RP and 3
      consecutive PSA increases as recommended by the American Society for Therapeutic
      Radiology and Oncology criteria for radiotherapy. RESULTS: Of the patients 17%
      had evidence of cancer progression. The percentage with progression-free survival
      at 5 and 9 years for RP was 84% and 76%, respectively, and for RT 80% and 70%,
      respectively. Cox proportional hazards models produced a hazard ratio of 1.63
      (95% CI, 1.12, 2.38) for RT compared with RP, adjusting for clinical stage,
      Gleason grade, preoperative PSA, biopsy age, treatment year and propensity for
      treatment type. CONCLUSIONS: With intermediate term followup, patients treated
      with RT were more likely to have cancer progression than with RP adjusting for
      demographics, clinical factors, selection bias and treatment year.

PMID- 15947597
TI  - Radical perineal prostatectomy for the treatment of localized prostate cancer in
      morbidly obese patients.
AB  - PURPOSE: We assessed the feasibility of radical perineal prostatectomy (RPP) in
      morbidly obese patients with clinically organ confined prostate cancer. MATERIALS
      AND METHODS: Of 1,265 consecutive patients who underwent RPP at our institution
      from 1992 to 2003 we identified 18 with a body mass index (BMI) of 40 kg/m or
      greater. Demographic and clinical patient characteristics were obtained from the
      medical records, which were further reviewed to identify the perioperative
      incidence of surgical and anesthesia related complications. RESULTS: Median BMI
      was 41.7 kg/m (range 40.2 to 62.6). Five patients had a BMI of 45.0 kg/m or
      greater. No intraoperative or anesthesia related complication occurred. Mean
      operative time +/- SD was 188 +/- 32 minutes and estimated blood loss was 573 +/-
      285 ml. None of the 18 patients received blood transfusions. During the immediate
      postoperative period 4 complications occurred in the form of lower extremity
      neuropraxia in 2 patients, local skin bleeding in 1 and early sepsis in 1
      requiring rehospitalization for intravenous antibiotics. Mean operative time and
      estimated blood loss were significantly lower when surgery was performed by a
      highly experienced surgeon compared with experienced surgeons (174 +/- 21 vs 235
      +/- 10 minutes and 485 +/- 258 vs 838 +/- 197 ml, p = 0.001 and 0.027,
      respectively). CONCLUSIONS: RPP in morbidly obese patients is feasible and it is
      associated with acceptable perioperative morbidity. The perineal approach should
      be considered in morbidly obese patients seeking surgical treatment for
      clinically localized prostate cancer.

PMID- 15947598
TI  - Classification and trends of perioperative morbidities following laparoscopic
      radical prostatectomy.
AB  - PURPOSE: We classified and assessed trends in the incidence, severity and
      management of perioperative morbidity following laparoscopic radical
      prostatectomy (LRP). MATERIALS AND METHODS: We retrospectively reviewed the
      records of 250 patients with clinically localized prostate cancer who underwent
      transperitoneal LRP, as performed by 2 surgeons (CPP and LMS), between April 2001
      and March 2004. The Clavien classification system was used to grade complications
      for cases completed laparoscopically. RESULTS: In the 246 cases completed
      laparoscopically 20 grade II, 12 grade III and 2 grade IV complications were
      noted during a mean followup of 13.7 months (overall complication rate 13.8%).
      Median hospital stay was 2 days (range 2 to 8) and median duration of bladder
      catheterization was 10 days (range 3 to 36). Postoperative ileus that prolonged
      hospital stay was the most frequent complication and it occurred in 8 patients
      (3.3%). Seven patients required blood transfusion (2.8%). Bladder neck
      contracture was observed in 3 patients (1.2%). A total of 11 complications
      occurred in the first 50 cases, while 12, 6, 8 and 1 occurred in cases 51 to 100,
      101 to 150, 151 to 200 and 201 to 250, respectively. CONCLUSIONS: Perioperative
      complications following LRP are mostly self-limited and grade II or III (94.1%).
      The incidence of complications and need for conversion to open radical
      prostatectomy decreased with experience. Uniform reporting and grading of
      surgical complications via a standardized classification system may permit more
      meaningful comparisons among different centers and surgical techniques.

PMID- 15947599
TI  - Effectiveness of cyproterone acetate in achieving castration and preventing
      luteinizing hormone releasing hormone analogue induced testosterone surge in
      patients with prostate cancer.
AB  - PURPOSE: To our knowledge this study represents the first analysis monitoring the
      efficacy of cyproterone acetate (CPA) monotherapy for achieving castrate
      testosterone levels prior to administering a luteinizing hormone-releasing
      analogue (LHRHA) for treating prostate cancer in the prostate specific antigen
      (PSA) era. MATERIALS AND METHODS: Patients with untreated locally advanced or
      metastatic prostate cancer were recruited prospectively. Treatment involved a 28
      day course of oral cyproterone acetate and LHRHA depot injection on day 14.
      Patients had serum PSA, luteinizing hormone and testosterone monitored at
      intervals during a 56-day period. RESULTS: A total of 15 patients with a mean age
      of 74 years completed the study. Near castrate serum testosterone was achieved on
      day 7 (mean +/- 95% CI 83.38 +/- 17.87 ng/dl). There was a significant
      testosterone increase after LHRHA administration on day 14 compared with the
      level of 160.23 +/- 36.60 ng/dl on day 16 (p <0.01). Serum luteinizing hormone
      mirrored testosterone, increasing from a mean of 4.93 +/- 0.61 to 15.4 +/- 6.12
      nmol/l after LHRHA administration (p <0.01). Mean serum PSA demonstrated a
      decrease from 199.25 +/- 6.12 microg/l at day 0 to 43.77 +/- 33.08 microg/l by
      day 56. There was no increase in serum PSA after LHRHA administration.
      CONCLUSIONS: Two weeks of priming with CPA does not eliminate the surge in serum
      testosterone (testosterone flare) upon LHRHA administration but the testosterone
      increase does not exceed pretreatment levels. Furthermore, 2 weeks of CPA may not
      offer a benefit over 1 week in lowering serum testosterone. Finally, there is no
      increase in serum PSA when LHRHA is administered after priming with CPA.

PMID- 15947600
TI  - Impact of the number of positive lymph nodes on disease-free survival in patients
      with pathological stage B1 nonseminomatous germ cell tumor.
AB  - PURPOSE: The prognostic significance of the number of metastatic lymph nodes
      detected at surgery on survival is well documented for breast and colon cancer,
      and it has recently been reported in bladder cancer. We tested this hypothesis in
      patients with pathological stage B1 nonseminomatous germ cell tumor (NSGCT).
      MATERIAL AND METHODS: This series included 118 patients with pathological stage
      B1 NSGCT (5 or fewer positive lymph nodes) at primary retroperitoneal lymph node
      dissection who did not receive adjuvant chemotherapy at a followup of greater
      than 24 months. RESULTS: Five-year disease-free survival (DFS) was 68% at a
      median followup of 43 months. Median followup in patients without recurrence was
      67.4 months and median time to recurrence was 5.0 months. The mean and median
      number of positive lymph nodes was 2.0. Five-year DFS for 1 or 2 and 3 to 5
      positive lymph nodes was 72% and 59%, respectively (p = 0.0847). Five-year DFS
      for lymph node density less or greater than 0.05 was 75% and 66%, respectively (p
      = 0.261). Neither the number of positive lymph nodes (continuous and categorical
      p = 0.201 and 0.271) or the ratio of the number of positive lymph nodes to the
      total number resected (continuous and categorical p = 0.415 and 0.998,
      respectively) predicted recurrence. CONCLUSIONS: Primary retroperitoneal lymph
      node dissection is curative in patients with pathological stage B1 NSGCT and DFS
      does not seem to be influenced by the number or the ratio of positive lymph nodes
      resected. This information may be helpful in limiting adjuvant chemotherapy in
      patients otherwise cured by surgery.

PMID- 15947607
TI  - Absence of bacterial and viral DNA in bladder biopsies from patients with
      interstitial cystitis/chronic pelvic pain syndrome.
AB  - PURPOSE: We examined bladder biopsies from women with interstitial
      cystitis/chronic pelvic pain syndrome (IC/CPPS) for the presence of bacterial and
      viral DNA sequences using polymerase chain reaction. MATERIALS AND METHODS:
      Bladder biopsies were taken during cystoscopy from patients under investigation
      for IC/CPPS, or controls undergoing colposuspension for stress incontinence.
      Biopsies were snap frozen to -70C. After DNA extraction, polymerase chain
      reaction (PCR) using specific primers for the hypoxanthine-guanine phosphoribosyl
      transferase gene confirmed the presence of human DNA. PCR for bacterial and viral
      gene sequences was performed using specific primers. Positive reactions were
      repeated to confirm the signal. RESULTS: A total of 92 patients with IC/CPPS (12
      who met the National Institute of Diabetes and Digestive and Kidney Diseases
      criteria and 80 who did not) and 91 controls were recruited. PCR for hypoxanthine
      guanine phosphoribosyl transferase gene was positive in all samples. PCR for the
      16S ribosomal RNA gene, as well as for adenovirus, cytomegalovirus, herpes
      simplex virus types I and II, human papillomavirus (all subtypes) and Chlamydia
      trachomatis were negative in all samples. CONCLUSIONS: IC/CPPS is not associated
      with persistence of viral and bacterial DNA in the bladder. A chronic infective
      etiology for the condition is excluded by these findings.

PMID- 15947608
TI  - Integration of myofascial trigger point release and paradoxical relaxation
      training treatment of chronic pelvic pain in men.
AB  - PURPOSE: A perspective on the neurobehavioral component of the etiology of
      chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS) is emerging. We
      evaluated a new approach to the treatment of CP/CPPS with the Stanford developed
      protocol using myofascial trigger point assessment and release therapy (MFRT) in
      conjunction with paradoxical relaxation therapy (PRT). MATERIALS AND METHODS: A
      total of 138 men with CP/CPPS refractory to traditional therapy were treated for
      at least 1 month with the MFRT/PRT protocol by a team comprising a urologist,
      physiotherapist and psychologist. Symptoms were assessed with a pelvic pain
      symptom survey (PPSS) and National Institutes of Health-CP Symptom Index. Patient
      reported perceptions of overall effects of therapy were documented on a global
      response assessment questionnaire. RESULTS: Global response assessments of
      moderately improved or markedly improved, considered clinical successes, were
      reported by 72% of patients. More than half of patients treated with the MFRT/PRT
      protocol had a 25% or greater decrease in pain and urinary symptom scores, as
      assessed by the PPSS. In those at the 50% or greater improvement level median
      scores decreased 69% and 80% for pain and urinary symptoms, respectively. The 2
      scores decreased significantly by a median of 8 points when the 25% or greater
      improvement was first observed, that is after a median of 5 therapy sessions.
      PPSS and National Institutes of Health-CP Symptom Index showed similar levels of
      improvement after MFRT/PRT protocol therapy. CONCLUSIONS: This case study
      analysis indicates that MFRT combined with PRT represents an effective
      therapeutic approach for the management of CP/CPPS, providing pain and urinary
      symptom relief superior to that of traditional therapy.

PMID- 15947609
TI  - Treatment of chronic bacterial prostatitis with levofloxacin and ciprofloxacin
      lowers serum prostate specific antigen.
AB  - PURPOSE: We compared baseline and post-therapy prostate specific antigen (PSA) in
      patients with chronic bacterial prostatitis who were treated with levofloxacin or
      ciprofloxacin. MATERIALS AND METHODS: Subset analysis was done using a
      randomized, multicenter, double-blind, active control trial of 500 mg
      levofloxacin daily for 28 days vs 500 mg ciprofloxacin twice daily in 28 days in
      men with chronic bacterial prostatitis. RESULTS: Of the 377 men in the intent to
      treat population, including 197 treated with levofloxacin and 180 treated with
      ciprofloxacin, 35 on levofloxacin and 37 on ciprofloxacin with baseline PSA
      greater than 4 ng/ml were included in this analysis. Excluded from analysis were
      2 levofloxacin treated patients with extremely high PSA at baseline (62 and 103
      ng/ml, respectively). Mean baseline PSA +/- SD in the patients analyzed was 8.33
      +/- 4.46 ng/ml, which decreased to 5.36 +/- 3.82 ng/ml after therapy. There was
      no significant difference in the mean change in PSA between the levofloxacin and
      ciprofloxacin groups. Approximately 42% of patients with increased baseline PSA
      had a post-therapy PSA of 4 ng/ml or less. Of patients who were microbiologically
      evaluable and had normalized PSA after therapy levofloxacin eradicated the
      pathogen in 90.9% (10 of 11). However, of patients in whom post-therapy PSA
      remained increased the microbiological eradication rate was 69.2% (9 of 13).
      Similarly 93.3% of the ciprofloxacin group (14 of 15 patients) with normalized
      post-therapy PSA experienced microbiological eradication compared with 61.5% (8
      of 13) with continued increased PSA after therapy. CONCLUSIONS: Approximately 20%
      of patients diagnosed with chronic bacterial prostatitis had increased PSA. A
      significant decrease in PSA was observed in these patients after treatment with
      levofloxacin or ciprofloxacin. An association was observed between bacterial
      persistence and the likelihood that PSA would return to normal.

PMID- 15947613
TI  - Randomized trial of the efficacy of tamsulosin, nifedipine and phloroglucinol in
      medical expulsive therapy for distal ureteral calculi.
AB  - PURPOSE: Recent studies show the interesting efficacy of different drug
      combinations for the spontaneous expulsion of distal ureteral stones. We
      performed a randomized, prospective study to assess and compare the efficacy of 3
      drugs as medical expulsive therapy for distal ureteral calculi. MATERIALS AND
      METHODS: A total of 210 symptomatic patients with distal ureteral calculi greater
      than 4 mm were randomly allocated to home treatment with phloroglucinol,
      tamsulosin or nifedipine (groups 1 to 3, respectively). Each group was given a
      corticosteroid drug and antibiotic prophylaxis with an injectable nonsteroidal
      anti-inflammatory drug was also used on demand. The primary end point was the
      expulsion rate and the secondary end points were expulsion time, analgesic use,
      need for hospitalization and endoscopic treatment as well as the number of
      workdays lost, quality of life and drug side effects RESULTS: The expulsion rate
      was significantly higher in group 2 (97.1%) than in groups 1 (64.3%, p <0.0001)
      or 3 (77.1%, p <0.0001). Group 2 significantly achieved stone passage in a
      shorter time than the other 2 groups and showed a significantly decreased number
      of hospitalizations as well as a better decrease in endoscopic procedures
      performed to remove the stone. The control of renal colic pain was significantly
      superior in group 2 compared with the other groups, resulting in fewer workdays
      lost. Group 3 showed lower analgesic use and decreased workdays lost compared
      with group 1. No difference in side effects was observed among the groups.
      CONCLUSIONS: Medical expulsive therapy should be considered for distal
      ureterolithiasis without complications before ureteroscopy or extracorporeal
      lithotripsy. The use of tamsulosin in this treatment regimen produced stone
      expulsion in almost all cases in a short time, allowing complete home patient
      treatment.

PMID- 15947618
TI  - Impact of food intake on urodynamic features of orthotopic urinary reservoirs.
AB  - PURPOSE: The inconsistency of urodynamic characteristics among patients with
      similar, well detubularized urinary reservoirs together with the persistence of
      nocturnal incontinence in almost a third of such patients has motivated many
      groups to study in depth the inherent physiological characters of the intestinal
      segments used. One of the most critical criteria is the effect of food intake on
      such isolated segments. We determined the effect of food intake on the urodynamic
      behavior of urinary intestinal reservoirs. MATERIALS AND METHODS: A total of 50
      male patients with well detubularized orthotopic reservoirs (hemiKock or W
      neobladders) after radical cystectomy underwent medium fill enterocystometry
      while fasting for 8 hours. Patients were then given a standardized caloric diet
      and the test was repeated 2 hours after food intake. Comparisons were made in the
      whole group of patients and subsets according to continence status, reservoir
      configuration and reservoir duration. RESULTS: The only significant and
      consistent finding was the decrease in maximum enterocystometric capacity. This
      decrease was statistically significant when calculated for the fasting and
      postprandial states in the whole group (mean +/- SD 539.1 +/- 155.7 and 495.9 +/-
      146.2 ml), in continent patients (538 +/- 177 and 505 +/- 168.5 ml) and in
      patients with enuresis (539 +/- 177 and 481 +/- 106.8 ml, respectively). While
      the frequency and amplitude of phasic contractions were notably increased
      postprandially, baseline pressure at mid and maximum capacity were observed to be
      lowered. However, neither effect achieved statistical significance. CONCLUSIONS:
      Definite urodynamic changes occur in intestinal urinary reservoirs in response to
      food intake, denoting that these detubularized intestinal segments retain at
      least in part their native behavior in response to eating. The consistent
      decrease in maximum capacity together with increased phasic motor activity in a
      subset of these patients may explain their incontinence episodes. Changing food
      composition and habits may improve the continence state in this subset of
      patients.

PMID- 15947623
TI  - A comparison of urodynamic diagnoses and detrusor muscle function in white and
      South Indian Asian women.
AB  - PURPOSE: We compared urodynamic data and the final diagnosis after testing
      between white and Asian women investigated for urinary incontinence. MATERIALS
      AND METHODS: Urodynamic traces of consecutive women investigated between January
      2002 and December 2003 were reviewed. Urodynamic diagnoses were classified as
      normal, urodynamic stress incontinence, detrusor overactivity (DOA) or mixed
      incontinence. In DOA cases the amplitude and number of detrusor contractions, and
      the volume at which the first involuntary contraction occurred were recorded.
      Data were compared by ethnic group. RESULTS: The distribution of diagnoses was
      significantly different between Asian and white women (p <0.0001). In Asian and
      white women we noted urodynamic stress incontinence in 22% and 53% (OR 0.24, 95%
      CI 0.13 to 0.48), DOA in 28% and 17% (OR 1.88, 95% CI 0.98 to 3.60) and mixed
      incontinence in 22% and 7% (OR 3.74, 95% CI 1.70 to 8.22), respectively. Post
      void residual volume (p = 0.02), volume at strong desire to void (p = 0.03) and
      cystometric capacity (p = 0.0002) were lower in Asian women. In those with DOA
      the first contraction occurred at a lower volume in Asian woman (57 vs 179 ml, p
      = 0.002). Asian women had more contractions (5 vs 3, p = 0.009) with higher
      maximum (50 vs 32 cm H2O, p = 0.004) and average (34.4 vs 25.3 cm H2O, p = 0.03)
      detrusor pressure. CONCLUSIONS: In women who undergo urodynamics a greater
      proportion of Asian women have DOA and mixed incontinence compared with white
      women. Functional differences in detrusor contraction pressures exist, which may
      suggest a fundamental difference in bladder function or disease etiology.
      Exploration of this theory requires further study.

PMID- 15947624
TI  - The effect of fluid intake on urinary symptoms in women.
AB  - PURPOSE: We determined the effect of caffeine restriction and fluid manipulation
      in the treatment of patients with urodynamic stress incontinence and detrusor
      overactivity. MATERIALS AND METHODS: This was a 4-week randomized, prospective,
      observational crossover study in 110 women with urodynamic stress incontinence
      (USI) or idiopathic detrusor overactivity (IDO) to determine the effect of
      caffeine restriction, and of increasing and decreasing fluid intake on urinary
      symptoms. Data were recorded in a urinary diary for the entire study period on
      urgency episodes, frequency, pad weight increase, wetting episodes and quality of
      life. RESULTS: A total of 69 women with a mean age of 54.8 years completed the
      study, including 39 with USI and 30 with IDO. In the IDO group decreasing fluid
      intake significantly decreased voiding frequency, urgency and wetting episodes
      with improved quality of life. In the USI group there was a significant decrease
      in wetting episodes when fluid intake was decreased. Changing from caffeine
      containing to decaffeinated drinks produced no improvement in symptoms.
      CONCLUSIONS: Conservative and life-style interventions are first line treatments
      in the management of incontinence and storage lower urinary tract symptoms. This
      study shows that a decrease in fluid intake improves some of these symptoms in
      patients with USI and IDO and, therefore, it should be considered when treating
      such patients.

PMID- 15947625
TI  - Weight loss: a novel and effective treatment for urinary incontinence.
AB  - PURPOSE: We evaluated the effect of weight loss on urinary incontinence (UI) in
      overweight and obese women. MATERIALS AND METHODS: A randomized, controlled
      clinical trial was conducted among overweight and obese women experiencing at
      least 4 UI episodes per week. Women were randomly assigned to a 3-month liquid
      diet weight reduction program (24 in the immediate intervention group) or a wait
      list delayed intervention group (24 in the wait-list control group). Participants
      in the wait-list control group began the weight reduction program in month 3 of
      the study. All women were followed for 6 months after completing the weight
      reduction program. Wilcoxon tests were used to compare intergroup differences in
      change in weekly UI episodes and quality of life scores. RESULTS: A total of 48
      women were randomized and 40 were assessed 3 months after randomization. Median
      (with 25% to 75% interquartile range [IQR]) baseline age was 52 years (IQR 47 to
      59), weight was 97 kg (IQR 87 to 106) and UI episodes were 21 weekly (IQR 11 to
      33). Women in the immediate intervention group had a 16 kg (IQR 9 to 20) weight
      reduction compared with 0 kg (IQR -2 to 2) in the wait-list control group (p
      <0.0001). The immediate intervention group experienced a 60% reduction (IQR 30%
      to 89%) in weekly UI episodes compared with 15% (IQR -9% to 25%) in the wait-list
      control group (p <0.0005) and had greater improvement in quality of life scores.
      Stress (p =0.003) and urge (p =0.03) incontinent episodes decreased in the
      immediate intervention vs wait-list control group. Following the weight reduction
      program the wait-list control group experienced a similar median reduction in
      weekly UI episodes (71%). Among all 40 women mean weekly UI episodes decreased
      54% (95% CI 40% to 69%) after weight reduction and the improvement was maintained
      for 6 months. CONCLUSIONS: Weight reduction is an effective treatment for
      overweight and obese women with UI. Weight loss of 5% to 10% has an efficacy
      similar to that of other nonsurgical treatments and should be considered a first
      line therapy for incontinence.

PMID- 15947626
TI  - Botulinum toxin type a is a safe and effective treatment for neurogenic urinary
      incontinence: results of a single treatment, randomized, placebo controlled 6
      month study.
AB  - PURPOSE: We determined the safety and efficacy of each of 2 doses of botulinum
      toxin type A (BTX-A) (200 or 300 U BOTOX) injected into the detrusor for urinary
      incontinence caused by neurogenic detrusor overactivity of predominantly spinal
      cord origin. MATERIALS AND METHODS: A total of 59 patients with urinary
      incontinence caused by neurogenic detrusor overactivity (due to spinal cord
      injury in 53 and multiple sclerosis in 6) requiring clean intermittent self
      catheterization were randomized to receive a single dose into the detrusor of BTX
      A (200 U or 300 U) or placebo. Changes in daily frequency of urinary incontinence
      episodes were monitored via a patient bladder diary during 24 weeks. Key
      urodynamic assessments (maximum cystometric capacity, reflex detrusor volume and
      maximum detrusor pressure during bladder contraction) were used to provide
      objective measures of the treatment effect on bladder function. The impact of
      treatment on quality of life was assessed using the Incontinence Quality of Life
      questionnaire. RESULTS: There were significant posttreatment decreases in
      incontinence episodes from baseline in the 2 BTX-A groups (p </=0.05) but not in
      the placebo group. In addition, more patients who received BTX-A reported no
      incontinence episodes during at least 1 posttreatment evaluation period. Positive
      treatment effects were also reflected by significant improvements in bladder
      function in the BTX-A groups, as assessed by urodynamics and in patient quality
      of life. Benefits were observed from the first evaluation at week 2 to the end of
      the 24-week study. No safety concerns were raised. CONCLUSIONS: Intramuscular
      injections of BTX-A into the detrusor can provide rapid, well tolerated,
      clinically significant decreases in the signs and symptoms of urinary
      incontinence caused by neurogenic detrusor overactivity during a 24-week study
      period.

PMID- 15947627
TI  - Changes in overactive bladder symptoms after discontinuation of successful 3
      month treatment with an antimuscarinic agent: a prospective trial.
AB  - PURPOSE: We measured changes in overactive bladder (OAB) symptoms after the
      discontinuation of successful 3-month treatment with an antimuscarinic agent and
      the pretreatment factors that contributed to re-treatment. MATERIALS AND METHODS:
      A total of 68 women who reported improvement in OAB symptoms after 4 weeks of
      treatment with 20 mg propiverine hydrochloride daily were prospectively enrolled
      in a protocol consisting of 8 more weeks of medication and a 4-week
      discontinuation period. Frequency-volume charts were assessed before treatment,
      after 12 weeks of therapy and 4 weeks after discontinuation along with a
      questionnaire assessing satisfaction with treatment and desire for further
      treatment. The Indevus Urgency Severity Score was used to quantify the degree of
      urgency and changes during treatment. Changes in frequency, nocturia, and urgency
      score at 12 and 16 weeks were evaluated. Pretreatment factors leading to re
      treatment were determined, including patient characteristics, voiding symptom
      parameters and urodynamic indexes. RESULTS: OAB symptoms at 16 weeks (4 weeks
      after the cessation of antimuscarinic medication) were improved compared with
      baseline but worse than after 12 weeks. At baseline, and 12 and 16 weeks mean
      daily frequency was 11.2, 7.3 and 8.3, mean nocturia frequency was 1.6, 0.4 and
      0.8, and the urgency score was 1.7, 0.6 and 1.2, respectively. The re-treatment
      rate was 35.3%. Patients in the re-treatment group were significantly older (58.8
      vs 47.3 years, p <0.001) and had higher initial urgency scores (1.9 vs 1.6, p =
      0.034) than those requiring no further treatment. Of 23 patients who underwent a
      urodynamic study those without detrusor overactivity (DO) maintained significant
      improvement regarding frequency after cessation of medication, whereas those with
      DO did not, although their frequency was improved compared with baseline (p =
      0.02). The re-treatment rate was higher in patients with DO but the difference
      was not statistically significant (60.9% vs 39.1%, p = 0.45). CONCLUSIONS: Of
      patients 35% sought re-treatment 1 month after the discontinuation of
      antimuscarinic therapy. Patients older than 55 years or those with severe urgency
      may more frequently receive re-treatment and patients with DO may experience more
      rapid symptom recurrence after medication discontinuation.

PMID- 15947628
TI  - Effect of lower urinary tract symptoms on the incidence of erectile dysfunction.
AB  - PURPOSE: We determined the effect of lower urinary tract symptoms (LUTS) on the
      incidence of erectile dysfunction (ED). MATERIALS AND METHODS: The target
      population consisted of all men 50, 60 or 70 years old residing in Tampere area,
      Finland in 1994. Questionnaires were mailed to 3,143 men in 1994 and to 2,864 men
      5 years later. The followup sample consisted of the 1,683 men who responded to
      baseline and followup questionnaires. We estimated the effect of LUTS and bother
      on the incidence of ED during the 5-year followup among the 1,126 men free from
      ED at baseline. ED was assessed by 2 questions on subject ability to achieve and
      maintain erection sufficient for intercourse and LUTS assessed by the Danish
      Prostatic Symptom Score. Logistic regression model was used in the multivariate
      analysis. RESULTS: The incidence of ED increased with the presence and with the
      intensity of urinary symptoms and bother at baseline. Compared with men with LUTS
      score 0, the incidence of ED was 2.7 (95% CI 1.3-5.5) times higher among men with
      score 7 to 11, and 3.1 times with score 12 or more. The incidence of ED increased
      by 5% for each 1-point increment in LUTS score, while it increased by 12% and 11%
      for 1-point increment in cumulative symptom or bother score, respectively. Men
      with cumulative symptoms or bother score 4 or more were significantly 2.0 to 2.7
      times at higher incidence of ED relative to those who were free from symptoms or
      bother at baseline. Only overflow incontinence (OR = 2.2) and incomplete emptying
      (OR = 1.8) independently increased the incidence of ED. CONCLUSIONS: Lower
      urinary tract symptoms and bother independently increase the incidence of
      erectile dysfunction.

PMID- 15947629
TI  - Holmium laser bladder neck incision versus holmium enucleation of the prostate as
      outpatient procedures for prostates less than 40 grams: a randomized trial.
AB  - PURPOSE: Bladder neck incision (BNI) is a common, minimally invasive treatment
      option for bladder outflow obstruction in men with a small prostate. We compared
      BNI using the holmium:YAG laser to holmium enucleation of the prostate (HoLEP) in
      a prospective, randomized, urodynamically based trial. MATERIALS AND METHODS: A
      total of 40 patients with urodynamic obstruction (Schafer grade 2 or greater) and
      a prostate of 40 gm or greater on transrectal ultrasound (TRUS) were randomized
      equally to holmium laser BNI (HoBNI) or HoLEP as an outpatient procedure. The
      outcomes assessed were operative time, catheter time and hospital time. American
      Urological Association and quality of life scores, and maximal urinary flow rates
      were measured at baseline, and 1, 3, 6 and 12 months postoperatively, while
      pressure flow studies and TRUS volume measurement were performed at baseline and
      6 months. RESULTS: The 2 groups were well matched for all variables at baseline.
      HoBNI was significantly more rapid to perform than HoLEP (p <0.001). Two patients
      (10%) in the HoBNI group required recatheterization compared with none in the
      HoLEP group. There was no significant difference in catheter time (22.9 vs 23.2
      hours) or hospital time (12.3 vs 13.7 hours) between the groups. Five patients
      remained obstructed urodynamically at 6 months. All were in the HoBNI group and 4
      of the 5 men had a prostate that was greater than 30 gm. Four of these patients
      required HoLEP for persistent lower urinary tract symptoms. In the remaining
      unoperated patients there were no significant differences in American Urological
      Association and quality of life scores or in the maximal urinary flow rate at
      each assessment. At 6 months detrusor pressure at maximal urinary flow was
      significantly lower (p <0.05) and TRUS volume was significantly smaller (p
      <0.001) in the HoLEP group There was significantly more early stress incontinence
      postoperatively in the HoLEP group but no bladder neck contractures were
      detected. CONCLUSIONS: Relief of obstruction was better after HoLEP and fewer
      patients required recatheterization or reoperation, although more reported early
      postoperative stress incontinence. Catheter time, hospital time and perioperative
      morbidity were similar. HoBNI and HoLEP are safe and feasible as outpatient
      procedures in patients with a small prostate but HoBNI is more rapid to perform.

PMID- 15947642
TI  - Living unrelated donor renal transplantation: a single center experience.
AB  - PURPOSE: Living, genetically unrelated donor renal transplantation (LURT) is
      being performed with increasing frequency. We evaluated our single center
      experience with LURT and compared this to a cohort of living related donor renal
      transplants (LRT) to evaluate the short-term success of LURT at our center.
      MATERIALS AND METHODS: We identified 99 consecutive patients who underwent LURT
      at our center and had at least 1 year of followup data. A control cohort of 99
      patients who underwent LRT at our center matched for age, number of transplants
      and date of transplant was also identified. One-year graft and patient survival,
      and serum creatinine levels at 1, 3, 6 and 12 months were compared between the
      groups. Our data were compared with national and international data. RESULTS: At
      our center 1-year graft survival was 95% in the LURT and LRT cohorts. One-year
      LURT patient survival was 99% compared with 97% in the LRT group and the serum
      creatinine levels were not significantly different. CONCLUSIONS: Patients
      undergoing LURT at our center have excellent 1-year graft and patient survival
      compared with LRT performed at our center, and national and international LURT.
      Genetically unrelated kidney donors should continue to be used to expand the
      kidney donor pool.

PMID- 15947643
TI  - Impact of intraoperative heparin on laparoscopic donor nephrectomy.
AB  - PURPOSE: At many centers systemic heparinization is performed during laparoscopic
      donor nephrectomy because of concerns regarding graft thrombosis. However, no
      consensus exists in this regard. We evaluated the impact of intraoperative
      heparin on donor and recipient outcomes. MATERIALS AND METHODS: Between September
      2000 and February 2003, 79 consecutive patients underwent laparoscopic live donor
      left nephrectomy at our institution. They were sequentially divided into 2
      groups, that is group 1-the initial 40 patients who intraoperatively received
      5,000 IU heparin intravenously and group 2-subsequent patients who did not
      receive heparin. The 2 groups were well matched demographically. Data were
      compared using the paired 2-tailed t test. RESULTS: The 2 donor groups were
      comparable in regard to mean blood loss (139 vs 179 cc, p = 0.59), intraoperative
      urine output (1.6 vs 1.6 l, p = 0.74), warm ischemia time (4 vs 4.2 minutes, p =
      0.52), operative time (3.5 vs 3.5 hours, p = 0.97), and cold ischemia time (75 vs
      82 minutes, p = 0.38). Complications occurred in 1 patient in group 1
      (rhabdomyolysis induced acute renal failure) and in 2 in group 2 (chylous ascites
      and lumbar vein injury, respectively). No graft was lost due to vascular
      thrombosis in either group. Recipient immediate, early and delayed (6-month)
      graft function was comparable between the 2 groups. Acute rejection occurred in 5
      recipients in group 1 and 1 in group 2. There was 1 recipient death per group at
      delayed followup. CONCLUSIONS: Routine use of heparin during laparoscopic donor
      nephrectomy is not necessary. Because of its potential for causing intraoperative
      or early postoperative hemorrhage, we no longer routinely administer
      intraoperative heparin during laparoscopic donor nephrectomy at our institution.

PMID- 15947645
TI  - Chapter 1: The management of erectile dysfunction: an AUA update.

PMID- 15947646
TI  - The impact of age, body mass index and testosterone on erectile dysfunction.
AB  - PURPOSE: Erectile dysfunction (ED) may be associated with low serum total
      testosterone (T), low serum bioavailable testosterone (BAT) and high body mass
      index (BMI) in aging men. MATERIALS AND METHODS: A total of 675 workers (age
      range 45 to 60 years old) were entered into this study. Investigations were
      performed directly at their place of work. Exclusion criteria were abnormal
      urogenital status, antihypertensive drugs, medication possibly affecting the
      endocrine function and a history of previous pelvic trauma. T and sex hormone
      binding globulin were measured with commercially available assays, and BAT was
      calculated from T and sex hormone-binding globulin. BMI was assessed and every
      individual completed a self-administrated questionnaire for erectile function
      (International Index of Erectile Function [IIEF-5]). RESULTS: T and BAT showed a
      significantly negative correlation with age and BMI. Each additional year of
      increase in age caused a decrease in the IIEF-5 score of 0.195 (p <0.001).
      Increase in BMI by 1 kg/m reduced IIEF-5 by 0.141, independent of age (p =0.005).
      Multiple logistic regression analyses confirmed the influence of increased age
      and higher BMI on the risk of ED. The corresponding odds ratio for ED was 1.082
      (p <0.001) and 1.076 (p <0.001), respectively. These data indicate an increase in
      ED risk by 8.2% per year and by 7.6% per kg/m BMI. Severe cases of ED (IIEF-5
      score 7 or less) were significantly associated with a decrease in T and BAT.
      Individuals with low BAT (1 ng/ml or less) had a 3 times higher risk of severe ED
      compared with men with BAT greater than 1 ng/ml (odds ratio 3.045, 95% CI 1.088
      to 8.522, p =0.034). The result of the multiple logistic regression analysis was
      adjusted to age and BMI, and did not show a significant influence on the
      incidence of severe ED. CONCLUSIONS: BMI contributes strongly to ED. Low T or BAT
      are only relevant if IIEF-5 questionnaire results in severe ED.

PMID- 15947647
TI  - Are men with erectile dysfunction more likely to have hypertension than men
      without erectile dysfunction? A naturalistic national cohort study.
AB  - PURPOSE: : We examined whether men with erectile dysfunction (ED) are more likely
      to have hypertension than men without ED in a managed care setting. MATERIALS AND
      METHODS: : We used a naturalistic cohort design to compare hypertension
      prevalence rates in 285,436 men with ED to that in 1,584,230 men without ED from
      1995 through 2001. We also used a logistic regression model to isolate the effect
      of ED on the likelihood of hypertension after controlling for subject age, census
      regions and 9 concurrent diseases. The ED and the nonED cohort came from a
      nationally representative, managed care claims database that covers 51 health
      plans and 28 million members in the United States. Finally, the prevalence rate
      difference between members with and without ED, and the OR of having hypertension
      were calculated. RESULTS: : The hypertension prevalence rate was 41.2% in men
      with ED and 19.2% in men without ED. After controlling for subject age, census
      region and 9 concurrent diseases the OR was 1.383 (p <0.0001), which implies that
      the odds for men with ED to have hypertension were 38.3% higher than the odds for
      men without ED. CONCLUSIONS: : Men with ED were more likely to have hypertension
      than men without ED. This evidence supports the hypothesis that ED shares common
      risk factors with hypertension. It also suggests that men with ED and clinicians
      could use ED as an alerting signal to detect and treat undiagnosed hypertension
      earlier.

PMID- 15947648
TI  - Erectile dysfunction prevalence and sexual function status in patients with
      chronic obstructive pulmonary disease.
AB  - PURPOSE: We determined sexual status and erectile dysfunction (ED) in outpatients
      with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Between
      October 2002 and June 2003 a total of 60 successive outpatients with COPD
      enrolled in the study with written informed consent. Patients completed
      International Index of Erectile Function (IIEF) and Duke Activity Status Index
      questionnaires. They also underwent physical examination including urogenital
      examination and pulmonary assessment with spirometry, 6-minute walk test and
      arterial blood sample. COPD severity was determined according to Global
      Initiative for Chronic Obstructive Lung Disease criteria. RESULTS: After
      exclusion criteria 53 patients were assessed for statistical analysis. Mean
      patient age was 63.4 +/- 7.3 years. COPD severity in these patients was mild in
      13.2%, moderate in 34%, severe in 49.1% and very severe in 3.8%. Nearly half of
      the patients (49%) had no comorbid disease for ED and the most common comorbid
      disease was hypertension (34%). According to the erectile function domain of IIEF
      75.5% of patients were found to have ED with varying degrees (severe 28.3%,
      moderate 11.3%, mild to moderate 15.1% and mild 20.8%). Mean scores of all IIEF
      domains except sexual desire decreased with the increasing disease severity. A
      correlation was determined between severity and physical restrictions of COPD,
      and ED severity. CONCLUSIONS: The limitation of physical activity due to COPD
      also diminishes the sexual function of patients. This point must be kept in mind
      in the evaluation of patients with COPD.

PMID- 15947649
TI  - A survey of patients with inflatable penile prostheses for satisfaction.
AB  - PURPOSE: We assessed patient satisfaction with 3 types of penile prostheses,
      namely the AMS 700 Series(R), Mentor Alpha 1(R) and Mentor Alpha NB(R). MATERIALS
      AND METHODS: The subjects consisted of 330 patients selected by stratified,
      systematic random sampling from among 1,298 subjects undergoing virgin 3-piece
      inflatable penile implant surgeries performed by the same surgical team at 1
      hospital between January 1992 and December 1998. Data were collected by computer
      assisted telephone interviewing with a survey developed by the authors. The
      survey consisted of 37 questions in 7 sections, including 1 demographic section
      and 6 patient satisfaction sections. RESULTS: Of the 330 patients selected 248
      (75%) could be contacted. Of these, 199 (80%) responded to the full survey and
      the remaining 49 (20%) agreed to respond only to the question, "How satisfied are
      you with the prosthesis?" Of the 199 full responders 12 (6%) had AMS implants and
      187 (94%) had Mentor implants. Of the 49 single question responders 5 (10%) had
      AMS implants and 44 (90%) had Mentor implants. Of the 248 patients the overall
      satisfaction rate was 69%. Although there was no significant difference at the 5%
      level in patient satisfaction by implant type, responses tended to favor the
      Alpha IPPs in terms of overall sexual satisfaction (p =0.058), natural feeling of
      the prosthesis (p =0.061), flaccid appearance of the penis when deflated (p
      =0.054), and education with demonstration of inflation and deflation (p =0.075).
      CONCLUSIONS: There was a high degree of overall patient satisfaction across
      implant types.

PMID- 15947650
TI  - The efficacy of sildenafil citrate following radiation therapy for prostate
      cancer: temporal considerations.
AB  - PURPOSE: Erectile dysfunction is a recognized complication of radiation therapy
      for prostate cancer. Sildenafil citrate is a well-known management strategy for
      erectile dysfunction that has been found to be efficacious across a wide spectrum
      of comorbidities, including post-radiation erectile dysfunction. We defined the
      efficacy of sildenafil citrate in patients with erectile dysfunction following
      radiation therapy for prostate cancer and assessed the impact of the interval
      after radiation on the success of this therapy. MATERIALS AND METHODS: Baseline
      and followup data on 110 patients presenting with erectile dysfunction secondary
      to radiation for prostate cancer was obtained. A total of 68 patients underwent 3
      dimensional conformal external beam irradiation (CRT), while 42 underwent
      brachytherapy (BT) without androgen deprivation. All patients were considered to
      have erectile dysfunction after radiotherapy, as assessed by the International
      Index of Erectile Function (IIEF), and they were prescribed sildenafil citrate.
      Mean time +/- SD between the completion of radiation therapy and the initiation
      of sildenafil was 8 +/- 4 months. The response to sildenafil was assessed using
      the IIEF questionnaire. Within and between group comparisons were done for 3 time
      points, that is less than 12, 13 to 24 and 25 to 36 months following the
      completion of radiation therapy. RESULTS: The respective response rates in men
      who underwent BT/CRT at the 3 time points of less than 12, 13 to 24 and 25 to 36
      months was 76%/68%, 54%/46% and 44%/38%, respectively. Mean IIEF erectile
      function domain scores for these 3 time points after BT/CRT was 26/23, 22/19 and
      17/15, respectively. The percent of patients who achieved normalization of the
      IIEF erectile function domain at the 3 time points in the BT/CRT groups was
      60%/50%, 48%/42% and 26%/19%, respectively. CONCLUSIONS: Sildenafil citrate
      improves erectile function in men in whom erectile dysfunction develops following
      radiation therapy for prostate cancer. There is a clear time dependence for the
      response to this therapy with a stepwise decrease in all end points examined
      serially in a 3-year period.

PMID- 15947662
TI  - Robotic radical prostatectomy in the community setting--the learning curve and
      beyond: initial 200 cases.
AB  - PURPOSE: The introduction of robotic assistance has the potential to improve
      surgical outcomes and reduce the steep learning curve associated with
      conventional laparoscopic radical prostatectomy. We report on our experience with
      robotic radical prostatectomy in the community setting. MATERIALS AND METHODS: A
      total of 200 patients underwent robotic radical prostatectomy during 18 months.
      Prospective data collection included a quality of life (Expanded Prostate Cancer
      Index Composite) questionnaire, basic demographics, prostate specific antigen
      (PSA), clinical stage and Gleason grade. Operative outcome measures included
      operative time, estimated blood loss and complications. Postoperative outcome
      measures included hospital stay, catheter time, pathology, PSA and return of
      continence. RESULTS: Average operative time was 141 minutes with an estimated
      blood loss of 75 cc. The intraoperative complication rate was 1% with no
      mortality, reexploration or transfusion. Of the patients 95% were discharged home
      on postoperative day 1 (1 to 3) with hematocrit averaging 34.5 (range 25 to 45).
      The average difference in preoperative and postoperative hematocrit was 3 points
      (range -2 to 15). Average catheter time was 7.2 days (range 5 to 15). The
      positive margin rate was 10.5% for the entire series, 5.7% for T2 tumors, 28.5%
      (T3a), 20% (T3b) and 33% (T4a). Of the patients 95% had undetectable PSA (less
      than 0.1 ng/ml) at average followup of 9.7 months. Continence at 1, 3, 6, 9 and
      12 months was 47%, 78%, 89%, 92% and 98%, respectively. CONCLUSIONS: Our initial
      experience with robotic radical prostatectomy is promising. The learning curve
      was approximately 20 to 25 cases. With a structured methodical approach we were
      able to implement robotics safely and effectively into our community practice
      with minimal patient morbidity, and good oncological and functional outcomes.

PMID- 15947666
TI  - Ureteroscopy is safe and effective in prepubertal children.
AB  - PURPOSE: We present our experience performing ureteroscopy in prepubertal
      children. MATERIALS AND METHODS: We performed a retrospective cohort study of
      children 12 years or younger who underwent ureteroscopy at 2 institutions between
      1993 and 2003. Patient demographics, indications for surgery, operative
      technique, surgical outcomes and complications were recorded. RESULTS: A total of
      39 boys and 32 girls underwent 34 flexible and 47 rigid ureteroscopies.
      Retrograde access was obtained in 77 procedures, while 4 were performed via an
      antegrade approach. Mean age was 7.5 years (range 1 to 12) and mean followup was
      2.2 years (0.5 to 10). Endoscopic lithotripsy was performed in 65 cases, with a
      success rate of 98%. A ureteral stent was placed postoperatively in 55 patients.
      Endoscopic incision was performed for a ureteral stricture in 3 patients and for
      ureteropelvic junction obstruction in 6. An obstructing fibroepithelial polyp was
      found in 2 patients, 1 underwent removal of a foreign body and 4 did not have
      intraluminal pathology. Dilation of the ureteral orifice was required in 23 cases
      (30%). There were no intraoperative ureteral injuries. One patient had
      development of a ureteral stricture (complication rate 1.3%) that was
      successfully treated endoscopically. CONCLUSIONS: Rigid and flexible ureteroscopy
      can be performed safely and effectively in prepubertal children. Successful
      outcomes can be obtained for calculi that are similar to those in the adult
      population. Ureteroscopic treatment can be effective in selected children with
      intraluminal obstruction. To our knowledge this is the largest series in the
      literature to document outcomes of ureteroscopy in this age group.

PMID- 15947667
TI  - Laparoscopic assisted modification of the firlit abdominal wall plication.
AB  - PURPOSE: We describe a modification of the Firlit abdominal wall plication
      procedure for abdominal wall reconstruction in the prune-belly syndrome.
      MATERIALS AND METHODS: Five boys with the prune-belly syndrome and 1 with
      congenital atrophy or hypotrophy of the internal and external oblique muscles
      underwent laparoscopic assisted abdominal wall reconstruction. RESULTS: All 6
      patients had excellent cosmetic results, with no weakness or sagging of the
      abdominal wall. CONCLUSIONS: Laparoscopy appears to add to the Firlit procedure
      an increased measure of safety and a possible decrease in morbidity associated
      with opening the abdomen, and improved precision that enhances the results
      achieved with the original procedure and other abdominal wall repairs.

PMID- 15947668
TI  - Passerini-glazel feminizing genitoplasty: a long-term followup study.
AB  - PURPOSE: We report our experience with early 1-stage Passerini-Glazel feminizing
      genitoplasty with special emphasis on long-term results of vaginoplasty.
      MATERIALS AND METHODS: A total of 66 patients with ambiguous genitalia underwent
      1-stage Passerini-Glazel feminizing genitoplasty. Long-term followup included an
      outpatient visit at 1 year postoperatively and a genital assessment with the
      patient under general anesthesia performed before menarche courses in those
      operated on at age 6 months to 8 years, and at 2 years postoperatively for those
      operated on at 9 years or older. RESULTS: All patients underwent the first long
      term followup evaluation and no major complications were observed. The second
      long-term followup evaluation was performed in 46 patients (70%). In all cases
      the vaginal introitus was located in the physiological position and was large and
      elastic. Vaginal caliber at the suture line between the tubularized flap and
      vaginal mucosa was the same size as the vaginal introitus and distal native
      vagina in 20 of 46 patients (43%), slightly smaller in 10 (22%) and stenotic in
      16 (35%). Stenosis at the suture line was corrected with simple Y-V
      introitoplasty performed at the same followup visit. CONCLUSIONS: Early 1-stage
      Passerini-Glazel feminizing genitoplasty is a safe and effective procedure that
      allows total surgical correction of ambiguous genitalia in infancy and good
      cosmetic results. Incidence of vaginal stenosis at the suture line is high but it
      can be repaired with simple introitoplasty performed before menarche occurs. Good
      functional results are presumed.

PMID- 15947669
TI  - Voiding pattern and acquisition of bladder control from birth to age 6 years--a
      longitudinal study.
AB  - PURPOSE: We describe the voiding pattern and acquisition of bladder control in
      healthy children up to age 6 years. MATERIALS AND METHODS: We determined age for
      daytime and nighttime dryness, voiding patterns, voiding volumes and post-void
      residual volume per 4 hours individually and noninvasively every 3 months up to
      age 3 years and every 6 months up to age 6 years in 36 female and 23 male
      patients using 4-hour voiding observation and uroflowmetry/ultrasound. RESULTS:
      Median age for attaining daytime and nighttime dryness was 3.5 and 4 years,
      respectively. No significant difference was found between girls and boys. All but
      1 child attained daytime dryness an average of 10 months before attaining
      nighttime dryness. Bladder sensation was reported in 31%, 79% and 100% of
      patients at ages 2, 3 and 4 years, respectively. Median bladder capacity was 67
      ml, 123 ml and 140 ml at years 1, 3 and 6, respectively. Median post-void
      residual volume was 5.5 ml, 0 ml and 2 ml at ages 1, 3 and 6 years, respectively.
      CONCLUSIONS: Today bladder control is acquired at a later stage despite earlier
      awareness of bladder function. The occurrence of bladder sensation from age 1.5
      years motivates an earlier start with toilet training. Infants with small post
      void residual volume at age 6 months or large bladder capacity will probably
      attain daytime dryness earlier than those with large post-void residual volume at
      age 6 months or small bladder capacity.

PMID- 15947670
TI  - Desmopressin associated symptomatic hyponatremic hypervolemia in children. Are
      there predictive factors?
AB  - PURPOSE: Desmopressin is widely used in primary nocturnal enuresis, bleeding
      disorders, central diabetes insipidus and diagnostic urine concentration testing.
      Hyponatremic hypervolemia leading to seizures has been reported as a rare but
      potentially life threatening side effect of desmopressin therapy. We sought to
      identify factors that predispose patients to hyponatremia and to find predictive
      factors associated with increased risk of water intoxication. MATERIALS AND
      METHODS: We report 13 novel cases of desmopressin associated water intoxication
      and review the literature. A total of 93 instances of symptomatic hyponatremia
      during desmopressin treatment in children were identified. Specific data were
      reported in 58 of 93 cases. These 58 cases, in addition to our 13 novel cases,
      were further analyzed. RESULTS: All children were treated with intranasal or
      intravenous desmopressin. No patient received oral desmopressin. Younger children
      are at greater risk for water intoxication than older children. The risk is
      particularly high at the beginning of desmopressin therapy. A total of 45
      patients (63%) had prodromal symptoms, eg nausea, vomiting and headache. In 10
      cases (14%) desmopressin was prescribed without an evident need. CONCLUSIONS:
      Based on this analysis, we conclude that the use of desmopressin should be
      cautiously considered, careful monitoring should be performed during the
      initiation of therapy, and particular care should be taken when treating young
      children and when prodromal symptoms such as nausea, vomiting and headaches
      occur.

PMID- 15947671
TI  - The colon flap/extension Malone antegrade continence enema: an alternative to the
      Monti-Malone antegrade continence enema.
AB  - PURPOSE: In situations where the appendix is not available for the Malone
      antegrade continence enema (MACE) procedure a Yang-Monti channel or a colon flap
      conduit can be created. We report our experience with colonic flap conduits used
      for the MACE. MATERIALS AND METHODS: A total of 169 MACE procedures were
      performed between February 1997 and March 2003. In 11 patients 12 colon flaps or
      cecal extensions were used to construct the MACE conduit. Diagnoses included
      myelomeningocele (8 patients), caudal regression (1), sacral agenesis (1) and
      gunshot wound (1). Mean age at creation of MACE was 11.3 years (range 4.4 to
      16.9). Seven cecal flaps, 1 descending colon flap and 4 cecal extension flaps
      were created. RESULTS: Average followup was 22.8 months (range 2.6 to 34.6).
      Indications for colon flap MACE were appendicovesicostomy (6 patients), short
      appendix (2), shortened mesentery (1), retrocecal appendix (1), prior
      appendectomy (1) and right hemicolectomy (1). Initially all patients easily
      catheterized and flushed the MACE once daily. All 11 patients achieved fecal
      continence. Complications occurred in 3 cases. One obese patient could not
      visualize the umbilical stoma and it stenosed, requiring conversion to a spiral
      Monti-MACE. One patient with a cecal extension had development of a false
      passage, resulting in complete channel stenosis. One patient had development of
      stomal leakage, which was successfully treated with dextranomer/hyaluronic acid
      copolymer injection. CONCLUSIONS: A colon flap MACE conduit is a simple technique
      to provide access to the colon for irrigation. When faced with situations were
      the appendix is not available for the MACE procedure the colon flap can be a good
      option.

PMID- 15947672
TI  - Renal pelvis volume during diuresis in children with hydronephrosis: implications
      for diagnosing obstruction with diuretic renography.
AB  - PURPOSE: We measured the volume of the renal pelvis during diuretic renography
      (DR) in children with normal and hydronephrotic kidneys to determine if changes
      in pelvic volume could affect the accuracy of DR in diagnosing obstruction.
      MATERIALS AND METHODS: We studied 18 patients 1 month to 10 years old with
      unilateral hydronephrosis ultimately proved to be either obstructive or
      nonobstructive. Simultaneous DR and ultrasound were performed with patients
      supine using the gamma camera. Ultrasound measurements of the renal pelvis in 3
      dimensions, obtained before and at intervals after diuretic injection, were used
      to calculate renal pelvic volume. The contralateral normal kidneys were used as
      controls. RESULTS: Between 15 and 60 minutes after diuretic injection the renal
      pelvis enlarged to a maximum volume in all hydronephrotic and normal kidneys and
      then gradually decreased in size. Mean average increase in volume for
      hydronephrotic kidneys ranged from 46% in obstructed kidneys to 88% in
      nonobstructed kidneys. Volume expansion caused dilution of isotope within the
      renal pelvis, which resulted in prolongation of elimination half-time (T1/2) in
      42% of nonobstructed hydronephrotic kidneys sufficient to register an obstructed
      washout pattern. However, there were no differences in the initial pelvic volume
      or the rate or extent of increases or decreases in pelvic volume that would
      permit nonobstructed hydronephrotic kidneys to be distinguished from obstructed
      ones. CONCLUSIONS: The renal pelvis enlarges during diuresis in children with
      hydronephrosis. This enlargement causes dilution of isotope within the renal
      pelvis during DR, which prolonged the isotope washout rate or T1/2 sufficiently
      to produce an obstructed washout pattern in more than 40% of hydronephrotic
      kidneys that were ultimately proved to be nonobstructed. This misdiagnosis of
      obstruction is particularly likely to occur in children younger than 2 years
      because pelvic volume expansion is so exaggerated. Consequently, T1/2 appears to
      be particularly vulnerable to inaccuracy in diagnosing obstruction in this age
      group, and, therefore, it should not be relied on as an operative determinant.

PMID- 15947680
TI  - Tumors of the male urethra.

PMID- 15947681
TI  - Symptomatic bladder lipomas.

PMID- 15947682
TI  - Water jet assisted laparoscopic partial nephrectomy without hilar clamping in the
      calf model.
AB  - PURPOSE: Hemostasis represents a primary challenge during laparoscopic partial
      nephrectomy (LPN). We typically clamp the renal artery/vein en bloc and perform
      LPN expeditiously under warm ischemia conditions. We evaluated Helix Hydro-jet
      assisted LPN without renal hilar vascular control in the survival calf model.
      MATERIALS AND METHODS: Staged bilateral LPN using the Hydro-jet was performed
      without renal hilar vessel control in 10 survival calves (20 kidneys).
      Parenchymal hydrodissection was performed with a high velocity, ultracoherent
      saline stream at 450 psi through a small nozzle with integrated suction at the
      tip. The denuded intrarenal parenchymal blood vessels were precisely coagulated
      with a BIClamp bipolar instrument and transected. Followup involved biochemical,
      radiological and histopathological evaluation at designated sacrifice intervals
      of 1 and 2 weeks, and 1, 2 and 3 months, respectively. RESULTS: All LPNs were
      completed successfully without open conversion. Of 20 LPNs 18 (90%) were
      performed without hilar clamping. Pelvicaliceal suture repair was necessary in 5
      of 10 chronic kidneys (50%). Mean Hydro-jet(R) partial nephrectomy time was 63
      minutes (range 13 to 150), mean estimated blood loss was 174 cc (range 20 to 750)
      and mean volume of normal saline used for hydro-dissection was 260 cc (mean 50 to
      1,250). No animal had a urinary leak. Histological sections from the acute
      specimen revealed a thin (1 mm) layer of adherent coagulum at the amputation site
      with minimal thermal artifact. At 2 weeks a layer of adherent fibro-inflammatory
      pseudomembrane with giant cell reaction was seen. CONCLUSIONS: In this more
      stringent and robust survival calf model Hydro-jet assisted LPN can be performed
      without hilar vessel control, thus, completely avoiding warm ischemia. This
      approach has the potential to decrease the level of technical difficulty inherent
      in LPN.

PMID- 15947683
TI  - Low dose suramin as a chemosensitizer of bladder cancer to mitomycin C.
AB  - PURPOSE: We have reported that acidic and basic fibroblast growth factors
      expressed in solid tumors induce broad-spectrum chemoresistance and their
      nonspecific inhibitor suramin (Sigma Chemical Co., St. Louis, Missouri) at
      nontoxic concentrations enhances the activity of chemotherapeutic agents. In the
      current study we evaluated whether low dose suramin enhances tumor sensitivity to
      mitomycin C (MMC) (Bristol-Myer Squibb Co., Wallingford, Connecticut). MATERIALS
      AND METHODS: Three-dimensional histocultures of RT4 (American Type Culture
      Collection, Rockville, Maryland) xenograft tumors and tumors from patients with
      bladder cancer were treated with MMC with or without 20 microM suramin. For in
      vivo studies mice bearing RT4 tumors received physiological saline, MMC (3
      mg/kg), suramin (10 mg/kg) or MMC/suramin combination every 3 or 4 days. Two MMC
      schedules were studied, namely subtherapeutic (3 treatments) and therapeutic (6
      treatments) schedules. RESULTS: Suramin enhanced MMC activity in xenograft and
      patient tumor histocultures by greater than 2-fold. The chemosensitization effect
      was observed in all patient tumors (2 superficial and 9 muscle invading lesions).
      In animals tumors in the control and suramin groups increased to approximately 3
      to 5 times the initial size. The subtherapeutic MMC schedule retarded tumor
      growth but did not produce tumor shrinkage, whereas the therapeutic MMC schedule
      reduced tumor size by 27%. The addition of suramin enhanced MMC activity.
      Respective tumor sizes were 40% and 63% of the sizes after subtherapeutic and
      therapeutic MMC alone (p <0.01). The combination groups showed body weight losses
      similar to those of MMC alone. CONCLUSIONS: Low dose suramin enhanced the in
      vitro and in vivo activity of subtherapeutic and therapeutic MMC without
      enhancing host toxicity, thus, providing proof of concept for evaluating low dose
      suramin as a chemosensitizer with MMC in bladder cancer.

PMID- 15947684
TI  - Vascular endothelial growth factor antisense pretreatment of bladder cancer cells
      significantly enhances the cytotoxicity of mitomycin C, gemcitabine and
      Cisplatin.
AB  - PURPOSE: Due to unsatisfactory success in the treatment of local and systemic
      bladder cancer and the low response rates to commonly used chemotherapy (CT)
      alternative and additive approaches must be found. The function of vascular
      endothelial growth factor (VEGF) in neo-angiogenesis and, therefore, in solid
      tumors makes it a promising target for a specific antitumor therapy. We
      investigated the possibility of sensitizing transitional bladder cancer cell
      lines to CT by pretreatment with VEGF antisense (AS) oligodeoxynucleotides (AS
      ODNs). MATERIALS AND METHODS: The human bladder cancer cell lines EJ28 and 5637
      were transiently transfected with 3 antiVEGF AS-ODNs, followed by incubation with
      3 doses of mitomycin C, gemcitabine or cisplatin CT. WST-1 (a sodium salt of 4-[3
      (4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate) assay
      (Roche, Mannheim, Germany) was performed to assess effects on cell viability.
      Apoptosis was examined by Annexin V staining. In all experiments a nonsense ODN
      served as a control. RESULTS: Each cell line responded in a dose dependent manner
      to all CTs. Combined treatment with VEGF AS-ODNs and CT resulted in decreased
      viability compared with isolated CT. VEGF857 plus CT significantly decreased the
      viability of the 2 cell lines compared with nonsense ODN plus CT for all 3 CT
      agents (p <0.007). This detected chemosensitization was based on an AS mediated
      increase in apoptosis. CONCLUSIONS: One of the 3 AS-ODNs tested (VEGF857)
      significantly sensitizes human transitional cell carcinoma cells to CT. We
      suggest VEGF as an additional putative target to enhance the therapeutic benefit
      of, for example mitomycin C and gemcitabine instillation treatment schedules.

PMID- 15947685
TI  - Cyclooxygenase-2 inhibition: a potential mechanism for increasing the efficacy of
      bacillus calmette-guerin immunotherapy for bladder cancer.
AB  - PURPOSE: Intravesical bacillus Calmette-Guerin (BCG) therapy is the principal
      treatment for high risk, noninvasive urothelial carcinoma and carcinoma in situ
      of the bladder. However, up to 40% of patients fail to respond to this treatment.
      In this study the potential for inhibition of PGE2 production by BCG treated
      dendritic cells (DCs) was studied in the context of preferential polarization of
      the immune response toward a cancer clearing T-helper type 1 immune response.
      MATERIALS AND METHODS: Murine bone marrow derived DCs were cultured with
      interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. After 7
      days the cells were stimulated with BCG. Cell surface expression of co
      stimulatory molecules and phagocytic ability were measured by flow cytometry
      analysis to verify cell activation. The production of IL-10 and IL-12 was
      measured after DC stimulation with BCG in the presence of IL-10, prostaglandin
      E2(Cayman Chemical, Ann Arbor, Michigan), antiIL-10 antibody (Insight
      Biotechnology, Wembley, United Kingdom), NS-398 and indomethacin (Sigma, Poole,
      United Kingdom). RESULTS: Prostaglandin E2 stimulated a dose dependent increase
      in the levels of IL-10 produced by BCG activated DCs (p <0.01). IL-10
      significantly decreased IL-12 production (p <0.001), while IL-10 blockade
      significantly increased IL-12 levels (p <0.05). The COX-2 selective inhibitor NS
      398 caused a dose dependent increase in the concentration of IL-12 produced by
      BCG activated DCs (p <0.01). This effect was also seen with the partially
      selective COX-1 inhibitor indomethacin (p <0.05). CONCLUSIONS: The inhibition of
      PGE2 synthesis by COX inhibition favored the production of IL-12 by BCG activated
      DC. This potentially will result in the generation of a T-helper type 1,
      polarized T-cell response that may improve the efficacy of BCG therapy.

PMID- 15947686
TI  - Macrophage migration inhibitory factor is released as a complex with alpha1
      inhibitor-3 in the intraluminal fluid during bladder inflammation in the rat.
AB  - PURPOSE: Macrophage migration inhibitory factor (MIF) is released into
      intraluminal fluid (ILF) during bladder inflammation in the rat. We investigated
      the forms of MIF that are released. We examined MIF release after subcutaneous
      substance P (SP) or intravesical capsaicin and studied proteins associated with
      excreted MIF in ILF. MATERIALS AND METHODS: Anesthetized male rats with the
      bladder isolated from the kidneys were injected with SP subcutaneously (saline
      vehicle) or with intravesical capsaicin (vehicle, 0.1 mM and 1 mM). After 1 hour
      the ILF was removed and MIF levels were determined using enzyme-linked
      immunosorbent assay or Western blotting procedures under native, nonreducing and
      reducing conditions. Mass spectrometry was used to identify proteins associated
      with MIF in ILF and results were verified by immunoprecipitation. RESULTS: SP and
      intravesical capsaicin increased the total amount of MIF in ILF. MIF was found in
      high molecular weight complexes that resolved into 2 bands under nonreducing
      conditions. SP and capsaicin differentially increased the MIF bands. Mass
      spectrometry determined that MIF was complexed with acute phase proteins. MIF
      immunoprecipitation followed by Western blotting confirmed that MIF was complexed
      to alpha1-inhibitor-3. CONCLUSIONS: MIF is complexed with alpha1-inhibitor-3, a
      member of the alpha-2-macroglobulin proteinase inhibitor family, in the rat.
      Although SP and capsaicin increased the total amount of MIF detected by enzyme
      linked immunosorbent assay in ILF, the patterns of MIF complexes elicited by
      these 2 treatments were different. These findings suggest that in association
      with other proteins MIF forms part of a complex elicited by bladder inflammation.

PMID- 15947687
TI  - Urinary uronate and sulfated glycosaminoglycan levels: markers for interstitial
      cystitis severity.
AB  - PURPOSE: Urologists frequently rely on symptom and problem indexes to monitor
      patients with interstitial cystitis (IC). Uronic acid is a component of most
      glycosaminoglycans (GAGs), which is a protective bladder urothelium coating. We
      evaluated whether urinary uronate and sulfated GAG levels correlate with IC
      severity and we characterized urinary GAG species. MATERIALS AND METHODS: Urine
      samples, and a completed O'Leary-Sant IC symptom and problem index questionnaire
      were obtained from 37 patients with IC and 14 normal individuals. Patients with
      IC were in group 1-1 or 2 indexes less than 50% the maximum score or group 2-each
      index 50% or greater the maximum score. All patients fulfilled National Institute
      of Diabetes and Digestive and Kidney Diseases criteria except glomerulations.
      Urinary uronate was fractionated using cetyltrimethylammonium bromide (CETAB).
      Uronate and sulfated GAG levels in urine, CETAB precipitates and CETAB
      supernatants were measured by the Bitter and Muir, and Farndale assays,
      respectively, and normalized to creatinine in microg/mg creatinine. GAG species
      were analyzed by agarose gel electrophoresis. RESULTS: Mean urinary uronate
      levels were increased in group 2 compared with normal and group 1 values
      regardless of glomerulations and treatment (1,614 +/- 904.6 vs 612.4 +/- 327.2
      and 593.8 +/- 422.1 microg/mg creatinine, respectively, p <0.001). A small
      portion of urinary uronate was CETAB precipitable, representing macromolecular
      GAGs. Uronate levels in CETAB precipitates and CETAB supernatants were
      approximately 2.8-fold increased in group 2 (8.0 +/- 5.07 and 1,393 +/- 671.9
      microg/mg creatinine, respectively) compared with normal and group 1 values (p
      <0.001), and they contained fast and slow moving GAG species. Uronate and
      sulfated GAG had 80% and 88% sensitivity, and 92.3% and 69.2% specificity,
      respectively, to detect IC severity. CONCLUSIONS: The majority of urinary GAGs
      likely exist as small oligosaccharides. Urinary uronate and sulfated GAG levels
      are increased in patients with IC who have severe disease. They may become useful
      markers for monitoring IC.

PMID- 15947688
TI  - Retrograde renal cooling during radio frequency ablation to protect from renal
      collecting system injury.
AB  - PURPOSE: We evaluated the protective effect of continuous retrograde irrigation
      of ice-cold saline on the renal collecting system during central parenchymal
      temperature based radio frequency ablation (RFA). MATERIALS AND METHODS: In 10
      domestic pigs bilateral, centrally located renal parenchymal RFA lesions
      (intended 2 cm in diameter) were created that intentionally involved the
      collecting system. RFA probe placement was guided by fluoroscopy with retrograde
      collecting system opacification and simultaneous direct laparoscopic
      visualization. In 1 renal unit RFA was performed while infusing ice-cold saline
      through a previously placed ureteral access sheath and pigtail stent. RFA without
      renal cooling was performed in the contralateral renal unit. Kidneys were
      harvested at 7 days. The renal collecting system was inspected for injury by
      performing retrograde pyelograms and by histological examination of the
      collecting system adjacent to the ablation zone. The size of RFA lesions was
      measured. RESULTS: In retrograde cooling procedures the temperature of saline
      irrigant was -1.0C and the mean temperature of the effluent was 13C. One of 10
      cooled renal units demonstrated contrast material extravasation from the
      collecting system involved by the ablation zone compared with 7 of 10 noncooled
      renal units (p = 0.025). Lesion size was comparable between cooled kidneys and
      controls (2.67 and 2.72 cm, respectively, p = 0.629). CONCLUSIONS: Retrograde
      renal cooling helps protect the renal collecting system from injury during RFA
      without a decrease in expected lesion size. Clinically retrograde renal cooling
      may decrease the risk of collecting system injury and subsequent complications
      during RFA.

PMID- 15947689
TI  - Bladder reconstitution with bone marrow derived stem cells seeded on small
      intestinal submucosa improves morphological and molecular composition.
AB  - PURPOSE: Tissue engineering has been used for bladder augmentations with small
      intestinal submucosa (SIS). Although favorable short-term outcomes have been
      reported, long-term followup has been poor. We investigate whether tissue
      engineering with stem cells improves the morphological and genetic composition.
      MATERIALS AND METHODS: A total of 33 Lewis rats (Harlan Laboratories,
      Indianapolis, Indiana) were used to investigate bladder augmentations with 4
      layer SIS in certain groups, including the control group (sham operation),
      partial cystectomy with oversewn defect group (OG), augmentation with unseeded
      SIS group (USG) and augmentation with stem cell seeded SIS group (SSG). Bladders
      from 4 rats per group were harvested 1 and 3 months after surgery. Morphological
      analyses were performed using Masson's trichrome and immunohistochemical staining
      with cytokeratin AE1/AE3, smooth muscle alpha-actin and S100. Gene expression was
      evaluated using quantitative real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) for collagen I (CI), collagen III (CIII), cytokeratins 8 and
      19, and smooth muscle myosin heavy chain (MHC). RESULTS: At 1 month trichrome
      staining revealed collagen admixed with indiscrete cells and morphology similar
      to that in controls in USG and SSG, respectively. Discrete smooth muscles
      fascicles and S100 staining were found in all groups except USG. Organized
      urothelium with increased basal cell layer staining was present in controls and
      SSG only. At 3 months increased collagen formation was present in OG and USG.
      Immunostaining showed hyperplasia of the urothelium with increased staining of
      the basal cell layer, discrete muscle fascicles and positive nerve staining in
      all groups. Using quantitative RT-PCR expression levels in SSG were more improved
      than in USG, especially for CI, CIII and MHC. This was further evident at 3
      months when CI and CIII were over expressed in OG and USG but not in the control
      group or SSG. Furthermore, RT-PCR showed that cytokeratins 8 and 19, and MHC had
      greater expression levels in SSG than in USG. CONCLUSIONS: Bladder reconstitution
      occurs more rapidly using stem cell seeded SIS. Although in USG and SSG all 3
      cellular constituents appear to develop by 3 months, only SSG had gene expression
      levels similar to those in controls. The results suggest an explanation for the
      fibrosis noted in unseeded SIS bladder augmentations and the possible solution
      using stem cells.

PMID- 15947690
TI  - Over expression of smooth muscle thin filament associated proteins in the bladder
      wall of diabetics.
AB  - PURPOSE: The thin filament associated proteins caldesmon, tropomyosin and
      calponin have been shown to modulate actin-myosin interaction, actomyosin
      adenosine triphosphatase and contraction in smooth muscle. This study was
      performed to determine whether the expression of these proteins is altered in
      diabetes induced decrease in the contractility of bladder wall smooth muscle.
      MATERIALS AND METHODS: Detrusor samples were obtained from New Zealand White male
      rabbits with alloxan induced diabetes, and from age and sex matched control
      rabbits. In addition, a bladder myocyte cell line, which continues to express
      smooth muscle phenotype, was exposed to either normal (5 mM) or high (50 mM)
      concentrations of glucose. The levels of expression of the thin filament
      associated proteins were determined at the mRNA and protein levels by reverse
      transcriptase-polymerase chain reaction and Western blotting, respectively.
      RESULTS: Detrusor smooth muscle tissue from rabbits with alloxan induced diabetes
      showed over expression of thin filament associated proteins, calponin,
      tropomyosin and caldesmon when compared with that of the control. Similar up
      regulation was seen also in bladder myocytes in cultures treated with 50 mM
      glucose, indicating that the high glucose induced the changes. CONCLUSIONS: Our
      results suggest that the increased expression of thin filament proteins,
      calponin, tropomyosin and caldesmon in diabetic rabbits might alter the
      contractile and cytoskeletal structure in bladder myocytes. The over expression
      of these thin filament associated proteins, which suppresses actin-myosin
      interaction and actomyosin adenosine triphosphatase, and the enhancement of this
      suppression by tropomyosin are likely to have an effect on the relationship
      between force and myosin light chain phosphorylation, requiring higher levels of
      phosphorylation in diabetic detrusor compared with that of control. The
      downstream effects of high glucose (eg oxidative stress) appear to modulate the
      transcriptional regulation of thin filament mediated regulatory proteins in
      bladder smooth muscle.

PMID- 15947691
TI  - Role of cyclooxygenase-2 in the development of bladder overactivity after
      cerebral infarction in the rat.
AB  - PURPOSE: We investigated the role of cyclooxygenase (COX) isoforms in bladder
      overactivity induced by cerebral infarction (CI) in rats. MATERIALS AND METHODS:
      CI was induced by left middle cerebral artery occlusion (MCAO) in female Sprague
      Dawley rats. Bladder activity was monitored with continuous infusion
      cystometrography of conscious rats. Specimens were obtained from the pontine
      tegmental area (PTA) 1, 3, 5, 12 and 24 hours after CI or sham operation (SO).
      The effects of MK-801 (0.1 mg/kg intravenously), an NMDA (N-methyl-D-aspartate)
      glutamatergic receptor antagonist, on bladder activity, and on COX-1 and 2 mRNA
      expression following MCAO were examined. Real-time quantitative reverse
      transcriptase-polymerase chain reaction was performed to evaluate the effects of
      CI on gene expression in the PTA. The effects of the COX-2 inhibitor NS398 (0.01
      to 10 mg/kg intravenously) on bladder activity were examined. RESULTS: The
      bladder capacity of CI rats was significantly decreased 1 to 24 hours after MCAO
      compared with that of SO rats (p <0.05 or 0.01). One and 3 hours after MCAO mean
      COX-2 mRNA expression +/- SE had increased significantly to 22.4 +/- 3.5 in terms
      of its expression relative to the outer control in a sample obtained immediately
      after MCAO, in contrast to that in SO rats (p <0.01). The expression level
      returned to the control level within 12 hours after MCAO. COX-1 expression was
      not influenced by MCAO. Pretreatment with MK-801 inhibited the development of
      bladder overactivity and significantly decreased the expression of COX-2 mRNA in
      the PTA (p <0.01). Treatment with NS398 before MCAO prevented the development of
      bladder overactivity in a dose dependent manner and did not influence infarct
      volume. CONCLUSIONS: These results indicate that the development of bladder
      overactivity following MCAO is accompanied by an increase in COX-2 mRNA
      expression in the PTA and is mediated by NMDA receptor activity. COX-2 in the
      brain may be a new target for the treatment of neurogenic voiding dysfunction
      after cerebral infarction.

PMID- 15947692
TI  - Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor.
AB  - PURPOSE: alpha1-Adrenoceptor (AR) blockers are known to relieve not only voiding
      symptoms, but also storage symptoms in elderly men. We investigated lower urinary
      tract function in mice lacking alpha1d-AR using frequency/volume analysis and
      filling cystometry. MATERIALS AND METHODS: A total of 10, 12-week-old female
      alpha1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were
      studied. Each mouse was placed in a metabolic cage connected to a digital scale
      and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency
      and volume were recorded for 48 hours. After frequency/volume analysis filling
      cystometry was performed with the mice awake and without restraint. The
      expression of alpha1-AR subtype mRNA in the bladder of mice in each group was
      quantified using real-time polymerase chain reaction. RESULTS: Mean daily voiding
      frequency +/- SD in alpha1d-KO mice was 9.0 +/- 2.1, significantly lower than
      15.9 +/- 5.2 in WT mice (p = 0.0048). Mean volume per void in alpha1d-KO mice was
      significantly larger than in WT mice (0.24 +/- 0.02 vs 0.16 +/- 0.03 ml, p =
      0.0096). Similarly cystometric analysis demonstrated larger bladder capacity
      (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in alpha1d-KO mice
      compared with those in WT mice. No significant difference in maximum pressure at
      void was observed between the 2 groups. In WT mice the amount of alpha1a, alpha1b
      and alpha1d-AR subtype mRNA in the bladder was 5.2 +/- 0.7, 1.0 +/- 0.1 and 6.3
      +/- 0.7 gene copies per ng total RNA, respectively. In contrast, alpha1d-AR
      transcript was not detectable in alpha1d-KO mice but alpha1a and alpha1b-AR
      expression was similar to that in WT mice. CONCLUSIONS: The results demonstrate
      that the alpha1d-AR subtype has an important role in regulating bladder function.
      They theoretically support a clinical finding that alpha1-blockers with
      significant affinity for alpha1d-AR are effective for treating storage symptoms
      associated with benign prostatic obstruction.

PMID- 15947693
TI  - Benign prostatic hyperplasia cell line viability and modulation of jm-27 by
      doxazosin and Ibuprofen.
AB  - PURPOSE: Benign prostatic hyperplasia (BPH) is among the most common diseases
      affecting quality of life in older men. Despise intense research efforts to our
      knowledge the genetic mechanisms underlying the BPH disease process and
      therapeutic markers needed to determine patient responsiveness to a particular
      form of pharmacological therapy are still not identified. This has slowed the
      development of new therapeutic agents for the treatment of BPH. MATERIALS AND
      METHODS: We investigated the cellular effects of certain drugs on BPH. Besides
      doxazosin, which is the prevailing drug to treat BPH, the effect of ibuprofen was
      examined as a new therapeutic approach due to strong evidence of a correlation
      between BPH and inflammation. RESULTS: This study showed that doxazosin as well
      as ibuprofen significantly decreases cell viability and induced apoptosis in 267
      B1 cells as well as in BPH-1 cells. In addition, we observed that the
      administration of doxazosin and ibuprofen to BPH-1 cells decreased the expression
      of JM-27, a protein particularly expressed in prostate that is highly up
      regulated in symptomatic BPH. CONCLUSIONS: Our findings suggest that ibuprofen
      may be a new therapeutic target for the treatment of BPH. Further research must
      be done to investigate the potential use of ibuprofen in patients with BPH and
      examine if JM-27 expression in patients with BPH may stratify individuals who may
      be most responsive to pharmacological treatment.

PMID- 15947694
TI  - Induction of the urothelial differentiation program in the absence of stromal
      cues.
AB  - PURPOSE: The urothelial stroma is presumed to have a critical role in the
      formation and homeostasis of normal urothelium. To determine the intrinsic
      capacity of urothelial cells to initiate urothelial differentiation human
      urothelial cell were cultured under conditions that promote differentiation in
      the absence of stromal signaling. MATERIALS AND METHODS: Immortalized and primary
      human urothelial cells were cultured in semisolid medium. Recovered cells were
      then analyzed by immunofluorescence, flow cytometry and immunoblotting for
      expression of the differentiation specific keratins K18 and K8, and cyclin-cyclin
      dependent kinase inhibitors. The expression of these markers in cells following
      semisolid culture was then compared with that in normal bladder and ureteral
      mucosa as well as in synthetic urothelium generated by 3-dimensional organotypic
      raft cultures. RESULTS: Organotypic raft culture of primary and immortalized
      urothelial cells generated full-thickness epithelium that resembled human bladder
      and ureteral urothelium, and expressed K8 and K18 in superficial layers.
      Suspension culture in semisolid medium induced K18 expression approximately 9
      fold at 24 hours. p21 and p27 expression were induced by 6 hours and yet p21
      expression subsided within 12 hours, while p27 expression persisted. CONCLUSIONS:
      These results indicate that primary and immortalized human urothelial cells have
      the capacity to enter the urothelial differentiation program and such entry does
      not require inductive signals from stroma. Furthermore, these data suggest that
      p21 and p27 have distinct roles in regulating the urothelial cell cycle.

PMID- 15947695
TI  - Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of
      antioxidants.
AB  - PURPOSE: We searched for markers of oxidative stress in cavernous ischemia and
      examined the effect of long-term antioxidant intake on arteriogenic erectile
      dysfunction (ED) in the rabbit. MATERIALS AND METHODS: Antioxidant activity of
      known antioxidant beverages, such as pomegranate juice (PJ), red wine, blueberry
      juice, cranberry juice, orange juice and green tea, was examined
      spectrophotometrically. PJ demonstrated the highest free radical scavenging
      capacity. The effect of long-term PJ intake on intracavernous blood flow and
      penile erection was then examined in the rabbit model. Erectile tissues were
      processed to assess oxidative stress and smooth muscle relaxation,
      immunohistochemical staining of nitric oxide synthase (NOS) and histomorphometry.
      RESULTS: On spectrophotometric analysis PJ showed the highest capacity to
      decrease low density lipoprotein oxidation and inhibit cellular oxidative stress
      in macrophages. The rabbit model of arteriogenic ED demonstrated decreased
      intracavernous blood flow, erectile dysfunction, loss of smooth muscle
      relaxation, decreased endothelial NOS and neuronal NOS, increased inducible NOS
      expression, diffused cavernous fibrosis and increased cavernous levels of the
      oxidative product isoprostane 8-epi-prostaglandin F2alpha. Long-term PJ intake
      increased intracavernous blood flow, improved erectile response and smooth muscle
      relaxation in ED and control groups while having no significant effect on NOS
      expression. PJ intake prevented erectile tissue fibrosis in the ED group.
      CONCLUSIONS: Arteriogenic ED accumulates oxidative products in erectile tissue,
      possibly via an intrinsic mechanism. Oxidative stress may be of great importance
      in the pathophysiology of arteriogenic ED. Antioxidant therapy may be a useful
      prophylactic tool for preventing smooth muscle dysfunction and fibrosis in ED.

PMID- 15947699
TI  - Re: Cytoreductive nephrectomy in patients with metastatic renal cancer: a
      combined analysis.

PMID- 15947701
TI  - Re: The relationship between renal tumor size and metastases in patients with von
      Hippel-Lindau disease.

PMID- 15947702
TI  - Re: Editorial comment on interim outcomes of dorsal skin graft bulbar
      urethroplasty.

PMID- 15947703
TI  - Re: Erosion of a male polypropylene sling.

PMID- 15947706
TI  - Re: Alfuzosin once daily facilitates return to voiding in patients in acute
      urinary retention.

PMID- 15947709
TI  - Re: Health related quality of life before and after laparoscopic radical
      prostatectomy.

PMID- 15947712
TI  - The human gene map for performance and health-related fitness phenotypes: the
      2004 update.
AB  - We began this series in 2000 with the aim of making available in an easily
      accessible format all the advances on the genetic basis of a large family of
      exercise-related traits. The current review presents the 2004 update of the human
      gene map for physical performance and health-related fitness phenotypes. It is
      based on peer-reviewed papers published by the end of 2004. The genes and markers
      with evidence of association or linkage with a performance or fitness phenotype
      in sedentary or active people, in adaptation to acute exercise, or for training
      induced changes are positioned on the genetic map of all autosomes and the X
      chromosome. Negative studies are reviewed but a gene or locus must be supported
      by at least one positive study before being inserted on the map. One new feature
      is that we have incorporated the genes whose sequence variants have been
      associated with either the level of physical activity or indicators of
      sedentarism. By the end of 2000, in the early version of the gene map, 29 loci
      were depicted. In contrast, the 2004 human gene map for physical performance and
      health-related phenotypes includes 140 autosomal gene entries and quantitative
      trait loci, plus four on the X chromosome. Moreover, there are 16 mitochondrial
      genes in which sequence variants have been shown to influence relevant fitness
      and performance phenotypes. Thus, the map is growing in complexity and progress
      is being made. The number of laboratories and scientists concerned by the role of
      genes and sequence variations in exercise-related traits is rising. But exercise
      science and sports medicine is generally lagging behind in terms of utilizing the
      advances in genetic and genomic technologies.

PMID- 15947713
TI  - Dietary salt, airway inflammation, and diffusion capacity in exercise-induced
      asthma.
AB  - PURPOSE: Recent studies have supported a role for dietary salt as a modifier of
      the severity of exercise-induced asthma. The main aim of this study was to
      demarcate a possible mechanism by which dietary salt modification may alter
      exercise-induced airway narrowing in asthmatic patients. METHODS: Twenty-four
      patients participated in a randomized, double-blind crossover study. Subjects
      entered the study on their normal salt diet (NSD) and were then placed on either
      a low-salt diet (LSD) or high-salt diet (HSD) for 2 wk with a 1-wk washout period
      occurring between diets. Pre- and postexercise spirometry, pulmonary diffusion
      capacity (DLCO) and its subdivisions, and induced sputum were obtained on the NSD
      and at the end of each 2-wk treatment period (LSD and HSD). RESULTS: FEV1
      decreased by 7.9 +/- 2.8% on LSD, 18.3 +/- 4.0% on NSD, and 27.4 +/- 3.2% on HSD
      at 20 min postexercise. The NSD and HSD induced significant reductions (P < 0.05)
      in DLCO and its subdivisions. However, postexercise pulmonary capillary blood
      volume significantly increased (P < 0.05) by 6.3 and 9.6 mL on NSD and HSD,
      respectively, compared with baseline values, with no significant change (P >
      0.05) being observed on LSD. Postexercise-induced sputum neutrophil and
      eosinophil differential cell counts and induced sputum supernatant concentration
      of eosinophil cationic protein, interleukin (IL)-1beta, IL-8, leukotriene (LT)
      C(4)-E(4), LTB(4), and prostaglandin D(2) were significantly elevated (P < 0.05)
      on NSD and HSD compared with LSD. CONCLUSION: Our findings indicate that dietary
      salt loading enhances airway inflammation following exercise in asthmatic
      subjects, and that small salt-dependent changes in vascular volume and
      microvascular pressure might have substantial effects on airway function
      following exercise in the face of mediator-induced increased vascular
      permeability.

PMID- 15947714
TI  - Muscle oxygenation of the paralyzed lower limb in spinal cord-injured persons.
AB  - PURPOSE: Even in the paralyzed lower limb muscle, EMG activity can be induced by
      imposing passive leg movement in standing posture in persons with spinal cord
      injury (SCI). The purpose of the present study was to ascertain whether the
      oxygenation level of the paralyzed lower limb muscle covaried with the muscle EMG
      activity during imposed passive leg movement. METHODS: Six motor-complete SCI
      subjects and four neurologically normal controls were placed on a gait-training
      apparatus that enabled the SCI subjects to stand and move their legs passively.
      After a 1-min resting stage, consecutive passive alternate leg movements were
      performed at different frequencies (0.8, 1, 1.2, and 1 Hz, for 3 min at each
      stage). To obtain postexercise data, subjects were kept in a standing posture for
      5 min after passive movement ceased. The EMG activity and concentration changes
      in the oxygenated (oxy-) and deoxygenated hemoglobin (Hb) (deoxy-Hb) were
      continuously measured using near-infrared spectroscopy (NIRS) from the
      gastrocnemius muscle. RESULTS: In all SCI subjects, muscle EMG activity was
      observed during passive leg movement. The oxy-Hb level gradually increased,
      whereas the deoxy-Hb decreased, and these changes were independent of the total
      Hb changes. In the recovery stage, the total Hb level was found to exceed the
      preexercise level. In contrast to the SCI patients, the normal subjects showed
      neither EMG activity nor changes in oxy- or deoxy-Hb. CONCLUSION: The present
      results demonstrate that passive leg movement can induce not only muscular
      activity but also alteration of muscle oxygenation level in the paralyzed lower
      leg. Particularly, induced muscular activity seems to correlate with increased
      perfusion of the muscle.

PMID- 15947715
TI  - Cardiovascular fitness and the metabolic syndrome in overweight latino youths.
AB  - PURPOSE: To determine whether cardiovascular fitness (.)VO(2max) is associated
      with the metabolic syndrome and its individual features in overweight Latino
      youths. METHODS: A total of 163 overweight Latino boys and girls (body mass index
      (BMI) percentile = 97.0 +/- 3.1; age = 11.2 +/- 1.7 yr) with a family history of
      Type 2 diabetes participated in this investigation. The metabolic syndrome was
      defined as having three or more of the following risk factors: abdominal obesity,
      high blood pressure, low HDL-cholesterol, high triglycerides, and impaired
      glucose tolerance. (.)VO(2max) was determined by a progressive treadmill test to
      exhaustion, and body composition was assessed using dual energy x-ray
      absorptiometry. RESULTS: (.)VO(2max) was not correlated with any individual risk
      factor of the metabolic syndrome after adjusting for gender, age, and body
      composition in partial analysis. Furthermore, ANCOVA revealed that children with
      zero, one, two, or three or more risk factors did not differ in regards to
      fitness levels. CONCLUSION: (.)VO(2max) is not independently associated with the
      metabolic syndrome or any individual feature in overweight youths of Latino
      ethnicity after controlling for differences in confounding variables.

PMID- 15947716
TI  - Warm-up stretches reduce sensations of stiffness and soreness after eccentric
      exercise.
AB  - PURPOSE: A commonly used method for warm-up before exercise is to stretch
      muscles. How this benefits performance remains uncertain. After a period of
      eccentric exercise, there is muscle damage accompanied by an increase in passive
      tension, perceived as a sensation of increased stiffness in the exercised
      muscles. We have tested the idea that warm-up stretches might reduce levels of
      passive tension to reduce sensations of stiffness and soreness after eccentric
      exercise. METHODS: Subjects eccentrically exercised elbow flexors of one arm on
      an isokinetic dynamometer. The other arm acted as a control. After the exercise,
      measurements were made of resting elbow angle, as an indication of passive
      tension levels, before and after one or five large, passive arm extensions.
      Additional measurements made at 24 h included soreness levels in response to
      muscle stretch or vibration. RESULTS: After the exercise, the relaxed elbow
      adopted a more flexed posture than normal, an effect that slowly subsided over
      the next 4 d. Five rapid arm extensions returned arm posture back to near control
      levels. The flexed posture then gradually re-developed over the next hour. At 24
      h postexercise, extending the arm produced some soreness as did muscle vibration.
      The pain from arm extension and vibration was reduced after a series of arm
      extensions. CONCLUSIONS: The flexed posture at the elbow is due to an increase in
      passive tension in elbow flexors as a result of muscle damage from the eccentric
      exercise. Stretch reduces passive tension. Benefits from the lower tension are
      reduced sensations of stiffness and soreness. This represents a new proposal for
      the mechanism for passive stretches as a warm-up strategy.

PMID- 15947717
TI  - ATP economy of force maintenance in human tibialis anterior muscle.
AB  - PURPOSE: The aim of this study was investigate ATP economy of force maintenance
      in the human tibialis anterior muscle during 60 s of anaerobic voluntary
      contraction at 50% of maximum voluntary contraction (MVC). METHODS: ATP turnover
      rate was evaluated using P magnetic resonance spectroscopy (P-MRS). The total
      volume of ankle dorsiflexor muscles was assessed by H magnetic resonance imaging
      (MRI) (H-MRI), and the fiber type composition of the tibialis anterior muscle was
      evaluated using histochemical analysis of muscle biopsies. RESULTS: The tibialis
      anterior muscle occupied 59.7 +/- 0.6% (mean +/- SEM) of the total ankle
      dorsiflexor muscle volume, which was 267 +/- 10 cm. Relative cross-sectional
      areas occupied by Type I, IIA, and IIB fibers in the tibialis anterior were 69.3
      +/- 2.2, 27.4 +/- 2.76, and 3.2 +/- 1.0%, respectively. ATP economy of force
      maintenance did not change significantly during the 60-s contraction. It averaged
      at 4.81 +/- 0.42 N.s.micromol-1, and correlated with the relative cross-sectional
      area of the muscle occupied by Type I fiber (r = 0.73, P < 0.01). For the second
      half of the contraction, subjects dropping in force showed lower ATP economy
      compared with those maintaining the force (3.7 +/- 0.6 vs 5.3 +/- 0.6
      N.s.micromol-1; P < 0.05). CONCLUSION: It is argued that the unchanged ATP
      economy of force maintenance during the voluntary contraction could be due to an
      increase in the ATP economy of contracting muscle fibers offsetting the effects
      of increased temperature and low ATP economy of Type II fibers. Mechanical
      interaction between motor units could also act to improve ATP economy of force
      maintenance.

PMID- 15947718
TI  - Circulating angiotensin converting enzyme activity is correlated with muscle
      strength.
AB  - PURPOSE: The D-variant of the angiotensin-1 converting enzyme (ACE) gene is
      associated with higher circulating and tissue ACE activity. Some studies have
      suggested a similar association of genotype with muscle strength or the gain in
      strength in response to training. This study has assessed the relationship
      between circulating ACE activity, strength, and the response to training.
      METHODS: Eighty-one untrained men were tested for quadriceps muscle strength, and
      44 of these performed an 8-wk program of dynamic strength training of the
      quadriceps muscle group. Venous blood was obtained for assessment of circulating
      ACE activity before and after the training program. ACE genotype was also
      determined. RESULTS: At baseline, circulating ACE activity was significantly
      correlated with isometric (r = 0.25-0.29, P < 0.02) and isokinetic (r = 0.38, P <
      0.0005) quadriceps muscle strength. ACE genotype also seemed to be related to
      pretraining muscle strength. However, circulating ACE activity showed no
      significant association with the 9-14% mean increases of muscle strength in
      response to the training intervention. ACE genotype also showed no association
      with the training-induced change in muscle strength. Circulating ACE activity did
      not change significantly after the training program. CONCLUSIONS: The data
      support a role for ACE in the regulation of human skeletal muscle strength, but
      do not confirm a role in altering the response to short-term training.

PMID- 15947719
TI  - Transient decrease of neutrophil chemotaxis following aerobic exercise.
AB  - PURPOSE: Intense exercise affects the immune system, increasing the
      susceptibility of athletes to viral and bacterial infections. We have previously
      shown a significant decrease of fMLP-neutrophil migration 24 h after aerobic
      exercise. In this study we aimed to look at the differential effect of different
      chemoattractants on neutrophil migration following aerobic exercise, to determine
      the recovery time, and to better understand the role of the cell skeleton behind
      the impaired chemotaxis. METHODS: Sixteen female volunteers aged 22-30 yr were
      tested before, 24, and 48 h after aerobic exercise (30 min running at 70%
      (.)VO(2max). The submaximal exercise test was conducted a week after the
      (.)VO(2max) test. We studied the membrane cell receptor response to fMLP, IL-8,
      and C5a, which have specific ligand-receptor pathways. Further, we studied the
      cytoskeletal response by investigating the cell polarization and the F-actin
      polymerization. RESULTS: Significant decrease of the neutrophil net chemotaxis
      was detected with fMLP, IL-8 and C5a, 24 h after exercise (50 +/- 5%, P = 0.0001;
      48 +/- 12%, P = 0.0015; and 32 +/- 11%, P = 0.011, respectively). Complete
      recovery was observed within 48 h with all chemoattractants. Normal neutrophil
      random migration and F-actin polymerization were found. Decreased neutrophil
      polarization was detected (46 +/- 6% vs 22 +/- 8% of polarized cells, before and
      after effort, respectively; P = 0.004). Correlation between polarization and
      chemotactic migration was found (r = 0.945; P = 0.001). CONCLUSIONS: The impaired
      chemotactic response, observed 24 h after exercise, was similar using different
      chemoattractants. This finding indicates a possible exercise-induced effect on a
      common factor at the ligand-receptor level. The abnormal cell polarization
      indicates skeletal dysfunction that should be further investigated and
      elucidated. The normal fMLP-stimulated-F-actin polymerization reflects an
      adequate pathway of signal transduction for the formyl peptide.

PMID- 15947720
TI  - The impact of metabolic stress on hormonal responses and muscular adaptations.
AB  - PURPOSE: The purpose of this study was to examine the impact of exercise-induced
      metabolic stress on hormonal responses and chronic muscular adaptations. METHODS:
      We compared the acute and long-term effects of an "NR regimen" (no-rest regimen)
      and those of a "WR regimen" (regimen with rest period within a set). Twenty-six
      male subjects were assigned to either the NR (N = 9), WR (N = 9), or control
      (CON, N = 8) groups. The NR regimen consisted of 3-5 sets of 10 repetitions at 10
      repetition maximum (RM) with an interset rest period of 1 min (lat pulldown,
      shoulder press, and bilateral knee extension). In the WR regimen, subjects
      completed the same protocol as the NR regimen, but took a 30-s rest period at the
      midpoint of each set of exercises in order to reduce exercise-induced metabolic
      stress. Acute hormonal responses to both regimens were measured followed by a 12
      wk period of resistance training. RESULTS: Measurements of blood lactate and
      serum hormone concentrations after the NR and WR regimens showed that the NR
      regimen induced strong lactate, growth hormone (GH), epinephrine (E), and
      norepinephrine (NE) responses, whereas the WR regimen did not. Both regimens
      failed to cause significant changes in testosterone. After 12 wk of resistance
      training, the NR regimen caused greater increases in 1RM (P < 0.01), maximal
      isometric strength (P < 0.05), and muscular endurance (P < 0.05) with knee
      extension than the WR regimen. The NR group showed a marked increase (P < 0.01)
      in muscle cross-sectional area, whereas the WR and CON groups did not.
      CONCLUSION: These results suggest that exercise-induced metabolic stress is
      associated with acute GH, E, and NE responses and chronic muscular adaptations
      following resistance training.

PMID- 15947721
TI  - Variability in muscle size and strength gain after unilateral resistance
      training.
AB  - PURPOSE: This study assessed variability in muscle size and strength changes in a
      large cohort of men and women after a unilateral resistance training program in
      the elbow flexors. A secondary purpose was to assess sex differences in size and
      strength changes after training. METHODS: Five hundred eighty-five subjects (342
      women, 243 men) were tested at one of eight study centers. Isometric (MVC) and
      dynamic strength (one-repetition maximum (1RM)) of the elbow flexor muscles of
      each arm and magnetic resonance imaging (MRI) of the biceps brachii (to determine
      cross-sectional area (CSA)) were assessed before and after 12 wk of progressive
      dynamic resistance training of the nondominant arm. RESULTS: Size changes ranged
      from -2 to +59% (-0.4 to +13.6 cm), 1RM strength gains ranged from 0 to +250% (0
      to +10.2 kg), and MVC changes ranged from -32 to +149% (-15.9 to +52.6 kg).
      Coefficients of variation were 0.48 and 0.51 for changes in CSA (P = 0.44), 1.07
      and 0.89 for changes in MVC (P < 0.01), and 0.55 and 0.59 for changes in CSA (P <
      0.01) in men and women, respectively. Men experienced 2.5% greater gains for CSA
      (P < 0.01) compared with women. Despite greater absolute gains in men, relative
      increases in strength measures were greater in women versus men (P < 0.05).
      CONCLUSION: Men and women exhibit wide ranges of response to resistance training,
      with some subjects showing little to no gain, and others showing profound
      changes, increasing size by over 10 cm and doubling their strength. Men had only
      a slight advantage in relative size gains compared with women, whereas women
      outpaced men considerably in relative gains in strength.

PMID- 15947722
TI  - Central and peripheral fatigue after electrostimulation-induced resistance
      exercise.
AB  - PURPOSE: To investigate central and peripheral fatigue induced by a typical
      session of electromyostimulation (EMS) of the triceps surae muscle. METHODS: A
      series of neuromuscular tests including voluntary and electrically evoked
      contractions were performed before and immediately after 13 min of EMS (75 Hz) in
      10 healthy individuals. RESULTS: Maximal voluntary contraction torque of the
      plantar flexor muscles significantly decreased (-9.4%; P < 0.001) after EMS, and
      this was accompanied by an impairment of central activation, as attested by
      twitch interpolation results (P < 0.05), whereas soleus maximal Hoffmann reflex
      and tibialis anterior coactivation did not change significantly. Contractile
      properties associated with paired stimuli and maximal M-wave amplitude for both
      soleus and medial gastrocnemius muscles (-9.4 and -38.7%, respectively) were
      significantly affected by EMS (P < 0.05), whereas postactivation potentiation did
      not change. CONCLUSION: A single bout of EMS resulted in fatigue attributable to
      both central and peripheral factors. The most obvious alteration in the function
      of the central nervous system is a decrease in the quantity of the neural drive
      to muscle from the supraspinal centers. On the other hand, neuromuscular
      propagation failure was more evident for the muscle with the higher percentage of
      Type II fibers.

PMID- 15947723
TI  - Altitude negates the benefits of aerobic training on the vascular adaptations in
      rats.
AB  - INTRODUCTION: This study questioned the effect of living and training at moderate
      altitude on aortic vasoreactivity. Considering that chronic hypoxia exposure and
      endurance training are able to generate opposite effects on the systemic vascular
      reactivity, it was hypothesized that endurance training benefits on the vascular
      function could be limited by chronic hypoxia. METHODS: Sea-level native rats were
      randomly assigned to N (living in normoxia), NT (living and training 5 d.wk for 5
      wk in normoxia), CH (living in hypoxia, 2800 m), and CHT (living and training 5
      d.wk for 5 wk in hypoxia, 2800 m) groups. Concentration response curves to
      epinephrine, norepinephrine, endothelin-1, acetylcholine, and sodium nitro
      prusside were assessed on aortic isolated rings. Left ventricular resting and
      maximal (during Tyrode's infusion) stroke volumes were evaluated by Doppler
      echocardiography and used as indexes of chronic aortic volume overload. RESULTS:
      The main finding was that favorable aortic vasoreactivity adaptations consecutive
      to sea-level training were not observed when training was conducted at altitude.
      An improvement in the endothelium-dependent vasorelaxation (maximal relaxation,
      R(max), N = 60.4 +/- 10.0 vs NT = 91.7 +/- 3.2%; P < 0.05) and a reduced
      sensitivity to ET-1 were observed in NT rats. Such an enhancement in endothelium
      dependent vasorelaxation was not found in CHT rats (R(max): 48.4 +/- 7.8%).
      Moreover, a higher sensitivity to ET-1 was reported in this group. Altitude
      induced limitation in aortic blood flow and shear stress could play a major role
      in the explanation of these specific altitude-training adaptations. CONCLUSION:
      If extrapolated to the peripheral vascular bed, our results have practical
      significance for aerobic performance as aortic vasoreactivity adaptations after
      altitude training could contribute to limit blood delivery to exercising muscles.

PMID- 15947724
TI  - Development and testing of a short physical activity recall questionnaire.
AB  - PURPOSE: To develop and test two different short telephone activity recall (STAR)
      questionnaires, one with closed-ended and the other with open-ended response
      options, that assessed overall moderate and vigorous activity in a usual week.
      METHODS: One hundred four participants completed a 3-d test-retest study, and 88
      participants completed 10-14, 24-h physical activity recalls (24PAR) and at least
      7 d of objective physical activity monitoring by Actigraph during a 28-d period.
      RESULTS: Consistency of classification from one administration to the next was
      high (65-92%), extreme inconsistencies between reports were infrequent (0-7%),
      and kappa values were between 0.50 and 0.75. Correlations between self-reports
      and criterion measures for moderate-intensity duration were between 0.30 and
      0.40. Agreement between the instruments and the 24PAR for meeting the moderate or
      vigorous recommendations was between 60 and 70%. For the 24PAR comparisons, kappa
      values tended to be higher for women than men, but were of only modest strength
      (kappa 0.40). With the 24PAR as criterion, sensitivity of the self-report
      instruments was between 50 and 90%, and specificity was between 63 and 84%. Kappa
      values comparing the instruments with the Actigraph were low (<0.20). Overall
      classification by the short instruments into meeting the recommendations was
      associated with higher levels of total 24PAR activity (P < or = 0.01) as well as
      greater steps per day and counts per minute per day from the Actigraph (P < or =
      0.08). The open-ended instrument appeared to perform better for moderate
      intensity activity, whereas the closed-ended item appeared to perform better for
      vigorous activity. CONCLUSION: The evaluated instruments had reasonable
      reliability and demonstrated an ability to capture important differences in
      overall physical activity patterns in this population, although individual
      classification errors were substantial.

PMID- 15947725
TI  - Physical activity in older, rural, Hispanic, and non-Hispanic white adults.
AB  - PURPOSE: Understanding variations in physical activity patterns is important for
      planning health interventions. This study describes age-related change in
      physical activity in 903 rural Hispanic and non-Hispanic white (NHW) adults age
      55-80. METHODS: The Physical Activity History assessed 13 categories of
      productive and recreational activity during the past year with up to four
      assessments per participant from 1987 to 1998. RESULTS: The most common
      activities were walking and home maintenance/gardening. Productive and
      recreational physical activity levels were lower in women than men (P < 0.0001),
      and within each gender group Hispanics had lower levels of both activity types
      than NHW (P values less than 0.05). In men, productive activity steadily declined
      with age in NHW and Hispanics. Recreational activity increased slightly until age
      63, then decreased after age 70. In women, productive activity initially stayed
      stable then decreased in NHW after age 63, and in Hispanics it decreased at
      younger ages before stabilizing after age 70. Recreational activity levels
      decreased steadily with age in all women, with a steeper rate of decline in NHW
      than Hispanics. In both ethnic groups, activity levels were lower in diabetics
      than nondiabetics, except for recreational activity in women where levels did not
      differ by diabetes status. CONCLUSIONS: The most common activities were similar
      to other studies of older adults, both recreational and productive activities
      contributed to total activity, and physical activity decreased in all gender
      ethnic subgroups with age. Hispanic women reported the lowest activity levels.
      Interventions to maintain or increase recreational activity may need to target
      women at an earlier age than men.

PMID- 15947726
TI  - Gender differences in frontal and sagittal plane biomechanics during drop
      landings.
AB  - PURPOSE: To determine gender differences in lower-extremity joint kinematics and
      kinetics between age- and skill-matched recreational athletes. METHODS: Inverse
      dynamic solutions estimated the lower-extremity flexion-extension and varus
      valgus kinematics and kinetics for 15 females and 15 males performing a 60-cm
      drop landing. A mixed model, repeated measures analysis of variance (gender (*)
      joint) was performed on select kinematic and kinetic variables. RESULTS: Peak hip
      and knee flexion and ankle dorsiflexion angles were greater in females in the
      sagittal plane (group effect, P < 0.02). Females exhibited greater frontal plane
      motion (group (*) joint, P = 0.02). Differences were attributed to greater peak
      knee valgus and peak ankle pronation angles (post hoc tests, P = 0.00). Females
      exhibited a greater range of motion (ROM) in the sagittal plane (group main
      effect, P = 0.02) and the frontal plane (group (*) joint, P = 0.01). Differences
      were attributed to the greater knee varus-valgus ROM, ankle dorsiflexion, and
      pronation ROM (post hoc tests). Ground reaction forces were different between
      groups (group (*) direction, P = 0.05). Females exhibited greater peak vertical
      and posterior (A/P) force than males (post hoc tests). Females exhibited
      different knee moment profiles (Group main effect, P = 0.01). These differences
      were attributed to a reduced varus moment in females (post hoc tests).
      CONCLUSION: The majority of the differences in kinematic and kinetic variables
      between male and female recreational athletes during landing were observed in the
      frontal plane not in the sagittal plane. Specifically, females generated a
      smaller internal knee varus moment at the time of peak valgus knee angulation.

PMID- 15947728
TI  - Spinal kinematics in elite oarswomen during a routine physiological "step test".
AB  - INTRODUCTION: Biomechanical measures of movement are being used increasingly to
      understand injury mechanisms and enhance performance. Frequently, rowing injuries
      are attributed to poor rowing technique. This suggests a need to understand
      technique and its influencing factors. This study aimed to quantify rowing
      technique in terms of lumbopelvic motion, force production, and work done at
      different work intensities. METHODS: An electromagnetic motion measuring device
      in conjunction with a load cell was used to determine the ergometer rowing
      kinematics of 12 elite international oarswomen during a routine step test. This
      test comprised six steps at a series of different stroke ratings starting at 18
      strokes per minute and ending at maximal-output rowing. RESULTS: As work
      intensity increased, force output increased significantly (P < 0.0001). Stroke
      length remained relatively consistent throughout the steps, although there was a
      nonsignificant shortening from 136.5 cm (+/-6.4 SD) at 18 strokes per minute to
      130.6 cm (+/-8.1) at maximal testing. Changes in kinematics were also observed,
      particularly at the catch and finish positions. There was a trend towards less
      anterior pelvic rotation occurring at the catch with an associated reduction in
      lumbar rotation and greater extensions occurring in both at the finish at the
      higher rating. Overall, rowers underutilized pelvic rotation to achieve these
      positions relying predominantly on lumbar rotation. CONCLUSION: This study
      quantified the spinal kinematics of elite rowers at different incremental work
      intensities and noted subtle but important changes to lumbopelvic and spinal
      kinematics at increasing work levels, particularly at maximal intensity. Such
      changes particularly are thought to be important with respect to the development
      of low-back pain.

PMID- 15947729
TI  - Lower-limb activity during the power serve in tennis: effects of performance
      level.
AB  - PURPOSE: The aim of the present study was to investigate the differences in lower
      limb activity during the tennis power serve between players of different
      performance levels. METHODS: Thirty-two participants distributed in three groups
      (beginner, B; intermediate, I; elite, E) performed countermovement jumps to
      measure leg power (P(max)) and 15 power serves from a force platform. Lateral,
      horizontal, and vertical forces (Fx, Fy, and Fz) were sampled simultaneously with
      EMG signals from six leg muscles. Racquet-ball impact height (I(height)) and
      maximum velocity of the ball (V(max) were measured with video analysis and radar,
      respectively. The total duration of the serve was fractioned into four phases:
      preparation (Pre), eccentric (Ecc), concentric (Con), and suspension (Sus).
      RESULTS: Pmax was similar in the three groups. The duration of Pre was longer (P
      < 0.05) in E than in B, whereas Con was shorter (P < 0.05). Vmax (169.4 +/- 11.3
      vs 107.2 +/- 6.1 kmxh, P < 0.001), I(height) (149.2 +/- 2.7 vs 142.6 +/- 4.7% of
      standing height, P < 0.05), and Fz(max) (2.12 +/- 0.36 vs 1.68 +/- 0.33 of body
      weight, P < 0.01) were higher in E than in B. I(height) was correlated (r = 0.85,
      P < 0.001) with Fz(max) in E. Peaks EMG occurred earlier (P < 0.05) in E (79 +/-
      17% of Con) than in other groups (B: 94 +/- 11% and I: 94 +/- 15%). CONCLUSION:
      The vertical forces and coordination in lower extremities during the tennis serve
      were different between players of different skill levels but with the same
      P(max). This may partly explain the differences in serve efficiency.

PMID- 15947730
TI  - The effect of loading conditions on stress in the barefooted heel pad.
AB  - PURPOSE: High internal stress is considered to be a possible cause of heel-pad
      problems. External biomechanical measurements are used to attempt to understand
      the causes of heel pain. However, internal stress cannot be measured
      experimentally. Therefore, the purpose of this study was to quantify the
      relationship between magnitude of force, time to peak force, and sole angle with
      internal stresses in the heel using a finite element model. METHODS: Computer
      tomography (CT) was used to create a nonlinear time-dependent three-dimensional
      finite element model of the heel pad. The material model was based on previously
      reported force-displacement data derived from in vitro experiments. Although it
      was not possible to compare internal calculations of stress with experimental
      data, good agreement was found for external plantar pressures and strains when
      compared with in vivo values. Internal stresses and external plantar pressures
      were then investigated for different forces, loading rates (i.e., time to peak
      force), and angles of foot inclination in the sagittal plane (i.e., sole angle).
      RESULTS: The results of the model indicate that compressive stress is localized
      in the region inferior to the calcaneal tuberosity. Peak internal compressive
      stress was greater than external plantar pressure. Increasing the loading rate
      (i.e., reducing the time to peak force) caused plantar pressure to increase to a
      greater extent than internal stress. The general levels of stress were higher
      when the heel was loaded in an inclined position (i.e., greater sole angle).
      CONCLUSION: The finite element technique provides a useful step in bridging the
      gap between external measures and internal mechanics of the heel pad. A combined
      kinematic, kinetic, and modeling approach may be required when attempting to
      identify the biomechanical source of heel pain.

PMID- 15947731
TI  - Relationship of maximum strength to weightlifting performance.
AB  - PURPOSE: The primary objective was to assess the relationship of maximum strength
      to weightlifting ability using established scaling methods. The secondary
      objective was to compare men and women weightlifters on strength and
      weightlifting ability. METHODS: Two correlational observations were carried out
      using Pearson's r. In the first observation (N = 65) the relationship of dynamic
      maximum strength (one-repetition maximum (1RM) squat) was compared with
      weightlifting ability; in the second observation (N = 16), isometric maximum
      strength (midthigh pull) was studied. Scaling methods for equating maximum
      strength and weightlifting results were used (load x (Ht), load x kg, load x lbm(
      1), allometric, and Sinclair formula) to assess the association between measures
      of maximum strength and weightlifting performance. RESULTS: Using scaled values;
      correlations between maximum strength and weightlifting results were generally
      strong in both observations (e.g., using allometric scaling for the 1RM squat vs
      the 1RM snatch: r = 0.84, N = 65). Men were stronger than women (e.g., 1RM squat,
      N = 65: men = 188.1 +/- 48.6 kg; women = 126.7 +/- 28.3 kg); differences
      generally held when scaling was applied (e.g., 1RM squat scaled with the Sinclair
      formula: men = 224.7 +/- 36.5 kg; women = 144.2 +/- 25.4 kg). CONCLUSIONS: When
      collectively considering scaling methods, maximum strength is strongly related to
      weightlifting performance independent of body mass and height differences.
      Furthermore, men are stronger than women even when body mass and height are
      obviated by scaling methods.

PMID- 15947732
TI  - Maturity status of youth football players: a noninvasive estimate.
AB  - PURPOSE: To estimate the biological maturity status of youth football players 9
      14 yr old using a noninvasive method and to compare the body size of players of
      contrasting status. METHODS: Subjects were members of youth football teams in two
      central Michigan communities. Height and weight were measured on 653 boys 8.7
      14.6 yr. Heights of biological parents of 582 boys were reported and subsequently
      adjusted for overestimation. Decimal age, height, and weight of the player and
      midparent height were used to predict mature (adult) height for the boy. Current
      height of each player was expressed as a percentage of his predicted mature
      height to provide an estimate of biological maturity status. Percentage of
      predicted mature height of each boy was expressed as a z-score to classify
      players into maturity groups. ANCOVA, controlling for age, was used to compare
      body size in contrasting maturity groups. RESULTS: Mean percentages of predicted
      mature height of the players matched those of longitudinal reference samples, but
      there was a trend for higher percentages among older players, suggesting advanced
      maturation. Overall, 405 boys were classified as on time/average in maturity
      status (69.6% [95%CI 65.7-73.3]), 154 were classified as early/advanced (25.5%
      [95%CI 23.0-30.3]), and only 23 were classified as late/delayed (3.9% [95%CI 2.6
      6.0]). The gradient for height, weight, and BMI was as follows: early > on time >
      late, and differences were greater for weight and the BMI than for height.
      CONCLUSION: Percentage of predicted mature height attained at a given age appears
      to be a reasonable indicator of maturity status. The method needs to be validated
      with other more direct indicators (skeletal age, sexual maturation) and applied
      to other samples.

PMID- 15947733
TI  - Growth of highly versus moderately trained competitive female artistic gymnasts.
AB  - PURPOSE: To investigate whether growth was adversely affected in 137 young
      competitive female artistic gymnasts involved in different training volumes.
      METHODS: This was a 2-yr prospective cohort study in which height, sitting
      height, leg length, weight, skinfolds, and pubertal status were measured in
      competitive advanced (20-27 h x wk(-1)) and intermediate (7.5-22 h x wk(-1))
      training level female gymnasts every 6-12 months. Biological parameters of the
      adolescent growth curve were estimated using the Preece-Baines growth model.
      Growth rates were estimated for both groups from the mixed-longitudinal data.
      RESULTS: Estimated ages at peak height velocity (PHV) (13-13.5 yr) and mean PHV
      (6.2-6.4 cm x yr(-1)) for the advanced- and intermediate-level gymnasts suggest
      that these gymnasts were later maturing and experienced a blunting of the growth
      spurt relative to reference values for U.S. youth. Comparison of growth
      velocities by pubertal status revealed that height velocity was lower in the
      advanced- versus the intermediate-level peripubertal gymnasts, which was due to a
      significant reduction in sitting height velocity (2.3 vs 3.1 cm x yr(-1), P. <
      0.05). No marked acceleration in height or sitting height velocity was detected
      in the advanced-level gymnasts from pre- to peripuberty. Inspection of individual
      growth rates revealed that over 35% of the pre- and peripubertal gymnasts
      experienced growth faltering (height velocity less than 4.5 cm x yr(-1)) during
      follow-up. CONCLUSION: Advanced-and intermediate-training level competitive
      female gymnasts tend to exhibit an adolescent growth spurt that is similar in
      timing and tempo to short, normal, slowly maturing girls, but the high frequency
      of growth faltering suggests that training may alter the tempo of growth and
      maturation in some, but not all, female gymnasts.

PMID- 15947734
TI  - Is leg-to-leg BIA valid for predicting minimum weight in wrestlers?
AB  - BACKGROUND: The National Collegiate Athletic Association (NCAA) and several state
      associations require prediction of minimum weight (MW) for collegiate and high
      school wrestlers. The rule requires assessment of body composition before the
      competitive season to minimize unhealthy weight-loss practices. Leg-to-leg
      bioelectrical impedance analysis (BIA) has been suggested for use with wrestlers.
      PURPOSE: To evaluate leg-to-leg BIA against a four-component (4C) criterion to
      determine whether leg-to-leg BIA predicted MW within acceptable limits for the
      sport of wrestling. METHODS: Criterion MW was calculated by the 4C equation of
      Lohman (19) using independent measurement of body density (BD) by hydrostatic
      weighing, bone mineral content (BMC) by dual x-ray absorptiometry (DXA), and
      total body water (TBW) by deuterium dilution. Subjects were 57 wrestlers (mean +/
      SD; age = 19.7 +/- 1.3 yr, height = 176.6 +/- 7.3 cm, weight = 77.7 +/- 12.4
      kg). Hydration was confirmed by the NCAA guidelines. Accuracy, precision, and
      systematic bias were examined. RESULTS: Comparable mean values (72.2 +/- 9.7 vs
      72.2 +/- 10.3 kg), a high correlation (r = 0.94), and a regression line similar
      to the line of identity were found between BIA and 4C. However, large individual
      differences and systematic bias were seen across the range of MW. BIA predicted
      MW within 3.5 kg 68% of the time and within 7.0 kg 95% of the time. MW residuals
      ranged from -10.4 kg to +6.9 kg. When using 2.0 kg as an acceptable cutoff for
      error, only 40% of the BIA values were within 2.0 kg of the criterion.
      CONCLUSION: Large individual variation was seen, and, by definition, the
      precision was poor when estimating MW for individuals. In practical terms, the
      prediction error may span multiple weight classes, thus making leg-to-leg BIA
      unacceptable for prediction of MW in this sample under the conditions of the
      study.

PMID- 15947735
TI  - Pedometer-determined walking and body composition variables in African-American
      women.
AB  - PURPOSE: This study evaluated the relationship between pedometer-determined
      physical activity and body composition variables in middle-aged, African-American
      women. METHODS: Height, weight, waist circumference, hip circumference, and
      percent body fat were measured in 69 African-American females (mean age 51.4 +/-
      5.4 yr). Subjects wore a pedometer for seven consecutive days, and average steps
      per day (i.e, walking volume) were compared with each anthropometric variable.
      Caloric intake was assessed by a 3-d diet record. The subjects were categorized
      into three different groups based on their physical activity level: <5000, 5000
      7499, and > or =7500 steps per day. A one-way analysis of variance (ANOVA) was
      performed to examine the body composition variables among the three groups.
      Partial correlation coefficients controlling for age and caloric intake were
      calculated for walking volume and body composition variables (BMI, percent body
      fat, waist and hip circumferences, and WHR). Significance was set at P < 0.05 for
      all tests. RESULTS: There were significant differences between the least active
      and most active group for age (P = 0.013), BMI (P = 0.005), percent body fat (P <
      0.001), waist circumference (P = 0.004), and hip circumference (P = 0.043). When
      a partial correlation controlling for age and caloric intake was used to compare
      steps per day with body composition variables, significant negative correlations
      still existed for each variable except WHR. These correlations were significant
      for BMI (P < 0.001), percent body fat (P < 0.001), waist circumference (P =
      0.002), and hip circumference (P = 0.017). CONCLUSIONS: Middle-aged, African
      American women who accumulate more ambulatory activity have significantly lower
      body fat percentages, BMI values, waist circumferences, and hip circumferences.

PMID- 15947736
TI  - Acute sleep responses in a normobaric hypoxic tent.
AB  - PURPOSE: Sleeping in a hypoxic environment is becoming increasingly popular among
      athletes attempting to simulate a "live high, train low" training regime. The
      purpose of this study was to investigate the acute effects (one night) of
      sleeping in a normobaric hypoxic tent (NH) (PO(2) = 110 mm Hg approximately 2500
      m) upon markers of sleep physiology and quality, compared with sleep in a normal
      ambient environment (BL) (PO(2) = 159 mm Hg approximately sea level) and sleep in
      a normobaric normoxic tent (NN) (PO(2) = 159 mm Hg). METHODS: Eight male
      recreational athletes (age 34.5 +/- 6.9 yr; stature 169.1 +/- 8.7 cm; mass 69.3
      +/- 8.2 kg; VO(2max) 56.4 +/- 8.3 mL.kg(-1).min(-1)) participated in the study
      using a randomized, double-blind crossover design. Polysomnographic studies were
      undertaken to measure sleep stages, arterial oxygen saturation (SpO(2)), heart
      rate (HR), and the Respiratory Disturbance Index (RDI). The Leeds Sleep
      Evaluation Questionnaire (LSEQ) was used to measure subjective sleep quality.
      RESULTS: NH (89.9 +/- 4.8%) resulted in a significantly lower (P < 0.05) SpO(2)
      compared with both BL (95.7 +/- 1.5%) and NN (93.5 +/- 4.0%). Heart rate was
      significantly higher (P < 0.05) in NH (51.5 +/- 7.6 beats.min(-1)) compared with
      NN (48.3 +/- 6.9 beats.min(-1)) but was similar versus BL (50.3 +/- 4.3
      beats.min(-1)). RDI (counts.h) and RDI (total counts) were lowest in BL (3.5 +/-
      2.5; 18.1 +/- 7.9) and highest in NH (36.8 +/- 42.7; 221.9 +/- 254.5). The
      difference in RDI (counts.h(-1) and total counts) between NH and BL was
      significant (P < 0.05). The LSEQ revealed that subjects' "behavior following
      waking" score was significantly (P < 0.05) lower in NH (40.9 +/- 9.2) compared
      with BL (52.3 +/- 8.3). CONCLUSION: This study presents evidence that sleep in a
      normobaric hypoxic tent at a simulated altitude of 2500 m may affect sleep
      parameters in some individuals. This type of analysis may be useful in the early
      identification of poorly responding individuals to simulated altitude
      environments.

PMID- 15947737
TI  - Constant light-induced retinal damage and the RPE65-MET450 variant: assessment of
      the NZW/LacJ mouse.
AB  - PURPOSE: In a previous constant light-induced retinal damage (CLD) quantitative
      genetics study between the albino C57BL/6J-c2J (B6al) and BALB/c mouse strains,
      we identified a very strong and highly significant quantitative trait locus (QTL)
      on distal Chr 3 that we associated with a variant of the Rpe65 gene. The B6al
      strain carries the MET450 variant of RPE65 and is resistant to CLD while the
      BALB/c strain carries the LEU450 variant and is sensitive. Since then, we have
      discovered that the NZW/LacJ (NZW) albino mouse strain is sensitive to CLD but
      carries the MET450 variant of RPE65. The purpose of this study was to determine
      if the NZW mouse disproves the hypothesis that the MET450 variant of RPE65
      protects the mouse retina against constant light-induced retinal damage. METHODS:
      F2 progeny were bred from an intercross between the NZW/LacJ and B6al mouse
      strains. After a prolonged exposure to moderate constant light, F2 mice were
      phenotyped for retinal outer nuclear layer thickness as the quantitative trait. A
      subset of 156 of the 201 F2 mice was genotyped for a set of markers spanning the
      genome, and any marker with a significant association with the quantitative trait
      was genotyped in the remaining 45 F2s. Data were analyzed for QTL by the Map
      Manager QTX software. RESULTS: No QTL was identified at distal Chr 3, although
      several QTL on Chrs 1 (two), 10, 13, 14, 16, and X were detected. One QTL on
      middle Chr 1 (LOD 5.22) mapped to the same location of a QTL (LOD 6.8) in a
      previous intense, short exposure light-induced retinal damage study conducted
      with an intercross between the 129S1/SvImJ and BALB/c strains. QTL on Chrs 1
      (distal), 10, and 14 also appeared in other retinal damage quantitative genetics
      studies. Three pairs of genes exhibited significant epistatic effects. Two of the
      pairs involved synergistic interactions between NZW and B6al alleles, and the
      third between two B6al alleles. CONCLUSIONS: If another gene besides Rpe65 was
      responsible for the QTL in the original BALB/c x B6al study, and the NZW mouse
      carried a light sensitive allele of this gene, a QTL should have been present in
      this study. Since a QTL on Chr 3 was not found, the hypothesis that RPE65-MET450
      protects the retina from constant light-induced damage is left intact. The
      explanation for the NZW mouse being sensitive to constant light while carrying
      the RPE65-MET450 variant is that other light sensitive QTL (gene alleles) negate
      the protective effect.

PMID- 15947738
TI  - Changes in the spatial expression of genes with aging in the mouse RPE/choroid.
AB  - PURPOSE: We recently used microarray and reverse transcriptase PCR (RT-PCR)
      analysis to show an upregulation of cathepsin S (CatS) and glutathione peroxidase
      3 (GPX3) in the aging mouse RPE/choroid. To evaluate the mRNA distribution and
      levels in the RPE and choroid, in situ hybridizations were performed. METHODS:
      Eye sections from 2-month-old and 24-month-old C57BL/6 mice were probed for CatS
      or GPX3 mRNA by in situ hybridization. The ratio of mRNA labeled cells to total
      cells counted per section was compared between the two age groups for the RPE and
      choroid separately. RESULTS: The CatS labeled RPE cell ratio increased
      significantly with age. The GPX3 labeled RPE cell ratio did not increase with
      age. CONCLUSIONS: The increases in mRNA levels for CatS and GPX3 found in the
      aging C57BL/6 RPE/choroid appear to represent an increase in both the numbers of
      cells expressing these messages and an increase in the level of expression in
      individual cells.

PMID- 15947739
TI  - Measurement of retinal injury in the rat after optic nerve transection: an RT-PCR
      study.
AB  - PURPOSE: In the current study, a non-histological approach, namely semi
      quantitative RT-PCR, was used to provide information on retinal ganglion cell
      (RGC) injury and survival after optic nerve transection (ONT). The levels of
      mRNAs synthesized by RGCs and glial components were initially measured at defined
      time points after ONT. Subsequently, a comparison was made between the levels of
      these mRNAs in the ONT retinas of rats treated with the neuroprotectant BDNF and
      in rats which received vehicle. METHODS: Wistar rats received an ONT in one eye,
      while the fellow eye served as a control. ONT was performed 1-2 mm from the optic
      disc without damaging the retinal blood supply. In the first experiment, rats
      were killed at 1, 3, 5, 7, and 21 days after ONT. In the second experiment, brain
      derived neurotrophic factor (BDNF; 5 microg) or vehicle was injected
      intravitreally at the same time as the ONT and animals were killed after 7 days.
      RESULTS: After ONT, mRNA levels of RGC markers (NF-L and Thy-1) decreased
      substantially, while levels of GFAP and certain trophic factors mRNAs increased
      significantly. Administration of BDNF resulted in a substantial, but not
      complete, preservation of the levels of the RGC specific mRNAs, while ONT induced
      increases in GFAP and trophic factor mRNAs were not reduced to any great extent
      by BDNF. CONCLUSIONS: The present studies show that measurement of NF-L and Thy-1
      mRNAs provides a sensitive and reliable index of RGC injury after ONT, while
      measurement of GFAP and trophic factors mRNAs provides more general information
      on the effect of the injury on the retina.

PMID- 15947741
TI  - Use of quarantine in the control of SARS in Singapore.
AB  - BACKGROUND: A total of 238 cases of the severe acute respiratory syndrome (SARS)
      occurred in Singapore between February 25 and May 11, 2003. Control relied on
      empirical methods to detect early and isolate all cases and quarantine those who
      were exposed to prevent spread in the community. METHODS: On April 28, 2003, the
      Infectious Diseases Act was amended in Parliament to strengthen the legal
      provisions for serving the Home Quarantine Order (HQO). In mounting large-scale
      quarantine operations, a framework for contact tracing, serving quarantine
      orders, surveillance, enforcement, health education, transport, and financial
      support was developed and urgently put in place. RESULTS: A total of 7863
      contacts of SARS cases were served with an HQO, giving a ratio of 38 contacts per
      case. Most of those served complied well with quarantine; 26 (0.03%) who broke
      quarantine were penalized. CONCLUSION: Singapore's experience underscored the
      importance of being prepared to respond to challenges with extraordinary
      measures. With emerging diseases, health authorities need to rethink the value of
      quarantine to reduce opportunities for spread from potential reservoirs of
      infection.

PMID- 15947742
TI  - Infection control and quality health care in the new millennium.
AB  - Health care-associated infection remains a major issue of patient safety. It
      complicates a significant proportion of patient care deliveries, adds to the
      burden of resource use, and contributes to unexpected deaths. Early infection
      control pioneers showed that surveillance and prevention programs can be
      successful and have set the scene for today's infection control activities.
      Parameters for success include those to recognize and explain health care
      associated infections and implement interventions to decrease infection rates and
      limit antimicrobial resistance spread. Current major challenges facing infection
      control programs are reviewed with an emphasis on recent trends in health care
      delivery systems, together with some vision on future activities and interactions
      toward such changes. Benchmarking of infection rates is considered inevitable,
      and, thus, surveillance strategies, adapted to changing health care systems,
      should improve and emphasize intervention and standardization. Major challenges
      for the future include antimicrobial use and control of resistances, new
      materials, emerging pathogens, infection control issues related to transgenic
      therapy, massive and complete immunosuppression and xenotransplantation, prion
      diseases, use of fully computerized patient record and data-mining-derived
      epidemiology, development of evidence-based recommendations for infection control
      and prevention, addressing cost constraints and newly apparent health care system
      trends, and health care worker behavior modification.

PMID- 15947743
TI  - Health care-associated infections in the neonatal intensive care unit.
AB  - Neonates represent a unique and highly vulnerable patient population. Advances in
      medical technology that have occurred over the last few decades have improved the
      survival and quality of life for neonates, particularly those infants born with
      extreme prematurity or with congenital defects. Although immunologic immaturity
      and altered cutaneous barriers play some role in the vulnerability of neonates to
      nosocomial infections, clearly, therapeutic interventions that have proven to be
      lifesaving for these fragile infants also appear to be associated with the
      majority of infectious complications resulting in neonatal morbidity and
      mortality. Rates of infections in neonatal intensive care units (NICUs) have
      varied from 6% to 40% of neonatal patients, with the highest rates in those
      facilities having larger proportions of very low-birth-weight infants
      (birthweight < or =1000 grams) or neonates requiring surgery. Efforts to protect
      the vulnerable NICU infants include the following: (1) optimal infection control
      practices, especially good hand hygiene and good nursery design; (2) prudent use
      of invasive interventions with particular attention to early removal of invasive
      devices after they are no longer essential; and (3) judicious use of
      antimicrobial agents, with an emphasis on targeted (narrow spectrum) rather than
      broad-spectrum antibiotics and appropriate indications (proven or suspected
      bacterial infections).

PMID- 15947744
TI  - Infectious disease in pediatric out-of-home child care.
AB  - Provision of some form of child care outside of the home is certainly not a new
      phenomenon. In the past, most out-of-home care was provided by a relative, a
      friend, or someone who had a specific relationship with the family of the child.
      The frequency of utilization of child care centers for out-of-home care and the
      different formats of out-of-home care services has increased within recent
      decades and will vary by geographic location. Also, there is an increased
      utilization of temporary child care such as "mother's day out" or baby-sitting
      services provided at churches, grocery stores, and other places. Child care
      centers represent special risks for transmission of infectious agents because
      young children exhibit high susceptibility to many community-acquired viruses and
      bacteria; they lack developmental understanding required for good hygiene; and
      they frequently receive antibiotics (appropriately and inappropriately).
      Infections acquired in child care centers can significantly impact the health of
      the children who acquire the infection and also result in significant economic
      impacts on the child's family, particularly if 1 or more of the parents has to
      lose time from work. In the United States, it is estimated that families who have
      children in child care lose 13 days of work per year for all types of infections.
      Interventions that have proven valuable for reducing infections within child care
      centers include the following: (1) formal written policies for infection control
      within the child care center, (2) formal education of child care center staff
      concerning infection control practices (needs to be repeated; preferably on a
      recurring basis), (3) good hand hygiene by both staff and children, (4)
      appropriate cleaning of contaminated surfaces, (5) separation of food preparation
      and diaper changing, (6) exclusion of certain ill children, (7) cohorting ill
      children when exclusion is not possible, (8) ensuring adequate age-appropriate
      immunization of child care attendees and staff, and (9) optimal ratios of
      children to staff.

PMID- 15947745
TI  - Surveillance, prevention, and control of legionellosis in a tropical city-state.
AB  - Legionellosis is endemic in Singapore, with sporadic cases reported throughout
      the year. The absence of outbreak could be due to the low prevalence of the
      highly pathogenic Pontiac subtype of Legionella pneumophila in the urban
      environment. Mandatory maintenance of cooling towers and water fountains has been
      put in place, and the effectiveness of legislation in minimizing the occurrence
      and risk of outbreak of legionellosis is being evaluated.

PMID- 15947746
TI  - Risk factors for prediction of surgical site infections in "clean surgery".
AB  - BACKGROUND: The aim of this study was to determine the risk factors of surgical
      site infections (SSI) in clean surgery and to identify high- and low-risk
      patients from whom efficacy of the antibiotic prophylaxis was analyzed. METHODS:
      From June 1982 to September 1996, a database was established from 3 prospective
      multicenter randomized studies, containing information of 5798 patients who
      underwent abdominal noncolorectal surgery. Multivariate analysis was performed
      using nonconditional logistic regression expressed as an odds ratio (OR).
      RESULTS: A total of 2374 patients underwent a clean surgery. An antibiotic
      prophylaxis was administered to 1943 patients (81.8%). A multivariate analysis
      was performed including only preoperative factors and disclosed 3 independent
      factors: cirrhosis (OR, 2.8; 95% CI: 1.6-12.8), other disease (OR, 2.7; 95% CI:
      1.3-5.8), and preoperative urinary catheter (OR, 2.1; 95% CI: 1.1-4.6). A risk
      score for SSI was constructed: -4.9 + (1.5 x cirrhosis++) + (other disease++) +
      (0.8 x preoperative urinary catheter++) (++ = 0 if absent or 1 if present). The
      study included 1 group of patients having no risk factors for SSI with a score
      below -4.5 (S1R-) and 1 group of patients having 1 or more risk factors for SSI
      with a score over -4.5 (S1R+). Antibiotic prophylaxis did not reduce the
      infectious complication rate in the S1R- group, whereas, in the S1R+ group, it
      reduced significantly the rate of SSI and of parietal infectious complications by
      58% and 69%, respectively. CONCLUSIONS: Antibiotic prophylaxis in clean abdominal
      surgery was effective in high-risk patients. Urinary catheter must be avoided.

PMID- 15947747
TI  - Public attitudes and opinions toward physicians and dentists infected with
      bloodborne viruses: results of a national survey.
AB  - BACKGROUND: There has been no recent assessment of public attitudes and opinions
      concerning risk of bloodborne virus transmission during health care. METHODS:
      Seven items in the 2000 annual Healthstyles survey were used to assess current
      attitudes and opinions about health care providers infected with human
      immunodeficiency virus (HIV) and the risk of bloodborne virus transmission during
      health care in a sample of approximately 3000 US households. RESULTS: Of the 2353
      respondents, 89% agreed that they want to know whether their doctor or dentist is
      infected with HIV; 82% agreed that disclosure of HBV or HCV infection in a
      provider should be mandatory. However, 47% did not believe that HIV-infected
      doctors were more likely to infect patients than doctors infected with HBV or
      HCV. Opinions were divided on whether HIV-infected providers should be able to
      care for patients as long as they use good infection control: only 38% thought
      that infected providers should be allowed to provide patient care. CONCLUSIONS:
      These findings suggest that improved public education and risk communication on
      health care-associated bloodborne infections is needed.

PMID- 15947748
TI  - Short time to positivity in blood culture with clustered gram-positive cocci on
      direct smear examination is highly predictive of Staphylococcus aureus.

PMID- 15947749
TI  - Sporicidal activity in liquid chemical products to sterilize or high-level
      disinfect medical and dental instruments.
AB  - BACKGROUND: Various liquid chemical products are commercially available in Mexico
      under sporicidal label claims. Frequently, information provided on their labels
      conflicts with published data on active ingredients, use concentrations, or
      exposure times. OBJECTIVE: To evaluate sporicidal activity in 8 chemical products
      sold for the sterilization or high-level disinfection of medical and dental
      instruments. METHODS: Bacillus atrophaeus ATCC 9372 spores were suspended (10 6
      spores in 50 mL) in each of 4 glutaraldehyde solutions: a super oxidized
      solution, a hydrogen peroxide formulation, a quaternary ammonium compound, and an
      ortho -phthalaldehyde solution. After up to a 10-hour exposure, the solutions
      were passed through 0.22-mum filters, which were then rinsed with 1% sodium
      bisulfite, washed, and incubated on tryptic soy agar for 5 days at 37 degrees C.
      RESULTS: At the use concentrations stipulated on their labels, only 2 of 6
      products registered as sterilants showed sporicidal activity when challenged with
      6 log 10 : a 2% glutaraldehyde in 10 hours and the hydrogen peroxide solution in
      6 hours. Of 2 products registered as high-level disinfectants, only the ortho 
      phthalaldehyde showed noticeable sporicidal activity after 10-hour exposure.
      CONCLUSION: The results show that some chemical products, commercially available
      in Mexico as "Liquid Chemical Sterilants/High-Level Disinfectants" cannot be used
      reliably to process instruments between patients.

PMID- 15947750
TI  - A descriptive review of malpractice claims for health care-acquired infections in
      Philadelphia.
AB  - BACKGROUND: Philadelphia's rate of malpractice filings per population is just
      over double the national median. Plaintiffs prevail in 44% of verdicts in
      Philadelphia compared with 20% for all US jury verdicts, with 24% of awarded
      verdicts in excess of $1 million. OBJECTIVE: To determine patient and procedure
      demographic data for malpractice claims involving health care-acquired infections
      (HAIs) in Philadelphia. METHODS: Risk managers representing 60 acute care
      hospitals, members of Pennsylvania Trial Lawyers Association, and a random sample
      of 560 lawyers representing plaintiff and defense cases obtained from the
      Philadelphia Court of Common Pleas database (1996-2002) were surveyed. The survey
      included the following: number of HAI cases by specialty, body site, isolate, and
      outcome. RESULTS: Overall response rate was 25% (n = 154 cases). The highest
      numbers of cases were in the specialties of orthopedics (69), general surgery
      (20), and cardiothoracic (20). Sites infected most often were as follows: knees
      (26), back (26), sternum (18), and harvest site (10). Methicillin-resistant
      Staphylococcus aureus (MRSA) was responsible for 45 of cases, S epidermidis for
      27, methicillin-susceptible S aureus (MSSA) for 14, and Pseudomonas for 16.
      Twenty-seven of the cases were withdrawn, 27 settled, 11 pending, 9 plaintiff
      verdict, and 5 defense verdict. CONCLUSIONS: Although 72% of HAI malpractice
      cases in Philadelphia were either withdrawn or settled, when brought to trial,
      the plaintiff was more likely to succeed with a verdict. Our findings also
      suggest that the most frequent type of infection (class I-surgical site) and
      isolate (MRSA) are more likely to be seen as preventable HAIs because of National
      Nosocomial Infection Surveillance data showing lower infection rates for this
      class of surgery and therefore seen as easier for the plaintiff to show that the
      defendant failed to adhere to the standard of care for infection control.

PMID- 15947751
TI  - Prevalence rate of active tuberculosis from chest radiography among Thai hospital
      personnel: a summary.

PMID- 15947762
TI  - The use of hand-carried ultrasound in the hospital setting--a cost-effective
      analysis.
AB  - OBJECTIVES: We sought to assess the accuracy of hand-carried ultrasound (HCU) in
      the prediction of a normal study, and its cost-effectiveness in reducing the
      number of standard departmental echocardiograms (SDE) performed on hospital
      inpatients. METHODS: The setting was a district general hospital. Participants
      were 157 consecutive inpatients, mean age 68 (range: 18-97) years, 95 men (61%),
      referred for SDE. HCU was performed at the bedside as part of the clinical
      assessment. SDE was performed routinely. Main outcome measures were: (1)
      assessment of the accuracy of HCU in detection of a normal or abnormal study as
      determined by SDE; and (2) a cost-effectiveness analysis. RESULTS: Indications
      for echocardiography were: left ventricular (LV) function assessment, n = 101
      (64.3%); valvular abnormalities, n = 11 (7%); arrhythmia, n = 4 (2.6%);
      miscellaneous, n = 10 (6.4%); and no reason stated, 31 (19.7%). The sensitivity,
      specificity, and positive and negative predictive values of HCU predicting a
      completely normal scan were 74%, 96%, 94%, and 81%, respectively, and of
      predicting normal LV function in requests specific for LV function assessment
      were 81%, 100%, 100%, and 77%, respectively. If either all inpatients or those
      with requests for LV function assessment underwent HCU initially, and only those
      with abnormal scans underwent further SDE, there would be a 29% and 22% reduction
      in departmental workload and a cost saving of pound sterling 23,000 and pound
      sterling 30,000, respectively. CONCLUSION: HCU is an accurate method of
      identifying patients with normal hearts as determined by SDE. Its routine use is
      cost-effective and can significantly reduce the number of SDE that need be
      performed.

PMID- 15947763
TI  - An initial application of transesophageal Doppler echocardiography in
      experimental small animal models.
AB  - This study examined whether an intracardiac echocardiography catheter could be
      used for transesophageal echocardiography (TEE) examinations in normal rats, and
      intraoperative TEE in small animal models of disease. The study used 30 Sprague
      Dawley normal rats, 10 rats undergoing coronary artery ligation, and 10 rats with
      experimentally induced mitral regurgitation. The rats were anesthetized with
      isoflurane and intubated. An intracardiac echocardiographic catheter was inserted
      into the esophagus. M-mode, 2-dimensional, and Doppler studies were performed in
      multiple views. TEE probe insertions were successful in all animals.
      Intraoperative TEE was safely performed in the rat models of myocardial
      infarction or mitral regurgitation. Mitral regurgitation was well assessed using
      color Doppler and pulmonary venous flow. This study demonstrates that TEE
      (including intraoperative TEE) can be safely performed in rats using an
      intracardiac echocardiographic catheter. It provides a new approach to the
      assessment of cardiac function and valvular regurgitation in small animals.

PMID- 15947764
TI  - Assessment of mitral annular velocities by Doppler tissue imaging in predicting
      left ventricular thrombus formation after first anterior acute myocardial
      infarction.
AB  - The aim of this study was to determine whether early assessment of left
      ventricular (LV) systolic and diastolic functions by pulsed wave Doppler tissue
      imaging predicts LV thrombus formation after acute anterior myocardial
      infarction. Echocardiography was performed in 87 consecutive patients with first
      acute anterior myocardial infarction within 24 hours after arrival to the
      coronary care department. Mitral inflow velocities and early diastolic (Em), late
      diastolic (Am), and peak systolic (SM) mitral annular velocities were measured.
      Em/Am and the ratio of early diastolic mitral inflow velocity to Em (E/Em), which
      is a reasonably good index for predicting elevated LV filling pressure, were
      calculated. To detect LV thrombus, 2-dimensional echocardiography was repeated on
      days 3, 7, 15, and 30. Patients were divided into two groups according to LV
      thrombus formation: group 1 (n = 29; aged 59 +/- 11 years; 4 women) with
      thrombus; and group 2 (n = 58; aged 57 +/- 9 years; 6 women) without thrombus.
      Members of group 1 had significantly lower Em, a lower SM, a lower peak systolic
      mitral annular velocity, and a lower Em/Am than those in group 2 (6.4 +/- 2.0
      cm/s vs 8.9 +/- 2.7 cm/s, P < .001; 7.3 +/- 1.6 cm/s vs 8.6 +/- 1.7 cm/s, P =
      .001; 0.65 +/- 0.25 cm/s vs 0.89 +/- 0.27 cm/s, P < .001, respectively). The E/Em
      was significantly higher in group 1 than in group 2 (12.5 +/- 5.0 vs 7.2 +/- 2.8,
      P < .001). The sensitivity of an E/Em ratio greater than 9 in predicting LV
      thrombus formation was 69%, the specificity 79%, the positive predictive value
      63%, and the negative predictive value 84%. Mitral annular velocities derived by
      pulsed wave Doppler tissue imaging are simple to obtain even in technically
      suboptimal studies, and can be used for predicting LV thrombus formation after
      myocardial infarction.

PMID- 15947765
TI  - Ultrasonic tissue characterization predicts left ventricular remodeling in
      patients with acute anterior myocardial infarction after primary coronary
      angioplasty.
AB  - OBJECTIVES: The aim of this study was to assess the role of cyclic variation (CV)
      of myocardial integrated backscatter (IBS) in the prediction of left ventricular
      (LV) remodeling in patients with anterior acute myocardial infarction (AMI) after
      primary coronary angioplasty. BACKGROUND: Some studies have shown that the CV of
      myocardial IBS predicts myocardial viability for patients with AMI. METHODS: We
      recorded short-axis IBS images within 24 hours of angioplasty in 80 patients with
      anterior AMI. Two parameters were measured: the magnitude of CV and the
      normalized time delay (NTD). The increase in LV end-diastolic volume (LVEDV) at 4
      weeks (DeltaLVEDV) was defined as LV remodeling (>20% increase from baseline).
      RESULTS: Patients were divided into two groups according to LV remodeling status:
      the remodeling group (n = 41) and the nonremodeling group (n = 39). There was a
      significant difference in the magnitude of CV between the two groups (5.11 +/-
      1.47 vs 5.96 +/- 189 dB, P < .05), and the NTD was significantly different in the
      two groups (1.57 +/- 0.31 vs 1.23 +/- 0.32, P < .0001). The correlation between
      the magnitude of CV and DeltaLVEDV was significant but weak (r = -0.338, P <
      .01). There was significant correlation between NTD and DeltaLVEDV (r = 0.443, P
      < .0001). Using NTD greater than 1.35 as the optimal cutoff, the sensitivity,
      specificity, and positive and negative predictive values to predict LV remodeling
      were 82%, 86%, 87%, and 80%, respectively. CONCLUSIONS: Myocardial IBS,
      especially NTD, is useful for predicting LV remodeling in patients with AMI after
      primary coronary angioplasty.

PMID- 15947766
TI  - Prognosis of patients with good exercise capacity and mildly abnormal exercise
      echocardiography results: identification of an at-risk subgroup.
AB  - BACKGROUND: Patients with good exercise capacity and mildly abnormal exercise
      echocardiography results have a favorable overall prognosis. OBJECTIVE: We sought
      to define subgroups that might be at higher risk. METHODS: We examined outcomes
      of 868 patients (women, > or = 5 metabolic equivalents; men, > or = 7 metabolic
      equivalents) with mild rest- or exercise-induced wall-motion abnormalities and
      evaluated potential predictors of time to cardiac death or nonfatal myocardial
      infarction (MI). RESULTS: Mean age was 64 +/- 10 years; 477 patients (55%) were
      men. Mean follow-up was 3.1 +/- 1.5 years; cardiac event rate was 1.2% per person
      year. A history of MI was the only significant predictor (risk ratio, 3.9; 95%
      confidence interval, 1.9-7.8; P = .0001), with 1-, 3-, and 5-year event-free
      survival of 98.5% +/- 1.1%, 92.6% +/- 2.6%, and 83.3% +/- 5.1%, respectively
      (event rate, 3.4%). CONCLUSIONS: Patients with a history of MI have a higher
      annual cardiac event rate and may benefit from reevaluation, whereas no history
      of MI connotes a favorable prognosis.

PMID- 15947768
TI  - Incidence of cerebral embolism after cardioversion of atrial fibrillation: a
      prospective study with transesophageal echocardiography and cerebral magnetic
      resonance imaging.
AB  - BACKGROUND: After cardioversion of atrial fibrillation the risk for cerebral
      embolism is increased. There is little knowledge about the incidence of cerebral
      embolism for patients with transesophageal echocardiography (TEE)-guided
      cardioversion under oral anticoagulation. METHODS: Consecutive patients with
      atrial fibrillation and TEE-guided cardioversion were included in the study. We
      performed serial TEE studies, Holter electrocardiography, cranial magnetic
      resonance imaging, and clinical examinations during a period of 4 weeks before
      and after cardioversion. Oral anticoagulation was continued or initiated in all
      patients. RESULTS: During the observation period 6 of 127 (4.7%) patients had new
      embolic lesions after cardioversion documented on cerebral magnetic resonance
      imaging. Patients with an event were significantly older (P = .04) and had a
      larger left atrium (P = .04) than patients without event. CONCLUSION: Patients
      with atrial fibrillation and oral anticoagulation have a low rate of clinical
      apparent cerebral embolism after TEE and anticoagulation-guided cardioversion.
      The rate of silent cerebral embolism is almost 5%. Age and left atrial size are
      predictors for an event.

PMID- 15947769
TI  - Transesophageal echocardiography in comparison with magnetic resonance imaging in
      the diagnosis of pulmonary vein stenosis after radiofrequency ablation therapy.
AB  - OBJECTIVE: Doppler-derived flow velocity measured by transesophageal
      echocardiography (TEE) may overestimate pulmonary vein stenosis. We hypothesized
      that combining peak velocity with a stenotic flow pattern improves diagnosis
      compared with magnetic resonance imaging (MRI). METHODS: TEE and MRI were
      performed in 44 patients 19 +/- 11 months after radiofrequency catheter ablation.
      Pulmonary vein stenosis was defined by a peak velocity of 110 cm/s or more plus a
      stenotic flow pattern (turbulence and reduced flow variation) on TEE and a lumen
      reduction of more than 50% on MRI. RESULTS: In all, 175 pulmonary veins were
      studied. MRI showed 7 cases of pulmonary vein stenosis that were correctly
      identified by TEE. In addition, TEE criteria for pulmonary vein stenosis were met
      in 4 pulmonary veins that did not show obstruction on MRI. In all, 5 pulmonary
      veins with normal appearance on MRI had peak velocity of 110 cm/s or more with
      normal flow pattern. CONCLUSIONS: TEE Doppler measurements can be reliably used
      to detect or exclude significant pulmonary vein stenosis if the diagnosis is
      restricted to a combination of elevated peak velocity (> or = 110 cm/s) with
      turbulence and little flow variation.

PMID- 15947770
TI  - Echocardiographic features and complications of the modified Norwood operation
      using the right ventricle to pulmonary artery conduit.

PMID- 15947771
TI  - Contribution of Doppler tissue imaging and myocardial performance index to
      assessment of left ventricular function in patients with Duchenne's muscular
      dystrophy.
AB  - Doppler tissue velocities (DTV) are abnormal in a variety of cardiac conditions
      when standard measures of ventricular function are normal. Detection of left
      ventricular dysfunction in Duchenne's muscular dystrophy (DMD) has relied on 2
      dimensional imaging yet often these images are suboptimal. This study was
      undertaken to determine if DTV and the myocardial performance index (MPI) could
      provide additional diagnostic information in DMD. We determined in 31 patients
      and 13 age-matched control subjects the prevalence of both abnormal DTV of the
      mitral annulus and abnormal MPI. Mean values for early diastolic DTV were
      significantly lower for patients compared with control subjects (P < .001) and
      were abnormally low in 86% of patients. The MPI was abnormal in 79% of patients.
      All but one patient with DMD had either abnormal DTV or abnormal MPI yet 19% had
      normal fractional shortening. DTV and MPI are important additions to the
      echocardiographic evaluation of patients with DMD.

PMID- 15947772
TI  - The peak to mean pressure decrease ratio: a new method of assessing aortic
      stenosis.
AB  - BACKGROUND: The ratio of peak to mean pressure decrease is a new measure of
      transaortic continuous waveform shape that could be useful for grading aortic
      stenosis. METHODS: We retrospectively analyzed echocardiograms in 163 patients
      with all grades of aortic stenosis as assessed by the continuity equation.
      RESULTS: The peak to mean pressure decrease ratio was 1.75 (0.14) in mild
      stenosis, 1.66 (0.13) in moderate stenosis, 1.56 (0.10) in severe stenosis, and
      1.57 (0.07) in severe aortic stenosis with left ventricular ejection fraction
      less than 40%. Receiver operating characteristic curve analysis showed that a
      threshold of less than 1.50 gave a specificity of 94% against continuity area
      whereas a ratio less than 1.75 gave a sensitivity of 96%. CONCLUSION: The peak to
      mean pressure decrease ratio is a simple and quick cue to the likelihood of
      severe aortic stenosis in patients with low left ventricular ejection fraction
      when transaortic pressure decreases appear only moderate.

PMID- 15947773
TI  - Transthoracic Doppler echocardiography as a noninvasive tool to assess coronary
      artery stenoses--a comparison with quantitative coronary angiography.
AB  - We prospectively tested the diagnostic accuracy of Doppler transthoracic
      echocardiography in detection of coronary artery stenoses throughout the main
      coronary arterial tree. In all, 84 patients referred for diagnostic quantitative
      coronary angiography were studied. Coronary artery stenosis was identified with
      color Doppler as local spot of turbulence, and local flow velocity was measured
      using pulsed wave Doppler. Angiography showed significant stenoses (diameter
      reduction > 50%) in 33 patients. An abnormal maximal-to-prestenotic blood flow
      velocity ratio greater than 2.0 in subtotal stenoses, or the detection of
      collateral blood flow in the absence of normal antegrade flow in the case of
      total occlusion (N = 6), resulted in overall sensitivity of 82% and specificity
      of 92%. The sensitivity and specificity were, respectively, 73% and 92% for left
      anterior descending coronary artery, 63% and 96% for right coronary artery, and
      38% and 99% for left circumflex coronary artery stenoses. Transthoracic
      echocardiography is a promising noninvasive technique to diagnose significant
      coronary artery stenoses.

PMID- 15947774
TI  - Demonstration of recanalized left coronary artery after thrombolysis by
      transthoracic echocardiography.
AB  - BACKGROUND: Demonstration of recanalized coronary artery is mostly done by
      angiographic techniques. Early bedside demonstration of reperfusion after
      thrombolysis by transthoracic echocardiography (TTE) has important implications
      in the subsequent risk stratification and timing of coronary interventions.
      METHODS: In this study, 12 patients with acute anterior myocardial infarction who
      received thrombolytic therapy were studied. Echocardiographic Doppler evaluation
      of left main coronary artery, proximal left anterior descending coronary artery
      (LAD), and proximal left circumflex coronary artery were studied before, during,
      and after thrombolytic therapy. Coronary flow in these arterial segments was
      assessed both by color flow and velocity measurements. These results were
      compared with coronary angiographic studies performed within 30 minutes to 48
      hours of thrombolysis. RESULTS: Blood flow in left main coronary artery, LAD, and
      left circumflex coronary artery could be assessed in 9 patients. There was no
      demonstrable flow in LAD in 6 patients before thrombolysis. In 7 patients flow
      could be demonstrated in LAD after thrombolysis within 15 minutes to 6 hours. The
      peak flow velocity in LAD at a localized area of turbulence postthrombolysis
      varied from 1.8 to 4.5 m/s. One patient showed mosaic color flow in left main
      coronary artery with a peak velocity of 1.9 m/s before thrombolysis that improved
      to a laminar flow with a peak velocity of 1.0 m/s after thrombolysis. Two
      patients showed normal flow in proximal LAD, but no flow in mid-LAD. Two patients
      did not show any flow in LAD even after 12 hours of thrombolysis. There was good
      correlation of site of critical narrowing in LAD by TTE with coronary angiography
      in 6 patients. In 3 patients absent flow in mid-LAD by TTE correlated with total
      occlusion of either proximal (one patient) or mid-LAD (two patients).
      CONCLUSIONS: Demonstration of recanalized infarct-related left coronary artery
      soon after thrombolytic therapy is feasible. Locating the actual site of critical
      narrowing at bedside by TTE has important implications in the subsequent
      treatment of patients with acute anterior wall myocardial infarction.

PMID- 15947775
TI  - Isolated left ventricular noncompaction of the myocardium as a cause of embolic
      superior mesenteric artery occlusion.
AB  - Isolated noncompaction of the left ventricular (LV) myocardium is a rare
      congenital disorder resulting from an arrest of the compaction process of the
      myocardial trabeculae during normal embryogenesis. It is characterized by the
      presence of prominent LV myocardial trabeculations and deep intertrabecular
      recesses that are in continuity with the LV cavity. The most common clinical
      presentation includes progressive LV dysfunction, life-threatening
      tachyarrhythmias, and the risk for severe cardioembolic events. We describe a
      case where isolated noncompaction of the LV myocardium was diagnosed after an
      embolic occlusion of the superior mesenteric artery in a 40-year-old Caucasian
      woman.

PMID- 15947776
TI  - Neonatal pulmonary artery thrombosis: echocardiographic characteristics and
      possible contributing factors.

PMID- 15947777
TI  - Three unusual myxomas originating from the left atrial appendage: a case report.
AB  - Most left atrial appendage masses have been reported to be thrombus, particularly
      in the presence of atrial fibrillation. The presence of any mass other than
      thrombus is extremely rare in the left atrial appendage. This report presents the
      rare case of a 70-year-old woman presenting with paroxysmal atrial fibrillation
      and syncope who was given the diagnosis of having 3 myxomas originating from the
      left atrial appendage. The diagnosis was established by the help of
      transesophageal echocardiography and confirmed by histologic examination after
      operation. The advantage of transesophageal echocardiography in this case and for
      patients with atrial fibrillation is emphasized.

PMID- 15947778
TI  - Pericarditis constrictiva and high-degree atrioventricular block as a first
      manifestation of a cardiac B-cell lymphoma.
AB  - Primary cardiac lymphoma is an extremely rare extranodal non-Hodgkin's lymphoma,
      exclusively located in the heart and/or the pericardium with no evidence of
      extracardiac dissemination. In this report, we describe a cardiac B-cell lymphoma
      arising in a 70-year-old woman who presented to the hospital with heart failure
      symptoms and a high-degree atrioventricular block of unknown origin.
      Echocardiography revealed a massive infiltrative thickening of the atrial septum,
      the aortic root, and the pericardium. Pulsed wave and Doppler tissue findings
      were highly suggestive for pericarditis constrictiva. Positron emission
      tomography showed unusually strong metabolic activity in the atrial septum, both
      atria, and the entire pericardium. Suggested malignoma was confirmed by the
      pericardial biopsy specimens, which revealed a high-grade diffuse CD20+ B-cell
      lymphoma.

PMID- 15947779
TI  - Right-sided Myxomas.
AB  - Primary tumors of the heart are rare with an incidence of 0.0017% to 0.19% in
      unselected patients at autopsy. Of those tumors, cardiac myxomas are the most
      commonly seen and account for about 50% of primary cardiac tumors. About 75% to
      85% of myxomas originate in the left atrium, 15% to 20% in the right atrium, and
      only rare cases have been reported of myxomas originating in the left and right
      ventricles (5%). We present 3 cases in which right-sided myxomas were diagnosed
      echocardiographically and review the literature on primary cardiac myxomas.

PMID- 15947782
TI  - Crystal structure of a polyphosphate kinase and its implications for
      polyphosphate synthesis.
AB  - Polyphosphate (polyP), a linear polymer of hundreds of orthophosphate residues,
      exists in all tested cells in nature, from pathogenic bacteria to mammals. In
      bacteria, polyP has a crucial role in stress responses and stationary-phase
      survival. Polyphosphate kinase (PPK) is the principal enzyme that catalyses the
      synthesis of polyP in bacteria. It has been shown that PPK is required for
      bacterial motility, biofilm formation and the production of virulence factors.
      PPK inhibitors may thus provide a unique therapeutic opportunity against
      antibiotic-resistant pathogens. Here, we report crystal structures of full-length
      Escherichia coli PPK and its complex with AMPPNP (beta-gamma-imidoadenosine 5
      phosphate). PPK forms an interlocked dimer, with each 80 kDa monomer containing
      four structural domains. The PPK active site is located in a tunnel, which
      contains a unique ATP-binding pocket and may accommodate the translocation of
      synthesized polyP. The PPK structure has laid the foundation for understanding
      the initiation of polyP synthesis by PPK.

PMID- 15947783
TI  - A SNF2-like protein facilitates dynamic control of DNA methylation.
AB  - DRD1 is a SNF2-like protein previously identified in a screen for mutants
      defective in RNA-directed DNA methylation of a seed promoter in Arabidopsis.
      Although the initial study established a role for DRD1 in RNA-directed DNA
      methylation, it did not address whether DRD1 is needed for de novo or maintenance
      methylation, or whether it is required for methylation of other target sequences.
      We show here that DRD1 is essential for RNA-directed de novo methylation and acts
      on different target promoters. In addition, an unanticipated role for DRD1 in
      erasure of CG methylation was shown when investigating maintenance methylation
      after segregating away the silencing trigger. DRD1 is unique among known SNF2
      like proteins in facilitating not only de novo methylation of target sequences in
      response to RNA signals, but also loss of methylation when the silencing inducer
      is withdrawn. The opposing roles of DRD1 could contribute to the dynamic
      regulation of DNA methylation.

PMID- 15947784
TI  - Binding of EMSY to HP1beta: implications for recruitment of HP1beta and BS69.
AB  - EMSY is a large nuclear protein that binds to the transactivation domain of
      BRCA2. EMSY contains an approximately 100-residue segment at the amino terminus
      called the ENT (EMSY N-terminal) domain. Plant proteins containing ENT domains
      also contain members of the royal family of chromatin-remodelling domains. It has
      been proposed that EMSY may have a role in chromatin-related processes. This is
      supported by the observation that a number of chromatin-regulator proteins,
      including HP1beta and BS69, bind directly to EMSY by means of a conserved motif
      adjacent to the ENT domain. Here, we report the crystal structure of residues 1
      108 of EMSY at 2.0 A resolution. The structure contains both the ENT domain and
      the HP1beta/BS69-binding motif. This binding motif forms an extended peptide-like
      conformation that adopts distinct orientations in each subunit of the dimer.
      Biophysical and nuclear magnetic resonance analyses show that the main complex
      formed by EMSY and the chromoshadow domain of HP1 (HP1-CSD) consists of one EMSY
      dimer sandwiched between two HP1-CSD dimers. The HP1beta-binding motif is
      necessary and sufficient for EMSY to bind to the chromoshadow domain of HP1beta.

PMID- 15947786
TI  - NF-kappaB meets ROS: an 'iron-ic' encounter.

PMID- 15947785
TI  - Impairing the bioenergetic status and the biogenesis of mitochondria triggers
      mitophagy in yeast.
AB  - Autophagy, a highly regulated programme found in almost all eukaryotes, is mainly
      viewed as a catabolic process that degrades nonessential cellular components into
      molecular building blocks, subsequently available for biosynthesis at a lesser
      expense than de novo synthesis. Autophagy is largely known to be regulated by
      nutritional conditions. Here we show that, in yeast cells grown under nonstarving
      conditions, autophagy can be induced by mitochondrial dysfunction. Electron
      micrographs and biochemical studies show that an autophagic activity can result
      from impairing the mitochondrial electrochemical transmembrane potential.
      Furthermore, mitochondrial damage-induced autophagy results in the preferential
      degradation of impaired mitochondria (mitophagy), before leading to cell death.
      Mitophagy appears to rely on classical macroautophagy machinery while being
      independent of cellular ATP collapse. These results suggest that in this case,
      autophagy can be envisioned either as a process of mitochondrial quality control,
      or as an ultimate cellular response triggered when cells are overwhelmed with
      damaged mitochondria.

PMID- 15947787
TI  - RAIDD is required for apoptosis of PC12 cells and sympathetic neurons induced by
      trophic factor withdrawal.
AB  - Caspase 2 has been implicated in trophic deprivation-induced neuronal death. We
      have shown that overexpression of the caspase 2-binding protein RAIDD induces
      neuronal apoptosis, acting synergistically with trophic deprivation. Currently,
      we examine the role of endogenous RAIDD in apoptosis of PC12 cells and
      sympathetic neurons. Expression of a truncated caspase recruitment domain-only
      form of caspase 2, which presumably disrupts the RAIDD interaction with
      endogenous caspase 2, attenuated trophic deprivation-induced apoptosis.
      Furthermore, downregulation of RAIDD by small interfering RNA led to inhibition
      of trophic deprivation-induced death, whereas death induced by DNA damage, which
      is not caspase 2-mediated, was not inhibited. Therefore, RAIDD, likely through
      interaction with caspase 2, is involved in trophic deprivation-induced neuronal
      apoptosis. This is the first demonstration of the involvement of RAIDD in
      apoptosis, and provides further support for the idea that apoptotic pathways in
      the same system may differ depending on the initiating stimulus.

PMID- 15947788
TI  - Regulatory phosphorylation of Bim: sorting out the ERK from the JNK.

PMID- 15947789
TI  - Bmf is a possible mediator in histone deacetylase inhibitors FK228 and CBHA
      induced apoptosis.
AB  - Histone deacetylase (HDAC) inhibitors modify transcription of selected genes and
      eventually induce apoptosis. However, molecular mechanisms for their proapoptotic
      activity remain unclear. We here demonstrate that HDAC inhibitors FK228 and CBHA
      preferentially upregulated the BH3-only protein Bmf in a broad range of cancer
      cells. In contrast, HDAC1 overexpression distinctly reduced Bmf expression. FK228
      induced histones H3 and H4 acetylation at Bmf promoter region, but not at its 3'
      region, suggesting that histone hyperacetylation causes Bmf transcriptional
      activation. Knockdown of Bmf transcripts rescued cells from FK228 or CBHA-induced
      cell death, disruption of mitochondrial membrane potential (DeltaPsim) and DNA
      fragmentation. Taken together, FK228 and CBHA activate Bmf transcription by
      histone hyperacetylation at its promoter region, and inhibition of this action
      decreased their proapoptotic activity, thereby highlighting a central role of Bmf
      in HDAC inhibitor-mediated apoptosis.

PMID- 15947790
TI  - Correlation between differentiation plasticity and mRNA expression profiling of
      CD34+-derived CD14- and CD14+ human normal myeloid precursors.
AB  - In spite of their apparently restricted differentiation potentiality,
      hematopoietic precursors are plastic cells able to trans-differentiate from a
      maturation lineage to another. To better characterize this differentiation
      plasticity, we purified CD14- and CD14+ myeloid precursors generated by 'in
      vitro' culture of human CD34+ hematopoietic progenitors. Morphological analysis
      of the investigated cell populations indicated that, as expected, they consisted
      of granulocyte and monocyte precursors, respectively. Treatment with
      differentiation inducers revealed that CD14- cells were bipotent granulo-monocyte
      precursors, while CD14+ cells appeared univocally committed to a terminal
      macrophage maturation. Flow cytometry analysis demonstrated that the conversion
      of granulocyte precursors to the mono-macrophage maturation lineage occurs
      through a differentiation transition in which the granulocyte-related
      myeloperoxidase enzyme and the monocyte-specific CD14 antigen are co-expressed.
      Expression profiling evidenced that the observed trans-differentiation process
      was accompanied by a remarkable upregulation of the monocyte-related MafB
      transcription factor.

PMID- 15947791
TI  - Bax limits adult neural stem cell persistence through caspase and IP3 receptor
      activation.
AB  - Neural stem cells in the mammalian brain persist and are functional well into
      adulthood. There is, however, little insight into mechanisms that control adult
      neural stem cell survival. Mice deficient in the proapoptotic molecule Bax
      exhibit increased numbers of multipotent progenitor cells in the adult
      subventricular zone. In vitro, these progenitors behave as neural stem cells and
      utilize Bax and caspase activation to direct cell death. We demonstrate that the
      predominate mechanism underlying caspase and Bax-mediated adult neural stem cell
      death lies in the modulation of calcium flux through interaction with the IP3
      receptor.

PMID- 15947792
TI  - Lipid microdomains contribute to apoptosis-associated modifications of
      mitochondria in T cells.
AB  - Plasma membrane lipid microdomains have been considered as a sort of 'closed
      chamber', where several subcellular activities, including CD95/Fas-mediated
      proapoptotic signaling, take place. In this work we detected GD3 and GM3
      gangliosides in isolated mitochondria from lymphoblastoid CEM cells. Moreover, we
      demonstrated the presence of microdomains in mitochondria by immunogold
      transmission electron microscopy. We also showed that GD3, the voltage-dependent
      anion channel-1 (VDAC-1) and the fission protein hFis1 are structural components
      of a multimolecular signaling complex, in which Bcl-2 family proteins (t-Bid and
      Bax) are recruited. The disruption of lipid microdomains in isolated mitochondria
      by methyl-beta-cyclodextrin prevented mitochondria depolarization induced by GD3
      or t-Bid. Thus, mitochondrion appears as a subcompartmentalized organelle, in
      which microdomains may act as controllers of their apoptogenic programs,
      including fission-associated morphogenetic changes, megapore formation and
      function. These results disclose a new scenario in which mitochondria-associated
      lipid microdomains can act as regulators and catalysts of cell fate.

PMID- 15947793
TI  - MIF loss impairs Myc-induced lymphomagenesis.
AB  - Macrophage migration inhibitory factor (MIF) is a potent regulator of
      inflammation and cell growth. Using the Emu-Myc lymphoma mouse model, we
      demonstrate that loss of MIF markedly delays the onset of B-cell lymphoma
      development in vivo. The molecular basis for this MIF-loss-induced phenotype is
      the perturbed DNA-binding activity of E2F factors and the concomitantly enhanced
      tumor suppressor activity of the p53 pathway. Accordingly, premalignant MIF-null
      Emu-Myc B-cells are predisposed to delayed S-phase progression and increased
      apoptosis. MIF-deficient lymphomas that do arise under these conditions contain
      frequent ARF deletions and p53 inactivating mutations. Conversely, MIF expression
      is retained in tumors developed by wild-type Emu-Myc animals, and the presence of
      one or both MIF alleles is sufficient to accelerate the development of Myc
      induced lymphomas. Collectively, these results indicate that MIF promotes Myc
      mediated tumorigenesis, at least in the B-lymphoid compartment, and implicate MIF
      as a mediator of malignant cell growth in vivo.

PMID- 15947796
TI  - Current concepts in macular degeneration: introduction.

PMID- 15947794
TI  - Endogenous activation of metabotropic glutamate receptors supports the
      proliferation and survival of neural progenitor cells.
AB  - The use of neural progenitor cells (NPCs) is limited by the incomplete knowledge
      of the extracellular signals regulating their proliferation and survival. We
      report that cultured mouse NPCs express functional mGlu3 and mGlu5 metabotropic
      glutamate receptors. Pharmacological blockade of both receptors reduced NPC
      proliferation and survival, whereas activation of mGlu5 receptors substantially
      enhanced cell proliferation. Adult mice lacking mGlu5 receptors or treated with
      mGlu5 or mGlu3 receptor antagonists showed a dramatic reduction in the number of
      dividing neuroprogenitors present in the subventricular zone and in the dentate
      gyrus of the hippocampus. These data disclose a novel function of mGlu receptors
      and offer new potential strategies for the optimization of cell replacement
      therapy in neurodegenerative disorders.

PMID- 15947797
TI  - Age-related macular degeneration: economic burden and value-based medicine
      analysis.
AB  - It can be estimated that 17,100 new cases of neovascular (wet) AMD and 180,000
      new cases of geographic-atrophy (dry) AMD occur in Canada annually. In addition
      to having a devastating effect on patients' lives, the condition causes
      significant adverse consequences for the economy. The deleterious effect of AMD
      on quality of life is markedly underestimated by ophthalmologists who treat
      patients with AMD, by non-ophthalmic physicians and by the public. In fact,
      patients with different degrees of severity of AMD have a perceived impairment of
      their quality of life that is 96% to 750% greater than the impairment estimated
      by treating ophthalmologists. Mild AMD causes a 17% decrease in the quality of
      life of the average patient, a decrease similar to that encountered with
      symptomatic human immunodeficiency virus infection or moderate cardiac angina.
      Moderate AMD produces a 40% decrease in quality of life, a decrease similar to
      that associated with permanent renal dialysis or severe cardiac angina. Very
      severe AMD causes a 63% decrement in quality of life, a decrease similar to that
      encountered with advanced prostatic cancer with uncontrollable pain or a severe
      stroke that leaves a person bedridden, incontinent and requiring constant nursing
      care. The adverse economic consequences of AMD include an annual $2.6 billion
      negative impact on Canada's gross domestic product. The return on investment is
      high for both current AMD therapies and research into new treatment modalities.

PMID- 15947798
TI  - Genetic aspects of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is a complex phenotype that has multiple
      causes, including genetic. This paper reviews pertinent single-gene disorders,
      polymorphisms in the human genome that modify disease severity, and maculopathies
      that provide insight into the pathogenesis of AMD and the function of the normal
      macula. The availability of DNA-based analysis for certain genes will likely
      increase the demand for genetic counselling of patients and families with AMD.
      Better knowledge of risks should help prevent blindness in these families.

PMID- 15947799
TI  - Comparison of stereoscopic digital imaging and slide film photography in the
      identification of macular degeneration.
AB  - BACKGROUND: This study compared the sensitivity and specificity of stereoscopic
      digital photography of the retina through a dilated pupil with a 45 degrees
      nonmydriatic camera and Joint Photographic Experts Group (JPEG) compression of
      the images with the sensitivity and specificity of 35-mm slide film photography
      in the identification of age-related macular degeneration (AMD). METHODS:
      Consecutive patients with a diagnosis of AMD were enrolled. Stereoscopic retinal
      images of the disc, macula and temporal macula were captured with a digital 45
      degrees nonmydriatic camera (then compressed into JPEG format) and with a
      standard fundus camera and slide film. A single retinal specialist graded both
      image formats in masked fashion, at least 1 month apart, using a modified Age
      Related Eye Disease Study (AREDS) severity scale. The digital images were
      displayed on a monitor and viewed with the use of liquid crystal display shutter
      glasses and stereo imaging software. The film images were mounted on a light box
      and graded with the use of a stereoviewer. Primary outcome measures included the
      presence or absence of AMD pathological features. Positive and negative
      predictive values (PPVs and NPVs), sensitivity, specificity and weighted kappaw
      statistics were calculated. RESULTS: We photographed 203 eyes (of 103 patients)
      with both digital and slide film cameras. Correlation of the 2 image formats was
      substantial in identifying AREDS level 3a or greater (kappaw=0.64, standard
      error=0.08, PPV=0.95, NPV=0.66, sensitivity=0.93, specificity=0.74) and excellent
      in identifying level 4b or greater (kappaw=0.83, standard error=0.05, PPV=0.81,
      NPV=0.98, sensitivity=0.94, specificity=0.94). INTERPRETATION: High-resolution
      stereoscopic, mydriatic, 45 degrees digital images captured with a nonmydriatic
      camera and JPEG compressed correlate well with stereoscopic slide film
      photographs in the identification of moderate to advanced AMD (AREDS level 3a or
      greater).

PMID- 15947800
TI  - Preferred retinal loci and macular scotoma characteristics in patients with age
      related macular degeneration.
AB  - Many patients with macular scotomas due to age-related macular degeneration do
      not perceive black spots in the visual field where the scotomas are located.
      Rather, they describe objects as "vanishing," "jumping out of nowhere" or "having
      blurry parts," or a combination of features. In addition, when the macular
      scotoma affects the fovea, the visual system uses 1 or more preferred retinal
      loci (PRLs) as a "pseudofovea" to perform visual tasks. Visual function testing
      with the scanning laser ophthalmoscope has provided a wealth of information
      regarding how patients perceive the visual world and how the oculomotor system
      directs eye movements. This article describes 2 specific functions of the
      oculomotor system, fixation stability and refixation precision, with data
      collected from normally sighted people and patients with visual field loss. The
      implications of the characteristics of PRLs and macular scotomas for clinical
      testing are discussed.

PMID- 15947801
TI  - Progression of visual loss and time between initial assessment and treatment of
      wet age-related macular degeneration.
AB  - PURPOSE: To determine whether the time elapsed from initial (referral) diagnosis
      of neovascular (wet) age-related macular degeneration (AMD) to assessment and
      treatment by a retinal specialist is associated with visual deterioration in the
      intervening period. METHODS: A prospective pilot study of 38 consecutive AMD
      patients who presented with newly diagnosed subfoveal choroidal
      neovascularization was conducted in a tertiary care retinal practice. All
      eligible subjects underwent clinical examination and digital fluorescein
      angiography at the time of assessment by a retinal specialist. Correlations were
      performed to assess the association between continuous independent variables and
      any visual deterioration since initial diagnosis. Multivariate linear regression
      models with stepwise techniques were used to evaluate any association between
      visual progression and time elapsed, while controlling for potential clinical
      covariates. RESULTS: Of the 38 patients, 32 (84%) met the inclusion and exclusion
      criteria; no differences in important variables were noted between those included
      and those excluded. The median time between initial diagnosis and referral
      assessment and treatment was 28 days (interquartile range=36.5 days); some degree
      of visual loss developed in 14 (44%) of the subjects. The elapsed time was
      correlated with progression of visual loss (r=0.50, p=0.003). Multivariate linear
      regression demonstrated that only time elapsed and lesion type based on
      fluorescein angiography were associated with progression of visual loss
      (R2=0.491, F(4,28)=6.744, p=0.001); lesion size, age and sex were not
      significantly associated with progression of visual loss. INTERPRETATION: Delay
      in assessment and treatment of new-onset wet AMD by a retinal specialist is
      associated with a higher risk of visual loss.

PMID- 15947802
TI  - Laser prophylaxis for age-related macular degeneration.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of
      severe and irreversible vision loss among people 50 years of age or older in many
      Western countries. Most of the available treatments for AMD are intended for the
      late stage, specifically for choroidal neovascularization (CNV). Effective
      preventive treatments could have an even greater impact on the vision of the
      millions of people at risk for vision loss from AMD. Drusen are typically the
      earliest lesions seen in patients with AMD and precede the development of CNV. In
      1973, Gass noted the disappearance of drusen in eyes that received laser
      photocoagulation, which led to the hypothesis that laser-induced drusen reduction
      could alter the natural course of AMD. METHODS: We reviewed relevant articles
      found through a search of MEDLINE through February 2005 by means of the following
      key words, alone or in combination: drusen, laser, photocoagulation, age-related
      macular degeneration, macula and choroidal neovascularization. RESULTS: Reports
      ranging from individual cases and case series to randomized controlled pilot
      studies have described various laser treatment protocols and their effects on
      eyes with high-risk drusen but no neovascular changes. These reports provide
      evidence that laser photocoagulation can induce drusen reduction. Although some
      investigators have reported a corresponding improvement in visual function,
      others have found no change or even worsening. The results in several of the
      larger randomized controlled studies suggest that CNV may occur at an increased
      rate in laser-treated eyes with high-risk drusen in patients who have neovascular
      AMD in the other eye. The long-term effects of laser treatment in patients with
      high-risk drusen in both eyes and no neovascular changes have yet to be
      determined. INTERPRETATION: The outcome of clinical trials such as the
      Prophylactic Treatment of Age-Related Macular Degeneration and the Complications
      of Age-Related Macular Degeneration Prevention Trial will help to determine the
      role of laser prophylaxis in patients with AMD.

PMID- 15947803
TI  - Rheopheresis for age-related macular degeneration: clinical results and putative
      mechanism of action.
AB  - BACKGROUND: Rheopheresis is being evaluated in a clinical trial. The rationale
      and available results are presented. METHODS: We reviewed the literature about
      the pathophysiology of age-related macular degeneration (AMD) that might support
      the use of rheopheresis. In addition, we reviewed the previously published
      results of the use of rheopheresis for AMD. RESULTS: There appears to be a
      diffusion barrier caused by accumulation of cross-linked proteins known as
      advanced macular oxidation products (AMOPS) in AMD. Rheopheresis allows removal
      of uncross-linked proteins and facilitates antioxidant entry into Bruch's
      membrane, preventing further accumulation of AMOPS. The Multicenter Investigation
      of Rheopheresis for AMD (MIRA-1), an ongoing double-masked randomized trial,
      should determine the efficacy of rheopheresis in preventing the progression of
      AMD. The interim results, from an analysis of visual acuity data for 43 patients,
      are encouraging, confirming the potential of rheopheresis as a therapeutic option
      for dry AMD. The benefit was evident immediately after treatment and remained
      essentially stable throughout the 12-month period of evaluation. Eyes with late
      stage, high-risk, dry AMD appeared to be at significant risk for substantial
      vision loss over the 12 months if not treated. Subgroup analysis demonstrated
      that the timing of rheopheresis in the course of a patient's disease may have a
      pronounced effect on outcome. INTERPRETATION: There appears to be a rationale for
      the use of rheopheresis in AMD. Further results of the clinical trial are
      awaited.

PMID- 15947804
TI  - Surgical management of age-related macular degeneration.
AB  - The development of increasingly refined vitreoretinal surgical techniques has
      resulted in a variety of surgical procedures for age-related macular degeneration
      (AMD). These have included submacular surgery with removal of choroidal
      neovascular membranes and subretinal blood, intraoperative lysis of feeder
      vessels, pneumatic displacement of subretinal blood and macular translocation
      surgery. The goals of these procedures have been to improve upon the poor natural
      history of exudative AMD and restore useful central vision. This article reviews
      the varied approaches, results and complications of the surgical management of
      AMD.

PMID- 15947805
TI  - Targeting angiogenesis, the underlying disorder in neovascular age-related
      macular degeneration.
AB  - Angiogenesis has a causal role in many diseases, including neovascular age
      related macular degeneration (AMD). Identification of key regulators of
      angiogenesis, including vascular endothelial growth factor (VEGF), fibroblast
      growth factor 2, pigment epithelium-derived growth factor, angiopoietins and
      extracellular matrix molecules, has facilitated the development of novel
      therapeutic agents that target the underlying pathological angiogenic process.
      Among these, VEGF serves as a "master switch" for many ocular neovascular
      conditions through its promotion of endothelial cell proliferation and survival,
      vascular permeability and ocular inflammation. Two anti-VEGF agents are now
      clinically available: bevacizumab, an antibody for metastatic colorectal cancer,
      and pegaptanib sodium, an aptamer for neovascular AMD. Unlike bevacizumab, which
      binds all VEGF isoforms, pegaptanib targets only VEGF165, the isoform responsible
      for pathological ocular neovascularization and thus an ideal target for treatment
      of AMD. Although other therapies targeting angiogenesis in AMD are in clinical
      development, to date, pegaptanib is the only therapy approved by the Food and
      Drug Administration of the United States for the treatment of all neovascular AMD
      and represents a valuable addition to the hitherto limited options available for
      patients.

PMID- 15947806
TI  - Drug pricing for a novel treatment for wet macular degeneration: using
      incremental cost-effectiveness ratios to ensure societal value.
AB  - OBJECTIVE: Health economic models can assist policy-makers in determining the
      value of novel treatments from the viewpoint of society. In this context, value
      is defined as the benefit of treatment, given its cost. A new treatment for wet
      age-related macular degeneration (AMD), juxtascleral administration of anecortave
      acetate, 15 mg for depot suspension (Retaane), is now in a late-phase clinical
      trial. In a theoretical analysis, we sought to determine the cost at which this
      treatment might offer economic value to society, using incremental cost
      effectiveness ratios (ICERs). METHODS: A series of 1-year cost-utility models was
      created for the investigational treatment and standard treatment (photodynamic
      therapy [PDT] with verteporfin [Visudyne]). Value to society was defined in terms
      of theoretical associated ICERs (in US dollars): $100,000 per quality-adjusted
      life-year (QALY), $50,000/QALY, $20,000/QALY and $0/QALY, the point of economic
      indifference. Models were created from the societal perspective and included a
      patient-derived utility assessment involving regression equations to estimate
      time trade-off preferences, event probabilities derived from a randomized
      clinical trial comparing the safety and efficacy of anecortave administration and
      PDT with verteporfin, decision analysis and relevant costing information.
      RESULTS: An ICER of $100,000/QALY would be associated with an anecortave cost of
      $3022/vial, an ICER of $50,000/QALY with an anecortave cost of $2986/vial and an
      ICER of $20,000/QALY with an anecortave cost of $2964/vial. The point of economic
      indifference between anecortave administration and standard therapy would occur
      with an anecortave cost of $2950/vial. INTERPRETATION: In theory, an anecortave
      cost of $2986/vial is associated with an ICER of $50,000/QALY, the threshold used
      by many health technology assessment and reimbursement agencies.

PMID- 15947807
TI  - Comparison of photodynamic therapy and transpupillary thermotherapy for subfoveal
      choroidal neovascularization due to age-related macular degeneration.
AB  - BACKGROUND: The purpose of this study was to compare photodynamic therapy (PDT)
      against subthreshold transpupillary thermotherapy (TTT) with a diode laser for
      subfoveal choroidal neovascularization secondary to age-related macular
      degeneration (AMD). METHODS: Patients with subfoveal choroidal neovascularization
      secondary to AMD were offered PDT as an initial intervention. If they declined
      PDT, then TTT was offered. RESULTS: We evaluated and followed 115 consecutive
      patients for an average of 1 year. The primary outcome measure was visual acuity,
      but the interventions were also compared on the basis of lesion size and
      angiographically determined lesion activity. Baseline comparisons between the 2
      treatment groups showed significant differences in pretreatment visual acuity,
      lesion size, and lesion composition. Univariate analysis of outcomes demonstrated
      equivalence between the treatment groups in final lesion size, angiographic
      activity, and visual acuity. Multivariate analysis also demonstrated equivalence
      between the treatment groups in final visual acuity while controlling for age,
      pretreatment visual acuity, and lesion category. Predominantly classic lesions
      were associated with poorer visual outcomes. INTERPRETATION: The PDT and TTT
      groups were equivalent in terms of all outcome parameters evaluated.

PMID- 15947808
TI  - Socioeconomic status and clinical features of patients undergoing photodynamic
      therapy or transpupillary thermotherapy for subfoveal choroidal
      neovascularization due to age-related macular degeneration.
AB  - BACKGROUND: The purpose of this study was to compare baseline clinical and
      socioeconomic features of patients undergoing self-funded photodynamic therapy
      (PDT) or government-funded subthreshold transpupillary thermotherapy (TTT) with a
      diode laser for subfoveal choroidal neovascularization secondary to age-related
      macular degeneration (AMD). METHODS: Between July 2000 and August 2001, 115
      patients with subfoveal choroidal neovascularization secondary to AMD were
      offered PDT as an initial intervention. If individuals believed that they could
      not afford or did not want PDT, then TTT was offered. In masked fashion, leakage
      pattern and lesion size were determined retrospectively from pretreatment
      angiograms. Baseline visual acuity was determined with autorefraction and
      subsequent Snellen testing. The mean income of each treatment group was estimated
      from the average sex-specific income for each subject's postal code, based on the
      1996 Canadian census data. The average education level for each subject's postal
      code was also determined. RESULTS: The patients who were not willing to pay for
      PDT had significantly worse macular disease before treatment (larger lesions and
      poorer visual acuity) and a significantly lower mean income than the patients who
      were willing to pay for PDT. INTERPRETATION: The severity of exudative choroidal
      neovascularization appears to be associated with lower socioeconomic status.

PMID- 15947809
TI  - Age-related macular degeneration: treating the whole patient.
AB  - Ophthalmologists can help to improve the quality of life for patients with age
      related macular degeneration (AMD) by treating the whole patient. Patients should
      be encouraged to seek psychiatric care for depression, especially if symptoms are
      persistent. They may also cope better with their vision loss by participating in
      AMD support groups. For earlier diagnosis of AMD, patients at high risk should be
      screened; if large drusen are present, nutritional suggestions can be made. Until
      treatments to prevent vision loss or to restore vision are available, these
      approaches provide optimal care.

PMID- 15947810
TI  - [The physician and the media].

PMID- 15947812
TI  - [What is the importance of plastic surgery in the planning of surgical incisions
      in gynecology?].

PMID- 15947814
TI  - [How the "CONSORT" recommendations can ensure the quality of clinical trial
      reports].

PMID- 15947815
TI  - [Benefits and risks of the andropause treatment].

PMID- 15947816
TI  - [Clinical and laboratory evolution of newborns of HIV-seropositive mothers].

PMID- 15947817
TI  - [Use of pneumococcal vaccines in children with type 1 diabetes mellitus].

PMID- 15947818
TI  - [Metastatic melanoma of the gallbladder mimicking Bladder Calculi].

PMID- 15947819
TI  - [Evaluation of school-books content on the subject of vaccines].
AB  - OBJECTIVES: Both school-books as well as teachers in elementary education play an
      important role in the dissemination of concepts on health education. To evaluate
      the content of the books used for elementary education with regard to their
      concepts and information on vaccination. METHODS: A total of 50 schoolbooks in
      the domains of Sciences and Biology was analyzed to verify their content on
      vaccination. The work was carried out by two fifth year students of medicine and
      also by a professor in the area of Pediatrics. RESULTS: Of the 50 books analyzed,
      17 (34%) had no information whatsoever on vaccination. Regarding content, of the
      33 books that did have information on vaccines, 19 (57.5%) had incorrect
      information: errors on the definition of vaccines, errors on the vaccination
      calendar, absence of content updating, omission of the content and inadequate
      illustration. Among the errors are: mention of inexistent vaccines (dengue) or in
      disuse (smallpox), the fallacy that vaccine is a remedy, vaccine indication only
      for children and association of vaccines with pain and discomfort. Moreover,
      regarding content, 26 books (78.7%) cited concept/definition of vaccines, 29/33
      (87.8%) associated vaccine with prevention of disease, 10/33 (30.3%) cited a
      basic calendar of vaccination and only 7/33 (21.2%) informed on vaccination in
      other age brackets other than the pediatric one. CONCLUSION: In spite of the
      importance of vaccination and notwithstanding the guidelines of MEC (Brazilian
      Education Ministry), more than half of the books analyzed had some misconception
      or wrong information on the subject.

PMID- 15947820
TI  - [Pediatricians and sleep-disordered breathing in the child].
AB  - OBJECTIVES: Assessment of opinions and practices of pediatricians concerning
      sleep-disordered breathing (SDB) in children. METHODS: Randomly 516 pediatricians
      were selected in the state of Sao Paulo, Brazil. A survey mailed to them included
      questions regarding: their professional profile, knowledge about SDB in
      childhood, opinions and practices for diagnosis and treatment of these diseases.
      RESULTS: 112 anonymous completed surveys were returned (21.7%). The teaching of
      SDB during medical school and pediatric residency raining was considered
      unsatisfactory respectively by 65.2% and 34.8% of the pediatricians. Forty-nine
      respondents (43.8%) rated their knowledge about SDB in children as regular, 39
      (34.8%) as good and 17 (15.2%) as unsatisfactory. The most important sleep
      related questions were: mouth breathing, breathing pauses, sleep amount,
      excessive daytime sleepiness and nocturnal wheezing. Clinical aspects regarded as
      the most significant for suspecting obstructive sleep apnea syndrome (OSAS) were:
      breathing pauses, adenoid hypertrophy, mouth breathing, craniofacial anomaly and
      snoring. The most frequent practices for evaluation of OSAS in children were:
      cavum radiography with referral to an otorhinolaryngologist (25%) and nocturnal
      pulse oximetry (14.2%). Only 11.6% of pediatricians recommended overnight
      polysomnography and 4.5%, nap polysomnography. The most effective practices for
      SDB were considered to be: adenoidectomy and adenotonsillectomy, parents
      counseling, weight loss and sleep hygiene. CONCLUSIONS: There is a gap between
      research on SDB in childhood and pediatric practice.

PMID- 15947821
TI  - [Profile of a medical auditing group in the state of Rio Grande do Sul].
AB  - BACKGROUND: This paper aims to determine the profile of the medical auditor in
      the State of Rio Grande do Sul, Brazil, based upon a group of physicians who
      participated in the post-graduation courses of Unimed Foundation Health Auditing,
      in the cities of Porto Alegre and Caxias do Sul, together with other
      professionals performing the same activity in the State of Rio Grande do Sul.
      METHODS: A historical review, a study of the laws and norms that guide the role
      of the Medical Auditor is presented as well as a review of the literature on
      medical auditing in Brazil. A non identifiable questionnaire was administered,
      where questions on personal data and professional training were made, as well as
      others related to personal satisfaction, health and well-being. RESULTS: The
      questionnaire was answered by 71 Medical Auditors, with a total of 85 positions
      in medical auditing at several workplaces. 83.8% are male, ages ranging from 41
      to 50 years (38%), on the average they had been graduated for 21.96 +/- 7.68
      years, performing medical auditing activities for 7.24 +/- 6.62 years and 88.7%
      hold a medical academic title and/or medical specialization courses in several
      areas. In the group researched, 25.37% are formally employed 60% are personally
      and professionally satisfied and are physically well. In the interviewed group,
      there are no physicians under 33 years of age nor any graduated for less than 7
      years. CONCLUSIONS: A high level of medical education, specialization and
      updating is evident among the Medical Auditors that were interviewed. Data from
      the present study will contribute for the definition of the Brazilian Medical
      Auditor's Profile.

PMID- 15947822
TI  - [Swallowing after chemotherapy and radiotherapy for laryngeal and hypopharyngeal
      carcinomas].
AB  - The main goals of the larynx preservation protocol are eradication of cancer and
      preservation of a functional larynx with maintenance of respiration, phonation
      and swallowing. Few studies, however have addressed functional outcomes.
      OBJECTIVE: Functional evaluation of oropharyngeal swallowing in patients enrolled
      in a larynx preservation protocol at the Hospital do Cancer AC Camargo. METHODS:
      Evaluation of swallowing was performed by videofluoroscopy in 31 patients,
      focusing on: oropharyngeal motility disorders, stasis, laryngeal penetration,
      aspiration and severity of dysphagia. RESULTS: Swallowing analysis: 5 patients
      showed inefficient bolus preparation, 14 had changes in the bolus propulsion; 23
      patients had a reduced laryngeal elevation, 26 presented with stasis in the
      vallecula and 14 with stasis in hypopharynx. Nine patients presented silent
      aspiration. We detected functional swallowing in 11 patients; mild dysphagia in
      7; mild/moderate in 7; moderate in 3 and severe dysphagia in 3. CONCLUSION:
      Larynx preservation results in changes of swallowing, ranging in their majority
      from discrete to moderate. Some patients, however, developed severe dysphagia,
      and oral feeding was not possible.

PMID- 15947823
TI  - [Clinical and laboratory evolution of children born to HIV positive mothers].
AB  - The vertical transmission of HIV (Human Immunodeficiency Virus) has become the
      main target of prophylactic Zidovudina (AZT) therapy during gestation,
      parturition as well as for the newborn. BACKGROUND: To characterize the clinical
      and laboratory evolution of HIV exposed children. METHODS: Prospective study of
      64 HIV exposed children, classified into two groups. Group A, made up of 23 pairs
      of mothers and newborns, who did not receive AZT; Group B, made up of 41 pairs,
      who received AZT at some stage of prophylaxis. RESULTS: The average maternal age
      was 26.8 years, the use of illicit drugs occurred in 17.2% of the pregnant women,
      twenty (31.3%) of the women had diseases. Between the groups there were no
      significant differences related to prenatal frequency of maternal illnesses,
      birth body dimensions and growth sequence. Both study groups presented with
      similar lymphocyte and blood counts. On the average, seroreversion took place at
      16 months. Vertical transmission occurred in 6 children (9.3%), none of the
      children in the subgroup who received prophylaxis during all phases were
      infected. CONCLUSIONS: The prophylactic therapy with AZT during all the periods
      recommended and the long term follow-up of the HIV exposed children constitute
      one of the best strategies for prevention of the acquired immunodeficiency
      syndrome (AIDS) in infants.

PMID- 15947824
TI  - [Nutritional support for malnourished hospitalized children: experience of a
      referral center, Sao Paulo, Brazil].
AB  - AIM: To study anthropometric development, nutritional support and mortality rate
      of malnourished children hospitalized in a referral center. METHODS: In a
      retrospective study we surveyed 98 hospitalized malnourished children (ZW<--2)
      with no chronic disease. Data collected was: birth weight, gestational age,
      length of exclusive breast feeding, diagnosis at admission, formula used (type,
      delivery route and feeding tolerance) and length of stay. Weight and height were
      controlled at admission and discharge. To classify and evaluate nutritional
      rehabilitation we used the Z-score: weight-for-age (ZW), height-for-age (ZH),
      weight-for-height (ZW/H). The nutritional therapy used was based on the World
      Health Organization (WHO) guidelines, with minor modifications. All chosen
      formulas were industrialized: lactose-free polymeric formula (PLF) for children
      with diarrhea, low lactose polymeric formula (PLL) for children without diarrhea
      and cow's milk hydrolysate (CMH) for sepsis or chronic diarrhea. At the
      rehabilitation phase, all children were given the PLL formula. STATISTICAL
      ANALYSIS: Student's t and chi-square tests. RESULTS: The median of age and length
      of stay were 9.8 months and 17 days, respectively and the mortality rate was of
      2%. Diarrhea and/or pneumonia were diagnosed at admission in 81.6% of the
      children. An improvement of 17.3 % ZW, 82.7 % ZH and 92.2 % ZW/H was observed.
      PLF was more frequently given at admission (47.4%) while CMH was given to only
      7.4% of the children. Twenty-four percent of the children were tube fed and 5.1 %
      received parenteral nutrition. Tolerance of the initial formula was considered
      good in 66.7% of cases. CONCLUSIONS: The WHO guidelines were effective in the
      nutritional therapy of severely malnourished hospitalized children, resulting in
      good nutritional rehabilitation with low mortality rates.

PMID- 15947825
TI  - [Treatment of discitis in the child].
AB  - BACKGROUND: The authors reviewed nine patients presenting with discitis during
      infancy, demonstrating that its diverse forms of presentation lead to a delayed
      and difficult diagnosis. METHODS: This study reports that initial radiographs may
      not show any alterations, enhancing the importance of scintillography or magnetic
      resonance for these cases. RESULTS AND CONCLUSIONS: One patient was submitted to
      surgical treatment for lumbar canal decompression due to the presence of a disk
      abscess. The remaining patients were treated conservatively only with an
      appropriate antibiotic therapy, immobilization and restriction of physical
      activity. All of the young patients had a satisfactory evolution and stated no
      complaints about sequels during their final evaluation.

PMID- 15947826
TI  - [Prostate cancer dedifferentiation following antiandrogen therapy: a
      morphological finding or an increased tumor aggressiveness?].
AB  - BACKGROUND: Neoadjuvant androgen deprivation in prostate cancer induces tumor
      volume regression but does not improve outcome of the patient. A possible
      explanation for this phenomenon could be an increase of the residual tumor
      aggressiveness brought about by antiandrogen therapy. The purpose of the present
      study was to evaluate the frequency of tumor dedifferentiation following androgen
      blockade in prostate cancer and to determine if the remaining tumor shows signs
      of increased aggressiveness. METHODS: Thirty patients bearing locally advanced
      prostate cancer (stages T2c - T3) were submitted to neoadjuvant anti-androgenic
      therapy during four months followed by radical prostatectomy. Gleason scores from
      biopsy and surgical specimens were compared. Furthermore, the cell proliferation
      index was evaluated by immunohistochemistry assay for PCNA, tests with strong
      nuclear staining were considered positive. The percentage of positive nuclei,
      counted in 500 cells, was determined in several categories of the Gleason score
      from surgical specimens. RESULTS: In 11(37%) surgical specimens the Gleason score
      was equal or lower than that found in the biopsy and in 19 (63%) the total score
      was higher in the surgical specimens (p<0.05). The median of PCNA expression was
      4.5%, 10%, 12% and 14% in Gleason scores 2-4, 5-6,7 and 8-10, respectively
      (p>0.05). The median of cell proliferation indexes was 9% for glandular or
      specimen confined tumors and was 17% for extraprostatic tumors (p<0.05).
      CONCLUSION: The lower Gleason score was found in almost 2/3 of patients submitted
      to antiandrogen therapy. However, the cell proliferation index measured by PCNA
      was the same for tumors with lower or higher Gleason scores. It seems that cell
      dedifferentiation seen after neoadjuvant androgen deprivation represents a mere
      morphologic phenomenon and not a real increase in tumor aggressiveness.

PMID- 15947827
TI  - Why Brazil does not have an epidemic of chronic diseases: some answers from
      cardiovascular diseases.

PMID- 15947829
TI  - Preoperative laboratory evaluation of patients aged over 40 years undergoing
      elective non-cardiac surgery.
AB  - CONTEXT AND OBJECTIVE: Although it is generally agreed that a medical history and
      physical examination should be obtained as part of preoperative evaluation, there
      is still substantial controversy about the additional benefits of preoperative
      screening tests. The objective of the present study was to determine the
      percentage of abnormalities on laboratory tests among a population that underwent
      non-cardiac surgery and to correlate these tests with changes in preoperative
      evaluation management. DESIGN AND SETTING: Cross-sectional study, carried out in
      a University Hospital. METHODS: 991 patients aged over 40 years undergoing
      elective non-cardiac surgery from July 1997 to January 2000 were studied. Blood
      cell count, serum sodium, potassium, urea and creatinine, prothrombin, thrombin
      and partial thromboplastin time, electrocardiogram and chest X-ray were
      evaluated. RESULTS: Out of the 957 electrocardiograms performed, some type of
      abnormality was found in 504 cases (50.9%) and, among the 646 chest X-rays
      requested, 271 (42.0%) displayed alterations. Laboratory tests showed abnormal
      values ranging from 5.1% (prothrombin time) to 41.0% (hematocrit). Increased
      percentages of abnormal tests with increasing patient age were also observed.
      CONCLUSIONS: Although there were substantial numbers of screening test
      abnormalities in preoperative evaluations, these results seldom interfered in
      patient management.

PMID- 15947830
TI  - Red cell aspartate aminotransferase saturation with oral pyridoxine intake.
AB  - CONTEXT AND OBJECTIVE: The coenzyme of aspartate aminotransferase is pyridoxal
      phosphate, generated from fresh vegetables containing pyridoxine. Vitamin B6
      responsive sideroblastic anemia, myelofibrosis and Peyronies syndrome respond to
      high pyridoxine doses. The objective was to investigate the oral pyridoxine oral
      dose that would lead to maximized pyridoxal phosphate saturation of red cell
      aspartate aminotransferase. DESIGN AND SETTING: Controlled trial, in Hematology
      Division of Instituto Adolfo Lutz. METHODS: Red cell aspartate aminotransferase
      activity was assayed (before and after) in normal volunteers who were given oral
      pyridoxine for 15-18 days (30 mg, 100 mg and 200 mg daily). In vitro study of
      blood from seven normal volunteers was also performed, with before and after
      assaying of aspartate aminotransferase activity. RESULTS: The in vivo study
      showed increasing aspartate aminotransferase saturation with increasing
      pyridoxine doses. 83% saturation was reached with 30 mg daily, 88% with 100 mg,
      and 93% with 200 mg after 20 days of oral supplementation. The in vitro study did
      not reach 100% saturation. CONCLUSIONS: Neither in vivo nor in vitro study
      demonstrated thorough aspartate aminotransferase saturation with its coenzyme
      pyridoxal phosphate in red cells, from increasing pyridoxine supplementation.
      However, the 200-mg dose could be employed safely in vitamin B6-responsive
      sideroblastic anemia, myelofibrosis and Peyronies syndrome treatment. Although
      maximum saturation in circulating red cells is not achieved, erythroblasts and
      other nucleated and cytoplasmic organelles containing cells certainly will reach
      thorough saturation, which possibly explains the results obtained in these
      diseases.

PMID- 15947831
TI  - Evaluation of effectiveness of 10% polyvinylpyrrolidone-iodine solution against
      infections in wire and pin holes for Ilizarov external fixators.
AB  - CONTEXT AND OBJECTIVE: Superficial infection at wire and pin insertions in the
      skin is a frequent disorder among patients utilizing the Ilizarov method. The
      objective of this study was to evaluate the effectiveness of daily topical
      application of 10% polyvinylpyrrolidone-iodine solution against infections of the
      holes for Kirschner wires and Schanz pins among patients using Ilizarov external
      fixators, in comparison with cleaning these holes only with 0.9% sterile
      physiological saline solution. DESIGN AND SETTING: Controlled randomized clinical
      trial, in the Orthopedics and Traumatology Outpatient Clinic, Hospital Sao Paulo,
      and Orthopedics and Traumatology Center of Jundiai. METHODS: 30 patients were
      treated using the Ilizarov technique: 15 were instructed to apply 0.9%
      physiological saline dressing on the wire and pin insertions and 15 to apply 0.9%
      physiological saline plus 10% polyvinylpyrrolidone-iodine. Patients were
      evaluated at outpatient return visits for identification of signs and symptoms of
      superficial infection at wire and pin insertion sites. Samples were collected
      from cases of purulent exudate secretion, for culturing and clinical tests.
      RESULTS: The chi-squared and Fischer exact tests were applied, but no
      statistically significant association between the intervention of topical
      polyvinylpyrrolidone-iodine solution and the prevention of infections at wire and
      pin insertions could be found. CONCLUSIONS: Topical 10% polyvinylpyrrolidone
      iodine solution applied daily to Kirschner wire and Schanz pin insertions did not
      reduce the incidence of superficial infection at these holes, in comparison with
      mechanical removal of dirt using 0.9% physiological saline solution.

PMID- 15947832
TI  - Lack of association between nutritional status and change in clinical category
      among HIV-infected children in Brazil.
AB  - CONTEXT AND OBJECTIVE: Malnutrition is common among HIV-infected children. Our
      objective was to study the occurrence of malnutrition and its relationship with
      changes in clinical category among HIV-infected children. DESIGN AND SETTING:
      Longitudinal study, at the Pediatrics Department and Pediatrics Investigation
      Center (CIPED), Faculdade de Ciencias Medicas da Universidade Estadual de
      Campinas (Unicamp). METHODS: We reviewed the hospital records of 127 vertically
      HIV-infected children. Anthropometric measurements were obtained at the beginning
      of follow-up, at clinical category change and five months later. These were
      converted to z-scores of weight/age, height/age and weight/height. Data were
      presented as means, standard deviations, frequency counts and percentages. The
      Wilcoxon and Kruskal-Wallis tests and odds ratios were used in the analysis.
      RESULTS: We found that 51 (40.2%) were undernourished and 40 (31.5%) were
      stunted, with higher risk of being included in clinical category C. There was an
      association between nutritional condition and the clinical categories of the
      Centers for Disease Control classification (1994), and with age at symptom onset
      (except for height z-score). During follow-up, 36 patients (28.4%) changed their
      clinical category, which occurred early among the undernourished patients. The
      group that changed its clinical category maintained the same z-score distribution
      for weight, height and weight/height throughout follow-up. CONCLUSION: Aids
      manifestation severity was associated with nutritional status and with age at
      symptom onset, but change in clinical category was not followed by worsening of
      nutritional status.

PMID- 15947833
TI  - Type 2 diabetes: prevalence and associated factors in a Brazilian community--the
      Bambui health and aging study.
AB  - CONTEXT AND OBJECTIVE: Diabetes is an increasing cause of death in developing
      countries. Our objective was to describe the prevalence and clinical factors
      associated with diabetes and impaired fasting glycemia among adults (18-59 years)
      and elderly adults (60+ years). DESIGN AND SETTING: Population based, cross
      sectional study in Bambui, Brazil. METHODS: 816 adult and 1,494 elderly
      participants were interviewed; weight, height and blood pressure measured; and
      blood samples collected. Diabetes was defined as plasma fasting glucose > 126
      mg/dl and/or use of hypoglycemic agents; impaired fasting glycemia as glycemia of
      110-125 mg/dl. Associations were investigated using multinomial logistical
      regression (reference: fasting glycemia < 109 mg/dl). RESULTS: Among the elderly,
      218 (14.59%) presented diabetes and 199 (13.32%) impaired fasting glycemia,
      whereas adult prevalences were 2.33% and 5.64%. After multinomial analysis,
      diabetes remained associated, for adults, with increased waist-to-hip ratio and
      total cholesterol > 240 mg/dl; for elderly adults, with family history of
      diabetes, body-mass index of 25-29 kg/m(2), body-mass index > 30 kg/m(2),
      increased waist-to-hip ratio, low HDL-cholesterol triglyceridemia of 200-499
      mg/dl and triglyceridemia > 500 mg/dl. Among adults, impaired fasting glycemia
      remained associated negatively with male sex and positively with ages of 40-59
      years, physical inactivity and increased waist-to-hip ratio; among the elderly,
      with alcohol consumption, overweight, obesity and triglycerides > 200 mg/dl.
      CONCLUSIONS: The results reinforce the importance of interventions to reduce
      physical inactivity, alcohol consumption, obesity and dyslipidemia, so as to
      prevent increasing incidence of diabetes.

PMID- 15947834
TI  - The general practitioner and mental health problems: challenges and strategies
      for medical education.
AB  - CONTEXT AND OBJECTIVE: Within the context of primary health care and mental
      disorders, our aim was to study the opinions of general practitioners regarding
      attendance of people with mental health problems. DESIGN AND SETTING: Qualitative
      focal group study among primary care services in the cities of Porto Alegre and
      Parobe, State of Rio Grande do Sul. METHODS: A deliberately selected sample of 41
      general practitioners who were working in basic health services met in focal
      groups. Two videos were presented, which simulated consultations for patients
      with depression and psychoses. The discussions about the identification and
      handling of mental health problems were recorded and assessed via content
      analysis. RESULTS: The opinions related to the difficulties of diagnosing and
      treating mental problems, the involvement of relatives in caring for patients,
      the difficulty of compliance with the treatment, the uncertainty experienced by
      physicians and the difficulty of referring patients to specialized services.
      CONCLUSIONS: The general practitioners indicated that they perceived the mental
      health problems among their clientele, but the diagnosis and treatment of these
      problems are still seen as a task for specialists. The challenge of continuing
      education on mental health requires methods of interactive and critical teaching,
      such as the problem-based approach.

PMID- 15947835
TI  - Homeopathy and acupuncture teaching at Faculdade de Medicina da Universidade de
      Sao Paulo: the undergraduates' attitudes.
AB  - CONTEXT AND OBJECTIVE: Homeopathy and acupuncture, although recognized as medical
      specializations in Brazil, are not taught in most medical schools. The objective
      was to evaluate undergraduate attitudes towards them following their inclusion as
      optional disciplines at Faculdade de Medicina da Universidade de Sao Paulo
      (FMUSP) in 2002. DESIGN AND SETTING: Questionnaire, at FMUSP. METHODS: 484
      students answered a self-administered questionnaire on these therapies, regarding
      their interest in learning, the teaching methods, their knowledge/experience (or
      that of someone close to them) and how it was acquired, the main indicators and
      general effectiveness of these therapies, and the possibilities for offering and
      integrating them within public healthcare units. RESULTS: Over 85% of the
      students considered that homeopathy and acupuncture should be included in
      curricula, as options (72%) or compulsorily (19%); 56% showed great interest in
      learning about them. Although 76% had little or no knowledge, 67% believed that
      these therapies had some effectiveness, and that chronic diseases (37%) or even
      chronic and acute diseases (29%) would be the main indicators for their use.
      Around 35% were receptive towards offering public primary care using both
      therapies, while 34% thought these treatments should also be available in
      hospitals and 60% believed they could be integrated with conventional medical
      practices. CONCLUSION: The medical students were interested in learning the
      principles of homeopathy and acupuncture, were able to observe and report on the
      effectiveness of these treatments and defended the use of these medical
      specializations within public healthcare.

PMID- 15947836
TI  - Bone disease in patients with chronic kidney disease under conservative
      management.
AB  - CONTEXT AND OBJECTIVE: Few studies have focused on bone disease in patients with
      chronic kidney disease under conservative treatment. The objective was to
      evaluate bone disease in patients with chronic kidney disease. DESIGN AND
      SETTING: Case series, at the Nephrology Division, Hospital Universitario Pedro
      Ernesto. METHODS: 131 patients with creatinine clearance from 10 to 60
      ml/min/1.73 m(2) were followed up for at least one year. Serum creatinine,
      albumin, calcium, phosphorus, alkaline phosphatase, total CO2 (tCO2), intact
      parathyroid hormone (iPTH), and alkaline phosphatase were measured. Creatinine
      clearance was calculated from 24-hour urine creatinine measurements and protein
      ingestion estimates from urea assays. RESULTS: Patients presenting creatinine
      clearance < 30 ml/min/1.73 m(2) had higher iPTH values, but normal serum levels
      for calcium, phosphorus, alkaline phosphatase and tCO2. Patients presenting iPTH
      values of twice the normal upper limit (144 pg/ml) showed lower tCO2 values. Bone
      alkaline phosphatase was evaluated in 37 patients with creatinine clearance < 30
      ml/min/1.73 m(2), showing correlation with alkaline phosphatase but not with
      parathyroid hormone. Bone biopsy on nine patients with creatinine clearance < 30
      ml/min/1.73 m(2) and iPTH > 144 pg/ml showed osteitis fibrosa (4), mild lesion
      (4) and high turnover (1). CONCLUSION: The present data suggest the importance of
      early control for iPTH and metabolic acidosis, among patients under conservative
      management for chronic kidney disease, in order to prevent complications related
      to bone disease.

PMID- 15947837
TI  - Iron deficiency anemia in children: a challenge for public health and for
      society.
AB  - Iron deficiency anemia is the principal nutritional dearth in the world, and it
      especially affects children and pregnant women in developing countries. This
      paper presents a survey of the literature in this area, with the aim of providing
      a brief overview regarding the occurrence of iron deficiency anemia in Brazil.
      The article describes the etiology of the disease, the risk groups, the high
      prevalence of anemia in several areas of Brazil, and also the consequences of
      iron deficiency in children. The paper also shows some ways to control iron
      deficiency anemia and some intervention programs applied in Brazilian cities for
      curing and/or preventing this disease. The article concludes by emphasizing the
      need to establish strategies and treatments in our country that are based on a
      policy that brings together not only governmental administration but also all the
      community.

PMID- 15947838
TI  - Diabetes mellitus in a young Amazon Indian child.
AB  - CONTEXT: Although type 2 diabetes has been described among American Indian
      children, no case of type 1 diabetes has been reported in the literature. CASE
      REPORT: We report the first case of diabetes in a South American Indian child
      from the tropical rainforest, who was positive for IA2 autoantibodies and genetic
      markers of susceptibility to type 1 diabetes, but also demonstrated residual beta
      cell function four years after diagnosis.

PMID- 15947839
TI  - Brazilian Society of Infectious Diseases: 25 years!

PMID- 15947840
TI  - Performance of an immunoenzymatic assay for Cryptosporidium diagnosis of fecal
      samples.
AB  - We evaluated the diagnostic performance of a Cryptosporidium immunoenzymatic
      assay (ELISA). Fecal samples were collected from 94 HIV-seropositive patients.
      All specimens were processed with a commercially-available ELISA to detect C.
      parvum specific coproantigen and with a modified Ziehl-Neelsen stain (ZNm)
      microscope exam. Overall, sensitivity of the immunoenzymatic test was 100%, with
      a specificity of 96%; positive and negative predictive values were 89% and 100%,
      respectively. The commercial ELISA and ZNm proved to be valuable diagnostic tools
      for Cryptosporidium infection.

PMID- 15947841
TI  - Spontaneous inflammatory pelvic disease in adult non-castrated female rats
      treated with estrogen.
AB  - The adaptive immune response of the genital tract is under the control of sexual
      steroids; however, the influence of sex hormones on innate immune mechanisms of
      the genital mucosa are only beginning to be understood. We found that long-term
      estrogen treatment increases the risk for inflammatory pelvic diseases in adult
      non-castrated female rats. Female rats (110 g to 130 g) received estrogen (10
      rats; 17-beta estradiol, 50 mg pellet; 10 rats: subcutaneous weekly injection of
      estradiol valerate 0.166 mg/kg). Ten rats received a pellet of 17-beta estradiol
      and were treated with amoxicillin, 50 mg/kg after the 90th day of exposure to
      estrogen. Three control groups of ten rats were also used. The estrogen-treated
      rats developed an inflammatory pelvic disease, with abscess formation after the
      third month of hormonal treatment. All the surviving animals were killed after
      six months of hormonal exposure. Among 15 survivors of the two groups that
      received estrogen 13 animals presented tuboovarian abscesses. Among eight
      survivors of the group treated with amoxicillin, six had tuboovarian abscesses.
      None of the 30 control rats presented macro or microscopic signs of inflammatory
      disease in the uterus, tubes or ovaries. We conclude that estrogen impairs the
      defense mechanisms of the genital tract of non-castrated female rats, enhancing
      bacterial growth in the vagina and ascending infection to the uterus, tubes and
      ovaries.

PMID- 15947842
TI  - Regional patterns of the temporal evolution of the AIDS epidemic in Brazil
      following the introduction of antiretroviral therapy.
AB  - We examined the characteristics of the AIDS epidemic in the northeastern region
      of Brazil, comparing it to the epidemic in Brazil as a whole, and to the state of
      Sao Paulo, with respect to the temporal evolution of morbidity and mortality
      during the period 1990 to 1999, using information from communicable disease
      reports and mortality records. Since 1996, the incidence rate of AIDS in adults
      in Brazil as a whole and in Sao Paulo has been showing a trend towards stability,
      whereas in the Brazilian northeast the incidence rates of the disease continue to
      grow. In the northeast, sexual transmission is responsible for more than 80% of
      cases, injectable drug users (IDU) comprising only a small percentage of cases.
      There is a greater incidence of AIDS among groups with lower educational levels
      throughout the country. The comparative analysis of cases of AIDS and of deaths
      from AIDS shows growth, both in the number of cases and in the number of deaths;
      however, from 1996 onwards there has been a progressive reduction in the number
      of deaths in all regions analyzed. With respect to the incidence of cases of the
      disease acquired by vertical transmission, a significant growth trend can be seen
      in all regions for cases born in the period 1990-6, but in 1997 temporal analysis
      showed evidence of a reduction in this growth. In conclusion, temporal changes
      have occurred in the AIDS epidemic in Brazil, which has been showing a trend
      towards stability since 1996, when potent ARV therapy was introduced. However,
      this deceleration is not homogenous throughout all the regions.

PMID- 15947843
TI  - Prospective study on the prevention of vertical transmission of HIV in Campo
      Grande, Mato Grosso do Sul, Brazil, from 1996 to 2001.
AB  - This prospective study, involving 76 pregnant women infected with HIV, paired
      with their 79 exposed infants, was carried out between May 1996 and October 2001,
      at the Reference Department for Pregnant Women Infected with HIV in Campo Grande,
      Mato Grosso do Sul. The mean age of the pregnant women was 24 years; 88% (67/76)
      apparently were infected due to sexual practices; 88% (67/76) were housewives;
      823% (63/76) graduated from junior high school; 14.5% (11/76) reported co
      infection with Hepatitis C, 9.2% with Syphilis; 51% (39/76) learned the diagnosis
      during prenatal care; 67% (51/76) reported HIV clinical symptomatology and 9.2%
      (7/76) reported opportunistic infections. Elective cesareans were performed in
      57% (43/76). The mean gestational age at delivery was 38 weeks and we found 12.5%
      (10/80) pronatis; 97% (74/76) had a ruptured membrane time after less than four
      hours and one child (1.3%) was nursed. ACTG 076 Protocol (AIDS Clinical Trial
      Group 076) was used in 80% (61/76) of the pregnant women, with 100% adherence;
      62% (38/61) used zidovudine plus another antiretroviral in the gestation; 92%
      (73/79) of the infants used zidovudine after the birth and 19% (14/73) used
      zidovudine and lamivudine. The transmission rate in this study was 2.5%.

PMID- 15947844
TI  - Detection of hepatitis C virus RNA in saliva samples from patients with seric
      anti-HCV antibodies.
AB  - We examined the frequency of HCV-RNA in saliva samples from anti-HCV positive
      patients. Both plasma and saliva samples from 39 HCV patients (13 with normal
      liver enzymes, 19 with abnormal liver enzymes and 13 with cirrhosis) were
      investigated. Stimulated saliva and fresh plasma were centrifuged (900 x g,10
      min) and stored at -70 degrees C, after the addition of guanidine isothiocyanate
      RNA extraction buffer. HCV-RNA was detected by RT-nested-PCR (amplification of
      HCV-cDNA for two rounds, using HCV primers 939/209 and 940/211). HCV genotyping
      was carried out by RFLP (using Mva I and Hinf 1 or Hae III and Rsa I restriction
      enzymes). Thirty-two out of 39 (82%; 95% CI=70-94%) anti-HCV-positive patients
      had HCV-RNA in plasma samples. Eight out of 39 (20.5%; 95% CI=6.6-34.4%) had HCV
      RNA in the saliva. The HCV genotype in saliva samples from these patients matched
      the genotype found for plasma HCV-RNA. No significant correlation between the
      presence of HCV and either age, gender, HCV genotype or any risk factor for HCV
      infection was found. The observed prevalence (20.5% of anti HCV positive patients
      or 25% of the patients with HCV-RNA in plasma) was lower than that previously
      reported from other countries. The low frequency of HCV-RNA in saliva samples
      observed in our study may be due to the use of cell-free saliva. Other authors
      reporting higher frequencies of HCV-RNA in saliva used whole saliva, without
      centrifugation.

PMID- 15947845
TI  - Combined use of Western blot/ELISA to improve the serological diagnosis of human
      tuberculosis.
AB  - Two recombinant antigens and a crude bacterial antigen of a wild M. tuberculosis
      strain were used to detect specific IgG antibodies in sera from 52 patients with
      pulmonary tuberculosis, confirmed by an acid-fast smear and serum culture of
      these patients and that of 25 contacts. The patients were not infected with HIV.
      We evaluated the sensitivity and specificity of ELISA, based on the recombinant
      TbF6 and TbF6/DPEP antigen and a search for reactivity patterns in the Western
      blot technique, using whole mycobacterium antigen. Serum samples from 22 healthy
      individuals and from 30 patients with lung diseases other than tuberculosis were
      used as controls. The best ELISA results were obtained with the TbF6/DPEP antigen
      combination, which gave 85% sensitivity and 91% specificity. ELISA sensitivity
      improved from 85% to 92% when the Western blot results were used. Western blot
      specificity was 100% when antibody reactivity with different antigenic bands was
      analyzed and associated. The association of TbF6/DPEP antigens used in ELISA with
      specific patterns of reactivity determined by Western blot can help make an
      identification when classic methods for the diagnosis of pulmonary tuberculosis
      are not sufficient.

PMID- 15947846
TI  - Antimicrobial susceptibility in intensive care units: MYSTIC Program Brazil 2002.
AB  - OBJECTIVE: Establish the susceptibility pattern of Gram-negative bacteria causing
      infections in ICU patients, MYSTIC Program Brazil 2002. MATERIAL AND METHODS:
      Gram-negative bacteria (n = 503) causing nosocomial infections were collected at
      seven Brazilian centers. The central laboratory confirmed the identification and
      performed the susceptibility tests by E-test methodology (AB Biodisk, Solna,
      Sweden) for meropenem, imipenem, ciprofloxacin, ceftazidime, cefepime,
      cefotaxime, piperacillin/tazobactam, gentamicin, and tobramycin. Interpretation
      criteria used were according to National Committee for Clinical Laboratory
      Standards (NCCLS). RESULTS: Pseudomonas aeruginosa (33%) was the most frequently
      isolated, followed by A. baumannii (17.1%), K. pneumoniae (12.1%), E. coli
      (10.5%), and E. cloacae (7.9%). Pseudomonas aeruginosa isolates had
      susceptibility rates of 67.5% to piperacillin/tazobactam, 59.8% to meropenem,
      57.3% to imipenem. A. baumannii presented susceptibility rates to meropenem of
      89.5%, 88.4% to imipenem, and 74.4% to tobramycin. E. coli and K. pneumoniae were
      fully susceptible to both carbapenems. CONCLUSIONS: Carbapenem resistance among
      Enterobacteriaceae is still rare in this region. A. baumannii and P. aeruginosa
      presented elevated resistance rates to all antimicrobials. Since these two
      bacterial species play an important role in nosocomial infections, the use of
      empirical combination therapy to treat these pathogens may be justified.

PMID- 15947847
TI  - Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) among patients
      visiting the emergency room at a tertiary hospital in Brazil.
AB  - We surveyed patients seen at the emergency room at a tertiary hospital in Brazil
      from August to November 1997. All patients' (n = 600) anterior nares were
      cultured for MRSA; the results were confirmed by oxacillin disk diffusion methods
      and by detection of the mecA gene with PCR. Bacteria were found in 93.3% (560) of
      the patients and MRSA in 0.7% (n = 4). One patient had community-acquired MRSA.
      We concluded that MRSA is uncommon among patients visiting the emergency room.
      The presence of community-acquired MRSA can lead to serious medical and
      epidemiological issues, although initial clinical presentation may not differ
      from that of infections with other staphylococci. The empirical use of vancomycin
      for suspected community-acquired infections is seldom warranted.

PMID- 15947848
TI  - Prevalence of Staphylococcus aureus introduced into intensive care units of a
      University Hospital.
AB  - Staphylococcus aureus is one of the principal human pathogens that colonize
      healthy individuals in the community in general, and it is responsible for severe
      infections in hospitalized patients. Due to an increase in the prevalence of
      strains of methicillin-resistant S. aureus (MRSA), combating these microorganisms
      has become increasingly difficult. A descriptive study was carried out on 231
      patients in intensive care at the Oswaldo Cruz University Hospital (HUOC) in
      Recife, Brazil between January and April 2003 to determine the prevalence of S.
      aureus and MRSA and to evaluate risk factors for colonization by these bacteria
      when introduced into Intensive Care Units (ICUs). Body secretions were collected
      from the nostrils, axillary and perineal regions, and from broken skin lesions,
      of all patients during the first 48 hours following admission to the ICU. Samples
      were inoculated into blood agar and mannitol-salt-agar culture medium and
      identified by Gram staining, and by coagulase, DNAse and agglutination (Slidex
      Staph Test) tests. Growth in Mueller-Hinton agar with 4% sodium chloride and 6
      mg/L oxacillin was used to identify MRSA. In addition, the latex agglutination
      test was performed to identify penicillin-binding protein, PBP 2A. The prevalence
      of S. aureus and MRSA was 87/231 (37.7%) and 30/231 (12.98%), respectively. There
      was no association between any risk factor studied (age, sex, origin of the
      patient--whether hospital or community, previous hospitalization, use of current
      or previous antibiotic therapy, corticotherapy and/or immunotherapy, reason for
      hospitalization and place of hospitalization) and the presence of S. aureus.
      However, a significant association was established between previous
      hospitalization and the presence of MRSA (RR:1.85; CI:1.00-3.41; p=0.041). The
      nostrils were the principal site of colonization by both S. aureus (80.4%) and
      MRSA (26.4%), followed by the perineal area, with rates of 27.6% and 12.6%,
      respectively. If only the nostrils had been investigated, the study would have
      failed to diagnose 17 patients (19.5%) as carriers of the pathogen into the ICU,
      thus contributing towards cross-dissemination.

PMID- 15947849
TI  - Prevalence and factors associated with rectal vancomycin-resistant enterococci
      colonization in two intensive care units in Sao Paulo, Brazil.
AB  - Vancomycin-resistant enterococci (VRE) are important pathogens causing nosocomial
      infections, and there is reason for concern about their resistance and great
      ability to spread in hospital environments, especially intensive-care units
      (ICU). To determine the prevalence of rectal colonization by VRE, and the risk
      factors associated with their presence, rectal surveillance swabs were taken from
      patients under treatment in two intensive-care units (one medical and another
      both medical and surgical) at Sao Paulo Hospital, over a two-year period. Thirty
      three percent of the 147 patients evaluated had VRE. The only significant
      variable in the logistic regression was the length of stay in the ICU.

PMID- 15947850
TI  - Staphylococcus aureus bacteremia: what is the impact of oxacillin resistance on
      mortality?
AB  - In order to analyse the impact of oxacillin resistance on the mortality of
      Staphylococcus aureus bacteremia, and to assess the antimicrobial susceptibility
      of community-acquired strains in two large university hospitals (the Instituto do
      Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao
      Paulo and the Instituto Central do Hospital das Clinicas da Faculdade de Medicina
      da Universidade de Sao Paulo), we carried out a four-month-long prospective
      cohort study, which included 163 consecutive cases of S. aureus bacteremia. Of
      these, 140 (85.9%) were hospital-acquired, 9 (5.5%) were community-acquired and
      14 (8.6%) were of indeterminate origin. No cases of community-acquired infection
      by oxacillin-resistant S. aureus was identified. Among hospital-acquired
      infections, oxacillin-resistant S. aureus was responsible for 64.3% of cases.
      Mortality up to 15 days after diagnosis of bacteremia was 27% (18/67) for
      infections caused by susceptible strains and 33% (32/96) for infections caused by
      oxacillin-resistant strains (p=0.10). The following independent risk factors for
      the acquisition of oxacillin-resistant S. aureus were identified in multiple
      logistical regression analysis: age over 60 years, use of corticoids; presence of
      a central vascular catheter, and previous use of antibiotics.

PMID- 15947851
TI  - Epidemiological and microbiological aspects of acute bacterial diarrhea in
      children from Salvador, Bahia, Brazil.
AB  - In the few cases of acute childhood diarrhea that require antimicrobial therapy,
      the correct choice of the drug depends on detailed previous knowledge of local
      strains. In order to establish such parameters in our city, we reviewed the
      results of all 260 positive stool cultures of children between 0 and 15 years of
      age during two years at a pediatric tertiary care facility in Salvador, Brazil.
      Bacterial strains had been presumptively identified by culturing in selective
      media and by biochemical testing, and their antimicrobial susceptibility patterns
      were automatically detected by the MicroScan Walkaway System. Data about
      patients' sex and age, monthly distribution of the cases, pathogens isolated and
      their antimicrobial resistance patterns were recorded. Males corresponded to
      55.4% of our sample, and most of our patients (42.7%) were between one and four
      years of age. Shigella was the commonest pathogen, being found in 141 (54.3%)
      cultures, while Salmonella was found in 100 (38.4%) cultures and Enteropathogenic
      E. coli in 19 (7.3%). Salmonella was the main causal agent of diarrhea in
      children younger than five years old, whereas Shigella was the most frequent
      pathogen isolated from the stools of children between five and 15 years old. The
      peaks of incidence correspond to the periods of school vacations. Shigella
      specimens presented a very high resistance rate to trimethoprim-sulfamethoxazole
      (90.1%) and to ampicillin (22.0%), while Salmonella presented very low resistance
      rates to all drugs tested. These data are useful for practitioners and they
      reinforce the need for continuous microbiological surveillance.

PMID- 15947852
TI  - Dapsone syndrome with acute renal failure during leprosy treatment: case report.
AB  - Dapsone syndrome is a rare hypersensitivity reaction to dapsone and is
      characterized by high fever, papular or exfoliative dermatitis, progressing to
      liver toxicity and generalized lymphadenopathy, resembling a mononucleosis
      infection. We report a patient who developed acute renal failure, as well as
      other complications characteristic of dapsone syndrome, during leprosy treatment.
      Renal involvement had not been previously described as a dapsone syndrome
      feature.

PMID- 15947853
TI  - Abstracts of the VIII International Symposium on HTLV in Brazil, Sao Paulo,
      Brazil, 16-19 January 2005.

PMID- 15947855
TI  - [National program for asthma control: the possible balance].

PMID- 15947856
TI  - [Airway responsiveness in sarcoidosis].
AB  - The purpose of this study was to measure airway responsiveness in patients with
      sarcoidosis using bronchoprovocation test with methacholine (BPT) in comparison
      to roentgenographic findings, respiratory symptoms, activity and duration of the
      disease. There were 17 patients with Sarcoidosis, 20 asthmatics and 21
      assymptomatics. We used the tidal breathing method with standardizes output for
      the nebulizers. We administered increasing and successively concentrations of
      methacholine beginning with 0.125 to 16 mg/ml. The responses were measured by
      changes in FEV1 or the final concentration was reached. The results were
      expressed as the concentration of methacholine causing 20% fall in FEV1 (PC20).
      Aerosolized bronchodilator was given at the completion of all tests. There were 4
      patients with sarcoidosis who had positive BPT, 3 of them with PC20<8 mg/ml
      associated with respiratory symptoms, bilateral hilar adenopathy, more than two
      year duration and active disease. All the asthmatic subjects had positive BPT
      with CP20<8 mg/ml. The entire assymptomatic group had negative BPT. Positive
      bronchodilator response was reached in 6 patients with sarcoidosis, 20 asthmatics
      and 8 assymptomatic subjects. We concluded that: (a) airway responsiveness can be
      reached in 17.6% patients with sarcoidosis related to bilateral hilar adenopathy,
      chronic and active disease; (b) 50% of sarcoidosis patients with cough and/or
      wheeze had positive BPT, (c) the BPT was able to discriminate asthmatic from
      assymptomatic subjects.

PMID- 15947858
TI  - [Lung cancer--What has changed in two decades].
AB  - Lung cancer (LC) is a major public health problem and it is the most common form
      of cancer in men. It remains the most common cause of cancer death in men and
      women. In the initial decades of the smoking-caused epidemic, squamous cell
      carcinoma was the most frequent type. Recently there was a shift toward
      predominance of adenocarcinoma. The aim of our retrospective study was to compare
      the demographic factors and factors connected with the disease in patients whose
      LC was diagnosed in two distinct periods in H.S. Joao (1979-1982 and 1999-2002).
      A total of 750 LC were diagnosed. Between 1979-1982 a total of 236 patients were
      diagnosed LC (84.3% male; mean age 60.0 +/- 10.0). The most common histological
      type was squamous cell (46.2%). A total of 514 LC were diagnosed during the
      period 1999-2002 (83.9% male; mean age 64.7 +/- 10.8) and adenocarcinoma was the
      most frequent (47.1%). There were significant differences, between the two
      periods analysed concerning smoking (increase in the number of smokers; 73.7% vs
      82.4%), age (increase in the mean age of patients) and histology (higher
      percentage of ade notnocarcinoma and reduction of squamous cell and small-cell
      lung cancer). The percentage of patients treated symptomatically decreased
      significantly in 20 years (26% vs 19%). As a conclusion we can say that there was
      an evolution of histological types in the last two decades and a reduction in the
      number of patients submitted to symptomatic treatment alone.

PMID- 15947857
TI  - [Granzymes A and B in pulmonary sarcoidosis (experimental study)].
AB  - Sarcoidosis is a systemic disease of unknown aetiology, morphologically
      characterized by well-formed epithelioid granulomas, which show little or no
      central necrosis. These may be present in any organ or tissue. The lung is the
      most frequently and prominently involved target. The granuloma is often very
      sharply demarcated from the adjacent tissue and is surrounded by a mantle of
      lymphocytes, which mediate lysis of target cells by various mechanisms, including
      exocytosis of lytic proteins, perforins and granzymes. Sarcoidosis laboratorial
      diagnosis is usually made by SACE and Lisozyme dosages. The granzymes A and B
      could be two other markers of the disease, since the sarcoidosis granuloma is
      rich in cytotoxic and NK cells. An ELISA Kit was used to measure Granzyme A and B
      in serum of a normal control group (NC) (n=30), and in two groups with lung
      pathology: one without sarcoidosis, disease control (DC) (n=21) and other with
      sarcoidosis (S) (n=11). Our results showed that SACE activity is significantly
      augmented in S group comparing with NC and DC, respectively: 82,6+/-32,7/31,9+/
      17,8 - p=0,00017 and 82,6+/-32,7/31,9+/-17,8 - p=0,00024. Lisozyme activity is
      significantly augmented in S and DC groups comparing with NC. Granzyme B showed a
      significant decrease in DC and S groups comparing with NC. Granzyme A showed a
      significant decrease between S/NC groups. Our results suggest that the decrease
      of Granzyme A and B in sarcoidotic patients could be related to an ineffective
      inflammatory local response related to the formation of sarcoidosis granulomas.
      More studies are needed, particularly in BAL.

PMID- 15947859
TI  - [Idiophatic mediastinal fibrosis: a case report].
AB  - We herein report a case of a male patient, who presented a mediastinal mass that
      had a slow growth over the years. After surgery, that made the diagnosis of
      idiopathic mediastinal fibrosis, the growth stabilized. Four years latter it was
      observed a substantial increase which lead to the inevitable compression of vital
      structures which, in turn, led to pulmonary hypertension. Idiopathic mediastinal
      fibrosis is an extremely rare pathology. There are same cases in which it is
      associated with other pathologies but has always a fatal prognosis when surgery
      is not an option.

PMID- 15947860
TI  - [Legionella pneumonia--a case report].
AB  - Legionella, as a cause of community-acquired pneumonia, is probably under
      recognized because the diagnosis relies on the use of specific tests as well the
      existence of an in-numerous species and serogroups not easily identify by the
      tests available. In studies from Europe and North America, it ranged from 2 to 15
      percent of all community-acquired pneumonias that required hospitalisation, in
      the first four causes when culture methods were done and the second cause of
      those admitted in the intensive care units. We do a case report of 43 year-old
      man with history of cigarette smoking and corticosteroid therapy for a ocular
      disease, that presents with a pneumonia complicated with a Acute Respiratory
      Distress Syndrome (ARDS), that leaded to his admission to an intensive care unit
      were he was mechanical ventilated. The epidemiological investigation identified
      Legionella pneumophila serogroup 1. The authors present this case doing a brief
      review of this disease and discussing the epidemiology, clinical features,
      laboratory diagnosis as well as therapeutic options.

PMID- 15947861
TI  - The discriminative ability of peripheral and axial bone measurements to identify
      proximal femoral, vertebral, distal forearm and proximal humeral fractures: a
      case control study.
AB  - Previous studies evaluating peripheral bone measurement devices have often used
      discontinued technologies, compared single devices, only evaluated a single
      fracture syndrome or failed to make a comparison with central densitometry, which
      is currently the gold standard for fracture discrimination. We have used a case
      control study to evaluate the ability of different peripheral and central bone
      techniques to discriminate between fracture cases and controls, determine the
      impact of different measurement sites, evaluate the role of measuring the
      cortical or trabecular envelopes using quantitative computed tomography (QCT) and
      determine the impact of using combinations of sites and techniques on fracture
      discrimination. We recruited postmenopausal women with proximal femoral (n=53),
      vertebral (n=73), distal forearm (n=78) or proximal humeral (n=75) fractures, and
      500 population-based women (age 55-80 years). All subjects had measurements of
      the spine, total hip and distal forearm with dual-energy X-ray absorptiometry
      (DXA), distal forearm QCT and quantitative ultrasound (QUS) of the heel (four
      devices), finger (two devices), radius and metatarsal. The association of each
      device with fracture was expressed as the age-adjusted standardized odds ratios
      (sOR) per 1-SD decrease of population variance. The association of bone
      measurements with fracture was site-specific. We found the hip (sOR up to 3.40)
      and vertebral (sOR up to 4.67) fractures were more closely associated with
      central bone measurements than upper limb fractures (sOR 1.96 and 2.05). The
      performance of heel broadband ultrasound attenuation (sOR 2.09-2.41), heel speed
      of sound (sOR 1.79-2.28) and peripheral BMD (sOR 2.07 and 2.24) was comparable
      with total hip (sOR 2.46) and lumbar spine DXA (sOR 2.31) in discriminating all
      types of osteoporotic fracture. In general, measuring cortical or trabecular
      envelopes did not increase sOR. However, combining different measurement sites or
      technologies provided additional information, which was independent of total hip
      BMD. The ability of different bone measurements to discriminate between fracture
      cases and controls is device- and site-specific, with additional information
      obtained by combining measurement sites and technologies.

PMID- 15947863
TI  - Metacarpal index and bone mineral density in healthy African-American women.
AB  - Bone mineral density (BMD) reference data of non-Caucasian women is scarce but
      greatly needed for African-American women. The objective of this study was to
      establish a metacarpal normative reference database for African-American women
      using digital X-ray radiogrammetry (DXR) and hand radiographs and compare these
      values to existing Caucasian data. Two hundred and fifty healthy African-American
      women between the ages of 20 and 79 years old, 14 of whom were excluded, were
      recruited to participate from four different clinical sites. The study population
      was recruited in approximately equal number into the following groups: 20-29, 30
      39, 40-49, 50-59, 60-69 and 70-79 years of age. A radiograph was acquired of each
      subject's non-dominant hand. The radiographs were scanned and analyzed using
      radiogrammetric techniques, and the BMD, MCI (Metacarpal Index), bone width and
      cortical thickness were calculated. The regression curve that best fit the data
      was a second order polynomial. The BMD and MCI of young adult women (20-40 years
      of age) were used to calculate T-score parameters. The young reference BMD and
      MCI with their associated standard deviations were found to be 0.6045 g/cm2+/
      0.0529 g/cm2 and 0.5096 and 0.0792, respectively. However, the MCI was found to
      be approximately 2.5% lower (-0.0118) compared to Caucasian women. The African
      American metacarpal BMD was found to be 3.5% (0.0207 g/cm2) higher across all
      ages when compared to existing Caucasian reference data acquired in a similar
      way. The differences were found to be entirely due to larger bone size, cortical
      diameter and bone width in the African-American women.

PMID- 15947862
TI  - Influence of ultraviolet radiation on the production of 25 hydroxyvitamin D in
      the elderly population in the city of Sao Paulo (23 degrees 34'S), Brazil.
AB  - The lack of vitamin D is a major changeable factor involved in the
      pathophysiology of osteoporosis. Since the major source for this hormone is its
      cutaneous synthesis via ultraviolet radiation (UVR), we studied the serum level
      of 25-hydroxyvitamin D (25OHD) in 250 free-living elderly people (79.1 years old)
      from a subtropical region according to the UVR incidence and its correlations
      with parathormone (PTH) and ionized calcium. UVR and 25OHD differed according to
      the season of the year (P<0.001), with greater radiation in the summer and less
      in the winter, whereas the 25OHD peak and nadir occurred in autumn and spring,
      respectively. The highest 25OHD mean was 67.2 nmol/l, and the lowest was 29.1
      nmol/l corresponding, respectively, to the measure of the month subsequent to the
      one of most and least sunlight incidence. Clustered by season, the correlation
      between UVR and 25OHD for the following seasons was r=0.98 and between the PTH
      and 25OHD of corresponding seasons, r=-0.95. Vitamin D deficiency occurred in
      15.4% of patients, insufficiency in 41.9% and secondary hyperparathyroidism in
      55%. In conclusion, we found a seasonal variation in 25OHD levels that strongly
      correlated with the PTH levels when separated by the seasons of the year. The
      25OHD levels correlated with the UVR of the previous quarter, requiring no less
      than 30 days for serum changes arising from exposure to or deprivation of UVR to
      be observed. The prevalence of vitamin D deficiency/insufficiency found was
      greater than expected, even when compared to countries exposed to less solar
      irradiation. Thus, measures to encourage greater sun exposure and food enrichment
      policies should also be considered.

PMID- 15947864
TI  - Dissemination and survival of non-indigenous bacterial genomes in pristine
      Antarctic environments.
AB  - Continental Antarctic is perceived as a largely pristine environment, although
      certain localized regions (e.g., parts of the Ross Dependency Dry Valleys) are
      relatively heavy impacted by human activities. The procedures imposed on
      Antarctic field parties for the handling and disposal of both solid and liquid
      wastes are designed to minimise eutrofication and contamination (particularly by
      human enteric bacteria). However, little consideration has been given to the
      significance, if any, of less obvious forms of microbial contamination resulting
      from periodic human activities in Antarctica. The predominant commensal
      microorganism on human skin, Staphylococcus epidermidis, could be detected by
      PCR, in Dry Valley mineral soils collected from heavily impacted areas, but could
      not be detected in Dry Valley mineral soils collected from low impact and
      pristine areas. Cell viability of this non-enteric human commensal is rapidly
      lost in Dry Valley mineral soil. However, S. epidermidis can persist for long
      periods in Dry Valley mineral soil as non-viable cells and/or naked DNA.

PMID- 15947865
TI  - AMP-forming acetyl-CoA synthetase from the extremely halophilic archaeon
      Haloarcula marismortui: purification, identification and expression of the
      encoding gene, and phylogenetic affiliation.
AB  - Halophilic archaea activate acetate via an (acetate)-inducible AMP-forming acetyl
      CoA synthetase (ACS), (Acetate+ATP+CoA --> Acetyl-CoA+AMP+PP(i)). The enzyme from
      Haloarcula marismortui was purified to homogeneity. It constitutes a 72-kDa
      monomer and exhibited a temperature optimum of 41 degrees C and a pH optimum of
      7.5. For optimal activity, concentrations between 1 M and 1.5 M KCl were
      required, whereas NaCl had no effect. The enzyme was specific for acetate (100%)
      additionally accepting only propionate (30%) as substrate. The kinetic constants
      were determined in both directions of the reaction at 37 degrees C. Using the N
      terminal amino acid sequence an open reading frame - coding for a 74 kDa protein 
      was identified in the partially sequenced genome of H. marismortui. The function
      of the ORF as acs gene was proven by functional overexpression in Escherichia
      coli. The recombinant enzyme was reactivated from inclusion bodies, following
      solubilization in urea and refolding in the presence of salts, reduced and
      oxidized glutathione and substrates. Refolding was dependent on salt
      concentrations of at least 2 M KCl. The recombinant enzyme showed almost
      identical molecular and catalytic properties as the native enzyme. Sequence
      comparison of the Haloarcula ACS indicate high similarity to characterized ACSs
      from bacteria and eukarya and the archaeon Methanosaeta. Phylogenetic analysis of
      ACS sequences from all three domains revealed a distinct archaeal cluster
      suggesting monophyletic origin of archaeal ACS.

PMID- 15947866
TI  - A diversity of bacteriophage forms and genomes can be isolated from the surface
      sands of the Sahara Desert.
AB  - The surface sands of the Sahara Desert are exposed to extremes of ultraviolet
      light irradiation, desiccation and temperature variation. Nonetheless, the
      presence of bacteria has recently been demonstrated in this environment by
      cultivation methods and by 16S rDNA analyses from total DNA isolated from surface
      sands. To discern the presence of bacteriophages in this harsh environment, we
      searched for extracellular phages and intracellularly located phages present as
      prophages or within pseudolysogens. Mild sonication of the sand, in different
      liquid culture media, incubated with and without Mitomycin-C, was followed by
      differential centrifugation to enrich for dsDNA phages. The resulting
      preparations, examined by electron microscopy, revealed the presence of virus
      like particles with a diversity of morphotypes representative of all three major
      double-stranded DNA bacteriophage families (Myoviridae, Siphoviridae and
      Podoviridae). Moreover, pulsed-field gel electrophoresis of DNA, extracted from
      the enriched bacteriophage preparations, revealed the presence of distinct bands
      suggesting the presence of putative dsDNA phage genomes ranging in size from 45
      kb to 270 kb. Characterization of the bacteriophages present in the surface sands
      of the Sahara Desert extends the range of environments from which bacteriophages
      can be isolated, and provides an important point of departure for the study of
      phages in extreme terrestrial environments.

PMID- 15947867
TI  - Is preoperative lymphoscintigraphy needed for sentinel node procedures in breast
      cancer?

PMID- 15947868
TI  - Antitumor vaccines: of mice and men?

PMID- 15947871
TI  - An analysis of risk factors for cutaneous melanoma by anatomical site
      (Australia).
AB  - OBJECTIVE: Emerging evidence suggests that melanomas arising on the head and neck
      that are not lentigo maligna melanomas have different associations with
      phenotypic and environmental risk factors than those on the trunk and other
      sites. We sought to test this hypothesis in a population-based study in
      Queensland, Australia. METHODS: Risk factor data were collected from 2360
      participants with incident cutaneous melanoma diagnosed 1982--1990, including 167
      participants with lentigo maligna melanoma. For each risk factor, polytomous
      logistic regression analysis, using the trunk as a reference category, was used
      to estimate the odds ratio and 95% confidence interval for cutaneous melanomas by
      anatomical site. RESULTS: Participants with melanomas of the head and neck were
      significantly older than those with melanomas of the trunk (males 52.7 versus
      49.7 years; females 47.8 versus 40.5 years). Compared with patients with truncal
      melanomas, those of the head and neck were less likely to have many nevi (OR
      0.41, 95% CI 0.13--1.31), although this did not reach statistical significance.
      Among females, melanomas of the lower limb were negatively associated with a past
      history of non-melanoma skin cancer (OR 0.41, 95% CI 0.23-0.74). CONCLUSIONS: We
      have observed heterogeneity for melanoma risk by anatomical site, lending weight
      to the hypothesis that cutaneous melanomas may develop through multiple causal
      pathways.

PMID- 15947872
TI  - Hereditary colorectal cancer syndromes.
AB  - The purpose of this article is to review the genetic colorectal cancer syndromes
      including Hereditary Nonpolyposis Colorectal Cancer (HNPCC), Family Polyposis
      (FAP) and the hamartomatous polyposis syndromes. HNPCC is the most common of the
      hereditary colorectal cancer syndromes, and is the result of defects in the
      mismatch repair genes. Individuals with HNPCC have an 80 lifetime risk of
      colorectal cancer, and in females a 30-50% risk of endometrial cancer, as well as
      predisposition for a number of other malignancies. Early screening and interval
      surveillance for colorectal and endometrial cancer are recommended. In FAP,
      mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene give rise
      to hundreds to thousands of colorectal polyps, some of which will inevitably
      progress to cancer. Early diagnosis and timely prophylactic colectomy prevent
      this outcome. Chemoprevention with nonsteroidal anti-inflammatory drugs can
      reduce adenoma number and size in FAP, but the effect is incomplete. In addtion,
      surveillance for upper gastrointestinal tract malignancies is necessary.
      Attenuated forms of FAP may be the result of mutations in the APC gene, or in the
      recently described MYH gene. Mutations in the MYH gene should be considered in
      individuals with multiple adenomas whose family history does not reflect an
      autosomal dominant pattern of inheritance. The hamartomatous polyposis syndromes
      are uncommon but distinctive disorders in which multiple hamartomatous polyps
      develop at a young age. Our understanding of the genetic basis of these disorders
      is improving, and a predisposition for gastrointestinal and other malignancies
      has recently been recognized. This article summarizes the genetics, clinical
      manifestations and clinical management of each of these syndromes with an
      emphasis on genetic testing and prevention.

PMID- 15947873
TI  - Early life events and later risk of colorectal cancer: age-period-cohort
      modelling in the Nordic countries and Estonia.
AB  - BACKGROUND: A lowering of colorectal cancer risk for the birth cohorts born
      around World War II (WWII) has previously been observed in Norway, a country
      which suffered some 20% caloric restriction during the war. The purpose of the
      study was to conduct a similar kind of analysis in the other Nordic countries and
      Estonia, which were also subjected to various degrees of energy restriction
      during WWII. METHODS: All new cases of colorectal cancer in the Nordic countries
      and Estonia diagnosed between 40 and 84 years of age and born between 1874 and
      1953, were collected from the national cancer registries. The incidence data were
      fitted to an age-period-cohort model. RESULTS: A transient drop in the estimated
      colorectal cancer incidence rate was observed for the birth cohorts born around
      WWII in Estonia, together with a tendency of decreased risk in Sweden and
      Denmark. CONCLUSION: The previously observed lowering of colorectal cancer risk
      for persons born during WWII in Norway also prevails in Estonia. Energy
      restriction is a possible explanation for these findings, since the countries
      suffered from varying nutritional conditions during the war. Exogenous factors
      acting during periods early in life may have an impact on later colorectal cancer
      risk.

PMID- 15947874
TI  - Dietary intakes of fruit, vegetables, and fiber, and risk of colorectal cancer in
      a prospective cohort of women (United States).
AB  - OBJECTIVE: Although animal studies suggest an inverse association between
      consumption of plant foods and risk of colorectal cancer, many observational data
      have failed to support such an association. We prospectively examined the
      association between dietary intakes of fruit, vegetables, and fiber and
      colorectal cancer risk in a large female cohort from the Women's Health Study.
      METHODS: Among 39,876 healthy women aged >/=45 years at baseline, 36,976 with
      baseline self-reported information on dietary intakes and other risk factors for
      colorectal cancer were included in the analyses. During an average follow-up of
      10 years, 223 women were diagnosed with colorectal cancer. Intakes of fruit,
      vegetables, and fiber were assessed by a baseline food-frequency questionnaire.
      The analyses were carried out using the Cox proportional hazards regression and
      all tests were two-sided. RESULTS: Intakes of fruit, vegetables, and the specific
      subgroups were not found to be associated with colorectal cancer risk.
      Multivariate relative risks (RRs) comparing the highest with lowest quintile were
      0.79 (95% CI=0.49-1.27,p for trend =0.30) for fruit intake, and 0.88 (95% CI=0.56
      1.38,p for trend=0.30) for vegetables intake. Similarly, intake of total fiber
      was not associated with colorectal cancer risk; the RR for the highest relative
      to lowest quintile was 0.75 (95% CI=0.48-1.17,p for trend=0.12). However, higher
      intake of legume fiber was associated with a lower risk of colorectal cancer; the
      RR for the highest versus slowest quintile was 0.60 (95% CI=0.40-0.91,p for
      trend=0.02). CONCLUSIONS: Our data offer little support for associations between
      intakes of fruit, vegetables, and fiber, and colorectal cancer risk. However, our
      data suggest that legume fiber and/or other related sources may reduce risk of
      colorectal cancer.

PMID- 15947875
TI  - The impact of reproductive factors on breast cancer risk--the feasibility of
      using Swedish population-based registers to account for the effect of confounding
      in cohort studies.
AB  - OBJECTIVE: The aim of this study was to analyze the impact of reproductive
      factors on breast cancer risk among Swedish women by using nationwide population
      registers. METHODS: A cohort including all Swedish women born between 1920 and
      1959 was followed up to 1997 by record linkage to different population-based
      registers. More than 4 million children were linked to the women in the cohort
      and 60,328 women were diagnosed with breast cancer. Poisson regression was used
      to model the breast cancer incidence by risk groups. In a sub-cohort of 18,164
      women irradiated for skin hemangioma in infancy, the breast cancer risk was
      analyzed in relation to radiation dose and accounting for reproductive factors.
      RESULTS: The relative breast cancer risk (RR) for the reproductive factors was
      0.35 [ 95% confidence interval (CI) 0.30--0.42] for women with 6 or more children
      and the first child before the age of 20 years, and RR was 1.11 (95% CI 1.06-
      1.18) for uniparous women with the first child at age 35 years or older, compared
      to nulliparous women. The discrepancies of reproductive factors in the hemangioma
      cohort compared to Swedish women had a minor effect on RR, with a reduction from
      1.13 (95%CI 1.00--1.26) to 1.11 (95% CI 0.99--1.25). CONCLUSIONS: This study
      shows the feasibility of using population-based registers to retrieve reliable
      information on reproductive factors to eliminate its confounding effect when
      analyzing other risk factors.

PMID- 15947876
TI  - Are risk factors for breast cancer associated with follow-up procedures in
      diverse women with abnormal mammography?
AB  - OBJECTIVE: We evaluated the association of risk factors for breast cancer with
      reported follow-up procedures after abnormal mammography among diverse women.
      METHODS: Women ages 40--80 years were recruited from four clinical sites after
      receiving a screening mammography result that was classified as abnormal but
      probably benign, suspicious or highly suspicious, or indeterminate using standard
      criteria. A telephone-administered survey asked about breast cancer risk factors
      (family history, estrogen use, physical inactivity, age of menarche, age at birth
      of first child, parity, alcohol use), and self-reported use of diagnostic tests
      (follow-up mammogram, breast ultrasound, or biopsy). RESULTS: Nine hundred and
      seventy women completed the interview, mean age was 56, 42% were White, 19%
      Latina, 25% African American, and 15% Asian. White women were more likely to have
      a positive family history (20%), use estrogen (32%), be nulliparous (17%) and
      drink alcohol (62%). Latinas were more likely to be physically inactive (93%),
      African Americans to have early onset of menarche (53%) and Asians first child
      after age 30 (21%). White women were more likely to have suspicious mammograms
      (40%) and to undergo biopsy (45%). In multivariate models, Latinas were more
      likely to report breast ultrasound, physical inactive women reported fewer follow
      up mammograms, and care outside the academic health center was associated with
      fewer biopsies. Indeterminate and suspicious mammography interpretations were
      significantly associated with more biopsy procedures (OR=8.4; 95% CI=3.8-18.5 and
      OR=59; 95% CI=35-100, respectively). CONCLUSIONS: Demographic profile and breast
      cancer risk factors have little effect on self-reported use of diagnostic
      procedures following an abnormal mammography examination. Level of mammography
      abnormality determines diagnostic evaluation but variance by site of care was
      observed.

PMID- 15947878
TI  - Sexually transmitted diseases and other urogenital conditions as risk factors for
      prostate cancer: a case--control study in Wayne County, Michigan.
AB  - OBJECTIVE To investigate associations between prostate cancer and sexually
      transmitted diseases (STDs), prostatitis, benign prostatic hyperplasia (BPH), and
      vasectomy in a population-based case-control study in Wayne County, Michigan,
      among African American and white men aged 50--74 years. METHODS: Incident
      prostate cancer cases (n=700) from 1996--1998 were identified from the
      Metropolitan Detroit Cancer Surveillance System. Controls (n=604) were identified
      through random digit dialing and Medicare recipient lists, and frequency matched
      to cases on age and race. History of potential prostate cancer risk factors was
      ascertained through in-person interview. RESULTS: Prostate cancer was not
      associated with STD or vasectomy history. History of prostatitis was associated
      with prostate cancer among all subjects (odds ratio [OR]=1.8, 95% confidence
      interval [CI]: 1.1, 2.9) and in African American men (OR=2.2, 95% CI: 1.1, 4.6).
      History of BPH was associated with prostate cancer among all subjects (OR=2.4,
      95% CI: 1.8, 3.3); significant associations were observed in both African
      American (OR=2.7, 95% CI: 1.6, 4.4) and white (OR=2.3, 95% CI: 1.5, 3.4) men.
      CONCLUSIONS: Among all subjects, prostate cancer was associated with prostatitis
      and BPH history, but not with STD or vasectomy history. Prevention efforts could
      be enhanced if inflammatory or infectious etiologies are found to be of
      importance in the subsequent development of prostate cancer.

PMID- 15947877
TI  - Plasma insulin-like growth factor-1 and binding protein-3 and subsequent risk of
      prostate cancer in the PSA era.
AB  - OBJECTIVE: The insulin-like growth factor (IGF) axis is thought to contribute to
      the growth and progression of prostate cancer. Some prospective studies support a
      direct association between IGF-1 and prostate cancer, in particular advanced
      disease, whereas both inverse and direct associations with prostate cancer have
      been reported for insulin-like growth factor binding protein-3 (IGFBP-3), the
      major IGF-1 binding protein in circulation. We prospectively investigated the
      associations of plasma IGF-1 and IGFBP-3 concentrations with prostate cancer
      detected in the PSA era. METHODS: We identified 462 prostate cancer cases
      diagnosed after providing a blood specimen in 1993, but before January 1998 among
      men in the Health Professionals Follow-up Study. Controls were 462 age-matched
      men without prostate cancer who had had a PSA test after providing a blood
      specimen. We measured plasma concentrations of IGF-1 and IGFBP-3 by ELISA.
      Conditional logistic regression was used to estimate odds ratios (OR) and 95%
      confidence intervals (CI) of prostate cancer. RESULTS: Men with higher
      concentrations of IGF-1 (comparing extreme quartiles OR=1.37, 95% CI 0.92-2.03, p
      trend=0.05) and IGFBP-3 (OR=1.62, 95% CI 1.07-2.46, p-trend=0.08) had a higher
      risk of prostate cancer. After mutual statistical adjustment, these associations
      were attenuated for both IGF-1 (OR=1.17, 95% CI 0.69-1.99, p-trend=0.29) and
      IGFBP-3 (OR=1.40, 95% CI 0.80-2.44, p-trend=0.56). We found no significant
      association of IGF-1 with regionally invasive or metastatic (>/=T3b, N1, or M1)
      prostate cancer, although the number of these cases was small (n=42).
      CONCLUSIONS: Our findings for IGF-1 and prostate cancer diagnosed in the PSA era
      are similar to most previous studies, albeit weaker in magnitude. Our suggestive
      positive findings for IGFBP-3 are similar to some studies, but in direct contrast
      to others.

PMID- 15947879
TI  - Alcohol drinking and risk of localized versus advanced and sporadic versus
      familial prostate cancer in Sweden.
AB  - BACKGROUND: It is unknown whether the association of alcohol consumption with
      prostate cancer risk varies between localized and advanced cases, or between
      sporadic and familial cases. METHODS: We assessed recent alcohol drinking in a
      population-based case--control study of Swedish men, including 1499 cases and
      1130 controls. Drinking status and average volume, frequency, and type of alcohol
      consumed were evaluated. Unconditional logistic regression was performed to
      estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs)
      for associations between alcohol consumption and prostate cancer risk. RESULTS:
      Prostate cancer cases were more likely than controls to be current or former,
      rather than never, drinkers. However, there was no association between recent
      total alcohol, beer, wine, and liquor consumption and risk of overall prostate
      cancer, nor advanced, sporadic, or familial prostate cancer. The OR for risk of
      overall disease among men who drank more than 135 g of total alcohol per week
      versus non-drinkers was 1.2 (95% CI: 0.9, 1.5), p(trend)=0.12. There was a
      marginal positive association between alcohol intake and risk of localized
      disease. CONCLUSIONS: We detected no association between recent alcohol
      consumption and risk of advanced, sporadic, or familial prostate cancer, and a
      borderline positive association with localized disease.

PMID- 15947880
TI  - Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and
      gastric non-cardia adenocarcinoma among men and women in a nested case-control
      study.
AB  - OBJECTIVES: To prospectively assess the influence of body mass index (BMI),
      tobacco, and alcohol on the occurrence of esophageal, gastric cardia, and non
      cardia gastric adenocarcinoma, and to detect any sex differences that could
      explain the male predominance of these tumors. METHODS: A case-control study
      nested in the General Practitioner Research Database in the United Kingdom, 1994-
      2001. Odds ratios (ORs) were calculated with 95% confidence intervals (CI),
      including multivariate analysis. RESULTS: During follow-up of 4,340,207 person
      years, we identified 287 esophageal adenocarcinomas, 195 gastric cardia
      adenocarcinomas, 327 gastric non-cardia adenocarcinomas, and 10,000 controls. A
      positive association was found between overweight (BMI > 25 kg/m(2)) and
      esophageal adenocarcinoma (OR 1.67, 95% CI 1.22--2.30), and gastric cardia
      adenocarcinoma (OR 1.46, 95% CI 0.98--2.18), but not non-cardia gastric
      adenocarcinoma. The association between BMI and esophageal and gastric cardia
      adenocarcinoma were dose-dependent and seemingly independent of reflux. No strong
      sex differences were identified. Smokers, particularly females, were at increased
      risk of all studied adenocarcinomas, while no association with alcohol was found.
      CONCLUSIONS: Overweight increases risk of esophageal and gastric cardia
      adenocarcinoma, while tobacco smoking increases risk of esophageal, gastric
      cardia, and non-cardia gastric adenocarcinoma. The male predominance is not
      explained by sex differences in risk factor profiles of the studied exposures.

PMID- 15947881
TI  - Fertility patterns prior to testicular cancer diagnosis.
AB  - Although prenatal factors are associated with testicular cancer etiology, few
      studies have examined the reproductive profiles of men prior to diagnosis. This
      case--control study investigated fertility patterns prior to testicular cancer
      diagnosis by comparing pregnancies fathered by 201 men with testicular cancer and
      those fathered by 204 age- and neighborhood-matched controls. Regardless of
      histology, men with testicular cancer were less likely to have ever fathered a
      live-born infant (OR 0.67, 95% CI 0.42--1.06) and had fewer offspring than
      control men (means 1.8 and 2.1, respectively). Cases were more likely than
      controls to report having an infertility diagnosis (OR 9.47, 95% CI 1.19--75.2)
      or a low sperm count (OR 5.85, 95% CI 1.28--26.7) prior to cancer diagnosis. No
      differences were observed for pregnancy loss. These results indicate that men
      with testicular cancer may have impaired fecundity and fertility as evidenced by
      an infertility diagnosis or low sperm count and fewer live births. Further
      research is needed to determine the extent to which reproductive factors are
      involved in the etiology of testicular cancer.

PMID- 15947882
TI  - Regular use of aspirin or acetaminophen and risk of non-Hodgkin lymphoma.
AB  - Regular use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)
      has been hypothesized to be associated with reduced risk of non-Hodgkin lymphoma
      (NHL), although previous results have been inconsistent. The current study
      investigated the effects of regular aspirin or acetaminophen use on non-Hodgkin
      lymphoma risk among 625 individuals with primary, incident NHL and 2512 age and
      sex matched hospital controls with non-neoplastic conditions who completed a
      comprehensive epidemiologic questionnaire. Results indicate that regular aspirin
      use may be associated with decreased NHL risk among men [adjusted odds ratio
      (aOR) 0.82, 95% confidence interval (CI), 0.65--1.04], but not among women (aOR
      0.93, 95% CI, 0.71--1.23). In contrast, regular acetaminophen use was associated
      with elevated NHL risk among women (aOR 1.71, 95% CI, 1.18--2.50) but not among
      men (aOR 0.75, 95% CI, 0.48--1.17). Other studies have demonstrated that
      acetaminophen is associated with transient decreases in DNA repair, and
      lymphocytes may be particularly susceptible to DNA damage, suggesting a mechanism
      for the elevated NHL risk observed.

PMID- 15947883
TI  - Cancer incidence patterns among adolescents and young adults in the United
      States.
AB  - OBJECTIVE: The purpose of this study was to examine age-specific cancer incidence
      patterns among adolescents and young adults (ages 15--49). METHOD: Cancer
      incidence data for 1995--1999 from 22 population-based central cancer registries,
      covering about 47% of the US population, were used. Relative frequencies and
      average annual age-specific incidence rates per 100,000 person-year were computed
      for the five-year age groups from age 15--19 years through 45--49 years. Tests of
      significance for comparison were at a level of p<0.05. RESULTS: The age at
      crossover from a predominance of non-epithelial cancers to a predominance of
      epithelial cancers during adolescence and young adulthood varied by gender and
      race. Epithelial cancer became the predominant type of tumor after age 40 years
      among males while it was the predominant type after age 25 years among females.
      There was also a shift in the top five cancer types with increasing age, which
      varied by race and gender. Epithelial cancers of the thyroid, breast, ovary, and
      cervix uteri started to increase sharply among young women in their 20s while
      among males epithelial cancers rarely occurred until the early 30s (ages 30--34).
      Cancers of the female breast, colon and rectum, and lung began to occur at an
      earlier age and increased more sharply among blacks than among whites. However,
      the incidence rates of epithelial thyroid and ovarian cancers rose more quickly
      among whites than blacks. Non-Hodgkin lymphoma and soft tissue sarcoma (excluded
      Kaposi's sarcoma) increased with age among both whites and blacks but the rates
      were significantly higher among blacks than among whites. Both Kaposi's sarcoma
      and testicular cancer incidence increased with age and peaked in the early 30s
      (ages 30--34). The former was significantly higher among blacks than whites while
      the latter was significantly higher among whites than blacks. Cervical cancer
      incidence leveled off when white women reached their 30s, but for black women the
      rate continued to rise with advancing age. Cutaneous melanoma rates were
      significantly higher among females than among males between the ages of 15 and
      39. Conclusion Cancer incidence patterns among adolescents and young adults are
      distinctive. Specific cancer prevention and control strategies should be targeted
      accordingly and tailored to their specific needs.

PMID- 15947884
TI  - Cancer in Indigenous people of New South Wales--a response to: cancer in
      Indigenous Australians: a review.

PMID- 15947885
TI  - Aldosterone and heart failure: the rest of the story.

PMID- 15947886
TI  - Aldosterone biosynthesis, regulation, and classical mechanism of action.
AB  - Circulating aldosterone is principally made in the glomerulosa zone of the
      adrenal cortex by a series of enzyme steps leading to the conversion of
      cholesterol to aldosterone. Uniquely, aldosterone's production is regulated at
      two critical enzyme steps: (1) early in its biosynthetic pathway (the conversion
      of cholesterol to pregnenolone cholesterol side chain cleavage enzyme) and (2)
      late (the conversion of corticosterone to aldosterone by aldosterone synthase). A
      variety of factors modify aldosterone secretion--the most important are
      angiotensin II (AngII), the end-product of the renin-angiotensin system (RAS),
      and potassium. However ACTH, neural mediators and natriuretic factors also
      contribute at least over the short run. Aldosterone's classical epithelial effect
      is to increase the transport of sodium across the cell in exchange for potassium
      and hydrogen ions. Although still controversial, there is an increasing body of
      data that supports the hypothesis that aldosterone can be synthesized in tissues
      outside of the adrenal cortex, specifically in the heart and the vasculature.
      Aldosterone's biosynthesis appears to be regulated in these tissues similar to
      what occurs in the adrenal cortex. The role of this extra adrenal aldosterone
      production in health and disease is as of yet undetermined.

PMID- 15947887
TI  - Mineralocorticoid receptors: distribution and activation.
AB  - Mineralocorticoid receptors (MR) bind both mineralocorticoids and glucocorticoids
      with high affinity (deoxycorticosterone = corticosterone >/= aldosterone =
      cortisol), and are found in both Na(+) transporting epithelia (e.g. kidney,
      colon) and nonepithelial tissues (e.g. heart, brain). MR evolved before
      aldosterone synthase, consistent with their acting in nonepithelial tissues as
      high affinity glucocorticoid receptors, essentially always occupied by normal
      levels of endogenous glucocorticoids. In epithelial tissues the enzyme 11beta
      hydroxysteroid dehydrogenase Type 2 (11betaHSD2) allows aldosterone to
      selectively activate MR, by converting cortisol to cortisone and NAD to NADH.
      11betaHSD2 debulks intracellular cortisol by 90%, to levels approximately 10-fold
      those of aldosterone, so that when the enzyme is operating most epithelial MR are
      occupied but not activated by cortisol. When intracellular redox state is changed
      by inhibition of 11beta HSD2, generation of reactive oxygen species, or
      intracellular introduction of oxidised glutathione (GSSG)-cortisol changes from
      an MR antagonist to an MR agonist. This bivalent activity of cortisol appears to
      underlie the therapeutic efficacy of MR blockade in heart failure (RALES,
      EPHESUS) and in essential hypertension, providing a rationale for MR blockade in
      cardiovascular disease not characterized by elevated aldosterone levels. Its
      wider (patho)physiologic implications, particularly for neurobiology, remain to
      be explored.

PMID- 15947889
TI  - Effect of aldosterone and mineralocorticoid receptor blockade on vascular
      inflammation.
AB  - Aldosterone, the final product of the renin-angiotensin-aldosterone system, is
      classically viewed as a regulator of renal sodium and potassium handling, blood
      volume, and blood pressure. Recent studies suggest that aldosterone can cause
      microvascular damage, vascular inflammation, oxidative stress and endothelial
      dysfunction. In animal models, aldosterone-mediated vascular injury in the brain,
      heart, and kidneys leads to stroke, myocardial injury, and proteinuria. These
      effects may be modified by dietary salt intake; aldosterone-mediated vascular
      damage is increased in susceptible animals fed a high-salt diet compared to a low
      salt diet despite lower plasma aldosterone levels on the high-salt diet. In
      humans, there is a growing literature supporting the adverse effects of
      aldosterone in heart failure, hypertension, left ventricular hypertrophy, and
      renal disease. Aldosterone receptor antagonists are beneficial even in patients
      on angiotensin converting enzyme inhibitors and attenuate aldosterone-mediated
      vascular injury by mechanisms that appear to be independent of changes in
      systolic blood pressure. This review focuses on the adverse effects of
      aldosterone on the vascular system and describes our current understanding of the
      underlying mechanisms for this injury.

PMID- 15947888
TI  - Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and
      their effects on potassium homeostasis.
AB  - Spironolacotone and eplerenone are mineralocorticoid-blocking agents used for
      their ability to block both the epithelial and non-epithelial actions of
      aldosterone. Spironolactone is a non-selective mineralocorticoid receptor
      antagonist with moderate affinity for both progesterone and androgen receptors.
      The latter property increases the likelihood of endocrine side effects with
      spironolactone including loss of libido, menstrual irregularities, gynecomastia
      and impotence. Eplerenone is a next generation aldosterone receptor antagonist
      selective for aldosterone receptors alone. This lesser affinity for progesterone
      and androgen receptors was arrived at by replacing the 17-alpha -thioacetyl group
      of spironolactone with a carbomethoxy group. Eplerenone is further distinguished
      from spironolactone by its shorter half-life and the fact that it does not have
      any active metabolites. Both eplerenone and spironolactone are effective
      antihypertensive agents and each has been shown to improve the morbidity and
      mortality of heart failure. Eplerenone or spironolactone use can increase serum
      potassium values and occasionally results in clinically relevant hyperkalemia.
      This is more apt to occur with spironolactone due to the very long half-life of
      several of its active metabolites.

PMID- 15947890
TI  - Effects of aldosterone and mineralocorticoid receptor blockade on intracellular
      electrolytes.
AB  - Genomic mechanisms of mineralocorticoid action have been increasingly elucidated
      over the past four decades. In renal epithelia, the main effect is an increase in
      sodium transport through activation and de novo synthesis of epithelial sodium
      channels. This leads to increased concentrations of intracellular sodium
      activating sodium-potassium-ATPase molecules mainly at the basolateral membrane
      which extrude sodium back into the blood stream. In contrast, rapid steroid
      actions have been widely recognized only recently. The present article summarizes
      both traditional and rapid effects of mineralocorticoid hormones on intracellular
      electrolytes, e.g. free intracellular calcium in vascular smooth muscle cells as
      determined by fura 2 spectrofluorometry in single cultured cells from rat aorta.
      Latter effects are almost immediate, reach a plateau after only 3 to 5 minutes
      and are characterized by high specificity for mineralocorticoids versus
      glucocorticoids. The effect of aldosterone is blocked by neomycin and short-term
      treatment with phorbol esters but augmented by staurosporine, indicating an
      involvement of phospholipase C and protein kinase C. The Ca(2+) effect appears to
      involve the release of intracellular Ca(2+), as shown by the inhibitory effect of
      thapsigargin. This mechanism operates at physiological subnanomolar aldosterone
      concentrations and appears to result in rapid fine tuning of cardiovascular
      responsivity. As a landmark feature of these rapid effects, insensitivity to
      classic antimineralocorticosteroids, e.g. spironolactone or canrenone has been
      found in the majority of observations. In an integrated view, mineralocorticoids
      seem to mainly effect intracellular electrolytes genomically to induce
      transepithelial transport, and induce nongenomically mediated alterations of cell
      function (e.g. vasoconstriction) by rapid effects on intracellular electrolytes
      such as free intracellular calcium.

PMID- 15947891
TI  - The mineralocorticoid receptor and oxidative stress.
AB  - Reactive oxygen species are profoundly important for many physiologic functions
      and are also pivotal to numerous disease processes, particularly those involving
      inflammation. Much evidence has accrued demonstrating that aldosterone acts
      locally in many cells aside from those in the cortical collecting duct.
      Peripheral blood monocytes and vascular smooth muscle cells are both influenced
      by aldosterone to produce reactive oxygen species. This production contributes to
      nuclear factor kappaB (NF-kappaB) activation and the genes regulated by this
      transcription factor. Aldosterone thereby plays an important role in
      atherosclerosis and hypertension-induced vascular injury. Aldosterone interacts
      with angiotensin (Ang) II-induced signaling. Both aldosterone and Ang II initiate
      ERK1/2 and JNK signaling; the effects of the two compounds is additive and
      involves the epidermal growth factor receptor. Recent data suggest that reactive
      oxygen species, might contribute to aldosterone production in nonadrenal tissues.
      A novel oxidized derivative of linoleic acid is a prime candidate in this regard.
      Oxidative stress may impair mineralocorticoid receptor function by inhibiting
      aldosterone binding. The latter finding has particularly important implications
      for elderly persons who exhibit increased oxidative stress and who are at risk
      for diminished aldosterone function in the distal nephron and subsequent
      hyperkalemia.

PMID- 15947892
TI  - Effect of aldosterone and MR blockade on the brain and the kidney.
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a central role in the
      development of hypertension and the progression of end-organ damage. Although
      angiotensin-I converting enzyme (ACE) inhibitors and angiotensin II (Ang II)
      subtype-1 (AT(1)) receptor antagonists can initially suppress plasma aldosterone,
      it is now well established that aldosterone escape may occur whereby aldosterone
      levels return to, or exceed, baseline levels. The classical effects of
      aldosterone relate mainly to its action on epithelial cells to regulate water and
      electrolyte balance. However, the presence of mineralocorticoid receptors (MR) at
      nonepithelial sites in the brain, heart and vasculature, is consonant with the
      fact that aldosterone also has direct effects in these tissues. Substantial
      evidence now exists that supports the action of aldosterone at non-epithelial
      sites which in turn provokes a number of deleterious effects on the
      cardiovascular system including necrosis and fibrosis of the vasculature and the
      heart, vascular stiffening and injury, reduced fibrinolysis, endothelial
      dysfunction, catecholamine release and production of cardiac arrhythmias. Several
      studies have now shown that vascular and target-organ protective effects of MR
      antagonism occurs in the absence of significant blood pressure lowering or fluid
      loss, which is consistent with a major role for endogenous mineralocorticoids as
      direct mediators of cardiovascular injury. Adverse cardiovascular effects may
      occur in response to aldosterone alone, activation of the RAAS or aldosterone
      escape during chronic ACE inhibition or AT(1) receptor antagonism. The specific
      blockade of aldosterone action should prove to be of great therapeutic value in
      the prevention of cerebral and renal vascular disease and associated end-organ
      damage.

PMID- 15947893
TI  - Autonomic effects of spironolactone and MR blockers in heart failure.
AB  - Neurohormonal dysfunction is an important and potentially modifiable part of the
      disease process of heart failure. In this review we will discuss the ways in
      which the autonomic system is deranged in congestive cardiac failure and the
      different ways we have of monitoring these abnormalities i.e.: heart rate
      variability, plasma norephinephrine activity, MIBG scanning, heart rate
      turbulence, baroreceptor function and briefly, microneurographic techniques and
      QT interval analysis. We will then discuss the direct effects of aldosterone and
      of aldosterone blockade on some of these parameters. We conclude that
      neurohormonal dysfunction is an important component of chronic heart failure,
      which is affected by aldosterone and can be modified by the use of aldosterone
      receptor blockade.

PMID- 15947894
TI  - Effect of MR blockade on collagen formation and cardiovascular disease with a
      specific emphasis on heart failure.
AB  - Collagen is the major extracellular matrix protein in the heart and represents a
      crucial target for anti-remodeling and cardioprotective therapy. Collagen
      quantity and quality have been shown to be regulated under various physiological
      and pathologic conditions. Excessive deposition of collagen, leading to cardiac
      fibrosis, is a major determinant of cardiac dysfunction and arrhythmogenecity
      associated with sudden death. Serological markers of collagen turnover were
      proven as a noninvasive reliable tool for monitoring from a distance cardiac
      tissue repair and fibrosis, both in experimental and clinical conditions. Some
      markers of collagen synthesis and degradation were shown to have a prognostic
      significance in myocardial infarction, cardiomyopathy and heart failure, and were
      reported as independent predictors of mortality. Aldosterone represents the end
      product of the renin angiotensin aldosterone system and may play a role in
      cardiac collagen deposition independent of its effect on blood pressure.
      Production of aldosterone is mainly regulated by angiotensin II and is activated
      in the failing human ventricle in proportion to heart failure severity.
      Circulating or locally produced aldosterone stimulates fibrillar collagen
      accumulation in the heart directly via mineralocorticoid receptors or,
      indirectly, modifying angiotensine II receptors number and/or function. The use
      of mineralocorticoid receptor antagonists counters collagen deposition, even when
      used on top of classical RAAS inhibitors, such as ACE inhibitors and angiotensine
      II receptor blockers. There is now accumulating evidence from experimental and
      clinical studies showing antifibrotic and cardioprotective effect for aldosterone
      antagonists, spironolactone and eplerenone. In chronic heart failure and post
      myocardial infarction patients, aldosterone receptor blockade benefit was
      associated with decreased serum levels of collagen synthesis marker PIIINP
      (procollagen type III amino-terminal peptide), without affecting collagen
      degradation. Understanding various autocrine/paracrine mechanisms involved in
      extracellular matrix remodeling in heart failure represents a major challenge,
      essential for developing new cardioreparative and cardioprotective strategies.

PMID- 15947895
TI  - The role of aldosterone blockade in patients with heart failure.
AB  - The mechanisms associated with aldosterone production both systemically and
      locally as well as the effects of aldosterone blockade on the pathophysiology of
      heart failure (HF) have been extensively reviewed in this series and elsewhere.
      This article will review the clinical evidence supporting the use of aldosterone
      blocking agents (AB)in patients with HF and speculate on some potential future
      uses.

PMID- 15947896
TI  - [Are too few doctors being trained in Germany?].

PMID- 15947897
TI  - [Corrective osteotomy of the humerus using perivascular axillary anesthesia
      according to Weber in a patient suffering from McCune-Albright syndrome].
AB  - We report on a 20-year-old patient with McCune-Albright syndrome suffering from
      global respiratory insufficiency who required continuous mask ventilation and
      where intubation had to be avoided. Perivascular axillary anesthesia according to
      Weber was performed for a double corrective osteotomy of the humerus. During
      plexus anesthesia the patient was positioned on the non-anesthesized side in a 15
      degrees Trendelenburg position. An extension of analgesia was observed up to the
      complete upper arm region. Using the modified positioning an extension of
      brachial plexus anesthesia is possible.

PMID- 15947899
TI  - [A rare obstruction of the pharynx].

PMID- 15947898
TI  - [Adrenal cortex and steroids. Supplementary therapy in the perioperative phase].
AB  - Since the publication of two case reports that are considered to represent the
      first clinical demonstration of iatrogenic adrenal insufficiency, it has been the
      generally accepted practice to cover steroid-treated patients undergoing surgery
      with glucocorticoids in the perioperative period. Both the inclusion criteria for
      the patients and the extent of the substitution pattern have been selected on an
      empirical rather than on a rational basis. Scientific advances over the past 50
      years in the knowledge of the hypothalamic-pituitary-adrenal system's physiology
      and the molecular mechanism of action of its biologically active components are,
      for the most part, not reflected in current clinical practice and instead seem to
      be ignored. Clinical and experimental evidence suggests, however, that even
      glucocorticoid-treated patients undergoing surgery do not require maximum stress
      doses of hydrocortisone, which should be reserved for the treatment of sepsis.
      With regard to the broad spectrum of efficacy of glucocorticoids and their side
      effects, revision and modification of the historical regimen appear prudent.

PMID- 15947900
TI  - [The transverse rectus abdominis muscle (TRAM) flap. A "second defensive line" in
      microvascular reconstructions of defects in the head and neck area].
AB  - BACKGROUND: The microvascular anastomosed transverse rectus abdominis muscle
      (TRAM) island flap has been successfully used in plastic surgery for more than 10
      years. In reconstructive head and neck surgery, however, it is not yet
      established. METHOD: We analysed the preparation and anatomical variation in TRAM
      flaps in an examination of eight cadavers. In a clinical case with complete
      reconstruction of the nose after nasal ablation and complete loss of a radial
      lower forearm flap that had been transplanted previously due to a recurrent
      tumor, the possibility of forming and modeling a TRAM flap is demonstrated.
      RESULTS: The flap vessels of the TRAM are comparable to the radial forearm flap,
      and the donor site may be primarily closed. The TRAM proved to be a suitable
      alternative to close lesions of the head and neck area in selected cases. The
      myocutaneous TRAM is bulkier than the fascio-cutaneous radial forearm flap. The
      subcutaneous abdominal fat of the TRAM can be reduced in relation to the vascular
      distribution of the perforator vessels. If the subcutaneous fat of the flap is
      reduced, the flap can be shaped and formed well. In the described case, it was
      used to close the lesion after ablation of the nose and middle face. CONCLUSION:
      The risk of an iatrogenic lesion of the peritoneal fascia or postsurgical
      herniation of the abdominal wall is low if several surgical prerequisites are
      taken into consideration. The myocutaneous TRAM will not replace the fascio
      cutaneous radial forearm flap in microvascular head and neck surgery, but the
      large diameter of the donor vessels and the highly vascularized flap tissue makes
      it an alternative as a second line procedure in cases of unfavorable wound
      conditions.

PMID- 15947901
TI  - [Autoimmune polyglandular syndromes].
AB  - Autoimmune polyglandular syndromes are rare autoimmune endocrinopathies, which
      can be also associated with non endocrine autoimmune diseases. The autoimmune
      polyglandular syndrome type I (autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy; APECED) is distinguished from autoimmune polyglandular
      syndrome type 2 (APS-2). Main symptoms of APECED are adrenal insufficiency,
      hypoparathyroidism and candidiasis. The diagnosis is established when two out of
      three of these symptoms are present. APECED is associated with mutations of the
      autoimmune regulator gene (AIRE) and predominantly affects juvenile patients with
      a family background from Sardinia, Finland and Iranian Jews. The APS-2 is not
      AIRE associated. It is characterized by the presence of autoimmune thyroid
      disease, adrenal insufficiency and/or diabetes mellitus type I. APS-2 is more
      common than APECED and mainly affects adult women without any preference of a
      certain ethnic group. Therapy consists of hormone replacement therapy and
      treatment of clinical symptoms. In some APECED patients immunosuppressive therapy
      seems to be promising.

PMID- 15947902
TI  - [PAFAC Study. Secondary prevention of atrial fibrillation after cardioversion].

PMID- 15947903
TI  - [Erectile dysfunction in men in their second half of life].
AB  - BACKGROUND: Studies to date on the prevalence of erectile dysfunction (ED) report
      varying results. The present study investigates the frequency and degree of ED,
      its determining factors as well as the help-seeking behavior of the patients.
      PATIENTS AND METHODS: A random sample of 628 Swiss men (mean age: 61.5 years)
      were examined by questionnaire regarding their sexual functioning, comorbidity,
      and help-seeking behavior. RESULTS: Of the respondents, 9.6% reported complete,
      18.0% moderate, and 41.4% minimal ED. All grades of the disorder increased with
      age and correlated with somatic and psychiatric comorbidity as well as with drug
      intake. Only 3.2% reported having used drugs for improvement of erectile
      functioning. CONCLUSION: Only a small number of men suffering from ED seek the
      help of a doctor. Considering the efficacy of PDE5 inhibitors, objective
      information and competent medical counseling of ED patients are indicated.

PMID- 15947904
TI  - Microsatellite analysis of Rosa damascena Mill. accessions reveals genetic
      similarity between genotypes used for rose oil production and old Damask rose
      varieties.
AB  - Damask roses are grown in several European and Asiatic countries for rose oil
      production. Twenty-six oil-bearing Rosa damascena Mill. accessions and 13 garden
      Damask roses were assayed by molecular markers. Microsatellite genotyping
      demonstrated that R. damascena Mill. accessions from Bulgaria, Iran, and India
      and old European Damask rose varieties possess identical microsatellite profiles,
      suggesting a common origin. At the same time, the data indicated that modern
      industrial oil rose cultivation is based on a very narrow genepool and that oil
      rose collections contain many genetically identical accessions. The study of long
      term vegetative propagation of the Damask roses also reveals high somatic
      stability for the microsatellite loci analyzed.

PMID- 15947905
TI  - Molecular mapping of Fusarium head blight resistance in the winter wheat
      population Dream/Lynx.
AB  - Fusarium head blight (FHB), mainly caused by Fusarium graminearum and F.
      culmorum, can significantly reduce the grain quality of wheat (Triticum aestivum
      L.) due to mycotoxin contamination. The objective of this study was to identify
      quantitative trait loci (QTLs) for FHB resistance in a winter wheat population
      developed by crossing the resistant German cultivar Dream with the susceptible
      British cultivar Lynx. A total of 145 recombinant inbred lines (RILs) were
      evaluated following spray inoculation with a F. culmorum suspension in field
      trials in 2002 in four environments across Germany. Based on amplified fragment
      length polymorphism and simple sequence repeat marker data, a 1,734 cM linkage
      map was established assuming that the majority of the polymorphic parts of the
      genome were covered. The area under disease progress curve (AUDPC) was calculated
      based on the visually scored FHB symptoms. The population segregated
      quantitatively for FHB severity. Composite interval mapping analysis for means
      across the environments identified four FHB resistance QTLs on chromosomes 6AL,
      1B, 2BL and 7BS. Individually the QTLs explained 19%, 12%, 11% and 21% of the
      phenotypic variance, respectively, and together accounted for 41%. The QTL
      alleles conferring resistance on 6AL, 2BL and 7BS originated from cv. Dream. The
      resistance QTL on chromosome 6AL partly overlapped with a QTL for plant height.
      The FHB resistance QTL on 7BS coincided with a QTL for heading date, but the
      additive effect on heading date was of minor importance. The resistance QTL on
      chromosome 1B was associated with the T1BL.1RS wheat-rye translocation of Lynx.

PMID- 15947906
TI  - Genetic modification of potato against microbial diseases: in vitro and in planta
      activity of a dermaseptin B1 derivative, MsrA2.
AB  - Dermaseptin B1 is a potent cationic antimicrobial peptide found in skin
      secretions of the arboreal frog Phyllomedusa bicolor. A synthetic derivative of
      dermaseptin B1, MsrA2 (N-Met-dermaseptin B1), elicited strong antimicrobial
      activities against various phytopathogenic fungi and bacteria in vitro. To assess
      its potential for plant protection, MsrA2 was expressed at low levels (1-5
      microg/g of fresh tissue) in the transgenic potato (Solanum tuberosum L.) cv.
      Desiree. Stringent challenges of these transgenic potato plants with a variety of
      highly virulent fungal phytopathogens--Alternaria, Cercospora, Fusarium,
      Phytophthora, Pythium, Rhizoctonia and Verticillium species--and with the
      bacterial pathogen Erwinia carotovora demonstrated that the plants had an
      unusually broad-spectrum and powerful resistance to infection. MsrA2 profoundly
      protected both plants and tubers from diseases such as late blight, dry rot and
      pink rot and markedly extended the storage life of tubers. Due to these
      properties in planta, MsrA2 is proposed as an ideal antimicrobial peptide
      candidate to significantly increase resistance to phytopathogens and improve
      quality in a variety of crops worldwide with the potential to obviate fungicides
      and facilitate storage under difficult conditions.

PMID- 15947907
TI  - Molecular mapping of the fertility restorer gene for ms-CW-type cytoplasmic male
      sterility of rice.
AB  - Cytoplasmic male sterility (CMS) of rice (Oryza sativa L.) was first reported
      using the cytoplasm of a Chinese wild rice, Oryza rufipogon Griff. strain W1.
      However, it was not possible to characterize this ms-CW-type CMS in more detail
      until a restorer line had been developed due to the lack of restorer genes among
      cultivars thus far tested. The breeding of a restorer line (W1-R) was eventually
      achieved by transferring the restorer gene(s) of W1 to a cultivar. We report here
      the characterization of the ms-CW pollen grains and mapping of the restorer gene
      for ms-CW-type CMS. Pollen grains of the male-sterile plants appeared to be
      normal and viable based on the fluorochromatic reaction test, but they did not
      germinate on normal stigmas. The 1:1 segregation of fertile and sterile plants in
      a BC(1)F(1) population from a cross between W1-R and a maintainer line
      demonstrated that fertility restoration is controlled by a single gene. The
      fertile seed set of all the F(2) plants examined indicated that the fertility
      restoration functions gametophytically. We designated the fertility restorer gene
      Rfcw. Using cleaved amplified polymorphic sequence (CAPS) and simple sequence
      repeat (SSR) markers, we localized Rfcw to chromosome 4 with a genetic distance
      of 0.6 cM from the nearest SSR marker.

PMID- 15947908
TI  - RYS1, a foldback transposon, is activated by tissue culture and shows
      preferential insertion points into the rye genome.
AB  - The study of two variable amplicons of rye indicates that RYS1, a mobile element,
      is activated during tissue culture. We propose that RYS1 could be a foldback (FB)
      transposon. The FB transposons have been rarely reported in plants; RYS1 is the
      first described in rye and also the first active plant FB transposon reported.
      Preferential integration points in the rye genome exist, because the new
      insertions seem to be located, in all studied cases, in the same genome
      positions. We assume that RYS1 became active in rye very recently, as different
      plants from in vivo-growing cultivars showed that these elements were present or
      absent in the same genomic position in which the in vitro-activated element was
      found. This high rate of modification in these particular loci, both in the in
      vivo and in vitro populations, could indicate that probably the mechanisms
      promoting genetic variability in nature are the same that induce variation in
      vitro, and the modifications induced by somaclonal variation could be already
      present in vivo populations.

PMID- 15947909
TI  - Identification and validation of QTL for Sclerotinia midstalk rot resistance in
      sunflower by selective genotyping.
AB  - Midstalk rot, caused by Sclerotinia sclerotiorum (Lib.) de Bary, is an important
      cause of yield loss in sunflower (Helianthus annuus L.). Objectives of this study
      were to: (1) estimate the number, genomic positions and genetic effects of
      quantitative trait loci (QTL) for resistance to midstalk rot in line TUB-5-3234,
      derived from an interspecific cross; (2) determine congruency of QTL between this
      line and other sources of resistance; and (3) make inferences about the
      efficiency of selective genotyping (SG) in detecting QTL conferring midstalk rot
      resistance in sunflower. Phenotypic data for three resistance (stem lesion, leaf
      lesion and speed of fungal growth) and two morphological (leaf length and leaf
      length with petiole) traits were obtained from 434 F3 families from cross CM625
      (susceptible) x TUB-5-3234 (resistant) under artificial infection in field
      experiments across two environments. The SG was applied by choosing the 60 most
      resistant and the 60 most susceptible F3 families for stem lesion. For genotyping
      of the respective F2 plants, 78 simple sequence repeat markers were used.
      Genotypic variances were highly significant for all traits. Heritabilities and
      genotypic correlations between reMidstalk rot, caused by Sclerotinia sclerotiorum
      (Lib.) de Bary, is an important cause of yield loss in sunflower (Helianthus
      annuus L.). Objectives of this study were to: (1) estimate the number, genomic
      positions and genetic effects of quantitative trait loci (QTL) for resistance to
      midstalk rot in line TUB-5-3234, derived from an interspecific cross; (2)
      determine congruency of QTL between this line and other sources of resistance;
      and (3) make inferences about the efficiency of selective genotyping (SG) in
      detecting QTL conferring midstalk rot resistance in sunflower. Phenotypic data
      for three resistance (stem lesion, leaf lesion and speed of fungal growth) and
      two morphological (leaf length and leaf length with petiole) traits were obtained
      from 434 F3 families from cross CM625 (susceptible) x TUB-5-3234 (resistant)
      under artificial infection in field experiments across two environments. The SG
      was applied by choosing the 60 most resistant and the 60 most susceptible F3
      families for stem lesion. For genotyping of the respective F2 plants, 78 simple
      sequence repeat markers were used. Genotypic variances were highly significant
      for all traits. Heritabilities and genotypic correlations between resistance
      traits were moderate to high. Three to four putative QTL were detected for each
      resistance trait explaining between 40.8% and 72.7% of the genotypic variance
      (PTS). Two QTL for stem lesion showed large genetic effects and corroborated
      earlier findings from the cross NDBLOSsel (resistant) x CM625 (susceptible). Our
      results suggest that SG can be efficiently used for QTL detection and the
      analysis of congruency for resistance genes across populations.

PMID- 15947910
TI  - Insulin resistance and the metabolic syndrome.

PMID- 15947911
TI  - To: Strey CH, Young J, Collier M, Florkowski CM, Shand BI, Scott RS (2004) The
      postprandial state does not impair endothelial function in women with Type 2
      diabetes irrespective of glycaemic control. Diabetologia 47:1838-1846.

PMID- 15947912
TI  - Femoral avulsion fracture of the posterior cruciate ligament in association with
      a rupture of the popliteal artery in a 9-year-old boy: a case report.
AB  - Ruptures of the posterior cruciate ligament (PCL) and especially proximal bony
      avulsion fractures in children are very rare. This in combination with a rupture
      of the popliteal artery is extremely rare. Thus, an exact incidence is not
      available from the literature. Overall, these injuries are severe and often lead
      to chronic knee instability. We report a case of a 9-year-old boy who suffered a
      traumatic displacement of the left knee with a rupture of the popliteal artery.
      Prior to transfer to our department, he was treated by a saphenous vein bypass
      graft and by a transfixation of the knee using two oblique percutaneous pins. We
      performed magnetic resonance imaging (MRI) scan of the knee which revealed a
      femoral avulsion fracture of the PCL. Other ligaments and menisci were intact. A
      transosseous femoral fixation using non-absorbable stitches was carried out. A 1
      year follow-up after surgery demonstrates intact peripheral perfusion and
      sensation, straight axes of both legs and a physiological gait. Minimal
      differences of the length and circumference of both legs could be measured. The
      posterior laxity (Lachman-test) was about 5/8 mm (right/left knee) and 2/5 mm
      (right/left knee) in 90 degrees flexion. The range of motion (extension/flexion)
      was 5/0/140 degrees -/5/100 degrees (right-left knee). Intact cruciate ligaments
      were confirmed by MRI. Minimal experience exists in treatment of combined
      injuries to the PCL and the popliteal artery in children.

PMID- 15947913
TI  - The postoperative analgesic effects of intra-articular levobupivacaine in
      elective day-case arthroscopy of the knee: a prospective, randomized, double
      blind clinical study.
AB  - PURPOSE: Pain and emesis are the two major complaints after day surgery. Local
      anesthesia has become an important part of optimizing perioperative pain
      treatment. The aim of the present study was to study two different concentrations
      of levobupivacaine's effect on postoperative pain following elective arthroscopy
      of the knee with lidocaine 10 mg/ml with adrenaline as active control. TYPE OF
      STUDY: Prospective, randomized double-blind study with lidocaine as active
      control but without placebo. METHODS: One hundred and twenty patients were
      studied comparing levobupivacaine 2.5 mg/ml, levobupivacaine 5 mg/ml, and
      lidocaine 10 mg/ml with adrenaline given intra-articularly at the end of day-case
      operative elective arthroscopy of the knee done in light general anesthesia.
      Primary study endpoint was the need for any analgesics during the first 24
      postoperative hours. RESULTS: Levobupivacaine 5 mg/ml was associated with a
      reduced need for any analgesia during the entire 24-h study period (p = 0.013) as
      compared to both 2.5 mg/ml levobupivacaine and lidocaine with adrenaline.
      Levobupivacine 2.5 mg/ml was inferior to lidocaine with regard to pain relief
      with an increase in need for oral analgesia already during stay in the recovery
      unit (p < 0.001). CONCLUSIONS: Levobupivacaine 5 mg/ml was found to be an
      effective local anesthetic in day-case operative arthroscopy of the knee
      providing superior postoperative analgesia as compared to lidocaine with
      adrenaline or a lower concentration of levobupivacaine. LEVEL OF EVIDENCE: Level
      I: Prospective, randomized double-blind study without placebo.

PMID- 15947914
TI  - Thermal modification of the lax anterior cruciate ligament using radiofrequency:
      efficacy or catastrophe?
AB  - Alchemists dream of using energy to turn base metal to gold. "Shrinkers" use
      energy to transform laxity to stability. While alchemists search for the
      mechanism to achieve their goal, shrinkers have thermal energy (heat) and
      scientific ground for their pursuit. Without doubt, application of heat to
      collagen using radiofrequency (RF) results in tissue shrinkage. However, with
      regard to thermal shrinkage of a lax anterior cruciate ligament (ACL) or ACL
      graft, indications and techniques, rehabilitation and outcomes require review.
      Such is the purpose of this article.

PMID- 15947915
TI  - A dynamic continuous-flow dialysis system with on-line electrothermal atomic
      absorption spectrometric and pH measurements for in-vitro determination of iron
      bioavailability by simulated gastrointestinal digestion.
AB  - A dynamic continuous-flow dialysis (CFD) method with on-line electrothermal
      atomic absorption spectrometric (ETAAS) and pH measurements for study of
      simulated gastrointestinal digestion has been developed for prediction of iron
      bioavailability. The method used to estimate mineral bioavailability was based on
      gastric digestion in a batch system then dynamic continuous-flow intestinal
      digestion. The intestinal digestion was performed in a dialysis bag placed inside
      a chamber containing a flowing stream of dialyzing solution. Mineral
      concentration and dialysate pH were monitored by ETAAS and use of a pH meter,
      respectively. The amount of dialyzed minerals in the intestinal digestion stage
      was used to evaluate the dialyzability. The dialysis profile and pH change can be
      used to understand or examine differences between the dialyzability of different
      food samples. To test the proposed system it was used to estimate the iron
      dialyzability of different kinds of milk. Iron dialyzability for powdered cow
      milk, cereal milk, and two brands of soymilk was found to be 1.7, 20.4, 24.9, and
      37.7%, respectively. The developed CFD-ETAAS-pH system is a simple, rapid, and
      inexpensive tool for bioavailability studies, especially for minerals at
      ultratrace levels.

PMID- 15947916
TI  - Time-resolved monitoring of heavy-metal intoxication in single hair by laser
      ablation ICP-DRCMS.
AB  - The potential of laser ablation inductively coupled plasma mass spectrometry for
      the time-resolved analysis of heavy-metal intoxication in human bodies by
      analysis of hair is demonstrated. As application, we analyzed forensic samples
      from one individual after Hg intake and from one treated with a Pt-containing
      cytostatic remedy. Single hairs were analyzed from the hair root to the tip by
      laser ablation ICP-MS with a spatial resolution of 20 mum (corresponding to
      approx. 2 h growth of the hair). Sulfur was used as internal standard and was
      analyzed by using oxygen as reaction gas in the dynamic reaction cell of the ICP
      DRCMS. The detection limits for Hg and Pt were found to be 0.3 microg g(-1) and
      0.5 ng g(-1), respectively. Standard uncertainties for the quantification results
      were 10% for Hg and approximately 15 % for Pt. The analyzed hair samples
      reflected the forensic evidence in both cases. A significant increase of Hg
      concentration, by a factor of 50, at the time of HgO administration could be
      shown, and variation of Pt in the hair strands could be used to monitor the time
      and relative amount of Pt intake by the patient. The investigations also revealed
      that the concentrations in the outer and the inner parts of the hair varied
      similarly with time, even though the concentration in the core of the hair is
      approximately 0.25 that at the surface for both Pt and Hg.

PMID- 15947917
TI  - Investigation of 2-[(E)-2-(4-diethylaminophenyl)-1-ethenyl]-1,3,3-trimethyl-3H
      indolium as a new highly sensitive reagent for the spectrophotometric
      determination of nitrophenols.
AB  - A new, simple, rapid, and sensitive spectrophotometric method has been developed
      for the determination of nitrophenols [picric acid (PA); dinitrophenols (DNP)] in
      wastewater samples. The method is based on the reaction of nitrophenols with 2
      [(E)-2-(4-diethylaminophenyl)-1-ethenyl]-1,3,3-trimethyl-3 H-indolium chloride
      reagent to form the colored ion associates, which are extracted by organic
      solvents. The molar absorptivity of the ion associates of PA with the
      investigated reagent ranges from 8.3x10(4) to 11.3 x 10(4) L mol(-1) cm(-1),
      depending on the extractant. Because only PA is extracted in an acidic medium
      with the investigated reagent, but both PA and DNP are extracted in an alkaline
      medium, it is possible to determine both substances in a mixture. Appropriate
      reaction conditions have been established. The absorbance of the colored extracts
      obeys Beer's law in the range of 0.04-4.58 mg L(-1) PA, 1.0-18.4 mg L(-1) 2,4-DNP
      and 1.2-14.7 mg L(-1) 2,6-DNP, respectively. The limit of detections, calculated
      from a blank test (n=10; P=0.95), are 0.05 mg L(-1) PA, 0.9 mg L(-1) (2,4-DNP),
      and 1.1 mg L(-1) (2,6-DNP), respectively.

PMID- 15947918
TI  - Semicarbazide: occurrence in food products and state-of-the-art in analytical
      methods used for its determination.
AB  - This review provides an overview of the information currently available about the
      presence of semicarbazide (SEM) in food. Likely sources of SEM in food matrices
      are summarised and discussed. Detailed information is given about the analytical
      methods used to determine SEM; features and drawbacks associated with them are
      carefully evaluated. Performance criteria characterising the analytical methods
      discussed are also given.

PMID- 15947919
TI  - Learning and recall of incremental kinematic and dynamic sensorimotor
      transformations.
AB  - Numerous studies have shown that when people encounter a sudden and novel
      sensorimotor transformation that alters perceived or actual movement, they
      gradually adapt and can later recall what they have learned if they encounter the
      transformation again. In this study, we tested whether retention and recall of
      learning is also observed when kinematic and dynamic transformations are
      introduced incrementally such that participants never experience large movement
      errors. Participants adapted their reaching movements to either a visuomotor
      rotation of hand position (kinematic transformation) or a rotary viscous force
      field applied to the hand (dynamic transformation). These perturbations were
      introduced either incrementally or instantaneously. Thus, four groups of
      participants were tested with an incremental and an instantaneous group for both
      the kinematic and dynamic perturbations. To evaluate retention of learning,
      participants from all four groups were tested a day later on the same kinematic
      or dynamic perturbation presented instantaneously (at full strength). As
      expected, we found that subjects in the instantaneous group retained learning
      across days. We also found that, for both kinematic and dynamic perturbations,
      retention was equally good or better when the transformation was introduced
      incrementally. Because large and clearly detectable movement errors were not
      observed during adaptation to incremental perturbations, we conclude that such
      errors are not required for the learning and retention of internal models of
      kinematic and dynamic sensorimotor transformations.

PMID- 15947920
TI  - Main comedications associated with major bleeding during anticoagulant therapy
      with coumarins.
AB  - OBJECTIVE: To study the main comedications associated with major bleeding during
      anticoagulant therapy with coumarins in a non-selected population under everyday
      circumstances. METHODS: The study population for this retrospective cohort study
      included all new users of phenprocoumon or acenocoumarol aged 40-80 years, during
      the period 1992-2000 in the PHARMO Record Linkage System. All patients were
      followed until the last dispensing of phenprocoumon or acenocoumarol, the first
      bleeding complication requiring hospitalization, death, or the end of the study
      period. The number of days on coumarins alone and the number of days on coumarins
      in combination with several potentially interactive drugs during follow-up were
      determined for each patient. RESULTS: The inclusion criteria of this study were
      met by 19,935 new users of phenprocoumon or acenocoumarol. During follow-up, 552
      patients were hospitalized for bleeding. Of all potentially interactive drugs
      started during anticoagulant therapy by at least 50 patients and with at least
      five bleedings, antibacterial drugs were associated with a four to seven times
      increased risk of bleeding. Among non-steroidal anti-inflammatory drugs, naproxen
      had the highest relative risk. Antithrombotic salicylates and tramadol were
      associated with a three times increased risk of bleeding. CONCLUSION:
      Antibacterial drugs, non-steroidal anti-inflammatory drugs, antithrombotic
      salicylates and tramadol were the main potentially interactive drugs associated
      with major bleeding during anticoagulant therapy with coumarins under everyday
      circumstances.

PMID- 15947921
TI  - Transfer of rofecoxib into human milk.
AB  - OBJECTIVE: To determine the milk-to-plasma (M/P) concentration ratio of rofecoxib
      in lactating mothers and estimate likely infant exposure. METHODS: Rofecoxib 25
      mg was given to six lactating women at weaning. Blood and milk were sampled up to
      72 h post-dose for determination of rofecoxib concentrations. M/P ratios were
      derived from the respective area under the concentration-time curves. The infant
      'dose' in milk was estimated and expressed as a percentage of the maternal dose,
      corrected for weight. RESULTS: The median (range) M/P ratio and infant 'dose'
      were 0.25 (0.16-0.32) and 2.1% (1.8-3.2%), respectively. CONCLUSIONS: The use of
      rofecoxib during breastfeeding is unlikely to pose harm to the suckling infant on
      the basis of low transfer into human milk.

PMID- 15947922
TI  - Continuity of long-term medication use after surgical hospital stay.
AB  - OBJECTIVES: To investigate changes in long-term medication during the transfer
      between surgical hospital and primary care. To examine differences in defined
      daily doses (DDDs) versus real prescribed daily doses (PDDs). METHODS: During a
      15-month period, patients from three surgical wards in a university-based
      teaching hospital were asked about their medication at admission (T1), at
      discharge (T2), and 3 months after discharge (T3). Complete data were obtained
      for 299 patients (169 women, 130 men; mean age 69.5 years). Both DDD and PDD were
      calculated for each drug. Analysis of data was performed using a relational
      database. RESULTS: Patients took 3.6 drugs (+/-2.2) at T1, 5 (+/-2.4) at T2, and
      3.8 (+/-3.1) at T3. After surgical intervention, a discontinuation of analgesic,
      anti-rheumatic, and thyroid medication was observed frequently (35% of
      discontinued drugs at T2). We found more drug alterations at T3 than at T2 (263
      versus 87). Family doctors mostly changed medications prescribed for the
      cardiovascular system (22% of all cardiovascular agents were discontinued and/or
      started at T3). We could not determine those changes to be methodical. The total
      of PDDs and DDDs did not differ, but the mean PDDs of statins and beta-blocking
      agents were significantly below the DDDs (P<0.005). CONCLUSION: The observed
      changes in medication after hospitalization can be only partially attributed to a
      successful surgical intervention and to the hospital stay. Those alterations
      seemed not to be initiated by the intention of saving costs.

PMID- 15947925
TI  - A brainstem variant of reversible posterior leukoencephalopathy syndrome.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is caused by various
      heterogeneous factors, the commonest being hypertension, followed by
      nonhypertensive causes such as eclampsia, renal diseases and immunosuppressive
      therapy. Patients with RPLS exhibit bilateral white and gray matter abnormalities
      in the posterior aspects of the cerebral hemispheres. However, this syndrome may
      affect the brainstem predominantly, and these cases are designated as
      hypertensive brainstem encephalopathy. We present here two patients with
      reversible brainstem encephalopathy: one with hypertension and the other without
      hypertension. These patients presented with swelling and diffuse hyperintensities
      of the brainstem in fluid-attenuated inversion-recovery (FLAIR) and T2-weighted
      MRI, but with relatively mild clinical symptoms. They recovered without major
      neurological deficits, but had residual lacunar lesions in the pons. Reversible
      brainstem encephalopathy with characteristic MRI features was found in both
      hypertensive and nonhypertensive patients. These patients were diagnosed with a
      brainstem variant of RPLS, which is potentially fully reversible after an
      adequate treatment, and therefore should be carefully differentiated from other
      brainstem disease conditions.

PMID- 15947923
TI  - Dermal absorption of permethrin following topical administration.
AB  - OBJECTIVE: Permethrin is an insecticide used in the treatment of lice and scabies
      infections. Although its efficacy and safety have been well documented,
      pharmacokinetic data are sparse. The objective of this study was to determine the
      systemic exposure of permethrin and the duration of residence in the human body
      following topical administration. METHODS: The study consisted of three parts. In
      six young healthy men (part 1), 50 ml of an ethanolic solution containing 215 mg
      permethrin (cis/trans: 25/75) was administered to the hair of the head. In
      another six young healthy men (part 2) and in six male or female scabies patients
      (part 3), 60 g of cream containing 3 g permethrin was administered to the skin of
      the whole body. Urine was collected up to 168 h post-dose. Urinary excretion of
      the main metabolite of permethrin, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane
      carboxylic acid, and its conjugates was measured using a gas
      chromatography/electron capture detection method. RESULTS: Pharmacokinetics were
      similar in all study parts. The time of maximal urinary excretion rate was 12.3,
      20.0 and 14.6 h, terminal elimination half-life was 32.7, 28.8 and 37.8 h and
      urinary recovery of the metabolite reached 0.35, 0.47 and 0.52 M percent of the
      permethrin dose, respectively, in parts 1, 2 and 3 (means). The treatment was
      well tolerated. CONCLUSIONS: The extent of systemic exposure following external
      therapeutic administration of permethrin is very low compared with doses used for
      preclinical toxicity studies, and elimination is virtually complete after 1 week.
      These data provide the pharmacokinetic basis for the clinical safety of topical
      permethrin.

PMID- 15947927
TI  - Hb SE disease: a clinico-hematological profile.
AB  - Hb S and Hb E are globally common hemoglobinopathies. However, Hb SE double
      heterozygous state is uncommon, with only 25 cases reported so far in literature.
      We present two more cases. One presented with gallstones, and the other was
      asymptomatic. This type of disorder was previously described as a relatively
      asymptomatic condition compared to HbSS. A review of the 25 reported cases in
      literature shows that 40.7% (11/27) of these cases are symptomatic. Gender,
      hematological parameters and levels of Hb S, E or F do not predict clinical
      severity.

PMID- 15947926
TI  - Surveillance of intracranial aneurysms treated with detachable coils: a
      comparison of MRA techniques.
AB  - Two MRA techniques were evaluated for the follow-up of coiled intracranial
      aneurysms. Twenty-nine coiled aneurysms were evaluated for a total of 36 follow
      up assessments using 3D time-of flight MRA (TOF MRA), an auto-triggered elliptic
      centric-ordered three-dimensional gadolinium-enhanced MR angiogram (ATECO MRA),
      as well as a selective digital subtraction angiography (DSA), which served as the
      "gold standard". Confident visualization was seen in 36 (100%) of ATECO MRAs and
      in 32 (89%) of the TOF MRAs. Eleven residual aneurysm components (RACs) greater
      than 2 mm were described on DSA. Of these, nine were seen on ATECO MRA
      (sensitivity of 81% and specificity of 88%) and four were seen on TOF MRA
      (sensitivity of 40% and specificity of 90%). The two RACs not seen on ATECO MRA
      both measured 3 mm. The six RACs not seen on TOF MRA measured 3, 4 and 5 mm.
      ATECO MRA provides a non-invasive reliable angiogram for the surveillance of
      coiled aneurysms and is superior to TOF MRA for this purpose.

PMID- 15947928
TI  - Combination chemotherapy with gemcitabine and biotherapy with opioid growth
      factor (OGF) enhances the growth inhibition of pancreatic adenocarcinoma.
AB  - Gemcitabine is the standard of care for advanced pancreatic neoplasia, and exerts
      its effect through inhibition of DNA synthesis. However, gemcitabine has limited
      survival benefits. Opioid growth factor (OGF) is an autocrine-produced peptide
      that interacts with the nuclear receptor, OGFr, to inhibit cell proliferation but
      is not cytotoxic or apoptotic. The present study was designed to examine whether
      a combination of chemotherapy with gemcitabine and biotherapy with OGF is more
      effective than either agent alone in inhibiting pancreatic cancer growth in vitro
      and in vivo. The combination of OGF (10(-6) M) and gemcitabine (10(-8) M) reduced
      MIA PaCa-2 cell number from control levels by 46% within 48 h, and resulted in a
      growth inhibition greater than that of the individual compounds. OGF in
      combination with 5-fluorouracil also depressed cell growth more than either agent
      alone. The action of OGF, but not gemcitabine, was mediated by a naloxone
      sensitive receptor, and was completely reversible. OGF, but no other endogenous
      or exogenous opioids, altered pancreatic cancer growth in tissue culture. The
      combination of OGF and gemcitabine also repressed the growth of another
      pancreatic cancer cell line, PANC-1. MIA PaCa-2 cells transplanted into athymic
      mice received 10 mg/kg OGF daily, 120 mg/kg gemcitabine every 3 days; 10 mg/kg
      OGF daily and 120 mg/kg gemcitabine every 3rd day, or 0.1 ml of sterile saline
      daily. Tumor incidence, and latency times to tumor appearance, of mice receiving
      combined therapy with OGF and gemcitabine, were significantly decreased from
      those of the control, OGF, and gemcitabine groups. Tumor volumes in the OGF,
      gemcitabine, and OGF/gemcitabine groups were markedly decreased from controls
      beginning on days 14, 12, and 8, respectively, after tumor cell inoculation.
      Tumor weight and tumor volume were reduced from control levels by 36-85% in the
      OGF and/or gemcitabine groups on day 45 (date of termination), and the group of
      mice exposed to a combination of OGF and gemcitabine had decreases in tumor size
      of 70% and 63% from the OGF or the gemcitabine alone groups, respectively. This
      preclinical evidence shows that combined chemotherapy (e.g. gemcitabine) and
      biotherapy (OGF) provides an enhanced therapeutic benefit for pancreatic cancer.

PMID- 15947929
TI  - Correlation of pharmacokinetics with the antitumor activity of Cetuximab in nude
      mice bearing the GEO human colon carcinoma xenograft.
AB  - PURPOSE: The epidermal growth factor receptor (EGFR), a protein tyrosine kinase
      expressed in many types of human cancers including colon and breast, has been
      strongly associated with tumor progression. Cetuximab, an IgG1 anti-EGFR chimeric
      mouse/human monoclonal antibody, has been proven to be effective in the treatment
      of advanced colon cancer. To date, there has not been a study to systematically
      evaluate the pharmacokinetics (PK) of Cetuximab in a preclinical model and to
      further explore any correlation of drug exposure between animal models and cancer
      patients. In the present study, we characterized the PK of Cetuximab in nude mice
      at efficacious dose levels and further compared the preclinical optimal dose and
      active plasma drug concentration with those determined in clinical studies.
      EXPERIMENTAL DESIGN: The antitumor activity of Cetuximab was evaluated using the
      GEO human colon carcinoma xenografts implanted subcutaneously in nude mice. The
      drug was administered ip every 3 days for five total injections (inj) (q3dx5) at
      dose levels ranging from 1 mg/inj to 0.04 mg/inj. The plasma PK of Cetuximab was
      determined at dose levels of 1.0, 0.25, and 0.04 mg/inj with a single bolus iv or
      ip administration in nude mice. The tumoral PK of Cetuximab was determined at
      dose levels of 0.25, and 0.04 mg/inj with a single bolus ip administration in
      nude mice bearing GEO tumor xenografts. The plasma and tumoral levels of
      Cetuximab were quantitated by an ELISA assay. RESULTS: Cetuximab demonstrated a
      dose-dependent antitumor activity at dose levels of 0.25, 0.1, and 0.04 mg/inj,
      with a statistically significant tumor growth delay (in reaching a tumor target
      size of 1 gm) of 18 days (P < 0.001), 12.3 days (P < 0.01), and 10 days (P <
      0.01) for 0.25, 0.1, and 0.04 mg/inj, respectively. A separate study employing
      the same treatment schedule showed that Cetuximab was equally active at dose
      levels ranging from 0.25 mg/inj to 1 mg/inj. Therefore, dose levels of Cetuximab
      from 1 mg/inj to 0.04 mg/inj can be considered to be within the efficacious
      range, while dose levels of 0.25 mg/inj or higher appeared to be optimal for the
      antitumor activity of Cetuximab in the GEO tumor model. When Cetuximab was given
      iv to mice, the elimination half life (t(1/2)) was 39.6, 37.8, and 42.2 h for
      doses of 1.0, 0.25, and 0.04 mg/inj, respectively, suggesting a similar
      disposition kinetics of Cetuximab within this dose range. The volume of
      distribution (V(d)) ranged from 0.062 l/kg to 0.070 l/kg, suggesting that
      Cetuximab is primarily confined to the plasma compartment with limited peripheral
      tissue distribution. Clearance (CL) was similar and no apparent PK saturation was
      observed across the dose ranging from 0.04 mg/inj to 1.0 mg/inj. When mice were
      administered with a single bolus ip administration at doses of 1, 0.25, and 0.04
      mg/inj, the maximum plasma concentration (C(max)) was 407.6, 66.4, and 16.5
      microg/ml. The area under the curve of plasma drug concentration (AUC) was
      19212.4, 3182.4, and 534.5 microg/ml h, for 1.0, 0.25, and 0.04 mg/inj,
      respectively. The average steady state plasma concentration (C(ss avg)) for the
      multiple dosing schedule was estimated to be 73.1 microg/ml at 0.25 mg/inj and
      was considered as an active plasma drug concentration. The maximum tumoral
      concentration of Cetuximab was 2.6 and 0.53 ng/mg-tumor while the tumoral drug
      exposure was 112.6 and 18.3 ng/mg h for 0.25 and 0.04 mg/inj, respectively. The
      EGFR was estimated to be nearly completely occupied by Cetuximab at the optimal
      dose of 0.25 mg/inj. CONCLUSION: In the present study, we compared the
      preclinical optimal dose and the corresponding active plasma concentration
      determined in mice with those being observed in cancer patients, i.e. 65-100
      microg/ml. The preclinical optimal dose of 0.25 mg/inj was significantly lower
      than the current clinical dose. However, the active plasma concentration at 0.25
      mg/inj is within the range of the active drug concentrations in cancer patients
      treated with Cetuximab under the current optimal dosing regimen. It appears that
      the active plasma drug concentration determined in preclinical model predicts
      better than the optimal preclinical dose for the clinical development of antibody
      drugs.

PMID- 15947930
TI  - The angiogenesis inhibitor NM-3 is active against human NSCLC xenografts alone
      and in combination with docetaxel.
AB  - The novel isocoumarin 2-(8-hydroxy-6-methoxy-1-oxo-1 H-2-benzopyran-3-yl)
      propionic acid (NM-3) has completed phase I clinical evaluation as an orally
      bioavailable angiogenesis inhibitor. NM-3 directly kills both endothelial and
      tumor cells in vitro at low mM concentrations and is effective in the treatment
      of diverse human tumor xenografts in mice. The present work has assessed the
      activity of NM-3 against human non-small-cell lung cancer (NSCLC) cells when used
      alone and in combination with docetaxel. The results demonstrate that NM-3
      decreases clonogenic survival of NSCLC cells at clinically achievable
      concentrations. The results also demonstrate that NM-3 is effective in the
      treatment of NSCLC (A549, NCI-H460) tumor xenografts in mice. Moreover, NM-3
      potentiated the antitumor activity of docetaxel against NSCLC xenografts without
      increasing toxicity. Our findings indicate that NM-3 may be effective alone or in
      combination with docetaxel in the treatment of patients with NSCLC.

PMID- 15947931
TI  - Magnesium depletion enhances cisplatin-induced nephrotoxicity.
AB  - PURPOSE: Nephrotoxicity and magnesium (Mg)-depletion are well-known side effects
      to cisplatin (CP) treatment. The purpose of this present study was to investigate
      the role of Mg on CP induced changes in renal function. CP induced renal
      dysfunction was achieved by treatment with CP or vehicle (2.5 mg/kg) once weekly
      for 3 weeks. Since the CP-induced renal damage, including tubular reabsorption
      defects, is most prominent within the outer medulla (OM), changes in the
      expression pattern of OM aquaporins and sodium transporters including the Na,K
      ATPase (alpha-subunit), type III Na,H-exchanger (NHE3), aquaporin 1 (AQP1) and 2
      (AQP2) and the Na,K,2Cl-cotransporter (NKCC2) were investigated by semi
      quantitative Western blotting. EXPERIMENTAL DESIGN: Rats had access to either a
      diet with standard Mg or to a Mg-depleted diet. Cisplatin was administered to
      female Wistar rats once a week for 3 weeks according to four regimens: (1)
      Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with standard Mg, (2)
      Cisplatin 2.5 mg/kg body weight i.p., to rats on a diet with low Mg, (3) Isotonic
      NaCl 2.5 ml/kg body weight i.p., to rats on a diet with standard Mg, (4) Isotonic
      NaCl 2.5 ml/kg body weight i.p., to rats on a diet with low Mg. RESULTS: CP had
      no effect on plasma creatinine or urea in rats with standard Mg intake, but the
      expression of all five transporters was significantly reduced when compared to
      vehicle treated rats on standard Mg-intake. Vehicle treated rats on low Mg-intake
      had a significant reduction in the expression of Na,K-ATPase, NHE3 and NKCC2, but
      unchanged expression levels of AQP1 or AQP2 when compared to standard treated
      controls. Forty percent of the CP-treated rats on low Mg-intake died during the
      experiment and the remaining animals had marked increased plasma creatinine and
      urea. Furthermore, the Western blot analysis revealed an almost complete
      disappearance of all four transporters, suggesting a dramatic synergistic effect
      of CP and Mg-depletion on renal function including the expression pattern of
      outer medullary sodium transporters and aquaporins. CONCLUSIONS: This study
      indicates a substantial additive effect of Mg-depletion on cisplatin induced
      renal toxicity as evidenced by significant changes in plasma creatinine and urea,
      renal failure induced mortality and loss of renal transporters. This should give
      cause for concern since the nephrotoxicity observed during cisplatin treatment
      might be substantiated by the known Mg-loss associated with cisplatin treatment
      especially in patients suffering from intense gastro-intestinal side effects.

PMID- 15947932
TI  - Spectrophotometric investigation of the chemical compatibility of the anticancer
      drugs irinotecan-HCl and epirubicin-HCl in the same infusion solution.
AB  - The use of infusional chemotherapy, especially in an ambulatory setting,
      absolutely requires that the individual agents remain stable in solution at room
      temperature and that the drugs be compatible. Because of this, investigation of
      the chemical compatibilities of chemotherapeutic drug combinations given in the
      same infusion solution is quite important especially if the drugs are to remain
      in solution for long periods. Thus, the visual and chemical compatibility of
      irinotecan and epirubicin in the same infusion solution were investigated using
      both reference standards and pharmaceutical dosage forms. No sign of
      incompatibility was observed upon visual examination by means of effervescence,
      pH change, precipitation and colour change. But a chemical incompatibility was
      observed using a spectrophotometric method in the spectra of irinotecan-HCl and
      epirubicin-HCl. The molar ratio of epirubicin-HCl/irinotecan-HCl at which the
      interaction reached a maximum was found to be 2:1. The chemical interaction
      occurred immediately after admixing and no visual or spectral change was noticed
      for 24 h after the interaction had occurred. It is concluded that these drugs are
      chemically incompatible. While the applicability of these two drugs in
      combination is investigated in further pharmacological studies, their chemical
      interaction should also be a consideration. The positive or negative contribution
      of this interaction to the pharmacological effect of the combination might be of
      importance, and therefore should be investigated in further clinical trials.

PMID- 15947933
TI  - S-phase modulation by irinotecan: pilot studies in advanced solid tumors.
AB  - Two studies of irinotecan (CPT-11) followed 24 h later by an antimetabolite were
      conducted. The objectives of the studies were: (1) to determine whether the
      increase in S-phase in tumor cells seen 24 h after CPT-11 administration in
      animal studies is seen in advanced solid tumors in patients, (2) to determine the
      dose of CPT-11 required to produce this effect, (3) to compare two methods
      (immunohistochemistry, IHC, for cyclin A, and DNA flow cytometry, FC) for
      evaluating S-phase in tumor biopsies from patients, and (4) to establish the
      maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of CPT-11, given 24
      h before gemcitabine (GEM, 1000 mg/m(2)). In one study CPT-11 was followed 24 h
      later by 5-fluorouracil (5-FU), 400 mg/m(2) per week for 4 weeks every 6 weeks.
      Tumor biopsies were obtained before and 24 h after CPT-11 administration before
      administration of 5-FU and assayed for S-phase by IHC for cyclin A and by FC. The
      starting dose of CPT-11 was 80 mg/m(2) per week with subsequent exploration of 40
      and 60 mg/m(2) per week to establish the dose-effect relationship of the increase
      in tumor cells in S-phase. In the second study, CPT-11 was given 24 h before GEM
      1000 mg/m(2) per week for 2 weeks every 3 weeks. Doses of 20-80 mg/m(2) were
      explored to establish the MTD and DLT and to study tumor cell S-phase in selected
      patients. CPT-11 80 mg/m(2) produced a mean increase in S-phase by IHC for cyclin
      A of 137%. Lesser increases were seen with 40 and 60 mg/m(2). CPT-11 followed 24
      h later by 5-FU 400 mg/m(2) per week for 4 weeks was well tolerated. In the study
      of CPT-11 followed by GEM 1000 mg/m(2), 60 mg/m(2) of CPT-11 was the MTD.

PMID- 15947934
TI  - Carcinoma colon associated with tuberculosis: an unusual presentation.

PMID- 15947935
TI  - Complications and recurrence after excision of rectal internal mucosal prolapse
      for obstructed defaecation.
AB  - BACKGROUND: Rectal internal mucosal prolapse (RIMP) may cause obstructed
      defaecation and encouraging short-term results have been reported after its
      transanal excision. The objective of this retrospective study was to assess both
      clinical and functional outcome after this procedure alone for patients
      presenting with evacuatory difficulty. PATIENTS AND METHODS: Forty patients (30
      females, mean age 54 years), all suffering from obstructed defaecation, underwent
      RIMP excision at our unit during the last 11 years. RIMP was of first degree in
      three patients, of second degree in 21, and of third degree in 16 with 28/40
      cases (70%) having associated anorectal pathology. The operation was carried out
      by hand suture (submucosal excision, Sarles endorectal excision, or the Delorme
      mucosectomy) in 26 patients, by circular stapled prolapsectomy in nine patients,
      or by combined manual and stapled techniques in five cases. Proctoscopy was
      carried out after 2 months for all patients, with anorectal manometry in 30
      patients. Patients were independently assessed by state-trait anxiety scales for
      attendant anxiety and depression. RESULTS: Eighteen patients (45%) had
      significant postoperative complications with a surgical reintervention rate of
      32.5%. Overall, 21 patients (52%) reported recurrent constipation and of these 14
      (65%) had recurrent RIMP; six patients were treated successfully by rubber-band
      ligation alone. Two patients (5%) experienced new onset faecal incontinence. The
      recurrence rate of RIMP was unaffected by the type of operation, being 53% after
      manual techniques and 48% after combined procedures. There was no difference
      between postoperative manometric values in patients presenting with recurrent
      RIMP or constipation compared with those without RIMP or constipation on follow
      up. Forty-eight percent of the patients with both recurrent constipation plus
      RIMP had manometric evidence of non-relaxing puborectalis syndrome compared with
      26% with RIMP but without constipation (P<0.05). Ten of the 14 patients (71%)
      with anxiety and/or depression complained of recurrent constipation after surgery
      compared with nine of the 26 patients (24%) with normal psychological profiles
      (P<0.01). Patients with a preoperative rectocele were more likely to suffer from
      recurrent constipation than those without rectocele (eight out of 15, 53.3% vs.
      seven out of 25, 28%; P<0.05). CONCLUSIONS: Primary excision of RIMP does not
      seem an effective treatment for obstructed defecation with predictive factors for
      an adverse outcome in terms of recurrence (RIMP and constipation) including the
      presence of preoperative non-relaxing puborectalis syndrome and a demonstrated
      anxiety or depression psychological profile. The technique of prolapsectomy does
      not seem to affect outcome.

PMID- 15947936
TI  - Short-term preoperative radiotherapy is a safe approach for treatment of locally
      advanced rectal cancer.
AB  - BACKGROUND AND AIMS: The Swedish Rectal Cancer Trial (SRCT) demonstrated that a
      short term regimen of high-dose preoperative radiotherapy (5x5 Gy) not only
      reduces the risk of local recurrence but also improves overall survival rate. An
      increase in postoperative mortality and morbidity has also been observed,
      however. We therefore evaluated early postoperative complications in patients
      treated with neoadjuvant radiotherapy for locally advanced rectal adenocarcinoma.
      PATIENTS/METHODS: Between 2000 and 2004, 85 patients with locally advanced rectal
      tumors were treated in our institution. Preoperative staging was based on CT scan
      and, in several cases, on endorectal ultrasonography. They were 55 men and 30
      women, with a median age of 68 years. They were retrospectively divided into two
      groups: Group A, which included 40 patients undergoing preoperative radiotherapy
      (25 Gy in five fractions) followed by surgery within 1 week, and Group B, which
      included 45 patients with rectal cancer receiving surgery immediately after
      diagnosis. Both groups were homogeneous regarding age, gender and preoperative
      stage of the disease. The two groups were compared for both technical
      difficulties during operation and rate of postoperative complications.
      RESULTS/FINDINGS: No postoperative deaths were recorded in either group. Low
      anterior resection with total mesorectal excision was performed in all group A
      patients, whereas eight patients in group B underwent abdominoperineal resection
      (P<0.05). Diverting stoma was performed in seven patients of group A and it was
      closed 3-6 months later on every occasion. Postoperative morbidity was not
      statistically significant between the two groups (40 vs 39%). The rate of
      postoperative hemorrhage, pelvic or abdominal wound infection, acute urinary
      infection, and delayed ileus was similar. The percentage of major anastomotic
      leak was also equivalent (5 vs 6.6%). INTERPRETATION/CONCLUSION: Short-term
      preoperative radiotherapy does not increase the rate of postoperative
      complications and is a safe therapeutic adjunct for the treatment of locally
      advanced rectal cancer.

PMID- 15947937
TI  - Solitary subglottic neurofibroma: a report of an unusual manifestation.
AB  - Neurofibromas of the larynx are extremely rare, especially in the subglottic
      part. Most of the patients with neurofibromas suffer from neurofibromatosis type
      1 (NF1, von Recklinghausen's disease), which is characterized by cafe-au-lait
      spots and neurofibromas of any type. We present a case of a solitary neurofibroma
      in the subglottic region that relapsed 4 years after the primary diagnosis. The
      clinical findings, histological results and therapy are discussed.

PMID- 15947938
TI  - Rare tumors of the internal auditory canal.
AB  - The study was performed to identify the incidence and histology of rare tumors
      with growth restricted to the internal auditory canal (IAC) that are different
      from vestibular schwannoma (VS). Furthermore, the question was addressed whether
      a preoperative diagnosis would be possible in these cases. A series of 351
      patients that were operated on for IAC tumors through a transtemporal or
      translabyrinthine approach was investigated retrospectively. Cases with a tumor
      entity other than VS were analyzed for symptoms, radiological diagnosis,
      intraoperative findings and postoperative histolopatology to determine if a
      differential diagnosis to the common VS can be established prior to surgery. In
      15 out of 351 cases (4.3%), uncommon processes of the IAC were determined by
      histology (6 lipomas, 3 hemangiomas, 2 neurofibromas, 2 menigiomas, 1 facial
      neuroma and 1 case of bilateral malignant lymphoma). The symptoms and the
      clinical manifestations were typical for patients with VS so that a preoperative
      differential diagnosis was not possible in the majority of cases. An analysis of
      the operation reports revealed that in 10 out of the 15 cases the surgeon
      suspected an unusual tumor of the IAC during surgery. The results of the present
      investigation suggest that rare lesions of the IAC can be expected in less than
      5% of the cases and that preoperative diagnosis of rare IAC tumors is difficult.
      Intraoperative findings such as adhesion to cranial nerves and consistency of the
      tumor often indicate unusual processes, but histological analysis of the removed
      tissue is essential for the definite diagnosis.

PMID- 15947939
TI  - Photodynamic therapy with verteporfin for choroidal neovascularization associated
      with angioid streaks.
AB  - BACKGROUND: Choroidal neovascularizations (CNV) is the major cause of significant
      visual loss in patients with angioid streaks. We evaluated the functional and
      morphological outcome of Verteporfin photodynamic therapy (PDT) in the treatment
      of these patients. METHODS: This was a retrospective study in two tertiary
      referral centres over a 3-year period. Examinations included visual acuity
      assessment with ETDRS charts, binocular fundoscopy and fluorescein angiography.
      PDT was performed with standard parameters; earlier retreatments were feasible in
      active CNV. RESULTS: Fifteen eyes from 12 patients (9 male, 3 female) with a
      follow-up of 12-50 months (mean 26.1, median 19 months) were included. Five
      lesions were extra-or juxtafoveal and ten were subfoveal. Baseline visual acuity
      was between 20/63 and 20/16 (mean 20/32, median 20/32). Eyes were treated with
      two to eight treatments of PDT (mean 4.2, median 4). Treatment intervals were
      between 5.6 and 72 weeks (mean 12.1, median 9.2 weeks). At the 1-year follow-up,
      visual acuity was below 20/200 in 27% (4/15), 20/200 or better in 73% (11/15) and
      20/63 or better in 47% (7/15) with an improvement of >3 lines in 13% (2/15), no
      change in 27% (4/15) and a decrease of >3 lines in 60% (9/15). At the final
      follow-up examination, all lesions were located subfoveally. Visual acuity was
      below 20/200 in 47% (7/15), 20/200 or better in 53% (8/15) and 20/63 or better in
      13% (2/15) with a change in visual acuity between +2 and -18 lines (mean -9
      lines, median -8 lines). No change was noted in 7% (1/15) and a decrease of >3
      lines in 93% (14/15) of eyes. The maximum measured greatest linear dimension of
      the lesion during the follow-up varied between 2400 microm and 6200 microm (mean
      3680 microm, median 3600 microm) with an increase in the lesion size compared
      with baseline values between +/-0 microm and +3700 microm (mean+1420 microm,
      median+1500 microm). CONCLUSION: PDT for CNV associated with angioid streaks
      seemed to slow down but not prevent the progression of the disease and associated
      visual loss. Further modifications of the treatments parameters or a combination
      with other therapeutical options seem warranted for a more effective treatment of
      these lesions.

PMID- 15947940
TI  - Levels of pentosidine in the vitreous of eyes with proliferative diabetic
      retinopathy, proliferative vitreoretinopathy and retinal detachment.
AB  - BACKGROUND: Advanced glycosylation end products (AGEs) are thought to play an
      important role in the pathophysiology of diabetes. Particularly, these products
      have been implicated in the pathogenesis of proliferative diabetic retinopathy.
      The majority of these products are formed from a vast range of precursor
      molecules, the variable chemical nature of which contributes to AGE
      heterogeneity. There is a growing population of structurally defined AGE adducts
      such as pyrraline, pentosidine, CML and crossline that have been found to be
      elevated in diabetic tissues. In the present study, the levels of the
      glycoxidation product pentosidine were determined in vitreous samples obtained
      during vitrectomy from eyes with proliferative diabetic retinopathy (PDR),
      proliferative vitreoretinopathy (PVR), and retinal detachment (RD). Samples from
      cadaveric control eyes were also included in the study. The levels of pentosidine
      were compared among the groups. METHODS: Seventy-three vitreous samples were
      collected from eyes undergoing vitrectomy for PDR (n=33), PVR (n=28) and RD
      (n=12). Eighteen samples from cadaveric control eyes were also included in the
      study. A modified Bradford's method was used to assay protein content, and
      vitreous levels of pentosidine were determined by high-performance liquid
      chromatography after acid hydrolysis and pretreatment with SP-Sephadex.
      Statistical analyses were performed using a two-sided Mann-Whitney U test.
      RESULTS: The levels of pentosidine [median (interquartile range)] were 0.92 (0.55
      1.26) pmol/mg of protein in the PDR cases, 1.12 (0.46-1.80) pmol/mg of protein in
      PVR, and 1.02 (0.24-1.44) pmol/mg of protein in RD. In the cadaveric control eyes
      pentosidine levels were 0.97 (0.68-1.30) pmol/mg of protein. The pentosidine
      levels of the four groups did not differ significantly. CONCLUSIONS: The levels
      of the glycoxidation product pentosidine (expressed as pmol/mg of protein) in the
      vitreous of eyes with PDR do not differ significantly from those in the vitreous
      of eyes with PVR, RD or cadaveric control eyes. Although these results do not
      refute the findings of previous studies that evaluated globally total AGE levels
      and the existence of diabetic vitreopathy, further investigation is needed to
      fully understand their relevance in this multifactorial disorder.

PMID- 15947941
TI  - An optimized protocol for detection of E. coli beta-galactosidase in lung tissue
      following gene transfer.
AB  - Staining by 5-bromo-4-chloro-3-indolyl-beta-D: -galactopyranoside (X-gal)
      typically detects activity of E. coli beta-galactosidase (beta-gal) in transduced
      tissues that express the LacZ reporter gene. In lung tissue from mice that
      received beta-galactosidase-expressing adeno-associated virus (AAV) vectors via
      intranasal inhalation, we observed only a low frequency of positive cells after X
      gal staining in contrast to other reporter genes, such as alkaline phosphatase or
      green fluorescent protein. In this study, we systematically tested a number of
      parameters to improve the sensitivity of X-gal staining in lungs transduced with
      beta-galactosidase-expressing AAV2/5 vectors. We observed that the use of nuclear
      targeted LacZ instead of cytoplasmic LacZ as the reporter gene substantially
      increases the number of positive cells after X-gal staining. The pH of the
      staining solution determines staining sensitivity and background staining with pH
      7.0 resulting in high sensitivity and no background levels. Glutaraldehyde at
      0.2% or 0.5% in PBS as fixative provides optimal results for X-gal staining. The
      alternative substrate, Bluo-gal, showed no improvement compared with X-gal but
      instead caused nonspecific background staining. We further stained intact fixed
      lungs with X-gal and processed them for paraffin embedding or cryosectioning,
      resulting in equal staining intensities. However, en bloc staining of intact
      tissues resulted in the absence of positive cells within deeper-located lung
      areas.

PMID- 15947942
TI  - The transverse coloplasty pouch.
AB  - BACKGROUND: The introduction of the total mesorectal excision (TME) and the use
      of modern staplers have improved outcome and increased the rate of sphincter
      preserving low anterior resections in rectal cancer. Consequently, the interest
      in functional results after rectal reservoir reconstruction increased
      significantly. METHODS: A review of the current literature was conducted on the
      development of colon pouch procedures with a particular focus on the transverse
      coloplasty pouch compared with the colon J-pouch and other current techniques of
      reconstruction after TME such as the side-to-end anastomosis. RESULTS: The colon
      J-pouch (CJP) became the "gold standard" for rectal reservoir reconstruction
      owing to better early functional results compared with the straight coloanal
      anastomosis (CAA). However, 30% of the patients with CJP faced late evacuation
      problems requiring the chronic use of enemas or laxatives. This rate could be
      decreased by shortening the limb of the CJP from 8-10 to 5-6 cm, but the late
      evacuation problems remained in approximately 10% of the patients. An overview of
      the current knowledge on technical and functional aspects as well as indications
      and results of the transverse coloplasty pouch (TCP) is presented. CONCLUSION:
      The TCP was developed to provide early functional results comparable to the CJP
      while avoiding the late evacuation problems. Functional results after TCP, small
      colon J-pouch and side-to-end anastomosis are similar. Evacuation problems after
      TCP have not been reported.

PMID- 15947944
TI  - Portal capillary C4d deposits and increased infiltration by macrophages indicate
      humorally mediated mechanisms in acute cellular liver allograft rejection.
AB  - Almost no data exist concerning the role of antibody-mediated mechanisms in human
      acute cellular liver allograft rejection (ACR). Therefore, the aim of this study
      was to determine whether ACR is associated with depositions of complement split
      products and increased infiltration by B-lymphocytes, plasma cells and
      macrophages. A total of 35 liver biopsy specimens (ACR n=22, controls n=13) were
      analyzed by immunohistochemical single and double staining. The average numbers
      of CD 20(+), CD 38(+) and CD 68(+) cells per portal tract were established while
      the presence of C4d and C3d deposits was evaluated semiquantitatively.
      Significantly greater numbers of CD 20(+) (P=0.029) and CD 38(+) (P=0.014) cells
      were found in the ACR specimens than in the control specimens. Additionally, 50%
      of patients diagnosed with ACR showed C4d deposits along portal capillaries,
      which was associated with a significantly increased portal infiltration by
      macrophages (P=0.007). Taken together these results support the involvement of
      humorally mediated mechanisms in some cases of ACR.

PMID- 15947943
TI  - Significance of inducible nitric oxide synthase expression in benign and
      malignant breast epithelium: an immunohistochemical study of 151 cases.
AB  - The role of calcium independent inducible nitric oxide synthase (iNOS) in breast
      carcinoma is controversial, and the implications of iNOS expression on prognosis
      are not known. In this study, we aimed to investigate the significance of
      immunohistochemical iNOS expression in 100 invasive ductal carcinomas. In
      addition, 11 normal breast tissues, 20 cases of usual ductal hyperplasias (UDHs)
      and 20 fibroadenomas were included. We found that 78% of malignant and 75% of
      benign cases showed iNOS immunoreactivity. However, the intensity and the
      quantity of iNOS expression were significantly higher in the cancer group when
      compared with benign breasts (P<0.001), suggesting a role of iNOS in breast
      carcinogenesis. We were unable to show a correlation between iNOS expression and
      tumor grade, axillary lymph node status, and estrogen receptor expression. In 50
      axilla negative cases having 5--12 years follow-up, disease free survival (DFS)
      rate was significantly lower in cases showing strong iNOS expression (P=0.05). As
      strong iNOS expression was correlated with short DFS, we concluded that further
      studies would be necessary to elucidate if iNOS expression might be a useful
      prognostic marker in breast carcinoma, especially in the axilla negative group.

PMID- 15947945
TI  - Cyclooxygenase-2 in normal, hyperplastic and neoplastic follicular cells of the
      human thyroid gland.
AB  - This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in
      follicular cells of the human thyroid. COX-2 expression was studied
      immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was
      confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2
      expression was observed in five cases (17.2%) of normal follicular cells and in
      one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more
      frequently than follicular adenoma (93.4% vs 21.1%) (p<or=0.001). A higher
      percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison
      with all papillary carcinomas (p<or=0.05). However, we could not establish any
      relationships among COX-2, patients' ages or lymph node metastases in papillary
      carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated
      carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is
      not always useful as a marker of malignancy. Our results suggest that COX-2 plays
      a role in progression of all thyroid carcinomas, but in papillary carcinomas,
      seems more important only in the early stages. COX-2 expression in the
      undifferentiated carcinoma deserves special consideration due to its prognosis
      and to the fact that selective COX-2 inhibitors were found to enhance tumour
      response to radiation in some studies.

PMID- 15947946
TI  - Thyroid transcription factor 1 expression in cystic lesions of the neck: an
      immunohistochemical investigation of thyroglossal duct cysts, branchial cleft
      cysts and metastatic papillary thyroid cancer.
AB  - Cervical metastases of papillary thyroid cancer (PTC) are of particular
      diagnostic importance, because they can mimic branchiogenic cysts clinically and
      histopathologically when undergoing cystic change. Immunohistochemical stains for
      thyroid transcription factor 1 (TTF-1), which are positive in thyroid cancers,
      are reported to be valuable in establishing diagnosis. However, TTF-1 may also be
      expressed in dysontogenetic cysts of the neck. Therefore, immunohistochemical
      stains for TTF-1 and thyroglobulin (TG) were performed on each of the ten
      thyroglossal duct cysts, branchial cleft cyst and lymph node metastasis of PTC.
      Five in ten cases of thyroglossal duct cysts were positive for TTF-1, but all
      were negative for TG. One of the ten branchial cleft cysts stained for TTF-1,
      while all cases were negative for TG. All ten cases of lymph node metastases of
      PTC showed positive for TTF-1, nine of which were positive for TG. Since a
      positive immunostaining for TTF-1 in cystic lesions of the neck was not only
      found in metastases of PTC, but also in non-malignant branchiogenic cysts,
      additional investigations, e.g. an immunostaining for TG, should be added in
      difficult cases.

PMID- 15947947
TI  - Early atherosclerotic lesions in infancy: role of parental cigarette smoking.
AB  - Cigarette smoking is associated with an increased incidence of atherosclerotic
      diseases. The aim of this study was to examine the progression of the pre
      atherosclerotic lesions previously observed by us in coronary arteries of fetuses
      of smoker mothers and in infants with smoker parents. We examined the coronary
      arteries of 34 infants, aged 1-36 months, and the histological and biological [c
      fos, proliferating cell nuclear antigen (PCNA), and apoptosis] features of the
      early atherosclerotic lesions. In 17 infants (50%), at least one parent smoked,
      generally more than five cigarettes a day. In 18 cases (53%), we observed
      variable thickening of the coronary walls from pre-atherosclerotic lesions to
      juvenile atherosclerotic plaques, related to parental smoking habit. This
      morphological progression of the lesions was accompanied by a sequence of
      biological changes in the smooth muscle cells of the tunica media. We suggest
      that the oxidants present in the gas phase of the parental cigarette smoke pass
      through the endothelium and induce at first the c-fos gene activation and
      subsequently the PCNA positivity, that is, a proliferative process.

PMID- 15947948
TI  - Hemosiderotic fibrohistiocytic lipomatous lesion: clinical correlation with
      venous stasis.
AB  - Hemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a recently proposed
      lipomatous entity. HFLL was originally suggested to be a benign reactive lesion
      arising due to an antecedent trauma. We report two patients with HFLL who also
      suffered from chronic vein insufficiency due to varicose involving deep veins of
      the low limbs. Both patients were middle-aged women with solitary, poorly
      circumscribed subcutaneous lesions on the lower extremities. Histopathological
      examination revealed typical features of HFLL. We think that the consistent
      clinical features such as advanced age, female sex predilection, and specific
      location along with distinctive histopathological features allow the suggestion
      that impaired blood circulation, to wit, venous stasis is involved in the
      pathogenesis of HFLL. We hypothesize that the proliferation of spindled
      fibroblastic and myofibroblastic cells and capillaries, erythrocyte
      extravasation, and hemosiderin deposition with lipomatous tissue of HFLL may
      simply represent an exaggerated tissue response to venous stasis in which
      elevated venous and capillary pressures, oxygen saturation, and edema stimulate
      the proliferation of the above mentioned elements and lead to erythrocyte
      extravasation. A similar histopathological pattern is seen in acroangiodermatitis
      of Mali and vascular transformation of lymph node sinuses, and these conditions
      are also associated with impaired blood circulation.

PMID- 15947949
TI  - Standardised fluorescence in situ hybridisation in cytological and histological
      specimens.
AB  - Fluorescence in situ hybridisation (FISH) has gained major impact in the
      detection of chromosomal aberrations. The application of FISH, however, is
      hampered due to complicated protocols. We therefore designed a FISH protocol that
      allows the fast and reliable application on cytological and histological
      specimens. Cytological and histological specimens of bone marrow, lymph nodes,
      liver and breast were analysed with 14 sets of centromere or locus-specific
      probes. A pretreatment of enzymatic digestion and microwave heating with the same
      incubation times for all specimens and probes used was performed. Hybridisation
      efficiency was proved by calculating the thresholds for monosomy, trisomy and
      translocations. Values in cytological specimens reached 9.0, 3.9 and 4.6%,
      respectively. In histological sections, values of 6.4% were seen for aneusomy and
      3.1% for translocations. However, values for monosomy reached 20.5% in bone
      marrow and 61.8% in liver tissues due to cutting artifacts. In bone marrow with
      acute myeloid leukaemias, lymph nodes with follicular and mantle cell lymphomas,
      breast carcinomas and liver cell carcinomas, FISH confirmed aberrations already
      found using conventional cytogenetics. The protocol shown here is easy to perform
      and can be used with cytological and histological specimens. Moreover, with
      "hands on" time of less than 2 h, FISH can also be used for daily routine
      purposes.

PMID- 15947950
TI  - Lymphoepithelioma-like carcinoma of the breast. Report of a case with the first
      electron microscopic study and review of the literature.
AB  - Lymphoepithelioma-like carcinoma (LELC) is a tumor which occurs outside the
      nasopharynx and has morphological features identical to nasopharyngeal
      lymphoepithelioma. LELC of the breast (LELC-B) is uncommon, and its resemblance
      to medullary carcinoma of the breast (MC-B) obscures distinction between these
      two tumors. We report a case of LELC-B occurring in a 47-year-old woman. The
      tumor consisted of multinodules without circumscription. The tumor cells mainly
      exhibited loose clusters being permeated by numerous lymphocytes. The tumor cell
      clusters showed inconspicuous margins, which were far from syncytial patterns.
      The epithelial nature of the tumor cells was demonstrated by positivity for
      epithelial membrane antigen, AE1/AE3 and CAM5.2. Furthermore, glandular
      differentiation of the tumor cells was confirmed using electron microscopy for
      the first time. Epstein-Barr virus (EBV) was not detected using either in situ
      hybridization or polymerase chain reaction. These findings, together with former
      reports of LELC-B, suggest that the distinction between LELC-B and MC-B depends
      on whether circumscription and syncytial growth patterns exist. The other
      findings, including absence of EBV and immunohistochemical aspects of the tumor
      cells, are not considered different thus far. Although the prognosis of LELC-B is
      thought to be favorable, which is also similar to MC-B, distant metastasis was
      detected in the present case. To confirm the clinicopathological entity of these
      two tumors, it is important to recognize the difference between LELC-B and MC-B.

PMID- 15947951
TI  - Direct fermentation of potato starch wastewater to lactic acid by Rhizopus oryzae
      and Rhizopus arrhizus.
AB  - The biochemical kinetic of direct fermentation for lactic acid production by
      fungal species of Rhizopus arrhizus 3,6017 and Rhizopus oryzae 2,062 was studied
      with respect to growth pH, temperature and substrate. The direct fermentation was
      characterized by starch hydrolysis, accumulation of reducing sugar, and
      production of lactic acid and fungal biomass. Starch hydrolysis, reducing sugar
      accumulation, biomass formation and lactic acid production were affected with the
      variations in pH, temperature, and starch source and concentration. A growth
      condition with starch concentration approximately 20 g/l at pH 6.0 and 30 degrees
      C was favourable for both starch saccharification and lactic acid fermentation,
      resulting in lactic acid yield of 0.87-0.97 g/g starch associated with 1.5-2.0
      g/l fungal biomass produced in 36 h fermentation. R. arrhizus 3,6017 had a higher
      capacity to produce lactic acid, while R. oryzae 2,062 produced more fungal
      biomass under similar conditions.

PMID- 15947952
TI  - Non-invasive ventilation for cancer patients with life-support techniques
      limitation.
AB  - GOALS OF WORK: The study was conducted to determine the usefulness and efficacy
      of non-invasive ventilation (NIV) in cancer patients with "life-support
      techniques limitation" admitted for an acute respiratory distress, in terms of
      intensive care unit (ICU) and hospital discharges. PATIENTS AND METHODS: A total
      of 18 consecutive cancer patients (17 with solid tumours and one with
      haematological malignancy) with "life-support techniques limitation" in acute
      respiratory failure and who benefited from NIV were included. NIV was provided
      with a standard face mask by the BiPAP Vision ventilator (Respironics Inc.).
      Variables related to the demographic parameters, SAPS II score, cancer
      characteristics, intensive care data and hospital discharge were recorded. MAIN
      RESULTS: Complications leading to NIV were hypoxemic respiratory failure in 11
      patients and hypercapnic respiratory failure in seven. Total median duration of
      NIV was 29 h. NIV was applied during a median of 2.5 days with a median of 16 h
      per day. Total median ICU stay was 7 days (range 1-21). Fourteen and ten patients
      were discharged from ICU and from hospital, respectively. CONCLUSION: NIV appears
      to be an effective ventilation support for cancer patients with "life-support
      techniques limitation".

PMID- 15947953
TI  - Palliative care for patients with cancer: what are the educational needs of
      community pharmacists?
AB  - AIMS: The objective of this study was to determine the educational needs of
      community pharmacists in Australia related to palliative cancer care, to guide
      the development of an online educational program for pharmacists. METHODS:
      Questionnaires were posted to a random sample of community pharmacies in
      Australia. The questionnaire sought information pertaining to pharmacists':
      demographics; educational needs by rating the importance of learning more about
      18 palliative cancer care topics and self-perceived level of knowledge of them;
      preference for format(s) for the program; willingness to participate in the
      program; and perception regarding their practice of palliative cancer care.
      Results were analysed using Statistical Package for the Social Sciences (SPSS)
      version 11.5 software. MAIN RESULTS: A questionnaire return rate of 10.3% was
      achieved. The characteristics of respondents were reflective of community
      pharmacy practice in Australia when compared with the latest available labour
      force figures by the Australian Institute of Health and Welfare. Pharmacists
      rated all 18 topics as "important/essential", and their level of knowledge of
      them as "poor/good". Pharmacists preferred information provided in these formats:
      text (89.8%), case studies (80.6%) and multi-choice questions (69.4%). Most
      pharmacists (85.2%) indicated that they would participate in the program. The
      majority of pharmacists (71.3%) reported that they deliver palliative cancer care
      services; usually less-than-monthly (24.1%) or weekly (21.3%). CONCLUSIONS:
      Educational needs of community pharmacists in palliative cancer care were
      identified. The information gathered will assist in guiding the development of an
      online educational program for pharmacists to improve their knowledge and skills
      in palliative cancer care.

PMID- 15947955
TI  - Infectious complications in patients with hematological malignancies consulted by
      the Infectious Diseases team: a retrospective cohort study (1997-2001).
AB  - In order to identify the characteristics of patients with hematological
      malignancies (HM) in the presence/suspicion of any accompanying infectious
      disease, and to find the predictors of mortality in this group, hospital charts
      of patients with HM consulted by the Infectious Diseases (ID) team for
      signs/symptoms of any infection between January 1, 1997 and December 31, 2001
      were retrospectively reviewed. A total of 1,132 consultations were done for 641
      patients: 59.4% of the patients were male and the mean (+/-standard deviation)
      age of the study participants was 47.9+/-1.4 years. The most common underlying
      diseases were non-Hodgkin's lymphoma (30.9%), acute myelogenous leukemia (26.2%),
      and multiple myeloma (10.9%). Clinically and microbiologically documented
      infections and fever of unknown origin were observed in 43.3%, 38.1%, and 18.5%
      of the participants, respectively. Bloodstream infections were detected in 134
      episodes (20.9%): 56.5% were caused by gram-negative microorganisms. In logistic
      regression analysis, the presence of pneumonia (OR 7.56, 95% CI 4.84-12.486),
      invasive fungal infection (OR 4.12, 95% CI 1.78-9.55), relapse or recent
      diagnosis of the underlying disease (OR 2.82, 95% CI 1.53-5.21) and neutropenia
      (OR 2.70, 95% CI 1.70-4.31) were identified as statistically significant
      predictors of mortality.

PMID- 15947954
TI  - Use of complementary and alternative medicine by patients with urologic cancer: a
      prospective study at a single Japanese institution.
AB  - OBJECTIVES: We prospectively evaluated the prevalence and predictors of
      complementary medicine (CAM) use among Japanese patients with urologic cancer 1
      year after diagnosis. PATIENTS AND METHODS: A total of 349 patients with newly
      diagnosed urologic cancer answered a self-administered questionnaire on CAM use 1
      year after diagnosis. General-health-related quality of life (GHQL) of the
      patients was also assessed at diagnosis and 1 year after diagnosis using the
      Medical Outcome Study Short Form-36 (SF-36). The overall prevalence, types of CAM
      used, and costs of CAM were assessed. The effects of several variables including
      GHQL at baseline and 1 year after treatment on the prevalence of use of CAM were
      evaluated. RESULTS: A total of 164 respondents (47%) admitted using some type of
      CAM, of which 73 (45%) had used multiple types. "Health food," in particular
      extract from Agaricus blazei, was the most common type of CAM used. CAM users had
      significantly lower scores for social function, general health perception, and
      vitality domains than CAM non-users 1 year after diagnosis. This tendency was
      more marked in users of multiple types of CAM. CONCLUSIONS: "Health food,"
      including extract from A. blazei, was the most commonly used CAM in Japan. The
      prevalence of CAM use did not differ between patients with prostate cancer and
      those with urologic cancer other than prostate cancer. CAM users, especially
      those who used multiple types of CAM, had lower GHQL scores than non-users of
      CAM.

PMID- 15947956
TI  - Effect of fluconazole antifungal prophylaxis on oral mucositis in head and neck
      cancer patients receiving radiotherapy.
AB  - GOAL OF WORK: The aim of the study is to evaluate the effect of fluconazole
      antifungal prophylaxis on the severity of mucositis in head and neck cancer
      patients receiving radiotherapy. PATIENTS AND METHODS: Sixty-three patients, with
      malignant head and neck tumor, eligible to receive radiotherapy, entered the
      study. Thirty-four patients (group A) received 100 mg/day of fluconazole
      prophylaxis during radiotherapy and were compared with 29 patients, who received
      radiotherapy alone (group B). The two groups were similar in terms of patients
      and radiotherapy characteristics. Smear to test for Candida carriage was taken
      before and after radiotherapy. Oral candidiasis was diagnosed using the criteria
      described before. Oral mucositis was recorded according to EORTC/RTOG criteria.
      MAIN RESULTS: A significant reduction of severe mucositis at the end of
      radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017)
      was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a
      significant reduction of Candida carriage of 40.7% (p=0.001). CONCLUSION:
      Fluconazole prophylaxis showed a significant beneficial impact on the severity of
      mucositis and on radiotherapy interruptions in this group of patients. The
      current study provides data on the build of a randomized controlled trial on the
      effect of fluconazole prophylaxis on treatment schedule and quality of life of
      the patients during head and neck radiotherapy.

PMID- 15947957
TI  - The mycorrhizal community in a forest chronosequence of Sitka spruce [Picea
      sitchensis (Bong.) Carr.] in Northern England.
AB  - Demography and fungal diversity of the belowground ectomycorrhizal community in a
      chronosequence of Sitka spruce [Picea sitchensis (Bong.) Carr.] in
      Northumberland, Northern England, were analysed; mycorrhizal root samples were
      taken from 6-, 12-, 30- and 40-year-old stands, and fungal fruiting bodies were
      collected in autumn to complement the survey. Naturally germinated seedlings less
      than 1 year of age (taken from the 30-year-old stand) were also examined. A total
      of 118,000 mycorrhizal root tips were extracted from 40 soil cores (ten per age
      class) and from the complete root systems of 25 seedlings and separated into
      active and senescent root tips according to their morphology and anatomy. Active
      tips were distinguished according to their mycobionts which were characterised
      and identified microscopically. Although almost 100% of all fine roots were
      mycorrhizal, EM fungal diversity throughout the chronosequence was low,
      consisting of a total of 16 species of which three were only found as fruiting
      bodies. Of the six mycobionts found most regularly below ground, Tylospora
      fibrillosa was the most common, colonising about 70% of all root tips and more
      than 90% of those of seedlings and young trees. Root density and mycorrhizal
      diversity increased, but percentage of vital root tips decreased with increasing
      tree age, levelling off in the 30- and 40-year-old stand. Among the five
      subdominant fungal species, Dermocybe crocea was found to have its peak of
      distribution in the 12-year-old stand and Russula emetica, Lactarius rufus,
      Hymenoscyphus ericae agg. and the unidentified Piceirhiza sulfo-incrustata in the
      30- and 40-year-old stands. The possible correlations between the mycorrhizal
      community structure and biotic and abiotic factors are discussed.

PMID- 15947958
TI  - Literature review regarding the methodology of assessing third nerve paresis
      associated with non-ruptured posterior communicating artery aneurysms.
AB  - The association of third cranial nerve palsy subsequent to an enlarging posterior
      communicating artery (P-Com A) aneurysm has been well described. In our current
      communication, we review the relevant literature and propose a classification
      system for the severity of the third cranial nerve palsy, correlating it to the
      postoperative recovery. Our four grade scale (I-IV) included the degree of the
      levator palpebrae muscle paresis, the presence of pupillary reaction and the
      impairment of the third nerve mediated extraocular muscle movement. We evaluated
      five patients with third nerve palsy secondary to non-ruptured, P-Com A aneurysm.
      Patients were re-evaluated at 2, 4, 8, 24 weeks postoperatively. Four of the five
      patients had complete recovery within 4-8 weeks after surgery. One patient had
      grade II third nerve paresis and complete resolution of the third nerve symptoms
      within 4 weeks, whereas three patients with grade III and IV had complete
      resolution 4-8 weeks after surgery. The fifth patient, with grade IV paresis, had
      minimal (grade III) improvement 6 weeks after surgery, and incomplete recovery
      (grade I) 6 months postoperatively. Our simple grading system of third nerve
      palsy associated with P-Com A aneurysms, can be a helpful tool for the initial
      evaluation and for the monitoring of recovery in these patients.

PMID- 15947960
TI  - Ability of the Hershberger assay protocol to detect thyroid function modulators.
AB  - In vivo screening methods for detection of thyroid function modulators are now
      under development in many research laboratories. We assessed the applicability of
      the Hershberger assay protocol to screen for thyroid function modulators. In
      experiment 1, castrated male BrlHan WIST@Jcl (GALAS) rats were administered a
      potent thyroid peroxidase inhibitor, 3-amino-1,2,4-triazole (AT), in doses of 0,
      40, 200, and 1,000 mg/kg/day with gravimetric endpoint, and in experiment 2,
      castrated and intact male rats were administered in doses of 0, 40, and 200
      mg/kg/day, with quantification of the extent of hypertrophy of the thyroid
      epithelium, to assess the effects of castration, by gavage to 8-week-old for 10
      consecutive days. At necropsy of both experiments, the thyroid glands and
      hypophysis were collected and fixed with 10% neutral-buffered formalin. To avoid
      crushing during weighing because of their fragility, the thyroid glands and
      hypophysis were weighed approximately 24 h after fixation with 10% neutral
      buffered formalin. All animals were sacrificed approximately 24 h after the final
      dose. In experiment 2, the thyroid glands of all animals were stained with
      hematoxylin and eosin for histological examination and morphometry of follicular
      epithelial height. In experiment 1, absolute and relative thyroid weights in all
      of the AT groups were statistically increased in a dose-dependent manner,
      regardless of the testosterone propionate (TP)-injection. In experiment 2, the
      results showed a significant increase in thyroid weight in the 200 mg/kg groups
      of both castrated and intact rats. Hypophyseal weight was unaltered by AT, but
      comparison of vehicle-treated groups showed that the hypophyseal weight of the
      castrated rats was greater than that of the intact rats. Enlarged thyroid glands
      were observed in the AT-treated rats at necropsy. Histological examination of the
      thyroid glands of all the AT-treated animals showed hypertrophy and hyperplasia
      of the follicular epithelial cells, and the height of follicular epithelium of
      the thyroid glands increased in a dose-dependent manner in both the castrated and
      intact rats. In experiment 1, assessment of the (anti-) androgenic action of AT
      in seminal vesicle weight revealed a significant increase in the 200 and 1,000
      mg/kg + TP groups in a dose-dependent manner. These results suggest that the
      effect of AT can be detected by the Hershberger assay 10-day administration
      protocol and may be useful for screening for thyroid function modulators
      regardless of whether the animals have been castrated.

PMID- 15947959
TI  - Isolation and characterization of solvent-tolerant Pseudomonas putida strain T
      57, and its application to biotransformation of toluene to cresol in a two-phase
      (organic-aqueous) system.
AB  - Pseudomonas putida T-57 was isolated from an activated sludge sample after
      enrichment on mineral salts basal medium with toluene as a sole source of carbon.
      P. putida T-57 utilizes n-butanol, toluene, styrene, m-xylene, ethylbenzene, n
      hexane, and propylbenzene as growth substrates. The strain was able to grow on
      toluene when liquid toluene was added to mineral salts basal medium at 10-90%
      (v/v), and was tolerant to organic solvents whose log P(ow) (1-octanol/water
      partition coefficient) was higher than 2.5. Enzymatic and genetic analysis
      revealed that P. putida T-57 used the toluene dioxygenase pathway to catabolize
      toluene. A cis-toluene dihydrodiol dehydrogenase gene (todD) mutant of T-57 was
      constructed using a gene replacement technique. The todD mutant accumulated o
      cresol (maximum 1.7 g/L in the aqueous phase) when cultivated in minimal salts
      basal medium supplemented with 3% (v/v) toluene and 7% (v/v) 1-octanol. Thus, T
      57 is thought to be a good candidate host strain for bioconversion of hydrophobic
      substrates in two-phase (organic-aqueous) systems.

PMID- 15947961
TI  - Spinal cord control of ejaculation.
AB  - Ejaculation is a reflex mediated by a spinal control center, referred to as a
      spinal ejaculation generator. During intercourse, the spinal ejaculation
      generator integrates the sensory inputs that are necessary to trigger
      ejaculation. At the time of ejaculation, it coordinates the sympathetic,
      parasympathetic, and somatic outflow to induce the two phases of ejaculation,
      i.e. emission and expulsion. It also provides the brain with signals related to
      the occurrence of ejaculation. Experimental and clinical data evidenced that
      these functions were devoted to neurons located in the lumbosacral cord. We
      recently characterized a population of spinothalamic neurons in the lumbar spinal
      cord of male rats (LSt cells) that constitutes an integral part of the spinal
      ejaculation generator. LSt cells send projections to the autonomic nuclei and
      motoneurons involved in the emission and expulsion phase, and they receive
      sensory projections from the pelvis. LSt cells are activated with ejaculation,
      but not following other components of sexual behavior, and lesions of LSt cells
      completely ablate ejaculatory function. These data support a pivotal role for the
      LSt cells in the control of ejaculation.

PMID- 15947962
TI  - Cognitive and partner-related factors in rapid ejaculation: differences between
      dysfunctional and functional men.
AB  - Despite the high prevalence of rapid ejaculation in community samples, there is
      still a paucity of data on cognitive and other relevant aspects of the subjective
      experience of premature ejaculation (PE) patients and their functional
      counterparts. Therefore, the main aim of this study was to expand our
      understanding of the complex nature of rapid ejaculation disorders by providing a
      detailed characterization of ejaculatory patterns, behavioral aspects, cognitive,
      and partner-related factors in a sample of unselected PE patients compared to a
      group of functional men. To explore the areas that might differentiate PE men
      from their sexually functional counterparts, a multidimensional self-administered
      questionnaire, the PEQuest, was created. This 36-item instrument addresses a
      number of domains relevant to ejaculatory function and dysfunction such as
      ejaculatory latencies and ejaculatory control, cognitions and feelings during
      sexual intercourse, factors interfering with ejaculatory control, techniques to
      delay ejaculation, and partnership factors. A total of 45 PE patients (mean age:
      41.8 years) and 72 non-patients (mean age: 37.1 years) were included. The results
      show significant group differences in the majority of PEQuest domains. In the
      functional group, an average intravaginal latency time of 12.8 min (median: 10
      min) was reported compared to 3.7 min (median: 2 min) in the patient group with
      87% of PE patients ejaculating within 2 min and 100% within 5 min after
      penetration. In their subjective experience in sexual situations, PE patients
      were totally preoccupied with thoughts about controlling their orgasm, with the
      anxious anticipation of a possible failure, and thoughts about keeping their
      erection while the inner experience of functional men is focused on sexual
      arousal and sexual satisfaction. The factors that maximally impede the control of
      ejaculation are similar for both groups, but functional men normally succeed in
      adapting their sexual behavior to these factors whereas PE men fail in their
      efforts. Regarding partner-related factors, PE patients felt less secure and
      experienced with respect to female sexuality than their functional counterparts,
      and more often reported a discrepancy between their own limited experience and
      the more extensive sexual experience of their partner. In conclusion, a number of
      salient differences in ejaculatory behavior, cognitive-affective patterns, and
      partner-related factors between PE patients and functional men could be
      delineated in this study, indicating that chronic rapid ejaculation is a serious
      disorder with a profound impact on the man's life and his partnership.

PMID- 15947963
TI  - [Fuchs uveitis syndrome--heterochromia is no "conditio sine qua non"].
AB  - Fuchs uveitis syndrome (FUS) is typically a unilateral, chronic, low-grade
      inflammation of the anterior segment which manifests in young adulthood. It is
      underdiagnosed because of its variable clinical spectrum. Although it can mimic
      various forms of anterior uveitis, it is important to make the correct diagnosis,
      based on clinical grounds, because both the management and prognosis differ from
      those of other uveitides. While its etiology remains unknown, it is possible that
      the disease has multiple causes that lead through different pathogenic mechanisms
      to the same clinical entity. Although many patients do not require treatment, it
      is not a benign condition, as often perceived. The high incidence of glaucoma
      makes it mandatory that all patients with FUS should be screened at regular
      intervals, even if they are not being actively treated and are relatively
      asymptomatic.

PMID- 15947964
TI  - [Transpupillary thermotherapy (TTT) for uveal melanomas. Long term results of a
      single TTT with an adapter for a conventional infrared laser].
AB  - BACKGROUND: An increasing number of orbital recurrences after TTT have been
      reported; the aim of our paper was to present our long-term results after a
      maximum follow-up of 8 years and 2 months. PATIENTS AND METHOD: Among 18 eyes, 10
      tumors were classified as small, and 8 as medium sized (with a maximum prominence
      of 5.6 mm): 5 melanomas had a juxtapapillary location, 6 a macular (or
      juxtamacular) location, and 7 were located in the midperiphery of the fundus.
      RESULTS: After a median follow-up of 7 years in seven tumors a complete
      regression (scar formation) could be achieved, and in six a partial regression
      (with a maximum residual prominence of 2.9 mm) could be seen. In three patients a
      recurrence was treated either by another TTT or a Ruthenium-106 plaque; in
      another two recurrences, enucleation had to be performed. In none of the cases
      has an orbital recurrence occurred so far. CONCLUSION: To prevent recurrences,
      adequate technique and appropriate selection of patients are mandatory in our
      opinion (no tumors higher than 3 mm). The higher the tumor prominence, the
      greater the chance of recurrences. Amelanotic melanomas and macular melanomas
      seem to respond poorly to thermotherapy.

PMID- 15947965
TI  - Diurnal variation in CREB phosphorylation and PER1 protein levels in lactotroph
      cells of melatonin-proficient C3H and melatonin-deficient C57BL mice:
      similarities and differences.
AB  - The pineal hormone melatonin plays an important role in the maintenance of
      rhythmic functions of the hypophyseal pars tuberalis, which controls the
      lactotroph cells of the pars distalis. To analyze the effects of melatonin
      deficiency on the activity state of these cells, we have investigated the levels
      of Ser133-phosphorylated (p)CREB and PER1 protein in immunocytochemically
      identified lactotroph cells of melatonin-proficient C3H and melatonin-deficient
      C57BL mice at four different time points of a 12/12 LD cycle. At night, the
      percentage of lactotroph cells showing a positive nuclear pCREB and PER1
      immunoreaction is significantly smaller in C57BL than in C3H mice. In both mouse
      strains, the percentage of pCREB-immunoreactive cells is minimal in the early
      morning and gradually increases to reach a maximum in the late night. PER1 levels
      show a parallel temporal variation in C3H, but in C57BL, they are drastically
      reduced in the early afternoon. The observation that, during darkness, the
      percentage of lactotroph cells with nuclear pCREB immunoreaction is significantly
      higher in C3H than in C57BL mice suggests the existence of a distinct cell
      population that is under the control of melatonin-dependent intrapituitary
      signaling. Interestingly, the percentage of pCREB- and PER1-immunoreactive
      lactotroph cells reaches minimal and maximal values at the same time points. This
      suggests that the correlation between CREB phosphorylation and PER1 induction
      differs between these cells and other neuroendocrine centers, e.g., the pineal
      organ and suprachiasmatic nucleus, displaying a temporal gap between CREB
      phosphorylation and PER1 induction.

PMID- 15947966
TI  - FMRFamide-like immunocytochemistry in the brain and subesophageal ganglion of
      Triatoma infestans (Insecta: Heteroptera). Coexpression with beta-pigment
      dispersing hormone and small cardioactive peptide B.
AB  - The distribution of FMRFamide (FMRFa)-like immunoreactivity (LI) was studied in
      the brain and subesophageal ganglion of Triatoma infestans, the insect vector of
      Chagas' disease. The neuropeptide displayed a widespread distribution with
      immunostained somata in the optic lobe, in the anterior, lateral, and posterior
      soma rinds of the protocerebrum, and around the antennal sensory and
      mechanosensory and motor neuropils of the deutocerebrum. FMRFa-immunoreactive
      profiles of the subesophageal ganglion were seen in the mandibular, maxillary,
      and labial neuromeres. Immunostained neurites were detected in the medulla and
      lobula of the optic lobe, the lateral protocerebral neuropil, the median bundle,
      the calyces and the stalk of the mushroom bodies, and the central body. In the
      deutocerebrum, the sensory glomeruli showed a higher density of immunoreactive
      processes than the mechanosensory and motor neuropil, whereas the neuropils of
      each neuromere of the subesophageal ganglion displayed a moderate density of
      immunoreactive neurites. Colocalization of FMRFa-LI and crustacean pigment
      dispersing hormone-LI was found in perikarya of the proximal optic lobe, the
      lobula, the sensory deutocerebrum, and the labial neuromere of the subesophageal
      ganglion. The distribution pattern of small cardioactive peptide B (SCP(B))-LI
      was also widespread, with immunolabeled somata surrounding every neuropil region
      of the brain and subesophageal ganglion, except for the optic lobe. FMRFa- and
      SCP(B)-LIs showed extensive colocalization in the brain of this triatomine
      species. The presence of immunolabeled perikarya displaying either FMRFa- or
      SCP(B)-LI confirmed that each antisera identified different peptide molecules.
      The distribution of FMRFa immunostaining in T. infestans raises the possibility
      that FMRFa plays a role in the regulation of circadian rhythmicity. The finding
      of immunolabeling in neurosecretory somata of the protocerebrum suggests that
      this neuropeptide may also act as a neurohormone.

PMID- 15947967
TI  - F-actin, beta-tubulin, aldolase, and fructose-1,6-bisphosphatase in heteropteran
      ovarioles--I. Immunocytochemical investigations of whole-mounted ovarioles.
AB  - The distribution of F-actin, beta-tubulin, aldolase, and fructose-1,6
      bisphosphatase (FBPase) in ovarioles of four heteropteran species (Ilyocoris
      cimicoides, Coreus marginatus, Lygus pratensis, and Notostira elongata) was
      investigated biochemically and immunocytochemically. Aldolase was found to be
      uniformly distributed in the cytoplasm of trophocytes and follicular cells, with
      the highest concentration in prefollicular cells. Its concentration in follicular
      cells increased during differentiation and reached a peak in ovarian follicles at
      the stage of late choriogenesis. FBPase was observed in the cytoplasm (weak
      reaction) and on cell borders (strong reaction) of both germ line and somatic
      cells. No FBPase or aldolase signal was observed on the F-actin trophic core mesh
      or on stress fibers.

PMID- 15947968
TI  - Formation of siliceous spicules in the marine demosponge Suberites domuncula.
AB  - The siliceous skeleton of demosponges is constructed of spicules. We have studied
      the formation of spicules in primmorphs from Suberites domuncula. Scanning
      electron microscopy and transmission electron-microscopical (TEM) analyses have
      revealed, in the center of the spicules, an axial canal that is 0.3-1.6 microm
      wide and filled with an axial filament. This filament is composed of the enzyme
      silicatein, which synthesizes the spicules. TEM analysis has shown that spicule
      formation starts intracellularly and ends extracellularly in the mesohyl. At the
      initial stage, the axial canal is composed only of silicatein, whereas membranous
      structures and fibrils (10-15 nm in width) can later also be identified,
      suggesting that intracellular components protrude into the axial canal.
      Antibodies against silicatein have been applied for Western blotting;
      intracellularly, silicatein is processed to the mature form (24 kDa), whereas the
      pro-enzyme with the propeptide (33 kDa) is detected extracellularly. Silicatein
      undergoes phosphorylation at five sites. Immunohistological analysis has shown
      that silicatein exists in the axial canal (axial filament) and on the surface of
      the spicules, suggesting that they grow by apposition. Finally, we have
      demonstrated that the enzymic reaction of silicatein is inhibited by anti
      silicatein antibodies. These data provide, for the first time, a comprehensive
      outline of spicule formation.

PMID- 15947969
TI  - Thyroid hormone receptor-beta-selective agonist GC-24 spares skeletal muscle type
      I to II fiber shift.
AB  - Triiodothyronine (T3) is known to play a key role in the function of several
      tissues/organs via the thyroid hormone receptor isoforms alpha (TRalpha) and beta
      (TRbeta). We have investigated the effects of GC-24, a novel synthetic TRbeta
      selective compound, on skeletal muscle fiber-type determination, cross-sectional
      area, and gene expression in rat skeletal muscles. For fiber typing, cross
      sections of soleus and extensor digitorum longus (EDL) muscles were stained for
      myosin ATPase activity at various pHs. Serum T3, T4, and cholesterol levels were
      also determined. Analysis of highly T3-responsive genes, viz., myosin heavy chain
      IIa (MHCIIa) and sarcoendoplasmic reticulum adenosine triphosphatase (SERCA1),
      was performed by quantitative real-time polymerase chain reaction. Equimolar
      doses of T3 and GC-24 had a similar cholesterol-lowering effect. T3, but not GC
      24, decreased fiber type I and increased fiber type II abundance in soleus and
      EDL muscles. Conversely, in EDL, both T3 and GC-24 decreased the mean cross
      sectional area of type I fibers. MHCIIa gene expression was reduced
      (approximately 50%) by T3 and unchanged by GC-24. SERCA1 gene expression was
      strongly induced by T3 (approximately 20-fold) and mildly induced by GC-24
      (approximately two-fold). These results show that GC-24 does not significantly
      alter the composition of skeletal muscle fiber type and further strengthens the
      putative use of GC compounds as therapeutic agents.

PMID- 15947970
TI  - Photoreceptor projection and termination pattern in the lamina of gonodactyloid
      stomatopods (mantis shrimp).
AB  - The apposition compound eyes of gonodactyloid stomatopods are divided into a
      ventral and a dorsal hemisphere by six equatorial rows of enlarged ommatidia, the
      mid-band (MB). Whereas the hemispheres are specialized for spatial vision, the MB
      consists of four dorsal rows of ommatidia specialized for colour vision and two
      ventral rows specialized for polarization vision. The eight retinula cell axons
      (RCAs) from each ommatidium project retinotopically onto one corresponding lamina
      cartridge, so that the three retinal data streams (spatial, colour and
      polarization) remain anatomically separated. This study investigates whether the
      retinal specializations are reflected in differences in the RCA arrangement
      within the corresponding lamina cartridges. We have found that, in all three eye
      regions, the seven short visual fibres (svfs) formed by retinula cells 1-7 (R1
      R7) terminate at two distinct lamina levels, geometrically separating the
      terminals of photoreceptors sensitive to either orthogonal e-vector directions or
      different wavelengths of light. This arrangement is required for the
      establishment of spectral and polarization opponency mechanisms. The long visual
      fibres (lvfs) of the eighth retinula cells (R8) pass through the lamina and
      project retinotopically to the distal medulla externa. Differences between the
      three eye regions exist in the packing of svf terminals and in the branching
      patterns of the lvfs within the lamina. We hypothesize that the R8 cells of MB
      rows 1-4 are incorporated into the colour vision system formed by R1-R7, whereas
      the R8 cells of MB rows 5 and 6 form a separate neural channel from R1 to R7 for
      polarization processing.

PMID- 15947971
TI  - 5-HT1A receptor expression in pyramidal neurons of cortical and limbic brain
      regions.
AB  - We studied expression of the 5-HT(1A) receptor in cortical and limbic areas of
      the brain of the tree shrew. In situ hybridization with a receptor-specific probe
      and immunocytochemistry with various antibodies was used to identify distinct
      neurons expressing the receptor. In vitro receptor autoradiography with (3)H-8-OH
      DPAT ((3)H-8-hydroxy-2-[di-n-propylamino]tetralin) was performed to visualize
      receptor-binding sites. In the prefrontal, insular, and occipital cortex, 5
      HT(1A) receptor mRNA was expressed in pyramidal neurons of layer 2, whereas (3)H
      8-OH-DPAT labeled layers 1 and 2 generating a columnar-like pattern in the
      prefrontal and occipital cortex. In the striate and ventral occipital cortex,
      receptor mRNA was present within layers 5 and 6 in pyramidal neurons and Meynert
      cells. Pyramid-like neurons in the claustrum and anterior olfactory nucleus also
      expressed the receptor. Principal neurons in hippocampal region CA1 expressed 5
      HT(1A) receptor mRNA, and (3)H-8-OH-DPAT labeled both the stratum oriens and
      stratum radiatum. CA3 pyramidal neurons displayed low 5-HT(1A) receptor
      expression, whereas granule neurons in the dentate gyrus revealed moderate
      expression of this receptor. In the amygdala, large pyramid-like neurons in the
      basal magnocellular nucleus strongly expressed the receptor. Immunocytochemistry
      with antibodies against parvalbumin, calbindin, and gamma aminobutyric acid
      (GABA) provided no evidence for 5-HT(1A) receptor expression in GABAergic neurons
      in cortical and limbic brain areas. Our data agree with previous findings showing
      that the 5-HT(1A) receptor mediates the modulation of glutamatergic neurons.
      Expression in the limbic and cortical areas suggested an involvement of 5-HT(1A)
      receptors in emotional and cognitive processes.

PMID- 15947972
TI  - Endometrial cancer.
AB  - Endometrial cancer is the most common gynaecological malignancy in the developed
      world. The majority of cases can be divided into two broad categories based on
      clinico-pathological and molecular characteristics; Type I oestrogen-dependent
      with endometrioid morphology and Type II non-oestrogen-dependent with serous
      papillary or clear cell morphology. As has been described for other malignancies,
      such as colorectal carcinoma, the transition from normal endometrium to carcinoma
      is thought to involve a stepwise accumulation of alterations in cellular
      regulatory pathways leading to dysfunctional cell growth. This article reviews
      the current knowledge of the molecular changes commonly associated with
      endometrial cancer and presents possible progression models.

PMID- 15947973
TI  - GnRH systems of Cichlasoma dimerus (Perciformes, Cichlidae) revisited: a
      localization study with antibodies and riboprobes to GnRH-associated peptides.
AB  - The distribution of cells that express three prepro-gonadotropin-releasing
      hormones (GnRH), corresponding to salmon GnRH, sea bream GnRH (sbGnRH), and
      chicken II GnRH, was studied in the brain and pituitary of the South American
      cichlid fish, Cichlasoma dimerus. Although the ontogeny and distribution of GnRH
      neuronal systems have previously been examined immunohistochemically with
      antibodies and antisera against the various GnRH decapeptides, we have used
      antisera against various perciform GnRH-associated peptides (GAPs) and riboprobes
      to various perciform GnRH+GAPs. The results demonstrate that: (1) the GnRH
      neuronal populations in the forebrain (salmon and sea bream GAPs; sGAP and sbGAP,
      respectively) show an overlapping pattern along the olfactory bulbs, nucleus
      olfacto-retinalis, ventral telencephalon, and preoptic area; (2) projections with
      sGAP are mainly located in the forebrain and contribute to the pituitary
      innervation, with projections containing chicken GAP II being mainly distributed
      along the mid and hindbrain and not contributing to pituitary innervation,
      whereas sbGAP projections are restricted to the ventral forebrain, being the most
      important molecular form in relation to pituitary innervation; (3) sbGnRH (GnRH
      I) neurons have an olfactory origin; (4) GAP antibodies and GAP riboprobes are
      valuable tools for the study of various GnRH systems, by avoiding the cross
      reactivity problems that occur when using GnRH antibodies and GnRH riboprobes
      alone.

PMID- 15947974
TI  - [Inflammatory diseases of the gall bladder and biliary system. II. Acute and
      chronic inflammation of the biliary system--primary biliary cirrhosis].
AB  - Inflammatory diseases of the biliary tract are divided into acute and chronic
      forms. Acute inflammation of the biliary tree is ascending cholangitis. Among
      chronic forms of the disease, primary sclerosing cholangitis, parasitic infection
      of the biliary tract, AIDS cholangiopathy, and chemotherapy cholangitis are
      recognised. Primary biliary cirrhosis and chronic inflammation of the papilla are
      also categorized within this group of inflammatory diseases of the biliary tree.
      Cross-sectional imaging modalities, such as sonography, computed tomography and
      magnetic resonance imaging, offer numerous possibilities for depicting the
      biliary system with high diagnostic accuracy. In contrast to the gallbladder,
      invasive imaging modalities of the biliary tree are also used for diagnostic
      purposes in addition to their therapeutic aspects.

PMID- 15947975
TI  - A simulation study on the Ca2+-independent but voltage-dependent exocytosis and
      endocytosis in dorsal root ganglion neurons.
AB  - In patch-clamped somata of dorsal root ganglion (DRG) neurons, two types of
      secretion have been proposed: Ca(2+)-dependent secretion and Ca(2+)-independent
      but voltage-dependent secretion (CIVDS). The Ca(2+)-induced and the
      depolarization-induced membrane capacitance (C(m)) increases contribute 80 and
      20% to the total C(m) increase, respectively (Zhang and Zhou in Nat Neurosci
      5:425, 2002). In order to explore the mechanism of the voltage-dependent C(m)
      change (DeltaC(m)), we constructed a model with sequential states. The simulation
      with this model closely approximates all the experimental data. The model
      predicts that the majority of fusion events (approximately 80%) are so-called
      "kiss-and-run" events, which account for the fast recovery or the rapid retrieval
      feature of the signals. The remaining 20% are attributed to full fusion events,
      which account for a slow retrieval feature. On the basis of the model, one
      mechanism of the activity-dependent endocytosis has revealed a differential
      distribution of vesicles between the kiss-and-run and full fusion states at
      different stimulation frequencies. The quantitative model presented in this study
      may help us to understand the mechanism of the CIVDS and the tightly coupled
      endocytosis found in mammalian DRG neurons.

PMID- 15947976
TI  - Radiographic evaluation and unusual bone formations in different genetic patterns
      in synpolydactyly.
AB  - OBJECTIVE: To compare the radiological findings of heterozygous and homozygous
      subjects with synpolydactyly (SPD) and to discuss their unusual bone formations.
      DESIGN AND PATIENTS: Families with hand and foot SPD were examined. Genetic
      analysis was performed with blood samples and the pedigree was constructed. The
      affected individuals, especially those with distinctive phenotypic features, were
      invited to our orthopaedics clinic for further diagnostic studies. All
      participants underwent detailed clinical and X-ray examinations. RESULTS: Of the
      invited patients, 16 (five female and 11 male; age range 4-37 years, mean age
      10.75 years) were included in our study, and hand and foot radiographs were
      obtained. All subjects had bilateral hand radiographs (32 hands), and 14 had
      bilateral foot radiographs (28 feet). Genetic analysis revealed 12 heterozygote
      (75%) and four (25%) homozygote phenotypes. Among patients enrolled into the
      study nine (three homozygotes, six heterozygotes) had SPD of both hands and feet
      bilaterally (tetrasynpolydactyly). Six unusual bone formations were observed in
      the hands and feet: delta phalanx, delta metacarpal/metatarsal, kissing delta
      phalanx, true double epiphysis, pseudoepiphysis and cone-shaped epiphysis. There
      were major differences in radiological and clinical manifestations of homozygote
      and heterozygote phenotypes. The homozygous SPD presented with very distinctive
      unusual bone formations. CONCLUSION: The existence and variety of unusual bones
      may indicate the severity of penetrance and expressivity of SPD.

PMID- 15947977
TI  - Kikuchi-Fujimoto disease: a case report.
AB  - Kikuchi-Fujimoto disease is a rare benign cervical lymphadenopathy, which often
      affects young adult women. Its etiology and pathogenesis are unknown. We present
      the case of Kikuchi-Fujimoto disease in the Polish population and analyse the
      difficulties in differentiating this disease from the systemic lupus
      erythematosus.

PMID- 15947978
TI  - Can renal fibrosis be reversed?
AB  - New therapeutic approaches are needed to address the current epidemic of chronic
      kidney disease. Beyond delaying the inevitable onset of end-stage kidney disease
      the ultimate dream of clinical therapy is disease regression. Degradation of the
      interstitial matrix proteins is potentially feasible, especially before the
      interstitial "scar" becomes highly organized. Currently the specific matrix
      degrading proteases that perform this function in vivo have not been clearly
      identified although several candidates have been suggested. Reversing renal
      fibrosis will also mandate removal of interstitial myofibroblasts that are the
      major source of the fibrosis-associated interstitial matrix proteins. However,
      the greater therapeutic challenge pertains to the current inability to regenerate
      intact functional nephrons in a site where they have been destroyed. In chronic
      tubulointerstitial damage that typifies all progressive kidney diseases, it is
      not interstitial matrix accumulation per se that leads to renal functional
      decline but rather its destructive effects on neighboring cells. In particular,
      loss of peritubular capillaries and tubules are the morphological features that
      underlie declining renal function. Recent advances in several basic scientific
      fields of investigation such as matrix biology, developmental biology,
      angiogenesis, and stem cell biology have identified new candidate therapeutic
      targets. A powerful new molecular tool-box is at our disposal that can be used to
      begin to translate recent discoveries into the clinical research arena with the
      goal of reversing renal fibrosis in a functionally meaningful way.

PMID- 15947979
TI  - Acute renal failure after overdose of colloidal bismuth subcitrate.
AB  - Bismuth salts are widely used to treat peptic ulcers. Acute toxicity with
      colloidal bismuth subcitrate overdose causes nephrotoxicity. There have been
      numerous reports of encephalopathy after long-term consumption of bismuth salts,
      but only a few cases of nephrotoxicity (adult and pediatric) have been documented
      to date. This report presents a case of acute renal failure due to colloidal
      bismuth subcitrate overdose in adolescent. A 16-year-old girl presented with
      complaints of nausea, vomiting, and facial paresthesia. Ten days earlier she had
      tried to commit suicide by taking 60 tablets of De-nol (colloidal bismuth
      subcitrate 18 g). The physical examination findings on admission indicated
      minimal fluid overload but no signs of encephalopathy. Laboratory tests on
      admission showed blood urea nitrogen 102 mg/dl, serum creatinine 19.9 mg/dl, and
      serum bismuth level 495 microg/l. The patient was started on appropriate fluid
      therapy and penicillamine as a chelating agent and then began hemodialysis on
      alternate days. The patient's renal function gradually returned to normal over 9
      weeks and by 64 days after the overdose her serum bismuth level had fallen to
      almost half the level detected 2 days after admission. The patient made a
      complete recovery. The case demonstrates that acute renal failure can develop as
      a manifestation of acute toxicity from colloidal bismuth ingestion, and that the
      prognosis may be favorable if the patient receives appropriate supportive
      treatment and dialysis.

PMID- 15947980
TI  - Acute renal failure in Nigerian children: Port Harcourt experience.
AB  - Acute renal failure (ARF) is a significant cause of morbidity and mortality in
      children. It may be pre-renal, intrinsic, or post-renal (obstructive) in
      aetiology. ARF was investigated in children in the south-southern part of Nigeria
      to determine the prevalence, aetiology, management and outcome of ARF. A
      retrospective review of data from all children from birth to 16 years of age
      admitted into the Department of Paediatrics, University of Port Harcourt Teaching
      Hospital (UPTH), with the diagnosis of ARF over an 18 year period (January 1985
      to December 2003) was performed. Information was obtained about the age, sex,
      clinical features, blood pressure, laboratory and radiological investigations,
      aetiology, and treatment received including dialysis. Information on the outcome,
      factors influencing outcome, and possible causes of death were reviewed. There
      were 211 patients, 138 (65.4%) males and 73 (34.6%) females (M:F, 1.9:1), with a
      hospital prevalence of 11.7 cases/year. The patients were aged 5 days to 16 years
      (mean 5.6+/-4.7 years). Oliguria was the most common clinical presentation in 184
      (87.2%) patients. Hypertension was seen in only 39 (18.5%) patients. The causes
      were age-related. The neonates had ARF from severe birth asphyxia 27 (35.5%),
      septicaemia 17 (22.4%), with tetanus 4 (5.3%) and congenital malformations 11
      (14.5%). Sixty-one (28.9%) and 29 (13.7%) patients had ARF from gastroenteritis
      and malaria respectively. The patients with leukaemia were all more than 10 years
      old and had acute lymphoblastic leukaemia. Two patients (1.9%) had Burkitts
      lymphoma involving the abdomen and 3 patients had HIVAN. 112 (53%) patients had
      anaemia with a mean haematocrit of 20.25+/-6.9%. Dialysis was indicated in 108
      patients, but only 24 patients (22.2%) had peritoneal dialysis (PD), because of
      financial constraints and lack of dialysis equipment. Mortality rate was 40.5%.
      The causes of death were uraemia 60 (70.6%), overwhelming infection 5 (5.9%), and
      recurrent anaemia 20 (23.5%). Hypertension (X2 15.7, P<0.001) and lack of
      dialysis (X2 7.96, P<0.01) significantly affected outcome. Other factors
      associated with demise were delayed presentation (58.8%), use of herbal treatment
      (35%), and unaffordability of treatment (40%). ARF is a significant cause of
      mortality in Nigerian children. The patients are not adequately managed because
      of poverty and lack of facilities for dialysis. The causes of ARF in our
      environment are preventable, and should be expected.

PMID- 15947982
TI  - White-coat and masked hypertension in children: association with target-organ
      damage.
AB  - White-coat hypertension (WCH) and masked hypertension have been associated with
      increased cardiovascular risk in adults. In the current study, we investigated:
      (a) the prevalence of WCH and masked hypertension in pediatric patients and (b)
      the association of these conditions with target organ damage. A total of 85
      children underwent office blood pressure measurements, 24-h ambulatory blood
      pressure monitoring, echocardiography and ultrasonography of the carotid
      arteries. Subjects with both office and ambulatory normotension or hypertension
      were characterized as confirmed normotensives or hypertensives, respectively; WCH
      was defined as office hypertension with ambulatory normotension and masked
      hypertension as office normotension and ambulatory hypertension. WCH was found in
      12.9% and masked hypertension in 9.4% of the subjects. WCH was significantly more
      prevalent in obese subjects, while masked hypertension was only present in non
      obese ones. Confirmed and masked hypertensives had significantly higher left
      ventricular mass index than confirmed normotensives (34.0+/-5.8 g/m(2.7), 31.9+/
      2.9 g/m(2.7) and 25.3+/-5.6 g/m(2.7), respectively, P<0.05). White-coat
      hypertensives tended to have higher left ventricular mass index than confirmed
      normotensives, but the difference was not statistically significant (27.8+/-5.1
      g/m(2.7) versus 25.3+/-5.6 g/m(2.7)). No significant differences were found in
      the intima-media thickness of the carotid arteries between confirmed
      normotensives, white-coat hypertensives, masked hypertensives and confirmed
      hypertensives. WCH and masked hypertension are common conditions in children.
      Confirmed and masked hypertension in pediatric patients are accompanied by
      increased left ventricular mass index.

PMID- 15947981
TI  - Prophylactic theophylline to prevent renal dysfunction in newborns exposed to
      perinatal asphyxia--a study in a developing country.
AB  - Renal damage frequently complicates perinatal asphyxia. Renal vasoconstriction
      due to adenosine metabolite leads to a fall in glomerular filtration rate (GFR)
      and filtration fraction. This might be inhibited by the nonspecific adenosine
      receptor antagonist, theophylline. This study was designed to determine whether
      theophylline could prevent and/or ameliorate renal dysfunction in term neonates
      with perinatal asphyxia. We randomized 40 severely asphyxiated term infants to
      receive intravenously a single dose of either theophylline (5 mg/kg; study group:
      n=20) or placebo (control group: n=20) during the first hour of life. Fluid
      intake, urine output, serum creatinine, creatinine clearance, GFR, urinary beta2
      microglobulin (beta2 M) and sodium excretion were recorded during the first 5
      days of life. The two groups were comparable. No significant difference was
      reported regarding mechanical ventilatory support, respiratory complications and
      seizures. Severe renal dysfunction was significantly higher in the control group.
      Serum creatinine values were less, and creatinine clearance and GFR were
      significantly higher in the theophylline group from the second day onwards. beta2
      M excretion was significantly less in the theophylline group, while sodium
      excretion and hematuria showed no significant difference. Prophylactic
      theophylline treatment, given early after birth, has beneficial effects in
      reducing the renal involvement in asphyxiated full-term infants, with no
      significant changes in central nervous system involvement.

PMID- 15947983
TI  - Successful medical treatment of multiple brain abscesses due to Nocardia
      farcinica in a paediatric renal transplant recipient.
AB  - Brain abscesses caused by Nocardia are rare, but it is very important to detect
      and treat them early because the associated mortality is 3 times higher than that
      associated with other bacterial brain abscesses. This infection is prevalent
      among adults on long-term immunosuppressive therapy; we report the case of a male
      kidney transplant recipient aged 12.7 years who developed early multiple Nocardia
      induced brain abscesses that were successfully treated with linezolid, a novel
      antibiotic therapy.

PMID- 15947984
TI  - Zero balance ultrafiltration (Z-BUF) in blood-primed CRRT circuits achieves
      electrolyte and acid-base homeostasis prior to patient connection.
AB  - Infants requiring CRRT present a unique challenge due to the large circuit volume
      to blood volume ratio. Blood priming is often used, but some patients can become
      unstable during the initiation of CRRT due to electrolyte and acid-base
      imbalance. We postulated that using Z-BUF we could normalize electrolytes and
      improve the acid base status of the prime prior to patient connection. To test
      this we set up a circuit using the Baxter BM-25 CRRT pump, a polysulfone or AN-69
      membrane, and a three-way stopcock. The circuit was primed with a 60/40 mix of
      expired autologous donor pRBCs and 5% albumin. The modalities of CVVH, CVVHD, and
      CVVHDF were compared for relative efficacy. Electrolytes, lactate, pH, cytokines
      (TNF-alpha, IL-1beta, bradykinin, and IL-6) were measured. Plasma hemoglobin
      levels were also measured before and after the Z-BUF procedure. Bradykinin
      production and elimination in AN-69 membrane circuits were assessed. All lab
      values equilibrated by 35 minutes. All CRRT modalities were equally efficacious
      for Z-BUF. Cytokine production or significant hemolysis was not found. In
      addition, no bradykinin accumulation occurred in AN-69 membrane-containing
      circuits. We conclude that Z-BUF is a simple and effective way to normalize
      electrolyte and acid-base status in the CRRT circuit when blood priming is
      required.

PMID- 15947985
TI  - Mating worms and the cystic kidney: Caenorhabditis elegans as a model for renal
      disease.
AB  - Polycystic kidney disease (PKD) is caused by a group of variably inherited human
      disorders that are major causes of end-stage renal disease in both children and
      adults. The genetic culprits responsible for autosomal-dominant PKD (ADPKD), the
      polycystins, have been identified, yet still little is known about the molecular
      mechanisms that result in the disease phenotype. Polycystin homologs have been
      isolated in the model genetic organism Caenorhabditis elegans and, interestingly,
      play a specific role in C. elegans male mating behavior. Despite the recruitment
      of the polycystins for divergent functions in worms and humans it appears that
      the fundamental molecular and genetic interactions of these genes are
      evolutionarily conserved. In addition, studies in the worm have contributed to an
      understanding of the emerging role for cilia in the function of the polycystin
      pathway, expanding a promising frontier in PKD research. C. elegans has also been
      used to identify a gene family which may have significance for understanding the
      formation and maintenance of renal tubules.

PMID- 15947986
TI  - Effect of verocytotoxins (Shiga-like toxins) on human neutrophils in vitro.
AB  - Neutrophil activation occurs in diarrhoea-associated HUS and correlates with
      disease severity, implying a role in pathogenesis. Verocytotoxin (Shiga-like
      toxin) has been shown to stimulate endothelium to release chemokines and express
      leukocyte adhesion molecules that would lead to indirect neutrophil-endothelial
      interaction. A direct action of verocytotoxin (VT) on neutrophils has been
      proposed, although in vitro studies of this are controversial. In this report we
      examine the effect of verocytotoxin-1 (Shiga-like toxin-1) (VT1) and
      verocytotoxin-2 (VT2) on human neutrophils in vitro with regard to priming, the
      release of superoxide and elastase, and chemotaxis. Neutrophils were incubated
      with VT1 or VT2 and superoxide and elastase release was measured over 120 and 45
      minutes respectively. Priming was investigated by pre-treating the neutrophils
      with VT1 or VT2, exposing them to formyl-met-leu-phe (fMLP) or phorbol myristic
      acid (PMA) and measuring superoxide release. Neutrophil chemotaxis towards fMLP
      was assessed with and without pre-incubation with VT1 and VT2. We found that
      neither of the toxins induced superoxide or elastase release. Priming with VT1
      significantly reduced superoxide release when neutrophils were stimulated with
      fMLP or PMA. VT2 priming gave a reduced superoxide release with PMA but not fMLP.
      Heat-inactivation of the toxins gave similar results. Pre-treatment of
      neutrophils with VT1 or VT2 did not affect chemotaxis towards fMLP after a 2-hour
      incubation period. In conclusion, VT1 and VT2 do not activate primed neutrophils
      in vitro. Nor do they affect chemotaxis towards fMLP. They may impair neutrophil
      priming.

PMID- 15947988
TI  - Proteinuria in South Asian children: prevalence and determinants.
AB  - Proteinuria in children is a marker of kidney disease and atherosclerosis, both
      which are known predictors of cardiovascular mortality. Recent evidence suggests
      that migrant South Asian populations living in the West may be at higher risk of
      kidney disease than native Caucasians. However, the determinants of proteinuria
      in South Asian children have not been explored. Previously, we reported ethnic
      variation in the prevalence of proteinuria in the adult population of Pakistan.
      However, it is not known whether ethnic predisposition to proteinuria appears
      during childhood or whether it is acquired later in life as a result of prolonged
      exposure to undiagnosed diabetes and hypertension. Analyses were based on a
      subset of data for 4977 children aged 5 to less than 15 years collected as part
      of the broad National Health Survey of Pakistan, conducted between 1990 and 1994.
      Proteinuria was defined as a dipstick positive for protein on a random urine
      sample. Ethnicity was reported as "mother-tongue", which is specific for each of
      the five major ethnic subgroups of Pakistan: Muhajir, Punjabi, Sindhi, Pashtun,
      and Baluchi. The overall prevalence (95% CI) of proteinuria in the children was
      3.3% (2.7-3.9%). It was 6.2% in Sindhis, 3.6% in Muhajirs, 2.8% in Punjabis, 2.8%
      in Baluchis, and 1.0% in Pashtuns (p<0.001). In multivariable analyses,
      proteinuria was associated with greater height (p=0.007), urban dwelling
      (p=0.03), lower socioeconomic status (p=0.02), and certain ethnicities (p=0.005).
      The ethnic variation in proteinuria in South Asian children mirrors variation
      among ethnic groups in adults. This suggests variations in susceptibility or
      early exposure to causes of chronic kidney disease, rather than long-term
      exposure to undiagnosed diabetes or hypertension. Further studies are needed to
      determine factors in early life that may differentially predispose certain ethnic
      groups to proteinuria.

PMID- 15947989
TI  - Clinicopathologic features, outcome, and therapeutic interventions in four
      children with isolated C3 mesangial proliferative glomerulonephritis.
AB  - Since isolated C3 mesangial proliferative glomerulonephritis in the absence of
      systemic disease (i-C3-GN) is an uncommon chronic glomerular disease, long-term
      prognosis and optimal therapeutic intervention for it are not yet fully defined,
      especially in children. We report clinical features, outcome, and interventions
      in 4 patients, ranging from 6 to 18 years old, with i-C3-GN. Microscopic or
      macroscopic hematuria with or without proteinuria was first noted between 3 and 8
      years. When present, proteinuria ranged from 0.2 to 1.0 g/24 h. Persistent
      hypocomplementemia and circulating immune complexes were found in 1 patient. None
      of the patients had nephrotic syndrome or hypertension. Percutaneous renal biopsy
      specimens showed varying degrees of mesangial proliferative glomerulonephritis; 2
      patients showed mild mesangial proliferation, while others exhibited moderate
      histologic severity. In 1 patient with a mild mesangial increase,
      tubulointerstitial changes were associated. Both patients exhibiting mild
      mesangial changes followed a benign clinical course with normal renal function
      over 10 years of follow-up. Patients with moderately severe mesangial alteration
      manifested slight renal function loss and moderate proteinuria at the time of
      biopsy, but these largely resolved after a six-month course of prednisolone
      combined with cyclophosphamide, warfarin, and an angiotensin-converting enzyme
      inhibitor. Thus, clinical manifestations and the need for aggressive treatment
      appear to vary among pediatric patients with i-C3-GN. Therapy combining
      prednisolone with immunosuppression seemed to reduce proteinuria and improve
      glomerular function in patients with moderately severe mesangial proliferation.

PMID- 15947987
TI  - Oro-dental health in children with chronic renal failure and after renal
      transplantation: a clinical review.
AB  - As a consequence of chronic renal failure (CRF) and its treatment, a number of
      oro-dental changes occur that persist after the end-stage is reached. An early
      effect is enamel hypoplasia due to a defect of enamel development and
      mineralisation. This is usually reparable to a high aesthetic standard using
      dental composite filling material. Children with CRF have significantly less
      dental caries than healthy children due to the inhibitory effect of increased
      salivary urea levels. Grafted patients frequently develop gingival enlargement as
      a result of immunosuppression with cyclosporine A, which is further exacerbated
      by the additional use of antihypertensive calcium-blocking agents. Surgical
      reduction of gingival hyperplasia is effective and is required in approximately
      one third of adolescents. A very high standard of home care should be encouraged
      for all children with CRF in the form of thorough mechanical tooth cleaning and
      plaque inhibition through the use of an antibacterial mouthwash. In transplanted
      children presenting an increased risk of infection, antibiotic prophylaxis may be
      indicated for dental treatment procedures. The drug dosage should be adapted to
      the reduced renal function. Pediatric nephrologists should be aware that dental
      surgeons can make a considerable contribution to the general health and well
      being of children with CRF. Thus, only oro-dental problems that are mainly
      encountered and treated by dental surgeons are reviewed.

PMID- 15947990
TI  - Hematuria and proteinuria in a mass school urine screening test.
AB  - A total of 1,044 school children identified with hematuria and/or proteinuria
      during a mass school urine screening test were referred to pediatric
      nephrologists at 13 hospitals in Korea. These children had isolated hematuria
      (IH) (60.1%), isolated proteinuria (IP) (26.4%: transient, 19.6%; orthostatic,
      4.9%; persistent, 1.9%) or combined hematuria and proteinuria (CHP) (13.5%). The
      patient's history, physical examination, laboratory tests, kidney ultrasound and
      Doppler ultrasonography were obtained. Renal biopsies were performed on 113
      children who showed severe proteinuria, hypertension, abnormal renal function,
      family history of chronic renal disease, systemic diseases or persistent
      hematuria and/or proteinuria for more than 12 months. IgA nephropathy (IgAN),
      thin basement membrane nephropathy (TBMN), membranoproliferative
      glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), other GN,
      Alport syndrome and lupus nephritis were detected. IgAN and TBMN were the most
      common causes in the CHP group and IH group, respectively. Abnormal findings on
      the renal ultrasound with or without Doppler ultrasonography were noted in 147
      cases (suspected nutcracker phenomenon, 65; increased parenchymal echogenicity,
      40; hydronephrosis, 15). This study showed that the use of a mass school urine
      screening program can detect chronic renal disease in its early stage and
      recommends that more attention should be paid to identifying those children with
      CHP and massive proteinuria. A school urine screening program can detect chronic
      renal disease in its early stage. When mass screening is used, the initial
      aggressive diagnostic procedures such as renal biopsy are not needed. In
      addition, a regular follow-up for those children with IH and IP is certainly
      warranted.

PMID- 15947991
TI  - Renal manifestations in Henoch-Schonlein purpura: a 10-year clinical study.
AB  - Henoch-Schonlein purpura (HSP) is an IgA-mediated systemic small vessel
      vasculitis of childhood. It is characterized by the symptoms including
      nonthrombocytopenic purpura, abdominal pain, hematuria/proteinuria, and
      arthargia/arthritis. We conducted a retrospective study of 261 patients diagnosed
      with HSP from December 1991 to December 2001. Of the 261 patients, fifty-three
      (20.3%) developed renal manifestations after onset of the disease. Two patients
      developed nephrotic syndrome. Four patients had group A beta-hemolytic
      streptococcal pharyngitis and subsequent depressed serum C3 concentration typical
      of post streptococcal glomerulonephritis. During the study period, the renal
      survival rate after disease onset was 100%. The prognosis of renal involvement
      was better than reports from other series. In this study we also found factors
      associated with HSP nephritis; these included older age at onset, GI bleeding,
      and central nervous system involvement. The long-term morbidity of HSP is
      predominantly attributed to renal involvement. It is thus recommended that
      patients with HSP nephritis are followed for longer periods of time.

PMID- 15947993
TI  - Cyclosporin A therapy for severe Henoch-Schonlein nephritis with nephrotic
      syndrome.
AB  - To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch
      Schonlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9-13.8
      years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were
      5.5 years (range 2-9 years). All underwent renal biopsy before treatment, and
      follow-up renal biopsy was performed in six of the seven patients. All patients
      improved, with 24-h protein declining from a mean of 9.2 g/m(2)/day (range 1.5-16
      g/m(2)/day) to 0.3 g/m(2)/day (range 0.03-1.2 g/m(2)/day) (p=0.016) and serum
      albumin increasing from a mean of 2.1 g/dl (range 1.5-2.4 g/dl) to 4.6 g/dl
      (range 3.5-5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased
      significantly at the second renal biopsies obtained at a mean interval of 11.7
      months after the first (6.4+/-3.3 vs 3.5+/-1.2, p=0.042, respectively), while the
      chronicity index and the tubulointerstitial scores did not change. On the
      immunofluorescent findings at the second biopsies, the degree of deposits of
      immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six
      patients. Although this case series is without controls, our study suggests that
      CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.

PMID- 15947992
TI  - Hemodialysis in children: general practical guidelines.
AB  - Over the past 20 years children have benefited from major improvements in both
      technology and clinical management of dialysis. Morbidity during dialysis
      sessions has decreased with seizures being exceptional and hypotensive episodes
      rare. Pain and discomfort have been reduced with the use of chronic internal
      jugular venous catheters and anesthetic creams for fistula puncture. Non-invasive
      technologies to assess patient target dry weight and access flow can
      significantly reduce patient morbidity and health care costs. The development of
      urea kinetic modeling enables calculation of the dialysis dose delivery, Kt/V,
      and an indirect assessment of the intake. Nutritional assessment and support are
      of major importance for the growing child. Even if the validity of these "urea
      only" data is questioned, their analysis provides information useful for follow
      up. Newer machines provide more precise control of ultrafiltration by volumetric
      assessment and continuous blood volume monitoring during dialysis sessions.
      Buffered bicarbonate solutions are now standard and more biocompatible synthetic
      membranes and specific small size material dialyzers and tubing have been
      developed for young infants. More recently, the concept of "ultrapure" dialysate,
      i.e. free from microbiological contamination and endotoxins, has developed. This
      will enable the use of hemodiafiltration, especially with the on-line option,
      which has many theoretical advantages and should be considered in the case of
      maximum/optimum dialysis need. Although the optimum dialysis dose requirement for
      children remains uncertain, reports of longer duration and/or daily dialysis show
      they are more effective for phosphate control than conventional hemodialysis and
      should be considered at least for some high-risk patients with cardiovascular
      impairment. In children hemodialysis has to be individualized and viewed as an
      "integrated therapy" considering their long-term exposure to chronic renal
      failure treatment. Dialysis is seen only as a temporary measure for children
      compared with renal transplantation because this enables the best chance of
      rehabilitation in terms of educational and psychosocial functioning. In long term
      chronic dialysis, however, the highest standards should be applied to these
      children to preserve their future "cardiovascular life" which might include more
      dialysis time and on-line hemodiafiltration with synthetic high flux membranes if
      we are able to improve on the rather restricted concept of small-solute urea
      dialysis clearance.

PMID- 15947994
TI  - Neurogenic bladder in an infant due to spinal arachnoid cyst.
AB  - The urinary bladder of patients with occult spinal defects may become
      dysfunctional, exposing the renal parenchyma to irreversible damage. However,
      during infancy clinical signs are often misdiagnosed. The treatment should be
      aimed at protecting kidneys from severe bladder dysfunction. We report a case of
      a female infant with an arachnoid cyst diagnosed at the age of 6 months, who
      suffered from intractable, repeated febrile urinary tract infections (UTI) for
      the previous 3 months. The images obtained by ultrasonography and voiding
      cystoureterography techniques were typical of a neurogenic bladder. The spinal
      cord was examined by magnetic resonance imaging (MRI), which revealed an
      arachnoid cyst that was surgically treated when the child was 8 months old. The
      postoperative results were excellent: spinal cord MRI was normal after 1 year,
      and the child experienced only one UTI episode in the next 2 years. Such an
      etiology of neurogenic bladder has never been reported in a 6-month-old child.

PMID- 15947995
TI  - Fluoroscopic radiation exposure of the kyphoplasty patient.
AB  - Kyphoplasty (KP) is a minimally invasive technique for the percutaneous
      stabilisation of vertebral fractures. As such, this technique is highly dependent
      upon intraoperative fluoroscopic visualisation. In order to assess the range of
      radiation doses that patients are typically subjected to, 60 consecutive
      procedures using simultaneous bilateral fluoroscopy were analysed with respect to
      exposure time (ET). In a subset of 16 of these patients, a theoretical entrance
      skin dose (ESD) and effective dose was additionally calculated from
      intraoperatively measured dose area product. Average fluoroscopy time for single
      level cases reached 2.2 min (range 0.6-4.3) in the lateral plane and 1.6 min
      (range 0.5-3.0) in the anterior-posterior plane. For multiple level cases the
      corresponding ET per level was 1.7 min (range 0.6-2.9) per level in the lateral
      and 1.1 min (range 0.5-2.0) in the anterior-posterior plane. ESD was estimated as
      an average 0.32 Gy (range 0.05-0.86) in the anterior-posterior and 0.68 Gy (range
      0.10-1.43) in the lateral plane. Effective dose (cumulative from both planes)
      averaged 4.28 mSv (range 0.47-10.14). Safety margins for the development of early
      transient erythema are respected within the presented fluoroscopy times. Longer
      ET in the lateral plane may however breach the 2 Gy threshold. Use of large c
      arms and judiciously operating the exposure is recommended. With regard to
      effective dose, a single fluoroscopy guided KP performed for osteoporotic or
      traumatic vertebral fractures is a safe procedure.

PMID- 15947996
TI  - Commentary on the prevention of paralysis after traumatic spinal cord injury in
      humans: the neglected factor--urgent restoration of spinal cord circulation.
AB  - Although advances in the management of spinal injuries during the past 60 years
      have led to greatly increased life expectancy for paralysed patients, most remain
      disabled. Around the world, spinal injury centres have become specialized
      rehabilitation units, where staff accepts the inevitability of persisting
      paralysis. In part, this pessimism has been based on incorrect information about
      the anatomy and function of the circulation of the spinal cord. Since the
      publication of accurate descriptions of the segmental nature of spinal
      vasculature, research and clinical data suggest that reversal or prevention of
      paralysis after spinal injury may be possible in many patients. These improved
      outcomes will depend on the recognition that urgent correction of cord blood
      supply in patients with traumatic spinal injury is critical to the long-term
      results of treatment. The creation of specialist spinal units within trauma
      centres for the urgent treatment of patients following spinal injury will require
      considerable logistical change, but has the potential to lead to a revolution in
      spinal care, driven by the knowledge that spinal cord function can often be
      saved.

PMID- 15947997
TI  - Two missense mutations of EGR2 R359W and GJB1 V136A in a Charcot-Marie-Tooth
      disease family.
AB  - During mutational analysis of Charcot-Marie-Tooth (CMT) causative genes, we
      identified a CMT family with two missense mutations in different genes. A R359W
      mutation in EGR2 was shared by the affected daughter (proband) and her father. In
      addition, she had a V136A mutation in GJB1, which was determined to be a de novo
      mutation. The daughter with two different gene mutations showed more severe
      clinical, electrophysiological and histopathological phenotypes than her father
      who had only the EGR2 mutation. We suggest that these phenotypic differences
      between the proband and her father may have been caused by an altered effect of
      the genetic modifier in EGR2, or by the additive effect of the EGR2 and GJB1
      mutations.

PMID- 15947998
TI  - Severe, atypical form of dyschondrosteosis (report of two cases).
AB  - We report a mother and her son with unique mesomelic dysplasia. The mesomelic
      shortening in the upper extremities presents features of Leri-Weill syndrome
      (dyschondrosteosis) (OMIM 127300), that of the lower extremities is consistent
      with Langer mesomelic dysplasia (OMIM 249700). Molecular studies showed a
      heterozygous short stature homeobox gene ( SHOX)deletion in both patients. A
      second genetic defect in the other SHOX allele was not found. CONCLUSION: Our
      study broadens the phenotypic spectrum associated with short stature homeobox
      gene functional haploinsufficiency.

PMID- 15947999
TI  - Severe aplastic anaemia complicating Sjogren syndrome in a 2-year-old girl.

PMID- 15948000
TI  - Immune-mediated aplastic anaemia.

PMID- 15948002
TI  - Immunogenic HER-2/neu peptides as tumor vaccines.
AB  - During the last decade, a large number of tumor-associated antigens (TAA) have
      been identified, which can be recognized by T cells. This has led to renewed
      interest in the use of active immunization as a modality for the treatment of
      cancer. HER-2/neu is a 185-KDa receptor-like glycoprotein that is overexpressed
      by a variety of tumors including breast, ovarian, lung, prostate and colorectal
      carcinomata. Several immunogenic HER-2/neu peptides recognized by cytotoxic T
      lymphocytes (CTL) or helper T lymphocytes (TH) have been identified thus far.
      Patients with HER-2/neu over-expressing cancers exhibit increased frequencies of
      peripheral blood T cells recognizing immunogenic HER-2/neu peptides. Various
      protocols for generating T cell-mediated immune responses specific for HER-2/neu
      peptides have been examined in pre-clinical models or in clinical trials.
      Vaccination studies in animals utilizing HER-2/neu peptides have been successful
      in eliminating tumor growth. In humans, however, although immunological responses
      have been detected against the peptides used for vaccination, no clinical
      responses have been described. Because HER-2/neu is a self-antigen, functional
      immune responses against it may be limited through tolerance mechanisms.
      Therefore, it would be interesting to determine whether abrogation of tolerance
      to HER-2/neu using appropriate adjuvants and/or peptide analogs may lead to the
      development of immune responses to HER-2/neu epitopes that can be of relevance to
      cancer immunotherapy. Vaccine preparations containing mixtures of HER-2/neu
      peptides and peptide from other tumor-related antigens might also enhance
      efficacy of therapeutic vaccination.

PMID- 15948001
TI  - Prevalence and incidence of antibodies to Borrelia burgdorferi and to tick-borne
      encephalitis virus in agricultural and forestry workers from Tuscany, Italy.
AB  - The ticks Ixodes persulcatus and Ixodes ricinus are the main vectors of both
      Borrelia burgdorferi sensu lato and tick-borne encephalitis (TBE) virus in
      Eurasia. Borrelia burgdorferi is the cause of Lyme borreliosis, and TBE is a
      biphasic meningoencephalitis induced by an arbovirus belonging to the flavivirus
      family. The principal aims of the current investigation were (i) to determine the
      frequency of serological evidence of Borrelia burgdorferi sensu lato and TBE
      infections in healthy agricultural and forestry workers, (ii) to determine the
      incidence of seroconversion for antibodies against Borrelia burgdorferi sensu
      lato and TBE virus in Tuscan workers during a 1-year survey; and (iii) to assess
      the occupational risk for agricultural and forestry activities in a defined area
      (Tuscany, Italy). A total of 412 blood samples were taken from agricultural and
      forestry workers, and information on age, duration of employment, and history of
      tick bites was collected in a questionnaire to establish the risk factors for the
      diseases. Three hundred sixty-five blood donors from the same region served as
      controls. To estimate the rate of seroconversion, 176 of the agricultural and
      forestry workers were tested 1 year later. IgG and IgM antibodies against
      Borrelia burgdorferi sensu lato and TBE virus were detected in serum by an enzyme
      linked immunosorbent assay and confirmed by Western blot analysis for Borrelia
      burgdorferi and by a test for inhibition of hemagglutination for TBE. Antibodies
      against Borrelia burgdorferi were more frequent among the workers than in the
      control group (7.8% vs. 4.9% in the IgG-IgM enzyme-linked immunosorbent assay and
      7.03% vs. 3.56% in the confirmatory test). No seropositivity was observed for TBE
      virus. Eighteen of 176 subjects who underwent a second blood test developed
      specific antibodies against Borrelia burgdorferi within 1 year.

PMID- 15948004
TI  - In vitro plant regeneration from leaves and internode sections of sweet cherry
      cultivars (Prunus avium L.).
AB  - Regeneration of adventitious shoots from leaves and, for the first time, from
      internode sections were compared and optimized for five economically important
      sweet cherry cultivars, i.e. "Schneiders", "Sweetheart", "Starking Hardy Giant",
      "Kordia" and "Regina" (Prunus avium L.). The influence of basal media, carbon
      source, combination and dosage of phytohormones, ethylene inhibitor such as
      silver thiosulfate and a 16 h:8 h light:dark photoperiod versus complete darkness
      were evaluated. Both, DKW/WPM (1:1) and Quoirin/Lepoivre (QL) basal media
      stimulated organogenesis more than QL/WPM (1:1), Chee and Pool (CP), Murashige
      Skoog (MS), Driver and Kuniyuki (DKW) or woody plant (WPM) media did. An
      induction phase in darkness resulted in lower or zero regeneration rates. The
      best regeneration efficiencies were generally obtained with thidiazuron in
      combination with indole-3-butyric-acid. The addition of silver thiosulfate
      resulted in a similar or reduced regeneration efficiency. Significant genotypic
      variability in adventitious bud formation was evident for both explant sources,
      leaf and internode section. Adventitious shoots were obtained from 11% of leaf
      explants and 50% of internode sections indicating that shoot regeneration from
      internodes was significantly more efficient than from leaves.

PMID- 15948005
TI  - Transgenic grasspea (Lathyrus sativus L.): factors influencing agrobacterium
      mediated transformation and regeneration.
AB  - A reproducible procedure was developed for genetic transformation of grasspea
      using epicotyl segment co-cultivation with Agrobacterium. Two disarmed
      Agrobacterium tumefaciens strains, EHA 105 and LBA 4404, both carrying the binary
      plasmid p35SGUSINT with the neomycin phosphotransferase II (nptII) gene and the
      beta-glucuronidase (gus)-intron, were studied as vector systems. The latter was
      found to have a higher transforming ability. Several key factors modifying the
      transformation rate were optimized. The highest transformation rate was achieved
      using hand-pricked explants for infection with an Agrobacterium culture
      corresponding to OD(600) congruent with 0.6 and diluted to a cell density of
      10(9) cells ml(-1) for 10 min, followed by co-cultivation for 4 days in a medium
      maintained at pH 5.6. Putative transformed explants capable of forming shoots
      were selected on regeneration medium containing kanamycin (100 mug ml(-1)). We
      achieved up to 36% transient expression based on the GUS histochemical assay.
      Southern hybridization of genomic DNA of the kanamycin-resistant GUS-expressive
      shoots to a gus-intron probe substantiated the integration of the transgene.
      Transformed shoots were rooted on half-strength MS containing 0.5 mg l(-1) indole
      3-acetic acid, acclimated in vermi-compost and established in the experimental
      field. Germ-line transformation was evident through progeny analysis. Among T(1)
      seedlings of most transgenic plant lines, kanamycin-resistant and -sensitive
      plants segregated in a ratio close to 3:1.

PMID- 15948007
TI  - Perfusion abnormality of the caudate nucleus in patients with paroxysmal
      kinesigenic choreoathetosis.
AB  - PURPOSE: Previous cerebral blood flow and glucose metabolism studies suggest that
      the basal ganglia or thalamus is involved in the pathogenesis of paroxysmal
      kinesigenic choreoathetosis (PKC). However, the underlying cerebral abnormalities
      in idiopathic PKC have not been elucidated. To localise cerebral perfusion
      abnormalities in PKC, we performed interictal brain perfusion 99mTc
      ethylcysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in
      PKC patients and in normal controls. METHODS: Sixteen patients with idiopathic
      PKC and 18 age- and sex-matched normal controls were included. The patients were
      de novo diagnosed as having PKC, or had not taken medication for at least 3
      months; none of them had structural abnormalities on MRI. Patients had a history
      of PKC attacks of a duration not exceeding 5 min and starting either on one side
      or on both sides of the body. These attacks were always induced by a sudden
      initiation of voluntary movement. PKC attacks were recorded in a hospital after
      being induced by neurology staff in 13 of the 16 patients. Interictal brain
      perfusion 99mTc-ECD SPECT was performed in all 16 patients and 18 normal
      controls. Differences between the cerebral perfusion in the PKC group and the
      normal control group were tested by statistical parametric mapping. Student's t
      test was used for inter-group comparisons. RESULTS: Compared with normal
      controls, patients with idiopathic PKC showed interictal hypoperfusion in the
      posterior regions of the bilateral caudate nuclei (false discovery rate-corrected
      P<0.001 with a small volume correction). CONCLUSION: This study showed that
      cerebral perfusion abnormality of bilateral caudate nuclei is present in
      idiopathic PKC.

PMID- 15948008
TI  - Sewage sludge or cattle slurry as pasture fertilisers: comparative cysticercosis
      and trichostrongylosis risk for grazing cattle.
AB  - Sewage sludge and slurry are used as fertilisers on pastures grazed by ruminants.
      The former may be a source of Taenia saginata, which causes cysticercosis in
      cattle and taeniosis in man. The latter is a source of digestive tract
      strongyles, a major helminth infection in cattle. The interest of application on
      pastures of these two biowastes is environmental (optimal recycling of biowastes)
      and agronomic (fertilisation). The parasitic risk and the fertilisation value of
      such applications on pastures were evaluated during one grazing season. Liquid
      sewage sludge did induce higher herbage biomass, which corresponded to higher
      liveweight gains during the first 2 months of grazing, compared to slurry spread
      pastures and calves grazing them. The sludge group of calves did not acquire live
      cysticerci and thus the risk was nil under the conditions of the study (delay of
      6 weeks between application and grazing). The slurry group of calves did become
      lightly infected with digestive-tract strongyles, mostly Ostertagia ostertagi.
      Under the conditions of this experiment, a 6-week delay between application and
      grazing strongly reduced the risk of infection: it renders compatible the
      agronomic use and requirements of public or animal health.

PMID- 15948006
TI  - Stability of alpha-[11C]methyl-L-tryptophan brain trapping in healthy male
      volunteers.
AB  - PURPOSE: The purpose of this study was to assess the reproducibility in healthy
      volunteers of alpha-[11C]methyl-L-tryptophan (alpha[11C]MT) brain trapping
      imaging with positron emission tomography (PET), using volumes of interest (VOIs)
      and voxel-based image analysis. METHODS: Six right-handed healthy male volunteers
      (34.3+/-10.9 years) with a negative family history for psychiatric disorders were
      scanned twice in the resting condition, 22+/-17 days apart. An unbiased
      semiautomatic segmentation of the brain was used to define VOIs. The trapping
      constant K* (ml g(-1) min(-1)) for alpha[11C]MT was calculated for the whole
      brain and seven brain regions using the graphical method for irreversible
      tracers. In addition, parametric maps of K* were obtained from dynamic scans
      using the same method. Comparison of test and retest K* functional images was
      performed using SPM99. Student's paired t statistic was applied for comparisons
      of alpha[11C]MT brain trapping in a priori selected VOIs. RESULTS: alpha[11C]MT
      brain trapping in VOIs showed a mean variability 2.6+/-1.8% (0.3-5%) for absolute
      and 1.5+/-2.1% (1.4-4.1%) for normalized K*. Intraclass correlations between test
      and retest conditions were 0.61+/-0.34 for absolute K* values and 0.73+/-0.20 for
      K* values normalized by global mean. SPM99 analysis using a height threshold of
      p=0.05 (two tailed) and an extent threshold of 100 voxels showed no significant
      differences between scans. CONCLUSION: Rest measurements in healthy male
      volunteers of the trapping constant for alpha[11C]MT, using PET, appeared to be
      stable during an average interval of 3 weeks.

PMID- 15948009
TI  - Molecular identification and characterization of canine Hepatozoon species from
      Brazil.
AB  - Canine Hepatozoon species from Brazil was molecular identified and characterized
      for the first time. From 31 dogs, 7 were positive for blood smear examination and
      21 positive for PCR. Partial sequences of the 18S rRNA gene from eight naturally
      infected dogs were analyzed. Sequences revealed that Brazilian Hepatozoon is
      closely related with the Japanese Hepatozoon, that has 99% nucleotide identity
      with Hepatozoon canis from Israel, and different from Hepatozoon americanum.
      These results indicate that the canine Hepatozoon species from Brazil is H.
      canis.

PMID- 15948010
TI  - Clonorchis sinensis: molecular cloning and localization of myosin regulatory
      light chain.
AB  - One cDNA clone was purified from an adult Clonorchis sinensis cDNA library, and
      its deduced polypeptide sequence was found to be homologous with myosin
      regulatory light chain (MRLC) of invertebrates and vertebrates. Two amino-acid
      residues, Thr and Ser, were conserved at the phosphorylation sites that regulate
      the function of MRLCs. Recombinant C. sinensis MRLC (rCsMRLC) protein was
      produced and purified from Escherichia coli, and mouse anti-CsMRLC immune sera
      recognized a protein of molecular weight 24 kDa from a soluble protein
      preparation of C. sinensis. The CsMRLC protein was immunohistochemically
      localized to the muscle fibers of the subtegumental muscle layer and to the
      muscles of oral and ventral suckers. However, the rCsMRLC protein proved to be
      less useful antigen for the serodiagnosis of human clonorchiasis.

PMID- 15948011
TI  - Trichinella pseudospiralis infection is characterized by more continuous and
      diffuse myopathy than T. spiralis infection.
AB  - A time course study was performed to reveal the sequence of histopathology after
      Trichinella spiralis or T. pseudospiralis infection in mice. A cyst was formed in
      the former case by about 18 days post infection and prominent myopathy was
      restricted within the cyst. In the latter case, however, no typical cyst was
      formed, and myopathy spread diffusely over the infected muscle tissues occupying
      half the area of muscle sections. An electron microscope observation revealed
      that the disintegration of muscle cells was delayed in T. pseudospiralis
      infection than in T. spiralis infection. Quantitative reverse transcription
      polymerase chain reaction (RT-PCR) showed that apoptosis-related genes were
      expressed for a longer term in muscles infected with T. pseudospiralis than in
      those with T. spiralis, although the same spectrum of genes are mobilized.
      Examined apoptosis-related genes included tumor suppressor genes p53, p53; mouse
      double minute 2, MDM2; cyclin-dependent kinase inhibitor p21 (WAF1), p21(waf) ;
      Bcl-2 associated protein X, BAX; apoptotic protease activating factor 1, Apaf-1;
      Caspase 9 and serine/ threonine protein kinase, PKB. Micro-dissection of the
      infected muscle tissue and subsequent RT-PCR confirmed that the expressions of
      these genes are restricted to tissue with myopathy. Thus, the expression of the
      apoptosis-related genes correlated with continuous and diffuse myopathy caused by
      T. pseudospiralis infection.

PMID- 15948012
TI  - The cannabinoid CB1 antagonist AM 251 produces food avoidance and behaviors
      associated with nausea but does not impair feeding efficiency in rats.
AB  - RATIONALE: A growing body of evidence suggests that cannabinoid CB1 receptor
      antagonists have potential therapeutic utility as appetite suppressants. However,
      the specific mechanisms underlying the reduction in food intake produced by these
      drugs are not well understood. OBJECTIVE: Considering the known antiemetic and
      motor-suppressive effects of CB1 agonists, the present studies were conducted to
      determine if the reductions in food intake induced by the CB1 antagonist AM 251
      could result from nausea or impairments in intake-related motor control, rather
      than solely from appetite suppression. METHODS: Three experiments were conducted
      to examine the effects of AM 251 (2.0, 4.0, or 8.0 mg/kg or vehicle) on detailed
      parameters of food intake, on the development of conditioned taste avoidance, and
      on taste reactivity. RESULTS: In the first experiment, acute administration of AM
      251 dose-dependently decreased food intake; nevertheless, feeding rate (grams
      consumed per time spent eating) and food handling were unaffected, which suggests
      that food intake was not reduced because of severe motor impairments. In the
      second experiment, AM 251 dose-dependently reduced intake of a flavor with which
      it had previously been associated, indicating that conditioned taste avoidance
      had developed. Lastly, AM 251 was found to induce conditioned rejection reactions
      in a dose-dependent manner. CONCLUSIONS: The CB1 antagonist AM 251 may reduce
      food intake in part by inducing nausea or malaise, but not because of
      incoordination or motor slowing related to feeding.

PMID- 15948013
TI  - A positron emission tomography (PET) study of cerebral dopamine D2 and serotonine
      5-HT2A receptor occupancy in patients treated with cyamemazine (Tercian).
AB  - RATIONALE: Cyamemazine (Tercian) is an antipsychotic drug with anxiolytic
      properties. Recently, an in vitro study showed that cyamemazine possesses high
      affinity for serotonin 5-HT(2A) receptors, which was fourfold higher than its
      affinity for dopamine D(2) receptors (Hameg et al. 2003). OBJECTIVES: The aim of
      this study is to confirm these previous data in vivo in patients treated with
      clinically relevant doses of Tercian. METHODS: Eight patients received 37.5, 75,
      150 or 300 mg/day of Tercian depending on their symptomatology. Dopamine D(2) and
      serotonin 5-HT(2A) receptor occupancies (RO) were assessed at steady-state plasma
      levels of cyamemazine with positron emission tomography (PET), using
      [(11)C]raclopride and [(11)C]N-methyl-spiperone, respectively. The effective
      plasma level of the drug leading to 50% of receptor occupancy was estimated by
      fitting RO with plasma levels of cyamemazine at the time of the PET scan.
      RESULTS: Cyamemazine induced near saturation of 5-HT(2A) receptors (RO=62.1
      98.2%) in the frontal cortex even at low plasma levels of the drug. On the
      contrary, occupancy of striatal D(2) receptors increased with plasma levels, and
      no saturation was obtained even at high plasma levels (RO=25.2-74.9%). The
      effective plasma level of cyamemazine leading to 50% of D(2) receptor occupancy
      was fourfold higher than that for 5-HT(2A) receptors. Accordingly, individual 5
      HT(2A)/D(2) RO ratios ranged from 1.26 to 2.68. No patients presented relevant
      increased prolactin levels, and only mild extrapyramidal side effects were
      noticed on Simpson and Angus Scale. CONCLUSION: This in vivo binding study
      conducted in patients confirms previous in vitro findings indicating that
      cyamemazine has a higher affinity for serotonin 5-HT(2A) receptors compared to
      dopamine D(2) receptors. In the dose range 37.5-300 mg, levels of dopamine D(2)
      occupancy remained below the level for motor side effects observed with typical
      antipsychotics and is likely to explain the low propensity of the drug to induce
      extrapyramidal side effects.

PMID- 15948014
TI  - Intra-articular methotrexate in the treatment of rheumatoid arthritis and
      psoriatic arthritis: a clinical and sonographic study.
AB  - The aim of our study was to evaluate the effects of intra-articular methotrexate
      (MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
      Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or
      unique arthritic involvement of one knee, were treated with intra-articular
      injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the
      treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation
      measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte
      sedimentation rate (ESR). On the same days, an ultrasonographic examination of
      the involved knee was performed by two independent experienced operators.
      Synovial thickness in the suprapatellar bursa and the presence of joint effusion
      and Baker's cyst were assessed. An increase of the mean value of maximal knee
      flexion angle and a reduction of the mean values of ESR and VAS between T0, T9
      and T17 were demonstrated. Ultrasonographic evaluation showed significant
      reduction of synovial thickness and joint effusion. No differences were detected
      for the presence of Baker's cyst. We may conclude that repeated intra-articular
      injections of MTX resulted in a decrease of local as well as systemic
      inflammatory signs. As far as we know, this is the first study that explores the
      effects of intra-articular MTX in RA and PsA both clinically and by
      ultrasonography.

PMID- 15948016
TI  - Autoprosthesis buttock augmentation during lower body lift.
AB  - With the increasing popularity of bariatric surgery, patients with multiple body
      contour deformities have become more common in plastic surgery practice. Most of
      the deformities involving the abdomen, thighs, and buttocks can be effectively
      corrected with belt lipectomy and lower body lift. A common problem with this
      procedure is postoperative loss of gluteal projection and resulting flattened
      buttock contour, which is directly proportional to the extent of lower body lift
      achieved. The use of local myocutaneous flaps to provide coverage for the
      lumbosacral defects is a common plastic surgery procedure. The authors have used
      these techniques to create an autologous buttock implant for additional
      projection during a lower body lift. A local myocutaneous flap originating within
      the regularly excised supragluteal tissue is rotated caudally to function as an
      autologous buttock implant. This flap has reliable circulation, can be custom
      designed for each patient, requires minimal additional operating time, and allows
      the creation of more than one flap if necessary. This article describes the
      results of this procedure used for 20 consecutive women. There were no major
      complications, and the most common minor complications included delayed wound
      healing and local hardness in the area, suggesting fat necrosis, which resolved
      without intervention in a few months. High patient satisfaction combined with a
      low complication rate suggests that this reliable, versatile technique nicely
      complements the lower body lift procedure.

PMID- 15948017
TI  - An uncommon complication of secondary augmentation mammoplasty: bilaterally
      massive engorgement of breasts after pregnancy attributable to postinfection and
      blockage of mammary ducts.
AB  - Augmentation mammoplasty is one of the most frequently performed aesthetic
      operations. Galactorrhea and galactocele formation after augmentation
      mammoplasty, while the patient is experiencing the hormonal effects, is rarely
      seen. The cause remains unknown. However, postoperative fibrosis and blockage of
      the mammary ducts after augmentation mammoplasty is a probable cause of this
      formation in some patients. In the reported case, the patient described painful
      massive engorgement of both breasts during the last month of pregnancy and
      inability to breast-feed after delivery. In her history, she had undergone breast
      augmentation via the semicircular periareolar transglandular approach. She had
      experienced an infection at an early stage of her postoperative period and had
      needed to have both prostheses removed. A second breast augmentation mammoplasty
      was performed 1 year after the first operation via the same incision. She was
      content with the result of her second augmentation mammoplasty, up until her
      third pregnancy, at which time she reported inability to breast-feed after her
      delivery. At our examination, it was determined that there was massive painful
      breast engorgement, hyperemia, and inflammation of both breasts attributable to a
      bilateral galactocele formation. She refused to take any medication
      (bromocriptine), but approved antibiotic treatment. The patient responded to the
      antibiotics, and the prostheses therefore were left in place without further
      complications.

PMID- 15948018
TI  - Management for postoperative complications of breast augmentation by injected
      polyacrylamide hydrogel.
AB  - Polyacrylamide hydrogel, a new biomaterial, has been used for injected breast
      augmentation in China since 1997. A series of 30 patients with various
      complications after injected polyacrylamide hydrogel visited the author's
      department. Most of these patients had undergone injection of both breasts. The
      average age of the patients was 27.6 years, and the time of consultation for the
      complications was from 3 to 36 months postopertively. Nearly all the patients had
      breast lumps and other common complications including breast pain, disfigurement,
      and infection. Ultrasound examination showed diffuse, irregular, anechoic zones
      of mammary tissue. Pathologic results indicated inflammatory cell infiltration
      and fibrous capsular formation. An open suction technique and partial
      mastectomies via periareolar incisions were performed for the all patients. Most
      of their symptoms were relieved after removal of the polyacrylamide hydrogel.
      Only one patient had undergone immediate breast reconstruction with implants,
      whereas five patients had received breast implants secondarily via an axillary
      incision. The authors conclude that polyacrylamide hydrogel should be prohibited
      for injected breast augmentation before more scientific data are available about
      the long effect of the gel in breast tissue.

PMID- 15948019
TI  - In vivo study to assess the viability and mass effect of fascia injection in
      comparison with block fascia graft.
AB  - Recently, fat injection has gained favor among plastic surgeons for soft tissue
      augmentation. However, fat injections lose 50% of their volume after 1 year. The
      profession is in need of an injectable bulking material that gives a long-lasting
      improvement. Using 30 male rats, this study investigated the stability of the
      size and structure of the injected fascia autograft and compared it with
      surgically transplanted fascia. The fascia graft was harvested from the back of
      the rat, big, and divided into two equal pieces. The first piece was minced into
      a paste and injected subcutaneously on the anterior surface of the right ear. The
      other piece was transplanted subcutaneously on the anterior surface of the left
      ear. The grafts were observed for any sign of resorption over 1 to 6
      months.Grossly, injection and transplantation sites were palpable at the end of
      the observation periods. Microscopic examination showed that injected fascia
      maintains its histomorphologic structure. These findings indicate that the
      injected fascia graft is well tolerated, and the size of the graft remained
      stable. According to this study, fascia injection can result in bulking material
      that gives a long-lasting improvement, and can be a viable alternative to other
      methods.

PMID- 15948020
TI  - Any surgeon practicing aesthetic plastic surgery finds the psychological contact
      with a patient to be of exceptional importance.

PMID- 15948022
TI  - Effect of amniotic fluid on peri-implant capsular formation.
AB  - Although commonly used biomaterials are physically and chemically stable,
      nonimmunogenic, and nontoxic, implanted and blood-contact biomaterials trigger a
      wide variety of unwanted responses, including inflammation, thrombosis,
      infection, and fibrosis. Peri-implant fibrosis is the response most commonly seen
      by plastic surgeons. In this study, the authors hypothesized that as hyaluronic
      acid (HA) reduces scar formation by inhibiting the activity of mononuclear
      phagocytes and lymphocytes, human amniotic fluid (HAF), which contains high
      concentrations of HA, HA-stimulating activator (HASA), and other factors, might
      prevent the formation of fibrous capsules and capsule contracture when applied
      intraluminally. Two 1 x 1-cm silicone blocks were placed dorsally into separate
      surgically created pockets underneath the panniculus carnosus muscle, distant
      from the incisions, in each of the 10 rats in the study. At the time of implant
      insertion, 2 ml of HAF was instilled into the cranially located pockets in group
      1, whereas 2 ml of saline solution was instilled into the caudally located
      pockets in group 2. After 6 months, intracapsular static and dynamic pressure
      measurements were made, and then all the peri-implant capsules were excised and
      fixed in 10% neutral buffered formaldehyde. The thicknesses of the capsules were
      measured in three different areas of each section, and a mean was calculated.
      Capsular firmness, according to the static and dynamic pressure readings, was
      significantly greater in the control group, which had saline solution introduced
      into the pocket, than in the treatment group, which had HAF used in the same
      manner. The mean total thickness of the capsules surrounding the implants was
      876.7 microm in the control group, as comparied with 466.8 microm in the HAF
      treated group. This difference was statistically significant (p < 0.001). Because
      of its ability to reduce capsular thickness and firmness and also because it can
      be stored in a freezer if it is prepared in a cell-free manner, HAF would appear
      to be a useful adjunct in the prevention of capsular contracture formation.

PMID- 15948023
TI  - Postoperative camouflage therapy in facial aesthetic surgery.
AB  - BACKGROUND: This study investigated the effectiveness of makeup camouflage
      procedures for patients who have experienced social problems because undesirable
      ecchymoses and edemas after aesthetic surgery, The impacts of camouflage
      procedures for such patients also were studied. METHODS: For this study, 46
      rhinoplasty patients were divided into two groups: postoperative camouflage
      makeup was used for 23 patients, whereas the other 23 patients were assessed as
      the control group, Additionally, 18 blepharoplasty patients also were divided
      into two similar camouflage and control groups. RESULTS: The State-Trait Anxiety
      Inventory test given to the patients postoperatively indicated that postoperative
      makeup provided positive effects for patients. CONCLUSION: The current clinical
      study investigated the effects of cosmetics on the psychological state of
      patients during the postoperative period and included the application of
      camouflage makeup for postrhinoplasty and postblepharoplasty patients with edemas
      and ecchymoses. Psychologically, the patients felt better.

PMID- 15948024
TI  - Contour of the lower third of the face using an intramusculary injectable
      implant.
AB  - BACKGROUND: The mandible contour plays a major role in the beauty and youthful
      look of the face. Few methods are available to create or recover facial contours.
      The author advocates the use of injectable polymethylmethacrylate microspheres
      suspended in a solution of sodium hyluronate 2%, D-1 propanodiol 10%, and
      apyrogenous solution 2.5 ml, applied by means of a minimally invasive procedure
      into deep anatomic planes. The biomatertal is injected in the muscle using
      microcannulas. METHODS: A review of charts from January of 2001 to December of
      2003 was undertaken to search the clinical outcomes from this therapy. RESULTS:
      This technique for contouring the lower third of the face has been used for 487
      patients along 1,383 different sites. There were no significant complications.
      CONCLUSIONS: Excellent results and a high degree of satisfaction were achieved
      among the patients and the medical staff.

PMID- 15948026
TI  - Multidrug resistance-associated protein 1 functions as an efflux pump of
      xenobiotics in the skin.
AB  - PURPOSE: Recent research has identified gene expression of several types of
      xenobiotic transporters in the skin. The aim of this study was to investigate
      whether multidrug resistance-associated protein 1 (MRP1) functions in the skin.
      METHODS: The distribution of [14C]grepafloxacin in vivo and the transport of 1-[2
      amino-5-(2,7-dichloro-6-hydroxy-3-oxo-9-xanthenyl)phenoxy]-2-(2-amino-5
      methylphenoxy)ethane-N,N,N',N'-tetraacetic acid (fluo 3) were examined in the
      skin of Mrp1 knockout mice [FVB/Mrp1(-/-)] and normal mice [FVB/Mrp1(+/+)].
      RESULTS: The tissue-to-plasma concentration ratio of [14C]grepafloxacin was
      higher in the skin of FVB/Mrp1(-/-) mice than that of FVB/Mrp1(+/+) mice. In skin
      slices of hairless mouse incubated with fluo 3 pentaacetoxymethyl ester, the
      accumulation of fluo 3 was significantly increased in the presence of probenecid
      (2 mM) and carbonyl cyanide p-trifluoromethoxyphenylhydrazone (5 muM) in a time
      dependent manner but did not change in the presence of tetraethylammonium (2 mM).
      In FVB/Mrp1(-/-) mouse skin, the accumulation of fluo 3 increased time
      dependently, while no increase was observed in FVB/Mrp1(+/+) mouse skin.
      CONCLUSIONS: These findings suggest that Mrp1 is involved in the efflux of
      [14C]grepafloxacin and fluo 3 in the skin, possibly acting as part of a barrier
      system against xenobiotic compounds.

PMID- 15948027
TI  - Development of a transgenic mouse model immune tolerant for human interferon
      Beta.
AB  - PURPOSE: Therapeutic proteins may induce antibodies that inhibit their efficacy
      or have other serious biological effects. There is a great need for strategies to
      predict whether a certain formulation will induce an immune response. In
      principle, conventional animals develop an immune response against all human
      proteins no matter how they are formulated, which restricts their use. The aim of
      this study was to develop a mouse model immune tolerant for human interferon beta
      (hIFNbeta). METHODS: A transgenic mouse model immune tolerant for hIFNbeta was
      developed by making C57Bl/6 mice transgenic for the hIFNbeta gene. To evaluate
      the model, both wild-type and transgenic mice were immunized with recombinant
      human interferon beta 1a (rhIFNbeta-1a) and recombinant human interferon beta 1b
      (rhIFNbeta-1b). Serum antibodies against rhIFNbeta were detected by ELISA.
      RESULTS: The genetically modified mice were shown to be immune tolerant for
      mammalian cell-derived rhIFNbeta-1a, which has a relative low immunogenicity in
      patients. However, Escherichia coli-derived rhIFNbeta-1b, known to have a
      relatively high immunogenicity in patients, was shown not only to be immunogenic
      in the wild-type mice but could also break the immune tolerance of the
      genetically modified mice. CONCLUSIONS: This animal model offers the possibility
      to study the many factors influencing the immunogenicity of hIFNbeta and test new
      formulations before going into clinical trials. The model also provides the first
      evidence that the rhIFNbetas differ in the immunological mechanisms responsible
      for the development of antibodies.

PMID- 15948028
TI  - Vascular endothelium-selective gene induction by Tie2 promoter/enhancer in the
      brain and retina of a transgenic rat.
AB  - PURPOSE: To produce a transgenic rat harboring the Tie2 promoter/enhancer linked
      green fluorescence protein (GFP) gene and investigate the blood-brain barrier
      (BBB)- and inner blood-retinal barrier (iBRB)-selective GFP expression in the
      brain and retina. METHODS: Transgenic rats were produced by the microinjection of
      mouse Tie2/GFP gene into fertilized oocytes of Wistar rats. The expression of GFP
      was observed in tissue slices by confocal microscopy. RESULTS: One of the
      obtained transgenic lines showed intense GFP expression in vascular endothelial
      cells throughout the brain. After double immunostaining with glucose transporter
      1, the GFP was found to be localized in the cytoplasmic compartment of brain
      capillary endothelial cells. In contrast, no fluorescence was observed in neural
      cells. In the retina of transgenic rats, intense GFP expression was detected in
      retinal capillary endothelial cells. No fluorescence was detected in other cells.
      In kidney and liver, GFP expression was detected in vascular endothelial cells,
      whereas the expressed region was limited. CONCLUSIONS: Mouse Tie2
      promoter/enhancer has the ability to induce gene expression selectively in
      vascular endothelial cells in the brain and retina of transgenic rats.

PMID- 15948029
TI  - Interactions of stevioside and steviol with renal organic anion transporters in
      S2 cells and mouse renal cortical slices.
AB  - PURPOSE: Our previous studies have shown that both stevioside and steviol
      inhibited transepithelial transport of para-aminohippurate (PAH) in isolated
      rabbit renal proximal tubules by interfering with organic anion transport system.
      The current study examined the direct interactions of stevioside and steviol with
      specific organic anion transporters. METHODS: S2 cells expressing human organic
      anion transporters (hOAT1, hOAT2, hOAT3, and hOAT4) and an intact renal
      epithelium were used to determine the inhibitory effect of stevioside and steviol
      on organic anion transport. RESULTS: Stevioside at 0.5-1 mM showed no interaction
      with any OAT. In contrast, steviol markedly inhibited substrate uptake in all
      S2hOAT cells. Steviol had low IC50 for hOAT1 (11.4 microM) and hOAT3 (36.5
      microM) similar to that of probenecid, whereas IC50 for hOAT2 (1000 microM) and
      hOAT4 (285 microM) was much higher. Results obtained in mouse renal cortical
      slices were very similar; that is, stevioside was without inhibitory effect and
      steviol was a potent inhibitor of PAH and estrone sulfate (ES) transport.
      CONCLUSIONS: Stevioside has no interaction with human or mouse OATs. In contrast,
      steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with
      a potency approximating probenecid, suggesting that the inhibition of OAT
      mediated transport by steviol could alter renal drug clearance.

PMID- 15948030
TI  - Formulating paclitaxel in nanoparticles alters its disposition.
AB  - PURPOSE: Paclitaxel is active and widely used to treat multiple types of solid
      tumors. The commercially available paclitaxel formulation uses Cremophor/ethanol
      (C/E) as the solubilizers. Other formulations including nanoparticles have been
      introduced. This study evaluated the effects of nanoparticle formulation of
      paclitaxel on its tissue distribution. METHODS: We compared the plasma and tissue
      pharmacokinetics of paclitaxel-loaded gelatin nanoparticles and the C/E
      formulation. Mice were given paclitaxel-equivalent doses of 10 mg/kg by
      intravenous injection. RESULTS: The nanoparticle and C/E formulations showed
      significant differences in paclitaxel disposition; the nanoparticles yielded 40%
      smaller area under the blood concentration-time curve and faster blood clearance
      of total paclitaxel concentrations (sum of free, protein-bound, and nanoparticle
      entrapped drug). The two formulations also showed different tissue specificity.
      The rank order of tissue-to-blood concentration ratios was liver > small
      intestine > kidney >> large intestine > spleen = stomach > lung > heart for the
      nanoparticles, and liver > small intestine > large intestine > stomach > lung >
      or = kidney > spleen > heart for the C/E formulation. The nanoparticles also
      showed longer retention and higher accumulation in organs and tissues (average of
      3.2 +/- 2.3-fold), especially in the liver, small intestine, and kidney. The most
      striking difference was an 8-fold greater drug accumulation and sustained
      retention in the kidney. CONCLUSIONS: These data indicate that formulation of
      paclitaxel affects its clearance and distribution into tissues, with preferential
      accumulation of nanoparticles in the liver, spleen, small intestine, and kidney.

PMID- 15948031
TI  - log P estimation of 1,2-dithiole-3-thiones and 1,2-dithiole-3-ones: a comparison
      of experimental and calculative approaches.
AB  - PURPOSE: To estimate experimental log P values of formerly described 5-formyl-
      and 5-acyl-dithiole-3-thiones (DTT) and -dithiole-3-ones (DTO) and to check the
      validity of five log P calculation programs via experimental log P for a database
      of 68 DTT and DTO. METHODS: Experimental log P values were measured by means of
      octanol/water partitioning; for determining solute concentrations in water, RP
      HPLC with spectrophotometric detection was used. For calculating log P, the
      fragmental methods ACD/log P, CLOGP, and KOWWIN, the atom-based approach XLOGP,
      and the whole-molecule approach QLOGP were applied. RESULTS: Quality of
      calculations significantly differs depending on the subset under consideration.
      For database compounds 01-48, comprising alkyl and aryl substitution in 4- and 5
      position, the fragmental methods ACD/log P, CLOGP, and KOWWIN perform
      significantly better than the atom-based approach XLOGP and the whole-molecule
      method QLOGP. For database compounds 49-68, comprising formyl and acyl
      substitution in 4- and 5-position, superiority of the whole-molecule method QLOGP
      over the substructure-based approaches is observed. The strong underestimation of
      log P for compounds 49-68 probably indicates hidden physicochemical phenomena
      resulting from the juxtaposition of the acyl and dithiole moieties. CONCLUSIONS:
      All calculation methods included in this study need a thorough refinement to
      adequately cope with particular solvation behavior suspected to prevail in formyl
      or acyl-DTT and DTO, which represent a chemical class of high pharmacological
      interest.

PMID- 15948032
TI  - Tissue-specific characteristics of in vivo electric gene: transfer by tissue and
      intravenous injection of plasmid DNA.
AB  - PURPOSE: To evaluate the tissue-specific characteristics of electric gene
      transfer after tissue and intravenous injection of naked plasmid DNA (pDNA).
      METHODS: pDNA encoding firefly luciferase was injected directly into the liver,
      kidney, spleen, skin and muscle, or into the tail vein of mice, and electric
      pulses were then applied to one of these organs. The distribution of transgene
      expressing cells was evaluated using pDNA encoding beta-galactosidase. RESULTS:
      Tissue injection of pDNA produced a significant degree of transgene expression in
      any tissue with the greatest amount in the liver, followed by kidney and spleen.
      The expression in these organs decreased quickly with time, and muscle showed the
      greatest expression at 7 days. Electroporation significantly increased the
      expression, and the expression level was comparable among the organs. Intravenous
      injection of pDNA followed by electroporation resulted in a significant
      expression in the liver, spleen, and kidney but not in the skin or muscle.
      CONCLUSIONS: Electric gene transfer to the liver, kidney, and spleen can be an
      effective approach to obtain significant amounts of transgene expression by
      either tissue or intravenous injection of pDNA, whereas it is only effective
      after tissue injection as far as skin- or muscle-targeted gene transfer is
      concerned.

PMID- 15948033
TI  - Pharmacokinetics and modeling of quercetin and metabolites.
AB  - PURPOSE: To determine the pharmacokinetics of quercetin and its
      glucuronide/sulfate conjugates and to develop a pharmacokinetic model to
      simultaneously describe their disposition after intravenous and oral
      administration in rats. METHODS: After oral, intraportal, and intravenous
      administration of quercetin, serial plasma, urine, and fecal concentrations of
      quercetin and its conjugates were determined by an HPLC method. Enterohepatic
      recirculation was evaluated in a linked-rat model as well as after oral
      administration of bile containing quercetin and its metabolites. Based on the
      experimental data, a specific compartmental model was developed and validated to
      describe and predict the plasma concentration-time profiles of quercetin and its
      conjugates after oral and intravenous administration. RESULTS: Only 5.3% of
      unchanged quercetin was bioavailable, although the total quercetin absorbed was
      as high as 59.1%. After oral administration, about 93.3% of quercetin was
      metabolized in the gut, with only 3.1% metabolized in the liver. No significant
      enterohepatic recirculation was observed for both quercetin and its conjugated
      metabolites. The pharmacokinetic model fitted well the observed data of quercetin
      and its conjugates. CONCLUSIONS: Our study clarifies the relative importance of
      the gut, liver, and bile in the metabolism and excretion of quercetin and its
      conjugates. The pharmacokinetic model appears to be suitable for describing the
      absorption and disposition of the quercetin and its conjugates and may be
      applicable to other flavonoids that undergo similar pharmacokinetic pathways.

PMID- 15948034
TI  - St. John's Wort modulates the toxicities and pharmacokinetics of CPT-11
      (irinotecan) in rats.
AB  - CPT-11 is a DNA topoisomerase I inhibitor for the therapy of colorectal cancer,
      whereas St. John's Wort (Hypericum perforatum, SJW) is a widely used herbal anti
      depressant. This study aimed to investigate the effects of co-administered SJW on
      the toxicities and pharmacokinetics of CPT-11 and the underlying mechanisms. The
      body weight loss, gastrointestinal and hematological toxicities induced by CPT
      11, and the pharmacokinetic parameters of CPT-11 were evaluated in rats
      pretreated with SJW or vehicle. Rats treated with CPT-11 alone experienced rapid
      decrease in body weight, whereas co-administration of SJW with CPT-11 resulted in
      lesser body weight loss. The gastrointestinal and hematological toxicities
      following CPT-11 injection were both alleviated in the presence of SJW. The rat
      pharmacokinetics of both CPT-11 and its metabolite SN-38 were significantly
      altered in presence of SJW. In conclusion, co-administered SJW significantly
      ameliorated the toxicities induced by CPT-11. The protective effect of SJW may be
      partially due to pharmacokinetic interaction between CPT-11 and SJW.

PMID- 15948035
TI  - Trastuzumab and liposomal Doxorubicin in the treatment of mcf-7 xenograft tumor
      bearing mice: combination does not affect drug serum levels.
AB  - PURPOSE: We assessed the combination of doxorubicin or liposomal doxorubicin with
      trastuzumab for alterations in peak serum drug levels, as these agents are
      increasingly being paired in the treatment of aggressive breast cancer. We
      hypothesized that trastuzumab would exhibit a slower rate of elimination from the
      serum when in combination with liposomal doxorubicin based on the known effects
      of liposomal doxorubicin on phagocytic cells of the mononuclear phagocyte system
      (MPS), which are responsible in part for the uptake and degradation of
      antibodies. METHODS: Doxorubicin and trastuzumab serum levels were assessed
      following injection of free doxorubicin, liposomal doxorubicin, or trastuzumab
      into female RAG2-M mice bearing subcutaneous MCF-7(HER-2) tumors. The effects of
      combination drug treatment on tumor growth were compared to single-agent
      treatment. RESULTS: Peak serum trastuzumab levels were not altered as a result of
      addition of doxorubicin therapy, nor were doxorubicin levels altered over 24 h as
      a result of coadministration of trastuzumab. Liposomal doxorubicin administration
      did result in serum doxorubicin levels 200- to 1000-fold higher than with
      injection of free doxorubicin. CONCLUSIONS: For the specific combination of
      trastuzumab with doxorubicin, either in free or liposomal form, coadministered in
      mice, there was no impact of one drug on the other in terms of peak serum drug
      levels or efficacy.

PMID- 15948036
TI  - The role of capsule on the performance of a dry powder inhaler using
      computational and experimental analyses.
AB  - PURPOSE: To study the fundamental effects of the spinning capsule on the overall
      performance of a dry powder inhaler (Aerolizer). METHODS: The capsule motion was
      visualized using high-speed photography. Computational fluid dynamics (CFD)
      analysis was performed to determine the flowfield generated in the device with
      and without the presence of different sized capsules at 60 l min(-1). The inhaler
      dispersion performance was measured with mannitol powder using a multistage
      liquid impinger at the same flowrate. RESULTS: The capsule size (3, 4, and 5) was
      found to make no significant difference to the device flowfield, the particle
      device impaction frequency, or the dispersion performance of the inhaler.
      Reducing the capsule size reduced only the capsule retention by 4%. In contrast,
      without the presence of the spinning capsule, turbulence levels were increased by
      65%, FPF(Em) (wt% particles < or =6.8 microm in the aerosol referenced against
      the amount of powder emitted from the device) increased from 59% to 65%, while
      particle-mouthpiece impaction decreased by 2.5 times. When the powder was
      dispersed from within compared to from outside the spinning capsule containing
      four 0.6 mm holes at each end, the FPF(Em) was increased significantly from 59%
      to 76%, and the throat retention was dropped from 14% to 6%. CONCLUSIONS: The
      presence, but not the size, of a capsule has significant effects on the inhaler
      performance. The results suggested that impaction between the particles and the
      spinning capsule does not play a major role in powder dispersion. However, the
      capsule can provide additional strong mechanisms of deagglomeration dependent on
      the size of the capsule hole.

PMID- 15948037
TI  - Enhanced intracellular uptake of sterically stabilized liposomal Doxorubicin in
      vitro resulting in improved antitumor activity in vivo.
AB  - PURPOSE: To investigate the correlation between the in vitro intracellular uptake
      and the in vivo antitumor activity of anticancer drugs delivered by sterically
      stabilized liposomes (SSL). METHODS: Arginine-glycine-aspartic acid (RGD) peptide
      or RGD mimetic (RGDm) was coupled onto the surface of SSL to obtain the cell
      binding carrier to facilitate the intracellular delivery of the encapsulated
      drugs. DOX-loaded SSL (SSL-DOX), DOX-loaded RGD-modified SSL (RGD-SSL-DOX) and
      DOX-loaded RGDm-modified SSL (RGDm-SSL-DOX) were prepared by lipid film
      dispersion followed by remote loading of DOX. The intracellular uptake of DOX
      from the various liposomal formulations was evaluated in vitro with melanoma B16
      cells, and the pharmacokinetics, biodistribution, and antitumor activity were
      compared in C57BL/6 mice carrying melanoma B16 tumors. RESULTS: In vitro
      intracellular uptake of DOX by B16 cells and in vivo antitumor activity in terms
      of tumor growth inhibition and mice survival time prolongation for various
      liposomal DOX were in the following order: RGD-SSL-DOX > RGDm-SSL-DOX > SSL-DOX.
      The mean survival time of the mice treated with RGD-SSL-DOX, RGDm-SSL-DOX, and
      SSL-DOX was 55, 49, and 44 days, respectively. The three liposomal DOX
      formulations produced very close DOX accumulation in tumor, which is
      significantly higher than that of free DOX. RGD- or RGDm-SSL-DOX demonstrated
      prolonged circulation time similar to that of SSL-DOX, whereas they showed
      significantly lower DOX level in blood and remarkably higher uptake by spleen
      than SSL-DOX. CONCLUSIONS: Enhanced intracellular uptake of DOX encapsulated in
      SSL could produce an improved therapeutic effect for the melanoma B16 tumors.
      Enhancing intracellular delivery of the anticancer drugs encapsulated in SSL may
      be a promising strategy to improve their therapeutic efficacy for solid tumors.

PMID- 15948038
TI  - Insulin-like growth factor I-releasing alginate-tricalciumphosphate composites
      for bone regeneration.
AB  - PURPOSE: Development and characterization of an in situ-forming, osteoconductive,
      and growth factor-releasing bone implant. METHODS: Injectable in situ-forming
      scaffolds were prepared from a 2% (m/v) alginate solution, tricalciumphosphate
      (TCP) granules, and poly(lactide-co-glycolide) microspheres (MS), loaded with the
      osteoinductive growth factor insulin-like growth factor I (IGF-I). Scaffolds were
      prepared by mixing the components followed by hydrogel formation through calcium
      carbonate-induced physical cross-linking of the alginate at slightly acidic pH.
      Physical-chemical properties and cell biocompatibility using osteoblast-like
      cells (MG-63 and Saos-2) of these scaffolds were investigated. RESULTS: The
      addition of TCP to the alginate resulted in reduced swelling and gelation time
      and an increase in stiffness. Osteoblast-like cells (MG-63 and Saos-2) did not
      show toxic reactions and adhered circumferentially to the TCP granules surface.
      The addition of the IGF-I MS resulted in an up to sevenfold increased
      proliferation rate of MG-63 cells as compared to scaffold preparations without
      IGF-I MS. The alkaline phosphate (ALP) activity-a parameter for osteblastic
      activity-increased with increasing amounts of TCP in Saos-2 loaded composite
      scaffolds. CONCLUSIONS: A prototype in situ-hardening composite system for
      conformal filling of bone defects supporting osteoblastic activity for further
      clinical testing in relevant fracture models was developed and characterized.

PMID- 15948039
TI  - Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin
      nanoparticles: in vitro and in vivo studies.
AB  - PURPOSE: To develop safe and effective systemically administered nonviral gene
      therapy vectors for solid tumors, DNA-containing poly(ethylene glycol)-modified
      (PEGylated) gelatin nanoparticles were fabricated and evaluated in vitro and in
      vivo. METHODS: Reporter plasmid DNA encoding for beta-galactosidase (pCMV-beta)
      was encapsulated in gelatin and PEGylated gelatin nanoparticles using a water
      ethanol solvent displacement method under controlled pH and temperature. Lewis
      lung carcinoma (LLC) cells in culture were transfected with the pCMV-beta in the
      control and nanoparticle formulations. Periodically, the expression of beta
      galactosidase in the cells was measured quantitatively using an enzymatic assay
      for the conversion of o-nitrophenyl-beta-D: -galactopyranoside (ONPG) to o
      nitrophenol (ONP). Qualitative expression of beta-galactosidase in LLC cells was
      observed by staining with 5-bromo-4-chloro-3-indolyl-beta-D: -galactopyranoside
      (X-gal). Additionally, the plasmid DNA-encapsulated gelatin and PEGylated gelatin
      nanoparticles were administered intravenously (i.v.) and intratumorally (i.t.) to
      LLC-bearing female C57BL/6J mice. At various time points postadministration, the
      animals were sacrificed and transgene expression in the tumor and liver was
      determined quantitatively by the ONPG to ONP enzymatic conversion assay and
      qualitatively by X-gal staining. RESULTS: Almost 100% of the pCMV-beta was
      encapsulated in gelatin and PEGylated gelatin nanoparticles (mean diameter 200
      nm) at 0.5% (w/w) concentration. PEGylated gelatin nanoparticles efficiently
      transfected the LLC cells and the beta-galactosidase expression, as measured by
      the ONPG to ONP enzymatic conversion assay at 420 nm absorbance, increased
      starting from 12 h until 96 h post-transfection. The efficient expression of LLC
      cells was also evident by the X-gal staining method that shows blue color
      formation. The in vivo studies showed significant expression of beta
      galactosidase in the tumor following administration of DNA-containing PEGylated
      gelatin nanoparticles to LLC-bearing mice by both i.v. and i.t. routes. Following
      i.v. administration of pCMV-beta in PEGylated gelatin nanoparticles, for
      instance, the absorbance at 420 nm per gram of tumor increased from 0.60 after 12
      h to 0.85 after 96 h of transfection. After i.t. administration, the absorbance
      values increased from 0.90 after 12 h to almost 1.4 after 96 h. CONCLUSIONS: The
      in vitro and in vivo results of this study clearly show that a long-circulating,
      biocompatible and biodegradable, DNA-encapsulating nanoparticulate system would
      be highly desirable for systemic delivery of genetic constructs to solid tumors.

PMID- 15948040
TI  - Cyclodextrin-mediated drug release from liposomes dispersed within a bioadhesive
      gel.
AB  - PURPOSE: The aim of the present study was to design a new mucosal drug delivery
      system composed of liposomes dispersed within a bioadhesive hydrogel containing
      methyl-beta-cyclodextrin (Me(beta)CD) for controlled drug release. METHODS: A
      hydrophilic model molecule, inulin, was encapsulated within positively charged
      and PEG-ylated liposomes and its release was measured in the presence of
      Me(beta)CD after vesicle dispersion within the bioadhesive Carbopol 974P gel.
      Freeze-fracture electron microscopy (FFEM) was used to follow liposome
      morphological changes when dispersed within the hydrogel. Liposome-Me(beta)CD
      interactions were investigated by turbidity monitoring during continuous addition
      of Me(beta)CD to liposomes and by FFEM. RESULTS: Inulin diffusion within the gel
      was influenced by Carbopol 974P concentration since no gel erosion occurred. When
      dispersed within the gel, positively charged liposomes displayed a higher
      stability than PEG-ylated vesicles. In the presence of Me(beta)CD, higher amounts
      of free inulin were released from liposomes, especially in Carbopol-free system.
      Me(beta)CD appeared to diffuse towards lipid vesicles and permeabilized their
      bilayer allowing inulin leakage. Indeed, freeze-fracture experiments and liposome
      turbidity monitoring have shown that Me(beta)CD behaved as a detergent behavior,
      resulting in lipid vesicle solubilization. CONCLUSION: is able to mediate, within
      a bioadhesive hydrogel, the release of a liposome-encapsulated molecule allowing
      further application of this delivery system for mucosal administration.

PMID- 15948041
TI  - N4,N9-dioleoyl spermine is a novel nonviral lipopolyamine vector for plasmid DNA
      formulation.
AB  - PURPOSE: To study the effect of synthesized N4,N9-dioleoyl spermine on DNA
      condensation and then measure its transfection efficiency in cell culture.
      METHODS: The lipopolyamine was synthesized from the naturally occurring polyamine
      spermine. The ability of this novel compound to condense DNA was studied using
      ethidium bromide fluorescence quenching and light scattering assays. Transfection
      efficiency was studied in primary skin cells (FEK4) and in an immortalized cancer
      cell line (HtTA), and compared with the commercially available transfection
      formulations Lipofectin and Lipofectamine. RESULTS: The synthesized N4,N9
      dioleoyl spermine formula is efficient at condensing calf thymus and circular
      plasmid DNA and effectively transfects both primary skin cells and cancer cell
      lines at low charge ratios of (+/- ammonium/phosphate) 2.5. CONCLUSIONS: N4,N9
      Dioleoyl spermine condenses DNA and achieves high transfection levels in cultured
      cells.

PMID- 15948042
TI  - In vitro/in vivo correlation of transdermal naltrexone prodrugs in hairless
      guinea pigs.
AB  - PURPOSE: The purpose of this investigation was to evaluate the in vitro and in
      vivo percutaneous absorption of the following prodrugs of naltrexone (NTX): 2'
      ethylbutyryl-3-O-ester-NTX (ETBUT-ester), methyl-3-O-carbonate-NTX (ME
      carbonate), ethyl-3-O-carbamate-NTX (ET-carbamate), and N,N-dimethyl-3-O
      carbamate-NTX (DME-carbamate) in hairless guinea pigs. METHODS: In vitro fluxes
      of NTX and its prodrugs through guinea pig skin were determined using a flow
      through diffusion cell system. The pharmacokinetics of NTX prodrugs were
      determined after topical application of transdermal patches in guinea pigs.
      RESULTS: All the prodrugs hydrolyzed to NTX on passing through the skin, and ME
      carbonate provided the highest NTX flux and had the highest apparent permeability
      coefficient (K(p)). ME-carbonate and ET-carbamate underwent the highest extent of
      bioconversion to NTX upon passing through the skin as compared to ETBUT-ester and
      DME-carbamate. The results of the in vivo studies indicated that a significant
      amount of NTX was delivered after the application of transdermal patches of NTX
      prodrugs. A mean steady-state plasma concentration of 7.1 ng/ml was obtained
      after the application of transdermal patches of ME-carbonate. A good correlation
      was obtained between the in vitro and in vivo results. CONCLUSIONS: The results
      of the in vivo studies indicated that the ME-carbonate prodrug of NTX was the
      most promising drug candidate for transdermal delivery.

PMID- 15948044
TI  - Solid-state fluorescence studies of some polymorphs of diflunisal*.
AB  - PURPOSE: The solid-state luminescence spectroscopy of organic molecules is
      strongly affected by the effects of excited state energy transfer, with the
      fluorescence of solids often differing significantly from the fluorescence of the
      molecule dissolved in a solution phase. Because the magnitude of these solid
      state effects is determined by the crystallography of the system, solid-state
      fluorescence studies can be used to gain insight into the polymorphism of the
      system. To this end, the spectroscopic properties of four polymorphs of
      diflunisal have been obtained, and compared to the properties of the molecule in
      the solution phase. METHODS: Fluorescence excitation and emission spectra were
      obtained on four polymorphic forms of diflunisal, and on the compound dissolved
      in water. RESULTS: It was found that exciton effects dominate the excitation
      spectra of diflunisal in the four studied polymorphic forms. These phenomena lead
      to a decrease in the energy of the excitation bands relative to that observed for
      the free molecule in fluid solution, and in a splitting of the excitation peak
      into two Davydov components. CONCLUSIONS: The trends in the excitation and
      emission spectra led to the grouping of diflunisal Forms I, II, and III into one
      category, and diflunisal Form IV into a separate category. Because other work has
      established that Form IV is characterized by the highest crystal density and
      consequent degree of intermolecular interaction, the magnitude of the exciton
      coupling can be used to estimate the degree of face-to-face overlap of the
      salicylate-type fluorophores.

PMID- 15948047
TI  - [Palliative care -- a neglected issue in psychosocial research in Germany].

PMID- 15948043
TI  - Spray-dried amorphous solid dispersions of simvastatin, a low tg drug: in vitro
      and in vivo evaluations.
AB  - PURPOSE: To obtain free flowing, stable, amorphous solid dispersions (SDs) of
      simvastatin (SIM), a drug with relatively lower glass transition temperature
      (T(g)) by spray drying technique, and to perform comparative in vivo study in
      rats, which could justify the improvement in rate and extent of in vitro drug
      release. METHODS: Dichloromethane suspensions of SIM either alone or in
      combination with PVP (1:1 or 1:2 parts by weight) were spray dried with proposed
      quantity of Aerosil 200 (1:1, 1:1:1, 1:2:2 parts by weight of SIM, Aerosil 200
      and PVP, respectively). SDs were characterized initially in comparison with pure
      drug and corresponding physical mixtures in same ratios by drug content,
      saturation solubility, SEM, DSC, XRPD, IR, and in vitro drug release. SD 1:2:2
      was further subjected to accelerated stability testing and checked for in vitro
      drug release and presence of crystallinity using DSC and XRPD. In addition,
      improvement in rate and extent of in vitro drug release from SD 1:2:2 was
      justified by in vivo study in rats. RESULTS: Combination of SD and surface
      adsorption techniques has been attempted to overcome the limitations of spray
      drying technique for amorphization of low T(g) drugs. Based on powder
      characteristics, drug content, saturation solubility, and feasibility of
      processing into tablets; SD 1:2:2 was selected as the optimized formulation.
      During initial characterization, SEM, DSC, and XRPD analyses confirmed the
      presence of amorphous form in SD 1:2:2. IR spectroscopy revealed possibility of
      hydrogen bonding interaction between SIM and PVP in SDs. Also, there was
      dramatical improvement in rate and extent of in vitro drug release of SD 1:2:2.
      Insignificant decrease in dissolution was observed with no evidence of
      crystallinity during accelerated stability studies of SD 1:2:2. Moreover in vivo
      study in rats also justified the improvement in therapeutic efficacy of SD 1:2:2
      over pure SIM. CONCLUSIONS: Thus, present study demonstrates high potential of
      spray drying technique for obtaining stable amorphous SDs of low T(g) drugs.

PMID- 15948048
TI  - [Death, euthanasia and end-of-life decisions according to the relatives'
      perspective -- a survey after the death of a close relative].
AB  - Empirical research on euthanasia and medical decisions at the end of life usually
      focus on the doctors' perspective. The perspectives of patients, relatives
      respectively the bereaved families have been neglected so far. The project
      "Patients as partners. Tumour patients and their participation" aims to improve
      the participation of tumour patients in medical decision making at the end of
      life by means of several offerings for patients. In order to develop a
      theoretical model, interviews were conducted with patients, relatives, doctors
      and members of the bereaved families. Between March 2002 and July 2004
      questionnaires were sent to the bereaved families about eight to ten weeks after
      their relatives had perished. Before dying, the patients had been looked after
      and offered consultation by a palliative care team either in hospital or at home.
      RESULTS: Of 151 sent out questionnaires, 59.6 % (n = 90) were filled in and sent
      back by members of the bereaved families. 52.3 % of the patients had died in
      hospital, 33.7 % in their private home. All of the patients who died at home, but
      only one in three patients who died in hospital also wanted to die there. The
      relatives were predominantly very satisfied or satisfied with the medical care
      (67.8 %). 11 % of the bereaved families said, their dying relatives had seriously
      asked for euthanasia. In 74.4 % of all cases, decisions for the renunciation of
      therapy were made, mostly due to a worsening of the general condition (54.4 %) or
      a progress of the disease (46.6 %). CONCLUSION: The questioning was successfully
      conducted. Members of bereaved families are able and also prepared to answer
      questions about the last days of their relatives lives. The question about the
      desired dying place has proved to be workable. In empirical research, the
      perspective of the relatives and bereaved families should be taken in to account
      seriously.

PMID- 15948049
TI  - [Between self-determination and role abdication: opinions about euthanasia --
      results of a study of Thuringians palliative tumour patients].
AB  - This study reports the degree to which terminally ill tumour patients wish to be
      involved in medical decisions about their care and death. In addition, the study
      aimed to examine euthanasia from the patient's perspective. 272 tumour patients
      with a life expectancy of less that 1 year took part in a face to face survey.
      The survey examined attitudes, beliefs and desires with respect to euthanasia,
      where one would like to die and who should be present as well as attitudes to
      advance directives. The majority of tumour patients (75 %) wanted to die at home
      and in the presence of family members (90 %). A multidimensional scaling analysis
      generated two clusters which were interpreted as self-other determination and
      integration-non-integration as a patient within the health system. The central
      theme for the tumour patients is to protect their autonomy in the decision making
      process at the end of their lives. Desires expressed by these tumour patients did
      not reflect public discussions about active, passive or indirect assisted
      suicide. The results demonstrate that doctors should communicate especially
      sensitively with tumour patients and their relatives.

PMID- 15948050
TI  - [The patient and his family].
AB  - Medical decision-making models focus on doctor-patient relationship. The impact
      of the family, specifically the involvement of the relatives in the information-
      and decision-making process have rarely been evaluated yet. Within the project
      "Patient as partners - cancer patients and their involvement in medical decision
      making" progressive disease cancer patients, their relatives and doctors as well
      as Thuringian general practitioners have been interviewed with regard to their
      attitudes (among others) towards the medical system and information and decision
      making processes. RESULTS: From the patient's point of view, the family is highly
      important in decision-making (very important/important 80.3 %). 73 % of the
      patients, but only 58 % of the relatives feel very good/good informed about the
      treatment. With regard to prognosis, 30 % of the patients and 27 % of the
      relatives feel less/poorly informed. 83.7 % of the relatives believe they cannot
      influence treatment decisions. According to this, Thuringian general
      practitioners judge the influence of family members on treatment decisions quite
      low (very high/high 12.9 %, partly 37.4 %, low/not possible 49.7 %), though the
      relatives' wish for involvement is seen quite realistic (89 % of the GP's believe
      that the family wants to be involved). CONCLUSION: From the patients point of
      view, the family has got a high status with regard to medical decision-making. In
      palliative cancer patients doctors should offer an early and continuous
      involvement of relatives in information and decision-making processes in order to
      reduce misjudgements and frustration within the families.

PMID- 15948051
TI  - [Work situation and job satisfaction in an university hospital: development of
      questionnaires for physicians and nurses].
AB  - Aim of the present work was to develop scales for the description of the work
      situation of physicians and nurses. For this purpose a sample of n = 447
      physicians and n = 920 nurses of an University Hospital filled out a new
      conception work situation questionnaire. Further on they got the subscales work
      and profession and financial situation of the Life Satisfaction Questionnaire
      (FLZ). After Principle Component Analysis and item analyses we could develop four
      work situation scales similar for both groups, the physicians and the nurses: 1.
      chief and hierarchy, 2. conflict ability of the team, 3. work conditions at the
      ward and 4. cooperation of the professions. The internal consistencies are medium
      to high with Cronbach's alpha = 0.80-0.90 for the physicians and alpha = 0.83
      0.90 for the nurses. The Work Situation Questionnaire in it's forms for
      physicians (FAA) and for nurses (FAP) are high reliable scales. We also found
      positive validity indications.

PMID- 15948052
TI  - [Report on the 51st Annual Conference of the German College of Psychosomatic
      Medicine, Dresden, March 16.-19. 2005].

PMID- 15948053
TI  - [Quantification of the non-quantifiable: images, imaging, imagination, and the
      real truth].

PMID- 15948054
TI  - Sonography of the neck: current potentials and limitations.
AB  - For many clinical conditions, sonography is the first line imaging modality in
      the evaluation of cervical soft tissue lesions. Cervical cysts, lipomas,
      paragangliomas, neurogenic tumours, haemangiomas or lymphangiomas usually display
      a typical sonographic morphology. Sonography can be used for evaluation of soft
      tissue lesions and cervical lymph node assessment. Most of the afflictions of the
      salivary glands can be diagnosed sonographically. Sonography is also used for
      guided biopsy of lymph nodes, cervical soft tissue tumours or salivary gland
      lesions. The relationship of tumours or lymph nodes to the great cervical vessels
      can be evaluated. Colour Doppler can visualise the vascularisation of cervical
      soft tissue lesions, often narrowing down the differential diagnosis.

PMID- 15948055
TI  - Computerised analysis of liver texture with correlation to needle biopsy.
AB  - AIM: To assist in tissue characterisation for the non-invasive diagnosis of
      diffuse fatty liver infiltration by providing quantitative indices of ultrasonic
      (US) backscatter with correlation to histology. METHODS AND MATERIALS: US images
      from patients referred to US-guided liver needle biopsy (LNB) for persistently
      elevated liver enzymes or serologically positive markers for viral hepatitis were
      recorded. The histopathological reports were reviewed. Steatosis, inflammation
      and degree of fibrosis were scored from 0 (normal) to 3 (severe). Patients with
      level 3 steatosis without inflammation or fibrosis were selected. US images from
      twenty-four healthy subjects served as control. Four textural indices were
      calculated for a selected ROI corresponding to the biopsy site. Sensitivity and
      specificity of discrimination between the two groups were evaluated. RESULTS:
      Fatty and healthy livers formed two distinct clusters. However, in all parametric
      subspaces there was a slight overlap between the groups with a few numbers of
      cases located across the dichotomy line.The sensitivity for all the indices was
      high (90 - 100 %). The specificity for each of the indices was moderate. The co
      occurrence local homogeneity index yielded the highest specificity (88.5 %), with
      a sensitivity equivalent to two of the other indices (90 %). CONCLUSIONS: Highly
      accurate "ultrasonic biopsy" may be obtained for severe fatty liver. The
      described indices can serve as a tool in US computer- aided diagnosis (CAD) of
      diffuse parenchymal liver disease, in particular for severe steatosis of the
      liver.

PMID- 15948056
TI  - Nonspecific granulomatous prostatitis.
AB  - Nonspecific granulomatous prostatitis (NSGP) is a relatively uncommon type of
      chronic inflammation of the prostate, frequently mistaken for carcinoma on
      digital rectal examination, trans-rectal ultrasound (TRUS) and serum PSA test. It
      is presently the most frequent variety of granulomatous prostatitis observed at
      histological examination. The present study reviews the trans-rectal US results
      and serum PSA levels of 20 patients with biopsy-proven NSGP. Physical findings,
      laboratory data and US indicated malignancy in all cases. Sonographically (TRUS),
      the lesions appeared as single or multiple hypoechoic nodules, mainly localised
      in the peripheral zone of the gland, mimicking carcinoma. Mean serum PSA values
      were 13.3 ng/ml (range from 3.5 to 34 ng/ml), and only one patient had a value
      lower than 4 ng/ml. A sufficiently long period of follow-up (mean 19 months;
      range from 7 to 48 months) with TRUS and PSA was only possible in 11/20 patients.
      In 8/11 cases, serum PSA returned within normal range, and in 5/11 patients the
      US features slowly resolved, the hypoechoic nodules disappearing. Final diagnosis
      can only be obtained by prostatic biopsy. Several questions remain unanswered
      regarding the relationship between chronic prostatitis and prostatic carcinoma,
      natural history, the need for specific therapy and also the follow-up of this
      disease.

PMID- 15948057
TI  - [Ultrasound examination of the breast with 7.5 MHz and 13 MHz-transducers: scope
      for improving diagnostic accuracy in complementary breast diagnostics?].
AB  - AIM: Complementary diagnostic methods in early diagnosis of breast cancer are
      used to increase diagnostic accuracy and minimize unnecessary invasive diagnostic
      procedures. Aim of the following prospective, open multicenter clinical study was
      to define the value of high-frequency breast ultrasound with 13 MHZ transducers
      compared to standard breast ultrasound with 7.5 MHz. METHOD: Data of 810 female
      patients, aged 45 to 60 years, with 819 suspicious breast lesions evaluated by
      four participating centres between October 1996 and December 1997. Standardised
      breast ultrasound was performed uniformly using a AU4 IDEA diagnostic ultrasound
      system by Esaote-Biomedica in addition to a standardised procedure of clinical
      examination and standard-2view-mammography. Analysis of all aquired data and the
      correlating histopathological findings was done by means of descriptive
      statistics on the basis of an access datafile (Version 2.0). RESULTS: The
      histopathological evaluation showed 435 benign and 384 malignant findings.
      Overall sensitivity and specificity of the clinical examination were 71.1 % and
      88.9 % and for mammography 84.7 % and 76.5 %, respectively. Standard ultrasound
      with 7,5 MHz reached a sensitivity of 82,6 % and a specificity of 80.8 % high
      frequency ultrasound with 13 MHz came to 87.2 % and 78.4 %, respectively.
      Regarding tumour size, mammography gave the highest sensitivity in detection of
      pre-invasive cancers (DCIS). High-frequency breast ultrasound (13 MHz) proved to
      have a higher diagnostic accuracy compared to standard breast ultrasound (7,5
      MHz) regardless of tumour size. Sensitivity was especially improved in case of
      small invasive tumours (pT1a) with 78 % versus 56 %, respectively. CONCLUSIONS:
      We conclude that high-frequency ultrasound is a valueable additive tool
      especially in the diagnosis of small tumours, improving diagnostic safety and
      reducing unnecessary invasive diagnostic procedures.

PMID- 15948058
TI  - [Sonoanatomy of the muscles and fascia spaces of the pectoral regions].
AB  - BACKGROUND: Aim of the study was to work out a reliable method for the
      ultrasonographic evaluation of the pectoral region. METHODS: The study was
      performed in 20 cadaver specimens and 20 healthy volunteers as well as in 10
      patients with disorders of the pectoral region. RESULTS: For examination of the
      pectoralis major muscle, the landmark for the positioning of the ultrasound
      transducer was found to be the lateral border of the anterior axillary fold in
      the direction of the tip of the coracoid process. Tilting the probe medially, the
      fibres of the pectoralis major muscle become visible in longitudinal alignment.
      The main part of the clavicular portion of the pectoralis major muscle can be
      visualised by moving the probe parallel to this position. Tilting the probe
      downwards, both the internal part of the clavicular portion, the sterno-costal
      and the abdominal portion are evaluated. For examination of the pectoralis minor
      muscle, the probe is positioned between the tip of the coracoid process and the
      sternal angle. Thus the whole muscle can be examined with a single sweep of the
      transducer. In all the specimens, probands and patients of our group, both
      muscle, fascias and pathological lesions could be clearly depicted. SUMMARY:
      Based on the introduction of standard examination planes, the pectoral region can
      be evaluated in detail using ultrasonography. Lesions and pathologic changes can
      be reliably appointed to individual anatomical structures.

PMID- 15948059
TI  - Sonographic imaging of mallet finger.
AB  - Mallet finger is a flexion deformity of the distal interphalangeal joint (DIPJ)
      caused by a disruption of the extensor mechanism. The deformity can b e caused by
      active trauma, minor trauma or other conditions like rheumatoid arthritis or
      osteoarthritis. AIM: To describe the sonographic findings in mallet finger.
      METHOD: We performed sonographic examination on thirty patients with traumatic
      mallet finger, on thirty control patients where we examined the same finger in
      the opposite hand (,) and thirty patients with rheumatoid arthritis or
      osteoarthritis and flexion deformity. RESULTS: We found four criteria for
      traumatic mallet finger which included: discontinuity of the extensor tendon with
      partial or complete tear, avulsion fracture, no real time movements of the
      extensor tendon, and fluid in the region of insertion of the extensor tendon.
      CONCLUSION: Sonographic examination of patients with traumatic mallet finger is
      an important diagnostic tool and can differentiate between traumatic mallet
      finger and flexion deformity of rheumatoid arthritis or osteoarthritis.

PMID- 15948060
TI  - Fitz-Hugh-Curtis-syndrome mimicking acute cholecystitis: value of new ultrasound
      findings in the differential diagnosis.
AB  - Fitz-Hugh-Curtis is a rare syndrome characterised by perihepatitis following
      pelvic inflammatory disease. We report the case of a patient with a right ovarian
      teratoma, abnormal liver tests and pain in the right abdomen and shoulder,
      initially attributed to an acalculous cholecystitis. Before gynaecological
      surgery, a repeat ultrasound scan found several small avascular peritoneal masses
      at the upper dome of the liver, not reported in the initial examination. This
      prompted laparoscopic exploration of the subdiaphragmatic space, and the final
      diagnosis of Fitz-Hugh-Curtis-syndrome was made. Such ultrasound finding appears
      to be a new diagnostic feature of this syndrome.

PMID- 15948061
TI  - Unusual mass in the hepatic portal of an 86-year-old woman.
AB  - Varicose veins in the hepatoduodenal ligament and hepatic portal are normally due
      to cavernous transformation of the portal vein. We present an unusual case of
      varices of the common bile duct in an asymptomatic 86-year-old woman who was
      referred to our hospital for evaluation of a suspected cholangiocarcinoma. A
      cholangiocarcinoma could be excluded, however, and the diagnosis of intramural
      varicosis of the common bile duct was made with transabdominal colour Doppler
      sonography. Sonography showed multiple dilated vessels in the wall of the common
      bile duct. Most patients with choledochal varices are asymptomatic. Choledochal
      varices may, however, result in dilatation of the biliary system, causing raised
      levels of serum alkaline phosphatase and even jaundice.

PMID- 15948062
TI  - [Prenatal diagnosis of right atrial isomerism (asplenia-syndrome): case report].
AB  - Right atrial isomerism (earlier known as asplenia) is a group of malformations
      including anomalies of the heart and the visceral organs. Complex defects of the
      heart are normally found, but these are non-specific. The suspected diagnosis can
      be confirmed most easily by focusing on a specific and segmental examination of
      the heart. We report on a fetus referred at 22 weeks in whom AV-septal defect was
      detected. Heart and stomach were on the left side, but the segmental approach
      allowed the detection of juxtaposed descending aorta and inferior vena cava as
      typical signs of right isomerism. The suspected malformation could be verified by
      the additional detection of infra-diaphragmatic total anomalous pulmonary venous
      drainage by using colour Doppler. Howell-Jolly bodies from fetal blood supported
      the diagnosis of asplenia. Autopsy after termination of pregnancy demonstrated
      the typical signs of right isomerism. The paper reviews the typical prenatal
      findings which lead to the detection of right isomerism in the fetus. Segmental
      approach should be performed in each fetus with an anomaly of the heart
      especially in the presence of complex defects.

PMID- 15948063
TI  - [The evaluation of diagnostic tests].

PMID- 15948065
TI  - [Analysis of the headaches treated in emergency neurology departments].
AB  - INTRODUCTION AND AIMS: Headache is the main cause of visits to the emergency
      neurology department at our hospital. We perform a descriptive analysis of the
      patients who visited the Emergency department because of this pathology and who
      required neurological assessment according to the International Headache
      Society's new classification of headaches. PATIENTS AND METHODS: A retrospective
      study based on 6 months' observation was conducted in order to analyse patients'
      diagnosis, age, sex, recurring visits to the Emergency department, complementary
      tests, day and time of visit to the Emergency service, as well as the destination
      according to their diagnosis. RESULTS: There was a predominance of females
      (56.3%). The most frequent diagnosis is tension-type headache, although patients
      who most often recur are those with the most intense pain (cluster headache) and
      those with some psychiatric disorder. Cranial computerised axial tomography (CAT)
      scans were performed in 44% of cases, and spinal taps in only 8%. Visits are most
      frequent on Mondays. CONCLUSIONS: The percentage of secondary headaches that were
      diagnosed thanks to the presence of an on-call neurologist is very high: 13.36%
      of the evaluations requested. The headaches that most frequently require
      evaluation are generally the most prevalent: migraine without aura and tension
      type headache. The presence of an on-call neurologist reduces the number of
      patients admitted to hospital because of this pathology by over 50%.

PMID- 15948064
TI  - [Evaluation of the diagnostic value of a Spanish adaptation of the Buschke Memory
      Impairment Screen in the detection of dementia and cognitive impairment].
AB  - INTRODUCTION: Screening tests for dementia are a fundamental tool in specialist
      consultation and primary care. The instruments currently used are time-consuming
      and the diagnostic performance they offer is rather poor. The original version of
      the Buschke Memory Impairment Screen (MIS) is a quick simple test with high
      discriminatory power. AIMS: Our aim was to validate a Spanish version of the MIS
      in specialist consultation. PATIENTS AND METHODS: We conducted a prospective
      study in 91 subjects aged over 60 who visited the outpatient department for
      cognitive evaluation. All the patients received a similar diagnostic evaluation
      and the MIS was administered as a blind test. This Spanish version of the MIS was
      produced by means of a cross-cultural adaptation. RESULTS: The area below the ROC
      curve for dementia on the MIS was 0.92, with a similar result for cognitive
      deterioration (CD). A cut-off score of 4 or less offered a sensitivity rate of
      91.9% (CI 95%: 83.4-96.4%) and a specificity level of 81.0% (CI 95%; 70.3-88.6%)
      for the detection of CD. Likewise, a cut-off score of 3 or below presented a
      sensitivity rate of 96.1% (CI 95%: 85.7-99.3%) and a degree of specificity of
      72.6% (CI 95%: 63.2-80.3%) for the detection of dementia. Interobserver and test
      retest reliability (0.85 and 0.81, respectively) were adequate. CONCLUSIONS: This
      version of the Buschke MIS offers a high level of discriminatory power both for
      dementia and for CD, as well as an adequate degree of inter and intraobserver
      reliability within the context of a specialist consultation. Because it is quick
      (less than 4 minutes) and simple to administer, MIS represents a reasonable
      alternative to other screening methods.

PMID- 15948066
TI  - [The anticonvulsive effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline].
AB  - INTRODUCTION: Certain compounds belonging to the family of the 2-aryl oxazolines
      have been reported to act on the central nervous system with a number of
      different effects and applications, which make them useful as depressants,
      anaesthetics, anticonvulsants, and so on. AIMS: Our aim was to study the possible
      effect of 4,4-bis(hydroxymethyl)-2-phenyl-2-oxazoline (OX), obtained by chemical
      synthesis using microwaves, in two experimental models of epilepsy. MATERIALS AND
      METHODS: Two models were used: one involving (repeated stimulation)
      electroconvulsive shock in mice and the other consisted in inducing audiogenic
      seizures in Mongolian gerbils. Recordings were performed of the potentials in the
      dentate gyrus (DG) generated in response to electrical stimulation of the
      entorhinal cortex in anaesthetised gerbils, using the stereotactic technique.
      RESULTS: A 150 mg/kg dose of OX lowered the number of electrical pulses required
      to induce the tonic seizures triggered by the electroshock, as well as their
      duration. This same dose blocked the seizures induced by audiogenic stimuli in
      the gerbils and significantly reduced their severity (degrees of seizures) and
      occurrence. OX diminished, in a dose-dependent manner, the amplitude of the
      excitatory post-synaptic potential and that of the population spike, triggered by
      stimulating the entorhinal cortex in the DG. CONCLUSIONS: OX acts as an
      antiepileptic agent and its mechanism of action could be related to the
      inhibiting effect it exerts on the entorhinal cortex-DG synapses in the
      hippocampus.

PMID- 15948067
TI  - [Intracerebral haemorrhage in a referral hospital in the central-western region
      of Mexico].
AB  - INTRODUCTION: Intracerebral haemorrhage (ICH) has received little attention in
      studies in Mexico. Isolated reports talk of high frequency, its importance as a
      disorder among young people, its being mainly located in the lobar regions and a
      high rate of recurrence. AIMS: The objective of this study was to characterise
      the clinical, radiological, therapeutic and prognostic spectrum of ICH in a
      general hospital in the central-western region of Mexico. PATIENTS AND METHODS:
      The study involved 270 consecutive patients over the age of 15 years with
      spontaneous ICH who were hospitalised in the Neurology and Neurosurgical Service
      in the Antiguo Hospital Civil de Guadalajara between the years 2000 and 2002.
      Their clinical history and progression was known at least on discharge from the
      hospital. RESULTS: The mean age was 63 years (12% under 40 years old) with no
      predominance according to gender (53% males). Arterial hypertension was the main
      risk factor in 69%, followed by obesity in 38%. There were no differences in the
      Glasgow administered on admission in three pre-established subgroups. The ICH was
      ganglionic in 64% of cases and lobar in 24%. Arterial hypertension was the
      principal cause of ICH in 76%. Ventricular aperture was noted in 53%. All the
      patients were treated in a general ward. Mortality in the acute phase occurred in
      49%, although a poor progression was observed in 83%. Overall recurrence was 13%.
      Outpatient follow-up was poor. CONCLUSIONS: ICH shares most of the features
      reported in Anglo-Saxon series including aetiology and location. In our
      population, mortality and recurrence are high with important sequelae. The high
      frequency of ICH (40%) may represent a bias in the selection of hospitals.

PMID- 15948068
TI  - [Infiltration of the meninges or brain by a non-Hodgkin's lymphoma, diagnosed by
      flow cytometry in cerebrospinal fluid].
AB  - INTRODUCTION: Two forms of growth are reported in the neuroradiology of cerebral
      lymphomas: mass, single or multiple lesions, with homogeneous contrast
      enhancement, and diffuse infiltration. Flow cytometry enables us to diagnose non
      Hodgkin's lymphoma, when clonality of B cells is detected. It is usually employed
      with peripheral blood or bone marrow samples but can be used with cerebrospinal
      fluid (CSF). CASE REPORT: We report the case of a 68-year-old female, who was
      admitted to hospital because of rapidly progressive onset of confusion and right
      side hemiparesis that developed in a matter of days. Magnetic resonance imaging
      (MRI) of the head showed a diffuse infiltrative lesion, without contrast
      enhancement, which covered the left basal nuclei, the left frontal white matter,
      the genu of the corpus callosum and the right frontal white matter. The CSF
      showed slight pleocytosis (20 cells/mL) and a notable degree of hypoglycorrhachia
      (10 mg/dL). The cytological examination only revealed lymphocytes, with no data
      indicating atypicality. The flow cytometry assay detected large mononuclear B
      cells, with the CD19 + CD20 + CD10-lambda phenotype, which is characteristic of
      diffuse non-Hodgkin's lymphoma of large B cells. The clinical course ran quickly
      towards a fatal outcome; it progressed to left-side hemiplegia and coma, and the
      patient died two weeks after admission to hospital. CONCLUSIONS: In cases of
      cerebral lymphoma, especially when the neuroradiological pattern displays diffuse
      infiltration and there are anomalies involving CSF, the flow cytometry in CSF can
      be diagnostic, thus avoiding the need for other invasive brain procedures to deal
      with lesions that are usually located deep inside the brain at badly defined
      sites.

PMID- 15948069
TI  - [Vein of Galen arteriovenous malformations and neonatal convulsions].
AB  - INTRODUCTION: Vein of Galen arteriovenous malformation (VGAM) appears during the
      embryonic period and gives rise to a complex network of arterial and venous
      vessels that generates a blood shift, from the brain parenchyma towards the
      malformation, with haemodynamic repercussions. Heart failure is the most frequent
      presenting symptom during the neonatal period, yet, convulsions or other
      neurological signs have occasionally been reported in this stage of life. CASE
      REPORT: A term infant with symptoms of heart failure and convulsions that began
      during the first 12 hours of life. CAT and magnetic resonance angiography scans
      revealed a vascular malformation and areas of cerebral ischaemia. CONCLUSIONS: In
      the case of our patient, detecting areas of ischaemia in the cerebral hemispheres
      suggested that the damage could be caused by a "steal" syndrome leading the blood
      flow away from these areas towards the malformation. This situation can occur
      either before or after birth and the self-limiting nature of the seizures in
      cerebral infarcts could lead to them going noticed because they take place inside
      the uterus or when the patient is not being observed directly by his or her
      health care providers. We suspect that the convulsions in newborn infants with
      this malformation may well be more frequent than is currently believed.

PMID- 15948070
TI  - [Pontine stroke secondary to a foramen magnum meningioma].
AB  - INTRODUCTION: Meningioma is one of the most frequent tumours affecting the
      central nervous system, with an estimated incidence of between 15 and 20% of all
      brain tumours. They are generally benign and slow growing. Their appearing as a
      cerebral infarction is very rare. CASE REPORT: A right-handed 75-year-old female
      patient with a personal history of arterial hypertension, who visited the
      Emergency Department because of the sudden onset of severe dysarthria,
      accompanied by loss of strength in the left limbs, supranuclear facial palsy on
      the left side and Horner syndrome on the right. A computerised tomography scan of
      the brain revealed a lacunar infarct in said location, with no other appreciable
      damage. The neurovascular study included a transcranial Doppler, which was unable
      to insonate the left vertebral artery or the basilar artery. Magnetic resonance
      imaging of the head revealed a foramen magnum meningioma, with vertebrobasilar
      vascular distortion. The patient progressed favourably and was submitted to
      radiosurgery. CONCLUSIONS: The case reported here is unique, since it describes a
      meningioma of the posterior fossa that appears in the form of the initial
      symptoms of a pontine stroke due to a vascular disorder.

PMID- 15948071
TI  - [FOXP2: from the specific disorder to the molecular biology of language. I.
      Aetiological, neuroanatomical, neurophysiological and molecular aspects].
AB  - INTRODUCTION: The task of cloning the genes whose products are involved in the
      organisation and functioning of the nerve centres that enable language tasks to
      be executed must necessarily start with the identification and the cognitive,
      linguistic, neuroanatomical and neurophysiological analysis of individuals with
      hereditary (specific) language impairment (SLI). DEVELOPMENT: The first of these
      genes to be characterised in this way--a gene called FOXP2--codes for a
      regulating factor that acts as a transcriptional repressor in the central nervous
      system. It is expressed in neuronal populations mainly situated in the basal
      ganglia, but also in the cortex, cerebellum and the thalamus, which are
      presumably involved in the development and/or functioning of the thalamic
      cortical-striatal circuits associated with motor planning and learning. The
      protein FOXP2 shows several structural patterns that, when altered in other
      proteins, also give rise to different disorders in the central nervous system.
      The pattern of expression of the gene is preserved phylogenetically, although
      this does not happen in the case of the pattern of mRNA maturation. In
      individuals with a mutated version of FOXP2, morphological and functional
      anomalies are detected in those areas in which the gene is expressed. These
      abnormalities can be correlated satisfactorily with the phenotypic
      characteristics of the disorder, which are at the same time of both a motor and
      linguistic nature. CONCLUSIONS: The fact that other variations of SLI are not
      linked to the FOXP2 gene raises the need for further research into the genetic
      bases of the disorder, while also suggesting that it would be advisable to
      reassess the phenotypic scope of the variant associated to the mutation of this
      gene.

PMID- 15948072
TI  - [The Andalusia Epilepsy Society's Guide to Epilepsy Therapy 2005: III.
      Antiepileptic therapy in special situations].
AB  - AIMS: The objective of this work was to produce a scientific evidence-based guide
      to clinical practice dealing with the basic questions concerning the treatment of
      epilepsy. DEVELOPMENT: A committee of 11 experts belonging to the Andalusia
      Epilepsy Society, made up of six neurologists, three neuropaediatricians, one
      neurosurgeon and a pharmacologist, all of whom were deeply involved and
      experienced in epilepsy, conducted a thorough review of the literature in search
      of all the evidence available on the proposed subject matter. The following
      databases were used: MEDLINE, Cochrane Library and the databases of several
      clinical practice guidelines (National Guideline Clearinghouse, National
      Institute of Clinical Excellence and the American Academy of Neurology's Clinical
      Guidelines). The Guide was set out in seven sections and was published in four
      parts. From a total number of 187 relevant documents, the committee found 63
      examples of scientific evidence and 91 therapeutic recommendations. These were
      tabulated and classified according to the European Federation of Neurological
      Societies' criteria for producing Clinical Practice Guidelines. CONCLUSIONS: The
      results of this survey provide scientific evidence-based clinical guidelines that
      are useful, simple and applicable at different levels of health care.

PMID- 15948073
TI  - [The work of Santiago Ramon y Cajal in the Revista Trimestral Micrografica
      (Trabajos del Laboratorio de Investigaciones Biologicas)].
AB  - AIM: This paper is based on a study of Revista Trimestral Micrografica (Trabajos
      del Laboratorio de Investigaciones Biologicas) between its creation by Santiago
      Ramon y Cajal in 1896 and his death in 1934. DEVELOPMENT: The journal Revista
      Trimestral Micrografica was the main way in which Santiago Ramon y Cajal and his
      school published their work since its creation. Ramon y Cajal created the journal
      for two main reasons: first, he needed a rapid system to publish his own work;
      second, the journal could serve to encourage his pupils. The journal published
      many important reports defending the neuronal theory which expanded the cellular
      one to include the nervous system.

PMID- 15948074
TI  - [Cerebral venous thrombosis and inflammatory bowel disease].

PMID- 15948075
TI  - [Neurovascular study in paresis of the ocular motor nerves].

PMID- 15948077
TI  - [Cauda equina paraganglioma].

PMID- 15948080
TI  - Low-to-moderate alcohol intake and health status in heart failure patients.
AB  - BACKGROUND: Although heart failure (HF) guidelines recommend alcohol abstinence,
      existing evidence indicates that alcohol may not worsen survival and no data
      about associations between alcohol and health status (patients' symptoms,
      function, and quality of life) exist. METHODS AND RESULTS: Alcohol use was
      quantified in 420 HF outpatients. The associations between moderate alcohol
      intake (1 to 60 drinks/month) and health status were assessed by comparing
      baseline and 1-year Kansas City Cardiomyopathy Questionnaire (KCCQ) and Short
      Form-12 (SF-12) scores between moderate and nondrinkers. No differences in
      baseline KCCQ or SF-12 scores between abstainers (n = 245) and moderate drinkers
      (n = 175) were observed (KCCQ 60.5 +/- 24 versus 61.9 +/- 23.5, P = .55; SF-12
      Physical Component Score (PCS) 33.6 +/- 11.2 versus 35.3 +/- 10.2, P = .14; and
      SF-12 Mental Component Score (MCS) 49.1 +/- 11.1 versus 49.4 +/- 11.4, P = .78).
      Abstainers and drinkers also had similar 1-year KCCQ scores (65.8 +/- 24.5 versus
      69.3 +/- 24.1, P = .23), mortality (10.5% versus 11.6%, P = .72) and HF
      hospitalizations (18.0% versus 15.4%, P = .51). Multivariable analyses
      controlling for baseline differences also revealed similar outcomes between
      abstainers and drinkers-1-year KCCQ change = 4.3 +/- 1.8 versus 5.2 +/- 2.5; P =
      .75), mortality (OR = 1.33, 95% CI 0.67-2.64), or HF hospitalization (OR = 1.13,
      95% CI 0.60-2.11). CONCLUSION: No relationships between moderate alcohol
      consumption and health status or 1-year outcomes were identified in this
      multicenter observational study. These data do not support the need for complete
      alcohol abstinence for all HF patients among those who drink in moderation.

PMID- 15948081
TI  - Alcohol consumption and heart failure.

PMID- 15948082
TI  - Effects of beta-blocker therapy on ventilatory responses to exercise in patients
      with heart failure.
AB  - BACKGROUND: Ventilatory efficiency is the increase in ventilation relative to
      carbon dioxide production during exercise. Congestive heart failure (CHF) is
      associated with decreased ventilatory efficiency. beta-blockers improve
      hemodynamics, prolong survival, and improve functional class in patients with
      CHF, though peak exercise performance may not improve. We hypothesized beta
      blockers increase ventilatory efficiency in patients with CHF. METHODS AND
      RESULTS: The study group comprised 614 subjects with left ventricular ejection
      fraction < or = 40% referred for cardiopulmonary exercise testing. Clinical and
      exercise data were reviewed and recorded. For comparison, subjects were divided
      into those treated with beta-blockers (n = 195) and those not treated (n = 419).
      Subjects on beta-blockers had lower minute ventilation (12 +/- 4 versus 14 +/- 4
      L/min, P < .001) at rest, which remained lower during submaximal and maximal
      exercise, by 4 and 6 L/min, respectively (P = .001). Ventilatory efficiency was
      increased in subjects treated with beta-blockers at submaximal (32 +/- 6 versus
      34 +/- 7, P = .002) and maximal (34 +/- 7 versus 37 +/- 10, P = .005) exercise.
      Differences between treatment subgroups remained significant by covariate
      analysis; beta-blockers were also independently associated with decreased minute
      ventilation by multiple regression. CONCLUSION: Beta-blockers may be associated
      with increased ventilatory efficiency in CHF patients, which may contribute to
      improved functional class and quality of life.

PMID- 15948083
TI  - Beta-blockers, exercise, and ventilation in chronic heart failure.

PMID- 15948084
TI  - Subvalvular alterations promote increased mitral valve regurgitation in
      progressive dilated cardiomyopathy.
AB  - BACKGROUND: Alterations in transmitral pressure, valve structure, subvalvular
      geometry, and abnormal myocardial function have all been implicated in the
      pathophysiology of functional/progressive mitral valve regurgitation (MR). In
      this study, we hypothesized that a relatively small structural lesion to the
      mitral valve apparatus predisposes to severe MR in the setting of progressive
      left ventricular dilation. While examining this hypothesis, an additional purpose
      of this study was to determine the extent of papillary muscle (PM) distortion and
      mitral annular dilation with increasing MR resulting from progressive dilated
      cardiomyopathy. METHODS AND RESULTS: Mild MR was produced via a limited, fixed
      structural lesion to the mitral valve apparatus of 8 dogs (20 to 22 kg).
      Incremental tachypacing induced left ventricular dilation over an 8-month period.
      The pacer was deactivated and the dogs followed for an additional 6 weeks.
      Echocardiographic measurements demonstrated significant cardiac remodeling (left
      ventricular end diastolic diameter) and MR progression with a 54% increase in
      left ventricular end diastolic diameter and a 44% increase in MR jet area (P <
      .05). Tachypacing induced decreases in left ventricular ejection fraction
      recovered nearly to baseline levels by 6 weeks after pacing cessation.
      Nevertheless, left ventricular dilation persisted and MR remained severe after
      pacing cessation. There was a significant increase in the short axis PM segment
      length and PM angular separation from baseline (6.28 +/- 0.83 versus 4.02 +/-
      0.56 cm and 99.7 +/- 2.6 versus 90.1 +/- 3.2 deg, respectively, P < .05) with no
      change in mitral annulus circumference (8.71 +/- 0.70 versus 8.15 +/- 0.35 cm, P
      = NS). CONCLUSION: Progressive MR severity in nonischemic dilated cardiomyopathy
      resulted from changes in left ventricular shape and altered papillary muscle
      geometries and does not require mitral annulus dilation or a reduced left
      ventricular ejection fraction.

PMID- 15948085
TI  - Impaired vasoreactivity in end-stage heart failure patients on intravenous
      inotropic support.
AB  - BACKGROUND: Vasoreactivity is known to be impaired in heart failure patients;
      however, it has not been determined whether standard medical therapy for end
      stage heart failure patients (ES-HF) ameliorates this impairment. Therefore, we
      sought to investigate flow-mediated dilation (FMD) responses in ES-HF with normal
      or near normal cardiac indices from continuous inotropic support. METHODS AND
      RESULTS: Vascular ultrasound was used to assess FMD responses to isometric
      exercise and cuff occlusion in 15 ES-HF patients and 5 control subjects (C). ES
      HF patients had significant hyperemic response to maximal exercise (P < .05),
      which was blunted relative to C (ES-HF; 84 +/- 21 mL/min versus C; 299 +/- 85
      mL/min, P < .05). ES-HF patients did not show a significant hyperemic response to
      submaximal exercise. C had a significant increase in arterial diameter that
      exceeded ES-HF after both maximal (C; 8 +/- 1% versus. ES-HF; -0.9 +/- 0.86%, P <
      .05) and submaximal exercise (C; 6 +/- 1% versus ES-HF; 0.57 +/- 1%, P < .05).
      FMD responses at similar absolute workloads showed that both the mean hyperemic
      response and the change in arterial diameter were significantly greater in C.
      After cuff occlusion, the mean hyperemic response for ES-HF was again
      significantly blunted compared with C (ES-HF; 117 +/- 26% versus C; 352 +/- 86%,
      P < .05). After cuff occlusion, arterial diameter in C significantly increased in
      response to hyperemia, whereas ES-HF patients had a paradoxical vasoconstrictive
      response (C; 10.7 +/- 1.1% versus ES-HF; -5.3 +/- 1.5%, P < .05). CONCLUSION:
      Peripheral vasoreactivity in response to either maximal exercise, submaximal
      exercise, or hyperemic stimuli is impaired in ES-HF patients with normal resting
      cardiac outputs.

PMID- 15948086
TI  - Randomized trial of a nurse-administered, telephone-based disease management
      program for patients with heart failure.
AB  - BACKGROUND: Heart failure is a common and important cause of morbidity and
      mortality. Disease management offers promise in reducing the need for
      hospitalization and improving quality of life for heart failure patients, but
      experimental data on the efficacy of such programs are limited. METHODS AND
      RESULTS: A total of 151 patients hospitalized with heart failure were randomized
      to usual care or scheduled telephone calls by specially trained nurses promoting
      self-management and guideline-based therapy as prescribed by primary physicians.
      Nurses also screened patients for heart failure exacerbations, which they managed
      with supplemental diuretics or by contacting the primary physician for
      instructions. Outcomes included time to hospital encounter, mortality, number and
      cost of hospitalizations, functional status, and satisfaction with care.
      Intervention patients had a longer time to encounter (hazard ratio [HR] = 0.67;
      95% confidence interval [CI] 0.47-0.96; P = .029), hospital readmission (HR =
      0.67; CI 0.46-0.99; P = .045), and heart failure-specific readmission (HR = 0.62;
      CI 0.38-1.03; P = .063). The number of admissions, hospital days, and hospital
      costs were significantly lower during the first 6 months after intervention but
      not at 1 year. The intervention had little effect on functional status,
      mortality, and satisfaction with care. CONCLUSION: A nurse-administered,
      telephone-based disease management program delayed subsequent health care
      encounters, but had minimal impact on other outcomes.

PMID- 15948087
TI  - Validity of pedometers for measuring exercise adherence in heart failure
      patients.
AB  - BACKGROUND: Measuring adherence to exercise is important to clinicians and
      researchers because inadequate adherence can adversely affect the effectiveness
      of an exercise program and cloud the relationship between exercise and clinical
      outcomes. Hence, assessment strategies for adherence to exercise, as with
      assessment strategies for other outcomes, must have demonstrated validity if they
      are to be employed with confidence. We conducted this study to determine the
      validity of pedometers as a measure of exercise adherence to a home-based walking
      program in heart failure patients. METHODS AND RESULTS: Exercise adherence was
      measured using pedometers in 38 patients (74% men) age 54.1 +/- 11.7 years who
      participated in a 12-month home-based walking program. A comparison of functional
      status as measured by the 6-minute walk distance and peak oxygen uptake (VO2 max)
      at 6 months into the exercise training program was made between 2 groups of
      participants who were thought to represent adherers and nonadherers: participants
      who demonstrated > or = 10% change in pedometer scores (n = 20) and those who
      showed no change in pedometer scores (n = 18) from baseline to 6 months. Patients
      who showed improvements in their pedometer scores over 6 months had better
      functional status at 6 months (6-minute walk distance 1718 +/- 46 versus 1012 +/-
      25 meters, F = 5.699, P = .022; VO 2 max 17 +/- 0.7 versus 10 +/- 0.5 units, F =
      7.162, P = .011) when compared with patients whose pedometers reflected minimal
      change in distance walked (ie, < or = 10%). CONCLUSION: Pedometers are
      inexpensive and readily available to both clinicians and researchers. The results
      of this study suggest that they may be a valid indicator of exercise adherence in
      heart failure patients who participate in a home-based walking program.

PMID- 15948088
TI  - Testing a published model of health-related quality of life in heart failure.
AB  - BACKGROUND: Health-related quality of life (HRQOL) in patients with heart failure
      is compromised and associated with increased mortality and rehospitalization.
      Inadequate conceptualization of variables related to HRQOL has hampered
      clinicians' efforts to enhance HRQOL. The purpose of this study was to test the
      Wilson and Cleary model (WCM) of HRQOL in patients with heart failure. METHODS
      AND RESULTS: Data from 293 patients with heart failure were analyzed to determine
      the best multivariate HRQOL model given variables derived from WCM. HRQOL was
      measured using the Minnesota Living with Heart Failure Questionnaire (MLHFQ).
      Health perception, symptom status, and age predicted the total MLHFQ (P < .0001)
      and the emotional scale (P < .0001), and health perception, symptom status, New
      York Heart Association predicted the physical scale (P < .0001). Health
      perception was a mediator of the effect of symptom status on HRQOL. Functional
      status was not a mediator of the effect of symptom status on health perception.
      CONCLUSION: The most influential variables associated with HRQOL were the
      subjective variables: health perception and symptom status. Objective variables
      proposed by WCM to drive the model were not significant predictors. Mediator
      effects hypothesized in the WCM were not fully demonstrated in this sample. Thus
      modification of the WCM is warranted.

PMID- 15948089
TI  - The Na+/Ca2+ exchanger/SR Ca2+ ATPase transport capacity regulates the
      contractility of normal and hypertrophied feline ventricular myocytes.
AB  - BACKGROUND: Pressure overload leads to cardiac hypertrophy, which is often
      followed by heart failure. We tested the hypothesis that depressed contractility
      in this process results from an imbalance in Ca 2+ transport by the sarcoplasmic
      reticulum (SR) Ca2+ ATPase (SERCA) and the sarcolemmal Na+/Ca2+ exchanger (NCX).
      METHODS AND RESULTS: Left ventricular (LV) myocytes (n = 79) from 12 normal (N)
      and 5 hypertrophied (LVH, by aortic banding) feline hearts were studied.
      Adenoviral gene transfer was used to introduce green fluorescent protein (GFP),
      SERCA2, and NCX into N and LVH myocytes. Contraction (videomicroscopy) and Ca2+
      transients (Fluo-3) were measured in steady state and after rest periods of 2 to
      120 seconds (rest decay and potentiation). LVH hearts were significantly larger
      than N (7.1 +/- 1.4 versus 4.2 +/- 0.2 g/kg). SERCA protein was significantly
      less abundant in LVH versus N. Steady state contractions and Ca2+ transients of
      LVH-GFP myocytes decayed more slowly and rest decay of contractility was more
      pronounced compared with N-GFP. Infection of LVH (and N) myocytes with SERCA
      increased basal contractility and reduced rest decay. Infection of LVH myocytes
      with NCX almost abolished contraction and in N myocytes reduced contractility and
      increased rest decay. CONCLUSION: These findings suggest that an imbalance of
      Ca2+ transport by SERCA and the NCX produces the characteristic contractile
      abnormalities of hypertrophied cardiac myocytes.

PMID- 15948090
TI  - Alterations of alpha-adrenergic modulations of coronary microvascular tone in
      dogs with heart failure.
AB  - BACKGROUND: It remains unclear whether coronary microvascular response to alpha
      adrenergic activation alters in chronic heart failure (CHF). METHODS AND RESULTS:
      We investigated the alpha-adrenergic receptor-mediated effects on coronary
      pressure-flow relationship (CPFR) in a tachycardia-induced canine heart failure
      model. The dogs studied were male (29 of 31) and the drugs were given
      intracoronary. The slope of CPFR during long diastole was evaluated as an index
      of coronary vascular resistance, during alpha1- or alpha2-adrenergic stimulation
      or inhibition under anesthesia in the baseline and failing state after 3 weeks of
      rapid ventricular pacing. Resting coronary blood flow and CPFR did not change in
      the failing state from the baseline state. Neither alpha1 nor alpha2 stimulation
      changed the slope of CPFR in the baseline state. However, in the failing state,
      alpha1 stimulation decreased the slope of CPFR by 23 +/- 5% (P < .05), whereas
      alpha2 stimulation increased it by 73 +/- 10% (P < .05), which was nearly
      abolished by pretreatment with NG-nitro-L-arginine methyl ester. CONCLUSION:
      Alpha2-mediated vasodilatory action, presumably via endothelium-derived nitric
      oxide release, would be enhanced in the coronary microvascular bed, which may
      antagonize enhanced alpha1-induced vasoconstriction in CHF.

PMID- 15948091
TI  - Clinical and analytical considerations in the study of health status in device
      trials for heart failure.
AB  - BACKGROUND: Measures of health status (including symptoms, functional status, or
      quality of life) assess patients' experiences of their disease, and may therefore
      be used to quantify the benefits and risks of treatment. The aim of this article
      is to provide recommendations to regulatory agencies and research sponsors
      regarding the use of health status measures in medical device trials. METHODS AND
      RESULTS: A workshop jointly planned by the Heart Failure Society of America and
      the US Food and Drug Administration was convened in October 2003 in Washington,
      DC. A Working Group to address health status measures initiated its collaboration
      at the workshop and continued its efforts throughout the next year. The Working
      Group recommended assessment of health status in all studies of heart failure
      therapy. Standardized instruments known to be valid, reliable, responsive to
      changes, and available in the languages of target populations should be used.
      Minimizing bias may be accomplished by using blinded, independent evaluators;
      collecting multiple health status measures; using valid statistical methods; and
      creating a health status resource bank. CONCLUSION: Assessment of health status
      should be part of any device trial and should occur regardless of whether the
      device is intended as destination or bridging therapy. Health status endpoints
      should be chosen, collected, and analyzed with the same level of scientific rigor
      as traditional clinical endpoints. Regulatory agencies should require use of
      analytic methods that handle the complexity of health status data in addition to
      usual protocol protections.

PMID- 15948094
TI  - The effects of ejection fraction on N-terminal ProBNP and BNP levels in patients
      with acute CHF: analysis from the ProBNP Investigation of Dyspnea in the
      Emergency Department (PRIDE) study.
AB  - BACKGROUND: Limited data exist regarding the impact of left ventricular ejection
      fraction (LVEF) on N-terminal pro-brain natriuretic peptide (NT-proBNP) and B
      type natriuretic peptide (BNP) levels in patients with acute congestive heart
      failure (CHF). METHODS AND RESULTS: LVEF data were analyzed for 153 subjects with
      acute CHF. LVEF > or =50% was defined as non-systolic CHF (NS-CHF); LVEF >50% was
      defined as systolic CHF (S-CHF). 76 subjects (49.7%) had NS-CHF. Median NT-proBNP
      and BNP levels were significantly higher among patients with S-CHF (6196 pg/mL,
      592 pg/mL, respectively) compared with those patients with NS-CHF (2849 pg/mL,
      259 pg/mL, respectively). With optimal cut-points, a false-negative rate of 7%
      was observed for both assays among patients with S-CHF. Among patients with NS
      CHF, BNP had a significantly higher false-negative rate (20%) than did NT-proBNP
      (9%; P < .001 for difference). NT-proBNP, but not BNP, significantly correlated
      with CHF symptom severity among patients with NS-CHF. CONCLUSION: Levels of both
      NT-proBNP and BNP are significantly lower in patients with NS-CHF; however, in
      contrast to NT-proBNP, BNP may be falsely negative in up to 20% of patients with
      NS-CHF and does not correlate with symptom severity in NS-CHF. NT-proBNP appears
      superior to BNP for the evaluation of suspected acute CHF in patients with
      preserved LVEF.

PMID- 15948093
TI  - NT-ProBNP reduction percentage during admission for acutely decompensated heart
      failure predicts long-term cardiovascular mortality.
AB  - BACKGROUND: N-terminal brain natriuretic peptide (NT-proBNP) improves emergency
      room diagnosis of acutely decompensated heart failure. Less evidence is available
      on the usefulness of NT-proBNP as a prognostic marker after hospitalization for
      acute heart failure. The percentage of NT-proBNP reduction during admission and
      its prognostic significance were studied. METHODS AND RESULTS: This was a
      prospective study of 74 patients in the emergency department who were diagnosed
      with acute heart failure and who had follow-up evaluation for 6 and 12 months
      after admission. Plasma NT-proBNP concentrations were measured on admission, at
      24 hours, at day 7, and at 6 and 12 months. Eighteen patients died during the 12
      month follow-up; 12 deaths were from cardiovascular causes. NT-proBNP
      concentrations were significantly higher in the emergency department and at 24
      hours than those concentrations that were found at day 7 and beyond (P < .001).
      During admission, the NT-proBNP concentration fell a mean of 15% in patients who
      died of cardiovascular causes during the 1-year follow-up evaluation, in 75% in
      those patients who died of non-cardiovascular causes, and in 50% in survivors (P
      = .004). The area under the receiver operator characteristic curve for NT-proBNP
      reduction percentage to predict cardiovascular death was 0.78 (95% CI, 0.66-0.90;
      P = .002). A 30% NT-proBNP reduction percentage cutoff value had 75% accuracy for
      the identification of high-risk patients and was the only variable that was
      associated with cardiovascular death in multivariate analysis (odds ratio, 4.4;
      95% CI, 1.12-17.4; P = .03). CONCLUSION: NT-proBNP reduction percentage during
      admission for acutely decompensated heart failure appeared to be the best
      predictor of cardiovascular death during the follow-up period. A <30% NT-proBNP
      reduction percentage identified a subgroup of high-risk patients.

PMID- 15948095
TI  - Diagnostic and prognostic performance of N-terminal ProBNP in primary care
      patients with suspected heart failure.
AB  - BACKGROUND: The value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in
      terms of diagnosis and prognosis in congestive heart failure (CHF) and left
      ventricular systolic dysfunction (LVSD) has been demonstrated previously in
      various populations, but data on primary care patients are sparse. The aim of
      this study was to evaluate the diagnostic and prognostic performance of NT-proBNP
      in primary care patients with suspected CHF. METHODS AND RESULTS: Three hundred
      sixty-seven consecutive patients (mean age, 68.8 years; range, 39.0-84.0 years)
      who had been referred by their general practitioner for echocardiographic
      evaluation because of suspected CHF. In all patients, NT-proBNP was measured at
      baseline and left ventricular ejection fraction (LVEF) was estimated with
      echocardiography. LVSD (LVEF < or =0.40) was found in 9% of the patients. NT
      proBNP was significantly higher in patients with LVSD (P < .0001). With
      predefined cut off values for NT-proBNP (125 pg/mL), the sensitivity,
      specificity, positive predictive value, and negative predictive value for the
      detection of LVSD were 0.97, 0.46, 0.15 and 0.99, respectively. Area under the
      receiver operating characteristic curve was 0.87. The application of an age
      differentiated cut-off value for NT-proBNP (125 pg/mL for <75 years old and 450
      pg/mL for > or =75 years old) did not increase diagnostic performance. Patients
      were followed for a median of 778 days; 8% of the patients died during the follow
      up period. The mortality rate was higher in patients with NT-proBNP of >125 pg/mL
      than in patients with normal values (P < .002, log rank), and the difference
      persisted after controlling for age, gender, and LVEF (hazard ratio per unit
      increase in log NT-proBNP, 2.2; range, 1.2-4.1; P = .015). CONCLUSION: In primary
      care patients who were referred for echocardiography because of suspected CHF, NT
      proBNP values <125 pg/mL effectively rule out LVSD. Furthermore low NT-proBNP
      values are associated with a lower risk of death, independently of age, gender,
      and LVEF.

PMID- 15948096
TI  - NT-ProBNP in outpatients after myocardial infarction: interaction between
      symptoms and left ventricular function and optimized cut-points.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) allows us to
      rule out left ventricular dysfunction (LVD) in the general population at a
      recommended cut-off concentration of 125 pg/mL. It was our objective to reassess
      this cut-point in outpatients after myocardial infarction. METHODS AND RESULTS:
      NT-proBNP was assessed in 418 randomly selected outpatients who had experienced
      myocardial infarction and 352 siblings who had not experienced myocardial
      infarction (control). Left ventricular ejection fraction (LVEF) and mass-index
      (LVMI) were assessed by echocardiography. NT-proBNP was elevated in outpatients
      after myocardial infarction (mean [+/-SEM], 305 +/- 25 pg/mL vs control, 84 +/- 8
      pg/mL; P < .01) and was correlated inversely with LVEF ( P < .001). When patients
      were stratified according to the presence or absence of heart failure, NT-proBNP
      was elevated significantly throughout all LVEF strata (each P < .05). On
      regression analysis, NT-proBNP was correlated independently with LVEF, LVMI,
      heart failure, and glomerular filtration rate (all P < .01). In patients with
      heart failure, the optimal cut-point for the detection of an LVEF <35% was 348
      pg/mL (sensitivity 80%; specificity 69%) and for the detection of an LVEF <45%
      was 260 pg/mL (sensitivity 60%; specificity 60%). The relative risk for LVD in
      the presence of elevated NT-proBNP increased from 2.7 to 7.7 (EF < 35%) and from
      1.4 to 2.4 (EF < 45%) when these cut-points were applied instead of the 125 pg/mL
      cut-point. An LVEF of <35% could be ruled out in symptomatic outpatients after
      myocardial infarction with a negative predictive value of 97% (cut-point 348
      pg/mL) and in asymptomatic outpatients after myocardial infarction with a
      negative predictive value of 98% (cut-point 157 pg/mL). CONCLUSION: NT-proBNP is
      higher in outpatients after myocardial infarction than in the general population.
      In symptomatic patients, a cut-point of 348 pg/mL yields satisfactory sensitivity
      and specificity for the detection of significant LVD (EF < 35%). Furthermore,
      significant LVD can be virtually ruled out in symptomatic and asymptomatic
      outpatients after myocardial infarction at below-threshold concentrations.

PMID- 15948097
TI  - Elevated NT-ProBNP levels in patients with increased left ventricular filling
      pressure during exercise despite preserved systolic function.
AB  - BACKGROUND: The role of brain natriuretic peptides in the detection of mild forms
      of isolated diastolic dysfunction is still uncertain. We therefore investigated
      the plasma levels of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in
      patients with heart failure symptoms during exercise, despite preserved systolic
      cardiac function. METHODS AND RESULTS: Fifteen control subjects and 15
      symptomatic patients with preserved left ventricular ejection fraction of > or
      =50%, near normal Doppler echocardiographic indices, and left and right heart
      catheter indices at rest but increased filling pressures during exercise were
      studied. Plasma NT-proBNP levels and surrogate parameters of diastolic function
      were determined simultaneously. The median NT-proBNP plasma level was elevated
      (median, 145.2 pg/mL [range, 69.7-273.4 pg/mL] vs 38.3 pg/mL [range, 22.1-64.7
      pg/ml]; P < .0001) in patients with increased filling pressure during exercise
      and correlated strongly with the pulmonary capillary wedge pressure (r = 0.78; P
      < .001). CONCLUSION: NT-proBNP levels are increased in patients with increased
      filling pressures during exercise and useful for the detection of diastolic
      dysfunction in patients with exertional dyspnea.

PMID- 15948098
TI  - Guiding and monitoring of heart failure therapy with NT-ProBNP: concepts and
      clinical studies.
AB  - BACKGROUND: Since 1988 with the discovery of B-type natriuretic peptide (BNP),
      many reports have confirmed the elevation of plasma BNP in symptomatic heart
      failure and confirmed that plasma levels are an independent predictor of death
      and cardiovascular events in both acute and chronic heart failure. METHODS AND
      RESULTS: A more slender evidence base attests that knowledge of plasma BNP levels
      can be used to produce clinical benefit. One randomized controlled trial
      demonstrated that measurements of N-terminal pro-brain natriuretic peptide (NT
      proBNP) can be used to improve diagnostic accuracy in patients with heart failure
      in the community. A second study demonstrated that the provision of plasma BNP
      data improves the speed of diagnosis and reduces the rates of hospital admission
      and length of hospital stay (while reducing the costs of care) in patients with
      heart failure who are seen the emergency department with acute dyspnea. Finally,
      a randomized controlled pilot study demonstrated that serial measurements of NT
      proBNP can be used to more effectively optimize heart failure pharmacotherapy
      with a concomitant improvement in outcome. CONCLUSION: The large body of
      observational data, coupled with this small but promising evidence base from
      controlled trials (which attests to beneficial effects on clinical outcomes)
      encourages an optimistic outlook for the further implementation of plasma BNP
      and/or NT-proBNP in the diagnosis and treatment of acute and chronic heart
      failure.

PMID- 15948099
TI  - NT-ProBNP in acute heart failure: correlation with invasively measured
      hemodynamic parameters during recompensation.
AB  - BACKGROUND: N-terminal brain natriuretic peptide (NT-proBNP) level is elevated in
      patients with acute and chronic heart failure. This study addresses whether NT
      proBNP correlates with invasively measured hemodynamic parameters and whether a
      decrease of NT-proBNP over time correlates with invasively monitored hemodynamic
      improvement. METHODS AND RESULTS: Twenty consecutive patients with acute
      exacerbation of chronic heart failure (New York Heart Association class III-IV)
      were included in this prospective study. NT-proBNP and hemodynamic measurements
      by balloon-tipped pulmonary artery catheter were performed simultaneously.
      Recompensation strategies included vasodilators, diuretics, and inotropes. The
      patients were divided in 2 subgroups. Group A, by definition, had a hemodynamic
      improvement over 24 hours with an increase of cardiac index of >30% and a
      decrease of pulmonary capillary wedge pressure of >30%. Group B did not show a
      hemodynamic improvement. Group A had a decline of NT-proBNP levels to 42% of the
      baseline value over 32 hours. In group B, the NT-pro BNP levels did not change
      significantly over 32 hours. CONCLUSION: The decrease of NT-proBNP correlates
      with hemodynamic improvement in patients with decompensated heart failure. The
      relative changes of NT-proBNP seem to be a reliable diagnostic tool in monitoring
      these patients. There results have been confirmed in a larger patient group.

PMID- 15948100
TI  - Improvement of serum NT-ProBNP predicts improvement in cardiac function and
      favorable prognosis after cardiac resynchronization therapy for heart failure.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is now an established therapy
      for patients with advanced heart failure with electromechanical delay, although
      nonresponders have been observed. Because natriuretic peptides are relevant
      markers to reflect the severity of heart failure and filling pressure of cardiac
      chambers, it may be helpful to assess the efficacy of CRT. METHODS AND RESULTS:
      Forty-two patients with heart failure with QRS of >120 msec were recruited; their
      serial N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured
      at baseline and at 1 and 3 months after CRT. There was a reduction in NT-proBNP
      level 1 month after CRT (2655 +/- 2242 pg/mL vs 2149 +/- 2033 pg/mL; P = .03),
      which was further reduced at 3 months (1473 +/- 1786 pg/mL; P < .001 vs
      baseline). The reduction of NT-proBNP correlated with the change of left
      ventricular (LV) end-systolic volume (r = 0.53; P = .001) or LV ejection fraction
      ( r = -0.49; P = .002) and with improvement in exercise capacity after CRT for 3
      months (r = 0.50; P = .002). The patients were classified by the degree of
      reduction in NT-proBNP as group 1 (reduction of > or =50% vs baseline; n = 19)
      and group 2 (reduction of <50% vs baseline; n = 23). The degree of LV reverse
      remodeling (-31.8 +/- 24.7 mL vs -12.6 +/- 19.2 mL; P = .007) and gain in LV
      ejection fraction (+12.5% +/- 8.8% vs +4.6% +/- 5.8%; P = .002) were
      significantly better in group 1 than group 2. Both the all-cause mortality rate
      (Log-rank chi 2 = 4.01; P = .04) and the composite end-point of mortality rate or
      hospitalization rate for cardiovascular causes (Log-rank chi 2 = 4.31; P = .02)
      were significantly lower in group 1 than in group 2. CONCLUSION: Serial
      monitoring of NT-proBNP may be helpful to predict a favorable outcome after CRT.
      Those who had a reduction of NT-proBNP level of >/=50% were more likely to
      exhibit a favorable response.

PMID- 15948101
TI  - N-terminal brain natriuretic peptide, but not anemia, is a powerful predictor of
      mortality in advanced heart failure.
AB  - BACKGROUND: Anemia is prevalent in patients with chronic heart failure, the
      proportion of which increases with deteriorating New York Heart Association
      functional class. Anemia is also associated with increased symptoms, more
      frequent hospitalizations, and, in some studies, with an increased mortality
      rate. We have demonstrated that N-terminal brain natriuretic peptide (NT-proBNP)
      is a powerful predictor of death in advanced heart failure and is superior to the
      traditional markers of chronic heart failure (CHF) severity. However, to date,
      there are no published data that compare the prognostic ability of NT-proBNP with
      that of hemoglobin and hematocrit in patients with advanced heart failure who are
      referred for consideration of cardiac transplantation at a time when
      erythropoietin is under investigation as a treatment option in such a population.
      METHODS AND RESULTS: We prospectively studied 182 consecutive patients with
      advanced CHF who had been referred for consideration of cardiac transplantation.
      Blood samples were taken at recruitment for routine investigation and for NT
      proBNP analysis; the patients' condition was followed for a median of 554 days.
      The primary end point of all-cause death was reached in 30 patients, and the
      secondary end point of all-cause death or urgent cardiac transplantation was
      reached in 34 patients. The mean hemoglobin level was 13.9 +/- 2.2 g/dL, and the
      median concentration of NT-proBNP was 1505 pg/mL (interquartile range, 517-4015).
      The only multivariate predictor of all-cause death (chi 2 = 14.2; P < .001) or
      the secondary end point of all-cause death or urgent transplantation (chi 2 =
      21.8; P < .001) was an NT-proBNP concentration above the median value.
      CONCLUSION: A single measurement of NT-proBNP in patients with advanced CHF can
      help to identify patients who are at a higher risk of death and is a better
      prognostic marker than anemia.

PMID- 15948102
TI  - NT-ProBNP in non-ST-elevation acute coronary syndrome.
AB  - BACKGROUND: The role of N-terminal pro-brain natriuretic peptide (NT-proBNP) in
      the early treatment of patients with non-ST-elevation acute coronary syndrome
      (NSTACS) has been evaluated in 6 large studies that include >12,000 patients.
      METHODS AND RESULTS: These studies convincingly show that this marker of cardiac
      performance is associated strongly with death and the risk of future congestive
      heart failure and carry important prognostic information that is independent from
      previous known risk factors in NSTACS. As such, NT-proBNP can be added to
      existing risk stratification models and multimarker approaches. There is some
      data that indicate that this marker might also be helpful in guiding decisions
      about coronary revascularization in these patients, but further studies are
      needed. CONCLUSION: Before routine use of NT-proBNP in NSTACS, the extra cost of
      adding this new marker to the current routine markers and its impact on selection
      of treatment should be considered.

PMID- 15948103
TI  - Can exercise-induced changes in B-type natriuretic peptides be used to detect
      cardiac ischemia?
AB  - BACKGROUND: We reviewed the current medical literature that pertained to the
      question of whether myocardial ischemia triggers the release of B-type
      natriuretic peptides (BNPs) and, in particular, whether transient exercise
      induced ischemia can be detected by the measurement of changes in these
      biomarkers. BNPs are well-established as markers of left ventricular dysfunction,
      particularly heart failure. There is accumulating evidence that various
      conditions with the common denominator of myocardial ischemia are also associated
      with increased circulating levels of these peptides. METHODS AND RESULTS:
      Recently published methods and results, which includes our published and
      unpublished data, were reviewed. CONCLUSION: The results show that exercise
      induced ischemia or its associated regional wall-motion abnormalities trigger the
      release of BNPs and that the measurement of plasma levels of N-terminal pro brain
      natriuretic peptide and BNP before and immediately after symptom-limited exercise
      can distinguish patients with and without ischemia with a high degree of
      accuracy.

PMID- 15948104
TI  - N-terminal pro-brain natriuretic peptide as an indicator of right ventricular
      dysfunction.
AB  - BACKGROUND: Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain
      natriuretic peptide (BNP) are elevated in most patients with acute pulmonary
      embolism (APE) that results in right ventricular overload. Therefore, APE should
      be considered in the differential diagnosis of patients with acute dyspnea and
      abnormal levels of BNPs. Moreover, plasma BNPs have been proved to predict
      outcome in APE. METHODS AND RESULTS: Low NT-proBNP or BNP levels characterize an
      uneventful hospital course, and NT-proBNP levels of <500 pg/mL identify patients
      who could potentially be candidates for care on a complete outpatient basis.
      Moreover, plasma NT-proBNP and BNP reflect the degree of right ventricular
      overload in APE. Plasma BNPs can also be elevated in chronic precapillary
      pulmonary hypertension and are strongly related to total pulmonary resistance.
      Elevated plasma levels of BNP/NT-proBNP and especially their further increase
      during follow-up are a potent predictor of poor survival. CONCLUSION: Because
      levels of brain natriuretic peptides are elevated significantly not only in
      pathologic conditions that affect the left ventricle but also in clinical
      conditions that lead to isolated acute or chronic right ventricular overload, it
      could be proposed that these peptides should not be regarded as biomarkers of
      congestive heart failure, but as indicators of cardiovascular dyspnea.

PMID- 15948105
TI  - N-terminal pro-brain natriuretic peptide in arterial hypertension: a valuable
      prognostic marker of cardiovascular events.
AB  - BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) provides
      important prognostic information in patients with chronic heart failure and in
      the general population. The aim of this study was to evaluate NT-proBNP as a
      prognostic marker of cardiovascular morbidity and death in a sample of subjects
      with hypertension and preserved left ventricular systolic function from the
      general population. METHODS AND RESULTS: The study population was recruited from
      4 general practitioners. The study participants (n = 569 subjects; ages, 50-89
      years) completed a heart failure questionnaire and were submitted to blood
      pressure measurement, electrocardiography, echocardiography, and blood sampling.
      After exclusion of subjects with left ventricular ejection fraction of <50%, 270
      subjects fulfilled the following criteria for hypertension: history of
      hypertension or blood pressure >150/90 mmHg. During 3 years of follow-up, 28
      subjects (10.4%) reached the composite end point of death, stroke/transient
      ischemic attack, or myocardial infarction. After adjustment for cardiovascular
      risk factors, NT-proBNP (logarithmically transformed) independently predicted the
      risk of experiencing a composite end point (hazard ratio, 1.94; P < .0001), and
      death (hazard ratio, 2.28; P < .0001). The risk of having a composite end point
      (21 vs 7; P = .005) was significantly higher for subjects with NT-proBNP above
      the study median than for subjects with NT-proBNP below the study median.
      CONCLUSION: In this sample of subjects with hypertension and preserved left
      ventricular systolic function from the general population, plasma NT-proBNP was
      found to be a valuable cardiovascular risk marker, independently of traditional
      risk factors and prevalent cardiovascular disease.

PMID- 15948106
TI  - Clinical value of NT-ProBNP and BNP in pediatric cardiology.
AB  - BACKGROUND: Although less common than in adults, heart disease is a significant
      cause for morbidity and death in infants and children. Congenital structural
      cardiac anomalies and acquired heart diseases may result in heart failure.
      METHODS AND RESULTS: Available data suggest that the natriuretic peptide system
      has a similar role in health and disease in the pediatric age group as in adults.
      In healthy infants and children, levels of B-type natriuretic peptide (BNP) and
      the N-terminal segment of its pro-hormone (NT-proBNP) are elevated in the first
      few days after birth. Thereafter, their levels decrease and remain relatively
      constant throughout childhood. Infants and children with heart disease that
      causes significant pressure or volume overload of the right or the left ventricle
      have elevated BNP and NT-proBNP levels. In children with congestive heart
      failure, BNP and NT-proBNP levels correlate with functional capacity. Both
      peptides can differentiate cardiac from pulmonary causes in infants with
      respiratory distress. Limited data suggest that these peptides may also serve as
      markers in cyanotic, obstructive, and inflammatory heart diseases. CONCLUSION:
      The present data suggest that both NT-proBNP and BNP are markers for heart
      disease in infants and children. Their use may improve clinical practice in
      pediatric cardiology.

PMID- 15948107
TI  - NT-ProBNP: the mechanism behind the marker.
AB  - Brain natriuretic peptide (BNP) was isolated originally from porcine brain
      extracts but was soon defined as a cardiac natriuretic hormone. Together with the
      highly homologous atrial natriuretic peptide, it forms a dual natriuretic peptide
      system of the heart. The main stimulus for proBNP synthesis and secretion from
      cardiac myocytes is myocyte stretch. On secretion, the propeptide is split into
      the biologically active BNP and the remaining part of the prohormone N-terminal
      proBNP (NT-proBNP). In heart failure increased wall stretch, neurohormonal
      activation and hypoxia stimulate BNP secretion. The recently demonstrated
      production of BNP by stimulated cardiac fibroblasts is of uncertain
      pathophysiologic importance. In contrast to atrial natriuretic peptide, BNP is a
      constitutively secreted hormone with relatively little intracellular storage of
      mature peptide. In the normal state, the atrium is the main cardiac production
      site, but as heart failure develops, there is a profound activation of
      ventricular NT-proBNP synthesis. BNP acts on distant tissues and causes diuresis,
      vasodilatation, and decreased renin and aldosterone secretion. Known mechanisms
      of BNP clearance from plasma include binding to the natriuretic peptide clearance
      receptor type-C and proteolysis by peptidase NEP 24.11. NT-proBNP has a longer
      half-life and thus higher plasma concentration than BNP. It probably is cleared
      from plasma by renal excretion and possibly other unknown pathways.

PMID- 15948108
TI  - Elecsys NT-ProBNP and BNP assays: are there analytically and clinically relevant
      differences?
AB  - BACKGROUND: B-type natriuretic peptide (BNP; 77-108 amino acids) and its N
      terminal (1-76 amino acids) counterpart, NT-proBNP, are cardiac biomarkers that
      have been established for the assessment of left ventricular dysfunction and
      congestive heart failure and provide prognostic and risk stratification
      information for patients with acute coronary syndrome. Various automated
      immunoassays currently are available for the measurement of these natriuretic
      peptides, but there are significant analytical differences, especially between
      BNP and NT-proBNP. METHODS AND RESULTS: Recently published methods and results
      were reviewed. CONCLUSION: Although there are significant pre-analytical and
      analytical differences between the Triage BNP and Elecsys NT-proBNP and other BNP
      methods, they do not translate to clinically significant differences in their
      diagnostic and prognostic application in the assessment of systolic heart failure
      and risk stratification of patients with acute coronary syndrome. However, there
      appears to be some evidence that suggests that NT-proBNP may have an advantage in
      the detection of patients with mild or asymptomatic heart disease.

PMID- 15948109
TI  - Do we need two more mesothelial markers?

PMID- 15948111
TI  - Dr William DeMonbreun: description of his contributions to our understanding of
      histoplasmosis and analysis of the significance of his work.
AB  - Histoplasmosis was proven to be a fungal infection 70 years ago by Dr William
      DeMonbreun, at the time an assistant professor in the Department of Pathology at
      Vanderbilt Medical School. The significance of his work is analyzed in
      relationship to the evolution of knowledge about this important fungal infection.
      His discovery was also central to establishing the legitimacy of the recently
      reorganized medical school. Vanderbilt Medical School in 1925 was an experiment
      in building an educational institution essentially from scratch-the outcome of
      the experiment could be judged in the near term only by research productivity and
      Dr DeMonbreun's work was one of the 5 major discoveries made at Vanderbilt in the
      first decade of its existence. Further, his work is the bedrock on which Christie
      and Peterson later showed that histoplasmosis was endemic in the Ohio River
      Valley. Their studies plus a host of case reports and reviews up to recent times
      have contributed significantly to the academic standing of Vanderbilt. Heretofore
      unpublished illustrations and details about the prototypic cases are included for
      historical purposes. New light is also shed on the chain of circumstances that
      led to Vanderbilt's role in the evolution of knowledge about histoplasmosis.
      Finally, information is provided about Dr DeMonbreun's career after his
      discovery.

PMID- 15948112
TI  - Mesothelioma with clear cell features: an ultrastructural and immunohistochemical
      study of 20 cases.
AB  - Mesotheliomas with clear cell morphology are rare and only a few individual case
      reports have been documented in the literature. The author reports a series of 20
      epithelioid mesotheliomas with clear features, 17 of which originated in the
      pleura and 3 in the peritoneum. Eighteen of the patients were men and 2 were
      women. Twelve patients had a history of asbestos exposure. Electron microscopy
      and special histochemical stains demonstrated that the cytoplasmic clearing seen
      in hematoxylin and eosin-stained sections resulted from multiple factors that can
      occur either singly or in combination. The most frequent cause of the cytoplasmic
      clearing was the accumulation of large amounts of intracytoplasmic glycogen.
      Another but somewhat less common factor was the accumulation of large amounts of
      lipid, which occurred alone or with glycogen. Other less common causes were
      marked mitochondrial swelling, the presence of numerous intracytoplasmic
      vesicles, and a large number of intracytoplasmic lumens. The value of
      immunohistochemistry in helping to distinguish epithelioid mesotheliomas from
      some carcinomas with clear cell morphology is emphasized. In addition, it was
      determined that because electron microscopy was decisive in establishing the
      cause of the cytoplasmic clearing in most of the cases, tissue for electron
      microscopy should routinely be procured for ultrastructural studies.

PMID- 15948113
TI  - Stromal elastosis in papillary thyroid carcinomas.
AB  - Stromal elastosis, defined as dense aggregations of elastic fibers, is found in
      some neoplastic tissues especially in malignant tumors of the breast and lung.
      Although also found in thyroid tissue, stromal elastosis in thyroid neoplasms
      have received little attention. To clarify the histopathological significance of
      stromal elastosis in the thyroid, we examined neoplastic (n = 223) and
      hyperplastic (n = 82) thyroid tissues in conjunction with cancer tissues (n =
      193) of various other organs. Stromal elastosis was observed as deposits of pale
      homogeneous material in hematoxylin and eosin stain, and distinctively
      highlighted by elastic-van Gieson's stain. On immunohistochemical examination,
      elastin and tropoelastin were confirmed in these deposits. Stromal elastosis was
      found in 66% of papillary thyroid carcinomas (PTCs), although it was not
      identified in other histological types of thyroid neoplasms. In PTCs, deposits of
      elastic fibers varied in size and shape, and were more frequently distributed in
      the periphery of the tumor tissue. The histological subtypes of PTC varied in
      prevalence of elastosis with the follicular variant's (9%) prevalence being
      significantly lower than that of the classical type (72%). The frequency of
      stromal elastosis in PTCs was very similar to the frequencies in breast and lung
      adenocarcinomas, and higher than the frequencies in carcinomas of other organs.
      In conclusion, our results suggest that stromal elastosis is a characteristic
      histological finding of PTCs, presumably associated with their growth pattern
      and/or histological architecture. It is, therefore, reasonable to propose that
      stromal elastosis is an ancillary feature in the histopathological diagnosis of
      PTCs.

PMID- 15948114
TI  - Basal cell hyperplasia: an unusual diagnostic dilemma on prostate needle
      biopsies.
AB  - Basal cell hyperplasia (BCH) is a well-recognized entity on transurethral
      resection specimens, but it is an uncommon finding on prostatic needle biopsies,
      and the diagnostic difficulties with it have not been fully defined on this
      material. A 13-year (1991-2003) retrospective review of the consult files of one
      of the authors was performed. In all cases, the focus of BCH was referred for
      consultation to rule out adenocarcinoma. Thirty-three cases of prominent BCH were
      identified. The dominant pattern of BCH consisted of either glands (26/33) or
      solid nests (7/33). Other minor patterns included cribriform (5),
      pseudocribriform (4), cords (1), and adenoid basal (1). Twelve of 33 cases showed
      an infiltrative pattern. Other features of BCH included prominent nucleoli
      (14/33), abnormal secretions (17/33 with dense pink and/or blue mucin), mitoses
      (6/33), altered stroma with increased cellularity (6/33), calcifications (6/33),
      intraluminal crystalloids (3/33) and perineural invasion (1/33). By
      immunohistochemistry, 7 (100%) out of 7 were positive for p63 and 14 (88%) of 16
      were positive for high molecular weight cytokeratin. No cases (0/6) were positive
      for alpha-methylacyl-coenzyme A racemase. Basal cell hyperplasia, as a mimicker
      of cancer, is an uncommon entity encountered on prostatic needle biopsies.
      Helpful features for its diagnosis include solid nests, pseudocribriform glands,
      multilayering of cells, calcifications, and cellular stroma. Immunohistochemistry
      can be useful for documenting the basal cell layer and demonstrating negative
      racemase staining.

PMID- 15948115
TI  - Human malignant melanoma: detection of BRAF- and c-kit-activating mutations by
      high-resolution amplicon melting analysis.
AB  - Activating mutations in the BRAF kinase have been reported in a large number of
      cases of malignant melanoma. This suggests that therapy with specific RAF kinase
      inhibitors may find use in treating this disease. If the response to RAF kinase
      inhibition is dependent on the presence of an activated BRAF protein, it will be
      necessary to evaluate cases of malignant melanoma for the presence or absence of
      BRAF mutations. High-resolution amplicon melting analysis is able to detect
      single base-pair changes in DNA isolated from paraffin-embedded tissue sections
      and obviates the need for direct DNA sequencing. Results can be available within
      48 hours. In this report, we used high-resolution amplicon melting analysis to
      evaluate 90 cases of malignant melanoma for BRAF mutations. Of these 90 cases, 74
      were metastatic melanomas, 12 were primary cutaneous melanomas, and 4 were in
      situ melanomas. BRAF activation mutations were found in 43 cases (48%). Forty-one
      of these mutations were in exon 15. The mutations in exon 15 included V600E (34
      cases), V600K (6 cases), and V600R (1 case). Two activating mutations were found
      in exon 11, G469V and G469R. The presence or absence of a BRAF mutation in the
      junctional component of an invasive melanoma was maintained in the invasive
      component. We also evaluated these 90 cases, as well as an additional 10 cases
      (total of 100) for the expression of c-kit. The majority of invasive and
      metastatic malignant melanomas did not express c-kit, although all in situ
      lesions and the junctional components of invasive lesions were strongly c-kit
      positive. Surprisingly, 2 cases of metastatic malignant melanoma (2%) showed
      strong and diffuse c-kit expression and contained a c-kit-activating mutation,
      L576P, as detected by high-resolution amplicon melting analysis and confirmed by
      direct DNA sequencing. These 2 c-kit mutation-positive cases did not contain BRAF
      mutations. The presence of a c-kit-activating mutation in metastatic malignant
      melanoma suggests that a small number of melanomas may progress by a somatic
      mutation of the c-kit gene. The presence of BRAF- and c-kit-activating mutations
      in malignant melanoma suggests new approaches to treating this disease involving
      specific tyrosine kinase inhibitors may prove worthwhile and that mutation
      analysis by high-resolution melting analysis might help guide therapy.

PMID- 15948116
TI  - Differential gene expression in anaplastic lymphoma kinase-positive and
      anaplastic lymphoma kinase-negative anaplastic large cell lymphomas.
AB  - Anaplastic large cell lymphoma (ALCL) is an aggressive large T- or null-cell
      lymphoma. Most ALCLs arising in children and young adults express a
      constitutively active receptor tyrosine kinase, anaplastic lymphoma kinase (ALK).
      Anaplastic large cell lymphomas lacking ALK are clinically heterogeneous and
      their pathogenesis is unknown. This study is the first complementary DNA (cDNA)
      microarray analysis using RNA extracted from tumor tissue (7 ALK+ ALCLs and 7 ALK
      ALCLs) to identify genes differentially expressed or shared between the ALK+ and
      ALK- tumors. Unsupervised hierarchical clustering using the top 11 most
      statistically significant discriminator cDNAs correctly grouped all ALK+ and ALK-
      tumors. Hierarchical clustering analysis using the 44 cDNAs with the greatest
      differential expression between ALK+ and ALK- RNAs grouped 6 of 7 ALK+ ALCLs
      together and 1 ALK+ ALCL with the ALK- group. In general, ALK+ tumors overexpress
      genes encoding signal transduction molecules (SYK , LYN , CDC37) and underexpress
      transcription factor genes (including HOXC6 and HOX A3 ) compared with the ALK-
      group. Cyclin D3 was overexpressed in the ALK+ group and the cell cycle inhibitor
      p19INK4D was decreased in the ALK- group, suggesting different mechanisms of
      promoting G 1 /S transition. Both groups had similar proliferation rates. Genes
      highly expressed in both ALK- and ALK+ ALCLs included kinases (LCK, protein
      kinase C, vav2, and NKIAMRE) and antiapoptotic molecules, suggesting possible
      common pathogenetic mechanisms as well.

PMID- 15948117
TI  - A review of 55 cases of cutaneous lymphoid hyperplasia: reassessment of the
      histopathologic findings leading to reclassification of 4 lesions as cutaneous
      marginal zone lymphoma and 19 as pseudolymphomatous folliculitis.
AB  - To clarify the confusion surrounding the diagnosis of cutaneous lymphoid
      hyperplasia (CLH) that was formerly described as lymphadenosis benigna cutis,
      lymphocytoma cutis, or lymphocytic infiltration of Jessner and to assess whether
      newly recognized diagnoses, such as cutaneous marginal zone lymphoma and
      pseudolymphomatous folliculitis (PLF), may have been overlooked, we reexamined 55
      Japanese cases of nonepidermotropic lymphoproliferative disorder that had
      previously been diagnosed as "cutaneous pseudolymphoma." In all these cases, the
      immunohistochemical expressions of CD1a, CD3, CD4, CD8, CD20, CD21, CD30, CD43,
      CD56, CD68, CD79a, kappa and lambda chains, S-100 protein, and latent membrane
      protein were assessed. In addition, in 13 cases the gene rearrangement of the
      immunoglobulin heavy chain was investigated using a polymerase chain reaction
      method. As a result of these investigations, we have identified 4 cases of
      cutaneous marginal zone lymphoma, 19 cases of PLF, 1 case of diffuse large B-cell
      lymphoma, and 2 cases of solitary nonepidermotropic pseudo-T-cell lymphoma, with
      the remaining 29 cases being CLH. Cutaneous marginal zone lymphoma, which
      represented 7.3% of the total, was distinguished from CLH by the presence of
      patchy or diffuse proliferation of centrocyte-like cells, plasma cells at the
      periphery of the lymphocytic infiltration, monotypic restriction of the light
      chains, and gene rearrangement of the immunoglobulin heavy chain.
      Pseudolymphomatous folliculitis was identified by the presence of activated
      pilosebaceous units with abundant CD1a-and S-100 protein-positive T-cell
      activated dendritic cells. Of the cases that were reassessed, 34.5% were PLF.

PMID- 15948118
TI  - Identification of germ cells at risk for neoplastic transformation in
      gonadoblastoma: an immunohistochemical study for OCT3/4 and TSPY.
AB  - Carcinoma in situ (CIS) is the precursor of malignant testicular germ cell tumors
      (GCTs) of adolescents and young adults, being the neoplastic counterpart of
      primordial germ cells/gonocytes. Carcinoma in situ cells will develop into
      invasive seminoma/nonseminoma. Gonadoblastoma (GB) is the precursor of invasive
      GCTs in dysgenetic gonads, predominantly dysgerminoma (DG). In this process, part
      of the Y chromosome (GBY region) is involved, for which TSPY is a candidate gene.
      A detailed immunohistochemical survey was performed for the known diagnostic
      markers, germ cell/placental alkaline phosphatase (PLAP), c-KIT, and OCT3/4, as
      well as testis-specific protein on the Y chromosome (TSPY) on a series of GBs,
      and adjacent invasive DGs. All 5 patients were XY individuals (4 females and 1
      male). In contrast to c-KIT, PLAP was positive in all cases. The immature germ
      cells of GBs were positive for OCT3/4, whereas the mature germ cells were
      negative for this marker, but positive for TSPY. In every GB, a minor population
      of germ cells positive for both markers could be identified, similar to most CIS
      cells and early invasive DG. On progression to an invasive tumor, TSPY can be
      lost, a process that is also detectable in invasive testicular GCTs compared to
      CIS. These results indicate that GB is a heterogeneous mix of germ cells, in
      which the OCT3/4-positive cells have the potential to undergo progression to an
      invasive tumor. These early invasive stages are initially also positive for TSPY
      (like CIS), supporting a positive selection mechanism. Therefore, OCT3/4 in
      combination with TSPY is valuable to identify malignant germ cells in dysgenetic
      gonads. This could allow better prediction of the risk of progression to a GCT.
      In addition, the data support the model that GB represents the earliest
      accessible developmental stage of malignant GCTs.

PMID- 15948119
TI  - Overexpression of laminin-5 gamma2 chain and its prognostic significance in
      urothelial carcinoma of urinary bladder: association with expression of
      cyclooxygenase 2, epidermal growth factor receptor [corrected] and human
      epidermal growth factor receptor [corrected] 2.
AB  - Laminin-5 (LN-5) and cyclooxygenase 2 (COX-2) play important roles in many kinds
      of cancers. Recently, it has been reported that epidermal growth factor receptor
      [corrected] (EGFR) and/or human epidermal growth factor receptor [corrected] 2
      (HER2) expressions are associated with LN-5 and/or COX-2 expressions in a few
      carcinoma cell lines and human tumor tissue. LN-5, COX-2, EGFR, and HER2
      expressions were examined immunohistochemically in 67 patients with urothelial
      carcinomas (UCs), and associations among these 4 biomarkers and clinicopathologic
      characteristics were investigated. Patients were classified into transurethral
      resection group and cystectomy group based on clinical end points, and prognostic
      significances of increased expressions were evaluated. Overexpression of LN-5,
      COX-2, EGFR, and HER2 was observed in 16 (23.9%), 34 (50.7%), 42 (62.7%), and 15
      (22.4%) of 67 patients, respectively. LN-5 overexpression was associated high
      grade (P = .002), invasive (pTa+1 versus pT2-4, P = .011), and nonpapillary (P =
      .027) UCs. Concerning EGFR and HER2, high-grade (EGFR, P = .0009; HER2, P = .003)
      and nonpapillary (EGFR, P = .016; HER2, P = .0002) UCs had a significantly higher
      overexpression rate. UCs penetrating basal membrane (pT1-4) showed significantly
      higher overexpression rates than pTa UCs on all biomarkers. In transurethral
      resection group, LN-5 overexpression could be proved as an independent prognostic
      parameter for intravesical recurrence (P = .007), whereas in cystectomy group,
      nodal involvement was an independent prognostic parameter for cause-specific
      survival (P = .025). The current study showed that the 4 biomarkers were
      associated with aggressive behaviors of UCs. Above all, LN-5 overexpression was
      considered to play an important role in intravesical recurrence of superficial
      UCs.

PMID- 15948120
TI  - The utility of Ki-67 expression in the differential diagnosis of prostatic
      intraepithelial neoplasia and ductal adenocarcinoma.
AB  - Cribriform and/or papillary prostatic lesions observed on limited tissue, such as
      needle biopsy, can pose diagnostic dilemmas. One such area of difficulty is the
      distinction between papillary and/or cribriform prostatic high-grade prostatic
      intraepithelial neoplasia (HG-PIN) and ductal adenocarcinoma. Over 48 months, we
      identified 17 cases of ductal adenocarcinoma and 17 cases of HG-PIN from radical
      retropubic prostatectomy specimens. The HG-PIN lesions were in all cases
      associated with an acinar prostatic adenocarcinoma component. For each case, we
      evaluated the proliferative activity, assessed by Ki-67 immunohistochemistry. The
      majority (82%) of ductal adenocarcinomas were composed of mixed papillary and
      cribriform patterns, with the remaining demonstrating pure papillary or
      cribriform patterns. The HG-PIN lesions showed a papillary, cribriform, or mixed
      papillary/cribriform architecture. The proliferative activity, defined as Ki-67
      labeling index, was statistically higher in ductal adenocarcinoma (mean 33%,
      range 21%-66%) as compared with HG-PIN (mean 6%, range 2%-15%), with no overlap
      in the Ki-67 indices (P = 0001). A combination of histological features and
      measurements of cellular proliferation may be helpful to distinguish HG-PIN from
      ductal adenocarcinoma in limited prostatic tissue samples.

PMID- 15948121
TI  - The phosphorylated form of connexin43 is up-regulated in breast hyperplasias and
      carcinomas and in their neoformed capillaries.
AB  - We applied an antiserum (SA226P) specifically recognizing the phosphorylated form
      of connexin43 (P-Cx43) to human breast samples including normal breast samples,
      with fibrocystic disease (FCD), fibroadenomas (FA), in situ and infiltrating
      carcinomas of all major types, and miscellaneous extramammary tumors. The
      findings were compared with those obtained with commercial antisera recognizing
      all Cx43 forms (pan-Cx43). A subset of samples was stained for Her2-neu and
      p44/42 to mitogen-activated protein kinase. Paraffin step sections were used.
      Immunoblots were performed on frozen samples of a representative subset of cases.
      In the normal breast, FCD, and FA, SA226P stained strongly and extensively most
      myoepithelial cells (MECs); luminal cells remained unstained. In proliferative
      FCD and some cellular FA, SA226P stained MEC and the capillary endothelium (CE).
      In ductal and lobular in situ carcinomas, SA226P reacted strongly and diffusely
      with the remaining MEC, the CE, and the transformed luminal cells. SA226P stained
      all infiltrating carcinomas except the tubular variant. In all breast carcinomas,
      the CE within and adjacent to tumors and some myofibroblasts stained with SA226P.
      By contrast, pan-Cx43 stained weakly and sporadically the MEC and rare samples of
      invasive carcinomas. Notably, Mab p44/42 reacted in parallel with the samples
      stained with SA226P, whereas reactions with Her2 were negative. Immunoblot
      findings paralleled those obtained immunohistochemically. We conclude that P
      Cx43, restricted to MEC in the normal breast, is up-regulated in the same cells
      in hyperplasias and dysplasias and FA and is strongly up-regulated in invasive
      carcinomas. Notably, in some proliferative FCD and in most in situ and
      infiltrating carcinomas, P-Cx43 is strongly expressed in CE within and adjacent
      to the lesions but not away from them. These findings were paralleled by the
      strong nuclear reactions noted with Mab p44/42. These phenomena, although not
      exclusive to malignancy, are particularly conspicuous in breast carcinomas and
      seemingly reflect active proliferation associated with abnormal gap junctional
      intercellular communication.

PMID- 15948122
TI  - Inflammatory cells in the formation of tumor-related sarcoid reactions.
AB  - Tumor-related sarcoid reactions were analyzed in 14 lymph nodes in comparison
      with sarcoidosis using immunohistochemical markers to lymphocytes (CD3, CD4, CD8,
      and CD20), myeloid-related protein (MRP) 8 and MRP14 (S100A8 and S100A9),
      angiotensin I-converting enzyme (CD143), and mature or immature dendritic cells
      (S100, HLA-DR, fascin, CD83, and CD1a). We found that solitary epithelioid cell
      granuloma (ECG) first occur between lymph sinus and T-zone and that multiple ECGs
      mainly occur within T-zone, whereas confluent types often occupy the whole lymph
      node except some residual lymphoid follicles. This pattern suggests a continuous
      spread and growth of ECGs in sarcoid reactions along T-zone, where antigen
      presentation mainly takes place. Irrespective of granuloma type, a constant
      invasion of freshly recruited MRP8 + and MRP14 + macrophages was observed.
      Similar to sarcoidosis, angiotensin I-converting enzyme expression was a constant
      finding in epithelioid and giant cells, suggesting a common inflammatory pathway.
      An increasing ratio of CD4 + to CD8 + T lymphocytes (r = 0.789, P = .001) and a
      decreasing number of S100 + and CD83 + dendritic cells (r = 0.787, P = .001)
      within ECGs correlated with granuloma growth, whereas CD1a + immature dendritic
      cells were never observed inside ECGs. Our findings show that sarcoid reactions
      represent a T-cell-mediated immune response, leading to histological appearance
      and cell distribution similar to sarcoidosis and other granulomatous conditions,
      but the mechanism is different from dendritic cell-based tumor vaccination.
      Furthermore, mature dendritic cells occur inside ECGs especially of early sarcoid
      reactions but may not be required for the enlargement and further maintenance of
      ECGs, in contrast to CD4 + lymphocytes.

PMID- 15948123
TI  - Lack of PTEN expression in endometrial intraepithelial neoplasia is correlated
      with cancer progression.
AB  - We tested the hypothesis that PTEN inactivation may stratify cancer progression
      risk among putative endometrial hyperplasias, classified prognostically by means
      of the morphometric D score (DS). The DS, calculated from 3 morphometric
      variables measured in routine hematoxylin-eosin-stained endometrial biopsy
      slides, is the most sensitive and specific method of endometrial cancer risk
      prediction currently available. Clinical outcomes of 103 women with endometrial
      hyperplasia on biopsy were tallied according to the DS. Seven (7/103; 7%)
      patients with carcinoma during follow-up were all distributed within the high
      risk prognostic group (ie, DS <1 = endometrial intraepithelial neoplasia [EIN])
      (7/21; 33% progression). None of the 82 cases with a DS higher than 1 progressed.
      All cases that progressed were PTEN null, indicating that this genotype is
      capable of further stratifying cancer progression risk in hyperplasias
      irrespective of histological categorization. However, only 16% of the PTEN-null
      cases progressed. When PTEN expression pattern was combined with EIN, the
      prognostic power was greatly increased (specificity from 63% for PTEN and 85% for
      EIN to 93% when combined; positive predictive value from 16% and 33% to 50%). We
      conclude that loss of PTEN expression is the first biomarker in EIN that
      increases the accuracy of the prognostic DS to predict cancer progression risk.
      Unless endometrial hyperplasias are stratified by histological morphometric D
      Score, PTEN has a low positive predictive value.

PMID- 15948124
TI  - Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma.
AB  - Neuroendocrine (NE) tumor cells in prostatic carcinoma (PCa) may influence tumor
      proliferation by a paracrine stimulus. The role of NE tumor cells is discussed
      controversially. This study investigates the influence of NE tumor
      differentiation on proliferation in PCa. Neuroendocrine differentiation, Ki-67,
      and Polo-like kinase 1 were studied immunohistochemically in 73 consecutive
      prostatectomies. Polo-like kinase 1 (PLK1) expression was also studied by Western
      and Northern blot analysis. Tumors were classified as high NE (HNE) and low NE
      differentiated (LNE), and depending on the growth pattern, with solitary and
      clusters of NE tumor cells. Low NE differentiated tumors were defined as less
      than 30 and HNE as 30 or more NE tumor cells per hot spot. Patients were followed
      by serum prostate-specific antigen (PSA) analysis. Neuroendocrine differentiation
      was present at least focally in 70% of tumors; 57% were HNE and 43% LNE. Solitary
      NE tumor cells were more often found in low-grade PCa, whereas clusters of NE
      tumor cells were more frequent in high-grade PCa. PLK1 messenger RNA and protein
      as well as Ki-67 were overexpressed in tumor tissue compared with tumor-free
      tissue. A stronger proliferation as determined by Ki-67 and PLK1 expression was
      present in HNE tumors compared with LNE tumors and in tumors with clusters in
      contrast to tumors with solitary NE tumor cells. Analysis for PSA relapse-free
      survival showed an earlier progression in HNE than in LNE tumors and in PCa with
      clusters of NE tumor cells. A significant and clustered NE differentiation in PCa
      may lead to an increased proliferation and earlier tumor progression, whereas few
      and solitary NE tumor cells have no prognostic impact.

PMID- 15948125
TI  - Transformation of follicular lymphoma to Burkitt-like lymphoma within a single
      lymph node.
AB  - Aberrant expression of bcl-2 , caused by a t(14;18) translocation, is most
      commonly associated with follicular lymphoma. In a subset of these tumors,
      additional acquisition of a translocation involving c-myc leads to transformation
      to a high-grade lymphoma. We report a case of follicular lymphoma containing a
      t(14;18) translocation transforming into a Burkitt-like lymphoma containing the
      original t(14;18) as well as an additional t(8;14). The latter translocation
      resulted in the phenotype of Burkitt-like lymphoma, and the transformation from
      follicular lymphoma to Burkitt-like lymphoma was demonstrable within a single
      lymph node. To the best of our knowledge, this is the first report of a case
      documenting direct transformation of follicular lymphoma into Burkitt-like
      lymphoma in the same lymph node. This case illustrates the dramatic oncogenic
      stimulus that results from the inhibition of apoptosis by bcl-2 combined with the
      deregulation of cell growth by c-myc .

PMID- 15948126
TI  - Autoimmune enteric leiomyositis: a rare cause of chronic intestinal pseudo
      obstruction with specific morphological features.
AB  - Autoimmune enteric leiomyositis is an extraordinary rare cause of acquired
      chronic intestinal pseudo-obstruction in children. We report a 5-year-old girl
      who developed chronic intestinal pseudo-obstruction 3 years after an autoimmune
      hepatitis. Mucosal biopsies of the upper gastrointestinal tract and colon showed
      minimal inflammatory changes. On full-thickness biopsies of the small intestine,
      a dense lymphocytic infiltrate of the muscularis propria was seen, mainly
      consisting of cytotoxic T lymphocytes. Smooth muscle fibers were degenerated and
      diminished, but the myenteric plexus was intact. The coexistence of an autoimmune
      hepatitis in our case indicates an expansion of autoreactive T cells to
      homologous self-antigens. It is of practical importance for histopathological
      diagnosis that inflammation in autoimmune enteric leiomyositis affects the
      muscularis propria of the small intestine, whereas mucosa and submucosa do not
      show severe inflammatory changes. Therefore, correct diagnosis may be missed in
      peroral and peranal mucosal biopsies, but full-thickness biopsies are required.

PMID- 15948127
TI  - Placental site trophoblastic tumor of the mediastinum.
AB  - Choriocarcinoma has been described as the most frequent subtype of mediastinal
      germ cell tumors showing trophoblastic differentiation. We report a unique case
      of a placental site trophoblastic tumor, which developed in the mediastinum of a
      14-year-old boy 2 years after the resection of a mature teratoma. The recurrent
      tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically,
      diffusely infiltrating large polygonal cells with focal nodular growth and a
      teratomatous part containing mature intestinal, respiratory, and squamous
      epithelium with adjacent cutaneous adnexal structures were found. The typical
      morphologic features included vessel wall infiltration by the neoplastic cells
      with fibrinoid deposits and geographic necroses within the tumor masses.
      Characteristic diffuse positivity for melanoma cell adhesion molecule and human
      leucocyte antigen G was found on immunohistochemical investigation, confirming
      the diagnosis of placental site trophoblastic tumor. The patient died 1 year
      later after polychemotherapy. The outcome of this rare tumor is similar to the
      reported poor clinical outcome in patients with mediastinal choriocarcinomas.

PMID- 15948128
TI  - Hypereosinophilia with systemic thrombophlebitis.
AB  - A 34-year-old Japanese woman developed subcutaneous induration in the left thigh,
      then showed extreme eosinophilia, and died of hemorrhagic infarction of the
      brain. Autopsy revealed endocarditis with eosinophil infiltration and systemic
      thrombophlebitis, including pulmonary veins and intrahepatic branches of the
      portal vein. Arterial structure was relatively preserved. She had no clinical
      history of asthma and had anti-ascarid IgE antibody at postmortem serological
      examination; thus, her disease does not fulfill the diagnostic criteria of Churg
      Strauss syndrome and idiopathic hypereosinophilic syndrome (HES). Her organ
      involvement is, however, consistent with that of HES; thus, her
      pathophysiological conditions would resemble those of HES. Systemic
      thrombophlebitis without arterial lesion in patients with hypereosinophilia has
      never been reported, and this case would broaden the spectrum of vascular lesions
      in these patients.

PMID- 15948129
TI  - A stem cell role for thyroid solid cell nests.

PMID- 15948130
TI  - Thinking "out of the nest"--a reply to "a stem-cell role for thyroid solid cell
      nests [letter]".

PMID- 15948131
TI  - Eosinophilic myocarditis and fibrosis.

PMID- 15948132
TI  - A molecular recognition paradigm: promiscuity associated with the ligand-receptor
      interactions of the activin members of the TGF-beta superfamily.
AB  - The structure-function properties of the pleiotropic activins and their
      relationship to other members of the transforming growth factor-beta superfamily
      of proteins are described. In order to highlight the molecular promiscuity of
      these growth factors, emphasis has been placed on molecular features associated
      with the recognition by activin A and the bone morphogenic proteins of the
      corresponding extracellular domains of the ActRI and ActRII receptors. The
      available evidence suggests that the homodimeric activin A in its various
      functional roles has the propensity to fulfill key tasks in the regulation of
      mammalian cell behaviour, through coordination of numerous transcriptional and
      translational processes. Because of these profound effects, under physiologically
      normal conditions, activin A levels are closely controlled by a variety of
      binding partners, such as follistatin-288 and follistatin-315, alpha(2)
      macroglobulin and other proteins. Moreover, the subunits of other members of the
      activin subfamily, such as activin B or activin C, are able to form heterodimers
      with the activin A subunit, thus providing a further avenue to positively or
      negatively control the physiological concentrations of activin A that are
      available for interaction with specific receptors and induction of cell signaling
      events. Based on data from X-ray crystallographic studies and homology modeling
      experiments, the molecular architecture of the ternary receptor-activin ligand
      complexes has been dissected, permitting rationalization in structural terms of
      the pattern of interactions that are the hallmark of this protein family.

PMID- 15948133
TI  - Association of a CAV-1 haplotype to familial aggressive prostate cancer.
AB  - BACKGROUND: Multiple lines of evidence have implicated the CAV-1 gene in prostate
      cancer progression. CAV-1 is located within the prostate cancer aggressiveness
      locus at 7q31-33, and was identified as being overexpressed in prostate tumors.
      Mutation screening was performed as well as a case-control study to examine if
      polymorphisms in CAV-1 are associated with prostate cancer aggressiveness in a
      German population. METHODS: We sequenced the CAV-1 promoter region and its open
      reading frame in prostate cancer families with linkage to chromosome 7q31-33.
      Additionally, 105 unrelated familial prostate cancer probands, 190 sporadic
      cases, and 191 controls were genotyped at four intronic single nucleotide
      polymorphisms. Resulting haplotypes were tested for association using age at
      diagnosis, tumor grade, TNM stage, and follow up information to stratify for
      aggressive disease. RESULTS: No mutation was found in the CAV-1 coding region or
      in the promoter. One of the 11 observed haplotypes showed an increased frequency
      in cases with high tumor stage (P = 0.03). CONCLUSIONS: This is the first report
      providing evidence for CAV-1 being involved in predisposition to aggressive
      prostate cancer. The association of a potential risk haplotype agrees well with a
      role of CAV-1 in tumor progression but needs further confirmation.

PMID- 15948134
TI  - A role for surfactant protein D in innate immunity of the human prostate.
AB  - OBJECTIVES: Surfactant protein D (SP-D) is a member of the collectin family of
      proteins, which are involved in host defense mechanisms in the lung. In the
      present study, we found that SP-D is produced in the human prostate where it may
      play a role in innate immunity. METHODS AND RESULTS: Using reverse-transcriptase
      PCR and Western blot analysis, we demonstrate that SP-D mRNA and protein are
      present in human prostate tissue. In situ hybridization and immunohistochemistry
      revealed that SP-D mRNA and protein are localized in epithelial cells of prostate
      glands. Prostate glands that are surrounded by inflammatory cells produce
      increased amounts of SP-D protein. We also show that SP-D inhibits the infection
      of LNCaP and P69SV40T prostate epithelial cells by Chlamydia trachomatis in an in
      vitro infection assay. Furthermore, using truncated human SP-D mutants, we
      demonstrate that SP-D binds to Chlamydia trachomatis via its carboxy-terminal
      lectin domains. CONCLUSIONS: Our in vitro studies suggest that SP-D protects the
      prostate from infection by pathogens. SP-D protein levels are increased at sites
      of inflammation in the prostate, suggesting SP-D may also contribute more
      generally to inflammatory regulation in the prostate.

PMID- 15948135
TI  - Patupilone (epothilone B, EPO906) inhibits growth and metastasis of experimental
      prostate tumors in vivo.
AB  - BACKGROUND: Microtubule agents appear promising for the treatment of prostate
      cancer. Patupilone (epothilone B), a highly potent non-taxane microtubule
      stabilizing agent, was evaluated in models of androgen-independent prostate
      cancer. METHODS: Patupilone was administered to athymic mice bearing human
      prostate cancer xenografts (subcutaneous DU 145 and PC-3M, orthotopic PC-3M).
      RESULTS: One 4 mg/kg patupilone administration produced transient regression of
      DU 145 tumors, while two weekly administrations of 2.5 mg/kg produced stable
      disease followed by protracted regression, however with more pronounced body
      weight loss. Taxol (15 mg/kg every other day) weakly inhibited tumor growth, but
      with less body weight loss. Patupilone (5 mg/kg) produced protracted growth
      inhibition of subcutaneous PC-3M tumors, with transient body weight loss. In mice
      with orthotopic PC-3M tumors, 4 or 5 mg/kg/week patupilone impaired primary tumor
      growth, abrogated metastases and enhanced survival, with only transient body
      weight loss. CONCLUSIONS: These data suggest that patupilone holds promise for
      prostate cancer treatment.

PMID- 15948136
TI  - Lymphatic vessel density and lymph node metastasis in prostate cancer.
AB  - BACKGROUND: Few data are available examining the significance of prostatic
      lymphatic vessel density (LVD) to lymph node metastasis in patients with prostate
      cancer. The purpose of this study was to determine the distribution of lymphatic
      vessels in non-carcinomatous prostate tissue, and investigate the relationship
      between LVD and lymph node status in prostate cancer. METHODS: LVD, identified by
      D2-40 immunostaining, was evaluated in non-carcinomatous prostates (n = 7) and
      prostate cancer (n = 37). The staining pattern of D2-40 was compared with that of
      another lymphatic vessel marker, vascular endothelial growth factor (VEGF)
      receptor-3, and a blood vessel endothelial marker, CD34, in adjacent sections.
      RESULTS: The D2-40 antigen, podoplanin, was expressed exclusively in lymphatic
      vessels within tumor and normal tissue in all specimens. There was no overlap
      between cell staining for D2-40 and CD34. Peritumoral LVD and peritumoral
      lymphatic invasion were significantly associated with lymph node metastasis. VEGF
      receptor-3 was expressed in a subset of D2-40+ lymphatic vessels. CONCLUSIONS: We
      have demonstrated that peritumoral lymphatic vessels are likely to serve as major
      conduits for nodal metastasis in prostate cancer using D2-40 to decorate
      lymphatic endothelium marker podoplanin. Lack of coexpression of podoplanin and
      VEGF receptor-3 in some lymphatic vessels suggests the heterogeneity of lymphatic
      endothelial cells in prostate tissue.

PMID- 15948137
TI  - Assessment of intra-individual variation in prostate-specific antigen levels in a
      biennial randomized prostate cancer screening program in Sweden.
AB  - BACKGROUND: The degree of variability in prostate-specific antigen (PSA)
      measurements is important for interpreting test results in screening programs,
      and particularly for interpreting the significance of changes between repeated
      tests. This study aimed to determine the long-term intra-individual variation for
      PSA in healthy men. METHODS: A randomly selected cohort of men in a biennial
      prostate cancer screening program (ERSPC) conducted in Sweden from 1995-1996 to
      2001-2002. We studied men who had total PSA (tPSA) levels < 2.0 ng/ml in 2001
      2002. This included 791 men with tPSA < or = 0.61 ng/ml (group A), 1,542 men with
      tPSA < or = 0.99 ng/ml (group B), and 1,029 men with tPSA 1.00-1.99 ng/ml (group
      C). The intra-individual variability of free PSA (fPSA) and tPSA was assessed by
      calculating coefficients of variation (CV) for each individual's PSA measurements
      from the first and second round of screening (1995-1996 and 1997-1998). RESULTS:
      Intra-individual CV (geometric means) for tPSA were 13.7%, 12.7%, and 11.5% in
      groups A, B, and C, respectively. Corresponding CVs for fPSA were significantly
      lower, ranging from 12.1% to 10.4%. The estimated biological variation of tPSA
      and fPSA in groups A to C were 12.5%, 11.4%, 10.0% and 9.7%, 7.8%, 7.5%,
      respectively. CONCLUSIONS: In healthy men with PSA levels less than 2 ng/ml, the
      natural long-term variability for tPSA was less than 14%, and with 95%
      probability, a change in tPSA greater than 30% indicates a change beyond normal
      random variation.

PMID- 15948138
TI  - Dual inhibition of the epidermal growth factor and vascular endothelial growth
      factor phosphorylation for antivascular therapy of human prostate cancer in the
      prostate of nude mice.
AB  - BACKGROUND: Androgen-independent prostate cancer (PCa) may be susceptible to
      modulation of the tumor microenvironment. We determined whether a dual tyrosine
      kinase inhibitor (AEE788) of the epidermal growth factor receptor (EGF-R) and
      vascular endothelial growth factor receptor (VEGF-R) combined with chemotherapy
      can produce therapy of human PCa in nude mice. METHODS: PC-3MM2 human PCa cells
      were injected into the prostate of nude mice. Three days later, the mice were
      randomized into four groups: saline control, paclitaxel, AEE788, and AEE788 and
      paclitaxel. The mice were treated for 5 weeks and necropsied. Tumor incidence,
      weight, and incidence of lymph node metastasis were recorded. Tumor tissue was
      analyzed immunohistochemically. RESULTS: Treatment of mice with AEE788 or AEE788
      plus paclitaxel significantly decreased tumor incidence, total tumor weight, and
      incidence of lymph node metastasis. AEE788 treatment alone or in combination with
      paclitaxel inhibited the phosphorylation of EGF-R and VEGF-R on tumor cells and
      tumor-associated endothelial cells. Therapeutic efficacy correlated with an
      increase in apoptosis of tumor cells and tumor-associated endothelial cells.
      CONCLUSION: Blockade of EGF-R and VEGF-R signaling pathways coupled with
      chemotherapy suppressed the progressive growth and metastasis of human PCa cells
      growing orthotopically in nude mice.

PMID- 15948139
TI  - Protamine: a unique and potent inhibitor of oligopeptidase B.
AB  - Oligopeptidase B is a serine endopeptidase found in prokaryotes, unicellular
      eukaryotes and higher plants. The enzyme has been shown recently to play a
      central role in the pathogenesis of several parasitic diseases such as African
      trypanosomiasis, and to be a potential therapeutic target. This study reports
      that protamine, a basic peptide rich in arginine, is a potent inhibitor at the
      nanomolar level of oligopeptidase B from E. coli and wheat. Protamines 1B, 2C, 3A
      and TP17 displayed similar inhibitory activities and were capable of binding
      strongly to oligopeptidase B without proteolytic cleavage. The concentration of
      protamine needed for 50% inhibition (IC50) of oligopeptidase B was 10(4)-fold
      lower than the IC50 of trypsin. Oligopeptidase B was highly sensitive to
      inhibition by protamines even in the presence of serum (IC50, 1 microM). These
      data indicate that protamines might provide information useful for the design of
      more specific synthetic oligopeptidase B inhibitors.

PMID- 15948141
TI  - Synthesis and secondary structure in membranes of the Bcl-2 anti-apoptotic domain
      BH4.
AB  - Solid phase synthesis of BH4, the 26 amino-acid domain
      (6RTGYDNREIVMKYIHYKLSQRGYEWD31) of the anti-apoptotic Bcl-2 protein has been
      accomplished using Fmoc chemistry. The use of peculiar cleavage conditions
      provided high yields after purification such that tens to hundreds of mg could be
      obtained. A 15N-labelled version of the peptide could also be synthesized for NMR
      studies in membranes. The peptide purity was not lower than 98% as controlled by
      UV and MALDI-TOF mass spectrometry. The secondary structure was determined in
      water, trifluoroethanol (TFE) and in lipid membrane using UV circular dichroism.
      The peptide shows dominant beta-sheeted structures in water that convert
      progressively into alpha-helical features upon addition of TFE or membrane. The
      amphipathic character of the helix suggests that the peptide might have a
      structure akin to those of antimicrobial peptides upon interaction with
      membranes.

PMID- 15948140
TI  - Dynamic localization and persistent stimulation of factor-dependent cells by a
      stem cell factor / cellulose binding domain fusion protein.
AB  - The extracellular matrix provides structural components that support the
      development of tissue morphology and the distribution of growth factors that
      modulate the overall cellular response to those growth factors. The ability to
      manipulate the presentation of factors in culture systems should provide an
      additional degree of control in regulating the stimulation of factor-dependent
      cells for tissue engineering applications. Cellulose binding domain (CBD) fusion
      protein technology facilitates the binding of bioactive cytokines to cellulose
      materials, and has permitted the analysis of several aspects of cell stimulation
      by surface-localized growth factors. We previously reported the synthesis and
      initial characterization of a fusion protein comprised of a CBD and murine stem
      cell factor (SCF) (Doheny et al. [1999] Biochem J 339:429-434). A significant
      advantage of the CBD fusion protein system is that it permits the stimulation of
      factor-dependent cells with localized growth factor, essentially free of
      nonfactor-derived interactions between the cell and matrix. In this work, the
      long-term stability and bioactivity of SCF-CBD fusions adsorbed to
      microcrystalline cellulose under cell culture conditions is demonstrated.
      Cellulose-bound SCF-CBD is shown to stimulate receptor polarization in the cell
      membrane and adherence to the cellulose matrix. In addition, cellulose-surface
      presentation of the SCF-CBD attenuates c-kit dephosphorylation kinetics,
      potentially modulating the overall response of the cell to the SCF signal.

PMID- 15948142
TI  - Conformational analysis of human calcitonin in solution.
AB  - The solution conformation of human calcitonin in a mixture of 60% water and 40%
      trifluoroethanol has been determined by the combined use of 1H NMR spectroscopy
      and distance geometry calculations with a distributed computing technique. 1H NMR
      spectroscopy provided 195 distance constraints and 13 hydrogen bond constraints.
      The 20 best converged structures exhibit atomic rmsd of 0.43 A for the backbone
      atoms from the averaged coordinate position in the region of Asn3-Phe22. The
      conformation is characterized by a nearly amphiphilic alpha-helix domain that
      extends from Leu4 in the cyclic region to His20. There are no significant
      differences observed among the overall structures of a series of calcitonins
      obtained from ultimobranchial bodies, including those that possess 20- to 50-fold
      greater activity. Three aromatic amino acid residues, Tyr12, Phe16 and Phe19,
      form a hydrophobic surface of human calcitonin. Bulky side chains on the surface
      could interfere with the ligand-receptor interaction thereby causing its low
      activity, relative to those of other species.

PMID- 15948143
TI  - Synthesis of a novel conformationally restricted Val-Phe dipeptidomimetic.
AB  - A method for the synthesis of (3(R,S),6S,11b(R,S))-1,3,4,6,7,11b-hexahydro-4-oxo
      3-phthalimidopyrido[2,1-a]isoquinoline-6-carboxylic acid 2 as a new
      conformationally restricted dipeptidomimetic of Val-Phe is reported. It involved
      cyclisation via an intramolecular electrophilic addition at the reactive
      bridgehead carbon. This new scaffold can be used as a building block in the
      preparation of libraries of peptidomimetics.

PMID- 15948144
TI  - Critical influence of Eschscholzia californica cells nutritional state on
      secondary metabolite production.
AB  - In this study, we investigated the influence of initial internal nutrient
      concentrations at the time of elicitation on the ability of Eschscholzia
      californica (EC) cells to produce alkaloids. Three EC cell suspensions cultivated
      in culture media differing in their PO4(3-) and NO3- contents were sampled daily
      for 12 days and analyzed for extracellular and intracellular nutrient
      concentrations. The ability of the cells to produce alkaloids was tested along
      the three cell suspension cultures. Sampled cells were then further cultured for
      7 days in a production medium containing the elicitor and an extraction resin.
      The alkaloid production of the cells was measured 7 days post-elicitation. In the
      low-N medium, starch, glucose, and phosphate contents in the biomass was
      increased by 470, 1624 and 70%, respectively, 10 days after inoculation compared
      to the control culture in standard B5 medium. Cell concentration was
      significantly reduced from 10.3 to 8.6 millions cell/mL on this low-N medium
      compared to the control, nevertheless alkaloid production was multiplied by 39 at
      day 10 when cells were elicited. Cells grown on the low-N or low-P media
      accumulated 83% and 188% more carbon, respectively, than control cells at the end
      of the culture. This intracellular C was mainly stored in the form of starch in
      low-P medium and both in the form of starch and glucose in the low-N medium. The
      ability of EC cells to produce alkaloids upon elicitation was shown to be
      strongly dependent on the initial intracellular C and P content at the time of
      elicitation. This suggests that reproducibility and productivity during EC cell
      culture could be enhanced by manipulating the intracellular C and P content at
      the time of elicitation.

PMID- 15948145
TI  - Beneficial effect of silkworm hemolymph on a CHO cell system: Inhibition of
      apoptosis and increase of EPO production.
AB  - To produce erythropoietin (EPO), Chinese hamster ovary (CHO) cells were first
      cultured in a medium containing FBS (growth medium) and then in a serum-free
      medium containing sodium butyrate (production medium). Sodium butyrate increases
      recombinant protein production, but also induces apoptosis, which reduces cell
      viability and productivity. In a previous study, we found that silkworm hemolymph
      (SH), an insect serum, inhibits the apoptosis of insect and mammalian cells. To
      overcome sodium butyrate-induced apoptosis, we added SH to growth medium. This
      pretreatment with SH inhibited the sodium butyrate-induced apoptosis of CHO cells
      and consequently increased their longevity and their ability to produce EPO. As a
      result, the volumetric productivity of EPO was increased five-fold. SH was found
      to inhibit cytochrome c release from mitochondria into the cytosol, and prevented
      the activation of caspase-3 and other subsequent caspase reactions.

PMID- 15948147
TI  - Human Gas7 isoforms homologous to mouse transcripts differentially induce neurite
      outgrowth.
AB  - Gas7, a growth-arrest-specific protein, is expressed preferentially in the brain
      and is required for neurite outgrowth in cultured cerebellar and peripheral
      murine neurons. Gas7 interacts with F-actin and colocalizes with the terminal
      part of actin microfilament in cells in which membrane outgrowth is present. Gas7
      isoforms were discovered in murine brain by alternative splicing. This work
      reports the identification of two human Gas7 cDNA: hGas7-a with 2,427
      nucleotides, which encodes 330 amino acids, and hGas7-b with 2,610 nucleotides,
      which encodes 412 amino acids according to predicted open-reading-frames. The
      predicted hGas7-b protein is 97% homologous to murine homologues, whereas the
      hGas7-a is homologous to the mouse Gas7-cb form that is expressed preferentially
      in cerebellum. Alignment analysis of the Gas7 protein sequences revealed a high
      homology to that in humans: 99% for the monkey, 97% in murine, and around 75% for
      the puffer fish and chicken. The hGas7-b protein comprises a WW domain, which
      often associates with other domains that are typically present in proteins in
      signal transduction processes, and an FCH domain, which participates in
      rearranging the cytoskeleton. The hGas7-a comprises only the FCH domain. Analysis
      of the human Gas7 sequences using the DNA database revealed that the two forms
      resulted from the canonical alternative splicing of a Gas7 genomic sequence. The
      abundance of both hGas7 mRNA levels, determined by quantitative PCR in tissues
      including brain, breast cancer, placenta, and head-neck cancer, revealed that the
      level of hGas7-a was 14 times that of hGas7-b in these tissues. Transfection of
      cells with hGas7-a or hGas7-b cDNA yielded the predicted 38-kDa or 50-kDa
      protein, respectively. The ectopic expression of hGas7 caused neurite-like cell
      processes in both mouse Neuro-2a and human SH-SY5Y neuroblastoma cells.
      Interestingly, the hGas7-a preferentially elicited the small lamellipodia,
      whereas the hGas7-b elicited the small filopodia phenotype. These findings reveal
      the evolutionary conservation of the structure and function of Gas7. They also
      suggest that the FCH domain in Gas7 may participate in the development of
      lamellipodia, and the WW domain may participate in the fine-tuning of the
      filopodia.

PMID- 15948146
TI  - Modulation of glioma BK channels via erbB2.
AB  - Glioma cells show up-regulation and constitutive activation of erbB2, and its
      expression correlates positively with increased malignancy. A similar correlation
      has been demonstrated for the expression of gBK, a calcium-sensitive, large
      conductance K(+) channel. We show here that glioma BK channels are a downstream
      target of erbB2/neuregulin signaling. Tyrphostin AG825 was able to disrupt the
      constituitive erbB2 activation in a dose-dependent manner, causing a 30-mV
      positive shift in gBK channel activation in cell-attached patches. Conversely,
      maximal stimulation of erbB2 with a recombinant neuregulin (NRG-1beta) caused a
      12-mV shift in the opposite direction. RT-PCR studies reveal no change in the BK
      splice variants expressed in treated glioma cells. Furthermore, isolation of
      surface proteins through biotinylation did not show a change in gBK channel
      expression, and probing with phospho-specific antibodies showed no alteration in
      channel phosphorylation. However, fura-II Ca(2+) fluorescence imaging revealed a
      35% decrease in the free intracellular Ca(2+) concentration after erbB2
      inhibition and an increase in NRG-1beta-treated cells, suggesting that the
      observed changes most likely were due to alterations in [Ca(2+)](i). Consistent
      with this conclusion, neither tyrphostin AG825 nor NRG-1beta was able to modulate
      gBK channels under inside-out or whole-cell recording conditions when
      intracellular Ca(2+) was fixed. Thus, gBK channels are a downstream target for
      the abundantly expressed neuregulin-1 receptor erbB2 in glioma cells. However,
      unlike the case in other systems, this modulation appears to occur via changes in
      [Ca(2+)](i) without changes in channel expression or phosphorylation. The
      enhanced sensitivity of gBK channels in glioma cells to small, physiological
      Ca(2+) changes appears to be a prerequisite for this modulation.

PMID- 15948148
TI  - Manganese transport by rat brain endothelial (RBE4) cell-based transwell model in
      the presence of astrocyte conditioned media.
AB  - Manganese (Mn), an essential nutrient, is neurotoxic at high levels and has been
      associated with the development of a parkinsonian syndrome termed manganism.
      Currently, the mechanisms responsible for transporting Mn across the blood-brain
      barrier (BBB) are unknown. By using rat brain endothelial 4 (RBE4) cell
      monolayers cultured in astrocyte-conditioned media (ACM), we examine the effects
      of temperature, energy, proton (pH), iron (Fe), and sodium (Na(+)) dependence on
      Mn transport. Our results suggest that Mn transport is temperature, energy, and
      pH dependent, but not Fe or Na(+) dependent. These data suggest that Mn transport
      across the BBB is an active process, but they also demonstrate that the presence
      of ACM in endothelial cell cultures decreases the permeability of these cells to
      Mn, reinforcing the use of ACM or astrocyte cocultures in studies examining metal
      transport across the BBB.

PMID- 15948149
TI  - Familial association of prostate cancer with other cancers in the Swedish Family
      Cancer Database.
AB  - BACKGROUND: Familial associations between cancer sites may implicate true
      familial clustering which is relevant for the identification of new cancer
      syndromes and for clinical counseling. METHODS: We used the nation-wide Swedish
      Family-Cancer Database, containing 10,553 sons and 107,518 fathers with prostate
      cancer among a total of 170,000 cancer patients in the 0- to 70-year-old
      offspring generation and over 800,000 cancer patients in the parental generation.
      We calculated familial standardized incidence ratios (SIRs) and confidence
      intervals (CIs) for prostate cancers and other cancers in family members.
      RESULTS: SIRs for prostate cancer were increased in sons when mothers were
      diagnosed with breast and ovarian cancers, and when siblings were diagnosed with
      Hodgkins disease (1.78, N = 18, 95% CI 1.05-2.82) and leukemia (1.39, 43, 1.01
      1.88). Liver cancer and melanoma were also in excess in the high-risk families.
      CONCLUSIONS: The present analysis, the largest yet carried out, found many novel
      associations implying familial links between prostate cancer and other sites.

PMID- 15948150
TI  - Effect of GnRH analogs on the expression of TrkA and p75 neurotrophin receptors
      in primary cell cultures from human prostate adenocarcinoma.
AB  - BACKGROUND: GnRH analogs have antiproliferative and/or apoptotic effects on
      prostate cancer cells. Also, neurotrophin receptors TrkA and p75 have been
      reported in normal prostate suggesting a role in the gland growth control. In
      prostate cancer, TrkA receptors seem to be overexpressed and p75 receptors show a
      decreased expression. These changes in neurotrophin receptors may be related with
      unbalanced growth in malignant cells. In the present study we investigate the
      effects of GnRH analogs (leuprolide and cetrorelix) on the expression of TrkA and
      p75 neurotrophin receptors in primary cultures of human prostate cancer cells.
      METHODS: Tissue was obtained from radical prostatectomies due to prostate
      adenocarcinoma. Cells were isolated after sequential enzyme digestion and
      cultured in defined media. Nerve growth factor (NGF) receptors in untreated
      cultures were estimated by immunofluorescence. Cultures were treated with
      leuprolide (agonist) or cetrorelix (antagonist) and expression of TrkA and p75
      receptors were evaluated by semi quantitative RT-PCR (polymerase chain reaction)
      and western blot. Cell proliferation was estimated by MTT method and apoptosis
      through COMET assay. RESULTS: Both leuprolide and cetrorelix induced a
      significant increase in p75 receptor gene and protein expression at a
      concentration that induce apoptosis and decrease proliferation. TrkA receptors
      showed no changes in presence of GnRH analogs. CONCLUSIONS: GnRH analogs,
      leuprolide, and cetrorelix, change the ratio between neurotrophin receptors TrkA
      and p75 by increasing gene and protein expression of p75 receptor. Considering
      that TrkA receptor is related with proliferation and p75 with apoptosis, we
      suggest that our findings may explain, in part, the effect of GnRH analogs on
      prostate cancer growth.

PMID- 15948151
TI  - Magnetic resonance imaging of the axial skeleton enables objective measurement of
      tumor response on prostate cancer bone metastases.
AB  - BACKGROUND: There is currently no technique to image quantitatively bone
      metastases. Here, we assessed the value of MRI of the axial skeleton (AS-MRI) as
      a single step technique to quantify bone metastases and measure tumor response.
      METHODS: AS-MRI was performed in 38 patients before receiving chemotherapy for
      metastatic HRPCa, in addition to PSA, computed tomography of the thorax, abdomen,
      and pelvis [CT-TAP]; and Tc-99m bone scintigraphy. A second AS-MRI was performed
      in 20 patients who completed 6 months of chemotherapy. Evaluation of tumor
      response was performed using RECIST. RESULTS: Only 11 patients (29%) had RECIST
      measurable metastases in soft-tissues or lymph nodes on baseline CT-TAP. AS-MRI
      identified a diffuse infiltration of the bone marrow in 8 patients and focal
      measurable metastatic lesions in 25 patients (65%), therefore, doubling the
      proportion of patients with measurable lesions. Transposing RECIST on AS-MRI in
      20 patients who completed 6 months of treatment, allows the accurate estimation
      of complete response (n = 2), partial response (n = 2), stable disease (n = 5),
      or tumor progression (n = 11), as it is done using CT-TAP in soft tissue solid
      metastases. CONCLUSIONS: MRI of axial skeleton enables precise measurement and
      follow-up of bone metastases as it is for other soft-tissue metastasis.

PMID- 15948152
TI  - Phosphatidic acid and diacylglycerol generation is regulated by insulin in
      cerebral cortex synaptosomes from adult and aged rats.
AB  - Insulin receptor associated with the cerebral cortex (CC) has been shown to be
      involved in brain cognitive functions. Furthermore, deterioration of insulin
      signaling has been associated with age-related brain degeneration. We have
      reported previously that aging stimulates phospholipase D/phosphatidate
      phosphohydrolase 2 (PLD/PAP2) pathway in CC synaptosomes from aged rats,
      generating a differential availability of their reaction products: diacylglycerol
      (DAG) and phosphatidic acid (PA). The aim of this work was to determine the
      effect of aging on DAG kinase (DAGK), as an alternative pathway for PA
      generation, and to evaluate the effect of insulin on PLD/PAP2 pathway and DAGK.
      PLD, PAP2, and DAGK activities were measured using specific radiolabeled
      substrates in CC synaptosomes from adult (4 months old) and aged rats (28 months
      old). In adult animals, in the presence of the tyrosine phosphatase inhibitor
      (sodium o-vanadate), insulin stimulated PLD activity at 5 min incubation. DAGK
      activity was also increased at the same time of incubation and PAP2 was
      inhibited. In aged animals, PLD activity was not modified by the presence of
      insulin plus vanadate, PAP2 was inhibited, and DAGK was stimulated by the
      hormone. Insulin, vanadate, and the combination of both induced protein tyrosine
      phosphorylation in adult CC synaptosomes. Aged rats showed a lower level of
      protein phosphorylation with respect to adult rats. Our results show that insulin
      modulates PA and DAG availability through the regulation of PLD/PAP2 and DAGK
      pathways in adult rat CC synaptosomes. Additionally, we demonstrated that PA and
      DAG generation is regulated differentially by insulin during aging.

PMID- 15948154
TI  - Detachment and emission of airborne bacteria in gas-phase biofilm reactors.
AB  - Three laboratory scale biofilters filled with different packing materials (peat
      and sieved sugarcane bagasse) and operating with different microbial cultures
      (allochthonous and autochthonous bacteria) were run and monitored in parallel to
      assess the emission rate of airborne bacteria in the biofiltration of benzene
      contaminated air streams. The effect of the fluid dynamic and loading conditions
      on the rate of microbial emission in the air environment was investigated by
      performing continuous experiments at different inlet benzene concentrations and
      superficial gas velocities. The experiments prove that the concentration of
      airborne bacteria in the effluent air from lab-scale biofilters is only slightly
      higher than in the ambient air. The emission rate is not dependent on superficial
      gas velocity because of low shear stress exerted by the gas flow. On the other
      hand, the loading conditions have a strong effect on the emission rate, which
      increases with increasing growth and degradation rate, and different packing
      media show remarkably different behaviors.

PMID- 15948153
TI  - Differential effects of acute and subchronic administration on phencyclidine
      induced neurodegeneration in the perinatal rat.
AB  - Acute and subchronic administration of N-methyl-D-aspartate antagonists to rats
      in the early postnatal period has been reported to produce widespread and
      selectively cortical neurotoxicity, respectively. To resolve this apparent
      discrepancy, we sought to clarify these data by determining the dose and temporal
      and regional characteristics of acute and subchronic phencyclidine (PCP)-induced
      neurotoxicity. Measurement of degenerating neurons with the cupric silver
      technique following a single dose of PCP on postnatal day (PN) 7 revealed that
      neurodegeneration increased in all areas measured (frontal, parietal and
      cingulate cortices, striatum, hippocampus, subiculum, and thalamus) within 9 hr.
      Silver staining peaked at 9-16 hr and was then not detectable or was greatly
      reduced after 24 hr depending on the specific region. Dose-response analysis at 9
      hr showed that the lowest effective dose was 1, 3, and 10 mg/kg for the frontal
      cortex, hippocampus, and striatum, respectively. However, repeated PCP
      administration (10 mg/kg) on PN 7, 9, and 11 elicited an increase in silver
      staining only in the frontal cortex. To determine whether the loss of effect in
      the striatum and hippocampus was due to a "tolerance" mechanism or to a
      developmental phenomenon, we compared the effects of PCP given on PN 7, 9, or 11
      with those of two doses given on PN 7 and 9 or three doses administered on PN 7,
      9, and 11. Analysis of these experiments shows that both developmental factors
      and unknown mechanisms of tolerance underlie the apparent selective cortical
      neurotoxicity observed following subchronic PCP administration in perinatal rat
      pups.

PMID- 15948155
TI  - Suppression of Stat3 promotes neurogenesis in cultured neural stem cells.
AB  - To investigate the effects of signal transducer and activator of transcription 3
      (Stat3) on neural stem cell fate, stem cells were inoculated with an adenovirus
      vector expressing dominant negative form of Stat3 (Stat3F). One day later, a
      promoter assay revealed significant reduction of the transcriptional level in the
      transfected cells. Three days later, Western blot analysis and immunocytochemical
      analysis revealed that the protein level of microtubule-associated protein (MAP)2
      and the number of MAP2-positive cells were increased significantly in the
      transfected cells whereas the protein level of glial fibrillary acidic protein
      (GFAP) and the number of GFAP-positive cells were decreased significantly. In
      addition, mRNA levels of Notch family members (Notch1, 2, and 3) and of
      inhibitory basic helix-loop-helix (bHLH) factors (Hes5, Id2, and Id3) were
      significantly downregulated at 3 days after viral inoculation with Stat3F;
      however, mRNA levels of bHLH determination factors (Math1 and Neurogenin3) and
      bHLH differentiation factors (NeuroD1 and NeuroD2) were significantly
      upregulated. These data indicated that suppression of Stat3 directly induced
      neurogenesis and inhibited astrogliogenesis in neural stem cells.

PMID- 15948156
TI  - Changes in neuronal protein 22 expression and cytoskeletal association in the
      alcohol-dependent and withdrawn rat brain.
AB  - The action of alcohol on neuronal pathways has been an issue of increasing
      research focus, with numerous findings contradicting the previously accepted idea
      that its effect is nonspecific. The human NP22 (hNP22) gene was revealed by its
      elevated expression in the frontal cortex of the human alcoholic. The sequences
      of hNP22 and the rat orthologue rNP22 contain a number of domains consistent with
      those of cytoskeletal-interacting proteins. Localization of rNP22 is restricted
      to the cytoplasm and processes of neurons and it colocalizes with elements of the
      microfilament and microtubule matrices including filamentous actin (F-actin),
      alpha-tubulin, tau, and microtubule-associated protein 2 (MAP2). Withdrawal of
      Wistar rats after alcohol dependence induced by alcohol vapor produced elevated
      levels of rNP22 mRNA and protein in the cortex, CA2, and dentate gyrus regions of
      the hippocampus. In contrast, there was decreased rNP22 expression in the
      striatum after chronic ethanol exposure. Chronic ethanol exposure did not
      markedly alter rNP22 colocalization with F-actin, alpha-tubulin, or MAP2,
      although colocalization at the periphery of the neuronal soma with F-actin was
      observed only after chronic ethanol exposure and withdrawal. Rat NP22
      colocalization with MAP2 was reduced during withdrawal, whereas association with
      alpha-tubulin and actin was maintained. These findings suggest that the effect of
      chronic ethanol exposure and withdrawal on rNP22 expression is region selective.
      Rat NP22 may affect microtubule or microfilament function, thereby regulating the
      neuroplastic changes associated with the development of alcohol dependence and
      physical withdrawal.

PMID- 15948157
TI  - Methyl-4-phenylpyridinium ion modulates expression of mitochondrial uncoupling
      proteins 2, 4, and 5 in catecholaminergic (SK-N-SH) cells.
AB  - Methyl-4-phenylpyridinium ion (MPP(+)), a specific dopaminergic neurotoxin,
      inhibits mitochondrial complex I activity, generates reactive oxygen species
      (ROS), reduces ATP production, and induces cell death. We explored changes in
      expression of uncoupling proteins (UCPs 2, 4, and 5) following MPP(+)-induced
      toxicity in SK-N-SH cells over 72 hr at the transcriptional (quantification of
      mRNA by real-time RT-PCR) and translational (Western analysis) levels. UCP5 mRNA
      and protein were markedly up-regulated (1 mM MPP(+) at 72 hr caused a twofold
      increase, P < 0.01), as was UCP4 mRNA, albeit to a much lesser extent.
      Surprisingly, UCP2 mRNA levels decreased at 24 hr (P < 0.05) but thereafter
      significantly increased to greater than control levels at 72 hr (P < 0.05),
      although UCP2 protein levels were decreased throughout (1 mM MPP(+) at 72 hr
      caused a reduction of 50%, P < 0.01). The increase in ROS production may be
      attenuated by UCP4 and UCP5 up-regulation. The consequence of decreased UCP2
      levels is unclear, although this may represent an adaptive response to declines
      in ATP levels, the subsequent increase in mRNA being a response to further
      increases in oxidative stress.

PMID- 15948158
TI  - Immunosuppression and infectious complications in patients with stage IV indolent
      lymphoma treated with a fludarabine, mitoxantrone, and dexamethasone regimen.
AB  - BACKGROUND: Myelosuppression and immunosuppression occur with purine analogs. The
      objective of the current study was to investigate the effects of combined
      fludarabine, mitoxantrone, and dexamethasone (FND) followed by
      interferon/dexamethasone on myelosuppression (absolute neutrophil counts),
      immunosuppression (CD4 and CD8 counts), and infectious complications in patients
      with previously untreated, Stage IV indolent lymphoma. METHODS: Seventy-three
      patients were treated. All patients received Pneumocystis carinii pneumonia (PCP)
      prophylaxis. CD4 and CD8 counts, serum immunoglobulin (Ig) levels, and neutrophil
      counts were correlated with infectious complications. RESULTS: The median follow
      up was 6.1 years. Sixty of 73 patients had CD4, CD8, or Ig measurements. The
      median baseline CD4 count was 764/microL. This CD4 level decreased to 238/microL
      at 1 year and to 264/microL at 2 years; and it rose to 431/microL by 3 years and
      to 650/microL at 4 years. CD8 counts did not change significantly. The median
      baseline serum IgG level was 989 mg/d, decreased to 536 mg/dL at 1 year and to
      693 mg/dL at 2 years, and it rose to 949 mg/dL at 3 years and to 1080 mg/dL at 4
      years. Fourteen patients (19%) developed Grade 3-4 infections, the majority
      during FND therapy with neutropenia and/or accompanied by CD4 counts <
      200/microL. CD4, CD8, and neutrophil counts did not differ between patients who
      developed Grade 3-4 infections, Grade 1-2 infections, or no infections.
      CONCLUSIONS: Most infections with FND occurred during FND, in the setting of
      neutropenia, often with concurrent low CD4 counts. The overall safety profile for
      FND was good. However, patients should be monitored for opportunistic infections,
      and prophylactic antibiotics are recommended, particularly against PCP.

PMID- 15948159
TI  - Definitive surgery and multiagent systemic therapy for patients with localized
      Ewing sarcoma family of tumors: local outcome and prognostic factors.
AB  - BACKGROUND: The local management of Ewing sarcoma family of tumors (ESFT) often
      centers on the surgical resectability of the primary lesion and physician biases
      regarding differences in the morbidity between primary surgical and
      radiotherapeutic management. METHODS: The authors retrospectively reviewed the
      records of 33 patients with localized ESFT who underwent surgery and received
      systemic chemotherapy at St. Jude Children's Research Hospital (Memphis, TN). Two
      multiagent systemic chemotherapy regimens were used: 14 patients received
      vincristine, doxorubicin, cyclophosphamide, and actinomycin D (VACA), and 19
      received VACA in combination with ifosphamide and etoposide. The primary tumor
      was surgically resected via a wide, local excision (n = 32) or a marginal
      excision (n = 1)performed either at diagnosis or after 3-5 months of systemic
      chemotherapy. Clinical outcome and prognostic factors for disease control were
      reported in the current study. RESULTS: The median follow-up for patients was 9.9
      years. The 5-year and 10-year survival rates were 84.5% and 75.8%, respectively.
      At 5 years, the cumulative incidence of local disease recurrence was 12.5%, and
      the event-free survival (EFS) rate was 71.7%. The same values were found at 10
      years. The site of tumor origin was a significant predictor of EFS. The survival
      rate of patients whose tumors arose in bone was 78.6%, and the survival rate of
      patients whose tumors originated in soft tissue was 25.0% (P = 0.028). No other
      factors investigated were predictive of outcome. CONCLUSIONS: Local disease
      control and overall outcome for patients with ESFT managed by multiagent systemic
      therapy and surgery was excellent. Local disease control rates remained near 90%
      at 10-year follow-up. Patients with extraosseous primary sites of disease may
      fare less well with this approach to therapy.

PMID- 15948160
TI  - Influence of the time between surgery and radiotherapy on local recurrence in
      patients with lymph node-positive, early-stage, invasive breast carcinoma
      undergoing breast-conserving surgery: results of the French Adjuvant Study Group.
AB  - BACKGROUND: Radiotherapy (RT) after breast-conserving surgery (BCS) has produced
      significant reductions in ipsilateral breast carcinoma (BC) recurrence. It was
      shown previously that a delay in the initiation of RT resulted in a higher local
      recurrence (LR) rate. In the current retrospective analysis, the authors
      investigated whether the RT-adjuvant therapy sequence modified local-disease-free
      survival (L-DFS) after BCS in patients with early-stage, lymph node-positive BC.
      METHODS: Among 7 French Adjuvant Study Group trials, 1831 patients were
      assessable, including 475 patients who received RT directly after BCS (95
      patients received no adjuvant therapy, and 380 patients received hormone
      therapy), 567 patients who received RT after the third chemotherapy (CT) cycle
      (250 patients received 1-3 courses, and 317 patients received 4-6 courses), and
      789 patients received RT after the sixth CT cycle. In the 1356 patients who
      received CT, the regimens consisted of fluorouracil 500 mg/m(2); epirubicin 50
      mg/m(2), 75 mg/m(2), or 100 mg/m(2); and cyclophosphamide 500 mg/m(2) in 83.5% of
      patients. RESULTS: After a median follow-up of 102 months, 214 patients (11.7%)
      developed LR. The 9-year L-DFS rates were 92.0%, 81.5%, and 87.4%, respectively
      (P < 0.0001). It was worse in patients who received 1-3 CT cycles (P = 0.02).
      Patients who received hormone therapy were less likely to develop LR (P = 0.02).
      In the multivariate analysis, the timing of RT was not associated with a higher
      rate of LR, whereas tumor size > 2 cm and no hormone therapy were prognostic
      factors. CONCLUSIONS: In the study population, there was no increase in the risk
      of LR when RT was delayed to deliver adjuvant CT. Prognostic factors were tumor
      size, and hormone therapy. The number of CT courses could modified this risk.

PMID- 15948161
TI  - Molecular cloning of a new member of TEKTIN family, Tektin4, located to the
      flagella of rat spermatozoa.
AB  - Tektins are composed of a family of filament-forming proteins associated with
      ciliary and flagellar microtubules. A new member of the TEKTIN gene family, which
      was designated as rat Tektin4, was obtained by PCR technique combined with yeast
      two-hybrid screening. Rat Tektin4 cDNA consists of 1,341 bp encoding a 52 kDa
      protein of 447 amino acids. Tektin4 protein contains a Tektin domain including a
      nonapeptide signature sequence (RPNVELCRD), which is a prominent feature of
      Tektins. Its amino acid sequence showed 29% approximately 58% identities to that
      of other Tektin family proteins registered in the public databases. Tektin4 gene,
      which was mapped to rat chromosome 10q12, is composed of six exons and spanning 5
      kb. Reverse-transcriptional-PCR (RT-PCR) analysis indicated that Tektin4 was
      predominantly expressed in testis and its expression was upregulated during
      testis development. In situ hybridization analysis showed that Tektin4 mRNA was
      localized in round spermatids in the seminiferous tubules of the rat testis.
      Tektin4 protein was predominantly localized in the flagella of spermatozoa,
      suggesting that it might works as a flagellar component requisite for flagellar
      stability or sperm motility.

PMID- 15948162
TI  - Effects of luteinizing hormone and human chorionic gonadotropin on corpus luteum
      cells in a spheroid cell culture system.
AB  - The human corpus luteum (CL) is a highly vascularized, temporarily active
      endocrine gland and consists mainly of granulosa cells (GCs), theca cells (TCs),
      and endothelial cells (ECs). Its cyclic growth and development takes place under
      the influence of gonadotropic hormones. If pregnancy does occur, human chorionic
      gonadotropin (hCG) takes over the function of luteinizing hormone (LH) and, in
      contrast to LH, extends the functional life span of the CL. In this study, we
      investigated the effects of hCG and LH in a spheroidal cell culture model of CL
      development. Our data indicate that GCs secrete factors under the control of hCG
      that increase sprout formation of EC-spheroids. We demonstrate that the most
      prominent of these factors is VEGF-A. Furthermore, we found that both LH and hCG
      decrease sprout formation of GC-spheroids. After forming EC-GC coculture
      spheroids and consequently bringing GCs and ECs in close contact, sprouting
      increased under the influence of hCG, however not under LH. These experiments
      provide evidence for an hCG dependent functional switch in the GCs after coming
      in contact with ECs. Moreover, it demonstrates the considerably different effects
      of hCG and LH on GCs although their signaling is transmitted via the same
      receptor.

PMID- 15948163
TI  - Lipid peroxide formation in relation to membrane stability of fresh and frozen
      thawed stallion spermatozoa.
AB  - In this study we used a new method to detect reactive oxygen species (ROS)
      induced damage at the level of the sperm plasma membrane in fresh and frozen
      thawed stallion sperm. Lipid peroxidation (LPO) in sperm cells was assessed by a
      fluorescent assay involving the labeling of stallion sperm with the LPO reporter
      probe C11-BODIPY(581/591). The peroxidation dependent spectral emission shift of
      this membrane probe could be localized using inverted spectral confocal
      microscopy and quantified on living and deteriorated sperm cells using flow
      cytometry. Mass spectrometric analysis of the main endogenous lipid class,
      phosphatidylcholine (PC), was carried out to determine the formation of hydroxy-
      and hydroperoxyphosphatidylcholine in fresh sperm cells. Peroxidation as reported
      by the fluorescent probe corresponded with the presence of hydroxy- and
      hydroperoxyphosphatidylcholine in the sperm membranes, which are early stage
      products of LPO. This allowed us to correlate endogenous LPO with localization of
      this process in the living sperm cells. In absence of peroxidation inducers, only
      relatively little peroxidation was noted in fresh sperm cells whereas some mid
      piece specific probe oxidation was noted for frozen-thawed sperm cells. After
      induction of peroxidation in fresh and frozen-thawed sperm cells with the 0.1 mM
      of lipid soluble ROS tert-butylhydrogen peroxide (t-BUT) intense probe oxidation
      was produced in the mid-piece, whereas the probe remained intact in the sperm
      head, demonstrating antioxidant activity in the head of fresh sperm cells. At
      higher levels of t-BUT, probe peroxidation was also noted for the sperm head
      followed by a loss of membranes there. Frozen-thawed sperm were more vulnerable
      to t-BUT than fresh sperm. The potential importance of the new assays for sperm
      assessments is discussed.

PMID- 15948164
TI  - Factors affecting the electrofusion of mouse and ferret oocytes with ferret
      somatic cells.
AB  - The domestic ferret, Mustela putorius furos, holds great promise as a genetic
      model for human lung disease, provided that key technologies for somatic cell
      nuclear transfer (SCNT) are developed. In this report, we extend our
      understanding of SCNT in this species by defining conditions for efficient cell
      fusion by electrical pulse. Two experimental systems were employed in this study.
      First, in vivo-matured mouse oocytes and ferret somatic cells were used to
      establish general parameters for fusion. One fibroblast, or cumulus cell, was
      agglutinated to nucleate, zona pellucida-free, mouse oocytes, and subjected to an
      electrical pulse. Similar electrical pulse conditions were also tested with 1 or
      2 somatic cells inserted into the perivitelline space (PVS) of intact mouse
      oocytes. The fusion rate for a single fibroblast with a zona-free oocyte was
      80.2%, significantly higher (P < 0.05) than that observed for 1, or 2,
      fibroblasts placed in the PVS (52.0% and 63.8%, respectively). The fusion rate
      (44.1%) following insertion of two cumulus cells was significantly higher (P <
      0.05) than that following insertion of one cumulus cell (25.1%). Second, in vitro
      matured ferret oocytes were enucleated, and one to three fibroblasts or cumulus
      cells were inserted into the PVS. Zona pellucida-free ferret oocytes were fragile
      and excluded from the study. The fusion rates with two or three fibroblasts were
      71.4% and 76.8%, respectively; significantly higher (P < 0.05) than that for one
      fibroblast (48.6%). This cell number-dependent difference in fusion efficiency
      was also observed with cumulus cells. Fusion-derived (ferret-ferret) NT embryos
      cleaved, formed blastocysts in vitro, and underwent early-stage fetal development
      following embryo transfer. The rate of development was cell type-independent, in
      contrast to the cell type-dependent differences observed in fusion efficiency. In
      conclusion, fibroblasts fused more efficiently than cumulus cells and the
      efficiency of single cell fusions was improved when two or more cells were
      inserted into the PVS. These studies define conditions for efficient cell fusion
      with ferret oocytes and should facilitate SCNT and the development of genetically
      defined animal models in this species.

PMID- 15948165
TI  - Numerical chromosomal abnormalities in equine embryos produced in vivo and in
      vitro.
AB  - Chromosomal aberrations are often listed as a significant cause of early
      embryonic death in the mare, despite the absence of any concrete evidence for
      their involvement. The current study aimed to validate fluorescent in situ
      hybridization (FISH) probes to label specific equine chromosomes (ECA2 and ECA4)
      in interphase nuclei and thereby determine whether numerical chromosome
      abnormalities occur in horse embryos produced either in vivo (n = 22) or in vitro
      (IVP: n = 20). Overall, 75% of 36,720 and 88% of 2,978 nuclei in the in vivo
      developed and IVP embryos were analyzable. Using a scoring system in which extra
      FISH signals were taken to indicate increases in ploidy and "missing" signals
      were assumed to be "false negatives," 98% of the cells were scored as diploid and
      the majority of embryos (30/42: 71%) were classified as exclusively diploid.
      However, one IVP embryo was recorded as entirely triploid and a further seven IVP
      and four in vivo embryos were classified as mosaics containing diploid and
      polyploid cells, such that the incidence of apparently mixoploid embryos tended
      to be higher for IVP than in vivo embryos (P = 0.118). When the number of FISH
      signals per nucleus was examined in more detail for 11 of the embryos, the
      classification as diploid or polyploid was largely supported because 2,174 of
      2,274 nuclei (95.6%) contained equal numbers of signals for the two chromosomes.
      However, the remaining 100 cells (4.4%) had an uneven number of chromosomes and,
      while it is probable that many were artefacts of the FISH procedure, it is also
      likely that a proportion were the result of other types of aneuploidy (e.g.,
      trisomy, monosomy, or nullisomy). These results demonstrate that chromosomally
      abnormal cells are present in morphologically normal equine conceptuses and
      suggest that IVP may increase their likelihood. Definitive distinction between
      polyploidy, aneuploidy and FISH artefacts would require the use of more than one
      probe per chromosome and/or probes for more than two chromosomes.

PMID- 15948166
TI  - A physiological product-release model for baculovirus infected insect cells.
AB  - Existing models describe the product release from baculovirus infected insect
      cells as an unspecific protein leakage occurring in parallel with protein
      production. The model presented here shows that the observed product release of
      normally non-secreted proteins can be described through cell death alone. This
      model avoids the implicit non-physiological assumption of previous models that
      cells permeable to recombinant protein as well as trypan blue continue to produce
      protein.

PMID- 15948167
TI  - Capecitabine plus oxaliplatin for the first-line treatment of elderly patients
      with metastatic colorectal carcinoma: final results of the Southern Italy
      Cooperative Oncology Group Trial 0108.
AB  - BACKGROUND: In patients with metastatic colorectal carcinoma (MCC), capecitabine
      has demonstrated a superior response rate (RR), equivalent disease progression
      free (PFS) and overall survival (OS), and an improved overall tolerability
      profile compared with bolus 5-fluorouracil/leucovorin (5-FU/LV). The FOLFOX4
      regimen, combining oxaliplatin with LV and bolus plus infusional 5-FU (LV5FU2),
      has been shown to improve RR and PFS versus LV5FU2, and it was more effective and
      less toxic than irinotecan plus bolus 5-FU/LV. Capecitabine (an oral
      fluoropyrimidine) may be an effective, well tolerated, and more convenient
      alternative to 5-FU/LV in combination with oxaliplatin, especially in older
      patients. METHODS: Elderly (> or = 70 years) patients with MCC were treated with
      a 3-weekly regimen of oxaliplatin at an initial dose of 85 mg/m(2) intravenously
      on Day 1 plus capecitabine 1000 mg/m(2) orally twice daily from Days 2 to 15
      (XELOX regimen). In the absence of Grade > or = 2 hematologic toxicity,
      oxaliplatin was increased to 100 mg/m(2) in the second cycle, and in the absence
      of Grade > or = 2 nonhematologic adverse events during Cycle 2, capecitabine was
      increased to 1250 mg/m(2) twice daily in the third and subsequent cycles. After
      the first 35 patients (first series), the treatment protocol was amended so that
      only an oxaliplatin increase to 110 mg/m(2) and 130 mg/m(2) during Cycles 2 and
      3, respectively, was planned in the remaining 41 patients (second series).
      RESULTS: Seventy-six patients with a median age of 75 years (range, 70-82 years)
      entered the current study. In the first series, the oxaliplatin dose was
      increased in 18 (51%) patients, and the capecitabine dose was increased in 4
      (11%) patients. In the second series, the oxaliplatin dose was increased to 110
      mg/m(2) in 26 (63%) patients, and to 130 mg/m(2) in 19 (46%) patients. In all, 2
      complete and 29 partial responses were observed, for an overall RR of 41% (95%
      confidence interval [CI], 30-53%). The median PFS was 8.5 months (95% CI, 6.7
      10.3 months), and the median OS was 14.4 months (95% CI, 11.9-16.9 months). In a
      multivariate analysis, the presence of disease symptoms affected both PFS and OS,
      whereas OS also was independently affected by male gender and disease spread. Age
      had no independent effect on PFS or OS. Five percent of patients developed Grade
      > or = 3 hematologic toxicity during treatment, Grade 3 peripheral neuropathy
      occurred in 8% of patients, and severe hand-foot syndrome in 13% of patients.
      CONCLUSIONS: Fit elderly patients with MCC showed a good RR to XELOX with only
      mild toxicity observed in most patients. XELOX, should, therefore be considered
      as an important therapeutic option for elderly patients with MCC.

PMID- 15948168
TI  - Industrial process proteomics: alfalfa protein patterns during wet fractionation
      processing.
AB  - A proteome reference map of major soluble proteins from Medicago sativa (alfalfa)
      leaves and stems has been established for the first time. Among 195 spots
      analyzed by mass spectrometry and N-terminal Edman sequencing, 117 spots were
      unambiguously identified, representing 87 different proteins. Of these 87
      proteins, 13 proteins were directly identified from the partial genome of
      Medicago sativa, 30 from expressed sequenced tags (ESTs) of the model legume
      Medicago truncatula and 44 from closely relative species by a cross-species
      protein identification method. The proteome map of Medicago sativa was then set
      as a reference to study the major high protein content products that are
      generated during the wet fractionation process of alfalfa green biomass. Using
      two-dimensional electrophoresis, we studied the variation of the protein patterns
      at different steps of the industrial-scale process. We clearly show that the
      process induces significant changes including chemical modifications, proteolytic
      events, and heat-shock protein responses. Strikingly, a certain level of cellular
      regulation is conserved during biomass processing, as exemplified by the
      induction of some heat shock proteins. Finally, all the results obtained in this
      proteomic study may help to identify novel products and to improve process
      designs in alfalfa biomass plants.

PMID- 15948169
TI  - Effects of protein-protein interaction in ultrafiltration based fractionation
      processes.
AB  - This paper discusses the use of pulsed sample injection ultrafiltration (UF) for
      investigating protein-protein interaction, particularly its effect on protein
      transmission through UF membranes. Several binary protein mixtures were
      investigated; the proteins in each mixture being selected such that one of the
      proteins in the pair would be preferentially transmitted while the other would be
      either totally or substantially retained. The "retained" protein either decreased
      or increased or did not affect the sieving coefficient of the "transmitted"
      protein, this depending the type of protein-protein interaction, that is,
      associative, repulsive, or neutral. The type of protein-protein interaction
      depended on the particular protein pair under investigation as well as on the
      operating conditions used (pH and salt concentration). The magnitude of either
      decrease or increase in transmission of a preferentially transmitted protein due
      to the presence of a retained protein was found to be independent of the manner
      in which the proteins were injected into the system, that is, simultaneous or
      sequential. These magnitudes however correlated well with the ratio of the two
      proteins present in the feed.

PMID- 15948170
TI  - Epi-CHO, an episomal expression system for recombinant protein production in CHO
      cells.
AB  - This study describes the development of a transient expression system for CHO
      cells based on autonomous replication and retention of transfected plasmid DNA. A
      transient expression system that allows extrachromosomal amplification of
      plasmids permits more plasmid copies to persist in the transfected cell
      throughout the production phase leading to a significant increase in transgene
      expression. The expression system, named Epi-CHO comprises (1) a CHO-K1 cell line
      stably transfected with the Polyomavirus (Py) large T (LT) antigen gene (PyLT)
      and (2) a DNA expression vector, pPyEBV encoding the Py origin (PyOri) for
      autonomous plasmid amplification and encoding Epstein-Barr Virus (EBV) nuclear
      antigen-1 (EBNA-1) and OriP for plasmid retention. The CHO-K1 cell line
      expressing PyLT, named CHO-T was adapted to suspension growth in serum-free media
      to facilitate large-scale transient transfection and recombinant gene expression.
      Enhanced green fluorescent protein (EGFP) and human growth hormone (hGH) were
      used as reporter proteins to demonstrate transgene expression and productivity.
      Transfection of suspension-growing CHO-T cells with the vector pPyEBV encoding
      hGH resulted in a final concentration of 75 mg L(-1) of hGH in culture
      supernatants 11 days following transfection.

PMID- 15948171
TI  - Screening and preventive behaviors one year after predictive genetic testing for
      hereditary nonpolyposis colorectal carcinoma.
AB  - BACKGROUND: Prevention benefits from predictive genetic testing for cancer will
      only be fully realized if appropriate screening is adopted after testing. The
      current study assessed screening and preventive behaviors during 12 months after
      predictive genetic testing for hereditary nonpolyposis colorectal carcinoma
      (HNPCC) in an Australian clinical cohort. METHODS: Participants received
      predictive genetic testing for HNPCC at one of five Australian familial cancer
      clinics. Data on self-reported screening behaviors (colonoscopy, and endometrial
      sampling and transvaginal ultrasound for women) and prophylactic surgery
      (colectomy, and hysterectomy and bilateral oophorectomy for women) were collected
      using postal questionnaires before (baseline) and 12 months after receipt of
      genetic test results. Age, gender, perceived risk of cancer, and cancer-specific
      distress were assessed as predictors of colonoscopic screening. RESULTS: In the
      current study, 114 participants returned baseline questionnaires (32 carriers and
      82 noncarriers of an HNPCC mutation). Ninety-eight participants also returned a
      12-month follow-up questionnaire. Of those > or = 25 years, 73% reported having
      had a colonoscopy before genetic testing. At follow-up, 71% (15 of 25) of
      carriers and 12% (8 of 65) of noncarriers reported having a colonoscopy in the 12
      months after receipt of test results. The reduction in colonoscopy among
      noncarriers was statistically significant (P < 0.001). High perceived risk was
      associated with colonoscopy at baseline. At follow-up, mutation status was the
      only variable significantly associated with colonoscopy. Among female mutation
      carriers, 47% reported having transvaginal ultrasonography and 53% endometrial
      sampling during follow-up. There was low uptake of prophylactic surgery for
      colorectal, endometrial, or ovarian carcinomas. CONCLUSIONS: The majority of
      individuals reported appropriate screening behaviors after predictive genetic
      testing for HNPCC. The small group of noncarriers who had screening after genetic
      testing might benefit from additional counseling.

PMID- 15948172
TI  - Paclitaxel and pegylated-liposomal doxorubicin are both active in angiosarcoma.
AB  - BACKGROUND: Paclitaxel has unique activity in angiosarcomas of the face and
      scalp, but its activity in angiosarcomas originating at other sites is less well
      defined. Paclitaxel and pegylated-liposomal doxorubicin (PLD) are highly
      effective in Kaposi sarcoma (KS). Because of the efficacy of PLD in soft tissue
      sarcoma in general, and in KS in particular, coupled with potential similarities
      in KS and angiosarcoma, and the apparent activity of paclitaxel in angiosarcomas,
      the authors treated patients with angiosarcoma with either paclitaxel or PLD as
      initial chemotherapy. METHODS: To better define the efficacy of these agents in
      angiosarcoma, the authors reviewed their experience with paclitaxel and PLD in
      patients with angiosarcoma treated between 1994 and 2004. RESULTS: They
      identified seven patients with angiosarcoma treated with paclitaxel, and six
      treated with PLD. Only one patient in the series had an angiosarcoma of the
      scalp. Two patients receiving paclitaxel had received previous therapy with PLD,
      and four of six patients treated with PLD had previously received paclitaxel. Of
      the eight patients treated with paclitaxel, five had major responses (three had
      partial responses [PR] and two had complete disease remission [CR]) and three had
      progressive disease (PD). Of the 6 patients who received PLD, 3 had a PR for 6,
      19, and >20 months, respectively, 2 had stable disease for 7 and 11 months,
      respectively, and 1 had PD. CONCLUSIONS: The current study demonstrated the
      activity of PLD (five of six patients experienced clinical benefit) and extended
      the data on paclitaxel in angiosarcoma, both of the face and scalp, as well as
      angiosarcoma originating at other sites.

PMID- 15948173
TI  - Ovarian carcinoma screening in women at intermediate risk: impact on quality of
      life and need for invasive follow-up.
AB  - BACKGROUND: Women with family histories suggestive of an increased risk of
      ovarian carcinoma who have not had a deleterious BRCA1 or BRCA2 mutation
      identified are commonly suggested to consider ovarian carcinoma screening with
      transvaginal ultrasound and/or assessment of CA 125 levels. Limited information
      is available regarding the impact of this approach on either quality of life
      (QOL) or need for invasive follow-up in this group of women. METHODS: From
      November 1999 to October 2002, 184 women at intermediate risk of ovarian
      carcinoma were enrolled in a prospective study. Participants were screened with
      twice yearly transvaginal ultrasound and CA 125 assessments. Impact on QOL was
      measured using the Mental Component Summary (MCS) score of the Medical Outcomes
      Studies Short Form-36. Need for invasive follow-up was determined by
      questionnaire and medical record review. RESULTS: In the current study, 135
      participants underwent > or = 1 follow-up assessment. During a mean of 19.8
      months of follow-up, 12.9% of ultrasounds and 3.8% of CA 125 assessments were
      abnormal. The authors reported that 38.5% of participants had > or = 1 abnormal
      ovarian screen that required a short interval follow-up. Because of either
      abnormal bleeding or ultrasound abnormalities, 24% of participants underwent > or
      = 1 endometrial sampling. Controlling for a history of breast carcinoma and
      menopausal status, abnormal ovarian screening results were associated with a
      decrease in MCS score (P = 0.034), whereas the need for endometrial sampling was
      not (P = 0.87). CONCLUSIONS: Ovarian carcinoma screening in women at intermediate
      risk was associated with a substantial rate of abnormal screen results,
      endometrial sampling, and in women with abnormal ovarian screening findings, a
      decrease in MCS scores. These findings may have important implications for women
      considering ovarian carcinoma screening and for the design of future ovarian
      carcinoma screening trials.

PMID- 15948174
TI  - Integration of gene expression profiling and clinical variables to predict
      prostate carcinoma recurrence after radical prostatectomy.
AB  - BACKGROUND: Gene expression profiling of prostate carcinoma offers an alternative
      means to distinguish aggressive tumor biology and may improve the accuracy of
      outcome prediction for patients with prostate carcinoma treated by radical
      prostatectomy. METHODS: Gene expression differences between 37 recurrent and 42
      nonrecurrent primary prostate tumor specimens were analyzed by oligonucleotide
      microarrays. Two logistic regression modeling approaches were used to predict
      prostate carcinoma recurrence after radical prostatectomy. One approach was based
      exclusively on gene expression differences between the two classes. The second
      approach integrated prognostic gene variables with a validated postoperative
      predictive model based on standard variables (nomogram). The predictive accuracy
      of these modeling approaches was evaluated by leave-one-out cross-validation
      (LOOCV) and compared with the nomogram. RESULTS: The modeling approach using gene
      variables alone accurately classified 59 (75%) tissue samples in LOOCV, a
      classification rate substantially higher than expected by chance. However, this
      predictive accuracy was inferior to the nomogram (concordance index, 0.75 vs.
      0.84, P = 0.01). Models combining clinical and gene variables accurately
      classified 70 (89%) tissue samples and the predictive accuracy using this
      approach (concordance index, 0.89) was superior to the nomogram (P = 0.009) and
      models based on gene variables alone (P < 0.001). Importantly, the combined
      approach provided a marked improvement for patients whose nomogram-predicted
      likelihood of disease recurrence was in the indeterminate range (7-year disease
      progression-free probability, 30-70%; concordance index, 0.83 vs. 0.59, P =
      0.01). CONCLUSIONS: Integration of gene expression signatures and clinical
      variables produced predictive models for prostate carcinoma recurrence that
      perform significantly better than those based on either clinical variables or
      gene expression information alone.

PMID- 15948175
TI  - Purinergic mediated changes in Ca2+ mobilization and functional responses in
      microglia: effects of low levels of ATP.
AB  - Microglia, the immune effector cells of the brain, are stimulated by a diversity
      of agents to transiently increase levels of intracellular calcium ([Ca2+]i).
      Changes in [Ca2+]i induced by compounds such as adenosine triphosphate (ATP)
      serve important roles in cellular signal transduction linking stimuli with
      cellular functional responses. Purinergic responses in microglia, like that in
      other cells, are mediated by two families of receptors classified as P2Y and P2X.
      Activation of metabotropic receptors (P2YR) leads to increased [Ca2+]i due to
      depletion of intracellular stores, a process that can trigger activation of Ca2+
      entry through plasmalemmal store-operated channels (SOC). Activation of
      ionotropic receptors (P2XR) is associated with influx of Na+ and Ca2+ and efflux
      of K+ through nonselective cationic channels, leading to cellular depolarization.
      An intriguing property of purinergic stimulation of microglia is the dependence
      of cellular responses on agonist concentration. As one example, activation of the
      subtype P2X7R by higher levels of ATP (millimolar range), leads to a marked
      enhancement in microglial secretion of inflammatory mediators. Other members of
      the ionotropic P2XR family sensitive to lower levels of ATP, however, are also
      important in mediating microglial inflammatory responses in brain. At lower
      concentrations of ATP (100 microM), activation of SOC in human microglia is not
      only coupled to P2YR-dependent depletion of internal stores, but is also
      modulated by ATP binding to a P2XR (not P2X7R). The modulation is consistent with
      a P2XR-mediated influx of Na+ and inhibition of SOC by depolarization. In this
      review, a primary focus is placed on the effects of low concentrations of ATP (<
      or =100 microM) to induce changes in [Ca2+]i and modify functional processes in
      microglia. In essence, responses mediated by purinergic receptors other than
      P2X7R are considered.

PMID- 15948176
TI  - Norepinephrine protects cortical neurons against microglial-induced cell death.
AB  - Interleukin-1 beta (IL-1beta) is one of the main cytokines involved in the
      inflammatory response; it has multiple effects that can contribute to cell
      damage, one of which is the upregulation of the inducible form of nitric oxide
      (NO) synthase (NOS2) in certain cell types. We demonstrated previously that in
      vivo, cortical microglial inflammatory responses were increased when
      noradrenaline (NE) levels were depleted, suggesting that NE can reduce microglial
      activation. In the present report, we examined the role of IL-1beta in
      neurotoxicity induced by microglial-conditioned media, and possible
      neuroprotective effects of NE. Incubation of cortical neurons with conditioned
      media (CM) obtained from lipopolysaccharide (LPS)-treated microglia induced
      neuronal NOS2 expression and increased neuronal cell death, and these responses
      were reduced if the neurons were coincubated with interleukin-1 receptor
      antagonist. Cotreatment of microglial cells with LPS plus NE potently blocked IL
      1beta production and reduced the ability of the CM to induce neuronal NOS2 and
      cell death. These results suggest that microglial release of IL-1beta is an
      important activator of neuronal inflammatory responses, and that protective
      effects of NE upon neurons involve a reduction of microglial-derived IL-1beta.

PMID- 15948177
TI  - Visualization of microglia in living tissues using Iba1-EGFP transgenic mice.
AB  - Microglia are thought to play important roles not only in repairing injured
      tissue but in regulating neuronal activity, and visualizing the cells is very
      useful as a means of further investigating the function of microglia in vivo. We
      previously cloned the ionized calcium-binding adaptor molecule 1 (Iba1) gene,
      which is expressed selectively in microglia/microphages. To generate new
      transgenic mice to visualize microglia with enhanced green fluorescent protein
      (EGFP), we here constructed a plasmid carrying EGFP cDNA under control of the
      Iba1 promoter. This construct was injected into C57B/6 mouse zygotes, and the
      Iba1-EGFP transgenic line was developed. Fluorescent in-situ hybridization
      analysis revealed that the Iba1-EGFP transgene was located on chromosome 11D. No
      obvious defects were observed during development or in adulthood, and the EGFP
      fluorescence remained invariant over the course of at least four generations.
      Judging from the immunoreactivity with anti-Iba1 antibody, all EGFP-positive
      cells in the adult brain were ramified microglia. In the developing transgenic
      embryos, EGFP signals were detected as early as embryonic Day 10.5. The most
      prominent EGFP signals were found in forebrain, spinal cord, eye, foreleg, yolk
      sac, liver, and vessel walls. At postnatal Day 6, clear EGFP signals were
      observed in the supraventricular corpus callosum, known as "fountain of
      microglia", where ameboid microglia migrate into the brain parenchyma and mature
      into ramified microglia. Iba1-EGFP transgenic mice thus permit observation of
      living microglia under a fluorescence microscope and provide a useful tool for
      studying the function of microglia in vivo.

PMID- 15948178
TI  - Perturbations in calcium-mediated signal transduction in microglia from
      Alzheimer's disease patients.
AB  - Calcium-sensitive fluorescence microscopy has been used to study Ca2+-dependent
      signal transduction pathways in microglia obtained from Alzheimer's disease (AD)
      patients and non-demented (ND) individuals. Data were obtained from nine AD cases
      and seven ND individuals and included basal levels of intracellular Ca2+ [Ca2+]i,
      peak amplitudes (Delta[Ca2+]i) and time courses of adenosine triphosphate (ATP)
      responses and amplitudes of an initial transient response and a subsequent second
      component of Ca2+ influx through store-operated channels (SOC) induced by
      platelet-activating factor (PAF). Overall, AD microglia were characterized by
      significantly higher (20%) basal Ca2+ [Ca2+]i relative to ND cells. The
      Delta[Ca2+]i of ATP and initial phase of PAF responses, which reflect rapid
      depletion of Ca2+ from endoplasmic reticulum stores, were reduced by respective
      values of 63% and 59% in AD cells relative to amplitudes recorded from ND
      microglia. Additionally, AD microglia showed diminished amplitudes (reduction of
      61%) of SOC-mediated Ca2+ entry induced by PAF and prolonged time courses
      (increase of 60%) of ATP responses with respect to ND microglia. We have
      generally replicated these results with exposure of human fetal microglia to beta
      amyloid (5 microM Abeta1-42 applied for 24 hr). Overall, these data indicate
      significant abnormalities are present in Ca2+-mediated signal transduction in
      microglia isolated from AD patients.

PMID- 15948179
TI  - Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide(25-35)
      induced oxidative stress and the ensuing apoptosis.
AB  - We previously found that the atypical antipsychotic drugs (APDs) clozapine,
      olanzapine, quetiapine, and risperidone reduce PC12 cell death induced by
      hydrogen peroxide, N-methyl-4-phenylpyridinium ion, or beta-amyloid peptide
      (Abeta(25-35)). Such neurotoxic substances have in common the capability of
      causing oxidative stress. Atypical APDs have been used in treating schizophrenia
      and in treating psychotic symptoms of patients with Alzheimer's disease (AD), in
      which Abeta is involved by causing oxidative stress. Therefore, we hypothesized
      that atypical APDs might alleviate oxidative stress in PC12 cells, thus
      protecting them from apoptosis. PC12 cells were seeded in plates or chambers for
      24 hr and cultured for another 24 hr with olanzapine or quetiapine in the medium,
      and then the cells were cultured in the new medium containing Abeta(25-35) and/or
      olanzapine, quetiapine, but not serum, for various periods. It was shown that
      cultures treated with olanzapine + Abeta(25-35), or quetiapine + Abeta(25-35),
      had significantly higher cell viabilities and lower rates of apoptosis compared
      with the cultures exposed only to Abeta(25-35). In addition, the drugs blocked
      the activation of caspase-3 caused by Abeta(25-35). Furthermore, olanzapine and
      quetiapine prevented Abeta(25-35)-induced overproduction of intracellular
      reactive oxygen species, Abeta(25-35)-induced decrease in mitochondrial membrane
      potential, and Abeta(25-35)-induced changes in activities of the key antioxidant
      enzymes superoxide dismutase, catalase, and glutathione peroxidase. In
      consideration of the wealth of evidence linking oxidative stress to the
      pathophysiology of schizophrenia and AD, these findings give us a new insight
      into the therapeutic actions of atypical antipsychotics in patients with the
      disorders.

PMID- 15948180
TI  - Opioid receptor-like 1 (NOP) receptors in the rat dorsal raphe nucleus: evidence
      for localization on serotoninergic neurons and functional adaptation after 5,7
      dihydroxytryptamine lesion.
AB  - A high density of opioid receptor-like 1 (ORL1) receptor (also referred to as NOP
      receptor) is found in limbic areas and in regions containing monoamines, which
      are implicated in emotional activity and physiopathology of depression and
      anxiety. We aimed at defining precisely the localization of ORL1 receptors in
      dorsal raphe nucleus, by means of a lesion strategy and autoradiographic studies.
      In control rats, [3H]nociceptin and nociceptin-stimulated [35S]GTPgammaS bindings
      were found to be correlated in several brain regions. We performed in rats a
      selective destruction of serotoninergic neurons by surgical stereotaxic injection
      of 5,7-dihydroxytryptamine (5,7-DHT) in dorsal raphe nucleus. This led to a
      marked decrease in serotonin contents in striata and frontal cortices (about 
      60%) and in autoradiographic [3H]citalopram binding in posterior regions. In
      dorsal raphe nucleus, [3H]nociceptin binding was decreased to the same extent as
      [3H]citalopram binding, whereas it was unchanged in the other regions studied.
      Nevertheless, in the dorsal raphe, nociceptin-stimulated [35S]GTPgammaS binding
      was decreased to a lesser extent than [3H]nociceptin binding in 5,7-DHT-lesioned
      rats. The ratio between nociceptin-stimulated [35S]GTPgammaS binding and
      [3H]nociceptin binding was significantly increased in 5,7-DHT-lesioned rats
      compared with controls in this region. These data demonstrate 1) that ORL1
      receptors are located on serotoninergic neurons in the dorsal raphe nucleus and
      2) that, after a lesion, the functionality of remaining ORL1 receptors appears to
      be up-regulated, which could correspond to a compensatory mechanism.

PMID- 15948181
TI  - Myelin deterioration in Twitcher mice: motor evoked potentials and magnetic
      resonance imaging as in vivo monitoring tools.
AB  - We have used magnetic resonance imaging (MRI) and motor evoked potentials (MEPs)
      for monitoring disease progression within the CNS of the Twitcher mouse, the
      murine model for globoid cell leukodystrophy (GLD). GLD is a lysosomal storage
      disorder, resulting from galactocerebrosidase deficiency, causing central and
      peripheral myelin impairment, leading to death, usually during early infancy.
      Neuroradiological, electrophysiological, and pathological parameters of myelin
      maturation were evaluated in Twitcher mice between postnatal days 20 and 45.
      Healthy controls showed a gradual-appearance MRI T2-weighted hypointensity of the
      corpus callosum (CC) starting at about P30 and ending at about P37, whereas MRI
      of age-matched Twitcher mice showed a complete loss of the CC-related MRI signal.
      MEPs allowed the functional assessment of myelin maturation within corticospinal
      motor pathways and showed a progressive deterioration of MEPs in Twitcher mice
      with increased central conduction time (CCT; 5.12 +/- 0.49 msec at P27 to 6.45 +/
      1.96 msec at P32), whereas physiological CCT shortening was found in healthy
      controls (3.01 +/- 0.81 msec at P27 to 2.5 +/- 0.27 msec at P32). These findings
      were not paralleled by traditional histological stainings. Optical observation of
      Bielchowsky and Luxol fast blue-PAS stainings showed mild axonal/myelin
      deterioration of the Twitcher brain within this time frame. Our results
      demonstrate that serial MRI and MEP readings are sensitive evaluation tools for
      in vivo monitoring of dysmyelination in Twitcher mice and underscore their
      potential use for longitudinal evaluation of the therapeutic impact of gene and
      cell therapies on these animals.

PMID- 15948182
TI  - Association of heat shock proteins and neuronal membrane components with lipid
      rafts from the rat brain.
AB  - Lipid rafts are specialized plasma membrane microdomains enriched in cholesterol
      and sphingolipids that serve as major assembly and sorting platforms for signal
      transduction complexes. Constitutively expressed heat shock proteins Hsp90,
      Hsc70, Hsp60, and Hsp40 and a range of neurotransmitter receptors are present in
      lipid rafts isolated from rat forebrain and cerebellum. Depletion of cholesterol
      dissociates these proteins from lipid rafts. After hyperthermic stress, flotillin
      1, a lipid raft marker protein, does not show major change in levels. Stress
      inducible Hsp70 is detected in lipid rafts at 1 hr posthyperthermia, with the
      peak levels attained at 24 hr, suggesting that Hsp70 may play roles in
      maintaining the stability of lipid raft-associated signal transduction complexes
      following neural stress.

PMID- 15948183
TI  - The new Wolf-Hirschhorn syndrome critical region (WHSCR-2): a description of a
      second case.
AB  - The Wolf-Hirschhorn syndrome (WHS), is a well known contiguous gene syndrome
      characterized by microcephaly, hypertelorism, prominent glabella, epicanthal
      folds, cleft lip or palate, cardiac defects, growth and mental retardation and
      seizures. The currently accepted WHS critical region (WHSCR) is localized between
      the loci D4S166 and D4S3327, where a deletion seems to generate all the clinical
      manifestations of the syndrome. Here we present a patient with a subtelomeric
      deletion of 4p16.3 showing growth and psychomotor delay with a typical WHS facial
      appearance and two episodes of seizures in conjunction with fever. The high
      resolution G-banded karyotype was normal. Fluorescence in situ hybridization
      (FISH) with a set of cosmids from 4p16.3, showed that the deletion in this
      patient was from the D4S3327 to the telomere, enabling the size of the deletion
      to be estimated as 1.9 Mb, excluding the accepted WHSCR deletion. This patient
      supports the recent proposal by Zollino et al. [2003] that the critical region
      for WHS is located distally to the WHSCR between the loci D4S3327 and D4S98
      D4S16, and it is called "WHSCR-2" [Zollino et al., 2003].

PMID- 15948184
TI  - Studies of sperm from mutant mice suggesting that two neurotransmitter receptors
      are important to the zona pellucida-initiated acrosome reaction.
AB  - Two sperm neurotransmitter receptor/channels, the glycine receptor (GlyR) and a
      nicotinic acetylcholine receptor containing an alpha7 subunit (alpha7nAChR) were
      previously shown to be important to the mouse acrosome reaction (AR) initiated by
      solubilized egg zona pellucida (ZP). Here, we investigated whether sperm from
      homozygous mutant mice with a single amino acid mutation in the alpha subunit of
      their GlyR and sperm from homozygous mutant mice with an engineered disruption of
      the gene for the nicotinic acetylcholine receptor alpha7 subunit could undergo
      the AR on ZP-intact eggs. Wild-type and mutant sperm were treated with 3
      quinuclidinyl benzilate (QNB), known to be an inhibitor of the ZP-initiated AR
      (but shown in the present work not to inhibit the acetylcholine-initiated AR).
      The ZP-initiated AR on ZP-intact eggs should occur only in sperm not treated with
      QNB. The absence of such an increase in the untreated mutant sperm would
      demonstrate that such sperm were unable to respond to the intact ZP. The results
      demonstrated for the first time that GlyR mutant sperm do not undergo the AR on
      ZP-intact mouse eggs, and that their ability to fertilize is inhibited by 63% in
      vitro. Moreover, we found that GlyR mutant sperm exhibited normal capacitation
      and confirmed that they not undergo the AR initiated by solubilized mouse ZP. Our
      studies demonstrated for the first time that sperm from mutant alpha7nAChR mice
      exhibit normal capacitation, do not undergo the AR in response to acetylcholine,
      solubilized ZP or on ZP-intact eggs, and display a 25% reduction in fertilization
      in vitro. This is the first genetic evidence for the importance of the
      alpha7nAChR in the ZP-initiated AR. While defects in either the GlyR or the
      alpha7nAChR completely inhibit the ZP-initiated AR, fertilization by these mutant
      sperm can still occur in vitro, probably due to sperm that complete spontaneous
      AR on the ZP.

PMID- 15948185
TI  - Microarrays and expression profiling in microglia research and in inflammatory
      brain disorders.
AB  - Expression profiling by using microarrays is a powerful tool for investigating
      transcriptional changes in a variety of diseases. In this survey, microarray data
      selected from the literature from in vivo and in vitro studies are scrutinized to
      find differentially expressed genes in common within specific inflammatory
      conditions in brain or microglial cell cultures, if there are at least two
      independent investigations available. Viral encephalitis, multiple sclerosis,
      epileptic seizures, ischemic lesions, and traumatic brain injury are the
      disorders covered. Moreover, by taking into account expression data obtained from
      cultured microglia, two examples are presented of how one can deal (or should not
      deal) with lists of candidate genes showing up in these kinds of studies without
      sophisticated software programs. Finally, some general remarks are made about
      pivotal issues when beginning to use microarray technology.

PMID- 15948186
TI  - Dentatorubral-pallidoluysian atrophy in three generations, with clinical courses
      from nearly asymptomatic elderly to severe juvenile, in an Australian family of
      Macedonian descent.
AB  - We report a three-generation Caucasian family of Macedonian origin with
      dentatorubral-pallidoluysian atrophy (DRPLA), manifesting as very mild elderly
      onset, severe young adult onset, and severe childhood onset presentations in the
      three generations. The grandparental trinucleotide expansion size (52 repeats) is
      the smallest overtly pathogenic mutation yet reported. This 67-year-old man
      displayed only subtle neurological and cognitive deficits on formal examination
      and very slight signs on MRI. His son had developed a choreiform disorder at age
      32 years, and by his 40s suffered severe dementia and motor decline. The
      grandson, the proband, presented as a teenager with progressive myoclonic
      epilepsy, dysarthria, ataxia, and cognitive decline, having manifesting learning
      difficulties from the age 5 years. Atrophin-1 expansion sizes of 52, 57, and 66
      repeats were demonstrated in the three patients, respectively. Given an absence
      of any other indicative history in the family, we speculate that the mutation may
      have expanded from a 'high-end' normal allele to a pathogenic size at the
      grandfather's conception, or that one of his parents may have had a pathogenic
      mutation at the lowest end of the expanded range.

PMID- 15948187
TI  - Characterization of six marker chromosomes by comparative genomic hybridization.
AB  - We applied comparative genomic hybridization (CGH) in six patients with de novo
      prenatal or postnatal extra marker chromosomes (MC). In four cases, MCs were
      mosaic and in one of them, the MC was detected in less than 50% of the cells. In
      three cases, CGH identified the origin of the extra MCs. In the other three, two
      prenatal cases and one child with an abnormal phenotype, CGH showed normal
      profiles. Among these cases, a normal profile and entirely C-band positive was
      identified suggesting that MC did not contain euchromatin. Genetic imbalances
      detected by CGH were as follow: a gain of 8p10-p12 in a boy with facial
      dysmorphism, hyperactivity and speech delay, a gain of 8q10-q12 in a healthy man
      with a history of spontaneous abortions, and a gain of 15q11-q13 in a girl with
      speech delay, and motor skill and object manipulation difficulties. Clinical data
      of these patients were compared with those reported in the literature. We
      conclude that CGH is a very useful and powerful tool for characterizing prenatal
      or postnatal MCs, even when the mosaicism is present and the MCs are present in
      less than 50% of the cells.

PMID- 15948188
TI  - Microglia and multiple sclerosis.
AB  - Microglia participate in all phases of the multiple sclerosis (MS) disease
      process. As members of the innate immune system, these cells have evolved to
      respond to stranger/danger signals; such a response within the central nervous
      system (CNS) environment has the potential to induce an acute inflammatory
      response. Engagement of Toll-like receptors (TLRs), a major family of pattern
      recognition receptors (PRRs), provides an important mechanism whereby microglia
      can interact with both exogenous and endogenous ligands within the CNS. Such
      interactions modulate the capacity of microglia to present antigens to cells of
      the adaptive immune system and thus contribute to the initiation and propagation
      of the more sophisticated antigen-directed responses. This inflammatory response
      introduces the potential for bidirectional feedback between CNS resident and
      infiltrating systemic cells. Such interactions acquire particular relevance in
      the era of therapeutics for MS because the infiltrating cells can be subjected to
      systemic immunomodulatory therapies known to change their functional properties.
      Phagocytosis by microglia/macrophages is a hallmark of the MS lesion; however,
      the extent of tissue damage and the type of cell death will dictate subsequent
      innate responses. Microglia/macrophages are armed with a battery of effector
      molecules, such as reactive nitrogen species, that may contribute to CNS tissue
      injury, specifically to the injury of oligodendrocytes that is associated with
      MS. A therapeutic challenge is to modulate the dynamic properties of
      microglia/macrophages so as to limit potentially damaging innate responses, to
      protect the CNS from injury, and to promote local recovery.

PMID- 15948189
TI  - Neuroprotective role of microglia expressing interleukin-4.
AB  - Little is known about the underlying mechanisms responsible for the death of
      activated microglia and the functional consequences of the death of these cells,
      especially in vivo. We show here that intracortical injection of
      lipopolysaccharide (LPS) led to upregulation of interleukin-4 (IL-4)
      immunoreactivity, followed by a substantial loss of microglia 3 days later, as
      visualized by complement receptor type 3 (OX-42) immunostaining and tomato lectin
      staining. Cells positive for caspase-3 and terminal deoxynucleotidyl transferase
      mediated fluorescein-dUTP nick-end labeling (TUNEL) were also localized within
      LPS-activated microglia. IL-4 immunoreactivity was detected as early as 12 hr
      post-LPS, disappearing at 72 hr. Surprisingly, IL-4 immunoreactivity was detected
      exclusively in microglia, but not in astrocytes or neurons. In addition, IL-4
      neutralizing antibodies markedly increased the survival of activated microglia at
      3 days post-LPS. The expression of inducible nitric oxide synthase (iNOS) and
      tumor-necrosis factor (TNF)-alpha was sustained in parallel in activated
      microglia, consequently increasing neuronal cell death. To our knowledge, this
      study is the first to show the endogenous expression of IL-4 in LPS-activated
      microglia in vivo. Our findings suggest that IL-4 may regulate brain inflammation
      by inducing the death of activated microglia in vivo and increasing neuronal
      survival.

PMID- 15948190
TI  - Involvement of extracellular regulated kinase and p38 kinase in hippocampal
      seizure tolerance.
AB  - The mechanisms underlying brain seizure tolerance, a phenomenon in which brief
      periods of seizures protect brain against the lethal effects of subsequent
      sustained seizures, are poorly understood. Because brain seizure tolerance and
      brain ischemia tolerance likely share certain common mechanisms, the recent
      evidence that activation of extracellular regulated kinase (ERK) and p38 kinase
      pathways plays a critical role in ischemic preconditioning suggests that a
      similar mechanism may underlie brain seizure tolerance. We investigated the
      hypothesis in a rat kainic acid preparation of seizure preconditioning and
      tolerance, which was established by induction of one episode of priming epileptic
      status lasting for 20 min on the first day and another episode of sustained
      epileptic status lasting for 2 hr on the second day. We observed that acute
      seizures lead to a rapid activation of ERK and p38 in the hippocampal CA3 area,
      the brain region most susceptible to the lethal effects of epileptic status.
      Pretreatment with the ERK inhibitor PD98059 and the p38 inhibitor SB203580
      selectively reduces seizure-elicited activation of ERK and p38, respectively, and
      significantly reduces priming seizure-induced protection of CA3 neurons. These
      findings indicate that, similar to brain ischemia tolerance, brain seizure
      tolerance also involves the ERK and p38 signaling pathways.

PMID- 15948191
TI  - Cobalt chloride induces neurite outgrowth in rat pheochromocytoma PC-12 cells
      through regulation of endothelin-2/vasoactive intestinal contractor.
AB  - We investigated whether endothelin-2/vasoactive intestinal contractor (ET-2/VIC)
      gene expression, upregulated by hypoxia in cancer cells, was associated with
      differentiation in neuronal cells. RT-PCR analysis, morphological observations,
      and immunostaining revealed that CoCl2, a hypoxic mimetic agent, at 200 microM
      increased expression of the ET-2/VIC gene, decreased expression of the ET-1 gene,
      and induced neurite outgrowth in PC-12 rat pheochromocytoma cells. These effects
      induced by 200 microM CoCl2 were completely inhibited by the antioxidant N-acetyl
      cysteine at 20 mM. In addition, CoCl2 increased the level of intracellular
      reactive oxygen species (ROS) at an early stage. Furthermore, interleukin (IL)-6
      gene expression was upregulated upon the differentiation induced by CoCl2. These
      results suggest that expression of ET-2/VIC and ET-1 mediated by ROS may be
      associated with neuronal differentiation through the regulation of IL-6. When the
      cells were treated with 500 microM CoCl2 for 24 hr, however, ET-2/VIC gene
      expression disappeared, IL-6 gene expression was downregulated, and necrosis was
      subsequently induced in the PC-12 cells.

PMID- 15948192
TI  - Is Dandy-Walker malformation associated with "distal 13q deletion syndrome"?
      Findings in a fetus supporting previous observations.
AB  - We report on a fetus with a large deletion of the distal part of the long arm of
      chromosome 13, (del(13)(q14 --> qter)) congenital anomalies of the urinary
      system, lungs and extremities, and Dandy-Walker malformation (DWM). Although DWM
      has been associated with many chromosomal abnormalities and genetic syndromes,
      its relation to the distal 13q has been demonstrated recently. In 2002, McCormack
      et al., described two patients with deletions of the long arm of chromosome 13
      who had multiple congenital abnormalities along with holoprosencephaly (HPE) and
      DWM. The phenotypic features and autopsy findings of a fetus with "distal 13q
      deletion syndrome" at 22 weeks gestation are discussed and comparison with the
      previous two cases is made. The findings support the previous hypothesis
      suggesting that haploinsufficiency at a locus within 13q22-33 due to
      microdeletions may be responsible for isolated DWM in some of the patients.
      Detailed examination of 13q (13q22-33) by means of conventional and molecular
      cytogenetic methods is necessary in cases with DWM.

PMID- 15948194
TI  - New case of contiguous gene syndrome at chromosome 8p11.2p12.

PMID- 15948193
TI  - Neurofibromatosis-Noonan syndrome: molecular evidence of the concurrence of both
      disorders in a patient.
AB  - Noonan syndrome (NS) is an autosomal dominant disorder characterized by short
      stature, facial anomalies, webbed neck, sternal deformity, heart defects, and, in
      males, cryptorchidism. PTPN11 encodes SHP2, an important component of several
      signal transduction pathways that acts as a positive regulator of RAS-mitogen
      activated protein kinase signaling. Neurofibromatosis type 1 (NF1) is another
      autosomal dominant disorder characterized by hamartomas in multiple organs. The
      NF1 gene encodes a GAP-related protein, which acts as a negative regulator of the
      Ras-mediated signal transduction pathway. Clinical overlap between both
      syndromes, neurofibromatosis-Noonan syndrome (NFNS) is well known. We studied a
      female patient with typical findings of NFNS and found two mutations: a novel
      PTPN11 transversion, 1909A --> G, resulting in Gln510Arg, and an NF1
      transversion, 2531A --> G, resulting in Leu844Arg. She inherited the PTPN11
      mutation from her father and had a de novo NF1 mutation. This is the first report
      of molecular concurrence of both disorders in the same patient.

PMID- 15948195
TI  - Mutation spectrum in Jewish cystic fibrosis patients in Israel: implication to
      carrier screening.
AB  - We have tested 144 unrelated Jewish patients suffering from the classical form of
      cystic fibrosis. The patients were screened for a panel of 12 mutations including
      the six Ashkenazi founder mutations (DeltaF508, W1282X, N1303K, G542X, 3849 + 10
      kb C-->T, 1717-1G > A) and six mutations that were found in non-Ashkenazi Jewish
      patients (S549R (T-->G), G85E, 405 + 1G-->A, W1089X, Y1092, and D1152H). Patients
      of Georgian origin were tested also for the Q359K/T360K mutation. In addition,
      all the patients were tested for the IVS-8 variant (9T/7T/5T). Of all the cystic
      fibrosis (CF)-bearing chromosomes, 94% (264/281) were accounted for by one of the
      known mutations, and none of the patients had the 5T allele of the IVS-8 variant.
      Single strand conformation polymorphism (SSCP) analysis of the coding sequence of
      the CFTR gene followed by sequencing showed eight mutations on ten CF
      chromosomes, leaving seven chromosomes (2.5%) with unknown mutations. We
      identified three mutations in two or more CF chromosomes, 2571 + 1insT in Jews
      from Iraq, 3121-1G > A in patients from Kurdistan and I1234V in Yemenite Jewish
      patients. The other five mutations appeared on a single allele and are considered
      "private mutations." In this study we have identified 99% of CF alleles in
      Ashkenazi Jewish patients, 91% in Jews of North African origin and 75% in Jewish
      patients from Iraq. The significance of these findings to the population
      screening in Israel is discussed.

PMID- 15948196
TI  - Variations of the CFTR gene in the Hanoi-Vietnamese.
AB  - In order to investigate polymorphic backgrounds of the cystic fibrosis
      transmembrane conductance regulator gene (CFTR) in the Vietnamese, we analyzed
      495 blood samples of randomly selected healthy individuals in Hanoi for the delta
      F508 mutation and TG-repeats, poly-T, and M470V polymorphisms. We compared their
      distributions with those of Caucasians and other Asian populations. No delta F508
      mutation was found, being consistent with the extremely low incidence of cystic
      fibrosis (CF) in Vietnam. Allele frequency of the T5 allele promoting exon 9
      skipping was 0.037. Greater number of TG-repeats, which is known to facilitate
      this aberrant splicing, was a predominant trend in the Vietnamese and other
      Asians. A "T5-TG12-V470" haplotype was most common (29/37) among T5-bearing
      haplotypes. Three major haplotypes, T7-TG12-M470, T7-TG11-V470, and T7-TG12-V470,
      estimated by PHASE program, related to 92% of the population. This is the first
      study of the CFTR gene among the Vietnamese.

PMID- 15948197
TI  - Association of Adams-Oliver syndrome with pulmonary arterio-venous malformation
      in the same family: a further support to the vascular hypothesis.
AB  - Adams-Oliver syndrome (AOS) is a rare disease characterized by congenital scalp
      defects, terminal transverse limb defects and cutis marmorata telangiectatica. A
      significant incidence of cardiac and vascular malformations has been reported,
      leading to the hypothesis of a vascular defect early involved in the
      pathogenesis. We report two members of the same family with previously diagnosed
      AOS based on clinical phenotype and later recognized to have pulmonary arterio
      venous malformation (PAVM). None of the subjects fulfilled current diagnostic
      criteria of hereditary hemorrhagic telangiectasia, which is the most common cause
      of PAVM. The occurrence of PAVM in AOS lends support to the hypothesis that
      endothelial specific abnormalities could be a patho-physiological mechanism in
      its development. Therefore, the role of screening for PAVM in clinical management
      of subjects with AOS should deserve further studies.

PMID- 15948198
TI  - Lymphocytes and the foreign body response: lymphocyte enhancement of macrophage
      adhesion and fusion.
AB  - The host foreign body response ensues immediately following implantation of
      medical devices and prostheses. We have previously identified the role of
      macrophages in adhering to biomaterial surfaces and guiding the foreign body
      response while fusing into foreign body giant cells (FBGCs) and concentrating
      degradative and phagocytic activities. Despite their early and transient presence
      around implanted biomaterials, few studies have focused on the role of
      lymphocytes in the foreign body response and biocompatibility. To address this,
      an in vitro human lymphocyte/macrophage coculture system has been developed.
      Using this system, it has been shown that when lymphocytes are present during the
      initial adhesion of monocytes, the rate of monocyte adhesion and fusion is
      significantly increased (1,500 cells/mm2 and 60%, respectively) when compared to
      either no lymphocytes present (500 cells/mm2 adhesion and 0% fusion). Although
      lymphocytes adhered to the tissue culture polystyrene surface, 90% of the
      lymphocytes were associated with adherent macrophages. However, these cell-cell
      direct interactions were not necessary to influence macrophage adhesion or fusion
      as separating the two cell types by a Transwell insert still resulted in
      significantly increased levels of macrophage adhesion (p < 0.05 when compared to
      macrophage only cultures). Conversely, the presence of macrophages in Transwell
      experiments increased lymphocyte proliferation rates at all time points tested.
      These studies begin to detail the interactions between lymphocytes and
      macrophages in the absence of known antigen that appropriately relates to the
      scenarios experienced upon implantation of biomedical devices and the initiation
      of the foreign body response.

PMID- 15948199
TI  - Mutation in the von Willebrand factor-A domain is not a prerequisite for the
      MATN3 mutation in multiple epiphyseal dysplasia.

PMID- 15948200
TI  - Three-dimensional topography of the motor endplates of the rat gastrocnemius
      muscle.
AB  - Spatial distribution of motor endplates affects the shape of the electrical
      activity recorded from muscle. In order to provide information for realistic
      models of action potential propagation within muscles, we assembled three
      dimensional maps of the motor endplates of the rat medial gastrocnemius (MGM) and
      lateral gastrocnemius (MGL) muscles. The maps were assembled from histological
      cross sections stained for acetylcholinesterase activity. Within MGL, the motor
      endplates formed three columns along its longitudinal axis. Within MGM, the motor
      endplates were arranged in a leaf-like body that shifted obliquely from proximal
      to distal. As inferred from the proximo-distal distribution of the cross
      sectional projection area, the majority of the motor endplates were concentrated
      in the middle of MGL and in the distal third of MGM. Regions of maximal motor
      endplate concentration are considered most suitable for injections of neuroactive
      substances, such as neuronal tracers. The assembled maps of the gastrocnemius
      muscles can be used as guides for such injections within the motor endplate
      zones.

PMID- 15948201
TI  - Changes in quadriceps twitch tension in response to resistance training in
      healthy sedentary subjects.
AB  - Magnetic stimulation of the femoral nerve has been shown to evoke maximal
      quadriceps twitch contraction (TwQ(max)). Its measurement as a nonvolitional
      index of muscle strength has been proposed as a means to follow the disability of
      patients with neuromuscular disorders or peripheral muscle weakness. The aim of
      the present study was to investigate TwQ(max) sensitivity to interventions known
      to develop peripheral muscle strength. We thus measured changes in TwQ(max) after
      a short-duration resistance training program, examining its reproducibility and
      comparing its changes with other indices of muscle strength, such as maximal
      voluntary contraction (MVC) and one-repetition maximum (1-RM). In 23 subjects,
      TwQ(max)was measured on two occasions. High within- and between-session
      intraclass coefficients of correlation were observed (r > 0.99). Within-session
      and between-session differences in TwQ(max)were low (2.2 +/- 1% and 5.4 +/- 2%,
      respectively). Eight subjects subsequently participated in a resistance training
      program of the knee extensors, 3 days per week for 8 weeks. TwQ(max) and 1-RM
      increased significantly after training (10.9 +/- 3.7 vs. 12.3 +/- 4.4 kg, P <
      0.04; and 45 +/- 13 vs. 55 +/- 12 kg, P < 0.001, respectively), whereas the MVC
      increase did not reach significance (41.9 +/- 16 kg vs. 42.3 +/- 15 kg, P =
      0.25). Responses to magnetic stimulation of the femoral nerve are highly
      reproducible and sensitive enough to detect improvement in muscle contractile
      mechanisms after resistance training in healthy subjects. Patient cooperation is
      not required, which may be an advantage in clinical situations.

PMID- 15948202
TI  - Electrical impedance myography in the detection of radiculopathy.
AB  - Electrical impedance myography (EIM) is a new bioimpedance-based technique for
      neuromuscular disease assessment. Past work has focused on EIM in the evaluation
      of diffuse diseases (such as myopathy). In this study, the method's most basic
      form, linear-EIM, was used for the assessment of restricted radiculopathic
      disease. Ten normal subjects and 10 patients with unilateral cervical or
      lumbosacral radiculopathy, diagnosed by electromyography and clinical criteria,
      were enrolled. Linear-EIM was performed bilaterally on all individuals, and
      comparisons with the major outcome variable, theta(avg), were made. In normal
      subjects, side-to-side differences in theta(avg) averaged 0.64% and were no
      greater than 15.9% in magnitude. In the 10 patients with radiculopathy,
      theta(avg)was consistently lower in the affected extremity, with a mean side-to
      side difference of 15.3%, but ranging as low as 72.3%; there was a tendency for
      muscles with more prominent chronic neurogenic change to show greater relative
      reductions in theta(avg). These findings support the potential utility of EIM in
      assessment of localized neuromuscular disease.

PMID- 15948203
TI  - Ultrastructure of bone healing in defects grafted with a copolymer of
      polylactic/polyglycolic acids.
AB  - Bone substitutes have been used for the treatment of bone defects. The objective
      of this study was to ultrastructurally evaluate the healing pattern of bone
      defects filled with a copolymer of polylactic/polyglycolic acid (FisiograftR) at
      a time point in which it is expected to be only partially degraded, with the
      purpose to ultrastructurally analyze how the bone is forming around the grafting
      material. Three 5-mm-diameter bone defects were created in each tibia from 5
      rabbits (average weight 2.5 kg) in which the material was randomly implanted.
      Animals were sacrificed 30 days after surgery and the 30 bone defects were fixed
      in 2% glutaraldehyde-2.5% formaldehyde, under microwave irradiation, decalcified
      in EDTA, embedded in Spurr resin, and examined in a Jeol 1010 TEM. All the bone
      defects were filled with connective tissue, interspersed with different amounts
      of the filling material and newly formed bone trabeculae. In areas where the
      degrading copolymer was present in small amounts, newly formed bone matrix was
      detected; it was deposited by osteoblast-like cells in close relation to the
      copolymer. In areas where the degrading copolymer formed accumulates, an
      amorphous multilayered material was identified between the connective tissue and
      the copolymer. In summary, the copolymer of PLA/PGA studied appears to be an
      osteoconductive material when it is used to fill bone defects.

PMID- 15948204
TI  - Combined femoral and obturator neuropathy caused by synovial cyst of the hip.
AB  - A 57-year-old man with a history of severe degenerative lumbar spine disease
      presented with painful proximal weakness of the right leg. Clinical examination
      suggested a femoral and obturator neuropathy with a palpable mass in the right
      groin. Magnetic resonance (MR) imaging disclosed a large synovial cyst of the
      underlying hip joint in the extrapelvic part of the iliopsoas and external
      obturator muscles, with femoral and obturator nerve compression. This case
      highlights the importance of detailed clinical examination in patients with
      multiple joint disease, the need for considering space-occupying cysts of
      degenerated joints as a potential cause of nerve damage in unusual locations, and
      the value of multiplanar MR imaging for proper diagnosis in such situations.
      Muscle Nerve, 2005.

PMID- 15948205
TI  - Acquired nucleic acid changes may trigger sporadic amyotrophic lateral sclerosis.
AB  - This article brings together evidence to support the hypothesis that acquired
      nucleic acid changes are the proximate causes, "triggers," or "initiators" of
      sporadic amyotrophic lateral sclerosis (ALS). Clinical features that support this
      hypothesis include focal onset and spread, and the individualized rate of
      progression. Clues from the epidemiology of sporadic ALS include the increase in
      its incidence with age, suggesting accrual of time-dependent changes, and the
      emergence of smoking, a known carcinogen, as its first "more likely than not"
      exogenous risk factor. The identification of any exogenous risk factor suggests
      that a large proportion of sporadic cases have a triggering mechanism susceptible
      to that factor. Ingestion of the products of cycad circinalis has been
      hypothesized to be implicated in causing Western Pacific ALS. Cycad contains both
      neurotoxic factors and carcinogens. The dissimilarity of Western Pacific ALS from
      neurotoxic diseases suggests a greater likelihood that the effects of DNA
      alkylation are its proximate cause.

PMID- 15948206
TI  - Calpain-dependent alpha-fodrin cleavage at the sarcolemma in muscle diseases.
AB  - To clarify the involvement of calpains in sarcolemmal remodeling, we examined the
      expression of calpains and their substrate, alpha-fodrin, in various disorders of
      muscle. Although immunohistological reactions for alpha-fodrin and calpains were
      weak in normal control muscles, intense immunoreactivity for alpha-fodrin at the
      sarcolemma and for calpains throughout the cytoplasm were detected in small
      muscle fibers from patients with inflammatory myositis (IM), rhabdomyolysis
      (Rhab), and Duchenne muscular dystrophy (DMD). Most of the calpain-alpha-fodrin
      double-positive muscle fibers in IM and Rhab also expressed the developmental
      form of myosin heavy chain. The sarcolemma of these small muscle fibers reacted
      with an antibody that specifically recognizes the 150-kDa fragments of alpha
      fodrin (SBDP 150s) cleaved by calpain, but not caspase 3. Western blot analysis
      confirmed these results. These observations indicate that calpain is activated
      and reacts with alpha-fodrin as a substrate at the sarcolemma, and plays a key
      role in modulating sarcolemmal proteins to adapt to the specific conditions in
      each myopathy.

PMID- 15948207
TI  - Streptomycin and EDTA decrease the number of desmin-negative fibers following
      stretch injury.
AB  - Streptomycin and ethylene diamine tetraacetic acid (EDTA) were used to examine
      the role of extracellular calcium in stretch-induced muscle injury. Streptomycin
      was injected in one group of rats, three times daily for 8 days (S, 300 mg.kg(
      1).day(-1) intraperitoneally). In another group, EDTA was administered (150
      mg.kg(-1) IP) 20 min before and 24 h after the injury protocol. Untreated rats
      (C) served as controls. Muscle injury was produced by 40 stretches of active
      dorsiflexor muscles by ankle rotation from 80 degrees to 130 degrees (velocity
      1.75 rad.s(-1)). Ten minutes after the injury protocols, all animals lost the
      same amount of isometric force at both low and high stimulation frequencies (20
      HZ; S, 56 +/- 6%; EDTA, 47 +/- 7%; C, 55 +/- 4%) and 120 HZ; S, 11 +/- 3%, EDTA,
      13 +/- 3%; C, 11 +/- 3%). Tibialis anterior (TA) muscles were removed after 48 h
      for morphometric analysis. In both streptomycin-and EDTA-treated rats, the
      percent of injured (i.e., desmin-negative) myofibers in TA was reduced compared
      to untreated, injured muscles (S, 0.35 +/- 0.08%; EDTA, 0.64 +/- 0.19%; C, 1.81
      +/- 0.43%). Thus, streptomycin and EDTA treatment did not alter the development
      of muscle weakness (i.e., isometric force deficit), but almost abolished the
      histopathologic changes. This study shows that the mechanisms for muscle weakness
      and histopathologic changes (inflammation) following repeated muscle strains can
      largely be dissociated from each other and helps explain why there is no
      correlation between isometric force deficits and the number of pathologic cells.

PMID- 15948208
TI  - Fibroblast growth factor-2 immunoreactivity is present in the central and
      peripheral auditory pathways of adult rats.
AB  - Recent findings have pointed out the role of neurotrophic factors in the survival
      and maintenance of neurons of the auditory system. Basic fibroblast growth factor
      (bFGF, FGF-2) is a potent neurotrophic molecule whose actions can be seen in the
      central and peripheral nervous systems. In the present study, FGF-2
      immunoreactivity was analyzed in the auditory pathways of the adult rat,
      employing a well-characterized polyclonal antibody against FGF-2. In the cochlea,
      FGF-2 immunoreactivity was observed in the inner and outer hair cells of the
      organ of Corti, spiral ganglion neurons, spiral limbus, and stria vascularis.
      Stereological methods employing optical fractionator revealed the presence of
      84.5, 15, and 0.5% of spiral ganglion neurons possessing FGF-2 immunoreactivity
      of strong, moderate, and weak intensity, respectively. In the central auditory
      pathways, FGF-2 immunoreactivity was found in the cytoplasm of the neurons of the
      cochlear nuclei, trapezoid body nuclei, medial geniculate nucleus, and inferior
      colliculus. The two-color immunoperoxidase method showed FGF-2 immunoreactivity
      in the nuclei of astrocytes throughout the central auditory pathway. Computer
      assisted microdensitometric image analysis revealed higher levels of specific
      mean gray values of FGF-2 immunoreactivity in the trapezoid body and ventral
      cochlear nucleus and also in the spiral ganglion and inner hair cells. Sections
      incubated with FGF-2 antibody preabsorbed with human recombinant FGF-2 showed no
      immunoreaction in the majority of the studied regions, exhibiting only a slight
      immunoreactive product in the hair cells of the organ of Corti. Furthermore, no
      changes in immunoreactivity were observed in sections incubated with FGF-2
      antiserum preincubated with human recombinant acidic FGF (FGF-1). The findings
      suggest that FGF-2 may exert paracrine and autocrine actions on neurons of the
      central and peripheral auditory systems and may be of importance in the mechanism
      of hearing diseases.

PMID- 15948209
TI  - An onion phase in salt-free zero-charged catanionic surfactant solutions.

PMID- 15948210
TI  - Scanning the beta-globin gene for mutations in large populations by denaturing
      capillary and gel electrophoresis.
AB  - Separation of mutant from nonmutant DNA sequences of 100 bp may be accomplished
      by using defined denaturing conditions of chemical denaturant and/or elevated
      temperature during electrophoresis on either polyacrylamide slab gels (denaturing
      gradient gel electrophoresis, DGGE) or capillary gels (constant denaturant
      capillary electrophoresis, CDCE). In analysis of mutant directly from a
      polymerase chain reaction (PCR) product mixture, both have detection
      sensitivities of approximately 1%. CDCE that facilitates an intermediate mutant
      enrichment step permits detection of mutants at fractions as low as 2 x 10(-6).
      Here we report the successful application of both approaches to scan for
      mutations of the human beta-globin gene (HBB) in two human population samples of
      approximately 5000 persons in the HBB. Using DGGE, the coding region and flanking
      intronic splice sites of HBB were scanned in a population of 4949 Han Chinese
      individuals in pool sizes of 48 individual DNA samples. Four point mutations
      ranging in mutant frequency from 0.5 to 0.0002 were identified. Using CDCE with a
      mutant enrichment step, these same sequences were scanned in a population of
      5028, predominantly African-American juveniles (<9 years) as a single pooled DNA
      sample. Three point mutations were identified ranging in mutant frequency from
      0.13 to 0.0005. This study shows that both the DGGE/small pool and the CDCE/large
      pool approaches offer the means to define the fine structure map of genetic
      variation in large population samples, and with appropriately engineered
      facilities to provide high throughput, should be useful in pangenomic scans to
      discover genes carrying casual mutations for common diseases.

PMID- 15948211
TI  - Hydrolytically stable, diaminocarboxylic acid-based membranes buffering in the pH
      range from 6 to 8.5 for isoelectric trapping separations.
AB  - Diaminocarboxylic acid carrier ampholytes, such as L-histidine, 2,3
      diaminopropionic acid, L-ornithine, and L-lysine, were reacted with glycerol-1,3
      diglycidyl ether (GDGE) and poly(vinyl alcohol) (PVA) in the presence of sodium
      hydroxide to produce hydrolytically and mechanically stable hydrogels, supported
      on a PVA substrate, for use as buffering membranes in isoelectric trapping (IET)
      separations. The pH values of the DACAPVA membranes were determined with the help
      of small-molecule pI markers and proteins and were found to be in the 6 < pH <
      8.5 range. The membranes were successfully used to isoelectrically trap small
      ampholytes, desalt ampholyte solutions in IET mode, and effect the binary
      separation of chicken egg white proteins.

PMID- 15948212
TI  - Determination of caffeine and its metabolites in urine by capillary
      electrophoresis-mass spectrometry.
AB  - The caffeine content of foods and beverages varies considerably, interfering with
      our ability to obtain valid interpretations in many human studies with regard to
      the mechanism of action(s) of caffeine and/or its metabolites. The rate of
      metabolism of caffeine and other xanthine drugs also varies greatly from one
      individual to another. Therefore, it is extremely important to develop accurate,
      reliable analytical methods to quantify caffeine and its metabolites in simple
      and complex matrixes. A simple method is described for the separation and
      characterization of caffeine and its major metabolites employing capillary
      electrophoresis (CE) coupled to ultraviolet-absorption and mass spectrometry (MS)
      detection. After optimization of the electrophoresis separation conditions, a
      reliable separation of caffeine and 11 of its major metabolites was achieved in
      50 mM ammonium carbonate buffer, pH 11.0. The volatile aqueous electrolyte system
      used with a normal electroosmotic flow polarity also provided an optimal
      separation condition for the characterization of the analytes by MS. The CE
      method achieved baseline resolution for all 12 compounds in less than 30 min. The
      CE-MS method is suitable for use as a routine procedure for the rapid separation
      and characterization of caffeine and its metabolites. The usefulness of this
      method was demonstrated by the extraction, separation, and identification of
      caffeine and its 11 metabolites from normal urine samples. The urine specimens
      were first acidified to obtain optimum binding efficiency to the sorbents of the
      off-line, solid-phase extraction procedure employed here, and an acidified eluent
      solvent was employed for the desorption step to maximize the recovery of the
      bound analytes.

PMID- 15948214
TI  - CD8+ T cell contributions to allergen induced pulmonary inflammation and airway
      hyperreactivity.
AB  - The pathogenesis of asthma has been linked to the production of type 2 cytokines,
      which can be expressed by several cell types in the lung. These studies
      investigated CD8(+) T cell responses in a murine cockroach antigen (CRA) model of
      asthma. The results from these present studies show that depletion of CD8(+) T
      cells after allergen sensitization to CRA significantly reduces airway
      hyperreactivity, airway eosinophilia and pulmonary type 2 cytokine levels. The
      data demonstrate that CD8(+) T cells from CRA-sensitized mice can produce type 2
      cytokines IL-4, IL-5 and IL-13 upon antigen challenge, and that the transfer of
      these cells into naive mice will cause airway hyperreactivity when exposed to
      CRA. We found that the transferred airway response is dependent on both IL-4 and
      IL-13 from CD8(+) T cells using cytokine knockout mice. Compared to CD4(+) T
      cells, CD8(+) T cells were not as numerous in the lungs of sensitized and
      challenged mice, but were as efficacious in the transfer of airway disease. The
      most severe airway response was observed when both CD4(+) and CD8(+) T cells were
      transferred at the same time. Altogether, these studies highlight a role for
      CD8(+) T lymphocytes in the development of allergen-induced airway responses.

PMID- 15948215
TI  - Tolerant T cells display impaired trafficking ability.
AB  - Based on our previous observation that anergic T lymphocytes lose their migratory
      ability in vitro, we have proposed that anergic T cells are retained in the site
      where they have been generated to exert their regulatory function. In this study
      we have analyzed T lymphocyte trafficking and motility following the induction of
      tolerance in vivo. In a model of non-deletional negative vaccination to
      xenoantigens in which dendritic cells (DC) localize to specific lymphoid sites
      depending on the route of administration, tolerant T cells remained localized in
      the lymph nodes colonized by tolerogenic DC, while primed T cells could traffic
      efficiently. Using an oral tolerance model that enables the 'tracking' of
      ovalbumin-specific TCR-transgenic T cells, we confirmed that T cells lose the
      ability to migrate through syngeneic endothelial cell monolayers following
      tolerance induction in vivo. Finally, we show that tolerant T cells (both in
      vitro and ex vivo) can inhibit migration of responsive T cells in an antigen
      independent manner. Thus, hyporesponsive T cells localize at the site of
      tolerance induction in vivo, where they exert their anti-inflammatory properties.
      In physiological terms, this effect is likely to render immunoregulation a more
      efficient and controllable event.

PMID- 15948216
TI  - A novel apoptosis-inducing anti-PSGL-1 antibody for T cell-mediated diseases.
AB  - We previously discovered a hamster monoclonal antibody, TAB4, against mouse PSGL
      1/CD162 that can induce death of activated T cells. Here, we further investigated
      the potential of TAB4 in treating two murine models of T cell-mediated diseases.
      The results showed that administration of TAB4 suppressed incidence and severity
      of both GVHD and type I diabetes. Analyses of apoptotic T cells ex vivo shortly
      after antibody injection revealed a higher percentage of apoptosis among
      activated T cells in the TAB4-treated group than in the control group.
      Furthermore, restoration of functional donor T cells was observed in TAB4-treated
      mice. As TAB4 does not affect the binding of P-selectin to activated T cells, our
      data suggest that its long-lasting therapeutic effect on inhibiting disease
      progression is attained by specifically inducing apoptosis of activated T cells.
      These data hence extend our previous finding of the novel property of PSGL-1 and
      strongly indicate that the PSGL-1-specific apoptosis-inducing antibody is a new
      therapeutic agent possessing a great potential for controlling GVHD and other T
      cell-mediated autoimmune diseases.

PMID- 15948217
TI  - Distribution and phenotype of murine rotavirus-specific B cells induced by
      intranasal immunization with 2/6 virus-like particles.
AB  - Virus-like particles containing the rotavirus (RV) internal proteins VP2 and VP6
      (2/6-VLP) have been shown to induce serum and fecal antibodies as well as
      protection in mice after intranasal administration with a mutant of E. coli
      toxin, LT-R192G. To better understand the origin of fecal IgA induced by this
      protocol, we studied the RV-specific B cell response in systemic and mucosal
      lymphoid tissues using a flow cytometry assay that allows quantification and
      phenotypic characterization of RV-specific B lymphocytes. We also assessed the RV
      specific antibody-secreting cells in the spleen and intestinal lamina propria
      (ILP). A remarkably high frequency of RV-specific B cells was found in the
      respiratory lymphoid tissues and spleen, of which only a minority expressed the
      alpha4beta7 integrin (intestinal homing receptor). In contrast, but in accordance
      with alpha4beta7 expression at the induction site, a very low response was
      observed in intestinal lymphoid tissues (mesenteric lymph nodes and ILP), which
      did not increase after a second immunization. Thus, intranasal immunization with
      a nonreplicating antigen does not induce an important number of RV-specific B
      cells with an intestinal homing profile.

PMID- 15948218
TI  - Electrophoresis in gel channels.
AB  - We describe a novel approach to generate dynamic pH gradients suited to
      fractionate or purify samples of biomolecules or particles such as proteins and
      viruses in tiny volumes. The method combines diffusion and electromigration
      between micro-scaled channels embedded in hydrogel. For the used geometry and in
      accordance with numerical calculations the gel-channel system reaches a tuneable,
      steady-state pH gradient after a few minutes. For quantification of
      experimentally generated pH-profiles, the concentration independent extinction
      ratio of phenol red at two wavelengths is used. The proposed electrophoretic flow
      cell is simple and flexible since no Immobilines are required to establish the pH
      gradient.

PMID- 15948219
TI  - Laser-induced fluorescence detection schemes for the analysis of proteins and
      peptides using capillary electrophoresis.
AB  - Over the past few years, a large number of studies have been prepared that
      describe the analysis of peptides and proteins using capillary electrophoresis
      (CE) and laser-induced fluorescence (LIF). These studies have focused on two
      general goals: (i) development of automatic, selective and quick separation and
      detection of mixtures of peptides or proteins; (ii) generation of new methods of
      quantitation for very low concentrations (nm and subnanomolar) of peptides. These
      two goals are attained with the use of covalent labelling reactions using a
      variety of dyes that can be readily excited by the radiation from a commonly
      available laser or via the use of noncovalent labelling (immunoassay using a
      labelled antibody or antigen or noncovalent dye interactions). In this review
      article, we summarize the works which were performed for protein and peptide
      analysis via CE-LIF.

PMID- 15948220
TI  - BRAF mutation detection and identification by cycling temperature capillary
      electrophoresis.
AB  - BRAF mutations are found in many human tumors, namely melanomas ( approximately
      70%) and colon carcinomas ( approximately 15%). This paper presents a method for
      identification of exon 15 BRAF mutations by denaturant capillary electrophoresis
      (CE), an analysis method that is sensitive, cost-effective (involving only
      polymerase chain reaction (PCR) and electrophoresis) and capable of high
      throughput screening. In total, we found 21 (70%) out of 30 melanoma cell lines
      with BRAF mutations in exon 15: two of which were the p.Val600Asp (c.1799
      800TG>AT) mutation, one cell line contained the p.Val600Arg (c.1798-99GT>AG)
      mutation, and 18 cell lines contained the p.Val600Glu (c.1799T>A) mutation. Of
      the nine cell lines that did not contain a BRAF mutation, five contained an NRAS
      mutation at exon 2, and no mutations were detected in NRAS exon 1. There was no
      overlap of NRAS and BRAF mutations in the same cell line. In addition, we looked
      at 221 colon biopsy samples and identified one further BRAF mutation, the
      p.Asp594Gly (c.1781A>G) mutation, in seven samples. The p.Val600Glu mutation was
      identified in 11 of the colon biopsy samples. Using the four mutations of BRAF
      exon 15, we then constructed a denaturing CE standard capable of distinguishing
      between each of the mutations; therefore, sequencing does not need to be
      performed to confirm the mutation. In conclusion, this sensitive, cost-effective
      mutation assay for BRAF (and RAS) will provide the opportunity to detect and
      determine mutations without the need to purify samples for sequencing. Future
      large-scale studies will provide the clinical usefulness of such mutations.

PMID- 15948224
TI  - Stem cell implantation in ischemic mouse heart: a high-resolution magnetic
      resonance imaging investigation.
AB  - Advances in the biology of stem cells have evoked great interest in cell
      replacement therapies for the regeneration of heart tissue after myocardial
      infarction. However, results from human trials are controversial, since the
      destination of the injected cells, their engraftment and their long-term fate
      have remained unclear. Here we investigate whether transplanted cells can be
      identified in the intact and lesioned murine myocardium employing high-resolution
      MRI. Cardiac progenitor cells, expressing the enhanced green fluorescent protein
      (EGFP), were labeled with ultra-small paramagnetic iron-oxide (USPIO)
      nanoparticles and transplanted into the intact or injured myocardium of mice.
      Their precise location was determined with high-resolution MRI and compared with
      histological tissue sections, stained with Prussian blue for iron content. These
      experiments showed that iron nanoparticle-loaded cells could be identified at
      high resolution in the mouse heart. However, ischemic myocardium (after
      cryoinjury or left coronary artery ligation) was characterized by a signal
      attenuation similar to that induced by USPIO-labeled cells in T2*-weighted MR
      images, making detection of labeled stem cells in this area by T2*-sensitive
      contrast rather difficult. In animals with myocardial injury only, the signal
      attenuated areas were of the same size in proton density- and T2*-weighted MR
      images. In injured animals also receiving labeled cells the lesioned area
      appeared larger in T2*--than in proton density-weighted MR images. This sequence
      dependent lesion size change is due to the increased signal loss caused by the
      iron oxide nanoparticles, most sensitively detectable in the T2*-sensitive
      images. Thus, using the novel combination of these two parameter weightings,
      USPIO-labeled cells can be detected at high resolution in ischemic myocardium.

PMID- 15948225
TI  - Anti-microbial activity and film characterization of thiazolidinone derivatives
      of chitosan.
AB  - Thiazolidinone derivatives (TDCs) were prepared by converting chitosan into
      chitosan's Schiff's bases (CSBs), followed by treatment with mercaptoacetic acid.
      Both CSBs and TDCs were tested for antimicrobial activity against four different
      bacteria. All TDCs showed comparatively better anti-microbial activity without
      much affecting basic physical properties of chitosan such as film-forming
      capacity, tensile strength, etc. This indicates that chitosan derivatives with a
      thiazolidinone moiety might be a better material for wound dressing.

PMID- 15948226
TI  - Biosynthesis of an elastin-mimetic polypeptide with two different chemical
      functional groups within the repetitive elastin fragment.
AB  - A new protein engineering strategy was utilized to synthesize an elastin-mimetic
      polypeptide. The primary structure represents an elastic motif composed of thirty
      amino acids with one lysine and one glutamic acid per repeat unit EMM = (VPGVG
      VPGKG VGPVG VPGVG VPGEG VPGIG). The gene was constructed using a Seamless Cloning
      method by generating three DNA cassettes which all encoded the EMM repeat unit,
      but with different flanking restriction recognition sites. The DNA cassettes were
      assembled to yield a gene that could be directly cloned into the multiple cloning
      site of pBluescript II SK+. The resulting gene (EMM)(7) with approximately 650
      base pairs in length was further cloned into the expression vector pET-28b.
      Protein biosynthesis in E. coli strain BLR(DE3) resulted in the 21.5 kDa
      repeating polypeptide His(6)-(EMM)(7) yielding up to 50 mg . L(-1) of cell
      culture. Secondary structure analysis by far UV circular dichroism revealed a
      minimum at 197 nm and a shoulder at 218 nm indicative for a random coil with some
      type II beta-turn conformation content. Lower critical solution temperature
      (LCST) behavior strongly depends on salt and polypeptide concentration.
      Importantly, first cross-linking experiments indicate successful hydrogel
      formation with a surface structure reminiscent to natural elastin as visualized
      by SEM micrographs.

PMID- 15948227
TI  - Synthesis of and structural studies on repeating sequences of abductin.
AB  - Little data exist on the structure and function of compressible elastomeric
      proteins such as abductin. An understanding of the underlying structural features
      of these proteins may lead to the development of a new class of highly tailored
      "compressible" hydrogels. To that effect, in this work, the structure of abductin
      was investigated by means of studies on several synthetic peptides corresponding
      to the most frequent sequences of abductin. In particular, the 10 amino acid
      abductin peptide sequence FGGMGGGNAG, tandem repeated in the protein, and two
      related 25 and 40 amino acid polypeptides were synthesized. These peptides were
      studied with regard to secondary structure, self-assembly, and polymer
      morphology. The results obtained with these peptides allow us to propose a
      preliminary structure-elasticity relationship for abductin not dissimilar from
      that currently accepted for elastin.A possible mechanism of elasticity relating
      abductin to elastin.

PMID- 15948228
TI  - Folate receptor-mediated gene delivery using folate-poly(ethylene glycol)-poly(L
      lysine) conjugate.
AB  - For efficient receptor-mediated gene transfection, a new and simple formulation
      method based on using PEI and FOLPEGPLL conjugate was presented. Luciferase
      plasmid DNA and PEI were complexed to form slightly positive-charged
      nanoparticles, onto which FOL-PEG-PLL conjugate was surface coated. With
      increasing the coating amount of FOL-PEG-PLL conjugate, the FOL-PEG-PLL/PEI/DNA
      complexes exhibited increased surface zeta-potential values with concomitantly
      increased diameters, indicating that the PLL part was physically anchored on the
      surface of preformed PEI/DNA complexes with FOL moieties being exposed on the
      outside. The formulated complexes exhibited a considerably higher transfection
      efficiency against FOL receptor over-expressing KB cells than FOL receptor
      deficient A549 cells. This was caused by an enhanced cellular uptake of the
      resultant complexes via a receptor-mediated endocytosis process. The formulated
      complexes showed a higher gene expression level, even in the presence of serum,
      than the PEI/DNA or Lipofectamine/DNA complexes. This was attributed to the PEG
      chains present on the surface of complexes that could work as a protective shield
      layer against aggregation caused by non-specific protein adsorption. The FOL-PEG
      PLL/PEI/DNA complexes also demonstrated better cell viability than the PEI/DNA
      complexes.(1)H NMR spectrum of FOL-PEG-PLL conjugate.

PMID- 15948229
TI  - Ionic liquids as reaction medium in cellulose functionalization.
AB  - The application of different ionic liquids (IL), namely 1-N-butyl-3
      methylimidazolium chloride ([C(4)mim](+)Cl(-)), 3-methyl-N-butyl-pyridinium
      chloride and benzyldimethyl(tetradecyl)ammonium chloride were investigated as
      solvents for cellulose. The ILs used have the ability to dissolve cellulose with
      a degree of polymerization in the range from 290 to 1 200 to a very high
      concentration. Using [C(4)mim](+)Cl(-), no degradation of the polymer appears. By
      (13)C NMR measurement it was confirmed that this IL is a so-called non
      derivatizing solvent. [C(4)mim](+)Cl(-) can be applied as a reaction medium for
      the synthesis of carboxymethyl cellulose and cellulose acetate. Without using any
      catalyst, cellulose derivatives with high degree of substitution could be
      prepared.(13)C NMR spectrum of cellulose dissolved in the IL [C(4)mim](+)Cl(-)
      (top). The (13)C NMR spectrum of cellulose dissolved in DMSO/tetrabutylammonium
      fluoride trihydrate is shown for comparison (bottom).

PMID- 15948230
TI  - New enantiomeric polylactide-block-poly(butylene succinate)-block-polylactides:
      syntheses, characterization and in situ self-assembly.
AB  - In situ self-assemblies of new biodegradable triblock PLLA-b-PBS-b-PLLA and PDLA
      b-PBS-b-PDLA have been investigated in acetonitrile solution. At first, two
      series of PLLA-b-PBS-b-PLLA and PDLA-b-PBS-b-PDLA, respectively denoted as the P
      and Q triblock copolyester series, were prepared with fixed PBS block ((overline)
      M(n,NMR) = 6.9 kDa) and diverse enantiomeric PLLA/PDLA blocks. Further, their
      chemical structures and thermal properties were characterized by means of
      titration, nuclear magnetic resonance spectroscopy (NMR), gel permeation
      chromatography (GPC), polarimeter, wide-angle X-ray diffraction (WAXD) and
      thermal analytical instruments. When mixing the synthesized enantiomeric
      copolyester pairs denoted as P(1)/Q(1) - P(8)/Q(8) in acetonitrile solution at 60
      degrees C, in situ self-assemblies were found to happen for the P(4)/Q(4) to
      P(8)/Q(8) pairs, bearing longer enantiomeric PLA block lengths. DSC and WAXD
      analysis of the self-assembled microparticles demonstrated that PLLA/PDLA racemic
      crystals were formed for the P(5)/Q(5) - P(8)/Q(8) systems, as evidenced by their
      melting points over 200 degrees C, and a new X-ray diffraction peak detected at
      2theta = 11.8 degrees . Moreover, morphological studies by scanning electron
      microscopy (SEM) indicated the formation of disk- or platelet-like
      microparticles. It was noted that the diameters of the microparticles self
      assembled in situ decreased from 1.28-1.50 mum down to 480-660 nm, through
      tailoring the enantiomeric PLA block length. Other factors, such as a central PBS
      block, the enantiomeric block length and the preparation conditions were
      suggested to play important roles in the in situ self-assembly of these
      enantiomeric triblock copolyesters. These results provide a facile way to self
      assemble hydrophobic, biodegradable microparticles, through tuning the important
      van der Waals stereocomplexation interactions between two enantiomeric blocks in
      solution.

PMID- 15948231
TI  - Water-soluble nanoparticles from random copolymer and oppositely charged
      surfactant, 3a. Nanoparticles of poly(ethylene glycol)-based cationic random
      copolymer and fatty acid salts.
AB  - In this report, we investigate the nanoparticle formation between random
      copolymers (RCPs) of methoxy-poly(ethylene glycol) monomethacrylate (MePEGMA) and
      (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) and oppositely
      charged natural surfactants, sodium oleate and sodium laurate, using
      turbidimetric titration, steady-state fluorescence, dynamic light scattering, and
      electron microscopy. Though sodium oleate and sodium laurate are sparingly
      soluble in water, the nanoparticle complexes formed between the RCPs and these
      surfactants are soluble in the entire range of compositions studied here,
      including the stoichiometric electronetural complexes. The spherical nature of
      these nanoparticle complexes is revealed by electron microscopic (EM) analysis.
      Dynamic light scattering (DLS) showed that the average diameters of the
      nanoparticles are in the range 50 to 150 nm, which is supported by EM analysis.
      Pyrene fluorescence experiments suggested that these soluble nanoparticles have
      hydrophobic cores, which may solubilize hydrophobic drug molecules. The polarity
      index (I(1)/I(3)) obtained from the pyrene fluorescence spectra and the
      conductometric measurements showed that the critical concentration of fatty acid
      salts needed to obtain nanoparticles are in the order of 10(-4) M. Further, the
      complexation of such poorly water-soluble amphiphilic surfactants with polymers
      offers a useful method for the immobilization of hydrophobic compounds towards
      water-soluble drug carrier formulations. The formation of water-soluble
      nanoparticles by the self-assembly of fatty acid salts upon interacting with
      oppositely charged poly(ethylene glycol)-based polyions.

PMID- 15948232
TI  - Interpretation of butyltin mass spectra using isotope pattern reconstruction for
      the accurate measurement of isotope ratios from molecular clusters.
AB  - The fragmentation patterns of butyltin compounds (mono-, di-, and tributyltin) in
      an electron impact ion source were studied using an isotope pattern
      reconstruction algorithm with emphasis on isotope ratio measurements from
      molecular clusters. For this purpose, standards of natural tin isotope abundance
      and a (119)Sn-enriched mixture of the three compounds were both ethylated and
      propylated using sodium tetraalkylborates. The corresponding mass spectra of the
      various tetraalkyltin compounds prepared were obtained by GC/MS after their
      extraction with hexane. The results showed that pure interference-free molecular
      clusters were obtained only for certain R(3)Sn(+) ions where no isobaric overlap
      with R(2)SnH(+) ions occurred (e.g. BuEt(2)Sn(+) overlaps with Bu(2)SnH(+)).
      These ions are ideal candidates for accurate Sn isotope ratio measurements, while
      isotope pattern perturbing interferences are observed for other molecular
      fragments down to Sn(.)(+). Isotope pattern reconstruction algorithm thus can be
      used as an analytical tool to ensure the absence of molecular interferences--a
      requirement for accurate isotope ratio measurements from molecular clusters. The
      relevance of these studies for the determination of butyltin compounds in
      environmental samples by isotope dilution GC/MS is also discussed.

PMID- 15948233
TI  - MR properties of excised neural tissue following experimentally induced
      demyelination.
AB  - Changes in the magnetic resonance (MR) parameters of demyelinated neural tissue
      were measured in vitro using an experimental animal model. A tellurium (Te) diet
      was applied to weanling rats to induce the demyelination process in the sciatic
      nerve. The quantitative MR parameters, such as T(1), T(2) relaxation time
      constants and magnetization transfer (MT) were measured each day after applying
      the Te diet (up to 7 days) and were found to be substantially different from
      those of normal nerves. An increase in the average T(1) and T(2) was observed
      along with a decrease in the MT ratio (MTR) and the quantitative MT parameter
      M(0B), which describes the semisolid pool of protons. Most of the MR parameters
      correlated very well with the myelin fraction of neural tissue evaluated by
      quantitative histopathology. The T(2) relaxation spectrum provided the most
      efficient quantitative assessment of changes in neural tissue microstructure and
      its analysis resulted in a powerful tool to distinguish the processes of
      demyelination and inflammation. In comparison, the MT measurements were less
      successful.

PMID- 15948234
TI  - Inhibitory effect of adeno-associated virus-mediated gene transfer of human
      endostatin on hepatocellular carcinoma.
AB  - AIM: To investigate the effect of adeno-associated virus-mediated gene transfer
      of human endostatin on the growth of hepatocellular carcinoma (HCC). METHODS: HCC
      cell line Hep3B was infected with recombinant adeno-associated virus containing
      human endostatin gene (rAAV2-hEndo). The results of transfection were detected by
      RT-PCR and SDS-PAGE assay. MTT assay was used to observe the effects of
      supernatant of transfected cells on ECV304 cell proliferation. An animal model of
      HCC was established by injecting Hep3B cells subcutaneously into the back of nude
      mice. Intratumoral injection of rAAV2-hEndo, empty virus and phosphate-buffered
      saline were given sequentially. Serum endostatin was determined by ELISA, the
      inhibitory effect of endostatin on the growth of xenograft was assessed in 3 wk.
      RESULTS: The results of RT-PCR and SDS-PAGE assay confirmed that rAAV2-hEndo
      successfully transfected Hep3B cells, and endostatin was secreted from Hep3B
      cells to medium. The supernatant of transfected cells markedly inhibited the
      proliferation of ECV304 cells (P<0.01). Intratumoral injection of rAAV2-hEndo (2
      x 10(10) v.g.) led to a sustained serum endostatin level of approximately
      (86.71+/-5.19) ng/mL. The tumor volume and microvessel density were less in rAAV2
      hEndo group than in control groups (P<0.01). CONCLUSION: Human endostatin can be
      stably expressed by adeno-associated virus-mediated gene transfer and effectively
      inhibit the growth of HCC.

PMID- 15948235
TI  - Nude mice multi-drug resistance model of orthotopic transplantation of liver
      neoplasm and Tc-99m MIBI SPECT on p-glycoprotein.
AB  - AIM: To establish a model of drug-resistant neoplasms using a nude mice model,
      orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy.
      METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected
      subdermally to form the tumor-supplying mice. The orthotopic drug-resistant
      tumors were formed by implanting the tumor bits under the envelope of the mice
      liver and induced by abdominal chemotherapy with Pharmorubicin. Physical
      examination, ultrasonography, spiral CT and visual inspection were used to
      examine tumor progression. RT-PCR and immunohistochemistry were used to detect
      expression of mdr1 mRNA and its encoded protein p-glycoprotein (p-gp). Tc-99m
      sestamibi scintigraphy was performed by obtaining planar abdominal images at 20
      min after injection, and the liver/heart ratios were calculated. RESULTS: Post
      implantation mortality was 0% (0/25), tumor implantation success was 90% (22/25),
      and the rate of implanting successfully for the second time was 100% (3/3). Tumor
      induction using Pharmorubicin was 80% (16/20). The mdr1 mRNA expression of the
      induced group was 23 times higher than that of the control group, and p-gp
      protein expression was 13-fold higher compared to the control group. The
      liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased
      significantly in the induced group as compared to the control group. CONCLUSION:
      We have established an in vivo model of mdr1 in nude mice by orthotopic
      transplantation of liver neoplasm coupled to chemotherapy. We propose that
      identification of drug resistance as characterized by decreased 99mTc-ppm
      radiography due to enhanced clearance by p-gp may be useful in detecting in vivo
      drug resistance, as well as a useful tool in designing more effective therapies.

PMID- 15948236
TI  - CIK cells from patients with HCC possess strong cytotoxicity to multidrug
      resistant cell line Bel-7402/R.
AB  - AIM: To investigate the cytotoxicity of the cytokine-induced killer (CIK) cells
      from the post-operation patients with primary hepatocellular carcinoma (HCC) to
      multidrug-resistant (MDR) cell of HCC both in vitro and in vivo. METHODS: A drug
      resistant cell line was established by culturing human HCC cell line Bel-7402 in
      complete RPMI 1640 medium with increasing concentrations of adriamycin from 10 to
      2,000 nmol/L. CIK cells were obtained by inducing the peripheral blood
      mononuclear cells with rhIFN-gamma, monoclonal anti-CD3 antibody, rhIL-1alpha as
      well as rhIL-2, which were added into the culture. To detect the cytotoxicity of
      the CIK cells from HCC patients, the Bel-7402/R was taken as target (T) cells and
      CIK cells as effect (E) cells. Cytotoxic test was performed and measured by MTT.
      As to in vivo test, CIK cells were transfused into patients with HCC. The tumor
      specimens of the patients were obtained and immunohistochemistry was carried out
      to detect CD3, CD45, CD45RO as well as CD68. RESULTS: A MDR 1 HCC cell line Bel
      7402/R was established. Its MDR1 mRNA overexpressed which was shown by RT-PCR;
      the P-glycoprotein expression increased from 1.32% of parent cells to 54%. CIK
      cells expanded vigorously by more than 70-fold and the CD3+CD56+ increased by
      more than 600-fold after 3-wk incubation on average. The cytotoxicity of CIK from
      HCC patients to Bel-7402/R was about 50% and to L-02 below 10% (t = 8.87,
      P<0.01), the same as that of CIK from normal individuals. Each of the 17 patients
      received 1-5 x 10(10) of CIK cell transfusion. No side effects were observed.
      After CIK treatment, the tumor tissue nodules formed and a large amount of
      lymphocytes infiltrated in the liver cancer tissue and CD3, CD45, CD45RO, and
      CD68 increased greatly which was shown by immunohistochemistry. CONCLUSION: A
      stable MDR1 HCC cell line has been established which could recover from liquid
      nitrogen and CIK from HCC patients has strong cytotoxicity to MDR HCC cell. CIK
      adoptive immunotherapy is safe and has no side effects. Receivers improved their
      immunity to tumor evidently. CIK treatment may be a better choice for HCC
      patients after operation to prevent the recurrence, especially when tumors have
      developed drug resistance.

PMID- 15948237
TI  - Effect of lamivudine in HBeAg-positive chronic hepatitis B: discordant effect on
      HBeAg and HBV DNA according to pretreatment ALT level.
AB  - AIM: To clarify differences in antiviral effect of the drug in patients with
      different ALT levels, we examined the changes in HBV markers in patients with
      high or low ALT levels with or without lamivudine treatment. METHODS: Thirty
      seven HBeAg-positive patients were studied. Ten patients with ALT levels higher
      than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were
      treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with
      ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4)
      were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined
      monthly for 11.9+/-0.4 mo. RESULTS: The ALT level normalized in all 10 patients
      of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo
      (groups 1 vs 2, P = NS; groups 1 vs 3, P = 0.002; groups 1 vs 4, P<0.0001). HBV
      DNA fell below the detection limit in all 10 patients of group 1, 7/8 of group 2,
      0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P = NS). HBeAg
      became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3,
      and 0/10 of group 4 within 12 mo (groups 1 vs 2, P = 0.02; groups 1 vs 3, P =
      NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT
      levels can be considered good candidates for lamivudine therapy, probably because
      lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV
      DNA loss, in these patients.

PMID- 15948238
TI  - Genes transactivated by hepatitis C virus core protein, a microarray assay.
AB  - AIM: To explore the new target genes transactivated by hepatitis C virus (HCV)
      core protein and to elucidate the pathogenesis of HCV infection. METHODS: Reverse
      transcribed cDNA was subjected to microarray assay. The coding gene
      transactivated by HCV core protein was cloned and analyzed with bioinformatics
      methods. RESULTS: The expressive vector of pcDNA3.1(-)-core was constructed and
      confirmed by restriction enzyme digestion and DNA sequencing and approved
      correct. mRNA was purified from HepG2 and HepG2 cells transfected with pcDNA3.1(
      )-core, respectively. The cDNA derived was subjected to microarray assay. A new
      gene named HCTP4 was cloned with molecular biological method in combination with
      bioinformatics method. CONCLUSION: HCV core is a potential transactivator.
      Microarray is an efficient and convenient method for analysis of differentially
      expressed genes.

PMID- 15948239
TI  - Correlation of serum leptin levels with anthropometric and metabolic parameters
      and biochemical liver function in Chinese patients with chronic hepatitis C virus
      infection.
AB  - AIM: To determine serum leptin levels and investigate their correlations with
      anthropometric and metabolic parameters and biochemical liver function in
      patients with chronic hepatitis C virus (HCV) infection and their potential
      clinical implications. METHODS: Forty-two chronic HCV-infected patients without
      anti-viral treatment were enrolled in this study, 30 patients had chronic
      hepatitis C, 10 had cirrhosis, and 2 had hepatocellular carcinoma (HCC). Thirty
      age- and sex-matched healthy individuals served as controls. Serum leptin levels
      were determined by ELISA. The biochemical liver function and serum lipids were
      determined at the same time. The height and body weight of patients and controls
      were measured, and body mass index (BMI) and body fat were calculated
      simultaneously. The correlations of serum leptin levels with anthropometric and
      metabolic parameters and biochemical liver function were assessed statistically.
      RESULTS: The mean of serum leptin levels in patients with chronic hepatitis C,
      HCV-associated cirrhosis, HCV-associated HCC and control groups was (6.13+/
      3.94), (5.25+/-4.21), (4.17+/-0.28), and (3.59+/-3.44) ng/mL, respectively. The
      serum leptin level in patients with chronic hepatitis C was significantly higher
      than that in controls. The serum leptin levels between cirrhotic patients and
      controls and between male and female cirrhotic patients had no significant
      difference. Serum leptin levels were positively-correlated with body fat, BMI,
      and apolipoprotein B (Apo B) in patients with chronic HCV infection. The serum
      alanine aminotransferase (ALT) levels were closely-correlated with BMI in
      patients with chronic hepatitis C. CONCLUSION: HCV infection interferes with fat
      and lipid metabolism in patients with chronic HCV infection and leptin may play a
      role in hepatosteatosis.

PMID- 15948240
TI  - Expression and immunoreactivity of an epitope of HCV in a foreign epitope
      presenting system.
AB  - AIM: To construct and highly express an epitope of hepatitis C virus (HCV) in a
      foreign epitope presenting vector based on an insect virus, and to study the
      antigenicity of the epitope. METHODS: The HCV epitope sequence (amino acid
      residues 315 to 328: EGHRMAWDMMMNWS) of the E1 region was constructed at
      different positions of a foreign epitope presenting vector based on an insect
      virus, flock house virus (FHV) capsid protein encoding gene as a vector, and
      expressed in E. coli cells. Western blotting and ELISA were used to detect the
      immunoreactivity of these recombinant proteins. RESULTS: The gene encoding of the
      concerned B-cell epitope of HCV E1 envelope protein was expressed on FHV capsid
      carrier protein at positions I1 (aa 106), I2 (aa 153) and I3 (aa 305),
      respectively, on the surface of FHV capsid protein. The recombinant proteins in
      this system could be highly expressed in more than 40% of total cell protein of
      E. coli BL21. All the expressed recombinant proteins were in inclusion body form,
      and showed obvious immunoreactivity by Western blotting. Further purified
      recombinant proteins were detected by indirect ELISA as coating antigen
      respectively. All recombinant proteins could still show immunoreactivity.
      CONCLUSION: The epitope of HCV E1 envelope protein can be highly expressed in FHV
      carrier system as a chimeric protein with high immunoreactivity. This system has
      multiple entry sites conferring many possible conformations closer to the native
      one for a given sequence.

PMID- 15948241
TI  - Green tea polyphenol epigallocatechin-3-gallate blocks PDGF-induced proliferation
      and migration of rat pancreatic stellate cells.
AB  - AIM: To clarify the effects of epigallocatechin-3-gallate (EGCG) on the platelet
      derived growth factor (PDGF)-BB-induced proliferation and migration of pancreatic
      stellate cells (PSCs). METHODS: PSCs were isolated from rat pancreas tissue and
      used in their culture-activated, myofibroblast-like phenotype. Cell proliferation
      was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine. Cell
      migration was assessed using modified Boyden chambers. Cyclin D1, p21Waf1, and
      p27Kip1 expression and phosphorylation of PDGF beta-receptor, extracellular
      signal-regulated kinase, and Akt were examined by Western blotting. Activation of
      phospha-tidylinositol 3-kinase was examined by kinase assay using
      phosphatidylinositol as a substrate. Cell cycle was assessed by flow cytometry
      after staining with propidium iodide. RESULTS: EGCG at non-cytotoxic
      concentrations inhibited PDGF-induced proliferation and migration. This effect
      was associated with the inhibition of cell cycle progression beyond the G1 phase,
      decreased cyclin D1 and increased p27Kip1 expression. EGCG inhibited tyrosine
      phosphorylation of PDGF beta-receptor and downstream activation of extracellular
      signal-regulated kinase and phosphatidylinositol 3-kinase/Akt pathways.
      CONCLUSION: EGCG inhibited PDGF-BB-induced proliferation and migration of PSCs
      through the inhibition of PDGF-mediated signaling pathways.

PMID- 15948242
TI  - Different cytokine response of primary colonic epithelial cells to commensal
      bacteria.
AB  - AIM: To determine if primary murine colonic epithelial cells (CEC) respond to
      commensal bacteria and discriminate between different types of bacteria. METHODS:
      A novel CEC: bacteria co-culture system was used to compare the ability of the
      colonic commensal bacteria, Bacteroides ovatus, E. coli (SLF) and Lactobacillus
      rhamnosus (LGG) to modulate production of different cytokines (n = 15) by primary
      CEC. Antibody staining and flow cytometry were used to investigate Toll-like
      receptor (TLR) expression by CEC directly ex vivo and TLR responsiveness was
      determined by examining the ability of TLR ligands to influence CEC cytokine
      production. RESULTS: Primary CEC constitutively expressed functional TLR2 and
      TLR4. Cultured in complete medium alone, CEC secreted IL-6, MCP-1 and IP-10 the
      levels of which were significantly increased upon addition of the TLR ligands
      peptidoglycan (PGN) and lipopolysaccharide (LPS). Exposure to the commensal
      bacteria induced or up-regulated different patterns of cytokine production and
      secretion. E. coli induced production of MIP-1alpha/beta and betadefensin3
      whereas B. ovatus and L. rhamnosus exclusively induced MCP-1 and MIP-2alpha
      expression, respectively. TNFalpha, RANTES and MEC were induced or up-regulated
      in response to some but not all of the bacteria whereas ENA78 and IP-10 were up
      regulated in response to all bacteria. Evidence of bacterial interference and
      suppression of cytokine production was obtained from mixed bacterial: CEC co
      cultures. Probiotic LGG suppressed E. coli- and B. ovatus-induced cytokine mRNA
      accumulation and protein secretion. CONCLUSION: These observations demonstrate
      the ability of primary CEC to respond to and discriminate between different
      strains of commensal bacteria and identify a mechanism by which probiotic
      bacteria (LGG) may exert anti-inflammatory effects in vivo.

PMID- 15948243
TI  - Activation of JAK-STAT pathway is required for platelet-derived growth factor
      induced proliferation of pancreatic stellate cells.
AB  - AIM: To clarify the role of Janus kinase-signal transducers and activators of
      transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced
      proliferation in activated pancreatic stellate cells (PSCs). METHODS: PSCs were
      isolated from rat pancreas tissue, and used in their culture-activated,
      myofibroblast-like phenotype. STAT-specific binding activity was assessed by
      electrophoretic mobility shift assay. Activation of Src, JAK2, STAT1, STAT3, and
      ERK was determined by Western blotting using anti-phospho-specific antibodies.
      Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'
      deoxyuridine. RESULTS: PDGF-BB induced STAT-specific binding activity, and
      activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at
      clinically relevant concentrations decreased basal activation of JAK2 and STAT3.
      PDGF-induced activation of STAT1 and STAT3 was inhibited by a Src inhibitor PP1
      and a JAK2 inhibitor AG490, whereas PDGF-induced activation of ERK was inhibited
      by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and
      AG490 as well as by STAT3 antisense oligonucleotide. CONCLUSION: PDGF-BB
      activated JAK2-STAT pathway via Src-dependent mechanism. Activation of JAK2-STAT3
      pathway, in addition to ERK, may play a role in PDGF-induced proliferation of
      PSCs.

PMID- 15948244
TI  - Establishment and characterization of an opisthorchiasis-associated
      cholangiocarcinoma cell line (KKU-100).
AB  - AIM: To establish and characterize a new cholangiocarcinoma cell line from a
      patient living in the Opisthorchis viverrini (O. viverrini) endemic area of
      Northeast Thailand. METHODS: Fresh liver biopsy and bile specimens were obtained
      from a 65-year-old Thai woman with cholangiocarcinoma of the porta hepatis. After
      digestion, the cells were cultured in Ham's F12 media. The established cell line
      was then characterized for growth kinetics, cell morphology, imm-unocytochemistry
      and cytogenetics. Tumorigenicity of the cell line was determined by
      heterotransplanting in nude mice. RESULTS: The primary tumor was a poorly
      differentiated tubular adenocarcinoma. Examination of the bile revealed malignant
      cells with O. viverrini eggs. The cholangioc-arcinoma cell line KKU-100 was
      established 4 mo after the primary culture-population doubling time was 72 h. KKU
      100 possesses compact and polygonal-shaped epithelial cells.
      Immunocytochemically, this cell line exhibited cytokeratin, EMA, CEA, and CA125,
      but not alpha-fetoprotein (AFP), CA19-9, desmin, c-met, or p53. Such protein
      expressions parallel those of the primary tumor. Cytogenetic analysis identified
      aneuploidy karyotypes with a modal chromosome number of 78 and marked chromosomal
      structural changes. Inoculation of KKU-100 cells into nude mice produced a
      transplantable, poorly differentiated aden-ocarcinoma, similar to the original
      tumor. CONCLUSION: KKU-100 is the first egg-proven, Opisthorchis-associated
      cholangiocarcinoma cell line, which should prove useful for further
      investigations of the tumor biology of this cancer.

PMID- 15948245
TI  - Lethal effect and apoptotic DNA fragmentation in response of D-GalN-treated mice
      to bacterial LPS can be suppressed by pre-exposure to minute amount of bacterial
      LPS: dual role of TNF receptor 1.
AB  - AIM: To investigate whether induction of tolerance of mice to lipopolysaccharide
      (LPS) was able to inhibit apoptotic reaction in terms of characteristic DNA
      fragmentation and protect mice from lethal effect. METHODS: Experimental groups
      of mice were pretreated with non-lethal amount of LPS (0.05 microg). Both control
      and experimental groups simultaneously were challenged with LPS plus D-GalN for 6
      7 h. The evaluations of both DNA fragmentations from the livers and the
      protection efficacy against lethality to mice through induction of tolerance to
      LPS were conducted. RESULTS: In the naive mice challenge with LPS plus D-GalN
      resulted in complete death in 24 h, whereas a characteristic apoptotic DNA
      fragmentation was exclusively seen in the livers of mice receiving LPS in
      combination with D-GalN. The mortality in the affected mice was closely
      correlated to the onset of DNA fragmentation. By contrast, in the mice pre
      exposed to LPS, both lethal effect and apoptotic DNA fragmentation were
      suppressed when challenged with LPS/D-GalN. In addition to LPS, the induction of
      mouse tolerance to TNF also enabled mice to cross-react against death and
      apoptotic DNA fragmentation when challenged with TNF and/or LPS in the presence
      of D-GalN. Moreover, this protection effect by LPS could last up to 24 h. TNFR1
      rather than TNFR2 played a dual role in signaling pathway of either induction of
      tolerance to LPS for the protection of mice from mortality or inducing morbidity
      leading to the death of mice. CONCLUSION: The mortality of D-GalN-treated mice in
      response to LPS was exceedingly correlated to the onset of apoptosis in the
      liver, which can be effectively suppressed by brief exposure of mice to a minute
      amount of LPS. The induced tolerance status was mediated not only by LPS but also
      by TNF. The developed tolerance to either LPS or TNF can be reciprocally cross
      reacted between LPS and TNF challenges, whereas the signaling of induction of
      tolerance and promotion of apoptosis was through TNFR1, rather than TNFR2.

PMID- 15948246
TI  - Cholecystokinin octapeptide improves cardiac function by activating
      cholecystokinin octapeptide receptor in endotoxic shock rats.
AB  - AIM: To explore the effect of sulfated cholecystokinin octapeptide (sCCK-8) on
      cardiac functions and its receptor mechanism in endotoxic shock (ES) rats.
      METHODS: The changes of the mean arterial pressure (MAP), heart rate (HR), the
      left ventricular pressure (LVP) and the maximal/minimum rate of LVP (+/
      LVdp/dt(max))) were measured by using physiological record instrument in eight
      groups of rats. The expression of cholecystokinin-A receptor (CCK-AR) and
      cholecystokinin-B receptor (CCK-BR) mRNA of myocardium in ES rats was examined by
      reverse transcription polymerase chain reaction (RT-PCR). RESULTS: (1) Low doses
      of sCCK-8 (0.4 microg/kg) caused tachycardia (441+/-27, normal control 391+/-22
      s/min) and slight increase in MAP, LVP and +/-LVdp/dt(max) (16.96+/-1.79, 18.21+/
      1.69 and +768.85+/-31.28/-565.04+/-27.71 kPa, respectively, all P<0.01), while
      medium doses (4.0 microg/kg) and high doses of sCCK-8 (40 microg/kg) elicited
      bradycardia and marked increase in MAP, LVP and +/-LVdp/dt(max) (17.29+/-1.63,
      19.46+/-2.57 and +831.46+/-22.57/-606.08 +/-31.32; 17.46+/-1.08, 19.83+/-2.91 and
      +914.52+/-35.95/-639.15+/-30.23 kPa, respectively, all P<0.01). Proglumide (1.0
      mg/kg), a nonselective antagonist of CCK-receptor (CCK-R), significantly
      inhibited the pressor effects of sCCK-8 (15.96+/-1.38, 17.36+/-0.66 and +748.18+/
      19.29/-512.12+/-14.39 kPa, respectively, all P<0.01), whilst reversing the
      bradycardiac responses. (2) High doses of LPS (8 mg/kg) elicited marked decrease
      in MAP, LVP and +/-LVdp/dt(max). (7.16+/-0.59, 7.6+/-0.68 and +298.01+/-25.52/
      166.96+/-19.25 kPa, respectively, all P<0.01). Pretreatment with sCCK-8 (40
      microg/kg) could reverse the decline of cardiac functions (10.71+/-0.45, 11.7+/
      1.26 and +446.04+/-67.18/-347.90+/-36.98 kPa, respectively, all P<0.01), while
      proglumide could cause further decline of cardiac function in ES rats (4.71+/
      0.67, 5.58+/-1.25 and +226.48+/-15.84/-142.83+/-20.23 kPa, respectively, all
      P<0.01). (3) CCK-A/BR mRNAs were expressed in myocardium of control rats. Gene
      expression of CCK-AR and CCK-BR significantly increased in myocardium of ES rats.
      The increase of CCK-AR mRNA induced by LPS began at 0.5 h, peaked at 2 h, kept a
      high level at 6 h and declined at 12 h, respectively. Similar to CCK-AR mRNA, the
      expression of CCK-BR mRNA peaked at 2 h and kept a high level at 6 h, but it did
      not change at the first 0.5 h and was stable at a high level at 12 h. CONCLUSION:
      The above results indicate that endogenous and exogenous sCCK-8 may significantly
      improve cardiac function and intractable hypotension of ES rats, which was likely
      related to high expression of CCK-A/BR in myocardium induced by LPS.

PMID- 15948247
TI  - Construction of a novel Shigella live-vector strain co-expressing CS3 and LTB/STm
      of enterotoxigenic E.coli.
AB  - AIM: To construct and evaluate a polyvalent recombinant vaccine strain Shigella
      flexneri 2a T32 against enterotoxigenic E.coli (ETEC). METHODS: By using a host
      plasmid balanced lethal system based on asd gene, a polyvalent recombinant strain
      was constructed to highly express CS3 and regularly express fusion enterotoxin of
      LTB subunit and mutant ST (LTB/STm) in a vaccine strain Shigella flexneri 2a T32
      with specific deletion of asd gene. Fimbria CS3 was observed by
      immunofluorescence and electron microscopy assay. The security of LTB/STm was
      examined by ileal loop assay and suckling mouse assay. To evaluate this new
      candidate vaccine, it was compared with a previous vaccine strain in plasmid and
      protein level, growth assay and immunogenicity in Balb/c mice. RESULTS: The newly
      constructed vaccine expressed CS3 and grew better than the previously constructed
      vaccine except for the lower expression of LTB/STm. Serum IgG and mucosal IgA
      against CS3, LTB, ST, and host lipopolysaccharide (LPS) were produced after
      immunization of Balb/c mice by oral route with the new strain. The titers were
      not significantly different from the Balb/c mice with the previous strain.
      CONCLUSION: This novel candidate diarrheal vaccine can effectively induce serum
      and mucosal antibody responses against ETEC and Shigella.

PMID- 15948248
TI  - Intravenous acid fibroblast growth factor protects intestinal mucosal cells
      against ischemia-reperfusion injury via regulating Bcl-2/Bax expression.
AB  - AIM: To detect the effect of acid fibroblast growth factor (aFGF) on apoptosis
      and gene expression of bax and bcl-2 gene in rat intestine after
      ischemia/reperfusion (I/R) injury, and to explore the protective mechanisms of
      aFGF. METHODS: One hundred and eight Wistar rats were randomly divided into sham
      operated control group (C) (n = 6), intestinal ischemia group (I) (n = 6), aFGF
      treatment group (A) (n = 48) and intestinal ischemia-reperfusion group (R) (n =
      48). In group I, the animals were killed after 45 min of superior mesenteric
      artery (SMA) occlusion, while in groups R and A, the rats sustained 45 min of SMA
      occlusion and were then treated with normal saline and aFGF, respectively,
      sustained 15 min, 30 min, 1, 2, 6, 12, 24, or 48 h of reperfusion, respectively.
      In group C, SMA was separated, but without occlusion. Apoptosis in intestinal
      villus was determined with terminal deoxynucleotidyl transferase mediated dUTP
      biotin nick-end labeling technique (TUNEL). Intestinal tissue samples were taken
      not only for detection of bax and bcl-2 gene expression by RT-PCR, but also for
      detection of bax and bcl-2 protein expression and distribution by
      immunohistochemical analysis. RESULTS: The rat survival rates in aFGF treated
      group were higher than group R (P<0.05) and the improvement of intestinal
      histological structures was observed at 2, 6, and 12 h after the reperfusion in
      group A compared with group R. The apoptotic rates were (41.17+/-3.49)%, (42.83+/
      5.23)% and (53.33+/-6.92)% at 2, 6 and 12 h after reperfusion, respectively in
      group A, apparently less than those of group R at matched time points (50.67+/
      6.95, 54.17+/-7.86, 64.33+/-6.47, respectively) (P<0.05). The bax gene
      transcription and translation were significantly decreased in group A vs group R,
      while mRNA and protein contents of Bcl-2 in group A were obviously higher than
      those in group R during 2-12 h period after reperfusion. CONCLUSION: The changes
      in histological structure and the increment of apoptotic rate indicated that the
      intestinal barrier was damaged after intestinal I/R injury, whilst intravenous
      aFGF could alleviate apoptosis induced by ischemia and reperfusion in rat
      intestinal tissues, in which genes of bax and bcl-2 might play important roles.

PMID- 15948249
TI  - Adult islets cultured in collagen gel transdifferentiate into duct-like cells.
AB  - AIM: To establish a model of islet-ductal cell transdifferentiation to identify
      the transdifferentiated cells. METHODS: Collagen was extracted from rat tail at
      first. Purified rat islets were divided into three groups, embedded in collagen
      gel and incubated respectively in DMEM/F12 alone (control group), DMEM/F12 plus
      epidermal growth factor (EGF), DMEM/F12 plus EGF and cholera toxin (CT).
      Transdifferentiation was proved by microscopy, RT-PCR, immunohistochemistry and
      RIA. RESULTS: Islets embedded in collagen gel plus EGF and CT were cystically
      transformed and could express new gene cytokeratin 19 while still maintaining the
      expression of insulin and Pdx-1 genes. Immunohistochemistry demonstrated that the
      protein of cytokeratin 19 was only expressed in the third group. The insulin
      content secreted by islets in the third group decreased significantly during the
      transdifferentiation. CONCLUSION: CT is a crucial factor for the islet-ductal
      cell transdifferentiation.

PMID- 15948250
TI  - Bone marrow-derived mesenchymal stem cells protect against experimental liver
      fibrosis in rats.
AB  - AIM: Recent reports have shown the capacity of mesenchymal stem cells (MSCs) to
      differentiate into hepatocytes in vitro and in vivo. MSCs administration could
      repair injured liver, lung, or heart through reducing inflammation, collagen
      deposition, and remodeling. These results provide a clue to treatment of liver
      fibrosis. The aim of this study was to investigate the effect of infusion of bone
      marrow (BM)-derived MSCs on the experimental liver fibrosis in rats. METHODS:
      MSCs isolated from BM in male Fischer 344 rats were infused to female Wistar rats
      induced with carbon tetrachloride (CCl4) or dimethylnitrosamine (DMN). There were
      two random groups on the 42nd d of CCl4:CCl4/MSCs, to infuse a dose of MSCs
      alone; CCl4/saline, to infuse the same volume of saline as control. There were
      another three random groups after exposure to DMN: DMN10/MSCs, to infuse the same
      dose of MSCs on d 10; DMN10/saline, to infuse the same volume of saline on d 10;
      DMN20/MSCs, to infuse the same dose of MSCs on d 20. The morphological and
      behavioral changes of rats were monitored everyday. After 4-6 wk of MSCs
      administration, all rats were killed and fibrosis index were assessed by
      histopathology and radioimmunoassay. Smooth muscle alpha-actin (alpha-SMA) of
      liver were tested by immunohistochemistry and quantified by IBAS 2.5 software.
      Male rats sex determination region on the Y chromosome (sry) gene were explored
      by PCR. RESULTS: Compared to controls, infusion of MSCs reduced the mortality
      rates of incidence in CCl4-induced model (10% vs 20%) and in DMN-induced model
      (20-40% vs 90%). The amount of collagen deposition and alpha-SMA staining was
      about 40-50% lower in liver of rats with MSCs than that of rats without MSCs. The
      similar results were observed in fibrosis index. And the effect of the inhibition
      of fibrogenesis was greater in DMN10/MSCs than in DMN20/MSCs. The sry gene was
      positive in the liver of rats with MSCs treatment by PCR. CONCLUSION: MSCs
      treatment can protect against experimental liver fibrosis in CCl4-induced or DMN
      induced rats and the mechanisms of the anti-fibrosis by MSCs will be studied
      further.

PMID- 15948251
TI  - Gender differences in hepatic ischemic reperfusion injury in rats are associated
      with endothelial cell nitric oxide synthase-derived nitric oxide.
AB  - AIM: This study was designed to examine the hypothesis that gender differences in
      I/R injury are associated with endothelial cell nitric oxide synthase (eNOS)
      derived nitric oxide (NO). METHODS: Wistar rats were randomized into seven
      experimental groups (12 animals per group). Except for the sham operated groups,
      all rats were subjected to total liver ischemia for 40 min followed by
      reperfusion. All experimental groups received different treatments 45 min before
      the laparotomy. For each group, half of the animals (six) were used to
      investigate the survival; blood samples and liver tissues were obtained in the
      remaining six animals after 3 h of reperfusion to assess serum NO, alanine
      aminotransferase (ALT) and TNF-alpha levels, liver tissue malondialdehyde (MDA)
      content, and severity of hepatic I/R injury. RESULTS: Basal serum NO levels in
      female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS)
      group (66.7+/-11.0 micromol/L vs 45.3+/-10.1 micromol/L, P<0.01). Although serum
      NO levels decreased significantly after hepatic I/R (P<0.01, vs sham operated
      groups), they were still significantly higher in female rat (F) group than in
      male rat (M) group (47.8+/-8.6 micromol/L vs 23.8+/-4.7 micromol/L, P<0.01).
      Serum ALT and TNF-alpha levels, and liver tissue MDA content were significantly
      lower in F group than in M group (370.5+/-46.4 U/L, 0.99+/-0.11 microg/L and
      0.57+/-0.10 micromol/g vs 668.7+/-78.7 U/L, 1.71+/-0.18 microg/L and 0.86+/-0.11
      micromol/g, respectively, P<0.01). I/R induced significant injury to the liver
      both in M and F groups (P<0.01 vs sham operated groups). But the degree of
      hepatocyte injury was significantly milder in F group than in M group (P<0.05 and
      P<0.01). The median survival time was six days in F group and one day in M group.
      The overall survival rate was significantly higher in F group than in M group
      (P<0.05). When compared with male rats pretreated with saline (M group),
      pretreatment of male rats with 17-beta-estradiol (E2) (M+E2 group) significantly
      increased serum NO levels and significantly decreased serum ALT and TNF-alpha
      levels, and liver tissue MDA content after I/R (P<0.01). The degree of hepatocyte
      injury was significantly decreased and the overall survival rate was
      significantly improved in M+E2 group than in M group (P<0.01 and P<0.05). The NOS
      inhibitor N(w) -nitro-L-arginine methyl ester (L-NAME) treatment could completely
      abolish the protective effects of estrogen in both male and female rats.
      CONCLUSION: The protective effects afforded to female rats subjected to hepatic
      I/R are associated with eNOS-derived NO.

PMID- 15948252
TI  - Adenovirus-mediated FasL gene transfer into human gastric carcinoma.
AB  - AIM: To evaluate the possible value of FasL in gastric cancer gene therapy by
      investigating the effects of FasL expression on human gastric cancer cell line.
      METHODS: An adenoviral vector encoding the full-length human FasL cDNA was
      constructed and used to infect a human gastric cancer (SGC-7901) cell line. FasL
      expression was confirmed by X-gal staining, flow cytometric analysis and RT-PCR.
      The effect of FasL on cell proliferation was determined by clonogenic assay,
      cytotoxicity was detected by MTT assay, and cell viability was measured by trypan
      blue exclusion. The therapeutic efficiency of Ad-FasL in vivo was investigated
      with a xenograft tumor model in nude mice. RESULTS: SGC-7901 cells infected with
      Ad-FasL showed increased expression of FasL, resulting in significantly decreased
      cell growth and colony-forming activity when compared with control adenovirus
      infected cells. The cytotoxicity of anti-Fas antibody (CH-11) in gastric cancer
      cells was stronger than that of ActD (91+/-8 vs 60+/-5, P<0.01), and the
      cytotoxicity of Ad-FasL was stronger than that of CH-11 (60+/-5 vs 50+/-2,
      P<0.05). In addition, G1-phase arrest (67.75+/-0.39 vs 58.03+/-2.16, P<0.05) and
      apoptosis were observed in Ad-FasL-infected SGC-7901 cells, and the growth of SGC
      7901 xenografts in nude mice was retarded after intra-tumoral injection with Ad
      FasL (54% vs 0%, P<0.0001). CONCLUSION: Infection of human gastric carcinoma
      cells with Ad-FasL induces apoptosis, indicating that this target gene might be
      of potential value in gene therapy for gastric cancer.

PMID- 15948254
TI  - Applications of gray relational analysis in gastroenterology.
AB  - AIM: To introduce the basic methods of gray relational analysis (GRA) and to
      illustrate its applications in gastroenterology. METHODS: With the essential
      formulae of GRA and several typically practical examples, the procedure of GRA
      was introduced. Examples were drawn from the gastroenterological studies. Thus
      the trait of GRA could be demonstrated. RESULTS: The superiority of GRA in
      gastroenterological study was proved by the examples. CONCLUSION: GRA can be
      applied mechanically or flexibly in gastroenterology.

PMID- 15948253
TI  - Cell cycle arrest and apoptotic cell death in cultured human gastric carcinoma
      cells mediated by arsenic trioxide.
AB  - AIM: To investigate the effect of arsenic trioxide on human gastric cancer cell
      line MKN45 with respect to both cytotoxicity and induction of apoptosis in vitro.
      METHODS: MKN45 cells were treated with arsenic trioxide (As2O3) at the
      concentration of 1, 5, and 10 micromol/L, respectively, for three successive
      days. Cell growth and proliferation were observed by cell counting and trypan
      blue exclusion. Cytotoxicity of As2O3 was determined by MTT assay. Morphologic
      changes were studied with light microscopy. Flow cytometry was used to assay cell
      DNA distribution and apoptotic cells were confirmed with terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and DNA
      electrophoresis. RESULTS: The growth of MKN45 cells was significantly inhibited
      by As2O3 which was confirmed by colony-forming assay. After 7 d of culture with
      various concentrations of As2O3, colony-forming capacity of MKN45 cells decreased
      with As2O3 increment in comparison with that of control group. The inhibitory
      rate of colony-formation was 38.5%, 99.1%, and 99.5% when the concentration of
      As2O3 was 1, 5, and 10 micromol/L in culture medium, respectively. The cell
      number of a single colony in drug treatment groups was less than that of control
      group. The cell-killing rate of As2O3 to MKN45 cells was both dose- and time
      dependent with an IC50 of (11.05+/-0.25) micromol/L. After incubation in 10
      micromol/L As2O3 for 24 h, the cell-killing rate was 27.1%, and it was close to
      50% after 48 h. The results showed that As2O3 induced time- and dose-dependent
      apoptosis in MKN45 cells, blocked at G2/M phase. The apoptotic peak (sub-G1
      phase) appeared and cell apoptotic rate in MKN45 cells was 18.3-32.5% after
      treatment by 10 micromol/L As2O3 for 48 h. The percentage of G2/M cell of the
      experimental groups was 2.0-5.0 times than that of the control group. Gel
      electrophoresis of DNA from cells treated with each concentration of As2O3 for 48
      h revealed a "ladder" pattern, indicating preferential DNA degradation at the
      internucleosomal, linker DNA sections. TUNEL also demonstrated strand breaks in
      DNA of MKN45 cells treated with As2O3, while control cells showed negative
      labeling. CONCLUSION: As2O3 can induce apoptosis of human gastric carcinoma cells
      MKN45, which is the basis of its effectiveness. It shows great potential in the
      treatment of gastric carcinoma.

PMID- 15948255
TI  - Quality of gastric ulcer healing evaluated by endoscopic ultrasonography.
AB  - AIM: To evaluate the quality of gastric ulcer healing after different antiulcer
      treatment by endoscopic ultrasonography (EUS). METHODS: The patients were divided
      into three groups, and received lansoprazole, amoxicillin and clarithromycin for
      1 wk. Then group A took lansoprazole combined with tepreton for 5 wk, group B
      took lansoprazole and group C took tepreton for 5 wk. Endoscopy and EUS were
      performed before and 6 wk after medication. RESULTS: There was no significant
      difference in cumulative healing rate to S stage between the groups (89%, 82% vs
      83%, P>0.05). The rate of white scar formation was significantly higher in group
      A than in groups B and C (67%, 36%, 50%, P<0.05). The average contraction rates
      of the width of ulcer crater, length of disrupted muscularis propria layer and
      hypoechoic area were higher in group A than in groups B and C (0.792+/-0.090,
      0.660+/-0.105 vs 0.668+/-0.143, P<0.05). The hypoechoic area disappeared in four
      cases of group A, one of group B and two of group C. The percentage of hypoechoic
      area disappearance was higher in group A than in the other two groups (44%, 9% vs
      17%, P<0.05). Gastric ulcer healing was better in group A. CONCLUSION: The
      combined administration of proton-pump inhibitors and mucosal protective agent
      can improve gastric ulcer healing.

PMID- 15948256
TI  - CT perfusion at early stage of hepatic diffuse disease.
AB  - AIM: To determine the validity of the non-invasive method of CT perfusion (CTP)
      in rat model of hepatic diffuse disease. METHODS: Twenty-eight Wistar rats were
      divided into two groups. Liver diffuse lesions were induced by diethylnitrosamine
      in 14 rats of test group. Rats in control group were bred with pure water. From
      the 1st to 12th wk after the test group was intervened, both groups were studied
      every week with CTP. CTP parameters of liver parenchyma in different periods and
      pathologic changes in two groups were compared and analyzed. RESULTS: The process
      of hepatic diffuse lesions in test groups was classified into three stages or
      periods according to the pathologic alterations, namely hepatitis, hepatic
      fibrosis, and cirrhosis. During this period, hepatic artery flow (HAF) of control
      group declined slightly, mean transit time (MTT), blood flow (BF) and volume (BV)
      increased, but there were no significant differences between different periods.
      In test group, HAF tended to increase gradually, MTT prolonged obviously, BV and
      BF decreased at the same time. The results of statistical analysis revealed that
      the difference in the HAF ratio of test group to control group was significant.
      The ratio of BV and BF in test group to control group in stage of hepatitis and
      hepatic cirrhosis, hepatic fibrosis and early stage of hepatic cirrhosis was
      significantly different, but there was no significant difference between
      hepatitis and hepatic fibrosis. The main pathological changes in stage of
      hepatitis were swelling of hepatic cells, while sinusoid capillarization and
      deposition of collagen aggravated gradually in the extravascular Disse's spaces
      in stage of fibrosis and early stage of cirrhosis. CONCLUSION: The technique
      could reflect some early changes of hepatic blood perfusion in rat with liver
      diffuse disease and is valuable for their early diagnosis.

PMID- 15948257
TI  - Alpha-catenin expression is decreased in patients with gastric carcinoma.
AB  - AIM: To assess the expression of alpha-catenin in gastric carcinoma and to
      determine the role of alpha-catenin expression in gastric carcinogenesis.
      METHODS: alpha-catenin expression was assessed by semi-quantitative reverse
      transcriptase-polymerase chain reaction and immunohistochemical staining in 49
      gastric carcinomas, 26 adjacent non-cancerous mucosae, and gastric biopsy
      specimens from 11 healthy controls. RESULTS: mRNA levels of alpha-catenin were
      reduced or absent in 34 of 49 (69%) gastric carcinoma tissues and in 5 of 26
      (19%) tumor-free gastric mucosae of carcinoma patients, respectively. Of the
      carcinoma samples with altered alpha-catenin mRNA levels, alpha-catenin
      expression was negative in 20 and decreased in 14 cases. Up to 69% of tumors were
      stained abnormally for alpha-catenin. Of the 34 cases whose mRNA expression of
      alpha-catenin was reduced, 32 (94%) showed abnormal immunostaining patterns,
      while only 2 showed a normal alpha-catenin expression. The frequency of reduced
      expression of alpha-catenin mRNA was 14% in well-differentiated carcinomas,
      higher than that in poorly differentiated carcinomas (86%). A significant
      correlation was not shown between alpha-catenin expression and both depth of
      invasion and lymph node metastasis. Moreover, there was no statistical difference
      between loss or down-regulation of alpha-catenin mRNA and Helicobacter pylori (H.
      pylori) infection. CONCLUSION: Downregulation of alpha-catenin expression is
      common in gastric carcinoma, and alpha-catenin expression may be used as a
      differentiation marker. Downregulation of alpha-catenin expression may be an
      early event in tumorigenesis. Reduced alpha-catenin expression is not correlated
      with H. pylori infection.

PMID- 15948258
TI  - Molecular epidemiological study on pre-X region of hepatitis B virus and
      identification of hepatocyte proteins interacting with whole-X protein by yeast
      two-hybrid.
AB  - AIM: To identify the pre-X region in hepatitis B virus (HBV) genome and to study
      the relationship between the genotype and the pre-X region. To investigate the
      biological function of whole-X (pre-X plus X) protein, we performed yeast two
      hybrid to screen proteins in liver interacting with whole-X protein. METHODS: The
      pre-X region of HBV was amplified by polymerase chain reaction (PCR) method, and
      was cloned to pGEM Teasy vector. After the target region was sequenced, Vector
      8.0 software was used to analyze the sequences. The whole-X bait plasmid was
      constructed by using yeast two-hybrid system 3. Yeast strain AH109 was
      transformed. After expression of the whole-X protein in AH109 yeast strains was
      proved, yeast two-hybrid screening was performed by mating AH109 with Y187
      containing liver cDNA library plasmid. The mated yeast was plated on quadruple
      dropout medium and assayed for alpha-gal activity. The interaction between whole
      X protein and the protein obtained from positive colonies was further confirmed
      by repeating yeast two-hybrid. After extracting and sequencing of plasmid from
      blue colonies, we carried out analysis by bioinformatics. RESULTS: After
      sequencing, 27 of 45 clones (60%) were found encoding the pre-X peptide. Eighteen
      of twenty-seven clones (66.7%) of pre-X coding sequences were found from genotype
      C. Five positive colonies that interacted with whole-X protein were obtained and
      sequenced; namely, fetuin B, UDP glycosyltransferase 1 family-polypeptide A9,
      mannose-P-dolichol utilization defect 1, fibrinogen-B beta polypeptide,
      transmembrane 4 superfamily member 4-CD81 (TM4SF4). CONCLUSION: The pre-X gene
      exists in HBV genome. Genes of proteins interacting with whole-X protein in
      hepatocytes were successfully cloned. These results brought some new clues for
      studying the biological functions of whole-X protein.

PMID- 15948259
TI  - Rat bone marrow mesenchymal stem cells differentiate into hepatocytes in vitro.
AB  - AIM: To investigate the mechanism and regulation of differentiation from bone
      marrow mesenchymal stem cells (MSCs) into hepatocytes and to find a new source of
      cell types for therapies of hepatic diseases. METHODS: MSCs were isolated by
      combining gradient density centrifugation with plastic adherence. The cells were
      cultured in osteogenic or adipogenic differentiation medium and determined by
      histochemical staining. MSCs were plated in plastic culture flasks that were not
      coated with components of extracellular matrix (ECM). When MSCs reached 70%
      confluence, they were cultured in low glucose Dulbecco's modified Eagle's medium
      supplemented with 10 mL/L fetal bovine serum, 20 ng/mL hepatocyte growth factor
      (HGF) and 10 ng/mL fibroblast growth factor-4 (FGF-4). The medium was changed
      every 3 d and stored for albumin, alpha-fetoprotein (AFP) and urea assay.
      Glycogen store of hepatocytes was determined by periodic acid-Schiff staining.
      RESULTS: By combining gradient density centrifugation with plastic adherence, we
      isolated a homogeneous population of cells from rat bone marrow and
      differentiated them into osteocytes and adipocytes. When MSCs were cultured with
      FGF-4 and HGF, approximately 56.6% of cells became small round and epithelioid on
      d 24 by morphology. Compared with the control, levels of AFP increased
      significantly from d 12 to 15.5+/-1.4 microg/L (t = 2.31, P<0.05) in MSCs
      cultured with FGF-4 and HGF, and were higher (46.2+/-1.5 microg/L) on d 21 (t =
      41.926, P<0.01), then decreased to 24.8+/-2.2 microg/L on d 24 (t = 10.345,
      P<0.01). Albumin increased significantly on d 21 (t = 3.325, P<0.01) to 1.4+/-0.2
      microg/mL, and to 2.1+/-0.7 microg/mL on d 24 (t = 3.646, P<0.01). Urea (2.3+/
      0.4 mmol/L) was first detected on d 21 (t = 6.739, P<0.01), and continued to
      increase to 2.6+/-0.9 mmol/L on d 24 (t = 4.753, P<0.01). Glycogen storage was
      first seen on d 21. CONCLUSION: The method combining gradient density
      centrifugation with plastic adherence can isolate MSCs. Rat MSCs may be
      differentiated into hepatocytes by FGF-4 and HGF. Cytokines may play a more
      important role in differentiation from rat MSCs into hepatocytes.

PMID- 15948260
TI  - Comparative proteome analysis of untreated and Helicobacter pylori-treated HepG2.
AB  - AIM: To investigate the pathological effect of Helicobacter pylori (H pylori) on
      human hepatic cells, proteomic methods were used to find and to identify proteins
      that were overexpressed in HepG2 cells treated by H pylori. METHODS: H pylori was
      co-cultured with HepG2 for 6 h. Two-dimensional gel electrophoresis was used to
      gain the protein expression pattern of untreated and H pylori-treated HepG2.
      After staining and image analysis, spots of interest were isolated and subjected
      to mass spectrometry. RESULTS: Seven proteins, which were up-regulated in H
      pylori-treated HepG2 cells, were identified. These proteins included integrin
      beta-1, protein kinase C alpha, LIM/homeobox protein Lhx1, eIF-2-beta, MAP kinase
      kinase 3, PINCH protein and Ras-related protein Rab-37, which involved in
      transcription regulation, signal transduction, metabolism and so on. CONCLUSION:
      H pylori may exert the pathological effect on HepG2 cells by up-regulating the
      expression of some proteins.

PMID- 15948261
TI  - [Sequential liver scintigraphy in the differential diagnosis of focal nodular
      hyperplasia].

PMID- 15948262
TI  - ["Comments on the contribution by B. Kramp und Sylke Graumuller: burning tongue-
      diagnosis and therapy". ].

PMID- 15948263
TI  - [Surgical techniques. Nose, paranasal sinuses, mid-face, orbit, hypophysis. II].

PMID- 15948264
TI  - Characterisation of the Rac/PAK pathway in Amoeba proteus.
AB  - Molecular mechanisms underlying the unique locomotion of the highly motile Amoeba
      proteus still remain poorly understood. Recently, we have shown that blocking the
      endogenous amoebal Rac-like protein(s) leads to distinct and irreversible changes
      in the appearance of these large migrating cells as well as to a significant
      inhibition of their locomotion. To elucidate the mechanism of the Rac pathway in
      Amoeba proteus, we tested the effects of blocking the endogenous myosin I heavy
      chain kinase (MIHCK), one of the Rac effectors in Acanthamoeba castellanii and
      Dictyostelium discoideum, with anti-MIHCK antibodies in migrating amoebae, as
      well as the effect of inhibiting Rac and MIHCK on the actin polymerisation
      process. Antibodies against A. castellanii MIHCK detected an A. proteus protein
      with a molecular mass (ca. 95 kDa) similar to the A. castellanii kinase. The
      cellular distribution of MIHCK in A. proteus was very similar to those of Rac
      like protein in amoebae and MIHCK in A. castellanii. Amoebae microinjected with
      anti-MIHCK antibodies moved slower and protruded fewer wide pseudopodia (5-6)
      than the control cells (9-10), resembling to some extent the phenotype of cells
      microinjected with anti-Rac antibodies. The in vitro studies indicate that the A.
      proteus Rac-like protein, but not the MIHCK isoform, is engaged in the regulation
      of the nucleation step of the actin polymerisation process. These observations
      suggest that MIHCK may be one of the effectors for Rac in these extremely large
      cells.

PMID- 15948265
TI  - Late radiation morbidity following randomization to preoperative versus
      postoperative radiotherapy in extremity soft tissue sarcoma.
AB  - BACKGROUND AND PURPOSE: This study compared late radiation morbidity in patients
      with extremity soft tissue sarcoma randomized to treatment by pre- (50 Gy) or
      postoperative (66 Gy) radiotherapy in combination with surgery. The morbidities
      evaluated included fibrosis, joint stiffness and edema at 2 years following
      treatment. The impact of morbidity on patient function as measured by the
      Musculoskeletal Tumor Rating Scale (MSTS) and the Toronto Extremity Salvage Score
      (TESS) was also evaluated. PATIENTS AND METHODS: 129 patients were evaluated.
      Toxicity rates were compared by treatment arm using the Fisher's exact test.
      Function scores by toxicity were analyzed using the Wilcoxon rank sum test.
      Multivariate logistic regression was used to evaluate the joint effect of
      treatment arm, field size, and dose on subcutaneous tissue fibrosis, joint
      stiffness and edema. RESULTS: 27 of 56 patients (48.2%) in the postoperative arm
      compared to 23 of 73 (31.5%) in the preoperative arm had grade 2 or greater
      fibrosis (P = 0.07). Although not statistically significant, edema was more
      frequent in the postoperative arm, 13 of 56 (23.2%) versus 11 of 73 (15.5%) in
      the preoperative arm, as was joint stiffness, 13 of 56 (23.2%) versus 13 of 73
      (17.8%). Patients with significant fibrosis, joint stiffness or edema had
      significantly lower function scores on both measures (all P-values < 0.01). Field
      size was predictive of greater rates of fibrosis (P = 0.002) and joint stiffness
      (P = 0.006) and marginally predictive of edema (P = 0.06). CONCLUSIONS: Patients
      treated with postoperative radiotherapy tended to have greater fibrosis.
      Fibrosis, joint stiffness and edema adversely affect patient function.

PMID- 15948266
TI  - Mass campaigns and general health services: conclusions. 1965.

PMID- 15948267
TI  - Treatment of localized lymphoma.

PMID- 15948268
TI  - Treatment of localized lymphoma.

PMID- 15948269
TI  - Phase 1 clinical trials in oncology.

PMID- 15948270
TI  - Phase 1 clinical trials in oncology.

PMID- 15948271
TI  - Phase 1 clinical trials in oncology.

PMID- 15948272
TI  - The serotonin syndrome.

PMID- 15948273
TI  - The serotonin syndrome.

PMID- 15948274
TI  - The serotonin syndrome.

PMID- 15948275
TI  - Tenofovir helpful for patients with HBV.

PMID- 15948276
TI  - New PI may offer hope to triple class patients.

PMID- 15948277
TI  - Vaginal gel may prevent herpes transmission.

PMID- 15948278
TI  - Drug being developed to treat cervical dysplasia.

PMID- 15948279
TI  - Summary: take-home points from the Eliminating Adult Immunization Disparities
      Symposium.

PMID- 15948280
TI  - Sharing OR staff can help meet unpredictable staffing demands.

PMID- 15948281
TI  - Report reveals need for better Medicare quality monitoring.

PMID- 15948282
TI  - The conceptual basis of function learning and extrapolation: comparison of rule
      based and associative-based models.
AB  - The purpose of this article is to provide a foundation for a more formal,
      systematic, and integrative approach to function learning that parallels the
      existing progress in category learning. First, we note limitations of existing
      formal theories. Next, we develop several potential formal models of function
      learning, which include expansion of classic rule-based approaches and
      associative-based models. We specify for the first time psychologically based
      learning mechanisms for the rule models. We then present new, rigorous tests of
      these competing models that take into account order of difficulty for learning
      different function forms and extrapolation performance. Critically, detailed
      learning performance was also used to conduct the model evaluations. The results
      favor a hybrid model that combines associative learning of trained input
      prediction pairs with a rule-based output response for extrapolation (EXAM).

PMID- 15948283
TI  - Why is it easier to identify someone close than far away?
AB  - It is a matter of common sense that a person is easier to recognize when close
      than when far away. A possible explanation for why this happens begins with two
      observations. First, the human visual system, like many image-processing devices,
      can be viewed as a spatial filter that passes higher spatial frequencies,
      expressed in terms of cycles/degree, progressively more poorly. Second, as a face
      is moved farther from the observer, the face's image spatial frequency spectrum,
      expressed in terms of cycles/face, scales downward in a manner inversely
      proportional to distance. An implication of these two observations is that as a
      face moves away, progressively lower spatial frequencies, expressed in
      cycles/face--and therefore, progressively coarser facial details--are lost to the
      observer at a rate that is likewise inversely proportional to distance. We
      propose what we call the distance-as-filtering hypothesis, which is that these
      two observations are sufficient to explain the effect of distance on face
      processing. If the distance-as-filtering hypothesis is correct, one should be
      able to simulate the effect of seeing a face at some distance, D, by filtering
      the face so as to mimic its spatial frequency composition, expressed in terms of
      cycles/face, at that distance. In four experiments, we measured face perception
      at varying distances that were simulated either by filtering the face as just
      described or by shrinking the face so that it subtended the visual angle
      corresponding to the desired distance. The distance-as-filtering hypothesis was
      confirmed perfectly in two face perception tasks: assessing the informational
      content of the face and identifying celebrities. Data from the two tasks could be
      accounted for by assuming that they were mediated by different low-pass spatial
      filters within the human visual system that have the same general mathematical
      description but that differ in scale by a factor of approximately 0.75. We
      discuss our results in terms of (1) how they can be used to explain the effect of
      distance on visual processing, (2) what they tell us about face processing, (3)
      how they are related to "flexible spatial scale usage," as discussed by Schyns
      and colleagues, and (4) how they may be used in practical (e.g., legal) settings
      to demonstrate the loss of face information that occurs when a person is seen at
      a particular distance.

PMID- 15948284
TI  - Knowledge of resources and competitors in human foraging.
AB  - The allocation of human participants to resources was studied by observing the
      population dynamics of people interacting in real time within a common virtual
      world. Resources were distributed in two spatially separated pools with varying
      relative reinforcement rates (50-50, 65-35, or 80-20). We manipulated whether the
      participants could see each other and the distribution of the resources. When the
      participants could see each other but not the resources, the richer pool was
      underutilized. When the participants could see the resources but not each other,
      the richer pool was overutilized. In conjunction with prior experiments that
      correlated the visibility of agents and resources (Goldstone & Ashpole, 2004),
      these results indicate that participants' foraging decisions are influenced by
      both forager and resource information. The results suggest that the presence of a
      crowd at a resource is a deterring, rather than an attractive, factor. Both fast
      and slow oscillations in the harvesting rates of the pools across time were
      revealed by Fourier analyses. The slow waves of crowd migration were most
      prevalent when the resources were invisible, whereas the fast cycles were most
      prevalent when the resources were visible and the participants were invisible.

PMID- 15948285
TI  - Prioritization by transients in visual search.
AB  - There is an ongoing debate as to whether prioritizing new objects over old
      objects (the so-called preview benefit) is the result of top-down inhibition of
      old objects (i.e., visual marking; Watson & Humphreys, 1997) or attentional
      allocation to new objects, presented with a luminance transient (Donk & Theeuwes,
      2001). In the two experiments reported here, we tested whether prioritization by
      luminance transients alone can produce a subset-selective search similar to the
      preview effect. Subjects viewed multiobject displays while a subset of objects
      was briefly flashed. The subjects prioritized up to 14 flashed objects over at
      least 14 nonflashed objects. Since prioritization by luminance transients can
      produce a subset-selective search on its own, it may well play an important role
      in the preview benefit.

PMID- 15948286
TI  - Implicit learning of ignored visual context.
AB  - Humans process a visual display more efficiently when they encounter it for a
      second time, showing learning of the display. This study tests whether implicit
      learning of complex visual contexts depends on attention. Subjects searched for a
      white target among black and white distractors. When the locations of the target
      and the attended set (white distractors) were repeated, search speed was
      enhanced, but when the locations of the target and the ignored set (black
      distractors) were repeated, search speed was unaffected. This suggests that the
      expression of learning depends on attention. However, during the transfer test,
      when the previously ignored set now was attended, it immediately facilitated
      performance. In contrast, when the previously attended set now was ignored, it no
      longer enhanced search speed. We conclude that the expression of visual implicit
      learning depends on attention but that latent learning of repeated information
      does not.

PMID- 15948287
TI  - On the categorical nature of the semantic interference effect in the picture-word
      interference paradigm.
AB  - Two picture-word interference experiments are reported in which the boundaries of
      the semantic interference effect are explored. In both experiments, participants
      named pictures (e.g., a picture of a car) that appeared with superimposed word
      distractors. Distractor words from the same semantic category as the word for the
      picture (e.g., CAR) produced semantic interference, whereas semantically related
      distractors from a different category (e.g., BUMPER) led to semantic
      facilitation. In Experiment 2, the semantic facilitation from semantically
      related distractors was replicated. These results indicate that a semantic
      relationship between picture and distractor does not necessarily lead to
      interference and in fact can lead to facilitation. In all but one case tested
      until now, a semantic relationship between picture and distractor has led to
      semantic facilitation. The implications of these results for the assumption that
      the semantic interference effect arises as a consequence of lexical competition
      are discussed.

PMID- 15948288
TI  - The power of a story: new, automatic associations from a single reading of a
      short scenario.
AB  - The implicit association test (IAT) is typically used to assess nonconscious
      categorization judgments that are "under control of automatically activated
      evaluation" (Greenwald, McGhee, & Schwartz, 1998, p. 1464) and that are usually
      considered independent of explicit judgments. The present study builds on recent
      work suggesting evidence of short-term modifiability of the IAT effect.
      Specifically, we show that reading a short text that describes a novel, fictional
      scenario, within which the to-be-evaluated categories are embedded, can produce
      substantial and immediate modulations of the IAT effect. This modulation effect
      does not occur when subjects are simply instructed to think about
      counterstereotypical associations (Experiment 1A and 1B). In Experiment 2, we use
      a variant of the IAT to show that scenario modulation cannot be explained in
      terms of strategic criterion shifts. These results suggest that a newly acquired
      knowledge structure targeting the abstract, category level can produce behavioral
      effects typically associated with automatic categorization.

PMID- 15948289
TI  - Spacing and lag effects in free recall of pure lists.
AB  - Repeating list items leads to better recall when the repetitions are separated by
      several unique items than when they are presented successively; the spacing
      effect refers to improved recall for spaced versus successive repetition (lag > 0
      vs. lag = 0); the lag effect refers to improved recall for long lags versus short
      lags. Previous demonstrations of the lag effect have utilized lists containing a
      mixture of items with varying degrees of spacing. Because differential rehearsal
      of items in mixed lists may exaggerate any effects of spacing, it is important to
      demonstrate these effects in pure lists. As in Toppino and Schneider (1999), we
      found an overall advantage for recall of spaced lists. We further report the
      first demonstration of a lag effect in pure lists, with significantly better
      recall for lists with widely spaced repetitions than for those with moderately
      spaced repetitions.

PMID- 15948291
TI  - Analysis of chromosome/allele loss in genetically unstable yeast by quantitative
      real-time PCR.

PMID- 15948290
TI  - Novel approaches to the management of myeloma.
AB  - Standard therapy for multiple myeloma, which accounts for 10% of all hematologic
      malignancies, has been autologous stem cell transplantation (ASCT), alkylator
      based chemotherapy, and corticosteroids. Several advances have been made in the
      treatment of multiple myeloma over the past decade, especially the arrival of
      new, active agents such as thalidomide (Thalomid), bortezomib (Velcade), and
      lenalidomide (Revlimid). These have shown significant clinical activity as single
      agents. Trials are ongoing to incorporate these new agents into the various
      stages of treatment and to combine them with other effective treatment
      modalities, including ASCT.

PMID- 15948292
TI  - Housekeeping genes in cancer: normalization of array data.
AB  - Biological maintenance of cells under variable conditions should affect gene
      expression of only certain genes while leaving the rest unchanged. The latter,
      termed "housekeeping genes," by definition must reflect no change in their
      expression levels during cell development, treatment, or disease state anomalies.
      However, deviations from this rule have been observed. Using DNA microarray
      technology, we report here variations in expression levels of certain
      housekeeping genes in prostate cancer and a colorectal cancer gene therapy model
      system. To highlight, differential expression was observed for ribosomal protein
      genes in the prostate cancer cells and beta-actin in treated colorectal cells.
      High-throughput differential gene expression analysis via microarray technology
      and quantitative PCR has become a common platform for classifying variations in
      similar types of cancers, response to chemotherapy, identifying disease markers,
      etc. Therefore, normalization of the system based on housekeeping genes, such as
      those reported here in cancer, must be approached with caution.

PMID- 15948293
TI  - Enzymatic mutation detection technologies.
AB  - Mutation is as necessary for life as fidelity is in DNA replication. The study of
      mutations reveals the normal functions of genes, messages, proteins, the causes
      of many diseases, and the variability of responses among individuals. Indeed,
      recent mutations that have not yet become polymorphisms are often deleterious and
      pertinent to the disease history of afflicted individuals. This review discusses
      the principles behind a variety of methods for the detection of mutations and
      factors that should be considered in future methods design. One enzymatic
      approach in particular using orthologs of the CEL I nuclease that show high
      specificity for all mismatches, appears to be easy and robust. Further
      developments of this and other methods will allow mutation detection to become an
      integral component of individualized medicine.

PMID- 15948294
TI  - Features of porcine circovirus-2 disease: correlations between lesions, amount
      and distribution of virus, and clinical outcome.
AB  - Tissue sets from 36 snatch-farrowed colostrum-deprived (SF/CD) and 71 Caesarian
      derived gnotobiotic swine infected with porcine circovirus type 2 (PCV-2) as
      neonates were examined and scored for the types and tissue distribution of
      histologic lesions associated with this viral infection. The occurrence and
      severity of these lesions were correlated with qualitative and quantitative
      determinations of viral burden in tissues by immunohistochemistry (IHC) and
      tissue titrations for infectious virus, respectively. These measures were, in
      turn, related to 1 of 3 categories of clinical disease expressed in PCV-2
      infected swine as subclinical infection, preclinical postweaning multisystemic
      wasting syndrome (PMWS), and clinically evident PMWS, respectively. Statistically
      significant (P < 0.05 to 0.001) associations between both measures of viral
      burden, the severity of histologic lesions and the stage of disease were
      obtained. Discrimination between and among categories of disease was best
      accomplished by a combination of IHC and histopathology. The results of this
      study confirm that viral burden in PCV-2-infected tissues, specifically lymphoid
      tissues and liver, directly correlate with severity of clinical disease
      expression in PCV-2 infected swine.

PMID- 15948295
TI  - Multimodal assessment after surgery for cervical spondylotic myelopathy.
AB  - OBJECT: Investigators reporting decompressive surgery to treat patients with
      cervical spondylotic myelopathy (CSM) have described inconsistent benefits. In
      the present study the authors used three types of outcomes instruments to assess
      the results of CSM surgery. METHODS: The authors collected prospective baseline
      and 6-month follow-up data in a cohort of 62 patients with CSM. Data collection
      included those pertaining to demographics; symptoms; physical findings;
      myelopathy severity; health status measured with the Short Form-36; and health
      values according to the standard gamble, time trade-off, visual analog scale, and
      willingness to pay. Rank-order methods were used to compare surgical and
      nonsurgical patients, and multivariate regression techniques adjusting for
      baseline characteristics were performed to examine the effects of surgery. During
      the study period, 28 patients underwent surgery, 34 did not, and there were no
      baseline differences between the two groups in demographics, symptoms, myelopathy
      scores, health status, or health values (p > or = 0.120 in all domains); there
      was a greater prevalence of hand intrinsic muscle atrophy (p = 0.035) and
      Hoffmann sign (p = 0.006) in the surgery-treated group. Neither raw comparisons
      nor regression analyses showed a consistent surgery-related benefit. There were
      sporadic associations between worse outcomes and older patients, higher income,
      Babinski sign, longer duration of CSM symptoms, hand clumsiness, lower-extremity
      numbness, and multilevel surgery (p < or = 0.049 for all). CONCLUSIONS: Analysis
      of results obtained in the 62 patients with CSM failed to show a surgery-related
      benefit despite the use of three classes of outcomes instruments. Patient
      demographics, symptoms, physical signs, and the surgical approach may explain
      some of the variation in outcomes in patients with CSM.

PMID- 15948296
TI  - Review: tubulin function, action of antitubulin drugs, and new drug development.
AB  - Anticancer agents that interfere with microtubulin function are in widespread use
      in man and have a broad spectrum of activity against both hematological
      malignancies and solid tumors. The mechanisms of actions of these agents have
      been better defined during the past decade, indicating that there are distinct
      binding sites for these agents and that they interfere with microtubulin dynamics
      (growth and shortening of tubules) at low concentrations and only evoke
      microtubulin aggregation or dissociation at high concentrations. Tubulin has been
      recently described in the nucleus of cells and in mitochondria. Downstream events
      from tubulin binding are believed to be critical events for the generation of
      apoptosis in the malignant cell. The effects of vinca alkaloids and taxanes are
      distinct, suggesting that the interference with the tubulin cap by high-affinity
      binding of effective agents is not the only mechanism of cytotoxic effect, and
      the low-affinity binding of drug, which distorts microtubulin function, may also
      be important. The epothilones share some of the binding characteristics of the
      taxanes and are in clinical trials because of cytoxic activity in taxane
      resistant cells. Tubulin has additional target sites for anticancer drugs
      including interference with the binding and function of microtubule associated
      proteins and interference with motor proteins which are essential for the
      transport of substances within the cell. Because many of these microtubule
      associated proteins have an ATP binding site, both computer-aided design and
      combinatorial chemistry techniques can be used to make agents to interfere with
      their function analogous to imatinib mesylate (Gleevec). Agents that interfere
      with the motor protein kinesin are entering clinical trials.

PMID- 15948297
TI  - Elevated fibroblast growth factor 23 in women with malignant ovarian tumors.
AB  - OBJECTIVE: To determine whether fibroblast growth factor 23 (FGF23)
      concentrations are altered in women with ovarian cancers in which FGF physiology
      is known to be abnormal. PATIENTS AND METHODS: Between May 2002 and September
      2003 at the Mayo Clinic in Rochester, Minn, plasma or serum FGF23 concentrations
      were measured in 39 healthy women and in 14 with benign ovarian tumors, 14 with
      early-stage ovarian cancer, and 13 with advanced-stage ovarian cancer.
      Immunohistochemistry using anti-human FGF23 antibodies was performed on tissue
      from benign masses and advanced-stage tumors. RESULTS: Serum or plasma FGF23
      concentrations were significantly higher in women with advanced-stage ovarian
      cancer compared with concentrations in women with early-stage ovarian cancer or
      benign disease or in healthy women. A significant positive correlation was seen
      between serum iFGF23 and cFGF23 concentrations and stage of disease. Serum iFGF23
      and cFGF23 concentrations were positively correlated with serum phosphorus among
      women with ovarian cancer. No patients with elevated iFGF23 or cFGF23
      concentrations had hypophosphatemia. Immunohistochemistry detected FGF23 tissue
      staining in malignant ovarian cancer cells. CONCLUSION: Serum or plasma FGF23
      concentrations are elevated in patients with advanced-stage epithellal ovarian
      cancer without reductions in serum phosphate concentrations. The presence of
      elevated FGF23 concentrations in patients with an ovarian mass should suggest
      advanced-stage disease.

PMID- 15948298
TI  - Long-term trends in thyroid carcinoma: a population-based study in Olmsted
      County, Minnesota, 1935-1999.
AB  - OBJECTIVE: To determine whether there was a significant increase in the incidence
      of thyroid carcinoma in Olmsted County, Minnesota, that may be attributed to the
      widespread use of therapeutic head and neck irradiation between 1920 and the
      1950s or to exposure to atomic fallout at the Nevada Test Site in the 1960s.
      METHODS: Rochester Epidemiology Project resources were used to identify potential
      cases of thyroid carcinoma among residents of Olmsted County between 1935 and
      1984. We extended this earlier study through 1999. RESULTS: During the study
      period, thyroid carcinoma was newly diagnosed in 263 residents. In women, the age
      adjusted incidence increased from 2.7 per 100,000 person-years (p-y) in 1935-1949
      to 9.2 per 100,000 p-y in 1990-1999 (P = .001); In men, the rate increased from
      0.8 to 5.0 per 100,000 p-y (P = .007). However, most of the increase occurred
      before 1965 and remained relatively stable thereafter. Similar trends were
      observed for papillary carcinoma alone. CONCLUSION: Although the Incidence of
      thyroid carcinoma increased significantly between 1935 and 1964, no significant
      Increases have been seen since 1965, suggesting that neither atmospheric atomic
      fallout from the Nevada Test Site nor use of ionizing radiation to treat
      conditions of the head and neck significantly affected the incidence of thyroid
      carcinoma in Olmsted County.

PMID- 15948299
TI  - Limitations of using outcomes in the placebo arm of a clinical trial of benign
      prostatic hyperplasia to quantify those in the community.
AB  - OBJECTIVES: To quantify potential biases that may occur when placebo arms of
      clinical trials are used to characterize the natural history of disease and to
      compare incidence rates of benign prostatic hyperplasia (BPH) outcomes in
      community-dwelling men with outcomes in the placebo arm of a clinical trial of
      BPH. SUBJECTS AND METHODS: White men aged 50 years or older at baseline were
      selected randomly from the Olmsted County, Minnesota, community in 1990 and were
      monitored biennially through 1996 for urologic outcomes. Symptom progression,
      acute urinary retention, and minimally Invasive or surgical treatment of BPH were
      assessed from a validated questionnaire and a review of community medical
      records. Findings from the Olmsted County Study (N=1193) and a selected subcohort
      (n=238) were compared with those from the placebo arm of the Medical Therapy of
      Prostatic Symptoms trial (N=737). RESULTS: During more than 5088 person-years of
      follow-up (mean, 4.9 years) In the Olmsted County Study, Incidence rates per 1000
      person-years were 8.5 (95% confidence Interval [CI], 6.4-11.2) for acute urinary
      retention, 97.1 (95% CI, 88.7-106.0) for symptom progression, 6.6 (95% CI, 4.8
      9.0) for surgery or minimally invasive treatment, and 105.1 (95% CI, 96.4-114.4)
      for any outcomes for all men. For those meeting trial Inclusion criteria
      (selected subcohort, n=238), Incidence rates were 18.3, 86.5, 16.8, and 109.4,
      respectively. By comparison, Incidence rates per 1000 person-years for the
      placebo arm of the Medical Therapy of Prostatic Symptoms clinical trial for BPH
      (mean follow-up, 4.5 years) were 6 for acute urinary retention, 36 for symptom
      progression, and 45 for any outcome, but the estimate of 13 for surgery or
      minimally invasive treatment was higher than for men in the Olmsted County Study.
      CONCLUSIONS: Compared with community-dwelling men, men in the placebo arm of this
      clinical trial of BPH treatments had a substantially lower risk of BPH-related
      outcomes. Extrapolation of findings from the placebo arm of clinical trials to
      describe the natural history of disease in community-dwelling men should be done
      with caution and appropriate recognition of limitations.

PMID- 15948300
TI  - Calcification of the coronary arteries in the absence of atherosclerotic plaque.
AB  - Arterial calcification in the coronary arteries frequently indicates concomitant
      atherosclerotic plaque but can be present in the medial layers with no evidence
      of plaque. Calcification of the medial layer of arteries is seen most often in
      the peripheral arteries but also is widely recognized In the coronary arteries.
      We describe 2 patients who had marked medial and intimal calcification of the
      coronary arteries with little or no accompanying atherosclerosis.

PMID- 15948301
TI  - Impact of depressive symptoms on adult asthma outcomes.
AB  - BACKGROUND: Psychological disorders, including depression, are common in adults
      with asthma. Although depression is treatable, its impact on longitudinal asthma
      outcomes is not clear. OBJECTIVE: To elucidate the impact of depressive symptoms
      on patient-centered outcomes and emergency health care use in adults with asthma.
      METHODS: We conducted a prospective cohort study of 743 adults with asthma who
      were recruited after hospitalization for asthma. Depressive symptoms were defined
      as having a score of 16 or more on the Center for Epidemiologic Studies
      Depression Scale. We examined the impact of depressive symptoms on patient
      centered outcomes (validated severity-of-asthma score, Marks Asthma Quality of
      Life Questionnaire, and 12-Item Short-Form Health Survey physical component
      summary score) and on future emergency health care use for asthma ascertained
      from computerized databases. RESULTS: The prevalence of depressive symptoms was
      18% (95% confidence interval [CI], 15%-21%) among adults with asthma. Depressive
      symptoms were associated with greater severity-of-asthma scores after controlling
      for age, sex, race/ ethnicity, educational attainment, and cigarette smoking
      (mean score increment, 2.6 points; 95% CI, 1.8-3.4 points). Furthermore,
      depressive symptoms were associated with poorer asthma-specific quality of life
      (mean score increment, 19.9 points; 95% CI, 17.7-22.1 points) and poorer physical
      health status (mean score decrement, 3.7 points; 95% CI, 1.5-5.8 points).
      Depressive symptoms were associated with a greater longitudinal risk of
      hospitalization for asthma (hazard ratio, 1.34; 95% CI, 0.98-1.84). After
      controlling for differences in preventive care for asthma, the relationship was
      stronger (hazard ratio, 1.45; 95% CI, 1.05-2.0). CONCLUSION: Depressive symptoms
      are common in adults with asthma and are associated with poorer health outcomes,
      including greater asthma severity and risk of hospitalization for asthma.

PMID- 15948303
TI  - Biological and social predictors of long-term geriatric depression outcome.
AB  - OBJECTIVE: In this study, we examined 204 older depressed individuals for up to
      64 months to determine factors related to depression outcome. We hypothesized
      that both presence of vascular brain lesions seen on baseline magnetic resonance
      imaging (MRI) scans and lower baseline social support measures would be related
      to worse depression outcome. METHOD: At study entry, all subjects were at least
      59 years old, had a diagnosis of major depression, and were free of other major
      psychiatric illness and primary neurological illness, including dementia and
      stroke. Depression was diagnosed via structured interview and clinical assessment
      by a geriatric psychiatrist who completed a Montgomery Asberg Depression Rating
      Scale (MADRS) to determine severity of depression. Subjects provided self-report
      data on social support variables and ability to perform basic and instrumental
      activities of daily living (ADL, IADL). All subjects agreed to have a baseline
      standardized MRI brain scan. Ratings of severity of hyperintensities were
      determined for the periventricular white matter, deep white matter, and
      subcortical gray matter by two readers who decided by consensus. Treatment was
      provided by geropsychiatrists following clinical guidelines. Using mixed models
      to analyze the data, we determined the effect of a variety of demographic, social
      and imaging variables on the trajectory of MADRS score, the outcome variable of
      interest. RESULTS: MADRS scores decreased steadily over time. In a final HLM
      model, in which time since entry, a baseline time indicator, age, gender,
      education and Mini-mental State Examination score were controlled, subjective
      social support, instrumental ADL impairment, subcortical gray matter severity,
      and the interactions of time with social network and with subcortical gray matter
      lesions remained significantly associated with MADRS score. CONCLUSIONS: Both
      social and biological factors at baseline are associated with longitudinal
      depression severity in geriatric depression.

PMID- 15948306
TI  - Electronic products; performance standard for diagnostic x-ray systems and their
      major components. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule to amend the
      Federal performance standard for diagnostic x-ray systems and their major
      components (the performance standard). The agency is taking this action to update
      the performance standard to account for changes in technology and use of
      radiographic and fluoroscopic x-ray systems and to fully utilize the
      International System of Units to describe radiation-related quantities and their
      units when used in the performance standard. For clarity and ease of
      understanding, FDA is republishing the complete contents, as amended, of three
      sections of the performance standard regulations and is amending a fourth section
      without republishing it in its entirety. This action is being taken under the
      Federal Food, Drug, and Cosmetic Act (the act), as amended by the Safe Medical
      Devices Act of 1990 (SMDA).

PMID- 15948302
TI  - Mouse exposure and wheeze in the first year of life.
AB  - BACKGROUND: Studies have found that exposure to mice is highly prevalent among
      children with asthma living in urban areas. OBJECTIVE: To examine the
      relationship between exposure to mice and wheeze in the first year of life.
      METHODS: We conducted an ongoing prospective birth cohort study of 498 children
      with a history of allergy or asthma in at least 1 parent living in metropolitan
      Boston (the Home Allergens and Asthma Study). RESULTS: In a multivariate
      analysis, infants whose parents reported exposure to mice in the household had
      nearly twice the odds of developing any wheeze in the first year of life as
      children without exposure (odds ratio [OR], 1.83; 95% confidence interval [CI],
      1.14-2.95; P = .01). Other variables associated with wheeze in the first year of
      life included low birth weight (OR, 1.77; 95% CI, 1.06-2.95; P = .03), having at
      least 1 lower respiratory tract illness (OR, 5.59; 95% CI, 3.46-9.04; P < .001),
      exposure to high levels of endotoxin at age 2 to 3 months (fourth quartile
      compared with first quartile: OR, 2.32; 95% CI, 1.19-4.54; P = .01), and exposure
      to cockroach allergen of 0.05 U/g of dust or more at age 2 to 3 months (OR, 1.83;
      95% CI, 1.09-3.08; P = .02). CONCLUSION: Among children with a parental history
      of asthma or allergies, exposure to mice is associated with wheeze in the first
      year of life, independent of other factors.

PMID- 15948307
TI  - Current awareness in prenatal diagnosis.

PMID- 15948308
TI  - Leprosy elimination not yet in sight.

PMID- 15948309
TI  - Widows, women, and the bioethics of care.
AB  - Widows, women, and the bioethics of care must be understood within an authentic
      Christian ontology of gender. Men are men and women are women, and their being is
      ontologically marked in difference. There is an ontology of gender with important
      implications for the role of women in the family and the Church. The Christian
      Church has traditionally recognized a role for widows, deaconesses, and female
      monastics, which is not that of the liturgical priesthood, but one with a special
      relationship to care and therefore with particular implications for health care
      and a Christian bioethics of care in the twenty-first century. In the shadow of
      early male mortality, women as wives should turn to support their husbands and as
      widows to support those in need. Widows, in becoming authentic Christian
      monastics, can bring into the world an icon of rightly ordered women providing
      rightly ordered Christian care for those in need. They can enter the moral vacuum
      created by misunderstandings of the place of women and the service vacuum created
      by a disappearance of religious nuns in Western health care facilities with a
      presence that is at one with the Church of the Fathers.

PMID- 15948310
TI  - Marburg fever in Angola: still a mystery disease.

PMID- 15948311
TI  - Influenza A H2N2 saga remains unexplained.

PMID- 15948312
TI  - Roll Back Malaria issue first global report.

PMID- 15948313
TI  - Ethics of AIDS drug trials on foster children questioned.

PMID- 15948314
TI  - Human cost of AIDS drugs scam.

PMID- 15948315
TI  - US paediatric vaccine stockpile falling short.

PMID- 15948316
TI  - Harvard accused of delaying HIV treatment programme.

PMID- 15948319
TI  - Consolidating genetic data.

PMID- 15948318
TI  - Modification by the tissue plasminogen activator-plasmin system of morphine
      induced dopamine release and hyperlocomotion, but not anti-nociceptive effect in
      mice.
AB  - The extracellular serine protease tissue plasminogen activator (tPA) that
      converts plasminogen into plasmin is abundantly expressed throughout the central
      nervous system. We have recently demonstrated that the tPA-plasmin system
      participates in the rewarding and locomotor-stimulating effects of morphine by
      acutely regulating morphine-induced dopamine release in the nucleus accumbens
      (NAc). In the present study, we examined the effects of microinjections of
      plasminogen activator inhibitor-1 (PAI-1), tPA or plasmin into the NAc on
      morphine-induced dopamine release, hyperlocomotion and anti-nociceptive effects
      in ICR mice. A single morphine treatment resulted in an increase in protein
      levels of PAI-1 in the NAc. Microinjection of PAI-1 into the NAc dose-dependently
      reduced morphine-induced dopamine release and hyperlocomotion. In contrast,
      microinjection of tPA into the NAc significantly potentiated morphine-induced
      dopamine release and hyperlocomotion without affecting basal levels. Furthermore,
      microinjection of plasmin enhanced morphine-induced dopamine release, but did not
      modify the hyperlocomotion induced by morphine. The intracerebroventricular
      injection of PAI-1, tPA and plasmin at high doses had no effect on the anti
      nociceptive effects of morphine. These results suggest that the tPA-plasmin
      system is involved in the regulation of morphine-induced dopamine release and
      dopamine-dependent behaviors but not the anti-nociceptive effects of morphine.

PMID- 15948320
TI  - Combination chemotherapy for advanced pancreatic cancer--has its time finally
      come?

PMID- 15948321
TI  - UK clinicians to screen embryos for BRCA mutations.

PMID- 15948322
TI  - Safer central venous access.

PMID- 15948323
TI  - Safer central venous access.

PMID- 15948324
TI  - Research on stored biological samples: the views of Ugandans.

PMID- 15948326
TI  - Determining the level of statistician participation on Canadian-based research
      ethics boards.

PMID- 15948325
TI  - Just-in-time IRB review: capitalizing on scientific merit review to improve human
      subjects research compliance.

PMID- 15948327
TI  - Contraception in research: a policy suggestion.

PMID- 15948328
TI  - Health, happiness and health promotion.
AB  - This article claims that health promotion is best practiced in the light of an
      Aristotelian conception of the good life for humans and of the place of health
      within it.

PMID- 15948329
TI  - Animals, pain and morality.
AB  - While it is widely agreed that the infliction upon innocents of needless pain is
      immoral, many have argued that, even though nonhuman animals act as if they feel
      pain, there is no reason to think that they actually suffer painful experiences.
      And if our actions only appear to cause nonhuman animals pain, then such actions
      are not immoral. On the basis of the claim that certain behavioural responses to
      organismic harm are maladaptive, whereas the ability to feel pain is itself
      adaptive, this article argues that the experience of pain should be viewed as the
      proximate cause of such occasionally maladaptive behaviour. But as nonhuman
      animals also display such maladaptive traits, we have reason to conclude that
      they feel pain. Hence, we have reason to hold that it is indeed possible to
      inflict needless pain on nonhuman animals, which would be immoral.

PMID- 15948331
TI  - Clinics' bid to withhold abortion files is criticized.

PMID- 15948330
TI  - Amputees by choice: body integrity identity disorder and the ethics of
      amputation.
AB  - Should surgeons be permitted to amputate healthy limbs if patients request such
      operations? We argue that if such patients are experiencing significant distress
      as a consequence of the rare psychological disorder named Body Integrity Identity
      Disorder (BIID), such operations might be permissible. We examine rival accounts
      of the origins of the desire for healthy limb amputations and argue that none are
      as plausible as the BIID hypothesis. We then turn to the moral arguments against
      such operations, and argue that on the evidence available, none is compelling.
      BIID sufferers meet reasonable standards for rationality and autonomy: so as long
      as no other effective treatment for their disorder is available, surgeons ought
      to be allowed to accede to their requests.

PMID- 15948332
TI  - Drug makers are still giving gifts to doctors, F.D.A. officials tell senators.

PMID- 15948333
TI  - Kant, Mill, Durkheim? Trust and autonomy in bioethics and politics.

PMID- 15948334
TI  - Biological explanations and social responsibility.
AB  - The aim of this paper is to show that critics of biological explanations of human
      nature may be granting too much to those who oppose such explanations when they
      argue that the truth of genetic determinism implies an end to critical evaluation
      and reform of our social institutions. This is the case because when we argue
      that biological determinism exempts us from social critique we are erroneously
      presupposing that our social values, practices, and institutions have nothing to
      do with what makes biological explanations troublesome. My argument is that what
      constitutes a problem for those who are concerned with social justice is not the
      fact that particular behaviours may be genetically determined, but the fact that
      our value system, and social institutions create the conditions that make such
      behaviours problematic. Thus, I will argue that even if genetic determinism were
      correct, the requirement of assessing and transforming our social practices and
      institutions would be far from superfluous. Biology is rarely destiny for human
      beings and the institutions they create.

PMID- 15948335
TI  - Health care ethics and health law in the Dutch discussion on end-of-life
      decisions: a historical analysis of the dynamics and development of both
      disciplines.
AB  - Over the past three or four decades, the concept of medical ethics has changed
      from a limited set of standards to a broad field of debate and research. We
      define medical ethics as an arena of moral issues in medicine, rather than a
      specific discipline. This paper examines how the disciplines of health care
      ethics and health care law have developed and operated within this arena. Our
      framework highlights the aspects of jurisdiction (Abbott) and the assignment of
      responsibilities (Gusfield). This theoretical framework prompted us to study
      definitions and changing responsibilities in order to describe the development
      and interaction of health care ethics and health law. We have opted for the
      context of the Dutch debate about end-of-life decisions as a relevant case study.
      We argue that the specific Dutch definition of euthanasia as 'intentionally
      taking the life of another person by a physician, upon that person's request' can
      be seen as the result of the complex jurisdictional process. This illustrates the
      more general conclusion that the Dutch debate on end-of-life decisions and the
      development of the two disciplines must be understood in terms of mutual
      interaction.

PMID- 15948336
TI  - Why I was never a zygote.

PMID- 15948337
TI  - What are persons made of?
AB  - Many current debates between Catholic and secular bioethicists stalemate upon one
      central dispute: whether human dignity is a property persons bear at conception,
      or a product of social engagement, i.e., whether persons are born, or made. We
      need not resolve that dispute, however, to affirm two points that the prospect of
      human cloning should teach us. First, whether persons are born or made, whether
      we affirm a creationist, traducian, or even reincarnational view of the soul, the
      prospect of cloning highlights the inescapably communitarian dimensions of human
      dignity. Second, within a pluralist moral culture, we're best advised to conceive
      human dignity not only as a property ascribed to us through divine grace, but
      also as an ethical imperative to be inscribed, by us, in the dignifying social
      practices by which we bear and raise persons.

PMID- 15948338
TI  - Racism and human genome diversity research: the ethical limits of "population
      thinking".
AB  - This paper questions the prevailing historical understanding that scientific
      racism "retreated" in the 1950s when anthropology adopted the concepts and
      methods of population genetics and race was recognized to be a social construct
      and replaced by the concept of population. More accurately, a "populational"
      concept of race was substituted for a "typological one"--this is demonstrated by
      looking at the work of Theodosius Dobzhansky circa 1950. The potential for
      contemporary research in human population genetics to contribute to racism needs
      to be considered with respect to the ability of the typological-population
      distinction to arbitrate boundaries between racist society and nonracist, even
      anti-racist, science. I point out some ethical limits of "population thinking" in
      doing so.

PMID- 15948339
TI  - Surgical research and the ethics of being first.

PMID- 15948340
TI  - Koreans report ease in cloning for stem cells; work on human embryos; researchers
      say goal is better medicine, not reproduction.

PMID- 15948341
TI  - Court to tackle abortion again after 5 years; parent notification case; in
      considering technical issues, justices rejoin a fractious debate.

PMID- 15948342
TI  - In political step, Pope joins fray on fertility law.

PMID- 15948343
TI  - Child abuse.

PMID- 15948344
TI  - A 14-year-old girl with ADHD and hepatitis.

PMID- 15948345
TI  - A 25-month-old girl with progressive pruritic eruptions.

PMID- 15948346
TI  - Barriers to physician identification and reporting of child abuse.
AB  - Physicians systematically underidentify and underreport cases of child abuse.
      These medical errors may result in continued abuse, leading to potentially severe
      consequences. We have reviewed a number of studies that attempt to explain the
      reasons for these errors. The findings of these various studies suggest several
      priorities for improving the identification and reporting of child maltreatment:
      Improve continuing education about child maltreatment. Continuing education
      should focus not only on the identification of maltreatment but also on
      management and outcomes. This education should include an explanation of the role
      of CPS investigator and the physician's role in an investigation. The education
      should provide physicians with a better understanding of the overall outcome for
      children reported to CPS to help physicians gain perspective on the small number
      of maltreated children they may care for in their practice. This education should
      emphasize that the majority of maltreated children will benefit from CPS
      involvement. New York is the only state that mandates all physicians, as well as
      certain other professionals, take a 2-hour course called Identification and
      Reporting of Child Abuse and Maltreatment prior to licensing. Cited studies in
      this article suggest that such a mandate might be expected to improve
      identification and reporting, thereby encouraging other states to adopt similar
      regulations. Give physicians the opportunity to debrief with a trained
      professional after detecting and reporting child abuse. The concept of child
      abuse and the gravity of the decision to report can be troubling to the reporter.
      The debriefing could include discussions of uncomfortable feelings physicians may
      experience related to their own countertransference reactions. Provide resources
      to assist physicians in making the difficult determination of suspected
      maltreatment. The role of accessible telephone consultation should be evaluated,
      along with formalized collaborations with local Emergency Departments with
      pediatric expertise. Improve the relationship between CPS and medical providers.
      For example, CPS workers should systematically inform the reporting physician
      about the progress of their investigation and the outcome for the child and
      family. Several past reports have made specific suggestions to improve the
      working relationship. Warner and Hanson recommended that positive outcomes be
      programmed into the reporting process. They suggested that CPS have special phone
      lines staffed by well-trained employees for mandated reporters to call. Finkelhor
      and Zellman proposed a more radical change to improve the working relationship
      between CPS and mandated reporters. They suggested that certain professionals,
      with demonstrated expertise in the recognition and treatment of child abuse and
      registered as such, should have "flexible reporting options." Options include the
      ability to defer reporting, if there are no immediate threats to a child, or to
      make a report in confidence and defer the investigation until necessary.
      Finkelhor and Zellman emphasized that this model would improve physician
      reporting compliance and enhance the role of CPS while reducing the work burden
      for CPS. Improve interaction with the legal system. Child abuse pediatric experts
      who have courtroom experience could provide education and support to physicians
      who have little preexisting experience with the legal system. Reimbursement for
      time spent supporting legal proceedings should be equitable and may reduce
      physician concerns about lost patient revenue. Retrospective studies and vignette
      analyses provide much information about some of the barriers to child
      maltreatment reporting and describe many of the reasons why physicians do not
      identify and report all child maltreatment. Future prospective examinations of
      physician decision-making may further explain the physician's decision-making
      process and the barriers he or she faces when identifying and reporting child
      abuse.

PMID- 15948347
TI  - Diagnosing pediatric head trauma.
AB  - The accurate diagnosis and successful management of pediatric abusive head trauma
      present pediatricians with many unique challenges. To overcome these challenges
      requires a high index of clinical suspicion; a willingness to report any
      suspicion of abuse; knowledge of the relevant medical literature; a direct,
      nonaccusatory, and supportive approach with parents; thorough history taking;
      meticulous physical examination; and most important, professional objectivity and
      integrity. Your patients deserve no less.

PMID- 15948348
TI  - Accidental or inflicted?
AB  - The visible evidence of child physical abuse most often is minimal or
      nonexistent, and the children at greatest risk of becoming victims are those too
      young to verbalize the history. As pediatric clinicians, we must be able to
      recognize potential sequelae of abuse and the high-risk situations that lead to
      physical abuse; we also must acknowledge that victims of child physical abuse
      often have injuries at multiple locations and in multiple organ systems. As a
      routine part of pediatric practice, healthcare providers, through anticipatory
      guidance, try to maximize the child's safety in the home environment. With this
      goal in mind, healthcare providers must consider the possibility of physical
      abuse when faced with a child with a traumatic injury. While it is important to
      identify these inflicted injuries, our ultimate goal is to prevent their
      occurrence in the first place.

PMID- 15948349
TI  - Evaluating child sexual abuse.
AB  - We have learned much about the medical evaluation of suspected child sexual abuse
      during the past 2 decades. The physical examination still holds an important
      place in the evaluation but is secondary to a well-performed history. As the
      evolving literature increases our understanding, the relevance of various
      anatomic appearances of the prepubertal and pubertal genital examination will
      certainly become even clearer. The physical examination rarely is diagnostic by
      itself, with more than 92% of cases failing to demonstrate either acute or
      chronic signs of injury. Thus, the 1994 quote by Adams and colleagues, "It's
      normal to be normal," continues to ring true, now supported by a growing body of
      pediatric literature.

PMID- 15948350
TI  - Recognizing and responding to domestic violence.

PMID- 15948351
TI  - Internet poses multiple risks to children and adolescents.
AB  - Computers and Internet usage, whether by children at home or at public places
      such as schools and libraries, are here to stay. Tremendous benefits in terms of
      educational opportunities, communication, and recreation can be expected. With
      all the benefits that such information technology provides, however, there is an
      element of risk that should not inhibit its use but must be attended to and
      managed. The methods child sexual offenders use to pursue their criminal
      interests will continue to evolve as technology evolves. The first and most
      important line of defense calls for parents and other caregivers to remain
      directly responsible for the safety of the children in their care. Parents,
      teachers, healthcare providers, and other caregivers need to learn continually
      about the Internet and remain aware of how best to protect children who use the
      computer and the Internet. Law enforcement agencies must also continue to prepare
      for advances in computer technology, to better anticipate the behavior of child
      sexual offenders, and to investigate and prosecute offenders. All law
      enforcement, medical, and social services personnel who have contact with
      children on a regular basis must continue to educate children and their parents
      or guardians about the dangers posed by the Internet. After a child is
      victimized, law enforcement, medical, and social services personnel also must
      remain cognizant that the victim's computer may contain evidence that may help
      identify and prosecute the offender. In short, all those charged with the
      protection of children and the prosecution of child sexual offenders must
      continue to adapt to our ever-evolving computer technology.

PMID- 15948352
TI  - Understanding child abusers.

PMID- 15948353
TI  - Terrorists posing as JCAHO surveyors? Act now to make your security airtight.

PMID- 15948354
TI  - Have you implemented a rapid response team?

PMID- 15948355
TI  - Patient satisfaction planner. Reduce chaos to see satisfaction scores rise.

PMID- 15948356
TI  - Patient satisfaction planner. Technology, planning key to successful programs.

PMID- 15948357
TI  - Learn to use a 'what-if' patient safety analysis.

PMID- 15948358
TI  - Protocol reduces mortality rates for hip fracture 80%.

PMID- 15948359
TI  - Expedited treatment for partners of patients with gonorrhea and/or chlamydial
      infection: impact on rates of persistence or recurrence.

PMID- 15948360
TI  - Irritable bowel syndrome: the possible benefits of probiotics.

PMID- 15948361
TI  - Cytomegalovirus DNA: a common finding in the hearts of patients with fatal
      myocarditis.

PMID- 15948362
TI  - Calprotectin: a predictive marker of a relapse in ulcerative colitis.

PMID- 15948363
TI  - Curbing the psoriasis cascade. Therapies to minimize flares and frustration.
AB  - Psoriasis, a T-cell-mediated disorder, affects 1% to 3% of the world's
      population. The characteristic lesions occur in many different forms, can cause
      significant discomfort and social distress, and in some instances, lead to
      dehydration and metabolic derangement. A chronic, unpredictable course and the
      necessity of periodically switching drugs or classes of drugs make psoriasis
      frustrating to treat. However, topical and systemic drug therapies and
      phototherapy can help minimize the exacerbations and prolong remissions. In this
      article, Dr Shenenberger outlines treatment approaches and discusses research
      into the use of immunomodulatory agents.

PMID- 15948364
TI  - Finding the correct inhaled corticosteroid dose in asthma.

PMID- 15948365
TI  - Urticaria and angioedema. Controlling acute episodes, coping with chronic cases.
AB  - Urticaria can be frustrating for patients and physicians alike. Its triggers may
      be medications, food allergies, insect stings, or physical stimuli and are often
      difficult to determine, especially when the urticaria has become chronic. In this
      article, Dr Varadarajulu gives an overview of both acute and chronic urticaria
      and the angioedema that accompanies it in about 40% of patients. She also
      outlines an approach to help evaluate and manage these common conditions.

PMID- 15948366
TI  - Recognizing drug allergy. How to differentiate true allergy from other adverse
      drug reactions.
AB  - Proper diagnosis of adverse drug reactions, although often complicated and
      difficult, is important for the patient and the physician. Often the question of
      whether it is safe to readminister a medication is an important clinical judgment
      that needs to be made. Alternative medications may be less effective or have
      greater toxicities or cost, or both. Areas of ongoing research to improve
      diagnostic precision for allergic drug reactions include further understanding of
      the immunochemistry of allergenic medications, improvement of the reproducibility
      and sensitivity of relevant in vitro assays, and further validation of computer
      assisted evaluation of adverse drug events. The positive and negative predictive
      values for these diagnostic tests need to be better defined whenever possible. At
      present, the primary diagnostic tool for properly assessing immunologic drug
      reactions remains a meticulous and detailed history obtained by an astute,
      knowledgeable, and motivated physician.

PMID- 15948367
TI  - Is ethnicity a factor in choice of antihypertensive drug?

PMID- 15948368
TI  - Anginalike pain and normal coronary arteries. Uncovering cardiac syndromes that
      mimic CAD.
AB  - Atherosclerotic CAD is the most common cause of cardiac chest pain in Western
      countries. Other cardiac syndromes may also cause anginalike pain and may be
      difficult to differentiate from atherosclerotic CAD. It is essential to make this
      distinction, because management and prognosis of these conditions are entirely
      different. A detailed history and, in some cases, special diagnostic methods can
      help make the diagnosis. When evaluating patients with anginalike chest pain and
      normal coronary arteries, physicians need to consider this group of diseases and
      tailor workup and diagnosis on an individual basis.

PMID- 15948370
TI  - Patient notes: Plantar warts.

PMID- 15948369
TI  - Is it Alzheimer's disease or something else? 10 disorders that may feature
      impaired memory and cognition.
AB  - Patients who have the classic combination of progressive memory loss and problems
      retrieving stored knowledge that is characteristic of Alzheimer's disease may
      actually have another, treatable disorder. In these cases, appropriate evaluation
      can reveal the true diagnosis and guide therapy to stabilize or improve thinking
      and avert other complications. In this article, Dr Barrett explores 10 conditions
      that may be mistaken for Alzheimer's disease.

PMID- 15948371
TI  - [Polymorphism in elderly hypertension].

PMID- 15948372
TI  - [Concept and clinical character of hypertension in the elderly].
AB  - Although blood pressure in the elderly was modulated by "physiological" changes
      due to aging, "pathological" changes in the elderly patients with essential
      hypertension cause to increase cardiovascular events and mortality. Hypertension
      in the elderly shows increase of pulse pressure, abnormal blood pressure daily
      profile and orthostatic hypotension. The importance of control of blood pressure
      in the elderly hypertensive patients is quite clear, however, the optimal blood
      pressure is still unclear. Very recently, clinical guideline of JSH 2004 by
      Japanese Society of Hypertension was published. We should try to control blood
      pressure in the elderly patients according to this guideline.

PMID- 15948373
TI  - [Epidemiology and prevention of elderly hypertension].
AB  - Our understandings about hypertension has increased as results of epidemiological
      programs issuing about preventions of cardiovascular disease, which started
      mostly in the latter half of 20th century and now it is known as the one of the
      most influencing risk factors of cardiovascular and cerebrovascular disease in
      the developed countries. We were able to get plenty information about the
      pathophysiology of hypertension and several randomized controlled trials were
      committed according to these information. Here we will discuss about the
      epidemiology of elderly hypertension.

PMID- 15948374
TI  - [Treatment of elderly hypertension based on various hypertension management
      guidelines--comparison between European and American guidelines and Japanese
      guidelines].
AB  - In civilized countries blood pressure is increased in association with age.
      Elderly population is lately increased both in Japan and Western countries and
      therefore elderly hypertensive patients are expected to increase. Recently,
      several guidelines and statements for the treatment of hypertension, such as JNC
      7, 2003 ESH/ESC, 2003 WHO/ISH, and BSH IV, are reported in Western countries. In
      Japan, Japanese Society of Hypertension reported guidelines for management of
      hypertension in 2000 (JSH 2000) and JSH 2000 is now revised and a new version was
      published at the end of 2004 (JSH 2004). In this article, management of
      hypertension (when starts the treatment, target blood pressure level, and choice
      of drugs, etc) in the elderly is described based on these guidelines and
      statements.

PMID- 15948375
TI  - [The Japanese Society of Hypertension Guidelines for the Management of
      Hypertension (JSH 2004)].
AB  - The essence of Japanese Society of Hypertension Guidelines for the Management of
      Hypertension (JSH 2000) was introduced. JSH 2004 is a revised edition of JSH
      2000. In JSH 2004, the significance of lifestyle modification is also emphasized
      as the basic treatment of hypertension, in which salt intake per day is reduced
      to below 6g/day. In drug therapy, Ca channel blockers, AII receptor blockers, ACE
      inhibitors, diuretics, beta -blockers and alpha-blockers are recommended as the
      main anti-hypertensive drugs. To obtain target blood pressure, a combined therapy
      of those drugs is recommended. In the management of aged hypertensive patients
      over 65, target blood pressure is generally below 140/90mmHg, but in those over
      75, transient target blood pressure is below 150/90 mmHg, if hypertension is
      moderate or severe.

PMID- 15948376
TI  - [Reduced arterial compliance with advancing age].
AB  - The term "compliance" is generally used as softness of the arterial wall.
      Fundamentally, compliance characterizes property of a chamber, being defined as
      deltaV/deltaP. It implies that how easily volume (V) of the chamber changes in
      response to unit pressure (P) change. However, in reality, the arterial system is
      not such a simple chamber but a complicated branched tubing system, in which
      compliance components are distributed along the tubing. It can be simplified as a
      single tube model, in which we can regard compliance as the sum of proximal
      portion as a determinant of characteristic impedance of the aorta and distal
      portion consisting of terminal impedance of the peripheral arterial bed. Such
      distributed model enables us to simulate pulse wave propagation and reflection,
      actually occurred in real arteries. This paper deals with parameters relating to
      arterial compliance corresponding to such distributed model. Arterial compliance
      is reduced with advancing age. This phenomenon has been widely recognized by
      epidemiological studies on blood pressure, in which systolic and pulse pressures
      are increased with aortic reflection without significant change in diastolic
      pressure. Also, many investigators reported age-dependent compliance declines by
      assessing compliance-relating parameters including cross-sectional compliance,
      pulse wave velocity and augmentation index. This reduced compliance may affect
      the heart as a pulsatile afterload and adversely alter myocardial energy balance.

PMID- 15948377
TI  - [Age related hemodynamic changes in the elderly].
AB  - Systolic blood pressure (SBP) increases by aging. In contrast, diastolic blood
      pressure (DBP) decreases after age 60 because of lowering aortic compliance.
      Therefore, isolated systolic hypertension (ISH) is common in the elderly. ISH is
      a risk for cardiovascular complications, and induces a left ventricular
      hypertrophy combined with diastolic dysfunction. Diastolic heart failure followed
      by diastolic dysfunction is more common than systolic heart failure in the
      elderly. Furthermore, changes in neuroendocrine systems by aging may lead
      orthostatic hypotension, non-dipping status, large blood pressure variability,
      and reduced heart rate variability. In the management of elderly hypertension,
      the understanding for these age-related hemodynamic changes is very important.

PMID- 15948378
TI  - [Aging of the autonomic nervous system].
AB  - Aging is associated with structural and functional changes in the autonomic
      nervous system (ANS), which innervates the whole body, and its altered function
      may influence almost all body systems. Changes related to aging are found in
      autonomic nerves and ganglia, and ANS controlled functions including
      cardiovascular functions. Much of the current knowledge about age-related changes
      in sympathetic nervous function is derived from studies of circulating
      catecholamine levels, norepinephrine kinetics and microneurographic recordings
      from sympathetic nerves of skeletal muscle. Significant evidence suggests that
      basal plasma noradrenaline levels increase with age. These data indicates that
      healthy aging is associated with elevated basal sympathetic nervous activity. In
      contrast, the reactivity of the sympathetic and the parasympathetic nervous
      activity are reduced with aging.

PMID- 15948379
TI  - [Aging and the endocrine system].
AB  - Blood pressure is maintained for preventing from the progression of damage of
      central nervous system. Endocrine system plays important roles in the prevention
      from the damage through the functional deviation. Hypertension is one of the
      results of the endocrinological deviation. Although the hypertension induced by
      the endocrinological deviation is a risk for the progression of metabolic
      syndrome, it is important in the maintaining activity of central nervous system.

PMID- 15948380
TI  - [Change of endothelial function with aging].
AB  - Vascular endothelium plays important roles in vascular relaxing, anti
      atherosclerotic, or anti-thrombotic effect through production of vasoactive
      substances such as nitric oxide. Accumulated evidences suggest that endothelial
      dysfunction is the initial step in the development of atherosclerosis. Recently,
      less invasive or non-invasive method such as venous occlusion plethysmography and
      measurement of flow-mediated dilatation has been developed to evaluate
      endothelial function. Several investigations using these methods showed that
      endothelial function is impaired with aging. The mechanism of endothelial
      dysfunction with aging remains to be fully elucidated, although oxidative stress
      may be involved in impairment of endothelial function.

PMID- 15948381
TI  - [Increasing oxidative stress in aging].
AB  - The balance between reactive oxigen species (ROS) production and degradation is
      important in defining oxidative stress. In aging process, ROS production
      increases and degradation is impaired and thus oxidative stress is accumulated.
      Oxidative stress damages organs both directly and indirectly. Protein, lipid, as
      well as DNA are directly react with ROS, more over, ROS interact with
      intracellular signaling system. It is reported that several transcription factors
      such as NF-kappaB, AP-1 and ASK-1 and also it interferes MAPK activity. Besides
      these signaling, we recently showed that insulin resistance is induced by
      accumulated oxidative stress in aged mice. Adrenomedullin deficient mice
      accumulate higher oxidative stress and insulin resistance developed in aging.
      Oxidative stress in aging relates not only direct organ damage but also induce
      risk factors for vascular damage such as metabolic syndrome.

PMID- 15948382
TI  - [Diagnostic criteria and diagnostic considerations for hypertension in the
      elderly].
AB  - Hypertension in the elderly consists mostly of essential hypertension, and its
      pathophysiology differs in many ways from that of essential hypertension in the
      young or middle-aged. No special diagnostic criteria for hypertension in the
      elderly were stated in ESH/ESC JNC 7 guidelines, that is, the criteria is
      systolic pressure of 140 mmHg and greater or diastolic pressure of 90mmHg and
      greater as in general adults. As the diagnostic considerations for hypertension
      in the elderly, we should pay much attention to medical history taking,
      measurement of blood pressure, discrepancy on auscultation, pseudohypertension,
      fluctuation of blood pressure, and diagnosis of secondary hypertension.

PMID- 15948383
TI  - [Clinical significance of home blood pressure measurements for diagnosis of
      hypertension in the elderly].
AB  - Systolic blood pressure elevates with increase in age. The frequency of white
      coat hypertension and masked hypertension also increase with increase in age.
      Elderly persons tend to have abnormal circadian rhythm of blood pressure. Home
      blood pressure measurements are very useful to determine such pathophysiological
      conditions. Home blood pressure is useful not only for diagnosis of hypertension
      but also for treatment and management of hypertension; i.e. choice and titration
      of antihypertensive drugs. A minimal antihypertensive effect and duration of
      action of antihypertensive drugs are determined by home blood pressure
      measurements: the latter is established by the comparison of the antihypertensive
      effect of the drug in the morning with that in the evening, i.e. morning-evening
      ratio (ME ratio).

PMID- 15948384
TI  - [Non-pharmacological treatment of hypertension in the elderly].
AB  - We reviewed non-pharmacological treatment of hypertension in the elderly.
      Although hypotensive effect of salt restriction was evident, severe salt
      restriction might result in impairment of QOL by decrease in appetite and
      consequent nutritional deterioration. Hypotensive effect of mild to moderate
      aerobic exercise was also evident. Our previous report indicated that decrease in
      blood pressure was less in older subjects than in younger group. Another study
      showed that blood pressure decreased even during 3 to 9 months after the
      beginning of exercise therapy. These findings might indicate that decrease in
      blood pressure in the elderly was slower than in younger subjects.

PMID- 15948385
TI  - [Guidelines for antihypertensive treatment of elderly hypertensive patients
      without complications based on EBM].
AB  - Hypertension is one of the most significant risk factors for cerebrovascular and
      heart diseases, which rank as the second and third most frequent causes of death
      in Japan, respectively. The prevalence of hypertension rises as the population
      grows older, affecting approximately 60% of the Japanese aged 65 yr or older, and
      there are currently more patients receiving treatment for hypertension than for
      any other disease in Japan. As the size of the elderly populations in our country
      continuously increases rapidly, hypertension has become one of the most important
      diseases to be treated. Based on the results of numerous clinical intervention
      trials, treatment of hypertension in the elderly, including treatment of systolic
      hypertension, has generally been of great benefit. However, the efficacy of
      treatment of so-called very old hypertensive patients aged 85 yr or older is
      still controversial. Recently, Guidelines for the Management of Hypertension of
      Japanese Society of Hypertension (JSH 2004) has been reported, which are based on
      evidence-based medicine(EBM), adopting the results of mega-trials in Japan and in
      Western countries, but also considering the lifestyle of Japanese. This paper
      explaines the part of "Antihypertensive Treatment of Elderly Hypertensive
      Patients without Complications" in the Guidelines.

PMID- 15948386
TI  - [Management of hypertension in elderly patients with stroke].
AB  - Hypertension is the most significant risk factor for stroke. Recently, many mega
      studies have been shown that antihypertensive therapy reduced the incidence of
      stroke not only for normal elderly but also for patients with a past history of
      stroke. To prevent the recurrences of stroke, tighter control of blood pressure
      is thought to be required than used to be. According to the recent Japanese
      guidelines for hypertension, desirable blood pressure should be 140/90 mmHg or
      less for the patients with stroke.

PMID- 15948387
TI  - [Treatment of hypertension in elderly patients with coronary heart disease].
AB  - Many clinical trials have been conducted to prevent cardiovascular complications
      and reduce mortality in hypertensive patients. Undoubted, but limited effects of
      beta-blocker and diuretic antihypertensive drugs had been established. Although
      angiotensin-converting enzyme inhibitor and angiotensin II receptor antagonist
      lowered the incidence of events and mortality less than classical
      antihypertensive drugs, recent studies revealed that prompt and enough lowering
      the blood pressure is more important than choosing the types of drugs.

PMID- 15948388
TI  - [Heart failure in hypertension in the elderly].
AB  - Incidence and prevalence of heart failure, in the form of systolic or diastolic
      ventricular dysfunction, are particularly common in elderly patients with
      hypertension. The importance of treating hypertension in the elderly as a means
      of preventing chronic heart failure was emphasized by recent trials including
      meta-analysis. Fastidious blood pressure control by angiotensin-converting enzyme
      inhibitors and angiotensin-II receptor antagonists along with low-doses diuretics
      as first-line therapy is recommended. However, many elderly patients with
      hypertension have other risk factors, target organ damages and associated
      cardiovascular conditions, to which the choice of the first drug should be
      tailored. In such cases, beta blockers, aldosterone blockers and long-acting Ca
      antagonists are also recommended.

PMID- 15948389
TI  - [Treatment for the elderly hypertensive patient with renal insufficiency].
AB  - The guideline of Japanese Society of Hypertension in 2004 was opened in the early
      January in 2005. This recommends that blood pressure of the elderly people with
      hypertension should be lower as well as that of the young subjects. However,
      unfortunately, this does not mention how much lower blood pressure of the elderly
      hypertensive patients with renal insufficiency is. Our group has proposed the
      combination therapy with a low dose of more than 2 antihypertensive drugs to
      reduce blood pressure of these subjects in order to avoid adverse effects of
      antihypertensive agents. As the combination therapy, drugs with inhibition of the
      renin-angiotensin system such as ACE inhibitor or angiotensin receptor blocker
      and a calcium antagonist or diuretics are suggested.

PMID- 15948390
TI  - [Management of hypertension with diabetes mellitus in the elderly].
AB  - The number of an elderly patient who has hypertension with diabetes mellitus has
      been increasing year by year since the life style of people has become
      Americanized in our country. Metabolic syndrome is characterized by hypertension,
      dyslipidemia, central adiposity and insulin resistance. It is recently recognized
      as the high risk for the macrovascular disease such as cerebral infarction and
      acute myocardial infarction. In diabetic patients, to prevent the life
      threatening event or slow complications intensive blood pressure control is as
      efficacious as good glycemic control. The optimal blood pressure level to reduce
      hypertension-related morbidity and mortality in diabetic elderly has been
      proposed 130/80 mmHg in JSH 2004. The blood pressure level in the elderly should
      be lowered very slowly with careful monitoring of systemic ischemia. Early use of
      antihypertensive drug combinations is gaining favor. As the first step therapy
      would be recommended angiotensin receptor blocker, angiotensin-converting enzyme
      inhibitor and sustained release calcium channel blocker. Especially in the
      elderly, good control of life-style related diseases would be achieved through a
      team effort comprising the clinician, psychologist, nurse, pharmacologist,
      dietitian, other professionals and the patient's family. Comprehensive geriatric
      assessment can facilitate the maintenance of drug compliance for well control of
      blood pressure level.

PMID- 15948391
TI  - [Management of elderly hypertensive individuals with hyperlipidemia].
AB  - Elderly people with hypertension and hyperlipidemia are regarded as high-risk
      patients and are supposed to be treated with appropriate drugs. From the evidence
      of clinical trials, renin-angiotensin system inhibitors and calcium channel
      blockers would be the first choices, and the combination therapy with diuretics
      or alpha-blockers would be the next choice. However, since the effect of anti
      hypertensive drugs on plasma lipids is much less than that of the lipid-lowering
      drugs, anti-hypertensive drugs should be chosen in consideration of the patient's
      complicated diseases, because elderly people are often affected with other more
      serious complications such as ischemic heart disease, cerebrovascular disease,
      renal dysfunction, and chronic lung disease. If hyperlipidemia remains after anti
      hypertensive drugs are used, the use of lipid-lowering drugs such as statins is
      recommended.

PMID- 15948392
TI  - [Future medicine for hypertension in the elderly].
AB  - The number of the aged patients with hypertension is now explosively increasing.
      In near future, progress of new and tailor-made prescribed antihypertensive drugs
      and curable-gene therapy for hypertension will improve new era of hypertension in
      the elderly. And finally, resolusion of the aging mechanism and anti-aging
      medicine may open our future.

PMID- 15948393
TI  - [Intervention trials for elderly hypertension in Western countries].
AB  - Many large-scale intervention trials performed in Western countries have proven
      the necessity of treatment of hypertension in the elderly, including isolated
      systolic hypertension. However, it is still unclear the benefit of
      antihypertensive treatment in mild hypertensive patients and that in very elderly
      patients with hypertension. An ongoing clinical trial, the Hypertension in the
      Very Elderly Trial (HYVET), may clarify whether or not antihypertensive treatment
      is beneficial in the very elderly. Regarding target blood pressure, there is no
      clinical study in which average of systolic blood pressure at the end of study
      decreased lower than 140 mmHg. Regarding the first-line drugs for elderly
      hypertension, usefulness of diuretics and calcium channel blockers has been
      demonstrated in studies with placebo control group. Usefulness of inhibitors of
      the rennin-angiotensin system has been also reported in LIFE substudy and ANBP2.
      It is still required to perform large scale trials in the elderly hypertension to
      answer these undissolved problems.

PMID- 15948394
TI  - [Intervention studies on elderly hypertensive patients in Japan].
AB  - Considerable evidence of the usefulness of antihypertensive therapy in elderly
      hypertensive patients has been shown by the clinical intervention studies in
      western countries, using diuretics, beta-blockers, Ca antagonist, angiotensin
      converting enzyme inhibitors and angiotensin II receptor blockers. Only two
      intervention studies on elderly hypertensive patients, which are NICS-EH and
      JATE, have been reported in Japan. Several Japanese intervention studies, such as
      JATOS, COPE, CASE-J, HOMED-BP and VALISH which conducted recently will provide us
      with new evidence in elderly hypertensive patients. We summarize the content of
      intervention studies on elderly hypertensive patients in western countries and
      Japan.

PMID- 15948395
TI  - [Therapeutic strategy for morning blood pressure elevation in elderly
      hypertensives].
AB  - Although the cardiovascular events such as stroke, angina pectoris and myocardial
      infarction can occur at any time of day, it has been known that the peak
      incidence of the cardiovascular events increases during the morning period. In
      elderly hypertensives, a greater morning blood pressure surge is associated with
      an advanced silent cerebrovascular disease as well as a higher incidence of
      stroke. Thus, the blood pressure control of the early morning period may become
      an important therapeutic strategy for preventing the cardiovascular events. In
      this review, we focused on the recent strategy for morning blood pressure rising
      in the elderly hypertensives.

PMID- 15948396
TI  - [Clinical characteristic of secondary hypertension in the elderly].
AB  - The prevalence of secondary hypertension is higher in the elderly population.
      Renal hypertension is the most prevalent. The prevalence of renovascular
      hypertension (RVH) increases with age. Since RVH in the elderly is frequently
      associated with systemic atherosclerosis, other atherosclerotic disorders
      including ischemic heart disease need to be evaluated. The prevalence of primary
      aldosteronism and Cushing's syndrome decreases with age, while that of
      pheochromocytoma persists in the elderly population. Due to lack of classical
      symptoms, special attention should be paid to find pheochromocytoma in the
      elderly.

PMID- 15948397
TI  - [Treatment of hypertension in the elderly and its effects on the QOL].
AB  - Elderly patients have much more complex QOL problems as compared with young or
      middle-aged patients because of their specific social and psychological
      circumstances, as well as their multiple organ disorders. Specifically, one
      should take into account, in the treatment of hypertension in the elderly with
      respect to QOL, the effect of antihypertensive drugs on the cognitive function
      and the influence on other diseases or hypertensive complications. Most of the
      currently used antihypertensive drugs are shown to be inert to the cognitive
      function. In order to maintain or improve QOL of elderly hypertensive patients,
      adequate drugs should be selected individually. In general, ACE inhibitors, long
      acting Ca antagonists are the drugs of choice for the treatment of hypertension
      in the elderly with regard to QOL.

PMID- 15948398
TI  - [WT1 peptide-based immunotherapy].
AB  - The Wilms' tumor gene WT1 is overexpressed in leukemia and various types of solid
      cancers and its product is a tumor rejection antigen. A phase I clinical trials
      of WT1 peptide-based cancer immunotherapy were performed with good clinical
      response but with only skin reaction at the injection sites of WT1 vaccine. Thus,
      WT1-targeting immunotherapy should be promissing.

PMID- 15948399
TI  - [Motor neuron disease up-to date].

PMID- 15948400
TI  - [Neuroimaging in posttraumatic stress disorder].

PMID- 15948401
TI  - [Sleep disturbance and sleep disorders: the methodology of diagnosis and
      treatment].

PMID- 15948402
TI  - [A hypnotic drug for sleep disturbances in patients with Parkinson's disease].
AB  - Patients with Parkinson's disease have been known to have sleep disturbances of
      various types. Zolpidem tartrate, an imidazopyrimidine short-acting hypnotic drug
      used treat insominia and several patients with PD have described a significant
      improvement of parkinsonian symptoms after administration of zolpidem tartrate.
      We tried to evaluate effect of zolpidem tartrate for sleep disturbances in
      patients with PD by a Japanese version of Chaudhuri's Parkinson's disease Sleep
      Scale (PDSS) and Unified Parkinson's disease rating Scale (UPDRS) motor scale.
      Twelve patients with PD (mean age 67.4 years old, range 40-77 years old) were
      evaluated by PDSS and UPDRS before and two weeks after prescribed zolpidem
      tartrate 5 mg per day. Patients showed improvement in items relating overall
      sleep disturbances, sleep refreshment and morning stiffness. Disabilities
      remained unchanged before and two weeks after prescribing zolipdem tartrate.
      Zolpidem tartrate may be useful for sleep disturbances in patients with PD and
      for improving their quality of daily livings.

PMID- 15948403
TI  - [Significance of shunt efficacy decision of SPECT on idiopathic normal pressure
      hydrocephalus].
AB  - PURPOSE: The purpose of this study was to investigate the significance of the
      shunt-effect evaluation of SPECT in idiopathic normal pressure hydrocephalus
      (iNPH). SUBJECTS AND METHODS: The subjects were 15 patients with possible iNPH,
      aged 62-83 (mean 75.3, the ratio of males to females to 6:9), who were treated at
      our department during the period from June to September, 2004. All patients
      received the lumbar tap test (LTT) at the outpatient section before surgery. An L
      P shunt was conducted on patients whose the LTT positive or negative with
      cerebrospinal fluid outflow resistance value (Ro) was 10 mmHg/ml/min. or higher
      patients. As for SPECT, a 3D-SSP Z-score, as well as an mCBF, was conducted
      before and after the LTT and within one month after surgery. Comparisons were
      made for (1) the shunt effect, (2) mCBF before and after the LTT and after
      surgery, (3) mean cerebral blood flow increase rate (mIR) after the LTT, and (4)
      3D-SSP before and after surgery. RESULTS: (1) The shunt was effective for all the
      patients. (2) The mCBF levels was 30.8 +/- 4.02 ml/100 g/min. before the LTT,
      37.1 +/- 100 g/min. after the LTT, and 38.6 +/- 3.4 ml/100 g/min. after surgery.
      A significant increase in mCBF was observed both after the LTT and after surgery
      (p < 0.05). (3) The mean mIR after the LTT was 21.2 +/- 8.01%, with all the
      patients showing 10% or higher. (4) The ischemic patterns in the SD-SSP Z-score
      before surgery were the frontal type (F: 10 cases, 66.7%), the occipitotemporal
      type (OT: 3 cases, 20%), and the mixed type (M: 2 cases, 13.3%), but not the
      parietal localized type. The post-operative course showed no-change in 4 cases,
      disappearance-reduction in 9 cases, and shift to OT in 2 cases. CONCLUSION: The
      evaluation factors in the measurement of the cerebral blood flow for evaluation
      of the shunt effect were the following two items. (1) The mIR of mCBF after the
      LIT was 10% or higher. (2) As for the preoperative cerebral ischemic patterns,
      there were many F cases and no parietial localized types found.

PMID- 15948404
TI  - [Tooth loss and the incidence of ischemic stroke].
AB  - Chronic infectious diseases may increase the risk of stroke. We investigated
      whether periodontal disease was a risk factor for cerebral ischemia. A case
      control study with 444 stroke patients, 194 hemorrhagic patients and 250 ischemic
      patients, and 164 hospital controls with nonvascular and noninflammatory
      neurological diseases, was performed. All subjects were evaluated by either a CT
      scan or MRI and their number of teeth was determined. The number of teeth in the
      patients with cerebral ischemia was found to be significantly fewer than for the
      cerebral hemorrhage group and a control group between 40 and 65 years of age. The
      degree of tooth loss was particularly remarkable in patients with
      atherothrombotic and cardioembolic brain infarction. As a result, tooth loss
      following severe periodontal disease may therefore be a risk factor for the onset
      of cerebral infarction in some patients.

PMID- 15948405
TI  - [A case of multiple brain abscess effectively markedly responded to high dose
      panipenem/betamipron administration].
AB  - A 54-year-old, previously healthy female experienced headache, nausea and
      vomiting, and consulted our hospital regarding her symptoms. Her cerebrospinal
      fluid (CSF) showed leukocytosis with polymorphonucleosis and hypoglycemia, thus
      she was diagnosed with bacterial. She admitted to our hospital and combination
      therapy of ampicillin and cefotaxime was started. CSF and blood cultures was
      negative. On the third hospital day, despite a decrease in her CSF cell count,
      her consciousness level decreased and neck stiffness worsened. On the seventh
      hospital day, the CSF cell count increased again, and we changed antibiotics to
      panipenem/betamipron (PAPM/BP) at 4 g/day. On the tenth hospital day, the CSF
      cell count decreased, but by the twelfth hospital day her consciousness had
      deteriorated to a drowsy state. Brain CT and MRI revealed multiple brain
      abscesses and hydrocephalus. We increased the dose of PAPM/BP up to 8 g/day, and
      her neurological, CSF and brain MRI findings subsequently improved. The patient
      was discharged from our hospital on the sixty-ninth hospital day. As the
      frequency of beta-lactamase-producing bacteria is currently increasing,
      carbapenems should be considered as first choice of antibiotics for the initial
      treatment of multiple brain abscess.

PMID- 15948406
TI  - [A case of 53-years-old woman with the onset of subacute right-sided numbness,
      and presented with various lesions on MRI].

PMID- 15948407
TI  - [Comparison of value of free-to total prostate specific antigen, prostate
      specific antigen density and prostate specific antigen density of transition zone
      for diagnosis of prostate cancer in patients with a PSA level of 4.1-10 ng/ml].
AB  - PURPOSE: We evaluated the utility of free-to total PSA (F/T PSA) ratio, PSA
      density (PSAD) and PSA density of the transition zone (PSATZ) in diagnosis of
      prostate cancer with intermediate PSA level (4.1-10 ng/ml). PATIENTS AND METHODS:
      Between January 2000 and December 2003, systematic prostate biopsies were
      performed on 178 patients with intermediate PSA level. The clinical values of F/T
      PSA ratio, PSAD and PSATZ for the detection of prostate cancer were compared by
      using receiver operating characteristic (ROC) curves. RESULTS: Overall, 57 of the
      178 (32%) patients had prostate carcinoma. The ROC curve analysis showed PSAD and
      PSATZ were superior to F/T PSA ratio in patients with intermediate PSA level. In
      patients with total prostate volume greater than 30 cm3, the area under the ROC
      curve for F/T PSA ratio was greater than that for PSAD and PSATZ. CONCLUSIONS:
      PSAD and PSATZ were more powerful predictors of prostate cancer than F/T PSA
      ratio in patients with intermediate PSA level. While F/T PSA ratio was effective
      for diagnosis of prostate cancer in prostate volume greater than 30 cm3.

PMID- 15948408
TI  - [Predictive factors associated with successful varicocele repair a study of 139
      infertile men with valicocele].
AB  - PURPOSE: To determine pretreatment parameters which predict improvements
      following varicocele repaire in semen quality. MATERIALS AND METHODS: We
      retrospectively evaluated a total of 139 infertile patients who underwent
      varicocelectomy from February 1995 to March 2000. A logistic regression analysis
      was performed to identify parameters associated with improvements in semen
      quality. Parameters evaluated included varicocele grade, age, testicular volume,
      serum testosterone, liteinizing hormone (LH), follicle-stimulating hormone (FSH),
      preoperative sperm density and sperm motility. RESULTS: Of 139 patients 71
      (51.0%) improved sperm concentration and 59 (42.4%) improved sperm motility
      postoperatively. Overall, median sperm density significantly increased from 10 x
      10(6)/ml preoperatively to 30 x 10(6)/ml postoperatively. Sperm motility also
      significantly increased 33% to 45%. In logistic regression analysis, varicocele
      grade (odds ratio [OR] = 5.7; 95% confidential interval [CI : 1.9-17), FSH level
      ([OR] = 0.76; [CI]: 0.60-0.96) and sperm motility ([OR] = 1.03; [CI]: 1.0-1.1)
      were independent predictive factors for improvement in sperm concentration.
      CONCLUSION: Varicocelectomy improves sperm concentration and motility. Our data
      suggest that patients with grade 3 varicocele, low serum FSH level and high sperm
      motility are more likely to benefit from varicocele repair in sperm
      concentration.

PMID- 15948409
TI  - [Evaluation of the crystal inhibitory effect of angiotensin II type I receptor
      blocker in etylene glycol treated rat kidney].
AB  - PURPOSE: We examined whether there would be any inhibitive effect to the crystal
      formation in ethylene glycol treated rat kidney by angiotensin II type I receptor
      blocker (candesartan). METHODS: We divided 10-weeks-old male Sprague-Dawley rats
      into 4 groups. In these groups, rats were given tap water (group A), 1.0%
      ethylene glycol (group B), 1.0% ethylene glycol and 20 microg/ml candesartan
      (group C), 20 microg/ml candesartan (group D) for 4 weeks. Immunohistochemical
      studies of a renal tissue was performed by ED1 antibody and the osteopontin
      antibody, the transcription of renin, angiotensin converting enzyme, angiotensin
      II and osteopontin mRNA in whole kidney was determined using real time PCR and
      malondialdehyde level was measured. Renal tissue was evaluated using H.E. stain
      for counting the calcium deposit in the renal tubules. Calcium concentrations in
      whole kidney were measured with an atomic absorption spectrophotometer. RESULTS:
      Although there is no significant difference urinary oxalate and calcium levels
      compared with group B and C, group C showed fewer the numbers of calcium deposit
      in the tubules and decreased the amount of calcium contained in the whole kidney,
      ED1 positive cells, osteopontine mRNA expression and malondialdehyde level.
      CONCLUSION: These results suggest that candesartan inhibited superfluously
      induced osteopontin in the whole kidney by ethylene glycol and crystal formation
      was also related decreased.

PMID- 15948410
TI  - [Health-related quality of life after radical prostatectomy or radiotherapy].
AB  - PURPOSE: We compared general and disease specific health related quality of life
      (QOL) after surgery and radiotherapy for prostate cancer. MATERIALS AND METHODS:
      We performed a retrospective survey of patients treated between 1992 and 2001.
      General and disease specific health related QOL were assessed by the SF-36 and
      the University of California-Los Angels Prostate Cancer Index (UCLA PCI). We
      mailed questionnaires of QOL survey and obtained from 143 and 73 men who treated
      surgery and radiotherapy. The median ages of surgery and radiation group were
      70.9 and 79.2 years old, and the median periods after treatment were 2.7 and 2.0
      years, respectively. RESULTS: Physical function, role physical, social
      functioning and mental health were higher score in surgery group than radiation
      group, however, general health perceptions was higher in radiation group among SF
      36. Surgery group had worse urinary function and better sexual function compared
      with radiation group. Multi-variable analysis showed that scores of social
      functioning, mental health and sexual function were most influenced by each
      modality, the scores of physical function, role physical, urinary function and
      sexual bother were most influenced by age, and the score of general health
      perceptions and body pain was most influenced by the existence of recurrence.
      CONSIDERATION: This cross-sectional survey cleared the differences of QOL after
      surgery and radiotherapy, and the influences of each modality. However, because
      of difference in background of each group, longitudinal investigation will need
      to aid patients in the decision making process.

PMID- 15948411
TI  - [Primary, nonviral, hepatocellular carcinoma in patients with prostate cancer
      treated by hormone therapy: 2 case reports].
AB  - We studied two cases of primary, hepatocellular carcinoma (HCC) that occurred
      following hormone therapy (estrogen therapy in one case and total androgen
      blockade therapy in another) for stage D2 prostate cancer. Prostate cancer is
      considered to be hormone-dependent, and androgens appear to be important hormonal
      factors. However, hepatocellular carcinoma has been shown to have both estrogen
      and androgen receptors, suggesting that this may be dependent on estrogen or
      androgen. Reported here are two unique cases of hepatocellular carcinoma in
      patients with prostate cancer; the pathogenesis of HCC in these patients was
      suspected to be related to diethylstilbestrol (DES) therapy and antiandrogen
      therapy for their prostate cancer.

PMID- 15948412
TI  - [A case of prostate cancer diagnosed pathologically by bone metastatic site
      biopsy].
AB  - A 61-year-old man consulted our hospital complaining of high prostate specific
      antigen (PSA) value and difficulty to urinate. Prostate biopsy had been performed
      at another hospital, but did not reveal cancer. PSA was 18.5 ng/ml. Transrectal
      ultrasound-guided prostate biopsy was performed, but cancer was not detected.
      Later, PSA rose rapidly, and findings suggesting bone metastasis at right pubic
      bone and left sacro-ilial joint were found on computed tomography (CT), bone
      scintigraphy and magnetic resonance imaging (MRI). A repeat prostate biopsy was
      performed, but cancer was not detected from the prostate. On right pubic bone
      biopsy, poorly to moderately differentiated adenocarcinoma was detected. PSA
      immunohistochemical staining was positive, and the diagnosis was bone metastasis
      from prostate cancer. After endocrine therapy was started, PSA declined and bone
      metastasis disappeared on bone scintigraphy.

PMID- 15948413
TI  - [The effect of botulinum toxin injection into the bladder for overactive bladder:
      two case].
AB  - Two cases of intractable overactive bladder which were treated by intradetrusor
      botulinum-A toxin (BTX-A) are presented. Case 1: A 53-year-old woman suffered
      from adhesive arachinoiditis. She had severe detrusor hyperreflexia and urge
      urinary incontinence despite a high dose of anticholinergic medication. Under
      cystoscopic control, a total of 300 units of BTX-A were injected into the
      detrusor muscle at 30 sites (10 units per ml per site), sparing the trigone area
      using a 27G flexible injection needle. This procedure was done under both caudal
      anesthesia with 10 ml 1% lidocaine and bladder mucosa anesthesia by instilling 40
      ml 2% lidocaine. At a 12-week followup she was completely continent. Case 2: A 63
      year-old man with intractable detrusor overactivity of idiopathic origin was
      treated using the above technique. Urge urinary incontinence decreased 4 weeks
      after the BTX-A injections. However, postvoid residual urine volume was
      increased, and intermittent self-catheterization was needed. Intradetrusor BTX-A
      dramatically increases the bladder capacity and decreases the frequency of urge
      urinary incontinence. However, this treatment caused urinary retention in Case 2.
      We believe that the dosage amount of BTX-A should be changed case by case.

PMID- 15948414
TI  - [A case of uretero-aortic fistula after the urinary diversion].
AB  - We report a case of a patient with a fistula between left ureter and abdominal
      aorta. The patient was a 84-year-old male who had undergone total cystectomy with
      a single stoma cutaneous ureterostomy for the treatment of transitional cell
      carcinoma of the bladder. His postoperative course was complicated by stenosis of
      the stomal orifices, which was treated with two silicone tubes. Twelve years
      after the operation, massive arterial bleeding occurred from the cutaneous
      ureterostomy, which was caused by left ureteral-abdominal aortic aneurysm fistula
      due to prolonged ureteral stenting. Graft replacement for abdominal aortic
      aneurysm and percutaneous left nephrostomy were performed, but he died 3 months
      following the operation due to multiple organ failure. Ureteroarterial fistula
      after the urinary diversion can occur in association with prolonged ureteral
      stenting, radiation therapy, and vascular pathology. Identification of a fistula
      is often difficult and requires the physician to be highly alert and vigilant.

PMID- 15948415
TI  - [Current topics in cataract and intraocular lens implant surgery].

PMID- 15948416
TI  - [Effects of surface modification of intraocular lenses on foreign body reaction
      ].
AB  - PURPOSE: In order to improve biocompatibility, we investigated the effects of
      surface modification by 2-methacryloyloxyethyl phosphorylcholine (MPC) on the
      foreign body reaction of intraocular lens (IOLs). MATERIALS AND METHODS:
      Materials of the IOLs were polymethylmethacrylate, hydrophobic acryl, and MPC
      surface-modified hydrophobic IOLs (MPC modified acryl). In an in vitro study,
      cultured macrophages sampled from mouse intra-abdominal exudate were cultured on
      a plate for each IOL material. The cell density and morphology of attached cells
      on the IOL materials were investigated. In an in vivo study, each IOL material
      was implanted in the peritoneal space of mice and foreign body reaction was
      investigated with a light microscope and a scanning electron microscope. RESULTS:
      In the in vitro study, the cells on the MPC modified acryl IOL material were
      remarkably fewer than those on the plates of the other two IOL materials.
      Regarding the implanted IOL matrevials, MPC modified acryl IOL material showed
      more polynuclear giant foreign body cells in the early period than the other two
      IOL materials. CONCLUSION: MPC surface modification can reduce the foreign body
      reaction of IOLs and has the potential to improve biocompatibility of IOL
      materials.

PMID- 15948417
TI  - [Study of change of size of the punctum before insertion and after extrusion of a
      punctal plug and selection of an appropriate plug for reinsertion].
AB  - PURPOSE: In cases when the reinsertion of punctal plugs is considered,
      enlargement of the punctum is often experienced and a larger punctal plug is
      sometimes required for reinsertion. We therefore investigated the change in the
      size of the punctum before insertion and after extrusion of a punctal plug and
      the selection of an appropriate punctal plug for reinsertion. SUBJECTS AND
      METHODS: There were 70 cases where punctal plugs were reinserted (37 eyes from 32
      patients) because of extrusion of the plugs. A retrospective study was performed
      with regard to the change in the size of the punctum before insertion and after
      extrusion of the punctal plugs, and with regard to the type of plug reinserted.
      RESULTS: There were significant changes in the size of the punctum before
      insertion [0.70 +/- 0.09 (mean +/- standard deviation) mm] and after extrusion
      (0.78 +/- 0.07 mm) of the punctal plug (p < 0.001). In 22 cases of 23 cases which
      experienced extrusion of the 0.8 mm Eagle plug (EP; Eagle Vision), Punctal plugs
      (PP; FCI) of M size were selected for reinsertion, because there are no EPs
      larger than 0.8 mm available for reinsertion. DISCUSSION: After extrusion of the
      punctal plug, the punctum is likely to be enlarged, resulting in the need to
      select a larger punctal plug. Therefore, cases which experienced extrusion of an
      EP were likely to eventually have the EP replaced by a PP during follow-up
      treatment.

PMID- 15948418
TI  - [Automatic pulse system for conducting ultrasonic cataract operation].
AB  - PURPOSE: For use in phacoemulsification and aspiration (PEA) with a high
      frequency pulse sytem, we invented an Automated Pulse System(APS) in which the
      ultrasonic energy level and the percentage of ultrasonic pulses per second are
      regulated by a foot-pedal and suotion mechanism. METHOD: We compared the APS and
      the conventional continuous ultrasonic system experimentally by inserting a
      cataract model in an extracted aphakic pig eye. RESULT: Ultrasonic use time was
      not significantly different between the two methods. Gross ultrasonic energy and
      operation time were significantly decreased in the APS method (p < 0.05).
      CONCLUSION: Automatically, APS increases ultrasonic frequency and the percentage
      of ultrasonic pulses in nuclear emulsification. APS is an effective way to reduce
      the utilization of ultrasonic energy in the pulse mode without complicated foot
      pedal control.

PMID- 15948419
TI  - [Characteristics of filtering blebs after fornix-based trabeculectomy with a
      scleral tunnel].
AB  - PURPOSE: To evaluate the characteristics of filtering blebs after fornix-based
      trabeculectomy with a scleral tunnel. PATIENTS AND METHODS: We studied 119 eyes
      of 149 patients who had undergone fornix-based trabeculectomy with mitomycin C as
      their primary surgery between 2000 and 2002 and in whom we could evaluate the
      characteristics of filtering blebs after a follow-up period of 6 months or more,
      and whose intraocular pressure at the evaluation time was 18 mmHg or less. We
      evaluated the width, depth, height, border, avascular area, conjunctival
      thickness, and late-onset bleb leak of the filtering blebs. RESULTS: The mean
      period of evaluation was 528 +/- 243 days (mean +/- standard deviation) after
      surgery, and the mean intraocular pressure at that time was 12.0 +/- 3.0 mmHg.
      Among these patients, 108 eyes (72.5%) had completely diffuse blebs and 90 eyes
      (60.4%) had completely vascular blebs. There was no apparent late-onset bleb
      leak. CONCLUSION: Fornix-based trabeculectomy with a scleral tunnel appears to be
      an effective method of developing diffuse, vascular and safe blebs with a low
      risk of late-onset bleb leak.

PMID- 15948420
TI  - [Case of eyelid nodular fasciitis in which magnetic resonance imaging was useful
      for clinical diagnosis].
AB  - BACKGROUND: Magnetic resonance imaging (MRI) is useful in pathogenesis,
      diagnosis, and treatment. CASE: A 70-year-old man. He noticed that the right side
      of his upper lid had swollen 3 weeks previously. No abnormal findings were
      recognized in visual acuity, intraocular pressure, anterior segment, lens,
      vitreous, or fundus. From MRI findings 10 days after his first visit, dermoid
      cyst, soft tissue tumor, and nodular fasciitis were suspected. Because MRI 2
      months after the first visit showed a decrease in tumor size, soft tissue tumor
      was ruled out. Finally histopathological examination revealed nodular fasciitis,
      although the findings during the operation did not differentiate between dermoid
      cyst and nodular fasciitis. CONCLUSION: MRI at different intervals was useful for
      clinical diagnosis.

PMID- 15948421
TI  - Congenital and hereditary ocular abnormalities in cats.
AB  - Congenital and inherited ocular diseases are reported less frequently in the cat
      than the dog. The 2 species also differ in their array of disorders, with
      familiar canine abnormalities like cataracts overshadowed by unique feline
      diseases such as eyelid agenesis and corneal sequestration. Organized according
      to the primary ocular structure affected and commingling congenital and inherited
      disorders in each section, the review begins with multiple ocular anomalies and
      their impact on globe-orbit relationship. Adnexal disorders include eyelid
      agenesis, entropion, dermoid, and nictitans gland protrusion. Corneal
      abnormalities range from the routine sequestrum and PPM-related opacity to those
      rare infiltrates accompanying inborn errors of metabolism. Brief descriptions of
      uveal anomalies, primary glaucoma, cataracts, and lens luxations follow. Retinal
      dysplasia and progressive retinal atrophy complete the summary. Suspicions of
      heritability are often based on small numbers of animals in sporadic reports of
      ocular disease, but the Persian, Burmese, and Siamese are among the breeds
      repeatedly linked with one or more of these disorders.

PMID- 15948422
TI  - Feline corneal disease.
AB  - The cornea is naturally transparent. Anything that interferes with the cornea's
      stromal architecture, contributes to blood vessel migration, increases corneal
      pigmentation, or predisposes to corneal edema, disrupts the corneas transparency
      and indicates corneal disease. The color, location, and shape and pattern of a
      corneal lesion can help in determining the underlying cause for the disease.
      Corneal disease is typically divided into congenital or acquired disorders.
      Congenital disorders, such as corneal dermoids are rare in cats, whereas acquired
      corneal disease associated with nonulcerative or ulcerative keratitis is common.
      Primary ocular disease, such as tear film instability, adenexal disease (medial
      canthal entropion, lagophthalmus, eyelid agenesis), and herpes keratitis are
      associated with the majority of acquired corneal disease in cats.
      Proliferative/eosinophilic keratitis, acute bullous keratopathy, and Florida
      keratopathy are common feline nonulcerative disorders. Nonprogressive ulcerative
      disease in cats, such as chronic corneal epithelial defects and corneal
      sequestration are more common than progressive corneal ulcerations.

PMID- 15948423
TI  - Update on pathogenesis, diagnosis, and treatment of feline herpesvirus type 1.
AB  - Feline herpesvirus type 1 (FHV-1) infection, but not necessarily chronic or
      recurrent disease, is common throughout domestic cat populations worldwide.
      Knowledge of a few essential virological facts permits practitioners to provide
      appropriate advice to owners of individual pet cats infected with this virus and
      to assist in the management of shelters and other multicat households in which
      the virus is enzootic. This article discusses pathogenesis, diagnostic
      techniques, and clinical signs considered characteristic of infection with FHV-1.
      Treatment options are considered under the broad categories of supportive care,
      antiviral agents, and adjunctive therapies.

PMID- 15948424
TI  - Feline lens disorders.
AB  - The lens is the second most powerful structure for refraction in the eye, and is
      important in the fine-focusing ability in individual species. Specific disorders
      of the feline lens are frequent in clinical practice and include: congenital
      anomalies, nuclear sclerosis, cataracts, lens subluxations and luxations,
      intraocular sarcomas, and anterior lens displacement associated with aqueous
      misdirection glaucoma. Clinical signs and current therapeutic options are
      discussed for the general practitioner. A close working relationship with the
      regional veterinary ophthalmologist is advised.

PMID- 15948425
TI  - Feline glaucomas.
AB  - Cats are usually presented at a very late stage in the course of glaucoma when
      the eye is already blind. Secondary glaucoma because of another underlying ocular
      lesion is the most common form of glaucoma in the cat and is frequently
      associated with chronic anterior uveitis or intraocular neoplasia. Chronic stages
      of glaucoma in the cat are characterized by buphthalmus, anterior lens luxation,
      and exposure keratitis secondary to the enlarged globe. Ophthalmoscopic signs of
      glaucomatous retinal degeneration are only noticed in very advanced stages.
      Treatment of glaucoma in cats is usually aimed to keep the eye comfortable and
      within a normal intraocular pressure range. However, many antiglaucoma
      medications that are successfully used in humans and dogs are not very well
      tolerated by cats and, therefore, the selection of recommended drugs is limited
      in this species.

PMID- 15948426
TI  - Feline uveitis: diagnosis and treatment.
AB  - Uveitis is the inflammation of any or all parts of the vascular tunic of the eye;
      the vascular tunic includes the iris, the ciliary body, and choroid. A good
      knowledge base, up-to-date reference materials, and good instruments will improve
      the diagnosis of uveitis. Feline uveitis can be caused by numerous infectious
      agents in addition to neoplasia and less likely trauma. The infectious causes
      most commonly associated with feline uveitis include feline leukemia virus,
      feline immunodeficiency virus, feline infectious peritonitis, systemic fungal
      infections, toxoplasmosis, and bartonellosis. Neoplastic causes of uveitis can be
      primary or secondary. Iris melanoma is the most common primary uveal neoplasia
      and trauma-associated sarcoma is the second most common primary uveal neoplasia.
      Treatment for the clinical signs of anterior uveitis include topical steroidal or
      non-steroidal anti-inflammatory agents, parasympatholytic agents for ciliary
      spasm, to keep the pupil dilated, and to prevent posterior synechia. Posterior
      uveitis should be treated with systemic medications that will address the
      underlying cause. Enucleation of blind, painful eyes not responsive to
      medications is a means to alleviate the animal's discomfort and to further
      diagnose the underlying cause.

PMID- 15948427
TI  - Ocular manifestations of systemic disease in cats.
AB  - Systemic feline diseases (parasitic, bacterial, fungal, viral, neoplastic,
      metabolic, vascular, and immune-mediated) are often associated with ocular
      symptoms. An ocular examination is an important diagnostic tool and should be
      part of any physical examination. Conversely, cats afflicted with systemic
      disease require periodic ocular examinations for prognostic information and to
      prevent vision threatening complications. Typical feline systemic diseases
      encountered by the practicing clinician are presented with their commonly
      associated ocular signs.

PMID- 15948428
TI  - Feline chlamydiosis.
AB  - Chlamydiae are an important cause of acute and chronic conjunctivitis in cats.
      Until recently, only one organism was thought to infect cats, Chlamydophila felis
      (previously Chlamydia psittaci var. felis). Recently, other Chlamydia-like
      organisms belonging to the family Parachlamydiaceae, which comprises organisms
      that reside and proliferate within free-living amoeba, have been identified in
      cats with neutrophilic and eosinophilic conjunctivitis. The relative importance
      of these organisms and their amoebic hosts requires investigation. There is also
      weak evidence that chlamydiae may also be capable of causing reproductive tract
      disease and lameness in cats. Diagnosis of chlamydial conjunctivitis requires use
      of specialized culture techniques or the polymerase chain reaction. The
      antibiotic of choice to treat these infections is doxycycline; azithromycin is
      less effective. All cats in the household should be treated simultaneously. The
      zoonotic potential of these organisms appears low, but some precaution is
      warranted when handling affected cats.

PMID- 15948429
TI  - Feline ocular emergencies.
AB  - Feline ocular emergencies include any ophthalmic condition that has rapidly
      developed or is the result of trauma to the eye or periocular structures. Common
      feline emergencies include proptosis, lid lacerations, corneal ulcers, and
      foreign bodies. Complete ophthalmic examination including procurement of the
      minimal ophthalmic database (Schirmer tear test, fluorescein stain, and
      intraocular pressure measurement) should be obtained whenever possible to ensure
      that the complete and correct diagnosis is made. Concern for the patient's vision
      and ocular comfort should guide the practioner's diagnostic and therapeutic plan.
      This article reviews some of the more common feline ocular emergencies, including
      conditions affecting the orbit and globe, adnexa, conjunctiva, and cornea. Feline
      uveitis, glaucoma, and lenticular diseases are covered more thoroughly elsewhere
      in this issue.

PMID- 15948430
TI  - Communication skills.
AB  - Surveys of American Academy of Orthopaedic Surgeons members and patients indicate
      that orthopaedic surgeons are "high tech, low touch." According to patients and
      colleagues surveyed, orthopaedic surgeons are given high ratings by patients and
      colleagues for their skills in the operating room, but their listening and
      communication skills can be improved upon; they could listen better and show more
      empathy for their patients. Communication affects patient satisfaction, adherence
      to treatment, and physician satisfaction. Communication problems have also been
      cited as the most common factor in the initiation of malpractice suits. All
      orthopaedic surgeons can benefit from improving their communication skills.

PMID- 15948431
TI  - Complex regional pain syndrome.
AB  - Abnormal posttraumatic pain may delay recovery and severely impact health-related
      quality of life. The term complex regional pain syndrome describes abnormally
      intense and prolonged pain that is not related to tissue damage and is sometimes
      a sequela of injury. Various treatment strategies, including therapy, parental
      interventions, and peripheral surgery, are used to manage the condition.

PMID- 15948432
TI  - Acute pain following musculoskeletal injuries and orthopaedic surgery: mechanisms
      and management.
AB  - The undertreatment of acute pain associated with musculoskeletal conditions and
      surgical procedures is a focus of growing concern to orthopaedic surgeons.
      Fortunately, the armamentarium now includes recent advances in the understanding
      of how undertreated acute pain can lead to chronic pain, the development of new
      therapeutic agents, and new approaches to pain management. The concept of
      neuronal plasticity (the ability of neurons to profoundly alter their structure,
      function, or biochemical profile in response to repeated afferent sensory input)
      is now central to the understanding of the development of chronic pain from acute
      pain. Local inflammation in injured tissue increases the sensitization of
      specialized peripheral sensory neurons (nociceptors), leading to repeated
      afferent input into the central nervous system. Resolving inflammation before
      these events occur may prevent modifications in the central nervous system that
      lead to chronic pain. Therefore, it is important to reduce pain and inflammation
      at both the central and peripheral level. In addition to traditional agents
      (aspirin, nonspecific nonsteroidal anti-inflammatory drugs, opioids, local
      anesthetics, and regional blocks), more recently developed agents, such as
      cyclooxygenase-2 specific inhibitors, are now available. Combinations of these
      agents, as well as combinations of pharmacologic and nonpharmacologic approaches,
      are being used as multimodal therapy to treat the multiple sources of acute pain.
      Clinical practice guidelines for the management of acute pain now emphasize the
      incorporation of new knowledge into solid, evidence-based practice. This
      knowledge, combined with further understanding of the anatomic, physiologic,
      cellular, and molecular basis of pain, will provide the basis forfuture
      approaches to the management of acute pain in orthopaedic practice.

PMID- 15948433
TI  - A guide to reduce allogeneic transfusions in elective orthopaedic surgery.
AB  - The principles and techniques used to reduce or eliminate blood transfusions can
      be applied to the standard practice of orthopaedic surgery. The overall goal is
      to enable orthopaedic surgeons who are interested in reducing allogeneic
      transfusions to find a method that fits their practice.

PMID- 15948434
TI  - Blood management in orthopaedic surgery.
AB  - The need to provide the best possible care for patients, while balancing risk
      against benefit and respecting the patients' wishes, is the major reason to
      pursue blood management strategies. This is underscored by the decreasing supply
      of blood and its concomitant increasing cost. A philosophy of blood management is
      centered in the recognition of transfusion-associated risks and their avoidance
      through limited exposure to allogeneic blood and the use of appropriate
      alternatives.

PMID- 15948435
TI  - Blood management in total joint arthroplasty.
AB  - One of the primary goals in the perioperative care of orthopaedic patients
      undergoing surgery is the avoidance of allogeneic transfusion. There are a number
      of ways to lessen blood loss during surgical intervention including regional
      hypotensive anesthesia, careful and atraumatic surgical technique, and
      coagulation of bleeding surfaces. Achieving coagulation is difficult in spinal
      and arthroplasty procedures because of the large cancellous surfaces that are
      vascular and are not amenable to ligature or thermal coagulation. All measures of
      autologous blood salvage should be used including preoperative deposit of
      autologous blood, hemodilution techniques, intraoperative salvage (when
      appropriate), and postoperative retrieval and reinfusion. The use of
      perioperative recombinant erythropoietin is also a useful adjunct to promote
      stimulation of the bone marrow and increased red cell production. Although many
      infectious diseases that are transmitted through allogeneic blood transfusions
      have been lessened by better screening techniques, there is still potential life
      threatening reactions and viral transmissions that may be avoided by
      comprehensive blood management in joint arthroplasty.

PMID- 15948436
TI  - Decision making in contemporary shoulder arthroplasty.
AB  - Clinical experience with humeral implants has evolved over the past decade, along
      with a better understanding of shoulder anatomy and function. There is no
      question that surgeons are getting better at restoring normal anatomic
      relationships than in preceding decades. Whether or not this impacts implant
      longevity will only be known with time and further follow-up. Even over the short
      term, it is difficult to ascertain whether new prosthetic designs have improved
      patient function as well as has been implied by the related biomechanical
      studies. Most surgeons with experience using old and new systems realize a
      greater sense of predictability in achieving their surgical goals when using more
      modern implants. Concerns over the durability of prosthetic systems with multiple
      moving parts and hand-tightened locking mechanisms have almost been forgotten in
      shoulder arthroplasty, but time will also reveal their importance. New glenoid
      designs have been less exciting, the major problem being one of developing
      appropriate materials. Polyethylene does not behave like normal cartilage, and
      its wear is constant and unforgiving. Surgeons now better understand how to
      reconstruct the normal glenoid position and achieve more secure early fixation
      than in the past, but this does not promise long-term durability and freedom from
      complications.

PMID- 15948437
TI  - Arthroscopic treatment of anterior shoulder instability.
AB  - In the late 1980s and early 1990s, several advances in arthroscopic shoulder
      stabilization procedures were made. However, these early techniques were
      associated with higher failure rates compared with the traditional open
      procedures and therefore were not widely disseminated throughout the orthopaedic
      community. Because of improved understanding in anatomy and pathology in
      conjunction with dramatic technologic advances, the past decade has demonstrated
      significant improvement in the arthroscopic management of the unstable shoulder
      Evolution of arthroscopic techniques over the past 5 years to more closely
      resemble open procedures has led to clinical outcomes previously seen only with
      open procedures. Arthroscopy is becoming an attractive treatment option for an
      increasing number of orthopaedic surgeons.

PMID- 15948438
TI  - Current perspectives in the management of scaphoid nonunions.
AB  - When left untreated, scaphoid fractures follow a downward spiral resulting in
      carpal collapse and arthritis. The purpose of intervention is to allow a
      cartilage-wrapped bone to heal and maintain a smooth articular surface. Proposed
      treatment options for scaphoid nonunions have varied success rates. Using the
      Mack-Lichtman classification for nonunions, a plan can be formulated for
      individual patients based on motion loss, degenerative changes, carpal collapse,
      and fracture instability manifested by bone loss. Stable nonunions may benefit
      from bone grafting and internal fixation. Unstable nonunions require grafting and
      fixation. With the development of arthritis, grafting and fixation must be
      weighed against suitability of a proximal row carpectomy or a four-corner fusion
      with scaphoid excision. Advanced carpal collapse and arthritis mandates fusion,
      either limited or complete. CT allows preoperative planning to assess grafting
      requirements. MRI defines vascular supply fa vascular graft is considered.
      Vascularized graft options have multiplied as attention has been focused on the
      impact of improved blood supply on the avascular scaphoid. Patient- and fracture
      specific factors are important considerations when determining surgical options;
      underestimating their importance can compromise surgical results even with a high
      level of technical skill. Successful treatment of scaphoid nonunions remains a
      difficult challenge despite improvement in fixation devices and surgical options.
      By regarding injury status together with patient factors, surgical options can be
      narrowed and patient expectations managed more realistically.

PMID- 15948439
TI  - Ulnar-sided wrist pain: diagnosis and treatment.
AB  - Ulnar-sided wrist pain has often been equated with low back pain because of its
      insidious onset, vague and chronic nature, intermittent symptoms, and frustration
      that it induces in patients. Chronic ulnar-sided wrist pain may be accompanied by
      a history of workers' compensation claims and unrelenting and irresolvable pain,
      and it may occur in patients with dfficult personalities. Despite these issues,
      many patients with ulnar-sided wrist pain have pathologic lesions that may be
      amenable to surgical treatment.

PMID- 15948440
TI  - Soft-tissue balancing of the hip: the role of femoral offset restoration.
AB  - Inadequate soft-tissue balancing is a major yet often underemphasized cause of
      failure for primary and revision total hip arthroplasty. Accordingly,
      contemporary cemented and cementless hip prostheses have been designed with
      consideration of this issue, and this has substantially increased the long-term
      survival of total hip replacements. Therefore, it is important for orthopaedic
      surgeons to be familiar with the rationale, biomechanical principles, and
      clinical implications associated with soft-tissue balancing of the hip as well as
      strategies to avoid inadequate soft-tissue balancing and systematic techniques to
      restore adequate soft-tissue tensioning during total hip arthroplasty.

PMID- 15948441
TI  - Trochanteric osteotomies in revision total hip arthroplasty: contemporary
      techniques and results.
AB  - Revision total hip arthroplasty (THA) presents several challenges to the
      orthopaedic surgeon and typically requires the use of a more extensile surgical
      approach. Osteotomy of the greater trochanter can be considered as the ultimate
      extensile exposure in revision THA. The methods of trochanteric osteotomy can be
      categorized into three types: the standard trochanteric osteotomy, the
      trochanteric slide, and the extended trochanteric osteotomy. Although the
      standard osteotomy and trochanteric slide osteotomy provide excellent acetabular
      exposure, in the revision setting they are frequently associated with an
      unacceptably high rate of nonunion and proximal migration of the trochanteric
      fragment. The extended trochanteric osteotomy (ETO) has increased in popularity
      as the number and complexity of revision THAs continue to increase. Two commonly
      used techniques are the ETO via a posterolateral approach or via a modified
      direct lateral approach. Both techniques provide wide exposure of the acetabulum,
      facilitate femoral component exposure and removal, aid in canal preparation and
      femoral reconstruction, and allow for correction of proximal femoral deformity.
      The osteotomy fragment is easily secured and may be advanced distally to achieve
      proper tensioning of the abductors. Recent literature demonstrates that the ETO
      has a relatively low rate of nonunion and is associated with fewer intraoperative
      femoral fractures or cortical perforations, as well as decreased surgical time.

PMID- 15948442
TI  - Intertrochanteric femoral osteotomies for developmental and posttraumatic
      conditions.
AB  - Despite the numerous advances in technology and techniques for total hip
      arthroplasty, this surgery is often not the procedure of choice for all patients
      or for all hip conditions. Originally described as a treatment for femoral neck
      nonunions, the intertrochanteric femoral osteotomy retains an enduring role in
      the treatment of various posttraumatic and developmental hip conditions including
      femoral neck nonunions, iatrogenic or postsurgical deformities, leg-length
      inequality, osteonecrosis, slipped capital femoral epiphysis, deformities
      occurring after Legg-Calve-Perthes desease, and for certain patients with
      dysplasia and secondary arthritis. By correcting deformity (either acquired or
      developmental), the intertrochanteric osteotomy can restore a more normal
      biomechanical geometry to the hip joint, which can increase the likelihood of
      improved longevity of the articulation. Excellent results have been reported by
      numerous authors using this procedure alone or in association with simultaneous
      or staged osteotomy of the pelvis. Factors that are common to most successful
      series are an emphasis on proper patient selection, detailed preoperative step-by
      step planning, and meticulous intraoperative technique. Surgical intervention
      prior to the development of irreversible articular deterioration may result in
      dramatic short-term relief of pain because of improvements in biomechanics and
      relief of impingement. Long-term results include elimination of the need for
      total hip arthroplasty or postponement o f the need for this surgery for a
      meaningful number of years (such as 10 years or more).

PMID- 15948443
TI  - Alternative bearing surfaces: alumina ceramic bearings for total hip
      arthroplasty.
AB  - Osteolysis resulting from polyethylene wear debris is one of the most common
      causes of implant failure in young, active individuals who undergo total hip
      arthroplasty. Reducing wear may help extend the life of the implant in these
      patients. Contemporary alumina ceramic/alumina ceramic bearing articulations are
      harder, scratch resistant, and more hydrophilic than other bearing couples,
      resulting in reduced wear and reduction of particle load to the surrounding
      tissue. Therefore, bearings made of alumina ceramic may be a preferable bearing
      choice for younger, more active patients. To investigate this hypothesis, 495
      patients (514 hips), average age 53 years, were enrolled in a prospective,
      randomized, multicenter study comparing an alumina-on-alumina ceramic bearing to
      a cobalt-chromium-on-polyethylene bearing control. At an average of 4 years after
      implantation, no difference in clinical outcome was observed between groups.
      There were no fractures of the ceramic head or liner, nor were there any
      revisions caused by the ceramic liner. Another investigational group was added to
      the study 1 year after enrollment in the original study was closed. The same
      inclusion/exclusion criteria were used. A total of 194 consecutive patients (209
      hips) received an alumina liner that included a thin metal backing designed to
      allow bearing replacement and ease surgical assembly. At an averagefollow-up of
      30 months, no liner or head chips or fractures were observed in this group.

PMID- 15948444
TI  - Metal-on-metal: articulations for the new millennium.
AB  - Implants with metal-on-metal articulations (Metasul, Sulzer Medica, Winterthur,
      Switzerland [now Zimmer, Warsaw, IN]) have been used in nearly 300,000 total hip
      replacements. In three different clinical studies, clinical success has been
      demonstrated using this implant as measured by Harris hip scores, patient self
      assessment, and assessment of mechanical complications. Of a study group of 924
      patients who received this implant, the only reported complications were
      mechanical, incldding two cup loosenings (0.2%) and 36 dislocations (4.0%). In a
      randomized study, clinical resultsfor the group that received implants with metal
      on-metal articulation were comparable to those of the ceramic-on-polyethylene
      (control) group. Reports assessing retrieved implants with metal-on-metal
      articulation demonstrate low annual linear wear rates and no consequences of
      elevated cobalt ion levels at follow-up from 4 years to 26 years. In light of
      these data, the continued ise of metal-on-metal articulations is recommended for
      any patient who does not have compromised renal function.

PMID- 15948445
TI  - Conventional ultra-high molecular weight polyethylene: a gold standard of sorts.
AB  - Data from a series of four recent studies showed that conventional polyethylene
      liners sterilized by gamma irradiation in air and coupled with second-generation
      acetabular components outperformed first-generation components with consistent
      average wear behavior below 0.1 mm/yr. It was found that liners sterilized by
      gamma irradiation in air outperformed liners sterilized by gas plasma, indicating
      that cross-linking induced by gamma irradiation sterilization, even if the
      component is radiated in an oxygen environment, is essential for keeping wear
      rates low. No negative clinical effects were found on wear for conventional
      polyethylene sterilized by gamma irradiation in air with a shelf life up to 3
      years (r2 = 0.04, P = 0.60). Finally, 16-year temporal wear patterns for gamma
      irradiation in air sterilized components demonstrated no significant changes in
      wear rates over time, indicating that gamma irradiation sterilized liners with
      short shelf lives will not likely experience late increases in wear because of
      continued in vivo oxidation of the polyethylene. From these studies it was
      determined that standardized radiographic methods, optimal radiographs, serial
      measurements, and minimum 4-year follow-up are essential for reliable wear data.
      More specifically, it was concluded that a conventional ultra-high molecular
      weight polyethylene liner gamma irradiation sterilized in air with a shelf life
      less than 3 years, coupled with a second-generation cup, performs well in vivo
      and is unlikely to experience late increases in wear. Because no comparable in
      vivo data will be available for new cross-linked polyethylene materials for
      several years, conventional gamma irradiated polyethylene can be considered the
      industry's current gold standard for wear performance comparisons.

PMID- 15948446
TI  - Enhanced polyethylene implants: have we been there before?
AB  - Ultra-high molecular weight polyethylene (UHMWPE) has been used as a bearing
      surface in total hip arthroplasty for nearly 40 years. Early failures have been
      attributed to gamma irradiation in air sterilization, poor implant design, and
      high patient activity. Currently available implants address the problems of gamma
      irradiation in air by using sterilization methods that avoid oxidative
      degradation. Previous efforts to modify UHMWPE, including carbon reinforcement,
      hot isostatic pressure, and heat pressing, have not resulted in improved clinical
      performance. More recently, highly cross-linked UHMWPEs have been developed that
      markedly reduced wear in hip simulators. However, cross-linking also reduces the
      mechanical properties, including fatigue crack propagation resistance. Although
      early clinical results with highly cross-linked UHMWPE are favorable, longer
      follow-up will be necessary to determine whether the results of in vitro testing
      accurately reflect long-term in vivo behavior.

PMID- 15948447
TI  - Mobile-bearing knee systems: ultra-high molecular weight polyethylene wear and
      design issues.
AB  - In June 2004, the U.S. Food and Drug Administration Orthopaedic Advisory Panel
      recommended the reclassification of mobile-bearing knee systems for general use.
      This reflects the increasing use of mobile-bearing knee systems internationally,
      which is currently limited in the United States by regulatory requirement. Mobile
      bearing knee systems are distinguished from conventional, fixed-plateau systems
      in that they allow dual-surface articulation between an ultra-high molecular
      weight polyethylene insert and metallic femoral and tibial tray components. Their
      in vivo success is dependent on patient selection, design, and material choice,
      as well as surgical precision during implantation. Laboratory and clinical
      experience extending over 25 years with individual systems suggests that mobile
      bearing knee systems represent a viable treatment option for patients with knee
      arthrosis.

PMID- 15948448
TI  - Kinematics of mobile-bearing total knee arthroplasty.
AB  - In a comparison of in vivo knee kinematic patterns of mobile-bearing total knee
      arthroplasty with thosefrom studies of fixed-bearing total knee arthroplasty and
      the normal knee, no major differences in the "average" kinematic patterns of
      fixed- versus mobile-bearing implants was observed. However, there was less AP
      translation of both the medial and lateral femoral condyles during gait in
      patients with mobile-bearing implants. This is probably the result of the
      increased sagittal femorotibial conformity of most mobile-bearing implants, which
      reduces polyethylene shear stresses and should lessen polyethylene wear rates. In
      rotating-platform mobile-bearing implants, axial rotation occurs primarily on the
      inferior surface of the polyethylene bearing instead of on the superior surface,
      which reduces shear forces on the superior aspect of the polyethylene bearing,
      thereby lessening wear: Although the average axial rotational values after total
      knee arthroplasty were limited (< 10 degrees), a significant number of patients
      exhibited higher magnitudes of rotation (> 20 degrees), which exceeds the
      rotational limits of most fixed-bearing implants. Rotating-platform mobile
      bearing implants may therefore be advantageous in that they can accommodate a
      wider range of axial rotation without creating excessive polyethylene stresses.

PMID- 15948449
TI  - Unicompartmental mobile-bearing knee arthroplasty.
AB  - Two diferent mobile-bearing unicompartmental knee replacement designs have been
      available since the late 1970s. The primary difference between these two designs
      is that one has a constrained bearing in a track and the other has a freely
      moving bearing. Both implants are currently indicated for the treatment of
      patients with medial unicompartmental osteoarthritis and are available for use in
      the United States. The benefits of such designs are restoration of normal knee
      joint kinematics and protection of the polyethylene by reduction of high-contact
      stresses that occur with nonmobile-bearing designs. Experience has shown that
      careful patient selection and careful surgical technique both are factors
      critical to the success of mobile-bearing unicompartmental knee implants. The
      most important patient selection criteria have proved to be the diagnosis of
      anteromedial osteoarthritis with a passively correctable varus deformity and
      intact anterior cruciate ligament. Precise instrumentation is necessary to
      consistently balance and align a mobile-bearing implant. Ten-year survivorship
      data for freely mobile-bearing implants are available from multiple centers that
      show survivorship rates ranging from 85% to 98%, which are comparable to
      survivorship rates for total knee replacement.

PMID- 15948450
TI  - Mobile bearings in revision total knee arthroplasty.
AB  - Mobile-bearing hinged knee replacement systems were used early on for primary and
      revision knee arthroplasty, but they were associated with high failure rates.
      Third-generation modular rotating platform hinged knee replacement systems have
      evolved with modular diaphyseal engaging slotted and splined stems and
      metaphyseal filling and loading sleeves. Additionally, significant improvement of
      the articulation between the rotating hinge mechanism and tibial component with
      broad congruent surfaces has decreased the deleterious stresses that contributed
      to the failures of earlier designs. The excellent mid-term results of the S-ROM
      modular mobile-bearing hinge and modular rotating plaform nonlinked knee
      replacement systems provide solid evidence for expanding the indications for
      rotating platform revision systems.

PMID- 15948451
TI  - Clinical results and complications in mobile-bearing total knee arthroplasty.
AB  - The low-contact stress mobile-bearing implant has the longest continuous follow
      up, with over 25 years of data compiled in the designers' original study. In
      several peer-reviewed publications, the long-term outcome and clinical
      performance of the femorotibial articulation, patellar resurfacing, and various
      issues of surgical technique, such as cruciate retention or sacrifice, tibial
      axis alignment method of bone resection, cemented versus cementless implants, and
      the use of the lateral approach for patients with valgus deformed knees are
      analyzed. These results are compared with those of outcome studies of total knee
      arthroplasty in general. Results from a recent multicenter outcome study evaluate
      the survivorship results from surgeons around the world who have extensive
      experience with the low-contact stress implant.

PMID- 15948452
TI  - Extensor mechanism complications after total knee arthroplasty.
AB  - The patellofemoral joint is an important source of pain and complications
      following total knee arthroplasty. Anterior knee pain, patellar instability,
      fracture, rupture of the extensor mechanism, and a variety of miscellaneous
      problems affecting the patella can adversely affect the results of a total knee
      arthroplasty. Because patellofemoral complications after total knee arthroplasty
      often occur because of problems with patient selection, implant design, and
      surgical technique, it is important for orthopaedic surgeons treating patients
      with extensor mechanism complications after total knee arthroplasty to evaluate
      the entire knee replacement and base treatment on the etiology of the
      complication and not just the complication itself.

PMID- 15948453
TI  - Surgical treatment of the middle-aged patient with arthritic knees.
AB  - Arthritic knee disease is increasingly more common in the active aging
      population. The pathology seen in this patient group can run a spectrum of
      localized degenerative change through tricompartmental arthritis. Nonsurgical
      options to treat early symptoms are well known and often are effective. When
      nonsurgical management has failed, surgical intervention often is warranted.
      Arthroscopic debridement is considered in select patients with mechanical
      symptoms. Osteotomy continues to have a role in the treatment of young, active
      patients and may be particularly appropriate in combination with articular
      cartilage procedures. Unicompartmental and total knee arthroplasty are reliable
      treatments for patients with advanced stages of degenerative arthritis.

PMID- 15948454
TI  - Arthrodesis of the first metatarsophalangeal joint.
AB  - Arthrodesis of the first metatarsophalangeal joint is indicated in patients with
      symptomatic arthrodesis or advanced hallux valgus deformities that are
      unresponsive to nonsurgical treatment. Several fixation techniques have been
      described, including intefragmentary compression screws and/or dorsal plate
      fixation. Using these modern fixation techniques, the rate of fusion is between
      94% to 98%, with high patient satisfaction. Appropriate positioning of the fusion
      is important for satisfactory outcome.

PMID- 15948455
TI  - Correction of multiplanar hindfoot deformity with osteotomy, arthrodesis, and
      internal fixation.
AB  - Multiplanar deformity of the hindfoot is among the most daunting deformities of
      the foot and ankle to correct. Deformity correction must attempt to fix the
      overall orientation of the foot, and prior surgical procedures, arthritic
      conditions, neurologic abnormalities, musculotendinous insufficiency, and patient
      goals must be considered. The procedure must relieve pain, arthritis, or
      instability of the hindfoot and ankle, as well as pressure overload of the
      lateral foot, midfoot, and/or forefoot. The foot should achieve a plantigrade
      position that allows for easier shoe fitting and provide a stable plaform for
      weight bearing. When multiple deformities are present, a staged approach to
      surgical correction is needed. The goal is to create a plantigrade and stable
      hindfoot first, and then focus on the forefoot. Multiplanar and severe
      deformities require a variation of basic arthrodesis and osteotomy techniques.
      Properly placed wedge excisions and soft-tissue releases will enable a
      plantigrade correction. In some situations, even arthrodesis is insufficient to
      correct deformity, and residual hindfoot varus or valgus must be corrected with
      various types of osteotomy of the calcaneus. Osteotomies of the mid-tarsal region
      can be considered for residual pes cavus, forefoot supination, adduction, or
      abduction. An algorithmic approach is used in which the hindfoot is corrected
      first,followed by the midfoot and forefoot. Correction using multiplanar cuts and
      internal fixation to establish a plantigrade foot provides the best opportunity
      for a successful result.

PMID- 15948456
TI  - Nonsurgical management of low back pain and lumbar disk degeneration.
AB  - Lumbar disk degeneration is a ubiquitous and complex phenomenon. The etiology
      varies widely and may be dificult to identify. Many techniques have been proposed
      to manage the pain and disability resulting from disk degeneration. Medicines,
      bed rest, orthotics, physical therapy, chiropractics, selective injections, and
      intradiskal electrothermal therapy have been used. Some of these therapies have
      been more successful than others, but most have at least some role in the current
      techniques of helping patients deal with this syndrome. How best to use these
      tools in conjunction with patient education is critical to success.

PMID- 15948457
TI  - Spinal stenosis: pathophysiology, clinical and radiologic classification.
AB  - Stenosis is the narrowing of a hollow tube, in this case the central lumbar
      spinal canal, lateral recess, or foramen. Clinically, this narrowing produces
      neurovascular compression that may lead to pain. Lumbar spinal stenosis may be
      classified by etiology (for example, congenital or acquired) or by symptom
      complex (radiculopathy, neurogenic claudication, or mechanical back pain).
      Stenosis can also be classified radiographically, by the location of the stenosis
      (for example, central canal, lateral recess, or intervertebral foramen) or by the
      presence of deformity such as spondylolisthesis or scoliosis. Overlap occurs in
      these schemes of classification in that central stenosis with thecal sac
      compression typically leads to neurogenic claudication, whereas lateral recess
      compression is associated with compression of an individual nerve root and,
      therefore, radiculopathy. Because radiographic changes associated with stenosis
      are very common with aging, understanding the pathophysiology of lumbar spinal
      stenosis is critical in the assessment and management of related symptom
      complexes. Although symptoms may arise from narrowing of the spinal canal, not
      all patients with narrowing develop symptoms. The reason why some patients
      develop symptomatic stenosis and others do not is still unknown. Therefore, the
      term lumbar spinal stenosis refers not to the pathoanatomic finding of spinal
      canal narrowing, but rather to a clinical syndrome of lower extremity pain caused
      by mechanical compression on the neural elements or their blood supply.

PMID- 15948458
TI  - Nonsurgical and surgical management of lumbar spinal stenosis.
AB  - The symptoms associated with lumbar spinal stenosis can decrease quality of life
      and may cause patients to seek treatment. Except in rare cases of rapid
      neurologic progression or cauda equina syndrome, nonsurgical modalities should be
      the initial treatment choice. Activity modification, a variety of medications,
      epidural steroid injections, and other methods are recommended for pain
      reduction. A formal physical therapy program, which focuses on flexion-based
      exercises, may lead to improved patientfunction. Surgery is indicated in patients
      who remain symptomatic despite a course of nonsurgical therapy and who have
      advanced imaging studies that correspond to existing .symptoms. Adequate
      decompression of the neural elements and maintenance of bony stability are
      necessary for a good surgical outcome for patients with spinal stenosis.
      Laminectomy has long been the method of choice for thorough lumbar decompression.
      Preserving at least the lateral half of the facet joints bilaterally and bone in
      the area of the pars interarticularis minimizes the potential for iatrogenic
      instability. Numerous other decompression techniques have been described,
      including multilevel laminotomies, fenestration, distraction laminoplasty, and
      microscopic decompression. Arthrodesis, either with or without instrumentation,
      is also indicated in some patients. Several studies report that surgical
      treatment produces better outcomes than nonsurgical treatment in the short term;
      however, the results tend to deteriorate with time. Lumbar decompressive surgery
      can be complicated by epidural hematoma, deep venous thrombosis, dural tear,
      infection, nerve root injury, and recurrence of symptoms.

PMID- 15948459
TI  - Lumbar spinal stenosis: indications for arthrodesis and spinal instrumentation.
AB  - Surgical indications for simple decompression in patients with lumbar spinal
      stenosis are well established. Following these guidelines, surgeons can expect
      good and excellent outcomes in 75% to 90% of patients. Despite the publication of
      many studies pertaining to the addition of arthrodesis and instrumentation, the
      indications for adding these procedures to a decompression are much less clear.
      Preoperative and intraoperative factors must be carefully considered when
      contemplating the addition of arthrodesis in the setting of spinal stenosis. In
      patients with preoperative degenerative spondylolisthesis, scoliosis, or
      kyphosis, and those in whom stenosis develops at a previously decompressed
      segment, serious consideration should be givenfor inclusion of an arthrodesis.
      Fusion should also be considered for those patients with stenosis adjacent to a
      previously fused lumbar segment. Excision of a significant portion of the facet
      joints or radical excision of the intervertebral disk during the course of the
      decompression predispose the patient to postoperative instability. The addition
      of an arthrodesis will likely benefit these patients. Relative indications for
      the use of spinal instrumentation in the setting of spinal stenosis include
      correction of deformity, recurrent spinal stenosis with instability, degenerative
      spondylolisthesis, adjacent segment stenosis with instability, and multiple level
      fusions.

PMID- 15948460
TI  - Meniscus structure and function.
AB  - True appreciation of the structure and function of the knee joint meniscus is a
      relatively recent occurrence. Even decades after studies were published
      documenting the detrimental effects of meniscectomoy such as osteoarthritis, many
      physicians continued to advocate total meniscectomy for even minor meniscal
      pathology. Fortunately, the clinical approach to these problems has undergone
      dramatic change over the past 20 years. A review of the anatomy and
      ultrastructure of the meniscus, and its relationship to normal function in terms
      of load transmission, shock absorption, joint stability, lubrication, and
      nutrition will enable a better understanding of the rationale for meniscus
      preservation techniques, including meniscal repair and meniscal transplant.

PMID- 15948461
TI  - Inside-out meniscal repair.
AB  - Meniscal injuries are the most common surgically treated knee injury in the
      United States. Newer devices for an all-inside technique to repair the meniscus
      may have supplanted the arthroscopically assisted inside-out technique. The
      arthroscopically assisted inside-out technique is a well-established, highly
      successful method of repair. It is still necessary for certain types of meniscal
      repairs and some of its advantages cannot yet be matched by an all-arthroscopic
      method.

PMID- 15948462
TI  - All-inside meniscal repair.
AB  - All-inside meniscal repair has become a popular technique. The number of meniscal
      repairs done in the United States has increased dramatically since the
      introduction of the Meniscal Arrow (Linvatec Corp, Largo, FL). Although these
      devices are easy to use, there have been several compliations reported with their
      use. Newer devices (Mitek RapidLoc and Smith and Nephew Fas-T-Fix) allow
      tensioning of the construct after insertion. There are also problems and pitfalls
      with their use, but improvements continue to be made in all-inside meniscal
      repair devices.

PMID- 15948463
TI  - Meniscus transplantation: indications, techniques, clinical outcomes.
AB  - Although many meniscus tears can be successfully repaired, not all are
      salvageable, especially if considerable tissue damage has occurred. Meniscus
      transplantation has been shown to be an acceptable procedure for younger
      patients. The primary candidate is a patient younger than age 50 years who has
      had a total meniscectomy and who either has pain in the tibiofemoral compartment,
      arthroscopic evidence of articular cartilage deterioration, or both.
      Contraindications are advanced knee joint arthrosis with flattening of the
      femoral condyle, concavity of the tibial plateau, and osteophytes that prevent
      anatomic seating of the meniscus allograft; axial malalignment; knee joint
      instability; knee arthrofibrosis; muscular atrophy; and prior joint infection.
      Prophylactic meniscus transplantation after total meniscectomy is not recommended
      in asymptomatic patients who do not demonstrate articular cartilage deterioration
      because long-term predictable success rates are not available. Most clinical
      studies on meniscus transplantation have reported improvements in knee function
      and pain, especially in patients who have symptoms affecting daily activities, as
      there are few if any other available treatment options.

PMID- 15948464
TI  - Indications for prosthetic replacement in proximal humeral fractures.
AB  - Prosthetic replacement is a good treatment option in osteoporotic patients with
      four-part fractures, fracture-dislocations, head-split fractures with more than
      40% articular surface involvement, anatomic neck fractures, dislocations present
      for longer than 6 months, and selected three-part fractures. Early prosthetic
      replacement of proximal humeral fractures has a better outcome than late
      reconstructive prosthetic management. Prosthetic design features specific
      forfracture care have led to a reduction in complications. Techniques will
      continue to improve as prosthetic design features specific for fractures evolve.

PMID- 15948465
TI  - Outcome after treatment of proximal humeral fractures with humeral head
      replacement.
AB  - After its initial description by Neer and associates, humeral head replacement
      has been widely used to treat complex fractures of the proximal humerus. Many
      studies have confirmed that the treatment of proximal humeral fractures with
      humeral head replacement is associated with reliable pain relief as well as good
      patient satisfaction. A limited number of studies have also suggested that the
      prostheses have reasonable longevity, with the rate of prosthesis survival at 83%
      to 94% at 10 years. The functional outcome after the procedure, however, has not
      been as predictable. Using various outcomes scoring instruments, multiple studies
      have reported a wide range of results. Some authors have reported mostly
      disappointing outcomes, whereas others have reported generally satisfactory
      results. The most critical factor influencing the long-term outcome appears to be
      the position of the greater tuberosity. Other factors that are also associated
      with a good outcome include younger age, minimal delay between the traumatic
      event and the surgical procedure, and the absence of any neurologic deficit. For
      young patients with a complex proximal humeral fracture, humeral head replacement
      still remains a viable treatment option. However, whenever possible, most authors
      favor open reduction and internal fixation because of the issues affecting the
      longevity of the prosthesis. By understanding and minimizing the risk factors
      leading to a poor result, a reasonable functional outcome, reliable pain relief
      and a high rate of patient satisfaction can be expected after treatment of
      proximal humeral fractures with humeral head replacement.

PMID- 15948466
TI  - Complications of humeral head replacement for proximal humeral fractures.
AB  - Humeral head replacement has been widely used for the treatment of complex
      proximal humeral fractures. The procedure is associated with a high rate of
      patient satisfaction as well as reliable relief of pain. The functional outcomes,
      however, have been variable. Reported complications include infection, neurologic
      injury, intraoperative fracture, instability, tuberosity malunion and nonunion,
      rotator cuff tear, heterotopic ossification, glenoid erosion, and stiffness. When
      technical factors such as tuberosity malunion or component malpositioning are
      considered as postoperative complications, the incidence of complications is
      relatively high. This high rate of complications, in turn, may be related to the
      wide range of reported functional outcomes.

PMID- 15948467
TI  - Classification and initial management of patients with unstable pelvic ring
      injuries.
AB  - Unstable pelvic ring injuries in hemodynamically unstable patients are life
      threatening emergencies that many orthopaedic surgeons encounter in practice.
      Therefore, it is important to be up to date regarding current methods of
      evaluating, assessing, and treating patients with these complex and severe
      injuries. Surgeons should first determine whether patients have hemodynamic
      instability and identify the source of the hemorrhage. Patients should then be
      assessed for stabilization of unstable pelvic ring injuries.

PMID- 15948468
TI  - Surgical management of pelvic ring injuries.
AB  - Posterior pelvic ring injuries disrupt the weight-bearing function of the pelvis
      and cause deformity that results in pain and loss of function. The indications
      for reduction and fixation are the presence of instability and/or deformity.
      Surgical fixation of the pelvic ring is divided into anterior and posterior ring
      injuries. In many instances, reduction and fixation of the anterior pelvic ring
      is not needed after reduction and fixation of the posterior pelvic ring. Although
      techniques exist for both open and closed reductions, the main dfficulty remains
      achieving anatomic restoration of the pelvis. Whether posterior pelvic ring
      injuries are best treated using closed reduction and fixation or open reduction
      and fixation remains a controversial topic.

PMID- 15948469
TI  - Expected outcomes after pelvic ring injury.
AB  - Pelvic ring injuries are a result of high-energy trauma and are often associated
      with nonskeletal injuries. Although malunions and nonunions are rare with the use
      of current techniques of reduction and fixation, outcome studies show that these
      injuries have long-lasting effects. Associated urologic and neurologic injuries
      are commonly the determinants of outcome.

PMID- 15948470
TI  - Reducing complications in the surgical treatment of intertrochanteric fractures.
AB  - The increasing number of hip fractures in the elderly constitutes a health care
      burden. The subset of unstable intertrochanteric hip fractures is important
      because the treatment of these fractures continues to be hampered by a moderate
      complication rate. Osteoporosis, fracture geometry, and the success of surgical
      treatment are strong predictors of outcome. The surgeon is in control of fracture
      reduction, implant selection, and implant placement, all of which must be
      optimized to ensure the success of surgical intervention.

PMID- 15948471
TI  - Femoral neck fractures.
AB  - Despite the tremendous advances in the science and practice of orthopaedic
      surgery, anesthesia, and perioperative care, repair of displaced fractures of the
      neck of the femur is still associated with complications in up to one third of
      patients. The risk of nonunion and osteonecrosis in particular is virtually the
      same today as in the 1930s. Recent data from well-designed outcome studies now
      indicate that the most predictable, durable, and cost-effective procedure for an
      active elderly patient with a displaced femoral neck fracture is total joint
      arthroplasty; however, not all patients are candidates for this procedure, and
      the potential complications of arthroplasty, including mortality, may be more
      difficult to manage and more severe than those associated with internal fixation.
      The laudable goal of obtaining fracture healing and maintenance of a viable
      femoral head can be successfully achieved in a number of patients.

PMID- 15948472
TI  - Damage control orthopaedics: evolving concepts in the treatment of patients who
      have sustained orthopaedic trauma.
AB  - In some groups of polytrauma patients, particularly those with chest injuries,
      head injuries, and those with mangled extremities, early total care of major bone
      fractures may be potentially harmful. Delaying all orthopaedic surgery, however,
      is also not always the best approach. In these situations, damage control
      orthopaedics, which emphasizes the stabilization and control of the injury rather
      than repair will add little additional physiologic insult to the patient and is a
      treatment option that should be considered.

PMID- 15948473
TI  - The biology of alternative bearing surfaces in total joint arthroplasty.
AB  - Periprosthetic osteolysis is currently the dominant limiting factor in joint
      arthroplasty longevity. Because this process is predominantly a biologic response
      to particulate wear debris and/or corrosion products, alternative bearing
      surfaces and highly cross-linked polyethylenes have been developed in an attempt
      to reduce the incidence of wear-induced periprosthetic osteolysis. These
      alternative bearing surfaces currently include ceramic-on-polyethylene, ceramic
      on-ceramic, metal-on-metal, and metal or ceramic on highly cross-linked
      polyethylene. Although these alternative bearings diminish the generation of
      polyethylene debris, metallic or ceramic debris is produced. In addition, the
      biologic response to debris generated from alternate bearings is not fully
      elucidated and is related not only to particle number, but also to particle size,
      shape, composition, and surface area.

PMID- 15948474
TI  - Beyond bone grafting: techniques in the surgical management of benign bone
      tumors.
AB  - The traditional surgical treatment of benign bone tumors has been curettage and
      autologous bone graft or marginal resection of expendable bones. These procedures
      are associated with good results in most patients and should be considered the
      standard against which newer treatments are compared. Recently, however, surgeons
      have been evaluating the results of treatments using limited surgical approaches,
      including percutaneous treatments, alternatives to autograft bone, and thermal or
      cytotoxic adjuvant therapies. The goal has been to improve patient outcomes by
      decreasing perioperative morbidity and enhancing surgical efficiency. This
      process has been facilitated by the availability of multiple bone grafting
      materials and substitutes, the use of cross-sectional imaging, and technology
      such as that used with radiofrequency ablation. Techniques using these therapies
      in two benign bone tumor models are described. The use of percutaneous
      radiofrequency ablation, now used for both benign and malignant disease, is
      reviewed as a surgical alternative for osteoid osteoma. The role of adjuvant
      therapies such as liquid nitrogen and phenol, as well as the indications for
      resection, are described in the management of giant cell tumors of bone.

PMID- 15948475
TI  - Bone graft alternatives in the treatment of benign bone tumors.
AB  - Most bone grafting procedures are done during spinal fusion and to treat patients
      with skeletal trauma. Very few studies have addressed the bone grafting of
      skeletal defects after benign bone tumor excision. Contained defects have been
      treated with autogenous bone grafts, fresh-frozen allografts, freeze-dried
      allografts, demineralized bone matrix, and ceramic materials. Additionally, bone
      morphogenetic proteins may provide a future treatment option for bone tumor
      reconstruction.

PMID- 15948476
TI  - Musculoskeletal infections in children: basic treatment principles and recent
      advancements.
AB  - Pediatric musculoskeletal infections are common disorders that can result in
      significant disability. Because the understanding, diagnosis, and treatment of
      infections of the bones, joints, and soft tissues have continued to improve over
      time, it is important for orthopaedic surgeons to have an understanding of the
      etiology, diagnosis, basic treatment principles, and recent advancements to
      achieve successful outcomes. Although each infectious process is unique, there
      are certain treatment principles that apply to all pediatric musculoskeletal
      infections. These include prevention, a prompt and accurate diagnosis, and timely
      medical and/or surgical intervention. Continued evaluations are mandatory to
      assure good long-term outcomes. Because the effects of infection may last beyond
      the acute episode in pediatric patients, long-term follow-up is needed to assess
      for late sequelae such as angular deformities and limb-length inequalities.

PMID- 15948477
TI  - Adolescent idiopathic scoliosis: etiology, anatomy, natural history, and bracing.
AB  - Adolescent idiopathic scoliosis is a three-dimensional deformity of the spine.
      Despite active efforts by different research teams, the etiology of scoliosis
      remains unclear. Treatment of scoliosis requires a solid understanding of the
      natural history of the disorder as well as sound clinical judgment. The
      evaluation, monitoring, and institution of conservative treatment such as bracing
      can present a challenge to the orthopaedic surgeon. Clinical monitoring is the
      only intervention necessary in most patients. A detailed review of the patient's
      history as well as a careful physical examination can help establish the
      diagnosis and the risk for progression. Skeletal maturity, gender; growth
      velocity, curve location, and magnitude are factors that can help assess the
      likelihood of progression. Bracing is the only nonsurgical measure proven to have
      any effect on halting the progression of scoliosis. Other forms of conservative
      treatment have not been shown to significantly modify the natural history of
      idiopathic scoliosis. Bracing results are directly related to compliance with
      brace treatment; therefore, optimal results cannot be achieved without the
      patient's cooperation and family support.

PMID- 15948478
TI  - Lenke classification system of adolescent idiopathic scoliosis: treatment
      recommendations.
AB  - The Lenke and associates classification system of adolescent idiopathic scoliosis
      (AIS) was developed to provide a comprehensive and reliable means to categorize
      all surgical AIS curves. This classification system requires analysis of the
      upright coronal and sagittal radiographs along with the supine side bending
      radiographic views. The triad classification system consists of a curve type (1
      6), a lumbar spine modifier (A, B, C), and a sagittal thoracic modifier (-, N,
      +). All three regions of the radiographic coronal and sagittal planes, the
      proximal thoracic, main thoracic, and thoracolumbar/lumbar are designated as
      either the major curve (largest Cobb measurement) or minor curves with the minor
      curves separated into structural and nonstructural types. The recommendations are
      that the major and structural minor curves are included in the instrumentation
      and fusion and the nonstructural minor curves are excluded. Overall, the
      classification system is treatment directed; however, there are other aspects of
      the radiographic and clinical deformity that may suggest deviation from the
      recommendations of the classification system. The ultimate goal of this
      classification system is to allow organization of similar curve patterns to
      provide comparisons of various treatment methods to provide optimal treatment for
      each AIS surgical patient.

PMID- 15948479
TI  - The use of outcomes instruments in the assessment of patients with idiopathic
      scoliosis.
AB  - Outcomes research is becoming an increasingly vital aspect of modern medicine.
      With current cost containment measures, the need for effective and reproducible
      treatment options is essential. The methodology associated with these outcomes
      studies is varied. Studies involving radiographic assessment can be effective
      with respect to instrumentation performance. However, studies that use physical
      parameters for outcomes do not include the patient's perception of outcome. For
      surgical outcome to be considered successful, patient satisfaction must be taken
      into account. The tools and methods used to assess patient satisfaction are
      complicated, as these outcomes measures must stratify the various aspects of
      daily living, personal perception, and overall well-being. The interpretation and
      analysis of these patient-perceived data can prove challenging because the
      variability within a group can be large based on human factors. Nonetheless,
      patient satisfaction should be of prime importance and should be addressed in any
      outcome study. An overview of the parameters and terms associated with outcomes
      research in the assessment of patients with scoliosis is important in order to
      improve existing care or aid in the evaluation of new standards of care.

PMID- 15948480
TI  - The use of video-assisted thoracoscopic surgery in the treatment of adolescent
      idiopathic scoliosis.
AB  - The video-assisted thoracoscopic approach has become a useful adjunct in the
      treatment of scoliosis. This minimally invasive anterior approach allows access
      to the thoracic spine, providing a means of achieving disk excision and anterior
      body fusion. The advantage of this technique is the limited chest wall dissection
      required to reach the anterior thoracic spine. More recently, techniques have
      been developed to allow anterior instrumentation for an entirely endoscopic
      method of performing scoliosis correction. This approach is appropriate for
      curves less than 70 degrees when only the thoracic curve is structural. The
      outcomes of this approach are promising and suggest reduced morbidity compared
      with open anterior approaches.

PMID- 15948481
TI  - Indications and techniques for anterior-only and combined anterior and posterior
      approaches for thoracic and lumbar spine deformities.
AB  - Over the past several years, anterior treatment of spinal pathologies has gained
      popularity. Currently, there is much debate about the relative advantages of the
      thoracoscopic approach versus open thoracotomy, and laparoscopic over open lumbar
      surgery. Also, there is evolving information regarding patient morbidity after
      anterior treatment for spinal pathologies. Clearly, the anterior, middle, and
      posterior columns of the spine must be assessed before treatment is initiated.
      For one- or two-level pathologies, often the anterior column can be accessed in
      the thoracic spine through the pedicles, facetjoints, transverse processes, and
      ribs on one side (costotransversectomy). Similarly, in the lumbar spine the disks
      can be approached as either a posterior lumbar interbody fusion or a
      transforaminal lumbar interbody fusion procedure. For multilevel pathologies,
      usually a separate anterior approach is recommended. There are many factors to
      consider in determining whether to use anterior-only or combined anterior and
      posterior techniques in the pediatric and adult population. Anterior-only
      treatment is more likely to apply to a younger, healthier patient with normal
      bone stock and limited pathology. Patients with large deformities, borderline
      bone stock, and multisegmental pathologies are more likely to benefit from
      combined treatment.

PMID- 15948482
TI  - Anterior surgery in the thoracic and lumbar spine: endoscopic techniques in
      children.
AB  - Therapeutic modalities for disorders of the pediatric spine must include video
      assisted thoracoscopy. The endoscopic approach to the spine has involved an
      evolutionary approach. What began as an isolated drainage of a vertebral abscess
      has continued as a method of single diskectomy, release of the anulus fibrosus
      with or without ligation of segmental vessels, rib resection for costoplasty, rib
      harvesting for intervertebral fusion and, most recently, insertion of
      correctional implants with or without spinal fusion. Video-assisted thoracoscopic
      surgery offers the potential to decrease surgical morbidity associated with
      traditional open procedures. The ability of video-assisted thoracoscopic surgery
      to achieve spinal release and the results of early outcomes and cost are
      comparable to those of open thoracotomy. The improvement in video technology with
      multichip cameras has significantly improved and enhanced the ability to identify
      structures in the chest through small incisions (portals). This technology allows
      spine surgeons to perform surgical intervention comparable to thoracotomy.
      Instead of using a 9- to 12-inch incision, four to five portals of approximately
      2 cm are used; thus, the cosmetic efects of the scoliosis surgery are enhanced.
      The potential benefits of this procedure include diminished postoperative pain,
      decreased length of hospitalization, increased wound care, and early return to
      prehospital activities.

PMID- 15948483
TI  - Three questions for the next generation.

PMID- 15948485
TI  - Selected to lead.

PMID- 15948484
TI  - Moral courage.

PMID- 15948486
TI  - Is dentistry a business or a profession?

PMID- 15948487
TI  - 2004 ACD Awards. William John Gies Award.

PMID- 15948488
TI  - Fourteen characteristics of effective leaders in dentistry.
AB  - Leadership can be learned, especially through careful observation of effective
      leaders. Fourteen characteristics of effective leaders in the dental office and
      in organized dentistry are discussed. These include: positive mental attitude,
      faith, goals in life, organization, time management, interdependency and synergy,
      consistency, communication, self-renewal, empathy and humility, creativity,
      personal responsibility and drive, ability to say no, and charisma.

PMID- 15948489
TI  - The challenge of leadership in technology and education.
AB  - The leadership qualities necessary today in technology, education, and other
      modern organizations include the ability to recognize rapid changes in
      organizational environments and ensure continuous transformation and adaptability
      to that change. The important skills of such leaders include understanding their
      own business, articulating vision, creating a positive culture, communicating
      effectively, and measuring results. Rapidly emerging technology is prone to
      misunderstanding by those who mistake the surface features of how technology
      works with the functional opportunities it provides. Organizations that transform
      processes in parallel by adopting new technologies can expect much larger
      productivity gains than can those who merely insert technology. The problems of
      memory, speed, and cost have been addressed; the new challenge of technology is
      making it universal. Education in America is in danger. The infrastructure is
      outdated and it is not oriented toward change. Jobs will follow competence.
      Although the challenges of leadership today, especially in technology and
      education, are great, so is the opportunity for impact and the excitement of
      bringing diverse skills to bear.

PMID- 15948490
TI  - Is there anything left for the next generation of leaders?
AB  - Dean Arthur A. Dugoni is celebrated as the "dean of deans" or American dental
      schools. His service as a practitioner, rich network of relationships,
      recognition of emerging opportunities, respectful treatment of all, and ability
      to make people care and promote loyalty are identified. Significant issues remain
      for future leadership to address: dental caries is on the rebound, insurance is
      inadequate to provide needed coverage, prevention must be strengthened, education
      struggles with too few teachers and high tuition, the mobility of dentists is
      unrealistically restricted, and the pool of retired dentists who want to donate
      their services is hobbled by regulations. The ADA can take the leadership in some
      of these areas, but there is much left to be done by the next generation of
      individual leaders in the mold of Dean Dugoni.

PMID- 15948491
TI  - Leadership as a passionate expression.
AB  - The essence of leadership is passion, and there are many forms of exemplary
      leadership, just as there are many causes in which we can invest our passions.
      The chair of the board of regents of the University of the Pacific describes her
      passion for the mission of the university, which includes "preparing
      students...for responsible leadership in their careers and communities." She also
      describes the passionate leadership of the dental school dean, Arthur A. Dugoni,
      and of three graduates of the school.

PMID- 15948492
TI  - Leadership in research: organizing genius.
AB  - Science has become complex. Its success is increasingly becoming a matter of
      collaboration based on established infrastructures and professional norms in
      response to environmental challenges. Leadership in such situations means
      organizing the genius inherent in great groups. Three examples--the Manhattan
      Project, mapping the human genome, and rapidly understanding the nature of the
      SARS virus--are analyzed, showing a trend away from the individual scientist to a
      model based on simultaneous competition and collaboration.

PMID- 15948493
TI  - Leadership: a new look, a new time, and established leadership.
AB  - The executive director of the American Dental Association characterizes
      leadership as involving inspiration, vision, and hope in the service of change.
      The need is great and the opportunities of numerous. Leadership has been built at
      the ADA through identifying a shared set of core values and through a billion
      dollar national Campaign for Dental Education. Although the future of the
      profession is bright, the outstanding leadership challenges include: increasing
      access, the cost and faculty shortages in dental education, globalization,
      emerging biotechnology, licensure, increasing the public's perceived value of
      oral health, and workforce matters.

PMID- 15948494
TI  - Leadership: creating a cuiture of caring.
AB  - Leadership is characterized in terms of accomplishing mutual goals for the
      organization, its employees, and its community through vision and creating a
      community of caring. The examples of Herb Kelleher of Southwest Airlines, Walt
      Disney, and Dean Arthur A. Dugoni of the University of the Pacific are used to
      illustrate how this style of leadership plays out in specific accomplishments.

PMID- 15948495
TI  - Audacious leadership.
AB  - Three leaders in dentistry are presented as case studies. G.V. Black played a
      leading role in moving dentistry from a trade to a profession. William J. Gies
      helped lay the scientific foundation for dentistry. Arthur A. Dugoni has
      emphasized the human dimension of the profession and built relationships among
      key constituencies. What these audacious leaders share in common is an expansive
      vision of dentistry that transcended the confusions of the times and the energy
      and personal skills to enlist the cooperation of diverse groups in achieving
      these larger views.

PMID- 15948496
TI  - White coat principles.
AB  - The White Coat Ceremony, which many dental schools use to mark the transition to
      patient care, is an opportunity to reflect on the values of dental practice.
      Eight principles are offered for consideration: 1 ) patient care is the point of
      practice; 2) the doctor-patient relationship is essential; 3) discuss options and
      possibilities; 4) mistakes will be made; 5) tell the truth; be assertive; 7 )
      consult; and 8) manage your stress and your life.

PMID- 15948497
TI  - The professions.
AB  - The professions have been described in terms of their prestige and income,
      specialized skills and knowledge, protected markets, control over entry and
      discipline of members, common identity and values, long careers, managed
      relationships with nonprofessionals, licensure, ethics, and service to clients
      and the public. As useful as these characteristics are, they fail to capture the
      essence of the professions, especially the classic ones such as medicine and
      dentistry. A five-part definition is proposed, consisting of a community
      (including patient, professional, and peers), treating individuals in a
      customized private and personal fashion based on diagnosis, in a trusting
      relationship where the professional acts as an agent rather than engaging in
      economic exchanges. The evolution of the medical profession is discussed as an
      illustration of the way professions evolve and to reveal some of the historically
      "taken-for-granted" aspects of professionalism. The fact professional knowledge
      is both public and scientific and personal and unsusceptible to objective
      reduction is a paradox. The continued viability of professions such as dentistry
      depends on protecting against threats to the five essential characteristics that
      define professionalism.

PMID- 15948498
TI  - Looking toward future challenges.

PMID- 15948499
TI  - Advocating health care on Capitol Hill.

PMID- 15948500
TI  - New AMS CEO is no stranger. Veteran society staffer David Wroten assumes role of
      EVP.

PMID- 15948501
TI  - Informed consent lacking?

PMID- 15948502
TI  - Ray Biondo, MD.

PMID- 15948503
TI  - Intensive participation accelerates clinical improvement. AFMC consultation
      achieves high satisfaction scores.

PMID- 15948504
TI  - Primary cardiac paraganglioma.
AB  - A primary cardiac paraganglioma was identified in a 59-year-old Caucasian male
      who complained of palpitations and chest pain. The neoplasm (4.7 cm in diameter)
      was surgically excised from the left posterior atrium. Adriamycin-based adjuvant
      chemotherapy was administered. The patient returned to his normal activities.
      There is no evidence of recurrence or metastasis after two years and nine months.

PMID- 15948505
TI  - The Arkansas Southern Rural Access Program: strategies for improving health care
      in rural areas of the state.
AB  - Rural residents often have poorer health than their urban counterparts. Many
      factors, including the availability of rural health care providers, contribute to
      their poorer health status. The Arkansas Southern Rural Access Program offers
      innovative strategies for improving health care in rural areas of the state
      including assisting with recruitment and retention, developing rural health
      networks, nurturing rural health leaders, and facilitating the availability of
      development capital to enhance the rural health care infrastructure. This paper
      describes the program, its components and successes, as well as how these
      resources can be accessed by health care providers around the state.

PMID- 15948506
TI  - Scripting for all team members.
AB  - Dental team training will only become more important as the profession becomes
      increasingly complex and dependent on technology. With the expansion of dental
      services, software, and technologies, dental teams have much more to deal with
      than ever before. Only by applying clear scripting to your dental business
      systems will your team truly excel.

PMID- 15948507
TI  - Restoring the interproximal zone using the proximal adaptation technique--Part 2.
AB  - In this era of modern adhesive dentistry, clinicians are still faced with
      challenges from microleakage, recurrent decay, and sensitivity. Many of the
      challenges are a result of using yesterday's restorative techniques and
      principles with the new formulations of biomaterials. Procedures such as the
      proximal adaptation and the oblique layering techniques offer modifications to
      the nonadhesive principles discussed in Part I (The Compendium, December 2004),
      while providing the patient and clinician with the 3 primary objectives of
      restorative dentistry: prevention, preservation, and conservation. Using
      stratification techniques and thorough adhesive protocol as illustrated in this
      article allows clinicians to provide restorations that have improved physical
      characteristics while reducing the effects of polymerization shrinkage. Other
      benefits of these adhesive procedures include enhanced chromatic integration,
      ideal anatomical form and function, optimal proximal contact, improved marginal
      integrity, and longer lasting directly placed composite restorations.

PMID- 15948508
TI  - All-ceramic systems: case presentation and discussion.

PMID- 15948509
TI  - Bioactive glass and bioabsorbable membrane in the treatment of a maxillary class
      II furcation defect: case report with 6-month re-entry.
AB  - The combination of bone graft materials with guided tissue regenerative
      procedures has been shown to have predictable positive results in periodontal
      defects, especially furcations. The following case report will demonstrate a
      severe class II furcation defect in a maxillary molar that was treated with
      combination therapy using bioactive glass and a bioabsorbable membrane made of a
      copolymer of polylactic/polyglycolic acid. Six-month re-entry revealed
      substantial clinical fill of the furcation defect. Comparison radiographs also
      demonstrated fill in the region.

PMID- 15948510
TI  - Tissue engineering: what does it mean? Why is it important?

PMID- 15948511
TI  - What is apical patency and does it matter?

PMID- 15948512
TI  - The keys to successful associateships.
AB  - When a practice is running at a high volume and stress is increasing, dentists
      often feel that it might be time to add an associate. This can be a good decision
      if the practice has the right data-driven systems in place. Conversely, if the
      scheduling system is inefficient and not managed properly, adding an associate
      will only increase the practice stress levels. Once the right systems are in
      place, hiring an associate still requires excellent communication and training
      skills on the part of the dentist.

PMID- 15948513
TI  - Changing periodontal concepts: treatment considerations.
AB  - Many clinical trials conducted during the last decade have clarified
      controversial issues and resulted in changed periodontal paradigms. These
      modified concepts have therapeutic implications. Some salient altered periodontal
      concepts include the following: The mere presence of pathogens will not initiate
      periodontal diseases. Most subgingival bacteria reside in biofilms. Periodontal
      diseases are infections. Periodontal pathogens can be transferred between family
      members. The host response can be protective and destructive. Gingivitis does not
      usually proceed to periodontitis. Risk factors in conjunction with bacteria and
      the host response can affect the severity of disease, patterns of destruction,
      and the response to therapy. Many medical conditions (eg, diabetes, smoking, and
      HIV infection) may predispose patients to periodontitis. Associations between
      periodontitis and a number of systemic ailments (eg, diabetes, adverse pregnancy
      outcomes, and cardiovascular disease) have been detected and are being
      investigated to determine if there is a cause-and-effect relationship. Diagnostic
      and therapeutic implications of these altered paradigms are addressed throughout
      the article.

PMID- 15948514
TI  - Artistic placement of a micro matrix direct composite for the restoration of a
      single maxillary central incisor.

PMID- 15948515
TI  - Immediate definitive CAD/CAM restoration of a non-submerged implant.
AB  - Implant placement has become a widely accepted treatment for tooth replacement.
      There are many restorative options, but it is best for the patient and most
      efficient for the office if the implant is placed and restored in as few
      appointments as possible. If diagnosis is thorough and accurate, placing the
      implant and doing a definitive restoration in 1 appointment can be as predictable
      as the traditional 2 appointment technique. Restoring the implant with computer
      assisted designed and machined porcelain can provide predictable fit, esthetics,
      and restoration and be clinically efficient.

PMID- 15948516
TI  - The role of power scalers in periodontics.

PMID- 15948517
TI  - The Universal Prep.

PMID- 15948519
TI  - Adhesive dentistry: where are we today?

PMID- 15948518
TI  - Comparison of two over-the-counter tooth whitening products using a novel system.
AB  - Tooth whitening is one of the most widely accepted esthetic procedures in
      dentistry. Various treatment options include in-office and prescribed at-home
      bleaching procedures, over-the-counter bleaching kits, and whitening dentifrices.
      This study evaluated and compared a 6% hydrogen peroxide tooth bleaching gel
      delivered on polyethylene film (HP) with an 18% carbamide peroxide brush-applied
      liquid gel (CP). A total of 59 subjects completed this 2-week, examiner blind,
      randomized, parallel group study. Both treatments were applied twice daily for 2
      weeks according to the manufacturer's instructions. Evaluations for oral safety
      and Vita tooth shade were conducted by a dental examiner at baseline and 2 weeks
      after product use. In addition, the ShadeVision System was used to determine
      changes in Vita shade and L*a*b* values. Based on both the examiner and
      ShadeVision System assessments, both treatments significantly improved tooth
      shade. Improvements in Vita tooth shade based on the adjusted mean for HP were
      2.64 (P < 0.001) and 2.33 (P < 0.001) for the examiner and ShadeVision System
      assessments, respectively, compared with improvements of 1.04 (P = .004) and 0.42
      (P = 0.029) for CP users, respectively. The difference between treatments was
      found to be significant for both the examiner (P = .005) and ShadeVision (P =
      .001) assessments. Findings from the L*a*b* data derived from the ShadeVision
      System were in agreement with Vita assessments, with significant differences for
      changes in L*, a*, and b* in favor of HP users (P = .001). In this study, the
      ShadeVision method of color analysis was relatively easy to use and demonstrated
      significant differences between 2 OTC whitening products using both Vitapan and
      L*a*b* means of assessment.

PMID- 15948520
TI  - It's great to be at the YMCA.

PMID- 15948521
TI  - Merck VIOXX "warning" is questioned.

PMID- 15948522
TI  - Ultimate failure.

PMID- 15948523
TI  - A difference of opinion.

PMID- 15948524
TI  - Standing united.

PMID- 15948525
TI  - Paying for the best.

PMID- 15948526
TI  - A preemptive strike.

PMID- 15948527
TI  - Poisoning hospitalizations among Texas adolescents: age and gender differences in
      intentional and unintentional injury.
AB  - Using 1999 Hospital Discharge Data, this study examines age and gender
      differences in the pattern of poisoning hospitalizations of Texas youngsters (N =
      1246) aged 10 through 17 years and investigates self-inflicted poisoning as a
      function of age and gender. Nearly three quarters of poisoning admissions are
      girls and two thirds of admissions are older children (aged 15 through 17 years).
      Analgesics and psychotropic drugs are the two most common agents used. Nearly 1
      in 3 admissions among younger children aged 10 through 14 years and 1 in 2 among
      older children are due to analgesics, with a higher proportion of female
      admissions. One quarter of admissions among both age groups are due to
      psychotropic drugs, with nearly equal proportions of boys and girls. Intentional
      poisoning admissions are significantly higher among girls in both age groups.
      Older children are 1 1/2 times more likely than younger children, and girls are 2
      times more likely than boys to be at risk for self-inflicted poisoning
      admissions. Fifty-three percent of female and 39% of male self-inflicted
      poisoning admissions are due to analgesics. Psychotropic drugs caused 29% of male
      and 21% of female self-inflicted admissions. Accidental and intentional poisoning
      is a public health concern requiring intervention. Residents in family practice
      and pediatrics need increased training to become proactive in educating
      adolescents and their parents about the dangers of drug overdosing.

PMID- 15948528
TI  - Nurses force Schwarzenegger retreat.

PMID- 15948529
TI  - Arnold imitates art.

PMID- 15948530
TI  - Arbitrator: hospital must tie admissions to RN staffing.

PMID- 15948531
TI  - Jury still out on health minister Dosanjh.

PMID- 15948532
TI  - Pyramid schemes.

PMID- 15948533
TI  - Social ills.

PMID- 15948534
TI  - Forces of magnetism.

PMID- 15948535
TI  - National estimates of cancer patients survival in Italy: a model-based method.
AB  - AIMS AND BACKGROUND: To provide model-based estimates of all cancers patient
      survival in Italy and in Italian large geographical areas (North-West, North
      East, Center, South), where only partial coverage of cancer registries data is
      available, and to describe them in terms of time trends. Moreover, to measure the
      degree of representativeness of cancer patient survival obtained from Italian
      cancer registries data. METHODS: Relative survival in the four main Italian
      geographical areas was estimated by a parametric mixture model belonging to the
      class of "cure" survival models. Data used are from Italian cancer registries,
      stratified by sex, period of diagnosis and age. The Italian national survival was
      obtained as a weighted average of these area-specific estimates, with weights
      proportional to the number of estimated incident cases in every area. The model
      takes into account also differences in survival temporal trends between the
      areas. RESULTS: Relative survival for all cancers combined in Italian patients
      diagnosed in 1990-1994 was estimated to be higher in women (53%) than in men
      (38%) at 5 years from the diagnosis. The survival trend is increasing by period
      and decreasing by age, both for men and women. The greatest gain in terms of
      survival was obtained by the elderly, with annual mean growth rates in the period
      1978-1994 equal to 3.5% and 3.2% for men and women, respectively. More than 50%
      of the youngest cancer patients were "cured", whereas for the elderly this
      proportion dropped to 15% and 25% for men and women, respectively. The South of
      Italy had the lowest survival and the North the most pronounced increase.
      CONCLUSIONS: The obtained national survival estimates are similar, but not
      identical, to previously published estimates, in which Italian registries' data
      were pooled without any adjustment for geographical representativeness. The four
      Italian areas have different survival levels and trends, showing variability
      within the country. The differences in survival between men and women may be
      explained by the different proportion of lethal cancers. Among males, most cases
      had a poor prognosis (lung and stomach cancers), whereas among females the
      largest proportion was made up of curable and less lethal cancers (breast
      cancer).

PMID- 15948536
TI  - Study of sunbathing in children: the preliminary evaluation of a prevention
      program.
AB  - AIMS AND BACKGROUND: Sunburn during childhood is associated with an increased
      risk for developing melanoma in an adult age. The aim of the present study was to
      define the validity of our educational program in order to teach the positive
      effects and risks of sun exposure during childhood. PATIENTS AND METHODS: We
      conducted a population-based, case-control study in primary schools of three
      towns in Northern Italy (Brescia, Bergamo and Trento) between 2001 and 2002. The
      study was carried out on 1945 pupils (aged 8-9 years) and included 1309 case
      children who received an educational program before the summer to increase
      awareness towards sun exposure and 636 control children who did not. Parents of
      case and control children were interviewed using a questionnaire about their
      children's skin characteristics, sun protective behavior and sunburns. The
      questionnaire was completed twice, before and after the summer, to verify the
      changes of sun exposure habits. RESULTS: A significant decrease in sunburns was
      demonstrated in the group of subjects who received the educational program,
      indicating the validity of our operative procedure (from 14.6% to 10%, P = 4 x
      10(-4). CONCLUSIONS: Our educational melanoma program may be important to
      disseminate in a wider range of children a correct education on sun exposure
      during childhood.

PMID- 15948537
TI  - Hepatic artery administration of docetaxel in liver metastases from breast
      carcinoma: a feasibility study.
AB  - AIMS AND BACKGROUND: Taxanes are largely metabolized and almost exclusively
      excreted in the feces by the liver through the biliary pathway, thus providing a
      rationale for investigating the activity of their hepatic artery delivery in case
      of liver metastases. STUDY DESIGN: The aim of this study was to assess the
      feasibility of administering docetaxel via the hepatic artery in advanced breast
      cancer patients in whom the liver was the only or the predominant site of
      metastatic involvement. The dose was increased cycle by cycle in a prospective
      manner. RESULTS: Ten eligible patients were enrolled. The median administered
      dose in the last cycle was 65 mg/m2 (range, 40-100 mg/m2). The treatment was
      generally well tolerated, and only one patient stopped after two cycles because
      of toxicity. Four of the 9 eligible patients with assessable liver tumors
      achieved an objective response. After a median follow-up of 41 months, 4 of the
      10 eligible (and 11 treated) patients were alive with a median overall survival
      of 46 months. CONCLUSIONS: The administration of docetaxel via the hepatic artery
      is feasible. The highly interesting response and survival results observed in
      this limited series of patients warrant further studies.

PMID- 15948538
TI  - Impact of concurrent radiotherapy on chemotherapy total dose and dose intensity
      in patients with early breast cancer.
AB  - AIMS AND BACKGROUND: A retrospective analysis was conducted to evaluate the
      tolerability as well as the impact of concurrent adjuvant CMF chemotherapy and
      radiation therapy on total CMF dose and dose intensity. METHODS: The medical
      records of 59 patients who had received conservative or radical surgery for
      breast cancer were analyzed. All patients had been assigned to 6 cycles of "1,8
      CMF" adjuvant chemotherapy and concomitant radiation therapy. Total drug dose and
      dose intensity were calculated. Toxicity was recorded scored according to WHO
      criteria. RESULTS: A total of 355 cycles was administered. Fifty of 59 patients
      received at least 85% of the programmed chemotherapy total dose, the median value
      being 100% (range, 42-100). The median relative dose intensity was 0.97 (range,
      0.42-1.01). Forty-four of 59 (75%) patients experienced grade 3-4 neutropenia (20
      febrile neutropenia) and 29 (49%) required G-CSF support. CONCLUSIONS: This
      retrospective analysis showed that it is possible to give concurrent CMF and
      breast radiation while ensuring adequate chemotherapy total doses and dose
      intensities to most patients. However, G-CSF support is required in a significant
      proportion of patients.

PMID- 15948539
TI  - Cisplatin and weekly docetaxel as first-line therapy in patients with advanced
      non-small cell lung cancer a phase II study.
AB  - BACKGROUND: Based on the results of previous phase I studies, in the current
      phase II trial we evaluated the efficacy and toxicity of cisplatin plus weekly
      docetaxel in the treatment of advanced non-small cell lung cancer (NSCLC).
      PATIENTS AND METHODS: The eligibility criteria for the study included newly
      diagnosed stage IIIB/IV NSCLC, age < or = 75 years, Eastern Cooperative Oncology
      Group performance status of 0-2, adequate organ functions, and signed informed
      consent. The chemotherapy regimen consisted of cisplatin, 80 mg/m2 on day 1, and
      docetaxel, 25 mg/m2 on days 1, 8 and 15 every 4 weeks. RESULTS: Between January
      2002 and December 2003, 31 patients with NSCLC were enrolled in the study. An
      objective response rate of 40% (95% CI, 21-60) was obtained in 27 assessable
      patients. The median time to progression was 6.4 months (range, 2.5-26.3) and
      median overall survival was 10.01 months (range, 5-28.3). The regimen was well
      tolerated with no grade 4 toxicity. CONCLUSIONS: Cisplatin plus weekly docetaxel
      is an effective and well-tolerated regimen in chemo-naive patients with advanced
      NSCLC. A phase III study of weekly versus the conventional regimen of every three
      weeks should be conducted to compare the survival benefits, toxicity profile and
      quality of life.

PMID- 15948540
TI  - A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin
      induced peripheral neuropathy.
AB  - AIMS AND BACKGROUND: In addition to bone marrow suppression and renal toxicity,
      neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic
      agents like taxanes, cisplatin and vinca alkaloids. Neurotoxicity can cause
      antitumor therapy discontinuation or dose regimen modification. The aim of the
      present exploratory study was to investigate the activity of acetyl-L-carnitine
      in reversing peripheral neuropathy in patients with chemotherapy-induced
      peripheral neuropathy. METHODS AND STUDY DESIGN: Twenty-seven patients (16 males
      and 11 females) with paclitaxel and/or cisplatin-induced neuropathy (according to
      WHO recommendations for the grading of acute and subacute toxic effects) were
      enrolled. Patients received at least one cisplatin- (n = 5) or one paclitaxel- (n
      = 11) based regimen, or a combination of both (n = 11). Patients with
      chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1
      g/die i.v. infusion over 1-2 h for at least 10 days. RESULTS: Twenty-six patients
      were evaluated for response having completed at least 10 days of acetyl-L
      carnitine therapy (median, 14 days; range, 10-20). At least one WHO grade
      improvement in the peripheral neuropathy severity was shown in 73% of the
      patients. A case of insomnia related to ALC treatment was reported in one
      patient. Acetyl-L-carnitine seems to be an effective and well-tolerated agent for
      the treatment of chemotherapy-induced peripheral neuropathy. CONCLUSIONS: Our
      preliminary results should be confirmed in double-blind, placebo controlled
      studies.

PMID- 15948541
TI  - Treatment of uterine sarcoma at the University of Florence from 1980-2001.
AB  - PURPOSE: To correlate the treatment used in uterine sarcoma with outcome. The
      prognostic importance of pathology, clinical parameters and treatment are
      analyzed. PATIENTS AND METHODS: Forty patients (median age, 59 years; range, 37
      85) with histologically verified uterine sarcoma were identified from a database
      compiled at the University of Florence from 1980 to 2001. Patients were followed
      for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had
      leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had
      endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in
      22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified
      grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively. RESULTS: At the
      time of analysis, 58% of patients had died and 42% were alive, with a median
      survival of 2 years from the initial diagnosis. Cause-specific survival for the
      entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our
      series, univariate analysis for cause-specific survival did not demonstrate
      statistical significance for histology, grade, stage or age. There appeared to be
      a significant impact for postoperative radiotherapy in reducing local recurrence
      with a total dose higher than 50 Gy. CONCLUSIONS: Our data favor treatment for
      uterine sarcoma with radical surgery plus irradiation, even in elderly patients.

PMID- 15948542
TI  - Long-term results in patients affected by testicular seminoma treated with
      radiotherapy: risk of second malignancies.
AB  - AIMS: To report clinical results in patients with testicular seminoma treated
      with postoperative radiotherapy with regard to survival, acute and late toxicity,
      and risk of second malignancy. MATERIALS AND METHODS: 176 stage I-Il testicular
      seminoma patients treated with radiotherapy from 1964 to 1994 at the Radiotherapy
      Division of Pisa University, using 60Co or Linac, were analyzed retrospectively.
      The follow-up ranged from 0.13 to 32.37 years, with a median of 12.1 years. The
      observed numbers of second malignancies were compared with those expected, taking
      into account age, sex, and incidence rates from the Tuscany Tumor Registry.
      RESULTS: Overall and specific survival at 10-15 years were 89-82% and 93-92%,
      respectively. Multivariate analysis revealed a significantly better survival in
      patients younger than 50 years and in those treated with Linac. Severe late
      sequelae occurred in 8% of the patients. Sixteen second malignancies were
      observed (14 solid tumors and 2 leukemias); median latency was 13 years (range, 3
      27) and the observed/expected ratio 1.4 (P not significant). Solid cancers were
      localized in the bladder (2), kidney (2), skin (2), stomach (1), prostate (1),
      lung (1), larynx (1), uvea (1) and contralateral testicle (1); 1 patient
      presented an intestinal carcinoid and 1 a metastasis from an unknown primary. The
      risk of a second malignancy was higher in the patient group receiving less than
      4000 cGy (observed/expected, 2.8; P = 0.015). CONCLUSIONS: The study confirmed
      the high cure rate in stage I-II seminomas after postoperative radiotherapy.
      Incidence of a second malignancy was higher than expected, but the difference was
      not statistically significant.

PMID- 15948543
TI  - External beam radiotherapy in the treatment of male breast carcinoma: patterns of
      failure in a single institute experience.
AB  - AIMS AND BACKGROUND: We analyzed our own results in the treatment of male breast
      cancer patients with respect to local control, overall survival and possible
      prognostic factors for local and distant control. METHODS: Thirty-one patients
      with 32 carcinomas of the male breast were treated with radiotherapy. Twenty-five
      patients received radiotherapy to the chest wall including or not regional
      lymphatics after initial mastectomy (n = 23) or after surgery for local
      recurrence (n = 2). Median total dose was 60 Gy to the chest wall and 46 Gy to
      regional lymphatics. Seven patients with metastatic disease were referred for
      palliative radiotherapy. RESULTS: Overall survival after postoperative
      radiotherapy was 40% after a median follow-up of 4.3 years. Actuarial 3-, 5- and
      10-year survival was 82.6%, 56.5% and 43.5%, respectively. Five-year progression
      free survival was 62.5%. Survival was significantly affected by the presence of
      lymph node metastases (P <0.001). Local recurrence was seen in one patient after
      29 months. CONCLUSIONS: Postoperative radiotherapy is important in the management
      of male breast cancer to improve local control and progression-free survival,
      resulting in one local failure in our analysis. The presence of lymph node
      metastases significantly impairs survival.

PMID- 15948544
TI  - Italian survey in postoperative radiation therapy for prostate carcinoma by the
      AIRO National Working Group on Prostate Radiotherapy: definitive results.
AB  - AIMS AND BACKGROUND: The National Working Group on Prostate Radiotherapy of AIRO
      (Associazione Italiana Radioterapia Oncologica, Italian Association of
      Radiotherapeutic Oncology) was established in March 2001. A retrospective multi
      center survey was performed to analyze the patterns of care for prostate cancer
      patients treated with postoperative radiotherapy following radical prostatectomy
      in Italy with regard to the year 2000. MATERIALS AND METHODS: A structured
      questionnaire was mailed to 47 Italian radiotherapy centers to assess patient
      accrual in the postoperative setting in the interval comprised between period
      January-December 2000. Numbers of patients treated for different stages, specific
      prognostic factors indicating the need for adjuvant radiotherapy, fractionation
      schedules and prescription doses were acquired as well as other clinically
      important factors such as radiotherapy timing and the use of hormone therapy.
      More technical features of the treatment, such as patient positioning, mode of
      simulation, typical field setup and dose prescription criteria were also included
      in the questionnaire. RESULTS: The questionnaire was returned by 24 radiotherapy
      Institutions (51%) with a total number of 470 patients treated postoperatively in
      the year 2000. An average of about 20 patients were enrolled by each radiotherapy
      center. The age range was 45-81 years. Radiotherapy was delivered within 6 months
      of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157
      (34.6%), the treatment was delivered as a salvage approach for biochemical or
      micro-macroscopic recurrence. Most of patients had locally advanced stage disease
      (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins,
      capsular invasion, Gleason pattern score > 7 were present in about 50% of
      patients. CONCLUSIONS: The study confirmed that important risk factors for
      recurrences are present in a significant percentage of patients treated by
      radical prostatectomy. The number of patients that would benefit from adjuvant
      radiotherapy is therefore potentially very large. Future prospective studies
      should be conducted to assess and to clarify the respective roles of adjuvant and
      salvage radiotherapy in prostate cancer patients.

PMID- 15948545
TI  - Results of whole brain radiation therapy in patients with brain metastases from
      colorectal carcinoma.
AB  - AIMS AND BACKGROUND: Carcinoma of the colon-rectum is an infrequent cause of
      brain metastases, constituting 1.5% of all metastatic lesions to the brain. We
      reviewed our experience in the treatment of brain metastases from colorectal
      cancer to define the efficacy of whole brain radiation therapy as a palliative
      measure in this setting of patients. METHODS: Twenty-three consecutive cases of
      brain metastasis from colorectal cancer treated between 1999 and 2004 were
      identified in the files of the Division of Radiotherapy of the A Businco Regional
      Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor
      characteristics and categorized according to the RTOG RPA classes. RESULTS:
      Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed
      extracranial metastases. Fourteen patients were classified as RTOG RPA class II
      and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions
      in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic
      improvement was observed. The median follow-up and survival time for all the
      patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of
      death was the brain metastasis. CONCLUSIONS: Despite the disappointing survival
      time, external radiation therapy to the whole brain proved to be an efficacious
      palliative treatment for patients with multiple or inoperable brain metastasis
      from colorectal cancer.

PMID- 15948546
TI  - What is the optimal number of lymph nodes to be dissected in colorectal cancer
      surgery?
AB  - BACKGROUND: Regional lymph node (LN) involvement in colorectal cancer (CRC)
      identifies the stage and the subset of patients who would benefit from adjuvant
      chemotherapy. We performed a retrospective analysis to determine if the number of
      recovered LNs was associated with long-term outcome in patients operated on for
      stage II and III CRC. PATIENTS AND METHODS: Hospital records of 179 patients with
      CRC followed in our unit from 1997 to April 2003 were reviewed. RESULTS: On
      average 11.68 +/- 7.3 LNs were sampled per surgical specimen. Sampling of at
      least nine LNs appeared to be the minimum number required for accurately
      predicting LN involvement (P = 0.002). Three-year rates of disease-free survival
      (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower
      in patients with fewer than nine LNs sampled (P = 0.032, P = 0.006 and P = 0.04,
      respectively). However, this had no impact on the three-year distant metastasis
      free survival rate (DMFS) (P = 0.472). In stage II disease, patients with nine or
      more LNs dissected had significantly higher three year DFS and LRFS rates than
      the subgroup with fewer than nine LNs dissected (P = 0.024 and P = 0.015,
      respectively), but this did not have any effect on DMFS or OS (P = 0.406 and P =
      0.353, respectively). CONCLUSION: Current protocols provide adjuvant treatment in
      stage III patients; the problem is to correctly determine stage by recovering as
      many LNs as possible.

PMID- 15948547
TI  - Intraoperative gamma probe detection of head and neck paragangliomas with 111In
      pentetreotide: a pilot study.
AB  - AIMS AND BACKGROUND: The aim of this study was to assess whether intraoperative
      radiolocalization of head and neck paragangliomas with 111In-pentetreotide may
      increase surgical effectiveness, reducing the risk of recurrence. METHODS: Our
      study included eight patients with untreated, recently diagnosed paragangliomas
      (four unilateral and four bilateral tumors of the carotid body). After i.v.
      injection of approximation 150 MBq 111In-pentetreotide, preoperative somatostatin
      receptor scintigraphy (SRS) was performed. SPECT of the neck was performed at
      four hours and planar images of the head and neck were also obtained at four and
      24 hours post injection. Scintigraphy was always compared with the results of
      conventional imaging methods (MRI, angiography and sonography). Intraoperative
      detection was performed on 11 lesions 24 hours after radiopharmaceutical
      administration using a handheld gamma probe. RESULTS: Preoperative SRS showed
      high radiotracer uptake in all patients. All the intraoperatively detected
      lesions were radically resected and histologically confirmed to be involved by
      tumor. No false positive results were recorded. Gamma probe detection revealed a
      small intracranial extension not detected by other imaging methods in a patient
      with a paraganglioma of the right carotid, and partial involvement of the carotid
      artery in another patient. During follow-up (median 3.5 years; range, 4 months-7
      years) all patients remained disease free according to all parameters.
      CONCLUSIONS: To our knowledge, this is the first experience of radioguided
      surgery in paraganglioma. Although our study included a relatively small number
      of patients, we suggest that intraoperative gamma probe detection may be a
      powerful tool to improve surgical effectiveness.

PMID- 15948548
TI  - Analysis of metastatic involvement of interpectoral (Rotter's) lymph nodes
      related to tumor location, size, grade and hormone receptor status in breast
      cancer.
AB  - AIMS AND BACKGROUND: This study was aimed at analyzing metastatic involvement in
      interpectoral (Rotter's) lymph nodes in relation to tumor location, size, grade
      and hormone receptor status in primary breast cancer. METHODS: The study included
      172 female patients undergoing surgery for breast cancer at the University
      Hospital for Tumors, Zagreb, Croatia from November 2001 to August 2003. In
      addition to the standard surgical procedure, interpectoral (Rotter's) lymph nodes
      were removed in all of the patients. Serum levels of the tumor marker CA 15-3
      were determined before surgery and hormone receptor status after surgery.
      RESULTS: Rotter's lymph nodes were identified in 67% of the patients, with
      metastatic involvement being found in 20% of the Rotter's nodes. Metastatic
      involvement of Rotter's nodes in patients with negative and positive axillary
      lymph nodes was 4% and 35%, respectively. When we looked at the location of the
      tumor in patients with metastatic involvement of Rotter's nodes, we found that
      tumors located in the upper quadrants were more prone to metastasis to Rotter's
      nodes; there was a significant positive correlation between tumor location and
      positive Rotter's nodes (r = 0.953, P = 0.012). As regards tumor size, Rotter's
      nodes were identified in 15%, 20% and 30% of stage T1 (< 2 cm), T2 (2-5 cm) and
      T3 (> 5 cm) tumors, respectively. Hormone receptor status showed no statistically
      significant difference in the expression of estrogen and progesterone receptors
      between patients with and those without positive Rotter's nodes. Of 35 Rotter's
      node-positive patients, 31.4% had elevated serum levels of CA 15-3; the level was
      significantly higher in Rotter's-positive patients compared to those with
      negative (or absent) Rotter's nodes. CONCLUSIONS: The results show that one-fifth
      of breast cancer patients, or even one-third of those with positive axillary
      lymph nodes, are discharged with positive interpectoral lymph nodes that remain
      undiagnosed. As the nodes can be surgically removed without additional
      mutilation, exploration of Rotter's lymph nodes should be introduced into routine
      clinical practice.

PMID- 15948549
TI  - Prognostic factors in early glottic carcinoma implications for treatment.
AB  - AIM: In this study we aimed to determine the prognostic factors affecting local
      control (LC) in limited glottic carcinoma treated with definitive radiotherapy
      (RT). MATERIAL AND METHODS: Between June 1991 and December 2001, 114 patients
      with early squamous-cell carcinoma of the glottis were treated with definitive RT
      at our institution. Only four (3.5%) patients were women. The median age was 60
      (27-79). Fifteen percent, 72% and 13% of the patients had Tis, T1 and T2 tumors,
      respectively. Forty-three (37.7%) patients had anterior commissure invasion.
      Prior to RT 35 (31%) patients had undergone vocal cord stripping and two (2%)
      cordectomy. A median dose of 66 Gy (50-70.2) was given over a median period of 46
      days (20-60). Univariate and multivariate analyses were performed for LC. The
      prognostic parameters analyzed for LC were T classification, anterior commissure
      involvement, total RT dose, and overall treatment time. RESULTS: Five-year local
      and regional control rates were 84.2% and 97.7%. RTOG grade 3-4 late side effects
      were observed only in one (0.9%) patient. In 15 patients with local failure,
      salvage treatment consisted of partial laryngectomy in eight patients and total
      laryngectomy in five. One of the remaining two patients was medically inoperable,
      and the other refused salvage surgery. In one of the three patients with regional
      failure, salvage surgery was applied and the other two were given palliative
      chemotherapy because of unresectable disease. Following salvage treatments, the
      ultimate five-year LC rate was 96.9% and the five-year larynx preservation rate
      was 91.1%. Second primary cancer was diagnosed in 17 (14.9%) patients. Only one
      patient developed distant metastases and two patients died of laryngeal cancer.
      While T2 disease and anterior commissure involvement were found to be unfavorable
      prognostic factors significantly influencing LC in univariate analyses, only T2
      disease remained independent in multivariate analysis. CONCLUSION: In patients
      with early glottic carcinoma, T classification proved to be the only independent
      prognostic factor affecting LC after primary radiotherapy according to the
      results of this study.

PMID- 15948550
TI  - Human papillomavirus detection by hybrid capture II and residual or recurrent
      high-grade squamous cervical intraepithelial neoplasia after large loop excision
      of the transformation zone (LLETZ).
AB  - AIMS AND BACKGROUND: The purpose of this study was to assess the association
      between highly-oncogenic types HPV DNA detection by Hybrid Capture II (HCII) and
      residual or recurrent high-grade cervical intraepithelial neoplasia (CIN 2 or 3)
      during the follow-up of women submitted to large loop excision of the
      transformation zone (LLETZ). STUDY DESIGN: In this cohort study, 94 women
      submitted to LLETZ because of CIN 2 or 3 between March 2001 and September 2002
      were followed up twice yearly until September 2003. Follow-up visits consisted of
      an interview regarding clinical, social and demographic characteristics
      complemented with gynecological examination with specimen collection for Pap test
      and HCII and colposcopy. Eighty-one patients attended the first visit (mean 4.8
      months, range 3-6) and 75 the second visit (mean 10.9 months, range 7-17 months).
      McNemar's test to assess the variation of HPV DNA detection following LLETZ, odds
      ratios (OR) to evaluate the correlation between HPV DNA positivity and
      residual/recurrent CIN during follow-up, and logistic regression to assess the
      risk of residual/recurrent CIN were used. RESULTS: There was a strong and
      significant reduction in HPV detection after LLETZ (P < 0.001). HPV DNA detection
      was correlated with residual/recurrent CIN at the first (OR = 103.4; 95% CI 5.5
      to 1961.2) and second (OR = 12.7; 95% CI 1.1 to 345.5) follow-up visits.
      Multivariate analysis showed HPV persistence as a stand-alone risk factor for
      residual/recurrent CIN (OR = 50.3; 95% CI 3.8 to 663.1). CONCLUSIONS: High risk
      HPV DNA detection decreased substantially after CIN treatment with LLETZ, but HPV
      persistence was strongly correlated with residual/recurrent CIN.

PMID- 15948552
TI  - Ifosfamide encephalopathy: a case report.
AB  - The aim of this short communication is to discuss the mechanism, modality and
      treatment of ifosfamide encephalopathy. We present the case of a 52-year-old
      woman treated with this alkylating agent who developed severe neurotoxicity. It
      was resolved with administration of Methylene blue, abundant intravenous
      hydration and interruption of ifosfamide.

PMID- 15948551
TI  - Localized hand-foot syndrome after intra-arterial hepatic chemotherapy with
      floxuridine: a clinical case.
AB  - Hand-foot syndrome is a toxic effect of some chemotherapy agents such as 5
      fluorouracil (5-FU), capecitabine and liposomal doxorubicin. The symptoms and
      signs are localized erythema and paresthesia. Floxuridine (FUDR) is an analogue
      of 5-FU, used for arterial hepatic infusion in patients affected by liver
      metastases from colorectal cancer. A patient who was treated for colorectal
      cancer with liver metastases underwent locoregional chemotherapy with FUDR and
      systemic chemotherapy with FOLFOX4. After three cycles he developed severe
      painful dermatitis of the right leg. Abdominal X-ray showed displacement of the
      catheter to the right common iliac artery. Treatment was discontinued and the
      patient had a rapid recovery.

PMID- 15948553
TI  - Primary malignant melanoma of the stomach.
AB  - We report a 54-year-old patient with a complaint of weakness, abdominal pain and
      weight loss. During the clinical examination a palpable tumor resistance in the
      abdomen was found as well as iron deficiency anemia. Gastroscopy showed an
      exulcerated, dark brown, fungiform tumor about 4 cm in diameter at the great
      curve of stomach. Endoscopic biopsy revealed the diagnosis of malignant melanoma
      by demonstrating the presence of melanin containing tumor cells in gastric
      mucosa. The patient underwent subtotal gastrectomy, appendectomy and splenectomy.
      The diagnosis of gastric melanoma with regional lymph node metastases, as well as
      metastases in appendix adjacent tissue was confirmed by histology and
      immunohistochemistry. In three years follow up period patient developed cerebral
      and retroauricular subcutaneous metastases that were treated by surgery, adjuvant
      chemotherapy and radiotherapy. Finally, an explorative laparatomy was revealed
      advanced intraabdominal tumor dissemination with dark pigmented ascites.
      Concerning that all available diagnostic procedures failed to prove other site of
      melanoma, presented case was considered as primary gastric melanoma as a possible
      rare site of tumor.

PMID- 15948554
TI  - Giant mixed retroperitoneal sarcoma with metaplastic bone and cartilage
      formation: radiological-pathological correlation.

PMID- 15948555
TI  - Metastatic tumors of the umbilicus: report of two cases and review of the
      literature.
AB  - An umbilical nodule may be an early or late sign of metastatic spread from an
      internal malignancy. Usually it appears when the internal malignancy is widely
      disseminated and has been previously diagnosed. More rarely, such a nodule is the
      first sign of disease and eventually results in the diagnosis of the primary
      tumor. We present two cases which document examples of both events, in order to
      focus on the most relevant aspects of this condition.

PMID- 15948556
TI  - A case of metastatic epithelioid angiosarcoma in the lamina propria of a sigmoid
      tubulovillous adenoma.
AB  - Epithelioid angiosarcoma is an extremely rare tumor. It is generally a secondary
      tumor and the preferred sites of such metastases are the heart, pericardium,
      lung, breast, liver, spleen, bone, and brain. In rare cases the lung has been
      described as the primary site. The prognosis of this neoplasm is extremely poor.
      We report a case of epithelioid angiosarcoma with multiple bilateral lung
      infiltration, bone metastasis, and metastasis of the lamina propria of a
      tubulovillous adenoma of the colon.

PMID- 15948561
TI  - Alternative therapies in the treatment of headache in childhood, adolescence and
      adulthood.
AB  - In recent years, it has become common practice, in the treatment of headache, to
      use alternative methods, both alone and in association with drug therapies.
      Alternative therapies would appear to be more indicated in certain subjects:
      patients opposed to pharmacological treatments, those showing low tolerance of
      drugs or with a history of drug abuse, and those presenting medical
      contraindications or poor response to certain drugs. Numerous studies of
      alternative therapies have been published and here we review the literature data
      on the topic, considering in particular the accuracy of the various study methods
      in evaluating the effectiveness of the different therapies and their specificity
      for the different forms of headache. Specialists involved in the assessment and
      care of headache patients should strive to increase their knowledge of
      alternative therapies, so as to be better equipped to guide patients towards
      safe, economical and potentially effective treatments, rather than useless,
      costly or dangerous ones.

PMID- 15948562
TI  - Symmetrical intracerebral and intracerebellar calcification ("Fahr's disease").

PMID- 15948563
TI  - Pain fibers contribute to the generation of subcortical somatosensory evoked
      potentials (SEPs) in rats.
AB  - Subcortical somatosensory evoked potentials (SEPs) were obtained by electrical
      stimulation of the volar surface of the forepaw and were recorded from the skull
      overlying the contralateral somatosensory area of the cerebral cortex. Three
      distinct peaks were discernable in the SEPs prior to the first cortical
      component. Dorsal column transection at C3 level reduced the amplitude of
      component III by 48.7 +/- 4.7% without affecting the amplitude of components I
      and II. Morphine given either i.v. (2.5 mg/kg) or intrathalamically (25
      microg/kg) almost completely abolished the part of component III that remained
      after surgical sectioning of the dorsal column of the spinal cord. The effects of
      morphine were reversed by i.v. naloxone (0.25 mg/kg). These results indicate that
      both the dorsal column and the anterolateral systems contribute significantly to
      the generation of component III of subcortical SEPs. Subcortical SEPs may be a
      useful non-invasive technique for studying the neurophysiological effects of
      known and experimental analgesics.

PMID- 15948564
TI  - Acute effects of subclinical epileptiform EEG discharges on cognitive activation.
AB  - In this prospective, open, clinical comparative study we analyzed impairments of
      cognitive activation occurring during, immediately before and immediately after
      epochs with epileptiform EEG discharges of 3 seconds or longer, in an attempt to
      establish whether cognitive slowing occurs in direct association with an epoch
      with epileptiform EEG discharges and whether cognitive impairments precede or
      follow such an epoch. All children were assessed with EEG/video (Brainlab)
      simultaneously with computerized neuropsychological testing (FePsy): a test for
      cognitive activation (simple visual and auditory reaction time measurement).
      Thirty-seven epochs with epileptiform EEG discharges without clinical signs of a
      seizure (subclinical epileptiform EEG discharges) were evaluated. The results
      showed a statistically significant and clinically relevant slowing (35% compared
      to the overall reaction time), occurring during the epoch with epileptiform EEG
      discharges (repeated measurement analysis of variance p = < .05; df = 3; F-value:
      3.293). No statistically significant slowing was found for the periods 'post
      discharge' or 'pre-discharge'. Type of discharge was important and effects on
      cognitive activation were found exclusively for generalized discharges. This
      effect was, however, also seen in the remaining period, outside the 'peri
      discharge' periods and thus seemed to represent a more general effect of the type
      of epilepsy on cognitive activation. Our results show that the acute effect of
      short epileptiform EEG discharges (duration 4.14 sec; sd 1.38) may be impressive,
      causing impairment (slowing) of cognitive activation. This effect was limited to
      generalized discharges. This effect was not observed for focal discharges, even
      during longer periods with discharges. However, it is reassuring that this impact
      on cognitive activation is limited to the actual period in which the discharges
      occur and does not have 'post-discharge' effects. The risk of accumulating
      effects that may have longer-lasting repercussions on higher-order cognitive
      functions therefore seems to be negligible.

PMID- 15948565
TI  - Migraine with and without aura: electrophysiological and functional neuroimaging
      evidence.
AB  - The neuropathological processes believed to underlie migraine with and without
      aura are still widely debated in the literature. In order to arrive at a more
      detailed and comprehensive picture of the altered processes present in
      migraineurs, electrophysiological data obtained through transcranial magnetic
      stimulation (TMS) and electroencephalography (EEG) were combined with
      haemodynamic data obtained through functional magnetic resonance imaging (fMRI).
      Ten subjects affected by migraine (with or without aura) underwent TMS and EEG
      investigation prior to a visual stimulation task, studied in fMRI. Our
      preliminary results showed a reduced cortical silent period especially in
      subjects affected by migraine with aura. The fMRI BOLD response was found to be
      weaker in occipital areas proportionally to the frequency and severity of
      migraine attacks. The data obtained from our study seem to support the theory of
      cortical spreading depression recently observed in human subjects. Moreover, the
      electrophysiological data were also correlated to migraine attack frequency, thus
      pointing to elevated cortical excitability between attacks. Better understanding
      of the neuropathological processes that trigger migraine attacks will help in the
      selection of more adequate prophylactic therapies. The results of this
      preliminary study need to be confirmed in a a large sample of subjects.

PMID- 15948566
TI  - Unusual association of neurofibromatosis type 1 and coeliac disease in a single
      patient.
AB  - Twenty-five per cent of patients with neurofibromatosis type 1 (NF1) have
      gastrointestinal involvement and malabsorption symptoms have been reported. We
      describe, for the first time, a patient with NF1, in whom gastrointestinal
      symptoms were due to coeliac disease (CD). Although this could be a coincidental
      association, we suggest that CD should be taken into account in the differential
      diagnosis of diarrhoea occurring in NF1 patients.

PMID- 15948567
TI  - Crocodile tears syndrome: botulinum toxin treatment under EMG guidance.
AB  - Crocodile tears syndrome is one of the rare complications of facial paralysis.
      There have been several reports of cases in which botulinum toxin was found to be
      useful in the treatment of crocodile tears syndrome. The adverse effects, due to
      the paralytic action of botulinum toxin, have been reported to involve the
      palpebral muscle, lateral rectus and superior rectus. Therefore, we considered
      that it might be more appropriate to carry out the injection procedure under
      electromyographic guidance in order to inject botulinum toxin selectively into
      the lacrimal gland and protect the above-mentioned muscles. In conclusion, we
      recommend EMG guidance in the treatment of crocodile tears syndrome with
      botulinum toxin.

PMID- 15948569
TI  - [Worries about the care in nursing homes: beyond the nursing home].

PMID- 15948568
TI  - The immunobiology of malignant gliomas.
AB  - In spite of continuing advances in surgery, radiotherapy and chemotherapy, the
      last few decades have brought little improvement in the prognosis of malignant
      brain tumours. New immunotherapeutic strategies are being studied in numerous
      laboratories throughout the world in an effort to gather the further clinical and
      biological data needed in order to render these therapies effective and
      selective. The authors review recent advances in understanding of the
      immunobiology of brain tumours, in particular malignant gliomas. The biological
      basis of the interaction between nervous system cells and cancer cells is still
      an unresolved question and a constantly evolving area of research. Particular
      attention is paid to interleukin-2, one of the few effective cytokines used in
      the adjuvant treatment of some tumours. However, there is still a long way to go
      before these and other immunological approaches can be considered really
      applicable in the treatment of malignant gliomas.

PMID- 15948570
TI  - ["As long as you're healthy and have your husband". An empirical analysis of the
      personal well-being of 75-year olds in Flanders].
AB  - Using data from a 2002 representative survey of Flemish 75-year olds (N = 1457),
      the aim of the present study is to identify the structures in and causes of
      subjective well-being. The analyses reveal the great importance of good health.
      Respondents with a good physical and mental condition, who have a great deal of
      functional mobility and independence, do feel much better. Secondly, findings
      indicate that respondents who faced the loss of their partner, experience lower
      well-being. This explains the found gender differences. Women have lower
      perceived quality of life, mainly because of their greater susceptibility to
      widowhood. Furthermore, missing the former job and work role also contributes to
      lower levels of well-being. Finally, respondents who can cope financially, who
      feel satisfied with their social contacts and who spend their time in an active
      way, have higher personal well-being.

PMID- 15948572
TI  - [The final phase of dementia in a group of nursing home patients: prevalence and
      characteristics].
AB  - There is scant literature about patients in the final phase of dementia. Uniform
      terminology and operational definition of the final phase of dementia is lacking.
      Furthermore, it is difficult to monitor these patients because existing
      assessment scales face bottom- or ceiling effects in this population. The aim of
      this study was to assess the prevalence and the characteristics of patients in
      the final phase of dementia in a group of 210 Dutch nursing home patients with
      dementia. Stage 7 of the Global Deterioration Scale of Reisberg et al. was used
      to operationally define the final phase of dementia. All patients were scored on
      a self-constructed assessment scale. Furthermore, treatment aspects and advance
      directives were registered.

PMID- 15948573
TI  - [Hyperthyroidism in the elderly: aspecific signs may cause a delay in diagnosis].
AB  - The clinical manifestations of thyroid diseases in the elderly are often atypical
      and can easily be attributed to other medical conditions or 'normal aging'. Two
      nursing home patients with hyperthyroidism are described. Due to the atypical
      presentation of the thyroid disease their complaints were attributed to other
      conditions. In both patients there was a significant delay in diagnosis and
      treatment of hyperthyroidism. In elder patients signs and symptoms of
      thyreotoxicosis are frequently related to cardiovascular, gastrointestinal and
      neuropsychiatric disorders. Most often occur atrial fibrillation, worsening of
      cardiac failure and angina pectoris, weight loss, anorexia, constipation,
      cognitive impairment and delirium. Delay of diagnosis and treatment of
      hyperthyroidism may be potentially harmful to the patient. Untreated
      thyreotoxicosis may lead to serious cardiovasculair complications (particularly
      cardiac failure and cerebrovascular accidents), mental deterioration and
      osteoporosis. In elder people with unexplained and vague signs and symptoms
      thyroid function should always be checked. The TSH assay is a very accurate
      diagnostic test for screening thyroid function. A normal TSH indicates
      euthyroidism with an accuracy of almost 100%. The medical treatment for
      hyperthyreoidism in the elderly are antithyroid drugs. When an euthyroid state is
      rendered, suppletion with L-thyroxine may be nessecary. Radioactive iodine
      treatment is preferred in some cases though there may be practical difficulties
      with the application of this treatment in nursing home patients because temporary
      isolation is necessary.

PMID- 15948574
TI  - OSMA and Oklahoma medicine: 1906-1915.

PMID- 15948575
TI  - Putting prevention into practice. Part II: Counseling patients to quit smoking.
AB  - Today, heart disease and cancer cause more death and disability in Oklahoma and
      the United States than all other causes combined. Over 400,000 of these deaths
      are directly attributable to tobacco use each year. While the majority of smokers
      want to quit, the smoking habit is particularly difficult to change because of
      the addictive properties of nicotine. Consistent and reliable recommendations and
      assistance delivered by a trusted medical provider can support and empower
      patients to quit tobacco use or maintain their non-smoking status. Properly
      assessing and triaging a patient's readiness to quit smoking allows you to
      provide appropriate information to individuals at all different stages on the
      readiness-to-change spectrum. A brief query can set the stage for future
      interactions and move a smoker towards action to quit. Utilize support staff and
      systems interventions, such as chart reminders and protocols, so the provider can
      focus encounter time on the 3 A's of ASK, ADVISE, and ASSIST.

PMID- 15948576
TI  - The Oklahoma Attorney General's Task Force report on the State of End-of-Life
      Health Care, 2005.
AB  - This article includes the recommendations submitted by the 15 members of the
      Oklahoma Attorney General's Task Force in their Report on the State of End-of
      Life Health Care. The task force was created on April 21, 2004, and their report
      was accepted by Attorney General W.A. Drew Edmondson at a press conference April
      11, 2005. It has been forwarded to members of the Oklahoma Legislature, relevant
      state agencies and organizations with an invitation to join with members of the
      task force to continue efforts to improve end-of-life care for Oklahomans. Copies
      of the report are available upon request to the Office of Attorney General.

PMID- 15948577
TI  - Compliance update--valid types of signatures in this modern era.
AB  - Proper signatures in the medical record is an area of concern because they are
      included in the Office of Inspector General (OIG) Compliance Guidance as a
      potential risk area effecting physician practices. One of the four areas
      identified by OIG is timely, accurate and complete documentation, which includes
      "date and legible identity of the observer." Federal auditors deny claims and
      require refunds if signatures are omitted from documentation of services. The
      vision of the current President is for all Americans to have Electronic Health
      Records (EHR) within a decade; this implies a growing use of electronic
      signatures. What constitutes a valid signature, and what regulations affect the
      use and type of signature? Businesses require signatures on many forms and
      documents. However, what if a check is not signed; can it be cashed? If a
      contract is not signed, is it binding? Similarly, if the medical record is not
      signed, will it withstand scrutiny in court? What is the significance of a
      signature? How important is it to authenticate or sign a report? To authenticate
      means to verify that the message/report comes from its stated source; therefore
      the author stands behind the documentation as written. The type of signature that
      is acceptable is variable, depending on the facility and the form payer requires.

PMID- 15948578
TI  - Assessing and managing biological risks of plants used for bioremediation,
      including risks of transgene flow.
AB  - The plants used for phytoremediation pose special biological risks, whether
      transgenic or not, as most of the species: (a) are semi-domesticated; (b) are
      introduced from other habitats; (c) can become established in the contaminated
      site; (d) can spread and displace native species, and/or; (e) may introgress
      transgenes into related species. The addition of transgenes can reduce the risks,
      e.g. to sterilize or render the species and hybrid offspring hypersensitive to
      environmental effects (heat, cold), or to a chemical that will cull the species.
      Various measures can contain transgenes used in phytoremediation species to
      prevent gene flow, but most containment technologies are both uni-directional
      (prevent either outflow or influx), and are inherently leaky, even a concept
      specifically utilizable for phytoremediation--grafting non-transgenic scions on
      bioremediating transgenic rootstocks. Containment mechanisms should be either
      stacked with each other or with "mitigator" genes. Transgenic mitigation (TM) has
      mitigator genes added in tandem to the desired primary transgene (genetically
      linked) and the mitigator genes confer traits that are positive or neutral to the
      desired species but are deleterious to hybrids, keeping them at very low
      frequencies. The concept was demonstrated in tobacco and oilseed rape with a
      dwarfing mitigator gene that enhanced the reproductive productivity (harvest
      index) when cultured alone, but eliminated it from mixed populations. Besides the
      mitigator genes previously proposed for crop species (sterility, no seed
      shattering, dwarfing, no secondary dormancy) there are genes especially
      appropriate for phytoremediation, e.g. overexpression of cytokinin oxidase
      (reduces cytokinin levels) conferring reduced shoot systems (unfitness to
      compete) with a more extensive root system that is better for extracting toxic
      wastes as well as no-flowering for vegetatively propagated species. Thus,
      biotechnology can be harnessed to reduce risks from both non-transgenic and
      transgenic phytoremediation species.

PMID- 15948579
TI  - A ligand function of glutathione S-transferase.
AB  - Glutathione S-transferases (GSTs) are ubiquitous enzymes and abundant in plants.
      They are intimately involved in plant metabolism and stress defense related to
      reactive oxygen species. Our project assigned particular reactions including
      novel ones to certain GST-isoforms. Transformed E. coli was used to express
      recombinant GST-isoforms from maize. An N-terminal His tag allowed their
      purification by affinity chromatography. Three GST-monomers had a molecular
      weight of 26, 27, 29 kDa, and aggregated to dimers when assayed for their enzymic
      properties. Four dimeric isoforms were used to study how they interact with
      tetrapyrroles (of the chlorophyll biosynthesis pathway). It was found that
      protoporphyrin IX (Proto IX), Mg-protoporphyrin and other tetrapyrroles are bound
      non-covalently ("liganded") to GSTs but not conjugated with reduced glutathione.
      This binding is non-covalent, and results in inhibition of conjugation activity,
      the degree depends on type of the porphyrin and GST-isoform. I50-values between 1
      10 microM were measured for Proto IX, the inhibition by mesoporphyrin and Mg
      protoporphyrin was 2- to 5-fold less. The ligand binding is noncompetitive for
      the substrate 1-chloro-2,4-dinitrobenzene and competitive for glutathione. The
      dimer GST 26/26 prevents the (non-enzymic) autoxidation of protoporphyrinogen to
      Proto IX, which produces phytotoxic reactive oxygen species in the light. GST
      27/27 protects hemin against degradation. Protoporphyrinogen is formed in the
      plastid and then exported into the cytosol. Apparently binding by a suitable GST
      isoform ensures that the highly autoxidizable protoporphyrinogen can safely reach
      the mitochondrium where it is processed to cytochrome.

PMID- 15948580
TI  - Short transcript-derived fragments from the metal hyperaccumulator model species
      Arabidopsis halleri.
AB  - Phytoremediation of metal contaminated soils requires high-biomass plants
      exhibiting tolerance to and accumulation of metal contaminants. However, very
      little is known about the genes controlling these traits. In order to better
      understand this, Arabidopsis halleri ssp. halleri (L.) O'Kane and Al-Shehbaz, a
      naturally selected zinc and cadmium tolerant plant species capable of
      hyperaccumulating both metals, is a suitable model plant. To date, the scarcity
      of sequence information from A. halleri is still limiting its use as a model
      organism. Here we report 128 transcript-derived sequence fragments (TDFs)
      identified in a cDNA-AFLP approach aimed at identifying metal-regulated
      transcripts in roots. In addition we show that in roots of A. halleri, transcript
      levels of AhPDR11, encoding an ATP-binding-cassette (ABC) transport protein, are
      slightly induced in response to metal exposure.

PMID- 15948581
TI  - Phase I xenobiotic metabolic systems in plants.
AB  - Phytoremediation uses living higher plants for the removal and biochemical
      decomposition of environmental pollutants. In this paper Phase I metabolic
      pathways in the biotransformation reactions of organic pollutants in plants are
      reviewed. These reactions result in the introduction of functional groups in the
      xenobiotic molecule or the exposure of preexisting functional groups and lead to
      the formation of more polar, more water-soluble, chemically more reactive and
      sometimes biologically more active derivatives. Phase I type reactions are most
      important in the phytoremediation of hydrophobic, chemically stable organic
      pollutants, such as polycyclic aromatic hydrocarbons and (poly)chlorinated
      aliphatic and aromatic hydrocarbons. Although Phase I reactions involve a wide
      range of chemical transformations from hydrolysis to reduction, oxidative
      processes catalyzed by cytochrome P450 containing monooxygenases are the most
      important. Transgenic plants with tailored Phase I enzymatic activities may play
      major roles in the removal of environmentally stable organic pollutants from
      contaminated fields.

PMID- 15948582
TI  - Relay cropping for improved air and water quality.
AB  - Using plants to extract excess nitrate from soil is important in protecting
      against eutrophication of standing water, hypoxic conditions in lakes and oceans,
      or elevated nitrate concentrations in domestic water supplies Global climate
      change issues have raised new concerns about nitrogen (N) management as it
      relates to crop production even though there may not be an immediate threat to
      water quality. Carbon dioxide (CO2) emissions are frequently considered the
      primary cause of global climate change, but under anaerobic conditions, animals
      can contribute by expelling methane (CH4) as do soil microbes. In terms of the
      potential for global climate change, CH4 is approximately 25 times more harmful
      than CO2. This differential effect is minuscule compared to when nitrous oxide
      (N2O) is released into the atmosphere because it is approximately 300 times more
      harmful than CO2. N2O losses from soil have been positively correlated with
      residual N (nitrate, NO3-) concentrations in soil. It stands to reason that
      phytoremediation via nitrate scavenger crops is one approach to help protect air
      quality, as well as soil and water quality. Winter wheat was inserted into a seed
      corn/soybean rotation to utilize soil nitrate and thereby reduce the potential
      for nitrate leaching and N2O emissions. The net effect of the 2001-2003 relay
      cropping sequence was to produce three crops in two years, scavenge 130 kg N/ha
      from the root zone, produce an extra 2 Mg residue/ha, and increase producer
      profitability by approximately 250 dollars/ha.

PMID- 15948583
TI  - Using hyperaccumulator plants to phytoextract soil Ni and Cd.
AB  - Two strategies of phytoextraction have been shown to have promise for practical
      soil remediation: domestication of natural hyperaccumulators and bioengineering
      plants with the genes that allow natural hyperaccumulators to achieve useful
      phytoextraction. Because different elements have different value, some can be
      phytomined for profit and others can be phytoremediated at lower cost than soil
      removal and replacement. Ni phytoextraction from contaminated or mineralized
      soils offers economic return greater than producing most crops, especially when
      considering the low fertility or phytotoxicity of Ni rich soils. Only soils that
      require remediation based on risk assessment will comprise the market for
      phytoremediation. Improved risk assessment has indicated that most Zn + Cd
      contaminated soils will not require Cd phytoextraction because the Zn limits
      practical risk from soil Cd. But rice and tobacco, and foods grown on soils with
      Cd contamination without corresponding 100-fold greater Zn contamination, allow
      Cd to readily enter food plants and diets. Clear evidence of human renal tubular
      dysfunction from soil Cd has only been obtained for subsistence rice farm
      families in Asia. Because of historic metal mining and smelting, Zn + Cd
      contaminated rice soils have been found in Japan, China, Korea, Vietnam and
      Thailand. Phytoextraction using southern France populations of Thlaspi
      caerulescens appears to be the only practical method to alleviate Cd risk without
      soil removal and replacement. The southern France plants accumulate 10-20-fold
      higher Cd in shoots than most T. caerulescens populations such as those from
      Belgium and the UK. Addition of fertilizers to maximize yield does not reduce Cd
      concentration in shoots; and soil management promotes annual Cd removal. The
      value of Cd in the plants is low, so the remediation service must pay the costs
      of Cd phytoextraction plus profits to the parties who conduct phytoextraction.
      Some other plants have been studied for Cd phytoextraction, but annual removals
      are much lower than the best T. caerulescens. Improved cultivars with higher
      yields and retaining this remarkable Cd phytoextraction potential are being bred
      using normal plant breeding techniques.

PMID- 15948584
TI  - Phytoremediation with transgenic trees.
AB  - In the present paper actual trends in the use of transgenic trees for
      phytoremediation of contaminated soils are reviewed. In this context a current
      field trial in which transgenic poplars with enhanced GSH synthesis and hence
      elevated capacity for phytochelatin production are compared with wildtype plants
      for the removal of heavy metals at different levels of contamination and under
      different climatic conditions. The studies are carried out with grey poplar
      (Populus tremula x P. alba), wildtype plants and plants overexpressing the gene
      for gamma-glutamylcysteine synthetase (gshI) from E. coli in the cytosol. The
      expression of this gene in poplar leads to two- to four-fold enhanced GSH
      concentrations in the leaves. In greenhouse experiments under controlled
      conditions these transgenic poplars showed a high potential for uptake and
      detoxification of heavy metals and pesticides. This capacity is evaluated in
      field experiments. Further aims of the project are to elucidate (a) the stability
      of the transgene under field conditions and (b) the possibility of horizontal
      gene transfer to microorganisms in the rhizosphere. The results will help to
      assess the biosafety risk of the use of transgenic poplar for phytoremediation of
      soils.

PMID- 15948585
TI  - Volatile organic compound fate in phytoremediation applications: natural and
      engineered systems.
AB  - Unique sampling techniques have generated a new understanding regarding the fate
      of volatile organic compounds (VOCs) in phytoremediation systems. Tissue sampling
      and diffusion traps were used to determine how VOCs are transported in and
      diffuse from vegetation, particularly woody species. These techniques were then
      utilized to observe how plants interact with different contaminated media,
      showing transport of contaminants occurs from the vadose zone (vapor phase) as
      well as the saturated zone (aqueous phase). Data was gathered in laboratory
      studies, in native vegetation, and in engineered phytoremediation systems. The
      findings reveal that diffusion from the xylem tissues to the atmosphere is a
      major fate for VOCs in phytoremediation applications. Linking VOCs' fate with
      groundwater hydraulics, mass removal rates from contaminant plumes can be
      estimated. These techniques were also utilized to observe the impact of
      engineered plant/microbe systems, which utilize recombinant, root-colonizing
      organisms to selectively degrade compounds and subsequently alter the fate of
      VOCs and other organic compounds. The genetically enhanced rhizoremediation
      methods pose a novel approach that may allow for biodegradation of compounds that
      formerly were considered recalcitrant.

PMID- 15948586
TI  - Transcription profiling of the metal-hyperaccumulator Thlaspi caerulescens (J. &
      C. PRESL).
AB  - Thlaspi caerulescens is a well-studied metal-hyperaccumulator of zinc, cadmium
      and nickel, belonging to the Brassicaceae family. Moreover it is one of the few
      hyperaccumulators that occur on different metalliferous soil types, as well as on
      nonmetalliferous soils. We are interested in the development of systems to
      improve phytoremediation of metal contaminated soils through improved metal
      accumulation. About 1900 cDNAs isolated from T. caerulescens roots were
      hybridized with reverse transcribed RNA from zinc-treated T. caerulescens plants
      of two accessions originating from two different soil types. This comparative
      transcript profiling of T. caerulescens plants resulted in the identification of
      genes that are affected by heavy metals. The developed microarray proved to be an
      appropriate tool for a large scale analysis of gene expression in this metal
      accumulator species.

PMID- 15948587
TI  - Adaptative evolution of metallothionein 3 in the Cd/Zn hyperaccumulator Thlaspi
      caerulescens.
AB  - Laboratoire de Physiologie et Genetique Moleculaire des Plantes, Universite Libre
      de Bruxelles, Campus Plaine (CP 242) Bd du triomphe, B-1050 Brussels, Belgium.

PMID- 15948588
TI  - Identification of metalliferous ecotypes of Cistus ladanifer L. using RAPD
      markers.
AB  - The genetic diversity of Cistus ladanifer ssp. ladanifer (Cistaceae) growing on
      ultramafic and non-ultramafic (basic and schists) soils in the NE of Portugal was
      studied in order to identify molecular markers that could distinguish the metal
      tolerant ecotypes of this species. Random Amplified Polymorphic DNA (RAPD)
      markers were used in order to estimate genetic variation and differences between
      populations. The RAPD dataset was analysed by means of a cluster analysis and an
      analysis of molecular variance (AMOVA). Our results indicate a significant
      partitioning of molecular variance between ultramafic and non-ultramafic
      populations of Cistus ladanifer, although the highest percentage of this variance
      was found at the intra-population level. Mantel's test showed no relationship
      between inter-population genetic and geographic distances. A series of RAPD bands
      that could be related to heavy metal tolerance were observed. The identification
      of such markers will enable the use of Cistus ladanifer in phytoremediation
      procedures.

PMID- 15948589
TI  - Plant screening of halophyte species for cadmium phytoremediation.
AB  - Chloride (Cl-) has been related to increased phytoavailability of cadmium (Cd) in
      soil. A glasshouse experiment using a historically contaminated soil was
      undertaken to evaluate the effect of chloride on Cd uptake by salt-tolerant
      plants and possibly quantify the uptake of discrete Cd species (e.g. Cd2+, CdCl+,
      CdCl(0)2). Chloride treatments were applied as 100 mM NaCl and compared with
      equivalent Na2SO4 treatments. Activities of Cd species in soil pore water were
      calculated using the WHAM-VI speciation model. Cadmium solubility and uptake by
      plants was generally enhanced by addition of chloride to soil. Good correlations
      were found between Cd uptake and concentrations of Cd chloride complexes in soil
      pore water.

PMID- 15948590
TI  - Factors affecting heavy metal uptake in plant selection for phytoremediation.
AB  - The heavy metal uptake of ten plant species was studied under different soil and
      climatic conditions. Effects of soil pH, temperature, plant species and
      phenophase on the heavy metal content of stems and leaves were determined in pot
      experiments. Plants and soil samples were collected from a lead/zinc mine ore
      (Gyongyosoroszi, Hungary) and characterised by high contents of Pb, Zn, As, Cd,
      Cu. The possibility of an adapted phytoremediation technology was indicated by
      different bioconcentration factors (BCF). The BCF depended markedly (10- to 100
      fold) on plant species and environmental conditions. Based on our results a
      "season-adapted" phytoextraction technology with different plant species
      (utilising their different temperature requirements and/or harvest time) is
      suggested.

PMID- 15948591
TI  - Cadmium phytoextraction potential of poplar clones (Populus spp.).
AB  - Biomass production, leaf number and area, photosynthetic and dark respiration
      rates, leaf concentration of photosynthetic pigments, nitrate reductase activity,
      as well as cadmium concentrations in leaves, stem, and roots were measured in
      poplar clones PE 4/68, B-229, 665, and 45/51. Plants were grown hydroponically
      under controlled conditions and treated with two different cadmium (Cd)
      concentrations (10(-5) and 10(-7) M) in the same background solution (Hoagland's
      solution). The presence of Cd did not cause serious disturbance of growth and
      physiological parameters in the studied poplar clones. Cd concentrations in plant
      tissues reflected external concentrations. In treated plants, root contents
      increased from 38.57 to 511.51 ppm, leaf contents from 0.91 to 7.50, while stem
      contents ranged from 1.37 to 9.50 ppm.

PMID- 15948592
TI  - Isolation of mercury-binding peptides in vegetative parts of Chromolaena odorata.
AB  - Mercury-binding peptides from roots, stems, and leaves of Hg-treated Chromolaena
      odorata plants were isolated and partially characterized using RP-HPLC and ESI
      MS. Upon exposure of C. odorata plants to high concentrations of 1.0 and 2.0
      microM Hg(NO3)2 treatments from 0-28 days, they accumulated as much as 125 mg/g
      (dry wt) Hg in the roots, 15.280 mg/g (dry wt) Hg in the stems, and 0.800 mg/g
      (dry wt) Hg in the leaves indicating that C. odorata has a high potential as a
      phytoremediation agent of inorganic mercury. The plant's ability to accumulate
      and sequester Hg ions was primarily attributed to the production of Hg-binding
      peptides, which were initially detected through the use of Ellman's reagent.
      Isolation techniques using RP-HPLC equipped with a C18 column manifested a single
      prominent peak consistently appearing at a retention time of 2.6-2.8 min in all
      the plant samples treated with different Hg concentrations at varying lengths of
      exposure. Further characterization of this prominent peak using electrospray
      ionization mass spectrometry revealed the presence of a peptide containing
      several cysteine residues with the highest peak concentration recorded at 91 mV
      and 89 mV in roots and stems of plants treated with 2.0 microM Hg(NO3)2 for 4 wk
      (P < 0.05) and 85 mV in leaves treated with 1.0 microM Hg(NO3)2 for 1 wk.

PMID- 15948593
TI  - Leaching of microelement contaminants: a long-term field study.
AB  - A field experiment with microelement loads was set up on loamy textured,
      calcareous chernozem soil formed on loess. The ploughed layer contained ca. 5%
      CaCO3 and 3% humus. The soil was well supplied with Ca, Mg, Mn and Cu, moderately
      supplied with N and K, and weakly supplied with P and Zn. The water table is at
      the depth of 15 m, the water balance of the area is negative, and the site is
      drought sensitive. Salts of the 13 examined microelements were applied at 4 doses
      in the spring of 1991. Treatments were arranged in a split-plot design, in a
      total of 104 plots with two replications. Loading rates were 0, 90, 270 and 810
      kg/ha per element in the form of AlCl3, NaAsO2, BaCl2, CdSO4, K2CrO4, CuSO4,
      HgCl2, (NH4)6Mo7O24, NiSO4, Pb(NO3)2, Na2SeO3, SrSO4, ZnSO4. Soil profiles of the
      control and the 810 kg/ha treated plots were sampled in the 3rd, 6th and 10th
      year of the trial. The mixed samples, consisting of 5 cores/plot were taken in 30
      cm steps to 60 cm (year 1993), 90 cm (year 1996), and 290 cm (year 2000).
      Ammonium acetate + EDTA-soluble element content was determined. The main
      conclusions of the study are: (1) In soils contaminated with 810 kg/ha load rates
      As, Hg, Ni, Cu, Pb, Ba and Sr displayed no significant vertical movement. There
      is little uptake and translocation in plants of these elements: their
      concentration in the above-ground plant parts usually remains below 5-10 mg/kg
      dry mass with the exception of Ba and Sr showing a somewhat higher accumulation.
      Under our conditions the above elements did not behave as dangerous contaminants
      to the soil, groundwater, or plants. (2) Moderate leaching of Zn and Cd was
      detected when applied at higher doses. Their accumulation was also moderate in
      the above-ground plants parts. Zn is not a dangerous pollutant for soil, plants
      or groundwater at our site. Cd, however, is a very dangerous element because of
      its high toxicity to mammals, soil life and crops. (3) Cr, Se, and Mo (in the
      form of chromate, selenate and molybdenate anions) exhibited great mobility in
      the soil and partly in the soil-plant system. Cr was hardly detectable in the
      above-ground parts of plants. Still, its rapid leaching can jeopardize
      groundwater quality. Se was strongly accumulated in all plant organs and was
      highly toxic for all crops. Mo, too, showed 2-3 orders of magnitude greater
      accumulation in plant parts, resulting in products unfit for animal or human
      consumption. Under our experimental conditions Cr(VI), Se, Mo can be classified
      as dangerous contaminants, since the anion forms remained stabile for a long time
      in this well-aerated calcareous environment.

PMID- 15948594
TI  - Novel metabolism of nitrogen in plants.
AB  - Our previous study showed that approximately one-third of the nitrogen of 15N
      labeled NO2 taken up into plants was converted to a previously unknown organic
      nitrogen (hereafter designated UN) that was not recoverable by the Kjeldahl
      method (Morikawa et al., 2004). In this communication, we discuss metabolic and
      physiological relevance of the UN based on our newest experimental results. All
      of the 12 plant species were found to form UN derived from NO2 (about 10-30% of
      the total nitrogen derived from NO2). The UN was formed also from nitrate
      nitrogen in various plant species. Thus, UN is a common metabolite in plants. The
      amount of UN derived from NO2 was greatly increased in the transgenic tobacco
      clone 271 (Vaucheret et al., 1992) where the activity of nitrite reductase is
      suppressed less than 5% of that of the wild-type plant. On the other hand, the
      amount of this UN was significantly decreased by the overexpression of S
      nitrosoglutathione reductase (GSNOR). These findings strongly suggest that
      nitrite and other reactive nitrogen species are involved in the formation of the
      UN, and that the UN-bearing compounds are metabolizable. A metabolic scheme for
      the formation of UN-bearing compounds was proposed, in which nitric oxide and
      peroxynitrite derived from NO2 or endogenous nitrogen oxides are involved for
      nitrosation and/or nitration of organic compounds in the cells to form nitroso
      and nitro compounds, including N-nitroso and S-nitroso ones. Participation of non
      symbiotic haemoglobin bearing peroxidase-like activity (Sakamoto et al., 2004)
      and GSNOR (Sakamoto et al., 2002) in the metabolism of the UN was discussed. The
      UN-bearing compounds identified to date in the extracts of the leaves of
      Arabidopsis thaliana fumigated with NO2 include a delta2-1,2,3-thiadiazoline
      derivative (Miyawaki et al., 2004) and 4-nitro-beta-carotene.

PMID- 15948595
TI  - Tolerance to, and uptake and degradation of 2,4,6-trinitrotoluene (TNT) are
      enhanced by the expression of a bacterial nitroreductase gene in Arabidopsis
      thaliana.
AB  - Arabidopsis thaliana was transformed with a gene encoding a nitroreductase (NTR,
      E.C.1.6.99.7) with activity against a wide range of nitroaromatic compounds. The
      gene was transferred from Escherichia coli by an Agrobacterium-mediated in planta
      method. The obtained seeds were sowed to produce T1 plants, and they were assayed
      for the integration of the transgene in the plant genome. Transgenic plants that
      were positive with the PCR analysis were self-pollinated to produce T2 generation
      plants. Seven lines obtained were assayed for the NTR activity. While the non
      transformed wild-type plants showed no detectable NTR activity, the enzyme
      activity of the transgenic plant lines was approx. 20 times higher. Using the
      line with the highest NTR activity, the phytoremediation characteristics of
      plants against 2,4,6-trinitrotoluene (TNT) was investigated. While the wild-type
      plants did not grow in the presence of 0.1 mM TNT, the transgenic plants grew
      almost normally in this condition. The uptake of TNT by seedlings of transgenic
      plants increased by 7 to 8 times when theywere floated on TNT solution. HPLC
      analysis showed that the peak due to TNT taken upinto plant body was much smaller
      in the transgenic plants as compared with that of the wild type, and that a
      number of peaks attributable to the degradation products of TNT, including 4
      amino-2,6-dinitrotoluene, were detected in the extract from the transgenic
      plants. This indicates that the expression of bacterial NTR improved the
      capability of plants to degrade TNT.

PMID- 15948596
TI  - Nocturnal uptake and assimilation of nitrogen dioxide by C3 and CAM plants.
AB  - In order to investigate nocturnal uptake and assimilation of NO2 by C3 and
      crassulacean acid metabolism (CAM) plants, they were fumigated with 4 microl l(
      1) 15N-labeled nitrogen dioxide (NO2) for 8 h. The amount of NO2 and assimilation
      of NO2 by plants were determined by mass spectrometry and Kjeldahl-nitrogen based
      mass spectrometry, respectively. C3 plants such as kenaf (Hibiscus cannabinus),
      tobacco (Nicotiana tabacum) and ground cherry (Physalis alkekengi) showed a high
      uptake and assimilation during daytime as high as 1100 to 2700 ng N mg(-1) dry
      weight. While tobacco and ground cherry strongly reduced uptake and assimilation
      of NO2 during nighttime, kenaf kept high nocturnal uptake and assimilation of NO2
      as high as about 1500 ng N mg(-1) dry weight. Stomatal conductance measurements
      indicated that there were no significant differences to account for the
      differences in the uptake of NO2 by tobacco and kenaf during nighttime. CAM
      plants such as Sedum sp., Kalanchoe blossfeldiana (kalanchoe) and Aloe
      arborescens exhibited nocturnal uptake and assimilation of NO2. However, the
      values of uptake and assimilation of NO2 both during daytime and nighttime was
      very low (at most about 500 ng N mg(-1) dry weight) as compared with those of
      above mentioned C3 plants. The present findings indicate that kenaf is an
      efficient phytoremediator of NO2 both during daytime and nighttime.

PMID- 15948597
TI  - Genetic modification of wetland grasses for phytoremediation.
AB  - Wetland grasses and grass-like monocots are very important natural remediators of
      pollutants. Their genetic improvement is an important task because introduction
      of key transgenes can dramatically improve their remediation potential. Tissue
      culture is prerequisite for genetic manipulation, and methods are reported here
      for in vitro culture and micropropagation of a number of wetland plants of
      various ecological requirements such as salt marsh, brackish water, riverbanks,
      and various zones of lakes and ponds, and bogs. The monocots represent numerous
      genera in various families such as Poaceae, Cyperaceae, Juncaceae, and Typhaceae.
      The reported species are in various stages of micropropagation and Arundo donax
      is scaled for mass propagation for selecting elite lines for pytoremediation.
      Transfer of key genes for mercury phytoremediation into the salt marsh cordgrass
      (Spartina alterniflora) is also reported here. All but one transgenic lines
      contained both the organomercurial lyase (merB) and mercuric reductase (merA)
      sequences showing that co-introduction into Spartina of two genes from separate
      Agrobacterium strains is possible.

PMID- 15948598
TI  - Can tobacco have a potentially beneficial effect to our health?
AB  - With urgent pressure to clean up the contaminated environment, new approaches are
      needed. Phyto- and rhizoremediation using plants and related bacteria is a
      promising approach, but has its inborn limitations. To overcome the slow
      performance of the process, transgenic plants have been prepared specifically
      tailored for phytoremediation purposes. Our projects addressed a group of
      widespread synthetic organic xenobiotics, polychlorinated biphenyls (PCBs), and
      heavy metals as representatives of inorganic contaminants. Beside basic research
      studies in the field of phyto/rhizoremediation of the mentioned toxicants we
      focused on genetically modified plants as a highly promising tool for these
      purposes. We tried to prepare tobacco plants expressing the bacterial enzyme
      responsible for cleaving PCBs, coded by the gene bphC from the bacterial biphenyl
      operon. The expression of bphC product in fusion with the green fluorescent
      protein is described together with evaluation of the twice increased resistance
      of transgenic seeds towards PCBs. The other model is addressing improvement of
      cadmium accumulation by preparing plants bearing fused transgenes of metal
      binding protein (yeast metallothionein) with an introduced additional metal
      binding domain--polyhistidine anchor with high affinity to metals. The
      genetically modified plants exhibit 190% Cd accumulation of the control in
      harvestable parts, higher resistance and lower Cd content in roots. The
      performance of the plants in real contaminated soil is also evaluated.

PMID- 15948600
TI  - Differential induction of glutathione transferases and glucosyltransferases in
      wheat, maize and Arabidopsis thaliana by herbicide safeners.
AB  - By learning lessons from weed science we have adopted three approaches to make
      plants more effective in phytoremediation: (1) The application of functional
      genomics to identify key components involved in the detoxification of, or
      tolerance to, xenobiotics for use in subsequent genetic engineering/breeding
      programmes. (2) The rational metabolic engineering of plants through the use of
      forced evolution of protective enzymes, or alternatively transgenesis of
      detoxification pathways. (3) The use of chemical treatments which protect plants
      from herbicide injury. In this paper we examine the regulation of the xenome by
      herbicide safeners, which are chemicals widely used in crop protection due to
      their ability to enhance herbicide selectivity in cereals. We demonstrate that
      these chemicals act to enhance two major groups of phase 2 detoxification
      enzymes, notably the glutathione transferases and glucosyltransferases, in both
      cereals and the model plant Arabidopsis thaliana, with the safeners acting in a
      chemical- and species-specific manner. Our results demonstrate that by choosing
      the right combination of safener and plant it should be possible to enhance the
      tolerance of diverse plants to a wide range of xenobiotics including pollutants.

PMID- 15948599
TI  - AFLP analysis and improved phytoextraction capacity of transgenic gshI-poplar
      clones (Populus x canescens L.) for copper in vitro.
AB  - Clone stability and in vitro phytoextraction capacity of vegetative clones of P.
      x canescens (2n = 4x = 38) including two transgenic clones (ggs11 and lgl6) were
      studied as in vitro leaf disc cultures. Presence of the gshI-transgene in the
      transformed clones was detected in PCR reactions using gshI-specific primers.
      Clone stability was determined by fAFLP (fluorescent amplified DNA fragment
      length polymorphism) analysis. In total, 682 AFLP fragments were identified
      generated by twelve selective primer pairs after EcoRI-MseI digestion. Four
      fragments generated by EcoAGT-MseCCC were different (99.4% genetic similarity)
      which proves an unexpectedly low bud mutation frequency in P. x canescens. For
      the study of phytoextraction capacity leaf discs (8 mm) were exposed to a
      concentration series of ZnSO4 (10(-1) to 10(-5) M) incubated for 21 days on
      aseptic tissue culture media WPM containing 1 microM Cu. Zn2+ caused
      phytotoxicity only at high concentrations (10(-1) to 10(-2) M). The transgenic
      poplar cyt-ECS (ggs11) clone, as stimulated by the presence of Zn, showed
      elevated heavy metal (Cu) uptake as compared to the non-transformed clone. These
      results suggest that gshI-transgenic poplars may be suitable for phytoremediation
      of soils contaminated with zinc and copper.

PMID- 15948601
TI  - Detoxification of herbicides in Phragmites australis.
AB  - Unintentional loss of herbicides into drainage ditches, shores or other
      waterbodies may cause large problems in farmland. Therefore strategies for the
      phytoremediation of agrochemicals and especially herbicides have become a topic
      of great interest in many agricultural areas. However, in order to establish
      effective biological pollution control, information on the detoxification
      capacity of riparian plants and aquatic macrophytes (e.g., Phragmites australis)
      is important to build up effective buffer stripes. We determined the
      detoxification capacity of Phragmites australis roots and leaves for the
      conjugation of agrochemicals to glutathione by assaying the model substrate CDNB
      as well as the herbicides fenoxaprop-P, propachlor, pethoxamid and
      terbuthylazine. Specific GST activities were always higher in the rhizomes (6.78
      +/- 0.88 microkat/mg protein for CDNB) than in leaves (1.08 +/- 0.21 microkat/mg
      protein). The detoxification capacity is distributed across an array of GST
      isoforms. In summary, Phragmites australis seems to be efficient in herbicide
      detoxification and a good candidate for phytoremediation of effluents from
      agricultural sites.

PMID- 15948602
TI  - Mass balance studies of volatile chlorinated hydrocarbon phytoremediation.
AB  - In field-scale mass balance studies of poplar remediation of carbon tetrachloride
      (CT), more than 95% of the mass of CT was degraded with all of the CT chlorine
      accountable as chloride ion accumulation in the soil. Atmospheric loss of CT
      through leaf transpiration and trunk diffusion was insignificant. These findings
      are consistent with previously reported uptake and degradation of
      trichloroethylene (TCE) by poplar. Poplar phytoremediation of CT and TCE results
      in little decrease in aqueous concentration, since water is taken up at about the
      same rate as the chlorinated compounds. From this result we predict that
      phytoirrigation--the application of pumped contaminated groundwater to planted
      systems--will result in concentrations of the pollutants at the bottom of the
      root zone that are higher than permitted regulatory levels. Such plantations will
      be susceptible to loss of contaminants during rainfall events, possibly resulting
      in pollution of uncontaminated soil. Greenhouse studies of pollutant profiles in
      the media beneath poplar trees that were surface irrigated with TCE and CT
      confirmed that regulatory concentrations of these pollutants were not achieved in
      the root zone of the poplar; rather concentrations fell by less than 50%.

PMID- 15948603
TI  - Biodegrader metabolic expansion during polyaromatic hydrocarbons
      rhizoremediation.
AB  - Root-microbe interactions are considered to be the primary process of
      polyaromatic hydrocarbon (PAH) phytoremediation, since bacterial degradation has
      been shown to be the dominant pathway for environmental PAH dissipation. However,
      the precise mechanisms driving PAH rhizostimulation symbiosis remain largely
      unresolved. In this study, we assessed PAH degrading bacterial abundance in
      contaminated soils planted with 18 different native Michigan plant species.
      Phenanthrene metabolism assays suggested that each plant species differentially
      influenced the relative abundance of PAH biodegraders, though they generally were
      observed to increase heterotrophic and biodegradative cell numbers relative to
      unplanted soils. Further study of >1800 phenanthrene degrading isolates indicated
      that most of the tested plant species stimulated biodegradation of a broader
      range of PAH compounds relative to the unplanted soil bacterial consortia. These
      observations suggest that a principal contribution of planted systems for PAH
      bioremediation may be via expanded metabolic range of the rhizosphere bacterial
      community.

PMID- 15948604
TI  - Plant processes important for the transformation and degradation of explosives
      contaminants.
AB  - Environmental contamination by explosives is a worldwide problem. Of the 20
      energetic compounds, 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5
      triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) are
      the most powerful and commonly used. Nitroamines are toxic and considered as
      possible carcinogens. The toxicity and persistence of nitroamines requires that
      their fate in the environment be understood and that contaminated soil and
      groundwater be remediated. This study, written as a minireview, provides further
      insights for plant processes important for the transformation and degradation of
      explosives. Plants metabolize TNT and the distribution of the transformation
      products, conjugates, and bound residues appears to be consistent with the green
      liver model concept. Metabolism of TNT in plants occurs by reduction as well as
      by oxidation. Reduction probably plays an important role in the tolerance of
      plants towards TNT, and, therefore a high nitroreductase capacity may serve as a
      biochemical criterion for the selection of plant species to remediate TNT.
      Because the activities and the inducibilities of the oxidative enzymes are far
      lower than of nitroreductase, reducing processes may predominate. However,
      oxidation may initiate the route to conjugation and sequestration leading
      ultimately to detoxification of TNT, and, therefore, particularly the oxidative
      pathway deserves more study. It is possible that plants metabolize RDX also
      according to the green liver concept. In the case of plant metabolism of HMX, a
      conclusion regarding compliance with the green liver concept was not reached due
      to the limited number of available data.

PMID- 15948605
TI  - Rhizosphere-induced selenium precipitation for possible applications in
      phytoremediation of se polluted effluents.
AB  - Two bacterial isolates were obtained in axenic culture from the rhizosphere soil
      of Astragalus bisulcatus, a legume able to hyperaccumulate selenium. Both strains
      resulted of particular interest for their high resistance to the toxic oxyanion
      SeO3(2-) (selenite, Se(IV)). On the basis of molecular and biochemical analyses,
      these two isolates were attributed to the species Bacillus mycoides and
      Stenotrophomonas maltophilia, respectively. Their capability in axenic culture to
      precipitate the soluble, bioavailable and highly toxic selenium form selenite to
      insoluble and relatively non-toxic Se(0) (elemental selenium) was evaluated in
      defined medium added with 0.2 or 0.5 mM Se(IV). Both strains showed to completely
      reduce 0.2 mM selenite in 120 h, while 0.5 mM Se(IV) was reduced up to 67% of the
      initial concentration by B. mycoides and to about 50% by S. maltophilia in 48 h.
      Together in a dual consortium, B. mycoides and S. maltophilia increased the
      kinetics of selenite reduction, thus improving the efficiency of the process. A
      model system for selenium rhizofiltration based on plant-rhizobacteria
      interactions has been proposed.

PMID- 15948606
TI  - The arbuscular mycorrhizal status of poplar clones selected for phytoremediation
      of soils contaminated with heavy metals.
AB  - The aim of this work was to study the colonization of indigenous arbuscular
      mycorrhizal fungi (AMF) species in fine-roots of poplar clones. Roots of 7 poplar
      clones were sampled from a 1-year-old trial established at an industrial site
      strongly polluted with heavy metals at Balatonfuzfo, Hungary. The poplar clones
      have shown variable degrees of colonization by AMF, suggesting differential host
      susceptibility or mycorrhizal dependency. After outplanting the percentage of
      poplar survival was strongly correlated with the frequency of AMF infection. Two
      clones that survived at the lowest ratio after outplanting had not been colonized
      by AMF in contrast to those which survived to a much higher extent.

PMID- 15948607
TI  - Vegetation pattern and heavy metal accumulation at a mine tailing at
      Gyongyosoroszi, hungary.
AB  - Vegetation at an abandoned heavy metal bearing mine tailing may have
      multifunctional roles such as modification of water balance, erosion control and
      landscape rehabilitation. Research on the vegetation of mine tailings can provide
      useful information on tolerance, accumulation and translocation properties of
      species potentially applicable at moderately contaminated sites. Analyses of the
      relationship between heavy metal content (Pb, Zn and Cu) and vegetation in a mine
      tailing were carried out. These analyses included: (1) spatial analysis of
      relationship among heavy metal distribution, pH and vegetation patterns, and (2)
      analysis of heavy metal accumulation and translocation in some plant species.
      Presence of vegetation was found to be significantly dependent on pH value, which
      confirms that phytotoxicity is a function of element concentration in solution,
      which is primarily controlled by pH value in mine tailings. Among the most
      abundant plant species, dewberry (Rubus caesius), vipersbugloss (Echium vulgare),
      scarlet pimpernel (Anagallis arvensis) and narrowleaf plantain (Plantago
      lanceolata) accumulate significant amounts of Pb, Cu and Zn, while in the case of
      annual bluegrass (Poa annua) only Pb can be measured in elevated contents.
      Considering the translocation features, scarlet pimpernel, narrowleaf plantain,
      and dewberry accumulate heavy metals primarily in their roots, while heavy metal
      concentration in vipersbugloss and annual bluegrass is higher in the shoots.

PMID- 15948608
TI  - Short-term and working memory: past, progress, and prospects.

PMID- 15948609
TI  - The time course of response suppression: no evidence for a gradual release from
      inhibition.
AB  - Most models of serial recall postulate that recalled items are suppressed and
      thus temporarily rendered unavailable. Response suppression can explain several
      results, for example the small number of erroneous repetitions and people's
      reluctance to report repeated items. Although it is clear that response
      suppression is not permanent (thus permitting renewed recall of an item on the
      next trial), nothing is known about its time course. We report two experiments
      that measured the time course of response suppression with a multiple cued
      retrieval response-deadline method. Emphasis was on the extent of repetition
      inhibition for lists that contained a repeated item. Regardless of whether
      presentation was rapid (Experiment 1; 150 ms/item) or slow (Experiment 2; 500
      ms/item), (a) the standard pattern of repetition inhibition and erroneous
      repetitions occurred and (b) repetition inhibition remained constant across
      increasing retrieval time. This suggests that the release from response
      suppression is a discrete, list-wide effect rather than a continuous, gradual
      wearing off. The latter conclusion is consistent with the operation of the SOB
      model (Farrell & Lewandowsky, 2002) but not with models that postulate complete
      suppression with gradual wearing off.

PMID- 15948610
TI  - How is the serial order of a verbal sequence coded? Some comparisons between
      models.
AB  - Current models of verbal short-term memory (STM) propose various mechanisms for
      serial order. These include a gradient of activation over items, associations
      between items, and associations between items and their positions relative to the
      start or end of a sequence. We compared models using a variant of Hebb's
      procedure in which immediate serial recall of a sequence improves if the sequence
      is presented more than once. However, instead of repeating a complete sequence,
      we repeated different aspects of serial order information common to training
      lists and a subsequent test list. In Experiment 1, training lists repeated all
      the item-item pairings in the test list, with or without the position-item
      pairings in the test list. Substantial learning relative to a control condition
      was observed only when training lists repeated item-item pairs with position-item
      pairs, and position was defined relative to the start rather than end of a
      sequence. Experiment 2 attempted to analyse the basis of this learning effect
      further by repeating fragments of the test list during training, where fragments
      consisted of either isolated position-item pairings or clusters of both position
      item and item-item pairings. Repetition of sequence fragments led to only weak
      learning effects. However, where learning was observed it was for specific
      position-item pairings. We conclude that positional cues play an important role
      in the coding of serial order in memory but that the information required to
      learn a sequence goes beyond position-item associations. We suggest that whereas
      STM for a novel sequence is based on positional cues, learning a sequence
      involves the development of some additional representation of the sequence as a
      whole.

PMID- 15948611
TI  - Storage and retrieval of serial-order information.
AB  - In this paper I will first review some seminal work by Conrad on the storage and
      retrieval of serial-order information which is still very relevant today. Then I
      will discuss the TODAM (theory of distributed associative memory) approach to
      serial-order effects. I will compare the three TODAM serial-order models (the
      chaining model, the chunking model and the power-set model; Murdock, 1995) but
      concentrate on the power set model. Its original problems can be solved, but a
      revised and augmented version has some new problems. This paper is more of a
      progress report than a finished product, so the reader should be prepared to
      follow the twists and turns of the argument.

PMID- 15948612
TI  - Transposition asymmetry in immediate serial recall.
AB  - When participants confuse the position of items in immediate serial recall, they
      tend to recall transposed items too early rather than too late. This asymmetry of
      transposition errors was observed in four experiments. It increased as a function
      of list length, but was independent of report order, output position, cueing
      condition, and recall mode. The transposition asymmetry is consistent with error
      patterns in free recall and in regular speech production where transpositions are
      usually forward-looking. The asymmetry of transposition errors is discussed in
      terms of models of serial memory.

PMID- 15948613
TI  - Serial recall and presentation schedule: a micro-analysis of local
      distinctiveness.
AB  - According to temporal distinctiveness theories, items that are temporally
      isolated from their neighbours during presentation are more distinct and thus are
      recalled better. Event-based theories, which deny that elapsed time plays a role
      at encoding, explain isolation effects by assuming that temporal isolation
      provides extra time for rehearsal or consolidation of encoding. The two classes
      of theories can be differentiated by examining the symmetry of isolation effects:
      Event-based accounts predict that performance should be affected only by pauses
      following item presentation (because they allow time for rehearsal or
      consolidation), whereas distinctiveness predicts that items should also benefit
      from preceding pauses. The first experiment manipulated inter-item intervals and
      showed an effect of intervals following but not preceding presentation, in line
      with event-based accounts. The second experiment showed that the effect of
      following interval was abolished by articulatory suppression. The data are
      consistent with event-based theories but can be handled by time-based
      distinctiveness models if they allow for additional encoding during inter-item
      pauses.

PMID- 15948614
TI  - Sharpening the echo: an iterative-resonance model for short-term recognition
      memory.
AB  - We present an iterative-resonance model for recognition memory. On successive
      iterations, the probe is compared against a feature-by-feature profile of the
      study set. Yes decisions depend on the similarity of the probe to the profile; No
      decisions depend on a count of elements in the probe that are not in the profile.
      Successive iterations sharpen the evidence, and response latency is a function of
      the number of iterations needed to obtain a sufficiently clear result. The model
      successfully simulates classic data as well as recent data problematic for
      alternate models.

PMID- 15948615
TI  - Serial position curves in short-term memory: functional equivalence across
      modalities.
AB  - Four experiments investigated item and order memory for sequences of seen
      unfamiliar faces and heard nonwords. Experiments 1 and 3 found bowed serial
      position curves using the serial reconstruction test of order with faces and
      nonwords, respectively. Experiments 2 and 4 found limited recency, no primacy,
      and above chance performance on all items using a two-alternative forced choice
      (2AFC) test of item recognition, again with faces and nonwords. These results
      suggest that the different serial position curves typically found using
      traditional paradigms for exploring visual and verbal short-term memory are due
      to differences in the methods used rather than modality-specific mechanisms.

PMID- 15948616
TI  - Primacy and recency in nonword repetition.
AB  - An increasing body of evidence suggests that nonword repetition is related to
      immediate serial memory (e.g., Baddeley, Gathercole, & Papagno, 1998; Gathercole
      & Baddeley, 1993). One possible account of this relationship is that a nonword is
      processed like a list when it is first encountered. If this is the case, it
      should be possible to detect serial position effects in repetition of single
      nonwords. Three experiments tested this prediction. Experiment 1 examined whether
      there would be syllable serial position primacy and recency effects in repetition
      of polysyllabic nonwords, and obtained both primacy and recency effects.
      Experiments 2 and 3 showed that these effects were not due to the controlled
      duration of the nonwords or the requirements of concurrent articulation or the
      procedure by which nonwords were created.

PMID- 15948617
TI  - Word frequency effects in immediate serial recall: item familiarity and item co
      occurrence have the same effect.
AB  - In immediate serial recall, high-frequency words are better recalled than low
      frequency words. A prevalent interpretation of this effect suggests that, at the
      point of recall, degraded representations undergo a reconstruction process
      calling upon long-term knowledge of the to-be-remembered items. Recently, Stuart
      and Hulme (2000) following Deese (1960), suggested that high-frequency items are
      better recalled due to their better long-term associative links. Their results
      revealed that a familiarisation procedure involving repeated presentations of the
      to-be-remembered items in pairs abolished the usual frequency effect. In the
      experiment reported here, an alternative interpretation of this result is
      examined. Prior to the memory task, subjects received either no familiarisation,
      item familiarisation, or pair familiarisation. Both item and pair familiarisation
      improved the item recall of low-frequency items to the same extent, suggesting
      that increased familiarity can account for the co-occurrence effect.

PMID- 15948618
TI  - Overwriting of phonemic features in serial recall.
AB  - We tested two explanations of the phonological similarity effect in verbal short
      term memory: The confusion hypothesis assumes that serial positions of similar
      items are confused. The overwriting hypothesis states that similar items share
      feature representations, which are overwritten. Participants memorised a
      phonologically dissimilar list of CVC-trigrams (Experiment 1) or words
      (Experiment 2 and 3) for serial recall. In the retention interval they read aloud
      other items. The material of the distractor task jointly overlapped one item of
      the memory list. The recall of this item was impaired, and the effect was not
      based on intrusions from the distractor task alone. The results provide evidence
      for feature overwriting as one potential mechanism contributing to the
      phonological similarity effect.

PMID- 15948619
TI  - Forgetting and redintegration of consonants and vowels in pseudoword lists.
AB  - Immediate recall of phonemes was studied in a pseudoword span task. Finnish
      participants recalled lists of increasing length, consisting of
      C(consonant)V(vowel)CVCV pseudowords. The lists were made up from pools of 12
      pseudowords. There were three types of lists. In the non-redundant lists the
      items were unpredictable combinations of consonants and vowels. In consonant
      redundant lists, all items had the consonant frame /t/_/s/_/l/. In vowel
      redundant lists, all items had the vowel frame _/u/_/e/_/o/. Unlike redundant
      last syllables in a previous experiment, neither consonant nor vowel redundancy
      helped list recall. Instead, a harmful phonological similarity effect was
      apparent in the vowel-redundant case but not the consonant-redundant case. A
      phoneme-level analysis of recall showed that consonants were recalled better in
      consonant-redundant lists and vowels were recalled better in vowel-redundant
      lists compared to non-redundant lists. Vowels appeared to be more important for
      discrimination between items, with redundancy resulting in confusions. The
      consequences of phoneme-level forgetting and redintegration for item- and list
      level recall are discussed.

PMID- 15948620
TI  - Lexicality and phonological similarity: a challenge for the retrieval-based
      account of serial recall?
AB  - The retrieval-based account of serial recall (Saint-Aubin & Poirier, 2000)
      attributes lexicality, phonological similarity, and articulatory suppression
      effects to a process where long-term representations are used to reconstruct
      degraded phonological traces. Two experiments tested this assumption by
      manipulating these factors in the recall of four- and five-item lists of words
      and non-words. Lexicality enhanced item recall (IR), but only affected position
      accuracy (PA) for five-item lists under suppression. Phonological similarity
      influenced both words and non-words, and produced impaired PA in silent and
      suppressed conditions. Consistent with the retrieval-based account, words and non
      words of high word-likeness appear subject to redintegration. However, some
      findings, like suppression not reducing the phonological similarity impairment in
      suppressed conditions, present challenges for the retrieval-based account and
      other models of serial recall.

PMID- 15948621
TI  - Visual distraction and visuo-spatial memory: a sandwich effect.
AB  - The functional characteristics of visuo-spatial serial memory and its sensitivity
      to irrelevant visual information are examined in the present study, through the
      investigation of the sandwich effect (e.g., Hitch, 1975). The memory task was one
      of serial recall for the position of a sequence of seven spatially and temporally
      separated dots. The presence of irrelevant dots interpolated with to-be
      remembered dots affected performance over most serial positions (Experiment 1)
      but that effect was significantly reduced when the interpolated dots were
      distinct from the to-be-remembered dots by colour and shape (Experiment 2).
      Parallels are made between verbal and spatial serial memory, and the reduction of
      the sandwich effect is discussed in terms of the contribution of perceptual
      organisation and attentional factors in short-term memory.

PMID- 15948622
TI  - An item/order trade-off explanation of word length and generation effects.
AB  - The item-order hypothesis suggests that under certain conditions increased item
      processing can lead to deficits in order processing, and that this produces a
      dissociation in performance between item and order tasks. The generation effect
      is one such example. The word length effect is seen as another instance where
      this trade-off might be observed. The following experiments compare word length
      and generation effects under serial recall and single item recognition
      conditions. Short words are better recalled than long words on the serial recall
      task but long words were better recognised than short words. The results are
      consistent with the item-order approach and support a novel explanation for the
      word length effect.

PMID- 15948623
TI  - Is spoken duration a sufficient explanation of the word length effect?
AB  - The word length effect is one of the cornerstones of trace decay plus rehearsal
      models (TDR) of memory. Words of long spoken duration take longer to rehearse
      than words of short spoken duration and as such suffer more decay and are thus
      less well recalled. The current experiment manipulates both syllable length and
      spoken duration within words of fixed syllable length in an aim to test the
      assumptions of the TDR model. Our procedures produced robust effects of both
      syllable length and spoken duration in four measures of the time it takes to
      pronounce the different types of words. Serial recall for the same materials
      produced robust syllable effects, but no duration effects.

PMID- 15948624
TI  - Silent reading rate and memory span.
AB  - This paper reports two experiments concerned with the form of the linear function
      relating memory span to pronunciation rate. Experiment 1 asked whether the
      intercept of the equation is attributable to an interaction between modality,
      word-length, and serial position. The results lead us to reject this possibility.
      Experiment 2 examined the shape of the span function for visual presentation of
      lists read aloud or silently. The results show that the intercept of the span
      function disappears for silent presentation but not for aloud presentation. The
      results are discussed in terms of a balance between two opposing effects of word
      length.

PMID- 15948625
TI  - Does number data entry rely on the phonological loop?
AB  - Two experiments investigated effects of articulatory processing on number data
      entry. Participants entered four-digit numbers presented as either words or
      numerals on a keyboard, either under an articulatory condition or in silence. In
      Experiment 1, the articulatory condition was articulatory suppression; in
      Experiment 2, it was vocalisation. In Experiment 1, the articulatory suppression
      group typed initial digits faster than the silent group, but for subsequent
      digits, the opposite pattern occurred at least with word stimuli. In Experiment
      2, the silent group typed initial digits faster but typed subsequent digits
      somewhat slower than the vocalisation group. Thus, articulation of numbers, which
      promotes entry into the phonological loop of working memory, retards processing
      of initial digits but enhances processing of subsequent digits.

PMID- 15948626
TI  - Is the interference between memory processing and timing specific to the use of
      verbal material?
AB  - Increasing load in a memory task performed simultaneously with a timing task
      shortens perceived time, an effect that has been observed previously with memory
      tasks using verbal material. The present experiments examine whether two similar
      memory tasks, one in which verbal material is used and another one in which
      nonverbal material is used, would produce similar interference effects on
      concurrent time reproduction. In Experiment 1, the number of nonverbal stimuli
      (pseudo-random dot patterns) was manipulated in a memory task performed while a
      temporal interval to be reproduced was encoded. Reproductions shortened
      proportionally to the duration of memory processing executed during time
      estimation. Verbal stimuli (consonants) were used in Experiment 2 in otherwise
      identical experimental conditions. Effects observed in Experiment 2 were
      comparable to those obtained in Experiment 1. Taken together, these results
      support the notion that interference from memory tasks on concurrent time
      estimation is not determined by the specific type of material processed in
      memory, but instead by the duration of memory processing.

PMID- 15948627
TI  - The relationship between short-term memory and working memory: complex span made
      simple?
AB  - This experiment addresses the question of what makes a working memory measure a
      good predictor of higher-level abilities. Verbal and visuospatial processing
      episodes were interleaved with distinct verbal and visuospatial storage episodes
      to form four complex span tasks. Although these measures were reliable predictors
      of reading and mathematics ability in children, they were no more predictive of
      these abilities than corresponding simple span tasks involving storage alone.
      However, when individual differences in storage ability and processing capacity
      were controlled for, residual variance in complex span performance was related to
      academic ability in some cases. These findings indicate that complex span tasks
      are multiply determined, and that differences in task structure can dramatically
      influence the relative importance of these multiple constraints and the
      predictive power of a complex span measure.

PMID- 15948628
TI  - Contrasting contributions of phonological short-term memory and long-term
      knowledge to vocabulary learning in a foreign language.
AB  - The contributions of phonological short-term memory and existing foreign
      vocabulary knowledge to the learning of new words in a second language were
      compared in a sample of 40 Greek children studying English at school. The
      children's speed of learning new English words in a paired-associate learning
      task was strongly influenced by their current English vocabulary, but was
      independent of phonological memory skill, indexed by nonword repetition ability.
      However, phonological memory performance was closely linked to English vocabulary
      scores. The findings suggest that in learners with considerable familiarity with
      a second language, foreign vocabulary acquisition is mediated largely by use of
      existing knowledge representations.

PMID- 15948629
TI  - Dissociating mental transformations and visuo-spatial storage in working memory:
      evidence from representational neglect.
AB  - A study is reported of visuo-spatial working memory in two individuals suffering
      from a cognitive deficit known as unilateral spatial neglect, and seven healthy
      control participants. Both patients have difficulties reporting details on the
      left side of imaged representations, and one has an additional difficulty with
      perceptual input to the left of his body midline. All participants were asked to
      report the location and identity of objects presented in novel 2 x 2 arrays that
      were either present throughout or were described orally by the experimenter, with
      no visual input. On half of the trials, the report was to be made from the
      opposite perspective, requiring 180 degree mental rotation of the mentally
      represented array. The patients show an impaired ability to report details from
      the presented or the imagined left, but had no difficulty with mental rotation.
      Results point to a clear separation between the processes of perception and those
      of visuo-spatial working memory. Results also suggest that the patients might be
      suffering from damage to the system used for holding visuo-spatial
      representations rather than a difficulty with attending to elements of that
      representation.

PMID- 15948630
TI  - Just lying there, remembering: improving recall of prose in amnesic patients with
      mild cognitive impairment by minimising interference.
AB  - The hallmark of amnesia is poor explicit long-term memory along with normal short
      term memory. It is often stated that information encountered by amnesic patients
      is forgotten within 1 minute of presentation. However, previous work has not
      distinguished between forgetting as a function of time versus the interfering
      material occupying that time. We show that there is a marked benefit of reduced
      interference in amnesic patients with mild cognitive impairment (MCI), a
      condition that is characterised by anterograde amnesia in the absence of other
      neuropsychological deficits and carries an increased risk for Alzheimer's
      disease. The result suggests that long-term memory is encoded in these patients
      to a greater extent than had been realised but that their memory is highly
      vulnerable to interference.

PMID- 15948631
TI  - Type-III effectors: sophisticated bacterial virulence factors.
AB  - Bacterial pathogens cause a wide spectrum of diseases in human and other animals.
      Some virulence factors, which are referred to as effectors, are directly
      translocated into the host cell via an injection apparatus, i.e., the type-III
      secretion system. Most effectors mimic host molecules, and translocated effectors
      are thereby able to perturb or modulate host cell signaling, cytoskeletal
      rearrangement, vesicular traffic, and autophagy, thus eliciting disease.
      Effectors are roughly classified among exotoxins, but in most cases, their
      functions are exerted focally when they are translocated into the host cell.

PMID- 15948632
TI  - A simple framework to describe the regulation of gene expression in prokaryotes.
AB  - Based on the bimolecular mass action law and the derived mass conservation laws,
      we propose a mathematical framework in order to describe the regulation of gene
      expression in prokaryotes. It is shown that the derived models have all the
      qualitative properties of the activation and inhibition regulatory mechanisms
      observed in experiments. The basic construction considers genes as templates for
      protein production, where regulation processes result from activators or
      repressors connecting to DNA binding sites. All the parameters in the models have
      a straightforward biological meaning. After describing the general properties of
      the basic mechanisms of positive and negative gene regulation, we apply this
      framework to the self-regulation of the trp operon and to the genetic switch
      involved in the regulation of the lac operon. One of the consequences of this
      approach is the existence of conserved quantities depending on the initial
      conditions that tune bifurcations of fixed points. This leads naturally to a
      simple explanation of threshold effects as observed in some experiments.

PMID- 15948633
TI  - Construction of non-symmetric substitution matrices derived from proteomes with
      biased amino acid distributions.
AB  - Automatic comparison of compositionally biased genomes, such as that of the
      malarial causative agent Plasmodium falciparum (82% adenosine + thymidine), with
      genomes of average composition, is currently limited. Indeed, popular tools such
      as BLAST require that amino acid distributions be similar in aligned sequences.
      However, the P. falciparum genome is so biased that six amino acids account for
      more than 50% of the protein composition. One reason for the comparison methods
      failure lies in the compositional difference between the query and the subject
      proteomes, which is not taken into account in the amino acid substitution
      matrices. This paper introduces a method to derive substitution matrices, in
      particular BLOSUM 62, in the frame of the information theory. It allows the
      construction of non-symmetrical matrices, taking into account the non-symmetric
      amino acid distributions. The dirAtPf family of matrices allowing the comparison
      of P. falciparum and A. thaliana is given as an example. This paper further
      provides an analysis of the obtained matrices in the frame of the information
      theory, supporting the discrimination advantage they bring.

PMID- 15948634
TI  - AFLP analysis of the genetic diversity of Meloidogyne chitwoodi and M. fallax,
      major agricultural pests.
AB  - M. chitwoodi and M. fallax populations are clustered and separated from the other
      species studied. The genetic diversity observed for M. incognita, M. arenaria, M.
      javanica, M. hapla, and M. mayaguensis correlates well with the previously
      validated species. Two main groups can be identified within the M. chitwoodi/M.
      fallax cluster, the first group comprises only M. chitwoodi populations whereas
      the second group is made of M. chitwoodi and M. fallax populations. Moreover, M.
      chitwoodi displays a higher genetic diversity than M. fallax and is characterised
      by the presence of several clusters.

PMID- 15948635
TI  - [Metabolic and endocrine effects of water and/or food deprivation in rats].
AB  - Metabolic and endocrine effects of water and/or food deprivation in rats. We aim
      at studying the effect of water deprivation, food deprivation and their
      combination for three days on adrenal cortex, pituitary-thyroid axis and
      vasopressinergic system activity in rats. Corticosterone level was determined by
      fluorimetric method. The levels of free thyroxine (FT4) and thyroid stimulating
      hormone (TSH) were determined by immunoenzymatic assay and vasopressin (AVP)
      level was determined by radio-immunoassay. In all three groups, basal levels of
      plasma corticosterone were increased. A thyroid dysfunction was shown after water
      deprivation, food deprivation and their combination reflected by a significant
      decrease in FT4 levels. Paradoxically, a significant decrease in TSH level was
      observed in food-deprived rats and in rats subjected to simultaneous food and
      water deprivation, while a slight and not significant decrease in TSH level was
      shown in water-deprived rats. A significant increase in plasma AVP level was
      observed after water deprivation and simultaneous water and food deprivation,
      while no change was found after food deprivation. The data indicated that water
      deprivation, food deprivation and their combination stimulated the adrenal
      cortex, thereby suggesting a stress state. On the other hand, it seems that
      nutritional stress modifies the pituitary-thyroid axis through mechanisms
      different from those of osmotic stress. Moreover, it seems that food deprivation
      partially prevented the stimulatory effect of water deprivation on
      vasopressinergic system.

PMID- 15948636
TI  - Clutch size: a major sex ratio determinant in fig pollinating wasps?
AB  - Under local mate competition, sex ratio theory predicts that increasing numbers
      of ovipositing females (foundresses) on a site should lead to higher proportions
      of males in their broods. Fig pollinators have confirmed this prediction. It is
      also predicted that with decreasing clutch size, solitary foundresses should
      produce increasing proportions of sons. We show this to be true. Further, when
      several females compete, brood size decreases. As a result, the proportion of
      males increases, and this could provide a mechanistic explanation of sex ratio
      response to numbers of colonizing females. Therefore, sex ratio data on fig wasps
      need to be reassessed to determine whether females 'count' other foundresses, as
      is generally accepted, or whether they simply 'count' the number of eggs that
      they lay.

PMID- 15948637
TI  - Early divergence among the Alestidae (Teleostei, Ostariophyses, Characiformes):
      mitochondrial evidences and congruence with morphological data.
AB  - The African family Alestidae (Ostariophysii: Characiformes) includes today 13
      genera, among which seven are monospecific. The size range observed in the family
      greatly varies with species ranging from 21 mm up to 130 cm for more than 50 kg.
      Among the Alestidae, three tribes were previously identified: the Alestini, the
      Hydrocinini and the Petersiini, that include all the miniaturised species.
      Previous phylogenetic studies mainly focussed on the relationships between the
      genera Alestes, Brycinus, Bryconaethiops and Hydrocynus and left the phylogenetic
      affinities of the genera from the tribe Petersiini unexplored. We assessed the
      molecular phylogenetic relationships within the family using partial
      mitochondrial ribosomal DNA sequences of the 12S and 16S genes and evaluated the
      congruence with available morphological characters by separate and combined
      analyses. We especially focussed on the phylogenetic status of the tribe
      Petersiini and further investigated the early divergence among the family. Our
      results lead to the identification of two major lineages and to the description
      of three new clades. The relationships inferred allowed us to reject monophyly of
      the genera Brycinus, Micralestes and Rhabdalestes and to suggest that the genus
      Bryconaethiops should be removed from the tribe Alestini. We also have shown that
      miniaturization occurred more than once, contrary to the predictions of the
      present classification.

PMID- 15948638
TI  - [In vivo spetrometric analysis of the electrical impedance of the first leaf of
      maize (Zea mays L.) as a function of soil and atmosphere hydrous conditions].
AB  - In vivo spectrometric analysis of the electrical impedance of the first leaf of
      maize (Zea mays L.) as a function of soil and atmosphere hydrous conditions. We
      have measured the electrical resistance and capacitance of the first leaf of
      maize aged 14 days. The plants were cultivated at different levels of soil and
      atmospheric humidity and submitted to quiet or agitated air. In 'control' plants
      cultivated in quiet air under moderate relative humidity (HRA) (50 to 60%), the
      amplitude of the spectrometric bioimpedance spectrum (CSB) increased with the
      quantity of water available to the roots. Agitated air or elevated HRA increased
      the magnitude of the CSB in plants cultivated at 40% of the maximal retention
      capacity (CRM) of the soil. On the other hand, the CSB decreased in plants
      cultivated at 60% of the CRM or in hydroponics. This was accompanied by a
      dramatic decrease in the electrical resistance. The action of the atmospheric
      factors studied depends on the quantity of water where the roots are bathing.

PMID- 15948639
TI  - Warming and exponential abundance increase of the subtropical fish Capros aper in
      the Bay of Biscay (1973-2002).
AB  - The exponential abundance increase of a sub-tropical species, boarfish (Capros
      aper), as well as the sea bottom temperature increase in the continental shelf of
      the Bay of Biscay (France) over the three last decades are reported. This species
      was rare in the seventies and is now a dominant one. This is a small bathy
      demersal, probably short-lived species with few predators (probably because of
      the presence of strong spines) and not exploited by fisheries. In the same time,
      a significant temperature increase in the bottom waters is observed during the
      breeding season of this population. The boarfish abundance increase is related to
      the warming, its ability to invade and the absence of predators as well as the
      absence of fishing.

PMID- 15948640
TI  - [Wars never end].

PMID- 15948641
TI  - Global public health experts say failure to count Iraqi casualties is
      irresponsible.

PMID- 15948642
TI  - We don't do body counts.

PMID- 15948643
TI  - [If big tobacco cries, big pharma laughs].

PMID- 15948644
TI  - [The arrival of BAT in Italy].

PMID- 15948645
TI  - [Benzene exposure in Modena: historical trend and health risk assessment].
AB  - OBJECTIVE: The present paper estimates the 1980-2000 trend in exposure to benzene
      of the population living within the urban area of Modena. An assessment of
      leukaemia risk is also presented. DESIGN: The 2000 annual means of benzene
      atmospheric concentrations in 73 sites has been derived using a procedure which
      integrated data from fixed site stations and passive samplers: on this basis, an
      annual mean for the whole urban area has been calculated. The population exposure
      trend for the period 1980-2000 has been estimated using the information on
      traffic emission changes. The expected annual number of leukaemia cases
      attributable to benzene has been calculated by using two different approaches.
      SETTING: Residents in the urban area of Modena. MAIN OUTCOME MEASURES: Annual
      incidence of leukaemia attributable to benzene. RESULTS: In 2000, the mean urban
      concentration was about 7 microg/m3 and in average the population was exposed to
      about 9 microg/m3. In the eighties, the population exposure was 5 times higher
      than the 2000 value, with a maximum of 51 microg/m3 in 1988. The leukaemia risk
      assessment procedures gave a value of about 4 x 10(-1) with the method based on
      cumulative exposure and of about 4 x 10(-2) with the method based on weighted
      exposure. DISCUSSION AND CONCLUSION: This study is one of the few examples of
      evaluation of both the trend in benzene exposure for a population and assessment
      of leukaemia risk. Uncertainties in the assessment of health impact derive from
      inconsistencies in the underlyng methods.

PMID- 15948646
TI  - [Survey about risk perception between citizens resident in a municipal at high
      risk of environmental crisis].
AB  - OBJECTIVE: This paper describes the result of a survey carried out in 2002 about
      the risk perception of the main risk factors for health and environment in an
      industrial area at high risk of environmental crisis, in order to contribute to
      risk communication programs aiming to make the population informed and conscious
      about industrial risk. DESIGN: The survey was carried out in 2002 through
      questionnaire to investigate citizens' risk perception SETTING: Municipality of
      Portoscuso, industrial district located along the South-west coast of Sardinia,
      and active in the chemical, electrochemical fusion and rolling, thermoelectric
      fields. PARTICIPANTS: The survey has been carried out, through home interviews,
      on a representative sample of the population of Portoscuso, consisting of 148
      citizens aged between 18 and 70. MAIN OUTCOME MEASURES: The results showed that
      industrial pollution is considered high by more than 80% of the sample at global
      and even more at local level showing how this represents an important worrying
      factor for the local people. CONCLUSION: This is the basis to develop an
      effective risk communication process, that involves actively all stakeholders
      (people, experts, industry and local authorities) in risk management.

PMID- 15948647
TI  - [Social inequalities in survival of people with AIDS].
AB  - OBJECTIVE: As a result of the introduction of new highly active antiretroviral
      therapy (HAART) in industrialized countries, social inequalities in survival of
      people with AIDS were observed. The aim of this study was to evaluate the
      presence of these inequalities in a cohort of persons with diagnosis of AIDS in a
      period of wider diffusion of the therapy. DESIGN AND SETTING: Longitudinal study
      of 1,368 resident of Rome, age between 18 and 59 years, diagnosed with AIDS
      between 1996 and 2000. MAIN OUTCOME MEASURES: Survival at 31.12.2002 after
      diagnosis of AIDS was analysed with respect to variables indicating socioeconomic
      status (SES) and income (IR) calculated for census tract of residence. We
      calculated hazard ratios (HR) of death using the Cox regression model and
      adjusting for gender, age, risk factor, period of diagnosis, CD4 cell count at
      diagnosis, AIDS defining disease and hospital of diagnosis. RESULTS: The analysis
      of survival has not evidenced difference of survival for different levels of SES
      and IR. For males only, there was an increase in mortality for persons of second
      level (HR=1.68; 95%CI 1.04-2.71) and fourth level (HR=1.85; 95% CI 1.15-2.96) of
      IR when compared with the first level CONCLUSION: In this study, conducted in the
      context of wider diffusion of HAART, the social differentials in survival with
      AIDS found in previous studies were not confirmed.

PMID- 15948648
TI  - [Obtaining informed consent and resorting to ethical committee in clinical and
      epidemiological research in Italy. A survey].
AB  - OBJECTIVES: To describe how informed consent (CIn) and ethical review (CEt) are
      obtained in the Italian clinical and health research. DESIGN: survey SETTING: 6
      Italian and 7 foreigner journals in the years 2001 and 2002. SAMPLE: 157 original
      or short articles, letters and case reports for which a member of an Italian
      institution was the corresponding author. MAIN OUTCOME: Mention in the text of
      CIn and CEt procedures. RESULTS: In 42% of such studies (95% CI: 35-50%),
      informed consent was obtained; in 30% (95% CI: 23-37%), ethical committee
      approval was obtained, in 27% (95% CI: 21-35%) both had been obtained. The
      probability of informed consent and ethical review varied with type of data used
      (primary or secondary source). No significant differences, however, were noted
      based on the type of study population (vulnerable or non-vulnerable), the year,
      or the country in which the article was published (Italy or elsewhere). Keywords
      search in the articles text showed that ethical aspects of the study were not
      debated. Ethical procedures were synthetically reported as a rule, yet there were
      differences in their formulation. CONCLUSIONS: The limited resorting to CIn and
      CEt procedures and the concision and variability of their description might
      depend on the plethora of the ethical, legal, editorial guidelines available for
      Italian researchers that partially overlap and partially present specific aspects
      whose interpretation is not free of niceties.

PMID- 15948649
TI  - [Air pollution and fatal and non fatal coronary events in Rome].
AB  - OBJECTIVE: To examine the relationship between air pollution and coronary events
      in Rome in the period 1998-2000, considering both out-of-hospital deaths and
      hospitalisations. DESIGN: Time-series of daily counts of out-of-hospital deaths
      and hospitalised events, implementation of Generalised Additive Models. SETTING:
      The air pollutants taken into account were PNC (Particle Number Concentration--a
      measure of ultrafine particles), PM10, CO, NO2, SO2 and O3. The association was
      studied with respect to either single days or the cumulative effect on more
      consecutive days; furthermore, effect modification by age was tested (for the age
      groups 0-64, 65-74 and 75+). PARTICIPANTS: People resident of Rome and
      died/hospitalised for coronary causes into the city in the period 1998-2000. MAIN
      OUTCOME MEASURE: Association between pollutants and out-of-hospital
      deaths/hospitalised events. Distinction between fatal events (out-of-hospital
      deaths + hospitalisations with death within 28 days of admission) and non fatal
      events (hospitalisations with survival longer than 28 days). RESULTS: Significant
      association between PNC, PM10, and CO with out-of-hospital deaths, smaller effect
      on hospitalised events. For a variation of PNC of 28000 particles per cm3
      (interquartile range of the distribution) the increase in the risk of out-of
      hospital coronary death at lag 0 was 8.1%; for hospital admissions, the risk
      increased by 4%. The association was stronger in subjects older than 65, and was
      more evident for total fatal events than for non-fatal hospitalisations.
      CONCLUSION: The study showed increased risks of coronary events associated with
      air pollution in Rome: ultrafine particles, directly generated by vehicular
      traffic, are the environmental indicator which best characterizes the health
      risk.

PMID- 15948650
TI  - [Epidemiological researh and ethical regulations: why in Italy an observational
      study can be defined a "non-interventional trial"?].

PMID- 15948651
TI  - [Studying risks of waste landfill sites on human health: updates and
      perspectives].
AB  - OBJECTIVE: Updating current reviews on epidiomiological studies on health effects
      of waste landfill sites. MATERIALS: Seven ecological studies, two health
      monitoring investigations and two environmental investigations performed between
      2000 and 2004 are discussed. RESULTS: Excesses of risk for cancer incidence,
      mortality and congenital malformations or no excesses were reported Increasing of
      low birth weight and different types of symptoms were consistently found. None or
      very poor environmental data and individual measurements of exposure were
      available in the majority of the studies. The use of biomarkers and environmental
      monitoring data to define individual exposure was suggested by some studies.
      CONCLUSIONS: The development of new and advanced environmental epidemiology
      studies on health effects of waste sites exposure is now recommended by the
      scientific community.

PMID- 15948652
TI  - [Secular trend in incidence of cancer and infectious disease: a causal
      relationship?].

PMID- 15948653
TI  - [Newborn cohort studies: shall we use the Web?].

PMID- 15948655
TI  - [How to get out of the waste emergency in the Campania Region].

PMID- 15948654
TI  - [Automatic coding of pathologic cancer variables by the search of strings of text
      in the pathology reports. The experience of the Tuscany Cancer Registry].
AB  - The present study evaluates the application of an automatic system for variables
      coding by means of strings reading in the text of the pathology reports, in the
      database of the Tuscany Cancer Registry. Incidence data for the years 2000 (n.
      6297) and 2001 (n. 6291) for subjects for whom computerised pathology reports
      were available were included. The system is based on Queries (SQL language)
      linked to Functions (Visual Basic for Applications) that work on Windows Access.
      The agreement between original data inputted by the registrars and variables
      coded by means of automatic reading has been evaluated by means of Cohen's kappa.
      The following variables were analysed: cancer site (kappa = 0.87 between "manual"
      and automatic coding, for cases incident in the year 2001), morphology
      (kappa=0.75), Berg's morphology groups (kappa=0.87), behaviour (kappa=0.70),
      grading (kappa=0.90), Gleason (kappa=0.90), focality (kappa=0.86), lateralily
      (kappa=0.36), pT (kappa=0.92), pN (kappa=0.76), pM (kappa=0.28), number of lymph
      nodes (kappa=0.69), number of positive lymph nodes (kappa=0.70), Breslow
      thickness (kappa=0.94), Clark level (kappa=0.91), Dukes (kappa=0.74). The system
      of automatic reading of strings allows to collect a very huge amount of reliable
      information and its use should be implemented by the Registries.

PMID- 15948656
TI  - Polyrigid and polyaffine transformations: a novel geometrical tool to deal with
      non-rigid deformations - application to the registration of histological slices.
AB  - We describe in this paper a novel kind of geometrical transformations, named
      polyrigid and polyaffine. These transformations efficiently code for locally
      rigid or affine deformations with a small number of intuitive parameters. They
      can describe compactly large rigid or affine movements, unlike most free-form
      deformation classes. Very flexible, this tool can be readily adapted to a large
      variety of situations, simply by tuning the number of rigid or affine components
      and the number of parameters describing their regions of influence. The
      displacement of each spatial position is defined by a continuous trajectory that
      follows a differential equation which averages the influence of each rigid or
      affine component. We show that the resulting transformations are diffeomorphisms,
      smooth with respect to their parameters. We devise a new and flexible numerical
      scheme to allow a trade-off between computational efficiency and closeness to the
      ideal diffeomorphism. Our algorithms are implemented within the Insight Toolkit,
      whose generic programming style offers rich facilities for prototyping. In this
      context, we derive an effective optimization strategy of the transformations
      which demonstrates that this new tool is highly suitable for inference. The whole
      framework is exemplified successfully with the registration of histological
      slices. This choice is challenging, because these data often present locally
      rigid deformations added during their acquisition, and can also present a loss of
      matter, which makes their registration even more difficult. Powerful and
      flexible, this new tool opens up large perspectives, in non-rigid 3D rigid
      registration as well as in shape statistics.

PMID- 15948657
TI  - A non-rigid registration approach for quantifying myocardial contraction in
      tagged MRI using generalized information measures.
AB  - We address the problem of quantitatively assessing myocardial function from
      tagged MRI sequences. We develop a two-step method comprising (i) a motion
      estimation step using a novel variational non-rigid registration technique based
      on generalized information measures, and (ii) a measurement step, yielding local
      and segmental deformation parameters over the whole myocardium. Experiments on
      healthy and pathological data demonstrate that this method delivers, within a
      reasonable computation time and in a fully unsupervised way, reliable
      measurements for normal subjects and quantitative pathology-specific information.
      Beyond cardiac MRI, this work redefines the foundations of variational non-rigid
      registration for information-theoretic similarity criteria with potential
      interest in multimodal medical imaging.

PMID- 15948658
TI  - Teaching medical image analysis with the Insight Toolkit.
AB  - We present several case studies which examine the role that the Insight Toolkit
      (ITK) played in three medical image analysis courses and several conference
      tutorials. These courses represent the first use of ITK in a teaching
      environment, and we believe that a discussion of the teaching approach in each
      case and the benefits and challenges of ITK will be useful to future medical
      image analysis course development. ITK was found to provide significant value in
      a classroom setting since it provides both working "canned" algorithms, including
      some recently developed methods that are unavailable elsewhere, as well as a
      framework for developing new techniques and applications. Several areas of
      difficulty, particularly in regards to code complexity and advanced object
      oriented design techniques, have been identified which may make the learning
      curve of ITK somewhat more complex than a language such as Matlab.

PMID- 15948659
TI  - Lagrangian frame diffeomorphic image registration: Morphometric comparison of
      human and chimpanzee cortex.
AB  - We develop a novel Lagrangian reference frame diffeomorphic image and landmark
      registration method. The algorithm uses the fixed Langrangian reference frame to
      define the map between coordinate systems, but also generates and stores the
      inverse map from the Eulerian to the Lagrangian frame. Computing both maps allows
      facile computation of both Eulerian and Langrangian quantities. We apply this
      algorithm to estimating a putative evolutionary change of coordinates between a
      population of chimpanzee and human cortices. Inter-species functional homologues
      fix the map explicitly, where they are known, while image similarities guide the
      alignment elsewhere. This map allows detailed study of the volumetric change
      between chimp and human cortex. Instead of basing the inter-species study on a
      single species atlas, we diffeomorphically connect the mean shape and intensity
      templates for each group. The human statistics then map diffeomorphically into
      the space of the chimpanzee cortex providing a comparison between species. The
      population statistics show a significant doubling of the relative prefrontal lobe
      size in humans, as compared to chimpanzees.

PMID- 15948660
TI  - Combination drug therapies for AD: progress is slow, but we must keep trying.

PMID- 15948661
TI  - Lower lip exhibits shiny, white, nonhealing lesions. Patient was heavy smoker in
      past, and has spent much time outdoors.

PMID- 15948663
TI  - Rheumatologic illnesses: treatment strategies for older adults.
AB  - Basic objectives of arthritis therapy are to reduce musculoskeletal pain, slow
      progression of disease, maintain and improve function and quality of life, and
      avoid adverse drug reactions. Both nonpharmacologic and pharmacologic approaches
      may be taken. The former include patient education, cognitive therapy, high
      intensity progressive-resistance or strength training, weight control, cold
      therapy, heat, massage, relaxation and distraction techniques. Guiding principles
      for the pharmacologic management of musculoskeletal disease in geriatric patients
      are to 'start low and go slow,' and to provide adequate pain relief. The latter
      may include the use of topicals, such as 5% lidocaine patches or capsaicin, or
      orally administered analgesics, such as acetaminophen, tramadol, nonsteroidal
      anti-inflammatory drugs (NSAIDs), and opiates. Although attractive because of the
      reduced incidence of serious gastrointestinal adverse reactions, selective COX-2
      inhibitors may have significant renal and cardiovascular toxicities, and thus
      should be used with caution in the older patient with co-morbid diseases
      affecting these organs. Intraarticular therapies with corticosteroids, or as
      viscosupplementation, may have a role in the management of osteoarthritis. For
      patients with inflammatory arthropathies, low-dose systemic steroids or disease
      modifying agents are therapeutic. When therapy fails and pain remains intolerable
      or disabling, surgical options may be considered.

PMID- 15948662
TI  - Combination drug therapy for Alzheimer's disease: what is evidence-based, and
      what is not?
AB  - Although FDA-approved Alzheimer's disease (AD) treatment strategies
      (cholinesterase inhibitors and memantine) offer proven benefits, providers
      recognize unmet needs beyond what is currently available. Consequently there is a
      significant use of anecdotal yet unproven combinations for treating AD in
      practice. Based on the best evidence, combination drug therapy is the standard of
      care for treating other medical conditions such as malignancies, human
      immunodeficiency virus (HIV), and hypertension. We review recent combination drug
      therapy studies in AD. To date, the best evidence-based combination strategy is
      for moderate-to-severe AD, in which the addition of memantine to stable donepezil
      therapy was found to benefit cognition, behavior, and function. In milder stages
      of AD, the benefit of combination drug therapy has not been demonstrated. This
      review highlights the urgent need to systematically test additional rational drug
      combinations and the need for future trials to enroll adequate sample sizes and
      utilize relevant and sensitive outcome measures.

PMID- 15948664
TI  - Paradigm shift in NMDA receptor drug development.
AB  - Low-affinity, uncompetitive antagonists with rapid 'off-rates', such as memantine
      offer protection from dementia and other neurological disorders, but break all
      the old rules of screening for new drugs by high-affinity binding.

PMID- 15948665
TI  - B cells as a therapeutic target in autoimmune diseases.
AB  - Historically, the pathogenic role of B cells in autoimmune disease has been
      attributed to the formation of autoantibodies which, as soluble immunoglobulins
      or immunocomplexes, can trigger cellular damage and initiate the inflammatory
      cascade. Recent results from clinical trials applying B cell-directed
      therapeutics in rheumatoid arthritis and systemic lupus erythematosus have
      challenged such traditional views and encouraged novel ideas about the disease
      involvement of B cells. Suppression of disease activity, often disconnected from
      effects on autoantibody titers, has supported the notion that B cells may promote
      autoimmune disease by serving as antigen-presenting cells that sustain T cell
      activation. Likewise, B cells have been implicated in supporting the process of
      ectopic lymphoid neogenesis, a mechanism that stabilises pathogenic immune
      responses in target tissues and thus contributes to disease chronicity. As a
      general rule, clinical effects of B cell-directed therapeutics have often been
      unanticipated and unpredicted by experimental models, emphasis-ing the need to
      explore and verify disease principles in the patient.

PMID- 15948666
TI  - Inhibition of GSK-3beta as a target for cardioprotection: the importance of
      timing, location, duration and degree of inhibition.
AB  - Cardiovascular disease is the major cause of morbidity and mortality in western
      countries such as the US. Myocardial infarction leads to loss of myocytes and
      with extremely limited ability to replenish cardiomyocytes, the heart exhibits
      depressed contractility. This ultimately results in hypertrophy of the remaining
      viable myocytes, which is the primary predictor for heart failure. Thus, drug
      therapies which can reduce myocyte cell death and reduce postischaemic
      dysfunction would be expected to greatly reduce cardiac hypertrophy and
      subsequent heart failure and death. Inhibition of glycogen synthase kinase (GSK)
      3beta has been proposed as a strategy to improve postischaemic cardiomyocyte
      survival, as inhibition of GSK-3beta has been shown to reduce myocardial cell
      death following ischaemia and reperfusion. Therapies for inhibiting GSK are
      feasible as there are a number of newly developed specific inhibitors of GSK
      available, although most of these drugs have not been tested in long-term animal
      studies.

PMID- 15948667
TI  - Telomerase: a potential therapeutic target for cancer.
AB  - Telomeres are complex structures which serve to protect chromosome ends. Telomere
      shortening occurs in normal somatic cells reaching a point in which cells
      senesce. Senescence can be counteracted by activating telomerase. Telomerase
      activity is present in a majority of cancer cells and requires the upregulation
      of the reverse transcriptase component called hTERT. Because telomerase activity
      is essential for proliferation of most cancer cells, therapeutic strategies have
      been developed to inhibit its activity. These strategies centre on targeting the
      active site, hTERT and hTERC expression, core enzyme stability and telomeric DNA.
      Successful approaches involve a combination of traditional drugs with telomerase
      inhibitors. Disrupting the functional expression of hTERT is particularly
      effective in agreement with evidence that hTERT is an antiapoptotic factor in
      some cancer cells. In addition, approaches that stabilise DNA secondary
      structures may disrupt telomere maintenance through a variety of routes making
      them, potentially, very potent in attack-ing cancer cells.

PMID- 15948668
TI  - Effects of anticancer drugs on transcription factor-DNA interactions.
AB  - DNA-interacting anticancer drugs are able to affect the propensity of DNA to
      interact with proteins through either reversible binding or covalent bond
      formation. The effect of the drugs on transcription factor interactions with DNA
      is reviewed. These effects can be classified as (i) competition between a drug
      and regulatory protein for target sequences; (ii) weakening of this interaction;
      (iii) enhancement of this interaction by chemical modification of the DNA and the
      creation of non-natural binding sites; and (iv) a 'suicide' mechanism, which is
      observed when a transcription factor induces changes in DNA structure, allowing a
      drug to bind to a target sequence. Several new strategies -- the antigene
      approach with oligonucleotides, peptide nucleic acids or locked nucleic acids,
      and sequence-specific polyamides -- are also reviewed.

PMID- 15948669
TI  - ED-B fibronectin as a target for antibody-based cancer treatments.
AB  - Chemotherapeutic agents for the treatment of solid cancers do not discriminate
      between malignant and normal tissue, but rather depend on the increased
      proliferation of tumour cells versus benign cells. To reach therapeutically
      active concentrations in the tumour, large doses of these rather unspecific
      compounds have to be given to the patient, often resulting in severe side
      effects. Therefore, the goal of modern cancer research is the development of
      highly selective compounds which are able to discriminate between tumour tissue
      and normal tissue. One promising approach in this direction is antibody-mediated
      targeted cancer therapy which may either block an important receptor-ligand
      interaction or deliver a therapeutically active molecule to an otherwise
      nonfunctional target. A prerequisite for such an approach is the tumour-selective
      expression of the respective target structure. This review discusses extra domain
      B fibronectin as a promising target which is associated with tumour angiogenesis
      and tumour growth for the development of novel antibody-mediated therapies.

PMID- 15948670
TI  - Targeted therapy for epithelial ovarian cancer.
AB  - Ovarian cancer is the leading cause of death in women with gynecological
      malignancies and overall survival for patients with advanced epithelial ovarian
      cancer (EOC) remains poor. The majority of patients recur after initial
      treatment. A strategy for improving outcome is to minimise recurrence via
      targeted therapy in patients after front-line therapy, or more appropriately as
      consolidation therapy. EOC represents an attractive target because of the biology
      of the disease and that the bulk of disease occurs in the peritoneal cavity. To
      initiate targeted therapy, a candidate target must be identified. Innovative
      approaches via targeted therapy to control metastatic residual EOC are currently
      under investigation. The targets are molecules and pathways, on which cancer
      cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential
      targeted therapies include: proapoptototic therapy, suicide gene therapy, signal
      transduction, antiangiogenesis, immunotherapy and cytokine therapy. The
      utilisation of these targets in the clinic demands carefully conducted, well
      coordinated but discovery-oriented translational research in the form of clinical
      trials that can quickly assess alternative strategies or combination of
      strategies that could result in clinical benefit. Therefore, targeted therapy for
      epithelial ovarian cancer, especially after complete response to standard
      regimens, represents a paradigm whose time has come to be nurtured.

PMID- 15948671
TI  - Anaplastic lymphoma kinase and its signalling molecules as novel targets in
      lymphoma therapy.
AB  - A crucial issue in the development of molecularly-targeted anticancer therapies
      is the identification of appropriate molecules whose targeting would result in
      tumour regression with a minimal level of systemic toxicity. Anaplastic lymphoma
      kinase (ALK) is a transmembrane receptor tyrosine kinase, normally expressed at
      low levels in the nervous system. As a consequence of chromosomal translocations
      involving the alk gene (2p23), ALK is also aberrantly expressed and
      constitutively activated in approximately 60% of CD30+ anaplastic large cell
      lymphomas (ALCLs). Due to the selective overexpression of ALK in tumour cells,
      its direct involvement in the process of malignant transformation and its
      frequent expression in ALCL patients, the authors recognise ALK as a suitable
      candidate for the development of molecularly targeted strategies for the
      therapeutic treatment of ALK-positive lymphomas. Strategies targeting ALK
      directly or indirectly via the inhibition of the protein networks responsible for
      ALK oncogenic signalling are discussed.

PMID- 15948672
TI  - Therapeutic targeting of receptor tyrosine kinases in lung cancer.
AB  - Lung cancer is a difficult illness with a poor overall survival. Even though
      combination strategies with chemotherapy, radiation therapy and surgery have all
      been utilised, the overall outcome for this disease continues to be relatively
      disappointing. In order to make a difference in the treatment of lung cancer,
      novel therapeutics will have to be developed. Through basic biological studies, a
      number of receptor tyrosine kinases have been implicated in the pathogenesis and
      progression of lung cancer. In this review, the authors summarise the mechanisms
      of several major receptor tyrosine kinases in lung cancer, especially epidermal
      growth factor receptor, Her2/neu, MET, vascular endothelial growth factor and
      KIT. The biology associated with these receptors is described, and the various
      novel therapeutic inhibitory strategies that are ongoing in preclinical and
      clinical studies for lung cancer are detailed. Through understanding of receptor
      tyrosine kinases and the utilisation of specific inhibitors, it is hopeful that a
      dramatic impact will be made on the biology and therapy for lung cancer.

PMID- 15948673
TI  - Targeting novel antigens for prostate cancer treatment: focus on prostate
      specific membrane antigen.
AB  - Prostate-specific membrane antigen (PSMA) is a relatively omnipresent, but unique
      Type II dimeric transmembrane protein with a multiplicity of functions and has
      been shown to be a reasonable target for immunological approaches such as
      vaccines or more directed therapy with radioactively labelled monoclonal
      antibodies against PSMA. Given the abundance of various glycoprotein and
      carbohydrate antigens expressed on the surface of prostate cancer cells and cell
      lines, PSMA stands out as another 'self' antigen which is not only expressed on
      cancer cells, but on neovasculature. Although vaccines are varied in their design
      and target goal, recent technology has afforded researchers the opportunity to
      induce recruitment of multiple effector cell populations, cytokines and factors
      which can elicit both cellular and humoral responses. This review serves to
      present unique approaches in vaccine development which can induce immunological
      responsiveness with potential impact on disease progression and to introduce PSMA
      as a potential target for multimodality therapies.

PMID- 15948674
TI  - Kv1.3 potassium channel blockade as an approach to insulin resistance.
AB  - Diabetes mellitus is a devastating metabolic disease caused by either insulin
      deficiency or resistance and characterised by abnormal glucose, protein and lipid
      metabolism. It affects > 150 million people worldwide, 14 million in the US alone
      (90% Type II and 10% Type I) where it accounts for approximately 15% of
      healthcare expenditure. Insulin resistance is a cardinal feature of Type II
      diabetes. The molecular mechanisms that mediate insulin resistance are under
      intense scrutiny, and a major goal of this effort is to uncover potential
      therapeutic targets. Recent data indicate that the voltage-gated potassium
      channel, Kv1.3, is an important regulator of peripheral insulin sensitivity and
      glucose metabolism. Indeed, Kv1.3 channel inhibition increases insulin
      sensitivity by decreasing inflammatory cytokines and by facilitating the
      translocation of GLUT4 to the plasma membrane. In light of these novel findings,
      the author believes that Kv1.3 is a promising target for the development of drugs
      useful in the management of insulin resistance and diabetes.

PMID- 15948675
TI  - The JNK pathway as a therapeutic target for diabetes.
AB  - The hallmark of Type 2 diabetes is insulin resistance and pancreatic beta-cell
      dysfunction. Under diabetic conditions, the c-jun N-terminal kinase (JNK) pathway
      is activated in various tissues, which is involved in both insulin resistance and
      beta-cell dysfunction. Activation of the JNK pathway interferes with insulin
      action and reduces insulin biosynthesis, and suppression of the JNK pathway in
      diabetic mice improves insulin resistance and beta-cell function, leading to
      amelioration of glucose tolerance. Taken together, the JNK pathway is likely to
      play a central role in the progression of insulin resistance and beta-cell
      dysfunction and, thus, could be a potential therapeutic target for diabetes.

PMID- 15948676
TI  - Glucagon as a target for the treatment of Type 2 diabetes.
AB  - Glucagon is the key counter-regulatory hormone that opposes the action of
      insulin. In states of relative hypoglycaemia, glucagon acts to increase blood
      glucose by stimulating hepatic glycogen breakdown and gluconeogenesis to achieve
      euglycaemia. Type 2 diabetes is characterised by inappropriate regulation of
      hepatic glucose production, which is due, at least in part, to an imbalance in
      the bihormonal relationship between plasma levels of glucagon and insulin. The
      glucose-lowering effects of glucagon peptide antagonists and antiglucagon
      neutralising antibodies first demonstrated the potential of glucagon receptor
      (GCGR) antagonism as a treatment for hyperglycaemia. In recent years, the
      development of GCGR antisense oligonucleotides and small molecular weight GCGR
      antagonists have been pursued as possible therapeutic agents to target glucagon
      action as a treatment for Type 2 diabetes.

PMID- 15948677
TI  - The promise of cytokine antibody arrays in the drug discovery process.
AB  - The introduction of cytokine antibody arrays has added a new approach for
      investigators to simultaneously measure multiple cytokine levels in biological
      samples. Several different platforms have been developed. The ability to measure
      hundreds of cytokine levels with high specificity and sensitivity within a very
      limited amount of samples is a powerful tool. Many investigators worldwide have
      applied this novel technology in their biomedical research, particularly in drug
      discovery. Undoubtedly, the technology will continue to be improved and the
      application increased in the next several years.

PMID- 15948678
TI  - Oestrogen functions in skin and skin appendages.
AB  - Oestrogens have significant effects on different cell types important in skin
      physiology, including the epidermal keratinocytes, dermal fibroblasts and
      melanocytes. In addition, they can also modulate skin appendages such as the hair
      follicle, the sebaceous gland and the apocrine glands. Oestrogens may also have
      important modulatory roles in events such as skin ageing, pigmentation, hair
      growth, sebum production and skin cancer. It is now recognised that oestrogens
      can modulate their actions via two distinct intracellular receptors (ERalpha and
      ERbeta) or via cell surface receptors, which activate specific second messenger
      signalling pathways. This paper highlights the effects of oestrogens on different
      components of the skin and reviews some of the more recent developments in terms
      of receptor expression and cell signalling pathways.

PMID- 15948679
TI  - Pathologic tooth migration.
AB  - Pathologic tooth migration (PTM) is a common complication of moderate to severe
      periodontitis and is often the motivation for patients to seek periodontal
      therapy. In this review of the literature, available information concerning
      prevalence, etiology, treatment, and prevention of pathologic tooth migration is
      summarized. Prevalence of PTM among periodontal patients has been reported to
      range from 30.03% to 55.8%. A survey of the literature regarding chief complaints
      of periodontal patients support these high prevalence findings. The etiology of
      PTM appears to be multifactorial. Periodontal bone loss appears to be a major
      factor in the etiology of PTM. Many aspects of occlusion can contribute to
      abnormal migration of teeth, and more than one of those factors may be present in
      an individual patient. Soft tissue forces of the tongue, cheeks, and lips are
      known to cause tooth movement and in some situations can cause PTM. Also
      considered important in the etiology of PTM is pressure produced from
      inflammatory tissues within periodontal pockets. Because extrusion is a common
      form of PTM, clinical observations support the theory that eruption forces
      sometimes play a role in the etiology of PTM. Many oral habits have been
      associated with PTM which are often difficult for the therapist to detect. Most
      cases of severe PTM require a team approach to achieve success. Periodontal,
      orthodontic, and prosthodontic treatment are often required. Many patient
      variables enter into the selection of treatment for PTM. In early stages of PTM,
      spontaneous correction of migrated teeth sometimes occurs after periodontal
      therapy. Light intrusive forces are used successfully to treat extrusion and
      flaring forms of PTM. Based on the literature reviewed, it appears that many
      cases of PTM could be prevented through the early diagnosis and treatment of
      periodontal disease, occlusal contributing factors, gingival enlargement, and
      oral habits.

PMID- 15948680
TI  - Evaluation of the safety and efficacy of periodontal applications of a living
      tissue-engineered human fibroblast-derived dermal substitute. I. Comparison to
      the gingival autograft: a randomized controlled pilot study.
AB  - BACKGROUND: Periodontists have found the gingival autograft to be an effective
      and predictable technique to increase the amount of attached gingiva around
      teeth, but this technique requires the surgeon to harvest donor tissue from a
      remote surgical site. The present study seeks to evaluate the safety and
      effectiveness of a tissue-engineered skin equivalent, a living human fibroblast
      derived dermal substitute (HF-DDS), compared to a gingival autograft (GA)
      consisting of donor tissue harvested from the patient's palate in a procedure
      designed to increase the amount of keratinized tissue around teeth that do not
      require root coverage. METHODS: Twenty-five patients with insufficient attached
      gingiva associated with at least two teeth in contralateral quadrants of the same
      jaw were treated. One tooth in each patient was randomized to receive either a GA
      (control) or a HF-DDS graft (test). Clinical parameters measured at baseline and
      3, 5, 7, 9, and 12 months included recession, clinical attachment level,
      keratinized tissue height, and plaque index. Probing depth was measured at 7, 9,
      and 12 months. Inflammation of each site was scored and texture and color of the
      grafted tissue were compared to the surrounding tissue. Resistance to muscle pull
      was evaluated and a questionnaire was used to determine patient preference.
      Surgical position of the graft and alveolar bone level were recorded at the
      surgical visit and patients were evaluated weekly for the first 4 weeks at which
      time recession and level of oral hygiene were measured. Biopsies and persistence
      studies were performed on a subset of the patients. RESULTS: Results for both
      test and control groups were similar for all measured clinical parameters with
      the exception of amount of keratinized tissue and percent shrinkage of
      keratinized tissue. The control group exhibited an average of 1.0 to 1.2 mm more
      keratinized tissue over time than the test group (P <0.001) and the control group
      had about half as much shrinkage as the test group over time (P <0.001). Test
      sites demonstrated significantly better color match over time compared to control
      sites. Similarly, tissue texture for test sites was significantly better than
      control sites over time. CONCLUSIONS: Based on the results of this investigation,
      the tissue engineered HF-DDS graft was safe and capable of generating keratinized
      tissue without the morbidity and potential clinical difficulties associated with
      donor site surgery. The GA generated more keratinized tissue and shrank less than
      the HF-DDS graft, but the test graft generated tissue that appeared more natural.

PMID- 15948681
TI  - Evaluation of the safety and efficacy of periodontal applications of a living
      tissue-engineered human fibroblast-derived dermal substitute. II. Comparison to
      the subepithelial connective tissue graft: a randomized controlled feasibility
      study.
AB  - BACKGROUND: The subepithelial connective tissue graft, traditionally harvested
      from the patient's palate, is commonly used for root coverage in periodontal
      recession defects. This study evaluates the safety and effectiveness of a living
      human fibroblast-derived dermal substitute (HF-DDS) compared to a connective
      tissue graft (CTG) for root coverage in these situations. METHODS: Thirteen
      patients were selected for this study. Each patient had Miller Class I or II
      bilateral facial recession defects > or =3 mm on two non-adjacent teeth. The test
      tooth received an HF-DDS graft, while a CTG was placed on the control site. The
      10 test surgeries were performed by one operator and three pilot surgeries were
      performed by another surgeon. Eight of the HF-DDS sites received a single
      thickness of material; five received a double thickness. Clinical measurements
      were taken at baseline; 1 week; and 1, 3, and 6 months following surgery.
      Parameters measured were plaque index, recession depth, clinical attachment
      levels, recession width, probing depth, and width of keratinized tissue. All
      clinical readings were taken by a masked, calibrated examiner. RESULTS: There
      were no statistically significant differences between the test and control
      groups. The amount of root coverage was slightly greater for the control group
      than for the test group, but statistically the difference was insignificant. The
      width of the recession defect measured at the cemento-enamel junction (CEJ) for
      the test group was slightly smaller than that of the control group at the
      conclusion of the study. The amount of keratinized tissue was the same in both
      groups at 6 months. The probing depth was slightly greater in the control group
      as was the gain in clinical attachment, but neither was statistically
      significant. The amount of root coverage obtained when one layer of HF-DDS was
      used compared to the amount of coverage obtained when two layers were used
      approached statistical significance, but the small sample size may have been
      responsible for the difference. CONCLUSION: Within the limits of this study, the
      human fibroblast-derived dermal substitute may offer potential as a substitute to
      the connective tissue graft for covering areas of facial Miller Class I or Class
      II gingival recession in humans.

PMID- 15948682
TI  - Platelet-rich plasma combined with a porous hydroxyapatite graft for the
      treatment of intrabony periodontal defects in humans: a comparative controlled
      clinical study.
AB  - BACKGROUND: The aim of the present controlled clinical study was to compare
      platelet-rich plasma (PRP) combined with a biodegradable ceramic, porous
      hydroxyapatite (HA) with a mixture of HA and saline in the treatment of human
      intrabony defects. METHODS: Seventy interproximal intrabony osseous defects in 70
      healthy, non-smoking subjects diagnosed with chronic periodontitis were included
      in this study. Thirty-five subjects each were randomly assigned to either the
      test group (PRP and HA) or control group (HA with saline). Clinical and
      radiographic measurements were determined at baseline and the 12-month
      evaluation. RESULTS: When compared to baseline, the 12-month results indicated
      that, while both treatment modalities resulted in significant changes in all
      clinical parameters (gingival index, bleeding on probing, probing depth, clinical
      attachment level, and intrabony defect fill; P <0.001), the test group exhibited
      statistically significant changes compared to the control sites in probing depth
      reduction: 4.7 +/- 1.6 mm versus 3.7 +/- 2.0 mm (P <0.05); clinical attachment
      gain: 3.4 +/- 1.7 mm versus 2.0 +/- 1.2 mm (P <0.001); and vertical relative
      attachment gain: 70.3% +/- 23.4% versus 45.5% +/- 29.4% (P <0.001). CONCLUSION:
      Treatment with a combination of PRP and HA compared to HA with saline led to a
      significantly more favorable clinical improvement in intrabony periodontal
      defects.

PMID- 15948683
TI  - The influence of anatomical features on the outcome of gingival recessions
      treated with coronally advanced flap and enamel matrix derivative: a 1-year
      prospective study.
AB  - BACKGROUND: Coronally advanced flap (CAF) is one of the most effective treatments
      of Miller Class I and II recessions. Even if excellent outcomes are reported in
      the literature, complete root coverage is not always predictable, since many
      surgical and host-related factors may affect the percentage of root coverage
      obtained. The aim of this clinical study was to evaluate if some anatomical
      features such as tissue thickness, papillae height and width, recession depth,
      and vestibular bone height may influence defect coverage of Miller Class I and II
      gingival recessions treated with CAF in combination with enamel matrix derivative
      (EMD). METHODS: Thirty healthy, non-smoking patients (13 men and 17 women; mean
      age 32.8 +/- 6.2 years) were enrolled. Each patient was treated for one single
      recession using a CAF with the adjunct of EMD. Clinical parameters at baseline
      and 6 and 12 months were recorded and compared by using paired Student t test.
      Data were subdivided in two groups according to the baseline recession depth
      (REC): REC < 4 mm (group 1) and REC > or = 4 mm (group 2). The relation between
      the anatomical parameters (papilla height, papilla width, crestal bone height,
      and flap thickness) and percent of root coverage was evaluated by multiple linear
      regression analysis. RESULTS: At 12 months, 91.7% of root coverage was obtained
      with a mean attachment gain of 3.23 mm. Better results in terms of percentage of
      root coverage were obtained when the baseline REC was < 4 mm compared to defects
      > or = 4 mm (96.5% versus 83.5%). Flap thickness was positively correlated to the
      percentage of root coverage. For gingival recessions > or = 4 mm, 100% root
      coverage was achieved only when tissue thickness was > or = 1 mm. Root coverage
      percentage was slightly related to papilla width in both groups, while it was
      associated with papilla height only in group 1 (P = 0.004). Only in patients in
      group 1 was the height of bone on the vestibular side related to the percentage
      of root coverage obtained (P = 0.003). CONCLUSIONS: The results of the present
      study suggest that baseline recession depth and flap thickness may influence the
      outcome of marginal tissue recession therapy with CAF plus EMD at 12 months.
      There is not a clear relation between root coverage and other anatomical features
      as papilla width, papilla height, and the amount of bone on the vestibular side.

PMID- 15948684
TI  - Healing of dehiscence defects following root surface demineralization with
      tetracycline: a histologic study in monkeys.
AB  - BACKGROUND: The purpose of this study was to histologically evaluate the healing
      of experimental dehiscence defects after surface demineralization with
      tetracycline hydrochloride. METHODS: Six adult male monkeys (Cebus apella) were
      used in this study. Dehiscence defects were surgically created on the buccal
      aspect of the mandibular lateral incisors in all animals. The root surfaces were
      debrided and planed. In a split-mouth design, a 10% tetracycline hydrochloride
      solution was applied to one tooth for 4 minutes (T group), followed by irrigation
      with saline. The contralateral tooth served as a control (C group). The flaps
      were repositioned and sutured. The animals were sacrificed at 6 months
      postoperatively and histological sections were processed. Computer-assisted
      histomorphometric analysis was used to evaluate the formation of new cementum,
      new bone, new connective tissue attachment, and length of the epithelium
      (junctional and sulcular). RESULTS: Bone regeneration was similar in both groups
      (1.5 +/- 0.3 mm for the T group and 1.5 +/- 0.6 mm for the C group). The C group
      showed more new cementum than the T group (2.3 +/- 0.3 mm versus 2.2 +/- 0.3 mm)
      as well as a longer epithelium (1.0 +/- 0.3 mm versus 0.9 +/- 0.2 mm). The T
      group presented more new connective tissue attachment (3.1 +/- 0.2 mm) than the C
      group (2.9 +/- 0.6 mm). However, no statistically significant differences were
      detected between the two groups. CONCLUSIONS: The amount of new attachment was
      similar in both groups. Root conditioning with 10% tetracycline solution did not
      produce any additional new attachment in comparison to the controls.

PMID- 15948685
TI  - Association of T CD4 lymphocyte levels and chronic periodontitis in HIV-infected
      brazilian patients undergoing highly active anti-retroviral therapy: clinical
      results.
AB  - BACKGROUND: Controversial data regarding the association between
      immunosuppression and prevalence/ severity of periodontal diseases in HIV
      infection have been reported. Thus, the aim of this study was to test the
      hypothesis that lower T CD4 lymphocyte levels are not related to a higher
      prevalence of chronic periodontitis in HIV-infected Brazilians undergoing highly
      active anti-retroviral therapy (HAART). METHODS: Sixty-four HIV-infected patients
      under HAART were classified as having chronic periodontitis; i.e., > or = three
      sites with probing depth (PD) and/or clinical attachment level (CAL) > or = 5 mm
      or periodontal healthy (no sites with PD > 3 mm and/or CAL > 4 mm). All subjects
      received conventional periodontal therapy. Bleeding on probing, plaque
      accumulation, PD, and CAL were registered at six sites/tooth at baseline and 4
      months after therapy. Epidemiological features and levels of T CD4 lymphocytes
      were obtained from medical records. Significance of differences in periodontal
      clinical parameters within and between groups were determined using Wilcoxon
      signed-rank and Mann-Whitney or independent sample t tests. Associations between
      T CD4 levels and clinical parameters were determined using the chi square test.
      RESULTS: Sixty-one percent of the HIV-infected patients represented AIDS cases,
      although 69% of them were periodontally healthy. The overall T CD4 lymphocyte
      mean levels was 333 +/- 254 cells/mm3 and viral load was 12,815 +/- 24,607
      copies/mm3. Yet the prevalence of chronic periodontitis was relatively low (36%).
      In addition, patients with periodontitis presented a moderate disease (mean PD =
      2.2 +/- 0.10; mean CAL = 2.6 +/- 0.13) and responded successfully to periodontal
      therapy. These subjects showed higher levels of T CD4 cells, but lower counts of
      neutrophils than periodontally healthy patients. Among periodontally healthy and
      chronic periodontitis patients, 41.7% and 22.9%, respectively, had low levels of
      T CD4 lymphocytes. No significant differences between periodontal status and
      epidemiological and immunological parameters were observed. CONCLUSION: Based on
      these results, the hypothesis that lower T CD4 lymphocyte levels are not
      associated with higher prevalence of chronic periodontitis in HIV-infected
      Brazilians under HAART cannot be rejected.

PMID- 15948686
TI  - Determination of smoking and obesity as periodontitis risks using the
      classification and regression tree method.
AB  - BACKGROUND: A model that focuses on personal risk factors associated with poor
      lifestyle has been proposed for the etiology of generalized periodontitis.
      Numerous investigations have linked individual lifestyle-related factors to
      periodontitis risk; however, a definite relationship among lifestyle-related
      factors remains unclear. The objective of this study was to determine which
      lifestyle-related factors demonstrated the greater impact on periodontitis risk.
      METHODS: The association of lifestyle-related factors, such as smoking status and
      obesity, with periodontitis was assessed in 372 Japanese workers via a self
      administered questionnaire. Smoking status and obesity were evaluated in terms of
      pack-years and body mass index (BMI), respectively. Clinical periodontal
      examination included probing depth (PD). The effective impact on periodontitis
      risk was analyzed by the classification and regression tree (CART) method and
      multiple logistic regression analysis. RESULTS: Simple logistic regression
      analyses revealed that factors such as age, gender, alcohol consumption, smoking
      status, BMI, and frequency of toothbrushing were associated with periodontitis.
      CART results demonstrated a significant correlation between periodontitis and
      pack-years, BMI, and age; in contrast, alcohol consumption, gender, and
      toothbrushing frequency were not correlated with periodontitis. The strongest
      factor for periodontitis risk was pack-years of smoking. Additionally, both pack
      years and BMI exhibited clear dose-response relationships with periodontitis.
      These relationships were maintained despite adjustment for known confounding
      factors. CONCLUSIONS: Smoking displays the greatest impact on periodontitis among
      lifestyle-related factors. Both smoking and obesity are independent risk
      indicators for periodontitis; moreover, these parameters exhibit a dose-response
      relationship with respect to periodontitis risk.

PMID- 15948687
TI  - Cyclooxygenase-2-dependent prostaglandin (PG) E2 downregulates matrix
      metalloproteinase-3 production via EP2/EP4 subtypes of PGE2 receptors in human
      periodontal ligament cells stimulated with interleukin-1alpha.
AB  - BACKGROUND: Prostaglandin E2 (PGE2), which exerts its actions via EP receptors
      (EP1, EP2, EP3, and EP4), is a bioactive metabolite produced by cyclooxygenase
      (COX)-1 and/or COX-2 from arachidonic acid. In the present study, we investigated
      whether COX-2-derived PGE2 regulated matrix metalloproteinase (MMP)-3 production
      in human periodontal ligament (PDL) cells stimulated with interleukin (IL)-1alpha
      and which EP receptors were involved in PGE2 regulation of IL-1alpha-induced MMP
      3 production. METHODS: Human PDL cells obtained from periodontally healthy
      subjects were stimulated with vehicle or IL-1alpha in the presence or absence of
      indomethacin (a COX-1/COX-2 inhibitor), NS-398 (a specific COX- 2 inhibitor),
      PGE2, EP receptor agonists, dibutyryl cAMP, and forskolin. PGE2 levels were
      assayed by enzyme-linked immunosorbent assay (ELISA). MMP-3 levels and
      caseinolytic activities were evaluated by ELISA and casein zymography,
      respectively. RESULTS: IL-1alpha enhanced both MMP-3 and PGE2 production.
      Indomethacin and NS-398 enhanced IL-1alpha-induced MMP-3 production in PDL cells,
      to the same extent, although both the agents completely inhibited IL-1alpha
      induced PGE2 production. Exogenous PGE2 reduced IL-1alpha-induced MMP-3
      production in a dose-dependent manner. Butaprost, a selective EP2 agonist, and
      ONO-AE1-329, a selective EP4 agonist, significantly inhibited IL-1alpha-induced
      MMP-3 production, although butaprost was less potent than ONO-AE-1-329. Dibutyryl
      cAMP, a cAMP analog, and forskolin, an adenylate cyclase activator, significantly
      inhibited IL-1alpha-stimulated MMP-3 production in PDL cells. CONCLUSIONS: These
      data suggest that COX-2-dependent PGE2 downregulates IL-1alpha-elicited MMP-3
      production by cAMP-dependent pathways via EP2/EP4 receptors in human PDL cells.
      cAMP-elevating agents such as EP2/EP4 receptor activators may regulate the
      destruction of extracellular matrix components in periodontal tissue.

PMID- 15948688
TI  - Effect of cyclosporin A on the mineral apposition rate of cementum and dentin in
      growing rats.
AB  - BACKGROUND: Since there is no direct information to verify whether cyclosporin A
      (CsA) can affect the mineralization of dental hard tissue, the formation of
      dentin and cementum in growing rats was recorded by labeling the mineral phase of
      these tissues with fluorochrome marker in this study. METHODS: After the
      extraction of the right maxillary molars, 30 male 3-week-old Sprague-Dawley rats
      were assigned to two groups. Following a 2-week healing period, the experimental
      rats received 30 mg/kg CsA daily for 7 weeks, while the control rats received
      only mineral oil. The fluorescent markers, calcein and alizarin red, were given
      on alternate weeks for 7 weeks. At the end of study, the mandibles were obtained
      and undemineralized sections were processed. Serial sections, 8 microm thick,
      were cut for the entire distal roots of the first molars. Five central sections
      were selected to determine the mineral apposition of cellular cementum and dentin
      at the apex and middle of root, respectively. RESULTS: The apposition rates of
      apical cellular cementum were significantly influenced by CsA therapy, occlusal
      function, and observation duration. However, the dentin apposition rates were
      significantly influenced by the observation intervals only. CONCLUSIONS: In this
      study, CsA therapy and occlusal function significantly influenced the apposition
      rates of apical cementum, but not the rates of mid-root dentin. Our hypothesis
      that CsA can induce oral hard tissue alterations, as well as gingival overgrowth,
      is demonstrated.

PMID- 15948689
TI  - Impaired degradation of matrix collagen in human gingival fibroblasts by the
      antiepileptic drug phenytoin.
AB  - BACKGROUND: Gingival overgrowth (GO) is a serious adverse effect associated with
      the administration of phenytoin (PHT), with PHT-induced GO characterized by a
      massive accumulation of extracellular matrix components, especially collagen, in
      gingival connective tissues. However, the etiology of such collagen accumulation
      is still largely unknown. We examined the effects of PHT on the collagen
      degradation process leading to collagen accumulation in human gingival
      fibroblasts (HGF). METHODS: HGFs were cultured with various concentrations of PHT
      and viable cell numbers and collagen amounts were determined. Gene and protein
      expressions of matrix metalloproteinases (MMP) and tissue inhibitors of MMPs
      (TIMP) were quantified with reverse transcription-polymerase chain reaction (RT
      PCR) analyses and Western blotting, respectively. Cellular endocytosis of
      collagen was assayed using flow-cytometric analysis. The effects of PHT on
      extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibitor kappaB-alpha
      (IkappaB-alpha) were assayed. RESULTS: The proliferation of HGFs was not affected
      by PHT, whereas it significantly increased collagen accumulation. Further, the
      expressions of MMP-1, -2, and -3 were markedly suppressed by PHT, whereas that of
      TIMP-1 was induced in a dose- and time-dependent manner. PHT also markedly
      prevented collagen endocytosis by HGFs, which was associated with the suppression
      of alpha2beta1-integrin expression. In addition, the phosphorylation of ERK1/2
      and IkappaB-alpha degradation were suppressed by PHT. CONCLUSIONS: These results
      suggest that PHT causes an impaired degradation of collagen by suppression of
      enzymatic degradation with MMPs/TIMP-1 and alpha2beta1-integrin-mediated
      endocytosis. Those alterations are likely mediated through the cellular signaling
      pathways of ERK1/2 and nuclear factor kappaB. These synergistic effects may cause
      collagen accumulation, leading to GO.

PMID- 15948690
TI  - Aberrant neutrophil reactions in periodontitis.
AB  - BACKGROUND: The aim of this study was to compare the activity of neutrophilic
      granulocytes in patients with severe periodontitis and patients with gingivitis
      alone. METHODS: The study population comprised 22 patients with gingivitis and 44
      with periodontitis. Samples of gingival crevicular fluid (GCF) were collected
      from untreated patients with gingivitis and from shallow and deep pockets in
      untreated patients with periodontitis. GCF samples were analyzed for lactoferrin,
      elastase, matrix metalloproteinase-8 and -9, and collagenolytic activity.
      RESULTS: The free elastase activity and the neutrophil activity, estimated as the
      ratio between elastase and lactoferrin, were significantly higher in the samples
      from the periodontitis patients. These differences were also observed in shallow
      pockets in periodontitis patients compared to similar pockets in patients with
      gingivitis. CONCLUSION: This study shows higher levels of free elastase in
      untreated patients with periodontitis, relative to inflammation-matched controls,
      which may explain the tissue destruction seen in periodontitis.

PMID- 15948691
TI  - Nitric oxide synthase inhibition prevents alveolar bone resorption in
      experimental periodontitis in rats.
AB  - BACKGROUND: Periodontitis is the most frequent cause of tooth loss in adults.
      Nitric oxide (NO) has been linked to bone resorption mechanisms during
      inflammation processes. The aim of this study was to investigate the effect of
      NOS (NO synthase) inhibitors in the alveolar bone loss in an experimental
      periodontitis disease (EPD) model. METHODS: Wistar rats were subjected to a
      ligature placement around the second upper left molars and were sacrificed at 11
      days. Alveolar bone loss was evaluated by the sum of distances between the cusp
      tips and the alveolar bone along the axis of each molar root, subtracting from
      the contralateral side. Histopathological analysis was based on cell influx,
      alveolar bone, and cementum integrity. Leukogram was performed at 6 hours and 1,
      7, and 11 days after the EPD induction. Groups were treated with the NOS
      inhibitors, aminoguanidine (AG) (2.5 to 10 mg/kg/d), or L-arginine methyl ester
      (L-NAME, 5 to 20 mg/kg/d) intraperitoneally (i.p.), 1 hour before the EPD
      induction and daily for 11 days. Controls received only saline (EPD group). As
      controls for L-NAME specificity, groups were co-treated with either L-arginine
      (150 to 600 mg/kg/d) or D-arginine (600 mg/kg/d) and L-NAME (20 mg/kg/d).
      Different groups were used for morphometric and histopathological analysis.
      RESULTS: Both L-NAME and AG significantly and dose-dependently inhibited the
      alveolar bone loss as compared to EPD group. L-NAME (20 mg/kg/d) reduced the
      alveolar bone loss by 50%, whereas AG (5 mg/kg/d) reduced it by 47% compared to
      EPD. This result was coupled to a significant reduction of cell influx to the
      periodontium, as well as to the preservation of alveolar bone and cementum, seen
      at histopathology, for both compounds. The co-administration of L-arginine, but
      not of D-arginine reversed L-NAME effects. CONCLUSION: These data provide
      evidence that NOS inhibitors prevent inflammatory bone resorption in experimental
      periodontitis.

PMID- 15948693
TI  - Outer membrane vesicles from Porphyromonas gingivalis affect the growth and
      function of cultured human gingival fibroblasts and umbilical vein endothelial
      cells.
AB  - BACKGROUND: The purpose of this study was to examine the effects of outer
      membrane vesicles (OMV) obtained from Porphyromonas gingivalis (Pg) on the growth
      and function of human gingival fibroblasts (HGF) and human umbilical vein
      endothelial cells (HUVEC). METHODS: OMV were obtained from a cell-free growth
      medium of Pg ATCC 33277 by 40% NH2SO4 precipitation and ultracentrifugation. Cell
      proliferation was measured by 3H-thymidine incorporation into growing HGF and
      HUVEC. Endothelial cell function was determined by their capacity to form a
      network of capillary tubes on an extracellular matrix (ECM). RESULTS:
      Proliferating HGF and HUVEC demonstrated a significant dose-dependent inhibition
      of 3H-thymidine uptake when cultured with 0 to 40 microg/ml of OMV protein. HGF
      and HUVEC showed an IC50 of growth of about 9.0 microg/ml and 4.5 microg/ml of
      OMV protein, respectively. Capillary tube formation by HUVEC cultured on an ECM
      was suppressed by 70% to 80% with 5 microg/ml OMV protein after 18 hours of
      incubation. The presence of proteolytic enzymes in the OMV did not contribute to
      capillary tube disruption, since blocking enzyme activity with specific
      inhibitors did not reduce the suppression of capillary tube formation. After
      heating at 90 degrees C for 5 minutes, OMV significantly lost their capacity to
      suppress capillary tube formation. CONCLUSIONS: OMV significantly inhibit the
      proliferation of cultured HGF and HUVEC in a dose-dependent manner. OMV
      suppressed the capillary tube formation by cultured HUVEC. The factor(s) appeared
      to be a protein and not endotoxin because its inhibitory activity was markedly
      reduced by heat inactivation. These studies suggest that OMV contribute to
      chronic periodontitis by suppressing cell proliferation and revascularization in
      periodontal tissues.

PMID- 15948692
TI  - Effect of neutrophil apoptosis on monocytic cytokine response to Porphyromonas
      gingivalis lipopolysaccharide.
AB  - BACKGROUND: Neutrophil apoptosis may play a critical role in the resolution of
      inflammation by stimulating anti-inflammatory cytokine generation from monocytes.
      In this study, we investigated the effect of apoptotic neutrophils on interleukin
      (IL)-10 and IL-1beta production from monocytes in response to Porphyromonas
      gingivalis lipopolysaccharide. METHODS: Peripheral blood neutrophils from healthy
      individuals were isolated by sodium diatrizoate density gradient centrifugation.
      In order to induce apoptosis, neutrophils were cultured for 24 hours in modified
      Dulbecco's medium supplemented with 10% autologous serum. Cell apoptosis was
      quantified by Annexin V positivity and loss of CD16 expression on the cell
      surface. Peripheral blood mononuclear cells were isolated from the same subjects;
      monocytes were purified by magnetic cell sorting and cultured with or without
      apoptotic or fresh neutrophils. Lipopolysaccharide from Porphyromonas gingivalis
      was used for cell stimulation. IL-1beta and IL-10 levels in supernatants were
      determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-10
      generation was significantly increased in monocytes cultured with apoptotic
      neutrophils compared to monocytes alone or cocultured with fresh neutrophils (P
      <0.05). IL-1beta was suppressed both in resting and lipopolysaccharide-stimulated
      monocytes in the presence of apoptotic neutrophils compared to monocytes alone or
      monocytes cultured with fresh neutrophils at all time points (P <0.05).
      CONCLUSION: Neutrophil apoptosis provides a signal to monocytes, changing the
      phenotype of the monocyte resulting in the production of anti-inflammatory
      cytokines and suppression of proinflammatory cytokines in response to
      lipopolysaccharide.

PMID- 15948694
TI  - Pain experienced by patients during periodontal recall examination using thinner
      versus thicker probes.
AB  - BACKGROUND: The aim of the present study, performed during periodontal recall
      visits, was to compare the levels of pain experienced by patients during
      periodontal probing using probes with tip diameters of either 0.40 mm or 0.63 mm.
      METHODS: Three groups of 20 adult patients were examined by three different
      therapists. Diagonal maxillary/mandibular quadrants were probed with a 0.40 mm
      and a 0.63 mm probe, respectively. At the completion of probing of each quadrant,
      the patients were asked to describe their pain using a visual analog scale (VAS).
      RESULTS: Most patients showed low VAS pain scores for both probes. However, using
      an arbitrary threshold of VAS > or =40 mm to indicate significant pain, some
      patients had a painful experience. Lower median pain responses following probing
      with the 0.63 mm probe compared to the 0.40 mm probe were observed for patients
      of therapist 1, and for the quartile of all 60 patients that showed the highest
      VAS scores. For therapist 2 and 3 groups, no differences were found. The pain
      levels expressed by the three groups of patients varied, confirming results of
      our previous studies, which also observed differences in patients' pain
      experiences following probing by different therapists. CONCLUSIONS: The ability
      to deliver dental care with a minimum of patient discomfort would seem to be an
      essential part of the skills of individual clinicians. We would like to suggest
      that dental therapists periodically evaluate this part of their skill by asking
      patients to express their pain experiences following various procedures using VAS
      scales.

PMID- 15948695
TI  - Ability of examiners to estimate the pain experienced by patients from probing
      during initial periodontal examination.
AB  - BACKGROUND: The aims of the present study were to identify the level of pain
      experienced by patients from probing during periodontal examination, and to
      determine to what extent the examining periodontist and the dental assistant
      could estimate the degree of pain experienced by the patients. METHODS: For each
      of three periodontists, 20 patients referred for periodontal diagnosis and
      treatment were selected. The periodontist carried out his examination, which
      included probing at six sites per tooth. Following probing, the patients rated
      the pain using a visual analog scale (VAS). The periodontist and the dental
      assistant who helped out during the examination independently rated the pain
      level they perceived that each patient experienced, also using a VAS. RESULTS:
      Most patients showed low pain responses to probing. However, using an arbitrary
      threshold of VAS > or =40 mm to indicate significant pain, some patients had a
      painful experience. Differences were observed between the pain levels expressed
      by the three groups of patients. While two of the three periodontists were able
      to appraise the pain experienced by their patients, the third was not.
      CONCLUSIONS: It seems important that the periodontist at the first encounter with
      the patient should be sensitive to the discomfort the examination may entail.
      This may influence the patients' decision to accept the required treatment, and
      may also affect the patients' attitude to and co-operation with the subsequent
      treatment.

PMID- 15948696
TI  - Enhanced root planing and systemic metronidazole administration improve clinical
      and microbiological outcomes in a two-step treatment procedure.
AB  - BACKGROUND: Recently we described a non-surgical two-step treatment concept, in
      which we distinguished between a first scaling and root planing step (SRP) and an
      additional second enhanced root planing step (ERP). Until now it is difficult to
      determine how often a root surface should be instrumented during ERP. METHODS:
      The aim of the present study was to investigate the outcomes after different root
      planing intensities during ERP in 37 patients with aggressive periodontitis after
      SRP. During ERP a full-mouth root planing was performed. The patients were
      randomly assigned to one of two root planing regimens (group 1, N = 12 and group
      2, N = 11), based on number of curet strokes per root surface (instrumentation
      frequency, IF) and probing depth. Group 1: PD 1 to 3.5 mm, 4 IF (for group 2, 8
      IF); PD 4 to 6 mm, 8 IF (group 2, 14 IF); PD 6.5 to 9 mm, 12 IF (group 2, 20 IF);
      and PD >9 mm, 16 IF (group 2, 24 IF). Group 3 patients (controls; N = 14)
      received only the initial SRP. All three groups received the same adjunctive
      systemic antibiotic treatment. RESULTS: In all groups, the results showed
      statistically significant differences in PD and clinical attachment level (CAL)
      after 6 and 24 months compared to baseline data. Compared with the controls, a
      significant reduction in PD was observed in groups 1 and 2. The reduction in mean
      PD was distinctly greater in group 2 (higher IF). Furthermore, Porphyromonas
      gingivalis (Pg) and Actinobacillus actinomycetemcomitans (Aa) were completely
      suppressed in group 2 after 24 months. CONCLUSIONS: The present results show that
      the extent of root planing has a distinct influence on treatment outcomes.
      Patients treated with the highest instrumentation frequency showed the best long
      term results.

PMID- 15948698
TI  - Sense of coherence as a determinant of toothbrushing frequency and level of oral
      hygiene.
AB  - BACKGROUND: Antonovsky's salutogenic theory seeks to find general health
      promoting factors in individuals as distinct from characteristics that function
      as risks for specific diseases. A central construct of the theory is sense of
      coherence (SOC). Individuals with a strong SOC have the ability to define events
      as less stressful (because of comprehensibility); to mobilize resources to deal
      with encountered stressors (manageability); and to possess the motivation,
      desire, and commitment to cope (meaningfulness). Our aim is to investigate
      whether SOC, self-reported toothbrushing frequency, and objectively assessed
      levels of oral hygiene are related. METHODS: The sample of the present study
      consisted of 4,131 30- to 64-year-old dentate Finns belonging to a large
      nationally representative sample. The questionnaire and home interview included
      information about socioeconomic and demographic factors, behavioral variables,
      such as oral health behaviors (toothbrushing frequency), and a 12-item SOC scale,
      used here as a unidimensional measure categorized into quintiles. The level of
      oral hygiene was measured during clinical oral examination. Chi-square test,
      ordinal, and ordinary logistic regression analyses were used. RESULTS: Subjects
      belonging to the strongest SOC quintile were found to be significantly more often
      two, or more, times a day brushers compared to those with less strong SOC. After
      controlling for toothbrushing frequency, sociodemographic and socioeconomic
      factors, smoking habits, and number of teeth, both strong and moderate levels of
      SOCs were also found to be related to a good level of oral hygiene compared with
      moderate and poor levels of oral hygiene. Furthermore, subjects within the
      weakest SOC quintile were found to have significantly more often than others poor
      levels of oral hygiene. CONCLUSIONS: Our results suggest that a weak sense of
      coherence increases both the probability of having a poor level of oral hygiene
      and a frequency of toothbrushing of less than once a day. This and the theory
      concerning the development of SOC suggest that sense of coherence may be taken as
      a determinant of both the frequency and the quality of toothbrushing.

PMID- 15948697
TI  - Effect of topical cimetidine rinse on gingival crevicular neutrophil leukocyte
      function.
AB  - BACKGROUND: Three coordinated mechanism-of-action clinical studies were conducted
      to examine the effects of topical cimetidine rinse on neutrophil function in the
      gingival crevice. METHODS: The first study was a randomized, double-blind,
      placebo-controlled, 28-day experimental gingivitis study involving 21 healthy
      adults, in which subjects rinsed twice a day with placebo or 0.5% cimetidine
      rinses. At baseline and days 14, 21, and 28, neutrophils were harvested from
      prespecified gingival sulcular sites, purified, stained, and examined by
      trifluorochrome phagocytosis and killing microassay. The second and third studies
      were placebo-controlled, 9-week, three-period (each of 3 weeks' duration),
      longitudinal studies involving seven and nine adults with moderate periodontitis,
      respectively. Subjects rinsed twice a day during periods 1 and 3 with placebo and
      during period 2 with 0.5% cimetidine. At baseline and weekly intervals,
      neutrophils were harvested from prespecified periodontal pockets, purified,
      stained, and examined by trifluorochrome phagocytosis and killing microassay in
      the second study. In the third study, neutrophils were examined
      spectrophotometrically for superoxide production and in a luminol-enhanced
      chemiluminescence assay. RESULTS: In the first study, the mean number of
      phagocytosing neutrophils was statistically significantly increased (P = 0.016)
      in the cimetidine group (31.1 cells/subject) versus the placebo group (13.7
      cells/subject) at day 28. In addition, a statistically significant increase (P =
      0.036) in bacterial killing was observed in the cimetidine rinse group; in the
      cimetidine group, 63.4% of bacteria in the neutrophils were killed compared to
      46.2% in the placebo group. Additional data from the other two studies support
      these findings. CONCLUSION: Collectively, these studies provide evidence that
      topical 0.5% cimetidine oral rinse enhances the antibacterial function of
      crevicular neutrophils.

PMID- 15948699
TI  - The clinical effectiveness of 6 mm diameter implants.
AB  - BACKGROUND: Five- and 6 mm diameter screw-type endosseous implants have been used
      for the last decade. While some studies have reported very promising results (94%
      to 98% success rate), others have demonstrated survival rates below those
      clinically acceptable (75% to 87%). Moreover, such implants have been associated
      with increased cervical bone resorption and thread exposure. METHODS: Between
      June 1999 and July 2003, 43 patients received treatment with 6 mm diameter
      tapered hydroxyapatite (HA)-coated implants. A total of 45 implants were placed.
      All patients were recalled annually after implant exposure. One patient was lost
      to follow-up after 1 year. Forty-four implants were evaluated at the recall
      examinations. All implants supported a fixed prosthesis; in the majority of
      patients (35 implants), it was a single-tooth fixed prosthesis. The mean loading
      time was 23.4 months (range, 1 to 54 months). RESULTS: No implants were lost
      during the loading period. The overall survival rate was 100%. Crestal bone
      remodeling was examined using periapical radiographs. After a mean of 23.4 months
      in function, only one implant presented bone loss beyond the first thread.
      CONCLUSIONS: This study showed that high survival rates can be obtained after
      prosthetic treatment with 6 mm-wide tapered HA-coated implants. Long-term
      prospective studies are needed to confirm these results.

PMID- 15948700
TI  - Immediate functional loading of edentulous maxilla: a 5-year retrospective study
      of 388 titanium implants.
AB  - BACKGROUND: Immediate functional loading is a new surgical-prosthetic technique
      that can be used extensively in implant placement. Because of a lack of
      experimental reports regarding edentulous maxilla, we decided to evaluate the
      survival rate of immediately loaded dental implants in this area. METHODS: Forty
      three patients (44.4% male) with a median age of 55 years receiving 388 implants
      (mean 9.0 per case) were enrolled in this study. Cross-arch acrylic provisional
      restorations were performed in the same stage. Data were analyzed by Kaplan-Meier
      product limit estimation. Stratification of implants survival was performed for
      the available variables of interest, and comparisons were analyzed by a log rank
      test. Cox algorithm was used for multivariable analysis. RESULTS: At 5-year
      follow-up, the crude survival rate (overall survival not stratified according to
      any available variable) was 98%. All failures occurred within 6 months from
      loading. We found differences in survival relating to: 1) implant diameter
      (99.37% for diameter < or =5.25 mm and 93.75% for diameter >5.25 mm); 2) number
      of implants (99.29% for < or =10 implants and 96.30% for >10); and 3) gender
      (97.08% and 99.54% for males and females, respectively). Cox regression analysis
      showed that diameter of implants adjusted for patient age and gender was
      associated to an average risk of failure (hazard rate) of 3.13 (P value = 0.042,
      95% confidence interval 1.04 to 9.43) per mm (from 3 to 6.5). CONCLUSIONS:
      Immediate functional loading is a reliable surgical-prosthetic procedure in
      edentulous maxillae. Implants with wider diameter are associated with a higher
      risk of failure.

PMID- 15948701
TI  - A combined therapeutic approach to manage oral halitosis: a 3-month prospective
      case series.
AB  - BACKGROUND: Clinical research assessing different therapeutic protocols aimed at
      treating oral halitosis is scarce. The aim of this study was to evaluate the
      effects of a combined mechanical and pharmacological approach to treat oral
      halitosis on clinical and microbiological outcomes on patients followed for 3
      months. METHODS: Nineteen subjects with oral malodor participated. At baseline,
      all subjects completed a questionnaire and carried out an examination including
      full-mouth organoleptic and volatile sulfur compound (VSC) levels and the Winkel
      tongue coating index. Standard periodontal outcome variables were assessed at six
      teeth. Standardized microbiological samples of subgingival plaque, unstimulated
      saliva, and tongue coating were obtained for culture analysis. The treatment
      protocol included supragingival prophylaxis; instructions in oral hygiene
      (toothbrushing, interproximal cleaning, and tongue scraping); and gargling with a
      mouthrinse containing chlorhexidine, cetylpiridinium chloride, and zinc lactate.
      The same outcome variables were registered 1 and 3 months after baseline.
      RESULTS: Statistically significant reductions in organoleptic scores (P <0.001),
      VSC levels (P <0.05), and tongue coating index (P <0.05) were observed after 1
      and 3 months. Mean probing depth and plaque levels also demonstrated significant
      reductions after 3 months (P <0.05). Total anaerobic counts were significantly
      reduced at all three locations after 1 month (P <0.05), and in samples from
      tongue coating and subgingival plaque at 3 months (P <0.05). Aerobic counts were
      significantly reduced in saliva at 1 month (P <0.05), and the anaerobic/aerobic
      ratio significantly increased in the tongue samples. Among the selected pathogens
      evaluated, Porphyromonas gingivalis was the most affected of the three microflora
      evaluated. CONCLUSIONS: The evaluated therapeutic approach demonstrated its
      efficacy in the management of oral halitosis, demonstrating statistically
      significant improvements in both organoleptic and VSC values at 1 and 3 months.
      The proposed clinical protocol significantly affected the microbial composition
      in tongue coating, saliva, and subgingival microflora.

PMID- 15948702
TI  - Tetracycline fibers as an adjunct in the treatment of nifedipine-induced gingival
      enlargement.
AB  - BACKGROUND: The hypothesis that nifedipine-induced gingival enlargement in
      periodontitis patients can be treated with the adjunctive use of tetracycline
      (TCN) fibers was tested in this study. METHODS: Ten patients (mean age 66 +/- 4
      years) with chronic periodontitis combined with nifedipine-induced gingival
      enlargement participated. Full mouth recordings of clinical parameters (probing
      depth, clinical attachment level, bleeding on probing, presence or absence of
      plaque) were assessed at baseline and gingival enlargement was estimated from
      casts. Participants were instructed in proper oral hygiene and received
      supragingival scaling before being reassessed 1 month later. They subsequently
      received full-mouth scaling and root planing followed by the immediate placement
      of TCN fibers in all pockets >5 mm. Clinical parameters were reassessed at 3, 6,
      and 12 months after completion of treatment. RESULTS: TCN fiber placement was
      well tolerated by patients. All clinical parameters recorded displayed
      significant improvements after treatment, and they were preserved for the 12
      month experimental period. A significant reduction of the percentage of pockets
      >5 mm was noticed after treatment. The reduction of enlargement was still
      observed at 12 months despite patients not achieving optimal oral hygiene.
      CONCLUSION: Placement of tetracycline fibers as an adjunct to mechanical
      treatment is an option for the non-invasive therapy of nifedipine-induced
      gingival enlargement in periodontitis patients whose general medical condition
      and concomitant ailments do not favor a surgical approach.

PMID- 15948703
TI  - Enzymatic DNA methylation is an epigenetic control for genetic functions of the
      cell.
AB  - In eukaryotic cells nuclear DNA is subjected to enzymatic methylation resulting
      in formation of 5-methylcytosine residues mainly in CG and CNG sequences. In
      plants and animals, this DNA methylation is species-, tissue-, and organelle
      specific. It changes (diminishes) with age and is regulated by hormones. On the
      other hand, genome methylation can control hormonal signal. There are replicative
      and post-replicative DNA methylations. They are served by multiple DNA
      methyltransferases with different site specificity. Replication is accompanied by
      appearance of hemi-methylated sites in DNA; pronounced asymmetry of DNA chain
      methylation disappears at the end of the cell cycle; a model of regulation of
      replication by DNA methylation is suggested. DNA methylation controls all genetic
      processes in the cell (replication, transcription, DNA repair, recombination,
      gene transposition) and it is a mechanism of cell differentiation, gene
      discrimination, and silencing. Prohibition of DNA methylation stops development
      (embryogenesis), switches on apoptosis, and is usually lethal. Distortions in DNA
      methylations result in cancerous cell transformation, and the DNA methylation
      pattern is one of the safe cancer diagnostics at early stages of carcinogenesis.
      The malignant cell has a different DNA methylation pattern and a set of DNA
      methyltransferase activities expressed as compared with normal cells. Inhibition
      of DNA methylation in plants is accompanied by induction of genes of seed storage
      proteins and flowering. In eukaryotes one and the same gene can be methylated
      both on cytosine and adenine residues; thus, there are, at least, two different
      and probably interdependent systems of DNA methylation in the cell. First higher
      eukaryotic adenine DNA-methyltransferase was isolated from plants; this enzyme
      methylates DNA with formation of N6-methyladenine residues in the sequence TGATCA
      --> TGm6ATCA. Plants have AdoMet-dependent endonucleases sensitive to DNA
      methylation status; therefore, like microorganisms, plants seem to have a
      restriction-modification (R-S) system. Revelation of an essential role of DNA
      methylation in the regulation of genetic processes has laid a foundation for and
      materialized epigenetics and epigenomics.

PMID- 15948704
TI  - DNA methylation and epigenotypes.
AB  - The science of epigenetics is the study of all those mechanisms that control the
      unfolding of the genetic program for development and determine the phenotypes of
      differentiated cells. The pattern of gene expression in each of these cells is
      called the epigenotype. The best known and most thoroughly studied epigenetic
      mechanism is DNA methylation, which provides a basis both for the switching of
      gene activities, and the maintenance of stable phenotypes. The human epigenome
      project is the determination of the pattern of DNA methylation in multiple cell
      types. Some methylation sites, such as those in repeated genetic elements, are
      likely to be the same in all cell types, but genes with specialized functions
      will have distinct patterns of DNA methylation. Another project for the future is
      the study of the reprogramming of the genome in gametogenesis and early
      development. Much is already known about the de novo methylation of tumor
      suppressor genes in cancer cells, but the significance of epigenetic defects
      during ageing and in some familial diseases remains to be determined.

PMID- 15948705
TI  - On the biological significance of DNA methylation.
AB  - This chapter presents a personal account of the work on DNA methylation in viral
      and mammalian systems performed in the author's laboratory in the course of the
      past thirty years. The text does not attempt to give a complete and meticulous
      account of the many relevant and excellent reports published by many other
      laboratories, so it is not a review of the field in a conventional sense. The
      choice of viral model systems in molecular biology is well founded. Over many
      decades, viruses have proven their invaluable and pioneering role as tools in
      molecular genetics. When our interest turned to the demonstration of genome-wide
      patterns of DNA methylation, we focused mainly on the human genome. The following
      topics in DNA methylation will be treated in detail: (i) the de novo methylation
      of integrated foreign genomes; (ii) the long-term gene silencing effect of
      sequence-specific promoter methylation and its reversal; (iii) the properties and
      specificity of patterns of DNA methylation in the human genome and their possible
      relations to pathogenesis; (iv) the long-range global effects on cellular DNA
      methylation and transcriptional profiles as a consequence of foreign DNA
      insertion into an established genome; (v) the patterns of DNA methylation can be
      considered part of a cellular defense mechanism against foreign or repetitive
      DNA; what role has food-ingested DNA played in the elaboration of this mechanism?

PMID- 15948706
TI  - Methylation of DNA--one of the major epigenetic markers.
AB  - Regulation of gene expression is a complex process. It includes a great number of
      steps from control of mRNA synthesis to posttranslational modification of
      proteins. Epigenetic events play essential roles in regulation of transcription.
      In this review, we concentrate on methylation of DNA as one of the important
      epigenetic marks. It is well known that DNA methylation is associated with closed
      chromatin state and, therefore, repressed, inactive genes. Here we describe major
      processes that depend on DNA methylation: imprinting, X-inactivation, and
      oncogenesis. Also we describe a number of known methyl-DNA-binding proteins and
      links between methylation of DNA and higher-order chromatin structure.

PMID- 15948707
TI  - DNA methylation and demethylation as targets for anticancer therapy.
AB  - Cancer growth and metastasis require the coordinate change in gene expression of
      different sets of genes. While genetic alterations can account for some of these
      changes, it is becoming evident that many of the changes in gene expression
      observed are caused by epigenetic modifications. The epigenome consists of the
      chromatin and its modifications, the "histone code" as well as the pattern of
      distribution of covalent modifications of cytosines residing in the dinucleotide
      sequence CG by methylation. Although hypermethylation of tumor suppressor genes
      has attracted a significant amount of attention and inhibitors of DNA methylation
      were shown to activate methylated tumor suppressor genes and inhibit tumor
      growth, demethylation of critical genes plays a critical role in cancer as well.
      This review discusses the emerging role of demethylation in activation of pro
      metastatic genes and the potential therapeutic implications of the demethylation
      machinery in metastasis.

PMID- 15948708
TI  - DNA-[adenine] methylation in lower eukaryotes.
AB  - DNA methylation in lower eukaryotes, in contrast to vertebrates, can involve
      modification of adenine to N6-methyladenine (m6A). While DNA-[cytosine]
      methylation in higher eukaryotes has been implicated in many important cellular
      processes, the function(s) of DNA-[adenine] methylation in lower eukaryotes
      remains unknown. I have chosen to study the ciliate Tetrahymena thermophila as a
      model system, since this organism is known to contain m6A, but not m5C, in its
      macronuclear DNA. A BLAST analysis revealed an open reading frame (ORF) that
      appears to encode for the Tetrahymena DNA-[adenine] methyltransferase (MTase),
      based on the presence of motifs characteristic of the enzymes in prokaryotes.
      Possible biological roles for DNA-[adenine] methylation in Tetrahymena are
      discussed. Experiments to test these hypotheses have begun with the cloning of
      the gene. Orthologous ORFs are also present in three species of the malarial
      parasite Plasmodium. They are compared to one another and to the putative
      Tetrahymena DNA-[adenine] MTase. The gene from the human parasite P. falciparum
      has been cloned.

PMID- 15948709
TI  - Epigenetic changes and repositioning determine the evolutionary fate of
      duplicated genes.
AB  - Consideration of epigenetic silencing, perhaps by DNA methylation, led to an
      epigenetic complementation (EC) model for evolution by gene duplication (Rodin
      and Riggs (2003) J. Mol. Evol., 56, 718-729). This and subsequent work on genome
      wide analyses of gene duplicates in several eukaryotic species pointed to a
      fundamental link between localization in the genome, epigenetic regulation of
      expression, and the evolutionary fate of new redundant gene copies, which can be
      either non- or neo-functionalization. Our main message in this report is that
      repositioning of a new duplicate to an ectopic site epigenetically alters its
      expression pattern, and concomitantly the rate and direction of mutations.
      Furthermore, comparison of syntenic vs. non-syntenic pairs of gene duplicates of
      different age unambiguously indicates that repositioning saves redundant gene
      duplicates from pseudogenization and hastens their evolution towards a new
      development-time and tissue-specific pattern of function.

PMID- 15948710
TI  - The controversial denouement of vertebrate DNA methylation research.
AB  - The study of the biological role of DNA methylation in vertebrates has involved
      considerable controversy. Research in this area has proceeded well despite the
      complexity of the subject and the difficulties in establishing biological roles,
      some of which are summarized in this review. Now there is justifiably much more
      interest in DNA methylation than previously, and many more laboratories are
      engaged in this research. The results of numerous studies indicate that some
      tissue-specific differences in vertebrate DNA methylation help maintain patterns
      of gene expression or are involved in fine-tuning or establishing expression
      patterns. Therefore, vertebrate DNA methylation cannot just be assigned a role in
      silencing transposable elements and foreign DNA sequences, as has been suggested.
      DNA methylation is clearly implicated in modulating X chromosome inactivation and
      in establishing genetic imprinting. Also, hypermethylation of CpG-rich promoters
      of tumor suppressor genes in cancer has a critical role in downregulating
      expression of these genes and thus participating in carcinogenesis. The complex
      nature of DNA methylation patterns extends to carcinogenesis because global DNA
      hypomethylation is found in the same cancers displaying hypermethylation
      elsewhere in the genome. A wide variety of cancers display both DNA
      hypomethylation and hypermethylation, and either of these types of changes can be
      significantly associated with tumor progression. These findings and the
      independence of cancer-linked DNA hypomethylation from cancer-linked
      hypermethylation strongly implicate DNA hypomethylation, as well as
      hypermethylation, in promoting carcinogenesis. Furthermore, various DNA
      demethylation methodologies have been shown to increase the formation of certain
      types of cancers in animals, and paradoxically, DNA hypermethylation can cause
      carcinogenesis in other model systems. Therefore, there is a need for caution in
      the current use of demethylating agents as anti-cancer drugs. Nonetheless, DNA
      demethylation therapy clearly may be very useful in cases where better
      alternatives do not exist.

PMID- 15948711
TI  - Methylation of the tumor suppressor gene RASSF1A in human tumors.
AB  - Loss of heterozygosity of a segment at 3p21.3 is frequently observed in lung
      cancer and several other carcinomas. We have identified the Ras-association
      domain family 1A gene (RASSF1A), which is localized at 3p21.3 in a minimum
      deletion sequence. De novo methylation of the RASSF1A promoter is one of the most
      frequent epigenetic inactivation events detected in human cancer and leads to
      silencing of RASSF1A expression. Hypermethylation of RASSF1A was frequently found
      in most major types of human tumors including lung, breast, prostate, pancreas,
      kidney, liver, cervical, thyroid and many other cancers. The detection of RASSF1A
      methylation in body fluids such as serum, urine, and sputum promises to be a
      useful marker for early cancer detection. The functional analysis of RASSF1A
      reveals a potential involvement of this protein in apoptotic signaling,
      microtubule stabilization, and cell cycle progression.

PMID- 15948712
TI  - The language of methylation in genomics of eukaryotes.
AB  - Background studies have shown that 6-methylaminopurine (m6A) and 5-methylcytosine
      (m5C), detected in DNA, are products of its post-synthetic modification. At
      variance with bacterial genomes exhibiting both, eukaryotic genomes essentially
      carry only m5C in m5CpG doublets. This served to establish that, although a
      slight extra-S phase asymmetric methylation occurs de novo on 5'-CpC-3'/3'GpG-5',
      5'-CpT-3'/3'-GpA-5', and 5'-CpA-3'/3'-GpT-5' dinucleotide pairs, a heavy
      methylation during S involves Okazaki fragments and thus semiconservatively newly
      made chains to guarantee genetic maintenance of -CH3 patterns in symmetrically
      dimethylated 5'-m5CpG-3'/3'-Gpm5C-5' dinucleotide pairs. On the other hand,
      whilst inverse correlation was observed between bulk DNA methylation, in S, and
      bulk RNA transcription, in G1 and G2, probes of methylated DNA helped to discover
      the presence of coding (exon) and uncoding (intron) sequences in the eukaryotic
      gene. These achievements led to the search for a language that genes regulated by
      methylation should have in common. Such a deciphering, initially providing
      restriction minimaps of hypermethylatable promoters and introns vs.
      hypomethylable exons, became feasible when bisulfite methodology allowed the
      direct sequencing of m5C. It emerged that, while in lymphocytes, where the
      transglutaminase gene (hTGc) is inactive, the promoter shows two fully methylated
      CpG-rich domains at 5 and one fully unmethylated CpG-rich domain at 3' (including
      the site +1 and a 5'-UTR), in HUVEC cells, where hTGc is active, in the first CpG
      rich domain of its promoter four CpGs lack -CH3: a result suggesting new
      hypotheses on the mechanism of transcription, particularly in connection with
      radio-induced DNA demethylation.

PMID- 15948713
TI  - Study of tissue-specific CpG methylation of DNA in extended genomic loci.
AB  - Modern approaches for studies on genome functioning include investigation of its
      epigenetic regulation. Methylation of cytosines in CpG dinucleotides is an
      inherited epigenetic modification that is responsible for both functional
      activity of certain genomic loci and total chromosomal stability. This review
      describes the main approaches for studies on DNA methylation. Under consideration
      are site-specific approaches based on bisulfite sequencing and methyl-sensitive
      PCR, whole-genome approaches aimed at searching for new methylation hot spots,
      and also mapping of unmethylated CpG sites in extended genomic loci.

PMID- 15948714
TI  - Purkinje cell protein-2 (Pcp2) stimulates differentiation in PC12 cells by
      Gbetagamma-mediated activation of Ras and p38 MAPK.
AB  - Purkinje cell protein-2 (Pcp2 or L7) is highly expressed in cerebellar Purkinje
      cells and retinal bipolar neurons and interacts with the Galpha(i/o) family of G
      proteins. Although the expression pattern of Pcp2 in the developing central
      nervous system suggests a role in differentiation, its function remains unknown.
      We established Tet-off inducible expression of Pcp2 in PC12 cells (rat
      pheochromocytoma cells) to determine whether Pcp2 regulates neuronal
      differentiation. Utilizing a polyclonal antibody, Pcp2 was localized in the cell
      body and throughout neurites of differentiated PC12 cells, similar to its
      localization in cerebellar Purkinje cells. Pcp2 expression in PC12 cells
      stimulated process formation (5-fold) and NGF (nerve growth factor)-stimulated
      neurite length (2-fold). Under basal conditions, Pcp2-PC12 cells demonstrated a 5
      fold increase in Ras activation relative to non-induced PC12 cells and there was
      no change in extracellular-signal-regulated kinase 1/2 activity with Pcp2
      expression. However, Pcp2 induction led to a >3-fold increase in basal p38 MAPK
      (mitogen-activated protein kinase) activity and the addition of NGF significantly
      stimulated both Ras and p38 MAPK in Pcp2-PC12 cells relative to the controls.
      Pretreatment of Pcp2-PC12 cells with the p38-specific inhibitor SB203580 blocked
      both the increased neurite formation and NGF-stimulated neurite growth. Pertussis
      toxin treatment had no effect on neurite growth in control cells, but completely
      blocked Pcp2-mediated increased neurite growth. Transient transfection of the
      beta-adrenergic receptor kinase C-terminus to prevent signalling through
      Gbetagamma in Pcp2-PC12 cells also inhibited the Pcp2-induced phenotype and
      reduced the Pcp2-stimulated Ras activation. Taken together, these findings
      demonstrate that Pcp2 induces differentiation in PC12 cells, in part through
      Gbetagamma-mediated Ras and p38 MAPK activation and suggest the potential for
      similar signalling mechanisms in Purkinje cells.

PMID- 15948715
TI  - Endothelial function and baroreflex sensitivity according to the oral glucose
      tolerance test in patients with coronary artery disease and normal fasting
      glucose levels.
AB  - Endothelial dysfunction and reduced BRS (baroreflex sensitivity) may be present
      in patients with CAD (coronary artery disease). The normal fasting glucose level
      does not exclude abnormal glucose metabolism in patients with CAD. The aim of
      present study was to evaluate endothelial function and BRS according to glucose
      metabolism in patients with normal fasting plasma glucose and stable CAD
      subjected to PTCA (percutaneous transluminal coronary angioplasty). Forty-six
      consecutive patients who underwent elective PTCA were studied (37 men; mean age
      56 years). Endothelial function was assessed non-invasively using the arterial
      vasodilator response to salbutamol (albuterol). BRS was measured using a cross
      correlation method. The extent of coronary narrowing was estimated by calculation
      of the Gensini score. All patients underwent a 75 g OGTT (oral glucose tolerance
      test). IGT (impaired glucose tolerance) or diabetes was present in approx. 60% of
      patients. The vasodilator response to salbutamol, as a measure of endothelial
      dysfunction, was significantly impaired in patients with IGT or diabetes compared
      with those with normal glucose tolerance (-0.5+/-1.6% compared with -7.9+/-2.2;
      P=0.01). Glucose metabolism and age were significant predictors of endothelial
      dysfunction (R(2)=35.2%, P=0.02). BRS did not differ significantly between
      patients with normal glucose tolerance and those with IGT or diabetes (6.9+/-1.2
      compared with 6.1+/-0.6 ms/mmHg respectively; P=0.669). BRS was negatively
      correlated with age (r=-0.34, P=0.021) and the Gensini score (r=-0.34, P=0.022).
      The significant predictors of BRS were Gensini score, age and past myocardial
      infarction (R(2)=37.02%, P=0.002). Patients with established CAD, normal fasting
      glucose and IGT or diabetes demonstrated impaired endothelial function which did
      not correlate with the extent of coronary artery involvement. Conversely, BRS in
      the study population was not affected by glucose metabolism, but showed an
      interaction with the extent of coronary narrowing.

PMID- 15948716
TI  - Carbonic anhydrase (Nce103p): an essential biosynthetic enzyme for growth of
      Saccharomyces cerevisiae at atmospheric carbon dioxide pressure.
AB  - The NCE103 gene of the yeast Saccharomyces cerevisiae encodes a CA (carbonic
      anhydrase) that catalyses the interconversion of CO2 and bicarbonate. It has
      previously been reported that nce103 null mutants require elevated CO2
      concentrations for growth in batch cultures. To discriminate between 'sparking'
      effects of CO2 and a CO2 requirement for steady-state fermentative growth, we
      switched glucose-limited anaerobic chemostat cultures of an nce103 null mutant
      from sparging with pure CO2 to sparging with nitrogen gas. This switch resulted
      in wash-out of the biomass, demonstrating that elevated CO2 concentrations are
      required even under conditions where CO2 is produced at high rates by
      fermentative sugar metabolism. Nutritional analysis of the nce103 null mutant
      demonstrated that growth on glucose under a non-CO2-enriched nitrogen atmosphere
      was possible when the culture medium was provided with L-aspartate, fatty acids,
      uracil and L-argininine. Thus the main physiological role of CA during growth of
      S. cerevisiae on glucose-ammonium salts media is the provision of inorganic
      carbon for the bicarbonate-dependent carboxylation reactions catalysed by
      pyruvate carboxylase, acetyl-CoA carboxylase and CPSase (carbamoyl-phosphate
      synthetase). To our knowledge, the present study represents the first full
      determination of the nutritional requirements of a CA-negative organism to date.

PMID- 15948718
TI  - Analysis of bone mineral density in urolithiasis patients.
AB  - BACKGROUND: The association between hypercalciuria and bone mineral density (BMD)
      has been already recognized. The aim of the present study is to relate BMD to age
      and sex and to evaluate the calcium metabolism and hypercalciuria-defined dietary
      or non-dietary category in patients with urolithiasis. METHODS: The BMI of the L2
      L4 lumbar vertebrae was measured in 310 renal stone patients (191 men and 119
      women). Percent age matched score (%AMS), which is the percent ratio of measured
      BMD to the mean BMD of age-matched control subjects, was utilized for the
      appraisal of BMD. Low BMD groups were defined by lower than 90% of %AMS. RESULTS:
      Low BMD was observed in 27.7% of urinary stone patients, which was not a
      significant difference to that of control subjects (23.5%) who were measured in
      the health examination. In male patients with urolithiasis, the frequency of
      patients in whom BMD had been apt to decrease since youth was high, but there was
      not a proven significant difference among the three age groups (20-39 years old,
      40-59 years old and 60 years old or older). In contrast, for female stone
      patients, the frequency of low BMD markedly increased in patients aged 40 years
      or older, when menopause occurs. Furthermore, in female stone patients with
      hypercalciuria, the frequency of reduced BMD reached more than 40%. When the
      cause was non-dietary hypercalciuria (classified mainly on the daily amount of
      urinary calcium excretion after ingestion of calculus test diet), the frequency
      of reduced BMD reached 65% (P < 0.01). CONCLUSIONS: In case female stone patients
      with non-dietary hypercalciuria become menopausal, not only the risk of recurrent
      lithiasis increases, but the possibility of developing osteopenia in the future
      also increases. Appropriate treatments for prophylactic effects on urolithiasis
      or osteopenia should be considered, as judged from BMD, diet, sex, urinary
      calcium excretion and other factors synthetically.

PMID- 15948717
TI  - Purification and functional characterization of aquaporin-8.
AB  - BACKGROUND INFORMATION: Aquaporins (AQPs) are a family of channels permeable to
      water and some small solutes. In mammals, 13 members (AQP0-AQP12) have been
      found. AQP8 is widely distributed in many tissues and organs. Previous studies in
      frog oocytes suggested that AQP8 was permeable to water, urea and ammonium, but
      no direct characterization had yet been reported. RESULTS: We expressed
      recombinant rAQP8, hAQP8 and mAQP8 (rat, human and mouse AQP8 respectively) in
      yeast, purified the proteins to homogeneity and reconstituted them into
      proteoliposomes. Although showing high sequence similarity, AQP8 proteins from
      the three species had to be purified with different detergents prior to
      reconstitution. In stopped-flow studies, all three AQP8 proteoliposomes showed
      water permeability, which was inhibited by mercuric chloride and rescued by 2
      mercaptoethanol. rAQP8 and hAQP8 proteoliposomes did not transport glycerol or
      urea but were permeable to formamide, which was also inhibited by mercuric
      chloride. In the oocyte transport assay, hAQP8-injected oocytes showed
      significantly higher [14C]methylammonium uptake than water-injected oocytes.
      CONCLUSIONS: In the present study, we successfully purified rAQP8, hAQP8 and
      mAQP8 proteins and characterized their biochemical and biophysical properties.
      All three AQP8 proteins transport water. rAQP8 and hAQP8 are not permeable to
      urea or glycerol. Moreover, hAQP8 is permeable to ammonium analogues (formamide
      and methylammonium). Our results suggest that AQP8 may transport ammonium in vivo
      and physiologically contribute to the acid-base equilibrium.

PMID- 15948719
TI  - Apoptosis in prostate cancer: bax correlation with stage.
AB  - BACKGROUND: Dysregulation of apoptosis may contribute to the process of prostate
      tumorigenesis by reducing the rate of cell death. Bcl-2 and bax are important
      molecules involved in the regulation of apoptosis. The aim of the present study
      is to examine apoptosis and related regulatory molecular markers in a group of
      Iranian patients with prostate cancer. METHODS: Paraffin-embedded tissues from 50
      patients of prostate carcinoma were examined for the expression of bcl-2
      antiapoptotic and bax proapoptotic markers and also proliferation marker, Ki-67,
      by immunohistochemistry. Detection of apoptotic cells was performed using TUNEL
      method. Correlation between apoptotic index, proliferation index and bcl-2 and
      bax expression with stage, pathological grade and Gleason score was determined.
      RESULTS: Apoptosis was detected in 12% of prostate cancers. No correlation was
      observed between apoptosis and differentiation status of carcinoma. Bcl-2
      expression was detected in 21 of samples. A significant correlation between bcl-2
      expression and Ki-67 staining index (r = 0.349, P = 0.012) was observed. High bax
      protein expression was shown in our study. We found a significant correlation
      between bax expression and stage of carcinoma (r = 0.388, P = 0.031), but not
      with the apoptosis index, suggesting the presence of a non-functional bax protein
      or the role of other proapoptotic molecules. CONCLUSION: The patients in the
      present study showed a different pattern of apoptosis positivity compared to
      other reports. Bax expression may be a useful marker for prognosis of prostate
      cancer.

PMID- 15948720
TI  - Determination of the relative probability for prostate cancer to avoid
      unnecessary biopsy.
AB  - BACKGROUND: To investigate whether using a new concept of relative probability
      for prostate cancer (RPpca) can increase sensitivity and specificity in detecting
      prostate cancer. METHODS: For 217 patients with total prostate-specific antigen
      (PSA) level of 4-20 ng/mL, prostate volume and free to total PSA (F/T) ratio were
      measured. From the fitted curves between positive predictive values for prostate
      cancer and age, prostate volume, total PSA or the F/T ratio, each function
      predicting prostate cancer was determined. RPpca defined by the combined
      functions of age, prostate volume, total PSA and F/T ratio was calculated for
      each individual patient. The probability of prostate cancer was also calculated,
      using logistic regression analysis (LRPpca). Receiver-operating characteristic
      analysis was performed to elucidate the areas under the curve (AUC),
      sensitivities and specificities and cutoff values of the conventional and new
      parameters. Finally, we investigated the applicability of the above parameters in
      the other patient group using a different PSA assay kit (AxSYM). RESULTS:
      Although RPpca had the largest AUC in the total PSA range of 4-20 ng/mL, it did
      not reach statistical significance between RPpca and F/T ratio or LRPpca. The
      cutoff values of F/T ratio, LRPpca and RPpca were determined as 0.15, 0.12 and
      0.20, respectively. Using these cutoff values in AxSYM data, RPpca had the
      highest sensitivity (91%) and specificity (57%). CONCLUSIONS: RPpca can provide
      more precise information to avoid unnecessary biopsy than LRPpca or F/T ratio.
      RPpca could be valuable to decide whether to perform prostate biopsy when using
      various PSA kits.

PMID- 15948721
TI  - Efficacy and morbidity of transrectal ultrasound-guided 12-core biopsy for
      detection of prostate cancer in Japanese men.
AB  - BACKGROUND: The objectives of the present study were to determine whether an
      extensive biopsy scheme contributes to enhanced detection of prostate cancer in
      Japanese men and to assess the associated pain and morbidity. METHODS: A total of
      147 patients were included in this analysis, with 12 biopsy cores being obtained
      from each patient. Standard systematic sextant biopsy at the apex, mid-prostate
      and base of the prostate gland was carried out under local anesthesia and this
      was followed by the acquisition of additional sextant cores at the same levels
      from the far lateral peripheral zone. Each patient answered a self-administered
      questionnaire on pain and morbidity during the 5 days following biopsy. RESULTS:
      Overall, 39 patients (26.5%) received a diagnosis of prostate cancer. Nine
      patients (23.1%) were positive only at the standard sextant sites, three patients
      (7.7%) were positive exclusively at the far lateral sites and the remaining 27
      patients (69.2%) were positive at both sites. Cancer was found most frequently in
      cores obtained from the apex (P = 0.009), with this trend being more evident in
      patients with abnormal rectal findings, positive sonographic findings, gland
      volume < 40 cm(3) and prostate-specific antigen density > 0.15 ng/mL/cm(3) (P <
      0.03). These findings were also true for those with a prostate-specific antigen
      range from 4.1 to 20.0 ng/mL. A gradual decrease in incidence and grade of pain,
      hematuria and rectal bleeding was observed during the first 5 days after biopsy
      (P < 0.0001). CONCLUSIONS: Using this 12-core biopsy scheme, we found cancer most
      frequently in cores taken at the level of the apex. While the extensive procedure
      only marginally enhanced overall detection of prostate cancer, it was well
      tolerated with gradually decreasing pain and morbidity over a brief postbiopsy
      period. Further efforts to optimize biopsy schemes are warranted.

PMID- 15948722
TI  - The possibility of 'de novo' cancer in the prostate.
AB  - BACKGROUND: To investigate the possibility of 'de novo' prostate cancer by
      analyzing the relationship between high grade prostatic intraepithelial neoplasia
      (HGPIN) and latent prostate cancer. MATERIALS AND METHODS: Latent prostate
      cancers found at autopsy were examined and 55 cancer foci with a poorly (Gleason
      grade 4 and 5) or moderately (Gleason grade 3) differentiated component were
      selected. The 55 foci were separated into two groups: (i) foci with either a
      poorly or moderately differentiated component only (single differentiation group,
      SDG); and (ii) mixed foci with two or more types of differentiation components
      (mixed differentiation group, MDG). High grade intraepithelial neoplasia was
      defined as positive if it was observed within 2 mm from the edge of the cancer
      focus and the relationship between HGPIN and the two groups was investigated.
      RESULTS: The MDG had 39 cancer foci (71.0%) and there were 16 in the SDG (29.0%).
      There were 31 foci that were small-volume cancers (<0.2 mL). In the MDG, 13 small
      volume cancer foci were HGPIN positive, but in the SDG, none of the small-volume
      cancers were HGPIN positive. CONCLUSIONS: Small-volume cancer foci without HGPIN
      in the SDG may be candidates for de novo prostate cancers.

PMID- 15948723
TI  - Use of a new local anesthesia--intracorpus spongiosum anesthesia--in procedures
      on anterior urethra.
AB  - BACKGROUND: Urologists often perform procedures on anterior urethra, which is one
      of the most sensitive parts in male patients. The aim of the present study was to
      determine the efficacy of intracorpus spongiosum anesthesia during procedures on
      anterior urethra in the outpatient clinic. METHODS: A dosage of 3 mL of 1%
      lidocaine was slowly injected into the glans penis of 51 male patients.
      Immediately following injection, they underwent different procedures on anterior
      urethra. The subjective experience of pain in the patients was assessed by
      questionnaire according to a pain scale. RESULTS: Forty-seven patients (92.16%,
      47/51) had zero pain and four cases (7.84%) had either minor or moderate
      discomfort, which was limited and tolerable. The anesthetic effect is immediate
      and has been very satisfactory. All the procedures (mean duration, 33 min), were
      successfully completed under the intracorpus spongiosum anesthesia. The act of
      injection into the glans caused instantaneous minor pain in 45 patients (88.23%,
      45/51), moderate pain in four patients and no pain in two patients. There were no
      serious complications with this anesthetic technique, although two cases had
      instantaneous trance during injection of lidocaine. CONCLUSIONS: Minor procedures
      on anterior urethra in an outpatient setting with intracorpus spongiosum
      anesthesia are generally painless, safe, simple, successful and inexpensive
      compared to those performed in a hospital.

PMID- 15948724
TI  - Evaluation of the effectiveness of sildenafil using questionnaire methods versus
      audio-visual sexual stimulation.
AB  - AIM: In the present study, an audio-visual sexual stimulation (AVSS) test was
      used to evaluate the effectiveness of sildenafil, and the AVSS test was
      coevaluated with the international index of erectile function (IIEF)
      questionnaire. METHODS: Forty-two patients with erectile dysfunction (ED) were
      examined (age range, 28-73 years; mean, 51.9 +/- 11.4 years). Each patient
      answered the IIEF questionnaire and underwent laboratory tests and the AVSS test
      before administration of sildenafil. The IIEF questionnaire and AVSS test (1 h
      after administration of 25 mg or 50 mg sildenafil) were re-evaluated in the
      outpatient clinic 4 weeks later. Questions 3 and 4 of the IIEF test were used to
      evaluate the effectiveness of sildenafil. Sildenafil was determined to be
      effective if each score totalled four or five after administration. RESULTS: The
      rate of effectiveness of sildenafil was 52.4%, and the mean score of the IIEF 5
      improved from 7.2 to 15.4 following treatment with sildenafil. The maximum and
      mean rigidity of the penile tip improved after the sildenafil treatment (36.1%vs
      57.7% and 14.2%vs 35.8%, respectively). The maximum and mean rigidity of the
      penile base rose (42.4%vs 57.7% and 17.9%vs 36.8, respectively). Similarly,
      following treatment with sildenafil, the penile tumescence increased from 6.6 cm
      to 7.6 cm at the penile tip and from 7.5 cm to 8.5 cm at the penile base.
      CONCLUSIONS: In some ED patients the results of the IIEF questionnaire are not
      always consistent with those of objective evaluation, including AVSS. In these
      patients, combined assessment using the IIEF and AVSS might be more useful to
      evaluate the precise effectiveness of sildenafil, rather than relying on the IIEF
      results alone.

PMID- 15948725
TI  - Wound approximation with tissue glue in circumcision.
AB  - BACKGROUND: To assess the feasibility of using tissue glue in the approximation
      of circumcision wounds in children. PATIENTS AND METHODS: A prospective
      randomized trial was carried out on 30 boys (age, 1-10 years) admitted to the
      Kahramanamaras Sutcuimam University Medical Faculty, Turkey. The results of wound
      approximation in circumcision with cyanoacrylate tissue glue and suturing with
      interrupted 5/0 plain catgut were compared. The operations were carried out by
      the same surgeon using an identical technique. The wounds were assessed 1 day, 3
      days, 1 week and 1 month postoperatively. RESULTS: There was no difference
      between the two groups in the rates of wound inflammation, infection, bleeding
      and dehiscence, although cosmetic appearance was better in the tissue glue group.
      The operation time was also shorter in this group. CONCLUSION: Using tissue glue
      for wound approximation in circumcision is a feasible alternative.

PMID- 15948726
TI  - Pelvic recurrence in stage I seminoma: a new phenomenon that questions modern
      protocols for radiotherapy and follow-up.
AB  - OBJECTIVE: To highlight the increased risk for pelvic relapse in patients with
      stage 1 seminoma treated with adjuvant radiotherapy limited to para-aortic
      template alone. PATIENTS AND METHODS: Over a four-year period, three patients
      presented with early pelvic recurrence after radical orchidectomy and adjuvant
      irradiation for stage 1 seminoma. In each case, radiotherapy had been limited to
      the para-aortic region with omission of the ipsilateral hemi pelvis. RESULTS:
      Pelvic recurrences occurred on the ipsilateral tumor side. Durable complete
      remission was achieved in each case; however, treatment was complex and there was
      associated morbidity. CONCLUSION: This significant incidence of pelvic recurrence
      questions the validity of modern radiotherapy protocol which excludes the
      ipsilateral pelvis from the radiation field.

PMID- 15948727
TI  - Synergistic effect between catechin and ciprofloxacin on chronic bacterial
      prostatitis rat model.
AB  - BACKGROUND: Chronic bacterial prostatitis (CBP) is the most common urological
      disease in adult men. Antibiotic therapy is the gold standard of treatment.
      However, long-term therapy resulted in many side-effects and bacterial
      resistance. Because of these reasons, we need new treatment modality that could
      replace traditional antibiotic therapy. Catechin, an extract of green tea, has
      antimicrobial effect against various bacteria and synergy effect to antibiotics.
      We evaluate the synergistic effects of catechin on the treatment of CBP in an
      animal model. METHODS: An experimental CBP model was induced in 70 male Wistar
      rats by instillation of 0.2 mL bacterial suspension (E-coli Z17, O2:K1:H-)
      containing 1 x 10(8) CFU/mL into the prostatic urethra. Microbiologically and
      histologically proven CBP model was demonstrated in 58.6% (41 of 70) of the rats
      after 4 weeks of bacterial instillation. The 41 rats demonstrating CBP were
      randomly divided into four groups; the control, catechin, ciprofloxacin and
      catechin with ciprofloxacin groups. All drug treatments were conducted over a
      period of 2 weeks. After treatment, the results were analyzed with
      microbiological cultures and histological findings of the prostate and urine
      samples to compare each group. RESULTS: Microbiological cultures and histological
      findings of the prostate and urine samples demonstrated reduced bacterial growth
      and improved inflammatory responses in all three experimental groups compared
      with the control group. The catechin group showed coherent trends of decrease in
      bacterial growth and improvements in prostatic inflammation compared with the
      control group, but not to a statistically significant degree (P > 0.05). However,
      the ciprofloxacin and catechin with ciprofloxacin groups showed statistically
      significant decreases in bacterial growth and improvements in prostatic
      inflammation compared with the control group (P < 0.05). The catechin with
      ciprofloxacin group showed a statistically significant decrease in bacterial
      growth and improvements in prostatic inflammation compared with the ciprofloxacin
      group (P < 0.05). CONCLUSIONS: These results suggest that catechin may be an
      effective material in CBP treatment. Particularly, combination treatment of
      catechin and ciprofloxacin has synergistic effect. Therefore, we suggest that the
      combination of catechin and ciprofloxacin may be effective in treating CBP with a
      higher success rate.

PMID- 15948728
TI  - Differently regulated androgen receptor transcriptional complex in prostate
      cancer compared with normal prostate.
AB  - BACKGROUND: The coregulators of androgen receptors (AR) influence the
      transcriptional activity of AR. In order to better understand the mechanism of
      carcinogenesis in the prostate, we investigated the relationship between AR and
      AR coregulators in the early stage of prostate cancer. METHODS: mRNA was purified
      from 15 samples of prostate cancer and normal tissue and transcribed into cDNA.
      We screened eight AR coregulators for different gene expressions in prostate
      cancer, comparing these with normal tissue by a real-time polymerase chain
      reaction Syber green method, then quantified each component of the AR
      transcriptional complex by a real-time PCR hybri-probe method. The extent of gene
      expression similarity was compared by simple Pearson correlation coefficient
      analysis between prostate cancer and normal tissue. We applied a z-test to
      calculate significant differences between r-values. RESULTS: We found that the
      gene expression level of FHL2 decreased in prostate cancer compared with that of
      normal tissue and the gene expressions of PSA, AR and SMRT were not significant.
      The correlation coefficient analysis revealed that strong associations were found
      in the pairs of AR versus SMRT, AR versus FHL2 and SMRT versus FHL2 in prostate
      cancer, whereas similarity was found only in the pair of AR versus FHL2 in normal
      tissue. No association was observed between prostate-specific antigen and other
      genes. CONCLUSION: These results demonstrate that the AR-AR coregulator
      relationship is different between prostate cancer and normal tissue, leading to
      the hypothesis that the AR transcriptional complex is regulated differently
      between prostate cancer and normal tissue.

PMID- 15948729
TI  - Antiplatelet therapy and spontaneous perirenal hematoma.
AB  - This case report clarifies an adverse reaction of antiplatelet therapy which has
      been a standard prophylactic method for patients harboring significant risks of
      thromboembolic events. A 71-year-old Japanese man who had been taking aspirin
      tablets (81 mg) for a year presented with sudden colic pain in the left flank
      region. An abdominal computed tomography scan revealed a significant perirenal
      hematoma of the left kidney. There were no pathological kidney conditions, such
      as renal tumors, calculi or vascular diseases, found by magnetic resonance
      imaging examination. After cessation of aspirin administration followed by
      conservative management, the hematoma completely disappeared 6 months later. This
      is the first documented case of spontaneous perirenal hematoma secondary to low
      dose aspirin treatment. While such unpleasant events occur extraordinarily, this
      should be noted as a severe risk of antiplatelet therapy.

PMID- 15948730
TI  - Renal cell carcinoma with solitary toe metastasis.
AB  - Solitary metastases to the small bones and/or to the soft tissue of the hands and
      feet (acrometastases) are rare. We report a case of renal cell carcinoma (RCC)
      with big toe metastasis revealed before the primary tumor became apparent. The
      best treatment for a single metastasis is always surgical excision, regardless of
      the lesion being synchronous or metachronous. The biological behavior of
      metastatic RCC is unpredictable and only early diagnosis and treatment may
      favorably affect patient survival. Thus, metastatic RCC should be included in the
      differential diagnosis of all enlarging cutaneous nodules, wherever they develop.

PMID- 15948731
TI  - Spontaneous recovery from renal infarction resulting from renal artery
      dissection.
AB  - A 31-year-old, previously normotensive healthy man developed right flank pain and
      was admitted to a medical service. Right renal infarction was suspected by
      enhanced abdominal computed tomography (CT) and arteriography. Fourteen days
      after the onset, he was transferred to the Oita University Hospital, Oita, Japan.
      Renal angiography revealed an isolated renal artery dissection causing renal
      atrophy due to main stem narrowing of the right renal artery. Renogram and renal
      scintigram with (99m)Tc-diethylene triamine pentaacetic acid revealed a
      remarkable decline in the glomerular filtration rate and almost no uptake in the
      right kidney. Four months later, in spite of our belief that functional recovery
      could not be expected, intravenous pyelography and enhanced abdominal CT scans
      revealed a functioning right kidney that had spontaneously recovered from the
      renal artery dissection through conservative management.

PMID- 15948732
TI  - Arteriovenous malformation of the urinary bladder: Treated by transurethral
      resection.
AB  - A localized arteriovenous malformation of the bladder is extremely rare. To our
      knowledge, arteriovenous malformation of the bladder has been reported in limited
      number of cases in the published literature. When arteriovenous malformation is
      suspected, an angiogram and pelvic computed tomography or magnetic resonance
      imaging is essential to delineate the extent of the disease and to plan
      appropriate therapy. Common symptoms include pain, gross hematuria and acute
      urinary retention. No well-established guidelines exist concerning their
      management. We report a case of an arteriovenous malformation of the urinary
      bladder that was successfully treated by transurethral resection.

PMID- 15948733
TI  - Colonic adenocarcinoma and stones in an Indiana pouch.
AB  - We report on a 63-year-old woman with adenocarcinoma and stones in an Indiana
      pouch. Adenocarcinoma of an Indiana pouch is extremely rare. To our knowledge,
      only four cases with adenocarcinoma in an Indiana pouch have been reported.

PMID- 15948734
TI  - Successful treatment of recurrent vesicourethral stricture after radical
      prostatectomy with holmium laser: report of three cases.
AB  - We report three cases with severe anastomotic strictures, which recurred several
      times after radical prostatectomy despite repeated treatments of urethral
      dilation, internal urethrotomy and/or transurethral resection. All three cases
      were finally treated with holmium laser successfully without any intraoperative
      or postoperative complications after repeated failures of each treatment. There
      were two specific characteristics in these three cases: the early onset of the
      stricture and the pinhole opening located on the top (12-o'clock) of the
      stricture wall.

PMID- 15948735
TI  - Isolated congenital urethrocutaneous fistula.
AB  - Congenital urethrocutaneous fistula of the male urethra is an extremely rare
      anomaly that is commonly seen in association with anorectal malformations or
      chordee. A case of congenital urethrocutaneous fistula not associated with other
      congenital anomalies is reported, discussing possible etiologies and surgical
      management.

PMID- 15948736
TI  - Congenital scaphoid megalourethra: report of two cases.
AB  - Congenital megalourethra is a rare congenital malformation of the penile urethra.
      It is defined as the diffuse dilatation of the anterior urethra due to the
      absence of development of the erectile tissue of the penis. Since the initial
      description, nearly 80 cases with megalourethra have been reported in English
      literature. Congenital megalourethra has been classified into scaphoid and
      fusiform types and is usually associated with additional urinary tract and other
      system anomalies, irrespective of its type and severity. We report two rare cases
      of scaphoid megalourethra without any associated anomaly. A 13-year-old boy and
      an 8-month-old boy were admitted to the Department of Pediatric Surgery with
      complaints of penile swelling and dysuria since birth. Physical examination and
      retrograde cystourethrogram confirmed the diagnosis of congenital scaphoid
      megalourethra. Both patients underwent a reduction urethroplasty. They did well
      postoperatively and voided with a normal stream without any abnormality of the
      penile shaft.

PMID- 15948737
TI  - Loss of testicular volume associated with intratesticular varicocele.
AB  - Intratesticular varicocele is a rare entity and its clinical significance is not
      well established. We report a case of left-sided intratesticular varicocele
      associated with a significant reduction in left testicular volume at follow up.
      This association has not been previously reported. Incidentally, our patient is
      also the youngest case reported in the literature to date.

PMID- 15948738
TI  - Inflammatory pseudotumor of the testis: a novel presentation of acute retroviral
      syndrome.
AB  - Inflammatory pseudotumors are a rare entity, the etiology of which is not well
      understood. It has been postulated that these non-neoplastic lesions are the
      result of a reaction to trauma, surgery, infection or local irritation, though in
      many cases an underlying cause is never found. In this case, a 30-year-old man
      with previously undiagnosed human immunodeficiency virus presented with a 2-week
      history of painless right testicular mass measuring 1 x 1 cm. The patient
      underwent right radical orchiectomy with histopathological analysis revealing an
      inflammatory pseudotumor of the testis. Further work up pointed to acute
      retroviral syndrome as the likely cause.

PMID- 15948740
TI  - Color Doppler sonography examination of partially obstructed kidneys associated
      with ureteropelvic junction stone before and after percutaneous
      nephrolithotripsy: preliminary report.
AB  - AIM: To evaluate resistive index (RI) changes before and after unilateral
      percutaneous nephrolithotripsy in chronic partially obstructed kidneys due to
      ureteropelvic junction (UPJ) stones. METHODS: Intrarenal RI of obstructed and
      contralateral normal kidneys of 18 patients were recorded immediately before the
      operations and at postoperative days 1, 7 and 30. Postoperative RI measurements
      were compared with baseline values for all patients without grouping and
      separately for different groups according to the preoperative RI value of the
      obstructed kidney. RESULTS: Mean age and symptom duration were 27.5 years and
      43.8 weeks, respectively. Preoperatively and at all postoperative controls,
      kidney diameters and renal parenchyma thicknesses were normal in all patients.
      Mean RI of obstructed kidneys decreased from 0.68 to 0.63 for all patients
      (P=0.032), from 0.64 to 0.63 for those with preoperative RI<0.70 (P=0.850) and
      from 0.73 to 0.62 for those with preoperative RI>or=0.70 (P=0.001). In patients
      with preoperative RI>or=0.70 in obstructed kidney, significant RI decreases were
      recorded at postoperative day 7 and RI differences between obstructed and
      contralateral kidneys disappeared after then. No difference was present pre- and
      postoperatively between the mean RI of obstructed and contralateral kidneys of
      the patients with RI<0.70. Mean RI of contralateral kidneys were normal
      preoperatively and showed no significant change postoperatively. CONCLUSIONS:
      Preoperative RI levels may indirectly reflect the presence of functionally
      significant obstruction in chronic obstructed kidneys related to UPJ stones.
      Patients with RI>or=0.70 may have a good indication for a surgical approach.
      Normalization of high RI occurs rapidly after percutaneous nephrolithotripsy.

PMID- 15948741
TI  - Hand-assisted laparoscopic and open living donor nephrectomy in Korea.
AB  - BACKGROUND: We compared the results of hand-assisted laparoscopic living donor
      nephrectomy (LLDN) and conventional open living donor nephrectomy (OLDN).
      METHODS: The clinical data on 49 hand-assisted LLDN and 21 OLDN on the left side
      performed at two institutions in Korea from January 2001 to February 2003 were
      reviewed. Demographic data of donors and recipients were similar in the two
      groups. RESULTS: There was one conversion to an open procedure due to bleeding in
      the LLDN group. The median operation times (180 min in LLDN versus 170 min in
      OLDN) and warm ischemic times (2.5 min in LLDN versus 2.0 min in OLDN) in the two
      groups were similar. The estimated mean blood loss, duration of hospital stay and
      complication rate was also similar in the two groups. The LLDN group reported
      less pain (visual analog scale) postoperatively (4.1 versus 5.3), but this was
      not significant (P=0.058). The time to oral intake in the LLDN group was
      significantly longer by an average of 1 day (P=0.001). Return to work was sooner
      in the LLDN group (4.0 weeks versus 6.0 weeks; P=0.026). The recipient graft
      function was equivalent between the two groups. Hand-assisted LLDN appears to be
      a safe and effective alternative to OLDN. CONCLUSION: Our findings suggest that
      this technique may give the ability provide grafts of similar quality to OLDN,
      while extending to the donors the advantages of a traditional LLDN procedure.

PMID- 15948742
TI  - Multi-modal treatment of primarily using continuous subcutaneous interferon-alpha
      injection in combination with surgery and/or radiotherapy.
AB  - PURPOSE: Thirty-nine renal cell carcinoma patients with bony metastasis were
      intensively treated, primarily with immunotherapy using natural type interferon
      alpha (IFN-alpha) continuous subcutaneous injection in combination with surgical
      resection and radiation therapy. Long-term survival was achieved, including three
      patients with complete response. The results of this study are presented.
      METHODS: The mode of administration of IFN-alpha was as follows: natural-type IFN
      alpha (25,000,000 IU) was dissolved in 60 mL of distilled water and administered
      via continuous subcutaneous injection (0.5 mL/h) as 'one course of the
      treatment'. Two courses of IFN-alpha therapy were given 2 weeks preoperatively,
      while 13 courses of IFN-alpha therapy were given postoperatively (one course per
      week). Thus, 15 courses of IFN-alpha therapy were administered during the trial
      period. Thereafter, IFN-alpha therapy was repeated either every week or every
      other week depending on the condition of the patient. Additionally, blood levels
      of IFN-alpha were monitored for four patients following initiation of IFN-alpha
      continuous subcutaneous injection therapy. RESULTS: Immediately after injection
      of IFN-alpha, blood levels of IFN-alpha started to rise, reaching 40.5 IU/mL on
      average at 24 h after initiation of IFN-alpha therapy. Thereafter, blood levels
      of IFN-alpha remained high and measurable blood levels of IFN-alpha were
      maintained for up to 24 h after completion of IFN-alpha injection. As a whole,
      IFN-alpha was detectable for 6-8 days and Cmax (maximum blood concentration of
      IFN) was 167 IU/mL. Thirty-nine patients with bony metastases were treated as
      follows: IFN mono-therapy (19 patients), IFN and radiation therapy (15 patients)
      and IFN and surgical resection of bony metastases (five patients). Fourteen
      patients survived and the details of these 14 patients are as follows: complete
      response in three cases, partial response in two, no change in six and
      progressive disease in three. Twenty-five patients died of renal cell carcinoma.
      The overall 5-year survival rate was 35.0%. CONCLUSIONS: These findings indicate
      that IFN-alpha continuous subcutaneous injection therapy is a useful modality for
      renal cell carcinoma patients with bony metastasis if administered in combination
      of radical nephrectomy and radiation therapy.

PMID- 15948743
TI  - Twelve-year follow up of a randomized prospective trial comparing bacillus
      Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer.
AB  - AIM: To compare bacillus Calmette-Guerin (BCG) with epirubicin in adjuvant
      therapy of superficial bladder transitional cell carcinoma, with respect to
      recurrence, progression and survival. Prognostic factors are also evaluated.
      METHODS: Between October 1991 and September 1999, all patients harboring
      superficial bladder cancers (Ta or T1) with any of the relevant criteria
      (stage>a, grade>1, size>1 cm, multiple or recurrent tumors), after complete
      transurethral resection were randomized to receive either 81 mg Connaught strain
      BCG or 50 mg epirubicin. Patients with recurrences were eligible to crossover,
      even repeatedly, until progression. Recurrence, progression and survival were
      analyzed in relation to initial treatment, patient characteristics and tumor
      characteristics. RESULTS: There were 209 patients included in the study, 149 men
      and 60 women. The mean age was 69.9 years (range, 24-92). The BCG group consisted
      of 102 patients and the epirubicin group contained 107 patients. Final analysis
      was made at a median follow up of 23, 47 and 61 months for recurrence,
      progression and survival, respectively. The 10-year Kaplan-Meier estimates for
      recurrence-free, progression-free and disease-specific survival were 61%, 78% and
      80%, respectively, for the BCG group. The corresponding figures were 32%, 74% and
      92%, respectively, for the epirubicin group. Time to recurrence differed
      significantly between two treatment groups (P=0.0004). Multiplicity increased the
      risk of recurrence, while grading influenced recurrence, progression and disease
      specific survival. CONCLUSIONS: Bacillus Calmette-Guerin prolonged time to
      recurrence when compared with epirubicin. Grading was shown to be a universal
      prognostic factor for recurrence, progression and disease specific survival.

PMID- 15948744
TI  - Long-term safety, tolerability and efficacy of extended-release tolterodine in
      the treatment of overactive bladder in Japanese patients.
AB  - AIM: To evaluate the long-term safety, tolerability and efficacy of extended
      release (ER) tolterodine in Japanese patients completing 12-week treatment in a
      randomized, double-blind trial comparing tolterodine ER 4 mg once daily,
      oxybutynin 3 mg three times daily or placebo in patients with overactive bladder.
      METHODS: Of 293 Japanese patients completing the 12-week study, 188 continued in
      the open-label trial and received tolterodine ER 4 mg once daily for 12 months,
      irrespective of previous treatment. The primary objective was to assess the
      safety of tolterodine ER for up to 52 weeks of treatment and at post-treatment
      follow-up. Secondary endpoints included changes in micturition diary variables,
      patient perception of bladder condition and urgency and treatment benefit.
      RESULTS: Overall, 77% of patients completed 12 months of open-label treatment.
      Tolterodine ER was well tolerated and the most common adverse event was dry mouth
      (33.5%). In general, there was no increase in adverse event frequency with long
      term treatment compared with short-term treatment. The efficacy of tolterodine ER
      was maintained over the 12-month period. The complete analysis showed a median
      reduction in incontinence episodes/week (-92.9%; mean reduction, -77.2%), a mean
      reduction in micturitions/24 h (-21.3%) and a mean increase in volume voided per
      micturition (19.6%). Of patients completing the 12-month study, 78.6% reported
      improvement in patient perception of bladder condition, 52.4% reported
      improvement in perception of urgency and 89.7% reported treatment benefit.
      CONCLUSIONS: Favorable safety, tolerability and efficacy of once-daily
      tolterodine ER was maintained over 12 months in a Japanese overactive bladder
      patient population.

PMID- 15948745
TI  - Anatomical and histological studies of so-called Mullerian duct cyst.
AB  - BACKGROUND: We examined so-called Mullerian duct cysts both histologically and
      immunohistochemically with anatomical observation to investigate the etiology of
      the 'Mullerian duct cyst'. METHODS: Five cystic lesions located in the prostatic
      midline were obtained from surgical specimens. A communication between the cystic
      lesion and the urethra via the utricular orifice was looked for and the specimens
      were subjected to histological and immunohistochemical testing. RESULTS: A
      communication between the cyst and the urethra was confirmed in four cases, but
      not in one case. Histological and immunohistochemical examinations of the
      epithelium lining indicated that its characteristics were identical to those of
      the prostatic utricle in all cases. CONCLUSIONS: The so-called Mullerian duct
      cyst exhibits features comparable to those previously described in the prostatic
      utricle. There is no evidence that these cystic lesions originate from the
      Mullerian duct remnant, at least in the epithelial lining. We suggest that they
      should be termed a prostatic utricular cyst or cystic dilation of the prostatic
      utricle, depending on whether an outlet to the urethra is absent or present,
      respectively.

PMID- 15948746
TI  - Fluctuation of night time frequency in patients with symptomatic nocturia.
AB  - BACKGROUND: We examined the fluctuation and causes of voiding frequency during
      the night in patients with symptomatic nocturia. MATERIALS AND METHODS: Actual
      night time frequency was recorded by 72 patients for a total of 769 nights (mean
      10.7 nights per patient) and was compared with the 'nocturia score' of the
      International Prostate Symptom Scores (I-PSS). If a patient experienced nocturnal
      frequency higher or lower than usual, he or she checked the items on a
      questionnaire considered reasons for the changes. RESULTS: For 471 nights of 769
      (61%), actual voiding frequency did not correspond with nocturia score. Patient
      by-patient fluctuation in actual voiding frequency during the night was marked.
      The most prevalent patient-reported reason for fluctuation was amount of fluid
      intake, followed by duration of time in bed, feeling colder or warmer during time
      in bed and increased difficulty going to sleep. Fatigue, difficulty going to
      sleep and salt intake could affect night time frequency positively or negatively.
      When nocturia score and total score of the I-PSS were high, the differences
      between actual nocturnal frequency and nocturia score were significantly larger
      (3 or less, 0.71; 3-4 or more, 1.05, P<0.0001 and 13 or less, 0.78; 14 or more,
      0.97; P=0.0030, respectively). Female patients tended to have nocturia scores
      differing from actual frequency of urination (1.03 versus male patients 0.84,
      P=0.0673). CONCLUSIONS: There is considerable discrepancy between the nocturia
      score of the I-PSS and actual voiding frequency, in addition to marked
      fluctuation of actual voiding frequency in symptomatic patients. Patient
      perception of fluctuation of night time frequency can provide clues to useful
      clinical education of patients regarding nocturia.

PMID- 15948747
TI  - Granulomatous prostatitis--an infrequent diagnosis.
AB  - BACKGROUND: Granulomatous prostatitis is an unusual benign inflammatory process
      of the prostate. Clinically, it mimics prostatic carcinoma, thus requiring
      pathological examination for diagnosis. MATERIALS AND METHODS: Histopathological
      records of 1353 prostate specimens received in the Department of Pathology,
      Government Medical College, Chandigarh, India, over a period of 8 years (1995
      2002) were reviewed and 20 cases of granulomatous prostatitis were retrieved.
      RESULTS: Out of 20 cases of granulomatous prostatitis, we encountered 12 cases of
      non-specific granulomatous prostatitis, two cases of xanthogranulomatous
      prostatitis, two cases of tuberculous prostatitis, two cases of malakoplakia
      prostate and one case each of granulomatous prostatitis associated with
      adenocarcinoma prostate and post-surgical palisading granuloma. The diagnosis was
      made by histopathological examination of Trucut biopsy, transuretheral resection
      of prostate chips or retropubic prostatectomy specimen. In all the cases,
      granulomatous prostatitis was an incidental finding. CONCLUSIONS: Non-specific
      granulomatous prostatitis is the most common type of granulomatous prostatitis.
      Despite tuberculosis being very common in India, granulomatous prostatitis
      associated with tuberculosis is not common. Distinction between non-specific and
      infectious granulomatous prostatitis is important for therapeutic reasons.

PMID- 15948748
TI  - The prevalence of penoscrotal abnormalities and inguinal hernia in elementary
      school boys in the west of Iran.
AB  - AIM: We designed a cross-sectional study in order to determine the prevalence of
      inguinal hernia and penoscrotal abnormalities in the Lorestan province, situated
      in the west of Iran. METHODS: We studied 3205 elementary-school boys, aged 6-12
      years, who underwent clinical examinations of the groin and genitalia in 2002.
      RESULTS: Abnormalities were detected in 213 children (6.64%). The most frequent
      anomaly was indirect inguinal hernia, seen in 78 children (2.4%). The other
      abnormalities were retractile testes in 39 boys (1.22%), undescended testes in 36
      boys (1.12%), hydrocele in 28 boys (0.87%) and hypospadiasis in 25 boys (0.78%).
      Also, three children had micropenises, two had epispadiasis and another two boys
      had varicoceles. Ambiguous genitalia and apenia were not seen in the present
      series. Most of the parents were not aware of their children's anomalies (60.1%).
      CONCLUSIONS: Education of the public and medical staff about these abnormalities
      and screening system are needed to improve the outcome.

PMID- 15948749
TI  - Evaluation of the role of varicocelectomy including external spermatic vein
      ligation in patients with scrotal pain.
AB  - OBJECTIVES: The aim of the present study was to assess and compare pre- and
      postoperative scrotal pain in patients with varicocele who underwent
      varicocelectomy with different approaches. METHODS: The study included 144
      consecutive patients with left-sided varicocele who had left scrotal pain for
      more than 3 months. All patients underwent varicocele ligation using either a
      subinguinal or inguinal approach with or without external spermatic vein
      ligation. We asked the patients to complete an 'Assessment Questionnaire for
      Scrotal Pain' both before and after the surgery. RESULTS: The surgery was
      successful in 101 (83.4%) of the 121 patients available for follow up. Seventy
      four (61.1%) patients reported the complete resolution of pain while 27 patients
      (22.3%) reported partial resolution. Symptoms worsened in a single case and pain
      persisted postoperatively in 19 cases (15.7%). There were no statistically
      significant differences in the characteristics of the pain and grade of
      varicocele between postoperative groups. A significant difference was observed in
      postoperative success between patients who had external spermatic vein ligation
      and those who did not, regardless of the surgical approach (inguinal or
      subinguinal). All patients who reported complete or partial resolution of pain
      stated that they would recommend surgery to relatives with the same problem.
      CONCLUSIONS: Varicocelectomy using either inguinal or subinguinal approaches is
      an effective and reasonable treatment option in this patient group and should
      include external spermatic vein ligation for a satisfactory outcome.

PMID- 15948750
TI  - Perivascular epithelioid cell tumor (PEComa) with perirenal manifestation.
AB  - We present the first case report documenting an 8-month post-surgical follow-up
      of an exceedingly rare perivascular epithelioid cell tumor (PEComa) with a
      perirenal location. Furthermore, prognostic parameters discussed in the
      literature are summarized and concise information regarding imaging
      characteristics on magnetic resonance imaging is provided. In conclusion, our
      report points toward PEComa as a family of very rare mesenchymal neoplasms that
      should be included into deliberations concerning the differential diagnosis of
      perirenal mass lesions.

PMID- 15948751
TI  - Mucinous cystadenoma mimicking simple renal parenchymal cyst in a horseshoe
      kidney.
AB  - We report a case of mucinous cystadenoma in a horseshoe kidney which
      radiologically resembled a simple renal cyst. In the published literature, three
      cases of mucinous cystadenoma of renal origin have been reported. Although these
      tumors are believed to originate from the renal pelvis, the cyst in the present
      case originated from renal parenchyma. The significance of this particular case
      is the radiological features, which mimic a simple renal parenchymal cyst and
      contribute to the histopathological definition of an extremely rare disease.

PMID- 15948752
TI  - Diffuse xanthogranulomatous pyelonephritis in a patient with myotonic dystrophy
      and cerebral palsy.
AB  - Xanthogranulomatous pyelonephritis (XGP), a morphological and clinical variant of
      chronic pyelonephritis, is an uncommon disease in children. It is characterized
      by the destruction of the renal parenchyma and replacement by granulomatous
      tissue containing foamy lipid-laden macrophages and is classified into diffuse
      and focal XGP. We present a case of diffuse XGP in a child with myotonic
      dystrophy complicated by cerebral palsy and discuss the importance of correct
      diagnosis and preoperative management to reduce inflammation and improve
      malnutrition associated with the disease.

PMID- 15948753
TI  - Granulocyte-colony stimulating factor producing urothelial carcinoma of renal
      pelvis.
AB  - We report a case of granulocyte-colony stimulating factor (G-CSF) producing
      urothelial carcinoma of the renal pelvis in a 39-year old man. The patient was
      admitted to Kobe University Hospital, Kobe, Japan, complaining of macrohematuria
      and a 6-month history of left abdominal swelling. Abdominal computed tomography
      showed a large mass in the left kidney and para-aortic lymph node enlargement. A
      remarkable degree of leukocytosis was detected without any acute infectious
      disease. Enzyme immunoassay of the serum demonstrated a remarkable high
      concentration of G-CSF. The patient underwent left nephroureterectomy and para
      aortic lymphadenectomy. Histochemical examination revealed urothelial carcinoma.
      Immunohistochemical staining with an anti-G-CSF antibody demonstrated G-CSF
      secreting cells. The patient died 8 weeks after the surgical operation. To our
      knowledge, this is the second case of G-CSF producing urothelial carcinoma of
      renal pelvis reported in the English literature.

PMID- 15948754
TI  - Superselective embolization of bladder arteries in the treatment of intractable
      bladder haemorrhage.
AB  - Bladder hemorrhage following radiation therapy is a serious complication in
      patients undergoing this treatment. Several methods have been proposed to control
      this particular situation; however, results have been far from satisfactory, with
      the exception of drastic measures such as hypogastric artery ligation and radical
      cystectomy. We recently used a method of superselective embolization of the
      bladder arteries which enabled us to control severe intractable bleeding in a
      patient submitted to bladder irradiation for a transitional cell infiltrating
      carcinoma. Compared to selective embolization and other methods, the advantages
      of superselective embolization are a lower recurrence rate concerning bleeding,
      fewer side-effects and the possibility of using adaptable embospheres (150-1000
      micron) which, on account of their marked plasticity, offer better occlusion of
      the vessels. For these reasons, superselective embolization of the bladder
      arteries should be considered as the treatment of choice in intractable bladder
      hemorrhage.

PMID- 15948755
TI  - Micropapillary bladder cancer.
AB  - A characteristic clinical course of a patient with micropapillary bladder cancer,
      a rare histological variant with high metastatic potential, is presented. An 80
      year-old woman had locally advanced high-grade bladder cancer with a focal
      micropapillary variant identified which was treated with intra-arterial
      chemotherapy with radiation therapy. Standard follow-ups involving cystoscopy
      with cold-cup biopsies and computed tomography could not detail the bladder
      carcinoma; however, the patient died of carcinomatosis 20 months after treatment.
      At autopsy, carcinomas proliferated under benign mucosa and infiltrated diffusely
      in the retro peritoneum. This behavior differs from the normal pattern of
      invasive transitional cell carcinoma, which usually proliferates forming a mass
      lesion. Thus, it may be difficult to detect micropapillary bladder cancer by
      computed tomography which demonstrates only increased tissue density in
      retroperitoneal fascia; therefore, care should be taken in the follow-up of
      micropapillary bladder cancer.

PMID- 15948756
TI  - Intestinal-type mucinous adenocarcinoma arising from the prostatic duct.
AB  - We present a case of mucinous adenocarcinoma of intestinal type arising from the
      prostatic duct in a 72-year-old Japanese man. The patient presented with
      macroscopic hematuria. Cystourethroscopy exhibited a mucus deposit at the 5
      o'clock position of the verumontanum portion. A transurethral biopsy specimen
      revealed mucinous adenocarcinoma. A radical retropubic prostatectomy was
      performed. In the prostatectomy specimen, the cancer lesion mainly showed
      intraductal growth in the prostatic ducts with scattered mucin lakes in the
      prostatic stroma. There were no abnormalities in the urethral epithelium. The
      cancer cells resembled the intestinal epithelium rather than either the prostatic
      duct or the acinar epithelium, which showed diffusely positive
      immunohistochemical staining for carcinoembryonic antigen, but showed negative
      staining for prostate-specific antigen. Therefore, these findings suggest
      mucinous adenocarcinoma of intestinal type arising from the prostatic duct. A
      number of cases with mucinous adenocarcinoma arising from the prostatic urethra
      resembling the present case have been reported, but this is the first known case
      of carcinoma arising from the prostatic duct.

PMID- 15948757
TI  - Successful management of inferior vena cava thrombus complicating advanced germ
      cell testicular tumor with temporary inferior vena cava filter.
AB  - We report a case of right testicular tumor with inferior vena cava (IVC)
      thrombus. Due to the risk of pulmonary embolization, a temporary IVC filter had
      been inserted during chemotherapy. There were no complications with the temporary
      IVC filter during the implantation period. The patient was safely treated with
      systemic chemotherapy using a temporary IVC filter followed by retroperitoneal
      lymph node and vena cava dissection.

PMID- 15948758
TI  - Adenomatoid tumor of the tunica albuginea.
AB  - Adenomatoid tumors are benign mesothelial tumors most commonly found in the
      paratesticular structures, especially the epididymis. Herein, we report a case of
      adenomatoid tumor originating in the tunica albuginea and mimicking an
      intratesticular neoplasm. We review the ultrasonographic presentation and
      literature regarding adenomatoid tumors originating in the tunica albuginea and
      testicular parenchyma.

PMID- 15948759
TI  - Primary testicular actinomycosis mimicking metastatic tumor.
AB  - We report a rare case of right primary testicular actinomycosis presenting as
      multiple testicular lesions mimicking a metastatic tumor in a 71-year-old patient
      with gastric adenocarcinoma. Preoperative diagnosis is difficult. The enlarged
      and inflamed testis was removed by orchiectomy and testicular actinomycosis was
      diagnosed after pathological examination. The patient had not received any
      further antibiotic prescription and there was no recurrent or other site
      involvement after orchiectomy. We illustrate this case, though it is rare, to
      alert pathologists and clinicians to the possible occurrence of primary
      testicular actinomycosis mimicking metastatic lesions in a cancer patient. To
      diagnose, extensive sampling of the tissue specimens may be needed. We also
      reviewed the published literature and found that the treatment of choice for
      testicular actinomycosis was orchiectomy. The usage of penicillin after
      orchiectomy does not seem to affect the outcomes of the disease.

PMID- 15948760
TI  - A simple new technique to prevent bleeding in transplant nephrectomy.
AB  - Renal transplantectomy is still a frequent procedure for a transplant surgeon.
      Nevertheless, it is constantly marred by complications, first of all bleeding. In
      fact, the local circumstances after the operation and the general health state of
      the uremic patients lead to a high incidence of this complication. To avoid this,
      we adopt a particular technique for renal extracapsular transplantectomy,
      performing three running sutures between the two faces of the renal capsule. This
      prevents the formation of the hematoma which is the basis of the continuous
      bleeding and following infection. We collected a series of nine patients who
      underwent transplantectomy in which we used this technique. No complications were
      noted.

PMID- 15948762
TI  - The mood spectrum: improving the diagnosis of bipolar disorder.
AB  - Although the distinction between bipolar and unipolar disorders served our field
      well in the early days of psychopharmacology, in clinical practice it is apparent
      that their phenotypes are only partially described by current diagnostic
      classification systems. A substantial body of evidence has accrued suggesting
      that clinical variability needs to be viewed in terms of a broad
      conceptualization of mood disorders and their common threshold or subthreshold
      comorbidity. The spectrum model provides a useful dimensional approach to
      psychopathology and is based on the assumption that early-onset and enduring
      symptoms shape the adult personality and establish a vulnerability to the
      subsequent development of Axis-I disorders. To obtain a clearer understanding of
      the depressive phenotype, it is pivotal that we increase our detection of
      hypomanic symptoms so that clinicians can better distinguish bipolar II disorder
      from unipolar depression. Diagnostic criteria sensitive to hypomanic symptoms
      have been identified that suggest bipolar II disorder is at least as prevalent as
      major depression. Moreover, the comorbidities of these illnesses are very
      different and alcoholism in particular appears to be a greater problem in bipolar
      II disorder than in unipolar depression. Structured clinical interviews and
      patient self-report questionnaires have also successfully identified the presence
      of hypomanic symptoms in patients with unipolar disorder and support the concept
      of a spectrum of bipolar illness. In conclusion, the importance of subthreshold
      syndromes should not be underestimated as failure to recognize bipolar spectrum
      disorder could delay treatment and worsen prognosis.

PMID- 15948763
TI  - Translating knowledge of genetics and pharmacology into improving everyday
      practice.
AB  - Bipolar disorder is associated with significant morbidity and mortality; however,
      many aspects of this disorder remain poorly understood. It is likely that rapid
      advances in molecular genetics and neuroimaging will play a major role in
      advancing our understanding of bipolar disorder in future. Molecular genetics
      studies have already identified some candidate genes; for example, the BDNF, G72
      and XBP1 genes, and chromosomal 'hot spots', which may confer a predisposition to
      development of bipolar disorder. Such advances may facilitate earlier, easier and
      more accurate diagnosis and provide novel targets for the treatment of this
      condition. Brain imaging studies using positron emission tomography and single
      photon emission computed tomography have shown that reduction in brain 5
      hydroxytryptamine type 2 (5-HT(2)) receptors may be associated with prevention of
      or relief from depressive symptoms. Similarly, other imaging studies suggest that
      increased dopamine levels in the synapse mediate the symptoms of bipolar mania
      and that reduction in dopamine transmission through reduction in dopamine
      synthesis or blockade of dopamine D(2) receptors may be associated with antimanic
      effects. The ability of atypical antipsychotics to block both 5-HT(2) and D(2)
      receptors and downregulate 5-HT(2) receptors may explain how these drugs treat
      both the depressive and manic symptoms of bipolar disorder. Although molecular
      genetics and imaging techniques are not yet used as clinical tools for bipolar
      disorder, they provide valuable data to improve the understanding of the
      pathophysiology of bipolar disorder and should lead to new treatments and
      potentially episode prevention.

PMID- 15948764
TI  - Atypical antipsychotics: newer options for mania and maintenance therapy.
AB  - Vieta E, Goikolea JM. Atypical antipsychotics: newer options for mania and
      maintenance therapy. Bipolar Disord 2005: 7 (Suppl. 4): 21-33. (c) Blackwell
      Munksgaard, 2005Atypical antipsychotics have been used to treat patients with
      schizophrenia for many years, but now there is increasing evidence of their
      utility in the treatment of bipolar disorder. In the past few years several
      atypical agents have received regulatory approval for use in bipolar mania.
      Through a review of randomized controlled trials for five commonly used atypical
      drugs, olanzapine, risperidone, quetiapine, ziprasidone and aripiprazole, this
      article evaluates their efficacy in the acute and maintenance phases of bipolar
      disorder. The evidence shows that atypical antipsychotics are effective in the
      treatment of manic symptoms, either alone or in combination with traditional mood
      stabilizers such as lithium and divalproex. Although emerging data indicate that
      atypical antipsychotics will be a promising addition to those therapies that are
      currently available for managing patients during the maintenance phase of bipolar
      illness, their potential in the long-term management of bipolar disorder remains
      to be fully explored. Atypical antipsychotics appear to have broadly similar
      efficacy against manic symptoms of bipolar disorder, but there are important
      differences in their tolerability profiles, which are likely to be of particular
      relevance during long-term treatment. A brief assessment of tolerability issues
      surrounding the use of atypical agents in bipolar disorder and other aspects of
      treatment that have impact on the clinical effectiveness of the therapy are
      considered.

PMID- 15948765
TI  - Bipolar depression: a new role for atypical antipsychotics?
AB  - Bipolar depression, the most common phase of bipolar disorder, causes significant
      morbidity and mortality. Traditional drugs such as lithium, lamotrigine or
      antidepressants each offer some clinical efficacy; however, efficacy can be
      limited and side effects are sometimes problematic. Thus there is a major unmet
      need for effective, well-tolerated agents for the treatment of bipolar
      depression. The atypical antipsychotics, with their proven efficacy against manic
      symptoms, are emerging as candidates for use against the depressive phase of
      bipolar disorder. Several studies have shown that some atypicals improve
      depressive symptoms in mixed episodes in patients with bipolar disorder; however,
      few studies have been performed in patients specifically with bipolar depressive
      episodes. In a randomized, placebo-controlled trial in patients with acute
      bipolar I depression, olanzapine monotherapy and an olanzapine-fluoxetine
      combination significantly improved Montgomery-Asberg Depression Rating Scale
      (MADRS) total scores compared with placebo (p < 0.001) with corresponding effect
      sizes (improvement of active treatment over placebo divided by pooled standard
      deviation) of 0.32 and 0.68, respectively. Importantly, there were no significant
      differences in rates of switch into mania among the three groups. Recent results
      from an 8-week, randomized placebo-controlled trial in patients with bipolar I
      and II disorder who were experiencing a bipolar depressive episode showed that
      quetiapine (300 and 600 mg/day) had significantly greater efficacy compared with
      placebo in improving the core symptoms of depression, including suicidal
      thoughts. Quetiapine significantly improved MADRS total scores compared with
      placebo (p < 0.001); effect sizes (improvement of quetiapine over placebo divided
      by pooled standard deviation) of 0.66 and 0.80 for 300 and 600 mg/day quetiapine,
      respectively, were observed. Both doses of quetiapine significantly improved
      symptoms of anxiety, sleep quality and global quality of life (all, p < 0.001
      versus placebo). These initial findings suggest that atypical antipsychotics may
      prove to be important future treatments for patients with bipolar depression.

PMID- 15948766
TI  - The factor V Leiden and the G20210A prothrombin gene mutations are rare in women
      with fetal death.
AB  - PROBLEM: To determine if there is an association between two commonly inherited
      thrombophilias, the factor V Leiden and the G20210A prothrombin mutations, and
      fetal death. METHOD OF STUDY: We used a case-control study design to compare the
      frequencies of these mutations in women with fetal death and controls. Fetal
      death was the intrauterine death of the conceptus > or =10 weeks gestation.
      Controls had one live birth, no miscarriages, and no fetal death. Results were
      compared using chi square analysis. RESULTS: One hundred and seventy-five cases
      and controls were identified. There were 4.6% of cases and 3.8% of controls
      heterozygous for the factor V Leiden mutation (NS), and 1.3% of cases and 1.7% of
      controls heterozygous for the prothrombin mutation (NS). CONCLUSION: In our
      population, neither the factor V Leiden nor the G20210A prothrombin mutations are
      associated with fetal death. Further evidence is required before routine
      screening for these mutations can be recommended.

PMID- 15948767
TI  - Human endometrial epithelial cells (EEC) constitutively express more
      intercellular adhesion molecule (ICAM)-1 than endometrial stromal cells (ESC) in
      culture.
AB  - PROBLEM: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an
      important role in pathophysiological processes in endometrial tissue. The aim of
      this study was to quantify and compare the expression of ICAM-1 mRNA and protein
      in cultured endometrial epithelial cells (EEC) versus endometrial stromal cells
      (ESC). METHOD OF STUDY: EEC and ESC were isolated from human endometrium and
      cultured. At confluency, ICAM-1 mRNA was measured by real-time reverse
      transcriptase-polymerase chain reaction, the membrane-bound form (mICAM-1) by
      immunocytodensitometry, and the soluble form (sICAM-1) by enzyme-linked
      immunosorbent assay. RESULTS: At the transcriptional level, we observed a 1.7
      fold increase in ICAM-1 expression in EEC versus ESC. mICAM-1 immunostaining in
      EEC [cell-relative membrane-bound signal-specific optical density (CR-M-SOD):
      0.056 +/- 0.05] was stronger (P < 0.05) than in ESC (CR-M-SOD: 0.009 +/- 0.07).
      EEC were found to secrete more (P < 0.01) sICAM-1 ([sICAM-1] = 15.59 +/- 2.96
      ng/mL) than ESC ([sICAM-1] = 5.14 +/- 2.61 ng/mL). CONCLUSIONS: Cultured EEC
      constitutively express significantly more ICAM-1 mRNA and protein than ESC.

PMID- 15948768
TI  - Antisperm antibodies in semen, sera and follicular fluids of infertile patients:
      relation to reproductive outcome after in vitro fertilization.
AB  - PROBLEM: Data given in the literature, regarding the influence of antisperm
      antibodies (ASA) in the semen and/or sera on in vitro fertilization (IVF)
      procedure outcome are controversial. The aim of this study was to compare the
      prevalence of ASA in semen, peripheral blood and follicular fluid as well as to
      determine total immunoglobulin concentration in the serum and follicular fluid.
      Selected parameters were analyzed with regard to IVF outcome. METHOD OF STUDY:
      The study enrolled 52 married couples. ASA in the semen was determined by direct
      immunobead mixed antiglobulin reaction (MAR Screen test), while in the peripheral
      blood and follicular fluid was determined by indirect immunobead MAR Screen test.
      Immunoglobulin (IgG, IgM and IgA) concentration in the follicular fluid and serum
      was determined by a liquid-phase immunoprecipitation assay with nephelometric end
      point detection and analyzed with regard to IVF outcome. RESULTS: Semen MAR test
      IgG was < 20% in 38 couples, and > 20% in 14 couples. Fertilization (73.2% versus
      71.5%) and pregnancy rates (28.9% versus 28.57%) in both groups of patients were
      not significantly different. The results of direct and indirect MAR test were not
      associated with fertilization and pregnancy rates. Total serum IgG, IgM and IgA
      in infertile women were within normal ranges. Follicular fluid IgG was within
      normal values for serum samples, while IgA and IgM were decreased. CONCLUSION:
      The presence of ASA on sperm or in the serum and follicular fluid was not
      associated with IVF outcome in the couples with good quality semen
      characteristic.

PMID- 15948769
TI  - Cytokine profile of natural killer cells in early human pregnancy.
AB  - PROBLEM: To examine whether the NK1/NK2/NK3/NKr1 paradigm can be adapted in
      natural killer (NK) cells. METHOD OF STUDY: Mononuclear cells were isolated from
      peripheral blood and/or decidua in healthy non-pregnant women (n = 17), early
      pregnant women (6-12 weeks of gestation, n = 17) and miscarriage cases (6-11
      weeks of gestation, n = 10). We investigated the production of transforming
      growth factor (TGF)-beta, interleukin (IL)-4, IL-5, IL-10, IL-13, interferon
      (IFN)-gamma and tumor necrosis factor-alpha from peripheral blood- and decidual
      CD56bright NK cells and -CD56dim NK cells by flow cytometry. RESULTS: In the
      peripheral blood of the non-pregnant subjects, the main populations of CD56bright
      NK cells and CD56dim NK cells were IFN-gamma-producing NK1 type cells.
      Populations of IL-10-producing NKr1 type cells in peripheral blood CD56bright NK
      cells and CD56dim NK cells in early pregnant women were significantly greater
      compared with those in non-pregnant women, and these cells population decreased
      in miscarriage cases. In the early pregnancy decidua, the main populations of
      CD56bright NK cells and CD56dim NK cells were TGF-beta-producing NK3 type cells,
      and NK1 type cells were rare. NK3 type cells in decidua were significantly
      decreased in miscarriage cases compared with those in normal pregnant subjects.
      IL-4-, IL-5- or IL-13-producing NK2 type cells were rare in peripheral blood and
      decidua. CONCLUSION: These data support the NK1/NK2/NK3/NKr1 hypothesis. NKr1
      type cells in peripheral blood and NK3 type cells in decidua might play some
      important roles in the maintenance of pregnancy by regulation of maternal immune
      function.

PMID- 15948770
TI  - Maternal cytokine production patterns in women with pre-eclampsia.
AB  - PROBLEM: To determine the levels of cytokines produced upon mitogenic or
      antigenic stimulation of maternal peripheral blood mononuclear cells (PBMC) from
      women with pre-eclampsia. METHOD OF STUDY: PBMC from 54 women with a history of
      successful pregnancy and 32 women undergoing pre-eclamptic delivery were
      stimulated with a mitogen or with autologous placental cells or with trophoblast
      antigens, and the levels of cytokines released into the culture supernatants then
      assessed by enzyme-linked immunosorbent assay. RESULTS: Significantly higher
      levels of the Th1 cytokines, interferon-gamma, and tumor necrosis factor-alpha
      were produced by the pre-eclamptic group than by the normal pregnancy group,
      which on the contrary showed significantly greater production of the Th2
      cytokines, interleukin (IL)-4, IL-5, IL-6 and IL-10. A comparison of the ratios
      of Th2 to Th1 cytokines indicates a higher Th1 cytokine bias in pre-eclampsia as
      compared with normal pregnancy. CONCLUSIONS: These data are suggestive of a
      maternal pro-inflammatory cytokine bias in pre-eclampsia.

PMID- 15948771
TI  - Delineation of regions in the extracellular domain of follicle-stimulating
      hormone receptor involved in hormone binding and signal transduction.
AB  - PROBLEM: To use antipeptide antibodies to potential surface-oriented regions of
      the extracellular domain (ECD) of the human follicle-stimulating hormone receptor
      (hFSHR) to delineate regions involved in FSH binding and FSH-induced signal
      transduction. METHOD OF STUDY: We developed and characterized antipeptide
      antibodies to different, potentially surface-oriented regions of the ECD of
      hFSHR. The ability of these antibodies to recognize the receptor was studied by
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western
      blotting. The ability to modulate FSH binding and cAMP generation was studied by
      the radioreceptor assay and in vitro FSH bioassay respectively. RESULTS:
      Antipeptide antibodies to regions 15-31, 216-235, 285-300 and 327-341 hFSHR
      inhibited both FSH binding and cAMP production. Regions 15-31 and 216-235 were
      accessible to their cognate antipeptide antibodies both before and after FSH
      binding, while regions 285-300 and 327-341 hFSHR were accessible only prior to
      FSH binding. CONCLUSIONS: Based on the observations made with respect to
      accessibility to antipeptide antibodies, ability of antibodies to inhibit FSH
      binding and the subsequent cAMP generation and kinetics of antibody binding,
      regions 285-300 and 327-341 hFSHR appear to be the chief FSH-binding sites, while
      regions 15-31 and 216-235 hFSHR serve as ancillary FSH-binding sites.

PMID- 15948772
TI  - Poly I-C induces early embryo loss in f344 rats: a potential role for NK cells.
AB  - PROBLEM: Natural killer (NK) cells were associated with first trimester embryo
      loss. The current study in the inbred F344 rat assessed the role of NK cells in
      mediating resorptions caused by poly I-C, a non-specific immunostimulator. METHOD
      OF STUDY: On fifth day of gestation, rats were injected intraperitoneally with
      anti-NKR-P1 (1.5 mg/kg, i.p.) to deplete NK cells, and with mouse serum or saline
      to control for non-specific effects. Poly I-C (4 mg/kg, i.p.) or vehicle were
      administered 2 days later. Resorptions were assessed on day 13.5. RESULTS: Poly I
      C significantly elevated resorption rates, and anti-NKR-P1 abolished this effect.
      Body weight was reduced in all rats treated with poly I-C, including NK-depleted
      rats. This indicates the ability of NK-depleted rats to respond to poly I-C, yet
      to refrain from the resorption-promoting effects of poly I-C. CONCLUSIONS: This
      study suggests a role for NK cells in mediating poly I-C-induced resorptions.

PMID- 15948774
TI  - Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and
      safety of mometasone furoate.
AB  - Mometasone furoate nasal spray (MFNS; Nasonex, Schering-Plough Corporation,
      Kenilworth, NJ, USA) is an effective and well-tolerated intranasal corticosteroid
      approved for the prophylactic treatment of seasonal allergic rhinitis, and the
      treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid
      onset of action and excellent safety and efficacy profiles. Having recently
      received approval for the treatment of nasal polyposis, data indicate that MFNS
      may also be effective in rhinosinusitis.

PMID- 15948776
TI  - Scientific contributions and citations.

PMID- 15948777
TI  - Nordic research in ophthalmology.
AB  - Nordic ophthalmologists and vision scientists are active in many fields of eye
      research. This is most evident at the biannual Nordic Congress of Ophthalmology,
      most recently held in Malmo in June 2004. The authors here review some of the
      research in vision and ophthalmology presented at this meeting or published
      recently by Nordic scientists. This paper does not represent a comprehensive
      review of all Nordic research in the field, but attempts to give an overview of
      some of the activities underway in eye research in this part of the world.

PMID- 15948778
TI  - Duration of face-down positioning after macular hole surgery: a comparison
      between 1 week and 3 days.
AB  - PURPOSE: To investigate whether shortening the duration of face-down positioning
      from 1 week to 3 days affects the anatomical success rate of macular hole
      surgery. METHODS: A total of 53 consecutive eyes in 50 patients with full
      thickness macular holes of 2-24 months' (average 10 months) duration were
      included in the study. In 20 eyes (37.7%) the hole had been present for more than
      1 year. All patients were operated with vitrectomy, removal of the posterior
      hyaloid and a complete fluid-gas exchange. Peeling of the internal limiting
      membrane (ILM) was not performed. Postoperatively, the duration of face-down
      positioning differed between two consecutive groups of patients. The first group
      (29 patients) was instructed to keep their heads face-down for 7 days, while the
      second group (24 patients) maintained face-down positioning for only 3 days.
      RESULTS: Overall, 90.6% of the macular holes closed with one operation. The
      macular hole closed successfully in 27 (93.1%) of the 29 eyes in the 1-week group
      and in 21 (87.5%) of the 24 eyes in the 3-day group (p > 0.05). CONCLUSION:
      Although the frequency of hole closure differed slightly in the two study groups,
      the difference was far from statistically significant. Thus, the results indicate
      that 3 days of strict face-down positioning are sufficient to achieve closure of
      even longstanding macular holes without removal of the ILM.

PMID- 15948779
TI  - Functional and anatomic outcome of scleral buckling versus primary vitrectomy in
      pseudophakic retinal detachment.
AB  - PURPOSE: To conduct a randomized prospective clinical trial to compare primary
      vitrectomy without scleral buckling versus conventional scleral buckling surgery
      in pseudophakic primary retinal detachment (PPRD) in terms of anatomic attachment
      rate, functional outcome and complications. METHODS: Fifty consecutive eyes of 50
      patients with PPRD were randomized into two groups, with 25 patients in each of
      group 1 (scleral buckling group) and group 2 (pars plana vitrectomy without
      buckling group) in a hospital setting and followed up at 1 week, 2 weeks, 6 weeks
      and 6 months. RESULTS: A primary reattachment rate of 76% (19 retinas) was
      obtained in group 1, while a reattachment rate of 84% (21 retinas) was achieved
      in group 2. The final anatomic reattachment rate was 100% in both groups. The
      causes of failure in group 1 were proliferative vitreoretinopathy in five eyes
      and open break/missed break in one eye. The causes of failure in group 2 were
      missed break/open break in three eyes and proliferative vitreoretinopathy in one
      eye. Best corrected visual acuity (BCVA) at 2 weeks was better in group 1, while
      the final BCVA at end of 6 months was two lines better in group 2. The mean
      change in refractive error was -- 1.38 D in group 1 and -- 0.85 D in group 2.
      CONCLUSIONS: Pars plana vitrectomy without buckling provides an effective
      treatment for PPRD and results in better longterm visual and anatomic outcomes
      than conventional scleral buckling.

PMID- 15948780
TI  - The cut-and-paste method for primary pterygium surgery: long-term follow-up.
AB  - OBJECTIVE: To evaluate the recurrence rate, reoperation rate and side-effects of
      a novel technique for pterygium surgery. DESIGN: Retrospective study.
      PARTICIPANTS: The study included 461 eyes of 381 patients operated for primary
      nasal pterygium by the same surgeon between 1994 and 2003 and followed for 23 +/-
      20 months (range 6-112 months). METHODS: Autologous conjunctival grafts harvested
      at the superotemporal limbus were used to cover the sclera after pterygium
      excision. Using a retrospective chart review, the outcome after attaching the
      transplant to the sclera with a fibrin tissue adhesive (n = 325) was compared to
      the outcome after graft attachment using absorbable sutures (n = 136). MAIN
      OUTCOME MEASURES: Recurrence rate, reoperation rate and complications. RESULTS:
      The recurrence rate was 5.3% in the glue group and 13.5% in the suture group (p =
      0.01). The reoperation rates were 1.2% and 3.3%, respectively (p = 0.31).
      Complications, such as transient transplant oedema and persistent corneal
      epithelial defects, occurred equally in both groups. CONCLUSION: Using a fibrin
      tissue adhesive instead of sutures when attaching the conjunctival transplant in
      primary pterygium surgery results in a significantly lower recurrence rate.

PMID- 15948781
TI  - Placing the Molteno implant in a long scleral tunnel to prevent postoperative
      tube exposure.
AB  - PURPOSE: The purpose of this study was to retrospectively evaluate whether it is
      possible to decrease the risk of Molteno tube erosion through the conjunctiva by
      using a new technique where the silicone tube is inserted into a scleral tunnel
      instead of being covered only by the conjunctiva. METHODS: We reviewed Molteno
      implants carried out at the University Hospital of Oulu, in 332 patients who
      underwent traditional Molteno implantation between October 1986 and October 1998
      and 92 patients who underwent surgery with the new technique between November
      1998 and April 2001. RESULTS: With our former technique, conjunctival erosions
      occurred in 15 eyes of 15 patients (4.5%) after a median follow-up of 3.5 months
      (range 1-72 months); no conjunctival complications were discovered in patients
      who underwent surgery using the new technique during a median follow-up of 22
      months (range 10-39 months). (p = 0.038, two-sample test of proportions).
      CONCLUSION: Inserting the Molteno tube into a scleral tunnel prevents tube
      extrusion through the conjunctiva in eyes with Molteno implants. The technique
      for making the scleral tunnel is described.

PMID- 15948782
TI  - Clinical evaluation of the arched blade for cataract surgery.
AB  - PURPOSE: To evaluate the efficacy of the arched blade for making clear corneal
      incisions in cataract surgery. METHODS: This prospective study comprised 112 eyes
      of 74 patients scheduled for cataract surgery. Temporal clear corneal incisions
      were made with either a 3.2-mm conventional flat blade or the arched blade. The
      choice of knife was randomly assigned. Two surgeons, one with substantial
      cataract surgery experience and the other with less experience, performed the
      surgery. Corneal topography and aberration were examined pre- and
      postoperatively. The degree of surgically induced astigmatism (SIA) and high
      order aberration was analysed. The self-sealing ability of the wound was also
      compared between both blades. RESULTS: For the less experienced surgeon, the
      degree of SIA was significantly higher with the 3.2-mm flat blade than with the
      3.2-mm arched blade as measured at any time during postoperative follow-up. For
      the more experienced surgeon, the degree of high order aberration increased
      significantly with the 3.2-mm flat blade. The incision's self-sealing ability was
      significantly better when the wound was made with the arched blade rather than
      with the flat blade. CONCLUSION: The arched blade proved to be effective in
      reducing surgically induced astigmatism and high order aberration in cataract
      surgery, particularly when used by the less experienced surgeon. Using the arched
      blade should lead to better wound self-sealing and, therefore, safer surgical
      results.

PMID- 15948783
TI  - Intraocular lens power prediction for triple procedures in Fuchs' dystrophy using
      multiple regression analysis.
AB  - PURPOSE: To develop a correcting term for intraocular power (IOLP) prediction for
      penetrating keratoplasty combined with simultaneous extracapsular cataract
      extraction and posterior chamber lens implantation (triple procedure). METHODS:
      As part of a prospective clinical study, triple procedures were performed in 42
      eyes with Fuchs' dystrophy. Only eyes with readable preoperative K-values were
      included in this study. Differences (DEV) between achieved and target refraction
      (TR) depending on the values of the theoretical-optical formula according to
      HAIGIS were investigated using multiple regression analysis in a linear anova
      model: DEV = a + b CP + c AL + d IOLP + e TR. CP represents central corneal
      power, AL represents axial length. RESULTS: Spherical equivalent after suture
      removal was - 1.39 +/- 2.86 D (TR: - 1.64 +/- 1.72 D). A multiple regression
      formula was developed for correction of conventionally calculated IOL power. CP
      (b = - 1.391, p = 0.028), AL (c = - 4.733, p = 0.007), IOLP (d = - 1.301, p =
      0.009) and TR (e = - 1.804, p = 0.005) correlated significantly with DEV (a =
      198.684). CONCLUSION: Proposed correcting multiple regression formula for IOL
      power prediction may help to improve the postoperative refractive outcome in
      patients undergoing triple procedures.

PMID- 15948784
TI  - Photocoagulation for diabetic retinopathy: determinants of patient satisfaction
      and the patient-provider relationship.
AB  - PURPOSE: To assess satisfaction with photocoagulation treatment in diabetes
      patients and to investigate how it relates to patient-related characteristics and
      patients' visual ability. Further, to observe the interaction between physician
      and patient and suggest ways to improve the patient-provider relationship and,
      thereby, treatment satisfaction. METHODS: This open longitudinal study included
      123 diabetes patients undergoing first photocoagulation treatment for diabetic
      maculopathy or proliferative retinopathy. The Diabetes Treatment Satisfaction
      Questionnaire (DTSQ) was completed by all patients. Communication, scheduling and
      adherence scores were defined for each physician-patient pair. Outcome measures
      were: the patient's overall satisfaction with laser treatment; the patient's
      degree of satisfaction in relation to visual results; communication, scheduling
      and adherence scores, and visual acuity results. RESULTS: The level of
      satisfaction after initial photocoagulation treatment was high; 46.4% of patients
      with proliferative retinopathy and 53.1% with maculopathy scored 31 or higher.
      Although 69.5% of all patients reported that their expectations of treatment
      corresponded to their final 9-month visual results, only 8.7% of these patients
      reported an improvement in visual acuity after 9 months. The number of unwanted
      actions performed by the patients during treatment were significantly related to
      the number of unclear instructions given by the physician (Fisher's exact test P
      < 0.01). CONCLUSIONS: A high level of satisfaction was observed, despite the
      minimal improvements in visual acuity. Attempts to further improve patient
      satisfaction might focus on improved education of patients on the possible
      benefits of laser treatment, greater care in communicating information during
      treatment, additional nursing support, and additional clerical time to
      communicate with patients before each appointment.

PMID- 15948785
TI  - Correlation between optic disc topography and retinal nerve fibre layer
      measurements in glaucoma.
AB  - PURPOSE: To test the correlation between optic disc topography (as measured by
      confocal scanning laser ophthalmoscopy [CSLO]) and retinal nerve fibre layer
      (RNFL) measurements (as measured by scanning laser polarimetry [SLP]) in
      glaucoma. MATERIAL AND METHODS: A total of 112 patients with primary open-angle
      glaucoma and 88 normal individuals were enrolled in the study. All individuals
      underwent a thorough ophthalmic evaluation, a 24-2 full threshold Humphrey visual
      field, SLP with the GDx (Version 1.0.12) and CSLO with the TOPSS. Receiver
      operator characteristic curves were created for each individual CSLO and SLP
      parameter. Linear correlations between the four best parameters from each device
      were calculated. Finally, linear correlations between the same variables,
      controlled for the severity of visual field damage, were calculated. RESULTS: The
      best individual parameters in the diagnosis of glaucoma for each device were cup
      area, vertical cup : disc ratio, cup : disc area ratio and average cup depth for
      CSLO, and the Number, maximum modulation, ellipse modulation and superior nasal
      for SLP. Moderate to strong correlations were observed in 62% of the pairs.
      However, only 6% and 12% of the correlations remained moderate when we controlled
      for the visual field mean deviation and correct pattern standard deviation,
      respectively. CONCLUSIONS: The correlation between optic disc topography and RNFL
      measurements in glaucoma patients is moderate and highly dependent on the level
      of visual field loss.

PMID- 15948786
TI  - Random measurement error in visual acuity measurement in clinical settings.
AB  - PURPOSE: To estimate the random measurement error in visual acuity (VA)
      determination in the clinical environment in cataractous, pseudophakic and
      healthy eyes. METHODS: The VAs of patients referred for cataract surgery or
      consultation by ophthalmic professionals were re-examined and the VA results for
      distance using projector acuity charts were compared. Refractive errors were also
      remeasured. A total of 99 eyes (41 cataractous, 36 pseudophakic and 22 healthy
      eyes) were examined. The healthy comparison group consisted of hospital staff.
      Only one eye of each person and eyes with Snellen VAs of 0.3-1.3 (logMAR 0.52 to 
      0.11) were included. The mean time interval between the first and second
      examinations was 45 days. RESULTS: The estimated standard deviation of
      measurement error (SDME) of repeated VA measurements of all eyes was logMAR 0.06.
      Eyes with the lowest VA (0.3-0.45) had the largest variability (SDME logMAR
      0.09), and eyes with VA > or = 0.7 had the smallest (SDME logMAR 0.04). The
      variability may be partly explained by the line size progression in lower VAs,
      partly by the difference in the remeasurement of the refractive error. The
      difference in the average VA between examinations 1 and 2 (logMAR 0.15 versus
      0.12) was considered to be of some interest because it indicates that some
      learning effect is possible. CONCLUSION: Visual acuity results in clinical
      settings have a certain degree of inherent variability. In this series
      variability ranged from SDME logMAR 0.04 (eyes with good vision) to logMAR 0.09
      (in the lower vision group) in the Snellen VA range of 0.3-1.3. Changes should be
      judged with caution, especially in cases of decreased VA.

PMID- 15948787
TI  - The time pattern of bilateral exudative age-related macular degeneration.
AB  - PURPOSE: To study time patterns in bilateral exudative age-related macular
      degeneration (AMD) and the pattern of drusen before and after the onset of
      exudative AMD. MATERIAL AND METHODS: Out of 2220 individuals in the Icelandic
      genetic study of AMD, 151 had bilateral exudative AMD. We searched for previous
      records in the Icelandic University Retina Unit. For the 65 patients with a
      fluorescein angiography record of both eyes, we established the time between the
      onset of disease in each eye. For the 53 patients with colour fundus photographs
      of the latter eye taken prior to the occurrence of exudative disease, we graded
      the drusen before and after the onset of exudative AMD in the second eye.
      RESULTS: The time interval between the onset of exudative AMD in the first and
      second eyes was 2.5 years (95% CI: 1.8-3.2; n = 65) and the median was 1.8 years.
      In 82% of cases the second eye was affected within 4 years. Soft drusen in the
      macula were found in 95% of eyes that later developed exudative disease (n = 53).
      Soft and hard drusen decreased in number in the central macula following the
      development of exudative disease. CONCLUSIONS: Bilateral exudative AMD develops
      within a few years in both eyes. Drusen are less visible following the onset of
      exudative AMD in the second eye.

PMID- 15948788
TI  - Dominant optic atrophy: correlation between clinical and molecular genetic
      studies.
AB  - PURPOSE: To assess the clinical picture and molecular genetics of 14 Finnish
      families with dominant optic atrophy (DOA). METHODS: The clinical status of
      family members was based on the assessment of visual acuity, colour vision,
      visual fields and optic nerve appearance; 31 individuals were affected, two
      suspect and 21 unaffected. A total of 30 coding exons and exon- intron boundaries
      of the OPA1 gene were sequenced in order to detect mutations. RESULTS: Half the
      patients were diagnosed at the age of < or = 20 years. Ten out of 20 affected
      individuals followed up for > or = 6 years had a progressive disease and 10 had a
      stable disease. According to WHO criteria, 36% of the affected patients were
      visually handicapped. Eight OPA1 pathogenic mutations, all but one novel, and 18
      neutral polymorphisms were detected. CONCLUSION: The most sensitive indicators of
      DOA were optic disc pallor and dyschromatopsia. With molecular genetic analysis,
      asymptomatic mutation carriers and DOA cases with a mild clinical outcome were
      ascertained. No mutational hotspot or Finnish major mutation in the OPA1 gene
      could be demonstrated as most families carried a unique mutation. No obvious
      genotype- phenotype correlation could be detected. Detailed clinical assessment
      and exclusion of non-DOA families prior to mutation screening are necessary for
      obtaining a high mutation detection rate.

PMID- 15948789
TI  - Echographic examination with new generation contrast agent of choroidal malignant
      melanomas.
AB  - PURPOSE: To determine the efficacy of echography with new generation contrast
      agents in visualizing vascularization of choroidal malignant melanomas. METHODS:
      An echographic contrast medium consisting of phospholipidic microbubbles filled
      with sulphur hexafluoride (Sonovue) was used to visualize microcirculation in 25
      cases of choroidal lesions already diagnosed with standardized echography (21
      choroidal malignant melanomas, four disciform lesions). RESULTS: In untreated
      malignant melanomas contrast agent echography revealed the presence of a dense
      microcirculation inside the mass. In one case vitreal seeding of the contrast
      agent was detectable before enucleation and histological examination revealed the
      presence of tumoral cells. In 12 cases treated with transpupillary thermotherapy,
      contrast agent echographic evaluation showed heavy regression of microcirculation
      after 1 week, confirmed in one case by histology, and a reduction of 70-80% in
      dimensions after 6 months (which appeared to have stabilized at subsequent
      examinations). In four cases treated with proton beam brachytherapy 2 years prior
      to our examination, contrast agent echography showed the absence of a
      microvascular network and the presence of large vessels and blood lakes. In four
      cases of disciform lesion, deep and superficial retina-associated vascularization
      was observed, with a weak spread of contrast agent inside the lesion. CONCLUSION:
      Live representation with good resolution of choroidal malignant melanoma
      microcirculation was obtained.

PMID- 15948790
TI  - The effects of sildenafil on ocular blood flow.
AB  - PURPOSE: To investigate the effects of sildenafil, a popular new drug in the
      treatment of erectile dysfunction, on ocular blood flow. METHODS: This study was
      designed as a prospective, double-blind, placebo-controlled study. Twenty
      participants with erectile dysfunction were given a single oral dose of 100 mg
      sildenafil, while 10 participants with erectile dysfunction were given placebo.
      All the participants underwent routine systemic and ophthalmological
      examinations. Intraocular pressure, systolic and diastolic blood pressure and
      ocular blood flow (ophthalmic, central retinal, short posterior ciliary arteries)
      were measured in both eyes before and 1 hour after the dose of sildenafil or
      placebo. Ocular blood flow measurements were performed using colour Doppler
      ultrasonography. RESULTS: None of the parameters were significantly different
      between the groups before study drug intake. Although central retinal artery
      velocities were not changed, ophthalmic artery and short posterior ciliary artery
      peak systolic velocity, end-diastolic velocity, and mean velocity values were
      significantly increased 1 hour after drug intake in the sildenafil group compared
      to the placebo group (p < 0.05). CONCLUSION: Sildenafil causes a significant
      increase in blood flow in these arteries. A possible role of inhibition of
      phosphodiesterase-5 in vascular smooth muscles by sildenafil is implicated.
      Further studies are needed to investigate the effects of sildenafil on ocular
      blood flow in patients with senile macular degeneration, diabetic retinopathy and
      glaucoma.

PMID- 15948791
TI  - Reduction of conjunctival bacterial flora by povidone-iodine, ofloxacin and
      chlorhexidine in an outpatient setting.
AB  - PURPOSE: To compare the reduction of conjunctival bacterial flora by povidone
      iodine 4%, ofloxacin 0.3%, and chlorhexidine 0.05% for endophthalmitis
      prophylaxis before corneal suture removal in an outpatient setting. METHODS: In
      each group of 25 consecutive subjects who presented for outpatient ophthalmic
      evaluation, one eye was treated with either povidone-iodine 4% (PI), ofloxacin
      0.3% (Oflox) or chlorhexidine 0.05% (Chex). The other eye served as a control.
      Three minutes after treatment, cultures were taken from the inferior conjunctival
      sac in both eyes. Following incubation at 35 degrees for 48 hours, the numbers of
      colonies were counted and compared. The difference in the numbers of colonies in
      each pair of treated and control eyes was assessed for each drug and compared.
      RESULTS: The reduction in colony-forming units was highly significant for each of
      the three drugs tested (Wilcoxon signed-ranks test; p < 0.0001). There was no
      significant difference between percent reduction by the three drugs (Kruskal
      Wallis test; p = 0.68). Sterile cultures following preparation by PI, Oflox and
      Chex were obtained in 52%, 68% and 52%, respectively. CONCLUSIONS: The regimens
      tested were similarly effective in reducing conjunctival commensals. They may all
      be considered as options for a quick prophylaxis against infection following
      suture removal in an outpatient setting.

PMID- 15948792
TI  - The presence of Propionibacterium spp. in the vitreous fluid of uveitis patients
      with sarcoidosis.
AB  - PURPOSE: An immunological reaction to a bacterial antigen, such as Mycobacterium
      tuberculosis or Propionibacterium spp., is suspected to be an initial mechanism
      in the disorder known as sarcoidosis. We investigated whether or not P. acnes, P.
      granulosum or M. tuberculosis are present in the vitreous fluid of eyes suffering
      from uveitis with sarcoidosis. METHODS: Using polymerase chain reaction, we
      analysed the presence of P. acnes, P. granulosum and/or M. tuberculosis DNA in
      vitreous samples taken from six eyes with sarcoidosis and six control eyes.
      RESULTS: Among the six uveitis eyes with sarcoidosis, we detected P. acnes DNA in
      two eyes, P. granulosum DNA in four eyes, and both P. acnes and P. granulosum DNA
      in one eye, but no Propionibacterium spp. in the control eyes. M. tuberculosis
      DNA was not present in any of the patient or control eyes. CONCLUSIONS: This is
      the first report indicating the presence of Propionibacterium spp. and/or its DNA
      in the vitreous fluid of sarcoidic eyes with uveitis. This, therefore, supports
      the idea that Propionibacterium spp. are involved in the aetiology of uveitis in
      sarcoidosis.

PMID- 15948793
TI  - Increased CD40 ligand in patients with acute anterior uveitis.
AB  - PURPOSE: The inflammatory response in acute anterior uveitis (AU) is believed to
      be primarily mediated by autoreactive T-cells. We wanted to evaluate whether the
      T-cell activation marker CD40 ligand is involved in the AU immunopathogenesis.
      METHODS: We evaluated the expression of the CD40 ligand on CD4+ T-cells, CD8+ T
      cells and CD19+ B-cells on peripheral blood mononuclear cells using flow
      cytometry in six patients with unilateral AU, six patients with monosymptomatic
      optic neuritis (ON) as inflammatory controls, and in six healthy controls. The ex
      vivo induction of the CD40 ligand on T-cells in patients and controls was also
      studied. RESULTS: A significantly higher expression of the CD40 ligand on both
      CD4+ (p < 0.05) and CD8+ (p < 0.05) T-cells in patients with AU compared to ON
      patients and healthy controls was found. There was a significantly higher
      induction of the CD40 ligand on CD8+ T-cells in AU patients compared to ON
      patients and healthy controls (p < 0.01). No differences in the B-cell population
      were observed between the three groups. CONCLUSION: Patients with AU had
      increased expression of the CD40 ligand on T-cells in the blood and expressed
      higher levels of the CD40 ligand when stimulated, compared to ophthalmological
      inflammatory controls and healthy controls. The data suggest that the CD40 ligand
      is involved in the development of AU.

PMID- 15948794
TI  - Expression of basic fibroblast growth factor in rabbit corneal alkali wounds in
      the presence and absence of granulocytes.
AB  - PURPOSE: To study the expression of basic fibroblast growth factor (bFGF) in the
      early phases of corneal wound healing in the presence or absence of granulocytes.
      METHODS: A central penetrating corneal alkali wound was inflicted to one eye in
      each of 14 rabbits under general anaesthesia. Subsequently, seven of the rabbits
      were given fucoidin i.v. for 36 hours in order to block the selectins on the
      vascular endothelium, thus preventing blood granulocytes from entering the
      tissues. Then, corneas were prepared, stained for bFGF and evaluated by light
      microscopy. RESULTS: Whereas normal corneal epithelium expressed bFGF weakly,
      conjunctival epithelium did so strongly, particularly the goblet cells. The
      corneal endothelium showed medium staining, while keratocytes and vascular
      endothelial cells did not consistently express bFGF. After 36 hours of wound
      healing, a marked up-regulation of bFGF expression was observed in the corneal
      epithelial and endothelial cells, as well as in the keratocytes, that were
      migrating into the wound. No other changes were noted. None of these features
      were modulated when granulocyte emigration was prevented by fucoidin
      administration. CONCLUSIONS: The difference in bFGF expression between the
      corneal and conjunctival epithelium suggests a role for this growth factor in the
      barrier function at the limbus. Moreover, the specific presence of bFGF in cells
      migrating into the wound indicates the participation of bFGF in corneal wound
      healing. Expression of bFGF was independent of granulocytes.

PMID- 15948795
TI  - Alpha-1--antitrypsin in aqueous humour from patients with corneal allograft
      rejection.
AB  - PURPOSE: To investigate the presence and concentration of alpha1-antitrypsin in
      aqueous humour at the time of corneal rejection and to compare results obtained
      from patients with reversible and irreversible rejection. METHODS: Samples of
      aqueous humour were obtained from 17 patients with acute corneal endothelial
      allograft rejection. The presence of alpha1-antitrypsin in aqueous humour was
      confirmed by immunoblotting and measured employing a sandwich ELISA. Total
      protein concentrations in aqueous humour were measured using Bradford's method.
      The outcome of corneal rejection episodes was determined 1 month after diagnosing
      corneal rejection and described as reversible or irreversible rejection. RESULTS:
      alpha1-antitrypsin was detected in aqueous humour. Patients with reversible
      rejection had significantly higher alpha1-antitrypsin concentration than patients
      with irreversible rejection (p = 0.044). There was no significant difference in
      total protein concentrations (p = 0.745), and no correlation was found between
      alpha1-antitrypsin and total protein concentrations (p = 0.368). CONCLUSIONS:
      alpha1-antitrypsin in aqueous humour seems to signal a favourable outcome of
      corneal rejection. The possible mechanism is discussed.

PMID- 15948796
TI  - Chromosomal imbalances in some benign orbital tumours.
AB  - PURPOSE: To examine benign orbital tumours for chromosomal imbalances. METHODS:
      Specimens obtained from orbital tumours were screened for chromosomal imbalances
      using high resolution comparative genomic hybridization (CGH). The imbalances
      detected by CGH were confirmed by using fluorescence in situ hybridization (FISH)
      and loss of heterozygosity (LOH) analysis. RESULTS: Chromosomal gains or losses
      were seen in 4/6 pleomorphic adenomas (gains at 8q; losses at 4p, 5p, 8p, 11p and
      14q), 2/4 schwannomas (losses at 16p and 22q), and 1/9 cavernous haemangiomas
      (losses at 13q). Compared to previous studies of pleomorphic adenomas using G
      band analysis, chromosomal imbalances were more frequently detected by using CGH.
      Gains of 8q11-q22 and losses of 4p15-pter, 11p12-p15, and 14q12-q23 in
      pleomorphic adenomas, losses of 16p12-p13 in schwannomas, and losses of 13q32
      qter in cavernous haemangiomas have not been reported previously. CONCLUSIONS: A
      range of chromosomal imbalances was detected even within tumours of the same
      histological subtype. We did not observe common chromosomal gains or losses that
      were characteristic for orbital presentation of the tumours. The clinical
      relevance of the abnormalities is uncertain, but they may indicate the position
      of genes that could play a role in tumour development.

PMID- 15948797
TI  - Ethmoidal osteoma with intraorbital extension: excision through a transcutaneous
      paranasal incision.
AB  - PURPOSE: To describe a case of conjunctival hyperaemia and proptosis of the right
      eye. METHODS: Three-dimensional computed tomography (CT) was performed to reveal
      the size and position of a lesion of osseous density extending into the right
      orbit. The lesion was then excised using a right paranasal transcutaneous
      approach. RESULTS: The pathology report suggested ethmoidal osteoma. The
      postoperative course was uncomplicated and the lesion did not recur during a 5
      year follow-up period. Repeated postoperative ophthalmic examinations revealed
      preservation of visual acuity and visual fields postoperatively. DISCUSSION:
      Diagnosis is based on imaging studies, especially CT and three-dimensional CT
      scans. A three-dimensional CT scan is critical in understanding the actual
      dimensions of the tumour and its relations with other structures. Surgical
      removal is indicated in cases with orbital matrix compression and displacement. A
      transcutaneous paranasal approach allows for increased exposure of affected
      structures.

PMID- 15948798
TI  - Premacular membrane peeling without removal of subretinal granuloma in an eye
      with ocular toxocariasis.

PMID- 15948800
TI  - Efficacy and safety of limbal anaesthesia for clear cornea phacoemulsification.

PMID- 15948802
TI  - Survival after primary enucleation of largest uveal melanomas.

PMID- 15948806
TI  - Personal view: food for thought--western lifestyle and susceptibility to Crohn's
      disease. The FODMAP hypothesis.
AB  - Susceptibility to the development of Crohn's disease involves a combination of
      genetic and environmental factors. The association of Crohn's disease with
      westernization has implicated lifestyle factors in pathogenesis. While diet is a
      likely candidate, evidence for specific changes in dietary habits and/or intake
      has been lacking. A new hypothesis is proposed, by which excessive delivery of
      highly fermentable but poorly absorbed short-chain carbohydrates and polyols
      (designated FODMAPs--Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to
      the distal small intestinal and colonic lumen is a dietary factor underlying
      susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs
      in the distal small and proximal large intestine induces conditions in the bowel
      that lead to increased intestinal permeability, a predisposing factor to the
      development of Crohn's disease. Evidence supporting this hypothesis includes the
      increasing intake of FODMAPs in western societies, the association of increased
      intake of sugars in the development of Crohn's disease, and the previously
      documented effects of the ingestion of excessive FODMAPs on the bowel. This
      hypothesis provides potential for the design of preventive strategies and raises
      concern about current enthusiasm for putative health-promoting effects of
      FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's
      disease is to identify predisposing environmental factors. Such an achievement
      might lead to the development of preventive strategies for, and the definition
      of, possible target for changing the natural history of this serious disease. The
      present paper describes a new hypothesis for one such environmental factor.

PMID- 15948807
TI  - Meta-analysis: role of Helicobacter pylori eradication in the prevention of
      peptic ulcer in NSAID users.
AB  - AIM: To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer
      in non-steroidal anti-inflammatory drug users by means of a meta-analysis.
      MATERIAL AND METHODS: A systematic search was performed in MEDLINE, EMBASE, the
      Cochrane Controlled Trials Register and the AGA congress. Randomized trials
      comparing H. pylori eradication vs. non-eradication or eradication vs. a proton
      pump inhibitor in patients receiving a non-steroidal anti-inflammatory drug were
      selected. RESULTS: Five studies and 939 patients were included in the analysis;
      34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64
      of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence
      interval: 0.20-0.93). Sub-analyses showed a significant reduction of risk for non
      steroidal anti-inflammatory drug-naive (odds ratio = 0.26; 95% confidence
      interval: 0.14-0.49) but not for previously treated patients (odds ratio = 0.95,
      95% confidence interval: 0.53-1.72). Two studies with a total of 385 patients
      compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a
      peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump
      inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27-43.6).
      CONCLUSION: Helicobacter pylori eradication reduces the incidence of peptic ulcer
      in the overall population receiving non-steroidal anti-inflammatory drugs. It
      appears to be especially effective when performed in non-steroidal anti
      inflammatory drug-naive patients. Nonetheless, eradication seems less effective
      than treatment with a maintenance proton pump inhibitor for preventing non
      steroidal anti-inflammatory drug-associated ulcers.

PMID- 15948808
TI  - High rate of Helicobacter pylori eradication with sequential therapy in elderly
      patients with peptic ulcer: a prospective controlled study.
AB  - BACKGROUND: Helicobacter pylori eradication rates with triple therapies are
      decreasing, and few data in elderly patients are available. A 10-day sequential
      regimen succeeded in curing such H. pylori infection in unselected patients. AIM:
      To compare this sequential regimen and the standard triple therapy for H. pylori
      eradication in geriatric patients with peptic ulcer. METHODS: Overall, 179 H.
      pylori-infected patients with peptic ulcer were enrolled (mean age: 69.5 years;
      range: 65-83). Patients were randomized to 10-day sequential therapy (rabeprazole
      20 mg b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by
      rabeprazole 20 mg, clarithromycin 500 mg and tinidazole 500 mg, all b.d., for the
      remaining 5 days) or standard 7-day triple regimen (rabeprazole 20 mg,
      clarithromycin 500 mg and amoxicillin 1 g, all b.d.). Helicobacter pylori status
      was assessed by histology and rapid urease test at baseline and 4-6 weeks after
      completion of treatment. RESULTS: The sequential regimen achieved eradication
      rates significantly higher in comparison with the standard regimen at both
      intention-to-treat (94% vs. 80%; P = 0.008) and per-protocol (97% vs. 83%; P =
      0.006) analyses. In both treatment groups, compliance to the therapy was high (>
      95%), and the rate of mild side-effects was similarly low (< 12%). At repeated
      upper endoscopy, peptic ulcer lesions were healed in 97% patients, without a
      statistically significant difference between the sequential regimen and the
      standard triple therapy. CONCLUSIONS: In elderly patients with peptic ulcer
      disease, the 10-day sequential treatment regimen achieved significantly higher
      eradication rates in comparison with standard triple therapy.

PMID- 15948809
TI  - Variation in the use of H. pylori tests in UK general practice--a qualitative
      study.
AB  - BACKGROUND: Although serology is the main Helicobacter pylori test used by
      general practitioners in the UK, there is no information available on variation
      in requesting rates. AIM: To explore the reasons for any variation in H. pylori
      serology testing by general practices in the UK using qualitative methods.
      METHODS: Serology requesting rates were determined using laboratory and
      population data. Staff from randomly selected practices in the lowest and highest
      quintiles of testing attended focus groups to discuss the management of H. pylori
      and dyspepsia. Transcribed data were analysed using an interpretative
      phenomenological approach. RESULTS: Serology submission varied 600-fold (0.1
      59/1000 population/year) and H. pylori positivity rate 17-100%. Low-testing
      practices were less aware of the benefits of H. pylori testing and had shorter
      endoscopy waiting times. They preferred endoscopy diagnosis over serology test.
      Three high-testing practices had a high non-white population with high H. pylori
      positivity. Most staff knew little about the predictive value of serology, the
      availability of urea breath test on prescription or the existence of a stool
      test. CONCLUSIONS: Seroprevalence of H. pylori is still high in dyspeptics,
      especially in non-white populations. Laboratories and primary care trusts should
      audit H. pylori requests and endoscopy referrals, target education at high
      endoscopy referrers and low H. pylori testers and inform clinicians of the more
      accurate H. pylori tests and NICE dyspepsia guidance.

PMID- 15948810
TI  - Primary prophylaxis of variceal bleeding in cirrhotics unable to take beta
      blockers: a randomized trial of ligation.
AB  - AIM: To compare endoscopic banding ligation vs. no treatment in cirrhotics with
      intolerance or contraindications to beta-blockers for prevention of first
      bleeding in portal hypertension. METHODS: A sample size of 214 was planned with
      all sizes of varices. However, the trial was stopped due to increased bleeding in
      52 patients in the ligation group. The baseline severity liver disease and
      endoscopic features were similar. Ligation group: 25 (M/F = 21/4, mean age: 60 +/
      9.37 years); 27 not-treated group: 27 (M/F = 17/10, mean age: 63 +/- 10.27).
      RESULTS: The mean follow-up period was 19.5 +/- 13.3 months: five bled in the
      ligation group (20%), three from varices (two after banding at 11 and 17 days;
      one during the procedure), and two from gastropathy; two bled in the not-treated
      group (7%- two both varices) (P = 0.24). There were seven deaths in the ligation
      group and 11 in the not-treated group (P = 0.39). CONCLUSION: Sixty per cent of
      the bleeding in the banding group was probably iatrogenic, requiring the study to
      be stopped. Endoscopic banding ligation was no better than no treatment. This
      study suggests that ligation may be harmful when used as primary prophylaxis,
      similar to prophylactic sclerotherapy in the past.

PMID- 15948811
TI  - Gender and liver fibrosis in chronic hepatitis: the role of iron status.
AB  - BACKGROUND: The role of gender in the progression of fibrosis in chronic
      hepatitis C is still under investigation. AIM: To investigate whether gender
      affects the progression of liver disease and/or hides other risk factors.
      METHODS: A prospective series of 121 consecutive patients with chronic hepatitis
      C underwent liver biopsy. Grading and staging for chronic hepatitis were each
      evaluated according to Ishak's classification. RESULTS: In univariate and
      multivariate analysis on the whole group of patients, male gender was not
      associated either with significant liver fibrosis (Ishak's score > 2) or with
      cirrhosis (Ishak's score > 4). On the contrary, in univariate analysis on
      patients aged < or = 50 years, male gender was nearly significantly (P = 0.06)
      predictive of liver fibrosis, whereas it was not in patients > 50 years. Hepatic
      iron grading, along with age, was an independent factor associated with fibrosis.
      Moreover, the values of all the variables which describe iron status were
      significantly higher in males aged < or = 50 years in comparison with females of
      the same age. CONCLUSIONS: In chronic hepatitis C, male gender may be predictive
      of liver fibrosis only in patients aged < or = 50 years. Among fibrogenetic
      factors hidden by gender, iron status could play a major role.

PMID- 15948812
TI  - Long-term healing of Crohn's anal fistulas with fibrin glue injection.
AB  - BACKGROUND: Injecting fibrin glue has proved to be an effective means of treating
      anal fistulas (AF). There has been some debate, however, as to whether this
      technique should be used on the AF often involved in Crohn's disease (CD). AIM:
      To assess the effectiveness of injecting heterologous fibrin glue as a means of
      treating AF refractory to immunosuppressive treatment in patients with CD.
      METHODS: Fourteen CD patients (five men and nine women, average age 42 years)
      presenting with refractory AFs were included in this study. Heterologous fibrin
      glue was injected into the fistula tract under general anaesthesia under
      continuous endosonographic monitoring using a 7.5-MHz blind linear probe. The
      patients were followed up clinically and ultrasonographically for 3 months after
      the procedure, and then at regular intervals. RESULTS: Three months after the
      fibrin glue injection, the fistulas had completely dried up in 10 patients (71%),
      the leakage had decreased in one patient (7%), and no improvement was observed in
      the other three patients (21%). Endosonographic findings showed that the fistula
      tract had completely disappeared in two cases (14%). The fistula tract was found
      to be non-permeable in eight cases (57%), and no change in the fistula was
      observed in four patients (29%). At the end of the follow-up period [average 23.4
      months (12-26 months)], the leakage had completely dried up in eight of the 14
      patients (57%). No side effects were observed. CONCLUSION: Nearly 2 years after
      the use of a heterologous fibrin glue to treat an AF, over half of the patients
      with CD showed clinical signs of remission. Because it is easy to use and
      harmless as well as being effective, this method provides a good alternative to
      classical methods of surgical treatment.

PMID- 15948813
TI  - Factors predisposing to peptic ulcer disease in asymptomatic cirrhotic patients.
AB  - BACKGROUND: There is a high prevalence of peptic ulcer in cirrhotic patients, but
      the pathogenesis of peptic ulcer in cirrhosis remains inconclusive. AIM: To
      investigate factors associated with peptic ulcer and to evaluate peptic ulcer
      prevalence in asymptomatic cirrhotic patients. METHODS: A total of 130 cirrhotics
      were recruited into the study for endoscopic screening. Data were collected and
      biochemical tests were done. Doppler ultrasound was used to assess the portal
      vein velocity and size. Patients underwent endoscopy for the presence of varices
      and peptic ulcer. Helicobacter pylori infection was confirmed by urease test,
      histology and 14C-urea breath test. Statistical analysis was performed. RESULTS:
      Peptic ulcer was detected in 50 (39%) cases. Between peptic ulcer and non-peptic
      ulcer groups, there were no significant differences in age, sex, alcoholic
      drinking, smoking, non-steroidal anti-inflammatory drug use, portal vein velocity
      and size, except for H. pylori infection (P = 0.006), serum albumin (P = 0.02)
      and Child-Pugh score (P = 0.03). By multivariate analysis, H. pylori infection
      (OR: 3.26; 95% CI: 1.49-7.13; P = 0.003), Child-Pugh classes B (OR: 2.48; 95% CI:
      1.04-5.91; P = 0.04) and C (OR: 3.26; 95% CI: 1.2-8.81; P = 0.02) were
      independently associated with peptic ulcer. CONCLUSION: H. pylori infection and
      advanced cirrhosis are important factors associated with active peptic ulcer.

PMID- 15948814
TI  - Comparison of the effects of immediate-release omeprazole powder for oral
      suspension and pantoprazole delayed-release tablets on nocturnal acid
      breakthrough in patients with symptomatic gastro-oesophageal reflux disease.
AB  - BACKGROUND: Many patients treated with a proton-pump inhibitor for gastro
      oesophageal reflux disease or erosive oesophagitis still have substantial night
      time gastric acidity. A previous trial of a new immediate-release omeprazole oral
      suspension suggested that nocturnal gastric acidity could be more effectively
      controlled with a bedtime dose of immediate-release omeprazole than with a
      delayed-release proton-pump inhibitor administered before dinner or at bedtime.
      AIM: To compare the ability of immediate-release omeprazole with pantoprazole to
      control nocturnal gastric acidity, when they were dosed once daily and twice
      daily. METHODS: Thirty-six patients with nocturnal gastro-oesophageal reflux
      disease symptoms received immediate-release omeprazole and pantoprazole in this
      open-label, randomized-crossover trial. Median gastric pH, the percentage of time
      with gastric pH > 4 and the percentage of patients with nocturnal acid
      breakthrough, were evaluated with 24-h pH monitoring. RESULTS: Repeated once
      daily (bedtime) dosing with immediate-release omeprazole suspension produced
      significantly better nocturnal gastric acid control than repeated once daily
      (predinner) or twice daily (prebreakfast and bedtime) dosing with pantoprazole
      delayed-release tablets (median pH: 4.7 vs. 2.0 and 1.7; percentage of time pH >
      4: 55 vs. 27 and 34; nocturnal acid breakthrough: 53 vs. 78 and 75). Twice daily
      dosing (prebreakfast and bedtime) with immediate-release omeprazole 20 and 40 mg
      achieved the best night-time control of gastric acidity. Repeated once daily
      bedtime dosing with immediate-release omeprazole 40 mg and twice daily dosing
      with pantoprazole 40 mg gave similar 24-h pH control. No safety issues were
      associated with either drug in this trial. CONCLUSIONS: Dosed once daily at
      bedtime, immediate-release omeprazole reduced nocturnal gastric acidity to a
      degree not observed with once daily dosing of delayed-release proton-pump
      inhibitors.

PMID- 15948815
TI  - Postprandial oesophageal integrated acidity is a reliable predictor of gastro
      oesophageal reflux disease.
AB  - BACKGROUND: Measurement of oesophageal acid exposure parameters postprandially
      has been shown to distinguish gastro-oesophageal reflux disease patients from
      normal individuals. AIMS: To calculate the accuracy of postprandial oesophageal
      integrated acidity in diagnosing gastro-oesophageal reflux disease. METHODS:
      Ambulatory 24-h pH studies of 626 patients were analysed retrospectively. Gastro
      oesophageal reflux disease, defined as pH < 4 for > 4.2% of time, was identified
      in 305 subjects. Postprandial oesophageal integrated acidity was measured for 2
      and 3 h after the largest meal peak as determined from gastric pH. Postprandial
      symptom-associated probability was calculated. RESULTS: Gastro-oesophageal reflux
      disease subjects had a greater postprandial oesophageal integrated acidity than
      non-gastro-oesophageal reflux disease subjects [median (IQR): 0.57 (0.08-2.66)
      vs. 0.03 (0.01-0.15) mmol*h/L]. Median postprandial oesophageal integrated
      acidity did not differ with gender or age in gastro-oesophageal reflux disease
      and non-gastro-oesophageal reflux disease subjects (P > 0.05 for all). A 3-h
      postprandial oesophageal integrated acidity value of 0.121 mmol*h/L had a 71.1%
      sensitivity and 71.7% specificity in diagnosing gastro-oesophageal reflux
      disease. Gastro-oesophageal reflux disease subjects with symptoms had a higher
      postprandial oesophageal integrated acidity than those without (P = 0.043),
      whereas non-gastro-oesophageal reflux disease subjects with and without symptoms
      did not differ (P = 0.74). The correlation between symptom-associated probability
      and postprandial oesophageal integrated acidity was poor (gastro-oesophageal
      reflux disease: r = 0.15; non-gastro-oesophageal reflux disease: r = 0.25).
      CONCLUSION: Postprandial oesophageal integrated acidity provides a robust
      estimation of oesophageal acid exposure and may predict symptoms in gastro
      oesophageal reflux disease patients.

PMID- 15948816
TI  - Gastro-oesophageal reflux is more prevalent in Western dyspeptics: a prospective
      comparison of British and South-East Asian patients with dyspepsia.
AB  - BACKGROUND: There is a paucity of data directly comparing dyspepsia in Western
      and Eastern populations. AIM: To compare clinical symptoms, epidemiological
      factors and endoscopic diagnoses in two sample populations with dyspepsia from
      the United Kingdom and South-East Asia in a cross-sectional study. METHODS:
      Patients with uncomplicated dyspepsia attending endoscopy units in Leeds, UK, and
      Kuala Lumpur, Malaysia, were prospectively interviewed and underwent subsequent
      endoscopy. RESULTS: A total of 1003 Malaysian patients (January 2002 to August
      2003) and 597 Caucasian British patients (January 2000 to October 2002) were
      studied. The mean age was 48.7 +/- 15.8 and 47.5 +/- 13.8 years for the Malaysian
      and British patients respectively (P = NS). There was a higher proportion of
      cigarette smoking (35.7% vs. 12.4%, P < 0.0001) and alcohol consumption (34.4%
      vs. 2.0%, P < 0.0001) amongst British patients, but no difference in non
      steroidal anti-inflammatory drug use nor having Helicobacter pylori infection.
      Gastro-oesophageal reflux disease (GERD) symptoms were more common in British
      compared with South-East Asian patients [heartburn (72% vs. 41%), regurgitation
      (66% vs. 29.8%) and dysphagia (21.1% vs. 7.3%), P < 0.0001]. This correlated with
      an increased endoscopic finding of oesophagitis (26.8% vs. 5.8%) and columnar
      lined oesophagus (4.4% vs. 0.9%) amongst British patients (P < 0.001). A logistic
      regression model revealed that British Caucasian race (OR 9.7; 95% CI = 5.0
      18.8), male gender (OR 2.0; 95% CI = 1.4-2.9) and not having H. pylori infection
      (OR 0.5; 95% CI = 0.3-0.7) were independent predictors for oesophagitis.
      CONCLUSION: GERD is more common in British compared with South-East Asian
      dyspeptic patients suggesting that race and/or western lifestyle are important
      risk factors.

PMID- 15948817
TI  - Efficacy of bowel preparation with the use of a prepackaged, low fibre diet with
      a low sodium, magnesium citrate cathartic vs. a clear liquid diet with a standard
      sodium phosphate cathartic.
AB  - BACKGROUND: A colon free of faecal residue is required for accurate diagnostic
      colonoscopy. Patient tolerance of his/her colonoscopy cathartic regimen affects
      patient compliance and willingness to undergo repeated examinations. AIM: To
      determine whether a meal could be consumed during standard bowel preparation.
      METHODS: This was a randomized, endoscopists' blinded comparison of the
      tolerability and efficacy of a prepackaged, low-residue diet (NutraPrep) combined
      with the LoSo Prep bowel cleansing system, which contains magnesium citrate,
      bisocodyl tablets and a bisocodyl suppository (NP-LS regimen), compared with a
      clear liquid diet and a double-dose sodium phosphate (Fleet Phospho-soda) regimen
      (2F regimen). Outcome measures included efficacy of bowel preparation, patient
      preparation tolerability, side-effects and patient safety. RESULTS: A total of
      506 patients completed the study, 222 randomized to 2F and 284 to NP-LS. The NP
      LS regimen resulted in significantly better colon cleansing in terms of the
      proportion with good or excellent results (P = 0.025) and in significantly better
      patient tolerance and willingness to repeat the cathartic preparation (P < 0.01).
      CONCLUSION: The NP-LS regimen proved superior to the 2F regimen.

PMID- 15948818
TI  - Gender difference on the symptoms, health-seeking behaviour, social impact and
      sleep quality in irritable bowel syndrome: a Rome II-based survey in an apparent
      healthy adult Chinese population in Taiwan.
AB  - BACKGROUND: Little is known about the gender effect on irritable bowel syndrome
      in Asia. AIM: To assess the gender difference in Chinese subjects with irritable
      bowel syndrome meeting Rome II criteria. METHODS: Irritable bowel syndrome was
      identified from an apparently healthy adult population receiving a routine health
      maintenance program (n = 2018). RESULTS: Female gender is not a factor associated
      with irritable bowel syndrome or irritable bowel syndrome-related health care
      seeking behaviour. Female irritable bowel syndrome subjects, irrespective of
      consulting behaviour for irritable bowel syndrome, are likely to have < 3 bowel
      movements/week, hard/lumpy stools and abdominal fullness/bloating (P < 0.05).
      Female irritable bowel syndrome subjects are prone to be absent from school/work
      with more days of absenteeism, irrespective of consultation status (P < 0.05).
      Only female irritable bowel syndrome consulters have more absenteeism for their
      irritable bowel syndrome-related symptoms, reporting more sleep disturbances than
      their male counterparts (P < 0.001). CONCLUSIONS: In an apparent healthy adult
      population in Taiwan, gender difference is present in Rome II defined Chinese
      subjects with irritable bowel syndrome as regards bowel symptoms, social impact
      and sleep quality. Female predominance was not found in irritable bowel syndrome
      subjects and irritable bowel syndrome-related health care-seeking behaviour in
      the current population. Both irritable bowel syndrome non-consulters and
      consulters have similar gender difference profiles in presenting symptoms,
      suggesting that bowel symptoms per se may not be the only factor leading to
      health care-seeking behaviour. The gender differences in sleep problems were
      observed solely in irritable bowel syndrome consulter.

PMID- 15948819
TI  - Time to remission with budesonide in collagenous colitis.

PMID- 15948821
TI  - Saccharomyces boulardii and antibiotic-associated diarrhoea in children.

PMID- 15948823
TI  - An evolving approach to understanding plant adaptation.

PMID- 15948824
TI  - Challenges to plant megadiversity: how environmental physiology can help.
      Environmental Physiology and Plant Diversity in Mexico: From Molecules to
      Ecosystems. A symposium within the XVI National Botanical Congress, Sociedad
      Botanica de Mexico, Oaxaca, Mexico, October 2004.

PMID- 15948825
TI  - Genetic transformation: a powerful tool for dissection of adaptive traits in
      trees.
AB  - Plant transformation and regeneration systems have become indispensable parts of
      gene discovery and functional characterization over the last two decades.
      Adoption of transformation methods in studies of plant adaptation to natural
      environments has been slow. This is a result of poor genomic knowledge and
      inefficient transformation systems for species dominating terrestrial ecosystems,
      and logistical difficulties in conducting field tests of genetically engineered
      organisms. In trees, where long generation cycles, high background polymorphism,
      large sizes and outcrossing systems of mating make production of near-isogenic
      lines and large experiments difficult, transformation is an attractive
      alternative for establishing direct linkages between genes and adaptively
      significant phenotypes. Here, we outline the capabilities, challenges, and
      prospects for transformation to become a significant tool for studying the
      ecophysiological adaptation of trees to the environment. Focusing on poplars
      (genus Populus) as model system, we describe how transformation-based approaches
      can provide insights into the genes that control adaptive traits. The
      availability of the poplar genome sequence, along with its large expressed
      sequences tag (EST) databanks, facile transformation and rapid growth, enable
      reverse genetic approaches to be used to test virtually any hypothesis of gene
      function.

PMID- 15948826
TI  - Nitrogen storage and seasonal nitrogen cycling in Populus: bridging molecular
      physiology and ecophysiology.
AB  - While both annual and perennial plants store nitrogen resources during the
      growing season, seasonal N cycling is a hallmark of the perennial habit. In
      Populus the vegetative storage proteins BSP, WIN4 and PNI288 all play a role in N
      storage during active growth, whereas BSP is the major form of reduced N storage
      during winter dormancy. In this review we explore cellular and molecular events
      implicated in seasonal N cycling in Populus, as well as environmental cues that
      modulate both the phenology of seasonal N cycling, and the efficiency and
      proficiency of autumn N resorption. We highlight recent advances that have been
      made using Populus genomics resources to address processes germane to seasonal N
      cycling. Genetic and genetological studies are enabling us to connect our
      understanding of seasonal N cycling at molecular and cellular levels with that at
      ecophysiological levels. With the genomics resources and foundational knowledge
      that are now in place, Populus researchers are poised to build an integrative
      understanding of seasonal N cycling that spans from genomes to ecosystems.

PMID- 15948827
TI  - Characterization of transgenic poplar with ectopic expression of pine cytosolic
      glutamine synthetase under conditions of varying nitrogen availability.
AB  - The present study addresses the hypothesis that enhanced expression of glutamine
      synthetase (GS) in transgenic poplar, characterized by the ectopic expression of
      pine cytosolic GS, results in an enhanced efficiency of nitrogen (N) assimilation
      and enhanced growth. Transgenic and control poplar were supplied with low and
      high N levels and the role of ectopic expression of the pine GS in growth and N
      assimilation was assessed by using amino acid analysis, (15)N enrichment,
      biochemical analyses, and growth measurements. While leaves of transgenic poplar
      contained 85% less (P < 0.01) free ammonium than leaves of nontransgenic control
      plants, leaves of transgenics showed increases in the levels of free glutamine
      and total free amino acids. Transgenic poplar lines also displayed significant
      increases in growth parameters when compared with controls grown under both low
      (0.3 mm) and high (10 mm) nitrate conditions. Furthermore, (15)N-enrichment
      experiments showed that 27% more (P < 0.05) (15)N was incorporated into
      structural compounds in transgenic lines than in nontransgenic controls. Using
      the methods described here, we present direct evidence for increased N
      assimilation efficiency and growth in GS transgenic lines.

PMID- 15948828
TI  - Short-term physiological and developmental responses to nitrogen availability in
      hybrid poplar.
AB  - Nitrogen fertilization induces dramatic changes in the growth and development of
      plants, including forest trees. In this study we examined short-term responses of
      hybrid poplar, Populus balsamifera ssp. trichocarpa x deltoides, to N
      fertilization. Glasshouse-grown saplings subjected to limiting, intermediate, and
      luxuriant levels of ammonium nitrate over a 28 d time course demonstrated rapid
      changes to whole-plant architecture and biomass accumulation. Nitrogen-associated
      shifts in allocation occurred in temporally distinct stages. Nitrogen
      availability modulated parameters that affect carbon gain, including light
      saturated net photosynthesis and leaf area. These parameters were affected by N
      induced changes to leaf maturation and senescence. Leaf area was also affected by
      N-induced sylleptic branch development. Genes encoding vegetative storage
      proteins and starch biosynthetic enzymes exhibited contrasting patterns of
      expression under differential N availability. A gene encoding a previously
      uncharacterized putative pectin methylesterase inhibitor displayed expression
      patterns comparable to the starch biosynthetic genes. The results of this study
      illustrate the phenotypic plasticity that P. balsamifera ssp. trichocarpa x
      deltoides exhibits in response to differential N availability.

PMID- 15948829
TI  - Productivity, leaf traits and carbon isotope discrimination in 29 Populus
      deltoides x P. nigra clones.
AB  - Here we tested whether some leaf traits could be used as predictors for
      productivity in a range of Populus deltoides x P. nigra clones. These traits were
      assessed in 3-yr-old rooted cuttings from 29 clones growing in an open field
      trial, in a five randomized complete block design, under optimal irrigation.
      Variables were assigned to four groups describing productivity (above-ground
      biomass, total leaf area), leaf growth (total number of leaves increment rate),
      leaf structure (area of the largest leaf, specific leaf area, carbon and nitrogen
      contents), and carbon isotope discrimination in the leaves (Delta). High-yielding
      clones displayed larger total leaf area and individual leaf area, while no
      correlation could be detected between productivity and either leaf structure or
      Delta. By contrast, Delta was negatively correlated with number of leaves
      increment rate and leaf N content. Our study shows that there is a potential to
      improve water-use efficiency in poplar without necessarily reducing the overall
      productivity.

PMID- 15948830
TI  - Jasmonic acid induces rapid changes in carbon transport and partitioning in
      Populus.
AB  - Here, we tested whether rapid changes in carbohydrate transport and partitioning
      to storage organs would be induced by jasmonic acid (JA), a plant-produced signal
      of herbivore attack known to induce resistance. Carbon-11, introduced as
      (11)CO(2), was used to track real-time carbohydrate transport and partitioning
      nondestructively in Populus species before and 12 h after application of JA to a
      single leaf. Jasmonic acid resulted in more rapid [(11)C]-photosynthate export
      from both local and systemic leaves, as well as greater partitioning of [(11)C]
      photosynthate to the stem and roots. In Populus tremuloides, following JA
      treatment, leaf starch decreased, but there was no change in photosynthetic rates
      or leaf soluble sugar concentration, indicating that recent photosynthate was
      diverted from starch accumulation in the leaf to other plant organs. Increasing
      the supply of photosynthate to roots and stems may shield resources from
      folivorous predators, and may also facilitate both storage and nutrient uptake,
      and ultimately lead to greater tolerance, either by enhancing regrowth capacity
      or by replacing nutrients consumed by herbivores.

PMID- 15948831
TI  - Does glutathione metabolism have a role in the defence of poplar against zinc
      excess?
AB  - Transition metals such as zinc (Zn) are essential micronutrients for many
      physiological processes, but they become toxic at elevated levels. Zinc is one of
      the most abundant trace heavy metals present in agro-ecosystems. Populus spp.
      have been suggested as good candidates for using to study the removal and/or
      immobilization of environmental organic and inorganic pollutants. In order to
      understand the physiological and biochemical bases of this assumption for Zn,
      plants of Populus deltoides x P. nigra (P. x euramericana) were grown in
      hydroponics with different concentrations of Zn [1 microm (control), and 1, 5 and
      10 mm] in the nutrient solution.Shoot biomass decreased at 5 and 10 mm Zn, while
      the Zn content of young leaves increased progressively with increasing Zn
      concentration (1-10 mm). Total glutathione (GSH+GSSG) content was reduced with
      increasing Zn concentration, while the contribution of oxidized to total
      glutathione increased. Despite these observations, semiquantitative reverse
      transcription-polymerase chain reaction (RT-PCR) revealed that the gene
      expression of GSH reductase (GR, chloroplastic and cytosolic isoform) and gamma
      glutamylcysteine synthetase (gamma-ECS) increased in young leaves of poplars
      treated with excess Zn. We conclude that GSH synthesis, consumption and redox
      status play a central role in the response of poplars to high concentrations of
      Zn.

PMID- 15948832
TI  - Mutations in CAX1 produce phenotypes characteristic of plants tolerant to
      serpentine soils.
AB  - Plant tolerance of serpentine soils is potentially an excellent model for
      studying the genetics of adaptive variation in natural populations. A large-scale
      viability screen of Arabidopsis thaliana mutants on a defined nutrient solution
      with a low Ca(2+) : Mg(2+) ratio (1 : 24 mol : mol), typical of serpentine soils,
      yielded survivors with null alleles of the tonoplast calcium-proton antiporter
      CAX1. cax1 mutants have most of the phenotypes associated with tolerance to
      serpentine soils, including survival in solutions with a low Ca(2+) : Mg(2+)
      ratio; requirement for a high concentration of Mg(2+) for maximum growth; reduced
      leaf tissue concentration of Mg(2+); and poor growth performance on 'normal'
      levels of Ca(2+) and Mg(2+). A physiological model is proposed to explain how
      loss-of-function cax1 mutations could produce all these phenotypes characteristic
      of plants adapted to serpentine soils, why 'normal' plants are unable to survive
      on serpentine soil, and why serpentine-adapted plants are unable to compete on
      'normal' soils.

PMID- 15948833
TI  - Transcript profiling of Eucalyptus xylem genes during tension wood formation.
AB  - Tension wood formed in response to gravitational force is a striking example of
      the plasticity of angiosperm wood. In this study our goal was to characterize the
      early changes in gene expression during tension wood formation in Eucalyptus.
      Using cDNA array technology, transcript profiling of 231 genes preferentially
      expressed in differentiating Eucalyptus xylem was followed from 6 h to 1 wk of a
      tension time course of artificially bent Eucalyptus trees. 196 genes were
      differentially regulated between control and bent trees, some exhibiting
      distinctive expression patterns related to changes in secondary cell wall
      structure and composition. For instance, expression of a cellulose synthase gene
      was well correlated with the appearance of the G-layers. Cluster correlation
      analysis revealed differential regulation of lignin biosynthetic genes and may
      also be used to help infer the function of unknown gene products. Eucalyptus wood
      transcriptome analysis during tension wood formation not only provided new clues
      into the transcriptional regulatory network of genes preferentially expressed in
      xylem, but also highlighted candidate genes responsible for the genetic and
      environmentally induced variation of wood quality traits.

PMID- 15948834
TI  - Nucleotide variation in genes involved in wood formation in two pine species.
AB  - Nucleotide diversity in eight genes related to wood formation was investigated in
      two pine species, Pinus pinaster and P. radiata. The nucleotide diversity
      patterns observed and their properties were compared between the two species
      according to the specific characteristics of the samples analysed. A lower
      diversity was observed in P. radiata compared with P. pinaster. In particular,
      for two genes (Pp1, a glycin-rich protein homolog and CesA3, a cellulose
      synthase) the magnitude of the reduction of diversity potentially indicates the
      action of nonneutral factors. For both, particular patterns of nucleotide
      diversity were observed in P. pinaster (high genetic differentiation for Pp1 and
      close to zero differentiation associated with positive Tajima's D-value for
      CesA3). In addition, KORRIGAN, a gene involved in cellulose-hemicellulose
      assembly, demonstrated a negative Tajima's D-value in P. radiata accompanied by a
      high genetic differentiation in P. pinaster. The consistency of the results
      obtained at the nucleotide level, together with the physiological roles of the
      genes analysed, indicate their potential susceptibility to artificial and/or
      natural selection.

PMID- 15948835
TI  - Genetic architecture of qualitative and quantitative Melampsora larici-populina
      leaf rust resistance in hybrid poplar: genetic mapping and QTL detection.
AB  - In order to elucidate the genetic control of resistance to Melampsora larici
      populina leaf rust in hybrid poplars, a Populus deltoides x P. trichocarpa F(1)
      progeny was analysed for qualitative and quantitative rust resistances. This
      progeny was evaluated for three components of quantitative resistance (latent
      period, uredinia number and uredinia size) to seven M. larici-populina strains in
      controlled conditions, and for one component of field susceptibility (rust
      colonization on the most infected leaf). One qualitative resistance locus
      inherited from P. deltoides, R(1), was localized on the genetic map. It
      segregates 1 : 1 in the F(1) progeny and is effective against four of the studied
      strains. QTL analysis was performed separately on R(1) and r(1) genotype subsets.
      An additional detection was conducted on the entire F(1) progeny for the three
      strains able to overcome R(1) and for MAX2. A total of nine QTLs were detected.
      Two had large, broad-spectrum effects. One (R(US)) is inherited from the P.
      trichocarpa parent; the other is inherited from P. deltoides and colocalized with
      R(1). Seven QTLs had only limited and specific effects. Significant interaction
      effects were detected mainly between the two major QTLs. Implications of these
      results for durable resistance breeding strategies, and possible benefits from
      the Populus genome sequence, are discussed.

PMID- 15948836
TI  - Gene expression patterns of trembling aspen trees following long-term exposure to
      interacting elevated CO2 and tropospheric O3.
AB  - Expression of 4600 poplar expressed sequence tags (ESTs) was studied over the
      2001-2002 growing seasons using trees of the moderately ozone (O(3))-tolerant
      trembling aspen (Populus tremuloides) clone 216 exposed to elevated CO(2) and/or
      O(3) for their entire 5-yr life history. Based on replication of the experiment
      in years 2001 and 2002, 238 genes showed qualitatively similar expression in at
      least one treatment and were retained for analysis. Of these 238 genes, 185 were
      significantly regulated (1.5-fold) from one year to the other in at least one
      treatment studied. Less than 1% of the genes were regulated 2-fold or more. In
      the elevated CO(2) treatment, relatively small numbers of genes were up
      regulated, whereas in the O(3) treatment, higher expression of many signaling and
      defense-related genes and lower expression of several photosynthesis and energy
      related genes were observed. Senescence-associated genes (SAGs) and genes
      involved in the flavonoid pathway were also up-regulated under O(3), with or
      without CO(2) treatment. Interestingly, the combined treatment of CO(2) plus O(3)
      resulted in the differential expression of genes that were not up-regulated with
      individual gas treatments. This study represents the first investigation into
      gene expression following long-term exposure of trees to the interacting effects
      of elevated CO(2) and O(3) under field conditions. Patterns of gene-specific
      regulation described in this study correlated with previously published
      physiological responses of aspen clone 216.

PMID- 15948837
TI  - The transcriptome of Populus in elevated CO2.
AB  - The consequences of increasing atmospheric carbon dioxide for long-term
      adaptation of forest ecosystems remain uncertain, with virtually no studies
      undertaken at the genetic level. A global analysis using cDNA microarrays was
      conducted following 6 yr exposure of Populus x euramericana (clone I-214) to
      elevated [CO(2)] in a FACE (free-air CO(2) enrichment) experiment. Gene
      expression was sensitive to elevated [CO(2)] but the response depended on the
      developmental age of the leaves, and < 50 transcripts differed significantly
      between different CO(2) environments. For young leaves most differentially
      expressed genes were upregulated in elevated [CO(2)], while in semimature leaves
      most were downregulated in elevated [CO(2)]. For transcripts related only to the
      small subunit of Rubisco, upregulation in LPI 3 and downregulation in LPI 6
      leaves in elevated CO(2) was confirmed by anova. Similar patterns of gene
      expression for young leaves were also confirmed independently across year 3 and
      year 6 microarray data, and using real-time RT-PCR. This study provides the first
      clues to the long-term genetic expression changes that may occur during long-term
      plant response to elevated CO(2).

PMID- 15948838
TI  - Allelic and population variation of microsatellite loci in aspen (Populus
      tremuloides).
AB  - To develop a robust basis for inferences about population genetics and evolution,
      this work assayed 192 aspens (Populus tremuloides) from 11 sites in Wisconsin,
      USA, for allelic and population variation at 16 microsatellite loci distributed
      across the Populus genome. Frequency distributions of fluorochrome-labeled
      alleles resolved by capillary electrophoresis were analyzed for relationships to
      repeat size and number. Population-level statistics were compared with those of
      other studies, especially in Populus. All loci were polymorphic, varying widely
      in the number of alleles per locus (mean = 8.25, range 2-20). Expected and
      observed heterozygosities were high (0.45 and 0.41, respectively), with little
      differentiation among populations (F(ST) = 0.006-0.045) and a moderate level of
      inbreeding (F(IS) = 0.09), intermediate among levels reported in studies based on
      isozymes. Contrary to several other reports, allele frequencies clustered tightly
      around the modal frequency, and the genetic diversity (measured as alleles per
      locus or as expected heterozygosity) was not related to either the repeat unit
      size or to the number of repeats.

PMID- 15948839
TI  - EST data suggest that poplar is an ancient polyploid.
AB  - We analysed the publicly available expressed sequence tag (EST) collections for
      the genus Populus to examine whether evidence can be found for large-scale gene
      duplication events in the evolutionary past of this genus. The ESTs were
      clustered into unigenes for each poplar species examined. Gene families were
      constructed for all proteins deduced from these unigenes, and K(S) dating was
      performed on all paralogs within a gene family. The fraction of paralogs was then
      plotted against the K(S) values, which resulted in a distribution reflecting the
      age of duplicated genes in poplar. Sufficient EST data were available for seven
      different poplar species spanning four of the six sections of the genus Populus.
      For all these species, there was evidence that a large-scale gene-duplication
      event had occurred. From our analysis it is clear that all poplar species have
      shared the same large-scale gene-duplication event, suggesting that this event
      must have occurred in the ancestor of poplar, or at least very early in the
      evolution of the Populus genus.

PMID- 15948840
TI  - A site-specific insertion sequence in flax genotrophs induced by environment.
AB  - A single-copy 5.7 kilobase (kb) DNA fragment, termed Linum Insertion Sequence 1
      (LIS-1), has been identified and characterized. This is one of the DNA changes
      associated with the environmentally induced heritable changes resulting in stable
      lines termed genotrophs in flax (Linum usitatissimum). The insertion sequence and
      its insertion site have been cloned from genomic libraries and sequenced. PCR
      products across the insertion and surrounding regions have also been cloned and
      sequenced. The 5.7 kb DNA fragment is inserted into a 3.7 kb EcoRI fragment in
      the plastic line (Pl) with the generation of a 3 base pair duplication at the
      insertion site, as well as additional sequence changes. The identical insertion
      was also found in other genotrophs and flax varieties. The intact element was not
      present in Pl but appeared to be generated by a reproducible series of complex
      rearrangements or insertion events. LIS-1 is the result of a targeted, highly
      specific, complex insertion event that occurs during the formation of some of the
      genotrophs, and occurs naturally in many flax and linseed varieties.

PMID- 15948841
TI  - Above-ground space sequestration determines competitive success in juvenile beech
      and spruce trees.
AB  - A 2-yr phytotron study was conducted to investigate the intra- and inter-specific
      competitive behaviour of juvenile beech (Fagus sylvatica) and spruce (Picea
      abies). Competitiveness was analysed by quantifying the resource budgets that
      occur along structures and within occupied space of relevance for competitive
      interaction. Ambient and elevated CO(2) and ozone (O(3)) regimes were applied
      throughout two growing seasons as stressors for provoking changes in resource
      budgets, growth and allocation to facilitate the competition analysis. The
      hypothesis tested was that the ability to sequester space at low structural cost
      will determine the competitive success. Spruce was a stronger competitor than
      beech, as displayed by its higher above-ground biomass increments in mixed
      culture compared with monoculture. A crucial factor in the competitive success of
      spruce was its ability to enlarge crown volume at low structural costs,
      supporting the hypothesis. Interspecific competition with spruce resulted in a
      size-independent readjustment of above-ground allocation in beech (reduced leaf :
      shoot biomass ratio). The efficient use of resources for above-ground space
      sequestration proved to be a parameter that quantitatively reflects
      competitiveness.

PMID- 15948842
TI  - A functional comparison of acclimation to shade and submergence in two
      terrestrial plant species.
AB  - Terrestrial plants experience multiple stresses when they are submerged, caused
      both by oxygen deficiency due to reduced gas diffusion in water, and by shade due
      to high turbidity of the floodwater. It has been suggested that responses to
      submergence are de facto responses to low light intensity. We investigated the
      extent to which submergence and shade induce similar acclimation responses by
      comparing two terrestrial Rumex species that differ in their responses to
      flooding. Our study confirms that there are strong similarities between
      acclimation responses to shade and submergence. Petiole length, specific leaf
      area (SLA), chlorophyll parameters and underwater light-compensation points
      changed at least qualitatively in the same direction. Maximum underwater
      photosynthesis rate, however, did discriminate between the functionality of the
      responses, as the acclimation to submergence appeared to be more effective than
      acclimation to shade at saturating light. We conclude that acclimation to
      submergence involves more than an increase in SLA to achieve the significant
      reduction of diffusion resistance for gas exchange between leaves and the water
      column.

PMID- 15948843
TI  - Elevated CO2 reduces leaf damage by insect herbivores in a forest community.
AB  - By altering foliage quality, exposure to elevated levels of atmospheric CO(2)
      potentially affects the amount of herbivore damage experienced by plants. Here,
      we quantified foliar carbon (C) and nitrogen (N) content, C : N ratio, phenolic
      levels, specific leaf area (SLA) and the amount of leaf tissue damaged by chewing
      insects for 12 hardwood tree species grown in plots exposed to elevated CO(2)
      (ambient plus 200 microl l(-1)) using free-air CO(2) enrichment (FACE) over 3 yr.
      The effects of elevated CO(2) varied considerably by year and across species.
      Elevated CO(2) decreased herbivore damage across 12 species in 1 yr but had no
      detectable effect in others. Decreased damage may have been related to lower
      average foliar N concentration and SLA and increased C : N ratio and phenolic
      content for some species under elevated compared with ambient CO(2). It remains
      unclear how these changes in leaf properties affect herbivory. Damage to the
      leaves of hardwood trees by herbivorous insects may be reduced in the future as
      the concentration of CO(2) continues to increase, perhaps altering the trophic
      structure of forest ecosystems.

PMID- 15948844
TI  - Links between tree species, symbiotic fungal diversity and ecosystem functioning
      in simplified tropical ecosystems.
AB  - We studied the relationships among plant and arbuscular mycorrhizal (AM) fungal
      diversity, and their effects on ecosystem function, in a series of replicate
      tropical forestry plots in the La Selva Biological Station, Costa Rica. Forestry
      plots were 12 yr old and were either monocultures of three tree species, or
      polycultures of the tree species with two additional understory species.
      Relationships among the AM fungal spore community, host species, plant community
      diversity and ecosystem phosphorus-use efficiency (PUE) and net primary
      productivity (NPP) were assessed. Analysis of the relative abundance of AM fungal
      spores found that host tree species had a significant effect on the AM fungal
      community, as did host plant community diversity (monocultures vs polycultures).
      The Shannon diversity index of the AM fungal spore community differed
      significantly among the three host tree species, but was not significantly
      different between monoculture and polyculture plots. Over all the plots,
      significant positive relationships were found between AM fungal diversity and
      ecosystem NPP, and between AM fungal community evenness and PUE. Relative
      abundance of two of the dominant AM fungal species also showed significant
      correlations with NPP and PUE. We conclude that the AM fungal community
      composition in tropical forests is sensitive to host species, and provide
      evidence supporting the hypothesis that the diversity of AM fungi in tropical
      forests and ecosystem NPP covaries.

PMID- 15948845
TI  - Phospholipase A2 up-regulation during mycorrhiza formation in Tuber borchii.
AB  - TbSP1 is a secreted and surface-associated phospholipase A(2) previously found to
      be up-regulated in C- or N-deprived free-living mycelia from the ectomycorrhizal
      ascomycete Tuber borchii. As nutrient limitation is considered an important
      environmental factor favouring the transition to symbiotic status, TbSP1 was
      suggested to be involved in the formation of mycorrhizas. An in vitro symbiosis
      system between Cistus incanus and T. borchii was set up: TbSP1 mRNA levels in
      free-living mycelia and in mycorrhizas sampled in different districts of the
      plant-fungus interaction were examined. In the same samples, TbSP1 protein
      expression was analysed by immunoelectron microscopy. A substantially enhanced
      TbSP1 mRNA expression, compared with nutrient-limited but free-living mycelia,
      was detected in the presence of the plant and reached maximal levels in fully
      developed mycorrhizas. A similar expression trend was revealed by
      immunolocalization experiments. We have shown that TbSP1 appears to respond to
      two partially overlapping yet distinct stimuli: nutrient starvation and
      mycorrhiza formation.

PMID- 15948846
TI  - Identification of perennial ryegrass (Lolium perenne (L.)) and meadow fescue
      (Festuca pratensis (Huds.)) candidate orthologous sequences to the rice Hd1(Se1)
      and barley HvCO1 CONSTANS-like genes through comparative mapping and
      microsynteny.
AB  - Microsynteny with rice and comparative genetic mapping were used to identify
      candidate orthologous sequences to the rice Hd1(Se1) gene in Lolium perenne and
      Festuca pratensis. A F. pratensis bacterial artificial chromosome (BAC) library
      was screened with a marker (S2539) physically close to Hd1 in rice to identify
      the equivalent genomic region in F. pratensis. The BAC sequence was used to
      identify and map the same region in L. perenne. Predicted protein sequences for
      L. perenne and F. pratensis Hd1 candidates (LpHd1 and FpHd1) indicated they were
      CONSTANS-like zinc finger proteins with 61-62% sequence identity with rice Hd1
      and 72% identity with barley HvCO1. LpHd1 and FpHd1 were physically linked in
      their respective genomes (< 4 kb) to marker S2539, which was mapped to L. perenne
      chromosome 7. The identified candidate orthologues of rice Hd1 and barley HvCO1
      in L. perenne and F. pratensis map to chromosome 7, a region of the L. perenne
      genome which has a degree of conserved genetic synteny both with rice chromosome
      6, which contains Hd1, and barley chromosome 7H, which contains HvCO1.

PMID- 15948847
TI  - Phylogenetic relationships among A-genome species of the genus Oryza revealed by
      intron sequences of four nuclear genes.
AB  - The A-genome group in Oryza consists of eight diploid species and is distributed
      world-wide. Here we reconstructed the phylogeny among the A-genome species based
      on sequences of nuclear genes and MITE (miniature inverted-repeat transposable
      elements) insertions. Thirty-seven accessions representing two cultivated and six
      wild species from the A-genome group were sampled. Introns of four nuclear single
      copy genes on different chromosomes were sequenced and analysed by both maximum
      parsimony (MP) and Bayesian inference methods. All the species except for Oryza
      rufipogon and Oryza nivara formed a monophyletic group and the Australian endemic
      Oryza meridionalis was the earliest divergent lineage. Two subspecies of Oryza
      sativa (ssp. indica and ssp. japonica) formed two separate monophyletic groups,
      suggestive of their polyphyletic origin. Based on molecular clock approach, we
      estimated that the divergence of the A-genome group occurred c. 2.0 million years
      ago (mya) while the two subspecies (indica and japonica) separated c. 0.4 mya.
      Intron sequences of nuclear genes provide sufficient resolution and are
      informative for phylogenetic inference at lower taxonomic levels.

PMID- 15948848
TI  - Patterns of introgression across an expanding hybrid zone: analysing historical
      patterns of gene flow using nonequilibrium approaches.
AB  - Previous studies suggest that the hybrid zone between two taxa in the Piriqueta
      caroliniana complex in central Florida (south-eastern North America) has recently
      expanded with hybrids replacing parental genotypes across a broad region of the
      Florida peninsula. Here I use patterns of genetic disequilibria and levels of
      differentiation among populations to infer historical patterns of introgression
      across this broad hybrid zone. There were strong positive associations among
      taxon-specific alleles at the southern extent of hybridization, but disequilibria
      values were close to zero across the central and northern portions of the hybrid
      zone. Levels of among-population differentiation in the central portion of the
      hybrid zone were relatively low, and increased towards the northern extent of
      hybridization. The high levels of disequilibria are coincident with the sharp
      clines at the southern end of the hybrid zone, suggesting that there is a tension
      zone in this region that is maintained by selection against hybrids and dispersal
      from parental regions. The levels of disequilibria within populations and
      patterns of differentiation among populations are consistent with historical
      introgression and northward expansion of this hybrid zone, which may have slowed
      or ceased in recent generations.

PMID- 15948849
TI  - Variation in frequency of hybrids and spatial structure among Ipomopsis
      (Polemoniaceae) contact sites.
AB  - Rates of hybridization vary among angiosperm taxa. Among-taxon variation in
      hybridization rate has been used to compare the importance of pre- and post
      zygotic reproductive isolating mechanisms. Variation in rates of hybridization
      within a single-species pair would suggest that local conditions also affect
      reproductive isolation within a single taxonomic context. In this study, contact
      sites of Ipomopsis aggregata-Ipomopsis tenuituba were surveyed for variation in
      frequency of hybrids, and spatial structure. Floral morphology was used to
      identify parent species and hybrids in seven contact sites in the western Rocky
      Mountains, USA. Contact sites varied widely in elevational range, the degree to
      which morphological variation was clinal rather than mosaic and the frequency of
      hybrids. Two sites provided a strong contrast between a clinal, unimodal site and
      a mosaic, bimodal site. This natural variation among contact sites of the same
      species pair provides an opportunity to assess the effect of local ecological
      conditions and spatial structure of parent populations on reproductive isolation,
      while controlling for between-taxon variation.

PMID- 15948850
TI  - The potential for adaptive evolution of pollen grain size in Mimulus guttatus.
AB  - We tested whether pollen grain size (PGS) shows heritable variation in three
      independent populations of Mimulus guttatus by imposing artificial selection for
      this character. In addition, we looked for correlated responses to selection in a
      range of 15 other floral characters. Heritable variation in PGS was found in all
      three populations, with heritabilities of between 19 and 40% (average 30%). After
      three generations, upward and downward lines differed on average by 30% in pollen
      volume. No consistent patterns of correlated response were found in other
      characters, indicating that PGS can respond to selective forces acting on PGS
      alone. Possible selection mechanisms on PGS in this species could include
      intermale selection, if large pollen grains produce more competitive
      gametophytes; or optimization of patterns of resource allocation, if local mate
      competition varies.

PMID- 15948851
TI  - Measuring tree root respiration using (13)C natural abundance: rooting medium
      matters.
AB  - Tree root respiration utilizes a major portion of the primary production in
      forests and is an important process in the global carbon cycle. Because of the
      lack of ecologically relevant methods, tree root respiration in situ is much less
      studied compared with above-ground processes such as photosynthesis and leaf
      respiration. This study introduces a new (13)C natural tracer method for
      measuring tree root respiration in situ. The method partitions tree root
      respiration from soil respiration in buried root chambers. Rooting media
      substantially influenced root respiration rates. Measured in three media, the
      fine root respiration rates of longleaf pine were 0.78, 0.27 and 0.18 mg CO(2)
      carbon mg(-1) root nitrogen d(-1) at 25 degrees C in the native soil, tallgrass
      prairie soil, and sand-vermiculite mixture, respectively. Compared with the root
      excision method, the root respiration rate of longleaf pine measured by the field
      chamber method was 18% higher when using the native soil as rooting medium, was
      similar in the prairie soil, but was 42% lower if in the sand-vermiculite medium.
      This natural tracer method allows the use of an appropriate rooting medium and is
      capable of measuring root respiration nondestructively in natural forest
      conditions.

PMID- 15948852
TI  - Activity profiling of ectomycorrhiza communities in two forest soils using
      multiple enzymatic tests.
AB  - Data on the diversity and distribution of enzyme activities in native
      ectomycorrhizal (ECM) communities are inadequate. A microplate multiple enzymatic
      test was developed which makes it possible to measure eight enzyme activities on
      14 individual, excised ECM root tips. Hydrolytic and oxidative enzymes are
      involved in the decomposition of lignocellulose, chitin and phosphorus-containing
      organic compounds. This test system was used to describe the functional diversity
      of ECM communities in two forest sites. This set of tests proved to be accurate
      and sensitive enough to reveal a high diversity of activity profiles, depending
      on the fungal symbiont and the soil horizon. Ectomycorrhizas can be classified
      into specialists and generalists, and appear to complement each other in the same
      horizon to collectively perform all eight activities studied. By including a
      higher number of different assays for more detailed analyses, ECM activity
      profiling will provide a valuable tool for studying the functional diversity of
      ECM communities.

PMID- 15948853
TI  - Pancreas allocation in the era of islet transplantation.

PMID- 15948854
TI  - Use of Neoral C monitoring: a European consensus.
AB  - Large-scale clinical trials using C(2) monitoring of cyclosporine (CsA)
      microemulsion (Neoral) in renal transplant recipients have demonstrated low acute
      rejection rates and good tolerability with a low adverse event profile in a
      variety of settings: with or without routine induction therapy; in combination
      with mycophenolate mofetil; with standard-exposure or low-exposure Neoral; and in
      patients with immediate or delayed graft function. In liver transplantation, C(2)
      monitoring significantly reduces the severity and incidence of acute rejection
      compared with C(0) monitoring, without adverse consequences in terms of renal
      function or tolerability. Different C(2) targets are appropriate depending on
      adjunctive immune suppression, level of immunologic risk, CsA tolerability, risk
      of renal toxicity and time since transplantation. CsA absorption may increase
      substantially in most patients during the first 1-2 weeks post-transplant, and
      this should be taken into account to avoid overshooting C(2) target range. A
      patient with a low C(2) value may be either a low or a delayed absorber of CsA,
      or be a normal absorber who is receiving too low a dose of Neoral. C(2)
      monitoring alone is insufficient to differentiate between these types of
      patients, and measurement of additional timepoints is recommended. Adopting C(2)
      monitoring in maintenance transplant patients identifies those who are
      overexposed to CsA. In summary, randomized, prospective, multicenter studies and
      single-center trials have evaluated Neoral C(2) monitoring within a range of
      regimens in different organ types, providing a robust evidence base for the
      benefits of this sensitive monitoring technique.

PMID- 15948855
TI  - Prevalence of cancer history prior to renal transplantation.
AB  - Recurrent and de novo cancers contribute to morbidity and mortality post
      transplantation. However, data on cancer prevalence in waiting list patients are
      lacking. The purpose of this study was to determine the prevalence of malignancy
      in patients considered for renal transplantation. Records of 382 potential renal
      transplant recipients were reviewed for the presence of malignant tumours. In 38
      patients 45 tumours were detected. Forty-two malignancies were histologically
      confirmed, in three patients the evaluation was ongoing. Fourteen tumours were
      diagnosed before and 31 after initiation of dialysis. Overall cancer prevalence
      was 9.9%. For patients in the waiting list, the mean time from diagnosis of the
      malignancy was 2.2 years. Twenty of 45 (44%) tumours were located in the urinary
      system. The majority of malignancies was treated with a curative intention. Thus,
      68% of patients with malignancies were listed as 'transplantable' or 'temporarily
      not transplantable'. From the waiting list, 13% were removed , 8% died and 11%
      had their evaluation halted because of their malignancy. Four patients received a
      transplant while eight patients died or were removed permanently from the list
      prior to transplantation. Death or removal from the list was as frequently
      related to tumour progression as to other causes (four patients each). A
      substantial number of waiting list patients had a history of malignancy. Future
      strategies have to identify patients at risk to assure intensive monitoring for
      recurrence, selection of patients who do not benefit from deferred
      transplantation and consideration of specific immunosuppressive protocols.

PMID- 15948856
TI  - Impact of pretransplant dialysis on early graft function in pediatric kidney
      recipients.
AB  - Delayed graft function (DGF) is a frequent complication of kidney transplantation
      (KT) that may affect both short- and long-term graft outcome. It has been
      reported that pretransplantation peritoneal dialysis was correlated with a better
      recovery of graft function than hemodialysis in adult kidney recipients. However,
      the effect of pretransplantation dialysis mode (PDM) seemed to be unclear on the
      early outcome of KT in pediatric recipients. In this study, the potential impact
      of PDM on early graft function was evaluated in 174 pediatric patients who
      underwent KT by using cadaveric donors. The primary outcome parameter was the
      time to reach a serum creatinine (SCr) level 50% of the pretransplantation value
      [T(1/2(SCr))], while DGF was defined as a T(1/2(SCr)) >3 days after KT (n = 40).
      By stratifying kidney recipients for normal function graft or DGF, this latter
      group showed a significantly higher body weight (BW) on the day of KT (P =
      0.014), body surface area (BSA) (P = 0.005), warm ischemia time (WIT) (P =
      0.022), early SCr on the day 1 after KT (P < 0.001), and T(1/2(SCr)) (P < 0.001),
      whereas lower urine volume (UV) collected in the first 24 h after KT (P < 0.001)
      and fluid load (P < 0.001) occurred. Univariate exponential correlation that was
      carried out between T(1/2(SCr)) and all the other variables had shown a better
      value than the linear correlation for BW (R(2) = 0.28 vs. R(2) = 0.04), BSA (R(2)
      = 0.29 vs. R(2) = 0.03), and SCr (R(2) = 0.51 vs. R(2) = 0.28). In a multivariate
      regression analysis performed by entering T(1/2(SCr)) as dependent variable and
      following a forward stepwise method, cold ischemia time (CIT) (P = 0.027) but not
      PDM (P = 0.195) reached significance. In a Cox regression analysis carried out
      with T(1/2(SCr)) as dependent variable, neither CIT nor PDM gained significance.
      This study suggests that PDM does not affect early graft function in pediatric
      kidney recipients.

PMID- 15948857
TI  - Living donor liver transplantation for primary biliary cirrhosis: retrospective
      analysis of 50 patients in a single center.
AB  - Summary Although living donor liver transplantation (LDLT) is accepted as an
      alternative therapy for primary biliary cirrhosis (PBC), the postoperative
      results are not well known. Fifty patients with PBC underwent LDLT at Tokyo
      University Hospital. Their clinical records were retrospectively analyzed.
      Postoperative death occurred in four patients within 2 months (mortality, 8%),
      while later death occurred in three patients. In the median follow-up period of
      35 months (range 4-84 months), the 1, 3, and 5-year overall survival rates were
      90%, 88%, and 80%, respectively. The laboratory data indicated that graft
      function was sufficient. No recurrence of PBC was confirmed. Multivariate
      analysis indicated that an updated Mayo score of <10 was a significantly
      favorable factor for short hospitalization (hazard ratio, 9.52; 95% confidence
      interval, 1.14-79.5; P = 0.03). In conclusion, LDLT provides a satisfactory long
      term survival with the PBC patients.

PMID- 15948858
TI  - C4d peritubular capillary staining in chronic allograft nephropathy and
      transplant glomerulopathy: an uncommon finding.
AB  - The true incidence of positive C4d staining in the peritubular capillaries of
      biopsies with chronic allograft nephropathy (CAN) and transplant glomerulopathy
      (TGP) remains controversial. We retrospectively reviewed all transplant biopsies
      performed at Saint Louis University Hospital between June 2002 and May 2004. We
      examined the incidence of positive C4d staining in the peritubular capillaries of
      biopsy specimens with pure CAN with or without features of TGP. We identified 54
      biopsies in 43 patients showing CAN. The average age was 46 +/- 13 years. The
      average creatinine at the time of biopsy was 308 +/- 211 micromol/l (3.5 +/- 2.4
      mg/dl). Twenty (37%) biopsies exhibited features consistent with TGP. Only two
      biopsies had positive C4d staining in the peritubular capillaries. The C4d
      positive biopsies were from two different patients; one patient had donor
      specific antibodies (DSA) against HLA class 1 at the time of biopsy and the other
      patient had no detectable DSA. None of the TGP biopsies showed peritubular C4d
      staining. C4d staining of the peritubular capillaries appears to be rare in
      patients with pure CAN with and without TGP features.

PMID- 15948859
TI  - Cyclosporine dose reduction in stable renal transplant patients with high C2
      level: simplified method of single C2 measurement and individualization of C0
      target.
AB  - It is recommended that cyclosporine dosing should be based on the whole blood
      level 2 h after a dose (C2), not the trough level (C0). Initial studies did not
      however establish the outcome of dosing according to C2 levels in long-term
      patients previously managed by C0 levels. C0 and C2 were measured in 152 stable
      patients receiving Neoral therapy, mean 86.9 months after transplantation. This
      showed that 38 (25%) had C2 levels above a target range of 700-900 microg/l.
      Higher C2 levels were associated with higher cholesterol levels (P = 0.0058) and
      higher diastolic blood pressure (P = 0.0163). Cyclosporine dose reduction was
      undertaken in 32 patients with high C2 levels. For logistical reasons, C2 was not
      performed regularly, but an individualized C0 level was set for each patient. A
      16% reduction in mean cyclosporine dose was achieved, associated with a 28% fall
      in mean C0, from 212 to 153 microg/l, and a 25% fall in mean C2, from 1075 to 820
      microg/l. There was no excess in adverse events in the dose reduction cohort,
      compared with patients with initial C2 levels <900 microg/l. Over a mean 15 month
      follow-up period in the dose reduction cohort, there was a 4.4% reduction in mean
      diastolic blood pressure, from 84.9 (SEM 2.1) to 80.2 (1.9) mmHg, P = 0.023; and
      a 10.4% reduction in mean cholesterol, from 5.71 (0.27) to 5.11 (0.25), P = 0.005
      (patients starting on statin during follow-up excluded). In patients with initial
      C2 <900 microg/l, blood pressure did not fall and the cholesterol fell by 3.9%,
      from 5.27 (0.14) to 5.07 (0.15) mmol/l (P = 0.0405). In conclusion, cyclosporine
      dose reduction was safe in stable long-term renal allograft recipients with high
      C2 levels. There was an improvement cholesterol levels and a small improvement in
      blood pressure after cyclosporine dose reduction.

PMID- 15948860
TI  - Left and right lobe split-liver transplantation for two paediatric recipients
      from a 9-year-old donor.
AB  - Liver splitting increased the number of grafts for paediatric recipients. Usually
      the two left lateral segments are given to a child and the remaining liver to an
      adult recipient. Splitting into a right and a left lobe may allow a small adult
      to benefit from the left lobe while the right lobe goes to another adult
      recipient. Splitting of paediatric grafts, however, has rarely been performed. We
      here report on a case where the liver from a 9-year-old donor was ex situ split
      along the principal fissure creating a right and left lobe which provided grafts
      for two children aged 2 and 3 years. Immunosuppression consisted of Tacrolimus
      based triple drug therapy. Recovery was completely uneventful in both children
      who are alive and well with normally functioning grafts 11 months following
      transplantation. These cases demonstrate the feasibility of splitting even
      paediatric grafts for two small children.

PMID- 15948861
TI  - Open prospective multicenter study of conversion to tacrolimus therapy in renal
      transplant patients experiencing ciclosporin-related side-effects.
AB  - The hyperlipidemic and hypertensive effects of ciclosporin constitute a
      cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality
      of life. This was a 6-month, open, prospective, multicentre study in 296 adult
      kidney transplant patients to evaluate the conversion from ciclosporin to a
      tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia
      (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia
      (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately
      improved in 59.1% and 63.5% of patients, and strongly or completely resolved in
      29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely
      resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255
      to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5
      mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin
      related side-effects resolved or improved after conversion to tacrolimus.

PMID- 15948862
TI  - Clinical outcome of cadaveric renal allografts contaminated before
      transplantation.
AB  - This analysis was performed to define the incidence of pretransplant microbial
      contamination of donor kidneys, and to assess the resultant morbidity including
      infections requiring therapy, and graft loss. Case records of all 638 renal
      allograft recipients patients transplanted in our centre during the period June
      1990 to October 2000 were studied. All the recipients were given a single dose of
      intravenous antibiotics at the time of induction of anaesthesia. A total of 775
      microbiology reports on perfusion fluid, kidney swabs and ureteric tissue were
      retrieved. Fifty-eight of 638 (9.1%) patients were transplanted with a graft that
      showed preoperative contamination. 18 of these 58 patients (31%) subsequently
      required antibiotic treatment. Thirty of 32 patients who received kidney
      contaminated with skin flora had a benign course (i.e. no unexplained, no
      positive blood cultures or graft infection). By contrast, seven of nine
      recipients with grafts whose perfusion fluid yielded lactose fermenting coliforms
      (LFCs) required antibiotics and three of nine of them suffered graft loss as a
      result. Two of these patients had bacteraemia caused by LFC, and one died. Three
      of five patients with positive cultures due to yeast required treatment with
      antifungals. None of the four patients who had graft contaminated by
      Staphylococcus aureus became infected. One-year 49/58 (85%) of these patients
      survived with functioning graft. Overall 1-year patient survival was 53/55 (92%).
      These data suggest that contamination of renal allografts by LFCs or yeasts need
      to be treated preemptively before the onset of clinical manifestations. By
      contrast, contamination with skin contaminants does not pose a risk to the graft.

PMID- 15948863
TI  - Current practices of donor pancreas allocation in the UK: future implications for
      pancreas and islet transplantation.
AB  - Recent refinements in technique mean islet cell transplantation offers the chance
      of a cure to an increasing patient cohort with diabetes. Such developments put
      pressure upon the scarce resource of donor organs, with potential competition
      between the modalities of cellular and solid organ transplantation. This
      questionnaire based study examines current patterns of donor pancreas procurement
      and use. Reasons for non procurement are studied together with the attitudes of
      transplant professionals to pancreas allocation. The minority of potentially
      useful pancreata are currently made available to either whole pancreas or islet
      transplant programs. Whilst professionals appreciate the role of each modality,
      there is a need to define criteria for pancreas allocation to avoid under use of
      donor organs.

PMID- 15948864
TI  - OKT3 and ganciclovir treatments are possibly related to the presence of Epstein
      Barr virus in serum after liver transplantation.
AB  - The development of Epstein-Barr virus (EBV) associated lymphoproliferative
      disorder (PTLD) is related to EBV genome numbers in serum or plasma and B-cells,
      and the level of immunosuppression. EBV DNA viremia, defined as presence of EBV
      genomes in serum or plasma, is common in immunodeficiency. This survey of EBV
      viremia was performed by real-time polymerase chain reaction (PCR) on consecutive
      serum samples of 21 patients with acute (n = 3) or chronic liver disease (n = 18)
      during the first year after liver transplantation (LTX). Cytomegalovirus (CMV)
      DNA was analyzed with PCR in serum or leukocytes. The levels of EBV and CMV
      viremia were related to PTLD and the effect of different anti-rejection regimens.
      All patients were EBV-seropositive pre-LTX. In total, 24 of 152 (16%) samples
      from 10 of 21 (48%) individuals were EBV positive [five of 11 cyclosporin A
      (CsA); five of 10 tacrolimus treated cases]. EBV viremia was demonstrated in five
      of seven patients with OKT3 therapy. The number of EBV DNA positive samples was
      highest (26%) at 14 days after LTX. In the OKT3 treated groups, the medians of
      EBV DNA copy numbers were 1600/ml (range 230-7200) and 380/ml (range 120-860) in
      the CsA and tacrolimus patients, respectively (P < 0.02). One patient developed
      EBV lymphoma and another one EBV hepatitis 13 months and 24 days post-LTX,
      respectively. Both patients had received OKT3. Their EBV genome load was not
      significantly different from what was found in other patients. After ganciclovir
      therapy, EBV DNA was eradicated from serum in four of five patients for several
      months. EBV DNA load was not affected by CMV infection or disease. We conclude
      that presence of EBV in serum is a possible marker of an active infection and an
      early ganciclovir therapy may be beneficial. Quantification of EBV load offers
      the potential to implement pre-emptive interventions.

PMID- 15948865
TI  - MCI-186 (edaravone), a free radical scavenger, attenuates hepatic warm ischemia
      reperfusion injury in rats.
AB  - Hepatic warm ischemia-reperfusion injury (IRI) during hepatectomy and liver
      transplantation is a major cause of liver dysfunction in which the pathologic
      role of free radicals is a major concern. To assess the effect of MCI-186
      (edaravone) on hepatic IRI, male Wistar rats were subjected to partial hepatic
      ischemia for 60 min after pretreatment with vehicle (group C) or MCI-186 (group
      M), or after both MCI-186 pretreatment and additional administration of MCI-186
      12 h after reperfusion (group MX). Groups M and MX showed significantly lower
      levels of serum alanine aminotransferase and hepatic lipid peroxidation than
      group C, and also significantly lower expression levels of mRNA for cytokines,
      chemokines and intercellular adhesion molecule-1. There were fewer tissue
      monocytes and neutrophils in groups M and MX than in group C. These effects were
      more marked in group MX than in group M. Our findings suggest that treatment with
      MCI-186 attenuates hepatic IRI in this rat in vivo model.

PMID- 15948867
TI  - Ultrastructural analysis of the Fisher to Lewis rat model of chronic allograft
      nephropathy.
AB  - Chronic allograft nephropathy (CAN) is the leading cause of graft loss following
      kidney transplantation. One factor contributing to CAN is chronic alloimmune
      injury. However, the involvement of alloantigen-dependent and -independent
      factors in CAN is unclear. The pathomechanism of CAN has been extensively studied
      by utilizing the Fischer-to-Lewis (F344-to-LEW) rat model. Transplant
      capillaropathy (circumferential multiplication of the peritubular capillary
      basement membrane) and transplant glomerulopathy (reduplication of the glomerular
      basement membrane) have recently been validated clinicopathologically as
      ultrastructural indicators of chronic alloimmune injury. To investigate the
      presence of these markers, F344-to-LEW kidneys were examined by electron and
      light microscopy 32, 40 and 52 weeks after implantation. F344 rats with or
      without 30-min ischemia of the left kidney following right nephrectomy served as
      controls. All transplanted rats displayed marked proteinuria. On electron
      microscopy, transplant capillaropathy, transplant glomerulopathy, and T-cell
      cytotoxicity (indicator of ongoing cellular rejection) were absent. On light
      microscopy, the arteries were devoid of intimal fibrosis. Focal-segmental
      glomerulopathy resembling hyperfiltration injury was encountered, with mild
      interstitial infiltration, fibrosis, and tubular atrophy. The proteinuria and
      kidney pathology were more severe in transplanted than in ischemic or
      uninephrectomized rats. Because chronic-active rejection could not be detected
      between weeks 32 and 52, we propose that the alloantigen-dependent initial graft
      injury subsides, but induces the late events: glomerular hyperfiltration,
      proteinuria, and glomerulosclerosis. Accordingly, the model - in the late phase -
      is suitable to investigate alloantigen-independent factors of CAN and lacks
      markers of alloantigen-dependent processes.

PMID- 15948866
TI  - Corneal rat-to-mouse xenotransplantation and the effects of anti-CD4 or anti-CD8
      treatment on cytokine and nitric oxide production.
AB  - Corneal xenotransplantation may be an alternative approach to overcome shortage
      of allografts for clinical transplantation. Orthotopic corneal rat-to-mouse
      xenotransplantation and syngeneic transplantation was performed and the effects
      of anti-CD4 and anti-CD8 treatments on corneal xenograft survival and production
      of cytokines, interleukin (IL)-2, IL-4, IL-10, gamma-interferon (IFN-gamma) and
      nitric oxide (NO) were evaluated. RT-PCR was used to determine the expression of
      genes for cytokines and inducible nitric oxide synthase (iNOS) in the grafts. The
      presence of iNOS protein in grafts was detected by immunofluorescent staining. We
      found that corneal xenotransplantation was associated with a strong upregulation
      of genes for both Th1 and Th2 cytokines and with NO production in the graft.
      Treatment of xenograft recipients with mAb anti-CD4, but not anti-CD8, resulted
      in a profound inhibition of IL-2, IL-4 and IL-10 production, and in a significant
      prolongation of corneal xenograft survival. The results show that upregulation of
      Th2 cytokines after corneal xenotransplantation does not correlate with xenograft
      rejection. Rather, corneal graft rejection is associated with the expression of
      genes for IFN-gamma and iNOS and with NO production.

PMID- 15948868
TI  - Cyclosporine decreases prostaglandin E2 production in mouse medullary thick
      ascending limb cultured cells.
AB  - Intrarenal vasoconstriction is thought to be the major pathogenesis of
      cyclosporine (CsA) nephrotoxicity. Nitric oxide (NO) and prostaglandin E2 (PGE2)
      are two of the major intrarenal vasodilators, which protect kidney from ischemia.
      CsA inhibited NO production in renal epithelial cells. The interaction between
      CsA and intrarenal PGE2 and NO production is still unclear. The aim of the study
      is to evaluate the interaction of CsA with intrarenal PGE2 and NO production in
      renal epithelial cells. Models of cultured mouse thick ascending limb (TAL) cells
      are chosen to perform the experiments, as TAL cells are the major site of
      intrarenal PGE2 production and target of CsA nephrotoxicity. We investigated the
      PGE2 production by enzyme-linked immunosorbent assay, and cyclooxygenase (COX-1
      and COX-2) mRNA expression by RT-PCR in cultured cells treated with or without
      CsA. TAL cells maintained the main characteristics of their parental cells. TAL
      cells produce PGE2 mainly by COX-1 in steady state and by COX-2 in stimulated
      state by lipopolysaccharide (LPS). CsA (100 ng/ml) significantly reduced the PGE2
      production up to 43% in TAL cells in LPS stimulated status (control versus CsA:
      375.1 +/- 15.5 vs. 187.2 +/- 12.2 nm/mg protein, n = 7, P < 0.001). The effects
      were dose-dependent. The mRNA expression of COX1 is not affected and COX-2 is
      decreased in CsA-treated TAL cells. NO donor could prevent the inhibitory effects
      of CsA. We concluded that CsA decreased intrarenal PGE2 production in stimulated
      status mainly by decreasing COX-2 expression. NO might play a role in the CsA
      effect. The results suggested the role possible of PGE2 in CsA nephrotoxicity.

PMID- 15948869
TI  - Successful treatment with tenofovir in a child C cirrhotic patient with
      lamivudine-resistant hepatitis B virus awaiting liver transplantation. Post
      transplant results.
AB  - Antiviral treatment can be complex in decompensated hepatitis B virus (HBV)
      cirrhosis because of potential emergence of lamivudine-resistant mutants and
      worsening liver function, and to multifactorial nephrotoxicity. Negative HBV-DNA
      status by hybridization before liver transplantation is a favorable prognostic
      factor. We present the case of a 54-year-old HBV+ liver transplantation candidate
      who, after testing negative for HBV-DNA, developed YMDD lamivudine-resistant
      mutants resulting in a deteriorated clinical condition. After 8 months of
      adefovir plus lamivudine double therapy, only partial response was achieved.
      Tenofovir was added to this regimen, and an early decline of HBV-DNA was seen at
      4 weeks without adverse events. The patient underwent transplantation. At 21
      month postoperative follow-up, the patient's outcome was excellent. Post
      transplantation HBV prophylaxis, taking into account the prior development of
      mutants, consists of hepatitis B immunoglobulin plus lamivudine and adefovir.
      Tenofovir was well tolerated and produced a fast antiviral response, suggesting
      its potential value in combined antiviral treatment for liver transplantation
      candidates.

PMID- 15948870
TI  - Kidney transplantation with two donor ureters in patient with previous
      ileogastric conduit.
AB  - The purpose of our publication is to focus upon the technical aspects of a rare
      combination of kidney transplant with two donor ureters in a patient with
      neurogenic bladder and previous reconstruction of a continent ileogastric
      conduit.

PMID- 15948871
TI  - Endovascular treatment of aortic pseudoaneurysm after liver transplantation.

PMID- 15948872
TI  - Living donor liver transplantation for recurrent hepatocellular carcinoma.

PMID- 15948873
TI  - Lung transplantation for acute respiratory failure in rapidly progressive
      idiopathic pulmonary fibrosis.

PMID- 15948874
TI  - Mothers' voice: a qualitative study on feeding children with cerebral palsy.
AB  - BACKGROUND: Around one third of children with cerebral palsy have severe
      difficulty eating and drinking and are at risk of undernourishment. A gastrostomy
      feeding tube may be offered as a way of providing nourishment as it bypasses the
      main physical difficulties. For the families feeding and concerns about the
      method of feeding affect many areas of their daily life but we know little about
      what the experience is actually like. This study aimed to explore mothers'
      experience of feeding children with cerebral palsy. METHODS: Ten principal carers
      for children with cerebral palsy and severe eating difficulty were interviewed.
      Four of the children, one girl and three boys aged 2.5 to 4.5 years were being
      fed solely by mouth and six children, three girls and three boys, aged 4.5 years
      to 15 years and 10 months, were fed via a gastrostomy feeding tube. Long, loosely
      structured tape recorded interviews were transcribed and manually analysed using
      a phenomenological approach. This involved extracting and coding each relevant
      phrase that contained meaning; then through sequential stages of ordering and
      reduction into themes the invariant meanings were uncovered. The transcripts were
      analysed in two groups, oral and gastrostomy feeding, in an identical manner.
      RESULTS: Phenomenological analysis resulted in two prose accounts that described
      in depth the essence of the experience. The accounts were mutually informative.
      Both groups treasured feeding by mouth suggesting that support for oral feeding
      should be given a higher priority. The accounts explained why some professional
      encounters added to families' stress and why consistency of care is so important.
      The study gives insight about the kinds of support families find helpful.
      CONCLUSIONS: This study should help those involved to understand the families'
      predicament better and so make a contribution towards providing more appropriate
      support.

PMID- 15948875
TI  - Parents' perspectives on coping with Duchenne muscular dystrophy.
AB  - BACKGROUND: The author, who has a grown son with Duchenne Muscular Dystrophy
      (DMD), has personally experienced a lack of available information for parents
      about coping with DMD. Therefore, as a longtime personal goal, she developed this
      study to address that lack of information. METHODS: Fifteen semi-structured
      interviews were conducted with 23 parents (n = 7 with both parents; n = 1 with
      two sisters; n = 6 with mothers only; n = 1 with father only). The purpose of the
      interviews was to examine the strategies parents use to cope when their sons have
      DMD. The interviews were conducted in 12 states, taped and transcribed. RESULTS:
      Grounded theory analysis of the interview data indicated the willingness of these
      parents to share information to empower others like themselves. CONCLUSIONS:
      Parents want to be heard and valued as experts on DMD by medical and other
      professionals who interact with their sons. In addition, they want to proactively
      participate in their sons' lives and to encourage other parents to do the same.

PMID- 15948876
TI  - Child or family assessed measures of activity performance and participation for
      children with cerebral palsy: a structured review.
AB  - BACKGROUND: There is a need to measure children's 'activity performance and
      participation' as defined in the World Health Organization's International
      Classification of Functioning, Disability and Health for Children and Youth (WHO
      ICF). The aim of this review is to identify instruments that are suitable for use
      in postal surveys with families of children with cerebral palsy. METHODS: We
      conducted a structured review of instruments that use child or family self
      assessment of 'activity performance and participation'. The review involved a
      systematic search for instruments using multiple published sources. Appraisal of
      the instruments used the predefined criteria of appropriateness, validity,
      reliability, responsiveness, precision, interpretability, acceptability and
      feasibility. RESULTS: There are relatively few child or family assessed
      instruments appropriate for measuring children's activities and participation.
      Seven instruments were identified that could potentially be administered by mail.
      The Assessment of Life Habits for Children (LIFE-H) was the most appropriate
      instrument as assessed by its content but the reliability of child or family self
      assessment is not known. If the LIFE-H were shown to be a reliable self-report
      measure then the LIFE-H would be the recommended choice. Currently, the
      Activities Scale for Kids and the condition-specific Lifestyle Assessment
      Questionnaire for cerebral palsy (LAQ-CP) provide the broadest description of
      what and how frequently children with cerebral palsy perform a range of
      activities and thereby indicate participation. The LAQ-CP also provides
      additional contextual information on the impact of any disability on the
      participation of the family unit. CONCLUSION: There remains much scope for
      developing valid and reliable self-assessed measures corresponding to the WHO ICF
      dimensions of activities and participation.

PMID- 15948877
TI  - Development of a measure of the health-related quality of life of children in
      public care.
AB  - OBJECTIVES: To validate PedsQL for children in public care and develop an 'in
      care' module. DESIGN AND SETTING: Questionnaire development and validation.
      Questionnaires were completed in placement. A total of 69 children in public care
      (aged 8-18 years) and their carers were recruited through routine paediatric
      assessments, and 662 children not in public care were recruited from local
      schools. MEASURES: Self- and proxy-report versions of PedsQL generic module and
      the 'in-care' module. RESULTS: Cronbach's alpha for the generic module ranged
      from 0.66 to 0.88 and from 0.74 to 0.90 for self- and proxy-report respectively.
      Lower scores were reported for children in care compared with peers living at
      home for proxy- and self-report. Proxy- and self-report correlation ranged from
      0.43 to 0.60 (P < 0.001). Cronbach's alpha for the in-care module was 0.87 and
      0.91 for self- and proxy-report respectively. Proxy- and self-report scores
      showed significant correlation with generic module scores. The highest
      correlations were seen with sub-scales measuring Psychosocial Functioning (e.g.
      Emotional Functioning: Pearson's r = 0.67 and 0.59, P < 0.001 for self- and proxy
      report respectively). Proxy- and self-report correlation was 0.45 (P < 0.001).
      CONCLUSIONS: We found PedsQL generic module and the newly developed 'in-care'
      module to have excellent internal reliability for self- and proxy-report.
      Validity was established for both measures and significant correlation found
      between child and proxy ratings. Although further testing of the measures is
      recommended, both have potential value in assessing the success of placements and
      could provide a reliable and valid tool for individual patient analysis in
      clinical practice and for research with this group.

PMID- 15948878
TI  - Feeding practices in 105 counties of rural China.
AB  - BACKGROUND: China has the largest population in the world with more than 70% of
      the people living in rural areas. Over 34% of children under the age of 5 years
      are responded to show moderate or severe growth stunting, so United Nations
      International Children's Emergency Fund and Chinese Ministry of Health conducted
      this large-scale survey in China. This study aimed to learn the feeding practice,
      to find the problems in child-feeding practice and to provide evidence for the
      government to develop an approach to child malnutrition in rural China. METHODS:
      A structured questionnaire was used to survey 21,036 mothers of children with age
      of 0-24 months. RESULTS: Of the 20,915 children, 98.22% were breastfeeding and
      24.36% were exclusively breastfeeding. The proportion of children with weekly
      protein intake was 78.47%. Among the infants under 4 months, the risk of
      pneumonia in the group of exclusive breastfeeding was 1.69%, while in the group
      of non-exclusive breastfeeding was 3.63%, showing a statistically significant
      difference between the two groups. The risk of diarrhoea in the group of
      exclusive breastfeeding and in the group of non-exclusive breastfeeding among the
      infants under 4 months was 24.37% and 40.86%, respectively, also showing a
      statistically significant difference between the two groups. For children with
      age 4-6 months, the complementary feeding contributed to a higher prevalence of
      diarrhoea, but not pneumonia. CONCLUSIONS: The breastfeeding was very common, but
      the exclusive breastfeeding was quite low and the exclusive breastfeeding for
      children under the age of 4 months decreased the risks of pneumonia and
      diarrhoea. For children with age 4-6 months, the exclusive breastfeeding could
      decrease the risk of diarrhoea, too. Protein intake was insufficient for children
      in rural China. The rural people lacked health knowledge and were greatly
      influenced by traditional feeding practices.

PMID- 15948879
TI  - Clinical, socio-demographic, neurophysiological and neuropsychiatric evaluation
      of children with volatile substance addiction.
AB  - BACKGROUND: Abuse of organic volatile substances in children has become a social
      health problem that is increasing in the recent years. Among these substances,
      toluene is highly preferred by abusers because of its euphoric effect, cheapness
      and easy availability. There is no published research on the clinical and
      neurophysiological evaluation of children with short-term volatile substance
      addiction. METHODS: In this study, socio-demographic characteristics were
      questioned in 12 children with a mean age of 15 years and a duration of toluene
      abuse for a mean of 2.3 years, and the clinical characteristics of central and
      peripheral nervous system damage caused by volatile substances, particularly by
      toluene were analysed, and probable neurological disorders were investigated by
      means of neurophysiological and neuropsychological tests. All tests were compared
      with a control group. RESULTS: Fifty-eight percent of the children included in
      the study had pathological findings in the neurological examination. There was
      pyramidal involvement in 25% and peripheral nerve involvement in 33.3% of the
      cases. Evaluation of the cognitive functions revealed 33.3% pathology in the
      'Short Test of Mental Status' which assesses functions of orientation, attention,
      learning, arithmetic calculation, abstraction, information, construction and
      recall. Sensorial polyneuropathy was found in 33.3% of the cases in nerve
      conduction studies. Somatosensory-evoked potentials revealed pathology in 16.7%
      of the cases and brainstem-evoked potentials in 50% of the cases. No pathology
      was observed in electroencephalography and visual-evoked potentials. CONCLUSION:
      In our study, neurophysiological and neuropsychiatric tests revealed that toluene
      causes slow progressive, clinical and subclinical central and peripheral nerve
      damage. In Turkey, because of cheapness, easy availability and legal use of
      volatile substances, the clinical extent of systemic and neurological toxicity of
      volatile substance abuse is increasing. Abuse of volatile substances, a currently
      increasing social issue, may create important physical problems which can be
      permanent.

PMID- 15948880
TI  - Associations of lifestyle factors with quality of life (QOL) in Japanese
      children: a 3-year follow-up of the Toyama Birth Cohort Study.
AB  - PURPOSE: To examine the associations between lifestyle factors and quality of
      life (QOL) among Japanese children. METHODS: Participants were 7794 children
      (3869 boys and 3925 girls) aged 9-10. They completed a questionnaire regarding
      lifestyles at baseline survey and were followed up for 3 years. In the follow-up
      survey, QOL was evaluated using a Japanese version of the COOP charts. Children
      rated their QOL as one of five response categories. Subjects rated as 'very well'
      or 'pretty good' were considered to have good QOL, and the remainder was assumed
      to have poor QOL. Logistic regression analysis was performed to evaluate the
      relationship between lifestyles or changes in lifestyles and QOL. In the
      multivariate analysis model, age, sex, body mass index (BMI), and lifestyle
      factors were simultaneously entered. RESULTS: During the follow-up period,
      children became more sedentary. Compared to children participating in physical
      activity 'very often' at baseline, those who exercised 'almost never' were more
      likely to have poor QOL [OR (95% CI): 1.92 (1.26-2.93)]. Children who developed
      or maintained undesirable lifestyles had high OR for poor QOL. Compared to
      children taking breakfast 'often' during the follow-up period, those changing
      from 'often' to 'seldom' or those taking breakfast 'seldom' were more likely to
      have poor QOL [1.61 (1.24-2.07), 2.05 (1.03-4.09), respectively]. When compared
      with children maintaining their participation in physical activity 'often', those
      who changed from 'often' to 'seldom' and those who kept 'seldom' were more likely
      to have poor QOL [2.10 (1.84-2.39), 2.21 (1.88-2.59), respectively]. CONCLUSIONS:
      This study shows that unfavourable lifestyles in childhood are associated with
      poor QOL in early adolescence. Early intervention could be worth considering to
      keeping desirable lifestyles during childhood.

PMID- 15948881
TI  - The secular trends in height and weight of Turkish school children during 1993
      2003.
AB  - BACKGROUND: Secular changes in growth and development can be considered as the
      changing pattern of somatic development of children in a particular population
      from one generation to another. Developing countries, which have many changes in
      socio-economical conditions, reveal various trends in growth. The aims of this
      study were to analyse growth trends in weight and height of Turkish children from
      a school in Ankara over the period 1993-2003 with 10-year time interval, and to
      determine the relation between secular trends. METHODS: Anthropometric
      measurements of 1214 children and adolescents (611 boys and 603 girls) aged
      between 7 and 15 years from Ankara, Turkey, obtained cross sectionally in 2003
      were compared with measurements of 867 school children (451 boys and 416 girls)
      from a previous study which had been obtained in the same primary school in 1993.
      For 7-15 years of age the increments of weight and height were determined, and
      analysed statistically. RESULTS: In 2003 survey boys and girls were taller and
      heavier than their peers from previous study in all age groups. For all cohorts
      in boys from 7 to 15 years, weight increments between 2.7 and 6.3 kg/decade and
      height increments between 1.7 and 5.5 cm/decade were demonstrated. For girls in
      the same cohorts, weight increments between 2.8 and 6.5 kg/decade and height
      increments between 1.8 and 5.7 cm/decade were indicated. Both weight and height
      increments suggest an upward displacement of growth curves in this interval of 10
      years. CONCLUSION: A significant secular increase in weight and height
      measurements were found in 7-15-year-old boys and girls in Ankara. These secular
      increases can be explained with improvements in social and health indicators that
      reflect the overall health status of the population. The secular increases in
      growth of Turkish school children may reveal updates of growth standards.

PMID- 15948882
TI  - Getting the run around: accessing services for children with developmental co
      ordination disorder.
AB  - BACKGROUND: Accessing services for children with developmental co-ordination
      disorder (DCD) is frequently difficult for parents who have to navigate both
      health and education systems to find a diagnosis and appropriate interventions.
      METHOD: A qualitative study design incorporating a phenomenological perspective
      was utilized to understand the nature of the experiences of these parents in
      attempting to access support for their children with DCD. Twelve parents, whose
      children attended the Kids Skills Clinic at the University of Western Ontario and
      were identified as having DCD, were interviewed by the second author. Interviews
      were transcribed verbatim and analysed using constant comparative method. Member
      checking, peer checking and code-recoding were carried out to enhance rigour in
      data analysis. RESULTS: A number of themes emerged focusing on the common
      problems experienced leading to occupational therapy referral. Parents' journeys
      to seek and access services for their children with DCD were characterized by a
      sense of maternal knowing, experience of frustration, trivialization of the
      problem, a sense of 'going it alone', and 'getting the run around'. CONCLUSIONS:
      Implications for health and educational professionals working with children, in
      terms of recognition of DCD and referral for services, are described.

PMID- 15948883
TI  - Young adolescents' perceptions of peer sexual behaviours: the role of television
      viewing.
AB  - OBJECTIVE: To investigate whether young adolescents' perceptions of peers' sexual
      activity is related to the amount of television viewing, and whether this
      relationship may be moderated by young adolescents' pubertal development.
      METHODS: This study used a sample of 12- and a sample of 15-year-olds; 2127
      respondents in a targeted sample of nine schools in Flanders (the Dutch-speaking
      part of Belgium), completed a questionnaire with questions about their television
      viewing behaviour, the estimated prevalence of given sexual activities in peers,
      and self-reports on pubertal development and sexual experience. RESULTS: In the
      sample of 12-year-olds, results demonstrated that a quadratic regression equation
      provides the best description for the relationship between television viewing and
      perceptions of peer sexual behaviours, indicating that the 'effect' of television
      only starts off after a level of about 45 h of television viewing per week.
      Further exploration showed that this relationship remains significant when
      controlling for gender and sexual experience, and is stronger at more advanced
      levels of pubertal development. In the sample of 15-year-olds, linear and
      unmoderated relationships were found. Irrespective of their pubertal status,
      gender, or level of sexual experience, television viewing is related to higher
      expectations of peers' sexual activities. CONCLUSION: Concerns about the impact
      of television viewing on sexual health should not be limited to older
      adolescents. This research has identified 12-year-olds who display a higher level
      of pubertal development and generally spend much time with television viewing as
      a category of viewers-at-risk.

PMID- 15948884
TI  - Three-year follow-up of a family support service cohort of children with
      behavioural problems and their parents.
AB  - Abstract Background The aim of this study was to establish the medium-term (three
      year) psychosocial outcome of children with behavioural problems and their
      parents, who had received an intervention from a family support service. Methods
      Forty families were traced at the three-year follow-up and agreed to participate.
      Pre- and post-intervention and follow-up measures were the Health of the Nation
      Outcome Scales for Children and Adolescents (HoNOSCA) and the Strengths and
      Difficulties Questionnaire (SDQ). Results The primary HoNOSCA outcome items (i.e.
      those initially targeted by the parenting intervention) of aggression/antisocial
      behaviour and family relationships were not found to have changed significantly
      from the baseline (but had not sustained the sort-term improvement following the
      intervention). Deterioration was found in other HoNOSCA items such as
      overactivity, self-harm, scholastic/language skills, emotional, and poor school
      attendance. When we compared pre-intervention with follow-up SDQ scores, there
      was no significant change on any scales, i.e. these had returned to the level
      reported at the time of the original referral to the family support service.
      Conclusions Following the intervention from a family support service, children
      and families reported a significant improvement in most outcome measures,
      predominantly child behaviour and family relationships. However, these
      improvements were either not sustained or there were additional difficulties at
      three-year follow-up. These could be related to various external and
      developmental factors. This lack of sustainable treatment effects for children
      with behavioural problems is consistent with previous research findings on
      parenting programmes.

PMID- 15948885
TI  - Developmental differences in understanding the causes, controllability and
      chronicity of disabilities.
AB  - OBJECTIVE: The present study explored typically developing children's (n = 77)
      understanding of the causes, controllability and chronicity of disabilities.
      DESIGN: Children in each of four age groups (4-5 years, 6-7 years, 9-10 years and
      11-12 years) were interviewed to explore their ideas about children with physical
      disabilities (minor: missing thumb; major: wheel-chair bound), sensory
      disabilities (blindness and hearing loss), learning disabilities (non-specific
      and Down syndrome) and emotional/behavioural difficulties (attention deficit
      hyperactivity disorder and lack of social skills). RESULTS: Significant age
      differences were found in children's understandings of the causes,
      controllability and chronicity of disabilities. Furthermore, children showed a
      greater understanding of salient disabilities. CONCLUSIONS: Findings are
      discussed in terms of developmental changes and the role of experience in shaping
      children's understanding of disabilities.

PMID- 15948894
TI  - Amino acid-dependent modulation of glucose metabolism in humans.
AB  - Despite its high prevalence and severe complications, the aetiology of the
      primary defects leading to Type 2 diabetes mellitus remain unknown. In addition
      to polygenic predisposition, environmental factors including dietary behaviour
      are increasingly recognized as being of crucial importance for the development of
      this disease. This strongly supports the concept that nutrient excess leading to
      increased availability of substrates adversely influences whole-body metabolic
      regulation and plays a major role in the development of type 2 diabetes. We have
      shown previously that a short-term increase in free fatty acid availability
      impairs glucose metabolism in liver and skeletal muscle. Despite the widespread
      interest in protein-rich diets, the effects of plasma amino acid elevation on
      human glucose metabolism have not yet been studied in detail. This editorial
      summarizes recent advances in the identification of mechanisms responsible for
      amino acid-dependent modulation of glucose metabolism in liver and skeletal
      muscle in vivo.

PMID- 15948895
TI  - Left atrial systolic reserve in idiopathic vs. ischaemic-dilated cardiomyopathy.
AB  - PURPOSE: There are studies indicating more pronounced left atrial (LA) systolic
      dysfunction at rest in idiopathic (IDDC) than in ischaemic-dilated cardiomyopathy
      (ISDC). It was hypothesized that the findings would be similar with regards LA
      systolic reserve. METHODS: Twenty-six patients with IDDC, 28 with ISDC and 25
      normal controls underwent low-dose dobutamine stress echocardiography (5-10
      microg kg(-1) min(-1) IV). Left atrial volumes were echocardiographically
      determined at rest and during stress at the mitral valve opening (maximal, Vmax),
      electrocardiographic P wave (onset of atrial systole, Vp) and mitral valve
      closure (minimal, Vmin) from the apical 4- and 2-chamber views (biplane area
      length method). Left atrial systolic function was assessed with the LA-active
      emptying volume (ACTEV) = Vp-Vmin and fraction (ACTEF) = ACTEV/Vp. RESULTS: Vmax
      at rest was similar in IDDC and ISDC and greater than in the controls (54.2 +/-
      12 vs. 48.5 +/- 18 vs. 27.1 +/- 6.3 cm(3) m(-2), respectively, P < 0.001) and did
      not change with stress (53.9 +/- 13.8 vs. 46.9 +/- 16.2 vs. 25.8 +/- 5.9 cm(3) m(
      2), P < 0.001). The ACTEV at rest was similar in IDDC and ISDC and greater than
      in the controls (8.6 +/- 3.5 vs. 9.7 +/- 2.9 vs. 6.1 +/- 2.2 cm(3) m(-2) P <
      0.01), whereas during the dobutamine infusion it remained unaltered in IDDC (10.8
      +/- 4.6 cm(3) m(-2), P = NS vs. rest) and increased in ISDC (11.8 +/- 3.3 cm(3)
      m(-2), P < 0.05) and the controls (13.1 +/- 3.2 cm(3) m(-2), P < 0.01). The ACTEF
      was lower in IDDC than ISDC and the controls at rest (20 +/- 10% vs. 33 +/- 8%
      vs. 36 +/- 10%, P < 0.01). Dobutamine infusion was associated with no significant
      increase in ACTEF in IDDC (25 +/- 12%, P = NS vs. rest), and with an increase in
      this variable in ISDC (39 +/- 10%, P < 0.05) and the controls (49 +/- 12%, P <
      0.01). CONCLUSIONS: Dobutamine infusion is associated with an increase in LA
      ACTEV and fraction in ISDC and no significant change in these indices in IDDC.
      These findings indicate a reduced LA systolic reserve in IDDC.

PMID- 15948896
TI  - L-arginine fails to protect against myocardial remodelling in L-NAME-induced
      hypertension.
AB  - BACKGROUND: We investigated whether the substrate for nitric oxide synthesis L
      arginine is able to modify hypertension and left ventricular hypertrophy
      development induced by chronic blockade of nitric oxide synthase activity by NG
      nitro-L-arginine-methyl ester (L-NAME). MATERIAL AND METHODS: Four groups of rats
      were investigated: control, L-arginine 1.5 g kg-1, L-NAME 40 mg kg-1, and L-NAME
      +L-arginine in corresponding doses. Systolic blood pressure was measured by non
      invasive tail-cuff plethysmography each week. After 4 weeks, the animals were
      sacrificed and hydroxyproline and coenzyme Q9 and Q10 concentrations in the left
      ventricle, and nitric oxide synthase activity in the left ventricle, kidney and
      brain were investigated. RESULTS: In the L-NAME group, nitric oxide synthase
      activity was decreased in the left ventricle, kidney and brain, and hypertension,
      left ventricular hypertrophy and fibrosis developed. Heart remodelling was
      associated with the decrease of coenzyme Q9 and Q10 concentrations in the left
      ventricle. Simultaneous treatment with L-NAME and L-arginine prevented nitric
      oxide synthase activity diminution in the left ventricle but not in the kidney
      and brain, and completely failed to prevent hypertension, left ventricular
      hypertrophy and fibrosis. Nevertheless, l-arginine prevented the diminution of
      coenzyme Q9 and Q10 concentrations in the left ventricle. CONCLUSIONS: We
      conclude that L-arginine failed to prevent hypertension, left ventricular
      hypertrophy and fibrosis development despite restoration of nitric oxide synthase
      activity in the left ventricle. However, L-arginine prevented the diminution of
      coenzyme Q levels in the left ventricle.

PMID- 15948897
TI  - Liver alanine aminotransferase, insulin resistance and endothelial dysfunction in
      normotriglyceridaemic subjects with type 2 diabetes mellitus.
AB  - BACKGROUND: Plasma levels of liver transaminases, including alanine
      aminotransferase (ALT), are elevated in most cases of nonalcoholic fatty liver
      disease (NAFLD). Elevated ALT levels are associated with insulin resistance, and
      subjects with NAFLD have features of the metabolic syndrome that confer high-risk
      cardiovascular disease. Alanine aminotransferase predicts the development of type
      2 diabetes (DM2) in subjects with the metabolic syndrome. However, the role of
      elevated ALT levels in subjects with overt DM2 has yet not been explored.
      MATERIALS AND METHODS: In a cross-sectional study, 64 normotriglyceridaemic
      subjects with DM2 were studied with regard to the relation between liver
      transaminases with whole-body insulin sensitivity, measured with the euglycaemic
      hyperinsulinaemic clamp and with brachial artery flow-mediated dilation (FMD) as
      a marker of endothelial dysfunction. RESULTS: On average, patients were
      normotriglyceridaemic (plasma triglycerides 1.3 +/- 0.4 mmol L-1) and had good
      glycaemic control (HbA1c 6.2 +/- 0.8%). The mean ALT level was 15.0 +/- 7.5 U L
      1, and the mean aspartate aminotransferase concentration equalled 10.6 +/- 2.6 U
      L-1. Alanine aminotransferase levels were negatively associated with whole-body
      insulin sensitivity as well as with FMD (both P = 0.03, in multivariate analyses;
      regression coefficients beta [95%CI]: -0.76 [-1.4 to -0.08] and -0.31 [-0.58 to 
      0.03] respectively). CONCLUSIONS: In metabolically well-controlled patients with
      DM2, ALT levels are related to decreased insulin-sensitivity and an impaired
      conduit vessel vascular function.

PMID- 15948898
TI  - Treatment of osteoporotic ovariectomized rats with 24,25(OH)2D3.
AB  - BACKGROUND: Antiresorptive therapeutic regimens are the mainstay of current
      management of osteoporosis. Treatments that are promoting new bone formation are
      less available and less affordable. Previous studies have suggested that
      24,25(OH)(2)D(3) could enhance bone formation. The effect of 24,25(OH)(2)D(3) on
      bone formation in ovariectomized osteopenic rats (OVX) was evaluated in this
      study. MATERIALS AND METHODS: Mature Sabra rats were divided into two groups:
      sham-operated and OVX. Three months after surgery the OVX and sham-operated rats
      were divided into the following subgroups: (1) sham rats injected with vehicle,
      (2) sham rats injected with 24,25(OH)(2)D(3), (3) OVX rats injected with vehicle,
      and (4) OVX rats injected with 24,25(OH)(2)D(3). After 2 weeks' treatment,
      histomorphometry of the right tibiae was performed. RESULTS: Ovariectomy resulted
      in a decrease in total bone volume (TBV/TV) and in bone formation (BFR/BS), P <
      0.005 and P < 0.05 respectively, when compared with the sham-operated rats.
      Beside the decrease in TBV and BFR, the OVX rats showed an increase in
      osteoclastic bone resorption (P < 0.001 vs. sham). Administration of
      24,25(OH)(2)D(3) was followed by an increase in all static and dynamic bone
      forming parameters. The TBV/BV (P < 0.025), osteoblast surface (Ob.S/BS) (P <
      0.001), as well as the BFR/BS (P < 0.005), increased in the OVX-treated group
      when compared with the OVX-untreated and sham-operated rats. This increment in
      bone formation was associated with a decrease in bone resorption (P < 0.001 in
      OVX-treated vs. OVX-untreated rats). CONCLUSIONS: This study shows that
      24,25(OH)(2)D(3) may be of benefit in experimental osteopenia following
      ovariectomy, both by suppressing osteoclastic hyperactivity and by stimulating
      bone formation.

PMID- 15948899
TI  - Age-related thymic activity in adults following chemotherapy-induced lymphopenia.
AB  - BACKGROUND: The potential role of the adult thymus in T-cell homeostasis
      subsequent to lymphopenia remains the subject of debate. We examined whether
      thymic activity contributes to reconstitution of the peripheral T-cell pool, a
      critical process for patients recovering from antineoplastic therapy. METHODS: In
      selected patients with various neoplastic diseases we assessed peripheral blood
      lymphocyte subsets by flow-cytometry, including thymus-derived, CD4+ T cells
      expressing the CD45RA molecule, and thymic size rebound by CT scan before, and 3,
      6 and 12 months after completion of cytotoxic therapy. RESULTS: Adult patients (n
      = 21, mean age of 30 years, range 18-49) had higher baseline numbers of B and
      lower numbers of NK cells than elderly patients (n = 15, mean age of 79 years,
      range 70-91), while total T-cell numbers did not differ. Despite the reduction of
      lymphocyte counts being comparable in the adult (mean of 45%) and elderly (mean
      of 49%) groups, occurring at, or near, completion of treatment, an enlargement of
      the previously atrophic thymus was evident in 63% of the adult, but in none of
      the elderly, subjects. In 22 patients who remained active disease-free during the
      following year, B cells and NK cells recovered to pretreatment levels as soon as
      at 3 months, whereas overall T-cell recovery occurred at 6 months post-treatment.
      Thymic rebound, observed in 11 of 22 patients who were of younger age, correlated
      significantly with a faster and more complete recovery of CD45RA+ CD4+ (mainly
      helper-naive) T cells. CONCLUSION: The adult thymus appears capable of
      regeneration, at least up to middle age, contributing significantly to the
      reconstitution of the peripheral T-cell pool following chemotherapy-induced
      lymphopenia. In advanced age, however, although peripheral homeostatic pathways
      appear intact, regeneration of the naive repertoire is incomplete.

PMID- 15948900
TI  - Five cardiac hormones decrease the number of human small-cell lung cancer cells.
AB  - BACKGROUND: Four peptide hormones of a family of six hormones, i.e. atrial
      natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-natriuretic peptide
      (CNP), long acting natriuretic peptide (LANP), vessel dilator and kaliuretic
      peptide, significantly decrease the number of adenocarcinoma cells in culture.
      The present investigation was designed to determine whether these peptide
      hormones' effects are specific to adenocarcinomas or whether they might decrease
      the number of cancer cells of a different type of cancer, i.e. small-cell lung
      cancer. METHODS AND MATERIALS: These six hormones were evaluated for their
      ability to decrease the number and/or proliferation of human small-cell lung
      cancer cells in culture for 24, 48, 72, and 96 h. RESULTS: Within 24 h, vessel
      dilator, LANP, kaliuretic peptide, ANP and their intracellular mediator cyclic
      GMP, each at 1 microM, decreased the number of small-cell lung cancer cells by
      63% (P < 0.001), 21% (P < 0.05), 30% (P < 0.05), 39% (P < 0.05), and 31% (P <
      0.05), respectively. There was no proliferation in the 3 days following this
      decrease in cell number. These same hormones decreased DNA synthesis 68% to 82%
      (P < 0.001). Brain natriuretic peptide and CNP did not decrease the number of
      small-cell lung cancer cells or inhibit their DNA synthesis at 1 microM or 10
      microM concentrations. Dose-response curves revealed that at 100 microM, the
      vessel dilator decreased 92% of the cancer cells in 24 h while BNP had no effect,
      but CNP caused a 39% decrease. Western blots revealed that the natriuretic
      peptide receptors A- and C- were present in these cancer cells. CONCLUSIONS: Five
      peptide hormones significantly decrease the number of human small-cell lung
      cancer cells within 24 h and inhibit their proliferation for at least 96 h. Their
      mechanism of doing so involves inhibition of DNA synthesis mediated in part by
      cyclic GMP.

PMID- 15948901
TI  - Heightened levels of circulating 20S proteasome in critically ill patients.
AB  - BACKGROUND: Recently, circulating proteasome core particles (20S proteasome) have
      been suggested as a marker of cell damage and immunological activity in
      autoimmune diseases. Aberrant leucocyte activation and increased lymphocyte
      apoptosis with consecutive T-cell unresponsiveness is deemed to play a pivotal
      role in the sepsis syndrome. Moreover sepsis-induced muscle proteolysis mainly
      reflects ubiqutin proteasome-dependent protein degradation. We therefore sought
      to investigate serum levels of 20S proteasome in critical ill patients. MATERIAL
      AND METHODS: Case-control-study at a university hospital intensive care unit; 15
      patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients
      recruited within 24 h of admission to the ICU, a control group of 15 patients who
      underwent abdominal surgery, and 15 healthy volunteers. ELISA was used to measure
      the concentration of 20S proteasome in the sera of the patients and controls.
      Data are given as mean +/- SEM. Mann-Whitney U-test was used to calculate
      significance and a P-value of 0.05 was considered to be statistically
      significant. RESULTS: Marked increase of 20S proteasome was detected in the sera
      of septic patients (33 551 +/- 10 034 ng mL-1) as well as in trauma patients (29
      669 +/- 5750 ng mL-1). In contrast, significantly lower concentrations were found
      in the abdominal surgery group (4661 +/- 1767 ng mL-1) and in the healthy control
      population (2157 +/- 273 ng mL-1). CONCLUSION: Detection of 20S proteasome may
      represent a novel marker of immunological activity and muscle degradation in
      sepsis and trauma patients, and may be useful in monitoring the clinical effect
      of proteasome-inhibitors.

PMID- 15948902
TI  - Early and late failure of noninvasive ventilation in chronic obstructive
      pulmonary disease with acute exacerbation.
AB  - BACKGROUND: Despite recent encouraging results, the use of noninvasive
      ventilation (NIV) in the management of acute exacerbations in chronic obstructive
      pulmonary disease (COPD), complicated by acute respiratory failure (ARF), is not
      always successful. Failure of NIV may require an immediate intubation after a few
      hours (usually 1-3) of ventilation ('early failure') or may result in clinical
      deterioration (one or more days later) after an initial improvement of blood gas
      tension and general conditions ('late failure'). MATERIALS AND METHODS: We
      enrolled 122 patients affected by COPD complicated by ARF, and treated with NIV.
      The schedule of NIV provided sessions of 2-6 h twice daily. RESULTS: Ninety-nine
      (81%) patients showed a progressive improvement of the clinical parameters and
      were discharged. Among the remaining 23 patients, 13 had an early failure and 10
      had a late failure. In the 'success' group and 'late failure' groups we found
      after an increase of pH 2 h of NIV (from 7.31 +/- 0.05 to 7.38 +/- 0.04 P < 0.001
      and from 7.29 +/- 0.03 to 7.36 +/- 0.02 P < 0.001, respectively) and a decrease
      of PaCO2 (from 80.93 +/- 9.79 to 66.48 +/- 5.95 P < 0.001 and from 85.96 +/-
      10.77 to 76.41 +/- 11.02 P < 0.001, respectively). After 2 h of NIV in the 'late
      failure' group there were no significant changes in terms of pH (from 7.20 +/-
      0.10 to 7.28 +/- 0.06) nor PaCO2 (from 92.86 +/- 35.49 to 93.68 +/- 23.68). The
      'early failure' group had different characteristics and, owing to more severe
      conditions, the value of pH, of Glasgow Coma Score, and Apache II Score were the
      best predictors of the failure; while, among the complications on admission,
      metabolic alterations were the only independently significant predictor.
      CONCLUSIONS: Our study confirms that NIV may be useful to avoid intubation in
      approximately 80% of patients with COPD complicated by moderate-severe
      hypercapnic respiratory failure.

PMID- 15948903
TI  - WNK4 regulates airway Na+ transport: study of familial hyperkalaemia and
      hypertension.
AB  - BACKGROUND: WNK [With No K (lysine)] kinases are essential for regulation of
      blood pressure and potassium homeostasis. WNK4 expression was recently found not
      only in the distal nephron but also in chloride-transporting epithelia. To
      establish a physiological role for this distribution we studied patients with
      familial hyperkalaemia and hypertension (FHH), [pseudohypoaldosteronism type II
      (PHAII)], which is caused by mutations in WNK4. DESIGN: Measurement of nasal
      potential difference (NPD) and sweat electrolytes were performed in controls, in
      six subjects with FHH and ten subjects with cystic fibrosis (CF). RESULTS: Basal
      NPD was higher in FHH compared with controls (n = 20): 22.8 +/- 5.7 vs. 16.2 +/-
      5.3 mV, respectively (P = 0.014). Maximal response to amiloride was also higher
      in FHH compared with controls: 14.8 +/- 3.5 vs. 10.0 +/- 4.8 mV, respectively (P
      = 0.03). In CF these values were 42.9 +/- 9.3 and 29.9 +/- 7.4 mV, respectively.
      The kinetics of the amiloride effect were faster in FHH, and as first reported
      here also in CF, compared with controls. At 30 s, amiloride-inhibitable residual
      PD in FHH was 50 +/- 30 vs. 81 +/- 9% in controls (P = 0.0003) and 56 +/- 7% in
      CF. The response to chloride-free and isoproterenol solutions, which determines
      chloride transport activity, was similar in FHH compared with controls [16.0 +/-
      8.6 vs. 10.4 +/- 5.9 mV (P = 0.08)]. Sweat conductivity in FHH was 49.7 +/- 7.3
      vs. 38.2 +/- 8.1 mmol (NaCl eq) L-1 in 16 controls (P = 0.007) and 94.0 +/- 19.3
      in CF. CONCLUSIONS: Mutant WNK4 increases Na+ transport in airways, and therefore
      it is regulated by wild-type WNK4. This may be caused by a regulation of ENaC or
      a K+ channel.

PMID- 15948904
TI  - The National Health Performance Framework: an evaluation model for use by
      psychiatrists.
AB  - OBJECTIVES: To demonstrate the use of the National Health Performance Framework
      as an evaluation framework for clinical interventions and service outcomes in
      mental health. CONCLUSIONS: Evaluation is not a complex process. What is required
      is a willingness to be accountable for outcomes of care. It does not require
      complex data systems but openness to scrutiny through reflective practices and a
      commitment to continue to explore the possibilities of making things better.

PMID- 15948905
TI  - Strategic planning and public mental health services.
AB  - OBJECTIVES: To provide an overview of approaches to strategic planning and to
      examine issues in relation to their applicability to public mental health
      services. CONCLUSIONS: Strategic planning is important for optimal functioning of
      mental health services in an increasingly complex environment. Although each
      approach will have advantages depending on context, the overall principles of the
      learning organization developed by Senge have particular relevance for mental
      health services.

PMID- 15948906
TI  - Organizational change management in mental health.
AB  - OBJECTIVE: To discuss change management as applicable to mental health.
      CONCLUSIONS: As mental health care grows increasingly complex, and the network of
      accountability widens, change is both inevitable and necessary. Strategies to
      introduce change effectively are essential. Resistance by medical staff to change
      often has a sound basis and must be acknowledged and explored. Change in clinical
      systems and practice is facilitated by careful planning and preparation, and by
      engaging clinicians in all phases of the change process; change will fail if this
      is not achieved. A number of management models facilitate the understanding and
      process of change.

PMID- 15948907
TI  - A survey of alcohol and drug services to general hospitals in Australia.
AB  - OBJECTIVE: To determine the structure and function of alcohol and drug services
      to general hospitals in Australia, and to examine the role psychiatry plays in
      those services. METHOD: A survey of 15 large metropolitan hospitals was
      conducted. RESULTS: Services differed considerably between hospitals, and
      psychiatric involvement was not prominent in most. CONCLUSIONS: One of the
      challenges is to structure the administration of services so that they have a
      profile within the general hospital as well as close connection with community
      services. Psychiatrists must become more proactive in the area to reinforce what
      they have to offer these patients and to provide mentorship and training to
      psychiatric trainees in the field.

PMID- 15948908
TI  - Assertive community treatment of the mentally ill: service model and
      effectiveness.
AB  - OBJECTIVE: To provide a description of the service delivery model of an assertive
      community treatment (ACT) team in the management of a group of severely mentally
      ill patients and examine the effectiveness of this team in reducing readmissions
      to a psychiatric inpatient service. METHOD: A clinical case audit was performed
      on a single day in September 2001. Admission episodes and duration were collected
      for patients registered with the team in the 12 month period prior to ACT and for
      a period of 12 months ending on the day of the audit. Forty-three patients were
      registered with the team at the time of data collection. The majority (79%) were
      diagnosed with schizophrenia and there were high rates of comorbidity (76%) and
      disability (mean Global Assessment of Functioning score 45.9). The main outcome
      measures were the number of readmissions and readmission days before and after
      the institution of ACT. RESULTS: The mean number of readmission days reduced from
      70.9 to 10.2 (p<0.05) following the institution of ACT. CONCLUSION: Assertive
      community treatment conducted in a naturalistic clinical environment is effective
      in significantly reducing the number of readmission days in a group of patients
      suffering from long-term and persistent severe mental illness.

PMID- 15948910
TI  - Building an ECT service: an outcomes-equivalent approach.
AB  - OBJECTIVE: Specific guidelines, ongoing controversies in technique and audit
      reviews have made clinicians wary about continuing in electroconvulsive therapy
      (ECT). This paper attempts to reassure practitioners by incorporating such
      changes into a simple approach to ECT based on outcomes equivalence. METHOD: A
      selected compilation of the recent literature was used to describe a model for
      starting and/or continuing an effective ECT service. RESULTS: It was suggested
      that a useful way of approaching ECT service delivery is to focus on what is
      actually important, getting patients better, and to do so within the context and
      capability of each hospital. CONCLUSIONS: ECT is a changing field. Remaining true
      to the core principles of clinical practice, patient selection and technique,
      provides a basis for beginning, continuing and further developing an effective
      ECT service.

PMID- 15948909
TI  - Impact of a crisis assessment and treatment service on admissions into an acute
      psychiatric unit.
AB  - OBJECTIVE: To assess the impact of a regional/rural crisis assessment and
      treatment service (CAT) on admissions into an acute adult inpatient psychiatric
      facility. METHODS: Relevant data for admissions into an acute adult inpatient
      psychiatric facility in the 18 month periods before and after the establishment
      of a CAT were compared. Data extracted from available clinical records were
      transferred into an appropriately structured pro forma for statistical analysis.
      RESULTS: There were 69 and 53 index inpatient unit admissions in the two time
      periods. The majority of these were for single, unemployed men aged in their 30s.
      Although statistically non-significant, the results appear to suggest that there
      were proportionately fewer readmissions and that admissions were likely to be
      influenced by illness severity and diagnostic considerations in the period
      following the establishment of the CAT. The establishment of CAT did not appear
      to have had much impact on the duration of psychiatric hospitalization.
      CONCLUSIONS: Crisis assessment and treatment services operating within a
      regional/rural integrated mental health setting appear to have only limited
      impact on hospitalization for psychiatric crisis presentations. There is a need
      for further studies looking at a broader range of outcome variables in the
      assessment of the impact of CAT on psychiatric hospitalization in such settings.

PMID- 15948911
TI  - Helping carers care: an education programme for rural carers of people with a
      mental illness.
AB  - OBJECTIVE: To provide descriptive information about a short-term educational
      programme for rural carers of people with a mental illness, living in the Loddon
      Campaspe Southern Mallee region. METHOD: The Carers Education Exchange Programme
      is a flexible, needs-based model that can be modified to cater for individual
      groups. It consists of a number of sessions on topics relevant to caring for
      someone with a mental illness, held over a period of several weeks. The programme
      is offered at locations throughout the region, making it accessible to carers in
      isolated, rural areas. RESULTS: Feedback indicates that the benefits of
      participating in the programme include the reduction of isolation and stigma,
      increased understanding of mental illness, development of skills relevant to the
      caring role and the formation of supportive networks, both professional and
      personal. CONCLUSIONS: Educational group programmes for carers are an effective
      way of providing both education and support. This programme can assist in
      reducing some of the distress and difficulties inherent in caring for someone
      with a mental illness. Carer well-being is enhanced by the promotion of self-care
      and a positive outlook.

PMID- 15948912
TI  - Beyond the chalkboard: the interacting domains in undergraduate psychiatric
      teaching.
AB  - OBJECTIVE: To identify and describe interacting domains that are present during
      undergraduate psychiatric teaching and impress on educators the roles of these
      domains. CONCLUSIONS: Undergraduate psychiatric teaching is an essential part of
      general family physicians' training and practice. Undergraduate students'
      exposure to psychiatry might be inadequate. Curricular goals, teaching and
      evaluation of students need to be aligned. Research and information technology
      can play a bigger role in teaching. Validation of patients, students and teachers
      during the teaching process is important, but not always emphasized. Educators
      should be aware of society's unwritten expectations, judgements and opinions of
      mental illness sufferers. Identifying and facilitating the various interacting
      domains during psychiatric teaching may contribute to better education in
      psychiatry, better retention of knowledge for students and an improved
      recruitment of students to a psychiatric career.

PMID- 15948913
TI  - The beyondblue Schools Research Initiative: conceptual framework and
      intervention.
AB  - OBJECTIVE: To describe the rationale, conceptual framework and content of the
      intervention for the beyondblue Schools Research Initiative. CONCLUSIONS: The
      beyondblue Schools Research Initiative aims to prevent the development of
      depression in young people through increasing individual and environmental
      protective factors within the school context. The model draws on evidence that
      demonstrates the important role played by individual and environmental
      characteristics in buffering the impact of adversity. The school provides a forum
      in which both individual and environmental change may be produced in order to
      increase some of these key protective characteristics. The project also draws
      together health, education and other key services to provide more effective
      pathways to enable young people to receive professional help when required.

PMID- 15948914
TI  - Hospital admission in adolescents with acute psychiatric disorder: how long
      should it be?
AB  - OBJECTIVE: To determine the length of stay in hospital for youth with acute
      psychiatric illness, and the treatment outcome. METHODS: Diagnostic and
      Statistical Manual of Mental Disorders (4th edn; DSM-IV) psychiatric diagnosis,
      clinical outcome and the length of stay were systematically gathered for
      admissions over an 18 month period at the Christchurch Youth Inpatient Unit
      (YIU). Clinical outcome data were collected at admission, 3 weeks after admission
      and at discharge, using the Health of the Nation Outcome Scale for Children and
      Adolescents (HoNOSCA). The length of stay was determined retrospectively.
      Discharge was decided on clinical grounds. RESULTS: During the 18 months of the
      investigation, 72 subjects were admitted for the treatment of acute mental
      illness. The most common diagnostic category was mood disorder (n=39, 54%),
      followed by anxiety or adjustment disorder (n=18, 25%), and major psychosis
      (n=15, 21%). The mean length of admission for the whole population was 27.3 days,
      23.7 days for mood disorders, 18.9 days for anxiety disorders and 46.9 days for
      the major psychosis diagnostic groups. According to HoNOSCA clinician ratings,
      the major portion of the improvement occurred during the first 3 weeks of
      admission. CONCLUSIONS: For the majority of youth with acute psychiatric illness,
      a relatively short stay in hospital is feasible, because most health gains tend
      to occur early during an admission.

PMID- 15948915
TI  - Redevelopment of a consultation-liaison service at a tertiary paediatric
      hospital.
AB  - OBJECTIVE: This paper aims to describe the way a multidisciplinary team set out
      to redevelop a consultation-liaison (C-L) service at a tertiary paediatric
      hospital. METHOD: The activities and processes in which the team members engaged
      were documented within a continuous quality improvement cycle. These activities
      included literature review, analysis of referral patterns, consultation with
      extant services, survey of referral sources and consultation with other tertiary
      paediatric services. RESULTS: The outcomes of these initiatives were integrated
      into a re-formulated multidisciplinary team model dedicated to providing C-L
      services to the paediatric hospital. Significant challenges identified in the
      initial process were ongoing issues with caseload management and clarification of
      boundary demarcations. CONCLUSION: There has been a gradual acceptance of the new
      C-L service by medical staff. The structure has resulted in a focused and
      coordinated C-L team that has contributed to innovations in the C-L process
      within the hospital.

PMID- 15948916
TI  - Lessons learnt in conducting a clinical drug trial in children with Asperger
      Syndrome.
AB  - OBJECTIVE: To describe the authors' experience of conducting a clinical drug
      trial in children with Asperger Syndrome, including the pitfalls encountered and
      lessons learnt. CONCLUSIONS: The main barrier encountered was in the recruitment
      of children: it was not possible to recruit the target of 60 patients. The
      recruitment of children is often the major barrier to the progress of a
      successful clinical trial. Conducting the clinical drug trial was greatly
      facilitated by the appropriate setting and experienced clinical pharmacology
      staff.

PMID- 15948917
TI  - General practitioners and mental health staff sharing patient care: working
      model.
AB  - OBJECTIVE: The paper describes a shared care programme developed by mental health
      services and general practitioners for shifting patients with chronic psychiatric
      disorders to the care of a general practitioner. The programme is characterized
      by: (i) a dedicated mental health service general practitioner liaison position
      to manage the programme and provide support to both patients and doctors; (ii) a
      multidisciplinary care planning meeting that includes mental health staff, the
      patient, the general practitioner and a carer; and (iii) a jointly developed
      individual management plan that specifies patient issues, strategies to deal with
      these issues, persons responsible for monitoring and a review date. METHODS: The
      shared care protocol, the results of a review of patient mental health indicators
      and general practitioner satisfaction with the programme are described. RESULTS:
      Outcomes to date suggest that patients' mental health is not compromised and may
      be enhanced by transfer to general practitioners within the shared care model.
      Indicators of mental health outcomes (Health of the Nation Outcome Scale and Life
      Skills Profile scores) show improved patient symptomatology and functioning in
      most cases. CONCLUSIONS: The programme fits the model of recovery-based mental
      health services and complies with current local, state and Commonwealth policies
      that encourage integrated and collaborative approaches by mental health services
      and general practitioners in delivering mental health care to persons with
      chronic mental illness.

PMID- 15948918
TI  - Mental health research in general practice.
AB  - OBJECTIVE: To explore problems in carrying out a mental health research project
      in the general practice setting. METHOD: Open-ended interviews were conducted
      with general practice stakeholders, focusing on impediments to the conduct of
      mental health research in general practice and possible means for improving the
      participation of general practitioners in such research. Participants in the
      consultations were members of five divisions of general practice, senior staff
      within an academic department of general practice, four general practitioners and
      a research group engaged with general practice research. The discussions were
      recorded in detailed interview notes, and key issues and themes emerging from
      consultations were derived by the researchers. RESULTS: Three main themes
      summarized most of the issues reported through the consultations, including
      structural issues (e.g. disruption of practice, time limitations and lack of
      remuneration), process issues (e.g. researcher-general practice communication,
      researcher-imposed issues and need for partnerships) and content issues (e.g.
      study design, study procedures and methods). CONCLUSIONS: The consultations
      revealed similar findings to previously published reports concerning general
      practice research, with an emphasis on the need for partnerships between
      researchers and general practice organizations in the conduct of such research.

PMID- 15948919
TI  - A model of supervision in mental health for general practitioners.
AB  - OBJECTIVE: If general practitioners (GPs) are to provide effective ongoing care
      to patients with mental health difficulties, it is argued that they need access
      to effective supervision. This paper aims to describe a specific framework for
      the provision of supervision to GPs involved in mental health-related work in a
      rural area. CONCLUSIONS: An innovative model of supervision is currently being
      trialled with GP practices in the Bendigo area of country Victoria. It is
      essential for a formal supervision framework to be available for GPs in mental
      health, so that effective outcomes in primary mental health care are maximized,
      facilitating better support for GPs and better outcomes for patients with mental
      health difficulties.

PMID- 15948920
TI  - Mental health policy development: case study of Cambodia.
AB  - OBJECTIVE: To identify key issues in the mental health policy development process
      in Cambodia that will contribute to an increased understanding of how mental
      health policy gets on the public policy agenda, how it stays there and why policy
      implementation fails or succeeds. The research was formative because mental
      health policy analysis is a young and newly emerging discipline. METHOD: A
      retrospective case study methodology was used to research the development of the
      draft Cambodian Mental Health Plan 2003-2022. Ten key informants involved in the
      policy development process were interviewed using a semistructured questionnaire
      designed to collect qualitative data about the policy formation process,
      stakeholders and context. RESULTS: The research identified key issues influencing
      mental health policy development. These are the need to include the Ministry of
      Health (MoH) in the development of mental health plans; the significance of
      timing; the usefulness of mental health plans; the impact of the post-conflict
      context on policy development; and the evolution of stakeholder groups and their
      need to learn how to debate the merits of mental health reform. CONCLUSIONS: The
      findings are formative given methodology limitations. However, important insight
      is provided into the dynamics of the policy development processes that occurred
      in Cambodia. This allows the generation of important hypotheses for future mental
      health policy process research in both Cambodia and other post-conflict
      developing countries.

PMID- 15948921
TI  - The New South Wales Inebriates Act: going, going, gone?
AB  - OBJECTIVE: To describe how the use of psychiatric hospitals as institutions for
      inebriates came about in New South Wales. CONCLUSIONS: A so-called 'temporary'
      solution to a political problem in 1929 led to the psychiatric hospitals in New
      South Wales becoming repositories for inebriates for the next 75 years. This
      unsatisfactory situation may be about to change.

PMID- 15948922
TI  - Administrators: masters or servants?

PMID- 15948923
TI  - Administrators: masters or servants?

PMID- 15948926
TI  - Introduction to tripartite meeting report (convenors: Dr Nigel Baber and Prof.
      Ros Smyth): towards establishing optimal doses for drugs prescribed to children.

PMID- 15948927
TI  - Better medicines for children--where are we now, and where do we want to be?

PMID- 15948928
TI  - Tripartite meeting. Paediatric regulatory guidelines: do they help in optimizing
      dose selection for children?

PMID- 15948929
TI  - Modelling approaches to dose estimation in children.
AB  - Most of the drugs on the market are originally developed for adults and dosage
      selection is based on an optimal balance between clinical efficacy and safety.
      The aphorism 'children are not small adults' not only holds true for the
      selection of suitable drugs and dosages for use in children but also their
      susceptibility to adverse drug reactions. Since children may not be subject to
      dose escalation studies similar to those carried out in the adult population,
      some initial estimation of dose in paediatrics should be obtained via
      extrapolation approaches. However, following such an exercise, well-conducted PK
      PD or PK studies will still be needed to determine the most appropriate doses for
      neonates, infants, children and adolescents.

PMID- 15948930
TI  - How children's responses to drugs differ from adults.
AB  - Children are not small adults. However, the main thesis of this review will be
      that children's responses to drugs have much in common with the responses in
      adults and indeed in other mammals. Often, it is assumed that drug effects differ
      in children but in reality this perception often arises because the drugs have
      not been adequately studied in paediatric populations of different ages and with
      different diseases. There may also be difficulties in measuring small but
      significant effects because the outcome measures are more difficult to assess in
      children. In some cases, stage of development can alter the action of, and
      response to, a drug - a truly age-dependent difference in pharmacodynamics. This
      may be true of both the desired action and adverse events. Examples are given.
      Programming by drugs is also a phenomenon almost exclusive to early life, i.e.
      permanent effects result from a stimulus applied at a sensitive point in
      development ('critical window'), often in fetal or neonatal life. Again, examples
      are discussed. Different pathophysiology, different disease variants, different
      pharmacodynamics, different 'host' response and different adverse drug reactions
      can all explain why some drugs behave differently in children. However, we need
      to explore ways to avoid re-inventing the wheel by determining how data from
      adult animal and human models can help inform research and practice for children.

PMID- 15948931
TI  - Formulation of medicines for children.
AB  - The development of age-adapted dosage forms and taste-masking of bitter-tasting
      drugs administered orally for children, are formidable challenges for formulation
      scientists. Childhood is a period of maturation requiring knowledge of
      developmental pharmacology to establish dose but the ability of the child to
      manage different dosage forms and devices also changes. Paediatric formulations
      must allow accurate administration of the dose to children of widely varying age
      and weight. Whilst the oral route will be preferred for long term use and the
      intravenous route for the acutely ill, many of the dosage forms designed for
      adults, such as oro-dispersible tablets, buccal gels and transdermal patches,
      would also benefit children if they contained an appropriate paediatric dose. The
      age at which children can swallow conventional tablets is of great importance for
      their safety. Liquid medicines are usually recommended for infants and younger
      children so the ability to mask unpleasant taste with sweeteners and flavours is
      crucial. More sophisticated formulations such as granules and oro-dispersible
      tablets may be required but there will be limitations on choice and concentration
      of excipients. There are many gaps in our knowledge about paediatric formulations
      and many challenges for the industry if suitable preparations are to be available
      for all ranges. A CHMP points to consider document is soon to be released. More
      research and clinical feedback are important because a formulation with poor
      acceptability may affect compliance, prescribing practice and ultimately
      commercial viability.

PMID- 15948932
TI  - Monitoring adverse drug reactions in children using community pharmacies: a pilot
      study.
AB  - AIMS: To determine the feasibility of a community pharmacy-based parental adverse
      drug reaction (ADR) reporting system for children. DESIGN: Prospective study of
      parent-reported ADRs using a questionnaire issued to the parent or guardians of
      children 0-11 years of age collecting prescribed medicine for amoxicillin, and/or
      salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or
      ibuprofen suspension. SETTING: Seven community pharmacies in Grampian, Scotland.
      RESULTS: During a 4-week period 360 prescriptions or purchases for the study
      medications occurred. Two hundred and sixty-seven parents (85.5%) agreed to
      participate in the study. One hundred and six participants (40%) returned a total
      of 122 questionnaires. The demographics of responders and nonresponders including
      medication, age of child, and social status as assessed by the Depcat score were
      similar. There was no evidence of under-representation of any socio-economic
      group. Possible adverse events were detected using a symptom tick list and
      perceived ADRs using free text entry. Using the symptom tick list approach the
      most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for
      amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen,
      paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%,
      respectively. Using the freehand section of the questionnaire 15 specific ADRs
      were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed
      to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity
      (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3),
      anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)],
      two to ibuprofen [diarrhoea (n = 1), not stated (n = )]. Only one off-label
      prescription was identified and this was for salbutamol syrup prescribed to a
      child under 2 years of age. CONCLUSIONS: The prospective monitoring of paediatric
      ADRs, using a questionnaire issued to parents or guardians in the community
      pharmacies, is feasible.

PMID- 15948933
TI  - Utility of routinely acquired primary care data for paediatric disease
      epidemiology and pharmacoepidemiology.
AB  - BACKGROUND: The majority of medicines prescribed for children are prescribed in
      primary care for common acute and chronic conditions. This is in contrast to
      prescribing in secondary care where the population of children admitted is small
      but where a large number of different medicines are prescribed to treat more
      serious and less common conditions. METHODS: Data on prescribing was extracted
      from the General Practice Administration System for Scotland (GPASS) for the year
      November 1999 to October 2000 and prescribing patterns for children aged 0-16
      years expressed as percentages. A comparison of age specific consultations for
      asthma, as an example of a common paediatric condition, was also made between two
      separate general practice data sets, the General Practice Research Database
      (GRPD) and the continuous morbidity recording (CMR) subset of GPASS. RESULTS: Of
      214 medicines investigated for unlicensed and off-label prescribing no unlicensed
      prescribing was identified. Off-label prescribing due to age was most common
      among younger and older children. The most common reasons for off-label
      prescriptions were, in order of frequency, lower than recommended dose, higher
      than recommended dose, below the recommended age, and unlicensed formulation. Age
      and gender specific consultations for asthma were similar in the two
      representative databases, GPRD and CMR, both showing disappearance of the male
      predominance in the teenage years. CONCLUSIONS: Large primary care data sets
      available within a unified health care system such as the UK National Health
      Service (NHS) are likely to be broadly compatible and produce similar results.
      The prescribing of off-label medicines to children is common in primary care,
      most commonly due to prescribing out with the recommended dosage regimen.

PMID- 15948934
TI  - Prediction of drug disposition in infants and children by means of
      physiologically based pharmacokinetic (PBPK) modelling: theophylline and
      midazolam as model drugs.
AB  - AIMS: To create a general physiologically based pharmacokinetic (PBPK) model for
      drug disposition in infants and children, covering the age range from birth to
      adulthood, and to evaluate it with theophylline and midazolam as model drugs.
      METHODS: Physiological data for neonates, 0.5-, 1-, 2-, 5-, 10- and 15-year-old
      children, and adults, of both sexes were compiled from the literature. The data
      comprised body weight and surface area, organ weights, vascular and interstitial
      spaces, extracellular body water, organ blood flows, cardiac output and
      glomerular filtration rate. Tissue: plasma partition coefficients were calculated
      from rat data and unbound fraction (f u) of the drug in human plasma, and age
      related changes in unbound intrinsic hepatic clearance were estimated from CYP1A2
      and CYP2E1 (theophylline) and CYP3A4 (midazolam) activities in vitro. Volume of
      distribution (V dss), total and renal clearance (CL and CL R) and elimination
      half-life (t(1/2)) were estimated by PBPK modelling, as functions of age, and
      compared with literature data. RESULTS: The predicted V dss of theophylline was
      0.4-0.6 l kg(-1) and showed only a modest change with age. The median prediction
      error (MPE) compared with literature data was 3.4%. Predicted total CL
      demonstrated the time-course generally reported in the literature. It was 20 ml
      h(-1) kg(-1) in the neonate, rising to 73 ml h(-1) kg(-1) at 5 years and then
      decreasing to 48 ml h(-1) kg(-1) in the adult. Overall, the MPE was - 4.0%.
      Predicted t(1/2) was 18 h in the neonate, dropping rapidly to 4.6-7.2 h from 6
      months onwards, and the MPE was 24%. The predictions for midazolam were also in
      good agreement with literature data. V dss ranged between 1.0 and 1.7 l kg(-1)
      and showed only modest change with age. CL was 124 ml h(-1) kg(-1) in the neonate
      and peaked at 664 ml h(-1) kg(-1) at 5 years before decreasing to 425 ml h(-1)
      kg(-1) in the adult. Predicted t(1/2) was 6.9 h in the neonate and attained
      'adult' values of 2.5-3.5 h from 1 year onwards. CONCLUSIONS: A general PBPK
      model for the prediction of drug disposition over the age range neonate to young
      adult is presented. A reference source of physiological data was compiled and
      validated as far as possible. Since studies of pharmacokinetics in children
      present obvious practical and ethical difficulties, one aim of the work was to
      utilize maximally already available data. Prediction of the disposition of
      theophylline and midazolam, two model drugs with dissimilar physicochemical and
      pharmacokinetic characteristics, yielded results that generally tallied with
      literature data. Future use of the model may demonstrate further its strengths
      and weaknesses.

PMID- 15948935
TI  - Allometric relationships between the pharmacokinetics of propofol in rats,
      children and adults.
AB  - AIMS: Allometric equations have proven useful for the extrapolation of animal
      data to determine pharmacokinetic parameters in man. It has been proposed that
      these equations are also applicable over the human size range including the
      paediatric population. The aim of this work was to study the relationship between
      various pharmacokinetic parameters for propofol and body weight using data from
      rats, children and adults. Furthermore, the utility of allometric scaling is
      evaluated by the prediction of propofol concentrations in humans based on data
      obtained in the rat. METHODS: The relationship between the pharmacokinetic
      parameters of propofol obtained in rats, children and adults was analyzed by
      plotting the logarithmically transformed parameters against the corresponding
      logarithmically transformed body weights. In addition, based on allometric
      equations, pharmacokinetic parameters obtained in rats were scaled to humans.
      These parameters were used to simulate propofol concentrations in long-term
      sedated critically ill patients using NONMEM. Simulated concentrations were then
      compared with actually observed concentrations in humans. RESULTS: The
      relationship between pharmacokinetic parameters of propofol from rats, children
      and adults was in good agreement with those from the literature on allometric
      modelling. For clearance, intercompartmental clearance, central volume of
      distribution and peripheral volume of distribution, the power parameters were
      0.78, 0.73, 0.98 and 1.1, respectively, and r2 values for the linear correlations
      were 0.990, 0.983, 0.977 and 0.994, respectively. On the basis of data obtained
      after a single bolus injection in the rat, adequate predictions of propofol
      concentrations in critically ill patients can be made using allometric equations,
      despite the long-term nature of the use of the drug, the large number of infusion
      changes per day and/or differences in state of health and age. CONCLUSIONS: For
      propofol, allometric scaling has proved to be valuable for cross species
      extrapolation. Furthermore, the use of the allometric equation between adults and
      children seems to be an adequate tool for the development of rational dosing
      schemes for children of varying body weights, and requires further study.

PMID- 15948936
TI  - Acute drug prescribing to children on chronic antiepilepsy therapy and the
      potential for adverse drug interactions in primary care.
AB  - AIMS: To investigate the extent of acute coprescribing in primary care to
      children on chronic antiepileptic therapy, which could give rise to potentially
      harmful drug-drug interactions. DESIGN: Acute coprescribing to children on
      chronic antiepileptic drug therapy in primary care was assessed in 178 324
      children aged 0-17 years for the year 1 November 1999 to 31 October 2000.
      Computerized prescribing data were retrieved from 161 representative general
      practices in Scotland. SETTING: One hundred and sixty-one general practices
      throughout Scotland. RESULTS: During the study year 723 (0.41%) children
      chronically prescribed antiepileptic therapy were identified. Fourteen
      antiepileptic agents were prescribed, with carbamazepine, sodium valproate and
      lamotrigine accounting for 80% of the total. During the year children on chronic
      antiepileptic therapy were prescribed 4895 acute coprescriptions for 269
      different medicines. The average number of acute coprescriptions for non
      epileptic drug therapy were eight, 11, six, and six for the 0-1, 2-4, 5-11, and
      12-17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%)
      prescribed to 22 (3.0%) children were identified as a potential source of
      clinically serious interactions. The age-adjusted prevalence rates for
      potentially serious coprescribing were 86, 26, 22, and 33/1000 children
      chronically prescribed antiepileptic therapy in the 0-1, 2-4, 5-11, and 12-17
      year-old age groups, respectively. The drugs most commonly coprescribed which
      could give rise to such interactions were antacids, erythromycin, ciprofloxacin,
      theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20
      children identified at risk of a potentially clinically serious adverse drug
      interaction, the acute coprescription was prescribed off label because of age or
      specific contraindication/warning. CONCLUSIONS: In primary care, 3.0% of children
      on chronic antiepileptic therapy are coprescribed therapeutic agents, which could
      give rise to clinically serious drug-drug interactions.

PMID- 15948937
TI  - Adverse drug reactions to nonsteroidal anti-inflammatory drugs, COX-2 inhibitors
      and paracetamol in a paediatric hospital.
AB  - AIMS: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in children has
      rapidly escalated over the last 5 years in Australia. This is primarily as a
      result of the availability of ibuprofen as an over-the-counter preparation.
      Several recent, significant adverse drug reactions (ADRs) to NSAIDs, at the Royal
      Children's Hospital (RCH) in Melbourne, Australia prompted review of all of the
      RCH reactions reported to these agents over 5 years. METHODS: The ADR programme
      documents both spontaneously reported ADRs and ADRs identified by discharge
      coding. For this study, reported reactions to aspirin, celecoxib, ibuprofen,
      indomethacin, naproxen, paracetamol and rofecoxib, for the previous 5-year
      period, were retrieved from the hospital ADR database. RESULTS: Nineteen reports
      of ADRs to NSAIDs and six to paracetamol, in patients aged from 4 months to 22
      years (median 10 years) were identified. Reactions were predominantly rash (n =
      10), gastrointestinal (n = 5) and respiratory (n = 4) side-effects. These
      included reports of haematemesis with both celecoxib and ibuprofen. One patient
      died of severe acute exacerbation of asthma following initiation of rofecoxib.
      CONCLUSION: NSAID exposures are a significant cause of morbidity in children.
      Both nonselective NSAIDs and the newer COX-2 inhibitors were associated with
      significant drug reactions. The overall severity of these ADRs highlights the
      need for vigilant surveillance of ADRs in paediatrics, including both established
      and newer agents.

PMID- 15948938
TI  - In vitro fertilization and childhood retinoblastoma.

PMID- 15948939
TI  - Should domperidone be used for the treatment of gastro-oesophageal reflux in
      children? Systematic review of randomized controlled trials in children aged 1
      month to 11 years old.
AB  - AIM: To determine whether there is robust evidence of efficacy for domperidone in
      reducing the symptoms of gastro-oesophageal reflux (GOR) and gastro-oesophageal
      reflux disease (GORD) in children. METHODS: Systematic review of randomized
      controlled trials (RCTs). A search was made of the Cochrane Library Issue 2004
      (Central Register of Controlled Trials and Database of Systematic Reviews),
      Medline (Pub-med) 1966 to present and Embase from 1974 to 2004, and reference
      citations of the RCTs that had been found electronically. RESULTS: Four RCTs were
      identified. Only the two older trials showed any benefits of domperidone on
      clinical symptoms of GORD in older children, which were the primary outcome
      measures. In the trial undertaken by Clara, a good or excellent result was
      obtained in 93% of the domperidone group compared with 33% of the controls (P <
      0.05). In the trial undertaken by de Loore, after 2 weeks of treatment 75% of
      patients treated with domperidone were found not to be vomiting, compared with
      43% in the metoclopramide group and 7% in the placebo group. The trial by
      Corraccio gave no detailed results regarding the primary outcomes of effect of
      domperidone on symptoms but simply reported 'cured', 'improved' or 'unchanged'.
      The secondary pH-metric outcome of the number of reflux episodes, was reduced
      with domperidone. CONCLUSION: From the limited evidence available, there was no
      robust evidence of efficacy for the treatment of GOR with domperidone in young
      children. Given the usually benign nature of the condition, the widespread use of
      unlicensed medicines for GOR is not warranted.

PMID- 15948940
TI  - Effect of the pediatric exclusivity provision on children's access to medicines.
AB  - AIMS: To determine the paediatric licensing status in the USA, UK, Australia and
      New Zealand of the 79 medicines granted paediatric exclusivity in the USA, and to
      assess the importance of those medicines to paediatric practice. METHODS: The
      medicines granted a patent extension in the USA as of 10 November 2003 were
      identified from the FDA website. Data on paediatric licensing were obtained from
      the Physicians Desk Reference (USA), the Electronic Medicines Compendium (UK),
      the Australian Prescription Products Guide (Australia) and the MedSafe website
      (New Zealand). A questionnaire was administered to seven paediatric consultants
      to assess the importance of the 79 PEMs for use in children. The questionnaire
      sought opinions on each drug, by age grouping, regarding: usefulness in patients
      with the condition, number of patients likely to be treated with each drug in a
      year, and acceptable therapeutic alternatives. RESULTS: Fifty-eight (73%) of the
      medicines had attained paediatric licensing in the USA. Sixty were licensed for
      adults in all four countries and of these 45 (75%) were licensed for children
      under 12 years in the USA compared with 31 (52%) to 33 (55%) for the other three
      countries. The proportion of these medicines licensed for children under 1 month,
      under 2 years and under 6 years of age ranged from 10% to 58% and there were no
      significant differences between the countries. For all four countries perceived
      usefulness and predicted numbers of patients both had some influence on the odds
      of a medicine having paediatric licensing. CONCLUSIONS: Improvements in licensing
      of some medicines for children have occurred in the USA, relative to the UK,
      Australia and New Zealand, subsequent to the Paediatric Exclusivity Provision.
      Improvements occurred for children over the age of six, but not for younger
      children.

PMID- 15948941
TI  - Changes in availability of paediatric medicines in Australia between 1998 and
      2002.
AB  - AIMS: To determine changes in the availability of medicines for children in
      Australia and to determine the status of newly introduced chemical entities by
      age category. METHODS: Using the Australian Prescription Products Guide and the
      Schedule of Pharmaceutical Benefits, licensed medicines available in Australia in
      the calendar years 1998 and 2002 were examined. RESULTS: The total number of
      medicines licensed in Australia increased from 1544 to 1903, the number of
      licensed paediatric items increased from 579 (37.5%) to 725 (38.1%), and those
      both licensed for paediatric use and subsidized increased from 356 (23.1%) to 441
      (23.2%). The number of medicines with formulations suitable for paediatric use
      increased from 861 (55.7%) to 967 (50.8%), and of these 382 (24.7%) and 466
      (24.5%) were licensed for paediatric use. Of the 90 new orally available chemical
      entities licensed for adults only 12 (13%) were licensed for children. Three (3%)
      were licensed for the 0-28 days and 28 days to 23 months age groups, eight (9%)
      for 2-11 years and 12 (13%) for 12-18 years. An additional 14 orally available
      chemical entities previously only licensed for adults, were licensed for children
      by 2002. CONCLUSIONS: There have been some improvements in medicines licensing
      for older children, but not for children under the age of two years.

PMID- 15948942
TI  - Paediatric homoeopathy in general practice: where, when and why?
AB  - AIMS: To investigate the extent of homoeopathic prescribing in primary care for
      childhood diseases and assess GP attitudes towards the use of homoeopathy in
      children. METHODS: Homoeopathic prescribing in primary care was assessed in 167
      865 children aged 0-16 years for the year 1999-2000. Computerized prescribing
      data were retrieved from 161 representative general practices in Scotland.
      Medical attitudes towards homoeopathic prescribing to children were also assessed
      via a questionnaire survey. RESULTS: During the year 1999-2000 22% (36) of
      general practices prescribed homoeopathic medicines to 190 (1.1/1000 registered)
      children. The majority of such prescriptions were issued to children under 1 year
      of age (8.0/1000 registered children). The most frequently prescribed medicines
      were for common self-limiting infantile conditions such as colic, cuts and
      bruises, and teething. A total of 259 completed questionnaires were returned by
      GPs, giving a response rate of 75%. GPs who frequently prescribed homoeopathic
      medicines to children (more than 1 per month) were more likely to claim an
      interest in homoeopathy, have had a formal training and keep up to date in the
      discipline, and refer on to a homoeopath (P < 0.001 for all variables) than those
      GPs who prescribed less than once a month or never. The majority of GPs who
      prescribed homoeopathic medicines did so when conventional treatments had
      apparently failed (76%), while 94% also perceived homoeopathy to be safe.
      Frequent prescribers reported a more positive attitude towards homoeopathic
      medicines than those who prescribed less frequently. Non-prescribers reported a
      lack of proven efficacy and lack of training as the main reasons for not
      prescribing homoeopathic medicines (55% and 79%, respectively). However non
      prescribers from within homoeopathic prescribing practices reported a more
      favourable attitude in general towards homoeopathy and less resistance towards
      prescribing in the future than non-prescribers from practices where none of the
      partners practiced homoeopathy. CONCLUSIONS: In primary care paediatric
      prescribing of homoeopathic medicines most commonly occurs for self-limiting
      conditions in infants less than 1 year of age. Although the current level of
      homoeopathic prescribing is low, the widespread use in the community suggests
      that at least some knowledge of the main indications for homoeopathy and the
      preparations used would be of benefit to registered medical practitioners.

PMID- 15948943
TI  - The potential of UK clinical databases in enhancing paediatric medication
      research.
AB  - The research potential of many UK clinical databases is not being realized. A
      recent report published by the Royal College of Paediatrics & Child Health stated
      that there is a need to build research capacity and support in the area of
      paediatric pharmacology, with specific emphasis on the use of clinical databases.
      This article presents the databases available in the UK for medication research
      and gives some examples of paediatric studies conducted. The databases discussed
      include the Prescription Pricing Authority database, the General Practice
      Research Database, IMS Health databases (Medical Data Index, MIDAS Prescribing
      Insights, Disease-Analyser-Mediplus) and the Yellow Card Scheme. Other databases
      such as the Medicines Monitoring Unit (MEMO) and the Scottish Primary Care
      Computer System also have research potential in paediatric pharmacoepidemiology,
      but their population sizes are relatively small.

PMID- 15948944
TI  - Maintaining a healthy SPANC balance through regulatory and mutational adaptation.
AB  - Stress protection is an important but costly contributor to bacterial survival.
      Two distinct forms of environmental protection share a common cost and a
      significant species-wide variability. Porin-mediated outer membrane permeability
      and the RpoS-controlled general stress response both involve a trade-off between
      self-preservation and nutritional competence, called the SPANC balance.
      Interestingly, different Escherichia coli strains exhibit distinct settings of
      the SPANC balance. It is tilted towards high stress resistance and a restricted
      diet in some isolates whereas others have broader nutritional capability and
      better nutrient affinity but lower levels of resistance. Growth- or stress
      related selective pressures working in opposite directions (antagonistic
      pleiotropy) result in polymorphisms affecting porins and RpoS. Consequently,
      these important cellular components are present at distinct concentrations in
      different isolates. A generalized hypothesis to explain bacterial adaptation,
      based on the SPANC investigations, is offered. A holistic approach to bacterial
      adaptation, involving a gamut of regulation and mutation, is likely to be the
      norm in broadening the capabilities of a species. Indeed, there is unlikely to be
      a standard regulatory setting typical for all members of a species. Gene
      regulation provides a limited fine control for maintaining the right level of
      adaptation in a particular niche but mutational changes provide the coarse
      control for adaptation between the species-wide environments of free-living
      bacteria.

PMID- 15948945
TI  - Spatial arrangement and macrodomain organization of bacterial chromosomes.
AB  - Recent developments in fluorescence microscopy have shown that bacterial
      chromosomes have a defined spatial arrangement that preserves the linear order of
      genes on the genetic map. These approaches also revealed that large portions of
      the chromosome in Escherichia coli or Bacillus subtilis are concentrated in the
      same cellular space, suggesting an organization as large regions defined as
      macrodomains. In E. coli, two macrodomains of 1 Mb containing the replication
      origin (Ori) and the replication terminus (Ter) have been shown to relocalize at
      specific steps of the cell cycle. A genetic analysis of the collision probability
      between distant DNA sites in E. coli has confirmed the presence of macrodomains
      by revealing the existence of large regions that do not collide with each other.
      Two macrodomains defined by the genetic approach coincide with the Ori and Ter
      macrodomains, and two new macrodomains flanking the Ter macrodomain have been
      identified. Altogether, these results indicate that the E. coli chromosome has a
      ring organization with four structured and two less-structured regions.
      Implications for chromosome dynamics during the cell cycle and future prospects
      for the characterization and understanding of macrodomain organization are
      discussed.

PMID- 15948946
TI  - PpsR: a multifaceted regulator of photosynthesis gene expression in purple
      bacteria.
AB  - Purple bacteria control the level of expression and the composition of their
      photosystem according to light and redox conditions. This control involves
      several regulatory systems that have been now well characterized. Among them, the
      PpsR regulator plays a central role, because it directly or indirectly controls
      the synthesis of all of the different components of the photosystem. In this
      review, we report our knowledge of the PpsR protein, highlighting the diversity
      of its mode of action and focusing on the proteins identified in four model
      purple bacteria (Rhodobacter capsulatus, Rhodobacter sphaeroides, Rubrivivax
      gelatinosus, Bradyrhizobium ORS278). This regulator exhibits unique regulatory
      features in each bacterium: it can activate and/or repress the expression of
      photosynthesis genes, its activity can be modulated or not by the redox
      conditions, it can interact with other specific regulators and therefore be
      involved differently in light and/or redox regulatory circuits.

PMID- 15948947
TI  - Genetic and physiological responses of Bacillus subtilis to metal ion stress.
AB  - Metal ion homeostasis is regulated principally by metalloregulatory proteins that
      control metal ion uptake, storage and efflux genes. We have used transcriptional
      profiling to survey Bacillus subtilis for genes that are rapidly induced by
      exposure to high levels of metal ions including Ag(I), Cd(II), Cu(II), Ni(II) and
      Zn(II) and the metalloid As(V). Many of the genes affected by metal stress were
      controlled by known metalloregulatory proteins (Fur, MntR, PerR, ArsR and CueR).
      Additional metal-induced genes are regulated by two newly defined metal-sensing
      ArsR/SmtB family repressors: CzrA and AseR. CzrA represses the CadA efflux ATPase
      and the cation diffusion facilitator CzcD and this repression is alleviated by
      Zn(II), Cd(II), Co(II), Ni(II) and Cu. CadA is the major determinant for Cd(II)
      resistance, while CzcD protects the cell against elevated levels of Zn(II), Cu,
      Co(II) and Ni(II). AseR negatively regulates itself and AseA, an As(III) efflux
      pump which contributes to arsenite resistance in cells lacking a functional ars
      operon. Our results extend the range of identified effectors for the As(III)
      sensor ArsR to include Cd(II) and Ag(I) and for the Cu-sensor CueR to include
      Ag(I) and, weakly, Cd(II) and Zn(II). In addition to systems dedicated to metal
      homeostasis, specific metal stresses also strongly induced pathways related to
      cysteine, histidine and arginine metabolism.

PMID- 15948948
TI  - Characterization of Chlamydia MurC-Ddl, a fusion protein exhibiting D-alanyl-D
      alanine ligase activity involved in peptidoglycan synthesis and D-cycloserine
      sensitivity.
AB  - Recent characterization of chlamydial genes encoding functional peptidoglycan
      (PG)-synthesis proteins suggests that the Chlamydiaceae possess the ability to
      synthesize PG yet biochemical evidence for the synthesis of PG has yet to be
      demonstrated. The presence of D-amino acids in PG is a hallmark of bacteria.
      Chlamydiaceae do not appear to encode amino acid racemases however, a D-alanyl-D
      alanine (D-Ala-D-Ala) ligase homologue (Ddl) is encoded in the genome. Thus, we
      undertook a genetics-based approach to demonstrate and characterize the D-Ala-D
      Ala ligase activity of chlamydial Ddl, a protein encoded as a fusion with MurC.
      The full-length murC-ddl fusion gene from Chlamydia trachomatis serovar L2 was
      cloned and placed under the control of the arabinose-inducible ara promoter and
      transformed into a D-Ala-D-Ala ligase auxotroph of Escherichia coli possessing
      deletions of both the ddlA and ddlB genes. Viability of the E.
      coliDeltaddlADeltaddlB mutant in the absence of exogenous D-Ala-D-Ala dipeptide
      became dependent on the expression of the chlamydial murC-ddl thus demonstrating
      functional ligase activity. Domain mapping of the full-length fusion protein and
      site-directed mutagenesis of the MurC domain revealed that the structure of the
      full fusion protein but not MurC enzymatic activity was required for ligase
      activity in vivo. Recombinant MurC-Ddl exhibited substrate specificity for D-Ala.
      Chlamydia growth is inhibited by D-cycloserine (DCS) and in vitro analysis
      provided evidence for the chlamydial MurC-Ddl as the target for DCS sensitivity.
      In vivo sensitivity to DCS could be reversed by addition of exogenous D-Ala and D
      Ala-D-Ala. Together, these findings further support our hypothesis that PG is
      synthesized by members of the Chlamydiaceae family and suggest that D-amino
      acids, specifically D-Ala, are present in chlamydial PG.

PMID- 15948949
TI  - Transcriptional regulation of the one-carbon metabolism regulon in Saccharomyces
      cerevisiae by Bas1p.
AB  - The mechanisms mediating responses to glycine withdrawal in budding yeast were
      studied using a genome-wide profiling approach. A striking pattern of repressed
      expression of genes with an enrichment for those involved in one-carbon
      metabolism and AMP biosynthesis was revealed. Sequence analysis of the promoters
      for the most severely repressed genes identified a conserved sequence, TGACTC, a
      known binding site for the transcription factors Gcn4p and Bas1p. Loss of BAS1
      abolished or significantly reduced the repression of these genes in response to
      glycine removal but this phenotype was much less apparent in the absence of BAS2
      or GCN4. Addition of a Bas1p-LexA fusion protein to a strain with a LexAop-LacZ
      fusion showed a strong glycine effect both in a BAS2 and a bas2 background. A
      Bas1p-VP16 fusion protein activated expression in a bas1bas2 strain but no
      glycine effect was observed while a Bas1p-Bas2p fusion protein activated
      expression to a lesser extent with a slight stimulation by glycine. These results
      suggest that glycine affects Bas1p activation of transcription rather than DNA
      binding and that Bas2p is not required for this affect. Glycine withdrawal
      repressed many of the same genes as addition of adenine, a process known to be
      dependent on Bas1p. However, the glycine response is independent of adenine
      repression, because glycine regulation occurs normally in ade strains. We did not
      see any difference in the degree of stimulation by glycine in the presence or
      absence of adenine even in Ade+ strains. Glycine regulation was also found to be
      dependent on an intact SHM2 gene, which encodes cytoplasmic serine
      hydroxymethyltransferase. A reporter plasmid containing a DNA sequence from the
      GCV2 promoter which confers glycine regulation on heterologous genes was
      introduced into the yeast deletion set to screen for genes required for glycine
      regulation. A number of genes, including BAS1 were required for activation by
      glycine but only the SHM2 gene was required for repression in the absence of
      glycine. We also showed that regulation of the SHM2 promoter by glycine requires
      Bas1p but not Bas2p or Gcn4p using a beta-galactosidase reporter. The response of
      the promoter to glycine required an intact SHM2 gene but was restored in a shm2
      strain by addition of formate to the medium.

PMID- 15948950
TI  - Genetic analysis of the Legionella pneumophila DotB ATPase reveals a role in type
      IV secretion system protein export.
AB  - The pulmonary pathogen Legionella pneumophila uses the Dot/Icm type IV secretion
      system (T4SS) to replicate inside host cells. This apparatus translocates
      proteins into macrophages to alter their endocytic pathway and enable bacterial
      growth. Although the secretion ATPase DotB is critical for T4SS function, its
      specific role in type IV secretion remains undefined. Due to similarity to the
      VirB11 and PilT ATPases, DotB has been proposed to play a role in assembly of the
      T4SS, retraction of pili and/or export of substrates. With the goal of
      understanding the protein's function(s), we isolated and characterized 30 dotB
      alleles using a variety of phenotypic and biochemical assays. Twenty-four of
      these alleles possess several dot/icm mutant phenotypes, including a complete
      lack of intracellular replication, plasmid mobilization and contact-dependent
      cytotoxicity. These 24 non-functional alleles fall into three classes: those with
      a known biochemical defect, those with a predicted enzymatic defect and those
      with an unknown defect. Six other alleles display partial activity in dot/icm
      phenotypic assays, thus constituting a fourth class. Two mutants in this class
      are unable to export a subset of T4SS substrates, providing the first evidence
      for a DotB function in substrate export and suggesting a possible role in
      substrate selection.

PMID- 15948951
TI  - The PhoP/PhoQ system controls the intramacrophage type three secretion system of
      Salmonella enterica.
AB  - Spi/Ssa is a unique type three secretion system that functions exclusively when
      Salmonella enterica is inside eukaryotic cells. Expression of the Spi/Ssa system
      and its secreted effectors is dependent on SsrB/SpiR, a two-component regulatory
      system encoded in the SPI-2 pathogenicity island that also harbours the spi/ssa
      genes. Here we determine that the PhoP/PhoQ two-component system controls the
      intramacrophage expression of spi/ssa genes by regulating the SsrB/SpiR system.
      We establish that PhoP regulates transcription of the response regulator SsrB and
      demonstrate binding of the PhoP protein to the ssrB promoter both in vivo using
      chromatin immunoprecipitation in Salmonella-infected macrophages, and in vitro
      using purified PhoP protein. We show that PhoP controls the SpiR sensor post
      transcriptionally and identify a region in the 5' untranslated region of the spiR
      message that is required for this effect. The demonstration that the PhoP/PhoQ
      system is directly involved in the regulation of the SPI-2 pathogenicity island
      highlights PhoP/PhoQ's central role in Salmonella virulence. We suggest that
      different regulatory systems convey distinct signals over time to produce the
      SsrB/SpiR system, which then modulates expression of the Spi/Ssa apparatus and
      secreted effectors.

PMID- 15948952
TI  - RecN protein and transcription factor DksA combine to promote faithful
      recombinational repair of DNA double-strand breaks.
AB  - In rapidly dividing bacterial cells, the machinery for repair of DNA double
      strand breaks has to contend not only with the forces driving replication and
      transmission of the DNA but also its transcription. By exploiting I-SceI homing
      endonuclease to break the Escherichia coli chromosome at one or more defined
      locations, we have been able to investigate how these processes are co-ordinated
      and repair is accomplished. When breaks are induced at a single site, the SOS
      inducible RecN protein and the transcription factor DksA combine to promote
      efficient repair. When induced at two or more, distantly located sites, RecN
      becomes almost indispensable. Many cells that do survive have extensive deletions
      of sequences flanking the break, with end points often coinciding with imperfect
      repeat elements. These findings herald a much greater complexity for chromosome
      repair than suggested by current mechanistic models and reveal a role for RecN in
      protecting the chromosome from break-induced chromosome rearrangements.

PMID- 15948953
TI  - Inactivation of patS and hetN causes lethal levels of heterocyst differentiation
      in the filamentous cyanobacterium Anabaena sp. PCC 7120.
AB  - Summary In the filamentous cyanobacterium Anabaena sp. PCC 7120 patS and hetN
      suppress the differentiation of vegetative cells into nitrogen-fixing heterocysts
      to establish and maintain a pattern of single heterocysts separated by
      approximately 10 undifferentiated vegetative cells. Here we show that the patS-
      and hetN-dependent suppression pathways are the only major factors that prevent
      vegetative cells from differentiating into heterocysts when a source of ammonia
      is not present. The patS and hetN pathways are independent of each other, and
      inactivation of both patS and hetN leads to differentiation of almost all cells
      of a filament in the absence of a source of fixed nitrogen, compared with
      approximately 9% in the wild type. Complete differentiation of filaments also
      occurs when nitrate is supplied as a source of fixed nitrogen, conditions that do
      not induce differentiation of wild-type filaments. However, ammonia is still
      capable of suppressing differentiation. The percentage of cells that
      differentiate into heterocysts appears to be a function of time when a source of
      fixed nitrogen is absent or a function of growth phase when nitrate is supplied.
      Although differentiation proceeds unchecked in the absence of patS and hetN
      expression, differentiation is asynchronous and non-random.

PMID- 15948954
TI  - Identification of the membrane penetrating domain of Vibrio cholerae cytolysin as
      a beta-barrel structure.
AB  - Vibrio cholerae cytolysin (VCC) is an oligomerizing pore-forming toxin that is
      related to cytolysins of many other Gram-negative organisms. VCC contains six
      cysteine residues, of which two were found to be present in free sulphydryl form.
      The positions of two intramolecular disulphide bonds were mapped, and one was
      shown to be essential for correct folding of protoxin. Mutations were created in
      which the two free cysteines were deleted, so that single cysteine substitution
      mutants could be generated for site-specific labelling. Employment of polarity
      sensitive fluorophores identified amino acid side-chains that formed part of the
      pore-forming domain of VCC. The sequence commenced at residue 311, and was
      deduced to form a beta-barrel in the assembled oligomer with the subsequent odd
      numbered residues facing the lipid bilayer and even-numbered residues facing the
      lumen. Pro328/Lys329 were tentatively identified as the position at which the
      sequence turns back into the membrane and where the antiparallel beta-strand
      commences. This was deduced from fluorimetric analyses combined with experiments
      in which the pore was reversibly occluded by derivatization of sulphydryl groups
      with a bulky moiety. Our data support computer-based predictions that the
      membrane-permeabilizing amino acid sequence of VCC is homologous to the beta
      barrel-forming sequence of staphylococcal cytolysins and identify the beta-barrel
      as a membrane-perforating structure that is highly conserved in evolution.

PMID- 15948955
TI  - Mapping of essential replication functions of the linear plasmid lp17 of B.
      burgdorferi by targeted deletion walking.
AB  - The genome of the Lyme disease pathogen Borrelia burgdorferi strain B31 MI
      includes one linear chromosome, 10 circular and 12 linear plasmids. Members of
      four paralogous gene families, revealed by genome sequencing, have been suggested
      as replication/partition functions for both the linear and circular plasmids.
      Some of these genes have been experimentally shown to be essential for the
      replication of the B. burgdorferi replicons that encode them. In this study, we
      located the region essential for replication of lp17, the second smallest linear
      plasmid in B. burgdorferi. We used a novel in vivo method, targeted deletion
      walking, to systematically delete DNA from either the left or right end of lp17.
      We report that the region essential for replication of lp17 is 1.8 kb (bp 7946
      9766) and contains only one intact open reading frame (BBD14). Expression of
      BBD14 is required for the replication, suggesting that it is the replication
      initiator for lp17. The BBD14 protein is a member of paralogous family (PF) 62
      and we present the first experimental evidence for the role of a PF 62 member.
      Adjacent non-coding sequences are also required, suggesting that the origin lies
      at least partially outside the coding region. Surprisingly, deletion of BBD21,
      the ParA orthologue (PF 32), had little effect upon plasmid stability or
      incompatibility. Finally, data are presented suggesting that lp17 replication
      occurs preferentially on a linear rather than a circular DNA molecule.

PMID- 15948956
TI  - An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni
      inferred from the structure of an extracytoplasmic solute receptor protein.
AB  - Campylobacter jejuni is a Gram-negative food-borne pathogen associated with
      gastroenteritis in humans as well as cases of the autoimmune disease Guillain
      Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic
      pathway for the use of sugars as a carbon source. This suggests an increased
      reliance on amino acids as nutrients and indeed the genome sequence of this
      organism indicates the presence of a number of amino acid uptake systems. Cj0982,
      also known as CjaA, is a putative extracytoplasmic solute receptor for one such
      uptake system as well as a major surface antigen and vaccine candidate. The
      crystal structure of Cj0982 reveals a two-domain protein with density in the
      enclosed cavity between the domains that clearly defines the presence of a bound
      cysteine ligand. Fluorescence titration experiments were used to demonstrate that
      Cj0982 binds cysteine tightly and specifically with a K(d) of approximately 10(
      7) M consistent with a role as a receptor for a high-affinity transporter. These
      data imply that Cj0982 is the binding protein component of an ABC-type cysteine
      transporter system and that cysteine uptake is important in the physiology of C.
      jejuni.

PMID- 15948957
TI  - Protein O-mannosylation is crucial for cell wall integrity, septation and
      viability in fission yeast.
AB  - Protein O-mannosyltransferases (PMTs) initiate the assembly of O-mannosyl
      glycans, which are of fundamental importance in eukaryotes. The PMT family, which
      is classified into PMT1, PMT2 and PMT4 subfamilies, is evolutionarily conserved.
      Despite the fact that PMTs are crucial for viability of baker's yeast as well as
      of mouse, recent studies suggested that there are significant differences in the
      organization and properties of the O-mannosylation machinery between yeasts and
      mammals. In this study we identified and characterized the PMT family of the
      archaeascomycete Schizosaccharomyces pombe. Unlike Saccharomyces cerevisiae where
      the PMT family is highly redundant, in S. pombe only one member of each PMT
      subfamily is present, namely, oma1+ (protein O-mannosyltransferase), oma2+ and
      oma4+. They all act as protein O-mannosyltransferases in vivo. oma1+ and oma2+
      form heteromeric protein complexes and recognize different protein substrates
      compared to oma4+, suggesting that similar principles underlie mannosyltransfer
      reaction in S. pombe and budding yeast. Deletion of oma2+, as well as
      simultaneous deletion of oma1+ and oma4+ is lethal. Characterization of the
      viable S. pombe oma1Delta and oma4Delta single mutants showed that a lack of O
      mannosylation results in abnormal cell wall and septum formation, thereby
      severely affecting cell morphology and cell-cell separation.

PMID- 15948958
TI  - Plasmodium berghei ookinetes bind to Anopheles gambiae and Drosophila
      melanogaster annexins.
AB  - Using a proteomic approach we identified polypeptides from Anopheles gambiae and
      Drosophila melanogaster protein extracts that selectively bind purified
      Plasmodium berghei ookinetes in vitro; these were two and three distinct
      polypeptides, respectively, with an apparent molecular weight of about 36 kDa.
      Combining two-dimensional electrophoresis and MALDI-TOF (matrix-associated laser
      desorption ionization time of flight) mass spectrometry we determined that the
      polypeptides correspond to isomorphs of the annexin B11 protein of the fruit fly.
      When protein extracts derived from A. gambiae and D. melanogaster tissue culture
      cells were further fractionated, the binding activity matching the annexin
      protein could be localized in the fraction derived from cell membranes in both
      diptera. Antibody staining showed that annexin also binds to ookinetes during the
      invasion of the mosquito midgut. Finally, inclusion of antiannexin antisera in a
      mosquito blood meal impaired parasite development, suggesting a facilitating role
      for annexins in the infection of the mosquito by Plasmodium.

PMID- 15948959
TI  - Novel relationships among DNA methylation, histone modifications and gene
      expression in Ascobolus.
AB  - By studying Ascobolus strains methylated in various portions of the native met2
      gene or of the hph transgene, we generalized our previous observation that
      methylation of the downstream portion of a gene promotes its stable silencing and
      triggers the production of truncated transcripts which rarely extend through the
      methylated region. In contrast, methylation of the promoter region does not
      promote efficient gene silencing. The chromatin state of met2 methylated strains
      was investigated after partial micrococcal nuclease (MNase) digestion. We show
      that MNase sensitive sites present along the unmethylated regions are no longer
      observed along the methylated ones. These chromatin changes are not resulting
      from the absence of transcription. They are associated, in both met2 and hph,
      with modifications of core histones corresponding, on the N terminus of histone
      H3, to an increase of dimethylation of lysine 9 and a decrease of dimethylation
      of lysine 4. Contrary to other organisms, these changes are independent of the
      transcriptional state of the genes, and furthermore, no decrease in acetylation
      of histone H4 is observed in silenced genes.

PMID- 15948960
TI  - Salmonella enterica serotype Typhimurium MisL is an intestinal colonization
      factor that binds fibronectin.
AB  - MisL is an autotransporter protein encoded by Salmonella pathogenicity island 3
      (SPI3). To investigate the role of MisL in Salmonella enterica serotype
      Typhimurium (S. Typhimurium) pathogenesis, we characterized its function during
      infection of mice and identified a host receptor for this adhesin. In a mouse
      model of S. Typhimurium intestinal persistence, a misL mutant was shed with the
      faeces in significantly lower numbers than the wild type and was impaired in its
      ability to colonize the cecum. Previous studies have implicated binding of
      extracellular matrix proteins as a possible mechanism for S. Typhimurium
      intestinal persistence. A gluthathione-S-transferase (GST) fusion protein to the
      MisL passenger domain (GST-MisL(29-281)) was constructed to investigate binding
      to extracellular matrix proteins. In a solid-phase binding assay the purified GST
      MisL(29-281) fusion protein bound to fibronectin and collagen IV, but not to
      collagen I. MisL expression was not detected by Western blot in S. Typhimurium
      grown under standard laboratory conditions. However, when expression of the
      cloned misL gene was driven by the Escherichia coli arabinose promoter, MisL
      could be detected in the S. Typhimurium outer membrane by Western blot and on the
      bacterial cell surface by flow cytometry. Expression of MisL enabled S.
      Typhimurium to bind fibronectin to its cell surface, resulting in attachment to
      fibronectin-coated glass slides and in increased invasiveness for human
      epithelial cells derived from colonic carcinoma (T84 cells). These data identify
      MisL as an extracellular matrix adhesin involved in intestinal colonization.

PMID- 15948961
TI  - Structural basis for segmental gene conversion in generation of Anaplasma
      marginale outer membrane protein variants.
AB  - Bacterial pathogens in the genus Anaplasma generate surface coat variants by gene
      conversion of chromosomal pseudogenes into single-expression sites. These
      pseudogenes encode unique surface-exposed hypervariable regions flanked by
      conserved domains, which are identical to the expression site flanking domains.
      In addition, Anaplasma marginale generates variants by recombination of
      oligonucleotide segments derived from the pseudogenes into the existing
      expression site copy, resulting in a combinatorial increase in variant diversity.
      Using the A. marginale genome sequence to track the origin of sequences
      recombined into the msp2 expression site, we demonstrated that the complexity of
      the expressed msp2 increases during infection, reflecting a shift from
      recombination of the complete hypervariable region of a given pseudogene to
      complex mosaics with segments derived from hypervariable regions of different
      pseudogenes. Examination of the complete set of 1183 variants with segmental
      changes revealed that 99% could be explained by one of the recombination sites
      occurring in the conserved flanking domains and the other within the
      hypervariable region. Consequently, we propose an 'anchoring' model for segmental
      gene conversion whereby the conserved flanking sequences tightly align and anchor
      the expression site sequence to the pseudogene. Associated with the recombination
      sites were deletions, insertions and substitutions; however, these are a
      relatively minor contribution to variant generation as these occurred in less
      than 2% of the variants. Importantly, the anchoring model, which can account for
      more variants than a strict segmental sequence identity mechanism, is consistent
      with the number of msp2 variants predicted and empirically identified during
      persistent infection.

PMID- 15948962
TI  - The Aspergillus nidulans sldI(RAD50) gene interacts with bimE(APC1), a homologue
      of an anaphase-promoting complex subunit.
AB  - The Mre11-Rad50-Nbs1 protein complex has emerged as a central component in the
      human cellular DNA damage response, and recent observations suggest that these
      proteins are at least partially responsible for the linking of DNA damage
      detection to DNA repair and cell cycle checkpoint functions. We have identified
      Aspergillus nidulans sldI1444D mutant in a screen for dynein synthetic lethals.
      The sldI(RAD50) gene was cloned by complementation of the sporulation deficiency
      phenotype of this mutant. A transversion G-->C at the position 2509 (Ala-692-Pro
      amino acid change) in the sldI1444D mutant causes sensitivity to several DNA
      damaging agents. The mutation sldI1 occurs at the CXXC hinge domain of Rad50. We
      have deleted part of the coiled-coil and few amino acids of the Rad50-Mre11
      interaction region and assessed several phenotypic traits in this deletion
      strain. Besides sensitivity to a number of DNA-damaging agents, this deletion
      strain is also impaired in the DNA replication checkpoint response, and in
      ascospore viability. There is no delay of the S-phase when germlings of both sldI
      (RAD50) and mreA(MRE11) inactivation strains were exposed to the DNA damage
      caused by bleomycin. Transformation experiments and Southern blot analysis
      indicate homologous recombination is dependent on scaA(NBS1) function in the
      Mre11 complex. There are epistatic and synergistic interactions between sldI(
      RAD50) and bimE(APC1) at S-phase checkpoints and response to hydroxyurea and UV
      light. Our results suggest a possible novel feature of the Mre11 complex in A.
      nidulans, i.e. a relationship with bimE (APC1).

PMID- 15948964
TI  - Post-transcriptional control of a glucoamylase gene from Trichoderma harzianum
      under stress conditions.
AB  - We have examined the regulation of Trichoderma harzianum glucoamylase gene
      (Gla66) in response to different growth conditions. Transcription of the Gla66
      gene is initiated from two different sites, yielding two transcripts of 2.1 kb
      and 2.6 kb respectively. The 2.1 kb mRNA (ST) encodes for an extracellular
      glucoamylase of 66 kDa. This protein shows the domains conserved in other fungal
      glucoamylases: a signal peptide responsible for protein secretion and a catalytic
      domain, both joined by a linker region. The longest transcript (LT) is
      untranslated, it contains an unusually extended 5'-untranslated region and is
      transcribed under stress and growth limiting conditions. The translational
      control of LT could be defined by the presence of four upstream open reading
      frames (uORFs) in its 5'-leader sequence. The analysis of these uORFs in a yeast
      heterologous system shows that two of these uORFs prevent the Gla66 translation
      under unfavourable growth conditions, when the LT transcript is accumulated.

PMID- 15948963
TI  - The ClpX chaperone modulates assembly of the tubulin-like protein FtsZ.
AB  - Summary Assembly of the tubulin-like cytoskeletal protein FtsZ into a ring
      structure establishes the location of the nascent division site in prokaryotes.
      Factors that modulate FtsZ assembly are essential for ensuring the precise
      spatial and temporal regulation of cytokinesis. We have identified ClpX, the
      substrate recognition subunit of the ClpXP protease, as an inhibitor of FtsZ
      assembly in Bacillus subtilis. Genetic data indicate that ClpX but not ClpP
      inhibits FtsZ-ring formation in vivo. In vitro, ClpX inhibits FtsZ assembly in a
      ClpP-independent manner through a mechanism that does not require ATP hydrolysis.
      Together our data support a model in which ClpX helps maintain the cytoplasmic
      pool of unassembled FtsZ that is required for the dynamic nature of the
      cytokinetic ring. ClpX is conserved throughout bacteria and has been shown to
      interact directly with FtsZ in Escherichia coli. Thus, we speculate that ClpX
      functions as a general regulator of FtsZ assembly and cell division in a wide
      variety of bacteria.

PMID- 15948965
TI  - Multiple Rieske genes in prokaryotes: exchangeable Rieske subunits in the
      cytochrome bc-complex of Rubrivivax gelatinosus.
AB  - Bacterial cytochrome bc1-complex encoded by the petABC operon consists of three
      subunits, the Rieske iron-sulphur protein, the b-type cytochrome, and the c1-type
      cytochrome. Disruption of the petA gene of Rubrivivax gelatinosus is not lethal
      under photosynthetic growth conditions. However, deletion of both petA and petB
      results in a photosynthesis-deficient strain, suggesting the presence of a second
      gene encoding a Rieske protein and rescuing a functional cytochrome bc1-complex
      in the PETA1 mutant. The corresponding petA2 gene was identified and the PETA2
      mutant could also grow under photosynthetic conditions. The double mutant PETA12,
      however, was unable to grow photosynthetically. The presence of a photo-induced
      cyclic electron transfer was tested by monitoring the kinetics of cytochrome
      photo-oxidation on intact cells; the data confirm the capacity of petA2 to
      replace petA1 in the bc1-complex to support photosynthesis. Soluble forms of both
      PetA1 and PetA2 Rieske proteins were purified from Escherichia coli and found to
      contain correctly inserted [2Fe-2S] clusters. Electron paramagnetic resonance
      (EPR) spectroscopy and midpoint potential measurements showed typical [2Fe-2S]
      signals and E(m) values of +275 mV for both Rieske proteins. The high amino acid
      sequence similarity and the obtained midpoint potential values argue for a
      functional role of these proteins in the cytochrome bc1-complex. The presence of
      duplicated Rieske genes is not restricted to R. gelatinosus. Phylogenetic trees
      of Rieske genes from Rubrivivax and other proteobacteria as well as from
      cyanobacteria were reconstructed. On the basis of the phylogenetic analyses,
      differing evolutionary origins of duplicated Rieske genes in proteo- and
      cyanobacteria are proposed.

PMID- 15948966
TI  - Convergent evolution of hydroxylation mechanisms in the fungal kingdom:
      molybdenum cofactor-independent hydroxylation of xanthine via alpha-ketoglutarate
      dependent dioxygenases.
AB  - The xanthine oxidases and dehydrogenases are among the most conserved enzymes in
      all living kingdoms. They contain the molybdopterin cofactor Moco. We show here
      that in the fungi, in addition to xanthine dehydrogenase, a completely different
      enzyme is able to catalyse the oxidation of xanthine to uric acid. In Aspergillus
      nidulans this enzyme is coded by the xanA gene. We have cloned the xanA gene and
      determined its sequence. A deletion of the gene has the same phenotype as the
      previously known xanA1 miss-sense mutation. Homologues of xanA exist only in the
      fungal kingdom. We have inactivated the cognate gene of Schizosaccharomyces pombe
      and this results in strongly impaired xanthine utilization as a nitrogen source.
      We have shown that the Neurospora crassa homologue is functionally equivalent to
      xanA. The enzyme coded by xanA is an alpha-ketoglutarate- and Fe(II)-dependent
      dioxygenase which shares a number of properties with other enzymes of this group.
      This work shows that only in the fungal kingdom, an alternative mechanism of
      xanthine oxidation, not involving Moco, has evolved using the dioxygenase
      scaffold.

PMID- 15948967
TI  - Swi/SNF-GCN5-dependent chromatin remodelling determines induced expression of
      GDH3, one of the paralogous genes responsible for ammonium assimilation and
      glutamate biosynthesis in Saccharomyces cerevisiae.
AB  - It is accepted that Saccharomyces cerevisiae genome arose from complete
      duplication of eight ancestral chromosomes; functionally normal ploidy was
      recovered because of the massive loss of 90% of duplicated genes. There is
      evidence that indicates that part of this selective conservation of gene pairs is
      compelling to yeast facultative metabolism. As an example, the duplicated NADP
      glutamate dehydrogenase pathway has been maintained because of the differential
      expression of the paralogous GDH1 and GDH3 genes, and the biochemical
      specialization of the enzymes they encode. The present work has been aimed to the
      understanding of the regulatory mechanisms that modulate GDH3 transcriptional
      activation. Our results show that GDH3 expression is repressed in glucose-grown
      cultures, as opposed to what has been observed for GDH1, and induced under
      respiratory conditions, or under stationary phase. Although GDH3 pertains to the
      nitrogen metabolic network, and its expression is Gln3p-regulated, complete
      derepression is ultimately determined by the carbon source through the action of
      the SAGA and SWI/SNF chromatin remodelling complexes. GDH3 carbon-mediated
      regulation is over-imposed to that exerted by the nitrogen source, highlighting
      the fact that operation of facultative metabolism requires strict control of
      enzymes, like Gdh3p, involved in biosynthetic pathways that use tricarboxylic
      acid cycle intermediates.

PMID- 15948969
TI  - The role of CD91 and heat shock proteins in psoriasis.

PMID- 15948970
TI  - Psoriasis: dysregulation of innate immunity.
AB  - The current understanding of the function of natural killer (NK) T cells in
      innate immunity and their potential to control acquired specific immunity, as
      well as the remarkable efficacy of antitumour necrosis factor-alpha biological
      treatments in psoriasis, forces us to refine the current T-cell hypothesis of
      psoriasis pathogenesis, and to give credit to the role of innate immunity.
      Psoriasis might be envisioned to be a genetically determined triggered state of
      otherwise dormant innate immunity. This aggravated state of innate immunity is
      represented by the activity of NK T cells, dendritic cells, neutrophils and
      keratinocytes, leading to the recruitment and activation of preferentially type 1
      T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then
      are sensitive to the effects of T-cell activation and cytokine production,
      interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic
      inflammation of psoriatic lesions suggests that this might be due to a deficiency
      in downregulation processes (e.g. a defect in the regulatory T-cell repertoire)
      and/or the persistence of an unknown trigger resulting in an exaggerated innate
      immune response.

PMID- 15948971
TI  - Molecular aetiology and pathogenesis of basal cell carcinoma.
AB  - Recent insights into the cell biology of the epidermis and its appendages are
      transforming our understanding of the pathogenesis of basal cell carcinoma (BCC).
      The significant progress that has been made warrants a comprehensive review of
      the molecular and cellular pathology of BCC. The items addressed include
      environmental and genetic risk factors, the biology of the putative precursor
      cell(s), and the contribution of aberrations in processes such as apoptosis, cell
      proliferation, differentiation and signalling to carcinogenesis. Furthermore,
      established and novel treatment modalities are discussed with particular
      attention to future biological approaches.

PMID- 15948972
TI  - Ectopic expression of c-Myc in the skin affects the hair growth cycle and causes
      an enlargement of the sebaceous gland.
AB  - BACKGROUND: The hair follicle continually undergoes dynamic remodelling in a
      cyclical manner involving tightly coordinated patterns of cell proliferation,
      differentiation and apoptosis. The oncoprotein c-Myc is a key regulator of these
      events in epidermal keratinocytes, but its importance in the hair growth cycle
      has not previously been determined. OBJECTIVES: To determine the role of c-Myc in
      the hair growth cycle. METHODS: We characterized the hair follicle phenotype of
      transgenic mice that permit expression of a switchable form of c-Myc (c-Myc-ER)
      in the suprabasal epithelial layers of the epidermis and hair follicle. RESULTS:
      c-Myc activation increased epithelial cell proliferation in the outer root sheath
      and distal hair follicle, without any substantial alteration in levels of
      apoptosis. Moreover, chronic c-Myc activation resulted in marked
      desynchronization of the murine hair growth cycle, uncoupling of hair cycle
      related skin thickness and enlargement of the sebaceous gland. CONCLUSIONS: These
      data implicate c-Myc in the control of hair growth cycling and hair cycle-related
      epidermal and sebaceous gland homeostasis. We suggest that c-Myc may be
      activating follicular stem cells either directly or indirectly and that this has
      important implications for control of the 'hair cycle clock', hair growth and
      epidermal maintenance.

PMID- 15948973
TI  - Interferon (IFN)-gamma is a main mediator of keratinocyte (HaCaT) apoptosis and
      contributes to autocrine IFN-gamma and tumour necrosis factor-alpha production.
AB  - BACKGROUND: Apoptosis of keratinocytes or intestinal epithelial cells is an
      important pathophysiological mechanism of organ damage during acute graft-versus
      host disease. OBJECTIVES: To analyse in detail the mediators and their mutual
      interaction leading to keratinocyte apoptosis. METHODS: Experiments were
      performed using a keratinocyte cell line (HaCaT) and human skin explant cultures.
      RESULTS: Supernatants (SN) of major histocompatibility complex nonmatched mixed
      lymphocyte cultures (MLCs) induced apoptosis in HaCaT cells and also in
      keratinocytes from skin biopsies. Although both interferon (IFN)-gamma and Fas
      ligand (FasL) were detected in MLC-SN by enzyme-linked immunosorbent assay, the
      apoptosis-inducing capacity could be fully abrogated by neutralization of IFN
      gamma, but not by neutralization of FasL. Recombinant (r) IFN-gamma induced HaCaT
      keratinocyte apoptosis in a dose- and time-dependent manner. Induction of HaCaT
      apoptosis by rFasL alone was induced only at higher doses than present in MLC-SN,
      but apoptosis was dramatically enhanced in the presence of rIFN-gamma. Further
      synergistic effects with IFN-gamma in the induction of apoptosis were also
      observed with agonistic antitumour necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) receptor 2 antibody, soluble TRAIL and TNF-alpha.
      However, in contrast to FasL and TRAIL, TNF-alpha alone did not induce HaCaT
      apoptosis. Interleukin-1beta and lipopolysaccharide did not enhance the apoptosis
      inducing effect of IFN-gamma. Beside its apoptosis-inducing capacity in HaCaT
      cells, rIFN-gamma also induced autocrine IFN-gamma production, and combined
      treatment with IFN-gamma and TNF-alpha induced autocrine TNF-alpha production.
      Neutralization of autocrine IFN-gamma protected HaCaT cells from apoptosis.
      CONCLUSIONS: Taken together, our data suggest a central role for IFN-gamma in
      HaCaT keratinocyte apoptosis but also show the importance of co-acting mediators
      such as TNF-alpha, TRAIL and FasL, which potentiate the effect of paracrine and
      autocrine IFN-gamma and TNF-alpha release.

PMID- 15948974
TI  - A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis.
AB  - BACKGROUND: Erythrokeratodermia variabilis (EKV) is an autosomal dominant or
      recessive genodermatosis characterized by the coexistence of randomly occurring,
      transient, erythematous patches and hyperkeratosis of the skin. The disorder has
      been mapped to chromosome 1p35.1 but is genetically heterogeneous. EKV may be
      caused by pathogenic mutations in one of two neighbouring connexin genes, GJB3
      and GJB4, encoding the gap junction proteins Cx31 and Cx30.3, respectively.
      Twelve distinct mutations identified to date cluster either at the cytoplasmic
      amino-terminus or in the four transmembrane domains. OBJECTIVES: To report a
      large family with EKV and an unrelated sporadic case. METHODS: DNA amplification
      and mutation analysis, followed by denaturing high-performance liquid
      chromatography to confirm the segregation of the mutations in the two families
      with EKV. RESULTS: A novel, recurrent GJB3 mutation (625C-->T; L209F) was
      identified in the family with EKV and in the unrelated sporadic case.
      CONCLUSIONS: This mutation is the first to affect a conserved residue in the
      cytoplasmic carboxy-terminus of any connexin gene with a cutaneous phenotype,
      emphasizing its structural and/or functional importance.

PMID- 15948975
TI  - Mast cell tryptase and chymase in chronic leg ulcers: chymase is potentially
      destructive to epithelium and is controlled by proteinase inhibitors.
AB  - BACKGROUND: Numerous mast cells are present in chronic leg ulcers. Tryptase and
      chymase are the major mediators of mast cells, but their significance is mostly
      dependent on their activity. In addition, the proteinases may affect ulcer
      epithelialization. OBJECTIVES: To study levels and activity of tryptase and
      chymase in wash samples and biopsies from chronic leg ulcers and the possible
      effect of these proteinases on keratinocyte growth and adherence. METHODS: Wash
      samples were taken from 16 patients and a superficial shave biopsy was taken in
      eight of these patients; a second biopsy series was obtained from the edge of
      chronic venous leg ulcers (n = 6). RESULTS: Significant levels of soluble
      tryptase activity and histamine, but low levels of chymase activity, were
      measured in wash samples from chronic ulcers. No tryptase-inhibiting activity,
      but clear chymase-inhibiting activity, was detected in the wash samples. In
      superficial wound bed biopsies, relatively marked levels of chymase activity
      together with histamine and tryptase activity were detected. In the second biopsy
      series, about 80% of the mast cells belonged to the MC(TC) type (tryptase- and
      chymase-immunopositive). However, about 55-61% of the chymase-immunopositive
      cells displayed chymase activity and 64 +/- 17% of the tryptase-positive cells
      revealed immunoreactivity of alpha(1)-antichymotrypsin. As the activity of
      chymase and tryptase was detected in the ulcer base in a ratio of 1:8, a
      preparation containing both chymase and tryptase was partially purified from
      human skin yielding a similar activity ratio of 1:11-13. Treatment of fibronectin
      coated plastic surfaces with this preparation decreased the adherence of cultured
      human keratinocytes, this effect being attributable mainly to chymase. In 2-day
      cultures using growth factor/serum-deficient low- or high-calcium medium, the
      tryptase-chymase preparation inhibited the slow growth and at higher
      concentrations it even induced detachment of keratinocytes. This effect was
      attributed to chymase, and it was partially regulated by heparin and histamine.
      CONCLUSIONS: Even though chymase is partially inactivated in chronic leg ulcers,
      accumulated mast cells in the close proximity of the epithelium edge and their
      chymase may impair keratinocyte adherence and migration.

PMID- 15948976
TI  - Anxiety accelerates T-helper 2-tilted immune responses in patients with atopic
      dermatitis.
AB  - BACKGROUND: Stress, which mediates anxiety, worsens skin symptoms in patients
      with atopic dermatitis (AD). The contribution of anxiety to immune dysfunction,
      which plays a critical role in the pathogenesis of AD, requires clarification.
      OBJECTIVES: To examine the relationship between anxiety and atopy-relevant immune
      function in AD. METHODS: Eighty-five patients with AD and 58 normal individuals
      without a history of allergic disorders were enrolled in this study. To assess
      anxiety, the state-trait anxiety inventory was completed for both groups. In the
      AD group, measurements were made of SCORAD scores, serum IgE levels, itching
      (visual analogue scale), blood eosinophil count and T-helper (Th) 1/Th2 ratio in
      the peripheral blood. RESULTS: Anxiety was significantly higher among the
      subjects with AD than the normal subjects, and trait anxiety (TA) was higher than
      state anxiety (SA) in the AD group. Serum total IgE levels were correlated
      positively with TA and the TA/SA ratio and inversely with SA, and the Th1/Th2
      ratio was correlated inversely with TA and the TA/SA ratio. CONCLUSIONS: The
      patients with AD had higher anxiety levels than normal individuals, and those
      with a stronger perception of TA than SA showed enhanced serum IgE synthesis and
      Th2 shifting.

PMID- 15948977
TI  - Effect of vitiligo on self-reported health-related quality of life.
AB  - BACKGROUND: Vitiligo is a pigmentary disorder affecting at least 1% of the total
      population. Although the disease does not produce direct physical impairment, it
      may considerably influence the psychological well-being of the patients. It has
      been suggested that patients suffer from low self-esteem, poor body image and a
      poor quality of life. The majority of the studies on the psychosocial impact of
      vitiligo were conducted in the U.S.A. and England. OBJECTIVES: This study aims to
      quantify the burden of vitiligo by estimating health-related quality of life in
      the Dutch-speaking Belgian population (Flanders). This is compared with the level
      of disability caused by psoriasis in a similarly recruited population. It is also
      our purpose to detect those at risk of experiencing a poor quality of life and to
      identify variables that might predict this impairment. PATIENTS AND METHODS:
      Patients with vitiligo (n = 119) and 162 patients with psoriasis were included in
      a postal survey. In order to obtain a patient-based measurement of quality of
      life we used the Dermatology Life Quality Index (DLQI), a widely validated
      questionnaire that is easy to use and allows comparison between several skin
      disorders. Other survey questions were related to demographic data and disease
      related characteristics. RESULTS: We obtained excellent response rates in both
      patient groups. The overall mean DLQI score for vitiligo (4.95) was lower than
      that for psoriasis (6.26) (P = 0.01). Patients with vitiligo experienced
      significantly less impairment of life quality from the symptoms and treatment of
      the disease (P < 0.001). The highest individual mean scores in vitiligo were
      found for Q2 (feelings), Q4 (clothing), Q5 (social and leisure activities) and Q3
      (daily routine). The interaction of disease and sex on the DLQI score was highly
      significant (P = 0.001). While men with vitiligo scored significantly lower than
      men with psoriasis (P < 0.001), we found a comparable overall DLQI score for
      women in these disease groups. The number of consultations (P = 0.005) and
      severity of the disease (P < 0.001) were independently related to the DLQI.
      CONCLUSIONS: Our study quantifies the burden on the quality of life caused by
      vitiligo and indicates specific areas of patients' lives which are most affected
      by the disease. Sex, number of consultations and subjective disease severity
      independently predict the quality of life. The quality of life impairment in
      women affected with vitiligo equals the impairment caused by psoriasis in our
      study population. These results should awake the interest of physicians in this
      'cosmetic' disease, since appropriate treatment is likely to improve the quality
      of life of vitiligo patients.

PMID- 15948978
TI  - Tacrolimus decreases the expression of eotaxin, CCR3, RANTES and interleukin-5 in
      atopic dermatitis.
AB  - BACKGROUND: There is a lack of studies on the effect of tacrolimus on eosinophils
      and related molecules including eotaxin, CCR3, RANTES and interleukin (IL)-5.
      OBJECTIVES: To investigate the effects of tacrolimus on in vivo eosinophil counts
      and on the related molecules eotaxin, CCR3, RANTES and IL-5 in patients with
      atopic dermatitis (AD). METHODS: Lesional skin specimens and sera were obtained
      from 15 patients with AD and from 15 normal controls. For 8 weeks, the patients
      with AD applied 0.03% tacrolimus ointment to all affected areas twice daily.
      Blood sampling and skin biopsies were then repeated. We evaluated serum eotaxin
      and IL-5 levels, and tissue eotaxin, CCR3, RANTES and IL-5 levels. Additionally,
      tissue levels of eotaxin and CCR3 mRNA were measured. RESULTS: After treatment
      with topical tacrolimus twice daily for 8 weeks, significant decreases were found
      in serum IL-5 levels, immunoreactive cell counts of eotaxin, IL-5, CCR3 and
      RANTES in AD skin, and tissue eosinophil counts. However, the change in the serum
      eosinophil count was not statistically significant, and mRNA levels of eotaxin
      and CCR3 were not decreased significantly after treatment. CONCLUSIONS: Topical
      tacrolimus reduces the number of eosinophils in tissue and suppresses the
      expression of eotaxin, CCR3, RANTES and IL-5 related to proliferation,
      recruitment, activation and survival of eosinophils.

PMID- 15948979
TI  - Dual wavelength (532 and 633 nm) laser Doppler imaging of plaque psoriasis.
AB  - BACKGROUND: Increased blood flow occurs in plaques of psoriasis, and an increase
      in blood flow has been shown to occur in uninvolved skin adjacent to the active
      edge. OBJECTIVES: In order to gain more insight into the pathophysiology of the
      active edges of plaques of psoriasis, we investigated different components of the
      microcirculation in the lesional and nonlesional skin of patients with psoriasis,
      using dual wavelength laser Doppler imaging (LDI). METHODS: The cutaneous blood
      flow in 23 plaques on the forearms of 20 patients with chronic plaque psoriasis
      was recorded using dual wavelength LDI. Perfusion was determined within the
      plaque (P), in uninvolved skin adjacent to the plaque (A) and in nonadjacent skin
      (U). RESULTS: Perfusion in plaques was increased as imaged by either 633 nm (red
      wavelength) or 532 nm (green wavelength) compared with both adjacent and
      nonadjacent uninvolved skin: median (interquartile range) P/A(RED) = 3.7 (2.5
      4.9), P/A(GREEN) = 1.3 (1.2-1.6), P/U(RED) = 4.2 (2.7-6.1), P/U(GREEN) = 1.5 (1.3
      1.9). CONCLUSIONS: Vascular perfusion is increased within plaques of psoriasis
      compared with adjacent and nonadjacent uninvolved skin. The results suggest an
      area of increased perfusion in skin adjacent to plaques, when compared with
      nonadjacent skin, for both deeper (large) and superficial (small) vessels (imaged
      by 633 and 532 nm, respectively). We believe that this dual wavelength tool may
      be a suitable and useful way of assessing pathophysiology and treatment response
      in psoriasis.

PMID- 15948980
TI  - Serum interleukin-8 level is a more sensitive marker than serum interleukin-6
      level in monitoring the disease activity of oral lichen planus.
AB  - BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease.
      Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and
      inflammation. OBJECTIVES: To investigate whether serum IL-8 level was a more
      sensitive marker than serum IL-6 level in monitoring the disease activity of OLP
      and to assess whether IL-8 was a useful serum marker in evaluating the
      therapeutic effects of levamisole on OLP patients. METHODS: In this study, we
      used a solid phase, two-site sequential chemiluminescent immunometric assay to
      determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP,
      nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP
      patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal
      serum concentration were treated with levamisole for 0.5-6.0 months and their
      serum IL-6 and IL-8 levels were measured after treatment. RESULTS: We found that
      28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16)
      nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper
      normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142)
      EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the
      upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or
      IL-8 levels higher than the upper limit of normal serum concentration, treatment
      with levamisole for a period of 0.5-6.0 months could significantly reduce the
      mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P <
      0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/-
      17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001). CONCLUSIONS: Because
      measurement of the serum IL-8 level can detect more OLP patients with an abnormal
      serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude
      that serum IL-8 level is a more sensitive marker than serum IL-6 level in
      monitoring the disease activity of OLP. Levamisole can modulate both the serum IL
      6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker
      in evaluating the therapeutic effects of levamisole on OLP patients.

PMID- 15948981
TI  - Use of nonprescription topical steroids: patients' experiences.
AB  - BACKGROUND: Topical steroids became available, without prescription, in the U.K.
      in 1987, with hydrocortisone 1% cream first being licensed for irritant contact
      dermatitis and reactions to insect bites. Since then the number of indications
      for nonprescription hydrocortisone use has increased and clobetasone has also
      become available as an over-the-counter (OTC) medicine. Little has been reported
      about how OTC steroids are used by community pharmacy clients. OBJECTIVES: We
      determined how OTC topical steroids are applied by patients, their demographic
      profile, the products used and the conditions treated, how frequently products
      were applied and how regularly purchased. The extent to which off-label use takes
      place was explored. METHODS: A patient-completed questionnaire study was used in
      100 branches of a national pharmacy in Great Britain. RESULTS: Questionnaires
      were completed and returned by 315 clients (16%). Eczema (192 cases, 61%) and
      dermatitis (66 cases, 21%) were the conditions most frequently treated.
      Nottingham Eczema Severity Scores calculated for 228 eczema and dermatitis
      sufferers shows that 164 patients (72%) had mild eczema. Those with more severe
      eczema were more likely to use clobetasone than hydrocortisone. The use of
      topical steroids outside OTC marketing authorization guidelines was widespread;
      however, no patient reported any adverse effects or deterioration in condition
      following steroid use. CONCLUSIONS: OTC topical steroids are used mainly to treat
      eczema and dermatitis. Almost 50% of users treating these conditions exceed the
      limits of the rather restrictive OTC marketing authorization. Clinicians should
      be aware of the potential for adverse effects as a result of patients self
      medicating with hydrocortisone or clobetasone for an extended period.

PMID- 15948982
TI  - Lack of apoptosis of Sezary cells in the circulation following oral bexarotene
      therapy.
AB  - BACKGROUND: Apoptosis of malignant cells has been suggested as an important
      mechanism of the action of bexarotene in the treatment of cutaneous T-cell
      lymphoma (CTCL). OBJECTIVES: Our purpose was to examine the in vivo and in vitro
      responses of patients with Sezary syndrome treated with oral bexarotene and
      assess them for apoptosis of the Sezary cells. METHODS: Six patients with CTCL
      with circulating Sezary cells, participating in a clinical trial of oral
      bexarotene (300 mg m(-2) daily) were included in the study. Peripheral blood from
      the patients was analysed for in vivo and in vitro apoptosis. RESULTS: None of
      the six patients demonstrated in vivo apoptosis. In vitro apoptosis of Sezary
      cells was demonstrated in one patient following exogenous bexarotene.
      CONCLUSIONS: Apoptosis is not detectable in the circulation of patients with
      Sezary syndrome treated with bexarotene.

PMID- 15948983
TI  - Management of melanoma metastasis to the breast: case series and review of the
      literature.
AB  - BACKGROUND: Metastases to the breast from extramammary cancers are rare; melanoma
      is one of the malignancies that can metastasize to the breast. OBJECTIVES: To
      examine the records of a series of patients with a previous diagnosis of melanoma
      and a metastasis to the breast, and review the published literature of this
      condition. METHODS: We report details of eight female patients with breast
      metastases from melanoma seen over a 36-month period from 2001. All patients were
      female aged 28-84 years (median 58). The breast lump was investigated by core-cut
      biopsy or fine needle aspiration, with or without a mammogram. RESULTS: The time
      between diagnosis of the primary melanoma and the occurrence of a breast
      metastasis ranged from 13 to 180 months (median 62). In three patients the breast
      lump was the first sign of recurrence of melanoma. In three patients melanoma had
      previously relapsed in regional lymph nodes and in two patients it had already
      relapsed as locoregional and distant subcutaneous metastases before metastasizing
      to the breast. In two patients presenting via the breast clinic, the lump was
      subsequently confirmed on excision to be melanoma in an intramammary lymph node.
      In seven patients, a lumpectomy was performed after histological confirmation;
      one of these also had a level 1-3 axillary dissection. The eighth patient
      deteriorated clinically before further surgery was possible. Six patients
      developed further metastases within 1-5 months of breast lump detection. In one
      case a second 9 mm breast lump in the deeper tissue of the same breast was
      detected on a computed tomography scan and has been removed using stereotactic
      surgery. Four patients have died. CONCLUSIONS: Presentation is usually with a
      palpable mass without skin changes. Investigation must include histology or
      cytology to confirm the diagnosis. Management of melanoma metastasis to the
      breast is discussed; in this series it was surgical unless there were many
      metastases.

PMID- 15948984
TI  - Activation of dendritic antigen-presenting cells expressing common heat shock
      protein receptor CD91 during induction of psoriasis.
AB  - BACKGROUND: Psoriasis is a common and chronic relapsing inflammatory skin
      disorder. Although a role for T cells in mediating the induction and maintenance
      of psoriatic lesions is well established, mechanisms responsible for activation
      of T cells by antigen-presenting cells (APCs) during disease relapse are poorly
      understood. OBJECTIVES: (i) To determine whether expression of the common heat
      shock protein (HSP) receptor CD91 correlated with development of psoriasis in a
      mouse model of psoriasis, (ii) to characterize the lesional cells on which CD91
      was expressed, and (iii) to investigate whether CD91+ cells in psoriasis showed
      signs of activation. METHODS: Two systems were used in order to study the above
      mentioned objectives: (i) skin biopsies taken directly from patients with
      psoriasis (either psoriatic plaques or symptomless prepsoriatic skin) or from
      healthy donors, respectively, or (ii) (human) skin biopsies collected during
      development of psoriasis using a novel xenograft mouse model of psoriasis. The
      skin samples were then either processed for analysis by light microscopy, or
      labelled with fluorochrome-conjugated antibodies and analysed by confocal laser
      scanning microscopy. RESULTS: We observed a markedly increased number of CD91+
      cells which paralleled development of new psoriatic lesions in the psoriasis
      mouse model and in established psoriatic plaques compared with symptomless
      prepsoriatic or healthy skin. Morphology as well as cell-specific markers showed
      that CD91 was predominantly expressed by dermal dendritic APCs characterized by
      activation of nuclear factor-kappaB signalling and the presence of tumour
      necrosis factor-alpha, an important proinflammatory cytokine in the
      immunopathogenesis of psoriasis. In addition, HSP70, a ligand for CD91, was
      increased in keratinocytes in close vicinity to CD91-bearing APCs in psoriatic
      lesions. CONCLUSIONS: These findings indicate massive presence of CD91+ dendritic
      cells juxtaposed to lesional keratinocytes expressing HSP70, and suggest a novel
      pathophysiological pathway and therapeutic target for this chronic inflammatory
      skin disease.

PMID- 15948985
TI  - Oral pimecrolimus in the treatment of moderate to severe chronic plaque-type
      psoriasis: a double-blind, multicentre, randomized, dose-finding trial.
AB  - BACKGROUND: There is a need for safe and effective alternative treatments for
      patients with moderate to severe psoriasis. OBJECTIVES: Pimecrolimus is a
      calcineurin inhibitor that is being investigated in oral form for the treatment
      of psoriasis. PATIENTS AND METHODS: A double-blind, randomized, parallel-group,
      dose-finding study was performed. Healthy adult outpatients with moderate to
      severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral
      placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks.
      MAIN OUTCOME MEASURES: The Psoriasis Area and Severity Index (PASI) was used to
      assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary
      endpoint) and 13. Safety was assessed by monitoring all adverse events,
      laboratory investigations (blood chemistry, urinalysis, haematology) and physical
      examinations. RESULTS: The change from baseline in PASI at week 7 showed a dose
      dependent effect. The differences between each of the two higher doses of
      pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The
      mean percentage decreases from baseline in PASI in the placebo group and
      pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3%
      and 54.0%, respectively. Most adverse events were of mild or moderate severity.
      The only adverse event to show a dose-response relationship was a transient
      feeling of warmth. No clinically relevant effects on laboratory parameters were
      observed, and no increase in skin infection with pimecrolimus was seen.
      CONCLUSIONS: Oral pimecrolimus produces a dose-dependent reduction in psoriasis
      severity, with doses of 20 mg and 30 mg b.d. being the most effective and well
      tolerated.

PMID- 15948986
TI  - Air flow at different temperatures increases sodium lauryl sulphate-induced
      barrier disruption and irritation in vivo.
AB  - BACKGROUND: Combined exposure to dry climatic conditions and local heat sources
      together with detergents represents a common workplace situation. These
      conditions may support the induction of chronic barrier disruption leading
      subsequently to irritant contact dermatitis (ICD). OBJECTIVES: To test the
      irritant and barrier disrupting properties of air flow at different temperatures
      and velocities. METHODS: Using noninvasive biophysical measurements such as
      transepidermal water loss (TEWL) (TM 210; Courage & Khazaka, Cologne, Germany) we
      assessed the effects of short-term exposure to air flow at different temperatures
      (24 degrees C and 43 degrees C) in combination with sodium lauryl sulphate (SLS)
      0.5% on the skin of 20 healthy volunteers in a tandem repeated irritation test.
      Chromametry was used to control the accuracy of the SLS irritation model.
      RESULTS: In our study air flow alone did not lead to a significant increase in
      TEWL values. Sequential treatment with air flow and SLS led to an impairment of
      barrier function and irritation stronger than that produced by SLS alone. The two
      different air flow temperatures led to different skin temperatures but had no
      influence on permeability barrier function. CONCLUSIONS: Warm air flow has an
      additional effect on the SLS-induced barrier disruption in a tandem irritation
      test with sequential exposure to SLS/air flow. This combination is suspected to
      promote ICD in workplace and household situations, especially in short-term
      applications as tested in our model.

PMID- 15948987
TI  - Topical nanocrystalline silver cream suppresses inflammatory cytokines and
      induces apoptosis of inflammatory cells in a murine model of allergic contact
      dermatitis.
AB  - BACKGROUND: Nanocrystalline silver has both antimicrobial and anti-inflammatory
      properties. However, the exact mechanisms underlying these activities are not
      known. OBJECTIVES: The objectives of this study were to assess the anti
      inflammatory effects of nanocrystalline silver using a murine model of allergic
      contact dermatitis, compare the effects with those of tacrolimus and a high
      potency steroid, and to relate the effects to modulation of pro-inflammatory
      cytokines and apoptosis of inflammatory cells. METHODS: Dermatitis was induced on
      the ears of BALB/c mice using dinitrofluorobenzene. Topical treatment, including
      vehicles, 1% nanocrystalline silver cream, tacrolimus ointment and a high potency
      steroid, was applied once a day for 4 days. Ear swelling was measured and the
      erythema was evaluated daily. After 4 days of treatment the mice were killed and
      samples from the ears were collected for histological and immunohistochemical
      examination, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin
      nick end labelling (TUNEL) staining and extraction of total RNA for reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: Significant reductions
      of ear swelling, erythema and histopathological inflammation in mice ears were
      observed after 4 days of treatment with 1% nanocrystalline silver cream,
      tacrolimus ointment or a high potency steroid with no significant difference
      among them. Both RT-PCR and immunohistochemical staining of sections from ear
      biopsies demonstrated that nanocrystalline silver, tacrolimus and steroid
      significantly suppressed the expression of tumour necrosis factor (TNF)-alpha and
      interleukin (IL)-12. TUNEL staining demonstrated a significant increase in the
      numbers of apoptotic cells in material from the group treated with
      nanocrystalline silver when compared with that from groups treated with vehicle,
      tacrolimus or steroid. CONCLUSIONS: This study demonstrates that nanocrystalline
      silver inhibits allergic contact dermatitis in mice, similar to steroid and
      tacrolimus. Nanocrystalline silver suppresses the expression of TNF-alpha and IL
      12 and induces apoptosis of inflammatory cells; mechanisms by which
      nanocrystalline silver may exert its anti-inflammatory effects.

PMID- 15948988
TI  - Human papillomaviruses of the mucosal type are present in some cases of
      extragenital Bowen's disease.
AB  - BACKGROUND: Bowen's disease in the genital area is generally considered to be
      caused by mucosal high-risk human papillomaviruses (HPVs). However, the detection
      rate and spectrum of HPVs in extragenital Bowen's disease are various and it is
      not clear to what extent HPV is involved in its pathogenesis. OBJECTIVES: To
      assess the degree of association of HPV in extragenital cases by examining
      detection rates, types, quantities and localization of HPV. METHODS: A polymerase
      chain reaction (PCR) approach that we had previously established, which can give
      sensitive detection of a broad range of HPVs from cutaneous [including
      epidermodysplasia verruciformis-related HPVs (EV-HPVs)] to mucosal HPVs, was
      applied to samples from 41 patients with extragenital Bowen's disease and normal
      skin samples from 48 individuals. Semiquantitative L1-PCR and tyramide-based in
      situ hybridization (ISH) were also employed for positive cases. RESULTS: HPVs
      belonging to the mucosal high-risk group were detected in three patients with
      Bowen's disease (7%; two HPV 16 and one HPV 33), with 10(1)-10(3) copy
      equivalents per diploid amount of cellular DNA. They were distributed among most
      nuclei of tumour cells but in none of the cells of adjacent normal skin. HPVs
      belonging to the cutaneous group were detected in two patients (5%; HPV 27 and
      HPV 76) at 10(-2)-10(-3) copy equivalents, the same level as in a normal skin
      specimen positive for type 23 EV-HPV. No positive signals were observed by ISH.
      CONCLUSIONS: HPVs belonging to the mucosal high-risk group may participate in the
      development of extragenital Bowen's disease.

PMID- 15948989
TI  - Comparative analysis of the expression of ERBIN and Erb-B2 in normal human skin
      and cutaneous carcinomas.
AB  - BACKGROUND: ERBIN is a binding partner of Erb-B2, an orphan receptor within the
      Erb-B family critically involved in the regulation of cell growth and
      differentiation. Although its function remains unclear, ERBIN is thought to
      affect the polarity of epithelial cells and cell growth via the Ras signalling
      pathway. OBJECTIVES: To examine and compare the tissue distribution and the
      expression levels of ERBIN and Erb-B2 in normal skin and in cutaneous carcinomas.
      METHODS: Fifteen cases of basal cell carcinoma (BCC), 12 cases of squamous cell
      carcinoma (SCC) and five cases of keratoacanthoma (KA) were analysed by
      immunohistochemistry on paraffin-embedded sections using anti-ERBIN and anti-Erb
      B2 antibodies. RESULTS: ERBIN and Erb-B2 had a similar distribution in normal
      human skin. They were primarily localized at the plasma membrane in
      differentiated keratinocytes and in duct cells from eccrine glands, whereas they
      were localized diffusely in the cytoplasma of basal keratinocytes. In both SCC
      and KA the subcellular distribution of ERBIN and Erb-B2 remained unchanged,
      whereas both proteins were redistributed from the plasma membrane into cytosolic
      aggregates in BCC. CONCLUSIONS: The subcellular localization of ERBIN in normal
      human skin is similar to that of Erb-B2 and varies with cell differentiation.
      Based on our findings and on the biological activities of Erb-B2, it is
      conceivable that disturbed expression or functioning of ERBIN and Erb-B2 is
      implicated in the development of the malignant phenotype of BCC.

PMID- 15948990
TI  - Clinical management decisions are related to the impact of psoriasis on patient
      rated quality of life.
AB  - BACKGROUND: Clinical decisions over psoriasis are based on many factors.
      Patients' quality of life (QOL) is not directly related to disease severity alone
      as judged by physical signs, so decisions should not be based on physical
      assessments alone. This is increasingly important as new potent biological
      therapies become available. OBJECTIVES: This study aimed to determine whether
      clinicians' routine decisions in psoriasis correlate with patient-rated QOL.
      PATIENTS AND METHODS: Over 35 weeks all 687 outpatient psoriasis consultations by
      13 clinicians were included. Each patient received a Dermatology Life Quality
      Index (DLQI) questionnaire following their consultation. Case notes were analysed
      to assign management decisions taken by clinicians to one of 11 categories.
      Patient-rated DLQI was correlated with the type of management decision. RESULTS:
      Three hundred and eighty-three completed DLQI questionnaires were analysed.
      Within the 'no change to main type of therapy' group the mean DLQI for patients
      not changing the potency, dose or frequency of main treatment was 8.9. For
      patients in whom the potency, dose or frequency of main treatment was increased,
      the mean DLQI was 11.9. For patients in whom the potency, dose or frequency of
      main treatment was decreased, the mean DLQI was 6.2. Major management decisions
      were associated with a high mean DLQI such as change of topical therapy (11.2),
      topical to systemic therapy (14.8), change of systemic therapy (16.7), starting
      photo(chemo)therapy (13) and requiring hospital admission (14.4). By contrast,
      patients discharged reported low DLQI values (mean 4.0). The cohort of patients
      in whom a decision was taken to start day treatment had a surprisingly low mean
      DLQI of 8.6. Significant differences in mean DLQI were seen in the cohorts
      classified by type of management decision. For example, when the mean DLQI values
      in each cohort were compared (Mann-Whitney U-test), significant differences were
      seen between the cohorts in whom treatment was increased in potency, dose or
      frequency, compared with the cohorts whose treatment was unchanged (P < 0.05) or
      decreased (P < 0.01) or who were discharged from clinic (P < 0.01). CONCLUSIONS:
      In psoriasis there is a relationship between the type of management decision and
      the patient-rated QOL. However, there is a very wide score scatter for each
      management decision, challenging the appropriateness of some clinical decisions.

PMID- 15948991
TI  - In vitro evaluation of concurrent use of commercially available insect repellent
      and sunscreen preparations.
AB  - BACKGROUND: Insect repellents and sunscreens are over-the-counter products
      extensively used by the general public. Concurrent application of these products
      has become widespread in many regions across North America, because of concerns
      about West Nile virus and skin cancers. OBJECTIVES: We investigated whether
      formulation type, application amount, and sequence would affect the percutaneous
      absorption profiles of the active repellent and sunscreen ingredients. METHODS:
      In vitro percutaneous permeation of the repellent N,N-diethyl-m-toluamide (DEET)
      and the sunscreen oxybenzone from concurrent application of five commercially
      available products (A, repellent spray; B, repellent lotion; C, sunscreen lotion;
      D and E, combined repellent/sunscreen lotions) was measured and compared using
      Franz-style diffusion cells with piglet skin at 37 degrees C. RESULTS:
      Penetration of DEET in A and B increased by 1640% and 282%, respectively, when C
      was applied concurrently. Penetration of DEET in D and E was 53% and 79% higher
      than that in B. Permeation of DEET from A + C (2:1) and A + C (1: 2) increased by
      530% and 278%, respectively. Permeation of oxybenzone was 189% and 280% higher in
      A + C and B + C than in C. Permeation of oxybenzone in D and E was also 221% and
      296% higher than that in C. Permeation of oxybenzone was 196% greater when A was
      applied on top of C than when C was applied on top of A, while oxybenzone in A +
      C (1:2) permeated 171% more than that in A + C (2:1). CONCLUSIONS: Concurrent
      application of commercially available repellent and sunscreen products resulted
      in significant synergistic percutaneous permeation of the repellent DEET and the
      sunscreen oxybenzone in vitro. The percutaneous penetration profiles were
      dependent upon the type of formulation, application sequence and application
      proportion.

PMID- 15948992
TI  - Normalized ultraviolet (UV) induction of Langerhans cell depletion and neutrophil
      infiltrates after artificial UVB hardening of patients with polymorphic light
      eruption.
AB  - BACKGROUND: Ultraviolet (UV) B hardening has been widely used as a prophylactic
      treatment in patients with polymorphic light eruption (PLE). Recent
      investigations have shown that in patients with PLE Langerhans cells (LCs) and
      neutrophils display less migration from and to the epidermis after an intense UVB
      irradiation compared with controls. OBJECTIVES: To investigate the effect of UVB
      hardening of patients with PLE on their cell migratory responses after intense
      UVB exposure. METHODS: Thirteen patients with PLE were recruited and UVB
      provocation testing was performed before entering the study. Among these
      patients, seven developed PLE rash upon UVB provocation ('UVB-P') and the other
      six did not respond ('UVB-NP'). Eleven age/sex-matched controls were included.
      Buttock skin of all included individuals was exposed to 6 minimal erythema doses
      (MED) of UVB (TL-12 lamps). Biopsies were taken after 24 h and 48 h, together
      with one control biopsy of unirradiated skin. Patients received total-body UVB
      hardening therapy consisting of 12 irradiations, on average rising from 10% to
      140% of the initial MED in 6 weeks. Subsequently, MEDs were reassessed and
      biopsies were taken from newly irradiated (6 MED UVB) and unirradiated buttock
      skin. Skin sections were stained for the presence of LCs, macrophages and
      neutrophils. The cross-sectional area (in percentage) of positively stained cells
      within the epidermis was assessed from patients before and after hardening and
      compared with controls. RESULTS: Before therapy, epidermal LC depletion and
      neutrophil influx at 48 h after 6 MED were most significantly reduced in 'UVB-P'
      patients (P = 0.025 and P =0.006, respectively) when compared with controls. 'UVB
      NP' patients did not differ significantly from controls. After therapy, there
      were no longer any significant differences in the cell numbers among these three
      groups. CONCLUSIONS: UVB hardening significantly improves UV-induced cell
      migratory responses in patients with PLE. UVB provokability of PLE appears to be
      most strongly linked to reduced UVB-induced trafficking of LCs and neutrophils,
      and 'UVB-P' patients show normalization of these responses after UVB hardening.

PMID- 15948993
TI  - Common burden of chronic skin diseases? Contributors to psychological distress in
      adults with psoriasis and atopic dermatitis.
AB  - BACKGROUND: Chronic skin diseases, such as atopic dermatitis and psoriasis, are
      known to affect quality of life by heightening psychological distress. Knowledge
      about factors contributing to psychological distress is essential for supporting
      physicians in diagnostic and multidisciplinary treatment options for patients
      psychologically at risk. OBJECTIVES: To examine whether generic physical,
      psychological and social factors relevant to patients with chronic diseases might
      contribute to psychological distress in adults with psoriasis and atopic
      dermatitis. METHODS: Self-report data on clinical skin status, physical symptoms
      of itching and fatigue, impact of the disease on daily life, illness cognitions
      and social support were collected from 128 patients with psoriasis and 120
      patients with atopic dermatitis (aged over 16 years). RESULTS: For patients with
      either skin disease, clinical status and physical symptoms of itching scarcely
      affected psychological distress. Instead, higher levels of fatigue, perceived
      helplessness and less social support best predicted psychological distress in
      patients with both skin diseases in multiple regression analyses. CONCLUSIONS:
      Results demonstrate that generic physical, psychological and social aspects play
      a role in chronic skin diseases and suggest that multidisciplinary care for
      patients with psoriasis and atopic dermatitis can be greatly improved by
      integrating common screening and treatment components for chronic diseases.

PMID- 15948994
TI  - A multicentre, randomized, double-blind, controlled study of long-term treatment
      with 0.1% tacrolimus ointment in adults with moderate to severe atopic
      dermatitis.
AB  - BACKGROUND: Atopic dermatis (AD) is a chronic disease that often requires long
      term treatment. Topical corticosteroids are the usual therapy for patients with
      AD, but prolonged usage can result in skin atrophy and other side-effects.
      OBJECTIVES: In a randomized, double-blind, comparative study, to compare the
      efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment
      vs. a corticosteroid ointment regimen in adults with moderate to severe AD.
      METHODS: Treatment was applied twice daily for a maximum of 6 months. Patients in
      the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all
      affected areas over the whole body. The patients treated with the corticosteroid
      regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas
      on the trunk and extremities and 1% hydrocortisone acetate ointment to affected
      areas on the face and neck. The study primary endpoint was the response rate,
      i.e. the proportion of patients with at least 60% improvement in the modified
      Eczema Area and Severity Index (mEASI) between baseline and month 3. RESULTS: By
      month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6%
      vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1%
      tacrolimus also showed greater improvement in mEASI, EASI, affected body surface
      area and physician and patient assessments of global response. Patients applying
      0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the
      corticosteroid group; P < 0.001). In most patients, skin burning was mild to
      moderate in severity and decreased rapidly after the first week of treatment.
      There was no increase in the incidence of infections or malignancies over time in
      either treatment group. CONCLUSIONS: Long-term treatment with 0.1% tacrolimus
      ointment is significantly more efficacious than a corticosteroid ointment regimen
      in adults with moderate to severe AD.

PMID- 15948995
TI  - Therapy of noninfectious granulomatous skin diseases with fumaric acid esters.
AB  - BACKGROUND: Noninfectious granulomatous skin diseases are inflammatory disorders
      of unknown aetiology which are often recalcitrant to common anti-inflammatory
      treatment regimens. Recently, in several case reports, fumaric acid esters (FAE)
      have proved beneficial in granulomatous skin diseases, but studies on a larger
      collection of consecutive patients have not yet been performed. OBJECTIVES: To
      investigate the therapeutic efficacy of FAE for the treatment of granulomatous
      skin diseases. PATIENTS AND METHODS: The therapeutic efficacy and side-effects of
      FAE were analysed retrospectively in 32 patients with disseminated granuloma
      annulare (n = 13), annular elastolytic giant cell granuloma (n = 3), sarcoidosis
      (n = 11), necrobiosis lipoidica (n = 4), or granulomatous cheilitis (n = 1).
      RESULTS: Three patients discontinued treatment within 4 weeks because of side
      effects. Of the remaining 29 patients, 18 patients responded to treatment with
      FAE. Marked improvement or complete clearance was seen in seven patients. We
      observed a slight to moderate improvement in 11 patients, and 11 patients did not
      respond. In patients showing a complete remission, the maximum effect was
      observed after 8.5 months (SD +/-6 months, range 3-20 months). In two patients
      with systemic sarcoidosis, the pulmonary changes improved in parallel with the
      skin. Side-effects were usually mild and resolved spontaneously upon dose
      reduction or discontinuation of the therapy. CONCLUSIONS: The data presented here
      indicate that FAE may be considered for the treatment of recalcitrant
      granulomatous skin disease.

PMID- 15948996
TI  - Efficacy and tolerability of three different doses of oral pimecrolimus in the
      treatment of moderate to severe atopic dermatitis: a randomized controlled trial.
AB  - BACKGROUND: Adult atopic dermatitis (AD) can seriously affect quality of life of
      patients and their families, and patients' disease is frequently not
      satisfactorily controlled with topical therapy. There is a need for alternatives
      to topical treatment in patients with moderate to severe AD. OBJECTIVES: To
      investigate the efficacy and safety of oral pimecrolimus, and to determine the
      response to three different doses in the treatment of AD. METHODS: In a double
      blind, placebo-controlled, parallel-group, dose-finding study, patients with
      moderate to severe AD were randomized to receive either placebo, or oral
      pimecrolimus 10, 20 or 30 mg twice daily. The study consisted of a pretreatment
      phase, a 12-week double-blind treatment phase, and a 12-week post-treatment
      phase. RESULTS: In total, 103 patients were randomized. A clear, dose-dependent
      therapeutic effect of pimecrolimus treatment was observed, with a statistically
      significant onset of efficacy at week 2 and the greatest reduction from baseline
      of the Eczema Area and Severity Index of 66.6% at week 7 in the 30 mg twice daily
      dose group. Oral pimecrolimus was well tolerated and there were no signs of
      nephrotoxicity or the induction of hypertension. CONCLUSIONS: These data
      demonstrate the clinically relevant efficacy and short-term safety of oral
      pimecrolimus in adults with moderate to severe AD. Longer-term studies in larger
      cohorts are now required.

PMID- 15948997
TI  - A global phase III randomized controlled trial of etanercept in psoriasis:
      safety, efficacy, and effect of dose reduction.
AB  - BACKGROUND: In previous studies, etanercept significantly improved plaque
      psoriasis and was well tolerated. OBJECTIVES: To examine further the efficacy and
      safety of etanercept and to assess maintenance of treatment effect after dose
      reduction of etanercept. METHODS: In this multicentre 24-week study in the
      U.S.A., Canada and Western Europe, patients were at least 18 years old; had
      active, clinically stable plaque psoriasis involving at least 10% of body surface
      area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening;
      and had received or were a candidate to receive systemic psoriasis therapy or
      phototherapy. During the first 12 weeks of the study, patients were randomly
      assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a
      dose of 50 mg or 25 mg, or placebo BIW in a double-blind fashion. During the
      second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint
      was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks.
      RESULTS: Five hundred and eighty-three subjects were randomized and received at
      least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of
      patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in
      the placebo group (P < 0.0001 for each etanercept group compared with placebo).
      At week 24 (after 12 weeks of open-label 25 mg etanercept BIW), a PASI 75 was
      achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW,
      by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group
      that received placebo followed by etanercept 25 mg BIW. Etanercept was well
      tolerated throughout the study. CONCLUSIONS: Etanercept provided clinically
      meaningful benefit to patients with chronic plaque psoriasis, with no apparent
      decrease in efficacy after dose reduction.

PMID- 15948998
TI  - Functional MASP2 single nucleotide polymorphism plays no role in psoriasis.
AB  - BACKGROUND: Psoriasis is a heritable disease and genome-wide scans have
      implicated several loci of susceptibility. The gene for MASP-2, a protease
      involved in complement activation, is located within one of these loci on
      chromosome 1p. OBJECTIVES: To assess whether partial or total MASP-2 deficiency
      is a risk factor for developing psoriasis. METHODS: We screened a cohort of
      patients affected by plaque psoriasis and their parents by restriction fragment
      length polymorphism analyses. RESULTS: We detected a single nucleotide
      polymorphism that leads to an amino acid exchange, which results in dissociation
      of MASP-2 from a carbohydrate recognition complex. CONCLUSIONS: We show that this
      mutant allele is not associated with psoriasis. There was no favoured
      transmission from parents to affected offspring. The calculated allele frequency
      in this psoriasis group (Scottish and English) was 0.0326, and in the unaffected
      group 0.0379.

PMID- 15948999
TI  - The calcium-binding protein calretinin is a marker of the companion cell layer of
      the human hair follicle.
AB  - BACKGROUND: Ultrastructural studies of the hair follicle show that the outer root
      sheath (ORS) does not consist of a homogeneous cell population. The innermost
      cell layer of the ORS, also called the companion layer, is a single cell layer
      closely associated with the Henle layer of the inner root sheath. OBJECTIVES: To
      describe the immunohistochemical expression of calretinin, a calcium-binding
      protein, in the human hair follicle. METHODS: Immunohistochemical studies using
      two different antisera to calretinin were performed in paraffin-embedded and in
      frozen scalp specimens using standard techniques. RESULTS: Calretinin
      immunostaining was consistently and specifically found in the companion cell
      layer of hair follicles. CONCLUSIONS: These findings provide further evidence to
      support the notion that the companion layer is not only morphologically, but also
      immunohistochemically, different from the other cells of the ORS.

PMID- 15949000
TI  - Outcomes and pathological review of a cohort of children with melanoma.
AB  - BACKGROUND: Prepubertal malignant melanoma is rare, pathological criteria are
      difficult and follow-up data on patients are lacking in the literature.
      OBJECTIVES: To review prepubertal cases of melanoma diagnosed in the West of
      Scotland 1979-2002. METHODS: Twenty cases were identified in whom melanoma was
      diagnosed before the age of 15. Pathological review was possible for 13 of 20
      cases, and current follow-up information is available for all 20. Three
      pathologists not responsible for the original diagnosis reviewed the slides
      independently, in every case without knowledge of the outcome. RESULTS: Of the 13
      cases reviewed, there was concordance of diagnosis between the three pathologists
      in 12 cases. Eight of the 13 cases reviewed were considered to be unusual naevi
      rather than melanoma. One child has died of melanoma and all three pathologists
      agreed with the original pathological diagnosis. One patient has experienced
      nodal metastases but is alive and disease-free 12 years later. The remaining 18
      cases have had no recurrence since primary surgery 2-21 years ago. CONCLUSIONS:
      There may be a tendency to overdiagnose prepubertal melanoma. Good communication
      between clinician and pathologist and the use of an expert pathology panel is
      recommended before making the diagnosis.

PMID- 15949001
TI  - Comparison of dermoscopic and histopathological findings in a mucous melanoma of
      the lip.
AB  - Mucous melanomas on the lip are very rare. None of the few available reports has
      provided a comparison of dermoscopic and histopathological findings. We describe
      a 33-year-old Japanese man with a mucous melanoma on the lower lip and present a
      comparison of our dermoscopic and histopathological findings.

PMID- 15949002
TI  - Paraneoplastic pityriasis lichenoides in cutaneous lymphoma: case report and
      review of the literature on paraneoplastic reactions of the skin in lymphoma and
      leukaemia.
AB  - Paraneoplastic dermatoses are non-neoplastic skin disorders which occur in the
      context of an underlying malignant neoplasm. The classic paraneoplastic
      dermatoses are mostly associated with solid internal malignancies. They only
      rarely occur in the context of nodal or primary cutaneous lymphomas. Apart from
      these classic paraneoplastic dermatoses, there are additional skin disorders
      reported to occur in close association with haematological and
      lymphoproliferative disorders which can thus be regarded as paraneoplastic
      manifestations. We report for the first time two patients with pityriasis
      lichenoides et varioliformis acuta in association with mycosis fungoides. In
      addition, we review the literature on paraneoplastic dermatoses of the skin which
      have been described in patients with leukaemias and primary cutaneous lymphomas.

PMID- 15949003
TI  - Thalidomide in the management of epidermolysis bullosa pruriginosa.
AB  - Epidermolysis bullosa (EB) pruriginosa is a distinctive clinical subtype of
      dystrophic EB. We report a patient with dominant dystrophic EB pruriginosa, who
      had an excellent response to systemic thalidomide treatment. The mechanism of
      action of thalidomide in the management of pruriginous disorders is not yet
      completely understood. Most recent studies point towards an immunomodulatory
      action of thalidomide that may suppress excessive production of tumour necrosis
      factor-alpha and may downregulate certain cell surface adhesion molecules
      involved in leucocyte migration.

PMID- 15949004
TI  - Different phenotypes in Muir-Torre syndrome: clinical and biomolecular
      characterization in two Italian families.
AB  - The Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis
      characterized by the presence of sebaceous gland tumours, with or without
      keratoacanthomas, associated with visceral malignancies. We describe and
      characterize two families in which the ample phenotypic variability of MTS was
      evident. After clinical evaluation, the skin and visceral tumours of one member
      of a family with 'classic' MTS and one member of a family with a 'peculiar' MTS
      phenotype without sebaceous lesions, but with only multiple keratoacanthomas,
      were analysed for microsatellite instability (MSI) and by immunohistochemistry.
      Tumours of both individuals showed MSI, with a concomitant lack of MSH2
      immunostaining in all evaluated skin and visceral lesions; moreover, in the
      proband of family 2 a constitutional mutation (C-->T substitution leading to a
      stop codon) in the MSH2 gene was identified. We conclude that the diagnosis of
      MTS, which is mainly clinical, should take into account an ample phenotypic
      variability, which includes both cases with typical cancer aggregation in
      families and cases characterized by the association of visceral malignancies with
      multiple keratoacanthomas (without sebaceous lesions), without an apparent family
      history of cancer.

PMID- 15949005
TI  - Congenital brachydactyly and nail hypoplasia: clue to bone-dependent nail
      formation.
AB  - Congenital hyponychia and anonychia are rare malformations which may form part of
      syndromes such as nail-patella syndrome, ectodermal dysplasias and
      brachydactylies, or may occur as an isolated finding. Congenital hyponychia and
      anonychia are frequently accompanied by underlying skeletal abnormalities. A 20
      year-old woman showed congenital bilateral hypoplasia or aplasia of the second,
      third and fourth toenails with corresponding phalanx dysplasia or aplasia of the
      affected toes. Malformations of the hands or other congenital defects were
      absent. The findings in this patient do not exactly fit any known entities. Our
      clinical observation prompted us to review the literature on congenital
      hyponychia/anonychia and to summarize recent advances in understanding molecular
      events in nail development. In conclusion, the association of nail anomalies with
      aplasia and/or hypoplasia of corresponding middle and/or distal phalanges
      supports the hypothesis of bone-dependent nail formation.

PMID- 15949006
TI  - Extensive annular verrucous late secondary syphilis.
AB  - We report an illustrative case of an apparently healthy 38-year-old man with a
      past history of alopecia universalis who developed extensive, slightly pruritic,
      infiltrated annular verrucous lesions of the scalp, perioral, lumbar, perianal
      and genital areas over a 6-month period. The combination of an unusual clinical
      presentation, positive syphilis serology and rapid response to penicillin therapy
      was consistent with a diagnosis of extensive annular and verrucous late secondary
      syphilis. We present this case to illustrate a rare and potentially misleading
      clinical feature of late secondary syphilis, a disease considered to be of the
      past but still present in today's practice.

PMID- 15949007
TI  - Lymphomatoid papulosis in a patient with atopic eczema on long-term ciclosporin
      therapy.
AB  - We report a 36-year-old man with atopic eczema who developed lymphomatoid
      papulosis while taking ciclosporin. Latent membrane protein 1 and in situ
      hybridization for Epstein-Barr virus were negative. There are only two reports in
      the literature of patients taking ciclosporin to control atopic eczema who
      developed primary cutaneous CD30+ T-cell lymphoproliferative disorders. The
      development of T-cell lymphoproliferative disorders including lymphomas is well
      described in patients with solid organ transplants who are taking ciclosporin.
      Also, it has been noted in patients taking ciclosporin for rheumatological
      conditions or psoriasis.

PMID- 15949008
TI  - A successfully treated case of mycetoma due to Nocardia veterana.
AB  - We report a successfully treated case of mycetoma from which an unusual Nocardia
      species was isolated. The isolate was identified as N. veterana by biochemical
      characterization and 16S ribosomal RNA gene sequencing, and it has not been
      previously reported as a causative agent of human mycetomas. Treatment with
      various antibiotics over 6 years and surgical resection failed to cure the
      disease. However, the combination of intravenous imipenem/cilastatin and amikacin
      along with oral clarithromycin and minocycline proved very effective in this
      case. This is the first case report of mycetoma due to N. veterana in a clinical
      setting.

PMID- 15949009
TI  - Ichthyosis bullosa of Siemens: its correct diagnosis facilitated by molecular
      genetic testing.
AB  - Ichthyosis bullosa of Siemens (IBS, MIM 146800) is a unique congenital ichthyosis
      characterized by mild epidermal hyperkeratosis over flexural areas, blister
      formation and the development of superficially denuded areas of hyperkeratotic
      skin. It is clinically difficult to distinguish severe IBS from mild bullous
      congenital ichthyosiform erythroderma (BCIE, MIM 113800). In the current
      literature, 19 IBS families with keratin 2e (K2e) mutations have been reported,
      despite only five IBS families having been reported before the first
      identification of K2e mutation in 1994. We studied four patients from three
      Japanese IBS families. They had previously been misdiagnosed as having BCIE
      before the correct diagnosis was made after mutation detection. To detect the
      pathogenic mutations, we performed direct sequencing of the entire coding regions
      of KRT2E encoding K2e in the patients and healthy family members. K2e mutations,
      a 1469T-->C transition (L490P) and a 1477G-->A transition (E493K) within the
      conserved 2B helix termination motif of the rod domain were detected in the
      families and the definite diagnosis of IBS was made in the four cases. The
      present results indicate that IBS is not such a rare entity as was previously
      thought, and accurate diagnosis is now available by mutation analysis.

PMID- 15949011
TI  - Nicorandil-associated perianal ulceration with prominent elastophagocytosis and
      flexural ulceration.

PMID- 15949010
TI  - Two novel heterozygous mutations in COL7A1 in a Chinese patient with recessive
      dystrophic epidermolysis bullosa of Hallopeau-Siemens type.

PMID- 15949012
TI  - Human papillomavirus 60-positive epidermal cyst and wart at a nonpalmoplantar
      location.

PMID- 15949013
TI  - Tendency to underestimate the severity of androgenetic alopecia.

PMID- 15949015
TI  - Pimecrolimus 1% cream in the treatment of disseminated granuloma annulare.

PMID- 15949016
TI  - Lack of association of SPINK5 polymorphisms with nonsyndromic atopic dermatitis
      in the population of Northern Germany.

PMID- 15949017
TI  - No oncogenic mucosal human papillomaviruses in erosive vulval lichen planus.

PMID- 15949018
TI  - Low level laser: does it influence wound healing in venous leg ulcers? A
      randomized, placebo-controlled, double-blind study.

PMID- 15949019
TI  - Juvenile dermatomyositis in association with 22q11.2 deletion syndrome.

PMID- 15949020
TI  - Scleredema associated with carcinoma of the gall bladder.

PMID- 15949021
TI  - Unusual distribution of punctate dysplastic keratoses and skin cancers in sunbed
      users: a report of three cases.

PMID- 15949022
TI  - Wide-area 308-nm phototherapy with nonlaser light in the treatment of psoriasis:
      results of a pilot study.

PMID- 15949023
TI  - Is bone marrow biopsy necessary in patients with mycosis fungoides and Sezary
      syndrome? A histological and molecular study at diagnosis and during follow-up.

PMID- 15949024
TI  - Treatment of mycosis fungoides with bexarotene and psoralen plus ultraviolet A.

PMID- 15949025
TI  - Complicated mycosis fungoides mimicking facial erysipelas.

PMID- 15949026
TI  - Sclerotic and retracted supravenous hyperpigmentation associated with combination
      chemotherapy for metastatic breast carcinoma.

PMID- 15949027
TI  - Intravascular histiocytosis associated with rheumatoid arthritis: report of a
      case with lymphatic endothelial proliferation.

PMID- 15949028
TI  - Multiple dermoid cysts on the cheek.

PMID- 15949029
TI  - Common skin cancers in porokeratosis.

PMID- 15949030
TI  - Cre-loxP adenovirus-mediated foreign gene expression in skin-equivalent
      keratinocytes.

PMID- 15949031
TI  - Efficacy of issuing guidelines on acne management to general practitioners.

PMID- 15949032
TI  - Association between psoriasis and coeliac disease.

PMID- 15949033
TI  - Recovery of Mycobacterium tuberculosis DNA in biopsies of erythema induratum-
      results in a series of patients using an improved polymerase chain reaction
      technique.

PMID- 15949034
TI  - Empirical evaluation of prediction intervals for cancer incidence.
AB  - BACKGROUND: Prediction intervals can be calculated for predicting cancer
      incidence on the basis of a statistical model. These intervals include the
      uncertainty of the parameter estimates and variations in future rates but do not
      include the uncertainty of assumptions, such as continuation of current trends.
      In this study we evaluated whether prediction intervals are useful in practice.
      METHODS: Rates for the period 1993-97 were predicted from cancer incidence rates
      in the five Nordic countries for the period 1958-87. In a Poisson regression
      model, 95% prediction intervals were constructed for 200 combinations of 20
      cancer types for males and females in the five countries. The coverage level was
      calculated as the proportion of the prediction intervals that covered the
      observed number of cases in 1993-97. RESULTS: Overall, 52% (104/200) of the
      prediction intervals covered the observed numbers. When the prediction intervals
      were divided into quartiles according to the number of cases in the last observed
      period, the coverage level was inversely proportional to the frequency (84%, 52%,
      46% and 26%). The coverage level varied widely among the five countries, but the
      difference declined after adjustment for the number of cases in each country.
      CONCLUSION: The coverage level of prediction intervals strongly depended on the
      number of cases on which the predictions were based. As the sample size
      increased, uncertainty about the adequacy of the model dominated, and the
      coverage level fell far below 95%. Prediction intervals for cancer incidence must
      therefore be interpreted with caution.

PMID- 15949035
TI  - Overexpression of extracellular superoxide dismutase reduces acute radiation
      induced lung toxicity.
AB  - BACKGROUND: Acute RT-induced damage to the lung is characterized by inflammatory
      changes, which proceed to the development of fibrotic lesions in the late phase
      of injury. Ultimately, complete structural ablation will ensue, if the source of
      inflammatory/fibrogenic mediators and oxidative stress is not removed or
      attenuated. Therefore, the purpose of this study is to determine whether
      overexpression of extracellular superoxide dismutase (EC-SOD) in mice ameliorates
      acute radiation induced injury by inhibiting activation of TGFbeta1 and
      downregulating the Smad 3 arm of its signal transduction pathway. METHODS: Whole
      thorax radiation (single dose, 15 Gy) was delivered to EC-SOD overexpressing
      transgenic (XRT-TG) and wild-type (XRT-WT) animals. Mice were sacrificed at 1
      day, 1 week, 3, 6, 10 and 14 weeks. Breathing rates, right lung weights,
      total/differential leukocyte count, activated TGFbeta1 and components of its
      signal transduction pathway (Smad 3 and p-Smad 2/3) were assessed to determine
      lung injury. RESULTS: Irradiated wild-type (XRT-WT) animals exhibited time
      dependent increase in breathing rates and right lung weights, whereas these
      parameters were significantly less increased (p < 0.05) at 3, 6, 10 and 14 weeks
      in irradiated transgenic (XRT-TG) mice. An inflammatory response characterized
      predominantly by macrophage infiltration was pronounced in XRT-WT mice. This
      acute inflammation was significantly attenuated (p < 0.05) in XRT-TG animals at
      1, 3, 6 and 14 weeks. Expression of activated TGFbeta1 and components of its
      signal transduction pathway were significantly reduced (p < 0.05) at later time
      points in XRT-TG vs. XRT-WT. CONCLUSION: This study shows that overexpression of
      EC-SOD confers protection against RT-induced acute lung injury. EC-SOD appears to
      work, in part, via an attenuation of the macrophage response and also decreases
      TGFbeta1 activation with a subsequent downregulation of the profibrotic TGFbeta
      pathway.

PMID- 15949037
TI  - Correction: The effect of executive walk rounds on nurse safety climate
      attitudes: A randomized trial of clinical units [ISRCTN85147255].

PMID- 15949036
TI  - The therapeutic effect of the neuropeptide hormone somatostatin on Schistosoma
      mansoni caused liver fibrosis.
AB  - BACKGROUND: The neuropeptide somatostatin is one of the major regulatory peptides
      in the central nervous system and the digestive tract. Our recent work has
      delineated an association between fibrosis and low levels of endogenous
      somatostatin plasma levels in Schistosoma mansoni infected subjects. Based on
      these results this paper explores the therapeutic potential of somatostatin in a
      mouse model of hepatic fibrosis associated with S. mansoni infections. METHODS:
      Groups of outbred Swiss mice were infected with 100 S. mansoni cercariae,
      infection maintained till weeks 10 or 14, and then somatostatin therapy delivered
      in two regimens -- either a one or a two-day treatment. All animals were
      sacrificed one week after therapy and controlled for liver, spleen and total body
      weight. Circulating somatostatin levels in mice plasma were measured at the time
      of sacrifice by means of a radio-immuno assay. GraphPad Prism was used for
      statistical calculations. RESULTS: Somatostatin administration showed little
      toxicity, probably due to its short half-life. Total liver and spleen weights of
      S. mansoni infected animals increased over time, with no changes observed due to
      somatostatin therapy. Total body weights were decreased after infection but were
      not affected by somatostatin therapy. Snap frozen liver sections were stained
      with haematoxylin-eosin or Masson's trichrome to study parasite count, hepatocyte
      status, granuloma size and cellularity. After somatostatin treatment mean egg
      counts per liver section (43.76 +/- 3.56) were significantly reduced as compared
      to the egg counts in untreated mice after 10 weeks of infection (56.01 +/- 3.34)
      (P = 0.03). Similar significant reduction in parasite egg counts were also
      observed after somatostatin treatment at 14 weeks of infection (56.62 +/- 3.02)
      as compared to untreated animals (69.82 +/- 2.77)(P = 0.006). Fibrosis was
      assessed from the spectrophotometric determination of tissue hydroxyproline.
      Infection with S. mansoni caused increased hydroxyproline levels (9.37 +/- 0.63
      micromol at wk 10; 9.65 +/- 0.96 micromol at wk 14) as compared to uninfected
      animals (1.06 +/- 0.10 micromol). This significant increase in collagen content
      (P = 0.01; 0.007 respectively) marks the fibrosis observed at these time points.
      Treatment with somatostatin resulted in a significant decrease in hydroxyproline
      levels both at wk 10 (4.76 +/- 0.58 micromol) and at wk 14 (5.8 +/- 1.13
      micromol) (P = 0.01; 0.03 respectively). Endogenous somatostatin levels were
      increased at wk 10 (297 +/- 37.24 pg/ml) and wk 14 (206 +/- 13.30 pg/ml) of
      infection as compared to uninfected mice (119 +/- 11.99 pg/ml) (P = 0.01; 0.008
      respectively). Circulating somatostatin levels in infected animals were not
      significantly affected by somatostatin treatment. Hepatocyte status remained
      unaltered and granulomas were not remarkably changed in size or cellularity.
      CONCLUSION: Our experiments reveal an antifibrotic effect of somatostatin in
      schistosomiasis. We have previously shown that the somatostatin receptors SSTR2
      and SSTR3 are present on the parasite egg and worms. We therefore hypothesize
      that somatostatin reduces either the number of parasite eggs or the secretion of
      fibrosis inducing-mediators. Our data suggest somatostatin may have therapeutic
      potential in S. mansoni mediated liver pathology.

PMID- 15949038
TI  - Inferring yeast cell cycle regulators and interactions using transcription factor
      activities.
AB  - BACKGROUND: Since transcription factors are often regulated at the post
      transcriptional level, their activities, rather than expression levels may
      provide valuable information for investigating functions and their interactions.
      The recently developed Network Component Analysis (NCA) and its generalized form
      (gNCA) provide a robust framework for deducing the transcription factor
      activities (TFAs) from various types of DNA microarray data and transcription
      factor-gene connectivity. The goal of this work is to demonstrate the utility of
      TFAs in inferring transcription factor functions and interactions in
      Saccharomyces cerevisiae cell cycle regulation. RESULTS: Using gNCA, we
      determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray
      data encompassing 1529 ORFs. We hypothesized that transcription factors
      participating in the cell cycle regulation exhibit cyclic activity profiles. This
      hypothesis was supported by the TFA profiles of known cell cycle factors and was
      used as a basis to uncover other potential cell cycle factors. By combining the
      results from both cluster analysis and periodicity analysis, we recovered nearly
      90% of the known cell cycle regulators, and identified 5 putative cell cycle
      related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1). In addition,
      by analyzing expression data from transcription factor knockout strains, we
      determined 3 verified (Ace2, Ndd1, and Swi5) and 4 putative interaction partners
      (Cha4, Hap2, Fhl1, and Rts2) of the forkhead transcription factors. Sensitivity
      of TFAs to connectivity errors was determined to provide confidence level of
      these predictions. CONCLUSION: By subjecting TFA profiles to analyses based upon
      physiological signatures we were able to identify cell cycle related
      transcription factors consistent with current literature, transcription factors
      with potential cell cycle dependent roles, and interactions between transcription
      factors.

PMID- 15949039
TI  - Does cholesterol act as a protector of cholinergic projections in Alzheimer's
      disease?
AB  - The relationship between Alzheimer's disease (AD) and progressive degeneration of
      the forebrain cholinergic system is very well established, whereas mechanisms
      linking this disease with cholesterol, apolipoprotein E (apoE) phenotype, and
      amyloid precursor protein (APP) metabolism have not been fully elucidated even
      though there is a plethora of publications separately on each of these issues.
      The intention of this hypothesis is to unify knowledge coming from all of these
      areas. It is based on an assumption that the process of APP hypermetabolism is a
      neuroprotective response for age-related cholinergic deterioration. In some
      individuals this initially positive process becomes highly overregulated by
      genetic or/and epigenetic risk factors and after many years of accumulations lead
      eventually to AD. I hypothesise that neuroprotective role of APP-hypermetabolism
      might be related to enrichment of neuronal membranes (lipid rafts in particular)
      in cholesterol in order to compensate for decrease in presynaptic cholinergic
      transmission and/or AD-related decrease in cholesterol levels. The above is
      consistent with findings indicating that activity of both muscarinic and
      nicotinic cholinergic receptors is correlated in a positive manner with
      cholesterol plasmalemmal content. Briefly--APP metabolism together with transport
      of cholesterol in apoE containing lipoproteins seem to play a key role in
      mobilising cholesterol into neuronal membranes.

PMID- 15949040
TI  - HIV-1 Rev oligomerization is not obligatory in the presence of an extra basic
      domain.
AB  - BACKGROUND: The HIV-1 Rev regulatory protein binds as an oligomeric complex to
      viral RNA mediating nuclear export of incompletely spliced and non-spliced viral
      mRNAs encoding the viral structural proteins. However, the biological
      significance of the obligatory complex formation of Rev upon the viral RNA is
      unclear. RESULTS: The activity of various fusion proteins based on the negative
      oligomerization-defect Rev mutant M4 was tested using Rev dependent reporter
      constructs. An artificial M4 mutant dimer and an M4 mutant containing an extra
      basic domain from the HTLV-I Rex protein exhibited nearly full activity when
      compared to wild type Rev. CONCLUSION: Rev dimerization appears to be required to
      expose free basic domains whilst the Rev oligomeric complex remains bound to
      viral RNA via other basic domains.

PMID- 15949041
TI  - Toe spreading ability in men with chronic pelvic pain syndrome.
AB  - BACKGROUND: We examined toe-spreading ability in subjects with chronic pelvic
      pain syndrome (CPPS) to test the hypothesis that subjects with CPPS could have
      deficiencies in lower extremity functions innervated by sacral spinal roots.
      METHODS: Seventy two subjects with CPPS and 98 volunteer controls were examined
      as part of a larger study on CPPS. All the subjects underwent a detailed urologic
      and neurological examination including a toe-spreading examination with a
      quantitative scoring system. We compared the groups in terms of ability of toe
      spreading as either "complete" (all toes spreading) or "incomplete" (at least one
      interdigital space not spreading) and also by comparing the number of
      interdigital spaces. For CPPS subjects only, we also analyzed the variation of
      the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI)
      scales by toe-spreading categories. RESULTS: CPPS subjects were less often able
      to spread all toes than subjects without CPPS (p = 0.005). None of the NIH-CPSI
      sub-scales (pain, urinary symptoms, and quality of life), nor the total score
      showed an association with toe spreading ability. CONCLUSION: We found toe
      spreading to be diminished in subjects with CPPS. We hypothesize that incomplete
      toe spreading in subjects with CPPS may be related to subtle deficits involving
      the most caudal part of the spinal segments.

PMID- 15949043
TI  - Effect of pre-stroke use of ACE inhibitors on ischemic stroke severity.
AB  - BACKGROUND: Recent trials suggest that angiotensin-converting enzyme inhibitors
      (ACEI) are effective in prevention of ischemic stroke, as measured by reduced
      stroke incidence. We aimed to compare stroke severity between stroke patients who
      were taking ACEI before their stroke onset and those who were not, to examine the
      effects of pretreatment with ACEI on ischemic stroke severity. METHODS: We
      retrospectively studied 126 consecutive patients presenting within 24 hours of
      ischemic stroke onset, as confirmed by diffusion-weighted magnetic resonance
      imaging (DWI). We calculated the NIHSS score at presentation, as the primary
      measure of clinical stroke severity, and categorized stroke severity as mild
      (NIHSS [less than or equal to] 7), moderate (NIHSS 8-13) or severe (NIHSS
      [greater than or equal to] 14). We analyzed demographic data, risk-factor
      profile, blood pressure (BP) and medications on admissions, and determined stroke
      mechanism according to TOAST criteria. We also measured the volumes of admission
      diffusion- and perfusion-weighted (DWI /PWI) magnetic resonance imaging lesions,
      as a secondary measure of ischemic tissue volume. We compared these variables
      among patients on ACEI and those who were not. RESULTS: Thirty- three patients
      (26%) were on ACE-inhibitors. The overall median baseline NIHSS score was 5.5
      (range 2-21) among ACEI-treated patients vs. 9 (range 1-36) in non-ACEI patients
      (p = 0.036). Patients on ACEI prior to their stroke had more mild and less severe
      strokes, and smaller DWI and PWI lesion volumes compared to non-ACEI treated
      patients. However, none of these differences were significant. Predictably, a
      higher percentage of patients on ACEI had a history of heart failure (p = 0.03).
      Age, time-to-imaging or neurological evaluation, risk-factor profile, concomitant
      therapy with lipid lowering, other antihypertensives or antithrombotic agents, or
      admission BP were comparable between the two groups. CONCLUSION: Our results
      suggest that ACE-inhibitors may reduce the clinical severity of stroke, as
      measured by NIHSS score. Further, larger-scale, prospective studies are needed to
      validate our findings, and to elucidate the mechanism(s) of ACEImediated benefits
      in patients with ischemic stroke.

PMID- 15949044
TI  - Satellog: a database for the identification and prioritization of satellite
      repeats in disease association studies.
AB  - BACKGROUND: To date, 35 human diseases, some of which also exhibit anticipation,
      have been associated with unstable repeats. Anticipation has been reported in a
      number of diseases in which repeat expansion may have a role in etiology. Despite
      the growing importance of unstable repeats in disease, currently no resource
      exists for the prioritization of repeats. Here we present Satellog, a database
      that catalogs all pure 1-16 repeat unit satellite repeats in the human genome
      along with supplementary data. Satellog analyzes each pure repeat in UniGene
      clusters for evidence of repeat polymorphism. RESULTS: A total of 5,546 such
      repeats were identified, providing the first indication of many novel polymorphic
      sites in the genome. Overall, polymorphic repeats were over-represented within 3'
      UTR sequence relative to 5'-UTR and coding sequence. Interestingly, we observed
      that repeat polymorphism within coding sequence is restricted to trinucleotide
      repeats whereas UTR sequence tolerated a wider range of repeat period
      polymorphisms. For each pure repeat we also calculate its repeat length
      percentile rank, its location either within or adjacent to EnsEMBL genes, and its
      expression profile in normal tissues according to the GeneNote database.
      CONCLUSION: Satellog provides the ability to dynamically prioritize repeats based
      on any of their characteristics (i.e. repeat unit, class, period, length, repeat
      length percentile rank, genomic co-ordinates), polymorphism profile within
      UniGene, proximity to or presence within gene regions (i.e. cds, UTR, 15 kb
      upstream etc.), metadata of the genes they are detected within and gene
      expression profiles within normal human tissues. Unstable repeats associated with
      31 diseases were analyzed in Satellog to evaluate their common repeat properties.
      The utility of Satellog was highlighted by prioritizing repeats for Huntington's
      disease and schizophrenia. Satellog is available online at
      http://satellog.bcgsc.ca.

PMID- 15949042
TI  - Expression of human AID in yeast induces mutations in context similar to the
      context of somatic hypermutation at G-C pairs in immunoglobulin genes.
AB  - BACKGROUND: Antibody genes are diversified by somatic hypermutation (SHM), gene
      conversion and class-switch recombination. All three processes are initiated by
      the activation-induced deaminase (AID). According to a DNA deamination model of
      SHM, AID converts cytosine to uracil in DNA sequences. The initial deamination of
      cytosine leads to mutation and recombination in pathways involving replication,
      DNA mismatch repair and possibly base excision repair. The DNA sequence context
      of mutation hotspots at G-C pairs during SHM is DGYW/WRCH (G-C is a hotspot
      position, R = A/G, Y = T/C, W = A/T, D = A/G/T). RESULTS: To investigate the
      mechanisms of AID-induced mutagenesis in a model system, we studied the genetic
      consequences of AID expression in yeast. We constructed a yeast vector with an
      artificially synthesized human AID gene insert using codons common to highly
      expressed yeast genes. We found that expression of the artificial hAIDSc gene was
      moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil
      DNA glycosylase-deficient strain. A majority of mutations were at G-C pairs. In
      the ung1 strain, C-G to T-A transitions were found almost exclusively, while a
      mixture of transitions with 12% transversions was characteristic in the wild-type
      strain. In the ung1 strain mutations that could have originated from deamination
      of the transcribed stand were found more frequently. In the wild-type strain, the
      strand bias was reversed. DGYW/WRCH motifs were preferential sites of mutations.
      CONCLUSION: The results are consistent with the hypothesis that AID-mediated
      deamination of DNA is a major cause of mutations at G-C base pairs in
      immunoglobulin genes during SHM. The sequence contexts of mutations in yeast
      induced by AID and those of somatic mutations at G-C pairs in immunoglobulin
      genes are significantly similar. This indicates that the intrinsic substrate
      specificity of AID itself is a primary determinant of mutational hotspots at G-C
      base pairs during SHM.

PMID- 15949045
TI  - Determination of caspase-3 activation fails to predict chemosensitivity in
      primary acute myeloid leukemia blasts.
AB  - BACKGROUND: Ex-vivo chemosensitivity tests that measure cell death induction may
      predict treatment outcome and, therefore, represent a powerful instrument for
      clinical decision making in cancer therapy. Such tests are, however, work
      intensive and, in the case of the DiSC-assay, require at least four days.
      Induction of apoptosis is the mode of action of anticancer drugs and should,
      therefore, result in the induction of caspase activation in cells targeted by
      anticancer therapy. METHODS: To determine, whether caspase activation can predict
      the chemosensitivity, we investigated enzyme activation of caspase-3, a key
      executioner caspase and correlated these data with chemosensitivity profiles of
      acute myeloid leukemia (AML) blasts. RESULTS: There was, however, no correlation
      between the ex-vivo chemosensitivity assessed by measuring the overall rates of
      cell death by use of the DiSC-assay and caspase-3 activation. CONCLUSION: Thus,
      despite a significant reduction of duration of the assay from four to one day,
      induction of apoptosis evaluated by caspase-3 activity does not seem to be a
      valid surrogate marker for chemosensitivity.

PMID- 15949046
TI  - A new journal - "Theoretical Biology and Medical Modelling".
AB  - Biology has a conceptual basis that allows one to build models and theorize
      across many life sciences, including medicine and medically-related disciplines.
      A dearth of good venues for publication has been perceived during a period when
      bioinformatics, systems analysis and biomathematics are burgeoning. Steps have
      been taken to provide the sort of journal with a quick turnaround time for
      manuscripts which is online and freely accessible to all readers, whatever their
      persuasion or discipline. We have now been running for some time a journal which
      has had many good papers presented pre-launch, and a steady stream of papers
      thereafter. The value of this journal as a new venue has already been vindicated.
      Within a short space of time, we have founded a state-of-the-art electronic
      journal freely accessible to all in a much sort-after interdisciplinary field
      that will be of benefit to the thinking life scientist, which must include
      medically qualified doctors as well as scientists who prefer to build their new
      hypotheses on basic principles and sound concepts underpinning biology. At the
      same time, these principles are not sacrosanct and require critical analysis. The
      journal http://www.tbiomed.com promises to deliver many exciting ideas in the
      future.

PMID- 15949047
TI  - Phase II trial of weekly 24-hour infusion of gemcitabine in patients with
      advanced gallbladder and biliary tract carcinoma.
AB  - BACKGROUND: Patients with advanced gallbladder and biliary tract carcinoma face a
      dismal prognosis, as no effective palliative chemotherapy exists. The antitumor
      effect of gemcitabine is schedule-dependent rather than dose-dependent. We
      evaluated the activity of a prolonged infusion of gemcitabine in advanced
      gallbladder and biliary tract carcinomas. METHODS: Nineteen consecutive eligible
      patients were enrolled. All patients were required to have histologically
      confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours
      at a dose of 100 mg/m2 on days 1, 8, and 15. Treatment was repeated every 28 days
      until progression of disease or limiting toxicity. Tumor response was evaluated
      every second course by computed tomography (CT) scans. RESULTS: Eighteen patients
      were evaluable for response. A total of 89 cycles of therapy were administered.
      One partial response was observed (6%; 95% confidence interval (CI): 0-27%) and
      ten additional patients had stable disease for at least two months (disease
      control rate 61%; 95% CI: 36-83%). The therapy was well tolerated, with moderate
      myelosuppression as the main toxicity. The median time to tumor progression and
      median overall survival was 3.6 months (95% CI 2.6-4.6 months) and 7.5 months
      (95% CI 6.5-8.5 months), respectively. CONCLUSION: Weekly 24-hour gemcitabine at
      a dose of 100 mg/m2 is well tolerated. There was a relatively high rate of
      disease control for a median duration of 5.3 months (range 2.8-18.8 months).
      However, the objective response rate of this regimen in gallbladder and biliary
      tract carcinomas was limited.

PMID- 15949048
TI  - Identification and mapping of yield and yield related QTLs from an Indian
      accession of Oryza rufipogon.
AB  - BACKGROUND: Cultivated rice (Oryza sativa L.) is endowed with a rich genetic
      variability. In spite of such a great diversity, the modern rice cultivars have
      narrow genetic base for most of the agronomically important traits. To sustain
      the demand of an ever increasing population, new avenues have to be explored to
      increase the yield of rice. Wild progenitor species present potential donor
      sources for complex traits such as yield and would help to realize the dream of
      sustained food security. RESULTS: Advanced backcross method was used to
      introgress and map new quantitative trait loci (QTLs) relating to yield and its
      components from an Indian accession of Oryza rufipogon. An interspecific BC2
      testcross progeny (IR58025A/O. rufipogon//IR580325B///IR58025B////KMR3) was
      evaluated for 13 agronomic traits pertaining to yield and its components.
      Transgressive segregants were obtained for all the traits. Thirty nine QTLs were
      identified using interval mapping and composite interval mapping. In spite of
      it's inferiority for most of the traits studied, O. rufipogon alleles contributed
      positively to 74% of the QTLs. Thirty QTLs had corresponding occurrences with the
      QTLs reported earlier, indicating that these QTLs are stable across genetic
      backgrounds. Nine QTLs are novel and reported for the first time. CONCLUSION: The
      study confirms that the progenitor species constitute a prominent source of still
      unfolded variability for traits of complex inheritance like yield. With the
      availability of the complete genome sequence of rice and the developments in the
      field of genomics, it is now possible to identify the genes underlying the QTLs.
      The identification of the genes constituting QTLs would help us to understand the
      molecular mechanisms behind the action of QTLs.

PMID- 15949049
TI  - Treatment of abdominal aortic aneurysms with an endovascular stent-graft
      prosthesis in 96 high-risk patients.
AB  - . Ninety-six patients, mean age 72 +/- 8 years, with an abdominal aortic aneurysm
      (AAA) and significant comorbidities with a vascular anatomy favorable for
      supporting an endovascular prosthesis underwent endovascular repair of the AAA.
      The 90-day survival was 100%. The incidence of endoleaks at 25-month mean follow
      up was 4 of 96 patients (4%). None of the 96 patients (0%) required surgical
      conversion of the AAA. At 14-month mean follow up after endovascular repair, the
      diameter of the AAA was significantly reduced from 6.2 +/- 1.2 cm to 5.0 +/- 1.1
      cm (P < 0.001).

PMID- 15949050
TI  - Chest pain from gastroesophageal reflux disease in patients with coronary artery
      disease.
AB  - Management of patients with coronary artery disease is a major challenge for
      physicians, patients, and the healthcare system. Chest pain experienced by
      patients with coronary disease can be of noncardiac origin, and symptoms
      frequently related to gastroesophageal etiologies. The distal esophagus and the
      heart share a common afferent nerve supply, suggesting that location and
      radiation of perceived pain may be identical. In addition, there is substantial
      overlap between the prevalence of coronary disease and gastroesophageal reflux
      disease. Many physicians, including cardiologists, prescribe acid-reducing
      therapy to coronary patients. However, no prospective, randomized studies to date
      have evaluated the potential benefit of such treatments to prevent chest pain
      symptoms for these patients. We review the studies on noncardiac chest pain
      demonstrating reflux in patients with and without coronary disease. Also, the
      association of reflux with exertional chest pain and cardiac syndrome X is
      discussed. A rationale is presented for prevention of noncardiac chest pain in
      coronary patients, and the potential role of acid-suppressive therapy in managing
      these patients is discussed.

PMID- 15949051
TI  - Electron beam tomography in women. Is it a valuable test?
AB  - Cardiovascular disease (CVD) is the leading cause of mortality in women and a
      major cause of morbidity. Coronary artery disease (CAD) accounts for nearly half
      of all CVD deaths. Traditional risk factors are very helpful in predicting the
      development of CAD in women; however, many women suffer events in the absence of
      established risk factors for atherosclerosis. To meet the challenge of CAD,
      several tools have been developed to identify atherosclerotic disease in its
      preclinical stages, with the hope of modifying its natural history. In this
      article, we review the current literature on utilization of electron beam
      tomography (EBT) for detection of CAD as a tool to conduct risk stratification in
      the general asymptomatic female population as well as among asymptomatic women.
      In conclusion, EBT can be used to estimate the overall coronary atherosclerotic
      plaque burden in women. It can also be used to diagnose its presence and
      determine its extent; furthermore, information from the coronary artery calcium
      scores can be used to assess the likelihood of obstructive disease and to provide
      prognostic information. Finally, EBT has the potential to determine the
      consequences of therapeutic interventions regarding progression, stabilization,
      or regression of coronary atherosclerotic disease.

PMID- 15949052
TI  - Coronary revascularization in women.
AB  - Coronary revascularization procedures have less salutary outcomes for women than
      for their male peers. Procedural bleeding complications, among others, warrant
      pathophysiologic assessment; limitation of such complications can improve
      clinical outcomes for women.

PMID- 15949053
TI  - A history of orthotopic heart transplantation.
AB  - Orthotopic human heart transplantation today is performed at more than 150 U.S.
      centers, and the average survival is more than 10 years. Its prevalence and
      success, however, belies the fact that just 40 years ago, no one had ever
      attempted the procedure in humans and that the procedure seemed destined for
      failure just a year after the first transplant. This article reviews the history
      of orthotopic heart transplantation, beginning with ancient Greek legends and
      culminating in modern successes.

PMID- 15949054
TI  - Nonsurgical carotid revascularization.
AB  - Carotid endarterectomy is a well-established treatment of improving the carotid
      luminal diameter and preventing strokes, and the indications and complications
      are well-defined. Carotid angioplasty and stent placements are relatively newer
      ways of treating carotid artery stenosis. In certain contexts, they may have some
      advantages over carotid endarterectomy. However, the success rates, morbidity,
      and mortality associated with these procedures are less well characterized. In
      earlier comparative studies, the incidence of ipsilateral stroke rate was higher
      with angioplasty, but in later studies, this trend is reversing. Angioplasty may
      also have an edge in specific situations like patients with coexisting
      significant coronary arterial disease, contralateral carotid artery occlusion,
      and in instances when the narrowing is long and at multiple sites. Protective
      devices like distal occlusion balloon and filter protection devices may reduce
      the incidence of stroke. We are still awaiting the results of some major
      randomized head-to-head trials comparing carotid endarterectomy and stenting.

PMID- 15949055
TI  - Spiral coronary dissection after percutaneous coronary intervention with
      retrograde propagation into the ascending aorta.

PMID- 15949056
TI  - Ranolazine. A metabolic modulator for the treatment of chronic stable angina.
AB  - Ranolazine is a novel new antianginal agent currently under investigation as
      monotherapy and adjunct therapy for the treatment of chronic stable angina. While
      the mechanism of action of ranolazine is not completely understood, it is
      believed to involve a reduction in fatty acid oxidation, ultimately leading to a
      shift in myocardial energy production from fatty acid oxidation to glucose
      oxidation. Since the oxidation of glucose requires less oxygen than the oxidation
      of fatty acids, ranolazine can help maintain myocardial function in times of
      ischemia. In addition, ranolazine has minimal effect on blood pressure and heart
      rate. Ranolazine, by inhibiting cellular ionic channels, prolongs the corrected
      QT interval. However, ranolazine has not yet been associated with any incidences
      of ventricular arrhythmia. The clinical data with ranolazine focuses on its use
      in chronic stable angina, where it has been shown to increase exercise tolerance
      and decrease angina compared with placebo, as well as in combination with beta
      blockers and calcium channel blockers. The use of ranolazine for other cardiac
      conditions and the effect of ranolazine on morbidity and mortality remains to be
      determined. Ongoing clinical trials will help further establish the role of
      ranolazine in the treatment of cardiovascular disorders.

PMID- 15949057
TI  - Spontaneous coronary artery dissection as a cause of acute myocardial infarction
      in the postpartum period.
AB  - Spontaneous coronary dissection is an infrequent cause of acute myocardial
      infarction, and several cases have been presented during the peripartum period.
      We present a case of acute myocardial infarction resulting from spontaneous
      coronary artery dissection, in a 37-year-old woman during the postpartum period.
      Thrombolytic treatment was administered in the emergency room uneventfully but
      without symptom resolution. Diagnosis was subsequently established by coronary
      arteriography. The patient's in-hospital and long-term clinical course and
      prognosis are described and the potential pathogenetic mechanisms are discussed.
      Finally, the treatment options for this rare entity are presented.

PMID- 15949058
TI  - Left ventricular cardiac tamponade in the setting of cor pulmonale and
      circumferential pericardial effusion. Case report and review of the literature.
AB  - Circumferential pericardial effusion typically results in biventricular tamponade
      and equalization of intracardiac and pericardial pressure during diastole.
      However, tamponade may involve the right or left ventricle. While isolated left
      ventricular cardiac tamponade (LVCT) can occur as a postoperative complication
      from localized posterior pericardial effusions, circumferential pericardial
      effusions leading to LVCT are rare. We report a case of a patient with severe
      pulmonary hypertension, a large nonloculated pericardial effusion, and LVCT,
      which was probably due to a chronic undifferentiated connective tissue disorder.
      This case illustrates that when evaluating patients with circumferential
      pericardial effusions and associated pulmonary hypertension, the typical findings
      of cardiac tamponade (pulsus paradoxus, right ventricular diastolic compression
      and hypotension) may be masked. The echocardiogram must be reviewed carefully as
      it may reveal left ventricular diastolic compression, the hallmark of LVCT, which
      may significantly compromise left ventricular filling and cardiac output.

PMID- 15949060
TI  - Efficacy of interventions in improving adherence to antiretroviral therapy.
AB  - The aim of this paper is to perform a critical review of the effectiveness of
      interventions for the purpose of enhancing adherence to antiretroviral therapy.
      The overall evaluation indicates that research is in its early stages. Although
      pilot studies provide support for the feasibility of their protocols, and
      preliminary results also suggest their capacity to improve adherence, only three
      major trials have reported significant improvement in adherence. The issues that
      will have to be addressed by future studies include: (a) the need for a
      theoretical and empirical understanding of the phenomena; (b) adoption of a
      format that fits the attributes of the population; (c) the use of multiple
      strategies involving key providers; (d) a concise and precise schedule governing
      the frequency and intensity of the intervention; (e) a careful selection of
      direct outcome; and (f) appropriate time measurement. In sum, greater efforts to
      design and evaluate interventions are needed to lead to an increase in adherence
      and improvement in treatment effectiveness.

PMID- 15949059
TI  - Effects of acupuncture at GV01 on experimentally induced colitis in rats:
      possible involvement of the opioid system.
AB  - Oriental medicine uses acupuncture at the GV01 acupoint with great success to
      treat diarrhea. It significantly reduced the colonic motility and inflammation in
      colitic rats. Naloxone pretreatment blocked these effects. The therapeutic
      effects of acupuncture at GV01 in colitis may involve endogenous opioid pathways.

PMID- 15949062
TI  - Incorrect condom use and frequent breakage among female sex workers and their
      clients.
AB  - Our objective was to assess if female sex workers (FSWs) and their potential male
      clients in Cotonou, Benin, know how to use male condoms correctly. From April to
      June 2000, 314 FSWs and 208 men were interviewed, and asked to demonstrate on a
      wooden penis how they usually use male condoms. In all, 27.6% of both women and
      men tore the condom envelope on the notch; 89.3% of the women versus 75.4% of the
      men easily found the correct side; 17.3% of the women versus 28.3% of the men
      held the top of the condom to avoid air entering; 91.4% of the women versus 75.6%
      of the men correctly unrolled the condom. Taking all the four criteria together,
      only approximately 11% of participants performed a correct condom use
      demonstration. FSWs frequently reported condom breakage, which was significantly
      associated with incorrect condom demonstration (P = 0.04). Correct condom use is
      suboptimal in these heavy consumers of male condoms in Benin. Condom breakage is
      frequent and is associated with incorrect use.

PMID- 15949063
TI  - Screening, diagnosis and management of early syphilis in genitourinary medicine
      clinics in the UK.
AB  - New diagnoses of syphilis in the UK increased eight-fold between 1997 and 2002.
      This study, conducted in 2002, demonstrated that 31% of clinics were not
      confident of their expertise to obtain an adequate specimen for dark ground
      microscopy (DGM), and 35% were not confident of their expertise to detect
      treponemes on DGM. In all, 64% of clinics had observed adherence problems in HIV
      positive patients treated with parenteral regimens, as against 42% with oral
      regimens. Also, 51% of clinics waited more than a week for the results of initial
      serological tests for syphilis, and 88% of clinics waited more than a week for
      confirmatory test results. Other concerns include the failure to perform syphilis
      serology consistently whenever HIV-positive patients were at risk, and the
      widespread use of doxycycline as a therapy for syphilis in HIV-positive patients
      despite concerns that this is not known to be fully treponemicidal in
      cerebrospinal fluid.

PMID- 15949064
TI  - A study of the prevalence of sexually transmitted infections and related
      conditions in pregnant women attending a sexual health service.
AB  - A retrospective study was undertaken of all women attending a sexual health
      service during their pregnancies in the year 2000 in order to find the prevalence
      of sexually transmitted infections (STIs) and other conditions commonly screened
      for in sexual health services among this population. Data relating to
      demographics, sexual health screen and infections diagnosed were collected. All
      new female registrations during the same period were additionally identified. The
      prevalence of disease in the two groups was compared. Data on 164 patients who
      attended during their pregnancies in the year 2000 were analysed. One STI was
      identified in 59 patients (36%), two infections in nine patients (5%) and three
      infections in three patients (2%). An increased prevalence of STIs was noted in
      those aged 25 and under, compared with those over 25 (P < 0.001). Prevalence of
      STIs increased with gestation (0.01 < P > 0.05). Prevalence of STIs was higher in
      pregnant women (63/164; 38.4%) compared with all new female registrations
      (1094/5273; 20.7%; P < 0.001) during the same period. Additionally, 8.5% of
      pregnant women had a negative screen compared with 20% of all new female cases.
      This study shows the prevalence of STIs to be significantly higher among the
      pregnant women as compared with all women attending. A trend towards more
      frequent occurrence of an STI was seen with increasing gestation and young age.
      Prospective studies are needed to verify these results among an unselected
      population of pregnant women.

PMID- 15949065
TI  - Concurrent gonococcal and chlamydial infections among men attending a sexually
      transmitted diseases clinic.
AB  - The aim of this retrospective study was to determine the prevalence of Chlamydia
      trachomatis co-infection in men with gonorrhoea attending a sexually transmitted
      diseases clinic in Edinburgh, Scotland. During the study period, there were 660
      cases of culture-proven gonorrhoea. Chlamydial DNA was detected in the urethra in
      79 (31%; 95% confidence interval [CI], 25-37%) heterosexual men who have sex with
      women (MSW); the median age was significantly lower than those with gonorrhoea
      alone (24.0 versus 30.0; P <0.0005). The prevalence of urethral chlamydial
      infection among MSW was significantly higher than among men who have sex with men
      (MSM) (32 [12%; 95% CI, 8-16%] of 268 MSM) (chi2 = 27.21; P <0.001). Sixteen
      (24%; 95% CI, 14-34%) of 68 MSM with rectal gonorrhoea had concurrent rectal
      chlamydial infection. The high prevalence of concurrent gonorrhoea and chlamydiae
      therefore warrants empirical treatment and/or testing for chlamydia in all men
      with urethral gonorrhoea.

PMID- 15949066
TI  - Is ritonavir boosting associated with gout?
AB  - Asymptomatic hyperuricaemia is associated with ritonavir therapy, but gout has
      rarely been reported. We present a retrospective cohort study of 1825 HIV
      positive patients seen at one inner London HIV clinic over a two-year period. In
      all, 18 patients had gout, of whom 15 were receiving antiretroviral therapy.
      Seven had predisposing risk factors for gout (e.g. pyrazinamide therapy,
      haematological malignancy). Of the remaining 11 patients, two were on no
      medication and eight (73%) were receiving ritonavir as a boosted protease
      inhibitor (PI). By comparison, 11% of HIV-positive patients without gout were
      receiving ritonavir (odds ratio = 22; confidence interval = 5-104). Seven of the
      18 patients had documented features of lipodystrophy and dyslipidaemia. Gout was
      seen in patients with known risk factors for gout or who were receiving ritonavir
      as a boosted PI and who also had lipodystrophy.

PMID- 15949067
TI  - Low prevalence of high-density lipoprotein cholesterol level < 1 mmol/L in non
      nucleoside reverse transcriptase inhibitor recipients.
AB  - Our objective was to compare the prevalence of high-density lipoprotein
      cholesterol (HDL-c) level < 1 mmol/L in non-nucleoside reverse transcriptase
      inhibitor (NNRTI) and protease inhibitor (PI) recipients in an unselected HIV
      positive population. All HIV-positive patients living in Oslo who attended our
      outpatient clinic from April 1, 2000 to April 1, 2001 were invited to a study of
      cardiovascular risk factors. In this substudy, 40 NNRTI recipients and 124 PI
      recipients were included. Prevalence of HDL-c <1 mmol/L was 7.5% in the NNRTI
      recipients compared with 35.5% in the PI recipients (P <0.001). In the
      multivariate analyses, use of NNRTI was a significant protective factor (odds
      ratio [OR] 0.17; 95% confidence interval [CI] 0.05-0.66; P = 0.01) and elevated
      triglycerides a significant risk factor (OR 3.40; 95% CI 1.47-7.86; P = 0.004)
      for low HDL-c level. Our study shows that NNRTI recipients have a more favourable
      HDL-c profile than PI recipients, even when possible confounding factors are
      taken into account.

PMID- 15949068
TI  - HIV/AIDS: occupational risk, attitude and behaviour of surgeons in southeast
      Nigeria.
AB  - Our objective was to evaluate the level of occupational risk, attitude and
      behaviour of surgeons towards HIV-infected patients. A questionnaire survey of
      264 randomly selected surgeons in training or in practice in five different
      health institutions in southeast Nigeria within a five-month period was carried
      out. A 94% response rate was obtained with completed questionnaires from 264
      surgeons. The respondents included obstetricians and gynaecologists (n = 78),
      general surgeons (n = 121), orthopaedic surgeons (n = 40), dental surgeons (n =
      10), ophthalmologists (n = 6), urologists (n = 5), and ear, nose and throat
      surgeons (n = 4). Of them, 31% (n = 82) were qualified surgeons in practice,
      while the remaining 69% (n = 182) were resident surgeons in training. In the past
      five years, 40.2% (n = 106) and 26% (n = 70) of the respondents reported needle
      stick injuries and blood splash, respectively, during surgery. The majority of
      the victims were resident surgeons, obstetricians and gynaecologists, and
      orthopaedic surgeons. Level of clinical experience and high patient blood loss
      are likely to contribute to this observation. In all, 89% (n = 236) were engaged
      in the risky practice of operating on patients with open wounds in their hand and
      the wounds were contaminated with blood in 5% of cases. During surgical
      procedures, all (100%) respondents wore protective apron, 65.2% (n = 172) wore
      double gloves and 30.3% (n = 80) used protective goggles. The use of double
      gloves and protective eye wear increased remarkably over the past decade,
      probably because the fear of occupational transmission of HIV was substantial. In
      total, 83% (n = 220) of the respondents had some reservations about treating
      patients infected with HIV, while 13.3% (n = 35) viewed them with fear. The
      remaining 3.4% (n = 9) had a more positive attitude towards HIV-infected
      patients. Further, 92% advocated preoperative screening, with special precaution
      during surgery, if the results are positive. In addition, 79.5% were of the view
      that infected patients should not be discriminated against in treatment, provided
      necessary protective materials are available. To ensure provision of these
      protective materials, 91% (n = 240) and 89.4% (n = 236) of the respondents
      favoured involvement of government and insurance agencies, respectively. In order
      to achieve a greater commitment from surgeons in developing countries towards
      caring for HIV-infected patients, there is a need for a comprehensive AIDS
      management package that would offer specific preventive and psychological
      training in care of HIV patients and provide requisite funds and resources.

PMID- 15949069
TI  - Increasing trends in HIV and TB rates in Odessa and the Ukraine.
AB  - Notification rates for HIV and tuberculosis (TB) have increased in the Ukraine
      and particularly in Odessa. In 1962, the incidence of TB in Odessa region was 178
      cases per 100,000 cases, declining to 73.0, 42.0 and 41.6 cases per 100,000 in
      1972, 1982 and 1992, respectively. In 2002, TB incidence and prevalence were 80.4
      and 330.1/100,000 population, respectively. TB mortality in the port almost
      doubled from 10.2/100,000 to 21.6/100,000 between 1990 and 2001. In 2002, the HIV
      incidence and prevalence and AIDS incidence and prevalence were 46.4 and 241.0
      cases/100,000 population and 14.5/100,000 and 26.9/100,000, respectively. There
      are increasing numbers of TB cases co-infected with HIV (200 in 2002), suggesting
      that the HIV and TB epidemics are converging. Significant effort is needed for
      the effective control of these two outbreaks to prevent high levels of morbidity
      and mortality from these diseases.

PMID- 15949070
TI  - The adherence to antiretroviral treatment evaluated from a hospital pharmacy:
      importance of the protease inhibitors pharmacological class.
AB  - The goal of this study was to develop an evaluation method of antiretroviral
      treatment adherence from a hospital pharmacy and to identify one or more factors
      that influenced this adherence, such as patient or treatment characteristics. The
      HIV patients included in this study were based, for the major part, in Saint
      Andre hospital and collected their medication from this hospital pharmacy. They
      were all delivered a renewable prescription that should have comprised two
      successive delivery stamps. A total of 186 patients was included. For the
      adherence analysis, the delay between two successive deliveries was measured. We
      have specified three different categories of patients: adherent, non-adherent and
      intermediate, according to a definition of adherence accepted by many authors. We
      have demonstrated that the only antiretroviral therapeutic class associated with
      poor adherence was the protease inhibitors, in particular nelfinavir, which
      requires food to be taken at the time of administration. This can pose
      difficulties for those patients who lunch at their workplace and consequently
      affect adherence. This study allowed us to demonstrate that a less subjective
      adherence evaluation can be easily carried out from a hospital pharmacy.

PMID- 15949071
TI  - Mycoplasma-enhanced priapism in mice.
AB  - Priapism seen occasionally in mice used in various mycoplasmal studies over
      several years prompted further investigation. Of six strains of young adult male
      mice inoculated intravenously with Mycoplasma pulmonis, of murine origin,
      priapism was seen only in CBA mice, penile erections persisting in some for seven
      to 44 weeks. A few mice given broth medium without mycoplasmas also developed
      priapism, and mice given five mycoplasmal species, of human origin, developed the
      condition in a way similar to these controls. However, those given M. pulmonis
      developed priapism earlier and of longer duration than other mice, suggesting
      that it was an enhancing factor. The duration of the phenomenon is remarkable
      and, as yet, has no clear explanation.

PMID- 15949072
TI  - Audit on the management of epididymo-orchitis by the Department of Urology in
      Edinburgh.
AB  - Epididymo-orchitis among men younger than 35 years is mainly caused by chlamydial
      infection. National guidelines for the management of this condition have been
      published. The aim of this study was to audit the management of epididymo
      orchitis in a major teaching hospital. To this end we performed a retrospective
      study of patients with epididymo-orchitis admitted to the Department of Urology
      in the Western General Hospital, Edinburgh between 1998 and 2003. Case-notes of
      108 cases of epididymo-orchitis were reviewed. The diagnosis was established by
      ultrasound in 94% of cases. Patients were not tested routinely for chlamydial
      infection and the majority of men younger than 35 years were treated
      inappropriately with ciprofloxacin. The management of patients younger than 35
      years was not in accordance with the recommendations of national guidelines.
      Chlamydia trachomatis is sexually transmissible and is not responsive to
      ciprofloxacin. As a result of this audit, each patient will be tested for
      chlamydial infection and men younger than 35 years will be treated with
      ofloxacin. Sexual partners of patients with chlamydial infection will be treated
      in the department of genitourinary medicine.

PMID- 15949073
TI  - Genital warts in a transsexual.
AB  - Genital warts are the commonest sexually transmitted viral infection seen in
      genitourinary medicine clinics. As common as warts are, with extensive previous
      studies, literature searches on genital warts in transsexuals were unfruitful.
      Due to the nature and rarity of such a case, it was felt that it would be
      interesting to detail its management.

PMID- 15949074
TI  - Patient-acquired hepatitis B and HIV following erectile dysfunction therapy.
AB  - This is believed to be the first reported case of HIV and hepatitis B acquired
      heterosexually using erectile dysfunction drugs.

PMID- 15949075
TI  - CCR2/64I mutation detection in a HIV-1-positive patient with slow CD4 T-cell
      decline and delay in disease progression.
AB  - Chemokine receptor genetic mutations are among the factors which have been shown
      to influence human susceptibility to HIV-1 infection and progression. The CCR2
      64I mutation has been shown to delay HIV-1 disease progression in some studies.
      Here we show evidence of delayed disease progression, reflected in maintenance of
      a stable viral load and a slow CD4 T-cell decline, in a patient with the CCR2-64I
      gene. We then consider the potential value of identifying these genetic defects
      in the era of fusion/entry inhibiting therapeutics.

PMID- 15949076
TI  - Microbiology and antimicrobial management of sinusitis.
AB  - Sinusitis generally develops as a complication of viral or allergic inflammation
      of the upper respiratory tract. The bacterial pathogens in acute sinusitis are
      Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis,
      while anaerobic bacteria and Staphylococcus aureus are predominant in chronic
      sinusitis. Pseudomonas aeruginosa has emerged as a potential pathogen in
      immunocompromised patients and in those who have nasal tubes or catheters, or are
      intubated. Many of these organisms recovered from sinusitis became resistant to
      penicillins either through the production of beta-lactamase (H. influenzae, M.
      catarrhalis, S. aureus, Fusobacterium spp., and Prevotella spp) or through
      changes in the penicillin-binding protein (S. pneumoniae). The pathogenicity of
      beta-lactamase-producing bacteria is expressed directly through their ability to
      cause infections, and indirectly through the production of betalactamase. The
      indirect pathogenicity is conveyed not only by surviving penicillin therapy, but
      also by 'shielding' penicillin-susceptible pathogens from the drug. The direct
      and indirect virulent characteristics of these bacteria require the
      administration of appropriate antimicrobial therapy directed against all
      pathogens in mixed infections. The antimicrobials that are the most effective in
      management of acute sinusitis are amoxycillin-clavulanate (given in a high dose),
      the newer quinolones (gatifloxacin, moxifloxacin) and the second generation
      cephalosporins (cefuroxime, cefpodoxime, cefprozil or cefdinir). The
      antimicrobials that are the most effective in management of chronic sinusitis are
      amoxycillinclavulanate, clindamycin and the combination of metronidazole and a
      penicillin.

PMID- 15949077
TI  - Paediatric otolaryngology services in the UK: a postal questionnaire survey of
      ENT consultants.
AB  - Approximately half a million children in England and Wales receive in-patient or
      day-case surgical treatment annually. Otolaryngology is the surgical specialty
      that provides the greatest number of episodes of such care. As 30-50 per cent of
      our total volume of work is paediatric, we feel it is important to assess current
      attitudes to paediatric otolaryngological practice. In its year 2000 document
      Children's Surgery: a First Class Service, The Royal College of Surgeons (RCS) of
      England sets out recommendations on how children's surgical services should be
      delivered in the UK. A postal questionnaire was sent to all UK-based ENT
      consultant members of the British Association of Otorhinolaryngologists-Head and
      Neck Surgeons (BAO-HNS). The questionnaire was designed to assess the current
      practice of paediatric otolaryngology in the UK with an emphasis on the RCS
      recommendations. Wide variations were found, and they are discussed with
      reference to the recommendations.

PMID- 15949078
TI  - Otologic side effects of drugs.
AB  - Otolaryngologic symptoms are common and patients presenting to the
      otolaryngologist will often be taking drugs for the treatment of unrelated
      diseases. As a doctor, one must not forget the potential of these drugs to cause
      otologic side effects and, in some cases, to be the cause of the presenting
      symptom. We performed a comprehensive search of the British National Formulary
      and Electronic Medical Compendium websites to classify the otologic side effects
      caused by drugs. Not all the data were found at both websites. We have compiled
      all the data together, subclassified them and produced a review of the otologic
      side effects of drugs, in table form.

PMID- 15949079
TI  - One-stage nasal and multi-level pharyngeal surgery for obstructive sleep apnoea:
      safety and efficacy.
AB  - A collapsible airway is often the common denominator in sleep-disordered
      breathing (SDB). The upper respiratory tract includes the nasal passage,
      nasopharynx, oral cavity, oropharynx, base-of-tongue region and the hypopharynx.
      It is believed that the highest amount of resistance in the upper respiratory
      tract is in the nasal cavities, and particularly the nasal valve. Most authors
      believe that when considering surgical options for patients with obstructive
      sleep apnoea (OSA) it is imperative to correct nasal pathology together with the
      other sites of airway obstruction. In this retrospective study, I sought to
      investigate the safety and efficacy of one-stage nasal and multi-level pharyngeal
      surgery. I compared two groups of patients: group 1, receiving one-stage nasal
      and multi-level pharyngeal surgery; and group 2, receiving only multi-level
      pharyngeal surgery. In group 1, nine out of 12 patients (75 per cent) met the
      criteria for surgical success, with a mean pre-operative apnoea-hypopnoea index
      (AHI) decreasing from 36.3 to 8.9 post-operatively (p<0.0002), while in group 2,
      25 out of 40 patients met the surgical success criteria (62.5 per cent), with
      their mean AHI decreasing from 52.6 to 10.2 (p<0.0000). When comparing the
      surgical success rates between the two groups, it was not statistically
      significant, at p>0.106. There were no postoperative respiratory-related
      complications despite having bilateral nasal Merocel (tampon) packing in place
      (in group 1), and none of the patients in either group had any desaturation,
      hypoxaemia, apnoea or OSA-related complications. This series suggests that, with
      adequate post-operative monitoring, it is both safe and efficacious to perform
      both nasal and multi-level pharyngeal surgery in the one surgical session.

PMID- 15949080
TI  - Fat graft myringoplasty: a cost-effective but underused procedure.
AB  - OBJECTIVES: The objective of this study was to evaluate the success of fat graft
      myringoplasty and to discuss the utilities and advantages of a fat graft in
      primary versus revision myringoplasties. METHODS: Eighteen patients who had not
      had previous otological surgery, and twelve patients whose tympanic membrane
      perforations have persisted despite myringoplasty with temporalis fascia were
      included in this prospective clinical trial. All patients were treated by fat
      graft myringoplasty and followed up for one year. RESULTS: Successful closure of
      the perforation was obtained in 82.4 per cent of the ears at the final follow up.
      The success rate in the group of patients who had not had previous otological
      surgery was higher than those of revision cases. CONCLUSIONS: Adipose tissue
      provides the basic requirements for grafting of the tympanic membrane, with its
      own favourable characteristics. Fat graft myringoplasty is a cost-effective
      alternative in small perforations of the tympanic membrane, including revision
      cases.

PMID- 15949081
TI  - Is there a role for more day-case septal surgery?
AB  - A significant number of patients requiring septal surgery are still undergoing in
      patient procedures at a time when pressures on in-patient beds are increasing. A
      retrospective audit of 109 patient case notes was performed to assess the
      potential for day-case surgery amongst patients undergoing septal surgery in the
      ENT department at Leicester Royal Infirmary. The other aims of the audit were to
      assess the overall complication rates, because these have implications for day
      case surgical patients, and to see which patients should be selected. Overall,
      the study group had a haemorrhage rate of six per cent and a potential for 92 per
      cent of cases to be performed as day-case procedures. Day-case septal surgery, if
      utilized appropriately, has great potential in reducing the pressure on inpatient
      beds.

PMID- 15949082
TI  - A prospective double-blind randomized controlled trial of the effect of topical
      bupivacaine on post-operative pain in bilateral nasal surgery with bilateral
      nasal packs inserted.
AB  - To ascertain whether local anaesthetic use is of clinical benefit in nasal
      surgery, a prospective double-blind randomized controlled trial of topical
      bupivacaine on post-operative pain in patients packed after bilateral nasal
      surgery was carried out. Each patient received a bupivacaine-soaked and a saline
      soaked Merocel pack, thereby acting as their own control. Power analysis
      ascertained the number of patients required to enter the trial to detect a
      statistically significant difference in pain. Fifty-seven patients completed the
      trial. Visual analogue scales determined the level of post-operative pain at
      different time points in each nostril. Less pain was demonstrated in nostrils
      containing bupivacaine-soaked packs compared with saline-soaked packs at two
      hours (p < 0.0001), four hours (p = 0.0183) and six hours (p = 0.0476) post
      operatively. Although not statistically significant, less pain was noted on pack
      removal on the local anaesthetic sides. These results provide clinical-based
      evidence for the use of bupivacaine as a local anaesthetic in reducing pain
      following nasal surgery with packing.

PMID- 15949083
TI  - Critical clinical appraisal of the role of ultrasound guided fine needle
      aspiration cytology in the management of parotid tumours.
AB  - OBJECTIVE: Fine needle aspiration cytology is a well established tool for
      investigating many head and neck conditions. Its application in parotid tumours
      is, however, controversial. This article is aimed at defining the role of
      ultrasound guided fine needle aspiration cytology (FNAC) in the diagnostic work
      up of parotid tumours. The accuracy and utility of FNAC of parotid tumours was
      also assessed. DESIGN: Retrospective case note review. SETTING: District general
      hospital. PARTICIPANTS: Review of 69 patient records who had parotid surgery
      under one surgeon's care (JS). Clinical opinion, FNAC results and final pathology
      findings were examined. MAIN OUTCOME MEASURES: The results of the FNAC were
      compared to the histopathological diagnosis obtained from the surgical specimen.
      RESULTS: Histological evaluation revealed 13 malignant tumours and 56 benign
      lesions. The overall sensitivity of FNAC was 84.6 per cent and specificity was
      96.4 per cent. We noted 11 true positive, 54 true negative, two false negative
      and two false positive results. Positive predictive value for diagnosing
      malignancy was 84.6 per cent and negative predictive value for malignancy was
      96.4 per cent. The overall accuracy of FNAC of parotids in this study was 94.2
      per cent. CONCLUSIONS: FNAC results provide useful preoperative information. FNAC
      enables more reliable patient counselling and reduces pathological surprises. Pre
      operative recognition of malignant tumours may help prepare both the surgeon and
      patient for an appropriate surgical procedure. Its enhancement of the pre
      operative recognition of malignant parotid tumours may alert more stringent
      attention to the operative margin and hence better tumour clearance. Ultrasound
      guided FNAC was found to be highly specific for malignancy and its sensitivity
      for malignancy was good.

PMID- 15949084
TI  - Student-perceived benefit from otolaryngology theatre attendance.
AB  - The value of theatre attendance by undergraduates is uncertain. This study aimed
      to evaluate the perceived benefits of attending operating theatre sessions during
      undergraduate otolaryngology attachments. The study comprised a questionnaire
      survey carried out in a university medical school. Fourth-year medical students
      were asked to complete a questionnaire at the end of their two-week attachment in
      otolaryngology. Completed questionnaires were returned by 152 students. The three
      most common student expectations were to see and learn common ENT operations, to
      see the anatomy involved and to learn about the disease being operated upon.
      Sixty per cent of students reported that their expectations had been met. On a
      Likert scale from 1 (strongly disagree) to 7 (strongly agree), the importance of
      theatre attendance as part of the curriculum was rated to be 4.7 (95 per cent
      confidence interval (CI) = 3.7 to 4.2) and the satisfaction of educational needs
      in operating theatre teaching was rated to be 3.9 (95 per cent CI = 3.7 to 4.2).
      Students perceived attending otolaryngology theatre sessions to be beneficial.
      This information is important in the planning of the otolaryngology undergraduate
      curriculum.

PMID- 15949085
TI  - Deep neck abscess: a prospective study of 54 cases.
AB  - Deep neck abscesses (DNAs) continue to be commonly encountered in developing
      countries like India. This study was conducted to determine the changing trends
      within our population with respect to presentation, aetiology, location and
      microbiology of DNAs. Fifty-four patients with DNAs who were managed at the
      Department of ORL and H&N Surgery in our hospital between May 2002 and December
      2002 formed the basis of the study. We observed that the high incidence of DNAs
      could be attributed to lack of awareness, illiteracy and poverty among patients,
      along with the poor primary health infrastructure. We also recommend early
      surgical intervention in these cases to decrease the prevalence of complications.

PMID- 15949086
TI  - Simultaneous reconstruction of large skin and mucosal defect following head and
      neck surgery with a single skin paddle pectoralis major myocutaneous flap.
AB  - The pectoralis major myocutaneous (PMMC) flap is commonly used for head and neck
      reconstruction especially in impoverished nations. PMMC is a sturdy pedicled flap
      with relatively fewer complications, the learning curve is short and no
      specialized training in microvascular surgery is needed in order to use this
      flap. In a defect that requires a large skin and mucosal lining the authors
      routinely use either a bi-paddle PMMC or a combination of PMMC (for the mucosal
      lining) and a delto-pectoral flap (for the skin defect). It is indisputable that
      free tissue transfer is a better way of reconstruction for the majority of most
      such defects. Unfortunately, not all patients can be offered this form of
      reconstruction due to the cost, time, expertise and infrastructural constraints
      in high volume centres such as ours. Bi-paddling of PMMC is hazardous in obese
      males and most female patients. In such patients the skin defect is reconstructed
      usually by the delto-pectoral (DP) flap but this, for obvious reasons, is less
      welcomed by the patients. The authors suggest a technique wherein mucosal lining
      is created by the myofascial lining (inner surface) of the flap and the skin
      defect is reconstructed by the skin paddle of the single paddle PMMC. It should
      be considered wherever a DP flap is unacceptable, or bi-paddling or free tissue
      transfer is not possible.

PMID- 15949087
TI  - A simple method for preparing an ear wick.
AB  - We present a simple method for preparing an ear wick for treating otitis externa
      in ENT outpatient clinics. In our experience, this method is efficient,
      economical and clean, and ensures an equal distribution of the medication along
      the wick.

PMID- 15949088
TI  - Genetically-induced deep venous thrombosis presenting as acute mastoiditis.
AB  - Sigmoid sinus thrombosis (SST) usually follows acute as well as chronic otitis
      media with coalescent mastoiditis. A singular case of noncoalescent mastoiditis
      complicated with thrombosis of deep cerebral sinuses occurring in a young child
      is presented. A genetic thrombophilic disorder (prothrombin G20210A allele
      mutation) was identified as the predisposing factor for this unusual
      complication. Particular emphasis is placed on the course of the disease, which
      showed regression only after surgical exploration and additional anticoagulant
      therapy. We conclude that a thorough and early assessment of coagulation factors
      should always be performed, especially in the population at risk, in order to
      rule out unusual aetiologies of these rare but still life-threatening
      pathological processes.

PMID- 15949089
TI  - Tuberculosis of the parotid gland.
AB  - Tuberculosis of the parotid gland is very rare and clinically indistinguishable
      from a neoplasm. Thus the diagnosis of parotid gland involvement with
      tuberculosis has traditionally been made after surgical resection. We present a
      case which was diagnosed on fine needle aspiration cytology and managed
      medically.

PMID- 15949090
TI  - Initial presentation and fatal complications of linear IgA bullous dermatosis in
      the larynx and pharynx.
AB  - Two cases of linear IgA bullous dermatosis initially presenting as ulcerative
      lesions in the larynx and pharynx are reported. It was difficult to diagnose and
      treat the lesions, but they were finally diagnosed from the histopathological
      findings of accompanying skin lesion specimens. One of the patients required a
      tracheostomy due to increased airway stenosis by a laryngeal lesion. Despite
      general corticosteroid administration this could not be completely resolved,
      although partial opening of the glottis was observed, and the patient died of
      accidental tracheostomy tube complications during home care. Although there are
      no reports of this disease in the otolaryngological field, these rare diseases
      involving the skin and entire body should be considered in the differential
      diagnosis of laryngeal and pharyngeal ulcerative lesions, including airway
      stenosis. Furthermore, simple and safe procedures for relieving airway stenosis
      should be selected for rare and difficult-to-diagnose airway disease, prior to
      the final diagnosis.

PMID- 15949091
TI  - Cutaneous metastases from a hypopharyngeal malignancy.
AB  - We present an unusual case of carcinoma of the piriform fossa, presenting with
      cutaneous metastases. These metastases are very rare, present in the late stages
      of disease, and are usually associated with distant metastases and poor
      prognosis. They often suggest aggressive disease. We believe that cutaneous
      metastases from a malignancy in the piriform fossa are more unusual than those
      from other sites of the head and neck.

PMID- 15949092
TI  - Endovascular embolization of a traumatic arteriovenous fistula of the superficial
      temporal artery.
AB  - Arteriovenous fistula of the superficial temporal artery is a rare condition most
      commonly caused by trauma. Traditional surgical treatment has been superseded by
      endovascular embolization. We present the case of a 40 year-old man with a
      traumatic arteriovenous fistula of the superficial temporal artery who was
      treated by endovascular embolization. The advantages of this approach are
      discussed, along with a brief history of the condition.

PMID- 15949093
TI  - Gradenigo's syndrome: successful conservative treatment in adult and paediatric
      patients.
AB  - A triad of retro-ocular pain, discharging ear and abducens nerve palsy, as
      described by Gradenigo, has been recognized for 150 years. It has traditionally
      been treated with surgery, but recent advances in imaging, allied with improved
      antibiotic treatment, allow conservative management of these cases. We present
      two cases of Gradenigo's syndrome: a 6-year-old child and a 70-year-old man, both
      without cholesteatoma, who were managed without mastoidectomy. They both had full
      recovery of abducens nerve function, although this took 6 and 12 weeks,
      respectively. In order to manage patients with Gradenigo's syndrome safely,
      accurate diagnostic radiology is essential, and our findings are presented and
      discussed. With changing medical technology, a review of the diagnostic and
      treatment options for this rare but serious condition, is timely.

PMID- 15949094
TI  - Cerebellopontine angle arachnoid cysts in adult patients: what is the appropriate
      management?
AB  - Arachnoid cysts can occur at different intracranial sites, including the
      cerebellopontine angle (CPA). The incidence of arachnoid cysts is 1 per cent of
      all intracranial lesions. Recent advances in MRI (magnetic resonance imaging)
      scan techniques have led to CPA arachnoid cysts being more frequently diagnosed
      and with a higher degree of certainty. The need for further understanding of
      their natural history as well as for the development of a management rationale
      has been highlighted with this increased rate of diagnosis. We present a series
      of five adult patients with different clinical presentations attributed to CPA
      arachnoid cysts. These lesions have a characteristic location in the posterior
      inferior aspect of the CPA below the facial and vestibulocochlear nerves. These
      cysts did not show change in size on repeated MRI scan and the patients' symptoms
      did not progress over the period of follow up. Our findings would support a
      conservative management approach to the majority of these cysts.

PMID- 15949095
TI  - A group III steroid solution without antibiotic components: an effective cure for
      external otitis.
AB  - The present study was undertaken to compare the clinical benefits of prescribing
      ear drops containing 0.05% solution of betamethasone dipropionate (BD), and ear
      drops containing hydrocortisone with oxytetracycline hydrochloride and polymyxin
      B (HCPB), for topical treatment of external otitis. Fifty-one patients were
      enrolled in this open randomized, parallel-group, multicentre study, performed in
      eight different ENT departments. The patients were randomly assigned to one of
      the two treatment groups: BD (n = 26) and HCPB (n = 25). Only ENT specialists
      investigated the patients. Bacterial and fungal cultures were raised on days 1
      and 11, using swabbed material from ear canals. Twice daily the patients recorded
      their symptoms during the acute phase, using special diary cards.BD proved a
      significantly more effective cure than HCPB during the acute phase of external
      otitis and afforded a lower relapse frequency during a six-month follow-up
      period. The patients of the BD group were significantly less troubled by itching
      (p < 0.01) than those in the HCPB group. On day 11, at the end of the acute
      phase, growth of bacteria (p = 0.03) and fungi (p < 0.01) was less frequent in
      the BD group than in the HCPB group. No serious adverse events occurred, and
      those minor events observed were comparable between the two groups.Our conclusion
      is that the group III steroid solution, BD, cured the external otitis more
      effectively than did the HCPB solution, whether infected by bacteria or by fungi.
      No difference was evident regarding adverse effects. Furthermore, price favours a
      solution without any antibiotic component. In view of these observations, a group
      III steroid solution ought to be the preferred remedy for external otitis,
      whether infected or not.

PMID- 15949096
TI  - Lignocaine as a topical analgesia for post-operative nasal pack removal: a
      prospective, randomized, double-blind, controlled trial.
AB  - The objective of this study was to assess the efficacy of topical lignocaine in
      reducing the pain of pack removal after nasal surgery. Fifty-eight patients with
      Merocel nasal packs in situ after nasal surgery were randomized to receive 10 ml
      of either 2 per cent lignocaine or 0.9 per cent saline on the packs 10 minutes
      prior to their removal and the pain experienced on their removal was recorded on
      a visual analogue scale. The median pain score was 3.4 in the lignocaine group
      and 2.9 in the saline group with no statistical evidence of a difference between
      the two groups. There was no statistical evidence of an association between the
      group and the operation performed, the use of intra-operative Moffat's solution
      or the use of post-operative oral analgesia. We conclude that lignocaine used in
      this way does not reduce the pain of pack removal after nasal surgery.

PMID- 15949097
TI  - Is it necessary to differentiate tinnitus from auditory hallucination in
      schizophrenic patients?
AB  - Although the definitions of subjective tinnitus and auditory hallucination are
      very similar, the origins and underlying causes of each symptom clearly differ.
      This study examined whether the differentiation of tinnitus from auditory
      hallucination is necessary for the proper management of these symptoms in
      schizophrenic patients. We investigated the characteristics of auditory
      hallucinations in 15 schizophrenic patients, and measured their pure-tone hearing
      levels and auditory brainstem responses (ABR). The average hearing level was 20.6
      +/- 16.2 dB, with a mild decrease at high frequencies. We classified the patients
      into three groups: pure hallucination, tinnitus, and hallucination plus tinnitus.
      Eight patients (53.3 per cent) complained of pure hallucination and only one of
      them had a mild hearing loss. Hearing deficits were observed in six of seven
      tinnitus patients. Abnormal findings of ABR were found only in the pure
      hallucination group. The results suggest that tinnitus should be differentiated
      from auditory hallucination in the evaluation of schizophrenic patients.

PMID- 15949098
TI  - Operative training in otolaryngology in the United Kingdom: a specialist
      registrar survey.
AB  - OBJECTIVE: To assess the current status of operative training for otolaryngology
      specialist registrars in the United Kingdom. DESIGN: Web-based questionnaire
      survey. PARTICIPANTS: All otolaryngology specialist registrars in the United
      Kingdom. MAIN OUTCOME MEASURES: The overall satisfaction with operative training
      was assessed as well as the number of operations performed and level of
      competency in stage-specific procedures, as defined by the Joint Committee for
      Higher Specialist Training. RESULTS: Otolaryngology specialist registrars are
      generally satisfied with the quality of their operative training. The most
      important predictive factor of satisfaction with operative training was the
      number of theatre sessions per week. The vast majority of registrars (92 per cent
      by the end of year one, 73 per cent at the end of years two to four) appear to
      attain all the stage-appropriate surgical competencies during the first four
      years. However, with respect to the last two years of registrar training, only 26
      per cent can perform all the designated (complex) procedures. There are no
      significant differences between deaneries or geographic regions in the overall
      satisfaction rates, number of operative sessions, number of operations performed
      or operative competencies attained. CONCLUSION: It appears that the Specialist
      Advisory Committee (SAC) is generally successful in maintaining common operative
      training standards and providing a homogenous training environment. During the
      first four years registrars attain an appropriate level of general training while
      the last two years are mainly devoted to subspecialty interests.

PMID- 15949099
TI  - Endoscopic sinus surgery for antrochoanal polyp using CO2 laser and/or
      microresector: a long-term result.
AB  - Endoscopic sinus surgery procedure using CO2 laser and/or microresector for
      paediatric and adult chronic sinusitis with antrochoanal polyp (ACP), with long
      term follow-up, was examined. Twelve children and 13 adults underwent the
      surgical procedure. The following two techniques were used to remove the antral
      portion of an ACP with a 70 degrees endoscope: (1) CO2 laser--The base of the ACP
      was vaporized and removed via an enlarged natural ostium with a pipe-guide
      handpiece with a deflective tip. (2) Microresector--The ACP was resected via an
      enlarged natural ostium and/or nasoantral window opened under the inferior
      turbinate with the curved and straight blade of a microresector. In the
      endoscopic follow up for 10 to 57 months, no patient who underwent the primary
      surgery required reoperation for ACP recurrence. One out of the seven patients
      who underwent secondary surgery required a revised operation with microresector
      and CO2 laser.

PMID- 15949100
TI  - Otic barotrauma from air travel.
AB  - Otic barotrauma occurring during air travel involves traumatic inflammation of
      the middle ear, caused by a pressure difference between the air in the middle ear
      and the external atmosphere, developing after ascent or more usually descent. The
      pressure difference occurs because of failure of the eustachian tube to
      equilibrate middle ear and atmospheric pressures. It is a common problem,
      presenting with ear fullness, otalgia and deafness. Severe cases may result in
      tympanic membrane perforation and even round window membrane rupture. Of three
      randomized controlled trials, one showed that oral pseudoephedrine decongestants
      reduced otalgia in adults with recurrent ear pain during air travel, whilst
      another found that oral pseudoephedrine did not decrease in-flight ear pain in
      children. The third trial showed that oxymetazoline decongestant nasal spray,
      taken 30 minutes before descent, did not produce a statistically significant
      reduction in symptoms of barotrauma in adults with recurrent ear pain during air
      travel. We review the causes, prevention and treatment of this condition.

PMID- 15949101
TI  - Association between methylenetetrahydrofolate reductase polymorphisms, alcohol
      intake and oropharyngolaryngeal carcinoma in northern Italy.
AB  - Folate metabolism dysregulation may lead to abnormal cell proliferation and
      predispose to carcinogenesis by inducing DNA hypomethylation. Folate pathways may
      be modified by polymorphisms in relevant genes, such as that for
      methylenetetrahydrofolate reductase (MTHFR), or by alcohol consumption. We
      investigated the relationship between MTHFR mutations at nucleotides C677T and
      A1298C, which cause reduced MTHFR enzyme activity, and susceptibility to
      oropharyngolaryngeal carcinoma in 65 patients and 100 controls. We isolated DNA
      from peripheral blood leukocytes. In oropharyngolaryngeal carcinoma cases the
      C677T heterozygous genotype was more frequent (p = 0.018), the allele frequency
      of MTHFR 677T was greater (p = 0.019) and the genotype 677TT/1298AA was more
      frequent (p = 0.001). A higher risk of carcinoma was found in the case of
      moderate drinkers with mutant MTHFR homozygosis or double heterozygosis (OR =
      21.2 and OR = 9.1, respectively; p trend = 0.002), and the association was
      maintained for the different cancer sites (glottic, supraglottic, oropharyngeal).
      Our findings support the hypothesis that the interaction of alcohol intake and
      MTHFR polymorphisms might contribute to susceptibility to carcinogenesis of the
      oropharyngolaryngeal tract.

PMID- 15949102
TI  - Referral letters: are we prioritizing consistently?
AB  - OBJECTIVES: To determine the levels of intra- and inter-grade variability of the
      vetting of general practice (GP) letters as well as the intra-rater reliability
      of letter prioritization. DESIGN: Prospective assessment of letter vetting and
      questionnaire survey. SETTING: Three otolaryngology secondary referral centres in
      Bristol and Bath, UK. PARTICIPANTS: Twelve consultants, nine registrars, four
      staff and associate specialists (SAS) and 16 senior house officers (SHOs) in
      otolaryngology. METHODS: Fifty GP letters (not including 'fast-track' referrals)
      addressed to one of the ENT departments were chosen sequentially. These were
      anonymized, photocopied and included in the questionnaire to all participating
      staff. Participants were asked to vet the letters as 'urgent', 'soon' or
      'routine' according to supplied waiting time criteria. The same letters were sent
      out again six weeks later. RESULTS: There was no significant difference between
      grades for the mean number of letters vetted into each category. Intra-grade
      variability was high; the number of letters vetted urgent varied from one out of
      50 to 15 out of 50 for the consultants. The intra-rater reliability was high.
      CONCLUSION: The grade of trainee seems to make little difference with regard to
      ability to prioritize referrals, but within grades there is little agreement on
      what constitutes an urgent referral. We suggest further research, looking at the
      final outcome of patients, needs to be done to try to establish evidence-based
      guidelines to assist with letter vetting.

PMID- 15949103
TI  - Experimental selective posterior semicircular canal laser deafferentation.
AB  - In this experimental study, we attempted to perform selective deafferentation of
      the posterior semicircular canal ampulla of guinea pigs using carbon dioxide
      laser beam. The results of this study document the efficacy of this procedure in
      achieving deafferentation of the posterior semicircular canal safely with regards
      to the other semicircular canals, the otolithic organ and the organ of hearing.
      Moreover, the procedure is performed with relative ease compared with other
      procedures previously described for selective deafferentation of the posterior
      semicircular canal. The clinical application of such a procedure for the
      treatment of intractable benign paroxysmal positional vertigo in humans is
      suggested.

PMID- 15949104
TI  - Management of hearing loss in Apert syndrome.
AB  - BACKGROUND: Apert syndrome is one of the craniosynostosis syndromes, with a birth
      prevalence estimated to be between 9.9 and 15.5/million, and accounts for 4.5 per
      cent of craniosynostoses. Although conductive hearing loss is common in Apert
      syndrome there are contradicting reports regarding the cause of this hearing
      loss. There is also no detailed information available on the management of
      hearing loss in Apert syndrome. MATERIALS AND METHODS: A retrospective analysis
      of case notes of Apert syndrome patients seen between 1970 and 2003 at Great
      Ormond Street Children's Hospital, London, was undertaken. RESULTS: Seventy case
      notes were obtained. The incidence of congenital hearing impairment was between 3
      and 6 per cent. Almost all patients had otitis media with effusion (glue ear),
      which tended to persist into adult life. More than 56 per cent of cases developed
      permanent conductive hearing loss by 10-20 years. Repeated grommet insertion was
      common; even though 35 per cent had trouble with ear discharge and persistent
      conductive hearing loss. Statistically, grommets made no difference to the risk
      of developing permanent hearing loss. CONCLUSION: This study, of the largest
      number of Apert syndrome cases assembled to date, showed that early optimization
      of hearing with possible hearing aids needs to be considered. Repeated grommet
      insertion does not help in optimizing hearing, especially if ear discharge
      complicates the picture.

PMID- 15949105
TI  - Long-term effects of the Meniett device in Meniere's disease: the Western
      Australian experience.
AB  - OBJECTIVES: Transtympanic pressure has been shown to influence endolymphatic
      hydrops. As endolymphatic hydrops plays a key role in Meniere's disease, a few
      studies, undertaken by the inventors, manufacturers and associates of the Meniett
      device, have demonstrated positive short-term effects of transtympanic pressure
      treatment via the Meniett device in medically intractable Meniere's disease. The
      aim of our study was to independently investigate the long-term efficacy and
      safety of transtympanic pressure treatment in the management of recalcitrant
      vertigo in Meniere's disease. DESIGN: Cross-sectional case study. SETTING:
      Tertiary referral centre. PARTICIPANTS: Eighteen patients with Meniere's disease,
      suffering from medically intractable symptoms. All patients in the study had
      Meniere's disease according to the criteria of the Committee on Hearing and
      Equilibrium of the American Academy of Otolaryngology, Head & Neck Surgery. MAIN
      OUTCOME MEASUREMENTS: Outcome and severity of symptoms were assessed, using the
      six-point functional scale and the vertigo visual analogue scale (VAS), as
      recommended by the Committee on Hearing and Equilibrium of the American Academy
      of Otolaryngology, Head & Neck Surgery. Changes of pure tone average thresholds
      and vestibular calorics before and during treatment with the Meniett device were
      recorded. The mean follow-up time was 18 months. RESULTS: Twelve out of 18
      patients showed significant improvement in the functional score and in the VAS.
      Five patients displayed an audiometric improvement, out of which three patients
      showed a pertaining significant hearing gain of more than 10 dB; the remainder
      had stable hearing levels. Of six patients without any improvement, four had
      previous invasive surgery for their Meniere's disease and two had previous
      vestibular ablation with gentamicin. No changes in vestibular function were
      noted. There were no complications during the treatment with the Meniett device.
      CONCLUSION: According to this independent study, the Meniett device seems to be a
      minimally invasive, non-destructive treatment tool, which can reduce vertigo and
      associated functional handicap in Meniere's disease. These effects are maintained
      up to 18 months after treatment so far. Previous surgical or chemical vestibular
      ablation procedures may adversely influence the effect of the Meniett device.

PMID- 15949106
TI  - A new head and neck surgical drain fixation technique.
AB  - We describe a simple technique of drain fixation in head and neck surgery using a
      beaded 2/0 nylon suture and a 'clove hitch' to achieve a non-slip fixation to the
      drain.

PMID- 15949107
TI  - Adenoidectomy with the coblator: a logical extension of radiofrequency
      tonsillectomy.
AB  - This paper describes a method of radiofrequency ablation of adenoid tissue using
      a coblator, comparing it with conventional and other newer methods of
      adenoidectomy. Its chief advantages are that it produces a bloodless field,
      precision of tissue removal and leads to less damage to surrounding tissues.

PMID- 15949108
TI  - Bilateral tension pneumothorax following rigid bronchoscopy: a report of an
      epignathus in a newborn delivered by the EXIT procedure with a fatal outcome.
AB  - We describe a case of a newborn baby with a prenatal diagnosis of an epignathus
      (oropharyngeal teratoma). With the potential for airway problems at birth, he was
      delivered by an elective EXIT (Extra Utero Intrapartum Treatment) procedure at 38
      weeks of pregnancy. The airway was secured and rigid bronchoscopy performed.
      Initially he was stable, but developed cardiorespiratory difficulties 40 minutes
      after birth and died from a cardiac arrest 17 minutes later. Tension pneumothorax
      is a devastating complication that can occur with lower airway manipulation for
      anaesthesia and rigid bronchoscopy. The addition of positive pressure during
      mechanical ventilation converts the pneumothorax into a tension pneumothorax. The
      possibility of tension pneumothorax should be entertained in a mechanically
      ventilated patient whose ventilatory pressures are increasing, with diminishing
      cardiac output. A complicated case is presented, where the diagnosis was missed
      with a fatal outcome.

PMID- 15949109
TI  - Recurrent squamous cell carcinoma in the neopharynx treated successfully with
      topical 5-fluorouracil.
AB  - We present the first reported case of a squamous cell carcinoma recurrence on a
      reconstructed flap in the pharynx treated successfully with topical chemotherapy.
      The patient, treated for a pharyngeal cancer with resection and reconstruction
      with a free radial forearm flap, and post-operative radiotherapy, developed a
      tumour on the flap more than two years after surgery. The recurrence was also
      squamous carcinoma, but there was only superficial infiltration. This was treated
      with 5-fluorouracil paste placed in the pharynx, with resolution of the tumour.
      The patient was alive and well more than 28 months after this treatment, with no
      sign of disease recurrence. Topical chemotherapy for treatment of oral cancer is
      well described for early disease, but we show that it may be a useful treatment
      in recurrent disease in selected patients.

PMID- 15949110
TI  - Indium111 pentetreotide single photon emission computed tomography (In111
      pentetreotide SPECT): a new technique to evaluate somatostatin receptors in
      chordomas.
AB  - Chordomas are rare neoplasms originating along the neuraxis. Although they do not
      usually show cytological atypia, metastases have been reported in 30 per cent of
      cases. Survival rates in cases of skull base locations are low, and local
      recurrence is common after local excision. Radiation therapy is used in post
      operative treatment and proton radiation therapy as the primary treatment. In the
      present paper we present the case of a 50-year-old Caucasian man affected by
      chordoma of the clivus, with liver and chest metastases, relapsed after several
      surgical local excisions, to discuss improvements in therapeutic and imaging
      techniques. Indium111 (In111) pentetreotide single photon emission computed
      tomography (SPECT) was employed to assess the presence of somatostatin receptors
      and to treat the tumour with radiolabelled Y90-DOTA-lanreotide. Imaging,
      performed 2 months afterwards, showed stable disease in the lungs but a local
      progression in the metastases, in comparison with pre-treatment uptake. These
      data suggest the usefulness of radiolabelled somatostatin analogues in the
      diagnosis and therapy of chordomas.

PMID- 15949111
TI  - Agenesis of the unilateral parotid gland associated with pleomorphic adenoma of
      the contralateral parotid gland.
AB  - Congenital absence of the parotid gland is extremely infrequent. We present here
      a case of unilateral parotid gland agenesis with pleomorphic adenoma of the
      contralateral parotid gland. Even though pleomorphic adenoma is the most common
      tumour of the parotid gland, to our knowledge this is the first case of these two
      conditions being seen together.

PMID- 15949112
TI  - Bilateral nasolabial cysts associated with recurrent dacryocystitis.
AB  - OBJECTIVE: Nasolabial cysts are rare, nonodontogenic, soft-tissue, developmental
      cysts occurring inferior to the nasal alar region. They are thought to arise from
      remnants of the nasolacrimal ducts and they are frequently asymptomatic. We
      report a rare case of bilateral nasolabial cysts accompanied by bilateral chronic
      dacryocystitis. CASE REPORT: A 48-year-old woman suffering from bilateral chronic
      dacryocystitis was referred to our department for endonasal
      dacryocystorhinostomy. She had undergone external dacryocystorhinostomy on the
      left side a few years earlier. Physical examination and computed tomography scan
      revealed nasolabial cysts bilaterally inferior to the nasal alar region. The
      cysts were removed via a sublabial approach and endoscopic dacryocystorhinostomy
      was performed on the right side. Ten months after surgery, the patient was
      asymptomatic. CONCLUSION: There may be a correlation, due to embryological
      reasons, between the presence of nasolabial cysts and the presence of chronic
      dacryocystitis. Both can be corrected surgically, under the same anaesthesia,
      without visible scar formation.

PMID- 15949113
TI  - Couple screening to avoid thalassemia: successful in Iran and instructive for us.

PMID- 15949114
TI  - Screening, surgical repair, and the management of abdominal aortic aneurisms.

PMID- 15949115
TI  - Medical screening society working groups.

PMID- 15949116
TI  - The prevention of neonatal group B streptococcal disease: a report by a working
      group of the Medical Screening Society.
AB  - Streptococcus agalactiae, or Lancefield group B streptococcus (GBS), is the most
      frequent cause of serious bacterial sepsis, including neonatal meningitis, in UK
      neonates. Early-onset neonatal GBS infection, but not late-onset, can be
      prevented by screening to identify high-risk pregnancies and administering
      penicillin during delivery. A vaccine has been developed as an alternative means
      of prevention but it is awaiting a randomized trial before being available for
      general use. In this review we examine the published literature to assess the
      morbidity and mortality attributable to neonatal GBS infection, quantify the
      screening performance of the two alternative modes of screening (microbiological
      and risk factor based), review the evidence on the efficacy of the vaccine, and
      estimate the numbers of deaths and cases of serious disability that each strategy
      in turn might prevent in the UK, in order to assess the most effective means of
      prevention for the UK.

PMID- 15949117
TI  - Antenatal thalassaemia carrier testing: women's perceptions of "information" and
      "consent".
AB  - OBJECTIVES: To explore the attitudes of a sample of pregnant women in the UK
      towards informed consent for antenatal thalassaemia carrier testing and perceived
      pre-test information needs for such testing. SETTING: The study was conducted in
      two cities in the North of England, where participants were recruited via
      Midwifery and Genetic services. METHOD: In all, 110 Pakistani women tested and
      not found to be thalassaemia carriers completed a questionnaire, 14 of whom were
      also interviewed. Thirty-six women identified as carriers or possible carriers
      completed a questionnaire and were interviewed. The questionnaires assessed
      whether women were aware that they had been tested for thalassaemia carrier
      status, whether they were asked for their consent for such testing, and their pre
      test information preferences. The interviews explored women's beliefs about
      "informed consent" in more depth. RESULTS: Women had received little or no pre
      test information and said that they would have preferred to be informed that they
      were being tested, but they did not expect, or express a desire, to be asked for
      their informed consent. CONCLUSION: While information was important to women,
      consenting was not. Overall, women discussed "information" and "consent" as two
      separate issues, thus challenging assumptions around the term informed consent.
      Women wanted pre-test information because they wanted to know more about the
      tests that they would be having, not to use it to make decisions about whether to
      have the tests.

PMID- 15949118
TI  - Maternal anxiety and satisfaction following infant hearing screening: a
      comparison of the health visitor distraction test and newborn hearing screening.
AB  - BACKGROUND: Newborn hearing screening is currently replacing the health visitor
      distraction test (HVDT) conducted at eight months. Our previous research
      indicates that recall for further tests following newborn hearing screening can
      have a negative impact on the emotional well being of mothers, but it is not
      known if this is greater than that caused by recall following the distraction
      test. OBJECTIVE: To compare the impact on maternal anxiety and satisfaction of
      recall following newborn hearing screening and the HVDT. METHODS: Four groups
      participated: 27 mothers of babies receiving a satisfactory result and 21 mothers
      of babies recalled after the HVDT 26 mothers of babies receiving a satisfactory
      result and 16 mothers of babies recalled after newborn hearing screening.
      Questionnaires assessing maternal anxiety, worry and certainty about the babies'
      hearing, satisfaction with and attitudes towards the screening test were sent to
      mothers three weeks and six months following screening. RESULTS: Comparison of
      the effects of receipt of different results showed no significant differences in
      maternal anxiety, worry and certainty between the two tests. Those mothers whose
      babies had a newborn hearing screening test were significantly more satisfied,
      regardless of the result received. Those who received a satisfactory result on
      the newborn hearing screening programme also had more positive attitudes towards
      that screening test than those receiving a satisfactory result following the
      HVDT. CONCLUSION: These results suggest that newborn hearing screening does not
      have a more negative emotional impact than the HVDT.

PMID- 15949119
TI  - The immunochemical faecal occult blood test leads to higher compliance than the
      guaiac for colorectal cancer screening programmes: a cluster randomized
      controlled trial.
AB  - INTRODUCTION: We conducted a cluster-randomized trial aimed at assessing the
      effect of the type of faecal occult blood, guaiac or immunochemical test on
      screening compliance. METHODS: We sampled 130 general practitioners (GPs) who
      consented to participate in the trial. We randomly allocated half of them to the
      guaiac (Hemo-Fec) and half to the immunochemical test (OC-Hemodia). We sampled
      2/10 of the GPs' 50-75-year-old patients (n=7332) and randomly divided this
      population into half. One half was invited to be screened at the GP's office and
      the other to the nearest gastroenterology ward. The principal outcome was the
      percentage of returned tests. RESULTS: The immunochemical test had a compliance
      of 35.8% and the guaiac of 30.4% (relative risk [RR] 1.20; 95% confidence
      interval [CI] 1.02-1.44). The difference was mostly due to a higher probability
      of returning the sample: 93.8% and 88.6% for immunochemical and guaiac,
      respectively (RR 1.06; 95% CI 1.02-1.10). The guaiac test had a higher prevalence
      of positives (10.3% versus 6.3%, RR 0.603; 95% CI 0.433-0.837). There was a
      higher variability in the results obtained with the guaiac test compared with the
      immunochemical (F[1, 12] = 16.25; P=0.0017). CONCLUSIONS: Compliance is more
      likely with the immunochemical than the guaiac test, independent of the provider.
      Guaiac tests show a higher variability of the results among centres. The
      successful implementation of a screening programme requires a period of
      standardization of the test reading in order to avoid unexpected work overload
      for colonoscopy services.

PMID- 15949120
TI  - Acceptance of flexible sigmoidoscopy and colonoscopy for screening and
      surveillance in colorectal cancer prevention.
AB  - OBJECTIVES: To study an individual's experience of either flexible sigmoidoscopy
      (FS) or colonoscopy in a colorectal cancer prevention programme. METHODS:
      Consecutive individuals in a Bowel Cancer Prevention Programme, who had either an
      unsedated FS or a colonoscopy with sedation, participated in a prospective cross
      sectional questionnaire-based study. RESULTS: A total of 447 responses were
      obtained for 256 colonoscopies and 191 FSs (200 men [45%] and 247 women [55%]).
      The overall experience of colonoscopy was more comfortable than FS (75% versus
      18%; P<0.001). Embarrassment was low for both procedures (8%). There was no pain
      associated with colonoscopy and most individuals had a pain score of less than 3
      (11-point scale) for FS: 72% of men, 55% of women (P<0.001). Most individuals did
      not have a gender preference for the endoscopist. For colonoscopy, the worst part
      of the procedure was the preparation (78%) and for FS the preparation and the
      procedure ranked equally worst (30%). CONCLUSIONS: We have shown that colonoscopy
      with sedation is a very comfortable procedure. FS is more uncomfortable than
      colonoscopy; however, for the majority it is a tolerable experience. Women found
      FS only slightly more painful than men. The worst part of either procedure was
      the preparation. Embarrassment with either procedure was minimal. Both procedures
      are well tolerated and suitable for colorectal cancer screening.

PMID- 15949121
TI  - High participation rates are not necessary for cost-effective colorectal cancer
      screening.
AB  - BACKGROUND: In many countries high participation is an explicit target in
      screening programmes. The desire for high participation often appears to drive
      screening policy, although it is increasingly recognized that encouraging high
      participation may impinge upon the rights of an individual to make an informed
      choice. One argument offered in support of high participation is that it improves
      the cost-effectiveness of screening. This is questionable on theoretical grounds,
      and empirically there are conflicting results. Two recent cost-effectiveness
      models of faecal occult blood test (FOBT) screening for colorectal cancer (CRC)
      showed that cost-effectiveness was improved, another showed that cost
      effectiveness was worsened and a fourth indicated that cost-effectiveness was
      unaffected by increasing the participation rate. METHODS: We assessed the extent
      to which different levels and patterns of participation affect cost
      effectiveness, using decision modelling of three CRC screening with FOBT
      scenarios. We estimate the incremental cost-effectiveness (value for money)
      ratios for each scenario. RESULTS: The way in which participation is modelled,
      particularly assumptions made about the subsequent screening behaviour of non
      participants ("if" and "when" a non-participant attends for subsequent
      screening), affects the cost-effectiveness estimates for FOBT screening
      programmes. 100% participation in all screening rounds gives a cost per life year
      saved (LYS) of USD 9705. Cost-effectiveness is worst when people who do not take
      part in one screening round (initial or subsequent) never take part in any future
      rounds of screening. Under this scenario, a participation rate of 20% in second
      and subsequent rounds gives a cost per LYS of USD 29,500. Under more realistic
      assumptions, for example the attendance of even a small proportion of non
      participants in subsequent rounds, cost-effectiveness is more favourable and
      similar to that achieved for full participation: the scenario with a random
      participation rate of 20% in second and subsequent rounds for both participants
      and non-participants has a cost per LYS of USD 11,270. CONCLUSIONS: Contrary to a
      commonly held view, high participation in screening programmes is not necessary
      to achieve cost-effectiveness. Setting high target participation rates in
      screening programmes does not guarantee cost-effectiveness and may in certain
      circumstances reduce the cost-effectiveness.

PMID- 15949122
TI  - Second reading of screening mammograms increases cancer detection and recall
      rates. Results in the Florence screening programme.
AB  - OBJECTIVE: To assess double reading effectiveness in mammography screening.
      DESIGN: Retrospective study of 177,631 consecutive mammograms double read during
      1998-2003. SETTING: The Florence screening programme, involving 11 trained
      radiologists. Abnormalities reported by at least one reader prompted assessment.
      RESULTS: The referral rate was 2.89% for the first reader, 3.15% for the second
      reader, and 3.59% for either reader. Of 713 total cancers detected, 43 were
      suspected only by the second reader (6.4% relative, 0.024% increase in absolute
      detection rate) and had a lower stage compared to the first reader (pTis-pT1b =
      65.7 versus 52.0%): 41 were reviewed and classified (error type) as "minimal
      sign" in six, and "screening error" in 35 cases, or as BI-RADS 3 in one, 4a in
      20, 4b in 13, and 4c in three cases. The second reading cost was 2.70 per woman
      examined, or 11,168 per additional cancer detected (versus 11,585 at a single
      reading). DISCUSSION: Second reading is effective in detecting a limited number
      of additional cancer cases. Tumour stage (one-third over 1 cm in diameter) and
      review findings (high rate of "screening errors" and BI-RADS R4b-c categories)
      suggest that second reading detects small "difficult cases" as well as larger
      cancers missed due to fatigue or loss of attention. Second reading reduces
      screening specificity to a minor extent, and since cancer detection at second
      reading seems cost-effective the procedure is recommendable in routine practice.

PMID- 15949123
TI  - Mammographic screening only matters in the detectable preclinical period of
      breast cancer.

PMID- 15949125
TI  - Vitamin E inhibits hepatic oxidative stress, toxicity and hyperproliferation in
      rats treated with the renal carcinogen ferric nitrilotriacetate.
AB  - Ferric nitrilotriacetate (Fe-NTA) is a potent renal and hepatic tumor promoter,
      which acts through a mechanism involving oxidative stress. Fe-NTA when injected
      intraperitoneally into rats induces hepatic ornithine decarboxylase activity as
      well as hepatic DNA synthesis. Vitamin E is a well-known, lipid-soluble and chain
      breaking antioxidant which protects cell membranes from peroxidative damage. In
      this study, we investigated the protective effect of vitamin E, a major fat
      soluble antioxidant, against Fe-NTA-mediated hepatic oxidative stress, toxicity
      and hyperproliferation in Wistar rats. Animals were treated with two different
      doses of vitamin E for 1 week prior to Fe-NTA treatment. Vitamin E at a higher
      dose of 2.0 mg/animal/day showed significant reduction in Fe-NTA-induced hepatic
      ornithine decarboxylase activity, DNA synthesis, microsomal lipid peroxidation
      and hydrogen peroxide generation. Fe-NTA treatment alone caused depletion of
      glutathione, glutathione metabolizing and antioxidant enzymes in rat liver,
      whereas pretreatment of animals with vitamin E reversed these changes in a dose
      dependent manner. Taken together, our results suggest that vitamin E may afford
      substantial protection against the damage caused by Fe-NTA exposure and can serve
      as a potent preventive agent to suppress oxidant-induced tissue injury.

PMID- 15949126
TI  - The maize alternative oxidase 1a (Aox1a) gene is regulated by signals related to
      oxidative stress.
AB  - We isolated and characterized the expression of Aox1a, a member of the maize
      alternative oxidase (Aox) small multigene family. Aox1a consists of four exons
      interrupted by three introns and its promoter harbors diverse stress-specific
      putative regulatory motifs pointing to complex regulation and response to
      multiple signals. Responses of Aox1a to such signals were examined and compared
      with those of maize glutathione S-transferase I (GstI), a typical oxidative
      stress inducible gene. Potassium cyanide (KCN) and hydrogen peroxide (H2O2)
      induced a rapid increase of the Aox1a and GstI transcripts, which was persisted
      in prolonged treatment at high H2O2 concentration only for Aox1a. High
      concentration of salicylic acid (SA) and salicyl hydroxamic acid (SHAM) induced
      Aox1a mRNA only after prolonged exposure, while GstI displayed an early strong
      induction, which declined thereafter. Nitric oxide (NO) induced a high increase
      of Aox1a after prolonged exposure at high concentration, while GstI displayed a
      weak response. Our results show that multiple signaling pathways, involved in
      stress responses, also participate and differentially regulate Aox1a and GstI in
      maize. A ROS-depended signaling event may be involved, suggesting an essential
      role of Aox1a under oxidative stress in maize.

PMID- 15949127
TI  - The effects of topotecan on lipid peroxidation and antioxidant enzyme levels in
      rabbit liver tissue.
AB  - BACKGROUND: To evaluate the possible influence of topotecan therapy on lipid
      peroxidation and antioxidant enzymes in rabbit liver tissue, the levels of
      thiobarbituric acid reactive substances (TBARS) and activities of the antioxidant
      enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase
      (CAT) were investigated. METHODS: A total of 24 adult, healthy New Zealand
      rabbits were divided into three groups (n = 8). Topotecan was administered
      intravenously via the ear vein for 3 days at 0.25 mg/kg/day for the low-dose
      group and 0.50 mg/kg/day for the high-dose group; physiological saline was used
      for the control group. All animals were sacrificed on day 15. Livers were removed
      and homogenised. The homogenate supernatant was used for measurement of TBARS
      levels, and SOD, GSH-Px, and CAT enzyme activities (expressed as IU/mg protein).
      RESULTS: There were significant differences in the TBARS level and GSH-Px
      activity between control and the topotecan treatment groups. TBARS level of
      topotecan treatment groups was higher than control (89% and 126%, respectively, P
      = 0.001). It was also significantly higher in the high-dose group than the low
      dose group (20%; P = 0.011). GSH-Px activity was lower in the low- and high-dose
      topotecan groups than the control (42% [P = 0.002] and 65% [P = 0.001],
      respectively). Enzyme activity was lowest in the high-dose group and the
      difference was also significant when compared with the topotecan groups (40%; P =
      0.001). Although there was some decrease in SOD and CAT activities in the
      topotecan-treated groups, differences from the control group were not
      significant. CONCLUSIONS: These findings suggest that topotecan treatment results
      in an increase in lipid peroxidation and a decrease in antioxidant enzyme
      activities in healthy liver tissue from rabbits. We believe that the addition of
      antioxidants to topotecan therapy may reduce the harmful effects of topotecan on
      liver tissue.

PMID- 15949128
TI  - NMR studies of exchange between intra- and extracellular glutathione in human
      erythrocytes.
AB  - Glutathione is the main source of intracellular antioxidant protection in the
      human erythrocyte and its redox status has frequently been used as a measure of
      oxidative stress. Extracellular glutathione has been shown to enhance
      intracellular reduced glutathione levels in some cell types. However, there are
      conflicting reports in the literature and it remains unclear as to whether
      erythrocytes can utilise extracellular glutathione to enhance the intracellular
      free glutathione pool. We have resolved this issue using a 13C-NMR approach. The
      novel use of L-gamma-glutamyl-L-cysteinyl-[2-13C]glycine allowed the intra- and
      extracellular glutathione pools to be distinguished unequivocally, enabling the
      direct and non-invasive observation over time of the glutathione redox status in
      both compartments. The intracellular glutathione redox status was measured using
      1H spin-echo NMR, while 13C[1H-decoupled] NMR experiments were used to measure
      the extracellular status. Extracellular glutathione was not oxidised in the
      incubations, and did not affect the intracellular glutathione redox status.
      Extracellular glutathione also did not affect erythrocyte glucose metabolism, as
      measured from the lactate-to-pyruvate ratio. The results reported here refute the
      previously attractive hypothesis that, in glucose-starved erythrocytes,
      extracellular GSH can increase intracellular GSH concentrations by releasing
      bound glutathione from mixed disulfides with membrane proteins.

PMID- 15949129
TI  - Reactive oxygen species mediate lethality induced by far-UV in Escherichia coli
      cells.
AB  - The involvement of reactive oxygen species (ROS) in the induction of DNA damage
      to Escherichia coli cells caused by UVC (254 nm) irradiation was studied. We
      verified the expression of the soxS gene induced by UVC (254 nm) and its
      inhibition by sodium azide, a singlet oxygen (1O2) scavenger. Additional results
      showed that a water-soluble carotenoid (norbixin) protects against the lethal
      effects of UVC. These results suggest that UVC radiation can also cause ROS
      mediated lethality.

PMID- 15949130
TI  - Antioxidant activity of thiosulfinates derived from garlic.
AB  - Garlic extract significantly inhibited the oxidation of methyl linoleate in
      homogeneous acetonitrile solution, whereas the antioxidant effect of allicin-free
      garlic extract, prepared by removing allicin by prepared by removing allicin by
      preparative HPLC, was much lower than that of the garlic extract. These results
      suggest that the antioxidant properties are mostly attributed to the presence of
      allicin in the garlic extract. Allicin a major component of the thiosulfinates in
      garlic extract, was found to be effective for inhibiting methyl linoleate
      oxidation, but its efficiency was less than that of alpha-tocopherol. Next, the
      reactivity of allicin toward the peroxyl radical, which is a chain-propagating
      species, was investigated by direct ESR detection. The addition allicin to 2,2'
      azobis(2,4-dimethylvaleronitrile)-peroxyl radical solution caused the signal
      intensity of the peroxyl radical to dose-dependently decrease, indicating that
      allicin is capable of scavenging the the peroxyl radical and acting as an
      antioxidant. Finally, we studied the structure-anioxidant activity relationship
      for thiosulfinates and suggested that the combination of the allyl group (
      CH2CH=CH2) and the -S(O)S- group is necessary for the antioxidant action of
      thiosulfinates in the garlic extract. In addition, one of the two possible
      combinations, -S(O)S-CH2CH=CH2, was found to make a much larger contribution to
      the antioxidant activity of the thiosulfinates than the other, CH2=CH-CH2-S(O)S-.

PMID- 15949131
TI  - Involvement of nitric oxide in neurodegeneration: a study on the experimental
      models of Parkinson's disease.
AB  - The present study was undertaken to explore involvement of nitric oxide (NO) in
      the experimental models of Parkinson's disease. Neurodegeneration was induced by
      unilateral injections of 6-hydroxydopamine (6-OHDA) or lipopolysaccharide (LPS)
      in the right striatum. Lesions were functionally evaluated by amphetamine-induced
      asymmetrical behaviour and by decrease in the tyrosine hydroxylase (TH)
      immunostaining. An induction in the expression of iNOS and augmentation in
      nitrite content was observed in both the models. The extent of increase in iNOS
      expression was, however, different but the elevation in the nitrite content was
      comparable in both the models. The increase in iNOS expression inversely
      correlated with the tyrosine hydroxylase (TH) immunolabeling. Animals pretreated
      with a NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), exhibited
      complete protection against amphetamine induced rotations in both the models.
      Thus, augmented NO availability subsequent to iNOS induction seems to play an
      important role in the initial phase of neurodegeneration.

PMID- 15949133
TI  - Detoxifying endotoxin: time, place and person.
AB  - Animals that cannot sense endotoxin may die if they are infected by Gram-negative
      bacteria. Animals that sense endotoxin and respond too vigorously may also die,
      victims of their own inflammatory reactions. The outcome of Gram-negative
      bacterial infection is thus determined not only by an individual's ability to
      sense endotoxin and respond to its presence, but also by numerous phenomena that
      inactivate endotoxin and/or prevent harmful reactions to it. Endotoxin sensing
      requires the MD-2/TLR4 recognition complex and occurs principally in local
      tissues and the liver. This review highlights the known detoxification
      mechanisms, which include: (i) proteins that facilitate LPS sequestration by
      plasma lipoproteins, prevent interactions between the bioactive lipid A moiety
      and MD-2/TLR4, or promote cellular uptake via non-signaling pathway(s); (ii)
      enzymes that deacylate or dephosphorylate lipid A; (iii) mechanisms that remove
      LPS and Gram-negative bacteria from the bloodstream; and (iv) neuroendocrine
      adaptations that modulate LPS-induced mediator production or neutralize pro
      inflammatory molecules in the circulation. In general, the mechanisms for sensing
      and detoxifying endotoxin seem to be compartmentalized (local versus systemic),
      dynamic, and variable between individuals. They may have evolved to confine
      infection and inflammation to extravascular sites of infection while preventing
      harmful systemic reactions. Integration of endotoxin sensing and detoxification
      is essential for successful host defense.

PMID- 15949134
TI  - Interleukin-18 does not modulate the acute-phase response.
AB  - IL-18 is a pro-inflammatory cytokine of the IL-1 family and it induces IL-1, TNF,
      and IL-6, all of which are endogenous pyrogens. The pyrogenic properties of
      recombinant IL-18 were studied in a rabbit model of fever. rIL-18 did not cause
      fever when injected intravenously into rabbits. Furthermore, the ability of rIL
      18 to modulate other components of the acute-phase response was assessed. rIL-18
      did not induce leukocytosis, or changes of circulating concentrations of
      lipoproteins and corticosterone in mice. In conclusion, rIL-18 is not able to
      induce a febrile response in rabbits and does not modulate the acute-phase
      response in mice.

PMID- 15949135
TI  - Legionella pneumophila mediated activation of dendritic cells involves CD14 and
      TLR2.
AB  - In this study, we analyzed the activation of bone-marrow derived dendritic cells
      (BMDCs) from mice lacking the cd14-gene with purified Legionella pneumophila
      lipopolysaccharide and with viable or formalin-killed L. pneumophila. We found
      that low concentrations of LPS and doses of L. pneumophila that are relevant to
      infection are dependent on CD14 to activate BMDCs. Higher concentrations of LPS
      are able to overcome the lack of CD14 indicating that other receptors
      areinvolved. We, therefore, included studies using BMDCs from mice lacking
      functional TLR2 and/or TLR4 molecules. We found that purified L. pneumophila LPS
      as well as L. pneumophila either viable or formalin-killed are able to activate
      BMDCs from TLR4-deficient C3H/HeJ mice but fail to activate BMDCs from TLR2
      knockout mice. Our data show that not only purified LPS from L. pneumophila but
      also the microorganism itself stimulate BMDCs via TLR2 and that this stimulation
      is dependent on CD14 in this mouse model.

PMID- 15949136
TI  - Apolipoproteins modulate the inflammatory response to lipopolysaccharide.
AB  - An increasing body of evidence demonstrates a close interplay between lipoprotein
      metabolism and sepsis. Sepsis results in an increase of plasma triglycerides
      within VLDL as a consequence of an enhanced hepatic VLDL production and/or
      inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases
      plasma cholesterol within LDL and mainly HDL. The decrease in HDL is accompanied
      by a loss of mainly apoAI-containing particles, an almost total loss of apoCI,
      and an increase in apoE-containing HDL, as related to the effect of LPS on a wide
      range of apolipoproteins, plasma enzymes, lipid transfer factors, and receptors
      that are involved in HDL metabolism. Reciprocally, all lipoprotein classes have
      been shown to bind LPS and to attenuate the biological response to LPS in vitro
      and in rodents. Moreover, triglyceride-rich lipoproteins protect rodents against
      death from LPS and bacterial sepsis. Accumulating evidence indicates that
      apolipoproteins such as apoE and apoAI, and not the lipid moieties of the
      particles, may be responsible for these protective effects of lipoproteins.
      Therefore, to increase our understanding of the complex interaction between
      lipoprotein metabolism and sepsis, further studies that address the specific
      roles of apolipoproteins in sepsis are warranted.

PMID- 15949137
TI  - Structure and metabolism of peptidoglycan and molecular requirements allowing its
      detection by the Drosophila innate immune system.
AB  - Peptidoglycan (murein) is a major essential and specific constituent of the
      bacterial cell wall. Its main function is to protect cells against the internal
      osmotic pressure and to maintain the characteristic cell shape. It also serves as
      a platform for the anchoring of specific proteins and other cell wall components.
      This giant macromolecule is composed of long glycan chains cross-linked by short
      peptides. Any alteration of the disaccharide-peptide basic unit results in a
      global change of peptidoglycan structure and properties. Such global variations
      are encountered in nature as conserved variations along phyletic lines but have
      sometimes been acquired as a result of mutations or as a mechanism of resistance
      against cell-wall targeted antibiotics. During bacterial cell growth and
      division, the peptidoglycan mesh is constantly broken down by a set of highly
      specific hydrolases in a maturation process allowing insertion of newly
      synthesized units in the pre-existing polymerized material. Depending on the
      bacterial species considered, degradation fragments are either released in the
      growth medium or efficiently re-utilized for synthesis of new murein in a
      sequence of events termed the recycling pathway. Peptidoglycan is one of the main
      pathogen-associated molecular patterns recognized by the host innate immune
      system. Variations of the structure and metabolism of this cell wall component
      have been exploited by host defense mechanisms for detection/identification of
      invading bacterial species. Modification of the peptidoglycan structure could
      also represent a mechanism allowing bacteria to escape these host defense
      systems.

PMID- 15949138
TI  - Innate immunity of the human newborn: distinct cytokine responses to LPS and
      other Toll-like receptor agonists.
AB  - Human newborns are at increased risk of microbial invasion and display diminished
      responses to many vaccines indicating a functional immaturity of the immune
      system at birth. Such altered immune reactivity may reflect the demands of in
      utero existence, including the need to avoid potentially harmful inflammatory
      immune reactions. Despite normal basal expression of Toll-like receptors and
      membrane CD14, innate immune responses of neonatal mononuclear cells to
      lipopolysaccharide are characterized by markedly reduced release of the pro
      inflammatory Th1-polarizing cytokines TNF-alpha and interferon-gamma with
      relative preservation of anti-inflammatory Th2-polarizing cytokines. Differences
      between newborns and adults with respect to TLR-induced TNF-alpha release extend
      to a range of TLR agonists, including bacterial lipopeptides, and are due to
      differences in soluble factors present in blood plasma. Soluble factors in
      neonatal blood plasma suppress TLR-induced TNF-alpha release from monocytes and
      efforts to identify and characterize these inhibitors are on-going. Such altered
      immunity to TLR agonists is likely to alter both innate and adaptive immune
      responses in newborns profoundly. Definition of the mechanisms underlying
      distinct neonatal immunity promises to identify novel ways to prevent and treat
      infection in this relatively high-risk population.

PMID- 15949140
TI  - The role of epithelial Toll-like receptor expression in host defense and
      microbial tolerance.
AB  - The recognition of microbial structures by Toll-like receptors (TLRs) on
      professional immune cells situated at sterile internal body sites occurs during
      invasive microbial infection. It indicates infectious non-self and thereby
      represents the adequate co-stimulatory signal to initiate activation of the
      adaptive immune system against the invading pathogen. In contrast, most
      epithelial body surfaces are permanently colonized by microbial organisms of the
      normal flora and thus TLR ligands are present under physiological conditions. In
      the following, we discuss the characteristics of TLR-mediated recognition by
      epithelial cells, the subsequent activation of the host immune system, and
      protective mechanisms that might help to avoid inadequate stimulation and allow
      differentiation between commensal or pathogenic micro-organisms. Recent findings
      suggest that the role of epithelial cells in the maintenance of stable microbial
      colonization of host surfaces and the immediate host response to infectious
      challenges might have to be revised.

PMID- 15949139
TI  - Monomeric endotoxin:protein complexes are essential for TLR4-dependent cell
      activation.
AB  - Potent TLR4-dependent cell activation by Gram-negative bacterial endotoxin
      depends on sequential endotoxin?protein and protein?protein interactions with
      LBP, CD14, MD-2 and TLR4. LBP and CD14 combine, in an albumin-dependent fashion,
      to extract single endotoxin molecules from purified endotoxin aggregates (E(agg))
      or the bacterial outer membrane and form monomeric endotoxin:CD14 complexes that
      are the preferred presentation of endotoxin for transfer to MD-2. Endotoxin in
      endotoxin:CD14is readily transferred to MD-2, again in an albumin-dependent
      manner, to form monomeric endotoxin:MD-2 complex. This monomeric
      endotoxin:protein complex (endotoxin:MD-2) activates TLR4 at picomolar
      concentrations, independently of albumin, and is, therefore, the apparent ligand
      in endotoxin-dependent TLR4 activation. Tetra-, penta-, and hexa-acylated forms
      of meningococcal endotoxin (LOS) react similarly with LBP, CD14, and MD-2 to form
      endotoxin:MD-2 complexes. However, tetra- and penta-acylated LOS:MD-2 complexes
      are less potent TLR4 agonists than hexa-acylated LOS:MD-2. This is mirrored in
      the reduced activity of tetra-, penta- versus hexa-acylated LOS aggregates
      (LOS(agg)) + LBP toward cells containing mCD14, MD-2, and TLR4. Therefore,
      changes in agonist potency of under-acylated meninigococcal LOS are determined by
      differences in properties of monomeric endotoxin:MD-2.

PMID- 15949141
TI  - Editorial.

PMID- 15949142
TI  - Lipopolysaccharide inner core oligosaccharide structure and outer membrane
      stability in human pathogens belonging to the Enterobacteriaceae.
AB  - In the Enterobacteriaceae, the outer membrane is primarily comprised of
      lipopolysaccharides. The lipopolysaccharide molecule is important in mediating
      interactions between the bacterium and its environment and those regions of the
      molecule extending further away from the cell surface show a higher amount of
      structural diversity. The hydrophobic lipid A is highly conserved, due to its
      important role in the structural integrity of the outer membrane. Attached to the
      lipid A region is the core oligosaccharide. The inner core oligosaccharide (lipid
      A proximal) backbone is also well conserved. However, non-stoichiometric
      substitutions of the basic inner core structure lead to structural variation and
      microheterogeneity. These include the addition of negatively charged groups
      (phosphate or galacturonic acid), ethanolamine derivatives, and glycose residues
      (Kdo, rhamnose, galactose, glucosamine, N-acetylglucosamine, heptose, Ko). The
      genetics and biosynthesis of these substitutions is beginning to be elucidated.
      Modification of heptose residues with negatively charged molecules (such as
      phosphate in Escherichia coli and Salmonella and galacturonic acid in Klebsiella
      pneumoniae) has been shown to be involved in maintaining membrane stability.
      However, the biological role(s) of the remaining substitutions is unknown.

PMID- 15949143
TI  - Differential maturation of murine bone-marrow derived dendritic cells with
      lipopolysaccharide and tumor necrosis factor-alpha.
AB  - Dendritic cells (DCs) play a key role in the interface between the innate and
      acquired immune systems. In response to both exogenous as well as endogenous
      signals, DCs undergo a programmed maturation to become an efficient, antigen
      presenting cell. Yet little is known regarding the differential responses by
      endogenous versus exogenous stimuli on DC maturation. In the present report, we
      have compared the phenotypic, functional, and genome-wide expression responses
      associated with maturation by bone marrow derived DCs to either an endogenous
      danger signal, tumor necrosis factor-alpha (TNF-alpha), or a microbial product,
      bacterial lipopolysaccharide (LPS). Examination of the cell surface expression of
      DCs as well as cytokine production demonstrated that patterns of DC maturation
      varied dramatically depending upon the stimulus. Whereas LPS was highly effective
      in terms of inducing phenotypic and functional maturation, TNF-alpha exposure
      produced a phenotypically distinct DC. Gene expression patterns in DCs 6 and 24 h
      after LPS and TNF-alpha exposure revealed that these activation signals produce
      fundamentally different genomic responses. Supervised analysis revealed that the
      expression of 929 probe sets discriminated among the treatment groups, and the
      patterns of gene expression in TNF-alpha stimulated DCs were more similar to
      unstimulated cells at both 6 and 24 h post-stimulation than to LPS-stimulated
      cells at the same time points. These findings reveal that DCs are capable of a
      varying phenotypic response to different antigens and endogenous signals.

PMID- 15949144
TI  - Remodeling of Helicobacter pylori lipopolysaccharide.
AB  - Modification of the lipid A domain of lipopolysaccharide (LPS) has been reported
      to contribute to the virulence and pathogenesis of various Gram-negative
      bacteria. The Kdo (3-deoxy-D-manno-octulosonic acid)-lipid A domain of
      Helicobacter pylori LPS shows several differences to that of Escherichia coli. It
      has fewer acyl chains, a reduced number of phosphate groups, much lower
      immunobiological activity, and only a single Kdo sugar is attached to the
      disaccharide backbone. However, H. pylori synthesizes a minor lipid A species
      resembling that of E. coli, which is both bis-phosphorylated and hexa-acylated
      suggesting that the major species results from the action of specific modifying
      enzymes. This work describes two enzymes, a lipid A phosphatase and a
      phosphoethanolamine transferase, involved in the periplasmic modification of the
      1-position of H. pylori lipid A. Furthermore, we report a novel Kdo trimming
      enzyme that requires prior removal of the 1-phosphate group for enzymatic
      activity. Discovery of the enzymatic machinery involved in the remodeling of H.
      pylori LPS will help unravel the importance of these modifications in H. pylori
      pathogenesis.

PMID- 15949145
TI  - Lipid-mediated resistance of Gram-negative bacteria against various pore-forming
      antimicrobial peptides.
AB  - Lipopolysaccharides (LPSs) play a dual role as target and as effector molecules.
      The knowledge of the LPS-induced activation of human immune cells is increasing;
      however, surprisingly, much less effort seems to be directed towards the
      understanding of the mechanisms leading to the killing of the bacterial
      organisms, which eventually results in the release of LPS from the bacterial
      surface into the blood circulation. We demonstrate mechanisms of interaction of
      peptides of the innate immune system (e.g. defensins and cathelicidins) as well
      as of externally administered antibiotics (e.g. Polymyxin B) with Gram-negative
      bacteria. The main focus is directed on data derived from electrical measurements
      on a reconstitution system of the outer membrane as an asymmetric bilayer
      composed on one side of LPS and on the other of phospholipids. All these
      antimicrobial peptides (AMPs) are membrane-active and induce the permeabilization
      of the reconstituted membranes by the formation of lesions. We found that
      differences in the activity of the AMPs against various sensitive and resistant
      Gram-negative bacteria can be explained solely by variations in the chemical
      structure of LPS, e.g. in the composition of the sugar head group. A reduction of
      the net negative charge of LPS is responsible for a reduced interaction with the
      polycationic AMPs and thus for resistance. A most important side effect of
      positively charged AMPs is the neutralization of the negatively charged LPS
      released from the bacterial surface as a consequence of AMP-induced killing.

PMID- 15949146
TI  - Role of lipid A palmitoylation in bacterial pathogenesis.
AB  - The presence of palmitate in a minor fraction of lipid A has been known since the
      chemical structure of lipid A was first elucidated, but the functional importance
      in bacterial pathogenesis of regulated lipid A palmitoylation has become clear
      only recently. A palmitate chain from a phospholipid is incorporated into lipid A
      by an outer membrane enzyme PagP. The isolation of pagP mutants from pathogenic
      Gram-negative bacteria has revealed that palmitoylated lipid A can both protect
      the bacterium from certain host immune defenses and attenuate the ability of
      lipid A to activate those same defenses through the TLR4 signal transduction
      pathway. The mechanisms by which bacteria regulate the incorporation of palmitate
      into lipid A strikingly reflect the corresponding organism's pathogenic
      lifestyle. Variations on these themes can be illustrated with the known pagP
      homologs from Gram-negative bacteria, which include pathogens of humans and other
      mammals in addition to pathogens of insects and plants. The PagP enzyme is now
      lending itself both as a target for the development of anti-infective agents, and
      as a tool for the synthesis of lipid A-based vaccine adjuvants and endotoxin
      antagonists.

PMID- 15949147
TI  - Interactions between LPS and lung surfactant proteins.
AB  - After penetration into the lower airways, bacterial lipopolysaccharide (LPS)
      interacts with alveolar cells in a fluid environment consisting of pulmonary
      surfactant, a lipid-protein complex which prevents alveolar collapsing and
      participates in lung defense. The two hydrophilic surfactant components SP-A and
      SP-D are proteins with collagen-like and lectin domains (collectins) able to
      interact with carbohydrate-containing ligands present on microbial membranes, and
      with defined regions of LPS. This explains their capacity to damage the bacterial
      envelope and induce an antimicrobial effect. In addition, they modulate LPS
      induced production of pro-inflammatory mediators in leukocytes by interaction
      with LPS or with leukocyte receptors. A third surfactant component, SP-C, is a
      small, highly hydrophobic lipopeptide which interacts with lipid A and reduces
      LPS-induced effects in macrophages and splenocyte cultures. The interaction of
      the different SPs with CD14 might explain their ability to modulate some LPS
      responses. Although the alveolar fluid contains other antiLPS and antimicrobial
      agents, SPs are the most abundant proteins which might contribute to protect the
      lung epithelium and reduce the incidence of LPS-induced lung injury. The presence
      of the surfactant collectins SP-A and SP-D in non-pulmonary tissues, such as the
      female genital tract, extends their field of action to other mucosal surfaces.

PMID- 15949148
TI  - MD-2 and Der p 2 - a tale of two cousins or distant relatives?
AB  - MD-2, an LPS-binding protein is essential for the recognition of LPS by TLR4. MD
      2 belongs to the ML superfamily of lipid-binding proteins. The tertiary structure
      of mite allergen protein Der p 2 was identified as having the protein fold most
      compatible with the sequence of MD-2. Comparison of MD-2 and Der p 2 reveals that
      they have many common biochemical characteristics: they are both rich in beta
      structure and they are both very stable proteins as they both unfold only above
      90 degrees C. In Der p 2, six cysteine residues form three disulfide bridges. We
      determined one free cysteine residue per recombinant biologically active MD-2
      molecule, supporting similar disulfide topology with three disulfides bridges as
      in Der p 2. MD-2 binds LPS with high affinity; however, only weak binding of LPS
      was detected with Der p 2. Comparison of electrostatic potentials of the
      structural model of MD-2 and Der p 2 indicates a region of high positive
      potential on MD-2 and its absence in Der p 2, which may be the reason for its
      weak binding of LPS. We suggest that Der p 2 and its homologues probably do not
      have a role in response to Gram-negative bacteria in insects and that MD-2 family
      members with their specific role in innate immunity probably evolved from an ML
      ancestor only in higher vertebrates.

PMID- 15949149
TI  - HbA1c or glucose for diabetes diagnosis?

PMID- 15949150
TI  - Liver enzymes, fatty liver and type 2 diabetes.

PMID- 15949151
TI  - The British Society of Gastroenterology guidelines for the investigation of
      chronic diarrhoea, 2nd edition.
AB  - The prevalence of chronic diarrhoea has been estimated at 4-5% in Western
      populations and is one of the most common reasons for referral to a
      gastroenterological clinic. Investigation of patients was rationalized in 2003
      with the publication by the British Society of Gastroenterology of guidelines for
      the investigation of chronic diarrhoea. The guidelines may also be viewed at
      www.bsg.org.uk/clinical_prac/guidelines/chronic_diarr.htm.

PMID- 15949152
TI  - Macroprolactin; high molecular mass forms of circulating prolactin.
AB  - Two high molecular mass forms of prolactin (PRL) in serum have been identified by
      gel filtration chromatography (GFC): macroprolactin (big-big PRL, > 100 kDa) and
      big PRL (40-60 kDa). Macroprolactin has a variable composition and structure, but
      is most frequently a complex of PRL and IgG, with a molecular mass of 150-170
      kDa. It is formed in the circulation following pituitary secretion of monomeric
      PRL but has a longer half-life, and the PRL in the complex remains reactive to a
      variable extent in immunoassays. In the majority of subjects little or no
      macroprolactin can be detected in serum, but in some individuals it may be the
      predominant immunoreactive component of circulating PRL and the cause of apparent
      hyperprolactinaemia. Owing to its high molecular mass, macroprolactin appears to
      be confined to the intravascular compartment and much evidence indicates that it
      has minimal bioactivity in vivo and is not of pathological significance.
      Nevertheless, hyperprolactinaemia due to macroprolactin can lead to diagnostic
      confusion and unnecessary further investigation and treatment if it is not
      recognized as such. Macroprolactin is a common cause of apparent
      hyperprolactinaemia with some assays and it is essential that laboratories
      introduce screening programmes to examine samples with elevated total
      immunoreactive PRL for the presence of macroprolactin and determine the monomeric
      PRL component which is known to be bioactive in vivo. A number of screening tests
      have been described; that based on the precipitation of macroprolactin with
      polyethylene glycol has been the most widely validated and applied. The reference
      technique of GFC should be available for confirmation and further investigation
      of samples, giving equivocal results in screening tests. In comparison with
      macroprolactin, little is known about big PRL. It is a more consistent component
      of total serum PRL but rarely, if ever, the cause of hyperprolactinaemia. Further
      research is required into the nature of macroprolactin and big PRL, the
      relationships between high molecular mass forms of PRL, and their clinical
      significance.

PMID- 15949153
TI  - HbA1c predicts the likelihood of having impaired glucose tolerance in high-risk
      patients with normal fasting plasma glucose.
AB  - BACKGROUND: Although the oral glucose tolerance test (OGTT) is the 'gold
      standard' for diagnosing prediabetes/diabetes, it is inconvenient for the patient
      and time consuming. The only alternative simple screening test is fasting plasma
      glucose (FPG). FPG concentrations of > 6.0 mmol/L represent prediabetes/diabetes.
      FPG concentrations of < or = 6.0 mmol/L may be considered 'normal', although some
      such patients will demonstrate abnormal glucose tolerance when subjected to an
      OGTT. We have evaluated the use of glycated haemoglobin (HbA1c) as a screening
      test for diabetes or impaired glucose tolerance (IGT) in patients who have risk
      factors for diabetes but FPG < or = 6.0 mmol/L. METHODS AND RESULTS: A total of
      580 patients with at least two risk factors for diabetes underwent an OGTT and
      HbA1c measurement. In all, 225 patients had a FPG < or = 6.0 mmol/L and met the
      inclusion criteria. Of these, 23.1% (n=52) had an abnormal OGTT result (45 had
      IGT and 7 had diabetes). Subjects with abnormal glucose tolerance had a higher
      percentage of HbA1c than subjects with normal glucose tolerance (P<0.001). An
      HbA1c of 5.6% gave an optimal sensitivity of 72% and specificity of 77% to
      predict a 2 h plasma glucose > or = 7.8 mmol/L. CONCLUSION: The use of FPG
      concentration followed by selective measurement of HbA1c in patients who are at
      high risk of developing diabetes may represent a reasonable approach to
      identifying patients requiring an OGTT.

PMID- 15949154
TI  - Establishing a practical blood platelet threshold to avoid reporting spurious
      potassium results due to thrombocytosis.
AB  - BACKGROUND: Thrombocytosis is one of several pre-analytical factors which
      contribute to spuriously high serum potassium concentrations, yet there is little
      published data to guide analysts in the selection of a specific platelet count
      threshold above which serum potassium results become unreliable. We have studied
      the sensitivity and specificity of blood platelet count as a predictor of false
      elevations in potassium. METHODS: Paired serum and plasma potassium measurements
      together with full blood count were performed for 300 patients. All samples were
      stored at room temperature and analysed within 4 h of collection. The difference
      between serum and plasma potassium was plotted against blood platelet count.
      RESULTS: When the difference (serum-plasma) in potassium concentration was
      plotted against platelet count, there was a direct linear relationship. Blood
      platelet counts of >500 x 10(9)/L will detect elevations in serum relative to
      plasma potassium of >0.5 mmol/L, with a sensitivity of 71% and a specificity of
      89%. CONCLUSION: It is recommended that where blood platelet count is above 500 x
      10(9)/L, potassium measurements should be repeated using lithium heparin plasma.
      When serum potassium results of >5.4 mmol/L are obtained, it is our policy to
      check the platelet count if a sample is available before reporting results. If
      available and above 500 x 10(9)/L, potassium results are withheld and plasma
      requested.

PMID- 15949155
TI  - Elevated urinary dopamine in adults and children.
AB  - BACKGROUND: Information on the significance of an elevated urinary dopamine is
      limited and can lead to misinterpretation of the cause of such a finding. This
      laboratory-based study examines the associations with elevated dopamine gathered
      from a significant number of patients. METHODS: The urine catecholamine and
      metabolite results of specimens (analysed by HPLC-ECD) from 5933 adults and 467
      children were examined retrospectively over a 57-month period. Those with
      elevated dopamine were identified and the explanation for this finding was
      sought. RESULTS: In adults, the conditions associated with an elevated dopamine
      were: urine over-collection; drug effects (including those due to intravenous
      dopamine, L-dopa, methyldopa, clozapine, antidepressants and metoclopramide);
      clinical effects (including those due to phaeochromocytoma, carcinoid tumour and
      pregnancy). In children, high urine dopamine was found in cases of neuroblastoma,
      Costello syndrome, leukaemia, phaeochromocytoma, Menkes disease and
      rhabdomyosarcoma of the bladder. CONCLUSIONS: A high urine dopamine was found in
      <3% of adult urine specimens. It was most commonly associated with: over
      collection, probable drug effects and neural crest tumours. Neuroblastoma was the
      most common cause of elevated dopamine in children's specimens, although other
      associations are described. Some await explanation.

PMID- 15949156
TI  - An innovative Australian point-of-care model for urine albumin: creatinine ratio
      testing that supports diabetes management in indigenous medical services and has
      international application.
AB  - BACKGROUND: Type 2 diabetes is the leading cause of end-stage renal failure in
      Australia's indigenous people. The measurement of urine albumin:creatinine ratio
      (ACR) as a marker for early renal disease is an important component of the
      management of indigenous patients with diabetes. METHODS: An innovative national
      program (Quality Assurance for Aboriginal Medical Services [QAAMS]) for point-of
      care (POC) urine ACR testing on the DCA 2000 analyser (Bayer Diagnostics) was
      established to monitor microalbuminuria in indigenous people with diabetes in 30
      Aboriginal and Torres Strait Islander medical services across Australia.
      Aboriginal health workers perform the ACR test. The QAAMS model provides ongoing
      education and training, an annual workshop, monthly quality assurance testing and
      a telephone help hotline. Quality assurance testing is conducted using paired,
      linearly related samples with a wide range of ACR concentrations (1-25 mg/mmol).
      RESULTS: The average participation rate across four six-monthly QAAMS ACR testing
      cycles was 83%. In all, 94% of 1163 quality assurance tests performed were within
      the preset limits of acceptability. The median precision (coefficient of
      variation percent for ACR quality assurance testing averaged 5.4%, well within
      desirable performance specifications. Between-site accuracy was excellent.
      CONCLUSION: This unique POC model for supporting diabetes management is the first
      of its type to be developed for indigenous communities and has considerable
      potential to be adopted worldwide.

PMID- 15949157
TI  - The cytochrome P450 CYP1A2 genetic polymorphisms *1F and *1D do not affect
      clozapine clearance in a group of schizophrenic patients.
AB  - BACKGROUND: The atypical antipsychotic drug clozapine is metabolized by CYP1A2.
      The activity of CYP1A2 is highly variable and is among others dependent on
      smoking habits. Certain genotypes of CYP1A2 have been associated with increased
      inducibility/activity of CYP1A2. However, the relevance of genotyping for these
      mutations in a clinical setting has not yet been demonstrated. METHODS: In this
      study, the CYP1A2 *1F, *1C and *1D genotypes of 58 schizophrenic patients on
      clozapine treatment were correlated with clozapine serum concentrations corrected
      for dose and weight or concentration/dosage ratios. RESULTS: The allele frequency
      of *1F and *1D was 67% and 6%, respectively. With an allele frequency of 1%, the
      occurrence of *1C was very low. Multivariate analysis of variance did not reveal
      any significant correlations between CYP1A2 genotypes and clozapine clearance in
      these subjects, although a possible effect of the *1D allele cannot be excluded
      in this study. CONCLUSION: Although this study was performed using samples from a
      limited number of patients, routine genotyping of CYP1A2 *1F, *1C or *1D
      polymorphisms for their effect on metabolic capacity is, at least in Caucasians,
      not yet indicated.

PMID- 15949159
TI  - A simple method for the analysis of urinary sucralose for use in tests of
      intestinal permeability.
AB  - BACKGROUND: Sucralose is a unique disaccharide probe which is stable in the colon
      and can be used to assess permeability over the whole gut. Additional information
      can be gained when sucralose is administered in combination with lactulose and a
      monosaccharide such as L-rhamnose in the form of a 'triple sugar test.' We
      describe a simple assay for urinary sucralose by HPLC with refractive index
      detection (HPLC-RI). METHODS: Phenyl-beta-D-glucopyranoside (internal standard)
      was added to 10 mL of urine, which was then passed through a 0.45 microm syringe
      filter. Elution was with 30% methanol (1 mL/min) on a reverse-phase C18 column.
      Detection was by refractive index, and integration based upon peak areas. Sixty
      standards of sucralose in human urine were analysed in order to quantify
      analytical variation. RESULTS: The standard curve for urinary sucralose was
      linear from 25 to 500 mg/L (r>0.99). The limit of detection was 11 mg/L.
      Analytical recovery of sucralose at concentrations of 25, 50 and 100 mg/L was
      101.5% (CV 7.59%), 102.9% (CV 5.82%) and 105.0% (CV 4.26%), respectively.
      CONCLUSIONS: The technique described represents a simple assay for urinary
      sucralose which performed with acceptable accuracy and precision and should
      facilitate the use of the triple sugar test in clinical research.

PMID- 15949158
TI  - Effects of menopause and tibolone on antioxidants in postmenopausal women.
AB  - BACKGROUND: Oxidative stress has been implicated in the pathogenesis of ageing
      and menopause, and can arise through the increased production of lipid peroxides
      and/or a deficiency of antioxidant defence. AIM: To investigate the effects of
      the menopause and tibolone treatment (2.5 mg/day for six months) on plasma
      antioxidants and lipid peroxidation. METHODS: Plasma concentrations of ascorbic
      acid, alpha-tocopherol, total thiol groups, caeruloplasmin, erythrocyte
      glutathione (GSH) and malondialdehyde (MDA) were measured in 24 postmenopausal
      and 24 premenopausal healthy women. RESULTS: Data analysis indicates a
      significant decrease in plasma ascorbic acid, alpha-tocopherol, total thiol
      groups, [corrected]erythrocyte GSH and a significant increase in lipid peroxides
      (expressed as MDA concentrations) in postmenopausal women. There was no
      significant difference between control and study groups in the mean plasma
      caeruloplasmin concentrations. It was found that there is a significant increase
      in alpha-tocopherol and significant decrease in lipid peroxide concentrations in
      postmenopausal after tibolone treatment. CONCLUSIONS: The menopause is associated
      with an increase in oxidative stress and a decrease of some antioxidants, such as
      ascorbic acid, alpha-tocopherol, total thiols and erythrocyte GSH. Tibolone
      treatment leads to a decrease in concentrations of plasma lipid peroxide,
      probably by stimulating direct and indirect mechanisms of tocopherol regeneration
      and increasing plasma concentrations of vitamin E. However, due to the relatively
      small numbers involved this study can be regarded as a pilot. Further studies
      performed on a larger scale are necessary to establish the exact mechanisms of
      tibolone in inhibiting oxidative stress in postmenopausal women.

PMID- 15949160
TI  - Acquired copper deficiency following prolonged jejunostomy feeds.
AB  - A 19-year-old man who developed extensive oesophageal lye (Alkali) stricture and
      received long-term enteral nutrition (eight months) with a jejunostomy tube
      developed macrocytic anaemia (Hb: 41 g/L) with leucopenia (white blood cell
      [WBC]: 3.0 x 10(9)/L). The patient's serum vitamin B12, folate, iron and liver
      function tests were normal. Bone marrow examination revealed gross erythroid
      hyperplasia and cytoplasmic vacuolization of erythroid and myeloid elements.
      Further investigations revealed low serum copper (0.3 micromol/L) and
      ceruloplasmin concentrations (<30 mg/L) with marginally low normal serum
      concentration of red cell peroxidase (13 U/gHb), establishing the diagnosis of
      copper deficiency anaemia. The anaemia and leucopenia responded intermittently to
      intravenous copper therapy, but the serum copper concentration dropped when
      intravenous copper therapy was withdrawn. Enteral jejunostomy copper
      supplementation failed to maintain adequate serum copper concentrations. After
      stabilizing the general condition of the patient, a pharyngo-gastric anastamosis
      was performed and normal oral diet commenced, which restored normal serum copper
      concentration. This case report suggests that copper supplements in the form of
      copper sulphate are not adequately absorbed when administered through a
      jejunostomy tube.

PMID- 15949161
TI  - Gitelman's syndrome presenting as intolerance to statin therapy.
AB  - Several factors predisposing patients to statin-induced myopathy have been
      described. We describe a patient whose statin intolerance was associated with
      changes in serum potassium arising from previously undiagnosed Gitelman's
      syndrome.

PMID- 15949162
TI  - Green-coloured results on guaiac-based faecal occult blood testing should be
      considered positive.

PMID- 15949163
TI  - Green-coloured results on guaiac-based faecal occult blood testing.

PMID- 15949164
TI  - Evaluation of the Elecsys NTproBNP assay.

PMID- 15949169
TI  - Health and medical informatics in the 21st century: will the future be about
      E(b)M2C?

PMID- 15949165
TI  - Estimated GFR.

PMID- 15949170
TI  - Identifying and establishing consensus on the most important safety features of
      GP computer systems: e-Delphi study.
AB  - Our objective was to identify and establish consensus on the most important
      safety features of GP computer systems, with a particular emphasis on medicines
      management. We used a two-round electronic Delphi survey, completed by a 21
      member multidisciplinary expert panel, all from the UK. The main outcome measure
      was percentage agreement of the panel members on the importance of the presence
      of a number of different safety features (presented as clinical statements) on GP
      computer systems. We found 90% or greater agreement on the importance of 32 (58%)
      statements. These statements, indicating issues considered to be of considerable
      importance (rated as important or very important), related to: computerised
      alerts; the need to avoid spurious alerts; making it difficult to override
      critical alerts; having audit trails of such overrides; support for safe repeat
      prescribing; effective computer-user interface; importance of call and recall
      management; and the need to be able to run safety reports. The high level of
      agreement among the expert panel members indicates clear themes and priorities
      that need to be addressed in any further improvement of safety features in
      primary care computing systems.

PMID- 15949171
TI  - Communicating about medications during primary care outpatient visits: the role
      of electronic medical records.
AB  - OBJECTIVES: To assess the role of electronic medical records (EMR) in
      facilitating the content and process of patient-provider exchanges about
      medications during outpatient primary care visits. METHODS: Fifty encounters with
      six physicians using the EMR were videotaped, transcribed and content-analysed by
      applying conversation analysis and ethnomethodology techniques. The analysis
      focused on three aspects of medication communication: (1) process of care:
      practices by patients and physicians to implement medication decisions; (2)
      themes: medication topics that consistently emerge; and (3) names: ways patients
      and physicians refer to medications. In-depth analysis of 20 encounters examined
      the extent to which either or both parties initiated, expanded and concluded
      medication discussions. RESULTS: On average 21.2 (range: 8-35; SD=7.4) distinct
      exchanges per encounter were observed. Of those, 33% were related to medication.
      Of the 350 medication-related exchanges throughout the encounters, 56% were
      categorised as routine medication discussion such as ordering and/or refilling
      medications. Mailing issues were the next most common medication-related
      exchanges (10.6%), followed by partial adherence (8.9%), self-regulation (7.4%),
      alternative therapy/over-the-counter medication (6.6%), side effects (6%) and
      formulary issues (4.6%). Patients and providers used three ways to name
      medications: generic/scientific name (42%); physical description (39.7%) and
      brand name (18.3%). Forty-one percent of exchanges included initiation by one or
      both parties but no further discussion of the issue; 42% included initiation and
      expansion by both parties but not conclusion; only 17% of exchanges contained
      complete medication exchanges (initiation, expansion and conclusion) by both
      parties. CONCLUSIONS: EMR facilitated content and process of communication
      regarding medications during outpatient encounters, especially among patients
      taking multiple medications and patients who used physical descriptions to
      identify their medications. EMR use stimulated medication exchanges, leading to
      further expansion about the topic. However, fewer than one-fifth of exchanges
      ended with clear conclusions by both parties regarding prescribed medication
      regimens.

PMID- 15949172
TI  - Application of fuzzy classification in modern primary dental care.
AB  - This paper describes a framework for implementing fuzzy classifications in
      primary dental care services. Dental practices aim to provide the highest quality
      services for their patients. To achieve this, it is important that dentists are
      able to obtain patients' opinions about their experiences in the dental practice
      and are able to accurately evaluate this. We propose the use of fuzzy
      classification to combine various assessment criteria into one general measure to
      assess patients' satisfaction with primary dental care services. The proposed
      framework can be used in conventional dental practice information systems and
      easily integrated with those already used. The benefits of using the proposed
      fuzzy classification approach include more flexible and accurate analysis of
      patients' feedback, combining verbal and numeric data. To confirm our theory, a
      prototype was developed based on the Microsoft SQL Server database management
      system for two criteria used in dental practices, namely making an appointment
      with a dentist and waiting time for dental care services.

PMID- 15949173
TI  - Design and development of a web-based application for diabetes patient data
      management.
AB  - A web-based database management system developed for collecting, managing and
      analysing information of diabetes patients is described here. It is a searchable,
      client-server, relational database application, developed on the Windows platform
      using Oracle, Active Server Pages (ASP), Visual Basic Script (VB Script) and Java
      Script. The software is menu-driven and allows authorized healthcare providers to
      access, enter, update and analyse patient information. Graphical representation
      of data can be generated by the system using bar charts and pie charts. An
      interactive web interface allows users to query the database and generate
      reports. Alpha- and beta-testing of the system was carried out and the system at
      present holds records of 500 diabetes patients and is found useful in diagnosis
      and treatment. In addition to providing patient data on a continuous basis in a
      simple format, the system is used in population and comparative analysis. It has
      proved to be of significant advantage to the healthcare provider as compared to
      the paper-based system.

PMID- 15949174
TI  - Web-based health applications provide useful and cost-effective tools; however,
      they should include key clinical variables and incorporate a coding or
      classification system.

PMID- 15949175
TI  - Multi-ontology sense making: a new simplicity in decision making.
AB  - Imagine organising a birthday party for a group of young children. Would you
      agree a set of learning objectives with their parents in advance of the party?
      Would those objectives be aligned with the mission statement for education in the
      society to which you belong? Would you create a project plan for the party with
      clear milestones associated with empirical measures of achievement? Would you
      start the party with a motivational video so that the children did not waste time
      in play not aligned with the learning objectives? Would you use PowerPoint to
      demonstrate to the children that their pocket money is linked to achievement of
      the empirical measures at each milestone? Would you conduct an after-action
      review at the end of the party, update your best practice database and revise
      standard operating procedures for party management? No! Instead, like most
      parents, you would create barriers to prevent certain types of behaviour, you
      would use attractors (party games, a football, a videotape) to encourage the
      formation of beneficial largely self-organising identities; you would disrupt
      negative patterns early, to prevent the party becoming chaotic, or necessitating
      the draconian imposition of authority. At the end of the party you would know
      whether it had been a success, but you could not have defined (in other than the
      most general terms) what that success would look like in advance.

PMID- 15949176
TI  - Potential impacts of patient access to their electronic care records.
AB  - This paper examines the interest and expectations of patients having access to
      their electronic care records. Semi-structured prospective interviews were
      performed with 109 patients in a community setting in London where all records
      are stored digitally either as coded data, free text or scanned in from the paper
      original. A booth had recently been set up for patients to access their
      electronic records in the waiting room with secure access through fingerprint
      recognition technology. The interviews detailed history and levels of interest in
      access, impact on relationship with clinician, familiarity with digital media and
      issues of security and accuracy. Patients were more interested in seeing their
      electronic than their paper record; they felt it would improve their relationship
      with their clinician; they generally trusted in the security of their records;
      they anticipated that there would be some mistakes; they were enthusiastic about
      the idea of adding to the record themselves, but were divided about having access
      over the internet. Patients are confident in and anticipate the value of having
      access to their electronic records.

PMID- 15949177
TI  - Bringing SNOMED-CT into use within primary care.

PMID- 15949178
TI  - Codes, classifications, terminologies and nomenclatures: definition, development
      and application in practice.
AB  - The Primary Care Informatics Working Group of EFMI is working to help develop the
      core theory of primary care informatics (PCI). Codes, classifications,
      terminologies and nomenclatures form an important part of the science of PCI, as
      they allow clinical information to be readily stored and processed in information
      systems. This article provides definitions and a history of the International
      Classification for Primary Care (ICPC), and of the Read code and the Systematized
      Nomenclature for Medicine (SNOMED). The Working Group wishes to encourage shared
      definitions and an understanding of the practical application of structured data
      to improve quality in clinical practice.

PMID- 15949181
TI  - Submicroscopic Plasmodium falciparum infections during pregnancy, in an area of
      Sudan with a low intensity of malaria transmission.
AB  - There are few published studies on the burden of malaria during pregnancy from
      areas of sub-Saharan Africa where the intensity of malarial transmission is low,
      and few on submicroscopic malarial infections in pregnant women. The present
      study was conducted in New Halfa, an area of low-intensity transmission in
      eastern Sudan, between August 2003 and July 2004. The main aims were to assess
      the prevalences of submicroscopic and multiple Plasmodium falciparum infections
      in pregnant women (using the P. falciparum merozoite surface protein-2 as a
      polymorphic marker in PCR-based assays) and to determine the effects of such
      infections on anaemia during pregnancy. Of the 142 pregnant women who were
      recruited, only 17 (11.9%) were found smear-positive for P. falciparum by
      microscopy. The results of the PCR-based assays revealed, however, that 40 (32%)
      of the 125 smear-negative women had submicroscopic P. falciparum infections.
      Blood samples from 32 (80%) of those with submicroscopic infections showed only
      the FC 27 allele (of merozoite surface protein-2), six (15%) showed only the ICI
      allele, and two (5%) showed both of these alleles. Although the age, parity,
      gestational age and haemoglobin concentrations of the women with submicroscopic
      P. falciparum infections were not significantly different from those of the women
      who were smear- and PCR-negative, such infections may have a significant impact
      on materno-foetal health.

PMID- 15949180
TI  - Predictors of the failure of treatment with chloroquine plus chlorpheniramine, in
      children with acute, uncomplicated, Plasmodium falciparum malaria.
AB  - Resistance to chloroquine in Plasmodium falciparum can be reversed, both in vitro
      and in vivo, by chlorpheniramine, a histamine H(1) receptor antagonist. This
      reversal raises the possibility of using chlorpheniramine to prolong the clinical
      usefulness of chloroquine in resource-poor communities. The factors that identify
      children at risk of treatment failure after being given chloroquine plus
      chlorpheniramine have now been evaluated in 281 children with uncomplicated, P.
      falciparum malaria. The children, who had taken part in six trials of
      antimalarial drugs between February 1996 and September 1999, in a hyper-endemic
      area of south-western Nigeria, were enrolled prospectively for the present study.
      Following treatment with chloroquine plus chlorpheniramine, 13 (5%) of the
      children failed treatment by day 7 or 14. In a multivariate analysis, an age of <
      or =3 years (adjusted odds ratio = 11.1; 95% confidence interval = 2.2-55.3; P =
      0.003) and a parasitaemia that took >3 days to clear (adjusted odds ratio=7.9;
      95% confidence interval = 1.3-49.4; P = 0.027) were found to be independent
      predictors of treatment failure. In addition, compared with the children who had
      a lower axillary temperature then, the children who had an axillary temperature
      of > or =38 degrees C 2 days after commencing treatment were significantly more
      likely to be treatment failures. In resource-poor communities using chloroquine
      plus chlorpheniramine, the easily identifiable predictors of treatment failure
      might be used to identify children requiring alternative antimalarial drugs.

PMID- 15949182
TI  - Antimalarial activities and toxicities of three plants used as traditional
      remedies for malaria in the Democratic Republic of Congo: Croton mubango ,
      Nauclea pobeguinii and Pyrenacantha staudtii.
AB  - The antimalarial activities of crude extracts and 17 fractions from the partition
      of 80%-methanolic extracts of three plants (the stem bark of Croton mubango, the
      stem bark of Nauclea pobeguinii and the leaves of Pyrenacantha staudtii) used as
      antimalarial remedies in the Democratic Republic of Congo were studied both in
      vitro (against Plasmodium falciparum) and in mice infected with Pl. berghei
      berghei. The toxic effects of dried aqueous extracts of the plants were also
      investigated, in uninfected mice. The most active crude extracts in vitro, with
      median inhibitory concentrations (IC(50)) of <1 microg/ml, were found to be the
      methanolic and dichloromethane extracts of C. mubango, and the dichloromethane
      extracts of N. pobeguinii and Py. staudtii. The aqueous extract with the most
      antimalarial activity in vitro was that of C. mubango (IC(50) = 3.2 microg/ml),
      followed by that of N. probeguinii (IC(50) = 5.3 microg/ml) and then that of Py.
      staudii (IC(50) = 15.2 microg/ml). Results from the in-vivo tests of antimalarial
      activity showed that, at a daily oral dose of 200 mg/kg, all the dichloromethane
      extracts, the petroleum-ether, chloroformic, ethyl-acetate and residual water
      soluble fractions from C. mubango, and the chloroformic, ethyl-acetate and n
      butanolic fractions from Py. staudtii produced >80% chemosuppression of the
      parasitaemias by day 4. The aqueous extracts of C. mubango and N. probeguinii
      produced a slightly lower but still significant inhibition of parasitaemia (60%
      80%) whereas that of Py. staudtii only suppressed the day-4 parasitaemias by 37%.
      The dried aqueous extract of the stem bark of C. mubango showed some signs of
      toxicity in mice, with median lethal doses (LD(50)) of 350 mg/kg in the female
      mice and 900 mg/kg in the male. The extract significantly increased the serum
      concentrations of glutamate-oxaloacetate transaminase (GOT) and glutamate
      pyruvate transaminase (GPT) in mice of both sexes, but had no effect on the blood
      levels of creatinine or urea. No significant toxic effect was observed for the
      dried aqueous extracts of N. pobeguinii and Py. staudtii (LD(50) >5 g/kg).
      Neither of these extracts affected the serum concentrations of GPT or the blood
      concentrations of creatinine and urea, although the N. pobeguinii extract did
      increase the serum concentration of GOT.

PMID- 15949183
TI  - The detection and PCR-based characterization of the parasites causing
      trypanosomiasis in water-buffalo herds in Venezuela.
AB  - The usefulness of PCR-based assays for detecting trypanosomiasis in water
      buffaloes and other livestock was explored, under field conditions, in Venezuela.
      The sensitivity and specificity of the assays, which were based on established
      primer pairs (21-mer/22-mer and ILO1264/ILO1265), were evaluated, partly by
      comparison with the results of parasitological tests (stained bloodsmears and
      microhaematocrit centrifugation) and immunological assays (IFAT) run in parallel.
      The optimised PCR-based assays showed a sensitivity of 10 pg DNA. The use of the
      21-mer/22-mer primer pair gave a test that was specific for species in the
      subgenus Trypanozoon (including Trypanosoma evansi), whereas use of
      ILO1264/ILO1265 produced a test that was specific for T. vivax. The results of a
      hybridization assay using T. evansi-DNA and T. vivax-DNA probes indicated no
      cross-hybridization between the T. evansi and T. vivax PCR products.The results
      of the bloodsmear examinations, microhaematocrit centrifugations (MHC) and IFAT
      indicated that 23 (6.7%), 39 (11.4%) and 135 (39.5%) of the 342 blood samples
      investigated (including 316 from water buffaloes) contained trypanosomes,
      respectively. The results of the PCR-based assays indicated that 68 (19.9%) of
      the same blood samples contained T. vivax (or at least T. vivax DNA), and that
      none contained T. evansi or any other member of the subgenus Trypanozoon. For the
      detection of trypanosomes, the assay therefore appeared almost twice as sensitive
      as the MHC. These results are the first on the molecular characterization of the
      trypanosomes infecting water buffaloes in Venezuela. When the results of the MHC
      (which is the most practical, and frequently used, alternative detection method)
      were used as the gold standard, the PCR-based assay for T. vivax was found to
      have 100% sensitivity, 90.4% specificity, a positive predictive value of 0.57, a
      positive likelihood ratio of 10.45, and a negative likelihood ratio of 0.00. The
      assay therefore appears a reasonable choice for detecting T. vivax in the
      mammalian livestock of Venezuela and elsewhere.

PMID- 15949184
TI  - Evaluation of a dot-immunoblot assay for detecting leishmanial antigen in
      naturally infected Phlebotomus argentipes (Diptera: Psychodidae).
AB  - A simple and highly reproducible dot-immunoblot assay was developed to detect
      leishmanial antigen in Phlebotomus argentipes that were naturally infected with
      Leishmania donovani. The test was sensitive to as little as 10 ng of antigenic
      protein (equivalent to the gut content of one laboratory-infected sandfly) and
      also appeared to be specific, in that it gave a positive result with some P.
      argentipes (the primary vector of L. donovani in India) and L. donovani but not
      with P. papatasi or other pathogens. When used to investigate a large number of
      sandflies collected from two areas of the Indian state of Bihar where visceral
      leishmaniasis is endemic, the assay appeared sufficiently sensitive and specific
      to detect the naturally infected insects. The simplicity, reproducibility, high
      sensitivity and high specificity of the assay should make it useful for field
      studies, particularly in determining the prevalence of sandfly infection, the
      local level of transmission, and the impact of vector-control programmes.

PMID- 15949185
TI  - Preliminary characterisation of Toxoplasma gondii isolates from Zimbabwe, with
      stage-specific monoclonal antibodies.
AB  - Cell-culture-derived clones of eight Toxoplasma gondii isolates from Zimbabwe
      were characterised in IFAT with a panel of five monoclonal antibodies (mAb). Each
      clone had been established from a single murine brain cyst. The antibodies were
      bradyzoite-specific (4.3), tachyzoite-specific (4.25, 5.1 and anti-P(30)), or
      tachyzoite- and bradyzoite-specific (5.15). Their strong reactivity with the
      bradyzoite-specific mAb 4.3 and their weaker reactivity with the tachyzoite
      specific 4.25, 5.1 and anti-P(30) indicated that all the isolates are probably of
      genetic type II. Each of the isolates reacted in the IFAT in a similar way to the
      Danish reference strain of T. gondii, SSI-119.

PMID- 15949186
TI  - Rapid assessment of the geographical distribution of Mansonella perstans
      infections in Uganda, by screening schoolchildren for microfilariae.
AB  - The geographical distribution of Mansonella perstans infections in Uganda was
      assessed by day-time examination of school-aged children for microfilariae.
      Overall, 12,207 children from 76 sites representing the various topographical and
      ecological zones in the country were examined. Children with M. perstans
      microfilaraemia were detected at 47 (61.8%) of the study sites, with prevalences
      ranging from 0.4% to 72.8%. A broad, east-west-oriented belt of high endemicity
      was identified, stretching across the central part of the country from the
      southern end of Lake Albert to the north-western shores of Lake Victoria. To the
      north and south of this belt prevalences generally decreased, although high
      prevalence foci were also identified in the far north-western and south-eastern
      corners of the country. Geostatistical interpolation was used to create a map
      showing the geographical distribution of M. perstans prevalences in Uganda (by
      ordinary kriging), and to assess the population exposed to M. perstans
      transmission. Estimates based on population data from 2002 indicated that 20.4
      million people (82.6% of the national population) and 6.8 million people (27.5%
      of the national population) lived in areas where, respectively, >1% and >10% of
      the school-aged children had M. perstans microfilaraemias. Since the prevalence
      of M. perstans microfilaraemia is known to increase with age, the overall
      population prevalences are likely to be even higher than the prevalences observed
      in the school-aged children. More attention needs to be paid to the public-health
      implications of this wide-spread but neglected infection.

PMID- 15949187
TI  - Adverse reactions to the ivermectin treatment of onchocerciasis patients: does
      infection with the human immunodeficiency virus play a role?
AB  - To assess and compare the adverse effects resulting from ivermectin treatment of
      onchocerciasis patients with and without infection with human immunodeficiency
      virus (HIV-1), 1256 Ugandan cases of onchocerciasis were investigated as they
      were treated for the first time with the drug. Treatment followed the protocol of
      the Mectizan Expert Committee (i.e. a single dose of 150 mug/kg body weight).
      Adverse reactions to the ivermectin were determined, within 48 h of treatment,
      through questioning and clinical examinations during house-to-house visits. The
      HIV-1 status of each patient aged >15 years was initially determined using
      indirect ELISA, and any ELISA-positives were then confirmed in a western-blot
      assay. Among the cases aged >15 years, the frequency of adverse reactions to
      ivermectin was higher among those seropositive for HIV-1 (53.4%) than among the
      seronegative (45.7%) but the difference was not statistically significant (P =
      0.25). The severity of the adverse reactions observed was, however, significantly
      lower in the HIV-1-positive patients than in the seronegative patients, with
      median scores of 1.37 and 1.68, respectively (P = 0.044). The conclusion is that
      ivermectin can be safely used for mass treatment in areas where the prevalences
      of onchocerciasis and HIV-1 infection are both high.

PMID- 15949188
TI  - Electrocardiographic changes and myocarditis in trichinellosis: a retrospective
      study of 154 patients.
AB  - The frequencies of electrocardiographic (ECG) abnormalities and myocarditis were
      determined, retrospectively, among 154 cases of trichinellosis [101 males and 53
      females, with a mean (S.D.) age of 35.60 (14.64) years] who were hospitalized at
      the University Hospital for Infectious Diseases in Zagreb, Croatia, over a 5-year
      period. Eighty-seven (56%) of the patients, most of them in the invasive phase of
      infection with Trichinella spiralis, were found to have abnormalities when
      examined by 12-lead, resting electrocardiography. The ECG disorder most
      frequently observed was a non-specific ventricular repolarization disturbance
      (with ST-T wave changes), followed by bundle-branch conduction disturbances, and
      sinus tachycardia. The other ECG disorders recorded, during various phases of the
      infection, were sinus bradycardia, right bundle-branch block, supraventricular
      and ventricular extrasystoles, low-voltage QRS complexes in standard limb leads,
      first-degree atrio-ventricular block, and atrial fibrillation. Eighteen (12%) of
      the patients were identified as cases of myocarditis (13 in the invasive phase
      and five in the convalescent) and two (1.3%) as cases of myopericarditis. One
      patient developed acute myocardial infarction 28 days after the onset of disease
      and died soon thereafter; an autopsy revealed multiple necroses and fibroses of
      the myocardium and thrombus of a coronary artery. Although ECG abnormalities
      appear to be a common feature of trichinellosis, especially during the invasive
      phase of the disease, they are rarely associated with a poor prognosis. A
      transient, non-specific, ventricular-repolarization disturbance is the
      abnormality most commonly observed.

PMID- 15949189
TI  - Prevalence of the genes encoding extended-spectrum beta-lactamases, in
      Escherichia coli resistant to beta-lactam and non-beta-lactam antibiotics.
AB  - The prevalences of extended-spectrum beta-lactamases (ESBL) and their encoding
      bla genes, TEM, SHV and CTX_M, were investigated in isolates of Escherichia coli
      that were resistant to beta-lactam and/or non-beta-lactam antibiotics. Of the 250
      E. coli isolates investigated, all of which came from patients in a major
      hospital in southern Lebanon, 61 (13.3%) were found to have ESBL, their
      production of beta-lactamase being confirmed by the ceftazidime and
      ceftazidime/clavulanic-acid disc methods. All 61 ESBL isolates were resistant to
      beta-lactams and sensitive to imipenem, piperacillin/tazobactam and cefoxitime.
      Only 40% were resistant to fluoroquinolones, 33% were resistant to
      aminoglycosides, and 18% were considered to have multi-drug resistance. The
      results of the PCR-based amplification of the bla gene in DNA samples from the 61
      ESBL isolates indicated that 11 (18%) of the isolates carried both the TEM and
      SHV genes, 37 (61%) carried the TEM gene but not the SHV, and 13 (21%) had the
      SHV gene but not the TEM. None of the isolates carried the CTX_M gene. Of the 37
      TEM-positive/SHV-negative isolates, 43% were resistant to fluoroquinolones and
      37% to aminoglycosides. Increased resistance to non-beta-lactam antibiotics was
      observed in the isolates harbouring both the TEM and SHV genes, of which 54% were
      resistant to all of the tested antibiotics except imipenem, 36% were only
      resistant to fluoroquinolones, and 9.1% only resistant to aminoglycosides. The
      possibility that the concomitant presence of TEM- and SHV-type beta-lactamases is
      associated with resistance to non-beta-lactam antibiotics requires further
      research. The prevalences of ESBL and their encoding genes in Gram-negative
      bacteria collected from various regions in Lebanon will now be investigated.

PMID- 15949190
TI  - Molluscicidal activity of some Brazilian Solanum spp. (Solanaceae) against
      Biomphalaria glabrata.
AB  - Plants in the genus Solanum (Solanaceae) produce a great variety of steroidal
      saponins and glycoalkaloids that confer natural resistance against several pests.
      Methanolic extracts of 13 Solanum species have now been tested for molluscicidal
      activity against Biomphalaria glabrata. The extracts investigated were prepared
      from the fruit of S. asperum, S. capsicoides, S. palinacantum, S. paludosum, S.
      paniculatum, S. paraibanum and S. sisymbriifolium, the aerial parts of S.
      asperum, S. capsicoides, S. crinitum, S. diamantinense, S. megalonyx, S.
      palinacantum, S. paniculatum, S. sisymbriifolium and S. torvum, and the roots of
      S. asperum, S. asterophorum, S. palinacantum, S. paludosum, S. paniculatum and S.
      stipulaceum. Encouragingly, the extracts from S. asperum, S. diamantinese, S.
      paludosum, S. sisymbriifolium and S. stipulaceum showed significant molluscicidal
      activity, the median lethal concentrations recorded (20-50 microg/ml) falling
      well below the threshold, of 100 microg/ml, set for a potential molluscicide by
      the World Health Organization.

PMID- 15949191
TI  - Quinine for the treatment of chloroquine-resistant Plasmodium falciparum malaria
      in pregnant and non-pregnant Sudanese women.

PMID- 15949192
TI  - Age-related differences in the detection of Plasmodium falciparum infection by
      PCR and microscopy, in an area of Kenya with holo-endemic malaria.

PMID- 15949193
TI  - Subcutaneous dirofilariasis in southern India: a case report.

PMID- 15949194
TI  - Beyond 'tomorrow's doctors': a review of basic medical education in the UK.
AB  - Basic medical education in the UK has been radically reshaped in the past 15
      years, prompted by the General Medical Council who drove, supported and monitored
      the changes. Central aims of the reform included a reduction in curricular
      factual content, greater prominence of skills acquisition, eradication of the pre
      clinical/clinical divide and a higher profile for community-based teaching and
      learning. Some of the major developments are outlined, although change continues
      in other areas. Consequences of the initiative include greater choice in the
      courses now offered to applicants to medical school, the growth of medical
      education units within medical schools and greater interest in medical education
      generally.

PMID- 15949195
TI  - Diversity of disease in childhood pulmonary tuberculosis.
AB  - Many factors can influence the dynamic balance that exists between the host and
      the pathogen (M. tuberculosis), but the host immune response seems to be the most
      important. This is illustrated by the vulnerability of immune-compromised
      individuals to develop tuberculosis and by the age-related spectrum of disease
      witnessed in immune-competent children. This age-related spectrum of disease
      reflects the ontogeny of the host immune response towards M. tuberculosis.
      Renewing our focus on the ontogeny of the immune response in children might
      provide valuable insights to direct future research regarding tuberculosis
      prevention, vaccine development and treatment.

PMID- 15949196
TI  - Factors associated with severe anaemia in Zambian children admitted with
      Plasmodium falciparum malarial anaemia.
AB  - Many cases of severe malarial anaemia are clinically stable, but some can
      deteriorate rapidly. In a cross-sectional survey of 255 children with clinically
      stable malarial anaemia, 72 had severe anaemia (PCV < or = 15%) and 183 were
      moderately anaemic (PCV < 15-21%). Being female, or febrile, or a referral and
      having low parasitaemia or hepatomegaly were the risk factors for severe anaemia.

PMID- 15949197
TI  - Community effectiveness of malaria treatment in Uganda--a long way to Abuja
      targets.
AB  - INTRODUCTION: At the Roll Back Malaria summit for African countries in Abuja, the
      heads of state committed to ensure that by the year 2005 at least 60% of those
      suffering from malaria would have access to effective treatment within 24 hours
      of onset of symptoms. AIM: The aim of the study was to assess community
      effectiveness of malaria treatment in children. METHOD: A community-based survey
      of 500 households was undertaken in western Uganda. RESULTS: A total of 260 (52%)
      children were reported to have had fever within the previous 2 weeks: 87%
      received some kind of treatment, 44% were said to have been treated within 24
      hours of onset of symptoms, 47% received appropriate anti-malarials, 25% received
      the correct dosage, and 24% took the drug for the recommended period of time;
      altogether, only 7% received all the treatment steps. CONCLUSION: With drug
      efficacies of 50-90%, we estimate a community effectiveness of 4-6%, which is far
      from the 2005 Abuja target. The greatest need for improvement in the Home Based
      Fever Management strategy is in reducing delay in treatment and improving dosage
      and duration of treatment.

PMID- 15949198
TI  - Aetiology of neonatal sepsis in Blantyre, Malawi: 1996-2001.
AB  - AIM: The aim of this retrospective study was to report causes, antibiotic
      resistance and outcome of neonatal sepsis (often fatal in developing countries)
      in Malawi. METHODS: All blood and cerebrospinal fluid isolates collected between
      January 1996 and December 2001 from inpatients aged 0-30 days with suspected
      sepsis at Queen Elizabeth Central Hospital, Blantyre, Malawi were reviewed. In
      vitro resistance to antibiotics commonly used in Malawi was assessed. Case
      fatality rate was analysed with respect to age, bacterial pathogen and infection
      site. RESULTS: A total of 801 bacteria were isolated from 784 neonates over 6
      years-599 isolates from blood and 202 from cerebrospinal fluid. Overall, 54% of
      bacteria were gram-positive and 46% gram-negative. The commonest causes of
      neonatal sepsis were group B Streptococcus (17%) and non-typhoidal Salmonella
      (14%). In vitro antibiotic susceptibility to the first-line antibiotic
      combination of penicillin and gentamicin was 78% for all isolates, but in vitro
      sensitivities to gentamicin for Klebsiella spp and non-typhoidal Salmonella were
      only 33% and 53%, respectively. In-hospital case fatality rate was known for only
      301 cases and was high at 48%. Group B Streptococcus was associated with the best
      outcome. Mortality was significantly higher if presentation was in the 1st week
      of life or if sepsis was caused by gram-negative bacteria. The causes of neonatal
      sepsis in this population show a different pattern from other studies in
      developing countries.

PMID- 15949199
TI  - Cling wrap, an innovative intervention for temperature maintenance and reduction
      of insensible water loss in very low-birthweight babies nursed under radiant
      warmers: a randomized, controlled trial.
AB  - AIM: The value of polythene film ('cling wrap') to improve thermal control and
      reduce postnatal weight loss in preterm, very low-birthweight babies was
      investigated. METHODS: Consecutively born babies with birthweights between 750
      and 1500 g were stratified by birthweight (<1250 g, 1251-1500 g) and randomised
      either to the cling wrap (CW) or no cling wrap (NCW) group. The baby bassinette
      of the RW was covered with cling wrap up to the level of the neck in the CW group
      for the 1st 7 days. The primary outcome variables were the incidence of
      hypothermia (axillary temperature < or = 36 degrees C) after initial
      stabilisation during the first 7 days and cumulative weight loss (percentage of
      birthweight) at 48 hours of age. RESULTS: Of 51 babies, 26 were randomised to the
      CW and 25 to the NCW group. None of the babies in the CW group developed
      hypothermia in the 1st 7 days but 36% in the NCW group (p = 0.001) did. Babies
      who were hypothermic on admission took less time to reach normal temperature in
      the CW group. Cumulative weight loss in the 1st 48 hours was 5.0 + 5.6% in the CW
      group and 8.6 + 7.0% in the NCW group (p = 0.06). CONCLUSION: Use of CW might be
      a simple method of maintaining temperature in very low-birthweight babies in
      developing countries.

PMID- 15949200
TI  - Clinical features and treatment approaches in cystic fibrosis with pseudo-Bartter
      syndrome.
AB  - INTRODUCTION: Infants with cystic fibrosis (CF) are prone to develop episodes of
      hyponatraemic, hypochloraemic dehydration with metabolic alkalosis, which are
      biochemical hallmarks of the pseudo-Bartter syndrome (PB). METHOD: We reviewed
      the clinical and laboratory features and treatment approaches of 29 children with
      CF and PB who were under follow-up in our institution from May 1992 to November
      2003. RESULTS: Of 241 patients with CF, PB was detected in 29 (12%) with a median
      age of 4 months at the time of the first attack. Most patients experienced
      vomiting, loss of appetite and dehydration during episodes of PB. All patients
      were managed with intravenous fluids and sodium chloride solutions. During follow
      up, 12/29 cases required hospital admission for recurrent PB attacks. The oldest
      age at the time of the last attack was 48 months. CONCLUSIONS: CF should be
      considered in the differential diagnosis of metabolic alkalosis in young
      children. Vomiting and loss of appetite are important warning signs of possible
      PB in CF patients, particularly before 4 years of age. To prevent serious
      complications, it is crucial that parents and physicians recognise PB as early as
      possible.

PMID- 15949201
TI  - Carboxyatractyloside poisoning in humans.
AB  - OBJECTIVE: Cocklebur (Xanthium strumarium) is an herbaceous annual plant with
      worldwide distribution. The seeds contain the glycoside carboxyatractyloside,
      which is highly toxic to animals. We describe nine cases of carboxyatractyloside
      poisoning in humans which, to our knowledge, has not previously been reported.
      The clinical, laboratory and histopathological findings and our therapeutic
      approach are also discussed. SUBJECTS AND METHODS: The patients presented with
      acute onset abdominal pain, nausea and vomiting, drowsiness, palpitations,
      sweating and dyspnoea. Three of them developed convulsions followed by loss of
      consciousness and death. RESULTS: Laboratory findings showed raised liver
      enzymes, indicating severe hepatocellular damage. BUN and creatinine levels were
      raised, especially in the fatal cases who also displayed findings of consumption
      coagulopathy. CPK-MB values indicative of myocardial injury were also raised,
      especially in the fatal cases. Three of the patients died within 48 hours of
      ingesting carboxyatractyloside. Post-mortem histopathology of the liver confirmed
      centrilobular hepatic necrosis and renal proximal tubular necrosis, secondary
      changes owing to increased permeability and microvascular haemorrhage in the
      cerebrum and cerebellum, and leucocytic infiltrates in the muscles and various
      organs including pancreas, lungs and myocardium. CONCLUSIONS:
      Carboxyatractyloside poisoning causes multiple organ dysfunction and can be
      fatal. Coagulation abnormalities, hyponatraemia, marked hypoglycaemia, icterus
      and hepatic and renal failure are signs of a poor prognosis. No antidote is
      available and supportive therapy is the mainstay of treatment.

PMID- 15949202
TI  - Long-term results of topical glyceryl trinitrate ointment in children with anal
      fissure.
AB  - BACKGROUND/AIM: Although topical glyceryl trinitrate ointment (GTN) has become a
      popular treatment for anal fissure in adults, its use in children is still
      limited. We aimed to determine the effectiveness and safety of topical GTN in the
      long-term management of anal fissure in children, which has not yet been
      reported. METHODS: Thirty-one children with anal fissure who received topical
      0.2% GTN treatment between 1997 and 1998 were evaluated in 2004. RESULTS: Ten
      patients had one or more relapses after initial treatment with 0.2% GTN, all
      within 1 year of first onset of anal fissure. No further recurrences were
      diagnosed during the 4-year follow-up period. CONCLUSION: Although early
      recurrence can occur, topical GTN ointment is effective in healing chronic anal
      fissures in children.

PMID- 15949203
TI  - Cytomegalovirus infection in neonates following blood component therapy.

PMID- 15949204
TI  - Acute acalculous cholecystitis in a child with Plasmodium falciparum malaria.
AB  - We report a 7-year-old girl who presented with features of acute acalculous
      cholecystitis. She was found to be positive for Plasmodium falciparum. To the
      best of our knowledge, this is the first report of acalculous cholecystitis
      caused by P. falciparum in a child.

PMID- 15949205
TI  - Osteomyelitis of the ischium: unusual presentation.
AB  - A 7-year-old boy presented with urinary symptoms and umbilical discharge. A
      perivesical abscess was drained from which Staphylococcus aureus was cultured. He
      responded to antibiotics. Subsequently, he developed a discharging sinus in the
      gluteal region. A plain radiograph, which had previously been normal, confirmed
      osteomyelitis of the ischial bone.

PMID- 15949206
TI  - Hypernatraemic dehydration in breastfed infants: is caesarean section a risk?

PMID- 15949208
TI  - How would revealing the identity of gamete donors affect current practice?
AB  - The possibility of revealing the identity of gamete donors may change the
      decision of a donor to collaborate with infertility clinics and patients.
      Previous experiences with patients and donors, as well as different cultural
      viewpoints in northern and southern Europe, are presented.

PMID- 15949209
TI  - Optimizing GnRH antagonist administration: meta-analysis of fixed versus flexible
      protocol.
AB  - A meta-analysis was conducted to investigate whether flexible gonadotrophin
      releasing hormone (GnRH) antagonist administration according to follicular size
      would be more beneficial than starting on a fixed day. Only randomized controlled
      trials were included after a comprehensive search strategy. The data were
      combined for meta-analysis with RevMan software. Eleven trials were identified,
      but only four randomized controlled trials met the inclusion criteria. There was
      no statistically significant difference in pregnancy rate per woman randomized,
      although there was a trend towards a higher pregnancy rate with the fixed
      protocol, especially with delayed administration beyond day 8 [odds ratio (OR)
      0.7, 95% confidence interval (CI) 0.45-1.1]. There was no premature LH surge in
      any participant in either protocol. However, there was a statistically
      significant reduction both in number of antagonist ampoules (OR -1.2 95%, CI 
      1.26 to -1.15) and amount of gonadotrophin (OR 95.5 IU, 95% CI 74.8-116.1) used
      in the flexible protocol. In conclusion, there was no statistically significant
      difference in pregnancy rate between flexible and fixed protocols. There was a
      statistically significant reduction in the amount of recombinant FSH with the
      flexible protocol.

PMID- 15949210
TI  - Is the occurrence of the empty follicle syndrome a predictor that a subsequent
      stimulated cycle will be an unfavourable one?
AB  - Several hypotheses have been advanced to explain empty follicle syndrome (EFS)
      but it remains a controversial topic. This paper reports experience with three
      IVF cycles in which no oocytes were collected. In all cases, an additional IVF
      cycle was performed. The ovarian stimulation protocol, ultrasound and hormonal
      surveillance methods, human chorionic gonadotrophin timing and oocyte retrieval
      technique were similar in all patients. The assessment of additional cycles
      demonstrated a poor response in terms of oocyte quality, since the number of
      mature oocytes was low despite the high number of oocytes collected. Thus, the
      data suggest that in these patients, EFS should be considered as a borderline
      form of poor response to ovarian stimulation. If this is confirmed, EFS should be
      a recurrent event and an empty cycle could be a good predictor that a subsequent
      stimulated cycle will be an unfavourable.

PMID- 15949212
TI  - Recombinant gonadotrophin-based, ovarian hyperstimulation syndrome-free
      stimulation of the high responder: suggested protocol for further research.
AB  - Ovarian stimulation of the high responder remains controversial. The narrow
      margin between a too low gonadotrophin dose (and abnormal oestradiol rise) and
      excessive stimulation (risk of OHSS) is a challenging situation. This study
      describes an OHSS-free protocol, based on the use of recombinant gonadotrophins
      for stimulation and gonadotrophin-releasing hormone (GnRH) antagonist to prevent
      premature LH surge. In six patients with a previous history of excessive
      response, stimulation was started on day 3 of cycle with recombinant FSH. When
      follicular diameter reached 13-14 mm, a daily injection of GnRH antagonist was
      added, together with a daily dose of 75 IU of recombinant LH. When the leading
      follicles reached 17 mm in diameter, ovulation was triggered with a single dose
      of 0.2 mg triptorelin. Luteal support with vaginal oestradiol and progesterone
      was started on the day of oocyte retrieval. None of the patients developed
      clinically significant OHSS. Mean maximal oestradiol concentration was 23,209
      pmol/l, and mean number of embryos obtained per patient was 20.5. Fresh embryo
      transfer resulted in one ongoing pregnancy and two chemical pregnancies. Thaw
      cycles have resulted so far in two additional ongoing pregnancies. This protocol
      removes the risk of OHSS and has a good clinical outcome, and therefore merits
      further research.

PMID- 15949213
TI  - A rational approach to oocyte cryopreservation.
AB  - Reports of clinical pregnancies from cryopreserved human oocytes have been
      steadily increasing in recent years. However, success in terms of births per
      thawed oocyte remains poor. A wide variety of freezing techniques has been used
      lately, but modifications to protocols are made on an empirical basis. Methods of
      cryopreservation are often poorly described or protocols are not strictly adhered
      to, resulting in variability of outcome. The first stage of a freezing protocol
      is exposure to cryoprotectant. If performed inappropriately, such exposure can
      result in damage due to chemical toxicity and/or osmotic stress. Measurement of
      cell volume change during exposure to cryoprotectants demonstrates the extent of
      osmotic stress experienced by that cell. Such measurements have been performed
      during perfusion of murine and human oocytes with cryoprotectant concentrations
      commonly used for cryopreservation of these cells. It has been demonstrated that
      changes in the cryoprotectant type, concentration and temperature of exposure can
      dramatically affect the extent of cell volume change. Even small changes in
      duration of exposure to cryoprotectant prior to cooling can result in drastic
      changes in cellular hydration. Such factors will potentially influence the
      ability of the cell to survive the stresses experienced during the subsequent
      stages of the cryopreservation protocol.

PMID- 15949215
TI  - Immature oocyte in-vitro maturation: clinical aspects.
AB  - The development of immature oocyte collection techniques for in-vitro maturation
      (IVM), combined with novel culture techniques, opens new possibilities for
      assisted reproductive technology. Optimization of clinical management of IVM
      cycles will enhance pregnancy outcome, so that IVM might become an effective
      alternative assisted reproduction treatment for infertile patients irrespective
      of the cause of infertility. Parameters such as age and baseline antral
      follicular count are predictive of outcome and should be used as selection
      criteria for IVM treatment. Women with polycystic ovary disease and normo
      ovulatory patients at risk of developing ovarian hyperstimulation syndrome might
      benefit from earlier retrieval of oocytes followed by IVM and embryo transfer.
      HCG priming before oocyte retrieval seems beneficial in terms of oocyte yield and
      maturational competence, and may increase the harvest of mature oocytes and lead
      to better endometrial synchronization with the developing embryo. The timing of
      aspiration may be crucial in IVM and selection criteria for follicle size at
      aspiration need defining prospectively for infertility type. Finer calibre
      aspiration needles and low aspiration pressure yield more oocytes. A combination
      of natural cycle IVF with IVM is a promising, mild and inexpensive assisted
      reproduction treatment, widely accessible the infertile population.

PMID- 15949216
TI  - Strategies in human in-vitro maturation and their clinical outcome.
AB  - The basis of in-vitro maturation (IVM) is the maturing in vitro of oocytes from
      the germinal vesicle (GV) stage of development to the metaphase II stage.
      Experience in handling immature oocytes has been obtained from two main groups.
      The first group is women suffering from polycystic ovarian syndrome, who are
      extremely sensitive to stimulation with exogenous gonadotrophins in assisted
      reproduction, and have a significant risk of developing ovarian hyperstimulation
      syndrome (OHSS). The second group is regular cycling women with normal ovaries
      referred for IVF due to severe male infertility. In both groups, aspiration of
      immature oocytes has been performed in unstimulated cycles and after priming with
      human chorionic gonadotrophin or FSH respectively. Clinical pregnancy rates of
      24% per aspiration have been obtained. Children born after IVM appear to be
      healthy. These data, taken together, suggest that in future, immature oocyte
      retrieval combined with IVM could replace conventional IVF in selected patients.

PMID- 15949217
TI  - Comparison of four media types during 3-day human IVF embryo culture.
AB  - The aim of this study was to compare the effectiveness of human tubal fluid
      (HTF), G1.2, Sage Cleavage and Life Global media for IVF outcome during 3-day
      culture of human embryos. A three-phase auto-controlled study was conducted in
      which IVF outcome was compared between (1) HTF and G1.2, (2) HTF and Cleavage,
      and (3) Cleavage and Life Global. In phase 1, no differences in embryo quality
      were observed between HTF and G1.2. However, embryos derived from
      intracytoplasmic sperm injection (ICSI) displayed significantly improved quality
      when grown in HTF versus G1.2. No differences in pregnancy and implantation rates
      were observed in cases where embryos transferred were grown exclusively in HTF or
      G1.2 media. In phase 2, embryo quality was significantly improved for embryos
      cultured in Cleavage versus HTF media (P < 0.001). However, pregnancy,
      implantation and spontaneous abortion rates were similar between the two media.
      In phase 3, there were no differences in embryo quality, pregnancy, implantation,
      and spontaneous abortion rates between Cleavage and Life Global media. Overall,
      the data indicate that Life Global and Cleavage media yield similar results in a
      3-day IVF culture programme. Cleavage medium is superior to HTF, as evidenced by
      significantly improved embryo quality (P < 0.001). Meanwhile, HTF medium is
      superior to G1.2 for ICSI cases.

PMID- 15949218
TI  - Gene expression in the preimplantation embryo: in-vitro developmental changes.
AB  - The regulation of early embryo development and the mechanism of implantation
      remains poorly understood, due to the large number of genes and the complexity of
      the systems involved. The effect of in-vitro culture on embryos also remains
      unclear, which raises concerns about the safety of assisted reproductive
      technology. Changes in the expression of several individual genes in cultured
      embryos have been reported previously, but a large-scale comparison has not yet
      been performed to investigate the effects of in-vitro culture systems on embryo
      development. This study investigated established gene expression profiles of more
      that 20,000 genes from in-vitro cultured mouse embryos at eight different stages
      (oocytes, zygote, 2-, 4-, 8-cell embryo, compacting embryo, morula and
      blastocyst) using microarray technology, and compared these profiles with in-vivo
      embryos. In most stages of development there was little significant difference in
      overall expression patterns between in-vitro and in-vivo embryos. In addition,
      the expression patterns of developmentally important genes from several different
      categories, such as apoptosis, glycolysis, adhesion and methylation, were
      examined and compared between in-vitro and in-vivo embryos. Among the genes
      examined, DNA methyltransferase 1 (DNMT1) shows a significantly higher (P < 0.05)
      expression level in cultured embryos. Cadherin-11 also demonstrates a slightly
      different pattern, although the difference is not statistically significant. All
      the other genes have remarkably similar expression patterns between in-vitro and
      in-vivo embryos throughout preimplantation stages.

PMID- 15949219
TI  - Establishment and characterization of new human embryonic stem cell lines.
AB  - Human embryonic stem cells (hESC), with their ability to differentiate into all
      cell types in the human body, are likely to play a very important therapeutic
      role in a variety of neurodegenerative and life-threatening disorders in the near
      future. Although more than 120 different human embryonic stem cell lines have
      been reported worldwide, only a handful are currently available for researchers,
      which limits the number of studies that can be performed. This study reports the
      isolation, establishment and characterization of new human embryonic stem cell
      lines, as well as their differentiation potential into variety of somatic cell
      types. Blastocyst-stage embryos donated for research after assisted reproductive
      techniques were used for embryonic stem cell isolation. A total of 31 blastocysts
      were processed either for immunosurgery or direct culture methods for inner cell
      mass isolation. A total of nine primary stem cell colonies were isolated and of
      these, seven cell lines were further expanded and passaged. Established lines
      were characterized by their cellular and colony morphology, karyotypes and
      immunocytochemical properties. They were also successfully cryopreserved/thawed
      and showed similar growth and cellular properties upon thawing. When induced to
      differentiate in vitro, these cells formed a variety of somatic cell lineages
      including cells of endoderm, ectoderm and mesoderm origin. There is now an
      exponentially growing interest in stem cell biology as well as its therapeutic
      applications for life-threatening human diseases. However, limited availability
      of stem cell lines as well as financial or ethical limitations restrict the
      number of research projects. The establishment of new hESC lines may create
      additional potential sources for further worldwide and nationwide research on
      stem cells.

PMID- 15949221
TI  - Influence of maternal age on the outcome of PGD for aneuploidy screening in
      patients with recurrent implantation failure.
AB  - This study assessed the influence of maternal age on the outcome of aneuploidy
      screening (AS) cycles for recurrent implantation failure (RIF). One hundred and
      sixteen couples with a history of RIF underwent 130 cycles of AS. Group A
      included 78 patients aged < or = 40 years (range 25-40 years) who underwent 86
      cycles, while group B included 38 couples aged > or = 41 (range 41-47) who
      underwent 44 cycles. Fluorescence in-situ hybridization (FISH) analysis of the
      first and second polar bodies using probes specific for chromosomes 13, 16, 18,
      21 and 22 was conducted. Euploid oocytes that cleaved were subsequently tested
      using the same probes on a single blastomere obtained from day 3 embryos.
      Chromosomally normal embryos were replaced on day 5 of culture. There was no
      significant difference between the two groups in the mean numbers of oocytes
      fertilized normally and oocytes (7.5 +/- 3.2 versus 7.2 +/- 3.6) and embryos
      tested (4.1 +/- 3 versus 3.4 +/-3). However, the younger age group had a
      significantly higher proportion of euploid oocytes/embryos, cycles reaching
      embryo transfer, pregnancy (43 versus 25%), clinical pregnancy (36.1 versus
      16.6%) and ongoing delivery (32 versus 12.5%) rates per transfer. Preimplantation
      genetic diagnosis with AS for recurrent IVF implantation failure using FISH
      probes is therefore associated with improved outcome in women under 41 years, but
      has a high cancellation rate and low cycle outcome in older women.

PMID- 15949222
TI  - The beneficial effects of preimplantation genetic diagnosis for aneuploidy
      support extensive clinical application.
AB  - The aim of this study was to evaluate the clinical impact of preimplantation
      genetic diagnosis (PGD) for aneuploidy on 193 patients who subsequently achieved
      208 clinical pregnancies, in relation to their reproductive history. The 208
      clinical pregnancies included in the study resulted from 1029 assisted conception
      cycles in combination with PGD for aneuploidy in 740 couples with a history of
      poor reproductive performance. According to the reproductive history of the 193
      patients, 61 had previously experienced 112 pregnancies with 105 abortions and
      seven deliveries, corresponding to 3.6% take-home baby rate and 10.9%
      implantation rate. During the PGD cycle, preimplantation embryos were analysed
      for 5-9 chromosomes. The transfer of euploid embryos was performed in 699 cycles
      (68% of oocyte retrievals), generating 171 term pregnancies with 210 infants
      born, whereas 34 aborted spontaneously and three were ectopic, giving a take-home
      baby rate per pregnant patient of 88.6% and an ongoing implantation rate per
      pregnant patient of 53.2%. According to these data, selection made in
      preimplantation embryos against chromosomal abnormalities is associated with a
      significantly higher (P < 0.001) take-home baby rate when compared with the
      previous reproductive history of the parents.

PMID- 15949223
TI  - Birth of two healthy females after preimplantation genetic diagnosis for familial
      amyloid polyneuropathy.
AB  - Familial amyloid polyneuropathy (FAP), Portuguese type, is a late onset, high
      penetrance, autosomal dominant Mendelian disorder caused by a V30M substitution
      in the transthyretin (TTR) protein. A genetic diagnosis was developed using
      fluorescent single cell polymerase chain reaction (PCR) on lymphocytes from
      patients and controls. Ovarian stimulation and oocyte retrieval were carried out
      using conventional protocols in a couple in whom the female was heterozygous for
      the mutation TTR V30M. Blastomere biopsy was performed on day 3 after
      intracytoplasmic sperm injection. PCR was then performed for a segment of the TTR
      gene encompassing the V30M mutation. The transfer of three embryos at day 4
      resulted in a twin pregnancy, confirmed as healthy females by amniocentesis at 16
      weeks of gestation; the birth took place at 37 weeks of gestation. With this
      report, FAP, TTR related, joins the lengthening list of genetic conditions for
      which preimplantation genetic diagnosis has been successfully carried out.

PMID- 15949224
TI  - Factors predicting IVF treatment outcome: a multivariate analysis of 5310 cycles.
AB  - The objective of this study was to analyse factors predicting live birth rate
      following IVF. A computerized database of 1928 women who underwent 5310
      consecutive IVF cycles in a single IVF unit was evaluated. Data on the women's
      age, number of retrieved oocytes, performance of intracytoplasmic sperm injection
      (ICSI), aetiology of infertility, number of transferred embryos and option of
      choosing embryos for transfer were evaluated. There were 1126 pregnancies that
      resulted in 689 live births. Transferring two embryos doubled the chances of
      delivery compared with one embryo, but transferring three embryos was not
      significantly superior to two embryos. Moreover, following a three-embryo
      transfer, the multiple delivery rates were significantly higher (P < 0.01)
      compared with transferring two embryos. Optimal delivery rates were observed in
      women aged 26-30 years, with gradual decline with advanced age. The performance
      of ICSI resulted in higher delivery rates compared with conventional
      insemination. According to these data, the best live birth results following IVF
      treatment were achieved when the maternal age was 26-30 years, in couples with
      male factor infertility undergoing ICSI, and when two embryos were transferred.

PMID- 15949225
TI  - Ongoing pregnancy after ICSI of frozen-thawed PESA-retrieved spermatozoa and IVF
      in a controlled natural cycle.
AB  - The recovery of a mature oocyte from a natural cycle followed by IVF (nIVF) is an
      attractive alternative to conventional IVF, involving ovarian stimulation, in the
      treatment of female infertility. Similarly, surgical recovery of spermatozoa from
      the epididymis by percutaneous sperm aspiration (PESA) has simplified the
      treatment of men with obstructive azoospermia. A couple sought treatment for
      diminished ovarian reserve and male factor infertility using IVF. A mature oocyte
      was retrieved and was inseminated by intracytoplasmic sperm injection (ICSI),
      following recovery of spermatozoa by PESA. A good quality embryo was transferred.
      A viable pregnancy was confirmed by ultrasound scan. A healthy baby boy was
      delivered naturally at 37 weeks gestation. This study reports the first ongoing
      clinical pregnancy and subsequent birth resulting from ICSI of spermatozoa
      retrieved by PESA into an oocyte recovered during a natural cycle. The use of a
      combination of less invasive assisted reproductive techniques (PESA and nIVF) can
      overcome barriers to fertility.

PMID- 15949227
TI  - Predictive factors for embryo implantation potential.
AB  - In spite of recent improvements in IVF, pregnancy rates have not increased
      significantly and one of the major problems remains the high multiple pregnancy
      rate. Better criteria are therefore necessary to establish the viability of a
      transferable embryo. Early prognosis of the developmental fate of the oocyte
      would help in selecting the best embryos to transfer, but non-invasive selection
      at the oocyte stage (extracytoplasmic and intracytoplasmic morphology) has proved
      to be of little prognostic value. Recently, it has been shown that follicular
      vascularization appears to be predictive of oocyte developmental fate, making it
      a good first-step approach for selection. Observation of pronuclei patterns at
      the zygote stage appears to offer an additional prognostic tool, correlating well
      with IVF outcome. Morphological evaluation of the embryo at days 2-3 remains the
      most used and valid method of selection, even though it is not sufficient to
      select embryos with the higher implantation potential. Blastocyst culture is
      another possible strategy for selecting the best embryos with reduced risk of
      aneuploidies, though not all major chromosomal aberrations are excluded by
      prolonged in-vitro culture. In summary, selecting the best embryo for transfer is
      a decision that should be based on choices made during the different stages of
      assisted reproductive technologies.

PMID- 15949228
TI  - Significance of morphological attributes of the early embryo.
AB  - There are many morphological transformations during development of human embryos
      that mainly involve phenomena that can be easily assessed in living embryos by
      simple non-invasive microscopical observation. A clear correlation between
      pronuclear morphology and the ability of the resulting embryo to continue
      developing and to implant has been described. There is also general agreement
      that a positive relationship exists between early embryo morphology and
      implantation rate. The parameters classically involved in embryo evaluation are:
      cleavage rate, blastomere symmetry, cytoplasmic appearance, extent of
      fragmentation and blastomere nuclear status. In this paper, morphological
      features that have been related to embryo developmental potential are described.
      Furthermore, the ability of a cumulative classification scheme developed in the
      laboratory to predict blastocyst formation and implantation is analysed.

PMID- 15949229
TI  - Oxytocin receptors in brain cortical regions are reduced in haploinsufficient (+/
      ) reeler mice.
AB  - OBJECTIVE: Both oxytocin (OT) and reelin are particularly significant during
      development and the absence of either may interfere with normal brain
      development. In addition, reelin is critical to the development of the GABAergic
      system and GABA modulates the release of OT. Availability of the reelin
      haploinsufficient (+/-) reeler mouse (HRM) provides a model for examining the
      role of reelin in the development of the OT system and especially in the
      expression of the OT receptor (OTR). METHODS: In this study we used
      immunocytochemistry and in situ hybridization in HRM versus wild-type (+/-) mice
      (WTM) to quantify OTR abundance in regions of the brain cortex. RESULTS: Our
      findings reveal that the oxytocin receptor (OTR), measured either by
      immunohistochemistry or in situ hybridization, is significantly lower in HRM.
      Areas showing significant deficits included the piriform cortex, neocortex,
      retrosplenial cortex and certain regions of the hippocampus. CONCLUSION: Both
      reelin and OT play a role in regulating affect and mood. Down-regulation of
      reelin has been strongly correlated with schizophrenia and it is proposed that
      HRM may serve as a model for neural deficits seen in both schizophrenia and
      autism. We report that HRM show regionally specific reductions in OTRs,
      especially in cortical areas, which previously have been implicated in social
      memory and cognitive functions. These findings offer support for the more general
      hypothesis that down-regulation of reelin, of either genetic or epigenetic
      origin, through associated reductions in the OTRs, contributes to the
      deficiencies in social behavior that are characteristic of both schizophrenia and
      autism.

PMID- 15949230
TI  - Radiation-induced apoptosis of oligodendrocytes in the adult rat optic chiasm.
AB  - OBJECTIVES: The present study characterized glial cell injury provoked in adult
      rat chiasm within 24 hours after a single, high-dose irradiation of 20 Gy.
      METHODS: All chiasmal glial cells in a section were counted, and the percentage
      of TUNEL-positive glial cells exhibiting apoptotic morphology was defined as the
      apoptotic rate. RESULTS: Numbers of apoptotic cells increased significantly
      (p<0.0001) from 3 to 8 hours after exposure, but returned to baseline levels by
      24 hours. Little evidence of apoptosis was observed in non-irradiated chiasms.
      Similar patterns of increase in apoptotic rate were observed in the genu of the
      corpus callosum, but the extent was significantly lower (p=0.047) in the optic
      chiasm, with a maximal rate of 1.9%. Immunohistochemically, apoptotic cells were
      positive for CNP, a marker for oligodendrocytes. DISCUSSION: These data indicate
      that chiasmal irradiation induces limited, but significant apoptotic depletion of
      the oligodendroglial population, and may participate in the development of
      radiation-induced optic neuropathy.

PMID- 15949231
TI  - Evaluation of intra-operative ultrasound imaging in brain tumor resection: a
      prospective study.
AB  - AIMS: The purpose of our study was to evaluate intra-operative ultrasound (IOUS)
      as a tool of resection control after brain tumor surgery. In addition, we looked
      for tumor species suitable for ultrasound representation. METHODS: Using a
      Siemens Omnia Sonoline Ultrasound, 36 tumors were examined, high-grade gliomas
      (62%), metastases (22%) and others (16%). We focused on tumor imaging by
      ultrasound with regard to its reliability of tumor expansion and margins.
      Evaluation of the images was carried out by correlating the ultrasound-based
      intra-operative measured tumor volume before and after resection with a pre- and
      post-operative (within 48 hours) measured volume by MRI. The IOUS measurements
      were performed by the neurosurgeon and the MRI measurements by the
      neuroradiologist. Thus, the measurement procedures were blinded. Corresponding to
      a deviation of the ultrasound volume by 10, 20 and > 20% from the MRI volume, the
      correlation was ranked good, moderate and poor. For assessing the agreement
      between these two methods of imaging, the statistical analysis was conducted
      using a method described by Bland and Altman. RESULTS: High-grade gliomas mostly
      showed a moderate or poor correlation in comparing IOUS- and MRI-tumor volumetry
      resulting in incomplete resection. Metastases resulted in a good to moderate
      correlation with a satisfactory extent of resection. The other tumors had poor
      images with larger tumor residues. The MRI measured volumes tended to be larger
      on average; the deviation grew with tumor size . CONCLUSION: The reliability of
      IOUS depends on tumor type. It is beneficial to use IOUS for the resection of
      metastases and a few high-grade gliomas. Concerning the volumetric accuracy, the
      value of IOUS is worse than its value of navigation and resection control.

PMID- 15949232
TI  - Accuracy of frameless and frame-based image-guided stereotactic brain biopsy in
      the diagnosis of glioma: comparison of biopsy and open resection specimen.
AB  - OBJECTIVES: Tissue heterogeneity and rapid tumor progression may decrease the
      accuracy a prognostic value of stereotactic brain biopsy in the diagnosis of
      gliomas. Correct tumor grading is therefore dependent on the accuracy of biopsy
      needle placement. There has been a dramatic increase in the utilization of
      frameless image-guided stereotactic brain biopsy; however, its accuracy in the
      diagnosis of glioma remains unstudied. METHODS: The diagnoses of 21 astrocytic
      brain tumors were derived using image-guided stereotactic biopsy (12 frame-based,
      nine frameless) and followed by open resection of the lesion 1.5 (0.5-4) months
      later. The histologic diagnoses yielded by the biopsy were compared with
      subsequent histologic diagnosis from open tumor resection. RESULTS: Histology of
      21 stereotactic biopsies accurately represented the greater lesion at open
      resection a median of 45 days later in 16 (76%) cases and correctly guided
      therapy in 19 (91%) cases. Biopsy accuracy of frameless versus frame-based
      stereotaxis was similar (89 versus 66%, p=0.21). In three (14%) cases, biopsy
      specimens were adequate to diagnose glioma; however, histology was insufficient
      for definitive tumor grading. Anaplastic oligodendroglioma (ODG) was under-graded
      as low-grade ODG in one (5%) case. Biopsy of new onset glioblastoma multiforme
      (GBM) yielded necrosis/gliosis and was termed non-diagnostic in one patient.
      Tumors <50 cm(3) were 8-fold less likely to accurately represent the grade of the
      entire lesion at resection compared with lesions <50 cm(3) (OR, 8.8; 95% CI, 0.9
      100, p=0.05). DISCUSSION: Both frameless and frame-based MRI-guided stereotactic
      brain biopsy are safe and accurately represent the larger glioma mass
      sufficiently to guide subsequent therapy. Large tumor volume had a higher
      incidence of non-concordance. Increasing the number of specimens taken through
      the long dimension of large tumors may improve diagnostic accuracy.

PMID- 15949233
TI  - An adaptive level set method for interactive segmentation of intracranial tumors.
AB  - BACKGROUND: Meaningful segmentation of intracranial lesions can be of assistance
      for planning open navigated microneurosurgical procedures, as well as for
      radiotherapy. Meaningful segmentation, however, may be hampered by lack of
      computational power. The respective segmentation method should be based on state
      of-the-art mathematical tools, and it should be suitable for real applications.
      METHODS: A three-dimensional computational method for interactive segmentation of
      intracranial tumors is presented. It is based on a front propagation method, in
      which the evolving front gradually approaches the boundary of a given segment. It
      generates and remembers the entire evolution of the interface. The segment
      boundary is chosen from a one parameter family. User interaction is realized by
      selecting "seed points" inside the object/lesion. External evolution velocity
      regulates the segmentation process, while approaching the boundary. Adaptively
      resolved grids ensure computational efficiency for larger segments. The
      resolution is steered by an image-based indicator, which allows coarse
      representation of the solution in low-frequency regions, but high resolution
      along suspected edges of the image. RESULTS: Model-based segmentation was
      performed on the imaging data of n = 12 patients and the results compared with
      manual segmentation of the same tumors. The method allowed for basic segmentation
      in all tumors <3 minutes. This increased 2-4 fold in four irregular tumors, where
      discrepancies existed in comparison with manually performed segmentation.
      DISCUSSION: The implicit formulations of this method establish methodical and
      topological flexibility in three dimensions. It is thus suitable for the
      segmentation of objects with non-sharp boundaries such as intracranial tumors.

PMID- 15949234
TI  - Expression of VEGF and its receptors in different brain tumors.
AB  - INTRODUCTION: Vascular endothelial growth factor (VEGF) and its receptors VEGFR-1
      and -2 are considered to play a major in tumor angiogenesis, which is a
      prerequisite for growth of solid tumors. Glioblastoma multiforme is a prominent
      example of VEGF-induced tumor vascularization; however, little is known about
      VEGF and in particular VEGFR expression in other types of brain tumors. METHODS:
      VEGFR mRNA was quantified by real time RT-PCR in 12 different types of brain
      tumors and compared to VEGF protein content measured by ELISA. VEGF splice
      variants were determined by an RT-PCR method. RESULTS: VEGF protein was highest
      in glioblastoma and metastatic kidney tumors. In all types of tumors the
      diffusible splice forms VEGF(121) and VEGF(165) were expressed; VEGF(189) was
      minor in a few tumors. Expression of VEGF receptors did not necessarily correlate
      with VEGF content. Both were highly expressed in glioblastomas, but in
      meningiomas VEGF was low and VEGFR high, and in metastatic tumors the reverse.
      With few exceptions, in particular oligodendrogliomas, VEGFR-1 expression was
      parallel to VEGFR-2 expression. Interestingly, for the astrocytic gliomas, the
      expression of VEGFR correlated well to the tumor malignancy, even better than
      VEGF content. CONCLUSIONS: These results show that VEGF and VEGFR expression in
      various types of brain tumors differ and are not necessarily parallel.

PMID- 15949235
TI  - Diffuse encephaloventriculitis and substantial leukoencephalopathy after
      intraventricular administration of recombinant adenovirus.
AB  - OBJECTIVES: The use of recombinant adenovirus as a vehicle for gene transfer into
      ependymal cells is a potential therapeutic tool for the treatment of various
      neural disorders. However, gene transfer into the ependymal cells of the
      ventricular wall is associated with high-level expression of the transferred
      gene, which declines rapidly. The purpose of this study is to understand the
      cause of this early decline in gene expression. METHODS: Different doses of
      adenovirus-expressing beta-galactosidase (Ad-beta-gal) were injected into the
      lateral brain ventricle of C57BL/6 mice, and the brains were observed
      histologically and with magnetic resonance (MR) imaging for a month. RESULTS:
      Inoculation of the lateral ventricle with more than 1 x 10(8) viral particles
      (2.6 x 10(6) pfu) resulted in a rapid decline of beta -gal expression. MR imaging
      indicated gradual ventriculomegaly and histological analysis showed the loss of
      the ependymal cells from the ventricular wall, lymphocytes infiltration near the
      wall, degeneration of myelinated fibers and apoptosis in the external capsule.
      Reactive astrocytes proliferated in the external capsule 17 days following
      inoculation. To avoid this irreversible brain atrophy, the inoculated adenovirus
      should be reduced to less than 1 x 10(7) particles (2.6 x 10(5) pfu) in mice.
      DISCUSSION: Our results indicate the presence of a unique and diffuse immune
      response of the brain; therefore, the clinical use of recombinant virus for
      intraventricular gene transfer must be carefully evaluated.

PMID- 15949236
TI  - Are gadolinium contrast agents suitable for gadolinium neutron capture therapy?
AB  - OBJECTIVE: Gadolinium neutron capture therapy (GdNCT) is a potential treatment
      for malignant tumors based on two steps: (1) injection of a tumor-specific
      (157)Gd compound; (2) tumor irradiation with thermal neutrons. The GdNC reaction
      can induce cell death provided that Gd is proximate to DNA. Here, we studied the
      nuclear uptake of Gd by glioblastoma (GBM) tumor cells after treatment with two
      Gd compounds commonly used for magnetic resonance imaging, to evaluate their
      potential as GdNCT agents. METHODS: Using synchrotron X-ray spectromicroscopy, we
      analyzed the Gd distribution at the subcellular level in: (1) human cultured GBM
      cells exposed to Gd-DTPA or Gd-DOTA for 0-72 hours; (2) intracerebrally implanted
      C6 glioma tumors in rats injected with one or two doses of Gd-DOTA, and (3) tumor
      samples from GBM patients injected with Gd-DTPA. RESULTS: In cell cultures, Gd
      DTPA and Gd-DOTA were found in 84% and 56% of the cell nuclei, respectively. In
      rat tumors, Gd penetrated the nuclei of 47% and 85% of the tumor cells, after
      single and double injection of Gd-DOTA, respectively. In contrast, in human GBM
      tumors 6.1% of the cell nuclei contained Gd-DTPA. DISCUSSION: Efficacy of Gd-DTPA
      and Gd-DOTA as GdNCT agents is predicted to be low, due to the insufficient
      number of tumor cell nuclei incorporating Gd. Although multiple administration
      schedules in vivo might induce Gd penetration into more tumor cell nuclei, a
      search for new Gd compounds with higher nuclear affinity is warranted before
      planning GdNCT in animal models or clinical trials.

PMID- 15949237
TI  - Pituitary apoplexy as a consequence of lymphocytic adenohypophysitis in a
      pregnant woman: a case report.
AB  - OBJECTIVE AND IMPORTANCE: A patient with pituitary apoplexy resulting from
      lymphocytic adenohypophysitis, which caused visual disturbance during pregnancy,
      is described. This is the first report of such case. CLINICAL PRESENTATION: A 23
      year-old primigravida in her 25th week of gestation experienced headache and
      bitemporal hemianopsia of sudden onset. Magnetic resonance imaging (MRI) revealed
      a large pituitary mass with intratumoral hemorrhage. Although conservative
      treatment with intravenous glycerol improved the symptoms partially, the visual
      symptoms worsened again 6 weeks later. After delivering a girl by scheduled
      caesarean section her visual symptoms improved. Despite the symptomatic
      improvement, MRI showed the chiasmatic compression by the enlarged pituitary
      gland had not changed. Therefore, trans-sphenoidal surgery to decompress the
      chiasm was performed. Necrotic tissue was seen exuding behind the enlarged
      pituitary gland and adenohypophysitis with bleeding (apoplexy) was diagnosed
      histologically. After follow-up for 40 months, she was doing well without any
      visual or neurological deficits. CONCLUSION: Although relatively rare, pituitary
      apoplexy as a consequence of lymphocytic adenohypophysitis should be borne in
      mind when a pregnant woman presents with headache and visual disturbance of
      sudden onset.

PMID- 15949238
TI  - Secondary spinal cord hypoperfusion of circumscribed areas after injury in rats.
AB  - OBJECTIVES: The evaluation of the spatial spread of ischemia following spinal
      cord injury (SCI) is important for planning therapeutic strategies for secondary
      injury. The purpose of this study was to investigate in detail the change in
      regional spinal cord blood flow (rSCBF) after SCI. METHODS: Thirty-four male
      Wistar rats were used, for which laminectomies of the T11-13 vertebrae were
      performed. SCI was produced by a directed impact through a laminectomy site at
      the level of the Th12 using a pneumatic impact device. We measured the sequential
      and spatial changes of rSCBF using a laser Doppler scanning technique before and
      after SCI in rats not only at the injured myelomere but also at the circumferent
      myelomeres. SCBF mapping was carried out before and after SCI on each site.
      RESULTS: After SCI, the rSCBF value gradually decreased for each site for the SCI
      group (n=26), while it globally decreased at the epicenter. Moreover, a decrease
      in SCBF was observed at the caudal and rostral sites. The mean value of the %SCBF
      120 minutes after SCI for each site was 63.6+/-2.3% (Th11), 74.4+/-4.5% (Th12),
      75.8+/-3.2% (Th13), and was significantly lower for the rostral site compared
      with the caudal site (p<0.05, one-way analysis of variance). DISCUSSION: This
      study found that SCBF is significantly decreased not only at the injured
      myelomere but also at the circumferent myelomeres. Circumferentially extending
      ischemia after SCI is related to secondary injury after SCI. The improvement in
      SCBF after SCI, therefore, can be attributed to the treatment of SCI.

PMID- 15949239
TI  - Absence of nigrostriatal degeneration in LEC rats up to 20 weeks of age.
AB  - BACKGROUND: Long-Evans Cinnamon (LEC) rat has a genetic defect of copper
      metabolism that is similar to human Wilson's disease. We studied the pathological
      changes in the nigrostriatal system of the LEC rat to examine the feasibility of
      using the LEC rat as a model of neurological Wilson's disease. METHODS: LEC and
      Long-Evans Agouti (LEA) rats were killed at 12 and 20 weeks of age. FluoroJade B
      staining and immunohistochemistry were performed and Western blot compared the
      amount of tyrosine hydroxylase (TH) protein. RESULTS: Degenerating neurons were
      not found in the substantia nigra (SN) and striatum. Dopaminergic neurons were of
      the same number in the SN of both LEC and LEA rats. Gliosis was of a similar
      degree in both animals. Western blot showed the same amount of TH protein in both
      animals. DISCUSSION: There was no evidence of neurodegeneration in the
      nigrostriatal system of the LEC rat up to developmental age 20 weeks. The LEC rat
      is not a suitable model for deposition of copper in the brain in human Wilson's
      disease.

PMID- 15949240
TI  - Effects of conditioning peripheral repetitive magnetic stimulation in patients
      with complex regional pain syndrome.
AB  - OBJECTIVES: We tested whether repetitive magnetic stimulation (rMS) induces an
      afferent input to the spinocerebral tract in patients with complex regional pain
      syndrome (CRPS). METHODS: Cortical and spinal motor evoked potentials (cMEP and
      sMEP), as well as the contra- and ipsilateral silent period (cCSP and iCSP), were
      recorded in patients with CRPS type I before and after conditioning rMS, applied
      at cervical nerve roots innervating affected muscles. Patients were compared with
      a group of healthy subjects. RESULTS: In the group of patients we found that cMEP
      amplitudes were always significantly smaller for both hemispheres. In the group
      of healthy subjects we found a significant prolongation of the cCSP and iCSP
      after rMS. This was absent in patients. SMEP were always unchanged in both
      groups. DISCUSSION: This led us to the explanation that the afferent input to the
      motor cortical system in CRPS patients is less effective than in healthy
      subjects.

PMID- 15949241
TI  - Cerebral salt wasting syndrome in patients with aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: Hydroelectrolytic disturbances are part of the complications of
      subarachnoid hemorrhage. Cerebral salt wasting syndrome (CSWS) must be considered
      when hyponatremia is associated with a decrease in circulating volume. We
      performed this study to determine the clinical characteristics and management
      paradigm of patients with serum sodium concentration abnormalities and
      aneurysmatic subarachnoid hemorrhage. METHODS: We analyzed retrospectively
      clinical and laboratory data from eight patients with subarachnoid hemorrhage due
      to rupture of an intracranial saccular aneurysm and cerebral salt wasting
      syndrome. Their course, as well as their clinical findings and treatment, are
      described. RESULTS: In eight patients, hyponatremia that lasted for more than 24
      hours was detected (serum sodium under 135 mEq/l). The sodium disturbance
      occurred between day 3 and day 10 in all cases, in six of them in day 7 or day 8.
      The specific treatment for CSWS was to increase volume delivery according to the
      characteristics of the patient. Except for one case, none of the remaining
      patients required more than 72 hours of treatment to correct hyponatremia. No
      treatment-related complications were found CONCLUSION: Cerebral salt wasting
      syndrome, occurring in some patients with subarachnoid hemorrhage, is more
      commonly related to certain specific anatomic locations of the ruptured aneurysm,
      responds to sodium replacement therapy and fluids and can be diagnosed and
      treated based on the clinical, hydroelectrolytic and hemodynamic course of the
      patient. Further studies are needed to define the underlying mechanism of this
      condition.

PMID- 15949242
TI  - Effect of basic fibroblast growth factor on cultured rat neural stem cell in
      three-dimensional collagen gel.
AB  - OBJECTIVES: The effect of growth factors on the three-dimensional culture of
      neural stem cells has not been reported. We studied the effect of basic
      fibroblast growth factor (bFGF) on cultured rat neural stem cells in a three
      dimensional culture. METHODS: We cultured rat neural stem cells in collagen gel
      matrix for three-dimensional culture and examined the effect of bFGF under such
      culture conditions. RESULTS: After 4 days culture, the cell density in the bFGF
      treatment group was 12 times that of the non-treatment group, reaching a
      significantly high value. In the bFGF treatment group, microtubule associate
      protein (MAP)-2-positive cell aggregation occurred, although in the bFGF non
      treatment group there was no MAP-2-positive cell aggregation and few of the cells
      were sparsely distributed. Also, in the bFGF treatment group, MAP-2-positive cell
      aggregation had a luminal structure similar to neural rosettes. There was
      elongation of MAP-2-positive neurites from the cell aggregation to the
      circumference in the bFGF treatment group. DISCUSSION: bFGF is known to induce
      the proliferation, but not the differentiation of neural stem cells in two
      dimensional cultures. However, in the three-dimensional culture, bFGF induced
      both the proliferation and differentiation of neural stem cells. The three
      dimensional culture is, therefore, considered a useful method for predicting the
      response of neural stem cells to cytokines or biologically active substances in
      vivo.

PMID- 15949243
TI  - Changes in hemodynamics during isoflurane and propofol anesthesia: a comparison
      study.
AB  - OBJECTIVES: Volatile anesthetics are thought to impair cerebral autoregulation
      more than i.v. anesthetics. However, few comparative studies have been carried
      out in humans. The aim of our study was to evaluate the differences in cerebral
      hemodynamic changes after introduction of isoflurane (a volatile anesthetic) and
      propofol (an i.v. anesthetic). METHODS: Eighteen consecutive patients submitted
      to laparoscopic cholecystectomy were selected. After the induction, anesthesia
      was maintained by isoflurane (one minimum alveolar anesthetic concentration)
      during the first part of the surgical operation, and then by propofol (5
      mg/kg/hour i.v.). Ventilation was adjusted to maintain a constant end-tidal
      CO(2). Middle artery flow velocity was assessed by means of transcranial Doppler
      ultrasonography. Arterial blood pressure, heart rate (HR), capnometry, pulse
      oxymetry, inspired fraction of O(2), and body temperature, were monitored.
      RESULTS: Cerebral artery velocity, HR, and mean arterial pressure all
      significantly increased from baseline after the introduction of isoflurane
      (p<0.05); the HR and mean arterial blood pressure showed no significant
      difference between the isoflurane and propofol phases. Isoflurane anesthesia
      induced a significant increase in cerebral blood velocity. Propofol introduction
      led to a significant decrease in cerebral artery velocity (p<0.05). CONCLUSIONS:
      Propofol but not isoflurane decreased cerebral blood velocity thus restoring
      cerebral autoregulation and the coupling between cerebral blood flow and cerebral
      metabolism.

PMID- 15949244
TI  - Age-related changes in the distribution of Kv1.1 and Kv3.1 in rat cochlear
      nuclei.
AB  - OBJECTIVES: To identify age-related changes in voltage-gated K(+) (Kv) channels
      that contribute to temporal processing in neurons of the central auditory system,
      we investigated the distribution of Kv1.1 and Kv3.1 in the auditory brainstem of
      adult and aged rats. METHODS: Immunohistochemistry was performed in accordance
      with the free-floating method described earlier. RESULTS: Among the auditory
      nuclei, only the posterior ventral cochlear nucleus (PVCN) showed age-related
      changes. Kv1.1 immunoreactivity was increased in the octopus cell bodies, while
      the staining intensity was significantly decreased in the neuropil. Image
      analysis demonstrated the specific increase in Kv1.1 immunoreactivity in aged
      cochlear nucleus neurons although the mean density of the entire selection was
      significantly decreased. In contrast, the number of Kv1.1-immunoreactive neurons
      was not significantly different between control and aged groups. The
      immunoreactivity for Kv3.1 was decreased in the octopus cells and neuropil of
      aged PVCN, which was confirmed by image analysis. The number of Kv3.1-positive
      cells was also significantly decreased in aged PVCN. DISCUSSION: This study may
      provide useful data to compare age-related changes in Kv1.1 and Kv3.1 with known
      physiological properties of auditory neurons.

PMID- 15949245
TI  - Extent of spontaneous cross-flow via the anterior communicating artery in steno
      occlusive carotid artery disease.
AB  - PURPOSE: Our purpose was to evaluate the agreement of transcranial color-coded
      duplex sonography (TCCS) measurements and intra-arterial digital subtraction
      angiography (DSA) findings in determining the extent of spontaneous cross-flow
      via the anterior communicating artery (AcoA) in patients with internal carotid
      artery (ICA) stenosis. METHODS: Thirty adult patients with suspected uni- or
      bilateral high-grade carotid artery stenosis were prospectively examined by DSA
      and angle-corrected TCCS. The extent of cross-flow was determined considering
      retrograde flow in the ipsilateral anterior cerebral artery (ACA) and sideto-side
      differences of the A1-segments of the ACA and middle cerebral arteries (MCAs) by
      both techniques. Cross-flow was angiographically categorized by means of a four
      step scale. DSA findings were correlated with side-to-side differences in mean
      blood flow velocity as well as flow direction measured by TCCS. RESULTS: Twenty
      seven of 30 patients had a uni- or bilateral ICA stenosis of >49%. Excellent
      agreement between TCCS and DSA was evaluated for the detection of lack (grades 0
      and 1) or presence (grades 2 and 3) of reversed flow in the ACA (sensitivity
      100%, specificity 93%, positive predictive value 94%). Post hoc analysis of the
      mean velocities in the ACA and MCA revealed a side-to-side difference of 25 cm/s
      as a cutting point allowing for definition of a corresponding four-grade scale
      for ultrasound. However, full agreement, i.e.same grade of cross-flow detected by
      both techniques, was only found in 17(57%) of 30 cases. CONCLUSIONS: Non-invasive
      TCCS is reliable for detecting reversed flow in the ACA in patients with ICA
      stenosis. However, there is only a moderate agreement between angiography and
      TCCS in quantifying the extent of spontaneous anterior cross-flow because
      different information on the intracranial hemodynamics may be obtained.

PMID- 15949246
TI  - Inhibitory effect of deuterium oxide on cerebral vasospasm after experimental
      subarachnoid hemorrhage in a rabbit model.
AB  - OBJECT: We wished to determine the inhibitory effect of deuterium oxide (D(2)O)
      on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH). METHODS AND
      RESULTS: An established rabbit single-hemorrhage was used. Thirty-five rabbits
      were randomly divided into four groups: non-treatment, sham control, lower-D(2)O,
      and higher-D(2)O treatment groups. Angiography was performed before (day 0) and
      after (day 2) SAH and the CVS ratio was calculated by comparing the diameter of
      the basilar artery (BA) on day 2 with that on day 0. After death, blood clot
      volume was assessed and the BA was dissected from the brain for histological
      examination. The CVS ratio in D(2)O-treatment groups was significantly higher in
      comparison with that in non-treatment and sham control groups (p < 0.0001).
      Furthermore, the volume of blood clot around the BA was reduced significantly in
      D(2)O-treatment groups, compared with those in both the non-treatment and the
      sham control groups (p < 0.05). Histological examination showed that the BA
      represented less folding of the internal elastic lumina in D(2)O-treatment
      groups, while a corrugation of the intima with the thickened vessel wall was seen
      in both the non-treatment and sham control groups. CONCLUSION: Therapeutic
      administration of D(2)O into the cisterna magna exhibited an inhibitory effect on
      CVS after SAH in rabbits.

PMID- 15949247
TI  - The relation between serum levels of osteoprotegerin and postoperative epidural
      fibrosis in patients who underwent surgery for lumbar disc herniation.
AB  - OBJECTIVES: Epidural fibrosis (EF) is a part of the normal physiological tissue
      response to laminectomy and it is an important cause of failed back surgery
      syndrome (FBSS). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis
      factor receptor family, and is expressed in high concentrations by a variety of
      tissues and cell types. The objective of this study was to evaluate the
      relationship between serum OPG levels, and the existence of postoperative EF in
      patients with lumbar disc herniation. It has been suggested that cytokines and
      growth factors, which play a role in the wound healing, may enhance the
      expression of OPG. METHODS: Forty women who underwent surgery for lumbar disc
      herniation were included in this study. Postoperative MRI was performed to assess
      EF in all patients. RESULTS: The serum OPG levels of subjects with postoperative
      EF were significantly higher than those of subjects without postoperative EF
      (4.72 +/- 0.27 versus 3.25 +/-0.41 pmol/l; p=0.005) DISCUSSION: Although the role
      of OPG in the development of EF is poorly understood, our results suggest that
      elevated levels of serum OPG are associated with and may play a role in the
      pathogenesis of fibrotic process.

PMID- 15949248
TI  - Interview with Dr. George Zarb.

PMID- 15949249
TI  - A tribute to Dr. George Zarb.

PMID- 15949250
TI  - Prosthodontics: a past with a future?
AB  - As one of the oldest dental specialties, prosthodontics has a long history of
      innovation and adaptability. This overview of the field presents landmarks in the
      development of prosthodontics from mediaeval times to the present and speculates
      on some future trends. It effectively sets the stage for the other articles in
      this issue, which explore the many facets of prosthodontic evolution.

PMID- 15949251
TI  - The impact of oral implants - past and future, 1966-2042.
AB  - This paper traces the history of oral implants, beginning with their early
      undocumented use in the mid-1960s. Although early experimentation with the
      Branemark system of osseointegration was unsuccessful, significant improvements
      and scrupulous documentation of the 1970s led to their general acceptance. George
      Zarb spearheaded their introduction into North America and application of the
      osseointegration technique soon expanded to extraoral craniofacial prostheses and
      bone-anchored hearing aids.New possibilities, such as altered surface properties
      and the use of implants in grafted and irradiated bone are currently being
      explored, although commercial pressure to introduce new products before they are
      adequately tested is a cause for concern. The future will see bioactive surfaces
      and additives that stimulate bone growth. In fact, with the possibility of in
      vivo growth of new teeth, implants may become unnecessary.

PMID- 15949252
TI  - Changes in the prosthodontic literature 1966 to 2042.
AB  - PURPOSE: To describe the growth and content of the prosthodontic literature over
      the last 4 decades, to make a prognosis on its probable development in the coming
      4 decades and to discuss changes in the content of the International Journal of
      Prosthodontics (IJP) from its start in 1988 to 2004. METHODS: MEDLINE was
      searched for articles on prosthodontics published between 1966 and April 2004.
      All volumes of IJP were examined with respect to type, subject area and
      geographic origin of articles. RESULTS: Using the term "prosthodontics," the
      MEDLINE search produced 66,600 hits. The proportion of clinical studies increased
      from 1% during the first 10-year period to 13% since 2001. Articles on removable
      dentures decreased during the period reviewed, whereas those on implant
      prosthodontics increased. Randomized controlled trials were rare and often of
      inadequate quality. Literature reviews have become popular, but many do not
      follow current guidelines for systematic reviews. A marked change in geographic
      origin of articles in IJP has occurred, with a decrease in material from North
      America and an increase in that from Europe and Asia. The Internet and open
      access publishing will probably have a great impact on the future development of
      the prosthodontic literature. CONCLUSIONS: Substantial changes have occurred in
      the prosthodontic literature between 1966 and 2004, and they can be expected to
      continue with the rapid development of information technology and increased use
      of the Internet.

PMID- 15949253
TI  - Prosthodontics 1966-2042: changes in prosthodontic education, past and future.
AB  - Past changes in prosthodontic education have been influenced by educators"
      understanding of learning, the physical plants in which they teach and the
      evolution of the profession (both clinically and politically). A 1968 survey
      illustrates an emphasis on materials and techniques, and the literature of the
      day respected "expert" opinion. Although the need for prosthodontics was expected
      to decline with the promotion of preventive measures, it is actually increasing
      with the aging population. Organizational support for defining the specialty of
      prosthodontics to encompass a broad spectrum of dental restorations and related
      care helped develop commitment to improved research and education. Instrumental
      in these improvements were faculty with advanced education in the discipline,
      better physical plants in which to work and an understanding of the theories of
      teaching and learning. Faculty will continue to be innovative and adopt new
      approaches such as evidence-based dentistry and problem-based learning. However,
      the lure of research funding and institutional expectations will probably
      influence how faculty spend their time and energy. Prosthodontic education will
      continue to evolve, but it will be influenced by its institutional and
      professional environments.

PMID- 15949254
TI  - The changing relations between the allied disciplines.
AB  - Relations between the allied disciplines of prosthodontics, oral and
      maxillofacial surgery and periodontics over the last 30 years are reviewed,
      together with the development of clinical activity progressing from the
      preosseointegration era to the present day. New developments are foreseen in the
      coming 30 years.

PMID- 15949255
TI  - A look at the (near) future based on the (recent) past - how our patients have
      changed and how they will change.
AB  - Remedies for dental diseases have been in use for as long as 4,000 years, and
      various materials and methods have been used over the millennia. Dentistry
      continues to change in response to changes in the age distribution, origins,
      financial means and health of the population, as well as to changes within the
      profession itself. The Canadian population is very unevenly distributed
      geographically and ethnically. Furthermore, it is aging rapidly and life
      expectancy is increasing. Although the average income of Canadians has increased,
      the increase was unevenly distributed, and the gap between rich and poor
      continues to expand. There has been a steady rise in the number of Canadians with
      dental insurance, although the proportion of the population with insurance varies
      from one province to another. Not surprisingly, people with dental insurance
      compared to those without are more frequent users of dental services. The rate of
      caries attack has diminished in industrialized countries, but people are keeping
      their teeth longer, so caries will remain a significant public health problem,
      particularly among elderly people. In addition, smoking tobacco is strongly
      associated with periodontal disease; thus, there should be more action within the
      dental community in support of smoking cessation programs. The composition of the
      dental care community is also changing. The ratios of dentists and dental
      hygienists to the population have increased, the services offered by dental
      technicians have expanded greatly, and the services offered by denturists have
      also increased as these services gain more widespread acceptance. Use of dental
      services in Canada remains reasonably broad; however, denture-wearers continue to
      regard uncomfortable dentures as a normal part of aging. The pattern of uneven
      distribution of disease and access to service remains the major challenge facing
      the dental profession.

PMID- 15949256
TI  - Prosthodontic research: breaking traditional barriers.
AB  - There is considerable concern among leaders in both academia and the
      prosthodontic profession about the vitality of prosthodontic research and the
      discipline in general. Many feel that prosthodontics should be focused more on
      issues of societal significance. In addition, patient-oriented research is
      becoming more difficult to support within the current climate of ever-lower
      priority for discipline-based research.A break with traditional lines of enquiry
      is required, which will entail a corresponding break with established
      departmental boundaries, to gain access to a multiplicity of complementary
      skills. Several themes will be crucial in future prosthodontic research: clinical
      decision making, including health economics; materials science and host response
      at the implant interface; biocompatibility, functional properties and
      serviceability of prosthodontic materials; and function and dysfunction of the
      masticatory system. These themes are at the core of future projects that will
      address quality-of-life issues related to tooth loss. Prosthodontic researchers
      will have to be far more aggressive in developing synergistic collaborative
      arrangements, to align prosthodontic research with the major issues of the day,
      such as aging of the population, health disparities and access to preventive
      strategies. Through these collaborations, prosthodontics will remain a flagship
      discipline within dentistry, and its practitioners will be engaged in the major
      issues of health care.

PMID- 15949257
TI  - [The outcome analysis of different treatment regimens in 206 patients with
      multiple myeloma].
AB  - OBJECTIVE: To analyse the outcome of different regimens for the treatment of
      patients with multiple myeloma (MM). METHODS: Response rate, median survival time
      and overall survival rate of 206 MM patients treated with different protocols
      were retrospectively analysed. RESULT: The median survival time, 3- and 5-year
      overall survival (OS) of 200 MM patients treated with conventional therapy were
      30.5 months, 32.0% and 15.8%, respectively. The total response rate and complete
      response (CR) rate of 195 patients treated with MP regimen and combination
      chemotherapy (CCT) were 45.6% and 14.9%, respectively. The response rates were
      higher for the patients treated with CCT than for those treated with MP (50.3%
      versus 30.4%, P < 0.05). The median survival time, 3- and 5- year OS in MP versus
      CCT group were 30.0 versus 30.5 months, 22.0% versus 35.0%, 13.2% versus 16.7%,
      respectively, but all of them have no statistical difference. Compared with those
      without IFN alpha maintenance therapy, patients received IFN alpha therapy showed
      a higher response rate (34.4% versus 53.6%, P < 0.05) and a longer median
      survival time (27 versus 52 months, P < 0.01). The total response in patients
      received thalidomide was 65.5%. Of the 6 patients received hematopoietic stem
      cell transplantation (HSCT), 5 remained alive in CR or PR with a mean survival
      time of (73.0 +/- 12.5) months. CONCLUSIONS: CCT yields higher response rates,
      but not longer survival time than MP does for the treatment of MM. The response
      rate as well as the overall survival rate increased when IFN alpha was used as
      maintenance therapy. Thalidomide can improve response rate as well. HSCT could
      prolong survival time in patients aged < 60 years with good status.

PMID- 15949258
TI  - [Effect of 2-methoxyestradiol on cell differentiation of myeloma cell line CZ-1].
AB  - OBJECTIVE: To investigate the differentiation induction effect of 2
      methoxyestradiol (2ME2), an estrogen derivative on myeloma cell line CZ-1.
      METHODS: The changes of CZ-1 cells in morphology, expression of surface CD49e and
      quantity of light chain secretion in the supernatant were observed when treated
      with 0.1 approximately 0.5 micromol/L 2ME2 for 48 h. RESULTS: 2ME2 could induce
      differentiation of CZ-1 cells. The cells appeared decreased in size of nucleus,
      increased in cytoplasma, decreased in the ratio of nucleus to plasma, decreased
      in number or disappearance of nucleolus, and thickness and pyknosis of chromatin.
      The expression of CD49e was increased from (12.20 +/- 1.57)% to (24.80 +/- 1.26)%
      (P < 0.05). Light chain secretion in the supernatant was increased from (35.97 +/
      2.60) microg/ml to (79.67 +/- 1.88) microg/ml (P < 0.05). CONCLUSION: Low
      concentrations of 2ME2 could induce differentiation of myeloma cell line CZ-1.

PMID- 15949259
TI  - [Investigation of the effect of 2-methoxyestradiol and arsenic trioxide on the
      apoptosis-associated gene expression profile of myeloma cells].
AB  - OBJECTIVE: To explore the effect of 2-methoxyestradiol (2ME2) and arsenic
      trioxide (As2O3) on the apoptosis related gene expression in multiple myeloma
      cell line CZ-1. METHODS: Total RNA was isolated from CZ-1 cells which had been
      treated with 2ME2 and As2O3 at an apoptosis-inducing concentration and reverse
      transcribed into a cDNA probe labeled with Bio-16-dUTP, and then hybridized it
      with a microarray containing up to 96 key genes involved in apoptosis. The gene
      expression profile of the 2ME2 and As2O3 treated CZ-1 cells were analyzed with
      GEArray Analyzer software. The microarray results were confirmed by RT-PCR.
      RESULTS: As2O3 treatment caused the alteration in the expression of 52 genes
      (54.2% of total genes on microarray). Among them, 42 (80.8%) were upregulated and
      10 (19.2%) were downregulated. The upregulated genes were mainly involved in
      caspases family, P53 and ATM pathway, death effector domain family, TNF receptor
      family and CIDE family. 2ME2 treatment resulted in the alteration of 42 genes
      (43.8% of the total genes on microarray). Of them, 32 (76.2%) were downregulated
      and 10 (23.8%) were upregulated. The downregulated genes mainly belonged to bcl-2
      family, inhibitor of apoptosis protein family (IAP), TRAF family, TNF ligand
      family, and CARD family. CONCLUSION: 2ME2 and As2O3 induce the CZ-1 cells
      apoptosis by different pathways. As2O3 mainly induces upregulation of
      proapoptotic genes, and 2ME2 downregulation of anti-apoptotic genes expression.

PMID- 15949260
TI  - [Study of anti-myeloma activity of interleukin-2 activated bone marrow in vitro].
AB  - OBJECTIVE: To study the anti-myeloma activity of interleukin-2 activated bone
      marrow (ABM). METHODS: Bone marrow mononuclear cells (BMMNC) from multiple
      myeloma and iron-deficiency anemia patients were cultured in the presence of rIL
      2. The anti-myeloma activity of ABM against U266 cells, cells expressing surface
      CD45, CD38, CD138, the levels of TNF-alpha and IFN-gamma in ABM culture
      supernatant were measured with MTT method, flow cytometry and ELISA method
      respectively after bone marrow was activated with rIL-2 for 24 and 72 hours.
      RESULTS: The tumor-killing activities against U266 cells of ABM were
      significantly increased compared with that of non-activated bone marrow (NBM) at
      72 hours [(69.70 +/- 26.57)% vs (43.20 +/- 12.39)%, P < 0.05] and 24 hours
      [(34.25 +/- 11.93)% vs (26.53 +/- 5.48)%]. The CD45(-)CD38(+)CD138(+) cells of
      ABM from myeloma group at 72 hours were decreased from (8.46 +/- 3.66)% to (4.79
      +/- 1.56)% (P < 0.05). TNF-alpha and IFN-gamma were detectable after cultured for
      24 hours in both normal control group and myeloma group and went higher at 72
      hours. The level of TNF-alpha and IFN-gamma were significantly increased in ABM
      compared with that in NBM (P < 0.05). Meanwhile, there was a positive
      relationship between the level of TNF-alpha, IFN-gamma and cytotoxicity of ABM
      from normal control group at 24 hours and 72 hours (P < 0.05), and was a negative
      relationship between TNF-alpha and IFN-gamma levels and the CD45(
      )CD38(+)CD138(+) cells in myeloma group at 72 hours (P < 0.05). CONCLUSION:
      Normal BMMNCs activated with rIL-2 have tumor-killing activities against U266
      cells. Myeloma cells and tumor burden were decreased in myeloma bone marrow after
      the marrow was activated with rIL-2. Production of TNF-alpha and IFN-gamma from
      bone marrow cells including T cells, monocyte-macrophages and NK cells activated
      with rIL-2 might be involved in anti-myeloma activity of ABM.

PMID- 15949261
TI  - [Detection of gene expression alteration of myeloma cells treated with arsenic
      trioxide].
AB  - OBJECTIVE: To investigate the effect of arsenic trioxide on multiple myeloma (MM)
      cell gene expression and explore the molecular mechanism of arsenic trioxide
      therapy for MM. METHODS: U266 cells were divided into two groups, group A as
      control group and group B as test group. Cells were cultured for 48 hours, and
      total RNA and mRNA were extracted. Suppression subtractive hybridization (SSHs)
      was performed to distinguish the differentially expressed genes. The products
      were cloned into pGEM-T Easy Vector, and transfected into the competent host
      JM109 to construct two subtractive libraries. Positive colonies were selected by
      blue-white screening, and the plasmids were extracted. Homologous comparison was
      conducted in GenBank. RESULTS: Five downregulated clones were isolated in the
      first SSH: (1) Aminopeptidase N, (2) Homosapiens tumor translationally-controlled
      protein 1, (3) Human ATP synthetase A chain, (4) Signal recognition particle A10,
      (5) Mitochondrial ATP synthetase/ATPase subunit 6. Four upregulated clones were
      isolated in the second SSH: (1) Calcium-binding protein A10, (2) Keratin 6A, (3)
      45 kD MIP repetitive element containing splicing factor and (4) poly(A)-binding
      protein. CONCLUSIONS: Arsenic trioxide exerts proliferation inhibition and
      apoptosis induction on MM cells by regulating genes expression.

PMID- 15949263
TI  - [Study of TRAIL receptors expression on the mononuclear cells from multiple
      myeloma patients and KM3 cells].
AB  - OBJECTIVE: To study the differential expression of four TRAIL receptors on bone
      marrow mononuclear cells (BMMNC) from multiple myeloma (MM) patients and myeloma
      cell line KM3 cells, to compare their altered expressions after chemotherapy and
      to explore the mechanisms by which TRAIL selectively kills tumor cells. METHODS:
      Semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and
      flow cytometry were used to investigate the expression of four TRAIL receptors on
      BMMNCs in 23 MM patients, KM3 cells and 15 controls, and the changes of their
      expression pattern after chemotherapy and after incubation of KM3 cells with sub
      clinical concentration of doxorubicin. RESULTS: DR4 and DR5 were highly expressed
      on KM3 cells with no expression of DcR1 and DcR2. Expressions of DR4 and DR5 on
      BMMNCs from MM patients were higher and expression of DcR1 and DcR2 were lower
      than that of controls (P < 0.05). The expression of DR5 on MM and KM3 cells was
      up-regulated after chemotherapy and exposure to doxorubicin (P < 0. 05).
      CONCLUSIONS: The expressions of four TRAIL receptors on myeloma cells and normal
      controls were different, which might account for the selective killing effect of
      TRAIL on MM cells. Up-regulated DR5 on KM3 cells after incubating with
      doxorubicin and after chemotherapy suggests the cytotoxic agents might enhance
      the apoptosis of MM cells.

PMID- 15949264
TI  - [A clinicopathological study of 96 cases of lymphoblastic lymphoma].
AB  - OBJECTIVE: To investigate the clinicopathological and immunohistochemical
      features of lymphoblastic lymphoma (LBL). METHODS: A retrospective
      clinicopathological study of 96 cases LBL was carried out. Immunohistochemical
      staining was used for the characterization and immunophenotyping. RESULTS: The
      patients age ranged from 4 to 72 years, with a median of 16 years, 69 patients
      were male and 27 female. Seventy-three cases had superficial or multi
      lymphoadenopathy and 31 of them had mediastinal masses. Bone marrow was involved
      in 15 cases. Seventy-three cases were in clinical stages III and IV. The median
      survival of the followed-up patients was 5.5 (2 approximately 120) months. TdT
      and CD99 positive reactions were 75.0% and 92.7%, respectively. Of the 96 cases,
      78 displayed T-cell marker positivity and 18 B-cell markers. 82.1% of the
      patients younger than 30 years of age had significantly higher incidences of T
      LBL (64 patients), and 93.6% of the patients with mediastinal masses expressed T
      cell markers. The poor prognostic factors were T-cell tumors, clinical stages III
      and IV, Ki-67 PI < 80% and no chemotherapy (P < 0.01). CONCLUSION: In children
      and young males, mediastinal masses with superficial or multi-lymphoadenopathy
      favors the diagnosis of LBL, but negative TdT reaction can not exclude this
      diagnosis. T-LBL is more common than B-LBL. Clinical stages, immunophenotypes and
      the level of Ki-67 expression were closely related with prognosis of LBL.

PMID- 15949265
TI  - [Prognostic analysis of 51 cases of primary nodal diffuse large B-cell
      lymphomas].
AB  - OBJECTIVE: To explore the prognostic factors of primary nodal diffuse large B
      cell lymphomas (N-DLBCL). METHODS: According to the 2001 WHO classification of
      tumors of hematopoietic and lymphoid tissue, 51 cases of primary N-DLBCL were
      collected for clinical data analysis and immunohistochemical assay. Antibodies
      used for study were anti-CD20, CD79alpha, CD45RO, CD3, Bcl-2, Ki-67, CD30, CD15,
      kappa, lambda, Cyclin D1, TdT, GFAP, CK, MPO. The survival data was analyzed.
      RESULTS: Of the 51 cases of N-DLBCLs, 40 were reclassified as centroblastic, 3 B
      immunoblastic, 1 T-cell/histiocytes rich, 2 B-cell anaplastic large cell, 1
      plasmablastic, and 4 unclassified. Expression of Bcl-2 oncoprotein was observed
      in 24 cases (47.1%). The median Ki-67 index was 50.0% and the index more than 40%
      was found in 35 cases (68.6%). Survival analysis of 35 cases had follow up data
      showed that the 2 year and 5-year overall survival (OS) rates were 48.54% and
      35.30%, respectively. The 5-year OS rates patients with International Prognosis
      Index (IPI) >/= 3 was lower than that with IPI < 3 (P < 0.01). The 5-year OS
      rates for patients with B symptoms was lower than that without B symptoms (P <
      0.05). The 5-year OS rates for patients with Ki-67 index more than 40% was lower
      than that with less than 40% (P < 0.05). The expression of Bcl-2 oncoprotein was
      uncorrelated to prognosis (P > 0.05). CONCLUSION: IPI, B symptoms and Ki-67 index
      are the prognostic factors for patients with N-DLBCL.

PMID- 15949266
TI  - [Effects of dexamethasone on arsenic trioxide induced apoptosis, NF-kappaB
      activation and gene expression in lymphoma cell line].
AB  - OBJECTIVES: To study the effect of dexamethasone (Dex) on the apoptosis and NF
      kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by
      As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on
      apoptosis. METHODS: Cell apoptosis was analysed by Annexin V. Fluctuation of NF
      kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry.
      RESULTS: The apoptosis and activation of NF-kappaB of Raji cells could be induced
      by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly
      increased (77.5%) the apoptosis induced by As2O3 (P < 0.05). Dex suppressed the
      activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P < 0.05).
      There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB.
      CONCLUSIONS: As2O3 could induce apoptosis, activate NF-kappaB and up-regulate
      expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by
      Dex may be related to suppressing activation of NF-kappaB and down-regulating
      expression of MMP9 and VEGF.

PMID- 15949268
TI  - [Interdigitating dendritic cell sarcoma-a case report with literature review].
AB  - OBJECTIVE: To report a case of interdigitating dendritic cell sarcoma (IDCS).
      PATIENT MATERIAL: The patient was a 41-year-old man with a lymph node bulging in
      the left neck. Laboratory examination of peripheral blood and bone marrow was
      abnormal. The diagnosis of IDCS was made by immunohistochemistry and electron
      microscopy. Treatment of this patient with ABVD regimen (adriamycin, bleomycin,
      vinblastine, dacarbazine) resulted in obvious improvement, but did not control
      the tumor infiltration. CONCLUSION: IDCS has no distinctive clinical or
      pathohistological characteristics. Immunohistochemistry and electron microscopy
      are crucial in distinguishing it from other histiocytic/dendritic cell neoplasms.
      IDCS displays an aggressive behaviour, and the responses to chemotherapy are
      variable.

PMID- 15949269
TI  - [The response of bone marrow hematopoietic cells to G-CSF in paroxysmal nocturnal
      hemoglobinuria patients].
AB  - OBJECTIVE: To study the response of hematopoietic cells (HSC) to granulocyte
      colony stimulating factor (G-CSF) in paroxysmal nocturnal hemoglobinuria (PNH)
      patients. METHODS: (1) Bone marrow mononuclear cells (BMMNC) from 17 PNH patients
      and 12 normal subjects were inoculated into semisolid culture media containing or
      not G-CSF (50 ng/ml). The cluster/colony forming unit-granulocyte/monocyte
      (CFU/cFU-GM) were counted and compared. (2) BMMNC of 20 PNH patients and 12
      normal controls were triply stained for CD34, CD59 and G-CSF receptor CD114/stem
      cell factor receptor (C-KIT) CD117 and assessed by FCM. The CD34(+) cells were
      identified as CD34(+)/CD59(+) and CD34(+)/CD59(-). Percentage of CD114 and CD117
      expression in each cell population was calculated. RESULTS: (1) PNH cFU-GM
      without G-CSF were (112.41 +/- 22.74)/10(5) BMMNC, while with G-CSF: (133.82 +/-
      25.85)/10(5) BMMNC and normal cFU-GM were (190.33 +/- 36.05)/10(5) BMMNC, (309.42
      +/- 92.94)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC
      formed less cFU-GM than control did, both of the two kinds of BMMNC responded to
      G-CSF well (P < 0.05), but the increment of PNH cFU-GM yields was less than that
      of the normal control (P < 0.05). CFU-GM yields of PNH BMMNC without G-CSF were
      (24.29 +/- 9.05)/10(5) BMMNC, with G-CSF were (27.53 +/- 10.65)/10(5) BMMNC,
      while normal control were (77.42 +/- 36.01)/10(5) BMMNC and (98.00 +/-
      43.14)/10(5) BMMNC, respectively. Whether with or without G-CSF, PNH BMMNC showed
      less CFU-GM yields than that of control (P < 0.05). (2) The percentage of CD114
      positive cells in PNH CD34(+)CD59(+) BMMNC was (73.34 +/- 29.40)% and that in PNH
      CD34(+)CD59(-) BMMNC and in control CD34(+)CD59(+) BMMNC were (32.70 +/- 6.89)%
      and (58.52 +/- 29.99)%, respectively. The percentage of CD114 expression in PNH
      CD34(+) CD59(-) BMMNC was less than that in the other two groups (P < 0.05). The
      percentages of CD117 positivities on the PNH CD34(+)CD59(+) BMMNC were (76.90 +/-
      22.08)%, PNH CD34(+) CD59(-) (36.03 +/- 7.69)% and control CD34(+) CD59(+) (80.28
      +/- 13.36)%, respectively (P < 0.01). CONCLUSION: In vitro, BMMNC of normal
      control grow better, and respond better to G-CSF than PNH BMMNC do. PNH
      CD34(+)CD59(-) BMMNC express less G-CSF receptor and C-KIT than PNH
      CD34(+)CD59(+) and normal CD34(+)CD59(+) BMMNC do, which may be the reason that
      abnormal PNH clone grow worse than the normal clones do.

PMID- 15949270
TI  - [The clinical features of hepatitis associated aplastic anemia].
AB  - OBJECTIVE: To analyse the proportion of hepatitis associated aplastic anemia
      (HAAA) in severe aplastic anemia (SAA) and its clinical features of HAAA.
      METHODS: All newly diagnosed SAA cases in our department in the recent 5 years
      were analyzed. A case-control study was undertaken to investigate the differences
      of clinical and laboratory features between HAAA and non-hepatitis associated SAA
      (non-HASAA) patients. RESULTS: The proportion of HAAA in SAA was 3.3%. There was
      no significant difference in PB cell counts, bone marrow hematopoiesis status and
      the amount of blood transfusion between HAAA and non-HASAA patients. Sera from 13
      patients with HAAA were tested for antibodies to hepatitis viruses A, B, and C
      and hepatitis B surface antigen. Twelve (92.3%) of them had negative serologic
      results for the tests and only one (7.7%) had a positive result for HBsAg and
      HBeAg. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      levels were decreased prior to the diagnosis in twelve (92.3%) of the 13 HAAA
      patients. The percentage of CD4(+) cells in HAAA patients was significantly lower
      than that in non-HASAA patients (P < 0.05). HAAA patients had higher percentages
      of CD8(+) cells (P < 0.05) and lower ratios of CD4(+)/CD8(+) (P < 0.05). The
      early infection rate of the HAAA patients was significantly higher than that of
      non-HASAA patients (84.6% vs 42.3%, P < 0.05), with different mortalities (61.5%
      vs 15.4%, P < 0.05). The 2-year survival rate of HAAA patients was significantly
      lower than that of non-HASAA patients (16.6% vs 83.2%, P < 0.01). CONCLUSION: The
      proportion of HAAA in SAA was 3.3%. Most of HAAA were associated with non-A, non
      B and non-C hepatitis virus. Compared with that of non-HASAA, the abnormality of
      T cell immunity of HAAA was more severe, with a higher frequency of early
      infection and a higher mortality rate.

PMID- 15949281
TI  - [Karyotyping and immunophenotyping analyses of the CD34+ CD38- cells isolated
      from human umbilical cord blood].
AB  - OBJECTIVE: To cultivate hematopoietic stem/progenitor cells (CD34(+)CD38(-))
      isolated from umbilical cord blood (UCB) long for the observation of cell growth
      and expansion in vitro, surface marker expression, and chromosomal complements.
      METHODS: By flow cytometry CD34-FITC and CD38-PE labeled CD34(+) and CD38(-)
      stem/progenitor cells were isolated from UCB. The cells were cultivated in vitro
      for 6 months in a stem cell culture system with addition of six kinds of cell
      growth factors (IL-3, IL-6, GM-CSF, Epo, SCF, IGF-1). One month after
      cultivation, cultured cells were investigated for surface marker expression by
      flow cytometry and karyotype by G banding method. RESULTS: After 7-12 days
      cultivation, the CD34(+)CD38(-) stem/progenitor cells began proliferation. The
      proliferation rate and the peak proliferation duration were greater in 1
      cell/well cultivation conditions than in 10 cells/well. The cells remained
      CD34(+)CD38(-) and their karyotypic characteristics remained unchanged.
      CONCLUSION: CD34(+)CD38(-) stem/progenitor cells from UCB may provide a larger
      than original amount of stem/progenitor cells for transplantation after long-term
      cultivation in vitro.

PMID- 15949283
TI  - [Intra-bone marrow cavity transplantation of human umbilical cord blood
      mononuclear cells into NOD/SCID mice].
AB  - OBJECTIVE: To evaluate the hematopoietic reconstitution of implanted NOD/SCID
      mice, after intra-bone marrow cavity injection (iBM) of human umbilical cord
      blood (CB) mononuclear cells (MNCs). METHODS: 24 female NOD/SCID mice were
      divided into different MNCs dosage iBM groups (3 x 10(6), 1 x 10(7), 3 x 10(7)
      cells), tail vein intravenous injection (iTV) group (3 x 10(7) cells) and control
      group (iBM of medium only). CB MNCs sorted by Ficoll-Hypaque were transplanted
      into left tibia bone marrow cavity of 6- to 8-week-old NOD/SCID mice, which were
      anesthetized and sublethally irradiated (270 cGy (137)Cs-gamma irradiation). The
      distribution of injected CB MNCs in noninjected right tibia of the same implanted
      mice was observed 24 hours after iBM. The establishment of hematopoiesis and the
      survival of mice were observed. BM cell surface CD marker expressions, dye Dil-CM
      tracing and human beta-actin from implanted mice were assessed 8 weeks after iBM
      or iTV. RESULTS: Dil-CM marker could be detected on BM cells from noninjected
      right tibia 24 hours after iBM. Fourteen engrafted mice survived at the end of
      our study. Among them two, four and five were of iBM-1, iBM-2 and iBM-3 groups
      respectively, and one of control group and two of iTV group. White blood cell
      reconstitution was better in iBM mice than in iTV and control mice. There were
      human markers including CD45, Dil-CM and beta-actin DNA in the marrow cells from
      the human CB MNC engrafted mice. CONCLUSION: The preliminary results showed that
      hematopoiesis reconstitution by iBM was significantly better than iTV.

PMID- 15949284
TI  - [Up-regulation of costimulatory molecules by sodium butyrate in acute leukemia
      cells and its molecular mechanism].
AB  - OBJECTIVE: To explore the effect of sodium butyrate (SB) on the expression of
      costimulatory molecules in acute leukemia cells and its mechanism. METHODS: The
      expression of CD86 and CD80 was examined on the surfaces of NB4, HL-60, Kasumi-1,
      U937 and Jurkat cells by flow cytometric analysis after treated by SB or not.
      Allogeneic mixed lymphocyte reaction was used to evaluate the immunomodulatory
      effects of cells treated by SB. Activated NF-kappaB was measured with an NF
      kappaB assay kit. RESULTS: Up-regulation of CD86 and CD80 at various levels was
      observed on these leukemia cells treated by SB. The ratio of CD86 expressing cell
      in NB4 cells treated by 0.5 mmol/L SB was 36.8 times higher than that in control.
      Up-regulation of NF-kappaB was similar to that of CD86. Allogeneic lymphocyte
      proliferation was strongly stimulated by the SB treated cells. CONCLUSION: SB can
      improve the expression of CD86 in acute leukemia cells. NF-kappaB was an
      important transcription factor involved in the up-regulation of CD86.

PMID- 15949286
TI  - [The effect of tumor-dendritic cell fusion vaccines on the cytotoxicity of CIK/NK
      cells from cord blood].
AB  - OBJECTIVES: To evaluate the effects of K562-dendritic cell (DC) and Raji-DC
      fusion vaccines on the cytotoxicity of cord blood (CB) derived cytokine-induced
      killer/natural killer (CIK/NK) cells. METHODS: DC and CIK/NK cells were derived
      from CB mononuclear cells. CB-DC were fused with inactivated K562 or Raji cells
      by PEG to form K562 or Raji-DC fusion vaccine. The CIK/NK cells stimulated by
      different co-culture antigens were three groups: K562-DC or Raji-DC fusion
      vaccine group, inactivated K562 or Raji plus DC group, and CB-DC alone group. The
      cytotoxicity of CIK/NK cells stimulated by different co-culture antigens was
      measured by MTT test. RESULTS: All the antigens used for stimulation could
      enhance the cytotoxicity of CB-CIK/NK cells, with no specificity difference. At
      20:1 effector-target ratio, the cytolytic activities of K562-DC and Raji-DC
      fusion vaccine groups against Raji cells were (75.44 +/- 4.19)% and (81.33 +/-
      4.18)% respectively (P < 0.05); and that of inactivated K562 + DC and Raji + DC
      group against Raji cells were (73.12 +/- 4.22)% and (80.49 +/- 4.27)%,
      respectively (P < 0.01). There was no significant difference in the cytotoxicity
      to K562 cells between the two fusion vaccine groups (P > 0.05). The cytotoxicity
      of CB-CIK/NK cells immunized by Raji cells was higher than that by K562 cells. In
      CIK/NK cells co-stimulated by the same tumor antigen, there was no significant
      difference in the cytotoxicity between DC fusion vaccine group and inactivated
      cells plus DC group to different tumor cells. CONCLUSIONS: The cytotoxicity of CB
      CIK/NK cells to tumor cells was not specific. There was no significant difference
      in the cytotoxic activity of CB-CIK/NK cells between the DC fusion vaccine group
      and inactivated cells plus DC group.

PMID- 15949287
TI  - [Reduced intensity of BuCy conditioning regimen for transplantation in the
      treatment of malignant hematologic diseases].
AB  - OBJECTIVE: To evaluate the use of a new reduced intensity of BuCy conditioning
      regimen for the treatment of malignant hematologic diseases in aged or
      intolerable patients receiving allogeneic hematopoietic stem cell transplantation
      (allo-HSCT) from the siblings. METHODS: Twelve patients with acute lymphoblastic
      leukemia (ALL, n = 4), acute myelogenous leukemia (AML-M(2), n = 2), chronic
      myelogenous leukemia (CML, n = 4), and myelodysplastic syndromes-refractory
      anemia with excess blasts (MDS-RAEB, n = 2) were intolerant of conventional
      myeloablative therapy because of age (older than 50 years) or having severe
      concurrent diseases. The median age was 49 years (range 42-64 years). Seven were
      males and five females. Two of the 12 patients were HLA one antigen-mismatched
      and the rest HLA identical with their donors. The low dosage conditioning regimen
      consisted of busulfan (2 mg.kg(-1).d(-1) for 3 days), Ara-C (2 g.m(-2).d(-1) for
      1 or 2 times), cyclophosphamide (1.0 g.m(-2).d(-1) for 2 days) and anti-T
      lymphocyte globulin (ATG 2.5 mg.kg(-1).d(-1) for 4 days, -5 - -2 day).
      Granulocyte colony-stimulating factor mobilized bone marrow and peripheral blood
      stem cells (PBSC) were harvested (1 patient using PBSC alone). All patients
      received cyclosporin A, short-term MTX and mycophenolate mofetil (MMF) for
      prophylaxis of acute graft-versus-host disease (aGVHD). DNA short tandem repeat
      (STR) sequence analysis, cytogenetics and molecular-biologic technique were used
      to analyze chimerism. RESULTS: All the patients were well tolerated the regimen,
      with no severe regimen related toxicity. In all the 12 patients, absolute
      neutrophil count > or = 0.5 x10(9)/L was achieved in 11 to 17 (median 15) days
      and platelet count > 20 x 10(9)/L in 10 to 23 (median 15) days after
      transplantation. Complete chimerism was achieved in 11 patients and 1 patient was
      in mixed chimerism at one month after HSCT. With a median follow-up of 14.5 (4.0
      24.0) months, 7 of the 12 patients (58.0%) were alive and 5 (42.0%) of the 7 were
      disease-free. The probabilities of OS and DFS at 12 months were 75.0% and 48.1%.
      Five patients (41.6%) had aGVHD and four had local chronic GVHD with a cumulative
      probability of chronic GVHD of 41.5%. CONCLUSION: This reduced intensity
      conditioning regimen is well tolerated and safe for HSCT in the older patients or
      patients with severe concurrent medical conditions and can achieve full chimerism
      and long-term disease-free survival.

PMID- 15949289
TI  - [Severe gastrointestinal bleeding after allogeneic hematopoietic stem cell
      transplantation--15 case analysis].
AB  - OBJECTIVE: To analyze the features, causes, treatments and outcomes of severe
      gastrointestinal (GI) bleeding after allogeneic hematopoietic stem cell
      transplantation (allo-HSCT). METHODS: Fifteen patients suffered from massive GI
      bleeding (blood loss leading to hemorrhagic shock) or subacute GI bleeding (at
      least 1 or more units of red blood cell transfusion on each of two consecutive
      days) were observed and analyzed after allo-HSCT. RESULTS: Seventeen severe GI
      bleeding episodes occurred in 15 patients. The severe bleeding occurred in three
      periods of time: within 1 week, 1 to 2 months and 4 to 7 months after
      transplantation. The main manifestation was hematemesis and hematochezia in the
      first period, and hematochezia alone in the second and third periods. Platelet
      counts at the onset of severe bleeding were < or = 50 x 10(9)/L in the majority
      of patients. Causes of bleeding were conditioning regimen-related toxicity in 2
      patients/episodes, graft versus host disease (GVHD) or/and intestinal
      cytomegalovirus (CMV) or fungal infections in 11 patients/12 episodes, intestinal
      CMV infections in 1 patient/episode, acid-peptic ulcer in 2 patients/episodes,
      and cause unknown in 1 patient/episode. Supportive care such as transfusions of
      platelet, red blood cell and fresh frozen plasma, H2 receptor blockers and
      omeprazole were given to all patients, immunosuppressive drugs to patients
      developed GVHD and antiviral drugs to patients with complicated CMV infection.
      Eight patients/9 episodes of bleeding were controlled. Eight patients continued
      severe GI bleeding and died of acute GVHD or related serious complications.
      CONCLUSIONS: Severe GI bleeding after allo-HSCT are mainly caused by regimen
      related toxicity, GVHD or/and intestinal CMV infection. Bleeding caused by
      conditioning regimen-related toxicity is self-limited and has a better prognosis.
      However, treatment failure and mortality are high if the patient's bleeding
      resulted from GVHD and intestinal CMV infection.

PMID- 15949290
TI  - [Clinical features and prognostic factors in primary myelofibrosis patients under
      45 years old].
AB  - OBJECTIVE: To investigate the clinical and hematological features and identify
      the prognostic factors associated with short-term survival in primary
      myelofibrosis (PMF) patients under 45 years old. METHODS: The clinical
      manifestations, laboratory parameters, and survival were retrospectively analyzed
      in 56 PMF patients under 45 years old. Univariate analysis of prognostic factors
      was performed using Logrank test and multivariate analysis using COX model.
      RESULTS: Of the 56 patients, 27 were males and 29 females. The range of age was
      from 20 to 45 years (median 38 years). 84% of the patients were anemic and 66% Hb
      < 100 g/L. 32% of the patients had constitutional symptoms including fever, night
      sweats and weight loss. The median survival was 69 months (95% CI 11-127). By
      univariate analysis, Hb < 100 g/L, platelet count < 100 x 10(9)/L, WBC < 10 x
      10(9)/L, constitutional symptoms and the duration from first signs to diagnosis <
      or = 6 months were associated with poor prognosis. By multivariate analysis, only
      Hb < 100 g/L and constitutional symptoms were independently associated with short
      survival. With these two adverse prognostic factors, the patients could be
      separated into a high risk and a low risk groups, and the median survivals were
      16 and 88 months, respectively (P < 0.001). Using these two factors to predict
      the less than 3-years survival for individual patient, the sensitivity,
      specificity and positive predictive value were 67%, 100% and 100%, respectively.
      CONCLUSION: Hb < 100 g/L and constitutional symptoms in PMF patients under 45
      years old were significantly associated with short survival and poor prognosis.
      These two prognostic factors enabled to separate patients into a high and a low
      risk groups. The survival of high-risk patients was less than three years.

PMID- 15949291
TI  - [Induction of anti-B-cell acute lymphoblastic leukemia cytotoxic T lymphocyte
      response against immunoglobulin heavy chain frame-derived nonapeptide].
AB  - OBJECTIVE: To induce anti-B-cell acute lymphoblastic leukemia (B-ALL) cytotoxic T
      lymphocyte response against immunoglobulin heavy chain frame-derived nonapeptide.
      METHODS: The peptide, QLVQSGAEV, containing IgHV1 frame region 3rd-11th amino
      acids (IgHV1(3-11)), was synthesized. IgHV1(3-11)-T2 binding tests were
      performed. HLA-A * 0201-positive normal peripheral blood mononuclear cells
      (PBMNC) were stimulated by IgHV1(3-11)-loaded antigen presenting cells three
      times at weekly intervals. HLA-A * 0201/IgHV1(3-11) tetramers were used to detect
      the proliferation of IgHV1(3-11)-specific CD8(+) T cells in the culture. Seven
      IgHV gene families of B-ALL patients were respectively amplified by PCR and the
      PCR products were sequenced to select IgHV1 and IgHV3 family monoallelic
      functional rearrangements. Among them, HLA-A * 0201 positive individuals were
      subsequently identified. Cytotoxicity of IgHV1(3-11)-specific CD8(+) T cells
      against HLA-A * 0201-positive IgHV1/IgHV3 family B-ALL cells was measured by MTT
      assay. RESULTS: The synthesized IgHV1(3-11) up-regulated HLA-A * 0201 expression
      on T2 cell surface by 1.63-folds. The percentage of IgHV1(3-11)-specific CD8(+) T
      cells in HLA-A * 0201-positive normal PBMNC was increased from 1.64% after second
      stimulation to 82.57% after third stimulation. At effector: target ratio of 20:1,
      the killing rate of IgHV1(3-11)-specific CD8(+) T cells against IgHV1 family B
      ALL cells was 18.24%, being 1.8-folds as that against IgHV3 family B-ALL cells (P
      = 0.01). CONCLUSION: Cytolytic T lymphocytes generated in vitro against
      immunoglobulin heavy chain frame-derived nonapeptides can kill B-ALL cells
      expressing these peptides.

PMID- 15949292
TI  - [Study on the up-regulation of B7 molecules expression and immunogenicity of
      acute leukemia cells induced by interleukin 7].
AB  - OBJECTIVE: To investigate the effects of interleukin 7 (IL-7) on B7 molecules
      expression and immunogenicity of acute leukemia (AL) cells. METHODS: The B7
      molecules expression on fresh acute leukemia cells and on the IL-7 exposed
      leukemia cells was detected by FACScan cytometer. B7-1 and B7-2 mRNA in IL-7
      treated HL-60 cells were detected by reverse transcription-PCR (RT-PCR). The
      stimulation of proliferation of allogeneic peripheral blood mononuclear cells
      (PBMNC) by IL-7 treated leukemia cells was detected by MTT method. The level of
      interferon-gamma (IFN-gamma) secreted by the stimulated PBMNC was determined
      using enzyme-linked immunosorbent assays (ELISA). The blocking experiments were
      performed using monoclonal antibodies against B7-1, B7-2 and W6/32. RESULTS: B7-1
      was weakly expressed in three, whereas B7-2 did in only one of eleven AL
      patients. IL-7 significantly enhanced B7 molecules expression on AL cells in a
      time-dependent manner. Furthermore, IL-7 could induce higher expression of B7-1
      and B7-2 mRNAs on HL-60 cells. IL-7 treated leukemia cells could stimulate PBMNC
      proliferation and promote their IFN-gamma production. Anti-B7-1 and anti W6/32
      but not anti-B7-2 monoclonal antibodies significantly inhibited the stimulated
      PBMNC proliferation and IFN-gamma secretion. CONCLUSION: Fresh AL cells express
      low level of B7-1 and B7-2 molecules. IL-7 enhances the B7 molecules expression
      on AL cells. The IL-7-treated leukemia cells can significantly stimulate the
      proliferation of allogeneic PBMNC and induce their IFN gamma secretion.

PMID- 15949293
TI  - [Effects of MAPK antagonist on TPO stimulated UT2 cells proliferation and
      differentiation].
AB  - OBJECTIVE: To explore the effects of MAPK antagonist on TPO stimulated UT7 cell
      proliferation and differentiation, and to elucidate the mechanism of TPO
      functioning on UT7 cells. METHODS: EGFP pMSCV and MEK 1 pMSCV MEK 1 plasmids were
      transferred into UT7 cells. Phosphorylated MEK1 of UT7 cells was examined by
      Western blot. The proliferation and CD41 expression of UT7 cells transfected with
      mutant (ser222A) MEK1 or exposed to PD98059 were examined. RESULTS: (1) 60.73%
      EGFP positive cells were obtained in retroviral vector MEK1 pMSCV transfected
      UT7cells. (2) In different time of TPO stimulating UT7 cells, the level of
      phosphorylated MEK1 was lower in experiment group than in control group. In
      experiment group, the level of phosphorylated MEK1 was decreased after stimulated
      by TPO for 1 hour, and almost disappeared after stimulated for 3 hours. (3) The
      effect of TPO on UT7 cell proliferation was inhibited by PD98059 and the
      transfected mutation MEK1 gene. The proliferation rate was 98.58% in DMSO control
      group, 39.00% in PD98059 group (P < 0.05), 102.13% in EGFP pMSCV group, and
      48.94% in MEK1pMSCV (P < 0.05). (4) The CD41 expression on UT7 was inhibited by
      PD98059 and the transfected mutation MEK1 gene. CONCLUSION: Phosphorylation of
      MEK1 in UT7 cells can be induced by TPO. There was a relationship between the TPO
      stimulating time and phosphorylation of MEK1. The effects of TPO on UT7 cell
      proliferation and CD41 expression is mediated by MAPK signal transduction
      pathway.

PMID- 15949294
TI  - [MEKK2 regulates the production of interleukin 2].
AB  - OBJECTIVE: To study the role of MEKK2 on the production of IL-2 in Jurkat cells
      stimulated by PHA/anti-CD28 antibody. METHODS: The MEKK2 and JNK kinase
      activities were measured in both dominant negative MEKK2 Jurkat (dnMEKK2 Jurkat)
      cells and parental Jurkat cells. The AP(1) and IL-2 promotor activities were
      measured by luciferase activity assay. The IL-2 mRNA and protein were detected by
      RT-PCR and Western blot. RESULTS: After stimulation by PHA/anti-CD28, JNK was
      activated in parental Jurkat cells but not in dnMEKK2 Jurkat cells. The
      luciferase report gene activities of AP1 and IL-2 promotors were increased by 4-
      and 5-folds in parental cells whereas only by 1 fold in dnMEKK2 Jurkat cells. The
      level of IL-2 mRNA and IL-2 protein were increased in parental Jurkat cells but
      not in dnMEKK2 Jurkat cells. CONCLUSION: MEKK2 plays an important role on the
      production of IL-2 in Jurkat cell stimulated with PHA/anti-CD28 antibody. It is a
      potential drug target for the treatment of GVHD and autoimmune disease.

PMID- 15949295
TI  - [Detection of CCAAT/enhancer binding protein alpha gene mutations in acute
      myeloid leukemia].
AB  - OBJECTIVE: To explore the relationship between CCAAT/enhancer binding protein
      alpha (C/EBPalpha) gene mutations and the development of acute myeloid leukemia
      (AML). METHODS: The whole coding region of C/EBPalpha gene were screened in 48
      cases of AML and 11 normal subjects by PCR-single strand conformation
      polymorphism (PCR-SSCP) and sequencing. RESULTS: C/EBPalpha mutations were
      detected in 5 of 48 AML patients. Four duplications and 1 deletion were confirmed
      by DNA sequencing. All of those are newly identified mutations. CONCLUSIONS:
      Different mutation types of C/EBPalpha gene exist in a small number of patients
      with AML and might be related to the pathogenesis of some leukemias.

PMID- 15949305
TI  - [Advances in molecular biology of tuberculosis].

PMID- 15949306
TI  - [Evaluation of the mycobacterial interspersed repetitive units typing as a
      practical approach in molecular epidemiology of Mycobacterium tuberculosis].
AB  - OBJECTIVE: To introduce a new genotyping method, mycobacterial interspersed
      repetitive units (MIRU) typing, for Mycobacterium tuberculosis and to evaluate
      its feasibility. METHODS: Mycobacterium tuberculosis strains stored at Shanghai
      Municipal Center for Disease Control and Prevention during 2000 to 2002, were
      randomly selected by simple digital table and genotyped by MIRU and
      Spoligotyping. RESULTS: By Spoligotyping method, 91 strains were typed to 20
      genotypes, of which 89% (81/91) strains belonged to Beijing genotype, while by
      MIRU method, these strains were divided into 46 genotypes. The MIRU typing showed
      high discriminatory power, especially for the Beijing genotype strains. The 81
      Beijing genotype strains could be subdivided into 39 different MIRU genotypes. In
      this sample collection, 12 MIRU loci showed different discriminative according to
      their allelic diversity. Locus 26 showed highly discriminative, while locus 16,
      31, and 40 showed moderately discriminative. CONCLUSIONS: MIRU genotyping is a
      simple and fast method. Its numerical result facilitates the comparison among
      strains of Mycobacterium tuberculosis from different labs.

PMID- 15949307
TI  - [Rapid detection of rifampin resistance of Mycobacterium tuberculosis using high
      throughput pyrosequencing technique].
AB  - OBJECTIVE: To develop a pyrosequencing approach to rapid detection of rifampin
      resistance in Mycobacterium tuberculosis based on characterization of all
      possible mutations in the 81 bp core region. METHODS: Two pyrosequencing
      sequencing primers and 1 pair of PCR primers were chosen for pyrosequencing
      analysis. The sensitivity of the pyrosequencing approach was determined by
      assaying PCR products generated from 10-fold serial dilutions of the DNA from
      Mycobacterium tuberculosis H(37) Rv strains. The efficacy of the pyrosequencing
      approach was evaluated by analyzing clinical Mycobacterium tuberculosis isolates
      with known antibiotic phenotypes. RESULTS: Rifampin resistance could be
      determined within 2 hours after PCR amplification and single-stranded template
      preparation by using only two pyrosequencing reactions. About 50 fg DNA/reaction
      was required in order to get sufficient PCR product for producing a long, clear
      and accurate pyrosequencing pattern. A total of 41 Mycobacterium tuberculosis
      isolates were tested and the results were concordant with those based on drug
      susceptibility testing and conventional DNA sequencing. CONCLUSION: The
      pyrosequencing technique is simple to perform and can be used as a rapid, high
      throughput and efficient method for detecting rifampin resistance in
      Mycobacterium tuberculosis.

PMID- 15949308
TI  - [Study of the expression profile of immunogenesis associated genes in
      tuberculosis by microarray].
AB  - OBJECTIVE: To explore the difference of gene expression profile in tuberculosis
      patients. METHODS: mRNA levels of pleural fluid and peripheral blood mononuclear
      cells (PBMC) in tuberculous pleurisy and lung cancer patients were compared by
      cDNA microarray. Paired mRNAs from fluid specimens of tuberculosis and lung
      cancer cases were labeled with different fluorochromes during cDNA probe
      synthesis in a reverse-transcription reaction. The signal intensity of each spot
      was measured by laser scanner and gene expression was quantified as the tubercle
      to-normal fluorescence ratio (T:N ratio). The gene was defined as over expression
      when the T:N ratio was greater than 2.0 and under expression when the ratio was
      less than 0.5. RESULTS: Among 626 immunogenesis associated genes there were 53
      differences, of which 31 (tnf-alpha, ig-lambda, il-17, il-17r, hla-dp, lcp1,
      tcralpha, tcrbeta, hsp75, cxcr4, fyb, hla-g, hla-a, il18bp, il-2r, lt-beta, il-8,
      ip-10, mcp-1, il-12, il-12r, il-10, canx, irf2, ifn-gamma, tlr, il-1, il-7, tlr,
      lsp-1, il-14)were higher and 22 (il-4, il-18, il-15, ifg-1, scya14, ablim, peci,
      ppid, hsf 2, actg2, maoa, ttid, gatm, tgfb3, insr, thbd, trap1, tcrgamma,
      tcrdelta, il-13r, il-11, igf1, a2m)were lower in tuberculous pleurisy than those
      in the control. CONCLUSIONS: The immunogenesis of tuberculosis involves multi
      genetic expression changes, such as tnf-alpha, il-17, il-12, tcralpha, tcrbeta,
      hsp75, cxcr4, il-4, il-18, il-15 etc., the expression profile of which changed
      dramatically. The results provide new insight for understanding of the pathogenic
      mechanisms of tuberculosis and exploring new therapeutic strategies.

PMID- 15949309
TI  - [Therapeutic effects of DNA vaccines in a murine model of Mycobacterium
      tuberculosis infection].
AB  - OBJECTIVE: To study the effects and mechanisms of DNA vaccines encoding
      Mycobacterium tuberculosis antigens on murine Mycobacterium tuberculosis
      infection. METHODS: C57BL/J6 mice infected with Mycobacterium tuberculosis were
      treated with normal saline (NS), pCDNA3.1, psIL-12, pcD85B, pcDMPT64, pcD85B +
      pcDMPT64, and pcD85B + psIL-12 respectively. The numbers of viable bacteria in
      the lung and the spleen were counted. The levels of IFN-gamma, IL-4 and TNF-alpha
      of spleen lymphocytes stimulated with PPD were detected with ELISA. Lungs and
      spleens were prepared for pathological analysis. RESULTS: The pcD85B group (6.99
      +/- 0.40 in lung, 5.17 +/- 0.33 in spleen), the psIL-12 group (7.41 +/- 0.50 in
      lung, 5.31 +/- 0.21 in spleen)and the pcD85B + psIL-12 group (7.64 +/- 0.28 in
      lung, 5.49 +/- 0.31 in spleen) showed significantly reduced number of colony
      forming units (lg(-1) CFU/g, x +/- s) in lungs and spleens compared with the
      control mice (5.76 +/- 0.16 in saline, 5.88 +/- 0.21 in pCDNA3.1), but the
      difference between the pcD85B group and the pcD85B + psIL-12 group was not
      significant. pcD85B vaccination induced high levels of IFN-gamma and TNF-alpha.
      No change of IL-4 was found in all groups. The pathological changes in lungs of
      the pcD85B group were localized, while those in the control group were extensive.
      There was no significant changes in the spleen of all groups. CONCLUSIONS: Ag85B
      DNA vaccination had immunotherapeutic effects, which were associated with a
      switch to Th1 response and enhanced production of cytokines TNF-alpha and INF
      gamma. psIL-12 alone showed therapeutic effect, but it didn't enhance the
      therapeutic effect of single Ag85B DNA vaccination.

PMID- 15949310
TI  - [Study on the molecular epidemiology of Stenotrophomonas maltophilia infection in
      patients on mechanical ventilation].
AB  - OBJECTIVE: To investigate a potential outbreak of Stenotrophomonas maltophilia
      (pma) infection occurred in patients on mechanical ventilation in a respiratory
      ICU (RICU) and to track the infective origins by antibiotype and pulsed-field gel
      electrophoresis (PFGE) typing methods. METHODS: (1) Thirteen pma strains were
      isolated from 9 patients on mechanical ventilation (9 strains), hand swabs of
      medical staffs in RICU (2 strains) and fiberscope used for intubations and
      aspiration (2 strains) from December, 2002 to February, 2003. (2) Sixteen strains
      gathered from different wards during the period of 1997 - 2000 were collected and
      used as control. (3) Antibiotic susceptibility data of all strains were
      collected. (4) Homology of the strains was analyzed by the methods of antibiotype
      and PFGE genotype. RESULTS: Of the 9 pma isolated from patients on mechanical
      ventilation, eight had identical PFGE genotype. The isolates from two RICU staffs
      and two fiberscope displayed the same genotype with the eight patients above.
      Seven of the 9 isolates shared an identical antibiotype. The consistent rate of
      antibiotype with PFGE genotype was 85% (11/13). There were 11 PFGE genotypes and
      9 antibiotypes in 16 strains of the control group, which indicated that they came
      from different clones. CONCLUSIONS: Eight pma strains of patients in RICU came
      from the same clone. This result proved that clone transmission occurred in
      patients on mechanical ventilation. Contaminated fiberscope and hands of staffs
      may be the infective origin and the route of transmission.

PMID- 15949311
TI  - [The molecular mechanisms of the effects of murine interferon-gamma transgenic
      expression on allergen-induced allergic model via adenoviral vector].
AB  - OBJECTIVE: To investigate adenoviral vector mediated murine interferon-gamma
      (mIFN-gamma) transgene expression and its effect on allergen-induced airway
      inflammation and multiple interleukin (IL) cytokines (IL-4, IL-5, IL-6, IL-10, IL
      12, IL-13 and IL-18) expression in a murine allergic model. METHODS: Forty-eight
      mice were divided into 7 groups by random digits table: a negative control group
      (A), allergic model groups I, II, III (B, D, F), gene therapy groups I, II, III
      (C, E, G). Except for group A, mice of the other groups were peritoneally
      sensitized with ovalbumin (OVA, 15 microg/mouse) twice on day 0 and day 5, and
      challenged by inhalation of 0.5% OVA (20 ml per time) twice per day from day 12
      to 14. On day 15, AdCMVmIFN-gamma (5 x 10(9) PFU/mouse) solution 50 microl was
      administrated by nasal drip in groups C, E and G. For groups A, B, D and F, 0.9%
      NaCl 50 microl was administrated by nasal drip. Groups A, B and C were sacrificed
      on day 18. Groups D and E were sacrificed on day 21. Groups F and G were
      sacrificed on day 25. The concentration of mIFN-gamma in bronchioalveolar lavage
      (BALF) was measured by enzyme-linked immunosorbant assay. Accumulation of
      inflammatory cells and eosinophils (EOS) were quantified by cell count and
      histopathological analysis. Multi-cytokine expression was tested by semi
      quantitative reverse transcription polymerase chain reaction (RT-PCR). RESULTS:
      (1) mIFN-gamma was efficiently expressed after gene therapy. The concentration of
      mIFN-gamma in BALF was (729.0 +/- 104.7) pg/ml 3 days after gene therapy (group
      C); it was (984.5 +/- 119.1) pg/ml after 6 days (group E); and (310.6 +/- 59.7)
      pg/ml after 10 days (group G). (2) The total cell number in BALF of group B and C
      was (318 +/- 41) x 10(3)/ml and (137 +/- 12) x 10(3)/ml, respectively (P < 0.01);
      the constituent ratio of EOS in BALF was 0.715 +/- 0.054 and 0.452 +/- 0.016,
      respectively (P < 0.01). The total cell number in BALF of group D and E was (183
      +/- 23) x 10(3)/ml and (92 +/- 6) x 10(3)/ml, respectively (P < 0.01); the
      constituent ratio of EOS was 0.393 +/- 0.065 and 0.083 +/- 0.038, respectively (P
      < 0.01). The total cell number in BALF of groups F and G was (196 +/- 7) x
      10(3)/ml and (98 +/- 15) x 10(3)/ml, respectively (P < 0.01); the constituent
      ratio of EOS was 0.253 +/- 0.035 and 0.068 +/- 0.025, respectively (P < 0.01).
      (3) The histopathological results showed that in the gene therapy groups, the
      infiltration of inflammatory cells was markedly reduced and the damage of airway
      epithelium was alleviated. (4) For group D and E, the ratio of IL-10 mRNA
      abundance to that of home gene was 0.14 +/- 0.10 and 0.49 +/- 0.27, respectively
      (P < 0.01); that of IL-12 was 0.15 +/- 0.05 and 0.63 +/- 0.17, respectively (P <
      0.01); that of IL-13 was 0.76 +/- 0.17 and 0.37 +/- 0.10, respectively (P <
      0.01). For group F and G, the ratio of IL-10 mRNA abundance to that of home gene
      was 0.13 +/- 0.04 and 0.27 +/- 0.17, respectively (P = 0.019); that of IL-12 was
      0.14 +/- 0.05 and 0.35 +/- 0.21, respectively (P = 0.006); that of IL-13 was 0.57
      +/- 0.24 and 0.30 +/- 0.09, respectively (P = 0.003). However, there were no
      statistically significant changes in IL-4, IL-5, IL-6, and IL-18 in lung tissue
      between allergic model groups (B, D, F) and gene therapy groups (C, E, G, P >
      0.05). CONCLUSIONS: (1) mIFN-gamma gene transferred via adenoviral vector could
      abrogate the infiltration of EOS in OVA-induced allergic model. (2) The molecular
      mechanisms for effect by AdCMVmIFN-gamma transgenic therapy on murine allergic
      model involve the indirect action by the upregulation of IL-10 and IL-12
      expression and the downregulation of IL-13 expression locally in the lungs, in
      addition to the direct effects of locally overexpressed mIFN-gamma.

PMID- 15949312
TI  - [Simvastatin induces eosinophil apoptosis in vitro].
AB  - OBJECTIVE: To investigate the effect of simvastatin, a 3-hydroxy-3-methylglutaryl
      CoA reductase (HMGR) inhibitor, on eosinophils (EOSs) apoptosis in asthma
      patients. METHODS: Peripheral blood EOSs from 10 asthma patients were cultured in
      the presence or absence of simvastatin (1, 5, 10, 20 micromol/L), together with
      or without mevalonate (100 micromol/L) for 6, 12, 24, and 48 h. Apoptosis was
      monitored by annexin V/PI staining and flow cytometry. Caspase-3 was measured by
      enzyme-linked immunosorbent assay (ELISA). RESULTS: EOSs were particularly
      susceptible to apoptosis after incubated with 5 micromol/L simvastatin for 6, 12,
      24, and 48 h [the rates of EOSs undergoing apoptosis were: (23 +/- 3)%, (24 +/-
      3)%, (41 +/- 6)%, (70 +/- 12)% in control and (32 +/- 4)%, (47 +/- 7)%, (62 +/-
      9)%, (86 +/- 14)% in simvastatin; compared with control at the same time point: P
      = 0.000]. EOS apoptosis occurred at doses of 1 micromol/L and was already maximal
      at 5 micromol/L after incubated with simvastatin for 12 h [the rates of EOSs
      undergoing apoptosis were: (24 +/- 3)% in control, (37 +/- 3)%, (51 +/- 3)%, (53
      +/- 4)%, (52 +/- 4)% in 1, 5, 10, 20 micromol/L simvastatin, respectively;
      compared with control: P = 0.000]. The level of caspase-3 in EOSs was consistent
      with the rate of cell apoptosis [(8 +/- 3) microg/L in control, (14 +/- 4), (22
      +/- 4), (24 +/- 4), (23 +/- 5) microg/L in 1, 5, 10, 20 micromol/L simvastatin,
      respectively; compared with control: P = 0.000 - 0.003]. However, Co-incubation
      of simvastatin with mevalonate (the production of HMGR) completely reversed the
      activity of simvastatin on EOS apoptosis even when the highest simvastatin (20
      micromol/L) dose was used; the rates of EOSs undergoing apoptosis in the control,
      mevalonate plus simvastatin and simvastatin alone were (24 +/- 3)%, (52 +/- 4)%
      and (25 +/- 3)%, respectively; while the caspase-3 levels were (8 +/- 3)
      microg/L, (23 +/- 5) microg/L and (9 +/- 3) microg/L, respectively. CONCLUSION:
      Simvastatin induces apoptosis of EOSs in asthma patients via its ability to block
      the synthesis of the important isoprenoid intermediates, which leads to the
      inhibition of small GTP-binding protein activity.

PMID- 15949313
TI  - [Expressions of cyclooxygenase-2 and matrix metalloproteinase-2 and airflow
      obstruction in patients with chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To investigate the expression of cyclooxygenase-2 (COX-2) and matrix
      metalloproteinase-2 (MMP-2) in induced sputum and airway obstruction in patients
      with stable chronic obstructive pulmonary disease (COPD). METHODS: Fifty-five
      patients with stable COPD and 10 age-matched controls were enrolled in the study.
      Sputum induction was collected by inhalation of 3% sodium chloride. Cell numbers
      and differentials in sputum suspension were counted with Wright's stain. The
      concentrations of prostaglandin E(2) (PGE(2)) and MMP-2 in sputum supernatant
      were measured by ELISA. COX-2 protein expression in the cells was detected by
      Western blot. RESULTS: The total sputum cells, the numbers of alveolar
      macrophages (AM) and neutrophils (Neu) in COPD patients were significantly higher
      than those in the control group (P < 0.05 or P < 0.01). The number of AM and Neu
      was inversely correlated with FEV(1)%pred and FEV(1)/FVC (r = -0.280, P < 0.05, r
      = -0.345, P < 0.01; r = -0.677, r = -0.773, all P < 0.01). The level of COX-2
      protein expression was higher in induced sputum in COPD patients than that in the
      control group. Concentrations of PGE(2) in the control group and in COPD patients
      with grade 0, I, IIA, IIB and III were (81 +/- 18), (111 +/- 17), (117 +/- 23),
      (118 +/- 29), (153 +/- 24), (194 +/- 28) ng/L, respectively. Concentrations of
      MMP-2 in the control group and in COPD patients with grade 0, I, IIA, IIB and III
      were (0.7 +/- 0.4), (4.0 +/- 0.9), (4.5 +/- 1.5), (7.7 +/- 3.1), (11.9 +/- 3.5),
      (18.5 +/- 5.0)microg/L, respectively. Concentrations of PGE(2) and MMP-2 in
      sputum in COPD patients were significantly higher than those in the control group
      (all P < 0.01). PGE(2) and MMP-2 were inversely correlated with FEV(1)%pred,
      FEV(1)/FVC in stable COPD patients (r = -0.748, r = -0.750, P < 0.01; r = -0.801,
      r = -0.816, all P < 0.01). Concentrations of PGE(2) were positively correlated
      with MMP-2 in COPD patients (r = 0.775, P < 0.01). CONCLUSIONS: (1) There is
      chronic inflammatory process in airway of stable COPD. AM and Neu contribute to
      the process. (2) COX-2 and MMP-2 may be involved in the airway inflammatory
      process and contribute to airway remodeling in COPD.

PMID- 15949314
TI  - [Mitogen-activated protein kinase regulated hypoxia-inducible factor 1alpha in
      hypoxia-induced pulmonary hypertension in rats].
AB  - OBJECTIVE: To investigate the dynamic expression of hypoxia-inducible factor
      1alpha (HIF-1alpha) and mitogen-activated protein kinase (MAPK) in pulmonary
      arteries of rats with hypoxia-induced pulmonary hypertension. METHODS: Forty male
      adult Wistar rats were randomly divided into five groups:a control group (C
      group) and groups with hypoxia for 3, 7, 14 and 21 days (H(3), H(7), H(14) and
      H(21) group), eight rats per group. Mean pulmonary pressure (mPAP), right
      ventrical hypertrophy index (RVHI) and vessel morphometry were measured. The
      levels of HIF-1alpha mRNA expression in lung tissue was measured by in site
      hybridization (ISH). The protein expression of HIF-1alpha and p-ERK, p-JNK, p-P38
      were observed by immunohistochemistry or Western blot. RESULTS: The level of mPAP
      [(23.5 +/- 1.8) mm Hg], the ratio of vascular wall thickness to external diameter
      [WT, (45.5 +/- 3.1)%] and the ratio of vascular wall area to the total area [LA,
      (54.7 +/- 3.2)%] were significantly higher in H(7) group than those in C group
      [(16.2 +/- 2.0) mm Hg, (36.8 +/- 2.5)% and (63.2 +/- 2.5)% respectively, all P <
      0.05]. These parameters reached a high level and remained stable on H(14) group,
      RVHI was significantly higher [(26.9 +/- 1.3)%] on H(14) group than in C group
      [(23.0 +/- 1.5)%, P < 0.05]. Expression of p-ERK protein in C group was barely
      positive, but was up-regulated in pulmonary arterial tunica intima and tunica
      media of all hypoxia rats. Expression of p-JNK and p-P38 in C group and hypoxia
      groups were barely positive. Expression of HIF-1alpha protein in C group was
      barely positive, but was up-regulated in pulmonary arterial tunica intima of all
      hypoxic rats. In pulmonary arterial tunica media, the levels of HIF-1alpha
      protein was markedly up-regulated in H(3) group (0.209 +/- 0.009, P < 0.05),
      reaching its peak at H(7) group (0.232 +/- 0.008, P < 0.05), then tended to
      decline in H(14) group and H(21) group. HIF-1alpha mRNA staining was barely
      positive in C group, H(3) group and H(7) group, but began to increase
      significantly at H(14) group (0.305 +/- 0.104, P < 0.05), then remained stable in
      pulmonary arterial tunica intima. Linear correlation analysis showed that p-ERK,
      HIF-1alpha mRNA and mPAP were correlated with vessel morphometry and RVHI (P <
      0.01); p-ERK was positively correlated with HIF-1alpha mRNA and protein (tunica
      intima). CONCLUSION: MAPK as a signal transduction may play an important role in
      the development of hypoxia-induced pulmonary hypertension.

PMID- 15949315
TI  - [Ectogenous fragile histidine triad gene inhibits the malignant phenotype of
      human lung cancer cell line A549 in vitro and in vivo].
AB  - OBJECTIVE: To investigate the inhibition effects of fragile histidine triad
      (FHIT) gene on the malignant growth of A549 cell line. METHODS: A mammalian
      expression vector PEGFP-FHIT was constructed and transfected into the A549 cell
      line by lipofectamine. Then the transfected cell line was screened by G418.
      Individual G418-resistant colonies were isolated by limited dilution. The
      monoclonal transfected cell line was screened by RT-PCR and immunochemical
      staining. The inhibition growth efficacy of extraneous FHIT was evaluated by
      clonogenic survival assay, flow cytometry and heteroplastic transplant on nude
      mice. RESULTS: Presence of extraneous FHIT gene in FHIT-A549 cell was proved by
      RT-PCR. Immunochemical stain demonstrated that the expression of extraneous FHIT
      protein was positive in FHIT-A549 cell and negative in PEGFP-A549 cell and A549
      cell. The clonal formation rate of FHIT-A549 (2.6%) was significantly lower than
      that of A549 cell (50.1%) and PEGFP-A549 cell (53.6%, P < 0.01). FHIT-A549 cell
      (95.8%) was blocked in G(2) phage. Tumorigenicity of A549 cells in nude mice was
      greatly inhibited by expression of ectogenous FHIT gene. The weight of tumor was
      significantly lower in FHIT-A549 cell (0.04 +/- 0.03) than in A549 cell (0.24 +/-
      0.11) and PEGFP-A549 cell (0.25 +/- 0.07, P < 0.01). CONCLUSIONS: Reintroduction
      of the expression of ectogeneous FHIT gene can obviously suppress the
      proliferation and tumorigenicity in human lung cancer cell line A549 and induce
      apoptosis. The data demonstrate oncosuppressive properties of FHIT gene.

PMID- 15949317
TI  - [Application of gene typing approach based on variable-number tandem repeats
      mycobacterial interspersed repetitive units in the epidemiological study of
      Mycobacterium tuberculosis].

PMID- 15949316
TI  - [Antitumor effect of epidermal growth factor receptor gene silencing].
AB  - OBJECTIVE: To investigate whether chemically synthesized double-stranded RNA
      (dsRNA) targeting epidermal growth factor receptor (EGFR) could induce gene
      silencing in non-small-cell lung cancer (NSCLC) cells, and to assess the degree
      of EGFR gene silencing and its effect on functional outcome. METHODS: NSCLC cell
      line SPC-A-1 was transfected with target sequence-specific dsRNA formulated with
      Lipofectamine 2000. Fluorescent microscopy and flow cytometry were used to
      measure the reduction in the production of the EGFR protein. Real-time PCR was
      used to detect the silencing of the EGFR gene level. Colony assay was adopted to
      measure the cellular proliferation and colony formation. A tumor burdened athymic
      nude mouse model was established to calculate the tumor growth inhibition rate.
      RESULTS: The dsRNA-EGFR was shown to be effective with a 71.3% down-regulation of
      EGFR protein production and 50.0% of silencing of EGFR gene. The dsRNA-EGFR
      significantly reduced colony numbers by 66.8% in vitro and inhibited the tumor
      growth in vivo. The tumor growth inhibition rate was 75.0%. CONCLUSION: The
      sequence specific dsRNA showed a blockbuster effect in downregulation of EGFR
      gene level and protein production, inhibition of the cellular proliferation and
      tumor growth.

PMID- 15949325
TI  - [Reconsideration of cancer as a systems disease concept].

PMID- 15949318
TI  - [Progress in the diagnosis and management of acute exacerbations of chronic
      obstructive pulmonary disease].

PMID- 15949326
TI  - [Development to improve the level of city community health services].

PMID- 15949327
TI  - [Clinico-pathological characteristics of surgical effect on periampullary
      cancers: report of 631 cases].
AB  - OBJECTIVE: To analyze the differences and relationships among periampullary
      cancers. METHODS: A retrospective study was accomplished on the clinical
      manifestation, pathological behavior and postoperative survival of 631 patients
      with periampullary cancer hospitalized from Jan 1980 to Dec 2003. RESULTS: The
      characteristics of different periampullary cancers, in the order of carcinoma of
      head of pancreas (n = 352), carcinoma of common bile duct (n = 42), carcinoma of
      Vater's ampulla (n = 189), and duodenal cancer (n = 48) were as follows: (1) the
      mean duration of symptoms were 11.9 +/- 1.3, 5.8 +/- 0.9, 6.3 +/- 0.6, and 18.3
      +/- 4.0 weeks (F = 6.18, P < 0.01); (2) the serum total bilirubin was 225 +/- 10,
      345 +/- 35, 235 +/- 13, and 50 +/- 13 micromol/L(chi(2) = 68.49, P < 0.01); (3)
      the mean tumor size was 6.0 +/- 2.2, 3.0 +/- 1.3, 3.0 +/- 1.9, and 4.8 +/- 3.9 cm
      respectively (chi(2) = 255.7, P < 0.01); (4) adenocarcinoma accounted for 88%.
      Distant metastasis occurred in 98 cases, mostly to liver, abdominal cavity, and
      omentum. Local invasion mainly occurred in duodenum (chi(2) = 10.76, P < 0.01),
      common bile duct (chi(2) = 15.16, P < 0.01), and periampullary tissues (chi(2) =
      22.49, P < 0.01), and great vessels (chi(2) = 51.25, P < 0.01). (5) the T staging
      (chi(2) = 11.68, P < 0.01) and lymph node status (chi(2) = 8.33, P < 0.05) of the
      removed tumor specimens were different among different kinds of carcinomas; (6)
      local invasion of duodenum (chi(2) = 10.76, P < 0.01), common bile duct (chi(2) =
      15.16, P < 0.001), periampullary tissues (chi(2) = 22.49, P < 0.01), and great
      vessel (chi(2) = 51.25, P < 0.01) occurred in unresectable carcinomas; (7) the
      resection rates were 13% (n = 46), 50% (n = 21), 74% (n = 139), and 56% (n = 27)
      respectively (chi(2) = 205.6, P < 0.01); (8) the postoperative median survival
      periods were 6.0 +/- 0.3, 13.0 +/- 1.2, 22.0 +/- 1.6, and 13.0 +/- 2.5 months
      respectively (chi(2) = 173.47, P < 0.01). CONCLUSION: Different tumor has its
      predominant clinical manifestation, pathological character, the probability of
      resection, and postoperative median survival. The prognosis after surgical
      treatment may be decided by biological behavior of tumor itself.

PMID- 15949328
TI  - [Expression of ER, PR and cyclin D1 in breast infiltrating ductal carcinoma and
      their clinicopathological significance].
AB  - OBJECTIVE: To investigate the expression of cyclin D1, ER, and PR gene proteins
      and to analyze their relevance to tumor biological characteristics, chemotherapy
      effects, diseases free survival (DFS) and overall survival (OS) of patients.
      METHODS: Immunohistochemical staining techniques was used to detect the
      expression of cyclin D1, ER and PR gene protein in 100 samples of breast
      infiltrating ductal carcinoma patients, all female, aged 49.49 +/- 10.81 (28
      approximately 92). RESULTS: The positive expression rate of gene protein was 60&
      for ER 58% for PR, and 55% for cyclin D1 ER, PR presented a negative correlation
      to SBR grading. Patients with cyclin D1 positive tumor had longer OS than those
      with cyclin D1 negative tumor (P = 0.0053). Coexpression of cyclin D1 and ER was
      significantly correlated with longer DFS and OS (P(dfs) = 0.0108, P(os) =
      0.0030). The positivity of ER and PR was significantly correlated with longer DFS
      (P(ER) = 0.0322, P(PR) = 0.0129). For those patients receiving postoperative
      adjuvant chemotherapy, the expression of ER and PR were correlated with a better
      prognosis and longer DFS. The patients with cyclin D1 negative tumor, who
      received CAF, had a mean DFS of 51.6 months and a mean OS of 57 months in
      comparison with 24.8 months and 31.2 months for those patients who received other
      chemotherapy. CONCLUSION: In breast infiltrating ductal carcinoma patients
      expression of ER and of PR are correlated with longer DFS, cyclin D1 expression
      is correlated with longer OS. For the patients receiving postoperative adjuvant
      chemotherapy, the expression of ER and PR correlated to a better prognosis and
      longer DFS. The patients with cyclin D1 negative tumor who receive CAF
      chemotherapy have longer DFS and OS than those receiving other chemotherapy.

PMID- 15949329
TI  - [Construction of glucosylceramide synthase-specific siRNA expression vector and
      its efficiency in reversal of drug resistance in breast carcinoma cells].
AB  - OBJECTIVE: To construct a glucosylceramide synthase (GCS)-specific small
      interfering RNA (siRNA) expression vector and to investigate the inhibitory
      effect of this siRNA on GCS expression and drug resistance in breast carcinoma
      cells. METHODS: Two GCS gene-specific siRNAs were designed and cloned into the
      expression vector pSUPER to generate the plasmids pSUPER-GCS1 and pSUPER-GCS2.
      Human adriamycin (ADM)-resistant breast carcinoma cells of the line MCF-7/ADR and
      human adriamycin-sensitive breast carcinoma cells of the line MCF-7 were cultured
      and transfected with pSUPER-GCS1, pSUPER-GCS2, and blank vector pSUPER as
      controls. The expression of GCS mRNA was assayed by RT-PCR and the expression of
      GCS protein was observed by flow cytometry. The 50% inhibition concentration of
      ADM on MCF-7/ADR cells was evaluated by MTT method. Flow cytometry was performed
      to determine the ratio of apoptosis. RESULTS: Double enzyme digestion analysis
      and DNA sequencing confirmed that pSUPER-GCS1 and pSUPER-GCS2 were successfully
      constructed. The GCS protein positive rate of the MCF-7/ADR cells 48 hours after
      transfection with pSUPER-GCS1 and pSUPER-GCS2 were 8.3% +/- 1.0% and 9.2% +/-
      0.8% respectively, significantly lower than that before transfection (68.3% +/-
      0.6%), with a inhibition rate of 89.4% and 88.5% respectively (both P < 0.01).
      Forty-eight hours after transfection with pSUPER-GCS1 and pSUPER-GCS2, the
      relative reversal rates of sensitivity to ADM of the MCF-7/ADR cells were 93.7%
      and 91.6%. Flow cytometry showed that the apoptotic rate of the MCF-7/ADR cells
      was 0.80 +/- 0.06 before transfection, 15.38 +/- 1.16 after transfection with
      pSUPER-GCS1 and 13.92 +/- 1.73 after transfection with pSUPER-GCS2 (both P <
      0.05), and was 0.87 +/- 0.12 in the cells transfected with blank vector (P >
      0.05). CONCLUSION: A GCS-specific small interfering RNA expression vector has
      been constructed successfully that suppresses the GCS expression and reverses the
      multidrug resistance in breast carcinoma cells by increasing the ratio of
      apoptosis in drug-resistant cells.

PMID- 15949330
TI  - [Allogeneic umbilical cord blood stem cell transplantation in Duchenne muscular
      dystrophy].
AB  - OBJECTIVE: To study the feasibility of treatment of Duchenne muscular dystrophy
      (DMD) with umbilical cord stem cell transplantation. METHODS: HLA matching was
      conducted for a 11-year-old DMD boy with family history was underwent umbilical
      cord blood stem cell transplantation and a sample of umbilical cord stem cells
      with 5 matched HLA sites was found in the cord blood bank with 27.32 x 10(8)
      nucleated cells, about 2.6 times that of the treatment dosage for him. After
      pretreatment with busulfan 14 mg/kg.d, cyclophosphamide 50 mg/kg.d, and rabbit
      anti-human thymocyte globulin 10 mg/kg.d, the allogeneic cord blood stem cells
      were transplanted intravenously. Cyclosporin A, methylprednisolone and MMF were
      used after the transplantation so as to prevent graft versus host reaction.
      Prostaglandin E1 was used to prevent Budd-Chiari syndrome, and ganciclovir was
      used to prevent cytomegalovirus infection. At the same time, Gran, granulocytic
      cell stimulating factor, and gammaglobulin were also used. Biochemistry test,
      including serum creatine kinase (CK), was conducted. Evidence of reconstruction
      of blood making, including conversion of blood type, was observed. PCR-STR
      analysis was used to observe the status of implantation of the donor umbilical
      cord blood stem cells. RESULTS: (1) 12 days after transplantation, the white
      blood cells (WBC) of peripheral blood were 0.5 x 10(9)/L, 14 days after, the
      numbers of WBC and neutrophils were 1.0 x 10(9)/L and 0.6 x 10(9)/L respectively.
      In 37 days, granulocytic cell stimulating factor was no more used, the peripheral
      blood WBC fluctuated around 3.34 approximately 12.2 x 10(9)/L. In the 27th day,
      the number of blood platelets was more than 20 x 10(9)/L and hemoglobin rose to
      88 g/L. On the 24th day red blood cells transfusion was stopped. (2) In the 42nd
      day, the blood type of the patient transformed from type A before transplantation
      to type AB (the blood type of transplanted stem cells is type B). (3) PCR-STR
      test of the peripheral blood made 17, 26, and 42 days after transplantation
      showed that the gene type of the patient was mixed mosaic: The ratio of donor
      gradually increased from 40% approximately 45% to 55% approximately 65%. (4) In
      the 38th day I degrees GVHD appeared. (5) serum CK level declined from 6000 U/L
      to 600 approximately 2200 U/L. (6) In the 42nd day, physical examination revealed
      obviously improvement in walking, turning the body over, and standing up.
      CONCLUSION: This is first case of prospective clinical transplantation on DMD by
      allogeneic cord blood stem cell. Umbilical cord stem cell transplantation helps
      re-build blood-making function, and improve locomotive function with a mild GVHD
      reaction. The genotype of rebuilt blood is mosaic but the ratio of gene mosaic
      gradually turn from recipient gene type > donor gene type to recipient gene type
      < donor gene type. The serum CK level decreases significantly after
      transplantation, which may slow down the necrosis of muscle cell. DMD patient
      will be benefited by stem cell transplantation.

PMID- 15949331
TI  - [Specific antibodies against the nucleocapsid protein and S1 domain of spike
      glycoprotein in patients with severe acute respiratory syndrome].
AB  - OBJECTIVE: To explore the laws of the appearance of the specific serum antibodies
      against the nucleocapsid (N) protein and the S1 domain of spike (S) glycoprotein
      in patients with severe acute respiratory syndrome (SARS) and to evaluate the
      value of these two proteins to be used as diagnostic makers for SARS. METHODS:
      The serum samples of 86 patients with SARS confirmed clinically and
      serologically, 31 males and 55 females, aged 9 approximately 86, with the course
      of disease of 1 approximately 81 days, and 745 healthy persons were collected
      during the course. The specific immunoglobulin G (IgG) against N protein, IgG
      against S1 domain of S protein, and the SARS-CoV IgG in these sera were detected
      by ELISA. RESULTS: The positive rates of anti-N-IgG, anti S1-IgG, and anti-SARS
      CoV IgG were 14% (6/44), 5% (2/44), and 14% (6/44) respectively in the first week
      of the course of disease, 56% (10/18), 39% (7/18), and 56% (10/18) respectively
      in the second week, and 100% (24/24), S1-IgG 83% (20/24), and 100% (24/24)
      respectively in the third week. The agreement rates of the results of anti-N-IgG
      and anti-s1-IgG with that of the anti-SARS-CoV IgG were 88% (76/86) and 83%
      (71/86) respectively. The anti-SARS-CoV IgG positive rate in the healthy persons
      was 1.88% (14.745). CONCLUSION: The N protein and S1 protein may be used as
      antigens in the development of serological assay for detection of SARS-CoV
      infection.

PMID- 15949332
TI  - [Evaluation the antimycotic activity of itraconazole in human stratum corneum
      with vitro fungi cultivation].
AB  - OBJECTIVE: To establish a new model to evaluate the antifungal activity of
      antimycotics. METHODS: Twenty-one healthy adult volunteers without clinically
      significant differences in demographic characteristics, hydration status of the
      skin, and sebum excretion were randomly divided into two groups: group 1
      receiving 200 mg itraconazole bid for 1 week, and group 2 receiving itraconazole
      200 mg qd for 1 weeks. Stratum corneum stripping was taken from the forearm skin
      at days 0, 1, 4, 7, 10, 14, 21, 28, and 35. Spores of selected fungi
      (Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum canis) were
      deposited and cultured on the center of the stratum corneum stripping. After 1
      week culture the stratum corneum stripping was staining by PAS, and the area
      covered by dermatophyte was measured by corneofungimetry and computerized
      assisted image analysis so as to calculate the inhibitory effect of the oral
      antifungal agents administered. RESULTS: All three dermatophytes grew on the
      stratum corneum stripping, the area covered by the dermatophyte was dense before
      administration of antifungal agent, and decreased gradually after the
      administration of drug, and to the least on the seventh day (P < 0.01), however,
      the area covered by the dermatophyte began to increase since the tenth day, and
      reach the biggest on the thirty-fifth day. Itraconazole at two different dosages
      showed significant activity against these 3 dermatophytes without significant
      difference between the two groups (all P > 0.05). CONCLUSION: The ex vivo growth
      environment of dermatophyte on human stratum corneum is very similar to that of
      human milieu interne. Itraconazole displays a high antidermatophyte activity in
      human stratum corneum. Corneofungimetric bioassay is a new method between in
      vitro trial and in vivo effect.

PMID- 15949333
TI  - [Serum levels of several chemokines in patients with rheumatoid arthritis].
AB  - OBJECTIVE: To explore the role of several chemokines in rheumatoid arthritis (RA)
      and their clinical significance. METHOD: ELISA was used to detect the serum
      levels of interleukin (IL)-8, interferon-gamma inducible protein (IP)-10, and
      RANTES in 58 active RA patients, 29 clinically remissive RA patients, 21
      osteoarthritis (OA) patients, and 30 healthy volunteers. Clinical data of these
      patients were compared between different groups. RESULTS: The serum levels of IL
      8, IP-10 and RANTES in the active RA patients were significantly higher than
      those of the healthy controls and OA patients. The serum level of IP-10 of the
      active patients was higher than that of the clinically remissive patients. The
      index IL-8/IP-10 x RANTES/IP-10 of the active patients was higher than that of
      the healthy controls (P = 0.01). The serum RANTES level was positively correlated
      with erythrocyte sedimentation rate, C-reactive protein, platelet count, and
      numbers of swollen joints, and was negatively correlated with the hemoglobin
      level. The serum level of IP-10 was negatively correlated with X-ray image grade
      of hand and wrist joints. CONCLUSION: The serum levels of IL-8, IP-10 and RANTES
      significantly increase in active RA. The level of RANTES may be a useful
      additional marker for disease activity and the level of IP-10 can be used as an
      index of prognosis.

PMID- 15949334
TI  - [Left ventricular function in congenital hypothyroidism neonates before and after
      thyroxine substitution therapy].
AB  - OBJECTIVE: To evaluate left the systolic and diastolic functions in neonates with
      congenital hypothyroidism (CH) as well as the effect of thyroxine substitution
      therapy on left ventricular function and its correlation with thyroid hormones
      serum levels. METHODS: M-mode echocardiography was used to examine the left
      ventricular ejection fraction (LVEF) and left ventricular fractional shortening
      (LVFS), pulse wave Doppler was used to examine the peak early diastolic mitral
      inflow velocity (E(m)) and peak late diastolic mitral inflow velocity (A(m)),
      quantitative tissue velocity imaging (QTVI) was used to examine the systolic peak
      mitral annular velocity (s(m)), early diastolic peak mitral annular velocity
      (E(m)), and the late diastolic peak mitral annular velocity (a(m)), and tissue
      tracking imaging (TTI) was used to detect the systolic mitral annular
      displacement (MAD) in 40 neonates with congenital hypothyroidism aged 15-28 days
      before and after 1-month levothyroxine substitution treatment. Thirty normal
      neonates were used as controls. Chemiluminescent immunoassay was used to measure
      the TT(3), TT(4) and TSH levels. Correlation analysis was also made between the
      ventricular function parameters and the serum TT(3), TT(4), and TSH levels.
      RESULTS: The left systolic function parameters (LVEF, s(m), MAD, E(m) and e(m))
      was 0.61 +/- 0.08, 2.60 cm/s +/- 0.60 cm/s, 0.29 cm +/- 0.06 cm, 0.59 m/s +/-
      0.12 m/s and 2.72 cm/s +/- 1.43 cm/s respectively, in CH group, and 0.67 +/-
      0.06, 3.25 cm/s +/- 0.51 cm/s, 0.41 cm +/- 0.08 cm, 0.72 m/s +/- 0.11 m/s and
      4.51 cm/s +/- 1.23 cm/s in control group (P < 0.01). Left function in CH neonates
      before treatment were all lower than those of the controls (P < 0.01), which
      significantly increase after 1-months L-T(4) substitution therapy, 0.69 +/- 0.05,
      3.46 cm/s +/- 0.64 cm/s, 0.45 cm +/- 0.08 cm, 0.82 m/s +/- 0.17 m/s and 5.09 cm/s
      +/- 1.37 cm/s, (P < 0.01). Those parameters were positively correlated with TT(4)
      serum levels (P < 0.01), and were negatively correlated with TSH (all P < 0.01).
      In particular, MAD, sm, E(m), and em were highly correlated with serum TT(4) and
      TSH (r = 0.667, 0.538, 0.478, and 0.599 respectively, all P < 0.001;and r = 
      0.670, -0.521, -0.490, and -0.583 respectively, all P < 0.001). CONCLUSION:
      Neonates with CH have lower left systolic and diastolic functions. Early L-T(4)
      substitution therapy can reverse these changes.

PMID- 15949335
TI  - [Expression of enhanced green fluorescent protein in rat brain transduced by
      recombinant adeno-associated viruses type 1 and type 2].
AB  - OBJECTIVE: To explore the expression of enhanced green fluorescent protein (EGFP)
      transduced into the brain via recombinant adeno-associated virus (rAAV) type 1
      and rAAV type 2 vectors so as to select the better rAAV serotype and feasible
      gene transfer route to central nervous system (CNS). METHODS: Twenty-four SD male
      adult rats were randomly divided into 4 equal groups: rAAV1 intra-hippocampus
      injection group, rAAV1 intra-ventricular injection group, rAAV2 intra-hippocampus
      injection group, and rAAV2 intra-ventricular injection group to be injected
      stereotactically with titer and volume matched rAAV1-EGFP and rAAV2-EGFP vectors
      respectively. The rats were sacrificed respectively 2 and 4 weeks after injection
      and their brains were removed to be made into serial frozen coronal sections.
      Fluorescence microscopy was used to observe the expression of EGFP in the brain
      and to calculate the expression volume of EGFP in different parts of the brain.
      RESULTS: Two weeks after injection EGFP was expressed in a small amount or not
      expressed in all groups. Four weeks after injection the EGFP expression volume
      were (7.00 +/- 0.98) mm(3) and (0.81 +/- 0.28) mm(3) in the rAAV1 and rAAV2 intra
      hippocampus injection groups respectively (P < 0.01), and were (12.72 +/- 0.28)
      mm(3) and (0.24 +/- 0.13) mm(3) in the rAAV1 and rAAV2 intra-ventricular
      injection groups respectively (P < 0.001). CONCLUSION: As gene-transducing vector
      in CNS rAAV1 is superior to rAAV2. High expression can be achieved by intra
      ventricular injection with rAAV1 vectors.

PMID- 15949336
TI  - [Vascular endothelial growth factor shRNA mediated by pEGFP-H1 vector plasmid
      effectively inhibits glioma proliferation: an experimental study].
AB  - OBJECTIVE: To investigate the inhibitory effects of RNA silencing via plasmid
      mediated vascular endothelial growth factor (VEGF) shRNA on proliferation of
      glioma cells in vitro and in vivo. METHODS: pEGFP-H1/VEGF vector plasmid
      containing enhanced green fluorescent protein (EGFP) gene and expressing VEGF
      shRNA was constructed. The EGFP expression was detected by fluorescent microscopy
      and flow cytometry. Glioma cells of the line U251 were cultured and divided into
      3 groups to be transfected with blank vector, pEGFP/H1plasmid, and pEGFP-H1/VEGF
      respectively. RT-PCR was used to detect the mRNA expression of VEGF in the
      supernatants of the culture media. The protein expression of VEGF in the
      supernatant was detected by ELISA. The cell growth was observed with MTT method.
      Fifteen nude rats were randomly divided into 3 equal groups to be transplanted
      with U251 cells and pEGFP-H1, U251 cells and pEGFP-H1/VEGF, and U251 cells only
      as blank control group. The growth of glioma was observed every day. 30 days
      after the rats were killed and the tumors were taken out to be examined. RESULTS:
      Twenty-four hours after transplantation, fluorescence microscopy showed great
      numbers of U251 cells that expressed green fluorescence in both the pEGFP-H1
      group and pEGFP-H1/VEGF group. Flow cytometry showed that the rates of green
      fluorescent protein positive cells were 68.37% and 65.29% in these 2 groups (P >
      0.05). MTT method showed no significant difference in the effect on cell growth
      among the 3 groups (all P > 0.05). PCR showed that the VEGF mRNA expression was
      significantly inhibited in the pEGFP-H1/VEGF group in comparison with those in
      the blank control group and the group transfected with pEGFP-H1 (both P < 0.05).
      The concentration of VEGF protein of the U251 cells transfected with pEGFP
      H1/VEGF was 530 ng/L +/- 118 ng/L, significantly lower than those of the control
      group (2571 ng/L +/- 572 ng/L) and the group transfected with pEGFP-H1 (2402 ng/L
      +/- 310 ng/L, by 77.9%) (both P < 0.01). Tumor could be touched 13 days after
      transplantation in the rats of pEGFP-H1/VEGF group, markedly later than in the
      other 2 groups. Thirty days after, the weight and volume of tumor were 0.5 g +/-
      0.4 g and 401 mm(3) +/- 272 mm(3) respectively in the rats of pEGFP-H1/VEGF
      group, both significantly lower than those of the control group and pEGFP-H1
      group (1.7 g +/- 0.4 g and 1573 mm(3) +/- 330 mm(3); and 1.5 g +/- 0.7 g and 1430
      mm(3) +/- 382 mm(3)) (all P < 0.01). CONCLUSION: The successfully constructed
      shRNA targeting at VEGF efficiently decreases the VEGF expression of the glioma
      cells in vitro and suppresses the growth of glioma cells in vivo.

PMID- 15949337
TI  - [Influence of nitric oxide on heme oxygenase/carbon monoxide system in
      hippocampus of febrile seizures rats].
AB  - OBJECTIVE: Febrile seizures (FS) are the most common type of seizure disorders.
      Studies have found that there have respective changes of heme oxygenase (HO)/CO
      system and nitric oxide synthase (NOS)/NO system during FS. The present study was
      to explore the influence on expression of HO-1 mRNA and protein and content of CO
      after recurrent FS by NOS inhibitor N(omega)-nitro-L-arginine Methyl ester (L
      NAME), in order to demonstrate a regulating role in HO/CO system by NO. METHODS:
      Forty-eight SD rats were randomly divided into 3 equal groups: FS group,
      undergoing intraperitoneal injection of normal saline (NS) and then bath in 45.2
      degrees C hot water for 5 minutes every other day for 10 times, FS + L-NAME
      group, undergoing intraperitoneal injection of NOS inhibitor N(omega)-nitro-L
      arginine methyl ester (L-NAME) and then FS for 10 times, and control group,
      undergoing intraperitoneal injection of NS and then bath in 37.0 degrees C water.
      Twenty-four hours after the last bath blood was collected from the abdominal
      cardinal vein to measure the concentrations of plasma nitric oxide and carbon
      monoxide with spectrophotometer. The brains were taken out to be made into frozen
      slices to undergo HO-1 in situ hybridization to measure the mRNA expression of HO
      1. The hippocampus was taken out to undergo Western blotting to measure the
      expression of HO-1 protein. RESULTS: The plasma CO concentration was higher by
      94.5% in the FS group in comparison with that in the control group (P < 0.01).
      The plasma CO concentration of the FS + L-NAME group was higher by 63.18% than
      that of the control group (P < 0.05) and lower by 16.14% than in the FS group (P
      < 0.05). The HO-1 mRNA expression was significantly higher in the FS group than
      in the control group. The HO-1 mRNA expression of the in hippocampal neurons of
      the L-NAME was lower than that of the FS group, however, still higher than that
      of the control group. Western blotting showed that HO-1 protein was expressed in
      all 3 groups; the HO-1 protein expression of the FS group was higher by 208% than
      that of the control group; and the HO-1 protein expression of the FS + L-NAME
      group was higher by 115% than that of the control group (P < 0.01) and lower by
      30.19% than that of the FS group (P < 0.01).

PMID- 15949338
TI  - [A study on the regulatory mechanisms of mitogen-activated protein kinase
      phosphatase-1 in hypoxia inducible factor-1 trans-activation].
AB  - OBJECTIVE: To investigate the regulatory mechanisms of mitogen-activated protein
      kinase phosphatase-1 (MKP-1) in hypoxia inducible factor (HIF)-1 trans
      activation. METHODS: (1) Gastric cancer cells of the line SGC7901 were cultured,
      then continued to be cultured in hypoxic environment, and was lysed. The
      supernatant was collected. Western blotting was used to detect the content of
      total extracellular signal-regulated kinase (ERK) and phosphorylated ERK. (2)
      Another SGC7901 cells were cultured with PD98059, inhibitor of ERK passway, or
      SB203580, inhibitor of p38 passway, in the same manner as above-mentioned. Dual
      luciferase reporter (DLR) was used to detect the luciferase activity so as to
      measure the HIF-1 trans-activation. (3) siRNA vector U6M2 plasmid against MKP-1
      mRNA was constructed. In another experiment SGC7901 cells were cultured and U6M2
      and blank vector U6 were transfected into the cells respectively. 24 hours later,
      the cells were cultured in hypoxic environment with added PD98059 of different
      concentrations for 12 hours. Dual luciferase reporter (DLR) was used to detect
      the luciferase activity HIF-1 trans-activation. (4) Another SGC7901 cells were co
      transfected with U6M2, pGL-3SV40HRE vector containing promoter SV40, and pRL-TK
      (internal control vector). Then PD98059 was added, the cells were lysed, and the
      activity of fluorescein was tested. (5) SGC7901 cells were cultured, transfected
      with UdM2 or U6 respectively, and 24 hours later cultured under hypoxia with
      PD98059 of different concentrations for 12 hours. ELISA was used to examine the
      VEGF protein concentration in the culture fluid. RESULTS: (1) The content of
      phosphorylated ERK in the SGC7901 cells increased along with the time of hypoxia,
      peaked at the 12th hour, and then decreased. However, there was no difference in
      total ERK expression. (2) After 12 hours of hypoxia, different concentrations of
      PD98059 inhibited the luciferase activity, however, SB203580 of different
      concentrations had no effect. (3) 24 hours after transfection, the expression of
      phosphorylated form of ERK in the SGC7901cells transfected with siRNA plasmid
      against MKP-1 mRNA was higher compared with that in cells transfected with blank
      vectors after 12 hour of exposure to hypoxia. (4) PD98059 inhibited the
      luciferase activity either in U6 cells or in U6M2 cells. Notably, when the
      PD98059 concentration was above 50 micromol/L, there was no difference in HIF-1
      activity between the U6 and U6M2 cells. (5) PD98059 of different concentrations
      all inhibited the VEGF expression either in U6 cells or in U6M2 cells, and when
      the concentration of PD98059 was over 50 micromol/L there was no difference in
      VEGF expression level between the U6 cells and the U6M2 cells. CONCLUSION: In
      SGC7901 cells, the function of MKP-1 is involved in regulation of HIF-1 trans
      activation via inactivation of the ERK pathway.

PMID- 15949339
TI  - [Experimental study of E-box, a transcriptional suppressor element in gamma-GCS
      gene].
AB  - OBJECTIVE: To validate that the E-box element in the -745-705 region of rat gamma
      GCS catalytic subunit gene (GCLC gene), already found to be a negative regulatory
      region, is an important transcriptional suppressor element. METHODS:
      Electrophoretic mobility shift assays (EMSA) and antibody supershift assay were
      used to confirm the specific binding of USF, a transcription factor that binds
      the regulatory sequence -745 - 705, and E-box element. Rat alveolar epidermal
      cells of the line CCL-149 were cultured and then divided into 4 groups: group 1
      to be transfected with GCLC-Luc, group 2 to be co-transfected with pGCLC-Luc and
      pCMV-USF1, group 3 to be co-transfected with pGCLC-Luc and pCMV-USF2, and group 4
      to be co-transfected with pGCLC-Luc and blank vector pCMV. Recombinant retrovirus
      vector PLXSN-USF1 and recombinant retrovirus vector PLXSN-USF2 were constructed.
      Another CCL-149 cells were divided into 4 groups: group A to be infected with
      recombinant USF1 virus, group B to be infected with recombinant USF2 virus, group
      C to be infected with blank vector, and group D not to be infected with any
      plasmid. Western blotting was used to detect the concentrations of GCLC protein.
      RESULTS: EMSA showed that only the probes with complete E-box element could be
      bound by the USFs. Supershift assay showed that the transcription factor binding
      the probe was USF. The luciferase activity of the CCL-149 cells co-transfected
      with pCMV-USF1/USF2 and GCLC-Luc were decreased by 66.4% and 63.2% respectively
      in comparison with those transfected with GCLC-Luc only (both P < 0.05) and
      decreased by 54.5% and 61.1% respectively in comparison with those of the cells
      of the blank vector group (both P < 0.05). Western blotting showed that the
      expression of GCLC protein of the CCL-149 cells transfected with PLXSN-USF1 and
      PLXSN-USF2 were decreased in comparison with that of the control cells.
      CONCLUSION: The interaction between E-box and USF suppresses the expression of
      GCLC gene. E-box is an important transcriptional suppressor element of gamma-GCS
      gene.

PMID- 15949340
TI  - [Assessment of the efficacy of endoscopy transnasal transsphenoidal assisted
      microsurgery of pituitary tumor ].

PMID- 15949341
TI  - [Gene expression and changes of plasma level of leukocyte matrix
      metalloproteinase-9 before and after cardiopulmonary bypass].

PMID- 15949342
TI  - [Effects of expression of thymidine phosphorylase induced by gamma-interferon on
      regulation of antineoplastic activity of fluorouracil on colonic cancer].

PMID- 15949347
TI  - [The value of lung volume reduction in treatment of late-stage emphysema].

PMID- 15949348
TI  - [Exploration and innovation to raise the high level medical talented persons].

PMID- 15949349
TI  - [Quality of life of patients after esophagogastrostomy combined with lung volume
      reduction surgery].
AB  - OBJECTIVE: To evaluate the effect of lung volume reduction surgery (LVRS)
      combined with esophagogastrostomy in thorax on quality of life of the patients
      with severe emphysema combined with esophageal or cardiac carcinoma. METHODS:
      Eighteen patients suffering from esophageal or cardiac carcinomas and severe
      emphysema with severely impaired respiratory function and low quality of life
      underwent resection of carcinoma and esophagogastrostomy in thorax. And then,
      same side LVRS was performed using TLC75 stapler. All staple lines were
      buttressed with bovine pericardial strips. Quality of life was evaluated before
      operation and every 3 months up to one year postoperatively by using the Short
      form 36 (SF-36) health questionnaire. RESULTS: The volumes of resected pulmonary
      tissues, weighing (62.2 +/- 9.6) g, accounted for 25% - 30% of the total volume
      of the same side lung parenchyma. All the cases went through successfully the
      perioperative period without hospital mortality. Postoperative hospital stay
      averaged 19.7 +/- 4.8 days (15 to 23 days). All of the functions included in the
      SF-36 were improved (P < 0.01 or P < 0.05). CONCLUSION: Esophagogastrostomy in
      thorax combined with LVRS significantly benefits the patients with severe
      emphysema and esophageal or cardiac carcinoma in terms of long-term quality of
      life.

PMID- 15949350
TI  - [Laparoscopic treatment of esophageal hiatal hernia: analysis of 11 cases].
AB  - OBJECTIVE: To investigate the effect and safety of laparoscopic treatment in
      patients with esophageal hiatal hernia. METHODS: Eleven patients with esophageal
      hiatal hernia, 9 males and 2 females, with the mean age of 56, accepted
      laparoscopic treatment. Two cases were treated by hernia repair merely and 9
      cases were treated by hernia repair and fundoplication (Nissen's operation) one
      of which accepted laparoscopic cholecystoectomy at the same time. RESULTS: All
      patients were treated successfully. The operation time was 2.5 hours (1.5 - 5
      hours) and the blood loss was between 20 - 200 ml. The patients began to accept
      liquid diet 24 - 36 hours after operation. There was no postoperative
      complication and all the clinic symptoms disappeared. The mean hospitalization
      time was 8 days (6 - 15d). CONCLUSION: Laparoscopic treatment of esophageal
      hiatal hernia provides a safe and minimal invasive procedure.

PMID- 15949351
TI  - [The value of postoperative arterial infusion chemotherapy in patients with T3
      esophageal squamous carcinoma after radical surgery].
AB  - OBJECTIVE: To studying the porgnostic factors after curative esophagetomy for the
      thoracic segment T3 esophageal after radical surgery. METHODS: 190 patients
      suffering from T3 squamous carcinoma of lower thoracic esophagus who underwent
      radical surgery from January 1990 to January 1999, 158 males and 32 females, aged
      62.98 (40 approximately 81), were divided into 2 groups: 108 patients
      (experimental group, T3N0M0 56 cases and T3N1M0 52 cases) underwent surgery and
      arterial infusion (cisplatin 80 mg/m(2) and fluorouracil (800 mg/m(2)) with or
      without epirubicin since 3 approximately 4 weeks postoperatively, the interval of
      each periods is 4 - 6 weeks. and the other 82 patients (T3N0M0 48 cases and
      T3N1M0 34 cases) underwent surgery only. Fifty-six out of the 108 cases in the
      experimental group (T3N0M0 26 cases and T3N1M0 30 cases) underwent 3 periods of
      chemotherapy for less than 3 periods of chemotherapy with an interval between 2
      periods of 4 approximately 6 weeks, and the other 52 patients (T3N0M0 30 cases
      and T3N1M0 22 cases) underwent chemotherapy for 3 periods or over. All cases were
      followed up for more than 5 years. Kaplan-Meier survival curve was used to
      analyze the survival rate. Cox regression model was used to analyze the
      influencing factors of prognosis. RESULTS: There was no significant difference in
      the overall long-term survival rate between the experimental group and control
      group, however, the survival rate of those receiving 3 periods of chemotherapy
      and over was significantly higher than those receiving less than 3 periods of
      chemotherapy Lymph node metastatic status was an important factor in prognosis of
      esophageal squamous carcinoma. CONCLUSION: Without severe side effects,
      postoperative chemotherapy by transcatheter arterial infusion prolongs the
      survival rate of the patients with esophageal squamous carcinoma who have been
      previously treated by radical surgery.

PMID- 15949352
TI  - [Expression of MLRQ subunit gene of NADH oxidoreductase and its clinical
      significance in malignant tumors of digestive system].
AB  - OBJECTIVE: To study the differential expression and possible role of MLRQ subunit
      gene of nicotinamide adenine dinucleotide reduced (NADH) oxidoreductase in
      malignant tumors of digestive system. METHODS: Specimens of cancerous tissues and
      matched adjacent normal tissues resected during operation or biopsy: 38 pairs of
      specimens of esophageal carcinoma, 7 pairs of specimens of cardiac carcinoma, 14
      pairs of specimens of gastric carcinoma, 11 pairs of specimens of colon
      carcinoma, and 7 pairs of specimens of liver carcinoma underwent PCR test and
      Northern hybridization to detect the differential expression of MLRQ subunit gene
      of NADH oxidoreductase. RESULTS: (1) Overexpression of MLRQ subunit gene was
      found in 31 of the 38 pairs of specimens of esophageal carcinoma (81.6%), 4 of
      the 7 pairs of specimens of cardiac carcinoma (57.1%), 12 of the 14 pairs of
      specimens of gastric carcinoma (85.7%), 4 of the 7 pairs of specimens of colon
      carcinoma (65.6%), and 7 of the 11 pairs of specimens of liver cancer (57.1%). No
      significant difference among different cancers was observed by X(2) test (all P >
      0.05). (2) The up-regulation of MLRQ subunit was not correlated with clinic
      stage, infiltration degree, lymphatic metastasis, and differentiation of tumor
      (all P > 0.05). CONCLUSION: MLRQ subunit gene is up-regulated in the malignant
      tumors of digestive system.

PMID- 15949355
TI  - [A pig model of myocardial infarction by intracoronary embolization with gelatin
      sponge].
AB  - OBJECTIVE: We produced a large-animal model of myocardial infarction induced by
      transcatheter embolization of the left coronary artery using a gelatin sponge.
      METHODS: Seven pigs underwent transcatheter embolization of the left anterior
      descending artery (LAD) using gelatin sponge to produce anteroapical myocardial
      infarction (MI). 4 weeks later, Echocardiography, Coronary angiography and
      Pathology was performed, and the data were compared with those of the control
      group (n = 6). RESULTS: The procedure mortality was 1 of 7. In the MI group, the
      LV end-diastolic dimension increased (control versus MI: 37.0 mm +/- 3.4 mm and
      50.8 mm +/- 6.1 mm, P < 0.01), the ejection fraction (EF) decreased (control
      versus MI: 62.3% +/- 2.9% and 36.6% +/- 2.1%, P < 0.001). Coronary angiography
      revealed the LAD remained occluded. The postmortem specimen showed a transmural
      MI scar in the anteroseptal and apical regions in the MI group and the LV volumes
      at 30 mm Hg were 81.4 ml +/- 4.3 ml, the scar areas were 18.4% +/- 1.6% of total
      left ventricular free wall and the scar thickness was 3.5 mm +/- 0.8 mm.
      Histologic samples in the MI group stained with Masson's trichrome showed massive
      fibrosis in the border zone and patchy fibrosis in the remote region in the LV
      free wall, whereas the control group showed no fibrosis. CONCLUSION: This pig
      model of myocardial infarction is reliable, reproducible, and similar to the
      human condition, amenable to investigate other investigation.

PMID- 15949354
TI  - [Perioperative detection of MAGE-1mRNA and AFP mRNA in peripheral blood of
      patients with hepatocellular carcinoma: relationships with recurrence].
AB  - OBJECTIVE: To detect MAGE-1 mRNA and AFP mRNA in the peripheral blood of patients
      with hepatocellular carcinoma (HCC) perioperatively, and explore their
      relationships with recurrence. METHODS: Peripheral blood from 45 patients with
      HCC, obtained perioperatively, was tested for the presence of MAGE-1 mRNA and AFP
      mRNA by nested RT-PCR. All patients were followed for metastatic recurrence for
      average 11 months after surgery. The peripheral blood from 22 patients with
      hepatitis B and cirrhosis, 11 patients with hepatic hemangioma, 12 patients with
      metastatic liver cancer and 20 healthy volunteers served as control. RESULTS:
      Four of the twelve (33.3%) metastatic hepatic cancer patients were positive for
      MAGE-1 mRNA, and three of the twenty-two (13.6%) patients with hepatitis B and
      cirrhosis were positive for AFP mRNA while the other controls kept negative in
      their peripheral blood. Detection rates for MAGE-1 mRNA/AFP mRNA in the
      peripheral blood of patients with HCC were 42.2%/51.1% before operation,
      20%/24.4% seven days after surgery, and 15.6%/22.2% 28 days later respectively.
      In chi-square analysis, detection of peripheral-blood MAGE-1 mRNA and AFP mRNA 28
      days after surgery indicated metastatic recurrence. Furthermore, the two-marker
      detection had a higher specificity for prediction of metastatic recurrence than
      single marker detection. CONCLUSION: Combined detection of cancer-specific MAGE-1
      mRNA and hepatocyte-specific AFP mRNA by nested RT-PCR in the peripheral blood of
      patients with HCC 28 days after surgery may be useful for the prediction of
      metastatic recurrence.

PMID- 15949356
TI  - [Influencing factors for the curative effects of short-term continuous
      subcutaneous insulin infusion on newly diagnosed type 2 diabetes].
AB  - OBJECTIVE: To investigate the effects of short-term continuous subcutaneous
      insulin infusion (CSII) on newly diagnosed type 2 diabetes and to identify the
      influencing factors for the curative effects of CSII. METHODS: 138 newly
      diagnosed type 2 diabetic patients with fasting plasma glucose > 11.1 mmol/L were
      treated with CSII for 2 weeks. Intravenous glucose tolerance test (IVGTT) was
      performed before and after CSII. The target of glycemic control were fasting
      blood glucose < 6.1 mmol/L and postprandial blood glucose (PBG) < 8.0 mmol/L. The
      age, body mass index (BMI), fasting and postprandial plasma glucose, hemoglobin
      A(1C) (GHbA(1C)), Homa beta, Homa IR, area under the curve of insulin (AUC)
      during IVGTT were compared between the good glycemic control group and the
      inadequate glycemic control group. RESULTS: After 2 weeks' CSII treatment, good
      glycemic control was achieved in 126 patients (group A) but not in the remaining
      12 patients (group B). There were no differences in age, BMI, postprandial plasma
      glucose, GHbA(1C), and Homa IR between the two groups before and after CSII
      treatment. But the fasting plasma glucose was higher and Homa B was lower in
      group B than in group A before CSII treatment. The DeltaAUC (AUC after CSII
      subtracted from that before CSII) representing the recovery of beta-cell function
      was much greater in group A than in group B. The insulin dose of group B was
      significantly higher than that of the good glycemic control group. CONCLUSION:
      More severe hyperglycemia and relative beta-cell function deficiency may be the
      main reasons responsible for not achieving good glycemic control in newly
      diagnosed type 2 diabetic patients with short-term intensive CSII treatment.

PMID- 15949357
TI  - [Impact of hypertension on angiogenesis in the tissues of benign prostatic
      hyperplasia].
AB  - OBJECTIVE: To investigate the impact of primary hypertension on angiogenesis in
      the tissues of benign prostatic hyperplasia (BPH). METHODS: Immunohistochemistry
      was carried out to examine the expression of CD34, so as to calculate the
      microvassel density (MVD), and the expression of vascular endothelial growth
      factor (VEGF) in the tissues of prostatic gland, resected during operation, of 50
      simple BPH patients, aged 68.3 (56 approximately 83), and 50 patients with BPH
      with hypertension, aged 69.0 (55 approximately 91) with a course of hypertension
      of 16.5 +/- 11.9 years (1 - 41 years). RESULTS: The MVD of the simple BPH group
      was 23.1 +/- 9.2, significantly lower than that of the BPH complicated with
      hypertension group (28.2 +/- 9.5, P < 0.01), especially the BPH complicated with
      hypertension group with a course >/= 15 years (31.3 +/- 8.5). The MVD of the BPH
      complicated with hypertension group with a course >/= 15 years was significantly
      higher than that of the BPH complicated with hypertension group with a course <
      15 years (25.7 +/- 9.7, P < 0.05). The VEGF positive rate of the stroma of the
      simple BPH group was 46.0%, significantly lower than that of the BPH complicated
      with hypertension group (66.0%, P < 0.05), especially that of the BPH complicated
      with hypertension group with a course >/= 15 years (81.8%). The VEGF positive
      rate of the stroma of the BPH complicated with hypertension group with a course
      >/= 15 years was significantly higher than that of the BPH complicated with
      hypertension group with a course < 15 years (53.6%, P < 0.05). In the group of
      BPH with hypertension, MVD was positively correlated with the expression of VEGF
      in the stromal tissue (R = 0.11, P < 0.05). CONCLUSION: Hypertension may be
      closely related to the increased expression of VEGF in prostatic stroma. The
      increased expression of VEGF may induce angiogenesis and consequently lead to
      clinical progression of BPH in patients with hypertension.

PMID- 15949358
TI  - [Expression of different genes in transitional zone and peripheral zone of human
      normal prostate].
AB  - OBJECTIVE: To detect the expression of different genes in the transitional zone
      and peripheral zone of human normal prostate. METHODS: Seventeen specimens of
      normal prostate gland were obtained from dead kidney donors and patients
      undergoing total cystectomy. The transitional zone and peripheral zone were
      isolated. Twenty specimens of benign prostate hypertrophy (BPH) were obtained
      from patients undergoing prostatic enucleation. The periurethral significantly
      hypertrophic nodules were isolated. BioDoor Chip-40S containing 6700 clones of
      targeting gene cDNA was used to detect the gene expression. The peripheral zone
      RNA samples were labeled with cy3, and the transitional zone RNA samples labeled
      with Cy5. The genes with the ratio average (RA) < 0.5 or > 2 were identified as
      differentially expressed genes, and those with a RA < 0.2 or > 4 were identified
      as the most significantly differentially expressed genes. RT-PCR was used to
      investigate semi-quantitatively the expression of epidermal growth factor (EGF)
      mRNA in the 17 specimens of transitional zone and peripheral zone from the 17
      normal prostate glands and the 20 specimens of periurethral zone from BPH.
      RESULTS: A total of 640 genes differentially expressed in transitional zone and
      peripheral zone were screened out (comprising 269 unknown genes and 371 known
      genes), of which 294 genes were expressed in the transitional zone and 346 in the
      peripheral zone. Fourteen genes were identified as markedly differentially
      expressed, among which the EGF gene was highly expressed in the central zone, and
      the OSF-1 (osteoblast stimulating factor-1) gene was highly expressed in the
      peripheral zone. RT-PCR proved that in comparison with the expression of the
      internal marker beta-actin gene, the expression levels of EGF in the normal
      transitional zone and in the periurethral zone from BPH were markedly higher than
      that in the peripheral zone. CONCLUSION: There are differently expressed genes
      between the peripheral zone and central zone of normal human prostate, which may
      be the background of different biological behavior between these zones. EGF may
      markedly contribute to the growth of central zone of normal prostate.

PMID- 15949359
TI  - [The role of graded reoxygenation with cardiopulmonary bypass in prevention of
      reoxygenation injury and its safety].
AB  - OBJECTIVE: To investigate the role of graded reoxygenation with cardiopulmonary
      bypass (CPB) in prevention of reoxygenation injury in children with cyanotic
      congenital heart defects, and to evaluate its safety. METHODS: Twenty pediatric
      patients with cyanotic congenital heart defect were randomly divided into 2 equal
      groups according to CPB methodology: group 1, undergoing routine hyperoxic CPB
      with CPB primed and initiated at FiO(2) of 1.0, and group 2 undergoing modified
      CPB with graded reoxygenation (CPB was primed and initiated at FiO(2) of 0.21 and
      the FiO(2) was increased slowly to 30% to 60% over the next 5 to 10 minutes).
      Serum troponin 1 (TnI), S100beta protein, and malondialdehyde (MDA) were measured
      before CPB, and 1 minute, 5 minutes, and 10 minutes after CPB. Near infrared
      spectroscopy (NIRS) was applied to evaluate the cerebral oxygenated hemoglobin
      (HbO(2)) and oxidized cytochrome aa3 (CytOx) and jugular venous lactate was
      measured during the reoxygenation period. Clinical indexes were observed.
      RESULTS: Before CPB the TnI, S100beta, and MDA levels in these 2 groups were all
      normal without significant differences between them. After initiation of CPB the
      TnI, S100beta, and MDA levels in the two groups began to increase. The serum Tn1
      levels 1 minute and 5 minutes after the initiation of CPB of the group 1 were
      significant lower than those of the group 2 (both P < 0.01). The serum S100beta
      levels 1, 5, and 10 minutes after the initiation of CPB in the group 2 were all
      lower than those of the group 1 and there were significant differences between
      these 2 group 5 and 10 minutes after (both P < 0.05). The serum MDA levels 1, 5,
      and 10 minutes of the group 1 were significantly higher than those of the group 2
      (all P < 0.05). NIRS showed that HbO(2) decreased slightly because of
      hemodilution when CPB was begun, and then increased rapidly 2 minutes after the
      initiation of CPB; and CytOx decreased progressively during the reoxygenation
      period, however, without significant difference between these 2 groups. The serum
      lactate level was markedly increased 1 minute after the initiation of CPB and
      then gradually decreased through the reoxygenation period, however, without
      significant differences between these 2 groups. There was no significant
      difference between the two groups in clinical observation. CONCLUSION: Not
      damaging the cerebral aerobic metabolism, graded reoxygenation with CPB can
      reduce the extent of reoxygenation injury of routine hyperoxic CPB and is an
      easy, effective, and safe CPB strategy.

PMID- 15949360
TI  - [Diagnosis and management of primary hyperparathyrodism with urolithiasis].
AB  - OBJECTIVE: To investigate the diagnosis and management of primary
      hyperparathyroidism with urolithiasis. METHODS: The clinical data of 12 patients
      who were diagnosed with primary hyperparathyroidism with urolithiasis from
      January 1998 to June 2004 were analyzed retrospectively. RESULTS: Four male and
      five female patients were demonstrated pathologically as parathyroid adenoma,
      with a mean age of 45.7 +/- 11.8 years (26 approximately 57) and a stone history
      of 8.3 +/- 6.4 years (0.5 approximately 22). Their serum calcium and PTH level
      were elevated obviously, while serum phosphate of 66% patients were lowered. The
      positive rate and accuracy of ultrasound, CT and (99m)TC-MIBI imaging were 67%,
      100%, and 100% and 67%, 75%, 100% respectively. After resection of the
      parathyroid adenoma, the patients' serum calcium and PTH returned to normal. The
      other data of 3 cases without parathyroid adenoma. all males aged 45
      approximately 54, were also investigated. CONCLUSIONS: Serum calcium level above
      2.96 mmol/L and PTH 3.9 or more times as normal in patients with recurrent or
      bilateral urolithiasis should be suspected with primary hyperparathyroidism.
      (99m)TC-MIBI image functions best in preoperative localization of the abnormal
      gland. Parathyroidectomy is the curative approach for the disease. Stones should
      be followed up after operation and appropriate treatment should be employed when
      needed.

PMID- 15949361
TI  - [An immunofluorescence assay for the detection of SARS associated coronavirus
      antibody based on recombinant nucleocapsid antigen and its application].
AB  - OBJECTIVE: To establish a new technique for SARS-CoV antibody test to detect
      infection of severer acute respiratory syndrome (SARS). METHODS: Nucleocapsid
      gene was obtained by reverse transcription and polymerase chain reaction from a
      SARS patient and inserted into the vector pFastBacHTa expressing baculovirus.
      Insect Sf9 cells were transfected with the recombinant baculovirus expressing
      SARS nucleocapsid antigen and then cultured, fixed by acetone so as to make SARS
      specific antigen. Immunofluorescence assay (IFA) technique and plaque reduction
      neutralization test (PRNT) were used to detect 7 samples of sera of 4 newly
      diagnosed SARS patients collected in different days, 48 samples of convalescent
      sera of SARS patients, 24 serum samples of healthy person undergoing physical
      examination, and 40 serum samples from non-SARS patients with fever by double
      blind test. RESULTS: The recombinant SARS-specific antigen reacted only with SARS
      positive sera but not with normal sera. Double blind test showed that 45 of the
      46 PRNT positive sera were IFA positive with an accordance rate of 97.8%. 7
      samples of sera from 4 SARS patients in acute progressive stage in Guangdong
      province were all IFA positive. SARS antibody could be detected since the sixth
      day after onset, and the titer increased from 1:40 to 1:600 on the ninth day.
      CONCLUSION: Immunofluorescence assay is highly specific and sensitive in
      detection of SARS. This reagent is safe and easy to prepare.

PMID- 15949362
TI  - [Immune mechanism of cardiac remodeling induced by antibodies against to the
      alpha1-adrenergic receptor].
AB  - OBJECTIVE: To study the effects of autoantibodies against alpha1-adrenergic
      receptor on the cardiac remodeling and relevant mechanism. METHODS: Four-week-old
      male Wistar rats were immunized with synthesized second extracellular loop of
      alpha1-adrenergic receptor and raised for one year, with spontaneously
      hyperetensive rats (SHRs) and no-immunized Wistar rats of the same age as
      controls. Every one or two months blood was collected from the caudal vein to
      detect the level of serum antibodies to alpha1-adrenergic receptor by ELISA and
      the systolic blood pressure (SBP) and heart rate were measured. One year after
      the rats were killed and their hearts were taken out. The heart weight/body
      weight ratio, cardiac muscle cell cross-sectional area (CSA), interstitial
      collagen volume fraction (CVF) and the ratio of perivascular collagen area to
      vessel luminal area (PVCA) were calculated, the expression of alpha1-adrenergic
      receptor, c-fos and c-Jun in heart were measured by RT-PCR, Western blotting and
      immunohistochemistry. RESULTS: During the experiment the blood pressure of the
      SHRs were significantly higher than those of the immunization group and normal
      control group (both P < 0.01) without significant difference between the 2 latter
      groups. The heart weight/body weight ratio, CSA, CVF and PVCA of the
      immobilization group were 3.32 mg/g +/- 0.25 mg/g, 231 microm(2) +/- 11
      microm(2), 5.40% +/- 0.66% and 1.89 +/- 0.62 respectively, all significantly
      higher than those of the normal control group (3.06 mg/g +/- 0.25 mg/g, 197
      microm(2) +/- 19 microm(2), 3.22% +/- 0.15% and 0.86 +/- 0.17 respectively), but
      still significantly lower than those of the SHR group. Since the second week
      after immunization, the titre of antibody against of the immunization group began
      increase, peaked in the second and third months, and then decreased slowly, and
      remained at a high level by the end of experiment. The titre of antibody was not
      correlated with blood pressure. Hypertrophy of cardiac muscle cells and increase
      of sedimentation of collagen in stroma were seen in the hearts of the
      immunization group. RT-PCR showed that the expression of alpha1D-adrenergic
      receptor mRNA of the immunization group was 0.55 +/- 0.01, significantly lower
      than that of the normal control group (0.88 +/- 0.08, P < 0.05); the expression
      of c-jun mRNA in the immunization group was 0.82 +/- 0.02, significantly higher
      than that in the normal control group (0.42 +/- 0.07, P < 0.05); and there were
      no significant differences in the expressions of heart alpha1A- and alpha1B
      afrenergic receptors and c-fos mRNAs between these 2 groups. Western blotting
      showed that the expression of c-jun protein in the immunization group was 6.24 +/
      2.13, significantly higher than that in the normal control group (2.55 +/- 0.58,
      P < 0.05); and there were no significant differences in the expressions of c-fos
      andalpha1A-adrenergic receptor proteins between these 2 groups. CONCLUSION: The
      antibodies against alpha1-adrenergic receptor up-regulates the expression of c
      jun in cardiac muscle cells and interstitial fibroblast, which may be an
      immunologic mechanism of cardiac remodeling.

PMID- 15949363
TI  - [RNA interference inhibits replication and expression of hepatitis B virus in
      mice].
AB  - OBJECTIVE: To develop a mouse model of acute hepatitis B virus infection and to
      observe the RNA interference-mediated inhibition of HBV replication and
      expression in the mouse model. METHODS: Thirty Balb/c mice were randomly divided
      into 5 equal groups: group A to be injected with pHBV1.3, naked plasmid
      containing 1.3 time HBV ayw type whole genome eukaryotic expression vector, via
      the caudal vein as infection group; group B to be injected with pHBV1.3 and pSI
      C, plasmid expressing HBV-C specific short hairpin RNA, as interference group;
      group C to be injected with pHBV1.3 and pSI-C mut, a mutant RNAi vector, as
      mutant interference group; group D to be injected with pHBV1.3 and pGFP, siRNA
      transcription vector targeting green fluorescence protein (GFP); and group E to
      be injected with PBS as blank controls. Six days after blood was collected and
      the mice were killed and their livers were taken out. ELISA was used to measure
      the concentration of HBsAg in the serum. Immunohistochemistry and RT-PCR were
      used to detect the expression of HBcAg and HBV C mRNA in the liver. RESULTS:
      Three days after injection the HBsAg expression in the sera of the infection
      group was strongly positive. Six days after injection expression of HBsAg was
      negative in the interference group and blank control group, and was positive in
      the infection group, mutant interference group, and irrelevant group, however,
      with significantly lower OD values in the latter 2 groups compared with in the
      infection group (both P < 0.05). Six days after injection immunohistochemistry
      showed that HBcAg expression in liver was positive in the infection group, weakly
      positive in the mutant interference group and irrelevant interference group, and
      was negative in the blank control group and interference group. RT-PCR showed
      clear expression of HBV C mRNA in the infection group, mutant interference group,
      and irrelevant interference. CONCLUSION: RNAi technique specifically and
      effectively inhibits the replication and expression of HBV. siRNA has significant
      potential to become a new type antiviral drug. The establishment of an animal
      model of acute HBV infection in mice by hydrodynamic injection of naked plasmid
      has solved, to a certain degree, the problem of lack of appropriate animal model
      of HBV infection.

PMID- 15949364
TI  - [Effect of granulocyte-macrophage colony stimulating factor on the repair of
      vessel intima damaged by balloon].
AB  - OBJECTIVE: To observe the effect of granulocyte-macrophage colony stimulating
      factor (GM-CSF) on the repair of damaged iliac arteries. METHODS: Twenty-four
      male New Zealand White rabbits were randomized to two equal groups: GM-CSF group
      receiving subcutaneous injection of GM-CSF (10 microg.kg(-1).d(-1)), and control
      group receiving subcutaneous injection of normal saline. Seven days later all
      rabbits underwent insertion and expansion of balloon into the right iliac
      arteries so as to cause damage. Four weeks after the operation the operated iliac
      arteries of the GM-CSF group and the left iliac arteries of the control group
      were collected to undergo pathological examination. The repair and hyperplasia of
      intima were observed by microscopy and the indices of restenosis were evaluated
      by computerized planimetry. RESULTS: Histological examination showed that
      hyperplasia of neogenetic intima was lighter, numbers of vascular smooth muscle
      cells and fibrous tissue were less, degree of lumen stenosis was slighter, and
      the endothelium was more integrated in the GM-CSF group in comparison with the
      control group. Morphometry showed that the lumen area of the GM-CSF group was
      1.27 mm(2) +/- 0.31 mm(2), significantly larger than that of the control group
      (0.92 mm(2) +/- 0.24 mm(2), P < 0.05). The area of neogenetic intima of the GM
      CSF group was 0.85 mm(2) +/- 0.34 mm(2), significant smaller than that of the
      control group (1.18 +/- 0.38, P < 0.05), and the percentage of intimal
      hyperplasia of the GM-CSF group was 40% +/- 7%; significantly lower than that of
      the control group (55% +/- 6%, P < 0.05). CONCLUSION: GM-CSF promotes the repair
      of intima, reduces the new intima formation, and decreases the rate of
      restenosis.

PMID- 15949365
TI  - [Isolation and culture technics of human sweat glands].

PMID- 15949367
TI  - [SPARC and malignant neoplasms].

PMID- 15949368
TI  - [Cardiac hemangioma--a case report].

PMID- 15949369
TI  - [Paget disease of single bone--a case report].

PMID- 15949371
TI  - [A few ideas about study and diagnosis of osteoporosis].

PMID- 15949372
TI  - [Quality of bones].

PMID- 15949373
TI  - [Diagnosis of osteoporosis and some related issues].

PMID- 15949374
TI  - [Effects of estrogen on bone-turnover and its prevention and control of
      osteoporosis ].

PMID- 15949375
TI  - [Fracture due to osteoporosis].

PMID- 15949376
TI  - [Aging and bone quality].

PMID- 15949377
TI  - [Relationships between circulating matrix metalloproteinase-1, -2 and
      metalloproteinase-1 levels and bone biochemical markers and bone mineral density
      in Chinese postmenopausal women].
AB  - OBJECTIVE: To study the serum matrix metalloproteinase-1 (MMP-1), matrix
      metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      levels, and the correlations of MMP-1, MMP-2, and TIMP-1 with bone turn-over
      markers and bone mineral density (BMD) in aged postmenopausal Chinese women.
      METHODS: The serum MMP-1, MMP-2, TIMP-1, serum bone alkaline phosphatase (BAP),
      serum osteocalcin (OC), serum cross-linked N-telopeptides of type I collagen
      (NTX) of 297 Chinese female volunteers aged 48 - 89 were measured using ELISA.
      BMD were measured using dual energy X-ray absorptiometry in aged postmenopausal
      Chinese women. RESULTS: (1) There were no significant negative relationships
      between MMP-1, TIMP-1 and BMD and bone biochemical markers. (2) A weak negative
      relationships were found between MMP-2 and BMD. Adjusted by age and body weight,
      the correlation of MMP-2 with BMD of neck of femur and hip disappeared. (3)
      Positive correlations between MMP-2 and BAP, OC, NTX was found (all r = 0.193,
      0.231, 0.249, P < 0.01) (4) Serum MMP-2 concentrations were significantly higher
      in postmenopausal women with osteoporosis (1466 microg/L +/- 313 microg/L) than
      in age-matched normal controls (1222 microg/L +/- 243 microg/L) and osteopenia
      subjects (1282 microg/L +/- 220 microg/L). CONCLUSION: There are significant
      correlations between serum MMP-2 and bone metabolism, and MMP-2 may increase with
      increases in bone-turnover. The increases of serum MMP-2 appear possibly as a
      concomitant event in high bone turnover state, such as postmenopausal
      osteoporosis.

PMID- 15949378
TI  - [Impacts of osteoclast-like cells cultured on bone wafer and their sub-cellular
      structures on osteoblast].
AB  - OBJECTIVE: To investigate the effects of osteoclast-like cells (OLC) and its sub
      cellular structures on the osteoblast (OB) differentiation and function. METHODS:
      Spleen cells from C57 mice administrated with 5-fluorouracil were induced by IL
      3, 6 and granulocyte-macrophage colony stimulating factor (GM-CSF), and 1alpha,
      25-(OH)(2)D(3) to obtain massive OLCs. These OLC cells were cultured in culture
      fluid and on bone wafers (called bolcs). Osteoblasts were cultured and added with
      NaF, OLCs of two kinds, culture fluid free of OLC, and sub-unit structures such
      as nucleus, mitochondria, and cytoplasma from OLCs for 5 days. The proliferation
      rate of OBs was measured by MTT method and the alkaline phophatase (ALP) activity
      was measured by PNPP method. Immunochemistry was used to detect the core-binding
      factor alpha1 (Cbfalpha1) in the OBs, Enzyme linked immunosorbent assay was used
      to measure the osteocalcin. RESULTS: The OB number was lower in the OLC (1.288 +/
      0.039), OLC cytoplasm (1.138 +/- 0.024), 50% OLC culture fluid (1.203 +/-
      0.033), 50% OLC culture medium of OLCs cultured on bone wafer (1.128 +/- 0.028)
      in comparison with the pure OB group (1.393 +/- 0.016, all P < 0.05). The
      increase functions of OBs by OLC cultured on bone wafer and their nucleus and
      mitochondria were all more significant than those of the OLCs not cultured on
      bone wafer. The ALP activity was increased in the NaF (1.027 +/- 0.024), OCL
      cytoplasm (1.850 +/- 0.033), 50% OLC medium (2.074 +/- 0.065), 50% OLC medium of
      OLCs cultured on bone wafer (1.718 +/- 0.048), and mitochondria and cytoplasm of
      the OLC cultured on bone wafer groups (1.246 +/- 0.037, all P < 0.05). NaF
      (0.0825 +/- 0.0025), OLCs (0.0775 +/- 0.0025), nucleus (0.0775 +/- 0.0025),
      mitochondria (0.0875 +/- 0.0025), and cytoplasm of OLCs (0.1100 +/- 0.0007), 50%
      OLC medium (0.0900 +/- 0.0000), 50% OLC medium of OLCs cultured on bone wafer
      (0.1200 +/- 0.0041), OLCs cultured on bone wafer and nucleus, mitochondria, and
      cytoplasm of OLCs cultured on bone wafer all significantly increase the
      oeteocalcin activity of OBs (0.525 +/- 0.0063, all P < 0.05). NaF (57.6% +/-
      2.6%), OLC cytoplasm (45.3% +/- 4.7%), 50% OLC medium (46.6% +/- 3.3%), 50%
      medium of OLCs cultured on bone wafer (54.0% +/- 2.1%), OLCs cultured on bone
      wafer (44.8% +/- 3.0%), and cytoplasm of OLCs cultured on bone wafer (48.7% +/-
      3.5%) all significantly increased the Cbfalpha1 protein in the OBs (32.8% +/-
      4.5%, all P < 0.05). CONCLUSION: The sub-cellular elements of OLC and the
      supernatant of OLC culture media free of OLC promote the functions of OB,
      especially the OLCs cultured on bone wafer.

PMID- 15949379
TI  - [Effects of estradiol and progesterone on the expression of insulin receptor
      substrate in human osteoblasts].
AB  - OBJECTIVE: To investigate the effects of 17beta-estradiol (E(2)) and progesterone
      (P) on the expression of IRS in human osteoblast cells (HOBs) and further study
      the mechanism of E(2) and P on postmenopausal osteoporosis (PMOP). METHODS:
      Osteoblasts from cancellous bones of normal adults were cultured and underwent
      intervention of E(2) and P respectively. Semi-quantitative RT-PCR was used to
      measure the expression of mRNAs of IRS-1 and IRS-2. The expression of the
      proteins of IRS-1 and IRS-2 were detected by Western blotting. The expressions of
      phosphorylated IRS protein (P-IRS) was examined by immunocoprecipitation/Western
      blotting. RESULTS: The expression level of IRS-2 mRNA in the HOBs undergoing
      intervention of E(2) and P were 421% +/- 68% and 327% +/- 54% that of the control
      group respectively (P < 0.05 and P < 0.01). The expression level of IRS-2 mRNA in
      the HOBs undergoing intervention of E(2) combined with P was 496% +/- 54% that of
      the control group (P < 0.01). However, the expression level of IRS-1 was not
      significantly influenced by E(2) and/or P (all P > 0.05). The expression level of
      IRS-2 protein and phophorylated IRS-2 protein in the HOBs undergoing intervention
      of E(2), P, and E(2) combined with P were 487% +/- 65%, 507% +/- 54%, 552% +/-
      47% and 483% +/- 52%, 527% +/- 76%, and 717% +/- 86% that of the control group (P
      < 0.05, P < 0.01, and P < 0.05). The P-IRS-1 protein level of the HOBs undergoing
      intervention of E(2), P, and E(2) combined with P were 54% +/- 7.6%, 37% +/-
      4.2%, and 21.2% +/- 3.0% that of the control group (P < 0.05, P < 0.01, and P <
      0.01). CONCLUSION: E(2) and P up-regulate the expression of IRS-2 mRNA in HOBs.
      Combined intervention of E(2) and P positively creates a synergistic effect on
      the up-regulation of IRS-2 mRNA. E(2) and P have no effects on the expression of
      IRS-1 mRNA. E(2) and P increase the expression of IRS-2 protein and P-IRS-2.
      Combined intervention of E(2) and P presents a positive synergistic effect on the
      up-regulation of P-IRS-2. However, they show no effect on the expression of IRS-1
      protein, and down regulate the phosphorylation of IRS-1 protein.

PMID- 15949380
TI  - [Epidemiologic analysis of COPD in Guangdong province].
AB  - OBJECTIVE: To survey the prevalence of chronic obstructive pulmonary disease
      (COPD) in urban and rural areas in Guangdong Province and relevant risk factors.
      METHODS: Using the same protocol including Burden of Obstructive Lung Disease
      (BOLD) questionnaire, a questionnaire survey was conducted among 3449
      respondents, 1370 males and 1916 females, aged over 40 with an average age of
      56.8, by random disproportional cluster sampling in Liwang District of Guangzhou
      City and Yunyan Town, Lechang City, northern Guangdong Province. Spirometry was
      performed in all subjects. Lung function indices were regarded as gold criteria
      of diagnosis of COPD. RESULTS: There were 3286 cases with full data and good
      quality spirometry test, 1370 males and 1916 females, aged 56.8. The total
      prevalence of COPD was 9.4%. The prevalence of COPD in the males was 15.9%,
      significantly higher than that in the females (4.8%, P < 0.01). The prevalence in
      the rural area was 12.0%, significantly higher than that in the urban area (7.4%,
      chi(2) = 20.3, P < 0.01). 67.7% of the patients with COPD presented symptoms such
      as cough, expectoration and/or dyspnoea. 58.7% of the COPD patients (78.9% of the
      male patients and 10.9% of the female patients) smoked. The odd ratio (OR) for
      COPD in the smokers was 2.59 (95% CI 1.87 - 3.59). Only 15.1% of the smokers
      (17.9% of the male smokers and 4.1% of the female smokers) developed COPD. No
      significant relationship was found between pack years of cigarette smoking and
      COPD prevalence. The risk of COPD was increased when biomass fuels were used in
      house cooking (OR = 1.54 95% CI 1.08 - 2.20). Furthermore, the combination of
      biomass fuels and cigarette smoking further increased the risk with the OR of
      4.41 (95% CI 3.22 - 6.04), indicating a synergetic impact of smoking and biomass
      burning on the prevalence of COPD. The Prevalence of doctor-diagnosed COPD based
      on the clinical manifestation was significant lower than the actual prevalence
      (only 31.0%). CONCLUSIONS: COPD is a very common disease in Guangdong. The
      prevalence of COPD is higher in the rural area than in the urban area, which may
      be attributed to the synergic effect of smoking and biomass burning. Lung
      function test is of great importance in COPD diagnosis, especially in the earlier
      stage of COPD and those asymptomatic COPD patients.

PMID- 15949381
TI  - [Epidemiology of cardiovascular risk in Chinese chronic kidney disease patients].
AB  - OBJECTIVE: To identify the risk factors associated with cardiovascular disease
      (CVD) in Chinese chronic kidney disease (CKD) patients. METHODS: As part of a
      multicenter Chinese cohort study, the clinical data associated with CVD of 1239
      patients with CKD (stage 2 - 5) hospitalized in 7 grade 3A hospitals distributed
      in 5 regions of China 2002 - 2003 were collected. Logistic regression model was
      used to analyze the association between CVD and the demographic variables,
      lifestyle, medical history, medication, physical examination, and laboratory
      variables. RESULTS: (1) Increase of serum C-reactive protein (CRP, cut off > 10
      mg/L) was an independent risk factor for development of coronary artery disease
      (CAD) (OR 2.13; 95% confidence interval [CI], 1.32 - 3.43). 21.5% of the patients
      in this group showed a value of CRP > 10 mg/L. (2) Being female, anemia, and
      systolic hypertension were the major determinants of the development of left
      ventricular hypertrophy (OR 2.99, CI 2.09 - 4.26; OR 2.66, CI 1.19 - 3.57; and OR
      1.02, CI 1.00 to -1.02). 54.2% of the patients in this group had their systolic
      pressure controlled under 140mmHg, and only 15% of the patients in this group had
      their hemoglobin remain at the level >or= 110 g/L. (3) There was a significant
      interaction between the calcium-phosphate product and congestive heart failure
      (CHF) (OR 1.023, CI 1.01 - 1.03). 25.9% of the patients in this cohort had their
      calcium-phosphate product >or= 55. (4) Hypoalbuminemia (OR 6.01, CI 1.25 - 28.96)
      and diastolic hypertension (OR 1.05, CI 1.00 - 1.09) played major role in
      determining cerebrovascular accidents (CVA). In these cohort the prevalence of
      hypoalbuminemia was 37.3%. (5) Diabetes was associated with CAD (OR 2.34), CHF
      (OR 1.97), and CVA (OR 4.40), although its prevalence was lower in Chinese CKD
      patients (20%). Age was the risk factors of CAD (OR 1.04) and CVA (OR 1.22).
      Hypertension was associated with LVH (OR 1.016), CHF (OR 1.02), and CVA (OR
      1.04). CONCLUSION: CKD is associated with nontraditional risk factors for the
      development of CVD, including chronic inflammation, malnutrition and calcium
      phosphate disorders. Particular care must be taken to give optimal treatment for
      the most important CVD risk factors active in Chinese CKD patients, e.g. anemia
      and hypertension.

PMID- 15949383
TI  - [Efficacy of anti-HIV treatment and drug-resistance mutations in some parts of
      China].
AB  - OBJECTIVE: To evaluate the Virologic and Immunologic efficacy of HAART on Chinese
      HIV/AIDS patients and to assess the impact of of HAART on drug resistance
      mutations. METHODS: Three cohorts of Liaoning, Jilin and Henan province received
      three different regimens for 6 months respectively. Regimen of Liaoning cohort
      comprised Efavirenz + Indinavir (EFV + IDV), regimen of Jilin cohort comprised
      Stavudine + Didanosine + Efavirenz (d4T + ddI + EFV) and regimen of Henan cohort
      comprised Stavudine + Didanosine + Nevirapine (d4T + ddI + NVP). Viral load,
      CD4(+) T cell count and drug resistance genotype were detected on the three
      cohorts before and after treatment. Partial HIV-1 pol genes encoding protease and
      1 - 220 amino acid of reverse transcriptase were amplified by RT-PCR and then
      automatically sequenced. All sequences were compared with the data of Stanford
      HIV Drug Resistance Database to assess resistance mutations against reverse
      transcriptase inhibitors (RTIs) and protease inhibitors (PIs). RESULTS: During
      observation of 6 months, viral suppression to undetectable level and Elevated
      CD4(+)T cell count efficacy were achieved on partial Chinese HIV/AIDS patients in
      each of the three different regimens, even in some patients with rather low
      CD4(+)T cell count baseline. Before HAART, no primary mutations against PIs and
      RTIs were detected on the three cohorts, except one patient in Liaoning cohort.
      But after HAART, drug resistance mutations against RTIs occurred on each of the
      three cohorts. K103N is the most common mutation against NNRTIs, which can cause
      high-level resistance to each of the available NNRTIs. Y181C is another common
      mutation occurred in Henan cohort, which causes crossing drug resistance and
      multi-drug resistance to NNRTIs. In addition, intermediate level and low level
      resistance against NRTIs caused by K65R and L74V can also be found, but less
      commonly. CONCLUSION: Treatment naive Chinese HIV/AIDS patients were sensitive to
      HAART. Expected virologic and immunologic efficacy of HAART were achieved on
      Chinese HIV/AIDS patients, but after the introduce of HAART, the high prevalence
      of drug resistance mutations against NNRTIs and NRTIs, crossing drug resistance
      and multi-drug resistance reminded us to pay more attention to the drug
      resistance mutations detection, treatment standardization, and to avoid drugs
      wasting and prevent the prevalence of drug resistance strains.

PMID- 15949384
TI  - [Comparison of vocalization development between normal and congenitally hearing
      impaired infants during pre-language period].
AB  - OBJECTIVE: To compare the characteristics of vocalization and relevant perceptual
      characteristics between normal hearing infants and congenitally hearing impaired
      infants during pre-language period. METHODS: Speech spectrograms were analyzed,
      and the presentation time and frequency of pre-canonical babbling, canonical
      babbling, pointing behaviors and meaningful words were compared and statistically
      analyzed among 18 normal hearing infants, 11 profoundly congenitally hearing
      impaired infants that were divided into 2 groups: group A of deaf infants (n =
      11) to be aided before 8 months of age and group B of deaf infant (n = 17) to be
      aided after 8 months of age. RESULTS: There was no significant difference in the
      presentation time and frequency of pre-canonical babbling among the 3 groups.
      Canonical babbling, pointing behaviors and meaningful words occurred the earliest
      and with the highest frequency in the normal hearing group, followed by the group
      A of deaf infants and group B of deaf infants in succession. CONCLUSION: Pre
      canonical babbling appears in profoundly hearing impaired infants, suggesting
      that it is a kind of phonation activity free of hearing feedback. Better language
      development can be achieved when early intervention is carried out for
      congenitally hearing impaired infants within 8 months of age.

PMID- 15949385
TI  - [Feasibility of breast conservation surgery after neoadjuvant chemotherapy for
      breast cancer].
AB  - OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the
      feasibility of conservative breast surgery after reducing the size of a primary
      tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients
      with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60
      mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour
      continuous infusion on day 2 with 21 days as a cycle from July 2001 to April
      2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or
      modified mastectomy was performed after the tumor was reduced to less than 3 cm
      in diameter. The nonresponders received modified mastectomy. RESULTS: The overall
      response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen
      patients (50%) obtained clinical complete response (cCR), including 7 cases (23%)
      with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical
      partial response (cPR), and 2 (7%) no change (NC). No case showed progression of
      disease. Twenty-six (87%) cases were downstaged according to the TNM system
      classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and
      was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation.
      Eighteen (60%) of them were candidates for breast conserving therapy, and
      actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment
      for operable breast cancer, NCT with epirubicin plus paclitaxel results in
      significant downstaging or eliminating of primary tumors in breast cancer, thus
      expanding the indication of breast conservation therapy.

PMID- 15949386
TI  - [Ultrasonographic assessment of urethral condyloma acuminatum in men].
AB  - OBJECTIVE: To evaluate the value of ultrasonography in diagnosing urethral
      condyloma acuminatum (CA) in men. METHODS: Twenty-two male patients, aged 36 +/-
      19, diagnosed as with urethral CA based on history and clinical symptoms
      underwent ultrasonography and urethroscopy. The patients were asked to micturate
      to distend the urethra. The posterior urethra was detected by transrectum
      approach. Transperineal scans were performed to image the bulbar urethra, scrotal
      urethra and penile urethra. The sonographically positive results were compared
      with the pathological results. RESULTS: Eighty-three vegetations were found in
      the anterior urethra of seventeen patients, and eighty-one vegetations were
      diagnosed as CA by pathology, of which 1.2% were polyp shape, 38.3% papillary
      shape, and 60.5% cauliflower mass. Sonourethrography was an accurate predictor of
      papillary shape and cauliflower mass; however, it was difficult to differentiate
      between polyp shape vegetation and crystal. CONCLUSION: Sonourethrography is a
      sensitive and accurate tool not only for primary diagnosis of but also for follow
      up of urethral CA in men.

PMID- 15949387
TI  - [Inhibition effects of par-4 antisense oligodeoxynucleotide on apoptosis of PC12
      cell induced by glutamate is mediated by ERK1/2].
AB  - OBJECTIVE: To investigate the inhibition effects of par-4 antisense
      oligodeoxynucleotide on apoptosis of PC12 cell induced by glutamate and its
      signal transduction mechanism. METHODS: (1) Cationic lipid-mediated par-4
      antisense oligodeoxynucleotide (Par-4-AS-ODN) was transfected into PC12 cells
      before they were treated with glutamate. Mismatch oligodeoxynucleotide (MS-ODN)
      were also transfected into cells as controls. (2) Morphological observation and
      the detection of anti-apoptosis effects of par-4-AS-ODN on PC12 cells were done
      with the Laser Scanning confocal Microscope by double staining the cells with
      acridine orange/ethidium bromide (AO/EB), addition to with flow cytometry. (3)
      Western blot was used to detect the protein levels of par-4 and phosphorylated
      ERK(1/2) at threonine-202 and Tyrosine-204. RESULTS: (1) Par-4-AS-ODN
      significantly suppressed up-regulation of the par-4 protein levels induced by
      glutamate in PC12 cells. (2) Par-4-AS-ODN could resist the decrease of
      phosphorylated ERK(1/2) (Thr202/Tyr204) induced by glutamate in PC12 cells. (3)
      Par-4 AS-ODN could inhibit apoptosis of PC12 cells induced by glutamate. But its
      inhibition effect could be eliminated by PD98059, a selective MEK(1) inhibitor
      which could inhibit phosphorylation of ERK(1/2). CONCLUSION: Par-4 AS-ODN may
      inhibit apoptosis of PC12 cells induced by glutamate, and its inhibition effects
      may be medicated by the activation of ERK(1/2).

PMID- 15949388
TI  - [Study of serum proteome biomarkers with relation to the formation of portal vein
      tumor thrombi in hepatocellular carcinoma patients].
AB  - OBJECTIVE: To screen serum proteome biomarkers and establish predictive model
      with relation to the formation of portal vein tumor thrombi (PVTT) in
      hepatocellular carcinoma (HCC) patients. METHODS: Serum samples were collected
      from 135 HCC patients, which were divided, into training set (including 33 HCC
      patients with PVTT and 62 HCC patients without PVTT) and blind testing set
      (including 18 HCC patients with PVTT and 22 HCC patients without PVTT). Special
      serum protein or peptide pattern was determined by SELDI-TOF-MS measurement after
      treating the sample onto WCX2 protein chip for each case. The obtained data were
      analyzed by BioMarker Wizard software to screen serum proteome biomarkers with
      relation to the formation of PVTT, while decision tree classification algorithm
      and blind validation were determined by Biomarker Patterns Software. RESULTS:
      Ranging from 1100 to 30 000 at the m/z value, 100 protein features were detected
      in the serum protein pattern stably. Among them, 6 protein peaks with the m/z
      value of 3478, 1314, 1744, 1725, 2022 and 3380 were upregulated, 10 proteins
      peaks with the m/z value of 8901, 9353, 9415, 8773, 2766, 2745, 8697, 7773, 8569
      and 1373 were downregulated respectively in the group of HCC with PVTT. The 7
      candidate protein peaks with the m/z value of 3478, 2022, 8901, 9415, 8773, 2766
      and 2745 were selected to establish predictive model by BPS with a sensitivity of
      75.8% (25/33) and specificity of 82.3% (51/62). An accuracy of 87.5% (35/40),
      sensitivity of 100% (18/18), specificity of 77.3% (17/22), positive predictive
      value of 78.3% (18/23), and negative predictive value of 100% (17/17) were
      validated in blind testing set. CONCLUSION: Sixteen candidate proteome biomarkers
      may be related with the formation of PVTT in HCC patients. Decision tree
      classification algorithm may have great clinical significance in predicting the
      formation of PVTT.

PMID- 15949389
TI  - [Effects of preoperative transcatheter artery chemoembolization on survival rate
      of hepatoma with percutaneous radiofrequency ablation].

PMID- 15949390
TI  - [Study on the cytotoxic T-lymphocyte related antigen 4 exons 1A/G49 polymorphism
      in patients of insulin-dependent diabetes mellitus and their parents].

PMID- 15949391
TI  - [Uses of Enclose in coronary bypass in non-cardiopulmonary bypass surgery].

PMID- 15949392
TI  - [More research work should be done on the pathogenesis of autoimmune injuries to
      the multiple organs in some T2 diabetes mellitus].

PMID- 15949393
TI  - [Immediate cardioversion of atrial fibrillation and atrial flutter lasting less
      than 90 days by ibutilide versus propafenone: a multicenter study].
AB  - OBJECTIVE: To compare the efficacy and safety of ibutilide versus propafenone in
      immediate cardioversion of atrial fibrillation (AF) and atrial flutter (AFL)
      lasted less than 90 days. METHODS: 212 consecutive patients suffering from AF or
      AFL all lasting less than 90 days that were diagnosed and treated in 5 medical
      centers were randomly assigned into two groups: ibutilide group (n = 107,
      including 75 AF cases and 32 AFL cases, receiving intravenous injection of
      ibutilide 1mg over 10 minutes) and propafenone group as control group (n = 105,
      including 76 AF cases and 29 AFL cases, receiving intravenous injection of
      propafenone 70 mg over 10 minutes). If AF/AFL still persisted 10 minutes after
      treatment, the above dose was repeated. The conversion rate within 1.5 hours and
      adverse effects within 4 hours were observed. RESULTS: (1) The conversion rate on
      AFL of the ibutilide group was 78.1%, significantly higher than that of the
      propafenone group (48.3%, P < 0.01), while no significant difference was observed
      in the conversion rate on AF (54.7% vs. 39.5%, P > 0.05) and the mean conversion
      time (P > 0.05). However the overall conversion rate on AFL and AF of the
      ibutilide group was 61.7%, significantly higher than that of the propafenone
      group (41.9%, P < 0.05). (2) The conversion rate on AF/AFL lasting less than 48 h
      was 65.9% in the ibutilide group, not significantly different from that of the
      propafenone group (55.7%), the conversion rate on AF/AFL lasting 3 approximately
      30 d in the ibutilide group was 66.7%, significantly higher than that of the
      propafenone group (26.3%, P < 0.05), and the conversion rate on AF/AFL lasting 31
      - 88 d was 50%, significantly higher than that of the propafenone group (0, P <
      0.01). (3) There was no difference in the times needed for conversion between
      these 2 groups. (4) The most severe adverse effect in the ibutilide group was
      short run of ventricular tachycardia occurring in 5 cases among which 4 cases
      recovered simultaneously and one case recovered after accepting a bolus dose of
      100 mg lidocaine. The most severe adverse effects in propafenone group were RR
      interval longer than 1.5 s (4 cases) and transient hypotension. An acute coronary
      event was also seen in propafenone group, however, unrelated to the experimental
      drug. CONCLUSION: Intravenous administration of ibutilide in cardioversion of AF
      and AFL is safe and effective.

PMID- 15949394
TI  - [Epidemiological study of Helicobacter pylori infection and its risk factors in
      Shanghai].
AB  - OBJECTIVE: To explore the Helicobacter pylori (Hp) infection status in Shanghai
      and its risk factors. METHODS: A questionnaire survey including 60 items related
      to Hp was conducted among 1925 persons, 976 males (50.7%) and 949 females
      (49.3%), aged 37 +/- 11 (15 approximately 72), selected by cluster sampling in 12
      rural and urban areas in Shanghai. Peripheral blood was collected to detect Hp
      IgG antibody so as to evaluate the past infection status and (14)C urea breath
      test (UBT) was performed so as to evaluate the present infection status. Fecal Hp
      antigen test was done in the subjects under 18 years of age. RESULTS: 1822 of the
      1925 subjects (94.6%) underwent the 3 tests. were followed antibody detection and
      (14)C UBT and response with questionnaires. The Hp infection rate was 66.4% in
      general, and 68.4% in the females, somehow higher than in the males (64.3%, P =
      0.067). The infection rate was different in different age groups, was the lowest
      in the age group of 15 approximately 19 (44.4%) and the highest 70% in age group
      of 20 approximately 30 (70%), then somewhat lower and gradually became higher.
      Socio-economic status was related to Hp infection. Hp infection was related with
      such factors as eating raw vegetables and fruits, and never washing raw
      vegetables and fruits before eating. The knowledge rate about Hp infection was
      only 33.2% among the respondents. Only 23.8% of the respondents knew well the
      transmission route of Hp. CONCLUSION: Hp infection rate is rather high in
      Shanghai. Hp infection is related to socio-economic status, and family dietary
      and sanitary habits.

PMID- 15949395
TI  - [The operation treatment for severe and rigid idiopathic scoliosis].
AB  - OBJECTIVE: To discuss the operation treatment for the severe and rigid idiopathic
      scoliosis. METHODS: The clinical data of 24 patients with severe and rigid
      idiopathic scoliosis, 15 females and 9 males, with an average age of 17 (12
      approximately 20) who had undergone operations from June 1999 to June 2003 were
      analyzed retrospectively. The patients were classified according to PUMC
      operative classification systerm, including 16 cases of type Ia, 2 cases of type
      Ib, 3 cases of type IIb2, and 1 case of types IIb1, IIc2, and IIc3 each. The
      average standing coronal Cobb angle was 98 degrees (80 degrees to 117 degrees )
      and the average flexibility rate of the major curves was 20.8% (5% to 29.5%)
      before operation. Fifteen cases had sagittal deformities. Bone fusion was
      performed on all the cases according to the PUMC classification principles. 17
      cases received anterior spinal release with posterior correction by two stages,
      and 2 cases by one stage. 5 cases received one-stage posterior correction. All
      the patients were followed up for 12 approximately 30 months (18 months on
      average). RESULTS: The mean standing coronal Cobb angle of the major curves was
      reduced to 58 degrees (32 degrees to 100 degrees ) after operation with a
      correction rate of 41.0% (10.9% to 61.0%). The results of sagittal plane
      correction were satisfying. The mean Cobb angle of the major curves at the final
      follow up was 63 degrees (31 degrees to 104 degrees ), and the mean lost was 5
      degrees (0 degrees to 10 degrees ). One case had to undergo revision surgery
      because of hook displacement. One case had steel wire broken but without
      neurological symptoms and only needed observation. No pseudoarthrosis and
      decompensation occurred. CONCLUSION: Compared with vertebral osteotomy for the
      correction of scoliosis, the anterior spinal release combined with posterior
      correction and simple posterior correction have the advantages of low risk, less
      blood loss, and low infection rate. They can be used effectively and safely for
      the correction of idiopathic severe and rigid idiopathic scoliosis. The key
      points for the surgical procedures are appropriate correction and recovery of the
      balances of the coronal and sagittal planes.

PMID- 15949396
TI  - [Successful preimplantation genetic diagnosis for beta-thalassemia using
      multiplex nested polymerase chain reaction].
AB  - OBJECTIVE: To develop single-cell multiplex nested polymerase chain reaction
      (PCR) assays for preimplantation genetic diagnosis (PGD) in couples at risk of
      having child with beta-thalassemia. METHODS: Primers were designed and
      synthesized according to the documented mutation sites common among Chinese.
      Venous blood was collected from 4 pairs of husband and wife, all heterozygotes
      for beta-thalassemia, and underwent multiple nested PCR. Intraooplasmic sperm
      injection and mechanical bio psy was used to obtain single blastomere. Multiplex
      nested PCR was used to detect the CD41-42 mutation and the closely linked
      polymorphic marker, HumTHO1 gene or CD41-42, CD41-28, IVSII654 mutation and
      HumTHO1 gene in the single blastomeres from four clinical PGD cycles. The normal
      embryos with high scores capable of continuing to divide were transplanted into
      the uteri. The process of gestation was observed. RESULTS: 200 lymphocytes were
      amplified by nested PCR. The average amplification rate of the most common 16
      beta-thalassemia mutations in Chinese population was 91.3% and the average rate
      of allele drop out for different sites was 17.0% without differences between any
      2 sites. During the 4 PGD cycles 33 embryos underwent bioassay with a success
      rate of 100%. 33 blastomeres were obtained to undergo PCR, of which 30 were
      successfully amplified with an amplification rate of 90.9%. Explicit diagnosis
      was obtained in 26 of the 30 embryos: 7 normal homozygotes, 11 heterozygotes, and
      8 abnormal or complex heterozygotes. One or more embryos were transferred back
      into the uteri of the 4 women and clinical pregnancy occurred in one woman. Five
      weeks after the implantation B-mode ultrasonography showed monocyesis, and in the
      17th week of gestational period paracentesis of cord blood showed normal
      homozygote. At last a normal female infant confirming the PGD result had been
      born, which was the first reported unaffected pregnancy resulting from PGD using
      multiplex nested PCR for couples as beta-thalassemia gene carriers. The results
      of diagnosis for embryo all corresponded to those for blastomere. The average ADO
      rate of blastomere was 13.3% (4/30). CONCLUSION: PGD using multiplex nested PCR,
      as an alternative to prenatal diagnosis, is a reliable and effective way to help
      couples-carriers of pathogenetic genes to get a healthy baby.

PMID- 15949397
TI  - [Blood vessel tissue engineering: seeding vascular smooth muscle cells and
      endothelial cells sequentially on biodegradable scaffold in vitro].
AB  - OBJECTIVE: To evaluate the effect of seeding vascular smooth muscle cells and
      endothelial cells sequentially on biodegradable scaffold in vitro. METHODS:
      Venous endothelial cells and smooth muscle cells of artery were isolated from the
      umbilical cord of newborn and cultured in vitro. The cultured arterial smooth
      muscle cells and cultured endothelial cells were seeded on the polyglycolic acid
      and polylactide (PLGA) nonwoven mesh as tissue scaffolds respectively (group A
      and group B). And cultured endothelial cells were seeded on the scaffold already
      seeded with smooth muscle cells sequentially to construct vascular patch (group
      C). One month after cultivation the patches of the 3 groups underwent HE staining
      and microscopic examination and scanning electron microscopy.
      Immunohistochemistry was used to examine the existence of actin and factor VIII
      related antigen, secreted by endothelial cells, in the cells. The levels of
      endothelin and 6-Keto-PGF1alpha in the culture solution were examined by means of
      radioimmunology so as to measure the endothelial function. Pure culture solution
      was used as blank control (group D). RESULTS: Microscopy showed that cells were
      fused into patch in the group C. HE staining showed that the smooth muscle cells
      were embedded into the PLGA scaffold and grew in multiple layers covered by a
      layer of endothelial cells on the surface. The types of cells could be identified
      by immunohistochemical procedure. The levels of endothelin and 6-Keto-PGF1alpha
      in the culture solution were 229 pg/ml +/- 34 pg/ml and 402 pg/ml +/- 108 pg/ml
      respectively in the group C, and 200 pg/ml +/- 31 pg/ml and 336 pg/ml +/- 121
      pg/ml in the group B, both significantly higher than those in the groups A and D
      (blank control group, all P < 0.05 or P < 0.05). CONCLUSION: Tissue engineering
      blood vessel with normal morphological and functional characters to a certain
      degree can be constructed through seeding cultured vascular smooth muscle cells
      and endothelial cells sequentially on PLGA scaffold.

PMID- 15949398
TI  - [Induction of uridine 5'-diphosphate-glucuronosyltransferase gene expression by
      sulforaphane and its mechanism: experimental study in human colon cancel cells].
AB  - OBJECTIVE: To study the induction of expression of uridine 5'-diphosphate (UDP)
      glucuronosyltransferase (UGT) 1A in colon cancer cells by sulforaphane (SFN) and
      its possible mechanism. METHODS: Human colon cancer cells of the line Caco-2 were
      cultured and added with SFN of different terminal concentrations, all below the
      concentration of IC(50). RT-PCR was used to examine the expression of UGT1A mRNA
      induced by SFN. Western blotting was used to detect the expression of UGT1A
      protein. The glucuronidation rate of N-hydroxy-PhIP was measured by high
      performance liquid chromatography (HPLC). The nuclear localization of
      transcription factor Nrf2 was observed by confocal laser microscopy. RESULTS: (1)
      Expression of UGT1A mRNA was observed in the Cac0-2 cells induced by SFN of the
      concentrations of 10 micromol/L approximately 35 micromol/L in a dose-independent
      manner (P < 0.05). Sulforaphane of the concentration of 25 micromol/L induced the
      UGT1A mRNA expression time-dependently. The levels of UGT1A1, UGT1A8, and UGT1A10
      mRNA expression were significantly increased in the cells treated with 25
      micromol/L sulforaphane compared to that in the controls (P = 0.006, P = 0.017,
      and P = 0.008 respectively). (2) The UGT1A protein band intensity increased
      significantly in the Coco-2 cells treated with sulforaphane of the concentrations
      10 micromol/L approximately 30 micromol/L for 24 h in comparison with the control
      cells. (3) When the microsomes from the untreated Caco-2 cells were incubated
      with N-hydroxy-PhIP there was a minor HPLC peak at the expected retention time
      for N-hydroxy-PhIP-N2-glucuronide. This peak was dramatically increased in the
      sulforaphane-treated cells, suggesting higher activities of glucuronidation of N
      hydroxy-PhIP. (4) Cytoplasmic labeling of NF-E2-related factor 2 (Nrf2), a
      transcription factor, with no nuclear staining was observed in the non-stimulated
      cells, whereas an intense nuclear labeling was observed in the sulforaphane
      treated cells, indicating the induction of nuclear translocation of Nrf2 by
      sulforaphane. CONCLUSION: (1) Low dose sulforaphane induces the expression of
      UGT1A, UGT1A1, UGT1A A8, and UGT1A A10 mRNA significantly. These changes are
      accompanied by an increase in UGT1A1 protein and increase in heterocyclic
      aromatic amine glucuronidation. (2) The induction of the phase II enzyme activity
      by SFN occurs at the transcriptional level and is regulated by Nrf2.

PMID- 15949399
TI  - [Biological impact of the COOH-terminal 40 amino acid deletions of hepatitis B
      virus X protein in hepatocellular carcinoma cells].
AB  - OBJECTIVE: To investigate the biological impact of the wild type hepatitis B
      virus X protein (HBx) and HBx3'-40, an engineered deletion mutant of HBx lacking
      the last 40 C-terminal amino acids and a transcriptional transactivator on
      hepatoma cells. METHODS: Human hepatocellular cells of the lines Huh7 and SMMC
      7721 were transfected with HBx3'-40 or HBx constructs. The integration of the
      plasmid DNA and the expression of HBx3'-40 and HBx were confirmed by Neo gene PCR
      and Western blotting respectively. The growth curves of different cells were
      obtained by MTT method. Plate clone formation test to calculate the clone
      formation rate. Flow cytometry (FCM), and Chloramphenicol acetyl transferase
      (CAT)-ELISA. Male BALB/c mice were divided into 3 groups to be inoculated
      subcutaneously with plasmids pcDNA3HBx, pcDNA3HBx3'-40, and blank plasmas pcDNA3
      as controls. The mice were killed 15 and 30 days after and the tumors were taken
      out to undergo measurement and immunohistochemistry. RESULTS: Growth curve showed
      that after transfection the HBx3'-40 group cells grew faster than HBx and pcDNA3
      transfected group cells. FCM analysis showed that HBx3'-40 transfection enhanced
      the progression of G(1) --> S phase in Huh7 cell cycle and HBx did not show such
      impact. The clone formation rates of pcDNA3HBx3'-40 group was 12.2% +/- 1.4%,
      significantly higher than those of the pcDNA3HBx, blank vector, and control
      groups (6.3% +/- 0.7%, 4.1% +/- 0.9%, and 6.1% +/- 1.1% respectively, all P <
      0.05) in the Huh7 cells. The situation was the similar in the SMMC-7721 cells:
      83% +/- 6% vs.49% +/- 8%, 27% +/- 3%, and 51% +/- 5% respectively (all P < 0.05).
      The apoptotic rates of SMMC-7721 cells under no serum condition transfected with
      HBx and HBx3'-40, especially the former, were 12.57% and 9.15%, significantly
      higher than that of the pcDNA3HBx group. The CAT expression of the pcDNA3HBx
      transfected SMMC-7721 cells was 2.913 and 3.652 times those of the pcDNA3HBx3'-40
      group and pcDNA3 group. The tumor weights of the mice inoculated with pcDNA3HBx3'
      40, pcDNA3HBx, and blank vector-transfected Huh7 cells were 1.2 g +/- 0.17 g,
      0.55 g +/- 0.12 g, and 0.48 g +/- 0.15 g respectively. The tumor weights of the
      mice inoculated with pcDNA3HBx3'-40, pcDNA3HBx, and blank vector-transfected SMMC
      7721 cells showed similar features. CONCLUSION: HBx3'-40 protein significantly
      promote the proliferation of hepatocellular carcinoma cells and is involved in
      cell apoptosis and invasion, thus supporting the hypothesis that HBx mutants play
      a key role in hepatocarcinogenesis by modifying the biological functions of HBx.
      Besides, C-terminal mutants of HBx makes p53 tumor suppressor gene lose its
      cancerostatic function.

PMID- 15949400
TI  - [Significance of ultrasound bone measurement in diagnosis of hyperthyroidism].
AB  - OBJECTIVE: To evaluate the role of ultrasound in bone density measurement in
      patients with hyperthyroidism. METHODS: The speed of sound (SOS) through distal
      radius and midshaft tibia of 118 patients with hyperthyroidism 138 males and 80
      females, aged 20 approximately 73, were measured with ultrasonic apparatus, the
      bone mass density (BMD) was measured at the lumbar spine and proximal femur with
      dual energy X-ray absorptiometry, the serum levels of total thyroxine (TT(4)),
      total triiodothyronine (TT(3)), free thyroxine (FT(4)), free triiodothyronine
      (FT(3)), and thyroid stimulating hormone (TSH) were measured by radioimmunoassay,
      and alkaline phosphatase (ALP) was measured by routine method. RESULTS: The SOS
      of the patients with hyperthyroidism was significantly lower than that of the
      healthy subjects (P < 0.05). A strong positive correlation was found between SOS
      and BMD. The prevalence of SOS (Z < -1, Z < -2.5) through distal radius and
      midshaft tibia was significantly higher than that of BMD (Z < -1, Z < -2.5) at
      lumbar spine and proximal femur in the patients with hyperthyroidism. A negative
      linear correlation was found between SOS and ALP. CONCLUSION: SOS may be one of
      the significant markers for abnormal bone metabolism for hyperthyroidism.

PMID- 15949402
TI  - [The expression of hepatocyte growth factor and its receptor in brain
      astrocytomas].
AB  - OBJECTIVE: To investigate the expression of hepatocyte growth factor (HGF) mRNA
      and its receptor (c-Met) mRNA in brain astrocytomas and their relationships with
      tumor proliferation, angiogenesis, clinical pathology and prognosis. METHODS: The
      expression of HGF mRNA, c-Met mRNA in the resected tumor tissues of 76 patients
      with brain astrocytomas, 43 males and 33 females, aged 20 - 71, were detected by
      in situ hybridization. Immunohistochemistry technique was used to test the
      expression of proliferating cell nuclear antigen (PCNA) protein and the
      microvessel density (MVD) was determined by immunohistochemistry with monoclonal
      antibody against CD34. RESULTS: The positive rates of expression of HGF, c-Met
      and PCNA in low pathologic grades of brain astrocytoma were 34.5%, 44.8% and 15%
      +/- 9% respectively, and in high pathologic grades of brain astrocytoma were
      34.5%, 44.8% and 48% +/- 12% respectively (P < 0.05). MVD in low and high
      pathologic grades of brain astrocytoma were 17 +/- 7 and 31 +/- 13 respectively
      (P < 0.05). The expression of HGF, c-Met, PCNA and CD34 was not related to sex,
      age, position of tumor and diameter of tumor. The expression of c-Met was related
      to the expression of HGF, PCNA and the MVD in the tumor tissues of these
      patients. The pathological grade, position of tumor, HGF, c-Met, PCNA, MVD had a
      significant influence on the survival time. CONCLUSION: HGF/c-Met plays an
      important role in the formation and progression of the brain astrocytoma and can
      promote tumor proliferation and intratumoral microvascular formation, and is
      closely related to the prognosis of the patients.

PMID- 15949403
TI  - [The role of KiSS-1 and matrix metalloproteinase-9 in regulation of invasion of
      trophoblasts].
AB  - OBJECTIVE: To explore the role of metastasis-related gene KiSS-1 and matrix
      metalloproteinase (MMP)-9 in regulation of invasion of trophoblasts. METHODS: RT
      PCR and Western blotting were used to detect the MMP-9 and KiSS-1 expression
      levels in the placental tissues obtained from 90 cases of normal pregnant women
      undergoing artificial abortion, induction of labor with water bag or selective
      cesarean section among which 30 cases were in the first trimester, 30 in second
      trimester and 30 cases of term pregnancy, and in the placental tissues of 40
      cases of preeclampsia (15 cases of mild and 25 cases of severe preeclampsia)
      undergoing cesarean section, and tissues of 90 cases of hydatidiform mole, 9
      cases of invasive mole and 8 cases of choriocarcinoma, all undergoing surgery.
      RESULTS: The expression levels of MMP-9 mRNA and protein were higher in first
      trimester [A value 0.391 +/- 0.215, (36 +/- 7) microg/100 microg total protein]
      and then decreased gradually with the progress of gestation. The expression
      levels of MMP-9mRNA and protein in the term placental samples were significantly
      lower than those of first-trimester (both P < 0.01). The expression levels of
      KiSS-1mRNA and metastin in normal placenta increased along with the progress of
      gestation (both P < 0.01). The KISS-1 mRNA expression level and MMP-9 protein
      expression level in the placental tissue of preeclampsia were 0.09 +/- 0.06 (A
      value) and (9.6 +/- 4.3) microg/100 microg total protein respectively, both
      significantly lower than those of the term placenta (both P < 0.01). The
      expression levels of MMP-9 mRNA and protein in the tissues of gestational
      trophoblastic disease were significantly higher than those in the first-trimester
      placenta (both P < 0.01). The expression level of KISS-1 mRNA and metastin in the
      tissues of hyddatidiform mole and invasive mole were both significantly lower
      than those in the first trimester placenta (P < 0.05, P < 0.01). The expression
      of KiSS-1mRNA and metastin in the tissues of choriocarcinoma could not be
      detected. CONCLUSION: The expression of the invasion-related gene, MMP-9, is
      positively related with, while the invasion suppressor gene, KiSS-1, is
      negatively related with the invasive ability of trophoblasts. The interaction of
      these two genes plays an important role in regulation of the invasion of
      trophoblasts.

PMID- 15949404
TI  - [Effects of prolonged selenium and iodine deficiency on monamine
      neurotransmitters in the different brain area in developing rats].

PMID- 15949405
TI  - [Influence of activation of human glioma cell CXCR4 receptor on the expression of
      vascular endothelial growth factor].

PMID- 15949406
TI  - [Hereditary spinocerebellar ataxia--a family pedigree with SCA3 gene mutation].

PMID- 15949407
TI  - [Experimental study on vascular endothelial growth factor gene stents in the
      prevention of post balloon dilatation restenosis].

PMID- 15949408
TI  - [Effects of excitation of cholinergic nerves of rat brain stem reticular
      formation on nociceptor signal transmission].

PMID- 15949409
TI  - [Human cytomegalovirus infection induced immunoglobulin A nephropathy--a case
      report].

PMID- 15949411
TI  - [Migraine and ion channels].

PMID- 15949412
TI  - [A novel small molecule cyclin-dependent kinase inhibitor flavopiridol in cancer
      therapy].

PMID- 15949413
TI  - [Current status of epirubicin in the treatment of breast neoplasm].

PMID- 15949414
TI  - [Spectrum of gene expression of a multi-drug resistant leukemia cell line with
      high tumorigenicity in nude mice].
AB  - OBJECTIVE: To investigate the mechanism of multi-drug resistance of K562-n/VCR
      cell line with both bcr-abl and mdr-1 expressions by clustering analysis of
      differential gene expression profiles. METHODS: By DNA microarray technique,
      genes differentially expressed by K562-n/VCR and K562-n cell lines were
      identified and analyzed. RESULTS: DNA microarray analysis of K562-n/VCR and K562
      n cells was repeated three times and revealed 58 genes significantly
      differentially expressed among 12,800 genes arrayed. All but one was up-regulated
      in K562-n/VCR cells. The only gene down-regulated was a-myb. The up-regulated
      genes were MDR-associated genes, oncogenes, cytoskeleton, protein kinases and
      phosphatases, apoptotic and antiapoptotic factors, metabolism, transcriptional
      regulators associated with stress response, cell cycle checkpoint control, and
      genes for signal transduction proteins. CONCLUSION: These results indicate that,
      besides MDR-associated genes, other known and unknown genes may also be involved
      in the mechanism of multi-drug resistance.

PMID- 15949415
TI  - [The function of ERK on Fas-mediated apoptotic signaling pathway of human gastric
      carcinoma cells].
AB  - OBJECTIVE: To analyze the expression and functions of ERK (extracellular
      regulated kinase) in Fas-mediated apoptosis in gastric carcinoma cell line SGC
      7901 and to elucidate the potential significance of this signaling pathway in
      tumor progression. METHODS: Radioisotope labeling and Western blotting with
      special anti-ERK antibody were used to check ERK activity in SGC-7901 cell line
      after anti-Fas antibody treatment. Apoptosis induced by several treatment factors
      was evaluated by FACS can flow cytometer. RESULTS: ERK activity increased and
      reached the peak at 30 min after treatment with anti-Fas antibody and decreased
      in PD98059 pretreated group. The number of sub-G(1) cell was 30.5% +/- 2.6% in
      PD98059 pretreated group, which was higher than anti-Fas treatment group and
      control group, respectively. CONCLUSION: In gastric cancer cell line SGC-7901,
      Fas-induced ERK activation may suppress Fas-mediated apoptosis. Inhibition of ERK
      may enhance the sensitivity of SGC-7901 cells to Fas-mediated apoptosis. Fas
      induced ERK activation may confer gastric cancer cells ability to escape the
      immune surveillance.

PMID- 15949416
TI  - [Cross-talk between c-Jun/Ets1 involved in EB virus-encoded latent membrane
      protein 1 regulates expression of matrix metalloproteinase-9 in nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To investigate effect of AP-1 and Ets binding site adjacent to matrix
      metalloproteinase-9 (MMP-9) promoter on activation of MMP-9 transcription of
      nasopharyngeal carcinoma cells transfected with EBV-encoded latent membrane
      protein 1 (LMP1), and to ascertain if cross-talk between c-Jun and Ets1 is
      involved in LMP1-regulating expression of MMP-9. METHODS: Site-directed
      mutagenesis technique was used to establish a series of mutants, including MMP-9
      CAT-Ets(-540)mt, MMP-9-CAT-AP-1(-533)mt and MMP-9-CAT-AP-1(-533)/Ets(-540)mt.
      After the mutants were transfected into LMP1-expressing NPC HNE2 cells regulated
      by Tet-on system (pTet-on-LMP1 HNE2), CAT activity of these mutants were assayed
      with induction of LMP1. With blockade of c-Jun or Ets1 antisense
      oligonucleotides, the activity of MMP-9 induced by LMP1 was assayed with gelatin
      zymography. RESULTS: The CAT activity of MMP-9-Ets(-540)mt-CAT, MMP-9-AP-1(
      533)mt-CAT, MMP-9-AP-1(-533)/Ets(-540) mt-CAT decreased significantly compared to
      MMP-9-CAT wt. After blockade with c-Jun or Ets1 antisense oligonucleotides,
      activity of MMP-9 induced by LMP1 decreased significantly, especially with
      combined blockade of c-Jun and Ets1. CONCLUSION: The results suggest that
      transcription factor AP-1 and Ets play an crucial role in activation of MMP-9
      transcription induced by LMP1, and cross-talk between c-Jun/Ets1 is involved in
      expression of MMP-9 mediated by LMP1.

PMID- 15949417
TI  - [Effect of monoclonal antibody against extracellular domain III of vascular
      endothelial growth factor receptor KDR on proliferation of vascular endothelial
      cells].
AB  - OBJECTIVE: To prepare a neutralizing monoclonal antibody (McAb) against vascular
      endothelial growth factor receptor KDR and study its biological activity.
      METHODS: Extracellular immunoglobulin (Ig)-like domain III of KDR (KDR III) was
      expressed in E. coli and purified by affinity chromatograph. Monoclonal antibody
      against KDR III was prepared by hybridoma technique. ELISA and FACS analysis were
      used to identify its specificity. Immunoprecipitation and [(3)H]-TdR
      incorporation assay were also used to detect the activity of anti-KDR McAb
      blocking the phosphorylation of KDR tyrosine kinase receptor and the influence on
      VEGF-induced mitogenesis of human endothelial cells. RESULTS: McAb Ycom1D3
      against KDR III was prepared which bound specifically to both the soluble KDR III
      and the cell-surface expressed KDR. It effectively blocked VEGF/KDR interaction
      and inhibited VEGF-stimulated activation of KDR expression on human endothelial
      cells. Furthermore, Ycom1D3 efficiently neutralized VEGF-induced mitogenesis of
      human umbilical vascular endothelial cells. CONCLUSION: McAb Ycom1D3 against KDR
      III may suppress the action of VEGF by blocking native vascular endothelial
      growth factor receptor KDR. It has potential clinical applications in the
      treatment of cancers and other diseases where pathological angiogenesis is
      involved.

PMID- 15949418
TI  - [Effect of gastrin on invasiveness of human colon cancer cells].
AB  - OBJECTIVE: To investigate the effect of gastrin on invasiveness of human colon
      cancer cells and the role of gastrin receptor-focal adhesion kinase (FAK) signal
      transduction pathway in this proess. METHODS: pCR3.1/GR vector expressing gastrin
      receptor was transfected into a colorectal cancer cell line Colo320 with
      lipofectamine 2000, and screened by G418. The expression levels of gastrin
      receptor of the parental cell line Colo320 and the transfected cell line
      Colo320/GR were assayed by RT-PCR. On the other hand, antisense oligonucleotide
      of FAK was used to block its expression. The mock transfected Colo320 and sense
      oligonucleotide Colo320 cells were used as controls. Colo320 and Colo320/GR cells
      were treated with increasing doses (0 approximately 100 nmol/L) of gastrin.
      Invasiveness of Colo320 and Colo320/GR cells was determined by Boyden chamber.
      Phosphorylation of focal adhesion kinase (FAK) tyr-397 was examined by
      immunoprecipitation and Western-blot. RESULTS: RT-PCR results showed that the
      Colo320/GR cells had an mRNA level four times as high as that of Colo320 cells.
      Western blot showed that FAK tyr397 phosphorylation of Colo320 cells was
      apparently decreased. Colo320 and Colo320/GR cells showed a dose-dependent
      response to gastrin on invasiveness and phosphorylation of FAK tyr-397.
      Invasiveness of Colo320 cells reached its climax when concentration of gastrin
      was 100 nmol/L, and FAK tyr-397 phosphorylation was marked when concentration of
      gastrin was 10 nmol/L, but the latter decreased when gastrin concentration was
      increased to 100 nmol/L. Colo320/GR cells had the same tendency as Colo320 cells,
      but showed an even stronger invasiveness and a higher level of FAK tyr-397
      phosphorylation than Colo320 cells. Before gastrin stimulation, the invasiveness
      of Colo320 cells transfected with antisense oligonucleotides and the controls
      showed no difference. After gastrin stimulation, the increase in invasiveness was
      much less than that in the controls. CONCLUSION: Gastrin can evidently promote
      invasiveness of Colo320 cells via gastrin-gastrin receptor-FAK signal
      transduction pathway.

PMID- 15949419
TI  - [Construction of PTEN eukaryotic expression plasmid and its effects on breast
      carcinoma cell line MDA468].
AB  - OBJECTIVE: To investigate the effects of exogenous wild PTEN gene stably
      transfection on growth of breast cancer cells in vitro. METHODS: At first, a
      recombinant eukaryotic expression plasmid pcDNA3.1-PTEN was constructed. Human
      breast cancer cell line MDA468 was transfected with pcDNA3.1-PTEN or mock
      transfected plasmid pcDNA3.1(-) with lipofectamine. RT-PCR, immunohistochemical
      staining and Western blot were used to determine target gene expression. Cell
      viability was tested by MTT assay. Apoptosis was determined by flow cytometry
      with a double-staining method using FITC-conjugated annexin V and PI. RESULTS:
      The PTEN stably transfected cells demonstrated the integration of the exogenous
      target gene and corresponding mRNA and protein over-expression. There was a
      significant decline in cell viability of pcDNA3.1-PTEN transfected MDA468 cells
      in comparison with the mock-transfected ones (P < 0.01). The PTEN-trasfected
      MDA468 cells also showed an increase in the rate of apoptosis, compared with
      parental and mock-trasfected cells (P < 0.001). CONCLUSION: Stable expression of
      exogenous PTEN can suppress the malignant phenotypes of the human breast cancer
      cell line MDA468.

PMID- 15949422
TI  - [Natural history of small hepatocellular carcinoma: studied by MRI].
AB  - OBJECTIVE: To study natural history of small hepatocellular carcinoma (sHCC) and
      value of MRI in this research. METHODS: From 1999 to 2002, serial MR imagings
      were performed in 192 patients with cirrhosis no less than twice in order to
      detect sHCC focus. Characteristic MRI findings of focus were analysed. Diameters
      of focus (D) were measured. Tumorigenesis detected time (T) was counted; T and D
      were analysed by statistics and tumor volume doubling time (T(d)) was calculated.
      RESULTS: Fifty-eight new tumor foci in 33 patients were found, including 31 foci
      in 23 patients developed on the basis of cirrhosis, with a 12.0% cumulative
      tumorigenic rate of three years. The tumorigenesis detected time (T) was 386.9 +/
      256.4 days and the maximum diameter (D) was 2.258 +/- 1.074 cm. T was
      statistical correlated with D(3) (P < 0.01) and regressive formulas were
      established: D(3) = -2.69 + 0.058T (P = 0.0007), D(3) = -72.13 + 16.04lnT (P =
      0.0064). Tumor volume doubling time was 20 approximately 279 days (mean: 104
      days). CONCLUSION: The percentage of tumorigenesis is high in patients with
      cirrhosis. Regular MRI examinations are necessary to detect sHCC early. The
      optimal interval time is 3 approximately 6 months.

PMID- 15949423
TI  - [Relation between angiogenesis, fibrinolysis and invasion/metastasis in breast
      cancer].
AB  - OBJECTIVE: To investigate the relation between angiogensis, fibrinolysis and
      invasion/metastasis in breast cancer. METHODS: The expression of urokinase-type
      plasminogen activator (uPA) and microvascular density (MVD) was
      immunohistochemically studied in 110 patients with primary breast cancer.
      RESULTS: High uPA expression was found in 59 patients (53.6%), and weak
      expression in 51 patients (46.4%). Strong MVD expression was found in 53 patients
      (48.2%), and weak expression in 57 patients (51.8%). The correlation between uPA
      expression and tumor size, lymph node status, TNM stage was statistically
      significant. Expression of MVD was also significantly associated with tumor size
      and TNM stage. Neither age related to GDDP, menopausal status nor PR ER status
      was significantly with uPA and MVD expression. Patients with strong expression of
      uPA and/or MVD had a significantly shorter relapse-free survival than those with
      weak expression of uPA and/or MVD. Especially, patients with strong expression of
      both uPA and MVD were likely to develop recurrence and metastasis. Multivariate
      analysis showed that uPA and MVD were two independent prognostic factors
      affecting the relapse-free survival. CONCLUSION: Angiogensis and fibrinolysis
      were closely associated with invasion and metastasis of breast cancer. uPA and
      MVD may be two strong and independent biologic markers in predicting
      postoperative relapse and metastasis of breast cancer.

PMID- 15949424
TI  - [Expression and clinical significance of KISS-1 and GPR54 mRNA in endometrial
      carcinoma].
AB  - OBJECTIVE: To investigate the expression and clinical significance of KISS-1 mRNA
      and GPR54 mRNA in endometrial carcinoma. METHODS: The expression of KISS-1 mRNA
      and GPR54 mRNA in 32 patients with endometrial carcinoma, 10 patients with
      endometrial intraepithelial neoplasia (EIN) and 12 patients with normal
      endometrium was detected by reverse transcriptase polymerase chain reaction (RT
      PCR). RESULTS: The positive rate of KISS-1 mRNA in endometrial carcinoma, EIN and
      normal endometrium was 37.5%, 80.0% and 83.3% respectively (endometrial carcinoma
      vs EIN or normal endometrium, P < 0.05). The expression of KISS-1mRNA in patients
      with endometrial carcinoma was correlated with its clinical stage, myometrial
      invasion and lymph node metastasis (P < 0.05). In endometrial carcinoma, the more
      advanced clinical stage, the lower expression of KISS-1 mRNA was detected. The
      positive rate of GPR54 mRNA in endometrial carcinoma, EIN and normal endometrium
      was 78.1%, 70.0% and 66.7% respectively, with no significant statistical
      difference (P > 0.05). It was not correlated with the clinical stage, histology
      grade, myometrial invasion or lymph node metastasis (P > 0.05). CONCLUSION: The
      interaction of KISS-1 and GPR54 may play an important role in inhibiting the
      invasion and metastasis of endometrial carcinoma.

PMID- 15949425
TI  - [COX-2 expression in the H. pylori infected gastric mucosal epithelia and its
      significance].
AB  - OBJECTIVE: To study COX-2 expression in H. pylori infected gastric mucosal
      epithelia and its significance in the carcinogenesis of the stomach. METHODS:
      Rapid urease test and histological examination with basic magnenta staining were
      used to assess the status of H. pylori infection in the stomach. COX-2 was
      detected immunohistochemically. RESULTS: COX-2 immunostaining was positive in 1
      out of 12 cases with H. pylori-negative gastric mucosa and also in 1 out of 10
      cases with H. pylori-positive gastric mucosa without macroscopic alterations,
      while COX-2 expression was found to be positive in 5 out of 9 cases with H.
      pylori related superficial gastritis with mucosal erosions. COX-2 expression was
      detected in 5 out of 10 cases with H. pylori-positive mild atrophic gastritis, 8
      out of 10 cases with H. pylori-positive moderate-severe atrophic gastritis and
      intestinal metaplasia, and 6 out of 8 cases with H. pylori-positive moderate
      severe dysplasia. COX-2 expression was positive in 22 out of 32 cases of gastric
      cancer. CONCLUSION: H. pylori may induce COX-2 expression of gastric mucosal
      epithelia in chronic superficial gastritis, which is related to the development
      of mucosal injury. According to gastric mucosal carcinogenesis pattern up
      regulation of COX-2 expression is associated with gastric mucosal carcinogenesis,
      and involved in the early development of premalignant lesions.

PMID- 15949426
TI  - [Correlation between pathology and image characteristics of retroperitoneal
      liposarcoma].
AB  - OBJECTIVE: To investigate the correlation between the pathological and image
      features of different subtypes of retroperitoneal liposarcoma. METHODS:
      Pathological and image characteristics of 21 retroperitoneal liposarcomas were
      retrospectively analyzed comparing their different histopathological subtypes.
      RESULTS: This series consisted of 11 well-differentiated, 4 myxoid, 3 round-cell,
      2 pleomorphic and 1 dedifferentiated liposarcoma. Well-differentiated
      liposarcomas were predominantly composed of lipoma-like and sclerosing
      components. On CT and MRI image, the attenuation and signal intensity of lipoma
      like components resembled those of fat, whereas the signal intensity of
      sclerosing components was similar to those of muscle. Unenhanced CT image of the
      myxoid subtype showed density resembling that of water. On contrast-enhanced CT
      image, it showed gradual reticular or sheet-like enhancement. The CT and MRI
      image appearance of the round cell and pleomorphic subtypes resembled those of
      nonfatty soft tissue masses with foci of necrosis. The dedifferentiated
      liposarcoma showed the image feature of a well-differentiated component clearing
      enhanced soft tissue mass. CONCLUSION: Different subtypes of retroperitoneal
      liposarcoma show different CT and MRI features relating to their major histologic
      components. A good understanding of the relation between their radiological and
      pathological features is helpful to arrive at a correct diagnosis for
      retroperitoneal liposarcoma.

PMID- 15949427
TI  - [Clinical value of esophageal mucosal iodine stain during esophagoscopy for
      patients without swallowing symptoms].
AB  - OBJECTIVE: To investigate the clinical value of esophageal mucosal iodine stain
      during esophagoscopy for patients with early esophageal carcinoma or precancerous
      lesions without swallowing symptoms, through analyzing the correlation between
      endoscopic findings and pathological results of biopsy on the suspicious spots.
      METHODS: For 366 patients examined by iodine stain during esophagoscopy, the
      position, size, shape and boundary of all visible unstained lesions were recorded
      and multiple biopsies were taken on the unstained spots. RESULTS: Before iodine
      stain, 462 lesions had been discovered in 366 patients. However, 478 abnormal
      lesions stained in 341 patients were detected after iodine stain, the remaining
      25 gave no abnormal findings. More than 1/3 of patients were found to have more
      than 2 abnormally stained lesions. 28.4% of them (104 cases) had moderate or
      severe dysplasia or early esophageal cancer. The sensitivity of iodine stain in
      this series was 89.8%. CONCLUSION: Iodine stain is very useful in detecting
      occult early esophageal carcinoma and precancerous lesions. The degree of
      coloration and the margin of suspicious spots are closely correlated with the
      pathological results.

PMID- 15949429
TI  - [Preliminary results of radiosurgery for uveal melanoma].
AB  - OBJECTIVE: To evaluate the clinical value of stereotactic radiosurgery (SRS) for
      uveal melanoma. METHODS: From Jan, 1996 to March, 2004, 16 patients with uveal
      melanoma were treated with SRS, two by one session (35 Gy, 25 Gy) and fourteen by
      fractionated SRS (30-55 Gy/2-4F/4-16D). The follow-up period ranged from 3 to 100
      months (median: 66 months). RESULTS: All 16 patients were still alive though all
      were blind in the diseased eye during recent follow-up. Local control rate was
      93.4%, 5-year survival rate of 13 patients who have been followed for more than 5
      years, was 100% (13/13). However, 7 patients received eyeball enucleation due to
      corneal ulcer (n = 2), suspicion for uncontrolled tumor (n = 2) and secondary
      glaucoma (n = 3). One patient developed distant metastasis, though still alive.
      CONCLUSION: Fractionated radiosurgery is safe and effective for uveal melanoma.
      It is indicated for lesions of limited size (longest diameter < 20 mm, depth < 15
      mm) located in the posterior pole or behind the equator at the back of the
      eyeball.

PMID- 15949430
TI  - [Clinical analysis of 91 cases of hereditary breast and ovarian cancer].
AB  - OBJECTIVE: To explore the clinical characteristics of ovarian cancer in
      hereditary breast/ovarian cancer. METHODS: Ninety-one cases of hereditary
      breast/ovarian cancer were analyzed in terms of age, histological features,
      stage, familial history, survival time and prognostic factors by SPSS statistical
      software. RESULTS: The overall median survival time of the patients was 47
      months, and the 2-and 5-year survival rates were 71.2% and 33.5%, respectively.
      The median age at diagnosis of ovarian cancer was 52 years with the majority of
      patients (60.4%) diagnosed before 55. Among 39 cases with double primary cancers,
      there are 20 cases (51.3%) with interval no less than 60 months. The most
      frequent histological types of ovarian cancer is serous adeno-carcinoma (59.3%).
      Most patients were in stage III or IV (76.9%) with poor differentiation (59.3%).
      CONCLUSION: The age of diagnosis in ovarian cancer in patients with hereditary
      breast/ovarian cancer is earlier than that of sporadic ones. Most of the cases
      were advanced with poor differentiation. Stage and differentiation are the
      prognostic factors. In patients with double primary cancers, the clinical
      pathological characteristics of ovarian cancer had the main effect on their
      prognosis. The survival of hereditary ovarian cancer is similar to that of
      sporadic ones.

PMID- 15949431
TI  - [Evaluation of combined percutaneous radio-frequency ablation and percutaneous
      ethanol injection after transcatheter arterial chemoembolization for
      hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the therapeutic effect of combined CT-guided percutaneous
      radio-frequency ablation (RFA) plus percutaneous ethanol injection (PEI) on
      nonresectable priminary hepatocellular carcinoma (HCC) after transcatheter
      arterial chemoembolization (TACE). METHODS: One hundred fifty patients diagnosed
      as HCC either by pathology or by AFP combined with typical CT and angiographic
      image findings were studied, 99 men and 51 women, with an average of 51 years.
      Each patient had at least 3 lesions, ranging from 3.1 to 7.9 cm in diameter,
      average 5.0 cm. All patients were randomly divided into group A (control group)
      and group B (combination group) according to their check-in date (odd or even).
      In group A, 74 patients were treated with RFA alone two weeks after TACE. In
      group B, 76 patients were treated with RFA plus PEI two weeks after TACE.
      RESULTS: The complete necrosis rate was 75.8% in group A and 89.5% in group B (P
      < 0.05). CONCLUSION: The clinical therapeutic effect of radiofrequency ablation
      (RFA) combined with percutaneous ethanol injection (PEI) is better than that of
      RFA alone after TACE in HCC.

PMID- 15949432
TI  - [Surgical treatment of 475 patients with periampullary carcinoma].
AB  - OBJECTIVE: To compare of the outcome of all patients who received surgical
      treatment in one institute for periampullary carcinoma during different intervals
      over the past 40 years. METHODS: Retrospective review of 475 patients suffering
      from periampullary carcinoma in intervals 1958 approximately 1976, 1977
      approximately 1987, 1988 approximately 1998 and 1999 approximately 2003 is
      presented. RESULTS: In interval 1958 approximately 1976, for 128 patients, the
      tumor resection rate was: pancreatic carcinoma (PC) 26.6% (21/79), ampullary
      carcinoma (AC) 86.2% (25/29), distal bile duct cancer (DBDC) 38.5% (5/13), and
      duodenal cancer (DC) 57.1% (4/7). In interval 1977 approximately 1987, for 70
      patients, the tumor resection rate was: PC 26.7% (16/60), AC 66.7% (4/6), DBDC
      100% (1/1), and DC 66.7% (2/3). In interval 1988 approximately 1998, for 147
      patients, the tumor resection rate was: PC 20.2% (22/109), AC 75.0% (12/16), DBDC
      50.0% (2/4), and DC 66.7% (12/18). In interval 1999 approximately 2003, for 130
      patients, the tumor resection rate was: PC 20.4% (20/98), AC 100% (4/4), DBDC
      75.0% (12/16), and DB 83.3% (10/12). Cumulatively, from 1958 to 2003, the
      incidence of DBDC has become significantly higher, and the average of total
      bilirubin level (TBIL) has gradually been going downward, the average of blood
      transfusion during operation and the diameter of resected tumor has been becoming
      smaller. From 1999 to 2003, none of the 130 periampullary carcinoma patients had
      received biliary drainage before operation. CONCLUSION: Mortality and
      complication have become significantly lower because of effective improvement in
      the perioperative preparation and the care after surgery of periampullary cancer
      in the recent years. Even though the accurate diagnosis has become increasing
      earlier than before, the resection rate and prognosis of periampullary carcinoma
      remain poor.

PMID- 15949434
TI  - The D box asserts itself.
AB  - New findings (Burton et al., 2005; Kraft et al., 2005) demonstrate the direct
      recognition of D and KEN boxes, short sequence elements in substrates of the
      anaphase-promoting complex/cyclosome (APC/C), by APC/C coactivators and indicate
      a special role for the D box in the assembly of catalytically active APC/C.

PMID- 15949435
TI  - Tag-team SUMO wrestling.
AB  - Structural and kinetic studies of a SUMORanGAP1-Ubc9-Nup358/RanBP2 complex
      (Reverter and Lima, 2005) provide the first high-resolution view of SUMO
      recognition by a SUMO binding motif and also reveal a novel mechanism for E3
      ubiquitin-like protein ligases, with the Nup358/RanBP2 E3 teaming up with both
      SUMO and the E2 (Ubc9) to stimulate tagging.

PMID- 15949436
TI  - Recombination at collapsed replication forks: the payoff for survival.
AB  - Recombination is believed to assist replication when forks collapse. By using an
      elegant system, Lambert et al. (2005) address the consequences of recombination
      at blocked forks. They show that chromosomal rearrangements are the price to pay
      for cell viability when forks collapse.

PMID- 15949437
TI  - Chromatin in need of a fix: phosphorylation of H2AX connects chromatin to DNA
      repair.
AB  - A bevy of recent reports have firmly established a mechanistic link between a
      histone posttranslational modification associated with DNA double-strand breaks
      and recruitment of chromatin-modifying activities. These papers show that in
      addition to providing signals for transcriptional regulation, specific histone
      "codes" can coordinate and target multiple activities involved in DNA repair.

PMID- 15949438
TI  - Binding of pRB to the PHD protein RBP2 promotes cellular differentiation.
AB  - pRB can enforce a G1 block by repressing E2F-responsive promoters. It also
      coactivates certain non-E2F transcription factors and promotes differentiation.
      Some pRB variants activate transcription and promote differentiation despite
      impaired E2F binding and transcriptional repression capabilities. We identified
      RBP2 in a screen for proteins that bind to such pRB variants. RBP2 resembles
      other chromatin-associated transcriptional regulators and RBP2 binding tracked
      with pRB's ability to activate transcription and promote differentiation. RBP2
      and pRB colocalize and pRB/RBP2 complexes were detected in chromatin isolated
      from differentiating cells. RBP2 siRNA phenocopied restoration of pRB function in
      coactivation and differentiation assays, suggesting that pRB prevents RBP2 from
      repressing genes required for differentiation. In addition, two bromodomain
      containing proteins were identified as RBP2 targets that are transcriptionally
      activated by pRB in an RBP2-dependent manner. Our results suggest that promotion
      of differentiation by pRB involves neutralization of free RBP2 and
      transcriptional activation of RBP2 targets linked to euchromatin maintenance.

PMID- 15949439
TI  - The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax
      conformational change and cell death.
AB  - Tumor cells typically resist programmed cell death (apoptosis) induced by death
      receptors. Activated death receptors evoke Bax conformational change, cytochrome
      c release, and cell death. We report that the tumor suppressor gene RASSF1A is
      required for death receptor-induced Bax conformational change and apoptosis.
      TNFalpha or TRAIL stimulation induced recruitment of RASSF1A and MAP-1 to
      receptor complexes and promoted complex formation between RASSF1A and the BH3
      like protein MAP-1. Normally, MAP-1 is inhibited by an intramolecular
      interaction. RASSF1A/MAP-1 binding relieved this inhibitory interaction,
      resulting in MAP-1 association with Bax. Deletion of the RASSF1A gene or short
      hairpin silencing of either RASSF1A or MAP-1 expression blocked MAP-1/Bax
      interaction, Bax conformational change and mitochondrial membrane insertion,
      cytochrome c release, and apoptosis in response to death receptors. Our findings
      identify RASSF1A and MAP-1 as important components between death receptors and
      the apoptotic machinery and reveal a potential link between tumor suppression and
      death receptor signaling.

PMID- 15949440
TI  - A bidirectional origin of replication maps to the major noncoding region of human
      mitochondrial DNA.
AB  - In solid tissues of vertebrates, initiation of mitochondrial DNA replication
      encompasses a broad zone downstream of the major noncoding region (NCR). In
      contrast, analysis with two-dimensional agarose gel electrophoresis of
      mitochondrial DNA replication intermediates in cultured human cells revealed
      initiation concentrated in the NCR. Mapping of prominent free 5' ends on the
      heavy strand of mitochondrial DNA identified two clusters of potential start
      sites. One mapped to the previously assigned origin of strand-asynchronous
      replication (O(H)); the other lay several hundred nucleotides away from O(H),
      toward the other end of the NCR. The latter cluster is proposed to be the major
      site of bidirectional replication initiation on the basis of the following: its
      prominence is enhanced in cells amplifying mitochondrial DNA after experimentally
      induced mitochondrial DNA depletion; free 5' ends are found in corresponding
      positions on the opposite strand; it is transient in nature; and it is associated
      with bubble arcs.

PMID- 15949441
TI  - Mechanism for the disassembly of the posttermination complex inferred from cryo
      EM studies.
AB  - Ribosome recycling, the disassembly of the posttermination complex after each
      round of protein synthesis, is an essential step in mRNA translation, but its
      mechanism has remained obscure. In eubacteria, recycling is catalyzed by RRF
      (ribosome recycling factor) and EF-G (elongation factor G). By using cryo
      electron microscopy, we have obtained two density maps, one of the RRF bound
      posttermination complex and one of the 50S subunit bound with both EF-G and RRF.
      Comparing the two maps, we found domain I of RRF to be in the same orientation,
      while domain II in the EF-G-containing 50S subunit is extensively rotated
      (approximately 60 degrees) compared to its orientation in the 70S complex.
      Mapping the 50S conformation of RRF onto the 70S posttermination complex suggests
      that it can disrupt the intersubunit bridges B2a and B3, and thus effect a
      separation of the two subunits. These observations provide the structural basis
      for the mechanism by which the posttermination complex is split into subunits by
      the joint action of RRF and EF-G.

PMID- 15949442
TI  - Splitting of the posttermination ribosome into subunits by the concerted action
      of RRF and EF-G.
AB  - After peptide release by a class-1 release factor, the ribosomal subunits must be
      recycled back to initiation. We have demonstrated that the distance between a
      strong Shine-Dalgarno (SD) sequence and a codon in the P site is crucial for the
      binding stability of the deacylated tRNA in the P site of the posttermination
      ribosome and the in-frame maintenance of its mRNA. We show that the elongation
      factor EF-G and the ribosomal recycling factor RRF split the ribosome into
      subunits in the absence of initiation factor 3 (IF3) by a mechanism that requires
      both GTP and GTP hydrolysis. Taking into account that EF-G in the GTP form and
      RRF bind with positive cooperativity to the free 50S subunit but with negative
      cooperativity to the 70S ribosome, we suggest a mechanism for ribosome recycling
      that specifies distinct roles for EF-G, RRF, and IF3.

PMID- 15949443
TI  - Structural determinants for selective recognition of a Lys48-linked polyubiquitin
      chain by a UBA domain.
AB  - Although functional diversity in polyubiquitin chain signaling has been ascribed
      to the ability of differently linked chains to bind in a distinctive manner to
      effector proteins, structural models of such interactions have been lacking.
      Here, we use NMR to unveil the structural basis of selective recognition of Lys48
      linked di- and tetraubiquitin chains by the UBA2 domain of hHR23A. Although the
      interaction of UBA2 with Lys48-linked diubiquitin involves the same hydrophobic
      surface on each ubiquitin unit as that utilized in monoubiquitin:UBA complexes,
      our results show how the "closed" conformation of Lys48-linked diubiquitin is
      crucial for high-affinity binding. Moreover, recognition of Lys48-linked
      diubiquitin involves a unique epitope on UBA, which allows the formation of a
      sandwich-like diubiqutin:UBA complex. Studies of the UBA-tetraubiquitin
      interaction suggest that this mode of UBA binding to diubiquitin is relevant for
      longer chains.

PMID- 15949444
TI  - Ubiquitylation of RAG-2 by Skp2-SCF links destruction of the V(D)J recombinase to
      the cell cycle.
AB  - The periodic destruction of RAG-2 at the G1-to-S transition couples V(D)J
      recombination to the G0 and G1 cell cycle phases and coordinates RAG-mediated DNA
      cleavage with DNA repair by nonhomologous end joining. To define the mechanism by
      which this occurs, we reproduced cell cycle-dependent regulation of the V(D)J
      recombinase in a cell-free system. The ubiquitin-proteasomal pathway carries out
      destruction of RAG-2 in lysates of S phase cells and during S phase in vivo.
      Remarkably, the Skp2-SCF ubiquitin ligase, which plays a central role in cell
      cycle regulation through the destruction of p27, mediates ubiquitylation of RAG-2
      in vitro and degradation of RAG-2 in vivo. The regulation of antigen receptor
      gene assembly by Skp2-SCF provides an unexpected and direct mechanistic link
      between DNA recombination and the cell cycle.

PMID- 15949445
TI  - Interdependence between transcription and mRNP processing and export, and its
      impact on genetic stability.
AB  - The conserved eukaryotic THO-TREX complex acts at the interface between
      transcription and mRNA export and affects transcription-associated recombination.
      To investigate the interdependence of nuclear mRNA processes and their impact on
      genomic integrity, we analyzed transcript accumulation and recombination of 40
      selected mutants covering representative steps of the biogenesis and export of
      the messenger ribonucleoprotein particle (mRNP). None of the mutants analyzed
      shared the strong transcript-accumulation defect and hyperrecombination of THO
      mutants. Nevertheless, mutants in 3' end cleavage/polyadenylation, nuclear
      exosome, and mRNA export showed a weak but significant effect on recombination
      and transcript accumulation. Mutants of the nuclear exosome (rrp6) and 3' end
      processing factors (rna14 and rna15) showed inefficient transcription elongation
      and genetic interactions with THO. The results suggest a tight interdependence
      among mRNP biogenesis steps and transcription and an unexpected effect of the
      nuclear exosome and the cleavage/polyadenylation factors on transcription
      elongation and genetic integrity.

PMID- 15949446
TI  - Dynamic lysine methylation on histone H3 defines the regulatory phase of gene
      transcription.
AB  - Covalent modifications to histones are key epigenetic marks that control gene
      transcription. Multiple lysine residues on histone H3 are methylated (me), but
      their functions are unclear. Here, we demonstrate two phases of combinatorial and
      dynamic H3 methylation during induction of transcription at MET16 in yeast. K4me3
      with K36me2/3 define a postinitiation regulatory phase and precede the appearance
      of K4me2 with K79me2 at the onset of transcript elongation. The Isw1 ATPase
      delays the release of initiated RNA polymerase II (RNAPII) into elongation to
      facilitate chromatin modifications. The Spp1 subunit of complex associated with
      Set1 (COMPASS) and Set2, determining K4me3 and K36me2/3, respectively, are
      required for transient NuA4-dependent H4K8ac. This releases RNAPII from Isw1
      control and promotes controlled transcription elongation and termination. We
      propose that newly initiated RNAPII is under epigenetic control.

PMID- 15949447
TI  - Intrinsic histone-DNA interactions and low nucleosome density are important for
      preferential accessibility of promoter regions in yeast.
AB  - In yeast cells, preferential accessibility of the HIS3-PET56 promoter region is
      determined by a general property of the DNA sequence, not by defined sequence
      elements. In vivo, this region is largely devoid of nucleosomes, and
      accessibility is directly related to reduced histone density. The HIS3-PET56 and
      DED1 promoter regions associate poorly with histones in vitro, indicating that
      intrinsic nucleosome stability is a major determinant of preferential
      accessibility. Specific and genome-wide analyses indicate that low nucleosome
      density is a very common feature of yeast promoter regions that correlates poorly
      with transcriptional activation. Thus, the yeast genome is organized into
      structurally distinct promoter and nonpromoter regions whose DNA sequences
      inherently differ with respect to nucleosome formation. This organization ensures
      that transcription factors bind preferentially to appropriate sites in promoters,
      rather than to the excess of irrelevant sites in nonpromoter regions.

PMID- 15949448
TI  - The covariance between the number of accidents and the number of victims in
      multivariate analysis of accident related outcomes.
AB  - In this study some statistical issues involved in the simultaneous analysis of
      accident related outcomes of the road traffic process are investigated. Since
      accident related outcomes like the number of victims, fatalities or accidents
      show interdependencies, their simultaneous analysis requires that these
      interdependencies are taken into account. One particular interdependency is the
      number of fatal accidents that is always smaller than the number of fatalities as
      at least one fatality results from a fatal accident. More generally, when the
      number of accidents increases, the number of people injured as a result of these
      accidents will also increase. Since dependencies between accident related
      outcomes are reflected in the variance-covariance structure of the outcomes, the
      main focus of the present study is on establishing this structure. As this study
      shows it is possible to derive relatively simple expressions for estimates of the
      variances and covariances of (logarithms of) accidents and victim counts. One
      example reveals a substantial effect of the inclusion of covariance terms in the
      estimation of a confidence region of a mortality rate. The accuracy of the
      estimated variance-covariance structure of the accident related outcomes is
      evaluated using samples of real life accident data from The Netherlands.
      Additionally, the effect of small expected counts on the variance estimate of the
      logarithm of the counts is investigated.

PMID- 15949449
TI  - The world's first automobile fatality.
AB  - The first recorded automobile fatality occurred in a small town in the Irish
      Midlands in 1869. Mary Ward, a celebrated microscopist, artist, astronomer and
      naturalist, fell from a steam carriage and died after crush injuries from its
      heavy iron wheels. The story of first automobile fatality characterizes the
      individual tragedy that is each premature death. It also illuminates the story of
      a remarkable Victorian scientific family. Among their many achievements was the
      building of a reflector telescope in the heart of rural Ireland that was the
      largest in the world for 74 years.

PMID- 15949450
TI  - Impaired driving and motor vehicle crashes among Swedish youth: an investigation
      into drivers' sociodemographic characteristics.
AB  - Impaired driving is an important road safety problem, and the characteristics of
      drivers impaired by alcohol or drugs are relevant to targeted interventions. This
      study considers young drivers' sociodemographic attributes: age, sex, class of
      origin and educational attainment, based on a national cohort of young Swedish
      drivers (1988-2000) followed up in police registers for their first motor vehicle
      crash. Of all crashes reported for these drivers, 946 were where the driver was
      suspected of being under the influence of alcohol or other substances
      (corresponding to 6% of all first crashes). Impaired driving significantly
      increases the odds of severe and fatal injuries, regardless of sociodemographic
      attributes. Observed differences in the proportions of impaired drivers reveal
      significant excess risks among males, persons aged 18-19, those from households
      classified as "workers" and "others" (including, e.g. the long-term unemployed
      and those on long-term sick leave), and those with low educational attainment.
      Impaired driving is a risk factor in all sociodemographic strata among young
      people. Members of some groups are more likely to be found than others among
      impaired drivers on occasion of first motor vehicle crash.

PMID- 15949451
TI  - Self-rated driving performance among elderly drivers referred for driving
      evaluation.
AB  - PURPOSE: To explore whether elderly drivers of varying driving skill levels (1)
      differ in their perception of their driving evaluation performance and (2)
      determine if self-rated driving evaluation performance is related to cognitive
      ability. METHODS: One hundred and fifty-two drivers aged 65 years or older and
      referred for a driving evaluation were enrolled into the study. Subjects were
      asked the question, "how well do you think you will perform today on your driving
      evaluation compared to others your own age?" Subjects also completed the Mini
      Mental State Exam and a 30-min drive on a STISIM Drivetrade mark simulation
      (Systems Technology, Inc., Hawthorne, CA). Only 47 subjects completed both the
      simulated drive and self-rated item. RESULTS: Sixty-five percent of drivers rated
      themselves as performing better on a driving test than others of their age.
      Another 31.9% felt they would perform the same as others of their age on a
      driving test. A 50.0% of those considering themselves "a little better" and 52.9%
      of those considering themselves "a lot better" had an unsafe driving performance.
      As self-rated driving evaluation performance increased, there was a significantly
      increased risk of unsafe driving (p=0.02) in the study population. Drivers who
      considered themselves at least a little better than others of their age were over
      four times more likely to be unsafe drivers compared to others who believed they
      were comparable to or worse than other drivers of their age (RR=4.13, 95% CI=1.08
      15.78). There was no significant difference in MMSE between self-rating groups
      (p=0.76). CONCLUSION: Older drivers assign high ratings to their driving
      performance, even in the presence of suspected skill decline. Cognitive ability
      was not related to self-rated driving evaluation performance.

PMID- 15949452
TI  - Risky driving habits and motor vehicle driver injury.
AB  - Risky driving is an important cause of motor vehicle injury, but there is a lack
      of good epidemiological data in this field, particularly data comparing risky
      driving in younger drivers to those of other age groups. We examined the
      relationship between risky driving habits, prior traffic convictions and motor
      vehicle injury using cross-sectional data amongst 21,893 individuals in New
      Zealand, including 8029 who were aged 16-24 years. Those who reported frequently
      racing a motor vehicle for excitement or driving at 20 km/h or more over the
      speed limit, and those who had received traffic convictions over the past 12
      months, were between two and four times more likely to have been injured while
      driving over the same time period. Driving unlicensed was a risk factor for older
      but not younger drivers, and driving at 20 km/h or more above the speed limits
      was a stronger risk factor for younger (<25 years) than older drivers. These
      results confirm the need for interventions targeting risky driving and suggest
      that different strategies may be required for different high-risk groups.

PMID- 15949453
TI  - Suicide prevention through means restriction: assessing the risk of substitution.
      A critical review and synthesis.
AB  - The effectiveness of restricting access to certain means of committing suicide
      has been demonstrated, at least as regards toxic domestic gas, firearms, drugs
      and bridges. At the individual level, studies tend to indicate that many persons
      have a preference for a given means, which would limit the possibility of
      substitution or displacement towards another method. Similarly, the fact that
      suicidal crisis are very often short-lived (and, what is more, influenced by
      ambivalence or impulsiveness) suggests that an individual with restricted access
      to a given means would not put off his plans to later or turn to alternative
      methods. This has been more difficult to demonstrate scientifically in population
      studies. Nevertheless, it appears that, should such a shift occur towards other
      means, it would be put into effect only in part and over a longer term.

PMID- 15949454
TI  - Effects of vehicle bumper height and impact velocity on type of lower extremity
      injury in vehicle-pedestrian accidents.
AB  - In nonfatal passenger vehicle-pedestrian accidents, the lower extremities are the
      most commonly injured body parts. The European Enhanced Vehicle-safety Committee
      Working Group 17 (EEVC/WG17) pedestrian subsystem test method using a legform
      impactor has been developed mainly for evaluation of aggressiveness of the front
      bumper of passenger vehicles. However, in recent years the number of sports
      utility vehicles (SUV) with a high bumper has been rapidly increasing. Since the
      bumper height is different between a passenger vehicle and an SUV, the type of
      lower extremity injury may be different. The type of lower extremity injury
      caused by this different bumper height should be clarified, because the test
      method and vehicle safety countermeasure must take into account a certain type of
      injury. Furthermore, the effect of vehicle impact velocity on the type of lower
      extremity injury in vehicle-pedestrian accidents has not been investigated so
      far. Therefore, the objective of this study is to clarify the effect of vehicle
      bumper height and vehicle impact velocity on the type of lower extremity injury
      in vehicle-pedestrian accidents. The Pedestrian Crash Data Study (PCDS), an in
      depth accident database in the USA, was used for the current analyses. The
      results indicate that the type of injury, i.e., to the tibia and knee ligament,
      could become an injury to the femur with an increase in bumper height.
      Furthermore, the main injury at an impact velocity of around 20-30km/h is to the
      knee ligament. On the other hand, the main injury at an impact velocity of around
      40km/h is a fracture of the lower extremities.

PMID- 15949455
TI  - The Fatality Analysis Reporting System as a tool for investigating racial and
      ethnic determinants of motor vehicle crash fatalities.
AB  - The Fatality Analysis Reporting System (FARS) is a Department of Transportation
      database in the public domain that contains detailed information about fatalities
      resulting from motor vehicle crashes on public roadways in the United States
      since 1975. However, data on race and Hispanic ethnicity were not collected by
      FARS until 1999. Since then, completeness of reported racial and ethnic
      information has varied from State to State. To assess utility of FARS for
      investigating race- and ethnicity-specific risk factors associated with motor
      vehicle crash mortality, we examined yearly national and State-specific reporting
      rates of race and Hispanic ethnicity for 168,863 motor vehicle crash fatalities
      from 1999 to 2002. In 1999, national reporting was 85% for race and 78% for
      Hispanic ethnicity. Over the 4-year study period, a significant linear increase
      in annual reporting for both race and Hispanic ethnicity was evident at the
      national level, as reporting by individual States improved over time. In 2002,
      national reporting rates reached 90% for race and 88% for Hispanic ethnicity. Our
      findings indicate that FARS has become a valuable resource for population-based
      studies of motor vehicle crash mortality disparities that exist among racial and
      ethnic subpopulations in the United States.

PMID- 15949456
TI  - Epidemiology of child pedestrian casualty rates: can we assume spatial
      independence?
AB  - Child pedestrian injuries are often investigated by means of ecological studies,
      yet are clearly part of a complex spatial phenomena. Spatial dependence within
      such ecological analyses have rarely been assessed, yet the validity of basic
      statistical techniques rely on a number of independence assumptions. Recent work
      from Canada has highlighted the potential for modelling spatial dependence within
      data that was aggregated in terms of the number of road casualties who were
      resident in a given geographical area. Other jurisdictions aggregate data in
      terms of the number of casualties in the geographical area in which the collision
      took place. This paper contrasts child pedestrian casualty data from Devon County
      UK, which has been aggregated by both methods. A simple ecological model, with
      minimally useful covaraties relating to measures of child deprivation, provides
      evidence that data aggregated in terms of the casualty's home location cannot be
      assumed to be spatially independent and that for analysis of these data to be
      valid there must be some accounting for spatial auto-correlation within the model
      structure. Conversely, data aggregated in terms of the collision location (as is
      usual in the UK) was found to be spatially independent. Whilst the spatial model
      is clearly more complex it provided a superior fit to that seen with either
      collision aggregated or non-spatial models. Of more importance, the ecological
      level association between deprivation and casualty rate is much lower once the
      spatial structure is accounted for, highlighting the importance using
      appropriately structured models.

PMID- 15949457
TI  - Firearm storage practices and rates of unintentional firearm deaths in the United
      States.
AB  - BACKGROUND: The American Academy of Pediatrics and the American Medical
      Association recommend storing firearms unloaded and locked up to minimize the
      chance of injury. Although these recommendations appeal to common sense, no study
      has yet addressed whether firearm storage practices influence the risk of
      unintentional firearm injury. METHODS: Negative binomial regression analyses were
      used to assess the cross sectional relation between firearm storage practices and
      rates of unintentional firearm death in the United States, controlling for rates
      of firearm prevalence, poverty and urbanization. Recently available state-level
      measures of household firearm prevalence and firearm storage practices were
      obtained from the 2002 Behavioral Risk Factor Surveillance System. Unintentional
      firearm death counts and population data came from the National Center for Health
      Statistics. RESULTS: Independent of firearm prevalence, urbanization, and
      poverty, a disproportionately large share of unintentional firearm fatalities
      occurred in states where gun owners were more likely to store their firearms
      loaded, the greatest risk occurring in states where loaded firearms were more
      likely to be stored unlocked. CONCLUSION: Our findings provide empirical support
      for recommendations issued by the AMA and the AAP that firearms should be stored
      unloaded and locked, and suggest that promoting safer storage practices could
      save many lives.

PMID- 15949458
TI  - Seat position and the risk of serious thoracoabdominal injury in lateral motor
      vehicle crashes.
AB  - CONTEXT: Previous studies have suggested that motor vehicle occupants seated on
      the near-side of a lateral impact have a higher proportion of thoracoabdominal
      injuries. However, due to limitations in previous studies, the true association
      between seat position, side of lateral impact, and thoracoabdominal injury is
      unclear. OBJECTIVE: To assess the relationship between seat position (i.e., near
      side, middle-seat, and far-side, regardless of row), side of lateral motor
      vehicle crash (MVC), and serious thoracoabdominal injury after adjusting for
      important crash factors. DESIGN: National population-based cohort of adult
      subjects involved in MVCs and included in the National Automotive Sampling System
      Crashworthiness Data System database (NASS CDS) from 1995 to 2003. PATIENTS:
      Occupants aged > or =16 years involved in MVCs where the highest external
      deformation of the vehicle was located on the right or left side (i.e., lateral).
      MAIN OUTCOME MEASURE: Serious thoracic or abdominal injury, defined as an
      Abbreviated Injury Scale (AIS) > or =3 in the thoracic or abdominal body region.
      RESULTS: Fifteen thousand, one hundred and sixty persons involved in primary
      lateral MVCs were represented in the NASS CDS database during the 9-year period.
      There were 1867 (2%) persons with serious thoracic injuries and 507 persons
      (0.5%) with serious abdominal injuries. In multivariable logistic regression
      models that adjusted for important crash factors and the NASS CDS sampling
      design, seat position was a strong effect modifier of the association between
      side of lateral impact and serious thoracic (p<0.0001) and abdominal (p=0.0009)
      injury, with the risk of serious thoracic and abdominal injury highest for
      occupants seated on the near-side of the crash. The mean probability of injury
      was higher for near-side and middle-seat occupants compared to far-side
      occupants, and the probability of thoracic injury was approximately four times
      higher than that of abdominal injury for all seat positions. CONCLUSIONS: There
      is a strong, synergistic relationship between seat position and side of lateral
      MVC in assessing risk of serious thoracic and abdominal injury among adult
      occupants. The probability of serious thoracoabdominal injury increases with
      increasing proximity of seat position to side of the crash and the risk of
      thoracic injury is higher than abdominal injury for all seat positions.

PMID- 15949459
TI  - Predicting older drivers' accident involvement--Smeed's law revisited.
AB  - The present study used Swedish archival data on police-reported accidents and
      license statistics and Swedish questionnaire data on car use in order to test an
      underinvolvement hypothesis of older drivers' (65-84 years) accident involvement,
      postulating that the increase in older drivers' accident involvement is smaller
      than the increase in older drivers' presence in traffic. The results gave support
      to the hypothesis. Compared to the accident involvement trend in the general
      driver population, there was a relative decrease over time in older drivers'
      accident involvement per driver license and per active driver from 1983 to 1999.
      It is concluded that linear predictions of older drivers' accident involvement
      directly based on their increasing presence in traffic are likely to be overly
      pessimistic.

PMID- 15949460
TI  - Attributions of responsibility for motor vehicle crashes.
AB  - A sample of 321 motor vehicle crash survivors completed a survey in which they
      provided attribution ratings of the extent to which they were responsible for
      their crashes, other people (drivers) were responsible, or road/weather
      conditions were responsible. The attribution ratings were consistent with the
      predictions of defensive attribution theory (DAT; [Walster, E., 1966. Assignment
      of responsibility for an accident. J. Pers. Soc. Psychol. 3, 73-79]) in that
      people who experienced crashes of greater severity (necessitating medical
      treatment for injuries) attributed greater responsibility to other drivers than
      to self or to weather/road conditions. People who were in crashes of lesser
      severity attributed approximately the same amount of responsibility to themselves
      as they did to others. An actor-observer effect also appeared in survivors'
      attribution ratings in that self-acceptance of responsibility for the crash was
      positively correlated with attributions to the situation (road/weather
      conditions) whereas such attributions to the situation were negatively correlated
      with attributions of responsibility to other drivers. Consistent with results of
      prior research, survivors who assigned crash responsibility to other drivers
      reported increased levels of driving and riding avoidance compared to people who
      accepted responsibility for their crashes.

PMID- 15949461
TI  - Causes and prevention of boating fatalities.
AB  - The aim of this study was to investigate the causes and prevention of the 333
      boating deaths that occurred in Australia over the period 1992-1998. It involved:
      assessment of the Coroner's findings; review of witness statements, police
      reports, autopsy findings, search and rescue reports, weather maps and reports;
      analysis of forensic and scientific data; assessment of photographic evidence;
      review of other related information. The data were coded according to a recently
      developed national data standard. It was found that nearly half of the vessels
      involved had an insufficient number of personal flotation devices for the number
      of people on board; of all people killed only 9% were wearing them, and survivors
      were more than two times more likely to have been wearing them. If usage could be
      increased to 75%, five lives could be saved each year with a cost saving to the
      Australian community of nearly $8 million. The contribution of alcohol to boating
      deaths (28% in excess of 0.05g/100ml) was similar to its contribution to road
      deaths. The sequence of events resulting in a boating death was initiated most
      often by capsize (36%). Capsize was more likely to involve overloading or
      improper loading, hazardous wind or sea conditions, and dinghies. Twenty-five
      percent of the vessels involved in fatalities were dinghies and they were more
      likely to be overloaded, involve capsize, alcohol, and failure to wear a personal
      flotation device. Fatalities involving personal watercraft were mainly caused by
      human factors. Boating causes a significant level of harm to the Australian
      community measured in terms of mortality. This can be reduced by a concerted
      effort to address the identified hazards and protective factors.

PMID- 15949462
TI  - Bayesian ranking of sites for engineering safety improvements: decision
      parameter, treatability concept, statistical criterion, and spatial dependence.
AB  - In recent years, there has been a renewed interest in applying statistical
      ranking criteria to identify sites on a road network, which potentially present
      high traffic crash risks or are over-represented in certain type of crashes, for
      further engineering evaluation and safety improvement. This requires that good
      estimates of ranks of crash risks be obtained at individual intersections or road
      segments, or some analysis zones. The nature of this site ranking problem in
      roadway safety is related to two well-established statistical problems known as
      the small area (or domain) estimation problem and the disease mapping problem.
      The former arises in the context of providing estimates using sample survey data
      for a small geographical area or a small socio-demographic group in a large area,
      while the latter stems from estimating rare disease incidences for typically
      small geographical areas. The statistical problem is such that direct estimates
      of certain parameters associated with a site (or a group of sites) with adequate
      precision cannot be produced, due to a small available sample size, the rareness
      of the event of interest, and/or a small exposed population or sub-population in
      question. Model based approaches have offered several advantages to these
      estimation problems, including increased precision by "borrowing strengths"
      across the various sites based on available auxiliary variables, including their
      relative locations in space. Within the model based approach, generalized linear
      mixed models (GLMM) have played key roles in addressing these problems for many
      years. The objective of the study, on which this paper is based, was to explore
      some of the issues raised in recent roadway safety studies regarding ranking
      methodologies in light of the recent statistical development in space-time GLMM.
      First, general ranking approaches are reviewed, which include naive or raw crash
      risk ranking, scan based ranking, and model based ranking. Through simulations,
      the limitation of using the naive approach in ranking is illustrated. Second,
      following the model based approach, the choice of decision parameters and
      consideration of treatability are discussed. Third, several statistical ranking
      criteria that have been used in biomedical, health, and other scientific studies
      are presented from a Bayesian perspective. Their applications in roadway safety
      are then demonstrated using two data sets: one for individual urban intersections
      and one for rural two-lane roads at the county level. As part of the
      demonstration, it is shown how multivariate spatial GLMM can be used to model
      traffic crashes of several injury severity types simultaneously and how the model
      can be used within a Bayesian framework to rank sites by crash cost per vehicle
      mile traveled (instead of by crash frequency rate). Finally, the significant
      impact of spatial effects on the overall model goodness-of-fit and site ranking
      performances are discussed for the two data sets examined. The paper is concluded
      with a discussion on possible directions in which the study can be extended.

PMID- 15949463
TI  - Is the number of traffic fatalities in American hospitals decreasing?
AB  - Fatality Analysis Reporting System (FARS) data from 1977 to 2002 record a
      decreasing number of traffic fatalities taken to a hospital compared with traffic
      fatalities not taken to a hospital. In this study, we calculated the proportions
      of decedents reportedly taken to a hospital each year in each state, and the
      proportions surviving at least 1h. We also used death certificate data from the
      National Center for Health Statistics (NCHS) for 1979-1999 to categorize the
      proportion of motor vehicle fatalities in each state by hospital patient status.
      The annual number of traffic fatalities decreased slightly over the period of
      observation. The proportion of decedents recorded in FARS as transported to a
      hospital fell from about 73 to 43%. However, this proportion decreased abruptly
      at certain times in some states, suggesting previous misclassification. The
      proportion surviving at least 1h remained relatively constant. NCHS data showed a
      decline in the proportion declared dead in hospitals from 62 to 51%, including a
      decline in the proportion declared dead on arrival (DOA) from 20 to 8%. Along
      with occasional misclassification in some states, the decrease in cases
      transported only to be pronounced DOA could explain why FARS data show a decrease
      in deaths after hospital transport.

PMID- 15949464
TI  - Different quantitative measures of the impact of injury deaths on the community
      in the Guangxi Province, China.
AB  - BACKGROUND: Injury has been identified as a major health problem in China.
      Different quantitative measures based on the concept of years of potential life
      lost have been derived for assessing the burden of injury and other diseases.
      However, few studies have been conducted to compare the usefulness of these
      measures in terms of providing practical information. This study aims to examine
      the utility of different measures in assessing the impact of injury to Chinese
      society. METHODS: This is a population-based epidemiological study utilising
      surveillance and fielded-gathered data. Data are obtained from the disease
      surveillance information system and record on each death certificate. The
      mortality rates, years of potential life lost (YPLL), potentially years of
      productive life lost (PYPLL), and the valued years of potential life lost (VYPLL)
      are calculated and compared for deaths due to injury and other major diseases.
      Data on different causes of injury were analysed in the same manner. RESULTS: In
      comparison to other causes of death, injury deaths had the highest annual rates
      of YPLL (1265.1 years/100,000 persons), PYPLL (517.8 years/100,000 persons), and
      VYPLL (378.6 years/100,000 persons). Premature deaths due to injury provided the
      only positively valued VYPLL among all major causes of death. Among the injury
      deaths, motor vehicle traffic-related death caused the largest YPLL (13,274
      years), PYPLL (5461 years), and VYPLL (3064 years). CONCLUSION: In considering
      the burden of deaths to society, mortality rate only is an insufficient measure.
      The age, the years of overall life and expected productivity and related economic
      consequences have to be taken into consideration. As an indicator of the economic
      impact and burden of premature deaths to society, the VYPLL seems to be an
      advantageous utility. Injury posts the greatest public health problem to the
      developing economy of China.

PMID- 15949465
TI  - Urocortin: a cardiac protective peptide?
AB  - Urocortin (UCN), a member of the corticotropin-releasing hormone (CRH)-related
      peptides, has been reported to play biologically diverse roles in several systems
      such as cardiovascular, reproductive, appetite, stress, inflammatory responses,
      etc. In heart, it was reported to have protective effects. On the other hand, it
      was also reported to have cardiac inotropic and hypertrophic effects and hence to
      cause cardiac remodeling. This paper will review the effects of UCN in cardiac
      system.

PMID- 15949466
TI  - Pleiotrophin induces formation of functional neovasculature in vivo.
AB  - Pleiotrophin (PTN) is a heparin-binding growth/differentiation inducing cytokine
      that shares 50% amino acid sequence identity and striking domain homology with
      Midkine (MK), the only other member of the Ptn/Mk developmental gene family. The
      Ptn gene is expressed in sites of early vascular development in embryos and in
      healing wounds and its constitutive expression in many human tumors is associated
      with an angiogenic phenotype, suggesting that PTN has an important role in
      angiogenesis during development and in wound repair and advanced malignancies. To
      directly test whether PTN is angiogenic in vivo, we injected a plasmid to express
      PTN into ischemic myocardium in rats. Pleiotrophin stimulated statistically
      significant increases in both normal appearing new capillaries and arterioles
      each of which had readily detectable levels of the arteriole marker, smooth
      muscle cell alpha-actin. Furthermore, the newly formed blood vessels were shown
      to interconnect with the existent coronary vascular system. The results of these
      studies demonstrate directly that PTN is an effective angiogenic agent in vivo
      able to initiate new vessel formation that is both normal in appearance and
      function. The data suggest that PTN signals the more "complete" new blood vessel
      formation through its ability to stimulate different functions in different cell
      types not limited to the endothelial cell.

PMID- 15949467
TI  - A physiologic three-dimensional cell culture system to investigate the role of
      decorin in matrix organisation and cell survival.
AB  - In vivo cells exist in a three-dimensional environment generated and maintained
      by multiple cell-cell and cell-matrix interactions. Proteoglycans, like decorin,
      affect these complex interactions. Thus, we sought to investigate the role of
      decorin in a three-dimensional environment where the matrix was generated over
      time by decorin-deficient fibroblasts in the presence of L-ascorbic acid 2
      phosphate. The cells were viable and proliferated in response to FGF2. Decorin
      was incorporated in the matrix and caused a approximately 2 nm shift in the
      average diameter of the collagen fibrils, and the range and distribution of the
      fibrils became narrower and more uniform. Although there were no appreciable
      changes in collagen composition, we found that exogenous decorin induced the de
      novo synthesis of collagen I and V and cross-linked beta(I). In the early phases
      of the three-dimensional culture, decorin reduced apoptosis. However, following
      the establishment of a three-dimensional matrix, the cells did not require
      decorin for their survival.

PMID- 15949468
TI  - Cytokine stimulated vascular cell adhesion molecule-1 (VCAM-1) ectodomain release
      is regulated by TIMP-3.
AB  - OBJECTIVES: Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface adhesion
      molecule involved in the recruitment of leukocytes to endothelial cells on
      arterial walls during the pathogenesis of atherosclerosis. The soluble ectodomain
      of VCAM-1 (sVCAM-1) is proteolytically released from the cell surface into the
      circulation, a process which is up-regulated in patients with cardiovascular or
      inflammatory disease. Here we investigate mechanisms involved in sVCAM-1
      generation in response to cytokine stimulation. METHODS: VCAM-1 ectodomain
      release into the conditioned media of MCEC-1 murine endothelial cells and cells
      grown from primary aortic explants from timp3-/- mice and wild-type littermates
      was measured by sandwich ELISA and Western blot after stimulation with tumor
      necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), or the phorbol
      ester PMA. Protease expression was inhibited (knocked down) with siRNA and
      validated using real-time PCR. RESULTS: Proinflammatory cytokines IL-1beta and
      TNFalpha up-regulated VCAM-1 ectodomain release from the MCEC-1 cells, and this
      was dependant on p38 and mitogen-activated protein kinases (MAP kinases) and
      inhibited by the matrix metalloproteinase (MMP) inhibitor BB94 and tissue
      inhibitor of metalloproteinase (TIMP)-3, but not TIMP-1 or TIMP-2. Timp-3-/-
      cells exhibited greater VCAM-1 ectodomain release following cytokine stimulation
      than TIMP-3-expressing cells. Additionally, cytokine stimulation of MCEC-1 cells
      was shown to cause down-regulation of TIMP-3 expression. Knockdown of the
      metalloproteinase ADAM17, but not ADAM10 or ADAM12, gene expression reduced
      cytokine-stimulated VCAM-1 shedding. CONCLUSIONS: TIMP-3 regulates the release of
      sVCAM-1 from cytokine-stimulated endothelial cells, which is mediated by ADAM17.

PMID- 15949469
TI  - Protein kinase C epsilon mediates angiotensin II-induced activation of beta1
      integrins in cardiac fibroblasts.
AB  - OBJECTIVE: Angiotensin II (AII) promotes cardiac fibrosis by increased
      extracellular matrix production and enhanced interaction of matrix proteins with
      their cellular receptors, including integrins. AII and other growth factors
      augment beta(1)-integrin-dependent adhesion and spreading by "inside-out
      signaling" without affecting the total number of integrin receptors. "Inside-out
      signaling" involves specific signaling pathways, including protein kinase C
      (PKC), leading to activation of beta1-integrins. In the present study we
      investigated the mechanisms involved in AII-increased adhesion of adult rat
      cardiac fibroblasts (CFBs), obtained from Sprague-Dawley rats, to collagen I
      mediated by beta1-integrin. METHODS AND RESULTS: Treatment of CFBs with AII
      induced a concentration-dependent increase in adhesion to collagen I (2.2-fold,
      p<0.01) within 3-6 h of treatment. This effect was mediated by beta1-integrin via
      the angiotensin AT1 receptor and was significantly reduced by protein kinase C
      inhibition. AII significantly induced phosphorylation of PKC epsilon
      (PKCepsilon), which is involved in beta1-integrin-dependent adhesion and
      motility, and phosphorylation of the cytoplasmatic tail of beta1-integrin at
      threonine 788/789, required for adhesion. Phosphorylation of beta1-integrin and
      an increase in adhesion was also induced by l-alpha-phosphatidylinositol-3,4,5
      triphosphate (l-alpha-PIP3), an activator of endogenous PKCepsilon. AII failed to
      increase adhesion in myofibroblasts obtained from PKCepsilon (-/-) mice, but not
      in cells obtained from control mice. Co-immunoprecipitation and double
      immunofluorescence demonstrated that AII induced a close association of
      PKCepsilon with beta1-integrin in CFBs. CONCLUSION: The present study
      demonstrates that AII increased beta1-integrin-dependent adhesion to collagen I
      in cardiac fibroblasts by inside-out signaling via PKCepsilon and phosphorylation
      of the cytoplasmatic tail of the beta1-integrin.

PMID- 15949470
TI  - Kir6.2-deficient mice are susceptible to stimulated ANP secretion: K(ATP) channel
      acts as a negative feedback mechanism?
AB  - OBJECTIVE: While atrial natriuretic peptide (ANP) has been shown to be released
      mainly from cardiac muscle cells in response to atrial distension, the regulatory
      mechanisms of ANP secretion are still not fully understood. We sought to
      determine whether the ATP-sensitive K+ (K(ATP)) channel modulates the secretion
      of ANP, using mice with homozygous knockout of the Kir6.2 (a pore-forming subunit
      of cardiac K(ATP) channel) gene. METHODS: K(ATP) channel currents were recorded
      from isolated mouse atrial cells with patch-clamp techniques. Plasma ANP
      concentrations in anesthetized mice and ANP content and secretion in isolated
      atrial preparations were determined by radioimmunoassay. Action potentials were
      recorded from the isolated atria. RESULTS: Exposure to 2,4-dinitrophenol (100
      microM) evoked a glibenclamide-sensitive K(ATP) channel current in atrial cells
      from wild-type (WT) but not Kir6.2 knockout (Kir6.2 KO) mice. Although there were
      no significant differences in the basal plasma ANP levels between WT and Kir6.2
      KO mice, volume expansion caused a significant elevation of plasma ANP
      concentration in Kir6.2 KO but not WT mice with accompanying hypotension. When
      isolated left atria were stretched, ANP secreted into the bath from Kir6.2 KO
      atria was significantly higher than that from WT atria. Furthermore, stretching
      the atria from WT but not Kir6.2 KO mice significantly shortened the action
      potential duration. A hypotonic stretch of the membrane induced the glibenclamide
      sensitive K(ATP) channel current in atrial cells from WT but not Kir6.2 KO mice.
      CONCLUSIONS: Kir6.2 is essential for the function of K(ATP) channel in mouse
      atrial cells. Given that Kir6.2 KO mice are susceptible to stretch-induced
      secretion of ANP, our results suggest that K(ATP) channels may act as a negative
      feedback mechanism for the control of ANP secretion.

PMID- 15949471
TI  - Consequences of atrial electrical remodeling for the anti-arrhythmic action of
      class IC and class III drugs.
AB  - OBJECTIVE: Atrial fibrillation (AF) induces electrical and ionic remodeling of
      the atria. We investigated whether AF-induced remodeling alters the
      electrophysiological and anti-fibrillatory effects of class I (flecainide) and
      class III (d-sotalol, ibutilide) anti-arrhythmic drugs. METHODS: In 9 goats, the
      effects of flecainide (6 mg/kg) and d-sotalol (6 mg/kg) on atrial
      electrophysiology were measured both before and after 48 h of electrically
      induced AF. During a 1-h infusion period the atrial effective refractory period
      (AERP) and conduction velocity (CV) were measured both during slow and rapid
      pacing (interval 400 and 200 ms). In 8 other goats, the rate-dependent effects of
      ibutilide (0.12 mg/kg) on AERP were determined. RESULTS: The effects of
      flecainide on atrial conduction and refractoriness were not altered after 48 h of
      AF. At a dose of 6 mg/kg flecainide reduced the CV200 by 19+/-5% in normal atria
      and by 21+/-9% after 48 h of AF (p=0.20). The AERP200 was prolonged by 10+/-6%
      and 8+/-7%, respectively (p=0.40). In contrast, the effect of d-sotalol on atrial
      refractoriness was markedly diminished. During control d-sotalol prolonged the
      AERP400 by 17+/-6% compared to only 6+/-5% after 2 days of AF (p<0.01). Also
      ibutilide lost much of its class III effect on the AERP by electrical remodeling
      (from 15 to 5%; p<0.05). The loss of class III action was less pronounced at
      rapid heart rates. CONCLUSIONS: AF-induced atrial electrical remodeling in the
      goat did not modulate the action of flecainide on atrial conduction and
      refractoriness. In contrast, the class III effects of d-sotalol and ibutilide on
      the atria were strongly reduced after 2 days of AF. The prolongation of QT
      duration was not affected.

PMID- 15949472
TI  - SMAD proteins are involved in apoptosis induction in ventricular cardiomyocytes.
AB  - OBJECTIVE: The transcription factor AP-1 is a mediator of hypertrophic growth and
      apoptosis in cardiomyocytes. This puts AP-1 in the center of two important
      processes found in the failing heart and implies that variations (i) in the AP-1
      composition itself or (ii) in additional, interacting transcription factors are
      responsible for the diverse actions of AP-1. To test this hypothesis, we
      performed studies on isolated ventricular cardiomyocytes of rat under hypertrophy
      or apoptosis-inducing conditions. METHODS AND RESULTS: The NO donor SNAP (100
      microM), which is a pro-apoptotic stimulus in cardiomyocytes, activated AP-1
      within 2 h. c-Jun, JunB and FosB are identified as the main components of this AP
      1 complex. This complex formation is identical to the composition of AP-1 found
      under hypertrophic growth stimulation by phenylephrine (PE, 10 muM). Analysis of
      other transcription factors able to interact with AP-1 revealed activation of
      SMAD activity only during stimulation with SNAP to 131+/-9.6% (p < 0.05 vs.
      control, n = 9). The SMAD complex is formed from SMAD4 and 3. Intracellular
      scavenging of SMAD proteins by transformation of cardiomyocytes with SMAD decoy
      oligonucleotides or inhibition of SMAD4 synthesis using SMAD4 antisense
      oligonucleotides reduced the number of apoptotic cells under stimulation with
      SNAP from 13.3 +/- 1.2% to control levels (8 +/- 1%, p < 0.05, n = 6). TGFbeta,
      which is a known stimulator of SMAD proteins, is also shown to stimulate
      apoptosis in cardiomyocytes. Again, simultaneous activation of AP-1 and SMAD is
      needed for this apoptosis induction. CONCLUSIONS: In conclusion, AP-1/SMAD
      signaling has been identified as a common pathway in cardiomyocyte apoptosis. In
      contrast, SMAD proteins are dispensable for AP-1-mediated hypertrophic growth.
      This finding characterizes SMAD proteins as potential candidates for proteins
      that shift AP-1 signaling from hypertrophy to apoptosis.

PMID- 15949473
TI  - Additive amelioration of left ventricular remodeling and molecular alterations by
      combined aldosterone and angiotensin receptor blockade after myocardial
      infarction.
AB  - OBJECTIVES: The mechanisms underlying the clinical benefits of mineralocorticoid
      receptor antagonism in patients with left ventricular (LV) dysfunction and heart
      failure (CHF) after myocardial infarction (MI) are poorly understood. METHODS: We
      investigated whether long-term (9 weeks) aldosterone antagonism with eplerenone
      (100 mg/kg/day) provides additional benefit to angiotensin II type 1 (AT1)
      receptor inhibition with irbesartan (50 mg/kg/day) on cardiac remodeling after MI
      in rats. RESULTS: Eplerenone monotherapy, like AT1 receptor blockade,
      significantly reduced LV end-diastolic pressure (LVEDP), end-systolic volume
      (LVESV) and end-diastolic volume (LVEDV) compared to placebo. Improvement of LV
      dilation by aldosterone antagonism was associated with a significant reduction of
      increased AT1 receptor, angiotensin-converting enzyme (ACE) and endothelin-1 gene
      expression in the noninfarcted LV myocardium. Combination therapy with irbesartan
      led to a substantial further leftward shift of the LV pressure-volume curve and
      decrease in LVEDP, LVESV and LVEDV. Moreover, combination therapy significantly
      improved LV systolic and diastolic function and reversed LV alterations of alpha-
      and beta-myosin heavy-chain isoforms, ANF and SERCA2 ATPase expression more
      effectively than monotherapies. LV collagen type I and type III expression as
      well as interstitial fibrosis were substantially increased in placebo CHF rats,
      similarly decreased by eplerenone and irbesartan, and further reduced by
      eplerenone/irbesartan. However, no additive effects of eplerenone/irbesartan on
      myocardial AT1 receptor, ACE and endothelin-1 mRNAs were observed. CONCLUSIONS:
      Aldosterone receptor antagonism provides additional benefit to AT1 receptor
      blockade on LV function and remodeling associated with improvement of molecular
      alterations responsible for progressive contractile dysfunction post-MI.

PMID- 15949474
TI  - Etanercept or intravenous immunoglobulin attenuates expression of genes involved
      in post-myocardial infarction remodeling.
AB  - OBJECTIVE: Persistently elevated levels of inflammatory cytokines such as tumor
      necrosis factor (TNF)alpha after acute myocardial infarction (MI) may contribute
      to maladaptive ventricular remodeling. The aim of the present study was to
      examine the effects of immunomodulatory therapy with recombinant soluble TNF
      receptor (TNFR:Fc) or intravenous immunoglobulin (IVIg) on left and right
      ventricular post-MI remodeling in rats. METHODS AND RESULTS: Adult male Sprague
      Dawley rats were subjected to MI by left coronary artery ligation and randomized
      to treatment with vehicle, TNFR:Fc, or IVIg and sacrificed after 7 days. The main
      findings were that: (i) TNFR:Fc- and IVIg-treated rats developed less right
      ventricular (RV) hypertrophy compared to vehicle-treated controls. (ii) LV and
      arterial pressures in post-MI rats were not affected by the TNFR:Fc or IVIg
      treatment. (iii) As determined by real-time RT-PCR, both treatments reduced the
      expression of the hypertrophy-related genes, atrial natriuretic peptide and the
      ratio of beta/alpha-myosin heavy chains, and genes related to extracellular
      matrix remodeling (i.e., collagens I and III, matrix metalloproteinase [MMP]-2
      and its tissue inhibitor TIMP-1) in the non-ischemic segment of LV and, in
      particular, in the RV. (iv) Treatment with IVIg, but not TNFR:Fc, reduced MMP-2
      zymographic activity in the RV and the expression of genes for TNFalpha and
      monocyte chemoattractant protein-1. CONCLUSION: Therapy targeted directly against
      TNFalpha (i.e., TNFR:Fc) and a more general immunomodulatory approach (i.e.,
      IVIg) in the acute phase of MI attenuates the cardiac remodeling process and
      expression of genes that are involved. These findings raise the possibility that
      initiation of immunomodulatory therapy post-MI could be beneficial in preventing
      the later development of heart failure.

PMID- 15949475
TI  - Endomitosis and polyploidization of myocardial cells in the periphery of human
      acute myocardial infarction.
AB  - OBJECTIVE: Although the genetic program for reinitiating DNA synthesis exists in
      post-mitotic cardiomyocytes, and it was reported that in human acute myocardial
      infarction (AMI) a significant proportion of myocytes enter mitosis, the rule is
      that the lost tissue is replaced by a collagen scar. The purpose of this study
      was to search for the basis of this discordance in order to devise future
      strategies to induce division of myocytes into daughter cells that may replace
      the lost tissue with contractile cells. METHODS: In 15 human hearts with 1- to 21
      day-old infarcts, the expression of the cell cycle proteins Ki67 antigen, cyclins
      D, A, and B1, the presence of mitotic bodies, and the ploidy status were
      investigated with immunoenzymatic methods, light and laser confocal microscopy,
      and densitometry in the myocytes surrounding the infarct area. RESULTS: In 7- to
      13-day-old infarcts, 11.61+/-6.94% of the myocytes presented Ki67+ nuclei, and a
      lower proportion presented cyclins D, A, and B. At earlier and later times, the
      proportion of Ki67+ myocytes was significantly lower. Although under confocal
      microscopy and fluorescent labels, some of the Ki67+ myocytes appeared to be in
      different stages of mitosis, with Nomarski optics and hematoxylin
      counterstaining, the condensed chromosomes, although arranged in metaphase and
      anaphase plates or split in sister chromatids, were always located within a
      preserved nuclear envelope, indicating the presence of endomitosis. Conventional
      mitosis was exceptionally observed. In the 14- and 21-day-old infarcts, the
      ploidy of the myocytes adjacent to the infarct was significantly higher than in
      distant zones. CONCLUSION: These observations indicate that in human infarcts,
      entrance of cardiomyocytes into the cell cycle is transient and that endomitosis,
      leading to polyploidy, rather than mitosis, leading to karyokinesis, is the final
      fate of cycling cells. Both observations may account for the discordance between
      the regenerative ability of myocytes and the lack of an efficient reparative
      process in human AMI.

PMID- 15949476
TI  - Postconditioning reduces infarct size via adenosine receptor activation by
      endogenous adenosine.
AB  - OBJECTIVE: This study tested the hypothesis that brief cycles of iterative
      ischemia-reperfusion at onset of reperfusion (termed "postconditioning", post
      con) delays washout of intravascular adenosine and thereby increases endogenous
      adenosine receptor (AR) activation during the early moments of reperfusion (R).
      METHODS: Isolated mouse hearts were subjected to 20 min global ischemia (I) and
      30 min R with or without post-con (3 or 6 cycles of 10 s R&I). Intravascular
      purines in coronary effluent were analyzed by HPLC. To assess the functional role
      of endogenous AR activation in post-con, an open-chest rat model of myocardial
      infarction was employed. Rats were randomly divided into 11 groups: control, no
      intervention at R; post-con, three cycles of 10 s R followed by 10 s LCA re
      occlusion immediately upon R. In the following interventions, drugs (or vehicle)
      were administered 5 min before R in the absence or presence (+/-) of post-con.
      Vehicle (DMSO < 300 microl/kg); 8-SPT (non-selective AR antagonist, 10 mg/kg) +/-
      post-con; DPCPX (A(1A)R antagonist, 0.1 mg/kg) +/- post-con; ZM241385 (A(2A)AR
      antagonist, 0.2 mg/kg) +/- post-con; MRS1523 (A(3)AR antagonist, 2 mg/kg) +/-
      post-con. RESULTS: In isolated mouse hearts, post-con reduced diastolic pressure
      during both early (26+/-3* vs. 37+/-3 mmHg at 5 min) and late (22+/-3* vs. 34+/-3
      mmHg at 30 min) R. Post-con also hastened the early recovery of contractile
      function (developed pressure 39+/-6* vs. 16+/-2 mmHg at 5 min R), although
      differences did not persist at 30 min R. Importantly, post-con was associated
      with reduced adenosine washout (58+/-5* vs. 155+/-16 nM/min/g) at 2 min R
      suggesting greater retention time of intravascular adenosine. In rats, post-con
      significantly attenuated infarct size compared to control (40+/-3% vs. 53 +/- 2%*
      in control), an effect that was unaltered by DPCPX (42 +/- 2%) but was abrogated
      by 8-SPT (50 +/- 2%), ZM241385 (49 +/- 3%) or MRS1523 (52 +/- 1%) (P < 0.02).
      CONCLUSION: These data suggest that post-con involves endogenous activation of
      A(2A) and A3 but not A1AR subtypes. This activation may be linked to the delay in
      the washout of intravascular adenosine during the early minutes of R during which
      post-con is applied.

PMID- 15949477
TI  - Troglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 inhibit shear-induced
      coupling factor 6 release in endothelial cells.
AB  - OBJECTIVE: We previously showed that mitochondrial coupling factor 6 (CF6), an
      endogenous inhibitor of prostacyclin synthesis and a vasoconstrictor, is present
      on the surface of human umbilical vein endothelial cells (HUVEC) and is released
      outside of the cells by shear stress. We investigated the intracellular signaling
      mechanism for shear-induced release of CF6 in HUVEC and the effects of
      troglitazone and 15-deoxy-delta(12,14)-prostaglandin J2 (15d-PGJ2), both
      peroxisome proliferator-activated receptor (PPAR)-gamma ligands, on it. METHODS
      AND RESULTS: The release and gene expression of CF6 in HUVEC were enhanced by
      shear stress at 25 dyn/cm2, measured by radioimmunoassay and real-time RT-PCR,
      respectively. The intracellular content of CF6 was decreased after exposure to
      shear stress at 25 dyn/cm2. Transfection experiments with deletional and
      mutational CF6 promoter constructs, and with dominant negative mutant IkappaB
      kinase alpha (K44M) demonstrated that shear-induced CF6 transcription was
      dependent on nuclear factor-kappa B (NF-kappaB) activation. Pretreatment with
      troglitazone or 15d-PGJ2 inhibited the shear-induced release and gene expression
      of CF6, whereas fenofibric acid, a PPAR-alpha ligand, had no influence on them.
      Western blot and immunostaining showed that troglitazone and 15d-PGJ2 inhibited
      the shear-induced, reactive oxygen species (ROS)-mediated activation of NF-kappaB
      at the level of IkappaB protein. CONCLUSIONS: The shear-induced gene expression
      and release of CF6 in HUVEC are mediated by the ROS-related activation of NF
      kappaB signaling pathway. Troglitazone and 15d-PGJ2 inhibit them at the IkappaB
      protein level.

PMID- 15949478
TI  - PKC delta-induced activation of MAPK pathway is required for bFGF-stimulated
      proliferation of coronary smooth muscle cells.
AB  - OBJECTIVE: Basic fibroblast growth factor (bFGF)-stimulated proliferation of
      coronary smooth muscle cells (cSMC) contributes to the pathogenesis of
      arteriosclerosis and restenosis. However, the molecular mechanisms involved are
      not fully understood. We have shown previously that protein kinase C (PKC) and
      mitogen-activated protein kinase (MAPK) are required for the bFGF-stimulated
      mitogenic process in bovine cSMC. In this study, we determined the PKC isoform(s)
      involved and investigated their functional role in the bFGF-stimulated signaling
      and cell cycle progression in human and bovine cSMC. METHODS AND RESULTS:
      Downregulation of PKC by phorbol 12-myristate 13-acetate (PMA) inhibited bFGF
      induced DNA synthesis, the activation of MAPK, and the expression of c-myc,
      demonstrating the involvement of PMA-sensitive PKC isoforms in growth factor
      induced proliferation and the MAPK pathway. The PMA-sensitive classical PKC
      isoforms alpha, beta, gamma and novel PKC isoforms delta and epsilon were found
      in human cSMC. Whereas blocking of the classical PKC isoforms had no influence,
      the suppression of PKC delta by genetic and pharmacological approaches inhibited
      the bFGF-stimulated c-Raf1-MEK-MAPK-c-myc signaling and DNA synthesis in cSMC. In
      contrast to PKC epsilon, our results showed that bFGF activated PKC delta by
      phosphorylation in a time-dependent manner. In addition, inhibition of PKC delta
      induced a hypophosphorylation of the retinoblastoma protein and suppression of
      the cyclins D1 and A, demonstrating the importance of PKC delta for bFGF-induced
      cell cycle progression through the G1 phase in cSMC. CONCLUSIONS: Our results
      show that PKC delta is required for the bFGF-stimulated c-Raf1-MEK-MAPK-c-myc
      signaling pathway involved in the proliferation of cSMC. Therefore, it may be an
      interesting therapeutic target for preventing proliferative vascular disorders.

PMID- 15949479
TI  - HCMV infection of human vascular smooth muscle cells leads to enhanced expression
      of functionally intact PDGF beta-receptor.
AB  - BACKGROUND: Cytomegaloviruses have been shown to promote atherogenesis in animal
      models. In humans, several epidemiological and clinical studies suggest
      involvement of the human cytomegalovirus (HCMV) in the development of
      atherosclerosis. HCMV is suspected to be associated with an enhanced restenosis
      rate and the occurrence of vasculopathies after solid organ transplantation.
      However, knowledge about the cellular and molecular bases of these findings is
      very limited. METHODS AND RESULTS: Human coronary artery smooth muscle cells
      (HCASMC) were successfully infected with HCMV in vitro. Infection of HCASMC with
      all HCMV strains analyzed resulted in a substantial upregulation of the beta
      receptor of platelet-derived growth factor (PDGFR-beta) expression as
      demonstrated by immunohistochemistry, immunofluorescence, FACS, and Western blot
      analysis. The amount of PDGFR-beta protein present in HCASMC rapidly increased
      after 12 h of infection and this difference persisted for 72 h post-infection. We
      showed by quantitative FACS analysis that the extent of PDGFR-beta upregulation
      differed significantly between the HCMV strains TB40E, Toledo, and AD169. The
      expression of insulin-like growth factor receptors as well as hepatocyte growth
      factor receptors, however, was down-modulated in HCMV-infected HCASMC. Most
      importantly, the HCMV-associated upregulation of PDGFR-beta protein resulted in
      functionally intact receptors. A significantly higher increase of proliferative
      activity following stimulation with PDGF-BB was observed in HCMV-infected HCASMC
      compared to the uninfected control. CONCLUSIONS: Our data suggest that HCMV
      directly activates the PDGF system, which could promote atherogenesis and
      restenosis by activation of smooth muscle cell proliferation and neointima
      formation.

PMID- 15949480
TI  - Moderate vs. high exercise intensity: differential effects on aerobic fitness,
      cardiomyocyte contractility, and endothelial function.
AB  - OBJECTIVE: Current guidelines are controversial regarding exercise intensity in
      cardiovascular prevention and rehabilitation. Although high-intensity training
      induces larger increases in fitness and maximal oxygen uptake (VO(2max)),
      moderate intensity is often recommended as equally effective. Controlled
      preclinical studies and randomized clinical trials are required to determine
      whether regular exercise at moderate versus high intensity is more beneficial. We
      therefore assessed relative effectiveness of 10-week HIGH versus moderate (MOD)
      exercise intensity on integrative and cellular functions. METHODS: Sprague-Dawley
      rats performed treadmill running intervals at either 85%-90% (HIGH) or 65%-70%
      (MOD) of VO2max 1 h per day, 5 days per week. Weekly VO2max-testing adjusted
      exercise intensity. RESULTS: HIGH and MOD increased VO2max by 71% and 28%,
      respectively. This was paralleled by intensity-dependent cardiomyocyte
      hypertrophy, 14% and 5% in HIGH and MOD, respectively. Cardiomyocyte function
      (fractional shortening) increased by 45% and 23%, contraction rate decreased by
      43% and 39%, and relaxation rate decreased by 20% and 10%, in HIGH and MOD,
      respectively. Ca2+ transient time-courses paralleled contraction/relaxation,
      whereas Ca2+ sensitivity increased 40% and 30% in HIGH and MOD, respectively.
      Carotid artery endothelial function improved similarly with both intensities.
      EC50 for acetylcholine-induced relaxation decreased 4.3-fold in HIGH (p < 0.05)
      and 2.8-fold in MOD (p < 0.20) as compared to sedentary; difference HIGH versus
      MOD 1.5-fold (p = 0.72). Multiple regression identified rate of systolic Ca2+
      increase and diastolic myocyte relengthening as main variables associated with
      VO2max. Cell hypertrophy, contractility and vasorelaxation also correlated
      significantly with VO2max. CONCLUSIONS: The present study demonstrates that
      cardiovascular adaptations to training are intensity-dependent. A close
      correlation between VO2max, cardiomyocyte dimensions and contractile capacity
      suggests significantly higher benefit with high intensity, whereas endothelial
      function appears equivalent at moderate levels. Thus, exercise intensity emerges
      as an important variable in future preclinical and clinical investigations.

PMID- 15949481
TI  - The role and efficacy of retrograding nailing for the treatment of diaphyseal and
      distal femoral fractures: a systematic review of the literature.
AB  - The aim of this analysis has been to evaluate the efficacy of retrograde nailing
      in the treatment of distal femur and femoral shaft fractures. Articles were
      extracted from the Pubmed database and the retrieved reports were included in the
      study only if pre-specified eligibility criteria were fulfilled. Moreover, a
      constructed questionnaire was administered, aimed at assessing the quality of the
      outcomes. Twenty-four articles were eligible for the final analysis, reviewing a
      total of 914 patients (mean age of 48.8 years) who sustained 963 distal and
      diaphyseal femoral fractures. The overall mortality rate was 5.3%. The incidence
      of infection was 1.1% and for septic arthritis of the knee was 0.18%. In patients
      with distal femoral fractures, the mean time to union and rate to union were 3.4
      months and 96.9%, respectively. The mean range of knee motion was 104.6 degrees .
      The rates of knee pain, malunion and re-operations were 16.5, 5.2 and 17%,
      respectively. Patients with femoral shaft fractures had a mean time to union 3.2
      months, whilst the rate of union was 94.2%. The mean range of knee motion was
      127.6 degrees . The rates of knee pain, malunion and re-operations were 24.5, 7.4
      and 17.7%, respectively. We concluded that retrograde intramedullary nailing
      appears to be a reliable treatment option, mainly for distal femoral fractures.
      However, in the management of diaphyseal fractures, retrograde intramedullary
      nailing is associated with high rates of knee pain and lower rates of fracture
      union.

PMID- 15949482
TI  - Treatment of fracture dislocation of talus by primary tibiotalar arthrodesis
      (Blair fusion).
AB  - We present a retrospective clinical and radiological study of eight patients who
      underwent primary Blair tibiotalar arthrodesis for Hawkins' grade III fractures
      of the neck of talus. The average age of the patients was 23 years and the
      average follow-up, was 2 years. Results were good in six patients, fair in one
      and poor in one. It is concluded that the displaced talar fractures with late
      presentation are challenging to treat and Blair fusion is a reasonable procedure.

PMID- 15949483
TI  - Implant retention and removal after internal fixation of the symphysis pubis.
AB  - Although internal fixation of diastasis of the symphysis pubis is commonly
      performed, there are no clear guidelines regarding the indications for removal of
      these implants. The long-term physiologic effects of retaining these internal
      fixation devices are not well described. We surveyed the literature to assess the
      current thinking and recommendations regarding implant retention and removal.
      Twenty-four case series and two case reports were found, for a total of 482
      cases. Complications arose as a result of implant retention in 7.5% of patients,
      with infection the most common complication. There is no consensus in the
      literature regarding implant retention and removal after internal fixation of
      diastasis of the symphysis pubis.

PMID- 15949484
TI  - Functional treatment of acute metatarsal fractures: a prospective randomised
      comparison of management in a cast versus elasticated support bandage.
AB  - A randomised controlled trial was performed in 50 patients with acute isolated
      minimally displaced lesser metatarsal fractures in order to compare plaster
      immobilisation with elasticated support bandage treatment. Patients treated with
      elasticated support bandage had significantly higher AOFAS mid-foot scores at 3
      months follow-up and complained of less pain throughout the treatment period.
      There was no difference between the two groups in time to independent mobility,
      mid-foot circumference, analgesic requirements and radiological union at 3
      months. As plaster casts are associated with serious complications, which were
      encountered in these studies, we conclude that minimally displaced metatarsal
      fractures are better treated without a cast.

PMID- 15949485
TI  - Five years of ankle fractures grouped by stability.
AB  - Categories of displaced and undisplaced stable ankle fracture are well
      recognised. We report on a further group of ankle fractures which are undisplaced
      at presentation, but do not fulfil criteria for stable injuries, and therefore,
      may be at risk of displacement. The Blackburn Foot and Ankle Service operates
      evidence-based guidelines for ankle fractures, introduced in 1998. These were
      prospectively applied to 306 skeletally mature patients (308 fractures) following
      classification of the ankle fracture based upon clinical examination and
      radiography (mortise and lateral views). One hundred and forty-eight (48.4%) of
      fractures were stable, including 63 male and 85 women, median age 53 years (14
      92). Eighty-eight (28.8%) of fractures were undisplaced but potentially unstable
      based on criteria, including 53 men and 35 women, median age 42 years (14-93).
      Seventy (22.9%) of fractures were displaced, including 41 men and 29 women,
      median age 44 years (16-94). Undisplaced, unstable fractures were treated mostly
      in below-knee casts with immediate weight-bearing and follow-up radiography. Two
      fractures in this group subsequently displaced requiring fixation according to AO
      principles. The risk of displacement in potentially unstable fractures is 2.3%.
      The unstable fracture groups, whether displaced or not, were similar in age/sex
      profile.

PMID- 15949486
TI  - Predictors of functional outcome following intracapsular hip fracture in elderly
      women. A one-year prospective cohort study.
AB  - OBJECTIVES: To explore potential predictors of functional outcome one year after
      the injury in elderly women who sustained a displaced intracapsular hip fracture
      and who were treated with internal fixation, hemiarthroplasty, or total hip
      arthroplasty. PARTICIPANTS AND METHODS: Eighty-four women aged > or =50 years
      were enrolled on a consecutive basis in this one-year prospective cohort study
      reflecting standard day-to-day clinical practice. The main outcome measure was
      the rapid disability rating scale version-2 (RDRS-2) applied at hospital
      discharge and one year later. RESULTS: At hospital discharge, the total hip
      arthroplasty group was younger and had a better functional status than the
      internal fixation or hemiarthroplasty groups. One year later, the best function
      was still observed in the total arthroplasty group, but the differences were
      small and failed to achieve the level of statistical significance. During that
      one-year period, walking ability or mobility did not change significantly after
      total hip arthroplasty, but a significant proportion of the women developed
      cognitive impairment, including mental confusion, uncooperativeness, and
      depression. Overall, the most significant predictors of poor functional status
      one year after fracture were increasing age, living in an institution at time of
      injury, and poor functional status at discharge. CONCLUSIONS: In elderly women
      with a displaced intracapsular hip fracture, total hip arthroplasty is associated
      with a functional benefit within the first months after surgery. However, the
      extent to which this functional benefit is maintained over time, is less clear.
      These results support the need for randomised studies to quantify the extent to
      which, in elderly women, the early functional benefit of total hip arthroplasty
      is maintained in the long run or compromised by progressive cognitive impairment
      and other negative determinants of functional outcome.

PMID- 15949487
TI  - Reverse obliquity and transverse fractures of the trochanteric region of the
      femur; a review of 101 cases.
AB  - BACKGROUND: Reverse obliquity and transverse fractures of the proximal femur
      represent a distinct fracture pattern in which the mechanical forces displace the
      femur medially thus increasing the risk of fixation failure. There is a paucity
      of published literature in this area of trauma. This study constitutes the
      largest series of such fractures. METHODS: Using a retrospective analysis of
      prospectively collected data from a single institution, 101 reverse obliquity and
      transverse fracture patterns were identified from 3336 consecutive hip fractures.
      All surviving patients were followed up for 1 year. RESULTS: Of 100 patients
      treated operatively, 59 were treated with 135 degrees sliding hip screws (SHS),
      19 with a Medoff plates modification of the SHS, three with a sliding hip screw
      and trochanteric stabilising plate and 19 with intramedullary sliding hip screw
      devices. Nine fracture fixation-healing complications occurred, with cut-out
      being the commonest complication (seven cases). Cut-out of the implant was
      associated with femoral medialisation and a larger tip to apex distance.
      CONCLUSION: This fracture pattern is a challenge for the orthopaedic surgeon with
      a high risk of fracture healing complications. The 135 degrees SHS and the
      intramedullary devices had similar failure rates.

PMID- 15949488
TI  - Reliability of classification systems for intertrochanteric fractures of the
      proximal femur in experienced orthopaedic surgeons.
AB  - INTRODUCTION: The aim of this study was to determine the reliability of currently
      used classification systems for intertrochanteric fractures of the proximal
      femur, and to determine the reliability of these systems in experienced
      orthopaedic surgeons. MATERIALS AND METHODS: Forty intertrochanteric fractures of
      the proximal femur were classified independently by five experienced observers
      using the AO, Evans, Kyle, and Boyd classification systems on two separate
      occasions 3 months apart. The interobserver and intraobserver variation was
      assessed using kappa statistics. RESULTS: The level of agreement for
      classification into AO groups was almost perfect or substantial, and higher than
      other classification systems. When the fractures were further classified using
      the AO classification with subgroups, reliability became worse. CONCLUSIONS: The
      current study suggests that the AO classification system with groups can be used
      more reliably to measure intertrochanteric fractures of the proximal femur than
      Evans, Kyle, and Boyd classification systems. However, the reliability of the AO
      classification with subgroups is not satisfactory.

PMID- 15949489
TI  - Transverse Hoffa's or deep osteochondral fracture? An unusual fracture of the
      lateral femoral condyle in a child.

PMID- 15949490
TI  - Computerised navigation for closed reduction during femoral intramedullary
      nailing.

PMID- 15949491
TI  - An irreducible variant of intertrochanteric fractures: a technique for open
      reduction.
AB  - We report five cases of intertrochanteric fractures that needed open reduction
      after failed closed reduction techniques. In all cases the shaft fragment
      included the lesser trochanter, and there was a long spike on the head-neck
      fragment. This was evident clinically as the proximal shaft, pulled by the
      iliopsoas tendon, produced a swelling in front of the hip joint.
      Radiographically, the fracture was minimally comminuted. The anteroposterior view
      revealed upward riding of the shaft fragment, while lateral view showed the
      femoral shaft in front of the head and neck. We describe a three-step technique,
      which was applied for open reduction in these unusual cases. With the patient
      supine on a standard operating table, the fracture site was exposed. The limb was
      placed in full adduction and external rotation to slacken the iliopsoas tendon. A
      Hohmann retractor was then passed medial to the shaft and behind the fractured
      surface of the sunken femoral neck, levering it anteriorly. Traction in abduction
      and internal rotation was applied to complete the reduction. Additional iliopsoas
      tenotomy was performed in two patients. All cases were fixed with a dynamic hip
      screw and all fractures united uneventfully.

PMID- 15949493
TI  - The relation between MRI measures of inflammation and neurodegeneration in
      multiple sclerosis.
AB  - Gadolinium-enhanced magnetic resonance imaging (MRI) and measures of brain volume
      have been extensively applied in large-scale studies to assess disease activity
      and irreversible tissue damage in multiple sclerosis (MS). Although
      histopathological studies of MS demonstrated that axonal transection occurs at
      sites of inflammatory changes, the correlation between brain tissue loss and
      gadolinium enhancement was found to be either absent or poor in virtually all in
      vivo MRI studies. This review discusses the reasons of this
      "inflammation/neurodegeneration mismatch" in MS and proposes possible strategies
      for a better in vivo characterization of the complex pathological process of this
      disease.

PMID- 15949494
TI  - NG2-positive cells in CNS function and the pathological role of antibodies
      against NG2 in demyelinating diseases.
AB  - NG2 is expressed by a variety of immature glia in the CNS including
      oligodendrocyte progenitor cells, paranodal astrocytes and perisynaptic glia. The
      protein has a large extracellular domain with two LNS/Lam G domains at the N
      terminus and a short intracellular tail with a PDZ-recognition domain at the C
      terminus. Experiments suggest that the protein plays a role in migration. The PDZ
      protein GRIP was identified as an intracellular binding partner of NG2 in
      immature glial cells. A complex is formed between GRIP, NG2 and the AMPA class of
      glutamate receptors: this may position these glial receptors towards sites of
      neuronal glutamate release at synapses and during myelination. Identification of
      neuronal receptors and links to the cytoskeleton of NG2 is of critical
      importance. Some Multiple Sclerosis patients have autoantibodies to NG2 in the
      cerebral spinal fluid: such antibodies could interfere with remyelination by
      lysing oligodendrocyte progenitor cells or blocking their migration but may also
      cause pathology by disrupting glial-neuronal signalling at synapses and
      paranodes.

PMID- 15949495
TI  - Overcoming inhibitors in myelin to promote axonal regeneration.
AB  - The lack of axonal growth after injury in the adult central nervous system (CNS)
      is due to several factors including the formation of a glial scar, the absence of
      neurotrophic factors, the presence of growth-inhibitory molecules associated with
      myelin and the intrinsic growth-state of the neurons. To date, three inhibitors
      have been identified in myelin: Myelin-Associated Glycoprotein (MAG), Nogo-A, and
      Oligodendrocyte-Myelin glycoprotein (OMgp). In previous studies we reported that
      MAG inhibits axonal regeneration by high affinity interaction (K(D) 8 nM) with
      the Nogo66 receptor (NgR) and activation of a p75 neurotrophin receptor (p75NTR)
      mediated signaling pathway. Similar to other axon guidance molecules, MAG is
      bifunctional. When cultured on MAG-expressing cells, dorsal root ganglia neurons
      (DRG) older than post-natal day 4 (PND4) extend neurites 50% shorter on average
      than when cultured on control cells. In contrast, MAG promotes neurite outgrowth
      from DRG neurons from animals younger than PND4. The response switch, which is
      also seen in retinal ganglia (RGC) and Raphe nucleus neurons, is concomitant with
      a developmental decrease in the endogenous neuronal cAMP levels. We report that
      artificially increasing cAMP levels in older neurons can alter their growth-state
      and induce axonal growth in the presence of myelin-associated inhibitors.

PMID- 15949496
TI  - Intravenous immunoglobulin treatment of multiple sclerosis and its animal model,
      experimental autoimmune encephalomyelitis.
AB  - Intravenous immunoglobulin (IVIG) is an established treatment of immune-mediated
      demyelinating neuropathy. Since IVIG possesses multiple immunomodulatory and anti
      inflammatory properties, IVIG therapy may represent a way of interfering with the
      disease process in multiple sclerosis (MS). In the MS animal model experimental
      autoimmune encephalomyelitis (EAE), infusions of IVIG significantly reduced
      disease symptoms as well as the underlying CNS pathology. IVIG was only effective
      in EAE when administered in a prophylactic treatment protocol, since IVIG
      infusions during the established phase of EAE did not alter the disease course or
      the degree of inflammation found in the central nervous system. IVIG also has the
      potential to act through myelin repair mechanisms as evidenced by work done in
      the Theilers murine encephalomyelitis virus model of demyelination. Together
      these observations have led to certain expectations for IVIG as a treatment for
      MS, and have resulted in various clinical trials. Several controlled trials
      report beneficial effects of IVIG on relapse rate, new MRI lesions, and disease
      progression in relapsing-remitting MS, while a remyelinating effect of IVIG has
      not been documented. IVIG is, therefore, presently regarded as a second-line
      therapy of MS.

PMID- 15949497
TI  - Stem cell and progenitor cell transplantation in multiple sclerosis: the
      discrepancy between neurobiological attraction and clinical feasibility.
AB  - Recent developments in our understanding of stem- and progenitor cell
      differentiation raises hopes that brain damage in chronic neurological diseases
      may become repaired by systemic or focal transplantation of such cells. In this
      review the potential of such an approach is discussed, but it is also highlighted
      that many aspects regarding its feasibility or safety are currently unresolved.
      Furthermore, recent findings on the pathogenesis of multiple sclerosis lesions
      indicate that major problems in this disease rather are related to axonal
      pathology and neurodegeneration rather than to the absence of oligodendrocyte
      progenitor cells within the lesions. In light of this complex situation, it is
      concluded that clinical trials of stem- or progenitor cell transplantation in
      multiple sclerosis are currently premature.

PMID- 15949498
TI  - Mechanisms of CNS remyelination--the key to therapeutic advances.
AB  - There are two components to the treatment of multiple sclerosis (MS); the first
      is to prevent damage occurring, and the second is to repair the residual damage.
      While considerable progress has been made in the recent years with the former
      through the development of anti-inflammatory and immunomodulatory therapies,
      there are currently no effective repair therapies routinely used in MS patients.
      This represents a significant gap in the MS clinician's therapeutic armoury. In
      this article we argue that a clear understanding of the repair mechanisms
      following CNS demyelination is fundamental to filling this gap. We discuss (1)
      the cellular events involved in remyelination, (2) changes in transcription
      factor expression within oligodendrocyte precursor cells associated with their
      activation in response to demyelination, (3) the role of platelet derived growth
      factor in the OPC recruitment phase of remyelination, and (4) the significance of
      the inflammatory response associated with demyelination in creating a signalling
      environment that favours remyelination.

PMID- 15949499
TI  - Glutamate inhibition in MS: the neuroprotective properties of riluzole.
AB  - In addition to demyelination and damage to oligodendrocytes, axonal injury and
      neuronal cell death are dominating histopathological characteristics of multiple
      sclerosis (MS). Still little is known about the cause of the damage.
      Extracellular accumulation of glutamate contributes to excitotoxic injury of
      neurons and glial cells, suggesting that the maintenance of subtoxic
      extracellular glutamate levels may be crucial. Riluzole is a neuroprotective
      agent that inhibits the release of glutamate from nerve terminals and modulates
      glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in
      several experimental models of neurodegenerative disease. We performed a small
      run-in versus treatment MR-monitored pilot study in 16 primary progressive MS
      patients. The results suggest that riluzole reduces the rate of cervical cord
      atrophy and the development of T1 hypointense lesions on magnetic resonance
      imaging in primary progressive MS. The rate of brain atrophy was only slightly
      decreased. The results indicate an effect on mechanisms involving lesion
      evolution and axonal loss, but no clear effect on new lesion formation. However,
      the data suffer from several limitations and must be confirmed in future trials.

PMID- 15949500
TI  - Transplanted human bone marrow cells generate new brain cells.
AB  - Multiple studies have reported that adult cells of bone marrow origin can
      differentiate into muscle, skin, liver, lung, epithelial cells, and neurons. To
      determine whether such cells might produce neurons and other cells in the human
      brain, we examined paraffin sections from female patients who had received bone
      marrow transplants from male donors. Y-chromosomes were labeled using
      autoradiography and fluorescent in situ hybridization. Neurons and astrocytes
      were identified histologically and immunohistochemically in neocortex,
      hippocampus, striatum, and cerebellum. However, most labeled cells in both gray
      and white matter appeared to be glia. Others have suggested that such Y-labeling
      represents fusion between host and donor cells, rather than true
      transdifferentiation. The possibilities of fusion and microchimerism were
      therefore examined using buccal epithelial cells as a model system. The female
      patients in this study had received either bone marrow or stem cell (CD34+
      enriched) transplants from their brothers. Double labeling for X- and Y
      chromosomes showed that Y-labeled buccal cells could not be explained by fusion.
      Genotyping studies of one patient, her brother, and her son ruled out the
      possibility of microchimerism. Whether, and under what circumstances, some form
      of bone marrow transplantation might provide adequate number of cells capable of
      replacing lost brain cells or enhancing their function will require additional
      studies.

PMID- 15949501
TI  - Can glatiramer acetate reduce brain atrophy development in multiple sclerosis?
AB  - The assessment of brain volume changes on serial magnetic resonance imaging (MRI)
      scans can provide an objective measure of progressive atrophy reflecting the
      neurodegenerative aspects of multiple sclerosis (MS) pathology. The present
      article reviews the results of studies assessing the effect of glatiramer acetate
      (GA) treatment in preventing MS-related, MRI-measurable brain volume decrease.
      Whilst data from the extended, open-label follow-up of the US trial seem to
      indicate that long-term treatment with GA might prevent the loss of brain
      parenchyma in relapsing-remitting MS patients, longitudinal data from the
      European/Canadian MRI trial suggest that, over a short-term period of treatment,
      GA does not have a clear-cut impact on the decrease of brain volume. The effect
      of GA on MS-related brain atrophy might, therefore, be delayed and dissociated in
      time from those exerted on other clinical and MRI measures of disease activity.
      However, the modest magnitude of this effect makes it difficult to evaluate its
      impact on the actual disease progression. Further studies of adequate duration
      are now required to address this issue, as well as to confirm the sustained
      efficacy of GA treatment over long periods of follow-up.

PMID- 15949502
TI  - Protective autoimmunity and neuroprotection in inflammatory and noninflammatory
      neurodegenerative diseases.
AB  - Autoimmune diseases are traditionally viewed as an outcome of a malfunctioning of
      the immune system, in which an individual's immune system reacts against the
      body's own proteins. In multiple sclerosis (MS), a disease of the white matter of
      the central nervous system (CNS), the attack is directed against myelin proteins.
      In this article we summarize a paradigm shift proposed by us in the perception of
      autoimmune disease. Observations by our group indicating that an autoimmune
      response is the body's mechanism for coping with CNS damage led us to suggest
      that all individuals are apparently endowed with a purposeful autoimmune response
      to CNS injuries, but have only limited inherent ability to control this response
      so that its effect will be beneficial. In animals susceptible to autoimmune
      diseases, the same autoimmune T cells are responsible both for neuroprotection
      and for disease development; the timing and strength of their activity will
      determine which of these effects is expressed. Individuals with non-inflammatory
      neurodegenerative diseases need a heightened autoimmunity. We discovered that
      autoimmunity could be boosted without risk of disease induction, even in
      susceptible strains, by the use of Copolymer-1 (Copaxone(R)), a weak agonist of a
      wide range of self-reactive T cells. Here we summarize the basic findings that
      led us to formulate the concept of protective autoimmunity, the mechanisms
      underlying its constitutive presence and its on/off regulation, and its
      therapeutic implications. We also offer an explanation for the commonly observed
      presence of cells and antibodies directed against self-components in healthy
      individuals.

PMID- 15949503
TI  - Mechanisms of axonal degeneration in EAE--lessons from CNTF and MHC I knockout
      mice.
AB  - The major pathological hallmarks of multiple sclerosis (MS) comprise
      inflammation, demyelination with associated gliosis and axonal damage, which most
      likely correlates with persisting disability. Axonal damage can occur by several
      mechanisms. This article focuses on myelin disintegration and direct immune
      attack on axons by CD8-positive T-cells as two possible scenarios for axonal
      injury. As protoypic models, we investigated experimental autoimmune
      encephalomyelitis (EAE) in ciliary neurotrophic factor gene knockout mice (CNTF-/
      mice) with severe myelin pathology and EAE in beta-2 microglobulin gene knockout
      mice (beta2m-/- mice) lacking CD8-positive T-cells. The results from these
      studies indicate that the trigger attack for axonal injury even in a well-defined
      experimental design can be multi-faceted. No single factor seems to be absolutely
      necessary for the initiation of the process, but they rather act in concert and
      orchestrate tissue destruction, inflammation and regeneration. Some mechanisms of
      primary or secondary axonal damage may be shared between inflammatory and
      degenerative diseases of the nervous system, thereby establishing a link which
      might be of importance for future therapeutic strategies.

PMID- 15949504
TI  - Putative mechanisms of action of statins in multiple sclerosis--comparison to
      interferon-beta and glatiramer acetate.
AB  - Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are
      widely prescribed as cholesterol-lowering agents. They are promising candidates
      for future treatment in multiple sclerosis (MS) as they have been shown to
      exhibit immunomodulatory effects. Recent reports have demonstrated that statins
      are effective in preventing and reversing chronic and relapsing experimental
      autoimmune encephalomyelitis (EAE), an animal model of MS. Furthermore, in vitro
      experiments with human immune cells have documented an immunomodulatory mode of
      action of statins comparable to that of interferon (IFN)-beta. An open label
      clinical trial assessing simvastatin in MS revealed a significant decrease in the
      number and volume of new MRI lesions and a favourable safety profile. This
      article reviews data thus far present on the putative mechanisms of action of
      statins in the immunopathogenesis of MS. Furthermore, the role of statins as
      potential pharmacotherapy for MS is discussed in the context of the mechanisms of
      approved immunotherapies in MS, namely IFN-beta and glatiramer acetate (GA).

PMID- 15949505
TI  - Reduction of brain volume in MS. MRI and pathology findings.
AB  - Atrophy is one of the hallmarks in multiple sclerosis (MS), especially in the
      advanced stage. Modern magnetic resonance (MR) techniques can reliably measure
      brain volume and changes therein. Depending on the technique used, changes of
      about 1% may be detected. Clinicoradiological studies show good correlation
      between atrophy measures, both in brain and spinal cord, and clinical measures.
      The exact relationship between focal MS lesions and global atrophy has yet to be
      established. Number of lesions early in the disease seems to predict later
      atrophy. The exact pathomechanism of atrophy in MS probably may be explained by
      both demyelination and axonal loss--which may occur independently from each
      other.

PMID- 15949506
TI  - Magnetic resonance spectroscopy as a measure of brain damage in multiple
      sclerosis.
AB  - Recent MR studies have emphasised the importance of neuronal and axonal damage in
      multiple sclerosis. In this respect, proton MR spectroscopy (by monitoring levels
      of N-acetylaspartate, a putative marker of axonal integrity) has been
      particularly illuminating by showing indirect evidence of neurodegeneration in
      both lesional and non-lesional brain tissues from the earliest stages of the
      disease. The importance of these changes to patients' clinical disability argues
      for the primary role of neuronal pathology in the pathogenesis of the disease.

PMID- 15949507
TI  - Temporal dynamics of cerebro-cerebellar network recruitment during a cognitive
      task.
AB  - Previous investigations have demonstrated that two regions in the right
      cerebellum, one located superiorly in hemispheral lobule VI/Crus I and another
      located inferiorly in hemispheral lobule VIIB/VIIIA, are activated during verbal
      working memory performance. On the basis of functional neuroimaging patterns of
      activation, as well as known cortico-pontine and ponto-cerebellar projections,
      the superior region has been hypothesized to contribute to the articulatory
      control system of working memory whereas the inferior region has been linked to
      the phonological store. The present study used event-related fMRI and individual
      estimates of hemodynamic response for both the cerebellum and neocortex to test
      this model and characterize the task phase specific cerebro-cerebellar
      activations for a Sternberg verbal working memory task. Results demonstrated that
      the right superior cerebellum showed the strongest activation during the initial
      encoding phase of the task, and, consistent with predictions, a similar pattern
      was observed in left opercular inferior frontal and premotor regions. In
      contrast, the right inferior cerebellum exhibited the greatest activation during
      the maintenance phase of the task, and as predicted, corresponded with activation
      in the left inferior parietal lobule. The significance of the results with
      respect to cerebro-cerebellar models of verbal working memory and to theoretical
      accounts of cerebellar involvement in cognition is discussed.

PMID- 15949508
TI  - Are numbers special? The comparison systems of the human brain investigated by
      fMRI.
AB  - Many studies have suggested that the intraparietal sulcus (IPS), particularly in
      the dominant hemisphere, is crucially involved in numerical comparisons. However,
      this parietal structure has been found to be involved in other tasks that require
      spatial processing or visuospatial attention as well. fMRI was used to
      investigate three different magnitude comparisons in an event-related-block
      design: (a) Which digit is larger in numerical value (e.g., 2 or 5)? (b) Which
      digit is brighter (e.g., 3 or 3)? (c) Which digit is physically larger (e.g., 3
      or 3)? Results indicate a widespread cortical network including a bilateral
      activation of the intraparietal sulci for all different comparisons. However, by
      computing contrasts of brain activation between the respective comparison
      conditions and applying a cortical distance effect as an additional criterion,
      number-specific activation was revealed in left IPS and right temporal regions.
      These results indicate that there are both commonalities and differences in the
      spatial layout of the brain systems for numerical and physical comparisons and
      that especially the left IPS, while involved in magnitude comparison in general,
      plays a special role in number comparison.

PMID- 15949509
TI  - Time to imagine space: a chronometric exploration of representational neglect.
AB  - When describing known places from memory, patients with left spatial neglect may
      mention more right- than left-sided items, thus showing representational, or
      imaginal, neglect. This suggests that these patients cannot either build or
      explore left locations in visual mental imagery. However, in place description
      there is no guarantee that patients are really employing visual mental imagery
      abilities, rather than verbal-propositional knowledge. Thus, patients providing
      symmetrical descriptions might be using other strategies than visual mental
      imagery. To address this issue, we devised a new test which strongly encourages
      the use of visual mental imagery. Twelve participants without brain damage and 12
      right brain-damaged patients, of whom 7 had visual neglect, were invited to
      conjure up a visual mental image of the map of France. They subsequently had to
      state by pressing a left- or a right-sided key whether auditorily presented towns
      or regions were situated to the left or right of Paris on the imagined map. This
      provided measures of response time and accuracy for imagined locations. A further
      task, devised to assess response bias, used the words "left" or "right" as
      stimuli and the same keypress responses. Controls and non-neglect patients
      performed symmetrically. Neglect patients were slower for left than for right
      imagined locations. On single-case analysis, two patients with visual neglect had
      a greater response time asymmetry on the geographical task than predicted by the
      response bias task, but with symmetrical accuracy. The dissociation between
      response times and accuracy suggests that, in these patients, the left side of
      the mental map of space was not lost, but only "explored" less efficiently.

PMID- 15949510
TI  - Dynamic modulation of visual detection by auditory cues in spatial neglect.
AB  - One of the most constant findings of studies about selective attention is that
      detection of visual stimuli is enhanced when a visual cue is presented at the
      position of the upcoming target. In healthy participants, comparable benefits
      were reported when the cue was presented in a different modality than the target.
      The aim of this study was to examine spatial and temporal dynamics of visual
      attention following auditory cues in patients with spatial neglect. Twelve
      healthy subjects and five patients with left-sided neglect were asked to react to
      a small vertical line presented randomly at one of four positions. The target
      appeared 150 or 1000 ms after an auditory cue that was either static (continuous
      380 Hz tone presented to the left or right ear) or dynamic (380 Hz tone moving
      from the left to the right ear or vice versa). The reaction time pattern of
      healthy participants was unaffected by the different tones. In contrast, reaction
      times of neglect patients were significantly faster to left targets following a
      dynamic tone moving from right to left in comparison to a tone moving from left
      to right. Interestingly, static unilateral tones modulated visual attention of
      neglect patients to a lesser degree than dynamic tones. The modulation of visual
      attention by dynamic auditory cues was of short duration and disappeared after
      1000 ms. These results demonstrate a fast automatic shift of spatial attention in
      the direction of a moving tone, suggesting strong dynamic links between visual
      and auditory attention in patients with a severe spatial deficit.

PMID- 15949511
TI  - Episodic and semantic memory in mild cognitive impairment.
AB  - Little is known about episodic and semantic memory in the early predementia stage
      of Alzheimer's disease (AD), which is referred to as mild cognitive impairment
      (MCI). To explore person knowledge, item recognition and spatial associative
      memory, we designed the Face Place Test (FPT). A total of 75 subjects
      participated: 22 patients with early AD, 24 with MCI and 29 matched controls. As
      predicted, AD patients showed significant deficits in person naming, item
      recognition and recall of spatial location (placing). Surprisingly, subjects with
      MCI were also impaired on all components. There was no significant difference
      between AD and MCI except on the placing component. Analysis of the relationship
      between semantic (naming) and episodic (recognition and placing) components of
      the FPT revealed a significant association between the two episodic tasks, but
      not between episodic and semantic performance. Patients with MCI show deficits of
      episodic and semantic memory. The extent of impairment suggests dysfunction
      beyond the medial temporal lobe. The FPT might form the basis of a sensitive
      early indicator of AD.

PMID- 15949512
TI  - Writing through the phonological buffer: a case of progressive writing disorder.
AB  - A progressively dysgraphic patient is described, whose deficit involved, at
      different stages, the post-allographic, the allographic and the orthographic
      representation of words. The patient's roughly comparable difficulties in oral
      and written spelling and in dictation by composition, as the disease progressed,
      showed that the damage was no longer limited to output mechanisms but also
      involved more central processes. The nature of the errors (phonologically based),
      their identical distributions for words and non-words, the inability to write
      under articulatory suppression, the normal repetition and the impairment in
      reading and lexical decision suggest that the patient cannot rely on the
      orthographic representation of words and instead makes use of a phonological
      representation by spelling through the phonological buffer.

PMID- 15949513
TI  - Transcranial magnetic stimulation of the left human frontal eye fields eliminates
      the cost of invalid endogenous cues.
AB  - Humans are able to selectively attend to specific regions of space without moving
      their eyes. However, there is mounting evidence that these covert shifts of
      attention may employ many of the same brain regions involved when executing the
      eye movements. For example, functional magnetic resonance imaging (fMRI) studies
      show that the oculomotor region known as the frontal eye fields (FEF) are
      activated by the covert shifts of attention. However, it remains possible that
      the activations seen in these studies result from actively inhibiting eye
      movements rather than as a direct result of modulating perceptual processing.
      Here we provide direct evidence for the role of this region in endogenously
      driven spatial attention. We show that briefly disrupting the left FEFs with
      transcranial magnetic stimulation (TMS) eliminated the slow response times
      associated with the invalid strategic cues when the target appeared in the right
      visual field. At first glance, our findings appear incompatible with the results
      reported by Grosbras and Paus (Grosbras, M. -H., & Paus, T. (2002). Transcranial
      magnetic stimulation of the human frontal eye field: effects on visual perception
      and attention. Journal of Cognitive Neuroscience, 14(7), 1109--1120) and we
      suggest this is likely due to the design differences. Specifically, we disrupted
      the FEF at the time of cue onset, rather than target onset. Taken together with
      the findings of Grosbras and Paus, our findings suggest that the FEF plays an
      early role in the inhibition of perceptual information. Furthermore, our findings
      complement work by Ro et al. (Ro, T., Farne, F., & Chang, E. (2003). Inhibition
      of return and the frontal eye fields. Experimental Brain Research, 150, 290--296)
      who report that stimulation of the frontal eye fields disrupts the inhibitory
      consequences of reflexive attention shifts.

PMID- 15949514
TI  - Deviant gaze processing in children with autism: an ERP study.
AB  - This study investigated event-related potentials (ERP) during an oddball task in
      which detection of specific eye direction was required of children with and
      without autism. The detection of a change in eye direction elicited occipito
      temporal negativity, which had two major differences between children with and
      without autism. First, while this occipito-temporal negativity predominated in
      the right hemisphere of typically developed children, it was distributed equally
      bilaterally in children with autism. Second, the amplitude of this negativity was
      more pronounced in typically developed children in response to the detection of
      direct gaze as compared to averted gaze, but was not sensitive to direct/averted
      gaze direction in children with autism, which converges with behavioral reports.
      The results concur with previous literature, suggesting the importance of the
      right hemisphere, especially the superior temporal sulcus, in gaze processing.
      Results indicate that deviant neural substrates might be involved in gaze
      processing in individuals with autism.

PMID- 15949515
TI  - A split-brain model of Alzheimer's disease? Behavioral evidence for comparable
      intra and interhemispheric decline.
AB  - It has been proposed that features of Alzheimer-type dementia (AD) reflect a
      breakdown in cortical connectivity that can be likened to a disconnection
      syndrome. One hypothesized consequence of this pathology is that AD patients
      should be disproportionally impaired on measures of interhemispheric transfer.
      However, there is a paucity of studies bearing on this prediction. We report the
      results from two measures of interhemispheric interaction obtained from healthy
      younger and older adults, and older adults with probable AD. One measure examined
      speeded simple manual responses to a lateralized light flash (i.e., the
      Poffenberger task) and the other examined the interhemispheric coordination of
      computational resources using within and across hemifield variants of visual
      letter-matching tasks. AD patients show an overall impairment of performance on
      both intra and interhemispheric conditions in all tasks. However, there is no
      indication of disproportionate alteration of interhemispheric processes mediating
      either visuomotor transfer or visual letter-matching and the allocation of
      computational resources. The results, therefore, call into question the
      appropriateness of a "split-brain" model for AD, at least in the domain of visual
      processing. Although the results are not specifically diagnostic of a
      disconnection syndrome, they are consistent with the possibility of a breakdown
      of cortico-cortical connectivity both within and between the hemispheres in AD.

PMID- 15949516
TI  - Effortless control: executive attention and conscious feeling of mental effort
      are dissociable.
AB  - Recruitment of executive attention is normally associated to a subjective feeling
      of mental effort. Here we investigate the nature of this coupling in a patient
      with a left mesio-frontal cortex lesion including the anterior cingulate cortex
      (ACC), and in a group of comparison subjects using a Stroop paradigm. We show
      that in normal subjects, subjective increases in effort associated with executive
      control correlate with higher skin-conductance responses (SCRs). However, our
      patient experienced no conscious feeling of mental effort and showed no SCR, in
      spite of exhibiting normal executive control, and residual right anterior
      cingulate activity measured with event-related potentials (ERPs). Finally, this
      patient demonstrated a pattern of impaired behavior and SCRs in the Iowa gambling
      task-elaborated by Damasio, Bechara and colleagues-replicating the findings
      reported by these authors for other patients with mesio-frontal lesions. Taken
      together, these results call for a theoretical refinement by revealing a
      decoupling between conscious cognitive control and consciously reportable
      feelings. Moreover, they reveal a fundamental distinction, observed here within
      the same patient, between the cognitive operations which are depending on normal
      somatic marker processing, and those which are withstanding to impairments of
      this system.

PMID- 15949517
TI  - Recollection of vivid memories after perirhinal region stimulations:
      synchronization in the theta range of spatially distributed brain areas.
AB  - Electrical stimulation of the temporal cortex in patients with epilepsy sometimes
      elicits experiential phenomena such as recollection of vivid memories. The
      neurophysiological substrate of such phenomena is poorly understood. Furthermore,
      the relation between the site of stimulation and the type of memory elicited has
      only recently started to be investigated. We investigated these issues in patient
      FGA who had intracerebral electrodes stereotaxically implanted in the right
      temporal lobe for investigation of drug-resistant epilepsy. We report the results
      of electrical stimulations of the perirhinal region. Two stimulations elicited
      experiential phenomena consisting of visual memories that belonged to FGA's past,
      but which were not related to any particular episode. These visual memories
      consisted of objects or of details of objects. These two stimulations were
      contrasted with other stimulations in the same subhippocampal region. Cross
      correlation analysis of the depth-EEG signals filtered in frequency sub-bands
      revealed that experiential phenomena occurred only when the various brain
      structures involved in the after-discharge were synchronized in the theta range.
      These structures included the perirhinal region, the hippocampus, other limbic
      structures as well as a primary visual area. Our results suggest that
      recollection of vivid memory after electric stimulation of the cortex may rely on
      wide networks of brain areas that transiently synchronize. These results also
      highlight the role of the perirhinal region in human memory. Experiential
      phenomena are rarely obtained after brain stimulation. Replication of these
      results is thus required due to the small number of observations reported.

PMID- 15949518
TI  - Multidimensional measures of person knowledge and spatial associative learning:
      can these be applied to the differentiation of Alzheimer's disease from
      frontotemporal and vascular dementia?
AB  - Patients with early stage Alzheimer's disease (AD) show deficits in person
      knowledge and spatial associative memory. The current investigation examined the
      ability of impairment in these domains to differentiate AD from other overlapping
      conditions. In experiment 1, 14 AD patients, 21 vascular dementia (VaD) patients,
      11 frontal variant frontotemporal dementia (fvFTD) patients and 41 controls were
      administered a graded faces test. VaD patients demonstrated a level of impairment
      comparable to the AD group on both the naming and person identification elements
      of the task. A mild naming deficit was revealed in the fvFTD group. In experiment
      2, 22 AD patients, 23 patients with mild cognitive impairment (MCI), 11 fvFTD
      patients, 13 semantic dementia (SD) patients, and 23 elderly controls were
      administered the face-place test, a newly developed task that combines naming of
      famous faces, item recognition and spatial location. The naming component of the
      face-place test clearly differentiated SD patients from all dementia groups. All
      patient groups, except those with fvFTD, showed substantial deficits in the item
      recognition and spatial components. Consistency analyses indicated a fairly
      robust association between the two episodic components (item recognition and
      placing), but not between semantic and episodic elements of the FPT. Person
      knowledge deficits are, therefore, not specific to AD and the employment of face
      stimuli may influence the performance of SD patients on tasks of episodic memory.

PMID- 15949519
TI  - Imagined rotations of self versus objects: an fMRI study.
AB  - This study used functional magnetic resonance imaging (fMRI) to investigate the
      neural mechanisms underlying two types of spatial transformations: imagined
      object rotations and imagined rotations of the self about an object. Participants
      viewed depictions of single three-dimensional Shepard--Metzler objects situated
      within a sphere. A T-shaped prompt appeared outside of the sphere at different
      locations across trials. In the object rotation task, participants imagined
      rotating the object so that one of its ends was aligned with the prompt. They
      then judged whether a textured portion of the object would be visible in its new
      orientation. In the self rotation task, they imagined rotating themselves to the
      location of the T-prompt, and then judged whether a textured portion of the
      object would be visible from the new viewpoint. Activation in both tasks was
      compared to respective control conditions in which identical judgments were made
      without rotation. A direct comparison of self and object rotation tasks revealed
      activation spreading from left premotor to left primary motor (M1) cortex (areas
      6/4) for imagined object rotations, but not imagined self rotations. In contrast,
      the self rotation task activated left supplementary motor area (SMA; area 6). In
      both transformations, activation also occurred in other regions. These findings
      provide evidence for multiple spatial-transformation mechanisms within the human
      cognitive system.

PMID- 15949520
TI  - Disordered memory awareness: recollective confabulation in two cases of
      persistent deja vecu.
AB  - We describe two cases of false recognition in patients with dementia and diffuse
      temporal lobe pathology who report their memory difficulty as being one of
      persistent deja vecu--the sensation that they have lived through the present
      moment before. On a number of recognition tasks, the patients were found to have
      high levels of false positives. They also made a large number of guess responses
      but otherwise appeared metacognitively intact. Informal reports suggested that
      the episodes of deja vecu were characterised by sensations similar to those
      present when the past is recollectively experienced in normal remembering. Two
      further experiments found that both patients had high levels of recollective
      experience for items they falsely recognized. Most strikingly, they were likely
      to recollectively experience incorrectly recognised low frequency words,
      suggesting that their false recognition was not driven by familiarity processes
      or vague sensations of having encountered events and stimuli before. Importantly,
      both patients made reasonable justifications for their false recognitions both in
      the experiments and in their everyday lives and these we term 'recollective
      confabulation'. Thus, the patients are characterised by false recognition,
      overextended recollective experience, and recollective confabulation. These
      features are accounted for in terms of disrupted control of memory awareness and
      recollective states, possibly following brain damage to fronto-temporal circuits
      and we extend this account to normally and abnormally occurring states of deja vu
      and vecu and related memory experiences.

PMID- 15949521
TI  - Category specific dysnomia after thalamic infarction: a case-control study.
AB  - Category specific naming impairment was described mainly after cortical lesions.
      It is thought to result from a lesion in a specific network, reflecting the
      organization of our semantic knowledge. The deficit usually involves multiple
      semantic categories whose profile of naming deficit generally obeys the
      animate/inanimate dichotomy. Thalamic lesions cause general semantic naming
      deficit, and only rarely a category specific semantic deficit for very limited
      and highly specific categories. We performed a case-control study on a 56-year
      old right-handed man who presented with language impairment following a left
      anterior thalamic infarction. His naming ability and semantic knowledge were
      evaluated in the visual, tactile and auditory modalities for stimuli from 11
      different categories, and compared to that of five controls. In naming to visual
      stimuli the patient performed poorly (error rate>50%) in four categories:
      vegetables, toys, animals and body parts (average 70.31+/-15%). In each category
      there was a different dominating error type. He performed better in the other
      seven categories (tools, clothes, transportation, fruits, electric, furniture,
      kitchen utensils), averaging 14.28+/-9% errors. Further analysis revealed a
      dichotomy between naming in animate and inanimate categories in the visual and
      tactile modalities but not in response to auditory stimuli. Thus, a unique
      category specific profile of response and naming errors to visual and tactile,
      but not auditory stimuli was found after a left anterior thalamic infarction.
      This might reflect the role of the thalamus not only as a relay station but
      further as a central integrator of different stages of perceptual and semantic
      processing.

PMID- 15949522
TI  - Predictors of prostate cancer screening among health fair participants.
AB  - OBJECTIVES: Most previous studies of predictors for participation in prostate
      specific antigen (PSA) screening for prostate cancer have been conducted in
      purposive samples or clinical settings. This population-based study identified
      factors associated with documented PSA screening among health fair participants.
      STUDY DESIGN: Cross-sectional survey of 2098 Nebraskan men aged 35 years and
      older who participated in a health fair in central and eastern Nebraska in 1993.
      METHODS: All participants were offered a PSA screening and a questionnaire to
      collect information on demographics, family medical history, lifestyle factors
      and self-perceived health status. Predictors of PSA screening were estimated by
      odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Men were more
      likely to accept the PSA screening if they were older than 50 years of age
      (OR=3.1; 2.4-3.9), had a higher income (OR=1.5; 1.1-2.1), were currently employed
      (OR=1.4; 1.0-2.5), perceived their health status as good (OR=1.1; 0.8-1.5) or
      excellent (OR=1.4; 1.0-2.1), and believed that they themselves, rather than
      physicians, should be responsible for their health (OR=1.3; 1.0-1.7). Compared
      with men aged 50-59 years, the ORs of participation were 0.8 (0.6-1.1) for age 60
      69 years and 0.7 (0.5-1.1) for age 70+ years. Decision making was not related to
      education, marital status or body mass index. Predictors of screening remained
      unchanged when analysis was limited to men aged 50 years and over, whereas only
      high income and non-smoking status predicted participation among men younger than
      50 years of age. CONCLUSIONS: Age, income, employment status, perceived control
      of health and perceived heath status were related to participation in PSA
      screening for prostate cancer, particularly in men older than 50 years of age.
      Willingness to receive a PSA screening among men aged 50 years and over decreased
      with increasing age.

PMID- 15949523
TI  - Obesity and prostate cancer screening in the USA.
AB  - OBJECTIVE: To estimate the association between body mass index (BMI: kg/m2) and
      prostate-specific antigen (PSA) cancer screening in a nationally representative
      sample of US men aged 50 years and older using data from the 2001 Behavioral Risk
      Factor Surveillance Survey. RESPONDENTS: Men aged 50 years or older classified by
      BMI as healthy weight range (18.5-24.9), overweight (25-29.9), obese class I (30
      34.9), obese class II (35-39.9), and obese class III (> or =40). OUTCOME
      MEASURES: Interval since most recent screening for PSA. RESULTS: Adjusting for
      age, race, smoking, education, employment, income and health insurance status, we
      found that, compared with men in the healthy weight range, men in the overweight
      [odds ratio (OR)=1.13; 95% confidence interval (95% CI)=1.04-1.35], obese class I
      (OR=1.26; 95% CI=1.06-1.36) and obese class II (OR=1.14, 95% CI=1.02-1.26)
      categories were significantly more likely to have obtained a PSA test within the
      previous year. A similar pattern was observed when we examined other screening
      intervals (e.g. within past 2 years, within past 3 years, etc.). CONCLUSIONS:
      Among men aged 50 years and older, overweight and obesity is associated with
      obtaining a PSA test.

PMID- 15949524
TI  - Westernization of the nutritional pattern of Chinese children living in France.
AB  - This paper reports an analysis of dietary habits of children (aged 0-5 years)
      born to Chinese immigrant parents living in France. The nutritional investigation
      was made by face-to-face interviews with the mothers. Data were exploited using
      the general table of food composition. Chinese newborns are practically never
      breastfed (10%, compared with 55% of French babies). After 12 months of age, they
      consume a traditional diet but eat few dairy products (only once per day) and
      fresh fruits (33% never). They consume many soft drinks (85%). Daily calcium and
      vitamin C intakes are lower than the recommended intakes for preschool children.
      Dietary habits of the children of first-generation Chinese immigrants are still
      traditional in terms of the late introduction of new food and the composition of
      meals, but we observed Westernization of dietary habits such as reduced
      breastfeeding and high consumption of soft drinks.

PMID- 15949525
TI  - A health impact assessment of increased aspirin use in Wales.
AB  - AIM: To estimate the likely magnitude of health impact if all individuals at
      increased risk of cardiovascular events in Wales (total population 2.9 million)
      took low-dose aspirin. METHODS: Data from a variety of different sources were
      collected and systematically combined using simple methods and conservative
      assumptions. RESULTS: Aspirin may reduce cardiovascular mortality by 2-25% and
      avoid 330-3250 deaths per annum after allowing for a small number of fatal
      undesirable effects. COMMENT: Wales might lead the way in developing an aspirin
      programme.

PMID- 15949526
TI  - Analysis of renal service provision in south and mid Wales.
AB  - OBJECTIVES: This paper estimates point prevalence of renal replacement therapy
      (RRT) utilization within population strata defined by geography and deprivation
      in south and mid Wales. It investigates spatial accessibility of main and
      satellite renal units by comparing population and patient numbers within bands of
      travel time. STUDY DESIGN: Prevalence study based on patient registers. METHODS:
      From a list of patient and renal unit locations, geocoded at the level of unit
      postcodes, and electoral division-level denominator population data, we
      calculated RRT point prevalence for the 16 unitary authorities in the study area,
      fifths of small area deprivation, and three bands of travel time from the nearest
      main renal unit and any (main or satellite) unit. RESULTS: Overall point
      prevalence was 633 per million population (pmp) and this varied from 256 to 780
      pmp across unitary authorities. RRT prevalence was lower in more deprived areas.
      Sixty-nine percent of the population and 73% of patients lived within 30 min of a
      main renal unit. Eighty-four percent of the population and 88% of patients lived
      within 30 min of a main or satellite renal unit. CONCLUSIONS: The provision of
      satellite renal units has significantly improved spatial accessibility of RRT
      services. However, a substantial proportion of the population remains
      geographically distant from renal units. This has important implications for
      planning of future provision of RRT, given the inverse relationship between RRT
      acceptance and travel time, and the impact on quality of life of patients who
      travel frequently to renal units.

PMID- 15949527
TI  - Inequitable access to immunization and vitamin A capsule services: a case of
      ethnic minorities in three hill districts of Bangladesh.

PMID- 15949528
TI  - Aerobic batch degradation of 17-beta estradiol (E2) by activated sludge: effects
      of spiking E2 concentrations, MLVSS and temperatures.
AB  - Aerobic batch degradation of 17beta estradiol (E2) spiked into the activated
      sludge liquor from a sewage treatment plant was studied; and the likely impacts
      of E2's initial concentrations (C0), microbial population densities (MLVSS) and
      temperatures (TEMPT) were examined for a variety of combinations of these three
      factors: C0 = 10, 30 and 50 microgl(-1); MLVSS = 1750, 875 and 435 mgl(-1); and
      TEMPT = 5, 20 and 35 degrees C. The results, together with those obtained through
      two control runs performed using a killed sludge sample, demonstrated clearly
      that E2 was eliminated from the aqueous phase readily under appropriate MLVSS and
      temperature levels, with the role of sorption by biomass being less significant.
      By fitting observed concentration data with a first-order rate expression, the
      degradation rate constants (k) under all experimental conditions were estimated.
      The magnitude of k changed markedly in the range of 0.23-4.79 h(-1), following a
      general order that the higher the MLVSS was, the higher the rate constant, and
      that the higher the temperature, the higher the rate constant. An obvious
      increasing trend of the biomass-modified average rate constant (k') with
      increases in the temperature was also presented: the k' values at 5, 20 and 35
      degrees C were 0.79, 1.77 and 3.29l MLVSS g(-1)h(-1), respectively. Furthermore,
      based upon the estimated k values, the temperature coefficients (theta) over the
      ranges of 5-20 and 20-35 degrees C were determined. In similarity with the
      magnitude of theta reported for ordinary BOD-based organic matrices in domestic
      wastewater, the theta values of E2 varied in the range of 1.026-1.09, suggesting
      that the temperature impacts on the degradation rates of E2 and BOD constituents
      are probably similar.

PMID- 15949529
TI  - Radiation induced decomposition of methyl tert-butyl ether in water in presence
      of chloroform: kinetic modelling.
AB  - The destruction of methyl tert-butylether (MTBE) in water in the presence of
      chloroform has been studied using 60Co gamma irradiation. Distilled water
      solutions at three different concentrations of the individual solutes MTBE and
      CHCl3 were irradiated for various times to provide dose destruction information.
      Then, the irradiation of a mixture of MTBE (at two different concentrations) and
      CHCl3 (at one concentration) was conducted. A kinetic model was used
      incorporating recently determined bimolecular rate constants to describe the
      destruction of the MTBE and CHCl3 individually and in mixtures. These studies
      were conducted in distilled water simplifying the radiation chemistry
      significantly. With the improvements in the modelling capability, we are closer
      to being able to use the model to study "real-world" mixtures in natural waters.

PMID- 15949530
TI  - Deer antlers as a model of Mammalian regeneration.
AB  - Deer antlers are cranial appendages that develop after birth as extensions of a
      permanent protuberance (pedicle) on the frontal bone. Pedicles and antlers
      originate from a specialized region of the frontal bone; the 'antlerogeneic
      periosteum' and the systemic cue which triggers their development in the fawn is
      an increase in circulating androgen. These primary antlers are then shed and
      regenerated the following year in a larger, more complex form. Antler growth is
      extremely rapid-an adult red deer can produce a pair of antlers weighing
      approximately 30kg in three months, and involves both endochondral and
      intramembranous ossification. Since antlers are sexual secondary characteristics,
      their annual cycles of growth have evolved to be closely coordinated to the
      reproductive cycle which, in temperate species, is linked to the photoperiod.
      Cessation of antler growth and death of the overlying skin (velvet) coincides
      with a rise in circulating testosterone as the autumn breeding season approaches.
      The 'dead' antlers remain attached to the pedicle until they are shed (cast) the
      following spring when circulating testosterone levels fall. In red deer, the
      species that we study, casting of the old set of antlers is followed immediately
      by growth of the new set. Although the anatomy of antler growth and the endocrine
      changes associated with it have been well documented, the molecular mechanisms
      involved remain poorly understood. The case for continuing to decipher them
      remains compelling, despite the obvious limitations of using deer as an
      experimental model, because this research will help provide insight into why
      humans and other mammals have lost the ability to regenerate organs. From the
      information so far available, it would appear that the signaling pathways that
      control the development of skeletal elements are recapitulated in regenerating
      antlers. This apparent lack of any specific 'antlerogenic molecular machinery'
      suggests that the secret of deers' ability to regenerate antlers lies in the
      particular cues to which multipotential progenitor/stem cells in an antler's
      'regeneration territory' are exposed. This in turn suggests that with appropriate
      manipulation of the environment, pluripotential cells in other adult mammalian
      tissues could be stimulated to increase the healing capacity of organs, even if
      not to regenerate them completely. The need for replacement organs in humans is
      substantial. The benefits of increasing individuals' own capacity for
      regeneration and repair are self evident.

PMID- 15949531
TI  - The molecular and genetic control of leaf senescence and longevity in
      Arabidopsis.
AB  - The life of a leaf initiated from a leaf primordium ends with senescence, the
      final step of leaf development. Leaf senescence is a developmentally programmed
      degeneration process that is controlled by multiple developmental and
      environmental signals. It is a highly regulated and complex process that involves
      orderly, sequential changes in cellular physiology, biochemistry, and gene
      expression. Elucidating molecular mechanisms underlying such a complex, yet
      delicate process of leaf senescence is a challenging and important biological
      task. For the past decade, impressive progress has been achieved on the molecular
      processes of leaf senescence through identification of genes that show enhanced
      expression during senescence. In addition, Arabidopsis has been established as a
      model plant for genetic analysis of leaf senescence. The progress on the
      characterization of genetic mutants of leaf senescence in Arabidopsis has firmly
      shown that leaf senescence is a genetically controlled developmental phenomenon
      involving numerous regulatory elements. Especially, employment of global
      expression analysis as well as genomic resources in Arabidopsis has been very
      fruitful in revealing the molecular genetic nature and mechanisms underlying leaf
      senescence. This progress, including molecular characterization of some of the
      genetic regulatory elements, are revealing that senescence is composed of a
      complex regulatory network. In this review, we will present current understanding
      of the molecular genetic mechanisms by which leaf senescence is regulated and
      processed, focusing mostly on the regulatory factors of senescence in
      Arabidopsis. We also present a potential biotechnological implication of leaf
      senescence studies on the improvement of important agronomic traits such as crop
      yield and post-harvest shelf life. We further provide future research prospects
      to better understand the complex regulatory network of senescence.

PMID- 15949532
TI  - Cripto-1: an oncofetal gene with many faces.
AB  - Human Cripto-1 (CR-1), a member of the epidermal growth factor (EGF)-CFC family,
      has been implicated in embryogenesis and in carcinogenesis. During early
      vertebrate development, CR-1 functions as a co-receptor for Nodal, a transforming
      growth factor beta (TGFbeta) family member and is essential for mesoderm and
      endoderm formation and anterior-posterior and left-right axis establishment. In
      adult tissues, CR-1 is expressed at a low level in all stages of mammary gland
      development and expression increases during pregnancy and lactation.
      Overexpression of CR-1 in mouse mammary epithelial cells leads to their
      transformation in vitro and, when injected into mammary glands, produces ductal
      hyperplasias. CR-1 can also enhance migration, invasion, branching morphogenesis
      and epithelial to mesenchymal transition (EMT) of several mouse mammary
      epithelial cell lines. Furthermore, transgenic mouse studies have shown that
      overexpression of a human CR-1 transgene in the mammary gland under the
      transcriptional control of the mouse mammary tumor virus (MMTV) promoter results
      in mammary hyperplasias and papillary adenocarcinomas. Finally, CR-1 is expressed
      at high levels in approximately 50 to 80% of different types of human carcinomas,
      including breast, cervix, colon, stomach, pancreas, lung, ovary, and testis. In
      conclusion, EGF-CFC proteins play dual roles as embryonic pattern formation genes
      and as oncogenes. While during embryogenesis EGF-CFC proteins perform specific
      and regulatory functions related to cell and tissue patterning, inappropriate
      expression of these molecules in adult tissues can lead to cellular proliferation
      and transformation and therefore may be important in the etiology and/or
      progression of cancer.

PMID- 15949533
TI  - Programmed cell death in plant embryogenesis.
AB  - Successful embryonic development in plants, as in animals, requires a strict
      coordination of cell proliferation, cell differentiation, and cell-death
      programs. The role of cell death is especially critical for the establishment of
      polarity at early stages of plant embryogenesis, when the differentiation of the
      temporary structure, the suspensor, is followed by its programmed elimination.
      Here, we review the emerging knowledge of this and other functions of programmed
      cell death during plant embryogenesis, as revealed by developmental analyses of
      Arabidopsis embryo-specific mutants and gymnosperm (spruce and pine) model
      embryonic systems. Cell biological studies in these model systems have helped to
      identify and order the cellular processes occurring during self-destruction of
      the embryonic cells. While metazoan embryos can recruit both apoptotic and
      autophagic cell deaths, the ultimate choice depending on the developmental task
      and conditions, plant embryos use autophagic cell disassembly as a single
      universal cell-death pathway. Dysregulation of this pathway leads to aberrant or
      arrested embryo development. We address the role of distinct cellular components
      in the execution of the autophagic cell death, and outline an overall mechanistic
      view of how cells are eliminated during plant embryonic pattern formation.
      Finally, we discuss the possible roles of some of the candidate plant cell-death
      proteins in the regulation of developmental cell death.

PMID- 15949534
TI  - Physiological roles of aquaporins in the choroid plexus.
AB  - The choroid plexus is a specialized tissue that lines subdomains within the four
      ventricles of the brain where most of the cerebrospinal fluid is produced.
      Maintenance of an equilibrium in volume and composition of the cerebrospinal
      fluid (CSF) is vital for a normal brain function, ensuring an optimal environment
      for the neurons. The necessarily high water permeability of the choroid plexus
      barrier is made possible by the abundant expression of a water channel, Aquaporin
      1 (AQP1), on the apical side of the membrane from early stages of development
      through adulthood. Data from studies of AQP1 suggest that it also can contribute
      as a gated ion channel, and suggest that the AQP1-mediated ionic conductance has
      physiological significance for the regulation of cerebrospinal fluid secretion.
      The regulation of AQP1 ion channels could be one of several transport mechanisms
      that contribute to the decreased CSF secretion in response to endogenous
      signaling molecules such as atrial natriuretic peptide. Numerous classes of ion
      channels and transporters are targeted specifically to each side of the cellular
      membrane, and they all work in concert to secrete CSF. Several signaling cascades
      have a direct effect on transporters and ion channels present in the choroid
      plexus epithelium, altering their transport activity and therefore modulating the
      net transcellular movement of solutes and water. Several neurotransmitters,
      neuropeptides, and growth factors can influence CSF secretion by direct effect on
      transport mechanisms of the epithelium. The mammalian choroid plexus receives
      innervation from noradrenergic sympathetic fibers, cholinergic and peptidergic
      fibers that modulate CSF secretion. Water imbalance in the brain can have life
      threatening consequences resulting from altered excitability and
      neurodegeneration, disruption of the supply of nutrients, loss of signaling
      molecules, and the accumulation of unwanted toxins and metabolites. Understanding
      the mechanisms involved in the modulation of CSF secretion is of fundamental
      importance. An appreciation of AQP1 as an ion channel in addition to its role as
      a water channel should offer new targets for therapeutic strategies in diseases
      involving water imbalance in the brain.

PMID- 15949535
TI  - Control of food intake through regulation of cAMP.
AB  - The 3', 5'-cyclic adenosine monophosphate (cAMP) is a classic second messenger
      that is intimately involved in the regulation of food intake at the hypothalamus.
      cAMP can mediate the orexigenic and anorectic effects of various peripheral
      hormones or neuropeptides in a region-specific and neuron-specific manner. The
      importance of cAMP is particularly highlighted in a series of findings about cAMP
      transducing the anorectic signals of leptin and alpha-msh. This chapter provides
      an overview of several studies on how regulation of food intake takes place with
      cAMP as the second messenger in the hypothalamus.

PMID- 15949536
TI  - Factors affecting male song evolution in Drosophila montana.
AB  - D. montana (a species of the D. virilis group) has spread over the northern
      hemisphere, populations from different areas showing both genetic and phenotypic
      divergence. The males of this species produce an elaborate courtship song, which
      plays a major role both in species recognition and in intraspecific mate choice.
      The genetic architecture and physical constraints, as well as the importance of
      the signal for species recognition, set boundaries within which this signal can
      vary. Within these limits, courtship song parameters may change, depending on the
      males' physical condition and on the environment they inhabit. Females are likely
      to affect song evolution by exerting directional selection toward higher carrier
      frequencies. Given this complexity, only a comprehensive, multidisciplinary
      approach, starting with traditional field observation and combining controlled
      behavioral experiments, biometric measurements, and sophisticated molecular
      techniques, has the potential of shedding light on the past history and the
      evolution of this signal, and, eventually, adding to our understanding of the
      mechanisms, functions, and outcomes of sexual selection in acoustic communication
      systems.

PMID- 15949537
TI  - Prostanoids and phosphodiesterase inhibitors in experimental pulmonary
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease with a poor
      prognosis, characterized by intimal lesions, medial hypertrophy, and adventitial
      thickening of precapillary pulmonary arteries. Several approved therapies are
      currently available for the treatment of PAH, of which intravenous epoprostenol
      is the best explored over the past decade. Newly available oral endothelin
      receptor antagonists, although clinically efficacious, bear the risk of liver
      toxicity in a significant portion of patients. Substances that stimulate the
      formation of the second messengers cyclic adenosine monophosphate (cAMP) or
      guanosine monophosphate (cGMP) have proved useful in the treatment of various
      forms of pre-capillary pulmonary hypertension. These second messengers of the
      endogenous vasodilator mediators that include prostacyclin and nitric oxide (NO)
      are hydrolyzed by cyclic nucleotide phosphodiesterases (PDEs), a class of enzymes
      from which 11 isoforms have been characterized. This chapter highlights
      developments in the treatment of experimental pulmonary hypertension with special
      attention to prostanoids and PDE inhibitors. We summarize findings for the acute
      vasodilatory as well as chronic effects of prostanoids, PDE inhibitors, or
      combinations of both, in animal models of pulmonary hypertension.

PMID- 15949538
TI  - 14-3-3 protein signaling in development and growth factor responses.
AB  - Tyrosine and serine phosphorylation are central to cellular signaling in growth
      and development. 14-3-3 proteins function as dimeric phosphoserine-binding
      proteins with documented interactions throughout the eukaryotic proteome and are
      highly conserved in both the animal and plant kingdoms. Binding of 14-3-3 to a
      client protein can have a range of context-dependent effects, including
      conformational change, enzyme inhibition, a shielding effect, re-localization,
      and bridging between two molecules. Proteome-based strategies utilizing mass
      spectrometry have revealed an unprecedented central stage for 14-3-3 in signal
      transduction with interacting partners composing at least 0.6% of the cellular
      proteome. 14-3-3 has been shown to bind to the human GM-CSF, IL-3, and IL-5
      receptors and is required for the transmission of cell survival. 14-3-3 is
      involved in survival-specific signals, acting not only at the receptor level but
      also at critical steps downstream of the receptor. This phosphoserine-mediated
      pathway works independently of tyrosine kinases, highlighting an alternative
      mechanism of signaling for this receptor family. Other growth factor receptors
      and their adaptors are also being shown to associate with 14-3-3 and/or have
      putative 14-3-3 interaction sequences, such as the prolactin receptor, IGF-1
      receptor, and some G-protein coupled receptors. 14-3-3 proteins are remarkably
      conserved through eukaryotic organisms and in Drosophila are required for
      photoreceptor development, learning, timing of cell cycles, and maintenance of
      cellular polarity. These findings are elevating our initial description of
      biochemical interactions to a better understanding of 14-3-3 function at the
      level of the whole organism. Further study should explore the integration of
      phosphoserine and phosphotyrosine signaling by 14-3-3 proteins and the role of
      isoform-specific functions in higher organisms. The prevalence of functional 14-3
      3 binding sites throughout the proteome, and especially among growth factor
      receptors and signaling molecules, reflects a global role for 14-3-3 in multiple
      cellular decision making.

PMID- 15949539
TI  - Skeletal stem cells in regenerative medicine.
AB  - Postnatal stem cells have been isolated from a variety of tissues and they are
      highly expected to have potentiality to be utilized for cell-based clinical
      therapies. Bone marrow stromal stem cells (BMSSCs) derived from bone marrow
      stromal tissue have been identified as a population of multipotent mesenchymal
      stem cells that are capable of differentiating into osteoblasts, adipocytes,
      chondrocytes, muscle cells, and neural cells. The most significant tissue
      regeneration trait of BMSSCs is their in vivo bone regeneration capability, which
      has been widely studied for understanding molecular and cellular mechanisms of
      osteogenesis, and, more importantly, developing into a stem-cell-based therapy.
      Recent studies further demonstrated that BMSSC-mediated bone regeneration is a
      promising approach for regenerative medicine in clinical trials. However, there
      are some fundamental questions that remain to be answered prior to successful
      utilization of BMSSCs in clinical therapy. For instance, how to maintain stemness
      of BMSSCs will be a critical issue for developing methodologies to propagate
      multi-potential stem cells in vitro, in order to allow the development of
      effective clinical therapies.

PMID- 15949540
TI  - "Roadblocks" revisited: neural change, stuttering treatment, and recovery from
      stuttering.
AB  - In light of emerging findings concerning untreated recovery and neural
      plasticity, this paper re-examines the viability of an NIH conference
      recommendation [Cooper, J. A. (1990). Research directions in stuttering:
      Consensus and conflict. In Cooper, J. A. (Ed.), Research needs in stuttering:
      Roadblocks and future directions (pp. 98-100). Rockville, MD: American Speech
      Language-Hearing Association.] that adults who have recovered from stuttering
      might inform our understanding of the nature and treatment of persistent
      stuttering. It is suggested that those who have recovered could constitute a
      behavioral, cognitive, and neurophysiologic benchmark for evaluating stuttering
      treatment for adolescents and adults, while helping to identify the limits of
      recovery from a persistent disorder. This possibility seems especially promising
      because of findings from recent studies investigating untreated recovery during
      childhood and adulthood, the emerging evidence concerning neural plasticity and
      reorganization, and reports of neural system changes during stuttering treatment.
      Potential obstacles to applying findings from unassisted recovery to treatment do
      exist, but the benefits of attempts to fully understand stuttering certainly
      outweigh the difficulties. EDUCATIONAL OBJECTIVES: After completing this
      activity, the learner will be able to: (1) describe two complexities involved in
      determining whether recovery from stuttering was assisted or unassisted; (2)
      discuss the implications for stuttering research of two neural plasticity
      research findings from areas other than stuttering; and (3) evaluate the possible
      implications for stuttering treatment of a coordinated research program that
      addresses behavioral, cognitive, and neurological characteristics of assisted and
      unassisted recovery from stuttering.

PMID- 15949541
TI  - Phonological neighborhood density in the picture naming of young children who
      stutter: preliminary study.
AB  - The purpose of this study was to assess the effect of phonological neighborhood
      density on the speech reaction time (SRT) and errors of children who do and do
      not stutter during a picture-naming task. Participants were nine 3-5-year-old
      children who stutter (CWS) matched in age and gender to nine children who do not
      stutter (CWNS). Initial analyses indicated that both CWNS and CWS were
      significantly faster (i.e., exhibited shorter SRTs) and more accurate on
      phonologically sparse than phonologically dense words, findings consistent with
      those found with older children (Newman & German, 2002). Further analyses
      indicated that talker group differences in receptive language scores weakened
      these findings. These preliminary findings were taken to suggest that
      phonological neighborhood density appears to influence the picture-naming speed
      and accuracy of preschool-aged children. EDUCATIONAL OBJECTIVES: The reader will
      learn about and be able to: (1) recognize the relevance of examining phonological
      variables in relation to childhood stuttering; and (2) describe the method of
      measuring speech reaction times and errors during a picture-naming task as a
      means of assessing linguistic skills.

PMID- 15949542
TI  - The anti-oxidative properties of alpha-tocopherol in gamma-irradiated UHMWPE with
      respect to fatigue and oxidation resistance.
AB  - Although addition of an antioxidant (alpha-tocopherol) is reported to prevent
      delamination in ultrahigh molecular weight polyethylene (UHMWPE) knee components,
      contribution of alpha-tocopherol as an antioxidant to the improvement of long
      term fatigue performance of UHMWPE is an unknown mechanism. To solve this
      problem, bi-directional sliding fatigue tests were performed for gamma-irradiated
      (25 kGy), gamma-irradiated (25 kGy) with 0.3 wt% alpha-tocopherol added, and
      gamma-irradiated (25 kGy) with 0.3 wt% tocopheryl acetate added UHMWPE specimens.
      Internal defect initiation was quantified with scanning acoustic tomography
      (SAT). Also, oxidation index and crystallinity were obtained from infrared
      absorption spectra measured using Fourier transform infrared (FT-IR) microscopy.
      Only gamma-irradiated UHMWPE specimens resulted in severe fatigue fractures.
      alpha-Tocopherol-added UHMWPE specimens showed significantly lower projected area
      ratio of defects (1.80+/-0.82) than did gamma-irradiated (7.0+/-2.29) and
      tocopheryl acetate-added ones (8.50+/-2.01). The oxidation index of gamma
      irradiated UHMWPE specimens (0.111+/-0.0052) was extremely higher compared to
      those of doped ones; 0.0179+/-0.0026 and 0.0144+/-0.0069 for alpha-tocopherol
      added and tocopheryl acetate-added ones, respectively. The crystallinity of gamma
      irradiated UHMWPE specimens (57.5+/-1.16) was lower compared to those of doped
      ones; 60.3+/-0.72 and 60.4+/-1.38 for alpha-tocopherol-added and tocopheryl
      acetate-added ones, respectively. The incorporation of alpha-tocopherol
      significantly improves the long-term fatigue performance of gamma-irradiated
      UHMWPE with oxidation stability. Also, the addition of alpha-tocopherol controls
      macromolecular structures resulting in the improvement of fatigue performance of
      UHMWPE.

PMID- 15949543
TI  - Cyclic silicate active site and stereochemical match for apatite nucleation on
      pseudowollastonite bioceramic-bone interfaces.
AB  - Hydroxyapatite (Ca5(PO4)3(OH)) forms on pseudowollastonite (psW) (alpha-CaSiO3)
      in vitro in simulated body fluid, human parotid saliva and cell-culture medium,
      and in vivo in implanted rat tibias. We used crystallographic constraints with ab
      initio molecular orbital calculations to identify the active site and reaction
      mechanism for heterogeneous nucleation of the earliest calcium phosphate
      oligomer/phase. The active site is the planar, cyclic, silicate trimer (Si3O9) on
      the (001) face of psW. The trimer has three silanol groups (>SiOH) arranged at 60
      degrees from each other, providing a stereochemical match for O atoms bonded to
      Ca2+ on the (001) face of hydroxyapatite. Calcium phosphate nucleation is modeled
      in steps as hydrolysis of surface Ca-O bonds with leaching of Ca2+ into solution,
      protonation of the surface Si-O groups to form silanols, calcium sorption as an
      inner-sphere surface complex and, attachment of HPO4(2-). Our model explains the
      experimental solution and high resolution transmission electron microscopy data
      for epitaxial hydroxyapatite growth on psW in vitro and in vivo. We propose that
      the cyclic silicate trimer is the universal active site for heterogeneous,
      stereochemically promoted nucleation on silicate-based bioactive ceramics. A
      critical active site-density and a point of zero charge of the bioceramic less
      than physiological pH are required for bioactivity.

PMID- 15949544
TI  - The effect of crystallinity on the deformation mechanism and bulk mechanical
      properties of PLLA.
AB  - Poly (l-lactide) is a widely studied biomaterial, currently approved for use in a
      range of medical devices, however, most in vitro studies have so far focussed
      upon either the bulk properties during degradation and/or deformation, or on the
      microstructure of the unloaded material during degradation. This study aimed to
      combine these approaches through the technique of simultaneous small-angle X-ray
      scattering and tensile testing at various stages of degradation up to 8 months,
      on material with a range of induced microstructures. Results showed that the
      amorphous material deformed by crazing in the dry, wet and degraded states,
      however, the mechanism by which the craze developed changed significantly on
      hydration. Despite this difference, there was little change in the bulk
      mechanical properties. Crystalline materials deformed through crystal-mediated
      deformation, with contributions from both cavitation and fibrillated shear, but
      surprisingly, differences in the length scales within the spherulitic structure
      caused by annealing at different temperatures had very little effect on the
      mechanism of deformation, though differences were seen in the bulk properties.
      Furthermore, hydration had little effect on the crystalline materials, though
      degradation over 8 months resulted in loss of mechanical properties for samples
      produced at higher annealing temperatures. In conclusion, the introduction of
      crystallinity had a huge effect on both bulk and microscopic properties of PLLA,
      but the spherulitic structure of the crystalline material affected the bulk
      properties significantly more than it did the micromechanism of deformation.

PMID- 15949545
TI  - Morphological characterization and in vitro biocompatibility of a porous nickel
      titanium alloy.
AB  - Disks consisting of macroporous nickel-titanium alloy (NiTi, Nitinol, Actipore)
      are used as implants in clinical surgery, e.g. for fixation of spinal
      dysfunctions. The morphological properties were studied by scanning electron
      microscopy (SEM) and by synchrotron radiation-based microtomography (SRmuCT). The
      composition was studied by X-ray diffractometry (XRD), differential scanning
      calorimetry (DSC), and energy-dispersive X-ray spectroscopy (EDX). The mechanical
      properties were studied with temperature-dependent dynamical mechanical analysis
      (DMA). Studies on the biocompatibility were performed by co-incubation of porous
      NiTi samples with isolated peripheral blood leukocyte fractions
      (polymorphonuclear neutrophil granulocytes, PMN; peripheral blood mononuclear
      leukocytes, PBMC) in comparison with control cultures without NiTi samples. The
      cell adherence to the NiTi surface was analyzed by fluorescence microscopy and
      scanning electron microscopy. The activation of adherent leukocytes was analyzed
      by measurement of the released cytokines using enzyme-linked immunosorbent assay
      (ELISA). The cytokine response of PMN (analyzed by the release of IL-1ra and IL
      8) was not significantly different between cell cultures with or without NiTi.
      There was a significant increase in the release of IL-1ra (p<0.001), IL-6
      (p<0.05), and IL-8 (p<0.05) from PBMC in the presence of NiTi samples. In
      contrast, the release of TNF-alpha by PBMC was not significantly elevated in the
      presence of NiTi. IL-2 was released from PBMC only in the range of the lower
      detection limit in all cell cultures. The material, clearly macroporous with an
      interconnecting porosity, consists of NiTi (martensite; monoclinic, and
      austenite; cubic) with small impurities of NiTi2 and possibly NiC(x). The
      material is not superelastic upon manual compression and shows a good
      biocompatibility.

PMID- 15949546
TI  - Morphological and topographic effects on calcification tendency of pHEMA
      hydrogels.
AB  - Poly(2-hydroxyethyl methacrylate) hydrogels were prepared in the presence of
      varying concentrations of water, or a co-monomer ethoxyethyl methacrylate at
      different strengths of crosslinking agent ethylene glycol dimethacrylate.
      Calcification tendency and its correlation with monomer mixture composition,
      topography and porosity of these materials were investigated. Scanning (SEM) and
      transmission electron microscopy (TEM) was used to study topography and porosity
      respectively. Calcification and calcium diffusion ability in to the hydrogels
      were investigated by light microscopy, SEM and energy dispersive analysis of X
      rays (EDAX) after incubation of the materials in a metastable calcifying solution
      for 48 days. Polymer and solvent volume fractions were also studied to determine
      if a correlation existed between porosity and calcification. Most of the series
      of hydrogels showed surface irregularities. Internal structure showed evidence of
      a porous structure in one of the series. Calcification studies indicated
      diffusion of calcium ions in some of the series. The diffusion of calcium is
      limited to 30-40 microm in most calcified specimens. For hydrogels that exhibited
      substantial surface irregularities and micro channels, the infiltration of
      calcium up to 200 microm was observed. Attempts to detect porosity by electron
      microscopy failed in some of the hydrogels due to difficulty in sample processing
      and sectioning. However, collaboration of the results with different techniques
      used, indicated that surface defects are the major contributors to calcium
      deposition. Decrease in porosity reduces the amount of calcium deposits and
      infiltration with decreasing solvent volume fraction which is associated with
      crosslinking concentration and initial water content of the polymer.

PMID- 15949547
TI  - The effects of particle size and surface coating on the cytotoxicity of nickel
      ferrite.
AB  - The safety and toxicity of nanoparticles are of growing concern despite their
      significant scientific interests and promising potentials in many applications.
      The properties of nanoparticles depend not only on the size but also the
      structure, microstructure and surface coating. These in turn are controlled by
      the synthesis and processing conditions. The dependence of cytotoxicity on
      particle size and on the presence of oleic acid as surfactant on nickel ferrite
      particles were investigated in vitro using the Neuro-2A cell line as a model. For
      nickel ferrite particles without oleic acid prepared by ball milling,
      cytotoxicity was independent of particle size within the given mass
      concentrations and surface areas accessible to the cells. For nickel ferrite
      particles coated with oleic acid prepared by the polyol method, the cytotoxicity
      significantly increased when one or two layers of oleic acid were deposited.
      Large particles (150+/-50 nm diameter) showed a higher cytotoxicity than smaller
      particles (10+/-3 nm diameter).

PMID- 15949548
TI  - Transitory oxidative stress in L929 fibroblasts cultured on poly(epsilon
      caprolactone) films.
AB  - Poly(epsilon-caprolactone) (PCL) is considered as a potential substrate for wide
      medical applications. In previous studies we carried out the in vitro
      biocompatibility assessment of PCL films using L929 mouse fibroblasts, obtaining
      good cell behaviour but a transitory stimulation of mitochondrial activity and
      cell retraction. Reactive oxygen species (ROS), mainly formed in mitochondria,
      can impair the function of several cellular components and produce cell oxidative
      stress by changing the normal red-ox status of the major cell antioxidants as
      glutathione. The aim of this study was to measure intracellular ROS production
      and glutathione content of L929 fibroblasts cultured on PCL films. Cell size,
      internal complexity, cell cycle and lactate dehydrogenase release were also
      evaluated. The films were treated with NaOH before culture to improve the cell
      polymer interaction. PCL induces a transitory but significant oxidative stress in
      L929 fibroblasts. The treatment of PCL films with NaOH reduces this effect. PCL
      also induces transitory changes on cell size and complexity. Nevertheless, after
      7 days in culture, cells reach control levels for all the studied parameters.
      Neither cell cycle nor membrane integrity appears affected by this oxidative
      stress respect to control cells at any culture time. These results underline the
      cytocompatibility of PCL films and, therefore, its potential utility as a
      suitable scaffold in tissue engineering.

PMID- 15949549
TI  - The role of osteopontin in foreign body giant cell formation.
AB  - Foreign body giant cells (FBGCs) are a hallmark of the foreign body reaction
      caused by biomaterial implantation and are thought to contribute to biomaterial
      degradation and the duration of the response. Osteopontin (OPN) is a secreted,
      acidic matricellular protein with multiple phosphorylation sites that is highly
      expressed at sites of inflammation. OPN wildtype and knockout mice were implanted
      with poly(vinyl alcohol) sponges and explanted at 14 days. OPN knockout mice had
      more foreign body giant cells but fewer macrophages surrounding the implants than
      their wildtype counterparts. In an in vitro human FBGC assay, addition of soluble
      OPN was found to reduce macrophage fusion to giant cells. These are the first
      studies to show a direct inhibitory role of OPN in FBGC formation in response to
      implantation.

PMID- 15949550
TI  - The biocompatibility of dibutyryl chitin in the context of wound dressings.
AB  - Dibutyryl chitin (DBC) is a modified chitin carrying butyryl groups at 3 and 6
      positions; its peculiarity is that it dissolves promptly in common solvents,
      while being insoluble in aqueous systems. The high biocompatibility of dibutyryl
      chitin in the form of films and non-wovens has been demonstrated for human, chick
      and mouse fibroblasts by the Viability/Cytotoxicity assay, In situ Cell
      Proliferation assay, Neutral Red Retention assay, Lactate Dehydrogenase Release
      assay, MTS cytotoxicity assay, and scanning electron microscopy. DBC was hardly
      degradable by lysozyme, amylase, collagenase, pectinase and cellulase over the
      observation period of 48 days at room temperature, during which no more than
      1.33% by weight of the DBC filaments (0.3 mm diameter) was released to the
      aqueous medium. DBC non-wovens were incorporated into 5-methylpyrrolidinone
      chitosan solution and submitted to freeze-drying to produce a reinforced wound
      dressing material. The latter was tested in vivo in full thickness wounds in
      rats. The insertion of 4x4 mm pieces did not promote any adverse effect on the
      healing process, as shown histologically. DBC is therefore suitable for
      contacting intact and wounded human tissues.

PMID- 15949551
TI  - Adipose tissue engineering using mesenchymal stem cells attached to injectable
      PLGA spheres.
AB  - The reconstruction of soft tissue defects remains a challenge in plastic and
      reconstructive surgery, and a real clinical need exists for an adequate solution.
      This study was undertaken in order to differentiate mesenchymal stem cells (MSCs)
      into adipocytes, and to then assess the possibility of constructing adipose
      tissue via the attachment of MSCs to injectable PLGA spheres. We also designed
      injectable PLGA spheres for scar-free transplantation. In this study, MSCs and
      adipo-MSCs (MSCs cultured in adipogenic medium for 7 days) were attached to PLGA
      spheres and cultured for 7 days, followed by injection into nude mice for 2
      weeks. As a result, the difference between lipid accumulation in adipo-MSCs at 1
      and 7 days was much higher in vitro than in the MSCs. Two weeks after injection,
      a massive amount of new tissue was formed in the APLGA group, whereas only a
      small amount was formed in the MPLGA group. We verified that the newly formed
      tissue originated from the injected MSCs via GFP testing, and confirmed that the
      created tissue was actual adipose tissue by oil red O staining and Western blot
      (PPAR(gamma) and C/EBP(alpha) were expressed only in APLGA groups). Therefore,
      this study presents an efficient model of adipose tissue engineering using MSCs
      and injectable PLGA spheres.

PMID- 15949552
TI  - Fabrication of viable tissue-engineered constructs with 3D cell-assembly
      technique.
AB  - We have recently developed an organ manufacturing technique that enables us to
      form cell/biomaterial complex three-dimensional (3D) architectures in designed
      patterns. This technique employs a highly accurate 3D micropositioning system
      with a pressue-controlled syringe to deposit cell/biomaterial structures with a
      lateral resolution of 10 microm. The pressure-activated micro-syringe is equipped
      with a fine-bore exit needle using which a wide variety of 3D patterns with
      different arrays of channels (through-holes) were created. The channels can
      supply living cells with nutrients and allow removing the cell metabolites. The
      embedded cells remain viable and perform biological functions as long as the 3D
      structures are retained. The new technology has the potential for eventual high
      throughput production of artificial human tissues and organs.

PMID- 15949553
TI  - Controlling cell adhesion and degradation of chitosan films by N-acetylation.
AB  - As part of our ongoing effort to develop a biodegradable nerve guidance channel
      based on chitin/chitosan, we conducted a systematic in vitro study on the
      biodegradation and neural cell compatibility of chitosan and N-acetylated
      chitosan. The in vitro degradation (pH 7.4, 37 degrees C) in the presence of 1.5
      microg/ml lysozyme showed a progressive mass loss to greater than 50% within 4
      weeks for films with 30-70% acetylation. In contrast, the degradation of samples
      with very low or high acetylation was minimal over the 4-week period. Neural cell
      compatibility of chitosan and N-acetylated chitosan was tested using primary
      chick dorsal root ganglion (DRG) neurons. All chitosan-based films showed DRG
      cell adhesion after 2 days of culture. However, cell viability decreased with
      increasing acetylation. Chitosan that was 0.5% acetylated had the greatest cell
      viability, which was approximately 8 times higher than that of chitosan that was
      11% acetylated. Chitosan with 0.5% and 11% acetylation showed more and longer
      neurites than the other samples studied. Thus chitosan amine content can be tuned
      for optimal biodegradation and cell compatibility, which are important for tissue
      engineering in the nervous system.

PMID- 15949554
TI  - The design and production of Co-Cr alloy implants with controlled surface
      topography by CAD-CAM method and their effects on osseointegration.
AB  - Improved fixation and increased longevity are still important performance
      criteria in the development of orthopaedic prostheses. The osseointegration of a
      series of implant designs made of conventional cobalt-chromium alloy was
      investigated, the shape of each implant being the critical variable. The shape
      was defined by computer-aided design with a view to maximising interdigitation of
      new bone with the implant. Two different process routes, conventional casting and
      selective laser sintering were employed, each process yielded implants that had
      identical surface topology but different microstructures. Hydroxyapatite (HA) was
      used to coat some samples by plasma spraying. Bone formation associated with each
      implant design was delineated through the administration of fluorescent vital
      dyes at three time points following their implantation into New Zealand white
      rabbits. After one month, specimens were harvested, resin embedded, serial
      sectioned and examined under fluorescent light microscopy. The amount of bone
      growth was quantified using image analysis. Plasma spray HA-coated samples
      promoted better osteogenesis and integration than uncoated samples. The extent of
      bone growth associated with identically shaped specimens fabricated by the SLS
      route was markedly greater, attributed to the microstructure of these implants.

PMID- 15949555
TI  - Selective targeting of antibody-conjugated nanoparticles to leukemic cells and
      primary T-lymphocytes.
AB  - In the present study, surface-modified nanoparticles based on biodegradable
      material were used for antibody coupling in order to get a selective drug carrier
      systems. Gelatin nanoparticles were prepared by a desolvation process. Sulfhydryl
      groups were introduced which enabled the linkage of NeutrAvidin (NAv). Antibodies
      specific for the CD3 antigen on lymphocytic cells were conjugated to the
      nanoparticles surface. The binding of biotinylated anti-CD3 antibody was achieved
      by NAv-biotin-complex formation. Cellular binding and uptake were determined by
      flow cytometry and confocal laser scanning microscopy (CLSM). Cell-type-specific
      targeting of anti-CD3-conjugated nanoparticles into CD3-positive human T-cell
      leukemia cells and primary T-lymphocytes could be shown. Celluar uptake and
      effective internalization of antibody-conjugated nanoparticles into CD3
      expressing cells were demonstrated. Uptake rates of about 84% into T-cell
      leukemia cells were observed. To confirm selectivity of T-cell targeting,
      competition experiments were carried out adding excessive free anti-CD3 prior to
      nanoparticle incubation leading to significantly reduced cellular uptake of
      antibody-conjugated nanoparticles. Further analysis on the mechanism of uptake
      confirmed a receptor-mediated endocytotic process. Protein-based nanoparticles
      conjugated with an antibody against a specific cellular antigen hold promise as
      selective drug delivery systems for specific cell types.

PMID- 15949556
TI  - Interaction of various pectin formulations with porcine colonic tissues.
AB  - Pectins of low and high degrees of esterification, as well as pectin derivatives
      carrying primary amines, were investigate for gel forming ability with mucosal
      tissues. The combination of scanning electronic microscopy and small deformation
      dynamic mechanical studies revealed that pectins with higher net electrical
      charges are more bioadhesive than the less charged ones. Both the negatively
      charged pectin formulation, P-25, and the positively charged formulation, P-N,
      were able to synergize with the mucus to produce rheologically strengthened gels.
      The highly esterified pectin, P-94, also synergized with the mucosal
      glycoproteins to form a gel structure via coil entanglements. The ex vivo studies
      further confirmed the microstructures of mucus gel networks with adsorbed
      pectins. When incubated with porcine intestinal mucus membrane, P-94 gels were
      found generally bound to the lumen area, P-25 gels were able to penetrate deeply
      near the wall area, P-N gels interacted with mucins via electrostatic bonding and
      dispersed into the whole area from the lumen to the wall. Hence, both P-N and P
      94, by enhancing the protective barrier properties of mucus systems, may be
      useful alternatives for the treatment of mucus related irritation and infection.
      In drug-delivery systems, P-N and P-25 would deliver incorporated drugs mainly by
      pectin dissolution, while a diffusion mechanism would release drugs from P-94
      gels.

PMID- 15949557
TI  - An inverted microcontact printing method on topographically structured
      polystyrene chips for arrayed micro-3-D culturing of single cells.
AB  - With the goal to investigate the relation of shape and function of single cells
      or clusters of cells in a 3-dimensional (3-D) microenvironment, we present a
      novel platform technology to create arrays of microwells on polystyrene (PS)
      chips for hosting cells in a local microenvironment characterized by controlled
      shape and surface chemistry. The micro-3-D cell culturing combines 2-dimensional
      chemical patterning with topographical microstructuring presenting to the cells a
      local 3-D host structure. Microwells of controlled dimensions were produced by a
      two-step replication process, based on standard microfabrication of Si, replica
      molding into poly(dimethylsiloxane), and hot embossing of PS. This allowed the
      production of large numbers of microstructured surfaces with high reproducibility
      and fidelity of replication. Using inverted micro contact printing, the plateau
      surface between the microwells was successfully passivated to block adsorption of
      proteins and prevent cell attachment by transfer of a graft-copolymer, poly(l
      lysine)-g-poly(ethylene glycol). The surface inside the microwells was
      subsequently modified by spontaneous adsorption of proteins or functionalized PLL
      g-PEG/PEG-X (X=biotin or specific, cell-interactive peptide) to elicit specific
      responses inside the wells. Preliminary cell experiments demonstrated the
      functionality of such a device to host single epithelial cells (MDCK II) inside
      the functionalized microwells and thus to control their 3-D shape. This novel
      platform is useful for fundamental cell-biological studies and applications in
      the area of cell-based sensing.

PMID- 15949558
TI  - Natural history of fetal cell microchimerism during and following murine
      pregnancy.
AB  - In humans, fetal cells enter the maternal circulation during all pregnancies and
      can persist for decades. Human studies, however, are often limited by the number
      of subjects and the availability of healthy and diseased tissues for analysis. We
      sought to develop a murine model to establish the natural history of fetal cell
      microchimerism in various maternal tissues during and after healthy pregnancies
      resulting from congenic and allogenic matings. We bred C57BL/6J and DBA/2J virgin
      female mice to C57BL/6J males transgenic for the enhanced green fluorescent
      protein (GFP), which shows autosomal dominant inheritance with complete
      penetrance and is under the control of a ubiquitous chicken beta-actin promoter
      and a cytomegalovirus enhancer. During pregnancy and at different times after
      delivery, female mice were sacrificed. Tissues were collected and the presence of
      the gfp transgene and GFP+ cells was assessed by real-time quantitative PCR and
      by immunofluorescence. During pregnancy, microchimerism was detected in all
      tissues from mice carrying GFP+ fetuses. Fetal cells were often mononuclear. The
      frequency of fetal cells in the lungs was significantly higher compared to other
      tissues. The level of microchimerism was also significantly higher in congenic
      compared to allogenic matings. After delivery, the frequency of fetal cells
      decreased and fetal cells were undetectable at 2 and 3 weeks after the first
      delivery. However, some mice that had three gestations had detectable fetal cells
      3 weeks after their last delivery. Using sensitive methods of detection, we
      demonstrate that fetal cell microchimerism occurs during all murine pregnancies.
      We describe a useful model for the study of the consequences of this phenomenon.

PMID- 15949559
TI  - Fas ligand in the uterus of the non-pregnant mouse induces apoptosis of CD4+ T
      cells.
AB  - The role of FasL in the reproductive tissues of the non-pregnant mouse may be the
      induction of apoptosis of activated T cells for the prevention of unwanted
      inflammatory responses secondary to infection. This study was undertaken to
      identify cell and tissue types that typically express FasL in the uterus and
      oviduct of the mouse and to establish whether FasL on the surface of these cells
      was able to induce T cell apoptosis. FasL in the mouse uterus and oviduct was
      demonstrated using three independent methods: RT-PCR, Western blot and
      immunocytochemistry. The protein was present in the epithelial and mesenchymal
      cells of the uterus and showed a granular pattern in the apical epithelial
      portion. Although this suggests the presence of vesicles, surface expression was
      also detected by flow cytometry of isolated uterine cells. Exogenous
      administration of estradiol and progesterone had no significant effect on the
      expression and localization of FasL. The ability of uterine cells to induce FasL
      dependent apoptosis of activated CD4+T cells was examined by incubation of
      phytohemagglutinin-treated T cells with cultured uterine cells. TUNEL and flow
      cytometric analyses showed that CD4+T cells experienced apoptosis after 5h of co
      incubation. Neutralizing antibodies inhibited apoptosis demonstrating that a
      biologically active FasL is present in the reproductive tissues of the mouse.
      Results indicate that FasL is a biologically active molecule present in
      epithelial and mesenchymal cells of the uterus and the oviduct of the non
      pregnant mouse that might restrain local immune response by induction of
      apoptosis of CD4+T lymphocytes.

PMID- 15949560
TI  - Lipopolysaccharide-binding protein is produced in the epididymis and associated
      with spermatozoa and prostasomes.
AB  - Lipopolysaccharide-binding protein (LBP) is an acute phase protein known to play
      a central role in the defense against Gram-negative bacteria. It binds
      lipopolysaccharides of Gram-negative bacteria and, after binding to CD14, the
      complex signals through Toll-like receptor (TLR)-4, eliciting host-defense
      responses, such as cytokine production, in inflammatory cells. The present study
      demonstrates constitutive expression of the gene encoding lipopolysaccharide
      binding protein in the epithelium of the human epididymis by in situ
      hybridization. Using immunohistochemistry lipopolysaccharide-binding protein was
      shown to be present in the same cells and also attached to the heads and tails of
      spermatozoa. Cell-free seminal plasma, lysed spermatozoa and lysed prostasomes
      were subjected to Western blot; all showed immunoreactive bands corresponding to
      the size of lipopolysaccharide-binding protein. Gel filtration demonstrated that
      lipopolysaccharide-binding protein colocalizes with prostasomes. The
      concentration of lipopolysacharide-binding protein in seminal plasma was 127+/
      42ng/mL (mean+/-S.D.; range 73-215ng/mL). Taken together, our results suggest
      roles for lipopolysaccharide-binding protein during human reproduction.

PMID- 15949561
TI  - Heparin treatment in pregnancy loss: Potential therapeutic benefits beyond
      anticoagulation.
AB  - Interventions with heparin therapies have increased fetal survival in patients
      with antiphospholipid syndrome (APS). In this review, several physiological and
      pharmacological effects of heparin are described. These different mechanisms of
      action could explain the beneficial effects of heparin in the treatment of
      recurrent pregnancy loss in patients with APS. In addition to direct effects of
      heparin on the coagulation cascade, heparin might protect pregnancies by reducing
      the binding of antiphospholipid antibodies, reducing inflammation, facilitating
      implantation and or inhibiting complement activation.

PMID- 15949562
TI  - Circulating auto-antibodies against the zona pellucida and thyroid microsomal
      antigen in women with premature ovarian failure.
AB  - Premature ovarian failure (POF) is a disorder of multicausal etiology leading to
      infertility in women. Development of ovarian auto-antibodies is a causative
      factor in most POF cases, but no consensus on the ovarian antigenic determinants
      has been reached till date. In the present study, sera from 15 POF cases, seven
      normally cycling women and eight menopausal women were studied by
      immunohistochemistry (IHC) for the presence of anti-ovarian antibodies. 10 of the
      15 POF sera (66.6%) presented with anti-ovarian antibodies (Ao). Of these, two
      demonstrated antibodies to the zona pellucida (ZP) as well as strong
      immunoreactivity to granulosa cells (Azg), while the remaining eight exhibited
      anti-ZP antibodies with negligible staining in granulosa cells (Az). The
      antibodies showed cross-reactivity with ZP from various species such as human,
      sheep, marmoset, pig and mouse. Among various murine tissues, the antibodies
      cross-reacted only with thyroid and not with uterus, spleen, kidney, liver,
      adrenal, pancreas and pituitary. Five of the eight Az individuals presented with
      significant titres of anti-thyroid antibodies (Azt). In the control group, one
      menopausal control presented with reactivity to both ZP and GC, the autoimmunity
      possibly being a consequence of surgical trauma; while one normally cycling woman
      tested positive for anti-thyroid antibodies. The IHC results were confirmed by
      ELISA using heat-solubilized isolated ZP (SIZP) as the antigen. Out of seven Ao
      samples assessed by ELISA, five reacted with SIZP. Preincubation of these five
      samples with varying concentrations of SIZP demonstrated a dose-dependent
      decrease in reactivity in ELISA and abolished staining in IHC, confirming the
      specificity of auto-antibodies to ZP in the POF group. Our results thus suggest
      that ZP is an important ovarian antigen in autoimmune POF.

PMID- 15949563
TI  - Indications of an altered immune balance in preeclampsia: a decrease in in vitro
      secretion of IL-5 and IL-10 from blood mononuclear cells and in blood basophil
      counts compared with normal pregnancy.
AB  - It has been suggested that maladaptation of the maternal immune response during
      pregnancy might be a causal factor for preeclampsia. This study was designed to
      examine the systemic immune status at both the innate level and the adaptive
      level in pregnancies complicated by preeclampsia (n=15) and normal pregnancies
      (n=15). Spontaneous and in vitro-induced secretion of IL-5, IL-6, IL-10, IL-12,
      IL-13 and TNF-alpha, in response to paternal blood cells and the vaccination
      antigens purified protein derivate of tuberculin (PPD) and tetanus toxoid (TT),
      was detected in cell culture supernatants from blood mononuclear cells by ELISA.
      Preeclamptic women showed reduced numbers of basophil granulocytes in the blood
      (p=0.004) and lower spontaneous secretion of IL-5 from blood mononuclear cells
      (p=0.016). In addition, paternal antigen-induced secretion of IL-10 was decreased
      in preeclampsia compared with normal pregnancy (p=0.012). No further differences
      between preeclampsia and normal pregnancy were found for any stimuli or
      cytokines. The present findings of reduced basophil numbers and lower spontaneous
      in vitro secretion of IL-5 in preeclampsia compared with normal pregnancy
      indicate a decrease in systemic Th2 immunity in preeclampsia. Furthermore, the
      decrease in paternal antigen-induced secretion of the immunosuppressive cytokine
      IL-10 in preeclampsia indicates a fetus-specific decrease in immunosuppression
      mediated by blood mononuclear cells. Whether these systemic changes are a cause
      or a consequence of preeclampsia remains to be elucidated.

PMID- 15949564
TI  - Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines.
AB  - Deletions of chromosome 1p and 19q arms are frequent genetic abnormalities in
      primary human gliomas and are especially common in oligodendrogliomas. However,
      the chromosome 1p and 19q status of many glioma cell lines has not been
      established. Using homozygosity mapping, fluorescence in situ hybridization
      (FISH), and comparative genomic hybridization to arrayed BAC (CGHa), we screened
      17 glioma cell lines for chromosome 1 and 19 deletions. Sequence tagged site
      polymorphisms were used to evaluate the cell lines for regions of chromosome 1p
      and 19q homozygosity. Cell lines A172, U251, TP265, U118, SW1088, U87, SW1783,
      and D32 contained significant regions of 19q homozygosity. In addition, A172,
      U87, TP483, D37, U118, MO67, and TP265 contained significant regions of 1p
      homozygosity. FISH probes localized to 1p36.32 and 19q13.33 as well as CGHa were
      used to determine which cell lines had deletions of 1p and/or 19q. Cell lines
      A172, U87, TP483, TP265, H4, U251, and D37 were deleted for portions of 1p. CGHa
      and homozygosity mapping of these cell lines define a 700-kilobase (Kb) common
      deletion region that is encompassed by a larger deletion region previously mapped
      in sporadic gliomas. This common deletion region is localized at 1p36.31 and
      includes CHD5, a putative tumor suppressor gene. Cell line A172 was observed to
      have a deletion between 19q13.33 and 19q13.41, while U87 was observed to have a
      smaller deletion of 19q13.33. Cell lines A172 and U87 contain 1p and 19q
      deletions similar to those found in sporadic gliomas and will be useful cellular
      reagents for evaluating the function of putative 1p and 19q glioma tumor
      suppressor genes.

PMID- 15949565
TI  - Chromosome 7 abnormalities are common in chordomas.
AB  - Chordomas are malignant bone tumors most often located in the axial skeleton. The
      estimated 5-year patient survival rate is between 50 and 80%. The cytogenetic and
      molecular genetic features of chordomas are largely unknown but, from what can be
      seen, appear to be complex. Near-diploid karyotypes have been detected by G
      banding analysis, and comparative genomic hybridization (CGH) has revealed losses
      of or from chromosome arms 1p and 3p, as well as partial or whole copy number
      gains of chromosomes 7 and 20. We provide additional molecular cytogenetic
      information about six sacral chordomas examined by CGH and interphase
      fluorescence in situ hybridization (IP-FISH). By CGH, gains of chromosomal areas
      1q23 approximately q24 (three tumors), 7p21 approximately p22 (three tumors), 7q
      (four tumors), and 19p13 (three tumors), as well as loss of chromosomal segment
      9p22 approximately p23 (three tumors), were the most frequently observed
      imbalances. These results are concordant with earlier CGH data, although loss of
      or from chromosome arms 1p and 3p was not found as frequently in this series;
      both were detected in only one tumor. IP-FISH confirmed the CGH findings and
      showed that chromosome 7 was polysomic in four of the tumors. All these samples
      had trisomic and tetrasomic clones for chromosome 7, and two of them had
      pentasomic clones as well.

PMID- 15949566
TI  - Coexistence of different clonal populations harboring the b3a2 (p210) and e1a2
      (p190) BCR-ABL1 fusion transcripts in chronic myelogenous leukemia resistant to
      imatinib.
AB  - In this study, we report the case of a Philadelphia (Ph) positive chronic
      myelogenous leukemia (CML) patient with the presence of p190 and p210 BCR-ABL1
      mRNA fusion transcripts derived from e1a2 and b3a2 BCR-ABL1 genomic
      rearrangements, respectively. The presence of e1a2 BCR-ABL1 genomic rearrangement
      was seen in 2 different clones, one with the rearrangement and another one with
      the rearrangement and deletion of the BCR gene of the non-rearranged chromosome
      22. After treatment with imatinib, the p210 transcript could not be detected,
      whereas p190 was still present 6 months after initiation of imatinib therapy and
      progression to blast phase. The absence of p210 transcript post treatment
      indicates that the clone with b3a2 responded to imatinib and that the observed
      resistance was associated to cells harboring the e1a2 genomic rearrangement.
      Despite resistance of this patient to imatinib, no evidence of mutations in the
      kinase domain of ABL1 was found. Loss of normal BCR in one cell clone may
      contribute to the resistance to imatinib due to the lack of BCR mediated
      inhibition of BCR-ABL1.

PMID- 15949567
TI  - Incidence of chromosomal anomalies detected with FISH and their clinical
      correlations in B-chronic lymphocytic leukemia.
AB  - B-chronic lymphocytic leukemia (B-CLL) is the most common adult leukemia.
      Molecular genetic characterization of B-CLL has made significant progress and
      typical chromosomal anomalies have been assessed. The most frequent chromosomal
      abnormalities are deletions at 13q14, 17p13, and 11q22 approximately q23 and
      trisomy 12. The aim of this study was to establish incidence of chromosomal
      changes in bone marrow or peripheral blood cells (or both) of B-CLL patients
      using a molecular cytogenetic method, interphase fluorescence in situ
      hybridization (I-FISH), and to evaluate the prognostic implications. We performed
      I-FISH on bone marrow and blood smears from 217 B-CLL patients (124 male, 93
      female). Trisomy 12 was found in 35 of the 217 (16%); deletion 13q14 was analyzed
      in 207 patients and found in 112 (54%). Deletion 17p13 was found in 34 (16%) out
      of 206 examined. Deletion of 11q23 was analyzed in 56 patients and was present in
      7 (12%). Statistical analyses were performed to correlate the molecular
      cytogenetic findings with disease status (stable versus progressive), Rai stage,
      CD38/CD19 antigen coexpression, immunoglobulin variable heavy chain (IgV(H))
      mutational pattern, and other clinical and laboratory parameters. No apparent
      differences in distribution were noted for anomalies +12, del(13)(q14), or
      del(17)(p13) among patients with stable and progressive disease, and no
      consistent pattern in the distribution of type of genomic changes were found
      among various Rai stages and in CD38/CD19-positive or -negative patients.
      Patients without IgV(H) mutation had a worse prognosis; however, distribution of
      chromosomal abnormalities identified with FISH was the same for patients with and
      without IgV(H) mutations.

PMID- 15949568
TI  - In silico chromosomal clustering of genes displaying altered expression patterns
      in ovarian cancer.
AB  - Ovarian cancer, the leading cause of death due to gynecological malignancy, is
      diagnosed in most cases at an advanced stage. Combined with the paucity of
      symptoms of early-stage disease, the need to develop novel effective markers for
      the detection of potentially curable, early-stage disease is self-evident.
      Comprehensive analyses of somatic gene expression patterns in ovarian cancer were
      reported previously (n=17) and yielded substantial information on somatically
      altered genes, information that can potentially be useful in developing early
      detection markers. To further substantiate the role that these genes play in
      ovarian cancer tumorogenesis, we surveyed these reports and arranged the
      significantly altered genes from all reported studies by their chromosomal
      location (in silico chromosomal clustering). Subsequent comparison of this
      clustering to known genomic somatic alterations at the DNA level from data
      obtained using comparative genomic hybridization (CGH) was carried out. The major
      chromosomal regions that displayed overexpressed genes were correlated with the
      major CGH-detectable DNA amplification areas at 20q (harboring HE4, SLPI, MYBL2,
      UBE2C, and SDC4) and 1q (harboring MUC1). These genes may provide insights into
      ovarian cancer pathogenesis and may also prove to be useful as early detection
      tools.

PMID- 15949569
TI  - Allelic loss of 3p25 associated with alterations of 5q22.3 approximately q23.2
      may affect the prognosis of conventional renal cell carcinoma.
AB  - Little is known about the clinical significance at the frequent association of 3p
      loss with 5q gain/loss in conventional renal cell carcinoma (RCC). We analyzed
      the clinical significance of copy number gain and loss at 5q21 approximately q23
      combined with allelic loss of 3p25 (including the VHL gene). Fifty RCCs were
      examined by dual-color fluorescence in situ hybridization with DNA probes for
      D3Z1 (3cen), cCI3-865 (3p25.1 approximately p25.3), D5S23 (5p15.2), cCI5-243
      (5q21.2 approximately q21.3), and cCI5-215 (5q22.3 approximately q23.2). In
      patients who had 3p loss, there was a significant association of loss at 5q22.3
      approximately q23.2 with large tumors (>7 cm) and high-grade tumors (both P <
      0.05), whereas gain at 5q22.3 approximately q23.2 was associated with low-grade
      tumors (P < 0.05). There was also a significant association loss at 5q21.2
      approximately q21.3 high-grade tumors in patients with 3p loss (P < 0.05).
      Patients with 3p loss and gain at 5q22.3 approximately q23.2 had a significantly
      better disease-specific survival than those who had 3p loss without such gain (P
      < 0.05). Allelic loss of 3p25 including the VHL gene is thought to be an
      immediate event in the development of conventional RCC. Copy number gains or
      losses of 5q21 approximately q23 are thought to be events that lead to tumor
      progression although the clinical significance of either gains or losses is not
      well known.

PMID- 15949570
TI  - Increased risk of cervical cancer associated with cyclin D1 gene A870G
      polymorphism.
AB  - Human papillomavirus (HPV) plays a major role in the etiology of cervical cancer.
      However, a complex correlation between viral and cellular genes is necessary for
      cell cycle control deregulation in the progression to invasive cervical cancer
      (ICC). Cyclin D1 (CCND1) is an important positive regulator of the G1/S phase of
      the cell cycle. The CCND1 gene is located at 11q13 and is often altered in human
      cancers. We analyzed the A870G CCND1 polymorphism by polymerase chain
      reaction/restriction fragment length polymorphism analysis in 246 women including
      50 cases with high-grade squamous intraepithelial lesions of the cervix (HSIL),
      93 with ICC, and 103 healthy women. The GG genotype was associated with a 4.32
      fold higher risk for the development of HSIL [adjusted odds ratio (aOR)=4.32, 95%
      confidence interval (CI) 1.50-12.46, P=0.0067), and a 3.26-fold increased risk
      for the development of ICC (aOR=3.26, 95% CI 1.42-7.53, P=0.006). The proportion
      of cervical cancer cases attributable to the GG CCND1 genotype was 17.26%. This
      study indicates that the A870G CCND1 polymorphism could act as a cofactor of HPV
      in the initiation of cervical carcinogenesis, particularly in the transformation
      zone of HPV-infected women, supporting evidence for a genetic factor in ICC risk.

PMID- 15949571
TI  - Genetic polymorphism in the sulfotransferase SULT1A1 gene in cancer.
AB  - Cytosolic sulfotransferases are enzymes that catalyze the conjugation of sulfate
      groups to a variety of xenobiotic and endogenous substrates. A mutation in the
      SULT1A1 gene has been associated with decreased sulfotransferase activity. We
      studied 125 cancer patients and 100 healthy controls from Brazil matched by age
      and gender. The objective of this study was to assess the impact of the SULT1A1
      polymorphism on sulfotransferase activity in a population of cancer patients.
      Both heterozygous and homozygous individuals for the mutant allele had
      significantly decreased sulfotransferase enzymatic activity. This decrease was
      more significant in cancer patients. The frequency of the SULT1A1( *)2 allele was
      increased in the myeloma group (odds ratio=0.53). These data suggest a functional
      role for the SULT1A1 gene polymorphism in cancer.

PMID- 15949572
TI  - Large genomic aberrations in MSH2 and MLH1 genes are frequent in Chinese
      colorectal cancer.
AB  - Hereditary nonpolyposis colorectal cancer is caused by inactivating mutations in
      the genes of the DNA mismatch repair (MMR) system. Studies have shown that large
      fragment aberrations in MMR genes are responsible for a considerable proportion
      of hereditary colorectal cancer (CRC), but it has been rarely reported in Chinese
      patients. Here we used multiplex ligation-dependent probe amplification to
      analyze the genomic rearrangements of 45 Chinese hereditary CRC families, 20
      young-age CRC patients (onset of CRC at younger than 50 years and no family
      history), and 13 patients with sporadic CRC diagnosed at age 50 years or older.
      Overall, we found 9 (13.8%) large genomic deletions or duplications: 7 out of 45
      CRC patients with family history and 2 out of 20 young CRC patients. In all
      alterations, five genomic deletions were uncovered in the MSH2 gene, as well as
      one deletion and three duplications in the MLH1 gene. Furthermore, two of the
      duplications unveiled in this study may have more than a four-copy increase of
      the exon showing duplication in MLH1. The results indicate that genomic
      aberrations, large-fragment deletions and duplications, in both MSH2 and MLH1
      genes play a role in the pathogenesis of Chinese CRC patients with a family
      history, as reported in western populations. Moreover, the genomic aberrations in
      these genes might also be a frequent cause of CRC at a young age in China.

PMID- 15949573
TI  - Hematological, immunophenotypic, and cytogenetic characteristics of acute
      myeloblastic leukemia with trisomy 11.
AB  - We evaluated the incidence of trisomy 11 in acute myeloblastic leukemia (AML) and
      its correlation with the most relevant clinical, biological, and immunophenotypic
      disease characteristics in a total of 399 consecutive AML patients. Trisomy 11
      was found in 15 patients (3.8%), in 3 of them as the sole abnormality. Median age
      was 68 years (range 48-87); 87% of patients were older than 60 years. Seven
      patients displayed multilineage dysplasia. Cytogenetics showed an association
      with trisomy 8 in six patients, and in five cases with a del(5q); nine patients
      had complex karyotypes. In all cases, in situ hybridization studies revealed
      three copies of the MLL gene, but no rearrangements or tandem duplications of
      MLL. Immunophenotypic analysis of blast cells showed a constant immature
      immunophenotypic profile with CD34 or CD117 expression (or both) in all cases
      analyzed. The complete remission rate was 43%; median survival time was only 2
      months.

PMID- 15949574
TI  - Chronic myelogenous leukemia occurring in two brothers diagnosed 26 years apart.
AB  - Chronic myelogenous leukemia (CML) is characterized by the presence of the
      chromosomal abnormality t(9;22)(q34;q11), which is detected in more than 90% of
      cases. Despite great strides in our understanding of this disease, few
      predisposing etiologic factors have been identified. We report on the case of a
      45-year-old man with Philadelphia chromosome-positive, BCR-ABL fusion-positive
      chronic-phase CML, whose brother had succumbed to the same disease 22 years
      earlier. While a coincidental familial occurrence cannot be excluded in this
      case, we believe that this report underscores the need for further investigation
      of possible unknown environmental or heritable etiologic factors in this disease.

PMID- 15949575
TI  - Acquired inv(9): what is its significance?
AB  - Pericentric inversion of the heterochromatic region of chromosome 9 [inv(9)] is a
      common heteromorphism in the general population. It is presumed familial as there
      are no reports of de novo inv(9) chromosomes in constitutional karyotypes. We
      report 2 cases of acquired inv(9) chromosomes; 1 patient with acute myeloid
      leukemia, 46,XY,inv(9)(p11q13)[11]/46,XY[9], and a second with severe anemia,
      46,XX,inv(9)(p11q13)[14]/46,XX[6]. The acquired nature of the inv(9) was
      confirmed by constitutional karyotyping and/or molecular analysis. The inv(9) in
      these patients may be a de novo inversion that cytogenetically mimics the
      constitutional inv(9) heteromorphism. Alternatively, it may be the result of
      neocentromere activation in 9q due to epigenetic events associated with the
      disease in these patients that results in a metacentric chromosome similarly
      mimicking the constitutional inv(9). One previous report of an acquired inv(9)
      was in a patient with essential thrombocythemia. The differences in clinical
      presentation may represent different underlying mechanisms generating the inv(9).
      The significance of an acquired inv(9) is unknown and will require reporting of
      additional cases.

PMID- 15949576
TI  - Telomere stability genes are not mutated in osteosarcoma cell lines.
AB  - Osteosarcoma (OS), the most common primary bone tumor in adolescents and young
      adults, is characterized by a high degree of chromosomal abnormalities. Because
      telomeres are important for maintaining chromosomal integrity, it is plausible
      that germ-line or somatic mutations in the genes responsible for stabilizing the
      telomere complex could contribute to OS. We performed bi-directional sequence
      analysis in five OS cell lines and targeted all exons and proximal promoter
      regions in eight genes important in telomere stability: telomerase, the RNA
      component of telomerase (TERC), telomeric repeat binding factor 1, telomeric
      repeat binding factor 2, TERF1 interacting nuclear factor 2, human Rap1,
      protection of telomeres 1 and tankyrase. In this pilot study, we did not identify
      either somatic mutations or novel germ-line mutations in the five cell lines
      studied. However, we did confirm common genetic polymorphisms; an analysis of
      heterozygous sites suggests that loss of heterozygosity in OS is not present
      across these eight genes.

PMID- 15949577
TI  - Aberrations of 11q13 in laryngeal squamous cell lines and their prognostic
      significance.
AB  - Chromosomal aberrations were analyzed in 12 established cell lines derived from
      laryngeal squamous cell carcinoma. Cytogenetic and fluorescence in situ
      hybridization studies were used to identify aberrations in the 11q13 region and
      in some other chromosome regions. Amplification of 11q13 was established only in
      the cell lines derived from subjects with a survival period of less than 5 years
      and, together with the 3q gain, were the only chromosomal structural
      abnormalities connected with short survival. In this group we also found
      translocations with a breakpoint within 11q13. In three cell lines, 11q13 was
      observed as a homogenously staining region. The results suggest that
      amplification of 11q13, as well as re-arrangements potentially involved in up
      regulation of the oncogenes mapped in 11q13, should be considered as markers of
      poor prognosis in laryngeal cancer. A diagnostic significance of 11q13 may be
      increased by a parallel determination with 3q gain.

PMID- 15949578
TI  - A der(14)t(1;14)(q12;p11) in chronic myelomonocytic leukemia.
AB  - Duplication of the long arm of chromosome 1 (1q) is widely reported in human
      neoplasia, including the myelodysplastic syndromes (MDS). So far, it has not been
      described as a single aberration in the chronic myelomonocytic leukemia (CMML), a
      subtype of MDS. Rather, trisomy 1q was always a part of complex chromosome
      changes affecting the subtypes of MDS other than CMML. We report on a patient
      with CMML with an unbalanced translocation of the entire 1q onto the short arm of
      chromosome 14 as a sole cytogenetic abnormality. Fluorescence in situ
      hybridization (FISH) analysis with an alpha-satellite probe for the paracentric
      region of the long arm of chromosome 1 confirmed the presence of trisomy 1q in a
      derivative chromosome, der(14)t(1;14)(q12;p11). The discrepant results between
      the metaphase cytogenetics (100% abnormal) and interphase cytogenetic (71% nuclei
      with 3 signals) suggest that trisomy 1q, even in the absence of additional
      cytogenetic changes, has a sufficient leukemogenic potential to confer a
      proliferative advantage on hematopoietic cells committed to monocyte stemline
      both in vitro and in vivo. The literature data on partial and complete trisomy 1q
      in CMML is reviewed.

PMID- 15949579
TI  - Cryptic chromosomal anomaly in a patient with acute myeloid leukemia leading to
      AML1/ETO fusion with unfavorable prognostic factors.

PMID- 15949581
TI  - Analyzing a complex visuomotor tracking task with brain-electrical event related
      potentials.
AB  - Non-invasive techniques such as neuroimaging and event-related potential (ERP)
      methods have dramatically enhanced our understanding of the human brain.
      According to the requirements of the applied method, it is useful to simplify
      tasks for methodological reasons. In the present study we tested whether ERP
      measures are also suitable for analyzing complex tasks. In order to do this, we
      developed an analysis strategy based on the post hoc analysis of the behavioural
      data. We applied this method to a pursuit-tracking task of 25 s trial duration,
      consisting of repeated and non-repeated waveforms, where subjects had to track a
      target cross with a mouse-controlled cursor cross. An EEG was recorded from 62
      channels. Response-locked ERPs were computed for two types of error correction:
      the correction of errors induced externally by the change of target direction and
      of internal errors generated by the subject itself. We found several ERP
      components that could be assigned to different feedback and feedforward
      controlled processing steps in the frontoparietal circuitry underlying visuomotor
      control, such as movement planning, movement execution (motor potential),
      reafferent activity, visuospatial analysis, and attentional (P300) processes. Our
      results support newer models that propose a role for the posterior parietal
      cortex in integrating multimodal sensory information. In addition, fast (about
      180 ms and probably facilitated by anticipation) and slow (about 230-260 ms)
      error corrections could be differentiated by the time course of ERP activity. Our
      results show that complex (motor) tasks can be investigated with ERPs. This opens
      fruitful perspectives for future research on motor control in an ecological
      setting.

PMID- 15949582
TI  - Interaction of neuromuscular, spatial and visual constraints on hand-foot
      coordination dynamics.
AB  - In the present study, we investigated the contributions of motor and perceptual
      processes to directional constraints as observed during hand-foot coordination.
      Participants performed cyclical flexion-extension movements of the right hand and
      foot under two coordination modes: in-phase (isodirectional) and antiphase (non
      isodirectional). Those tasks were performed either with full vision or no vision
      of the limbs. Depending on the position of the forearm (prone or supine), the
      coordination patterns were performed with similar and dissimilar neuro-muscular
      coupling with respect to their phylogenetic origin as antigravity muscles.
      Results showed that the antiphase pattern was more difficult to maintain than the
      in-phase pattern and that neuro-muscular coupling significantly influenced the
      coordination dynamics. Moreover, the effect of vision differed as a function of
      both neuro-muscular coupling and coordination mode. Under dissimilar neuro
      muscular coupling, the presence of visual feedback stabilized the in-phase
      pattern and destabilized the antiphase pattern. In contrast, visual feedback did
      not influence pattern stability during conditions of similar neuro-muscular
      coupling. These results shed light on the complex interactions between motor and
      perceptual (visual) constraints during the production of hand-foot coordination
      patterns.

PMID- 15949583
TI  - Optimum take-off angle in the standing long jump.
AB  - The aim of this study was to identify and explain the optimum projection angle
      that maximises the distance achieved in a standing long jump. Five physically
      active males performed maximum-effort jumps over a wide range of take-off angles,
      and the jumps were recorded and analysed using a 2-D video analysis procedure.
      The total jump distance achieved was considered as the sum of three component
      distances (take-off, flight, and landing), and the dependence of each component
      distance on the take-off angle was systematically investigated. The flight
      distance was strongly affected by a decrease in the jumper's take-off speed with
      increasing take-off angle, and the take-off distance and landing distance
      steadily decreased with increasing take-off angle due to changes in the jumper's
      body configuration. The optimum take-off angle for the jumper was the angle at
      which the three component distances combined to produce the greatest jump
      distance. Although the calculated optimum take-off angles (19-27 degrees) were
      lower than the jumpers' preferred take-off angles (31-39 degrees), the loss in
      jump distance through using a sub-optimum take-off angle was relatively small.

PMID- 15949584
TI  - Teachers' ratings of gross motor skills suffer from low concurrent validity.
AB  - In this study an attempt was made to construct a reliable and valid unifactorial
      teachers' rating scale for gross motor ability. Study 1 (132 children from 3 to 7
      years) revealed that reliability of the scale was acceptable and that the scale
      represented an unifactorial dimension. Two studies on concurrent validity of the
      scale with an experimental gross motor task (stepping-stone crossing), the
      unifactorial subtest Locomotion of the Test of Gross Motor Development and the
      subtest Balance of the Movement Assessment Battery for Children as criterion
      measures, did not produce acceptable validity coefficients. In both validation
      studies an age effect was found. It was concluded that factor specificity does
      not seem the answer to the usual low validity coefficients of multifactorial
      teachers' rating scales. An alternative approach is suggested in which the
      assessment of functional activities in daily situations is stressed. Finally, the
      inclusion of atypical groups in random samples, which is common practice in
      research on concurrent validity of screening instruments for children's motor
      problems, is discussed.

PMID- 15949585
TI  - Circulating tumour-derived DNA and RNA markers in blood: a tool for early
      detection, diagnostics, and follow-up?
AB  - BACKGROUND: Lung cancer is the most common cause of cancer death in developed
      countries. The prognosis is poor with only 10-15% of patients surviving 5 years
      after diagnosis. This dismal prognosis is attributed to the lack of efficient
      diagnostic methods for early detection and lack of successful treatment for
      metastatic disease. Within the last decade, rapid advances in molecular biology
      and radiology have provided a rational basis for improving early detection and
      patients' outcome. A non-invasive blood test effective in detecting preneoplastic
      changes or early lung cancer in high risk individuals has been perceived as a
      holy grail by cancer researchers. METHODS: The introduction of polymerase chain
      reaction (PCR)-based technology in the late 1980s and its refinement over the
      last 10 years have allowed us to detect and quantify extremely small amounts of
      tumour-derived nucleic acids. This has led to an increased knowledge of the
      molecular pathogenesis of lung cancer and a basis for the use of DNA and RNA
      markers in blood for early cancer detection, diagnostics, and follow-up. Common
      genetic alterations in lung carcinogenesis are already well known. We reviewed
      published literature on DNA and RNA in plasma or serum in lung cancer patients up
      to 2004, with particular emphasis on reports published since 1995. RESULTS:
      Twenty-two clinical studies have evaluating the role of DNA and RNA aberrations
      in the blood of lung cancer patients. A total of 1618 (range 10-163/study) cases
      and 595 (range 10-120/study) control cases were evaluated, and overall
      plasma/serum abnormalities were found in 43% (range 0-78%) of cases and 0.8% of
      healthy controls. For (1) total DNA and gene expression levels, 61% (range 53
      71%) of cases and 0.9% of controls; (2) oncogene mutations, 16% (range 0-30%) and
      0%; (3) microsatellite alterations, 46% (range 24-71%) and 21% (controls with non
      malignant pulmonary disease); (4) promoter methylation, 42% (range 5-73%) and 0%;
      (5) tumour-related RNAs, 54% (range 39-78%) and 6%. In general, the studies
      contain small series of lung cancer patients and even smaller or missing case
      control groups. CONCLUSION: The analysis of circulating DNA or RNA in plasma is a
      promising non-invasive diagnostic tool, requiring only a limited blood sample.
      Its wide applicability and potential importance will possibly lead to increasing
      clinical impact in the near future. However, large prospective clinical studies
      are needed to validate and standardise any tests for DNA or RNA alteration in
      plasma or serum of high risk individuals or patients with established lung
      cancer.

PMID- 15949586
TI  - Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant
      chemotherapy: results of a meta-analysis of the literature.
AB  - The recent publication of many randomised trials about (neo)adjuvant chemotherapy
      in resectable non-small cell lung cancer (NSCLC) has prompted our group to update
      a prior meta-analysis of the literature. Randomised studies published in French
      and English between 1965 and June 2004 were included in this analysis. A
      qualitative assessment of each trial was first performed using the European lung
      cancer working party (ELCWP) and the Chalmers' scales. In absence of
      statistically significant quality difference between positive and negative
      trials, a quantitative aggregation (meta-analysis) of the individual results was
      performed. Two trials for which data were available on ASCO virtual meeting
      website were also included in the meta-analysis. Twenty-five studies eligible for
      this analysis assessed chemotherapy as induction (n = 6) or adjuvant to surgery
      (n = 19). No quality difference was detected between positive and negative trials
      according to the two scores, whatever all trials were combined or only adjuvant
      chemotherapy studies were considered. The overall meta-analysis showed that the
      hazard ratio (HR) of the combined results was 0.66 (95% CI 0.48-0.93) in favour
      of the addition of induction chemotherapy to a standard surgical procedure and
      0.84 (95% CI 0.78-0.89) in favour of adjuvant chemotherapy. The effect was
      significant for adjuvant chemotherapy in stages I and II with a HR of 0.88 (95%
      CI 0.83-0.94). It was not statistically significant in stage III although the
      trend was in favour of chemotherapy whatever adjuvant (HR = 0.85; 95% CI 0.69
      1.04) or (neo)adjuvant (HR = 0.65; 95% CI 0.41-1.04) chemotherapy was tested. In
      conclusion, our meta-analysis shows the efficacy of adjuvant chemotherapy in
      stages I and II resected NSCLC. More data are needed to confirm such a role for
      induction chemotherapy. Further trials should separate stage III disease from
      earlier stages.

PMID- 15949587
TI  - Complete resection in lung cancer surgery: proposed definition.
AB  - OBJECTIVE: To propose an internationally accepted definition of complete
      resection in lung cancer surgery. MATERIAL AND METHODS: The International
      Association for the Study of Lung Cancer (IASLC) Staging Committee created the
      Complete Resection Subcommittee in 2001 to work on an international definition of
      complete resection in lung cancer surgery. The previous definitions of complete
      resection and the rules of the International Union Against Cancer regarding the
      TNM residual tumor classification, together with a thorough review of the
      pertinent literature, and the input of the members of the IASLC Staging Committee
      were considered in order to get an international consensus on the definition of
      complete resection in lung cancer surgery. RESULTS: Complete resection requires
      all of the following: free resection margins proved microscopically; systematic
      nodal dissection or lobe-specific systematic nodal dissection; no extracapsular
      nodal extension of the tumor; and the highest mediastinal node removed must be
      negative. Whenever there is involvement of resection margins, extracapsular nodal
      extension, unremoved positive lymph nodes or positive pleural or pericardial
      effusions, the resection is defined as incomplete. When the resection margins are
      free and no residual tumor is left, but the resection does not fulfill the
      criteria for complete resection, there is carcinoma in situ at the bronchial
      margin or positive pleural lavage cytology, the term uncertain resection is
      proposed. CONCLUSION: The proposed definitions of complete, incomplete and
      uncertain resections are clear and reproducible in an international setting to
      study their prognostic impact prospectively.

PMID- 15949588
TI  - NNK-induced hamster lung adenocarcinomas over-express beta2-adrenergic and EGFR
      signaling pathways.
AB  - Pulmonary adenocarcinoma (PAC) is the most common type of human lung cancer. A
      diagnosis of PAC, history of non-smoking and presence of mutations in the EGFR
      are predictive factors for responsiveness of lung cancer to EGFR-specific
      tyrosine kinase inhibitors. Unfortunately, less than 50% of PAC cases demonstrate
      this mutation-based responsiveness. Our immunohistochemical analysis of NNK
      induced PAC in hamsters demonstrates the simultaneous over-expression of a beta2
      adrenergic receptor pathway, including PKA, cAMP, CREB and phosphorylated CREB
      and of an EGFR pathway, including over-expression of EGFR-specific phosphorylated
      tyrosine kinase, Raf-1 and ERK1/2 and their phosphorylated forms. These findings
      implicate, for the first time, PKA/CREB-mediated signaling in the development and
      regulation of any type of lung cancer. In light of reports that NNK acts as a
      beta-adrenergic agonist and that beta-blockers inhibit the growth of PAC of Clara
      cell lineage in the NNK hamster model and in human cancer cell lines from
      smokers, our current data suggest transactivation of the EGFR pathway via beta
      adrenergic signaling as a novel regulatory mechanism in a subpopulation of PACs
      in smokers. Taken together, these data point to PKA/CREB as novel targets for the
      development of cancer therapeutics for PAC patients non-responsive to EGFR
      specific tyrosine kinase inhibitors.

PMID- 15949589
TI  - Role of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine against non
      small cell lung cancer--in correlation with the tumoral expression of thymidylate
      synthase and dihydropyrimidine dehydrogenase.
AB  - 5-Fluorouracil (5-FU) and its derivatives have been used worldwide for the
      treatment of several malignancies in solid organs. The effectiveness of these
      drugs is well proven in gastrointestinal malignancy, and has been reported upon
      the inverse correlation with the tumoral expression of dihydropyrimidine
      dehydrogenase (DPD). However, the significance of DPD expression in 5-FU based
      chemotherapy has not been well investigated in non-small cell lung cancer
      (NSCLC). We examined enzymatic activities and immunohistochemical expression of
      thymidylate synthase (TS) and DPD in 84 cases of NSCLC. In vitro sensitivity for
      5-FU was tested in 53 cases of them to evaluate these predictive values for
      effectiveness of 5-FU. Efficacy of 5-chloro-2,4-dihydroxypyridine (CDHP), potent
      DPD inhibitor, was also examined in 27 cases of them. There was a reversal
      correlation between protein expression of DPD and sensitivity to 5-FU (r = -0.65;
      p < 0.001). Six (33.3%) of 18 cases with strong expression of DPD showed 10% or
      more increment of the anti-tumor effect by adding CDHP to 5-FU. DPD inhibitory
      fluoropyrimidine and examination of the tumoral expression of DPD might be a
      promising chemotherapeutic strategy in NSCLC.

PMID- 15949590
TI  - Expression of endoplasmic reticulum molecular chaperone Grp78 in human lung
      cancer and its clinical significance.
AB  - All eukaryotic cells respond to the accumulation of unfolded proteins in the
      endoplasmic reticulum (ER) by signaling an adaptive pathway termed the unfolded
      protein response (UPR). Glucose-regulated protein (Grp) 78 is a molecular
      chaperone involved in the UPR. The aim of this study was to detect Grp78
      expression in lung cancer using immunohistochemical (IHC) staining, and also to
      evaluate the relationship between the Grp78 expression level and the prognosis of
      patients with lung cancer. We used immunohistochemistry to analyze the protein
      expression of Grp78 in paraffin-embedded tumor samples from 132 well
      characterized lung cancer patients and compared the expression level of Grp78,
      clinical variables and survival outcome. A positive expression of Grp78 was
      detected in the cytoplasm of tumor cells in 88 of the 132 patients (66.7%) with
      lung cancer. No significant difference was observed between the Grp78 expression
      and the gender, age at operation, histological type, pathologic stage, pathologic
      T status, and pathologic N status. Lung cancer patients with a positive Grp78
      expression tended to show a better prognosis than those with a negative Grp78
      expression. In addition, a multivariate analysis of the clinicopathologic
      characteristics of lung cancer indicated a positive expression of Grp78 to be a
      significant factor for predicting a favorable prognosis (p < 0.001, risk ratio =
      2.35). A positive expression of Grp78 may thus be a useful marker for predicting
      a favorable prognosis in patients undergoing a resection of lung cancer. The ER
      stress pathway mediated by Grp78 may therefore be responsible for controlling the
      growth of lung cancer cells.

PMID- 15949591
TI  - Smoking history before surgery and prognosis in patients with stage IA non-small
      cell lung cancer--a multicenter study.
AB  - The prognosis of lung cancer patients with surgically resected non-small-cell
      lung cancer (NSCLC) can be predicted generally from age, sex, histologic type,
      stage at diagnosis, and additional treatment. Nine studies have reported that a
      history of smoking before diagnosis influences the prognosis of the disease in
      lung cancer patients. In this study, a total of 3082 patients who underwent
      surgery and were diagnosed with primary pathological stage IA NSCLC at 36
      national hospitals from 1982 to 1997 were analyzed for the effect of smoking on
      survival. Smoking history and other factors influencing either the overall
      survival or the disease-specific survival rates of patients were estimated with
      the Cox proportional hazards model. Multivariate analysis demonstrated
      significant associations between overall survival and age (P < 0.0001), sex (P =
      0.0002), and performance status (PS) (P < 0.0001). Disease-specific survival was
      associated with age (P = 0.0063), sex (0.00161), and PS (P = 0.0029). In males,
      disease-specific survival was associated with age (P = 0.0120), PS (P = 0.0022),
      and pack-years (number of cigarette packs per day, and years of smoking) (P =
      0.0463). These results indicate that smoking history (pack-years) is important
      clinical prognostic factor in estimating disease-specific survival, in male
      patients with stage IA primary NSCLC that has been surgically resected.

PMID- 15949592
TI  - Serum levels of Magic Roundabout protein in patients with advanced non-small cell
      lung cancer (NSCLC).
AB  - BACKGROUND: Magic Roundabout (MR; ROBO 4) is a recently discovered gene which
      encodes a protein that derived its name form the structural homology with the
      roundabout family of genes. Genes of the roundabout family comprise neuronal
      specific cell surface receptors that are involved in axon guidance. MR in
      contrast showed endothelial specificity in vitro and in vivo using
      immunohistochemistry and in situ hybridisation. The putative role of MR as an
      endothelial analogue of Roundabout in angiogenesis makes it an attractive target
      for anti-angiogenic cancer therapy. PATIENTS AND METHODS: Using specific
      antibodies against MR peptide, we screened pretreatment sera from 193 patients
      with advanced non-small cell lung cancer (NSCLC) for MR-protein levels. RESULTS:
      Patients with serum levels of MR-protein lower than median (E(450 nm) = 0.652)
      had a median survival of 41.0 weeks whereas those with a higher serum level had a
      considerably shorter median survival of 32.4 weeks (P = 0.05). The pretreatment
      serum level of MR-protein achieved no significance in a univariate Cox regression
      analysis. CONCLUSIONS: This is the first study to present clinical data that link
      MR expression with outcome in patients with NSCLC, whether the correlation of
      pretreatment serum levels of MR and survival can be attributed to MR dependent
      angiogenesis remains to be investigated.

PMID- 15949593
TI  - Is voluntary vitamin and mineral supplementation associated with better outcome
      in non-small cell lung cancer patients? Results from the Mayo Clinic lung cancer
      cohort.
AB  - BACKGROUND: Some previous studies report that 80% of cancer patients take
      multivitamin and/or mineral supplements. To our knowledge, the consequences of
      such self-directed supplementation have not been examined previously in non-small
      cell lung cancer (NSCLC) patients. The goal of this study was to determine
      whether vitamin/mineral supplementation is associated with improved survival and
      quality of life in a cohort of NSCLC patients. METHODS: NSCLC patients or their
      proxies who responded to a questionnaire on vitamin/mineral use were assessed for
      survival and quality of life. RESULTS: A total of 1129 patients or their proxies
      responded to a vitamin/mineral questionnaire. Seven hundred and fourteen were
      vitamin/mineral users of either multivitamins or other specific vitamin/mineral
      supplements, and the rest non-users. Median survival was 4.3 years versus 2.0
      years for vitamin/mineral users and non-users, respectively. A Cox proportional
      hazards model showed a relative risk of death of 0.74 (95% confidence interval
      (CI): 0.44, 0.65) (p < 0.01) in favor of vitamin/mineral use after adjustment for
      multiple prognostic factors, including tumor stage. The Lung Cancer Symptom Scale
      (LCSS) showed better quality of life among vitamin/mineral users (mean difference
      in score of 3 (95% CI: 0.8, 5.1) (p < 0.01); and after adjusting for related
      variables, there remained a trend in favor of vitamin/mineral use mean difference
      1.8 (95% CI: 0.2, 3.9) (p = 0.08). CONCLUSIONS: Vitamin/mineral supplementation
      is associated with better survival and quality of life in this cohort of NSCLC
      patients. Future prospective clinical trials should focus on the role of such
      supplements in patients with NSCLC.

PMID- 15949594
TI  - Postoperative adjuvant cisplatin, vindesine, plus uracil-tegafur chemotherapy
      increased survival of patients with completely resected p-stage I non-small cell
      lung cancer.
AB  - PURPOSE: To evaluate the efficacy of postoperative adjuvant chemotherapy for
      completely resected p-stage I non-small cell lung cancer (NSCLC). MATERIALS AND
      METHODS: Patients who underwent complete resection with lymph node dissection for
      p-stage I NSCLC (T1N0, T2N0, adenocarcinoma or squamous cell carcinoma, were
      eligible. After surgery, 150 patients were stratified according to tumor size and
      histologic type, and then randomly assigned to 1 of 3 groups (50 patients each
      group): surgery alone (control group), surgery with chemotherapy; PVU group (2
      courses of cisplatin 80 mg/m2, i.v. x 1 (day 1), vindesine 3 mg/m2, i.v. x 1
      (days 1 and 8) and UFT 400 mg/day, p.o. for a period of 2 years), and UFT group
      (UFT 400 mg/day, p.o. for 2 years). RESULTS: The 5-year survival rates of the PVU
      group, the UFT group, and the control group were 87.9, 67.7, and 66.3%,
      respectively. The difference in 5-year survival between the PVU group and the
      control group was statistically significant (p = 0.045, log rank). The 5-year
      disease-free survival rate of the PVU group (81.1%) was also significantly better
      than that of the control group (66.5%) (p = 0.042, log rank). According to
      multivariate analysis using Cox's proportional hazard model, the only
      significantly positive factor on outcome was PVU chemotherapy after surgery.
      CONCLUSION: Postoperative PVU chemotherapy is effective for Japanese patients
      with completely resected p-stage I NSCLC.

PMID- 15949595
TI  - Metabolic (FDG-PET) response after radical radiotherapy/chemoradiotherapy for non
      small cell lung cancer correlates with patterns of failure.
AB  - BACKGROUND: We previously reported that F-18 fluorodeoxyglucose (FDG) positron
      emission tomography (PET) response correlated strongly with survival after
      radical radiotherapy (RT)/chemoradiotherapy for non-small cell lung cancer
      (NSCLC). PET-response, survival and patterns of failure data are presented with
      long-term follow-up. METHODS: Pre- and post-treatment FDG-PET scans were
      performed for 88 patients after concurrent platinum-based radical chemo/RT (n =
      73) or radical RT alone (n = 15). PET responses were prospectively assessed as
      either complete metabolic response (CMR), partial metabolic response (PMR),
      stable metabolic disease (SMD), or progressive metabolic disease (PMD). RESULTS:
      RT was 60 Gy in 30 fractions in 6 weeks. Follow-up PET was performed at a median
      of 70 days after treatment. PET responses were: CMR, n = 40 (45%); PMR, n = 32
      (36%); SMD, n = 5 (6%) and PMD 11 (13%). Estimated median survival after follow
      up PET was 23 months; median follow-up duration 35 months. One and 2 year
      survival after follow-up PET was 68% and 45%, respectively. Median survival for
      CMR and non-CMR patients was 31 and 11 months, respectively (p = 0.0001). One
      year survival for CMR and non-CMR patients was 93% and 47%, respectively and 2
      years survival was 62% and 30%, respectively. Excluding PMD patients, non-CMR
      patients had higher rates of local failure (HR 2.15, p = 0.009) and distant
      metastasis (HR 2.05, p = 0.041) than CMR patients. By last follow-up, 20 of 40 CR
      patients (50%) had PMD, with local failure (n = 8), distant metastasis (n = 2) or
      both (n = 10). CONCLUSIONS: Attainment of CMR after radical RT/chemoRT for NSCLC
      bestows superior freedom from local and distant relapse; late local relapse is
      common.

PMID- 15949596
TI  - Does the incidence and outcome of brain metastases in locally advanced non-small
      cell lung cancer justify prophylactic cranial irradiation or early detection?
AB  - OBJECTIVE: The radical treatment of locally advanced non-small cell lung cancer
      (LA-NSCLC) currently involves combined modality therapy (CMT) with the use of
      chemotherapy in addition to radiation therapy and/or surgery. Chemotherapy has
      been shown to improve survival, but does not alter brain relapse. We reviewed the
      outcomes of Stage IIIA and IIIB LA-NSCLC patients treated with CMT at our
      institution. We assessed the incidence of brain metastases and the management and
      outcome of these patients. METHODS: Using our radiation-planning database (RSTS),
      we identified 230 consecutive patients from the years 1999 and 2000 who received
      radical radiation therapy to the lung. Extracting data from the chart, we
      identified 83 patients who were treated radically with chemotherapy, radiation
      and possibly surgery. These patients form the basis of this study. RESULTS: At 2
      years, the actuarial rates for any brain failure, first failure in the brain and
      sole failure in the brain were 34.2%, 24.6% and 11.0%, respectively. Age was the
      only factor among sex, histology, stage, weight loss and the timing of
      chemotherapy and radiation that predicted for an increased risk of first failure
      in the brain. Patients less than age 60 had a risk of 25.6% versus 11.4% for
      those greater than 60 (p = 0.022). Among the patients who failed first in the
      brain, those who had aggressive management of their brain metastases with
      surgical resection in addition to whole brain radiotherapy had a median survival
      of 26.3 months compared with 3.3 months for those treated with palliative whole
      brain radiotherapy alone. CONCLUSION: Brain metastases are common in patients
      with LA-NSCLC treated with CMT. These patients may benefit from either
      prophylactic cranial irradiation or early detection and aggressive treatment of
      brain metastases.

PMID- 15949597
TI  - Sequential therapy with Vinorelbine followed by Gemcitabine in patients with
      metastatic non small cell lung cancer (NSCLC), performance status (PS) 2, or
      elderly with comorbidities--a multicenter phase II trial.
AB  - BACKGROUND: High risk patients with metastatic non small cell lung cancer (NSCLC)
      including patients with performance status (PS) 2 or elderly with comorbidities
      do poorly on combination chemotherapy regimens. We evaluated a sequential
      treatment with Vinorelbine followed by Gemcitabine to determine its effect on
      survival and the toxicity in this patient population. METHODS: Forty-two
      evaluable patients, median age 75, 21 patients with PS 2 and 21 patients with PS
      0 or 1, 37 patients with stage IV and five patients with stage III B NSCLC
      entered the trial. They received Vinorelbine 30 mg/m2, i.v., on days 1+8 every 3
      weeks followed by Gemcitabine 1000 mg/m2, i.v., on days 1+8 every 3 weeks, each
      for two cycles for stable disease or one cycle after best response. Then stable
      patients continued until progressive disease on Vinorelbine or Gemcitabine
      according to the patient's preference. RESULTS: A total of 126 cycles of
      Vinorelbine were administered to 42 patients, median of three cycles per patient
      and 74 cycles of Gemcitabine, median of 1.0 cycle per patient. Sixteen patients
      (38%) achieved PR, 11 patients on Vinorelbine, 5 patients on Gemcitabine; 12
      patients (26%) had stable disease, 7 patients on Vinorelbine, 5 patients on
      Gemcitabine. Of 24 patients with progressive disease on Vinorelbine, 3 patients
      (12.5%) responded to Gemcitabine. Median time-to-first progression was 3.5
      months, median survival was 8 months, 1-year survival was 12 patients (28.5%). No
      grade 3 or 4 toxicities were reported. CONCLUSION: This sequential treatment
      offers excellent palliative treatment with minimal toxicity for high-risk
      patients with metastatic NSCLC.

PMID- 15949598
TI  - Novel effects of gefitinib on mucin production in bronchioloalveolar carcinoma;
      two case reports.
AB  - Two Japanese females complained of cough and bronchorrhea for which chest
      radiographs showed infiltrate in the lungs. The patients were subsequently
      diagnosed as having bronchioloalveolar carcinoma by transbronchial lung biopsy.
      After receiving systemic chemotherapy, their symptoms were slightly improved. A
      few months later, their bronchorrhea and dyspnea worsened, and they were then
      treated with gefitinib, a selective epidermal growth factor receptor tyrosine
      kinase inhibitor. Bronchorrhea and dyspnea were improved within 24 h after
      treatment with gefitinib where the improvement was evident after 6 h for one
      patient and 24 h for the other patient. Thereafter, their radiological findings
      showed gradual improvement. Rapid relief of bronchorrhea preceded the improvement
      seen by the radiological findings. These observations suggest that gefitinib may
      inhibit mucin production as well as exert anti-proliferative activity against
      bronchioloalveolar carcinoma.

PMID- 15949599
TI  - Multivariate analysis of factors predictive of brain metastases in localised non
      small call lung carcinoma.

PMID- 15949601
TI  - Do we need a size-based subclassification for lung cancers larger than 3 cm?

PMID- 15949603
TI  - Smoking status and adenocarcinoma histology may explain an improved survival in
      the female non-small cell lung cancer patients.

PMID- 15949605
TI  - Effects of a reactive barrier and aquifer geology on metal distribution and
      mobility in a mine drainage impacted aquifer.
AB  - The Nickel Rim aquifer has been impacted for five decades by a metal-rich plume
      generated from the Nickel Rim mine tailings impoundment. Metals released by the
      oxidation of pyrrhotite in the unsaturated zone of the tailings migrate into the
      downgradient aquifer, affecting both the groundwater and the aquifer solids. A
      reactive barrier has been installed in the aquifer to remove sulfate and metals
      from the groundwater. The effect of the reactive barrier on metal concentrations
      in the aquifer solids has not previously been studied. In this study, a series of
      selective extraction procedures was applied to cores of aquifer sediment, to
      ascertain the distribution of metals among various solid phases present in the
      aquifer. Extraction results were combined with groundwater chemistry, geochemical
      modelling and solid-phase microanalyses, to assess the potential mobility of
      metals under changing geochemical conditions. Reactions within the reactive
      barrier caused an increase in the solid-phase carbonate content downgradient from
      the barrier. The concentrations of poorly crystalline, oxidized phases of Mn and
      Fe, as well as concentrations of Cr(III) associated with oxidized Fe, and poorly
      crystalline Zn, are lower downgradient from the barrier, whereas total solid
      phase metal concentrations remain constant. Iron and Mn accumulate as oxidized,
      easily extractable forms in a peat layer overlying the aquifer. Although these
      oxides may buffer reducing plumes, they also have the potential to release metals
      to the groundwater, should a reduced condition be imposed on the aquifer by
      remedial actions.

PMID- 15949606
TI  - Redistribution of contaminants by a fluctuating water table in a micro-porous,
      double-porosity aquifer: field observations and model simulations.
AB  - Large seasonal fluctuations of the water table are characteristic of aquifers
      with a low specific yield, including those fractured, double-porosity aquifers
      that have significant matrix porosity containing virtually immobile porewater,
      such as the Chalk of northern Europe. Where these aquifers are contaminated, a
      strong relationship between water table elevation and contaminant concentration
      in groundwater is commonly observed, of significance to the assessment,
      monitoring, and remediation of contaminated groundwater. To examine the processes
      governing contaminant redistribution by a fluctuating water table within the
      'seasonally unsaturated zone', or SUZ, profiles of porewater solute
      concentrations have been established at a contaminated site in southern England.
      These profiles document the contaminant distribution in porewater of the Chalk
      matrix over the SUZ at a greater level of detail than recorded previously. A
      novel double-porosity solute transport code has been developed to simulate the
      evolution of the SUZ matrix porewater contaminant profiles, given a fluctuating
      water table, when the groundwater is initially contaminated and the SUZ is
      initially free of contamination. The model is simply characterised by: the matrix
      fracture porosity ratio, the matrix block geometry, and a characteristic
      diffusion time. De-saturation and re-saturation of fractures is handled by a new
      approximation method. Contaminant accumulates in the upper levels of the SUZ,
      where it is less accessible to mobile groundwater, and acts as a persistent
      secondary source of contamination once the original source of contamination has
      been removed or has become depleted. The 'SUZ process' first attenuates the
      progress of contaminants in groundwater, and subsequently controls the slow
      release of contamination back to the mobile groundwater, thus prolonging the
      duration of groundwater contamination by many years. The SUZ process should
      operate in any fractured, micro-porous lithology e.g. fractured clays and
      mudstones, making this approach widely applicable.

PMID- 15949607
TI  - Optimized method for dissolved hydrogen sampling in groundwater.
AB  - Dissolved hydrogen concentrations are used to characterize redox conditions of
      contaminated aquifers. The currently accepted and recommended bubble strip method
      for hydrogen sampling (Wiedemeier et al., 1998) requires relatively long sampling
      times and immediate field analysis. In this study we present methods for
      optimized sampling and for sample storage. The bubble strip sampling method was
      examined for various flow rates, bubble sizes (headspace volume in the sampling
      bulb) and two different H2 concentrations. The results were compared to a
      theoretical equilibration model. Turbulent flow in the sampling bulb was
      optimized for gas transfer by reducing the inlet diameter. Extraction with a 5 mL
      headspace volume and flow rates higher than 100 mL/min resulted in 95-100%
      equilibrium within 10-15 min. In order to investigate the storage of samples from
      the gas sampling bulb gas samples were kept in headspace vials for varying
      periods. Hydrogen samples (4.5 ppmv, corresponding to 3.5 nM in liquid phase)
      could be stored up to 48 h and 72 h with a recovery rate of 100.1+/-2.6% and
      94.6+/-3.2%, respectively. These results are promising and prove the possibility
      of storage for 2-3 days before laboratory analysis. The optimized method was
      tested at a field site contaminated with chlorinated solvents. Duplicate gas
      samples were stored in headspace vials and analyzed after 24 h. Concentrations
      were measured in the range of 2.5-8.0 nM corresponding to known concentrations in
      reduced aquifers.

PMID- 15949608
TI  - Numerical simulations of radon as an in situ partitioning tracer for quantifying
      NAPL contamination using push-pull tests.
AB  - Presented here is a reanalysis of results previously presented by [Davis, B.M.,
      Istok, J.D., Semprini, L., 2002. Push-pull partitioning tracer tests using radon
      222 to quantify non-aqueous phase liquid contamination. J. Contam. Hydrol. 58,
      129-146] of push-pull tests using radon as a naturally occurring partitioning
      tracer for evaluating NAPL contamination. In a push-pull test where radon-free
      water and bromide are injected, the presence of NAPL is manifested in greater
      dispersion of the radon breakthrough curve (BTC) relative to the bromide BTC
      during the extraction phase as a result of radon partitioning into the NAPL.
      Laboratory push-pull tests in a dense or DNAPL-contaminated physical aquifer
      model (PAM) indicated that the previously used modeling approach resulted in an
      overestimation of the DNAPL (trichloroethene) saturation (S(n)). The numerical
      simulations presented here investigated the influence of (1) initial radon
      concentrations, which vary as a function of S(n), and (2) heterogeneity in S(n)
      distribution within the radius of influence of the push-pull test. The
      simulations showed that these factors influence radon BTCs and resulting
      estimates of S(n). A revised method of interpreting radon BTCs is presented here,
      which takes into account initial radon concentrations and uses non-normalized
      radon BTCs. This revised method produces greater radon BTC sensitivity at small
      values of S(n) and was used to re-analyze the results from the PAM push-pull
      tests reported by Davis et al. The re-analysis resulted in a more accurate
      estimate of S(n) (1.8%) compared with the previously estimated value (7.4%). The
      revised method was then applied to results from a push-pull test conducted in a
      light or LNAPL-contaminated aquifer at a field site, resulting in a more accurate
      estimate of S(n) (4.1%) compared with a previously estimated value (13.6%). The
      revised method improves upon the efficacy of the radon push-pull test to estimate
      NAPL saturations. A limitation of the revised method is that 'background' radon
      concentrations from a non-contaminated well in the NAPL-contaminated aquifer are
      needed to accurately estimate NAPL saturation. The method has potential as a
      means of monitoring the progress of NAPL remediation.

PMID- 15949609
TI  - Scoping analyses of geochemical sealing of early cracks in a waste container and
      associated drip shield, Yucca Mountain, Nevada.
AB  - Early after final emplacement of the nuclear waste containers at the proposed
      Yucca Mountain, Nevada, high-level-waste repository, tiny cracks (less than 200
      microm wide, 1 to 2 cm deep, and a few centimeters long at most) could appear in
      the containers and in the drip shield protecting them. Modeling calculations were
      performed to understand how fast those cracks could be sealed. Under dripping
      conditions, they are expected to be bridged with water. If cracks are located in
      the drip shield, any further dripping on the waste containers located underneath
      will be limited. If cracks are located in a container, potentially harmful
      radionuclides could only travel by diffusion. In addition, water-bridged cracks
      will be sealed through at least two processes: precipitation of calcite with
      minor silica following evaporative concentration of the water residing in the
      cracks and continuous corrosion of the crack walls. The sealing rate is
      calculated as the intersection of the time of emergence of the cracks, the water
      dripping rate, and the decreasing evaporation rate. The evaporative driving force
      declines as short-lived radioactive elements, having given up much of the heat
      affecting the repository, are progressively depleted from the waste. Depending on
      the crack initiation time and environmental conditions, crack sealing varies from
      a few tens of years to a few thousand years. Because environmental conditions in
      the vicinity of the cracks and at the crack scale have not been produced, a
      parametric method scaling drift scale conditions is used.

PMID- 15949610
TI  - Modelling of sequential groundwater treatment with zero valent iron and granular
      activated carbon.
AB  - Multiple contaminant mixtures in groundwater may not efficiently be treated by a
      single technology if contaminants possess rather different properties with
      respect to sorptivity, solubility, and degradation potential. An obvious choice
      is to use sequenced units of the generally accepted treatment materials zero
      valent iron (ZVI) and granular activated carbon (GAC). However, as the results of
      this modelling study suggest, the required dimensions of both reactor units may
      strongly differ from those expected on the grounds of a contaminant-specific
      design. This is revealed by performing an analysis for a broad spectrum of design
      alternatives through numerical experiments for selected patterns of contaminant
      mixtures consisting of monochlorobenzene, tetrachloroethylene, trichloroethylene
      (TCE), cis-1,2-dichloroethylene (cis-DCE), and vinyl chloride (VC). It is shown
      that efficient treatment can be achieved only if competitive sorption effects in
      the GAC unit as well as the formation of intermediate products in the ZVI unit
      are carefully taken into account. Cost-optimal designs turned out to vary
      extremely depending on the prevailing conditions concerning contaminant
      concentrations, branching ratios, and unit costs of both reactor materials. Where
      VC is the critical contaminant, due to high initial concentration or extensive
      production as an intermediate, two options are cost-effective: an oversized ZVI
      unit with an oversized GAC unit or a pure GAC reactor.

PMID- 15949611
TI  - Clinician-led surgical site infection surveillance of orthopaedic procedures: a
      UK multi-centre pilot study.
AB  - The UK Department of Health established the Healthcare-associated Infection (HAI)
      Surveillance Steering Group in 2000 to develop a strategy for implementing a
      national programme for HAI surveillance in National Health Service trusts. A
      subgroup of this committee examined the surveillance of surgical site infections
      following orthopaedic surgery. This group oversaw a pilot scheme that was set up
      in 12 hospitals around the UK to explore the feasibility of implementing a system
      of surveillance that engaged clinical staff in its operation, provided a process
      for continuous data collection and could be maintained as part of routine
      hospital operation over time. A minimum data set was established by the subgroup,
      and Centers for Disease Control and Prevention (CDC) definitions of infection
      were used. By March 2003, the surveillance had been undertaken continuously in 11
      sites for one to two years, depending on the date of implementation. Only one
      hospital had ceased data collection. The information was collected mainly by
      clinical staff, with support and co-ordination usually provided by infection
      control teams. Data on more than 5400 procedures were available for analysis for
      four core procedures: arthroplasty of the hip and knee; hemi-arthroplasty of the
      hip; and internal fixation of trochanteric fractures of the femur. The data set
      permitted the calculation of risk-adjusted rates, allowing comparisons between
      hospitals and within a hospital over time. The methodology enhanced clinical
      ownership of the surveillance process, re-inforced infection control as the
      responsibility of all staff, and provided timely feedback and local data
      analysis. The use of CDC definitions permitted international comparisons of the
      data.

PMID- 15949612
TI  - An audit of the use of isolation facilities in a UK National Health Service
      trust.
AB  - To aid the ongoing battle against hospital-acquired infection in the UK, all
      acute National Health Service (NHS) trusts should have audit data about how
      dedicated isolation beds within the trust are being used. In a previously
      published audit, we demonstrated that one-third of patients admitted to a
      dedicated isolation room in Tayside were not thought to be an infection risk by
      experienced healthcare staff. Since this audit, Tayside's isolation facilities
      have moved from a small peripheral 'fever' hospital to a large central teaching
      hospital site. At the time of this move, and using the above audit data, we
      designed and implemented a guideline for general practitioners and hospital
      doctors regarding the admission of patients to an isolation bed. The aim of this
      study was to compare the use of isolation beds before and after the move to the
      new facilities, which we anticipated would increase the demand for isolation. The
      results show that by all three criteria used, the utilization of isolation beds
      has deteriorated following the move, mainly due to the increased admission of
      general medical 'boarders' and low-risk infection patients. At a time when
      hospital-acquired infections are increasing, NHS trusts should ensure that
      dedicated isolation beds are used appropriately.

PMID- 15949613
TI  - Hand hygiene posters: motivators or mixed messages?
AB  - Poster campaigns regarding hand hygiene are commonly used by infection control
      teams to improve practice, yet little is known of the extent to which they are
      based on established theory or research. This study reports on the content
      analysis of hand hygiene posters (N=69) and their messages (N=75) using message
      framing theory. The results showed that posters seldom drew on knowledge about
      effective ways to frame messages. Frequently, they simply conveyed information
      'telling' rather than 'selling' and some of this was confusing. Most posters were
      not designed to motivate, and some conveyed mixed messages. Few used fear
      appeals. Hand hygiene posters could have a greater impact if principles of
      message framing were utilized in their design. Suggestions for gain-framed
      messages are offered, but these need to be tested empirically.

PMID- 15949614
TI  - Residual antibiotics in allograft heart valve tissue samples following antibiotic
      disinfection.
AB  - Antibiotics are routinely used for the decontamination of allograft heart valves.
      To monitor the efficacy of this process, samples of tissue are sent for
      microbiological analysis. This investigation was undertaken to determine residual
      antibiotic concentrations in decontaminated tissue and to assess the likely
      inhibitory effect on microbiological cultures. After a typical decontamination
      protocol, both gentamicin and vancomycin were present in all tissue samples and
      the majority of enrichment broths at concentrations sufficient to inhibit most
      bacteria. The data presented indicate that protocols used by heart valve banks
      and associated microbiology laboratories should be reviewed, and support the use
      of predecontamination cultures to identify particularly virulent micro-organisms.

PMID- 15949615
TI  - Non-touch fittings in hospitals: a procedure to eradicate Pseudomonas aeruginosa
      contamination.
AB  - Non-touch taps, now common in hospitals, can easily be contaminated with
      Pseudomonas aeruginosa. We report our experience with 87 non-touch taps in a
      newly built wing of our teaching hospital contaminated with P. aeruginosa from
      the central pipe water system. Serotyping and genotyping of strains revealed
      genetic diversity of isolates, but also showed that major clones were able to
      persist for long periods of time in non-touch taps despite chlorination. It is
      notoriously difficult to decontaminate such taps with biocides and disinfectants.
      We describe an easy and economical procedure for the eradication of P. aeruginosa
      contamination from non-touch taps that does not require their removal.

PMID- 15949616
TI  - Epidemiological analysis of carbapenem-sensitive and -resistant Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa with decreased levels of meropenem susceptibility were
      identified in the Royal Infirmary Edinburgh in 2002. Within the affected group of
      patients, none had meropenem-resistant P. aeruginosa when they arrived in the
      intensive care unit (ICU). Seven isolates from the ICU were collected five months
      after the decreased susceptibility to meropenem was identified. In order to
      investigate if resistance was a problem in P. aeruginosa throughout Edinburgh,
      both in hospital- and community-acquired isolates, a prospective study was
      performed. The susceptibilities of 104 P. aeruginosa to imipenem, meropenem,
      ceftazidime, piperacillin/tazobactam and ciprofloxacin were investigated.
      Meropenem had the highest activity against these isolates and the lowest MIC(90)
      (2 mg/L), followed by imipenem (4 mg/L), ciprofloxacin (8 mg/L),
      piperacillin/tazobactam (16 mg/L) and ceftazidime (32 mg/L). These isolates were
      also analysed genotypically by pulsed-field gel electrophoresis. Five of the
      seven ICU isolates were identified, one isolate was 98% similar and the other was
      85% similar to the ICU isolates. One isolate from the prospective study had
      approximately 90% genotype similarity to the six ICU isolates with >/=98%
      similarity. There was no clonality within the strains from the prospective study
      and clusters with >90% similarity comprised at five or less isolates. Isolates
      with the same resistance patterns did not necessarily have the same genotypic
      profile. Strains isolated from different patients on the same day were also not
      necessarily related. The conclusions of this study were that while the seven ICU
      isolates were clonal or highly related, they were not widespread throughout
      Edinburgh and the P. aeruginosa within Edinburgh were highly varied.

PMID- 15949617
TI  - Antimicrobial activity of ultrasonic cleaners.
AB  - This study assessed the antimicrobial activity of two cleaning solutions and tap
      water after varying periods of use in one ultrasonic cleaner. Testing involved
      filling the cleaner's tank and a centred glass beaker with the same test
      solution. An aluminium foil strip test first determined that no significant
      differences in cavitational activity existed inside the beaker compared with
      outside. Standardized solutions of Staphylococcus aureus, Pseudomonas aeruginosa
      and Salmonella choleraesuis were left at room temperature for 10 min. Aliquots
      were exposed to both cleaning solution and ultrasonic action. Unused test
      solution was removed from the tank, filter-sterilized, mixed with bacterial
      suspension and placed into a sterile beaker. Cleaning was allowed for 10 min. The
      beaker was removed and its contents examined. The tank was allowed to cool for 30
      min and the process was repeated four times. The entire experimental set was
      repeated once. Exposure to test solution alone in all but one case produced
      reductions in bacterial numbers from initial >/=2 x 10(9) by 19.9-52.6%.
      Application of both chemical exposure and ultrasonic cleaning produced greater
      bacterial kill (46.4-99.7% reductions). However, kill became less effective on
      repeated use of a commercial cleaning solution. Reduction was highest when fresh
      ultrasonic cleaning solutions were used. In no case did complete sterilization
      occur. As well as removing adherent material, ultrasonic cleaning may also
      markedly reduce the number of viable organisms present.

PMID- 15949618
TI  - Does hospital work constitute a risk factor for Helicobacter pylori infection?
AB  - The aim of this study was to assess whether clinical work constitutes a risk
      factor for Helicobacter pylori infection among employees in hospitals. The
      prevalence of H. pylori infection was analysed in 249 individuals employed in a
      university teaching hospital according to three categories of hospital workers:
      (A) personnel from gastrointestinal endoscopy units (N=92); (B) personnel from
      other hospital units with direct patient contact (N=105); and (C) staff from
      laboratories and other units with no direct patient contact (N=52). Stool samples
      from each subject were examined with a validated enzyme-linked immunosorbent
      assay for the presence of H. pylori antigens. A questionnaire inquiring about
      sociodemographic and occupational characteristics was completed by each
      participant. The prevalence of H. pylori infection was 37.0% in group A, 35.2% in
      group B and 19.2% in group C (P<0.05). Among the different healthcare categories,
      nurses had a significant higher prevalence of H. pylori infection (P<0.01). No
      significant association was found between the length of employment or exposure to
      oral and faecal secretions, and H. pylori infection. Hospital work involving
      direct patient contact seems to constitute a major risk factor for H. pylori
      infection compared with hospital work not involving direct patient contact.

PMID- 15949619
TI  - Epidemiological characteristics of occupational blood exposures of healthcare
      workers in a university hospital in South Korea for 10 years.
AB  - This study investigated the epidemiological characteristics of occupational blood
      exposures (OBEs) of healthcare workers (HCWs) in South Korea, and examined trends
      of OBEs after implementing blood exposure prevention (BEP) programmes. The study
      was conducted between 1 January 1992 and 31 December 2001 at a university
      affiliated acute care hospital in Seoul. The BEP programmes comprised in-service
      education, hepatitis B virus (HBV) vaccination, and postexposure evaluation and
      prophylaxis. From 959 reported cases of OBEs, the crude incidence density (ID)
      was 2.62 cases per 100 person-years. The major risk groups for OBEs were
      physicians (ID 4.34) and new employees. The major type of OBE was from sharps
      injuries, including needlesticks (94.0%). OBE cases occurred more frequently
      during the spring (36.4%). The frequency of the serological tests of anti
      hepatitis B surface antigen of HCWs changed significantly each year (P<0.05). The
      major serological risk for source patients was HBV (52.1%), but the risks for
      hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increased
      significantly each year (P<0.05). There were no seroconversion cases following
      OBEs among the tested HCWs. In summary, we established the epidemiological
      characteristics of OBEs in a South Korean university hospital, and reduced the
      risk of OBEs of major risk groups by BEP programmes. We also found an increase in
      the risk of HCV and HIV during the study period, suggesting that OBEs could be a
      serious threat to HCWs.

PMID- 15949620
TI  - Parasites in nosocomial diarrhoea: are they underestimated?
AB  - Nosocomial diarrhoea, defined as diarrhoea occurring more than 72 h after
      hospital admission, is reported to account for <1% of endemic nosocomial
      infections and 17% of epidemic nosocomial infections. The yield of diagnoses from
      stool cultures in nosocomial diarrhoea is low, and information regarding the role
      of parasites is limited. We conducted a study to determine the responsible
      bacterial and parasitological pathogens from nosocomial diarrhoea cases in our
      2000-bed tertiary care facility over a 16-month period. Of 226 patients,
      Clostridium difficile toxins A or B were present in 5.5%, giardia cysts and/or
      trophozoites in 4.4%, Blastocytis hominis in 4.4% and Cryptosporidium sp. in 0.5%
      of samples. In conclusion, parasites should be sought in nosocomial diarrhoea in
      endemic areas.

PMID- 15949621
TI  - Risk factors for CVC-related infections in ICUs: evaluation of time, type and
      number of cannulations.

PMID- 15949622
TI  - Decrease in Staphylococcus aureus surgical site infections following
      cardiovascular surgery.

PMID- 15949623
TI  - Does adherence to universal precautions correlate with the prevalence of blood
      borne infections?

PMID- 15949624
TI  - Vaccinated but not immunized: healthcare personnel in developing countries.

PMID- 15949625
TI  - SARS, emerging diseases, healthcare workers and respirators.

PMID- 15949626
TI  - Molecular modeling and docking simulations of scorpion toxins and related analogs
      on human SKCa2 and SKCa3 channels.
AB  - The small-conductance Ca2+-activated K+ (SKCa) channels modulate cytosolic Ca2+
      concentration in excitable and non-excitable tissues by regulating the membrane
      potential and are responsible of slow action potential after hyperpolarization
      that inhibits cell firing. Among these, human SKCa2 and SKCa3 channels differ in
      the pore region by only two residues: Ala331 and Asn367 (human small-conductance
      calcium-activated potassium channel, hSKCa2) instead of Val485 and His521
      (hSKCa3). To design highly selective blockers of hSKCa channels, a number of
      known hSKCa2 and/or hSKCa3-active peptides (i.e. scorpion toxins and analogs
      thereof) were analyzed for their interactions and selectivities toward these
      channels. Molecular models of hSKCa2 and hSKCa3 channels (S5-H5-S6 portion) were
      generated, and scorpion toxins/peptides of unsolved three-dimensional (3D)
      structures were modeled. Models of toxin-channel complexes were generated by the
      bimolecular complex generation with global evaluation, and ranking (BiGGER)
      docking software and selected by using a screening method of the docking
      solutions. A high degree of correlation was found to exist between docking
      energies and experimental Kd values of peptides that blocked hSKCa2 and/or hSKCa3
      channels, suggesting it could be appropriate to predict Kd values of other
      bioactive peptides. The best scoring complexes were also used to identify key
      residues of both interacting partners, indicating that such an approach should
      help the design of more active and/or selective peptide blockers of targeted ion
      channels.

PMID- 15949627
TI  - Catalytic effects of glycine on prebiotic divaline and diproline formation.
AB  - The catalytic effects of the simple amino acid glycine on the formation of
      diproline and divaline in the prebiotically relevant salt-induced peptide
      formation (SIPF) reaction was investigated in systems of different amino acid
      starting concentrations and using the two enantiomeric forms of the respective
      amino acid. Results show an improved applicability of the SIPF reaction to
      prebiotic conditions, especially at low amino acid concentrations, as presumably
      present in a primordial scenario, and indicate excellent conditions and resources
      for chemical evolution of peptides and proteins on the early earth. For valine,
      furthermore differences in catalytic yield increase are found indicating a chiral
      selectivity of the active copper complex of the reaction and showing a connection
      to previously found enantiomeric differences in complex formation constants with
      amino acids.

PMID- 15949629
TI  - Sesquin, a potent defensin-like antimicrobial peptide from ground beans with
      inhibitory activities toward tumor cells and HIV-1 reverse transcriptase.
AB  - An antifungal peptide with a molecular mass around 7 kDa and an N-terminal
      sequence highly homologous to defensin was isolated from ground beans (Vigna
      sesquipedalis cv. 'Ground Bean'). The peptide was adsorbed on Affi-gel blue gel
      and on Mono S. It exerted an antifungal action on Botrytis cinerea, Fusarium
      oxysporum and Mycosphaerella arachidicola; and an antibacterial action on
      Escherichia coli B, Proteus vulgaris, Mycobacterium phlei and Bacillus
      megaterium. The antimicrobial activity was inhibited in presence of the 5 mM
      CaCl2 and MgCl2, but no inhibition was observed in 5 mM NaCl. The peptide exerted
      antiproliferative activity toward breast cancer (MCF-7) cells and leukemia M1
      cells, this activity could not be inhibited by the ions mentioned above. It also
      exhibited some inhibitory activity toward human immunodeficiency virus-type 1
      reverse transcriptase.

PMID- 15949628
TI  - Antifungal activity of synthetic peptides derived from Impatiens balsamina
      antimicrobial peptides Ib-AMP1 and Ib-AMP4.
AB  - Seeds of Impatiens balsamina contain a set of related antimicrobial peptides (Ib
      AMPs). We have produced a synthetic variant of Ib-AMP1, oxidized to the bicyclic
      native conformation, which was fully active on yeast and fungal strains; and four
      linear 20-mer Ib-AMP variants, including two all-D forms. We show that the all-D
      variants are as active on yeast and fungal strains as native peptides. In
      addition, fungal growth inhibition nor salt-dependency of Ib-AMP4 could be
      improved by more than two-fold via replacement of amino acid residues by arginine
      or tryptophan. Native Ib-AMPs showed no hemolytic nor toxic activity up to a
      concentration of 100 microM. All these data demonstrate the potential of the
      native Ib-AMPs to combat fungal infections.

PMID- 15949630
TI  - Interaction of antimicrobial peptides with bacterial polysaccharides from lung
      pathogens.
AB  - The interaction of two cathelicidin antimicrobial peptides, LL-37 and SMAP-29,
      with three bacterial polysaccharides, respectively, produced by Pseudomonas
      aeruginosa, Burkholderia cepacia and Klebsiella pneumoniae, was investigated to
      identify possible mechanisms adopted by lung pathogens to escape the action of
      innate immunity effectors. In vitro assays indicated that the antibacterial
      activity of both peptides was inhibited to a variable extent by the three
      polysaccharides. Circular dichroism experiments showed that these induced an
      alpha-helical conformation in the two peptides, with the polysaccharides from K.
      pneumoniae and B. cepacia showing, respectively, the highest and the lowest
      effect. Fluorescence measurements also indicated the presence of peptide
      polysaccharide interactions. A model is proposed in which the binding of peptides
      to the polysaccharide molecules induces, at low polysaccharide to peptide ratios,
      a higher order of aggregation, due to peptide-peptide interactions. Overall,
      these results suggest that binding of the peptides by the polysaccharides
      produced by lung pathogens can contribute to the impairment of peptide-based
      innate defenses of airway surface.

PMID- 15949631
TI  - Peptides from the Plasmodium falciparum STEVOR putative protein bind with high
      affinity to normal human red blood cells.
AB  - Synthetic 20-mer long non-overlapped peptides, from STEVOR protein, were tested
      in RBC binding assays for identifying STEVOR protein regions having high RBC
      binding activity and evaluating whether these regions inhibit Plasmodium
      falciparum in vitro invasion. Affinity constants, binding site number per cell
      and Hill coefficients were determined by saturation assay with high activity
      binding peptides (HABPs). HABP binding assays using RBCs previously treated with
      enzymes were carried out to study the nature of the receptor. The molecular
      weight of RBC surface proteins interacting with HABPs was determined by cross
      linking assays and SDS-PAGE analysis. RBC binding assays revealed that peptides
      30561 (41MKSRRLAEIQLPKCPHYNND60), 30562 (61PELKKIIDKLNEERIKKYIE80) and 30567
      (161ASCCKVHDNYLDNLKKGCFG180) bound saturably and with high binding activity,
      presenting nanomolar affinity constants. HABP binding activity to RBCs previously
      treated with neuraminidase and trypsin decreased, suggesting that these peptides
      bound to RBC surface proteins and that such binding could be sialic acid
      dependent. Cross-linking and SDS-PAGE assays showed that the three HABPs
      specifically bound to 30 and 40 kDa molecular weight RBC membrane proteins.
      Peptides 30561, 30562 and 30567 inhibited P. falciparum in vitro invasion of red
      blood cells in a concentration-dependent way. Goat sera having STEVOR protein
      polymeric peptides antibodies inhibit parasite in vitro invasion depending on
      concentration. Three peptides localized in STEVOR N-terminal and central regions
      had high, saturable, binding activity to 30 and 40 kDa RBC membrane proteins.
      These peptides inhibited the parasite's in vitro invasion, suggesting that STEVOR
      protein regions are involved in P. falciparum invasion processes during intra
      erythrocyte stage.

PMID- 15949632
TI  - Synthesis and biological properties of chimeric interferon-alpha2b peptides.
AB  - We have previously reported the antiproliferative activity of synthetic sequences
      29-35 and 122-139 of the interferon-alpha2b (IFN-alpha2b), both probably
      representing a common receptor recognition domain. In the search of new peptidic
      agonists, we designed and synthesized the linear peptide (Gly)2-122-137-Gly138
      Gly29-30-35-(Gly)2, in which Gly residues replaced the 138 and 29 Cys bound
      through a disulfide bridge in the native cytokine. Additionally, a cyclic analog
      was obtained by reaction of the N- and C-terminal ends of the linear fragment.
      Thus, the distance that separates residues 122 and 35 in the crystalline
      structure of the IFN-alpha2b was maintained through a (Gly)4 bridge. When the
      influence of chimeric peptides on the proliferation of WISH cells was studied, it
      was shown that both derivatives significantly diminished cell growth. A more
      evident inhibitory effect on (125)I-IFN-alpha2b binding to WISH cell-membrane
      receptors was observed for both peptides. Results indicated that chimeric IFN
      alpha2b peptides behaved as partial agonists of the IFN-alpha2b molecule and may
      be of interest for drug design purposes.

PMID- 15949633
TI  - Alpha-melanocyte stimulating hormone cytoprotective biology in human dermal
      fibroblast cells.
AB  - Alpha-melanocyte stimulating hormone (alpha-MSH) has been identified as a potent
      anti-inflammatory peptide effective in various tissues including skin. It acts by
      inhibiting the production and action of several pro-inflammatory stimuli
      including TNF-alpha, IL-1beta and LPS in a number of cell types. The role of such
      stimuli in inducing cellular apoptosis is also well described; however the
      precise role of alpha-MSH in apoptosis is presently unclear, with studies
      reporting both anti- and pro-apoptotic activity. The present study demonstrates
      that cultured human dermal fibroblasts respond to serum depletion and TNF-alpha,
      IL-1beta and LPS with an increase in membrane permeability, a decrease in
      viability and an increase in phosphatidylserine externalization (indicative of
      apoptosis) over 48-96 h. alpha-MSH (at 10(-6) M, but not 10(-9) M) was found to
      inhibit the serum free and pro-inflammatory mediated reduction in membrane
      permeability and cellular viability and also inhibited increases in apoptosis. In
      conclusion, data support a cytoprotective and anti-apoptotic role of the alpha
      MSH peptide in human dermal fibroblast cells.

PMID- 15949634
TI  - Synthesis and biological studies of nociceptin derivatives containing the DTPA
      chelating group for further labeling with therapeutic radionuclides.
AB  - Nociceptin is an endogenous anti-opiate heptadecapeptide primarily interacting
      with the nociceptin (NOP) receptor. This neuropeptide-receptor system is involved
      in pain regulation, tolerance to and dependence on opiates as well as many other
      physiological and pathophysiological events. The role and mechanisms of
      nociceptin in pathological conditions is not clearly known yet. In an attempt to
      have a radiopharmaceutical labeled either with 99mTc or (111)In, we incorporated
      diethylenetriaminepentaacetic acid (DTPA) as chelator into the structure of
      [Arg14,Lys15]nociceptin(1-17)-NH2 at the epsilon-amino group of Lys15. Such a
      radiopeptide may be useful in imaging for diagnostical purposes. Preparation of
      the peptide ligands was carried out by solid phase synthesis. Two peptides
      containing DTPA were obtained and purified. The products were
      [Arg14,Lys(DTPA)15]nociceptin(1-17)-NH2 and its cross-linked dimer on the basis
      of mass spectrometric analysis. In (115)In3+ binding experiments the conjugates
      exhibited preserved indium ion chelating properties, indicating the potential use
      of radiolabeled DTPA-nociceptin derivatives as radiopharmaceutical. Biological
      properties of these compounds were studied in rat brain membrane preparations by
      radioligand binding, functional biochemical [35S]GTPgammaS binding assays and
      mouse vas deferens (MVD) bioassay. Besides the similar in vitro binding
      characteristics to nociceptin receptor, both of the DTPA-chelated compounds were
      more potent and efficient than nociceptin in functional biochemical and mouse vas
      deferens bioassays. Our further aim is to radiolabel these compounds in order to
      get a radiopharmaceutical which can be used diagnostically.

PMID- 15949635
TI  - NPY-induced feeding: pharmacological characterization using selective opioid
      antagonists and antisense probes in rats.
AB  - The ability of neuropeptide Y to potently stimulate food intake is dependent in
      part upon the functioning of mu and kappa opioid receptors. The combined use of
      selective opioid antagonists directed against mu, delta or kappa receptors and
      antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and
      KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the
      precise receptor subpopulations mediating feeding elicited by opioid peptides and
      agonists as well as homeostatic challenges. The present study examined the dose
      dependent (5-80 nmol) cerebroventricular actions of general and selective mu,
      delta, and kappa1 opioid receptor antagonists together with antisense probes
      directed against each of the four exons of the MOR-1 opioid receptor gene and
      each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor
      genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY
      induced feeding was dose-dependently decreased and sometimes eliminated following
      pretreatment with general, mu, delta, and kappa1 opioid receptor antagonists.
      Moreover, NPY-induced feeding was significantly and markedly reduced by antisense
      probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the
      DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1
      gene. Thus, whereas the opioid peptides, beta-endorphin and dynorphin A(1-17)
      elicit feeding responses that are respectively more dependent upon mu and kappa
      opioid receptors and their genes, the opioid mediation of NPY-induced feeding
      appears to involve all three major opioid receptor subtypes in a manner similar
      to that observed for feeding responses following glucoprivation or lipoprivation.

PMID- 15949636
TI  - Perigestational suppression of weight gain with central leptin gene therapy
      results in lower weight F1 generation.
AB  - The efficacy of central leptin therapy on weight homeostasis through various
      phases of reproduction, pregnancy outcome and postnatal, prepubertal and pubertal
      growth of offspring was assessed. Enhanced leptin transgene expression after a
      single intracerebroventricular injection of recombinant adeno-associated virus
      vector encoding the leptin gene (rAAV-lep) decreased calorie intake and weight in
      adult nulliparous female rats. rAAV-lep treated rats conceived normally,
      displayed unremarkable pregnancy rate, parturition and delivered normal sized
      litters. Significantly lower weight was maintained through gestation, lactation,
      and post-lactation periods. The maintenance of a modest weight reduction was
      accompanied by voluntarily reduced calorie intake, increased thermogenic energy
      expenditure, decreased adiposity as reflected by drastically reduced leptin
      levels, and suppressed insulin and insulin-like growth factor 1 levels through
      lactation and post-lactation in rAAV-lep treated dams. The offspring at birth
      weighed significantly less than those of controls and this lower weight range was
      sustained during postnatal, prepubertal, pubertal and adult (3 months old)
      periods, contemporaneous with metabolic circulating hormones in the normal range.
      For the first time we show the persistent efficacy of central leptin gene therapy
      to suppress weight gain through all phases of reproduction, lactation and post
      lactation in dams and reveal the potential imprinting link to producing lower
      weight in the F1 generation.

PMID- 15949638
TI  - Urocortin 3/stresscopin in human colon: possible modulators of gastrointestinal
      function during stressful conditions.
AB  - Urocortin 3 (Ucn 3) or stresscopin (SCP) is a new member of the corticotropin
      releasing factor (CRF) neuropeptide family and is a specific ligand for CRF type
      2 receptor (CRF2). CRF receptors are known to be expressed in the
      gastrointestinal tract and are considered to play pathophysiological roles, for
      example, in gastrointestinal motility under stress. We, therefore, examined Ucn 3
      expression in the normal human large intestine obtained from surgery and autopsy
      in order to clarify this local response to stress in human intestine. Both
      immunohistochemistry and mRNA in situ hybridization demonstrated Ucn 3 expression
      in myenteric and submucosal nervous plexus, in vascular endothelial cells (VECs)
      and vascular smooth muscle cells (VSMCs) of blood vessels in subserosa, in smooth
      muscle layers of the large intestine, and in enterochromaffin cells. In contrast
      to Urocortin 1 (Ucn 1), Ucn 3 was hardly detected in lamina propria (LP)
      inflammatory cells in colonic mucosa. In addition, immunohistochemistry
      demonstrated CRF2 expression in myenteric and submucosal nervous plexus, in
      smooth muscle layers, in VECs, in VSMCs and in lamina propria inflammatory cells.
      Immunoreactive Ucn 3 was also detected in the large intestine by RIA, with high
      concentrations detected in the rectum (15.4+/-9.5 pmol/g wet weight, mean+/-SEM,
      n=3) and sigmoid colon (6.5+/-3.5 pmol/g wet weight, n=5). Reverse-phase HPLC of
      the human large intestine disclosed peaks eluting in the position of synthetic
      Ucn 3 or SCP. These findings all suggest that Ucn 3 plays some physiological or
      pathological roles in the modulation of gastrointestinal functions during
      stressful conditions in different manners from Ucn 1.

PMID- 15949637
TI  - Peripheral injection of sauvagine prevents repeated colorectal distension-induced
      visceral pain in female rats.
AB  - We investigated the effects of peripheral injection of sauvagine, a CRF2>CRF1
      receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets
      of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced
      visceromotor response (VMR) measured as area under the curve (AUC) of abdominal
      muscle contraction in conscious female rats. Sauvagine (10 or 20 microg/kg, s.c.)
      abolished the 226.7+/-64.3% and 90.4+/-38.1% increase in AUC to the 2nd CRD
      compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague
      Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist,
      antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced
      response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further
      the AUC by 33.5+/-23.3% and 63.5+/-7.2%, respectively in Fisher rats. These data
      suggest that peripheral CRF2 receptor activation exerts antinociceptive effects
      on CRD-induced visceral pain, whereas CRF1 contributes to visceral sensitization.

PMID- 15949639
TI  - Importance of N- and C-terminal regions of gastrin-Gly for preferential binding
      to high and low affinity gastrin-Gly receptors.
AB  - G17-Gly has been shown to stimulate the growth of DLD-1 human colon cancer cells
      in a biphasic manner via high and low affinity receptors. In the current study,
      the existence of heterogeneous receptor populations for G17-Gly on the HT-29
      human colon cancer cell line was investigated. The effect of either N- or C
      terminal peptide truncation on receptor binding and cell growth stimulation was
      also explored. [Leu15]G17-Gly bound to both high (nM) and low (microM) affinity
      sites on HT-29 cells. The peptide stimulated cell growth in a dose-dependent and
      biphasic manner with maximal stimulation at 10(-9) M peptide concentration,
      suggesting that, as in the case of DLD-1 cells, it is the high affinity receptor
      which is responsible for the growth-promoting effects. In contrast, G17(1-12)
      stimulated the growth of HT-29 cells in a sigmoidal fashion with an EC50 of
      4.6x10(-9) M. Sequential N-terminal truncation of [Leu15]G17-Gly results in
      decreased binding to the high affinity G17-Gly receptor on DLD-1 cells.
      [Leu15]G17(11-17)Gly bound to the low affinity G17-Gly receptor with an affinity
      similar to that of the full sequence peptide but was unable to displace the
      radioligand from high affinity sites. G17(1-6)-NH2 was unable to displace [3H]G17
      Gly from either site. These results suggest that the important residues for
      binding to the low affinity receptor are in the C-terminal region of the peptide
      while those required for interaction with the high affinity receptor lie further
      towards the N-terminus.

PMID- 15949640
TI  - Endothelin-3 applied to the brain evokes opposite effects on bile secretion
      mediated by a central nitric oxide pathway.
AB  - We sought to establish Endothelin (ET-3) role in the central regulation of bile
      secretion in the rat. The intracerebroventricular (icv) injection of ET-3 evoked
      a cholestatic or a choleretic effect depending on the administered dose. Lower
      doses increased bile flow and bicarbonate excretion, whereas higher doses
      decreased bile flow and bile acid output. ET-3 effects were dependent on brain
      nitric oxide and independent of the autonomic nervous system or hemodynamic
      variations. A selective ETB antagonist abolished the cholestatic effect, whereas
      the choleretic effect was totally inhibited by either ETA or ETB selective
      blockade. These results show that ET-3 applied to the brain modified through a
      nitric oxide pathway distinct bile flow fractions depending on the administered
      dose and give further insights into the complexity of brain-liver interaction.

PMID- 15949641
TI  - The impact of chronic nandrolone decanoate administration on the NK1 receptor
      density in rat brain as determined by autoradiography.
AB  - Adult male Sprague-Dawley rats were treated with the anabolic androgenic steroid
      nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum)
      during 14 days. The effect on the densities of the neurokinin NK1 receptor in
      brain was examined with autoradiography. An overall tendency of attenuation of
      NK1 receptor density was observed after completed treatment with nandrolone
      decanoate. The density of the NK1 receptor was found to be significantly lower
      compared to control animals in the nucleus accumbens core (37% density
      reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in
      ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus
      (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region,
      no structures exhibited any significant reduction of NK1 receptor density. This
      result provides additional support to the hypothesis that substance P and the NK1
      receptor may be involved as important components that participate in mediating
      physiological responses including the adverse behaviors often associated with
      chronically administrated anabolic androgenic steroids in human.

PMID- 15949642
TI  - Potentiation of bradykinin actions by analogues of the bradykinin potentiating
      nonapeptide BPP9alpha.
AB  - Synthetic analogues of the bradykinin potentiating nonapeptide BPP9alpha indicate
      significantly different structural requirements for potentiation of the
      bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of
      isolated somatic angiotensin I-converting enzyme (ACE). The results disprove the
      ACE inhibition as the only single mechanism and also the direct interaction of
      potentiating peptides with the bradykinin receptors in transfected COS-7 cells as
      molecular mechanism of potentiation. Our results indicate a stimulation of
      inositol phosphates (IPn) formation independently from the B2 receptor.
      Furthermore, the results with La3+ support the role of extracellular Ca2+ and its
      influx through corresponding channels. The missing effect of calyculin on the GPI
      disproves the role of phosphatases in the potentiating action. These experimental
      studies should not only contribute to a better understanding of the potentiating
      mechanisms but also incorporate a shift in the research towards the immune
      system, in particular towards the immunocompetent polymorphonuclear leukocytes.
      The chemotaxis of these cells can be potentiated most likely by exclusive
      inhibition of the enzymatic degradation of bradykinin. Thus the obtained results
      give evidence that the potentiation of the bradykinin action can occur by
      different mechanisms, depending on the system and on the applied potentiating
      factor.

PMID- 15949644
TI  - Adrenomedullin induces heme oxygenase-1 gene expression and cGMP formation in rat
      vascular smooth muscle cells.
AB  - Adrenomedullin (ADM) is a potent vasodilatory peptide. It regulates blood
      pressure by increasing cyclic adenosine monophosphate (cAMP) and guanosine-3',5'
      monophosphate (cGMP). We sought to investigate the effect of ADM on heme
      oxygenase-1 (HO-1) gene expression and cGMP formation in cultured rat vascular
      smooth muscle cells (VSMCs). ADM treatment, 10(-9) and 10(-8) mol/L, increased
      cGMP production, and it increased the intracellular cGMP content of platelets
      coincubated with VSMCs. It increased cGMP content by 158.8% and 273.5%,
      respectively; increased HO-1 activity by 49.5% and 87%, respectively; augmented
      HO-1 protein levels by 66% and 126%, respectively; upregulated the steady-state
      level of HO-1 mRNA by 73% and 159%, respectively, and increased HO-1 mRNA
      transcription synthesis by four- and seven-fold, respectively. These results
      suggest that ADM induces HO-1 gene expression and cGMP formation in rat VSMCs.

PMID- 15949643
TI  - Cardiac actions of central but not peripheral urotensin II are prevented by beta
      adrenoceptor blockade.
AB  - Urotensin II (UII) is a highly conserved peptide that has potent cardiovascular
      actions following central and systemic administration. To determine whether the
      cardiovascular actions of UII are mediated via beta-adrenoceptors, we examined
      the effect of intravenous (IV) propranolol on the responses to
      intracerebroventricular (ICV) and IV administration of UII in conscious sheep.
      Sheep were surgically instrumented with ICV guide tubes and flow probes or
      cardiac sympathetic nerve recording electrodes. ICV UII (0.2 nmol/kg over 1 h)
      caused prolonged increases in heart rate (HR; 33 +/- 11 beats/min; P < 0.01),
      dF/dt (581 +/- 83 L/min/s; P < 0.001) and cardiac output (2.3 +/- 0.4 L/min; P <
      0.001), accompanied by increases in coronary (19.8 +/- 5.4 mL/min; P < 0.01),
      mesenteric (211 +/- 50 mL/min; P < 0.05) and iliac (162 +/- 31 mL/min; P < 0.001)
      blood flows and plasma glucose (7.0 +/- 2.6 mmol/L; P < 0.05). Propranolol (30 mg
      bolus followed by 0.5 mg/kg/h IV) prevented the cardiac responses to ICV UII and
      inhibited the mesenteric vasodilatation. At 2 h after ICV UII, when HR and mean
      arterial pressure (MAP) were increased, cardiac sympathetic nerve activity (CSNA)
      was unchanged and the relation between CSNA and diastolic pressure was shifted to
      the right (P < 0.05). The hyperglycemia following ICV UII was abolished by
      ganglion blockade but not propranolol. IV UII (20 nmol/kg) caused a transient
      increase in HR and fall in stroke volume; these effects were not blocked by
      propranolol. These results demonstrate that the cardiac actions of central UII
      depend on beta-adrenoreceptor stimulation, secondary to increased CSNA and
      epinephrine release, whereas the cardiac actions of systemic UII are not mediated
      by beta-adrenoreceptors and probably depend on a direct action of UII on the
      heart.

PMID- 15949645
TI  - Efficient isolation of peptide ligands for the endothelial cell protein C
      receptor (EPCR) using candidate receptor phage display biopanning.
AB  - Phage display biopanning has been used for a number of applications including
      ligand generation for targeted drug delivery, targeting gene therapy vectors and
      identification of protein-protein interaction sites. In this study, a random
      phage display library was used to isolate peptide ligands to the endothelial
      protein C receptor (EPCR), identifying 74 different peptide sequences and several
      motifs. Binding to EPCR was characterized by a solid phase binding assay,
      demonstrating that 95% of isolated peptides were specific for EPCR. Several
      homologies with potential relevance to EPCR biology were identified, the most
      notable being leukolysin (MT-MMP6) and cerastocytin.

PMID- 15949646
TI  - Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in
      rodents.
AB  - Biochemical analysis revealed that angiotensin-converting enzyme related carboxy
      peptidase (ACE2) cleaves angiotensin (Ang) II to Ang-(1-7), a heptapeptide
      identified as an endogenous ligand for the G protein-coupled receptor Mas. No
      data are currently available that systematically describe ACE2 distribution and
      activity in rodents. Therefore, we analyzed the ACE2 expression in different
      tissues of mice and rats on mRNA (RNase protection assay) and protein levels
      (immunohistochemistry, ACE2 activity, western blot). Although ACE2 mRNA in both
      investigated species showed the highest expression in the ileum, the mouse organ
      exceeded rat ACE2, as also demonstrated in the kidney and colon. Corresponding to
      mRNA, ACE2 activity was highest in the ileum and mouse kidney but weak in the rat
      kidney, which was also confirmed by immunohistochemistry. Contrary to mRNA, we
      found weak activity in the lung of both species. Our data demonstrate a tissue-
      and species-specific pattern for ACE2 under physiological conditions.

PMID- 15949647
TI  - Human sorbin is generated via splicing of an alternative transcript from the
      ArgBP2 gene locus.
AB  - We demonstrate that the human sorbin polypeptide is generated via splicing of an
      alternative transcript from the ArgBP2 gene locus. Previous studies have
      demonstrated that the central 139 amino acid region of the porcine sorbin
      polypeptide exhibits 95% homology to part of the human ArgBP2 protein. Yet
      neither the sorbin N- nor C-terminus has been identified in ArgBP2 or any other
      protein to date. Using computational analysis, we locate the sorbin N- and C
      termini in the human ArgBP2 gene locus, and demonstrate that they are spliced to
      the 5' and 3' ends of the 95% homologous region. In addition, several sequence
      anomalies were identified in the putative human sorbin cDNA (AF396457). Thus, a
      revised human sorbin nucleotide sequence is proposed.

PMID- 15949648
TI  - A meta-analysis of worldwide studies demonstrates an association between
      schizophrenia and tobacco smoking behaviors.
AB  - A meta-analysis of worldwide studies, found by a 10-year literature follow-up
      and/or by searching PubMed, was performed. Forty-two studies across 20 nations
      consistently demonstrated an association between schizophrenia and current
      smoking (weighted average odds ratio, OR=5.9; 95% confidence interval, CI 4.9-
      5.7). In 32 male studies across 18 nations, the weighted average OR was 7.2 (CI,
      6.1--8.3). In 25 female studies across 15 nations, the weighted average OR was
      3.3 (CI, 3.0--3.6). The association between schizophrenia and current smoking
      remained after using severe mentally ill controls (18 studies across 9 countries,
      weighted average OR was 1.9, CI 1.7--2.1) and controlling for other variables (3
      studies, adjusted ORs ranged 2-3). Heavy smoking (6 studies across 4 countries,
      ORs ranged 1.9--6.4) and high nicotine dependence were more frequent in smokers
      with schizophrenia versus the general population. There was no consistent
      evidence that heavy smoking or high nicotine dependence was more frequent in
      smokers with schizophrenia versus severe mentally ill controls. Cessation rates
      were lower in schizophrenia smokers versus the general population. Schizophrenia
      patients had a higher prevalence of ever smoking than the general population (9
      studies across 6 countries, weighted average OR=3.1, CI 2.4--3.8) and than severe
      mentally ill patients (5 studies across 5 countries, OR=2.0, CI 1.6--2.4).
      Moreover, in two studies adjusting for confounders schizophrenia patients had an
      increased risk of starting daily smoking than controls. Thus, people who are
      going to develop schizophrenia have risk factors that make them more vulnerable
      to start smoking.

PMID- 15949650
TI  - N-acetylaspartate reductions in the mediodorsal and anterior thalamus in men with
      schizophrenia verified by tissue volume corrected proton MRSI.
AB  - OBJECTIVE: Deficits in the mediodorsal and anterior nuclei of the thalamus may
      contribute to the psychopathological symptoms of schizophrenia. These thalamic
      nuclei have been found to be abnormal in schizophrenia and have close connections
      with other brain structures implicated in the disorder. We therefore examined
      schizophrenia-related alterations in brain metabolite levels specifically in the
      mediodorsal and anterior thalamic subregions. METHOD: We used in vivo proton
      magnetic resonance spectroscopic imaging ((1)H MRSI) to measure N-acetylaspartate
      (NAA), choline-containing compounds (Cho), and creatine+phosphocreatine (Cr) in
      the mediodorsal and anterior thalamus in 22 male patients with schizophrenia and
      22 male controls. Magnetic resonance imaging (MRI) tissue segmentation and
      thalamic volume mask techniques were performed to distinguish the thalamus,
      extrathalamic gray and white matter, and CSF within the spectroscopic voxels.
      RESULTS: Compared to healthy subjects, patients with schizophrenia had
      significantly lower NAA in the mediodorsal and anterior thalamus bilaterally. No
      significant differences in Cho or Cr levels were seen. NAA was significantly
      higher in the left thalamus relative to the right in both groups. We found a
      strong negative correlation between left thalamic NAA and duration of illness,
      even after partialling out the effect of age. Tissue segmentation and thalamic
      volume mask techniques detected no group or lateralized differences in tissue
      type or CSF percentages, demonstrating that the metabolite reductions were not an
      artifact of spectroscopic voxel heterogeneity. CONCLUSIONS: These findings
      suggest diminished function and/or structure in the mediodorsal and anterior
      thalamus in male patients with schizophrenia and support earlier research
      demonstrating schizophrenia-related abnormalities in the thalamus and its
      circuitry.

PMID- 15949649
TI  - Unchanged packing density but altered size of neurofilament immunoreactive
      neurons in the prefrontal cortex in schizophrenia and major depression.
AB  - Morphometric changes in the general population of Nissl-stained neurons in area 9
      of the dorsolateral prefrontal cortex have been reported in major depressive
      disorder (MDD) and schizophrenia. These alterations include lamina-specific
      reductions in the packing density of neuronal somata in MDD, increases or
      reductions in the density of neuronal somata in schizophrenia, and reductions in
      average size of neuronal somata in both MDD and schizophrenia. These changes are
      prominent in deep layer III, where pyramidal excitatory neurons establishing
      cortico-cortical association connections are localized. To test whether deep
      layer III pyramidal neurons are differentially affected in MDD or schizophrenia,
      an antibody was used that labels both phosphorylated and non-phosphorylated forms
      of the 200 kD neurofilament protein (NF200) in pyramidal cells of layer III in
      area 9. The packing density and somal size of NF200-immunoreactive (IR) pyramidal
      neurons were measured in area 9 in 13 subjects with nonpsychotic MDD, 11 subjects
      with schizophrenia and 13 psychiatrically normal controls. Analysis of covariance
      did not reveal a difference in packing density among groups. However, the mean
      size of NF200-IR somata was significantly larger in subjects with schizophrenia
      than in controls. These results indicate that this neuronal subpopulation does
      not contribute to the smaller average size of neuronal somata in layer III of
      prefrontal cortical area 9 in schizophrenia or MDD. In addition, the enlarged
      somal size in schizophrenia as compared to controls suggests that NF200 neurons
      may contribute differentially to unique cognitive disturbances present in
      schizophrenia and not in MDD subjects.

PMID- 15949651
TI  - No association of the brain-derived neurotrophic factor (BDNF) gene C-270T
      polymorphism with schizophrenia.
AB  - Brain-derived neurotrophic factor (BDNF) regulates a variety of neuromodulatory
      processes during development, as well as in adulthood. It has been proposed as a
      risk factor for schizophrenia. We have investigated a possible association
      between schizophrenia and the C-270T polymorphism in the brain-derived
      neurotrophic factor (BDNF) gene in 397 schizophrenic patients and 380 control
      subjects. The diagnosis of schizophrenia was made for each patient by at least
      two psychiatrists, using DSM-IV and ICD-10 criteria in structured clinical
      interviews for DSM-IV Axis I disorders (SCID). No association was found between
      schizophrenia and the analyzed polymorphism, for either genotype or allele
      distribution (for genotype: p=0.513, for alleles: p=0.812). Differences were not
      statistically significant when analyzed separately by sex. For males, the
      differences for genotype distribution and allele frequency were p=0.078 and
      p=0.162 respectively and for females: p=0.441 and p=0.315. Thus, our data
      indicate that variations in the BDNF gene are unlikely to be an important factor
      in susceptibility to schizophrenia.

PMID- 15949652
TI  - The association of the HLA in patients with schizophrenia, schizoaffective
      disorder, and in their biological relatives.
AB  - To determine the association of the HLA in 50 patients with schizophrenia,
      schizoaffective disorder, 48 healthy controls, 41 biological relatives without
      psychiatric disease, and 48 biological relatives with mood disorder, the HLA
      genotype at the class I and class II were determined. The subjects were
      interviewed by structured diagnostic criteria categorized according to DSM-IV,
      axis I, (SCID-IV). Significant positive association was found with HLA-B.15 in
      patients, family with humor disorder and without mental disorder (p=0.003) and
      negative association of the HLA-B.35 in relatives without psychiatric disease
      (p=0.03). The HLA-B.15 frequency was significantly increased in a subgroup of
      patients with age at onset in the early 20s, lower educational achievement,
      occupational disability, chronically ill, more paranoid type. These findings
      suggest the existence of some involvement of an immunogenetic mechanism in a
      subgroup of schizophrenic, schizoaffective patients, and biological relatives.

PMID- 15949653
TI  - Prefrontal functioning during context processing in schizophrenia and major
      depression: an event-related fMRI study.
AB  - Patients with schizophrenia frequently demonstrate hypofrontality in tasks that
      require executive processing; however questions still remain as to whether
      prefrontal cortex dysfunctions are specific to schizophrenia, or a general
      feature of major psychopathology. Context processing is conceptualized as an
      executive function associated with attention and working memory processes.
      Impairment in the ability of patients with schizophrenia to represent and
      maintain context information has been previously reported in a number of studies.
      To examine the question of the specificity of a context processing deficit to
      schizophrenia, we used functional MRI and an expectancy AX continuous performance
      task designed to assess context processing in a group of healthy controls (n=9),
      depressed patient controls (n=10), and patients with schizophrenia (n=7). The
      behavioral performance was consistent with a context processing deficit in
      patients with schizophrenia, but not those with depression. The imaging data
      replicate previous results in showing abnormal activity in the right middle
      frontal gyrus (BA9) in schizophrenia patients related to context processing.

PMID- 15949654
TI  - Cortical intercorrelations of temporal area volumes in schizophrenia.
AB  - BACKGROUND: Abnormal temporal connections with other cortical areas may underlie
      some of the most prominent cognitive deficits described in schizophrenia. In
      order to evaluate the relationship between temporal and other cortical regions in
      schizophrenia, we examined the intercorrelations of volumetric measures of gray
      and white matter for each Brodmann's area of the temporal lobe with volumes in
      the rest of the cortex in patients with schizophrenia and normal comparison
      subjects. METHODS: MR images were acquired in normal subjects (n=46) and patients
      with schizophrenia (n=106), divided into good-outcome (n=52) and poor-outcome
      (Kraepelinian; n=54) subtypes; and correlational patterns between the volumes of
      individual Brodmann's areas were compared and examined in relation to outcome.
      RESULTS: Positive frontotemporal intercorrelations were significantly stronger
      while negative frontotemporal intercorrelations were weaker in schizophrenia
      patients as compared to normal subjects. Correlations between the right temporal
      pole and other temporal regions were significantly weaker in schizophrenia
      patients than in controls. When compared to normal controls and good-outcome
      patients, schizophrenia patients with poor outcomes showed a selective pattern of
      stronger gray matter correlations between the medial temporal vs. primary visual
      and between primary auditory vs. dorsolateral prefrontal cortices, all in the
      left hemisphere. CONCLUSIONS: Strengthening of positive associations among the
      temporal and extratemporal (mainly frontal and occipital) regions as well as
      weakening of regional intercorrelations within the temporal lobe in patients
      appear to constitute the major differences of correlational patterns in
      schizophrenia patients and normal subjects. Present findings may be implicated in
      object recognition deficits seen in patients with schizophrenia, as well as in
      purportedly deficient spatial and semantic processing of both auditory and visual
      information that may be associated with poor outcome.

PMID- 15949655
TI  - Investigation of the apolipoprotein-L (APOL) gene family and schizophrenia using
      a novel DNA pooling strategy for public database SNPs.
AB  - We performed an extensive genetic association study of the six known
      apolipoprotein-L (APOL) genes and schizophrenia (SZ) using a novel DNA pooling
      strategy. The APOL genes are both positional and functional candidate genes for
      SZ. This gene family maps to chromosome 22q12.3, a region implicated by SZ
      linkage studies as likely to contain one or more SZ susceptibility genes. A
      recent gene expression study demonstrated up-regulation of APOL1, 2, and 4 in
      post-mortem brain samples from SZ patients compared to controls in two
      independent samples. To test for genetic association with SZ, we analyzed 143
      SNPs from dbSNP from across the APOL genes in an Irish sample of 219 cases and
      231 controls. Of these 143 SNPs, 51 (36%) were polymorphic in our Irish sample
      and were genotyped using a novel three-stage DNA pooling strategy. This strategy
      does not require the identification of a heterozygous individual for DNA pooling
      association analysis and is therefore very efficient when using public database
      SNPs. We found no evidence to support the hypothesis that genetic variation at
      the APOL genes contributes to SZ susceptibility in our sample.

PMID- 15949656
TI  - Extralimital triradii as a putative marker of schizotypy.
AB  - Dermatoglyphic anomalies are reported to occur at a higher rate in schizophrenic
      patients and schizotypic individuals than in the general population, supporting
      the hypothesis that they are a marker of vulnerability for such conditions.
      Dermatoglyphic anomalies are hypothesized to indicate severe disruptions in the
      second trimester of prenatal development, a time period that appears to be
      etiologically relevant to the development of schizophrenia and related
      conditions. The present study provides the first examination of extralimital
      triradii in schizotypic young adults (n=197) and control participants (n=135)
      identified by the Revised Social Anhedonia Scale [Eckblad, M., Chapman, L.J.,
      Chapman, J.P., Mishlove, M., 1982. The Revised Social Anhedonia Scale.
      Unpublished test (copies available from T.R. Kwapil, Department of Psychology,
      University of North Carolina at Greensboro P.O. Box 26164 Greensboro, NC 27402
      6164)], the Perceptual Aberration Scale [Chapman, L.J., Chapman, J.P., Raulin,
      M.L., 1978. Body image aberration in schizophrenia. J. Abnorm. Psychol. 87, 399-
      407], the Magical Ideation Scale [Eckblad, M.L., Chapman, L.J., 1983. Magical
      ideation as an indicator of schizotypy. J. Consult. Clin. Psychol. 51, 215--225],
      and the Physical Anhedonia Scale [Chapman, L.J., Chapman, J.P., Raulin, M.L.,
      1976. Scales for physical and social anhedonia. J. Abnorm. Psychol. 85, 374-
      382]. As hypothesized, the schizotypic participants (6.6%) exhibited
      significantly higher rates of extralimital triradii than control participants
      (1.5%). These findings strongly encourage the future investigation of
      extralimital triradii in at-risk and psychotic populations.

PMID- 15949657
TI  - Manual for the Extrapyramidal Symptom Rating Scale (ESRS).
AB  - The Extrapyramidal Symptom Rating Scale (ESRS) was developed to assess four types
      of drug-induced movement disorders (DIMD): Parkinsonism, akathisia, dystonia, and
      tardive dyskinesia (TD). Comprehensive ESRS definitions and basic instructions
      are given. Factor analysis provided six ESRS factors: 1) hypokinetic
      Parkinsonism; 2) orofacial dyskinesia; 3) trunk/limb dyskinesia; 4) akathisia; 5)
      tremor; and 6) tardive dystonia. Two pivotal studies found high inter-rater
      reliability correlations in both antipsychotic-induced movement disorders and
      idiopathic Parkinson disease. For inter-rater reliability and certification of
      raters, >or=80% of item ratings of the complete scale should be +/-1 point of
      expert ratings and >or=70% of ratings on individual items of each ESRS subscale
      should be +/-1 point of expert ratings. During a cross-scale comparison, AIMS and
      ESRS were found to have a 96% (359/374) agreement between TD-defined cases by DSM
      IV TD criteria. Two recent international studies using the ESRS included over
      3000 patients worldwide and showed an incidence of TD ranging from 10.2% (2000)
      to 12% (1998). ESRS specificity was investigated through two different
      approaches, path analyses and ANCOVA PANSS factors changes, which found that ESRS
      measurement of drug-induced EPS is valid and discriminative from psychiatric
      symptoms.

PMID- 15949658
TI  - The crossover approach to switching antipsychotics: what is the evidence?
AB  - Clinicians frequently use a crossover approach in switching antipsychotics,
      although historically there has been a lack of data addressing the question of
      switch strategies. To establish if there is now empiric evidence that may guide
      clinicians in this regard, a MEDLINE search to April 2004 was carried out to
      identify published, randomized and controlled trials that have addressed this
      topic. A total of 404 articles were identified in the search, which resulted in
      the identification of four reports meeting the criteria. The four studies
      evaluated switching strategies to one of three atypical antipsychotics:
      aripiprazole, olanzapine (two reports), and ziprasidone. The switching process
      itself could be subdivided as follows: discontinuation (abrupt vs. gradual); and,
      replacement (abrupt vs. gradual). Meta-analyses confirmed a lack of difference in
      outcome, regardless of approach. While a crossover approach does not appear to
      increase adverse events, the available empiric evidence does not support its
      clinical superiority on various outcome measures. The existing data therefore
      argue against the position that a crossover approach in switching antipsychotics
      represents a 'safer' means of preventing clinical deterioration during the
      switch.

PMID- 15949659
TI  - Histories of childhood maltreatment in schizophrenia: relationships with
      premorbid functioning, symptomatology, and cognitive deficits.
AB  - A number of studies have demonstrated an increased rate of histories of childhood
      maltreatment among adults with serious mental illness. The present investigation
      documented the presence of childhood maltreatment in a sample of 40 psychiatric
      inpatients with schizophrenia spectrum disorders. The type (neglect, physical
      abuse, sexual abuse), duration, and severity of childhood maltreatment was
      examined along with measures of premorbid functioning, current symptomatology,
      and cognitive functioning. Participants with histories of maltreatment were
      significantly more likely to have poorer peer relationships in childhood, more
      difficulty in school, an earlier age at first hospitalization, more previous
      hospitalizations, elevated symptoms of anxiety, depression, and suicidality on
      the Brief Psychiatric Rating Scale (BPRS), and more impaired performance on a
      task of visual-perceptual organization. Severity and frequency of childhood
      maltreatment were both positively correlated with hallucinations and delusions on
      the BPRS. Linear trend analysis indicated a pattern of more severe impairment as
      the number of types of maltreatment increased. No relationships were found
      between maltreatment and measures of executive functioning, verbal fluency, or
      verbal processing speed. A history of childhood maltreatment appears to be a
      significant determinant of premorbid functioning, illness-related symptom
      expression, and specific forms of cognitive dysfunction.

PMID- 15949660
TI  - The association between social anxiety and social functioning in first episode
      psychosis.
AB  - The purpose of the study was to examine the relationship between social anxiety
      and social functioning in first episode psychosis, and to determine whether those
      with psychosis have any maladaptive or irrational beliefs regarding social
      situations. A sample of 60 first episode patients (41 males, 19 females)
      participated in the study. The presence of social phobia was determined using the
      Structured Clinical Interview for DSM-IV (SCID-I). Measures included The Social
      Phobia and Anxiety Inventory (SPAI), the Social Functioning Scale (SFS), the
      Quality of Life Scale (QLS) and the Social Interaction Self-Statement Test.
      Thirty-two percent of the sample met SCID-I criteria for social phobia and
      approximately 60% of participants were experiencing elevated levels of social
      anxiety according to the SPAI (M=69.57, S.D.=27.42). Results were that negative
      symptoms and negative self-statements, but not social anxiety, were significant
      predictors of social functioning. This has implications for addressing these
      negative cognitions in early psychosis.

PMID- 15949661
TI  - Attentional and neurocognitive characteristics of high-risk offspring of parents
      with schizophrenia compared with DSM-IV attention deficit hyperactivity disorder
      children.
AB  - Offspring of individuals with schizophrenia are at increased baseline risk for a
      range of early mental disorders. Studies investigating the premorbid
      characteristics of individuals with schizophrenia indicate that they suffer from
      social, behavioral, attentional and neurocognitive impairments, often resembling
      attention deficit hyperactivity disorder (ADHD). In this study, we compared the
      executive functioning and general intelligence among three groups: (i) children
      and adolescents with DSM-IV ADHD (n=41), (ii) "high-risk" (HR) offspring of
      parents with DSM-IV schizophrenia, and (iii) normal comparison subjects (n=35).
      Our results indicated that both HR and ADHD groups had lower Verbal IQ scores.
      ADHD cases had significantly lower percent correct and total errors in Wisconsin
      Cart Sorting Test when compared with normal comparison subjects. The HR cases
      also had lower Performance IQ scores as well as worse abstraction--flexibility
      and comprehension performance. The HR group was further stratified with (HR-A)
      and without (HR-NA) comorbid ADHD, and HR-A subjects were significantly noted to
      be more impaired on most tests. The overall worse performance of HR offspring was
      attributable to significantly lower performance among the HR-A youth. Further,
      our results suggested that the most profoundly impaired HR subjects were in fact
      children and adolescents who also met criteria for ADHD. Future studies with
      broader neuropsychological test batteries are necessary to investigate the
      differences and similarities between ADHD and the HR-A subgroup.

PMID- 15949662
TI  - Clinical relevance of chronic catatonic schizophrenia in children and
      adolescents: evidence from a prospective naturalistic study.
AB  - The paper examines the phenomenology, diagnosis, and course of catatonia in
      children and adolescents. From 1993 to 2003, 21 boys and 9 girls, aged 12 to 18
      years, were admitted for a catatonic syndrome (0.6% of the total inpatient
      population). Phenomenology and associated diagnoses were similar to those
      reported in the adult literature but relative frequency differed, with
      schizophrenia being the most frequent diagnosis. Comparison of patients with
      schizophrenia (n=17) to those with other diagnoses (n=13) showed that the two
      groups differed in terms of sex ratio, type of onset and phenomenology of
      catatonic symptoms, duration of hospitalization, and severity at discharge. Using
      discriminant function analysis, the combination of three clinical variables--male
      gender, duration of catatonic episode, and severity at discharge--correctly
      classified 100% of cases in the schizophrenia group. Catatonia is an infrequent
      but severe condition in young people, and is usually associated with
      schizophrenia. There is a need for research in the field of catatonic
      schizophrenia in adolescents as it appears to be a clinically relevant but
      understudied subgroup.

PMID- 15949663
TI  - Obsessive compulsive symptoms in schizophrenia: frequency and clinical features.
AB  - OBJECTIVE: Prior studies have evaluated the occurrence and clinical effects of
      obsessive-compulsive (OC) symptoms in schizophrenia with varied results. This
      study systematically assessed the frequency and clinical impact of OC symptoms
      among outpatients with schizophrenia and schizoaffective disorder. METHOD: One
      hundred subjects with schizophrenia or schizoaffective disorder were evaluated
      with a 20-question detailed screen for the presence of OC symptoms. The severity
      of OC symptoms was assessed with the Yale Brown Obsessive-Compulsive Scale (Y
      BOCS). Fifty-eight patients participated in subsequent assessments comparing
      schizophrenia severity (Positive and Negative Syndrome Scale) functional status
      (Social and Occupational Functioning Scale) and resource utilization (psychiatric
      hospitalization) of OC (N=21) and non-OC (N=37) patients. RESULTS: Thirty percent
      of patients exhibited two or more OC symptoms, and 19% had at least moderate OC
      symptoms (Y-BOCS score >or= 16). Twenty-three percent met full DSM-IV criteria
      for OCD. There were no differences observed between the OC and non-OC groups on
      any of the clinical outcomes. OC symptoms were developed prior to the onset of
      schizophrenia in only 28% of patients. CONCLUSIONS: Nearly one-third of patients
      exhibited clinically significant OC symptoms in this systematic, cross-sectional
      assessment. However, OC symptoms did not appear to impact the clinical outcome of
      patients. In most cases, OC symptoms began concurrently with or after the onset
      of the psychotic disorder. Studies are needed to define the relevance and
      pathological basis for the co-occurrence of OC symptoms in persons with
      schizophrenia.

PMID- 15949664
TI  - Psychophysiological evaluation of stigma towards schizophrenia.
AB  - Stigma is a potentially destructive phenomenon that may result in negative
      consequences for individuals diagnosed or labeled as having a mental illness.
      Several recent studies suggest that contact with various stigmatized out-group
      members result in psychophysiological reactions indicative of negative affect. It
      is unclear whether such reactions extend to encounters with individuals with
      mental illness. Participants imagined interacting with individuals labeled or
      unlabeled as having schizophrenia, while corrugator supercilii (brow) EMG, palmer
      skin conductance, and heart rate activity were monitored. Participants were 15
      males and 20 females mainly African American students between the ages of 18 and
      28 who attended a historically black university in the Southeastern region of the
      United States. Participants reported higher SUDS ratings and exhibited higher
      brow muscle tension during imagery with labeled than non-labeled individuals.
      Psychophysiological reactivity predicted global self-reported attitudes of stigma
      towards labeled individuals. The findings suggest that one reason why individuals
      avoid individuals with mental illness is physiological arousal, which is likely
      experienced as negative.

PMID- 15949665
TI  - Social class of origin, lost potential, and hopelessness in schizophrenia.
AB  - Among schizophrenia patients, young (under 35 years of age), men within the first
      5 years of illness onset are a particularly vulnerable group for suicide. It has
      been hypothesized that suicide in this group is related to the experience of the
      loss of functioning from pre- to post-morbid state and/or to the discrepancy
      between high expectations and actual achievements. The purpose of this study is
      to initiate the deconstruction of the sociocultural context of family of origin
      among schizophrenia patients as a means of better understanding "lost potential"
      and its relationship to indices of suicide risk such as hopelessness. Eighteen
      young, White, unemployed male schizophrenia patients were asked to indicate what
      job they thought they would have before the onset of schizophrenia and completed
      depression and hopelessness questionnaires. The results suggest that job
      expectation was significantly positively correlated with socioeconomic status of
      family of origin and patients' depression and hopelessness. The theoretical and
      treatment (especially with respect to vocational services) implications are
      discussed. Finally, this study formally introduces the concept that "advantaged"
      socioeconomic status may confer paradoxical disadvantage in coping with the
      vocational losses consequent to schizophrenia.

PMID- 15949666
TI  - Advanced paternal age associated with an elevated risk for schizophrenia in
      offspring in a Japanese population.
AB  - OBJECTIVE: Advanced paternal age at birth as a risk for schizophrenia in the
      adult offspring has been reported in previous studies exclusively conducted in
      Western countries and Israel. The question has arisen whether this finding could
      be replicated in countries with socially and culturally different attitudes
      toward marriage, including factors such as age at marriage. To address this
      question, we conducted a case-control study of a Japanese population. METHODS:
      The subjects were representative inpatients with a DSM-IV diagnosis of
      schizophrenia. Unrelated healthy volunteers were recruited as control subjects.
      This study was conducted as one of a series of the projects by use of "The Mother
      and Child Health Handbooks (MCHHs)," from which information on parental
      characteristics around the time of birth, including parental ages at birth, had
      been extracted and recorded on computer. RESULTS: Ninety-nine subjects with
      schizophrenia and 381 healthy control subjects enrolled for the study. Advanced
      paternal, but not maternal, age was associated with an elevated risk for
      schizophrenia. Reproducibility of the association across different cultures is
      suggestive of a causal link.

PMID- 15949667
TI  - Dietary fatty acid and antioxidant intake in community-dwelling patients
      suffering from schizophrenia.
AB  - INTRODUCTION: Brain phospholipids are uniquely rich in polyunsaturated fatty
      acids (PUFAs). Most PUFAs such as alpha-linolenic acid 18:3(n-3),
      eicosapentaenoic acid 20:5(n-3), and docosahexaenoic acid 22:6(n-3) are essential
      and must be provided through the diet. PUFAs are also very sensitive to oxidative
      stress. Decreased essential fatty acid content has been observed in cell
      membranes of various tissue types of schizophrenia patients, including neural
      cell membranes. A number of mechanisms may account for these deficits, such as
      inadequate dietary supply or increased oxidation. It is known that patients with
      schizophrenia make poor dietary choices. However, whether their dietary fatty
      acid or antioxidant intake is insufficient and contributes to the observed
      deficiencies has not been assessed. METHODS: After obtaining informed consent, a
      24-h diet recall was administered to elicit nutritional information in 146
      outpatients with schizophrenia. Intake of fatty acids and antioxidants including
      vitamins A, C, and E was compared to U.S. population standards according to the
      National Health and Nutrition Examination Survey Cycle III (NHANES III) results.
      RESULTS: Saturated and polyunsaturated fatty acid (PUFA) intake was significantly
      higher in schizophrenia patients than in controls (p<or=0.05; p<or=0.005,
      respectively). No differences were found with regard to dietary intake of gamma
      linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3) and docosahexaenoic
      acid (22:6n-3). Similarly, antioxidant intake was not different between
      schizophrenia patients and controls. CONCLUSION: The observed cell membrane
      deficits in PUFA and essential fatty acid content do not appear to derive from
      decreased dietary supply. Rather, intrinsic membrane phospholipid metabolism
      abnormalities may be causative. Overall increased fat intake in schizophrenia
      patients may contribute to the development of serious medical comorbidities, and
      further advance the risk for cumbersome metabolic side effects of antipsychotic
      treatment such as new-onset diabetes mellitus.

PMID- 15949668
TI  - A double-blind placebo-controlled cross over trial of bupropion in smoking
      reduction in schizophrenia.

PMID- 15949670
TI  - Strategies to increase central N-acetyl aspartylglutamate: a potential treatment
      for schizophrenia and bipolar disorders.

PMID- 15949669
TI  - Reappearance of tardive dystonia with olanzapine treated with clozapine.

PMID- 15949671
TI  - Analysis of PIK3C3 promoter variant in African-Americans with schizophrenia.

PMID- 15949672
TI  - An association study of the KPNB3 locus with schizophrenia in a Chinese
      population.

PMID- 15949673
TI  - Carotenoids: risk or benefit for health.

PMID- 15949674
TI  - Challenges to understanding and measuring carotenoid bioavailability.
AB  - Carotenoids are an excellent example of where poor understanding of food
      structure, complexity of behaviour during digestion, and inter-individual
      differences in response, lead to misinterpretation of study results. Four
      challenges associated with understanding and measuring carotenoid bioavailability
      are discussed: release of carotenoids from food structure and processing into an
      absorbable form (bioaccessibility), passage of carotenoids from gut lumen into
      the body (absorption), interpreting plasma response and inter-individual
      variation. Bioaccessibility of carotenoids is governed by characteristics of the
      food matrix, which affect the efficiency of physical, enzymic and chemical
      digestion. Carotenoids used as colorants are likely to be better absorbed because
      of the form in which they are dispersed in food. Extent of absorption of
      carotenoid supplements will depend on the proximity of dosing to the consumption
      of a fat-containing meal. Release of carotenoids from food plants occurs only
      when the plant cell is fractured and this occurs only during food preparation,
      processing and/or mastication, not during digestion. Following release from the
      food matrix, the major limiting factor is solubility of carotenoids in digesta.
      Absorption studies are best carried out by measuring chylomicron carotenoid
      excursion, with modelling of chylomicron turnover rate. In this way, inter
      individual differences in lipoprotein metabolism can, in part, be taken into
      account before formulating conclusions on the rate and extent of absorption.

PMID- 15949675
TI  - Bioactivity and protective effects of natural carotenoids.
AB  - Carotenoids comprise a class of natural fat-soluble pigments which are found in
      numerous fruits and vegetables. The consumption of a diet rich in carotenoids has
      been epidemiologically correlated with a lower risk for several diseases. The
      antioxidant activity of carotenoids and biochemical properties influencing
      signaling pathways have been discussed as basic mechanisms of prevention.
      Conflicting data from intervention studies with beta-carotene to prevent cancers
      and cardiovascular disorders have challenged the concept. However, there is
      convincing evidence that carotenoids are important components of the antioxidant
      network. Photooxidative damage is suggested to be involved in the
      pathobiochemistry of several diseases affecting the skin and the eye, and
      carotenoids may protect light-exposed tissues. Lutein and zeaxanthin are the
      predominant carotenoids of the retina and are considered to act as
      photoprotectants preventing retinal degeneration. The unique distribution,
      localization and high levels of both carotenoids within the macula lutea as well
      as their physicochemical properties make them suitable candidates for
      photoprotection. beta-Carotene is used as an oral sun protectant for the
      prevention of sunburn and has been shown to be effective either alone or in
      combination with other carotenoids or antioxidant vitamins. Protective effects
      are also achieved with a diet rich in lycopene.

PMID- 15949676
TI  - Carotenoids as modulators of lipid membrane physical properties.
AB  - Carotenoids are a group of pigments present both in the plant and animal
      kingdoms, which play several important physiological functions. The protection
      against active oxygen species, realised via the quenching of excited states of
      photosensitizing molecules, quenching of singlet oxygen and scavenging of free
      radicals, is one of the main biological functions of carotenoids. Several recent
      research indicate that the protection of biomembranes against oxidative damage
      can be also realised via the modification of the physical properties of the lipid
      phase of the membranes. This work presents an overview of research on an effect
      of carotenoids on the structural and dynamic properties of lipid membranes
      carried out with the application of different techniques such as Electron
      Paramagnetic Resonance, Nuclear Magnetic Resonance, Differential Scanning
      Calorimetry, X-ray diffractometry, monomolecular layer technique and other
      techniques. It appears that, in most cases, polar carotenoids span lipid bilayer
      and have their polar groups anchored in the opposite polar zones of the membrane.
      Owing to the van der Waals interactions of rigid rod-like molecules of carotenoid
      and acyl chains of lipids, pigment molecules rigidify the fluid phase of the
      membranes and limit oxygen penetration to the hydrophobic membrane core
      susceptible to oxidative degradation.

PMID- 15949677
TI  - Synergistic effects of zeaxanthin and its binding protein in the prevention of
      lipid membrane oxidation.
AB  - There is growing evidence that high levels of the macular xanthophyll carotenoids
      lutein and zeaxanthin may be protective against visual loss due to age-related
      macular degeneration, but the actual mechanisms of their protective effects are
      still poorly understood. We have recently purified, identified and characterized
      a pi isoform of glutathione S-transferase (GSTP1) as a zeaxanthin-binding protein
      in the macula of the human eye which specifically and saturably binds to the two
      forms of zeaxanthin endogenously found in the foveal region. In this report, we
      studied the synergistic antioxidant role of zeaxanthin and GSTP1 in egg yolk
      phosphatidylcholine (EYPC) liposomes using hydrophilic 2,2'-azobis(2-methyl
      propionamidine) dihydrochloride (AAPH) and lipophilic 2,2'-azobis(2,4
      dimethylvaleronitrile) (AMVN) as lipid peroxyl radical generators. The two
      zeaxanthin diastereomers displayed synergistic antioxidant effects against both
      azo lipid peroxyl radical generators when bound to GSTP1. In the presence of
      GSTP1, nondietary (3R,3'S-meso)-zeaxanthin was observed to be a better
      antioxidant than dietary (3R,3'R)-zeaxanthin. This effect was found to be
      independent of the presence of glutathione. Carotenoid degradation profiles
      indicated that the zeaxanthin diastereomers in association with GSTP1 were more
      resistant to degradation which may account for the synergistic antioxidant
      effects.

PMID- 15949678
TI  - Towards a better understanding of carotenoid metabolism in animals.
AB  - Vitamin A derivatives (retinoids) are essential components in vision; they
      contribute to pattern formation during development and exert multiple effects on
      cell differentiation with important clinical implications. All naturally
      occurring vitamin A derives by enzymatic oxidative cleavage from carotenoids with
      pro-vitamin A activity. To become biologically active, these plant-derived
      compounds must first be absorbed, then delivered to the site of action in the
      body, and metabolically converted to the real vitamin. Recently, molecular
      players of this pathway were identified by the analysis of blind Drosophila
      mutants. Similar genome sequences were found in vertebrates. Subsequently, these
      homologous genes were cloned and their gene products were functionally
      characterized. This review will summarize the advanced state of knowledge about
      the vitamin A biosynthetic pathway and will discuss biochemical, physiological,
      developmental and medical aspects of carotenoids and their numerous derivatives.

PMID- 15949679
TI  - Beta-carotene uptake and metabolism in human lung bronchial epithelial cultured
      cells depending on delivery vehicle.
AB  - Beta-carotene (BC) could have a protective or pro-carcinogenic role in lung
      cancer, and cell culture systems are important to evaluate it. Nevertheless, the
      delivery of the hydrophobic BC to cells is difficult. Different vehicles have
      been used such as liposomes, tetrahydrofuran and serum lipoproteins, but
      presenting different problems. Water dispersible beadlets containing BC are a
      good choice and can produce the greatest BC uptake when compared to the above
      vehicles, but other beadlet components could alter the results. Dimethylsulfoxide
      (DMSO) could be a good alternative since it has low toxicity and it enhances the
      penetration of substances across biologic membranes. We aimed to characterize an
      appropriate model for delivering all-trans-BC to lung cells in culture and
      knowing its metabolism. All-trans-BC 5 microM was administered to BEAS-2B cells
      in beadlets or DMSO, and medium and cell samples were taken at different times.
      The levels of BC and its main isomers and metabolites were determined by HPLC.
      All-trans-BC reached the same levels in the medium (about 3.5 microM) either when
      supplied in beadlets or in DMSO, and, with beadlets, 13-cis-BC was also detected.
      However the amount of all-trans-BC taken up by the cells was the triple when
      delivered by DMSO. With both vehicles, intracellular all-trans-BC levels reached
      its maximum after 24 h of treatment, remaining equal after 72 h. The 9-cis and 13
      cis isomers of BC, and oxidized metabolites, were also detected in the cells
      although in smaller proportion than all-trans-BC, especially with DMSO. An LDH
      assay did not suggest toxicity of beadlets, DMSO or BC itself. In conclusion,
      DMSO seems the most appropriate vehicle for delivering BC to lung cells in vitro,
      and we present a model that allows studying the effects of BC and its metabolism
      in the lung human BEAS-2B cell line.

PMID- 15949680
TI  - Beta-carotene and the application of transcriptomics in risk-benefit evaluation
      of natural dietary components.
AB  - Beta-carotene is a natural food component that is present in fruits and
      vegetables and is also used as a food colorant and a supplement. Beta-carotene is
      an anti-oxidant and a source of vitamin A. It is endowed with health beneficial
      properties, but a number of studies showed that with high intakes it may increase
      the risk for lung cancer in at risk individuals (heavy smokers, asbestos workers
      and alcohol users). To establish the window of benefit, it is necessary to
      identify early markers of effect and to obtain insight in the mechanism of action
      of beta-carotene, in the absence and presence of environmental risk factors.
      Genomics technologies are well suited to dissect the mechanisms of action and
      identify the markers of effect. Human cell lines can be used to analyse the
      effects of beta-carotene, but exposure studies with beta-carotene show that cell
      lines display a widely variant behaviour, which hampers translation to the in
      vivo situation in humans. Alternatively, animal studies can be used. Especially
      the ferret seems to be a good model, but little sequence information of this
      species is available. However, heterologous hybridization on human cDNA seems
      possible and provides and a new tool for molecular analysis of health effects of
      beta-carotene.

PMID- 15949681
TI  - Mechanisms of genomic and non-genomic actions of carotenoids.
AB  - Carotenoids are highly bioactive dietary compounds that have the potential to
      have significant effects on human health. It is becoming increasingly clear that
      the various biological effects that carotenoids exert could be driven via a
      number of different mechanisms. These include direct pro- and antioxidant
      effects, redox sensitive cell signalling, vitamin A signalling pathways and other
      as yet unidentified mechanisms. This article provides an overview of the known
      effects of carotenoids and discusses the use of model systems and functional
      genomic approaches further to elucidate their modes of action.

PMID- 15949682
TI  - Gene expression profiling identifies retinoids as potent inducers of macrophage
      lipid efflux.
AB  - Vitamin A and its naturally occurring derivatives 9-cis retinoic acid (9-cis RA)
      and all-trans retinoic acid (ATRA) exert a variety of biological effects
      including immunomodulation, growth, differentiation, and apoptosis of normal and
      neoblastic cells. In order to directly study the effects of these retinoids on
      macrophage gene expression and lipid metabolism, primary human monocytes and in
      vitro differentiated macrophages were stimulated with beta-carotene, 9-cis RA,
      and ATRA and global gene expression profiles were analyzed by Affymetrix DNA
      microarrays and differentially regulated genes were verified by quantitative
      TaqMan RT-PCR. Among others, we have identified a strong up-regulation of a
      cluster of genes involved in cholesterol metabolism including apolipoproteins
      (apoC-I, apoC-II, apoC-IV, apoE), the scavenger receptor CD36, steroid-27
      hydroxylase (CYP27A1), liver X receptor alpha (LXRalpha), and ATP-binding
      cassette transporters A1 (ABCA1) and G1 (ABCG1). Since the CYP27A1 gene displayed
      the strongest up-regulation on the mRNA level, we cloned various deletion
      constructs of the promoter region and analyzed the response to retinoids in
      macrophages. Thereby, a novel retinoic acid-responsive element could be located
      within 191 bp of the proximal CYP27A1 promoter. To further assess the functional
      consequences of retinoid receptor action, we carried out phospholipid and
      cholesterol efflux assays. We observed a strong induction of apoA-I-dependent
      lipid efflux in stimulated macrophages, implicating an important role for
      retinoids in cellular functions of macrophages.

PMID- 15949683
TI  - Induction of PXR-mediated metabolism by beta-carotene.
AB  - beta-carotene is the major carotenoid occurring in the human diet and in the
      human organism. Besides its function as pro-vitamin A, beta-carotene has been
      shown to be an activator of the human pregnan X receptor (PXR). PXR is mainly
      expressed in the liver/intestine and an inducer of enzymes involved in phase I,
      II and III metabolism. This review is focused on the evaluation of physiological
      and nutritional relevance of beta-carotene as an inducer of phase I enzymes in
      the human organism via PXR-mediated mechanisms. Beneficial and detrimental
      effects of beta-carotene on xenobiotica metabolism and metabolism of various
      other derivatives will be discussed.

PMID- 15949684
TI  - Cancer prevention by retinoids and carotenoids: independent action on a common
      target.
AB  - Virtually all human tumors are deficient in gap junctional communication (GJC)
      and the restoration of GJC by forced expression of connexins reduces indices of
      neoplasia. The expression of connexin 43 (Cx43) is upregulated by cancer
      preventive retinoids and carotenoids which correlates with the suppression of
      carcinogen-induced transformation in 10T1/2 cells. However, the molecular
      mechanism for upregulated expression is poorly understood. The retinoic acid
      receptor antagonist, Ro 41-5253, suppressed retinoid-induced Cx43 protein
      expression in 10T1/2 cells and the induction of a Cx43 luciferase reporter
      construct in F9 cells, but did not suppress protein expression or reporter
      activity induced by the non-pro-vitamin A carotenoid astaxanthin. In contrast,
      Cx43 induction by astaxanthin, but not by a RAR-specific retinoid, was inhibited
      by GW9662, a PPAR-gamma antagonist. Neither compound required protein synthesis
      for the induction of Cx43 mRNA, nor was the 5.0 h half-life of Cx43 mRNA altered,
      indicating direct transcriptional activation. The responsive region was found
      within -158 bp and +209 bp of the transcription start site. Site directed
      mutagenesis of a GC-box in this region increased basal levels of transcription
      and loss of retinoid responsiveness. Simultaneous treatment with a retinoid and
      beta-carotene or astaxanthin resulted in supra-additive Cx43 expression, again
      indicating separate mechanisms of gene regulation.

PMID- 15949685
TI  - Beta-carotene interaction with NNK in the AJ-mouse model: effects on cell
      proliferation, tumor formation and retinoic acid responsive genes.
AB  - We studied the influence of beta-carotene on the tobacco smoke carcinogen 4-(N
      Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumor
      development in the A/J-mouse model. The normally low beta-carotene absorption was
      facilitated with a diet enriched in fat and bile salt, resulting in plasma and
      lung tissue levels similar to humans. beta-Carotene enhanced NNK-induced early
      bronchial cell proliferation, however, this effect was not predictive for later
      tumor development. Tumor multiplicity was not significantly affected by beta
      carotene, neither in carcinogen-initiated nor in uninitiated mice, and regardless
      of dose and time point of supplementation during tumor development. RARbeta
      isoform and CYP26 gene expression levels analyzed by quantitative RT-PCR were
      weakly, but significantly, inversely correlated and showed evidence for altered
      retinoid signaling and catabolism in the lungs of NNK-initiated, beta-carotene
      supplemented mice. However, this interaction did not translate into enhanced
      tumor multiplicity. These results indicate that impaired retinoid signaling is
      not likely a key factor in lung tumorigenesis in this mouse model.

PMID- 15949686
TI  - Different effect of beta-carotene on proliferation of prostate cancer cells.
AB  - It was shown that high doses of beta-carotene (>30 microM) decrease proliferation
      of prostate cancer cells in vitro. However, it is rather doubtful whether such
      concentration of beta-carotene is really accessible at cellular level. We studied
      the effect of 3 and 10 microM beta-carotene on proliferation and gene expression
      in LNCaP and PC-3 prostate cancer cell lines. Beta-carotene--more efficiently
      absorbed from medium by androgen-sensitive LNCaP cells--increased proliferation
      of LNCaP cells whereas it had weaker effect on PC-3 cells. Initial global
      analysis of expression of genes in both cell lines treated with 10 microM beta
      carotene (Affymetrix HG-U133A) showed remarkable differences in number of
      responsive genes. Their recognition allows for conclusion that differences
      between prostate cancer cell lines in response to beta-carotene treatment are due
      to various androgen sensitivities of LNCaP and PC-3 cells. Detailed analysis of
      expression of selected genes in beta-carotene treated LNCaP cells at the level of
      mRNA and protein indicated that the observed increase of proliferation could have
      been the result of slight induction of a few genes affecting proliferation (c
      myc, c-jun) and apoptosis (bcl-2) with no significant effect on major cell cycle
      control genes (cdk2, RB, E2F-1).

PMID- 15949687
TI  - Role of lycopene and tomato products in prostate health.
AB  - Epidemiological evidence associating the decreased risk of prostate cancer with
      frequent consumption of tomato products inspired us to conduct a small
      intervention trial among patients diagnosed with prostate adenocarcinoma. Tomato
      sauce pasta was consumed daily for 3 weeks before their scheduled prostatectomy,
      and biomarkers of tomato intake, prostate cancer progression and oxidative DNA
      damage were followed in blood and the available prostate tissue. The whole food
      intervention was so well accepted by the subjects that the blood lycopene (the
      primary carotenoid in tomatoes responsible for their red color) doubled and the
      prostate lycopene concentration tripled during this short period. Oxidative DNA
      damage in leukocytes and prostate tissues was significantly diminished, the
      latter mainly in the tumor cell nuclei, possibly due to the antioxidant
      properties of lycopene. Quite surprising was the decrease in blood prostate
      specific antigen, which was explained by the increase in apoptotic death of
      prostate cells, especially in carcinoma regions. Prostate cancer cell cultures
      (LNCaP) were also sensitive to lycopene in growth medium, which caused an
      increased apoptosis and arrested the cell cycle. A possible explanation of these
      promising results may reside in lycopene effects on the genes governing the
      androgen stimulation of prostate growth, cytokines and on the enzymes producing
      reactive oxygen species, all of which were recently discovered by nutrigenomic
      techniques. Other phytochemicals in tomato may act in synergy with lycopene to
      potentiate protective effects and to help in the maintenance of prostate health.

PMID- 15949688
TI  - The effect of beta-carotene and its derivatives on cytotoxicity, differentiation,
      proliferative potential and apoptosis on the three human acute leukemia cell
      lines: U-937, HL-60 and TF-1.
AB  - The influence of beta-carotene (BC) and its derivatives on differentiation,
      proliferation and apoptosis in three human acute leukemia cell lines was studied.
      We investigated: (i) the cellular uptake of BC, (ii) the cytotoxicity, (iii) the
      effect on cell cycle progression and/or apoptosis. The dose- and time-dependent
      pattern of cellular BC uptake in all studied cell lines was seen. We did not
      observe any cytotoxic effect of BC and ATRA in the chosen concentrations. There
      was only limited effect of BC on gene expression. The microarrray analysis of U
      937 cell line exposed to BC for 72 h showed an increased expression of BAX gene.
      This finding was confirmed by real-time Q-PCR analysis, and supported by a flow
      cytometry apoptosis tests. We did not observe any influence of studied components
      on cellular proliferation. The induction of differentiation after incubation with
      ATRA in HL-60 cells was noted. The induction of cellular apoptosis by BC was seen
      in all studied cell lines. We demonstrated that BC used in the concentrations
      achievable in vivo does not affect the proliferation and differentiation process
      of the studied leukemic cell lines, but can influence and enhance the apoptosis
      by modulating the expression of the regulatory genes.

PMID- 15949689
TI  - Can beta-carotene regulate cell growth by a redox mechanism? An answer from
      cultured cells.
AB  - Many studies suggest a protective role of beta-carotene against cancer. However,
      the ATBC and the CARET trials have shown that beta-carotene increases the
      incidence of lung cancer in heavy smokers and asbestos workers. To explain this
      paradox, it can be hypothesized that beta-carotene modulates intracellular redox
      status and through this mechanism, it affects redox-sensitive molecular pathways
      involved in the regulation of cell cycle progression and apoptosis. Studies
      conducted in cultured cells seem to confirm such a hypothesis. At low
      concentrations, the carotenoid may serve as an antioxidant, inhibiting free
      radical production, while at relatively high concentrations and/or in the
      presence of a chronic oxidative stress (i.e. smoke), it may behave as a
      prooxidant, propagating free radical-induced reactions, consuming endogenous
      antioxidants and inducing DNA oxidative damage. In this context, it may regulate
      cell growth and death by the modulation of redox-sensitive genes and
      transcription factors.

PMID- 15949690
TI  - Proangiogenic activity of beta-carotene is coupled with the activation of
      endothelial cell chemotaxis.
AB  - Endothelial cells play an important role in angiogenesis (formation of new
      vessels from preexisting ones), which is essential for organogenesis, tissue
      remodeling but also inflammatory response, carcinogenesis in all periods of our
      life. Beta-carotene (BC) in non-toxic concentrations (up to 3 microM) had no
      detectable effect on HUVECs (human umbilical vein endothelial cells)
      proliferation or apoptosis, despite significant changes of the expression
      patterns of pro- and anti-apoptotic genes. However beta-carotene did not change
      the tubulogenic activity of HUVEC in the in vitro angiogenesis model, it potently
      accelerated the bFGF-induced development of microcapillaries, as well as the
      migration of endothelial cells, in matrigel plug injected subcutaneously to mice.
      Potent activation of endothelial cell migration in the in vitro model of
      chemotaxis was also observed. According to the microarray data, genes involved in
      cell/cell and cell/matrix adhesion, matrix reorganization, activation of
      chemotaxis, the G-protein regulated intracellular signaling as well as genes
      involved in the rapid remodeling of protein cytoskeleton were the most affected
      by BC in HUVEC. We conclude that beta-carotene in the physiological concentration
      range stimulates early steps of angiogenesis by the activation of cellular
      migration as well as matrix reorganization and decrease of cell adhesion.

PMID- 15949691
TI  - Embryonic stem cells for basic research and potential clinical applications in
      cardiology.
AB  - Embryonic stem (ES) cells are pluripotent, possessing the unique property to
      differentiate into any somatic cell type while retaining the ability to
      proliferate indefinitely. Due to their ability to recapitulate embryonic
      differentiation, ES cells are an ideal tool to study the process of early
      embryogenesis in vitro. Signalling cascades and genes involved in differentiation
      can be easily studied, and functional genomics approaches aim to identify the
      regulatory networks underlying lineage commitment. Their unique ability to
      differentiate into any cell type make ES cells a prime candidate for cell
      replacement therapy (CRT) of various degenerative disorders. Results from various
      disease models are promising and have demonstrated their principal suitability as
      a therapeutic agent in diseases such as myocardial infarctions, diabetes mellitus
      and Parkinson's disease. Prior to clinical trials in humans, two issues remain to
      be solved: due to their high proliferative potential, ES cells can form
      teratocarcinomas in the recipient, and depending on the source of the cells, ES
      cell grafts may be rejected by the host organism. This review discusses the
      current state of basic ES cell research with a focus on cardiac differentiation
      and gives an overview of their use in CRT approaches.

PMID- 15949692
TI  - Retinoic acid modulates the retinoblastoma protein during adipocyte terminal
      differentiation.
AB  - Terminal differentiation is characterized by a permanent withdrawal of cells from
      the cell cycle. Retinoblastoma protein (RB) has been involved in cell cycle
      progression. Accumulating evidence also implicates RB in the promotion of
      differentiation of many cell types. We present new insights into the role of RB
      and other cell cycle regulatory proteins in adipocyte differentiation and on the
      role of retinoic acid (RA) in the regulation of the latter process. It is shown
      that RA reduces RB expression and enhances RB phosphorylation by a mechanism that
      involves down-regulation of the cyclin-dependent kinase inhibitor (CKI)
      p21(Cip1), having this fact as important consequences for both the cell cycle
      progression and the adipocyte differentiation process. The effects of RA result
      in the blockage of adipogenesis, but may also favor the retention of a pool of
      adipose cells able to re-enter the cell cycle, which may be important for the
      developmental dynamics of adipose tissue in vivo. In addition, these results
      reinforce the idea that there is a cross-talk between the cell cycle machinery
      and the adipocyte differentiation machinery that can be modulated by external
      signals, including nutrients.

PMID- 15949694
TI  - Regulation of adipocyte differentiation and function by polyunsaturated fatty
      acids.
AB  - A diet enriched in PUFAs, in particular of the n-3 family, decreases adipose
      tissue mass and suppresses development of obesity in rodents. Although several
      nuclear hormone receptors are identified as PUFA targets, the precise molecular
      mechanisms underlying the effects of PUFAs still remain to be elucidated. Here we
      review research aimed at elucidating molecular mechanisms governing the effects
      of PUFAs on the differentiation and function of white fat cells. This review
      focuses on dietary PUFAs as signaling molecules, with special emphasis on
      agonistic and antagonistic effects on transcription factors currently implicated
      as key players in adipocyte differentiation and function, including peroxisome
      proliferator activated receptors (PPARs) (alpha, beta and gamma), sterol
      regulatory element binding proteins (SREBPs) and liver X receptors (LXRs). We
      review evidence that dietary n-3 PUFAs decrease adipose tissue mass and suppress
      the development of obesity in rodents by targeting a set of key regulatory
      transcription factors involved in both adipogensis and lipid homeostasis in
      mature adipocytes. The same set of factors are targeted by PUFAs of the n-6
      family, but the cellular/physiological responses are dependent on the
      experimental setting as n-6 PUFAs may exert either an anti- or a proadipogenic
      effect. Feeding status and hormonal background may therefore be of particular
      importance in determining the physiological effects of PUFAs of the n-6 family.

PMID- 15949693
TI  - Effects of retinoic acid administration and dietary vitamin A supplementation on
      leptin expression in mice: lack of correlation with changes of adipose tissue
      mass and food intake.
AB  - Retinoic acid (RA) administration and chronic vitamin A supplementation were
      reported to inhibit adipose tissue leptin expression in rodents, but the impact
      of this effect on food intake and its relationship with changes of body adiposity
      was not analyzed. Here, we have studied the effects of RA administration at three
      different doses on body weight, adipose tissue mass, food intake, adipose tissue
      leptin expression and circulating leptin levels in NMRI mice; the effects of
      chronic vitamin A supplementation with a 40-fold excess retinyl palmitate on the
      same parameters in NMRI and C57BL/6J mice; and the effects of RA and retinoid
      receptors agonists on leptin expression in brown and white adipocyte cell model
      systems. The results show that vitamin A down-regulates leptin expression in
      white and brown adipose tissue and circulating leptin levels independently of
      changes of adipose tissue mass and, for the first time to our knowledge, that
      this effect does not correlate with increased food intake. They also demonstrate
      a direct inhibitory effect of RA on leptin expression in both white and brown
      adipocyte cell cultures, and constitute first proof of the involvement of both RA
      receptors (RARs) and rexinoid receptors (RXRs) in this effect. Reduction of
      leptin levels by specific nutrients is of potential interest from a clinical
      point of view.

PMID- 15949695
TI  - Fatty acids and expression of adipokines.
AB  - Adipose tissue has been recognised as the quantitatively most important energy
      store of the human body for many years, in addition to its functions as
      mechanical and thermic insulator. In mammals, the adipose organ is localised in
      several depots including white as well as brown adipose tissues. The largest
      depots are found subcutaneously and in the abdominal region. Several secretory
      proteins are synthesised in adipose tissue including leptin, resistin,
      adiponectin, tumor necrosis factor (TNFalpha), angiotensinogen, adipsin,
      acylation-stimulating protein, retinol-binding protein (RBP), interleukin (IL)
      1b, IL-6, IL-8, IL-10, plasminogen activator inhibitor-1 (PAI-1), fasting-induced
      adipose factor, fibrinogen-angiopoietin-related protein, metallothionein, tissue
      factor (TF), complement C3, fibronectin, haptoglobin, entactin/nidogen, collagen
      VI alpha 3, pigment epithelium-derived factor (PEDF), hippocampal cholinergic
      neurostimulating peptide (HCNP), neutrophil gelatinase-associated lipocalin
      (NGAL) and adiponutrin. Fatty acids may influence the expression of adipokines
      like leptin, resistin or adiponectin directly by interaction with transcription
      factors, or indirectly via unknown mechanisms possibly linked to fatty acid
      oxidation, synthesis or storage. Because fatty acids are the main components of
      adipose tissue, it is of essential interest to clarify the biological effects of
      different types of fatty acids on the expression of relevant adipokines.

PMID- 15949696
TI  - PPARgamma in the control of brown adipocyte differentiation.
AB  - The effects of fatty acids and retinoic acid (carotene) on brown adipose tissue
      differentiation are mediated by activation of the transcription factors PPARgamma
      and PPARalpha in combination with RXR. There is good support for the idea that
      activated PPARgamma promotes adipogenesis also in brown adipose tissue. However,
      the issue is more complex concerning the full differentiation to the brown
      adipocyte phenotype, particularly the expression of the brown-fat-specific marker
      UCP1. The effect of norepinephrine on PPARgamma gene expression, at least in
      vitro, is negative, PPARgamma-ablated brown adipose tissue can express UCP1, and
      PGC-1alpha coactivates other transcription factors (including PPARalpha); thus,
      the significance of PPARgamma for the physiological control of UCP1 gene
      expression is not settled. However, importantly, the effects of PPAR agonists
      demonstrate the existence of a pathway for brown adipose tissue recruitment that
      is not dependent on chronic adrenergic stimulation and may be active in
      recruitment conditions such as prenatal and prehibernation recruitment. The
      ability of chronic PPARgamma agonist treatment to promote the occurrence of brown
      fat features in white adipose tissue-like depots implies a role in anti-obesity
      treatment, but this will only be effective if the extra thermogenic capacity is
      activated by adrenergic stimulation.

PMID- 15949697
TI  - Roles of PPAR delta in lipid absorption and metabolism: a new target for the
      treatment of type 2 diabetes.
AB  - Peroxisome proliferator-activated receptors (PPARs) are lipid-activated
      transcription factors exerting several functions in development and metabolism.
      PPARalpha, activated by polyunsaturated fatty acids and fibrates, is implicated
      in regulation of lipid metabolism, lipoprotein synthesis and metabolism and
      inflammatory response in liver and other tissues. PPARgamma plays important roles
      in regulation of proliferation and differentiation of several cell types,
      including adipose cells. Its activation by thiazolidinediones results in insulin
      sensibilization and antidiabetic action. Until recently, the physiological
      functions of PPARdelta remain elusive. The utilization of specific agonists and
      of appropriate cellular and animal models revealed that PPARdelta has an
      important role in metabolic adaptation of several tissues to environmental
      changes. Treatment of obese animals by specific PPARdelta agonists results in
      normalization of metabolic parameters and reduction of adiposity. The nuclear
      receptor appeared to be implicated in the regulation of fatty acid burning
      capacities of skeletal muscle and adipose tissue by controlling the expression of
      genes involved in fatty acid uptake, beta-oxidation and energy uncoupling.
      PPARdelta is also implicated in the adaptive metabolic response of skeletal
      muscle to endurance exercise by controlling the number of oxidative myofibers.
      Given the results obtained with animal models, PPARdelta agonists may have
      therapeutic usefulness in metabolic syndrome by increasing fatty acid consumption
      in skeletal muscle and adipose tissue.

PMID- 15949698
TI  - Anti-diabetic effect of ginsenoside Re in ob/ob mice.
AB  - We evaluated the anti-diabetic effects of ginsenoside Re in adult male C57BL/6J
      ob/ob mice. Diabetic ob/ob mice with fasting blood glucose levels of
      approximately 230 mg/dl received daily intraperitoneal injections of 7, 20 and 60
      mg/kg ginsenoside Re for 12 consecutive days. Dose-related effects of ginsenoside
      Re on fasting blood glucose levels were observed. After the 20 mg/kg treatment,
      fasting blood glucose levels were reduced to 188+/-9.2 and 180+/-10.8 mg/dl on
      Day 5 and Day 12, respectively (both P<0.01 compared to vehicle group, 229+/-9.5
      and 235+/-13.4 mg/dl, respectively). The EC(70) of ginsenoside Re was calculated
      to be 10.3 mg/kg and was used for subsequent studies. Consistent with the
      reduction in blood glucose, there were significant decreases in both fed and
      fasting serum insulin levels in mice treated with ginsenoside Re. With 12 days of
      ginsenoside treatment, glucose tolerance of ob/ob mice increased significantly,
      and the area under the curve for glucose decreased by 17.8% (P<0.05 compared to
      vehicle treatment). The hypoglycemic effect of the ginsenoside persisted even at
      3 days of treatment cessation (blood glucose levels: 198+/-13.1 with ginsenoside
      treatment vs. 253+/-20.3 mg/dl with vehicle, P<0.01). There were no significant
      changes in body weight or body temperature. Preliminary microarray analysis
      revealed differential expression of skeletal muscle genes associated with lipid
      metabolism and muscle function. The results suggest that ginsenoside Re may prove
      to be useful in treating type 2 diabetes.

PMID- 15949699
TI  - Up-regulation of mitogen activated protein kinases in mdx skeletal muscle
      following chronic treadmill exercise.
AB  - Dystrophin, a product of the Duchenne muscular dystrophy gene, is a cytoskeletal
      protein of skeletal and cardiac muscle fibers. Dystrophin-deficient muscle fibers
      are abnormally vulnerable to mechanical stress including physical exercise, which
      is a powerful stimulator of mitogen-activated protein kinases (MAPKs). To examine
      how treadmill exercise affects MAPK family members in dystrophin-deficient
      skeletal muscle, we subjected both mdx mice, an animal model for Duchenne
      muscular dystrophy, and C57BL/10 mice to treadmill exercise and examined the
      phosphorylated protein levels of extracellular-signal regulated kinase (ERK1/2),
      p38 MAPK and c-Jun N terminal kinase 1 and 2 (JNK1 and JNK2) in the gastrocnemius
      muscle. Phosphorylation of ERK1/2, p38 MAPK and JNK2, but not JNK1, increased
      more in the muscles of exercise trained mdx mice than in muscles of trained
      C57BL/10 or untrained mdx mice. These results show that physical exercise
      aberrantly up-regulates the phosphorylated form of ERK1/2, p38 MAPK and JNK2 in
      dystrophin-deficient skeletal muscle and that their up-regulation might play a
      role in the degeneration and regeneration process of dystrophic features.

PMID- 15949700
TI  - Effect of acetaminophen on the membrane anchoring of Na+, K+ATPase of rat renal
      cortical cells.
AB  - In previous works we reported that the administration of a toxic dose of
      acetaminophen (APAP) induces acute renal failure (ARF) and promotes changes on
      Na(+), K(+)ATPase distribution in renal proximal plasma membranes. In the present
      work, we analyzed if APAP could promote the dissociation of Na(+), K(+)ATPase
      from its membrane anchorage. The participation of calpain activation was also
      evaluated. We analyzed the Triton X-100 extractability of Na(+), K(+)ATPase in
      freshly isolated cortical cell suspensions incubated with different APAP
      concentrations (0.1, 1, 10 and 100 mM). Both alpha(1) and beta(1) subunits were
      studied by Western blot. APAP promoted the increment of both subunits abundance
      in the Triton-soluble fraction. Calpain activation was detected in the membrane
      fractions of cells incubated with APAP. Incubation with APAP 0.1, 1 and 10 mM did
      not promote an increment in LDH release compared with controls, while APAP 100 mM
      promoted an increased LDH release. Our results show that incubation of proximal
      cells with sublethal and lethal APAP concentrations promotes the detachment of
      Na(+), K(+)ATPase from its membrane anchoring. Inhibition of calpain activation
      by SJA 7029 protected against APAP-induced membrane damage but not against APAP
      induced increase of the Triton X-100 extractability of Na(+), K(+)ATPase.

PMID- 15949701
TI  - The effect of short-term kaempferol exposure on reactive oxygen levels and
      integrity of human (HL-60) leukaemic cells.
AB  - Flavonoids may be a principal contributor to the cancer preventative activity of
      fruit- and vegetable-rich diets and there is interest in their use as dietary
      supplements. However, there is potential conflict between the cytoprotective and
      cytotoxic activities of flavonoids, and their efficacy as anti-cancer agents is
      unresolved. Here, the integrity and survival of HL-60 promyelocytic leukaemia
      cells following short-term (90 min) exposure to the dietary abundant flavonoid
      kaempferol (1-100 microM) is reported. Supplementation initially decreased
      reactive oxygen levels but, paradoxically, a dose-dependent increase in single
      strand DNA breakage occurred. However, there was no increase in oxidised DNA
      purines or membrane damage. Following a 24-h recovery period in non-kaempferol
      supplemented media, DNA single-strand breakage had declined and kaempferol
      exposed and control cultures possessed similar reactive oxygen levels. A
      reduction in (3)H-thymidine incorporation occurred with > or =10 microM
      kaempferol. One hundred micromolar kaempefrol increased the proportion of cells
      in G(2)-M phase, the proportion of cells with a sub-G(1) DNA content and enhanced
      'active' caspase-3 expression but only induced a loss of mitochondrial membrane
      potential within a minority of cells. The relevance of induced DNA damage within
      a non-overtly oxidatively stressed environment to the disease preventative and
      therapeutic use of kaempferol is discussed.

PMID- 15949702
TI  - Expression of apolipoprotein AI mRNA in peripheral white blood cells of patients
      with alcoholic liver disease.
AB  - Because (i) changes in plasma and liver mRNA of apolipoprotein (apo) AI have been
      observed in patients with alcoholic liver disease, (ii) apo AI mRNA can be
      induced in non-hepatic tissues, and (iii) apolipoproteins expression is
      influenced by plasma colloid osmotic pressure (P(CO)) and viscosity (eta), we
      analyzed the Apo AI mRNA expression in the peripheral white blood cells (PWBC),
      P(CO), and eta in control volunteers (C), patients with liver cirrhosis (LC), and
      cirrhotic patients with superimposed alcoholic hepatitis (LC+AH). We found that
      apo AI mRNA is expressed in the PWBC in 20% of C and it is induced 1.5 fold in
      66.6% of LC and 1.95 fold in 85% of LC+AH. A significant decrease of P(CO) in LC
      and LC + AH (14.8 +/- 2.4 and 16.2 +/- 2.4 mm Hg, respectively) compared to C
      (27.9 +/- 2 mm Hg) was observed. By contrast, eta was mildly increased from
      1.7389 +/- 0.07 in C to 1.8022 +/- 0.154 in LC and 1.9030 +/- 0.177 in LC+AH. No
      significant correlation was found between P(CO) and eta with apo AI mRNA but with
      lipid profile. In conclusion, apo AI mRNA expression in PWBC is associated to
      liver disease severity and could be an indirect indicator of alcoholic liver
      damage.

PMID- 15949704
TI  - Apoptosis vs. necrosis: glutathione-mediated cell death during rewarming of rat
      hepatocytes.
AB  - Hypothermia induces injury in its own right, but the mechanisms involved in the
      cell damage are still unclear. The aim of this study was to test the effects that
      glutathione (GSH) depletion induces on cell death in isolated rat hepatocytes,
      kept at 4 degrees C for 20 h, by modulating intracellular GSH concentration with
      diethylmaleate and buthionine sulfoximine (DEM and BSO). Untreated hepatocytes
      showed Annexin V stained cells (AnxV(+)), scarce propidium iodide stained cells
      (PI(+)) and presented a low level of lactate dehydrogenase (LDH) leakage after 20
      h at 4 degrees C and rewarming at 37 degrees C. When DEM and BSO were added
      before cold storage, we observed a few AnXV(+) cells and an increase in PI(+)
      cells associated with LDH release in the incubation medium. Conversely, the
      addition of DEM and BSO only during rewarming caused a marked increase in cell
      death by apoptosis. Production of reactive oxygen species (ROS) and
      thiobarbituric acid species (TBARS), associated with a decrease in GSH
      concentrations, was higher when DEM and BSO were added before cold storage. Cells
      treated with DEM and BSO before cold storage showed lower ATP energy stores than
      hepatocytes treated with DEM and BSO only during rewarming. Pretreatment of
      hepatocytes with deferoxamine protected against apoptotic and necrotic morphology
      in conditions of GSH depletion. These results suggest that pretreatment of
      hepatocytes with DEM and BSO before cold storage induces necrosis, while the
      treatment of hepatocytes only during rewarming increases apoptosis. In both
      conditions, iron represents a crucial mediator of cell death.

PMID- 15949703
TI  - Suppressive effects of dietary curcumin on the increased activity of renal
      ornithine decarboxylase in mice treated with a renal carcinogen, ferric
      nitrilotriacetate.
AB  - Curcumin, a natural, biologically active compound extracted from rhizomes of
      Curcuma species, has been shown to act as a biological response modifier in
      various disorders. We have reported previously that the dietary supplementation
      of curcumin enhances the activities of antioxidant and phase II metabolizing
      enzymes in mice (M. Iqbal, S.D. Sharma, Y. Okazaki, M. Fujisawa, S. Okada,
      Dietary supplementation of curcumin enhances antioxidant and phase II
      metabolizing enzymes in ddY mice: possible role in protection against chemical
      carcinogenesis and toxicity, Pharmacol and Toxicol. 92 (2003) 33_38.) and
      inhibits ferric nitrilotriacetate (Fe-NTA) induced oxidative injury of lipids and
      DNA in vitro (M. Iqbal, Y. Okazaki, S. Okada, In vitro curcumin modulates Ferric
      Nitrilotriacetate (Fe-NTA) and hydrogen peroxide (H(2)O(2))-induced peroxidation
      of microsomal membrane lipids and DNA damage, Teratogenesis Carcinogenesis and
      Mutagenesis Supplement 23 (2003) 151-160.). In our present study, Fe-NTA, a known
      complete renal carcinogen, which generate ROS in vivo, was given
      intraperitoneally to mice and curcumin was tested for its ability to inhibits
      oxidative stress and the activity of ornithine decarboxylase (ODC) as well as
      histopathological changes in the kidney. Substantial changes in glutathione,
      antioxidant enzymes as well as changes in phase II metabolizing enzymes were
      observed in the kidney at 12 h after treatment with Fe-NTA (9.0 mg Fe/kg body
      weight). Effect of oxidative stress induced by Fe-NTA were also demonstrated by
      the increase in lipid peroxidation as monitored by formation of thiobarbituric
      acid-reactive substances and 4-hydroxy-2-nonenal (HNE)-modified proteins in
      kidney. Likewise, the level of protein carbonyl contents, an indicator of protein
      oxidation was also increased after Fe-NTA administration. However, the changes in
      these parameters were restored to normal in curcumin-pretreated mice. The ODC
      activity in the kidney was significantly increased by Fe-NTA, while the increased
      ODC activity induced by Fe-NTA was normalized in curcumin-pretreated mice. In
      addition, curcumin pretreatment almost completely prevented kidney biomolecules
      from oxidative damage and protected the tissue against observed histopathological
      alterations.

PMID- 15949705
TI  - Interaction between insulin (VNTR) and hepatic lipase (LIPC-514C>T) variants on
      the response to an oral glucose tolerance test in the EARSII group of young
      healthy men.
AB  - Insulin resistance is polygenic in origin, and can be observed at an early age.
      We have shown that variations in APOC3-482T>C and hepatic lipase (LIPC)-514C>T),
      individually (APOC3 alone) and interactively, modulate insulin and glucose levels
      after an OGTT in young healthy men participating in the European Atherosclerosis
      Research Study II (EARSII). Variation in the insulin gene (INS) variable number
      tandem repeat (VNTR) has been found to predispose to type 1 and type 2 diabetes.
      We have evaluated the HphI site 23 bp upstream of the INS gene (a surrogate
      marker for the VNTR) in EARSII (n=822), to determine if variation in INS
      contributes to insulin resistance. Carriers of the INS VNTR class III (HphI-)
      allele (frequency=0.29 (95%CI 0.27, 0.31)) had significantly higher 60-min
      insulin concentrations after the OGTT (P=0.014) and a marginally higher AUC
      insulin (P=0.07), compared to class I (HphI+) homozygotes. However, this effect
      on AUC insulin was modified by the level of physical activity, displaying
      significant gene:environment interaction (P=0.03). We tested for gene:gene
      interaction between the INS VNTR and both the LIPC-514C>T and APOC3-482T>C. While
      there was a significant interaction between INS VNTR and LIPC-514C>T on AUC
      glucose (P=0.013) and on AUC insulin (P=0.015), there was no interaction with
      APOC3-482T>C. Thus, despite a modest effect of the INS VNTR alone, the influence
      of this variant on insulin sensitivity was modified by gene:environment and
      gene:gene interactions, illustrating the biological complexity of insulin
      resistance.

PMID- 15949706
TI  - Skeletal muscles, heart, and lung are the main sources of oxygen radicals in old
      rats.
AB  - The aim of this study was to compare rat tissues with respect to their reactive
      oxygen and nitrogen species (RONS) generating activities as a function of age. We
      quantified the RONS generation in vivo in young (6 months) and in old (30 months)
      male Sprague-Dawley rats using the recently developed spin trap 1-hydroxy-3
      carboxy-pyrrolidine, applied intravenously. This spin trap reacts with superoxide
      radical and peroxynitrite yielding a stable spin adduct which is detectable by
      means of electron paramagnetic resonance (EPR) spectroscopy in frozen tissues. In
      old rats RONS generation was significantly increased compared to their young
      counterparts in the following order: blood<skeletal muscle<lung<heart, but did
      not change in intestine, brain, liver, and kidney. Experiments with isolated
      heart mitochondria showed a significant rate of RONS generation in succinate
      supplemented mitochondria from old rats while no RONS were detected in
      mitochondria from young rats. This study identifies heart, lung, and skeletal
      muscle as the tissues with increased RONS formation as a function of age.

PMID- 15949707
TI  - Comparison of the properties of rare variants of alpha1-proteinase inhibitor
      expressed in COS-1 cells and assessment of their potential as risk factors in
      human disease.
AB  - Among the more than 75 known variants of alpha(1)-proteinase inhibitor, a sub
      population of rare, point mutations causing single amino acid replacements have
      been identified and classified as "at risk" alleles for development of pulmonary
      disease. In most cases, it is not clear how the amino acid replacements typical
      of these variants change the properties of the inhibitor to increase risk of
      disease in the affected individuals. To begin to address this question, we
      mutagenized a wild type alpha(1)-proteinase inhibitor cDNA to encode a panel of
      eight different point mutants reported to be associated with increased risk for
      development of pulmonary disease. These variants were then expressed in COS-l
      cells transiently transfected with plasmids containing the altered cDNAs. The
      effects of the mutations on the rates of secretion, cellular location,
      intracellular degradation, activity, stability, and tendency to aggregate were
      determined. Results of these studies show that, in some cases, the mutations
      affect the rate of secretion, the activity or both of these properties of
      alpha(1)-proteinase inhibitor in a manner consistent with its designation as an
      "at-risk" allele. In other cases, the mutations do not significantly change the
      properties of the inhibitor, suggesting that these may be normal variants and
      that their expression may not increase the risk of disease.

PMID- 15949708
TI  - Characterization of the first described mutation of human red blood cell
      phosphoglycerate mutase.
AB  - In a patient with clinical diagnosis of Hereditary Spherocytosis and partial
      deficiency (50%) of red blood cell phosphoglycerate mutase (PGAM) activity, we
      have recently reported [A. Repiso, P. Perez de la Ossa, X. Aviles, B. Oliva, J.
      Junca, R. Oliva, E. Garcia, J.L.L. Vives-Corrons, J. Carreras, F. Climent, Red
      blood cell phosphoglycerate mutase. Description of the first human BB isoenzyme
      mutation, Haematologica 88 (2003) (03) ECR07] the first described mutation of
      type B PGAM subunit that as a dimer constitutes the PGAM (EC 5.4.2.1) isoenzyme
      present in red blood cells. The mutation is the substitution c.690G>A
      (p.Met230Ile). In this report, we show that the mutated PGAM possesses an
      abnormal behaviour on ion-exchange chromatography and is more thermo-labile that
      the native enzyme. We also confirm that, similar to the PGAM isoenzymes from
      other sources, the BB-PGAM from human erythrocytes has a ping pong or
      phosphoenzyme mechanism, and that the mutation does not significantly change the
      K(m) and K(i) values, and the optimum pH of the enzyme. The increased instability
      of the mutated enzyme can account for the decreased PGAM activity in patient's
      red blood cells. However, the implication of a change of the k(cat) produced by
      the mutation cannot be discarded, since we could not determine the k(cat) value
      of the mutated PGAM.

PMID- 15949709
TI  - The protective effect of alpha-crystallin against acute inflammation in mice.
AB  - Acute inflammation can activate macrophages or monocytes and subsequently release
      several inflammatory cytokines and reactive oxygen species (ROS). Oxidative
      stress triggered by the production of ROS plays deleterious role leading to
      multiple organ failure. This study was designed to investigate the prophylactic
      effect of alpha-crystallin, a major chaperone lens protein comprising of alpha-A
      and alpha-B subunits in inflammation-induced mice. Mice were divided into three
      groups (n=6 in each): control, inflammation and alpha-crystallin-treated. Results
      show that ROS was significantly higher in the lymphocytes, hepatocytes and
      astrocytes (P<0.05) of inflammation-induced mice when compared to control, but no
      significant changes were observed in the alpha-crystallin-treated group.
      Increased level of lipid peroxidation (LPO) and decreased activities of
      antioxidant such as superoxide dismutase (SOD), catalase, glutathione peroxidase
      and glutathione were observed in the inflammation-induced mice when compared to
      control, whereas the activities of these were found to be normal followed by
      alpha-crystallin treatment. We also observed a reduction in reduced glutathione
      levels in hepatocytes of inflammation-induced mice, which were normalized on
      alpha-crystallin treatment. The in vitro study has shown that alpha-crystallin
      treatment not only suppresses the increase in LPO levels but also inhibits the
      lipid breakdown resulting from autooxidation in mouse cerebral cortex homogenate,
      and strongly suggests that alpha-crystallin therapy may serve as a potent
      pharmacological agent in systemic inflammation.

PMID- 15949710
TI  - Enzymes that hydrolyze adenine nucleotides in platelets from breast cancer
      patients.
AB  - The activities of NTPDase (EC 3.6.1.5, apyrase, CD39) and 5'-nucleotidase (EC
      3.1.3.5, CD73) enzymes were analyzed in platelets from breast cancer patients.
      Initially, patients were compared in terms of length (years) of tamoxifen use.
      The following groups were studied: breast cancer patients who did not use
      tamoxifen, patients using tamoxifen for 1-48 months, patients using tamoxifen for
      49-84 months, and controls (healthy subjects). Results demonstrated that
      adenosine triphosphate (ATP) hydrolysis was enhanced (F(3,114)=8.53; P<0.001) and
      adenosine diphosphate (ADP) hydrolysis was reduced (F(3,106)=5.09, P=0.002) as a
      function of tamoxifen use, while adenosine monophosphate (AMP) hydrolysis was
      unchanged. Next, patients were compared statistically according to disease stage,
      determined by the tumor-node-metastasis (TNM) staging system for classifying
      breast tumor. ATP hydrolysis was significantly elevated in patients with stage I
      and II breast cancer (F(4,113)=4.35; P=0.003), but was normal in patients with
      stage III and IV cancer. ADP hydrolysis was reduced in stages II to IV
      (F(4,105)=3.88, P=0.006) and AMP hydrolysis was elevated in stage II
      (F(4,105)=3.45 P=0.01), but was normal in stages III and IV. Platelet aggregation
      time was similar in all patients regardless of tamoxifen use or disease stage.
      Prothrombin time (PT) and activated partial thromboplastin time (APTT) were also
      within the normal range and similar among all groups. Similarly, fibrinogen and
      fibrin degradation product (FDP) were unchanged in all groups. In conclusion, our
      study demonstrated for the first time that hydrolysis of adenine nucleotides is
      modified in platelets from breast cancer patients taking tamoxifen.

PMID- 15949711
TI  - Transgenic mice overexpressing SREBP-1a under the control of the PEPCK promoter
      exhibit insulin resistance, but not diabetes.
AB  - Sterol regulatory element-binding protein-1 (SREBP-1) is a transcription factor
      which regulates genes involved in the synthesis of fatty acids and triglycerides.
      The overexpression of nuclear SREBP-1a in transgenic mice under the control of
      the PEPCK promoter (TgSREBP-1a) caused a massively enlarged fatty liver and
      disappearance of peripheral white adipose tissue. In the current study, we
      estimated the impact of this lipid transcription factor on plasma glucose/insulin
      metabolism in vivo. TgSREBP-1a exhibited mild peripheral insulin resistance as
      evidenced by hyperinsulinemia both at fasting and after intravenous glucose
      loading, and retarded glucose reduction after insulin injection due to decreased
      plasma leptin levels. Intriguingly, hyperinsulinemia in TgSREBP-1a mice was
      markedly exacerbated in a fed state and sustained after intravenous glucose
      loading, and paradoxically decreased after the portal injection of glucose.
      TgSREBP-1a mice consistently showed very small plasma glucose increases after
      portal glucose loading because of a large capacity for hepatic glucose uptake.
      These data suggested that hepatic insulin resistance emerges postprandially. In
      addition, pancreatic islets from TgSREBP-1a were enlarged. These data demonstrate
      that SREBP-1a activation in the liver has a strong impact on plasma insulin
      levels, implicating the potential role of SREBPs in hepatic insulin metabolism
      relating to insulin resistance.

PMID- 15949712
TI  - Magnetic characterisation of rat muscle tissues after subcutaneous iron dextran
      injection.
AB  - Ex vivo freeze-dried rat muscle tissues, collected at different times t after a
      single dose of subcutaneously injected iron dextran, have been magnetically
      characterised. The AC susceptibility of the tissues shows an overall
      superparamagnetic behaviour and the dependence on t of, especially, the out-of
      phase component is remarkably systematic despite the fact that each tissue
      originates in a different rat individual. The experiments show that the
      akaganeite (beta-FeOOH) nanoparticles contained in the injected drug are
      progressively degraded in the living tissue and, at times of the order of 1 month
      and for all the analysed rat individuals, converge to a magnetically well-defined
      species with much narrower magnetic activation energy distribution than iron
      dextran. Thorough transmission electron microscopy experiments of the same
      tissues indicate the presence of oxyhydroxide particles, whose size decreases for
      increasing t in agreement with the interpretation of the magnetic susceptibility.
      The conclusions drawn from the magnetic study do well correspond to the
      properties of the whole tissue since no biochemical extraction work has been
      done. The AC susceptibility appears to be a valuable and complementary tool in
      pharmacological studies of iron-containing drugs.

PMID- 15949713
TI  - Gut-derived norepinephrine plays an important role in up-regulating IL-1beta and
      IL-10.
AB  - Previous studies have shown that the gut is a major source of norepinephrine (NE)
      released in early sepsis and that gut-derived NE plays an important role in up
      regulating TNF-alpha expression in Kupffer cells (KC) via an alpha(2)
      adrenoceptor (alpha(2)-AR) pathway. However, it remains unknown whether NE
      affects the release of other inflammatory cytokines such as IL-1beta and IL-10
      and, if so, whether alpha(2)-AR is also involved in such a process. To study
      this, a branch of the portal vein in normal adult male rats was cannulated under
      anesthesia. NE (20 muM in ascorbate saline), NE plus yohimbine (YHB, a specific
      alpha(2)-AR antagonist, 1 mM) or vehicle (0.1% ascorbate saline) was infused at a
      rate of 13 mul/min for 2 h. The above rate of NE infusion was used to increase
      the portal level of NE to approximately 20 nM, similar to that observed in
      sepsis. Blood samples were then collected and serum levels of IL-1beta and IL-10
      were measured. In addition, the KC was isolated from normal rats and stimulated
      with either NE (20 nM) or NE plus YHB (1 muM). The gene expression of IL-1beta
      and IL-10 in KC and their supernatant levels were assessed. The results indicate
      that serum levels of IL-1beta and IL-10 increased significantly after the
      intraportal infusion of NE. Co-administration of NE and YHB, however,
      significantly attenuated IL-1beta and IL-10 production. Similarly, IL-1beta and
      IL-10 gene expression and release from KC were up-regulated by NE stimulation,
      whereas YHB attenuated both cytokines. Thus, gut-derived NE up-regulates IL-1beta
      and IL-10 expression and release in the liver through an alpha(2)-AR pathway.
      Since adenylate cyclase activator forskolin prevents the increase in NE-induced
      IL-1beta and IL-10, the up-regulatory effect of NE on those cytokines appears to
      be mediated, at least in part, by inhibition of adenylate cyclase and reduction
      in intracellular cyclic AMP levels.

PMID- 15949714
TI  - The presence of leukocyte CC-chemokine receptor 2 in CCR2 knockout mice promotes
      atherogenesis.
AB  - OBJECTIVE: To selectively determine the role of leukocyte CC-chemokine receptor 2
      (CCR2) in atherogenesis. METHODS AND RESULTS: Bone marrow progenitor cells
      harvested from CCR2(+/+) mice were transplanted into irradiated CCR2(-/-) mice,
      representing the whole-body absence of CCR2 except in leukocytes. Transplantation
      of CCR2(-/-) bone marrow into CCR2(-/-) mice served as control. Eight weeks after
      bone marrow transplantation, the diet of regular chow was switched to a high
      cholesterol diet for another 10 weeks in order to induce atherosclerosis. No
      significant differences in serum cholesterol and triglyceride levels were
      observed between the two groups. However, the mean cross-sectional aortic root
      lesion area of CCR2(+/+)-->CCR2(-/-) mice amounted up to 12.28+/-3.28x10(4)
      microm(2), compared with only 3.08+/-0.74 x 10(4) microm(2) observed in the CCR2(
      /-)-->CCR2(-/-) group. Thus, the presence of CCR2 exclusively on leukocytes
      induces a fourfold increase in aortic lesion area. This extent of lesion
      development was comparable to C57Bl/6 mice receiving CCR2(+/+) bone marrow
      (10.08+/-3.30x10(4) microm(2)). CONCLUSION: These results point at a dominant
      role of leukocyte CCR2 in atherogenesis, implying that CCR2 from nonleukocyte
      sources, like endothelial cells or smooth muscle cells, is less critical in the
      initiation of atherosclerosis. Pharmacological inhibition of leukocyte CCR2
      function might be a promising strategy to prevent atherosclerosis.

PMID- 15949716
TI  - Glucose phosphate isomerase deficiency: enzymatic and familial characterization
      of Arg346His mutation.
AB  - Homozygous glucose phosphate isomerase (GPI) deficiency is one of the most
      important genetic disorders responsible for chronic non-spherocytic hemolytic
      anemia (CNSHA), a red blood cell autosomal recessive genetic disorder which
      causes severe metabolic alterations. In this work, we studied a patient with
      CNSHA due to an 82% loss of GPI activity resulting from the homozygous missense
      replacement in cDNA position 1040G>A, which leads to substitution of the protein
      residue A346H mutation. The enzyme is present in a dimeric form necessary for
      normal activity; the A346H mutation causes a loss of GPI capability to dimerize,
      which renders the enzyme more susceptible to thermolability and produces
      significant changes in erythrocyte metabolism.

PMID- 15949715
TI  - Propionic and methylmalonic acids increase cAMP levels in slices of cerebral
      cortex of young rats via adrenergic and glutamatergic mechanisms.
AB  - We have previously described that propionic (PA) and methylmalonic (MMA) acids
      increased the in vitro phosphorylation of cytoskeletal proteins through cAMP
      dependent protein kinase and glutamate. In the present study we investigated the
      in vitro effects of 1 mM glutamate, 2.5 mM MMA and 2.5 mM PA on cAMP levels in
      the slices of cerebral cortex of young rats. Results showed that PA, MMA and
      glutamate increased cAMP levels after 30 min of incubation, while the beta
      adrenergic agonist epinephrine elicited a similar effect only at a shorter
      incubation time. Then effects were prevented by the beta-adrenergic antagonist
      propranolol, rather than by glutamate antagonists (AP5, CNQX and MCPG),
      suggesting that they were mediated by beta-adrenergic receptors. In addition,
      glutamate antagonists per se induced increased cAMP levels; however propranolol
      prevented only the effect elicited by the metabotropic glutamate antagonist MCPG.
      Taken together, it is feasible that PA and MMA increase cAMP synthesis via a beta
      adrenergic/G protein coupled pathway, in a glutamate-dependent manner. Although
      additional studies will be necessary to evaluate the importance of these
      observations for the neuropathology of propionic and methylmalonic acidemias, it
      is possible that high brain cAMP levels may contribute to a certain extent to the
      neurological dysfunction of the affected individuals.

PMID- 15949717
TI  - Effect of quinones on microtubule polymerization: a link between oxidative stress
      and cytoskeletal alterations in Alzheimer's disease.
AB  - Increases in the concentration of quinones, such as benzoquinone, in pathological
      processes mediated by oxidative imbalance play a role in the disorganization and
      disassembly of the microtubule network in both non-neural and neural cells. In
      this study, we show that the effects on microtubules appear to be a direct result
      of the action of the quinones on tubulin, the main component of microtubules,
      since tubulin modification by quinones, including benzoquinone and juglone, leads
      to aggregation into dimers and other oligomers. Therefore, quinones and quinone
      mediated effects provide a mechanistic link between oxidative stress, microtubule
      disruption, neuronal dysfunction and death, i.e., key salient feature of
      Alzheimer's disease.

PMID- 15949718
TI  - Calcium ionophore A23187 action on cardiac myocytes is accompanied by enhanced
      production of reactive oxygen species.
AB  - We show that rat neonatal cardiac myocytes exposed to 1 micromol/l of the calcium
      ionophore A23187 respond with an enhanced production of reactive oxygen species
      (ROS). This dose is not cytotoxic to the myocytes. A higher concentration (10
      micromol/l) evokes less ROS production and is significantly cytotoxic 24 h after
      exposure, but not immediately after removal of the A23187, when ROS are measured.
      Both cell death and the decrease in mitochondrial potential are only partially
      sensitive to MPT inhibitor cyclosporin A. Experiments performed to elucidate the
      sources of ROS included use of the nitric oxide synthase (NOS) inhibitor L-NAME;
      NOS involvement was excluded. Experiments with the oxidative phosphorylation
      uncoupler CCCP revealed that mitochondria are at least partially responsible for
      the observed effect. Further studies with cyclooxygenase (COX) and lipoxygenase
      (LOX) inhibitors (indomethacin and MK886, respectively) showed that these enzymes
      could also be sources of ROS when the calcium level is elevated. Their effect
      appeared to be independent of phospholipase A(2) inhibition, suggesting that COX
      and LOX stimulation is not due to elevated substrate (arachidonic acid)
      concentration but rather to a direct effect of calcium.

PMID- 15949719
TI  - Towards a model to explain the intragenic complementation in the heteromultimeric
      protein propionyl-CoA carboxylase.
AB  - Mutations in the PCCA or PCCB genes coding for alpha and beta subunits of
      propionyl CoA carboxylase can cause propionic acidemia. To understand the
      molecular basis of the intragenic complementation previously reported at the PCCB
      locus, we now examine the complementation behaviour of four carboxy-terminal and
      11 amino-terminal naturally occurring mutant alleles both using cell fusion and
      reconstructing the complementation event by transfecting the mutant cDNAs to
      generate multimeric hybrid proteins. Alleles carrying mutations p.R410W and
      p.W531X are able to complement with 10 out of 11 amino-terminal mutations
      assayed. Only the unstable p.R512C, p.L519P and p.G112D mutants fail to
      complement. The results analyzed in the framework of the crystal structure of the
      homologous 12S transcarboxylase from Propionibacterium shermanii show that all
      mutant alleles studied are located at beta subunits interfaces, complementing
      alleles at the inter-trimer interface, where the catalysis probably happens, and
      non-complementing alleles at the intra-trimer interface, probably disrupting the
      trimer formation. Our results also show a remarkable stabilization effect when
      p.R410W is cotransfected with p.G246V. We propose a model for intragenic
      complementation requiring the production of two different beta subunits carrying
      carboxy and amino-terminal mutations that allow regenerating functional active
      sites and in which a stabilization effect between subunits could be relevant to
      ameliorate the biochemical phenotype of each mutation separately.

PMID- 15949720
TI  - Progressive left ventricular remodeling, myocyte apoptosis, and protein signaling
      cascades after myocardial infarction in rabbits.
AB  - To determine the temporal changes in oxidative stress, mitogen-activated protein
      (MAP) kinases and mitochondrial apoptotic proteins, and their relationship to
      myocyte apoptosis in the remote noninfarcted myocardium after myocardial
      infarction (MI), rabbits were randomly assigned to either coronary artery
      ligation to produce MI or sham operation. The animals were sacrificed at 1, 4, 8,
      or 12 weeks after coronary artery occlusion. Sham rabbits were sacrificed at 12
      weeks after surgery. MI rabbits exhibited progressive increases of left
      ventricular (LV) end-diastolic pressure and end-diastolic dimension, and
      progressive decreases of LV fractional shortening and dP/dt over 12 weeks. The LV
      remodeling with LV chamber dilation and LV systolic dysfunction was temporally
      associated with progressive increases of cardiac oxidative stress as evidenced by
      decreased myocardial reduced-to-oxidized-glutathione ratio and increased
      myocardial 8-hydroxydeoxyguanosine and myocyte apoptosis. The ERK and JNK
      activities were decreased while p38 MAP kinase activity was increased with age of
      MI. The extent of p38 MAP kinase activation correlated with Bcl-2
      phosphorylation. Bcl-2 protein was decreased in both mitochondrial and cytosolic
      fractions with age of MI. Bax protein was increased in both mitochondrial and
      cytosolic fractions. Cytochrome c was reduced in mitochondrial fraction and
      increased in cytosolic fraction in a time-dependent manner after MI. Cleaved
      caspase 9 and caspase 3 proteins were time-dependently increased after MI. These
      data suggest that p38 MAP kinase activation is not only time-dependent after MI,
      but also correlates with oxidative stress, Bcl-2 phosphorylation, and myocyte
      apoptosis. These changes in the remote noninfarcted myocardium may contribute to
      LV remodeling and dysfunction after MI.

PMID- 15949721
TI  - Influence of UV-B exclusion and selenium treatment on photochemical efficiency of
      photosystem II, yield and respiratory potential in pumpkins (Cucurbita pepo L.).
AB  - The influence of ambient and filtered solar ultraviolet-B (UV)-B radiation and of
      selenium treatment was determined on photochemical efficiency, respiratory
      potential measured by electron transport system (ETS) activity, and yield in
      pumpkins, Cucurbita pepo L. Yield and ETS activity were higher when solar UV-B
      was filtered out. The results suggested that the decreased yield was related to
      the UV-B impaired flow of electrons in the respiratory chain. Selenium increased
      yield under ambient radiation conditions. However, no significant effect of
      excluding UV-B radiation or of treatment with selenium was observed on the
      photochemical efficiency of photosystem II (PSII).

PMID- 15949722
TI  - The impact and outcome of transplant coronary artery disease in a pediatric
      population: a 9-year multi-institutional study.
AB  - BACKGROUND: Transplant coronary artery disease (TCAD) limits survival in heart
      transplant recipients; however, its incidence in children is unknown. The purpose
      of this study was to determine the angiographic incidence of TCAD, potential risk
      factors, and outcomes in a large pediatric cohort. METHODS: From January 1993 to
      December 1, a total of 1,222 children, aged newborn to 17 years, underwent
      primary cardiac transplantation at 20 institutions. A total of 2,049 coronary
      angiograms were performed in 751 patients. All angiograms were graded for
      coronary disease and results were submitted to the Pediatric Heart Transplant
      Study database. We analyzed time-related freedom from graded severity and events
      from coronary disease, and we examined risk factors. RESULTS: The incidence of
      angiographic abnormalities at 1, 3, and 5 years was 2%, 9%, and 17%,
      respectively; however, moderate-to-severe disease occurred in only 6% at 5 years,
      compared with 15% in the adult transplant database (p <0.0001). The major risk
      factors were older recipient and donor age. Two or more episodes of rejection in
      the 1st year correlated with coronary disease (p = 0.05). Overall freedom from
      graft loss caused by primary TCAD was 99%, 96%, and 91% at 1, 5, and 9 years
      after heart transplantation, respectively. Death or graft loss occurred within 2
      years of diagnosis in patients with severe disease; 24% of patients with any
      coronary disease died within 2 years. CONCLUSIONS: The incidence of TCAD in
      children is smaller than the incidence in adults, but increases with age. Graft
      loss is infrequent in children; however, severe coronary disease correlates with
      poor prognosis.

PMID- 15949723
TI  - Reliability for grading acute rejection and airway inflammation after lung
      transplantation.
AB  - BACKGROUND: The Lung Rejection Study Group (LRSG) created a scheme for grading
      acute allograft rejection in 1990 and then revised it in 1996, but virtually no
      studies have evaluated the reliability of this formulation. This investigation
      assessed the reliability of the current LRSG system by determining inter- and
      intrareader agreement for grading transbronchial biopsy samples from lung
      transplant recipients. METHODS: Biopsy samples from a cohort of 204 recipients
      were reviewed and classified by a single pathologist who was blinded to original
      interpretations. The "A" and "B" rejection grades from this contemporary review
      were compared with original grades by the kappa statistic. RESULTS: For "A"
      grading, weighted kappa was 0.65 (95% confidence interval [CI] 0.60-0.70) for
      interreader agreement (n = 529 specimens) and 0.65 (95% CI 0.53-0.76) for
      intrareader agreement (n = 97 specimens). For "B" grading, weighted kappa was
      0.26 (95% CI 0.14-0.39) for interreader agreement (n = 164 specimens) and 0.33
      (95% CI 0.15-0.51) for intrareader agreement (n = 58 specimens). CONCLUSIONS: On
      the basis of the analysis of the LRSG scheme, "A" grades exhibit very good
      reliability, but "B" grades have only fair reliability, and steps to improve this
      shortcoming should be taken.

PMID- 15949724
TI  - Interferon-gamma knockout fails to confer protection against obliteration in
      heterotopic murine tracheal allografts.
AB  - BACKGROUND: Interferon-gamma, produced by T-helper cells, activates macrophages
      and increases expression of major histocompatibility complex (MHC) products in
      acute and chronic rejection. We investigated the role of interferon-gamma in
      murine heterotopic tracheal allografts. METHODS: Tracheas from BALB/c mice were
      heterotopically transplanted to BALB/c (12 isografts: 2 weeks [n = 6] and 4 weeks
      [n = 6], C57BL/6 (12 allografts: 2 weeks [n = 6] and 4 weeks [n = 6]) and C57BL/6
      interferon-gamma knockout mice (12 interferon-gamma knockout allografts: 2 weeks
      [n = 4] and 4 weeks [n = 8]). BALB/c interferon-gamma knockout tracheas were
      transplanted to C57BL/6 mice (reverse knockout: 4 weeks [n = 6]) and BALB/c
      interferon-gamma knockout mice (4 weeks [n = 2]). C57BL/6 tracheas were
      transplanted to Bm12 mice (MHC Class II mismatch allografts: 4 weeks [n = 6]).
      Conventional histology and immunohistochemistry for CD4, CD8 and CD11b were
      performed. RESULTS: Minimal (<20%) obliteration was seen at 2 weeks in the
      allograft groups. No obliteration was seen in the isograft groups. However, all
      allografts were completely obliterated at 4 weeks. Interferon-gamma knockout
      allograft combinations displayed severe rejection characterized by intense intra-
      and extraluminal infiltration by CD4-, CD8- and CD11b-labeled cells. The MHC
      Class II mismatch allograft group showed normal epithelium and mild sub
      epithelial infiltration by CD4+ cells at 4 weeks (CD8-, CD11b-). CONCLUSIONS:
      Absence of interferon-gamma does not protect the allograft from obliteration.
      Epithelial destruction by cytotoxic T cells appears to be an important mechanism
      in the development of obliteration in murine heterotopic tracheal allografts.

PMID- 15949725
TI  - Blunted vascular response to endothelin-a receptor blockade in cyclosporine
      treated lung transplant recipients.
AB  - BACKGROUND: The majority of cyclosporine-treated transplant recipients develop
      hypertension. Endothelin-1 (ET-1) has been suggested to mediate cyclosporine
      induced vasoconstriction when binding to ET-A receptors. We hypothesized that
      cyclosporine-treated lung transplant recipients have an increased basal vascular
      resistance and an augmented response to ET-A receptor blockade. METHODS: The
      selective ET-A receptor blocker BQ-123 (10 and 50 nmol/min) was infused into the
      brachial artery, alone or in combination with the nitric oxide synthase inhibitor
      NG-monomethyl-L-arginine acetate (L-NMMA) (2 and 4 micromol/min) in 10 lung
      transplant recipients without pharmacologically treated hypertension and 8
      healthy controls. Forearm blood flow (FBF) was measured by venous occlusion
      plethysmography and plasma levels of ET-1 were analyzed. RESULTS: Baseline
      forearm vascular resistance did not differ between recipients and controls (32 +/
      4 vs 42 +/- 7 mmHg/ml/min, p = 0.32). BQ-123 increased FBF in controls but not
      in recipients (26% +/- 9% vs 5% +/- 11% at 10 nmol/min, p = 0.043 between
      groups). Coinfusion of BQ-123 and L-NMMA caused a comparable decrease in FBF in
      recipients and controls (-26% +/- 11%, vs -34% +/- 7%). Baseline ET-1 was higher
      in recipients (17.2 +/- 1.1 vs 14.7 +/- 0.8 pg/ml, p = 0.038). BQ-123 infusion
      increased plasma ET-1 in controls but not in recipients (+24% +/- 11% vs -0.4% +/
      6.2%, p = 0.029 between groups). CONCLUSIONS: The results demonstrate that
      cyclosporine-treated lung transplant recipients have increased plasma levels of
      ET-1 and a blunted response to ET-A receptor blockade compared with healthy
      subjects. In contrast, we found no evidence for an increased basal vascular
      resistance in transplant recipients. These alterations in endothelin handling may
      contribute to the development of transplant-associated hypertension.

PMID- 15949726
TI  - Lung retransplantation after posttransplantation lymphoproliferative disorder
      (PTLD): a single-center experience and review of literature of PTLD in lung
      transplant recipients.
AB  - BACKGROUND: Retransplantation in adult lung transplant recipients developing
      progressive bronchiolitis obliterans syndrome as a consequence of
      posttransplantation lymphoproliferative disorder (PTLD) therapy has not been
      reported in the literature. Literature on PTLD after lung transplantation is
      limited mostly to case reports or small case series, limiting the validity of
      conclusions. METHODS: Retrospective chart review of patients at our center.
      Analysis of pooled data published on lung transplant patients developing PTLD.
      RESULTS: Two patients who underwent pulmonary retransplants for PTLD have
      functioning grafts 23 and 36 months postoperatively, with no evidence of PTLD
      recurrence. Review and analysis of published data and from our center revealed
      that incidence of PTLD, proportion of patients with thoracic involvement, and
      proportion of patients who were Epstein-Barr virus seronegative before
      transplantation decreased continuously as a function of time from transplant.
      Patients developing PTLD within the first 6 months after transplantation had a
      clinically distinct pattern of PTLD and a significantly better survival than
      patients developing PTLD more than 6 months after lung transplant. CONCLUSIONS:
      Lung retransplantation can be considered after careful selection for lung
      transplant recipients developing bronchiolitis obliterans syndrome as a
      consequence of reduced immunosuppression for PTLD. Acquisition of PTLD and
      pattern of organ involvement is a continuous process as a function of time.
      Defining "early PTLD" as occurring in the first 6 months more accurately predicts
      progress and prognosis of this disease than the traditional 1 year definition of
      early vs late onset PTLD.

PMID- 15949727
TI  - Projected survival benefit as criterion for listing and organ allocation in heart
      transplantation.
AB  - BACKGROUND: Current policies for the selection of candidates and the allocation
      of hearts for transplantation give priority to patients at greatest risk if not
      transplanted. However, to achieve best use of the donated organs, it is necessary
      to estimate the net benefit associated with transplantation. METHODS: The
      survival benefit associated with being listed or not, with being transplanted or
      left on the waiting list, or with being transplanted or being denied the
      opportunity for a transplant can be estimated by means of time-to-event modeling
      of competing risks with intervening states. The data were obtained from the Organ
      Procurement and Transplantation Network and describe the outcomes of listings
      from 1997 to June 1999. Our analyses assessed 9,059 heart transplantation
      candidates, who were followed for at least 1 and up to 2 years after listing.
      RESULTS: The probability of receiving a heart transplant does not increase with
      the probability of death while awaiting the transplant. It is comparable in the
      second and tenth deciles of risk (measured by the probability of death while
      awaiting a transplant) at 1 month after listing (15% vs 18%), but is considerably
      higher in the second decile at 6 months (53% vs 38%) and increasingly more so
      thereafter. The estimate of survival benefit stabilizes within 1 year of follow
      up. Through the fourth decile of risk, the benefit of being placed on the waiting
      list is negligible at best, but becomes substantial (10%) for patients in the
      highest 2 deciles. Heart transplantation may reduce survival in the least ill
      patients but is clearly strongly beneficial for severely ill patients, offering
      reductions of 20 to 35 percentage points in probability of death when compared
      with remaining on the waiting list or not receiving a transplant at all.
      CONCLUSIONS: Our analyses indicate that criteria other than severity of illness
      as measured by the probability of death are, in practice, dominant in the
      allocation of donated hearts for transplantation. High percentages of patients
      listed as well as those transplanted are not expected to undergo a substantial
      increase in probability of survival, and some are likely to be harmed. A survival
      benefit is anticipated only for severely ill patients. Estimation of the
      projected survival benefit of listing and of transplantation is feasible and may
      be used to prioritize patients and lead to the best use of donated organs.

PMID- 15949728
TI  - Nitric oxide versus prostaglandin E1 for reduction of pulmonary hypertension in
      heart transplant candidates.
AB  - BACKGROUND: We sought to directly compare the effects of prostaglandin E1 (PGE1)
      and nitric oxide (NO) in testing for pulmonary hypertension reversibility in
      heart transplant candidates. METHODS: We included 19 heart transplant candidates
      who fulfilled at least 1 of 3 criteria: pulmonary vascular resistance (PVR) of >4
      Wood units; transpulmonary gradient (TPG) of >12 mmHg; or systolic pulmonary
      artery pressure (PAP) of >60 mmHg. Patients randomly received either PGE1 (0.05,
      0.2 and 0.5 microg/kg/min) or NO (40, 60 and 80 ppm) and were crossed-over to the
      second medication after receiving the maximal dose of the first. RESULTS: With
      PGE1, TPG decreased by 21% (baseline 20.3 +/- 6.8 mmHg; final 16.0 +/- 7.0 mmHg)
      compared to a 34% decrease with NO (baseline 20.8 +/- 6.2 mmHg; final 13.8 +/-
      5.4 mmHg) (p = 0.13). PVR decreased by 42% with PGE1 (baseline 6.2 +/- 4.0 Wood
      units; final 3.6 +/- 1.8 Wood units) and by 47% with NO (baseline 6.0 +/- 3.9
      Wood units; final 3.2 +/- 1.6 Wood units) (p = 0.87). Mean systemic pressure
      decreased with PGE1 (baseline 76.1 +/- 10.5 mmHg; final 69.4 +/- 12.2 mmHg; -9%)
      but not with NO administration (baseline 70.2 +/- 14.7 mmHg; final 71.6 +/- 10.9
      mmHg; +2%) (p = 0.01). TPG was lowered to <12 mmHg in 14 patients. Of these, 6
      (46%) responded to both PGE1 and NO, 4 (27%) responded only to PGE1, and 4 (27%)
      responded only to NO. CONCLUSIONS: The effects of PGE1 and NO on pulmonary
      hypertension are comparable, with PGE1 having more systemic hypotensive effects.
      Due to variability of patient responses, we recommend multiple rather than single
      agent pharmacologic testing for the reversibility of pulmonary hypertension.

PMID- 15949729
TI  - Osteoporosis in adult survivors of adolescent cardiac transplantation may be
      related to hyperparathyroidism, mild renal insufficiency, and increased bone
      turnover.
AB  - BACKGROUND: Osteoporosis is common in adults who undergo cardiac transplantation.
      We hypothesized that adolescent cardiac transplant recipients also develop
      osteoporosis, which would persist into adulthood. METHODS: We evaluated 9 adult
      survivors of adolescent cardiac transplantation, aged 21-32, in a cross
      sectional, case-control study comparing bone mineral density, indices of mineral
      metabolism, and bone turnover markers. RESULTS: Osteoporosis (Z score < or = 
      2.0) was present in 56% of transplant recipients at the lumbar spine, 33% at the
      femoral neck, and 100% at the one-third radius. Subjects had mean bone mineral
      density Z scores of -2.3 +/- 0.9 at the spine, -1.6 +/- 0.7 at the femoral neck,
      and -3.2 +/- 0.7 at the one-third radius, significantly lower than controls at
      all sites (p < 0.001). Serum creatinine and vitamin D metabolites were normal and
      did not differ between subjects and controls. Serum calcium was lower, blood urea
      nitrogen was elevated, and creatinine clearance tended to be lower in transplant
      recipients. Parathyroid hormone (PTH) levels were 3-fold higher in subjects than
      controls, and 75% of subjects had elevated PTH levels. Markers of bone turnover
      were significantly higher in subjects than controls. CONCLUSIONS: Adult survivors
      of adolescent cardiac transplantation have mild renal insufficiency, secondary
      hyperparathyroidism, and biochemical evidence of increased bone turnover.
      Osteoporosis is common in these patients, particularly at the one-third radius, a
      site sensitive to the catabolic effects of sustained excessive PTH secretion. We
      conclude that adult survivors of adolescent cardiac transplantation should be
      evaluated for hyperparathyroidism and osteoporosis.

PMID- 15949730
TI  - Is bridging to transplantation with a left ventricular assist device a risk
      factor for transplant coronary artery disease?
AB  - BACKGROUND: Left ventricular assist device (LVAD) support is associated with
      coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA
      antibody production. Increased anti-HLA antibody production is associated with
      early transplant rejection, transplant coronary artery disease (CAD), and
      decreased post-transplant survival rates. We asked whether bridging to
      transplantation with an LVAD increases the risk of transplant CAD. METHODS: We
      reviewed data for all adults (>18 years old) who underwent heart transplantation
      at our institution between 1988 and 2000. After exclusion of transplant
      recipients who survived <3 years, we divided the remaining cohort into 2 groups:
      those bridged to transplantation with LVADs (mean duration of support, 149 +/-
      107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged
      to transplantation without LVADs (controls, n = 86). We compared groups in terms
      of disease cause, age, sex, donor age, panel-reactive antibody testing,
      crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of
      diabetes mellitus or treated hypertension, infections, calcium channel blocker
      use, transplant rejection, ischemic time, cytomegalovirus infection, pre
      transplant transfusion, and incidence of transplant CAD (defined as any coronary
      lesion identified by coronary angiography). We considered p < 0.05 to be
      significant. RESULTS: The bridged and control groups were similar in all respects
      except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007),
      post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl,
      p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001).
      The incidence of transplant CAD was similar in both groups during a 3-year follow
      up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p =
      0.969). Multivariate logistic regression analysis identified cholesterol
      concentration at 1 year after transplantation as a significant predictor of CAD
      at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984).
      CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk
      of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize
      potential risk factors for transplant CAD, such as increased cholesterol
      concentration, is warranted in all transplant recipients.

PMID- 15949731
TI  - Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin
      (Sangstat).
AB  - BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should
      induce effective immunosuppression, with a low rate of rejection in the initial
      phase after heart transplantation. Induction therapy with ATG allows post
      operative renal recovery without the negative effects of highly nephrotoxic
      cyclosporine levels. An increased rate of infection is a common problem, however,
      and has been associated with "over-immunosuppression" early after
      transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG
      induction therapy could be performed without increasing the risk of graft loss by
      rejection and whether reductions in infection rates and costs are possible.
      METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction
      therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant
      recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub
      populations were screened daily using flow cytometry. If total lymphocytes were
      <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+)
      <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl
      (reference >300/microl), then no ATG was given. Further immunosuppression was
      continued with triple therapy consisting of methylprednisolone, azathioprine and
      cyclosporine. An historic group of heart transplant recipients given a full-dose
      ATG regimen for 8 days served as controls. These recipients were treated with ATG
      (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl.
      Additional immunosuppressive treatment did not differ. Patients in both groups
      received systemic antibiotics (Imipenem) peri-operatively. Results of routine
      endomyocardial biopsies and rates of infections were examined. RESULTS: Study
      group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group,
      mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05)
      for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the
      control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the
      study group compared with 13% in the control group. Rate of deep sternal
      infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate
      in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs
      1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were
      treated successfully with 1,000 mg of methylprednisolone intravenously for 3
      days. Both groups showed a similar 1-year survival rate (study 88%, control 89%).
      CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for
      individualized immunosuppression. It is not associated with an increased rate of
      rejection. Lower doses of immunosuppression help to minimize the rates of
      infection. In addition, cytolytic induction therapy combined with reduced ATG
      results in significant cost reduction.

PMID- 15949732
TI  - Effects of short-term inhaled nitric oxide on interleukin-8 release after single
      lung transplantation in pigs.
AB  - BACKGROUND: Lung transplantation has evolved to become an effective treatment for
      a variety of end-stage lung diseases. However, severe reperfusion injury is still
      a major cause for postoperative morbidity and mortality. Although lung
      reperfusion injury is complex and has not been fully comprehended yet, neutrophil
      infiltration and cytokine activation have been postulated to play a main role.
      Recent studies showed that nitric oxide (NO) therapy has salutary effects on lung
      chronic and acute pathologies because it inhibits interleukin-8 (IL-8) release,
      but no data have been found on its effects during organ harvest. The aim of this
      study was to assess whether low doses of inhaled NO pre-treatment at the time of
      harvesting improves allograft function during early reperfusion in a porcine
      model. METHODS: Twenty-two Landrace pigs were randomly assigned to NO-treated and
      control groups. In NO-treated pigs, NO at 20 ppm was administered 30 min before
      harvest. During the early allograft reperfusion period IL-8 content, dynamic and
      static compliance and gas exchange (Pa/FiO2 and PaO2) were measured in both
      control and NO-treated lungs. RESULTS: Pre-treatment with NO at the time of
      harvesting showed improvement of allograft function in terms of dynamic (92 +/-
      8% in NO vs 72 +/- 7% in the control group, p < .05) and static (83 +/- 8% in NO
      vs 63 +/- 7% in the control group, p < 0.05) compliance and gas exchange (PaO2:
      96 +/- 4% in NO vs 74 +/- 4.5% in the control group, p < 0.01; Pa/FiO2: 97 +/- 5%
      in NO vs 74 +/- 5% in the control group, p < 0.01) by diminishing IL-8 (66.5 +/-
      4.7 pg/ml in NO versus 208 +/- 43 pg/ml in the control group, p < 0.05) release
      in pigs. CONCLUSION: These results show for the first time that NO pre-treatment
      at the time of harvesting reduces allograft reperfusion injury in part due to its
      effects on IL-8 release.

PMID- 15949733
TI  - The efficacy of partial liquid ventilation in lung protection during hypotension
      and cardiac arrest: preliminary study of lung transplantation using non-heart
      beating donors.
AB  - BACKGROUND: Because of the shortage of suitable brain-dead donors, the use of non
      heart-beating donor lungs has been investigated experimentally. However, no
      effective lung protection method has been developed. In this study, we
      preliminarily investigated the protective effect of partial liquid ventilation
      (PLV) on a non-heart-beating rabbit lung. METHODS: We used 20 male rabbits (mean
      weight, 3.7 kg) and divided them into 3 groups: the conventional ventilation
      (control) group, the PLV without cooling group, and the PLV with cooling group.
      After initially measuring donor cardiopulmonary function, we maintained
      hypotension at <50 mm Hg for 1 hour followed by 2-hour cardiac arrest. During
      this time, we used either conventional ventilation or PLV with or without cooling
      (4 degrees C) for ventilation, and we evaluated the changes in arterial blood gas
      analysis, pulmonary resistance and elastance, tissue interleukin-8 (IL-8)
      concentration, and histologic damage. RESULTS: We found no significant difference
      in arterial oxygen concentration or in carbon dioxide tension among the 3 groups
      in the hypotensive phase. Pulmonary elastance increased after perfusion of
      preservation solution in the control group. However, we found no change in
      elastance in the PLV groups, which was less than that in the control group.
      Histologic evaluation after perfusion of preservation solution revealed that
      alveolar structure was damaged significantly less and cell infiltration was
      milder in the PLV groups than in the control group. Although IL-8 concentrations
      in the controls increased after cardiac arrest, IL-8 in the PLV groups remained
      at baseline concentrations during the study period. CONCLUSION: In this
      experimental model of hypotension and cardiac arrest, PLV suppresses lung injury
      when compared with gas-controlled ventilation.

PMID- 15949734
TI  - Formation of 4-hydroxy-2-nonenal protein adducts in the ischemic rat heart after
      transplantation.
AB  - BACKGROUND: Free radicals formed during ischemia and reperfusion can lead to
      lipid peroxidation (LPO) and the formation of 4-hydroxy-2-nonenal (4-HNE), one of
      the most toxic products of LPO. Using a heterotopic rat heart transplantation
      model we investigated endogenous 4-HNE formation as a response to cold storage of
      the transplant and warm blood reperfusion in the recipient. METHODS: Lewis rat
      hearts were subjected to 30, 240 or 480 minutes of 4 degrees C cold ischemia in
      Bretschneider cardioplegic solution without or with transplantation and 240
      minute reperfusion in F344 recipients. The amount of 4-HNE modified proteins was
      quantified in rat heart cryosections with an antibody recognizing cysteine-,
      histidine- and lysine-4-HNE Michael adducts and image analysis of immunostained
      tissue. RESULTS: We detected 4-HNE-modified proteins in ischemic rat hearts after
      transplantation and reperfusion. In hearts submitted to ischemia only, 4-HNE
      protein adducts comprised 0.7 +/- 0.3% (30 minutes), 0.7 +/- 0.4% (240 minutes)
      and 0.2 +/- 0.1% (480 minutes) (mean +/- SEM) of the tissue area. Transplantation
      and reperfusion in the recipient significantly increased the amount of protein
      adducts to 6.8 +/- 2.6% (p = 0.041), 5.2 +/- 1.4% (p = 0.009) and 5.7 +/- 0.9% (p
      = 0.002) in 30-, 240- and 480-minute ischemic hearts, respectively. CONCLUSIONS:
      Under the conditions applied in the present study, cold ischemia for >30 minutes
      did not significantly alter the amount of 4-HNE protein adducts. However, because
      after transplantation and reperfusion, 6% of heart tissue consisted of 4-HNE
      modified proteins, it can be assumed that this damage negatively affects long
      term survival of the transplant.

PMID- 15949735
TI  - Myocardial restoration with embryonic stem cell bioartificial tissue
      transplantation.
AB  - BACKGROUND: The optimal cell-matrix combination for robust and sustained
      myocardial restoration has not been identified. The present study utilizes
      embryonic stem cells as the substrate of bioartificial myocardial tissue and
      evaluates engraftment in, and functional recovery of, the recipient heart.
      METHODS: Collagen type I was populated with undifferentiated green fluorescent
      protein (GFP)-positive mouse embryonic stem cells. An intramural left ventricular
      pouch was fashioned after ligation of the left anterior descending artery in an
      athymic nude rat heterotopic heart transplant model. The bioartificial mixture
      (0.125 ml) was implanted in the infarcted area within the pouch. Echocardiography
      was performed to assess fractional shortening in: Group I, infarcted rats that
      received cell-matrix implants; Group II, rats given matrix implant without cells;
      Group III, rats given no matrix or cells; and Group IV, rats receiving
      transplanted hearts without ligation (n = 5/group). Hearts were stained for GFP,
      cardiac markers (connexin-43, alpha-sarcomeric actin), hematoxylin-eosin (H&E)
      and trichrome. RESULTS: Embryonic stem cells formed stable intramyocardial grafts
      that were incorporated into the surrounding area without distorting myocardial
      geometry, thereby preventing ventricular wall thinning (anterior wall thickness
      was: Group I, 1.4 +/- 0.1 mm; Group II, 1.0 +/- 0.1 mm, Group III, 0.9 +/- 0.2
      mm; and Group IV, 1.3 +/- 0.2 mm). The inoculated cells expressed connexin-43 and
      alpha-sarcomeric actin in vivo. Fractional shortening was better in embryonic
      stem cell-treated animals (Group I, 21.5 +/- 3.5%; Group II, 12.4 +/- 2.8%; Group
      III, 8.2 +/- 2.9%; Group IV, 23.2 +/- 4.2%). CONCLUSIONS: Embryonic stem cells
      are an efficient alternative substrate for myocardial tissue engineering and can
      prevent myocardial wall thinning and improve contractility after implantation
      into injured myocardium in a 3-dimensional matrix.

PMID- 15949736
TI  - Two simple echo-Doppler measurements can accurately identify pulmonary
      hypertension in the large majority of patients with chronic heart failure.
AB  - BACKGROUND: The assessment of pulmonary hypertension in patients with heart
      failure is of great clinical importance not only for diagnostic purposes but also
      for prognostication. The present study was undertaken on a consecutive basis with
      a group of patients with chronic heart failure. Patients were evaluated for their
      suitability for heart transplantation: (1) to explore the diagnostic accuracy of
      several echo Doppler parameters of pulmonary hemodynamics in predicting the
      presence of elevated pulmonary artery pressure (defined as pulmonary artery
      systolic pressure > or =35 mmHg and mean pulmonary artery pressure >20 mmHg); (2)
      to assess the diagnostic ability of the same parameters to identify patients with
      elevated pulmonary vascular resistance; and (3) to evaluate the influence of
      right ventricular function and degree of tricuspid regurgitation in modifying
      diagnostic accuracy. METHODS: Echo Doppler examination and right heart
      catheterization were performed consecutively within 24 hours in 86 patients. The
      optimal cut-off value for a series of echo Doppler parameters capable of
      identifying patients with pulmonary hypertension was obtained by dividing the
      entire sample into 2 groups; the optimal threshold (highest sensitivity and
      specificity) of the echo and Doppler parameters used to classify patients with
      and without pulmonary hypertension was determined in 67% of cases by means of the
      receiver operating characteristic (ROC) curve: this was the testing sample. The
      proportion of cases classified correctly according to the selected cut-off was
      computed. The remaining 33% of cases represented the validation sample:
      sensitivity, specificity and predictive values (and their 95% confidence
      intervals [CIs]) for identifying pulmonary hypertension were calculated from the
      proposed cut-offs in this second sample. Finally, the overall performance of the
      echo Doppler parameters was assessed over the whole sample by considering the
      extent of the area under the ROC curve (A-ROC) and its 95% CI, for the dichotomic
      measurement. RESULTS: On right heart catheterization, a pulmonary artery systolic
      (PAPs) pressure > or =35 mmHg plus a mean pressure (mean PAP) >20 mmHg was
      documented in 49 of 86 cases (57%), for whom mean values were 56 +/- 17 and 38 +/
      11 mmHg, respectively. The proportion of cases identified correctly as having
      pulmonary hypertension was highest for PAPs (88%) and mean PAP (85%) in addition
      to acceleration time of pulmonary artery systolic flow (ACT) (79%) and pulmonary
      artery diastolic pressure obtained utilizing the early phase of the tricuspid
      regurgitation spectral flow (PAPd/TR) (75%). PAPd/TR performed better in the
      validating sample in terms of diagnostic ability, with high sensitivity and
      specificity (100% and 60%) and positive and negative predictive values (PPV 80%,
      NPV 100%). PAPs, mean PAP, ACT and PAPd/TR confirmed their prevailing diagnostic
      ability (A-ROC from 0.74 to 0.86) in identifying pulmonary hypertension with fair
      to high feasibility (67% to 91%) and an odds ratio (OR) indicative of strong
      association. ACT and PAPd/TR, the 2 parameters with the highest feasibility,
      allowed us to identify 46 of 49 (94%) hypertensive cases. The same parameters did
      not perform well in identifying patients with increased vascular resistance, with
      A-ROC ranging from 0.55 to 0.69. Heterogeneity of effect, due to right
      ventricular function or tricuspid regurgitation degree, could not be demonstrated
      in the ability of the echo Doppler measurements to identify pulmonary
      hypertension. CONCLUSIONS: ACT, PAPd/TR, PAPs and mean PAP have been shown to
      accurately classify patients with chronic heart failure with or without pulmonary
      hypertension. In particular, ACT and PAPd/TR alone allowed reliable and accurate
      definition of pulmonary hypertension in 94% of patients, regardless of right
      ventricular function or degree of tricuspid regurgitation. Non-invasive pulmonary
      pressure assessment by the referred method might be useful in the evaluation of
      heart transplant candidates.

PMID- 15949737
TI  - Does lung transplantation improve health-related quality of life? The University
      of Florida experience.
AB  - BACKGROUND: Health-related quality of life (HRQoL) is an important clinical end
      point in evaluating the overall success of lung transplantation. The primary
      purpose of this study, therefore, was to document the degree of change in HRQoL
      in a sample of patients evaluated before and after lung transplantation. METHODS:
      Sixty-six adults who underwent single or bilateral lung transplantation at the
      University of Florida between March 1994 and May 2001 completed assessments of
      HRQoL (SF-36 Health Survey, Transplant Symptom Frequency Questionnaire), both
      before and after transplant. Pre- and post-transplant assessments of forced
      expiratory volume in 1 second (FEV1) percent predicted and 6-minute walk test
      performance were also obtained. RESULTS: HRQoL before transplant was
      significantly lower than in normative samples of chronic obstructive pulmonary
      disease (COPD) patients and adults in the general population. However, repeated
      measures analyses of co-variance showed significant improvements on 7 of 8 SF-36
      sub-scales, as well as the physical component summary and the mental component
      summary. Improvements in FEV1 percent predicted and 6-minute walk test
      performance were also found. Patients with longer time since transplantation
      reported more frequent and problematic symptoms commonly associated with
      immunosuppression, including depression, headaches and changes in physical
      appearance, among others. CONCLUSIONS: Lung transplantation appears to yield
      significant HRQoL benefits for patients. Many patients do, however, experience
      frequent symptoms associated with immunosuppression that may limit the full
      benefit of transplantation, and some of these symptoms appear to worsen over
      time. Future research efforts should focus on the development, implementation and
      evaluation of clinical interventions designed to optimize HRQoL both before and
      after lung transplantation.

PMID- 15949738
TI  - Emergent mechanical support in the community: improvement with early transplant
      center referral.
AB  - Emergent mechanical support for the failing ventricle, with eventual transfer for
      definitive care, is often required at non-transplant centers. Transfer for
      definitive care, in terms of bridge to transplant, may require ventricular assist
      device (VAD) placement at the primary institution or at the transplant center.
      Review of consecutive single transplant center referrals was conducted to
      decipher optimal management. From January 1997 to December 2000, 104 patients
      were transferred to the University of Pennsylvania Heart Failure/Transplant
      Service. Most were transferred from active cardiac surgical programs, with 56
      patients having post-cardiotomy failure at the primary site. A VAD was placed in
      procedures done at the outside hospital (OSH) in 28 patients, most commonly (60%)
      an Abiomed device. Of the 76 patients that received a VAD at the transplant
      center (TxpC), 86% received a TCI or Thoratec device. Biventricular support was
      required in 34 patients. Overall survival was 57%, with 54 patients bridged to
      transplantation and 5 patients undergoing recovery. Patients having a VAD placed
      at the OSH had a 32% (9 of 28) survival, whereas at the TxpC survival was 65% (45
      of 76) (p < 0.05). Mid-term follow-up showed that all 5 patients weaned are
      presently alive, and 52 patients are alive at >1-year post-transplant. The most
      common cause of death was multi-system organ failure (19 of 45), followed by
      major neurologic event (15 of 45). Infection was the cause of death in only 6
      patients. Left ventricular failure can be treated by emergent VAD placement.
      Overall survival is substantial if these patients are referred to a transplant
      center with multiple options. In contrast to previous reports, survival rates may
      be improved by earlier referral, before VAD placement at non-transplant centers
      and use of a VAD with longer-term capability.

PMID- 15949739
TI  - Experience of percutaneous coronary intervention in the management of pediatric
      cardiac allograft vasculopathy.
AB  - In a retrospective study, we examined the procedural success rate and the short-,
      intermediate-, and long-term outcomes of coronary interventional procedures in
      children with cardiac allograft vasculopathy. Seven patients underwent 13
      interventional procedures: balloon angioplasty alone (n = 3), angioplasty with
      stenting (n = 9), or angioplasty with brachytherapy (n = 1), with procedural
      success in all. Two major complications (cardiac arrest) and a single death
      occurred in the immediate postprocedural period. Five (83%) of the remaining 6
      patients developed moderate to severe restenosis, diffuse disease, or progressive
      vasculopathy; 3 have been retransplanted, 1 died from progressive cardiac
      allograft vasculopathy, and 1 is awaiting retransplantation, 40 months after the
      procedure.

PMID- 15949740
TI  - West Nile virus infection after cardiac transplantation.
AB  - West Nile virus is a mosquito-borne RNA Flavivirus infection transmitted to
      humans and other vertebrates, mainly by the Culex species of mosquito. Since the
      mid-1990s, the frequency and apparent clinical severity of West Nile virus
      outbreaks have increased. We report the case of a patient who developed West Nile
      virus encephalitis shortly after undergoing cardiac transplantation. Clinicians
      should be aware of the possibility of West Nile virus infection in transplant
      recipients and in patients receiving blood transfusions.

PMID- 15949741
TI  - Severe left ventricular dysfunction secondary to primary pulmonary hypertension:
      bridging therapy with bosentan before lung transplantation.
AB  - When right ventricular failure develops secondary to primary pulmonary
      hypertension, right-left ventricular interaction may lead to severe impairment of
      left ventricular function. In such cases, many experts favor combined heart-lung
      transplantation by fear that the left ventricle may not recover after
      transplantation of the lungs alone. We report a case of primary pulmonary
      hypertension with severely diminished right and left ventricular function. The
      patient was rendered amenable to isolated pulmonary transplantation with the
      endothelin-receptor antagonist bosentan. The medication improved right and left
      ventricular function to the point that heart transplantation no longer appeared
      necessary. After double-lung transplantation the patient's cardiac function made
      a full recovery. This approach might be particularly welcome considering both the
      current donor organ shortage and the limited number of surgical teams with
      expertise in heart-lung transplantation.

PMID- 15949742
TI  - Isolated ventricular non-compaction in adults with idiopathic cardiomyopathy:
      cardiac magnetic resonance and pathologic characterization of the anomaly.
AB  - Non-compaction of the ventricular myocardium is an anomaly of myocardial
      morphogenesis that leads to persistence of the embryonic myocardium with an
      excessively prominent trabecular meshwork and deep intertrabecular recesses. This
      report describes 3 cases of isolated left ventricular non-compaction in adults
      leading to terminal heart failure. We describe their distinctive myocardial
      histopathology and prospective diagnosis by cardiac magnetic resonance imaging
      (CMR). Heart transplantation was the only treatment option for all 3 of these
      severely ill patients. Isolated ventricular non-compaction should be considered
      in patients with severe idiopathic cardiomyopathy whose symptoms appear in early
      adulthood, and consideration given for early transplantation. Non-invasive
      imaging with CMR can confirm the diagnosis.

PMID- 15949743
TI  - NMR spectroscopy in inhomogeneous B0 and B1 fields with non-linear correlation.
AB  - Resolved NMR spectra from samples in inhomogeneous B0 and B1 fields can be
      obtained with the so-called "ex situ" methodology, employing a train of composite
      or adiabatic z-rotation RF pulses to periodically refocus the inhomogeneous
      broadening during the detection of the time-domain signal. Earlier schemes relied
      on a linear correlation between the inhomogeneous B0 and B1 fields. Here the
      pulse length, bandwidth, and amplitude of the adiabatic pulses of the hyperbolic
      secant type are adjusted to improve the refocusing for a setup with non-linear
      correlation. The field correlation is measured using a two-dimensional nutation
      experiment augmented with a third dimension with varying RF carrier frequency
      accounting for off-resonance effects. The pulse optimization is performed with a
      computer algorithm using the experimentally determined field correlation and a
      standard adiabatic z-rotation pulse as a starting point for the iterative
      optimization procedure. The shape of the z-rotation RF pulse is manipulated to
      provide refocusing for the conditions given by the sample-, magnet-, and RF-coil
      geometry.

PMID- 15949744
TI  - Homo-nuclear 13C J-decoupling in uniformly 13C-enriched solid proteins.
AB  - Recently, we reported an analysis of carbon lineshapes in high resolution solid
      state NMR spectra of uniformly 13C-enriched amino acids. Application of a 13C J
      decoupling protocol during the carbon chemical shift evolution period allowed us
      to separate the contribution of the second-order dipolar shift from that of the
      13C-13C J-coupling interactions to carbon linewidths. In this work, we have
      extended this approach to microcrystalline proteins. We describe the performance
      of the J-decoupling sequence applied to remove homo-nuclear 13C J-couplings in
      the 13C spectra of ubiquitin. Analysis of the J-decoupling efficiency for
      C(alpha) and carbonyl protein sites showed that a significant gain in resolution
      can be achieved.

PMID- 15949745
TI  - Solid-state 27Al MRI and NMR thermometry for catalytic applications with
      conventional (liquids) MRI instrumentation and techniques.
AB  - Multidimensional images of Al2O3 pellets, cordierite monolith, glass tube,
      polycrystalline V2O5 and other materials have been detected by 27Al, 51V, and
      23Na NMR imaging using techniques and instrumentation conventionally employed for
      imaging of liquids. These results demonstrate that, contrary to the widely
      accepted opinion, imaging of "rigid" solids does not necessarily require
      utilization of solid state NMR imaging approaches, pulse sequences and hardware
      even for quadrupolar nuclei which exhibit line widths in excess of 100 kHz, such
      as 51V in polycrystalline V2O5. It is further demonstrated that both 27Al NMR
      signal intensity and spin-lattice relaxation time decrease with increasing
      temperature and thus can potentially serve as temperature sensitive parameters
      for spatially resolved NMR thermometry.

PMID- 15949746
TI  - Spin-echo MRS in humans at high field: LASER localisation using FOCI pulses.
AB  - Significant improvements in spin-echo MRS are possible when voxel localisation is
      performed using high bandwidth frequency offset corrected inversion (FOCI) pulses
      as opposed to more conventional lower bandwidth pulses. The reduced chemical
      shift displacement errors result in a spectrum that more accurately reflects the
      actual metabolite distribution within any region of interest that is selected
      graphically on a series of scout images, and can lead to improved metabolite
      detection in the case of homonuclear J-coupled spins. At 4.7T, FOCI pulses with a
      20 kHz bandwidth result in extremely sharp and uniform selection profiles, and
      negligible contamination from outside of the voxel of interest, for all signals
      in the 1H spectral range that is normally studied. A 'FOCI' adiabatic half
      passage is observed to provide good excitation over the 1H spectral range. Single
      shot performance with echo-time (TE)48 ms is reported using a four-port drive
      birdcage head coil. GAMMA simulations show that, for many detectable metabolites
      at 4.7 T, LASER localisation using FOCI pulses with TE=48 ms results in 1H anti
      phase spectral components that are the same order as would be obtained from a
      symmetric PRESS sequence with TE=32 ms. Timing schemes are proposed to enable
      good measurement of lactate with very little signal loss arising from chemical
      shift displacement errors at TE=144 and 288 ms.

PMID- 15949747
TI  - Rapid-scan EPR with triangular scans and fourier deconvolution to recover the
      slow-scan spectrum.
AB  - Direct-detected rapid-scan EPR signals were recorded using triangular field scan
      rates between 1.7 and 150 kG/s for deoxygenated samples of lithium phthalocyanine
      (LiPc) and Nycomed trityl-CD3. These scan rates are rapid relative to the
      reciprocals of the electron spin relaxation times and cause characteristic
      oscillations in the signals. Fourier deconvolution with an analytical function
      permitted recovery of lineshapes that are in good agreement with experimental
      slow-scan spectra. Unlike slow-scan EPR, direct detection rapid-scan EPR does not
      use phase sensitive detection and records the absorption signal directly instead
      of the first derivative of the absorption signal. The amplitude of the signal
      decreases approximately linearly with applied magnetic field gradient. Images of
      phantoms constructed from samples of LiPc and trityl-CD3 were reconstructed by
      filtered back-projection from data sets with a missing angle. The lineshapes in
      spectral slices from the image are in good agreement with slow-scan spectra and
      the spacing between sample tubes matches well with the known sample geometry.

PMID- 15949748
TI  - The proton nuclear magnetic shielding tensors in biphenyl: experiment and theory.
AB  - Line-narrowing multiple pulse techniques are applied to a spherical sample
      crystal of biphenyl. The 10 different proton shielding tensors in this compound
      are determined. The accuracy level for the tensor components is 0.3 ppm. The
      assignment of the measured tensors to the corresponding proton sites is given
      careful attention. Intermolecular shielding contributions are calculated by the
      induced magnetic point dipole model with empirical atom and bond susceptibilities
      (distant neighbours) and by a new quantum chemical method (near neighbours).
      Subtracting the intermolecular contributions from the (correctly assigned)
      measured shielding tensors leads to isolated-molecule shielding tensors for which
      there are symmetry relations. Compliance to these relations is the criterion for
      the correct assignment. The success of this program indicates that intermolecular
      proton shielding contributions can be calculated to better than 0.5 ppm. The
      isolated-molecule shielding tensors obtained from experiment and calculated
      intermolecular contributions are compared with isolated-molecule quantum chemical
      results. Expressed in the icosahedral tensor representation, the rms differences
      of the respective tensor components are below 0.5 ppm for all proton sites in
      biphenyl. In the isolated molecule, the least shielded direction of all protons
      is the perpendicular to the molecular plane. For the para proton, the
      intermediate principal direction is along the C-H bond. It is argued that these
      relations also hold for the protons in the isolated benzene molecule.

PMID- 15949749
TI  - Chromium(III) complexes as intermolecular probes.
AB  - Metal ion complexes provide flexible paramagnetic centers that may be used to
      define intermolecular contacts in a variety of solution phase environments
      because both the charge and electronic relaxation properties of the complex may
      be varied. For most complex ions, there are several proton equilibria that may
      change the effective charge on the complex as a function of pH which in turn
      affects the efficacy of application for defining the electrostatic surfaces of co
      solute molecules. We report here spectrophotometric and nuclear spin relaxation
      studies on aqueous solutions of chromium(III) complexes of EDTA, DTPA, and bis
      amides of both. The effective charges available from these paramagnetic centers
      range from -3 to +1 and we report the pH ranges over which the effective charge
      is defined with confidence for application in magnetic relaxation experiments.

PMID- 15949750
TI  - Non-destructive observation of electrically detected magnetic resonance in bulk
      material using AC bias.
AB  - DC bias is normally found in conventional measurements of electrically detected
      magnetic resonance (EDMR). Usually, electrodes are formed on the sample surface
      to make ohmic contacts for detecting changes in the electrical characteristics of
      the sample material. Thus, destructive procedures are required to detect the EDMR
      signal of bulk material with such methods. An AC bias detection technique was
      developed to allow the non-destructive EDMR measurement of bulk materials. An AC
      bridge circuit was constructed to detect the change in impedance of the sample,
      which when changed by ESR, an unbalanced AC voltage can be detected. By detecting
      this AC bias, it is possible to cancel the effects, such as Shottky barriers,
      that disturb the ohmic contact between the electrodes and a sample material.
      Further, the AC bias current penetrates the thin surface layer of a sample such
      as silicon oxide, which normally obstructs a DC current. This method was utilized
      using conductive rubber contacts for non-destructive EDMR measurements of part of
      a silicon wafer. EDMR spectra observed were the same as those obtained by the
      conventional method of using DC bias detection.

PMID- 15949751
TI  - Spectral analysis of multichannel MRS data.
AB  - The use of phased-array receive coils is a well-known technique to improve the
      image quality in magnetic resonance imaging studies of, e.g., the human brain. It
      is common to incorporate proton (1H) magnetic resonance spectroscopy (MRS)
      experiments in these studies to quantify key metabolites in a region of interest.
      Detecting metabolites in vivo is often difficult, requiring extensive scans to
      achieve signal-to-noise ratios (SNR) that provide suitable diagnostic results.
      Combining the MR absorption spectra obtained from several receive coils is one
      possible approach to increase the SNR. Previous literature does not give a clear
      overview of the wide range of possible approaches that can be used to combine MRS
      data from multiple detector coils. In this paper, we consider the multicoil MRS
      approach and introduce several signal processing tools to address the problem
      from different nonparametric, semiparametric, and parametric perspectives,
      depending on the amount of available prior knowledge about the data. We present a
      numerical study of these tools using both simulated 1H MRS data and experimental
      MRS data acquired from a 3T MR scanner.

PMID- 15949752
TI  - Quantitative study of the effects of chemical shift tolerances and rates of SA
      cooling on structure calculation from automatically assigned NOE data.
AB  - The calculation of protein structures from nuclear magnetic resonance (NMR) data
      has been greatly facilitated by improvements in software for the automatic
      assignment of NOESY spectra. Nevertheless, for larger proteins, resonance overlap
      may lead to an overwhelming number of assignment options per peak. Although most
      software for automatic NOESY assignment can deal with a certain level of
      assignment ambiguity, structure calculations fail when this becomes too high.
      Reducing the number of assignment options per peak by reducing the chemical shift
      tolerances can lead to correct assignments being excluded, and thus also to
      incorrect structures. We have investigated, systematically, for three proteins of
      different size, the influence of the chemical shift tolerance limits (Delta) and
      of the number of simulated annealing (SA) cooling steps on the performance of the
      software ARIA. Large tolerance windows, and the correspondingly high levels of
      ambiguity, did not cause problems when appropriately slower cooling was used in
      our SA protocol. In cases where a high percentage of well-converged structures
      was not achieved, we demonstrate that it is more productive to calculate fewer
      structures whilst applying slow cooling, than to calculate many structures with
      fast cooling. In this way, high-quality structures were obtained even for
      proteins whose NMR spectra showed great degeneracy, and where there was much
      inconsistency in peak alignment between different samples. The method described
      herein opens the way to the automated structure determination of larger proteins
      from NMR data.

PMID- 15949753
TI  - NMR spectroscopy of proteins encapsulated in a positively charged surfactant.
AB  - Traditionally, large proteins, aggregation-prone proteins, and membrane proteins
      have been difficult to examine by modern multinuclear and multidimensional
      solution NMR spectroscopy. A major limitation presented by these protein systems
      is that their slow molecular reorientation compromises many aspects of the more
      powerful solution NMR methods. Several approaches have emerged to deal with the
      various spectroscopic difficulties arising from slow molecular reorientation. One
      of these takes the approach of actively seeking to increase the effective rate of
      molecular reorientation by encapsulating the protein of interest within the
      protective shell of a reverse micelle and dissolving the resulting particle in a
      low viscosity fluid. Since the encapsulation is largely driven by electrostatic
      interactions, the preparation of samples of acidic proteins suitable for NMR
      spectroscopy has been problematic owing to the paucity of suitable cationic
      surfactants. Here, it is shown that the cationic surfactant CTAB may be used to
      prepare samples of encapsulated anionic proteins dissolved in low viscosity
      solvents. In a more subtle application, it is further shown that this surfactant
      can be employed to encapsulate a highly basic protein, which is completely
      denatured upon encapsulation using an anionic surfactant.

PMID- 15949754
TI  - Frequency offset refocused PISEMA-type sequences.
AB  - The popular PISEMA experiment is highly sensitive to the 1H chemical shift
      dispersion and the choice of the 1H carrier frequency. This is due to the off
      resonance 1H irradiation in the FSLG-CP sequence employed during the dipolar
      evolution period. In the modified approach described in this work, the
      interfering frequency offset terms are suppressed. In the new pulse schemes,
      conventional FSLG-CP is intercalated with 180 degrees pulses applied
      simultaneously to both frequency channels, and with phases set orthogonal to
      those of the spin-lock fields. The technique is demonstrated on a nematic liquid
      crystalline sample. Extensions to amplitude-modulated FSLG-CP recoupling under
      MAS are also presented.

PMID- 15949755
TI  - Rapid assignment of protein side chain resonances using projection-reconstruction
      of (4,3)D HC(CCO)NH and intra-HC(C)NH experiments.
AB  - The reconstruction of higher-dimensional NMR spectra from projections can provide
      significant savings in instrument time. Here, we demonstrate its application to
      the (4,3)D HC(CCO)NH and intra-HC(C)NH experiments. The latter experiment
      contains a novel intra-residue filter element, which selectively correlates the
      side chain resonances with the corresponding intra-residue amide resonances.
      Compared to the conventional HC(C)NH experiment, the intra-HC(C)NH experiment
      reduces the spectral complexity and thus the minimum number of projections
      required for artifact-free reconstruction by half. The use of the projection
      reconstruction technique allows rapid data collection and unambiguous assignment
      of aliphatic side chain nuclei at high resolution.

PMID- 15949756
TI  - Be fruitful and multiply: gene amplification inducing pathogen resistance.
AB  - The majority of European spring barley cultivars have broad-spectrum powdery
      mildew resistance conditioned by a naturally occurring recessive resistance
      allele at the Mlo locus that originates from Ethiopian landraces. A recent
      publication by Pietro Piffanelli et al. describes an unusual amplification of
      gene segments upstream of the Mlo promoter that probably interferes with
      transcription and is responsible for gene inactivation. Their findings provide
      insights into the breeding events during the domestication of wild barley.

PMID- 15949757
TI  - Is there more than one way to attract a pollen tube?
AB  - ZmEA1 (Zea mays egg apparatus 1) is expressed only in the egg and synergid cells.
      Embryo sacs with presumed reduced expression of ZmEA1 fail to attract pollen
      tubes. Together with data from Arabidopsis mutants and from elegant laser
      ablation experiments in Torenia fournieri, these results indicate that embryo
      sacs send signals to the incoming pollen tubes. We need to decipher how such
      signals are perceived and determine if the signals are species-specific.

PMID- 15949758
TI  - Lipid microdomains--plant membranes get organized.
AB  - The plant plasma membrane is now known to be a more sophisticated structure than
      was previously thought. Sebastien Mongrand et al. and Georg Borner et al. have
      isolated specific plasma membrane microdomains ('lipid rafts') that are enriched
      in sterols and sphingolipids. These rafts contain distinct sets of proteins and
      might help to explain how plasma membrane proteins are positioned in certain
      parts of the cell to function in development and signalling.

PMID- 15949759
TI  - It runs in the family: regulation of brassinosteroid signaling by the BZR1-BES1
      class of transcription factors.
AB  - Research of the molecular events underlying brassinosteroid (BR) signaling is
      emerging as a new paradigm for studying plant hormone signal transduction
      pathways. Two recent reports have shown that the BZR1-BES1 family of proteins is
      a class of novel plant-specific transcription factors that directly bind to and
      regulate BR-responsive genes, thus filling in key details of the link between
      hormonal signal transmission in the cytoplasm and transcriptional status change
      in the nucleus.

PMID- 15949760
TI  - Insect host location: a volatile situation.
AB  - Locating a host plant is crucial for a phytophagous (herbivorous) insect to
      fulfill its nutritional requirements and to find suitable oviposition sites.
      Insects can locate their hosts even though the host plants are often hidden among
      an array of other plants. Plant volatiles play an important role in this host
      location process. The recognition of a host plant by these olfactory signals
      could occur by using either species-specific compounds or specific ratios of
      ubiquitous compounds. Currently, most studies favor the second scenario, with
      strong evidence that plant discrimination is due to central processing of
      olfactory signals by the insect, rather than their initial detection.
      Furthermore, paired or clustered olfactory receptor neurons might enable fine
      scale spatio-temporal resolution of the complex signals encountered when
      ubiquitous compounds are used.

PMID- 15949761
TI  - Proteins, chlorophylls and lipids: X-ray analysis of a three-way relationship.
AB  - Photosynthetic reaction centres and light harvesting complexes have been at the
      forefront of crystallographic studies of integral membrane proteins. In recent
      years, there have been spectacular advances in our understanding of the structure
      of (bacterio)chlorophyll-containing membrane proteins from oxygenic and
      anoxygenic phototrophs. In these complex structures, the protein scaffold encases
      different combinations of cofactors and interacts with several tightly bound
      lipid species that play a variety of hitherto unrecognized structural roles. Some
      of these lipids have relevance to the physiological function of the protein,
      whereas others are important for the formation of highly ordered crystals. The
      first site-directed mutagenesis studies of individual lipid binding sites have
      now underlined the importance of the lipid component for the structural stability
      of protein-cofactor-lipid complexes.

PMID- 15949762
TI  - Paramutation: an encounter leaving a lasting impression.
AB  - Paramutation is the result of heritable changes in gene expression that occur
      upon interaction between alleles. Whereas Mendelian rules, together with the
      concept of genetic transmission via the DNA sequence, can account for most
      inheritance in sexually propagating organisms, paramutation-like phenomena
      challenge the exclusiveness of Mendelian inheritance. Most paramutation-like
      phenomena have been observed in plants but there is increasing evidence for its
      occurrence in other organisms, including mammals. Our knowledge of the underlying
      mechanisms, which might involve RNA silencing, physical pairing of homologous
      chromosomal regions or both, is still limited. Here, we discuss the
      characteristics of different paramutation-like interactions in the light of
      arguments supporting each of these alternative mechanisms.

PMID- 15949763
TI  - Eto Brute? Role of ACS turnover in regulating ethylene biosynthesis.
AB  - Ethylene influences many plant growth and developmental processes. To achieve
      this diversity of function, the biosynthesis of this gaseous hormone is tightly
      regulated by a diverse array of factors, including developmental cues, wounding,
      biotic and abiotic stresses, and other phytohormones. Many studies have
      demonstrated that differential transcription of 1-aminocyclopropane-1-carboxylate
      synthase (ACS) gene family members is an important factor regulating ethylene
      production in response to different stimuli. Recently, several studies, focusing
      primarily on the Arabidopsis eto mutants, have indicated that the regulation of
      ACS protein stability also plays a significant role in the control of ethylene
      biosynthesis. Here, we review this post-transcriptional control of ethylene
      biosynthesis and discuss the mechanisms that underlie it.

PMID- 15949764
TI  - To clone or not to clone plant QTLs: present and future challenges.
AB  - Recent technical advancements and refinement of analytical methods have enabled
      the loci (quantitative trait loci, QTLs) responsible for the genetic control of
      quantitative traits to be dissected molecularly. To date, most plant QTLs have
      been cloned using a positional cloning approach following identification in
      experimental crosses. In some cases, an association between sequence variation at
      a candidate gene and a phenotype has been established by analysing existing
      genetic accessions. These strategies can be refined using appropriate genetic
      materials and the latest developments in genomics platforms. We foresee that
      although QTL analysis and cloning addressing naturally occurring genetic
      variation should shed light on mechanisms of plant adaptation, a greater emphasis
      on approaches relying on mutagenesis and candidate gene validation is likely to
      accelerate the pace of discovering the genes underlying QTLs.

PMID- 15949765
TI  - Antibiotics rescue neurons from glutamate attack.
AB  - L-glutamate is the major excitatory neurotransmitter in the brain and is
      responsible for normal brain function. However, high glutamate exposure triggers
      neuronal death, a process known as excitotoxicity. Excitotoxicity is associated
      with acute and chronic neurodegenerative diseases. Treating excitotoxicity using
      glutamate-receptor antagonists has not proven clinically viable, necessitating
      more sophisticated approaches. Rothstein and colleagues discovered that beta
      lactam antibiotics protect neurons from excitotoxicity by increasing the number
      of glutamate transporters, which have a key role in clearing glutamate from the
      extracellular space. The design of compounds capable of modulating glutamate
      uptake represents a novel strategy for the treatment of neurodegenerative
      diseases.

PMID- 15949766
TI  - Does chasing selected 'Fox' to the nucleus prevent diabetes?
AB  - Foxa2 (Hnf3beta) is a winged-helix/forkhead transcription factor that regulates
      gene expression in the liver, pancreatic islets and adipocytes. It is required
      for the maintenance of glucose and lipid homeostasis. Hyperinsulinemia-mediated
      inactivation of Foxa2 by nuclear exclusion has recently been implicated in the
      development of liver steatosis and insulin resistance in three animal models of
      diabetes. These abnormalities were cured by adenovirus-mediated expression of a
      constitutively active form of Foxa2 containing a mutated T156 phosphorylation
      site, which increases fatty acid oxidation and reduces its biosynthesis.
      Accordingly, the prevention of phosphorylation of Foxa2 was suggested as a
      pharmacological target for the treatment of obesity and diabetes.

PMID- 15949767
TI  - The OXE receptor: a new therapeutic approach for asthma?
AB  - The eicosanoid 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) has recently
      been identified as the ligand for the oxoeicosanoid (OXE) receptor. In vitro and
      in vivo studies have suggested that 5-oxo-ETE has a role in the asthmatic
      inflammatory response and it has been shown to stimulate eosinophil migration to
      the airways. New data suggest that eosinophils have an important role in the
      pathogenesis of asthma, being required for mucus accumulation, airway
      hyperresponsiveness and remodelling of the airways. However, there are several
      mediators that can stimulate the recruitment of eosinophils to the airways and
      the development of antagonists against the OXE receptor is required to evaluate
      the potential of the OXE receptor as a new therapeutic approach for asthma.

PMID- 15949768
TI  - Regenerative medicine: a radical reappraisal of the spleen.
AB  - The spleen has long been considered a dispensable organ. Recent research,
      however, has found that the spleen of adult mice holds a reservoir of stem cells
      that can rapidly and robustly differentiate into functional cells of diverse
      lineages. Splenic stem cells express Hox11, a key embryonic transcription factor
      that regulates organogenesis. The presence of multi-lineage stem cells in the
      spleen might represent lifelong persistence of cells from a primitive embryonic
      region called the aorta-gonad-mesonephros. By bringing together findings from
      diverse disciplines, we propose that the adult spleen is an important source of
      multi-lineage stem cells for future cellular therapies for diabetes and other
      diseases.

PMID- 15949769
TI  - Bilirubin and the risk of common non-hepatic diseases.
AB  - Bilirubin is a potent antioxidant but can be toxic at high concentrations. This
      article critically reviews the reported relationships of plasma bilirubin levels
      to the severity and/or incidence of various common non-hepatic diseases. Plasma
      bilirubin levels are reportedly negatively related to the risk of atherosclerotic
      diseases, cancers, demyelinating neuropathies and seasonal affective disorder. By
      contrast, the incidence and severity of schizophrenia are increased by elevated
      bilirubin levels. The data strongly suggest that the level of plasma bilirubin
      should be considered as a risk factor for several common non-hepatic diseases.
      Additional studies are needed to clarify the mechanisms of this influence, which
      are thought to be related to unconjugated bilirubin counteracting the oxidative
      stress underlying these disorders.

PMID- 15949770
TI  - Cancer therapy: can the challenge be MET?
AB  - The deregulation of tyrosine kinase receptors (RTKs) is frequent in human tumors
      and is often associated with the acquisition of an aggressive phenotype. The Met
      oncogene, encoding the RTK for hepatocyte growth factor (HGF), controls genetic
      programs leading to cell growth, invasion and protection from apoptosis. The
      deregulated activation of Met is crucial not only for the acquisition of
      tumorigenic properties but also to achieve an invasive phenotype. The involvement
      of MET in human tumors has been definitively established and can be achieved
      through several mechanisms, including MET interaction with unrelated membrane
      receptors, such as integrins, plexins, CD44, FAS and other RTKs. Interfering with
      Met activation is thus a new and challenging approach to hamper tumorigenic and
      metastatic processes.

PMID- 15949771
TI  - Developments in transgenic technology: applications for medicine.
AB  - Recent advances in the efficiency of transgenic technology have important
      implications for medicine. The production of therapeutic proteins from animal
      bioreactors is well established and the first products are close to market. The
      genetic modification of pigs to improve their suitability as organ donors for
      xenotransplantation has been initiated, but many challenges remain. The use of
      transgenesis, in combination with the method of RNA interference to knock down
      gene expression, has been proposed as a method for making animals resistant to
      viral diseases, which could reduce the likelihood of transmission to humans.
      Here, the latest developments in transgenic technology and their applications
      relevant to medicine and human health will be discussed.

PMID- 15949772
TI  - Emerging therapeutic approaches for osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is an incurable genetic brittle-bone disease.
      Although drug therapy, surgery and physiotherapy represent current treatments for
      OI, the search is ongoing for effective and innovative new therapies targeting
      the underlying causes of the disease. In this regard, recent advances in the
      fields of gene and stem-cell therapies have been considerable. In spite of the
      many challenges that remain, potential new therapies for OI, which have been
      tested in cell culture systems, animal models and patients, offer hope for the
      future development of successful therapies. Recent progress in the field is
      reviewed here.

PMID- 15949774
TI  - Trend in methodological quality of randomised clinical trials in low back pain.
AB  - During the past decades, the number of published randomised clinical trials
      evaluating the efficacy of conservative treatments for low back pain has
      substantially increased. At the same time several initiatives were undertaken in
      order to improve the methodological quality of published randomised clinical
      trials, also in the field of low back pain. We investigated how the
      methodological quality of randomised clinical trials in the field of low back
      pain developed over time since the first published trial in 1961. Methodological
      scores of 269 RCTs included in 15 Cochrane reviews of conservative treatment for
      low back pain were compared. Overall many trials showed methodological
      shortcomings. The median overall quality scores ranged from 36 to 82% depending
      on the type of intervention. There were no improvements in median overall
      methodological quality over time from 1960 to 2004. Improvements were apparent
      for a few validity criteria only.

PMID- 15949775
TI  - How to prevent low back pain.
AB  - This chapter summarizes the European Guidelines for Prevention in Low Back Pain,
      which consider the evidence in respect of the general population, workers and
      children. There is limited scope for preventing the incidence (first-time onset)
      of back pain and, overall, there is limited robust evidence for numerous aspects
      of prevention in back pain. Nevertheless, there is evidence suggesting that
      prevention of various consequences of back pain is feasible. However, for those
      interventions where there is acceptable evidence, the effect sizes are rather
      modest. The most promising approaches seem to involve physical activity/exercise
      and appropriate (biopsychosocial) education, at least for adults. Owing to its
      multidimensional nature, no single intervention is likely to be effective at
      preventing the overall problem of back pain, although there is likely to be
      benefit from getting all the players onside. However, innovative studies are
      required to better understand the mechanisms and delivery of prevention in low
      back pain.

PMID- 15949776
TI  - What diagnostic tests are useful for low back pain?
AB  - Low back pain (LBP) is a common problem that poses some interesting and difficult
      diagnostic problems. It is typically benign and self-limited, but it is
      occasionally the presenting symptom of serious systemic disease. The general
      diagnostic approach to low back pain is to check for 'red flags' in the history
      and physical that suggest the presence of malignancy, infection or
      spondyloarthridites, and for neurological compromise that could indicate that
      surgery is required (cauda equina syndrome) or may be beneficial (such as
      herniated discs or spinal stenosis that have not improved with conservative
      care). In the absence of these features, imaging is of limited value. Recent
      research has begun to evaluate subgroups with 'non-specific' low back pain that
      seem to benefit from specific interventions such as median branch or sacroiliac
      joint injections, manipulation, or specific exercises, but these require further
      investigation and validation.

PMID- 15949777
TI  - How to identify patients with a poor prognosis in daily clinical practice.
AB  - Predicting poor outcomes in daily practice is challenging. As well as prior
      episodes of low back pain and pain intensity, various psychosocial risk factors
      have been identified, although the independent prognostic value of these is
      rather low. This supports the necessity for a multidimensional view of the
      transition from acute to chronic pain and/or the development of disability.
      Psychological distress has been found to increase the risk of such a transition.
      Patients' beliefs and expectations about their pain seem to influence the
      recovery process; pain-related fear and fear avoidance can be influential
      psychological variables, from pain inception to its chronic stage. The influence
      of occupational factors such as job satisfaction, low workplace support or
      physical workload has also been emphasized. Treatment provider factors and the
      relationship between patients and care providers also contribute to the realistic
      or unrealistic expectations and meaningful or acceptable outcomes.

PMID- 15949778
TI  - Clinically important outcomes in low back pain.
AB  - Four important domains directly related to low back pain are: pain intensity, low
      back-pain-specific disability, patient satisfaction with treatment outcome, and
      work disability. Within each of the domains, different questionnaires have been
      proposed. This chapter focuses on validated and widely used questionnaires.
      Details of the background and the measurement properties, and of the minimally
      clinically important change (MCIC) using these questionnaires, are described. The
      MCIC can be estimated using various methods and there is no consensus in the
      literature on what the most appropriate technique is. This chapter focuses
      primarily on two adequate and frequently used methods for estimating the MCIC. We
      argue that the MCIC should not be considered as a fixed value and that the MCIC
      values presented in this chapter are used as indications. For patients with
      subacute or chronic low back pain, the MCIC for pain on a visual analogue scale
      (VAS) should at least be 20mm and for acute low back pain it seems reasonable to
      suggest that the MCIC should at least be at the level of approximately 35mm. If a
      numerical rating scale (NRS) is used it seems reasonable to suggest that the MCIC
      should at least be 3.5 and 2.5 for patients with acute and chronic low back pain,
      respectively. For functional disability as measured with the Roland Disability
      Questionnaire it seems reasonable that the MCIC should at least be 3.5 points,
      whereas an MCIC of at least 10 points when the Oswestry Disability Index is used.
      For global perceived effect, we argue that the MCIC is most appropriately defined
      in terms of at least 'much improved' or 'very satisfied', instead of including
      'slightly improved'. Finally, we argue that, from the point of view of cost
      effectiveness, every day of earlier return to work is important. The exact value
      for the MCIC can be determined, taking into account the aim of the measurement,
      the initial scores, the target population and the method used to assess MCIC.

PMID- 15949779
TI  - The use of medication in low back pain.
AB  - The choice of medication for low back pain should be evidence based and tailored
      as much as possible to suit the individual patient. Acetaminophen (paracetamol),
      mild opioids and NSAIDs are the first-line drugs for low back pain but there is
      no evidence that one is more effective than the others. Non-benzodiazepine muscle
      relaxants (with or without pain medication) could be considered as second-line
      drugs in acute low back pain, and cyclic antidepressants in chronic low back
      pain. The risk of adverse side effects can be reduced by taking account of the
      patient's medical history and by using a test dose. The realization that symptoms
      other than pain are sometimes more important and/or easier to overcome can
      increase the benefits of medication. The long-term effects of medication can be
      improved when it is combined with non-drug interventions.

PMID- 15949780
TI  - What is the value of physical therapies for back pain?
AB  - Some would say that the value of physical therapies for low back pain patients is
      the provision of pain relief; others argue that it is all about helping the
      person to get on with his or her life. There is an on-going debate amongst
      practitioners as to whether a hands-on or a hands-off approach is likely to be
      most effective for these patients. This chapter reviews these positions through
      an exploration of the literature. It examines the evidence for the effectiveness
      of a range of commonly used physical therapies.

PMID- 15949781
TI  - Complementary and alternative therapies for low back pain.
AB  - The support for the principles of evidence-based medicine has increased within
      the field of complementary and alternative medicine (CAM). The objective of this
      chapter is to determine the effectiveness of CAM therapies compared to placebo,
      no intervention, or other interventions for acute/subacute and chronic non
      specific low back pain (LBP). Results from Cochrane reviews on acupuncture,
      botanical medicine, massage, neuroreflexotherapy, and spinal manipulation have
      been used. The results showed that acupuncture is more effective than no
      treatment or sham treatment for chronic LBP but that there are no differences in
      effectiveness compared with other conventional therapies. Specific botanical
      medicines can be effective for acute episodes of chronic non-specific LBP in
      terms of short-term improvement in pain and functional status; long-term efficacy
      was not assessed. Massage seems more beneficial than sham treatment for chronic
      non-specific LBP but effectiveness compared with other conventional therapies is
      inconclusive. Neuroreflexotherapy appears to be more effective than sham
      treatment or standard care for chronic non-specific LBP. Spinal manipulation was
      more effective than sham manipulation or ineffective therapies, and equally
      effective as other conventional therapies. In summary, the results on CAM
      therapies for (acute episodes of) chronic LBP are promising but more evidence on
      the relative cost-effectiveness compared to conventional treatments is needed.

PMID- 15949782
TI  - Concepts of rehabilitation for the management of low back pain.
AB  - This chapter develops rehabilitation principles for the clinical and occupational
      management of non-specific low back pain (LBP). Rehabilitation has traditionally
      been a secondary intervention, which focused on permanent impairment, but this is
      inappropriate for LBP. Most patients with LBP do not have any irremediable
      impairment and long-term incapacity is not inevitable: given the right care,
      support and opportunity, most should be able to return to work. Rehabilitation
      should then address obstacles to recovery and barriers to (return to) work.
      Rehabilitation should not be a separate, second stage after 'treatment' is
      complete: rehabilitation principles should be integral to clinical and
      occupational management. It should be possible to reduce sickness absence and
      long-term incapacity due to LBP by at least 30-50%, but this will require a
      fundamental shift in management culture.

PMID- 15949783
TI  - What is the most cost-effective treatment for patients with low back pain? A
      systematic review.
AB  - Economic evaluations of the various interventions available for low back pain
      will help clinicians and policymakers to identify the most beneficial treatment.
      This chapter aims to evaluate the most cost-effective treatments for patients
      with non-specific low back pain. Pubmed, Embase and the Cochrane library were
      used to search for articles published from 1966 to July 2004 using a variety of
      keywords. References were checked to identify additional studies. The consensus
      health economic criteria (CHEC) list was used to assess the methodological
      quality of the studies. We found 17 studies; six of these concluded that the
      intervention of interest was superior to the control intervention. However,
      definite conclusions about the most cost-effective intervention could not be
      drawn because of the heterogeneity of interventions, controls and study
      populations. More high-quality economic evaluations are needed before such a
      conclusion can be made.

PMID- 15949784
TI  - Seasonal variation in the home range and host availability of the blood-sucking
      insect Mepraia Spinolai in wild environment.
AB  - In this study, we quantify the home range of Mepraia spinolai, a wild vector of
      Trypanosoma cruzi, and the abundance of wild mammals during summer and winter
      seasons in a protected area of north-central Chile. Results revealed significant
      differences between seasons for home range size and host availability. M.
      spinolai presented larger home range sizes, and mammal hosts were more abundant
      in summer, indicating that T. cruzi would have a higher probability of being
      transmitted during warmer months.

PMID- 15949785
TI  - Characterization of polyanion-protein complexes by frontal analysis continuous
      capillary electrophoresis and small angle neutron scattering: effect of polyanion
      flexibility.
AB  - The binding constant (K(obs)) for the beta-lactoglobulin-poly(vinylsulfate) (BLG
      PVS) complex was measured by frontal analysis continuous capillary
      electrophoresis at pH values above the isoelectric point of BLG, and the
      persistence length (L(p)) of PVS was measured by small angle neutron scattering,
      to examine the effect of polyelectrolyte chain stiffness on its binding
      efficiency to proteins. The values of K(obs) and L(p) were compared with those of
      BLG-PSS and BLG-PAMPS (poly(2-acrylamido-2-methylpropanesulfonate)) reported
      previously. The relationship between K(obs) and L(p) was reciprocal, indicating
      that protein binding is enhanced by the flexibility of the polyanion, at least in
      the case where the net protein charge is negative. In addition, at a fixed pH,
      the polymer systems displayed a similar ionic strength dependence of K(obs). This
      similarity was consistent with the proposal that the binding properties of PVS
      and PAMPS polyanions are governed purely by electrostatic interactions and are
      independent of their molecular structure.

PMID- 15949786
TI  - Miniaturization of absorbance assays using the fluorescent properties of white
      microplates.
AB  - Miniaturization of high-throughput screening (HTS) assays has several obvious
      advantages, including increased throughput and lower cost by reduction in reagent
      consumption. Although absorbance assays are widely used in research laboratories,
      their application for HTS in a low-volume format has been met with mixed success
      because they are difficult to miniaturize. Challenges for the miniaturization of
      absorbance assays include low signal due to short path lengths and meniscus
      distortions in small well sizes. Here we describe a method to miniaturize
      absorbance assays to standard, white, low-volume 384-well and 1536-well
      microplates using a fluorometric plate reader for detection. The premise of this
      absorbance assay is based on the fluorescent properties of white microplates and
      the ability of a colored product to quench the fluorescence signal from the plate
      by absorbing either the excitation light or the emission light. This method was
      applied to the detection of inorganic phosphate using Quinaldine red and
      Malachite green dyes and to the monitoring of alkaline phosphatase hydrolysis of
      p-nitrophenyl phosphate. These assays can be carried out in low volumes, give
      robust screening statistics, and can be accomplished with a simple, inexpensive
      fluorometric plate reader.

PMID- 15949787
TI  - Fatigue and damage to the masseter muscle by prolonged low-frequency stimulation
      in the rat.
AB  - This study aimed to examine peripheral fatigue and the resultant damage to the
      masseter muscle due to prolonged low-frequency stimulation. Thirty male rats were
      divided into S1, S2, S4, Dantr and Sham groups. The left masseters were used as
      experimental muscles. A pair of stimulation electrodes was placed on the left
      masseter. A stimulating session included rectangular electric pulses of 18 Hz (5
      mA, approximately 18 V, 0.7 ms) for 2 h with a 3 min rest period between
      sessions. One session was given to the S1 group, two sessions to the S2 group and
      four sessions to the S4 group. Four sessions were given to the Dantr group with
      administration of dantrolene to determine any artifacts of the electrical
      current. No electric stimulation was given to both side masseters in the Sham
      group or to the control (right) masseters in the other groups. In each session,
      jaw-closing force increased to a peak within 1 min and attenuated to the steady
      force. The peak force decreased as the session advanced in each group. Both side
      masseters were dissected after the stimulations and examined histologically. The
      experimental masseter was significantly heavier than that of the controls in the
      S1, S2 and S4 groups, and the muscle fibres showed irregularity of size and shape
      with enlargement of interstitial space and infiltration of mononuclear cells into
      the fibres. However, no such histological change was observed in the Dantr and
      Sham groups. It was confirmed that fatigue and damage to muscle fibres could be
      induced in masticatory muscles by prolonged low-frequency stimulation.

PMID- 15949788
TI  - Further aspects on the hemolytic activity of the antibiotic lipopeptide iturin A.
AB  - The bacterial lipopeptide iturin A is able to cause hemolysis of human
      erythrocytes in a dose-dependent manner. Hemolysis takes place at iturin
      concentrations below its critical micellar concentration. Relative kinetics
      determinations clearly show that K(+) leakage occurs prior to hemoglobin release.
      Furthermore, hemolysis can be prevented by addition to the outer solution of
      osmotic protectants of appropriate size. Altogether these results indicate that
      iturin A-induced hemolysis follows a colloid-osmotic mechanism, with the
      formation of a membrane pore of average diameter 32 A. Iturin A is capable of
      inducing leakage of an aqueous fluorescent probe trapped in human erythrocyte
      ghosts, but not in large unilamellar liposomes made of various lipid
      compositions. The different permeabilizing effects of iturin A on model and
      biological membranes are discussed on the light of the presented results.

PMID- 15949789
TI  - Non-COX-2 targets and cancer: expanding the molecular target repertoire of
      chemoprevention.
AB  - Chemoprevention represents a highly promising approach for the control of cancer.
      That nonsteroidal anti-inflammatory drugs (NSAIDs) prevent colon and other
      cancers has led to novel approaches to cancer prevention. The known inhibitory
      effect of NSAIDs on the eicosanoid pathway prompted mechanistic and drug
      development work focusing on cyclooxygenase (COX), culminating in clinical trials
      of cyclooxygenase 2 (COX-2) inhibitors for cancer prevention or treatment.
      However, two COX-2 inhibitors have been withdrawn due to side effects. Here we
      review several pathways of the eicosanoid cascade that are relevant to cancer;
      summarize the evidence regarding the role of COX-2 as a target for cancer
      prevention; and discuss several of the molecular targets that may mediate the
      chemopreventive effect of NSAIDs. The clinically modest results obtained to date
      with COX-2 specific inhibitors used in cancer prevention; the multiple COX-2
      independent targets of both NSAIDs and COX-2 inhibitors; and the limitations of
      some COX-2 inhibitors indicate that exploiting these (non-COX-2) molecular
      targets will likely yield effective new approaches for cancer chemoprevention.

PMID- 15949790
TI  - Susceptibility genes and modifiers for cardiac arrhythmias.
AB  - The last decade has seen a dramatic increase in the understanding of the
      molecular basis of arrhythmias. Much of this new information has been driven by
      genetic studies that focused on rare, monogenic arrhythmia syndromes that were
      accompanied or followed by cellular electrophysiological or biochemical studies.
      The marked clinical heterogeneity known from these familial arrhythmia syndromes
      has led to the development of a multifactorial ("multi-hit") concept of
      arrhythmogenesis in which causal gene mutations have a major effect on disease
      expression that is further modified by other factors such as age, gender,
      sympathetic tone, and environmental triggers. Systematic genetic studies have
      unraveled an unexpected DNA sequence variance in these arrhythmia genes that has
      ethnic-specific patterns. Whether this genetic variance may contribute as a
      second genetic modifier for arrhythmia development is under current
      investigation. The aim of this article is to review common genetic variation in
      ion channel genes and to compare these recent findings.

PMID- 15949791
TI  - The metabolic effects of thia fatty acids in rat liver depend on the position of
      the sulfur atom.
AB  - The effects on oxidation and composition of fatty acids in rat liver were
      compared after administration of fatty acids with sulfur substituted in different
      positions. It has been hypothesized that drugs with hydrophobic backbone have
      lipid-lowering effects because they are not easily catabolized by mitochondrial
      beta-oxidation. Thia fatty acids cannot be beta-oxidized when sulfur is in 3
      position, but beta-oxidation is possible when sulfur is positioned further from
      the carboxyl group. To investigate whether catabolism of thia fatty acids would
      affect their ability to influence lipid metabolism, a series of thia fatty acids
      were synthesized and administered by oral gavage to male Wistar rats (300 mg/kg
      bodyweight/day for 7 days). Depending on the position of the sulfur atom and the
      chain length, the thia fatty acids were beta-oxidized, desaturated and/or
      elongated, and the accumulated amounts were lower as the sulfur atom were
      positioned further from the carboxyl group. All thia fatty acids led to high
      peroxisomal beta-oxidation of endogenous fatty acids, whereas the mitochondrial
      beta-oxidation was high when sulfur was in 3-position, low when sulfur was in 4
      position and similar to controls when sulfur was in 5- or 7-position. The changes
      in hepatic fatty acid composition were more pronounced when sulfur was positioned
      close to the carboxyl group. In conclusion, both the position of the sulfur atom
      and the chain length appear to determine the catabolic fate of thia fatty acids,
      and the non-beta-oxidizable thia fatty acids were most potent in regulating
      oxidation and composition of endogenous fatty acids in rat liver.

PMID- 15949792
TI  - Neuregulin-1 increases the proliferation of neuronal progenitors from embryonic
      neural stem cells.
AB  - Neuregulins are a family of proteins expressed in the developing brain and in
      brain regions that continue to undergo neurogenesis in adult animals. We
      investigated the effects of neuregulins on embryonic neural stem cells (NSCs)
      isolated from E11 mouse telencephalon. Treatment of basic fibroblast growth
      factor (bFGF)-expanded neurosphere cultures with the EGF-like domain of
      neuregulin1-beta1 (NRG-1(177-244)) resulted in a 4-fold increase of
      bromodeoxyuridine (BrDU)-labeled cells, suggesting that NRG-1 stimulated
      proliferation. The majority of the BrdU-positive cells co-labeled with an
      antibody against MAP2, indicating that the proliferating cells were neuronal. No
      BrDU labeling was seen in GFAP- or O4-positive cells. In NRG-1-treated cultures,
      many of the MAP2-positive cells co-labeled with an anti-nestin antibody,
      suggesting that these cells are neuron-restricted progenitors (NRPs). Few
      MAP2/nestin-positive cells were seen in control cultures. The increase in the
      number of neuronal cells in NRG-1-treated cultures was due to increased
      proliferation of MAP2-positive cells rather than the regulation of cell survival
      or fate determination. These results suggest that neuregulins are mitogenic to
      NRPs, thus endogenous neuregulins may play important roles during CNS
      neurogenesis.

PMID- 15949793
TI  - Ephrin-A5 inhibits growth of embryonic sensory neurons.
AB  - EphA-ephrin signaling has recently been implicated in the establishment of motor
      innervation patterns, in particular in determining whether motor axons project
      into dorsal versus ventral nerve trunks in the limb. We investigated whether
      sensory axons, which grow out together with and can be guided by motor axons, are
      also influenced by Eph-ephrin signaling. We show that multiple EphA receptors are
      expressed in DRGs when limb innervation is being established, and EphA receptors
      are present on growth cones of both NGF-dependent (predominantly cutaneous) and
      NT3-dependent (predominantly proprioceptive) afferents. Both soluble and membrane
      attached ephrin-A5 inhibited growth of approximately half of each population of
      sensory axons in vitro. On average, growth cones that collapsed in response to
      soluble ephrin-A5 extended more slowly than those that did not, and ephrin-A5
      significantly slowed the extension of NGF-dependent growth cones that did not
      collapse. Finally, we show that ectopic expression of ephrin-A5 in ovo reduced
      arborization of cutaneous axons in skin on the limb. Together these results
      suggest that sensory neurons respond directly to A-class ephrins in the limb.
      Thus, ephrins appear to pattern sensory axon growth in two ways-both directly,
      and indirectly via their inhibitory effects on neighboring motor axons.

PMID- 15949794
TI  - Comment on 'dynamic mechanical properties of human lenses' by H. A. Weeber et al.
      [Exp. Eye Res. 80 (2005) 425-434].

PMID- 15949795
TI  - The influence of diclofenac ophthalmic solution on the intraocular pressure
      lowering effect of topical 0.5% timolol and 0.005% latanoprost in primary open
      angle glaucoma patients.
AB  - The aim of this randomized, prospective, masked clinical study has been to verify
      the influence of a non-steroidal anti-inflammatory drug ophthalmic solution on
      intraocular pressure reduction induced by 0.5% timolol and 0.005% latanoprost
      eyedrops in patients affected by primary open-angle glaucoma. Thirty-two
      glaucomatous patients, compensated with 0.5% timolol, were randomized into two
      study groups (A and B). Timolol was continued for the first 2 weeks in all
      subjects. On the 15th day, in both groups timolol was replaced by latanoprost,
      and this regimen lasted up to the end of the follow-up (8 weeks). At the
      beginning of the 2nd week of the study, group A additionally started a 5-week
      therapy with topical 0.1% diclofenac; during the same period, group B received
      placebo eyedrops with identical modalities. Intraocular pressure was recorded at
      7-day intervals during the first 7 weeks and at the 10th week. Non-steroidal anti
      inflammatory drug and placebo did not modify the effect of timolol on intraocular
      pressure. In both groups, latanoprost induced a significant decrease in
      intraocular pressure. Diclofenac-treated patients exhibited a marked fall in
      intraocular pressure (p<0.01), whereas in placebo-treated patients, this
      diminution was less noticeable (p<0.05). After diclofenac withdrawal, in group A
      intraocular pressure significantly increased (p<0.01), remaining approximately at
      the same level up to the end of the study. In group B, at the same checks no
      significant variations in intraocular pressure occurred. In primary open-angle
      glaucoma patients, diclofenac significantly enhances the hypotensive effect of
      latanoprost, without influence on timolol efficacy. Because non-steroidal anti
      inflammatory drugs are widely employed in medical practice, supplementary
      ophthalmologic checks should be scheduled during the co-administration of these
      compounds and prostaglandin analogues.

PMID- 15949796
TI  - High-resolution ultrasonography of subretinal structure and assessment of retina
      degeneration in rat.
AB  - The purpose of this work was to evaluate the ability of 80 MHz ultrasonography to
      differentiate intra-retinal layers and quantitatively assess photoreceptor
      dystrophy in small animal models. Four groups of 10 RCS rats each (five
      dystrophic and five controls) were explored at 25, 35, 45 and 55 days post-natal
      (PN). A series of retina cross-sections were obtained ex vivo from outside intact
      eyes using an 80 MHz three-dimensional ultrasound backscatter microscope (20
      microm-axial resolution). Ultrasound features of normal retina were correlated to
      those of corresponding histology and thickness measurements of photoreceptor
      segment and nuclear layers were performed on all groups. To show the ability of
      80 MHz ultrasonography to distinguish the retinal degeneration in vivo, one RCS
      rat was explored at 25 and 55 days post-natal. Ultrasound image of normal retina
      displayed four distinct layers marked by reflections at neurites/nuclei
      interfaces and permitted to differentiate the photoreceptor segment and nuclear
      layers. The backscatter level from the retina was shown to be related to the
      size, density and organization of the intra-layer structure. Ultrasound thickness
      measurements highly correlated with histologic measurements. A thinning (p<0.05)
      of outer nuclear layer (ONL) was detected over time for controls and was thought
      to be assigned to retina maturation. Retinal degeneration started at PN35 and
      resulted in a more pronounced ONL thinning (p<0.05) over time. ONL degeneration
      was accompanied by segment layer thickening (p<0.05) at PN35 and thinning
      thereafter. These changes may indicate accumulation of outer segment debris at
      PN35 then progressive destruction. In vivo images of rat intra-retinal structure
      showed the ability of the method to distinguish the photoreceptor layer changes.
      Our results indicate that 80 MHz ultrasonography reveals intra-retinal layers and
      is sensitive to age and degenerative changes of photoreceptors. This technique
      has great potential to follow-up retinal dystrophy and therapeutic effects in
      vivo.

PMID- 15949797
TI  - In vitro glucose-induced cataract in copper-zinc superoxide dismutase null mice.
AB  - The purpose of this study was to evaluate the involvement of the superoxide
      radical in glucose-induced cataract using lenses from mice lacking the cytosolic
      copper-zinc superoxide dismutase (SOD1). Lenses from wild-type mice and SOD1 null
      mice were kept in organ culture with either 5.6 or 55.6 mM glucose for 6 days.
      The cataract formation was followed with digital image analysis and ocular
      staging. The lens damage was further quantified by analysis of the leakage of
      lactate dehydrogenase into the medium by the uptake of 86Rb and by determining
      the water content of the lenses. The formation of superoxide radicals in the
      lenses was assessed with lucigenin-derived chemiluminescence. Immunohistochemical
      staining for SOD1 was also performed on murine lenses. The SOD1 null lenses
      exposed to high glucose developed more cataract showed an increased leakage of
      lactate dehydrogenase and developed more oedema compared to the control lenses.
      At 5.6 mM glucose there was no difference between the SOD1 null and wild-type
      lenses. Staining for SOD1 was seen primarily in the cortex of the wild-type lens.
      This in vitro model suggests an involvement of the superoxide radical and a
      protective effect of SOD1 in glucose-induced cataract formation.

PMID- 15949798
TI  - Both protein S and Gas6 stimulate outer segment phagocytosis by cultured rat
      retinal pigment epithelial cells.
AB  - Survival of the retina requires the daily phagocytosis of photoreceptor outer
      segments (OS) by the overlying retinal pigment epithelium (RPE). OS phagocytosis
      by cultured RPE requires serum and we have recently shown that the vitamin K
      dependent serum protein, Gas6, can completely replace serum in this process.
      Surprisingly, however, we show here that 4-month-old Gas6 knockout mice have
      normal appearing retinas, except for a reduced ratio of outer segment to inner
      segment length. We also show that removal of Gas6 from serum does not abrogate
      the ability of serum to support OS phagocytosis by rat RPE. Both of these
      findings suggest the presence of an additional serum ligand that is able to
      support OS phagocytosis by RPE cells. Protein S (PS) is a vitamin K-dependent
      serum protein with a high degree of structural similarity to Gas6, and a well
      characterized role in blood coagulation. We report here that recombinant rat PS
      is able to stimulate OS phagocytosis, and similar to Gas6, it does so through a
      Mer-dependent mechanism. This is the first demonstration of a common role for
      Gas6 and PS in any biological process. The existence of redundant ligands for Mer
      dependent OS phagocytosis underscores the critical role of this process in the
      maintenance of retinal function.

PMID- 15949799
TI  - The pig eye as a novel model of glaucoma.
AB  - We validated the pig eye as a model of glaucoma, based on chronic elevation of
      intraocular pressure (IOP). IOP was elevated by cauterising three episcleral
      veins in each of the left eyes of five adult pigs. Right eyes were used as
      controls. Measurement of IOP was performed during the experiment with an
      applanation tonometer (Tono-Pen). Five months after episcleral vein occlusion,
      retinal ganglion cells (RGCs) from both cauterised and control eyes were
      retrogradely backfilled with Fluoro-Gold. Analysis of RGC loss and morphometric
      as characterization of surviving RGCs was performed using whole-mounted retinas.
      Elevation of IOP was apparent after three weeks of episcleral vein cauterisation
      and it remained elevated for at least 21 weeks (duration of the experiments).
      Analysis of RGC loss after chronic elevation of IOP revealed that RGC death was
      significant in the mid-peripheral and peripheral retina, mainly in the temporal
      quadrants of both retinal regions. Moreover the mean soma area of remaining RGCs
      was observed to increase and we found a greater loss of large RGCs in the mid
      peripheral and peripheral retina. We conclude that the pattern of RGC death
      induced in the pig retina by episcleral vein cauterisation resembles that found
      in human glaucoma. On the basis of this study, the pig retina may be considered
      as a suitable model for glaucoma-related studies, based on its similarity with
      human and on its affordability.

PMID- 15949800
TI  - Retinal serotonin, eye growth and myopia development in chick.
AB  - Myopia (short-sightedness) is a visual problem associated with excessive eye
      growth and vitreous chamber expansion. Within the eye serotonin (5
      hydroxytryptamine, 5-HT) appears to have a variety of effects, it alters retinal
      amacrine cell processing, increases intraocular pressure, constricts ocular blood
      vessels, and is also mitogenic. This study sought to determine the role of the
      retinal serotonin system in eye growth regulation. Myopia was produced in 7-day
      old chicks using -15 D spectacle lenses (LIM) and form deprivation (FDM). The
      effect on LIM and FDM of daily intravitreal injections of a combination of 5-HT
      receptor antagonists (1, 10, 50 microM), 5-HT(2) selective antagonist (Mianserin
      0.5, 20 microM) or 5-HT (1, 10, 50 microM) were assessed. Counts were performed
      of serotonin and tyrosine hydroxylase positive neurons and the relative density
      used to account for areal changes due to eye growth. The effect of LIM and lens
      induced hyperopia (LIH) on the numbers of 5-HT-containing amacrine cells in the
      retina were then determined. The combination of 5-HT receptor antagonists
      inhibited LIM by approximately half (1 microM RE: -7.12+/-1.0 D, AL: 0.38+/-0.06
      mm vs. saline RE: -13.19+/-0.65 D, AL: 0.64+/-0.03 mm. RE: p<0.01, AL: p<0.01),
      whereas FDM was not affected (1 microM RE: -8.88+/-1.10 D vs. saline RE: -9.28+/
      1.38 D). The selective antagonist was slightly less effective at inhibiting LIM
      (0.5 microM RE: -9.02+/-1.01 D). These data suggest that serotonin has a
      stimulatory role in LIM, although high doses of serotonin were inhibitory (1
      microM RE: -9.30+/-1.34 D). 5-HT immunoreactivity was localised to a subset of
      amacrine cell bodies in the inner nuclear layer of the retina, and to two
      synaptic strata in the inner plexiform layer. LIM eyes had increased numbers of 5
      HT-containing amacrine cells in the central retina (12.5%). Collectively, these
      results suggest that manipulations to the serotonin system can alter the eye
      growth process but the role of this transmitter system within this process
      remains unclear.

PMID- 15949801
TI  - Structural conservation of residues in BH1 and BH2 domains of Bcl-2 family
      proteins.
AB  - The sequence of Bcl-2 homology domains, BH1 and BH2, is known to be conserved
      among anti- and pro-apoptotic members of Bcl-2 family proteins. But structural
      conservation of these domains with respect to functionally active residues
      playing role in heterodimerization-mediated regulation of apoptosis has never
      been elucidated. Here, we have suggested the formation of an active site by
      structurally conserved residues in BH1 (glycine, arginine) and BH2 (tryptophan)
      domains of Bcl-2 family members, which also accounts for the functional effect of
      known mutations in BH1 (G145A, G145E) and BH2 (W188A) domains of Bcl-2.

PMID- 15949802
TI  - Saccharomyces cerevisiae Pex14p contains two independent Pex5p binding sites,
      which are both essential for PTS1 protein import.
AB  - Pex14p is a peroxisomal membrane-associated protein involved in docking of both
      Pex5p and Pex7p to the peroxisomal membrane. Previous studies have shown that, in
      humans, the N-terminal region of Pex14p interacts with WxxxF/Y motifs in Pex5p.
      Here, we report that Saccharomyces cerevisiae Pex14p contains two independent
      Pex5p binding sites, one in the N- and one in the C-terminus. Using deletion
      analysis we show that, in vivo, both of these interactions are needed for PTS1
      import. Furthermore, we show that the characterized WxxxF/Y motifs of Pex5p are
      not essential for binding to the N-terminus of Pex14p but do play a role in the
      interaction with the Pex14 C-terminus. Thus, the data suggest that the mechanism
      of the Pex14p-Pex5p interaction in yeast is different from that previously
      reported for humans.

PMID- 15949803
TI  - Characterization and comparative analysis of Arabidopsis phosphatidylinositol
      phosphate 5-kinase 10 reveals differences in Arabidopsis and human
      phosphatidylinositol phosphate kinases.
AB  - Arabidopsis phosphatidylinositol phosphate (PtdInsP) kinase 10 (AtPIPK10;
      At4g01190) is shown to be a functional enzyme of the subfamily A, type I
      AtPtdInsP kinases. It is biochemically distinct from AtPIPK1 (At1g21980), the
      only other previously characterized AtPtdInsP kinase which is of the B subfamily.
      AtPIPK10 has the same K(m), but a 10-fold lower V(max) than AtPIPK1 and it is
      insensitive to phosphatidic acid. AtPIPK10 transcript is most abundant in
      inflorescence stalks and flowers, whereas AtPIPK1 transcript is present in all
      tissues. Comparative analysis of recombinant AtPIPK10 and AtPIPK1 with
      recombinant HsPIPKIalpha reveals that the Arabidopsis enzymes have roughly 200-
      and 20-fold lower V(max)/K(m), respectively. These data reveal one explanation
      for the longstanding mystery of the relatively low phosphatidylinositol-(4,5)
      bisphosphate:phosphatidylinositol-4-phosphate ratio in terrestrial plants.

PMID- 15949804
TI  - Kinetics of inclusion body formation studied in intact cells by FT-IR
      spectroscopy.
AB  - The aggregation of a recombinant lipase as inclusion bodies (IBs) was studied
      directly within intact Escherichia coli cells by FT-IR microspectroscopy. Through
      this approach, it was possible to monitor in real time the different kinetics of
      IB formation at 37 and 27 degrees C, in excellent agreement with the results of
      the SDS-PAGE analysis. Furthermore, insights on the residual native-like
      structure of the expressed protein within IB--both isolated and inside cells-
      were obtained by the secondary structure analysis of the Amide I band in the IB
      FT-IR spectra.

PMID- 15949805
TI  - Grifolin, a potential antitumor natural product from the mushroom Albatrellus
      confluens, inhibits tumor cell growth by inducing apoptosis in vitro.
AB  - Grifolin is a natural biologically active substance isolated from the fresh
      fruiting bodies of the mushroom Albatrellus confluens. Here, for the first time,
      we describe a novel activity of grifolin, namely its ability to inhibit the
      growth of tumor cells by the induction of apoptosis. Grifolin strongly inhibited
      the growth of tumor cell lines: CNE1, HeLa, MCF7, SW480, K562, Raji and B95-8.
      Analysis of acridine orange (AO)/ethidium bromide (EB) staining and flow
      cytometry showed that grifolin possessed apoptosis induction activity to CNE1,
      HeLa, MCF7 and SW480. Furthermore, the cytochrome c release from mitochondria was
      detected by confocal microscopy in CNE1 cells after a 12h treatment with
      grifolin. The increase of caspase-8, 9, 3 activities revealed that caspase was a
      key mediator of the apoptotic pathway induced by grifolin, and the
      underexpression of Bcl-2 and up-regulation of Bax resulted in the increase of
      Bax: Bcl-2 ratio, suggesting that Bcl-2 family involved in the control of
      apoptosis. Owing to the combination of the significant antitumor activity by
      inducing apoptosis and natural abundance of the compound, grifolin holds the
      promise of being an interesting antitumor agent that deserves further laboratory
      and in vivo exploration.

PMID- 15949806
TI  - Prediction of protein subcellular location using a combined feature of sequence.
AB  - To understand the structure and function of a protein, an important task is to
      know where it occurs in the cell. Thus, a computational method for properly
      predicting the subcellular location of proteins would be significant in
      interpreting the original data produced by the large-scale genome sequencing
      projects. The present work tries to explore an effective method for extracting
      features from protein primary sequence and find a novel measurement of similarity
      among proteins for classifying a protein to its proper subcellular location. We
      considered four locations in eukaryotic cells and three locations in prokaryotic
      cells, which have been investigated by several groups in the past. A combined
      feature of primary sequence defined as a 430D (dimensional) vector was utilized
      to represent a protein, including 20 amino acid compositions, 400 dipeptide
      compositions and 10 physicochemical properties. To evaluate the prediction
      performance of this encoding scheme, a jackknife test based on nearest neighbor
      algorithm was employed. The prediction accuracies for cytoplasmic, extracellular,
      mitochondrial, and nuclear proteins in the former dataset were 86.3%, 89.2%,
      73.5% and 89.4%, respectively, and the total prediction accuracy reached 86.3%.
      As for the prediction accuracies of cytoplasmic, extracellular, and periplasmic
      proteins in the latter dataset, the prediction accuracies were 97.4%, 86.0%, and
      79.7, respectively, and the total prediction accuracy of 92.5% was achieved. The
      results indicate that this method outperforms some existing approaches based on
      amino acid composition or amino acid composition and dipeptide composition.

PMID- 15949807
TI  - Zinc in lipase L1 from Geobacillus stearothermophilus L1 and structural
      implications on thermal stability.
AB  - Lipase L1 from Geobacillus stearothermophilus L1 contains an unusual extra
      domain, making a tight intramolecular interaction with the main catalytic domain
      through a Zn2+-binding coordination. To elucidate the role of the Zn2+, we
      disrupted the Zn2+-binding site by mutating the zinc-ligand residues (H87A,
      D61A/H87A, and D61A/H81A/H87A/D238A). The activity vs. temperature profiles of
      the mutant enzymes showed that the disruption of the Zn2+-binding site resulted
      in a notable decrease in the optimal temperature for maximal activity from 60 to
      45-50 degrees C. The mutations also abolished the Zn2+-induced thermal
      stabilization. The wild-type enzyme revealed a 34.6-fold increase in
      stabilization with the addition of Zn2+ at 60 degrees C, whereas the mutant
      enzymes exhibited no response to Zn2+. Additional circular dichroism spectroscopy
      studies also confirmed the structural stabilizing role of Zn2+ on lipase L1 at
      elevated temperatures.

PMID- 15949809
TI  - Synthesis of submicrometer-sized titania spherical particles with a sol-gel
      method and their application to colloidal photonic crystals.
AB  - A synthetic method for preparing submicrometer-sized titania particles is
      proposed, which is based on hydrolysis of titanium alkoxide with the use of a
      cosolvent and an amine catalyst for alkoxide hydrolysis. The preparation was
      performed with different amines of ammonia, methylamine (MA), and dimethylamine
      (DMA) in different solvents of ethanol/acetonitrile, ethanol/methanol,
      ethanol/acetone, ethanol/acetonitrile, and ethanol/formamide for 0.1-0.3 M water
      and 0.03 M titanium tetraisopropoxide (TTIP) at temperatures of 10-50 degrees C.
      The use of the ethanol/acetonitrile solvent with MA was required for preparing
      monodispersed, spherical particles. The number average of the titania particle
      sizes and their coefficient of variation were varied from 143 to 551 nm and from
      5.7 to 20.6%, respectively, with reaction temperature and concentrations of water
      and MA. Colloidal crystals of titania particles fabricated with a sedimentation
      method revealed reflection peaks attributed to Bragg's diffraction. Annealing at
      100-1000 degrees C led to shrinkage and crystallization of titania particles
      followed by an increase in the refractive index of titania particles.

PMID- 15949808
TI  - NOR-1 is involved in VEGF-induced endothelial cell growth.
AB  - Neuron-derived orphan receptor-1 (NOR-1) is a transcription factor over-expressed
      in human atherosclerotic plaques that is involved in vascular smooth muscle cell
      proliferation. The aim of this study was to analyze whether NOR-1 plays a role in
      vascular endothelial growth factor (VEGF) induced endothelial cell growth. VEGF
      induced an early and transient up-regulation of NOR-1 in human umbilical vein
      endothelial cells (HUVEC). NOR-1 up-regulation by VEGF is processed through VEGF
      receptor-2 (VEGFR-2) and involves different signaling pathways including increase
      in cytosolic Ca(2+), activation of protein kinase C and mitogen-activated protein
      kinase (MAPK) pathways (both extracellular-signaling regulated kinase [ERK] and
      p38 MAPK). VEGF induced CREB activation (phosphorylation in Ser(133)). In
      transfection assays, a dominant-negative of CREB inhibited NOR-1 promoter
      activity, while mutation of the three CRE sites in the NOR-1 promoter abolished
      VEGF-induced NOR-1 promoter activity. Antisense oligonucleotides against NOR-1
      inhibited VEGF-induced endothelial cell growth (reduced DNA synthesis, and
      inhibited cell cycle progression and endothelial cell wound repair after
      mechanical injury). These results indicate that NOR-1 could be a key
      transcription factor regulating endothelial cell growth induced by VEGF.

PMID- 15949810
TI  - Stability of mixtures of charged silica, silica-alumina, and magnetite colloids.
AB  - We report experiments on the stability of aqueous mixtures of charged colloidal
      magnetite and charged silica and silica covered with alumina particles of similar
      size. First, positively charged magnetite dispersions were mixed with negatively
      charged silica dispersions at pH 4, at different volume ratios and low colloid
      volume fractions, producing mixtures which were stable over a period of weeks
      despite the expected electrostatic attraction between the oppositely charged
      particles. When magnetite particles were mixed with positively charged silica
      covered with alumina at pH 4 under exactly the same conditions, some of the
      systems separated to form a magnetite sediment. When the volume fraction of the
      initial dispersions was increased, the behavior of the mixtures was the opposite:
      positive magnetite/negative silica mixtures were unstable at intermediate volume
      ratios. The unexpected behavior of the mixtures was investigated by means of
      electrophoretic mobility, initial susceptibility, and dynamic light scattering
      measurements as well as sedimentation experiments.

PMID- 15949811
TI  - The inflammatory response in the mouse stomach to Helicobacter bizzozeronii,
      Helicobacter salomonis and two Helicobacter felis Strains.
AB  - The inflammatory response in the mouse stomach was evaluated as a means of
      distinguishing different non-pylori Helicobacter (H.) strains in terms of
      virulence. Mice of four strains (BALB/c, SJL, C57BL/6 and CFW) were infected
      intragastrically with four bacterial strains (H. felis ATCC 49179 and CCUG 37471,
      H. bizzozeronii and H. salomonis). The animals were killed for gastric
      examination at 3, 9 or 16 weeks post-inoculation. H. salomonis could not be
      detected by the polymerase chain reaction, but the other three organisms were
      detected in all stomach samples at all timepoints. SJL mice consistently showed
      particularly severe gastric inflammation regardless of bacterial strain.
      Lymphocytes and occasionally neutrophils were seen in submucosa and lamina
      propria mucosae. BALB/c mice showed the least severe inflammatory changes. H.
      bizzozeronii differed from the two H. felis strains in producing less striking
      pathological changes in mice. Of the two H. felis strains, ATCC 49179 produced
      the more severe inflammatory changes in SJL mice.

PMID- 15949812
TI  - Vitellogenesis inhibition in Oncopeltus fasciatus females (Heteroptera:
      Lygaeidae) exposed to cadmium.
AB  - Newly moulted females of the insect Oncopeltus fasciatus were exposed to cadmium
      (Cd) dissolved in the drinking water (50-400 mg l(-1) Cd) for 5 days. Cd exposure
      delayed ovarian maturation and inhibited egg production. Exposure to Cd,
      moreover, decreased hemolymph levels of the two major vitellogenin polypeptides
      of O. fasciatus, VG1 and VG2, in a concentration-dependent way, probably by a
      reduction in their synthesis. The ovarian levels of VG1 and VG2 were also
      decreased in Cd-exposed females. It was next investigated whether Cd effects
      might be a consequence of the endocrine disruption of vitellogenin synthesis,
      which is controlled by juvenile hormone (JH). JH replacement therapy did not
      restore VG1 or VG2 levels in Cd-exposed females, but did so in starved females.
      Our results do not therefore support a disturbance of JH production or a
      reduction in feeding as the cause of the reduced vitellogenin polypeptide levels,
      but rather point to the site of action of JH, the JH receptor, as the target of
      Cd effects.

PMID- 15949813
TI  - Gene expression changes in Ephestia kuehniella caterpillars after parasitization
      by the endoparasitic wasp Venturia canescens analyzed through cDNA-AFLPs.
AB  - To understand the transcriptional response of Ephestia kuehniella caterpillars to
      parasitization by the endoparasitic wasp Venturia canescens, we examined patterns
      of gene expression in parasitized and unparasitized host caterpillars using the
      cDNA-AFLP (cDNA-amplified fragment length polymorphism) technique. Among the
      approximately 1860 cDNA-fragments detected by using 88 different AFLP primer
      combinations, we identified 13 transcripts in parasitized caterpillars that
      showed a suppressed expression pattern with cDNA-AFLP results being confirmed by
      virtual Northern blot or RT-PCR analysis. Apparently, two different wasp
      genotypes (RP, RM) seem to differ in their ability to regulate host physiology
      with regard to suppression of certain genes. Sequence analysis of the cDNA
      fragments revealed that some of the respective genes are likely to be involved in
      energy metabolism, protein synthesis, or in signal transduction. In addition, one
      sequence corresponds to a gene encoding the lepidopteran silk protein fibroin.
      The putative function of these genes in the interactions between endoparasitoids
      and their host insects is discussed.

PMID- 15949814
TI  - An in vitro study on regulation of prothoracic gland activity in the early last
      larval instar of the silkworm Bombyx mori.
AB  - The endocrine mechanisms that regulate prothoracic gland (PG) activity in early
      stages of final larval instar of the silkworm Bombyx mori were investigated using
      a newly developed long-term cultivation system of the gland. The PGs dissected
      from day-0 fifth instar larvae did not secrete detectable amounts of ecdysone for
      the first 24 h in culture but started secretion within the next 2 days. The
      amount of secreted ecdysone increased day by day. When day-0 PGs were co
      cultivated with corpora allata, however, they remained inactive for at least 8
      days. PGs dissected from 1-day younger larvae (day-3 fourth instar larvae)
      secreted ecdysone for the first 24 h but stopped secretion for the next 24 h,
      followed by recovery of ecdysone secretory activity. By contrast, PGs from day-1
      fourth instar larvae remained active throughout a cultivation period without any
      sign of inactivation. However, when the same glands were exposed to a high titer
      of 20-hydroxyecdysone for the second 24h in culture, they gradually lost their
      activity. These results indicate that PGs of fourth instar larvae are inactivated
      by ecdysteroid through a negative feedback mechanism and that thus inactivated
      PGs spontaneously recover ecdysone secretory activity in the early fifth instar
      unless inhibited by juvenile hormone.

PMID- 15949815
TI  - Extended and flexible domain solution structure of the extracellular matrix
      protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and
      constrained modelling.
AB  - Kallmann's syndrome corresponds to a loss of sense of smell and hypogonadotrophic
      hypogonadism. Defects in anosmin-1 result in the X-linked inherited form of
      Kallmann's syndrome. Anosmin-1 is an extracellular matrix protein comprised of an
      N-terminal, cysteine-rich (Cys-box) domain and a whey acidic protein-like (WAP)
      domain, followed by four fibronectin type III (FnIII) domains. The solution
      structures of recombinant proteins containing the first three domains (PIWF1) and
      all six domains (PIWF4) were determined by X-ray scattering and analytical
      ultracentrifugation. Guinier analyses showed that PIWF1 and PIWF4 have different
      radii of gyration (R(G)) values of 3.1 nm and 6.7 nm, respectively, but similar
      cross-sectional radii of gyration (R(XS)) values of 1.5 nm and 1.9 nm,
      respectively. Distance distribution functions showed that the maximum lengths of
      PIWF1 and PIWF4 were 11 nm and 23 nm, respectively. Analytical
      ultracentrifugation gave sedimentation coefficients of 2.52 S and 3.55 S for
      PIWF1 and PIWF4, respectively. The interpretation of the scattering data by
      constrained modelling requires homology models for all six domains in anosmin-1.
      While models were already available for the WAP and FnIII domains, searches
      suggested the Cys-box domain may resemble the cysteine-rich region of the insulin
      like growth factor receptor. Automated constrained molecular modelling based on
      joining the anosmin-1 domains with structurally randomised linkers resulted in
      10,000 models for anosmin-1. A trial-and-error search showed that about 0.1-1.4%
      of these models fitted the X-ray data. The best models showed that the three
      domains and six domains in PIWF1 and PIWF4, respectively, were extended. The
      inter-domain linkers in anosmin-1 could not all be extended at the same time, and
      there was evidence for inter-domain flexibility. Models with folded-back domain
      arrangements do not fit the data. These solution structures account for the known
      biological function of anosmin-1, in particular its ability to interact with its
      three macromolecular ligands.

PMID- 15949816
TI  - Hashimoto's encephalopathy: a relapsing form of acute disseminated
      encephalomyelitis.

PMID- 15949817
TI  - A logical circuit for the regulation of fission yeast growth modes.
AB  - Growth of fission yeast at the ends of its cylindrical cells switches from a
      monopolar to a bipolar mode, before it ceases during mitosis and cell division.
      Here we assume that these growth modes correspond to three stable states of an
      underlying regulatory circuit, which is a relatively simple and to a large degree
      autonomous subsystem of an otherwise complex cellular control system. We develop
      a switch-like logical circuit based on three elements defined as binary
      variables. Effects of circuit variables on each other are expressed in terms of
      logical operations. We analyse this circuit for its behavior ("phenotypes") after
      removing single or multiple operations ("mutants"). Known fission yeast polarity
      mutants such as those defective in the switch to bipolar growth can be classified
      based on these predicted 'phenotypes'. Differences in growth patterns between
      daughter cells in different bipolar growth mutants are also predicted by the
      circuit model. The model presented here should provide a useful framework to
      guide future experiments into mechanisms of cellular polarity. This paper
      illustrates the usefulness of simple logical circuits to describe and dissect
      features of complex regulatory processes such as the fission yeast growth
      patterns in both wild type and mutant cells.

PMID- 15949818
TI  - Population dynamics with a stable efficient equilibrium.
AB  - We propose a game-theoretic dynamics of a population of replicating individuals.
      It consists of two parts: the standard replicator one and a migration between two
      different habitats. We consider symmetric two-player games with two
      evolutionarily stable strategies: the efficient one in which the population is in
      a state with a maximal payoff and the risk-dominant one where players are averse
      to risk. We show that for a large range of parameters of our dynamics, even if
      the initial conditions in both habitats are in the basin of attraction of the
      risk-dominant equilibrium (with respect to the standard replication dynamics
      without migration), in the long run most individuals play the efficient strategy.

PMID- 15949820
TI  - Role of lipids and lipid signaling in the development of cannabinoid tolerance.
AB  - Cannabinoid agonists such as Delta9-tetrahydrocannabinol (THC) produce a wide
      range of pharmacological effects both in the central nervous system and in the
      periphery. One of the most striking features of cannabinoids such as THC is the
      magnitude to tolerance that can be produced upon repetitive administration of
      this substance to animals. Relatively modest dosing regimens are capable of
      producing significant tolerance, whereas greater than 100-fold tolerance can be
      obtained with aggressive treatments. While cannabinoid tolerance has been studied
      quite extensively to establish its relevance to the health consequences of
      marijuana use, it has also proven to be a valuable strategy in understanding the
      mechanism of action of cannabinoids. The discovery of the endocannabinoid system
      that contains two receptor subtypes, CB1 and CB2, associated signaling pathways,
      endocannabinoids (anandamide and 2-arachidonoylglycerol) and their synthetic and
      degradative pathways has provided a means of systematically evaluating the
      mechanism of cannabinoid tolerance. It is well known that the CB1 cannabinoid
      receptor is down-regulated in states of cannabinoid tolerance along with
      uncoupling from its second messenger systems. Endocannabinoid levels are also
      altered in selected brain regions during the development of tolerance. While it
      is reasonable to speculate that a likely relationship exists between receptor and
      endocannabinoid levels, at present, little is known regarding the biological
      signal that leads to alterations in endocannabinoid levels. It is also unknown to
      what degree synthetic and degradative pathways for the endocannabinoids are
      altered in states of tolerance. The discovery that the brain is abundant in fatty
      acid amides and glycerols raises the question as to what roles these lipids
      contribute to the endocannabinoid system. Some of these lipids also utilize the
      endocannabinoid metabolic pathways, produce similar pharmacological effects, and
      are capable of modulating the actions of anandamide and 2-arachidonoylglycerol.
      In addition, there are dopamine, glycine, and serotonin conjugates of arachidonic
      acid that may also contribute to the actions of endocannabinoids. A systematic
      examination of these lipids in cannabinoid tolerance might shed light on their
      physiological relevance to the endocannabinoid system.

PMID- 15949819
TI  - N-acylphosphatidylethanolamine-hydrolyzing phospholipase D: a novel enzyme of the
      beta-lactamase fold family releasing anandamide and other N-acylethanolamines.
AB  - N-acylethanolamines (NAEs) are a lipid class present in brain and other animal
      tissues and contains anandamide (an endocannabinoid) and other bioactive
      substances. NAEs are formed from N-acylphosphatidylethanolamines (NAPEs) by a
      phospholipase D (PLD)-type enzyme abbreviated to NAPE-PLD. Although this enzyme
      has been recognized for more than 20 years, its molecular cloning has only
      recently been achieved by us. We highly purified NAPE-PLD from the particulate
      fraction of rat heart, and on the basis of peptide sequences with the purified
      enzyme cloned its cDNA from mouse, rat and human. The deduced primary structures
      revealed no homology with any PLDs so far reported, but was suggested to belong
      to the beta-lactamase fold family. When overexpressed in COS-7 cells, the NAPE
      PLD activity increased about 1000-fold in comparison with the endogenous
      activity. The recombinant enzyme generated various long-chain NAEs including
      anandamide from their corresponding NAPEs at similar rates. However, the enzyme
      was inactive with phosphatidylethanolamine and phosphatidylcholine and did not
      catalyze transphosphatidylation, a reaction characteristic of PLD. The enzyme was
      widely expressed in murine organs with higher levels in brain, testis and kidney.
      The existence of NAPE-PLD specifically hydrolyzing NAPEs to NAEs emphasizes
      physiological significance of NAEs including anandamide in brain and other
      tissues.

PMID- 15949821
TI  - Heavy metals accumulation in two syntopic sandhopper species: Talitrus saltator
      (Montagu) and Talorchestia ugolinii Bellan Santini and Ruffo.
AB  - We assessed the capacity for heavy metals accumulation in Talorchestia ugolinii
      by standard methods of heavy metals analysis. To compare the bioaccumulation in
      syntopic sandhopper species, we collected samples of T. ugolinii and Talitrus
      saltator living on the same and on different beaches in Corsica. There was a
      marked difference in the zonal distribution of the two species along the sea-land
      axis of the beach: T. ugolinii was distributed nearer the water line than T.
      saltator. The bioaccumulation capacity of T. ugolinii only partly matched that of
      the Mediterranean T. saltator: while Hg, Zn, Cu, and Cd were accumulated by both
      species, Al and Fe were accumulated by T. saltator but not by T. ugolinii. Pb was
      accumulated only by T. ugolinii, while Cr did not seem to be accumulated by
      either species. The bioaccumulation in sympatric T. saltator and T. ugolinii
      specimens collected on the same beach reflected the general trend of the two
      species on the Tyrrhenian and Corsican coasts, respectively. Moreover, six of the
      eight heavy metals considered (Hg, Pb, Zn, Fe, Al, Cu) were present in higher
      quantities in T. ugolinii than in T. saltator, independently of whether the trace
      elements were accumulated by the two species. Thus, there are some differences
      between T. ugolinii and T. saltator, even when the two species live in the same
      locality. These differences involve their zonation within the damp belt of sand,
      the bioaccumulation of some heavy metals (Al, Pb, Fe), and the quantity of each
      heavy metal in the body, independent of the bioaccumulation capacity.

PMID- 15949822
TI  - Transcription-coupled repair: impact on UV-induced mutagenesis in cultured rodent
      cells and mouse skin tumors.
AB  - UV-induced cyclobutane pyrimidine dimers (CPDs) are removed with accelerated
      speed from the transcribed strand of expressed genes in cultured mammalian cells
      by a process called transcription-coupled repair (TCR). It has been previously
      shown that this phenomenon has consequences for the molecular nature of the
      mutations induced by UV-light. Here, we review these data and show that TCR has
      not only a clear impact on UV-induced mutations in cultured mammalian cells but
      also on genes involved in tumor formation in the skin of UV-exposed mice.
      Mutations observed in the p53 gene in UV-induced squamous cell carcinoma are
      predominantly found at sites of dipyrimidines in the non-transcribed strand. In
      contrast, in UVC-irradiated Csb(-/-) Chinese hamster cells and in UVB-induced
      tumors in the Csb(-/-) mouse, almost all mutations are at positions of
      dipyrimidine sites in the transcribed strand of the mutated gene. Csb(-/-) mice
      appear to be susceptible to UVB-induced skin cancer in contrast to the human CSB
      patients. We speculate that the UVB-induced cancer susceptibility of Csb(-/-)
      mice is related to the absence of TCR as well as to a lack of a compensating
      global genome repair system for CPDs in mice.

PMID- 15949823
TI  - Cannabinoids augment the release of neuropeptide Y in the rat hypothalamus.
AB  - Little is known about the mechanism of action behind the orexigenic activity of
      cannabinoids. Neuropeptide Y (NPY) is one of the most potent orexigenic factors
      and is a key mediator in the hypothalamic control of food intake. We examined the
      effect of cannabinoids on NPY release using a rat hypothalamic explant model. The
      cannabinoid agonists anandamide (AEA) and CP55,940 both significantly augmented
      resting and KCl-evoked NPY release. AM251, a cannabinoid receptor antagonist,
      blocked the augmentation of NPY release elicited by AEA and CP55,940.
      Additionally, AM251 administered alone, in the absence of exogenous cannabinoid
      agonists, inhibited NPY release demonstrating the role of endogenous cannabinoids
      in NPY release. Combined, these findings demonstrate that cannabinoids augment
      NPY release in the hypothalamus and that this may be a potential mechanism behind
      the orexigenic activity of cannabinoids.

PMID- 15949824
TI  - How rainfall, relative humidity and temperature influence volatile emissions from
      apple trees in situ.
AB  - Headspace volatiles from apple-bearing twigs were collected in the field with a
      Radiello sampler during three different diurnal periods over the complete fruit
      growing season. Analyses by thermal desorption-GC-MS identified a total of 62
      compounds in changing quantities, including the terpenoids alpha-pinene,
      camphene, beta-pinene, limonene, beta-caryophyllene and (E,E)-alpha-farnesene,
      the aldehydes (E)-2-hexenal, benzaldehyde and nonanal, and the alcohol (Z)-3
      hexen-1-ol. The variations in emission of these plant odours were statistically
      related to temperature, humidity and rainfall in the field. Remarkably, rainfall
      had a significant positive influence on changes in volatile release during all
      three diurnal periods, and further factors of significance were temperature and
      relative humidity around noon, relative humidity in the late afternoon, and
      temperature and relative humidity during the night. Rainfall was associated
      consistently with an increase in the late afternoon in terpene and aldehyde
      volatiles with a known repellent effect on the codling moth, one of the key pests
      of apple fruit. During the summer of 2003, a season characterized by below
      average rainfall, some postulated effects of drought on trees were tested by
      establishing correlations with rainfall. Emissions of the wood terpenes alpha
      pinene, beta-pinene and limonene were negatively correlated with rainfall.
      Another monoterpene, camphene, was only detected in this summer but not in the
      previous years, and its emissions were negatively correlated with rainfall,
      further supporting the theory that drought can result in higher formation of
      secondary metabolites. Finally, the two green leaf volatiles (E)-2-hexenal and
      (Z)-3-hexen-1-ol were negatively correlated with rainfall, coinciding well with
      the expectation that water deficit stress increases activity of lipoxygenase. To
      our knowledge, this work represents the first empirical study concerning the
      influence of abiotic factors on volatile emissions from apple trees in situ.

PMID- 15949825
TI  - Xanthomicrol is the main cytotoxic component of Dracocephalum kotschyii and a
      potential anti-cancer agent.
AB  - Spinal-Z, a methanolic mixture of dried powdered seeds of Peganum harmala Linn.
      and leaf of Dracocephalum kotschyii Boiss. is an Iranian ethno-medical remedy. It
      has been used for the treatment of various types of cancer for many years. To
      evaluate the use of Spinal-Z in treatment of cancer, we examined its effects
      against a panel of malignant cell lines and tumors induced in mice. The in vitro
      antiproliferative activities of Spinal-Z, the seed extract of P. harmala and the
      leaf extract of D. kotschyii were determined using the MTT assay. The
      concentration of the agent required to inhibit cell growth by 50% (IC50) was
      estimated. In addition, the anti-tumor activities of the remedy and its
      constituents were investigated. Viability of cells treated with Spinal-Z and its
      components decreased in a dose dependent manner. Spinal-Z and its components
      showed cytotoxic effects against all cell lines tested. The leaf extract of D.
      kotschyii showed a greater preferential cytotoxic effect than the seed extract of
      P. harmala and Spinal-Z, on all cell lines tested. Harmine showed cytotoxicity
      against HL60 and K562 cell lines. This could explain the cytotoxic effect of P.
      harmala on these cells. The leaf extract of D. kotschyii was able to inhibit
      tumor proliferation in mice. The active ingredient in the leaf extract of D.
      kotschyii appears to be a flavone identified as xanthomicrol. Xanthomicrol was
      able to inhibit proliferation of a number of malignant cells. The cytotoxic
      effects of xanthomicrol were more selective towards malignant cells than
      doxorubicin.

PMID- 15949826
TI  - Pinoresinol-lariciresinol reductases with different stereospecificity from Linum
      album and Linum usitatissimum.
AB  - Recently it was found that cell cultures and plants of Linum species contain
      lignans of various chemical structures. The stereochemistry of these compounds
      differ among species. Cell cultures of L. album accumulate (-)-podophyllotoxin
      together with pure (-)-secoisolariciresinol. The presence of both enantiomers of
      the precursor pinoresinol indicates that in L. album cell cultures the reactions
      from pinoresinol to secoisolariciresinol are the first steps determining
      enantiospecificity in biosynthesis of podophyllotoxin. Seeds of L. usitatissimum
      contain almost enantiomerically pure (+)-secoisolariciresinoldiglucosid derived
      from (+)-secoisolariciresinol. A cell culture of this species contains a mixture
      of both enantiomers of pinoresinol and pure (+)-secoisolariciresinol. In order to
      get more insight into the mechanism of (-)- and (+)-secoisolariciresinol
      biosynthesis, respectively, we isolated a cDNA encoding pinoresinol-lariciresinol
      reductase (PLR) from L. album. The heterologously expressed PLR-La1 converts only
      (+)-pinoresinol into (-)-secoisolariciresinol. In contrast, the heterologously
      expressed PLR from L. usitatissimum converts only (-)-pinoresinol to (+)
      secoisolariciresinol confirming the results from others. Comparison of all
      available PLR protein sequences resulted in a few amino acids which may be
      responsible for the action of the PLRs with respect to the different
      enantioselectivity. A mutagenesis approach could not confirm this hypothesis.
      Aspects about the evolution of PLRs are discussed.

PMID- 15949828
TI  - ent-Kauranoid derivatives from Sideritis moorei.
AB  - Seven new ent-kauranoid derivatives ent-7alpha,18-dihydroxykaur-16-en-3-one, ent
      18-acetoxy-3beta,7alpha-dihydroxykaur-15-en-17-al, ent-3beta-acetoxy-7alpha,18
      dihydroxykaur-15-en-17-al, ent-18-acetoxy-3beta,7alpha,17-trihydroxykaur-15-ene,
      ent-3beta-acetoxy-7alpha,17,18-trihydroxykaur-15-ene, ent-18-acetoxy
      3beta,7alpha,17-trihydroxy-15beta,16beta-epoxykaurane and ent-3beta-acetoxy
      7alpha,17,18-trihydroxy-15beta,16beta-epoxykaurane have been isolated from
      Sideritis moorei. The structures of these compounds have been established by
      spectroscopic means and chemical correlations.

PMID- 15949827
TI  - Molecular and biochemical characterisation of a serine acetyltransferase of
      onion, Allium cepa (L.).
AB  - We have previously cloned a cDNA, designated SAT1, corresponding to a gene coding
      for a serine acetyltransferase (SAT) from onion (Allium cepa L.). The SAT1 locus
      was mapped to chromosome 7 of onion using a single-stranded conformation
      polymorphism (SSCP) in the 3' UTR of the gene. Northern analysis has demonstrated
      that expression of the SAT1 gene is induced in leaf tissue in response to low S
      supply. Phylogenetic analysis has placed SAT1 in a strongly supported group (100%
      bootstrap) that comprises sequences that have been characterised biochemically,
      including Allium tuberosum, Spinacea oleracea, Glycine max, Citrullus vulgaris,
      and SAT5 (AT5g56760) of Arabidopsis thaliana. This group can be divided further
      with the SAT1 of A. cepa sequence grouping strongly with the A. tuberosum
      sequence. Translation of SAT1 from onion generates a protein of 289 amino acids
      with a calculated molecular mass of 30,573 Da and pI of 6.52. The conserved G277
      and H282 residues that have been identified as critical for L-cysteine inhibition
      are observed at G272 and H277. SAT1 has been cloned into the pGEX plasmid,
      expressed in E. coli and SAT activity of the recombinant enzyme has been measured
      as acetyl-CoA hydrolysis detected at 232 nm. A Km of 0.72 mM was determined for l
      serine as substrate, a Km of 92 microM was calculated with acetyl-CoA as
      substrate, and an inhibition curve for L-cysteine generated an IC50 value of 3.1
      microM. Antibodies raised against the recombinant SAT1 protein recognised a
      protein of ca. 33 kDa in whole leaf onion extracts. These properties of the SAT1
      enzyme from onion are compared with other SAT enzymes characterised from closely
      related species.

PMID- 15949829
TI  - Assessment of sociodemographic factors and socio-economic status affecting the
      coverage of compulsory and private immunization services in Istanbul, Turkey.
AB  - OBJECTIVES: The primary objective of this study was to determine the coverage of
      the Expanded Programme of Immunization (EPI) of the Ministry of Health and the
      coverage of private vaccines in the Umraniye Health District in order to
      establish approaches for improving vaccination services. Other objectives were to
      define the areas that present higher risks for non-vaccination and to determine
      the factors that influence vaccination coverage. METHODS: A '30 x 7' cluster
      sampling design was adopted as the sampling method. Thirty streets were selected
      at random from each health care region. Sociodemographic and socio-economic
      characteristics of the population, utilization of vaccination services and
      vaccination status of children under the age of 5 years were determined by face
      to-face interviews. Odds ratios for the sociodemographic and socio-economic
      characteristics, health centre region and inner country immigration were assessed
      as possible related factors with the vaccination coverage rates for children
      under 5 years and under 1 year using the backward elimination method in logistic
      regression. RESULTS: Vaccination coverage was as follows: hepatitis B third dose,
      84.6%; Bacille Calmette-Guerin, 94.8%; diphtheria, tetanus, pertussis (DPT) third
      dose, 90.1%; oral polio virus (OPV) third dose, 90.0%; measles, 88.7%; DPT
      booster dose, 79.1%; OPV booster dose, 79.0%; measles, mumps, rubella (MMR),
      13.3%; haemophilus influenza type b (Hib), 9.3%; and Varicella vaccine, 3.3%. The
      full vaccination rates for children under 5 years and under 1 year were 68.3 and
      79.5%, respectively. Higher socio-economic status was associated with a higher
      rate of full vaccination and private vaccination for children under 5 years of
      age. CONCLUSIONS: Full vaccination rates for children aged less than 1 year and
      less than 5 years were higher in our district than in Istanbul. However, we did
      not meet the EPI aims for any of the vaccines, and differences were observed in
      vaccination coverage rates between different socio-economic groups in the
      district. Therefore, an intervention programme should be considered to achieve
      the EPI's goals, particularly in socio-economically disadvantaged groups. Also,
      the coverage of private vaccination (MMR, Hib, Varicella) is low and more
      children from higher socio-economic groups receive these vaccines.

PMID- 15949830
TI  - The influence of anticoagulants on the measurement of total protein concentration
      in equine peritoneal fluid.
AB  - The aim of this study was to evaluate the influence of two commonly used
      anticoagulants (K3EDTA and lithium heparin) on refractometric and
      spectrophotometric measurement of total protein (TP) concentration in equine
      peritoneal fluid samples. The influence of a commercial solution of K3EDTA, a
      solution of K3EDTA in distilled water and lithium heparin on the refractometric
      and spectrophotometric (biuret) quantification of TP content in peritoneal fluid
      samples was assessed. Total protein concentration measured by refractometry was
      consistently overestimated in samples with commercial K3EDTA. The solution of
      K3EDTA in distilled water only caused TP overestimation at high K3EDTA
      concentrations (>5 micromol/ml). By contrast, lithium heparin did not influence
      the refractometric values of TP. Neither anticoagulant modified TP values when
      measured by the biuret method. In conclusion, the use of K3EDTA as anticoagulant
      may result in a significant overestimation of TP values of peritoneal fluid
      samples measured by refractometry.

PMID- 15949831
TI  - Periodic dynamics in a two-stage Allee effect model are driven by tension between
      stage equilibria.
AB  - Single species difference population models can show complex dynamics such as
      periodicity and chaos under certain circumstances, but usually only when rates of
      intrinsic population growth or other life history parameter are unrealistically
      high. Single species models with Allee effects (positive density dependence at
      low density) have also been shown to exhibit complex dynamics when combined with
      over-compensatory density dependence or a narrow fertility window. Here we
      present a simple two-stage model with Allee effects which shows large amplitude
      periodic fluctuations for some initial conditions, without these requirements.
      Periodicity arises out of a tension between the critical equilibrium of each
      stage, i.e. when the initial population vector is such that the adult stage is
      above the critical value, while the juvenile stage is below the critical value.
      Within this area of parameter space, the range of initial conditions giving rise
      to periodic dynamics is driven mainly by adult mortality rates. Periodic dynamics
      become more important as adult mortality increases up to a certain point, after
      which periodic dynamics are replaced by extinction. This model has more realistic
      life history parameter values than most 'chaotic' models. Conditions for periodic
      dynamics might arise in some marine species which are exploited (high adult
      mortality) leading to recruitment limitation (low juvenile density) and might be
      an additional source of extinction risk.

PMID- 15949832
TI  - 7-Alkylguanine adduct levels in urine, lungs and liver of mice exposed to styrene
      by inhalation.
AB  - This study describes urinary excretion of two nucleobase adducts derived from
      styrene 7,8-oxide (SO), i.e., 7-(2-hydroxy-1-phenylethyl)guanine (N7alphaG) and 7
      (2-hydroxy-2-phenylethyl)guanine (N7betaG), as well as a formation of N7-SO
      guanine adducts in lungs and liver of two month old male NMRI mice exposed to
      styrene by inhalation in a 3-week subacute study. Strikingly higher excretion of
      both isomeric nucleobase adducts in the first day of exposure was recorded, while
      the daily excretion of nucleobase adducts in following time intervals reached the
      steady-state level at 4.32+1.14 and 6.91+1.17 pmol/animal for lower and higher
      styrene exposure, respectively. beta-SO-guanine DNA adducts in lungs increased
      with exposure in a linear way (F=13.7 for linearity and 0.17 for non-linearity,
      respectively), reaching at the 21st day the level of 23.0 adducts/10(8) normal
      nucleotides, i.e., 0.74 fmol/microg DNA of 7-alkylguanine DNA adducts for the
      concentration of 1500 mg/m3, while no 7-SO-guanine DNA adducts were detected in
      the liver after 21 days of inhalation exposure to both of styrene concentrations.
      A comparison of 7-alkylguanines excreted in urine with 7-SO-guanines in lungs
      (after correction for depurination and for missing alpha-isomers) revealed that
      persisting 7-SO-guanine DNA adducts in lungs account for about 0.5% of the total
      alkylation at N7 of guanine. The total styrene-specific 7-guanine alkylation
      accounts for about 1.0x10(-5)% of the total styrene uptake, while N1-adenine
      alkylation contributes to this percentage only negligibly.

PMID- 15949833
TI  - In vitro effect of the Phoneutria nigriventer spider venom on cell viability,
      paracellular barrier function and transcellular transport in cultured cell lines.
AB  - Phoneutria nigriventer spider venom (PNV) induces, in rats, local edema as result
      of an increased vascular permeability, as well as causes blood-brain barrier
      (BBB) breakdown by altering transendothelial transport routes in hippocampal
      microvessels. In this work we investigated the in vitro effects of PNV on cell
      viability and cellular transport routes using three cell lines, the ECV304
      endothelial-, the C6 glioma- and the MDCK epithelial cells. We showed that PNV
      (14.6 and 292 microg crude venom/ml culture medium) had no direct cytotoxic
      effect on both the ECV304 and the MDCK cell lines but slightly reduced the
      viability of C6 glioma cells (P<0.05) at the highest concentration, as revealed
      by the cellular neutral red uptake assay. The PNV effects on cell transport were
      evaluated in MDCK cell line. PNV seems do not cause any disturbance in the
      paracellular barrier function of the cultured MDCK cells, as shown by the lack of
      a significant change in the distribution and expression of the junctional
      proteins, ZO-1, occludin, E-cadherin and the cytoskeletal F-actin. In contrast,
      PNV-treated MDCK monolayers showed an enhancement in the transepithelial
      electrical resistance and a tendency towards an increased occludin expression. In
      addition, the PNV significantly increased the apical endocytosis of HRP, which
      was not followed by an equivalent exocytosis at the basal side, as revealed by
      biochemical and ultrastructural methods. We conclude that the venom of P.
      nigriventer displays a relatively low cytotoxicity in vitro as well as activates
      directly the endocytic transport pathway in MDCK cells without disrupting the
      paracellular route.

PMID- 15949834
TI  - Peroxidase-mediated oxidative coupling of 1-naphthol: characterization of
      polymerization products.
AB  - The oxidative polymerization of 1-naphthol was investigated in the presence of
      horseradish peroxidase (HRP). Naphthol polymerization products (NPP) were
      characterized for their relative polarity using octanol--water partitioning
      experiments and reverse-phase high pressure liquid chromatography, for structure
      using size exclusion chromatography and liquid chromatography-mass spectrometry
      (LC/MS), and for ecotoxicity using inhibition of bacterial bioluminescence.
      Peroxidase addition resulted in the production of soluble and insoluble NPP.
      Soluble NPP was predominantly more polar than the parent naphthol and comprised
      of trimers and tetramers. Insoluble NPP oligomers included dimers, trimers and
      tetramers. The net aqueous-phase toxicity was significantly reduced due to
      polymer formation and subsequent precipitation. A reaction model deduced from the
      LC/MS fragmentation patterns of trimeric naphthol was proposed for NPP formation.
      Results from this study suggest that HRP-mediated treatment of naphthol
      contaminated soils can achieve risk reduction through (i) the formation of large
      hydrophobic oligomers that are immobilized on the soil matrix; and (ii) reduction
      in aqueous-phase toxicity due to polymer precipitation.

PMID- 15949835
TI  - Evaluation of soil flushing potential for clean-up of desert soil contaminated by
      industrial wastewater.
AB  - The flushing potential of a desert loess soil contaminated by the flame retardant
      Tetrabromobisphenol A (TBBPA), chloride (Cl(-)) and bromide (Br(-)) was studied
      in undisturbed laboratory column experiments (20 cm diameter, 45 cm long) and a
      small field plot (2 x 2 m). While the soluble inorganic ions (Cl(-) and Br(-))
      were efficiently flushed from the soil profile after less than three pore volumes
      (PV) of water, about 50% of the initial amount of TBBPA in the soil was also
      flushed, despite its hydrophobic nature. TBBPA leaching was made possible due to
      a significant increase in the pH of the soil solution from 7.5 to 9, which
      increased TBBPA aqueous solubility. The remaining TBBPA mass in the soil was not
      mobilized from its initial location in the topsoil due to the decrease in pH at
      this horizon. In situ soil flushing demonstrated that this method is a feasible
      treatment for reducing soil contamination at this site.

PMID- 15949836
TI  - Structural effect of the in situ generated titania on its ability to oxidize and
      capture the gas-phase elemental mercury.
AB  - Structural effect of the in situ generated TiO(2) sorbent particle was examined
      for its ability to capture elemental mercury under UV irradiation in a simulated
      combustion flue gas. Titania particles were prepared by thermal gas-phase
      oxidation of Titanium (IV) isopropoxide (TTIP) using a high temperature electric
      furnace reactor. The structural characteristics of the in situ generated TiO(2)
      at various synthesis temperatures were investigated; size distribution and the
      geometric mean diameter were measured using a scanning mobility particle sizer,
      while fractal dimension and radius of gyration were evaluated from the
      transmission electron microscopy images. Results from the Hg(0) capture
      experiment show that with increasing titania synthesis temperature, the overall
      aggregate size increases and the morphology becomes more open-structured to gas
      phase Hg(0) and UV light, resulting in the improved mercury removal capability.

PMID- 15949837
TI  - Hydrodechlorination of dichlorobiphenyls over Ni-Mo/Al2O3 catalysts prepared by
      spray-drying method.
AB  - The hydrodechlorination (HDCl) process of 2,3-, 2,4- and 2,5-dichlorobiphenyls
      was studied over a sulphided Ni-Mo/Al(2)O(3) catalyst in a stirred autoclave at a
      hydrogen pressure of 3 MPa. The catalysts were prepared by spray-drying. They
      were characterized by N(2) adsorption, thermogravimetry and scanning electron
      microscopy with X-ray microanalysis. The reaction temperature of the catalytic
      HDCl process was varied in the range of 230-290 degrees C. Polychlorinated
      biphenyls (PCBs) free transformer oil was used as reaction medium. The HDCl
      degree of dichlorobiphenyl isomers was in the range of 82-93%. The efficiency in
      the chlorine removal was found to be related to the position of the substituted
      chlorine atom and decreased as follows 2,4-dichlorobiphenyl approximately 2,5
      dichlorobiphenyl>2,3-dichlorobiphenyl. For comparison, the HDCl process of 2,3
      dichlorobiphenyl (2,3-PCB) without catalyst was also studied. The chlorine
      removal was 85% for the catalytic HDCl of 2,3-PCB whereas non-catalytic process
      led only to 16% of dechlorination in the same operating conditions, i.e. at 290
      degrees C after 120 min. Monodichlorobiphenyls were not detected in the reaction
      products. The data for both catalytic and non-catalytic conversion of 2,3-PCB fit
      to a first-order model. Kinetic constants and the activation energy of the
      overall HDCl reaction of 2,3-PCB to biphenyl were evaluated. Compared to non
      catalytic process, a nearly threefold decrease in the activation energy was
      observed in the presence of Ni-Mo/Al(2)O(3) catalyst prepared by spray-drying (48
      kJ mol(-1) vs. 124 kJ mol(-1)).

PMID- 15949838
TI  - A review on the usage of POP pesticides in China, with emphasis on DDT loadings
      in human milk.
AB  - This article attempts to review the usage of nine pesticides included in the 12
      Stockholm Convention persistent organic pollutants (POPs) in China and to examine
      the extent of DDT contamination in human milk, focusing on the Chinese
      populations. By comparing all the data available concerning DDTs in human milk
      from 19 countries, it is revealed that the Chinese populations exhibit rather
      high concentrations of DDTs, due to the fact that China has been a major producer
      and consumer of DDTs in the past, and also uses DDT for vector control, resulting
      in higher background levels of DDTs in different ecological compartments. The
      high body loading of DDT in Chinese populations is also related to the high
      dietary intake due to contamination of food. When comparing the data obtained
      recently (1998-2002), the coastal populations such as Guangzhou (DDE+DDT 2.13
      microgg(-1) fat), Hong Kong (2.87 microgg(-1) fat) and Dalian (2.13 microgg(-1)
      fat) contain higher concentrations of DDTs which may reflect the dietary
      difference of consuming more meat and fish, than other Chinese populations
      (Beijing 1.96 microgg(-1) fat; Shenyang 0.87 microgg(-1) fat). In general, the
      rather low ratio of DDE/DDT (e.g., 4.07 for Guangzhou) of the Chinese milk
      samples reflected the more recent releases of DDT. It is recommended to impose a
      tighter control on the use of DDT for vector control as well as for agricultural
      application, conduct regular monitoring of DDT concentrations in different
      ecological compartments which include air, water, sediment and biota. Human milk
      is a preferred indicator reflecting human body loadings of POPs including DDTs,
      as well as the risk which may impose on our next generation. A national wide
      survey is needed to investigate the intake of POPs, including POP pesticides, due
      to dietary differences, with a strong focus on the more sensitive populations,
      e.g., coastal residents who consume a large amount of fish.

PMID- 15949841
TI  - Effects of resin hydrophilicity on water sorption and changes in modulus of
      elasticity.
AB  - As acidic monomers of self-etching adhesives are incorporated into dental
      adhesives at high concentrations, the adhesive becomes more hydrophilic. Water
      sorption by polymers causes plasticization and lowers mechanical properties. The
      purpose of this study was to compare the water sorption and modulus of elasticity
      (E) of five experimental neat resins (EX) of increasing hydrophilicity, as ranked
      by their Hoy's solubility parameters and five commercial resins. METHODS: After
      measuring the initial modulus of all resin disks by biaxial flexure, half the
      specimens were stored in hexadecane and the rest were stored in water. Repeated
      measurements of stiffness were made for 3 days. Water sorption and solubility
      measurements were made in a parallel experiment. RESULTS: None of the specimens
      stored in oil showed any significant decrease in modulus. All resins stored in
      water exhibited a time-dependent decrease in modulus that was proportional to
      their degree of water sorption. Water sorption of EX was proportional to Hoy's
      solubility parameter for polar forces (delta(p)) with increasing polarity
      resulting in higher sorption. The least hydrophilic resin absorbed 0.55 wt% water
      and showed a 15% decrease in modulus after 3 days. The most hydrophilic
      experimental resin absorbed 12.8 wt% water and showed a 73% modulus decrease
      during the same period. The commercial resins absorbed between 5% and 12% water
      that was associated with a 19-42% reduction in modulus over 3 days.

PMID- 15949843
TI  - Characterisation of dentin surfaces processed with KrF excimer laser radiation.
AB  - In the present work, the surface microtexture and chemical changes induced in
      human dentin by laser processing with KrF excimer laser radiation using fluences
      ranging from 0.5 to 20 J/cm2 were studied by SEM, XPS and FTIR. Two distinct
      behaviours were observed in the evolution of surface topography. In some samples,
      the laser-treated surface remained flat, independently of the fluence used. It
      was covered by a layer formed of redeposited ablation particles, which occluded
      the dentinal apertures. In other samples the surface topography depended on
      radiation fluence. When the fluence was lower than 1 J/cm2, preferential removal
      of intertubular dentin occurs, producing a columnar structure in which the
      columns are essentially formed of peritubular material. If the fluence exceeded 1
      J/cm2 the processed surface was flat and covered with resolidified material.
      Despite these topographic changes, the dentin was not significantly affected by
      the laser treatment. The observed behaviour can be explained by differences in
      the constitution of dentin.

PMID- 15949842
TI  - Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis
      clinical isolates from orthopaedic implant infections.
AB  - The opportunistic pathogen Staphylococcus epidermidis is able to produce biofilm
      and to frequently cause implant infections. In recent years, it has also
      exhibited an increasing antimicrobial drug resistance. Here, the resistance to a
      panel of 16 different antibiotics in 342 clinical strains of S. epidermidis from
      orthopaedic implant infections has been investigated. The isolates were pheno-
      and genotyped for extracellular polysaccharide production, relevant to
      staphylococcal biofilm formation, in order to ascertain possible associations
      with antibiotic resistance. Approximately 10% of the isolates were found to be
      sensitive to all screened antibiotics. In all, 37-38% were resistant to beta
      lactams such as oxacillin and imipenem, while the resistance to penicillin,
      ampicillin, cefazolin, cefamandole, was consistently observed in over 80% of the
      strains. Erythromycin- and clindamycin- resistant strains were approximately 41%
      and 16%, respectively. Of the isolates, 10% was resistant to chloramphenicol, 23%
      to sulfamethoxazole and 26% to ciprofloxacin. Resistance to vancomycin was never
      observed. Interestingly, exopolysaccharide-producing strains exhibited a
      significantly higher prevalence in the resistance to the four aminoglycosides
      (gentamicin, amikacin, netilmicin, tobramycin), to sulfamethoxazole and to
      ciprofloxacin with respect to non-producing isolates. Moreover, multiple
      resistance to antibiotics was more frequent among exopolysaccharide-forming
      strains.

PMID- 15949844
TI  - Specific properties of heavy fraction of mitochondria from human-term placenta -
      glycerophosphate-dependent hydrogen peroxide production.
AB  - Mitochondrial respiratory chain enzyme Complexes are present in placenta at
      proportion similar to other tissues with exception of glycerophosphate
      dehydrogenase (mGPDH) which is expressed at a very high rate. As shown by Western
      blot quantification and respiratory chain enzyme activity measurements, the
      specific content of mGPDH is similar to that of succinate dehydrogenase or NADH
      dehydrogenase. Using fluorometric probe dichlorodihydrofluorescein diacetate we
      found that placental mitochondria display high rate of glycerophosphate-dependent
      hydrogen peroxide production. This was confirmed by oxygraphic detection of
      glycerophosphate-induced, KCN- or antimycin A-insensitive oxygen uptake. Hydrogen
      peroxide production by mGPDH was highly activated by one-electron acceptor,
      potassium ferricyanide and it was depressed by inhibitors of mGPDH and by
      cytochrome c. Our results indicate that mGPDH should be considered as an
      additional source of reactive oxygen species participating in induction of
      oxidative stress in placenta.

PMID- 15949845
TI  - Toxicokinetics and biotransformation of p-nitrophenol in white sturgeon
      (Acipenser transmontanus).
AB  - White sturgeon (Acipencer transmontanus) were exposed to 7.2 microM (1.0 ppm) 14C
      labeled p-nitrophenol (PNP) in brackish water for 24 h and then allowed to
      depurate in clean brackish water for another 24h. Absorption, conditional uptake
      clearance, and conditional elimination rate constants were 0.08+/-0.04 h(-1),
      8.1+/-3.6 mL g(-1) h(-1), and 0.46+/-0.21 h(-1), respectively. A whole-organism
      total concentration factor of 18.7+/-2.6 was determined from equilibrium tissue
      and water concentrations. Sturgeon depurated 89.4% of absorbed PNP within 24h, of
      which 53.0+/-8.3% was unmetabolized parent compound, 9.6+/-3.6% was p-nitrophenyl
      beta-d-glucuronide, and 39.1+/-8.3% was p-nitrophenylsulfate.

PMID- 15949846
TI  - An evaluation of mixed species in-situ and ex-situ feeding assays: the altered
      response of Asellus aquaticus and Gammarus pulex.
AB  - Mixed species feeding assays were undertaken with pollution sensitive (Gammarus
      pulex) and tolerant (Asellus aquaticus) macro-invertebrates during August 2003
      and April 2004. The purpose of this study was to establish if a test animals'
      response is comparable during in-situ and ex-situ toxicity tests. Seven test
      sites were established along an undisclosed stream, which received leachate
      discharge from an unlined, disused UK landfill site. Sampling points A-B were
      upstream of the contamination, C was adjacent to the influx and D-G were
      downstream of the leachate discharge (at 100 m intervals). During the in-situ and
      ex-situ tests, 2-week-old male laboratory bred A. aquaticus and G. pulex were
      used as test animals. The animals were transplanted to the seven sampling points
      for the duration of the in-situ tests, whilst water samples from each site were
      returned to the laboratory for ex-situ testing. The results show that the
      animals' mortality and feeding rates followed similar trends during the in-situ
      and ex-situ tests, however, the animals' response was amplified during the in
      situ tests. It was also observed that the effects were greater in April, compared
      to August that may be attributed to a higher frequency of rainfall during spring,
      which could have flushed a greater proportion of the contaminant load from the
      waste mass and as a consequence, higher levels of pollution may have leached into
      the stream from the landfill site. The study, therefore, concludes that in-situ
      toxicity tests are a more precise monitoring technique, in comparison to ex-situ
      assays.

PMID- 15949847
TI  - Recent advances in the understanding of the role of nitric oxide in
      cardiovascular homeostasis.
AB  - Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO)
      generation. To date, 3 distinct NOS isoforms have been identified: neuronal NOS
      (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3). Biochemically, NOS
      consists of a flavin-containing reductase domain, a heme-containing oxygenase
      domain, and regulatory sites. NOS catalyse an overall 5-electron oxidation of one
      Nomega-atom of the guanidino group of L-arginine to form NO and L-citrulline. NO
      exerts a plethora of biological effects in the cardiovascular system. The basal
      formation of NO in mitochondria by a mitochondrial NOS seems to be one of the
      main regulators of cellular respiration, mitochondrial transmembrane potential,
      and transmembrane proton gradient. This review focuses on recent advances in the
      understanding of the role of enzyme and enzyme-independent NO formation,
      regulation of NO bioactivity, new aspects of NO on cardiac function and
      morphology, and the clinical impact and perspectives of these recent advances in
      our knowledge on NO-related pathways.

PMID- 15949848
TI  - Migration of dendritic cells into the brain in a mouse model of prion disease.
AB  - The immune system plays a key role in the dissemination of prion infections from
      the periphery to the central nervous system (CNS). While follicular dendritic
      cells are critical for prion replication in lymphoid tissue and subsequent
      neuroinvasion, myeloid dendritic cells (DCs) have been implicated in both the
      clearance and propagation of pathological prion protein. Since nothing is known
      on the ability of DCs to migrate to the CNS during prion diseases, we
      investigated the immunohistochemical localization of CD205(+) DCs in the brain of
      C57BL/6 mice intraperitoneally infected with the mouse-adapted KFu strain of
      Gerstmann-Straussler-Scheinker syndrome, a human genetic prion disorder. In
      normal brain, CD205(+) cells were present in the meninges and choroid plexus,
      whereas in the majority of mice sacrificed between 120 and 300 days post
      infection, CD205(+) DCs were also detected in the cerebral cortex, subcortical
      white matter, thalamus and medulla oblongata. These findings demonstrate that DCs
      can enter the CNS of prion-infected mice, suggesting a possible role for these
      cells in the pathogenesis of prion disorders.

PMID- 15949849
TI  - Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic
      neurological syndromes.
AB  - We describe a new antibody, called anti-glial nuclear antibody (AGNA), in
      patients with paraneoplastic neurological syndromes (PNS) and small-cell lung
      carcinoma (SCLC). AGNA was initially identified in 24 sera of our archives by
      immunohistochemistry on rat cerebellum. AGNA positive sera showed a
      characteristic nuclear staining of the Bergmann glia in the Purkinje cell layer.
      Immunoblots and probing a cerebellar expression library with AGNA sera did not
      identify the antigen. Twenty of the 24 patients with AGNA had PNS and all but two
      had lung cancer. AGNA was identified in 13/113 (11.5%) patients with SCLC
      compared with 0/122 with other types of cancer (p<0.0001). The frequency of AGNA
      was not higher than expected for the presence of SCLC in the different PNS
      subtypes except in LEMS (p=0.0002). AGNA was present in 13/30 (43%) of LEMS
      patients with SCLC, compared with 0/19 of LEMS patients without cancer
      (p=0.0006). We conclude that the recognition of AGNA is helpful since this
      antibody is found in PNS associated with SCLC, particularly LEMS, in which other
      onconeural antibodies are absent.

PMID- 15949850
TI  - Immunological patterns identifying disease course and evolution in multiple
      sclerosis patients.
AB  - Reliable, and easy to measure, immunological markers able to denote disease
      characteristics in multiple sclerosis (MS) patients are still lacking. We applied
      a multivariate statistical analysis on results obtained by measuring-by real-time
      RT-PCR-mRNA levels of 25 immunological relevant molecules in PBMCs from 198 MS
      patients. The combined measurement of mRNA levels of IL-1beta, TNF-alpha, TGF
      beta, CCL20 and CCR3 was able to distinguish MS patients from healthy
      individuals. CXCR5, CCL5, and CCR3 combined mRNA levels identify primary
      progressive MS patients while TNF-alpha, IL-10, CXCL10 and CCR3 differentiate
      relapsing MS patients. Our results indicate that multi-parametric analysis of
      mRNA levels of immunological relevant molecules in PBMCs may represent a
      successful strategy for the identification of putative peripheral markers of
      disease state and disease activity in MS patients.

PMID- 15949851
TI  - Middle ear total pressure measurement as a useful parameter for outcome
      prediction in pediatric otitis media with effusion.
AB  - OBJECTIVE: For the effective treatment of pediatric otitis media with effusion
      (OME) with a ventilation tube, routine evaluation of the condition of the middle
      ear mucosa after tube placement is critical. For this purpose, we monitored the
      changes in the middle ear total pressure (METP) associated with the transmucosal
      gas exchanges. We also evaluated the function of the eustachian tube by
      sonotubometry. The present study aimed to examine the temporal changes in the
      maximum METP after tube placement and to assess the association between the
      maximum METP and subsequent outcome. We also investigated the predictive value of
      METP measurement and sonotubometry on tube removal. METHODS: To study the
      temporal changes in the maximum METP after tube placement and the association
      between the maximum METP and outcome after tube removal, 78 patients were
      enrolled, who underwent ventilation tube placement between April 1991 and May
      2002 and were followed up for at least a year after tube removal. Of these 78
      patients, 54 patients who underwent the METP measurement on tube removal and 39
      patients who underwent sonotubometry on tube removal were included in a
      retrospective analysis of the predictive value of these tests. The patients were
      divided into 4 groups according to the outcome after tube removal, graded as
      "excellent", "good", "persistent perforation" and "recurrence". RESULTS: The
      maximum METP exhibited a tendency to increase after 18 months or longer of tube
      placement. The comparisons of the maximum METP across the patient groups revealed
      that the maximum METP in patients with "excellent" was significantly higher than
      that in patients with "recurrence" (Student's t-test, P<0.05). As for the
      prediction of outcomes on tube removal, 32.4 and 57.1% of patients were predicted
      to have a good outcome by sonotubometry and the METP measurement, respectively
      (chi2 test, P<0.05). Among patients with a maximum METP higher than 31 mm H2O,
      93.3% exhibited no recurrence after tube removal. CONCLUSIONS: Favorable outcome
      after tube removal was associated with more active transmucosal gas exchange. The
      maximum METP best reflected the outcome after tube removal, indicating a superior
      predictive value of the METP measurement over sonotubometry.

PMID- 15949853
TI  - Baroreflex sensitivity normalization after cardiac resynchronization therapy.

PMID- 15949852
TI  - Inhibition of NF-kappaB activation and expression of inflammatory mediators by
      polyacetylene spiroketals from Plagius flosculosus.
AB  - Transcription factor NF-kappaB plays a key role for the inducible expression of
      genes mediating proinflammatory effects and is thus an important target for the
      development of antiinflammatory drugs. Here, we show that extracts from the plant
      Plagius flosculosus (L.) Alavi and Heyw. can inhibit the induction of NF-kappaB
      activity, and we describe the identification of three spiroketal compounds. Of
      those, only compound 1 could inhibit the phosphorylation and proteasomal
      degradation of IkappaB, thus preventing the nuclear import and DNA binding of NF
      kappaB. Accordingly, compound 1, which is also found in the widely used medicinal
      herb chamomile, interfered with the LPS-induced production of IL-1, IL-6, TNF,
      and PGE2 in primary human monocytes.

PMID- 15949854
TI  - Post cardiac surgery diaphragmatic spasm successfully treated with gabapentin.
AB  - We describe the case of an 82 year old woman developing severe respiratory
      functional impairment after open heart surgery and subsequent surgical
      pericardial drainage inducing diaphragmatic spasm and successfully treated with
      gabapentin.

PMID- 15949856
TI  - PCR-based gene disruption and recombinatory marker excision to produce modified
      industrial Saccharomyces cerevisiae without added sequences.
AB  - The dominant selectable Kanr marker, which confers geneticin resistance in yeast,
      is extensively used for PCR based disruption of genes in functional analysis
      studies in laboratory strains of Saccharomyces cerevisiae. We have developed a
      gene disruption cassette, which incorporates the Kanr marker, and direct repeat
      sequences designed from the target gene to enable the deletion of the gene
      without the introduction of added DNA sequences. We report on the disruption of
      the HO gene as a test case, using the hodr-Kanr-hodr cassette. The cassette was
      shown to integrate at the HO locus and the Kanr marker excised by recombination
      between the two direct repeat sequences. The disruption/excision event resulted
      in the removal of one direct repeat and the coding sequence of the gene, and
      hence in this case loss of HO function, with the introduction of no foreign or
      additional sequences, including the Kanr marker. Having been derived from the
      target site, the remaining direct repeat sequence is native sequence in its
      native location. This design template has the potential to be adapted to other
      genes, and as such will be of advantage in instances such as the optimization of
      strains by recombinant DNA technology where the retention of minimal or no
      foreign sequences is desired.

PMID- 15949857
TI  - Development of solution phase hybridisation PCR-ELISA for the detection and
      quantification of Enterococcus faecalis and Pediococcus pentosaceus in Nurmi-type
      cultures.
AB  - Nurmi-type cultures (NTCs), derived from the fermentation of caecal contents of
      specifically pathogen-free (SPF) birds, have been used successfully to control
      salmonella colonisation in chicks. These cultures are undefined in nature and,
      consequently, it is difficult to obtain approval from regulatory agencies for
      their use as direct fed microbials (DFMs) for poultry. Progress towards the
      generation of effective defined probiotics requires further knowledge of the
      composition of these cultures. As such, species-specific, culture-independent
      quantification methodologies need to be developed to elucidate the concentration
      of specific bacterial constituents of NTCs. Quantification of specific bacterial
      species in such ill-defined complex cultures using conventional culturing methods
      is inaccurate due to low levels of sensitivity and reproducibility, in addition
      to slow turnaround times. Furthermore, these methods lack selectivity due to the
      nature of the accompanying microflora. This study describes the development of a
      rapid, sensitive, reliable, reproducible, and species-specific culture
      independent, solution phase hybridisation PCR-ELISA procedure for the detection
      and quantification of Enterococcus faecalis and Pediococcus pentosaceus in NTCs.
      In this technique, biotin-labelled primers were designed to amplify a species
      specific fragment of a marker gene of known copy number, in both species.
      Resulting amplicons were hybridised with a dinitrophenol (DNP)-labelled
      oligonucleotide probe in solution and were subsequently captured on a
      streptavidin-coated microtitre plate. The degree of binding was determined by the
      addition of IgG (anti-DNP)-horseradish peroxidase conjugate, which was
      subsequently visualised using a chromogenic substrate, tetramethylbenzidine. This
      novel quantitative method was capable of detecting E. faecalis and P. pentosaceus
      at levels as low as 5 CFU per PCR reaction.

PMID- 15949858
TI  - Alternative primer sets for PCR detection of genotypes involved in bacterial
      aerobic BTEX degradation: distribution of the genes in BTEX degrading isolates
      and in subsurface soils of a BTEX contaminated industrial site.
AB  - Eight new primer sets were designed for PCR detection of (i) mono-oxygenase and
      dioxygenase gene sequences involved in initial attack of bacterial aerobic BTEX
      degradation and of (ii) catechol 2,3-dioxygenase gene sequences responsible for
      meta-cleavage of the aromatic ring. The new primer sets allowed detection of the
      corresponding genotypes in soil with a detection limit of 10(3)-10(4) or 10(5)
      10(6) gene copies g(-1) soil, assuming one copy of the gene per cell. The primer
      sets were used in PCR to assess the distribution of the catabolic genes in BTEX
      degrading bacterial strains and DNA extracts isolated from soils sampled from
      different locations and depths (vadose, capillary fringe and saturated zone)
      within a BTEX contaminated site. In both soil DNA and the isolates, tmoA-, xylM-
      and xylE1-like genes were the most frequently recovered BTEX catabolic genes.
      xylM and xylE1 were only recovered from material from the contaminated samples
      while tmoA was detected in material from both the contaminated and non
      contaminated samples. The isolates, mainly obtained from the contaminated
      locations, belonged to the Actinobacteria or Proteobacteria (mainly Pseudomonas).
      The ability to degrade benzene was the most common BTEX degradation phenotype
      among them and its distribution was largely congruent with the distribution of
      the tmoA-like genotype. The presence of tmoA and xylM genes in phylogenetically
      distant strains indicated the occurrence of horizontal transfer of BTEX catabolic
      genes in the aquifer. Overall, these results show spatial variation in the
      composition of the BTEX degradation genes and hence in the type of BTEX
      degradation activity and pathway, at the examined site. They indicate that
      bacteria carrying specific pathways and primarily carrying tmoA/xylM/xylE1
      genotypes, are being selected upon BTEX contamination.

PMID- 15949859
TI  - Phase synchronization between theta and upper alpha oscillations in a working
      memory task.
AB  - Motivated by findings that theta and upper alpha oscillations respond selectively
      to different types of memory demands, we investigated the role of phase
      synchronization in a memory scanning task. During retention, we found a load
      dependent increase in upper alpha power at O2 and P4 and a significant upper
      alpha:theta phase synchronization between right posterior, central and left
      anterior sites. During retrieval, a load dependent increase in upper alpha phase
      locking was observed at O2 and an increase in upper alpha:theta phase
      synchronization between right posterior and left anterior sites. We suggest that
      theta reflects central executive functions whereas upper alpha may be important
      for the reactivation of long-term memory codes in short-term memory. The
      interplay between theta and upper alpha may be reflected by phase synchronization
      between these frequencies.

PMID- 15949860
TI  - The effect of eye closure on the flash visual evoked potentials in Alzheimer's
      disease.

PMID- 15949861
TI  - Synergistic effect of poly(ethylenimine) on the transfection efficiency of
      galactosylated chitosan/DNA complexes.
AB  - The use of chitosan for gene delivery is limited due to the low transfection
      efficiency and difficulty in transfecting into a variety of cell types,
      especially the hepatoma cells. In order to solve this problem, lactobionic acid
      (LA) bearing galactose group was coupled with water-soluble chitosan (WSC) for
      liver specificity and poly(ethylenimine) (PEI) was combined to galactosylated
      chitosan (GC)/DNA complexes to enhance the transfection efficiency. For initial
      study, the effect of PEI on the transfection efficiency of WSC/DNA complex was
      studied in HeLa, A549 and 293 T cells, and bafilomycin A1 was used to ascertain
      the mechanism of synergistic effect. Transfection efficiency, cytotoxicity, and
      physicochemical properties of GC/DNA complex combined with PEI were investigated
      to determine the potential for the hepatocyte-targeting. The combination of PEI
      with WSC/DNA and GC/DNA complex dramatically increased the luciferase expression
      10- to 1000-fold in various cell lines, and the synergistic effect was proved to
      be induced by proton sponge effect of PEI. The transfection of GC/DNA complex in
      HepG2 was much higher than that of WSC/DNA even after combination with PEI, and
      was highly inhibited in the presence of galactose. Cytotoxicity of PEI was much
      decreased by combination with GC/DNA complex. And PEI was proved to be coated on
      the surface of GC/DNA complex through the ionic interaction.

PMID- 15949862
TI  - Secondary sulfonylurea failure: comparison of period until insulin treatment
      between diabetic patients treated with gliclazide and glibenclamide.
AB  - We retrospectively evaluated a possible difference in periods until start of
      insulin treatment between type 2 diabetic patients treated with gliclazide (GCZ)
      and glibenclamide (GBC), because GCZ might be protective for beta cells than GBC.
      Subjects were Japanese patients. GCZ group consisted of patients treated with GCZ
      alone or with GCZ and GBC in the separate treatment periods in combination with
      or without other oral hypoglycemic agents (OHAs), while GBC group consisted of
      patients with GBC alone or in combination with other OHAs except GCZ. The periods
      until the treatment of insulin commenced were calculated using the Kaplan-Meier
      method. Proportional hazards models were used to adjust the differing variables
      between GCZ and GBC groups. The periods until the start of insulin treatment from
      diabetes onset, diabetes treatment, or GCZ or GBC treatment were significantly
      longer in the GCZ group than those in GBC group (P<0.001 in each group).
      Independent variables affecting the period were average HbA1c levels during GCZ
      or GBC treatment (hazard ratio=2.5 per %), other OHAs combined (hazard ratio=1.9
      on combination), and difference between GCZ and GBC groups (hazard ratio=0.5 on
      GCZ). These results imply that GCZ may be more protective against secondary beta
      cell failure than GBC.

PMID- 15949863
TI  - Diabetes induces Na/H exchange activity and hypertrophy of rat mesenteric but not
      basilar arteries.
AB  - Experimental hyperglycemia produces a marked hypertrophic response in rat
      mesenteric arteries, accompanied by activation of Na/H exchange (NHE) in medial
      smooth muscle. This study asked if other vascular beds are similarly affected by
      examining the hypertrophic and NHE response of the basilar artery. Sections of
      mesenteric and basilar arteries from adult rats were analysed by standard
      morphometric techniques at 1 and 3 weeks after streptozotocin injection. NHE
      activity was assessed as changes in intracellular pH in isolated intact vessels
      using concurrent myography and fluorescence spectroscopy. Mesenteric arteries
      showed a significant increase in lumenal (47%), medial (51%) and adventitial
      (17%) area. In contrast, these parameters were not increased in basilar arteries
      from the same set of animals. Maximal NHE activity was significantly increased at
      1 week (24%) and 3 weeks (20%) in mesenteric arteries, but in basilar arteries
      there was no change in basal intracellular pH, maximal NHE activity or kinetic
      properties of the transporter. NHE plays a central role in vascular changes in
      diabetes. As the mesenteric hypertrophy is amenable to therapeutic intervention
      these findings add further to the potential of NHE as a therapeutic target for
      ameliorating vascular disease in diabetes.

PMID- 15949864
TI  - Identification of a bacterial regulatory system for ribonucleotide reductases by
      phylogenetic profiling.
AB  - Using comparative genomics approaches, we analyzed the regulation of
      ribonucleotide reductase genes in bacterial genomes. A highly conserved
      palindromic signal with consensus acaCwAtATaTwGtg, named NrdR-box, was identified
      upstream of most operons encoding ribonuleotide reductases from three different
      classes. By correlating the occurrence of NrdR-boxes with phylogenetic
      distribution of ortholog families, we identified a transcriptional regulator
      containing Zn-ribbon and ATP-cone motifs (COG1327) for the predicted
      ribonucleotide reductase regulon. Further characterization of the regulon and
      metabolic reconstruction of the regulated pathways demonstrated its functional
      link to replication. The method of simultaneous phylogenetic profiling of genes
      and conserved regulatory signals introduced in this study could be used to
      identify transcriptional factors regulating orphan regulons.

PMID- 15949865
TI  - Sex determination: a tale of two Sox genes.
AB  - Vertebrates use many different strategies to determine sex, but the Sox9 gene is
      a common thread, probably acting as the pivotal gene that controls the male
      determining pathway. It now appears that Sox9 is not alone in this role, and that
      a closely related gene, Sox8, can partly substitute for Sox9. But is this a
      clever backup strategy to safeguard male development, or a relic of the past?

PMID- 15949866
TI  - Novel target sites in bacteria for overcoming antibiotic resistance.
AB  - Resistance to marketed antibiotics continues to increase. During the last 10
      years some 200 bacterial genome sequences have become available, giving rise to
      expectations that genomics would provide a plethora of novel targets and hence a
      flood of new therapeutic agents. Contrary to some predictions the genomic effort
      has yet to yield a substantial number of novel class agents in clinical
      development. What are the reasons for the differences between expectations and
      reality? This article reviews what has been achieved in the exploitation of
      bacterial genomes for the discovery of novel antibacterials.

PMID- 15949867
TI  - Antibiotic resistance-the problem intensifies.
AB  - While previously recognized antibiotic-resistant bacteria continue to increase in
      frequency and numbers globally, new resistance problems have recently emerged
      which further complicate and impede treatment of critical infectious diseases.
      Vancomycin resistance among Staphylococcus aureus, extended spectrum beta
      lactamases among gram-negative pathogens, and fluoroquinolone resistance among
      already multidrug-resistant Escherichia coli and Neisseria gonorrheae are adding
      to the toll of resistance on patients suffering with infectious diseases.

PMID- 15949868
TI  - No association between the C-1562T polymorphism in the promoter of matrix
      metalloproteinase-9 gene and non-small cell lung carcinoma.
AB  - The matrix metalloproteinases (MMPs) are a family of highly conserved metal
      dependent proteolytic enzymes, their main function is to degrade different
      components of extracellular matrix (ECM). Moreover, they play roles in regulation
      of cell growth, apoptosis, angiogenesis and immune surveillance. Natural sequence
      variations in the MMP genes may result in differential expression of MMPs in
      different individuals and therefore may be associated with the development and
      progression of diseases. The aim of this study is to assess the effects of the C
      1562T polymorphism in the MMP-9 promoter on the risk of occurrence and lymphatic
      metastasis of non-small cell lung carcinoma (NSCLC). The MMP-9 genotyping was
      performed in 243 pathologically diagnosed NSCLC patients and 350 healthy controls
      without overt cancer by using polymerase chain reaction-restriction fragment
      length polymorphism analysis. The distribution of the MMP-9 genotypes in NSCLC
      patients and healthy controls was in consistent with Hardy-Weinberg equilibrium.
      The frequency of the C/C, C/T and T/T genotypes in healthy controls was 79.4,
      20.6 and 0%, respectively. Neither the overall genotype nor allelotype
      distribution in NSCLC patients showed significant difference from that in healthy
      controls (P=0.21 and 0.43, respectively). Compared with the C/C genotype,
      genotypes with the T allele did not show significant influence on the risk of
      NSCLC development (age and gender adjusted OR=1.13, 95% CI=0.76-1.68).
      Stratification by onset age, smoking status and tumor histological type also
      showed no association between the MMP-9 polymorphism and the risk of NSCLC.
      Furthermore, the genotype distribution between NSCLC patients with and without
      lymphatic metastasis was not significantly different. Therefore, the present
      study suggests that the MMP-9 C-1562T polymorphism may not be used as a useful
      marker to predicate susceptibility and lymphatic metastasis in NSCLC.

PMID- 15949869
TI  - Individual differences in reward sensitivity are related to food craving and
      relative body weight in healthy women.
AB  - According to the theory of J.A. Gray, a strongly reactive approach system is
      highly sensitive to reward or to cues that signal reward. This implies that
      intake driven by the rewarding properties of food should be affected by
      individual differences in reactivity of the approach system. The present study
      examined whether reward sensitivity is associated with food craving and relative
      body weight in a sample of female college students. Participants completed the
      Sensitivity to Punishment and Sensitivity to Reward Questionnaire and the trait
      version of the Food Craving Questionnaire and also reported their weight and
      height in order to compute Body Mass Index (BMI). Sensitivity to reward was
      significantly related to food craving and BMI. Furthermore, the correlation
      between reward sensitivity and BMI was not attenuated when the influence of food
      craving was partialled out, indicating that the relation between sensitivity to
      reward and BMI was not mediated by food craving. This is the first study
      demonstrating a relation between the personality trait of sensitivity to reward
      and BMI. These findings are discussed in the context of the involvement of
      dopaminergic reward circuitry in overeating.

PMID- 15949870
TI  - Transparency of the meat chain in the light of food culture and history.
AB  - Current patterns of meat consumption are considered to be unsustainable.
      Sustainable development may require that consumers choose to eat smaller
      quantities of meat as well as meat that is produced in a more sensible way. A
      policy tool directed at consumer behaviour is that of enhancing consumer-oriented
      transparency of the production chain. Transparency is expected to allow people to
      make more mindful consumption choices, in line with their personal values. As
      most dietary habits are deeply rooted in the past, an assessment of the effect of
      transparency on food choices requires a historical perspective to food culture.
      Such a perspective provides us with at least two trends of relevance to meat
      consumption: increased concern for animal welfare and an ongoing dissociation of
      meat from its animal origin. Combined, these two trends may interact to allow
      people to consume in ways that actually conflict with their personal values:
      their concern for animal welfare does not translate into corresponding food
      choices, as the product meat does not remind them of its animal origin. An
      experiment was designed to test the hypothesis that people sensitive to animal
      welfare will respond to increased salience of animal origin and of animal
      welfare, and that they will show this by either avoiding to buy meat or by
      favouring free range and organic meat. Results confirmed the expected effect. The
      effect was observed mainly among those with Universalistic values, which limits
      the ultimate prospects of transparency as a policy tool.

PMID- 15949872
TI  - Relationships between the Food Expectancy Questionnaire (FEQ) and the Food
      Frequency Questionnaire (FFQ).
AB  - The outcome expectancies of 250 respondents were examined using the Food
      Expectancy Questionnaire (FEQ), comparing expectancies about four different
      foods: fruit, vegetables, chocolate and sweets and plain biscuits. These
      expectancies were related to diet as assessed by a Food Frequency Questionnaire.
      As with alcohol expectancies [Jones, B. T., Corbin, W. & Fromme, K. (2001). A
      review of expectancy theory and alcohol consumption. Addiction, 96, 57-72], on
      which this research was modelled, positive and negative outcomes were the main
      factors for all foods, accounting jointly for between 33 and 40% of expectancy
      variance in factor analysis and predicting as much as 16% of the variance in
      relevant food intake measures by linear regression. Expected positive and
      negative outcomes of eating were predominantly immediate psychological after
      effects, rather than including orosensory experiences, or longer-term effects on
      health or well-being. Other expectancies varied from food to food. FEQ
      expectancies for different foods have similar factor structure and were related
      to self-reported diet, the FEQ therefore shows promise as a means of modelling
      cognitions about eating.

PMID- 15949871
TI  - Microanalysis of eating behavior of three leptin deficient adults treated with
      leptin therapy.
AB  - Leptin deficiency has been associated with extreme obesity and hyperphagia in
      rodents and humans. A rare genetic disorder in humans yields the absence of the
      hormone leptin, extreme obesity, and a ravenous appetite. Reports on these rare
      cases have indicated that therapy using leptin injections can yield significant
      weight loss and changes in appetite. The aim of this report on acute leptin
      therapy in three leptin deficient adults was to provide a microanalysis of
      changes in eating behavior and ratings of hunger and satiety. In addition to
      substantial weight loss, 15 weeks of leptin therapy was associated with
      approximately 50% reduction in food intake and substantial changes in ratings of
      hunger and satiety before most meals. After short-term leptin therapy, the three
      participants ate until ratings indicated they were satiated, which was comparable
      to the ratings before leptin therapy. These findings suggest that one of the
      primary effects of acute leptin therapy may be to reduce the ravenous hunger
      associated with leptin deficiency, resulting in reduced food intake and
      significant weight loss. These results are discussed in the context of the
      scientific literature pertaining to leptin and its effects on appetite and
      obesity.

PMID- 15949873
TI  - [Strongyloides stercoralis infection simulating polyarteritis nodosa].
AB  - INTRODUCTION: Parasitic infection can present with many different clinical
      manifestations. EXEGESIS: A 77 year-old Russian woman, who's been living in
      France since 50 years was admitted for polyarthritis, myalgia, fever, abdominal
      pain, and eosinophilia simulating polyarterisis nodosa. Before admission, she was
      treated by steroids for polymyalgia rheumatica. The diagnosis of Strongyloides
      stercoralis was performed by parasitologic analysis of feces and colic biopsies.
      The outcome was favourable under treatment by ivermectine and steroid withdrawal.
      CONCLUSION: S. stercoralis can be associated with reactive arthritis. Case
      reports of S. stercoralis infection mimicking systemic vasculitis are
      exceptionnal.

PMID- 15949874
TI  - [Scurvy, a re-emerging disease].
AB  - BACKGROUND: Scurvy is the clinical manifestation of vitamin C deficiency. It is
      historically linked to the era of great maritime expeditions. But it is remerging
      in Western countries as in France. SITUATION: Nowadays, scurvy mainly affects
      homeless populations of large occidental cities and the isolated and malnourished
      inhabitants of developing countries. The clinical presentations of scurvy are
      numerous and often misleading and its evolution without treatment is always
      lethal. After years of wanderings and research, the physiopathological mechanisms
      of scurvy were finally understood, due to the will of outstanding personalities
      who took the risk to brave the established superstitions in order to apply a
      strict medical approach. PERSPECTIVES: Scurvy must still be prevented in at risk
      populations. Indeed a pocket meal enriched with vitamin C is distributed to
      homeless people in Paris.

PMID- 15949876
TI  - Effects of repeated drill use on temperature of bone during preparation for
      osteosynthesis self-tapping screws.
AB  - Drills used during preparation for osteosynthesis with self-tapping screws are
      often used repeatedly until they become blunt and ineffective. Because the
      sharpness of the drill is one of the most important factors in its cutting
      efficiency, blunt drills may require the application of extra force, which in
      turn may contribute to excessive frictional heat produced during preparation of
      screw holes. Large rises in temperature can impair bony regeneration around
      screws and contribute to failure of internal fixation. In an attempt to quantify
      the potential increase in temperature produced by blunt drills, we devised an in
      vitro experiment to simulate preparation for osteosynthesis by using drills with
      different degrees of wear. Three drills were used: one was new, one had drilled
      600 holes, and the third drill had been in use in theatre for several months. The
      mean (range) rise in temperature for the three drills were: new drill 7.5 degrees
      C (0.6-20.5 degrees C); drill after 600 holes 13.4 degrees C (5.7-28.3 degrees
      C); and drill from theatre 25.4 degrees C (12.4-41.3 degrees C). There was a
      highly significant difference in the temperatures generated by the three drills,
      and the changes in temperature were related to the amount of wear. The cost of
      drills is low, and as their repeated use can compromise the results of the
      operation they must be discarded after single use.

PMID- 15949877
TI  - Recurrent nodal metastases in the posterior triangle: implications for treatment
      of the atypical tumour.
AB  - We studied the incidence of recurrent nodal metastases in level V (posterior
      triangle) in patients who had previously had a staging or therapeutic dissection
      of the neck, with or without postoperative radiotherapy. Of 160 patients studied
      (177 neck dissections), 41 (26%) developed recurrent metastases in the neck. Four
      patients (3%) developed ipsilateral recurrent disease in level V. In these four
      patients, level III or IV lymph nodes were shown histologically to have
      extracapsular spread at the time of the original dissection. All four metastases
      were located at or just beyond the anatomical boundaries of the posterior
      triangle. None of the metastases at level V were from oral or oropharyngeal
      primary tumours.

PMID- 15949878
TI  - Prediction of [3-(14)C]phenyldodecane biodegradation in cable insulating oil
      spiked soil using selected extraction techniques.
AB  - This study investigated the use of an aqueous hydroxypropyl-beta-cyclodextrin
      (HPCD) shake extraction in predicting microbial mineralisation and total loss of
      [3-(14)C]phenyldodecane associated activity in soils spiked with cable insulating
      oil; phenyldodecane represents a major constituent of cable insulating oil.
      Direct comparisons were made between freshly spiked and aged soils, and following
      composting. Soil was spiked with [3-(14)C]phenyldodecane (10mg kg(-1)) and stored
      in microcosms and aged for 1, 23, 44, 65, 90 and 153 d. At each sample time
      point, a variety of analyses were performed to assess the relationship between
      chemical and biological techniques in determining mineralisation and loss of
      (14)C-activity in soils under composting and non-composting conditions. Methods
      included determination of total (14)C-activity remaining, dichloromethane (DCM)
      and HPCD extractions. Mineralisation assays were also carried out to quantify the
      fraction of (14)C-phenyldodecane associated activity available for degradation in
      the soil at each time point. DCM and HPCD extractability were compared to
      contaminant mineralisation and to total loss of (14)C-phenyldodecane associated
      activity from the microcosms, after 153 d incubation. Poor relationships were
      found between (i) the amount of (14)C-activity mineralised and the fraction
      removed from the soils using DCM extraction and (ii) DCM extraction and total
      loss of [(14)C]phenyldodecane associated activity from the soil systems. Good
      relationships were observed between (i) the amount of (14)C-activity mineralised
      and the fraction removed from the soils using the HPCD extraction and (ii) HPCD
      extraction and total loss of [(14)C]phenyldodecane associated activity from the
      soil systems. The results of this study indicate that an aqueous HPCD extraction
      may be a useful tool in assessing the microbial availability of phenyldodecane in
      freshly and aged spiked soils.

PMID- 15949879
TI  - Adsorption of arsenate on soils. Part 2: modeling the relationship between
      adsorption capacity and soil physiochemical properties using 16 Chinese soils.
AB  - An attempt has been made to elucidate the effects of soil properties on arsenate
      adsorption by modeling the relationships between adsorption capacity and the
      properties of 16 Chinese soils. The model produced was validated against three
      Australian and three American soils. The results showed that nearly 93.8% of the
      variability in arsenate adsorption on the low-energy surface could be described
      by citrate-dithionite extractable Fe (Fe(CD)), clay content, organic matter
      content (OM) and dissolved organic carbon (DOC); nearly 87.6% of the variability
      in arsenate adsorption on the high-energy surface could be described by Fe(CD),
      DOC and total arsenic in soils. Fe(CD) exhibited the most important positive
      influence on arsenate adsorption. Oxalate extractable Al (Al(OX)), citrate
      dithionite extractable Al (Al(CD)), extractable P and soil pH appeared relatively
      unimportant for adsorption of arsenate by soils.

PMID- 15949880
TI  - Investigation of the efficiency of existing air pollution monitoring sites in the
      state of Kuwait.
AB  - The use of mathematical modelling for investigation of the efficiency of existing
      monitoring sites for the impact of SO(2) emissions from power stations in the
      state of Kuwait is described. The Industrial Source Complex Short Term (ISCST3)
      model is utilised to obtain the spatial and temporal variations of SO(2) over
      residential areas. Statistical comparison between the 50 highest daily measured
      and predicted SO(2) concentrations at six monitoring sites shows that the model
      is capable of generating results with accuracy of 60--94%. An important
      conclusion of this work is that the existing locations of the Kuwait-EPA
      monitoring stations are not suitable for measuring the actual impact of SO(2).
      Therefore, there is a need for relocation of these sites to register the highest
      levels of SO(2) emitted from the current power stations in the state of Kuwait.

PMID- 15949881
TI  - Estimation of element deposition derived from road traffic sources by using
      mosses.
AB  - Sixty moss samples were taken along transects of nine roads in Austria. The
      concentrations of 17 elements in four moss species were determined. There was a
      high correlation between several elements like Cu/Sb (0.906), Ni/Co (0.897) or
      Cr/V (0.898), indicating a common traffic-related source. Enrichment factors were
      calculated, showing highest enrichment levels for: Cr, Mo, Sb, Zn, As, Fe, V, Cu,
      Ni, and Co. For these elements, road traffic has to be assumed as a source, which
      is confirmed by a significant negative correlation of the concentrations in
      mosses to the distance from the road for most of these metals. The rate of
      decrease followed a log-shaped curve at most of the investigated transects,
      although the decline cannot be explained by a single model. Multiple regression
      analysis highlighted traffic density, distance from and elevation of the road as
      the most influencing factors for the deposition of the investigated elements.
      Heavy duty vehicles (HDVs) and light duty vehicles (LDVs) showed different
      patterns. A comparison of sites likely to be influenced by traffic emissions with
      average values for the respective regions showed no significant differences for
      road distances of more than 250 m. Nevertheless, at heavily frequented roads,
      raised deposition of some elements was found even at a distance of 1,000 m.

PMID- 15949882
TI  - A strategy to reduce the use of fish in acute ecotoxicity testing of new chemical
      substances notified in the European Union.
AB  - This study explores the applicability of a fish acute threshold (step-down) test
      approach for the assessment of new chemical substances notified in the EU. The
      proposed approach basically implies replacing the fish LC50 toxicity test with a
      simple acute threshold test and thus reducing the number of fish used and also
      costs. The fish test would be performed only at one concentration, the lowest
      between the EC50 concentrations obtained with previous testing with algae and
      daphnia. When fish would be more sensitive than algae and daphnia, testing with
      fish would be continued at lower concentrations (step-down). From step-down test
      results the LC50 value can be obtained by applying the binominal method of
      interpolation. These data can be used together with algal and daphnid data to
      provide the same Predicted No Effect Concentration values. The acute aquatic
      toxicity data used in this evaluation were extracted from the New Chemicals
      Database of the European Chemicals Bureau. The results show that 53.6-71.2%
      reduction of the number of fish used would be possible when applying this new
      testing strategy and suggest its use for regulatory purposes.

PMID- 15949883
TI  - Achieving the 'good life': why some people want latrines in rural Benin.
AB  - Nearly half the world's population lacks basic sanitation to protect their
      environment from human fecal contamination. Building a latrine is the first step
      on the sanitation ladder in developing countries where a majority of the
      population defecates in open or public areas. Public health programs to improve
      sanitation have consistently framed promotional messages in terms of fecal-oral
      disease prevention and largely fail to motivate changes in sanitation behavior. A
      qualitative consumer study using in-depth interviews with 40 household heads was
      carried out to explore the decision to install a pit latrine in rural Benin. The
      motives for installing a latrine are reported and variations across the
      interviews are examined. The paper asserts that at least one active drive (desire
      for change or dissatisfaction) from among 11 found is needed to motivate latrine
      adoption. Drives involved prestige, well-being, and situational goals. Health
      considerations played only a minor role, and had little if anything to do with
      preventing fecal-oral disease transmission. Drives varied with gender,
      occupation, life stage, travel experience, education, and wealth, and reflected
      perceptions of the physical and social geography of the village, linked to
      availability of open defecation sites, social structure, road access, and urban
      proximity. The results have broad implications for new messages and strategies to
      promote sanitation in developing countries.

PMID- 15949884
TI  - Hypothesis: minimal changes in neural transmission in schizophrenia: decreased
      glutamatergic and GABAergic functions in the prefrontal cortex.
AB  - As the pathophysiology, decreased glutamatergic neurotransmission in the
      postmortem prefrontal cortex of schizophrenics has been suggested to underlie the
      condition. But consistent reproducible results have not been seen with the
      molecular biological studies focused on examining glutamatergic parameters in
      schizophrenic brains. We noticed the lack of reproducibility of these studies and
      hypothesized that this was caused by "minimal (functional) changes" of
      schizophrenic pathophysiology that cannot be detected as a robust result by
      investigating only one marker (i.e., receptor). The authors then investigated
      glutamate levels, as well as mRNA expression of glutamate receptors and
      transporters simultaneously for the same schizophrenic and control brain samples,
      in order to detect the "minimal changes" of glutamatergic neurotransmission in
      schizophrenic synaptic clefts. The results showed a tendency of increased mGluRs
      and decreased EAAT2 mRNA in all Brodmann areas examined, but no significant
      difference was observed between schizophrenics and controls. To make these small
      changes of glutamatergic neurotransmission on the synaptic clefts more apparent,
      the "receptors/transporters ratio" (mGluRs/EAAT2 ratio) was calculated for each
      case and the results showed that the mGluRs/EAAT2 ratio was significantly
      increased in schizophrenics compared to controls. Glutamate levels, measured by
      HPLC, showed a decrease in the schizophrenics, but failed to reach statistical
      significance. The same phenomenon was recognized in our GABAergic study of
      schizophrenic brain. To interpret these results as a monism, the increase in
      mGluRs and the decrease of EAAT2 mRNA compensate for the decrease in glutamate
      transmission in the schizophrenic synaptic clefts. But these changes are small
      and failed to be statistically significant. The "receptors/transporters ratio"
      for each case magnified these changes, such that they became statistically
      significant.

PMID- 15949885
TI  - Genetic variants in the angiotensin I-converting-enzyme (ACE) and angiotensin II
      receptor (AT1) gene and clinical outcome in depression.
AB  - The insertion/(I)/deletion (D) polymorphism of the angiotensin-converting enzyme
      gene (ACE) is of increasing interest in etiology and treatment of various
      neuropsychiatric disorders. The present study aimed to replicate own earlier
      findings that depressive patients with the ACE D-allele are responding better to
      treatment with antidepressants than those with the II genotype. We further
      investigated a common polymorphism (A1166C) in the angiotensin II receptor gene
      (AT1) to examine a possibly combined influence. A sample of 273 patients with
      major depression, being treated with different classes of antidepressants, was
      enrolled in the study. Genotyping was carried out using a polymerase chain
      reaction and snapshot method, respectively, and the severity of depression was
      monitored using the HAMD-17 scale before and after 4 weeks of treatment. The ACE
      II genotypes showed poorer improvement in HAMD-17 scale after 4 weeks of
      treatment (ANOVA: F=4.49, p=0.01) than carriers with one or two D-alleles.
      Similarly, more than 70% of the AT1 CC homozygotes had a 50% reduction in the
      HAMD-17 scale within 4 weeks of treatment. Our data might further suggest that
      patients with a haplotype combining the CC and DD/ID genotypes respond better to
      treatment than those with either single allele. These results should however be
      replicated in future research.

PMID- 15949886
TI  - [The lateral brachial flap: retrospective study of its face's utilisation between
      1995 and 2002].
AB  - The lateral brachial flap is a fascio-cutaneus flap. This flap is secured. The
      functional and cosmetic sequelae are limited. The authors propose in this paper
      its utilisation as free flap in the reconstruction of facial defects. Thanks to
      its low morbidity, this free flap may be used in old patients.

PMID- 15949887
TI  - Trichloroethylene and cancer in humans: recognizing the need for an evidence
      based analysis.

PMID- 15949889
TI  - Comparing statistical and semantic approaches for identifying change from land
      cover datasets.
AB  - In this paper, we examine methods for integrating spatial data which apparently
      should be comparable because they are of the same data type or theme, but which
      are incompatible or discordant because the classes of that theme are different.
      For a variety of reasons including changes in methods, in understanding of the
      resource, and in policy initiatives in the commissioning of the survey, this
      problem is widespread in the results of natural resources surveys. We present two
      generic methods: one method is grounded in a statistical approach using
      discriminant analysis, and the other exploits the knowledge of experts. We use
      the context of land cover mapping of Great Britain to explore these approaches
      for integrating discordant data. We demonstrate that the expert-based approach
      gives very good levels of identification of locations with incompatible
      classifications at different times, and gives a much better rate of recognition
      of change. Some conclusions are made about the need to expand current metadata
      and data quality reporting to include descriptions of:- data conceptualisations,
      semantics and ontologies;- who decided and defined what the features of interest
      in a dataset are, and why. If the benefits of spatial data initiatives such as
      GRID, E-science and INSPIRE are to be fully realised then some method needs to be
      found to communicate that information most effectively to the potential user of
      the data.

PMID- 15949888
TI  - Detection and typing of human papillomavirus DNA in uterine cervices with
      coexistent grade I and grade III intraepithelial neoplasia: biologic progression
      or independent lesions?
AB  - OBJECTIVE: To examine the HPV type infection of cervical cone specimens with
      coexistent CIN1 and CIN3 lesions, in order to define if coexistence of low- and
      high-grade lesions in the same cervix represent different stages of evolution in
      a continuing process that is caused by a single viral type or independent lesions
      induced by different HPV types. STUDY DESIGN: The examined material included 43
      cases with coexistent CIN1 and CIN3 in the cone biopsy specimen. Detection and
      typing of HPV was made by RFLP-PCR. RESULTS: All CIN1 lesions were HPV positive,
      while three CIN3 lesions were HPV-negative. The proportion of agreement of the
      HPV type in the two lesions, excluding negative cases (n = 40), was 60% (95%
      confidence interval: 43.3-75.1). HPV 16 was the most common type in both CIN3
      (56.8%) and CIN1 (46.5%). CONCLUSIONS: The so-called morphologic progression of
      CIN is not always synonymous with biologic progression, since many coexistent CIN
      lesions are caused by different HPV types, and so represent different cell
      clones. Clonality of coexistent CIN lesions may be implicated in the evolution of
      CIN as other recent studies have shown.

PMID- 15949890
TI  - Impacts of ozone on the activities of asthmatics: revisiting the data.
AB  - This manuscript develops a conditional demand system for three activities (indoor
      chores and leisure, outdoor chores and active leisure, and outdoor inactive
      leisure), and considers how individuals' activity schedules respond to ozone
      pollution and asthma symptom severity. The data are for a sample of individuals
      living near Los Angeles. Our approach differs from earlier ones in that we use a
      system of equations that allows for correlations across activity types. The
      empirical results suggest that increased ozone levels have a statistically
      significant influence on the amount of time that asthmatics spend in one of the
      activities, even though the examined time period exhibited relatively low ozone
      levels. Elasticities are estimated to better indicate the sensitivity of humans'
      activity schedules to pollution levels, and the one ozone effect is shown to be
      fairly weak. This study adds to the existing literature on the influence of ozone
      on asthma and asthma sufferers, some of which finds a causal link while other
      studies do not. The study results are also of interest because the asthmatics in
      the sample are all adults, whereas some recent research showing a link between
      ozone and asthma has focused on children.

PMID- 15949891
TI  - Policy planning under uncertainty: efficient starting populations for simulation
      optimization methods applied to municipal solid waste management.
AB  - Evolutionary simulation-optimization (ESO) techniques can be adapted to model a
      wide variety of problem types in which system components are stochastic. Grey
      programming (GP) methods have been previously applied to numerous environmental
      planning problems containing uncertain information. In this paper, ESO is
      combined with GP for policy planning to create a hybrid solution approach named
      GESO. It can be shown that multiple policy alternatives meeting required system
      criteria, or modelling-to-generate-alternatives (MGA), can be quickly and
      efficiently created by applying GESO to this case data. The efficacy of GESO is
      illustrated using a municipal solid waste management case taken from the regional
      municipality of Hamilton-Wentworth in the Province of Ontario, Canada. The MGA
      capability of GESO is especially meaningful for large-scale real-world planning
      problems and the practicality of this procedure can easily be extended from MSW
      systems to many other planning applications containing significant sources of
      uncertainty.

PMID- 15949892
TI  - No evidence for epigenetic inactivation of fumarate hydratase in leiomyomas and
      leiomyosarcomas.
AB  - Germline mutations in Fumarate Hydratase (FH) cause the development of leiomyomas
      and leiomyosarcomas in the syndromes Multiple Cutaneous and Uterine Leiomyomata
      (MCUL1) and Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC). There is
      little evidence, however, that FH mutation plays a role in the development of
      sporadic leiomyomas or leiomyosarcomas. Such observations do not, however,
      exclude a role for FH in tumour development outside the context of MCUL1/HLRCC,
      as it is possible that FH expression could be silenced by epigenetic mechanisms.
      To explore this possibility we have developed a highly specific antibody to FH
      and analysed a series of forty-five fresh-frozen uterine leiomyomas and nine
      leiomyosarcomas for FH expression.

PMID- 15949893
TI  - Germline mutations of the paired-like homeobox 2B (PHOX2B) gene in neuroblastoma.
AB  - Hereditary predisposition to neuroblastoma accounts for less than 5% of
      neuroblastomas and is probably heterogeneous. Recently, a predisposition gene has
      been mapped to 16p12-p13, but has not yet been identified. Occurrence of
      neuroblastoma in association with congenital central hypoventilation and
      Hirschsprung's disease suggests that genes, involved in the development of neural
      crest-derived cells, may be altered in these conditions. The recent
      identification of PHOX2B as the major disease-causing gene in congenital central
      hypoventilation prompted us to test it as a candidate gene in familial
      neuroblastoma. We report a family with three first-degree relatives with
      neuroblastic tumours (namely two ganglioneuromas and one neuroblastoma) in one
      branch and two siblings with Hirschsprung's disease in another branch. A
      constitutional R100L PHOX2B mutation was identified in all three patients
      affected with tumours. We also report a germline PHOX2B mutation in one patient
      treated for Hirschsprung's disease who subsequently developed a multifocal
      neuroblastoma in infancy. Both mutations disrupt the homeodomain of the PHOX2B
      protein. No loss of heterozygosity at the PHOX2B locus was observed in the
      tumour, suggesting that haplo-insufficiency, gain of function or dominant
      negative effects may account for the oncogenic effects of these mutations. These
      observations identify PHOX2B as the first predisposing gene to hereditary
      neuroblastic tumours.

PMID- 15949894
TI  - Transcriptional deregulation of VEGF, FGF2, TGF-beta1, 2, 3 and cognate receptors
      in breast tumorigenesis.
AB  - Angiogenesis is an important event during the neoplastic process and is induced
      by the secretion of numerous growth factors from endothelial cells. Vascular
      endothelial growth factor (VEGF), basic fibroblastic growth factor (FGF2), and
      transforming growth factor-beta1, beta2, beta3 (TGF-beta1, 2, 3) and cognate
      receptors (TGF-betaRI, II, III) mRNA expression pattern was evaluated by RT-PCR
      in 25 breast cancer tissue samples and adjacent normal tissues, and correlated to
      clinicopathological features. Western blot analysis was performed to evaluate
      VEGF and TGF-beta1 protein levels. TGF-beta1 and TGF-beta3 mRNA levels were
      significantly different in breast cancer specimens of differing histology
      (ductal, lobular, other) (P=0.020 and P=0.043). No statistically significant
      difference was observed at the mRNA level of VEGF between normal and tumor
      tissues while elevated VEGF protein levels in tumors were associated with
      patients' menopausal status. A strong hormonal influence of ER and PR on TGF-beta
      mRNA expression was established. FGF2 transcript levels were substantially
      decreased in cancer compared to adjacent normal specimens (P=0.031). A disruption
      of mRNA co-expression patterns was observed in malignant breast tissues compared
      to controls. Western blot analysis revealed differences between VEGF and TGFbeta1
      mRNA and their corresponding protein levels. A substantial negative correlation
      of TGF-beta1 protein and TGF-beta1 mRNA levels (P=0.016) was demonstrated by
      breast tissue-pair analysis. Summarizing, our findings suggest that transcript
      levels of the examined markers in breast cancer are associated with menopausal
      and hormonal status, while their co-expression pattern is altered in malignant
      tissues compared to controls. In addition the difference between VEGF and TGF
      beta1 mRNA and protein levels observed, indicates that post-transcriptional
      mechanisms may regulate expression of these molecules in breast cancer.

PMID- 15949895
TI  - Relationship between slow-wave EEG bursts and heart rate changes in preterm
      infants.
AB  - The objective of the study is to explore interactions between cortical and
      autonomic functions in the first weeks of postnatal life. We investigated the
      behaviour of one-channel electroencephalogram (EEG) patterns and heart rate (HR)
      dynamics in preterm infants. In a group of 15 healthy preterm infants with a mean
      conceptional age (CA) of 36 weeks and a mean postnatal age of 17.5 days
      simultaneous registration of amplitude integrated EEG (aEEG) and HR pattern was
      performed during interfeeding intervals. Periods with a discontinuous EEG
      activity and a low heart-rate variability (HRV) were selected for further
      processing and averaging. It was found that spontaneous activity transients
      (SATs) or slow wave EEG bursts during "Trace alternant" (TA) can be accompanied
      by an HR acceleration of 1-2% (mean: 1.9, range: 0.6-3.5 beats/min) lasting
      approximately 5s (mean, range: 3.6-7.1s). The aim of the study is to give
      evidence of a coherent behaviour of EEG bursts and HR in the developing nervous
      system of preterm infants.

PMID- 15949896
TI  - Familial influences on basal salivary cortisol in an adult population.
AB  - To understand the underlying genetic and environmental sources of individual
      variation in basal cortisol levels, we collected salivary cortisol at awakening
      and at six fixed time points during the day in adult twins and their singleton
      siblings. Reported time of awakening was verified with heart rate and body
      movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins
      and 229 singleton siblings from 309 twin families. No differences in cortisol
      means and variances were found between twins and singleton siblings.
      Additionally, the correlations for DZ twins and siblings were not significantly
      different, indicating generalizability of twin study results to the general
      population. Genetic model fitting showed heritability for cortisol levels during
      the awakening period (34% for cortisol level at awakening and 32% for cortisol
      level at 30 min after awakening) but not for cortisol levels later during the
      day. The current study shows that, while cortisol levels in the awakening period
      are influenced by genetic factors, cortisol levels throughout most of the day are
      not heritable, indicating that future gene finding studies for basal cortisol
      should focus on the first hour post-awakening.

PMID- 15949898
TI  - Differences in impulsivity and sensation seeking between early- and late-onset
      alcoholics.
AB  - The personality traits of impulsivity and sensation seeking have been proposed as
      important features of early-onset alcoholism. Early-onset (EOA, n=62) and late
      onset (LOA, n=68 ) alcoholic inpatients were compared as to the severity of their
      substance use and related problems, and self-report scales measuring impulsivity
      (Barratt Impulsiveness Scale, version 11), sensation seeking (Sensation Seeking
      Scale), and aggressiveness (Buss Durkee Hostility Inventory). The symptom
      severity of the EOAs' alcohol-use disorder and related problems was higher than
      that of the LOAs. Furthermore, the EOAs had higher levels of impulsivity,
      sensation seeking, and aggression relative to the LOAs. The differences in
      impulsivity remained after an analysis controlling for the effect of
      aggressiveness. Finally, cigarette smoking was positively correlated with
      impulsiveness across alcoholic subgroups. Active screening for impulsive traits
      in treatment-seeking alcohol-abusing populations is recommended to improve
      treatment planning and prevent early drop-out.

PMID- 15949897
TI  - Somatization: a psychoneuroimmune perspective.
AB  - The concept of somatization has a long history in psychosomatic medicine. What is
      missing, however, is an understanding of the way patients are able to perceive
      and represent somatic symptoms. Recent advances in psychoneuroimmunology offer
      new perspectives in this area. Proinflammatory cytokines produced by cells of the
      innate immune system in response to pathogen-associated molecular patterns and to
      endogenous danger signals act on the central nervous system via afferent and
      humoral pathways to trigger a brain cytokine system that organizes the sickness
      response in its subjective, behavioral, and metabolic components. There is
      evidence that prolonged activation of this system can precipitate the development
      of depressive disorders in vulnerable patients. The mechanisms that are
      responsible for the transition from sickness to depression involve alterations in
      tryptophan metabolism. There is also some indication that the brain cytokine
      system can become sensitized in response to non-immune stressors or to immune
      stressors occurring early in life. All these new findings have the potential to
      contribute to a renewed biopsychological approach to somatization and somatoform
      disorders.

PMID- 15949899
TI  - Blue-yellow perimetry can be an early detector of hydroxychloroquine and
      chloroquine retinopathy.

PMID- 15949900
TI  - Phenytoin may increase the efficacy of temozolomide by methylating DNA-repair
      enzyme, O6-methylguanine-DNA methyltransferase in patients with glioblastoma.

PMID- 15949901
TI  - A critical review of the function of neuromelanin and an attempt to provide a
      unified theory.
AB  - This paper provides a critical review of the numerous and various biological
      functions so far attributed to neuromelanin and an attempt to provide a unified
      theory based on the peculiar physical and chemical properties of the black
      particle (the neuromelanin cage). It is stressed that neuromelanin is not
      homogeneous, as is commonly accepted, but is made up of different substrate
      specific black pigments formed by the oxidation of o.diphenols or other
      oxygenated precursors (substantia nigra melanin, locus coeruleus melanin, retinal
      pigmented epithelium or ocular melanin, inner-ear melanin, and so on). Ocular
      melanin is believed to protect the eye by trapping metals and free radicals. The
      paper shows that this unconfirmed mechanism is a rather fortuitous irreversible
      molecular accident, which at times may prove itself deleterious. Albinism often
      leads to deafness in animals, indicating a genetic correlation. These two
      conditions appear to be correlated at a molecular level to eye/ear pigmentation
      and suggest verifying this hypothesis in normal and albino human individuals.
      Skin and ocular melanin are chemically different. However, they are both involved
      in light absorption/dissipation. The black particle structure (melanin cage) is
      believed to be fundamental to this process because there is a common bioelectric
      mechanism. The latter is worth of further investigation. It is also proposed
      checking how ocular melanin dissipates the excessive absorbed light (as heat or
      as current?). It has been claimed that inner-ear melanin mutes acoustic waves.
      This paper suggests investigating the underlying mechanism and also studying
      whether this pigment is bio-electrically involved in audiology. According to
      numerous authors, substantia nigra melanin is only biological garbage. This view
      is rejected, and it is stressed that intracellular melanogenesis is a fundamental
      and genetically controlled physiological process. It has been repeatedly claimed
      that the binding of iron, heavy metals, free radicals and harmful chemicals by
      substantia nigra melanin is fundamental to body detoxification/protection.
      Presumably, such irreversible and generic binding mechanisms have no
      physiological foundation; it is suggested the alternative that, substantia nigra
      melanin acts as semiconductor, transmitting and modulating nervous impulses, in a
      reversible way. In fact, substantia nigra melanin is absent or significantly
      scarce in two conditions of life in which the coordination of movement is either
      inefficient (newborn babies) or strongly compromised (Parkinson). To check this
      assumption, further investigation of nucleus caudatus, putamen, globus pallidus,
      substantia nigra pars compacta and reticulata, nucleus hypothalamicus is
      recommended.

PMID- 15949902
TI  - Lifetime high calcium intake increases osteoporotic fracture risk in old age.
AB  - Caloric restriction prolongs life span. Calcium restriction may preserve bone
      health. In osteoporosis, bone mineral density (BMD) has significantly decreased,
      due to a lack of osteoblast bone formation. Traditional osteoporosis prevention
      is aimed at maximizing BMD, but the lifetime effects of continuously maintaining
      a high BMD on eventual bone health in old age, have not been studied. Strikingly,
      in countries with a high mean BMD, fracture rates in the elderly are
      significantly higher than in countries with a low mean BMD. Studies show that
      this is not based on genetic differences. Also, in primary hyperparathyroidism,
      on the brink of osteoporosis, BMD levels may be significantly higher than normal.
      Maybe, BMD does not represent long term bone health, but merely momentary bone
      strength. And maybe, maintaining a high BMD might actually wear out bone health.
      Since osteoporosis particularly occurs in the elderly, and because in
      osteoporotic bone less osteoblasts are available, the underlying process may have
      to do with ageing of osteoblastic cells. In healthy subjects, osteoblastic bone
      cells respond to the influx of calcium by composing a matrix upon which calcium
      precipitates. In the process of creating this matrix, 50-70% of the involved
      osteoblasts die. The greater the influx of calcium, the greater osteoblast
      activity, and the greater osteoblast apoptosis rate. An increased osteoblast
      apoptosis rate leads to a decrease in the age-related osteoblast replicative
      capacity (ARORC). In comparison to healthy bone, in osteoporotic bone the
      decrease in the replicative capacity of osteoblastic cells is greater. Due to the
      eventual resulting lack of osteoblast activity, micro-fractures cannot be
      repaired. Continuously maintaining a high BMD comes with continuously high bone
      remodeling rates, which regionally exhaust the ARORC, eventually leading to
      irreparable microfractures. Regarding long time influences on bone health,
      adequate estrogen levels are known to be protective against osteoporosis. This is
      generally attributed to its inhibiting influence on osteoclast activity. Instead,
      its net effects on osteoblast metabolism may be the key to osteoporosis
      prevention. Adequate estrogen levels inhibit osteoblast activity, calcium
      apposition and osteoblast apoptosis rate, preserving the ARORC. CONCLUSION:
      Regarding osteoporosis prevention, ARORC better than BMD represents bone health.
      Regarding ARORC, adequate estrogen levels are protective, opposing the similar
      effects of hyperparathyroidism and a high calcium diet. Tests need to be
      performed in mice to assess the lifetime effects of a high versus a low calcium
      diet, on eventual bone fracture toughness.

PMID- 15949903
TI  - In vitro and in vivo immune stimulating effects of a new standardized Echinacea
      angustifolia root extract (Polinacea).
AB  - Polinacea is a new standardized hydroethanolic extract obtained from Echinacea
      angustifolia roots containing echinacoside (>4%), the high molecular weight
      polysaccharide IDN 5405 (>5%) and a isobutylamide fraction (<0.1%). For in vitro
      tests, a bacterial lipopolysaccharide-free (LPS-free) Polinacea has been prepared
      in order to avoid non-specific responses of immunocompetent cells. LPS-free
      Polinacea enhanced the immune functions as highlighted by the proliferation rate
      and gamma-interferon production in murine T-lymphocyte cell cultures stimulated
      by anti-CD3. LPS-free Polinacea did not have a direct role on macrophage response
      as measured in the nitric oxide production test using the J774 macrophage cells
      line. In vivo, Polinacea showed an immune stimulating activity by reducing the
      Candida albicans induced mortality both in normal and in cyclosporin A-treated
      mice.

PMID- 15949904
TI  - Alternative mRNA splice forms of NOXO1: differential tissue expression and
      regulation of Nox1 and Nox3.
AB  - The activity of gp91phox, the catalytic subunit of the superoxide-generating
      respiratory burst oxidase, is stimulated by the regulatory subunits p47phox,
      p67phox and the small GTPase Rac. Novel homologs of p47phox and p67phox (NOXO1
      and NOXA1, respectively) were recently identified and are implicated in the
      regulation of the gp91phox homologs Nox1 and Nox3. Herein, we report four splice
      forms of human NOXO1. NOXO1beta is the major mRNA splice form in human colon and
      fetal liver while NOXO1gamma was the majority species in testis. Neither the
      alpha nor delta forms were expressed in significant amounts in any tissue tested.
      Splice forms were generated by alternative splicing of the two ends of exon 3 of
      the NOXO1 gene, and resulted in differences in the PX domain. The PX domain is
      known to bind inositol lipids, but the expressed, purified PX domains from
      NOXO1beta and NOXO1gamma bound these lipids with the same specificity and
      affinity. NOXO1beta and NOXO1gamma both activated Nox1, but NOXO1gamma showed a
      poorer ability to activate Nox3 compared with NOXO1beta. These data suggest
      different tissue localizations and functions for NOXO1beta and NOXO1gamma in
      regulating Nox family members.

PMID- 15949905
TI  - Iron-dependent lysosomal destabilization initiates silica-induced apoptosis in
      murine macrophages.
AB  - Alveolar macrophages play a critical role in silica-induced lung fibrosis, and
      apoptotic mechanisms have been implicated in silica-induced pathogenesis. Here,
      employing a model of murine macrophages (J774 cells), it is shown that serum
      coated alpha-quartz silica particles cause lysosomal rupture and apoptosis
      following endocytotic uptake. The loss of lysosomal integrity involves
      intralysosomal iron-catalyzed peroxidative damage to lysosomal membranes. Thus,
      lysosomal damage is most pronounced in cells exposed to silica particles with
      high amounts of surface-bound iron, whereas silica particles previously treated
      with the iron chelator desferrioxamine only induce modest rupture. Furthermore,
      inhibition of intralysosomal Fenton type chemistry, either by pre-treatment with
      desferrioxamine complexed to starch--an iron chelator targeted to the lysosomal
      compartment--or by concomitant treatment with diphenylene iodonium--a potent
      inhibitor of NADPH oxidase --both prevent silica-induced lysosomal leakage and
      ensuing apoptotic cell death. This study also demonstrates that silica-induced
      lysosomal rupture is a very early apoptotic event, preceding activation of
      caspases, disruption of transmembrane mitochondrial potential and DNA
      fragmentation. Indeed, these later apoptotic events appear to be directly
      correlated to the magnitude of lysosomal leakage, and are not observed in cells
      treated with high molecular weight desferrioxamine or diphenylene iodonium.

PMID- 15949906
TI  - Influence of lead (Pb2+) on the reactions of in vitro cultured rat aorta to 5
      hydroxytryptamine.
AB  - Although several studies demonstrated that lead induced abnormal vascular
      responses in low level lead exposed animals, investigations of the direct effects
      of lead on blood vessels are limited. In this study we tested the hypothesis that
      lead was able to directly affect the contractile reactivities of vessels. Male
      Wistar rat aortae were removed and cultured in PMRI 1640 with 1 ppm lead acetate
      for 0.5, 6, 12, 24 and 48 h, and then their responses to norepinephrine
      bitartrate (NE) and serotonin (5-hydroxytryptamine, 5-HT) were examined. The
      contractile responses to 5-HT of lead exposed aortae were significantly increased
      when the aortae were cultured for 24 and 48 h. Denudation of endothelium was able
      to abolish the increased contractile response completely. Diphenyleneiodonium
      (DPI), an inhibitor of the NAD(P)H oxidase, could abolish the increased
      contractile response to 5-HT. However, Vitamin C (VC) enhanced the contractile
      response of both groups to higher dosages of 5-HT. The expression of 5-HT(2B)
      receptor was not significantly altered by incubation with 1 ppm lead for 24 h.
      These data suggest that exposure to low levels of lead can directly increase the
      contraction of aorta to 5-HT. This effect is endothelium dependent, which is not
      mediated by increased expression of the 5-HT 2B receptor. The increased
      contraction to 5-HT may be related to increased production of superoxide (O2*-)
      induced by lead exposure.

PMID- 15949907
TI  - Induction of apoptosis in human hepatoma cells by mycelia of Antrodia camphorata
      in submerged culture.
AB  - The effect of methanolic extracts of mycelia (MEM) from Antrodia camphorata
      (Polyporaceac, Aphyllophorales) of submerged culture (ACSC) on the inhibition of
      cell viability and the mechanism of MEM-induced cytotoxic in hepatoma cells were
      investigated. The IC(50) of MEM on the cytotoxicity of HepG2 (wild type p53) and
      Hep3B (delete p53) were 49.5 and 62.7 microg/ml, respectively, on 48 h
      incubation. There is no observable cytotoxicity of MEM in Chang liver cells and
      rat primary hepatocytes at the concentration of 100 microg/ml. Cell cycle
      analysis revealed that MEM induced apoptosis on HepG2 via G0/G1 cell cycle
      arrest. MEM (100 microg/ml) treated HepG2 and Hep3B for 72 h, the apoptotic cells
      were 98.3 and 39.5%, respectively. The activities of caspase-3, -8 and -9 in
      HepG2 induced by MEM (50 microg/ml) were increased 5.3, 6.7 and 2.2-fold,
      respectively. MEM-induced apoptotic cell death was accompanied by up-regulation
      of caspase-3 and -8 in HepG2 cells. Combined treatment with MEM and caspase-3, -8
      and -9 inhibitors, the caspase-3 and -8 inhibitors were accounting for 63 and 47%
      inhibition in MEM-induced apoptosis, respectively; however, caspase-9 inhibitor
      exhibited no obvious inhibition effect on the apoptosis percentage (p>0.05). The
      results indicated that MEM induced HepG2 apoptosis through activation of caspase
      3 and -8 cascades and regulation of the cell cycle progression to inhibit
      hepatoma cells proliferation.

PMID- 15949908
TI  - Sensitive bioassay of bupivacaine in human plasma by liquid-chromatography-ion
      trap mass spectrometry.
AB  - A sensitive high-performance liquid chromatography-tandem mass spectrometric
      (HPLC-MS-MS) method, using an ion trap spectrometer, was developed for
      quantitation of bupivacaine in human plasma. Bupivacaine and an internal standard
      (ropivacaine) were extracted in a single step from 100 microL of alkalinized
      plasma with diethyl-ether. The mobile phase consisted of acetonitrile with 0.1%
      formic acid (50:50, v/v), and was delivered at a flow rate of 0.3 mL/min. The
      effluent was detected by MS-MS in positive ion mode. Ionisation was performed,
      using an electrospray ion source, operating at 200 degrees C. The selected
      reaction monitoring transitions m/z 289-->m/z 140 and m/z 275-->m/z 126 were
      chosen for bupivacaine and ropivacaine, respectively. Calibration curves were
      linear over the concentration range of 3.90-500 microg/L with determination
      coefficients >0.996. The method is accurate (bias <10%) and reproducible (intra
      assay and inter-assay precision <15%), with a quantitation limit of 3.90
      microg/L, using only 100 microL of plasma. The high specificity and sensitivity,
      achieved by this fast method (total run-time <3 min), allowed the determination
      of bupivacaine plasma levels in pediatric patients, following epidural
      administration of bupivacaine.

PMID- 15949909
TI  - Sphingomyelinase mediates macrophage activation by titanium particles independent
      of phagocytosis: a role for free radicals, NFkappaB, and TNFalpha.
AB  - The manner in which wear debris initiates intracellular signaling and macrophage
      activation remains poorly understood. While particle phagocytosis has been
      implicated in this process, recent studies have shown that phagocytosis is not
      required for macrophage activation. We examined the hypothesis that titanium
      particles stimulate macrophages through membrane associated signaling events
      involving free radicals, sphingomyelinase, NFkappaB, and TNFalpha. Titanium
      particles stimulated peroxidation of linoleic acid, producing malondialdehyde,
      while neither lipopolysaccharide nor PBS pre-incubated with particles did,
      suggesting that the increased peroxidation is related to the presence of the
      particles themselves. Furthermore, particles stimulated sphingomyelin metabolism
      in a neutral sphingomyelinase (NSmase) containing cell free system; this effect
      was inhibited by glutathione, indicating that NSmase activation was due to
      titanium induced free radicals. Titanium particles also stimulated NSmase
      activity in cultures of ANA-1 murine macrophages. Addition of purified NSmase to
      ANA-1 cell cultures stimulated NFkappaB binding, increased transcriptional
      activity in cells transfected with NFkappaB responsive promoters, and induced
      TNFalpha expression. These effects were also inhibited by addition of
      glutathione. Similarly, glutathione inhibited the ability of titanium particles
      to induce NFkappaB signaling and TNFalpha expression in ANA-1 cells. The findings
      demonstrate that titanium particles generate free radicals and induce plasma
      membrane peroxidation and NSmase activation. NSmase, in turn, hydrolyzes
      sphingomyelin, with activation of the NFkappaB signaling pathway and induction of
      responsive genes, including TNFalpha. This study demonstrates a mechanism for
      phagocytosis-independent macrophage activation and defines the sphingomyelin
      cycle as a potential therapeutic target for the prevention of wear debris induced
      osteolysis.

PMID- 15949910
TI  - [Evaluation of continuous nerve block for postoperative pain management in
      orthopaedic surgery].
AB  - OBJECTIVE: After orthopaedic surgery, continuous nerve block analgesia provides
      effective postoperative pain relief. The practical use of these techniques may
      present problems. The purpose of this study was to assess the development of
      continuous block procedure for postoperative pain based on quality standard
      management and the effectiveness of initial training as an adjunct for
      introduction of these techniques. MATERIALS AND METHODS: A staff committee of
      anaesthesiologists established a specific practical working protocol. The medical
      and paramedical teaching sessions were immediately evaluated using a
      questionnaire. RESULTS: 214 consecutive patients were included. The incidence of
      side effects and complications were higher in the beginning of protocol. Constant
      improvement of these results was observed throughout the study. The rate patients
      with pain were 10%. The analysis of medical evaluation should permit to determine
      an acceptable level of quality. Most patients were satisfied with their
      management. CONCLUSION: Pain management quality assurance program provided an
      improvement in efficacy of postoperative pain management in our protocol.
      Further, evaluation may be required to assess the complete benefits of this new
      protocol as regards postoperative pain.

PMID- 15949911
TI  - [An unusual cause of oesophageal perforation].

PMID- 15949912
TI  - [Induction of anaesthesia with target-controlled inhalation of sevoflurane in
      adults with the ZEUS anaesthesia machine].
AB  - OBJECTIVES: To evaluate if the new anaesthesia platform ZEUS (Drager Medical)
      allows the induction of anaesthesia with target-controlled inhalation of
      sevoflurane. STUDY DESIGN: Prospective clinical study. PATIENTS: Adult ASA I or
      II patients scheduled for elective surgery under general anaesthesia. METHODS:
      After preoxygenation during 3 min at 100% oxygen, patients were asked to breathe
      normally; the target end-tidal concentration of sevoflurane was fixed at 4%
      without priming of the circuit. Sufentanil (target concentration 0.5 ng/ml) was
      administered 40 s after. RESULTS: Ten patients (48+/-22 yrs) were included.
      Sevoflurane was detected in the circuit after 36+/-5 s; the target end-tidal
      concentration of sevoflurane was obtained at 130+/-19 s. Loss of consciousness
      was observed after 119+/-7 s. The induction was achieved in all patients without
      any incident. CONCLUSION: This new anaesthesia system make available the
      induction of anaesthesia with sevoflurane without priming of the circuit.

PMID- 15949913
TI  - [Faisability of foetal monitoring in prehospital care].
AB  - The use of mobile monitoring system for foetal cardiotachometry has never been
      evaluated in the prehospital care. The aim of the survey was to evaluate the
      faisability of this device. Twenty-five patients were enrolled, mostly within the
      context of interhospital transfer because of threatening premature delivery (n =
      20). Foetal monitoring was effective for 64 % of the patients during initial
      physical examination and for 52 % during transport by ambulance. Prehospital
      treatment was improved in one case of eclampsia after on-scene fetal monitoring.
      Cardiotocography can be easily performed in the prehospital setting.

PMID- 15949914
TI  - [Anthracycline-induced heart failure aggravated by pregnancy. Survival after
      cardiac assistance with artificial heart device and heart transplantation].
AB  - We report a case of a young woman suffering from a steady anthracycline-induced
      myocardiopathy with a decreased left ventricular function on echocardiography. A
      pregnancy was initiated, without worsening of the cardiopathy until 34 weeks.
      Nine days after delivery, an acute heart failure was observed leading to heart
      transplantation after cardiac assistance with heart cardiac device. As pregnancy
      is an extended stress test for a chronic failing heart, a multidisciplinary
      decision of pregnancy initiation and follow up should be preferred in pre and
      postpartum period, when such a cardiopathy exists.

PMID- 15949915
TI  - [Refractory oedema: think about systemic capillary leak syndrome].
AB  - Systemic Capillary Leak Syndrome (SCLS) is a rare and recently discovered
      disease. The diagnosis must be evoked in front of an hypovolaemic shock
      associated with a refractory anasarca. We report an observation of SCLS and then
      discuss the diagnostic and therapeutic difficulties. SCLS is diagnosed when a
      patient meet a compatible clinical situation with an hypoalbuminemia in spite of
      relative hemoconcentration. Evidence of a monoclonal gammapathy constitute an
      additional clue.

PMID- 15949917
TI  - Novel multiple 5'-amino-modified primer for DNA microarrays.
AB  - For DNA microarray analysis, total RNA is reverse-transcribed, labeled by
      incorporating fluorescent dye into the cDNA, and used to hybridize microarray.
      This protocol requires a minimum of 20 microg of total RNA. To overcome the
      sample limitation, an RNA amplification technique has been developed. Although it
      needs less RNA, this amplification technique is relatively expensive, time
      consuming, and, unfortunately, has been found to introduce bias. In this study,
      we designed a novel 5'-amino-modified primer and used it for priming cDNA
      synthesis. The novel primer has a special structure that contains four Uni-Link
      molecules with two nucleotide (thymine) residues inserted between them as
      spacers. This novel primer is used in the reverse-transcription reaction for cDNA
      synthesis. Using the novel 5'-modified primer combined with indirect labeling
      method, cDNA probes can be prepared with much less total RNA (5 microg or less)
      without amplification producing optimal results after hybridization of arrays.
      This primer can also be used to label nucleotides for other purposes.

PMID- 15949916
TI  - [Fatal outcome of an hydrogen sulfide poisoning].
AB  - We report a case of fatal outcome poisoning by massive exposure to hydrogen
      sulfide of a sewer worker. This rare event was associated with a moderate
      intoxication of two members of the rescue team. The death was due to asystole and
      massive lung oedema. Autopsy analysis showed diffuse necrotic lesions in lungs.
      Hydrogen sulfide is a direct and systemic poison, produced by organic matter
      decomposition. The direct toxicity mechanism is still unclear. The systemic
      toxicity is due to an acute toxicity by oxygen depletion at cellular level. It is
      highly diffusable and potentially very dangerous. At low concentration, rotten
      egg smell must trigger hydrogen sulfide suspicion since at higher concentration
      it is undetectable, making intoxication possible. In case of acute intoxication,
      there is an almost instantaneous cardiovascular failure and a rapid death.
      Hydrogen sulfide exposure requires prevention measures and more specifically the
      use of respiratory equipment for members of the rescue team.

PMID- 15949918
TI  - Generalized hamming networks and applications.
AB  - In this paper the classical Hamming network is generalized in various ways.
      First, for the Hamming maxnet, a generalized model is proposed, which covers
      under its umbrella most of the existing versions of the Hamming Maxnet. The
      network dynamics are time varying while the commonly used ramp function may be
      replaced by a much more general non-linear function. Also, the weight parameters
      of the network are time varying. A detailed convergence analysis is provided. A
      bound on the number of iterations required for convergence is derived and its
      distribution functions are given for the cases where the initial values of the
      nodes of the Hamming maxnet stem from the uniform and the peak distributions.
      Stabilization mechanisms aiming to prevent the node(s) with the maximum initial
      value diverging to infinity or decaying to zero are described. Simulations
      demonstrate the advantages of the proposed extension. Also, a rough comparison
      between the proposed generalized scheme as well as the original Hamming maxnet
      and its variants is carried out in terms of the time required for convergence, in
      hardware implementations. Finally, the other two parts of the Hamming network,
      namely the competitors generating module and the decoding module, are briefly
      considered in the framework of various applications such as
      classification/clustering, vector quantization and function optimization.

PMID- 15949919
TI  - Reduction in flow artifacts by using interleaved data acquisition in segmented
      balanced steady-state free precession cardiac MRI.
AB  - Balanced steady-state free precession (SSFP) magnetic resonance (MR) imaging is
      feasible for cine cardiac images because of the high contrast between myocardium
      and blood pool and robustness to rapid blood flow. Nonetheless, the flow
      artifacts are often observed because of off-resonance effects and to in-flow
      effects of the blood flow. Although reshimming the gradients or readjusting the
      center frequency reduces the artifacts, the technique can be susceptible for
      respiratory and cardiac motion and operator-dependent. The purpose of this study
      is to use another MR imaging technique for the reduction in the flow artifacts in
      the heart: odd-even interleaved data acquisition in segmented balanced SSFP
      imaging. The flow artifacts in the ventricle, ghost outside the heart, and
      visualization of the myocardial border were visually compared between sequential
      and odd-even interleaved k-space data acquisitions in cine balanced SSFP cardiac
      MR imaging. The odd-even interleaved k-space data acquisition significantly
      reduced dark flow artifacts in the left ventricle, improved the visualization of
      the myocardial border, and was easily installed. This imaging technique should be
      applied to cine segmented balanced SSFP cardiac MR imaging.

PMID- 15949920
TI  - Performance in the "real world": update on test of grocery shopping skills
      (TOGSS).

PMID- 15949921
TI  - Deramciclane in the treatment of generalized anxiety disorder: a placebo
      controlled, double-blind, dose-finding study.
AB  - Deramciclane, a camphor derivative, is a novel anxiolytic agent with a unique
      mechanism of action. It acts as a potent and specific antagonist at serotonin 5
      HT2A/2C receptors, and exhibits anxiolytic efficacy in animal models. The aim of
      this double-blind, placebo-controlled, parallel-group study was to evaluate the
      efficacy, safety, and tolerability of a range of doses of deramciclane in
      patients with generalized anxiety disorder (GAD). Adult patients with a diagnosis
      of GAD (DSM-IV) and a Hamilton Anxiety Rating Scale (HAM-A) total score >or=18; a
      score >or=2 for the HAM-A items 'Anxious Mood' and 'Tension'; a score >or=4 on
      the Clinical Global Impression of Severity of Illness (CGI-S) Scale; and a score
      <or=20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were enrolled in
      the study. Following a 1-2 week placebo run-in period, patients were randomized
      to receive deramciclane (10, 30, or 60 mg/day in two divided doses) or placebo
      for 8 weeks, followed by a 2-week placebo wash-out period. The primary efficacy
      measure was change in HAM-A score from baseline to week 8. Adverse events were
      monitored throughout the study. Withdrawal reactions were assessed at the end of
      the study (week 8) and during the placebo wash-out period using the Physician's
      Withdrawal Checklist (34 items). In the intent-to-treat population (n=208), both
      the deramciclane 30 mg/day and 60 mg/day doses provided clinically relevant
      improvements in HAM-A total score after 8 weeks of treatment, reaching
      statistical significance compared with placebo in the 60 mg/day dose group
      (p=0.024) and a clear trend in the 30 mg/day group (p=0.059). On the HAM-A
      psychic anxiety factor, significant improvements were seen in patients in the
      deramciclane 30 mg/day and 60 mg/day treatment groups compared with those in the
      placebo group (p<0.05). Adverse events were reported at a similar frequency
      across all four treatment groups; the most commonly reported adverse event was
      headache. No withdrawal reactions were observed on abrupt discontinuation of
      deramciclane. In conclusion, deramciclane 60 mg/day showed significant evidence
      of efficacy for the treatment of GAD in adult patients. The efficacy for the 30
      mg/day dose was close to the larger dose although not significant in the primary
      analysis, and there was no significant evidence of efficacy for the 10 mg/day
      dose. Deramciclane was safe and well-tolerated up to the 60 mg/day dose over an 8
      week period.

PMID- 15949922
TI  - Valproate attenuates dextroamphetamine-induced subjective changes more than
      lithium.
AB  - Dextroamphetamine administration in healthy controls produces a range of
      subjective and physiological effects, which have been likened to those occurring
      during mania. However, it is uncertain if these can be attenuated by lithium
      since conflicting results have been reported. To date there have been no previous
      studies examining the effects of valproate on dextroamphetamine-induced mood and
      physiological changes. The current study was a double-blind, placebo-controlled,
      study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg
      lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and
      physiological measures were then obtained prior to administration of a 25 mg dose
      of dextroamphetamine, and at two time points after administration. Differences in
      the response to dextroamphetamine were assessed between the three treatment
      groups. The results of this study show that pre-treatment with lithium only
      significantly attenuated dextroamphetamine-induced change in happiness, while
      valproate pre-treatment significantly attenuated the effects of dextroamphetamine
      on happiness, energy, alertness and on the diastolic blood pressure. These
      results suggest that lithium and valproate do not have the same mechanism of
      action on dextroamphetamine-induced changes, and this finding may relate to
      differences in their mechanism of action in mood disorders.

PMID- 15949923
TI  - A distinct intermediate of RNase A is induced by sodium dodecyl sulfate at its
      pK(a).
AB  - The chemical denaturation of RNase A was found to be mediated by sodium dodecyl
      sulfate (SDS) at various pH. The characterization of the unfolding pathway was
      investigated by spectrophotometry and differential scanning calorimetry (DSC),
      and was analyzed by multivariate curve resolution (MCR) as a chemometric method.
      The spectrophotometric titration curve of RNase A upon interaction with SDS
      indicated a distinct complex intermediate in glycine buffer at pH 3.3. This was
      accompanied with the catalytic activation of the enzyme and was concurrent with
      maximum population of the intermediate, determined by MCR. This was confirmed by
      the DSC profile of RNase A in the presence of SDS, indicated by two transitions
      in thermal unfolding. The kinetic data on the unfolding process of RNase A upon
      addition of SDS showed a two-phase pathway under the same conditions. The
      intermediate appeared at low pH especially at the pK(a) of SDS (pH 3.3). These
      results provide strong evidence of the influence of low pH (around the pK(a) of
      SDS) on the existence of an intermediate upon interaction of RNase A with SDS.

PMID- 15949924
TI  - Major structural proteins of type 1 and type 3 Klebsiella fimbriae are effective
      protein carriers and immunogens in conjugates as revealed from their
      immunochemical characterization.
AB  - Fimbriae are filamentous structures present on the cell surface of many bacteria,
      including genus Klebsiella. The use of fimbriae as protein carriers in conjugates
      may allow to formulate effective multivalent vaccines and suitable diagnostics.
      However, the evidences have been reported that fimbriae may enhance the
      inflammatory response. This prompted us to examine the degree of cytokine
      induction by the type 1 and type 3 Klebsiella fimbriae and their conjugates.
      Fimbriae were assessed as carrier proteins for Escherichia coli K12 endotoxin
      core oligosaccharide. MALDI-MS revealed the molecular mass of fimbrial monomer
      major protein, which was 15,847 Da for type 1 and 18,574 Da for type 3 fimbriae
      of Klebsiella. These two types of fimbriae were moderate inductors of IL-6 and
      interferon and almost inactive with regard to the stimulation of TNF when tested
      in human whole blood assay. Coupling of fimbriae with E. coli K12 core
      oligosaccharide gave immunogenic conjugates with respect to a saccharide ligand
      and protein carrier, although only 10% of the pilin monomers possessed the
      attached oligosaccharide. Rabbit antiserum reacted with a broad spectrum of
      lipopolysaccharides, as measured by ELISA and immunoblotting assays. The
      antibodies against glycoconjugates were bactericidal for the wild, S-type
      bacteria of some species. Regarding the induction of cytokines by conjugates only
      the TNF level was noticeably elevated. These results prompt for the practical use
      of fimbriae, as effective protein carriers for conjugates to obtain broad
      spectrum antisera for diagnostic applications.

PMID- 15949925
TI  - Cloning of mce1 locus of Mycobacterium leprae in Mycobacterium smegmatis mc2 155
      SMR5 and evaluation of expression of mce1 genes in M. smegmatis and M. leprae.
AB  - Plasmid pSET152 is a broad host range mobilizable vector which integrates into
      streptomyces chromosome utilizing att site and int function of slashed circleC31.
      Transformation of this plasmid into Mycobacterium smegmatis mc2 155 SMR5 gave
      stable transformants carrying the pSET152 as an integrated copy. Integration
      occurred at the cross over sequence 5'TTG disrupting the gatA gene (Glu-tRNA(Gln)
      amidotransferase subunitA), which is non-essential under conditions used.
      Recombinant pSET152 plasmids carrying mce1 locus of Mycobacterium leprae were
      used to construct M. smegmatis transformants carrying the mce1 locus in their
      chromosome. RT-PCR analysis revealed specific transcripts of M. leprae mce in M.
      smegmatis. The transcribed mRNA carried intergenic regions between genes of mce1
      locus indicating that mce1 locus is an operon. Examination of M. leprae specific
      mRNA from lepromatous leprosy patient's biopsy showed that mce locus is
      transcribed as an operon in the pathogen also.

PMID- 15949927
TI  - Identification and characterization of a novel fibronectin-binding protein gene
      from Streptococcus equi subspecies zooepidemicus strain VTU211.
AB  - This work describes the cloning and sequencing of genes encoding fibronectin
      binding proteins from Streptococcus equi subspecies zooepidemicus strain VTU211.
      A gene encoding a cell-wall protein FNZ was amplified and sequenced. In the same
      bacterial strain, a second gene termed fnz2 was now discovered, encoding another
      fibronectin-binding protein (FNZ2). The complete amino acid sequence encoded by
      fnz2 was deduced and compared to that deduced from fnz. The sequence comparison
      of the fnz and fnz2 predicted that fibronectin-binding activity is localizing a
      domain in the C terminal part of FNZ2, since this domain is composed of three
      repeats, which contain a motif similar to what has earlier been found in other
      fibronectin-binding proteins in streptococci. Three parts of fnz2 [fnz2(1-8),
      fnz2(2-4), and fnz2(4-3)] were amplified using polymerase chain reaction and
      ligated into an expression vector, and recombinant FNZ2 proteins were produced in
      Escherichia coli. Fibronectin bound to the FNZ2(1-8) [amino acids 212-396] and
      FNZ2(2-4) (amino acids 36-448) but not to the FNZ2(4-3) (amino acids 36-191) in a
      Western ligand blot, showing that repeat domain of FNZ2 protein was sufficient
      for binding of fibronectin. Purified FNZ2(2-4) protein was also shown to display
      collagen-binding activity to collagen-coated microtiter wells. These results show
      that recombinant FNZ2 has fibronectin- and collagen-binding activities.

PMID- 15949926
TI  - Expanding the bactericidal action of the food color additive phloxine B to gram
      negative bacteria.
AB  - Phloxine B (D&C red no. 28) is a color additive for food, drugs, and cosmetics.
      It has been previously shown to have anti-Staphylococcus aureus activities. In
      this work, the effect of Phloxine B on various gram-negative bacteria and other
      gram-positive bacteria including Bacillus cereus, Bacillus thuringiensis,
      Bacillus mycoides, Bacillus subtilis, Bacillus aureus, Salmonella, Escherichia
      coli and Shigella was studied, along with the mechanism of anti-microbial
      activity. In the presence of fluorescent light, the viable count for gram
      positive bacteria, (Bacillus spp. and S. aureus) decreased in a dose and time
      dependent manner when incubated with Phloxine B. The viability of gram-positive
      bacteria was reduced by 99.99% in 40 min, while there was no effect on gram
      negative bacteria (Salmonella choleraesuis, E. coli and Shigella flexneri).
      However, the use of ethylenediaminetetraacetic acid (EDTA) expands the spectrum
      of activity for Phloxine B to include gram-negative bacteria. EDTA increased
      membrane-permeability by releasing lipopolysaccharide. Overall, in an Agar
      diffusion test the light-dependent bactericidal activity of 1 microg of Phloxine
      B had a potency of 0.64 units of chloramphenicol and 0.5 units of tetracycline
      when tested on B. cereus, and had a potency of 0.7 units of chloramphenicol and
      0.2 units of tetracycline when tested on S. aureus. The data suggest that the dye
      may have some potential anti-microbial applications.

PMID- 15949929
TI  - Distinct bacterial dissemination and disease outcome in mice subcutaneously
      infected with Borrelia burgdorferi in the midline of the back and the footpad.
AB  - Subcutaneous inoculation of mice with Borrelia burgdorferi, the causative agent
      of Lyme disease, results in established infection and the development of acute
      arthritis and carditis, hallmarks of human disease. Because conflicting results
      may originate from the site of subcutaneous inoculation, we addressed the
      dissemination capacity of spirochetes injected in the shoulder region versus the
      footpad. Spirochetes inoculated in the footpad disseminated to a lesser extent to
      distant organs, such as the ear and the heart. This resulted in distinct degrees
      of joint and cardiac inflammation at the peak of the disease. The differences
      eventually leveled out. These results suggest that caution must be exercised in
      the interpretation of results obtained with routes of inoculation that do not
      closely represent the natural site of infection.

PMID- 15949928
TI  - The role of genome diversity and immune evasion in persistent infection with
      Helicobacter pylori.
AB  - Helicobacter pylori is an important human pathogen that chronically colonizes the
      stomach of half the world's population. Infection typically occurs in childhood
      and persists for decades, if not for the lifetime of the host. How is bacterial
      persistence possible despite a vigorous innate and adaptive immune response? Here
      we describe the complex role of bacterial diversity and specific mechanisms to
      avoid or subvert host immunity in bacterial persistence. We suggest that H.
      pylori finely modulates the extent to which it interacts with the host in order
      to promote chronic infection, and that it uses diverse mechanisms to do so.

PMID- 15949930
TI  - Determination of intracellular cytokines produced by Th1 and Th2 cells using flow
      cytometry in patients with brucellosis.
AB  - The aim of the study was to evaluate intracellular interferon-gamma (IFN-gamma),
      and interleukin-4 (IL-4) levels in pre- and post-treatment periods of brucellosis
      patients and to determine the relationship between these parameters and patients'
      clinical findings. Twenty-five patients diagnosed as brucellosis and 11 aged
      matched healthy volunteers were included in the study. CD3+CD4+ T lymphocytes
      levels were significantly lower in patients with brucellosis as compared to the
      control group. CD3+CD8+ T lymphocytes and CD3+IFN-gamma+ levels were increased in
      brucellosis patients compared with the control group. CD4+IFN-gamma+ and CD4+IL
      4+ levels were no different between patients and healthy individuals. CD3+IL-4+
      levels decreased in patients compared with healthy controls. Pre-treatment
      CD3+IFN-gamma+ levels dramatically increased in patients responsive to management
      compared with the unresponsive ones. In responsive cases, CD3+IFN-gamma+ levels
      decreased statistically after the treatment while in unresponsive cases no
      meaningful change was observed with respect to treatment. Adding IFN-gamma to the
      treatment for improving the depleted levels of IFN-gamma can be beneficial in
      patients with brucellosis who shows a tendency to chronicity or patients who do
      not respond to the treatment.

PMID- 15949931
TI  - Determination of two different types of cellular cementogenesis in rat molars: a
      histological and immunohistochemical study.
AB  - To elucidate the attachment mechanism of dentin and cellular cementum, developing
      and developed cellular cementum of rat molars was examined by light microscopy.
      Routine histological staining, immunohistochemical staining for bone sialoprotein
      (BSP) and osteopontin (OPN), and digestion tests with trypsin were conducted. Two
      different types of cellular cementogenesis were established, one on the mesial
      (type I cementogenesis) and one on the distal sides (type II cementogenesis) of
      the examined roots. In the type I cementogenesis a thin initial cementum layer,
      which was fibril-poor, hematoxylin-stained, and immunopositive for BSP and OPN,
      appeared on the mineralized dentin. With cellular cementogenesis, the layer
      became the cemento-dentinal junction. The cementum mineralization did not precede
      the dentin mineralization. After trypsin treatment the cemento-dentinal junction
      lost immunoreactivity for BSP and OPN and the cementum was detached from the
      dentin. In the type II cementogenesis the cellular cementum formed directly on
      the predentin without the initial cementum layer and the cementum mineralization
      preceded the dentin mineralization. Cemental and predentinal fibrils appeared to
      intermingle, as the cemento-dentinal junction was indiscernible by any staining.
      Trypsin treatment did not cause cementum detachment. The findings of the present
      study suggest that: (1) The type I cementogenesis requires the intervening
      initial cementum to bind cementum and dentin and to induce the cementum
      mineralization. (2) In the type II cementogenesis the cemento-dentinal attachment
      depends on fibril intermingling and the cementum mineralization advances apically
      and very rapidly, probably producing mineralization foci. (3) The formation of
      the initial cementum depends on the speed of the cementogenesis in the apical
      direction.

PMID- 15949933
TI  - Clinical features and airway inflammation in mild asthma versus asymptomatic
      airway hyperresponsiveness.
AB  - RATIONALE: We still do not know why some subjects with airway hyperresponsiveness
      (AHR) experience no respiratory symptoms. OBJECTIVES: Our aim was to compare
      pulmonary function, perception of bronchoconstriction, and airway inflammation in
      atopic subjects with mild recently diagnosed (<5 years, n=30) or longer-standing
      (5 years or more, n=30) symptomatic asthma in comparison with atopic subjects
      with asymptomatic AHR (n=27). METHODS: All subjects had measurements of
      expiratory flows, PC(20) methacholine, perception of breathlessness and induced
      sputum cell differential, eosinophil cationic protein and alpha(2)-macroglobulin
      levels. RESULTS: Compared with the other groups, PC(20) was significantly lower
      in longer-standing asthma and perception score for breathlessness at 20% fall in
      FEV(1) was lower in asymptomatic subjects. Markers of airway inflammation were
      similar in all groups. There were no significant correlations between sputum
      eosinophils, alpha(2)-macroglobulin and/or eosinophil cationic protein levels and
      FEV(1), FVC or PC(20) in either group. CONCLUSION: Subjects with mild asthma or
      asymptomatic AHR are similar in regard to induced sputum markers of airway
      inflammation. Although perception of bronchoconstriction was slightly lower in
      asymptomatic subjects, additional factors are probably involved to explain why
      they report no respiratory symptoms. Further studies are needed to determine why
      these last are asymptomatic.

PMID- 15949934
TI  - Disposal of solid waste in Istanbul and along the Black Sea coast of Turkey.
AB  - The increasing amount of solid waste arising from municipalities and other
      sources and its consequent disposal has been one of the major environmental
      problems in Turkey. Istanbul is a metropolitan city with a current population of
      around 14 million, and produces about 9000 ton of solid waste every day. The
      waste composition for Istanbul has changed markedly from 1981 to 1996 with large
      decreases in waste density, much of which is related to decreased amounts of ash
      collected in winter. In recent years, the Istanbul region has implemented a new
      solid waste management system with transfer stations, sanitary landfills, and
      methane recovery, which has led to major improvements. In the Black Sea region of
      Turkey, most of the municipal and industrial solid wastes, mixed with hospital
      and hazardous wastes, are dumped on the nearest lowlands and river valleys or
      into the sea. The impact of riverside and seashore dumping of solid wastes adds
      significantly to problems arising from sewage and industry on the Black Sea
      coast. Appropriate integrated solid waste management systems are needed here as
      well; however, they have been more difficult to implement than in Istanbul
      because of more difficult topography, weaker administrative structures, and the
      lower incomes of the inhabitants.

PMID- 15949932
TI  - A role for decorin in the remodeling of myocardial infarction.
AB  - Because the small leucine-rich proteoglycan decorin has been implicated in
      regulation of collagen fibrillogenesis leading to proper extracellular matrix
      assembly, we hypothesized it could play a key role in cardiac fibrosis following
      myocardial infarction. In this study we ligated the left anterior descending
      coronary artery in wildtype and decorin-null mice to produce large infarcts in
      the anterior wall of the left ventricle. At early stages post-coronary occlusion
      the myocardial infarction size did not appreciably differ between the two
      genotypes. However, we found a wider distribution of collagen fibril sizes with
      less organization and loose packing in mature scar from decorin-null mice. Thus,
      we tested the hypothesis that these abnormal collagen fibrils would adversely
      affect post-infarction mechanics and ventricular remodeling. Indeed, scar size,
      right ventricular remote hypertrophy, and left ventricular dilatation were
      greater in decorin-null animals compared with wildtype littermates 14 days after
      acute myocardial infarction. Echocardiography revealed depressed left ventricular
      systolic function between 4 and 8 weeks post-ischemia in the decorin-null
      animals. These changes indicate that decorin is required for the proper fibrotic
      evolution of myocardial infarctions, and that its absence leads to abnormal scar
      tissue formation. This might contribute to aneurysmal ventricular dilatation,
      remote hypertrophy, and depressed ventricular function.

PMID- 15949935
TI  - Classification of in-flight catering wastes in Egypt air flights and its
      potential as energy source (chemical approach).
AB  - Waste to energy conversion is based on the classification of waste. In-flight
      catering wastes resulting from Egypt Airlines economy class passengers were
      classified. The solid waste stream generated contains plastic, paper, left-over
      waste food and aluminum. The type of meal served varies according to the period
      of flight and so the quantity and content of the waste stream. It was found that
      the waste generation rate varied from 61.3 to 265 g according to the meal type.
      Breakfast snack meal generates the highest weight of waste which recorded an
      average of 265 g. Plastic waste generated varied from 39.6% to 64.6% by weight
      for the various types of meals served. A total amount of 725 tons were generated
      annually from organic waste (paper, plastic and food waste) among which a non
      combustible 39.4 tons of aluminum. The calorific value for each generated item is
      calculated and the total energy potential reached up to 14.3 TJ annually.

PMID- 15949936
TI  - Oestrogen receptor-related receptor alpha (ERRalpha) and oestrogen receptors
      (ERalpha and ERbeta) exhibit different gene expression in human colorectal tumour
      progression.
AB  - We have investigated the presence of oestrogen receptor-related (ERR) mRNA in
      human colorectal tumour tissues and adjacent normal mucosa by reverse
      transcriptase and nested-polymerase chain reaction. ERRalpha was found in 100% of
      the patients and ERRgamma in approximately 30% while ERRbeta was not detected at
      all. The multiplex PCR analysis showed elevated levels of ERRalpha mRNA in tumour
      tissue compartment as compared to normal mucosa, whereas ERRgamma mRNA was found
      in lower levels but in both tissue compartments. In contrast, oestrogen receptor
      (ERalpha and ERbeta) mRNA levels were shown to be decreased in tumour tissues. A
      positive correlation was observed between ERalpha and ERbeta and between ERalpha
      and ERRalpha, respectively, in normal mucosa but not in tumour tissue. ERRalpha
      expression in tumour tissues significantly increased from TNM stages II to IV,
      whereas both ERs progressively declined. These findings suggest that ERRalpha, as
      well as the two ERs, might play a critical role in the progression of the
      colorectal cancer.

PMID- 15949937
TI  - Involvement of both intrinsic and extrinsic pathways in IFN-gamma-induced
      apoptosis that are enhanced with cisplatin.
AB  - IFN-gamma has direct anti-proliferative effects on ovarian cancer cell lines and
      tumour cells isolated from ovarian cancer ascites. The aim of this study was to
      further elucidate the mechanisms involved. An IFN-gamma-mediated cell cycle
      blockade was detectable in synchronised cell populations. Apoptosis, which was
      caspase dependent, was also induced. When caspase activity was blocked, the anti
      proliferative effect of IFN-gamma was only partially reduced indicating
      independent roles for both growth inhibition and apoptosis in its actions. We
      have demonstrated involvement of the intrinsic apoptotic pathway; IFN-gamma
      treatment resulted in mitochondrial membrane depolarisation, cytochrome c release
      into the cytosol and activation of caspase 9. Cytochrome c release was blocked by
      the presence of a general caspase inhibitor, suggesting a role for caspases
      upstream of the mitochondria. One candidate is caspase 8, which was also
      activated in cells treated with IFN-gamma. Levels of Bid, a pro-apoptotic
      molecule that can mediate mitochondrial membrane permeabilisation when cleaved by
      caspase 8, were also decreased and indicated a potential link between these two
      pathways in IFN-gamma-induced apoptosis. Furthermore, together with cisplatin,
      IFN-gamma exerted a more powerful anti-proliferative effect.

PMID- 15949938
TI  - Removal of cadmium from aqueous system by shelled Moringa oleifera Lam. seed
      powder.
AB  - The present study explores the unexploited sorption properties of the plant
      Moringa oleifera Lam. for decontamination of Cd at laboratory scale. Sorption
      studies using standard practices were carried out in batch experiments as
      functions of biomass dosage, contact time, metal concentrations, particle size
      and pH. Percentage sorption in each case was computed on the basis of Cd
      estimation using a planar NaI (TI) detector coupled to a 4K MCA (Canberra
      Accuspec Card with PC-AT 386). The adsorption data accurately in a Freundlich
      isotherm. Sorption studies resulted in the standardization of optimum conditions
      for removal of Cd (85.10%) as follows: biomass dosage (4.0 g), metal
      concentration (25 microg/ml), contact time (40 min) and volume of the test
      solution (200 ml) at pH 6.5. Fourier transform infrared (FTIR) spectrometry
      highlighted amino acid-Cd interactions responsible for sorption phenomenon. The
      findings open up new avenues in the removal of toxic metals by shelled Moringa
      oleifera seeds (SMOS) from water bodies as low cost, domestic and environmentally
      friendly safe technology.

PMID- 15949939
TI  - Shedding light on ADAM metalloproteinases.
AB  - ADAM metalloproteinase disintegrins have emerged as the major proteinase family
      that mediates ectodomain shedding, the proteolytic release of extracellular
      domains from their membrane-bound precursors. Recent gene-manipulation studies
      have established the role of ADAM-mediated shedding in mammalian physiology and,
      in addition, raised the issue of functional redundancy among ADAM sheddases. ADAM
      sheddases activate, for example, growth factors and cytokines, thus regulating
      signalling pathways that are important in development and pathological processes
      such as cancer. The recent studies have also begun to elucidate the substrate
      specificity and the mechanisms that control ADAM-mediated shedding events that
      regulate, for example, growth-factor and Notch signalling, and the processing of
      the amyloid precursor protein.

PMID- 15949940
TI  - Module-assisted synthesis of the bifunctional labelling agent N-succinimidyl 4
      [(18)F]fluorobenzoate ([(18)F]SFB).
AB  - The three-step radiosynthesis of N-succinimidyl 4-[(18)F]fluorobenzoate
      ([(18)F]SFB) was adapted to a remotely controlled synthesis module. After
      optimization of the reaction conditions, the final [(18)F]SFB was obtained in
      decay-corrected radiochemical yields of 34-38% (related to [(18)F]fluoride; n=12)
      within a synthesis time of 68 min. The radiochemical purity was in the range of
      93-96%.

PMID- 15949942
TI  - Resection for congenital cystic adenomatoid malformation-surgery delayed is
      surgery denied?

PMID- 15949941
TI  - Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the
      cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates
      with stage of Alzheimer's-disease-related changes.
AB  - The aim of the present work was to analyze the status of metabotropic glutamate
      receptors (mGluRs) in the frontal cortex (area 8) from ten cases with common form
      DLB (cDLB) and eleven cases with pure AD in comparison with five age-matched
      controls. mGluRs, determined by radioligand binding assays, were significantly
      decreased in cerebral cortex in cDLB. This decrease was already present in cases
      with early AD changes not involving the frontal cortex, but dramatically
      correlated with AD neuropathological changes, at its greatest in isocortical
      stages, which was associated with a decrease in the expression levels of mGluR1
      detected by Western blotting. Moreover, mGluRs analyzed in pure AD were lower
      than those obtained in cDLB and also correlated with progression of illness. On
      the other hand, the expression levels of phospholipase Cbeta1 (PLCbeta1) isoform,
      which is the effector of group I mGluRs, was decreased in parallel in cDLB cases.
      Finally, the PLCbeta1 decrease was associated with reduced GTP- and l-glutamate
      stimulated PLC activity in both cDLB and AD cases. These results show that group
      I mGluRs/PLC signaling are down-regulated and desensitized in the frontal cortex
      in cDLB and AD cases and that these modifications worsen with progression of AD
      changes in the cerebral neocortex. Therefore, group I mGluR dysfunction may be
      implicated in the pathogenesis of cognitive impairment and dementia in common
      form of DLB and pure AD.

PMID- 15949943
TI  - Surgery for ischemic mitral valve prolapse.

PMID- 15949944
TI  - Awake one stage bilateral thoracoscopic sympathectomy for palmar hyperhidrosis: a
      safe outpatient procedure.
AB  - OBJECTIVE: To verify the feasibility and compare the results of thoracoscopic
      sympathectomy under local anaesthesia (LA) and spontaneous breathing vs. general
      anaesthesia (GA) with one-lung ventilation. METHODS: Two groups of consecutive
      patients underwent one stage bilateral T2-T3 thoracoscopic sympathectomy under LA
      (n=15) and GA (n=30) by the same surgical team for treatment of primary palmar
      hyperhidrosis. The groups were homogeneous for relevant demographic,
      physiological and clinical data, including pulmonary function. In both groups,
      patient's satisfaction was evaluated 24h after surgery by a simple interview and
      scored into five grades (1=very poor to 5=excellent), while quality of life (QOL)
      was evaluated by SF-36 and Nottingham's Health Profile questionnaires before and
      6 months after surgery. A cost comparison between groups concerning devices,
      drugs, global in operating room time, medical personnel and hospital stay was
      also carried out. RESULTS: No operative mortality was recorded. The overall in
      operating room time for the whole bilateral procedure under LA was 63.55+/-10.58
      vs. 86.05+/-5.75 under GA (P<0.01) and temperature increased in all patients from
      a baseline of 25.42+/-0.56 up to 32.15+/-0.84 degrees C. All patients undergone
      LA were discharged the same day after a chest roentgenogram and a short stay in
      the outpatient clinic. Among them three patients (20%) experienced a minimal
      (<30%) pneumothorax that required no treatment, while five (33.3%) had a trunk
      compensatory sweating that spontaneously resolved on the long run. Patients
      undergoing GA were discharged after a mean stay of 1.38+/-0.6 days. Among these,
      eight (26.6%) had prolonged trunk compensatory sweating that did not persist
      longer than 3 months. At a follow-up of 7.16+/-2.97 months, QOL was significantly
      improved with no difference between groups. The overall rate of satisfaction was
      greater in the LA group (P<0.05). CONCLUSIONS: In our study, awake one stage
      bilateral thoracoscopic sympathectomy for palmar hyperhidrosis could be safely
      and effectively performed as an outpatient procedure in patients refusing GA.
      Postoperative quality of life was equal to that in patients undergone the same
      procedure under GA, while patient satisfaction was better and cost were
      significantly reduced.

PMID- 15949945
TI  - A new agent for treatment of acute respiratory distress syndrome: thymoquinone.
      An experimental study in a rat model.
AB  - OBJECTIVE: Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI)
      are important clinical problems in thoracic surgery and critical care medicine.
      Most of the treatment methods are still supportive. Thymoquinone has anti
      inflammatory, spasmolytic, bronchodilator and antibacterial effects. We studied
      its effects on ALI/ARDS in a rat model. METHODS: ALI/ARDS was developed in 40
      Sprague-Dawley male rats (200-250 g in weight) by intratracheal instillation of
      human gastric juice (pH 1.2). Rats were treated with mechanic ventilator for 3h.
      There were five groups: Control group (n=11); Steroid group (n=10); Ethanol group
      (n=5); Thymoquinone group (n=9) and Thymoquinone+Steroid group (n=5). No
      instillation except gastric juice was applied in the first group. Thymoquinone
      was given in dosage of 6 mg/kg, metilprednisolone in dosage of 10mg/kg, ethanol
      0.75 ml/kg intraperitoneally (IP). Blood gas analysis and compliance measurement
      were done. At the end of the third hour, rats were sacrificed and their lungs
      were excised for histopathological examination. RESULTS: In the thymoquinone
      group, the ratio of arterial oxygen to the fraction of inspired oxygen (PO2/FiO2)
      was significantly better compared to the other groups (P=0.000-0.043). Static
      compliance measurements revealed higher values in thymoquinone and
      thymoquinone+steroid groups. Histopathological examinations showed that affected
      lung tissue is lower in groups 2 and 4 (P=0.000-0.027). CONCLUSIONS: This study
      revealed that thymoquinone improved oxygenation while both thymoquinone and
      steroids protect lung tissue from hazardous effects of human gastric juice (pH
      1.2) histopathologically.

PMID- 15949946
TI  - Spontaneous coronary artery dissection in a young woman: from emergency coronary
      artery bypass grafting to heart transplantation.
AB  - Primary spontaneous coronary artery dissection (SCAD) as cause of acute
      myocardial infarction is a rare entity with complex pathophysiology. SCAD must be
      considered every time that a healthy young patient presents an onset of acute
      myocardial ischemic syndrome or sudden death. Mostly it appears in young women
      without traditional risk factors for coronary artery disease and a significant
      proportion of them are hutted during the peripartum or early postpartum period.
      SCAD is frequently fatal and a great number of known cases have been diagnosed at
      necroscopy. The quick recognition of SCAD as cause of acute myocardial ischemia
      in a young patient is important to establish the best medical/surgical treatment
      between the different therapeutic attitudes. We describe the case occurred to a
      young low cardiac risk woman who suffered of idiopathic SCAD and was successfully
      treated by heart transplantation few days after that a conventional surgical
      myocardial revascularization had been attempted. Waiting for cardiac
      transplantation the patient survived several days, thanks to a mechanical left
      ventricular assist device (LVAD). The following hospital course was
      uncomplicated. To our knowledge, this is the second case of SCAD treated
      successfully by LVAD and orthotopic heart transplantation reported in literature.

PMID- 15949948
TI  - Cervical esophagogastric anastomosis with a new stapler in the surgery of
      esophageal carcinoma.
AB  - OBJECTIVE: A new reusable circular stapler for cervical esophagogastric
      anastomosis (CEGA) has been used to substitute the traditional method of hand
      sewn cervical anastomosis. METHODS: Over a 2-year period (09/1998-11/2000), the
      stapler was engaged on operations of 112 patients with thoracic esophageal
      carcinoma, and the anastomosis was performed through both cervical and thoracic
      incision. The operative approaches were through left thoracotomy in 85 cases, and
      through right thoracotomy in 27 cases. The results were analyzed retrospectively.
      RESULTS: All of the 112 CEGA operations were successfully performed on the
      patients who underwent esophageal resections, and no operative mortality and
      anastomotic leakage occurred. Excluding the two patients with the anastomotic
      recurrent carcinoma, anastomotic stricture occurred in 12 cases (10.9%, n=110).
      Median time to the presentation of anastomotic stricture was 4.3 months (range
      2.6-25.3 months), and the median number of dilatations was 3 (range 1-5). When
      divided into the 24 and 26 mm groups, the respective incidences of stricture were
      12.3 (7/57) and 9.4% (5/53), respectively, and the statistical results of the two
      sizes of staplers were essentially the same (P=0.6691). Eight patients
      experienced nonanastomotic-related complications (7.3%, n=110), in which there
      were three cases of recurrent laryngeal nerve injury, four cases of the left side
      pneumothorax, and one case of perforation of the proximal stomach. There was also
      a case of stapling gauze at anastomosis. Some of the complications were closely
      related to the initially improper use of the new stapler's craft. CONCLUSIONS:
      The results indicate that CEGA using the new circular stapling device in surgery
      of the esophageal carcinoma is a very effective procedure to improve the
      anastomotic technique from a traditional hand-sewn anastomosis to a stapled
      anastomosis and can reduce the incidence of complications.

PMID- 15949951
TI  - Atypical forms of isolated partial atrioventricular septal defect increase the
      risk of initial valve replacement and reoperation.
AB  - OBJECTIVE: We consider the short- and long-term outcomes of the repair of the
      isolated partial atrioventricular (AV) septal defect to determine the role played
      by the atypical forms on the initial AV valve replacement and on the risk of
      reoperation. METHODS: Two hundred and eight patients underwent an operation for
      this malformation between 1974 and 2001. Clinical and echocardiographic
      examinations were performed on all patients, the AV valve regurgitation was
      graded from 1 to 4 and a residual interatrial shunt was sought. Median age at the
      intervention was 5.8 years (3 months to 67 years). RESULTS: Median follow-up time
      was 7.5 years (range 0-22.6 years). The cumulative 30-day, 5- and 20-year
      survival rates were 96.5, 95.4 and 94.6%, respectively. AV valve replacement was
      associated with a high mortality (P<0.001). A reoperation was performed on 12
      patients (5.7%) including six patients within less than a 30-day period,
      especially to repair residual AV valve regurgitation. We performed four AV valve
      repairs by annuloplasty and six AV valve replacements. Two patients who had
      initially undergone an AV valve replacement underwent a reoperation for valve
      thrombosis. The cumulative 30-day, 5- and 20-year rates of freedom from
      reoperation were 96.5, 93.6 and 83%, respectively. An atypical form was present
      in 24 patients (11.5%) and was a risk factor for initial AV valve replacement
      (P<0.001) and for reoperation (P<0.001). A complete AV block occurred in 13
      patients (6.2%), all of them within a 30-day period. The AV valve replacement was
      a high risk factor for a complete AV block (P<0.001). At the end of our study 180
      patients (96%) were in NYHA I and 8 in NYHA II. CONCLUSIONS: The morbi-mortality
      of the isolated partial AV septal defect is primarily perioperative and is linked
      with the presence of an atypical form of the lesion. This atypical form was the
      main reason for reoperation for AV valve regurgitation. The AV valve replacement
      was associated with a high mortality and with the occurrence of complete AV
      block. Using a standardized technique, the AV septal defect can be repaired with
      excellent long-term clinical and echographic results.

PMID- 15949953
TI  - Fetal adrenal development: insight gained from adrenal tumors.
AB  - Precise and coordinated mechanisms control the growth and functional
      differentiation of fetal organ systems. Conversely, tumor progression and the
      development of cancer probably occur through a process of dysregulation and
      dedifferentiation. Similarities exist between normal human fetal adrenal cortex
      and adrenal cancers, such as high expression of growth factors, including insulin
      like growth factor II. Therefore, we might gain insight into factors involved in
      adrenocortical development through better understanding the development and
      progression of adrenocortical tumors. This review is prompted by recent gene
      profiling studies that have identified genes differentially expressed between
      normal and abnormal adrenal glands. Several of these genes are specific growth
      factors or key cell cycle regulators, in addition to genes not previously
      associated with adrenal growth or function.

PMID- 15949952
TI  - Pneumatic pulsatile ventricular assist devices in children under 1 year of age.
AB  - OBJECTIVE: Although considerable progress has been made on ventricular assist
      devices (VAD) for adults, pneumatic pulsatile circulatory support in young
      infants is still limited. There is a need for long-term ventricular assist
      devices to bridge the failing myocardium of young children until recovery or
      transplantation. Miniaturized devices and innovative modalities need to be
      optimized. We report on our experience. METHODS: From 1/1992 to 6/2004, 18
      infants (6 male/12 female) under 1 year of age were treated with the Berlin Heart
      Excor VAD. The infants were divided into two groups, depending on the year of
      treatment. Group A consists of eight infants resuscitated and supported with a
      pulsatile pneumatic ventricular assist device between 1992 and 1998 and group B
      consists of 10 infants treated between 1999 and 6/2004. With the pediatric-sized
      Berlin Heart we used miniaturized extracorporeal pneumatically driven blood
      pumps, the lowest stroke volume being 10 ml. RESULTS: In 18 children, age 3-345
      (median 147) days, artificial replacement of heart function was applied for long
      term support (1-64, median 10 days) as a life-saving measure in our hospital.
      Nine had LVAD and nine BVAD support. All were in cardiogenic shock with
      multiorgan failure; three had fulminant myocarditis, four cardiomyopathy, and one
      chronic stage of congenital heart disease. Five children were weaned from the
      system, three reached heart transplantation, and 10 died on the VAD. There were
      no differences between groups A and B regarding age, body weight or diagnosis,
      but the duration of mechanical support differed: Group A, median 2, range 1-16
      days; group B, median 12, range 1-100 days. Since 1999 (group B), the survival
      rate of our small infants has increased to 70% whereas none of the infants in
      group A survived to be discharged. CONCLUSIONS: The outcome of VAD support in
      small infants is no longer inferior to that of adult support, now optimized
      cannulas, modified anticoagulation and optimized surgical and intensive care
      management have been established.

PMID- 15949954
TI  - Access to death certificates: what should research ethics committees require for
      approval?
AB  - PURPOSE: To present and discuss the reactions of research ethics committees
      (RECs) in a number of countries when asked for approval of a study requiring
      access to death certificates to identify the physicians signing the certificates
      and to send them a four-page questionnaire about medical decisions made at the
      patient's end-of-life that could possibly have hastened death. METHODS: A simple
      questionnaire were sent to the responsible national investigator in an
      international study (Australia, Belgium, Denmark, Italy, the Netherlands, Sweden,
      Switzerland) asking about the interactions between the national research group
      and the national/regional REC(s). RESULTS: Different laws or guidelines were used
      by the RECs. Denmark, the Netherlands, and Switzerland did not require an
      application to a REC. In Australia and Sweden, the RECs wanted changes in the
      research protocol, and one national research group had to refrain from publishing
      its results because the attrition rate became too high, probably due to the
      required changes in the protocol. RECOMMENDATIONS: Generally, similar demands
      from all RECs in relation to one project are strongly desirable. In
      epidemiological research, in which voluntary completion of an anonymous
      questionnaire demonstrates consent, additional prior informed consent about being
      approached should not be required.

PMID- 15949955
TI  - Reliability and validity of self-reported male balding patterns for use in
      epidemiologic studies.
AB  - PURPOSE: To evaluate the validity and reliability of self-reported male balding
      patterns in an epidemiologic study. METHODS: Participants were 100 men 50-76
      years old who were randomly selected from a cohort study of over 77,000 men and
      women. To assess hair patterning, men selected from among 3 sets of pictures that
      best described their hair patterning at age 30, at age 45, and at their current
      age. The categories were little or no hair loss, frontal baldness, and vertex
      baldness. The self-reporting was done a second time 3 months later. An
      interviewer independently assessed each man's current hair patterning using the
      same classification scheme. RESULTS: Test-retest reliability (kappa) of self
      reported hair patterning was 0.74, 0.71, and 0.81 for age 30, age 45, and current
      age, respectively. The kappa for the comparison of the subject's report of
      current hair patterning to the interviewer's assessment was 0.47. CONCLUSION:
      Hair patterning represents a noninvasive biomarker that may be an indicator of
      increased disease risk. While trained observers may represent the gold standard,
      our study indicates that men are fairly accurate in self-reporting their balding
      patterns and are quite reliable in reporting their hair patterning at earlier
      ages.

PMID- 15949956
TI  - Protective effect of ginkgo biloba against gossypol-induced apoptosis in human
      lymphocytes.
AB  - Ginkgo biloba (EGb 761) is a well-defined plant extract that directly scavenges
      hydroxyl radicals. It is a potent antioxidant that inhibits apoptosis in cultured
      cells and is effective in treating mild-to-moderate dementia in Alzheimer
      patients. Apoptosis is an active process of cell destruction and it plays an
      important role in pathological processes. The aim of this study is to investigate
      the anti-apoptotic effect of EGb 761 in gossypol-treated human lymphocytes.
      Pretreatment of lymphocytes with 10 microg/ml EGb 761 for 30 min or 1h decreased
      the percentage of apoptosis to 17.5% and 20%, respectively. EGb 761 treatment (25
      150 microg/ml) decreased the level of apoptosis to a plateau between 8 and 10% of
      the control values. We conclude that EGb 761 reduces gossypol-induced apoptosis
      in human lymphocytes.

PMID- 15949957
TI  - Von Willebrand disease associated with superficial temporal artery
      pseudoaneurysm.
AB  - We report on two patients with von Willebrand disease (vWD) that presented with
      superficial temporal artery pseudoaneurysms following minor blunt trauma. We
      discuss the possible pathophysiological link between vWD and blood vessel
      abnormalities. The cases highlight the importance of considering the diagnosis of
      vWD in patients presenting with pseudoaneurysm.

PMID- 15949958
TI  - Implementation of outpatient treatment of deep-vein thrombosis in private
      practices in Germany.
AB  - OBJECTIVE: Implementation of outpatient treatment (OT) of deep-vein thrombosis
      (DVT) is slow despite clear evidence that it is effective, safe and cost
      efficient. DESIGN AND METHOD: An initiative was launched with the help of the
      Professional Association of Phlebologists of Germany and the industry to
      familiarize physicians in private practice who had no prior experience with OT of
      DVT. Data on quality of treatment with the low-molecular-weight heparin
      tinzaparin and phenprocoumon, compliance, clinical outcome, venous ultrasound,
      patients' satisfaction and quality of life were collected in a registry, which
      was open from July 1999 to December 2000. The results were published and their
      impact on further management of patients was assessed in second survey reported
      here. Patients of both series were followed-up clinically and with ultrasound
      over the 1st month of treatment. RESULTS: Of 67 physicians entering 827 patients
      into the registry 26 answered a questionnaire on how they treated further
      patients. Their case load had increased by 450% and data were provided on 540
      consecutive patients managed between January and June 2002. OT increased overall
      from 76 to 92%, that of popliteo-femoral DVT from 71 to 92%, and that of pelvic
      DVT from 38 to 65%. Medical reasons to decide against OT decreased from 89 to 56%
      (p<.01). Immediate leg compression was changed from bandaging to medical
      compression stockings in 20 of the 26 centres (p<.05). In total, data were
      gathered from OT of 1124 patients. No secondary hospitalisations were required
      and only one patient had a documented progression of the DVT. CONCLUSIONS: OT was
      successfully implemented in private practices through the initiative of
      individual physicians with support of the professional association and sponsoring
      by the industry-to the benefit of the providers but as much of the patients and
      their cost bearers.

PMID- 15949959
TI  - New approaches to the treatment of congenital vascular malformations (CVMs)--a
      single centre experience.
AB  - OBJECTIVE: A retrospective review of the results of management of congenital
      vascular malformation (CVM) patients was made to assess the efficacy of newly
      introduced approaches. METHODS: CVMs were categorised according to the Hamburg
      classification on the basis of minimally invasive tests. Invasive studies such as
      angiography are used to provide a road map for treatment. A new multidisciplinary
      approach was adopted, which accepts the integration of embolisation and
      sclerotherapy with traditional surgical therapy. Embolo-sclerotherapy was used as
      an independent therapy and as an adjunctive therapy to surgery. RESULTS: Ninety
      nine out of a total of 294 venous malformation patients underwent ethanol
      sclerotherapy with an immediate success rate of 98.8%, requiring 419 sessions of
      treatment. Interim results were excellent with no evidence of recurrence (mean
      follow-up 18.2 months). Most of the 25 patients treated surgically received pre
      operative embolo-sclerotherapy, each with excellent interim results and minimum
      morbidity (mean follow-up 21.2 months). Forty-eight patients among 76
      arteriovenous malformation patients underwent embolo-sclerotherapy independently
      (32/48) or adjunctively (16/48). Independent therapy on 32 produced excellent
      interim results (25/32) requiring a total of 171 sessions (mean follow-up 19.2
      months). Eighty-nine extratruncal (ET) forms of lymphatic malformations received
      multiple sessions of sclerotherapy with OK-432 (108/120 sessions) or ethanol
      (12/20 sessions). OK-432 was used in 51 paediatric patients with the ET form and
      produced an excellent response in cystic type lesions (40/45) requiring 61
      sessions with no evidence of recurrence (mean follow-up 24.2 months), whereas a
      mixed result was obtained in the cavernous type (3/6). OK-432 sclerotherapy was
      used as a pre-operative adjunctive therapy in 7 patients requiring 21 sessions
      with 17 cavernous type of the ET form, and produced good to excellent results
      after surgical excision of 14 lesions. CONCLUSION: New approaches to the
      treatment of CVMs based on a multidisciplinary approach can improve results by
      fully combined surgical treatment with embolo-sclerotherapy.

PMID- 15949960
TI  - A continuous phase-modulated approach to spatial encoding in ultrafast 2D NMR
      spectroscopy.
AB  - Ultrafast 2D NMR replaces the time-domain parametrization usually employed to
      monitor the indirect-domain spin evolution, with an equivalent encoding along a
      spatial geometry. When coupled to a gradient-assisted decoding during the
      acquisition, this enables the collection of complete 2D spectra within a single
      transient. We have presented elsewhere two strategies for carrying out the
      spatial encoding underlying ultrafast NMR: a discrete excitation protocol capable
      of imparting a phase-modulated encoding of the interactions, and a continuous
      protocol yielding amplitude-modulated signals. The former is general but has
      associated with it a number of practical complications; the latter is easier to
      implement but unsuitable for certain 2D NMR acquisitions. The present
      communication discusses a new protocol that incorporates attractive attributes
      from both alternatives, imparting a continuous spatial encoding of the
      interactions yet yielding a phase modulation of the signal. This in turn enables
      a number of basic experiments that have shown particularly useful in the context
      of in vivo 2D NMR, including 2D J-resolved and 2D H,H-COSY spectroscopies. It
      also provides a route to achieving sensitivity-enhanced acquisitions for other
      homonuclear correlation experiments, such as ultrafast 2D TOCSY. The main
      features underlying this new spatial encoding protocol are derived, and its
      potential demonstrated with a series of phase-modulated homonuclear single-scan
      2D NMR examples.

PMID- 15949961
TI  - Kinetic studies on the glutathione peroxidase activity of selenium-containing
      glutathione transferase.
AB  - Selenium-containing glutathione transferase (seleno-GST) was generated by
      biologically incorporating selenocysteine into the active site of glutathione
      transferase (GST) from a blowfly Lucilia cuprina (Diptera: Calliphoridae). Seleno
      GST mimicked the antioxidant enzyme glutathione peroxidase (GPx) and catalyzed
      the reduction of structurally different hydroperoxides by glutathione. Kinetic
      investigations reveal a ping-pong kinetic mechanism in analogy with that of the
      natural GPx cycle as opposed to the sequential one of the wild type GST. This
      difference of the mechanisms might result from the intrinsic chemical properties
      of the incorporated residue selenocysteine, and the selenium-dependent mechanism
      is suggested to contribute to enhancement of the enzymatic efficiency.

PMID- 15949962
TI  - Heterologous expression of Escherichia coli ppsA (phosphoenolpyruvate synthetase)
      and galU (UDP-glucose pyrophosphorylase) genes in Corynebacterium glutamicum, and
      its impact on trehalose synthesis.
AB  - Trehalose is a disaccharide with a wide range of applications in the food
      industry. We recently proposed a strategy for trehalose production based on a
      Corynebacterium glutamicum strain expressing the Escherichia coli enzyme UDP
      glucose pyrophosphorylase (GalU). Biochemical network analysis suggest a further
      bottleneck for trehalose synthesis resulting from the coupling of
      phosphotransferase (PTS) mediated glucose uptake, and glucose catabolism in C.
      glutamicum. To overcome this coupling, we propose the expression of E. coli
      phosphoenolpyruvate synthetase (PpsA), in addition to GalU expression, in C.
      glutamicum. Although GalU expression improved trehalose synthesis in C.
      glutamicum, the simultaneous expression of GalU and PpsA did not result in a
      further increase in trehalose yield, but resulted in an increased catabolic rate
      of glucose, which could be ascribed to the operation of a futile cycle between
      phosphoenolpyruvate and pyruvate. The impact of GalU and PpsA expression on
      polysaccharide content, side product excretion and metabolic fluxes is discussed,
      as well as alternative ways to decouple glucose uptake and catabolism, in order
      to increase trehalose yield.

PMID- 15949963
TI  - [Post-transfusion parasite transmission: do the present controls fit with the EU
      directive?].
AB  - Blood transfusion has become extremely safe regarding the transmission of
      infectious pathogens, some of them having been responsible for mostly severe
      complications and a certain loss of confidence from practitioners and patients
      over the last decades. This may result from the strict observance of ethical
      principles, of a better medical selection of donors, of technical steps for
      preparing and qualifying blood components for therapeutic use. The transfusion
      systems--which vary in their constitution and missions depending on the countries
      or even regions--have imposed themselves strict security rules and guidelines in
      industrialized countries. Further, governmental sanitary authorities have set up
      additional surveillance systems to make the transfusion systems the safest as
      possible. In addition, the Council of Europe has edicted directives to redefine
      guidelines to the preparation, use and quality assurance of blood products, that
      are mandatory in countries of the European Community. Regarding the infectious
      risks, most recommendations have focused more on the bacterial (immediate) and
      the viral (mostly delayed) risks than on the parasitic risks because these risks
      are not only less frequent in industrialized countries, but also far less well
      known and even much more complex. However, because travel habits and immigrations
      are increasing fast, most transfusion systems or blood banks must revisit their
      practices and controls towards hemoparasite transmission by blood transfusion.
      This review aims at discussing the present controls set up in most industrialized
      countries and particularly in Europe regarding the risk of post-transfusion
      transmission of hemoparasites, and the robustness of such controls as well as how
      these controls may be secured by the European Directive.

PMID- 15949964
TI  - [Primary signet ring cell carcinoma of urinary bladder. A case report].
AB  - Primary signet ring cell carcinoma of urinary bladder is a rare tumor; accounting
      for approximately 0.24% of all bladder malignancies. In this study, we report a
      case of a 58-year old man who consulted for complaints of gross hematuria, the
      bladder biopsy showed signet ring cell carcinoma; the exploration of
      gastrointestinal tract did not reveal any other tumor localizations. A total
      cystoprostatectomy was performed followed by radiotherapy. The aim of this study
      is to determine the anatomoclinical, therapy and evolution characteristics of
      this rare tumor.

PMID- 15949965
TI  - ABO blood group alleles and genetic recombination.
AB  - The ABO blood group gene is known to code for a glycosyltransferase, which acts
      at the last step of sequential extension of oligosaccharide chains attached to
      glycoproteins or glycolipids. Since the first delineation of the molecular basis
      of ABO blood group, genotype-phenotype relationship of various ABO alleles has
      been extensively studied. Major differences between the coding sequences of them
      were found to reside in exons 6 and 7. Over 70 alleles have been analyzed for
      their sequences, more than half of which were found to exhibit hybrid nature in
      their sequence motifs. These alleles seem to result not from recurrent mutation
      but most likely from intragenic recombination due to crossing-over or genetic
      conversion. Occurrence of reciprocal products and de novo recombinant support the
      idea. The aim of this article is to outline the genetic mechanism underlying the
      ABO allelic diversity with a speculative model for genesis of an allele.

PMID- 15949966
TI  - The effect of levetiracetam on levodopa induced dyskinesia in patients with
      Parkinson's disease.

PMID- 15949967
TI  - BMPs: from bone morphogenetic proteins to body morphogenetic proteins.

PMID- 15949968
TI  - Evaluation of the clastogenicity and anticlastogenicity of the carotenoid bixin
      in human lymphocyte cultures.
AB  - Carotenoids are regarded as effective antioxidants, antimutagenic and
      anticarcinogenic agents. Annatto, a red-yellow extract obtained from seeds of
      Bixa orellana L. is a mixture of several carotenoids and one of them bixin (BXN),
      is known as its major coloring compound. Studies on BXN clastogenicity and
      anticlastogenicity in cultured human lymphocytes have not been reported so far.
      Therefore, the present study was undertaken to investigate the ability of BXN to
      induce chromosomal aberrations in human lymphocytes in vitro and to examine the
      possible anticlastogenic effect of this carotenoid in chromosomal damage induced
      by the clastogen cisplatin (cDDP). Human blood samples were obtained from six
      healthy, non-smoking volunteers; two females and four males aged 18-35 years. The
      concentrations of BXN (1.0; 2.5; 5.0 or 10 microg/mL) tested in combination with
      cDDP were established on the basis of mitotic index (MI) measurements. The data
      showed that BXN was not cytotoxic or clastogenic, when compared to untreated
      control. A marked decrease in the MI values compared to the untreated control and
      an increased percentage of aberrant metaphases was seen in all cultures treated
      with cDDP. The carotenoid efficiency in reducing the inhibitory effect of cDDP on
      lymphocyte MI is concentration-dependent. Cultures simultaneously treated with
      BXN and cDDP showed a statistically significant reduction in total chromosomal
      aberrations and aberrant metaphases. In our experiments, BXN may have acted as an
      antioxidant by intercepting free radicals generated by cDDP. The data obtained in
      the present study suggest that dietary carotenoids may act as protective agents
      against clastogenic effects of antitumor agents. However, extensive studies are
      necessary to elucidate the mechanism of action of BXN before its therapeutic use.

PMID- 15949969
TI  - Positional and non-positional obstructive sleep apnea patients.

PMID- 15949970
TI  - Antimitochondrial antibodies in patients with epilepsy.
AB  - Immune mechanisms have been implicated in the pathogenesis of epilepsy. An
      increased prevalence of autoantibodies, as well as changes in serum
      immunoglobulin concentrations, has been reported in patients with epilepsy. The
      presence of unspecific antimitochondrial antibodies (AMAs) and their possible
      associations with other immunological markers were evaluated in a cohort of 1386
      adult patients with epilepsy and population-based reference subjects. Unspecific
      AMAs were more frequent in epilepsy patients than in the reference group. Thirty
      seven epilepsy patients (3.9%) and eleven control subjects (1.9%) had unspecific
      AMAs (RR 2.1, CI 1.05-4.1, P=0.03). These antibodies were associated with long
      duration of epilepsy and old age at the onset of epilepsy among patients with
      epilepsy. Their presence was independent of other immunological markers,
      comorbidity, and epilepsy medications.

PMID- 15949971
TI  - Modulation of Ah receptor and CYP1A1 expression by alpha-naphthoflavone in
      rainbow trout hepatocytes.
AB  - The objective of this study was to evaluate whether alpha-naphthoflavone (ANF)
      modulates aryl hydrocarbon receptor (AhR) signaling in rainbow trout
      (Oncorhynchus mykiss). AhR and cytochrome P450 1A1 (CYP1A1) protein and mRNA
      content were used as indictors of AhR signaling. Primary culture of rainbow trout
      hepatocytes were exposed to different concentrations of ANF (10(-9)-10(-5) M),
      while beta-naphthoflavone (BNF 10(-10)-10(-6) M) and a combination of ANF and BNF
      were used to elucidate the impact of ANF on AhR signaling. ANF increased AhR and
      CYP1A1 protein expression in a concentration-related manner; the maximal
      induction was about 50% that of BNF. Despite the differences in protein content
      between ANF and BNF stimulation, the maximal AhR and CYP1A1 mRNA abundance seen
      with the high concentrations of ANF and BNF were similar. ANF significantly
      decreased ( approximately 50%) BNF-induced AhR protein expression (only at 10(-9)
      M), but not CYP1A1 protein and gene expression. In addition, ANF at a sub-maximal
      concentration (10(-7) M) did not affect BNF-induced AhR protein content, but
      increased the sensitivity of hepatocytes to BNF-mediated CYP1A1 protein
      expression. Taken together, the mode of action of ANF appears similar to BNF,
      including modulation of AhR expression and activation of AhR-mediated signaling
      in rainbow trout hepatocytes. Overall, ANF is not only a partial AhR agonist, but
      may also modify BNF-mediated AhR signaling in trout hepatocytes.

PMID- 15949972
TI  - The modulation effects of d-amphetamine and procaine on the spontaneously
      generated action potentials in the central neuron of snail, Achatina fulica
      Ferussac.
AB  - The modulation effects of d-amphetamine and procaine on the spontaneously
      generated action potentials were studied on the RP1 central neuron of giant
      African snails (Achatina fulica Ferussac). Extra-cellular application of d
      amphetamine or procaine reversibly elicited bursts of potential (BoP). Prazosin,
      propranolol, atropine or d-tubocurarine did not alter the BoP elicited by either
      d-amphetamine or procaine. KT-5720 or H89 (protein kinase A inhibitors) blocked d
      amphetamine-elicited BoP, whereas they did not block the procaine-elicited BoP.
      U73122, neomycin (phospholipase C inhibitors) blocked the procaine-elicited BoP,
      whereas they did not block the d-amphetamine-elicited BoP in the same neuron.
      These results suggest that BoP elicited by d-amphetamine or procaine were
      associated with protein kinase A and phospholipase C activity in the neuron.

PMID- 15949973
TI  - Competitive coexistence of two Pneumocystis species.
AB  - Pneumocystis are fungal pathogens of mammalian lungs that can cause lethal
      pneumonia in immunocompromised hosts. In some mammals, coinfections of
      genetically distinct Pneumocystis populations have been identified, but the
      nature of their interaction and its significance are unknown. Two species that
      infect rats, Pneumocystis carinii and Pneumocystis wakefieldiae, were studied
      over a 6-year period, representing approximately 700 generations of Pneumocystis.
      Population densities of each species were analyzed within the framework of the
      Lotka-Volterra competition model, which revealed the two species were in
      competition and predicted competitive exclusion of one species. However, stable
      coexistence was observed in 460 replicate populations. Selected extrinsic factors
      that might mitigate the extinction were evaluated. Logistic-regression analyses
      showed that higher relative humidity and higher organism lung burdens were
      associated with infections comprised of P. carinii alone, while lower
      temperatures and an increased rat census were associated with the presence of P.
      wakefieldiae. PCR and immunofluorescent analysis of rat lung tissue showed that
      both species were present within the same alveoli, excluding habitat
      heterogeneity as a mechanism of coexistence. These data suggest that P. carinii
      and P. wakefieldiae were in competitive coexistence, which was influenced in part
      by extrinsic factors. To our knowledge, this is the first report to evaluate
      interactions of pathogenic fungal species within a mammalian host using
      ecological models.

PMID- 15949974
TI  - Contribution of the Saccharomyces cerevisiae transcriptional regulator Leu3p to
      physiology and gene expression in nitrogen- and carbon-limited chemostat
      cultures.
AB  - Transcriptional regulation of branched-chain amino-acid metabolism in
      Saccharomyces cerevisiae involves two key regulator proteins, Leu3p and Gcn4p.
      Leu3p is a pathway-specific regulator, known to regulate six genes involved in
      branched-chain amino-acid metabolism and one gene in nitrogen assimilation. Gcn4p
      is a global regulator, involved in the general response to amino-acid and purine
      starvation. To investigate the contribution of Leu3p in regulation of gene
      expression, a leu3Delta strain was compared to an isogenic reference strain using
      DNA-microarray analysis. This comparison was performed for both glucose
      grown/ammonium-limited and ethanol-limited/ammonium-excess chemostat cultures. In
      ethanol-limited cultures, absence of Leu3p led to reduced transcript levels of
      six of the seven established Leu3p target genes, but did not affect key
      physiological parameters. In ammonium-limited cultures, absence of Leu3p caused a
      drastic decrease in storage carbohydrate content. mRNA levels of genes involved
      in storage carbohydrate metabolism were also found reduced. Under N-limited
      conditions, the leu3Delta genotype elicited an amino-acid starvation response,
      leading to increased transcript levels of many amino-acid biosynthesis genes. By
      combining the transcriptome data with data from earlier studies that measured DNA
      binding of Leu3p both in vitro and in vivo, BAT1, GAT1 and OAC1 were identified
      as additional Leu3p-regulated genes. This study demonstrates that unravelling of
      transcriptional regulation networks should preferably include several cultivation
      conditions and requires a combination of experimental approaches.

PMID- 15949975
TI  - Evolutionary engineering of mixed-sugar utilization by a xylose-fermenting
      Saccharomyces cerevisiae strain.
AB  - We have recently reported about a Saccharomyces cerevisiae strain that, in
      addition to the Piromyces XylA xylose isomerase gene, overexpresses the native
      genes for the conversion of xylulose to glycolytic intermediates. This engineered
      strain (RWB 217) exhibited unprecedentedly high specific growth rates and ethanol
      production rates under anaerobic conditions with xylose as the sole carbon
      source. However, when RWB 217 was grown on glucose-xylose mixtures, a diauxic
      growth pattern was observed with a relatively slow consumption of xylose in the
      second growth phase. After prolonged cultivation in an anaerobic, xylose-limited
      chemostat, a culture with improved xylose uptake kinetics was obtained. This
      culture also exhibited improved xylose consumption in glucose-xylose mixtures. A
      further improvement in mixed-sugar utilization was obtained by prolonged
      anaerobic cultivation in automated sequencing-batch reactors on glucose-xylose
      mixtures. A final single-strain isolate (RWB 218) rapidly consumed glucose-xylose
      mixtures anaerobically, in synthetic medium, with a specific rate of xylose
      consumption exceeding 0.9 gg(-1)h(-1). When the kinetics of zero trans-influx of
      glucose and xylose of RWB 218 were compared to that of the initial strain, a
      twofold higher capacity (V(max)) as well as an improved K(m) for xylose was
      apparent in the selected strain. It is concluded that the kinetics of xylose
      fermentation are no longer a bottleneck in the industrial production of
      bioethanol with yeast.

PMID- 15949976
TI  - High-performance purification of gelsolin from plasma using anion-exchange porous
      hollow-fiber membrane.
AB  - Gelsolin was purified from bovine plasma using an anion-exchange porous hollow
      fiber membrane. The anion-change porous hollow-fiber membrane was prepared by
      radiation-induced graft polymerization of an epoxy-group-containing monomer,
      glycidyl methacrylate, and subsequent chemical modifications. Some of the epoxy
      groups of the polymer chain grafted onto the pore surface were converted into
      diethylamino groups, and the remaining epoxy groups were converted into 2
      hydroxyethylamino groups. First, a gelsolin-containing dialyzed protein solution,
      prepared by pretreatments of ammonium sulfate precipitation and dialysis of
      plasma, was forced to permeate through the pores of an anion-exchange porous
      hollow-fiber membrane. Various proteins including gelsolin were adsorbed onto the
      anion-exchange polymer brush at a high rate with negligible diffusional mass
      transfer resistance. Second, adsorbed gelsolin was specifically eluted by
      permeating 2mM calcium chloride. The amount of recovered gelsolin was 0.1 mg per
      1 mL of plasma. Third, the remaining adsorbed proteins were quantitatively eluted
      with 1M sodium chloride, leading to a constant amount of recovered gelsolin
      during four cycles of purification. The total time required for gelsolin
      purification from 30 mL of bovine plasma was 11h, during which the time for
      selective adsorption of various proteins and affinity elution of gelsolin using
      the anion-exchange porous hollow-fiber membrane was 20 min.

PMID- 15949977
TI  - Kallikrein-kinin system in inflammatory bowel diseases: Intestinal involvement
      and correlation with the degree of tissue inflammation.
AB  - BACKGROUND: Tissue kallikrein and its natural inhibitor, kallistatin, play
      opposite roles in the generation of bradykinin, a potent mediator of
      inflammation. Observations on experimental models and humans with ulcerative
      colitis suggest a pathogenetic role of the kallikrein-kinin system in
      inflammatory bowel diseases. AIM: To evaluate tissue kallikrein and kallistatin
      in intestinal tissue samples from Crohn's disease and ulcerative colitis patients
      with different degrees of disease involvement. PATIENTS AND METHODS: Full
      thickness surgical intestinal samples were obtained from 144 subjects (38 normal
      controls, 32 inflammatory controls, 38 Crohn's disease, 36 ulcerative colitis)
      and tested for kallikrein and kallistatin by immunoperoxidase techniques.
      RESULTS: Compared with controls, kallikrein immunoreactivity was significantly
      weaker in goblet cells (p=0.0001) and significantly stronger in interstitium
      (p=0.0001) of the Crohn's disease and ulcerative colitis samples. Kallistatin
      colocalised with kallikrein, with almost no reactivity in goblet cells but strong
      reactivity in interstitium of inflammatory bowel disease patients (p=0.0001
      versus controls). The kallikrein and kallistatin depletion of goblet cells and
      the increased interstitial kallikrein and kallistatin reactivity correlated with
      the degree of tissue inflammation (p=0.0001). Disease-free samples had normal
      kallikrein and kallistatin patterns. CONCLUSIONS: Kallikrein-kinin system is
      actively involved in inflammatory bowel disease as a result of the release of
      kallikrein in the intestinal extracellular space; this involvement correlates
      with the degree of tissue inflammation. The normal pattern observed in the
      disease-free samples seems to rule out a genetic defect of kallikrein and
      kallistatin in inflammatory bowel diseases.

PMID- 15949978
TI  - Antenna ring around trimeric Photosystem I in chlorophyll b containing
      cyanobacterium Prochlorothrix hollandica.
AB  - Prochlorothrix hollandica is one of the three known species of an unusual clade
      of cyanobacteria (formerly called "prochlorophytes") that contain chlorophyll a
      and b molecules bound to intrinsic light-harvesting antenna proteins. Here, we
      report the structural characterization of supramolecular complex consisting of
      Photosystem I (PSI) associated with the chlorophyll a/b-binding Pcb proteins.
      Electron microscopy and single particle image analysis of negatively stained
      preparations revealed that the Pcb-PSI supercomplex consists of a central
      trimeric PSI surrounded by a ring of 18 Pcb subunits. We conclude that the
      formation of the Pcb ring around trimeric PSI represents a mechanism for
      increasing the light-harvesting efficiency in chlorophyll b-containing
      cyanobacteria.

PMID- 15949979
TI  - Weakened coupling of conserved arginine to the proteorhodopsin chromophore and
      its counterion implies structural differences from bacteriorhodopsin.
AB  - In wild-type proteorhodopsin (pR), titration of the chromophore's counterion
      Asp(97) occurs with a pK(a) of 8.2+/-0.1. R94C mutation reduces this slightly to
      7.0+/-0.2, irrespective of treatment with ethylguanidinium. This contrasts with
      the homologous archaeal protein bacteriorhodopsin (bR), where R82C mutation was
      previously shown to elevate the pK(a) of Asp(85) by approximately 5 units, while
      reconstitution with ethylguanidinium restores it nearly to the wild-type value of
      2.5. We conclude there is much weaker electrostatic coupling between Arg(94) and
      Asp(97) in the unphotolyzed state of pR, in comparison to Arg(82) and Asp(85) in
      bR. Therefore, while fast light-driven H(+) release may depend on these two
      residues in pR as in bR, no tightly conserved pre-photolysis configuration of
      them is required.

PMID- 15949980
TI  - Transport and metabolism of D-lactate in Jerusalem artichoke mitochondria.
AB  - We report here initial studies on D-lactate metabolism in Jerusalem artichoke. It
      was found that: 1) D-lactate can be synthesized by Jerusalem artichoke by virtue
      of the presence of glyoxalase II, the activity of which was measured
      photometrically in both isolated Jerusalem artichoke mitochondria and cytosolic
      fraction after the addition of S-D-lactoyl-glutathione. 2) Externally added D
      lactate caused oxygen consumption by mitochondria, mitochondrial membrane
      potential increase and proton release, in processes that were insensitive to
      rotenone, but inhibited by both antimycin A and cyanide. 3) D-lactate was
      metabolized inside mitochondria by a flavoprotein, a putative D-lactate
      dehydrogenase, the activity of which could be measured photometrically in
      mitochondria treated with Triton X-100. 4) Jerusalem artichoke mitochondria can
      take up externally added D-lactate by means of a D-lactate/H(+) symporter
      investigated by measuring the rate of reduction of endogenous flavins. The action
      of the d-lactate translocator and of the mitochondrial D-lactate dehydrogenase
      could be responsible for the subsequent metabolism of d-lactate formed from
      methylglyoxal in the cytosol of Jerusalem artichoke.

PMID- 15949981
TI  - Divergence of the mitochondrial electron transport chains from the green alga
      Chlamydomonas reinhardtii and its colorless close relative Polytomella sp.
AB  - Compelling evidence exists that the colorless algae of the genus Polytomella
      arose from a green Chlamydomonas-like ancestor by losing its functional
      photosynthetic apparatus. Due to the close relationship between the colorless and
      the green chlorophyte, Polytomella sp. appeared as a useful indicative framework
      for structural studies of Chlamydomonas reinhardtii mitochondria. However,
      comparative studies reported here unexpectedly revealed significant differences
      between the mitochondrial respiratory systems of the two algae. Two-dimensional
      blue native/SDS-PAGE of isolated mitochondria indicated that cytochrome
      containing respiratory complexes III and IV in the two chlorophytes contrast in
      size, subunit composition and relative abundance. Complex IV in Polytomella is
      smaller than its counterpart in C. reinhardtii and occurs in two forms that
      differ presumably in the presence of subunit COXIII. The cytochrome c and the
      iron-sulfur Rieske protein of both chlorophytes revealed structural differences
      on the amino acid sequence level. Under comparable culture conditions, the
      colorless alga exhibits lower levels of cytochrome c and complex IV but a higher
      respiratory activity than the green alga. Cytochrome c levels were also found to
      be differently regulated by the growth conditions in both algae. The divergence
      between the respiratory systems in the two related chlorophytes can be viewed as
      a consequence of the loss of photosynthetic activity and/or of the adaptation to
      the environment via the acquisition of a more flexible, heterotrophic metabolism.
      Our understanding of mitochondrial function and evolution is expected to be
      greatly enhanced via further parallel studies of photosynthetic/non
      photosynthetic algae, for which this study forms an incentive.

PMID- 15949982
TI  - EPR properties of a g=2 broad signal trapped in an S1 state in Ca2+-depleted
      Photosystem II.
AB  - We investigated a new EPR signal that gives a broad line shape around g=2 in
      Ca(2+)-depleted Photosystem (PS) II. The signal was trapped by illumination at
      243 K in parallel with the formation of Y(Z)*. The ratio of the intensities
      between the g=2 broad signal and the Y(Z)* signal was 1:3, assuming a Gaussian
      line shape for the former. The g=2 broad signal and the Y(Z)* signal decayed
      together in parallel with the appearance of the S(2) state multiline at 243 K.
      The g=2 broad signal was assigned to be an intermediate S(1)X* state in the
      transition from the S(1) to the S(2) state, where X* represents an amino acid
      radical nearby manganese cluster, such as D1-His337. The signal is in thermal
      equilibrium with Y(Z)*. Possible reactions in the S state transitions in Ca(2+)
      depleted PS II were discussed.

PMID- 15949984
TI  - Function of the 23 kDa extrinsic protein of Photosystem II as a manganese binding
      protein and its role in photoactivation.
AB  - The function of the extrinsic 23 kDa protein of Photosystem II (PSII) was studied
      with respect to Mn binding and its ability to supply Mn to PSII during
      photoactivation, i.e. the light-dependent assembly of the tetramanganese cluster.
      The extrinsic proteins and the Mn cluster were removed by TRIS treatment from
      PSII-enriched membrane fragments and purified by anion exchange chromatography.
      Room temperature EPR spectra of the purified 23 kDa protein demonstrated the
      presence of Mn. Photoactivation was successful with low Mn concentrations when
      the 23 kDa protein was present, while in its absence a higher Mn concentration
      was needed to reach the same level of oxygen evolution activity. In addition, the
      rate of photoactivation was significantly accelerated in the presence of the 23
      kDa protein. It is proposed that the 23 kDa protein plays an important role in
      providing Mn during the process of PSII assembly and that it acquires Mn during
      the light-induced turnover of D1 in the PSII damage-repair cycle and delivers Mn
      to repaired PSII.

PMID- 15949983
TI  - An increase in the ATP levels occurs in cerebellar granule cells en route to
      apoptosis in which ATP derives from both oxidative phosphorylation and anaerobic
      glycolysis.
AB  - Although it is recognized that ATP plays a part in apoptosis, whether and how its
      level changes en route to apoptosis as well as how ATP is synthesized has not
      been fully investigated. We have addressed these questions using cultured
      cerebellar granule cells. In particular, we measured the content of ATP, ADP,
      AMP, IMP, inosine, adenosine and L-lactate in cells undergoing apoptosis during
      the commitment phase (0-8 h) in the absence or presence of oligomycin or/and of
      citrate, which can inhibit totally the mitochondrial oxidative phosphorylation
      and largely the substrate-level phosphorylation in glycolysis, respectively. In
      the absence of inhibitors, apoptosis was accompanied by an increase in ATP and a
      decrease in ADP with 1:1 stoichiometry, with maximum ATP level found at 3 h
      apoptosis, but with no change in levels of AMP and its breakdown products and
      with a relatively low level of L-lactate production. Consistently, there was an
      increase in the cell energy charge and in the ratio ([ATP][AMP])/[ADP](2). When
      the oxidative phosphorylation was completely blocked by oligomycin, a decrease of
      the ATP content was found both in control cells and in cells undergoing
      apoptosis, but nonetheless cells still died by apoptosis, as shown by checking
      DNA laddering and by death prevention due to actinomycin D. In this case, ATP was
      provided by anaerobic glycolysis, as suggested by the large increase of L-lactate
      production. On the other hand, citrate itself caused a small decrease in ATP
      level together with a huge decrease in L-lactate production, but it had no effect
      on cell survival. When ATP level was further decreased due to the presence of
      both oligomycin and citrate, death occurred via necrosis at 8 h, as shown by the
      lack of DNA laddering and by death prevention found due to the NMDA receptor
      antagonist MK801. However, at a longer time, when ATP level was further
      decreased, cells died neither via apoptosis nor via glutamate-dependent necrosis,
      in a manner similar to something like to energy catastrophe. Our results shows
      that cellular ATP content increases in cerebellar granule cell apoptosis, that
      the role of oxidative phosphorylation is facultative, i.e. ATP can also derive
      from anaerobic glycolysis, and that the type of cell death depends on the ATP
      availability.

PMID- 15949985
TI  - Substrate kinetics of the Acanthamoeba castellanii alternative oxidase and the
      effects of GMP.
AB  - In Acanthamoeba castellanii mitochondria, the apparent affinity values of
      alternative oxidase for oxygen were much lower than those for cytochrome c
      oxidase. For unstimulated alternative oxidase, the K(Mox) values were around 4-5
      microM both in mitochondria oxidizing 1 mM external NADH or 10 mM succinate. For
      alternative oxidase fully stimulated by 1 mM GMP, the KK(Mox) values were
      markedly different when compared to those in the absence of GMP and they varied
      when different respiratory substrates were oxidized (K(Mox) was around 1.2 microM
      for succinate and around 11 microM for NADH). Thus, with succinate as a reducing
      substrate, the activation of alternative oxidase (with GMP) resulted in the
      oxidation of the ubiquinone pool, and a corresponding decrease in K(Mox).
      However, when external NADH was oxidized, the ubiquinone pool was further reduced
      (albeit slightly) with alternative oxidase activation, and the K(Mox) increased
      dramatically. Thus, the apparent affinity of alternative oxidase for oxygen
      decreased when the ubiquinone reduction level increased either by changing the
      activator or the respiratory substrate availability.

PMID- 15949986
TI  - Control of cytochrome b6f at low and high light intensity and cyclic electron
      transport in leaves.
AB  - The light-dependent control of photosynthetic electron transport from
      plastoquinol (PQH(2)) through the cytochrome b(6)f complex (Cyt b(6)f) to
      plastocyanin (PC) and P700 (the donor pigment of Photosystem I, PSI) was
      investigated in laboratory-grown Helianthus annuus L., Nicotiana tabaccum L., and
      naturally-grown Solidago virgaurea L., Betula pendula Roth, and Tilia cordata P.
      Mill. leaves. Steady-state illumination was interrupted (light-dark transient) or
      a high-intensity 10 ms light pulse was applied to reduce PQ and oxidise PC and
      P700 (pulse-dark transient) and the following re-reduction of P700(+) and PC(+)
      was recorded as leaf transmission measured differentially at 810-950 nm. The
      signal was deconvoluted into PC(+) and P700(+) components by oxidative (far-red)
      titration (V. Oja et al., Photosynth. Res. 78 (2003) 1-15) and the PSI density
      was determined by reductive titration using single-turnover flashes (V. Oja et
      al., Biochim. Biophys. Acta 1658 (2004) 225-234). These innovations allowed the
      definition of the full light response curves of electron transport rate through
      Cyt b(6)f to the PSI donors. A significant down-regulation of Cyt b(6)f maximum
      turnover rate was discovered at low light intensities, which relaxed at medium
      light intensities, and strengthened again at saturating irradiances. We explain
      the low-light regulation of Cyt b(6)f in terms of inactivation of carbon
      reduction cycle enzymes which increases flux resistance. Cyclic electron
      transport around PSI was measured as the difference between PSI electron
      transport (determined from the light-dark transient) and PSII electron transport
      determined from chlorophyll fluorescence. Cyclic e(-) transport was not detected
      at limiting light intensities. At saturating light the cyclic electron transport
      was present in some, but not all, leaves. We explain variations in the magnitude
      of cyclic electron flow around PSI as resulting from the variable rate of non
      photosynthetic ATP-consuming processes in the chloroplast, not as a principle
      process that corrects imbalances in ATP/NADPH stoichiometry during
      photosynthesis.

PMID- 15949987
TI  - 15N-labeling to determine chlorophyll synthesis and degradation in Synechocystis
      sp. PCC 6803 strains lacking one or both photosystems.
AB  - Rates of chlorophyll synthesis and degradation were analyzed in Synechocystis sp.
      PCC 6803 wild type and mutants lacking one or both photosystems by labeling cells
      with ((15)NH(4))(2)SO(4) and Na(15)NO(3). Pigments extracted from cells were
      separated by HPLC and incorporation of the (15)N label into porphyrins was
      subsequently examined by MALDI-TOF mass spectrometry. The life time (tau) of
      chlorophyll in wild-type Synechocystis grown at a light intensity of 100 micromol
      photons m(-2) s(-1) was determined to be about 300 h, much longer than the cell
      doubling time of about 14 h. Slow chlorophyll degradation (tau approximately 200
      400 h) was also observed in Photosystem I-less and in Photosystem II-less
      Synechocystis mutants, whereas in a mutant lacking both Photosystem I and
      Photosystem II chlorophyll degradation was accelerated 4-5 fold (tau
      approximately 50 h). Chlorophyllide and pheophorbide were identified as
      intermediates of chlorophyll degradation in the Photosystem I-less/Photosystem II
      less mutant. In comparison with the wild type, the chlorophyll synthesis rate was
      five-fold slower in the Photosystem I-less strain and about eight-fold slower in
      the strain lacking both photosystems, resulting in different chlorophyll levels
      in the various mutants. The results presented in this paper demonstrate the
      presence of a regulation that adjusts the rate of chlorophyll synthesis according
      to the needs of chlorophyll-binding polypeptides associated with the
      photosystems.

PMID- 15949988
TI  - Towards elucidating the energy of the first excited singlet state of xanthophyll
      cycle pigments by X-ray absorption spectroscopy.
AB  - The first excited singlet state (S(1)) of carotenoids (also termed 2A(g)(-))
      plays a key role in photosynthetic excitation energy transfer due to its close
      proximity to the S(1) (Q(y)) level of chlorophylls. The determination of
      carotenoid 2A(g)(-) energies by optical techniques is difficult; transitions from
      the ground state (S(0), 1A(g)(-)) to the 2A(g)(-) state are forbidden ("optically
      dark") due to parity (g <-- //--> g) as well as pseudo-parity selection rules (-
      <-- //--> -). Of particular interest are S(1) energies of the so-called
      xanthophyll-cycle pigments (violaxanthin, antheraxanthin and zeaxanthin) due to
      their involvement in photoprotection in plants. Previous determinations of S(1)
      energies of violaxanthin and zeaxanthin by different spectroscopic techniques
      vary considerably. Here we present an alternative approach towards elucidation of
      the optically dark states of xanthophylls by near-edge X-ray absorption fine
      structure spectroscopy (NEXAFS). The indication of at least one pi* energy level
      (about 0.5 eV below the lowest 1B(u)(+) vibronic sublevel) has been found for
      zeaxanthin. Present limitations and future improvements of NEXAFS to study
      optically dark states of carotenoids are discussed. NEXAFS combined with
      simultaneous optical pumping will further aid the investigation of these
      otherwise hardly accessible states.

PMID- 15949989
TI  - Towards a spin coupling model for the Mn4 cluster in Photosystem II.
AB  - The X-band EPR spectra of the IR sensitive untreated PSII and of MeOH- and NH(3)
      treated PSII from spinach in the S(2)-state are simulated with collinear and
      rhombic g- and Mn-hyperfine tensors. The obtained principal values indicate a
      1Mn(III)3Mn(IV) composition for the Mn(4) cluster. The four isotropic components
      of the Mn-hyperfine tensors are found in good agreement with the previously
      published values determined from EPR and (55)Mn-ENDOR data. Assuming intrinsic
      isotropic components of the Mn-hyperfine interactions identical to those of the
      Mn-catalase, spin density values are calculated. A Y-shape 4J-coupling scheme is
      explored to reproduce the spin densities for the untreated PSII. All the required
      criteria such as a S=1/2 ground state with a low lying excited spin state (30 cm(
      1)) and an easy conversion to a S=5/2 system responsible for the g=4.1 EPR signal
      are shown to be satisfied with four antiferromagnetic interactions lying between 
      290 and -130 cm(-1).

PMID- 15949990
TI  - Attention-deficit/hyperactivity disorder: a selective overview.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a multifactorial and
      clinically heterogeneous disorder that is associated with tremendous financial
      burden, stress to families, and adverse academic and vocational outcomes.
      Attention-deficit/hyperactivity disorder is highly prevalent in children
      worldwide, and the prevalence of this disorder in adults is increasingly
      recognized. Studies of adults with a diagnosis of childhood-onset ADHD indicate
      that clinical correlates--demographic, psychosocial, psychiatric, and cognitive
      features--mirror findings among children with ADHD. Predictors of persistence of
      ADHD include family history of the disorder, psychiatric comorbidity, and
      psychosocial adversity. Family studies of ADHD have consistently supported its
      strong familial nature. Psychiatric disorders comorbid with childhood ADHD
      include oppositional defiant and conduct disorders, whereas mood and anxiety
      disorders are comorbid with ADHD in both children and adults. Pregnancy and
      delivery complications, maternal smoking during pregnancy, and adverse family
      environment variables are considered important risk factors for ADHD. The
      etiology of ADHD has not been clearly identified, although evidence supports
      neurobiologic and genetic origins. Structural and functional imaging studies
      suggest that dysfunction in the fronto-subcortical pathways, as well as
      imbalances in the dopaminergic and noradrenergic systems, contribute to the
      pathophysiology of ADHD. Medication with dopaminergic and noradrenergic activity
      seems to reduce ADHD symptoms by blocking dopamine and norepinephrine reuptake.
      Such alterations in dopaminergic and noradrenergic function are apparently
      necessary for the clinical efficacy of pharmacologic treatments of ADHD.

PMID- 15949991
TI  - Toward a new neuropsychological model of attention-deficit/hyperactivity
      disorder: subtypes and multiple deficits.

PMID- 15949992
TI  - Causal heterogeneity in attention-deficit/hyperactivity disorder: do we need
      neuropsychologically impaired subtypes?
AB  - Before assigning full etiologic validity to a psycopathologic disorder, disease
      theory suggests that a causal dysfunction in a mechanism within the affect
      individuals must be identified. Existing theories on attention
      deficit/hyperactivity disorder (ADHD) suggest such dysfunctions in cognitive,
      neuropsychological, or motivational processes in the child. To date, researchers
      have tested these theories by comparing groups with DSM-defined ADHD to children
      without ADHD. Using executive functioning as an illustration of an issue that
      exists across all such theories, this article describes substantial overlaps in
      the group performance data. Thus only a subgroup may have executive deficits.
      Noted are other supportive data suggesting multiple pathways to ADHD. The article
      explores implications and recommends that future theory and research give more
      consideration to the probability that only a subset of behaviorally defined
      children will have a deficit in a given neurocognitive mechanism believed to
      contribute to the disorder. Creation of a provisional set of criteria in DSM-V
      for defining an "executive deficit type" could stimulate research to validate the
      first etiologic subtype of ADHD and spur the development of more sophisticated
      causal models, which in the longer term may give clinicians ways to target and
      tailor treatments.

PMID- 15949993
TI  - Causal models of attention-deficit/hyperactivity disorder: from common simple
      deficits to multiple developmental pathways.
AB  - Until recently, causal models of attention-deficit/hyperactivity disorder (ADHD)
      have tended to focus on the role of common, simple, core deficits. One such model
      highlights the role of executive dysfunction due to deficient inhibitory control
      resulting from disturbances in the frontodorsal striatal circuit and associated
      mesocortical dopaminergic branches. An alternative model presents ADHD as
      resulting from impaired signaling of delayed rewards arising from disturbances in
      motivational processes, involving frontoventral striatal reward circuits and
      mesolimbic branches terminating in the ventral striatum, particularly the nucleus
      accumbens. In the present article, these models are elaborated in two ways.
      First, they are each placed within their developmental context by consideration
      of the role of person x environment correlation and interaction and individual
      adaptation to developmental constraint. Second, their relationship to one another
      is reviewed in the light of recent data suggesting that delay aversion and
      executive functions might each make distinctive contributions to the development
      of the disorder. This provides an impetus for theoretical models built around the
      idea of multiple neurodevelopmental pathways. The possibility of neuropathologic
      heterogeneity in ADHD is likely to have important implications for the clinical
      management of the condition, potentially impacting on both diagnostic strategies
      and treatment options.

PMID- 15949994
TI  - Rodent models of attention-deficit/hyperactivity disorder.
AB  - An ideal animal model should be similar to the disorder it models in terms of
      etiology, biochemistry, symptomatology, and treatment. Animal models provide
      several advantages over clinical research: simpler nervous systems, easily
      interpreted behaviors, genetic homogeneity, easily controlled environment, and a
      greater variety of interventions. Attention-deficit/hyperactivity disorder (ADHD)
      is a neurobehavioral disorder of childhood onset that is characterized by
      inattentiveness, hyperactivity, and impulsiveness. Its diagnosis is behaviorally
      based; therefore, the validation of an ADHD model must be based in behavior. An
      ADHD model must mimic the fundamental behavioral characteristics of ADHD (face
      validity), conform to a theoretical rationale for ADHD (construct validity), and
      predict aspects of ADHD behavior, genetics, and neurobiology previously uncharted
      in clinical settings (predictive validity). Spontaneously hypertensive rats (SHR)
      fulfill many of the validation criteria and compare well with clinical cases of
      ADHD. Poor performers in the five-choice serial reaction time task and Naples
      high-excitability rats (NHE) are useful models for attention-deficit disorder.
      Other animal models either focus on the less important symptom of hyperactivity
      and might be of limited value in ADHD research or are produced in ways that would
      not lead to a clinical diagnosis of ADHD in humans, even if ADHD-like behavior is
      displayed.

PMID- 15949995
TI  - Modeling attention-deficit/hyperactivity disorder: a critical appraisal of the
      cognitive-energetic model.
AB  - A number of theoretical models of attention-deficit/hyperactivity disorder (ADHD)
      have emerged in recent years that may be used as systematic guides for clinical
      research. The cognitive-energetic model (CEM) proposes that the overall
      efficiency of information processing is determined by the interplay of three
      levels: computational mechanisms of attention, state factors, and
      management/executive function (EF). The CEM encompasses both top-down and bottom
      up processes and draws attention to the fact that ADHD causes defects at all
      three levels. These include cognitive mechanisms, such as response output;
      energetic mechanisms, such as activation and effort; and management/EF deficits.
      Increasing evidence suggests that inhibition deficits associated with ADHD may,
      at least in part, be explained in terms of an energetic dysfunction. The
      activation and effort energetic pools appear most relevant to ADHD, being
      directly related to response organization; however, further testing of CEM is
      critically dependent on the development of direct measures of these energetic
      pools. The CEM is a comprehensive model of ADHD but is not without limitations.
      In particular, further research is required to define more specifically the
      relationship between process dysfunction and state dysregulation in ADHD.

PMID- 15949996
TI  - A developmental perspective on the measurement of cognitive deficits in attention
      deficit/hyperactivity disorder.
AB  - Research on the cognitive deficits associated with attention
      deficit/hyperactivity disorder has highlighted deficits in executive function in
      individuals with the disorder. This article suggests deconstructing the umbrella
      term "executive function" and focuses on one of its component processes:
      cognitive inhibition. Cognitive developmental psychology research suggests that
      component processes, such as cognitive inhibition, should be examined from a
      variety of approaches to fully appreciate patterns of competency and deficit.
      This article contrasts cognitive inhibition from behavioral inhibition and
      resistance to interference. Two types of cognitive inhibition, automatic and
      intentional, are proposed. Finally, suggestions for guiding research design are
      taken from the cognitive developmental psychology literature. These include
      studying very limited age ranges and conducting longitudinal research,
      investigating qualitative and quantitative differences in performance, examining
      the underlying processing and strategy differences between populations, and
      investigating multiple aspects of performance between populations.

PMID- 15949997
TI  - Neuroimaging and attention-deficit/hyperactivity disorder in the 21st century:
      what to consider and how to proceed.

PMID- 15949998
TI  - Structural brain imaging of attention-deficit/hyperactivity disorder.
AB  - Many investigators have hypothesized that attention-deficit/hyperactivity
      disorder (ADHD) involves structural and functional brain abnormalities in frontal
      striatal circuitry. Although our review suggests that there is substantial
      support for this hypothesis, a growing literature demonstrates widespread
      abnormalities affecting other cortical regions and the cerebellum. Because there
      is only one report studying adults with ADHD, this summary is based on children.
      A key limitation of the literature is that most of the studies until recently
      have been underpowered, using samples of fewer than 20 subjects per group.
      Nevertheless, these studies are largely consistent with the most comprehensive
      and definitive study (Castellanos et al 2002). Moreover, studies differ in the
      degree to which they address the influence of medications, comorbidities, or
      gender, and most have not addressed potentially important sources of
      heterogeneity such as family history of ADHD, subtype, or perinatal
      complications. Despite these limitations, a relatively consistent picture has
      emerged. The most replicated alterations in ADHD in childhood include
      significantly smaller volumes in the dorsolateral prefrontal cortex, caudate,
      pallidum, corpus callosum, and cerebellum. These results suggest that the brain
      is altered in a more widespread manner than has been previously hypothesized.
      Developmental studies are needed to address the evolution of this brain disorder
      into adulthood.

PMID- 15949999
TI  - Functional neuroimaging of attention-deficit/hyperactivity disorder: a review and
      suggested future directions.
AB  - Over the past few decades, functional neuroimaging techniques have begun to
      provide unprecedented windows on the neurobiology of attention
      deficit/hyperactivity disorder (ADHD) and the neural effects of medications used
      to treat the disorder. Convergent data from neuroimaging, neuropsychological,
      genetics, and neurochemical studies have implicated dysfunction of fronto
      striatal structures (lateral prefrontal cortex, dorsal anterior cingulate cortex,
      caudate, and putamen) as likely contributing to the pathophysiology of ADHD. This
      review 1) provides an overview of the main imaging techniques being used to study
      ADHD; 2) discusses their relative strengths and weaknesses, highlighting how they
      can complement one another; 3) shows how the functional imaging literature, which
      has built on the structural imaging data, is now being used to test focused
      hypotheses regarding the neurobiological substrate of ADHD; and 4) suggests
      guidelines for improving future functional imaging studies. Although at present
      there are no accepted uses for functional imaging in diagnosing ADHD, this
      article mentions possible future clinical uses of imaging in ADHD.

PMID- 15950000
TI  - The cognitive neuroscience of response inhibition: relevance for genetic research
      in attention-deficit/hyperactivity disorder.
AB  - Psychological functions that are behaviorally and neurally well specified may
      serve as endophenotypes for attention-deficit/hyperactivity disorder (ADHD)
      research. Such endophenotypes, which lie between genes and symptoms, may relate
      more directly to relevant genetic variability than does the clinical ADHD
      syndrome itself. Here we review evidence in favor of response inhibition as an
      endophenotype for ADHD research. We show that response inhibition-
      operationalized by Go/NoGo or Stop-signal tasks--requires the prefrontal cortex
      (PFC), in particular the right inferior frontal cortex (IFC); that patients with
      ADHD have significant response inhibition deficits and show altered functional
      activation and gray matter volumes in right IFC; and that a number of studies
      indicate that response inhibition performance is heritable. Additionally, we
      review evidence concerning the role of the basal ganglia in response inhibition,
      as well as the role of neuromodulatory systems. All things considered, a combined
      right IFC structure/function/response inhibition phenotype is a particularly good
      candidate for future heritability and association studies. Moreover, a dissection
      of response inhibition into more basic components such as rule maintenance,
      vigilance, and target detection may provide yet better targets for association
      with genes for neuromodulation and brain development.

PMID- 15950002
TI  - Dyslexia (specific reading disability).
AB  - Converging evidence from a number of lines of investigation indicates that
      dyslexia represents a disorder within the language system and more specifically
      within a particular subcomponent of that system, phonological processing. Recent
      advances in imaging technology, particularly the development of functional
      magnetic resonance imaging, provide evidence of a neurobiological signature for
      dyslexia, specifically a disruption of two left hemisphere posterior brain
      systems, one parieto-temporal, the other occipito-temporal, with compensatory
      engagement of anterior systems around the inferior frontal gyrus and a posterior
      (right occipito-temporal) system. Furthermore, good evidence indicates a
      computational role for the left occipito-temporal system: the development of
      fluent (automatic) reading. The brain systems for reading are malleable and their
      disruption in dyslexic children may be remediated by provision of an evidence
      based, effective reading intervention. In addition, functional magnetic resonance
      imaging studies of young adults with reading difficulties followed prospectively
      and longitudinally from age 5 through their mid twenties suggests that there may
      be two types of reading difficulties, one primarily on a genetic basis, the
      other, and far more common, reflecting environmental influences. These studies
      offer the promise for more precise identification and effective management of
      dyslexia in children, adolescents and adults.

PMID- 15950001
TI  - In vivo neuroreceptor imaging in attention-deficit/hyperactivity disorder: a
      focus on the dopamine transporter.
AB  - There is converging evidence of the role of catecholamine dysregulation in the
      underlying pathophysiology of attention-deficit/hyperactivity disorder (ADHD).
      The dopamine transporter (DAT) is known to be a key regulator of dopamine, and
      recent genetic, treatment, and imaging studies have highlighted the role of DAT
      in ADHD. There is an emerging literature on in vivo neuroreceptor imaging of DAT
      in ADHD and control subjects reported by a number of groups internationally. A
      comprehensive review of existing imaging studies of DAT binding in ADHD shows
      that six of eight independent studies by six different groups have reported
      increased DAT binding in (mostly) treatment-naive children and adults with ADHD.
      Although there is fair agreement regarding the presence and direction of abnormal
      DAT binding, there remains disagreement as to the magnitude of the finding and
      the importance of many potentially confounding variables, including clinical
      characteristics and imaging methodology. Three studies by three different groups
      have reported decreased DAT binding after methylphenidate treatment.
      Interpretation of the latter finding awaits clarification of the issue of timing
      of drug administration and imaging to disentangle receptor occupancy from
      downregulation.

PMID- 15950003
TI  - The genetics of attention-deficit/hyperactivity disorder.

PMID- 15950004
TI  - Molecular genetics of attention-deficit/hyperactivity disorder.
AB  - Results of behavioral genetic and molecular genetic studies have converged to
      suggest that both genetic and nongenetic factors contribute to the development of
      attention-deficit/hyperactivity disorder (ADHD). We review this literature, with
      a particular emphasis on molecular genetic studies. Family, twin, and adoption
      studies provide compelling evidence that genes play a strong role in mediating
      susceptibility to ADHD. This fact is most clearly seen in the 20 extant twin
      studies, which estimate the heritability of ADHD to be .76. Molecular genetic
      studies suggest that the genetic architecture of ADHD is complex. The few genome
      wide scans conducted thus far are not conclusive. In contrast, the many candidate
      gene studies of ADHD have produced substantial evidence implicating several genes
      in the etiology of the disorder. For the eight genes for which the same variant
      has been studied in three or more case-control or family-based studies, seven
      show statistically significant evidence of association with ADHD on the basis of
      the pooled odds ratio across studies: DRD4, DRD5, DAT, DBH, 5-HTT, HTR1B, and
      SNAP-25.

PMID- 15950005
TI  - Attention-deficit/hyperactivity disorder endophenotypes.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable disorder
      with a multifactorial pattern of inheritance. For complex conditions such as
      this, biologically based phenotypes that lie in the pathway from genes to
      behavior may provide a more powerful target for molecular genetic studies than
      the disorder as a whole. Although their use in ADHD is relatively new, such
      "endophenotypes" have aided the clarification of the etiology and pathophysiology
      of several other conditions in medicine and psychiatry. In this article, we
      review existing data on potential endophenotypes for ADHD, emphasizing
      neuropsychological deficits because assessment tools are cost effective and
      relatively easy to implement. Neuropsychological impairments, as well as measures
      from neuroimaging and electrophysiological paradigms, show correlations with ADHD
      and evidence of heritability, but the familial or genetic overlap between these
      constructs and ADHD remains unclear. We conclude that these endophenotypes will
      not be a quick fix for the field but offer potential if careful consideration is
      given to issues of heterogeneity, measurement and statistical power.

PMID- 15950006
TI  - Validity of the executive function theory of attention-deficit/hyperactivity
      disorder: a meta-analytic review.
AB  - One of the most prominent neuropsychologic theories of attention
      deficit/hyperactivity disorder (ADHD) suggests that its symptoms arise from a
      primary deficit in executive functions (EF), defined as neurocognitive processes
      that maintain an appropriate problem-solving set to attain a later goal. To
      examine the validity of the EF theory, we conducted a meta-analysis of 83 studies
      that administered EF measures to groups with ADHD (total N = 3734) and without
      ADHD (N = 2969). Groups with ADHD exhibited significant impairment on all EF
      tasks. Effect sizes for all measures fell in the medium range (.46-.69), but the
      strongest and most consistent effects were obtained on measures of response
      inhibition, vigilance, working memory, and planning. Weaknesses in EF were
      significant in both clinic-referred and community samples and were not explained
      by group differences in intelligence, academic achievement, or symptoms of other
      disorders. ADHD is associated with significant weaknesses in several key EF
      domains. However, moderate effect sizes and lack of universality of EF deficits
      among individuals with ADHD suggest that EF weaknesses are neither necessary nor
      sufficient to cause all cases of ADHD. Difficulties with EF appear to be one
      important component of the complex neuropsychology of ADHD.

PMID- 15950007
TI  - Statistical approaches to complex phenotypes: evaluating neuropsychological
      endophenotypes for attention-deficit/hyperactivity disorder.
AB  - There is renewed interest among psychiatric geneticists in endophenotypes,
      constructs posited to be more directly and strongly influenced by candidate genes
      than manifest disorders. Researchers have proposed various criteria for the
      selection of endophenotypes useful in finding genes that underlie psychiatric
      disorders. These criteria include the endophenotype's psychometric properties,
      its relationship to the disorder in the population and within families, its
      expression in probands' unaffected relatives, its heritability and common genetic
      influences with the disorder, its association with candidate genes that underlie
      the disorder, and its mediation and moderation of association between the
      candidate gene and the disorder. In this article, analytic methods for evaluating
      the validity and utility of putative endophenotypes consistent with these
      proposed criteria are reviewed. The use of such analyses is illustrated with data
      on childhood attention-deficit/hyperactivity disorder and time to complete Trails
      A and B from both a candidate gene study of clinically referred children and a
      study of non-referred twins. It is demonstrated that both putative endophenotypes
      show association with the dopamine D4 receptor gene and meet most (but not all)
      of the criteria proposed for their validity and utility.

PMID- 15950008
TI  - Principles of haplotype mapping and potential applications to attention
      deficit/hyperactivity disorder.
AB  - Approaches to the study of common, complex genetic disorders like attention
      deficit/hyperactivity disorder (ADHD) are evolving rapidly. Traditional linkage
      and association mapping each have distinct roles to play. Rapid advances in
      genomic information and technologies make association studies more attractive,
      including the possibility in the near future of whole genome association scans.
      This review covers the following broad topics: 1) the principles of linkage and
      association analyses as they apply to ADHD, and 2) the implications of genome
      architecture for association studies of complex diseases like ADHD. The structure
      of linkage disequilibrium is approached through review of the statistical
      measures of allelic associations and their relationship to observed haplotypes.
      The patterns of haplotypes across the human genome are discussed, as well as the
      implications of linkage disequilibrium mapping for association studies in general
      and ADHD specifically. Finally, the extent to which the allelic architecture of a
      candidate ADHD gene is publicly available and the web resources to access this
      information are covered. Today, the wealth of polymorphism data available on the
      worldwide web enables researchers to focus powerful methodologic tools on
      candidate genes and regions of interest. Coupling this with larger patient
      collections and more refined phenotyping will move forward the identification of
      disease-associated polymorphisms and ultimately the development of genetically
      based pharmaceuticals and diagnostic tests.

PMID- 15950009
TI  - Attention-deficit/hyperactivity disorder pharmacogenomics.
AB  - Although the efficacy of medications for attention-deficit/hyperactivity disorder
      (ADHD) is well demonstrated in clinical trials, substantial numbers of patients
      fail to remain on therapy, and there is tremendous variability in tolerability
      and treatment acceptance. The emerging science of pharmacogenomics seeks to
      identify patterns of genetic variation that will direct individually tailored
      treatment regimens and enhance long-term adherence. For this review, existing
      studies in ADHD pharmacogenomics were reviewed to assess current knowledge and
      provide a basis for planning future research. Twelve studies were identified. The
      majority investigated the role of candidate genes in predicting clinical response
      to methylphenidate. The most frequently studied is DAT1, although findings are
      inconsistent, with the 10-repeat polymorphism predicting both increased and
      decreased symptom reduction in various reports. Other candidates include DRD4,
      DRD5, DBH, 5HTT, SNAP-25, and COMT. One study was based on quantitative trait
      analyses in a genome-wide scan. Although interest in ADHD pharmacogenomics is
      encouraging, preliminary studies have been limited by small sample sizes,
      inconsistent research designs, retrospective reports, and a focus on symptom
      response. Future studies should emphasize large, prospective trials, assess
      multiple medications in individual subjects, and consider a full range of
      pharmacodynamic and pharmacokinetic outcomes.

PMID- 15950010
TI  - The neurobiology of attention-deficit/hyperactivity disorder.

PMID- 15950011
TI  - Neurobiology of executive functions: catecholamine influences on prefrontal
      cortical functions.
AB  - The prefrontal cortex guides behaviors, thoughts, and feelings using
      representational knowledge, i.e., working memory. These fundamental cognitive
      abilities subserve the so-called executive functions: the ability to inhibit
      inappropriate behaviors and thoughts, regulate our attention, monitor our
      actions, and plan and organize for the future. Neuropsychological and imaging
      studies indicate that these prefrontal cortex functions are weaker in patients
      with attention-deficit/hyperactivity disorder and contribute substantially to
      attention-deficit/hyperactivity disorder symptomology. Research in animals
      indicates that the prefrontal cortex is very sensitive to its neurochemical
      environment and that small changes in catecholamine modulation of prefrontal
      cortex cells can have profound effects on the ability of the prefrontal cortex to
      guide behavior. Optimal levels of norepinephrine acting at postsynaptic alpha-2A
      adrenoceptors and dopamine acting at D1 receptors are essential to prefrontal
      cortex function. Blockade of norepinephrine alpha-2-adrenoceptors in prefrontal
      cortex markedly impairs prefrontal cortex function and mimics most of the
      symptoms of attention-deficit/hyperactivity disorder, including impulsivity and
      locomotor hyperactivity. Conversely, stimulation of alpha-2-adrenoceptors in
      prefrontal cortex strengthens prefrontal cortex regulation of behavior and
      reduces distractibility. Most effective treatments for attention
      deficit/hyperactivity disorder facilitate catecholamine transmission and likely
      have their therapeutic actions by optimizing catecholamine actions in prefrontal
      cortex.

PMID- 15950012
TI  - The neuropsychopharmacology of attention-deficit/hyperactivity disorder.
AB  - More than three decades of research has attempted to elucidate the
      neuropsychopharmacology of attention-deficit/hyperactivity disorder (ADHD).
      Stimulants, a principle treatment for the disorder, act on the norepinephrine
      (NE) and dopamine (DA) systems; this has led to a long-standing hypothesis of
      catecholamine dysfunction in ADHD. Animal studies show a clear role for NE and DA
      in the modulation of executive functions, which are often disturbed in persons
      with ADHD. Nonstimulant agents that are effective in the treatment of ADHD tend
      to affect the NE system, whereas those affecting only DA, or those that affect
      neither catecholamine, are less potent in reducing ADHD symptoms. Studies of the
      effects of NE and DA peripheral metabolites by ADHD pharmacotherapies show acute
      increases in levels of these catecholamines; however, their long-term turnover
      may be reduced. Imaging studies suggest stimulants increases DA levels in the
      brain, whereas some animal models of ADHD are more consistent with excessive DA
      activation in the disorder. Ultimately, ADHD therapy may modify activity in the
      NE and DA systems to a more optimal level, thus improving responses to
      environmental stimuli and enhancing working memory and executive function.

PMID- 15950013
TI  - Stimulant actions in rodents: implications for attention-deficit/hyperactivity
      disorder treatment and potential substance abuse.
AB  - Most evidence supports the continued use of stimulants as the best available
      pharmacotherapy for the treatment of children with attention
      deficit/hyperactivity disorder (ADHD), but little is known about possible
      enduring behavioral and neuroadaptational consequences of long-term stimulant
      exposure. Although a variety of preclinical studies, particularly those using
      methylphenidate (MP), have attempted to address these issues, most of these
      studies have used procedures that might not adequately simulate clinical
      treatment conditions, and results have not been entirely consistent. In
      particular, the rationale for selection of MP doses that simulate clinical
      exposure has not been well defined. We suggest that the use of more appropriate
      treatment conditions, including doses that result in plasma drug levels
      comparable to therapeutic levels, will provide a more accurate model for
      adequately assessing the therapeutic mechanisms and potential long-term
      consequences of stimulant psychotherapy in the treatment of ADHD.

PMID- 15950014
TI  - The dopamine transporter and attention-deficit/hyperactivity disorder.
AB  - The high incidence of attention-deficit/hyperactivity disorder (ADHD) and
      escalating use of ADHD medications present a compelling case for clarifying the
      pathophysiology of, and developing laboratory or radiologic tests for, ADHD.
      Currently, the majority of specific genes implicated in ADHD encode components of
      catecholamine signaling systems. Of these, the dopamine transporter (DAT) is a
      principal target of the most widely used antihyperactivity medications
      (amphetamine and methylphenidate); the DAT gene is associated with ADHD, and some
      studies have detected abnormal levels of the DAT in brain striatum of ADHD
      subjects. Medications for ADHD interfere with dopamine transport by brain-region-
      and drug-specific mechanisms, indirectly activating dopamine- and possibly
      norepinephrine-receptor subtypes that are implicated in enhancing attention and
      experiential salience. The most commonly used DAT-selective ADHD medications
      raise extracellular dopamine levels in DAT-rich brain regions. In brain regions
      expressing both the DAT and the norepinephrine transporter (NET), the relative
      contributions of dopamine and norepinephrine to ADHD pathophysiology and
      therapeutic response are obfuscated by the capacity of the NET to clear dopamine
      as well as norepinephrine. Thus, ADHD medications targeting DAT or NET might
      disperse dopamine widely and consign dopamine storage and release to regulation
      by noradrenergic, as well as dopaminergic neurons.

PMID- 15950015
TI  - Imaging the effects of methylphenidate on brain dopamine: new model on its
      therapeutic actions for attention-deficit/hyperactivity disorder.
AB  - Methylphenidate hydrochloride (MP) is an effective treatment for attention
      deficit/hyperactivity disorder (ADHD), a common neurobehavioral disorder of
      childhood onset characterized by inattention, hyperactivity, and distractibility.
      Methylphenidate hydrochloride blocks the dopamine transporters (DAT), the main
      mechanism for removing dopamine (DA) from the synapse, is believed to be involved
      in its therapeutic properties. However, the mechanism(s) by which increases in DA
      improve symptomatology in ADHD are not completely understood. Our studies of the
      dopaminergic effects of MP in the human brain using positron emission tomography
      (PET) have shown that MP blocks DAT, and that extracellular DA increases in
      proportion to the level of blockade and the rate of DA release (modulated by DA
      cell firing). These DA increases are greater when MP is given concomitantly with
      a salient stimulus than with a neutral stimulus, documenting the context
      dependency of MP effects. Additionally, MP-induced increases in DA are associated
      with an enhanced perception of the stimulus as salient. We postulate the MP's
      therapeutic effects are due in part to its ability to enhance the magnitude of DA
      increases induced by stimuli that by themselves generate weak responses,
      enhancing their saliency and the attention and interest they elicit. We postulate
      that these effects would improve school performance.

PMID- 15950017
TI  - Neuropsychologic theory and findings in attention-deficit/hyperactivity disorder:
      the state of the field and salient challenges for the coming decade.
AB  - The past decade has witnessed the establishment of several now well-replicated
      findings in the neuropsychology of attention-deficit/hyperactivity disorder
      (ADHD), which have been confirmed by meta-analyses. Progress has been notable
      from the importing of cognitive science and neuroscience paradigms. Yet these
      findings point to many neural networks being involved in the syndrome and to
      modest effect sizes suggesting that any one neuropsychologic deficit will not be
      able to explain the disorder. In this article, leading theories and key findings
      are briefly reviewed in four key domains: attention, executive functions, state
      regulation and motivation, and temporal information processing. Key issues facing
      the field of neuropsychologic research and theory in ADHD include 1) the need for
      more integrative developmental accounts that address both multiple neural systems
      and the socialization processes that assure their development; 2) consideration
      of multiple models/measures in the same study so as to examine relative
      contributions, within-group heterogeneity, and differential deficit; and 3)
      better integration of cognitive process models with affective and temperament
      theories so that early precursors to ADHD can be better understood. Overall, the
      field has witnessed notable progress as it converges on an understanding of ADHD
      in relation to disruption of a multicomponent self-regulatory system. The next
      era must articulate multipathway, multilevel developmental accounts of ADHD that
      incorporate neuropsychologic effects.

PMID- 15950016
TI  - Varieties of attention-deficit/hyperactivity disorder-related intra-individual
      variability.
AB  - Intra-individual variability in behavior and functioning is ubiquitous among
      children with attention-deficit/hyperactivity disorder (ADHD), but it has not
      been systematically examined or integrated within causal models. This article
      seeks to provide a conceptual, methodologic, and analytic framework as a
      foundation for future research. We first identify five key research questions and
      methodologic issues. For illustration, we examine the periodic structure of
      Eriksen Flanker task reaction time (RT) data obtained from 24 boys with ADHD and
      18 age-matched comparison boys. Reaction time variability in ADHD differed
      quantitatively from control subjects, particularly at a modal frequency around
      .05 Hz (cycle length approximately 20 sec). These oscillations in RT were
      unaffected by double-blind placebo and were suppressed by double-blind
      methylphenidate. Together with converging lines of basic and clinical evidence,
      these secondary data analyses support the speculative hypothesis that the
      increased power of multisecond oscillations in ADHD RT data, and by inference, in
      attentional performance, represents a catecholaminergic deficit in the ability to
      appropriately modulate such oscillations in neuronal activity. These results
      highlight the importance of retaining time-series data and quantitatively
      examining intra-subject measures of variability as a putative endophenotype for
      ADHD.

PMID- 15950018
TI  - Attention-deficit/hyperactivity disorder in a diverse culture: do research and
      clinical findings support the notion of a cultural construct for the disorder?
AB  - There is still some debate in the literature whether Attention-Deficit
      Disorder/Hyperactivity (ADHD) is best conceptualized as a biological disorder or
      if it is best understood as a cultural construct. This review aims to contribute
      to disentangle this issue assessing clinical and research data on ADHD in a
      complete diverse culture from a developing country. We performed a systematic
      computerized review of the literature on ADHD in Brazil. All investigations were
      included if dealing with ADHD prevalence, etiology, symptomatological construct,
      or treatment. Findings were compared to those from studies in developed
      countries. The prevalence rates of ADHD (5.8% using DSM-IV criteria, 1.5% using
      ICD-10), the bi-dimensional factor construct extracted from factor analyses
      (inattention and hyperactivity/impulsivity), the pattern of ADHD comorbidity in
      clinical samples, the family genetic data suggesting a 39% family transmission in
      clinical samples and the role of some potential candidate genes in dopaminergic
      and noradrenergic systems, as well as data on the efficacy of methylphenidate in
      the disorder are all very similar to findings from developed countries. Taken
      together, these findings suggest that ADHD is not a cultural construct,
      reinforcing the importance of applying similar research methodology in different
      cultures to make findings comparable.

PMID- 15950020
TI  - Executive functions and methylphenidate response in subtypes of attention
      deficit/hyperactivity disorder.
AB  - BACKGROUND: Oculomotor tasks are a well-established means of studying executive
      functions and frontal-striatal functioning in both nonhuman primates and humans.
      Attention-deficit/hyperactivity disorder (ADHD) is thought to implicate frontal
      striatal circuitry. We used oculomotor tests to investigate executive functions
      and methylphenidate response in two subtypes of ADHD. METHODS: Subjects were
      boys, aged 11.5-14 years, with ADHD-combined (n = 10), ADHD-inattentive (n = 12),
      and control subjects (n = 10). Executive functions assessed were motor planning
      (tapped with predictive saccades), response inhibition (antisaccades), and task
      switching (saccades-antisaccades mixed). RESULTS: The ADHD-combined boys were
      impaired relative to control subjects in motor planning (p < .003) and response
      inhibition (p < .007) but not in task switching (p > .92). They were also
      significantly impaired relative to ADHD-inattentive boys, making fewer predictive
      saccades (p < .03) and having more subjects with antisaccade performance in the
      impaired range (p < .04). Methylphenidate significantly improved motor planning
      and response inhibition in both subtypes. CONCLUSIONS: ADHD-combined but not ADHD
      inattentive boys showed impairments on motor planning and response inhibition.
      These deficits might be mediated by brain structures implicated specifically in
      the hyperactive/impulsive symptoms. Methylphenidate improved oculomotor
      performance in both subtypes; thus, it was effective even when initial
      performance was not impaired.

PMID- 15950019
TI  - Patterns and predictors of attention-deficit/hyperactivity disorder persistence
      into adulthood: results from the national comorbidity survey replication.
AB  - BACKGROUND: Despite growing interest in adult attention-deficit/hyperactivity
      disorder (ADHD), little is known about predictors of persistence of childhood
      cases into adulthood. METHODS: A retrospective assessment of childhood ADHD,
      childhood risk factors, and a screen for adult ADHD were included in a sample of
      3197 18-44 year old respondents in the National Comorbidity Survey Replication
      (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to
      a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult
      persistence of childhood ADHD. Logistic regression was used to study
      retrospectively reported childhood predictors of persistence. Potential
      predictors included socio-demographics, childhood ADHD severity, childhood
      adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent
      disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS:
      Blinded clinical interviews classified 36.3% of respondents with retrospectively
      assessed childhood ADHD as meeting DSM-IV criteria for current ADHD. Childhood
      ADHD severity and childhood treatment significantly predicted persistence.
      Controlling for severity and excluding treatment, none of the other variables
      significantly predicted persistence even though they were significantly
      associated with childhood ADHD. CONCLUSIONS: No modifiable risk factors were
      found for adult persistence of ADHD. Further research, ideally based on
      prospective general population samples, is needed to search for modifiable
      determinants of adult persistence of ADHD.

PMID- 15950021
TI  - A family based study implicates solute carrier family 1-member 3 (SLC1A3) gene in
      attention-deficit/hyperactivity disorder.
AB  - BACKGROUND: The glutamatergic system, the major excitatory neurotransmitter
      system in the central nervous system (CNS) has been proposed as contributing a
      possible role in the etiology of attention deficit hyperactivity disorder (ADHD).
      This is based upon observations from animal, neuroimaging, neuroanatomical and
      neuropsychological studies. Genes related to glutamate function are therefore
      good functional candidates for this disorder. The SLC1A3 (Solute Carrier Family
      1, member 3) gene encodes a glial glutamate transporter which maps to chromosome
      5p12, a region of linkage that coincides in two published ADHD genome scans so
      far. SLC1A3 is thus both a functional and positional candidate gene for ADHD.
      METHODS: We have undertaken detailed association analysis of SLC1A3 using a multi
      stage approach for candidate gene analysis. RESULTS: In a family-based sample (n
      = 299) we found a significant association between marker rs2269272 (p = .007) and
      ADHD. Two, two-marker haplotypes, rs2269272/rs3776581 (p = .016) and
      rs2269272/rs2032893 (p = .013) also yielded evidence of association. CONCLUSIONS:
      The results of our study suggest that genetic variation in SLC1A3 may contribute
      to susceptibility to ADHD.

PMID- 15950023
TI  - Schlieren photography to study sound interaction with highly absorbing materials.
AB  - Strong absorption of sound is often caused by the conversion of sound energy into
      heat. When this happens, it is not possible to study the interaction of sound
      with the absorbing material by means of reflected sound characteristics, because
      there is no reflected sound. Detecting for example the distance that sound
      travels in a strongly absorbing material, can be done by heat detection systems.
      However, the presence of temperature detectors in such materials interferes with
      the sound field and is therefore not really suitable. Infrared measurements are a
      possible option. Another option is the use of Schlieren photography for
      simultaneous visualization of sound and heat. This technique is briefly outlined
      with a 3 MHz sound beam incident on a highly absorbing sponge.

PMID- 15950022
TI  - Clinical and diagnostic implications of lifetime attention-deficit/hyperactivity
      disorder comorbidity in adults with bipolar disorder: data from the first 1000
      STEP-BD participants.
AB  - BACKGROUND: Systematic studies of children and adolescents with a diagnosis of
      bipolar disorder show that rates of attention-deficit/hyperactivity disorder
      (ADHD) range from 60% to 90%, but the prevalence and implications of ADHD in
      adults with bipolar disorder are less clear. METHODS: The first consecutive 1000
      adults with bipolar disorder enrolled in the National Institute of Mental
      Health's Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)
      were assessed for lifetime ADHD. The retrospective course of bipolar disorder,
      current mood state, and prevalence of other comorbid psychiatric diagnoses were
      compared for the groups with and without lifetime comorbid ADHD. RESULTS: The
      overall lifetime prevalence of comorbid ADHD in this large cohort of bipolar
      patients was 9.5% (95% confidence interval 7.6%-11.4%); 14.7% of male patients
      and 5.8% of female patients with bipolar disorder had lifetime ADHD. Patients
      with bipolar disorder and ADHD had the onset of their mood disorder approximately
      5 years earlier. After adjusting for age of onset, those with ADHD comorbidity
      had shorter periods of wellness and were more frequently depressed. We found that
      patients with bipolar disorder comorbid with ADHD had a greater number of other
      comorbid psychiatric diagnoses compared with those without comorbid ADHD, with
      substantially higher rates of several anxiety disorders and alcohol and substance
      abuse and dependence. CONCLUSIONS: Lifetime ADHD is a frequent comorbid condition
      in adults with bipolar disorder, associated with a worse course of bipolar
      disorder and greater burden of other psychiatric comorbid conditions. Studies are
      needed that focus on the efficacy and safety of treating ADHD comorbid with
      bipolar disorder.

PMID- 15950024
TI  - A note on the sensitivity of SV wave scattering to surface-breaking cracks.
AB  - The results presented in this communication show that the conventional
      configuration adopting a shear vertical wave at 45 degrees of incidence to detect
      cracks breaking the surface opposite the one on which the inspecting transducer
      is placed is not optimal when the crack depth is of the order of one wavelength
      of the inspecting wave or smaller. Angles of incidence proximal to the critical
      angle of longitudinal wave should be used instead.

PMID- 15950025
TI  - Signal enhancement in Rayleigh wave interactions using a laser-ultrasound/EMAT
      imaging system.
AB  - Enhancement of signal amplitudes from Rayleigh wave interaction at solid surface
      features has been investigated when signals were detected by an in-plane
      electromagnetic acoustic transducer (EMAT). A laser-ultrasound system was used to
      inspect surface-breaking slots, serving as artificial defects. Nd:YAG laser
      pulses were delivered onto a metal surface via an optical fiber and focused to a
      line source by a cylindrical lens. An in-plane EMAT receiver detected transient
      surface acoustic waves. A-scan signals and B-scan images from surface defects
      revealed increased signal amplitude up to 2.8+/-0.3 depending on the distance of
      the transducer from a slot. An explanation is based on the interaction of the
      EMAT sensor with the Rayleigh wave. A supporting computer model was derived to
      show that experimental signal enhancements were consistent with numerical
      predictions.

PMID- 15950026
TI  - A study on a micro mover driven by ultrasonic waves.
AB  - In developing a mobile micro robot, it is important to realize an effective
      energy supply method. The existing general method is to supply energy from
      outside through a cable. However, supplying energy through a cable adds weight
      and restricts movement. Mounted energy sources, such as batteries, also add
      weight. We therefore propose a method of supplying energy to a robot externally
      without using a cable. Using the radiation of ultrasonic waves as a wave energy
      source, we devised a mover that can receive and use wave energy for propulsion.
      We investigated and clarified the movement this prototype mover through various
      experiments. Consequently, we proved the use of ultrasonic waves to be effective
      as a cable-free energy supply.

PMID- 15950027
TI  - Radial vibration characteristics of spherical piezoelectric transducers.
AB  - This paper presents the vibration characteristics of the radial mode in spherical
      piezoelectric transducers. The differential equations of piezoelectric radial
      motion have been derived in terms of radial displacement and electric potential.
      Applying mechanical and electrical boundary conditions yielded a characteristic
      equation for radial vibration. Theoretical calculations of the fundamental
      natural frequency have been compared with numerical and experimental results for
      transducers of several sizes, and have shown a good agreement. This paper
      discusses the dependence of natural frequencies on the radius and thickness of
      the piezoelectric spheres and the difference between piezoelectric and elastic
      resonances. From the results it has been concluded that the natural frequency was
      not affected for the first radial mode but was reduced by the piezoelectric
      phenomenon. It has also been concluded that the natural frequency of the first
      radial mode depended mostly on the radius rather than on the thickness of the
      sphere whereas the natural frequency of the second radial mode depended mostly on
      the thickness rather than the radius.

PMID- 15950028
TI  - Strategies for reliable automatic onset time picking of acoustic emissions and of
      ultrasound signals in concrete.
AB  - Determining the onset of transient signals like seismograms, acoustic emissions
      or ultrasound signals is very time consuming if the onset is picked manually.
      Therefore, different approaches exist, especially in seismology. The concepts of
      the most popular approaches are summarized. An own approach adapted to ultrasound
      signals and acoustic emissions, based on the Akaike Information Criterion (AIC),
      is presented. The AIC-picker is compared to an automatic onset detection
      algorithm based on the Hinkley criterion and also adapted to acoustic emissions.
      Manual picks performed by an analyst are used as reference values. Both automatic
      onset detection algorithms are applied to ultrasound signals which are used to
      monitor the setting and hardening of concrete. They are also applied to acoustic
      emissions recorded during a pull-out test. The AIC-picker produces sufficient
      reliable results for ultrasound signals where the deviation from the manual picks
      varies between 2% and 4%. Concerning acoustic emissions, only 10% of the events
      result in a mislocation vector greater than 5mm. It can be shown that our AIC
      picker is a reliable tool for automatic onset detection for ultrasound signals
      and acoustic emissions of varying signal to noise ratio.

PMID- 15950029
TI  - Acoustic measurements and computational results on material specimens with
      harmonic variation of the cross section.
AB  - The present work represents both an experimental and theoretical investigation of
      the behavior of finite cylindrical rods with harmonic variation of the cross
      section. The matrix method was used to compute the transfer power spectra of
      elastic rods with uniform circular cross section and of rods with harmonic
      variation of the cross section with distance. Theoretical and experimental
      results show that for a rod with periodical variation of the cross section, a new
      set of supplementary frequencies appear for which the transfer power coefficient
      has significant values, which are in relation with the space period of the
      inhomogeneity. Also, due to the radial component of the displacement certain
      modes are enhanced which satisfy boundary conditions on the surface and are
      obtained from the zeroes of Bessel functions.

PMID- 15950030
TI  - Lamb waves propagation in elastic plane layers with a joint strip.
AB  - The Lamb waves are used for the ultrasonic characterization of welds because of
      their relative long-range propagation. In this paper, a simplified model of a
      weld-strip between two identical semi-infinite elastic layers is investigated.
      The reflected and transmitted ultrasonic fields are expressed by modal series
      whose coefficients are obtained by application of orthogonality relation.
      Comparisons with solutions obtained by finite elements wave propagation
      simulations are made. The energy balance between the incident and the scattered
      waves is also used to verify the accuracy of the obtained modal amplitudes.

PMID- 15950031
TI  - In vitro effects of ultrasound with different energies on the conduction
      properties of neural tissue.
AB  - The effect of ultrasound at various energy levels on the conduction properties of
      neural tissue is explored in this in vitro study. Excised sciatic nerves from the
      bullfrog were used for experiments. The nerves were stimulated by 3.5 MHz
      continuous wave ultrasound at 1, 2, and 3 W for 5 min. The peak-to-peak amplitude
      of the electrically evoked compound action potential (CAP) and the conduction
      velocity (CV) were measured in the nerves before and during ultrasound
      stimulation. The CV of the nerves increased by 5-20% for ultrasound stimulations
      at 1-3 W. The CAP amplitude increased by 8% during stimulation with 1 W
      ultrasound, and progressively decreased for 2 and 3 W ultrasound. This indicates
      that the effect of lower energy ultrasound increases both the CV and the CAP
      amplitude and that the reduction in the CAP amplitude for higher energy
      ultrasound is associated largely with ultrasonic thermal effects.

PMID- 15950032
TI  - A new type of parts feeder driven by bimorph piezo actuator.
AB  - A novel meander-line structure implemented with bimorph piezoelectric actuators
      driven by two sets of alternating current power with phase difference is
      developed in this article. Via the generated traveling wave, this mechanism is
      able to transport parts. The dynamic modeling of the structure, the driving
      control circuitry design, the motion trajectory analysis and the optimal
      transport feed rate is studied, and also verified by the practical experiment.

PMID- 15950033
TI  - Lamb wave tomography of pipe-like structures.
AB  - Lamb waves are guided ultrasonic plate waves that can follow the curvature of
      pipe-like structures. By transmitting and receiving many helically propagating
      Lamb waves via longitudinal transducers in contact with the surface of a pipe,
      crosshole tomographic geometries can be mimicked and tomographic reconstructions
      performed in order to locate and size flaws. We describe here a meridional-array
      scheme which mimics a single line of transducers along the exterior surface of
      the pipe in the axial direction, and show proof of concept results on a pipe
      sample with an internal wall-thinning. We also demonstrate improved
      reconstructions for the other helical ultrasound tomography geometry where the
      transmitters and receivers lie along parallel circumferential rings. We find
      frequency compounding smoothes out some of the noise and artifacts that appear in
      the reconstructions.

PMID- 15950034
TI  - Experimental study of wave dispersion and attenuation in concrete.
AB  - Results from an experimental study concerning wave propagation in cementitious
      materials are presented in this paper. Narrow band pulses at several frequencies
      were introduced into specimens of cement paste, mortar and concrete allowing
      direct measurement of longitudinal wave velocities and amplitude for each
      frequency. It is shown that aggregate content play an important role in wave
      propagation increasing considerably the wave velocity, while the aggregate size
      seems to control the attenuation observed. Slight velocity variations observed
      with frequency are discussed in relation to the degree of inhomogeneity of the
      materials.

PMID- 15950035
TI  - Stability analysis of the rotor of ultrasonic motor driving fluid directly.
AB  - The stability of the rotor of ultrasonic motor driving fluid directly is a key to
      its applications and control. This paper introduced the acoustic streaming and
      acoustic viscous stress near the boundary layer. Following this, the effect of
      acoustic viscous force on the stability of the rotor of ultrasonic motor driving
      fluid directly was presented in detail. The result showed that this system can be
      equivalent to a mass-spring and the spring constant can be used to weigh the
      stability of the rotor. By this model and relevant experiments, factors that
      affect the stability of the rotor such as the driving frequency, the rotor's
      weight and radius, the saturated acoustic streaming velocity, the mode number of
      stator vibration, the fluid's height and type are investigated and useful
      guidelines for design and application are obtained.

PMID- 15950036
TI  - The exceedance patterns of air quality criteria: a case study of ozone and
      nitrogen dioxide in Seoul, Korea between 1990 and 2000.
AB  - In this study, the environmental behavior of two major airborne pollutants, ozone
      and nitrogen dioxide, was investigated with respect to their exceedance patterns
      of air quality criteria. For this purpose, we used data sets collected from a
      total of 31 air quality monitoring stations dispersed across the Seoul
      metropolitan city between 1990 and 2000. In the case of NO(2), the frequency of
      hourly exceedance data sets exhibited little changes in the early 90s. However,
      it increased dramatically after 1995, probably in compliance with a rapid
      increase in the total number of automobiles. Likewise, the daily exceedance of
      O(3) in the early 90s was not significant, approaching 100 cases (except in
      1994). However, its total quantity began to surpass 300 cases since around 1996.
      Comparison of those exceedance data was also made among spatially divided data
      groups. In the case of NO(2), the occurrence of exceedance data was dominated by
      the western part of the city in both magnitude and frequency. On the other hand,
      that for O(3) was characterized by notably strong occurrences in the eastern
      counterpart. The overall results of our analysis of the NO(2) and O(3) exceedance
      data sets indicate an inextricable linkage between the two pollutants in
      association with geographical and meteorological factors.

PMID- 15950037
TI  - Copper complexing properties of dissolved organic materials exuded by the
      freshwater microalgae Scenedesmus acuminatus (Chlorophyceae).
AB  - Dissolved organic materials released by the freshwater microalgae Scenedesmus
      acuminatus were fractionated into low- and high-molecular weight materials, which
      were investigated for their capacity to bind copper. The high-molecular weight
      material was also investigated for its monosaccharide composition and is further
      discussed in relation to the copper binding property. S. acuminatus was grown in
      batch cultures under laboratory controlled conditions and harvested at the
      beginning of stationary growth phase when exuded organic materials were obtained.
      Copper-complexing property of the total exuded organic materials and
      exopolysaccharides before and after freeze-drying was evaluated by complexometric
      titrations and Scatchard Plot Analysis of the titration data. The results
      revealed the presence of two copper-complexing ligands in the total exuded
      material, but only one in the exopolysaccharide. Stronger copper-complexing
      ligands are associated to low molecular weight compounds (LogK'1=7.3, LogCL1=
      5.6; LogK'2=6.3, LogCL2=-5.1), whereas weaker ligands to the high molecular
      weight fraction (LogK'2=6.4, LogCL2=-5.6). Although freeze-drying the polymeric
      organic material (exopolysaccharide) may result in conformational changes of the
      molecule, no effect on copper-complexing properties was detected. Gas
      chromatography was used to evaluate the monosaccharide composition of the
      microalgal exopolysaccharide, which detected high content of mannose and 12% of
      acid monosaccharides.

PMID- 15950038
TI  - Fungal degradation of metsulfuron-methyl in pure cultures and soil.
AB  - A fungal strain capable of utilizing metsulfuron-methyl as sole carbon and energy
      sources was isolated from a metsulfuron-methyl treated soil. The degradation
      characteristics of metsulfuron-methyl by this fungal strain were investigated in
      liquid culture and soil. More than 79% of metsulfuron-methyl at concentrations of
      0.10 mgl(-1), 1.0 mgl(-1) and 10.0 mgl(-1) in pure culture was degraded by strain
      MD after incubation for 7 days, whereas only 5.6%, 8.6% and 13.1% of metsulfuron
      methyl were degraded at levels of 0.10 mgl(-1), 1.0mgl(-1) and 10.0 mgl(-1) in
      the controls, respectively. The incorporation of strain MD into soil was found to
      substantially increase the degradation of metsulfuron-methyl. Degradation was 7.5
      and 3.8 times faster in strain MD amended soils than in sterilized and fresh
      soils. The results show that addition of the isolated strain MD enhances
      degradation of metsulfuron-methyl in water and soil.

PMID- 15950039
TI  - Comprehensive characterization of oil refinery effluent-derived humic substances
      using various spectroscopic approaches.
AB  - Refinery effluent-derived humic substances (HS) are important for developing
      refinery effluent reclamation techniques and studying the environmental chemistry
      of wastewater effluents. In this study, dissolved organic matter (DOM) from
      refinery effluent was concentrated using a portable reverse osmosis (RO) system.
      HS were isolated from RO retentates with XAD-8 resin. A variety of approaches
      such as specific UV absorbance at 254nm (SUV(254)), elemental analysis, size
      exclusion chromatography (SEC), solid-state cross polarization magic angle
      spinning (13)C nuclear magnetic resonance spectrometry ((13)C CPMAS NMR), Fourier
      transform infrared spectrometry (FTIR), and electrospray ionization/ion trap/mass
      spectrometry (ESI/ion trap/MS) were employed for characterization of HS. The
      portable RO system exhibited high yield and recovery of DOM for concentrating
      refinery effluent. The concentration of dissolved organic carbon (DOC) in the
      refinery effluent was 9.9mg/l, in which humic acids (HA) and fulvic acids (FA)
      accounted for 2.3% and 34.6%, respectively. Elemental and SUV(254) analyses
      indicated relative high amounts of aliphatic structures and low amounts of
      aromatic structures in refinery effluent-derived HS. Refinery effluent-derived HS
      displayed lower molecular weight than natural HS. The number-average molecular
      weight (M(n)) and the weight-average molecular weight (M(w)) of HA were 1069 and
      2934, and those of FA were 679 and 1212 by SEC, respectively. By ESI/ion trap/MS,
      the M(n) and the M(w) of FA were 330 and 383. Four kinds of carbon structures
      (aliphatic, aromatic, heteroaliphatic, and carboxylic carbons) were found in
      refinery effluent-derived HS by (13)C NMR analysis. The quantitative results
      support the interpretation that these HS are rich in aliphatic carbons and poor
      in aromatic carbons. Proteinaceous materials were identified by FTIR analysis in
      refinery effluent-derived HS.

PMID- 15950040
TI  - Modification of carbon-coated TiO2 by iron to increase adsorptivity and
      photoactivity for phenol.
AB  - Carbon-coated TiO(2) modified by iron, were prepared from TiO(2) of anatase
      structure and PET modified by FeC(2)O(4). Catalysts were prepared by mixing
      powders of TiO(2) and modified PET and heating at different temperatures, from
      400 to 800 degrees C under flow of Ar gas. High adsorption of phenol was observed
      on the catalyst heated at 400 degrees C, confirmed by FT-IR analysis. On this
      catalyst, fast rate of phenol decomposition was achieved by addition of small
      amount of H(2)O(2) to the reaction mixture. Phenol decomposition proceeded mainly
      through the direct oxidation of phenol species adsorbed on the catalyst surface
      due to the photo-Fenton reaction. Iron-modified carbon-coated TiO(2) catalysts
      heated at 500-800 degrees C showed almost no phenol adsorption or oxidation.

PMID- 15950041
TI  - Determination of the organic aerosol mass to organic carbon ratio in IMPROVE
      samples.
AB  - The ratio of organic mass (OM) to organic carbon (OC) in PM(2.5) aerosols at US
      national parks in the IMPROVE network was estimated experimentally from solvent
      extraction of sample filters and from the difference between PM(2.5) mass and
      chemical constituents other than OC (mass balance) in IMPROVE samples from 1988
      to 2003. Archived IMPROVE filters from five IMPROVE sites were extracted with
      dichloromethane (DCM), acetone and water. The extract residues were weighed to
      determine OM and analyzed for OC by thermal optical reflectance (TOR). On
      average, successive extracts of DCM, acetone, and water contained 64%, 21%, and
      15%, respectively, of the extractable OC, respectively. On average, the non-blank
      corrected recovery of the OC initially measured in these samples by TOR was 115+/
      42%. OM/OC ratios from the combined DCM and acetone extracts averaged 1.92 and
      ranged from 1.58 at Indian Gardens, AZ in the Grand Canyon to 2.58 at Mount
      Rainier, WA. The average OM/OC ratio determined by mass balance was 2.07 across
      the IMPROVE network. The sensitivity of this ratio to assumptions concerning
      sulfate neutralization, water uptake by hygroscopic species, soil mass, and
      nitrate volatilization were evaluated. These results suggest that the value of
      1.4 for the OM/OC ratio commonly used for mass and light extinction
      reconstruction in IMPROVE is too low.

PMID- 15950042
TI  - Column studies to investigate the fate of veterinary antibiotics in clay soils
      following slurry application to agricultural land.
AB  - The environment may be exposed to veterinary medicines administered to livestock
      due to the application of organic fertilisers to land. For other groups of
      substances that are applied to agricultural land (e.g. pesticides), preferential
      flow in underdrained clay soils has been identified as an extremely important
      pathway by which pollution of surface waters can occur. Three soil column
      leaching experiments have therefore been carried out using a clay soil to
      investigate the fate of a range of antibiotics from the sulphonamide,
      tetracycline and macrolide groups. These column studies complemented a range of
      other experiments at the field and semi-field scales, as well as modelling
      studies which are being reported in separate papers. Each column study had a
      different objective. The first examined the effect of pig slurry on the mobility
      of antibiotics in clay loam soil. The second experiment investigated changes in
      soil water pH due to the application of slurry. The final experiment quantified
      the extent to which soil tillage prior to slurry application can reduce the
      leaching of antibiotic residues found in slurry. It was found that slurry had no
      impact on the leaching of oxytetracycline although soil water pH was affected
      significantly by slurry application. It was also shown that pre-tillage can
      substantially reduce the leaching of antibiotic residues through macroporous clay
      soils.

PMID- 15950043
TI  - Effects of lead and cadmium nitrate on biomass and substrate utilization pattern
      of soil microbial communities.
AB  - A study was conducted to evaluate the effects of different concentrations of lead
      (Pb) and cadmium (Cd) applied as their nitrates on soil microbial biomass carbon
      (C(mic)) and nitrogen (N(mic)), and substrate utilization pattern of soil
      microbial communities. The C(mic) and N(mic) contents were determined at 0, 14,
      28, 42 and 56 days after heavy metal application (DAA). The results showed a
      significant decline in the C(mic) for all Pb and Cd amended soils from the start
      to 28 DAA. From 28 to 56 DAA, C(mic) contents changed non-significantly for all
      other treatments except for 600 mgkg(-1) Pb and 100 mgkg(-1) Cd in which it
      declined significantly from 42 to 56 DAA. The N(mic) contents also decreased
      significantly from start to 28 DAA for all other Pb and Cd treatments except for
      200 mgkg(-1) Pb which did not show significant difference from the control.
      Control and 200 mgkg(-1) Pb had significantly lower soil microbial biomass C:N
      ratio as compared with other Pb treatments from 14 to 42 DAA, however at 56 DAA,
      only 1000 mgkg(-1) Pb showed significantly higher C:N ratio compared with other
      treatments. No significant difference in C:N ratio for all Cd treated soils was
      seen from start to 28 DAA, however from 42 to 56 DAA, 100 mgkg(-1) Pb showed
      significantly higher C:N ratio compared with other treatments. On 56 DAA,
      substrate utilization pattern of soil microbial communities was determined by
      inoculating Biolog ECO plates. The results indicated that Pb and Cd addition
      inhibited the functional activity of soil microbial communities as indicated by
      the intensity of average well color development (AWCD) during 168 h of
      incubation. Multivariate analysis of sole carbon source utilization pattern
      demonstrated that higher levels of heavy metal application had significantly
      affected soil microbial community structure.

PMID- 15950044
TI  - A PAH fate model for San Francisco Bay.
AB  - A mass balance model was applied to simulate the long-term fate of PAHs in San
      Francisco Bay. The model treats the Bay as a single box with interacting water
      and sediment compartments, and includes loading, volatilization, outflow to the
      ocean, degradation, and burial in deep sediment. The estimated time required for
      loss of one-half of the mass in the Bay in the absence of loading ranged from 20
      d for naphthalene to 5 yr for benzo(b)fluoranthene. Uncertainty analysis using
      Monte Carlo simulation indicated a high degree of influence and uncertainty for
      degradation rates, suggesting that improved estimates of degradation would
      significantly improve the predictive ability of the model. A comparison of model
      calculations to literature values suggested that external PAH loading to San
      Francisco Bay was at or above previous estimates of 3600 kgyr(-1), and that
      degradation in the Bay was within the range of commonly published estimates for
      high molecular weight PAHs (4.0 x 10(-5) to 4.0 x 10(-4)d(-1)).

PMID- 15950045
TI  - The effect of landuse on soil organic carbon chemistry and sorption of pesticides
      and metabolites.
AB  - Earlier studies had shown significant differences in sorption of nine pesticides
      in soils collected from two landuses (native vegetation and market gardens),
      which could not be explained on the basis of organic carbon content alone.
      Consequently it was hypothesised that the differences in sorption behaviour
      between the two landuses may be due to variation in the chemistry of the organic
      carbon. In this study the relationship between sorption behaviour of the nine
      chemicals and soil organic carbon chemistry, as determined by solid-state (13)C
      NMR spectroscopy, was investigated. No significant differences were found between
      the two landuses in the distribution of the four main spectral regions of the
      (13)C NMR spectra of soil OC, except for the carbonyl fraction (165-220ppm),
      which may reflect the low OC content of the soils from both landuses. For all
      chemicals, except prometryne, the most significant (P<0.01 or P<0.001)
      relationship between K(d) values and types of OC was found with the aromatic (110
      165ppm) or the alkyl (0-45ppm) fraction. A comparison was made of the variability
      of K(d) values normalized over OC (i.e. K(oc)), alkyl, aromatic and
      alkyl+aromatic fractions. Expressing K(d) values for all chemicals, except
      azinphos methyl, in soils under native vegetation as K(alkyl) or K(aromatic)
      greatly decreased the variability compared with the K(oc) value. However in the
      cultivated soils only the sorption coefficients for DEA, DIA and fenamiphos
      showed a decrease in variability when expressed as K(alkyl) or K(aromatic). This
      reflected the stronger relationship between sorption coefficients and the alkyl
      and aromatic fraction of soil OC in soils from native vegetation compared with
      those determined from the market garden soils. The different relationships
      between sorption coefficients and types of OC of the two landuses also suggests
      that the type of aromatic and alkyl carbon under the two landuses is different
      and NMR characterisation of the OC was not sufficient to distinguish these
      differences.

PMID- 15950046
TI  - Assessment of heavy metal pollution in surface soils of urban parks in Beijing,
      China.
AB  - Assessing the concentration of potentially harmful heavy metals in the soil of
      urban parks is imperative in order to evaluate the potential risks to residents
      and tourists. To date, little research on soil pollution in China's urban parks
      has been conducted. To identify the concentrations and sources of heavy metals,
      and to assess the soil environmental quality, samples were collected from 30
      urban parks located in the city of Beijing. Subsequently, the concentrations of
      Cu, Ni, Pb and Zn in the samples were analyzed. The investigation revealed that
      the accumulations of Cu and Pb were readily apparent in the soils. The integrated
      pollution index (IPI) of these four metals ranged from 0.97 to 9.21, with the
      highest IPI in the densely populated historic center district (HCD). Using
      multivariate statistic approaches (principal components analysis and hierarchical
      cluster analysis), two factors controlling the heavy metal variability were
      obtained, which accounted for nearly 80% of the total variance. Nickel and Zn
      levels were controlled by parent material in the soils, whereas Cu, Pb and, in
      part, Zn were accounted for mainly by anthropogenic activities. The findings
      presented here indicate that the location and the age of the park are important
      factors in determining the extent of heavy metal, particularly Cu and Pb,
      pollution. In addition, the accumulation of Zn did not appear to reach pollution
      levels, and no obvious pollution by Ni was observed in the soils of the parks in
      Beijing.

PMID- 15950047
TI  - Assessment of heavy metal concentrations in the food web of lake Beysehir,
      Turkey.
AB  - The accumulation of heavy metals (Cd, Pb, Hg and Cr) was measured by atomic
      absorption spectrophotometry in water, sediment, plankton and fish samples
      collected from Lake Beysehir, which is important bird nesting and visiting areas,
      and irrigation and drinking water sources. In Lake Beysehir, the accumulation
      orders of heavy metals were Cd>Pb>Cr>Hg in water, Pb>Cd>Cr>Hg in sediment,
      Pb>Cd>Cr>Hg in plankton, and Cd>Pb>Cr>Hg in the muscles and gills of chub, carp,
      tench, except for the muscle of pikeperch, in which it was Pb>Cd>Cr>Hg (P<0.05).
      In addition to this, accumulation orders of heavy metals in the food web was also
      found to be water>plankton>sediment>fish tissues, except for Cr. According to
      international criterias and Turkish regulations, heavy metal concentrations
      especially Cd and Pb in Lake Beysehir were markedly above the permissible levels
      for drinking water.

PMID- 15950048
TI  - Toxic metal content of particulate matter (PM10), within the Greater Area of
      Athens.
AB  - This study presents results from a yearlong particulate matter measurement
      campaign, conducted across the Greater Athens Area, at four locations, between
      1st June 2001 and 31st May 2002. The collected PM(10) 24-h samples were analyzed
      for nine toxic metals and metalloids (Pb, As, Cd, Ni, Cr, Mn, V, Cu, Hg).
      Concerning the five elements regulated by the European Union, annual average
      concentrations of Pb were found below the limit values at all sites, Cd and Ni
      concentrations were lower than the prospective assessment thresholds at all
      sites, concentrations of As exceeded the assessment threshold at two sites, while
      concentrations of Hg were found below detection limits in all samples.
      Concentration levels of Mn and V were in compliance with the values proposed by
      the World Health Organization. The seasonal and spatial variability of metal
      concentrations was examined and site-specific correlation analysis was conducted
      for the identification of metals with similar origin. The association between
      trace metals and NO(x) concentrations was explored to account for the impact of
      automotive sources, at two traffic-impacted sites. Cu was the metal most closely
      linked with the road transport sector. The relation of concentration levels with
      the prevalence of winds from different sectors was studied in an effort to
      investigate the transport of metal particles from various zones of the city.
      Finally, factor analysis was carried out to extract the main components
      responsible for the variance of the dataset and to attribute them to specific
      source categories, with vehicle-related sources being important in all cases.

PMID- 15950049
TI  - Properties of hydrocarbon- and salt-contaminated flare pit soils in northeastern
      British Columbia (Canada).
AB  - Many contaminated sites in Canada are associated with flare pits generated during
      past petroleum extraction operations. Flare pits are located adjacent to well
      sites, compressor stations and batteries and are often subjected to the disposal
      of wastes from the flaring of gas, liquid hydrocarbons and brine water. This
      study was conducted to evaluate the physical, chemical, electrical and mineral
      properties of three flare pit soils as compared to adjacent control soils.
      Results showed that particle size distribution, pH, total N, cation exchange
      capacity, exchangeable Mg(2+), and sodium adsorption ratio were similar in soils
      from flare pits and control sites. Total C, exchangeable Ca(2+), K(+) and Na(+),
      soluble Ca(2+), Mg(2+), K(+) and Na(+) and electrical conductivity were higher in
      flare pit soils compared to control soils. X-ray diffraction and scanning
      electron microscopic analyses showed the presence of gypsum [CaSO(4).2H(2)O],
      dolomite [CaMg(CO(3))(2)], pyrite [FeS(2)], jarosite [KFe(3)(OH)(6)(SO(4))(2)],
      magnesium sulphate, oxides of copper and iron+copper in salt efflorescence
      observed in flare pit soils. Soils from both flare pits and control sites
      contained mica, kaolonite and 2:1 expanding clays. The salt-rich materials
      altered the ionic equilibria in the flare pit soils; K(Mg-Ca) selectivity
      coefficients in control soils were higher compared to contaminated soils. The
      properties of soils (e.g., high electrical conductivity) affected by inputs
      associated with oil and gas operations might render flare pit soils less
      conducive to the establishment and growth of common agricultural crops and forest
      trees.

PMID- 15950050
TI  - Ozone concentrations at a high altitude station in the Central Massif (Spain).
AB  - In order to contribute to current knowledge of ozone concentrations and transport
      across the Central Massif, a monitoring station was installed at 1780 m on the
      upper Spanish plateau about 55 km from the city of Madrid. Ozone concentrations
      and standard meteorological variables were measured in June and July 2002. A
      smoothed ozone hourly cycle was obtained with mean values of 120 and 110 microgm(
      3) during day-time and night-time, respectively. The highest ozone concentrations
      were recorded in the SE-S-SW wind sectors, proving the influence of transport
      from the Madrid urban plume to the upper plateau. This assumption was also
      supported by the satisfactory correlation between ozone peaks obtained at the
      monitoring site and those recorded in a representative station on the foothill
      located on the lower plateau during episodic situations. To assess the
      contribution of long-range transport, backward air mass trajectories were
      computed each day of measurements at 820 hPa. The lowest ozone mean was linked to
      Atlantic Ocean air masses, and the highest to air masses from Central Europe.

PMID- 15950051
TI  - Relationship between the expression of various markers and prognostic factors in
      breast cancer.
AB  - The immunohistochemical detection of six markers of breast cancer has been
      compared in the present study with known prognostic factors of the disease to
      establish locally a standard panel of markers for the management of breast
      cancer. Sections of tissue of 114 consecutive breast cancer cases were studied
      immunohistochemically, using antibodies against oestrogen receptor (ER),
      progesterone receptor (PR), androgen receptor, c-erbB2, cathepsin D, and cyclin
      D. Marker labelling was graded as recommended in the literature. Using the chi(2)
      test, relationships were determined between marker labelling and histological
      type of cancer, tumour grade, tumour size, axillary lymph node status and age of
      patient. A p value below 0.05 was considered significant. A positive relationship
      was found between ER and PR and lower grades of cancer, and a negative
      relationship was found with medullary and atypical medullary carcinoma. The four
      other markers showed no relationship with grade or type of cancer. All markers
      showed no significant relationship with size of tumour, presence of axillary node
      metastasis or age of patient. There was positive correlation between c-erbB2 and
      cathepsin D. Our study confirms the association between ER and PR and
      histological type and grade of breast cancer, both known parameters of good
      prognosis. We found no consistent relationship between the other four markers and
      prognostic factors studied, other than the suggestion that c-erbB2 and cathepsin
      D may be useful markers for poor prognosis and can be usefully applied locally,
      especially in the light of the current availability of trastuzumab (Herceptin)
      for management of c-erbB2-positive cases. We found no relationship between the
      markers and tumour size, axillary lymph node status or age.

PMID- 15950052
TI  - Changes in distribution patterns of integrins in endometrium in copper T380
      intrauterine device users.
AB  - Intrauterine contraception is the most cost-effective reversible method of
      contraception today, but its mechanism of action is not well understood. Our
      objective was to investigate immunohistochemical distribution patterns of alphav,
      alpha3, beta1 integrins in women using a copper T380 intrauterine device (IUD)
      for different periods of time to obtain insight into the role of integrins in
      intrauterine contraception. Endometrial biopsies were obtained from patients
      using T Cu380A IUD in follicular and luteal phases and in menopausal women
      grouped according to the period of time of IUD use (group 1: <3 year, and group
      2:>or=3 years). Each group consisted of 10 patients, with a total number of 60
      patients. Labelling intensity of all integrins, except for beta1 which increased
      in the follicular phase, were decreased in women who used IUD for>or=3 years when
      compared with group 1 in the follicular and luteal phases and in the menopause.
      We conclude that long-term use of IUD affects integrin expression in endometrium
      not only in follicular and luteal phases of premenopausal women but also in
      postmenopausal women. Copper IUD can inhibit binding of integrins to the
      extracellular matrix and it may cause inhibition of the implantation stage, which
      is crucial for pregnancy.

PMID- 15950053
TI  - Detection of calretinin expression in abnormal immature Sertoli cells in non
      obstructive azoospermia.
AB  - The current study identified for the first time calretinin expression in abnormal
      Sertoli cells of azoospermic men who underwent testicular biopsy for sperm
      recovery and application of the retrieved sperm by in vitro fertilization
      techniques. Testicular biopsies with various spermatogenic impairments were
      evaluated immunohistochemically for the expression of the calretinin calcium
      binding protein and the marker for immaturity of Sertoli cells, cytokeratin-18
      (CK-18). Distribution of the markers was assessed in testes demonstrating a
      histological phenotype of mixed atrophy, Sertoli cell-only, or normal
      spermatogenesis (obstructive-azoospermia) and in men carrying a deletion in the
      azoospermia factor region located on the Y chromosome. Calretinin-immunopositive
      immature Sertoli cells revealed by co-localization of both markers, calretinin
      and CK-18, were identified in the mixed atrophy group in seminiferous tubules
      demonstrating spermatogenic failure. Sertoli cells expressing both markers were
      rarely detected in all other groups. Leydig cells in all the assessed biopsies
      expressed calretinin and served as a built-in control for immunoreactivity. This
      pattern of calretinin-selective expression in immature Sertoli cells suggests a
      functional relationship between calretinin expression and the degree of Sertoli
      cell differentiation. Disorders of Sertoli cell differentiation as indicated by
      calretinin and/or CK-18 expression contribute to the multifactorial mechanisms
      underlying spermatogenic failure.

PMID- 15950054
TI  - A multicolor fluorescence immunostaining technique for simultaneous antigen
      targeting.
AB  - A general problem in immunocytochemistry is the development of a reliable
      multiple immunolabeling method with primary antibodies originating from the same
      host species. Here, we briefly outline different approaches intended to close
      this technological gap and focus on multiple immunolabeling with monoclonal
      primary antibodies. To this end, we generated a basic universal protocol for the
      use of secondary antibodies selectively recognizing different isotypes/subclasses
      of monoclonal primary antibodies. This approach is widely applicable and offers a
      simple procedure for simultaneously detecting two or more antigens.

PMID- 15950055
TI  - Models of the inositol trisphosphate receptor.
AB  - The inositol (1,4,5)-trisphosphate receptor (IPR) plays a crucial role in calcium
      dynamics in a wide range of cell types, and is often a central feature in
      quantitative models of calcium oscillations and waves. We review deterministic
      and stochastic mathematical models of the IPR, from the earliest ones of the
      1970s and 1980s, to the most recent. The effects of IPR stochasticity on Ca2+
      dynamics are briefly discussed.

PMID- 15950056
TI  - Structural and biochemical studies of GH family 12 cellulases: improved thermal
      stability, and ligand complexes.
AB  - In this review we will describe how we have gathered structural and biochemical
      information from several homologous cellulases from one class of glycoside
      hydrolases (GH family 12), and used this information within the framework of a
      protein-engineering program for the design of new variants of these enzymes.
      These variants have been characterized to identify some of the positions and the
      types of mutations in the enzymes that are responsible for some of the
      biochemical differences in thermal stability and activity between the homologous
      enzymes. In this process we have solved the three-dimensional structure of four
      of these homologous GH 12 cellulases: Three fungal enzymes, Humicola grisea
      Cel12A, Hypocrea jecorina Cel12A and Hypocrea schweinitzii Cel12A, and one
      bacterial, Streptomyces sp. 11AG8 Cel12A. We have also determined the three
      dimensional structures of the two most stable H. jecorina Cel12A variants. In
      addition, four ligand-complex structures of the wild-type H. grisea Cel12A enzyme
      have been solved and have made it possible to characterize some of the
      interactions between substrate and enzyme. The structural and biochemical studies
      of these related GH 12 enzymes, and their variants, have provided insight on how
      specific residues contribute to protein thermal stability and enzyme activity.
      This knowledge can serve as a structural toolbox for the design of Cel12A enzymes
      with specific properties and features suited to existing or new applications.

PMID- 15950057
TI  - Sulphate respiration from hydrogen in Desulfovibrio bacteria: a structural
      biology overview.
AB  - Sulphate-reducing organisms are widespread in anaerobic enviroments, including
      the gastrointestinal tract of man and other animals. The study of these bacteria
      has attracted much attention over the years, due also to the fact that they can
      have important implications in industry (in biocorrosion and souring of oil and
      gas deposits), health (in inflamatory bowel diseases) and the environment
      (bioremediation). The characterization of the various components of the electron
      transport chain associated with the hydrogen metabolism in Desulfovibrio has
      generated a large and comprehensive list of studies. This review summarizes the
      more relevant aspects of the current information available on the structural data
      of various molecules associated with hydrogen metabolism, namely hydrogenases and
      cytochromes. The transmembrane redox complexes known to date are also described
      and discussed. Redox-Bohr and cooperativity effects, observed in a few
      cytochromes, and believed to be important for their functional role, are
      discussed. Kinetic studies performed with these redox proteins, showing clues to
      their functional inter-relationship, are also addressed. These provide the
      groundwork for the application of a variety of molecular modelling approaches to
      understanding electron transfer and protein interactions among redox partners,
      leading to the characterization of several transient periplasmic complexes. In
      contrast to the detailed understanding of the periplasmic hydrogen oxidation
      process, very little is known about the cytoplasmic side of the respiratory
      electron transfer chain, in terms of molecular components (with exception of the
      terminal reductases), their structure and the protein-protein interactions
      involved in sulphate reduction. Therefore, a thorough understanding of the
      sulphate respiratory chain in Desulfovibrio remains a challenging task.

PMID- 15950058
TI  - Human placental explants in culture: approaches and assessments.
AB  - Placental explant cultures in vitro are useful for studying tissue functions
      including cellular uptake, production and release of secretory components, cell
      interactions, proliferation, growth and differentiation, gene delivery,
      pharmacology, toxicology, and disease processes. A variety of culture conditions
      are required to mimic in utero environments at different times of gestation
      including differing oxygen partial pressures, extracellular matrices and culture
      medium. Optimization of explant methods is examined for first and third trimester
      human placental tissue and the biological processes under investigation.

PMID- 15950060
TI  - Vascular distribution patterns in monochorionic twin placentas.
AB  - Several recent publications have focused on the association between the
      occurrence of twin-to-twin transfusion syndrome (TTTS) in diamniotic
      monochorionic twins and the presence of a number of selected anatomic placental
      characteristics (distribution of vascular territory, cord insertion, type and
      number of inter-twin anastomoses). In contrast, the potential importance of the
      vascular distribution patterns of the individual twins remains to be elucidated.
      Based on its gross architectural distribution pattern, chorionic vasculature is
      traditionally described as disperse, magistral or mixed. The aim of this study
      was (1) to determine the relative prevalence of these vascular distribution
      patterns in monochorionic twin placentas, and (2) to correlate these patterns
      with the presence of TTTS and known anatomic placental features linked to TTTS.
      The placentas of 89 consecutive diamniotic-monochorionic twins (15 with TTTS, 74
      without TTTS), examined at Women and Infants Hospital, were studied. Disperse
      vascular patterns were seen in 53% of twins, and magistral or mixed patterns in
      47%. The prevalence of magistral/mixed vascular patterns was significantly higher
      in TTTS gestations than in non-TTTS gestations (60% versus 44%, P<0.05) and, in
      TTTS gestations, much higher in donor twins than in recipient twins (87% versus
      33%, P<0.005). A strong association was found between the presence of
      magistral/mixed patterns and marginal/velamentous cord insertion, low number of
      inter-twin anastomoses, and uneven distribution of the vascular territories.
      These findings suggest that the magistral/mixed vascular distribution pattern may
      represent an important placental architectural feature contributing to the
      complex pathophysiology of TTTS.

PMID- 15950059
TI  - Placentation in the African elephant, Loxodonta africanus: III. Ultrastructural
      and functional features of the placenta.
AB  - Successful transfer of nutrients to the elephant fetus during pregnancy relies on
      a variety of placental modifications. Our light and electron microscopical
      investigations show that the structure is endotheliochorial from implantation to
      term, with unicellular, never syncytial trophoblast. Light and electron
      microscope immunocytochemistry shows the restriction of the glucose transporter 1
      isoform to the basolateral surfaces of the trophoblast, with the glucose
      transporter 3 restricted to the apical plasmalemma of the trophoblast. Glucose
      transport to the fetus therefore requires a sequential use of both isoforms.
      Light and electron microscope cytochemistry indicate the presence of iron
      deposits only in the haemophagous zones confirming their iron transport function.
      No trophoblast areas with high concentrations of Calcium binding protein,
      specialised for Calcium transport were found. In situ hybridisation demonstrated
      the presence of IGF-II mRNA in the trophoblast from the earliest stage, with
      TGFbeta1 and HGF-SF mRNA expressed subsequently but only IGF-II and HGF mRNA
      present in the second half of pregnancy. The results are briefly discussed in
      terms of placental growth and function and indicate that the elephant placenta is
      another example of a unique solution to the variety of problems posed by a
      resident fetus.

PMID- 15950061
TI  - Human placental Hofbauer cells express sprouty proteins: a possible modulating
      mechanism of villous branching.
AB  - The development of the chorionic villous tree into a complex and organized
      ramified tubular network can be termed branching morphogenesis. Studying the
      molecular mechanisms involved in this process may contribute to the understanding
      of pregnancy complications such as preeclampsia. Sprouty (Spry) proteins are
      important regulators of branching morphogenesis and growth factor signaling. We
      analyzed the expression of Spry genes in human placenta. RT-PCR and
      immunohistochemistry were employed to detect placental Spry expression.
      Quantitative RT-PCR was used to assess the effect of FGF and reduced oxygen
      fraction on Spry gene expression. Spry 1, 2 and 3 expression was observed in
      placental tissue from all three trimesters. Our results reveal for the first time
      that Spry proteins are localized in the stroma of the chorionic villi, adjacent
      to cytotrophoblasts in areas of villous sprouting. Immunofluorescent double
      staining with anti-Spry and anti-CD68 confirmed that placental macrophages
      (Hofbauer cells) express Spry. Reduced oxygen fraction, FGF-4 and FGF-10
      stimulated Spry-2 expression. Hofbauer cells also expressed c-Cbl, a protein that
      interacts with Spry. Placental expression of Spry and c-Cbl implies an important
      role for Hofbauer cells in placental development, possibly through a mesenchymal
      epithelial interaction with trophoblasts. Regulation of Spry-2 expression by FGF
      4 and FGF-10 suggests an orchestrated regulatory system that modulates villous
      branching.

PMID- 15950062
TI  - Expression of the 5-HT2A serotoninergic receptor in human placenta and
      choriocarcinoma cells: mitogenic implications of serotonin.
AB  - Serotonin (5-hydroxytryptamine, 5-HT) has diverse physiological functions and
      acts as a mitogen in a variety of cell types, including bovine placental cells.
      It exerts its mitogenic effect by interacting with a wide range of 5-HT receptor
      types. Previous studies have reported the presence of 5-HT(2) binding sites in
      human placental trophoblastic cells, but this has never been confirmed at the
      molecular level. In this study, we demonstrated that the 5-HT(2A) receptor
      subtype is fully expressed in the human choriocarcinoma cell lines JEG-3 and BeWo
      as well as in normal human placental tissue. DNA sequencing has confirmed that
      the 5-HT(2A) receptor present in these cell lines and tissues is identical to the
      human 5-HT(2A) receptor found in platelets and in the cerebral cortex. This
      receptor was localized by immunofluorescence on the plasma membrane, in JEG-3 and
      BeWo cells. Furthermore, MTT proliferation assays revealed a positive effect of 5
      HT on the proliferation of JEG-3 and BeWo cells. These results suggest that 5-HT
      constitutes a potent mitogen for neoplastic placental cells.

PMID- 15950064
TI  - Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the
      human placenta and decidua: implications for role of the kynurenine pathway in
      pregnancy.
AB  - Indoleamine 2,3-dioxygenase (IDO) has been implicated in contributing to
      immunotolerance in early pregnancy, but the presence in the term placenta of
      mRNAs for enzymes that produce other biologically active kynurenine end-products
      suggests other functions for kynurenine pathway metabolites. The aim of this
      study was to investigate the localisation of two key enzymes - IDO and kynurenine
      hydroxylase (KYN-OHase) - in first trimester decidua and in the human placenta
      across pregnancy. Using immunocytochemistry, it was shown that there was strong
      expression of IDO and KYN-OHase in stromal and glandular epithelial cells of
      first trimester decidua. In first and second trimester placenta, IDO and KYN
      OHase were localised to the syncytiotrophoblast, stroma and macrophages. IDO and
      KYN-OHase mRNAs were also identified, and the enzymes appear to be functional
      because kynurenine and 3-hydroxy-anthranilic acid (respective products of the
      activity of these enzyme) were released into the medium when first trimester
      placental explants were maintained in culture for 48h. In term placenta, both IDO
      and KYN-OHase immunoreactivities were confined mainly to vascular endothelial
      cells of villous blood vessels, and to macrophages within the fetal villus,
      whereas syncytial staining was very weak or absent. The shift of expression of
      these enzymes away from the syncytiotrophoblast to fetal endothelial cells in
      terminal villi suggests that the function of the enzymes may change from a role
      in immunosuppression at the maternal-fetal interface in early pregnancy, to one
      associated with regulation of fetoplacental blood flow or placental metabolism in
      late gestation.

PMID- 15950063
TI  - Fibrin enhances differentiation, but not apoptosis, and limits hypoxic injury of
      cultured term human trophoblasts.
AB  - We hypothesized that fibrin enhances apoptosis and modulates differentiation of
      trophoblast in vitro. Cytotrophoblasts isolated from normal term human placentas
      were cultured < or =72 h in DMEM-10%-FBS on a fibrin matrix in standard or
      hypoxic conditions. Trophoblasts were cultured on plastic (control), type I
      collagen (matrix control), or dishes with fibrinogen, fibrin degradation products
      (FDP), thrombin, plasma fibronectin or cellular fibronectin. Apoptosis was
      determined by western analysis of the cleavage products of poly-ADP-ribose
      polymerase and cytokeratin 18 and caspase 3 activity. Cell cycle regulation was
      quantified by expression of proliferating cell nuclear antigen (PCNA) and p27
      protein. Differentiation was determined by media level of hCG and hPL. Compared
      to the two controls, fibrin matrix had no effect on trophoblast apoptosis or
      total cell death in standard conditions. Neither fibrin nor collagen altered
      expression of PCNA or p27. In contrast, fibrin significantly increased the
      secretion of both hCG and hPL. Fibrin, but not FDP, thrombin or fibronectins,
      promoted hormonal differentiation. Fibrin limited the impact of a < or =8h of
      hypoxia on trophoblast hormone release but did not avert the effects of 24h of
      low oxygen and did not alter apoptosis in hypoxic trophoblast. We conclude that
      fibrin provides an environment conducive for trophoblast re-epithelialization of
      the surface of villi, where injury is marked by fibrin deposition.

PMID- 15950065
TI  - Less HLA-G expression in Plasmodium falciparum-infected third trimester placentas
      is associated with more natural killer cells.
AB  - During pregnancy, maternal immune tolerance of the fetal semi-allogeneic graft is
      partly the consequence of extravillous trophoblast HLA-G expression and its
      interaction with natural killer (NK) cells. Plasmodium falciparum malaria is
      frequently associated with maternal and fetal complications. Local HLA-G
      expression and the number of NK cells were evaluated immunohistochemically in P.
      falciparum-infected and uninfected placentas (15 each) collected in a seasonal
      malaria-hypoendemic area. In control placentas, HLA-G was almost always expressed
      in extravillous trophoblast whereas, in infected placentas, it was significantly
      more weakly expressed in extravillous trophoblast but was also detected in
      intervillous space macrophages. NK cells were evaluated in intervillous and
      intravillous spaces and in basal plate. NK cells were always more abundant in
      basal plate than in intervillous and intravillous spaces in infected or control
      placentas. For each area, more NK cells were seen in infected than control
      placentas. These data suggest that HLA-G down-regulation and more NK cells in
      placentas may be among the mechanisms involved in poor birth outcome associated
      with P. falciparum infection.

PMID- 15950066
TI  - Prenatal organochlorine pesticides in placentas from Finland: exposure of male
      infants born during 1997-2001.

PMID- 15950067
TI  - The dawn of a new era of biomedical publication.

PMID- 15950068
TI  - Effects of HRAS oncogene on cell cycle progression in a cervical cancer-derived
      cell line.
AB  - BACKGROUND: Human papillomavirus (HPV) infection is the most prevalent factor in
      anogenital cancers. However, epidemiological surveys and molecular data indicate
      that viral presence is not enough to induce cervical cancer, suggesting that
      cellular factors could play a key role. One of the most important genes involved
      in cancer development is the RAS oncogene, and activating mutations in this gene
      have been associated with HPV infection and cervical neoplasia. Thus, we
      determined the effect of HRAS oncogene expression on cell proliferation in a cell
      line immortalized by E6 and E7 oncogenes. METHODS: HPV positive human cervical
      carcinoma-derived cell lines (HeLa), previously transfected with the HRAS
      oncogene or the empty vector, were used. We first determined the proliferation
      rate and cell cycle profile of these cells by using flow cytometry and BrdU
      incorporation assays. In order to determine the signaling pathway regulated by
      HRAS and implicated in the alteration of proliferation of these cells, we used
      specific chemical inhibitors to inactivate the Raf and PI3K pathways. RESULTS: We
      observed that HeLa cells stably transfected with oncogenic HRAS progressed faster
      than control cells on the cell cycle by reducing their G1 phase. Additionally,
      HRAS overexpression accelerated the G1/S transition. Specific chemical inhibitors
      for PI3K and MEK activities indicated that both PI3K/AKT and RAF/MEK/ERK pathways
      are involved in the HRAS oncogene-induced reduction of the G1 phase. CONCLUSIONS:
      Our results suggest that the HRAS oncogene could play an important role in the
      development of cervical cancer, in addition to the presence of HPV, by reducing
      the G1 phase and accelerating the G1/S transition of infected cells.

PMID- 15950069
TI  - Model of the TBP-TFIIB complex from Plasmodium falciparum: interface analysis and
      perspectives as a new target for antimalarial design.
AB  - BACKGROUND: Malaria affects 200-300 million individuals per year worldwide.
      Plasmodium falciparum is the causative agent of the most severe and mortal type
      of malaria. The need for new antimalarials comes from the widespread resistance
      to those in current use. New antimalarial targets are required to increase
      chemical diversity and effectiveness of the drugs. The research for such new
      targets and drug chemotypes is aided by structure-based drug design. We present a
      model of the TBP-TFIIB complex from P. falciparum (pfTBP-pfTFIIB) and a detailed
      study of the interactions at the TBP-TFIIB interface. METHODS: The model was
      built using standard methodology, optimized energetically and evaluated
      structurally. We carried out an analysis of the interface considering its
      evolution, available experimental data on TBP and TFIIB mutants, and the main
      conserved and non-conserved interactions. To support the perspective of using
      this complex as a new target for rational antimalarial design, we present the
      comparison of the pfTBP-pfTFIIB interface with its human homolog. RESULTS:
      Despite the high residue conservation at the interface, we identified a potential
      region, composed of species-specific residues that can be used for rational
      antimalarial design. CONCLUSIONS: Currently there are no antimalarial drugs
      targeted to stop the nuclear transcription process, a vital event for all
      replication stages of P. falciparum. Due to its absolute requirement in
      transcription initiation, we consider the pfTBP-pfTFIIB interface as a new
      potential target for novel antimalarial chemotypes.

PMID- 15950070
TI  - A rat endometrial cell line (R1-49E1) expressing estrogen receptor-alpha
      regulated by the tet-off system.
AB  - BACKGROUND: Estrogens exert profound effects on target tissues. These effects are
      mediated by two estrogen receptors (ER(alpha) and ER(beta)) that bind to specific
      DNA sequences in estrogen-dependent genes. Other molecules such as growth
      factors, transcription factors and some oncoproteins might interact with the
      estrogen receptors and thus regulate the transcription of these genes. Currently
      there is no adequate cellular model to study these interactions. METHODS: We
      transfected the human wild-type ER(alpha) to an ER-negative rat epithelial
      endometrial cell line (Rentr01) using a tetracycline-regulated gene expression
      system. The exogenous receptor was correctly translated, had an appropriate
      hormone-binding affinity, and bound well to estrogen response elements containing
      DNA. RESULTS: We obtained a new stable cell line that is ER(beta) negative but
      ER(alpha) positive (R1-49E1). The expression of receptor alpha can be regulated
      in a dose-response manner by addition of tetracycline in the culture medium.
      Estradiol treatment of ER(alpha)-containing cells apparently diminished cellular
      proliferation, and the exogenous receptor can induce the transcription of the
      endogenous progesterone receptor isoform B (PgR-B) gene. CONCLUSIONS: This
      epithelial cellular model may be useful to study the interaction between
      estrogens and other cell signaling pathways in epithelial endometrial cell
      physiology.

PMID- 15950071
TI  - Early and late effects of X-irradiation on submandibular gland: a morphological
      study in mice.
AB  - BACKGROUND: Radiotherapy for head and neck cancers causes permanent salivary
      gland dysfunction and xerostomia. The aim of this study was to determine changes
      in mice submandibular glands after X-irradiation. METHODS: The submandibular
      glands of male C57BL/6 mice were locally X-irradiated in the head and neck region
      with a single dose of 7.5 or 15 Gy and analyzed morphologically and
      morphometrically at 1, 3, 6, 10, 40, and 90 days after irradiation. RESULTS: Two
      phases of gland reaction to irradiation have been noted. The first, early phase
      is observed up to 10 days after irradiation. The second, late phase was observed
      90 days after irradiation. Also, a dose-related effect was noticed. The most
      prominent morphological changes were pyknotic nuclei, vacuolization of acinar
      cells and lysis of acini and granular convoluted tubules. Changes were detected
      at 3 and 6 days after irradiation followed by tissue regeneration. Ninety days
      after irradiation, prominent pathological changes (vacuolization and pyknotic
      nuclei of acinar cells, lysis of acini and granular convoluted tubules and edema)
      were detected, but the most remarkable change was disseminated mononuclear
      infiltration. Also, a statistically significant reduction in number of acinar
      cells was detected in both irradiated glands. CONCLUSIONS: Occurrence of
      disseminated mononuclear infiltration in gland during late post-irradiation phase
      makes the mouse model potentially better than the rat model for investigation of
      irradiation-induced salivary gland damage.

PMID- 15950072
TI  - Evaluation of the BIOCEN GC agar medium base in antimicrobial susceptibility
      testing of Neisseria gonorrhoeae.
AB  - BACKGROUND: Since 1995, the Cuban Reference Laboratory for Neisseria has been
      monitoring the antibiotic susceptibility of gonococci, following the methodology
      of the National Committee for Clinical Laboratory Standards, which uses GC agar
      medium base supplemented with 1% Vitox. We evaluated three lots of GC agar medium
      base produced by BIOCEN, Cuba, in antibiotic susceptibility testing of reference
      and wild strains of gonococci. METHODS: The susceptibilities to five antibiotics
      were evaluated five times on three lots of GC agar medium base from BIOCEN. Four
      and one gonococcal reference strains were tested by MIC dilution and disc
      diffusion methods, respectively. Later, the antimicrobial susceptibilities of ten
      wild Neisseria gonorrhoeae strains were tested in triplicate. As internal
      control, a GC agar medium from Difco was used. RESULTS: All antibiotic MICs
      obtained on four lots of GC agar medium from different manufacturers fell within
      the proposed quality control limits for reference strains analyzed. The disc
      diffusion data for the reference strain of N. gonorrhoeae ATCC 49226 to five
      antibiotics provided essentially identical results in all lots of GC agar medium
      base. For wild strains of gonococci, identical modal MIC values and zone size
      diameters within a 3-mm range were observed in all the antibiotics tested.
      CONCLUSIONS: Excellent agreement in susceptibility testing methods among
      different lots of GC agar medium base from BIOCEN and Difco was obtained for all
      reference and wild gonococcal strains and antibiotics tested. We proposed that GC
      medium from BIOCEN can be used in antimicrobial susceptibility testing of N.
      gonorrhoeae by MIC dilution and disc diffusion tests.

PMID- 15950073
TI  - Oxidative damage in the kidney induced by 900-MHz-emitted mobile phone:
      protection by melatonin.
AB  - BACKGROUND: The mobile phones emitting 900-MHz electromagnetic radiation (EMR)
      may be mainly absorbed by kidneys because they are often carried in belts.
      Melatonin, the chief secretory product of the pineal gland, was recently found to
      be a potent free radical scavenger and antioxidant. The aim of this study was to
      examine 900-MHz mobile phone-induced oxidative stress that promotes production of
      reactive oxygen species (ROS) on renal tubular damage and the role of melatonin
      on kidney tissue against possible oxidative damage in rats. METHODS: The animals
      were randomly grouped as follows: 1) sham-operated control group and 2) study
      groups: i) 900-MHz EMR exposed (30 min/day for 10 days) group and ii) 900-MHz EMR
      exposed+melatonin (100 microg kg(-1) s.c. before the daily EMR exposure) treated
      group. Malondialdehyde (MDA), an index of lipid peroxidation), and urine N-acetyl
      beta-d-glucosaminidase (NAG), a marker of renal tubular damage were used as
      markers of oxidative stress-induced renal impairment. Superoxide dismutase (SOD),
      catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to
      evaluate the changes of antioxidant status. RESULTS: In the EMR-exposed group,
      while tissue MDA and urine NAG levels increased, SOD, CAT, and GSH-Px activities
      were reduced. Melatonin treatment reversed these effects as well. In this study,
      the increase in MDA levels of renal tissue and in urine NAG and also the decrease
      in renal SOD, CAT, GSH-Px activities demonstrated the role of oxidative mechanism
      induced by 900-MHz mobile phone exposure, and melatonin, via its free radical
      scavenging and antioxidant properties, ameliorated oxidative tissue injury in rat
      kidney. CONCLUSIONS: These results show that melatonin may exhibit a protective
      effect on mobile phone-induced renal impairment in rats.

PMID- 15950074
TI  - Biochemical identification and molecular characterization (PCR-RFLP) of Nocardia
      isolates from sputum.
AB  - BACKGROUND: Nocardia identification has been based on biochemical and
      morphological characteristics. However, molecular biology techniques allow a
      better characterization of species and biotypes that are related to invasive
      diseases. METHODS: Twelve isolates of Nocardia spp. were obtained from sputum of
      patients with tuberculosis under retreatment. Identification was done based on
      morphological characteristics, biochemical tests (casein, tyrosine, xanthine,
      gelatin, and urea) and molecular biology techniques (PCR-RFLP) using restriction
      enzymes MspI, HinfI, BsaHI, HaeIII and BstEII. RESULTS: Biochemical tests
      identified the 12 isolates as Nocardia asteroides. PCR-RFLP technique identified
      nine isolates to species and biotype level: five as N. asteroides type II, two as
      N. asteroides type VI, and two as N. asteroides type I. The remaining three
      isolates were identified as follows: one to species level as N. farcinica and two
      at genus level as Nocardia sp. CONCLUSIONS: Significant statistical differences
      between the use of traditional techniques and PCR-RFLP were not found at genus
      level, but there were important differences at species and biotype level.
      Biochemical tests identified correctly the actinomycete isolates as belonging to
      Nocardia genus, but at N. asteroides complex level were not able to discern among
      their different species. PCR-RFLP is a rapid, non-expensive, and reliable method
      that allows to discriminate the N. asteroides complex species, identifying
      biotypes related to invasive disease. Our results suggest that the hospital
      environment was not a contamination source.

PMID- 15950075
TI  - Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese
      subjects.
AB  - BACKGROUND: Epidemiological evidence shows a strong relationship between
      decreased serum magnesium levels (DSML) and insulin resistance. As nonalcoholic
      steatohepatitis (NASH) seems to be related to insulin resistance, the aim of this
      study was to determine the potential relationship between DSML and NASH in obese
      subjects. METHODS: We compared obese individuals with the diagnosis of diabetes,
      insulin-resistance, and non-insulin resistance to a control group of non-obese,
      non-insulin-resistant subjects. Participants were required to have negative viral
      markers and negligible alcohol intake. Other liver diseases and well-known causes
      for decreasing of magnesium were exclusion criteria. A liver biopsy was performed
      in subjects with aspartate aminotransferase (AST) and alanine aminotransferease
      (ALT) levels > or =40 IU/mL. RESULTS: Of the 60 obese subjects, 20 were non
      insulin resistant, 20 were insulin resistant, and 20 were type 2 diabetics.
      Twenty subjects were in the control group. Eleven (33.3%) diabetics, 14 (42.4%)
      insulin-resistant subjects, and 8 (24.2%) non-insulin-resistant subjects
      underwent liver biopsies. Diagnosis of NASH was established in 29 (36.2%)
      individuals. Subjects with the diagnosis of NASH exhibited lower serum magnesium
      levels of 1.7 +/- 0.2 mg/dL (0.70 +/- 0.08 mmol/L), and those with fibrosis
      showed the lowest serum magnesium concentration at 1.5 +/- 0.3 mg/dL (0.62 +/-
      0.12 mmol/L). Multiple regression analysis adjusted by age showed that low serum
      magnesium concentration was independently related to a high HOMA-IR index (OR
      7.6, CI 95% 2.1-11.2; p <0.0001) and that a high HOMA-IR index was related to
      NASH (OR 6.5, CI 95% 1.5-8.8; p <0.01). After adjusting for age and a high HOMA
      IR index, hypomagnesemia remained independently related to NASH (OR 1.4, CI 95%
      1.1-5.4; p <0.05). CONCLUSIONS: The results of this study demonstrate an
      independent relationship between DSML and NASH.

PMID- 15950076
TI  - Cardiac troponin T (cTnT) in hemodialysis patients with asymptomatic and
      symptomatic atherosclerosis.
AB  - BACKGROUND: Cardiovascular mortality is higher in hemodialysis (HD) patients than
      in the general population. Cardiac troponin T (cTnT) is established as a
      sensitive marker of myocardial injury in the general population. Less is known
      about the association between cTnT and intima-media thickness (IMT) and presence
      of plaques in carotid arteries (asymptomatic atherosclerosis) and prognostic
      value of cTnT for cardiovascular mortality (symptomatic atherosclerosis) in HD
      patients. METHODS: In our study 90 HD patients (mean age 56.2 +/- 13.3 years)
      were followed after determination of cTnT level. Outcome after 21 months was
      chosen as the end point. In 52 randomly selected HD patients, IMT was measured
      with B-mode ultrasonography. Plaque occurrence and their numbers were also
      determined. RESULTS: In 24 (26.6%) patients, cTnT values were >0.1 microg/L
      (positive test for myocardial injury). During follow-up, 13 patients died from
      cardiovascular causes and their cTnT values were significantly higher (0.12 vs.
      0.06 microg/L; p <0.001) than in those who survived. Correlation between
      cardiovascular mortality and cTnT was found (p <0.001). The cut-off level of 0.1
      microg/L resulted in survival rates of 92% and 64% (p=0.0006). The IMT values of
      carotid artery were significantly higher (0.85 vs. 0.70 mm; p <0.011) in patients
      with elevated cTnT. All patients with elevated cTnT had plaques and the number of
      plaques was significantly higher in these patients (p <0.0001). CONCLUSIONS: cTnT
      was frequently elevated in our HD patients and was associated with higher
      cardiovascular mortality and a predictor of cardiovascular outcome. Patients with
      elevated cTnT showed advanced asymptomatic atherosclerosis in carotid arteries.

PMID- 15950077
TI  - The antiphospholipid antibody syndrome research in patients with retinal venous
      occlusion.
AB  - BACKGROUND: The antiphospholipid antibody syndrome (APAS) is a condition
      associated with abnormal thrombosis and the presence of anticardiolipin
      antibodies (aCL). METHODS: Thirty-two patients (20 male and 12 female) aged
      between 29 and 75 years (mean +/- SD: 56.4 +/- 12.34) with retinal venous
      occlusive disease were studied. All patients with a history of venous occlusive
      disease within the previous 8 months were included in the study. Diagnoses were
      made by fundus examination and fundus fluorescein angiography (FFA).
      Anticardiolipin IgM and IgG antibodies, antinuclear antibodies (ANA), and IL
      1beta were investigated in all patients. RESULTS: Neither aCL-IgM nor aCL-IgG was
      observed as positive in this group. Only four patients were found to be ANA
      positive. However, serum levels of IL-1beta were higher than those of controls (p
      <0.001). Mean IL-1beta was found to be 18.06 +/- 3.39 pg/mL (mean +/- SE),
      respectively. IL-1beta levels were found to be significantly different from those
      of controls (2.7 +/- 0.68 pg/mL) (p <0.001). In this study, antiphospholipid
      antibody positivity was not determined in any patients. CONCLUSIONS: As a result,
      IL-1beta level appears higher in retinal venous occlusive disease. This cytokine
      measurement might be used as a diagnostic indicator for venous occlusive disease.

PMID- 15950078
TI  - Total antioxidant capacity and levels of epidermal growth factor and nitric oxide
      in blood and saliva of insulin-dependent diabetic patients.
AB  - BACKGROUND: The aim of this study was to examine how type 1 diabetic patients
      have altered levels of lipid peroxidation, antioxidant defense, NO and EGF in
      their plasma and saliva. We tested the differences in lipid peroxidation level,
      antioxidant power, and concentrations of epidermal growth factor (EGF) and nitric
      oxide (NO) in saliva and blood of type 1 diabetic subjects in comparison to
      healthy control subjects. METHODS: Nineteen subjects with type 1 diabetes
      mellitus and 19 healthy age- and sex-matched control subjects were included in
      the study. Blood and saliva samples were obtained and analyzed for thiobarbituric
      reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing
      ability (total antioxidant power), EGF and NO levels. RESULTS: TBARS levels did
      not show a significant difference between the two groups. Analysis of antioxidant
      power revealed that saliva and plasma of diabetic patients had more antioxidant
      power (p <0.01) than the healthy control population (107 +/- 10.35 vs. 11.14 +/-
      4.66 and 192 +/- 12.3 vs. 142 +/- 15.2 mmol/L, respectively). Concentration of
      EGF was increased (p <0.01) in saliva whereas it was reduced (p <0.01) in plasma
      of diabetic patients in comparison to those of healthy subjects (2423 +/- 322 vs.
      1513 +/- 341 and 125 +/- 14 vs. 346 +/- 60 pg/mL, respectively). NO level
      increased in both saliva and plasma of diabetic patients in comparison to those
      of healthy subjects (46.61 +/- 7 vs. 72.89 +/- 13 and 62.11 +/- 4.6 vs. 76.25 +/-
      5 micromol/L, respectively). Blood HbA1c (%) of patients was significantly higher
      than that of controls (8.3 +/- 0.32 vs. 5.4 +/- 0.24, p <0.01). CONCLUSIONS:
      Existence of increased total antioxidant power in the presence of normal lipid
      peroxidation in plasma and saliva of type 1 diabetic patients indicates the
      existence of oxidative stress. Increased salivary EGF and NO levels in
      association with elevated TAOP is interesting and should be further studied.

PMID- 15950079
TI  - High correlation of human immunodeficiency virus type-1 viral load measured in
      dried-blood spot samples and in plasma under different storage conditions.
AB  - BACKGROUND: To measure HIV-1 RNA concentration requires venous extraction of
      blood, use of RNAase-free materials, and transport in a cold chain, which makes
      difficult the management of samples in developing countries. We evaluated the
      utility of the determination of HIV-1 RNA concentration in blood samples dried on
      filter paper (DBS) and subjected to different conditions, as contrasted with
      determination in plasma. METHODS: HIV-1 RNA concentration was determined in HIV
      infected patients in DBS and in plasma samples. Samples were subjected to the
      following: DBS were stored at 4, 22, and 37 degrees C for 1, 3, and 7 days;
      samples from patients from four regions of Mexico were mailed to a reference
      laboratory; DBS were sent under environmental conditions; and plasma samples were
      sent frozen. HIV-1 RNA concentrations were determined by NucliSens in DBS and by
      Amplicor test in plasma. RESULTS: HIV-1 RNA concentration determined in DBS
      subjected to different temperatures and times had a significant correlation
      (r=0.99) with those obtained in plasma. When compared with values in plasma,
      Kappa agreement coefficients of values in DBS stored for 7 days at 4, 22, and 37
      degrees C were 0.98, 0.83, and 0.94, respectively. Quantification of HIV-1 RNA in
      108 DBS mailed from remote areas with different climates demonstrated significant
      correlation with those obtained in plasma (r=0.95; p <0.001). CONCLUSIONS: DBS is
      a simple and reliable method to measure HIV-1 RNA concentration, especially when
      samples are mailed from remote areas to a reference center. This collection
      method is an economic and suitable alternative for use in developing countries.

PMID- 15950080
TI  - Lipid profile and anticardiolipin antibodies in Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystem disorder characterized by a
      relapsing inflammatory process of unknown etiology. It is well known that
      atherothrombosis in systemic inflammatory disorders is closely related to
      coagulation and lipid metabolism abnormalities. The purpose of this study was to
      investigate some parameters of lipid metabolism, lipoprotein (a) [Lp(a)] and
      anticardiolipin antibody (ACA) levels and the relationship of these parameters
      with the clinical activity of BD. METHODS: Thirty three patients with BD (15
      active, 18 inactive cases) and 20 healthy controls participated in the study.
      After performing a detailed physical exam, erythrocyte sedimentation rate (ESR),
      C-reactive protein (CRP), total cholesterol (TC), triglycerides (TG), high
      density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL
      C), very-low-density lipoprotein cholesterol (VLDL-C), apoprotein A and B (apo-A,
      apo-B), Lp(a), and ACA levels (ACA-IgG and IgM) were measured in all
      participants. RESULTS: Patients with active BD had higher ESR, CRP and Lp(a)
      levels, and lower apo-A and HDL-C levels compared with the patients with inactive
      BD and healthy controls. ACA-IgG and IgM levels were higher in patients with
      active BD than healthy controls but not higher than patients with inactive BD. On
      the other hand, ACA-IgG level was higher in active and inactive cases with
      vascular involvement than in those of active and inactive cases without vascular
      involvement. In the analyses of correlation, in active BD patients we found a
      positive correlation between CRP and Lp(a) levels. CONCLUSIONS: Our findings
      suggest that Lp(a) behaves as an acute phase reactant and ACA levels are
      increased in patients with active BD. Data from patients with active BD may be
      compatible with the serum profile, which is accepted as a risk for the
      development of atherothrombosis.

PMID- 15950081
TI  - Evaluation of depressive symptoms and sleep alterations in college students.
AB  - BACKGROUND: Increasing evidence suggests that sleep alterations could favor
      subsequent depression development. In order to identify the simultaneous
      occurrence of these parameters in young people, in this work we evaluated the
      prevalence of depressive symptoms, sleep habits, and possible sleep disturbances
      in college students. METHODS: Beck Depression Inventory (BDI), Epworth Sleepiness
      Scale (ESS), and a Sleep Habits Questionnaire were applied to students registered
      at the Autonomous University of Yucatan, Merida (mean age 20.2 +/- 2.6 years).
      The final sample was composed of 340 (53%) women and 298 (47%) men. Reliability
      of the BDI and ESS was assessed by Cronbach's alpha method. RESULTS: Taking 10 as
      ESS cut-off point, it was found that 31.6% of the students had a high level of
      sleepiness. Students with depressive symptoms had a greater number of days with
      somnolence during class (p <0.05) and perceived that this affected their academic
      performance at a higher level (p <0.001) than the students without symptoms. In
      comparison to subjects without depressive symptoms, students with those symptoms
      rated their sleep quality as poor (p <0.001), perceived a greater latency to
      initiate sleep after going to bed (p <0.03), and experienced a greater number of
      awakenings (p <0.04). CONCLUSIONS: We found diverse sleep alterations in a large
      proportion of the studied subjects, which were more severe in those who showed
      depressive symptoms. Educating students for appropriate sleep hygiene and
      encouraging them to seek professional advice to treat sleep disturbances may be
      useful to prevent depression.

PMID- 15950082
TI  - Epidemic strain Shigella dysenteriae Type 1 Dt66 encodes several drug resistances
      by chromosome.
AB  - BACKGROUND: Multiple antibiotic-resistant strains of Shigella dysenteriae type 1
      were isolated from an epidemic in West Bengal, India (1984). During the past two
      decades, much attention was given to reevaluation of treatment recommendations.
      However, there are no useful data on drug resistance encoded by chromosome.
      METHODS: A total of 300 strains of Shigella dysenteriae type 1 were isolated from
      an epidemic. Strains were biochemically identified by API 20E system and further
      confirmed serologically. Antibiotic susceptibility was determined by disk
      diffusion method and plasmid DNA was prepared by alkaline lysis procedure.
      Elimination of plasmids was achieved by curing with acridine orange from a
      representative epidemic strain S. dysenteriae 1 Dt66. PFGE was performed for
      typing of wild-type and plasmid-cured strains. Southern blot of PFGE separated
      XbaI digested chromosomal DNA was done onto positively charged nylon membrane.
      For Southern hybridization, plasmid DNA was used as probe. RESULTS: All isolates
      showed identical drug resistance patterns and plasmid profiles. All these
      isolates contained six plasmids ranging in sizes from 3 to 145 kb. We have
      eliminated all the plasmids from a representative strain of S. dysenteriae 1 Dt66
      by using acridine orange as curing agent. All epidemic Shigella isolates were
      resistant to amoxycillin, ampicillin, bacitracin, carbenicillin, cefixime,
      ceftazidime, chloramphenicol, clarithromycin, erythromycin, fusidic acid,
      methicillin, penicillin G, polymixin B, streptomycin, rifampicin, tetracycline
      and vancomycin, among 29 antibiotics used. Out of 17 resistant antibiotics, 12
      were encoded by chromosome. Resistance to ampicillin, chloramphenicol,
      streptomycin, tetracycline and ceftazidime was plasmid encoded. Southern blot
      hybridization showed the recognition of two clear sites in the chromosome used
      plasmid DNA of Dt66 strain as probe, which reveled some sequential genetic
      homology between chromosome and plasmids. Pulsed-field gel electrophoresis (PFGE)
      was performed for typing of the chromosome of plasmidless strains of Dt66 and
      wild-type strain Dt66 (having plasmids) that remain unaltered. CONCLUSIONS:
      Seventy percent drug-resistant loci of Shigella dysenteriae 1 Dt66 are present in
      chromosome and the remaining are plasmid mediated.

PMID- 15950083
TI  - Hypertension, overweight and abdominal adiposity in women. An analytical
      perspective.
AB  - BACKGROUND: The aim of our study was to determine in a group of premenopausal
      (preM) and postmenopausal women with hormone replacement therapy (postM-HRT) or
      without HRT (postM-noHRT) whether the strength of the association of body mass
      index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with
      hypertension is affected by the way in which these variables are used (i.e.,
      continuous or dichotomous) in logistic regression modeling, where weight and age
      are set as continuous variables only. METHODS: We studied 639 preM, 341 postM
      noHRT, and 77 postM-HRT healthy women age 20-69 years. The main outcome variable
      was hypertension: BP > or =140 or 90 mmHg on two occasions or hypertension
      treatment. Risk factors were assessed as continuous variables (age,
      postmenopausal years, weight, stature, BMI, WC, hip circumference, and WHR); and
      dichotomous variables (overweight: BMI > or =25; high WC: WC > or =88 cm; and
      high WHR: WHR > or =0.84). Stepwise regression models for hypertension were
      developed for continuous (model 1) and dichotomous (model 2) variables in each
      group. RESULTS: In preM, model 1 included BMI (OR=1.202, CI: 1.115-1.296) and age
      (OR=1.154, CI: 1.081-1.296); and model 2 included weight (OR=1.070, CI: 1.040
      1.100) and age (OR=1.157, CI: 1.084-1.235). In postM-noHRT, both models included
      age (OR=1.074, CI: 1.035-1.113) and weight (OR=1.025, CI: 1.004-1.046).
      Overweight and age were associated with hypertension in preM and postM-noHRT;
      overweight being more relevant in preM, and age in postM-noHRT. No models were
      found for postM-HRT. CONCLUSIONS: The strength of the association of risk factors
      with hypertension depends on how the variables are analyzed. Acknowledging these
      differential effects and assigning differential risks by age could be useful in
      intervention programs.

PMID- 15950084
TI  - Genetic diversity at the FMR1 locus in Mexican population.
AB  - BACKGROUND: Fragile X syndrome is the most frequent cause of inherited mental
      retardation; it is caused by expansion of CGG repeats in the first exon of the
      FMR1 gene. Number of CGG repeats varies between 6 and 50 triplets in normal
      individuals and the most common alleles have 29 or 30 repeats. Allelic patterns
      in the global population are similar; however, some reports show statistical
      differences among several populations. Distribution of allelic frequencies for
      FMR1 locus has not been reported in Mexican population. METHODS: Determination of
      the CGG repeat number was achieved by polymerase chain reaction (PCR) on modified
      DNA from 129 unrelated Mexican mestizos (46 FRAXA-negative males with mental
      retardation and 83 healthy individuals). DNA modification by sodium bisulfite
      achieves conversion of unmethylated cytosine residues to uracil, which allows
      efficient amplification by single PCR. Methylation status of FMR1 region for each
      individual was also established. DNA sequencing of a number of amplified samples
      was realized to validate the procedure. RESULTS: Molecular analysis of the FMR1
      gene showed 23 different alleles. Statistical comparison of allelic length
      between healthy and affected individuals does not show significant differences.
      Trinucleotide repeat number varied from 16-40, with modal number of 32 (27.58%),
      second peak at 30 (25.28%), and minor peak at 34 (10.34%). Together, allelic
      distribution in the Mexican sample differs significantly from those reported for
      Caucasian, Chinese, African, Indonesian, Brazilian, Chilean, and Mixtec
      populations. An excess of large alleles (> or =34 repeats) was evident.
      CONCLUSIONS: Allele distribution in FMR1 gene from Mexican mestizos is different
      from that of other reported populations around the world. This unusual modal
      pattern probably is related to the particular ethnic background of the Mexican
      population. On the other hand, PCR on modified DNA is a valuable and efficient
      method for determination of CGG repetitive sequences in FMR1 gene.

PMID- 15950085
TI  - Renal arteriographic data of young male patients with suspected renovascular
      hypertension.
AB  - The aim of the study was to determine whether the anatomical variant in which one
      or more renal vessels arose from the aorta was associated with hypertension in
      young male patients. We investigated the renal arteriographic data of 73 young
      male patients (age: 27.4 +/- 7.4, blood pressure: 162.7 +/- 17.5/104.6 +/- 10.1
      mmHg) with grade-II hypertension. All studied patients underwent angiography to
      exclude renal artery stenosis. The patients were divided into two groups on the
      basis of their renal angiograms. We determined no abnormal findings in 33 renal
      arteriograms (45.2%). Twenty three (31.5%) patients had an additional renal
      artery without renal artery stenosis or renal anatomical variations. In
      conclusion, although the significance of this form of hypertension is still
      largely obscure, we believe that the presence of additional renal arteries may be
      associated with hypertension.

PMID- 15950086
TI  - Moyamoya syndrome in a child with Down syndrome.
AB  - Moyamoya syndrome has rarely been reported in association with Down syndrome. We
      report a case of an 11-year-old female child with Down syndrome who presented
      with hemiparesis and facial palsy. Imaging investigations (magnetic resonance
      angiography and digital subtraction angiography) revealed the classical Moyamoya
      pattern. Work-up for prothrombotic and autoimmune disorders was negative. The
      neurological deficits recovered well. The association of Moyamoya syndrome in
      patients with Down syndrome has been highlighted. The possible causes for the
      association and management have been reviewed briefly.

PMID- 15950087
TI  - The social production of health: critical contributions from evolutionary,
      biological, and cultural anthropology.
AB  - In 1946, the newly formed World Health Organization boldly sought to
      conceptualize "health" as wellbeing in the positive sense, "not merely the
      absence of disease or infirmity." Yet nearly six decades later, researchers are
      still principally concerned with pathology and its characteristics and
      consequences. This special issue is the result of an effort to broaden the focus.
      Anthropologists working from evolutionary, biological and sociocultural
      perspectives and in diverse geographic regions were asked to examine meanings
      associated with health and/or to identify social conditions and practices that
      have contributed to positive physiological and psychological states in particular
      cultures, times, or across time. Most notable, perhaps, was discovering how
      difficult it is for Western social scientists to move beyond pathology-based
      thinking; most authors represented here regard health primarily as the absence of
      disease. Still, these papers articulate and address questions key to
      understanding health in and of itself, including: How is health conceptualized?
      What kinds of social conditions lead to health? And, how do social inequalities
      affect health? This introduction critically discusses previous work on the
      subject to contextualize the original research papers offered here.

PMID- 15950088
TI  - The value of a critical ethnographic engagement: comments on the social
      production of health.

PMID- 15950089
TI  - Evolutionary, historical and political economic perspectives on health and
      disease.
AB  - The origin and rise of social inequalities that are a feature of the post
      Neolithic society play a major role in the pattern of disease in prehistoric and
      contemporary populations. We use the concept of epidemiological transition to
      understand changing ecological relationships between humans, pathogens and other
      disease insults. With the Paleolithic period as a baseline, we begin with
      ecological and social relationships that minimized the impact of infectious
      disease. Paleolithic populations would have retained many of the pathogens that
      they shared with their primate ancestors and would have been exposed to zoonoses
      that they picked up as they adapted to a foraging existence. The sparse mobile
      populations would have precluded the existence of endemic infectious disease.
      About 10,000 years ago, the shift to an agricultural subsistence economy created
      the first epidemiological transition, marked by the emergence of infections, a
      pattern that has continued to the present. Beginning about a century ago, some
      populations have undergone a second epidemiological transition in which public
      health measures, improved nutrition and medicine resulted in declines in
      infectious disease and a rise in non-infectious, chronic and degenerative
      diseases. Human populations are entering the third epidemiological transition in
      which there is a reemergence of infectious diseases previously thought to be
      under control, and the emergence of novel diseases. Many of the emerging and
      reemerging pathogens are antibiotic resistant and some are multi-antibiotic
      resistant. Inequality continues to widen within and between societies,
      accelerating the spread of emerging and reemerging diseases.

PMID- 15950090
TI  - When "health" is not enough: societal, individual and biomedical assessments of
      well-being among the Matsigenka of the Peruvian Amazon.
AB  - Although biomedical indicators of health status show that physical health for the
      Matsigenka of the Peruvian Amazon has significantly improved over the past 20-30
      years, the Matsigenka perceive their health and well-being to have severely
      declined during this period. This discrepancy between empirical measures and
      local perceptions of health and well-being points to the central tension inherent
      in measuring and defining "health." While biomedical parameters of health are
      generally linked to notions of the body free of illness, measurable by
      physiological means, the Matsigenka define physical health as only one component
      of what it means to be healthy and to experience well-being. For the Matsigenka,
      notions of health and well-being are linked fundamentally to ideals about
      happiness, productivity and goodness, in addition to biomedical health. The
      Matsigenka attribute the decrease in their well-being to newly instigated sorcery
      and stressors resulting from outside influences and morality institutionalized by
      cultural "outsiders", such as missionaries, school teachers, health personnel,
      oil company employees and government officials. This article explores the
      relationships between biomedical, societal and personal assessments of health and
      well-being among the Matsigenka as they seek to preserve their sense of wellness
      in spite of their rapidly changing social and economic environment. By using
      longitudinal qualitative and quantitative ethnographic and health data, this
      paper shows that, for the Matsigenka, increases in acculturation and permanent
      settlement result in an alarming decrease in their health and well-being.

PMID- 15950091
TI  - Vital warmth and well-being: steambathing as household therapy among the Tzeltal
      and Tzotzil Maya of highland Chiapas, Mexico.
AB  - Among the Maya, the cultural history of steambathing spans more than two
      millennia. Although it has largely disappeared from the lowlands, household-level
      steambathing persists in several highland Maya communities in Chiapas, Mexico. In
      this article, I present an overview of therapeutic steambathing among the Tzeltal
      and Tzotzil Maya. Through an extended discussion of the beliefs and practices
      surrounding steambathing, I develop several features of highland Maya thinking
      about physical health and "well-being". In particular, I examine a set of
      ethnophysiological representations relating to the "thermal" nature of functional
      bodies, and the relationship of these models to the maintenance and restoration
      of health. The highland Maya have articulated an elaborate understanding of
      physical health and well-being coded in an idiom of "vital warmth", and directed
      toward the preservation and augmentation of the endogenous heat necessary for
      vitality and vigor. These models simultaneously reflect empirical understandings
      of bodily states in health and illness, as well as metaphorical assumptions about
      the thermal nature of functional psychosocial identities. Steambathing draws on
      and reinforces these models, constituting a core cultural technology for
      radically altering the thermal state of the patient, an experience which the
      highland Maya regard as deeply beneficial. The paper closes with a discussion of
      recent biomedical research into the physiological effects of hyperthermal
      therapies.

PMID- 15950092
TI  - "What's wrong with me?": cervical cancer in Venezuela--living in the borderlands
      of health, disease, and illness.
AB  - Social scientists concerned with studying the social and cultural meaning of
      illness problematize the relationship between disease and illness, noting that
      illness can exist without disease-abnormal physical changes in the body. What has
      received less attention is the existence of disease-made visible through
      technological advances-in the absence of illness. Cervical cancer (or the more
      ambiguous cervical abnormalities) is an example of a disease that is largely
      symptomless in its early stages and can occur in the absence of illness. In this
      paper I explore how women seek to understand and negotiate cervical cancer in the
      context of their everyday lives, as they are confronted with seemingly disparate
      and contradictory physical and psychological states of well-being, sickness, and
      disease. This experience is what I call living on the borderlands of health,
      disease, and illness, where all of these states are experienced concurrently and
      boundaries between them blur. Through observations of patient-doctor
      interactions, ethnographic interviews with doctors and women seeking treatment
      for cervical cancer and pre-cancerous abnormalities, I analyze how women try to
      understand their medical experience. And they do so with the added challenge of
      little information being shared with them by the doctors who treat them. While
      patients do not ask many questions of their doctors, this does not mean that
      women are disinterested in their health. In fact, they develop strategies for
      eliciting clinical information about their medical conditions and actively seek
      to make sense of their experiences. By problematizing the concepts of health,
      disease, and illness, and avoiding the tendency to see these as distinct and
      contradictory phenomenon, we can gain a better understanding of their
      interrelatedness, and how people negotiate this borderland.

PMID- 15950093
TI  - The call to life: revitalizing a healthy Hawaiian identity.
AB  - The meaning of health is typically defined as the absence of disease. This
      definition, while highlighting our ability to measure the physiological
      attributes of health through morbidity and mortality statistics in turn obscures
      alternative meanings of health. In this paper, I ask three questions about the
      meaning of health. First, is health simply the body without disease? Second, are
      there alternative meanings of health that are not solely informed by
      Enlightenment views of science and biomedicine? Third, in what ways does health
      give meaning to and inform social orders and our place within them? Drawing on
      interviews with Native Hawaiians conducted on the islands of Maui and Hawaii,
      this paper examines what it means to be a "healthy Hawaiian", and in doing so,
      problematizes meanings of health. For those I interviewed, definitions of health
      were embedded in understandings of what it means to be a Native Hawaiian and
      presented an opportunity to talk about the cultural and material dispossession of
      Native Hawaiians. These definitions also remind the present generation of the
      vitality of their ancestors. In remembering the life, health and subsequent
      dispossession of Hawaiian ancestors, contemporary Hawaiians are provided with an
      alternative definition of what it means to be a "healthy Hawaiian", thus raising
      serious questions about "health" as defined by biomedicine and how best to
      achieve it. This case illustrates how a focus on concepts of health elucidates
      the relationship between health and inequality as well as Native Hawaiian's
      agency in charting a positive direction for health that has meaning in the
      everyday life of Hawaiians.

PMID- 15950094
TI  - Desperately seeking "normal": the promise and perils of living with kidney
      transplantation.
AB  - Organ transplantation offers a dramatic example of the promises for health held
      out by biomedicine-and thus, a productive vantage point from which to interrogate
      those promises. Drawing on ethnographic research on kidney transplantation in
      Guadalajara, Mexico, this article examines the version of "health" offered to
      patients through transplantation. The paper explores patients' transplant
      trajectories as they move from learning to desire a transplant to actually
      receiving one and living with it over the long term, all within particular
      structuring sociocultural and political economic conditions. The article analyzes
      how transplanted patients are forced to come to terms with the contingent states
      of "health" and "normality" wrought by transplantation as they carve out an
      existence in the persistently liminal spaces between the roles of "sick" and
      "healthy," dependent patient and fully contributing family member.

PMID- 15950095
TI  - Coca-colonization of diets in the Yucatan.
AB  - Over the past three decades, tourism-based economic development has transformed
      social and economic conditions in the Yucatan Peninsula, Mexico. Mayan
      communities have become directly involved in the changing economy as the main
      source of inexpensive labor for construction and service jobs at tourism centers,
      and as sites of ecotourism and archeotourism. In this paper, we address how these
      macro-processes of change intersect locally with the commoditization of food
      systems, diets and nutrition in four Yucatec Mayan communities with differing
      relationships to the tourist economy. Yucatec Mayan diets have become
      increasingly dependent on purchased foods, and reflect a greater consumption of
      commercialized processed foods. Coca-Cola, an international icon of US culture,
      along with other local and internationally owned calorie-dense but nutrient-poor
      snack foods, is now a common element of Mayan diets, leading to what we call
      "coca-colonization." The consequences of this diet, likely exacerbated by the
      increased consumption of snack foods, include an apparent increase in overweight
      and obese adults as well as signs of growth stunting in children. The Maya we
      talked with recognize both the potential disruption that tourism brings to all
      aspects of their lives and the necessity of jobs that tourism creates to meet
      their families' basic needs.

PMID- 15950096
TI  - Receding horizons of health: biocultural approaches to public health paradoxes.
AB  - Worldwide challenges to health reflect a "paradox of success," whereby both the
      strengths and the weaknesses of current approaches in public health,
      epidemiology, and biomedicine have determined the nature of the health problems
      we now face. In detail, we analyze and illustrate five constituent paradoxes that
      fuel continued health risk even in the face of success, including: (1) unmasking,
      (2) local biology, (3) socialization, (4) emerging and reemerging disease, and
      (5) savage inequity. We trace the pathways behind the paradoxes and their effects
      on health, and demonstrate that biocultural dynamics are involved in each.
      Furthermore, we track the roots of health paradox to changes that divert or
      disrupt pathways for production of health. These analyses contribute to an
      emerging literature of research and praxis on integrative biocultural models of
      health.

PMID- 15950097
TI  - Bone marrow imaging in MRI.

PMID- 15950098
TI  - Differential diagnosis of focal and diffuse neoplastic diseases of bone marrow in
      MRI.
AB  - Magnetic resonance imaging (MRI) has become the preferred imaging modality for
      the evaluation of malignant disease in the bone marrow. Compared to bone marrow
      aspiration and biopsy, MRI is noninvasive and provides information by sampling a
      large volume of bone marrow. Due to disease-related alterations in the
      composition of bone marrow, MRI provides a very high sensitivity, but lacks
      specificity for most bone marrow disorders. However, MRI can be a very valuable
      diagnostic tool properly placed within the clinical context.

PMID- 15950099
TI  - Whole-body MR imaging of bone marrow.
AB  - In clinical routine, multimodality algorithms, including X-ray, computed
      tomography, scintigraphy and MRI, are used in case of suspected bone marrow
      malignancy. Skeletal scintigraphy is widely used to asses metastatic disease to
      the bone, CT is the technique of choice to assess criteria of osseous destruction
      and bone stability. MRI is the only imaging technique that allows direct
      visualization of bone marrow and its components with high spatial resolution. The
      combination of unenhanced T1-weighted-spin echo- and turbo-STIR-sequences have
      shown to be most useful for the detection of bone marrow abnormalities and are
      able to discriminate benign from malignant bone marrow changes. Originally, whole
      body MRI bone marrow screening was performed in sequential scanning techniques of
      five body levels with time consuming coil rearrangement and repositioning of the
      patient. The introduction of a rolling platform mounted on top of a conventional
      MRI examination table facilitated whole-body MR imaging and, with the use of fast
      gradient echo, T1-weighted and STIR-imaging techniques, for the first time
      allowed whole-body imaging within less than one hour. With the development of
      parallel imaging techniques (PAT) in combination with global matrix coil
      concepts, acquisition time could be reduced substantially without compromises in
      spatial resolution, enabling the implementation of more complex and flexible
      examination protocols. Whole-body MRI represents a new alternative to the
      stepwise multimodality concept for the detection of metastatic disease, multiple
      myeloma and lymphoma of the bone with high diagnostic accuracy.

PMID- 15950100
TI  - Diagnostic value of MRI in comparison to scintigraphy, PET, MS-CT and PET/CT for
      the detection of metastases of bone.
AB  - The initial localization of metastases in the bone in patients with solid tumors
      has a relatively good prognosis in comparison with visceral metastasization. The
      early detection of bone marrow metastases allows for a rapid initiation of
      therapy and a subsequent reduction in the morbidity rate. Modern MRI is superior
      to the 30-year-old skeletal scintigraphy and bone marrow scintigraphy with
      respect to sensitivity, specificity, as well as the extent of osteal metastasis.
      MRI provides substantial, therapy-relevant additional information. MSCT plays an
      important role in the management of cancer patients in clinical routine and gives
      an excellent survey of the axial skeleton by demonstrating osteolytic and
      osteoblastic metastases. Extensive comparative studies of MRI with 18F-FDG-PET
      and 18F-fluoride-PET have not yet been carried out. Whole body MRI is a very
      promising new staging method for the oncological diagnosis of solid tumors and
      the detection of osteal metastases. The adoption of 18F-FDG-PET and 18F-fluoride
      PET FDG as well as the side by side PET-CT image fusion and the two in one PET/CT
      examinations appears to be slightly less sensitive to whole body MRI in the
      detection of osteal metastases. Larger, prospective multicenter studies are
      necessary to establish these as new, promising methods for the detection of
      osteal metastases.

PMID- 15950101
TI  - Role of MRI for the diagnosis and prognosis of multiple myeloma.
AB  - For the correct staging of patients with multiple myeloma sensitive detection is
      mandatory in order to estimate prognosis and to decide for adequate therapy.
      Magnetic resonance imaging (MRI) is superior to radiography for both, focal and
      diffuse involvement. Five different infiltration patterns can be differentiated:
      (1) normal appearance of bone marrow despite minor microscopic plasma cell
      infiltration, (2) focal involvement, (3) homogeneous diffuse infiltration, (4)
      combined diffuse and focal infiltration, (5) "salt-and-pepper"-pattern with
      inhomogeneous bone marrow with interposition of fat islands. For the fast and
      complete assessment of all patterns a combination of a T1-weighted spin echo
      sequence and a fat suppression technique should be employed. The focal
      involvement is clearly demonstrated as areas of high signal intensity on, e.g.
      STIR images. Diffuse involvement is best detected on unenhanced T1-weighted SE
      sequences and it manifests as homogeneous signal reduction. It can be quantified
      objectively by calculation of the percentage of signal intensity increase after
      contrast material injection. With parallel imaging and special coil devices, such
      as total imaging matrix (Siemens systems, Avanto) a "screening" of the whole red
      bone marrow as for myeloma infiltration is possible within a reasonable time.
      Patients without bone marrow infiltration have a significantly longer survival
      than patients with bone marrow infiltration in MRI at the time of diagnosis.
      However, even in stage I disease (Durie and Salmon) and negative X-ray films bone
      marrow infiltration in MRI may be detected in 29-50% of patients. Those patients
      typically show an earlier disease progression. Recently, MRI has been implemented
      in the clinical staging of patients with multiple myeloma. MRI may also monitor
      response to therapy. Signs of good response in cases with focal involvement are:
      reduction of signal intensity on T2-weighted spin echo images, lack or rim-like
      enhancement after contrast material injection or even a normalisation of bone
      marrow signal. In case of diffuse involvement a partly patchy reconversion to
      fatty marrow can be seen.

PMID- 15950102
TI  - Techniques for diffusion-weighted imaging of bone marrow.
AB  - Diffusion-weighted magnetic resonance imaging (DWI) is an imaging technique which
      is sensitive to random water movements in spatial scales far below those
      typically accessible by magnetic resonance imaging (MRI). This property makes DWI
      a powerful tool for diagnosis of diseases which involve alterations in water
      mobility, such as acute stroke. In bone marrow, DWI has been proven to be a
      highly useful method for the differential diagnosis of benign and malignant
      compression fractures. Unfortunately, the application of DWI sequences to the
      bone marrow frequently suffers from artifacts, which in some cases seriously
      restrict the diagnostic utility of the image. This requires the introduction of
      additional correction techniques, or even the development of new sequences. Thus,
      the selection of an adequate imaging technique for DWI of the bone marrow is a
      very important issue. In this article the most important sequences for DWI of the
      bone marrow are reviewed. Special attention is paid to the problems associated
      with these sequences, as well as their possible solutions.

PMID- 15950103
TI  - Ectopic posterior pituitary high signal in preoperative and postoperative
      macroadenomas: dynamic MR imaging.
AB  - BACKGROUND AND PURPOSE: In patients with macroadenoma, posterior pituitary high
      signal (PPHS) on T1-weighted magnetic resonance (MR) imaging is sometimes
      observed in an ectopic location. The present study compared incidences of ectopic
      PPHS before and after macroadenoma surgery using MR imaging, including dynamic MR
      imaging to ascertain whether this ectopic change is irreversible. MATERIALS AND
      METHODS: MR imaging was performed preoperatively in 111 cases of macroadenoma,
      and then repeated more than 1-year postoperatively in 47 patients. Enhancement of
      PPHS was assessed using dynamic MR imaging. Areas of enhanced hyperintensity were
      considered true PPHS, and the relationship between presence and location of true
      PPHS and adenoma volume was analyzed. Moreover, changes in the presence and
      location of true PPHS were ascertained among the patients who underwent
      postoperative follow-up MR imaging. RESULTS: Preoperatively, PPHS was seen only
      in the normal location in 29 patients (Group A: 26.1%). High signal was detected
      only in an ectopic location in 58 patients, and early enhancement of this ectopic
      high signal was confirmed by dynamic MR imaging in 56 patients (Group B: 50.5%).
      No PPHS was observed in 24 patients (Group C: 21.6%). Adenoma volume was
      significantly greater for Group B than for Group A (p<0.001). Among the Group B
      patients who underwent MR imaging postoperatively (n=31), the location of PPHS
      was not changed, except for two patients in whom PPHS was absent.
      Postoperatively, PPHS was not observed in the normal location in any patient in
      the Group B. CONCLUSIONS: Greater volume of adenoma is associated with a higher
      incidence of ectopic PPHS, and the ectopic change is irreversible.

PMID- 15950104
TI  - Intracranial aneurysms: reproduction of the surgical view using 3D-CT
      angiography.
AB  - Our purpose was to describe a technique for simulating the surgical view of
      ruptured intracranial aneurysms, using volume-rendering techniques in spiral
      computed tomography (CT) angiography data. The 3D (three-dimensional) rendered
      images were assessed by a team consisted of four radiologists, one neurosurgeon
      and one medical physicist. The resultant 'surgical view' image was standardized
      in space using a three-dimensional coordinate system, which allowed for its
      reproduction in the operating theatre. The surgical views are a potentially
      useful tool for the surgical planning of intracranial aneurysms.

PMID- 15950105
TI  - In vivo 1H MR spectroscopic findings in traumatic contusion of ICR mouse brain
      induced by fluid percussion injury.
AB  - PURPOSE: The purpose of this study was to investigate the proton metabolic
      differences of the right parietal cortex with experimental brain contusions of
      ICR mouse induced by fluid percussion injury (FPI) compared to normal controls
      and to test the possibility that 1H magnetic resonance spectroscopy (MRS)
      findings could provide neuropathologic criteria in the diagnosis and monitoring
      of traumatic brain contusions. MATERIALS AND METHODS: A homogeneous group of 20
      ICR male mice was used for MRI and in vivo 1H MRS. Using image-guided, water
      suppressed in vivo 1H MRS with a 4.7 T MRI/MRS system, we evaluated the MRS
      measurement of the relative proton metabolite ratio between experimental brain
      contusion of ICR mouse and healthy control subjects. RESULTS: After trauma,
      NAA/Cr ratio, as a neuronal marker decreased significantly versus controls,
      indicating neuronal loss. The ratio of NAA/Cr in traumatic brain contusions was
      0.90+/-0.11, while that in normal control subjects was 1.13+/-0.12 (P=0.001). The
      Cho/Cr ratio had a tendency to rise in experimental brain contusions (P=0.02).
      The Cho/Cr ratio was 0.91+/-0.17, while that of the normal control subjects was
      0.76+/-0.15. However, no significant difference of Glx/Cr was established between
      the experimental traumatic brain injury models and the normal controls.
      DISCUSSION AND CONCLUSIONS: The present 1H MRS study shows significant proton
      metabolic changes of parietal cortex with experimental brain contusions of ICR
      mouse induced by FPI compared to normal controls. In vivo 1H MRS may be a useful
      modality for the clinical evaluation of traumatic contusions and could aid in
      better understanding the neuropathologic process of traumatic contusions induced
      by FPI.

PMID- 15950106
TI  - MR of 2270 TMJs: prevalence of radiographic presence of otomastoiditis in
      temporomandibular joint disorders.
AB  - OBJECTIVE: The purpose of this study is to determine the prevalence of
      radiographic presence of otomastoiditis while examining temporomandibular joint
      (TMJ) disorders in magnetic resonance images (MRI) in a series of 2270
      temporomandibular joint magnetic resonance images and to examine the relationship
      between otomastoiditis and TMJ disorders. MATERIALS AND METHODS: 2270
      temporomandibular joint magnetic resonance images and patients' data were
      retrospectively investigated. Magnetic resonance images were obtained from the
      patients who referred to Osaka University Dental Hospital Outpatient Clinic with
      TMJ complaints for the last four years (from January 1998 to January 2003). The
      patients, who were diagnosed as otomastoiditis based on their temporomandibular
      joint magnetic resonance images, were sent to Osaka University Hospital
      Department of Otolaryngology for a medical consultation in order to have their
      pathologies certified following their MR process. Age and sex were recorded for
      all patients and for otomastoiditis cases; location of the disease, symptoms of
      patients and TMJ findings were noted as well. RESULTS: Seven patients were
      diagnosed as acute otomastoiditis and one patient diagnosed as chronic active
      otitis media with cholesteatoma in the series of 2270 MR, which were representing
      a prevalence of 0.39%. Neurilemoma diagnosed in left mastoid process in one
      patient. The final diagnoses of all patients were made after medical
      consultation. CONCLUSION: While examining temporomandibular joint magnetic
      resonance images; it is not only important to examine just the TMJ structures,
      but also to look at the nearby anatomical features to check evidence for
      inflammatory disease.

PMID- 15950107
TI  - CT and MR imaging features of oral and maxillofacial hemangioma and vascular
      malformation.
AB  - PURPOSE: To present CT and MR images and compare CT and MRI features of oral and
      maxillofacial hemangioma and vascular malformation. MATERIAL AND METHODS: The
      clinical materials consisted of nine vascular tumors from nine patients examined
      by both CT and MR scanners between November 1996 and March 2002. Both CT and MR
      images were retrospectively evaluated. The following features were evaluated:
      detectability of the lesion, border of the lesion, tumor margin, inner nature of
      the lesion, contrast between the lesion and surrounding tissues, degree of CT
      value or signal intensity of the lesion, enhancement of contrast medium, inner
      nature of the lesion after contrast medium injection, detectability of
      phleboliths and detectability of bone resorption. RESULTS: In two patients, we
      could not detect lesions in any of the CT images because of artifacts from the
      teeth and/or dental restorations. In contrast, we could detect all lesions on T2
      weighted MR images and contrast enhanced T1-weighted MR images. On T2-weighted
      images with the fat suppression technique, tumors tended to show higher contrast
      compared to surrounding tissues. CONCLUSION: T2-weighted images with the fat
      suppression technique and contrast enhanced T1-weighted images with the fat
      suppression technique were very useful for the detection of vascular lesions.
      Observation from optional directions (axial, coronal and sagittal images) seemed
      appropriate for delineating the extension of the tumor. Phleboliths detectability
      on CT images was superior to that on MR images.

PMID- 15950108
TI  - Colour Doppler ultrasound assessment of well-functioning mature arteriovenous
      fistulas for haemodialysis access.
AB  - BACKGROUND: A well-functioning mature arteriovenous fistula is essential for the
      maintenance of haemodialysis in patients with chronic renal failure. The Brescia
      Cimino arteriovenous fistula has the best survival characteristics and low rate
      of complications. The most common reason of fistula failure is thrombosis caused
      by stenosis. Colour Doppler ultrasonography has proven to be effective in the
      assessment of anatomical vascular features. The majority of studies were done in
      patients with clinically presumed arteriovenous fistula complications. However,
      only limited data are available about the well-functioning mature arteriovenous
      fistulas. The purpose of the present study was to evaluate completely
      asymptomatic, mature arteriovenous fistulas with colour Doppler ultrasound.
      MATERIALS AND METHODS: From July 2001 to April 2003, we examined 139 patients
      with the end-stage renal disease. They were in the range of 19-79 years of age
      (mean, 46.7 years). The study included only the patients who met the following
      criteria: (1) no difficulties with haemodialysis (as reported by nurses); (2)
      normal venous diastolic blood pressure (<150 mmHg) at monthly evaluation; (3)
      normal urea clearance x time/urea volume of distribution; (4) blood cells count,
      plasma electrolytes, and liver function at monthly evaluation. The mean fistula
      age was 26 months (S.D.=21.9). The mean time of dialysis therapy was 49 months.
      Thirty-eight percent patients had primary fistulas, 23%--secondary, 11%--third
      and 11%--fourth, 4%--fifth, 5%--sixth, and 8% patients had more than sixth.
      RESULTS: There was no correlation between: (1) patient's age and fistula age; (2)
      patient's age and number of fistulas in one patient; (3) fistula age and number
      of fistulas in one patient; (4) localization of fistula and fistula age. There
      was a strong correlation between dialysis therapy period and number of fistulas
      in one patient. The mean flow volume was 1204.1 ml/min (S.D.=554). It was
      significantly higher in the fistulas with aneurysms, calcifications and tortuous
      vessels and lower in those with stenosis. There was no correlation between the
      flow volume or presence of stenosis and fistula age. Stenosis was detected in 64%
      fistulas. Fifty-seven percent of stenoses were located in the anastomotic region,
      22% stenoses were in vein junction, 19% were at one or both ends of aneurysm, and
      2% in the remaining region of the efferent vein. Perivascular colour artefacts
      were present at the 94% fistulas with stenosis. Chronic venous occlusion with
      collateral veins was detected in 6% of fistulas. The aneurysms were observed in
      54% fistulas. The mean diameter of aneurysms was 12.4 mm. Ninety-six percent of
      aneurysms were located at puncture sites. Ten patients had a small thrombus in an
      aneurysm and at puncture sites. CONCLUSIONS: We conclude that there was a high
      level of abnormalities present in well-functioning mature arteriovenous fistulas.
      However, these abnormalities were not sufficient to affect the functioning of the
      dialysis fistula.

PMID- 15950109
TI  - Comparison of transjugular intrahepatic portosystemic shunt dysfunction in PTFE
      covered stent-grafts versus bare stents.
AB  - PURPOSE: The aim was to compare the clinical and hemodynamic outcome between
      polytetrafluoroethylene (PTFE)-coated stent-grafts and bare stents in patients
      who required both elective and emergency transjugular intrahepatic portosystemic
      shunt (TIPS) placement due to portal hypertension related complications.
      MATERIALS AND METHODS: Retrospective analysis of all seventy patients with portal
      hypertension related complications who required TIPS placement in a referral
      hospital from September 1998 to May 2002 was done. Follow-up was extended until
      May 2003. PTFE-covered stent-grafts were used in the latter 20. Demographic
      variables, cirrhosis etiology and Child-Pugh class, indication of TIPS placement
      and clinical outcome were recorded. The following TIPS-related outcomes were
      registered: recurrent variceal bleeding and/or ascites, hepatic encephalopathy
      and mortality. RESULTS: Baseline characteristics, portacaval gradient (PCG) after
      TIPS placement and at 1 month angiographic revision were similar in both groups.
      At 6 month follow-up, PCG was significantly lower in patients with stent-grafts
      (14.2 mmHg (5.6 mmHg) versus 7 mmHg (1 mmHg), p<0.001). Overall, there were no
      cases of clinically relevant TIPS dysfunction in the coated stent group while 22%
      of patients in the bare stent group had recurrence of portal hypertension related
      complications (p=0.085). Actuarial probability of TIPS dysfunction in bare stents
      was 82% at 12 months compared to no episode in covered stent-grafts (p=0.03).
      Mean increase in total serum bilirubin was higher in the PTFE-coated stent group
      (6.7 mg/dl (14.4 mg/dl) versus 0.5 mg/dl (2.4 mg/dl), p=0.01) without differences
      in encephalopathy nor mortality rate. CONCLUSION: One year shunt patency rate is
      improved with placement of ePTFE-covered stent-grafts without a higher rate of
      encephalopathy. Further prospective trials are required.

PMID- 15950110
TI  - US-guided placement of temporary internal jugular vein catheters: immediate
      technical success and complications in normal and high-risk patients.
AB  - OBJECTIVE: To evaluate the technical success and immediate complication rates of
      temporary internal jugular vein (IJV) haemodialysis catheter placement in normal
      and high-risk patients. METHODS AND MATERIALS: Two-hundred and twenty temporary
      internal jugular vein catheters inserted under ultrasound guidance in 172
      patients were prospectively analyzed. Of 172 patients, 93 (54%) were males and 79
      (46%) were females (age range, 18-83; mean, 56.0 years). Of 220 catheters, 171
      (78%) were placed in patients who had a risk factor for catheter placement like
      patients with disorder of haemostasis, poor compliance, and previous multiple
      catheter insertion in the same IJV. Forty-seven (21.3%) procedures were performed
      on bed-side. A catheter was inserted in the right IJV in 178 procedures (80.9%)
      and left IJV in 42 procedures. Of 172 patients, 112 (65%) had only one catheter
      placement and the rest had had more than one catheter placement (range, 1-5).
      RESULTS: Technical success was achieved in all patients (100%). Average number of
      puncture was 1.24 (range, 1-3). One hundred and eighty-three insertions (83.1%)
      were single-wall punctures, whereas 37 punctures were double wall punctures. Nine
      (4%) minor complications were encountered. Inadvertent carotid artery puncture
      without a sequel in four procedures (1.8%), oozing of blood around the catheter
      in three procedures (1.4%), a small hematoma in one procedure (0.4%), and
      puncture through the pleura in one procedure (0.4%) without development of
      pneumothorax. Oozing of blood was seen only in patients with disorder of
      haemostasis. CONCLUSION: Ultrasound-guided placement of internal jugular vein
      catheters is very safe with very high success rate and few complications. It can
      safely be performed in high-risk patients, like patients with disorders of
      haemostasis and patients with previous multiple catheter insertion in the same
      vein.

PMID- 15950111
TI  - HVS-based medical image compression.
AB  - INTRODUCTION: With the promotion and application of digital imaging technology in
      the medical domain, the amount of medical images has grown rapidly. However, the
      commonly used compression methods cannot acquire satisfying results. METHODS: In
      this paper, according to the existed and stated experiments and conclusions, the
      lifting step approach is used for wavelet decomposition. The physical and
      anatomic structure of human vision is combined and the contrast sensitivity
      function (CSF) is introduced as the main research issue in human vision system
      (HVS), and then the main designing points of HVS model are presented. On the
      basis of multi-resolution analyses of wavelet transform, the paper applies HVS
      including the CSF characteristics to the inner correlation-removed transform and
      quantization in image and proposes a new HVS-based medical image compression
      model. RESULTS: The experiments are done on the medical images including computed
      tomography (CT) and magnetic resonance imaging (MRI). At the same bit rate, the
      performance of SPIHT, with respect to the PSNR metric, is significantly higher
      than that of our algorithm. But the visual quality of the SPIHT-compressed image
      is roughly the same as that of the image compressed with our approach. Our
      algorithm obtains the same visual quality at lower bit rates and the
      coding/decoding time is less than that of SPIHT. CONCLUSIONS: The results show
      that under common objective conditions, our compression algorithm can achieve
      better subjective visual quality, and performs better than that of SPIHT in the
      aspects of compression ratios and coding/decoding time.

PMID- 15950112
TI  - [Tracheotomy in brain injured patients: which patients? Why? When? How?].
AB  - The aim of this study is to determine, from the data available in the literature,
      the indications of tracheostomy in brain injured patients, the incidence and risk
      factors for complications and the follow-up required until decannulation. The
      incidence of tracheostomy is 10% in TBI and 50 to 70% in subpopulations with a
      Glasgow Coma Scale (GCS) below 9. Early complications are not specific. The most
      frequent late complication is laryngotracheal stenosis, which occurs in 15% and
      is more frequently observed in the most severe patients with major hypertonia. It
      is likely that tracheostomy, if needed, should be performed early and the
      prognosis as to whether it will be required, can be made at the end of the first
      week. The follow-up of these patients includes surveillance of multiresistant
      colonisations and systematic performance of fibroscopy before decannulation.
      Cuffless, small diameters, soft tracheostomy tubes, are preferred on the long
      term unless the risk of aspiration remains high.

PMID- 15950113
TI  - [Spasticity. Physical therapy, preventive measures and treatment].
AB  - Spasticity is one of the most common motor and tonus disorders during the initial
      phase with traumatic brain injured patients. The evaluation of spasticity is
      mainly clinical but it is very important to prevent complications such as
      limitation of range of motion, pain, decubitus ulcers. The therapeutic options
      consist in classical indications such as baclofen, dantrolene, tizanidine,
      benzodiazepine, associated with physiotherapy. Other additive therapeutic options
      could be discussed: use of toxin botulinum in focal spasticity and intrathecal
      baclofen infusion in case of severe spasticity (often associated with
      dysautonomic disorders.).

PMID- 15950114
TI  - [Peripheral neurolytic blocks and spasticity].
AB  - Peripheral nerve blockade is one of the therapeutic possibilities to treat
      spasticity of various muscles. Percutaneous nerve stimulation allows accurate
      location of nerves and neurolysis can be performed using intraneural injection of
      65% ethanol or 5 to 12% phenol. Spastic contraction of various muscle groups is a
      common source of pain and disability which prevents from having efficient
      rehabilitation. Test-blocks as well as neurolytic blocks are possible in most of
      motor nerves of the upper and lower limbs and main indications are spastic
      sequelae of stroke and spinal trauma but also of multiple sclerosis, cerebral
      palsy and chronic coma. The use of percutaneous nerve stimulation allows accurate
      location and four nerves are more frequently treated: pectoral nerve loop,
      median, obturator and tibial nerves. In patients with spasticity of the adductor
      thigh muscles, nerve blocks are performed via a combined approach using
      fluoroscopy and nerve stimulation to identify the obturator nerve. No
      complications occurred and minor side effects are transient painful phenomena
      during injection. These approaches proved to be accurate, fast, simple, highly
      successful and reproducible. Percutaneous neurolytic procedures should be done as
      early as possible, as soon as spasticity becomes painful and disabling in
      patients with neurological sequelae of stroke, head trauma or any lesion of the
      motor neuron.

PMID- 15950115
TI  - [Evoked potentials and post-traumatic evolution].
AB  - Visual, somatosensory, and brainstem auditory evoked potentials provide
      functional quantitative assessment of the cerebral cortex and brainstem. Their
      contribution at the acute stage of coma concerns diagnosis, prognosis, and follow
      up. Four patterns are observed in traumatic coma: pattern 1=dysfunction of the
      cerebral cortex, brainstem integrity: good prognosis in more than 80% of cases;
      pattern 2=midbrain dysfunction: prognosis depends on both the reversibility of
      midbrain dysfunction and the extent of associated axonal lesions in the
      hemispheric white matter; pattern 3=pontine dysfunction due to transtentorial
      herniation: ominous prognosis, this pattern must be early detected by continuous
      monitoring; pattern 4=brain death: we currently use evoked potentials at the only
      brain-death confirmatory test, even in sedated patients. The contribution of
      evoked potentials in vegetative or minimally responsive states concerns the
      identification of these patients whose state is determined by midbrain
      dysfunction and the evaluation of persisting cognitive abilities in individual
      cases.

PMID- 15950116
TI  - [Intensive care handling: specific expectations of rehabilitation].
AB  - For the severe head injured patients, the way of going from coma to arousal is
      considerably different from one patient to the other, and it is not always easy
      to determine the appropriate moment for taking them out of intensive care, into
      rehabilitation. This is the reason why, instead of considering these two
      treatments as successive phases, it is better to consider them as a collaboration
      process. The objective of this paper is to describe the needs of this type of
      patients, by using the data gathered on a weekly basis in the medical data
      department of the Centre Medical de l'Argentiere, on patients admitted in 2002 in
      the rehabilitation and post-intensive care departments. A typology can be defined
      with the association of three characteristics: several disabilities; physical,
      behavioural and relational impairments; need for a multidisciplinary
      rehabilitation team. This typology requires a specific rehabilitation treatment
      as from the acute phase of intensive care.

PMID- 15950117
TI  - [Ethical and legal points concerning minimally conscious state and permanent
      vegetative state].
AB  - The ethical and legal problems posed by severe outcome of coma are complex and
      their analysis requires a multi-disciplinary approach. Three aspects have been
      particularly studied in this paper. The first is a reminder of the medical
      definitions of the concepts of vegetative state and minimally conscious state.
      The second focuses on the analysis of the ethical and legal debate of these
      conditions at an international level. Finally, the third concerns the wealth
      prospects, proposed, in France, by the circular letter dated May 3, 2002.

PMID- 15950118
TI  - [Serious brain injury and public health, epidemiologic and financial
      considerations, comprehensive management and care].
AB  - The management of persons with traumatic brain injury affects a large spectrum of
      interventions from acute phase to the hospital discharge and the return to
      community. The incidence of brain injuries on mortality and morbidity constitutes
      a serious problem in front of the Health Administration. The traffic accidents
      remain the main cause but the falls in elderly are increasing. In the both cases
      preventive measures can be efficiency. In France, each year, there are about
      150,000 new cases, 8000 of them will be dead and 4000 with coma. It is likely
      that 30,000 persons are living to day with important sequela of a brain injury.
      The management requires various types of interventions, each of them with
      specific and specialized techniques. It is necessary to have an overview of the
      problem and to work together in a comprehensive network. So French Health
      Ministry has just published an official note to precise some directives and co
      ordination of the different interventions.

PMID- 15950119
TI  - [Gap junction-mediated intercellular communication in astrocytes and
      neuroprotection].
AB  - Neuroglial interaction represents a concept that is now more and more integrated
      in the attempts to understand who does what and how in neuronal processing and
      survival, in normal as well as in pathological situations. The purpose of the
      review is to provide an overlook about the role of glial cells, mainly
      astrocytes, in neuroprotection. Since a typical feature of glia is to be
      connected by gap junctions that allow them to be organized as a communicating
      network(s), we will focus this review on what is known about the contribution of
      astrocyte gap junctions (AGJ) in neuronal survival. As neuroglial interaction and
      AGJ are both affected during neurodegenerative diseases, we will also consider
      the above mentioned glial properties in a pathological context with a special
      interest in Alzheimer's disease.

PMID- 15950120
TI  - Was photosynthetic RuBisCO recruited by acquisitive evolution from RuBisCO-like
      proteins involved in sulfur metabolism?
AB  - Genome analyses have revealed that the genomes of non-photosynthetic bacteria
      including Bacillus subtilis code for proteins similar to the large subunit of
      RuBisCO (called RuBisCO-like protein (RLP)). This raises a fundamental question
      as to their functional relationship to photosynthetic RuBisCO. Recently, we
      identified the RLP of B. subtilis as the 2,3-diketo-5-methylthiopentyl-1
      phosphate enolase in the methionine salvage pathway. In this mini-review, we
      suggest functional and evolutionary links between B. subtilis RLP and
      photosynthetic RuBisCO. Furthermore, we propose that photosynthetic RuBisCOs
      evolved from RLPs similar to that found in B. subtilis.

PMID- 15950121
TI  - The PpsR regulator family.
AB  - Under aerobic conditions, phototrophic bacteria repress the formation of pigments
      to protect cells in the presence of light from the damaging effects of reactive
      oxygen species and consume oxygen through respiratory complexes. Members of the
      PpsR family regulate the transcription of bch, crt, puc, and hem genes in respond
      to redox or light conditions. This mini-review focuses on the function and
      distribution of PpsR proteins.

PMID- 15950122
TI  - Role of bacterial cell surface structures in Escherichia coli biofilm formation.
AB  - Various cell surface molecules and structures have been implicated in biofilm
      formation in Escherichia coli. This review presents an overview of the
      occurrence, production and interaction of these components, their influence at
      one or more developmental stages of biofilm formation, and their potential role
      as virulence factors in pathogenic E. coli strains.

PMID- 15950123
TI  - Effect of T- and C-loop mutations on the Herbaspirillum seropedicae GlnB protein
      in nitrogen signalling.
AB  - Proteins of the PII family are found in species of all kingdoms. Although these
      proteins usually share high identity, their functions are specific to the
      different organisms. Comparison of structural data from Escherichia coli GlnB and
      GlnK and Herbaspirillum seropedicae GlnB showed that the T-loop and C-terminus
      were variable regions. To evaluate the role of these regions in signal
      transduction by the H. seropedicae GlnB protein, four mutants were constructed:
      Y51F, G108A/P109a, G108W and Q3R/T5A. The activities of the native and mutated
      proteins were assayed in an E. coli background constitutively expressing the
      Klebsiella pneumoniae nifLA operon. The results suggested that the T-loop and C
      terminus regions of H. seropedicae GlnB are involved in nitrogen signal
      transduction.

PMID- 15950124
TI  - The relationship between inhibition of bacterial adhesion to a solid surface by
      sub-MICs of antibiotics and subsequent development of a biofilm.
AB  - Many studies have demonstrated that subminimal inhibitory concentrations (sub
      MICs) of antibiotics can inhibit initial microbial adherence to medical device
      surfaces. It has been suggested that, by inhibiting initial adhesion, biofilm
      formation might be prevented. However, since initial adherence and subsequent
      biofilm formation may be two distinct phenomena, conclusions regarding the
      effects of sub-MIC antibiotics on initial adhesion cannot be extrapolated to
      biofilm formation. In this study, we evaluated the adherence of several clinical
      isolates of coagulase-negative staphylococci (CoNS) to acrylic and the effect of
      sub-MICs of vancomycin, cefazolin, dicloxacillin and combinations of these
      antibiotics on adherence and biofilm formation. Most of the antibiotics used
      resulted in effective reduction of bacterial adherence to acrylic, in some cases
      reaching over 70% inhibition of adherence. When strains with a high biofilm
      forming capacity were grown in sub-MICs of those antibiotics, there existed
      combinations of the drugs that significantly inhibited biofilm formation.
      However, most of the antibiotic combinations that inhibited adherence did not
      have a profound effect on biofilm formation. When comparing the results of the
      effect of sub-MIC amounts of antibiotics in inhibiting adherence with their
      effect on the inhibition of biofilm formation, significant differences were
      found, mainly when using combinations of antibiotics. In general, the effect on
      the inhibition of adherence was greater than the effect on inhibiting biofilm
      formation. These results demonstrate that assays evaluating the inhibition of
      initial adherence to medical surfaces cannot fully predict the effect on
      inhibition of biofilm formation.

PMID- 15950125
TI  - Construction of a Pseudomonas sp. derivative carrying the cry9Aa gene from
      Bacillus thuringiensis and a proposal for new standard criteria to assess
      entomocidal properties of bacteria.
AB  - An isolate of Pseudomonas sp. (16S rDNA sequence 98% homologous to P. graminis
      and P. lutea) was isolated from the phyllosphere of black pine in northern Italy
      and used as a host for the gene encoding the Cry9Aa entomocidal toxin from
      Bacillus thuringiensis subsp. galleriae. An expression system featuring a
      synthetic highest-consensus promoter specifically tailored for the regulated
      induction of cloned genes over a broad range of Gram-negative bacteria was used
      to drive the production of the introduced toxin. The construct showed effective
      toxicity toward larvae of the greater wax moth (Galleria mellonella), which was
      also used as a model insect for establishing a number of newly proposed toxicity
      indices (LC50 cellular efficiency, toxin cellular efficiency, GMO efficiency,
      lethal cellular intake). These were devised in order to express toxicities of
      entomocidal bacteria in a standard fashion enabling the fine tuning of biocontrol
      treatments as well as the comparative evaluation of different reports.

PMID- 15950126
TI  - Identification by two-dimensional electrophoresis of a new adhesin expressed by a
      low-passaged strain of Mycoplasma bovis.
AB  - A significant decrease in adherence rates of Mycoplasma bovis to bovine bronchial
      epithelial (BBE) cells has been observed after passage of the organism in
      artificial medium. Analysis of the proteins expressed by M. bovis isolate 2610 by
      two-dimensional (2-D) electrophoresis demonstrated differences between the cells
      harvested after the 7th and 116th passage. Three silver-stained prominent spots
      observed in 2-D electrophoretic separation of protein extracts of the lower
      passaged cells were considerably less strongly expressed in the sample from
      higher-passaged cells. These spots had a molecular mass of approximately 24 kDa
      and an isoelectric point of about 5. The mass spectrometry analysis of these
      trypsin-sensitive proteins led to their identification as a unique new member of
      the Vsps family of membrane-associated proteins. Serum from a mouse immunized
      with these proteins significantly reduced adherence of M. bovis to BBE cells.
      This result underlines the function of this new Vsp in adherence of M. bovis to
      host cells.

PMID- 15950127
TI  - An extracellular protease from Brevibacillus laterosporus G4 without parasporal
      crystals can serve as a pathogenic factor in infection of nematodes.
AB  - Brevibacillus laterosporus is an aerobic spore-forming bacterium with the ability
      to produce canoe-shaped lamellar parasporal inclusions adjacent to spores. An
      isolate named G4 was identified as a B. laterosporus which does not produce
      parasporal crystals and shows significant toxic activity toward nematodes. Crude
      extracellular protein extract from culture supernatant of B. laterosporus G4
      killed the nematodes within 12 h and finally destroyed the targets within 24 h,
      which suggested possible proteinaceous pathogeny. A homogeneous extracellular
      protease with nematicidal activities, purified by chromatography, confirmed the
      hypothesis that it might serve as a pathogenic factor during infection of the G4
      strain. Characterization of the purified protease revealed a molecular mass of 30
      kDa and optimum activity at pH 10 and 50 degrees C. The protease hydrolyzed
      relatively broad substrates including collagen and the cuticle of nematodes, and
      histopathological observations demonstrated the resulting destroyed nematode
      cuticle upon treatment by purified protease. Our present study reveals that
      extracellular protease, but not previously reported parasporal crystals, can be
      employed in infection against invertebrates by the B. laterosporus G4 strain.

PMID- 15950128
TI  - Inv-mediated apoptosis of epithelial cells infected with enteropathogenic
      Yersinia: a protective effect of lactoferrin.
AB  - Yersinia spp., Gram-negative bacteria infecting animals and humans, contain
      plasmid and chromosomal genes coding for different virulence factors, of which
      outer membrane proteins are the most important. Among these, the inv gene product
      allows bacterial adherence and penetration of cells exposed at the intestinal
      lumen surface, and subsequent colonization of lymph nodes. In this research, we
      have studied the effects of bovine lactoferrin (bLf) on Y. enterocolitica and Y.
      pseudotuberculosis Inv-mediated interactions with epithelial cells. In
      particular, we analyzed bLf activity toward adhesion, invasion, and cell death
      induction by Yersinia spp. and the Escherichia coli HB101 (pRI203) strain
      (expressing the cloned Yersinia inv gene). Results showed that bLf was
      ineffective in bacterial adhesivity and invasivity whereas it inhibited apoptosis
      with a dose-dependent relationship. As epithelial cell apoptosis helps
      enteropathogenic Yersinia to attack the host and to gain access to the tissue,
      our results demonstrate a new potential antimicrobial application for bLf.

PMID- 15950129
TI  - Displacement of epsilon-proteobacterial core genes by horizontally transferred
      homologous genes.
AB  - The introduction of novel genes by horizontal gene transfer (HGT) is considered
      an alternative mechanism for genetic adaptation, leading to diversification and
      speciation. The goal of this study was to determine which genes that are present
      in all sequenced epsilon-proteobacterial genomes were acquired by HGT. In our
      approach we used BLAST analysis to reduce the number of genes that subsequently
      needed to be analysed using more in-depth phylogenetic methods, including
      neighbour-joining and maximum likelihood. Among the 991 core genes found in all
      five completed epsilon-proteobacterial genome sequences, we identified 30 genes
      that were probably acquired by HGT. It is proposed that these genes displaced an
      ancestral core gene with a similar function. Although it was not possible to
      identify putative donor taxa for all acquired genes, it was clear that genes were
      acquired from a wide range of Bacteria, including Spirochaetes, Firmicutes,
      Actinobacteria, mycoplasmas and several subdivisions of the Proteobacteria. We
      did not observe HGT from Archaea to the epsilon-Proteobacteria. The majority of
      acquired genes were operational genes involved in transport, metabolism, signal
      transduction and energy production and conversion.

PMID- 15950130
TI  - Biocontrol of Bacillus subtilis against Fusarium verticillioides in vitro and at
      the maize root level.
AB  - Bacillus species as a group offer several advantages over other bacteria for
      protection against root pathogens because of their ability to form endospores,
      and because of the broad-spectrum activity of their antibiotics. The objectives
      of this work were to determine the ability of strains of Bacillus to inhibit
      Fusarium verticillioides growth and fumonisin B(1) accumulation in vitro, and to
      evaluate the ability of the best bacterium for preventing rhizosphere and
      endorhizosphere colonization by F. verticillioides. Bacterial populations from
      the maize rhizoplane were obtained, and the capacity of ten Bacillus strains to
      inhibit fungal growth and fumonisin B(1) accumulation in vitro was assayed.
      According to these results, B. subtilis CE1 was selected as the best antagonist
      for testing maize root colonization of F. verticillioides. Bacillus subtilis CE1
      at 10(8) and 10(7) CFU ml(-1) inocula was able to reduce rhizoplane and
      endorhizosphere colonization of F. verticillioides in greenhouse trials. The
      strain B. subtilis CE1 could be a potential biological control agent against F.
      verticillioides at the root level.

PMID- 15950131
TI  - Grouping of streptomycetes using 16S-ITS RFLP fingerprinting.
AB  - A total of 463 Streptomyces and Kitasatospora type strains were screened using
      16S-ITS RFLP fingerprinting (combined restriction digest using enzymes BstUI and
      HaeIII). In total, 59 clusters could be delineated, each comprising multiple
      strains with nearly identical patterns. Good correlation was found in general
      with phylogeny, as revealed by 16S rDNA sequencing. Most strains assigned to a
      particular 16S-ITS RFLP cluster were classified into the corresponding 16S
      sequencing cluster whether a 16S similarity cut-off value of 97 or 98% was used.
      We conclude that the taxonomic resolution of 16S-ITS RFLP fingerprinting is
      higher than that of 16S rDNA sequencing; this may provide a tool for reducing the
      number of laborious DNA-DNA hybridizations necessary for discovering potentially
      new species within Streptomyces.

PMID- 15950132
TI  - Molecular phylogeny of the genus Pseudomonas based on rpoB sequences and
      application for the identification of isolates.
AB  - Phylogenetic relationships within the genus Pseudomonas were examined by
      comparing partial (about 1000 nucleotides) rpoB gene sequences. A total of 186
      strains belonging to 75 species of Pseudomonas sensu stricto and related species
      were studied. The phylogenetic resolution of the rpoB tree was approximately
      three times higher than that of the rrs tree. Ribogroups published earlier
      correlated well with rpoB sequence clusters. The rpoB sequence database generated
      by this study was used for identification. A total of 89 isolates (79.5%) were
      identified to a named species, while 16 isolates (14.3%) corresponded to unnamed
      species, and 7 isolates (6.2%) had uncertain affiliation. rpoB sequencing is now
      being used for routine identification of Pseudomonas isolates in our laboratory.

PMID- 15950133
TI  - Dyspnea and leg effort during exercise.
AB  - Dyspnea and leg effort are the major symptoms limiting exercise in healthy
      subjects and in patients with a variety of respiratory disorders. Quantitative
      measurement of both symptoms may be obtained by category scales such as VAS and
      Borg, with the latter being widely used. Furthermore, descriptor clusters of
      dyspnea help to assess some of the reasons for stopping exercise. The intensity
      of dyspnea and leg effort are similar in different disease states; this symmetry
      suggests that the limiting discomfort is a function of the intensity of increased
      motor drive to peripheral and respiratory muscles. An alternative explanation for
      the factors which limit exercise is that the subjects stop exercise volitionally
      when the discomfort associated with continuing exercise exceeds that which they
      are willing to tolerate. Muscle strength contributes to the intensity of dyspnea
      and leg effort at a given power output: the greater the muscle force, the lower
      the symptom. Symptoms also correlate with intensity and duration of a task by a
      power function in such a way that when minimizing the intensity of a given
      muscular task by prolonging the duration of activity, the symptom is drastically
      reduced. Skeletal muscle fatigue may be a factor limiting exercise tolerance both
      in healthy subjects and in patients with cardiorespiratory disorders. In
      conclusion, symptom measurement complements physiological measurements, both
      being essential to a comprehensive understanding of exercise tolerance.

PMID- 15950134
TI  - Extrinsic allergic alveolitis caused by misting fountains.
AB  - Recently, an increasing number of patients were presented to our clinics with
      febrile and respiratory symptoms associated with exposure to a new type of
      domestic ultrasonic humidifier. We report on 11 patients who developed recurrent
      episodes of fever, cough and dyspnea after repeated exposure to ultrasonic
      misting fountains at home. A diagnosis of extrinsic allergic alveolitis (EAA) or
      toxic alveolitis was made on the basis of the history and the clinical,
      radiological, laboratory and immunological findings. Eight patients were
      subjected to inhalative challenge tests with their own ultrasonic misting
      fountains, and all of them exhibited positive reactions. Nine patients were
      diagnosed with an EAA (humidifier lung) and two patients with a toxic alveolitis
      (humidifier fever). This study demonstrates the potential for ultrasonic misting
      fountains to cause illness in the home. In view of the increasing popularity of
      these devices, humidifier lung and humidifier fever should be considered in the
      differential diagnosis of patients with unexplained pulmonary or flu-like
      illnesses with fever.

PMID- 15950135
TI  - Concomitant upper-lobe bullous emphysema, lower-lobe interstitial fibrosis and
      pulmonary hypertension in heavy smokers: report of eight cases and review of the
      literature.
AB  - INTRODUCTION: Smoking can cause a variety of pulmonary interstitial diseases.
      Pulmonary fibrosis has traditionally been considered a non-smoking-related
      disease. Recently, however, evidence of smoking-induced fibrosis has emerged.
      SUBJECTS AND METHODS: A group of eight patients from the pulmonary clinic in
      Rabin Medical Center with a combine presentation of fibrosis and emphysema was
      identified retrospectively. All patients underwent chest computed tomography and
      pulmonary function tests. One patient underwent lung-heart transplantation and a
      complete review of his lung pathology was obtained. Transbronchial biopsy was
      performed in 3 additional patients and echocardiography was performed to evaluate
      the pulmonary vasculature. RESULTS: Upper-lobe emphysema with bulluos changes was
      found in all patients. In addition, a basal interstitial process was recognized,
      ranging from ground glass opacities to severe pulmonary fibrosis, with
      honeycombing. The radiological findings matched the pathological results of
      combined emphysema and usual interstitial pneumonia. Pulmonary function tests
      were also in accord, showing severe hypoxemia with mild obstruction, normal-to
      mildly reduced lung volumes and a severe decrease in diffusion capacity. Most of
      the patients had moderate-to-severe pulmonary hypertension as well as diffuse
      coronary artery disease. CONCLUSION: Our findings are in line with emerging
      evidence that the spectrum of interstitial damage caused by smoke includes not
      only Langerhans cell hystiocytosis, respiratory bronchiolitis or desquamative
      interstitial pneumonia but also advanced usual interstitial pneumonitis as well.
      We believe that in some patients smoking plays a destructive role by a variety of
      mechanisms and can cause emphysema, lung fibrosis as well as pulmonary
      vasculopathy and hypertension. Future studies are needed to define the genetics
      and pathophysiology of this uncommonly reported clinical syndrome.

PMID- 15950136
TI  - Variables associated with recovery from acute exacerbations of chronic bronchitis
      and chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To identify risk factors for late recovery and failure after
      ambulatory treatment of exacerbations of chronic bronchitis (CB) and chronic
      obstructive pulmonary disease (COPD). METHODS: Observational, non-randomised
      study of risk factors carried out in 2001 and 2002 in Primary Care practices.
      Patients aged 40 or older diagnosed with an exacerbation of CB or COPD of
      probable bacterial etiology were included in the study and followed up for 10
      days. Patients were treated with amoxicillin plus clavulanic acid (co-amoxiclav)
      500-125 mg tds for 10 days, clarithromycin 500 mg bd for 10 days or moxifloxacin
      400 mg od for 5 days. RESULTS: Two hundred and fifty-two general practitioners
      participated, registering 1147 valid patients. The rate of failure at day 10 was
      15.1% without significant differences among the antibiotic treatments. Median
      time to recovery was 5 days. Factors significantly associated with late recovery
      (>5 days) on multivariate analysis were: use of long-term oxygen (OR=1.96;
      95%CI=1.35-2.85); use of short-acting beta-2 agonists (OR=1.51; 1.17-1.92). The
      use of moxifloxacin had a "protective" effect against late recovery compared to
      co-amoxiclav (OR=0.34; 0.26-0.45) and clarithromycin (OR=0.41; 0.31-2.85).
      Factors associated with therapeutic failure were: previous hospitalisation
      (OR=1.61; 1.08-2.42); and 2 or more exacerbations the previous year (OR=1.51;
      1.04-2.17); criteria of CB had a protective effect against failure (OR=0.53; 0.35
      0.79). CONCLUSIONS: There are readily identifiable risk factors for ambulatory
      treatment failure of exacerbations of CB and COPD. In addition, long-term oxygen
      therapy and short-acting beta-2 agonists are associated with late recovery, and
      the use of moxifloxacin compared with co-amoxiclav and clarithromycin is
      associated with faster recovery of symptoms.

PMID- 15950137
TI  - Community-acquired pneumonia by Legionella pneumophila serogroups 1-6 in Brazil.
AB  - A prospective cohort study of adult patients hospitalized due to community
      acquired pneumonia was carried out for 1 year in a Brazilian university general
      hospital to detect the incidence of community-acquired pneumonia by Legionella
      pneumophila serogroups 1-6. During a whole year, a total of 645 consecutive
      patients who were hospitalized due to a initial presumptive diagnosis of
      respiratory disease by ICD-10 (J00-J99), excluding upper respiratory diseases,
      were screened to detect the patients with community-acquired pneumonia. Fifty
      nine consecutive patients hospitalized due to community-acquired pneumonia
      between July 19, 2000 and July 18, 2001, were included in the study. They had
      determinations of serum antibodies to L. pneumophila serogroups 1-6 by indirect
      immunofluorescence antibody test at the Infectious Diseases Laboratory of
      University of Louisville (KY, USA) and urinary antigen tests for L. pneumophila
      serogroup 1. Three patients had community-acquired pneumonia by L. pneumophila
      serogroups 1-6, two patients being diagnosed by seroconversion and positive
      urinary antigen tests; the other had negative serologies but strongly positive
      urinary antigen test. The incidence of community-acquired pneumonia by L.
      pneumophila serogroups 1-6 in our hospital was 5.1%.

PMID- 15950138
TI  - Long-term reduction of hyperinflation in stable COPD by non-invasive nocturnal
      home ventilation.
AB  - OBJECTIVE: The role of non-invasive positive pressure ventilation (NPPV) in
      stable COPD with chronic ventilatory failure remains controversial. The impact of
      long-term home nocturnal NPPV treatment on deflation has not yet been evaluated
      in detail. METHODS: Retrospective explorative study of 46 patients with stable
      COPD undergoing NPPV treatment. Effects of NPPV on body plethysmographic
      parameters, blood gas tensions and inspiratory muscle function after 6.2 (+/-1.7)
      and 12.7 (+/-2.1) months of treatment. Further, evaluation of 1-year survival,
      compliance and ventilation parameters. RESULTS: One-year survival was 89.1%. The
      effectiveness of ventilation was proven by a significant reduction in nocturnal
      and daytime PaCO2. We observed a decrease in the ratio of residual volume (RV) to
      total lung capacity (TLC) on the average of 5.2+/-9.8% (or 15.2+/-29.7% pred.;
      P<0.01) at six and 3.9+/-9.0% (or 12.9+/-18.6% pred.; P<0.001) at 12 months. As a
      consequence, we found significant improvements in inspiratory capacity (IC),
      vital capacity (VC) and forced expiratory volume in one second (FEV1). For
      patients with the most severe hyperinflation (RV/TLC>75%), we found a significant
      positive correlation between inspiratory positive airway pressure (IPAP) and
      reductions in PaCO2 (r=0.56; P<0.05) and RV/TLC (r=0.50; P<0.05). CONCLUSIONS: In
      severe hypercapnic stable COPD long-term nocturnal NPPV can reduce hyperinflation
      with sustained improved daytime blood gas parameters.

PMID- 15950139
TI  - Characteristics of a population of COPD patients identified from a population
      based study. Focus on previous diagnosis and never smokers.
AB  - OBJECTIVE: To identify factors associated with diagnosis and health-related
      quality of life (HRQL) impairment in chronic obstructive pulmonary disease (COPD)
      patients from a population-based epidemiological study. DESIGN AND PARTICIPANTS:
      This was an epidemiologic, multicenter, population-based study. Three hundred and
      sixty-three individuals diagnosed with COPD from a randomly general population
      sample of 4035 individuals aged 40-69 were included in the analyses.
      INTERVENTIONS: Forced spirometry was performed on eligible subjects, and the
      European Commission for Steel and Coal (ECSC) and the St. George's Respiratory
      Questionnaires (SGRQ) were completed. Logistic regression models were constructed
      to identify variables associated with the previous diagnosis of COPD and with
      COPD in never smokers. A multiple linear regression model attempted to identify
      variables influencing HRQL impairment. RESULTS: Only 79 (21.7%) COPD patients had
      been previously diagnosed. Disease severity based on FEV(1), worse SGRQ score,
      previous respiratory disease, as well as the presence of wheezing were
      significantly associated with previous diagnosis. Being a woman, older than 55,
      with previous respiratory disease and without expectoration or wheezing
      characterized COPD in never smokers. A worse HRQL was associated with chronic
      symptoms, especially dyspnea; and with older age, cardiac comorbidity and
      impairment in lung function. CONCLUSIONS: Diagnosis of COPD in the community is
      more likely in patients with worse lung function and HRQL, and wheezing is the
      symptom most strongly associated with a diagnosis of COPD. Women older than 55,
      with previous respiratory diseases, without respiratory symptoms and mild airflow
      obstruction constitute the majority of individuals with COPD who have never
      smoked. Chronic respiratory symptoms are strongly associated with impairment in
      HRQL.

PMID- 15950141
TI  - Body composition by bioelectrical impedance predicts mortality in chronic
      obstructive pulmonary disease patients.
AB  - Pulmonary rehabilitation is recommended in international treatment guidelines for
      chronic obstructive pulmonary disease (COPD). No one has however studied the
      effect on long-term mortality. The aim of the current study was to study the
      mortality in a sample of patients with severe COPD included in a 1-year
      multidisciplinary rehabilitation program. Body composition was assessed at
      baseline using bioelectrical impedance. Mortality was studied in 86 patients
      using the Cox proportional hazards model. Forty-seven (55%) of the patients died
      during the mean follow-up time which was almost 6 years. Risk of mortality
      increased with increasing age, increasing number of hospital days the year before
      inclusion and men had higher mortality risk than women. The mortality risk
      decreased with increasing % reference body weight, increasing fat-free mass index
      (FFMI), increasing FEV(1) and increasing 6-min walking distance. Gender, age and
      FFMI continued to be statistical significant predictors of mortality when
      controlling for the other baseline variables in a multivariate analysis. To
      conclude, body composition, measured by bioelectrical impedance and presented as
      FFMI, is an independent predictor of mortality in COPD patients.

PMID- 15950140
TI  - Light smoking and dependence symptoms in high-school students.
AB  - In high-school students, prevalence of smoking is high but few studies analyzed
      smoking in the student population according to nicotine content of smoked
      cigarettes and gender. We analyzed the responses to a questionnaire, including
      the modified Fagerstrom Tolerance Questionnaire (FTQ), administered to 555
      students (382 males, 173 females) of a professional high school in Palermo,
      Italy, to assess the prevalence in both genders of: (1) smoking "light" and high
      nicotine (HN) cigarettes; (2) signs of nicotine dependence and (3) respiratory
      symptoms. Nicotine content of habitually smoked cigarettes was considered as
      "light" if 0.8 mg; as high if >0.8 mg. Forty-four percent of students smoked,
      without differences between genders. Two-thirds of the total sample reported
      "light" cigarette smoking (76.7% of females vs. 62.0% of males, P<0.05). On
      average, "light" cigarette smoking was associated with lower pack/year and FTQ
      global score compared to HN smoking. However, when FTQ global score was analyzed
      by taking into account pack/year, no major difference was found between "light"
      and HN cigarette smokers. Cough with phlegm and breathlessness were more
      frequently reported by smoking than non-smoking students, without differences
      between "light" and HN cigarette smokers. About 50% of smoking students reported
      having tried to quit, while only 3.4% of students were ex-smokers. "Light"
      smoking was common in high school students, especially among females. Dependence
      appeared more influenced by the smoking history than by nicotine content.
      Respiratory symptoms were similar in "light" and HN cigarette smokers.

PMID- 15950142
TI  - Body mass index, asthma and allergic rhinoconjunctivitis in Swedish conscripts-a
      national cohort study over three decades.
AB  - Obesity and overweight have been associated with an increased risk of asthma in
      children as well as adults. The association between atopy and body mass index
      (BMI) is less clear. It has also been suggested that the link between a high BMI
      and asthma could be a recent phenomenon. The objective of this study was to
      assess whether the association with BMI differed between allergic
      rhinoconjunctivitis and asthma and if these associations have changed over time.
      The Swedish Military Service Conscription Register was linked to the Register of
      the Total Population and the Population and Housing Censuses. Asthma (with and
      without allergic rhinoconjunctivitis) and allergic rhinoconjunctivitis at
      conscription were analysed in relation to BMI for 1,247,038 male conscripts in
      successive cohorts born between 1952 and 1977. Obesity was associated with asthma
      without allergic rhinoconjunctivitis, adjusted OR 1.53 (95% CI 1.43-1.63), and
      with asthma with allergic rhinoconjunctivitis, adjusted OR 1.34 (95% CI 1.20
      1.50), but not with allergic rhinoconjunctivitis, OR 1.00 (95% CI 0.97-1.03)
      after multivariate analyses with adjustments for confounders. The odds ratios
      were similar in three successive cohorts (conscripts born in 1952-1961, 1962-1971
      and 1972-1977). Underweight was associated with a slightly increased risk for all
      three conditions. The increased risk of asthma in young Swedish men with obesity
      has remained unchanged over a period of three decades.

PMID- 15950143
TI  - Exhaled nitric oxide levels in school children in relation to IgE sensitisation
      and window pane condensation.
AB  - BACKGROUND: A positive relation between exhaled nitric oxide (NO) levels and
      allergen exposure has been found in some studies whereas there is less
      information on how non-allergen environmental factors influences exhaled NO.
      OBJECTIVE: To study the relationship between exhaled NO levels in schoolchildren
      in relation to IgE sensitisation and allergenic and non-allergenic environmental
      factors. METHOD: This study comprised 374 schoolchildren (13-14 years of age) who
      performed exhaled NO-measurements and skin prick tests. Exposure to allergens,
      respiratory infections, environmental tobacco smoke and home window pane
      condensation, the latter an indicator of high humidity and poor ventilation was
      evaluated through questionnaires. RESULTS: In IgE-sensitised children
      sensitisation to pets was a more important determinant of exhaled NO than
      sensitisation to pollen. Higher NO levels were found in cat-sensitised children
      with a cat or other furred pets at home compared to cat-sensitised children
      without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher
      exhaled NO levels were found in non-sensitised children that reported having a
      cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation
      (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and
      window pane condensation, respectively. These associations were not found in
      children that were sensitised to inhalation allergens. CONCLUSION: Allergen
      exposure seems to be the most important determinant for exhaled NO levels in IgE
      sensitised children whereas in non-sensitised children NO levels were associated
      with respiratory infections and home window pane condensation.

PMID- 15950144
TI  - Sick leave in patients with obstructive lung disease is related to psychosocial
      and work variables rather than to FEV1.
AB  - The aim of this exploratory study was to investigate associations between sick
      leave in workers with asthma or COPD and disease-related variables, psychosocial
      variables, and work characteristics. Hundred and eighty-nine patients with
      physician-diagnosed asthma (N=118) or COPD (n=71) who had paid work in the past
      12 months completed questionnaires on sick leave, health complaints, functional
      limitations, work characteristics and psychosocial issues, and underwent a
      pulmonary function test (FEV1 and FVC before and after bronchodilation). Logistic
      regression analyses were performed to investigate variables independently
      associated with high sick leave (i.e. more than twice a year and/or longer than 1
      month per episode). Asthma patients, not having an emotionally difficult job,
      with low job satisfaction, who had changed employers, utilized job control, and
      who encountered pulmonary aggravating factors at work were found to have a higher
      incidence of sick leave. COPD patients, who had informed the employer or
      colleagues about the disease, who did not have difficult tasks at work, who did
      not hide dyspnea and limitations, and who reported high fatigue were showing
      higher sick leave. FEV1 and FVC were not associated with sick leave in either
      group. It was concluded that psychosocial variables, work characteristics,
      functional limitations, and complaints play a more important role in sick leave
      in workers with asthma and COPD than FEV1.

PMID- 15950145
TI  - Evaluation of the relationship between cockroach sensitivity and house-dust-mite
      sensitivity in Turkish asthmatic patients.
AB  - Exposure to cockroach has been identified as an important source of indoor
      allergens in patients with asthma and allergic rhinitis. We evaluated the
      relationship between cockroach sensitivity and other allergens in patients with
      asthma. A total of 114 patients, defined asthma according to GINA, were enrolled
      in this study. A questionnaire including age, sex, duration of asthma, history of
      cockroach presence at home, and total IgE, blood eosinophil count, pulmonary
      function tests, standard skin prick test additional cockroach and shrimp allergen
      were performed. There were 84 (73.7%) female and 30 (26.3%) male patients with a
      mean age of 38.1+10.1 years. The average duration of asthma was 7.7+7.2 years.
      Sixty five (57%) patients were determined atopic and 49 (43%) nonatopic. Pollen
      allergen was the most common allergen in 59 (51.8%) patients with asthma, and
      second common allergen was mite allergen in 43 (37.7%) patients. Cockroach
      sensitivity were detected in 23 (20.2%) of 114 all asthmatics and 23 (35%) of
      atopic asthmatics. High rates of house-dust-mite allergy (73.9%) was determined
      in patients with cockroach sensitivity (P<0.05), while we found no relationship
      with other allergens. There was no difference for cockroach sensitivity between
      rural and urban population. Cockroach sensitivity was more common in mild
      bronchial asthmatics and a female predominance was observed. In addition, there
      was no association between shrimp and cockroach sensitivity. As a result, a high
      rate of cockroach sensitivity alone or with mite sensitivity was seen in patients
      with bronchial asthma in Turkish population. Because of cross-reactivity between
      mites and cockroach, cockroach sensitivity should be investigated in patients
      with house-dust-mite allergy. In addition, a high rate of cockroach sensitivity,
      in terms of IgE sensitization, may be important for the development of new
      sensitizations.

PMID- 15950146
TI  - Does pleural tuberculosis disease pattern differ among developed and developing
      countries.
AB  - BACKGROUND: A number of reports from developed countries have documented a rising
      age at which pleural tuberculosis occurs and increase in the frequency of
      reactivation disease being as the main cause of pleural involvement. OBJECTIVE:
      To determine the age at which pleural tuberculosis occurs, study its clinical
      pattern, and to determine whether pleural tuberculosis is a result of
      reactivation of pulmonary tuberculosis or it is a primary one comparing our
      findings with results from developed countries. METHOD: Retrospective study of
      100 cases discharged from Hamad General Hospital with the diagnosis of pleural
      tuberculosis from January 1996 to December 2002. RESULTS: Pleural tuberculosis
      tends to affect younger age groups (84% are below the age of 45 years, with mean
      age of 31.5). The disease tends to be mostly a primary infection. Fever is the
      most common symptom (90%) and the disease is usually an acute or sub acute one.
      Weight loss precedes other symptoms. Exudative pleural effusion with predominant
      lymphocytosis is characteristic. Majority of patients have no predisposing
      conditions for the disease. CONCLUSION: In contrast to what has been reported in
      some developed countries, Pleural tuberculosis tends to be a primary disease in
      the present study. Younger age groups are particularly affected.

PMID- 15950147
TI  - Bronchial challenge, assessed with forced expiratory manoeuvres and airway
      impedance.
AB  - OBJECTIVE: The Methacholine concentration at which a 20% decrease of the forced
      expiratory volume in 1s (PC20_FEV1) or a 40% increase in airway resistance
      (PC40_Rrs6) occur are accepted indicators for airway hyperresponsiveness. We
      hypothesised that the level of detection of bronchial hyperresponsiveness will
      differ between the two methods. METHODS: The response to Methacholine was
      assessed by forced oscillation technique (FOT) and spirometry in 20 stable
      hyperresponsive asthmatics. The effects of repeated lung function measurements on
      respiratory muscle fatigue were measured from maximal inspiratory mouth pressure
      (MIP). After each dose, patients scored their perception of dyspnoea on a BORG
      scale. Differences in patient's burden were measured by comparing the BORG-score
      at PC40_Rrs6 (BORG-PC40_Rrs6) and at PC20_FEV1 (BORG-PC20_FEV1). Reproducibility
      was also evaluated. RESULTS: The PC20_FEV1-values were 2.2 (0.4) doubling dose
      higher as compared to the PC40_Rrs6 (P<0.001). The mean BORG-score at PC40_Rrs6
      was 1.7 points lower as compared to the BORG-score at PC20_FEV1 (P<0.001). The
      difference (mean(sd)) between the PC20_FEV1 of measurement 1 and 2 was -0.1 (1.4)
      doubling dose, and -0.3 (2.7) doubling dose for PC40_Rrs6. The MIP after
      Methacholine provocation was 1.0(0.2) kPa lower as compared to the MIP before the
      challenge test (P<0.001), suggesting respiratory muscle fatigue. CONCLUSION:
      Measuring PC40_Rrs6 shortens the challenge test and lowers the concentrations of
      bronchoconstrictor agents as compared to measurements of PC20_FEV1. The FOT
      method was less strenuous for patients. In spite of the fact that the
      reproducibility is two-fold worse than measuring PC20_FEV1, it still remains
      quite acceptable at a mean of 0.3 doubling dose. The respiratory muscle strength
      was deteriorated after the challenge test.

PMID- 15950148
TI  - Evolution of changes in carbon monoxide transfer factor in men with chronic
      obstructive pulmonary disease.
AB  - Progression of chronic obstructive pulmonary disease (COPD) has been studied
      predominantly by following change in forced expiratory volume in 1s (FEV1) which
      reflects both primary airway disease and associated alveolar disease. Carbon
      monoxide transfer (Tlco) (the product of the transfer coefficient Kco and
      alveolar volume Va) is the only simple, widely available test of alveolar
      function, but few studies have followed long-term changes in an individual.
      Seventeen middle-aged men with moderate chronic airflow obstruction (mean FEV1
      56% of predicted values) were observed with yearly measurements of FEV1, Tlco and
      Kco over a mean of 18.9 yr. At the end of follow-up FEV1 had fallen to 29% of
      predicted values. Va, measured by single breath dilution, fell in each man. Kco
      at recruitment ranged from 41% to 110% predicted and remained >75% predicted in
      eight men at the end of follow-up supporting a phenotype of COPD with predominant
      airway disease and little emphysema. Fall in FEV1 was faster (2.03% predicted
      FEV1/yr) in seven men with low initial Kco<75% pred. than in men with initial
      Kco>75% pred. (1.14% predicted FEV1/yr, P=0.006). Repeated measurements of CO
      transfer in an individual should increase the present poor knowledge of the
      contribution of alveolar disease to the progression of chronic airflow
      obstruction.

PMID- 15950149
TI  - Effect of body position on gas exchange after bronchoalveolar lavage.
AB  - OBJECTIVE: To assess the possible influence of body position on oxygen saturation
      after bronchoscopy (BC) with bronchoalveolar lavage (BAL). DESIGN: Prospective,
      open, randomized study. SETTING: The respiratory unit of a first level, community
      hospital. PATIENTS: Forty-one consecutive patients in which BC with BAL, using at
      least 150 mL of BAL fluid, was performed. METHOD: We randomly assigned 21
      patients to lie in lateral decubitus (LD) with the lung where BAL was performed
      uppermost after BC, and 20 to lie in supine position (SP). Oxygen saturation
      (SO2) was measured for all patients from 10 min before to 30 min after the end of
      the BC. Saturation parameters were compared for both groups. RESULTS: Mean SO2
      was significantly lower after than before the BC, both for LD and SP groups (LD:
      91.4+/-3% vs. 94.9+/-2%, respectively; P=0.0001) (SP: 91.6+/-3 vs. 95.8+/-3%,
      respectively; P=0.0003). We did not find significant differences between LD and
      SP groups, after BC, regarding mean SO2 (91.4+/-3% vs. 91.6+/-3%), minimum SO2
      (86.2+/-4.5% vs. 86.6+/-5.4%, respectively) or percentages of registry time at
      saturations below 90% (26.3+/-35.9% vs. 27.6+/-38.2%, respectively) (P:NS for all
      values). CONCLUSION: BC with BAL caused significant oxygen desaturation in our
      patients. We have not been able to demonstrate a significant influence of body
      position on SO2 after BAL.

PMID- 15950150
TI  - High justification for universal stringent precautions in lung function testing.

PMID- 15950152
TI  - PDTC and NO suppress CC chemokine production in TNF-alpha-stimulated human
      pulmonary microvascular endothelial cells.

PMID- 15950153
TI  - ATF5 regulates the proliferation and differentiation of oligodendrocytes.
AB  - The transcription factor ATF5 is expressed in cells of the embryonic and neonatal
      ventricular zone/subventricular zone (VZ/SVZ), and must be down-regulated for
      their differentiation into neurons and astrocytes. Here, we show that ATF5 plays
      a major role in directing oligodendrocyte development. ATF5 is expressed by
      oligodendrocyte precursors but is absent from mature oligodendroglia.
      Constitutively expressed ATF5 maintains SVZ cells and O4(+) oligodendrocyte
      precursors in cycle and inhibits their differentiation into oligodendrocytes in
      vitro and in vivo. In contrast, ATF5 loss-of-function (LOF; produced by a
      dominant-negative form of the protein) accelerates oligodendrocyte
      differentiation of O4(+) cells in vitro and of SVZ cells in vivo. Significantly,
      the accelerated oligodendrocyte differentiation promoted by ATF5 LOF in vivo
      results in aberrant migration. Thus, appropriately regulated expression of ATF5
      is required for proper expansion of oligodendroglial progenitors as well as for
      their timely differentiation. Regulation of oligodendrocyte, astrocyte, and
      neuronal differentiation indicates that ATF5 operates as a general regulator of
      the timing of differentiation, independent of cell lineage.

PMID- 15950154
TI  - Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain.
AB  - We have examined the influence of thyroid hormone on adult hippocampal
      neurogenesis, which encompasses the proliferation, survival and differentiation
      of dentate granule cell progenitors. Using bromodeoxyuridine (BrdU), we
      demonstrate that adult-onset hypothyroidism significantly decreases hippocampal
      neurogenesis. This decline is predominantly the consequence of a significant
      decrease in the survival and neuronal differentiation of BrdU-positive cells.
      Both the decreased survival and neuronal differentiation of hippocampal
      progenitors could be rescued by restored euthyroid status. Adult-onset
      hyperthyroidism did not influence hippocampal neurogenesis, suggesting that the
      effects of thyroid hormone may be optimally permissive at euthyroid levels. Our
      in vivo and in vitro results revealed that adult hippocampal progenitors express
      thyroid receptor isoforms. The in vitro studies demonstrate that adult
      hippocampal progenitors exhibit enhanced proliferation, survival and glial
      differentiation in response to thyroid hormone. These results support a role for
      thyroid hormone in the regulation of adult hippocampal neurogenesis and raise the
      possibility that altered neurogenesis may contribute to the cognitive and
      behavioral deficits associated with adult-onset hypothyroidism.

PMID- 15950155
TI  - Angiotensin-(1-7) enhances LTP in the hippocampus through the G-protein-coupled
      receptor Mas.
AB  - The renin-angiotensin system not only plays a critical role in blood pressure
      control but is also involved in learning and memory mechanisms. In addition to
      angiotensin (Ang) II, Ang-(1-7) may also have important biological activities in
      the brain. Here, we show for the first time that Ang-(1-7) enhances long-term
      potentiation (LTP) in the CA1 region of the hippocampus. Our studies with AT1
      receptor antagonists and selective Ang-(1-7) receptor antagonists demonstrate the
      existence of a distinct Ang-(1-7) receptor in the brain, the G-protein-coupled
      receptor Mas, encoded by the Mas protooncogene. We also show that the genetic
      deletion of this receptor abolishes the Ang-(1-7)-induced enhancement of LTP.
      Thus, we firstly demonstrate that Ang-(1-7) influences the induction of LTP in
      limbic structures implicating its distinct function in learning and memory
      mechanisms; secondly, we have identified Mas as a functional receptor for Ang-(1
      7) in the brain.

PMID- 15950156
TI  - Isolation and characterization of the Aspergillus nidulans eglC gene encoding a
      putative beta-1,3-endoglucanase.
AB  - The Aspergillus nidulans eglC gene, which encodes a putative beta-1,3
      endoglucanase, was isolated from a chromosome-specific library by using an
      expressed sequence tag, esd0113. The EglC open reading frame encodes a 465 amino
      acid polypeptide, of which the amino acid sequence showed 46% similarity to that
      of Saccharomyces cerevisiae beta-1,3-endoglucanase. The eglC transcript level at
      the early stages of asexual and sexual developments was dependent on the presence
      of the nsdD gene that encodes a GATA-type transcription factor, confirming that
      the nsdD gene is necessary for full accumulation of the eglC transcript. Deletion
      of the eglC gene did not affect the radial growth rate, the germination rate of
      conidia, and both of asexual and sexual development. However, deletion of the
      gene led to hyphae more resistant to a cell wall-lyzing enzyme, implying that the
      cell wall structure of the eglC-null mutant is altered from a wild type one.
      Furthermore, deletion of the fadA and sfaD genes, that encode a Galpha and a
      Gbeta subunits of a heterotrimeric G protein, respectively, did not affect the
      eglC transcript level at the early developmental stages. In contrast, deletion of
      the flbA gene, that codes for a regulatory protein having an RGS (regulator of G
      protein signaling) motif, led to decrease in the eglC transcript level. The eglC
      transcript level was not higher in a creA mutant than in a wild type, indicating
      that the eglC gene is not sensitive to carbon-catabolite repression.

PMID- 15950157
TI  - Molecular and functional characterization of a fructose specific transporter from
      the gray mold fungus Botrytis cinerea.
AB  - In the gray mold fungus Botrytis cinerea, spore germination and plant infection
      are stimulated in the presence of nutrients, in particular sugars. Applied at
      micromolar concentrations, fructose is a more potent inducer of germination than
      glucose. To test whether preferred fructose uptake is responsible for this
      effect, and to study the mechanism of fructose transport in B. cinerea, a gene
      (frt1) encoding a fructose transporter was cloned. FRT1 is highly similar to
      recently identified fructose transporters of yeasts, but much less to other
      fungal hexose transporters characterized so far. By using a hexose uptake
      deficient yeast strain for expression, FRT1 was found to be a high affinity
      proton coupled symporter specific for fructose but not for glucose. B. cinerea
      frt1 disruption mutants were created and showed normal vegetative growth and
      plant infection, but a delay in fructose-induced germination when compared to
      wild-type. Sugar uptake experiments with both wild-type and mutant conidia showed
      a higher affinity for glucose than for fructose. Thus, we propose that the
      specific effect of fructose on germination is not due to transport but rather to
      an as yet unknown intracellular sensing.

PMID- 15950158
TI  - Gene identification in the oomycete pathogen Phytophthora parasitica during in
      vitro vegetative growth through expressed sequence tags.
AB  - Phytophthora parasitica is a soilborne oomycete pathogen capable of infecting a
      wide range of plants, including many solanaceous plants. In a first step towards
      large-scale gene discovery, we generated expressed sequence tags (ESTs) from a
      cDNA library constructed using mycelium grown in synthetic medium. A total of
      3568 ESTs were assembled into 2269 contiguous sequences. Functional
      categorization could be performed for 65.45% of ESTs. A significant portion of
      the transcripts encodes proteins of common metabolic pathways. The most prominent
      sequences correspond to members of the elicitin family, and enzymes involved in
      the lipid metabolism. A number of genes potentially involved in pathogenesis were
      also identified, which may constitute virulence determinants.

PMID- 15950159
TI  - [Structures of the lac operon proteins].

PMID- 15950160
TI  - The lac repressor.
AB  - Few proteins have had such a strong impact on a field as the lac repressor has
      had in Molecular Biology. Over 40 years ago, Jacob and Monod [Genetic regulatory
      mechanisms in the synthesis of proteins, J. Mol. Biol. 3 (1961) 318] proposed a
      model for gene regulation, which survives essentially unchanged in contemporary
      textbooks. It is a cogent depiction of how a set of 'structural' genes may be
      coordinately transcribed in response to environmental conditions and regulates
      metabolic events in the cell. In bacteria, the genes required for lactose
      utilization are negatively regulated when a repressor molecule binds to an
      upstream cis activated operator. The repressor and its operator together form a
      genetic switch, the lac operon. The switch functions when inducer molecules alter
      the conformation of the repressor in a specific manner. In the presence of a
      particular metabolite, the repressor undergoes a conformational change that
      reduces its affinity for the operator. The structures of the lac repressor and
      its complexes with operator DNA and effector molecules have provided a physical
      platform for visualizing at the molecular level the different conformations the
      repressor and the molecular basis for the switch. The structures of lac
      repressor, bound to its operator and inducer, have also been invaluable for
      interpreting a plethora of biochemical and genetic data.

PMID- 15950161
TI  - The structure of E. coli beta-galactosidase.
AB  - E. coli beta-galactosidase is a tetramer of four identical 1023-amino acid
      chains. Each chain consists of five domains, the third of which is an eight
      stranded alpha/beta barrel that comprises much of the active site. This site
      does, however, include elements from other domains and other subunits. The N
      terminal region of the polypeptide chains help form one of the subunit
      interfaces. Taken together these features provide a structural basis for the well
      known property of alpha-complementation. Catalytic activity proceeds via the
      formation of a covalent galactosyl intermediate with Glu537, and includes
      'shallow' and 'deep' modes of substrate binding.

PMID- 15950162
TI  - Structure and mechanism of the lactose permease.
AB  - More than 20% of the genes sequenced thus far appear to encode polytopic
      transmembrane proteins involved in a multitude of critical functions,
      particularly energy and signal transduction. Many are important with regard to
      human disease (e.g., depression, diabetes, drug resistance), and many drugs are
      targeted to membrane transport proteins (e.g., fluoxetine and omeprazole).
      However, the number of crystal structures of membrane proteins, especially ion
      coupled transporters, is very limited. Recently, an inward-facing conformer of
      the Escherichia coli lactose permease (LacY), a paradigm for the Major
      Facilitator Superfamily, which contains almost 4000 members, was solved at about
      3.5 A in collaboration with Jeff Abramson and So Iwata at Imperial College
      London. This intensively studied membrane transport protein is composed of two
      pseudo-symmetrical 6-helix bundles with a large internal cavity containing bound
      sugar and open to the cytoplasm only. Based on the structure and a large body of
      biochemical and biophysical evidence, a mechanism is proposed in which the
      binding site is alternatively accessible to either side of the membrane.

PMID- 15950163
TI  - The lac operon galactoside acetyltransferase.
AB  - Of the proteins encoded by the three structural genes of the lac operon, the
      galactoside acetyltransferase (thiogalactoside transacetylase, LacA, GAT) encoded
      by lacA is the only protein whose biological role remains in doubt. Here, we
      briefly note the classical literature that led to the identification and initial
      characterization of GAT, and focus on more recent results which have revealed its
      chemical mechanism of action and its membership in a large superfamily of
      structurally similar acyltransferases. The structural and sequence similarities
      of several members of this superfamily confirm the original claim for GAT as a
      CoA-dependent acetyltransferase specific for the 6-hydroxyl group of certain
      pyranosides, but do not yet point to the identity of the natural substrate(s) of
      the enzyme.

PMID- 15950164
TI  - RNA polymerase structure and function at lac operon.
AB  - Transcription of E. coli lac operon by RNA polymerase (RNAP) is a classic example
      of how the basic functions of this enzyme, specifically the ability to
      recognize/bind promoters, melt the DNA and initiate RNA synthesis, is positively
      regulated by transcription activators, such as cyclic AMP-receptor protein, CRP,
      and negatively regulated by lac-repressor, LacI. In this review, we discuss the
      recent progress in structural and biochemical studies of RNAP and its binary and
      ternary complexes with CRP and lac promoter. With structural information now
      available for RNAP and models of binary and ternary elongation complexes, the
      interaction between these factors and RNAP can be modeled, and possible molecular
      mechanisms of their action can be inferred.

PMID- 15950165
TI  - Malaria and asymptomatic parasitaemia in Gabonese infants under the age of 3
      months.
AB  - We determined the incidence of both malaria and asymptomatic parasitaemia in
      infants under the age of 3 months within the framework of a longitudinal cohort
      study in Lambarene, Gabon, between December 2002 and July 2004. Of 878 infants
      who were included at birth, we identified malaria in three infants and,
      additionally, asymptomatic parasitaemia in six infants. The malaria incidence
      density was 1.1/1000 person-months or 0.1% of observations. Our findings underpin
      the notion that the incidence of malaria and parasitaemia in infants below the
      age of 3 months is very low.

PMID- 15950166
TI  - Homogeneous fluorescent assay for RNA polymerase.
AB  - A new method for determination of RNA polymerase (RNAP) activity is presented.
      The method uses nucleoside tri- and tetraphosphate derivatives carrying 4
      methylumbelliferone residue at the terminal phosphate. Incorporation of such
      compounds in RNA by RNA polymerase is accompanied by release of di- and
      triphosphate derivatives of 4-methylumbelliferone. Subsequent treatment by
      alkaline phosphatase produces free 4-methylumbelliferone that is highly
      fluorescent and can be easily detected. The sensitivity of the method is higher
      than that reported in previous studies. The validity of the assay has been
      demonstrated by retrieving the RNAP inhibitors from a collection of 16,000
      compounds.

PMID- 15950167
TI  - Design of rocker switches for work-vehicles--an application of Kansei
      Engineering.
AB  - Rocker switches used in vehicles meet high demands partly due to the increased
      focus on customer satisfaction. Previous studies focused on ergonomics and
      usability rather than design for emotions and affection. The aim of this study
      was to determine how and to what extent engineering properties influence the
      perception of rocker switches. Secondary aims were to compare two types of rating
      scales and to determine consistency over time of the ratings. As a method Kansei
      Engineering was used, describing a product domain from a physical and semantic
      point of view. A model was built and validated, and recommendations for new
      designs were given. It was seen that the subjective impressions of robustness,
      precision and design are strongly influenced by the zero position, the contact
      position, the form-ratio, shape and the surface of rocker switches. A 7-point
      scale was found suitable. The Kansei ratings were consistent over time.

PMID- 15950168
TI  - Effect of computer mouse gain and visual demand on mouse clicking performance and
      muscle activation in a young and elderly group of experienced computer users.
AB  - The present study evaluated the specific effects of motor demand and visual
      demands on the ability to control motor output in terms of performance and muscle
      activation. Young and elderly subjects performed multidirectional pointing tasks
      with the computer mouse. Three levels of mouse gain and three levels of target
      size were used. All subjects demonstrated a reduced working speed and hit rate at
      the highest mouse gain (1:8) when the target size was small. The young group had
      an optimum at mouse gain 1:4. The elderly group was most sensitive to the
      combination of high mouse gain and small targets and thus, this age group should
      avoid this combination. Decreasing target sizes (i.e. increasing visual demand)
      reduced performance in both groups despite that motor demand was maintained
      constant. Therefore, it is recommended to avoid small screen objects and letters.
      Forearm muscle activity was only to a minor degree influenced by mouse gain (and
      target sizes) indicating that stability of the forearm/hand is of significance
      during computer mouse control. The study has implications for ergonomists,
      pointing device manufacturers and software developers.

PMID- 15950169
TI  - Contribution of the copper ions in the dinuclear active site to the stability of
      Carcinus aestuarii hemocyanin.
AB  - We have investigated the effect of copper binding on the structural properties of
      hemocyanin (Hc). To this aim, we have studied the holo- and apo-form of the
      protein, both in the hexameric and in the monomeric state (CaeSS2 subunit), with
      experimental approaches that report on the protein aggregation and conformational
      stability. The results of gel-filtration chromatography and small angle X-ray
      scattering (SAXS) provide evidence that the hydrodynamic and gyration radius
      (R(g)) of Hc in the hexameric form only slightly increase upon copper removal,
      whereas a remarkable enhancement in the R(g) value is observed for the CaeSS2
      monomer. CD measurements in the far- and near-UV region indicate that removal of
      copper only marginally affects the conformation of the hexameric Hc. Instead,
      copper depletion in the CaeSS2 strongly alters the tertiary structure of the
      monomer (near-UV CD), even though it is almost inconsequential on the secondary
      structure content (far-UV CD). These findings are fully consistent with the
      results of limited proteolysis experiments showing that the hexameric Hc is
      similarly resistant to proteolysis by trypsin both in the holo- and apo-form.
      Conversely, the apo-form of CaeSS2 monomer is much more susceptible to
      proteolytic attack by trypsin than the holo-form. Based on SAXS measurements, the
      concentration-dependent oligomerization process for apo-CaeSS2 has been analyzed
      on the basis of a thermodynamic model involving a concentration-dependent
      equilibrium between a monomer in a native-like and an hexameric aggregate of
      monomers.

PMID- 15950170
TI  - Human intestinal and lung cell lines exposed to beta-carotene show a large
      variation in intracellular levels of beta-carotene and its metabolites.
AB  - Although in vitro models are often used in beta-carotene research, knowledge
      about the uptake and metabolism of beta-carotene in cell lines is lacking. We
      measured by HPLC the intracellular levels of beta-carotene and its metabolites in
      9 human intestinal and lung cell lines after exposure to 1 microM beta-carotene
      during 2, 6, 30, 54 h, and 3 weeks. In three colorectal carcinoma cell lines only
      low levels of beta-carotene could be detected and an apparent linear increase in
      intracellular beta-carotene was observed during the whole exposure period of 3
      weeks. The remaining cell lines (an SV40 transformed colon cell line, a small
      intestinal carcinoma cell line and several lung cell lines) had medium or high
      intracellular beta-carotene levels. In these cell lines intracellular beta
      carotene quickly increased during the first 54 h of exposure and after 3 weeks no
      further increase was observed, suggesting a stable level of beta-carotene after
      54 h. Estimated intracellular concentrations at steady-state levels varied
      between 2 and 5 microM (low) or 9 and 55 microM (medium/high). Our results seem
      to indicate that an active uptake mechanism of beta-carotene exists in at least a
      subset of cell lines. Seven different beta-carotene metabolites were detected in
      the various cell lines (cis-carotene, retinol, three epoxy-carotenes, and two
      retinyl esters). Metabolite levels were the highest in cells with medium or high
      beta-carotene levels. Each cell line appeared to have a distinct metabolite
      profile. No intestinal or lung specific pattern could be found, but two epoxy
      carotene metabolites were not detectable in the colon cell lines.

PMID- 15950171
TI  - Effect of denaturants on multisite and unisite ATP hydrolysis by bovine heart
      submitochondrial particles with and without inhibitor protein.
AB  - The effect of guanidinium hydrochloride (GdnHCl) on multisite and unisite ATPase
      activity by F0F1 of submitochondrial particles from bovine hearts was studied. In
      particles without control by the inhibitor protein, 50 mM GdnHCl inhibited
      multisite hydrolysis by about 85%; full inhibition required around 500 mM. In the
      range of 500-650 mM, GdnHCl enhanced the rate of unisite catalysis by promoting
      product release; it also increased the rate of hydrolysis of ATP bound to the
      catalytic site without GdnHCl. GdnHCl diminished the affinity of the enzyme for
      aurovertin. The effects of GdnHCl were irreversible. The results suggest that
      disruption of intersubunit contacts in F0F1 abolishes multisite hydrolysis and
      stimulates of unisite hydrolysis. Particles under control by the inhibitor
      protein were insensitive to concentrations of GdnHCl that induce the
      aforementioned alterations of F0F1 free of inhibitor protein, indicating that the
      protein stabilizes the global structure of particulate F1.

PMID- 15950172
TI  - Trabecular structure of the condyle of the jaw joint in young and mature sheep: a
      comparative histomorphometric reference.
AB  - Much of the literature regarding arthrotic changes in the temporomandibular joint
      (TMJ) is based on the assumption, rather than the demonstration, that joint
      degeneration is pathologically and biochemically similar to that which has been
      described for other arthrodial joints. Understanding such changes is axiomatic of
      an understanding of the specific histomorphometric structure of the normal TMJ,
      in particular the condyle. Unfortunately, very little has been established about
      the trabecular bone patterns in the mandibular condyle as it develops. As a
      consequence of the obvious practical difficulties in investigations of the human
      TMJ, the sheep has been variously used as an animal model. In order to augment a
      fuller characterisation of this animal model, this study focuses on the
      quantitative histomorphometries of the trabeculae in the mandibular condyles of
      young and mature sheep. Quantitative histomorphometric analyses of condylar
      trabeculae were performed on histological sections prepared from mature and young
      sheep condyles. Lateral, central and medial sagittal sections, and anterior and
      posterior coronal sections of the condyle were analysed using a Quantimet 500MC
      image analysis system that had been programmed to provide structural index values
      of trabecular bone volume, surface, thickness, separation and number. Analysis of
      histoquantitation data revealed a significant concordance in bone structural
      index values between lateral, central and medial regions in young and mature
      sheep as well as anterior and posterior regions in young sheep. Moreover, there
      was little significant variation between similar regions in the respective age
      groups. This study provides the first comparative histomorphometric quantitative
      analysis of the trabeculae in the mandibular condyle of both young and mature
      sheep. The findings of this study reinforce the appropriateness of the sheep TMJ
      as a model in previous experimental studies of the bony architecture of the
      condyle.

PMID- 15950173
TI  - Photosynthetic activity of far-red light in green plants.
AB  - We have found that long-wavelength quanta up to 780 nm support oxygen evolution
      from the leaves of sunflower and bean. The far-red light excitations are
      supporting the photochemical activity of photosystem II, as is indicated by the
      increased chlorophyll fluorescence in response to the reduction of the
      photosystem II primary electron acceptor, Q(A). The results also demonstrate that
      the far-red photosystem II excitations are susceptible to non-photochemical
      quenching, although less than the red excitations. Uphill activation energies of
      9.8+/-0.5 kJ mol(-1) and 12.5+/-0.7 kJ mol(-1) have been revealed in sunflower
      leaves for the 716 and 740 nm illumination, respectively, from the temperature
      dependencies of quantum yields, comparable to the corresponding energy gaps of
      8.8 and 14.3 kJ mol(-1) between the 716 and 680 nm, and the 740 and 680 nm light
      quanta. Similarly, the non-photochemical quenching of far-red excitations is
      facilitated by temperature confirming thermal activation of the far-red quanta to
      the photosystem II core. The observations are discussed in terms of as yet
      undisclosed far-red forms of chlorophyll in the photosystem II antenna, reversed
      (uphill) spill-over of excitation from photosystem I antenna to the photosystem
      II antenna, as well as absorption from thermally populated vibrational sub-levels
      of photosystem II chlorophylls in the ground electronic state. From these three
      interpretations, our analysis favours the first one, i.e., the presence in intact
      plant leaves of a small number of far-red chlorophylls of photosystem II. Based
      on analogy with the well-known far-red spectral forms in photosystem I, it is
      likely that some kind of strongly coupled chlorophyll dimers/aggregates are
      involved. The similarity of the result for sunflower and bean proves that both
      the extreme long-wavelength oxygen evolution and the local quantum yield maximum
      are general properties of the plants.

PMID- 15950174
TI  - Phase behavior of freeze-dried phospholipid-cholesterol mixtures stabilized with
      trehalose.
AB  - A study is presented of the role of cholesterol content on the gel-to-liquid
      crystalline phase transition of freeze-dried liposomes stabilized with trehalose,
      a well known lyoprotectant. The phospholipids considered in this work, DPPC and
      DPPE, belong to the two predominant phospholipid species found in numerous
      biological membranes. Cholesterol is found in abundance in mammalian plasma
      membranes. DSC measurements reveal that cholesterol-containing liposomes exhibit
      multiple phase transitions upon dehydration. Addition of trehalose to these
      systems lowers the phase transition temperature and limits the phase separation
      of the lipidic components upon freeze-drying. This work provides strong evidence
      for the effectiveness of trehalose in stabilizing cholesterol-containing
      membranes upon lyophilization.

PMID- 15950175
TI  - Facial expression of emotions in borderline personality disorder and depression.
AB  - Borderline personality disorder (BPD) is characterized by marked problems in
      interpersonal relationships and emotion regulation. The assumption of emotional
      hyper-reactivity in BPD is tested regarding the facial expression of emotions, an
      aspect highly relevant for communication processes and a central feature of
      emotion regulation. Facial expressions of emotions are examined in a group of 30
      female inpatients with BPD, 27 women with major depression and 30 non-patient
      female controls. Participants were videotaped while watching two short movie
      sequences, inducing either positive or negative emotions. Frequency of emotional
      facial expressions and intensity of happiness expressions were examined, using
      the Emotional Facial Action Coding System (EMFACS-7, Friesen & Ekman, EMFACS-7:
      Emotional Facial Action Coding System, Version 7. Unpublished manual, 1984).
      Group differences were analyzed for the negative and the positive mood-induction
      procedure separately. Results indicate that BPD patients reacted similar to
      depressed patients with reduced facial expressiveness to both films. The highest
      emotional facial activity to both films and most intense happiness expressions
      were displayed by the non-clinical control group. Current findings contradict the
      assumption of a general hyper-reactivity to emotional stimuli in patients with
      BPD.

PMID- 15950176
TI  - Cognitive characteristics of patients with borderline personality disorder:
      development and validation of a self-report inventory.
AB  - Based on cognitive concepts of personality disorders as well as on the bio-social
      model of borderline personality disorder (BPD), a 34-item instrument, the
      questionnaire of thoughts and feelings (QTF) was developed for the assessment of
      feelings, strategic cognitions, and assumptions characteristic for BPD. In
      different studies, item- and factor analyses were conducted with a dataset of
      N=646 clinical and non-clinical participants. Cross-sectional data as well as
      longitudinal data are available including several other measures on personality
      and personality disorders: DSM-IV SCID II dimensional score, a personality
      inventory (PSSI), the German version of the personality disorder beliefs
      questionnaire (PBQ), as well as overall severity of symptoms (GSI) of the SCL-90
      R. Internal consistency of the scale is excellent, Cronbach's alpha=0.91. One
      week test-retest reliability was also high r(tt)=0.81. Good convergent and
      discriminant validity was obtained for correlation with SCID dimensional scores
      and discrimination of BDP patients and other clinical and non-clinical groups. A
      comparison of scores in a sample of 26 patients with BPD during crisis
      intervention and 8 months later indicated the sensitivity of the QTF to measure
      change over time. Overall, the questionnaire appears to be a methodologically
      sound measure, valuable for research purposes as well as in clinical practice.

PMID- 15950177
TI  - Tandem repeat L-rhamnose-binding lectin from the skin mucus of ponyfish,
      Leiognathus nuchalis.
AB  - Two lactose-binding lectins (PFL-1 and -2) were identified in the skin mucus of
      ponyfish, Leiognathus nuchalis. The molecular masses of PFL-1 and -2 were
      estimated to be 24 and 30kDa, respectively. Cloning of the PFL-1 cDNA
      demonstrated its unique tandem repeat structure composed of two homologous
      domains with 41.7% internal identity. Furthermore, PFL-1 exhibited homology with
      L-rhamnose-binding lectins previously purified from the eggs of fish and sea
      urchins. The N-terminal amino acid sequence of PFL-2 was similar to that of PFL
      1, suggesting that this protein is an isotype of PFL-1. The PFL-1 gene was
      expressed in the skin, an important line of defense against pathogens in fish,
      but was not expressed in any of the other tissues tested here. PFL-1 is the
      fourth type of fish skin mucus lectin to be identified, suggesting that different
      species of fish express different types of lectin in their skin mucus.

PMID- 15950178
TI  - Prokaryotic expression of bone sialoprotein and identification of casein kinase
      II phosphorylation sites.
AB  - Bone sialoprotein is an extracellular noncollagenous acidic protein that plays a
      role in bone mineralization and remodeling. Its expression is restricted to
      mineralized tissues and is subjected to variety of posttranslational
      modifications including phosphorylation and glycosylation. We have expressed the
      full-length and half domains of bovine bone sialoprotein in a prokaryotic system
      and identified the phosphorylation sites of casein kinase II. The N-terminal
      automated solid-phase sequencing defined four phosphorylated peptides: residues
      28-38 (LEDS(P)EENGVFK), 51-86
      (FYPELKRFAVQSSS(P)DS(P)S(P)EENGNGDS(P)S(P)EEEEEEEETS(P)), 151-165
      (EDES(P)DEEEEEEEEEE), and 295-305 (GRGYDS(P)YDGQD). Nine phosphoserines were
      identified within the four peptides. Seven of them were in the N-terminus (S31,
      S64, S66, S67, S75, S76, and S86) and two were in the C-terminus (S154 and S300)
      of the protein.

PMID- 15950179
TI  - Epstein-Barr virus immediate-early proteins BZLF1 and BRLF1 alter mitochondrial
      morphology during lytic replication.
AB  - Epstein-Barr virus (EBV) is a human DNA virus that is responsible for the
      syndrome infectious mononucleosis, and is associated with several forms of
      cancer. During both lytic and latent viral infection, viral proteins manipulate
      the host's cellular components to aid in viral replication and maintenance. Here,
      it is demonstrated that induction of EBV lytic replication results in a dramatic
      reorganization of mitochondria accompanied by a significant alteration of
      mitochondrial membrane potential and a rapid and transient increase in the
      microtubular cytoskeleton. Moreover, we show that expression of the EBV immediate
      early genes BZLF1 and BRLF1 contributes to the mitochondrial alteration but not
      the increase in the microtubule cytoskeleton, suggesting that the mechanism for
      the observed cytoplasmic restructuring involves a number of coordinated viral and
      host proteins.

PMID- 15950180
TI  - Anti-citrullinated collagen type I antibody is a target of autoimmunity in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is one of the most common autoimmune diseases, but its
      autoimmune mechanisms are not clearly understood. Recently, anti-citrullinated
      peptide antibodies have been specifically observed in sera of RA patients.
      Furthermore, we identified RA-susceptible variant in a gene encoding
      citrullinating enzyme, peptidylarginine deiminase type 4 (PADI4). Therefore, we
      hypothesized that proteins which are modified in RA synovium by PADI4 act as
      autoantigens. Subsequently, we obtained human collagen type I (huCI) as one of
      the autoantigens using a RA synoviocyte cDNA library by immunoscreening. We also
      investigated that the levels of anti-citrullinated huCI were significantly higher
      in RA patient sera than in normal control sera with high specificity (99%) and
      positively correlated with the levels of anti-cyclic citrullinated peptide (anti
      CCP) antibodies. We concluded that huCI is a novel substrate protein of PADIs and
      that citrullinated huCI is a candidate autoantigen of RA.

PMID- 15950181
TI  - Identification of the human DEAD-box protein p68 as a substrate of Tlk1.
AB  - The activity of the human protein kinase Tlk1 is down-regulated within minutes
      after exposure of cells to ionizing radiation. In order to identify signaling
      pathways which might be relevant in the radiation response of mammalian cells we
      screened nuclear proteins for substrates of Tlk1. Among several proteins one
      could be identified as p68 RNA helicase. Furthermore, it could be shown that Tlk1
      phosphorylates immunoprecipitated p68. The phosphorylation of the C-terminal
      fragment of p68 by rTlk1 reduced its affinity to single stranded RNA in a gel
      shift assay. In addition, it could be demonstrated that increasing the Tlk1
      activity in HT1080 cells by forced Tlk1 overexpression leads to an increased
      phosphorylation of endogenous p68, arguing that p68 might be a physiological
      substrate of Tlk1. These findings open the possibility that Tlk1 might
      participate in diverse biologic functions like cell growth and differentiation,
      pre-mRNA splicing, and transcriptional coactivation.

PMID- 15950182
TI  - Nucleophosmin/B23-binding peptide inhibits tumor growth and up-regulates
      transcriptional activity of p53.
AB  - The Rev peptide that binds to nucleophosmin/B23 with the highest affinity
      exhibited the greatest cytotoxicity on Ras-3T3 cells and inhibited tumor growth
      most effectively in nude mice. The efficiency of colony formation in soft agar of
      Ras-3T3 cells was significantly inhibited by treatment with Rev peptide. In
      addition, Rev peptide could potentiate the doxorubicin-induced decrease of
      cellular viability in U1 bladder cancer cells and inhibition of tumor growth in
      nude mice. Treatment of Rev peptide increased protein expression and
      transcriptional activity of p53 and inhibited the nucleophosmin/B23-mediated PCNA
      promoter activation. Peptides having high affinity of binding to molecular
      targets such as nucleophosmin/B23 represent a potentially useful approach to anti
      cancer biotherapeutics.

PMID- 15950184
TI  - Biophysical properties of menthol-activated cold receptor TRPM8 channels.
AB  - The temperature-sensitive transient receptor potential channel, TRPM8, was
      recently cloned and found to be activated by cold and menthol. Whole-cell
      recordings show that TRPM8 is permeable to multiple cations and exhibits a strong
      outward rectification. Here, we examine the mechanism underlying menthol-evoked
      current rectification of TRPM8 transiently expressed in tsA-201 cells at room
      temperature ( approximately 25 degrees C). Whole-cell currents (ruptured, bath:
      Na(+), K(+), Ca(2+), or Ba(2+); pipette: KCl) exhibited a strong outward
      rectification in the presence of menthol, consistent with previous studies. The
      outward K(+) current was reduced in the presence of external Ca(2+) or Ba(2+).
      Single-channel recordings (cell-attached) showed that menthol induced brief
      channel openings with two conducting states in the voltage range between -80 and
      +60mV. The small current (i(S)) conducted both monovalent and divalent ions, and
      the large one (i(L)) predominantly monovalent ions. The i-V plot for Ca(2+) was
      weakly outward rectifying, whereas those for monovalent ions were linear. The
      i(S) may result in the divalent ion-induced reduction of the whole-cell outward
      current. The open probability (P(o)) in all ion conditions tested was low at
      negative voltages and increased with depolarization, accounting for the small
      inward currents observed at the whole-cell level. In conclusion, our results
      indicate that menthol induced steep outward rectification of TRPM8 results from
      the voltage-dependent open channel probability and the permeating ion-dependent
      modulation of the unitary channel conductance.

PMID- 15950183
TI  - The evolution of a genetic locus encoding small serine proteinase inhibitors.
AB  - We previously identified a locus on human chromosome 20 that encompasses 14 genes
      of postulated WFDC-type proteinase inhibitors with a potential role in innate
      immunity. In an extended study, homologous loci are here described on mouse
      chromosome 2, rat chromosome 3, and dog chromosome 24. As in humans, the murine
      and canine loci are divided into two sub-loci separated by 0.2Mb. The majority of
      genes are conserved in all species, but there are also species-specific gains and
      losses of genes, e.g., several duplications have yielded four SLPI genes in the
      rat and, most surprisingly, there is no murine elafin gene. Two human pseudogenes
      were identified due to the discovery of functional rodent genes. The conservation
      of different WFDC domains varies considerably, and it is hypothesized that this
      reflects a dual role of WFDC inhibitors in natural immunity, which is directed
      both against microbes and proinflammatory cells.

PMID- 15950185
TI  - A novel six-transmembrane protein hhole functions as a suppressor in MAPK
      signaling pathways.
AB  - Src homology 3 (SH3) domains mediate intracellular protein-protein interactions
      through the recognition of proline-rich sequence motifs on cellular proteins.
      Such protein-protein interactions can activate the protein kinase cascade that
      mediates MAPK signaling pathway. The human hole gene, hhole, is a 319-amino acid
      six-transmembrane protein with proline-rich C-terminal motifs and N-terminal ERK
      binding domains (D-domains). The hhole protein is highly conserved in evolution
      across different species from elegent, mouse to human. Northern blot analysis
      indicates that hhole is expressed in heart, liver, skeletal muscle, and pancreas
      at adult stages and in most of the examined embryonic tissues, especially at a
      higher level in heart. Using a GFP-labeled hhole protein, we demonstrate that
      hhole is localized in plasma membrane or proximal region of the membrane.
      Overexpression of hhole in COS-7 cells strongly inhibited the transcriptional
      activities of AP-1 and SRE while deletion of the C-terminal proline-rich motifs
      or the N-terminal ERK binding D-domain motifs reduced the repressive activity of
      the gene. These results suggest that the hhole protein may interact with SH3
      domain proteins or ERKs to mediate signaling pathways/networks that lead to the
      suppression of AP-1 and SRE.

PMID- 15950186
TI  - Angioarrestin: a unique angiopoietin-related protein with anti-angiogenic
      properties.
AB  - The process of angiogenesis plays a pivotal role in embryogenesis, wound healing,
      and tumorigenesis through the growth of new blood vessels from pre-existing
      vasculature. Among the angiogenic factors recently identified as specific for
      vascular endothelium are the angiopoietins. In depth characterization of the
      angiopoietins has allowed investigators to better understand the molecular basis
      of blood vessel formation and vascular endothelial cell function. In this review,
      we describe angiopoietins and related family members, with particular emphasis on
      a recently identified protein known as angioarrestin. Our investigations clearly
      demonstrate that angioarrestin is an anti-angiogenic molecule. The effects of
      angioarrestin on tumor cell progression and specific aspects of the angiogenic
      cascade in in vitro models are further discussed.

PMID- 15950187
TI  - Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis
      inhibitors found in hypovascular connective tissues.
AB  - In tissues and/or organs of mesenchymal origin, the vasculature is usually well
      developed. However, there are certain hypovascular tissues that exhibit powerful
      anti-angiogenic resistance, implying the presence of tissue-type specific
      inhibitors of angiogenesis. Hyaline cartilage is one example, and several anti
      angiogenic factors have been purified from cartilage. We previously identified
      chondromodulin-I (ChM-I) as a tissue-specific inhibitor of angiogenesis in fetal
      bovine cartilage. ChM-I is specifically expressed in the avascular regions of the
      growth-plate and cartilaginous bone rudiments in embryos. Recently, we cloned a
      novel type II transmembrane protein, tenomodulin (TeM), having a domain
      homologous to ChM-I at its C-terminus. TeM turned out to be expressed
      specifically in other hypovascular structures in the mesenchyme, such as the
      epimysium, tendon, and ligaments. In this overview, we discuss the structural
      characteristics of this class of anti-angiogenic molecules and their
      pathophysiological role in the control of vascularity.

PMID- 15950188
TI  - Structural analysis of catechin derivatives as mammalian DNA polymerase
      inhibitors.
AB  - The inhibitory activities against DNA polymerases (pols) of catechin derivatives
      (i.e., flavan-3-ols) such as (+)-catechin, (-)-epicatechin, (-)-gallocatechin, (
      )-epigallocatechin, (+)-catechin gallate, (-)-epicatechin gallate, (-)
      gallocatechin gallate, and (-)-epigallocatechin gallate (EGCg) were investigated.
      Among the eight catechins, some catechins inhibited mammalian pols, with EGCg
      being the strongest inhibitor of pol alpha and lambda with IC(50) values of 5.1
      and 3.8 microM, respectively. EGCg did not influence the activities of plant
      (cauliflower) pol alpha and beta or prokaryotic pols, and further had no effect
      on the activities of DNA metabolic enzymes such as calf terminal deoxynucleotidyl
      transferase, T7 RNA polymerase, and bovine deoxyribonuclease I. EGCg-induced
      inhibition of pol alpha and lambda was competitive with respect to the DNA
      template-primer and non-competitive with respect to the dNTP (2'
      deoxyribonucleotide 5'-triphosphate) substrate. Tea catechins also suppressed TPA
      (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation, and the tendency of
      the pol inhibitory activity was the same as that of anti-inflammation. EGCg at
      250 microg was the strongest suppressor of inflammation (65.6% inhibition) among
      the compounds tested. The relationship between the structure of tea catechins and
      the inhibition of mammalian pols and inflammation was discussed.

PMID- 15950189
TI  - Erk phosphorylates threonine 42 residue of ribosomal protein S3.
AB  - The ribosomal protein S3 (rpS3) is involved in ribosome biogenesis as a member of
      ribosomal small subunit and also plays a role in the repair of damaged DNA.
      Extracellular signal-regulated kinase (Erk), a MAP kinase, is known to play
      important roles in the regulation of cell growth, differentiation, and apoptosis.
      In this study, the sequence analysis of rpS3 protein revealed that this protein
      has a putative FXFP motif which is believed to be an Erk binding site. Indeed,
      the motif was demonstrated as an Erk binding site by co-immunoprecipitation. In
      addition to this, it was revealed that Erk specifically phosphorylated Thr 42
      residue of rpS3 in vitro and in vivo using the various mutants of rpS3. Taken
      together, rpS3 appears to be phosphorylated by activated Erk in proliferating
      cells, resulting in the decreased interaction between two proteins.

PMID- 15950190
TI  - Screening of drugs by FRET analysis identifies inhibitors of SARS-CoV 3CL
      protease.
AB  - SARS-CoV 3CL protease is essential for viral protein processing and is regarded
      as a good drug target to prevent SARS-CoV replication. In the present study, we
      established a high-throughput FRET technique for screening for anti-SARS-CoV 3CL
      protease drugs. Of a thousand existing drugs examined, hexachlorophene was
      identified as the most potent in inhibiting SARS-CoV 3CL protease. Further
      characterization showed that it was effective at micromolar concentrations (K(i)
      = 4 microM). The binding mode was competitive, and the inhibitory effect was
      dependent on preincubation time. Two other drugs, triclosan and nelfinavir, were
      about 10 times less potent. The structure-based search and biological evaluation
      of various hexachlorophene analogues were described. These analogues gave optimal
      inhibitory activity against SARS-CoV 3CL protease with IC(50) values ranging from
      7.6 to 84.5 microM. Optimization of hexachlorophene analogues was shown to
      provide several active 3CL protease inhibitors that function as potential anti
      SARS agents.

PMID- 15950191
TI  - ZNF649, a novel Kruppel type zinc-finger protein, functions as a transcriptional
      suppressor.
AB  - Cardiac differentiation involves a cascade of coordinated gene expression that
      regulates cell proliferation and matrix protein formation in a defined temporo
      spatial manner. Many of the KRAB-ZFPs are involved in cardiac development or
      cardiovascular diseases. Here we report the identification and characterization
      of a novel human zinc-finger gene named ZNF649. The cDNA of ZNF649 is 3176 bp,
      encoding a protein of 505 amino acids in the nuclei. Northern blot analysis
      indicates that ZNF649 is expressed in most of the examined human adult and
      embryonic tissues. ZNF649 is a transcription suppressor when fused to GAL-4 DNA
      binding domain and cotransfected with VP-16. Overexpression of ZNF649 in COS-7
      cells inhibits the transcriptional activities of SRE and AP-1. Deletion analysis
      with a series of truncated fusion proteins indicates that the KRAB motif is a
      basal repression domain when the truncated fusion proteins were assayed for the
      transcriptional activities of SRE and AP-1. These results suggest that ZNF649
      protein may act as a transcriptional repressor in mitogen-activated protein
      kinase signaling pathway to mediate cellular functions.

PMID- 15950192
TI  - Olfactory-like receptor cDNAs are present in human lingual cDNA libraries.
AB  - Olfactory and pheromone receptors (ORs) constitute a large family of G-protein
      coupled receptors involved in the detection and transduction of odorant signals.
      Using degenerated primers complementary to the highly conserved transmembrane
      domains II, III, VI, and VII within this protein family, Gaudin et al. have
      recently described the expression of several OR genes in foetal human tongue.
      Among the nine genes identified in human foetal tongue (HTPCR06, HGMP07I, JCG6,
      TPCR85, JCGI1, JCG2, JCG3, JCG5, and JCG9), only four (HTPCR06, HGMP07I, JCG3,
      and JCG5) were found to be expressed in adult tongue, suggesting that ORs might
      perform developmental functions in this organ. The objective of our work was to
      obtain additional information about the expression of olfactory-like genes in
      human tongue. In the present study, the synthesis and the screening of a cDNA
      library from epithelial cells of human adult tongue is reported. Two kinds of PCR
      analysis were performed. First, partial olfactory-like receptor cDNAs amplified
      with the degenerated primers used by Gaudin et al. were cloned and described.
      Second, a comparison of the expression profiles of the olfactory-like receptor
      genes previously identified before was carried out using specific primers. Among
      the genes studied we found that four genes (HTPCR06, JCG3, JCG5, and JCG6) are
      expressed in epithelial cells of the surface of the adult tongue. Additionally,
      we show that three olfactory-like receptor genes OR7A5/HTPCR2, OR6Q1, and
      OR7C1/TPCR86 are also expressed in these cells.

PMID- 15950193
TI  - Hepatocyte growth factor is constitutively produced by donor-derived bone marrow
      cells and promotes regeneration of pancreatic beta-cells.
AB  - Recent studies have demonstrated that the transplantation of bone marrow cells
      following diabetes induced by streptozotocin can support the recovery of
      pancreatic b-cell mass and a partial reversal of hyperglycemia. To address this
      issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling
      pathway was involved in the recovery of b-cell injury after bone marrow
      transplantation (BMT). In this model, donor-derived bone marrow cells were
      positive for HGF immunoreactivity in the recipient spleen, liver, lung, and
      pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were
      maintained at a high value.The frequency of c-Met expression and its
      proliferative activity and differentiative response in the pancreatic ductal
      cells in the BMT group were greater than those in the PBS-treated group,
      resulting in an elevated number of endogenous insulin-producing cells. The
      induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic
      regeneration in diabetic rats.

PMID- 15950194
TI  - Orientation of oxazolidinones in the active site of monoamine oxidase.
AB  - Oxazolidinone inhibitors of monoamine oxidase (MAO) and oxazolidinone
      antibacterials are two distinct classes of drug, often with linear structures and
      overlapping activities for some derivatives. By synthesizing novel dimerised
      derivatives with identical substitution of the two C-5 side chains, we have
      obtained experimental evidence for the orientation of oxazolidinones in the
      active site of MAO A. Two types of spectral changes, either increasing the
      absorbance at 510 nm or decreasing it at 495 nm depending on the group nearest to
      the flavin cofactor, were seen on ligand binding to MAO A. Side chain derivatives
      with amine substituents are very poor substrates so that it was possible to
      examine the spectral change due to binding of a substrate before reduction of the
      flavin occurred. Binding of these amino derivative substrates to MAO A induced a
      spectral change characterized by a strong decrease in absorbance at 495 nm. These
      substrates reduced the enzyme fully without any trace of a semiquinone
      intermediate. Only oxazolidinone inhibitors with a bromo-imidazole substituent
      increased the yield of semiquinone intermediate obtained during chemical
      reduction. In accord with the experimental data, results of docking experiments
      showed that binding of the oxazolidinone ring in the aromatic cage close to the
      flavin was favored and that the nitrogen of the derivatives that were substrates
      was within van der Waals distance of N-5 of the flavin.

PMID- 15950195
TI  - Use-dependent blockade of Cav2.2 voltage-gated calcium channels for neuropathic
      pain.
AB  - The translocation of extracellular calcium (Ca(2+)) via voltage-gated Ca(2+)
      channels (VGCCs) in neurons is involved in triggering multiple physiological cell
      functions but also the abnormal, pathophysiological responses that develop as a
      consequence of injury. In conditions of neuropathic pain, VGCCs are involved in
      supplying the signal Ca(2+) important for the sustained neuronal firing and
      neurotransmitter release characteristic of these syndromes. Preclinical data have
      identified N-type VGCCs (Ca(v)2.2) as key participants in contributing to these
      Ca(2+) signaling events and clinical data with the peptide blocker Prialt have
      now validated Ca(v)2.2 as a bona fide target for future drug discovery efforts to
      identify new and novel therapeutics for neuropathic pain. Imperative for the
      success of such an endeavor will be the ability to identify compounds selective
      for Ca(v)2.2, versus other VGCCs, but also compounds which demonstrate effective
      blockade during the pathophysiological states of neuropathic pain without
      compromising channel activity associated with sustaining normal housekeeping
      cellular functions. An approach to obtain this research target profile is to
      identify compounds, which are more potent in blocking Ca(v)2.2 during higher
      frequencies of firing as compared to the slower more physiologically-relevant
      frequencies. This may be achieved by identifying compounds with enhanced potency
      for the inactivated state of Ca(v)2.2. This commentary explores the rationale and
      options for engineering a use-dependent blocker of Ca(v)2.2. It is anticipated
      that this use-dependent profile of channel blockade will result in new chemical
      entities with an improved therapeutic ratio for neuropathic pain.

PMID- 15950196
TI  - Inhibition of cyclooxygenase with indomethacin phenethylamide reduces
      atherosclerosis in apoE-null mice.
AB  - Non-selective inhibition of cyclooxygenase (COX) has been reported to reduce
      atherosclerosis in both rabbit and murine models. In contrast, selective
      inhibition of COX-2 has been shown to suppress early atherosclerosis in LDL
      receptor null mice but not more advanced lesions in apoE deficient (apoE(-/-))
      mice. We investigated the efficacy of the novel COX inhibitor indomethacin
      phenethylamide (INDO-PA) on the development of different stages of
      atherosclerotic lesion formation in female apoE(-/-) mice. INDO-PA, which is
      highly selective for COX-2 in vitro, reduced platelet thromboxane production by
      61% in vivo, indicating partial inhibition of COX-1 in vivo. Treatment of female
      apoE(-/-) mice with 5mg/kg INDO-PA significantly reduced early to intermediate
      aortic atherosclerotic lesion formation (44 and 53%, respectively) in both the
      aortic sinus and aorta en face compared to controls. Interestingly, there was no
      difference in the extent of atherosclerosis in the proximal aorta in apoE(-/-)
      mice treated from 11 to 21 weeks of age with INDO-PA, yet there was a striking
      (76%) reduction in lesion size by en face analysis in these mice. These studies
      demonstrate the ability of non-selective COX inhibition with INDO-PA to reduce
      early to intermediate atherosclerotic lesion formation in apoE(-/-) mice,
      supporting a role for anti-inflammatory approaches in the prevention of
      atherosclerosis.

PMID- 15950197
TI  - Bipolar diagnoses in community mental health: Achenbach Child Behavior Checklist
      profiles and patterns of comorbidity.
AB  - BACKGROUND: There are converging findings about pediatric bipolar disorder (PBD)
      in terms of associated comorbidity and behavior problem profiles on the Achenbach
      Child Behavior Checklist (CBCL). However, no study has examined clinical or
      demographic characteristics of youths clinically diagnosed with bipolar disorder
      in a low-income, diverse community clinical sample. METHODS: Archival data (N =
      3086 cases) from six urban community mental health centers (CMHC) were reviewed
      to determine the base rate of bipolar disorder and the demographic and clinical
      characteristics (comorbidity and CBCL profiles) associated with the diagnosis.
      RESULTS: Roughly 6% of the sample received clinical diagnoses of PBD. Patterns of
      comorbidity and CBCL profiles were highly similar to published samples. However,
      elevated CBCL scores were not specific to bipolar disorder, since they were also
      frequently high for nonbipolar cases. CONCLUSIONS: There appears to be
      substantial convergence between the demographic and clinical characteristics of
      cases clinically diagnosed with PBD versus those diagnosed with semistructured
      research interviews, strengthening the validity of both sets of diagnoses. At the
      same time, the CBCL appears to do poorly discriminating clinical diagnoses of
      PBD, due to the pervasive externalizing behavior problems in CMHC samples and the
      variable presentation of PBD cases.

PMID- 15950198
TI  - Age-dependent susceptibility of adult hippocampal cell proliferation to chronic
      psychosocial stress.
AB  - Stress inhibits neurogenesis in the adult dentate gyrus. It is not known,
      however, whether age has any influence on this process. We subjected adult male
      tree shrews to 5 weeks of psychosocial stress, after which dentate cytogenesis
      was determined using BrdU immunohistochemistry. We found that older animals were
      significantly more vulnerable to the adverse effect of stress on dentate cell
      proliferation.

PMID- 15950199
TI  - Low intracerebroventricular doses of cholinotoxin AF64A do not affect the
      morphology of gonadotropin hormone-releasing hormone (GnRH)-immunoreactive fibers
      in the rat septum.
AB  - Ethylcholine aziridinium (AF64A) induces cholinergic lesion in animal models of
      AD. Although higher concentrations of AF64A are known to induce nonspecific,
      cholinergic, and non-cholinergic lesions, low concentrations are believed to be
      selectively cholinotoxic. However, morphological evidence of this phenomenon has
      not been demonstrated yet. The present study demonstrates that while AF64A
      damaged septal cholinergic fibers, periventricular GnRH-immunoreactive fibers
      remained intact, confirming the highly selective cholinotoxicity of AF64A at
      appropriate concentrations.

PMID- 15950200
TI  - Dominant-negative I(Ks) suppression by KCNQ1-deltaF339 potassium channels linked
      to Romano-Ward syndrome.
AB  - OBJECTIVE: Hereditary long QT syndrome (LQTS) is a genetically heterogeneous
      disease characterized by prolonged QT intervals and an increased risk for
      ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated
      potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is
      associated with two different entities of LQTS, the autosomal-dominant Romano
      Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen
      syndrome (JLNS) characterized by bilateral deafness in addition to cardiac
      arrhythmias. In this study, we investigate and discuss dominant-negative I(Ks)
      current reduction by a KCNQ1 deletion mutation identified in a RWS family.
      METHODS: Single-strand conformation polymorphism analysis and direct sequencing
      were used to screen LQTS genes for mutations. Mutant KCNQ1 channels were
      heterologously expressed in Xenopus oocytes, and potassium currents were recorded
      using the two-microelectrode voltage clamp technique. RESULTS: A heterozygous
      deletion of three nucleotides (CTT) identified in the KCNQ1 gene caused the loss
      of a single phenylalanine residue at position 339 (KCNQ1-deltaF339).
      Electrophysiological measurements in the presence and absence of the regulatory
      beta-subunit KCNE1 revealed that mutant and wild type forms of an N-terminal
      truncated KCNQ1 subunit (isoform 2) caused much stronger dominant-negative
      current reduction than the mutant form of the full-length KCNQ1 subunit (isoform
      1). CONCLUSION: This study highlights the functional relevance of the truncated
      KCNQ1 splice variant (isoform 2) in establishment and mode of inheritance in long
      QT syndrome. In the RWS family presented here, the autosomal-dominant trait is
      caused by multiple dominant-negative effects provoked by heteromultimeric
      channels formed by wild type and mutant KCNQ1-isoforms in combination with KCNE1.

PMID- 15950201
TI  - Sphingosylphosphorylcholine-induced vasoconstriction of pulmonary artery:
      activation of non-store-operated Ca2+ entry.
AB  - OBJECTIVE: Sphingosylphosphorylcholine (SPC) is an important lipid mediator that
      has been implicated in vascular disease. As it has not been studied in the
      pulmonary circulation, we examined its mechanisms of action in rat small
      intrapulmonary arteries (IPA). METHODS: IPA were mounted on a myograph for
      recording tension and intracellular Ca2+ concentration ([Ca2+]i). Ca2+
      sensitisation was examined in alpha-toxin permeabilized IPA, and by Western blot
      analysis of MYPT1 phosphorylation. RESULTS: SPC induced a slow but powerful
      vasoconstriction in IPA associated with an elevation in [Ca2+]i, with an EC50 for
      vasoconstriction of 12+/-2 microM. Removal of extracellular Ca2+ increased the
      EC50 to 76+/-33 microM (p<0.01) and abolished the rise in [Ca2+]i. Endothelial
      denudation or inhibition of NO synthase with L-NAME enhanced vasoconstriction.
      Treatment with pertussis toxin or the PLC inhibitor U731223 had no effect on SPC
      induced vasoconstriction. The Rho kinase inhibitor Y27632 reduced SPC-induced
      vasoconstriction by approximately 70% and abolished both SPC-induced Ca2+
      sensitisation in permeabilized IPA and the associated increase in MYPT1
      phosphorylation; Ca2+ sensitisation was substantially inhibited by GDPbetaS. La3+
      and 2-APB, at concentrations previously shown to block capacitative Ca2+ entry in
      IPA, suppressed SPC-induced vasoconstriction to the same extent as removal of
      extracellular Ca2+; residual tension was abolished by Y27632. Diltiazem was
      relatively ineffective. 2-APB also abolished the SPC-induced rise in [Ca2+]i.
      However, treatment with thapsigargin to empty intracellular stores had no effect
      on the elevation of [Ca2+]i induced by SPC. CONCLUSION: We present evidence that
      SPC is a powerful vasoconstrictor of IPA and the novel finding that SPC-induced
      vasoconstriction in IPA is dependent on activation of a Ca2+ entry pathway with a
      similar sensitivity to La3+ and 2-APB as capacitative Ca2+ entry, although its
      activation is not dependent on emptying of PLC/IP3 or thapsigargin-sensitive
      intracellular stores.

PMID- 15950202
TI  - Cellular and molecular mechanisms of sex differences in renal ischemia
      reperfusion injury.
AB  - Renal ischemia-reperfusion (I/R) is an important etiopathological mechanism of
      acute renal failure (ARF). Despite improvements in the treatment of ARF, it is
      associated with significant morbidity and mortality. I/R injury also occurs
      during renal transplantation and leads to reduced allograft survival. Sex
      differences have been found in I/R injury in many different organs including the
      kidney. Women have half the mortality of men in ARF. In animal models also,
      females are protected against renal I/R injury. The mechanisms by which sex
      affects the outcome to renal I/R injury are being actively investigated. This
      review will examine the evidence for gender differences in renal I/R injury and
      discuss the probable mechanisms by which sex affects the renal response to I/R
      injury.

PMID- 15950203
TI  - The estrogen receptor-alpha agonist 16alpha-LE2 inhibits cardiac hypertrophy and
      improves hemodynamic function in estrogen-deficient spontaneously hypertensive
      rats.
AB  - OBJECTIVE: Cardiac mass increases with age and with declining estradiol serum
      levels in postmenopausal women. Although the non-selective estrogen receptor
      alpha and -beta agonist 17beta-estradiol attenuates cardiac hypertrophy in animal
      models and in observational studies, it remains unknown whether activation of a
      specific estrogen receptor subtype (ERalpha or ERbeta) might give similar or
      divergent results. Therefore, we analyzed myocardial hypertrophy as well as
      cardiac function and gene expression in ovariectomized, spontaneously
      hypertensive rats (SHR) treated with the subtype-selective ERalpha agonist
      16alpha-LE2 or 17beta-estradiol. METHODS AND RESULTS: Long-term administration of
      16alpha-LE2 or 17beta-estradiol did not affect elevated blood pressure, but both
      agonists efficiently attenuated cardiac hypertrophy and increased cardiac output,
      left ventricular stroke volume, papillary muscle strip contractility, and cardiac
      alpha-myosin heavy chain expression. The observed effects of E2 and 16alpha-LE2
      were abrogated by the ER antagonist ZM-182780. Improved left ventricular function
      upon 16alpha-LE2 treatment was also observed in cardiac MRI studies. In contrast
      to estradiol and 16alpha-LE2, tamoxifen inhibited cardiac hypertrophy but failed
      to increase alpha-myosin heavy chain expression and cardiac output. CONCLUSIONS:
      These results support the hypothesis that activation of ERalpha favorably affects
      cardiac hypertrophy, myocardial contractility, and gene expression in
      ovariectomized SHR. Further studies are required to determine whether activation
      ERbeta mediates redundant or divergent effects.

PMID- 15950205
TI  - Forced myocardin expression primes cardiac and smooth muscle transcription
      patterning in human mesenchymal stem cells.

PMID- 15950204
TI  - Decreased caveolin-1 in atheroma: loss of antiproliferative control of vascular
      smooth muscle cells in atherosclerosis.
AB  - OBJECTIVE: Proliferation of vascular smooth muscle cells (VSMC) is involved in
      the pathogenesis of primary atherosclerosis and restenosis after angioplasty. On
      the background of the antiproliferative activities of caveolin-1, the present
      study focused on the expression of caveolin-1 in proliferating VSMC of human
      atheroma. METHODS: VSMC were isolated from wild-type (Wt) and caveolin-1 knockout
      mice (Cav-/-). Proliferation of Wt-VSMC after supplementation of serum or Cav-/
      VSMC after adenoviral overexpression of caveolin-1 was documented by either
      Western blot analysis of the cyclin-dependent kinase (Cdk) inhibitor p27kip1 and
      the proliferating cell nuclear antigen (PCNA) or BrdU incorporation. Using
      immunohistochemistry the proliferation of VSMC derived from atheroma of human
      carotid vessels as well as the expression of caveolin-1 in these cells were
      investigated ex vivo. RESULTS: Supplementation of serum to Wt-VSMC resulted in an
      augmented cell cycle entry and a concomitant decrease of caveolin-1 expression.
      Inversely, adenoviral overexpression of caveolin-1 in Cav-/-VSMC inhibited
      cellular proliferation. Corresponding to these in vitro data, the expression of
      caveolin-1 was significantly decreased in proliferating VSMC of human atheroma.
      CONCLUSION: The proliferation of VSMC in vitro and in human atheroma is
      associated with a decrease of caveolin-1 expression. These data suggest that the
      loss of antiproliferative control by caveolin-1 plays a pivotal role in VSMC
      proliferation in atherosclerosis.

PMID- 15950208
TI  - Self-peptide/MHC and TCR antagonism: physiological role and therapeutic
      potential.
AB  - TCR antagonists are peptides that bind MHC molecules and can specifically inhibit
      T cell activation induced by antigens. Studying TCR antagonism has taken an
      important place in immunology for both theoretical and practical reasons.
      Deciphering the mechanism(s) of action of TCR antagonists can yield important
      information about interactions of the TCR with ligands, T cell development, and
      TCR signaling. Moreover, microorganisms may employ TCR antagonism to elude the
      attention of the immune system. Finally, specificity of inhibition makes TCR
      antagonists an ideal tool to seek antigen-specific immunomodulation. Present
      state of knowledge on these topics is reviewed.

PMID- 15950206
TI  - Region-specific, pacing-induced changes in repolarization in rabbit atrium: an
      example of sensitivity to the rare.
AB  - OBJECTIVE: In subsets of patients paroxysmal firing of ectopic foci in pulmonary
      veins or coronary sinus is an important cause of atrial fibrillation. This
      appears to represent a rare event overriding a dominant sinus mechanism to alter
      the rhythmic firing of the atrium. Hence, we tested the hypothesis that a rare
      stimulation pattern might alter the myocardial substrate, making it more
      susceptible to the initiation of arrhythmias. METHODS: In isolated right and left
      rabbit atria, a "rare" burst pacing protocol (BPP) was applied as follows: over 3
      h, preparations were driven for 4.5 min from sinus node (SN) or Bachmann's bundle
      (BB) regions at cycle length (CL)=400 ms followed by 30 s of stimulation from
      coronary sinus (CS) or pulmonary vein (PV) at CL=200 ms. Microelectrodes were
      used to record action potentials at the end of 4.5 min of pacing at CL=400 ms. We
      then intervened with 5-min bigeminal pacing to probe atrial vulnerability to
      arrhythmias: S1 was delivered from SN or BB and S2 from CS or PV, respectively.
      S1-S2 interval was the shortest eliciting a propagated response. RESULTS: BPP
      shortened repolarization in CS and PV regions but not in SN or BB, resulting in
      increased dispersion of repolarization in right and decreased in left atria.
      Propranolol, atropine and losartan failed to alter the decrease in repolarization
      induced by BPP whereas apamin, nifedipine and ryanodine prevented BPP effects.
      Before BPP, bigeminy did not induce arrhythmias in either atrium, but after BPP,
      bigeminy significantly increased the incidence of arrhythmias in the right
      atrium. CONCLUSIONS: BPP from foci outside the regions of dominant activation
      alters dispersion of atrial repolarization. Modulation of apamin-sensitive
      channels may contribute to the shortening of repolarization in CS and PV regions.
      Alterations of atrial repolarization gradient create an arrhythmogenic substrate
      and may be an early step in atrial electrophysiologic remodeling.

PMID- 15950207
TI  - Shared circulation in parabiosis leads to the transfer of bone phenotype from gld
      to the wild-type mice.
AB  - We have previously shown that mice with generalised lymphoproliferative disorder
      (gld) have increased bone mass in addition to autoimmune disease characterised by
      the accumulation of double negative (dn) T lymphocytes (CD3(+)CD4(-)CD8(
      )CD45R(+)). To further explore the association of the immune disorder with the
      bone phenotype of gld mice, we established parabiotic circulation between gld and
      wild-type animals (C57BL/6, B6). One week after the surgery, the proportion of dn
      T lymphocytes increased in peripheral blood, bone marrow, spleen, and lymph nodes
      of wild-type members of the B6-gld parabiotic pair and decreased in tissues of
      gld pair members. The mixing of cells continued during four weeks of parabiosis.
      Number of osteoclast-like (OCL) cells in bone marrow cultures from a wild-type
      member of B6-gld parabiotic pair at the end of the first week decreased from
      266+/-52 to 120+/-5OCL/cm(2), P<0.05, comparable with gld mice (99+/
      21OCL/cm(2)), while the number of osteoblast colonies did not change. After four
      weeks, number of OCL cells formed from the bone marrow of B6 parabiotic mice was
      still similar to the number of OCL cells in their gld counterparts (150+/-18 and
      131+/-24OCL/cm(2), respectively). In addition, the number of osteoblast colonies
      in B6 members of B6-gld parabiotic pairs increased (from 6+/-2 to 18+/
      1colonies/cm(2), P<0.05) thus resembling the cell cultures of gld mice (18+/
      1colonies/cm(2)). Taken together, these data show that the circulation of cells,
      including dn T lymphocytes established by parabiosis confers the osteoclast and
      osteoblast phenotype of gld to wild-type animals.

PMID- 15950209
TI  - Phase I and II metabolism and carbohydrate metabolism in cultured cryopreserved
      porcine hepatocytes.
AB  - Primary porcine hepatocytes were cryopreserved using freezing boxes or a
      programmable freezer (PF). Upon thawing and culturing in 12-well plates
      cryopreserved hepatocytes were compared with their fresh controls on days 1 and 2
      after plating. Cryopreserved hepatocytes attached approximately as well as fresh
      hepatocytes and useful cultures were obtained. In cryopreserved hepatocytes,
      coumarin 7-hydroxylation, 6beta-testosterone hydroxylation and p-nitrophenol
      glucuronidation were reduced to about 10-40, 35 and 40%, respectively, compared
      to their fresh counterparts. Glycogen synthesis in cryopreserved hepatocytes was
      reduced to about 30% on day 1 of culture and about 47% on day 2 of culture
      compared to the synthesis in fresh hepatocytes. Both fresh and cryopreserved
      hepatocytes increased the synthesis by twofold in response to stimulation with
      insulin. Reduced basal levels of glycogen and of glycogen synthesis could be
      explained by an increased energy demand in cryopreserved hepatocytes needing to
      repair damages caused by cryopreservation. Glycogenolysis was reduced to about
      50% in cryopreserved hepatocytes and gluconeogenesis to about 40% of the glucose
      production in fresh hepatocytes. In both fresh and cryopreserved hepatocytes the
      glucose production from glycogenolysis and gluconeogenesis, respectively, was
      increased fourfold in response to stimulation with glucagon. Overall, the
      hepatocytes cryopreserved in boxes had a tendency to perform better than
      hepatocytes cryopreserved in a programmable freezer. In conclusion, the
      cryopreserved hepatocytes were metabolic active; however, to a lower extent than
      the fresh hepatocytes, although, the cryopreserved hepatocytes responded as well
      as the fresh hepatocytes to insulin and glucagon.

PMID- 15950210
TI  - The interactions of 9,10-phenanthrenequinone with glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), a potential site for toxic actions.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the oxidative
      phosphorylation of glyceraldehyde 3-phosphate to 1,3-diphosphoglycerate, one of
      the precursors for glycolytic ATP biosynthesis. The enzyme contains an active
      site cysteine thiolate, which is critical for its catalytic function. As part of
      a continuing study of the interactions of quinones with biological systems, we
      have examined the susceptibility of GAPDH to inactivation by 9,10
      phenanthrenequinone (9,10-PQ). In a previous study of quinone toxicity, this
      quinone, whose actions have been exclusively attributed to reactive oxygen
      species (ROS) generation, caused a reduction in the glycolytic activity of GAPDH
      under aerobic and anaerobic conditions, indicating indirect and possible direct
      actions on this enzyme. In this study, the effects of 9,10-PQ on GAPDH were
      examined in detail under aerobic and anaerobic conditions so that the role of
      oxygen could be distinguished from the direct effects of the quinone. The results
      indicate that, in the presence of the reducing agent DTT, GAPDH inhibition by
      9,10-PQ under aerobic conditions was mostly indirect and comparable to the direct
      actions of exogenously-added H2O2 on this enzyme. GAPDH was also inhibited by
      9,10-PQ anaerobically, but in a somewhat more complex manner. This quinone, which
      is not considered an electrophile, inhibited GAPDH in a time-dependent manner,
      consistent with irreversible modification and comparable to the electrophilic
      actions of 1,4-benzoquinone (1,4-BQ). Analysis of the anaerobic inactivation
      kinetics for the two quinones revealed comparable inactivation rate constants
      (k(inac)), but a much lower inhibitor binding constant (K(i)) for 1,4-BQ.
      Protection and thiol titration studies suggest that these quinones bind to the
      NAD+ binding site and modify the catalytic thiol from this site. Thus, 9,10-PQ
      inhibits GAPDH by two distinct mechanisms: through ROS generation that results in
      the oxidization of GAPDH thiols, and by an oxygen-independent mechanism that
      results in the modification of GAPDH catalytic thiols.

PMID- 15950211
TI  - Hydration properties of N-(alpha-hydroxyacyl)-sphingosine: X-ray powder
      diffraction and FT-Raman spectroscopic studies.
AB  - The thermotropic properties of N-(alpha-hydroxyacyl)-sphingosine (CER[AS]) in dry
      and hydrated state were studied by means of X-ray powder diffraction and FT-Raman
      spectroscopy. The polymorphic states of the CER[AS]/water mixture (lamellar
      crystalline, lamellar hexagonal gel, liquid crystalline) depend on the thermal
      pre-treatment of the sample. Only by heating the CER[AS]/water mixture above the
      melting chain transition can the system be hydrated. At room temperature, both
      dry and hydrated states form lamellar structures, which differ in their repeat
      distance and packing of hydrocarbon chains. Above the melting chain transition,
      hydrated CER[AS] forms a liquid crystalline hexagonal phase, whereas anhydrous
      CER[AS] forms an isotropic liquid phase. The various phases of hydrated CER[AS]
      are distinguished on the basis of the corresponding Raman spectra.

PMID- 15950212
TI  - Clinical enzymology: an autobiographical history.
AB  - In this paper, I review the origins of Clinical Enzymology with special emphasis
      on the years between 1960 and 1980 when the greatest advances in the subject took
      place. These are described in relation to my own research interests and
      contributions, focusing upon subclinical hepatic damage caused by viral infection
      and by alcohol; myocardial infarction; detection of cervical carcinoma by vaginal
      fluid analysis; evaluation of pancreatic function; and the clinical implications
      of microsomal enzyme induction. Reasons are proposed for the failure of
      enzymology to attain the status of an autonomous medical specialty, in contrast
      to the success of similar fields of knowledge that grew up in the same era.

PMID- 15950213
TI  - Ablation of the secondary heart field leads to tetralogy of Fallot and pulmonary
      atresia.
AB  - Recent studies in chick and mouse embryos have identified a previously
      unrecognized secondary heart field (SHF), located in the ventral midline
      splanchnic mesenchyme, which provides additional myocardial cells to the outflow
      tract as the heart tube lengthens during cardiac looping. In order to further
      delineate the contribution of this secondary myocardium to outflow development,
      we labeled the right SHF of Hamburger-Hamilton (HH) stage 14 chick embryos via
      microinjection of DiI/rhodamine and followed the fluorescently labeled cells over
      a 96-h time period. These experiments confirmed the movement of the SHF into the
      outflow and its spiraling migration distally, with the right side of the SHF
      contributing to the left side of the outflow. In contrast, when the right SHF was
      labeled at HH18, the fluorescence was limited to the caudal wall of the
      lengthening aortic sac. We then injected a combination of DiI and neutral red
      dye, and ablated the SHF in HH14 or 18 chick embryos. Embryos were allowed to
      develop until day 9, and harvested for assessment of outflow alignment. Of the
      embryos ablated at HH14, 76% demonstrated cardiac defects including overriding
      aorta and pulmonary atresia, while none of the sham-operated controls were
      affected. In addition, the more severely affected embryos demonstrated coronary
      artery anomalies. The embryos ablated at HH18 also manifested coronary artery
      anomalies but maintained normal outflow alignment. Therefore, the myocardium
      added to the outflow by the SHF at earlier stages is required for the elongation
      and appropriate alignment of the outflow tract. However, at later stages, the SHF
      contributes to the smooth muscle component of the outflow vessels above the
      pulmonary and aortic valves which is important for the development of the
      coronary artery stems. This work suggests a role for the SHF in a subset of
      congenital heart defects that have overriding aorta and coronary artery
      anomalies, such as tetralogy of Fallot and double outlet right ventricle.

PMID- 15950214
TI  - Analysis of tissue flow patterns during primitive streak formation in the chick
      embryo.
AB  - We have investigated the patterns of tissue flow underlying the formation of the
      primitive streak in the chick embryo. Analysis of time-lapse sequences of
      brightfield images to extract the tissue velocity field and of fluorescence
      images of small groups of DiI-labelled cells have shown that epiblast cells move
      in two large-scale counter-rotating streams, which merge at the site of streak
      formation. Despite the large-scale tissue flows, individual cells appear to move
      little relative to their neighbours. As the streak forms, it elongates in both
      the anterior and posterior directions. Inhibition of actin polymerisation via
      local application of the inhibitor latrunculin A immediately terminates anterior
      extension of the streak tip, but does not prevent posterior elongation.
      Inhibition of actin polymerisation at the base of the streak completely inhibits
      streak formation, implying that continuous movement of cells into the base of the
      forming streak is crucial for extension. Analysis of cycling cells in the early
      embryo shows that cell-cycle progression in the epiblast is quite uniform before
      the primitive streak forms then decreases in the central epiblast and incipient
      streak and increases at the boundary between the area pellucida and area opaca
      during elongation. The cell-cycle inhibitor aphidicolin, at concentrations that
      completely block cell-cycle progression, permits initial streak formation but
      arrests development during extension. Our analysis suggests that cell division
      maintains the cell-flow pattern that supplies the streak with cells from the
      lateral epiblast, which is critical for epiblast expansion in peripheral areas,
      but that division does not drive streak formation or the observed tissue flow.

PMID- 15950215
TI  - Prospective isolation of late development multipotent precursors whose migration
      is promoted by EGFR.
AB  - A simple procedure to isolate neural stem cells would greatly facilitate direct
      studies of their properties. Here, we exploited the increase in EGF receptor
      (EGFR) levels, that occurs in late development stem cells or in younger
      precursors upon exposure to FGF-2, to isolate cells expressing high levels of
      EGFR (EGFR(high)) from the developing and the adult brain. Independently of age
      and region of isolation, EGFR(high) cells were highly enriched in multipotent
      precursors and displayed similar antigenic characteristics, with the exception of
      GFAP and Lex/SSEA-1 that were mainly expressed in adult EGFR(high) cells. EGFR
      levels did not correlate with neurogenic potential, indicating that the increase
      in EGFR expression does not directly affect differentiation. Instead, in the
      brain, many EGFR(high) precursors showed tangential orientation and, whether
      isolated from the cortex or striatum, EGFR(high) precursors displayed
      characteristics of cells originating from the ventral GZ such as expression Dlx
      and Mash-1 and the ability to generate GABAergic neurons and oligodendrocytes.
      Moreover, migration of EGFR(high) cells on telencephalic slices required EGFR
      activity. Thus, the developmentally regulated increase in EGFR levels may affect
      tangential migration of multipotent precursors. In addition, it can be used as a
      marker to effectively isolate telencephalic multipotent precursors from embryonic
      and adult tissue.

PMID- 15950216
TI  - NETRIN and SLIT guide salivary gland migration.
AB  - Directed migration is pivotal for the proper placement and function of nearly all
      organs. The majority of known guidance molecules involved in directed migration
      have been identified from studies of migrating axons during nervous system
      development. Here, we show that at least two of these axon guidance molecules,
      NETRIN and SLIT, act through their canonical receptors, to guide Drosophila
      embryonic salivary glands. NETRIN serves as a chemo-attractant while SLIT
      functions antagonistically to NETRIN as a chemo-repellent during salivary gland
      migration. CNS midline expression of both NETRIN and SLIT directs the glands to
      move unswervingly parallel to the CNS. NETRIN expression is also required in the
      visceral mesoderm, along which the glands move during their migration. We propose
      that analogous to axon guidance, a balance between chemo-attractants and chemo
      repellents is required for the proper migratory path of the developing salivary
      glands.

PMID- 15950217
TI  - c-Jun controls the efficiency of MAP kinase signaling by transcriptional
      repression of MAP kinase phosphatases.
AB  - The mammalian JNK signaling pathway regulates the transcriptional response of
      cells to environmental stress, including UV irradiation. This signaling pathway
      is composed of a classical MAP kinase cascade; activation results in
      phosphorylation of the transcription factor substrates c-Jun and ATF2, and leads
      to changes in gene expression. The defining components of this pathway are
      conserved in the fission yeast S. pombe, where the genetic studies have shown
      that the ability of the JNK homolog Spc1 to be activated in response to UV
      irradiation is dependent on the presence of the transcription factor substrate
      Atf1. We have used genetic analysis to define the role of c-Jun in activation of
      the mammalian JNK signaling pathway. Our results show that optimal activation of
      JNK requires the presence of its transcription factor substrate c-Jun. Mutational
      analysis shows that the ability of c-Jun to support efficient activation of JNK
      requires the ability of Jun to bind DNA, suggesting a transcriptional mechanism.
      Consistent with this, we show that c-Jun represses the expression of several MAP
      kinase phosphatases. In the absence of c-Jun, the increased expression of MAP
      kinase phosphatases leads to impaired activation of the ERK, JNK, and p38 MAP
      kinases after pathway activation. The results show that one function of c-Jun is
      to regulate the efficiency of signaling by the ERK, p38, and JNK MAP kinases, a
      function that is likely to affect cellular responses to many different stimuli.

PMID- 15950219
TI  - Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in
      vivo.
AB  - The aim of the present study was to investigate the efficacy of fucoxanthin on
      endotoxin-induced uveitis (EIU) in rats. The effects of fucoxanthin on endotoxin
      induced leucocyte and protein infiltration, nitric oxide (NO), prostaglandin (PG)
      E2 and tumour necrosis factor (TNF)-alpha concentrations in rat aqueous humour,
      as well as on the cyclooxygenase (COX)-2 and inducible nitric oxide synthase
      (iNOS) protein expression in a mouse macrophage cell line (RAW 264.7 cells) were
      studied. EIU was induced in male Lewis rats by a footpad injection of
      lipopolysaccharide (LPS). Immediately after the LPS injection, either 0.1, 1 or
      10mgkg(-1) of fucoxanthin was injected intravenously. The aqueous humour was
      collected 24hr later from both eyes, and both the number of cells infiltrating
      into the aqueous humour and the aqueous humour protein concentration were
      measured. The levels of PGE2, NO and TNF-alpha were determined by enzyme-linked
      immunosorbent assay. The RAW 264.7 cells were pretreated with various
      concentrations of fucoxanthin for 24hr and subsequently incubated with LPS for
      24hr. COX-2 and iNOS protein expression was analysed by the Western blotting
      method. Levels of PGE2, NO and TNF-alpha production were determined. Fucoxanthin
      suppressed the development of EIU in a dose-dependent fashion. Treatment with
      fucoxanthin resulted in a reduction in PGE2, NO and TNF-alpha concentrations in
      the aqueous humour. The expression of COX and iNOS protein in the fucoxanthin
      treated RAW264.7 cells decreased significantly compared to that the LPS group. It
      also significantly reduced the concentration of PGE2, NO and TNF-alpha production
      in the medium of cells. The present result indicate fucoxanthin suppresses the
      inflammation of EIU by blocking the iNOS and COX-2 protein expression and its
      anti-inflammatory effect on eye is comparable with the effect of predinisolone
      used in similar doses.

PMID- 15950220
TI  - Effects of SOV-induced phosphatase inhibition and expression of protein tyrosine
      phosphatases in rat corneal endothelial cells.
AB  - Contact inhibition is an important mechanism for maintaining corneal endothelium
      in a non-replicative state. Protein tyrosine phosphatases (PTPs) play a role in
      regulating the integrity of cell-cell contacts, differentiation, and growth. In
      this study, we aimed to evaluate whether phosphatases are involved in the
      maintenance of contact-dependent inhibition of proliferation in corneal
      endothelial cells and to identify candidate PTPs that are expressed in these
      cells and might be involved in regulation of contact inhibition. Confluent
      cultures of rat corneal endothelial cells or endothelium in ex vivo corneas were
      treated with the general phosphatase inhibitor, sodium orthovanadate (SOV).
      Immunocytochemistry (ICC) evaluated the effect of SOV on cell-cell contacts by
      staining for ZO-1, and on cell cycle progression by staining for Ki67. Transverse
      sections of rat cornea and cultured rat corneal endothelial cells were used to
      test for expression of the candidate PTPs: PTP-mu, PTP-LAR, PTP1B, SHP-1, SHP-2,
      and PTEN using ICC and either Western blots or RT-PCR. ZO-1 staining demonstrated
      that SOV induced a time-dependent release of cell-cell contacts in confluent
      cultures of corneal endothelial cells and in the endothelium of ex vivo corneas.
      Staining for Ki67 indicated that SOV promoted limited cell cycle progression in
      the absence of serum. PTP-mu, PTP1B, SHP-1, SHP-2, and PTEN, but not PTP-LAR,
      were expressed in rat corneal endothelial cells in situ and in culture. The
      subcellular location of PTP-mu and PTP1B differed in subconfluent and confluent
      cells, while that of SHP-1, SHP-2, and PTEN was similar, regardless of confluent
      status. Western blots confirmed the expression of PTP1B, SHP-1, SHP-2, and PTEN.
      RT-PCR confirmed expression of PTP-mu mRNA. Phosphatases are involved in
      regulation of junctional integrity and of cell proliferation in corneal
      endothelial cells. PTP-mu, PTP1B, SHP-1, SHP-2, and PTEN are expressed in rat
      corneal endothelium and may be involved in regulation of contact inhibition in
      these normally non-proliferating cells.

PMID- 15950218
TI  - Chinese hamster ORC subunits dynamically associate with chromatin throughout the
      cell-cycle.
AB  - In yeast, the Origin Recognition Complex (ORC) is bound to replication origins
      throughout the cell-cycle, but in animal cells, there are conflicting data as to
      whether and when ORC is removed from chromatin. We find ORC1, 2 and ORC4 to be
      metabolically stable proteins that co-fractionate with chromatin throughout the
      cell-cycle in Chinese hamster fibroblasts. Since cellular extraction methods
      cannot directly examine the chromatin binding properties of proteins in vivo, we
      examined ORC:chromatin interactions in living cells. Fluorescence loss in
      photobleaching (FLIP) studies revealed ORC1 and ORC4 to be highly dynamic
      proteins during the cell-cycle with exchange kinetics similar to other regulatory
      chromatin proteins. In vivo interaction with chromatin was not significantly
      altered throughout the cell-cycle, including S-phase. These data support a model
      in which ORC subunits dynamically interact with chromatin throughout the cell
      cycle.

PMID- 15950221
TI  - Unilateral subcutaneous bee venom but not formalin injection causes contralateral
      hypersensitized wind-up and after-discharge of the spinal withdrawal reflex in
      anesthetized spinal rats.
AB  - This study aimed to investigate the effect of tonic nociception on spinal
      withdrawal reflexes including (1) long lasting spontaneous responses elicited by
      subcutaneous (s.c.) administration of formalin (2.5%, 50 microl) and bee venom
      (BV, 0.2 mg/50 microl) into the hind paw and (2) corresponding ipsilateral
      (primary) and contralateral (secondary) hypersensitivity to noxious pinch and
      repetitive supra-threshold (1.5 x T) electrical stimuli at different frequencies
      (3 Hz: wind-up; 20 Hz: after-discharge) in anesthetized spinal rats. Spinal
      withdrawal reflexes were studied by simultaneously assessing single motor units
      (SMUs) electromyographic (EMG) activities from the bilateral medial gastrocnemius
      (MG) muscles. Subcutaneous formalin-induced persistent spontaneous SMU EMG
      responses were in typical biphasic manner with an apparent silent period (about
      13-18 min), but in contrast, BV elicited monophasic long lasting (about 1 h) SMU
      EMG responses without any resting state. The mechanically and electrically evoked
      responsiveness of SMUs were enhanced significantly by ipsilateral BV injection,
      whereas enhanced electrically, but not mechanically, evoked responses (including
      wind-up and after-discharge) were found at the non-injection site of the
      contralateral hind paw. However, s.c. administration of formalin was only able to
      establish ipsilateral hypersensitivity of the SMUs to repeated electrical, not
      mechanical, stimulation. Neither mechanically nor electrically evoked
      contralateral hypersensitivity of the SMUs was found during the ipsilateral
      formalin-induced nociception. For pharmacological intervention, intrathecal
      administration of the non-N-methyl-d-aspartate (non-NMDA) receptor antagonist
      CNQX (40 nmol/10 microl), but not the non-competitive NMDA receptor antagonist MK
      801 (40 nmol/10 microl), significantly depressed BV-induced contralateral
      hypersensitivity of the SMUs to repeated 3 Hz (wind-up) and 20 Hz (after
      discharge) frequencies of electrical stimulation. Using the extracellular SMU
      recording technique, we found that s.c. administration of formalin and BV shows a
      significant difference in long lasting spontaneous firing of SMUs. This is
      consistent with previous observations in animal behavioral studies. Additionally,
      contralateral electrically evoked hypersensitivity of the SMUs was found only
      following BV injection, not in the formalin test. The maintenance and development
      of BV-induced contralateral hypersensitivity of the spinal withdrawal reflex to
      noxious electrical stimulation indeed depend on different central pharmacological
      receptors. The spinal non-NMDA, but not the NMDA, receptors may play important
      role in BV-induced contralateral central hyperexcitability and sensitization.

PMID- 15950222
TI  - Hypoxic preconditioning attenuated in kainic acid-induced neurotoxicity in rat
      hippocampus.
AB  - The neuroprotective effect of hypoxic preconditioning on kainate (KA)-induced
      neurotoxicity, including apoptosis and necrosis, was investigated in rat
      hippocampus. Female Wistar-Kyoto rats were subjected to 380 mm Hg in an altitude
      chamber for 15 h/day for 28 days. Intrahippocampal infusion of KA was performed
      in chloral hydrate anesthetized rats, which acutely elevated 2,3-dihydroxybenzoic
      acid levels in normoxic rats. Seven days after the infusion, KA increased lipid
      peroxidation in the infused hippocampus and resulted in hippocampal CA3 neuronal
      loss. A 4-week hypoxic preconditioning attenuated KA-induced elevation in
      hydroxyl radical formation and lipid peroxidation as well as KA-induced neuronal
      loss. The effects of hypoxic preconditioning on KA-induced apoptosis and necrosis
      were investigated further. Two hours after KA infusion, cytosolic cytochrome c
      content was increased in the infused hippocampus. Twenty-four hours after KA
      infusion, pyknotic nuclei, cellular shrinkage, and cytoplasmic disintegration,
      but not TUNEL-positive staining, were observed in the CA3 region of hippocampus.
      Forty-eight hours after KA infusion, both DNA smear and DNA fragmentation were
      demonstrated in the infused hippocampus. Furthermore, TUNEL-positive cells,
      indicative of apoptosis, in the infused hippocampus were detected 72 h after KA
      infusion. Hypoxic pretreatment significantly reduced necrotic-like events in the
      KA-infused hippocampus. Moreover, hypoxic preconditioning attenuated apoptosis
      induced by KA infusion, including elevation in cytosolic cytochrome c content,
      TUNEL-positive cells, and DNA fragmentation. Our data suggest that hypoxic
      preconditioning may exert its neuroprotection of KA-induced oxidative injuries
      via attenuating both apoptosis and necrosis in rat hippocampus.

PMID- 15950223
TI  - Involvement of circadian clock gene Clock in diabetes-induced circadian
      augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in the mouse
      heart.
AB  - Diabetes is associated with an excess risk of cardiac events, and one of the risk
      factors for infarction is the elevated-levels of plasminogen activator inhibitor
      1 (PAI-1). To evaluate how the molecular clock mechanism is involved in the
      diabetes-induced circadian augmentation of PAI-1 gene expression, we examined the
      expression profiles of PAI-1 mRNA in the hearts of Clock mutant mice with
      streptozotocin-induced diabetes. Circadian expression of PAI-1 mRNA was blunted
      to low levels under both normal and diabetic conditions in Clock mutant mice,
      although the expression rhythm was augmented in diabetic wild-type (WT) mice.
      Furthermore, plasma PAI-1 levels became significantly higher in WT mice than in
      Clock mutant mice after STZ administration. Our results suggested that the
      circadian clock component, CLOCK, is involved in the diabetes-induced circadian
      augmentation of PAI-1 expression in the mouse heart.

PMID- 15950224
TI  - A molecular dynamics study of human serum albumin binding sites.
AB  - A 2.0 ns unrestrained Molecular Dynamics was used to elucidate the geometric and
      dynamic properties of the HSA binding sites. The structure is not stress affected
      and the rmsds calculated from the published crystallographic data are almost
      constant for all the simulation time, with an averaged value of 2.4A. The major
      variability is in the C-terminus region. The trajectory analysis of the IIA
      binding site put in evidence fast oscillations for the
      Cgamma@Leu203...Cgamma@Leu275 and Cgamma@Leu219...Cgamma@Leu260 distances, with
      fluctuations around 250 ps, 1000 ps and over for the first, while the second is
      smoothly increasing with the simulation time from 7 to 10A. These variations are
      consistent with a volume increase up to 20% confirmed by the inter-domain
      contacts analysis, in particular for the pair O@Pro148...Ogamma@Ser283,
      representing the change of distance between IB-h9 and IIA-h6,
      O@Glu149...Ogamma@Ser189 for sub-domains IB-h9/IIA-h1 and
      N@Val339...Odelta2@Asp447 sub-domains IIB-h9/IIIA-h1. These inter-domain motions
      confirm the flexibility of the unfatted HSA with possible binding site pre
      formation.

PMID- 15950225
TI  - Synthesis and structural characterization of derivatives of 2- and 3
      benzo[b]furan carboxylic acids with potential cytotoxic activity.
AB  - Derivatives of 2- and 3-benzo[b]furancarboxylic acids were prepared and evaluated
      for their cytotoxic potential in the National Cancer Institute, Bethesda, USA.
      Six compounds: 7-acetyl-6-hydroxy-3-methyl-2-benzofurancarboxylic acid (2), 6
      hydroxy-7-(p-methoxycinnamoyl)-3-methyl-2-benzofurancarboxylic acid (4), 5-bromo
      7-hydroxy-6-methoxy-2-benzofurancarboxylic acid methyl ester (6a), 6-acetyl-5-(O
      ethyl-2'-diethylamino)-2-methyl-3-benzofurancarboxylic acid methyl ester (1f), 6
      (O-ethyl-2'-diethylamino)-7-p-methoxycinnamoyl)-3-methyl-2-benzofurancarboxylic
      acid methyl ester hydrochloride (4b), 5-bromo-7-(O-ethyl-2'-diethylamino)-6
      methoxy-2-benzofurancarboxylic acid methyl ester (6b) showed significant
      cytotoxic activities against human cancer cell lines. In addition the crystal
      structures of 7-methoxy-2-benzofurancarboxylic acid methyl ester (7a) has been
      solved by X-ray structure analysis of single crystals.

PMID- 15950226
TI  - Adsorptive stripping voltammetric determination of triprolidine hydrochloride in
      pharmaceutical tablets.
AB  - The electrochemical behavior of antihistaminic drug, viz. triprolidine
      hydrochloride (TripCl), at a hanging mercury drop electrode (HMDE) is
      investigated. Chemical and electrical parameters affecting the adsorptive
      voltammetric measurements are optimized. Different modes of sweep, viz. direct
      current DC, normal pulse NP, differential pulse DP and square wave SW modes, over
      the potential range from -800 to -1400 mV, are used in the presence of 0.04 M
      Britton-Robinson buffer pH 11, with accumulation time 30 s, scan rate 50 mV/s and
      pulse amplitude 50 mV. The reduction process is irreversible and involved the
      transfer of two electrons and two protons. Their responses are linear over the
      concentration range 15-157 ng/ml with average correlation coefficient 0.9998,
      while the detection limit is 2.64, 6.24, 8.80 and 2.12 ng/ml for DC, DP, SW and
      NP mode, respectively. The differential pulse method has been applied
      successfully for the determination of the drug in Egyptian pharmaceutical
      preparation with mean recovery 99.55+/-0.67%.

PMID- 15950227
TI  - Synthesis and antibacterial activity of 1H-pyrazolo[3,4-b]pyrazine and -pyridine
      derivatives.
AB  - The investigations of new pyrazine and pyridine derivatives showing an
      antibacterial activity have been made. Upon treatment of 3-chloro-2-cyanopyrazine
      [1] and 2-chloro-3-cyanopyridine with 1,1-dimethyl-hydrazine, 1-aminopiperidine
      and 1-amino-4-methylpiperazine, either the pyrazolo-pyrazine (1), and -pyridine
      (2) derivatives, or ammonium salts (3-8) were obtained, according to the reaction
      conditions. Compound 1 was obtained in the reaction of the initial nitrile with
      methylhydrazine as well. The reactions of 1 gave the following derivatives:
      acylation-(9), that with p-chlorobenzoic aldehyde-(10), and with phenyl
      isothiocyanate-(11). 3-Chloro-2-cyanopyrazine treated with hydrazine hydrate gave
      amidrazone (12), which upon condensation with p-chlorobenzoic aldehyde produced
      (13). The compounds obtained were tested in vitro for their tuberculostatic
      activity. The minimal inhibitory concentration (MIC) values were within 22-100
      microg/cm3. Compounds 1, 5 and 6 were also tested in vitro for their activity
      towards 25 strains of anaerobic, and 25 strains of aerobic bacteria. They
      appeared to be of elevated activity towards the anaerobes and of low one towards
      the aerobes (Table 2).

PMID- 15950229
TI  - In vivo imaging of tissue eosinophilia and eosinopoietic responses to schistosome
      worms and eggs.
AB  - Using a sensitive transgenic reporter mouse system and in vivo biophotonic
      imaging techniques, we present a dynamic analysis of eosinophil responses to
      schistosome infection. Use of this methodology provided previously unattainable
      detail on the spatial and temporal distribution of tissue eosinophilia and
      eosinopoietic responses to schistosome worms and eggs. Dramatic hepatic and
      intestinal eosinophilia in response to the deposition of schistosome eggs, with
      accompanying eosinopoiesis in the bone marrow, was observed between weeks 8 and
      10 p.i., with subsequent downregulation evident by week 11. Contrary to
      expectations, we also demonstrate that schistosome parasites themselves induce
      significant intestinal eosinophilia and eosinopoiesis in the bone marrow at very
      early stages during prepatent infection.

PMID- 15950230
TI  - Multiple cathepsin B isoforms in schistosomula of Trichobilharzia regenti:
      identification, characterisation and putative role in migration and nutrition.
AB  - Among schistosomatids, Trichobilharzia regenti, displays an unusual migration
      through the peripheral and central nervous system prior to residence in the nasal
      cavity of the definitive avian host. Migration causes tissue degradation and
      neuromotor dysfunction both in birds and experimentally infected mice. Although
      schistosomula have a well-developed gut, the peptidases elaborated that might
      facilitate nutrition and migration are unknown. This is, in large part, due to
      the difficulty in isolating large numbers of migrating larvae. We have identified
      and characterised the major 33 kDa cathepsin B-like cysteine endopeptidase in
      extracts of migrating schistosomula using fluorogenic peptidyl substrates with
      high extinction coefficients and irreversible affinity-labels. From first strand
      schistosomula cDNA, degenerate PCR and Rapid Amplification of cDNA End protocols
      were used to identify peptidase isoforms termed TrCB1.1-TrCB1.6. Highest sequence
      homology is to the described Schistosoma mansoni and Schistosoma japonicum
      cathepsins B1. Two isoforms (TrCB1.5 and 1.6) encode putatively inactive enzymes
      as the catalytic cysteine is substituted by glycine. Two other isoforms, TrCB1.1
      and 1.4, were functionally expressed as zymogens in Pichia pastoris. Specific
      polyclonal antibodies localised the peptidases exclusively in the gut of
      schistosomula and reacted with a 33kDa protein in worm extracts. TrCB1.1 zymogen
      was unable to catalyse its own activation, but was trans-processed and activated
      by S. mansoni asparaginyl endopeptidase (SmAE aka. S. mansoni legumain). In
      contrast, TrCB1.4 zymogen auto-activated, but was resistant to the action of
      SmAE. Both activated isoforms displayed different pH-dependent specificity
      profiles with peptidyl substrates. Also, both isoforms degraded myelin basic
      protein, the major protein component of nervous tissue, but were inefficient
      against hemoglobin, thus supporting the adaptation of T. regenti gut peptidases
      to parasitism of host nervous tissue.

PMID- 15950231
TI  - Eosinophilic infiltration in restenotic tissue following coronary stent
      implantation.
AB  - OBJECTIVES: The aim of our study was to compare the histopathological features of
      restenotic tissue after balloon angioplasty and after stent placement. We
      emphasized on specific types of inflammatory cells to evaluate the type of tissue
      immune response in both situations. METHODS: A total of 32 patients underwent
      elective directional coronary atherectomy; 16 patients had restenosis after
      balloon angioplasty, 16 patients had in-stent restenosis (ISR). Atherectomy
      specimens were stained with antibodies against T cells, eosinophils, smooth
      muscle cell actin, macrophages and with antibodies against T cell activation
      markers. Quantitative morphometric analysis was performed using image analysis
      software. RESULTS: In-stent restenotic tissue contained more smooth muscle cells
      (P < 0.001), anti-CD3 positive T cells (P < 0.001) and eosinophils (P = 0.012).
      Anti-CD40L positive activated T cells were more numerous in ISR lesions (P =
      0.003) and were frequently clustered around stent imprints in the tissue. Five
      ISR specimens contained grossly visible stent fragments amidst the restenotic
      tissue. In all cases of balloon restenosis, T cells and eosinophils (if present)
      were concentrated around lipid rich tissue. CONCLUSIONS: Our study indicates
      involvement of inflammatory responses in both types of restenosis, with
      significantly more eosinophils encountered in case of in-stent restenosis. In
      contrast with clustering of inflammatory cells around stent struts after stent
      placement, the inflammatory cells in balloon restenosis were located in
      association with lipid rich tissue, suggesting different inflammatory triggers in
      balloon restenosis and in-stent restenosis.

PMID- 15950232
TI  - S18886, a selective TP receptor antagonist, inhibits development of
      atherosclerosis in rabbits.
AB  - OBJECTIVE: To investigate the effect of S18886, a novel TP (thromboxane A2 and
      prostaglandin endoperoxide) receptor antagonist, on the development of aortic
      fatty streaks and advanced lesions in a rabbit model of atherosclerosis and
      restenosis. METHODS AND RESULTS: The right iliac artery of 96 rabbits (8 groups,
      n=12/group) was balloon injured, then the animals were fed a cholesterol-enriched
      diet for 6 weeks. In Groups 1-4, concomitant oral administration of S18886 at 5
      mg/kg/day over the 6-week-period reduced the intima to media ratio of lesions in
      the uninjured aorta and injured iliac artery, the accumulation of macrophages and
      the expression of ICAM-1 compared with 1 mg/kg/day S18886, 30 mg/kg/day aspirin
      and placebo, with no effect on body weight or plasma cholesterol levels. In
      Groups 5-8, 2 weeks of treatment with 5 mg/kg/day S18886 reduced the intima to
      media ratio of restenosing lesions when pre-formed iliac artery lesions underwent
      a second balloon injury at week 6. The smaller lesions resulting from S18886
      treatment correlated with a significant decrease in the neointimal area occupied
      by macrophages, as well as in ICAM-1 expression, with no effect on the smooth
      muscle component. Aspirin treatment had no significant effect on the neointimal
      smooth muscle component, but partially inhibited macrophage infiltration, without
      inhibiting ICAM-1 expression. CONCLUSION: Inhibition of the TP receptor using
      S18886 causes a significant decrease in the recruitment of monocyte/macrophages
      within fatty streaks in the uninjured aorta and within primary and restenosing
      atherosclerotic lesions in the iliac artery of rabbits. Since TP receptor
      agonists, such as thromboxane A2, prostanoid endoperoxides and isoprostanes
      participate in vessel wall inflammation and are localized and increased in
      atherosclerotic plaques, treatment with S18886 may enhance atherosclerotic lesion
      stability by attenuating inflammatory processes that ultimately lead to plaque
      rupture.

PMID- 15950233
TI  - Degeneration affects the fiber reorientation of human annulus fibrosus under
      tensile load.
AB  - The angled, lamellar structure of the annulus fibrosus is integral to its load
      bearing function. Reorientation of this fiber structure with applied load may
      contribute to nonlinear mechanical behavior and to large increases in tensile
      modulus. Fiber reorientation has not yet been quantified for loaded non
      degenerated and degenerated annulus fibrosus tissue. The objective of this study
      was to measure fiber reorientation and mechanical properties (toe- and linear
      region modulus, transition strain, and Poisson's ratio) of loaded outer annulus
      fibrosus tissue using a new application of FFT image processing techniques. This
      method was validated for quantification of annulus fiber reorientation during
      loading in this study. We hypothesized that annulus fibrosus fibers would
      reorient under circumferential tensile load, and that fiber reorientation would
      be affine. Additionally, we hypothesized that degeneration would affect fiber
      reorientation, toe-region modulus and Poisson's ratio. Annulus fibrosus fibers
      were found to reorient toward the loading direction, and degeneration
      significantly decreased fiber reorientation (the fiber reorientation parameter,
      m(FFT)=-1.70 degrees /% strain for non-degenerated and -0.95 degrees /% strain
      for degenerated tissue). Toe-region modulus was significantly correlated with age
      (r=0.6). Paired t-tests showed no significant difference in the fiber
      reorientation parameter calculated experimentally with that calculated using an
      affine prediction. Thus, an affine prediction is a good approximation of fiber
      reorientation. The findings of this study add to the understanding of overall
      disc mechanical behavior and degeneration.

PMID- 15950234
TI  - Can initial and additional compensatory steps be predicted in young, older, and
      balance-impaired older females in response to anterior and posterior waist pulls
      while standing?
AB  - The initiation of a single compensatory step in response to balance perturbations
      has been predicted with accuracies of up to 71%. We sought to determine whether
      similar methods also could be used to predict the onset of additional
      compensatory steps in both healthy and balance-impaired older females. Anterior
      and posterior waist pulls of five different magnitudes were applied to 13
      unimpaired young (mean age 23 years), 12 unimpaired older (mean age 71 years),
      and 15 balance-impaired older (mean age 76 years) women. Body segment kinematic
      data were recorded at 100 Hz. A step was predicted when the time for the center
      of-mass to reach the vertical projection of the boundary of the base-of-support
      fell below a certain threshold. The results show that 83% of all steps and non
      steps were correctly predicted at an optimal time-to-boundary threshold
      (tau(opt)) of 0.78 s. Step prediction accuracy did not differ significantly by
      group: 86% of steps and non-steps by young, 84% by unimpaired old, and 82% by
      balance-impaired old women were correctly predicted at tau(opt) of 0.58, 0.67,
      and 0.78 s, respectively. Anterior steps and non-steps were predicted more
      accurately than posterior ones (94% vs. 79% correct at tau(opt) of 0.52 and 0.84
      s, respectively) and initial steps were better predicted than additional ones
      (87% vs. 81% correct at tau(opt) of 0.77 and 0.34 s, respectively). We conclude
      that this step prediction method reasonably predicts initial and additional steps
      in the anterior and posterior direction by all three subject cohorts.

PMID- 15950235
TI  - Molecular interaction in binary surfactant mixtures containing alkyl
      polyglycoside.
AB  - Surface tensions were measured for several binary mixtures of a multidegree
      polymerized alkyl polyglycoside, C12G1.46' with different types of surfactants in
      0.1 M NaCl at 25 degrees C. Based on regular solution theory, using a dimensional
      crystal model and a phase separation model, the molecule exchange energy in mixed
      monolayer formation (epsilon) and mixed micellization (epsilon(m)) were
      determined. Surfactants used in the mixtures with C12G1.46 in this study are
      C12E3S (trioxyethylenated dodecyl sulfonate), C12TAC (dodecyl trimethylammonium
      chloride), BE-6 (hexaoxyethylenated trisiloxane surfactant), and TMN-6
      (hexaoxyethylenated-2,6,8-trimethylnonanol). The mixtures show exchange energy in
      mixed monolayer formation (epsilon) and mixed micellization (epsilon(m)) ranging
      from -660 to -1410 J/mol, indicating a decrease in surface energy upon mixing.
      The decreases in surface energy are in the order C12G1.46/C12E3S >
      C12G1.46/C12TAC, C12G1.46/C12TAC > C12G2/C12TAC and C12G1.46/BE-6 > C12G1.46/TMN
      6. The ability of the mixed monolayer formation relative to the mixed micelle
      formation of the same binary mixture, measured by the (epsilon-epsilon(m))
      values, is in the order C12G1.46/BE-6 > C12G1.46/TMN-6 > C12G1.46/C12E3S-->0 >
      C12G1.46/C12TAC.

PMID- 15950236
TI  - Cuticular hydrocarbon profiles and aggregation in four Periplaneta species
      (Insecta: Dictyoptera).
AB  - Cuticular hydrocarbon (CH) profiles of four Periplaneta species were compared and
      their role in aggregation and interspecific recognition was evaluated. CH
      profiles are species specific and include from 19 to 25 hydrocarbons. P. brunnea,
      P. fuliginosa and P. australasiae have more CH components in common with one
      another than with P. americana. P. americana hydrocarbons include components from
      24 to 43 carbon atoms but hydrocarbons for the three other species range from 21
      to 41 atoms. The major compound in CH profiles in P. americana is 6,9
      heptacosadiene that is absent from the three other species. The major compound in
      CH profiles of P. Brunnea and P. fuliginosa is 13-methyl pentacosane that is not
      found in the CH profile of P. americana. Major compounds in P. australasiae
      species are tricosene and 13-methyl pentacosane, respectively, in males and
      females. Binary choice tests demonstrated that specific CH extracts induced
      aggregation in the four species. High CH amounts were required to induce
      aggregation of P. americana and P. brunnea on conditioned sites, whereas low
      amounts were sufficient to induce aggregation of P. fuliginosa and P.
      australasiae. These results suggest that CHs are involved in aggregation and
      interspecific recognition.

PMID- 15950237
TI  - Repeated plasticization and recovery of cuticular stiffness in the blood-sucking
      bug Triatoma infestans in the feeding context.
AB  - Triatominae bugs experience changes in the mechanical properties of their cuticle
      prior to feeding. This process-plasticization-allows a rapid stretching of the
      unsclerotized abdominal cuticle of triatominae larvae and it is evoked by sensory
      inputs related to feeding. We tested: (a) whether the cuticle recovers its
      original mechanical properties after plasticization, (b) whether repeated
      stimulation would be able to evoke recurrent plasticization along the same larval
      instar, (c) the temporal course of recovering cuticular stiffness. We injected
      Ringer solution into the body cavity of the bugs at constant pressure, using the
      injection rate (ml/min) as a measure of the cuticle extensibility. To trigger
      plasticization, individuals were allowed to feed on blood from an artificial
      feeder at 32+/-2 degrees C. After plasticization occurred, the abdominal cuticle
      gradually recovered its original mechanical properties. Bugs were capable of
      plasticizing for a second time when repeatedly stimulated. The effects of
      plasticization vanished between 1 and 2 h after stimulation. Although one full
      meal could suffice to accomplish moult in other Triatomine species, Triatoma
      infestans is able to feed repeatedly during a single larval instar. Accordingly
      to this, their cuticle recovers stiffness in some hours and becomes able to
      respond repeatedly to sensory inputs associated with feeding.

PMID- 15950238
TI  - Mitotic arrest and toxicity in Biomphalaria glabrata (Mollusca: Pulmonata)
      exposed to colchicine.
AB  - Continuous exposure of Biomphalaria glabrata snails to 0.1% colchicine resulted
      in a significant increase, relative to non-exposed snails, in the number of
      arrested mitotic figures in the amebocyte-producing organ (APO) as soon as 4 h,
      with peak numbers after 12 h of exposure. The number of circulating hemocytes was
      significantly elevated at 24 h. However, by 72 h both the number of mitotic
      figures in the APO and the concentration of circulating hemocytes in the
      hemolymph had returned to control levels. Hemocytes appeared to possess normal
      morphology throughout this exposure, including the formation of long filopodia
      with supporting rodlike structures that have been reported to contain
      microtubules. Snail survival decreased as a function of exposure time.
      Significantly fewer snails, relative to controls, survived a 48-h exposure, and
      only 1 out of 30 snails recovered from a 72-h exposure to 0.1% colchicine.
      Colchicine-exposed snails displayed intoxicated behavior, even upon removal from
      the colchicine solution, although no histopathology was evident in the CNS of
      snails exposed for 72 h.

PMID- 15950239
TI  - Mechanochemistry of t7 DNA helicase.
AB  - The bacteriophage T7 helicase is a ring-shaped hexameric motor protein that
      unwinds double-stranded DNA during DNA replication and recombination. To
      accomplish this it couples energy from the nucleotide hydrolysis cycle to
      translocate along one of the DNA strands. Here, we combine computational biology
      with new biochemical measurements to infer the following properties of the T7
      helicase: (1) all hexameric subunits are catalytic; (2) the mechanical movement
      along the DNA strand is driven by the binding transition of nucleotide into the
      catalytic site; (3) hydrolysis is coordinated between adjacent subunits that bind
      DNA; (4) the hydrolysis step changes the affinity of a subunit for DNA allowing
      passage of DNA from one subunit to the next. We construct a numerical
      optimization scheme to analyze transient and steady-state biochemical
      measurements to determine the rate constants for the hydrolysis cycle and
      determine the flux distribution through the reaction network. We find that, under
      physiological and experimental conditions, there is no dominant pathway; rather
      there is a distribution of pathways that varies with the ambient conditions. Our
      analysis methods provide a systematic procedure to study kinetic pathways of
      multi-subunit, multi-state cooperative enzymes.

PMID- 15950240
TI  - Defining the structural basis for assembly of a transmembrane cytochrome.
AB  - To define the structural basis for cofactor binding to membrane proteins, we
      introduce a manageable model system, which allows us, for the first time, to
      study the influence of individual transmembrane helices and of single amino acid
      residues on the assembly of a transmembrane cytochrome. In vivo as well as in
      vitro analyses indicate central roles of single amino acid residues for either
      interaction of the transmembrane helices or for binding of the cofactor. The
      results clearly show that interaction of the PsbF transmembrane helix is
      independent from binding of the heme cofactor. On the other hand, binding of the
      cofactor highly depends on helix-helix interactions. By site-directed mutagenesis
      critical amino acid residues were identified, which are involved in the assembly
      of a functional transmembrane cytochrome. Especially, a highly conserved glycine
      residue is critical for interaction of the transmembrane helices and assembly of
      the cytochrome. Based on the two-stage-model of alpha-helical membrane protein
      folding, the presented results clearly indicate a third stage of membrane protein
      folding, in which a cofactor binds to a pre-assembled transmembrane protein.

PMID- 15950242
TI  - Are there reliable neuropsychological deficits in obsessive-compulsive disorder?
AB  - The aim of this study was to confirm in a large clinical sample that subjects
      with obsessive-compulsive disorder (OCD) have deficits on certain tasks of
      executive functioning, non-verbal memory, and/or motor speed. Our ultimate goal
      was to evaluate whether these deficits contribute to functional impairment and
      could be the target of a novel treatment intervention. Therefore, in a sample of
      convenience, the clinical characteristics and neuropsychological performance of
      adults with OCD and matched healthy controls were evaluated; neuropsychological
      tasks of executive functioning, non-verbal memory, and motor speed that have
      shown strong effects in prior studies were used. Primary analyses compared
      subjects with current OCD only (current-OCD, n=30), subjects with current OCD
      plus a comorbid disorder (comorbid-OCD, n=15), subjects with a history of OCD
      (n=15), and matched healthy controls (n=35). Secondary analyses examined whether
      clinical characteristics (e.g., OCD severity or medication status) were
      associated with neuropsychological performance. We found no significant overall
      differences in neuropsychological performance among the four groups. In pairwise
      comparisons, current-OCD subjects differed significantly from healthy controls
      only on the Benton Visual Retention Test. OCD severity had little effect and
      medication status had no effect on neuropsychological performance. In sum,
      contrary to our expectations, we found few differences in neuropsychological
      performance between OCD subjects and healthy controls. Whether there are reliable
      neuropsychological deficits in OCD that can be easily identified in a clinical
      sample and that contribute to functional impairment remains unclear and requires
      further study.

PMID- 15950241
TI  - Pancreatic trypsin activates human promatrix metalloproteinase-2.
AB  - In contrast to the prevalent view in the literature hitherto, the present study
      shows that pancreatic trypsin can activate human promatrix metalloproteinase-2
      (proMMP-2). It is shown that trypsin's ability to activate proMMP-2 is dependent
      on various environmental factors such as the level of exogenously added Ca(2+)
      and Brij-35, temperature, as well as trypsin concentration. The activation
      occurred as a sequential processing of the proenzyme, initially generating an
      active 62kDa species. This was followed by successive truncation of the C
      terminal domain, giving rise to active species of 56kDa, 52kDa and 50kDa. Tissue
      inhibitor of matrix metalloproteinases-2 (TIMP-2) prevented the trypsin-mediated
      C-terminal truncation, without affecting the generation of the 62kDa species,
      while the presence of EDTA increased the rate of the trypsin-mediated activation
      of proMMP-2. MALDI-TOF MS analysis of the 50kDa form indicated that trypsin
      generated active forms with either Lys87 or Trp90 as the N-terminal residue and
      Arg538 as a C-terminal residue. The trypsin-activated MMP-2 was active in
      solution against both synthetic and physiologic substrates, and the steady-state
      kinetic coefficients k(cat), K(m) and k(cat)/K(m) were determined for the enzyme
      activated either by APMA, membrane-type 1 matrix metalloproteinase (MT1-MMP) or
      trypsin. The trypsin-activated MMP-2 exhibited slightly lower k(cat) and
      k(cat)/K(m) values as well as a slightly higher K(i) value against TIMP-1
      compared to the enzyme activated by APMA or MT1-MMP. Docking studies of TIMP-1
      revealed that the slightly weaker binding of the inhibitor to the trypsin
      activated MMP-2 could be attributed to its shorter N terminus (Lys87/Trp90 versus
      Tyr81), as Phe83 and Arg86 interacted directly with the inhibitor. Our results
      suggest that the trypsin-activated MMP-2 possesses the catalytic and regulatory
      potential to be of significance in vivo.

PMID- 15950243
TI  - Tc-99m HMPAO brain SPECT findings in mild and moderate Alzheimer's disease:
      correlation with event related potentials.
AB  - We investigated whether brain SPECT findings show any differences between
      patients with mild and moderate Alzheimer's disease (AD) and to compare results
      with event related potentials (ERPs). Twenty-two patients with mild to moderate
      AD diagnosed according to NINCDS-ADRDA criteria and 10 age-matched control
      subjects were included in this prospective study. All subjects underwent ERP
      recordings and Tc-99m HMPAO brain SPECT study. Cortical perfusion index (CPI) was
      calculated as the ratio of cortical activity to the cerebellum activity. CPI was
      found to be statistically lower in bilaterally posterolateral temporal cortex and
      precuneus in the moderate AD compared to the control group. There was no
      statistically significant difference between the mild AD and control groups for
      CPI in any cortical areas. The mean P300 latency was statistically prolonged in
      the mild and moderate AD compared to the control group. In addition, in moderate
      AD P300 latency was longer than in mild AD. While the mean P300 amplitude was
      statistically reduced in moderate AD compared to the control and mild AD, there
      was no statistically significant difference between the mild AD and control
      groups. There was a strong negative correlation between P300 latency and CPI in
      the right and left precuneus in the moderate AD group. The present study
      suggested that Tc-99m HMPAO SPECT study is the more appropriate technique for
      patients with moderate AD rather than mild AD. Our results indicated that
      alterations in ERPs, especially prolongation of P300 latency could be a finding
      that occurred earlier than the deterioration in cerebral blood flow. We thought
      that precuneus is closely related to cognitive function and may have an important
      role in the pathophysiology of AD.

PMID- 15950244
TI  - The anti-apoptotic effects of nordihydroguaiaretic acid: inhibition of cPLA(2)
      activation during TNF-induced apoptosis arises from inhibition of calcium
      signaling.
AB  - Nordihydroguaiaretic acid (NDGA) is a plant lignan produced by Larrea tridentata,
      the creosote bush of the American southwest. In this report we examine the
      mechanism underlying the ability of NDGA to inhibit TNF-induced apoptosis. Our
      results show that NDGA blocks many key indicators of apoptosis. Caspase cleavage,
      mitochondrial inactivation, externalization of phosphatidyl serine, and (51)Cr
      release were all blocked by low micromolar concentrations of NDGA. NDGA also
      inhibited the cPLA(2)-dependent release of (3)H-arachidonic acid. We investigated
      this activity and found that NDGA prevented the rise in intracellular calcium
      necessary for the apoptotic activation of cPLA(2). On the other hand, NDGA did
      not interfere with the TNF-induced phosphorylation of cPLA(2), indicating that
      NDGA does not block all TNF-dependent signaling. Finally, we asked whether the
      anti-apoptotic effect of NDGA could be attributed to its anti-oxidant activity.
      Comparison with the effects of butylated hydroxyanisole (BHA) did not completely
      support this hypothesis. While BHA strongly inhibited caspase activation and
      partially blocked the release of (51)Cr, it was unable to significantly block the
      calcium response or the release of (3)H-arachidonic acid associated with TNF
      induced apoptosis. The anti-oxidant activity of NDGA may, therefore, explain some
      but not all of its anti-apoptotic activity.

PMID- 15950245
TI  - Comparative analysis of mutagenic potency of 1-nitro-acridine derivatives.
AB  - The anticancer effect of 1-nitro-9-hydroxyethylamino acridine (C-857), a compound
      belonging to the 1-nitroacridine class, has been well documented. Despite its
      therapeutic efficacy, the clinical development of C-857 has been impeded partly
      due to its high systemic toxicity. In an effort to enhance antitumor efficacy and
      lower toxicity, derivatives of C-857 have been synthesized with substitutions
      made at position C-4 and/or an esterified hydroxyl group in side chain at the C-9
      position. The introduction of a methyl group at C-4 resulted in C-1748, which has
      a significantly higher therapeutic efficacy and is being clinically developed as
      an anticancer agent for solid tumors. The present study was undertaken to
      correlate the mutagenicity of C-857, C-1748, C-1790, C-1872 and C-1873 with their
      cytotoxicity and their anti-tumor efficacy. The mutagenicity of these drugs was
      determined using three Ames Salmonella typhimurium strains TA1537, TA98 and
      TA102. The bacteria were treated with different molar concentrations, ranging
      from 10(-3) to 10(-12) M, of the drugs and drug-induced histidine revertants were
      then counted after a 48 h incubation. C-1748 did not induce any revertants in
      both TA1537 and TA98 at a dose of 10(-6) M, whereas, C-857 at the same dose
      induced approximately 842 and approximately 1034 revertants respectively. In
      TA102, mutagenicity was lower than observed with TA98 and TA1537 with highest
      revertants observed at 10(-5) M with C-857 (approximately 606) and C-1748
      (approximately 108). Higher mutagenicity was observed in the derivatives C-1790,
      C-1872 and C-1873 compared to C-1748, but lower than C-857. These studies
      demonstrate that C-1748 has the least mutagenic potential, with a much higher
      antitumor effect in prostate cancer and is a promising chemotherapeutic agent for
      clinical development.

PMID- 15950246
TI  - Polybrominated diphenyl ethers (PBDEs) in sediments and mussel tissues from Hong
      Kong marine waters.
AB  - Sediments and green-lipped mussels, Perna viridis, were used to investigate
      concentrations of polybrominated diphenyl ethers (PBDEs) in Hong Kong's marine
      environment. PBDEs have been used extensively over the past two decades as flame
      retardants in polymer additives for a variety of plastics, computers, furniture,
      building materials, and fabrics. Many measurements of PBDEs in various
      environmental matrices have been reported from Belgium, Holland, Japan, Europe
      and North America, but few measurements are available for the southeast Asian
      region and Hong Kong. PBDE congeners (n=15) were measured in 13 sediments and
      nine mussel samples, taken from Hong Kong marine waters. The Sigma15PBDEs in
      sediments ranged between 1.7 and 53.6 ng g(-1) dry wt, with the highest
      concentrations located around the most heavily populated areas of Victoria
      Harbour and Sai Kung, while the lowest concentrations of Sigma15PBDEs were found
      at more remote locations of Sha Tau Kok, Wong Chuk Bay, Castle Peak Bay, and Gold
      Coast. Sigma15PBDEs ranged from 27.0 to 83.7 ng g(-1) dry wt of mussel tissues.
      Although not identical, most of the congeners in sediments were found in mussel
      tissues, with BDE-47, BDE-99, BDE-153 and BDE-183 being the most prominent in
      both matrices. On the basis of a literature survey, the concentrations of PBDEs
      reported in Hong Kong sediments and mussel tissues are amongst the highest in the
      world.

PMID- 15950247
TI  - Neuroprotectant effects of iso-osmolar D-mannitol to prevent Pacific ciguatoxin-1
      induced alterations in neuronal excitability: a comparison with other osmotic
      agents and free radical scavengers.
AB  - The basis for the neuroprotectant effect of D-mannitol in reducing the sensory
      neurological disturbances seen in ciguatera poisoning, is unclear. Pacific
      ciguatoxin-1 (P-CTX-1), at a concentration 10 nM, caused a statistically
      significant swelling of rat sensory dorsal root ganglia (DRG) neurons that was
      reversed by hyperosmolar 50 mM D-mannitol. However, using electron paramagnetic
      resonance (EPR) spectroscopy, it was found that P-CTX-1 failed to generate
      hydroxyl free radicals at concentrations of toxin that caused profound effects on
      neuronal excitability. Whole-cell patch-clamp recordings from DRG neurons
      revealed that both hyper- and iso-osmolar 50 mM D-mannitol prevented the membrane
      depolarisation and repetitive firing of action potentials induced by P-CTX-1. In
      addition, both hyper- and iso-osmolar 50 mM D-mannitol prevented the
      hyperpolarising shift in steady-state inactivation and the rise in leakage
      current through tetrodotoxin (TTX)-sensitive Na(v) channels, as well as the
      increased rate of recovery from inactivation of TTX-resistant Na(v) channels
      induced by P-CTX-1. D-Mannitol also reduced, but did not prevent, the inhibition
      of peak TTX-sensitive and TTX-resistant I(Na) amplitude by P-CTX-1. Additional
      experiments using hyper- and iso-osmolar D-sorbitol, hyperosmolar sucrose and the
      free radical scavenging agents Trolox and L-ascorbic acid showed that these
      agents, unlike D-mannitol, failed to prevent the effects of P-CTX-1 on spike
      electrogenesis and Na(v) channel gating. These selective actions of D-mannitol
      indicate that it does not act purely as an osmotic agent to reduce swelling of
      nerves, but involves a more complex action dependent on the Na(v) channel
      subtype, possibly to alter or reduce toxin association.

PMID- 15950248
TI  - Endocannabinoids restrict hippocampal long-term potentiation via CB1.
AB  - Cannabinoid ligands alter cognition and prevent long-term potentiation (LTP) of
      synaptic transmission, but the influence of endogenously formed cannabinoids
      (eCBs) on hippocampal LTP remains ambiguous. In the accompanying study, we showed
      that eCB levels regulated by cyclooxygenase-2 (COX-2) tonically decrease basal
      excitatory transmission. Here, we investigated the influence of eCBs on LTP in
      CA1 hippocampus. LTP elicited by moderate stimulations (20 or 50 pulses) was
      facilitated in slices treated with a CB1 antagonist, whereas LTP elicited with
      robust stimulations (100 or 200 pulses) was unchanged by CB1 blockade. LTP
      elicited with theta-burst stimulations also was facilitated with CB1 blockade,
      revealing a tonic inhibitory influence of eCBs on LTP induction. Conversely,
      inhibition of COX-2 prevented LTP elicited with theta burst stimulations.
      Inhibition of COX-1 or other routes of eCB degradation did not affect LTP. We
      conclude that COX-2 regulates the formation of CB1 ligands that negatively
      regulate LTP.

PMID- 15950249
TI  - Circadian rhythm of locomotor activity in the four-striped field mouse, Rhabdomys
      pumilio: a diurnal African rodent.
AB  - Although humans are diurnal in behaviour, animal models used for the study of
      circadian rhythms are mainly restricted to nocturnal rodents. This study focussed
      on the circadian behaviour of a rodent from South Africa that has a preference
      for daylight, the four-striped field mouse, Rhabdomys pumilio. In order to
      characterise the behavioural pattern of daily activity, locomotor rhythms were
      studied under different light regimes using an automated data recording system.
      Under conditions of natural daylight, which include dawn and dusk transitions, R.
      pumilio exhibited activity restricted to the daytime period. Activity was
      concentrated around morning and evening with a decrease during mid-day. A similar
      diurnal preference pattern of behaviour was recorded under a light-dark cycle of
      artificial illumination. Under conditions of constant darkness, the four-striped
      field mouse exhibited a free-running circadian rhythm of locomotor activity with
      activity concentrated during the subjective day. Free-running rhythms varied
      greatly between individuals, from slightly less to slightly more than 24 h (range
      = 23.10 to 24.80 h). Under conditions of constant light, the mice were more
      active during subjective day, but the free-running rhythm in all individuals was
      consistently longer than 24 h (range = 24.30 to 24.79 h).

PMID- 15950250
TI  - Diterpenoid quinones from rosemary (Rosmarinus officinalis L.).
AB  - Two new abietane-type diterpenoid o-quinones, 7beta-methoxyabieta-8,13-diene
      11,12-dione-(20,6beta)-olide (rosmaquinone A) (1) and 7alpha-methoxyabieta-8,13
      diene-11,12-dione-(20,6beta)-olide (rosmaquinone B) (2), together with six known
      compounds were isolated from the aerial parts of Rosmarinus officinalis L. The
      structures of the new compounds were determined by extensive spectroscopic
      analysis, including IR, UV, HR-EIMS, 1D and 2D 400 MHz NMR data (1H, 13C NMR,
      DEPT, 1H-1H COSY, HMQC, HMBC and NOEs).

PMID- 15950251
TI  - Evolution of beta-lactam biosynthesis genes and recruitment of trans-acting
      factors.
AB  - Penicillins and cephalosporins belong chemically to the group of beta-lactam
      antibiotics. The formation of hydrophobic penicillins has been reported in fungi
      only, notably Penicillium chrysogenum and Emericella nidulans, whereas the
      hydrophilic cephalosporins are produced by both fungi, e.g., Acremonium
      chrysogenum (cephalosporin C), and bacteria. The producing bacteria include Gram
      negatives and Gram-positives, e.g. Lysobacter lactamdurans (cephabacins) and
      Streptomyces clavuligerus (cephamycin C), respectively. For a long time the
      evolutionary origin of beta-lactam biosynthesis genes in fungi has been
      discussed. As often, there are arguments for both hypotheses, i.e., horizontal
      gene transfer from bacteria to fungi versus vertical descent. There were strong
      arguments in favour of horizontal gene transfer, e.g., fungal genes were
      clustered or some genes lack introns. The recent identification and
      characterisation of cis-/trans-elements involved in the regulation of the beta
      lactam biosynthesis genes has provided new arguments in favour of horizontal gene
      transfer. In contrast to the bacterium S. clavuligerus, all regulators of fungal
      beta-lactam biosynthesis genes represent wide-domain regulators which were
      recruited to also regulate the beta-lactam biosynthesis genes. Moreover, the
      fungal regulatory genes are not part of the gene cluster. If bacterial regulators
      were co-transferred with the gene cluster from bacteria to fungi, most likely
      they would have been non-functional in eukaryotes and lost during evolution.
      Alternatively, it is conceivable that only a part of the beta-lactam biosynthesis
      gene cluster was transferred to some fungi, e.g., the acvA and ipnA gene without
      a regulatory gene.

PMID- 15950252
TI  - Collaborative research partnerships with disadvantaged communities: challenges
      and potential solutions.
AB  - Community/campus research collaborations face multiple challenges. An
      understanding of the community's background, history, habits and traditions,
      values and mode of operations is required. This article narrates a 3-year
      experience of undertaking collaborative public health research with five
      disadvantaged communities in various provinces of South Africa. Based on the
      experience, five main challenges exist: the value systems of those collaborating
      in the research; the stakeholders' costs and benefits of being involved; issues
      of empowerment and capacity transfer; the need for multidisciplinary research
      approaches; and the prerequisite of the clarity of relationships and roles
      between researcher and community. Categorized under the five main challenges are
      examples of 19 interlacing 'concepts' that detailed the South African research
      partnership from the perspective of the processes, dealings and daily
      difficulties. Examples of the challenges and concepts are highlighted from the
      author's research experiences with disadvantaged communities. These challenges
      increase exponentially with the inclusion of more research sites, more
      stakeholders or when undertaking cluster research. Possible preventative measures
      or solutions to the problems are suggested. Both the 'town' and 'gown' partners
      are required to attend to a multitude of factors when embarking on collaborative
      community-based research.

PMID- 15950253
TI  - An alternative conformation of the gp41 heptad repeat 1 region coiled coil exists
      in the human immunodeficiency virus (HIV-1) envelope glycoprotein precursor.
AB  - The human immunodeficiency virus (HIV-1) transmembrane envelope glycoprotein,
      gp41, which mediates virus-cell fusion, exists in at least three different
      conformations within the trimeric envelope glycoprotein complex. The structures
      of the prefusogenic and intermediate states are unknown; structures representing
      the postfusion state have been solved. In the postfusion conformation, three
      helical heptad repeat 2 (HR2) regions pack in an antiparallel fashion into the
      hydrophobic grooves on the surface of a triple-helical coiled coil formed by the
      heptad repeat 1 (HR1) regions. We studied the prefusogenic conformation of gp41
      by mutagenic alteration of membrane-anchored and soluble forms of the HIV-1
      envelope glycoproteins. Our results indicate that, in the HIV-1 envelope
      glycoprotein precursor, the gp41 HR1 region is in a conformation distinct from
      that of a trimeric coiled coil. Thus, the central gp41 coiled coil is formed
      during the transition of the HIV-1 envelope glycoproteins from the precursor
      state to the receptor-bound intermediate.

PMID- 15950254
TI  - Infection of lung epithelial cells and induction of pulmonary adenocarcinoma is
      not the most common outcome of naturally occurring JSRV infection during the
      commercial lifespan of sheep.
AB  - Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary
      adenocarcinoma (OPA). In this study, we followed over a 31-month period the
      natural transmission of JSRV in adult sheep and in their offspring. We
      established groups derived from flocks with either a high or low incidence of OPA
      and monitored virus transmission, clinical disease and macroscopic/microscopic
      lung lesions at necropsy. Results obtained show that (i) JSRV infection can occur
      perinatally or in the first few months of life in lambs and in adult sheep; (ii)
      only a minority of JSRV-infected animals develop clinical disease during their
      commercial lifespan; and (iii) JSRV is more readily detectable in peripheral
      blood leucocytes and lymphoid organs than in the lungs. These data support a
      model of opportunistic JSRV infection and tumorigenic conversion of type II
      pneumocytes/Clara cells in the lungs, while lymphoreticular cells serve as the
      principal virus reservoir.

PMID- 15950255
TI  - Criteria interactions across visual attributes.
AB  - Judgmental interference in dual tasks has been demonstrated in conditions where
      the detection or discrimination of different contrast increments applied to two
      stimuli presented simultaneously or in sequence. The present work demonstrates
      such interference for changes along two distinct visual features, namely contrast
      and orientation, when simultaneously applied to the same or to two distinct
      objects (Gabor-patches). The interference reveals itself in the use of quasi
      equal decision criteria for both dimensions, in conflict with an optimal behavior
      requiring that criteria be proportional to the sensitivities for the distinct
      changes. The quasi-equality of the criteria assessed for contrast and orientation
      changes implies the equality of the internal noises characterizing the respective
      detection process, hence suggesting that they are limited at the decision level.
      Among the conceptual consequences of this limitation are the existence of a meta
      attribute decisional dimension (tantamount to that of a "central executive
      system") and the questionable merits of probability summation over spatial
      channels. In addition, the data show a significant sensitivity drop in the dual-
      with respect to the single-task conditions, all the more so when the modulated
      features belong to two objects rather than to the same object. While the
      sensitivity drop in dual tasks is the standard trademark of distributed
      attention, it is argued that decisional interference is yet another aspect of it.

PMID- 15950256
TI  - Phytoremediation of effluents from aluminum smelters: a study of Al retention in
      mesocosms containing aquatic plants.
AB  - Four mesocosms were exposed to circumneutral and aluminum (Al)-rich wastewater
      during two successive summers (2000, 2001). The goals of the study were to
      measure the bioaccumulation of dissolved Al by the aquatic plants Typha
      latifolia, Lemna minor, Nuphar variegatum and Potamogeton epihydrus, and to
      evaluate their importance in the retention of Al by the mesocosms. In 2000, inlet
      concentrations of total monomeric Al were reduced by 56% and 29% at the Arvida
      and Laterriere mesocosms, respectively, whereas in 2001 inlet dissolved Al
      concentrations in the inlet decreased by 40% and 33%. L. minor had the highest Al
      uptake rate (0.8--17 mg Al g(-1)d(-1)). However, because T. latifolia (cattails)
      yielded the highest biomass, it was responsible for 99% of the Al uptake, largely
      in its root tissue. In 2001, Al uptake by macrophytes accounted for 2--4% and 15-
      54% of the total Al retained by the Laterriere and Arvida mesocosms,
      respectively. In the Laterriere mesocosms, Al uptake by cattails could account
      for 12% and 18% of the dissolved Al retained by both mesocosms. In contrast,
      dissolved Al was not significantly reduced in the Arvida enclosures, yet cattails
      did accumulate Al in their roots. Further research is needed to identify the
      species community composition that would optimize dissolved Al retention.

PMID- 15950257
TI  - Adsorption/desorption of linear alkylbenzenesulfonate (LAS) and azoproteins
      by/from activated sludge flocs.
AB  - Our study investigated the adsorption/desorption by/from activated sludge flocs,
      dispersed in river water or in diluted wastewater, of organic compounds (C(11)
      LAS, azoalbumin and azocasein) at concentrations relevant to environmental
      conditions. Activated sludge flocs, used as a model of biological aggregates, are
      characterized by a very heterogeneous matrix able to sorb the three organic
      compounds tested at 4 degrees C. The adsorbed amount of C(11)-LAS by activated
      sludge flocs was higher than that of azocasein or azoalbumin, as shown by the
      Freundlich parameters (K(ads)=8.6+/-1.7, 1.6+/-0.3 and 0.3+/-0.1 micromol(1
      1/n)g(-1)l(1/n) for C(11)-LAS, azocasein and azoalbumin, respectively; n=3
      sludges). C(11)-LAS sorption from activated sludge appeared to be partially
      reversible in river water, while a marked hysteresis phenomenon was observed for
      azocasein and azoalbumin, implying a low degree of reversibility in their
      exchange between activated sludge and river water. It has also been displayed
      that the conductivity variation of bulk water (comprised between 214 and 838
      microS cm(-1)) exerted no dramatic effect on the C(11)-LAS desorption from
      activated sludge flocs, while a little effect of it on azocasein desorption was
      observed. Thus, biological aggregates as activated sludge flocs can serve as an
      intermediate carrier for C(11)-LAS, while it represents a sink for proteins.

PMID- 15950258
TI  - Kinetic assessment of the potassium ferrate(VI) oxidation of antibacterial drug
      sulfamethoxazole.
AB  - Sulfamethoxazole (SMX), a worldwide-applied antibacterial drug, was recently
      found in surface waters and in secondary wastewater effluents, which may result
      in ecotoxical effects in the environment. Herein, removal of SMX by
      environmentally-friendly oxidant, potassium ferrate(VI) (K(2)FeO(4)), is sought
      by studying the kinetics of the reaction between Fe(VI) and SMX as a function of
      pH (6.93-9.50) and temperature (15-45 degrees C). The rate law for the oxidation
      of SMX by Fe(VI) is first-order with respect to each reactant. The observed
      second-order rate constant decreased non-linearly from 1.33+/-0.08 x 10(3) M(
      1)s(-1) to 1.33+/-0.10 x 10(0) M(-1)s(-1) with an increase of pH from 7.00 to
      9.50. This is related to protonation of Fe(VI) (HFeO(4)(-) <==> H(+) + FeO(4)(2
      ); pK(a,HFeO(4)) = 7.23) and sulfamethoxazole (SH <==> H(+) + S(-);
      pK(a,SH)=5.7). The estimated rate constants were k(11)(HFeO(4)(-) + SH) = 3.0 x
      10(4) M(-1)s(-1), k(12)(HFeO(4)(-) + S(-)) = 1.7 x 10(2) M(-1)s(-1), and k(13)
      (FeO(4)(2-) + SH) = 1.2 x 10(0) M(-1)s(-1). The energy of activation at pH 7.0
      was found to be 1.86+/-0.04 kJ mol(-1). If excess potassium ferrate(VI)
      concentration (10 microM) is used than the SMX in water, the half-life of the
      reaction using a rate constant obtained in our study would be approximately 2 min
      at pH 7. The reaction rates are pH dependent; thus, so are the half-lives of the
      reactions. The results suggest that K(2)FeO(4) has the potential to serve as an
      oxidative treatment chemical for removing SMX in water.

PMID- 15950259
TI  - The partitioning of alkylphenolic surfactants and polybrominated diphenyl ether
      flame retardants in activated sludge batch tests.
AB  - Polybrominated diphenyl ethers and nonylphenol polyethoxylates have been reported
      to be estrogenic and may enter the aquatic environment through the discharge of
      treated sewage effluent. Therefore, their fate during wastewater treatment
      processes is an important factor in determining their environmental impact. Batch
      tests with activated sludge from a Husmann apparatus were used to determine the
      effects of physico-chemical properties and sludge characteristics on the
      partitioning of polybrominated diphenyl ether flame retardants and nonylphenol
      polyethoxylate surfactants during biological wastewater treatment. Hydrophobic
      compounds, those with high logK(ow) values, were sorbed more rapidly and to a
      greater extent to the solid phase than more soluble compounds. For these
      hydrophobic compounds sorption may become an increasingly important removal
      mechanism as sludge age and therefore solids content increase. The initial rate
      of partitioning was greatest for the most hydrophobic compounds but all rates
      diminished with time as a result of progressive saturation of sorbent binding
      sites, a reduction of sorbate availability and as a consequence of the system
      reaching equilibrium. The sorption of polybrominated diphenyl ethers fit
      Freundlich adsorption isotherms demonstrating generally increasing adsorption
      capacity and efficiency with increasing hydrophobic nature. A correlation between
      increasing logK(ow) and increasing organic matter content was also observed for
      both polybrominated diphenyl ethers and nonylphenol polyethoxylates indicating
      the organic content of mixed liquor will also be influential in removing
      compounds during wastewater treatment.

PMID- 15950260
TI  - QSARs for the aquatic toxicity of aromatic aldehydes from Tetrahymena data.
AB  - The aim of the study was to develop quantitative structure-activity relationships
      (QSARs) for a large group of 77 aromatic aldehydes tested for acute toxicity to
      the ciliate Tetrahymena pyriformis using mechanistically interpretable
      descriptors. The resulting QSARs revealed that the 1-octanol/water partition
      coefficient (log K(ow)), is the most important descriptor of aldehyde aquatic
      toxic potency. The model with log K(ow) was improved by adding electronic
      descriptor (the maximum acceptor superdelocalizability in a molecule--A(max))
      based on calculations with the semi-empirical AM1 model. The two descriptors
      reflect the two main processes responsible for demonstration of acute aquatic
      toxicity, namely penetration through cell membranes (log K(ow)) and interaction
      with the biomacromolecules (A(max)) into the cells. Results showed that generally
      the studied group of aldehydes could be modeled by this simple two-descriptor
      approach. However, the group of 2- and/or 4-hydroxylated aldehydes demonstrates
      enhanced toxicity compared to the other aldehydes. Transformation to quinone-like
      structures is proposed as the explanation for this enhanced potency. The 2-
      and/or 4-hydroxylated aldehydes are modeled successfully by [log(1/IGC50) =
      0.540(0.038) log K(ow) + 8.30(2.88)A(max) - 3.11(0.92), n = 25, R2 = 0.916,
      R(CV)2 = 0.896, s = 0.141, F = 120], while the other aldehydes are modeled by the
      relationship [log(1/IGC50) = 0.583 (0.034)log K(ow) + 9.80(2.62)A(max) - 4.04
      (0.85), n = 52, R2 = 0.864, R(CV)2 = 0.844, s = 0.203, F = 156], which is similar
      to the general benzene model.

PMID- 15950262
TI  - Characterization of pore scale NAPL morphology in homogeneous sands as a function
      of grain size and NAPL dissolution.
AB  - In this study, we investigate pore scale morphology of nonaqueous phase liquids
      (NAPLs) trapped in different pore sizes using tracer techniques. Specific
      interfacial area and saturation of NAPL trapped in homogeneous sands were
      measured using the interfacial and partitioning tracer techniques. The observed
      NAPL-water interfacial areas increased in a log-linear fashion with decreasing
      sand grain size, but showed no clear trend with residual NAPL saturation formed
      in the various grain sizes. The measured values were used to calculate the NAPL
      morphology index, which characterizes the spatial NAPL distribution within the
      pore space. The NAPL morphology indices, increased exponentially with decreasing
      grain size, indicating that the NAPL becomes smaller, but more blobs. For a fixed
      grain size, the specific interfacial area and saturation of the NAPL were
      measured following changes caused by dissolution using alcohol. The observed
      interfacial areas showed a decrease linearly as a function of the NAPL
      saturation.

PMID- 15950263
TI  - Environmental assessment of different advanced oxidation processes applied to a
      bleaching Kraft mill effluent.
AB  - Different advanced oxidation processes (AOPs) have been applied to remove the
      organic carbon content of a paper mill effluent originating from the Kraft pulp
      bleaching process. The considered AOPs were: TiO(2)-mediated heterogeneous
      photocatalysis, TiO(2)-mediated heterogeneous photocatalysis assisted with
      H(2)O(2), TiO(2)-mediated heterogeneous photocatalysis coupled with Fenton, photo
      Fenton, ozonation and ozonation with UV-A light irradiation. The application of
      the selected AOPs all resulted in a considerable decrease in dissolved organic
      carbon (DOC) content with variable treatment efficiencies depending upon the
      nature/type of the applied AOP. A Life Cycle Assessment (LCA) study was used as a
      tool to compare the different AOPs in terms of their environmental impact.
      Heterogeneous photocatalysis coupled with the Fenton's reagent proved to have the
      lowest environmental impact accompanied with a moderate-to-high DOC removal rate.
      On the other hand, heterogeneous photocatalysis appeared to be the worst AOP both
      in terms of DOC abatement rate and environmental impact. For the studied AOPs,
      LCA has indicated that the environmental impact was attributable to the high
      electrical energy (power) consumption necessary to run a UV-A lamp or to produce
      ozone.

PMID- 15950264
TI  - Some parting words for Jan Jelinek (February 6, 1926-October 3, 2004).

PMID- 15950265
TI  - Dinoflagellate cysts and hydrographical change in Gullmar Fjord, west coast of
      Sweden.
AB  - This high-resolution study of the latest Holocene dinoflagellate cyst record from
      Gullmar Fjord, on the west coast of Sweden, provides evidence for the recognition
      of two major dinoflagellate communities within the fjord over the last 85 years.
      These communities may have their origins with the history of cultural
      eutrophication within the region, but are more likely to be associated with the
      wider phenomenon of the North Atlantic Oscillation and/or the complex
      hydrographical response of the fjord to various changing climatic environments
      between 1915 and 1999. The changing dinoflagellate cyst populations are compared
      in detail with the many hydrographical parameters available from this well
      studied fjord with its long instrumental records. Indeed the dinoflagellate cysts
      fail to demonstrate a convincing ongoing eutrophication record for the fjord but
      do show a major change in the cyst assemblages at about 1969/1970 at a time when
      the NAO was changing from a negative phase to the present-day positive phase.
      Gullmar Fjord is important in the history of dinoflagellate cyst studies, being
      the site of the 1954 study by Erdtman in which viable cysts, produced within the
      phytoplankton, were first documented within the water column.

PMID- 15950266
TI  - The Almaden district (Spain): anatomy of one of the world's largest Hg
      contaminated sites.
AB  - We present data from an early reconnaissance survey (stream sediments, soil, and
      water Hg chemistry; plants and water crustaceans Hg intake) of the Almaden
      district (central Spain), that was carried out to establish the potential
      environmental hazards derived from the anomalous mercury concentrations measured
      in this realm. The Almaden mercury district (approximately 300 km2) can be
      regarded as the largest geochemical anomaly of mercury on Earth. The district
      includes a series of mercury mineral deposits, having in common a simple
      mineralogy (dominant cinnabar: HgS, and minor pyrite: FeS2). The ore deposits
      have been mined for more than 2000 years, and the main mine of the district
      (Almaden), has been active from Roman times to present day with almost no
      interruptions. The mercury distribution in soils of the district reveals the
      existence of high, and extremely high mercury values (up to 8889 microg g(-1)),
      whereas concentrations in stream sediments and waters reach exceptional values of
      up to 16,000 microg g(-1) and 11,200 ng l(-1) respectively. On the other hand,
      very high concentrations of methylmercury (MeHg) have been detected in calcines
      (up to 3100 ng g(-1)), sediments (0.32-82 ng g(-1)), and waters (0.040-30 ng l(
      1)). Mercury gets incorporated to edible river crustaceans and plants. The red
      swamp crayfish Procambarus clarkii, has Hg concentrations of up to 9060 ng g(-1)
      (muscle) and 26,150 ng g(-1) (hepatopancreas). Regarding plants, the local wild
      asparagus (Asparagus acutifolius) yields values of up to 298 microg g(-1) Hg.
      Mercury also escapes to the atmosphere, and mineral deposits, together with
      metallurgical activities, generate strong anomalies of atmospheric Hg. The most
      important concentrations relate to the emissions from the Almaden metallurgical
      roaster, in the order of 14,000 ng Hg m(-3). Additionally, large open pit
      operations also contribute to the district atmospheric pool of mercury, with high
      concentrations above 1000 ng Hg m(-3). Thus, no system (rocks, soils, sediments,
      waters, atmosphere, biota) in the Almaden district is free from strong Hg
      contamination.

PMID- 15950268
TI  - Diagnosing pulmonary embolism: experience with spiral CT pulmonary angiography in
      gynecologic oncology.
AB  - OBJECTIVES: To review our experience with the diagnosis and prognosis of
      pulmonary embolism (PE) in gynecologic oncology patients. METHODS: Spiral CT
      pulmonary angiography (CTPA) studies on gynecologic oncology patients were
      collected from our radiology database from 6/2001 to 6/2003. Patient charts were
      retrospectively reviewed. Data were abstracted relative to presenting symptoms,
      demographics and laboratory and diagnostic evaluations. Patient data were
      compared using chi-square contingency tables and logistic regression analysis.
      Survival was studied using the Kaplan-Meier method and the log rank test. The
      effect of PE on survival was adjusted using a proportional hazards regression
      model. RESULTS: One-hundred and eleven CTPA studies were performed over 2 years
      and 25 patients were diagnosed with PE. Both PE (n = 25) and non-PE (n = 86)
      groups were similar for age, race, BMI and cancer diagnosis. Tachycardia (P =
      0.02, OR = 3.03 [95% CI 1.16-7.94]) and leukocytosis (P = 0.04, OR = 2.93[95% CI
      1.05-8.18]) were more frequent among PE patients and confirmed as independently
      prognostic of PE. All other clinical and laboratory findings were similar between
      patients with and without PE. Overall survival for patients with and without PE
      was 63% versus 94%, respectively, at 2 years (P = 0.02). CONCLUSION: In a
      gynecologic oncology patient with high clinical suspicion for PE, our clinical
      pre-test probability was 23.0%. Two-year mortality rates were 6-fold higher for
      patients diagnosed with PE. The significant overlap in clinical presentations,
      multiple risk factors and higher mortality rates encourage the aggressive
      diagnosis and treatment of PE among this population. Further work is needed to
      reduce the incidence and mortality rate of PE.

PMID- 15950269
TI  - Epipregnanolone and a novel synthetic neuroactive steroid reduce alcohol self
      administration in rats.
AB  - This study was designed to compare the effects of several neuroactive steroids
      with varying patterns of modulation of gamma-aminobutyric acid (GABA)(A) and NMDA
      receptors on operant self-administration of ethanol or water. Once stable
      responding for 10% (w/v) ethanol was achieved, separate test sessions were
      conducted in which male Wistar rats were allowed to self-administer ethanol or
      water following pre-treatment with vehicle or one of the following neuroactive
      steroids: (3beta,5beta)-3-hydroxypregnan-20-one (epipregnanolone; 5, 10, 20
      mg/kg; n=12), (3alpha,5beta)-20-oxo-pregnane-3-carboxylic acid (PCA; 10, 20, 30
      mg/kg n=10), (3alpha,5beta)-3-hydroxypregnan-20-one hemisuccinate (pregnanolone
      hemisuccinate; 5, 10, 20 mg/kg; n=12) and (3alpha,5alpha)-3-hydroxyandrostan-17
      one hemisuccinate (androsterone hemisuccinate; 5, 10, 20 mg/kg; n=11). The effect
      of the 3beta-epimer of PCA, (3beta,5beta)-20-oxo-pregnane-3-carboxylic acid (10,
      20, 30 mg/kg; n=9), on ethanol self-administration was also examined. The
      compounds were administered using a Latin-square design 45 min prior to the
      weekly test sessions. The effects of the 30 mg/kg dose of the steroidal
      hemisuccinates on ethanol intake were also examined 5 min after administration of
      these drugs. Both epipregnanolone and PCA attenuated ethanol self-administration.
      However, neither of the hemisuccinate compounds significantly altered this
      behavior. The steroidal hemisuccinates (30 mg/kg; n=7) were also tested 5 min
      before behavior testing and had no effect on ethanol intake 5 min after
      administration. The 3beta-epimer of PCA also failed to alter ethanol intake. None
      of the test compounds altered water intake. In electrophysiological studies, the
      effects of PCA and androsterone hemisuccinate on evoked GABA(A) receptor-mediated
      inhibitory postsynaptic currents (GABA(A)-IPSCs) was examined in brain slices of
      the amygdala. PCA had a stimulatory effect at concentrations of 5 and 25 muM.
      Androsterone hemisuccinate had no agonist activity. The ability of
      epipregnanolone and PCA to alter ethanol intake appears to be related to
      different inhibitory actions of these compounds on either GABA(A) or NMDA
      receptors, respectively. Thus, dual modulation of these systems by selected
      neuroactive steroids may offer potential for modifying the reinforcing effects of
      alcohol.

PMID- 15950270
TI  - Recombinase-mediated mouse transgenesis by intracytoplasmic sperm injection.
AB  - The low efficiency of current microinjection-based animal transgenesis techniques
      is largely the result of poor embryo survival. We have developed a new, bacterial
      recombinase-based transgenesis method. Intracytoplasmic sperm injection (ICSI) of
      single stranded DNA (ssDNA) complexed with E. coli recombinase RecA into mouse
      metaphaseII (MII) arrested oocytes resulted in RecA-dependent transgenesis. This
      approach offers significant advantages over pronuclear microinjection and
      previous ICSI-based transgenesis approaches in terms of improved embryo survival,
      which translates into greater transgenesis efficiency. It also opens the
      possibility to attempt experiments, which may affect gene targeting by homologous
      recombination into DNA of mammalian single celled pre-implantation embryos.

PMID- 15950271
TI  - Theoretical aspects of canine cryopreserved semen evaluation.
AB  - Evaluation of canine cryopreserved semen has the ultimate goal of determining if
      an individual frozen ejaculate will have acceptable fertility. This is difficult
      in that there is no accepted normal fertility for the dog. The fertility of the
      female also plays a crucial role in estimating the fertility of the male. Poor
      female fertility can make a fertile male appear less fertile. Variability of
      animals, breeding technique, breeding timing, and number of cells inseminated
      make comparisons in canine fertility difficult to truly measure. Many more
      animals are needed to provide meaningful statistical results than are usually
      used. Several tests, including motility in bright field and phase contrast
      microscopy, computer analysis of motility, sperm morphology, sperm membrane
      integrity, capacitation and sperm function tests have been investigated to
      predict fertility, however few of these tests have actually been correlated with
      fertility. More work is needed to create one or more tests that accurately
      predict fertility of cryopreserved canine semen.

PMID- 15950272
TI  - Factors affecting the success of oocyte transfer in a clinical program for
      subfertile mares.
AB  - Oocyte transfer is a potential method to produce offspring from valuable mares
      that cannot carry a pregnancy or produce embryos. From 2000 through 2004, 86
      mares, 19.2 +/- 0.4 yr of age (mean +/- S.E.M.), were used as oocyte donors in a
      clinical program at Colorado State University. Oocytes were collected from 77%
      (548/710) of preovulatory follicles and during 96% (548/570) of cycles. Oocytes
      were collected 21.0+/-0.1h after administration of hCG to estrous donors and
      cultured 16.4 +/- 0.2 h prior to transfer into recipients' oviducts. At 16 and 50
      d after transfer, pregnancies were detected in 201 of 504 (40%) and 159 of 504
      (32%) of recipients, respectively, with an embryo-loss rate of 21% (42/201).
      Pregnancy rates were similar (P > 0.05) for cyclic and noncyclic recipients and
      for recipients inseminated with cooled, fresh or frozen semen. One or more
      recipients were detected pregnant at 16 and 50 d, respectively, for 80% (69/86)
      and 71% (61/86) of donors. More donors <20 than > or = 20 yr (mean ages +/-
      S.E.M. of 15.5 +/- 0.4 and 23.0 +/- 0.3 yr, respectively) tended (P = 0.1) to
      have one or more pregnant recipients at 50 d (36/45, 80%; 28/45, 62%,
      respectively). Results of the program confirm that pregnancies can consistently
      be obtained from older, subfertile mares using oocyte transfer.

PMID- 15950273
TI  - Endocrine control of estrous cycle in mithun (Bos frontalis).
AB  - The objective of the present study was to establish the profiles of luteinising
      hormone (LH), follicle stimulating hormone (FSH), estradiol 17beta (E2) and
      progesterone (P4) secretion and their interrelationships during the natural
      estrous cycle of mithun (Bos frontalis). Daily blood samples were collected from
      second or third postpartum estrous cycles for determination of plasma
      concentrations of LH, FSH, E2 and P4. Concentration of P4 was found to be lowest
      on the day of estrus. It increased following estrus, attained the highest
      concentration on day 11 and decreased thereafter. Concentrations of LH and FSH
      varied significantly (p<0.01) during the first and last 6 days of the cycle and
      their variations were found to be synchronised. Both LH and FSH attained a
      biphasic peak during the estrous cycle. This biphasic peak lasted on from day -5
      to day 3 of the cycle. The variations in maximum LH and FSH concentrations of
      both the phases did not differ significantly. During the entire estrous cycle,
      the E2 concentrations attained either one peak or two peaks. The first peak,
      approximately on day 4 before estrus was common in all animals. One additional
      peak was found on the day of estrus in 45% animals. A significant (p<0.01)
      negative relationship was found between P4 and, LH and FSH during the first and
      last 6 days of cycle. But a significant (p<or=0.01) negative relationship between
      E2 and, LH and FSH was found only during the last 6 days of cycle. The results
      suggest a negative feedback mechanism on LH and FSH release by E2 and P4 during
      the respective phases of cycle. A sustained increase in LH and FSH levels during
      the period before estrus was probably necessary for the final maturation of
      ovulatory follicle and subsequent ovulation.

PMID- 15950274
TI  - Benthic biotope index for classifying habitats in the Sado Estuary: Portugal.
AB  - An integration of sediment physical, chemical, biological, and toxicity data is
      necessary for a meaningful interpretation of the complex sediment conditions in
      the marine environment. Assessment of benthic community is a vital component for
      that interpretation, yet their evaluation is complex and requires a large
      expenditure of time and funds. Thus, there is a need for new tools that are less
      expensive and more understandable for managers. This paper presents a benthic
      biotope index to predict from physical and chemical variables the occurrence of
      macrobenthic habitats. Parameters such as sediment type, organic matter, depth,
      and hydrodynamic parameters were selected, through a discriminant analysis, to
      compute the index. Other authors have used multivariate methods to determine the
      benthic biotopes for Sado Estuary. The index proved to be a valid tool to
      classify and assess the spatial patterns of benthic habitat and to synthesize
      stress biotope gradients.

PMID- 15950275
TI  - Study of graft copolymerization of N-maleamic acid-chitosan and butyl acrylate by
      gamma-ray irradiation.
AB  - N-maleamic acid-chitosan was synthesized and characterized by Fourier transform
      infrared spectra analysis (FT-IR) and 1H NMR. The graft copolymerization of N
      maleamic acid-chitosan and butyl acrylate (BA) in acetic acid aqueous solution
      was investigated, using the gamma-ray of 60Co gamma-irradiation method. DSC
      (differential scanning calorimetry) trace of N-maleamic acid-chitosan-g-PBA has a
      glass-transition temperature (Tg) at -42 degrees C. The thermal stabilities of
      the graft copolymer were studied by the thermal gravimetric analysis (TGA). The
      effect of synthesis variables in the graft copolymerization have been discussed
      in the light of grafting efficiency, grafting percentage, and homopolymer
      percentage. Increasing grafting percentage was observed when the monomer
      concentration and total dose were increased or when the reaction temperature was
      decreased.

PMID- 15950276
TI  - The effect of cyclo-DfKRG peptide immobilization on titanium on the adhesion and
      differentiation of human osteoprogenitor cells.
AB  - This study takes place in the field of development of a bioactive surface of
      titanium alloys. In this paper, titanium was functionalized with cyclo-DfKRG
      peptide by coating or grafting using different anchors (thiol or phosphonate) as
      spacers between the surface and the peptide. Cell adhesion, and differentiation
      of human osteoprogenitor (HOP) cells arising from human bone marrow were
      investigated. Our results seem to demonstrate that cyclo-DfKRG peptide coating
      with a phosphonate anchor and grafting procedure contributes to higher cell
      adhesion and a strong ALP and Cbfa1 mRNA expression, after 10 days of cell
      seeding. At the contrary, this peptide coated with a thiol anchor stimulates
      differentiation of HOP within 3 days of culture.

PMID- 15950277
TI  - A silanized hydroxypropyl methylcellulose hydrogel for the three-dimensional
      culture of chondrocytes.
AB  - Articular cartilage has limited intrinsic repair capacity. In order to promote
      cartilage repair, the amplification and transfer of autologous chondrocytes using
      three-dimensional scaffolds have been proposed. We have developed an injectable
      and self-setting hydrogel consisting of hydroxypropyl methylcellulose grafted
      with silanol groups (Si-HPMC). The aim of the present work is to assess both the
      in vitro cytocompatibility of this hydrogel and its ability to maintain a
      chondrocyte-specific phenotype. Primary chondrocytes isolated from rabbit
      articular cartilage (RAC) and two human chondrocytic cell lines (SW1353 and
      C28/I2) were cultured into the hydrogel. Methyl tetrazolium salt (MTS) assay and
      cell counting indicated that Si-HPMC hydrogel did not affect respectively
      chondrocyte viability and proliferation. Fluorescent microscopic observations of
      RAC and C28/I2 chondrocytes double-labeled with cell tracker green and ethidium
      homodimer-1 revealed that chondrocytes proliferated within Si-HPMC. Phenotypic
      analysis (RT-PCR and Alcian blue staining) indicates that chondrocytes, when
      three-dimensionnally cultured within Si-HPMC, expressed transcripts encoding type
      II collagen and aggrecan and produced sulfated glycosaminoglycans. These results
      show that Si-HPMC allows the growth of differentiated chondrocytes. Si-HPMC
      therefore appears as a potential scaffold for three-dimensional amplification and
      transfer of chondrocytes in cartilage tissue engineering.

PMID- 15950278
TI  - Mechanism of bone incorporation of beta-TCP bone substitute in open wedge tibial
      osteotomy in patients.
AB  - A histological study was performed of bone biopsies from 16 patients (17
      biopsies) treated with open wedge high tibial osteotomies for medial knee
      osteoarthritis. The open wedge osteotomies were filled with a wedge of
      osteoconductive beta tricalcium phosphate (beta-TCP) ceramic bone replacement. At
      the time of removal of the fixation material, core biopsies of the area where the
      beta-TCP was located were taken at different follow-up periods (6-25 months).
      beta-TCP resorption, bone ingrowth and bone remodelling were studied. We
      hypothesized that the incorporation and remodelling process occurs similarly as
      in animals. Histology showed a good resorption of the beta-TCP with complete
      incorporation and remodelling into new bone. The different phases as described in
      animal studies were found. A correlation was found between histological findings
      and radiological assessment. In conclusion, beta-TCP appeared to be a bone
      replacement material with optimal biocompatibility, resorption characteristics
      and bone conduction properties for the clinical use.

PMID- 15950279
TI  - Direct micro-patterning of biodegradable polymers using ultraviolet and
      femtosecond lasers.
AB  - Thin films of biodegradable polymeric materials, poly(epsilon-caprolactone) (PCL)
      and poly(glycolic acid) (PGA) were micro-patterned using a Ti-sapphire
      femtosecond pulsed laser and ArF excimer UV laser in ambient conditions. The
      laser-patterned polymers were characterized using a scanning electron microscope
      (SEM), Fourier transform infrared spectroscopy in attenuated total reflectance
      mode (FTIR-ATR) and X-ray photoelectron spectroscopy (XPS). In-vitro degradation
      tests were performed and the laser-patterned samples showed to be within one
      standard deviation of the control samples. Our results demonstrate that both
      lasers are excellent tools for micro-patterning biodegradable polymers since the
      bulk properties of the material can remain intact and because the direct-write
      method is rapid, flexible, and a chemical-free process.

PMID- 15950280
TI  - Bi-potential behaviour of cytotrophoblasts in first trimester chorionic villi.
AB  - Murine trophoblast stem (TS) cells express fibroblast growth factor receptor 2
      (FGFR2) and are maintained in their proliferative state by fibroblast growth
      factor 4 (FGF4). We show in this report that in the first trimester human
      placenta FGFR2 expression is similarly found in a subset of villous
      cytotrophoblast and in proximal anchoring columns. Western analysis demonstrated
      declining FGFR2 protein expression as gestation advanced, suggesting a similar
      role for FGF in early human trophoblast proliferation. Mouse TS cell
      differentiation is known to occur along two distinct transcriptionally-regulated
      pathways; extravillous trophoblast (EVT) cells invade the uterine wall to promote
      maternal blood flow whilst syncytiotrophoblast lines chorionic villi in the
      labyrinth. Similar differentiation steps occur in the human placenta though the
      fate of human trophoblast stem cells is presently unknown. To investigate the
      mechanisms underlying human cytotrophoblast differentiation we have developed a
      novel cultured floating first trimester villous explant model in which denuded
      first trimester villi spontaneously regenerate syncytiotrophoblast following 48 h
      of culture. Addition of FGF4 and heparin inhibited syncytiotrophoblast
      regeneration in favor of forming clumps of cytotrophoblast. Proximal cells in
      these clumps were FGFR2 immuno-reactive and proliferative, intermediate parts
      expressed alpha5beta1-integrin, while the distal portion expressed HLA-G and the
      invasive integrin alpha1beta1 indicating differentiation to the EVT phenotype. In
      contrast, non-denuded villi exposed to FGF4 exhibited similar proliferation of
      the cytotrophoblast; however, these cells did not express any of the invasive EVT
      markers. We conclude that FGFR2-positive chorionic cytotrophoblasts exhibit bi
      potential behaviour, being capable of forming either syncytiotrophoblast or EVT.
      We suggest bipotential trophoblast progenitor cells persist during first
      trimester human placental development.

PMID- 15950281
TI  - Factors related to suicide in New York state prisons.
AB  - OBJECTIVE: Examine factors related to prison suicides to aid prevention. METHOD:
      Review the mental health records of all 76 suicides that occurred between 1993
      and 2001 in New York State Department of Correctional Services (NYSDOCS) prisons
      that had some contact with mental health services during their incarceration.
      (This represented 84% of all NYSDOCS suicides.) Extract data from the
      psychological autopsies for a sample of 40 of these suicides. RESULTS: Of the
      suicide victims with some mental health contact, 95% had a substance abuse
      history, 70% displayed agitation or anxiety prior to the suicide, and 48% had a
      behavioral change. Common stressors preceding the suicide were inmate-to-inmate
      conflict (50%), recent disciplinary action (42%), fear (40%), physical illness
      (42%), and adverse information (65%) such as loss of good time or disruption of
      family/friendship relationships in the community. Forty-one percent had received
      a mental health service within 3 days of the suicide. Compared to the about 7200
      inmates actively receiving mental health services in state prison, African
      Americans and patients with a Major Mood (Bi-polar or Major Depression) were
      under-represented. Adjustment Disorder, Schizophrenia, and Personality Disorder
      diagnoses were over-represented. Suicide victims were more likely to have been
      incarcerated for a violent crime. CONCLUSION: Mental illness, anxiety/agitation,
      behavior change, stressors, history of substance abuse, and non-African-American
      were important risk factors.

PMID- 15950282
TI  - Evaluation of a cognitive-behavioral program for chronically psychotic forensic
      inpatients.
AB  - The present study evaluated the progress of four groups of chronically psychotic
      patients in treatment at De Kijvelanden Forensic Psychiatric Hospital. The
      psychotic patients were offered a cognitive-behavioral program, including psycho
      education, grief processing, stress management, functional training, coping with
      psychotic symptoms (Liberman module) and social skills training. Nine patients
      dropped out of the program. Sixteen patients who completed it scored
      significantly better than a control group of 16 psychotic patients, who had not
      yet participated in the program, on the "social skills" and "negative coping
      behavior" subscales of one of two observation scales used. On the other
      observation instrument (REHAB), however, no significant improvement in the
      general level of functioning was found in the group of treated patients, as
      compared to the control group. Apart from these two observation scales, the PANSS
      (structured interview for positive, negative and general psychopathological
      symptoms) and the SIG (self-report questionnaire for social anxiety and social
      responses) were used to evaluate treatment progress. Significant improvements
      were not found on these scales, except for a slight positive effect on the PANSS
      negative symptoms scale. These results illustrate the difficulties and
      limitations of treating chronically psychotic offenders, who often also suffer
      from cluster B personality disorders.

PMID- 15950284
TI  - Coronal or swinging eyelid decompression for patients with disfiguring proptosis
      in Graves' orbitopathy? Comparison of results in one center.
AB  - PURPOSE: To compare 2 different approaches for 3-wall orbital decompression in
      patients with disfiguring proptosis due to Graves' orbitopathy, and to determine
      which technique is preferable. DESIGN: Retrospective nonrandomized study with a
      concurrent comparison group. PARTICIPANTS: Charts of 74 consecutive patients with
      disfiguring proptosis due to Graves' orbitopathy who underwent coronal (46) or
      swinging eyelid (28) decompression between January 1, 2000 and January 1, 2004
      were studied retrospectively. Patients with dysthyroid optic neuropathy were
      excluded. METHODS: We analyzed the following parameters: proptosis reduction,
      ocular motility, number of additional operations, number and kind of
      complications, patients' satisfaction, patients' estimation of numbness or
      abnormal sensations in the field of operation and surgical scars, and duration of
      hospitalization time. MAIN OUTCOME MEASURES: Reduction of proptosis, changes in
      eye motility, and duration of hospitalization. RESULTS: Mean proptosis reductions
      were 4.8 mm (range, 1-11) after coronal decompression and 5.6 mm (range, 0-8)
      after swinging eyelid decompression (P = 0.025). Patients who were operated by
      the swinging eyelid approach had no more deteriorated motility and a shorter
      hospitalization time. Complications were seen rarely. Both groups of patients
      showed high satisfaction scores. CONCLUSION: Relative to the coronal approach,
      swinging eyelid decompression results in at least the same proptosis reduction,
      no greater motility disturbance, and a shorter hospitalization time.

PMID- 15950285
TI  - Kv2.1: a voltage-gated k+ channel critical to dynamic control of neuronal
      excitability.
AB  - Neurons use a variety of mechanisms to dynamically control their own signaling
      capabilities. Regulation of voltage-dependent K+ channel localization and
      function has long been recognized as a major mechanism to achieve dynamic
      regulation of intrinsic neuronal excitability in a number of mammalian and non
      mammalian neurons. Our recent evidence, together with compelling data from other
      laboratories, suggests that in mammalian neurons the Kv2.1 channel may play an
      especially prominent role in determining intrinsic neuronal excitability. Kv2.1
      is widely expressed in brain and composes the majority of delayed rectifier K+
      current in pyramidal neurons in cortex and hippocampus, and is also widely
      expressed in interneurons. Dynamic modulation of Kv2.1 localization and function
      by a mechanism involving activity-dependent Kv2.1 dephosphorylation dramatically
      impacts intrinsic excitability of neurons. Here we review previous studies of
      Kv2.1 localization and function in neurons, and summarize recent work regarding
      dynamic regulation of these characteristics. We also discuss possible roles of
      the Kv2.1 channel in neuronal and network excitability.

PMID- 15950283
TI  - Expression of the MHC class II transactivator (CIITA) type IV promoter in B
      lymphocytes and regulation by IFN-gamma.
AB  - The MHC class II transactivator (CIITA), the master regulator of MHC class II
      (MHC II) expression, is a co-activator that controls MHC II transcription. Human
      B lymphocytes express MHC II constitutively due to persistent activity of CIITA
      promoter III (pIII), one of the four potential promoters (pI-pIV) of this gene.
      Although increases in MHC II expression in B cells in response to cytokines have
      been observed and induction of MHC II and CIITA by IFN-gamma has been studied in
      a number of different cell types, the specific effects of IFN-gamma on CIITA
      expression in B cells have not been studied. To investigate the regulation of
      CIITA expression by IFN-gamma in B cells, RT-PCR, in vivo and in vitro
      protein/DNA binding studies, and functional promoter analyses were performed.
      Both MHC II and CIITA type IV-specific RNAs increased in human B lymphocytes in
      response to IFN-gamma treatment. CIITA promoter analysis confirmed that pIV is
      IFN-gamma inducible in B cells and that the GAS and IRF-E sites are necessary for
      full induction. DNA binding of IRF-1 and IRF-2, members of the IFN regulatory
      factor family, was up-regulated in B cells in response to IFN-gamma and increased
      the activity of CIITA pIV. In vivo genomic footprint analysis demonstrated
      proteins binding at the GAS, IRF-E and E box sites of CIITA pIV. Although CIITA
      pIII is considered to be the hematopoietic-specific promoter of CIITA, these
      findings demonstrate that pIV is active in B lymphocytes and potentially
      contributes to the expression of CIITA and MHC II in these cells.

PMID- 15950286
TI  - The role of phospholipid methylation in 1-methyl-4-phenyl-pyridinium ion (MPP+)
      induced neurotoxicity in PC12 cells.
AB  - Excessive methylation has been proposed to be involved in the pathogenesis of
      Parkinson's disease (PD), via mechanisms that involve phospholipid methylation.
      Meanwhile, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was found to
      stimulate phospholipid methylation via the oxidized metabolite, 1-methyl-4-phenyl
      pyridinium (MPP+), in the rat brain and liver tissues. In the present study, we
      investigated the effect of MPP+ on phosphatidylethanolamine N-methyltransferases
      (PENMT) and the potential role of this pathway in MPP(+)-induced neurotoxicity
      using PC12 cells. The results obtained indicate that MPP+ stimulated
      phosphatidylethanolamine (PTE) methylation to phosphatidylcholine (PTC) and
      correspondingly increased the formation of lysophosphatidylcholine (lyso-PTC).
      Moreover, the addition of S-adenosylmethionine (SAM) to the cell culture medium
      increases MPP(+)-induced cytotoxicity. The incubation of 1mM MPP+ and various
      concentrations of SAM (0-4 mM) decreased the viability of PC12 cells from 80%
      with MPP+ alone to 38% viability with 4 mM SAM for 4 days incubation. The data
      also revealed that the addition of S-adenosylhomocysteine (SAH), a methylation
      inhibitor, offered significant protection against MPP(+)-induced cytotoxicity,
      indicating that methylation plays a role in MPP(+)-induced cytotoxicity.
      Interestingly, lyso-PTC showed similar actions to MPP+ in causing many cytotoxic
      changes with at least 10 times higher potency. Lyso-PTC induced dopamine release
      and inhibited dopamine uptake in PC12 cells. Lyso-PTC also caused the inhibition
      of mitochondrial potential and increased the formation of reactive oxygen species
      in PC12 cells. These results indicate that phospholipid methylation pathway might
      be involved in MPP+ neurotoxicity and lyso-PTC might play a role in MPP(+)
      induced neurotoxicity.

PMID- 15950287
TI  - Reduction of zinc-positive terminal fields in striatum of mouse after 1-methyl-4
      phenylpyridinium neurotoxicity.
AB  - Zinc is an essential trace element in the central nervous system and is located
      in three distinct pools: free zinc, vesicular zinc and protein-bound zinc. Zinc
      may serve as an endogenous neuromodulator and has been associated with
      neuropathologies. This study was undertaken to determine whether levels of
      vesicular zinc in neuronal terminals would decrease in response to the
      dopaminergic neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+). Adult male C-57
      black mice were injected with MPP+ (0.72 mg/kg) into their right lateral
      ventricle. All animals were killed at 1, 2, 24 h and 7 days after MPP+ or saline
      administration. The brains were stained for zinc sulfides and the density of zinc
      positive terminal fields was evaluated after MPP+ administration. The relative
      optical density analysis of zinc-positive terminal fields showed significant
      decreases in the striatum at 1, 2 and 24 h (24, 18 and 14%, respectively, versus
      control) and ventricular epithelium (1, 2, 24 h and 7 days). The hippocampus
      showed increase in the stratum oriens and stratum radiatum at different times.
      MPP+ administration reduced dopamine levels at 24h and 7 days (36 and 40%,
      respectively, versus control) as a result of the neurotoxic action of MPP+. The
      decrease of zinc-positive neuronal terminal fields in the striatum after MPP+
      administration is most likely due to a neuronal release of vesicular zinc in
      response to its dopaminergic neurotoxicity.

PMID- 15950288
TI  - Trends in anti-bacterial resistance among Streptococcus pneumoniae isolated in
      the USA, 2000-2003: PROTEKT US years 1-3.
AB  - OBJECTIVES: To determine geographic and temporal trends in anti-bacterial
      resistance among Streptococcus pneumoniae isolated from patients with respiratory
      tract infections as part of the PROTEKT US surveillance study (2000-2003).
      METHODS: From 2000 to 2003, 31 001 isolates of S. pneumoniae were collected. Anti
      bacterial minimum inhibitory concentrations were determined at a central
      laboratory using the CLSI broth microdilution method. Macrolide resistance
      genotypes were determined by PCR. RESULTS: Overall, 29.4, 22.5, 0.9, and 0.02% of
      S. pneumoniae isolates were resistant to erythromycin, penicillin, levofloxacin,
      and telithromycin, respectively, with considerable regional variability.
      Multidrug resistance was stable at approx. 31%. Among macrolide-resistant
      isolates, mef(A) was the most prevalent resistance gene identified; however, the
      percentage of isolates with this gene decreased from 68.8% (2000) to 63.9%
      (2003), while the prevalence of isolates containing both the erm(B) and mef(A)
      genes increased (2000, 9.7%; 2003, 16.4%). Over 90% of these erm(B)+mef(A)
      positive isolates were also resistant to penicillin, tetracycline, or
      trimethoprim-sulfamethoxazole, while 98.6% were susceptible to levofloxacin and
      99.1% were susceptible to telithromycin. CONCLUSIONS: Penicillin and erythromycin
      resistance among isolates of S. pneumoniae from the U.S.A. remained high over the
      3 years of the study. Telithromycin demonstrated potent in vitro activity against
      pneumococcal strains.

PMID- 15950289
TI  - Insulin-like growth factor I treatment for cerebellar ataxia: addressing a common
      pathway in the pathological cascade?
AB  - In the present work we review evidence supporting the use of insulin-like growth
      factor I (IGF-I) for treatment of cerebellar ataxia, a heterogeneous group of
      neurodegenerative diseases of low incidence but high societal impact. Most types
      of ataxia display not only motor discoordination, but also additional
      neurological problems including peripheral nerve dysfunctions. Therefore, a
      feasible therapy should combine different strategies aimed to correct the various
      disturbances specific for each type of ataxia. For cerebellar deficits, and most
      probably also for other types of brain deficits, the use of a wide-spectrum
      neuroprotective factor such as IGF-I may prove beneficial. Intriguingly, both
      ataxic animals as well as human patients show altered serum IGF-I levels. While
      the pathogenic significance of IGF-I, if any, in this varied group of diseases is
      difficult to envisage, disrupted IGF-I neuroprotective signaling may constitute a
      common stage in the pathological cascade associated to neuronal death. Indeed,
      treatment with IGF-I has proven effective in animal models of ataxia. Based on
      this pre-clinical evidence we propose that IGF-I should be tested in clinical
      trials of cerebellar ataxia in those cases where either serum IGF-I deficiency
      (as in primary cerebellar atrophy) or loss of sensitivity to IGF-I (as in ataxia
      telangiectasia) has been reported. Taking advantage of the widely protective and
      anabolic actions of IGF-I on peripheral tissues, this neurotrophic factor may
      provide additional therapeutic advantages for many of the disturbances commonly
      associated to ataxia such as cardiopathy, muscle wasting, or immune dysfunction.

PMID- 15950291
TI  - Antibodies which block anti-myelin basic protein antibodies associated with
      development of experimental autoimmune encephalomyelitis in Wistar rats.
AB  - OBJECTIVE: In sera from normal rats and from rats injected with whole myelin in
      complete Freund adjuvant to induce EAE we study the presence of antibodies
      capable to inhibit the reactivity of autoantibodies directed to myelin basic
      protein (MBP). METHODS: Sera from rats that developed or not clinical signs of
      EAE were obtained previously to immunization, at acute stage of the disease and
      when the animals were completely recuperated, and chromatographied on a protein G
      Sepharose column to obtain the retained (IgG) fractions. Then these fractions
      were depleted of anti-MBP reactivity by affinity chromatography and the ability
      of these depleted sera to block the reactivity of anti-MBP IgG antibodies was
      analyzed by an immunoblot technique. RESULTS: IgG fractions from preimmune sera
      inhibited the anti-MBP IgG reactivity associated to EAE. The analysis of sick EAE
      animals showed that the inhibitory activity faded away with the onset of the
      clinical signs but returned at its maximum value during the spontaneous
      remission. Animals that never developed clinical EAE did not show changes in the
      level of inhibitory activity that was similar to that observed in the preimmune
      sera. CONCLUSIONS: The presence of IgG antibodies blocking the anti-MBP IgG
      reactivity correlates with the development of the clinical signs of EAE.

PMID- 15950290
TI  - Abnormal development of zinc-containing cortical circuits in the absence of the
      transcription factor Tailless.
AB  - Absence of the transcription factor tailless (tlx) leads to premature laminar
      development and thinning of neocortex. We used zinc autometallography to
      determine if tailless deletion alters the organization of cortical circuits. In
      tlx-/- mice, layer 4 barrels, which normally lack synaptic zinc, are densely
      innervated by zinc-containing terminals. Furthermore, barrels with zinc inputs
      are constructed, in part, from zinc-sequestering neurons, a phenotype not
      normally found in layer 4.

PMID- 15950292
TI  - Management of pediatric hemoptysis: review and a case of isolated unilateral
      pulmonary artery agenesis.
AB  - OBJECTIVES: Management of hemoptysis in the pediatric patient requires an
      otolaryngologist knowledgeable and skilled in the causes and management of this
      potentially life-threatening condition. This paper will discuss the management of
      pediatric hemoptysis by the otolaryngologist through an index case of massive
      hemoptysis seen in a child with isolated unilateral pulmonary artery agenesis
      (IUPAA). STUDY DESIGN: Literature review and index case. METHODS: Through a
      Medline search and the experience of the author (A.J.M.), we reviewed the causes
      and treatment options for hemoptysis in the pediatric patient. RESULTS:
      Management of hemoptysis by the otolaryngologist requires prompt diagnosis and
      patient stabilization. This allows the patient access to multiple treatment
      options which may include diagnostic or therapeutic bronchoscopy, angiography
      with embolization, and surgical intervention such as resection or
      revascularization. IUPAA is an unusual, and potentially life-threatening cause of
      hemoptysis in the pediatric patient. CONCLUSION: Hemoptysis in the pediatric
      patient requires prompt and thorough evaluation and treatment. An approach for
      the management of pediatric hemoptysis, including massive hemoptysis, is
      described.

PMID- 15950293
TI  - Use of lyophilized standards for the calibration of a newly developed real time
      PCR assay for human herpes type six (HHV6) variants A and B.
AB  - A quantitative real time PCR assay utilizing an Eclipse minor groove binding
      hybridization probe was developed to detect and type human herpes 6. A 115 base
      pair product from the U67 gene was selected for amplification and the assay
      included a noncompetitive internal control. The probe's melting temperature from
      the amplified sequence differentiated between HHV6 variants (A and B). In this
      study, 120 samples (60 spiked and 60 negative) comprising CSF, plasma, and serum
      were tested at high and medium levels, and near the limit of quantitation. The
      use of stored standard curves for assay calibration was compared to curves run on
      each assay, and the stability of liquid frozen versus lyophilized frozen stocks
      for calibrators and controls was assessed. After 9 months of clinical testing,
      assay performance was examined to determine the percent positive rate and
      positive sample reproducibility, as well as to evaluate standard curve stability.
      We obtained 100% correlation to expected results for positive and negative
      samples. A stored curve proved easier, more cost effective, and more reliable
      than running a standard curve on each assay. The use of lyophilized standards
      contributes substantially to the maintenance of reproducible testing over an
      extended period of time.

PMID- 15950294
TI  - Simultaneous detection of two major lamivudine-resistant mutants using
      competitively differentiated-PCR.
AB  - Rapid, specific and sensitive methods without advanced equipment are required
      urgently in developing countries in order to detect or monitor lamivudine
      resistant mutants routinely before or in the course of the therapy. A protocol is
      described for the detection of two major YMDD mutations simultaneously through
      modifying a previous competitively differentiated-PCR (CD-PCR) by revising the
      strategy, increasing the number of competitively differentiated primers,
      increasing the number of labeled haptens, optimizing the amplification system and
      analyzing its products by enzyme immunoassay. Special care was taken to promote
      the sensitivity, specificity and the ability of the protocol to detect mutation
      in mixture of the mutants and wild strain. YMDD mutants in clinical serum samples
      were detected simultaneously, specifically and rapidly only with assistance of
      the equipment used widely in highly prevalent areas of hepatitis B virus
      infection.

PMID- 15950295
TI  - cDNA cloning and regulation of two sex-hormone-repressed hamster tear lipocalins
      having homology with odorant/pheromone-binding proteins.
AB  - A major 20-kDa protein is female-specifically expressed in exorbital lacrimal
      gland (LG) of hamsters and secreted in tears. Here, we identify this female
      specific LG protein (FLP) as a lipocalin, having 85% protein sequence identity
      with male-specific submandibular salivary gland proteins (MSP) secreted in saliva
      and urine of male hamsters. MSP is also female-specifically expressed in LG and
      secreted in tears but FLP was undetectable in submandibular gland (SMG). FLP and
      MSP have similar sex-hormonal regulation in LG, which is different from
      regulation of MSP in SMG. Female-specific expression of FLP and MSP in LG is due
      to their incomplete repression by endogenous estrogens and gonadectomy in both
      sexes and lactation in females resulted in their marked induction, which was
      prevented by estrogen or androgen treatment. FLP and MSP show best sequence
      identity with odorant/pheromone-binding lipocalins (58-29%). Maximum identity
      (58%) is with rat odorant-binding protein (OBP) expressed in lateral nasal
      glands, followed by aphrodisin of hamster vaginal discharge (39%). Cognate
      transcript and a cross-reacting 20-kDa protein were detected in nasal glands of
      rat in both sexes but not in hamsters. Results suggest that two closely related
      lipocalin genes encode FLP and MSP, which are evolutionarily closer to rat OBP
      than to hamster aphrodisin and these have evolved different tissue-specificity
      and sex-hormonal regulation. Possible functions for FLP and MSP are suggested,
      considering their homology to odorant/pheromone-binding lipocalins, their
      presence in tears, saliva and urine as well as their sex-specific and lactation
      induced expression.

PMID- 15950296
TI  - Microtubule plus ends, motors, and traffic of Golgi membranes.
AB  - The intimate link between microtubule (MT) organization and the components of the
      secretory pathway has suggested that MT-based motility is an essential component
      of vesicular membrane transport and membrane polarization. The molecular details
      of these processes are still under investigation; however, a novel class of MT
      plus end-binding proteins shed new light on transport between the endoplasmic
      reticulum (ER) and Golgi apparatus. The dynactin complex, an initial member of
      this family, shares localization and live-cell imaging phenotypes with other plus
      end-binding proteins such as CLIP-170 and EB1. In addition, dynactin has been
      shown to mediate the binding of ER-Golgi transport vesicles to MTs through a
      regulated MT-binding motif in p150(Glued). Whereas the plus end-binding activity
      of CLIP-170 and EB1 has been linked to the regulation of dynamic instability, the
      plus end binding of dynactin is implicated in a search-capture mechanism for
      dynein-dependent cargoes. An examination of dynactin's role in ER-Golgi transport
      suggests that plus end binding could be a reflection of fundamental membrane
      transport mechanisms.

PMID- 15950297
TI  - Genomic analysis of the protein secretion systems in Clostridium acetobutylicum
      ATCC 824.
AB  - Consistent information about protein secretion in Gram-positive bacteria is
      essentially restricted to the model organism Bacillus subtilis. Among genome
      sequenced clostridia, Clostridium acetobutylicum has been the most extensively
      studied from a physiological point of view and is the organism for which the
      largest variety of molecular biology tools have been developed. Following in
      silico analyses, both secreted proteins and protein secretion systems were
      identified. The Tat (Twin arginine translocation; TC #2.A.64) pathway and ABC
      (ATP binding cassette) protein exporters (TC #3.A.1.) could not be identified,
      but the Sec (secretion) pathway (TC #3.A.5) appears to be used prevalently.
      Similarly, a flagella export apparatus (FEA; TC #3.A.6.), holins (TC #1.E.), and
      an ESAT-6/WXG100 (early secreted antigen target of 6 kDa/proteins with a WXG
      motif of approximately 100 residues) secretion system were identified. Here, we
      report for the first time the identification of a fimbrilin protein exporter
      (FPE; TC #3.A.14) and a Tad (tight adherence) export apparatus in C.
      acetobutylicum. This investigation highlights the potential use of this
      saprophytic bacterium in biotechnological and biomedical applications as well as
      a model organism for studying protein secretion in pathogenic Gram-positive
      bacteria.

PMID- 15950298
TI  - The new definition of myocardial infarction and the impact of troponin
      determination on clinical practice.
AB  - OBJECTIVE: To discuss the more controversial clinical and laboratory aspects in
      the application of the new biochemical diagnostic standard for myocardial
      infarction, 4 years after its introduction, and to make some suggestions, which
      could allow for a more realistic application of the new definition in the current
      clinical practice. METHODS: Studies published in the last 4 years in the most
      important cardiology and laboratory medicine journals (including proceedings of
      the international meetings), discussing advantages and limits of the new
      definition of myocardial infarction, were reviewed and pertinent data were
      discussed and compared with similar information available in literature. RESULTS
      AND CONCLUSIONS: Although the exact status of implementation of the new
      definition of myocardial infarction cannot yet be known, the trend toward such
      recommendation is evolving significantly, even if at different rates in different
      countries. To make the transition smoother, major educational efforts are
      required to disseminate the conceptual reasoning behind the new guidelines. On
      the other hand, more knowledge is needed for some relevant issues, such as the
      different analytical performance of cardiac troponin assays or the prognostic
      significance of biomarker changes after a percutaneous coronary intervention.

PMID- 15950299
TI  - Levosimendan reduces plasma amino terminal proBNP in patients with decompensated
      heart failure.

PMID- 15950300
TI  - Surgical repair of post-infarction ventricular septal defect: 19 years of
      experience.
AB  - OBJECTIVES: To review our experience of surgical repair of post-infarction
      ventricular septal defect (VSD). METHODS: In the period 1983-2002, 50 patients
      underwent repair of VSD. Mean age was 66 years, male sex 52%. Infarct location
      was anterior in 60% and posterior in 40% of cases. Median interval between
      rupture and surgery was 2 days. Preoperative intra-aortic balloon
      counterpulsation was employed in 56%; a coronary angiogram was performed in 98%
      of cases. A patch repair technique was used in 90% of cases. Coronary bypass
      grafting was associated in 50% of patients. RESULTS: Mean aortic clamp time was
      101+/-31 min. Global operative mortality was 36%, respectively 26.7% in anterior
      and 50% in posterior location (p=ns). Emergency operation and interval from
      rupture to surgery less than 3 days were univariate predictor of early mortality.
      Five years survival excluding operative deaths was 76%. CONCLUSIONS: The surgical
      repair of post-infarction VSD entails a high operative mortality; different
      techniques were employed with similar results. Emergency operation is associated
      with a worse short-term prognosis; long-term survival is acceptable.

PMID- 15950301
TI  - Third party purchasing of health services: patient choice and agency.
AB  - Health care provision is almost universally characterised by third party
      purchasing in which the provider of health services is reimbursed by an agency
      (public or private insurer), rather than the patient. We show how a purchaser can
      manage the incentives that patient choice gives rise to by its own choice of
      monitoring arrangement. Even though patients are ignorant about their exact
      medical conditions and insulated from the costs of health care, they can help
      alleviate incentive problems due to asymmetric information through the choices
      that they make about whether to be treated. We show that if patients are
      responsive to variations in treatment, it can be worthwhile to base payment on
      the health outcome achieved rather than upon the treatment delivered. Outcomes
      based payments may also be preferable where services are supplied by not-for
      profit agencies who are intrinsically concerned with patient welfare.

PMID- 15950302
TI  - Listening to the brain: microelectrode biosensors for neurochemicals.
AB  - Chemical signalling underlies every function of the nervous system, from those of
      which we are unaware, for example, control of the heart, to higher cognitive
      functions, such as emotions, learning and memory. Neurotransmitters and
      neuromodulators mediate communication between neurons and between neurons and non
      neural cells such as glia and muscle. In the past, the means for studying the
      production and release of these signalling agents directly has been limited in
      its temporal and spatial resolution relative to the dynamics of chemical
      signalling and the structures of interest in the brain. Now microelectrode
      biosensors are becoming available that give unprecedented spatial and temporal
      resolution, enabling, for the first time, direct measurement in real time of the
      chemical conversations between cells in the nervous system.

PMID- 15950303
TI  - Pathways to the analysis of microarray data.
AB  - The development of microarray technology allows the simultaneous measurement of
      the expression of many thousands of genes. The information gained offers an
      unprecedented opportunity to fully characterize biological processes. However,
      this challenge will only be successful if new tools for the efficient integration
      and interpretation of large datasets are available. One of these tools, pathway
      analysis, involves looking for consistent but subtle changes in gene expression
      by incorporating either pathway or functional annotations. We review several
      methods of pathway analysis and compare the performance of three, the binomial
      distribution, z scores, and gene set enrichment analysis, on two microarray
      datasets. Pathway analysis is a promising tool to identify the mechanisms that
      underlie diseases, adaptive physiological compensatory responses and new avenues
      for investigation.

PMID- 15950305
TI  - Electrophysiology in attention-deficit/hyperactivity disorder.

PMID- 15950304
TI  - Attention deficit and impulsivity: selecting, shifting, and stopping.
AB  - The present selective review addresses attention, inhibition, and their
      underlying brain mechanisms, especially in relation to attention
      deficit/hyperactivity disorders (AD/HD), and the effects of methylphenidate. In
      particular, event-related potential (ERP) studies suggest a deficit in the early
      filtering aspect of selective attention in children with AD/HD. Results from stop
      tasks are consistent with impairments in stopping performance in AD/HD, but in
      children (as opposed to adults) these effects cannot be easily dissociated from
      more general impairments in attention to the task, and therefore an
      interpretation in terms of inhibitory control is not straightforward. On the
      other hand, the beneficial effects of methylphenidate are more specific to
      stopping, and there are no clearcut effects of methylphenidate on measures of
      selective attention. Even when group differences pertain specifically to stopping
      performance (as with adults with AD/HD), ERP evidence suggests at least a partial
      contribution of differences in switching attention to the stop signal, as
      revealed in measures of sensory cortex activation. ERP evidence from cued go/nogo
      tasks underlines the importance of taking into account the contribution of higher
      order control processes involved in anticipation of and preparation for task
      stimuli. It suggests that in certain conditions, expectancy, rather than response
      bias, contributes to increased behavioral response tendencies, and that a
      presumed index of response inhibition, the nogo N2, may rather reflect conflict
      monitoring. In sum, direct reflections of brain activity suggest that mechanisms
      of expectation and attention, rather than of response bias or inhibitory control,
      govern behavioral manifestations of impulsivity.

PMID- 15950306
TI  - Cloning and expression of the malolactic gene of Pediococcus damnosus NCFB1832 in
      Saccharomyces cerevisiae.
AB  - Wine production is characterized by a primary alcoholic fermentation, conducted
      by Saccharomyces cerevisiae, followed by a secondary malolactic fermentation
      (MLF). Although most lactic acid bacteria (LAB) have the ability to metabolize L
      malate, only a few species survive the high ethanol and SO2 levels in wine. Wines
      produced in colder viticultural regions have a lower pH than wines produced in
      warmer regions. The decarboxylation of L-malate in these wines leads to an
      increase in pH, more organoleptic complexity and microbiological stability. MLF
      is, however, difficult to control and problems often occur during filtering of
      such wines. Pediococcus spp. are known to occur in high pH wines and have strong
      malolactic activity. However, some pediococci synthesize exocellular
      polysaccharides, which may lead to abnormal viscosity in wine. In this study, the
      malolactic gene from Pediococcus damnosus NCFB1832 (mleD) was cloned into S.
      cerevisiae and co-expressed with the malate permease gene (mae1) of
      Schizosaccharomyces pombe. Expression of the mleD gene was compared to the
      expression of two other malolactic genes, mleS from Lactococcus lactis MG1363 and
      mleA from Oenococcus oeni Lal1. The genetically modified strain of S. cerevisiae
      decreased the level of L-malate in grape must to less than 0.3 gl(-1) within 3
      days. This is the first expression of a malolactic gene from Pediococcus in S.
      cerevisiae.

PMID- 15950307
TI  - Biodiesel production from triolein and short chain alcohols through biocatalysis.
AB  - Oleic acid alkyl esters (biodiesel) were synthesised by biocatalysis in solvent
      free conditions. Different commercial immobilised lipases, namely Candida
      antarctica B, Rizhomucor miehei, and Pseudomonas cepacia, were tested towards the
      reaction between triolein and butanol to produce butyl oleate. Pseudomonas
      cepacia lipase resulted to be the most active enzyme reaching 100% of conversion
      after 6h. Different operative conditions such as reaction temperature, water
      activity, and reagent stoichiometric ratio were investigated and optimised. These
      conditions were then used to investigate the effect of linear and branched short
      chain alcohols. Methanol and 2-butanol were the worst alcohols: the former,
      probably, due to its low miscibility with the oil and the latter because
      secondary alcohols usually are less reactive than primary alcohols. Conversely,
      linear and branched primary alcohols with short alkyl chains (C(2)--C(4)) showed
      high reaction rate and conversion. A mixture of linear and branched short chain
      alcohols that mimics the residual of ethanol distillation (fusel oil) was
      successfully used for oleic acid ester synthesis. These compounds are important
      in biodiesel mixtures since they improve low temperature properties.

PMID- 15950308
TI  - Surface character of pulp fibres studied using endoglucanases.
AB  - The endoglucanase Cel5A from Trichoderma reesei and an endoglucanase from
      Aspergillus sp. (Novozym 476 from Novozyme A/S) were evaluated as probes for the
      surface properties of soft- and hardwood chemical pulp fibres. The hydrolysis
      time curves were in accordance with a two-phase degradation model described by a
      biexponential function. The kinetic parameters corresponding to the amount of
      fast and slow degraded parts of the substrate correlated to tensile index,
      relative bonded area and z-strength of the paper. All paper properties showing a
      correlation with enzyme kinetic parameters were related to fibre-fibre
      interactions. Fluorescence labelling of the reducing end groups in pulp fibres
      followed by enzyme treatment indicated that the fast substrate class corresponds
      to the population of "loose" cellulose chain ends not tightly associated with the
      bulk cellulose. The correlation between the parameters of enzyme kinetics and
      mechanical properties of the paper produced from the corresponding pulp found in
      this study should allow a rapid evaluation of the raw fibre material used in
      paper making process.

PMID- 15950309
TI  - C-reactive protein level as an independent risk factor of metabolic syndrome in
      the Korean population. CRP as risk factor of metabolic syndrome.
AB  - Interrelationship between C-reactive protein (CRP) and metabolic syndrome (MS)
      was evaluated in a community-based cohort of 9773 Koreans aged 40-69 years.
      Metabolic syndrome was defined by criteria of the National Cholesterol Education
      Program. CRP was measured by validated high-sensitivity assay. The median CRP
      level was 1.4 mg/1, and significantly increased as the number of components of MS
      increased (P trend <0.001). CRP levels were significantly but marginally
      correlated with waist circumference (r=0.18), triglyceride (r=0.14), blood
      pressure (r=0.11), HDL-cholesterol (r=-0.10), and fasting glucose (r=0.09) (all P
      values<0.01). Odds ratios of the highest quartile of CRP for each component of
      MS; i.e., waist circumference, triglyceride, glucose metabolism, blood pressure,
      and HDL-cholesterol were 2.36, 1.79, 1.70, 1.32 and 1.28, respectively. The
      highest quartile of CRP was independently associated with 1.72-fold increased
      risk of MS in our logistic regression model adjusted for age, sex, BMI, and
      smoking. This study demonstrated that CRP is a strong associating factor of MS in
      Korean population. We recommend further evaluation of CRP levels in the other
      Asian ethnic groups to establish biological plausibility as the risk factor for
      MS in all ethnic groups.

PMID- 15950310
TI  - Automated expert multiexponential biomodeling interactively over the Internet.
AB  - DIMSUM, an acronym for DIMension of a SUM of exponentials, is a highly automated
      expert system for fitting multiexponential models of increasing dimension to time
      series data. Up to now, a researcher has needed an individual copy of DIMSUM on
      his or her own computer as well as support to learn how to use it. W3DIMSUM, a
      new implementation of DIMSUM, is web-based, new territory for interactive
      biomodeling, allowing interactive multiexponential model building and model
      discrimination over the Internet. The algorithms used are numerically intensive,
      so we have implemented a distributed system, with numerical processing done on
      our server. Only the user interface is run on the client machine, but users can
      load and save data and results on their machines, facilitated by our use of Java
      WebStart.

PMID- 15950311
TI  - Immunohistochemical distribution of MIZIP and its co-expression with the Melanin
      concentrating hormone receptor 1 in the adult rodent brain.
AB  - We have recently identified a Melanin-concentrating hormone receptor 1
      interacting zinc-finger protein (MIZIP) from a human brain cDNA library. Here, we
      report the generation of a specific antibody against MIZIP and its distribution
      in rodent tissues using immunoblotting and immunohistochemical techniques. MIZIP
      was detected as a 27 kDa protein in brain, liver, and skeletal muscle, and to a
      lower extend, in lung, testis, and heart. Subcellular fractionation of adult
      mouse brain revealed the presence of MIZIP and MCHR1 in the cytoplasmic,
      membrane, and synaptosomal fraction, but not in a postsynaptic density
      preparation. In cultured rat, embryonic hippocampal neurons MIZIP is
      somatodendritically localized. In the adult rodent brain, MIZIP is widely
      distributed. High levels of expression were detected in brain regions involved in
      olfaction, feeding behavior, sensorimotor integration, and learning and memory,
      for example, the olfactory bulb, the olfactory tubercle, the caudate putamen, the
      thalamus and hypothalamus, the nucleus accumbens, the cerebral cortex, the
      hippocampus formation, and the cerebellum. Co-expression of MIZIP and MCHR1 was
      observed, for example, in pyramidal neurons of the cerebral cortex and
      hippocampus, in neurons of the olivary nucleus, lateral hypothalamus, nucleus
      accumbens, caudate putamen, pontine, and mesencephalic trigeminal nucleus.
      However, there are also differences in the expression patterns, for example, high
      expression of MCHR1 was detected in the lateral habenula, but no expression of
      MIZIP. These data support the notion that MIZIP might interact with MCHR1 in a
      cell type specific manner in vivo, suggesting a role in the regulation of MCH
      signalling in distinct regions of the mammalian brain.

PMID- 15950312
TI  - Changes in hippocampal GABAA receptor subunit composition in bipolar 1 disorder.
AB  - Postmortem CNS studies have suggested an uncoupling of the gamma-aminobutyric
      acid (GABA) and benzodiazepine binding sites on the hippocampal GABA(A) receptor
      in schizophrenia. The GABA(A) receptor is an assembly of discrete subunits that
      form a ligand-gated ion channel, the binding characteristics of which are defined
      by receptor subunit composition. Thus, a likely explanation for an uncoupling
      between the GABA and benzodiazepine binding sites on the GABA(A) receptor would
      be a change in receptor subunit composition. To test this hypothesis we measured
      the density of GABA ([(3)H]muscimol) and benzodiazepine ([(3)H]flumazenil)
      binding sites on the GABA(A) receptor in hippocampi, obtained postmortem, from
      schizophrenic, bipolar I disorder and control subjects. In addition, we measured
      the amount of [(3)H]flumazenil binding that could be displaced with zolpidem and
      clonazepam. Levels of both [(3)H]muscimol and [(3)H]flumazenil binding were
      significantly decreased in part of the CA2 from subjects with schizophrenia; the
      decrease in [(3)H]flumazenil being due to decreases in both zolpidem-sensitive
      and -insensitive radioligand binding. There were complex regionally specific
      changes in [(3)H]muscimol binding in the hippocampus from subjects with bipolar I
      disorder but there were no significant changes in the overall levels of
      [(3)H]flumazenil binding. There were significant decreases in zolpidem-sensitive
      and increases in zolpidem-insensitive [(3)H]flumazenil binding in most regions of
      the sections of the hippocampal formation studied in bipolar I disorder. Unlike
      [(3)H]flumazenil, zolpidem does not bind to the alpha5 subunit of the GABA(A)
      receptor; therefore, we postulate that there is an increase in GABA(A) receptors
      containing alpha5 subunit in the hippocampus from subjects with bipolar I
      disorder.

PMID- 15950313
TI  - Bacterial resistance to antibiotics: enzymatic degradation and modification.
AB  - Antibiotic resistance can occur via three general mechanisms: prevention of
      interaction of the drug with target, efflux of the antibiotic from the cell, and
      direct destruction or modification of the compound. This review discusses the
      latter mechanisms focusing on the chemical strategy of antibiotic inactivation;
      these include hydrolysis, group transfer, and redox mechanisms. While hydrolysis
      is especially important clinically, particularly as applied to beta-lactam
      antibiotics, the group transfer approaches are the most diverse and include the
      modification by acyltransfer, phosphorylation, glycosylation, nucleotidylation,
      ribosylation, and thiol transfer. A unique feature of enzymes that physically
      modify antibiotics is that these mechanisms alone actively reduce the
      concentration of drugs in the local environment; therefore, they present a unique
      challenge to researchers and clinicians considering new approaches to anti
      infective therapy. This review will present the current status of knowledge of
      these aspects of antibiotic resistance and discuss how a thorough understanding
      of resistance enzyme molecular mechanism, three-dimensional structure, and
      evolution can be leveraged in combating resistance.

PMID- 15950314
TI  - Biofilms and antibiotic therapy: is there a role for combating bacterial
      resistance by the use of novel drug delivery systems?
AB  - The conventional view of antibiotic resistance is one where bacteria exhibit
      significantly reduced susceptibility to antimicrobials in laboratory tests by
      mechanisms such as altered drug uptake, altered drug target and drug
      inactivation. Whilst these mechanisms undoubtedly make a major contribution to
      antibiotic failure in the clinic, the phenomenon of clinical failure in spite of
      sensitivity in laboratory tests is also well recognised. It is in this context
      that attention has focussed on bacteria growing as adherent biofilms, not only as
      the mode of growth of device-related infections associated for example with
      artificial joints and venous catheters, but also with other chronic infections
      such as those occurring in the respiratory tract. Growth as a biofilm almost
      always leads to a significant decrease in susceptibility to antimicrobial agents
      compared with cultures grown in suspension and, whilst there is no generally
      agreed mechanism for the resistance of biofilm bacteria, it is largely
      phenotypic. That is, when biofilm bacteria are grown in conventional laboratory
      suspension culture they become susceptible to antimicrobials. A number of
      elements in the process of biofilm formation have been studied as targets for
      novel drug delivery technologies. These include surface modification of devices
      to reduce bacterial attachment and biofilm development as well as incorporation
      of antimicrobials-again to prevent colonisation. Electrical approaches have been
      used either to release antimicrobials from device surfaces or to drive
      antimicrobials through the biofilm. Other technologies not specifically focussed
      on biofilms include aerosolized delivery of antibiotics to the lung and
      formulation into liposome and polymer-based vehicles. Liposomal systems have been
      widely studied, either to target antibiotics to the surface of bacterial
      biofilms, or by virtue of their property of being taken up cells of the
      reticuloendothelial system, to target antibiotics towards intracellular bacteria.
      Many polymer-based carrier systems have also been proposed, including those based
      on biodegradable polymers such as poly(lactide-co-glycolide) as well as
      thermoreversible hydrogels. Their contribution to the prevention or resolution of
      infection is reviewed.

PMID- 15950315
TI  - Mutations of the epidermal growth factor receptor gene in atypical adenomatous
      hyperplasia and bronchioloalveolar carcinoma of the lung.
AB  - A hypothesis of multistep carcinogenesis of lung adenocarcinoma from atypical
      adenomatous hyperplasia (AAH) to invasive adenocarcinoma through
      bronchioloalveolar carcinoma (BAC) has been proposed. However, the genetic
      alterations that play a role during these processes are not yet clear. Recently,
      somatic mutations of the epidermal growth factor receptor (EGFR) gene were found
      in lung adenocarcinoma. We examined the status of EGFR mutations in AAH and BAC
      to elucidate the role they play during multistage of lung adenocarcinoma. We
      found somatic EGFR mutations in 3% (1/35) of AAH, 10.8% (4/37) of BAC and 41.9%
      (13/31) of invasive adenocarcinoma. Sixteen of 18 EGFR mutations were found in
      exon 19 and two were in exon 21. Among the 16 EGFR mutations in exon 19, 13 were
      deletions of 15bp and one was an insertion/duplication of 18bp. Mutations of the
      K-ras gene were detected in 26.7% (8/30) of AAH, 16.7% (5/30) of BAC and 10%
      (3/30) of invasive adenocarcinoma. None of the tumors with EGFR mutations had K
      ras mutation simultaneously. Patients who had invasive adenocarcinoma with EGFR
      mutations were younger than those without mutations (60.6 versus 67.4 years,
      p=0.03). These results suggest that tumors with EGFR mutations may progress more
      rapidly and develop into invasive cancer faster than those without mutations.
      Alternatively it is also possible that some invasive adenocarcinomas with EGFR
      mutations may not follow the AAH-adenocarcinoma sequence. We analyzed 24 patients
      with multiple lung lesions and 13 patients had at least one lesion that had
      either an EGFR or K-ras mutation. In all cases each lesion had a different
      mutation status. This finding suggests that the genetic alterations responsible
      for the development of lung adenocarcinoma occur randomly even under exposure to
      the same carcinogen.

PMID- 15950316
TI  - A lack of prognostic significance regarding DeltaNp63 immunoreactivity in lung
      cancer.
AB  - DeltaNp63 is an isoform of the p53 homologue p63, which lacks an amino-terminal
      transactivation domain and antagonizes the induction of the gene expression by
      Deltap63. The aim of this study was to detect the DeltaNp63 expression in lung
      cancer using immunohistochemical (IHC) staining, and to evaluate the relationship
      between theDeltaNp63 expression level and the prognosis based on resected lung
      cancer tissues specimens from the of patients. We used immunohistochemistry to
      analyze the protein expression of DeltaNp63 in paraffin-embedded tumor samples
      from 161 well-characterized squamous cell carcinoma patients and compared the
      expression level of DeltaNp63, clinical variables and the survival outcome.
      Seventy-seven patients (47.8%) showed positive staining for DeltaNp63 in the
      nuclei of tumor cells. No significant difference was observed between the
      DeltaNp63 expression and the gender, age at operation, pathologic stage,
      pathologic T status, and pathologic N status. Based on the actuarial survival
      method, Kaplan-Meier method, and the log-rank test, the DeltaNp63 expression was
      not associated with survival for lung cancer. Differences in survival remained
      insignificant even after lung cancer patients were stratified according to stage
      or differentiation. The prognostic effects of DeltaNp63 expression do not appear
      to act as an important prognostic indicator in lung cancer. Our findings do not
      support that immunocytochemical markers demonstrate a relevant prognostic role in
      lung cancer.

PMID- 15950317
TI  - Food and land use. The influence of consumption patterns on the use of
      agricultural resources.
AB  - This paper assesses the relationship between food consumption patterns and the
      use of agricultural land. First, it calculates the amount of land needed to
      produce singular foods, and second, it assesses land requirements of food
      consumption patterns. The paper observes large differences among requirements for
      specific foods. Especially livestock products, fats, and coffee have large land
      requirements. The consumption of specific foods can change rapidly over time,
      causing shifts in land requirements. A rise or fall of requirements, however,
      depends on the initial consumption pattern. Patterns based on animal foods
      shifting towards market foods containing more staples require less land. This
      dietary change direction was shown for Dene/Metis communities in Canada. Patterns
      based on staples shifting toward diets containing more livestock foods and
      beverages require more land. This change direction was observed in the
      Netherlands. Per capita land requirements differ among countries. In Europe,
      Portugal showed the smallest requirement (1814m2), Denmark the largest (2479m2).
      The Danish pressure was mainly caused by large consumption of beer, coffee, fats,
      pork, and butter. The trend toward food consumption associated with affluent life
      styles will bring with it a need for more land. This causes competition with
      other claims, such as infrastructural developments or ecological forms of
      agriculture.

PMID- 15950318
TI  - Protein intake and body-weight regulation.
AB  - Body-weight management requires a multi-factorial approach. Recent findings
      suggest that an elevated protein intake seems to play such a key role in body
      weight management, through (i) increased satiety related to increased diet
      induced thermogenesis, (ii) its effect on thermogenesis, (iii) body composition,
      and (iv) decreased energy-efficiency. Supported by these mechanisms a relatively
      larger weight loss and stronger body-weight maintenance thereafter have been
      observed.

PMID- 15950319
TI  - Age-dependent changes of glyoxalase I expression in human brain.
AB  - Increased modification and crosslinking of proteins by advanced glycation end
      products (AGEs) is a characteristic feature of aging, and contributes to the
      formation of many of the lesions of neurodegenerative diseases including
      neurofibrillary tangles and amyloid plaques in Alzheimer's disease. Therefore,
      defense mechanisms against AGE formation or detoxification of their precursors
      such as the glyoxalase system are of particular interest in aging research. Thus,
      we investigated the age-dependent protein expression, the activity as well as the
      RNA level of glyoxalase I in Brodmann area 22 (auditory association area of
      superior temporal gyrus) of the human cerebral cortex. Our immunohistochemical
      results demonstrate the localization of glyoxalase I in neurons, predominantly
      pyramidal cells, as well as in astroglia, located predominantly in the subpial
      region. The number of glyoxalase I expressing neurons and astroglia increases
      with age, with a peak at approximately 55 years, and progressively decreases
      thereafter. These results were confirmed by biochemical investigations in total
      brain tissue, where the RNA, the protein level as well as the activity of
      glyoxalase I enzyme were analyzed in different age groups. In conclusion, the
      increase in glyoxalase I expression up to the age of 55 may be a compensatory
      mechanism against high oxoaldyde levels and the accumulation of AGEs. However,
      the decline of glyoxalase expression and activity in old age, possibly caused by
      impairment in transcription or/and translation, may subsequently lead to
      increased levels of reactive carbonyl compounds, followed by protein
      crosslinking, inflammation, oxidative stress and neuronal degeneration.

PMID- 15950320
TI  - The effects of antioxidants in the senescent auditory cortex.
AB  - We investigated whether a 2-month dietary supplementation of antioxidants, in the
      form of blueberry phytochemicals, could reverse or retard the age-related decline
      in temporal processing speed observed in the aged rat. To this end, extracellular
      single unit responses to frequency modulated (FM) sweeps were recorded in the
      primary auditory cortex (AI) of aged rats that had been placed on either a
      blueberry-supplemented or control diet 2 months prior to the physiological
      recordings. Results showed that most cells recorded from the blueberry-fed rats
      responded most vigorously to fast FM sweeps, similar to that observed in young
      rats. In contrast, the majority of cells recorded from the control rats showed a
      preference for slow FM sweep rates. These results suggest that age-related
      changes in temporal processing speed in A1 may be reversed by dietary
      supplementation of blueberry phytochemicals.

PMID- 15950321
TI  - Oxidative modification and down-regulation of Pin1 in Alzheimer's disease
      hippocampus: A redox proteomics analysis.
AB  - Alzheimer disease (AD) is characterized neuropathologically by intracellular
      neurofibrillary tangles (NFT) and of extracellular senile plaques (SP), the
      central core of which is amyloid beta-peptide (Abeta) derived from amyloid
      precursor protein (APP), a transmembrane protein. AD brain has been reported to
      be under oxidative stress that may play an important role in the pathogenesis and
      progression of AD. The present proteomics study is focused on identification of a
      specific target of protein oxidation in AD hippocampus that has relevance to the
      role of oxidative stress in AD. Here, we report that the protein, Pin1, is
      significantly down-regulated and oxidized in AD hippocampus. The identity of Pin1
      was confirmed immunochemically. Analysis of Pin1 activity in AD brain and
      separately as oxidized pure Pin1 demonstrated that oxidation of Pin1 led to loss
      of activity. Pin1 has been implicated in multiple aspects of cell cycle
      regulation and dephosphorylation of tau protein as well as in AD. The in vivo
      oxidative modification of Pin1 as found by proteomics in AD hippocampus in the
      present study suggests that oxidative modification may be related to the known
      loss of Pin1 isomerase activity that could be crucial in AD neurofibrillary
      pathology. Taken together, these results provide evidence supporting a direct
      link between oxidative damage to neuronal Pin1 and the pathobiology of AD.

PMID- 15950322
TI  - RET expression does not change with age in the substantia nigra pars compacta of
      rhesus monkeys.
AB  - Parkinson's disease is characterized by bradykinesia, rigidity and a resting
      tremor and the underlying basis for those symptoms is the loss of dopaminergic
      cells in the nigrostriatal system. Similar to PD, an age-related decrease
      locomotor activity and the expression of tyrosine hydroxylase immunoreactivity
      has been observed in rhesus monkeys, but the reason for this decrease in
      dopaminergic function remains to be elucidated. Trophic factors such as glial
      cell line derived neurotrophic factor (GDNF) and neurturin sustain the
      dopaminergic phenotype in midbrain neurons and act through a common receptor
      tyrosine kinase (RET). Examination of RET expression by immunohistochemistry was
      performed on sections of tissue containing the substantia nigra pars compacta of
      young, middle, and old aged rhesus monkeys. Stereological estimates of the number
      and cellular area of RET-immunoreactive cells found no change with age.
      Estimation of changes in RET protein using fluorescence intensity measurement was
      also similar across age groups. The results indicate that the mechanisms of GDNF
      and neurturin signaling remain intact with age, and therefore these trophic
      factors may be able to enhance the dopaminergic function of neurons in the
      nigrostriatal system, when administered to individuals of any age.

PMID- 15950323
TI  - Pathogenic accumulation of APP in fast twitch muscle of IBM patients and a
      transgenic model.
AB  - Inclusion body myositis (IBM) is the most common age-related degenerative
      skeletal muscle disorder. The aberrant intracellular accumulation of the beta
      amyloid (Abeta) peptide within skeletal muscle is a pathological hallmark of IBM.
      Skeletal muscle is comprised of both slow and fast twitch fibers, which are
      present in different proportions in various muscles. It remains unclear if fast
      and/or slow twitch fibers are differentially involved in IBM pathogenesis. To
      better understand the molecular pathogenesis of IBM, we analyzed human IBM muscle
      biopsies and muscle from a transgenic mouse model of IBM (MCK-betaAPP). Here we
      report that the majority of histopathologically-affected fibers in human IBM
      biopsies were type II fast fibers. Skeletal muscle from MCK-betaAPP mice
      exhibited higher transgene expression and steady-state levels of human betaAPP in
      fast type IIB fibers compared to slow type I fibers. These findings indicate that
      fast twitch fibers may selectively accumulate and be more vulnerable to betaAPP-
      and Abeta-mediated damage in IBM. These findings also highlight parallels between
      the MCK-betaAPP mice and the human IBM condition.

PMID- 15950324
TI  - Synthesis and properties of isocannabinoid and cholesterol derivatized
      rhamnosurfactants: application to liposomal targeting of keratinocytes and skin.
AB  - The usefulness of vesicles to cargo material depends on the design of new ligands
      able to incorporate easily inside the bilayer and also to direct the vesicles to
      the targeted site. Therefore, the synthesis of two new rhamnose-bearing
      surfactants is described. The hydrophobic part consists of cholesterol (in
      compound 3) and citrylidene phloroglucinol (in compound 6). The ability of these
      two rhamnolipids to incorporate into a DPPC membrane and to form aggregates is
      investigated, respectively, by differential scanning calorimetry and by surface
      tension measurements. Those two new surfactants were incorporated in fluorescent
      liposomes to study their interactions with keratinocytes and skin sections.
      Intraliposomal delivery to keratinocytes was observed in both cases, even if the
      kinetics of delivery were different according to the rhamnosurfactant used. Skin
      sections were stained by both liposomal formulations, and different interactions
      between the liposomes and skin cells according to the surfactant used were noted.

PMID- 15950325
TI  - Design, synthesis and in vitro and in vivo antitumor activities of novel beta
      carboline derivatives.
AB  - To further our SAR study on the chemistry and antitumor activity/neurotoxicity of
      beta-carboline alkaloids, several series of beta-carboline derivatives with
      various substituents were designed and synthesized from the starting material l
      tryptophan on the basis of harmine chemical structure. Cytotoxic activities of
      these compounds were investigated in vitro. The results showed that some beta
      carboline derivatives had significant cytotoxic activities against human tumor
      cell lines. Among all the synthesized beta-carboline derivatives, the compounds
      27, 28 and 32, having a benzyl substituent at both position-2 and 9,
      respectively, were found to be the most potent compounds with IC50 value lower
      than 50 microM against all human tumor cell lines examined. Acute toxicities and
      antitumor activities of the selected beta-carboline derivatives in mice were also
      evaluated. The results demonstrated that a benzyl substituent at position-2
      increased the antitumor activity as well as acute toxicity significantly. However
      an (ethoxycarbonyl)amino substituent at position-3 reduced the acute toxicity as
      well as antitumor activity remarkedly. These data suggested that (1) the
      antitumor potencies of beta-carboline derivatives were enhanced by the
      introduction of benzyl substituent into the position-2; (2) the acute toxicity of
      beta-carboline derivatives reduced dramatically by the introduction of an
      appropriate substituent into the position-3 and 9; (3) the beta-carboline
      structure might be an important basis for the design and synthesis of new
      antitumor drugs with significant antitumor activity and low toxicity.

PMID- 15950326
TI  - Synthesis and antiplatelet activity of thioaryloxyacids analogues of clofibric
      acid.
AB  - The thiophene-, benzothiazole- and pyridine-thioaryloxyacids analogues of
      clofibric acid were synthesized and their antiplatelet activity was screened.
      Some compounds exhibited antiaggregating properties. The platelet-related
      haemostasis was measured on a PFA-100 analyzer using bull blood.

PMID- 15950327
TI  - Evaluation of AD472, a live attenuated recombinant herpes simplex virus type 2
      vaccine in guinea pigs.
AB  - An attenuated recombinant herpes simplex virus type 2 (HSV-2), designated as
      AD472, was constructed by deleting both copies of the gamma(1)34.5 gene, UL55-56,
      UL43.5, and the US10-12 region from HSV-2 strain G. This virus was engineered to
      be a safe and effective live attenuated HSV-2 vaccine and was tested in the
      guinea pig model of genital herpes to evaluate its ability to protect from
      disease upon challenge with the wild type (wt) virus, HSV-2 (G). AD472
      administered intramuscularly did not prevent infection or virus replication in
      the vaginal tract, but did reduce both lesion development and severity in a dose
      dependent manner in guinea pigs challenged with the wt virus. Frequency of
      reactivation from latency was low compared with that of the parent virus, HSV-2
      (G). Immunization with AD472 at doses of 1x10(5)PFU generally precluded
      colonization of the ganglia or establishment of latency by the challenge virus.
      Results presented here support the concept of a rationally engineered live
      attenuated vaccine for the prevention of the genital disease associated with
      infection by HSV-2.

PMID- 15950328
TI  - Molecular and biological characterization of simian-human immunodeficiency virus
      like particles produced by recombinant fowlpox viruses.
AB  - Virus-like particles (VLPs) mimicking the simian-human immunodeficiency virus
      SHIV89.6P (VLPSHIV) were produced by co-infection of Vero cells with fowlpox
      SIVgag/pol (FPgag/polSIV) and fowlpox HIV-1env89.6P (FPenv89.6P) recombinant
      viruses. As a necessary prerequisite for a more efficient vaccine approach,
      ultrastructural, functional and molecular characterizations of VLP(SHIV) were
      performed in the SHIV-macaque model to verify the similarity of these particles
      to SHIV89.6P. Here we show that VLPSHIV can infect T cells by fusion without
      replication, as demonstrated by the absence of new viral progeny in VLPSHIV
      infected C8166 cells. Biochemical characterization showed identical protein
      profiles of VLPSHIV and SHIV89.6P, and ultrastructural analysis of Vero cells
      releasing VLPSHIV also confirmed the morphological similarity of these
      pseudovirions to SHIV89.6P particles. Viral mRNAs were also found packaged inside
      the core of VLPSHIV by RT-PCR and reverse transcriptase assays.

PMID- 15950329
TI  - The effectiveness of the mumps component of the MMR vaccine: a case control
      study.
AB  - In 1998/1999, an outbreak of mumps occurred among children of a religious
      community in North East London. A case control study was conducted to assess the
      effectiveness of the mumps component of the MMR vaccine. One hundred and sixty
      one cases of mumps were identified and 192 controls were selected. Fifty-one
      percent of cases and 77% of controls had a history at least one MMR vaccination.
      The observed effectiveness of any MMR vaccination adjusted for age, sex and
      general practice was 69% (95% CI: 41-84%). This is consistent with the results of
      other observational studies of mumps containing vaccines, but lower than the
      immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is
      because observational studies tend to underestimate vaccine effectiveness, and
      because immunogenicity is not necessarily an accurate biological marker of
      vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62
      96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination
      programme remains the best method for controlling mumps infection in the
      community.

PMID- 15950330
TI  - Optimisation of sampling for the temporal monitoring of technetium-99 in the
      Arctic marine environment.
AB  - Monitoring of the marine environment for radioactivity, for both radiological
      protection and oceanographic purposes, remains an expensive and labour intensive
      activity due to the large sample volumes needed and the complex and lengthy
      analytical procedures required to measure low levels of contamination. Because of
      this, some consideration must be given to the design of sampling plans to ensure
      effective and efficient sampling that can be defended on the basis of scientific
      rationale. This article tests the hypothesis that geostatistical techniques may
      prove of use in the optimisation and design of sampling regimes for the
      monitoring of temporal fluctuations in the levels of technetium at a location in
      the Norwegian Arctic marine environment. The level of temporal correlation
      exhibited by two relevant time series was investigated and the information used
      to observe the effect of sampling frequency on the production of monthly
      estimates of activity of technetium in both seawater and seaweed. The results
      indicate that reduced sampling frequency allows production of estimates that
      acceptably replicate the actual data and that use of geostatistical procedures
      may offer advantages in the planning of monitoring systems for marine
      radioactivity. The use of an oceanographic model was also investigated as a means
      of assessing the temporal correlation prior to actual sampling, an approach that
      may offer significant advantages by reducing the need to have lengthy time series
      prior to designing sampling regimes.

PMID- 15950331
TI  - Influence of rainfall characteristics on elimination of aerosols of cesium,
      strontium, barium and tellurium deposited on grassland.
AB  - This work is aimed at quantifying foliar transfer of cesium, strontium, barium
      and tellurium under the influence of rainfall characteristics (intensity,
      frequency and time elapsed between contamination and first rainfall). Grassland
      boxes were contaminated by dry deposition of multi-element aerosols of (137)Cs,
      (85)Sr, (133)Ba and (123m)Te. They were grown in a greenhouse under controlled
      conditions. The treatments consisted of mowing and applying rainfalls (8 and 30
      mmh(-1)) at different times after the contamination. At a leaf area index of
      5.9+/-1.9, interception of the aerosols was similar for the 4 radionuclides
      (83.8+/-5.9%). Dew produced significant radionuclide accumulation in the base of
      the vegetation and transfer to the soil. For moderate intensity, an early (2 days
      after contamination) first rainfall was as efficient, in terms of leaf wash-off,
      as a longer rainfall occurring later (6 days after contamination). For early
      rainfalls, eliminated activities were comparable because the influence of rain
      intensity was compensated by rain duration. However, for late rainfalls, wash-off
      efficiency increased with rainfall intensity. Total transfer factors (TTF) were
      determined on whole grass immediately after 4 rainfalls and at harvest. After 4
      medium intensity rainfalls, rain frequency did not influence total transfer
      factors (TTF) of strontium, barium and tellurium (about 0.2, 0.3 and 0.35 Bq
      kg(fresh weight)(-1) by Bq m(-2), respectively). Cesium TTF value was lower in
      the case of a weekly rain (0.1 against 0.2 Bq kg(fresh weight)(-1) by Bqm(-2)).
      TTF values were similar for twice-a-week rainfalls, whatever their intensity.
      They were higher for weekly rains of high intensity (between 0.3 and 0.75 Bq
      kg(fresh weight)(-1) by Bqm(-2) against 0.1-0.35 Bq kg(fresh weight)(-1) by Bq m(
      2), depending on the radionuclides). TTF values attested that wash-off was more
      efficient when rainfalls lasted longer. Field loss on the top of the leaves was
      well described by an offset exponential model. The half-lives varied with
      rainfall characteristics from 4 days for cesium, strontium and barium to 20 days
      for tellurium. The offset value varied between 0% for tellurium (high intensity
      rainfalls) and 14% for cesium (medium intensity rainfalls).

PMID- 15950332
TI  - Determination of 129I/127I in aerosol samples in Seville (Spain).
AB  - In this work we present results of the (129)I/(127)I ratio in aerosols of
      Seville, Southwest of Spain (37.4 degrees N,6 degrees W). A radiochemical method
      is applied to extract the iodine from the aerosols and prepare samples to be
      measured by accelerator mass spectrometry (AMS) at the ETH facility in Zurich. We
      have found the possibility of monitoring the (129)I/(127)I isotopic ratio on a
      two-days basis with sensitivities in the order of 10(4)-10(5) atoms (129)I/m(3),
      and values of 10(-8)-10(-9) for the isotopic ratio.

PMID- 15950333
TI  - An operative lagrangian model for simulating radioactivity dispersion in the
      Strait of Gibraltar.
AB  - GISPART (GIbraltar Strait PARticle Tracking model) is a three-dimensional
      particle tracking code to simulate the dispersion of radionuclides in the Strait
      of Gibraltar. It consists of a hydrodynamic module that is run off-line to
      determine tidal constants and residuals in the domain. This information is stored
      in several files that are read by the dispersion module to reconstruct water
      movements. The dispersion module uses a lagrangian approach. Thus, a radionuclide
      release is simulated by a number of particles, whose paths are computed
      individually. Radionuclide concentrations are obtained from the density of
      particles per water volume unit. Some examples of results are shown. The model is
      also available on-line.

PMID- 15950334
TI  - Endoscopically assisted operative retrieval of parotid stones.
AB  - The treatment of large parotid stones remains a problem. We describe a technique
      in which microendoscopy is used to locate the stone and facilitate its removal.
      Over a 12-month period, eight patients were treated and seven stones removed
      successfully. The remaining duct was obstructed by a stricture. In six instances,
      the parotid duct was repaired and in two ligated. The mean follow up was 10
      months (range 6-18) and there have been no complications. Our initial experience
      suggests that microendoscopy to locate the stone and facilitate its removal is an
      option in the management of persistent parotid stones.

PMID- 15950335
TI  - Herpes zoster in the ulnar nerve distribution.
AB  - Varicella zoster is a ubiquitous virus which usually affects school-aged children
      as Chicken Pox. While the initial disease is self-limiting and seldom severe, the
      virus remains in the body. It lies dormant in the dorsal root ganglia and
      reactivation may occur years later with variable presentations as Herpes Zoster,
      or Shingles. While Shingles is common, it rarely presents exclusively in the
      upper extremity. It is important that hand surgeons recognize the possibility of
      zoster infection, with or without a rash, when evaluating the onset of neuralgia
      in a dermatomal distribution in the upper limb. Early diagnosis allows rapid and
      appropriate treatment, with a lower risk of complications. We report on a case of
      Herpes Zoster isolated to the ulnar nerve distribution in a young woman.

PMID- 15950336
TI  - Multiple plexiform schwannoma of the hand and forearm: a long-term follow-up.
AB  - We present a case report to illustrate the differential diagnosis and management
      of a multiple plexiform schwannoma involving the main nerve trunks of the upper
      limb in a 4 year-old boy. The tumour was diagnosed by MRI scan and histological
      examination. A 12 year follow-up is presented in which, despite multiple
      recurrences, the condition has been controlled by surgical means and the limb
      salvaged.

PMID- 15950337
TI  - Thumb polydactyly with symphalangism.
AB  - Three cases of thumb polydactyly in which one of the components demonstrated
      symphalangism are reported. This is a very rare anomaly and only one similar case
      could be found in the literature. The rarity of this anomaly was explained by the
      occurrence of two different abnormal molecular events along two different limb
      growth axes. Finally, the anomaly does not fit into the classification systems
      described for thumb polydactyly.

PMID- 15950338
TI  - The safest location for steroid injection in the treatment of carpal tunnel
      syndrome.
AB  - Steroid injections are routinely performed for carpal tunnel syndrome. Direct
      needle injury of the median nerve is the major complication of these injections.
      The safest location of the injection remains controversial. The purpose of this
      study is to define safe guidelines to avoid nerve injury. The distances between
      the Median nerve, Palmaris Longus, Flexor Carpi Ulnaris and Flexor Carpi Radialis
      tendons were measured pre-operatively, 1cm proximal to the distal wrist crease in
      93 endoscopic carpal tunnel releases. We found that the median nerve extended
      ulnarly beyond the Palmaris Longus tendon in 82 hands (88%). It is concluded that
      the median nerve is at risk if the injection is performed within 1cm on either
      the ulnar or radial side of the Palmaris Longus tendon. More ulnarly, there is
      risk to the ulnar pedicle. The safest location is to inject through the FCR
      tendon.

PMID- 15950339
TI  - Treatment of scaphoid non-union with a percutaneous corticocancellous bone graft.
AB  - Thirty-three symptomatic scaphoid non-unions were treated by a simple, minimally
      invasive procedure using a percutaneous autologous corticocancellous bone graft.
      After an average follow-up of 3.5 years, union was observed in 29 cases. These
      patients had no, or mild, pain at work and an almost normal range of motion and
      grip strength. No progression to osteoarthritis was observed.

PMID- 15950340
TI  - Effects of increased deposition of atmospheric nitrogen on an upland moor:
      nitrogen budgets and nutrient accumulation.
AB  - This study was designed to investigate the effect of long-term (11 years)
      ammonium nitrate additions on standing mass, nutrient content (% and kg ha(-1)),
      and the proportion of the added N retained within the different compartments of
      the system. The results showed that more than 90% of all N in the system was
      found in the soil, particularly in the organic (Oh) horizon. Added N increased
      the standing mass of vegetation and litter and the N content (kg N ha(-1)) of
      almost all measured plant, litter and soil compartments. Green tissue P and K
      content (kg ha(-1)) were increased, and N:P ratios were increased to levels
      indicative of P limitation. At the lowest treatment, most of the additional N was
      found in plant/litter compartments, but at higher treatments, there were steep
      increases in the amount of additional N in the underlying organic and mineral
      (Eag) horizons. The budget revealed that the proportion of added N found in the
      system as a whole increased from 60%, 80% and up to 90% in response to the 40, 80
      and 120 kg N ha(-1) year(-1) treatments, respectively.

PMID- 15950341
TI  - Fish community responses to metal pollution.
AB  - The effect of metal pollution on fish communities was assessed at 47 sites,
      including a Cd and Zn gradient. Fish community structure was assessed by applying
      diversity indices, index of biotic integrity and the abundance/biomass comparison
      method (ABC-index). To relate the community responses to metal pollution, toxic
      unit values for dissolved metals (TU(w)) and for metals in fish liver (TU(t))
      were calculated. If all sites were considered only a good relationship was found
      between the IBI and the TU(w), with 56% of the variation in IBI being described.
      Within the pollution gradient (sites 1--12) the described variation increased up
      to 85%. Relating the community structure to TU(t), the described variation in IBI
      further increased to 87%. Our results indicate that besides water quality other
      factors influenced diversity and ABC-index. The IBI proved a suitable index for
      the assessment of metal pollution, provided that other water quality
      characteristics meet the water quality criteria.

PMID- 15950342
TI  - Behavior and source characteristic of PCBS in urban ambient air of Yokohama,
      Japan.
AB  - To understand the behavior and sources of polychlorinated biphenyls (PCBs) in
      ambient air, gaseous and particulate phase concentrations were measured at
      Yokohama City, Japan, during March 2002 and February 2003. The concentration of
      total PCB and TEQ ranged from 62 to 250 pg/m(3) and from 2 to 14 fgTEQ/m(3),
      respectively. The gas-particle partition coefficient (K(p)) was obtained as a
      function of temperature. The relationship between the partition coefficient and
      the sub-cooled liquid vapor pressure (P(L)) was also established (coefficients of
      determination for log K(p) versus log P(L) plot were >0.76, except for three
      samples). As a result, the partition ratio of gaseous and particulate phase PCBs
      can be estimated for an arbitrary temperature. Principal component analysis (PCA)
      was applied to the source identification of PCBs in ambient air. The
      concentrations of 122 congeners between tetra-CBs and deca-CB were used as input
      variables, and three PCs with eigenvalue more than 10 were obtained. The
      principal component 1 (PC 1) accounted for 43.4% of the total variance, and was
      interpreted as volatilization from PCB products and/or sites polluted by PCBs.
      The concentrations of PCB congeners were strongly related with PC 1 which showed
      high correlation with temperature. PC 2 accounted for 22.3%, and was interpreted
      as PCBs from incineration sources, while PC 3 accounted for 10.8%, but could not
      be interpreted.

PMID- 15950343
TI  - Leaching of glyphosate and AMPA under two soil management practices in Burgundy
      vineyards (Vosne-Romanee, 21-France).
AB  - Some drinking water reservoirs under the vineyards of Burgundy are contaminated
      with herbicides. Thus the effectiveness of alternative soil management practices,
      such as grass cover, for reducing the leaching of glyphosate and its metabolite,
      AMPA, through soils was studied. The leaching of both molecules was studied in
      structured soil columns under outdoor conditions for 1 year. The soil was managed
      under two vineyard soil practices: a chemically treated bare calcosol, and a
      vegetated calcosol. After 680 mm of rainfall, the vegetated calcosol leachates
      contained lower amounts of glyphosate and AMPA (0.02% and 0.03%, respectively)
      than the bare calcosol leachates (0.06% and 0.15%, respectively). No glyphosate
      and only low amounts of AMPA (<0.01%) were extracted from the soil. Glyphosate,
      and to a greater extent, AMPA, leach through the soils; thus, both molecules may
      be potential contaminants of groundwater. However, the alternative soil
      management practice of grass cover could reduce groundwater contamination by the
      pesticide.

PMID- 15950344
TI  - An inter-laboratory study to test the ability of amendments to reduce the
      availability of Cd, Pb, and Zn in situ.
AB  - An international inter-laboratory research program investigated the effectiveness
      of in situ remediation of soils contaminated by cadmium, lead and zinc, measuring
      changes in soil and soil solution chemistry, plants and soil microbiota. A common
      soil, from mine wastes in Jasper County MO, was used. The soil was pH 5.9, had
      low organic matter (1.2 g kg(-1) C) and total Cd, Pb, and Zn concentrations of
      92, 5022, and 18 532 mg kg(-1), respectively. Amendments included lime,
      phosphorus (P), red mud (RM), cyclonic ashes (CA), biosolids (BIO), and water
      treatment residuals (WTR). Both soil solution and NH4NO3 extractable metals were
      decreased by all treatments. Phytotoxicity of metals was reduced, with plants
      grown in P treatments having the highest yields and lowest metal concentration
      (0.5, 7.2 and 406 mg kg(-1) Cd, Pb, and Zn). Response of soil micro-organisms was
      similar to plant responses. Phosphorus addition reduced the physiologically based
      extraction test Pb from 84% of total Pb extracted in the untreated soil to 34.1%.

PMID- 15950345
TI  - Historical perspective and future directions in Cognitive Behavioral Therapy for
      insomnia and behavioral sleep medicine.

PMID- 15950346
TI  - EPA's new guidance for assessing cancer risks from early life exposures:
      genotoxic mode of action and implications for human health-based standards.

PMID- 15950347
TI  - Priority setting in hospitals: fairness, inclusiveness, and the problem of
      institutional power differences.
AB  - Priority setting tends to take place in health care settings that are
      hierarchical and politically complex. Fair processes, as defined for example by
      Daniels' and Sabin's accountability for reasonableness framework, have been
      identified as essential for securing socially acceptable priority setting
      decisions. However, power differences in the decision-making context can pose a
      serious impediment to fair priority setting in health care organizations.
      Comparatively little attention has been paid to examining the institutional
      conditions within which priority setting decisions are made. We review a case
      study of priority setting in hospital operational planning in Toronto, which had
      been designed by executive leaders to be broadly inclusive of senior and middle
      level clinical and administrative leaders. We report three power differences that
      arose as limiting factors on the inclusiveness of the priority setting process.
      We argue that these findings have significant theoretical implications for the
      accountability for reasonableness framework and propose a fifth condition, the
      "empowerment condition", which states that there should be efforts to minimise
      power differences in the decision-making context and to optimise effective
      opportunities for participation in priority setting.

PMID- 15950348
TI  - Health status among young people in Slovakia: comparisons on the basis of age,
      gender and education.
AB  - This study examines the health status of young people in Slovakia. Six subjective
      health indicators (self-rated health, long-standing illness, vitality, mental
      health, long-term well-being over the last year and occurrence of health
      complaints during the previous month) were used to assess the health status of
      three age groups: first grade secondary school students (mean age 15.9 years),
      third grade students (mean age 17.8 years) and secondary school leavers (mean age
      19.6 years). Females rated their health worse than males on all six indicators
      (most of these differences were statistically significant). For males, younger
      age was associated with better self-rated health, less long-standing illness and
      higher levels of long-term well-being during the previous year. For females, the
      age differences were more complicated: third grade females reported significantly
      worse health status in terms of vitality, long-standing illness and number of
      health complaints than the other two age groups. An analysis of health status by
      educational level (attendance at or completion of grammar, technical or
      apprentice school), revealed that grammar school third grade females reported
      worse health than all other respondents on all six indicators. The third grade of
      grammar school in Slovakia puts particular stresses on students and, since it has
      been suggested that females may react more negatively than males to stressful
      events, this may contribute to their more negative self reports.

PMID- 15950349
TI  - The combined dexamethasone/CRH test as a potential surrogate marker in
      depression.
AB  - There is compelling evidence that impaired corticosteroid receptor function is
      the key mechanism in the pathogenesis of depression resulting in a dysfunctional
      stress hormone regulation, which can be most sensitively detected with the
      combined dexamethasone (dex)/corticotropin releasing hormone (CRH) test.
      Treatment with different kinds of antidepressants is associated with a reduction
      of the hormonal responses to the combined dex/CRH test suggesting normalization
      of impaired corticosteroid receptor signaling as the final common pathway of
      these drugs. Consequently, the combined dex/CRH test is suggested as a screening
      tool to decide whether new compounds designed as antidepressants provide
      sufficient efficacy to normalize corticoid receptor signaling in depressed
      patients. We summarize own data and findings from the literature suggesting that
      (1) the neuroendocrine response to the combined dex/CRH test is elevated during a
      major depressive episode, but (2) tends to normalize after successful treatment.
      (3) Favorable response to antidepressant treatment can be predicted by
      determining the dex suppresser status on admission. For optimal prediction of non
      response to antidepressant treatment, however, the results of a second dex/CRH
      test are necessary. These findings, together with the fact that impaired
      corticosteroid receptor signaling is considered as key mechanism of the
      pathogenesis in depression, support the suitability of the combined dex/CHR test
      as a surrogate marker for treatment response in depression. In conclusion, the
      combined dex/CRH test is a promising candidate to serve as a screening tool for
      the antidepressive effects of new compounds in clinical drug trials. Furthermore,
      the test appears to be capable of predicting the individual likelihood to respond
      to a current antidepressant treatment. If a drug treatment fails to normalize the
      outcome of the combined dex/CRH test, a change of the treatment strategy is
      recommended. Further systematic research is required and already ongoing to
      confirm the suitability of the combined dex/CRH test as a surrogate marker in
      depression.

PMID- 15950350
TI  - Olanzapine-induced leucopenia and neutropenia.
AB  - Atypical antipsychotics, including olanzapine, were originally expected to reduce
      the risk of haematological toxicity and to be safe alternatives to clozapine. We
      report a case of patient who developed leucopenia and neutropenia during
      treatment with olanzapine.

PMID- 15950351
TI  - Safety and effectiveness of olanzapine in monotherapy: a multivariate analysis of
      a naturalistic study.
AB  - BACKGROUND: This study investigated safety and effectiveness of olanzapine in
      monotherapy compared with conventional antipsychotics in treatment of acute
      inpatients with schizophrenia. METHOD: This was a prospective, comparative,
      nonrandomized, open-label, multisite, observational study of Spanish inpatients
      with an acute episode of schizophrenia. Data included safety assessments with an
      extrapyramidal symptoms (EPS) questionnaire and the report of spontaneous adverse
      events, plus clinical assessments with the Brief Psychiatric Rating Scale (BPRS)
      and the Clinical Global Impressions-Severity of Illness (CGI-S). A multivariate
      methodology was used to more adequately determine which factors can influence
      safety and effectiveness of olanzapine in monotherapy. RESULTS: 339 patients
      treated with olanzapine in monotherapy (OGm) and 385 patients treated with
      conventional antipsychotics (CG) were included in the analysis. Treatment
      emergent EPS were significantly higher in the CG (p<0.0001). Response rate was
      significantly higher in the OGm (p=0.005). Logistic regression analyses revealed
      that the only variable significantly correlated with treatment-emergent EPS and
      clinical response was treatment strategy, with patients in OGm having 1.5 times
      the probability of obtaining a clinical response and patients in CG having 5
      times the risk of developing EPS. CONCLUSION: In this naturalistic study
      olanzapine in monotherapy was better-tolerated and at least as effective as
      conventional antipsychotics.

PMID- 15950353
TI  - A subchronic toxicity study in rats and genotoxicity tests with an aqueous
      ethylcellulose dispersion.
AB  - Surelease Aqueous Ethylcellulose Dispersion is an excipient used as a modified
      release coating for beads, granules, non-pariels, drug crystals and tablets and
      for taste masking applications for drug products and dietary supplement products.
      A study was conducted to assess the toxicity of spray-dried Surelease when
      administered orally, via dietary admixture, to Sprague-Dawley CD rats
      (20/sex/group) at dose levels of 0, 2000, 3500, and 5000 mg/kg/day for a period
      of at least 3 months. After 3 months of treatment, all rats scheduled for
      terminal sacrifice were killed and selected organs were weighed. Complete
      macroscopic examinations and histopathological evaluation of selected tissues
      were conducted on all animals. Neuropathological evaluations were performed on 5
      animals/sex/group. No mortality occurred during the study. Clinical observations,
      ophthalmology, body weight and food consumption, hematology, coagulation,
      clinical chemistry, urinalysis, functional observational assessments, motor
      activity, organ weights and ratios and macroscopic and microscopic observations
      did not reveal any significant, consistent, dose-dependent test article-related
      adverse effects. The NOAEL (no-observed-adverse-effect-level) is 5000 mg/kg/day,
      the highest dose tested. A series of genotoxicity tests were conducted with
      Surelease. Surelease showed no evidence of mutagenic activity in the bacterial
      reverse mutation test with and without metabolic activation and in the in vitro
      cell mutation assay under the experimental conditions employed. Surelease did not
      show any evidence of causing chromosome damage or bone marrow cell toxicity when
      administered by gavage in the mouse micronucleus in vivo test procedure. These
      findings support the safety of Surelease for use as an excipient.

PMID- 15950352
TI  - Pharmacogenetics in model systems: defining a common mechanism of action for mood
      stabilisers.
AB  - Defining the underlying causes of psychiatric disorders has provided an ongoing
      and intractable problem. The analysis of the genetic basis of manic depression,
      in particular, has been impeded by the absence of a suitable model system and by
      the lack of candidate causative genes. One recent approach to overcome these
      problems has involved identifying those genes which control the sensitivity to
      anti-manic drugs in a model organism. Characterisation of the role of these genes
      and their encoded proteins in this model has allowed the analysis of their
      mammalian homologues to elucidate the therapeutic role of these drugs and the
      possible aetiology of manic depression. This approach has been used successfully
      with the cellular slime mould, Dictyostelium discoideum. This article introduces
      the use of model systems for pharmacogenetics research. It describes the
      identification of prolyl oligopeptidase in D. discoideum as a modulator of
      inositol phosphate signalling, and the subsequent identification of a common
      mechanism of action of three anti-manic drugs in mammalian neurons. The use of
      pharmacogenetics in model systems will provide a powerful tool for the ongoing
      analysis of both the treatment and cause of psychiatric disorders.

PMID- 15950354
TI  - Food safety: a guide to Internet resources.
AB  - This report provides a brief overview of several reliable Internet resources
      concerning food toxicology. Some helpful Internet resources have been identified
      on the basis of quality criteria, of their relevance and the languages
      availability. The report includes four topic areas, the first provides a brief
      description of international resources, the second focuses on European resources,
      the third provides a description of some national resources and the last is a
      short overview of some databanks available on web.

PMID- 15950355
TI  - Cisplatin-mediated DNA double-strand breaks in replicating but not in quiescent
      cells of the yeast Saccharomyces cerevisiae.
AB  - DNA double-strand breaks (DSBs) are formed during the processing of DNA
      interstrand crosslinks in replicating yeast and Chinese hamster cells exposed to
      DNA crosslinkers such as psoralen plus UVA or nitrogen mustard. They were also
      detected in human cells after treatment with photoactivated psoralen or mitomycin
      C. In contrast, no DSBs were observed after exposure of Chinese hamster cells to
      cisplatin, another crosslinking agent widely used for the therapy of various
      cancers, challenging a common role for DSBs in the processing of DNA interstrand
      crosslinks. Here we report for the first time that cisplatin-mediated DSBs are
      induced in replicating but not quiescent cells of the yeast Saccharomyces
      cerevisiae. When the main pathway of repair of DSBs is inhibited, these breaks
      accumulate in replicating cells. Thus it appears that DNA interstrand crosslinks
      induced by different crosslinking agents, including cisplatin, are processed
      yielding DSBs as an intermediate lesion. In stationary cells, however, removal of
      DNA interstrand crosslinks after cisplatin treatment occurs without the formation
      of DSBs. These findings point to an altered mode of processing of cisplatin-DNA
      adducts in replicating versus quiescent cells.

PMID- 15950356
TI  - An European inter-laboratory validation of alternative endpoints of the murine
      local lymph node assay: first round.
AB  - The new OECD guideline 429 (skin sensitization: local lymph node assay) is based
      upon a protocol, which utilises the incorporation of radioactivity into DNA as a
      measure for cell proliferation in vivo. The guideline also enables the use of
      alternative endpoints in order to assess draining lymph node (LN) cell
      proliferation. Here we describe the first round of an inter-laboratory validation
      of alternative endpoints in the LLNA conducted in seven laboratories. The
      validation study was managed and supervised by the Swiss Agency for Therapeutic
      Products, Swissmedic. Statistical analyses of all data were performed by an
      independent centre at the University of Bern, Department of Statistics. Ear
      draining, LN weight and cell count were used to assess proliferation instead of
      radioactive labeling of lymph node cells. In addition, the acute inflammatory
      skin reaction was measured by ear swelling and weight of circular biopsies of the
      ears to identify skin irritating properties of the test items.
      Hexylcinnamaldehyde (HCA) and three blinded test items were applied to female, 8-
      10 weeks old NMRI and BALB/c mice. Results were sent via the independent study
      coordinator to the statistician. The results of this first round showed that the
      alternative endpoints of the LLNA are sensitive and robust parameters. The use of
      ear weights added an important parameter assessing the skin irritation potential,
      which supports the differentiation of pure irritative from contact allergenic
      potential. There were absolute no discrepancies between the categorisation of the
      three test substances A--C determined by each single participating laboratories.
      The results highlighted also that many parameters do have an impact on the
      strength of the responses. Therefore, such parameters have to be taken into
      consideration for the categorisation of compounds due to their relative
      sensitizing potencies.

PMID- 15950357
TI  - Efficacy of bystander CPR: intervention by lay people and by health care
      professionals.
AB  - BACKGROUND: Early cardiopulmonary resuscitation (CPR) by bystanders prior to the
      arrival of the rescue team has been shown to be associated with increased
      survival after out-of-hospital cardiac arrest. The aim of this survey was to
      evaluate the impact on survival of no bystander CPR, lay bystander CPR and
      professional bystander CPR. METHODS: Patients suffering an out-of-hospital
      cardiac arrest in Sweden between 1990 and 2002 who were given CPR and were not
      witnessed by the ambulance crew were included. RESULTS: In all, 29,711 patients
      were included, 36% of whom received bystander CPR prior to the arrival of the
      rescue team. Among the latter, 72% received CPR from lay people and 28% from
      professionals. Survival to 1 month was 2.2% among those who received no bystander
      CPR, 4.9% among those who received bystander CPR from lay people (p<0.0001) and
      9.2% among those who received bystander CPR from professionals (p<0.0001 compared
      with bystander CPR by lay people). In a multivariate analysis, lay bystander CPR
      was associated with improved survival compared to no bystander CPR (OR: 2.04; 95%
      CI: 1.72-2.42), and professional bystander CPR was associated with improved
      survival compared to lay bystander CPR (OR: 1.37; 95% CI: 1.12-1.67). CONCLUSION:
      Among patients suffering an out-of-hospital cardiac arrest, bystander CPR by lay
      persons (excluding health care professionals) is associated with an increased
      chance of survival. Furthermore, there is a distinction between lay persons and
      health care providers; survival is higher when the latter perform bystander CPR.
      However, these results may not be explained by differences in the quality of CPR.

PMID- 15950358
TI  - Spinal cord injury (SCI)--prehospital management.
AB  - Up to 20,000 patients annually suffer from spinal cord injury (SCI) and 20% of
      these die before being admitted to the hospital in the United States as well as
      in the European Union. Prehospital management of SCI is of critical importance
      since 25% of SCI damage may occur or be aggravated after the initial event.
      Prehospital management includes examination of the patient, spinal
      immobilisation, careful airway management (intubation, if indicated, using manual
      in-line stabilisation), and cardiovascular support (maintenance of mean arterial
      blood pressure above 90 mm Hg) and blood glucose levels within the normal range.
      It is still not known whether additional specific therapy is useful. Studies have
      not demonstrated convincingly that methylprednisolone (MPS) or other
      pharmacological agents really have clinically significant and important benefits
      for patients suffering from SCI. Recently published statements from the United
      States also do not support the therapeutic use of MPS in patients suffering from
      SCI in the prehospital setting any more. Moreover, at this stage, it is not known
      whether therapeutic hypothermia or any further pharmacological intervention has
      beneficial effects or not. Therefore, networks for clinical studies in SCI
      patients should be established, as a basic requirement for further improvement in
      outcome in such patients.

PMID- 15950359
TI  - Excessive methaemoglobinaemia and multi-organ failure following 4-DMAP antidote
      therapy.
AB  - This report describes the clinical history of a patient intoxicated with methyl
      isocyanate (MIC), a toxic agent first receiving attention in 1984 after a mass
      accident in a pesticide plant in Bhopal, India, and treated with the cyanide
      specific antidote 4-DMAP. The numerous clinical conditions requiring 39-day
      intensive care treatment included ARDS, renal and hepatic failure, haemolysis,
      bone marrow depression, septic encephalopathy and critical illness
      polyneuropathy. The most outstanding condition, however, was a methaemoglobinemia
      of 86.7%, which was predominantly related to the use of 4-DMAP, although uptake
      of MIC may have been a significant contributing factor. Since significant cyanide
      intoxication could be excluded clinically and by laboratory testing in the
      initial phase of emergency treatment, most of the clinical effects were due to
      the side-effects of the antidote therapy. Due to intensive therapy, the patient
      survived without any neurological or organ deficit. This case shows that
      antidotes should be used cautiously in cases where uncertainties about the nature
      of the underlying toxic agent exist. This may prevent severe side-effects
      associated with antidote therapy, e.g. 4-DMAP, if there is-as in our case-a
      mismatch between the toxic agent and the antidote.

PMID- 15950360
TI  - Body mass index in endometriosis.
AB  - OBJECTIVE: Previous studies did not establish a clear correlation between the
      presence of endometriosis and the values of body mass index (BMI). STUDY DESIGN:
      The BMI of 366 women with endometriosis was compared to that of 248 controls
      undergoing laparoscopy because of benign gynaecological conditions. Significant
      differences at univariate analyses were confirmed by using Analysis of covariance
      (ANCOVA) to control for potential confounding variables. RESULTS: BMI was
      significantly lower in women with endometriosis than in controls (p < 0.001);
      this difference was confirmed when the analysis was restricted to subjects with
      normal BMI (18.50-24.99 kg/m(2)) (p = 0.002). 4.8% of control subjects and no
      woman with endometriosis were obese. No significant difference was observed in
      the BMI of women with mild (revised classification of the American Fertility
      Society, rAFS I-II) and severe endometriosis (rAFS III-IV). CONCLUSION: Women
      with endometriosis have lower BMI and are less frequently obese than control
      subjects. Further studies should investigate the physiopathological basis of
      decreased BMI in women with endometriosis.

PMID- 15950361
TI  - Severe perineal lacerations in nulliparous women and episiotomy type.
AB  - OBJECTIVE: To determine the patient-related factors associated with severe
      perineal lacerations in nulliparous women and to evaluate the effect of
      episiotomy type on the risk of severe perineal tears. STUDY DESIGN: In all, 400
      nulliparous women admitted in labor between June and December 2001 were
      prospectively enrolled. Maternal height, perineal length, fetal birth weight,
      fetal head circumference, and severe perineal lacerations (third and fourth
      degrees) were recorded. RESULTS: The rate of severe perineal lacerations was 2%
      (8/400); 3% with midline, 1% with mediolateral groups. In patients with severe
      lacerations, perineal length was significantly (p < 0.001) shorter and the head
      circumference of their babies in the midline significantly (p < 0.05) greater
      than normal, and birth weights were also significantly (p < 0.05) greater in the
      mediolateral group. A cut-off value for perineal length of 3.05 cm was found for
      severe lacerations in the midline group. CONCLUSION: If episiotomy is to be
      performed, it must be borne in mind that patients with a perineal length of < or
      = 3 cm have an elevated risk of severe perineal lacerations, and if clinical or
      ultrasound examination suggests that the fetal head is large, mediolateral
      episiotomy may be preferred. Otherwise, midline episiotomy must be considered.

PMID- 15950362
TI  - Repair of prolapse with vaginal sacrocolporectopexy: technique and results.
AB  - OBJECTIVE: Axis and support of the vagina can be restored by sacrocolporectopexy
      with preservation of coital function. We developed a new technique of
      transvaginal sacrocolporectopexy for patients with prolapse of uterus and vagina
      or prolapse of the vaginal vault. STUDY DESIGN: During a 4-year period, 20
      patients with vaginal vault prolapse and 83 patients with uterine and vaginal
      prolapse underwent transvaginal sacrocolporectopexy. Intra- and postoperative
      complications were recorded. After a mean follow-up period of 24 months (6-48),
      the result of surgery with respect to prolapse, incontinence, and sexuality was
      evaluated by patient interviews. RESULTS: No serious perioperative complications
      occurred with the exception of one patient with bleeding from a presacral vein.
      Subjectively, 84 patients (82%) were cured of prolapse symptoms. One patient had
      recurrent grade II vault prolapse and four patients developed a grade II
      rectocele. Five patients developed urge incontinence grade I. One patient
      developed fecal incontinence. No patient had coital problems as a sequelae of
      sacrocolporectopexy. CONCLUSION: Transvaginal sacrocolporectopexy is a safe
      procedure with a success rate comparable to sacrospinous fixation.

PMID- 15950363
TI  - Risk of venous thromboembolic disease in women A qualitative systematic review.
AB  - OBJECTIVES: To review the scientific evidence on the risk and prevention of
      venous thromboembolic disease (VTD) associated with specific clinical factors in
      women. STUDY DESIGN: Qualitative systematic review. DATA SOURCE: MEDLINE,
      Cochrane library, clinical practice guidelines, and referenced articles from
      these sources. RESULTS: Gender is not an independent risk factor of VTD. Absolute
      risks associated with each circumstance (per 1000 women-year) were: pregnancy,
      1.23; puerperium, 3.2; pregnancy in thrombophilic, 40; pregnancy and background
      of previous VTD, 110; use of third generation contraceptives, 0.3; postcoital
      pill, no risk; hormone replacement therapy, 0.2-5.9; tamoxifen, 3.6-12; and
      raloxifene, 9.5. The quality of the evidence on risk was classified as good or
      excellent. Evidence on prevention was scarce. Screening for thrombophilia prior
      to the prescription of contraceptives is not cost-effective as a strategy for
      prophylaxis. Use of low molecular weight heparin (LMWH) in high-risk pregnancies
      is supported by medium quality studies. CONCLUSIONS: There is good quality
      evidence on the magnitude of VTD risk associated with specific clinical factors
      in women. No studies on the utility of preventive measures have been performed
      for most of these circumstances. There is no evidence about the risk associated
      with the combination of several risk factors.

PMID- 15950364
TI  - Effectiveness of antiadhesion barriers in preventing adhesion after myomectomy in
      patients with uterine leiomyoma.
AB  - BACKGROUND: Myomectomy often causes adhesion formation and decreases subsequent
      fertility. The purpose of the present study was to evaluate the effectiveness of
      several antiadhesion barrier materials in preventing adhesion after myomectomy.
      METHODS: We prospectively classified 63 women undergoing myomectomy alone into
      four groups according to the type of antiadhesion material used: Hyaluronic acid
      carboxymethylcellulose film (Seprafilm) (n = 21, Group 1), Dextran 40 (10%
      Dextran 40 Low Injection) (n = 17, Group 2), factor 13 with fibrinogen
      (Beriplast) (n = 12, Group 3) and control (n = 13, Group 4). We performed early
      second-look laparoscopy after the seventh post-operative day in all patients and
      examined adhesion formation in the abdominal cavity. The incidence of adnexal
      adhesions was evaluated according to the American Fertility Association (AFS)
      adhesion score. RESULTS: The incidence of uterine adhesion was 14.3% in Group 1,
      70.6% in Group 2, 75.0% in Group 3 and 76.9% in Group 4. Adhesion formation in
      Group 1 was significantly less than that in Group 2 (p = 0.0004), Group 3 (p =
      0.0005) and Group 4 (p = 0.0003). The incidence of peritoneal adhesion was 14.3%
      in Group 1, 29.4% in Group 2, 41.6% in Group 3 and 69.2% in Group 4. Adhesion
      formation in Group 1 was significantly less than that in Group 4 (p = 0.001). AFS
      scores in Groups 1-4 were 0.38+/-1.02, 4.58 +/- 7.02, 0.83 +/- 1.99 and 8.53 +/-
      8.79 (mean +/- S.D.), respectively. Group 1 had the lowest AFS score and the
      difference between Group 1 and Group 4 was significant (p < 0.0001). The AFS
      score in Group 3 was also significantly less than that of Group 4 (p = 0.0009).
      CONCLUSION: Seprafilm was highly effective and was superior to the other
      antiadhesion materials tested in preventing uterine adhesions after myomectomy.

PMID- 15950365
TI  - Prevalence of high-risk human papillomavirus (HR-HPV) types 16 and 18 in healthy
      women with cytologically negative Pap smear.
AB  - OBJECTIVE: To study the prevalence of high-risk human papillomavirus (HR-HPV)
      types 16 and 18 in healthy women with negative Pap smears in identifying women
      with underlying cervical squamous intra-epithelial (SIL) lesions. METHODS: A
      total of 3300 women who were attending the Gynecology OPD of Lok Nayak Hospital,
      one of the major government tertiary hospitals in New Delhi, were screened during
      a 1-year study period, and 2079 (63%) of them were found to have cytologically
      negative Pap smear with inflammation and the rest (37%) also had negative Pap
      report but without inflammation. Hundred and sixty of these sexually active women
      aged between 20 and 60 years were randomly selected, and were investigated by
      colposcopy and a guided biopsy was done wherever required. HPV types 16 and 18
      DNA was detected in scraped cervical cells from all women using type-specific
      primers in polymerase chain reaction (PCR). RESULTS: The high-risk HPV (type 16
      and 18) prevalence by PCR was found to be 10% (16/160). Histopathological
      findings were obtained in 123 women, out of which 15 had LSIL and four had HSIL.
      High-risk HPV types 16/18 could be detected in nine out of these 19 (47.3%)
      squamous intra-epithelial lesions (p < 0.00008) which includes two out of the
      four women (50%) having HSIL, while only seven out of 104 (6.7%) of the subjects
      with normal (negative) Pap reports (p = 0.03) had infection of high-risk HPV.
      CONCLUSION: The results indicate that about 10% of women who show a negative Pap
      smear, but have inflammation are positive for high-risk HPV types 16/18 and about
      15% harbor squamous intra-epithelial lesions. It is suggested that high-risk HPV
      detection can be utilized as an adjunct to routine cytology screening programs to
      identify 'high risk' women who have concurrently negative Pap smears but may
      harbor oncogenic HPV infection and/or more likely to develop CIN lesions.

PMID- 15950367
TI  - Conservative treatment of cervical intraepithelial neoplasia using a cold-knife
      section technique.
AB  - OBJECTIVE: The purpose of this study was to evaluate a conservative cold-knife
      section technique for treatment of cervical intraepithelial neoplasia (CIN). This
      procedure can be adapted to patient age, preservation of childbearing potential
      and extent of dysplasia. DESIGN: Prospective study. SETTING: Gynecological
      Oncology Department in French Public Hospital. POPULATION: A total of 460 women
      treated for CIN between 1985 and 1999 were included. METHODS: A conservative cold
      knife cervical section followed by blanket suture reconstruction was used in all
      cases. MAIN OUTCOME MEASURES: Immediate operative results, recurrence and
      reproductive function were assessed. RESULTS: The mean length of the cervical
      specimen was 11.4 mm (range, 4-22 mm). Mean specimen thickness was strongly
      correlated with age: 10.6 +/- 4.1 mm in women <40 years versus 12.1 in women >40
      years; p < 0.001. Complete excision was achieved in 395 cases (85.8%). Post
      operative bleeding was observed in 5 cases (1.1%). The mean duration of follow-up
      was 62 months (range, 12.3-156.5 months). Recurrences developed in 26 patients
      (6.6%) including CIN 1 in 9 cases, CIN 2 in 9 and CIN 3 in 8. No patient
      developed carcinoma. The actuarial risk of recurrence was 2.4% (+/- S.D., 0.9) at
      24 months and 7.8% (+/-S.D., 1.9) at 60 months. A total of 52 pregnancies were
      observed in 39 patients. No case of de novo infertility was reported post
      operatively. Amenorrhea was noted in 1 patient (0.1%) and dysmenorrhea in 1
      patient (0.1%). CONCLUSIONS: This conservative cold-knife section technique is
      effective for treatment of CIN with low morbidity and little adverse effect on
      childbearing potential. Exposure of the squamocolumnar junction (SCJ) greatly
      facilitates follow-up.

PMID- 15950366
TI  - Lipid peroxidation and antioxidant activity in patients in labor with
      nonreassuring fetal status.
AB  - OBJECTIVE: The aim of our study was to evaluate lipid peroxidation products and
      antioxidant enzyme activity in placental tissue and umbilical cord blood, as a
      marker for fetal hypoxia in patients in labor with nonreassuring fetal status.
      STUDY DESIGN: Umbilical cord arterial blood and placental tissue samples were
      collected from 24 patients with term pregnancies in labor and nonreassuring fetal
      heart rate (FHR) patterns (study) and 24 women with normal pregnancies in labor
      and normal FHR tracings (controls) for determination of malondialdehyde (MDA) as
      a marker for lipid peroxidation and superoxide dismutase (SOD) for the
      antioxidant activity. Measured values were compared statistically between two
      groups using independent samples t-test or Mann-Whitney U-test. RESULTS: The
      median 1min Apgar score was 8 (range 4-9) in the study group and 9 (range 8-10)
      in the control group, respectively (p < 0.001). There was no statistically
      significant difference between study and control groups in terms of mean 5 min
      Apgar scores (p > 0.05). Placental MDA levels in patients with nonreassuring
      fetal status were found to be significantly elevated compared to the control
      group (12.14 nmol/g tissue versus 9.75 nmol/g tissue; p < 0.01). The placental
      SOD activity in the study group was significantly higher (p < 0.01) compared to
      controls (3.57 U/mg protein versus 2.63 U/mg protein). The umbilical cord blood
      MDA levels in the study group were higher than in normal pregnancies (4.99
      nmol/mL, 3.88 nmol/mL; p < 0.05). The activity of SOD in umbilical cord blood was
      significantly higher (p < 0.001) in patients with nonreassuring fetal status when
      compared with the control group (11.62 versus 6.95 U/mL). CONCLUSION: Lipid
      peroxidation products and antioxidant functions were elevated in the umbilical
      cord blood and placenta of patients having nonreassuring FHR tracings during
      labor. These findings indicate that lipid peroxidation products in placenta and
      umbilical cord blood can be used as a possible marker for fetal hypoxia during
      labor and SOD levels may discriminate acute from chronic hypoxia. Further
      investigations are needed with large number of series to clarify the variations
      of lipid peroxidation and antioxidant activity due to acute or chronic fetal
      hypoxia.

PMID- 15950368
TI  - Comparison of zygote intrafallopian tube transfer and transcervical uterine
      embryo transfer in patients with repeated implantation failure.
AB  - OBJECTIVE: This study was designed to evaluate the role of zygote intrafallopian
      transfer (ZIFT) procedure in patients with repeated failure of implantation.
      STUDY DESIGN: A total of 141 ZIFT cycles of 132 women and 145 embryo transfer
      (ET) cycles of 97 women in whom five or more embryos were transferred were
      included in this study. Transcervical uterine embryo transfer and ZIFT cycle
      outcome in patients with five or more previous implantation failure were
      compared. Embryos were transferred by laparoscopy into the fallopian tube 24-27 h
      following oocytes retrieval in the ZIFT group. In the ET group, embryos were
      transferred transcervically on the third day following oocytes retrieval.
      RESULTS: The mean age was 34+/-4.9 and 34.9+/-5.0 years in ZIFT and ET group,
      respectively. No difference was determined between the two groups regarding the
      basal FSH, E2 value on the day of HCG injection and the number of oocytes
      retrieved or fertilized. The implantation rate was 6.5% versus 7.2%, clinical
      pregnancy rate was 22.7% versus 24.8% and live birth rate was 21.2% versus 16.5%
      in ZIFT and ET groups, respectively. CONCLUSIONS: Implementation of ZIFT
      procedure in patients with repeated implantation failure is not superior to
      transcervical uterine embryo transfer.

PMID- 15950369
TI  - Comparison of maternal satisfaction following vaginal delivery after caesarean
      section and caesarean section after previous vaginal delivery.
AB  - OBJECTIVES: To compare (i) satisfaction levels among women who delivered
      vaginally after one previous caesarean (VBAC) with women delivered by caesarean
      after previous vaginal delivery (CSAVD) and (ii) to assess reasons why women may
      request caesarean delivery on subsequent pregnancies. STUDY DESIGN: We conducted
      a prospective questionnaire-based study of maternal satisfaction following both
      modes of delivery during an 8-month period. RESULTS: One hundred and forty women
      completed an early postnatal questionnaire, 70 each in VBAC and CSAVD cohorts.
      The vast majority in both groups were satisfied with their respective mode of
      delivery, but would opt for vaginal delivery in their next pregnancy (89% in VBAC
      versus 94% in CSAVD). The VBAC group experienced minimal pain after delivery and
      had felt better prepared for delivery (74% versus 41% in the CSAVD group).
      Reasons for dissatisfaction in the VBAC group included the physical stress of
      labour and inadequacy of analgesia. CONCLUSION: Maternal satisfaction with
      vaginal delivery is high. Those who have experienced both modes of delivery would
      prefer vaginal birth on future pregnancies. These findings are reassuring to
      women contemplating vaginal delivery.

PMID- 15950370
TI  - The relation of breech presentation at term to epilepsy in childhood.
AB  - OBJECTIVE: To investigate the relation between breech at term and epilepsy in
      childhood, and identify risk factors for epilepsy in term breech infants. STUDY
      DESIGN: Register-based study of all (n = 7514) singleton term infants without
      malformations, born between 1980 and 1994 and hospitalised with epilepsy until
      year 1996. For each case delivered in breech presentation (n = 290), the two
      subsequent deliveries of non-malformed, singleton infants delivered in breech
      presentation at term at the same hospital were selected as controls (n = 580).
      RESULTS: Breech presentation was a risk factor for epilepsy (OR: 1.2 [95% CI:
      1.1, 1.3]). Breech infants with epilepsy were more often small for gestational
      age (9.7%) than breech infants without epilepsy (4.7%). Vaginal delivery was
      associated with low Apgar score, but mode of delivery and low Apgar score were
      not related to epilepsy. CONCLUSION: The increased risk of epilepsy in term
      breech infants is not related to intrapartum events, but to growth restriction in
      pregnancy.

PMID- 15950371
TI  - The potential importance of nut removal by rodents from Australian macadamia
      orchards.
AB  - Extensive crop damage due to rodents, predominantly the black rat (Rattus rattus)
      is a major concern to both the Hawaiian and Australian macadamia industries.
      Within Australian systems, indicated the importance of adjacent non-crop habitats
      in the damage process with damage being directly related to the size and temporal
      stability of these habitats. It was also suggested that the current estimates of
      crop loss might be underestimates as R. rattus may remove nuts into adjacent non
      crop habitats, however, the economic significance of nut removal was not
      investigated. This study has determined that the crop loss due to nut removal is
      equivalent to the crop loss due to in-crop feeding within the first row of the
      orchard, with nuts being removed and consumed under the cover provided by weedy
      adjacent habitats. Previous studies (White et al.,1997; Horskins et al.,1998;
      White et al.,1998) investigating the impact of rodents on crop damage have
      ignored the nut removal component of the damage process and hence rodents have a
      far greater impact on the Australian macadamia industry than previously
      suggested. This study also indicates that the cost-benefit of habitat
      manipulation as a rodent management strategy is much greater than that suggested
      by . Habitat manipulation is not only a cost-effective means of damage control
      but is also sustainable, having none of the potentially adverse public health and
      environmental effects of continual rodenticide use.

PMID- 15950372
TI  - 1 kb of 5' flanking sequence from mouse MC4R gene is sufficient for tissue
      specific expression in a transgenic mouse.
AB  - The melanocortin 4 receptor (MC4R) plays a critical role in the regulation of
      energy homeostasis, and the MC4R knockout mouse and humans with MC4R defective
      mutations in only one allele indicate that there is a gene dosage effect.
      Alterations in gene expression levels for MC4R could, therefore, have significant
      effects on energy homeostasis. To begin to develop a mouse model for studies on
      MC4R promoter in situ we used approximately 1 kb mouse MC4R promoter together
      with 426 bp MC4R 5' UTR, previously shown to support basal expression of reporter
      gene transcription in cell lines with endogenous MC4R mRNA, and fused this DNA to
      a nuclear localized LacZ reporter gene. The construct was injected into pronuclei
      from FVB mice. Five transgenic lines were identified as carrying autosomal
      transgene insertions; three of these had significant beta-galactosidase staining
      in brain and in a few cells in the heart but not in kidney, liver, lung, gonadal
      fat or testis. The pattern of transgene expression in the brain differed markedly
      for the three lines, and in one of these lines was remarkably similar to
      endogenous MC4R mRNA expression observed using in situ hybridisation. In
      conclusion, approximately 1 kb mouse MC4R promoter is sufficient to direct gene
      expression to the brain including regions that express endogenous MC4R mRNA.

PMID- 15950373
TI  - Differential effects of estrogen receptor antagonists on pituitary lactotroph
      proliferation and prolactin release.
AB  - Anti-estrogens act by inhibiting estrogen receptor (ER) function. Unlike
      raloxifene and tamoxifen which exhibit both antagonist and agonist properties,
      ICI 182,780 (ICI) is considered a "pure" anti-estrogen devoid of any agonistic
      activities. Whereas there is ample information on the effects of anti-estrogens
      on the breast and uterus, little is known about their action on the pituitary,
      the estrogen-sensitive master endocrine gland. Our objectives were to: (1)
      compare the effects of ICI, tamoxifen and raloxifene on lactotroph proliferation
      in the absence of estrogen, (2) determine whether their action is mediated
      through the ER, and (3) compare their effects on prolactin (PRL) release. We are
      reporting that ICI is a potent inhibitor of lactotroph proliferation (both GH3
      and MMQ cells) with maximal inhibition of 45-50% seen with 1nM. ICI is several
      orders of magnitude more potent than raloxifene while tamoxifen has no effect.
      Neither anti-estrogen affects T47D breast cancer cell proliferation. GH3 cell
      incubation with ICI for 1h only causes maximal suppression of cell proliferation,
      an effect which is reversed by co-incubation with estrogen. Such a short exposure
      to ICI is sufficient to cause rapid and persistent downregulation of ERalpha
      protein, whereas downregulation of ERbeta is significantly delayed; tamoxifen and
      raloxifene have no appreciable effects on ER(s) levels. The ability of ICI to
      inhibit GH3 cell proliferation is dependent upon ERalpha, since an ERalpha, but
      not ERbeta, specific agonist reverses the effect of ICI. PRL release is
      differentially regulated by the anti-estrogens. ICI at 0.1nM suppresses PRL
      release from GH3 cells by 80%, with a similar strong suppression also seen with
      10nM raloxifene. However, tamoxifen at 0.01nM inhibits PRL release but has no
      effect at 10nM. Cell co-incubation with ICI and estradiol results in a four-fold
      increase in PRL release. Taken together, our study shows that ICI, in the absence
      of exogenous estrogens, inhibits lactotroph proliferation and PRL release by
      downregulating or inactivating ERalpha. The dissimilar responses of cell
      proliferation and PRL release to the anti-estrogens suggest that both processes
      are regulated by different mechanisms. These data highlight the importance of
      studying the effects of anti-estrogens in multiple systems.

PMID- 15950374
TI  - Exposure to light-at-night increases the growth of DMBA-induced mammary
      adenocarcinomas in rats.
AB  - In order to assess whether light exposure at night influences the growth of
      mammary tumors, as well as the role of melatonin in this process, female rats
      bearing DMBA-induced mammary adenocarcinomas were exposed to different lighting
      environments. Animals exposed to light-at-night, especially those under a
      constant dim light during the darkness phase, showed: (a) significantly higher
      rates of tumor growth as well as lower survival than controls, (b) higher
      concentration of serum estradiol, and (c) lower nocturnal excretion of 6
      sulfatoxymelatonin, without there being differences between nocturnal and diurnal
      levels. These results suggest that circadian and endocrine disruption induced by
      light pollution, could induce the growth of mammary tumors.

PMID- 15950375
TI  - Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis.
AB  - Bloom syndrome (BS) displays one of the strongest known correlations between
      chromosomal instability and an increased risk of malignancy at an early age. The
      prevention of genomic instability and cancer depends on a complex network of
      pathways induced in response to DNA damage and stalled replication forks,
      including cell-cycle checkpoints, DNA repair, and apoptosis. Several studies have
      demonstrated that BLM is involved in the cellular response to DNA damage and
      stalled replication forks. BLM interacts physically and functionally with several
      proteins involved in the maintenance of genome integrity and BLM is redistributed
      and/or phosphorylated in response to several genotoxic stresses. The data
      concerning the relationship between BLM and these cellular pathways are
      summarized and the role of BLM in the rescue of arrested replication forks is
      discussed. Moreover, I speculate that BLM deficiency is lethal, and that BLM
      deficient cells escaping apoptotic death do so by constitutively inducing a
      bacterial SOS-like response including the induction of alternative replication
      pathway(s) dependent on recombination, contributing to the mutator and hyper-Rec
      phenotypes characteristic of BS cells. This mechanism may be dependent on the
      RAD51 gene family, and involved in carcinogenesis in the general population.

PMID- 15950376
TI  - Antitumor activity of imatinib mesylate in neuroblastoma xenografts.
AB  - Imatinib mesylate has antitumor activity in vitro and in vivo against
      neuroblastoma cell lines and xenografts characterized by a different expression
      of receptor tyrosine kinases. In this article, we report that imatinib tumor
      concentration can be independent of the administered dose and does not correlate
      with the antitumor effect. In xenografts, high-dose administration does not
      improve imatinib efficacy. In conclusion, there is no clear-cut correlation
      between the levels of expression for imatinib-responsive targets and the in vitro
      and in vivo sensitivity. This further suggests that in neuroblastoma the
      antitumor activity of imatinib may involve the inhibition of other tyrosine
      kinases and/or pathways.

PMID- 15950378
TI  - Toxic gas clouds: effects and implications of dry deposition on concentration.
AB  - The influence of the dry deposition process on concentration pertaining to toxic
      gas clouds was investigated by model calculations. Three main release scenarios
      were simulated, with nine micrometeorological cases considered for each. To
      compare and confirm the results, two model types, a stochastic particle model and
      a box-type model, were independently used to simulate many of the different
      cases. The results showed that the effects of dry deposition may be strong for
      releases at, or confined close to the ground, e.g. neutral or unstable
      stratification can cause higher concentrations than stable stratification after
      10-15 km. Risk distances are in turn affected and may be substantially shortened,
      e.g. for a zero-height release like that from an evaporating pool, a 50%
      reduction in total airborne substance may occur within 500 m at a low wind
      velocity and neutral or stable stratification.

PMID- 15950377
TI  - Development of an inverse method to identify the kinetics of heavy metal release
      during waste incineration in fluidized bed.
AB  - This paper deals with the emission of heavy metals (HM) during the incineration
      of municipal solid waste in a fluidized bed reactor. This study focused on the
      development of a general method to identify the kinetics of vaporization of heavy
      metals from the on-line analysis of exhaust gas. This method is an inverse
      method, which requires only the time evolution of the HM concentration in exhaust
      gases (experimental data) and a global bubbling bed model developed for transient
      conditions at the reactor scale. First, a lab-scale fluidized bed incinerator was
      set-up to simulate the HM release during the thermal treatment of metal-spiked
      model wastes. A specific on-line analysis system based on ICP-OES was developed
      to measure in real time the variation of the relative concentration of HM in
      exhaust gases. Then, a two-phase flow bubbling bed model was developed and
      validated to calculate the kinetics of vaporization of HM from its measured
      concentration time profile in the outlet gas. The technique was first validated
      with model waste (metal-spiked mineral matrices), thus enabling at each time both
      solid sampling for measuring the HM vaporization kinetic and on-line analysis for
      measuring the HM concentration in the outlet gas. The inverse method was then
      applied to realistic artificial wastes (derived from real wastes) to identify the
      HM vaporization kinetics from the on-line analysis results.

PMID- 15950379
TI  - Mass-balance estimation of heavy metals and selected anions at a landfill
      receiving MSWI bottom ash and mixed construction wastes.
AB  - An estimation of the heavy metal and anion mass-balance was made for municipal
      solid waste incinerator bottom ash deposited at a construction and industrial
      waste landfill. The mass-balance was found by comparing the content of metals and
      anions in the landfill leachate to the metal and anion content in the deposited
      bottom ash. The discharge of heavy metals ranged from 0.001% for Pb to 0.55% for
      Cr, which is approximately at the same level as in regular municipal solid waste
      (MSW) landfills. Landfilled organic material and silicates from construction
      waste might have contributed to the retention of metals. Chloride, and to a
      lesser extent sulphate, appeared to be readily released from the landfill. It was
      estimated that a mass corresponding to 80% of the Cl- and 18% of the SO(4)2- in
      the bottom ash was discharged annually. Low retention, especially of chloride,
      may lead to a rapid decline in the discharge of this ion in the future when the
      landfilling of bottom ash is discontinued.

PMID- 15950380
TI  - Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in
      the rat.
AB  - The TRPV1 capsaicin receptor is a non-selective cation channel localized in the
      cell membrane of a subset of primary sensory neurons and functions as an
      integrator molecule in nociceptive/inflammatory processes. The present paper
      characterizes the effects of SB366791, a novel TRPV1 antagonist, on capsaicin
      evoked responses both in vitro and in vivo using rat models. SB366791 (100 and
      500 nM) significantly inhibited capsaicin-evoked release of the pro-inflammatory
      sensory neuropeptide substance P from isolated tracheae, while it did not
      influence electrically induced neuropeptide release. It also decreased capsaicin
      induced Ca2+ influx in cultured trigeminal ganglion cells in a concentration
      dependent manner (0.5-10 microM) with an IC50 of 651.9 nM. In vivo 500 microg/kg
      i.p. dose of SB366791 significantly inhibited capsaicin-induced hypothermia,
      wiping movements and vasodilatation in the knee joint, while 2 mg/kg capsazepine
      was ineffective, its effect lasted for 1h. However, neither antagonist was able
      to inhibit capsaicin-evoked hypothermia in Balb/c mice. Based on these data
      SB366791 is a more selective and in vivo also a more potent TRPV1 receptor
      antagonist than capsazepine in the rat therefore, it may promote the assessment
      of the therapeutic utility of TRPV1 channel blockers.

PMID- 15950381
TI  - Light response differences in the superior colliculus of albino and pigmented
      rats.
AB  - Multi-unit visual responses to light intensities ranging from -6.46 to 0.81
      logcd/m2 were recorded from the surface of the superior colliculus of dark
      adapted normal pigmented and normal albino rats. Light sensitivity was
      significantly higher in albinos. The response onset latency was inversely
      proportional to the stimulus intensity. The progression of the stimulus intensity
      versus response onset latency curve showed a considerable difference between
      pigmented and albino rats. At low light levels, longer response onset latencies
      were recorded in pigmented rats than in albinos. This can be attributed to the
      transmission of rod-driven responses. The differences observed in the light
      response characteristics of albino rats may be indicative of their visual
      abnormalities.

PMID- 15950382
TI  - D-Serine uptake by isolated retinas is consistent with ASCT-mediated transport.
AB  - Uptake of the neuromodulator D-serine by isolated larval tiger salamander
      (Ambystoma tigrinum) retinas was measured using capillary electrophoresis (CE).
      Excised retinas were incubated in Ringer's solution in the presence of 5 microM D
      serine. The supernatant was removed after 30 min, mixed with 4-fluoro-7-nitrobenz
      2-oxa-1,3-diazole (NBD-F) to fluorescently label amines and analyzed using CE.
      Significant D-serine uptake was observed over a period of 1.5h. This is the first
      observation of D-serine uptake by an intact retinal tissue. D-Serine uptake in
      the retina was Na(+)-dependent and blocked by l-alanine, l-threonine, and l
      cysteine. This pharmacology is consistent with the sodium dependent
      heteroexchange expected of system ASC-type transporters.

PMID- 15950383
TI  - Very low helminth infection in sheep grazed on pastures fertilised by sewage
      sludge or cattle slurry.
AB  - Helminth infection acquired by lambs grazing on pastures fertilised either by
      urban sewage sludge or cattle slurry were studied in temperate Central Western
      France. The aim was to assess the risk of larval cestodoses in lambs after sewage
      application and of digestive tract nematode infection following the slurry
      application. Twenty-six sheep were allocated on two paddocks of 0.7 ha, one
      fertilised with sludge and the other with cattle slurry. The delay between
      application and actual grazing was 6 weeks; grazing on these paddocks extended
      from mid July to beginning of November 2002. The herbage biomass was slightly
      increased in the sludge paddock but it did not result in an increase of lamb live
      weight, compared with the slurry paddock. The lambs did not acquire cysticercosis
      or any other larval cestodoses in the sewage sludge group and only very limited
      infections with Cooperia spp. and Nematodirus spp. were observed in the slurry
      group. It was concluded that in our conditions the helminth risk was extremely
      low and was not a cause of restriction of the use of these biowastes.

PMID- 15950384
TI  - Effect of Paecilomyces lilacinus on the viability of oncospheres of Taenia
      hydatigena.
AB  - Paecilomyces lilacinus (Thom) Samson is a saprophytic hyphomycete from the soil
      with biological activity on helminth eggs. We evaluated the influence in vitro of
      P. lilacinus on the viability of the oncospheres from Taenia hydatigena, a
      parasite cestode of dogs and sheep. The eggs were exposed to the fungus strain in
      sterile distilled water and observed by light microscopy at days 4, 7 and 14 post
      inoculation, and the viability was evaluated. The viability found in the exposed
      P. lilacinus oncospheres was significantly different in all observations. P.
      lilacinus exercised a negative biological activity on T. hydatigena eggs in
      vitro.

PMID- 15950385
TI  - Fate of prions in soil: trapped conformation of full-length ovine prion protein
      induced by adsorption on clays.
AB  - Studying the mechanism of retention of ovine prion protein in soils will tackle
      the environmental aspect of potential dissemination of scrapie infectious agent.
      We consider the surface-induced conformational changes that the recombinant ovine
      prion protein (ovPrP) may undergo under different pH conditions when interacting
      with soil minerals of highly adsorptive capacities such as montmorillonite. The
      conformational states of the full-length ovine prion protein adsorbed on the
      electronegative clay surface are compared to its solvated state in deuterated
      buffer in the pD range 3.5-9, using FTIR spectroscopy. The in vitro pH-induced
      conversion of the alpha-helical monomer of ovPrP into oligomers of beta-like
      structure prone to self-aggregation does not occur when the protein is adsorbed
      on the clay surface. The conformation of the trapped ovPrP molecules on
      montmorillonite is pH-independent and looks like that of the ovPrP solvated state
      at pD higher than 7, suggesting the major role of Arg and Lys residues in the
      electrostatic origin of adsorption. The uneven distribution of positively and
      negatively charged residues of the ovPrP protein would promote a favored
      orientation of the protein towards the clay, so that not only the basic residues
      embedded in the N-terminal flexible part but also external basic residues in the
      globular part of the protein might participate to the attractive interaction.
      From these results, it appears unlikely that the interaction of normal prions
      (PrP(C)) with soil clay surfaces could induce a change of conformation leading to
      the pathogenic form of prions (PrP(Sc)).

PMID- 15950386
TI  - Oxygen radicals photo-induced by ferric nitrilotriacetate complex.
AB  - This study examined the photo-induced generation of reactive oxygen species (ROS)
      by the carcinogenic iron(III)-NTA complex. Iron(III)-NTA complex (1:1) has three
      conformations (type (a) in acidic conditions of pH 1-6, type (n) in neutral
      conditions of pH 3-9, and type (b) in basic conditions of pH 7-10) with two pK(a)
      values (pK(a1) approximately 4, pK(a2) approximately 8). The iron(III)-NTA
      complex was reduced to iron(II) under cool-white fluorescent light without the
      presence of any reducing agent, and the reduction rates of the three
      conformations of iron(III)-NTA were in the order type (a)>type (n)>type (b) as
      reported previously (Akai K. et al., Free Radic. Res. 38, 951-962, 2004). ROS
      generation was investigated by electron paramagnetic resonance (EPR) spectroscopy
      with a spin-trapping technique. Apparent EPR signals attributed to PBN/*(13)CH(3)
      and PBN/*OCH(3) spin adducts were observed after incubation of the iron(III)-NTA
      complex was mixed with alpha-phenyl-tert-butylnitrone (PBN) and (13)C-DMSO in an
      aerobic condition. The addition of catalase effectively attenuated the PBN
      adducts, but superoxide dismutase enhanced them. Taken together, these results
      indicate that the iron(III)-NTA complex is spontaneously reduced to the iron(II)
      NTA complex by light under acidic to neutral pH, and in turn transfers an
      electron to molecular oxygen to form ROS.

PMID- 15950387
TI  - Isolation of SFRS3 gene and its differential expression during metamorphosis
      involving eye migration of Japanese flounder Paralichthys olivaceus.
AB  - Both eyes of flatfishes are located on one side of the body due to asymmetrical
      eye migration. The molecular mechanisms underlying such asymmetry is poorly
      understood. As an initial step, we have adopted suppression subtractive
      hybridization for the identification of upregulated genes during metamorphosis
      involving eye migration in Japanese flounder, Paralichthys olicaceus. One of the
      upregulated genes was identified as the splicing factor arginine/serine rich-3
      (SFRS3). Sequence analysis of SFRS3 revealed that it encodes a protein of 168
      amino acids containing the typical eukaryotic RNA recognition motif (RRM) and an
      arginine/serine-rich region. The overall amino acid sequences of the Japanese
      flounder SFRS3 was highly conserved with that of other organisms. The expression
      of flounder SFRS3 gene increased sharply from the beginning of metamorphosis and
      reached a high level of expression at stage H of metamorphosis 43 days after
      hatching. The SFRS3 gene upregulation was mainly limited to the head region,
      particularly in the rapidly proliferative tissues, the lateral ethmoid and "skin
      thickness" on blind side, which are thought as two proliferative tissues to push
      the eye movement. In spite of the upregulated expression of SFRS3 during
      metamorphosis, its role in metamorphosis involving eye migration requires further
      studies.

PMID- 15950388
TI  - Ascididemin and meridine stabilise G-quadruplexes and inhibit telomerase in
      vitro.
AB  - Ascididemin and Meridine are two marine compounds with pyridoacridine skeletons
      known to exhibit interesting antitumour activities. These molecules have been
      reported to behave like DNA intercalators. In this study, dialysis competition
      assay and mass spectrometry experiments were used to determine the affinity of
      ascididemin and meridine for DNA structures among duplexes, triplexes,
      quadruplexes and single-strands. Our data confirm that ascididemin and meridine
      interact with DNA but also recognize triplex and quadruplex structures. These
      molecules exhibit a significant preference for quadruplexes over duplexes or
      single-strands. Meridine is a stronger quadruplex ligand and therefore a stronger
      telomerase inhibitor than ascididemin (IC50=11 and >80 muM, respectively in a
      standard TRAP assay).

PMID- 15950389
TI  - An evaluation of sensorimotor integration during locomotion toward a target in
      Parkinson's disease.
AB  - Recent research suggests that basal ganglia dysfunction may result in problems
      integrating concurrent vision and proprioception during movement. We evaluated
      dopaminergic system involvement in this sensorimotor process during locomotion
      within a large sample of Parkinson's disease (PD) patients while "On" and "Off"
      their dopaminergic medications (n=25), in conditions that selectively manipulated
      the availability of proprioception, vision or both. The present experiment
      focused on two main objectives: i) to examine the relative influence of visual
      and proprioceptive inputs on locomotion and target accuracy in patients with PD;
      and ii) to examine the influence of dopamine replacement therapy on sensorimotor
      integration while moving toward the target. All participants walked at a self
      selected pace on a GAITRite carpet in two baseline conditions (light and dark),
      as well as four experimental darkness conditions: a) to a remembered target (i.e.
      proprioception only), b) to a remembered target with light on chest for body
      position awareness (proprioception plus), c) with vision of a lit target, also
      with light on chest (vision and proprioception), d) pushed in wheelchair to
      remembered target (no proprioception or vision). Final position was measured by 2
      D radial error, and revealed a group by condition interaction, suggesting that PD
      patients "Off" their medications move to targets with less accuracy, but approach
      the accuracy of healthy participants when in the "On" state. Both PD and healthy
      improved their accuracy with availability of concurrent vision and proprioception
      (condition c). Interestingly, our results demonstrate that PD "Off" performed the
      task with greater difficulty than when "On" medication, but only when
      proprioception was the sole source of feedback. Since PD, whether medicated or
      unmedicated were even more affected when proprioception was removed (wheelchair),
      a memory-related explanation can be ruled out. Our results suggest that the basal
      ganglia are not specifically involved in visuoproprioceptive integration;
      however, assimilation of proprioceptive feedback to guide an ongoing movement may
      be a critical function of the basal ganglia.

PMID- 15950390
TI  - A new view on hypocortisolism.
AB  - Low cortisol levels have been observed in patients with different stress-related
      disorders such as chronic fatigue syndrome, fibromyalgia, and post-traumatic
      stress disorder. Data suggest that these disorders are characterized by a symptom
      triad of enhanced stress sensitivity, pain, and fatigue. This overview will
      present data on the development, mechanisms and consequences of hypocortisolism
      on different bodily systems. We propose that the phenomenon of hypocortisolism
      may occur after a prolonged period of hyperactivity of the hypothalamic-pituitary
      adrenal axis due to chronic stress as illustrated in an animal model. Further
      evidence suggests that despite symptoms such as pain, fatigue and high stress
      sensitivity, hypocortisolism may also have beneficial effects on the organism.
      This assumption will be underlined by some studies suggesting protective effects
      of hypocortisolism for the individual.

PMID- 15950391
TI  - Depressive disorders -- is it time to endorse different pathophysiologies?
AB  - Enhanced activity of the hypothalamic-pituitary-adrenal (HPA) axis, involving
      elevated secretion of corticotropin-releasing hormone (CRH), is considered a key
      neurobiological alteration in major depression. Enhanced CRH secretion is also
      believed to contribute to the typical sleep alterations and the clinical
      presentation of major depression. While it is acknowledged that HPA overdrive and
      hypernoradrenergic function is associated with melancholic depression, there is
      growing evidence that hypoactivity of the HPA axis and afferent noradrenergic
      pathways is present in patients with atypical features of depression. The
      clinical relevance of such a differentiation is highlighted by findings which
      suggest distinct responses to pharmacological treatments. Moreover, it has been
      reported that female patients respond better to selective serotonin re-uptake
      inhibitors (SSRI) than tricyclic antidepressants. Interestingly, the female
      predominance among patients with depression seems to be restricted to the
      atypical subtype. Besides HPA axis activity, distinct alterations of the
      serotonergic system may also play a critical role for the melancholic and
      atypical phenotypes, namely a reduced restrained via 5-HT(1A) autoreceptors in
      the former and primarily reduced serotonin synthesis in the latter. Moreover,
      there is evidence for an immune activation in patients with depression, the
      extent and duration of which may be distinguishable for the melancholic and the
      atypical subtype. In this regard, lessons can be learned from depressive symptoms
      in patients with autoimmune disease, associated with different alterations of the
      HPA axis, and in patients undergoing cytokine therapy. In conclusion, the
      available data today suggest that clinically relevant differences in the
      underlying pathophysiology in patients with depression exist. The identification
      of distinct endophenotypes for major depression will not only improve our
      understanding of the disease, but will also contribute to more specific treatment
      strategies.

PMID- 15950392
TI  - A review of computer and Internet-based interventions for smoking behavior.
AB  - This article reviews studies of computer and Internet-based interventions for
      smoking behavior, published between 1995 and August 2004. Following electronic
      and manual searches of the literature, 19 studies were identified that used
      automated systems for smoking prevention or cessation, and measured outcomes
      related to smoking behavior. Studies varied widely in methodology, intervention
      delivery, participant characteristics, follow-up period, and measurement of
      cessation. Of eligible studies, nine (47%) reported statistically significant or
      improved outcomes at the longest follow-up, relative to a comparison group. Few
      patterns emerged in terms of subject, design or intervention characteristics that
      led to positive outcomes. The "first generation" format, where participants were
      mailed computer-generated feedback reports, was the modal intervention format and
      the one most consistently associated with improved outcomes. Future studies will
      need to identify whether certain patients are more likely to benefit from such
      interventions, and which pharmacological and behavioral adjuncts can best promote
      cessation.

PMID- 15950393
TI  - Gender differences in prevalence of drug use among high risk adolescents in
      Israel.
AB  - BACKGROUND: The use of tobacco, alcohol and illicit drugs is considered to be
      primarily a male problem. Many studies of drug use in the general population have
      reinforced this assumption. Other recent findings, however, call the extent of
      gender differences into question. METHODS: Self report data were collected from
      911 high risk adolescents who ranged from 12 to 18 years. RESULTS: Last 30 day
      use was used to compare the youth. Significant findings show girls use cigarettes
      more than boys; boys use all types of alcohol more than girls; and, boys use
      marijuana and hashish more than girls. No differences were reported in terms of
      the patterns of ecstasy, inhalants, prescription drugs, LSD, amphetamines,
      cocaine, crack cocaine, opium and heroin. Boys more than girls were inclined to
      binge drink. Boys and girls reported similar patterns of being in a car with a
      driver who had been drinking and driving a car after drinking. Boys more than
      girls take loans in order to obtain drugs; girls more than boys were able to
      acquire drugs without having to use their own money; and boys more than girls
      gambled to acquire drugs. DISCUSSION: With the exception of cigarettes, boys use
      drugs and engage in problem behavior more than girls. Underage drinking and
      driving is a serious behavior problem reported by male and female youth. This
      factor and binge drinking should be targeted as priority prevention issues.
      Gender differences in prevalence of drug use among high risk adolescents should
      be monitored to verify what may be a growing problem among female adolescents in
      the country and elsewhere (Litt, I., (2003). Drugs and adolescent girls.
      (editorial). Journal of Adolescent Health, 32, 1-2).

PMID- 15950394
TI  - Does estradiol induced inhibition of 11beta-hydroxysteroid dehydrogenase 1
      explain effects of the postmenopausal hormone replacement therapy?

PMID- 15950395
TI  - Lactoferrin-enhanced anoikis: a defense against neonatal necrotizing
      enterocolitis.
AB  - Enteral nutrition with human milk lowers the incidence of necrotizing
      enterocolitis in preterm human infants. Lactoferrin, the major whey protein in
      human milk, has many functions related to host defense against bacterial
      infection. Here, we hypothesize that lactoferrin also helps terminate bacterial
      invasion of enterocytes via a detachment-induced apoptosis called anoikis. Death
      of infected epithelia by anoikis prevents local spread of bacterial pathogens
      because the bacteria are trapped within the cell. Such infected, apoptotic and
      sloughed epithelia also cannot infect the lower gastrointestinal tract, and the
      epithelia exit the body in the stool. Currently, anoikis is a phenomenon related
      to the renewal of enterocytes, and it is not recognized as an anti-bacterial host
      defense. We suggest that anoikis of infected enterocytes is a process in which
      lactoferrin plays an important role. In a pilot study in which neonatal rats were
      pre-treated with intra-gastric recombinant human lactoferrin, we found evidence
      of epithelia with anoikis in ileal fluid after enteric infection. This finding
      was rarely seen in infected neonatal rats without pre-treatment with lactoferrin.
      Quantitative analysis of intestinal lavage specimens and quantitative stereology
      of apoptotic epithelia in this model will be required to verify the theory. We
      propose that oral use of recombinant human lactoferrin might have these
      hypothesized and other anti-bacterial effects in preterm infants, and hence, this
      protein might prevent necrotizing enterocolitis in preterm infants who cannot
      take human milk.

PMID- 15950396
TI  - Estrogen protection against coronary heart disease: are the relevant effects of
      estrogen mediated through its effects on uterus--such as the induction of
      menstruation, increased bleeding, and the facilitation of pregnancy?
AB  - Women in the age group of 20-50 are shown to have much less susceptibility to
      Coronary Heart Disease (CHD) and other atherosclerotic diseases as compared to
      men. Exact cause of which is not precisely known and estrogen is constantly shown
      to be associated with this phenomenon. Improvement of serum HDL concentration and
      improvement of endothelial functions are some of the proposed mechanisms through
      which estrogen is believed to mediate this effect. Estrogen therapy however has
      failed to protect women with bilateral oophorectomy and hysterectomy. Similarly
      inability of endogenous estrogen to protect women, who have undergone
      hysterectomy with functioning ovaries from CHD, questions the currently accepted
      mechanisms through which estrogen brings about these protective effects.
      Ineffectiveness of estrogen therapy as prophylaxis against CHD in men further
      questions the credibility of the currently accepted protective mechanisms of
      estrogen. Estrogen has variety of effects of on uterus, to induce menstruation,
      to induce bleeding, facilitative role in pregnancy, fetal growth and development.
      As these physiological effects either directly or indirectly result in loss of
      cholesterol from cardiovascular compartment, it is proposed that cholesterol
      losing effects of estrogen are more important than its presently believed
      beneficial effects. The small amount that is lost causes movement of cholesterol
      from atheroma towards plasma and thereby retards the progress of atherosclerosis.
      These cholesterol-losing effects of estrogen enable women to enjoy freedom from
      CHD during their reproductive age, as compared to men of comparable age group.
      Statistical data obtained from blood donors indirectly support the proposed
      hypothesis.

PMID- 15950397
TI  - Deliberate infection of unimmunized children by children immunized with
      attenuated [correction of attentuated] vaccines may be a cheaper preventive
      strategy.

PMID- 15950398
TI  - The role and effectiveness of bone marrow in osseous regeneration.
AB  - Autologous bone marrow serves as the richest and most readily available
      repository of progenitor cells capable of differentiating into mature bone
      forming cells. Numerous studies have demonstrated that bone marrow alone or cell
      suspensions of marrow usually diluted in culture medium affect de novo bone
      formation when implanted in soft tissue sites. Consequently, when bone marrow is
      used to enrich orthopaedic grafting matrices such as xenograft, demineralized
      bone matrix, or ceramic materials it almost invariably produces faster and more
      consistent defect healing compared to bone marrow or the carrier matrix alone
      and, in some cases, equivalent healing to autograft. This article evaluates the
      clinical effectiveness of these grafting materials for various orthopaedic
      applications such as healing long bone defects and enhancing spinal fusion
      procedures, and hypothesizes that enrichment with bone marrow is integral to
      timely and satisfactory graft incorporation. Methods such as centrifugation,
      culture expansion and selective cell retention that concentrate and deliver
      marrow-derived osteoprogenitor cells to the graft site as a means of mimicking
      more closely the consistent bone forming potential of autologous bone graft are
      also discussed.

PMID- 15950399
TI  - Weekly paclitaxel may improve locoregional recurrence by decreasing interstitial
      fluid pressure in operable node-positive breast cancer patients.

PMID- 15950400
TI  - Results of salvage radiotherapy after inadequate surgery in invasive cervical
      carcinoma patients: a retrospective analysis.
AB  - PURPOSE: To evaluate the results of salvage radiotherapy (RT) after inadequate
      surgery in patients with invasive carcinoma of the cervix. METHODS AND MATERIALS:
      Between 1996 and 2001, 105 invasive cervical carcinoma patients were treated at
      our center with external beam RT with or without intracavitary RT after having
      undergone total/subtotal hysterectomy at outside institutions. RESULTS: The
      median follow-up was 34 months. The gap between surgery and RT was 23-198 days
      (median, 80). Clinically visible residual disease was present in 81 patients
      (77.1%). Total hysterectomy had been done in 82 patients (78%) and subtotal
      hysterectomy in 23 patients (22%). The 5-year overall survival, disease-free
      survival, and pelvic control rates of all patients were 55.2%, 53.3%, and 72.4%,
      respectively. On univariate analysis, older age, total hysterectomy, hemoglobin
      level >10 g% before RT, nonsquamous histologic type, use of intracavitary RT, a
      shorter gap between surgery and RT, and the absence of, or a small volume of,
      residual disease favorably affected the outcome. The 5-year actuarial rate of
      late toxicity (Radiation Therapy Oncology Group Criteria) was 19% in the rectum,
      4.8% in the bladder, 24.8% in the skin, and 14.3% in the small intestine.
      CONCLUSIONS: Inadequate and inappropriate surgery in invasive cervical cancer
      with resulting gross residual disease is common in India. Factors such as the use
      of intracavitary RT, the correction of anemia, and a shorter gap between surgery
      and RT will enable postoperative RT to achieve acceptable results with minimal
      morbidity.

PMID- 15950401
TI  - Proton radiotherapy for orbital rhabdomyosarcoma: clinical outcome and a
      dosimetric comparison with photons.
AB  - BACKGROUND: Over 85% of pediatric orbital rhabdomyosarcoma (RMS) are cured with
      combined chemotherapy and radiation. However, the late effects of photon
      radiation compromise function and cosmetic outcome. Proton radiation can provide
      excellent tumor dose distributions while sparing normal tissues better than
      photon irradiation. METHODS AND MATERIALS: Conformal 3D photon and proton
      radiotherapy plans were generated for children treated with proton irradiation
      for orbital RMS at Massachusetts General Hospital. Dose-volume histograms (90%,
      50%, 10%) were generated and compared for important orbital and central nervous
      system structures. Average percentages of total dose prescribed were calculated
      based on the 3 dose-volume histogram levels for normal orbital structures for
      both the proton and photon plans. The percent of normal tissue spared by using
      protons was calculated. RESULTS: Seven children were treated for orbital
      rhabdomyosarcoma with proton irradiation and standard chemotherapy. The median
      follow-up is 6.3 years (range, 3.5-9.7 years). Local and distant controls compare
      favorably to those in other published accounts. There was an advantage in
      limiting the dose to the brain, pituitary, hypothalamus, temporal lobes, and
      ipsilateral and contralateral orbital structures. Tumor size and location affect
      the degree of sparing of normal structures. CONCLUSIONS: Fractionated proton
      radiotherapy is superior to 3D conformal photon radiation in the treatment of
      orbital RMS. Proton therapy maintains excellent tumor coverage while reducing the
      radiation dose to adjacent normal structures. Proton radiation therapy minimizes
      long-term side effects.

PMID- 15950402
TI  - Heterologous extracellular production of enterocin P from Enterococcus faecium
      P13 in the methylotrophic bacterium Methylobacterium extorquens.
AB  - Enterocin P (EntP), a strong antilisterial pediocin-like bacteriocin from
      Enterococcus faecium P13, was produced by Methylobacterium extorquens. For
      heterologous expression of EntP in the methylotrophic bacterium M. extorquens, a
      recombinant plasmid was constructed. The gene encoding the EntP structural gene
      (entP) was cloned into the plasmid vector pCM80, under control of the methanol
      dehydrogenase promoter (P(mxaF)), to generate plasmid pS25. When M. extorquens
      ATCC 55366 was transformed with pS25, EntP was detected and quantified in
      supernatants of the recombinant M. extorquens S25 strain by using specific anti
      EntP antibodies and a non-competitive indirect enzyme-linked immunosorbent assay
      (NCI-ELISA). Purification of EntP by hydrophobic adsorption and reverse-phase (RP
      FPLC) chromatographies, permitted recovery of active EntP from the supernatants
      of M. extorquens S25 grown in a synthetic defined medium.

PMID- 15950403
TI  - The complete nucleotide sequence and gene organization of the mitochondrial
      genome of the oriental mole cricket, Gryllotalpa orientalis (Orthoptera:
      Gryllotalpidae).
AB  - The complete nucleotide sequences of the mitochondrial genome (mitogenome) of the
      oriental mole cricket, Gryllotalpa orientalis (Orthoptera: Gryllotalpidae), were
      determined. The 15,521-bp-long G. orientalis mitogenome contains typical gene
      complement, base composition, and codon usage found in metazoan mitogenomes. The
      G. orientalis mitogenome contains the third lowest A+T content (70.5%) among the
      complete insects mt genome sequences. The initiation codon for the G. orientalis
      COI gene appears to be ATG, instead of the tetranucleotides, which have been
      postulated to act as initiation codon for Locusta migratoria and some
      lepidopteran COI genes. The initiation codon for ND2 appears to be GTG, which is
      rare, but has been designated as an initiator of Tricholepidion gertschi ND2. All
      anticodons of G. orientalis tRNAs were identical to Drosophila yakuba and L.
      migratoria. The tRNA(Ser)(AGN) could not form a stable stem loop structure in the
      DHU arm as shown in many other insect tRNA(Ser)(AGN). Phylogenetic analysis of
      nucleotide sequence information from all mt genes supported a monophyletic
      Diptera, a monophyletic Lepidoptera, a monophyletic Coleoptera, a monophyletic
      Mecopterida (Diptera+Lepidoptera), and a monophyletic Endopterygota
      (Diptera+Lepidoptera+Coleoptera), suggesting that the complete insect mitogenome
      sequence has a resolving power to the diversification events within
      Endopterygota. However, the relationships of ancient insect orders were unstable,
      indicating the limited use of mitogenome information at deeper phylogenetic
      depth.

PMID- 15950404
TI  - Evaluation of the recombinant LipL32 in enzyme-linked immunosorbent assay for the
      serodiagnosis of bovine leptospirosis.
AB  - The recombinant leptospiral protein LipL32 was evaluated for use in the diagnosis
      of bovine leptospirosis by enzyme-linked immunosorbent assay (rLipL32 IgG ELISA).
      The microscopic agglutination test (MAT) of 150 serum samples from cattle
      suspected of leptospirosis showed that 125 (83.3%) samples had positive
      reciprocal agglutination titres, which ranged from 100 to 1600. The highest
      titres were observed for the serovars Hardjoprajitno and Bratislava. In the
      rLipL32 IgG ELISA, 83.3% of the samples were positive. The sensitivity of IgG
      ELISA for 125 bovine sera, which had MAT titres of greater than or equal to 100,
      was 100%. ELISA showed a specificity of 100% with 58 bovine sera, which were
      negative at a 1:50 dilution in the MAT for Leptospira interrogans serovars. When
      analytical specificity of the IgG ELISA was evaluted using 60 bovine serum
      samples from animals showing serum antibodies to other pathogens that cause
      abortion in cattle, such as Babesia sp., Anaplasma sp. and Brucella sp. and no
      cross-reaction was observed. The recombinant LipL32 IgG ELISA can be an
      alternative to the MAT for diagnosis of leptospiral infection in cattle.

PMID- 15950405
TI  - Characterization and immuno-detection of AIDA-I adhesin isolated from porcine
      Escherichia coli.
AB  - A relatively high percentage of porcine Escherichia coli isolates from cases
      associated with neonatal and post-weaning diarrhea are positive for the gene
      encoding adhesin involved in diffuse adhesion I (AIDA-I). This gene and its
      corresponding protein were first identified and characterized in E. coli strain
      2787 isolated from human infantile diarrhea. Little is known about the properties
      of the AIDA-I protein and its immuno-detection on surface of AIDA-I positive
      porcine E. coli isolates. In this study, we demonstrated that the AIDA-I adhesin
      isolated from porcine AIDA-I positive E. coli is an acidic protein consisting of
      five isoforms. It has a similar molecular weight (100 kDa) and relatively high
      amino acid homology (78-87%) with the AIDA-I adhesin expressed by human AIDA-I
      positive E. coli strain 2787. Based on limited comparison, it appears that there
      is a very high homology among AIDA-I proteins expressed by porcine AIDA-I
      positive E. coli isolates. Sensitivity of detection of surface AIDA-I adhesin of
      PCR-positive AIDA-I E. coli by immuno-dot-blot and coagglutination tests was 76
      and 71%, respectively, whereas specificity was 89 and 84%, respectively. These
      tests are unlikely to be used for diagnostic detection of AIDA-I positive E. coli
      due to the relatively low sensitivity; however, they may be potentially useful
      for identification of false positive reactions generated by other diagnostic
      tests.

PMID- 15950406
TI  - Effects on protein and mRNA expression levels of p53 induced by fluoride in human
      embryonic hepatocytes.
AB  - We investigated the effects of protein and mRNA expression levels on p53 induced
      by fluoride in human embryo hepatocyte L-02 cells. The protein and mRNA levels of
      p53 in L-02 cells were measured after in vitro cultured L-02 was exposed to
      sodium fluoride at different doses (40, 80, and 160 microg/ml) for 24 h. The
      results showed that the cell survival rate of L-02 cells in the high dose
      fluoride group was significantly lower than that of the control group. The
      protein expression levels of p53 in the middle and high dose fluoride group were
      significantly higher than in the control group and elevated with increasing
      fluoride concentration. The mRNA expression levels of p53 in the fluoride groups
      were markedly higher than in the control group. The mRNA expression level of p53
      in the high dose fluoride group was however lower compared to the middle dose
      fluoride group, but similar to the low dose fluoride group. These finding suggest
      that fluoride can decrease the L-02 cells survival rate and induce protein and
      mRNA expressions of p53; however, there is no consistency between the protein
      expression level of p53 and the mRNA expression level.

PMID- 15950407
TI  - Environmental effects on progesterone profile measures of dairy cow fertility.
AB  - Environmental effects on fertility measures early in lactation, such as the
      interval from calving to first luteal activity (CLA), proportion of samples with
      luteal activity during the first 60 days after calving (PLA) and interval to
      first ovulatory oestrus (OOE) were studied. In addition, traditional measurements
      of fertility, such as pregnancy to first insemination, number of inseminations
      per service period and interval from first to last insemination were studied as
      well as associations between the early and late measurements. Data were collected
      from an experimental herd during 15 years and included 1106 post-partum periods
      from 191 Swedish Holsteins and 325 Swedish Red and White dairy cows. Individual
      milk progesterone samples were taken twice a week until cyclicity and thereafter
      less frequently. First parity cows had 14.8 and 18.1 days longer CLA (LS-means
      difference) than second parity cows and older cows, respectively. Moreover, CLA
      was 10.5 days longer for cows that calved during the winter season compared with
      the summer season and 7.5 days longer for cows in tie-stalls than cows in loose
      housing system. Cows treated for mastitis and lameness had 8.4 and 18.0 days
      longer CLA, respectively, compared with healthy cows. OOE was affected in the
      same way as CLA by the different environmental factors. PLA was a good indicator
      of CLA, and there was a high correlation (-0.69) between these two measurements.
      Treatment for lameness had a significant influence on all late fertility
      measurements, whereas housing was significant only for pregnancy to first
      insemination. All fertility traits were unfavourably associated with increased
      milk production. Regression of late fertility measurements on early fertility
      measurements had only a minor association with conception at first AI and
      interval from first to last AI for cows with conventional calving intervals, i.e.
      a 22 days later, CLA increased the interval from first to last insemination by
      3.4 days. Early measurements had repeatabilities of 0.14-0.16, indicating a
      higher influence by the cow itself compared with late measurements, which had
      repeatabilities of 0.09-0.10. Our study shows that early fertility measurements
      have a possibility to be used in breeding for better fertility. To improve the
      early fertility of the cow, there are a number of important factors that have to
      be taken into account.

PMID- 15950408
TI  - Modulation of post-thaw sperm functions with oviductal proteins in buffaloes.
AB  - A study was undertaken to determine the effects of oviductal proteins obtained
      from various stages of the estrous cycle on spermatozoa characteristics in
      buffaloes. Oviducts were collected from apparently healthy buffalo genital tracts
      (nonluteal and luteal stage of estrous cycle) and separated into isthmus and
      ampulla. Each segment of oviduct (nonluteal and luteal) was flushed with PBS (pH
      7.4). The flushing obtained was centrifuged (3000 rpm; 30 min), filtered (0.2
      microm) and frozen at -20 degrees C. The proteins in pooled nonluteal isthmic and
      ampullary and luteal isthmic and ampullary fluids were precipitated overnight
      using ammonium sulphate, centrifuged (10000 rpm; 30 min) and dialyzed (>10 kDa).
      After protein estimation, aliquots of samples containing 10 mg proteins were
      lyophilized in cryovials and stored in frozen form at -20 degrees C. Six pooled
      good-quality ejaculates collected by artificial vagina method from two Murrah
      buffalo bulls were utilized for the study. After fresh semen analysis, each
      pooled ejaculate was splited into five parts and extended in Tris-egg yolk
      citrate extender (20% egg yolk; 7% glycerol), so that final dilution yielded
      approximately 60 million sperm cells per ml, and cryopreserved in 0.5 ml French
      straws (30 million sperm cells/straw) in LN(2) (-196 degrees C). Before freezing,
      nonluteal isthmic and ampullary and luteal isthmic and ampullary proteins were
      incorporated at the rate of 1mg/ml of extended semen. The equilibrated and frozen
      thawed (37 degrees C for 30 s) semen was evaluated for motility, live %,
      acrosomal integrity percentage, bovine cervical mucus penetration test and hypo
      osmotic sperm swelling test. Besides this, spermatozoa from treatment and control
      groups were incubated at 37 degrees C for 6 h in sperm TALP. Among the nonluteal
      and luteal oviductal proteins, the former maintained higher (P < 0.05) post-thaw
      sperm motility, live %, and acrosomal integrity than the control group. Between
      the isthmic and ampullary proteins, the isthmic proteins incorporated group
      maintained higher (P < 0.05) post-thaw sperm motility, live %, and acrosomal
      integrity. Similarly, higher sperm penetration distance in cervical mucus was
      recorded in nonluteal isthmic proteins incorporated group. But, irrespective of
      the stage of an estrous cycle, isthmic proteins included group maintains higher
      sperm membrane integrity as revealed by higher (P < 0.05) swollen sperm
      percentage in response to hypo-osmotic solution than the ampullary proteins
      included and control groups. Similarly, at any time during incubation the sperm
      motility and viability was higher (P < 0.05) in isthmic proteins treated group
      than the ampullary and control group. But, the same trend was not observed in
      terms of acrosomal integrity percentages. It is inferred that inclusion of
      oviductal proteins in the extender prior to freezing improved post-thaw semen
      quality. Oviductal proteins differentially affected sperm function depending upon
      the region of oviduct and the stage of estrous cycle at which the proteins were
      obtained.

PMID- 15950409
TI  - Use of hormone replacement therapy in the Hong Kong public health sector after
      the Women's Health Initiative trial.
AB  - OBJECTIVES: To determine the impact of Women Health Initiative (WHI) trial on the
      use of hormone replacement therapy (HRT) in the Hong Kong public health sector.
      METHODS: The central prescription database of the Hospital Authority was used to
      describe the half-yearly trend in the use of HRT between July 2000 and December
      2003. The data of hysterectomy was retrieved from another clinical database.
      RESULTS: Before the publication of the WHI trial in July 2002, conjugated equine
      estrogens (CEE) and its related products dominated HRT prescribing. Relative to
      the first half of 2002, there was an immediate and substantial decline by 43.5%
      in the prescriptions of combined CEE/progestogen products and a modest decline by
      22.4% in the prescriptions of CEE-alone therapy in the second half of 2002. In
      the first half of 2003, a decline in the prescriptions of all HRT preparations
      except raloxifene was observed. However, in the second half of 2003, there were
      no more declines in overall HRT users. Relative to the first half of 2002, the
      decline in the overall HRT users in the first half of 2003 was more than 46% in
      women aged 50-69. The decline was greater in women with a history of hysterectomy
      (60.3%) than women without (38.6%), but was similar between gynaecology specialty
      (41.7%) and non-gynaecology specialty (43.9%). CONCLUSIONS: Similar to the U.S.,
      an immediate and substantial decline in the use of CEE and its related products
      was observed in Hong Kong after the publication of the WHI trial.

PMID- 15950410
TI  - Cardiovascular risk factors in a cohort of Danish women born in 1936 prior to use
      of hormone therapy.
AB  - OBJECTIVE: Many observational studies suggest hormone therapy protects against
      coronary heart disease in contrast to findings from large randomised clinical
      trials and an observational Danish study. A potential bias in the observational
      literature concerning the cardiovascular risk and benefits associated with use of
      hormone therapy is the so-called 'healthy user' phenomenon, i.e. self-selection
      to HT use is associated with healthier cardiovascular risk profile. This study
      investigates whether a random sample of Danish women using HT was characterised
      by a favourable cardiovascular risk profile prior to menopause. METHODS: A sample
      of 621 women born in 1936 living in Copenhagen County was included in a
      prospective population-based study initiated in 1976 with follow-ups in 1981,
      1987 and 1996. Investigations comprised questionnaires and physical examinations.
      RESULTS: At 51 and 60 years, respectively, one-third and one-half had ever used
      HT. At 40 years women who subsequently use HT had lower body mass index, lower
      self-rated health and lower fasting glucose, but no differences according to
      blood pressure, cholesterol, triglyceride, physical activity, smoking habits or
      alcohol consumption. CONCLUSION: In a cohort of Danish women from the general
      population ever users of HT could not be characterised as unambiguous 'healthy
      users'.

PMID- 15950411
TI  - A lecithin-based microemulsion of rh-insulin with aprotinin for oral
      administration: Investigation of hypoglycemic effects in non-diabetic and STZ
      induced diabetic rats.
AB  - The aim of this study was to develop a microemulsion formulation providing an
      improved efficacy of orally administered insulin. The microemulsions were
      prepared using Labrafil M 1944 CS, Phospholipon 90 G (lecithin), absolute alcohol
      and bi-distilled water. The microemulsions of recombinant human (rh)-insulin and
      aqueous solution (200 IU/kg) were administered intragastrically by a canulla to
      diabetic and non-diabetic rats. Aprotinin (2500 KIU/g) was added as the enzyme
      inhibitor to the formulation. Upon the administration of intragastric rh-insulin
      solution (IS) to non-diabetic rats, the plasma glucose and insulin levels were
      not changed significantly. Therefore, the hypoglycemic effect caused by
      subcutaneous rh-insulin solution (SC), microemulsion containing rh-insulin (IME)
      and microemulsion containing rh-insulin and aprotinin (IMEA) were analyzed in
      diabetic rats. The area above the plasma glucose levels time curves (AAC),
      minimum glucose concentration (Cmin) and time to Cmin (tmin) were derived from
      the plasma glucose profiles. IME and IMEA caused approximately 30% decrease in
      plasma glucose levels. The decrease in the plasma glucose levels continued after
      the 90th min. The highest AAC value was obtained when IMEA was administered to
      rats. The maximum plasma insulin concentration (Cmax), time to reach Cmax (tmax),
      terminal half-life (t(1/2)), area under the plasma concentration-time curve
      (AUC), mean residence time (MRT) and elimination rate constant (k(el)) values
      were also calculated. It was observed that t(1/2) values varied between 0.53 and
      1.31h. No significant difference could be found between the pharmacokinetic
      parameters of the IME and IMEA administered groups. Addition of aprotinin to the
      microemulsion containing rh-insulin increased bioavailability when compared to
      those not containing it, although the difference is not significant.

PMID- 15950412
TI  - Effect of heat-treatment and the role of phospholipases on Fungizone-induced
      cytotoxicity within human kidney proximal tubular (HK-2) cells and Aspergillus
      fumigatus.
AB  - The objectives of this study were to determine the effects of heat-treatment on
      Fungizone (FZ)-induced cytotoxicity in human kidney (HK-2) cells and fungal
      isolates of Aspergillus fumigatus, and to determine the possible role of
      phospholipases (PLA2 and PLC) on heat-treated FZ (HFZ)-associated renal cell
      toxicity. HK-2 cells were grown at 37 degrees C in T75 flasks and seeded in 96
      well plates at 20,000 cells/well. FZ and HFZ concentrations of 10, 25 and 50
      microg/mL of AmpB were prepared. Snake venom PLA2 and PLC (2.15 U/mL) were pre
      incubated with HFZ for 1h prior to addition to the cells. After 18 h of
      incubation, an MTS assay was performed to assess cell viability through
      mitochondrial respiration. A spore suspension of A. fumigatus was prepared and 96
      well plates were seeded at 500,000 spores/well. HFZ and FZ were prepared as above
      and incubated with the fungi at 35 degrees C. After 72 h, the minimum inhibitory
      concentration (MIC) was determined as the lowest concentration of drug that
      inhibited visible growth. Student-Newman-Keuls multiple comparisons tests were
      conducted to determine statistical significance. FZ-induced cytotoxicity was
      significantly greater than for HFZ in HK-2 cells at amphotericin B (AmpB)
      concentrations between 10 and 50 microg AmpB/mL (n = 5-9, p < 0.05). HFZ and FZ
      were found to have similar minimum inhibitory concentration (MIC) ranges for A.
      fumigatus (0.225-0.25 microg) AmpB/mL; (n = 6). The addition of PLA2 and PLC to
      50 microg heat-treated AmpB/mL significantly enhanced the cytotoxicity compared
      to controls (n = 6, p < 0.05). The presence of the phospholipases did not alter
      FZ-associated renal cell toxicity. Taken together, these findings suggest heat
      treatment significantly decreased FZ-induced cytotoxicity in HK-2 cells without
      altering toxicity against a reference strain of A. fumigatus. In addition, PLA2
      and PLC enhanced the renal toxicity associated with HFZ, but not that of FZ.

PMID- 15950413
TI  - Cellular and spatial changes in the anuran superior olive across metamorphosis.
AB  - In many vertebrate species, the superior olive in the auditory brainstem plays an
      essential role in sound source localization. Little is known, however, about the
      structural and functional changes in this nucleus during development when
      alterations in head size and shape as well as in inner ear projections are
      expected to affect the perception of binaural cues. Using stereological
      techniques, we investigated the changes in several cellular and spatial features
      of the bullfrog superior olive across metamorphosis, the time period during which
      the animal transforms from a totally aquatic larva to a semiterrestrial adult.
      The total number of cells shows a strongly linear increase from hatchling through
      late larval stages. The number of neurons decreases during metamorphic climax
      stages, and recovers to pre-metamorphic climax levels in the early post
      metamorphic froglet stage. The number of glial cells increases during the early
      larval period, and remains relatively stable, with no systematic variation, from
      late larval to froglet stages. The volume of the superior olive increases rapidly
      in early larval stages, followed by a much-attenuated rate of growth between late
      larval and froglet stages. These morphological changes may provide a substrate
      for the functional restructuring of the bullfrog superior olive, shortly before
      the switch from aquatic to mostly atmospheric hearing.

PMID- 15950414
TI  - Slow motility, electromotility and lateral wall stiffness in the isolated outer
      hair cells.
AB  - Slow motile length changes of isolated, apical turn outer hair cells (OHCs)
      (n=36) were induced by perfusion of saline (flow rate: 0.6 microl/min) as a
      mechanical challenge or by perfusion of 12.5 mM KCl solution for 90 s as a
      chemical and mechanical challenge with and without ocadaic acid (OA), a
      serine/threonine protein phosphatase inhibitor. Electromotility was evoked by
      square pulses from +/-35 mV to +/-240 mV during the slow shortening and recovery
      period (n=36). Stiffness of the lateral wall was measured by the micropipette
      aspiration technique (n=20). Saline perfusion caused a reversible shortening of
      774+/-87 nm (n=9) as well as K+ of 1465+/-159 nm (n=9). Slow shortening increased
      lateral wall stiffness (1.25+/-0.02 to 1.52+/-0.03 nN/microm) (n=5-5).
      Simultaneously, electromotility magnitude decreased (n=9). Ocadaic acid blocked
      slow shortening, increased lateral wall stiffness, and decreased the magnitude of
      electromotility. Mechanical or mechanical+chemical stimulation of ocadaic acid
      treated OHCs do not further change stiffness or electromotility. Isolated OHCs
      respond with slow shortening and consutive cell stiffness increase to mechanical
      insult. This phenomenon seems operating with calcium-, and phosphorylation
      dependent modifications of the cytoskeletal proteins. The subsequent
      electromotility gain decrease suggests a slow OHC shortening driven regulation of
      the cochlear amplifier with simultaneous safety control of the auditory periphery
      against overstimulation.

PMID- 15950415
TI  - Prevention of noise-induced hearing loss with Src-PTK inhibitors.
AB  - Studies from our lab show that noise exposure initiates cell death by multiple
      pathways [Nicotera, T.M., Hu, B.H., Henderson, D., 2003. The caspase pathway in
      noise-induced apoptosis of the chinchilla cochlea. J. Assoc. Res. Otolaryngol. 4,
      466-477] therefore, protection against noise may be most effective with a
      multifaceted approach. The Src protein tyrosine kinase (PTK) signaling cascade
      may be involved in both metabolic and mechanically induced initiation of
      apoptosis in sensory cells of the cochlea. The current study compares three Src
      PTK inhibitors, KX1-004, KX1-005 and KX1-174 as potential protective drugs for
      NIHL. Chinchillas were used as subjects. A 30 microl drop of one of the Src
      inhibitors was placed on the round window membrane of the anesthetized
      chinchilla; the vehicle (DMSO and buffered saline) alone was placed on the other
      ear. After the drug application, the middle ear was sutured and the subjects were
      exposed to noise. Hearing was measured before and several times after the noise
      exposure and treatment using evoked responses. At 20 days post-exposure, the
      animals were anesthetized their cochleae extracted and cochleograms were
      constructed. All three Src inhibitors provided protection from a 4 h, 4 kHz
      octave band noise at 106 dB. The most effective drug, KX1-004 was further
      evaluated by repeating the exposure with different doses, as well as,
      substituting an impulse noise exposure. For all conditions, the results suggest a
      role for Src-PTK activation in noise-induced hearing loss (NIHL), and that
      therapeutic intervention with a Src-PTK inhibitor may offer a novel approach in
      the treatment of NIHL.

PMID- 15950416
TI  - Endothelium-dependent and direct relaxation induced by ethyl acetate extract from
      Flos Chrysanthemi in rat thoracic aorta.
AB  - The aims of the present study were to investigate the vasoactive effects of ethyl
      acetate extract from Flos Chrysanthemi (FCE) and its mechanisms on the rat
      thoracic aorta. FCE (9.4-150 mg/L) caused a concentration-dependent relaxation on
      endothelium-intact rings precontracted with phenylephrine (PE, 10(-6)M) or a high
      level of K+ (6x10(-2)M). By removal of endothelium, the effect was not abolished
      but reduced significantly. N(G)-nitro-l-arginine methyl ester (l-NAME) (10(-4)
      M), methylene blue (10(-5) M) significantly inhibited the effect of FCE.
      Meanwhile, NO synthase of aorta in FCE group was markedly elevated versus the
      control. However, indomethacin did not influence FCE effect. SKF-525A combined
      with l-NAME had the same effect as l-NAME. Tetraethylammonium, BaCl2, 4
      aminopyridine, 5-HD and propranolol also did not influence the vascular effect of
      FCE, but glibenclamide significantly attenuated its vasodilation. FCE did not
      reduce PE-induced transient contraction in Ca(2+)-free medium, but inhibited PE
      induced contraction in K(+)-free solution or Ca2+ caused contraction after PE
      induced a stable contraction in Ca(2+)-free solution. It is concluded that FCE
      induced both endothelium-dependent and -independent relaxation. NO and cGMP
      mediated pathway are likely involved in the endothelium-dependent relaxation,
      whereas inhibition of voltage-dependent Ca2+ channel, receptor-operate Ca2+
      channel and activation of K(ATP) contribute in part to the endothelium
      independent relaxation.

PMID- 15950417
TI  - Spasmogenic activity and acute toxicity of Yumijangquebo, a herbal laxative
      formulation.
AB  - We evaluated the pharmacological properties and spasmogenic activities of
      Yumijangquebotrade mark, a Korean herbal laxative formulation. Doses in the range
      12-50 microg/ml induced a large spasmogenic effect in isolated guinea pig ileum,
      similar to that induced by acetylcholine. Pre-treating the tissue with atropine
      (0.2 microM) completely abolished the contractile effect of Yumijangquebo. The
      spasmogenic effect of Yumijangquebo and the inhibition of this effect by atropine
      suggest that a cholinergic mechanism is responsible for its effects.
      Yumijangquebo increased the gastrointestinal motility in ICR mice at doses
      between 10 and 37 mg/kg. Yumijangquebo exhibited higher activity than three other
      laxatives tested, which had activities about 85% of that of Yumijangquebo. In an
      acute toxicity study using Sprague-Dawley rats, the median lethal dose (LD50) of
      Yumijangquebo was greater than 2000 mg/kg, and we found no pathological changes
      in macroscopic examination by necropsy of rats treated with Yumijangquebo. We
      conclude that Yumijangquebo may be safely used as a herbal spasmogenic laxative
      agent.

PMID- 15950418
TI  - Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic
      stellate cell.
AB  - Hepatic stellate cells (HSC) play a central role in hepatic fibrosis and
      compounds that promote apoptosis in HSC may have anti-fibrotic potentials. Herbal
      medicine has long been used in chronic liver disease but there is little
      scientific evidence for their actions. The present study investigated the effects
      of 14 commonly used herbs on cellular proliferation and apoptosis of a rat
      hepatic stellate cell line, HSC-T6 and the underlying mechanism of herb-induced
      apoptosis. HSC-T6 cell were incubated with herbal extracts and their
      proliferation was assessed by colorimetric assay. Apoptosis was measured and
      confirmed by flow cytometry, terminal transferase uridyl nick end labeling
      (TUNEL) assay and morphological features in hematoxylin and eosin staining.
      Apoptotic pathways involving Fas receptor and Bcl-2 family were investigated by
      Western blot. Five herbs, namely Angelica sinensis (AS), Carthamus tinctorius
      (CT), Ligusticum chuanxiong (LC), Salvia miltiorrhiza (SM) and Stephania
      tetrandra (ST) demonstrated both anti-proliferative and pro-apoptotic activities
      in HSC-T6. The highest potency was detected in SM and ST with 51.63 and 44.52% of
      HSC-T6 showing apoptotic changes, respectively. This was associated with
      upregulation of Fas and Bax and down-regulation of Bcl-xL in HSC. Fas ligand and
      Bcl2 expressions remained unchanged. The potential anti-fibrotic effect of herbal
      medicine warrants further evaluation.

PMID- 15950419
TI  - Genitourinary tuberculosis.
AB  - Although uncommon, genitourinary tuberculosis is the most common site of
      extrapulmonary tuberculosis infection. Its diagnosis is often difficult. This
      article provides an overview of the pathologic and radiologic findings of this
      disease process.

PMID- 15950420
TI  - Tuberculosis in children.
AB  - Epidemiology of tuberculosis (TB) in childhood is closely related to TB in
      adults. Serious manifestations are often observed in children with TB.
      Immunological immaturity and social dependence facilitate the spread of
      infection. Paediatricians account in practise both primary TB, with hilar
      lymphadenopathy, and subacute or chronic pulmonary complications, in TB disease.
      Children appear to have a higher risk of having extrapulmonary TB involving any
      organ. The diagnosis of tuberculosis reactivation/re-infection, is based in the
      isolation of the agent in the sputum . Primary TB is difficult to diagnose,
      usually established by indirect signs of low epidemiological specificity,
      symptoms, chest radiography and the intracutaneous tuberculin test. In this
      context, one can understand the importance of correct interpretation of the chest
      radiograph. Chest CT is recommended if the chest radiograph is equivocal. In
      addition, an overview of extrapulmonary cases of TB - of the spine, bone and
      lymph nodes - including the role of other imaging modalities (Us and MR) will be
      presented .

PMID- 15950421
TI  - Normal variants of the intracranial circulation demonstrated by MR angiography at
      3T.
AB  - Magnetic resonance angiography (MRA) at 3T offers increased signal to noise ratio
      with better background suppression, leading to exquisite depiction of the
      intracranial circulation. We present a pictorial review of the normal variations
      and anomalies of the intracranial circulation detected on MRA performed on a high
      field 3T clinical scanner using parallel imaging techniques. The salient imaging
      features of these anomalies and normal variations are discussed with relevance to
      clinical practice.

PMID- 15950422
TI  - Characterization of different laser irradiation methods for quantitative Raman
      tablet assessment.
AB  - Quantitative Raman spectroscopy of conventional wet granulated pharmaceutical
      immediate release tablets and subsequent data evaluation was investigated.
      Different aspects of quantitative assessment of active pharmaceutical ingredient
      (API) in intact tablets with special focus on sub-sampling issues were addressed.
      Four different geometric laser irradiance patterns were examined to study the
      effect of sub-sampling within the tablets. The Raman data was evaluated using
      both univariate and multivariate techniques. UV absorbance spectroscopy was used
      as a reference method. The best result in terms of prediction error was attained
      by irradiating a large area of the tablets. Using multivariate calibration with
      multiplicative signal correction (MSC) the prediction error was 1.7%. In
      addition, the effect of tablet density on the Raman assessment was investigated.
      It was found that quantitative Raman assessment of chemical content can be made
      insensitive to variations in tablet density corresponding to a manufacturing
      compression interval of 5-20 kN provided that adequate data treatment is used. A
      short discussion about sample heating in the context of different irradiation
      patterns is included with reference to previous work. In conclusion, the present
      study provides a platform for developing an implementation strategy for
      quantitative Raman spectroscopy for both laboratory analysis and process
      analytical technology (PAT) applications.

PMID- 15950423
TI  - Determination of methyl and ethyl esters of methanesulfonic, benzenesulfonic and
      p-toluenesulfonic acids in active pharmaceutical ingredients by solid-phase
      microextraction (SPME) coupled to GC/SIM-MS.
AB  - The development, optimization and validation of an extraction method for methyl
      and ethyl esters of various sulfonic acids is presented. The extraction and
      determination of these esters in active pharmaceutical ingredients (APIs) was
      accomplished using solid-phase microextraction coupled to GC/MS in the SIM mode.
      The factors affecting the extraction efficiency are discussed. This method was
      validated as a limits test and allows the determination of the sulfonic esters at
      the 5 ppm level in APIs. The method proved to be reproducible (%R.S.D.s less than
      6%) and suitable for use with external standard quantitation, and also met basic
      validation requirements. This method offers numerous advantages over liquid
      liquid extraction methods and was also compared to other extraction techniques
      such as solid-phase extraction (SPE) and liquid-phase microextraction (LPME) also
      being developed in our laboratories.

PMID- 15950424
TI  - Solid-state study of mepivacaine hydrochloride.
AB  - Different crystalline forms of the local anaesthetic mepivacaine hydrochloride
      (MH) were revealed by Fourier transform infrared spectroscopy (FT-IR), not by
      conventional differential scanning calorimetry (DSC). The existence of two
      polymorphic anhydrous modifications was discovered and further characterized by X
      ray powder diffraction and thermal analysis: Form II, the commercial one, and the
      more stable Form I, obtained by re-crystallization from Form II. Two
      pseudopolymorphs were also obtained: Form III, a solvate crystallized from
      ethanol and Form IV, a solvate crystallized from methanol. Single crystal X-ray
      diffraction data for both solvates were collected and their structures were
      determined. Form II, metastable and monotropically related to Form I, generates
      through desolvation of Form III, very often present in industrial processing,
      where crystallization from ethanol solution is a common practice. For the sake of
      clarity, the presence of polymorphic forms should be reported in the drug master
      files of MH. However, since MH is readily water soluble, the observed
      polymorphism has no relevance to its typical clinical use as aqueous solutions.

PMID- 15950425
TI  - Simultaneous quantification of stavudine, lamivudine and nevirapine by UV
      spectroscopy, reverse phase HPLC and HPTLC in tablets.
AB  - In the present study, simultaneous quantification of stavudine (SV), lamivudine
      (LV) and nevirapine (NV) in tablets by UV spectroscopy, reverse phase HPLC (RP
      HPLC) and HPTLC methods were developed. In the UV multi-component spectral
      method, SV, LV and NV was quantified at 266, 271 and 315 nm, respectively. In the
      RP-HPLC method, the drugs were resolved using a mobile phase of 20 mM sodium
      phosphate buffer (containing 8 mM 1-octanesulphonicacid sodium salt):acetonitrile
      (4:1, v/v) with pH adjusted to 3.5 using phosphoric acid on a C18-ODS-Hypersil (5
      microm, 250 mm x 4.6 mm) column in isocratic mode. The retention time of SV, LV
      and NV was 2.85, 4.33 and 8.39 min, respectively. In the HPTLC method, the
      chromatograms were developed using a mobile phase of chloroform:methanol (9:1,
      v/v) on precoated plate of silica gel 60 F254 and quantified by densitometric
      absorbance mode at 265 nm. The Rf of SV, LV and NV were 0.21-0.27, 0.62-0.72 and
      0.82-0.93, respectively. Recovery values of 99.16-101.89%, percentage relative
      standard deviation of <0.7 and correlation coefficient (linear dynamic range) of
      0.9843-0.9999 shows that the developed methods were accurate and precise. These
      methods can be employed for the routine analysis of tablets containing SV, LV and
      NV.

PMID- 15950426
TI  - Optimization of gas chromatographic method for the enantioseparation of
      arylpropionic non-steroidal anti-inflammatory drug methyl esters.
AB  - The gas chromatography (GC) method for enantioseparation of well-known non
      steroidal anti-inflammatory drugs ibuprofen, fenoprofen and ketoprofen methyl
      esters mixture was developed. Best enantioseparation was performed on capillary
      column with heptakis-(2,3-di-O-methyl-6-O-t-butyldimethyl-silyl)-beta
      cyclodextrin stationary phase and hydrogen used as a carrier gas. Initial
      temperature, program rate and carrier pressure were optimized to obtain best
      resolution between enantiomers.

PMID- 15950427
TI  - Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by
      NF-kappaB.
AB  - Chemokines, or chemotactic cytokines, are major regulators of the inflammatory
      response and have been identified as pathogenic factors in the periprosthetic
      soft tissue. Particulate wear debris induced NF-kappaB activation, the major
      transcriptional regulator of IL-8 and MCP-1 pro-inflammatory genes and, indeed,
      both IL-8 and MCP-1 chemokine gene expressions were upregulated in titanium
      particulate-stimulated human osteoblasts. Here, we demonstrate that phagocytosed
      particles activate the IL-8 gene promoter via a NF-kappaB-mediated mechanism.
      Transfection of a dominant negative mutant IkappaBalpha protein that cannot be
      serine phosphorylated led to suppression of IL-8 promoter activity. The p65/RelA
      NF-kappaB subunit activity was affected in both a time- and titanium particle
      concentration-dependent fashion. Titanium particles led to increased ERK, JNK,
      and p38 activation in MG-63 osteoblast cells, and IL-8 protein release was
      suppressed by specific inhibitors of the ERK and p38 MAPK pathways. Together, our
      results suggest that wear debris particles induce chemokine expression in
      osteoblasts via NF-kappaB-mediated transcriptional activation, which is
      controlled by the MAPK signal transduction pathway.

PMID- 15950428
TI  - Physiology of the periparturient period and its relation to severity of clinical
      mastitis.
AB  - Incidence of clinical mastitis is highest at drying off and during the
      periparturient period. Intramammary Escherichia coli infection in high-yielding
      cows can show a severe clinical response during the early post-partum period.
      Severe clinical mastitis is mainly determined by cow factors, in particular the
      functionality of the circulating polymorphonuclear leukocytes (PMN) which are
      recruited to the mammary gland during the inflammatory reaction. There is a co
      incidence between the periods of highest incidence of clinical mastitis and
      specific structural changes in the mammary gland. During the periparturient
      period, marked changes in various systemic and local hormones are related to the
      secretory state of the mammary gland epithelium (lactogenesis). Estrogen and
      progesterone induce proliferation of the mammary epithelium throughout gestation
      and act as survival factors in different tissues, although conflicting data have
      been reported on their effect on PMN oxidative burst. Somatotropin (STH),
      responsible for maintenance of lactation in ruminants, has been shown to
      positively influence innate immunity and a more rapid recovery in milk production
      of severely affected animals. The concentration of STH, and as a result also IGF
      I levels is, however, quite low during early lactation. IGF-I and its regulating
      binding proteins are associated with cell survival, modulation of apoptosis and
      functionality of PMN in humans. During early lactation, bio-availability of IGF-I
      is decreased, which might reduce its stimulating effects on PMN quality and
      functionality. PRL, concomitantly known as a lactogenic hormone and an
      immunoregulatory cytokine, has also been associated with modulation of the immune
      system. It is expected that in periparturient animals, hormone changes could
      interfere with the immune response and the clinical response of mastitis.

PMID- 15950429
TI  - Oocyte-somatic cell-endocrine interactions in pigs.
AB  - Oocyte-somatic cell communication is bi-directional and essential for both oocyte
      and follicular granulosa and theca cell function and development. We have shown
      that the oocyte secretes factors that stimulate porcine granulosa cell
      proliferation in serum-free culture, and suppress progesterone production,
      thereby preventing premature luteinisation. Possible candidates for mediating
      some of these effects are the bone morphogenetic proteins (BMPs) that belong to
      the transforming growth factor beta family. They are emerging as a family of
      proteins critical for fertility and ovulation rate in several mammals, and they
      are expressed in various cell types in the ovary. We have evidence for a
      functional BMP system in the porcine ovary and BMP receptors are present in the
      egg nests in the fetal ovary and in the granulosa cells, oocytes and occasional
      theca cells throughout subsequent development. In addition to paracrine
      interactions in the ovary, the porcine oocyte and its developmental potential can
      also be influenced by nutritional manipulation in vivo. We have demonstrated that
      feeding a high plane of nutrition to gilts for 19 days prior to ovulation
      increased oocyte quality compared to control animals fed a maintenance diet, as
      determined by oocyte maturation in vitro. This was associated with a number of
      changes in circulating reproductive and metabolic hormones and also in the
      follicular fluid in which the oocyte is nurtured. Further studies showed a
      similar increase in prenatal survival on Day 30 of gestation, demonstrating a
      direct link between oocyte quality/maturation and embryo survival. Collectively,
      these studies emphasise the importance of the interactions that occur between the
      oocyte and somatic cells and also with endocrine hormones for ovarian
      development, and ultimately for the production of oocytes with optimal
      developmental potential.

PMID- 15950430
TI  - Role of tumor necrosis factor-alpha and nitric oxide in luteolysis in cattle.
AB  - Although prostaglandin (PG) F2alpha is known to be a principal luteolytic factor,
      its action on the bovine corpus luteum (CL) is mediated by other intra-ovarian
      factors. Tumor necrosis factor-alpha (TNFalpha) and its specific receptors are
      present in the bovine CL with the highest expressions at luteolysis. TNFalpha in
      combination with interferon-gamma reduced progesterone (P4) secretion, increased
      PGF2alpha and leukotriene C4 (LTC4) production, and induced apoptosis of the
      luteal cells in vitro. Low concentrations of TNFalpha caused luteolysis, which
      resulted in a decreased level of P4, and increased levels of PGF2alpha, LTC4 and
      nitrite/nitrate (stable metabolites of nitric oxide-NO) in the blood. Inhibition
      of local NO production counteracts spontaneous and PGF2alpha-induced luteolysis.
      Therefore, NO is a likely candidate for the molecule that mediates PGF2alpha and
      TNFalpha actions during luteolysis. Both PGF2alpha and TNFalpha increase NO
      concentrations in blood, and stimulate NO synthase expression on protein level in
      the bovine CL cells. NO stimulates PGF2alpha and LTC4 secretion, inhibits P4
      production and reduces the number of viable luteal cells. TNFalpha and NO induce
      apoptotic death of the CL by modulating expression of bcl-2 family genes and by
      stimulating expression and activity of caspase-3. The above findings indicate
      that TNFalpha and NO play crucial roles in functional and structural luteolysis
      in cattle.

PMID- 15950431
TI  - Early embryonic administration of xenoestrogens alters vasotocin system and male
      sexual behavior of the Japanese quail.
AB  - The copulatory behavior and the parvocellular vasotocin (VT) system of the
      nucleus of the stria terminalis (BST) are sexually dimorphic in the Japanese
      quail. Embryonic administration of estradiol benzoate (EB) induces an
      organizational effect determining the disappearance of such a dimorphism (male
      shows behavior and cerebral phenotype of the female). The VT parvocellular system
      can therefore be considered an accurate marker of the sexual differentiation of
      brain circuits and a very sensitive indicator of the activity of estrogen-like
      substances on neural circuits. To test this hypothesis we administered
      diethylstilbestrol (DES), a powerful synthetic xenoestrogen, genistein (GEN), a
      phytoestrogen produced by soy, and bisphenol A (BPA). After 3 days of incubation,
      quail eggs were injected with vehicle, EB, DES, GEN or BPA. Administration of BPA
      caused an early blockage of development and no further analyses were done on the
      BPA groups. At puberty, the copulatory behavior of EB- or DES-treated male quail
      was totally abolished, whereas only the highest doses of GEN determined a
      significant decrease of the behavior. After the tests, the animals were
      sacrificed and perfused. The fractional area (FA) covered by VT immunoreactivity
      was analyzed in BST, medial preoptic nucleus, and lateral septum by computerized
      image analysis. The FA was significantly reduced after treatment with EB, DES and
      GEN at high doses. These results confirm that the sexually dimorphic VT system of
      the Japanese quail is a sensible indicator of the effects of xenoestrogens at the
      level of the central nervous system.

PMID- 15950432
TI  - Microvascular distribution and vascular endothelial growth factor expression in
      bovine cystic follicles.
AB  - The aim of this study was to examine the distribution of microvessels in the
      theca and the expression of vascular endothelial growth factor (VEGF) in the
      theca and granulosa of cystic follicles. Paraffin sections of cystic follicles
      were stained with Bandeiraea simplicifolia-I (BS-I) to visualize the endothelial
      cells of microvessels. The other sections were immunostained with anti-VEGF
      antibody. The mRNA expression of VEGF in the theca interna of cystic and healthy
      follicle was determined by RT-PCR. In the theca interna, cystic follicles with
      granulosa cells had significantly greater microvessel number density (the number
      of microvessels per given field) and area (area occupied by microvessels per
      given area) than healthy follicles in various sizes (<3, 4-8, >9 mm). Loss of
      granulosa cells from cystic follicles resulted in a similar number density, but
      significantly smaller area of microvessels in the theca interna. There was no
      significant difference in the microvessel number density and area of the theca
      externa between the types of follicle. VEGF protein was expressed in the
      granulosa and theca interna of healthy and cystic follicles. These results
      demonstrate that cystic follicles have a highly developed vasculature network in
      the theca interna, especially in cystic follicles containing granulosa cells. It
      is also suggested that VEGF is highly expressed in the cystic follicle as well as
      healthy follicle, which may be associated with advanced vasculature and the
      accumulation of follicular fluid in cystic follicles.

PMID- 15950433
TI  - Screening for androgen receptor activities in 253 industrial chemicals by in
      vitro reporter gene assays using AR-EcoScreen cells.
AB  - Recently, there has been great concern about the potential of industrial
      chemicals to act as endocrine disrupters. In this report, we conducted a pilot
      study to validate the use of AR-EcoScreen cells for tier 1 screening of androgen
      receptor (AR) agonist and antagonist activities. From 253 test compounds, we
      identified two AR agonists and nine antagonists. The two agonists, 2-tert
      butylanthraquinone and benzoanthrone, were relatively weak (10% maximal
      activation of the positive control, 5alpha-dihydrotestosterone, at 2.54x10(-7)
      and 4.46x10(-6) M, respectively). The most potent antagonist was 3,3'
      dichlorobenzidine dihydrochloride (IC50 = 2.28x10(-7) M). The order of the anti
      androgenic activities was 3,3'-dichlorobenzidine dihydrochloride>4
      diethylaminobenzaldehyde>4,4'-[1-[4-[1-(4-hydroxyphenyl)-1
      methylethyl]phenyl]ethylidene]bis[phenol]>2,4,6-trichlorophenylhydrazine = 4
      (phenylpropyl)pyridine>2-hydroxy-4-methoxybenzophenone>2,2-bis(4
      cyanophenyl)propane>4-methoxy-2-methyldiphenylamine = 2,4-diphenyl-4
      methylpentene-1. These results suggest that AR-EcoScreen cell line has the
      potential to be used as a tool for the large scale tier 1 screening of chemicals
      for androgen receptor agonist and antagonist activity.

PMID- 15950434
TI  - Interpreting expression profiles of cancers by genome-wide survey of breadth of
      expression in normal tissues.
AB  - A critical and difficult part of studying cancer with DNA microarrays is data
      interpretation. Besides the need for data analysis algorithms, integration of
      additional information about genes might be useful. We performed genome-wide
      expression profiling of 36 types of normal human tissues and identified 2503
      tissue-specific genes. We then systematically studied the expression of these
      genes in cancers by reanalyzing a large collection of published DNA microarray
      datasets. We observed that the expression level of liver-specific genes in
      hepatocellular carcinoma (HCC) correlates with the clinically defined degree of
      tumor differentiation. Through unsupervised clustering of tissue-specific genes
      differentially expressed in tumors, we extracted expression patterns that are
      characteristic of individual cell types, uncovering differences in cell lineage
      among tumor subtypes. We were able to detect the expression signature of
      hepatocytes in HCC, neuron cells in medulloblastoma, glia cells in glioma, basal
      and luminal epithelial cells in breast tumors, and various cell types in lung
      cancer samples. We also demonstrated that tissue-specific expression signatures
      are useful in locating the origin of metastatic tumors. Our study shows that
      integration of each gene's breadth of expression (BOE) in normal tissues is
      important for biological interpretation of the expression profiles of cancers in
      terms of tumor differentiation, cell lineage, and metastasis.

PMID- 15950435
TI  - Compulsive behavior in Prader-Willi syndrome: examining severity in early
      childhood.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia
      and food preoccupations. Researchers indicate that individuals with PWS,
      including young children, exhibit food and non-food-related compulsions.
      Normative rituals are also often present among typically developing preschoolers.
      However, it is unclear how these behaviors affect the child. Although
      preschoolers with PWS exhibit more types of rituals than other populations, it is
      uncertain if the severity of these behaviors differs from the rituals experienced
      during normative development. Thus, the purpose of this research was to determine
      whether the ritualistic behaviors exhibited by preschoolers with PWS differ in
      severity from those exhibited during normative development. We also sought to
      identify whether non-food ritualistic behavior was related to the hyperphagia in
      PWS. Parents of 68 children with PWS, 86 typically developing children, and 57
      children with developmental delays completed questionnaires on rituals and eating
      behavior. Children with PWS exhibited more severe ritualistic behavior than
      typically developing children but not other children with developmental delays.
      However, the severity of non-food-related rituals was related to the severity of
      eating behavior in PWS. We hypothesize that this link between hyperphagia and non
      food-related compulsivity may share a common underlying neurobiological
      mechanism.

PMID- 15950436
TI  - Quality of life during treatment with haloperidol or olanzapine in the year
      following a first psychotic episode.
AB  - OBJECTIVES: Schizophrenia causes significant impairments of quality of life. As
      treatment approaches have advanced, more attention has been given to re
      integrating patients into their psychosocial environments, rather than simply
      monitoring psychotic symptoms. The development of the second-generation
      antipsychotics raised hope that these medications would provide better quality of
      life improvement than conventional antipsychotics. This improvement is
      particularly relevant early in the course of schizophrenia. METHODS: To address
      these considerations, improvements in measures of general health and social
      function (determined using the SF-36) were assessed in 195 patients with first
      episode schizophrenia for up to one year following randomization to either
      olanzapine or haloperidol in a double blind clinical trial. We hypothesized that
      olanzapine would demonstrate better improvement on these measures than
      haloperidol. In order to test this hypothesis, we used a repeated measure model
      with SF-36 scores as the outcome, and treatment group, time, time2, time-by
      treatment group interaction, and time2-by-treatment group interaction as fixed
      effects. RESULTS: Both treatments demonstrated similar changes on the SF-36.
      Independent of treatment, patients demonstrated significant improvements in most
      of the SF-36 subscales, which approached normative scores by the end of one year
      of treatment. Forty-six of 100 olanzapine-treated patients and 37 of 95
      haloperidol-treated patients completed the one year of this study (p<.4).
      CONCLUSIONS: These results suggest an important initial treatment goal for
      patients with new onset schizophrenic disorders, namely that they can expect to
      recover significant quality of life and social function at least initially in
      treatment.

PMID- 15950437
TI  - Prefrontal cognitive functions in stabilized first-episode patients with
      schizophrenia spectrum disorders: a dissociation between dorsolateral and
      orbitofrontal functioning.
AB  - Specific prefrontal cognitive impairments have been reported in first-episode and
      chronic schizophrenia. We sought to investigate potential impairments in specific
      prefrontal cortical cognitive functions among stabilized patients with a first
      episode of schizophrenia. A sample of 80 individuals with a first-episode of
      schizophrenia spectrum disorders and 22 healthy volunteers underwent a
      neurocognitive battery assessing orbitofrontal (OFC) [The Iowa Gambling Task
      (GT)], and dorsolateral prefrontal (DLPFC) functions (WAIS III Backward digits,
      verbal fluency test (FAS), and Trail Making Test). Cognitive data were obtained
      following stabilization of acute psychotic symptoms. Clinical symptoms after six
      weeks of treatment were assessed by using the SAPS and SANS scales. While there
      were no significant group differences in overall scores and in the profile of
      progress of performance along periods on the GT, patient group showed a
      significant impairment when performing DLPFC tasks. Only FAS score was correlated
      to the severity of negative symptomatology. The OFC functions are unimpaired at
      the early phases of psychosis and in contrast there is a significant deficit in
      DLPFC functions in first-episode of schizophrenia.

PMID- 15950438
TI  - Behavioral signs of schizoidia and schizotypy in social anhedonics.
AB  - Social anhedonia appears to be a promising indicator of Meehl's construct of
      schizotypy. While findings from diagnostic, cognitive, and psychophysiological
      studies have supported the validity of social anhedonia as an indicator of
      schizotypy, the behavioral characteristics of these putative schizotypes are not
      yet fully understood. This study utilized a rating system for behavioral signs of
      schizoidia and schizotypy to determine whether atypical interpersonal behaviors
      were observable in social anhedonics and to examine if these behavioral signs
      provide unique information, beyond traditional symptom ratings, in the
      identification of putative schizotypes. A community sample of 170 18-19-year-olds
      (85 social anhedonics, 85 controls) received diagnostic evaluations which were
      videotaped and subsequently rated for behavioral signs of schizoidia and
      schizotypy. Compared to controls, the social anhedonia group displayed
      significantly more behavioral signs characteristic of schizoid and schizotypal
      personality disorders. Behavioral signs of schizoidia accounted for a significant
      amount of group variance even after controlling for clinical symptom ratings.
      These results indicate that social anhedonics display interpersonal behaviors
      consistent with risk for schizophrenia-spectrum disorders and that these
      behavioral signs convey information about group status that is not accounted for
      by traditional clinical interview ratings of symptomatology.

PMID- 15950439
TI  - In vitro activity of linezolid against multidrug-resistant Mycobacterium
      tuberculosis isolates.
AB  - Information in the literature regarding the activity of linezolid against
      multidrug-resistant (MDR) Mycobacterium tuberculosis strains is scarce. We
      therefore tested the in vitro activity of this drug against 39 MDR M.
      tuberculosis strains isolated from clinical specimens using the Bactec 460 TB
      system. All strains were inhibited by < or = 8 mg/L (minimum inhibitory
      concentration (MIC); MIC50 = 4 mg/L, MIC90 = 8 mg/L). Although the MIC values are
      higher than in other studies, based on proposed breakpoints all strains were
      found to be susceptible to linezolid. Further investigations to prove its
      usefulness in the treatment of MDR tuberculosis should be carried out.

PMID- 15950440
TI  - Dissociation between the locomotor and anxiolytic effects of acetaldehyde in the
      elevated plus-maze: evidence that acetaldehyde is not involved in the anxiolytic
      effects of ethanol in mice.
AB  - Acetaldehyde, the first product of ethanol metabolism, has been suggested to play
      a major role in many behavioral effects of ethanol. However, very few studies
      have directly tested the behavioral effects of the acute administration of
      acetaldehyde. In particular, the role of this metabolite in ethanol-induced
      anxiolytic effects has never been extensively tested. The aim of the present
      study was to characterize the anxiolytic effects of acetaldehyde in two strains
      of mice, C57BL/6J and CD1 mice with the elevated plus-maze procedure. The results
      show that acute injections of ethanol (1-2 g/kg) induced significant dose
      dependent anxiolytic effects in both strains of mice. In contrast, acetaldehyde
      failed to produce any anxiolytic effect, although it induced a significant
      hypolocomotor effect at the highest doses. In an independent experiment,
      cyanamide, an aldehyde dehydrogenase inhibitor, prevented the locomotor stimulant
      effects of ethanol, although it failed to alter its anxiolytic effects. Together,
      the results of the present study indicate that acetaldehyde is not involved in
      ethanol-induced anxiolytic effects, although it may be involved in its
      sedative/hypolocomotor effects.

PMID- 15950441
TI  - Size and burden of depressive disorders in Europe.
AB  - We review epidemiological studies of depression in Europe. Community surveys are
      essential. Methodological differences in survey methods, instruments, nuances in
      language and translation limit comparability, but consistent findings are
      emerging. Western European countries show 1 year prevalence of major depression
      of around 5%, with two-fold variation, probably methodological, and higher
      prevalences in women, the middle-aged, less privileged groups, and those
      experiencing social adversity. There is high comorbidity with other psychiatric
      and physical disorders. Depression is a major cause of disability. Incidence has
      been less studied and lifetime incidence is not clear, with longitudinal studies
      required. There is pressing need for prevalence studies from Eastern Europe. The
      considerable differences in health care systems among European countries may
      impact on proportions of depressives receiving treatment and its adequacy,
      particularly in the key area of primary care, and require further study. There is
      a need for public health programmes aimed at improving treatment, reducing rates
      and consequences of depressive disorders.

PMID- 15950442
TI  - Functional effects of single dose first- and second-generation antipsychotic
      administration in subjects with schizophrenia.
AB  - Using PET with (15)O water, we characterized the time course of functional brain
      changes following the acute administration of a first- and a second-generation
      antipsychotic. Volunteers with schizophrenia were scanned while drug-free
      (baseline) and after single dose administration of haloperidol (n=6) or
      olanzapine (n=6) during a time course adapted to their plasma kinetics. To obtain
      brain location information, we contrasted each post-drug scan to baseline
      acquired scans. We plotted the regional cerebral blood flow (rCBF) extracted in
      these locations and calculated the kinetic characteristics of the curves.
      Further, we compared and contrasted the rCBF changes induced by the drugs over
      the first 4 h post-drug administration. Dorsal and ventral striatum, thalamus and
      anterior cingulate cortex were activated with haloperidol, while frontal,
      temporal and cerebellum regions evidenced reduced flow. With olanzapine, ventral
      striatum, anterior cingulate and temporal cortices evidenced increases, and
      thalamus and lingual cortex decreases, in rCBF. Both drugs activated the caudate
      nucleus. Haloperidol induced greater activation of the dorsal striatum than did
      olanzapine. These data reveal important differences in patterns of brain
      activation between the drugs. Differences in the involvement in basal ganglia
      parallel known differences between the drugs in the emergence of acute EPS upon
      emergency administration.

PMID- 15950443
TI  - Effect of lipophilic counter-ions on membrane diffusion of benzydamine.
AB  - Many topically applied drugs are ionized molecules that exhibit poor penetration
      across the lipid domains of the stratum corneum. Reduction of the charge on the
      molecule would be expected to enhance skin penetration. The objective of this
      study was to investigate the interaction of the non-steroidal anti-inflammatory
      drug benzydamine hydrochloride with suitable counter-ions including ibuprofen
      sodium. The influence of pH of the donor solution and hence degree of ionization
      on partitioning between n-octanol:buffer and the flux of benzydamine
      hydrochloride across polydimethyl siloxane (PDMS) membrane and human epidermis
      was determined. The maximum flux was determined at pH 7.6 when the fraction
      unionized was 2.51%, rather than at pH 9 when the fraction unionized was 38.7%.
      This suggests that at higher pH, although the permeability coefficient is
      increased, the decrease in solubility and therefore concentration of dissolved
      benzydamine in the medium results in a decrease in flux across the PDMS membrane.
      Ion-pair formation or interaction with each of the counter-ions was confirmed by
      NMR spectroscopy. Significant increases in logP and flux across PDMS membrane
      were determined for the ion-pairs (0.087, 12.54, 11.31, 0.121 microg cm(-2)h(-1)
      for benzydamine hydrochloride and ion-pairs with ibuprofen sodium, sodium
      benzoate and sodium octane sulfonate respectively). This study shows that it is
      possible to significantly enhance the flux of salts across a lipophilic membrane
      in the presence of counter-ions, resulting from intermolecular interaction and/or
      ion-pair formation.

PMID- 15950444
TI  - Ex vivo analysis of T-cell function.
AB  - Our ability to analyze T-cell function in vitro has progressed in recent years to
      include analysis of early signaling events, such as specific protein
      phosphorylation, intermediate functions, such as degranulation and cytokine
      production, and later functions, such as proliferation. Many assays are now
      available to monitor these events, and comparative studies of some of these
      assays have been published. Major recent developments in this area include the
      ability to measure T-cell degranulation via cell surface exposure of CD107 and
      the use of polychromatic flow cytometry to examine multiple phenotypes and
      functions of responding T cells.

PMID- 15950445
TI  - Vaccinology at the beginning of the 21st century.
AB  - Today, the main challenges for vaccinologists include improving vaccines against
      as yet undefeated pathogens, rapid identification and response to emerging
      diseases and successful intervention in chronic diseases in which ongoing immune
      responses are insufficient. Reverse genetics and reverse vaccinology are now used
      to generate rapidly new vaccine strains and to mine whole genomes in the search
      for promising antigens. The rational design of adjuvants has become possible as a
      result of the discovery of the receptors that recognize microbial patterns and
      lead to dendritic cell activation. Antigen-loaded dendritic cells, DNA in naked,
      formulated or viral form, and other delivery systems are used to maximize immune
      responses. Although work on the 'easy' vaccines has already been completed, it is
      hoped that a combination of conceptual and technical innovation will enable the
      development of more complex and sophisticated vaccines in the future.

PMID- 15950446
TI  - NOD proteins: an intracellular pathogen-recognition system or signal transduction
      modifiers?
AB  - NOD1 and NOD2 are members of a diverse family of cytoplasmic proteins that
      contain C-terminal leucine-rich repeats. Because of their similarity to a family
      of plant proteins involved in pathogen resistance, and because mutations in
      Card15, encoding NOD2, are frequently found in familial cases of Crohn's disease-
      an intestinal malady of excessive inflammation--NOD proteins have been proposed
      to fulfill a role in the intracellular sensing of bacteria. Indeed, NOD proteins
      seem to alter the ability of cells to respond to fragments from bacterial cell
      walls. This system could function analogously to the Toll-like receptors-
      extracellular proteins that play an essential role in pathogen recognition.
      However, the idea of an intracellular system that specifically recognizes
      bacterial cell components is controversial and alternative functions of NODs are
      possible including regulating signal transduction systems.

PMID- 15950447
TI  - Pathogen recognition with Toll-like receptors.
AB  - The innate immune system is an evolutionarily conserved system of defense against
      microbial infections. The family of Toll-like receptors is a major class of
      receptors that sense molecular patterns associated with a broad range of
      pathogens including bacteria, viruses, fungi and protozoa. Following pathogen
      recognition, Toll-like receptors initiate intracellular signal transduction that
      results in the expression of genes involved in inflammation, antiviral responses
      and maturation of dendritic cells. Individual Toll-like receptors activate common
      and unique transcription factors through different signaling pathways to drive
      specific biological responses against microorganisms.

PMID- 15950448
TI  - Gene profiling of immune responses against tumors.
AB  - Clinical trials of tumor-antigen-specific immunization have clearly shown that
      immune-mediated tumor rejection requires more than simple T cell-target cell
      interactions. In vivo generation of tumor-specific T cells is one of a series of
      steps necessary for the induction of clinically relevant immune responses. In
      recent years, high-throughput functional genomics exposed the complexity of tumor
      immune biology, which underlies the kaleidoscopic array of variables associated
      with cancer instability and immunogenetic variability in humans. In the quest to
      understand immune rejection, hypothesis-driven approaches have failed to take
      into account the intricacy of human pathology by relying mostly on hypotheses
      derived from experimental models rather than direct clinical observation. Future
      investigations should reframe scientific thinking when applied to humans,
      utilizing descriptive tools to generate novel hypotheses relevant to human
      disease.

PMID- 15950449
TI  - Pathogenesis of severe acute respiratory syndrome.
AB  - Severe acute respiratory syndrome (SARS) is a zoonotic infectious disease caused
      by a novel coronavirus (CoV). The tissue tropism of SARS-CoV includes not only
      the lung, but also the gastrointestinal tract, kidney and liver. Angiotensin
      converting enzyme 2 (ACE2), the C-type lectin CD209L (also known L-SIGN), and DC
      SIGN bind SARS-CoV, but ACE2 appears to be the key functional receptor for the
      virus. There is a prominent innate immune response to SARS-CoV infection,
      including acute-phase proteins, chemokines, inflammatory cytokines and C-type
      lectins such as mannose-binding lectin, which plays a protective role against
      SARS. By contrast there may be a lack of type 1 interferon response. Moreover,
      lymphopenia with decreased numbers of CD4+ and CD8+ T cells is common during the
      acute phase. Convalescent patients have IgG-class neutralizing antibodies that
      recognize amino acids 441-700 of the spike protein (S protein) as the major
      epitope.

PMID- 15950450
TI  - Interactions between malaria parasites and the host immune system.
AB  - Malaria remains one of the greatest impediments to development in many tropical
      regions of the world. Understanding host immune responses to malaria parasites is
      crucial for the effective design and implementation of new vaccines and drugs.
      Recent research has seen the identification of the first pattern recognition
      receptor (TLR9) on dendritic cells for a defined product of malaria infection
      (hemozoin). In addition, progress has been made in understanding the role of
      dendritic cell subsets in malaria, and how they promote specific components of
      the host immune response. Potentially important advances in vaccine design have
      also been made by inserting a Plasmodium sporozoite epitope into the yellow fever
      vaccine 17D, as well as using a whole, live-attenuated sporozoite vaccine.

PMID- 15950451
TI  - Levels of complexity in pathogen recognition by C-type lectins.
AB  - In pathogen recognition by C-type lectins, several levels of complexity can be
      distinguished; these might modulate the immune response in different ways.
      Firstly, the pathogen-associated molecular pattern repertoire expressed at the
      microbial surface determines the interactions with specific receptors. Secondly,
      each immune cell type possesses a specific set of pathogen-recognition receptors.
      Thirdly, changes in the cell-surface distribution of C-type lectins regulate
      carbohydrate binding by modulating receptor affinity for different ligands.
      Crosstalk between these receptors results in a network of multimolecular
      complexes, adding a further level of complexity in pathogen recognition.

PMID- 15950452
TI  - Hydrophobins: proteins with potential.
AB  - Hydrophobins are self-assembling proteins of fungal origin. Their ability to self
      assemble into an amphipathic membrane is of interest for many different
      applications, ranging from medical and technical coatings to the production of
      proteinaceous glue and cosmetics. Assembled hydrophobins can modify surface
      characteristics, thus controling the binding properties of the surface; for
      example, enzymes can be actively and non-covalently immobilized on electrode
      surfaces and medical coatings can be improved for biocompatibility. Over the past
      few years research on hydrophobins has contributed to a better understanding of
      the self-assembly process and is generating more handles to control and
      manipulate the process. This knowledge could have an immediate effect on
      production levels, which are not yet adequate, and provide the boost needed for
      hydrophobins to reach their full potential.

PMID- 15950453
TI  - Protein fibers as performance proteins: new technologies and applications.
AB  - Protein fibers are fundamental building blocks of life playing an essential role
      in motility, elasticity, scaffolding, stabilization and the protection of cells,
      tissues and organisms. Despite nearly a century of research into the assembly
      mechanisms and structures of fibrous proteins, only limited information is still
      available. Within the past decade, however, insights have been provided into how
      some fibrous proteins assemble and how they function in biology. In addition,
      efforts are increasingly being made to employ protein fibers as performance
      molecules in man-made medical and technical applications.

PMID- 15950454
TI  - Cell rearrangements during development of the somite and its derivatives.
AB  - The generation of somites, and the subsequent formation of their major
      derivatives, muscle-, cartilage-, dermis- and tendon-cell lineages, is tightly
      orchestrated and, to different extents, these are also mutually supporting
      processes. They involve complex and timely reorganizations of the paraxial
      mesoderm, such as multiple phases of epithelial-mesenchymal rearrangements and
      vice-versa, cellular movements and migrations, and modifications of both cell
      shape and cell cycle properties. These morphogenetic changes are triggered by
      local environmental signals and are tightly associated to a genetic program
      imparting cell-specific fates. Elucidating these signals and their downstream
      effectors, in addition to determining the state of specification of responsive
      cell subsets and that of single progenitors in the various domains, is only
      beginning.

PMID- 15950455
TI  - Molecular mechanisms controlling germline and somatic stem cells: similarities
      and differences.
AB  - Germline and somatic stem cells are distinct types of stem cells that are
      dedicated to reproduction and somatic tissue homeostasis, respectively. Extensive
      studies on these two stem cell types in different organisms over the past few
      years have revealed some commonalities in the mechanisms controlling their self
      renewal and differentiation. Furthermore, germline or somatic cells in various
      organisms and sexes also exhibit their own unique ways of regulating stem cell
      function. By understanding these similarities and differences we might gain a
      better insight into how stem cells are regulated in general and how germline and
      somatic stem cell types are regulated differently.

PMID- 15950456
TI  - Prediction of cis-regulatory elements using binding site matrices--the successes,
      the failures and the reasons for both.
AB  - Protein-DNA interactions control many aspects of animal development and cellular
      responses to the environment. Although profiling of individual transcription
      factor binding sites is not a reliable guide for predicting the position of cis
      regulatory elements in large genomes, modelling the evolution and the
      organization of regulatory elements has provided enough information to make some
      successful predictions. For vertebrate genomes, the field is limited by the lack
      of sufficient experimental data upon which to build reliable models. Nonetheless,
      a combination of experimental, computational and comparative data is likely to
      reveal aspects of complex regulatory networks in vertebrates, just as it has
      already done for simple eukaryotic genomes.

PMID- 15950457
TI  - Pax genes in eye development and evolution.
AB  - Animal eyes with widely different anatomical designs have long been thought to
      arise independently, multiple times during evolution. This view was challenged
      about a decade ago by the landmark discoveries that Pax6, a highly conserved
      transcription factor, plays a key role in eye morphogenesis in both flies and
      mammals. Since then, more evidence has emerged in favour of the redeployment of
      Pax6 and some other developmental control genes within the genetic program
      underlying eye formation throughout the animal kingdom. Recent work has indicated
      that other members of the Pax gene family play a pivotal role in eye
      morphogenesis. The Eye gone gene regulates eye growth in Drosophila, whereas the
      PaxB gene is implicated in visual system development in jellyfish, the most basal
      organism possessing eyes.

PMID- 15950458
TI  - Epidermal impermeable barriers in mouse and fly.
AB  - Despite significant structural differences, the surface epithelia of flies and
      mice exhibit remarkable functional parallels. Genetic studies in both organisms
      have identified highly conserved pathways regulating cell movement and polarity,
      wound healing, innate immunity and appendage formation. More recently, it has
      emerged that the establishment and repair of the barrier function of the
      integument are also achieved by common mechanisms involving genes responsible
      both for cross-linking surface proteins and for assembly of cellular tight
      junctions. These studies support the model that the formation and maintenance of
      the epidermal impermeable barrier in a wide range of species relies on two
      independent and complementary pathways.

PMID- 15950459
TI  - Divergent biological effects of estradiol and diethylstilbestrol in the prostate
      cancer cell line MOP.
AB  - The involvement of mutated androgen receptors (mut-AR) in the actions of
      estrogens in prostate cancer cells is controversial. This work was designed to
      determine the role of such receptors in the growth inhibition by estradiol (E2)
      and androgens of the MOP cell line, a derivative of the LNCaP cell line.
      Diethylstilbestrol (DES) was used as a "tool". E2 like DHT and R1881 inhibits MOP
      cell proliferation while DES does not. E2 and R1881 down regulate mut-AR mRNA,
      DES does not. E2 enhances mut-AR transcriptional activity less efficiently than
      R1881 while DES does not. E2 and R1881 up regulate PSA secretion in a dose
      dependent manner, DES does it marginally at 10(-6)M. MOP cells express low
      amounts of ERalpha and ERbeta mRNA but neither DES nor E2 and R1881 do enhance ER
      transcriptional activity. DES and E2 bind to mut-AR with relative binding
      affinities which are respectively 1/175 and 1/10 that of DHT. The E2 and androgen
      repressed proliferation is prevented by DES and by the anti-androgen
      bicalutamide. In LNCaP cells, DES prevents the androgen-enhanced proliferation.
      These results strongly suggest that: (a) the putative endogenous ERs are
      biologically inactive in MOP cells, (b) the E2-repressed proliferation results
      from hormone binding to mut-AR and, (c) DES is an anti-androgen in mut-AR
      expressing cell line.

PMID- 15950460
TI  - Fast pyrolysis of soybean cake: product yields and compositions.
AB  - This study was an investigation of the role of important parameters influencing
      pyrolysis yields from soybean cake. Experiments were carried out at temperatures
      ranging from 400 to 700 degrees C, for various nitrogen flow rates, heating rates
      and particle sizes. The maximum liquid yield was 42.83% at a pyrolysis
      temperature of 550 degrees C with a sweeping gas rate of 200 cm3 min(-1) and
      heating rate of 700 degrees C min(-1) for a soybean cake sample having 0.425 <
      D(p) < 0.85 mm particle size. The various characteristics of liquid product were
      identified. Thus, the aliphatic sub-fraction of the bio-oil was analysed by GC-MS
      and further structural analyses of bio-oil and aromatic and polar sub-fractions
      were conducted using FT-IR and 1H-NMR. The H/C ratios and the structural analysis
      of the fractions obtained from the biocrudes showed that the fractions were quite
      similar to currently utilised transport fuels.

PMID- 15950461
TI  - Fixed-bed catalytic pyrolysis of cotton-seed cake: effects of pyrolysis
      temperature, natural zeolite content and sweeping gas flow rate.
AB  - Catalyzed pyrolysis of cotton-seed cake was studied under different experimental
      conditions. Variables investigated were pyrolysis temperature, zeolite content
      and sweeping gas flow rate. Experiments were carried out isothermally. Liquids,
      gases and char were obtained as products of pyrolysis. The distributions of these
      products were determined for various contents (1, 5, 10, 20 wt.% of raw material)
      of zeolite at four different pyrolysis temperatures. The maximum liquid yield
      obtained was 30.84% at a pyrolysis temperature of 550 degrees C with a sweeping
      gas flow rate of 100 cm(3) min(-1) in the presence of clinoptilolite (20% based
      on raw material) as catalyst. The pyrolytic and catalytic liquid products were
      analysed in detail to determine the predominant chemical classes and the
      identities of the major compounds present.

PMID- 15950462
TI  - Active site binding modes of curcumin in HIV-1 protease and integrase.
AB  - Structure models for the interaction of curcumin with HIV-1 integrase (IN) and
      protease (PR) were investigated using computational docking. Curcumin was found
      to bind preferentially in similar ways to the active sites of both IN and PR. For
      IN, the binding site is formed by residues Asp64, His67, Thr66, Glu92, Thr93,
      Asp116, Ser119, Asn120, and Lys159. Docked curcumin contacts the catalytic
      residues adjacent to Asp116 and Asp64, and near the divalent metal (Mg2+). In the
      PR docking, the curcumin structure fitted well to the active site, interacting
      with residues Asp25, Asp29, Asp30, Gly27', Asp29', and Asp30'. The results
      suggest that o-hydroxyl and/or keto-enol structures are important for both IN and
      PR inhibitory actions. The symmetrical structure of curcumin seems to play an
      important role for binding to the PR protein, whereas the keto-enol and only one
      side of the terminal o-hydroxyl showed tight binding to the IN active site.

PMID- 15950463
TI  - Identification of aminopiperidine benzamides as MCHr1 antagonists.
AB  - The identification of a novel series of benzamide-containing MCHr1 antagonists is
      described. Compound 22 displayed moderate efficacy in a diet induced obesity mice
      model.

PMID- 15950464
TI  - (2R)-2-methylchromane-2-carboxylic acids: discovery of selective PPARalpha
      agonists as hypolipidemic agents.
AB  - A SAR study was conducted on chromane-2-carboxylic acid toward selective
      PPARalpha agonisim. As a result, highly potent, and selective PPARalpha agonists
      were discovered. The optimized compound 43 exhibited robust lowering of total
      cholesterol levels in hamster and dog animal models.

PMID- 15950465
TI  - (1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: a novel
      class of potent MSK-1-inhibitors.
AB  - A novel series of imidazo[4,5-c]pyridines bearing a 1,2,5-oxadiazol-3-ylamine
      functionality has been developed. These are potent inhibitors of mitogen and
      stress-activated protein kinase-1.

PMID- 15950466
TI  - Synthesis and biological evaluation of quinoxaline-5,8-diones that inhibit
      vascular smooth muscle cell proliferation.
AB  - A series of 6-arylamino-2,3-bis(pyridin-2-yl)-7-chloro-quinoxaline-5,8-diones
      were synthesized and evaluated for their inhibitory activity on the rat aortic
      smooth muscle cell (RAoSMC) proliferation. The quinoxaline-5,8-diones exhibited a
      potent antiproliferative activity. Further mechanistic study revealed that the
      inhibitory effect of one representative quinoxaline-5,8-dione on SMC
      proliferation was mediated by modulation of the extracellular signal-regulated
      kinase 1/2 signaling pathway in the RAoSMCs.

PMID- 15950467
TI  - Synthesis and structure-activity relationships of biarylcarboxamide bis
      aminopyrrolidine urea derived small-molecule antagonists of the melanin
      concentrating hormone receptor-1 (MCH-R1).
AB  - A novel series of bis-aminopyrrolidine ureas containing either a 4
      biphenylcarboxmide or 5-phenyl-2-thiophenecarboxamide group have been identified
      as potent and functional antagonists of the melanin-concentrating hormone
      receptor-1. Syntheses and SAR are described, which led to the discovery of
      compounds with high binding affinity (Ki = 1 nM) for the receptor. Preliminary in
      vitro metabolic stability data are also reported for key compounds.

PMID- 15950469
TI  - Solid state photochemistry of 1,4-dihydropyridines.
AB  - Photochemical behavior of some 1,4-dihydropyridines has been investigated in the
      solid state. Whereas upon irradiation of 1,4-dihydropyridines in solution phase,
      their photo-oxidation and formation of pyridine derivatives have been observed,
      irradiation of these compounds in the solid state decreases their light
      sensitivity. In many cases photo-oxidation has been observed only in very low
      yields.

PMID- 15950468
TI  - Synthesis and biological evaluation of novel 1,4-naphthoquinone derivatives as
      antibacterial and antiviral agents.
AB  - A series of 1,4-naphthoquinone derivatives were synthesized and evaluated for
      antibacterial and antiviral activities. The structure-activity relationships of
      these compounds were also studied. The results suggest that compounds 9-22 showed
      in vitro marked antibacterial activity. Compounds 4c and 7a showed inhibitory
      effect against RNA dependent RNA polymerase induced poliovirus type 2 infected
      HeLa cells.

PMID- 15950470
TI  - Structure-activity relationship of a series of cyclohexylpiperidines bearing an
      amide side chain as antagonists of the human melanocortin-4 receptor.
AB  - A series of cyclohexylpiperazines was synthesized as potent and selective
      antagonists of the human MC4 receptor. Compound 14t displayed binding affinity
      (Ki) of 4.2 and 1100 nM at MC4R and MC3R, respectively.

PMID- 15950472
TI  - Pyrrolo[1,2-a][1,4]benzodiazepine: a novel class of non-azole anti-dermatophyte
      anti-fungal agents.
AB  - Broad screening revealed compound 1a to be a novel anti-fungal agent with high
      specificity towards dermatophytes. The anti-fungal structure-activity
      relationship of this novel class of 5,6-dihydro-4H-pyrrolo[1,2
      a][1,4]benzodiazepines is described together with its mode of action that
      appeared to be the inhibition of squalene epoxidase. Preliminary in vivo results
      of the most active compounds are also reported.

PMID- 15950471
TI  - Structure-driven HtL: design and synthesis of novel aminoindazole inhibitors of c
      Jun N-terminal kinase activity.
AB  - The design and synthesis of a new series of c-Jun N-terminal kinase inhibitors
      are reported. The novel series of substituted amino indazoles were designed based
      on a combination of hits from high-throughput screening and X-ray crystal
      structure information of the compounds crystallised into the JNK-1 ATP binding
      site.

PMID- 15950473
TI  - Neomycin improves cationic lipid-mediated transfection of DNA in human cells.
AB  - Delivery of oligonucleotides has been a major impediment in the development of
      nucleic acid based drugs. In this report, we show that neomycin, an
      aminoglycoside antibiotic, when combined with a cationic lipid preparation such
      as DOTAP, enhances transfection efficiency of both reporter plasmids and
      oligonucleotides and results in a significant increase in transgene expression.
      The results described here open a new lead in ongoing efforts for oligonucleotide
      delivery.

PMID- 15950474
TI  - Novel iron-specific fluorescent probes.
AB  - A series of novel iron-specific fluorescent probes is reported where the chelator
      function unusually forms part of the fluorescent moiety. The ability of this
      range of molecules to permeate human erythrocyte ghost membranes was
      investigated.

PMID- 15950475
TI  - Anticipatory locomotor adjustments of the trail limb during surface
      accommodation.
AB  - This paper explores anticipatory locomotor adjustments of the trail limb when
      stepping up to a new level. The kinematics and kinetics of the trail limb for
      nine subjects were compared across level gait and surface accommodation. The
      largest generation of new rotational energy was found at the trail ankle, during
      the latter part of stance (i.e. ankle 'push-off'). Accelerations of the head,
      arms and trunk (HAT) and foot segments during the same phase indicate that the
      ankle power acted to push the body and lead limb up onto the new level and drive
      the foot upwards at toe-off. The shank was more vertical at toe-off to ensure
      that the ankle energy would drive the limb upwards, rather than forward into the
      surface. The vertical hip translation energy increased over 300%, acting to pull
      upwards on the hip to increase trail limb elevation. The increased hip
      translational energy could be due to extension of the lead limb after it was
      placed on the surface and/or the piston-like drive of the increased rotational
      energy at the trail ankle during late stance. The findings add to the knowledge
      of whole body coordination strategies during anticipatory locomotor adjustments
      when the entire body is raised to a new level.

PMID- 15950476
TI  - Viral stop-and-go along microtubules: taking a ride with dynein and kinesins.
AB  - Incoming viral particles move from the cell surface to sites of viral
      transcription and replication. By contrast, during assembly and egress, subviral
      nucleoprotein complexes and virions travel back to the plasma membrane. Because
      diffusion of large molecules is severely restricted in the cytoplasm, viruses use
      ATP-hydrolyzing molecular motors of the host for propelling along the
      microtubules, which are the intracellular highways. Recent studies have revealed
      that, besides travelling inside endocytic or exocytic vesicles, viral proteins
      interact directly with dynein or kinesin motors. Understanding the molecular
      mechanisms of cytoplasmic viral transport will aid in the construction of viral
      vectors for human gene therapy and the search for new antiviral targets.

PMID- 15950477
TI  - Eukaryotic transcription factors as direct nutrient sensors.
AB  - The recognition of changes in environmental conditions, and the ability to adapt
      to these changes, is essential for the viability of cells. There are numerous
      well-characterized systems by which the presence or absence of an individual
      metabolite can be recognized by a cell. The recognition of a metabolite is,
      however, just one step of a process that often results in changes in the
      expression of sets of genes required to respond to that metabolite. The
      signalling pathway between metabolite recognition and transcriptional control is
      often complex. However, recent evidence from yeast suggests that complex
      signalling pathways might be circumvented via the direct interaction between
      individual metabolites and regulators of RNA polymerase II transcription.

PMID- 15950478
TI  - Genistein derivatives as selective estrogen receptor modulators: sonochemical
      synthesis and in vivo anti-osteoporotic action.
AB  - Genistein derivatives were synthesized from genistein through a facile
      sonochemical approach in high yields. The bioassay was performed on
      ovariectomized (OVX) rats in terms of bone mineral density (BMD) and the weight
      of bone ash (WBA) to lead to the discovery of eight novel genistein-based
      selective estrogen receptor modulators. Attention to the structure-activity
      relationship disclosed that the newly introduced 2-hydroxyethylthio scaffolds
      were essential for the anti-osteoporotic activity. Moreover, the anti
      osteoporotic action of genistein, deprivable by methylation, could be restored
      and enhanced by subsequent sulfonation. The most promising compound was 4',5,7
      tri[3-(2-hydroxyethylthio)propoxy]isoflavone, displaying 24% (or 8%) increment in
      BMD and 31% (or 11%) increase in WBA of the femora relative to those discerned
      with the OVX (or genistein) group. Acute toxicity test showed that none of the
      active compounds was acutely toxic.

PMID- 15950479
TI  - The transport mechanisms of (222)Rn in soil at Tateishi as an anomaly spot in
      Japan.
AB  - The (222)Rn concentration profiles in soil have been measured at an anomaly spot
      in Tateishi, Japan. In winter, the concentrations were low and showed a negative
      gradient with depth, but in other seasons, the concentration had both positive
      and negative gradients with depth, and dramatically changed by time. On the
      assumption that there was ventilation in deep layers and with driving forces of
      wind and temperatures, these phenomena were successfully explained. This finding
      would contribute to a numerical model for (222)Rn transport in soil.

PMID- 15950480
TI  - Thermal stability of radiation-induced free radicals in gamma-irradiated L
      alanine single crystals.
AB  - Decay of the radiation-induced stable free radicals in l-alanine single crystals
      and powders at the temperatures from 379 to 476 K was examined by electron
      paramagnetic resonance. For single crystals, the calculated activation energy of
      the radical decay is 104.3+/-1.7 kJ/mol (i.e. 12 538+/-202 K) and the frequency
      factor lnv (O) is 24.1+/-0.4 min(-1). The lifetime of the radical in single
      crystals at 296 K is 162 years. The results confirm the long-term stability of
      the radicals, but the decay was found to be faster in large crystals than in
      powders.

PMID- 15950482
TI  - Double-crowned valved stents for off-pump mitral valve replacement.
AB  - OBJECTIVE: An animal model has been designed to assess the feasibility of off
      pump mitral valve replacement using valved stents. METHODS: Glutaraldehyde
      preserved homograft was sutured inside a prosthetic tube (Dacron). Then, two self
      expandable nitinol Z-stents were sutured on the external surface of the
      prosthesis in such a way to create two self-expanding crowns for fixation. In
      adult pigs and under general anesthesia, the left atrium was exposed through a
      left thoracotomy and atrio-ventricular roadmapping was performed with
      intravascular ultrasound (IVUS) and fluoroscopy. The double-crowned valved stents
      were loaded into a delivery sheath. The sheath was then introduced into the left
      atrium and the valved stents was deployed in mitral position in such a way that
      the part in between the two stents was at the level of the mitral annulus.
      Intracardiac Unltrasound (ICUS) was used to assess the valve function.
      Hemodynamic parameters were gathered as well. Animal survived for no more than 3h
      after the valve deployment and gross anatomy examination of the left heart was
      carried out. RESULTS: The mean height of the valved stents was 29.4+/-0.2 mm,
      with an internal diameter of 20.4+/-1.0mm, and an external diameter of 25.5+/-0.8
      mm. The procedure was successfully carried out in eight animals. In vivo
      evaluation showed a native mitral annulus diameter of 24.9+/-0.6 mm, and a mean
      mitral valve area of 421.4+/-17.5 mm2. ICUS showed a mild mitral regurgitation in
      three out of eight animals. Mean pressure gradient across the valved stents was
      2.6+/-3.1 mmHg. Mean pressure gradient across the left ventricular outflow tract
      (LVOT) was 6.6+/-5.2 mmHg. The mean survival time was 97.5+/-56.3 min (survival
      time range was 40-180 min). One animal died due to the occlusion of the LVOT
      because of valved stents displacement. Postmortem evaluation confirmed correct
      positioning of the valved stent in the mitral position in seven out of eight
      animals. No atrial or ventricular lesions due to the valved stents were found.
      CONCLUSIONS: Off-pump implantation of a self-expandable valved stent in the
      mitral position is technically feasible. Further studies will assess if this
      procedure is also feasible in humans.

PMID- 15950483
TI  - Thyrotropin receptor autoantibodies in Graves' disease.
AB  - Clinical thyrotoxicosis in Graves' disease patients is caused by thyrotropin
      receptor (TSHR)-stimulating autoantibodies. The molecular mechanisms of TSHR post
      translational modification, TSHR signaling and TSHR-autoantibody interaction are
      still debatable, and the precise interaction of stimulating and blocking
      autoantibodies with TSHR is unclear. Recent TSHR epitope studies indicate that
      binding sites for stimulating and blocking autoantibodies are close together, not
      on distinct or distant parts of the molecule. Furthermore, new methods to detect
      TSHR autoantibodies and their clinical use are addressed. Highly sensitive TSHR
      autoantibody assays are widely available and cost efficient, and their routine
      clinical use might help in the differential diagnosis of hyperthyroidism and
      disease outcome prediction in patients with high levels of TSHR autoantibodies.

PMID- 15950481
TI  - Regional neural activity within the substantia nigra during peri-ictal flurothyl
      generalized seizure stages.
AB  - Structures responsible for the onset, propagation, and cessation of generalized
      seizures are not known. Lesion and microinfusion studies suggest that the
      substantia nigra pars reticulata (SNR) seizure-controlling network could play a
      key role. However, the expression of neural activity within the SNR and its
      targets during discrete pre- and postictal periods has not been investigated. In
      rats, we used flurothyl to induce generalized seizures over a controlled time
      period and 2-deoxyglucose autoradiography mapping technique. Changes in neural
      activity within the SNR were region-specific. The SNRposterior was selectively
      active during the pre-clonic period and may represent an early gateway to seizure
      propagation. The SNRanterior and superior colliculus changed their activity
      during progression to tonic-clonic seizure, suggesting the involvement in
      coordinated regional activity that results in inhibitory effects on seizures. The
      postictal suppression state was correlated with changes in the SNR projection
      targets, specifically the pedunculopontine tegmental nucleus and superior
      colliculus.

PMID- 15950484
TI  - Unraveling electrical signaling strategies in hypothalamic feeding circuits.

PMID- 15950485
TI  - Estrogen stimulation of COX-2-derived PGI2 confers atheroprotection.
AB  - Although selective cyclooxygenase-2 (COX-2) inhibitors provide relief from pain
      and inflammation, they also reduce the formation of the atheroprotective
      prostaglandin I2 (PGI2). They do not reduce the formation of the COX-1-derived
      thromboxane A2 (TXA2), however, which is both atherogenic and a potent
      vasoconstrictor. For this reason, the effects of TXA2 might be exacerbated during
      extended therapy with COX-2 inhibitors, potentially predisposing patients to
      heart attack and stroke. Recent studies have demonstrated that the
      atheroprotective effects of estrogen are induced through PGI2 production, through
      COX-2 activation. This explains how estrogen production in pre-menopausal females
      is beneficial for the heart and also raises the possibility that COX-2 inhibitors
      might be particularly hazardous to females.

PMID- 15950486
TI  - Portal hypertension produces an evolutive hepato-intestinal pro- and anti
      inflammatory response in the rat.
AB  - An inflammatory etiopathogeny can be suggested in portal hypertensive enteropathy
      since infiltration of the intestinal wall by mononuclear cells has been described
      in this condition. This work was carried out with the intention of shedding light
      on this matter. Male Wistar rats were divided into 4 control groups and 4 groups
      with partial portal vein ligation at 1, 2, 3 and 15 months. TNF-alpha, IL-1beta
      and IL-10 were quantified in liver and ileum by ELISA. CO and NO were measured in
      splanchnic and systemic vein by spectrophotometry and Griess reaction,
      respectively. Expression of constitutive and inducible isoforms of NO and HO were
      assayed by Western blot in liver and ileum. An increased hepatic release of
      proinflammatory mediators (TNF-alpha, IL-1beta and NO) associated with intestinal
      release of anti-inflammatory mediators (IL-10, CO) occurs in an early evolutive
      phase (1 month) of experimental portal hypertension. On the contrary, in the long
      term (15 months), the increase in the intestinal release of proinflammatory
      mediators (TNF-alpha, IL-1beta) is associated with an increase in the hepatic
      release of anti-inflammatory mediators (IL-10, CO). These results suggest that
      experimental prehepatic portal hypertension presents changes in the serum and
      tissular (liver and small bowel) concentrations of mediators which are considered
      as pro- and anti-inflammatory.

PMID- 15950487
TI  - The study of metabolic pathways in tumors based on the transcriptome.
AB  - DNA microarray technology revolutionized gene-expression analysis in molecular
      biology to observe patterns of gene expression in genomic scale. We review the
      biological aspects of genome-wide gene-expression activity in tumors specially
      focusing on the analysis of enzyme coding genes. First, the methods for analyzing
      gene-expression data for the study of metabolome in silico are discussed showing
      SV40T antigen expressing liver tumor data as an example. Next, an application for
      tumor metabolome analysis utilizing a reference set of gene-expression profiles
      is shown.

PMID- 15950488
TI  - Retinoic acid negatively regulates GDNF and neurturin receptor expression and
      responsiveness in embryonic chicken sympathetic neurons.
AB  - Neurotrophins and members of the GDNF family influence the generation,
      differentiation and survival of sympathetic neurons during development.
      Neurotrophin receptor expression and responsiveness has previously been shown to
      be regulated by all-trans retinoic acid (RA) in embryonic chicken sympathetic
      neurons. To determine if RA also regulates responsiveness to GDNF family members
      and expression of their receptors, we studied the effect of treating cultures of
      these neurons at a stage when they survive in response to GDNF and neurturin. RA
      caused a dose-dependent decrease in the survival response to both GDNF and
      neurturin. Transcripts for the ligand-specifying receptors for GDNF and
      neurturin, GFRalpha-1 and GFRalpha-2, as well as the common signal transducing
      receptor Ret were all down-regulated by RA treatment in a dose-dependent manner.
      Transcripts for all three retinoic acid receptors RaRalpha, RaRbeta and RaRgamma
      as well as the enzymes involved in RA synthesis, Adh-1 and RALDH-2, RALDH-3, were
      present in both sympathetic targets and neurons. Studies with retinoic acid
      receptor agonists and antagonists revealed that the effects of RA on receptor
      expression were mediated mainly by RaRalpha. These findings implicate RA in
      regulating the actions of members of the GDNF family on developing sympathetic
      neurons.

PMID- 15950489
TI  - Disruption of palladin results in neural tube closure defects in mice.
AB  - Palladin is a newly identified actin-associated protein which was proposed to be
      involved in actin cytoskeleton organization and nervous system development. Here,
      we show that inactivation of palladin leads to embryonic lethality due to severe
      defects of cranial neural tube closure and herniation of liver and intestine. It
      was found that palladin(-/-) embryos died around E15.5 and developed cranial
      neural tube closure defects (NTDs) with 100% penetrance. Whole mount in situ
      hybridization revealed that expression of palladin in early wild type embryos
      (E8.5) was specifically restricted in the elevating cranial neural folds where
      the neural tube closure is initiated. Palladin expression closely mirrors the
      phenotypic defects observed in palladin(-/-) mutants. While in E 9.5 and E10.5
      embryos palladin was ubiquitously expressed. In vitro study revealed that
      formation of stress fibers in cytoplasm, cell adherent ability to extra-cellular
      matrix protein fibronectin and cell migration were dramatically disturbed in
      palladin(-/-) murine embryonic fibroblast cells (MEFs). Our findings suggest that
      palladin plays important roles in actin stress fiber formation, cell adhesion and
      migration. We propose that palladin is required for the initiation of neural tube
      closure and provides an important new candidate that may be implicated in the
      etiology of human NTDs.

PMID- 15950490
TI  - Recent advances on the complement system of teleost fish.
AB  - The complement system plays an essential role in alerting the host of the
      presence of potential pathogens, as well as in their clearing. In addition,
      activation of the complement system contributes significantly in the
      orchestration and development of an acquired immune response. Although the
      complement system has been studied extensively in mammals, considerably less is
      known about complement in lower vertebrates, in particular teleost fish. Here we
      review our current understanding of the role of fish complement in phagocytosis,
      respiratory burst, chemotaxis and cell lysis. We also thoroughly review the
      specific complement components characterized thus far in various teleost fish
      species. In addition, we provide a comprehensive compilation on complement host
      pathogen interactions, in which we analyze the role of fish complement in host
      defense against bacteria, viruses, fungi and parasites. From a more physiological
      perspective, we evaluate the knowledge accumulated on the influence of stress,
      nutrition and environmental factors on levels of complement activity and
      components, and how the use of this knowledge can benefit the aquaculture
      industry. Finally, we propose future directions that are likely to advance our
      understanding of the molecular evolution, structure and function of complement
      proteins in teleosts. Such studies will be pivotal in providing new insights into
      complement-related mechanisms of recognition and defense that are essential to
      maintaining fish homeostasis.

PMID- 15950491
TI  - Innate immunity of fish (overview).
AB  - The innate immune system is the only defence weapon of invertebrates and a
      fundamental defence mechanism of fish. The innate system also plays an
      instructive role in the acquired immune response and homeostasis and is therefore
      equally important in higher vertebrates. The innate system's recognition of non
      self and danger signals is served by a limited number of germ-line encoded
      pattern recognition receptors/proteins, which recognise pathogen associated
      molecular patterns like bacterial and fungal glycoproteins and
      lipopolysaccharides and intracellular components released through injury or
      infection. The innate immune system is divided into physical barriers, cellular
      and humoral components. Humoral parameters include growth inhibitors, various
      lytic enzymes and components of the complement pathways, agglutinins and
      precipitins (opsonins, primarily lectins), natural antibodies, cytokines,
      chemokines and antibacterial peptides. Several external and internal factors can
      influence the activity of innate immune parameters. Temperature changes, handling
      and crowding stress can have suppressive effects on innate parameters, whereas
      several food additives and immunostimulants can enhance different innate factors.
      There is limited data available about the ontogenic development of the innate
      immunological system in fish. Active phagocytes, complement components and enzyme
      activity, like lysozyme and cathepsins, are present early in the development,
      before or soon after hatching.

PMID- 15950492
TI  - Modulation of behavior and cortical motor activity in healthy subjects by a
      chronic administration of a serotonin enhancer.
AB  - SSRIs are postulated to modulate motor behavior. A single dose of selective
      serotoninergic reuptake inhibitors (SSRIs) like fluoxetine, paroxetine, or
      fluvoxamine, has been shown to improve motor performance and efficiency of
      information processing for simple sensorimotor tasks in healthy subjects. At a
      cortical level, a single dose of SSRI was shown to induce a hyperactivation of
      the primary sensorimotor cortex (S1M1) involved in the movement (Loubinoux, I.,
      Boulanouar, K., Ranjeva, J. P., Carel, C., Berry, I., Rascol, O., Celsis, P., and
      Chollet, F., 1999. Cerebral functional magnetic resonance imaging activation
      modulated by a single dose of the monoamine neurotransmission enhancers
      fluoxetine and fenozolone during hand sensorimotor tasks. J. Cereb. Blood Flow
      Metab. 19 1365--1375, Loubinoux, I., Pariente, J., Boulanouar, K., Carel, C.,
      Manelfe, C., Rascol, O., Celsis, P., and Chollet, F., 2002. A Single Dose of
      Serotonin Neurotransmission Agonist Paroxetine Enhances Motor Output. A double
      blind, placebo-controlled, fMRI study in healthy subjects. NeuroImage 15 26--36).
      Since SSRIs are usually given for several weeks, we assessed the behavioral and
      cerebral effects of a one-month chronic administration of paroxetine on a larger
      group. In a double-blind, placebo controlled and crossover study, 19 subjects
      received daily 20 mg paroxetine or placebo, respectively, over a period of 30
      days separated by a wash-out period of 3 months. After each period, the subjects
      underwent an fMRI (active or passive movement, dexterity task, sensory
      discrimination task) and a behavioral evaluation. Concurrently, a TMS
      (transcranial magnetic stimulation) study was conducted (Gerdelat-Mas, A.,
      Loubinoux, I., Tombari, D., Rascol, O., Chollet, F., Simonetta-Moreau, M., 2005.
      Chronic administration of selective serotonin re-uptake inhibitor (SSRI)
      paroxetine modulates human motor cortex excitability in healthy subjects.
      NeuroImage 27,314--322). RESULTS: On the one hand, paroxetine improved motor
      performances at the finger tapping test (P=0.02) without affecting choice
      reaction time, strength and dexterity significantly. Subjects were also faster in
      processing the spatial incongruency between a stimulus and the motor response
      (P=0.04). In order to differentiate behavioral components, a principal component
      analysis was performed on all motor tests, and several characteristics were
      differentiated: strength, speed, skill, attention, and motor response coding.
      Paroxetine would improve the efficiency of motor response coding (MANOVA on the
      factors; factor 3, P=0.01). On the other hand, the chronic administration induced
      a significant hypoactivation of S1M1 whatever the task: motor or sensory, simple
      or complex (random effect analysis, P<0.05). The hypoactivation correlated with
      the improvement of performances at the finger tapping test (P<0.05) suggesting
      more efficiency in cerebral motor processing. CONCLUSIONS: Our results showed a
      clear modulation of sensory and motor cerebral activation after a chronic
      paroxetine administration. An improvement in both behavior and cerebral
      efficiency was suggested. It could be hypothesized that monoamines, by an
      unspecific effect, may tune the response of pyramidal neurons to optimize
      performances.

PMID- 15950493
TI  - A complete species-level phylogeny of the Hylobatidae based on mitochondrial ND3
      ND4 gene sequences.
AB  - The Hylobatidae (gibbons) are among the most endangered primates and their
      evolutionary history and systematics remain largely unresolved. We have
      investigated the species-level phylogenetic relationships among hylobatids using
      1257 bases representing all species and an expanded data set of up to 2243 bases
      for select species from the mitochondrial ND3-ND4 region. Sequences were obtained
      from 34 individuals originating from all 12 recognized extant gibbon species.
      These data strongly support each of the four previously recognized clades or
      genera of gibbons, Nomascus, Bunopithecus, Symphalangus, and Hylobates, as
      monophyletic groups. Among these clades, there is some support for either
      Bunopithecus or Nomascus as the most basal, while in all analyses Hylobates
      appears to be the most recently derived. Within Nomascus, Nomascus sp. cf.
      nasutus is the most basal, followed by N. concolor, and then a clade of N.
      leucogenys and N. gabriellae. Within Hylobates, H. pileatus is the most basal,
      while H. moloch and H. klossii clearly, and H. agilis and H. muelleri likely form
      two more derived monophyletic clades. The segregation of H. klossii from other
      Hylobates species is not supported by this study. The present data are (1)
      consistent with the division of Hylobatidae into four distinct clades, (2)
      provide the first genetic evidence for all the species relationships within
      Nomascus, and (3) call for a revision of the current relationships among the
      species within Hylobates. We propose a phylogenetic tree as a working hypothesis
      against which intergeneric and interspecific relationships can be tested with
      additional genetic, morphological, and behavioral data.

PMID- 15950494
TI  - HERG-Lite: a novel comprehensive high-throughput screen for drug-induced hERG
      risk.
AB  - INTRODUCTION: Direct block of I(Kr) by non-antiarrhythmic drugs (NARDs) is a
      major cause of QT prolongation and torsades de pointes (TdP), and has made the
      hERG potassium channel a major target of drug safety programs in cardiotoxicity.
      Block of hERG currents is not the only way that drugs can adversely impact the
      repolarizing current I(Kr), however. We have shown recently that two drugs in
      clinical use do not block hERG but produce long QT syndrome (LQTS) and TdP by
      inhibiting trafficking of hERG to the cell surface. To address the need for an
      inexpensive, rapid, and comprehensive assay to predict both types of hERG risk
      early in the drug development process, we have developed a novel antibody-based
      chemiluminescent assay called HERG-Lite. METHODS: HERG-Lite monitors the
      expression of hERG at the cell surface in two different stable mammalian cell
      lines. One cell line acts as a biosensor for drugs that inhibit hERG trafficking,
      while the other predicts hERG blockers based on their ability to act as
      pharmacological chaperones. In this study, we have validated the HERG-Lite assay
      using a panel of 100 drugs: 50 hERG blockers and 50 nonblockers. RESULTS: HERG
      Lite correctly predicted hERG risk for all 100 test compounds with no false
      positives or negatives. All 50 hERG blockers were detected as drugs with hERG
      risk in the HERG-Lite assay, and fell into two classes: B (for blocker) and C
      (for complex; block and trafficking inhibition). DISCUSSION: HERG-Lite is the
      most comprehensive assay available for predicting drug-induced hERG risk. It
      accurately predicts both channel blockers and trafficking inhibitors in a rapid,
      cost-effective manner and is a valuable non-clinical assay for drug safety
      testing.

PMID- 15950495
TI  - Development of a surgical approach for telemetering guinea pigs as a model for
      screening QT interval effects.
AB  - INTRODUCTION: Identifying a compound's risk of potentially producing Torsade de
      Pointes (TdP)/QT interval prolongation has become a goal early within the drug
      development process. Our aim was to develop a surgical approach for instrumenting
      guinea pigs for collecting ECG data. METHODS: Male Dunkin Hartley guinea pigs
      (386-661 g) were surgically implanted with telemetry transducers for the
      measurement of lead II ECG and arterial blood pressure. Using strict aseptic
      techniques and isofluorane anaesthesia (0.5-5.0%), one of the three implantation
      procedures was used. In Phase I the animals were either implanted
      intraperitoneally (abdominal aorta cannulated) or subcutaneously (carotid artery
      cannulated). In Phase II all animals were implanted subcutaneously and the
      subcutaneous pocket formed either with a single incision, as in Phase I, or a
      double incision. RESULTS: Phase I-During intraperitoneal implantation, rupture of
      the aorta occurred in 50% of the animals. The remaining animals were terminated
      between 2 and 14 days postsurgery on human grounds. All of the animals implanted
      subcutaneously survived the surgical procedure and the following 28 days. Skin
      thinning over the implant occurred in 25% of the animals in weeks 5-6. Phase II
      Following single incision subcutaneous implantation 72% of the animals were
      terminated within the 28-day postsurgery due to skin rupture over the implant
      body, with only 22% of the animals viable after 28 days. Following double
      incision subcutaneous implantation 86% of animals were viable after 28 days and
      thus the recommended method for implantation. DISCUSSION: The improvements to the
      surgical approach have improved survival rates and increased the potential for
      robust, long term use of telemetered guinea pig colonies for screening for QT
      prolonging potential and additional cardiovascular assessment in vivo.

PMID- 15950496
TI  - Comparison of the chondrosarcoma cell line SW1353 with primary human adult
      articular chondrocytes with regard to their gene expression profile and
      reactivity to IL-1beta.
AB  - OBJECTIVE: In this study, the human chondrosarcoma cell line SW1353 was
      investigated by gene expression analysis in order to validate it as an in vitro
      model for primary human (adult articular) chondrocytes (PHCs). METHODS: PHCs and
      SW1353 cells were cultured as high density monolayer cultures with and without
      1ng/ml interleukin-1beta (IL-1beta). RNA was isolated and assayed using a custom
      made oligonucleotide microarray representing 312 chondrocyte-relevant genes. The
      expression levels of selected genes were confirmed by real-time polymerase chain
      reaction and the gene expression profiles of the two cell types, both with and
      without IL-1beta treatment, were compared. RESULTS: Overall, gene expression
      profiling showed only very limited similarities between SW1353 cells and PHCs at
      the transcriptional level. Similarities were predominantly seen with respect to
      catabolic effects after IL-1beta treatment. In both cell systems matrix
      metalloproteinase-1 (MMP-1), MMP-3 and MMP-13 were strongly induced by IL-1beta,
      without significant induction of MMP-2. IL-6 was also found to be up-regulated by
      IL-1beta in both cellular models. On the other hand, intercellular mediators such
      as leukemia inhibitory factor (LIF) and bone morphogenetic protein-2 (BMP-2) were
      not induced by IL-1beta in SW1353 cells, but significantly up-regulated in PHCs.
      Bioinformatical analysis identified nuclear factor kappa-B (NFkappaB) as a common
      transcriptional regulator of IL-1beta induced genes in both SW1353 cells and
      PHCs, whereas other transcription factors were only found to be relevant for
      individual cell systems. CONCLUSION: Our data characterize SW1353 cells as a cell
      line with only a very limited potential to mimic PHCs, though SW1353 cells can be
      of value to study the induction of protease expression within cells, a phenomenon
      also seen in chondrocytes.

PMID- 15950497
TI  - Comparative effects of IL-1beta and hydrogen peroxide (H2O2) on catabolic and
      anabolic gene expression in juvenile bovine chondrocytes.
AB  - OBJECTIVE: To compare the effects of hydrogen peroxide (H(2)O(2)) to those of
      interleukin-1beta (IL-1beta) on gene expression in juvenile bovine articular
      chondrocytes (BAC). The study analyses the activation of nuclear factor-kappa B
      (NF-kappaB) and activator protein-1 (AP-1) transcription factors, and the mRNA
      steady-state levels of the type II collagen, aggrecan core protein matrix,
      metalloproteinases (MMP-1, -3), and transforming growth factor-beta1 (TGF-beta1)
      genes. METHODS: Confluent BAC cultures were treated for 3 and 24h with IL-1beta
      and/or different concentrations of H(2)O(2) (Protocol 1). Following initial
      treatment, a part of the cells was further subjected to another 24h with medium,
      in the presence of IL-1beta, to determine the effect of the cytokine on H(2)O(2)
      pre-treated cells (Protocol 2). Total RNA and nuclear protein extractions were
      performed to study mRNA steady-state levels (real-time polymerase chain reaction)
      and AP-1/NF-kappaB DNA binding (Electrophoretic Mobility Shift Assays),
      respectively. RESULTS: IL-1beta enhanced both AP-1 and NF-kappaB binding, whereas
      H(2)O(2) only activated AP-1. H(2)O(2) pre-treatment decreased the IL-1beta
      activation of NF-kappaB. Both H(2)O(2) and IL-1beta down-regulated type II
      collagen and aggrecan expression and increased that of MMP-1 and -3. When cells
      were pre-treated with H(2)O(2), followed by IL-1beta, the effects were the same
      as those observed with H(2)O(2) alone. However, although H(2)O(2) and IL-1beta
      were capable of increasing TGF-beta1 expression separately, subsequent incubation
      with both factors led to a partial or total abolition of TGF-beta1 up-regulation.
      CONCLUSION: The different regulation of NF-kappaB and AP-1 by H(2)O(2) and IL
      1beta underlines the distinct roles played by the two transcription factors in
      the regulation of gene expression. H(2)O(2) and IL-1beta exert similar effects on
      matrix, MMPs and TGF-beta1 gene expression. However, the association of H(2)O(2)
      and IL-1beta does not cause synergic effect, and rather leads, in some cases, to
      an opposite effect. These data provide further insights into the respective roles
      of reactive oxygen species and cytokine in the pathophysiology of joint diseases.

PMID- 15950499
TI  - Human erythrocyte delta-aminolevulinate dehydratase inhibition by monosaccharides
      is not mediated by oxidation of enzyme sulfhydryl groups.
AB  - The heme pathway enzyme delta-aminolevulinate dehydratase is a good marker for
      oxidative stress and metal intoxication. This sulfhydryl enzyme is inhibited in
      such oxidative pathologies as lead, mercury and aluminum intoxication, exposure
      to selenium organic species and diabetes. Oxidative stress is a complicating
      factor in diabetes, inducing non-enzymatic glucose-mediated reactions that change
      protein structures and impair enzyme functions. We have studied the effects of
      high glucose, fructose and ribose concentrations on delta-ALA-D activity in
      vitro. These reducing sugars inhibited delta-ALA-D with efficacies in the order
      fructose=ribose>glucose. The possible mechanism of glucose inhibition was
      investigated using lysine, DTT, and t-butylamine. Oxidation of the enzyme's
      critical sulfhydryl groups was not involved because DTT had no effect. We
      concluded that high concentrations of reducing sugars or their autoxidation
      products inhibit delta-ALA-D by a mechanism not related to thiol oxidation. Also,
      we are not able to demonstrate that the formation of a Schiff base with the
      critical lysine residue of the enzyme is involved in the inhibition of delta-ALA
      D by hexoses.

PMID- 15950498
TI  - In vitro hematopoietic differentiation of human embryonic stem cells induced by
      co-culture with human bone marrow stromal cells and low dose cytokines.
AB  - Human embryonic stem (hES) cells randomly differentiate into multiple cell types
      during embryoid body (EB) development and limited studies have focused on
      directed hematopoietic differentiation. Here, we report that the treatment of hES
      cells during EBs development with a combination of low dose hematopoietic
      cytokines, including stem cell factor (SCF), Flt-3 ligand, vascular endothelial
      growth factor (VEGF) and human bone marrow stromal cells (hBMSCs), generated cell
      clusters that contained 8.81% KDR-positive hemangioblasts, 9.94% CD34-positive
      hematopoietic stem cells and 25.7% CD45-positive mature hematopoietic cells, and
      expressed hematopoietic genes such as KDR, stem cell leukemia (scl) and runt
      related transcription factor 1 (Runx1). We provide the first evidence for the
      role of the cytokine-hBMSCs combination in promoting hematopoietic
      differentiation of hES cells, and thus provide the potential for generation of
      hematopoietic cells, as well as for understanding early developmental events that
      govern the initiation of hematopoiesis in humans.

PMID- 15950500
TI  - Establishment and characterization of endothelial cell lines from the aorta of
      miniature pig for the study of xenotransplantation.
AB  - Pig endothelial cells are the first cells to interact with human immune
      components after organ xenotransplantation, which is a procedure currently
      considered to be the best treatment option for end-stage organ failure. It is,
      therefore, essential to study the mechanisms of molecular interaction between pig
      endothelial cells and human immune components, in order to overcome xenograft
      rejection. The aim of this study was to establish immortalized pig aortic
      endothelial cell lines, in order to facilitate future in vitro studies of human
      anti-pig immune responses. Endothelial cell lines were established following the
      transfection of primary endothelial cells isolated from the aortas of the
      Minnesota miniature pig with plasmid pRNS-1 carrying genes for neomycin
      resistance and the SV40 large T antigen. The immortalized cell lines showed a
      relatively rapid doubling time (17.6h) and the endothelial cell phenotype, as
      indicated by the formation of typical cobblestone monolayers and by the
      constitutive expression of PECAM-1 and the von Willebrand factor. Flow cytometric
      analysis demonstrated the constitutive expression of SLA class I and CD86,
      whereas the expression of E-selectin and SLA class II was only induced after
      stimulation with human TNF-alpha and pig IFN-gamma, respectively. On the other
      hand, no CD80 expression was detected in the primary cells or cell lines in the
      presence or absence of either human TNF-alpha or pig IFN-gamma. A vigorous human
      T cell proliferation against these cell lines was observed in the mixed
      lymphocyte-endothelial cell culture. These results suggest that pig endothelial
      cells, immortalized by the introduction of SV40 T, retain their original
      characteristics, except for the acquired property of immortalization, and that
      they may be useful for future in vitro studies of xenogeneic human anti-pig
      immune responses.

PMID- 15950501
TI  - Acetylcholine release in hippocampus and striatum during testing on a rewarded
      spontaneous alternation task.
AB  - The present experiment tested male Sprague-Dawley rats for spontaneous
      alternation performance in a food-rewarded Y-shaped maze. Microdialysis samples,
      later assessed for acetylcholine concentration, were collected from the
      hippocampus and striatum of each rat prior to and during testing; testing
      sessions lasted 20 min. Early in testing, rats alternated at a rate of 72%.
      Alternation scores increased throughout the 20-min testing session and reached
      93% during the last 5 min. The behavioral findings suggest that, during testing,
      rats changed the basis for their performance from a spatial working memory
      strategy to a persistent turning strategy. ACh release in both hippocampus and
      striatum increased at the onset of testing. Increases in ACh release in the
      striatum began at 18% above baseline during the first 5 min of testing and
      steadily increased reaching 58% above baseline during the final 5 min. The
      progressive rise of striatum ACh release during testing occurred at about the
      time rats adopted a persistent turning strategy. In contrast, ACh release in the
      hippocampus increased by 50% with the onset of testing and remained at this level
      until declining slightly during the last 5 min of testing. The relative changes
      in ACh release in the striatum and hippocampus resulted in a close negative
      relationship between the ratio of ACh release in the hippocampus/striatum and
      alternation scores.

PMID- 15950502
TI  - Sequential femorodistal composite bypass with second generation glutaraldehyde
      stabilized human umbilical vein (HUV).
AB  - OBJECTIVE: To evaluate the performance of sequential composite bypasses with
      second generation glutaraldehyde stabilized human umbilical vein (HUV) and
      autologous vein. DESIGN: Retrospective study of consecutive patients, in a single
      centre. PATIENTS: From January 1998 to December 2003, 54 femoro-distal HUV
      autologous vein sequential composite bypasses were constructed in 52 patients
      with critical leg ischemia and absence of sufficient length of autologous vein.
      METHODS: All infra-inguinal bypass operations were registered in a computerized
      database and prospectively followed. Bypasses using sequential HUV-composite
      technique were reviewed for graft patency, limb salvage and patient survival.
      RESULTS: Primary patency and secondary patency rates at 1, 2, 3 and 4 years were
      71, 61, 53 and 53% and 89, 80, 73 and 67%, respectively. Corresponding limb
      salvage rates were 96, 92, 88 and 88%. Patient survival was 56% at 4 years. After
      30 days additional procedures to maintain graft patency were necessary in six
      bypasses. Asymptomatic occlusion of one sequential anastomosis was found in five
      patients. CONCLUSION: Graft patency and limb salvage rate support the use of the
      sequential composite technique with second generation HUV in femorodistal bypass
      surgery, when autologous vein of sufficient length is not available.

PMID- 15950503
TI  - Evaluation of a commercially available human serum amyloid A (SAA) turbidometric
      immunoassay for determination of equine SAA concentrations.
AB  - The aim of the present study was to evaluate whether equine serum amyloid A (SAA)
      concentrations could be measured reliably with a turbidometric immunoassay (TIA)
      developed for use with human serum. Intra- and inter-assay imprecision were
      evaluated by multiple measurements on equine serum pools. Assay inaccuracy was
      determined by linearity under dilution. The assay was subsequently used for
      measuring SAA concentrations in clinically healthy horses, horses with
      inflammatory diseases, horses with non-inflammatory diseases, and in horses
      before and after castration. In pools with low, intermediate and high SAA
      concentrations, the intra-assay imprecisions were 24.4%, 1.6% and 2.1%, and the
      inter-assay imprecisions were 33.2%, 4.6% and 6.5%. Slight signs of inaccuracy
      were observed, but these inaccuracies were negligible when considering the large
      dynamic range of the SAA response. The assay was able to detect the expected
      difference in SAA levels in different groups of horses. It was also able to
      demonstrate the expected dynamic changes in SAA after castration. In conclusion,
      equine SAA concentrations can be measured reliably using the TIA designed for
      human SAA.

PMID- 15950504
TI  - The equine immune response to Streptococcus equi subspecies zooepidemicus during
      uterine infection.
AB  - The purpose of this study was to describe strain-specific immune responses to
      Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) during uterine
      infection in horses. Five isolates of S. zooepidemicus were differentiated into
      four strains antigenically by bactericidal testing in blood of 12 horses, and
      genetically by pulsed-field gel electrophoresis. Eight healthy mares were then
      divided into two groups, each inoculated with one strain intrauterinely on three
      successive oestrous cycles followed by a second strain for three successive
      cycles, first and second strains being reversed for each group. Immune responses
      to both strains were assessed by bactericidal testing and immunoblotting over
      eight cycles. Both techniques indicated that immune responses to each strain
      arose at different times. Immunoblots showed greater binding to the first
      inoculated strain than to the second (P < 0.05). These data confirm that immune
      responses to S. zooepidemicus during uterine infection are partly strain
      specific.

PMID- 15950505
TI  - Recent changes in Salmonella nomenclature: the need for clarification.

PMID- 15950506
TI  - Accurate prediction of scorpion toxin functional properties from primary
      structures.
AB  - Scorpion toxins are common experimental tools for studies of biochemical and
      pharmacological properties of ion channels. The number of functionally annotated
      scorpion toxins is steadily growing, but the number of identified toxin sequences
      is increasing at much faster pace. With an estimated 100,000 different variants,
      bioinformatic analysis of scorpion toxins is becoming a necessary tool for their
      systematic functional analysis. Here, we report a bioinformatics-driven system
      involving scorpion toxin structural classification, functional annotation,
      database technology, sequence comparison, nearest neighbour analysis, and
      decision rules which produces highly accurate predictions of scorpion toxin
      functional properties.

PMID- 15950507
TI  - Similarities among receptor pockets and among compounds: analysis and application
      to in silico ligand screening.
AB  - We developed a new method to evaluate the distances and similarities between
      receptor pockets or chemical compounds based on a multi-receptor versus multi
      ligand docking affinity matrix. The receptors were classified by a cluster
      analysis based on calculations of the distance between receptor pockets. A set of
      low homologous receptors that bind a similar compound could be classified into
      one cluster. Based on this line of reasoning, we proposed a new in silico
      screening method. According to this method, compounds in a database were docked
      to multiple targets. The new docking score was a slightly modified version of the
      multiple active site correction (MASC) score. Receptors that were at a set
      distance from the target receptor were not included in the analysis, and the
      modified MASC scores were calculated for the selected receptors. The choice of
      the receptors is important to achieve a good screening result, and our clustering
      of receptors is useful to this purpose. This method was applied to the analysis
      of a set of 132 receptors and 132 compounds, and the results demonstrated that
      this method achieves a high hit ratio, as compared to that of a uniform sampling,
      using a receptor-ligand docking program, Sievgene, which was newly developed with
      a good docking performance yielding 50.8% of the reconstructed complexes at a
      distance of less than 2 A RMSD.

PMID- 15950508
TI  - 3D-QSAR comparative molecular field analysis on delta opioid receptor agonist
      SNC80 and its analogs.
AB  - Three-dimensional quantitative structure-activity relationship (3D-QSAR) models
      were constructed using comparative molecular field analysis (CoMFA) for a series
      of delta opioid receptor agonists: SNC80 analogs. Quantum chemical calculations
      on SNC80 show that protonation is preferred at the basic N4 atom over the
      alternative N1 atom, accordingly N4 protonation may contribute significantly to
      ligand-receptor interactions under physiologically relevant conditions.
      Statistically significant and predictive CoMFA models were achieved by pooling
      biological data from independent published sources, including compounds with both
      alphaR and alphaS benzylic configurations. Improved CoMFA models were obtained
      when the compounds were considered as N4-protonated species rather than neutral
      compounds. The influence of various atomic partial-charge formalisms, alignment
      schemes and additional molecular descriptors was evaluated in order to produce
      the highest quality models. In addition, separate CoMFA models were generated for
      compounds with only the alphaR benzylic configuration. These CoMFA models showed
      excellent internal predictability and consistency, and external validation using
      test-set compounds yielded predicted pIC50 values within 1log unit of the
      corresponding experimentally measured values. Key insights into the structure
      activity relationship derived from the CoMFA analysis concur with experimentally
      observed data, thus the CoMFA models presented here find utility for predicting
      the binding affinity, and guiding the design, of novel SNC80 analogs and related
      delta opioid receptor agonists.

PMID- 15950509
TI  - No association between Angiotensin Converting Enzyme (ACE) gene variation and
      endurance athlete status in Kenyans.
AB  - East African runners are continually successful in international distance
      running. The extent to which genetic factors influence this phenomenon is
      unknown. The insertion (I) rather than deletion (D) of a 287 bp fragment in the
      human angiotensin converting enzyme (ACE) gene is associated with lower
      circulating and tissue ACE activity and with endurance performance amongst
      Caucasians. To assess the association between ACE gene variation and elite
      endurance athlete status in an African population successful in distance running,
      DNA samples were obtained from 221 national Kenyan athletes (N), 70 international
      Kenyan athletes (I), and 85 members of the general Kenyan population (C). Blood
      samples were obtained from C and assayed for circulating ACE activity. ACE I/D
      (rs????--from NCBI SNPdb first time poly mentioned) genotype was determined, as
      was genotype at A22982GD (rs????--from NCBI SNPdb first time poly mentioned)
      which has been shown to associate more closely with ACE levels in African
      subjects than the I/D polymorphism. ACE I/D and A22982G genotypes explained 13
      and 24% of variation in circulating ACE activity levels (P = 0.034 and <0.001
      respectively). I/D genotype was not associated with elite endurance athlete
      status (df = 4, chi(2) = 4.1, P=0.39). In addition, genotype at 22982 was not
      associated with elite endurance athlete status (df = 4, chi(2) = 5.7, P = 0.23).
      Nor was the A allele at 22982, which is associated with lower ACE activity, more
      prevalent in N (0.52) or I (0.41) relative to C (0.53). We conclude that ACE I/D
      and A22982G polymorphisms are not strongly associated with elite endurance
      athlete status amongst Kenyans.

PMID- 15950510
TI  - Metabolic adjustments in two Amazonian cichlids exposed to hypoxia and anoxia.
AB  - The effects of graded hypoxia on the physiological and biochemical responses were
      examined in two closely related species of cichlids of the Amazon: Astronotus
      crassipinnis and Symphysodon aequifasciatus. Ten fish of each species were
      exposed to graded hypoxia for 8 h in seven oxygen concentrations (5.92, 3.15,
      1.54, 0.79, 0.60, 0.34, and 0.06 mg O(2) L(-)(1)), with the aim to evaluate
      hypoxia tolerance and metabolic adjustments, where plasma glucose and lactate
      levels, hepatic and muscle glycogen contents, and maximum enzyme activities (PK,
      LDH, MDH and CS) in skeletal and cardiac muscles were measured. Another
      experimental set was done to quantify oxygen consumption (MO(2)) and opercular
      movements in two oxygen concentrations. Hypoxia tolerance differed between the
      two species. Astronotus crassipinnis was able to tolerate anoxia for 178 min
      while S. aequifasciatus was able to withstand 222 min exposure in deep hypoxia
      (0.75 mg O(2) L(-)(1)). Suppressed MO(2) was observed during exposure to 0.34 (A.
      crassipinnis) and 0.79 mg O(2) L(-)(1) (S. aequifasciatus), while opercular
      movements increased in both species exposed to hypoxia. Higher levels of muscle
      and liver glycogen and larger hypoxia-induced increases in plasma glucose and
      lactate were observed in A. crassipinnis, which showed a higher degree of hypoxia
      tolerance. Changes in enzyme levels were tissue-specific and differed between
      species suggesting differential abilities in down-regulating oxidative pathways
      and increasing anaerobic metabolism. Based on the present data, we conclude that
      these animals are good anaerobes and highly adapted to their environment, which
      is allowed by their abilities to regulate metabolic pathways and adjust their
      enzyme levels.

PMID- 15950511
TI  - Cloning, expression and characterization of theta-class glutathione S-transferase
      from the silkworm, Bombyx mori.
AB  - This study focused on glutathione S-transferase (GST), one of the detoxification
      enzymes, from the silkworm, Bombyx mori (GSTT1). A cDNA encoding a putative GST
      was amplified by reverse transcriptase-polymerase chain reaction and sequenced.
      The deduced amino acid sequence revealed 59%, 57% and 56% identities to theta
      class GSTs of Musca domestica, Anopheles gambiae and Drosophila melanogaster,
      respectively. GSTT1 was also estimated to be close to those GSTs in a
      phylogenetic tree. Recombinant GST (rGSTT1) was functionally overexpressed in
      Escherichia coli in a soluble form, purified to homogeneity, and characterized.
      The pH-optimum of rGSTT1 was broad from pH 4 to 9 and rGSTT1 retained more than
      75% of its original activity after incubation at pH 5-11. Incubation for 30 min
      at temperatures below 50 degrees C also affected the activity insignificantly.
      The Michaelis constant for 1-chloro-2,4-dinitrobenzene was 0.48 mM.

PMID- 15950513
TI  - An integrated tool for the diagnosis of voice disorders.
AB  - A PC-based integrated aid tool has been developed for the analysis and screening
      of pathological voices. With it the user can simultaneously record speech,
      electroglottographic (EGG), and videoendoscopic signals, and synchronously edit
      them to select the most significant segments. These multimedia data are stored on
      a relational database, together with a patient's personal information, anamnesis,
      diagnosis, visits, explorations and any other comment the specialist may wish to
      include. The speech and EGG waveforms are analysed by means of temporal
      representations and the quantitative measurements of parameters such as
      spectrograms, frequency and amplitude perturbation measurements, harmonic energy,
      noise, etc. are calculated using digital signal processing techniques, giving an
      idea of the degree of hoarseness and quality of the voice register. Within this
      framework, the system uses a standard protocol to evaluate and build complete
      databases of voice disorders. The target users of this system are speech and
      language therapists and ear nose and throat (ENT) clinicians. The application can
      be easily configured to cover the needs of both groups of professionals. The
      software has a user-friendly Windows style interface. The PC should be equipped
      with standard sound and video capture cards. Signals are captured using common
      transducers: a microphone, an electroglottograph and a fiberscope or
      telelaryngoscope. The clinical usefulness of the system is addressed in a
      comprehensive evaluation section.

PMID- 15950514
TI  - Patterns of illicit drug use of prisoners in police custody in London, UK.
AB  - AIMS AND METHODS: The aims of the study were to explore the current
      characteristics of drug misusers seen in police custody and identify trends or
      changes that have taken place in the last decade. A prospective, anonymised,
      structured questionnaire survey was undertaken of consenting consecutive, self
      admitted illicit drug users seen by forensic physicians in police custody within
      the Metropolitan Police Service in London, UK in 2003. RESULTS: 30% of detainees
      were dependent on heroin or crack cocaine. Drug users (n=113) were studied in
      2003. 95.4% completed the questionnaire. 82% were male, 18% female. Mean age was
      28.5 y (range 18-49). 80% were unemployed; significant mental health issues
      (e.g., schizophrenia) were present in 18%; 15% had alcohol dependence; heroin was
      the most frequently used drug (93%); crack cocaine -- 87%; mean daily cost of
      drugs -- heroin GBP 76 (range 20-240), crack GBP 81 (range 20-300). >50% users
      inject crack and heroin simultaneously. 56% used the intravenous route; 25% had
      shared needles; 100% had accessible sources of clean needles; 6.4% were hepatitis
      B positive; 42% were aware of hepatitis prophylaxis; hepatitis C positive --
      20.2%; 3.6% were HIV positive. Mean length of time of drug use was 7.5 y (range 1
      month -- 20 years); 82% had served a previous prison sentence; 54% had used drugs
      in prison; 11% had used needles in prison; 3% of users stated they had started
      using in prison. 38% had been on rehabilitation programs; 11% had been on Drug
      Treatment and Testing; Orders (DTTO); 32% had used the services of Drug Arrest
      Referral Teams in police stations; 10% were in contact with Drug Teams at the
      time of assessment. CONCLUSIONS: In the last decade, there appears to be a
      substantial increase in the prevalence of drug use in this population --
      particularly of crack cocaine. Treatment interventions are either not readily
      available, or not followed through. In very general terms, the illicit drug use
      problem appears to have significantly worsened in the population seen in police
      custody in London, UK, in the last decade although there is evidence that health
      education and harm reduction messages appear to have had some positive effects.

PMID- 15950515
TI  - Integrating dementia care in England and The Netherlands: four comparative local
      case studies.
AB  - The article presents a cross-national comparative study of the implementation of
      integrated dementia care at local level in England and The Netherlands. Four
      local case studies (Amsterdam Nieuw West, Leeds West, Maastricht, York) focus on
      the interaction between the respective national policies with local contexts and
      policy processes, in order to explain the variety of local outcomes regarding
      integrated dementia care. Localities are shown as entities with particular
      institutional contexts and histories (i.e. local configurations), which have
      specific impacts on processes of policy implementation within the respective
      national health and social care systems.

PMID- 15950516
TI  - A simultaneous analysis of neighbourhood and childhood socio-economic environment
      with self-assessed health and health-related behaviours.
AB  - Childhood socio-economic environment and neighbourhood socio-economic environment
      later in life are closely related. However, few studies have considered their
      effects simultaneously. Using cross-sectional data of approximately 8000
      respondents in 86 neighbourhoods in the city of Eindhoven, The Netherlands, we
      study associations of both determinants with self-assessed health, smoking,
      alcohol consumption and overweight. Growing up in a low socio-economic
      environment increased the probability to live a more deprived neighbourhood in
      adulthood. Controlling for individual socio-economic characteristics, both
      childhood and neighbourhood socio-economic environment were related to smoking
      and overweight, but not with excessive alcohol consumption. Associations between
      childhood socio-economic environment and smoking and overweight are still
      substantial after controlling for neighbourhood socio-economic environment.
      Similarly, neighbourhood inequalities in smoking and overweight remain
      substantial after controlling for childhood socio-economic environment.

PMID- 15950517
TI  - Diagnostic value of five clinical tests in patellofemoral pain syndrome.
AB  - The current study is aimed at examining the validity of five clinical
      patellofemoral tests used in the diagnosis of patellofemoral pain syndrome
      (PFPS). Forty-five knee patients were divided into either the PFPS or the non
      PFPS group, based on the fulfilment of the diagnostic criteria for PFPS. An
      investigator, blinded to the group assignment, performed the vastus medialis
      coordination test, patellar apprehension test, Waldron's test, Clarke's test, and
      the eccentric step test. The positive likelihood ratio was 2.26 for both the
      vastus medialis coordination test and the patellar apprehension test. For the
      eccentric step test, the positive likelihood ratio was 2.34. A positive outcome
      on either the vastus medialis coordination test, the patellar apprehension test,
      or the eccentric step test increases the probability of PFPS to a small, but
      sometimes important, degree. For the remaining tests, the positive likelihood
      ratios were below the threshold value of 2, indicating that given a positive test
      result, the probability that the patient has PFPS is altered to a small, and
      rarely important degree. The negative likelihood ratios for all tests exceeded
      the threshold value of 0.5, suggestive of clinically irrelevant information.
      These data question the validity of clinical tests for the diagnosis of PFPS.

PMID- 15950518
TI  - Cardiomyocytes structure, function and associated pathologies.
AB  - The heart is the first formed organ in the developing fetus. During fetal and
      postnatal development cardiomyocytes become terminally differentiated muscular
      cells that are connected end to end by gap junctions, allowing concerted
      contractile activity. The contraction-relaxation cycle of cardiomyocytes is
      orchestrated by cyclic increases and decreases in intracellular Ca(2+) initiated
      by depolarization of the sarcolemma and sustained by Ca(2+) release and re-uptake
      by the sarcoplasmic reticulum. When stressed, cardiomyocytes undergo hypertrophic
      growth and apoptotic responses in vivo as well as in cell culture models. Such
      changes predispose to heart failure in the longer term.

PMID- 15950519
TI  - Tailoring the plant metabolome without a loose stitch.
AB  - Metabolic engineering holds great promise as a technique for improving crop
      plants. However, introducing new metabolic steps can disturb normal metabolism
      and gene expression, affecting phenotype and quality in undesired ways. Recently,
      Charlotte Kristensen et al. reported that introducing the sorghum pathway for
      biosynthesis of the cyanogenic glucoside dhurrin into Arabidopsis plants resulted
      in high dhurrin levels and only marginal side effects on the metabolome and the
      transcriptome.

PMID- 15950520
TI  - Sorting of proteins to storage vacuoles: how many mechanisms?
AB  - Vacuoles receive their proteins through the secretory pathway, this requires
      protein sorting signals and molecular machineries that, until recently, have been
      believed to be markedly distinct for lytic and storage vacuoles. However, new
      biochemical, morphological and genetic data indicate that the only known class of
      vacuolar sorting receptors, believed to be specific for lytic vacuoles, might
      also be involved in the sorting of certain storage proteins. Furthermore, storage
      vacuoles can have a complex multimembrane structure that is difficult to explain
      based on a single trafficking mechanism. A new array of possible molecular
      interactions is thus emerging that no longer supports a clear-cut distinction
      between the two types of vacuoles based on sorting signals and putative
      receptors.

PMID- 15950521
TI  - Non-invasive visualization of collateral blood flow patterns of the circle of
      Willis by dynamic MR angiography.
AB  - The circle of Willis plays an important role in the distribution of blood flow in
      the brain. To obtain dynamic information of the blood flow through the circle of
      Willis, a dynamic MRA technique based on arterial spin labeling (ASL) is
      introduced as a non-invasive technique. When the ASL labeling slab is restricted
      to a single artery, it is possible to visualize selectively the flow distribution
      of that specific artery. However, because of the decay of the label and the
      presence of noise it is difficult to extract functional information from these
      images. In the present study we propose three visualization and post-processing
      methods for the interpretation of these images. Firstly, the passage of labeled
      blood was corrected for decay of the label and hereafter shown as a movie.
      Secondly, by calculating the time of arrival at every location in the arteries of
      the circle of Willis, a 2D image was reconstructed summarizing the information of
      the movie. Finally, quantitative flow values were obtained by relating the
      arterial input function to the passage of labeled blood through a region of
      interest encompassing the vessel under investigation. Experiments in a circle of
      Willis phantom showed a high linear relation between measured flow and true flow,
      although the measured values were 10-15% lower than the true flow values.
      Measurements in healthy volunteers showed the potential to quantify the flow in
      all major arteries of the circle of Willis.

PMID- 15950522
TI  - Predictive, non-GLP models of secondary pharmacodynamics: putting the best
      compounds forward.
AB  - Secondary pharmacodynamic studies of new chemical entities (NCEs) play a critical
      role in support of efficient drug discovery. In an era in which speed and
      efficiency are the norm for pharmaceutical discovery, the need to identify NCEs
      with greater patient tolerability continues to increase. Early use of secondary
      pharmacodynamic models (in vivo and in vitro) provides the foundation for
      critical, early decisions regarding lead molecules. Scientifically robust, non
      GLP (good laboratory practices) secondary pharmacodynamic studies can eliminate
      compounds or structural series with undesirable profiles early, and may prove
      useful in defining structure-activity relationships (SARs) with regards to off
      target effects.

PMID- 15950523
TI  - FT-IR spectroscopic study on the variations of molecular structures of some
      carboxyl acids induced by free electron laser.
AB  - Free electron laser has been developed as tunable lasers over a wide range of
      wavelengths. Devices irradiating in the region of 6-16 microm (1666-625 cm-1) are
      operable in the Beijing free electron lasers facilities (BFEL). For understanding
      the interactions between FEL and biological tissues, in this study wavelength
      selective infrared-induced structure changes of substances under irradiation by
      FEL were measured using FT-IR spectroscopy. The carboxyl acids and carboxylates
      samples investigated include salicylic acid, sulfosalicylic acid, cholic acid,
      deoxycholic acid, sodium cholate and sodium deoxycholate. The changes of the FT
      IR spectra of the molecules prove that the spectral variations of the samples
      induced by FEL are closely related to their hydrogen bond networks.

PMID- 15950524
TI  - Anisotropy shift and Raman bandwidth studies in carbonyl containing molecule o
      chlorobenzaldehyde: role of repulsive forces.
AB  - The analysis of Raman anisotropy shift as a function of solvent concentration
      shows the weakening of pair interaction of the molecules due to the influence of
      solvent-induced perturbations. The present study deals with the effect of
      dielectric constant of the medium on the non-coincidence effect (anisotropy
      shift) and the role of van der Waals' volume on the anisotropic Raman bandwidth.
      The CO stretching vibration of o-chlorobenzaldehyde (OCBD) molecule was studied
      in various polar and non-polar solvents namely CCl4, CH3CN, C6H5Cl and CH3C6H5.
      The data on anisotropic bandwidth are interpreted using the van der Waals' volume
      within the framework of lineshape theory of Bratos and Tarjus, while the Onsager
      Frohlich model on non-coincidence effect has been tested. Our study shows that
      the repulsive potential of the type e-alphaR is playing an important role in the
      OCBD-solvent interactions. The vanishing of anisotropy shift (non-coincidence
      effect) on dilution may be explained on the basis of repulsive forces playing a
      significant role in solute-solvent interactions.

PMID- 15950525
TI  - Solution and solid-state NMR studies of some cadmium-selenone complexes.
AB  - Cadmium(II) complexes of Imidazolidine-2-selenone (ImSe) and its derivatives have
      been prepared with the general formula Cd(RImSe)2Cl2 (where R=Me, Et, Pr, etc.).
      These complexes are characterized by elemental analysis, IR and NMR (1H, 13C,
      77Se and 113Cd) spectroscopy. An upfield shift in C=Se resonance of selenones in
      13C NMR and in 77Se and high-frequency shifts in N-H resonances in 1H are
      consistent with the selenium coordination to Cd(II). The 77Se nucleus in
      Cd(ImSe)2Cl2 is shielded by 38 ppm on coordination, relative to the free ligand.
      The principal components of the 77Se, 113Cd and 13C shielding tensors for the
      complexes were determined from solid-state NMR data. Large selenium chemical
      shift anisotropies were observed for these complexes.

PMID- 15950526
TI  - Structural studies of E. coli ribosomes by spectroscopic techniques: a
      specialized review.
AB  - We present a review on our interdisciplinary line of research based on strategies
      of molecular biology and biophysics. These have been applied to the study of the
      prokaryotic ribosome of the bacterium Escherichia coli. Our investigations on
      this organelle have continued for more than a decade and we have adopted
      different spectroscopic biophysical techniques such as: dielectric and
      fluorescence spectroscopy as well as light scattering (photon correlation
      spectroscopy). Here we report studies on the whole 70S ribosomes and on the
      separated subunits 30S and 50S. Our results evidence intrinsic structural
      features of the subunits: the small shows a more "floppy" structure, while the
      large one appears to be more rigid. Also, an inner "kernel" formed by the
      RNA/protein association is found within the ribosome. This kernel is surrounded
      by a ribonucleoprotein complex more exposed to the solvent. Initial analyses were
      done on the so called Kaldtschmit-Wittmann ribosome: more recently we have
      extended the studies to the "tight couple" ribosome known for its better
      functional performance in vitro. Data evidence a phenomenological correlation
      between the differential biological activity and the intrinsic structural
      properties of the two-ribosome species. Finally, investigations were also
      conducted on particles treated at sub-denaturing temperatures and on ribosomes
      partially deproteinized by salt treatment (ribosomal cores). Results suggest that
      the thermal treatment and the selective removal of proteins cause analogous
      structural alterations.

PMID- 15950527
TI  - Spectroscopic studies on 2,3,4,5-tetraphenylpyrylium salts with and without
      silver (I)-bridged structures.
AB  - Two novel phenylated pyrylium compounds, silver (I)-bridged 2,3,4,5
      tetraphenylpyrylium perchlorate (P1) and its silver (I)-free pyrylium ligand (P2)
      were prepared from 1,2,3,4-tetraphenylcyclopentadiene to examine their
      spectroscopic behaviors. The UV/vis absorption and fluorescent emission spectra
      of P1 and P2, measured in three solvents (acetonitrile, dichloromethane and
      toluene), reveal that the photophysical behaviors are closely related to silver
      (I) fragment, and strongly dependent on solvent polarity. In polar acetonitrile,
      P1 displays longer absorption wavelength and much lower fluorescent emission
      intensity than P2, although they exhibit much similarity in shape. In contrast,
      in nonpolar toluene, while P2 shows an apparent absorption band at 338 nm, P1
      displays a tail-like line without absorption band observed. All the spectra
      obtained indicate a better coplanarity and a stronger intra-molecular charge
      transfer in P1 due to the effect of silver (I) fragment. Additionally, the 1H NMR
      spectra of P1 and P2, which were recorded under the same conditions, indicate
      that the silver (I) fragment reinforces pyrylium ring's capacity to localize the
      formal positive charge within the heterocyclic ring.

PMID- 15950528
TI  - New triorganotin (IV) derivatives of dipeptides as models for metal-protein
      interactions: synthesis, structural characterization and biological studies.
AB  - New non-electrolytic triorganotin(IV) derivatives of dipeptides with general
      formulae R3Sn(HL), where R = Ph and HL = monoanion of glycylisoleucine (H2L-1),
      valylvaline (H2L-2), alanylvaline (H2L-3), leucylalanine (H2L-4), leucylleucine
      (H2L-5); R = n-Bu and HL = monoanion of glycylisoleucine (H2L-1) and
      leucylalanine (H2L-4); and R = Me and HL = monoanion of leucylalanine (H2L-4)
      have been synthesized and characterized on the basis of infrared, multinuclear
      1H, 13C and 119Sn NMR and 119Sn Mossbauer spectroscopic studies. These
      investigations suggest that all the ligands in R3Sn(HL) act as monoanionic
      bidentates coordinating through the COO- and NH2 groups. The 119Sn Mossbauer
      studies, together with the NMR data, indicate that, for these polymeric
      derivatives, the polyhedron around tin in R3Sn(HL) is a trigonal-bipyramid with
      the three organic groups in the equatorial positions, while the axial positions
      are occupied by a carboxylic oxygen and the amino nitrogen atom from the adjacent
      molecule. The anti-inflammatory and cardiovascular activities and toxicity of all
      these compounds have been determined. Four of the complexes have also been
      screened against some of the chosen bacterial and fungal strains. The Ph3Sn(IV)
      compounds exhibit better anti-inflammatory and cardiovascular activities in
      comparison to the Me3Sn(IV) and n-Bu3Sn(IV) analogues. n-Bu3Sn(Gly-Ile) and
      Ph3Sn(Ala-Val) exhibit good antibacterial activity against all the chosen
      strains.

PMID- 15950529
TI  - Studies on the interaction of colloidal gold and serum albumins by spectral
      methods.
AB  - The interactions of colloidal gold and serum albumins, including bovine serum
      albumin (BSA) and human serum albumin (HSA), were studied by fluorescence and
      absorption spectrometry. Fluorescence quenching spectrometry was applied to study
      the interactions between colloidal gold and serum albumins. At pH 7.4 phosphate
      buffered saline (PBS), the intensity of fluorescence emission spectrum of serum
      albumins decreased in the presence of colloidal gold, which indicated that
      colloidal gold quenched the fluorescence of serum albumins. Experimental results
      indicated that the combination reactions of colloidal gold and serum albumins
      were static quenching processes. Based on the effect of colloidal gold on
      fluorescence intensity, the binding constants, the numbers of binding sites and
      the acting forces between colloidal gold and serum albumins were found.

PMID- 15950530
TI  - Determination of dipole moment in the ground and excited state by experimental
      and theoretical methods of N-nonyl acridine orange.
AB  - The absorption and fluorescence spectra of N-nonyl acridine orange are determined
      at room temperature (298 K) in cyclohexane, benzene, carbon tetrachloride,
      chloroform, chlorobenzene and dichloromethane. The ground state of dipole moment
      was obtained by impedance measurements using Guggenheim-Debeye's method. The
      experimental excited state dipole moment of N-nonyl acridine orange was
      determined using Bakhshiev's and Kawski-Chamma-Viallet's formulae and solvent
      polarity parameter proposed by Reichardt. These experimental results were
      completed with theoretical results using quantum chemical methods. The
      experimental (muexp=10.76 D) and theoretical (mucal=9.9 D) dipole moments in the
      ground and excited state (muexp*=14.56 D) were compared.

PMID- 15950531
TI  - Structural and up-conversion luminescence properties in Tm3+/Yb3+-codoped heavy
      metal oxide-halide glasses.
AB  - Tm3+/Yb3+-codoped heavy metal oxide-halide glasses have been synthesized by
      conventional melting and quenching method. Structural properties were obtained
      based on the Raman spectra, indicating that halide ion has an important influence
      on the phonon density and maximum phonon energy of host glasses. Intense blue and
      weak red emissions centered at 477 and 650 nm, corresponding to the transitions
      1G4-->3H6 and 1G4-->3H4, respectively, were observed at room temperature. The
      possible up-conversion mechanisms are discussed and estimated. With increasing
      halide content, the up-conversion luminescence intensity and blue luminescence
      lifetimes of Tm3+ ion increase notably. Our results show that with the
      substitution of halide ion for oxygen ion, the decrease of phonon density and
      maximum phonon energy of host glasses both contribute to the enhanced up
      conversion emissions.

PMID- 15950532
TI  - Conformational study of galphimines A and B.
AB  - A conformational study has been performed for galphimines A and B, which differ
      from each other only in an acetate moiety on ring B of galphimine A. Mechanical
      molecular calculations showed that the predominant conformers in a Boltzman
      distribution are those which establish an intramolecular hydrogen bond between
      the hydroxyls on rings A and B, keeping a similar conformation on the rest of the
      molecule. The existence of these conformers was confirmed by NMR spectroscopy in
      (D6) DMSO solution. Furthermore, an unbound hydrogen conformation was found.
      These types of conformations very probably coexist in solution, for both types of
      galphimines A and B. Additional experiments suggest that the acetate group on
      galphimine A does not distort rings B and A, neither does it disturb the
      intramolecular hydrogen bond formation that also shows galphimine B. Finally, it
      does not present a steric effect on ring A to avoid any type of interaction of
      the functional groups on this ring with the biological receptor. The acetate
      group, which is responsible for the lost of activity of galphimine A very
      probably prevent that the hydroxyls OH4 and OH7 from interacting, either in a
      hydrogen bounded or free form, with the receptor, indicating the importance that
      these hydroxyls play in the biological activity of the molecule.

PMID- 15950533
TI  - Collagen absorption bands in heated and rehydrated dentine.
AB  - The objective of this work is identifying changes in the collagen bands in heated
      and rehydrated dentine. We use bovine dentine slices that were heated in oven
      between 100 and 300 degrees C. The sample hydration was conducted in sodium
      chloride solution at 0.9 wt.%; the spectra were acquired by a Fourier transform
      infrared spectrometer in the spectral range of 4000-400 cm-1. Our results show a
      temperature range (T<or=175 degrees C) where the dentinal collagen can be
      partially denatured and reverted to initial conformation; a second region (175
      degrees C<T<or=225 degrees C) where this process occurs partially and a third
      region (T>225 degrees C) where the collagen is denatured and no reversion is
      observed after rehydration. This work identifies an important characteristic that
      dentinal collagen can assume when the tissue is heated and rehydrated; these
      results indicate the denaturation temperature of dentinal collagen to be near 175
      200 degrees C.

PMID- 15950534
TI  - Up-conversion luminescence analysis in ytterbium-sensitized erbium-doped oxide
      halide tellurite and germanate-niobic-lead glasses.
AB  - Ytterbium-sensitized erbium-doped oxide-halide tellurite and germanate-niobic
      lead glasses have been synthesized by conventional melting method. Intense green
      and red emissions centered at 525, 546 and 657 nm, corresponding to the
      transitions 2H11/2-->4I15/2, 4S3/2-->4I15/2 and 4F9/2-->4I15/2, respectively,
      were simultaneously observed at room temperature in these glasses. The quadratic
      dependence of the 525, 546 and 657 nm emissions on excitation power indicates
      that a two-photon absorption process occurs. Tellurite glass showed a weaker up
      conversion emission than germanate-niobic-lead glass, which is inconsistent with
      the prediction from the difference of maximum phonon energy between tellurite and
      germanate-niobic-lead glasses. In this paper, Raman spectroscopy was employed to
      investigate the origin of the difference in up-conversion luminescence in the two
      glasses. Compared with phonon side-band spectroscopy, Raman spectroscopy extracts
      more information including both phonon energy and phonon density. Our results
      reveal that the phonon density and the maximum phonon energy of host glasses are
      both important factors in determining the up-conversion efficiency.

PMID- 15950535
TI  - Density functional theory study of vibrational spectra, and assignment of
      fundamental vibrational modes of succinimide and N-bromosuccinimide.
AB  - This work deals with the vibrational spectroscopy of succinimide and N
      bromosuccinimide. The mid and far FTIR and FT-Raman spectra were measured in the
      condensed state. The fundamental vibrational frequencies and intensity of
      vibrational bands were evaluated using density functional theory (DFT) using
      standard B3LYP/6-31G(*) and B3LYP/6-311+G(**) methods and basis set combinations.
      The vibrational spectra were interpreted, with the aid of normal coordinate
      analysis based on a scaled quantum mechanical force field. The infrared and Raman
      spectra were also predicted from the calculated intensities. Comparison of
      simulated spectra with the experimental spectra provides important information
      about the ability of the computational method to describe the vibrational modes.
      Unambiguous vibrational assignment of all the fundamentals were made using the
      total energy distribution (TED).

PMID- 15950536
TI  - Charge transfer complexes of adenosine-5'-monophosphate and cytidine-5'
      monophosphate with water-soluble cobalt(II) Schiff base complexes in aqueous
      solution.
AB  - Water-soluble cobalt(II) tetradentate Schiff base complexes have been shown to
      form charge transfer (CT) complexes with a series of nucleoside monophosphates
      including adenosine-5'-monophosphate (AMP) and cytidine-5'-monophosphate (CMP).
      The investigated water-soluble cobalt(II) Schiff base complexes are (i)
      disodium[{bis(5-sulfo-salicylaldehyde)-o-phenylenediiminato}cobalt(II)],
      Na2[Co(SO3-salophen)] (1); (ii) disodium[{bis(5-sulfo-salicylaldehyde)-4,5
      dimethyl-o-phenylenediiminato}cobalt(II)], Na2[Co(SO3-sal-4,5-dmophen)] (2) and
      (iii) disodium[{bis(4-methoxy-5-sulfo-salicylaldehyde)-4,5-dimethyl-o
      phenylenediiminato}cobalt(II)], Na(2)[Co(SO3-4-meosal-4,5-dmophen)] (3). The
      formation constant and thermodynamic parameters for charge transfer complex
      formation of water-soluble cobalt(II) Schiff base complexes with nucleoside
      monophosphates were determined spectrophotometrically in aqueous solution at
      constant ionic strength (I = 0.2 mol dm(-3) KNO3) under physiological condition
      (pH 7.0) and at various temperatures between 288 and 308 K. The stoichiometry has
      been found to be 1:1 (water-soluble cobalt(II) Schiff base complex: nucleoside
      monophosphate) in each case. Our spectroscopic and thermodynamic results show
      that the interaction of water-soluble cobalt(II) Schiff base complexes with the
      investigated nucleoside monophosphates occurs mainly through the phosphate group.
      The trend of the interaction according to the cobalt(II) Schiff base complexes
      due to electronic and steric factors is as follows: Na2[Co(SO3-salophen)] >
      Na2[Co(SO3-sal-4,5-dmophen)] > Na2[Co(SO3-4-meosal-4,5-dmophen)]. Also the trend
      of the interaction of a given cobalt(II) Schiff base complex according to the
      nucleoside monophosphate is as follows: CMP > AMP.

PMID- 15950537
TI  - 2n-fatty acids from phosphatidylcholine label sphingolipids--a novel role of
      phospholipase A2?
AB  - In order to find out whether there is a phospholipase A2 (PLA2)-mediated link
      between glycerophospholipids and sphingolipids, L929 cells were labeled with 1n
      palmitoyl-2n-[1-14C]palmitoyl phosphatidylcholine for 16-18 h or 90 min. After
      labeling for 16-18 h, 14C-sphingomyelin (SM), 14C-ceramide and 14C-sphingosine
      were demonstrated on autoradiograms of thin layer chromatograms of untreated or
      mildly hydrolyzed lipid extracts in different chromatographic systems. Strong
      hydrolysis of labeled SM proved that both possible moieties of SM, sphingosine
      and acyl moiety, had been labeled. The identity of SM and its enzymatic
      degradation product, ceramide, was verified by mass spectrometry. The label in SM
      derived ceramide was demonstrated on an autoradiogram after thin layer
      chromatography. The inhibitor of (dihydro)ceramide synthase fumonisin B1
      suppressed the label in sphingolipids significantly during 16-18 h (ceramide and
      SM), as well as during 90-min labeling (SM). The presence of inhibitors of PLA2
      (bromoenol lactone, aristolochic acid and quinacrine dihydrochloride) diminished
      the label in SM significantly during the 90-min labeling. These results
      demonstrate a close metabolic relationship between glycerophospholipids and
      sphingolipids and give evidence for a novel role of PLA2.

PMID- 15950538
TI  - Recent developments related to the EGFR as a target for cancer chemotherapy.
AB  - Inhibition of the epidermal growth factor receptor as a target for cancer
      chemotherapy has proven to be an effective treatment in both preclinical and
      clinical settings. Recent work has indicated that the presence of somatic
      mutations in the tyrosine kinase domain of the epidermal growth factor receptor
      is a major determinant of the response to the tyrosine kinase inhibitors
      gefitinib and erlotinib. However, this is not the full story, and further work is
      needed to identify the factors underlying the response in those who do not carry
      mutations. Mechanisms of innate and acquired resistance to epidermal growth
      factor receptor inhibitors are also topics under investigation. Crosstalk between
      the epidermal growth factor receptor and other growth factor receptors involved
      in tumorigenesis has been implicated, along with downstream signalling molecules
      such as Ras, Braf and PTEN. A full understanding of these mechanistic aspects
      could lead to the identification of useful combinations of inhibitors of novel
      targets.

PMID- 15950539
TI  - Targeted therapy for colorectal cancer: mapping the way.
AB  - In spite of the significant advances in conventional therapeutic approaches to
      colorectal cancer (CRC), most patients ultimately die of their disease.
      Dissecting the molecular mechanisms underlying CRC progression will not only
      accelerate the development of novel cancer-selective drugs but will also enable
      the therapeutic regimen to be personalized according to the molecular features of
      individual patients and tumors. Here, we report on the novel insights into CRC
      biology that are paving the way to the development of molecular therapies and
      summarize the results from recent clinical trials demonstrating that agents
      targeting tumor-specific molecular derangements can significantly improve the
      therapeutic efficacy of conventional chemotherapy. Only a broader clinical
      implementation of these concepts will provide patients with CRC the best chance
      of a cure.

PMID- 15950540
TI  - Sense of coherence and health-related quality of life among patients undergoing
      coronary artery bypass grafting or angioplasty.
AB  - BACKGROUND: Every year, 4 million people die from cardiovascular disease (CAD) in
      Europe. As many as 800,000 of them die before they reach the age of 65. The
      ischemic heart disease is also the most common cause of death in Finland. The
      invasive treatments of the CAD, coronary artery bypass grafting (CABG) and
      percutaneous transluminal coronary angioplasty (PTCA) relieve symptoms and
      increase patient's health-related quality of life (HRQoL) in most of the cases.
      In this paper sense of coherence is discussed as related to health-related
      quality of life among CABG and PTCA patients in a one-year follow-up. SAMPLE: The
      study sample consisted of consecutive male (N=439) and female (N=176) patients
      who were treated with the elective CABG or PTCA. The baseline data before the
      interventions were collected by structured interviews, the follow-up data by
      mailed self-administered questionnaires six and twelve months afterwards.
      MEASURES: The sense of coherence was studied by using a 13-item SOC scale. HRQoL
      was measured by the 15D. It is a generic, multidimensional, standardized, self
      administered instrument, which has both a profile and single index score
      property. The differences in both groups were defined by using T-tests. Follow-up
      outcomes were analysed by using analyses of variance for repeated measures.
      RESULTS: Health-related quality of life increased in both groups during the
      follow-up. There was a correlation between health-related quality of life and
      sense of coherence in CABG and PTCA patients' group at baseline. The mean score
      of the 15D was lower in moderate sense of coherence tertile than in strong sense
      of coherence tertile in both groups. After six and twelve months the similar
      tendency existed in health-related quality of life and sense of coherence;
      patients who had poor or moderate sense of coherence had lower health-related
      quality of life than the patients with strong sense of coherence. CONCLUSIONS:
      Sense of coherence was more stable among CABG patients than PTCA patients. In
      PTCA patients' group sense of coherence decreased during the follow-up time. In
      both patients' group the health-related quality of life increased statistically
      significant by 6 months. No significant change in health-related quality of life
      took place in either group from 6 to 12 months.

PMID- 15950541
TI  - Efficient gene transfer into mouse embryonic stem cells with adenovirus vectors.
AB  - Efficient and transient gene transfer into embryonic stem (ES) cells is expected
      to be of use for basic studies in developmental biology and for applications in
      regenerative medicine. Here, we report the development of an adenovirus (Ad)
      vector that efficiently expresses foreign genes in mouse ES (mES) cells. We
      prepared four LacZ-expressing Ad vectors, each of which contained one of the
      following: Rous sarcoma virus (RSV), cytomegalovirus (CMV), beta-actin
      promoter/CMV enhancer (CA), or EF-1alpha promoter. While the RSV and CMV
      promoters were inactive in mES cells, the CA and EF-1alpha promoters strongly
      drove LacZ expression in more than 90% of the mES cells. The EF-1alpha promoter
      was found to be slightly more efficient than the CA promoter. mES cells were
      found to express the Ad primary receptor, coxsackievirus and adenovirus receptor,
      suggesting that while Ad vectors could introduce the exogenous gene into mES
      cells, the choice of a suitable promoter was critical for efficient gene
      expression. Fiber-mutant Ad vectors containing RGD or polylysine peptide on the
      fiber knob mediated efficient LacZ expression, not only in mES cells, but also in
      feeder cells. Exogenous expression of Oct-3/4 or the dominant-negative mutant of
      STAT3 (STAT3F) by conventional Ad vectors containing the EF-1alpha promoter
      promoted the differentiation of mES cells into the cells of three germ layers,
      and STAT3F-mediated differentiation was rescued by the coexpression of Nanog.
      These results suggest that Ad vectors can be used for basic research using ES
      cells and that they may be of great utility for therapeutic applications in gene
      modified regenerative medicine based on ES cells.

PMID- 15950543
TI  - Type I interferons potently suppress gene expression following gene delivery
      using liposome(-)DNA complexes.
AB  - Gene delivery by intravenous injection of cationic liposome-DNA complexes (LDC)
      can generate efficient transgene expression in the lungs and other organs, but
      the duration of expression is typically short. Previous studies have suggested a
      major role for interferon-gamma (IFN-gamma) and TNF in this process. However,
      plasmid DNA is also capable of eliciting production of type I IFNs. Therefore, we
      assessed the ability of LDC to elicit production of type I IFNs in vivo and
      assessed the effects of type I IFNs on suppression of transgene expression
      following in vivo gene delivery with LDC. Injection of LDC was found to induce
      production of high levels of both IFN-alpha and IFN-beta in vivo. Moreover, the
      levels of transgene expression following in vivo gene delivery were markedly
      increased in mice lacking functional type I IFN receptor genes, compared to wild
      type mice or mice lacking IFN-gamma or TNF receptors. Addition of recombinant IFN
      alpha and IFN-beta inhibited transgene expression by in vitro-transfected
      endothelial cells, and incubation of macrophages with LDC in vitro triggered
      production of both IFN-alpha and IFN-beta. Therefore, type I IFNs appear to play
      a key role in suppressing transgene expression in vivo following systemic
      nonviral gene delivery using LDC.

PMID- 15950544
TI  - Failure of multiple coronary angiographies to identify left main coronary artery
      disease in a patient diagnosed by transesophageal echocardiography.
AB  - This case report describes the role of transesophageal echocardiography to
      diagnose proximal left main coronary artery disease.

PMID- 15950542
TI  - Plasmid delivery in vivo from porous tissue-engineering scaffolds: transgene
      expression and cellular transfection.
AB  - Tissue engineering scaffolds capable of sustained plasmid release can promote
      gene transfer locally and stimulate new tissue formation. We have investigated
      the scaffold design parameters that influence the extent and duration of
      transgene expression and have characterized the distribution of transfected
      cells. Porous scaffolds with encapsulated plasmid were fabricated from
      poly(lactide-co-glycolide) with a gas foaming procedure, with wet granulation
      employed to mix the components homogeneously prior to foaming. Wet granulation
      enhanced plasmid incorporation relative to standard procedures and also enhanced
      in vivo transgene expression, possibly through the increased loading and
      maintenance of the scaffold pore structure. The plasmid loading regulated the
      quantity and duration of transgene expression, with expression for 105 days
      achieved at the highest dosage. Expression was localized to the implantation
      site, though the distribution of transfected cells varied with time. Transfected
      cells were initially observed at the scaffold periphery (day 3), then within the
      pores and adjacent to the polymer (day 17), and finally throughout the scaffold
      interior (day 126). Delivery of a plasmid encoding VEGF increased the blood
      vessel density relative to control. Correlating scaffold design with gene
      transfer efficiency and tissue formation will facilitate application of plasmid
      releasing scaffolds to multiple tissues.

PMID- 15950545
TI  - Hepatic and renal cadmium accumulation is associated with mass-specific daily
      metabolic rate in the bank vole (Clethrionomys glareolus).
AB  - Previous study has shown that photoperiod and age affect tissue accumulation of
      cadmium (Cd) in a small rodent, the bank vole. Since the body mass is also
      influenced by these factors, the present study was designed to determine whether
      mass-specific daily metabolic rate might be responsible for differential
      accumulation of Cd in the liver and kidneys of the short- and long-photoperiod
      bank voles as well as of the young and old animals. One- and five-month old male
      bank voles were held under short (8 h light/16 h dark) or long (16 h light/8 h
      dark) photoperiods and exposed to dietary Cd (100 microg/g) for 6 weeks. The bank
      voles raised under the short photoperiod and those injected subcutaneously with
      melatonin (7 micromol/kg/day) under the long photoperiod showed significantly
      higher concentrations of Cd in the liver (43-60%) and kidneys (40-47%) than the
      age-matched long-photoperiod animals. The old bank voles accumulated
      significantly less Cd in both organs than the young animals. These differences in
      Cd accumulation appeared not to be associated with the relative Cd intake.
      However, the hepatic and renal Cd levels followed a pattern similar to that of
      the mass-specific daily metabolic rate (or energy expenditure) and energy
      assimilation efficiency. These data indicate that mass-specific daily metabolic
      rate and energy assimilation efficiency (an indicative of digestive and
      absorptive processes) may be responsible for differential tissue Cd accumulation
      in the bank vole.

PMID- 15950546
TI  - Characterization of natural chitosan membranes from the carapace of the soldier
      crab Mictyris brevidactylus and its application to immobilize glucose oxidase in
      amperometric flow-injection biosensing system.
AB  - This study investigated characteristics of a chitosan membrane from the carapace
      of the soldier crab Mictyris brevidactylus intended to construct an amperometric
      biosensor. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry
      (CV) were used in this study to characterize these chitosan membranes intended
      for constructing enzymatic biosensors. Chitosan membranes suffering various
      durations (>10 min) of deacetylation had small charge-transfer resistances (<7.88
      kohms) but large double-layer capacitances (>0.55 microF). They were found in EIS
      where both the solution resistance and Warburg impedance upon electrode interface
      were almost independent of the durations and degree of deacetylation. The degree
      of deacetylation and the thickness of chitosan membranes were also determined.
      Membrane thickness was slightly dependent with the duration but degree of
      deacetylation was slightly dependent on the duration. Chitosan membranes with
      various thicknesses suffered various durations of deacetylation, but this did not
      influence their electrochemical characteristics. The chitinous membrane was
      covalently immobilized with glucose oxidase (EC 1.3.4.3) and then attached onto
      the platinum electrode of a homemade amperometric flow cell. Sensor signal was
      linearly related to glucose concentration (r=0.999 for glucose up to 1.0 mM). The
      system was sensitive (S/N>5 for 10 microM glucose) and reproducible (CV<1.3% for
      50 microM glucose, n=5).

PMID- 15950547
TI  - Selective response of dopamine in the presence of ascorbic acid at multi-walled
      carbon nanotube modified gold electrode.
AB  - The acid-treated multi-walled carbon nanotubes (MWNTs), which were modified on
      the surface of gold electrode, offers substantial improvements in voltammetric
      sensitivity and selectivity towards the determination of dopamine (DA). It can
      inhibit the voltammetric response of ascorbic acid (AA) while the redox reaction
      of dopamine is promoted. When a differential pulse voltammetric (DPV) technique
      was used, the peak separation between DAs and AAs was 244 mV. Based on this, a
      selective method could be constructed to detect DA in the presence of 1,000 times
      higher concentration of AA. The effect of various experimental parameters on the
      voltammetric response of dopamine was investigated. Under the chosen conditions,
      the peak currents are correspondent linearly to the concentrations of DA in the
      range of 5 x 10(-7) approximately 4 x 10(-4) mol L(-1) with a limit of detection
      of 2 x 10(-7) mol L(-1). The proposed method can be applied to detect DA in real
      samples.

PMID- 15950548
TI  - Glucose metabolism and Alzheimer's disease.
AB  - The brain is the organ with the highest basal rate of glucose consumption. Most
      of the energy generated by the oxidation of glucose is used for the work
      necessary to maintain the ionic balances associated with synaptic transmission.
      When the nervous system is subjected to the oxidative stress of age-associated
      disease, there is a redistribution of glucose breakdown to pathways that more
      efficiently produce molecules involved in antioxidant metabolism. This shift is
      at least in part mediated by the transcription factor HIF-1. The clinical
      implications of this change in glucose metabolism are discussed in the context of
      aging and Alzheimer's disease.

PMID- 15950549
TI  - Histone acetylation, chromatin remodelling, transcription and nucleotide excision
      repair in S. cerevisiae: studies with two model genes.
AB  - We describe the technology and two model systems in yeast designed to study
      nucleotide excision repair (NER) in relation to transcription and chromatin
      modifications. We employed the MFA2 and MET16 genes as models. How transcription
      coupled (TCR) and global genome repair (GGR) operate at the transcriptionally
      active and/or repressed S. cerevisiae MFA2 locus, and how this relates to
      nucleosome positioning are considered. We discuss the role of the Gcn5p histone
      acetyltransferase, also associated with MFA2's transcriptional activation, in
      facilitating efficient NER at the transcriptionally active and inactive genes.
      The effect of Gcn5p's absence in reducing NER was local and UV stimulates Gcn5p
      mediated histone acetylation at the repressed MFA2 promoter. After UV irradiation
      Swi2p is partly responsible for facilitating access to restriction of DNA in the
      cores of the nucleosomes at the MFA2 promoter. The data suggest similarities
      between chromatin remodelling for NER and transcription, yet differences must
      exist to ensure this gene remains repressed in alpha cells during NER. For MET16,
      we consider experiments examining chromatin structure, transcription and repair
      in wild type and cbf1Delta cells under repressing or derepressing conditions.
      Cbf1p is a sequence specific DNA binding protein required for MET16 chromatin
      remodelling and transcription.

PMID- 15950550
TI  - REV1 mediated mutagenesis in base excision repair deficient mouse fibroblast.
AB  - The DNA polymerase beta (Pol beta) null background renders mouse embryonic
      fibroblast (MEF) cells base excision repair deficient and hyper-mutagenic upon
      treatment with the monofunctional alkylating agent, methyl methanesulfonate
      (MMS). This effect involves an increase in all types of base substitutions, with
      a modest predominance of G to A transitions. In the present study, we examined
      the hypothesis that the MMS-induced mutagenesis in the Pol beta null MEF system
      is due to a lesion bypass mechanism. We studied the effect of RNAi mediated down
      regulation of the lesion bypass factor REV1. The steady-state level of REV1
      protein was reduced by more than 95% using stable expression of a siRNA construct
      in a Pol beta null cell line. We found that REV1 expression is required for the
      MMS-induced mutagenesis phenotype of Pol beta null MEF cells. In contrast, cell
      survival after MMS treatment is not reduced in the absence of REV1.

PMID- 15950551
TI  - Repair of the three main types of bipyrimidine DNA photoproducts in human
      keratinocytes exposed to UVB and UVA radiations.
AB  - Induction of DNA damage by solar UV radiation is a key event in the development
      of skin cancers. Bipyrimidine photoproducts, including cyclobutane pyrimidine
      dimers (CPDs), (6-4) photoproducts (64 PPs) and their Dewar valence isomers, have
      been identified as major UV-induced DNA lesions. In order to identify the
      predominant and most persistent lesions, we studied the repair of the three types
      of photolesions in primary cultures of human keratinocytes. Specific and
      quantitative data were obtained using HPLC associated with tandem mass
      spectrometry. As shown in other cell types, 64 PPs are removed from UVB
      irradiated keratinocytes much more efficiently than CPDs. In contrast, CPDs are
      still present in high amounts when cells recover their proliferation capacities
      after cell cycle arrest and elimination of a part of the population by apoptosis.
      The predominance of CPDs is still maintained when keratinocytes are exposed to a
      combination of UVB and UVA. Under these conditions, 64 PPs are converted into
      their Dewar valence isomers that are as efficiently repaired as their (6-4)
      precursors. Exposure of cells to pure UVA radiation generates thymine cyclobutane
      dimers that are slightly less efficiently repaired than CPDs produced upon UVB
      irradiation. Altogether, our results show that CPDs are the most frequent and the
      less efficiently repaired bipyrimidine photoproducts irrespectively of the
      applied UV treatment.

PMID- 15950552
TI  - The interface between measurement and modeling of peripheral lung mechanics.
AB  - The mechanical properties of the lung periphery are vital to the overall function
      of the whole organ, and play a key role in the symptomatology of many lung
      diseases. We first review the experimental methodologies that have been used to
      investigate peripheral lung mechanics, including the retrograde catheter, the
      alveolar capsule, the alveolar capsule oscillator, and the forced oscillation
      technique. We then discuss the interpretation of the data provided by these
      techniques in terms of inverse mathematical models of the lung, including the
      constant-phase model. Finally, we describe efforts to construct anatomically
      accurate forward models of the lung based on data from imaging modalities such as
      computed tomography and magnetic resonance imaging. Together, these various
      approaches have provided a great deal of information about the relative
      importance of the lung periphery in mechanical function in animal models of lung
      disease and in human patients. An increasing body of evidence indicates that
      constriction in this part of the lung is a crucial determinant of the severity of
      asthma.

PMID- 15950553
TI  - Effects of methacholine on small airway function measured by forced oscillation
      technique and multiple breath nitrogen washout in normal subjects.
AB  - The multiple breath nitrogen washout (MBNW) can be analysed to produce the
      parameters Scond and Sacin as measures of ventilation heterogeneity in conductive
      and acinar airways, respectively. The derivation of these parameters is based on
      a model of pulmonary ventilation and results of similar modelling suggest that
      respiratory system conductance (Grs) measured by forced oscillation technique
      (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond,
      the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related
      parameters. These relationships were examined in 12 normals under baseline and
      bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5=Grs5/FRC) and
      Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge.
      Scond was independently predicted by VtrappedFRC and FRC in a multivariate model
      (R2=0.68, p=0.002). Post methacholine challenge, Scond related only to
      VtrappedFRC (R2=0.79, p<0.0001). The absolute change in Scond induced by
      methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in
      a multivariate model (R2=0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and
      sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are
      measurements that are sensitive to changes occurring to the function of
      peripheral conducting airways, in particular heterogeneity and airway closure,
      while Sacin and presumably heterogeneity in terminal airways, are independent of
      these. Scond is also related to lung size. We review the current state of
      knowledge of FOT and MBNW in obstructive lung diseases and discuss future
      research directions.

PMID- 15950554
TI  - Maturational changes in neuromodulation of central pathways underlying hypoxic
      ventilatory response.
AB  - The neuromodulator systems mediating the central component of the hypoxic
      ventilatory response (HVR) during development are complex and diverse. The early
      component of the HVR is mediated through N-methyl-D-aspartate (NMDA) glutamate
      receptors in the caudal brainstem. The intracellular downstream signal
      transductions of the NMDA receptors involve protein kinase C (PKC), neuronal
      nitric oxide synthase (nNOS) and tyrosine kinase (TK). Activation of NMDA
      receptors will also lead to activation of the early gene transcription factors
      including AP-1 (c-fos, c-jun) and NF-kappaB which may play a role in modulation
      of the subsequent response to hypoxia. NMDA receptors in the caudal brainstem
      play a critical role in the development of the HVR and increasing dependency on
      NMDA receptors emerges over time. Similarly, hypoxia-induced PKC, NOS and c-Fos
      activation in the caudal brainstem is relatively weak in the immature animals,
      but this activation increases with age and the strength of the response appears
      to increase concomitantly with the appearance of NMDA expression. Several
      neurotransmitters including adenosine, gamma-aminobutyric acid (GABA), serotonin
      and opioids are involved in the late component of the HVR. In addition, the late
      phase of the HVR is mediated in part through platelet-derived growth factor
      (PDGF)-beta receptors. PDGF-beta receptor activation is an important contributor
      of the hypoxic ventilatory depression at all postnatal ages, but its role is more
      critical in the developing animals. Maturation of these neuromodulators,
      especially the NMDA and PDGF-beta receptors-mediated pathways, occurs primarily
      during the early postnatal period. Perturbation of these developmental processes
      may result in short-term or sustained alterations to the HVR and may also affect
      neuronal survival during hypoxia.

PMID- 15950555
TI  - HPLC analysis of PAMAM dendrimer based multifunctional devices.
AB  - Comprehensive high-performance liquid chromatography (HPLC) analyses were
      performed on poly(amidoamine) (PAMAM) dendrimer based multifunctional devices.
      The nanometer-size devices were synthesized by conjugating partially acetylated
      (Ac) poly(amidoamine) dendrimers of generation 5 (G5) with fluorescein
      isothiocyanate (FITC), folic acid (FA) and methotrexate (MTX). The devices are
      intended for targeted intracellular drug delivery to tumor cells through the
      folate receptor. Methods were developed for detection and separation of various
      surface functionalized dendrimer conjugates and small molecules (FITC, FA, MTX)
      using a common gradient. Results indicate that the HPLC technique can be used as
      a quality control tool for determining purity of the G5 carrier, its acetylated
      form, and mono-, bi- and tri-functional nanodevices. More importantly, the
      chromatograms of these novel nanodevices, reported for the first time, provide
      information on critical properties such as polydispersity, surface heterogeneity
      and solubility. The benchmark data can be used to optimize the physicochemical
      properties of the conjugates to improve drug delivery to cancer cells.

PMID- 15950556
TI  - The biological standard of living in 19th century Mexico and in the American
      West.
AB  - During the mid-19th century, the United States acquired Texas and large parts of
      Mexican territory with the vast Mexican-born population. This paper considers the
      biological standard of living of the part of this population that was
      incarcerated in American prisons. We use their physical stature as a proxy for
      their biological welfare. These data confirm earlier results which showed that
      adult heights tended to stagnate in Mexico during the late-19th century despite
      considerable social and political turmoil. While there is some evidence of a
      decline in height among youth, the decline is slight (<1 cm). As in other 19th
      century samples, farmers were the tallest. Americans were taller than Mexican
      prisoners by about 2 cm.

PMID- 15950557
TI  - Functions for proteinases in the ovulatory process.
AB  - The ovary is a unique and dynamic organ in respect to rapid and extensive degrees
      of tissue development and remodeling that are periodically repeated in the female
      reproductive activity. Ovulation is a directed and sequential process accompanied
      by broad-spectrum proteolysis and culminates in the follicular rupture to release
      the matured oocyte. This review will focus on the potential roles of six
      representative proteinases that are involved in various aspects of ovulatory
      processes: matrix metalloproteinases (MMPs), plasminogen activator (PA)/plasmin,
      a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS),
      cathepsin-L, pregnancy-associated plasma protein-A (PAPP-A), and bone
      morphogenetic protein 1/mammalian Tolloid (BMP-1/mTld). Based on the studies of
      expression and function, these selected proteinases provide and share diverse
      functions ranging from cleaving components of the extracellular matrix (ECM) to
      modulating non-ECM molecules, such as various growth factors and their binding
      proteins. Consistently, the genetic deletion of each individual gene in mice
      shows their functional overlap in the reproductive activity.

PMID- 15950558
TI  - Relation between homocysteine and B-vitamin status indicators and bone mineral
      density in older Americans.
AB  - Recent studies have found a connection between hyperhomocysteinemia and hip
      fracture. If this association is causal, it could be mediated through detrimental
      effects of low B-vitamin status on bone mineral density (BMD). Studies have
      linked homocysteine (Hcy) and the established Hcy determinants folate and vitamin
      B12, to BMD, but results have been inconsistent. Furthermore, only one study
      considered the specific marker of tissue vitamin B12 status, methylmalonic acid
      (MMA), and none have considered red blood cell (RBC) folate. To further explore
      associations between Hcy and B-vitamin status indicators and bone health, we used
      data collected on older (i.e., aged >55 years) men and women who underwent DEXA
      scans of the hip as participants in phase 2 of the third U.S. National Health and
      Nutrition Examination Survey (n = 1550). We used BMD at the total hip as a
      continuous outcome variable in some analyses. In others, we used osteoporosis
      defined on a sex- and race/ethnicity-specific basis according to World Health
      Organization (WHO) guidelines. After adjusting for demographic factors, body mass
      index, and other osteoporosis risk factors, BMD decreased and osteoporosis
      increased significantly with increasing serum MMA quartile category (P < 0.01).
      Serum vitamin B12 was related to BMD in dose-response fashion up to about 200
      pmol/L, and subjects with serum Hcy > or = 20 micromol/L had significantly lower
      BMD than subjects with serum Hcy < 10 micromol/L. Furthermore, the OR (95% CI)
      relating a serum vitamin B12 concentration below the 25th percentile to
      osteoporosis/osteopenia was 2.0 (1.0-3.9), and dose-response trends relating both
      serum B12 and Hcy to this outcome were marginally statistically significant.
      Neither serum nor RBC folate was related to BMD or osteoporosis. We conclude that
      Hcy and vitamin B12 status indicators are associated with BMD in older Americans.
      Whether this association reflects a causal relation remains unclear and merits
      further study in light of age-related declines in B12 status and BMD, and the
      need for low-risk, easily implemented strategies for osteoporosis prevention.

PMID- 15950559
TI  - Relation of timing of cardiac catheterization to outcomes in patients with non-ST
      segment elevation myocardial infarction or unstable angina pectoris enrolled in
      the multinational global registry of acute coronary events.
AB  - We assessed whether timing of catheterization is associated with the type of non
      ST-segment elevation acute coronary syndrome and/or outcome in patients who were
      enrolled in the Global Registry of Acute Coronary Events. Overall, 8,853 patients
      who had unstable angina pectoris or non-ST-elevation myocardial infarction were
      categorized according to timing of catheterization: expeditive (<24 hours), early
      (24 to 48 hours), and delayed (>48 hours). Patients in the delayed group were
      older, more frequently had previous myocardial infarction or stroke, and had a
      higher risk score compared with those in the expeditive and early groups (all p <
      or =0.001). Killip class IV at admission, non-ST-elevation myocardial infarction,
      and Q waves after the index electrocardiogram were more common in the expeditive
      group (all p <0.0001). Patients in the expeditive and early groups were treated
      more aggressively with medications than were those in the delayed group. The in
      hospital composite end point (death, stroke, or major bleed) occurred most
      frequently in the expeditive group (expeditive 6.6%, early 3.9%, delayed 5.1%, p
      = 0.0005), as did in-hospital death (expeditive 3.5%, early 1.4%, delayed 2.0%, p
      <0.0001). The highest incidence of death during follow-up occurred in the delayed
      group (3.8% delayed vs 2.8% expeditive/early, p = 0.0210). Multivariate
      regression analysis suggested that expeditive catheterization was related to in
      hospital death and death from time of catheterization to 6 months. We conclude
      that expeditive catheterization is associated with unstable presenting features
      that contribute significantly to the higher risk of death and death or myocardial
      infarction in hospital compared with patients who undergo later catheterization.

PMID- 15950560
TI  - Characterization of myocardial infarction as an end point in two large trials of
      acute coronary syndromes.
AB  - Myocardial infarction (MI) is a key component of composite end points in trials
      that evaluate new therapies in non-ST-segment elevation acute coronary syndromes.
      Types of MI events in these trials have not been well characterized. A similar
      clinical-events classification process adjudicated all suspected MI end points in
      the PURSUIT and PARAGON B trials. All MI end points were classified as
      nonprocedural, related to percutaneous coronary intervention, or related to
      coronary artery bypass grafting. A total of 16,173 patients was enrolled in the 2
      trials, and 1,802 MI end points occurred during a 30-day follow-up. Nearly 66% of
      MI end points were not related to percutaneous coronary intervention or coronary
      artery bypass grafting. Patients who had MI compared with those who did not had
      higher 30-day mortality rates (13.6% vs 2.3%, p <0.001) and 6-month mortality
      rates (18.4% vs 4.4%, p <0.001). Patients who had been randomized to glycoprotein
      IIb/IIIa inhibition showed trends toward fewer MI events regardless of type. Two
      thirds of MI end points in 2 large trials of acute coronary syndrome were not
      related to procedure. All MI types were associated with worse short- and long
      term outcomes. Characterization of the type of MI provides an opportunity for
      more informed interpretation of clinical trial results and improved planning for
      future trials.

PMID- 15950561
TI  - Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents
      for percutaneous coronary intervention in patients at high risk for coronary
      restenosis or clinical adverse events.
AB  - We evaluated the clinical effect of selective use of sirolimus-eluting stents
      (SESs) in real-world, high-risk patients. A total of 4,237 consecutive patients
      who underwent percutaneous coronary intervention (SES, n = 872, bare metal stents
      [BMSs], n = 3,365) was enrolled in a prospective regional survey. A prespecified
      high-risk subset of patients was selected on the basis of clinical and
      angiographic characteristics. A propensity score analysis was performed to
      compare patients who received SESs with those who received BMSs. Patients in the
      SES group more often had diabetes and more frequently had previous myocardial
      infarction or coronary revascularization, type C lesions, and multivessel
      procedures. Patients who presented with acute myocardial infarction were treated
      more often with BMSs. At 9 months, the use of SESs was associated with fewer
      major adverse cardiac events (death, myocardial infarction, or target lesion
      revascularization; hazard ratio 0.56, 95% confidence interval 0.37 to 0.85) and
      target lesion revascularizations (hazard ratio 0.43, 95% confidence interval 0.20
      to 0.91). This decrease was more evident in a prespecified high-risk subgroup of
      patients (major adverse cardiac events, 8.0% SES vs 15.6% BMS, hazard ratio 0.45,
      95% confidence interval 0.29 to 0.72). We conclude that selective SES use in real
      world patients who have high-risk clinical and angiographic characteristics is
      associated with significant decreases in major adverse cardiac events and repeat
      revascularizations compared with BMS use.

PMID- 15950562
TI  - Morphometric analysis of particulate debris extracted by four different embolic
      protection devices from coronary arteries, aortocoronary saphenous vein conduits,
      and carotid arteries.
AB  - Different embolic protection devices have been introduced for endovascular
      interventions: filters or balloon occlusion and aspiration systems. Despite
      widening use in a variety of vascular beds and clinical syndromes, little is
      known about the particulate burden liberated from different vascular beds and
      caught by different protection devices. We performed histologic and morphometric
      analyses of particulate debris captured during stenting of degenerated saphenous
      vein bypass grafts and native coronary arteries during acute myocardial
      infarction or during elective intervention and carotid arteries to assess the
      relative performance of different protection devices. We analyzed 232
      interventions (90 saphenous vein bypass grafts, 77 native coronary arteries, and
      65 carotid arteries) with 4 different devices (65 FilterWires, 99 Interceptors,
      41 GuardWires, and 27 Proxis catheters) using the RapidVue particle analyzer. No
      difference in embolic volume retrieved was demonstrated between devices in
      saphenous vein bypass grafts and carotid interventions. A smaller volume of
      particulate debris was retrieved by the GuardWire compared with the FilterWire
      and the Proxis catheter in native coronary artery interventions. The Interceptor
      and the GuardWire captured more smaller particles than did the FilterWire or
      Proxis catheter. During saphenous vein bypass graft or carotid intervention,
      different embolic protection strategies were performed similarly. In native
      coronary artery stenting, however, proximal embolic protection retrieved larger
      amounts of debris than did distal filters or occlusion devices. These data may
      allow greater tailoring of embolic protection device development and application
      in specific anatomic locales.

PMID- 15950563
TI  - Family history, plasma homocysteine, and age at onset of symptoms of myocardial
      ischemia in patients with different methylenetetrahydrofolate reductase
      genotypes.
AB  - A high plasma homocysteine level is associated with early onset of coronary
      artery disease (CAD), particularly in homozygotes for the C677T mutation in the
      methylenetetrahydrofolate reductase (MTHFR) gene. Family history is a predictor
      of increased plasma homocysteine and may be involved in early-onset CAD. This
      study examined the relations among family history, plasma homocysteine, and age
      at onset of CAD, and the role of the MTHFR genotype in this context. We screened
      284 patients who developed first symptoms of CAD at < or =65 years of age for
      fasting plasma homocysteine and the C677T mutation. On multiple regression
      analysis, homocysteine, family history, male gender, and smoking were
      independently associated with age at onset of CAD. However, separate analysis of
      patients who had the MTHFR 677 T/T genotype (n = 57) and those who did not (n =
      209) showed that plasma homocysteine and family history were associated with
      earlier onset of CAD only in T/T homozygotes and that family history in patients
      who had this genotype was also associated with higher plasma homocysteine levels
      and a stronger association between plasma homocysteine and age at onset of CAD.
      In patients who had other genotypes, these associations were not observed, and
      earlier onset of CAD was associated only with male gender and smoking. Thus, the
      MTHFR genotype modifies the effects of family history and other risk factors on
      age at onset of CAD. In T/T homozygotes, family history is associated with
      earlier onset of CAD, higher plasma homocysteine levels, and a stronger
      association between plasma homocysteine and age at onset of CAD.

PMID- 15950564
TI  - Electrophysiologic characteristics of verapamil-sensitive atrial tachycardia
      originating from the atrioventricular annulus.
AB  - We examined the electrophysiologic characteristics and mechanisms of verapamil
      sensitive atrial tachycardia (AT) originating from the atrioventricular (AV)
      annulus in 18 patients. AT originated from the AV node vicinity (AV nodal AT, 10
      patients) and the area distant from the AV node (non-AV nodal AT, 8 patients).
      There was no significant difference in the tachycardia cycle length between AV
      nodal and non-AV nodal AT. For both types of AT, tachycardia was inducible by
      atrial extrastimulation with an inverse relation between the coupling and the
      postpacing intervals. A single extrastimulus delivered from the earliest atrial
      activation site reset both ATs with an inverse relation between the coupling
      interval and return cycle. Also no significant difference was observed in the
      percentage of the excitable gap to tachycardia cycle length between AV nodal and
      non-AV nodal AT. Concealed entrainment was observed by rapid atrial pacing
      delivered from the earliest atrial activation site for both ATs. These findings
      suggest that these ATs are due to reentry. Intravenous administration of
      verapamil (2.5 to 5 mg) and adenosine triphosphate (5 mg) terminated AT in all
      patients. AT was successfully ablated at the earliest atrial activation site in
      all patients. It was shown that this form of AT in which a calcium channel
      dependent substrate is involved arises not only from the vicinity of the AV node
      but also along the AV annulus with common electrophysiologic characteristics.
      These suggest the presence of a distinct entity of tachycardia more appropriately
      classified as verapamil-sensitive AV annular AT.

PMID- 15950565
TI  - A comparison of the AVID and DAVID trials of implantable defibrillators.
AB  - We compared 2 studies of implantable cardiac defibrillators (ICDs) to determine
      the effects of device mode on outcomes. The Antiarrhythmics Versus Implantable
      Defibrillators (AVID) trial (1993 to 1997) demonstrated improved survival with
      the ICD compared with antiarrhythmic drug therapy. The Dual-chamber And VVI
      Implantable Defibrillator (DAVID) trial (2000 to 2002) showed that VVI pacing at
      40 beats/min in patients with ICDs reduced the combined end point of death and
      hospitalization for congestive heart failure compared with DDDR pacing at 70
      beats/min. Patients in the AVID trial (631 of 1,016) and the DAVID trial (221 of
      506) meeting common inclusion and all exclusion criteria were studied. The major
      end points were the time to death, and the composite end point of time to death
      or hospitalization for congestive heart failure. Patients in the AVID and DAVID
      trials were similar, but more AVID patients had coronary artery disease (p =
      0.04), history of myocardial infarction (p = 0.005), and previous ventricular
      arrhythmias (p = 0.03). DAVID patients underwent more previous revascularization
      procedures (coronary artery bypass surgery, p = 0.03; percutaneous coronary
      intervention, p = 0.001), and were more often taking beta-blocking drugs at
      hospital discharge (p <0.001). The backup VVI ICD groups in both studies had
      similar outcomes (p = 0.4), even when corrected for the previous demographic
      differences. The time-to- composite end point was similar in AVID patients
      treated with antiarrhythmic drugs and DAVID patients treated with DDDR ICDs (p =
      0.6). Despite improved pharmacologic therapy and revascularization, outcomes have
      not improved with backup VVI pacing ICDs. If DDDR ICDs had been used in the AVID
      trial, benefit from ICDs for patients with serious ventricular arrhythmias could
      have been missed.

PMID- 15950566
TI  - Predictors of lack of response to resynchronization therapy.
AB  - About 30% of patients treated with cardiac resynchronization therapy (CRT) do not
      respond to treatment. The aim of this study was to identify clinical predictors
      of lack of improvement in patients receiving CRT. From 197 consecutive patients
      scheduled to receive CRT, 143 fulfilled the inclusion criteria. Mean age was 68
      +/- 7 years and 79% were men. Heart failure was due to ischemic heart disease in
      49 patients (34%). Mean QRS duration was 165 +/- 26 ms, and left ventricular
      ejection fraction was 27 +/- 7%. Nonresponder patients were defined as those who
      died of heart failure, underwent heart transplantation, or did not increase the
      distance walked in 6 minutes >10%. At 6-month follow-up, there were 28
      nonresponders (20%). Among nonresponders, 2 patients received a heart
      transplantation and 9 patients died of heart failure. In logistic regression
      analysis, independent predictors of lack of response to CRT were ischemic heart
      disease (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.2 to 7; p = 0.023),
      severe mitral regurgitation (OR 3.5, 95% CI 1.3 to 9; p = 0.014), and left
      ventricular end-diastolic diameter > or =75 mm (OR 3.1, 95% CI 1.1 to 8; p =
      0.026). Patients with these 3 predictors had a probability response of 27%.

PMID- 15950568
TI  - Usefulness of atrial size inequality as an indicator of abnormal left ventricular
      filling.
AB  - Although pulsed Doppler echocardiography estimates current left ventricular (LV)
      filling, left atrial (LA) size reflects LV filling and pressure over time.
      However, the wide normal LA size range may blunt this diagnostic tool. Our
      objective was to compare the intraindividual atrial area difference (LA--right
      atrial [RA] area) and absolute LA area in their detection of a LA enlargement
      with respect to the degree of current LV filling impairment. We examined patients
      with acute coronary syndromes in sinus rhythm and without valvular disease (n =
      154), and age- and gender-matched healthy controls (n=50) with echocardiography,
      applying pulsed Doppler international recommendations to group the patients
      according to the LV filling pattern: 0, normal; 1, delayed relaxation; 2, an
      isolated abnormal mitral pulmonary venous A-wave duration difference; 3,
      pseudonormal; and 4, restrictive. The LA and RA areas were measured in the 4
      chamber view. Control values defined the normal range of: absolute LA area, LA
      area adjusted for body height, and LA-RA area. These areas indicated a LA
      enlargement in: (1) controls, 2%, 2%, and 4%, respectively; (2) patients with LV
      filling graded as normal/mildly impaired (groups 0 and 1), 15%, 17%, and 46%,
      respectively; moderately impaired (group 2), 26%, 29%, and 52%, respectively; and
      severely impaired (group 3 and 4), 42%, 38%, and 54%, respectively. Unequally
      sized atria appear to detect LA enlargement sensitively, especially when Doppler
      evidence of LV filling pathology is sparse. Clinically, with no obvious current
      cause for LA enlargement, a diagnosed "atrial size inequality" may still indicate
      a history of such causes.

PMID- 15950567
TI  - Valvular heart disease as a cause of cerebrovascular disease in patients with
      systemic lupus erythematosus.
AB  - Thirty-seven patients with systemic lupus erythematosus underwent complete
      clinical and laboratory evaluations, including antiphospholipid antibodies and
      lupus anticoagulant, magnetic resonance imaging of the brain, and transesophageal
      echocardiography. Cerebrovascular disease manifested as stroke, transient
      ischemic attack, or cerebral infarcts in patients with nonfocal neurologic
      deficits was detected in 19 patients (51%), and significant left-sided valvular
      heart disease in 25 (68%). Valve vegetations, valve thickening, valve
      regurgitation, and lupus anticoagulant antibody occurred 2 to 3 times more often
      in patients with than without cerebrovascular disease (all p < or =0.04) and were
      the only independent predictors of cerebrovascular disease (odd ratios 5.3 to
      10.6, all p < or =0.03). Thus, valvular heart disease probably exacerbated by
      hypercoagulability appears to be a source of embolic ischemic brain injury and
      cerebrovascular disease.

PMID- 15950569
TI  - Inhibition of platelet aggregation with eptifibatide, bivalirudin, and heparin in
      patients undergoing percutaneous coronary intervention receiving clopidogrel
      pretreatment (The PharmacoDynamic Evaluation of Angiomax, Clopidogrel with or
      without INtegrilin [DEACON] study).
AB  - The present study assessed the magnitude of inhibition of platelet aggregation
      induced by adenosine diphosphate and thrombin receptor activating peptide
      achieved with unfractionated heparin, the direct thrombin inhibitor bivalirudin,
      and the glycoprotein IIb/IIIa inhibitor eptifibatide in patients who underwent
      percutaneous coronary intervention and and were treated with concomitant aspirin
      and clopidogrel.

PMID- 15950570
TI  - Longevity of the placebo effect in the therapeutic angiogenesis and laser
      myocardial revascularization trials in patients with coronary heart disease.
AB  - The long-term beneficial effects of placebo therapy were evaluated in
      angiogenesis and laser myocardial revascularization trials in patients who had
      end-stage coronary heart disease. Improvements in mean angina class, exercise
      treadmill time, and quality of life were mostly maintained at 30 +/- 6 months of
      follow-up. Persistence of effect cannot be used as evidence of efficacy, and
      double-blinded trials are essential in this patient population.

PMID- 15950571
TI  - Absence of seasonal variation in myocardial perfusion, enzymatic infarct size,
      and mortality in patients with ST-segment elevation myocardial infarction treated
      with primary angioplasty.
AB  - The present study investigated any seasonal variation in myocardial perfusion,
      enzymatic infarct size, and 1-year mortality in 1,548 patients who underwent
      primary angioplasty for ST-segment elevation myocardial infarction. No seasonal
      variation was observed in patients' demographic and clinical characteristics. No
      difference was observed in the prevalence of heart failure at presentation and in
      myocardial perfusion, enzymatic infarct size, and 1-year mortality.

PMID- 15950572
TI  - Success, safety, and mechanisms of failure of percutaneous coronary intervention
      for occlusive non-drug-eluting in-stent restenosis versus native artery total
      occlusion.
AB  - We compared the procedural success, mechanism of failure, and safety of
      percutaneous coronary intervention in 235 procedures for de novo chronic total
      occlusions with 78 procedures for chronic occlusive in-stent restenosis. Despite
      similar rates of procedural success and safety profile, angiographic predictors
      of successful percutaneous coronary intervention for de novo chronic total
      occlusions played a limited role in patients who had chronic occlusive in-stent
      restenosis, and the mechanisms of failure were different.

PMID- 15950573
TI  - Validation of predictors of intraprocedural stent thrombosis in the drug-eluting
      stent era.
AB  - Although predictors of acute intraprocedural stent thrombosis (IPST) in the drug
      eluting stent era have been proposed, external validation is lacking. We thus
      analyzed the occurrence of IPST in the RECIPE study and found that, among 1,320
      patients who underwent drug-eluting stent implantation, IPST occurred in 6
      (0.5%), with in-hospital major adverse events in 4 (67%). IPST was predicted by
      number and total length of implanted stents, baseline minimal lumen diameter,
      and, in a pooled analysis that incorporated values from the present study and a
      previous study, use of elective glycoprotein IIb/IIIa inhibitors. Such results
      may provide useful information to guide prevention of this complication.

PMID- 15950574
TI  - Risk of thrombosis with the use of sirolimus-eluting stents for percutaneous
      coronary intervention (from registry and clinical trial data).
AB  - We conducted a meta-analysis on 6 studies in 2,963 patients who had coronary
      artery disease and received a sirolimus-eluting stent or a bare metal stent for
      revascularization. Compared with bare metal stents, sirolimus-eluting stents did
      not appear to increase the risk for thrombosis up to 13.5 months after coronary
      intervention (risk ratio 0.49, 95% confidence interval 0.22 to 1.12, p = 0.09).

PMID- 15950575
TI  - Prevalence of silent myocardial ischemia in persons with diabetes mellitus or
      impaired glucose tolerance and association of hemoglobin A1c with prevalence of
      silent myocardial ischemia.
AB  - Silent myocardial ischemia detected by exercise treadmill or pharmacologic
      sestamibi stress testing was present in 67 of 196 patients (34%) who had diabetes
      mellitus or impaired glucose tolerance and in 89 of 640 patients (14%) who had
      normal glucose tolerance (p <0.001). Among those who had diabetes mellitus or
      impaired glucose tolerance, silent myocardial ischemia was present in 27 of 54
      patients (50%) who had a hemoglobin A1c level > or =7.6% and in 39 of 137
      patients (28%) with a hemoglobin A1c level <7.6% (p <0.005).

PMID- 15950576
TI  - Relation of anemia to low heart rate variability in patients with coronary heart
      disease (from the Heart and Soul study).
AB  - We examined the association between anemia (hemoglobin < or =12 g/dl) and 6
      indexes of heart rate variability (HRV) as measured by 24-hour ambulatory
      electrocardiography in a cross-sectional study of 874 outpatients who had stable
      coronary heart disease. Of 90 participants who had anemia, 29% to 41% had low
      HRV, defined as the lowest quartile of each HRV index, compared with 23% to 25%
      of the 784 participants who did not have anemia (comparison p values <0.05 for
      all HRV indexes except high-frequency power). With the exception of high
      frequency power, each 1 g/dl decrease in hemoglobin was associated with increased
      odds of having low HRV. This association remained strong after adjustment for
      potential confounding variables, including ischemia, left ventricular mass, left
      ventricular ejection fraction, and diastolic dysfunction. Thus, anemia is
      associated with low HRV in ambulatory patients who have stable coronary heart
      disease. Low HRV could potentially mediate the association of anemia with
      increased cardiac risk.

PMID- 15950577
TI  - Brachial artery flow-mediated dilation and myocardial perfusion in patients with
      cardiac syndrome X.
AB  - We assessed the relation between systemic endothelial dysfunction abnormalities
      (brachial artery flow-mediated dilation) and myocardial perfusion abnormalities
      (single-photon emission computed tomography) in 41 patients who had cardiac
      syndrome X. Eighteen patients had normal perfusion scans and 18 had transient
      perfusion defects. Reverse redistribution was found in 5 patients. Patients who
      had myocardial perfusion defects had significantly lower flow-mediated dilation
      values (1.8%) than patients who had normal single-photon emission computed
      tomograms (3.9%, p = 0.012). Preserved systemic endothelial function appears to
      rule out the occurrence of transient single-photon emission computed tomographic
      defects in patients who have cardiac syndrome X.

PMID- 15950578
TI  - Effect of splitting simvastatin tablets for control of low-density lipoprotein
      cholesterol.
AB  - The efficacy, safety, and economics of a voluntary conversion from whole
      simvastatin tablets to split tablets in 6 Veterans Affairs medical centers were
      retrospectively evaluated in 3,787 patients who received a consistent daily dose
      (5 to 40 mg) of simvastatin in 1999. Baseline and final low-density lipoprotein
      cholesterol levels and average change from baseline were not significantly
      different between groups (p >0.05), nor were the incidence of transaminase
      increases (p >0.05) or measurements of patient compliance (p = 0.07). Widespread
      implementation of this initiative resulted in a cost avoidance of >$1.2 million
      in the 6 medical centers and $10.3 million across the Veterans Affairs medical
      system in 1999, with >$46 million avoided in 2003.

PMID- 15950579
TI  - Effectiveness of automated external defibrillators in high schools in greater
      Boston.
AB  - A program using a strategy of donating a single automatic external defibrillator
      to 35 schools in the Boston area resulted in compliance with American Heart
      Association guidelines on automatic external defibrillator placement and training
      and 2 successful resuscitations from sudden cardiac arrest. Participating schools
      indicated a high degree of satisfaction with the program.

PMID- 15950580
TI  - Implantable cardioverter-defibrillator efficacy in patients with heart failure
      and left ventricular dysfunction (from the MADIT II population).
AB  - The Multicenter Automatic Defibrillator Implantation Trial II demonstrated a
      significant 31% reduction in the risk of mortality in postinfarction patients
      with low ejection fraction (EF < or =30%). Recently, results from the Sudden
      Death in Heart Failure Trial indicated that a subgroup of patients with New York
      Heart Association (NYHA) class III heart failure had less benefit from an
      implantable cardioverter-defibrillator (ICD) than patients with less advanced
      heart failure. This study evaluates the association between NYHA class, EF, and
      blood urea nitrogen (BUN) levels as measures of heart failure and left
      ventricular dysfunction, and ICD benefit in reducing mortality as well as the
      association of these parameters with ICD therapy for ventricular
      tachyarrhythmias. NYHA class I was identified in 442 patients (36%), class II in
      425 (35%), and class III in 350 patients (29%). EF < or =20% was present in 472
      patients (38%), EF of 21% to 25% in 359 patients (29%), and EF of 26% to 30% in
      401 patients (33%). BUN < or =25 mg/dl was present in 850 patients (70%) and >25
      mg/dl in 368 patients (30%). Patients with higher NYHA class and BUN had higher
      mortality (34%) and a higher risk of arrhythmic events (33% to 35%) than patients
      in lower functional groups (16% to 20%). EF did not differentiate the risk. There
      was no evidence for significant interactions between mortality, ICD therapy, and
      tested parameters. In conclusion, patients with more advanced heart failure have
      a higher risk of mortality and arrhythmic events than patients with less severe
      disease. However, there is no significant difference in the benefit from ICD
      therapy among the above subgroups of patients in the Multicenter Automatic
      Defibrillator Implantation Trial.

PMID- 15950581
TI  - Usefulness of relative lymphocyte count as an independent predictor of
      death/urgent transplant in heart failure.
AB  - The usefulness of low relative lymphocyte count as an independent predictor of
      death/urgent transplant in patients with heart failure (HF) and the association
      between low relative lymphocyte count and neurohormone and cytokine activation
      were investigated. Relative lymphocyte count, clinical variables, neurohormones,
      and cytokines were measured in 129 outpatients with HF. Follow-up extended to a
      mean of 3.0 +/- 1.2 years for death/urgent transplant. Low relative lymphocyte
      count was independently associated with a 3.4-fold increased risk of death/urgent
      transplant. Relative lymphocyte count was positively associated with hemoglobin
      and inversely associated with age, jugular venous pressure, creatinine, leukocyte
      count, and soluble tumor necrosis factor receptor-1. There was only a borderline
      inverse association with cortisol levels during evening hours.

PMID- 15950582
TI  - Comparison of accuracy of mitral valve area in mitral stenosis by real-time,
      three-dimensional echocardiography versus two-dimensional echocardiography versus
      Doppler pressure half-time.
AB  - Mitral valve area (MVA) in 30 patients with mitral stenosis (MS) and 34 normal
      controls was calculated by real-time, 3-dimensional echocardiography (RT3DE); MVA
      in patients with MS correlated well with the mitral area determined by 2
      dimensional echocardiography (r = 0.98) and by pressure half-time (r = 0.90). MVA
      in normal controls on RT3DE correlated well with MVA on 2-dimensional
      echocardiography (r = 0.94) and pressure half-time (r = 0.91). There were
      significant differences between the orifice areas in patients with MS and normal
      controls. RT3DE can provide not only the anatomic structure of mitral valve
      apparatus, but also the optimal plane of the smallest mitral valve orifice, and
      can thus accurately measure the MVA.

PMID- 15950583
TI  - Early and late results of isolated and combined heart valve surgery in patients >
      or =80 years of age.
AB  - We present a series of 405 consecutive patients aged > or =80 years who underwent
      isolated or combined valve surgery over a 5-year period. Our results demonstrate
      that valve surgery in the elderly can be performed with acceptable early
      mortality, good late survival, and excellent late functional outcome.

PMID- 15950584
TI  - Long-term outcome of patients undergoing balloon mitral valvotomy in pregnancy.
AB  - The outcome of 36 patients (mean age 25.8 +/- 4.3 years) who underwent balloon
      mitral valvuloplasty during pregnancy is described in this report. The procedure
      was successful in 35 patients (97.2%), with no maternal mortality, and all
      patients subsequently had symptomatic improvement and uneventful deliveries. The
      children had normal growth and development at a follow up of 2.8 +/- 3.3 years.
      Thus, in patients with symptomatic severe mitral stenosis, balloon mitral
      valvuloplasty is feasible, safe, and effective with good long-term outcomes for
      both the mother and the fetus.

PMID- 15950585
TI  - Regional differences in systolic and diastolic function in arrhythmogenic right
      ventricular dysplasia/cardiomyopathy using magnetic resonance imaging.
AB  - Global and regional biventricular functions were analyzed in 14 patients
      diagnosed with arrhythmogenic right ventricular dysplasia/cardiomyopathy using
      cine magnetic resonance imaging and compared with similar data from 18 age
      matched controls. In this study, we report results of quantitative evaluation of
      biventricular global and regional function using peak ejection rate and peak
      filling rate as measures of systolic and diastolic function, respectively
      (volumetric method).

PMID- 15950587
TI  - Usefulness of branch pulmonary artery regurgitant fraction to estimate the
      relative right and left pulmonary vascular resistances in congenital heart
      disease.
AB  - In postoperative congenital heart patients with pulmonary regurgitation,
      individual branch pulmonary artery regurgitant fractions estimate relative
      pulmonary vascular resistance independent of pulmonary blood flow distribution.

PMID- 15950586
TI  - Effects of pulmonary valve replacement on QRS duration and right ventricular
      cavity size late after repair of right ventricular outflow tract obstruction.
AB  - This study evaluated the effects of pulmonary valve replacement (PVR) on QRS
      duration and right ventricular (RV) cavity size in patients who had severe
      pulmonary regurgitation late after previous repair of RV outflow tract
      obstruction. A significant decrease in maximal QRS duration and RV end-diastolic
      volume was found after PVR. The change in QRS duration was most significant in
      patients with a baseline QRS > or =155 ms (176 +/- 15 to 160 +/- 18 ms, p
      <0.001). RV end-diastolic volume was significantly correlated with maximal QRS
      duration before (r = 0.93, p <0.0001) as well as after (r = 0.82, p <0.001) PVR.
      In patients with pulmonary regurgitation late after repair of RV outflow tract
      obstruction, PVR reduces maximal QRS duration with a concomitant decrease in RV
      volumes.

PMID- 15950588
TI  - Transcatheter patch occlusion of perimembranous ventricular septal defects.
AB  - Sixteen surgical candidates for ventricular septal defect correction were brought
      to the catheterization laboratory for transcatheter patch occlusion. There were 3
      cases of nonrestrictive ventricular septal defects, including 2 with malalignment
      (tetralogy of Fallot). All patients, except those with tetralogy of Fallot who
      were cyanotic, had large left-right shunts. They were all corrected through the
      femoral vein. All defects with the exception of 2 were successfully occluded (12
      full occlusions, 2 residual shunts). On follow-up, there were no embolizations,
      aortic insufficiency, or other complications. The method appears effective and
      relatively safe, and could challenge the current surgical standard of treatment.

PMID- 15950589
TI  - Effects of weight loss after gastric bypass on right and left ventricular
      function assessed by tissue Doppler imaging.
AB  - To evaluate the effects of substantial weight loss on tissue Doppler imaging
      parameters of right ventricular (RV) and left ventricular (LV) systolic and
      diastolic function, we performed standard echocardiography and tissue Doppler
      imaging in 17 patients with severe obesity before and after gastric bypass.
      Patients lost 39 +/- 10 kg over 7.6 +/- 3.6 months. Adjusted LV mass decreased
      (134 +/- 41 to 119 +/- 31 kg/m, p = 0.031). After weight loss, the ratios of
      early-to-late diastolic mitral and tricuspid inflow velocities increased (1.3 +/-
      0.2 to 1.6 +/- 0.5, p = 0.02; 1.0 +/- 0.1 to 1.6 +/- 0.3, p = 0.003). Early
      diastolic tissue Doppler velocities increased at both the lateral and septal
      mitral annulus (7.6 +/- 1.5 to 9.3 +/- 2.5 cm/s, p = 0.009; and 6.6 +/- 1.4 to
      7.7 +/- 1.7 cm/s; p = 0.028, respectively) and for their 2-site average (7.2 +/-
      1.0 to 8.5 +/- 1.7 cm/s, p = 0.007). Early diastolic tricuspid annular velocity
      increased (7.2 +/- 2.8 to 10.6 +/- 2.3 cm/s, p <0.001) as did the ratio of early
      to-late tricuspid annular diastolic velocity (0.9 +/- 0.4 to 1.1 +/- 0.2, p =
      0.038). Tricuspid annular systolic velocity increased (8.6 +/- 2.5 to 10.3 +/-
      2.7 cm/s, p = 0.037). In patients with severe obesity, significant weight loss
      results in an increase in tricuspid annular systolic and early diastolic
      velocities and mitral annular early diastolic velocities.

PMID- 15950590
TI  - Trends in the incidence of pulmonary embolism and deep venous thrombosis in
      hospitalized patients.
AB  - Trends in the incidences of pulmonary embolism (PE), deep venous thrombosis
      (DVT), and venous thromboembolism (VTE) (PE or DVT, or both) in hospitalized
      adults (aged > or =20 years) were evaluated using data from the National Hospital
      Discharge Survey. From 1979 to 1999, the incidence of DVT in hospitalized
      patients increased from 0.8% of admissions to 1.3% of admissions. The incidence
      of PE was 0.4% of admissions and did not change over the 21-year period. Trends
      and incidences were similar or the same among men and women and whites and
      blacks.

PMID- 15950591
TI  - Prevalence of left ventricular diastolic dysfunction in obese persons with and
      without diabetes mellitus.
AB  - Forty obese diabetic patients (mean age 48 +/- 9 years) and 93 obese nondiabetic
      patients (mean age 43 +/- 9 years) underwent Doppler and tissue Doppler
      echocardiographic evaluation of left ventricular diastolic function before
      gastric bypass surgery. Moderate or severe left ventricular diastolic dysfunction
      was present in 24 of 40 obese diabetics (60%) and in 21 of 93 obese nondiabetics
      (23%) (p <0.001).

PMID- 15950592
TI  - Effectiveness of ulnar artery catheterization after failed attempt to cannulate a
      radial artery.
AB  - Transradial artery catheterization has become an accepted alternative approach to
      performing diagnostic and interventional coronary procedures. However, its
      usefulness can be limited by access site failure. We report on 12 patients in
      whom there was failure to cannulate the radial artery. Angiograms of the hand
      were performed on all patients through the ulnar sheath to determine the possible
      mechanism of failure to cannulate the radial artery and to determine the source
      of the blood supply to the hand. Irrespective of the mechanism of failure, each
      of the 12 procedures was subsequently successfully completed using the
      ipsilateral ulnar artery approach.

PMID- 15950593
TI  - Effect of selective cyclooxygenase-2 inhibitors on heart rate in healthy young
      men.
AB  - During an investigation of the possible pharmacokinetic interactions of
      cyclooxygenase-2 (COX-2) inhibitors with metoprolol, we observed that rofecoxib
      caused a significant reduction in heart rate in young healthy volunteers. The
      effect of valdecoxib did not reach significance. When these drugs were given
      together with metoprolol, the effect was continued. The latter effect could not
      be related to pharmacokinetic interactions. In the light of experimental results
      claiming a cardioprotective effect of possibly COX-2-derived prostaglandins and
      clinical observations hinting at an increased risk of sudden cardiovascular death
      in conjunction with the long-term use of selective cyclooxygenase inhibitors, our
      results may help to increase awareness and to suggest investigation of the impact
      of coxibs on heart function.

PMID- 15950594
TI  - Anticoagulation in patients with atrial fibrillation and congestive heart
      failure.

PMID- 15950595
TI  - Studies on canthaxanthin in lipid membranes.
AB  - Polar carotenoid pigment - canthaxanthin - has been found to interfere with the
      organization of biological membranes, in particular of the retina membranes of an
      eye of primates. The organization of lipid membranes formed with
      dipalmitoylphosphatidylcholine (DPPC) and egg yolk phosphatidylcholine containing
      canthaxanthin was studied by means of several techniques including: electronic
      absorption spectroscopy, linear dichroism, X-ray diffractometry, (1)H-NMR
      spectroscopy and FTIR spectroscopy. It appears that canthaxanthin present in the
      lipid membranes at relatively low concentration (below 1 mol% with respect to
      lipid) modifies significantly physical properties of the membranes. In
      particular, canthaxanthin (i) exerts restrictions to the segmental molecular
      motion of lipid molecules both in the headgroup region and in the hydrophobic
      core of the bilayer, (ii) promotes extended conformation of alkyl lipid chains,
      (iii) modifies the surface of the lipid membranes (in particular in the gel
      state, L(beta )) and promotes the aggregation of lipid vesicles. It is concluded
      that canthaxanthin incorporated into lipid membranes is distributed among two
      pools: one spanning the lipid bilayer roughly perpendicularly to the surface of
      the membrane and one parallel to the membrane, localized in the headgroup region.
      The population of the horizontal fraction increases with the increase in the
      concentration of the pigment in the lipid phase. Such a conclusion is supported
      by the linear dichroism analysis of the oriented lipid multibilayers containing
      canthaxanthin: The mean angle between the dipole transition moment and the axis
      normal to the plane of the membrane was determined as 20+/-3 degrees at 0.5 mol%
      and 47+/-3 degrees at 2 mol% canthaxanthin. The analysis of the absorption
      spectra of canthaxanthin in the lipid phase and (1)H-NMR spectra of lipids point
      to the exceptionally low aggregation threshold of the pigment in the membrane
      environment (approximately 1 mol%). All results demonstrate a very strong
      modifying effect of canthaxanthin with respect to the dynamic and structural
      properties of lipid membranes.

PMID- 15950596
TI  - Membrane insertion of betaine/GABA transporter during hypertonic stress
      correlates with nuclear accumulation of TonEBP.
AB  - MDCK cells stably transfected with betaine/GABA transporter tagged with EGFP
      (EGFP-BGT) were used to study plasma membrane insertion of EGFP-BGT. Adaptive
      response to hypertonicity requires nuclear migration of TonEBP. Confocal
      microscopy showed that after 6 h hypertonicity, the nuclear/cytoplasmic ratio of
      TonEBP fluorescence was increased to 2.4 compared to 1.4 in isotonic controls
      (P<0.001). The ratio in hypertonic cells was reduced by the proteasome inhibitor
      MG-132 in a dose-dependent way. Inhibition was 50% at 3 microM. After 6 h,
      hypertonicity expressed EGFP-BGT was localized in the plasma membrane, but there
      was no change in total EGFP-BGT abundance compared to isotonic controls. In
      contrast, EGFP-BGT remained mostly intracellular when 3 microM MG-132 was
      included in the hypertonic medium. The transport function of EGFP-BGT was studied
      as Na(+)-dependent uptake of [(3)H]GABA. This was not changed by MG-132 in
      isotonic controls, but MG-132 produced dose-dependent inhibition of hypertonic
      upregulation of Na(+)/GABA cotransport. Inhibition was 80% at 3 muM MG-132.
      Transport likely reflects membrane insertion of EGFP-BGT and there was a positive
      correlation (P<0.05) between Na(+)/GABA cotransport and the N/C ratio of TonEBP.
      Results are consistent with a role for TonEBP-mediated transcription in synthesis
      of additional proteins required for membrane insertion of EGFP-BGT protein.

PMID- 15950597
TI  - Characterization of the ion transport activity of the budding yeast Na+/H+
      antiporter, Nha1p, using isolated secretory vesicles.
AB  - The Saccharomyces cerevisiae Nha1p, a plasma membrane protein belonging to the
      monovalent cation/proton antiporter family, plays a key role in the salt
      tolerance and pH regulation of cells. We examined the molecular function of Nha1p
      by using secretory vesicles isolated from a temperature sensitive secretory
      mutant, sec4-2, in vitro. The isolated secretory vesicles contained newly
      synthesized Nha1p en route to the plasma membrane and showed antiporter activity
      exchanging H+ for monovalent alkali metal cations. An amino acid substitution in
      Nha1p (D266N, Asp-266 to Asn) almost completely abolished the Na+/H+ but not
      K+/H+ antiport activity, confirming the validity of this assay system as well as
      the functional importance of Asp-266, especially for selectivity of substrate
      cations. Nha1p catalyzes transport of Na+ and K+ with similar affinity (12.7 mM
      and 12.4 mM), and with lower affinity for Rb+ and Li+. Nha1p activity is
      associated with a net charge movement across the membrane, transporting more
      protons per single sodium ion (i.e., electrogenic). This feature is similar to
      the bacterial Na+/H+ antiporters, whereas other known eukaryotic Na+/H+
      antiporters are electroneutral. The ion selectivity and the stoichiometry suggest
      a unique physiological role of Nha1p which is distinct from that of other known
      Na+/H+ antiporters.

PMID- 15950598
TI  - Tetanically released zinc inhibits hippocampal mossy fiber calcium, zinc and
      synaptic responses.
AB  - At the zinc-enriched mossy fiber synapses from hippocampal CA3 area, electrical
      or chemical stimulation evokes zinc release from glutamatergic synaptic vesicles
      that may cause different pre- or postsynaptic actions. Besides zinc that can be
      co-localized with glutamate and GABA, the mossy fibers contain a very high
      density of ATP-sensitive potassium channels that are activated by zinc. We have
      investigated the possibility that intensely released zinc inhibits presynaptic
      calcium changes and consequently zinc and glutamate release. The studies were
      made combining optical recording of fast presynaptic calcium and zinc signals,
      using the fluorescent indicators Fura-2 and N-(6-methoxy-8-quinolyl)-para
      toluenesulfonamide, respectively, with measurements of field potentials. We have
      observed that strong tetanic stimulation caused posttetanic depressions of
      electrically induced presynaptic calcium and zinc signals and of synaptic
      responses, the depressions being blocked by zinc chelators. These results suggest
      that endogenously released zinc has an inhibitory role, mediated by presynaptic
      ATP-sensitive potassium channels and/or presynaptic calcium channels, that leads
      to the depression of zinc and glutamate release.

PMID- 15950599
TI  - Head, shoulders, knees, and toes.

PMID- 15950600
TI  - Asymmetric distribution of PAR proteins in the mouse embryo begins at the 8-cell
      stage during compaction.
AB  - In many organisms, like Caenorhabditis elegans and Drosophila melanogaster,
      establishment of spatial patterns and definition of cell fate are driven by the
      segregation of determinants in response to spatial cues, as early as oogenesis or
      fertilization. In these organisms, a family of conserved proteins, the PAR
      proteins, is involved in the asymmetric distribution of cytoplasmic determinants
      and in the control of asymmetric divisions. In the mouse embryo, it is only at
      the 8-cell stage during compaction that asymmetries, leading to cellular
      diversification and blastocyst morphogenesis, are first observed. However, it has
      been suggested that developmentally relevant asymmetries could be established
      already in the oocyte and during fertilization. This led us to study the PAR
      proteins during the early stages of mouse development. We observed that the
      homologues of the different members of the PAR/aPKC complex and PAR1 are
      expressed in the preimplantation mouse embryo. During the first embryonic
      cleavages, before compaction, PARD6b and EMK1 are observed on the spindle. The
      localization of these two proteins becomes asymmetric during compaction, when
      blastomeres flatten upon each other and polarize. PARD6b is targeted to the
      apical pole, whereas EMK1 is distributed along the baso-lateral domain. The
      targeting of EMK1 is dependent upon cell-cell interactions while the apical
      localization of PARD6b is independent of cell contacts. At the 16-cell stage,
      aPKCzeta colocalizes with PARD6b and a colocalization of the three proteins
      (PARD6b/PARD3/aPKCzeta can occur in blastocysts, only at tight junctions. This
      choreography suggests that proteins of the PAR family are involved in the setting
      up of blastomere polarity and blastocyst morphogenesis in the early mammalian
      embryo although the interactions between the different players differ from
      previously studied systems. Finally, they reinforce the idea that the first
      developmentally relevant asymmetries are set up during compaction.

PMID- 15950602
TI  - ABERRANT PANICLE ORGANIZATION 1 temporally regulates meristem identity in rice.
AB  - We report a recessive mutation of rice, aberrant panicle organization 1 (apo1),
      which severely affects inflorescence architecture, floral organ identity, and
      leaf production rate. In the wild-type inflorescence, the main-axis meristem
      aborts after forming 10-12 primary branch primordia. However, in apo1, the main
      axis meristem was converted to a spikelet meristem after producing a small number
      of branch primordia. In addition, the branch meristems in apo1 became spikelet
      meristems earlier than in wild type. Therefore, in the inflorescence, the apo1
      mutation caused the precocious conversion of the meristem identity. In the apo1
      flower, lodicules were increased at the expense of stamens, and carpels were
      formed indeterminately by the loss of meristem determinacy. Vegetative
      development is also affected in the apo1. Leaves were formed rapidly throughout
      the vegetative phase, indicating that APO1 is also involved in temporal
      regulation of leaf production. These phenotypes suggest that the APO1 plays an
      important role in the temporal regulation of both vegetative and reproductive
      development.

PMID- 15950601
TI  - Disruption in the tropomodulin1 (Tmod1) gene compromises cardiomyocyte
      development in murine embryonic stem cells by arresting myofibril maturation.
AB  - Tropomodulins (Tmods) comprise a family of capping proteins for actin filament
      pointed ends. To decipher the significance of Tmod1 functions during de novo
      myofibrillogenesis, we generated Tmod1 null embryonic stem (ES) cells and studied
      their differentiation into cardiomyocytes. Strikingly, in vitro cardiomyocyte
      differentiation of wild type (WT) ES cells faithfully recapitulates in vivo
      cardiomyocyte differentiation, allowing us to evaluate the phenotypes of Tmod1
      knockout (KO) myofibrils irrespective of embryonic lethality of Tmod1 KO mice.
      Immunofluorescence and electron microscopy studies revealed that Tmod1 null
      cardiac myocytes were round, morphologically immature, and contained
      underdeveloped myofibrils that were shorter, narrower, and had fewer thin
      filaments than those in WT cells. Unexpectedly, clear gaps in the staining
      pattern for F-actin at the H-zone were detected in most KO cells, indicating the
      presence of filaments at uniform lengths. This indicates that additional
      mechanisms other than capping proteins are responsible for thin filament length
      maintenance in cardiac myocytes. Also unexpectedly, approximately 40% of the KO
      cardiac myocytes exhibited contractile activity. Our data indicate that
      differentiating ES cells are a powerful system to investigate the functional
      properties of contractile proteins and that Tmod1 functions are critical for late
      stages of myofibrillogenesis, and for the maturation of myofibrils.

PMID- 15950603
TI  - Mouse cPLA2gamma, a novel oocyte and early embryo-abundant phospholipase A2 gamma
      like protein, is targeted to the nuclear envelope during germinal vesicle
      breakdown.
AB  - This report documents the characterization of a novel mouse oocyte protein which
      was originally identified by microsequence analysis of a 67.8 kDa protein spot
      (pI 5.7) on a Coomassie-stained two-dimensional (2D) gel of murine egg proteins.
      Tandem mass spectroscopic analysis of the peptides obtained from the cored
      protein yielded sequences that appeared to match only ovary, egg, and
      preimplantation embryo cDNAs. We then cloned the novel gene by RACE-PCR, and
      analysis of the deduced cDNA sequence found that this maternal product was
      approximately 56% identical to human cytosolic phospholipase A2gamma
      (cPLA2gamma). Based on this sequence homology, we named the molecule mouse
      cytosolic phospholipase A2gamma (cPLA2gamma). As with human cPLA2gamma, mouse
      cPLA2gamma contains a lipase consensus sequence and lacks the calcium binding
      domain that is found in other PLA2 proteins. However, mouse cPLA2gamma is
      different from human cPLA2gamma in that mouse cPLA2gamma expression is restricted
      to the ovary and that the protein does not contain the myristoylation and
      prenylation lipid-anchoring motifs that are present in human cPLA2gamma. Within
      oocytes, mouse cPLA2gamma localizes mainly to the oocyte cortex and to the
      nucleoplasm. Interestingly, during germinal vesicle breakdown, mouse cPLA2gamma
      aggregates dynamically relocate from the oocyte cortex to the nuclear envelope,
      suggesting a possible role for this putative egg-restricted phospholipase A2gamma
      in membrane remodeling. Furthermore, mouse cPLA2gamma protein continues to be
      expressed in the embryo until the 4-8-cell stage of development, suggesting that
      mouse cPLA2gamma may function as a previously uncharacterized maternal effect
      gene.

PMID- 15950604
TI  - Phenotypic analysis of EcR-A mutants suggests that EcR isoforms have unique
      functions during Drosophila development.
AB  - The steroid hormone ecdysone triggers transitions between developmental stages in
      Drosophila by acting through a heterodimer consisting of the EcR and USP nuclear
      receptors. The EcR gene encodes three protein isoforms (EcR-A, EcR-B1, and EcR
      B2) that have unique amino termini but that contain a common carboxy-terminal
      region including DNA-binding and ligand-binding domains. EcR-A and EcR-B1 are
      expressed in a spatially complementary pattern at the onset of metamorphosis,
      suggesting that specific responses to ecdysone involve distinct EcR isoforms.
      Here, we describe phenotypes of EcR-A specific deletion mutants isolated using
      transposon mutagenesis. Western blot analysis shows that each of these mutants
      completely lacks EcR-A protein, while the EcR-B1 protein is still present. The
      EcR(112) strain has a deletion of EcR-A specific non-coding and regulatory
      sequences but retains the coding exons, while the EcR(139) strain has a deletion
      of EcR-A specific protein coding exons but retains the regulatory region. In
      these mutants, the developmental progression of most internal tissues that
      normally express EcR-B1 is unaffected by the lack of EcR-A. Surprisingly,
      however, we found that one larval tissue, the salivary gland, fails to degenerate
      even though EcR-B1 is the predominant isoform. This result may indicate that the
      low levels of EcR-A in this tissue are in fact required. We identified yet
      another type of mutation, the EcR(94) deletion, that removes the EcR-A specific
      protein coding exons as well as the introns between the EcR-A and EcR-B
      transcription start sites. This deletion places the EcR-A regulatory region
      adjacent to the EcR-B transcription start site. While EcR(112) and EcR(139)
      mutant animals die during mid and late pupal development, respectively, EcR(94)
      mutants arrest prior to pupariation. EcR-A mutant phenotypes and lethal phases
      differ from those of EcR-B mutants, suggesting that the EcR isoforms have
      distinct developmental functions.

PMID- 15950605
TI  - Wnt signaling controls the timing of oligodendrocyte development in the spinal
      cord.
AB  - During spinal cord development, oligodendrocytes are generated from a restricted
      region of the ventral ventricular zone and then spread out into the entire spinal
      cord. These events are controlled by graded inductive and repressive signals
      derived from a local organizing center. Sonic hedgehog was identified as an
      essential ventral factor for oligodendrocyte lineage specification, whereas the
      dorsal cue was less clear. In this study, Wnt proteins were identified as the
      dorsal factors that directly inhibit oligodendrocyte development. Wnt signaling
      through a canonical beta-catenin pathway prevents its differentiation from
      progenitor to an immature state. Addition of rmFz-8/Fc, a Wnt antagonist,
      increased the number of immature oligodendrocytes in the spinal cord explant
      culture, demonstrating that endogenous Wnt signaling controls oligodendrocyte
      development.

PMID- 15950606
TI  - Slit/Robo signaling is necessary to confine early neural crest cells to the
      ventral migratory pathway in the trunk.
AB  - Neural crest cells migrate along two discrete pathways within the trunk of
      developing embryos. In the chick, early migrating crest cells are confined to a
      ventral pathway medial to the dermamyotome while later cells migrate on a dorsal
      pathway lateral to the dermamyotome. Here we show that Slits are expressed in the
      dermamyotome, that early migrating crest cells express the Slit receptors Robo 1
      and Robo 2, that Slit2 repels migrating crest cells in an in vitro assay, and
      that the misexpression of a dominant-negative Robo1 receptor induces a
      significant fraction of early crest cells to migrate ectopically in the dorso
      lateral pathway. These findings suggest that Slits, most likely those expressed
      in the dermamyotome, help to confine the migration of early crest cells to the
      ventral pathway.

PMID- 15950607
TI  - A novel function for the protein tyrosine phosphatase Shp2 during lung branching
      morphogenesis.
AB  - Branching morphogenesis of many organs, including the embryonic lung, is a
      dynamic process in which growth factor mediated tyrosine kinase receptor
      activation is required, but must be tightly regulated to direct ramifications of
      the terminal branches. However, the specific regulators that modulate growth
      factor signaling downstream of the tyrosine kinase receptor remain to be
      determined. Herein, we demonstrate for the first time an important function for
      the intracellular protein tyrosine phosphatase Shp2 in directing embryonic lung
      epithelial morphogenesis. We show that Shp2 is specifically expressed in
      embryonic lung epithelial buds, and that loss of function by the suppression of
      Shp2 mRNA expression results in a 53% reduction in branching morphogenesis.
      Furthermore, by intra-tracheal microinjection of a catalytically inactive
      adenoviral Shp2 construct, we provide direct evidence that the catalytic activity
      of Shp2 is required for proper embryonic lung branch formation. We demonstrate
      that Shp2 activity is required for FGF10 induced endodermal budding. Furthermore,
      a loss of Shp2 catalytic activity in the embryonic lung was associated with a
      reduction in ERK phosphorylation and epithelial cell proliferation. However,
      epithelial cell differentiation was not affected. Our results show that the
      protein tyrosine phosphatase Shp2 plays an essential role in modulating growth
      factor mediated tyrosine kinase receptor activation in early embryonic lung
      branching morphogenesis.

PMID- 15950608
TI  - New prestalk and prespore inducing signals in Dictyostelium.
AB  - The differentiation-inducing signals (DIFs) currently known in Dictyostelium
      appear unable to account for the full diversity of cell types produced in
      development. To search for new signals, we analyzed the differentiation in
      monolayers of cells expressing prestalk (ecmAO, ecmA, ecmO, ecmB and cAR2) and
      prespore (psA) markers. Expression of each marker drops off as the cell density
      is reduced, suggesting that cell interaction is required. Expression of each
      marker is inhibited by cerulenin, an inhibitor of polyketide synthesis, and can
      be restored by conditioned medium. However, the known stalk-inducing polyketide,
      DIF-1, could not replace conditioned medium and induce the ecmA or cAR2 prestalk
      markers, suggesting that they require different polyketide inducers. Polyketide
      production by fungi is stimulated by cadmium ions, which also dramatically
      stimulates differentiation in Dictyostelium cell cultures and the accumulation of
      medium factors. Factors produced with cadmium present were extracted from
      conditioned medium and fractionated by HPLC. A new factor inducing prespore cell
      differentiation, called PSI-2, and two inducing stalk cell differentiation (DIFs
      6 and 7) were resolved. All are distinct from currently identified factors. DIF
      6, but not DIF-7 or PSI-2, appears to have an essential carbonyl group. Thus
      Dictyostelium may use extensive polyketide signaling in its development.

PMID- 15950609
TI  - Temporal analysis of the early BMP functions identifies distinct anti-organizer
      and mesoderm patterning phases.
AB  - BMP signaling performs multiple important roles during early embryogenesis.
      Signaling through the BMP pathway is mediated by different BMP ligands expressed
      in partially overlapping temporal and spatial patterns. Assignment of different
      BMP-dependent activities to the individual ligands has relied on the patterns of
      expression of the various BMP genes. Temporal analysis of BMP signaling prior to
      and during gastrulation was performed using glucocorticoid-controlled Smad
      proteins. Overexpression of the BMP-specific Smad1 and Smad5 revealed that
      suppression of Spemann's organizer formation in Xenopus embryos can only take
      place by activating the BMP pathway prior to the onset of gastrulation. Blocking
      BMP signaling with the inhibitory Smad, Smad6, results in dorsalized embryos or
      secondary axis induction, only when activated up to early gastrula stages. BMP2
      efficiently represses organizer-specific transcription from the midblastula
      transition onwards while BMP4 is unable to prevent the early activation of
      organizer-specific genes. Manipulation of the BMP pathway during mid/late
      gastrula affects mesodermal patterning with no external phenotypic effects. These
      observations suggest that the malformations resulting from inhibition or
      promotion of organizer formation, ventralized or dorsalized, respectively, are
      the result of a very early BMP function, through its antagonism of organizer
      formation. This function is apparently fulfilled by BMP2 and only at its latest
      phase by BMP4. Subsequently, BMP functions in the patterning of the mesoderm with
      no apparent phenotypic effects.

PMID- 15950610
TI  - Radial leaves of the maize mutant ragged seedling2 retain dorsiventral anatomy.
AB  - ragged seedling2 (rgd2) is a novel, recessive mutation affecting lateral organ
      development in maize. The mutant phenotype of homozygous rgd2-R leaves is
      variable. Mild leaf phenotypes have a reduced midrib and may be moderately narrow
      and furcated; severe Rgd2-R(-) leaves are filamentous or even radial. Despite
      their radial morphology, severe Rgd2-R(-) mutant leaves develop distinct adaxial
      and abaxial anatomical features. Although Rgd2-R(-) mutants exhibit no reduction
      in adaxial or abaxial cell types, areas of epidermal cell swapping may occur that
      are associated with misaligned vascular bundles and outgrowths of ectopic
      margins. Scanning electron microscopy of young primordia and analyses of leaf
      developmental-marker gene expression in mutant apices reveal that RGD2 functions
      during recruitment of leaf founder cells and during expansive growth of leaf
      primordia. Overall, these phenotypes suggest that development is uncoordinated in
      Rgd2-R(-) mutant leaves, so that leaf components and tissues may develop quasi
      independently. Models whereby RGD2 is required for developmental signaling during
      the initiation, anatomical patterning, and lateral expansion of maize leaves are
      discussed.

PMID- 15950611
TI  - Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and
      identifies a subgroup of mesencephalic dopaminergic progenitor neurons during
      mouse development.
AB  - Recent studies of mouse mutant aphakia have implicated the homeobox gene Pitx3 in
      the survival of substantia nigra dopaminergic neurons, the degeneration of which
      causes Parkinson's disease. To directly investigate a role for Pitx3 in midbrain
      DA neuron development, we have analysed a line of Pitx3-null mice that also carry
      an eGFP reporter under the control of the endogenous Pitx3 promoter. We show that
      the lack of Pitx3 resulted in a loss of nascent substantia nigra dopaminergic
      neurons at the beginning of their final differentiation. Pitx3 deficiency also
      caused a loss of tyrosine hydroxylase (TH) expression specifically in the
      substantia nigra neurons. Therefore, our study provides the first direct evidence
      that the aphakia allele of Pitx3 is a hypomorph and that Pitx3 is required for
      the regulation of TH expression in midbrain dopaminergic neurons as well as the
      generation and/or maintenance of these cells. Furthermore, using the targeted GFP
      reporter as a midbrain dopaminergic lineage marker, we have identified previously
      unrecognised ontogenetically distinct subpopulations of dopaminergic cells within
      the ventral midbrain based on their temporal and topographical expression of
      Pitx3 and TH. Such an expression pattern may provide the molecular basis for the
      specific dependence of substantia nigra DA neurons on Pitx3.

PMID- 15950612
TI  - Testicular expression of small ubiquitin-related modifier-1 (SUMO-1) supports
      multiple roles in spermatogenesis: silencing of sex chromosomes in spermatocytes,
      spermatid microtubule nucleation, and nuclear reshaping.
AB  - SUMO-1 is a member of a ubiquitin-related family of proteins that mediates
      important post-translational effects affecting diverse physiological functions.
      Whereas SUMO-1 is detected in the testis, little is known about its reproductive
      role in males. Herein, cell-specific SUMO-1 was localized in freshly isolated,
      purified male germ cells and somatic cells of mouse and rat testes using Western
      analysis, high-resolution single-cell bioimaging, and in situ confocal microscopy
      of seminiferous tubules. During germ cell development, SUMO-1 was observed at low
      but detectable levels in the cytoplasm of spermatogonia and early spermatocytes.
      SUMO-1 appeared on gonosomal chromatin during zygotene when chromosome homologues
      pair and sex chromatin condensation is initiated. Striking SUMO-1 increases in
      the sex body of early-to-mid-pachytene spermatocytes correlated with timing of
      additional sex chromosome condensation. Before the completion of the first
      meiotic division, SUMO-1 disappeared from the sex body when X and Y chromosomal
      activity resumed. Together, these data indicate that sumoylation may be involved
      in non-homologous chromosomal synapsis, meiotic sex chromosome inactivation, and
      XY body formation. During spermiogenesis, SUMO-1 localized in chromocenters of
      certain round spermatids and perinuclear ring and centrosomes of elongating
      spermatids, data implicating SUMO-1 in the process of microtubule nucleation and
      nuclear reshaping. STAT-4, one potential target of sumoylation, was located along
      the spermatid nuclei, adjacent but not co-localized with SUMO-1. Androgen
      receptor-positive Leydig, Sertoli, and some peritubular myoepithelial cells
      express SUMO-1, findings suggesting a role in modulating steroid action.
      Testicular SUMO-1 expression supports its specific functions in inactivation of
      sex chromosomes during meiosis, spermatid microtubule nucleation, nuclear
      reshaping, and gene expression.

PMID- 15950613
TI  - Molecular evidence from Ciona intestinalis for the evolutionary origin of
      vertebrate sensory placodes.
AB  - Cranial sensory placodes are focused areas of the head ectoderm of vertebrates
      that contribute to the development of the cranial sense organs and their
      associated ganglia. Placodes have long been considered a key character of
      vertebrates, and their evolution is proposed to have been essential for the
      evolution of an active predatory lifestyle by early vertebrates. Despite their
      importance for understanding vertebrate origins, the evolutionary origin of
      placodes has remained obscure. Here, we use a panel of molecular markers from the
      Six, Eya, Pax, Dach, FoxI, COE and POUIV gene families to examine the tunicate
      Ciona intestinalis for evidence of structures homologous to vertebrate placodes.
      Our results identify two domains of Ciona ectoderm that are marked by the genetic
      cascade that regulates vertebrate placode formation. The first is just anterior
      to the brain, and we suggest this territory is equivalent to the
      olfactory/adenohypophyseal placodes of vertebrates. The second is a bilateral
      domain adjacent to the posterior brain and includes cells fated to form the
      atrium and atrial siphon of adult Ciona. We show this bares most similarity to
      placodes fated to form the vertebrate acoustico-lateralis system. We interpret
      these data as support for the hypothesis that sensory placodes did not arise de
      novo in vertebrates, but evolved from pre-existing specialised areas of ectoderm
      that contributed to sensory organs in the common ancestor of vertebrates and
      tunicates.

PMID- 15950614
TI  - A consensus Oct1 binding site is required for the activity of the Xenopus Cdx4
      promoter.
AB  - Cdx homeodomain transcription factors have multiple roles in early vertebrate
      development. Furthermore, mis-regulation of Cdx expression has been demonstrated
      in metaplasias and cancers of the gut epithelium. Given the importance of Cdx
      genes in development and disease, the mechanisms underlying their expression are
      of considerable interest. We report an analysis of the upstream regulatory
      regions from the amphibian Xenopus laevis Cdx4 gene. We show that a GFP reporter
      containing 2.8 kb upstream of the transcription start site is expressed in the
      posterior of transgenic embryos. Deletion analysis of the upstream sequence
      reveals that a 247-bp proximal promoter fragment will drive posterior expression
      in transgenic embryos. We show that 63 bp of upstream sequence, that includes a
      consensus site for POU-domain octamer-binding proteins, retains significant
      promoter activity. Co-expression of the octamer-binding protein Oct1 induces
      expression from a Cdx4 reporter and mutation of the octamer site abolishes
      activity of the same reporter. We show that the octamer site is highly conserved
      in the promoters of the human, mouse, chicken, and zebrafish Cdx4 genes and
      within the promoters of amphibian Cdx1 and Cdx2. These data suggest a conserved
      function for octamer-binding proteins in the regulation of Cdx family members.

PMID- 15950615
TI  - RNA interference during spermatogenesis in mice.
AB  - Spermatogenesis consists of complex cellular and developmental processes, such as
      the mitotic proliferation of spermatogonial stem cells, meiotic division of
      spermatocytes, and morphogenesis of haploid spermatids. In this study, we show
      that RNA interference (RNAi) functions throughout spermatogenesis in mice. We
      first carried out in vivo DNA electroporation of the testis during the first wave
      of spermatogenesis to enable foreign gene expression in spermatogenic cells at
      different stages of differentiation. Using prepubertal testes at different ages
      and differentiation stage-specific promoters, reporter gene expression was
      predominantly observed in spermatogonia, spermatocytes, and round spermatids.
      This method was next applied to introduce DNA vectors that express small hairpin
      RNAs, and the sequence-specific reduction in the reporter gene products was
      confirmed at each stage of spermatogenesis. RNAi against endogenous Dmc1, which
      encodes a DNA recombinase that is expressed and functionally required in
      spermatocytes, led to the same phenotypes observed in null mutant mice. Thus,
      RNAi is effective in male germ cells during mitosis and meiosis as well as in
      haploid cells. This experimental system provides a novel tool for the rapid,
      first-pass assessment of the physiological functions of spermatogenic genes in
      vivo.

PMID- 15950616
TI  - Ci-Tbx6b and Ci-Tbx6c are key mediators of the maternal effect gene Ci-macho1 in
      muscle cell differentiation in Ciona intestinalis embryos.
AB  - Maternally deposited mRNA encoding the Zic family zinc-finger protein Ci-macho1
      is a determinant responsible for muscle cell differentiation in Ciona
      intestinalis embryos. In a previous study, we identified possible Ci-macho1
      downstream genes, which include seven transcription factor genes and seven
      signaling molecule genes (Yagi, K., Satoh, N., Satou, Y., 2004. Identification of
      downstream genes of the ascidian muscle determinant gene Ci-macho1. Dev. Biol.
      274, 478-489), suggesting complex Ci-macho1 downstream cascades. Here, we show
      that of the Ci-macho1 downstream genes, only Ci-Tbx6b and Ci-Tbx6c promote
      ectopic differentiation of muscle cells when misexpressed in non-muscle
      blastomeres. Overexpression of Ci-Tbx6b or Ci-Tbx6c in Ci-macho1 knockdown
      embryos is able to compensate for the functional loss of Ci-macho1 and promote
      differentiation of muscle cells. In addition, we show that knockdown of each of
      Ci-Tbx6b or Ci-Tbx6c suppresses the initiation of muscle protein gene expression,
      and both gene products appear to recognize a similar binding sequence. However,
      later expression of muscle protein genes at the tailbud stage is only reduced in
      Ci-Tbx6b knockdown embryos and undisturbed in Ci-Tbx6c knockdown embryos.
      Although ectopic expression or knockdown of Ci-ZicL alone does not affect muscle
      cell differentiation, simultaneous knockdown of Ci-Tbx6b, Ci-Tbx6c, and Ci-ZicL
      completely abolishes muscle cell differentiation, as in the case of knockdown of
      Ci-macho1 and Ci-ZicL. These results strongly suggest that muscle cell
      differentiation in Ciona embryos is controlled by four key factors: maternal
      macho1 and zygotic Tbx6b, Tbx6c, and ZicL. The two T-box genes are primary
      mediators of macho1 function, and cooperation between the zygotically expressed
      transcription factors is indispensable for muscle cell differentiation in Ciona
      embryos.

PMID- 15950617
TI  - Nuclear envelope remodeling during mouse spermiogenesis: postmeiotic expression
      and redistribution of germline lamin B3.
AB  - Lamins are members of a multigene family of structural nuclear envelope (NE)
      proteins. Differentiated mammalian somatic cells express lamins A, C, B1, and B2.
      The composition and organization of the nuclear lamina of mammalian spermatogenic
      cells differ significantly from that of somatic cells as they express lamin B1 as
      well as two short germ line-specific isoforms, namely lamins B3 and C2. Here we
      describe in detail the expression pattern and localization of lamin B3 during
      mouse spermatogenesis. By combining RT-PCR, immunoblotting, and
      immunofluorescence microscopy, we show that lamin B3 is selectively expressed
      during spermiogenesis (i.e., postmeiotic stages of spermatogenesis). In round
      spermatids, lamin B3 is distributed in the nuclear periphery and, notably, also
      in the nucleoplasm. In the course of spermiogenesis, lamin B3 becomes
      redistributed as it concentrates progressively to the posterior pole of spermatid
      nuclei. Our results show that during mammalian spermiogenesis the nuclear lamina
      is composed of B-type isoforms only, namely the ubiquitous lamin B1 and the
      germline-specific lamin B3. Lamin B3 is the first example of a mammalian lamin
      that is selectively expressed during postmeiotic stages of spermatogenesis.

PMID- 15950618
TI  - Generation of biologically active endostatin fragments from human collagen XVIII
      by distinct matrix metalloproteases.
AB  - Endostatin, a potent inhibitor of endothelial cell proliferation, migration,
      angiogenesis and tumor growth, is proteolytically cleaved from the C-terminal
      noncollagenous NC1 domain of type XVIII collagen. We investigated the endostatin
      formation from human collagen XVIII by several MMPs in vitro. The generation of
      endostatin fragments differing in molecular size (24-30 kDa) and in N-terminal
      sequences was identified in the cases of MMP-3, -7, -9, -13 and -20. The cleavage
      sites were located in the protease-sensitive hinge region between the
      trimerization and endostatin domains of NC1. MMP-1, -2, -8 and -12 did not show
      any significant activity against the C-terminus of collagen XVIII. The anti
      proliferative effect of the 20-kDa endostatin, three longer endostatin-containing
      fragments generated in vitro by distinct MMPs and the entire NC1 domain, on bFGF
      stimulated human umbilical vein endothelial cells was established. The anti
      migratory potential of some of these fragments was also studied. In addition,
      production of endostatin fragments between 24-30 kDa by human hepatoblastoma
      cells was shown to be due to MMP action on type XVIII collagen. Our results
      indicate that certain, especially cancer-related, MMP family members can generate
      biologically active endostatin-containing polypeptides from collagen XVIII and
      thus, by releasing endostatin fragments, may participate in the inhibition of
      endothelial cell proliferation, migration and angiogenesis.

PMID- 15950619
TI  - Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/CCN2.
AB  - Transforming growth factor-beta (TGFbeta) drives fibrosis in diseases such as
      diabetic nephropathy (DN). Connective tissue growth factor (CTGF; CCN2) has also
      been implicated in this, but the molecular mechanism is unknown. We show that
      CTGF enhances the TGFbeta/Smad signaling pathway by transcriptional suppression
      of Smad 7 following rapid and sustained induction of the transcription factor
      TIEG-1. Smad 7 is a known antagonist of TGFbeta signaling and TIEG-1 is a known
      repressor of Smad 7 transcription. CTGF enhanced TGFbeta-induced phosphorylation
      and nuclear translocation of Smad 2 and Smad 3 in mesangial cells. Antisense
      oligonucleotides directed against TIEG-1 prevented CTGF-induced downregulation of
      Smad 7. CTGF enhanced TGFbeta-stimulated transcription of the SBE4-Luc reporter
      gene and this was markedly reduced by TIEG-1 antisense oligonucleotides.
      Expression of the TGFbeta-responsive genes PAI-1 and Col III over 48 h was
      maximally stimulated by TGFbeta+CTGF compared to TGFbeta alone, while CTGF alone
      had no significant effect. TGFbeta-stimulated expression of these genes was
      markedly reduced by both CTGF and TIEG-1 antisense oligonucleotides, consistent
      with the endogenous induction of CTGF by TGFbeta. We propose that under
      pathological conditions, where CTGF expression is elevated, CTGF blocks the
      negative feedback loop provided by Smad 7, allowing continued activation of the
      TGFbeta signaling pathway.

PMID- 15950620
TI  - Microparticles released by human neutrophils adhere to erythrocytes in the
      presence of complement.
AB  - The release of cell surface-derived microparticles, or ectosomes, has now been
      described for many different cell types. In various diseases characterized by
      systemic inflammation, the numbers of ectosomes released from specific cell-types
      are found increased manifold in the circulation. Their pro-inflammatory and pro
      coagulant functions make them potentially important actors in disease
      establishment and/or progression. Until now, ectosomes have been believed to be
      free in the circulation. Herein, we provide evidence for sequestration of
      ectosomes derived from human polymorphonuclear neutrophils to erythrocytes,
      similarly to immune complexes. We show that ectosomes activate and bind
      complement in vitro. In whole blood, opsonization of ectosomes by complement
      mediated their immune adherence to erythrocytes through complement receptor 1.
      Taken together, our data suggest an important role for complement and
      erythrocytes in the sequestration, and possibly clearance, of blood-borne
      ectosomes stemming from neutrophils. The immune adherence described here may
      modify the biological activity and function of ectosomes.

PMID- 15950621
TI  - Induction of lamellipodia by Kalirin does not require its guanine nucleotide
      exchange factor activity.
AB  - Guanine nucleotide exchange factor (GEF) domains of the Dbl family occur in a
      variety of proteins that include multiple protein-protein and protein-lipid
      interaction domains. We used an epithelial-derived cell line to investigate the
      mechanisms by which the two GEF domains of Kalirin, a neuronal Rho GEF, influence
      morphology. As expected, Kal-GEF1, an efficient GEF for Rac1 and RhoG, induced
      the formation of lamellipodia resembling those induced by active Rac1. Although
      Kal-GEF1 activated Rac and Pak, its ability to induce formation of lamellipodia
      was not blocked by dominant negative Rho GTPases or by catalytically inactive
      Pak. Consistent with this, a catalytically inactive mutant of Kal-GEF1 induced
      formation of lamellipodia and activated Pak. Active Pak was required for the GEF
      activity independent effect of Kal-GEF1 and the lamellipodia produced were filled
      with ribs of filamentous actin. Kal-GEF1 and a GEF-dead mutant co
      immunoprecipitated with Pak. The interaction of Kal-GEF1 with Pak is indirect and
      requires the regulatory protein binding domain of Pak. Filamin A, which is known
      to interact with and activate Pak, binds to both catalytically active and
      inactive Kal-GEF1, providing a link by which catalytically inactive Kal-GEF1 can
      activate Pak and induce lamellipodia. Together, our results indicate that Kal
      GEF1 induces lamellipodia through activation of Pak, where GEF activity is not
      required. GEF-activity-independent effects on downstream targets may be a general
      property of RhoGEFs.

PMID- 15950622
TI  - Analysis methods of human cell migration.
AB  - The autonomous migration of specialized cells is an essential characteristic in
      both physiological and pathological functions in the adult human organism.
      Leukocytes, fibroblasts, and stem cells, but also tumor cells, are thus the
      subject of intense investigation in a broad range of research fields. A wide
      spectrum of methods have therefore been established to analyze chemokinetic and
      chemotactic cell migration, ranging from easy-to-handle two-dimensional surface
      migration assays to highly specialized three-dimensional and intravital analysis
      methods. It is now manifest that the results obtained with these various
      migration assays substantially differ. This review therefore gives an overview of
      the migration assays which are currently in use, describes the methods, and
      critically enlightens the particular advantages and disadvantages of each method.

PMID- 15950623
TI  - Control of density-dependent, cell state-specific signal transduction by the cell
      adhesion molecule CEACAM1, and its influence on cell cycle regulation.
AB  - Growth factor receptors, extracellular matrix receptors, and cell-cell adhesion
      molecules co-operate in regulating the activities of intracellular signaling
      pathways. Here, we demonstrate that the cell adhesion molecule CEACAM1 co
      regulates growth-factor-induced DNA synthesis in NBT-II epithelial cells in a
      cell-density-dependent manner. CEACAM1 exerted its effects by regulating the
      activity of the Erk 1/2 MAP kinase pathway and the expression levels of the
      cyclin-dependent kinase inhibitor p27(Kip1). Interestingly, both inhibitory and
      stimulatory effects were observed. Confluent cells continuously exposed to fetal
      calf serum showed little Erk activity and DNA synthesis compared with sparse
      cells. Under these conditions, anti-CEACAM1 antibodies strongly stimulated Erk
      activation, decreased p27 expression, and induced DNA synthesis. In serum-starved
      confluent cells, re-addition of 10% fetal calf serum activated the Erk pathway,
      decreased p27 expression, and stimulated DNA synthesis to the same levels as in
      sparse cells. Under these conditions anti-CEACAM1 antibodies de-activated Erk,
      restored the level of p27, and inhibited DNA synthesis. These data indicate that
      CEACAM1 mediates contact inhibition of proliferation in cells that are constantly
      exposed to growth factors, but co-activates growth-factor-induced proliferation
      in cells that have been starved for growth factors; exposure to extracellular
      CEACAM1 ligands reverts these responses.

PMID- 15950624
TI  - Deubiquitination by proteasome is coordinated with substrate translocation for
      proteolysis in vivo.
AB  - The 26S proteasome mediates degradation of protein substrates labeled with polyUb
      chains. After recognition by the 19S proteasome regulatory complex, polyUb chains
      are disassembled and substrates are processed in the 20S core of proteasome.
      However, the exact relationship of degradation-associated deubiquitination to
      substrate processing remains unclear. Here, using Ub-based tagging strategies, we
      provided evidence that removable polyUb chains serve as the signal for
      proteolytic processing of ubiquitinated substrates. We showed that inhibition of
      the proteasome by proteasome inhibitor MG132 results in trapping of the substrate
      in the proteasome. Such a trapping allows proteasomal cleavage of attached non
      removable Ub mutant (UbV75,76), which is otherwise a "difficult" deubiquitination
      substrate. Characterization of deubiquitination and degradation intermediates,
      generated due to incomplete proteolytic inhibition, revealed changes in
      proteolytic cleavage sites, within the Gal4-VP16 model substrate, suggesting that
      the copy number of attached UbV75,76 affects substrate processing. Conversion of
      lysine48 to arginine48 in UbV75,76 did not have significant effect on in vivo
      polyubiquitination of multiple Ub-fused substrates, but considerably reduced
      proteolytic intermediates. Taken together, the results support a model in which
      deubiquitination process is a crucial event for proteolysis of ubiquitinated
      substrates and such an event is coordinated with substrate translocation.

PMID- 15950625
TI  - Hysterosalpingography.
AB  - OBJECTIVE: To demonstrate the value of the hysterosalpingogram in the evaluation
      of infertility. CONCLUSION(S): Hysterosalpingography, which should be done in the
      follicular phase of the cycle, evaluates the contour of the uterine cavity,
      cervical canal, and tubal lumina. Other than being diagnostic, it can prove to be
      therapeutic. The instrument used to introduce the radio-opaque medium should be
      chosen to give the least discomfort and to cause no leakage of dye from the
      cervix. Water-soluble medium is usually used rather than an oil-based medium.
      Fluoroscopy with image intensification gives the best results. Insufficient dye
      injection will give an incomplete study. Too much dye injection, especially under
      pressure, might cause extravasation of the dye into the vascular system or
      conceal the fimbrial ends of the tubes.

PMID- 15950626
TI  - Why is the clinical acceptance of gonadotropin-releasing hormone antagonist
      cotreatment during ovarian hyperstimulation for in vitro fertilization so slow?
AB  - The use of GnRH antagonist rather than agonist cotreatment during ovarian
      hyperstimulation for IVF is not widely accepted. Possible benefits, current
      shortcomings, and avenues for future development are discussed.

PMID- 15950627
TI  - Opinions about new reproductive genetic technologies: hopes and fears for our
      genetic future.
AB  - OBJECTIVE: To identify underlying beliefs and values shaping Americans' opinions
      about the appropriate use of new reproductive genetic technologies (RGTs),
      including preimplantation genetic diagnosis, hypothetical genetic modification,
      and sperm sorting for sex selection. DESIGN: Scenarios with ethical dilemmas
      presented to 21 focus groups organized by sex, race/ethnicity, religion, age,
      education, and parental status. SETTING: A city in each state: California,
      Colorado, Massachusetts, Michigan, and Tennessee. PARTICIPANT(S): One hundred and
      eighty-one paid volunteers, ages 18 to 68. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Beliefs and values that shape participants' opinions about the
      appropriate use of new RGTs. RESULT(S): Regardless of demographic
      characteristics, focus group participants considered six key factors when
      determining the appropriateness of using RGTs: [1] whether embryos would be
      destroyed; [2] the nature of the disease or trait being avoided or sought; [3]
      technological control over "natural" reproduction; [4] the value of suffering,
      disability, and difference; [5] the importance of having genetically related
      children; and [6] the kind of future people desire or fear. CONCLUSION(S): Public
      opinions about the appropriate use of RGTs are shaped by numerous complementary
      and conflicting values beyond classic abortion arguments. Clinicians and policy
      makers have the opportunity to consider these opinions when creating messages and
      crafting policy.

PMID- 15950628
TI  - Fertility preservation and reproduction in cancer patients.
AB  - Cancer treatment often results in reduced fertility. Cancer patients should be
      informed of options for fertility preservation and future reproduction prior to
      cancer treatment. Reproduction in the context of cancer raises a number of
      ethical issues related to both patient and offspring welfare.

PMID- 15950629
TI  - Obesity does not impact implantation rates or pregnancy outcome in women
      attempting conception through oocyte donation.
AB  - OBJECTIVE: To independently evaluate the effect of body mass index (BMI) on
      implantation, pregnancy, and incidence of spontaneous miscarriage using the donor
      oocyte recipient model. DESIGN: Institutional Review Board-approved retrospective
      data analyses of donor oocyte cycles from 1999 to 2004. SETTING: Private assisted
      reproductive technology (ART) center. PATIENT(S): Five hundred thirty-six first
      cycle recipients of donor oocytes. INTERVENTION(S): Data were collected from the
      first cycle of each donor oocyte recipient included in the study. The body mass
      index (BMI) of each recipient was calculated using the formula weight (in
      kilograms)/height (in meters squared). Patients were divided into four groups
      based on BMI: underweight, normal, overweight, and obese. Pregnancy outcomes in
      each group were compared. MAIN OUTCOME MEASURE(S): Body mass index, implantation
      rate, pregnancy rate (PR), miscarriage rate. RESULT(S): There were no
      statistically significant differences in the implantation rates, ongoing PRs, or
      spontaneous abortion rates among patients in the four BMI groups. When further
      divided into those patients receiving blastocyst vs. day 3 transfers, there was
      still no effect of BMI on implantation rate, PR, or loss rate among the
      blastocyst or day 3 donor oocyte recipients. CONCLUSION(S): Body mass index has
      no adverse impact on implantation or reproductive outcome in donor oocyte
      recipients. Therefore, obesity does not appear to exert a negative effect on
      endometrial receptivity.

PMID- 15950630
TI  - Occurrence and developmental consequences of vacuoles throughout preimplantation
      development.
AB  - OBJECTIVE: Since little is known about the actual incidence and fate of vacuoles
      at different stages of development this preliminary study was set up to
      accurately measure vacuoles and track them to day 5. DESIGN: Prospective study.
      SETTING: Women's General Hospital in Austria. PATIENT(S): A total of 223
      consecutive IVF and intracytoplasmic sperm injection (ICSI) cycles (206
      patients). INTERVENTION(S): Accurate measurement of vacuoles. Affected gametes
      and embryos were cultured individually and tracked until day 5. MAIN OUTCOME
      MEASURE(S): Size and number of vacuoles, fertilization rate, blastocyst formation
      rate, blastocyst quality. RESULT(S): There was a significant relationship between
      size of the vacuole (cut-off value 14 microm) and fertilization (P<.05). At
      zygote stage the incidence of vacuoles was higher (P<.01) in ICSI (11.6%) than in
      IVF (5.3%). Only 32.2% of affected ICSI-embryos reached blastocyst stage on day 5
      compared with 53.0% of the normal ones (P<.001). In terms of blastocyst formation
      vacuolization on day 4 (P<.001) turned out to be the most severe one. At
      blastocyst stage inner cell mass was affected less frequently than the
      trophectoderm (P<.05). CONCLUSION(S): Three types of vacuoles could be
      identified: (1) those already present at oocyte collection, which develop during
      maturation (day 0); (2) those artificially created by ICSI (day 1); and (3) those
      accompanied with developmental arrest (day 4). The later that vacuoles arose, the
      more detrimental their effect on blastocyst formation.

PMID- 15950631
TI  - Efficacy and tolerability of vaginal progesterone capsules (Utrogest 200)
      compared with progesterone gel (Crinone 8%) for luteal phase support during
      assisted reproduction.
AB  - OBJECTIVE: To demonstrate the comparative efficacy and tolerability of capsules
      containing 200 mg of P (Utrogest 200) or Crinone 8% gel for luteal phase and
      early pregnancy support during assisted reproduction techniques (ART). DESIGN:
      Prospective, multicenter, randomized, controlled, open, parallel-group Phase III
      trial. SETTING: Seventeen German IVF centers. PATIENT(S): Four hundred thirty
      women who underwent their first IVF or intracytoplasmic sperm injection cycle
      were randomized after successful transfer of two or three embryos from July 1999
      through September 2001. INTERVENTION(S): Patients vaginally applied capsules
      containing 200 mg of P (Utrogest 200) three times per day or containing Crinone
      8% gel twice per day. Therapy was started in the evening of the ET day and
      continued up to 10 weeks in pregnant women. If the pregnancy test proved to be
      negative, application was stopped. MAIN OUTCOME MEASURE(S): Ongoing pregnancy
      rate at the end of the study (12th week of gestation). Secondary outcomes were
      rate of implantation and abortion, number and reasons of withdrawals, as well as
      adverse events, assessment of tolerability, and acceptance. RESULT(S): There were
      no relevant differences in demographic and other characteristics between the two
      groups. Ongoing pregnancy rates were 25.2% in the Utrogest 200 group and 22.2% in
      the Crinone 8% group when patients were analyzed who normally completed the
      trial. In the Utrogest 200 vs. the Crinone 8% group, the implantation rate (14.7%
      vs. 11.9%) and abortion rate (18.2% vs. 19.1%) were not statistically different.
      The rate of withdrawals at the individual visits also did not differ between
      treatment groups. Tolerability of both drugs was good, and very few study drug
      related adverse events were observed in both groups. CONCLUSION(S): The luteal
      phase support in ART cycles with Utrogest 200 capsules (three times per day) or
      Crinone 8% gel (two times per day) by the vaginal route resulted in similar
      outcomes with respect to implantation, ongoing pregnancy, and abortion rates. The
      two recommended regimens of P supplementation in ART proved to be equivalent and
      safe.

PMID- 15950632
TI  - Preterm birth and low birth weight after assisted reproductive technology-related
      pregnancy in Australia between 1996 and 2000.
AB  - OBJECTIVE: To describe patterns of preterm birth and low birth weight (LBW) for
      infants born after assisted reproductive technology (ART) and determine whether
      these were associated with maternal or treatment characteristics. DESIGN:
      Retrospective cohort study of national population data of infants conceived
      through ART. SETTING: Australian birth records from 1996 to 2000. PATIENT(S):
      Eighteen thousand, four hundred twenty-nine liveborn and stillborn infants
      conceived through ART. INTERVENTION(S): In vitro fertilization, intracytoplasmic
      sperm injection, and gamete intrafallopian transfer. MAIN OUTCOME MEASURE(S):
      Preterm birth and LBW. RESULT(S): Preterm birth and LBW were more common among
      singletons and twins conceived with IVF and born to nulliparous mothers. Preterm
      birth and LBW were, respectively, 1.3 times and 1.5 times more likely to occur
      among singletons conceived by transfer of fresh embryos, compared with transfer
      of frozen embryos. Preterm birth and LBW was more common among couples who had
      female-factor infertility compared with male-factor infertility. CONCLUSION(S):
      The transfer of fresh embryos and female-factor infertility were independently
      associated with preterm birth and LBW for both singletons and twins after ART.

PMID- 15950633
TI  - T-helper 2 and 3 type immunity to trophoblast in successful in vitro
      fertilization-embryo transfer.
AB  - OBJECTIVE: To determine whether peripheral blood mononuclear cell (PBMC)
      secretion of T-helper (Th)-1 type cytokines and Th-2 and Th-3 type cytokines in
      women undergoing in vitro fertilization-embryo transfer (IVF-ET) is associated
      with therapeutic failure and success, respectively. DESIGN: Cohort study.
      SETTING: Academic medical center. PATIENT(S): One hundred one women undergoing
      IVF-ET and 19 fertile controls. INTERVENTION(S): Peripheral blood was obtained
      from women undergoing IVF-ET before oocyte retrieval and from 19 nonpregnant
      fertile controls. The PBMCs were cultured in the presence or absence of a protein
      extract from either a trophoblast cell line or sperm membrane. MAIN OUTCOME
      MEASURE(S): Supernatants from PBMC cultures were tested by enzyme-linked
      immunoabsorbent assay (ELISA) for the Th-1 type cytokines tumor necrosis factor
      alpha (TNF)-alpha) and interferon-gamma (IFN)-gamma), the Th-2 type cytokines
      interleukin (IL)-6 and IL-10, and the Th-3 type cytokine transforming growth
      factor (TGF)-beta1. RESULT(S): Levels of IL-6 and IL-10 were significantly higher
      in controls than in infertile women with endometriosis, and levels of IL-10 were
      higher in controls than in women with unexplained infertility. No differences
      were found in unstimulated levels of TNF-alpha, IFN-gamma, or TGF-beta1 between
      infertile patients and controls. In trophoblast-stimulated PBMC cultures, levels
      of TGF-beta1 were significantly lower in subjects who experienced failed compared
      with ongoing pregnancies. CONCLUSION(S): Baseline PBMC secretion of IL-6 and IL
      10 is higher in fertile controls than in women with endometriosis, and IL-10
      secretion is also higher than in women with unexplained infertility. Trophoblast
      stimulated PBMC secretion of TGF-beta1 is positively associated with the
      establishment of successful pregnancy in women undergoing IVF-ET. Our study
      provides novel evidence to support a faciliatory role of Th-2 and Th-3 type
      responses to trophoblast in early pregnancy.

PMID- 15950634
TI  - Infliximab may reverse the toxic effects induced by tumor necrosis factor alpha
      in human spermatozoa: an in vitro model.
AB  - OBJECTIVE: To examine the toxic effects of tumor necrosis factor alpha (TNF
      alpha) on ejaculated spermatozoa and evaluate the ability of infliximab to
      reverse these effects. DESIGN: Prospective controlled study. SETTING: Cleveland
      Clinic Foundation, Cleveland, Ohio. PATIENT(S): Thirty-one healthy sperm donors.
      INTERVENTION(S): Exposure of human spermatozoa to varying concentrations of TNF
      alpha (100, 300, 400, 500 pg/mL, and 2.5 microg/mL) and infliximab (400
      microg/mL). MAIN OUTCOME MEASURE(S): Sperm motility, functional integrity of
      plasma membrane, and DNA fragmentation. RESULT(S): Spermatozoa quality declined
      following incubation with TNF-alpha in a dose-dependent and time-dependent
      manner. Sperm motility and membrane integrity were higher in the samples
      incubated with TNF-alpha plus infliximab than in the samples treated with TNF
      alpha only. These parameters improved significantly and were comparable with both
      controls and sperm incubated with infliximab alone. Similarly, the percentage of
      spermatozoa with DNA fragmentation improved significantly following incubation
      with TNF-alpha plus infliximab and again was comparable with both controls and
      sperm incubated with infliximab alone. CONCLUSION(S): Spermatozoa may be exposed
      to abnormal levels of TNF-alpha in the male reproductive tract or during their
      passage into the female reproductive tract (in cases of endometriosis). Exposing
      spermatozoa to pathological concentrations of TNF-alpha can result in significant
      loss of their functional and genomic integrity. Infliximab could potentially be
      used to help treat female infertility caused by endometriosis in those with
      elevated levels of TNF-alpha in their peritoneal fluid.

PMID- 15950635
TI  - Reproductive prognosis in male patients with azoospermia at the time of cancer
      diagnosis.
AB  - OBJECTIVE: Fertility status evaluation in patients found azoospermic at the time
      of malignancy diagnosis. DESIGN: Case series follow-up. SETTING: University
      Hospital Sperm Banking service. PATIENT(S): Male cancer patients found
      azoospermic between 1986 and June 2000. INTERVENTION(S): Patients were
      interviewed about their reproductive history and were invited for a free semen
      analysis. MAIN OUTCOME MEASURE(S): Pregnancy rate (PR) and percentage of patients
      with viable spermatozoa in the ejaculate. RESULT(S): Sixty-five patients were
      enrolled; 16 were lost at follow-up, 7 died, and 42 were followed to the end of
      the study. The median (range) time of follow-up for the 42 remaining patients was
      9 years (2-14 years). Seventeen patients had wanted to father a child; 12 had a
      child (71%, 95% confidence interval [CI] 48%-88%). Semen analysis results were
      available in 11 patients. Resumption of spermatogenesis was documented in 9 cases
      (82%, 95% CI 53%-97%). CONCLUSION(S): Spontaneous fertility recovery is frequent
      in patients who are azoospermic at the time of cancer diagnosis.

PMID- 15950636
TI  - Relationship between the duration of sexual abstinence and semen quality:
      analysis of 9,489 semen samples.
AB  - OBJECTIVE: To evaluate the relationship between duration of sexual abstinence and
      various characteristics of normal and subnormal semen. DESIGN: A retrospective
      study based on computerized data. SETTING: Fertility and IVF unit at a university
      medical center. PATIENT(S): Nine thousand, four hundred eighty-nine semen samples
      from 6,008 patients were analyzed according to the World Health Organization
      (WHO) manual and grouped according to sperm concentration (10(6)/mL) into severe
      (0.2-4 x 10(6)), moderate (>4-10 x 10(6)), and mild (>10-19.99 x 10(6))
      oligozoospermia, and normozoospermia (> or =20-250 x 10(6)) groups. MAIN OUTCOME
      MEASURE(S): In each group mean values of semen volume, sperm concentration,
      percentage of motile sperm and of normal morphology (according to WHO or Kruger
      criteria), total sperm count, and total motile sperm count per ejaculate were
      related to duration of abstinence. RESULT(S): Among the 3,506 oligozoospermic
      samples, the peak mean sperm motility of 30.3% was observed after 1 day of
      abstinence. Similarly, the mean percentage of normal morphology among mild
      moderate oligozoospermic samples (n = 2,260) reached peak values of 7.4%-8.6%
      between 0-2 days of abstinence. The 5,983 normozoospermic samples showed a
      significant decrease in the percentage of sperm motility and normal morphology to
      mean values of 33.1% and 7.0%, respectively, on days 11-14 of sexual abstinence.
      CONCLUSION(S): Our data challenge the role of abstinence in male infertility
      treatments and suggest that to present the best possible semen samples, patients
      with male factor infertility should collect the semen after just 1 day of sexual
      abstinence. Patients presenting normal sperm analysis or sperm donors for
      cryopreservation purposes should be advised not to exceed 10 days of sexual
      abstinence.

PMID- 15950637
TI  - Toward using stable spermatozoal RNAs for prognostic assessment of male factor
      fertility.
AB  - OBJECTIVE: To establish the stability of spermatozoal RNAs as a means to validate
      their use as a male fertility marker. DESIGN: Semen samples were randomly
      selected for 1 of 3 cryopreservation treatments. SETTING: An academic research
      environment. PATIENT(S): Men aged 19 to 55 years who had fathered a child by
      natural conception within the past 6 months. INTERVENTION(S): Ejaculates were
      collected by masturbation and total spermatozoan RNA was isolated from two semen
      samples of ideal quality; one sample of medium quality, having been subjected to
      an additional freeze-thaw cycle, and two samples of poor quality, having been
      subjected to a third freeze-thaw cycle. MAIN OUTCOME MEASURE(S): Labeled cDNAs
      were generated and then used to interrogate Atlas Nylon Human Toxicology 1.2
      microarrays. The spermatozoan transcriptomes were compared using a binomial
      approach. RESULT(S): The analysis identified a total of 228 unique spermatozoal
      transcripts among all samples. The medium quality sample shared 98% and 39% of
      its RNAs with the ideal and poor quality samples, respectively. A set of 36 RNAs
      resistant to insult were observed, some of which have been implicated in
      regulating male fertility, when all individuals were compared. CONCLUSION(S):
      These results support the view that a population of spermatozoal RNAs is rapidly
      degraded in response to insult, whereas another population appears protected from
      such damage. Because spermatozoal RNAs echo the gene expression of
      spermatogenesis, the latter is likely to prove useful as a clinical maker of
      fertility status.

PMID- 15950638
TI  - Absence of follicle-stimulating hormone receptor activating mutations in women
      with iatrogenic ovarian hyperstimulation syndrome.
AB  - OBJECTIVE: To analyze the FSH receptor gene in women with iatrogenic ovarian
      hyperstimulation syndrome (OHSS). DESIGN: Clinical and molecular studies.
      SETTING: University hospital and private clinic. PATIENT(S): Twenty-nine women
      who developed moderate or severe OHSS after ovulation induction for IVF. In
      addition, 50 fertile normal women were used as controls. INTERVENTION(S):
      Peripheral blood was used for DNA extraction. The exons 4, 7, 9, and 10 of the
      FSH receptor gene were amplified by polymerase chain reaction (PCR) followed by
      automatic direct sequencing. MAIN OUTCOME MEASURE(S): Hormonal results and
      automatic sequencing analysis. RESULT(S): Thirteen patients developed moderate
      OHSS and 16 patients developed the severe form of the syndrome. Automatic
      sequencing revealed no activating mutations in all patients studied. We found two
      known polymorphisms in linkage disequilibrium, Ala307Thr and Ser680Asn, in 79.3%
      of the patients (44.8% in heterozygous and 34.5% in homozygous state). These
      polymorphisms were found with similar frequency in the 50 normal fertile women.
      CONCLUSION(S): We conclude that the FSH receptor genotype did not play a
      significant role in the risk of iatrogenic OHSS in this cohort.

PMID- 15950639
TI  - Ovarian response and follicular development for single-dose and multiple-dose
      protocols for gonadotropin-releasing hormone antagonist administration.
AB  - OBJECTIVE: To determine the efficiency of a single-dose and a multiple-dose
      protocol for GnRH antagonist administration. DESIGN: Randomized clinical trial.
      SETTING: University hospital, tertiary medical center. PATIENT(S): Sixty-one
      patients undergoing controlled ovarian stimulation (COS) and IVF/ICSI.
      INTERVENTION(S): COS with either a multiple-dose (MD) or a single-dose (SD)
      protocol for GnRH antagonist (cetrorelix) administration, or with a long protocol
      (LP) for GnRH agonist (buserelin) administration, followed by oocyte retrieval,
      IVF/ICSI, and embryo transfer. MAIN OUTCOME MEASURE(S): Follicular development
      and serum levels of E2 and LH. RESULT(S): The SD protocol for cetrorelix was
      associated with a more reduced level of follicular development, lower levels of
      serum estradiol on the day of HCG administration, and a more reduced number of
      zygotes than the LP for buserelin. The pregnancy and implantation rates did not
      differ significantly for the three study groups. CONCLUSION(S): The MD and SD
      GnRH antagonist protocols were effective for preventing LH surge and appear to
      elicit an equivalent pregnancy rate to that corresponding to a LP GnRH agonist.
      In terms of follicular development, the SD protocol requires further
      modification, including flexible scheduling or possibly a small reduction of the
      dosage of the administered cetrorelix.

PMID- 15950640
TI  - Plasma adiponectin and insulin resistance in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine plasma adiponectin concentration in women with and
      without polycystic ovary syndrome (PCOS) and to assess possible correlations of
      adiponectin to the hormonal and metabolic parameters, including measures of
      insulin resistance (IR). DESIGN: Case-control study. SETTING: Tertiary-referral
      university hospital. PATIENT(S): One hundred eighty selected women were
      classified as follows: 45 obese (body mass index [BMI] >30 kg/m2) with PCOS; 45
      lean (BMI <25 kg/m2) with PCOS; 45 obese (BMI >30 kg/m2) without PCOS, and 45
      lean (BMI <25 kg/m2) without PCOS. INTERVENTION(S): Blood samples were collected
      from all women with or without PCOS between 8 and 11 am, after an overnight fast.
      MAIN OUTCOME MEASURE(S): Serum levels of luteinizing hormone (LH), follicle
      stimulating hormone (FSH), thyroid-stimulating hormone (TSH), free T4,
      testosterone (T), 17-alpha-hydroxyprogesterone, Delta4-androstenedione (Delta4
      A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), sex
      hormone-binding globulin (SHBG), insulin, and plasma levels of adiponectin and
      glucose. Measures of IR included fasting serum insulin, glucose-to-insulin ratio,
      and homeostasis model assessment (HOMA). RESULT(S): Adiponectin concentrations
      were found to be significantly decreased in women with PCOS and in obese women
      without PCOS as compared with lean women without PCOS. Adiponectin concentrations
      correlated inversely with body weight, BMI, fasting plasma glucose, serum
      insulin, Delta4-A, DHEA, DHEAS, and HOMA but correlated positively with serum T,
      SHBG, FAI, and glucose-to-insulin ratio. Multiple regression analysis showed that
      BMI, HOMA, Delta4-A, and insulin were independent determinants of adiponectin
      concentrations. CONCLUSION(S): Hypoadiponectinemia is evident in obese and lean
      women with PCOS with variable degree of IR; and it is suggested that IR per se or
      other metabolic abnormalities of PCOS are involved in the regulation of
      adiponectin concentration in women with PCOS.

PMID- 15950641
TI  - Phenotypic spectrum of polycystic ovary syndrome: clinical and biochemical
      characterization of the three major clinical subgroups.
AB  - OBJECTIVE: We tested the hypothesis that the three clinical phenotypes of
      polycystic ovary syndrome (PCOS) represent forms of the same metabolic disorder.
      DESIGN: Prospective cohort analysis. SETTING: University-based tertiary care.
      PATIENT(S): Three-hundred sixteen untreated consecutive women diagnosed as having
      PCOS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Each subject underwent an
      evaluation of ovulatory function, body habitus, acne, and hirsutism; serum free
      and total testosterone (T), 17-hydroxyprogesterone (17-HP), and DHEAS; and
      fasting plasma glucose and insulin levels. Insulin resistance and beta-cell
      function were assessed using the homeostatic assessment model equation (HOMA-IR
      and HOMA-beta-cell, respectively). RESULT(S): The Oligo+HA+Hirsutism phenotype
      was present in 48% of subjects, Oligo+HA in 29%, and Oligo+Hirsutism in 23%. The
      three phenotypes did not differ in mean body mass index, waist-to-hip ratio,
      racial composition, degree of oligo-ovulation, prevalence of acne, or family
      history of hyperandrogenic symptomatology. However, subjects demonstrating the
      Oligo+HA+Hirsutism phenotype were the youngest and had the greatest degrees of
      hyperandrogenemia, hyperinsulinemia, and beta-cell function; patients with the
      Oligo+Hirsutism phenotype where the oldest and had the mildest degrees of
      hyperandrogenemia, hyperinsulinemia, and beta-cell function. Subjects with the
      Oligo+HA phenotype demonstrated intermediate degrees of hyperandrogenemia and
      metabolic dysfunction. CONCLUSION(S): We conclude that the three clinical
      phenotypes of PCOS do not represent forms of the same metabolic disorder and may
      be the result of varying degrees of metabolic dysfunction; greater degrees of
      beta-cell function and circulating insulin levels favored the development of
      hirsutism and frank hyperandrogenemia.

PMID- 15950642
TI  - Androgen receptor gene CAG length polymorphism in women with polycystic ovary
      syndrome.
AB  - OBJECTIVE: To determine whether the CAG repeat length of the androgen receptor
      (AR) gene contributes to individual differences in the susceptibility to the
      development of polycystic ovary syndrome (PCOS). DESIGN: Retrospective case
      control study. SETTING: University-based clinic. PATIENT(S): One hundred six
      nondiabetic women with PCOS and 112 nonhirsute fertile controls. INTERVENTION(S):
      Androgen receptor gene CAG repeat length was analyzed in women with PCOS and
      their controls. MAIN OUTCOME MEASURE(S): Androgen receptor gene CAG repeat length
      in both groups. RESULT(S): The mean CAGn was 21.5 repeats in both groups (NS; t
      test). Furthermore, when the CAGn lengths were divided into three categories
      (CAGn < or =18, 19-24, > or =25), the distribution was similar in both groups
      (NS; chi2 test). However, all five women carrying < or =15 CAG repeats belonged
      to the PCOS group. In the PCOS group, CAGn did not correlate with body mass index
      or serum testosterone concentration. CONCLUSION(S): Androgen receptor CAGn is not
      a major determinant of PCOS. However, it may be a significant modulator of
      androgen-related diseases in some individuals.

PMID- 15950643
TI  - Long-term follow-up after conservative surgery for bladder endometriosis.
AB  - OBJECTIVE: To describe the long-term outcome of surgical conservative treatment
      of bladder endometriosis. DESIGN: Descriptive study. SETTING: Tertiary referral
      center for the treatment of endometriosis. PATIENT(S): Forty-seven patients with
      symptomatic bladder endometriosis. INTERVENTION(S): Partial cystectomy by
      laparoscopy or laparotomy. MAIN OUTCOME MEASURE(S): Rates of recurrence at a 36
      month follow-up. RESULT(S): All 14 patients with isolated bladder dome lesions
      remained symptom-free. Among the 33 patients with lesions involving the vesical
      base and vesicouterine septum, cumulative recurrence rates at 36 months were
      24.7% and 15.5% for recurrence of symptoms and of clinical-instrumental evidence
      of lesion, respectively. The only factor influencing rate of recurrence was the
      extent of surgical excision. When the resection included both the vesical lesion
      and a 0.5- to 1-cm deep portion of the adjacent myometrium, recurrence was
      significantly less frequent compared to the removal of the bladder lesion only
      (7% vs. 37% for symptom recurrence and 0% vs. 26% for clinical-instrumental
      recurrence, respectively). CONCLUSION(S): Conservative surgical treatment of
      bladder endometriosis seems effective in ensuring long-term relief in almost all
      cases of endometriosis affecting the vesical dome, whereas success rates for
      deeper lesions involving the vesical base and the vesicouterine septum are lower,
      depending on the degree of surgical radicality.

PMID- 15950644
TI  - Assessing the emotional needs of women with spontaneous premature ovarian
      failure.
AB  - OBJECTIVE: To examine women's emotional responses to learning the diagnosis of
      premature ovarian failure (POF) and identify the sources of support used for
      coping. DESIGN: Observational study. SETTING: National Institutes of Health
      Clinical Center. PATIENT(S): One hundred women previously diagnosed with POF of
      median age 28 years at diagnosis. INTERVENTION(S): Structured telephone
      interviews based on focus group findings. MAIN OUTCOME MEASURE(S): Manner
      informed of POF diagnosis, emotional response, and areas of emotional support.
      RESULT(S): Overall, 71% were unsatisfied with the manner in which they were
      informed by their clinician, and 89% reported experiencing moderate to severe
      emotional distress at the time. The degree of emotional distress was positively
      correlated with the degree of dissatisfaction with the manner in which the women
      had been informed of the diagnosis. Thorough and accurate medical information on
      POF, support of others, and spirituality were perceived as helpful in coping.
      CONCLUSION(S): Learning the diagnosis of POF can be emotionally traumatic and
      difficult for women. The findings suggest that the manner in which patients are
      informed of this diagnosis can significantly impact their level of distress.
      Patients perceive a need for clinicians to spend more time with them and provide
      more information about POF.

PMID- 15950645
TI  - Prevalence of premature urinary luteinizing hormone surges in women with regular
      menstrual cycles and its effect on implantation of frozen-thawed embryos.
AB  - OBJECTIVE: To determine the frequency and effect of premature luteinizing hormone
      (LH) surges on pregnancy rates in women with regular menstrual cycles. DESIGN:
      Retrospective cohort study. SETTING: Assisted Reproductive Technology Program at
      private medical college. PATIENT(S): Regularly menstruating women undergoing
      frozen embryo transfer (ET). INTERVENTION(S): Detection of urinary LH surges with
      an RIA kit during natural-cycle frozen-embryos transfer. MAIN OUTCOME MEASURE(S):
      Incidence of premature LH surges and pregnancy outcomes. RESULT(S): Eighty-eight
      (46.8%) of 188 regularly menstruating women had premature LH surges and 33 (37%)
      of those 88 had multiple premature LH surges. Pregnancy rates per ET are similar
      between women with and without premature LH surges. CONCLUSION(S): A high
      percentage of normally cycling women demonstrate premature urinary LH surges
      without an effect on outcome of frozen-thawed ETs.

PMID- 15950646
TI  - Infertility-related stress in men and women predicts treatment outcome 1 year
      later.
AB  - OBJECTIVE: To examine the separate and joint effects of male and female fertility
      problem (FP) stress and the source of stress (e.g., personal, social, marital) on
      treatment outcome. DESIGN: Prospective, epidemiological cohort design. SETTING:
      Fertility clinics in Denmark. PATIENT(S): Eight hundred eighteen couples who were
      about to begin a new course of treatment. INTERVENTION(S): An FP stress inventory
      was administered at the start of treatment, and the treatment outcome was
      evaluated 12 months later. MAIN OUTCOME MEASURE(S): Number of treatment cycles in
      12-month study period and treatment outcome (i.e., success, no success).
      RESULT(S): Fertility problem stress was associated with a poorer treatment
      outcome in women (pooled within-groups [WGr] correlation,WGr = .517) and men (WGr
      = .392) with the effect significantly more pronounced for women (z = 3.19,
      P<.001). Fertility problem stress arising in the personal and marital domain
      showed greater associations with treatment outcome than did FP stress from the
      social domain. Logistic regression indicated that women who reported more marital
      distress required more treatment cycles to conceive (median 3) than women
      reporting less marital distress (median 2) (odds ratio [OR] = 1.20: Model chi2(3)
      = 77.21, P<.001). CONCLUSION(S): The findings provide evidence that infertility
      related stress has direct and indirect effects on treatment outcome.

PMID- 15950647
TI  - Thyroid function after assisted reproductive technology in women free of thyroid
      disease.
AB  - OBJECTIVE: To evaluate thyroid function in women undergoing a first assisted
      reproductive technology (ART) procedure and to compare women with ongoing
      pregnancy or miscarriage. DESIGN: Prospective cohort study. SETTING: Tertiary
      referral center. PATIENT(S): Seventy-seven women free of thyroid disease.
      INTERVENTION(S): Serum TSH and FT4 were determined before and 2, 4, and 6 weeks
      after ET. All women received the same ART protocol. MAIN OUTCOME MEASURE(S):
      Thyroid function. RESULT(S): Forty-five women had ongoing pregnancies, and 32
      suffered a miscarriage after 6.7 weeks (range 5-11). Mean age and number of ET
      were similar in both groups. Compared with baseline values, TSH and FT4 increased
      significantly 2 weeks after ET (ongoing pregnancies group: TSH 2.5 +/- 1.3 vs.
      1.6 +/- 0.8 mU/L and FT4 13.8 +/- 1.4 vs. 12.4 +/- 1.8 ng/L; miscarriage group:
      TSH 2.1 +/- 1.0 vs. 1.5 +/- 0.7 mU/L and FT4 14.2 +/- 2.0 vs. 12.4 +/- 1.9 ng/L).
      Pregnancy outcome did not affect thyroid function and its evolution over time.
      CONCLUSION(S): In women free of thyroid diseases, thyroid function changed
      significantly after ART, but these changes were not different between women with
      ongoing pregnancy and miscarriage.

PMID- 15950648
TI  - Inhibin A and activin A may be used to predict pregnancy outcome in women with
      recurrent miscarriage.
AB  - OBJECTIVE: To look at the role of inhibin and activin in predicting pregnancy
      outcome in patients with history of recurrent miscarriage. DESIGN: Observational
      clinical study. SETTING: Recurrent miscarriage clinic of a tertiary care teaching
      hospital. PATIENT(S): Patients with history of recurrent miscarriage.
      INTERVENTION(S): Serial serum inhibin A and activin A concentrations were
      measured in weeks 5 though 8 of pregnancy. MAIN OUTCOME MEASURE(S): Serum
      concentrations of inhibin A and activin A levels. RESULT(S): Mean inhibin A
      concentration at 5 to 6 weeks for women who miscarried and those who had live
      births was 33 and 51 pg/mL, respectively; activin A at same gestation for the two
      groups was 534 and 643 pg/mL, respectively. After 2 weeks, mean inhibin A
      concentration for women who miscarried and those who had live births was 66 and
      145 pg/mL, respectively, and activin A was 747 and 1,123 pg/mL, respectively.
      CONCLUSION(S): It is possible that inhibin A and activin A may be used as markers
      to predict pregnancies that are likely to miscarry.

PMID- 15950649
TI  - A new method for estimating the effectiveness of emergency contraception that
      accounts for variation in timing of ovulation and previous cycle length.
AB  - OBJECTIVE: To develop a new method for estimating the effectiveness of emergency
      contraception (EC) by using information about previous menstrual cycle length,
      accounting for the variation in the day of ovulation within the menstrual cycle,
      and comparing the validity of the new and previous methods. METHOD(S): Secondary
      analysis of a data set with a biological marker of ovulation and its distribution
      in the cycle. Based on a sample of cycles with known length and a known
      biological marker of ovulation, we simulated trials of predetermined EC
      effectiveness and then calculated estimates of EC effectiveness based on old and
      new methods. RESULT(S): Under some conditions, all methods produced biased
      estimates of effectiveness with simulated trials, especially when the actual
      effectiveness was low. The systematic bias was minimized with the new method. The
      new method was robust with regard to the distribution of the day of intercourse
      in women presenting for EC. CONCLUSION(S): Future studies of EC effectiveness
      should consider both the uncertainty in predicting the day of ovulation and
      previous cycle length. Our estimates of daily fecundity should be replicated with
      other data sets.

PMID- 15950650
TI  - Hormone therapy use among postmenopausal French women before the publication of
      the Women's Health Initiative study: duration of use and factors associated with
      discontinuation.
AB  - OBJECTIVE: Compliance with recent recommendations concerning hormone therapy (HT)
      requires that we understand the reasons why women receiving HT continue or stop
      their treatment. Our aim was to estimate the duration of HT use and analyze
      factors associated with its discontinuation during the period before the
      publication of articles challenging the safety of HT. DESIGN: With data from 3
      mail questionnaires--at inclusion (in 1990), 3 years, and 6 years--we estimated
      the cumulative treatment continuation rate by the actuarial method and used the
      Cox model to analyze the factors associated with discontinuation. SETTING: French
      women participating in the GAZEL cohort of employees of the French national power
      and electricity company (Electricite de France-Gaz de France). PATIENT(S): One
      thousand eighty-three postmenopausal women who were ever-HT users.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Discontinuation of HT. RESULT(S):
      A total of 91.6% of women consulted gynecologists, and 88% continued treatment 5
      years after they had begun it. Those reporting hot flashes as a reason for taking
      HT and those younger than 45 years old at menopause were less likely to stop HT,
      as were women reporting alcohol use. CONCLUSION(S): Our results demonstrate the
      importance of providing information to physicians, primarily gynecologists, to
      ensure appropriate treatment of symptoms for menopausal women, especially those
      younger than 45 years old, while bearing their long-term health in mind.

PMID- 15950651
TI  - Binding of recombinant human proacrosin/acrosin to zona pellucida (ZP)
      glycoproteins. I. Studies with recombinant human ZPA, ZPB, and ZPC.
AB  - OBJECTIVE: To characterize proacrosin/acrosin interaction with isolated zona
      pellucida (ZP) components. DESIGN: Prospective study. SETTING: Basic research
      laboratory. PATIENT(S): Recombinant proteins derived from human proacrosin (Rec
      40, Rec-30, Rec-20, Rec-10, and Rec-6) and from human ZP glycoproteins (rec-hZPA,
      ZPB, and ZPC). INTERVENTION(S): In vitro binding assay developed to assess
      proacrosin/acrosin-ZP interaction. MAIN OUTCOME MEASURE(S): Zona pellucida
      glycoprotein binding to proacrosin/acrosin; estimation of binding affinity.
      RESULT(S): Of all ZP proteins, rec-hZPA demonstrated the highest binding activity
      toward acrosin (Rec-30) (rec-hZPB: 42% of rec-hZPA; rec-hZPC: 39% of rec-hZPA;
      P<.0005). Rec-hZPA interaction was disturbed by dextran sulphate (75% inhibition
      with 10 microM), fucose (67% inhibition with 1.5 microM), and mannose (69%
      inhibition with 333 mM). Comparing binding activity of proacrosin with other N
      terminal acrosin fragments, Rec-40 showed 2.6-3 times higher levels. Moreover,
      saturable high affinity binding of Rec-40 to ZP components was observed (Kd: 34
      nM for rec-hZPA, 38 nM for rec-hZPB, 63 nM for rec-hZPC). CONCLUSION(S): The rec
      hZPA is the major ZP ligand for human proacrosin/acrosin. The interaction
      involves mannosyl, fucosyl, and sulfated glycans. Binding sites for rec-hZP would
      be located both at the N- and C-terminus of proacrosin, revealing a key role of
      the proenzyme in the interaction.

PMID- 15950652
TI  - Binding of recombinant human proacrosin/acrosin to zona pellucida glycoproteins.
      II. Participation of mannose residues in the interaction.
AB  - OBJECTIVE: To assess the interaction of human proacrosin/acrosin with mannose
      residues coupled to a protein backbone. DESIGN: Prospective study. SETTING: Basic
      research laboratory. PATIENT(S): Recombinant proteins derived from human
      proacrosin (Rec-40, Rec-30, Rec-20, Rec-10, and Rec-6) and bovine serum albumin
      (BSA)-mannose as ligand. INTERVENTION(S): In vitro binding assay developed to
      assess proacrosin/acrosin-BSA-mannose interaction. MAIN OUTCOME MEASURE(S):
      Proacrosin/acrosin binding to BSA-mannose; estimation of binding affinity.
      RESULT(S): All recombinant proteins of acrosin but Rec-6 (residues 1-59 of
      proacrosin) specifically bound to BSA-mannose. Rec-40 (proacrosin) showed the
      highest binding affinity (dissociation constant K(d), 162 nM), followed by N
      terminal fragments Rec-30 (248 nM), Rec-20 (359 nM), and Rec-10 (402 nM). A
      significant decrease in binding activity was observed when acrosin proteins were
      treated with denaturing agents such as urea or heat. The beta-mercaptoethanol
      treatment produced a 39% decrease on Rec-30 binding to BSA-mannose; in contrast,
      no effect was observed with Rec-40, suggesting the presence of at least two types
      of mannose-binding sites. CONCLUSION(S): [1] Proacrosin interacts with mannose
      residues through binding sites located at both the N- and C-terminal portion of
      the protein, [2] the full-length protein is required for maximal BSA-mannose
      binding, and [3] binding sites are stabilized by noncovalent bonds and by
      disulfide linkages.

PMID- 15950653
TI  - The aromatase inhibitor anastrozole is associated with favorable embryo
      development and implantation markers in mice ovarian stimulation cycles.
AB  - OBJECTIVE: To investigate the embryonic and endometrial effects of anastrozole in
      preimplantation and implantation phases in FSH-induced cycles in mice. DESIGN:
      Blind randomized study. SETTING: University research laboratory. ANIMAL(S):
      Twenty-seven mature female mice. INTERVENTION(S): Single-dose anastrozole (25
      mg/kg [0.75 mg]), recombinant FSH (5 IU/mL), and hCG (5 IU/mL) (n = 9);
      recombinant FSH (5 IU/mL) and hCG (5 IU/mL) (n = 9); or sterile saline (1 mL) (n
      = 9). The morning of finding the vaginal plug was designated as day 1 of
      embryonic development (E1). Three mice from each group were sacrificed on E1 and
      embryos aspirated from uterine tubes. The rest of the mice were sacrificed on
      E2.5-3 and uteruses removed. MAIN OUTCOME MEASURE(S): Embryo quality, endometrial
      histologic evaluation, and immunohistochemical analysis of tumor necrosis factor
      alpha, leukemia inhibitory factor, laminin, and collagen IV staining. RESULT(S):
      Anastrozole use in FSH-induced cycles not only caused an increase in
      preimplantation receptivity and implantation but also supported release of
      implantation markers. The enhanced embryo development seen in this study would
      explain the higher implantation because embryo development is synchronized with
      endometrial development. CONCLUSION(S): In mice, the use of anastrozole in FSH
      induced cycles has a positive effect on embryo quality and implantation. This
      effect might be species dependent, and human studies are needed.

PMID- 15950654
TI  - Expression and immunolocalization of the calpain-calpastatin system in the human
      oocyte.
AB  - OBJECTIVE: To investigate the expression of the calpain-calpastatin system in the
      human oocyte. DESIGN: The expression of the calpain-calpastatin system was
      determined by immunohistochemistry and immunoblot analysis. SETTING: Academic
      research laboratory. PATIENT(S): Twenty Israeli women who underwent IVF for
      fertility problems. INTERVENTION(S): Oocytes that had no pronuclei 24 hours after
      insemination by either conventional IVF or intracytoplasmic sperm injection were
      retrieved for the study. MAIN OUTCOME MEASURE(S): Analysis of calpain isoforms
      (m, mu) and calpastatin distribution within the human oocyte. RESULT(S): Western
      blot analysis confirmed the expression of calpain and calpastatin.
      Immunohistochemistry of fixed, permeabilized oocytes exhibited localization of
      both calpains to the cortical region of the oocyte, as well as the cytosol.
      Calpastatin seemed to be distributed throughout the cytosol, with a marked
      accumulation in the cell membrane. We have demonstrated a negative correlation
      between the occurrence of cortical granule exocytosis and the stability of the
      metaphase plate. CONCLUSION(S): A complete calpain-calpastatin system is
      expressed in the human oocyte and might play a role in the various calcium
      mediated processes occurring during activation of human oocytes.

PMID- 15950655
TI  - Lipiodol alters murine uterine dendritic cell populations: a potential mechanism
      for the fertility-enhancing effect of lipiodol.
AB  - OBJECTIVE: To determine whether treatment with lipiodol alters the leukocyte
      population in the uterus. DESIGN: Randomized controlled animal study. SETTING:
      University research laboratory. ANIMAL(S): Sixty female Swiss white mice at
      proestrous. INTERVENTION(S): Infusion of the female reproductive tract with
      lipiodol versus infusion with saline versus sham treatment. MAIN OUTCOME
      MEASURE(S): Counts of uterine macrophages, dendritic cells, and total leukocytes
      assessed by immunohistochemistry. RESULT(S): No statistically significant
      differences were found in the mean number of total leukocytes or macrophages
      between the three treatment groups. The mean number of CD205+ dendritic cells
      showed a statistically significant decrease following lipiodol treatment compared
      with the sham treatment and saline treatment. The mean number of CD1+ dendritic
      cells showed a statistically significant increase following lipiodol treatment
      compared with the sham treatment. CONCLUSION(S): Intrauterine lipiodol infusion
      is associated with a change in the uterine dendritic cell populations in mice.
      This change may alter the uterine immune response to the fetus, leading to
      improved fertility.

PMID- 15950657
TI  - A randomized trial of excision versus ablation for mild endometriosis.
AB  - OBJECTIVE: To compare excisional and ablative treatment modalities for mild
      (revised American Fertility score 1-2) endometriosis in the management of chronic
      pelvic pain. DESIGN: A randomized study of excision or ablation for mild
      endometriosis, participants and investigators alike blinded to the treatment
      modality at the follow-up visit. SETTING: District general hospital with a
      specialist pelvic pain clinic in the United Kingdom. PATIENT(S): Women presenting
      with chronic pelvic pain. INTERVENTION(S): Participants were asked to complete a
      questionnaire detailing symptoms related to chronic pelvic pain and rating their
      pain on a ranked ordinal scale. Areas of pelvic tenderness were identified and
      similarly ranked. At laparoscopy they were randomly assigned to excision or
      ablation of any endometriotic lesions, and the questionnaire was repeated at 6
      months. MAIN OUTCOME MEASURE(S): Changes in pain score on a ranked ordinal scale
      after surgical treatment for mild endometriosis. RESULT(S): Both treatment
      modalities produced good symptomatic relief and reduction of pelvic tenderness
      (67%). There was no difference in morbidity; one woman in each group became
      pregnant during the study period. Only two participants reported no relief or a
      worsening of symptoms or signs. CONCLUSION(S): This small study showed good
      symptom relief at 6 months from pelvic pain for the majority of participants
      irrespective of the treatment modality, but two participants did not improve or
      got worse. A high pain score before treatment was a predictor of appreciable
      improvement. Further work is needed to identify women in whom surgical
      intervention is likely to produce a good response.

PMID- 15950656
TI  - Raloxifene promotes prostacyclin release in human endothelial cells through a
      mechanism that involves cyclooxygenase-1 and -2.
AB  - OBJECTIVE: To examine the effects of raloxifene on prostacyclin production by
      human umbilical vein endothelial cells (HUVEC) and to shed light on the molecular
      details of that action. DESIGN: Cell culture for 4, 8, 16, 24, and 48 hours.
      SETTING: University research laboratory. PATIENT(S): Source of HUVEC.
      INTERVENTION(S): Measurement of prostacyclin production and of protein levels and
      mRNA expression of cyclooxygenase (COX)-1 and -2. MAIN OUTCOME MEASURE(S):
      Prostacyclin production was measured by enzyme immunoassay, the mRNA expression
      of COX-1 was measured by quantitative real time-polymerase chain reaction, and
      the protein levels of COX-1 and -2 were measured by immunoblotting. RESULT(S):
      Raloxifene significantly increased prostacyclin release in a time- and dose
      dependent manner, being higher than control after 24 hours. Raloxifene, at 0.1-10
      nM, increased the mRNA expression of COX-1 and the protein content of both COX-1
      as well as COX-2. All of these effects were independent of the classical pathway
      for estrogen receptor (ER) activation because the treatment of cells with the ER
      antagonist ICI 182780 did not eliminate any of the effects. Although treatment
      with either the selective COX-1 inhibitor SC-560 or the selective COX-2 inhibitor
      NS-398 significantly diminished prostacyclin release (20% +/- 5% and 24% +/- 7%,
      respectively), co-treatment with raloxifene and either SC-560 or NS-398 was
      followed by a smaller increase than that achieved by raloxifene alone. The
      nonselective COX inhibitor indomethacin, however, reduced prostacyclin production
      to 37% +/- 11% of control values. CONCLUSION(S): Raloxifene increased HUVEC
      prostacyclin release through a mechanism possibly distinct from the classical ER
      pathway and involving enhanced COX-1 and COX-2 expression and activity.

PMID- 15950658
TI  - Use of the potassium titanyl phosphate laser in the laparoscopic anterior rectum
      slicing operation.
AB  - OBJECTIVE: To evaluate the efficacy of the potassium titanyl phosphate (KTP)
      laser used during the laparoscopic anterior rectum slicing (LARS) operation.
      DESIGN: Retrospective study. SETTING: National Hospital Organization Kyoto
      Medical Center, Kyoto, Japan. PATIENT(S): All 46 patients who underwent the LARS
      operation using the KTP laser. INTERVENTION(S): The LARS operation using the KTP
      laser for treatment of deep rectal endometriosis. MAIN OUTCOME MEASURE(S):
      Operative and postoperative outcome. RESULT(S): Meaningful improvements in
      clinical symptoms were obtained with the LARS operation using the KTP laser with
      acceptable levels of postoperative morbidity. Bowel leakage did not occur in any
      of the patients. CONCLUSION(S): Deep rectal endometriosis can be treated
      effectively with the LARS operation using the KTP laser.

PMID- 15950659
TI  - Abdominal myomectomy after failed uterine artery embolization.
AB  - OBJECTIVE: Report a case of a difficult myomectomy after a failed uterine artery
      embolization (UAE). DESIGN: Case report. SETTING: A university medical center.
      PATIENT(S): A 30-year-old woman with pelvic pain and menorrhagia secondary to an
      enlarging 18- to 20-week-size fibroid uterus. INTERVENTION(S): Abdominal
      myomectomy. MAIN OUTCOME MEASURE(S): Complicated myomectomy after UAE. RESULT(S):
      A patient underwent a difficult myomectomy after failed UAE. The myomectomy was
      only partially completed due to the difficult dissection of the myomas.
      CONCLUSION(S): Myomectomy after UAE may be unusually difficult due to the
      degenerative changes that occur within the leiomyomas.

PMID- 15950660
TI  - Placement of a Malecot catheter to enable embryo transfer after radical
      trachelectomy.
AB  - OBJECTIVE: To describe the use of a Malecot catheter as a stent after radical
      trachelectomy (RT). DESIGN: Case report. SETTING: Assisted conception unit at a
      teaching hospital in the United Kingdom. PATIENT(S): A 36-year-old woman
      undergoing IVF after her cervix had been excised for cervical carcinoma. Previous
      attempts at embryo transfer (ET) had been very traumatic and required a
      transmyometrial transfer on one occasion. INTERVENTION(S): A Malecot catheter was
      inserted into the uterine cavity after a dilatation procedure had been performed
      and removed before ovarian stimulation. MAIN OUTCOME MEASURE(S): Ease of ET.
      RESULT(S): The subsequent ET was much more straightforward. CONCLUSION(S): This
      technique can facilitate ET after RT if the passage is found to be stenosed.

PMID- 15950661
TI  - Laparoscopic retrieval of retroperitoneal vas deferens in vasovasostomy for
      postinguinal herniorrhaphy obstructive azoospermia.
AB  - OBJECTIVE: Iatrogenic injury to the vas deferens is a well-documented
      complication of inguinal hernia repair. Recently obstruction related to the use
      of polypropylene mesh for hernia repair has been reported. We describe a case
      using laparoscopy to mobilize the retroperitoneal vas and deliver it to the
      healthy vas proximal to the vas trapped in the cicatrix induced by mesh thus
      allowing a tension-free microsurgical repair. DESIGN: Case report. SETTING:
      Outpatient male infertility practice. PATIENT(S): Obstructed azoospermic men with
      polypropylene mesh. INTERVENTION(S): Laparoscopic retrieval of retroperitoneal
      vas segment for primary microsurgical anastomosis. MAIN OUTCOME MEASURE(S):
      Patency of vas and presence of sperm. RESULT(S): A tension-free, patent
      anastomosis was performed. CONCLUSION(S): Polypropylene mesh-induced fibrosis of
      the vas deferens can result in obstructive azospermia. Laparoscopy can be used to
      permit a microsurgical bypass of the obstructed segment.

PMID- 15950662
TI  - Mutational analysis of the homeobox region of the human NOBOX gene in Japanese
      women who exhibit premature ovarian failure.
AB  - To determine whether mutations of the homeobox region of the human NOBOX gene are
      present in Japanese women with premature ovarian failure (POF), genomic DNA of
      blood samples from 30 women with POF and 20 normal controls were extracted for
      polymerase chain reaction (PCR) and analyzed by direct sequencing. No mutations
      in exons 2-6 of the NOBOX gene, including the homeobox region, could be
      identified in Japanese women with POF. Our data suggest that mutations of the
      homeobox region of the NOBOX gene are uncommon in Japanese patients with POF.

PMID- 15950663
TI  - Aneuploid analysis of tripronuclear zygotes derived from in vitro fertilization
      and intracytoplasmic sperm injection in humans.
AB  - This study demonstrates that the diploid ratio of tripronuclear zygotes after
      intracytoplasmic sperm injection (ICSI) is significantly higher as compared with
      that after conventional IVF; the extra pronucleus of tripronuclear zygotes after
      ICSI are mostly from the second polar body, not from sperm.

PMID- 15950664
TI  - Promising results with 306 single blastocyst transfers.
AB  - Single blastocyst transfer was performed in 306 IVF patients during 2002 to
      August 2003 in women younger than 39 years of age with at least five fertilized
      oocytes. Viable pregnancy rate per single blastocyst transfer was 40.7% during
      2002 and 47.6% during 2003 (amounting to 35% of all IVF cycles), which in our
      experience are acceptable results.

PMID- 15950665
TI  - Growth hormone secretion and insulin-like growth factor-1 are related to
      hyperandrogenism in nonobese patients with polycystic ovary syndrome.
AB  - Women of normal weight with polycystic ovary syndrome (PCOS) and hyperinsulinemia
      presented high growth hormone (GH) levels in response to the l-dopa test,
      suggesting that the action of GH and insulin-like growth factor-1 (IGF-1) might
      be responsible for the elevation in LH and the consequent hyperandrogenic
      anovulation observed in normal weight women with PCOS. Insulin resistance and
      obesity are related to a reduction in GH secretion in obese women with PCOS.

PMID- 15950666
TI  - Differentiating between primary and secondary Sertoli-cell-only syndrome by
      histologic and hormonal parameters.
AB  - The contribution of histologic differentiation between primary and secondary
      Sertoli-cell-only (SCO) syndrome in azoospermic men was evaluated. No correlation
      was found between the presence of sperm cells in the testis and the histologic
      findings or inhibin B or FSH levels, suggesting a low prognostic value for this
      differentiation.

PMID- 15950667
TI  - Endometrial effects, bleeding control, and compliance with a new postmenopausal
      hormone therapy regimen based on transdermal estradiol gel and every-other-day
      vaginal progesterone in capsules: a 3-year pilot study.
AB  - In a 3-year prospective study, 30 postmenopausal women received transdermal E2
      gel and every-other-day vaginal P in capsules. At study completion, endometrial
      thickness was significantly reduced as compared with baseline (2.7 +/- 0.5 vs.
      3.4 +/- 0.9 mm), endometrial biopsy showed endometrial atrophy in all cases, and
      amenorrhea was achieved in 92.6% of cycles, while excellent patient satisfaction
      was achieved.

PMID- 15950668
TI  - Long-term use of oral contraceptives increases the risk of miscarriage.
AB  - In this prospective, case-control study, a step-wise logistic regression model
      was used to examine the relationship between the consumption of oral
      contraceptives before pregnancy and the potential increase in the risk of
      miscarriage. Consumption of oral contraceptives for more than 2 years before
      pregnancy is associated with a higher risk of miscarriage.

PMID- 15950669
TI  - Role of intratesticular ultrasonographic and Doppler flow analyses in evaluating
      gonadal status in male survivors of childhood malignancy.
AB  - Fifty-seven males, previously treated for malignancies in childhood, and who
      refused to masturbate for semen analysis, were submitted to hormonal,
      ultrasonographic, and Doppler evaluation to assess the effects of
      chemotherapy/radiotherapy on gonadal function. Nineteen normal healthy fertile
      males served as controls. In the studied population, FSH was inversely correlated
      with testicular volume and directly correlated with testicular vascularization,
      suggesting that ultrasonographic and color Doppler scanning of the testes may be
      used, if a sperm count is not available, to indirectly assess the gonadal
      function.

PMID- 15950670
TI  - Adhesion formation and interanimal variability in a laparoscopic mouse model
      varies with strains.
AB  - Adhesion formation after laparoscopic surgery was evaluated in mice of different
      strains. More adhesions were observed in Swiss, NMRI, and BALB/c mice, with less
      interanimal variability in BALB/c mice. These data point to genetics effects on
      adhesion formation, which open new insights in its pathogenesis and indicate the
      importance of a careful strain selection for animal studies.

PMID- 15950671
TI  - Suppression of estrogen-withdrawal headache with extended transdermal
      contraception.
AB  - A randomized clinical trial was conducted with 239 women at nine clinical
      research sites to compare bleeding profile, headache frequency, and subject
      satisfaction with the transdermal contraceptive, ORTHO EVRA
      (norelgestromin/ethinyl estradiol transdermal system) used in an extended regimen
      (84 days) with a traditional, 28-day cyclic regimen. In a majority of women
      studied, compared with cyclic use, extended use of transdermal
      norelgestromin/ethinyl estradiol delayed menses and reduced the total incidence
      of mean headache days during the hormone-free interval.

PMID- 15950673
TI  - Depression in primary versus secondary infertility egg recipients.
AB  - Women with primary infertility and their husbands were significantly more
      depressed than women with secondary infertility and their husbands, and the
      difference in levels of depression of women compared with their husbands was
      significantly greater for primary than for secondary infertility. Depressive
      symptomology for childless individuals is greater for wives than for their
      husbands.

PMID- 15950672
TI  - Expression and regulation of CCR1 in peritoneal macrophages from women with and
      without endometriosis.
AB  - CCR1 is a CC chemokine receptor with high affinity for RANTES (regulated upon
      activation, normal T cells expressed and secreted). CCR1 protein and mRNA
      concentrations in native peritoneal cells were twofold greater, in cultured
      peritoneal cells threefold greater, in patients with endometriosis compared to
      patients without endometriosis, as determined by Western blotting fluorescence
      activated cell sorting analysis, reverse transcription-polymerase chain reaction,
      and in situ hybridization.

PMID- 15950675
TI  - The precision of assays for serum insulin?

PMID- 15950677
TI  - The intangible female factor affecting the success of vasovasostomy?

PMID- 15950678
TI  - Prenatal diagnosis for late-onset disease--always room for discussion.

PMID- 15950679
TI  - Prediction models for high-order multiple pregnancy.

PMID- 15950681
TI  - Endometrial dating--still room for controversy.

PMID- 15950685
TI  - Degenerative disorders of the lumbar and cervical spine.
AB  - Degenerative disorders in the spine are normal, age-related phenomena and largely
      asymptomatic in most cases. Conservative management of lumbar and cervical
      spondylosis is the mainstay of treatment, and most patients with symptomatic
      degenerative changes respond appropriately with nonsurgical management. Surgical
      intervention can be considered an appropriate and viable option when conservative
      measures have failed. Treatment options should always be directed toward the
      specific nature and location of the patient's individual pathology. Although
      current standards in the surgical management of lumbar and cervical degenerative
      disorders include discectomy, neural decompression, and instrumented spinal
      arthrodesis, new approaches that address this often-challenging clinical entity
      are on the horizon.

PMID- 15950686
TI  - Advantages and disadvantages of nonfusion technology in spine surgery.
AB  - Nonfusion technology in spine surgery may improve outcomes by reducing surgical
      morbidity and the incidence of adjacent level degeneration; however, new
      technologies also introduce new short- and long-term complications. There is
      currently no evidence that nonfusion implants are superior to fusion in mid- to
      long-term follow-up. Understanding the potential risks and benefits of nonfusion
      technology is essential for spine surgeons and their patients. This article
      reviews the current evidence relating to the potential risks and benefits of
      nonfusion technology in spine surgery.

PMID- 15950687
TI  - Biomechanics of nonfusion implants.
AB  - Although spine fusion is a versatile and effective technique in the treatment of
      spinal disorders, increased stresses on adjacent unfused levels lead to
      symptomatic adjacent level degeneration in many patients. The goal of nonfusion
      devices in spine surgery is to ablate or unload painful structures while
      preserving segmental motion. The intended performance of nonfusion devices such
      as disc replacement, nucleus pulposus replacement, and posterior stabilization
      devices can be understood from the biomechanics of the functional spinal unit in
      health and disease and the interplay between the motion segment and the device.
      Implant design issues can also markedly affect performance.

PMID- 15950688
TI  - Standard and minimally invasive approaches to the spine.
AB  - With the advent of minimally invasive surgical approaches to the spine, the
      ability to adequately expose the desired anatomic structures while minimizing the
      disadvantages of excessive soft tissue stripping, dissection, and prolonged
      retraction has become increasingly popular. A minimally invasive one- or two
      level posterior exposure of the spine is now safely attainable with the latest
      minimal-access systems that exploit the biomechanics of an adjustable blade
      retractor. As the clinical use of these developing systems escalates, more
      outcomes data will become available to determine the safety and value of these
      minimally invasive procedures.

PMID- 15950689
TI  - Lumbar total disc replacement part I: rationale, biomechanics, and implant types.
AB  - Lumbar total disc replacement is an evolving new technology designed to preserve
      motion and to perhaps supplant fusion as the current "gold standard" surgical
      treatment for lumbar degenerative disc disease. Given the intense interest in
      disc replacement as a paradigm shift from fusion, this article describes the
      anatomy, physiology, and biomechanics of degenerative disc disease. Various
      treatment options and their outcomes are reviewed. A brief history of disc
      replacement surgery is outlined, current indications and commonly accepted
      contraindications for disc replacement surgery are explained, and current
      implants likely to be available in the United States are described. An overview
      of the surgical procedure is provided, with technical tips and pitfalls included.
      Finally, a standard postoperative regime is described.

PMID- 15950690
TI  - Clinical results of ProDisc-II lumbar total disc replacement: report from the
      United States clinical trial.
AB  - The much-awaited clinical use of lumbar artificial discs has begun in the United
      States. The United States Investigational Device Exemption (US IDE) clinical
      trial of the ProDisc-II prosthetic disc (Synthes, Paoli, PA) was recently
      completed, with all indications that it meets or surpasses the test of
      equivalence against fusion controls. This is a review of the clinical performance
      of the ProDisc-II artificial disc and includes an interim report from the US IDE
      trial at one site.

PMID- 15950691
TI  - Clinical results of Maverick lumbar total disc replacement: two-year prospective
      follow-up.
AB  - Disc prosthesis is the new treatment for degenerative disc disease in the lumbar
      spine. Key to assessing the interest in this new motion technique is evaluating
      the results in terms of functional and radiologic outcomes. This prospective
      study reports the outcome of 64 Maverick devices implanted between January 2002
      and November 2003. The degree of improvement was equivalent to that obtained with
      anterior fusion cages using the mini-invasive technique. Radiographic follow-up
      in this series showed a degree of mobility close to normal. The technique is safe
      because the intra- and postoperative complication rate is low. The Oswestry score
      improved for 75% of patients. This improvement is significantly correlated with
      facet arthrosis and muscle fatty degeneration.

PMID- 15950692
TI  - Clinical results of charite lumbar total disc replacement.
AB  - To preserve segmental lumbar motion and to prevent adjacent segment disease,
      there has been a growing enthusiasm for the use of intervertebral disc prosthesis
      as an alternative to segmental lumbar fusion. To date, more than 100-disc
      prostheses have been designed, but only 10 prostheses have been approved and
      implanted in humans. The Charite Artificial Disc has had the longest clinical
      follow-up with more than 5000 implantations in over 30 countries and reported >
      10-year satisfactory results.

PMID- 15950693
TI  - Lumbar partial disc replacement.
AB  - On the basis of the anatomy of the disc, the nucleus as pain generator and the
      resulting treatment possibility using nucleus replacement technologies are
      reviewed. Various devices are presented, from the first historical steps to
      treatment possibilities in the future. Clinical experiences of the widely-used
      PDN prosthetic device are analyzed.

PMID- 15950694
TI  - Cervical total disc replacement, part I: rationale, biomechanics, and implant
      types.
AB  - Cervical total disc replacement (TDR) is an attractive alternate to arthrodesis
      for management of disc degeneration and herniation in the cervical spine.
      Theoretic advantages of TDR include preservation of normal motion and
      biomechanics in the cervical spine and reduction of adjacent-segment
      degeneration. Other potential advantages include faster return to normal activity
      and elimination of the need for bone graft and associated donor site morbidity.
      This article introduces the rationale and various implant types available for
      cervical TDR. Part 2 of this series reviews the results and complications of
      specific implant designs.

PMID- 15950695
TI  - Cervical total disc replacement, part two: clinical results.
AB  - This article focuses on the clinical results of three prostheses (the Bryan
      Cervical Disc, the Bristol Disc, and the ProDisc-C) for cervical total disc
      replacement. Background on the development, design, and biomechanical
      characteristics of each prosthesis is given and surgical indications and clinical
      results are summarized and analyzed.

PMID- 15950696
TI  - Posterior dynamic stabilization systems: DYNESYS.
AB  - Posterior dynamic stabilization systems have to neutralize injurious forces and
      restore painless function of the spine segments and protect the adjacent
      segments. Because degenerative disc disease has many clinical manifestations,
      pedicular screw systems and interspinous implants have their indications. A
      dynamic stabilization device has to provide stability throughout its lifetime,
      unless it activates or allows reparative processes with a reversal of the
      degenerative changes. Anchorage to the bone is crucial, at least for pedicular
      systems. This is a great demand on spinal implants and assumes rest and motion
      going together. Our experience with DYNESYS has shown that this method has
      limitations in elderly patients with osteoporotic bone or in patients with a
      severe segmental macro-instability combined with degenerative olisthesis and
      advanced disc degeneration. Such cases have an increased risk of failure. Only
      future randomized evaluations will be able to address the potential reduction of
      accelerated adjacent segment degeneration. The few posterior dynamic
      stabilization systems that have had clinical applications so far have produced
      clinical outcomes comparable with fusion. No severe adverse events caused by
      these implants have been reported. Long-term follow-up data and controlled
      prospective randomized studies are not available for most of the cited implants
      but are essential to prove the safety, efficacy, appropriateness, and economic
      viability of these methods.

PMID- 15950697
TI  - Rationale, biomechanics, and surgical indications for Graf ligamentoplasty.
AB  - Graf ligamentoplasty stabilizes the unstable segment through coaptation of
      bilateral facet joints. Intervertebral disc height should be preserved to avoid
      postoperative neuroforaminal stenosis. Biomechanically and clinically, this
      procedure has the potential to treat "flexion instability" but cannot correct
      vertebral slippage or scoliotic deformity. Surgical indication or patient
      selection is the key to successful ligamentoplasty. The surgical indication is
      degenerative lumbar disorder with less than 25% of vertebral slip, minimal disc
      space narrowing, and coronal facet tropism. In the long-term, Graf
      ligamentoplasty may reduce the risk of adjacent-segment deterioration compared
      with spinal fusion.

PMID- 15950698
TI  - Hybrid constructs.
AB  - Hybrid constructs can combine motion-preserving technologies with each other or
      motion-preserving technologies with fusion techniques. Hybrid constructs can be
      implanted in single-stage or multistage surgeries. Early results are promising.
      Further study under formal scientific conditions is necessary to explore the
      benefit of these combinations.

PMID- 15950699
TI  - Complications and strategies for revision surgery in total disc replacement.
AB  - Spinal arthroplasty is an acceptable alternative to fusion in many cases of
      disabling degenerative disc disease. Although arthroplasty has been demonstrated
      to be a safe and efficacious surgical option, complications related to the
      approach or the device may occur in few cases. Revision strategies for failed
      total disc arthroplasty can be planned as a posterior fusion, leaving the total
      disc replacement device in place, or by way of anterior removal with subsequent
      anterior fusion or revision replacement of the prosthesis.

PMID- 15950700
TI  - Treatment of new-onset epilepsy: seizures beget discussion.

PMID- 15950701
TI  - Thyroid cancer after neck irradiation during childhood.

PMID- 15950702
TI  - Treating low back pain.

PMID- 15950703
TI  - Thomas Addison: one of the three "Giants" of Guy's Hospital.

PMID- 15950705
TI  - Do n-of-1 trials really tailor treatment?

PMID- 15950704
TI  - Curbing tobacco's toll starts with the professionals: World No Tobacco Day.

PMID- 15950707
TI  - Stress.

PMID- 15950708
TI  - Cutaneous melanoma.

PMID- 15950709
TI  - Cutaneous melanoma.

PMID- 15950712
TI  - Food for stroke: why don't the studies give clear answers?

PMID- 15950713
TI  - Conceiving and dying in Afghanistan.

PMID- 15950714
TI  - Immediate versus deferred antiepileptic drug treatment for early epilepsy and
      single seizures: a randomised controlled trial.
AB  - BACKGROUND: The relative risks and benefits of starting or withholding
      antiepileptic drug treatment in patients with few or infrequent seizures are
      unclear. We sought to compare policies of immediate versus deferred treatment in
      such patients and to assess the effects of these policies on short-term
      recurrence and long-term outcomes. METHODS: We undertook an unmasked,
      multicentre, randomised study of immediate and deferred antiepileptic drug
      treatment in 1847 patients with single seizures and early epilepsy. Outcomes
      comprised time to first, second, and fifth seizures; time to 2-year remission; no
      seizures between years 1 and 3 and between years 3 and 5 after randomisation; and
      quality of life. Analysis was by intention to treat. FINDINGS: 404 patients
      invited to join the trial did not consent to randomisation; 722 were subsequently
      assigned immediate treatment with antiepileptic drugs and 721 were assigned
      deferred treatment. Immediate treatment increased time to first seizure (hazard
      ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first
      tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2
      year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in
      the immediate treatment group and 77% of those in the deferred treatment group
      were seizure free between 3 and 5 years after randomisation (difference -0.2%
      [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality
      of life outcomes or serious complications. INTERPRETATION: Immediate
      antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2
      years, but does not affect long-term remission in individuals with single or
      infrequent seizures.

PMID- 15950715
TI  - Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer
      Survivor Study): a nested case-control study.
AB  - BACKGROUND: Survivors of malignant disease in childhood who have had radiotherapy
      to the head, neck, or upper thorax have an increased risk of subsequent primary
      thyroid cancer, but the magnitude of risk over the therapeutic dose range has not
      been well established. We aimed to quantify the long-term risk of thyroid cancer
      after radiotherapy and chemotherapy. METHODS: In a nested case-control study, 69
      cases with pathologically confirmed thyroid cancer and 265 matched controls
      without thyroid cancer were identified from 14,054 5-year survivors of cancer
      during childhood from the Childhood Cancer Survivor Study cohort. Childhood
      cancers were diagnosed between 1970 and 1986 with cohort follow-up to 2000.
      FINDINGS: Risk of thyroid cancer increased with radiation doses up to 20-29 Gy
      (odds ratio 9.8 [95% CI 3.2-34.8]). At doses greater than 30 Gy, a fall in the
      dose-response relation was seen. Both the increased and decreased risks were more
      pronounced in those diagnosed with a first primary malignant disease before age
      10 years than in those older than 10 years. Furthermore, the fall in risk
      remained when those diagnosed with Hodgkin's lymphoma were excluded. Chemotherapy
      for the first cancer was not associated with thyroid-cancer risk, and it did not
      modify the effect of radiotherapy. 29 (42%) cases had a first diagnosis of
      Hodgkin's lymphoma compared with 49 (19%) controls. 11 (42%) of those who had
      Hodgkin's lymphoma had subsequent thyroid cancers smaller than 1 cm compared with
      six (17%) of those who had other types of childhood cancer (p=0.07).
      INTERPRETATION: The reduction in radiation dose-response for risk of thyroid
      cancer after childhood exposure to thyroid doses higher than 30 Gy is consistent
      with a cell-killing effect. Standard long-term follow-up of patients who have had
      Hodgkin's lymphoma for detection of thyroid cancer should also be undertaken for
      survivors of any cancer during childhood who received radiotherapy to the thorax
      or head and neck region.

PMID- 15950716
TI  - Comparison of physical treatments versus a brief pain-management programme for
      back pain in primary care: a randomised clinical trial in physiotherapy practice.
AB  - BACKGROUND: Recommendations for the management of low back pain in primary care
      emphasise the importance of recognising and addressing psychosocial factors at an
      early stage. We compared the effectiveness of a brief pain-management programme
      with physiotherapy incorporating manual therapy for the reduction of disability
      at 12 months in patients consulting primary care with subacute low back pain.
      METHODS: For this pragmatic, multicentre, randomised clinical trial, eligible
      participants consulted primary care with non-specific low back pain of less than
      12 weeks' duration. They were randomly assigned either a programme of pain
      management (n=201) or manual therapy (n=201). The primary outcome was change in
      the score on the Roland and Morris disability questionnaire at 12 months.
      Analysis was by intention to treat. FINDINGS: Of 544 patients assessed for
      eligibility, 402 were recruited (mean age 40.6 years) and 329 (82%) reached 12
      month follow-up. Mean disability scores were 13.8 (SD 4.8) for the pain
      management group and 13.3 (4.9) for the manual-therapy group. The mean decreases
      in disability scores were 8.8 (6.4) and 8.8 (6.1) at 12 months (difference 0 [95%
      CI -1.3 to 1.4], p=0.99), and median numbers of physiotherapy visits per patient
      were three (IQR one to five) and four (two to five), respectively (p=0.001). One
      adverse reaction (an exacerbation of pain after the initial assessment) was
      recorded. INTERPRETATION: Brief pain management techniques delivered by
      appropriately trained clinicians offer an alternative to physiotherapy
      incorporating manual therapy and could provide a more efficient first-line
      approach for management of non-specific subacute low back pain in primary care.

PMID- 15950717
TI  - Gaps in policy-relevant information on burden of disease in children: a
      systematic review.
AB  - BACKGROUND: Valid information about cause-specific child mortality and morbidity
      is an essential foundation for national and international health policy. We
      undertook a systematic review to investigate the geographical dispersion of and
      time trends in publication for policy-relevant information about children's
      health and to assess associations between the availability of reliable data and
      poverty. METHODS: We identified data available on Jan 1, 2001, and published
      since 1980, for the major causes of morbidity and mortality in young children.
      Studies with relevant data were assessed against a set of inclusion criteria to
      identify those likely to provide unbiased estimates of the burden of childhood
      disease in the community. FINDINGS: Only 308 information units from more than
      17,000 papers identified were regarded as possible unbiased sources for estimates
      of childhood disease burden. The geographical distribution of these information
      units revealed a pattern of small well-researched populations surrounded by large
      areas with little available information. No reliable population-based data were
      identified from many of the world's poorest countries, which account for about a
      third of all deaths of children worldwide. The number of new studies diminished
      over the last 10 years investigated. INTERPRETATION: The number of population
      based studies yielding estimates of burden of childhood disease from less
      developed countries was low. The decreasing trend over time suggests reductions
      in research investment in this sphere. Data are especially sparse from the
      world's least developed countries with the highest child mortality. Guidelines
      are needed for the conduct of burden-of-disease studies together with an
      international research policy that gives increased emphasis to global equity and
      coverage so that knowledge can be generated from all regions of the world.

PMID- 15950718
TI  - Nasopharyngeal carcinoma.
AB  - Incidence of nasopharyngeal carcinoma has remained high in endemic regions.
      Diagnosing the disease in the early stages requires a high index of clinical
      acumen and, although most cross-sectional imaging investigations show the tumour
      with precision, confirmation is dependent on histology. Epstein-Barr virus (EBV)
      encoded RNA signal is present in all nasopharyngeal carcinoma cells, and early
      diagnosis of the disease is possible through the detection of raised antibodies
      against EBV. The quantity of EBV DNA detected in blood indicates the stage and
      prognosis of the disease. Radiotherapy with concomitant chemotherapy has
      increased survival, and improved techniques (such as intensity-modulated
      radiotherapy), early detection of recurrence, and application of appropriate
      surgical salvage procedures have contributed to improved therapeutic results.
      Screening of high-risk individuals in endemic regions together with developments
      in gene therapy and immunotherapy might further improve outcome.

PMID- 15950719
TI  - Injury-related dynamic myelin/oligodendrocyte axon-outgrowth inhibition in the
      central nervous system.
AB  - CONTEXT: By contrast with the glial scar, myelin was considered a constitutive
      static inhibitory barrier unreactive to lesions in the central nervous system
      (CNS). However, recent results suggest considerable add-on inhibition of myelin
      as a result of CNS injury. Furthermore, catastrophic events cause morphological
      and biochemical changes in the axon itself. This results in the accumulation of
      cytoskeleton components and intraaxonal transported proteins paralleled by
      extensive membrane remodelling at the axonal tip (a process called axotomy) which
      might modify the axonal response to its inhibitory environment. STARTING POINT:
      Ji-Eun Kim and colleagues recently reported an axonal subpopulation with a
      different capacity to respond to myelin inhibitors (Neuron 2004; 44: 439-51).
      Axonal specificity but also evidence for injury reactivity summarised here
      challenges our understanding of axon-growth inhibition in the injured CNS. This
      might be due to (i) qualitative and quantitative enrichment of the periaxonal
      environment by myelin/oligodendrocytes, (ii) increased axonal sensitivity to its
      inhibitory environment, and (iii) axons and lesion-induced, altered axonal
      signalling. WHERE NEXT? Postlesional reactive inhibition of myelin or the
      oligodendrocyte necessitates the development of novel screening approaches and
      therapeutic agents to promote axonal regeneration. Moreover, we need to improve
      our understanding of the pathophysiology of the lesion to find more efficient
      experimental strategies to restore neurological function.

PMID- 15950720
TI  - Addison's disease.

PMID- 15950721
TI  - A man with chest pain and glomerulonephritis.

PMID- 15950722
TI  - Ficolin A and ficolin B are expressed in distinct ontogenic patterns and cell
      types in the mouse.
AB  - Ficolins are a group of proteins characterized by the presence of collagen-like
      and fibrinogen-like domains. Two of three human ficolins, L-ficolin and H
      ficolin, are serum lectins that form complexes with mannose-binding lectin
      associated serine proteases (MASPs) and play important roles in the lectin
      complement pathway. The other human ficolin, M-ficolin, is a non-serum-type
      ficolin that is expressed in monocytes. Little is known about the physiological
      roles of ficolins. In this study, we delineated the ontogeny and cell types that
      express ficolins in mice. RT-PCR analysis showed that the expression pattern of
      ficolin A expression was closely similar to that of Masps, suggesting that these
      molecules may function in coordination as components of the lectin complement
      pathway. The cell types that express ficolin A mRNA in both adult liver and
      spleen were identified as macrophages by in situ hybridization. Ficolin B
      exhibited a distinct ontogeny pattern that switched from embryonic liver to
      postnatal bone marrow and spleen. The cells that express ficolin B mRNA were
      identified as belonging to the myeloid cell lineage by magnetic sorting and by
      subsequent RT-PCR in bone marrow cells. Thus, the different spatial-temporal
      expression patterns of ficolins A and B suggest that these molecules play
      distinct roles in the prenatal and postnatal stages.

PMID- 15950723
TI  - Identification of tribbles homolog 2 as an autoantigen in autoimmune uveitis by
      phage display.
AB  - Autoimmune uveitis is a group of ocular inflammatory disorders with unknown
      causes. As in other autoimmune diseases, identification of autoantigens from
      uveitis patients would markedly improve our understanding of the disease
      mechanism. Here, we report that a candidate autoantigen was identified by phage
      display in an unbiased fashion. A bacteriophage T7 display cDNA library was
      generated from human eye and characterized. Patient-specific phages were enriched
      by four rounds of phage display with purified patient IgG. Enriched phages
      demonstrated a 20-fold increase in binding specificity to the patient IgG
      compared with control IgG. Two clonal phages with particularly high relative
      binding specificities were isolated and characterized. The encoded genes,
      tribbles homolog 2 (TRB2) and an unknown protein, had 170- and 42-fold increases
      in their binding specificities to the patient IgG, respectively. The patient
      specific immunoreactivities were further confirmed by Western blotting. Anti-TRB2
      antibody activities were detected in several uveitis patients but not in control
      subjects, suggesting that TRB2 is a uveitis-associated candidate autoantigen.
      These results demonstrate that autoantigens can be identified by phage display
      using uveitis patient serum.

PMID- 15950724
TI  - Mapping and functional analysis of regulatory sequences in the mouse lambda5
      VpreB1 domain.
AB  - The lambda5 and VpreB genes encode the components of the surrogate light-chain
      which forms part of the pre-B cell receptor and plays a key role in B cell
      development. In the mouse, the lambda5 and VpreB1 genes are closely linked and
      are co-regulated by a multi-component locus control region. To identify the
      sequences that regulate lambda5 and VpreB1 expression during B cell development,
      we have comprehensively mapped the DNaseI hypersensitive sites (HS) in the
      lambda5-VpreB1 functional domain. The active domain contains 12 HS that are
      distributed at high density across the 18.3 kb region that forms the lambda5 and
      VpreB1 functional unit. Analysis of a reporter gene driven by the VpreB1 promoter
      in transgenic mice identified a novel enhancer associated with two HS located
      upstream of lambda5. The lambda5-VpreB1 locus was also found to be closely linked
      to the ubiquitously expressed Topoisomerase-3beta (Topo3beta) gene. The VpreB1
      and Topo3beta genes have entirely different expression patterns despite the fact
      that the two promoters are separated by a distance of only 1.5 kb.

PMID- 15950725
TI  - Identification of novel VH1/J558 immunoglobulin germline genes of C57BL/6 (Igh b)
      allotype.
AB  - Although a rich database of Igh a allotype mouse immunoglobulin germline genes
      exists, current information on Igh b allotype immunoglobulin germline genes is
      limited. Among the immunoglobulin VH genes, single-cell amplified from six Igh b
      (C57BL/6 background) spleens in this study, 602 clonally independent
      immunoglobulin VH sequences belonging to the VH1/J558 family were identified.
      Whereas 335 of these sequences could be traced to have originated from 29
      different VH1/J558 germline genes deposited in the NCBI Igblast database, the
      remaining 267 sequences appeared to have originated from 21 novel germline genes.
      Of the 50 VH1/J558 germline genes utilized in the peripheral repertoire of these
      Igh b allotype mice, the most frequently used genes included 45.21.2, V165.1,
      J558.6, J558.18A, and V23. Whereas the majority of the novel genes uncovered
      represented allelic counterparts of previously described Balb/c (Igh a allotype)
      genes, some appeared to represent truly novel germline genes. Collectively, the
      VH1/J558 germline genes exhibited high amino acid residue usage variability at
      the CDR1 positions, H31, H33, and H35, and the CDR2 positions, H50, H52, H53,
      H54, H56, and H58. The 50 VH1/J558 germline genes expressed in the peripheral Igh
      b repertoire also varied widely in the net charge of their CDR regions, raising
      the possibility that they may be differentially utilized to encode anti-nuclear
      autoantibodies.

PMID- 15950726
TI  - A novel PPAR response element in the murine iNOS promoter.
AB  - The nuclear hormone receptor peroxisome proliferation activated receptor gamma
      (PPARgamma) is a modulator of inflammation including down-regulation of inducible
      nitric oxide synthase (iNOS) and nitric oxide (NO) production. PPARgamma agonists
      reduce iNOS expression and NO production in a dose-dependent manner in
      macrophages, mesangial cells and other inflammatory cells. However, the
      mechanisms involved in the inhibition of iNOS expression by PPARgamma and its
      agonists are not fully understood. Here we show that the PPARgamma agonist
      ciglitazone dose-dependently inhibited a murine iNOS-luciferase reporter
      construct by up to 50% in transfected mesangial cells. Blocking de novo protein
      synthesis in mesangial cells had no effect on PPARgamma agonist activity,
      indicating that ciglitazone acts directly to inhibit iNOS transcription. We
      identified a novel PPAR response element (PPRE) in the murine iNOS promoter that
      is homologous to the PPRE consensus sequence. In binding assays PPARgamma
      directly binds to this response element in vitro and can function as a positive
      element in response to PPARgamma agonists when placed in front of a reporter
      gene. Site-directed mutagenesis of this PPRE in a murine iNOS promoter/reporter
      construct did not block the inhibitory activity of a synthetic PPARgamma agonist
      on the iNOS promoter/reporter construct in transfected mesangial cells. However,
      the mutated construct exhibited lower basal expression, and higher expression in
      response to inflammatory stimuli compared to the intact construct. These data
      suggest that the iNOS PPRE contributes to positive basal expression and negative
      expression of iNOS in response to inflammatory stimuli. The PPRE is not
      necessary, however, for synthetic PPARgamma agonists to inhibit iNOS expression.

PMID- 15950727
TI  - Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated
      by NK-cells in mice.
AB  - Successful treatment of stage 4 neuroblastoma remains a major challenge in
      pediatric oncology. In order to improve the outcome, passive immunotherapy using
      human-mouse chimeric monoclonal anti-disialoganglioside GD2 antibody ch14.18 has
      been evaluated in early phase clinical trials with promising results in
      progressing stage 4 neuroblastoma patients. In preparation of European phase III
      clinical trial (HR-NBL-1/ESIOP), the cell line used for production of ch14.18 was
      changed. Specifically, the plasmid encoding for ch14.18 antibody was recloned
      into CHO cells. Here, we report the in vitro and in vivo anti-neuroblastoma
      activity of antibody ch14.18 produced in CHO cells (ch14.18/CHO) compared to that
      of ch14.18 manufactured from SP2/0 (ch14.18/SP2/0) and NS0 cells (ch14.18/NS0).
      First, we demonstrate identical binding of ch14.18/CHO to the nominal antigen
      disialoganglioside GD2 in vitro compared to ch14.18/SP2/0 and ch14.18/NS0.
      Binding was GD2-specific, since all precursor- and metabolite-gangliosides of GD2
      tested were not recognized by ch14.18/CHO. Second, the functional properties of
      ch14.18/CHO were determined in complement-dependent cytotoxicity (CDC) and
      antibody-dependent cellular cytotoxicity (ADCC) reactions against GD2 positive
      neuroectodermal tumor cell lines in vitro. There was no difference in CDC
      mediated specific tumor cell lysis among the three different ch14.18 antibody
      preparations. Interestingly, ch14.18/CHO showed superior ADCC activity at low
      antibody concentrations. Third, the efficacy of ch14.18/CHO was evaluated in the
      NXS2 neuroblastoma model in vivo. Importantly, the ch14.18/CHO preparation was
      effective in suppression of experimental liver metastasis in this model. In vivo
      depletion of NK-cells completely abrogated this effect, suggesting that the
      mechanism involved in the ch14.18/CHO induced anti-neuroblastoma effect is
      mediated by NK-dependent ADCC.

PMID- 15950728
TI  - Subtle sequence differences in a tumour-associated peptide epitope translate into
      major changes in antigenicity.
AB  - Antigenicity, the ability to bind to members of repertoire of diverse immune
      receptors, is a concept that is poorly characterised with respect to its defining
      parameters. To learn more about its makeup, we have investigated the ability of
      two peptides with highly related sequences, derived from the tumour-associated
      antigen mucin-1, to recruit in vitro members from a large naive repertoire of
      synthetic human antibody fragments. One of the peptides represents the epitope
      that is immunodominant in mice. We now demonstrate that the other peptide, which
      differs from the first only by a very conservative aspartate-threonine to
      glutamate-serine change, is much less antigenic than the first peptide. This is
      so despite the fact that there is no observable difference in the tendency of the
      two peptides to adopt a structure in solution. Furthermore, the peptides differ
      in their immunodominant parts and the less antigenic peptide selects for antibody
      fragments targeting residues outside of the epitope considered to be
      immunodominant in mice. We conclude that subtle sequence changes greatly, affect
      antigenicity and immunodominance of epitopes in this important tumour-associated
      antigen.

PMID- 15950729
TI  - Biochemical and structural impact of natural polymorphism in the HLA-A3
      superfamily.
AB  - Class I alleles of the HLA-A3 superfamily (-A*0301, -A*1101, -A*3101, -A*3301,
      and -Aw*6801) share largely overlapping peptide repertoires. Cross-reactive T
      cell responses between HLA-A3-like molecule/peptide complexes have been
      demonstrated in vitro and during natural diseases. In spite of this immune
      relatedness, HLA-A3-like molecules exhibit noticeable differences in their
      antigen-selecting and -presenting properties. Identifying molecular and
      structural features responsible for these differences is important for
      understanding how natural polymorphism leads to functional divergence within the
      HLA-A3 superfamily. Towards this goal, we used an approach that combines thermal
      stability data on recombinant, soluble HLA-A3-like molecules complexed with a
      nonamer and decamer HIV-1 peptide, together with a detailed structural analysis
      of these HLA-A3-like molecule/peptide complexes based on crystal and molecular
      model structures. Our studies revealed the importance of residues 9 and 67 for
      modulating peptide selection within the B pocket; of residue 97 for modulating
      peptide selection within the F pocket interdependently with the presence (or
      absence) of a middle, secondary anchor residue; and of residues 70, 73, 97, 152,
      and 156 for modulating peptide presentation in the central region of the groove
      that leads to altered antigenic surfaces. Overall, our detailed assessment of the
      biochemical and structural impact of natural polymorphism within the HLA-A3
      superfamily has permitted to understand how HLA-A3-like molecules differ at the
      level of their primary and secondary anchor pockets causing fine differences in
      their peptide-selecting and -presenting properties. A better understanding of the
      molecular immunological properties of HLA-A3-like molecules is significantly
      important for the rationale design of broad peptide-based vaccines.

PMID- 15950730
TI  - Selective up-regulation of caspase-3 gene expression following TCR engagement.
AB  - Activation-induced cell death (AICD) in T lymphocytes depends on the expression
      of Fas-ligand, which triggers the apoptotic process after binding to its receptor
      Fas. This leads to the activation of cysteine proteases of the caspase family and
      especially of caspase-3, a critical effector protein during AICD. We have
      previously observed the up-regulation of caspase-3 expression in effector but not
      memory T cells stimulated in vivo. In this study, we further characterized the
      regulation of caspase expression following T cell receptor (TCR) signaling and
      demonstrate that a three-fold increase in caspase-3 mRNA levels was observed by
      semi-quantitative and real-time RT-PCR analysis. Caspase-3 expression was
      selectively increased among five different caspases following TCR stimulation, as
      assessed by RNase protection assay. Real-time RT-PCR analysis demonstrated that a
      three-fold up-regulation in caspase-3 mRNA levels was observed following TCR
      triggering, whereas caspase-8 mRNA levels remained unchanged. The increase in
      caspase-3 mRNA levels occurred before cleavage and activation of caspase-3 and in
      the absence of apoptosis. TCR-mediated induction in caspase-3 expression was not
      dependent on STAT1 activation, since following stimulation of KOX-14 cells the
      transcription factor was not phosphorylated. Together, these results show that
      TCR activation triggers the selective increase in caspase-3 mRNA levels,
      independently of caspase activity and the induction of apoptosis.

PMID- 15950731
TI  - Constitutive expression of three novel catfish CXC chemokines: homeostatic
      chemokines in teleost fish.
AB  - Chemokines are best known for their vital role in leukocyte chemotaxis, as part
      of the larger inflammatory response. Expression analysis and functional
      characterization of chemokines in mammalian species have often overlooked the
      role of these proteins under homeostatic conditions. Recent investigations of
      chemokine diversity in teleost fish have also centered on the immune-related
      functions of chemotactic cytokines, such as CXCL8 and CXCL10. While a disease
      based approach to chemokines is essential to the development of remediative
      therapies for both human and animal infections, it may be a poor measure of the
      overall complexity of chemokine functions. As part of a larger effort to assess
      the conservation of chemokine diversity in teleost fish, we report here the
      identification of three novel, constitutively expressed CXC chemokines from
      channel catfish (Ictalurus punctatus). Phylogenetic analyses indicated that two
      of the three CXC chemokines were orthologues for mammalian CXCL12 and CXCL14,
      respectively. Whereas a clear orthology could not yet be established for the
      third CXC chemokine, it shared highest amino acid identity with mammalian CXCL2.
      All three CXC chemokines show expression in a wide range of tissues, and early
      expression during development was observed for CXCL12. The expression of this new
      set of catfish CXC chemokines was not induced during challenge by infection of
      Edwardsiella ictaluri, the causative agent of the fish pathogen enteric
      septicemia of catfish. In contrast to the gene duplication of CXCL12 in carp and
      zebrafish, Southern blot analysis indicated that all three catfish CXC chemokines
      exist as single copy genes in the catfish genome suggesting that gene duplication
      of CXC chemokines in specific teleost fish was a recent evolutionary event.

PMID- 15950732
TI  - Cys74 and Cys163 are necessary for IL-18 to elicit IFN-gamma production from
      peripheral blood lymphoid mononuclear cells.
AB  - There are four cysteines (Cys74, Cys104, Cys112 and Cys163) in mature human IL-18
      (hIL-18). These cysteines are highly conserved in IL-18s of 11 species cloned so
      far, suggesting that one or more of the cysteines may be important for hIL-18
      function. In this study, each cysteine residue was individually replaced with
      serine by site-directed mutagenesis. The wild type and mutant IL-18s were
      expressed in Escherichia coli and renatured by two renaturing methods. The
      purified wild type and mutant rhIL-18s were assayed for their capacity of
      inducing IFN-gamma and activating NF-kappaB from ConA-stimulated PBMC. DNA
      binding activity of NF-kappaB was performed by electrophoretic mobility-shift
      analysis. Our results showed that the mutant rhIL-18C74S and C163S induced much
      less amount of IFN-gamma from PBMC and the decrement of NF-kappaB DNA binding
      activity was also observed from C74S and C163S treated PBMC. These results
      indicate that functional hIL-18 has an absolute requirement for residues Cys74
      and Cys163.

PMID- 15950733
TI  - Jalpha-gene segment usage and the CDR3 diversity of porcine TCRalpha-chain cDNA
      clones from the PBL of a five-month-old pig and the thymus of a one-month-old
      pig.
AB  - Porcine T-cell receptor alpha (TCRalpha)-chain cDNA clones were isolated from
      libraries made from two different sources, the thymus of a 1-month-old LW strain
      pig and the peripheral blood lymphocytes (PBL) of a 5-month-old Clawn strain pig.
      Among 109 cDNA clones with the Jalpha-gene segment, 44 different Jalpha-gene
      segments were found out of the 61 Jalpha-gene segments previously identified in
      the porcine germline sequence. Among the 103 complete TCRalpha-chain cDNA clones
      with the rearranged Valpha- and Jalpha-gene segments, 33 different Valpha-gene
      segments were identified, which randomly rearranged to Jalpha-gene segments
      indicating lack of any specific combinations between Valpha- and Jalpha-gene
      segments with only one exception of the same set of Jalpha-gene segments in
      duplicate clones. Among the cDNA clones from PBL of an individual 5-month-old
      Clawn strain pig, a broad distribution of the Jalpha-gene segment usage was
      observed over the entire Jalpha-gene cluster. The Jalpha-gene segment usage in an
      individual 1-month-old thymus from a LW strain pig also gave a pattern consistent
      with the 5-month-old pig. These distributions of the Jalpha-gene segment usage
      were similar to the previously reported patterns for human T-cells and those of
      adult murine T-cells. Among the porcine cDNA clones isolated, TCRalpha-chain CDR3
      length ranged from 4 to 14 amino acids with the average being 9.35 amino acids.
      Present report provides groundwork for further studies on porcine TCRalpha-chain
      expression.

PMID- 15950734
TI  - Phosphorylation of p42/44 MAP kinase is required for rF1-induced activation of
      murine peritoneal macrophages.
AB  - The Fraction 1 (F1) antigen of Yersinia pestis is known to induce thymocyte
      proliferation. It serves as a major protective antigen against challenge of Y.
      pestis. Recently, we reported rF1-induced activation of macrophages. Current
      investigation elucidates the role of p42/44 mitogen-activated protein kinases
      (MAPK)-mediated signal transduction in murine peritoneal macrophages on
      stimulation with rF1 (10 microg/ml) in vitro. The p42/44 MAPK activation was
      determined by studying the expression of the phosphorylated p42/44 MAPK in rF1
      treated macrophages. PD98059, a specific inhibitor of MAPK kinase (MEK) inhibited
      the p42/44 MAPK phosphorylation, indicating the specificity of the above
      response. Furthermore, the rF1-induced phosphorylation of p42/44 MAPK is found to
      blocked by upstream protein kinase C inhibitor H7, tyrosine kinase inhibitor
      genistein and phosphoinositol-3-kinase (PI3-K) inhibitor wortmannin.
      Additionally, phosphorylation of JNK and activation of the transcription factor,
      c-jun and c-fos was also observed in response to rF1 treatment. The rF1-induced
      activation of p42/44 MAPK was correlated to the functional activation of
      macrophages by demonstrating the inhibition of actin rearrangement, IL-1, TNF
      alpha and NO production caused by PD98059 in the rF1-treated macrophages.

PMID- 15950735
TI  - IgG naturally occurring antibodies stabilize and promote the generation of the
      alternative complement pathway C3 convertase.
AB  - Normal human IgG contains naturally occurring anti-C3 antibodies (anti-C3 NAbs)
      that have been proposed to regulate complement amplification. Here, we report a
      novel procedure for anti-C3 NAb purification. Pooled human IgG was fractionated
      on a DEAE column prior to affinity chromatography on IgG and then on C3. Anti-C3
      NAbs co-purified with anti-F(ab')2 NAbs. In a refined protocol, IgG fractions
      were absorbed on Fc, F(ab')2, and C3, which allowed to isolate the directly
      accessible NAbs and to remove IgG hinge-region-specific NAbs. Since a substantial
      fraction of total anti-C3 NAbs in whole IgG pre-existed as complexes, IgG that
      did not bind to the three affinity columns was treated with urea and the affinity
      chromatography repeated to collect the dissociated NAbs. The urea-accessible anti
      F(ab')2 NAbs were rather pure but anti-C3 NAbs yet contained substantial amounts
      of anti-F(ab')2 NAbs. Anti-C3 NAbs showed up to 400-fold and anti-F(ab')2 NAbs,
      up to 30-fold enrichment as compared to pooled normal human IgG. Anti-C3 NAb
      preparations exhibited nephritic factor activity that was up to 60 times stronger
      than that of total IgG from a patient with membranoproliferative
      glomerulonephritis type 2. In addition, anti-C3 NAbs promoted C3 convertase
      generation, when added to the convertase precursor or during convertase assembly,
      suggesting a non-nephritic-factor mechanism. Factors H and I reduced the overall
      level of activity but had no influence on the NAb dose-response curve meaning
      that NAbs did not interfere with factor H binding. Convertase promoting activity
      during assembly correlated with the content of anti-C3 NAbs in NAb complexes. In
      conclusion, anti-C3 NAbs associated with framework-specific anti-idiotypic NAbs
      stabilize C3 convertase and promote its generation but their activity is
      compensated for in whole IgG.

PMID- 15950736
TI  - Transcriptional regulation of the murine C5a receptor gene: NF-Y is required for
      basal and LPS induced expression in macrophages and endothelial cells.
AB  - The anaphylatoxin receptors of the complement system are important in immune
      defense but also play a role in autoimmune disease. Reports have demonstrated
      induced C5a receptor (C5aR) expression in a number of disease states, yet little
      is known about the regulation of this gene. We have examined sequences in the
      presumptive promoter-enhancer region in order to study the regulation of this
      gene. Rapid amplification of cDNA ends (RACE) analyses were used to identify the
      transcriptional start site, and we then cloned 2278 bp of sequence from this
      region for use in luciferase assays. Deletion analyses of 5' sequences
      demonstrated that the majority of this region is dispensable for expression in
      macrophages and endothelial cells (ECs). A 232 bp region proximal to the
      transcription start site was fully capable of directing expression in macrophages
      and ECs, while being minimally active in cells that do not express the receptor.
      The transcriptional regulatory site most critical for this expression matches the
      consensus sequence for nuclear factor-Y (NF-Y) at position -96. Site-directed
      mutagenesis of this site resulted in a 70-90% decrease in luciferase activity
      depending on the cell type. Electrophoretic mobility shift/supershift assay
      (EMSA) analyses demonstrated the specific binding of NF-Y to labeled
      oligonucleotides containing the putative CCAAT site with macrophages and EC
      nuclear extracts, and antibodies to NF-Y were able to supershift this -96 NF-Y
      complex. We also demonstrate LPS leads to enhanced C5aR transcription and this is
      mediated predominantly through the NF-Y site. The data reported in this study
      might be critical for determination of transcription factors that can be targeted
      pharmacologically to modulate the expression of the C5aR in infectious disease or
      autoimmunity.

PMID- 15950737
TI  - The Tritope Model for restrictive recognition of antigen by T-cells I. What
      assumptions about structure are needed to explain function?
AB  - Given that the recognition of the allele-specific determinants expressed by MHC
      encoded restricting elements (R) is germline encoded and selected, whereas the
      recognition of peptide (P) is somatically encoded and selected, then two
      different combining sites must be under selection. This necessitates a
      multirecognitive-single T-cell antigen-receptor (TCR) with anti-R and anti-P
      paratopes that function in concert to signal restrictive reactivity. The
      consequences of this "two repertoire" postulate not only gives us a concept of
      TCR structure quite distinct from that at present generally accepted, but, in
      addition, resolves many existent contradictions. The problems of the positive and
      negative selection, alloreactivity, Self-Nonself (S-NS) discrimination, the
      nature and size of the repertoire, and the related experimental interpretations,
      are discussed. Further the Tritope Model is compared with previously proposed
      models to justify why a competing model is warranted.

PMID- 15950738
TI  - Humanization of an anti-human TNF-alpha antibody by variable region resurfacing
      with the aid of molecular modeling.
AB  - The murine monoclonal antibody Z12 is of therapeutic interest for its
      neutralizing biological activity against human tumor necrosis factor-alpha (hTNF
      alpha). We attempted to humanize Z12 with variable domain resurfacing guided by
      computer modeling. First, the genes of heavy and light chain variable region (VH,
      VL) of Z12 were cloned and the whole three-dimensional structure of Fv fragment
      was constructed by using homology-based modeling and molecular docking methods.
      Then the complex model of Fv interacting with hTNF-alpha whose crystal structure
      derived from PDB database was gained with computer-guided docking program. Based
      on this model, a humanized version was designed. The humanized Fab antibody was
      constructed, expressed and purified in the pComb3H vector system and it showed
      unaltered binding affinity to the antigen as determined by ELISA and atomic force
      microscopy (AFM). The method described here can be used to humanize other anti
      hTNF-alpha antibodies.

PMID- 15950739
TI  - Bcl6 regulates Th2 type cytokine productions by mast cells activated by
      FcepsilonRI/IgE cross-linking.
AB  - Bcl6-deficient (Bcl6-/-) mice displayed Th2 type inflammation, which caused by
      abnormality of non-lymphoid cells. However, initiators for the Th2 type
      inflammation were not clear. In order to elucidate the initiators, we
      investigated property and function of mast cells derived from Bcl6-/- mice. Mast
      cells were developed from bone marrow cells cultured with IL-3 (BMMCs). Although
      the development of BMMCs from Bcl6-/- mice was similar to that from wild-type
      mice, proliferation of Bcl6-/- BMMCs stimulated with IL-3 was slightly lower than
      that of wild-type BMMCs. When these BMMCs were stimulated by FcepsilonRI/IgE
      cross-linking, Bcl6-/- BMMCs produced Th2 cytokines more than wild-type BMMCs
      did. Thus, Bcl6-/- mast cells are one of the initiators for Th2 type inflammation
      in Bcl6-/- mice, and Bcl6 may be a molecular target for Th2 type allergic
      diseases.

PMID- 15950740
TI  - Repertoire diversification in mice with an IgH-locus-targeted transgene for the
      rearranged VH domain of a physiologically selected anti-ssDNA antibody.
AB  - To test the fate of developing B cells with autoreactive receptor components, we
      studied mice homozygous for a knock-in transgene coding the VH domain of an IgM
      ssDNA-binding antibody. The transgene has unmutated C57 BL/6 V gene segments.
      Homozygous knock-in mice developed normal numbers of spleen and bone marrow B
      cells and normal serum Ig concentrations, and had the same low level of serum
      anti-ssDNA antibody as non-transgenic mice. Mature B cells expressed the
      transgene, and it underwent mutation and class switching. In young knock-in
      animals, nearly all IgM and some IgG cDNA clones from bone marrow and spleen
      contained the transgene V(H)D(H)J(H), with few or no mutations. In many IgM
      clones from older animals, however, and many IgG clones from both young and old
      mice, VH domains were revised by productive replacement with a new V(H)D(H)
      segment. VL segments were diverse. Immunized homozygous knock-in mice produced
      serum antibodies to polysaccharide, nucleic acid and protein antigens. Monoclonal
      IgM and IgG antibodies to nucleic acids used either transgenic or revised VH
      domains; but all of 20 IgG monoclonal antibodies to thyroglobulin used revised VH
      domain genes. Thus, B cells expressing an autoreactive (ssDNA-binding) VH domain
      did progress through development and were precursors for cells producing IgM and
      IgG, but underwent extensive VH gene revision in diversification of antibody
      responses.

PMID- 15950741
TI  - Porcine TCR CD3zeta-chain and eta-chain.
AB  - Complete porcine CD3zeta-chain cDNA sequence was obtained for the first time, and
      its genomic nucleotide sequence was investigated from exon 2 down to CD3eta-chain
      exon 8. The sequence of porcine CD3zeta-chain showed homologous amino acid
      sequence with human and murine counterparts, in contrast to CD3eta-chain exon 8
      with diversity among animals previously investigated. CD3eta-chain peptide is an
      alternative splice form of CD3zeta-chain exon 7 splicing to CD3eta-chain exon 8
      instead of CD3zeta-chain exon 8. The genomic sequences revealed that the splice
      acceptor sequences of CD3eta-chain exon 8 of all animals investigated to be
      completely uniform. Further, CD3eta-chain exon 8 amino acid sequences retained
      the unique characters of having high proline (Pro) and positively charged amino
      acid content except for rats and mice. Although the biological role of CD3eta
      chain remains to be enigmatic, these evidences suggests the evolutional pressure
      to maintain its sequence.

PMID- 15950742
TI  - Adjuvant effect of Taenia crassiceps glycans against leishmanial antigens in mice
      infected with Leishmania mexicana.
AB  - Complex glycans derived from lipid, nucleic acid and protein free extracts of
      Taenia crassiceps metacestode larvae were found to have adjuvant effect against
      Leishmania mexicana antigens in BALB/c mice experimentally infected with L.
      mexicana. A single intraperitoneal or subcutaneous injection of Taenia glycans
      altered the Th-1/Th-2 balance in experimentally infected mice as determined by
      Western blot analysis of IgG 1 and IgG 2a antibodies to L. mexicana antigens.
      Leishmania antigens which were immunogenic in Taenia glycan vaccinated mice were
      different from those of non-vaccinated mice. Vaccination induced leishmania
      antigen specific IFN-gamma expression in vitro culture by spleen cells from
      Taenia glycan vaccinated-leishmania infected mice and not from mock vaccinated
      leishmania infected BALB/c mice. We conclude that T. crassiceps glycans have
      immunoadjuvant effects against leishmania and may be developed as adjuvants in
      anti-leishmania vaccines.

PMID- 15950743
TI  - Cloning and characterisation of the primary structure of the sheep lymphocyte
      function-associated antigen-1 alpha subunit.
AB  - The leukocyte integrins play a critical role in a number of cellular adhesive
      interactions during the immune response. The ovine cDNA encoding CD11a, the
      predominant alpha subunit of the beta2-integrin family, was sequenced and
      compared with the human, bovine and murine sequences. Despite some focal
      differences, it shares all the main characteristics of its known mammalian
      homologues. Along with the ovine CD18-encoding cDNA, which is available for a few
      months, the sequence data provided here will allow the Ovis aries beta2-integrin
      CD11a/CD18 (LFA-1, alpha(L)beta2) expression in vitro as a tool to examine the
      specificities of inflammation in the ovine species.

PMID- 15950744
TI  - Submolecular recognition profiles in two mouse strains of non-protective and
      protective antibodies against botulinum neurotoxin A.
AB  - We have used a set of synthetic overlapping peptides encompassing the entire
      heavy (H) chain of botulinum neurotoxin serotype A (BoNT/A) to map, in two mouse
      strains (BALB/c, H2d, and SJL, H2S), the regions on the H-chain recognized by Abs
      in the last bleed of non-protective anti-BoNT/A antisera and in the bleed of
      protective antisera immediately following it in the bleeding schedule. Although
      the protective antisera bound slightly higher amounts of total (IgG+IgM) Abs, non
      protective and protective BALB/c antisera showed similar peptide-binding profiles
      involving peptides N6/N7, N25, C2/C3, C9/C10/C11, C15, C18, C24, C30, and C31
      and, at lower amounts of bound Abs, peptides N19, C6/C7, and C28. IgG+IgM
      antibodies of the protective SJL antisera recognized peptides N5, N22, and C21,
      and these peptides were only slightly recognized (N22, C21) or unrecognized (N5)
      by the non-protective antisera. Additionally, peptides N7/N8, N25, C11, C15, and
      less so N27/N28 bound two-fold or more Abs from the SJL protective antisera than
      the non-protective antisera. The Abs bound to peptides C4 and C29 were of
      relatively lower affinity. Peptides C2/C3, C7, C18/C19, C24, C30, and C31 bound
      higher amounts of Abs in the SJL protective versus the non-protective antisera,
      but the differences were less than double. We also mapped the binding profiles of
      the IgG Abs in these sera. BALB/c and SJL had 13-36-fold higher of IgG Abs that
      bound to BoNT/A in the protective antisera relative to non-protective antisera.
      The IgG Abs in the protective antisera of each mouse haplotype bound to the same
      peptides that bound total Abs in the correlate antiserum. But in both mouse
      strains, the non-protective Abs showed little or no IgG Abs that bound to these
      peptides. In the SJL haplotype, the IgG response to peptide N5 was transient,
      appearing strongly in early protective Abs and disappearing by day 70. It is not
      clear whether the response to region N5 plays a role in initiating and
      contributing to the protective activity of the toxin in the SJL strain in the
      early stages but is not needed in later hyperimmune stages of the Ab response. It
      is concluded that the switch in BALB/c and SJL mice from non-protective to
      protective Abs is not associated with major changes in the epitope-recognition
      profiles. Although some slight differences between non-protective and protective
      antisera appeared in their levels of Abs that were bound by some peptides, these
      differences are not sufficient to explain differences in the protection
      properties. Protection was mostly associated with the immunoglobulin class of the
      antibodies. IgM antibodies were non-protective, while IgG Abs produced after the
      switch were protective.

PMID- 15950745
TI  - The inhibitory leukocyte-associated Ig-like receptor-1 (LAIR-1) is expressed at
      high levels by human naive T cells and inhibits TCR mediated activation.
AB  - Human leukocyte-associated Ig-like receptor-1 (LAIR-1) is a transmembrane
      glycoprotein with a single extracellular Ig-like domain and a cytoplasmic tail
      containing two immunoreceptor tyrosine-based inhibition motifs (ITIMs). It is
      constitutively expressed on the majority of human mononuclear leukocytes and
      functions as an inhibitory receptor. In this study, we show that freshly isolated
      peripheral blood T cells are heterogeneous in their expression levels of LAIR-1.
      We have found that naive T cells express the highest levels of LAIR-1, even more
      than memory cells. The cross-linking of LAIR-1 inhibits T cell receptor (TCR)
      mediated signals in freshly isolated human naive T cells and whole populations of
      CD4+ or CD8+ T cells. TCR cross-linking increased cell surface expression of LAIR
      1 in a process that requires p38 MAP kinase and ERK signaling. Altogether, these
      results indicate that LAIR-1 is capable of negatively regulating T cell
      functions, and its high level of expression by naive T cells suggests that it may
      function at an early stage in the development of an immune response.

PMID- 15950746
TI  - Immunosuppressive agents mediate reduced allostimulatory properties of myeloid
      derived dendritic cells despite induction of divergent molecular phenotypes.
AB  - Immunosuppressive drugs such as glucocorticoids (dexamethasone (Dexa)),
      cyclosporin A (CsA) and tacrolimus (Tacro) have been shown to impair
      differentiation and/or function of immunostimulatory dendritic cells (DC(ims)).
      Phenotypes and functions of the resultant myeloid dendritic cells, however, have
      not yet been thoroughly elucidated. We show here that all DC subsets generated by
      treatment with immunosuppressive agents exhibited considerably reduced
      allostimulatory properties as measured in the primary mixed lymphocyte reaction
      (tacrolimus>cyclosporin A>dexamethasone, used at equimolar concentrations). In
      the MLR, all these DC subsets furthermore inhibited secretion of the T-helper
      type 1 cytokine IFN-gamma; in addition, DC-Tacro and, less so, DC-CsA induced the
      T-helper type 2 cytokine IL-4. Upon FACS analysis, DC-Tacro and DC-CsA exhibited
      phenotypic features similar to DC(ims). In addition, DC-CsA and, to a smaller
      extent, DC-Tacro were characterized by increased mRNA expression of the novel
      costimulatory molecule B7-H2 (ICOS-ligand). In contrast, dexamethasone induced
      the generation of DC characterized by decreased expression of CD83 and CD86, by
      de novo expression of plasmacytoid and myeloid cell markers CD123 and CD14,
      respectively, and by sustained expression of Toll-like receptor 2. Interestingly,
      activation of DC-Dexa with a specific TLR2 ligand induced a strong up-regulation
      of IL-10 along with TNF-alpha and IL-6, a combination of cytokines that allow
      amplification of regulatory DC populations. In conclusion, myeloid DC induced by
      dexamethasone as well as by CsA or tacrolimus show reduced allostimulatory
      properties; however, they are equipped with different molecular repertoires to
      exert these functions.

PMID- 15950747
TI  - FcepsilonRI cross-linking activates a type II phosphatidylinositol 4-kinase in
      RBL 2H3 cells.
AB  - Crosslinking of FcepsilonRI on rat basophilic leukemia (RBL 2H3) cells leads to
      an increase in Phosphatidylinositol 4-kinase activity. This increase in Ptdlns 4
      kinase activity is strongly correlated with its tyrosyl phosphorylation state.
      Characterization of the enzyme activity in anti phosphotyrosine
      immunoprecipitates suggests it as a type II Ptdlns 4-kinase. Membrane cholesterol
      depletion studies showed a reduction in type II Ptdlns 4-kinase activity
      suggesting that lipid rafts play an important role in activation of the enzyme.
      The enzyme activity was inhibited by resveratrol. In situ inhibition of type II
      Ptdlns 4-kinase activity showed a reduction in beta-hexosaminidase release upon
      FcepsilonRI cross-linking. These studies suggest that a type II Ptdlns 4-kinase
      is an integral component of FcepsilonRI mediated signal transduction mechanisms.

PMID- 15950748
TI  - Mechanism of action of a novel viral mutagenic covert nucleotide: molecular
      interactions with HIV-1 reverse transcriptase and host cell DNA polymerases.
AB  - A novel non-chain terminating nucleoside analog anti-HIV inhibitor, KP-1212 has
      been designed to form base pairs with multiple bases that may lead to mutagenesis
      in the HIV-1 viral genome. After multiple replication cycles, the accumulation of
      mutations surpasses a crucial threshold beyond which the virus can no longer
      replicate. HIV-1 reverse transcriptase (RT) incorporates the KP-1212
      monophosphate into the genome during viral replication after metabolic activation
      of the KP-1212 nucleoside to the triphosphate. The propensity for forming
      alternate base pairs with the KP-1212 nucleotide leads to mismatched nucleotides
      and the subsequent misincorporation is the basis for the inhibitory activity. The
      results showed that HIV-1 RT and human mitochondrial DNA polymerase (Pol gamma)
      incorporated KP-1212-TP with a significant level of efficiency, whereas mouse DNA
      polymerase beta (Pol beta) did not. Misincorporation studies suggest that both
      HIV-1 RT and Pol gamma may cause mutations at significantly high rates. These in
      vitro data confirm the mechanistic basis of KP-1212 as a viral mutagen but
      suggest that there may be a potential for toxicity to the mitochondria.

PMID- 15950749
TI  - Live cell imaging reveals distinct roles in cell cycle regulation for Nek2A and
      Nek2B.
AB  - Two splice variants of Nek2 kinase, a member of the NIMA-related family, have
      been identified as Nek2A and Nek2B. Nek2A regulates centrosome disjunction,
      spindle formation checkpoint signaling, and faithful chromosome segregation. A
      specific role for Nek2B has not yet been identified. Here, we have examined the
      distinct roles of Nek2A and Nek2B using timelapse video microscopy to follow the
      fate of cells progressing through the cell cycle in the absence of either Nek2A
      or Nek2B. We show that the down-regulation of Nek2B leads to a mitotic delay in
      the majority of cells. Upon exiting mitosis, cells exhibit mitotic defects such
      as the formation of multinucleated cells. Such phenotypes are not observed in
      cells that exit mitosis in the absence of Nek2A. These observations suggest that
      Nek2B may be required for the execution of mitotic exit.

PMID- 15950750
TI  - Early signaling interactions between the insulin and leptin pathways in bovine
      myogenic cells.
AB  - Cross-talk between hormone signaling pathways provides mechanisms to facilitate
      flexibility in the cellular response to extracellular conditions. One function of
      insulin is to signal high extracellular glucose, while leptin may signal the
      abundance of extracellular lipid, both energy sources being readily utilized by
      muscle. The present study reports early signaling events in the insulin and
      leptin cascades in primary bovine myogenic cells (BMC). BMC were treated with
      insulin, or leptin for 1, 10, 30 and 120 min, or pretreated with leptin for 10
      min followed by insulin for 1, 10, 30 and 120 min. BMC were insulin resistant,
      showing a significant inhibition of IRS-1 association with the insulin receptor
      (IR) following insulin stimulation, a corresponding increase in PI 3-kinase
      association with the IR, and a slow and modest increase in GLUT4 recruitment to
      the plasma membrane. Pretreatment of BMC for 10 min leptin, followed by insulin
      time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid,
      phasic response of PI 3-kinase recruitment to the IR and abrogated the response
      of GLUT4 translocation to the plasma membrane evoked by insulin alone. The lack
      of insulin response was independent of IR abundance or affinity. JAK-2
      association with the ObR and JAK-2 tyrosine phosphorylation were responsive to
      all three treatments. Insulin alone down-regulated the leptin signaling pathway,
      JAK-2 association with ObR decreased at all time-points, and JAK-2
      phosphorylation decreased similarly. Leptin alone also appeared to down-regulate
      JAK-2 association with the ObR, but stimulated the down-regulated pathway to
      signal, JAK-2 tyrosine phosphorylation being increased at later time-points.
      Pretreatment with leptin followed by insulin time-course showed marked up
      regulation of the early leptin signaling pathway, JAK-2 association with the ObR
      being increased by insulin while JAK-2 tyrosine phosphorylation was also
      increased. The contrasting responses of BMC to insulin alone, leptin alone and
      the sequential leptin-insulin treatment may point to the ability of these cells
      to respond to energy substrate availability, as bovine muscle has evolved to
      utilize lipids and fatty acids in response to a metabolism which provides only
      limited glucose. This cross-talk between insulin and leptin signaling pathways
      points to a better understanding of the mechanisms driving energy substrate
      utilization in ruminant muscle and may provide a useful model for greater
      understanding of the molecular mechanisms underlying the development of insulin
      resistance and Type 2 diabetes in man.

PMID- 15950751
TI  - Detection of receptor trimers on the cell surface by flow cytometric fluorescence
      energy homotransfer measurements.
AB  - Fluorescence energy homotransfer offers a powerful tool for the investigation of
      the state of oligomerization of cell surface receptors on a cell-by-cell basis by
      measuring the polarized components of fluorescence intensity of cells labeled
      with fluorescently stained antibodies. Here we describe homotransfer-based
      methods for the flow cytometric detection and analysis of hetero- and homo
      associations of cell surface receptors. Homotransfer efficiencies for two- and
      three-body energy transfer interactions are defined and their frequency
      distribution curves are computed from the fluorescence anisotropy distributions
      of multiple-labeled cells. The fractions of receptors involved in homo-clustering
      is calculated based on the dependence of the fluorescence anisotropy on the
      surface concentration of the fluorescently stained antibodies. A homotransfer
      analysis of the homo- and hetero-clustering of the MHCI and MHCII glycoproteins,
      the cytokine receptor IL-2Ralpha, transferrin receptor and the receptor-type
      tyrosine phosphatase CD45 on JY B and Kit-225-K6 T cells is presented. We
      investigated how various factors such as the type of dye, rotational mobility of
      the dye and dye-targeting antibody, as well as the wavelength of the exciting
      light affect the homotransfer. We show that the homotransfer technique combined
      with the high statistical resolution of flow cytometry is an effective tool for
      detecting different oligomeric states of receptors by using fluorophores having
      restricted rotational mobility on the time scale of fluorescence.

PMID- 15950752
TI  - NADPH oxidase homologs are required for normal cell differentiation and
      morphogenesis in Dictyostelium discoideum.
AB  - Membrane-associated NADPH oxidase complexes catalyse the production of the
      superoxide anion radical from oxygen and NADPH. In mammalian systems, NADPH
      oxidases form a family of at least seven isoforms that participate in host
      defence and signalling pathways. We report here the cloning and the
      characterisation of slime mould Dictyostelium discoideum homologs of the
      mammalian heme-containing subunit of flavocytochrome b (gp91(phox)) (NoxA, NoxB
      and NoxC), of the small subunit of flavocytochrome b (p22(phox)) and of the
      cytosolic factor p67(phox). Null-mutants of either noxA, noxB, noxC or p22(phox)
      show aberrant starvation-induced development and are unable to produce spores.
      The overexpression of NoxA(myc2) in noxA null strain restores spore formation.
      Remarkably, the gene alg-2B, coding for one of the two penta EF-hand proteins in
      Dictyostelium, acts as a suppressor in noxA, noxB, and p22(phox) null-mutant
      strains. Knockout of alg-2B allows noxA, noxB or p22(phox) null-mutants to return
      to normal development. However, the knockout of gene encoding NoxC, which
      contains two penta EF-hands, is not rescued by the invalidation of alg-2B. These
      data are consistent with a hypothesis connecting superoxide and calcium
      signalling during Dictyostelium development.

PMID- 15950753
TI  - Functional properties of a recombinant bacterial DING protein: comparison with a
      homologous human protein.
AB  - DING proteins are highly-conserved proteins with poorly-defined cell-signalling
      roles in mammals. Conserved homologues are also commonplace in plants, though not
      as yet functionally characterized. Poor availability of the proteins, and a lack
      of genetic structure, hamper progress in elucidating the roles of these
      eukaryotic DING proteins, but highly-homologous hypothetical DING proteins have
      recently been identified in Pseudomonas genomes. We have cloned and expressed a
      DING protein from P. fluorescens SWB25 in Escherichia coli. The recombinant
      protein, and its natural human homologue, act as phosphate-binding proteins, as
      predicted by structural homologies with other bacterial proteins. The recombinant
      protein also displays other functional similarities with mammalian DING proteins,
      in that, like the human version, it acts as a mitogen for cultured human cells,
      and can bind cotinine, known to be a binding ligand for a rat neuronal DING
      protein.

PMID- 15950754
TI  - Paclitaxel resistance in cells with reduced beta-tubulin.
AB  - We previously described the isolation of colcemid resistant Chinese hamster ovary
      cell lines containing alpha- and beta-tubulin mutations that increase microtubule
      assembly and stability. By analyzing colcemid sensitive revertants from one of
      the beta-tubulin mutants, we now find that loss or inactivation of the mutant
      allele represents the most common mechanism of reversion. Consistent with this
      loss, the revertants have 35% less tubulin at steady state, no evidence for the
      presence of a mutant polypeptide, and a normal extent of tubulin polymerization.
      In addition to the loss of colcemid resistance, the revertant cells exhibit
      increased resistance to paclitaxel relative to wild-type cells. This paclitaxel
      resistance can be suppressed by transfecting the revertant cells with a cDNA for
      wild-type beta-tubulin, indicating that the reduction in tubulin in the revertant
      cells is responsible for the resistance phenotype. We propose that reducing
      tubulin levels may represent a novel mechanism of paclitaxel resistance.

PMID- 15950756
TI  - Modulatory effect of glutathione status and antioxidants on methylmercury-induced
      free radical formation in primary cultures of cerebral astrocytes.
AB  - Excessive free radical formation has been implicated as one of the causative
      factors in neurotoxic damage associated with variety of metals, including
      methylmercury (MeHg). Although the mechanism(s) associated with MeHg-dependent
      neurotoxicity remains far from clear, overwhelming data give credence to a
      mediatory role for astrocytes, a major cell type that preferentially accumulates
      MeHg. To extend our recent findings of MeHg-induced increase in ROS formation (G.
      Shanker, J.L. Aschner, T. Syversen et al., Free radical formation in cerebral
      cortical astrocytes in culture induced by methylmercury, Mol. Brain Res. 128
      (2004) 48-57), the present studies were designed to assess the effect of
      modulating intracellular glutathione (GSH) content, on ROS generation, in the
      absence and presence of MeHg. Intracellular GSH was reduced by treatment with 100
      microM buthionine-L-sulfoxane (BSO) for 24 h, and increased by treatment with 1
      mM l-2-oxothiazolidine-4-carboxylic acid (OTC) for 24 h. Additionally, the
      effects of the selective antioxidants, catalase (1000 U/ml for 1 h), an H2O2
      scavenger, and n-propyl gallate (100 microM for 1 h), a superoxide radical (*O2-)
      and possibly hydroxyl radical (*OH) scavenger on MeHg-induced ROS formation were
      examined. After these treatments, astrocytes were exposed to +/-10 microM MeHg
      for 30 min, following which the fluorescent probes, CM-H2DCFA and CM-H2XRos were
      added; 20 min later, laser scanning confocal microscopy (LSCM) images were
      obtained. Exposure of astrocytes for 24 h to 100 microM BSO, a GSH synthesis
      inhibitor, led to a significant increase in mitochondrial ROS (i.e., *O2-, *NO,
      and ONOO-) formation, as assessed with CM-H2XRos mitotracker red dye. Similarly,
      BSO increased ROS formation in various intracellular organelles, as assessed with
      CM-H2DCFDA. BSO in combination with MeHg increased fluorescence levels in
      astrocytes to levels above those noted with BSO or MeHg alone, but this effect
      was statistically indistinguishable from either of these groups (BSO or MeHg).
      Pretreatment of astrocytes for 24 h with 1 mM OTC abolished the MeHg-induced
      increase in ROS. Results similar to those obtained with OTC were observed with
      the free radical scavenger, n-propyl gallate (n-PG). The latter had no
      significant effects on astrocytic fluorescence when administered alone. This *O2-
      and possibly *OH radical scavenger significantly attenuated MeHg-induced ROS
      formation. Catalase, an H2O2 scavenger, was less effective in reducing MeHg
      induced ROS formation. Taken together, these studies point to the important
      protective effect of adequate intracellular GSH content as well as antioxidants
      against MeHg-triggered oxidative stress in primary astrocyte cultures.

PMID- 15950755
TI  - In vivo transgene expression from an adenoviral vector is altered following a 6
      OHDA lesion of the dopamine system.
AB  - We have investigated the in vivo dynamics of an adenovirus-based, LacZ expressing
      vector, RAd36, at different doses, when injected unilaterally into the corpus
      striatum of normal rats. We have further investigated the characteristics of this
      vector in the presence of a 6-OHDA lesion of the nigrostriatal pathway. The
      dopamine-depleting lesion had an effect on both the number and the distribution
      of cells transduced by the adenoviral vector. The lesioned side of the brain
      contained significantly greater numbers of beta-galactosidase positive cells than
      the unlesioned side at 3 days, 1 week and 4 weeks post-injection and the
      distribution of transduced cells was altered by the presence of a dopamine
      lesion. We conclude that the increased levels of transgene expression seen in the
      lesioned hemisphere are due to a change in the diffusion characteristics of the
      injected vector in the lesioned hemisphere. These results indicate that, when
      investigating the use of virus-based vectors, ultimately for use in gene
      therapies in the CNS, the in vivo dynamics of the vector need to be assessed not
      only in the normal brain, but also in the pathological brain state such as animal
      models of target diseases.

PMID- 15950757
TI  - Heme deficiency suppresses the expression of key neuronal genes and causes
      neuronal cell death.
AB  - Defective heme synthesis may cause acute porphyrias, which are associated with a
      wide array of neurological disturbances involving both the central and peripheral
      nervous systems. Thus, the understanding of the roles of heme in neuronal cell
      function may provide insights into the molecular events underlying the
      pathogenesis of neuropathies associated with defective heme synthesis. In this
      report, we use rat pheochromocytoma (PC12) clonal cells as a model system for
      studying the role of heme in neuronal cell survival. We examined the effects of
      inhibition of heme synthesis on signaling pathways and gene expression in nerve
      growth factor (NGF)-induced PC12 cells. We found that succinyl acetone-induced
      heme deficiency selectively caused apoptosis in NGF-induced PC12 cells. Further,
      we found that in succinyl acetone-treated, NGF-induced cells, the pro-survival
      Ras-ERK1/2 signaling pathway was inactivated and the pro-apoptotic JNK signaling
      pathway was activated. In these cells, the activation of caspase and the cleavage
      of nuclear poly (ADP-ribose) polymerase (PARP) were also evident. Importantly,
      microarray gene expression analysis showed that more than 20 key neuronal genes
      that were induced by NGF were suppressed by succinyl acetone. These genes include
      those encoding survival motor neuron protein, synaptic vesicle protein SVOP, and
      neural cell adhesion molecule NCAM. These results indicate that heme is important
      for neuronal cell signaling and the proper functioning of neuronal cells.

PMID- 15950758
TI  - Regulation of ApoE receptor proteolysis by ligand binding.
AB  - Two brain receptors for apolipoprotein E (apoE), the apoE receptor 2 (apoEr2) and
      the very low density lipoprotein receptor (VLDLr), are important in neuronal
      migration during development. Using a series of tagged constructs, we found that
      these two receptors undergo extracellular cleavages to release secreted forms of
      the receptors and intramembranous cleavages to degrade the C-terminal fragments.
      Release of the extracellular domains was blocked by an inhibitor of
      metalloproteinases and increased by PMA. Accumulation of the intracellular domain
      was increased by the presence of an inhibitor of gamma-secretase. ApoE binding to
      these receptors caused increased release of the extracellular domain and
      accumulation of the intracellular domains; similar increases in receptor
      proteolytic domains were observed from endogenous apoEr2 after treatment of
      primary neurons or rat hippocampus with an apoE-derived peptide. The human apoE
      isoforms promoted proteolysis to different degrees, with apoE2 resulting in a
      greater accumulation of the C-terminal fragments of apoEr2 compared with apoE4.
      These effects of apoE on receptor proteolysis were mediated by the ligand binding
      domain of the receptor. Similar promotion of receptor cleavage was seen with two
      other ligands, reelin and activated alpha2-macroglobulin. We suggest that
      signaling promoted by these receptors depends in part on these regulated
      proteolytic events.

PMID- 15950759
TI  - Methamphetamine modulation of gene expression in the brain: analysis using
      customized cDNA microarray system with the mouse homologues of KIAA genes.
AB  - Amphetamine abuse may be associated with adaptive changes in gene expression. In
      the present study, we used a newly developed cDNA array system comprising mouse
      KIAA (mKIAA) cDNA clones to examine changes in gene expression after chronic
      methamphetamine (MAP) treatment. Mice were daily treated with saline or MAP (2
      mg/kg, ip) for 2 weeks. Approximately 800 mKIAA clones were blotted onto a nylon
      membrane and hybridized with 33P-labeled DNA derived from mRNAs from mouse whole
      brain. MAP-induced changes were found in several clones by using whole brain
      mRNA. Since gene expression of Per2, one of the period protein-related proteins,
      was the most affected by MAP treatment, its expression was further analyzed in
      pooled hippocampi from 20 mice that had been treated with saline or MAP (2 mg/kg,
      ip) for 2 weeks. The gene expression and protein expression of Per2 in the
      hippocampus were increased by MAP treatment. In the hippocampus, Per2 gene
      expression was under the regulation of circadian rhythm and increases in Per2
      expression were due to the phase shift induced by chronic MAP treatment. These
      findings suggest that unique expression changes of period protein-related
      proteins in the hippocampus occur in MAP abuse.

PMID- 15950760
TI  - Conditioned place preference associates with the mRNA expression of diazepam
      binding inhibitor in brain regions of the addicted rat during withdrawal.
AB  - The diazepam binding inhibitor (DBI) modulating the functions of the GABAA
      receptors is involved in the maladaptation of neural system during using opiate,
      but its role in opiate dependence is not fully understood. Using conditioned
      place preference (CPP) rat model and in situ hybridization technique, we examined
      the correlation between opiate dependence and the mRNA expression of DBI. We
      found that chronic morphine treatment enabled CPP and increased the DBI mRNA
      expression in crucial brain regions of addiction. Withdrawal for 3 days caused
      significant physical signs and further increased the DBI mRNA expression. Both
      the DBI mRNA and CPP expression remained significantly high but physical signs
      were at control level in the animals withdrawal for 6 days. Remarkably, the DBI
      mRNA expressions in the CA1 region of the hippocampus (CA1), ventral tagmental
      area (VTA), nucleus accumbens (NAc) and amygdala (AMG) were positively correlated
      to CPP during the periods from withdrawal for 3 days to withdrawal for 6 days.
      These findings suggest that DBI may play a role in both physical and
      psychological dependence of opiates.

PMID- 15950761
TI  - EGP-314 is expressed differentially in three brain zones at an early time in an
      experimentally induced ischemia rat model.
AB  - Gene expression in frontal, occipital, and hippocampal regions of rat brains at
      15 min of ischemic injury was studied in a rat model by producing focal cerebral
      ischemia through middle cerebral artery (MCA) occlusion without reperfusion.
      Catalase, epithelial glycoprotein (EGP-314), cytochrome C oxidase-subunit 1,
      ribosomal L31 protein, and ceruloplasmin were found to be differentially
      expressed. Specific primers were designed to study this newly reported brain EGP
      314, a cellular adhesion molecule involved in cell-cell and cell-extracellular
      matrix interactions and related with cytoskeletal organization, differentiation,
      and proliferation. In the frontal and occipital lobes, EGP-314 expression was low
      in control and ischemic conditions and increased in sham injured conditions,
      whereas in the hippocampal region its expression was induced only by ischemia. In
      situ hybridization and immunohistochemistry revealed that EGP-314 mRNA and the
      protein were present in the ischemic hippocampus pyramidal neurons. DNA
      fragmentation was demonstrated by TUNEL and LM-PCR analysis in hippocampus
      region. TUNEL positive pyramidal neurons were observed at 15 min of ischemia. DNA
      ladder was found at 12 and 15 min of ischemia.

PMID- 15950762
TI  - A new strain of rat for functional analysis of PINA.
AB  - Long Evans cinnamon (LEC) rat is an animal model for human Wilson disease (WD)
      due to a deletion in Atp7b, the copper transporter defective in WD patients.
      Previously, we have demonstrated presence of an alternative product termed PIneal
      Night-specific ATPase (PINA) generated by an intronic promoter in Atp7b gene.
      Analysis of LEC rat in this study demonstrates that PINA is absent in the LEC
      pineal establishing its usefulness for investigating PINA function. Studies of
      the LEC pineal, however, revealed an additional defect in serotonin N
      acetyltransferase (NAT), the key enzyme in melatonin production. Linkage studies
      confirm that the NAT phenotype is entirely independent of PINA mutation in the
      pineal gland of LEC rats, and sequence analysis demonstrates that NAT defect is
      due to a point mutation in NAT coding region. In addition, we demonstrate that
      the cinnamon coat color of the LEC rat is unlinked to PINA and NAT deficiencies
      in these animals. To facilitate further functional analysis of PINA in pineal
      physiology, we crossed LEC rats with PVG rats that are wildtype for PINA, NAT and
      coat color, and obtained rats that are defective only in PINA/Atp7b locus (termed
      LPP rats) and normal for NAT activity and coat color. Furthermore, we have
      identified the deletion breakpoint of Atp7b gene in LPP rats, which allows
      simplified genotyping of mutant animals. The separation of PINA mutation from
      both NAT and coat color mutations in the new LPP rats will permit better
      functional studies of PINA in pineal circadian physiology.

PMID- 15950763
TI  - Abnormal intracellular trafficking of high affinity nerve growth factor receptor,
      Trk, in stable transfectants expressing presenilin 1 protein.
AB  - The pathogenesis of Alzheimer's disease (AD) is now thought to be tightly linked
      to Abeta deposition and oxidative stress, but it is still unknown how these
      factors result in neuronal dysfunction and cell death. Mutations of presenilin 1
      (PS1) gene are the causative gene for early onset familial AD (FAD) due to the
      overproduction and deposition of pathogenic Abeta1-42 peptides. We report here
      the molecular influences of the overexpression of PS1 protein by stable
      transfection of PS1 cDNA into SH-SY5Y neuroblastoma cells on the function of high
      affinity nerve growth factor receptor, Trk, that is essential for neuronal
      survival and differentiation. We examined the sensitivity of these transfectants
      to oxidative stress and found that mutant (I143T) PS1-expressing clones showed
      the highest vulnerability to an oxidative stress inducer, hydrogen peroxide
      treatment compared with that of mock-transfected clones, whereas wild PS1
      expressing cells were less vulnerable to the treatment than mutant PS1
      transfectants. Because nerve growth factor (NGF) is known to protect neuronal
      cells from oxidative stress-induced cell death, we examined the NGF-Trk-mediated
      intracellular signaling pathway in these transfectants. In the wild and mutant
      PS1 cDNA-transfected cells, NGF did not elicit the autophosphorylation response
      of Trk, although their basal levels of tyrosine phosphorylation were higher than
      those of mock-transfected cells. Immunocytochemical and subcellular fractionation
      studies revealed that most of Trk proteins are abnormally located in the
      cytoplasm as well as in the nucleus in PS1-overexpressing clones irrespective of
      wild and mutant forms. These results strongly indicate that the expression level
      of PS1 protein has a cross talk with the Trk-dependent neuroprotective
      intracellular signaling pathway.

PMID- 15950764
TI  - Functional endothelin ET B receptors are selectively expressed in human
      oligodendrogliomas.
AB  - Endothelin-1 (ET-1), a vasoactive and mitogenic peptide mainly produced by
      vascular endothelial cells, may be involved in the progression of several human
      tumors. Here, we present an immunohistochemical analysis of the expression
      pattern of ET-1 receptor subtypes (ET(A)-R and ET(B)-R) and a functional study of
      their potential role in human oligodendrogliomas and oligoastrocytomas. By
      comparison, we assessed the corresponding expression patterns of glioblastomas.
      Interestingly, a nuclear localization of ET-1 receptor subtypes (associated or
      not with a cytoplasmic labeling) was constantly observed in tumor cells from all
      three glioma types. Moreover, we noted a distinct receptor distribution in the
      different gliomas: a nuclear expression of ET(B)-R by tumor cells was found to be
      restricted to oligodendrogliomas and oligoastrocytomas, while a nuclear
      expression of ET(A)-R was only detected in tumor cells from some glioblastomas.
      Using primary cultures of oligodendroglial tumor cells, we confirmed the
      selective expression of nuclear ET(B)-R, together with a plasma membrane
      expression, and further demonstrated that this receptor was functionally coupled
      to intracellular signaling pathways known to be involved in cell survival and/or
      proliferation: extracellular signal-regulated kinase and focal adhesion kinase
      activation, actin cytoskeleton reorganization. In addition, impairment of ET(B)-R
      activation in these cells by in vitro treatment with an ET(B)-R-specific
      antagonist induced cell death. These data point to ET-1 as a possible survival
      factor for oligodendrogliomas via ET(B)-R activation and suggest that ET(B)-R
      specific antagonists might constitute a potential therapeutic alternative for
      oligodendrogliomas.

PMID- 15950765
TI  - Molecular characterization of two novel splice variants of G alphai2 in the rat
      vestibular periphery.
AB  - GTP binding proteins play an important role in mediating signals transduced
      across the cell membrane by membrane-bound receptors. We previously described a
      partial sequence, termed Galphai2vest, obtained from rat vestibular tissue that
      was nearly identical to rat Galphai2. Using an experimental strategy to further
      characterize Galphai2vest (GenBank accession number AF189020) and identify other
      possible Galphai2-related transcripts expressed in the rat vestibular periphery,
      we employed a RecA-based gene enrichment protocol in place of conventional
      library screening techniques. We identified two novel Galphai2 splice variants,
      Galphai2(a) (GenBank accession number AY899210) and Galphai2(b) (GenBank
      accession number AY899211), that have most of exons 8 and 9 deleted, and exons 5
      through 9 deleted, respectively. In situ hybridization studies were completed to
      determine the differential expression of Galphai2 between the vestibular primary
      afferent neurons and the vestibular end organs. Computer modeling and predicted
      3D conformation of the wild type Galphai2 and the two splice variants were
      completed to evaluate the changes associated with the Gbetagamma and GTP binding
      sites. These two novel alternatively spliced isoforms of Galphai2 putatively
      encode truncated proteins that could serve unique roles in the physiology of the
      vestibular neuroepithelium. Galphai2vest was found to be a processed pseudogene.

PMID- 15950766
TI  - Possible association of p53 codon 72 polymorphism with susceptibility to adult
      and pediatric high-grade astrocytomas.
AB  - Polymorphisms in codon 72 of the p53 tumor suppressor gene have been associated
      with susceptibility to human cancer. We wished to evaluate whether variant
      allelic forms of the p53 protein were associated with brain tumors. In this
      study, we scored 135 brain tumor samples (92 adult and 43 pediatric cases
      consisting of 64 high-grade astrocytomas and 71 non-astrocytomas) for the P53
      Arg72Pro polymorphisms. Our data show that the genotype frequencies of P53
      Arg72Pro vary not only between patients with brain tumors and controls, but also
      between different histological subtypes of brain tumors. Specifically, we found
      (i) that the genotype distributions of the P53 Arg72Pro between all brain tumors
      and controls were statistically significant (P < 0.001) as well as their variant
      allele frequencies between cases and controls (P < 0.001); (ii) that there was a
      significant increase in the Arg/Pro heterozygous genotype among high-grade
      astrocytomas compared with non-astrocytomas (P = 0.002); and (iii) that there was
      a significant increase in the Arg/Pro heterozygous genotype among high-grade
      astrocytomas containing transdominant as well as recessive p53 mutations compared
      with controls (P = 0.002). Our results suggest a possible association between P53
      Arg72Pro polymorphisms and susceptibility to brain tumors, particularly high
      grade astrocytomas.

PMID- 15950767
TI  - Quantitative analysis of tau isoform transcripts in sporadic tauopathies.
AB  - A number of neurodegenerative diseases, including Alzheimer's disease (AD), are
      characterized by intraneuronal accumulation of the tau protein. Some forms of
      FTDP-17 are caused by mutations in the tau gene affecting exon 10 splicing.
      Therefore, dysregulation of tau pre-mRNA splicing may be a contributing factor to
      sporadic tauopathies. To address this question, we devised a real-time RT-PCR
      strategy based on the use of a single fluorogenic probe to evaluate the ratio
      between tau isoforms containing or lacking exon 10 (4R/3R ratio) in post-mortem
      brain samples. We found a two- to six-fold increase in the 4R/3R ratio in cases
      of FTDP-17 linked to a splice site mutation, hence confirming the validity of the
      strategy. The difference in the 4R/3R ratio in the superior temporal and superior
      frontal gyri between AD and control brains was not statistically significant.
      Similarly, there was no significant difference in the 4R/3R ratio between Pick's
      disease cases and controls, indicating that the predominance of tau3R protein in
      PiD reflects post-translational modifications of specific isoforms. This study
      indicates that post-translational events are likely to be the main factors
      controlling tau isoform composition in sporadic tauopathies and highlights the
      benefit of quantitative RT-PCR in the assessment of splicing abnormalities in
      tauopathies.

PMID- 15950768
TI  - Improved representation of gene markers on microarray by PCR-Select subtracted
      cDNA targets.
AB  - Despite the success and popularity of microarrays as a high-throughput technology
      for gene-expression studies, its sensitivity is as yet fairly limited. We have
      successfully combined the use of PCR-Select cDNA subtraction and Affymetrix
      GeneChips (AGC) to identify differentially expressed gene markers. Total RNA
      (totRNA) from combined hippocampus and cerebellum tissues of 2-week-old rat pups
      maintained for 5 weeks on an n-3 fatty acid (FA) deficient diet supplied to dams
      was isolated, SMART-amplified, and used for PCR-Select subtraction versus an
      adequately fed control litter preparation. Subtracted and amplified ds-cDNA end
      products were fragmented, terminally labeled with biotin-ddUTP and hybridized
      with RN-U34A AGC. At least 10-fold more potential gene markers with log2(T/D) >
      or = 1.4 were found versus the traditional AGC technology when the same chip was
      tested using nonsubtracted targets. Of this set of markers, 30% were robustly
      validated by real-time relative RT-PCR (rtrRT-PCR) and grouped as "confirmed"
      markers while the remaining were ascribed as "latent" markers. An improved and
      universal protocol to provide a rapid assessment for gene profiling in biological
      specimens is indicated.

PMID- 15950769
TI  - Experimental subarachnoid hemorrhage induces changes in the levels of hippocampal
      NMDA receptor subunit mRNA.
AB  - NMDA receptors may play a crucial role in nerve cell death following subarachnoid
      hemorrhage (SAH). Changes in NMDA receptor-mediated transmission appear before
      neuronal death in rodent models of transient ischemia, and NMDA receptor function
      is known to be dependent on subunit composition. Here, we have investigated
      whether mRNA expression of the NMDA receptor subunits is altered in the
      hippocampal formation 3-5 h following experimental SAH, and correlated these
      early alterations to subsequent delayed cell death. SAH was induced by
      intraluminal perforation of the internal carotid artery intracranially, and
      cerebral blood flow (CBF) was bilaterally monitored by laser-Doppler flowmetry.
      Early changes in NMDA receptor subunit mRNA and early nerve cell death were
      analyzed at 3-5 h after SAH, and delayed nerve cell death was analyzed at 2-7
      days after SAH. Duration of ipsilateral CBF reduction below 30% of baseline
      (CBF30) was predictive of ipsilateral delayed nerve cell death in the CA1 2-7
      days after SAH. At CBF30 > 9 min, we found downregulation of mRNA for NR2A, NR2B,
      and NR3B at 3-5 h after SAH, whereas the levels of NR1 mRNA were unaffected. The
      downregulation of NR2A and NR2B mRNA may result in a reduced NMDA receptor
      function. Such reduction may be sufficient to provide neuroprotection in the
      dentate gyrus, where no cell death appears, but insufficient to rescue neurons in
      the hippocampus proper following SAH.

PMID- 15950770
TI  - Geldanamycin activates Hsp70 response and attenuates okadaic acid-induced
      cytotoxicity in human retinal pigment epithelial cells.
AB  - Reversible protein phosphorylation regulates the biological activities of many
      human proteins involved in crucial cellular processes, e.g., protein-protein
      interactions, cell signaling, gene transcription, cell growth, and death. A
      malfunction of cellular homeostasis in retinal pigment epithelial (RPE) cells is
      involved in the age-related retinal degeneration. In this study, we examined
      cytotoxicity in human RPE cells subjected to the protein phosphatase inhibitor,
      okadaic acid (OA). Moreover, the influence of Hsp90 inhibitor geldanamycin (GA),
      a benzoquinone ansamycin, in cytoprotection was assessed. Hsp70 protein levels
      were analyzed by Western blot. Cellular viability was determined by LDH and MTT
      assays. To study apoptotic cell death, caspase-3 enzyme activity was measured by
      assaying the cleavage of a fluorescent peptide substrate and Hoechst dye was used
      to visualize nuclear morphology. OA treatment caused morphological changes and
      induced cytotoxicity by caspase-3-independent manner in the RPE cells. No
      evidence of nuclear fragmentation was observed in response to OA. Interestingly,
      GA treatment accumulated Hsp70 protein and attenuated OA-induced cytotoxicity.
      This study suggests that Hsp70 and Hsp90 are closely related to cytoprotection of
      RPE cells in response to protein phosphatase inhibition.

PMID- 15950771
TI  - Identification and distribution of mouse carboxypeptidase A-6.
AB  - Carboxypeptidase A-6 (CPA6) was recently discovered in the human genome. To gain
      information regarding the potential function of this novel protein, the mouse
      homolog of CPA6 was identified using a combination of bioinformatics and reverse
      transcriptase-polymerase chain reaction (RT-PCR). In addition, homologs in rat,
      chicken, and frog were identified using a bioinformatics approach. The
      distribution of CPA6 mRNA in mouse tissues was examined using RT-PCR and in situ
      hybridization. A strong RT-PCR signal is detectable in olfactory bulb, and much
      lower levels are present in other regions such as the cerebral cortex,
      hippocampus, hypothalamus, striatum, and medulla. In peripheral tissues, a
      moderate RT-PCR signal is present in epididymis, and low levels are detectable in
      colon and spleen. The high level of CPA6 in adult mouse brain olfactory bulb was
      confirmed by in situ hybridization. Lower levels of CPA6 mRNA were found to be
      present in the cingulate cortex, lateral septum, pontine nucleus, and inferior
      olivary nucleus of the hindbrain. Within the olfactory bulb, CPA6 mRNA is
      enriched in the mitral and granular layer. A lower level of CPA6 mRNA is present
      in the internal and external plexiform layers, and no signal is detectable in the
      olfactory nerve layer. The distribution was also examined in whole embryos at
      embryonic day 14.5 and CPA6 mRNA was found to be enriched in eye, ear,
      osteoblasts, stomach, skin, dorsal root ganglia, and throughout the CNS. The
      presence of CPA6 mRNA in the rectus muscle layer of the eye at embryonic day 14.5
      is consistent with the observation that the CPA6 gene is disrupted in a patient
      with Duane syndrome, a congenital eye defect. Taken together, the distribution of
      CPA6 suggests a specific role in a limited number of tissues, and it is possible
      that this role involves an aspect of cell migration.

PMID- 15950772
TI  - APeg3, a novel paternally expressed gene 3 antisense RNA transcript specifically
      expressed in vasopressinergic magnocellular neurons in the rat supraoptic
      nucleus.
AB  - Vasopressin (VP) and oxytocin (OT) play critical roles in the regulation of salt
      and water balance, lactation, and various behaviors and are expressed at very
      high levels in specific magnocellular neurons (MCNs) in the hypothalamo
      neurohypophysial system (HNS). In addition to the cell-specific expression of the
      VP and OT genes in these cells, there are other transcripts that are
      preferentially expressed in the VP or OT MCNs. One such gene, paternally
      expressed gene 3 (Peg3), is an imprinted gene expressed exclusively from the
      paternal allele that encodes a Kruppel-type zinc finger-containing protein
      involved in maternal behavior and is abundantly expressed in the VP-MCNs. We
      report here the robust expression in the VP-MCNs of an RNA, which we designate
      APeg3 that is transcribed in the antisense direction to the 3' untranslated
      region of the Peg3 gene. The APeg3 mRNA is about 1 kb in size, and the full
      length sequence of APeg3, as determined by 5' and 3' RACE, contains an open
      reading frame that predicts a protein of 93 amino acids and is predominantly
      expressed in VP-MCNs. Both Peg3 and APeg3 gene expression in the VP-MCNs increase
      during systemic hyperosmolality in vivo, demonstrating that both of these genes
      are osmoregulated.

PMID- 15950773
TI  - Involvement of phosphorylated extracellular signal-regulated kinase in the mouse
      substance P pain model.
AB  - In the present study, we investigated the role of pERK in nociceptive processing
      at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain
      model. In the immunoblot assay, intrathecal (it) injection with SP increased pERK
      level at the spinal cord and an immunohistochemical study showed that increase of
      pERK immunoreactivity mainly occurred in the lamina I and II areas of the spinal
      dorsal horn. At the supraspinal level, pERK was increased in hippocampus and
      hypothalamus by i.t. SP injection, and an increase of pERK immunoreactivity
      mainly occurred in the dentate gyrus and CA3 region of hippocampus and
      paraventricular nucleus on hypothalamus. The nociceptive behavior induced by Sub
      P administered either i.t. or intracerebroventricularly (i.c.v.) was attenuated
      by PD98059 (a MEK 1/2 inhibitor) in a dose-dependent manner. Our results suggest
      that pERK located at both spinal cord and supraspinal levels plays as an
      important regulator during the nociceptive process activated by SP administered
      it.

PMID- 15950774
TI  - Cytokine mRNA levels in brain and peripheral tissues of the rat: relationships
      with plus-maze behavior.
AB  - There is evidence that interleukin (IL)-2 may be related to anxiety as measured
      in the elevated plus-maze. Recently, we showed that normal adult male Wistar rats
      can differ systematically in this test of avoidance behavior, that is, time spent
      on the open arms of the elevated plus-maze. Rats with low open arm time had
      higher striatal levels of IL-2 mRNA than those with high open arm time, but did
      not differ significantly in expression of other striatal cytokine mRNA. Here, we
      investigated whether these expression effects are anatomically specific to the
      striatum. Therefore, we asked in this double-blind study whether elevated plus
      maze behavior may also be related to endogenous levels of cytokine mRNA in other
      brain regions, which play a role for anxiety, namely the amygdala, hippocampus,
      and the prefrontal cortex. Additionally, and as peripheral controls, immuno-neuro
      endocrine relevant tissues (adrenal glands, spleen) were analyzed. Based on open
      arm time in the elevated plus-maze, male Wistar rats were divided into sub-groups
      with either low or high open arm time behavior. Then, IL-1beta, IL-2, IL-6, and
      tumor necrosis factor (TNF)-alpha cDNA levels were measured post-mortem using
      semi-quantitative, competitive, reverse transcription polymerase chain reaction.
      First, we found that cytokine expressions differed considerably between and
      within these central and peripheral tissues. Secondly, rats with high compared to
      low open arm time behavior showed higher IL-2 mRNA levels in the prefrontal
      cortex, which is an inverse pattern to what we recently found in the striatum.
      These results provide new evidence indicating that cytokine mRNA in the brain can
      be related to elevated plus-maze behavior and that this relationship is site
      (prefrontal cortex, striatum)- and cytokine mRNA-specific (IL-2).

PMID- 15950775
TI  - Evidence of involvement of the nNOS and the kappa-opioid receptor in the same
      intracellular network of the rat periaqueductal gray that controls morphine
      tolerance and dependence.
AB  - Tolerance and dependence are the most important side effects of opioid-mediated
      pain therapies. However, the mechanisms through which these phenomena are
      produced still remain unknown. Among the opioid receptors, the kappa-opioid
      receptor has been the focus of strong research efforts, since it contributes to
      the reversal of morphine-induced tolerance and dependence. Parallel to this,
      neuronal nitric oxide synthase has been shown to play a key role in the
      development of these unwanted effects. Both the kappa-opioid receptor and
      neuronal nitric oxide synthase are abundantly located in the CNS. One of the
      areas where these cellular agents are best represented is a key encephalic
      nucleus in the development of tolerance to the analgesic action of opioid drugs,
      the periaqueductal gray. In this work, we studied whether morphine-induced
      tolerance and dependence causes changes (a) in the activity of neuronal nitric
      oxide synthase and (b) in kappa-opioid receptor expression in the rat
      periaqueductal gray. Besides, we examined the colocalization of both molecules.
      Our results point to an involvement of KOR and nNOS in the same intracellular
      network that controls the development of morphine tolerance and dependence.

PMID- 15950776
TI  - Alternative splicing and promoter use in the human GABRA2 gene.
AB  - GABA(A) receptors mediate the majority of the fast synaptic inhibition in the
      mammalian brain. They are the targets of several important drugs, including
      benzodiazepines, which are used as anxiolytics, sedatives, anti-convulsants, and
      in the treatment of alcohol withdrawal symptoms. Non-coding variations in GABRA2,
      the gene encoding the alpha2 subunit, are associated with the risk for
      alcoholism, suggesting that regulatory differences are important. GABRA2 mRNAs
      from whole human brain and from three brain regions were examined for evidence of
      alternative splicing using reverse transcription-PCR and DNA sequencing. A
      complex pattern of alternative splicing and alternative promoter use of the human
      GABRA2 mRNA was demonstrated. There are four major isoforms consisting of
      combinations of two alternative 5' and 3' exons, as well as minor isoforms
      lacking exon 4 or exon 8. The alternative 5' exons each lie downstream of a
      functional promoter sequence, as shown by transient transfection assays. The
      promoter activities of naturally occurring haplotypes differed, indicating
      genetic differences in gene expression.

PMID- 15950777
TI  - Molecular reactivity of mesocorticolimbic brain areas of high and low grooming
      rats after elevated plus maze exposure.
AB  - High and low grooming rats (HG and LG), selected by extremities in stress-induced
      self-grooming on the elevated plus maze (EPM), display differences in stress
      coping style on the EPM, their motivation to self-administer cocaine, and
      differences in the reactivity of dopaminergic nerve terminals in
      mesocorticolimbic brain areas. This indicates a link between coping with a
      stressful/anxiogenic situation and drug intake. Here, we aimed to determine the
      molecular correlates of these differences by analyzing the reactivity of the
      mesocorticolimbic brain areas (the medial prefrontal cortex (mPFC) nucleus
      accumbens shell (NAS) and ventral tegmental area (VTA)) of HG and LG rats in
      response to EPM exposure. We report by measuring levels of immediate early gene
      (IEG) transcripts that EPM exposure-induced IEG expression was not significantly
      different between HG and LG rats. On the other hand, novel IEG expression
      patterns upon stress (EPM exposure) were apparent in all three areas including
      arc induction in the mPFC and NAS, CRH, BDNF, and Nr4a3 induction in the NAS, and
      serum glucocorticoid-regulated kinase (sgk) induction in the VTA. It is concluded
      that although the mPFC, NAS, and VTA play a role in modulating stress and
      grooming behavior, the neuronal reactivity in these regions measured by the IEG
      response is not related with behavioral extremities in stress coping style
      displayed on the EPM.

PMID- 15950778
TI  - Inhibition of GSK3beta is a common event in neuroprotection by different survival
      factors.
AB  - Depolarizing concentrations of potassium (HK, 25 mM), cyclic AMP elevating agents
      and analogs (cAMP), insulin-like growth factor-1 (IGF-1), or lithium can maintain
      the survival of cultured rat cerebellar granule neurons (CGNs). We investigated
      the possibility that the signal transduction pathways utilized by these four
      survival factors converge in regulating a common molecular target. We targeted
      the regulation of the kinase GSK3beta as the critical event in the survival
      directed by the four survival factors. We found that treatment of CGNs with HK,
      the cAMP-elevating agent forskolin, IGF-1, and lithium resulted in
      phosphorylation of GSK3beta at serine-9 and thus its inactivation. Furthermore,
      pharmacological inhibition of core components in the survival signaling cascades
      initiated by HK, forskolin, IGF-1, and lithium causes apoptosis and activation of
      GSK3beta accompanies this death. Finally, we examined the pharmacological
      inhibitors of GSK3beta, GSK3 inhibitor I, TDZD-8, and SB-415286, for their
      ability to prevent low potassium (LK)-induced apoptosis. Although previous
      reports demonstrate inhibition of GSK3beta in in vitro kinase assays with GSK3
      inhibitor I and TDZD-8, we were unable to detect inhibition of GSK3beta in
      neuronal cultures treated with these compounds and thus no protection from LK
      induced apoptosis. SB-415286 on the other hand, was able to rescue CGNs from cell
      death. Taken together, we conclude that regulation of GSK3beta is a critical
      convergence event in the promotion of CGN survival by different factors.

PMID- 15950779
TI  - Regulation of the cyclooxygenase-2 system by interleukin-1beta through mitogen
      activated protein kinase signaling pathways: a comparative study of human
      neuroglioma and neuroblastoma cells.
AB  - Glial activation and inflammation following brain injury may initiate and
      maintain the process of neurodegeneration. Both glia and neurons synthesize
      proinflammatory mediators such as interleukin 1 beta (IL-1beta), cytosolic
      phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandins. The
      molecular mechanisms by which IL-1beta regulates inflammatory genes such as cPLA2
      and COX-2 in glial and neuronal cells are poorly understood. We have studied IL
      1beta-mediated gene regulation in an established glial and neuronal human cell
      lines. We report that IL-1beta induced cPLA2 and COX-2 mRNA and protein
      expression and subsequent prostaglandin E2 (PGE2) release in a time-dependent
      manner in H4 neuroglioma cells. Both SB203580 and PD98059 [p38 and p42/44 mitogen
      activated protein kinase (MAPKs) inhibitors, respectively] reduced IL-1beta
      induced PGE2 production, while only SB203580 reduced both cPLA2 and COX-2
      expression. Similarly, in SKNSH neuroblastoma cells, both SB203580 and PD98059
      reduced IL-1beta-induced PGE2 release, with no detectable COX-2 and cPLA2 protein
      expression in these cells. Our results indicate that the signaling mechanisms of
      p38 and p42/44 MAPKs play a role in IL-1beta-mediated PGE2 release in both of
      these cell lines, with differences upstream at the level of cPLA(2)/COX-2
      expression. IL-1beta-induced cPLA2 and COX-2 gene expression is modulated through
      the p38 MAPK pathway in both neuroglioma and neuroblastoma cells. Understanding
      the signaling mechanisms involved in IL-1beta-mediated inflammatory processes in
      both glia and neuronal cells may provide potential targets for therapeutic
      intervention for neurological disorders.

PMID- 15950780
TI  - Interleukin-1beta induces CREB-binding protein (CBP) mRNA in brain and the
      sequencing of rat CBP.
AB  - Interleukin-1 beta (IL-1) and CREB have many CNS actions including sleep
      regulation and hippocampal-dependent learning. CREB acts in part via CREB-binding
      protein (CBP). We thus determined whether IL-1 could induce CBP gene expression.
      Initially, cultured hippocampal cells were treated with IL-1 and differential
      display reverse transcription was used to identify up- and down-regulated genes.
      We then sequenced rat CBP. Of the IL-1-upregulated genes, CBP and adenine
      nucleotide translocator-1 (ANT-1) were investigated in vivo. In these
      experiments, IL-1 was given to rats intraventricularly and sacrificed 2 h later;
      both CBP and ANT-1 transcripts were upregulated in the cerebral cortex and
      hypothalamus. We conclude that rat CBP shares many of the functional domains as
      human and murine CBP and that IL-1 upregulates genes previously associated with
      learning and sleep.

PMID- 15950781
TI  - Neuroprotection mediated by subtoxic dose of NMDA in SH-SY5Y neuroblastoma
      cultures: activity-dependent regulation of PSA-NCAM expression.
AB  - The NMDA class of glutamate receptors plays a critical role in CNS, such as
      synaptic plasticity, axonal sprouting, growth, and migration. NMDA receptor
      stimulation has been shown to regulate polysialylated neural cell adhesion
      molecule (PSA-NCAM) expression in glial cell cultures and in hippocampal slice
      cultures. There is also growing evidence that molecular chaperons and ROS are
      related to the synaptic plasticity phenomena. We have examined the
      neuroprotective effect of subtoxic dose of NMDA in retinoic acid differentiated
      SH-SY5Y neuroblastoma cells. SH-SY5Y cell line differentiated with retinoic acid
      (10 muM) was exposed to NMDA (100 microM) or to antagonist MK-801 (200 nM) + NMDA
      and cells harvested after 24 h of treatment for PSA-NCAM, NCAM, and HSP70
      expression study and for biochemical analysis. A significant increase was
      observed in PSA-NCAM, NCAM-180, NCAM-140, and HSP70 expression as seen by Western
      blotting and immunocytofluorescent studies in NMDA-treated cultures. Biochemical
      analysis revealed a significant increase in the activities of glutathione
      peroxidase (GPx) and copper zinc-superoxide dismutase (CuZnSOD) upon exposure to
      NMDA. No significant change was observed in the level of lipid peroxidation. All
      the changes observed reverted back to the control values upon pretreatment of
      cultures with MK-801, a non-competitive NMDA receptor antagonist, prior to NMDA
      exposure indicating the involvement of NMDA receptor in these changes. These
      results illustrate the neuroprotective role of subtoxic dose of NMDA in SH-SY5Y
      neuroblastoma cells.

PMID- 15950782
TI  - Cloning and characterization of the chick NMDA receptor subunit-1 gene.
AB  - The N-methyl-D-aspartate family of glutamate receptors (NMDARs) are tetrameric
      cation channels including NR1, NR2, and possibly NR3 subunits. The physiological
      properties of the receptor are directly related to the subunit composition of the
      oligomer. Whereas NR1 is essential for the formation of functional channels, NR2
      and NR3 play a modulatory role. This work reports, for the first time, the
      cloning of a non-mammalian NR1 gene, including the 5'-regulatory region. The
      chick gene spans 31 kb of genomic DNA sequence composed of 22 exons interrupted
      by 21 introns. The exon/intron organization and the deduced amino acid sequence
      up to the end of exon 19 showed 85% homology to mammalian NR1 cloned genes.
      Significant differences from mammals were found at the C-terminal region which in
      the chick gene, includes a novel exon (exon 20) previously identified at the mRNA
      level in the chick retina. The basal promoter activity was shown to reside within
      the proximal 377 bp of 5'-regulatory region. The transcriptional activity of the
      5'-flanking region of the chick NR1 gene was shown to be higher in neuronally
      differentiated PC12 cells and in chick retinal neurons, than in non
      differentiated PC12 cells and Muller glia. Comparison of the 5'-flanking region
      of chick NR1 gene with mammalian NR1 genes suggests that, in spite of significant
      differences in the nucleotide sequence, they share common DNA binding sites such
      as RE1, SP1, AP2, CREB, NFkappaB, and MEF2; therefore, some of the molecular
      mechanisms involved in transcriptional regulation of NR1 gene expression could be
      conserved among species.

PMID- 15950783
TI  - Five mutations in the GABA A alpha6 gene 5' flanking region are associated with a
      reduced basal and ethanol-induced alpha6 upregulation in mutated Sardinian
      alcohol non-preferring rats.
AB  - The presence of four nucleotide changes and a three base-pair deletion in the
      GABA A alpha6-subunit promoter is described in Sardinian alcohol non-preferring
      rats, selectively bred for their ethanol aversion. These mutations are associated
      with the R100Q alpha6 intragenic mutation that was previously characterized in
      the same animals. The possibility that these mutated nucleotides alter the
      ethanol-induced upregulation of the alpha6 gene was investigated by measuring
      cerebellar alpha6 mRNA levels after a chronic ethanol liquid diet in sNP rat.
      Real-time quantitative PCR showed an increased alpha6 gene expression after
      ethanol ingestion in normal and mutated rats. However, lower amounts of alpha6
      mRNA levels were detected both in control and in ethanol-treated sNP rats
      carrying the five promoter and the intragenic mutations in a homozygous state.
      Using the electromobility shift assay, specific DNA binding sites were found in
      cerebellar extracts of the alpha6 regions comprising the five mutations. These
      results suggest that one or more of the mutated binding sites that were found in
      the 5' flanking alpha6 region may be a consensus sequence for regulatory factors
      which are responsible for both basal and ethanol-induced alpha6 gene expression.

PMID- 15950785
TI  - Expression of BLT1 leukotriene B4 receptor on the dorsal root ganglion neurons in
      mice.
AB  - We investigated using mice whether dorsal root ganglion (DRG) neurons express
      leukotriene B4 receptors. BLT1, but not BLT2, receptor mRNA was expressed in the
      DRG. Leukotriene B4 increased intracellular Ca2+ concentration in cultured DRG
      neurons, which was inhibited by leukotriene B4 antagonist. Many BLT1
      immunoreactive neurons were small in size and positive for TRPV1. BLT1
      immunoreactive fibers are present in the skin. The results suggest the expression
      of functional BLT1 receptors in the sensory neurons.

PMID- 15950784
TI  - Immediate withdrawal from chronic "binge" cocaine administration increases mu
      opioid receptor mRNA levels in rat frontal cortex.
AB  - An increase in preprodynorphin (ppdyn) mRNA was detected in the caudate putamen
      of chronically cocaine-treated and 3-h withdrawn rats. An increase in mu-opioid
      receptor (MOP) mRNA levels was observed in the frontal cortex of 3-h withdrawn
      rats. Naloxone had no effect on the increase of MOP or ppdyn mRNA levels. The
      results indicate that the opioid system is altered during early withdrawal from
      chronic cocaine administration.

PMID- 15950786
TI  - Differential mRNA expression of neurotrophic factors GDNF, BDNF, and NT-3 in
      experimental herpes simplex virus encephalitis.
AB  - Glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic
      factor (BDNF), and neurotrophin-3 (NT-3) mRNA levels were studied in the course
      of murine herpes simplex virus encephalitis. Induction of GNDF and NT-3 (both P <
      0.05) was found during acute encephalitis. Despite absence of clinical
      impairment, both neurotrophic factors were overexpressed 2 months (NT-3) and 6
      months (GDNF) following infection (both P < 0.05). Neurotrophic factors play an
      important role in neuronal survival and recovery after acute injury to the
      central nervous system (CNS) and may represent an additional therapeutic target
      for treatment of viral encephalitis.

PMID- 15950788
TI  - Proceedings of the IASLC Mesothelioma Workshop, September 29-October 2, 2004,
      Ermatingen, Switzerland.

PMID- 15950787
TI  - ADAM9, ADAM10, and ADAM15 mRNA levels in the rat brain after kainic acid-induced
      status epilepticus.
AB  - ADAM metalloprotease-disintegrins mediate cell adhesion, proteolytic processing,
      and signal transduction. In the present study, the mRNA levels of ADAM9, ADAM10,
      and ADAM15 were examined in rat brain after kainic acid (KA)-induced status
      epilepticus. ADAM9 and ADAM10 expression was induced in dentate gyrus of
      hippocampus. ADAM15 expression remained unchanged. The spatiotemporal expression
      of ADAM9 and ADAM10 suggests that their regulation after the KA-induced status
      epilepticus could be related to neuroprotection.

PMID- 15950789
TI  - Soluble mesothelin-related protein--a blood test for mesothelioma.
AB  - Identification of tumor marker for mesothelioma (MM) might prove useful in
      diagnosis as well as for monitoring tumor in response to therapy and for
      screening at-risk individuals. We tested the hypothesis that soluble mesothelin
      related protein (SMRP), a mesothelin family member, in the serum would be such a
      marker. Our data show that determination of SMRP in serum is a marker of MM with
      a sensitivity of sensitivity 83% and specificity 95% in the first 48 MM patients
      tested. Changes in serum SMRP levels parallel clinical course/tumor size and SMRP
      is elevated in 75% of patients at diagnosis. SMRP should also be useful for
      monitoring disease progression, and importantly, may prove useful for screening
      asbestos-exposed individuals for early MM.

PMID- 15950790
TI  - Clinical trials in malignant pleural mesothelioma in Australasia.
AB  - Australasia has a strong record in clinical trials in malignant pleural
      mesothelioma (MPM), driven by the relatively high incidence of this disease in
      the region. Two current and three proposed trials in mesothelioma in this region
      are discussed, covering the diverse clinical scenarios of diagnosis and staging,
      health-related quality of life, maintenance therapy, prediction of response and
      combined modality treatment.

PMID- 15950791
TI  - Overview on ongoing or planned clinical trials in Europe.
AB  - Malignant pleural mesothelioma (MPM) is a locally invasive malignancy, but only a
      minority of patients can benefit by surgical resection. Among chemotherapeutic
      agents only vinorelbine, edatrexate, gemcitabine and raltitrexed have
      demonstrated response rates >20%. The largest randomised trial in MPM showed an
      improved median survival with cisplatin and pemetrexed versus cisplatin alone
      from 9.3 to 12.1 months. For the present overview about 70 requests of
      information were sent to the major European centres of thoracic oncology. The
      most widespread study treatment in Europe is an 'Extended Access Program (EAP)'
      evaluating pemetrexed alone or combined with cisplatin or carboplatin with about
      1500 enrolled patients. Two other international randomized studies compare
      pemetrexed plus best supportive care (BSC) versus BSC alone, and the role of
      Ranpirnase (Onconase) in MPM. Important national trials are ongoing: in the UK
      the addressed questions were the role of radical surgery (MARS Trial), the role
      of chemotherapy (MS-01 trial) and the role of VATS on active treatment of pleural
      effusion. In Switzerland the SAKK group phase III study explores in a comparative
      way the value of hemithoracic radiotherapy after primary treatment with
      cisplatin/pemetrexed followed by surgery. In Italy, 2 phase II trials of
      neoadjuvant chemotherapy (pemetrexed plus cisplatin in Rome, pemetrexed plus
      carboplatin in Padua) followed by surgery and radiotherapy are active. With the
      important exception of UK, the most evident element is the overwhelming presence
      of pemetrexed in the ongoing and future clinical trials. Pemetrexed has
      influenced not only the clinical practice, but also the patient enrolment in
      clinical trials.

PMID- 15950792
TI  - Consensus report: pretreatment minimal staging and treatment of potentially
      resectable malignant pleural mesothelioma.

PMID- 15950793
TI  - Epidemiology of mesothelioma--a South African perspective.

PMID- 15950794
TI  - Epidemic of mesothelioma in Egypt.
AB  - Asbestos has been recognized in Egypt since a long time as ancient Egyptians were
      using it in mummification. Mesothelioma in Egypt is mainly attributed to
      environmental origin with a high incidence of women and young adults affected.
      The incidence of mesothelioma is rising in Egypt. Epidemiological data for 635
      malignant mesothelioma (MM) patients over 4 years in the third Millennium were
      collected from the National Cancer Institute (NCI), Cairo University and Abbassia
      Chest hospital. This number is more than four times the number diagnosed in the
      previous 11 years at NCI. A clinicopathological study was done for 100 malignant
      pleural mesothelioma (MPM) patients and showed that asbestos exposure and SV40
      positivity were evident in 67% and 60% of cases, respectively. The median
      survival was 14.3 months and the 1 and 2 year survival rates were 60% and 27%,
      respectively. Evaluation of p53 and pRb immunohistochemically showed that pRb
      alteration was related to poor survival. Other biological prognostic factors such
      as EGFR, HER-2, glutathione S transferase (GST) and MDR were evaluated in 50
      cases. Overexpression of EGFR was correlated with lack of clinical benefit and
      poor survival. GST potentiated the effect of EGFR on survival. The use of EGFR
      inhibitors may have a role in the treatment of MM. Asbestos in Cairo is a silent
      killer and measures toward eliminating it entirely or at least strictly
      controlling human contact with this dangerous carcinogen have to be taken in
      order to combat the coming epidemic of mesothelioma in Egypt.

PMID- 15950795
TI  - Imaging, staging and response evaluation.

PMID- 15950796
TI  - The role of PET in the surgical management of malignant pleural mesothelioma.
AB  - Current imaging modalities fail to define precisely the extent of disease in MPM
      and are inaccurate in selecting patients for treatment. Previous studies have
      shown that CT and MRI provide anatomical information that is often imprecise in
      the preoperative staging of MPM. Consequently, about 25% of patients are found to
      have unresectable tumor at the time of exploratory thoracotomy. PET is now widely
      recognized as an important staging modality in many cancers, and PET SUV is
      reported as a prognostic indicator in several malignancies. However, only a few
      previous studies have investigated the utility of FDG PET scan in MPM. From 1998
      to 2003, 65 patients with MPM underwent PET scans. Median PET SUV in the primary
      tumor was 6.6 (range, 2-23). The median follow-up for all surviving patients was
      16 months. Median survivals were 14 and 24 months for the high and low SUV
      groups, respectively. In a multivariable analysis, high SUV tumors were
      associated with a 3.3 times greater risk of death than low SUV tumors (p = 0.03).
      Mixed histology carried a 3.2 times greater risk of death than epithelial
      histology (p = 0.03). SUV of >4 and mixed histology are poor risk factors in
      malignant pleural mesothelioma. These findings suggest that FDG-PET can be used
      to stratify patients for treatment and clinical trials.

PMID- 15950797
TI  - Asbestos and mesothelioma: worldwide trends.
AB  - A correlation between national asbestos consumption and the incidence of asbestos
      disease, including mesothelioma, has been observed. Towards the end of the 20th
      century, governments in many developed countries banned or seriously restricted
      the use of asbestos. As a result, global asbestos producers have engaged in
      aggressive marketing campaigns to sell asbestos to developing countries;
      consumption of white asbestos is increasing in Asia, Latin America and the
      Commonwealth of Independent States. In most of the countries, there is little, if
      any, control on hazardous asbestos exposures from occupational, environmental and
      domestic sources. It is likely that the lethal asbestos harvest which is
      occurring in the U.S., the UK and Australia will be reproduced in the developing
      world.

PMID- 15950798
TI  - Therapy response evaluation in malignant pleural mesothelioma with integrated PET
      CT imaging.

PMID- 15950799
TI  - CT, RECIST, and malignant pleural mesothelioma.
AB  - The unique growth pattern of malignant pleural mesothelioma (MPM) presents
      challenges for clinical investigators assessing tumour response to treatment.
      Assessment of response is an important surrogate for patient benefit,
      particularly in phase II clinical trials. Neither the previous WHO criteria nor
      the more recent RECIST criteria are well suited to tumour measurement in this
      disease. This paper discusses uni-dimensional measurement of tumour response in
      pleural mesothelioma, and the development and validation of the modified RECIST
      criteria for MPM, which attempt to overcome some of the shortcomings of the
      RECIST criteria in this setting.

PMID- 15950800
TI  - Computerized analysis of mesothelioma on CT scans.
AB  - Computed tomography (CT) has become an essential tool for monitoring the
      progression of mesothelioma tumor or a patient's response to treatment. Despite
      the accepted role of CT for the evaluation of mesothelioma, however, the current
      standard practice remains the manual measurement of tumor extent on CT scans. The
      process of manual measurement acquisition is tedious and subject to
      inconsistency. We have quantitatively assessed the variability of manual
      mesothelioma measurements both in baseline CT scans and in the context of tumor
      response classification across temporally sequential scans. To facilitate the
      acquisition of mesothelioma measurements, we have developed and evaluated
      computerized methods for the assessment of mesothelioma tumor thickness on CT
      scans; we anticipate that such computer-assisted approaches will make the
      radiologic assessment of mesothelioma more efficient, thus facilitating the
      establishment of improved clinical protocols.

PMID- 15950801
TI  - Malignant pleural mesothelioma: staging systems.
AB  - Malignant pleural mesothelioma has a very specific growth pattern invading the
      pleural surfaces and neighboring structures. For this reason precise estimation
      of tumor volume and description of local extension are particularly difficult.
      Different staging systems have been introduced, and the most widely used are
      discussed. Restaging of mesothelioma after induction therapy is even more
      complicated and still controversial. The recently described, modified response
      evaluation criteria in solid tumors (RECIST) criteria are presently the most
      accurate for response evaluation.

PMID- 15950802
TI  - Molecular prognostic markers in malignant mesothelioma.
AB  - Malignant mesothelioma remains a highly lethal cancer. Recent advances in both
      surgical and medical therapy have improved survival, but the treatments remain
      toxic and selection of appropriate patients for these therapies is difficult.
      Research into the molecular pathways involved in the development of mesothelioma
      should yield information that will guide therapeutic decisions in the near
      future. In particular, expression of EGFR and VEGF receptor hold promise to alter
      standards of patient care in the next few years. Alterations in cell cycle
      control proteins such as p16, p21, and p27 also offer information on prognosis
      and represent potential targets for therapy.

PMID- 15950803
TI  - Chemotherapy for malignant mesothelioma.

PMID- 15950804
TI  - Neoadjuvant chemotherapy in malignant pleural mesothelioma.

PMID- 15950805
TI  - Induction chemotherapy, extrapleural pneumonectomy, and radiotherapy in the
      treatment of malignant pleural mesothelioma: the Memorial Sloan-Kettering
      experience.
AB  - Approximately 25% of patients with malignant pleural mesothelioma (MPM) prove
      unresectable at surgery and the median survival of stage III MPM is <12 months
      even after complete resection by extrapleural pneumonectomy. From 1939-2004, a
      series of sequential clinical trials has been performed at our institution. The
      surgical procedure has been modified and improved upon, and adjuvant hemithoracic
      radiation (RT) standardized. The evolution of our current standard of care for
      MPM is discussed. Improving chemotherapy for MPM led us to test induction
      chemotherapy followed by EPP and adjuvant RT for locally advanced MPM to assess
      feasibility. Patients with T3-4 or N2 MPM by CT and PET scans were enrolled on a
      phase II study. Induction therapy was: gemcitabine (1250 mg/m2 days 1, 8) and
      cisplatin (75 mg/m2 day 8)x2-4 cycles. Patients underwent EPP 3-5 weeks after
      induction therapy, then 54 Gy RT 4-6 weeks postop. At surgery, 8/9 had complete
      resection by EPP with no postoperative deaths. All received planned adjuvant RT.
      This combined modality approach is feasible for locally advanced MPM, and initial
      analysis suggests improved resectability. This experience supports additional
      studies of induction and multimodality therapy, especially with regimens such as
      cisplatin and pemetrexed which may be better tolerated and more effective.

PMID- 15950806
TI  - Treatment planning system evaluation for mesothelioma IMRT.
AB  - BACKGROUND AND PURPOSE: Malignant pleural mesothelioma (MPM) has been treated
      with extrapleural pneumonectomy (EPP) followed by IMRT. IMRT improved radiation
      dose distributions to the complex operative bed, and preliminary results
      suggested improved local control compared with conventional treatment planning.
      IMRT was initially developed on the Corvus treatment planning system. Other
      treatment planning systems are also IMRT-capable. Treatment plans from several
      systems were compared to determine the feasibility of using IMRT in a multi
      institution trial. PATIENTS AND METHODS: Treatment plans were generated on
      Corvus, Eclipse, and Pinnacle for a right-sided MPM after EPP using 6 MV X-rays.
      Tissue heterogeneity corrections were used in dose calculation. Plans were
      optimized such that the clinical target volume received 50 Gy in 25 fractions.
      Dose distributions to the target and normal structures were evaluated. The
      treatment time and delivery efficiency were estimated. RESULTS: Treatment plans
      could be calculated by all three planning systems without system failure. Larger
      volumes received 60Gy in Corvus plans (40%, 17% and 8% for Corvus, Pinnacle and
      Eclipse, respectively). Corvus used the most monitor units (2786 versus 1451 and
      1813 for Pinnacle and Eclipse), and treated the most segments (1050 versus 267
      and 173 for Pinnacle and Eclipse). Doses to spinal cord, lung, heart, liver, and
      contralateral kidney were acceptable for all planning systems. CONCLUSIONS: IMRT
      plans can be calculated for MPM targets by at least three commonly available
      treatment planning systems. Pinnacle- and Eclipse-based plans seem more
      efficient, and may be delivered in a shorter time than Corvus-based plans.

PMID- 15950807
TI  - Inverse planned stereotactic intensity modulated radiotherapy (IMRT) in the
      palliative treatment of malignant mesothelioma of the pleura: the Heidelberg
      experience.
AB  - Intensity modulated radiation therapy (IMRT) is a new promising treatment
      technique, which allows a more conformal application of the dose to the tumor
      volume, as compared to conventional radio-oncological approaches, while
      protecting the surrounding normal tissue more accurately. This manuscript
      presents the final results of IMRT in the treatment of unresectable pleural
      mesothelioma in Heidelberg.

PMID- 15950808
TI  - Molecular and Immunological approaches.

PMID- 15950809
TI  - Site-related expression of metastasis-associated and signaling molecules in
      malignant mesothelioma--a new model for the study of tumor biology and disease
      progression.

PMID- 15950810
TI  - Asbestos problem in India.
AB  - Primary exposure to asbestos in India can be encountered in the form of asbestos
      mining, asbestos cement industries, asbestos processing unit and during
      renovation and demolition of old asbestos cemented roof or other structures as
      well as modern electrical as well as mechanical appliances in which asbestos is
      still found. Ultimately construction workers, electricians, vehicle mechanics and
      other workers in the building trades who are exposed to asbestos inhale hundreds
      and thousands of amphiboles, which causes lung damage. It is being mined in India
      at places such as Andhra Pradesh (Pulivendla), Jharkand (Roro), Rajasthan (Ajmer,
      Bhilwara, Udaipur, Rajsamand) and the common problem faced by the locals are
      asbestosis through air and fluorosis through drinking water. The problem
      continues to be in India as well as other developing countries. Also, India
      import and re-export asbestos to other countries and workers at shipyard,
      transport of the hazardous material on road and roadside residents all are
      vulnerable to this uncommon disease. The signs and symptoms generally found with
      the workers are shortness of breath, persistent and productive cough due to
      pulmonary fibrosis can show up many years after the asbestos exposure.

PMID- 15950811
TI  - Implications of P16/CDKN2A deletion in pleural mesotheliomas.
AB  - Homozygous deletion of P16/CDKN2A is found in approximately 75% of mesotheliomas
      amd may be the most common genetic alteration in this cancer. In terms of
      diagnostic applications, its high prevalence makes it a useful marker to
      distinguish malignant mesothelial cells from benign reactive ones in pleural
      fluid cytologic preparations. In terms of prognosis, P16/CDKN2A loss is
      associated with more aggressive clinical behavior in mesotheliomas. The
      homozygous co-deletion of MTAP, encoding the enzyme methylthioadenosine
      phosphorylase, in approximately 90% of mesotheliomas with P16/CDKN2A loss has
      potential therapeutic applications because MTAP-deficient tumors may be
      responsive to inhibitors of de novo AMP synthesis. Finally, global gene
      expression profiling using Affymetrix U133A chips finds few gene expression
      correlates of P16/CDKN2A deletion in pleural mesothelioma, consistent with its
      non-transcriptional mode of direct action through regulation of cell cycle
      related kinase signaling.

PMID- 15950812
TI  - Transcriptional profiling of mesothelioma using microarrays.
AB  - Mesothelioma is an asbestos-related neoplasm of the thoracic pleura about which
      little is known and for which effective therapy is lacking. Large-scale
      transcriptional profiling using microarrays is frequently a part of studies to
      explore gene expression patterns in cancer and other diseases. In general,
      microarray based experiments can facilitate the identification of tumor molecular
      markers, provide clues relating to mechanisms carcinogenesis, as well as aid in
      the discovery of candidate targets for therapy. Relatively few studies of this
      sort have been attempted for mesothelioma, likely due to its relatively rare
      incidence and by extension the difficulty in acquiring suitable tissues for
      analysis. Microarray analysis of mesothelioma will likely lead to a better
      understanding of a highly lethal malignancy and result in the identification of
      potential therapeutic targets to ultimately affect better treatment options and
      patient clinical outcome. This mini-review will address general issues pertaining
      to all expression profiling experiments (e.g., data interpretation) and summarize
      similar studies that have been attempted for mesothelioma.

PMID- 15950813
TI  - Criteria for the safety evaluation of flavoring substances. The Expert Panel of
      the Flavor and Extract Manufacturers Association.
AB  - The current status of the GRAS evaluation program of flavoring substances
      operated by the Expert Panel of FEMA is discussed. The Panel maintains a rigorous
      rotating 10-year program of continuous review of scientific data related to the
      safety evaluation of flavoring substances. The Panel concluded a comprehensive
      review of the GRAS (GRASa) status of flavors in 1985 and began a second
      comprehensive review of the same substances and any recently GRAS materials in
      1994. This second re-evaluation program of chemical groups of flavor ingredients,
      recognized as the GRAS reaffirmation (GRASr) program, is scheduled to be
      completed in 2005. The evaluation criteria used by the Panel during the GRASr
      program reflects the significant impact of advances in biochemistry, molecular
      biology and toxicology that have allowed for a more complete understanding of the
      molecular events associated with toxicity. The interpretation of novel data on
      the relationship of dose to metabolic fate, formation of protein and DNA adducts,
      enzyme induction, and the cascade of cellular events leading to toxicity provides
      a more comprehensive basis upon which to evaluate the safety of the intake of
      flavor ingredients under conditions of intended use. The interpretation of
      genotoxicity data is evaluated in the context of other data such as in vivo
      animal metabolism and lifetime animal feeding studies that are more closely
      related to actual human experience. Data are not viewed in isolation, but
      comprise one component that is factored into the Panel's overall safety
      assessment. The convergence of different methodologies that assess intake of
      flavoring substances provides a greater degree of confidence in the estimated
      intake of flavor ingredients. When these intakes are compared to dose levels that
      in some cases result in related chemical and biological effects and the
      subsequent toxicity, it is clear that exposure to these substances through flavor
      use presents no significant human health risk.

PMID- 15950814
TI  - The FEMA GRAS assessment of phenethyl alcohol, aldehyde, acid, and related
      acetals and esters used as flavor ingredients.
AB  - This publication is the ninth in a series of safety evaluations performed by the
      Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993,
      the Panel initiated a comprehensive program to re-evaluate the safety of more
      than 1700 GRAS flavoring substances under conditions of intended use. Elements
      that are fundamental to the safety evaluation of flavor ingredients include
      exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor
      ingredients are evaluated individually and in the context of the available
      scientific information on the group of structurally related substances.
      Scientific data relevant to the safety evaluation of the use of phenethyl
      alcohol, aldehyde, acid, and related acetals and esters as flavoring ingredients
      is evaluated. The group of phenethylalcohol, aldehyde, acid, and related acetals
      and esters was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting
      properties as flavoring substances in food, their rapid absorption, metabolic
      detoxication, and excretion in humans and other animals, their low level of
      flavor use, the wide margins of safety between the conservative estimates of
      intake and the no-observed-adverse effect levels determined from subchronic and
      chronic studies and the lack of significant genotoxic and mutagenic potential.
      This evidence of safety is supported by the fact that the intake of phenethyl
      alcohol, aldehyde, acid, and related acetals and esters as natural components of
      traditional foods is greater than their intake as intentionally added flavoring
      substances.

PMID- 15950815
TI  - The FEMA GRAS assessment of benzyl derivatives used as flavor ingredients.
AB  - This publication is the eighth in a series of safety evaluations performed by the
      Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993,
      the panel initiated a comprehensive program to re-evaluate the safety of more
      than 1700 GRAS flavoring substances under conditions of intended use. Elements
      that are fundamental to the safety evaluation of flavor ingredients include
      exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor
      ingredients are evaluated individually and in the context of the available
      scientific information on the group of structurally related substances.
      Scientific data relevant to the safety evaluation of the use of benzyl
      derivatives as flavoring ingredients is evaluated. The group of benzyl
      derivatives was reaffirmed as GRAS (GRASr) based, in part, on their self-limiting
      properties as flavoring substances in food; their rapid absorption, metabolic
      detoxication, and excretion in humans and other animals, their low level of
      flavor use, the wide margins of safety between the conservative estimates of
      intake and the no-observed-adverse effect levels determined from subchronic and
      chronic studies and the lack of significant genotoxic and mutagenic potential.
      This evidence of safety is supported by the fact that the intake of benzyl
      derivatives as natural components of traditional foods is greater than their
      intake as intentionally added flavoring substances.

PMID- 15950816
TI  - The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives
      used as flavor ingredients.
AB  - This publication is the ninth in a series of safety evaluations performed by the
      Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993,
      the Panel initiated a comprehensive program to re-evaluate the safety of more
      than 1700 GRAS flavoring substances under conditions of intended use. Elements
      that are fundamental to the safety evaluation of flavor ingredients include
      exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor
      ingredients are evaluated individually and in the context of the available
      scientific information on the group of structurally related substances.
      Scientific data relevant to the safety evaluation of the use of hydroxy- and
      alkoxy-substituted benzyl derivatives as flavoring ingredients is evaluated. The
      group of hydroxy- and alkoxy-benzyl derivatives was reaffirmed as GRAS (GRASr)
      based, in part, on their self-limiting properties as flavoring substances in
      food; their rapid absorption, metabolic detoxication, and excretion in humans and
      other animals; their low level of flavor use; the wide margins of safety between
      the conservative estimates of intake and the no-observed-adverse effect levels
      determined from subchronic and chronic studies and the lack of significant
      genotoxic and mutagenic potential. This evidence of safety is supported by the
      fact that the intake of hydroxy- and alkoxy-substituted benzyl derivatives as
      natural components of traditional foods is greater than their intake as
      intentionally added flavoring substances.

PMID- 15950817
TI  - Effects of conjugated linoleic acid on long term feeding in Fischer 344 rats.
AB  - Weanling male Fischer 344 rats were fed either control or diet containing 1% CLA
      for 18 months. Weight gain and survival rate were not different between
      treatments, but CLA-fed animals ate slightly less food. CLA feeding did not
      significantly reduce body fat compared to that of control. Clinical chemistry and
      hematology analyses were performed on blood samples at week 69-72. CLA had no
      effects except on blood glucose, which was reduced in CLA-fed animals compared to
      control. All animals had chronic renal failure at the end of the study; however,
      CLA decreased the amount of protein in urine at week 70 of feeding. Necropsy and
      histo-pathology results indicated that there was no difference between treatment
      groups. Although this study used a limited number of animals and a single dose of
      CLA, our results suggest that long term CLA feeding did not cause any adverse
      effects in rats.

PMID- 15950818
TI  - Airway inflammatory and immunological events in a rat model exposed to toluene
      diisocyanate.
AB  - To investigate the inflammatory and immunological events in the airway induced by
      a short period of repeated exposure to toluene diisocyanate (TDI), an animal
      model was established, which resembled the industrial field exposure. After whole
      body exposure of Wistar rats to 0.38 and 1.20 ppm TDI vapor 4h a day for five
      consecutive days in a glass chamber, bronchoalveolar lavage (BAL) was performed.
      BAL fluid cellular and cytokine contents were then determined. Histopathological
      examinations were also carried out on the lungs. The TDI vapor exposure resulted
      in airway symptoms similar to those in occupational asthma. BAL fluid cellular
      analysis and lung histopathological examination revealed that inflammatory
      response was characterized by marked eosinophil infiltration of the airways. The
      cytokine assay revealed significant production of IL-4 in the airways of the TDI
      exposed rats as compared to the control rats. These findings indicated that a
      short period of repeated exposure to TDI vapor may cause respiratory
      hypersensitivity in which airway inflammatory and immunological events
      represented by eosinophil infiltration and Th2 cytokines may play an important
      role. Also, this animal model may be suitable for exploring the mechanism
      underlying TDI-induced occupational asthma.

PMID- 15950819
TI  - Four weeks of oral isotretinoin treatment causes few signs of general toxicity in
      male and female Sprague-Dawley rats.
AB  - Despite widespread use of isotretinoin for its anti-acne effects and its current
      evaluation in clinical trials as a cancer treatment, little is known about its
      general toxicity in adult nonpregnant animals, particularly after oral
      administration which mimics the human route. Here, adult male and female Sprague
      Dawley rats were gavaged daily with 0 (soy oil), 7.5, or 15 mg/kg isotretinoin
      for 28 days during which time body weight, food/water intake, and estrous phase
      were measured. At sacrifice, organ weights were collected and concentrations of
      dopamine (DA), serotonin and metabolites were measured in frontal cortex,
      striatum, hippocampus, and diencephalon. Food intake was mildly decreased in both
      treated groups (approximately 15% in males and 7% in females); however, body
      weight and water consumption were unaffected. The estrous cycle appeared slightly
      affected (i.e., lengthened by 15 mg/kg, and both treated groups appeared to have
      less time in diestrus and more time in estrus). Kidney/body weight ratio was
      decreased by 7.5 and 15 mg/kg isotretinoin and spleen/body weight ratio was
      increased in the 7.5 mg/kg group. Males of the 7.5 mg/kg group exhibited
      significantly higher gonad/body weight ratios than did same-sex controls.
      Concentrations of monoamine and metabolites in the frontal cortex and
      diencephalon were unaffected. Nor were striatal DA and DOPAC concentrations
      affected; however, there were isolated effects on striatal HVA and 5-HIAA.
      Hippocampal DA concentrations were marginally increased. These data indicate mild
      effects resulting from oral isotretinoin treatment at doses which likely produce
      serum levels within the range of humans.

PMID- 15950820
TI  - On the thermal stability of the two dimeric forms of ribonuclease A.
AB  - The thermal stability of the two dimers of RNase A with N- or C-terminal swapped
      ends is investigated by means of dissociation kinetics, differential scanning
      calorimetry, and circular dichroism measurements. The data indicate that the
      dimer characterized by the swapping of the N-terminal alpha-helices is less prone
      to monomerize when compared to the dimer characterized by the swapping of the C
      terminal beta-strands. This finding is correlated to the structural features of
      the so-called open interface of the dimeric forms.

PMID- 15950822
TI  - On the origin of affinity--specificity negative correlation in DNA--probe
      interactions.
AB  - Affinity (the fastness) and specificity (the correctness) are the two important
      factors that decide the efficiency of a nucleic acid probe to target its specific
      site on a DNA lattice. DNA-probe interactions differ from protein-ligand
      interactions in a way that here the specificity and the affinity of the
      interactions correlate negatively with each other. We present a simple
      phenomenological theory to explain the negative correlation between the
      specificity and the affinity of the probe towards its target site on the template
      DNA under solution conditions. We show that a simple random jump model can
      explain this fact and we also predict that the negative correlation between the
      affinity and specificity diminishes as the temperature increases or the viscosity
      of the medium decreases. Moreover, the length of target DNA and the distance
      between the initial position of the probe on the template DNA lattice and the
      target site increases the magnitude of affinity-specificity negative correlation.
      These results are consistent with experimental observations. Finally we propose
      practical strategies to coherently improve the specificity and the affinity with
      respect to important molecular biological techniques such as PCR and Southern
      blotting.

PMID- 15950821
TI  - Unfolding mechanism of a hyperthermophilic protein O(6)-methylguanine-DNA
      methyltransferase.
AB  - Unfolding intermediates have been found only rarely in earlier studies, and how a
      protein unfolds is therefore poorly understood. In this paper, we show
      experimental evidence for multiple pathways and multiple intermediates during
      unfolding reaction of O(6)-methylguanine-DNA methyltransferase from
      hyperthermophile Thermococcus kodakaraensis (Tk-MGMT). The unfolding profiles
      monitored by far-UV CD and tryptophan fluorescence were both biphasic, and
      unfolding monitored by fluorescence was faster than that monitored by CD. GdnHCl
      induced titration curves indicate that the intermediates with significant alpha
      helical structure accumulate during unfolding. Dependence of kinetic phases on
      initial GdnHCl concentrations and cysteine reactivity of Tk-MGMT were
      investigated, suggesting that the heterogeneity of native conformations and
      parallel unfolding pathways.

PMID- 15950823
TI  - Speciation of phytate ion in aqueous solution. Dimethyltin(IV) interactions in
      NaCl(aq) at different ionic strengths.
AB  - As the introduction of a systematic study on the sequestering ability of phytate
      (Phy) towards heavy metal and organometal cations, this paper describes the
      results of an investigation (at t=25 degrees C by potentiometry, ISE-H(+) glass
      electrode) of its interactions with dimethyltin(IV) cation [(CH(3))(2)Sn(2+),
      DMT] in NaCl aqueous solutions at different ionic strengths (0.1< or =I (mol L(
      1))< or =1), in the pH range 2.5< or =pH< or =8.5 and considering metal to ligand
      ratios 1:1< or =DMT:Phy< or =4:1. We observed the formation of 18
      DMT(i)H(j)Phy((12-2i-j)-) species: with i=1 and 0< or =j< or =7; i=2 and 0< or
      =j< or =5; i=3 and 0< or =j< or =3. Their complex formation constant values are
      fairly dependent on ionic strength and this dependence was modeled by a Debye
      Huckel type equation. The speciation of phytic acid and dimethyltin(IV) is also
      dependent on the metal to ligand ratio; the dependence of the stability of
      phytate-dimethyltin(IV) species on both the phytate protonation step and the
      number of cations bound to the ligand has been modeled and an empirical
      predictive relationship is also proposed. From the results obtained it emerged
      that phytate has very good sequestering ability towards (CH(3))(2)Sn(2+).
      Comparisons are made with other ligands, such as ethylenediamine-N,N,N',N'
      tetraacetic acid (EDTA) and phosphate.

PMID- 15950824
TI  - MULTIHYDRO and MONTEHYDRO: conformational search and Monte Carlo calculation of
      solution properties of rigid or flexible bead models.
AB  - A computer program, MULTIHYDRO, has been constructed for the calculation of
      hydrodynamic coefficients and other solution properties of multiple possible
      conformations of a bead model. With minimal additional programming to describe
      the model under study, this program interfaces efficiently with HYDRO for the
      calculation of solution properties, including hydrodynamic coefficients, radius
      of gyration, covolume, etc. A useful application is the conformation search of
      rigid macromolecules, because many possible conformations can be evaluated in a
      single run of the program. In this paper we also pay attention to the properties
      of flexible macromolecules, in the so-called Monte Carlo rigid-body
      approximation, which is virtually exact for the simpler solution properties. The
      theoretical aspects of the procedure are described, and we show how MULTIHYDRO
      can be employed for this calculation. However, for flexible molecules, a more
      general simulation scheme is importance-sampling Monte Carlo generation. We
      describe how this procedure is implemented in another computer program,
      MONTEHYDRO. Examples of the usage of these tools are provided.

PMID- 15950825
TI  - Some factors determining the PCr recovery overshoot in skeletal muscle.
AB  - It has been proposed recently that the phosphocreatine (PCr) overshoot (increase
      above the resting level) during muscle recovery after exercise is caused by a
      slow decay during this recovery of the direct activation of oxidative
      phosphorylation taking place during muscle work. In the present article the
      factors determining the appearance and size of the PCr overshoot are studied
      using the computer model of oxidative phosphorylation in intact skeletal muscle
      developed previously. It is demonstrated that the appearance and duration of this
      overshoot is positively correlated with the value of the characteristic decay
      time of the direct activation of oxidative phosphorylation. It is also shown that
      the size of PCr overshoot is increased by low resting PCr/Cr ratio (what is
      confirmed by our unpublished experimental data), by high intensity of the direct
      activation of oxidative phosphorylation, by high muscle work intensity and by low
      rate of the return of cytosolic pH to the resting value during muscle recovery.

PMID- 15950826
TI  - On the hydration heat capacity change of benzene.
AB  - The heat capacity change associated with the hydration of benzene is a large and
      positive quantity, but it is significantly smaller than that associated with the
      hydration of an alkane having the same accessible surface area of benzene, the
      corresponding alkane. This large difference merits attention and should be
      rationalized. This task is performed by means of the two-state Muller's model for
      the reorganization of H-bonds. It results that: (a) the hydration shell of both
      hydrocarbons consists of H-bonds that are enthalpically stronger but slightly
      more broken than those in bulk water; (b) the hydration shell of benzene
      consists, on average, of enthalpically slightly weaker H-bonds with respect to
      the corresponding alkane. The latter feature, due to the presence of the weak
      benzene-water H-bonds, is the physical cause of the large difference in the
      hydration heat capacity change, according to the two-state Muller's model.

PMID- 15950827
TI  - Regulation of oxidative phosphorylation in intact mammalian heart in vivo.
AB  - A dynamic computer model of oxidative phosphorylation in intact heart was
      developed by modifying the model of oxidative phosphorylation in intact skeletal
      muscle published previously. Next, this model was used for theoretical studies on
      the regulation of oxidative phosphorylation in intact heart in vivo during
      transition between different work intensities. It is shown that neither a direct
      activation of ATP usage alone nor a direct activation of both ATP usage and
      substrate dehydrogenation, including the calcium-activated tricarboxylate acid
      cycle dehydrogenases, can account for the constancy of [ADP], [PCr], [P(i)] and
      [NADH] during a significant increase in oxygen consumption and ATP turnover
      encountered in intact heart in vivo. Only a direct activation of all oxidative
      phosphorylation complexes in parallel with a stimulation of ATP usage and
      substrate dehydrogenation enabled to reproduce the experimental data concerning
      the constancy of metabolite concentrations. The molecular background of the
      differences between heart and skeletal muscle in the kinetic behaviour of the
      oxidative phosphorylation system is also discussed.

PMID- 15950828
TI  - Acid-induced denaturation and refolding of prothrombin.
AB  - Structural transitions of the blood coagulation factor prothrombin (extracted
      from goat blood) in response to reduction of pH were investigated by
      fluorescence, circular dichroism and light scattering measurements. The study
      revealed the presence of a partially unfolded state at around pH 3.5,
      characterized by marked enhancement of fluorescence from ANS bound to the
      protein, increase of bimolecular rate constant for tryptophan fluorescence
      quenching and a sharp peak in the light scattering intensity. Further lowering of
      the pH caused reversal of the trend of variation of these parameters, suggesting
      that prothrombin folds back to a compact state containing native-like secondary
      structural elements. The refolded state at low pH (<pH 3) fits the description of
      the A-state, the end-point of acid-induced denaturation process of several other
      monomeric proteins, and is a possible candidate for the class of folding
      intermediates known as molten globules.

PMID- 15950829
TI  - The nop gene from Phanerochaete chrysosporium encodes a peroxidase with novel
      structural features.
AB  - Inspection of the genome of the ligninolytic basidiomycete Phanerochaete
      chrysosporium revealed an unusual peroxidase_like sequence. The corresponding
      full length cDNA was sequenced and an archetypal secretion signal predicted. The
      deduced mature protein (NoP, novel peroxidase) contains 295 aa residues and is
      therefore considerably shorter than other Class II (fungal) peroxidases, such as
      lignin peroxidases and manganese peroxidases. Comparative modeling of NoP was
      conducted using the crystal structures of Coprinus cinereus and Arthromyces
      ramosus peroxidases as templates. The model was validated by molecular dynamics
      and showed several novel structural features. In particular, NoP has only three
      disulfide bridges and tryptophan replaces the distal phenylalanine within the
      heme pocket.

PMID- 15950830
TI  - Commentary on enhancing clinician communication skills in a large healthcare
      organisation.

PMID- 15950831
TI  - Enhancing clinician communication skills in a large healthcare organization: a
      longitudinal case study.
AB  - OBJECTIVE: This article describes the approach taken over the past 16 years by
      one large healthcare organization, Kaiser Permanente (KP), to enhance the
      clinical communication and relationship skills of their clinicians. METHODS: The
      centerpiece of KP's approach has been the creation and dissemination of a
      unifying clinician-patient communication (CPC) framework for teaching and
      research called the Four Habits Model. RESULTS: The Model has served as the
      foundation for a diverse array of KP programs. Sustained improvement in patient
      satisfaction scores has been demonstrated. Clinician-patient communication
      training has become a well-established component of professional development in
      KP. DISCUSSION: Enhancing clinicians' communication with patients is a complex
      task requiring planning and organizational commitment. Factors that have
      contributed to the success and lessons learned from incorporating clinician
      communication skills across the organization are described. CONCLUSION: The KP
      experience attests to the feasibility of bringing the vital skills of effective
      communication to large numbers of busy clinicians. PRACTICE IMPLICATIONS:
      Healthcare practices wishing to enhance clinician-patient communication skills
      should consider using a consistent teaching model, ensuring strong sponsorship
      from leaders, and emphasizing clinician satisfaction in the design of programs.

PMID- 15950832
TI  - Reduction in uptake of PSA tests following decision aids: systematic review of
      current aids and their evaluations.
AB  - A man's decision to have a prostate-specific antigen (PSA) test should be an
      informed one. We undertook a systematic review to identify and appraise PSA
      decision aids and evaluations. We searched 15 electronic databases and hand
      searched key journals. We also contacted key authors and organisations. All
      decision aids and evaluations that discussed PSA were included, with meta
      analyses performed on two outcomes from the evaluations: PSA testing and patient
      knowledge of PSA and related issues. Seven decision aids and 11 evaluations were
      included. The meta-analysis showed a significantly reduced probability in PSA
      testing after a decision aid: -3.5% (95% confidence interval: 0.0 to 7.2%; P =
      0.050). There were significant improvements in knowledge within 2 weeks after a
      decision aid: 19.5% (95% confidence interval: 14.2 to 24.8%; P < 0.001). The
      effect on knowledge was less pronounced within 12-18 months after a decision aid:
      3.4% (95% confidence interval: -0.7 to 7.4%; P = 0.10). PSA decision aids improve
      knowledge about PSA testing, at least in the short term. Men given these decision
      aids seem to be less likely to have the PSA test.

PMID- 15950833
TI  - Effect of behavioral management on quality of life in mild heart failure: a
      randomized controlled trial.
AB  - There has been a lack of research regarding nonpharmacologic interventions in
      heart failure. The objective was to determine the effect of behavioral management
      on health related quality of life (HRQL) in patients with heart failure.
      Participants (N = 116) were randomly assigned to one of two groups: usual care
      for heart failure (n = 58) and the 15-week behavioral management program (n =
      58). Outcomes included exercise performance (6-min walk), physical and mental
      functioning (SF-36), general health perceptions (SF-36), and disease specific
      HRQL (Minnesota Living with Heart Failure Questionnaire-MLHF). Outcomes were
      assessed at baseline, 4, 10 and 16 months. Participants were mostly male (95%)
      and Caucasian (75%), with a mean age of 67 years (S.D. = 10). Intervention
      patients showed significantly improved self-reported disease specific HRQL (MLHF
      physical dimension scores) over time compared to control patients. There were no
      group differences in exercise performance, physical functioning, mental
      functioning or general health perceptions.

PMID- 15950834
TI  - Ethnicity and prenatal depression: women's experiences and perspectives on
      communicating about their emotions and feelings during pregnancy.
AB  - The purpose of the study was to examine the relationship between ethnicity, the
      presence of moderate to severe symptoms of depression, and communication about
      emotions and feelings during prenatal visits. The purpose was also to describe
      women's perceptions of the barriers to communicating with providers, family, and
      friends about their emotions or feelings and how to overcome these barriers.
      Seventy-three women were recruited and interviewed by a bilingual research
      assistant between June and September 2002 after a prenatal visit occurring
      between 12- and 32-week gestation. Nineteen percent of women screened as having
      moderate to severe symptoms of depression. Quality of social relationships had a
      significant negative relationship with whether women had moderate to severe
      symptoms of depression. Almost 29% of women reported discussing their emotions or
      feelings with their providers and this did not differ significantly by ethnicity.
      Women who discussed their emotions or feelings with their providers did have
      significantly higher scores on the Beck Depression Inventory-II (BDI-II) than
      those who did not. Thirty-four percent of women stated that there were barriers
      to expectant or new mothers communicating with their providers. Women who felt
      that there were barriers to expectant or new mothers discussing their emotions
      with their providers did have significantly higher BDI-II scores than those women
      who did not. Thirty-seven percent of women believed that there were barriers to
      expectant or new mothers communicating with their family about their emotions.
      Women felt that providers and families could try to develop trust with them and
      try to make them feel more comfortable discussing their feelings.

PMID- 15950835
TI  - Assessment of a therapeutic education programme for asthma patients: "un souffle
      nouveau".
AB  - The aim of this study was to evaluate the impact of a new patient education
      programme on adults with asthma. This self-management programme included an
      individual assessment of patient's needs and two educational group sessions.
      Teaching methods and session content are described as well as caregivers training
      programme. The training sessions included a written asthma action plan based on
      symptoms and personal peak expiratory flow. Patients (n = 238) aged from 18 to 60
      years were allocated to the intervention (group A) or control group (group B).
      Patients filled during 1 year a daily diary and questionnaire and they were
      administered telephone interviews. 127 patients were included in the treatment
      program and 111 in the control group. There was a significant improvement in the
      educated group with regard to symptoms free days (P = 0.03), number of awakenings
      (P = 0.04), consumption of corticosteroids (P = 0.03), consumption of beta2
      agonists (P = 0.03), and quality of life score (P = 0.01). In conclusion, this
      study validates a specific educational approach named "un souffle nouveau".

PMID- 15950836
TI  - Effect of educational programs on asthma control and quality of life in adult
      asthma patients.
AB  - This study investigated the effectiveness of different educational programs in
      obtaining better asthma control and asthma-related quality of life (QoL). In 60
      adult patients with moderate persistent asthma we tested the benefit of
      individual verbal instructions (IVI), written information ("asthma booklet", B),
      and integrated asthma classes ("asthma school", AS). At the enrollment and at the
      end of the study, all participants completed the questionnaires regarding their
      asthma-related knowledge (ArK) and QoL. During the 12-week period all patients
      recorded their asthma symptoms, morning and evening peek expiratory flow rates
      (PEFR), and the use of rescue medication. AS and IVI groups showed a
      significantly greater improvement in QoL than the B group. AS group obtained the
      highest ArK but no difference in the level of improvement among the groups has
      been documented. The improved average asthma symptom score and decreased
      utilization of the rescue medication were documented in all groups without
      significant differences among them. We also found significant improvements in
      both morning and evening PEFR in IVI group as well as in the morning PEFR in AS
      group. We conclude that among tested educational interventions the AS caused the
      best improvement in QoL while IVI produced the best overall response in both
      parameters of the asthma control and QoL.

PMID- 15950837
TI  - The impact of pain on psychological well-being in rheumatoid arthritis: the
      mediating effects of self-esteem and adjustment to disease.
AB  - The aim of this study was to determine whether self-esteem and adjustment to
      disease can mediate the association between pain and psychological well-being in
      patients with Rheumatoid Arthritis (RA). Coefficients of correlation, multiple
      linear regressions and Structural Equation Model (SEM) were employed in order to
      examine the direct and indirect relationships between pain, self-esteem,
      adjustment to disease and psychological well-being in a sample of 160 recently
      diagnosed RA-patients. The outcomes of the analyses indicate that self-esteem and
      adjustment to disease are important links between pain and psychological well
      being. Moreover, the results suggest the increasing importance of personality
      variables in mediating the relationship between pain and psychological well-being
      as the disease advances. The findings provide evidence for considerations that
      psychosocial interventions, focused on increasing the self-esteem and improving
      the adjustment to disease, may reduce the impact of pain on patients'
      psychological well-being and quality of life in general.

PMID- 15950838
TI  - Medicine labels incorporating pictograms: do they influence understanding and
      adherence?
AB  - The objective was to determine the influence of medicine labels incorporating
      pictograms on the understanding of instructions and on adherence. Eighty-seven
      Xhosa participants attending an outpatient clinic who had been prescribed a short
      course of antibiotics were randomly allocated to either a control group (41
      participants given text-only labels), or an experimental group (46 participants
      given text + pictogram labels). All participants had a maximum of 10 years of
      formal schooling. Follow-up home visits were conducted after 3-5 days to assess
      understanding of instructions and to evaluate adherence. A high adherence of
      greater than 90% was found for 54% of the experimental group, compared with only
      2% of the control group. Average percentages for understanding in the control and
      experimental groups were 70 and 95%, respectively, and average adherence was 72
      and 90%, respectively. The presence of pictograms was found to contribute
      positively to both understanding of instructions and adherence.

PMID- 15950839
TI  - Associations of social support and sex life--the HeSSup Study.
AB  - The present study characterized the associations of three sex life issues
      (importance of, satisfaction with, and ease in talking about sex life) with
      social support and reciprocity. We utilised survey data of working-aged men and
      women (n = 21,101) from the population-based random sample of the Health and
      Social Support (HeSSup) Study (40% response). The respondents with abundant
      social support considered sex life important, were satisfied with it, and found
      it easy to talk about sex life more often than those with less social support.
      Social support in sex life offered by one's own spouse/partner was important
      particularly to women, not available from the other sources to the same extent.
      Friends functioned as significant positive sources of support in sex life
      particularly among women, but relatives did not. Mutual reciprocity was
      associated with favourable perceptions of sex life. Persons lacking established
      primary social support should have easy access to services.

PMID- 15950840
TI  - Development of a questionnaire to measure heart disease risk knowledge in people
      with diabetes: the Heart Disease Fact Questionnaire.
AB  - This paper describes a paper and pencil questionnaire that measures heart disease
      risk knowledge in people with diabetes. The Heart Disease Fact Questionnaire
      (HDFQ) is a 25-item questionnaire that was developed to tap into respondents'
      knowledge of major risk factors for the development of CHD. Approximately half of
      these items specifically address diabetes-related CHD risk factors. Based on
      extensive pilot data, the current study analyzed responses from 524 people with
      diabetes to assess the psychometric properties. The HDFQ is readable to an
      average 13-year old and imposes little burden. It shows good content and face
      validity. It demonstrates adequate internal consistency, with Kuder-Richardson-20
      formula = 0.77 and good item-total correlations. Item analysis showed a desirable
      range in P-values. In discriminant function analyses, HDFQ scores differentiated
      respondents by knowledge of their own cardiovascular health, use of lipid
      lowering medications, health insurance status, and educational attainment, thus
      indicating good criterion related validity. This measure of heart disease risk
      knowledge is brief, understandable to respondents, and easy to administer and
      score. Its potential for use in research and practice is discussed. Future
      research should establish norms as well as investigate its test-retest
      reliability and predictive validity.

PMID- 15950841
TI  - Education for men with solvent-induced chronic toxic encephalopathy and their
      spouses.
AB  - In this study an education, and a series of group sessions for patients with
      solvent-induced chronic toxic encephalopathy (TE) and their spouses are
      evaluated. Thirty-eight patients and 21 family members participated in a 1-day
      education scheduled with short lectures on the clinical examination of chronic
      toxic encephalopathy and the prognosis. A specialist in occupational medicine, a
      psychologist and a social worker gave the lectures. Small discussion groups were
      also arranged. Of the participants from the educational days, 16 TE patients and
      14 wives attended a 10-week counselling and coping improvement program with
      separate group sessions once a week, for patients and spouses. Questionnaires
      were used to assess symptoms, social network, mastery and family climate, and the
      participants' satisfaction with the education and the group sessions. The
      majority of the participants experienced the 1-day information as useful and
      relevant. The 10-week group sessions were rated as meaningful and the design,
      number, duration and frequency of the sessions equally good. Self-reported
      symptoms, social network and mastery were measured before the group sessions, and
      3 and 9 months after breaking up the group sessions. In most measurements, there
      were no statistically significant differences between the three points in time.
      However, the wives improved more than did the patients but the effect was not
      lasting the whole follow-up period. Considering the patients' dependence on their
      wives, it might be most important that the wives experienced some relief from
      their own symptoms.

PMID- 15950842
TI  - How do cancer patients choose their coping strategies? A qualitative study.

PMID- 15950843
TI  - The impact of changes in practice in organ procurement on the satisfaction of
      donor relatives.
AB  - In the past decade several interventions have been undertaken to close the gap
      between demand and supply of donor organs. Family refusal is an important factor
      contributing to the shortage of donor organs. The importance of the quality of
      communication between staff and relatives has been underestimated. It is in the
      frontline of practice where decisions are made and behaviour of staff is
      critical. The current study, undertaken to explore if any changes had occurred in
      the behaviour of professionals involved in organ donation, took satisfaction
      ratings of relatives of donors in 1995, 1998 and 2001 as outcome measures. Our
      results show that relatives in 2001 are significantly more satisfied than those
      in 1995 and 1998 about staff behaviour. Changes all relate to specific
      interactions between key professionals and relatives. Results indicate that
      future interventions may be more effective if macro-oriented and regulatory
      policies are combined with competence-based educational programmes.

PMID- 15950844
TI  - Sequence analysis: responsiveness of doctors to patient cues during family
      planning consultations in Mexico.

PMID- 15950845
TI  - Seldinger approach to the difficult airway.

PMID- 15950846
TI  - Cardiac index measurements during rapid preload changes: a comparison of
      pulmonary artery thermodilution with arterial pulse contour analysis.
AB  - STUDY OBJECTIVE: To compare cardiac index (CI) values obtained by pulmonary
      artery thermodilution (CIPA), arterial thermodilution (CITD), and arterial pulse
      contour analysis (CIPC) during rapid fluid administration, as accurate and rapid
      detection of CI changes is critical during acute preload changes for guiding
      volume and vasopressor therapy in critically ill patients, and the accuracy of
      CIPC during acute changes in loading condition is currently unknown. DESIGN:
      Prospective clinical study. SETTING: Cardiac surgical intensive care unit of a
      university hospital. PATIENTS: Seventeen American Society of Anesthesiologists
      (ASA) physical status II and III patients, aged 32 to 76 years, with normal left
      ventricular function during the early postoperative period after elective
      coronary artery bypass graft surgery. MEASUREMENTS: After baseline determinations
      of CIPA, CIPC, and CITD were made, fluid loading was performed using 10 mL times
      body mass index of hydroxyethyl starch 6%. CIPA, CIPC, and CITD were determined,
      and changes in CI (DeltaCI) were calculated. Fluid load was repeated until no
      increase in stroke volume index (DeltaSVI <10%) was achieved. MAIN RESULTS:
      Regression analysis between CIPA/CIPC, CIPA/CITD, and CIPC/CITD revealed r2 =
      0.92, r2 = 0.92, and r2 = 0.98. Regression analysis between DeltaCIPA/DeltaCIPC,
      DeltaCIPA/DeltaCITD, and DeltaCIPC/DeltaCITD revealed r2 = 0.57, r2 = 0.67, and
      r2 = 0.74, respectively. Bland-Altman analysis was used to determine accuracy and
      precision of the 3 methods compared. The mean differences (m) and SD between
      DeltaCIPA/DeltaCIPC, DeltaCIPA/DeltaCITD, and DeltaCIPC/DeltaCITD resulted in m =
      -1.01%, SD = 6.51%; m = -0.83%, SD = 5.80%; and m = -0.33%, SD = 4.65%,
      respectively. CONCLUSION: Compared with pulmonary artery thermodilution, arterial
      pulse contour analysis reflects relative changes in CI during rapid changes of
      preload with clinically acceptable accuracy.

PMID- 15950847
TI  - Effect of intravenous hydroxyethyl starch on the accuracy of measuring hemoglobin
      concentration.
AB  - STUDY OBJECTIVE: To determine if intravenous hydroxyethylstarch (HES) affects the
      accuracy of hemoglobin (Hb) measurements, as artificial colloids are known to
      increase red blood cell sedimentation rates. DESIGN: Prospective, randomized
      study. SETTING: Tertiary-care academic medical institution. PATIENTS AND
      INTERVENTIONS: We randomized 40 surgical American Society of Anesthesiologists
      (ASA) physical status I and II patients undergoing preoperative autologous blood
      donation before elective orthopedic surgery. Patients were randomized to receive
      volume replacement with 500 mL of 6% HES 200,000/0.5 or 500 mL of electrolyte
      solution. Measurements of Hb concentration and leukocyte count were performed
      using an analyzer with a suction needle sampling from the bottom of the test
      tube. Measurements were performed after mixing and repeated after a 10-minute
      period of upright positioning of the tube (at rest). MAIN RESULTS: In the study
      group that received HES, Hb levels were increased above baseline after resting
      (mean increase to 151% of baseline values, P < .01), whereas the leukocyte count
      was decreased (mean decrease to 39% of baseline values, P < .01). No difference
      between baseline and resting measurements were observed in patients who received
      intravenous crystalloids. In addition, we repeatedly measured the Hb
      concentration in an unstirred tube with and without the addition of HES. In blood
      samples containing HES, the Hb concentration was increased above baseline after
      2.5 minutes of resting, compared with 30 minutes without HES addition (P < .05).
      CONCLUSIONS: Mixing of test tube contents before sampling is critical for
      accurate measurement of the Hb concentration in the blood of patients who
      received intravenous HES.

PMID- 15950848
TI  - Esophageal intubation with indirect clinical tests during emergency tracheal
      intubation: a report on patient morbidity.
AB  - STUDY OBJECTIVE: To determine the consequences of esophageal intubation (EI) when
      using standard indirect clinical tests to detect endotracheal tube (ETT)
      placement in the emergency setting outside the operating room (OR). DESIGN: An
      observationally based review of a quality improvement database for emergency
      intubation outside the OR. SETTING: Seven hundred sixty-five-bed tertiary care,
      level I trauma center in central Connecticut. PATIENTS: Critically ill patients
      (n = 2377) experiencing cardiopulmonary, traumatic, septic, metabolic, or
      neurologic-based deterioration and requiring emergency airway management.
      Tracheal intubation of patients with cardiopulmonary resuscitation and chest
      compressions were excluded. MEASUREMENTS: A quality improvement emergency
      intubation database from 1990 to 2001 was reviewed to determine the incidence of
      EI and its associated complications (mild and severe hypoxemia, regurgitation,
      aspiration, hemodynamic alteration, cardiac dysrhythmias, and cardiac arrest)
      when ETT position is determined by standard indirect clinical tests without the
      benefit of ETT-verifying devices. RESULTS: Patients who had EI, in contrast to
      those who did not, had significant rates of hypoxemia (64.7% vs 13.1%; P < .001)
      and severe hypoxemia (Spo2 < 70%) (25% vs 4.4%; P < .001). The rate of
      regurgitation (24.7% vs 2.4%) and aspiration (12.8% vs 0.8%) also differed
      significantly (P < .001). The overall incidence of bradycardia, typically hypoxia
      driven, was more common (14-fold) after EI (21.3% vs 1.5%), as was new onset
      cardiac dysrhythmia (6-fold increase, 23.4% vs 4.1%) and cardiac arrest (14-fold
      increase, 10.2% vs 0.7%), all P < .001. CONCLUSION: These data suggest that EI
      during emergency intubation, when detected by standard indirect clinical tests
      based on physical examination, contributes significantly to mild and severe
      hypoxemia, regurgitation, aspiration, bradycardia, cardiac dysrhythmias, and
      cardiac arrest. Pursuing methods to hasten the detection of EI in the emergency
      setting appear warranted.

PMID- 15950849
TI  - The number of injections does not influence absorption of bupivacaine after
      cervical plexus block for carotid endarterectomy.
AB  - STUDY OBJECTIVE: To investigate the efficacy and kinetics of bupivacaine when
      used for deep cervical plexus block (CPB), using either a single-injection or
      multiple-injections technique. DESIGN: Prospective, randomized, double-blind
      study. SETTING: Operating room of a university hospital. PATIENTS: Twenty-four
      adult patients (16 men, 8 women) scheduled for carotid endarterectomy.
      INTERVENTIONS: Patients were randomly assigned to receive CPB either by a single
      injection or after 3 injections. Patients in the multiple-injections group
      received a total dose of 15 mL of 0.5% bupivacaine (5 mL each deposited at C2,
      C3, and C4 over 2 minutes). Patients in the single-injection group received a
      single 15-mL injection of 0.5% bupivacaine. After the deep CPB, a superficial CPB
      was performed with 20 mL of 0.5% bupivacaine in all patients. MEASUREMENTS: An
      anesthesiologist and a surgeon graded the success of the block. Arterial plasma
      concentrations of bupivacaine were measured using liquid chromatography-mass
      spectroscopy. MAIN RESULTS: No significant differences were seen between the 2
      groups with respect to the mean peak concentration of bupivacaine (single
      injection 2314 +/- 1385 ng/mL vs multiple injections 2255 +/- 1105 ng/mL) or time
      to reach the maximal concentration (time to maximum concentration [single
      injection 12.1 +/- 7.2 minutes vs multiple injections 12.5 +/- 3.9 minutes]).
      Furthermore, there were no significant differences in mean block scores between
      the single-injection and the multiple-injections groups, evaluated either by the
      anesthesiologists or the surgeon. CONCLUSIONS: The results of this study showed
      that the absorption of bupivacaine is independent of the number of injections
      after CPB, and that anesthesia for carotid endarterectomy may be accomplished
      successfully using either technique.

PMID- 15950850
TI  - Tracheal width and left double-lumen tube size: a formula to estimate left
      bronchial width.
AB  - STUDY OBJECTIVE: To determine which patient parameters best predict left
      bronchial width (LBW) when selecting the correct size double-lumen tube (DLT). If
      LBW is known, a DLT that will fit that bronchus can be chosen. DESIGN:
      Prospective study. SETTING: University medical center. PATIENTS: Three hundred
      twenty-one consecutive patients scheduled for thoracic surgery and for whom there
      was a chest radiograph and for whom tracheal width (TW) and LBW could be
      measured. MEASUREMENTS: Tracheal width and LBW were directly measured from the
      chest radiograph. Patient demographic data were recorded and then analyzed to see
      which factor(s) best predicted LBW. Parameters often used for DLT selection (age,
      sex, height, and weight) as well as TW were compared by univariate and
      multivariate statistical analysis to see which factor(s) most accurately
      predicted LBW. MAIN RESULTS: There were weak but significant correlations between
      age and height and LBW in men, and height and LBW in women. Multivariate
      statistical analysis showed that, for both men and women, TW was the best
      predictor of LBW. Sex, height, and weight did not improve predictability over TW
      alone. The equation that best predicts LBW for both sexes is: LBWmm =
      (0.50)(TWmm) + 3.7 mm. This model explains 46% of the variance in LBW. As
      structures measured from a chest radiograph are magnified by 10%, the formula to
      predict LBW, which normalizes for this magnification factor, is: LBWmm =
      (0.45)(TWmm(CXR)) + 3.3 mm. CONCLUSIONS: Direct airway measurement is the most
      accurate way to select an appropriate DLT. However, when direct measurement of
      LBW cannot be performed, estimating LBW from TW is a better predictor of LBW than
      either sex, height, or weight.

PMID- 15950851
TI  - Morphine sparing with droperidol in patient-controlled analgesia.
AB  - STUDY OBJECTIVE: To determine if droperidol has a morphine-sparing effect when
      coadministered with morphine via patient-controlled analgesia (PCA) for
      postoperative pain management. DESIGN: A randomized, double-blind clinical study.
      SETTING: Department of Anesthesiology, Kaohsiung Veterans General Hospital,
      Taiwan. PATIENTS: One hundred seventy-nine American Society of Anesthesiologists
      physical status 1 and 2 female patients undergoing abdominal hysterectomy.
      INTERVENTIONS: At the end of surgery, patients in the droperidol group received
      PCA, with the device programmed to deliver a bolus dose of 1 mg morphine and 50
      mug droperidol on demand. Patients in the control group received 1 mg morphine on
      demand. For both groups, PCA lockout was 5 minutes between boluses, with a 4-hour
      morphine limit of 30 mg. MEASUREMENTS AND MAIN RESULTS: Pain intensity at rest or
      on movement and relative sedation score were evaluated and recorded at 6, 12, 24,
      48, and 72 hours after surgery. Related side effects were also evaluated and
      recorded on postoperative days 1, 2, and 3. Morphine use was significantly lower
      for the droperidol group than the control group during the postoperative 72-hour
      period (33.9 +/- 9.8 and 54.9 +/- 12.1 mg, respectively), with significantly
      decreased pain intensity levels for the former relative to the latter at 48 hours
      (pain intensity on movement: 3.9 +/- 1.2 vs 4.3 +/- 0.9, respectively; P = .049)
      and 72 hours (pain intensity on movement: 3.0 +/- 1.1 vs 3.6 +/- 0.5,
      respectively; P = .003; pain intensity at rest: 1.3 +/- 1.0 vs 1.6 +/- 0.7,
      respectively; P = .033) subsequent to surgery. Control subjects demonstrated a
      greater frequency of postoperative nausea and vomiting than did their droperidol
      counterparts on postoperative day 1. CONCLUSION: Coadministration of 50 mug
      droperidol and 1 mg morphine on demand via PCA provides a morphine-sparing effect
      and reduces the frequency of postoperative nausea and vomiting.

PMID- 15950852
TI  - Visual evaluation of fade in response to facial nerve stimulation at the eyelid.
AB  - STUDY OBJECTIVE: The aim of this study is to investigate the probability of
      visual detection of fade in response to train-of-four (TOF) stimulation, double
      burst stimulation3,3 (DBS(3,3)), or DBS(3,2) at the eyelid in comparison to that
      at the thumb. DESIGN: This is a randomized single-blinded study. SETTING: The
      study took place at the University hospital. PATIENTS AND MEASUREMENTS: Sixty
      adult patients underwent general anesthesia. INTERVENTIONS AND MEASUREMENTS:
      Patients were randomly divided into either the eyelid group (n = 30) or the thumb
      group (n = 30). In the eyelid group, at the varying degrees of neuromuscular
      block caused by vecuronium, TOF, DBS(3,3), or DBS(3,2) were given at the temporal
      branch of the facial nerve, and the probability of visual detection of fade in
      response to TOF, DBS(3,3), or DBS(3,2) was determined at the eyelid. Similarly,
      in the thumb group, the probability of visual detection of fade in response to
      TOF, DBS(3,3), or DBS(3,2) was examined at the thumb. MAIN RESULTS: When the true
      TOF ratios were 0 to 0.60, the probability of detection of TOF fade in the eyelid
      group was significantly lower than in the thumb group (P < .05). At the true TOF
      ratios of 0.31 to 0.70, the probability of visual detection of DBS(3,3) fade in
      the eyelid group was significantly less than in the thumb group (P < .05). When
      the true TOF ratios were 0.81 to 1.00, the probability of detection of DBS(3,2)
      fade in the eyelid group was significantly higher than in the thumb group (P <
      .05). CONCLUSION: The probability of visual detection of fade in response to TOF
      or DBS(3,3) is lower at the eyelid than the thumb. In contrast, DBS(3,2) fade
      tends to be seen more frequently at the eyelid than at the thumb.

PMID- 15950853
TI  - Epidural analgesia improves early rehabilitation after total knee replacement.
AB  - STUDY OBJECTIVE: To compare epidural anesthesia and analgesia with spinal
      anesthesia with intravenous morphine analgesia for its effect on range of motion
      (ROM) and early rehabilitation after total knee replacement. DESIGN: Randomized
      prospective study. SETTING: Tertiary care, academic medical center. PATIENTS:
      Thirty-eight patients scheduled for total knee replacement. INTERVENTIONS:
      Patients were randomized into 2 groups. One group received spinal anesthesia with
      0.5% bupivacaine and analgesia with intravenous patient-controlled analgesia
      morphine, demand mode only. The other group was given epidural anesthesia with
      1.0% ropivacaine with 1:200,000 epinephrine and analgesia with 0.2% ropivacaine
      at 8 mL/h, maintained for 7 days. Both groups had compression stocking for deep
      venous thrombosis (DVT) prophylaxis, urinary catheter for the first 24 hours, and
      duplex scanning at days 3 and 10. The spinal group received low molecular-weight
      heparin for DVT prophylaxis. MEASUREMENTS: Data collected included pain scores at
      rest, and with ROM, frequency of DVT, and patient satisfaction. Data were
      evaluated with Wilcoxon rank sum test for continuous variables and Fisher exact
      test for categorical variables. Data were considered significant at P < .05. MAIN
      RESULTS: All 38 patients finished the study, 22 in the spinal group and 16 in the
      epidural group. There was no difference in demographics between groups. The pain
      sores at rest and with ROM were significantly less in the epidural group. ROM was
      better in the epidural group compared with the spinal group after day 1. No DVT
      was detected on day 3 or 10 in either group. No patient in either group required
      reinsertion of bladder catheter for urinary retention. CONCLUSION: By using
      epidural analgesia in the first 7 days postoperatively, we achieved improved
      early rehabilitation due to excellent pain relief effect and an antithrombotic
      effect with an efficacy comparable to low molecular-weight heparin.

PMID- 15950854
TI  - A new approach to securing a difficult airway.
AB  - The ability to provide a patent airway for gas exchange is a mandatory skill for
      the anesthesiologist. Because of variations in the anatomy and physiology of
      patients, a technique used to intubate the trachea of one patient may not be
      successful for another. Thus, it is crucial that the anesthesiologist have
      multiple ways in which to approach an airway. We first describe a new technique
      for airway management that can be used electively or in an emergent situation to
      intubate the trachea of a patient during anesthesia. We then provide 2 detailed
      case reports in which the technique was found to be helpful. We have since used
      it in more than 60 patients, without any related complications.

PMID- 15950855
TI  - Anesthetic management of a patient with tracheal neurofibroma.
AB  - A 43-year-old man with neurofibromatosis and tracheal neurofibroma of the mid
      trachea and respiratory difficulty was brought to the operating room for
      tracheostomy. After talking to the surgeons and viewing the computerized axial
      tomography, tracheal intubation was done under local anesthesia. Then, general
      anesthesia was provided for biopsy and debulking of the tumor, followed by
      tracheostomy. The patient had a number of surgeries later and the trachea was
      decannulated.

PMID- 15950856
TI  - Unusual positioning of a central venous catheter.
AB  - Central venous cannulation, with or without a flow-directed pulmonary artery
      catheter, is commonly performed in patients undergoing cardiac surgery to measure
      central filling pressure and cardiac output, and to administer medications and
      fluids. The complications of central venous cannulation are numerous and include
      malposition, arterial puncture, pneumothorax, hemothorax, chylothorax,
      extravasation of infusate, thrombophlebitis, and infection. We describe a single
      lumen catheter that was placed through the hemostatic valve of a 9F percutaneous
      introducer, which inadvertently entered the left internal mammary (internal
      thoracic) vein. The current case is unique in that it was diagnosed by
      visualization of the catheter during surgical dissection.

PMID- 15950857
TI  - Cesarean section at 28 weeks' gestation with resection of pheochromocytoma:
      perioperative antihypertensive management.
AB  - Pregnancy complicated by pheochromocytoma is potentially fatal. Pregnancy and
      labor increase the risk of hypertensive crisis as it may occur with the sudden
      release of catecholamine accompanying uterine contractility and straining.
      However, antepartum diagnosis reduces both maternal and fetal mortality, allowing
      for safe cesarean section and resection of tumor. We describe the management of
      perioperative hypertension for combined cesarean section and pheochromocytoma
      resection.

PMID- 15950858
TI  - Four different airway-management strategies in patient with Launois-Bensaude
      syndrome or Madelung's disease undergoing surgical excision of neck lipomatosis
      with a complicated postoperative course.
AB  - Launois-Bensaude syndrome, otherwise known as Madelung's disease, is a rare
      disorder characterized by fatty accumulations of the upper trunk, neck and head,
      causing serious cosmetic deformity and neck immobility. We report a case of a
      patient with Launois-Bensaude syndrome who required 4 different airway management
      strategies during his hospitalization for postoperative complications after an
      elective surgical excision of a severe neck lipomatosis. Anesthesiologists who
      treat patients with Madelung's disease should be aware of 2 major problems:
      difficult airway and increased frequency of postoperative bleeding. A proper
      choice of airway management technique is therefore necessary, including a safe
      intubation and extubation plan to reduce the consequences of airway
      complications.

PMID- 15950859
TI  - Exacerbation of preexisting neurological deficits by neuraxial anesthesia: report
      of 7 cases.
AB  - We undertook this case series to determine if preexisting neurological disease is
      exacerbated by either spinal or epidural anesthesia. In the website of the
      Arachnoiditis Foundation, we posted an offer to advise anesthesiologists in cases
      of neurological problems after either of these techniques was used. Contacts were
      made first by way of the Internet, confirmed by telephone, and maintained by fax,
      e-mail, or by special mail. Patients here described were cared for and observed
      by one of the authors, in a hospital, in Argentina or in Mexico. A total of 7
      adult, ASA physical status I and II patients, including 3 men and 4 women, with
      subtle symptoms of neurological disease before anesthesia, are described. Two
      patients had continuous lumbar epidural anesthesia, 3 had spinals; in 2 more,
      attempted epidural blocks led to accidental dural puncture and were converted to
      subarachnoid anesthetics. All patients accepted neuraxial anesthesia without
      informing the anesthesiologists that they had mild neurological symptoms before
      surgery. Because anesthesiologists did not specifically inquire about subclinical
      neurological symptoms or prior neurological disease, anesthesiologists are
      advised to carefully inquire about prior neurological disease whether neuraxial
      anesthesia techniques are considered.

PMID- 15950860
TI  - The enhanced postoperative care system.
AB  - The perioperative care system is a continuum that includes preoperative patient
      evaluation, operating room scheduling, the operation itself, and postoperative
      care. This costly fast-paced system requires its various components to function
      efficiently and interact effectively. This review explores the interrelation
      between the operational elements of the enhanced care postoperative care system
      (intensive care units, intermediate care units, postanesthesia care units, and
      monitored floor beds) and other perioperative care activities. This care system
      provides patients with enhanced (from routine floor) nursing and medical care,
      continuous physiological monitoring, and sophisticated treatments (eg, continuous
      infusion of vasoactive substances). A management, rather than clinical, approach
      is used to provide insight into the operations of the perioperative care system
      so that bottlenecks to patient flow may be identified and eliminated. Emphasis is
      placed on the need to switch from a "fiefdom" mentality, where each component of
      the system acts independently and defensively, to systems thinking, in which
      complex interrelated patterns are identified, analyzed, and optimized.

PMID- 15950861
TI  - Paranasal sinus barotrauma in general anesthesia: special attention.

PMID- 15950862
TI  - Operating room turnover times.

PMID- 15950863
TI  - Airway exchange catheter and laser endotracheal tube.

PMID- 15950864
TI  - Use of double-sided tape to secure a tracheal tube.

PMID- 15950865
TI  - IUBMB: the first half-century.

PMID- 15950866
TI  - Regulation of transcription: from lambda to eukaryotes.

PMID- 15950867
TI  - The discovery of split genes and RNA splicing.

PMID- 15950868
TI  - The ribosome revealed.

PMID- 15950869
TI  - Regulated protein degradation.

PMID- 15950870
TI  - Protein phosphorylation in signaling--50 years and counting.

PMID- 15950871
TI  - RNA silencing.

PMID- 15950872
TI  - Mitochondrial DNA, aconitase 'wraps' it up.
AB  - Mitochondria are the sites of many essential biochemical reactions, an important
      subset of which require proteins encoded in the mitochondrial DNA (mtDNA). How
      mtDNA is regulated in response to changing cellular demands is largely unknown. A
      recent study documents that the mitochondrial TCA-cycle enzyme aconitase is
      associated with protein-mtDNA complexes called nucleoids. In this novel context,
      aconitase functions to stabilize mtDNA, perhaps by reversibly remodeling
      nucleoids to directly influence mitochondrial gene expression in response to
      changing cellular metabolism.

PMID- 15950873
TI  - A window of opportunity: timing protein degradation by trimming of sugars and
      ubiquitins.
AB  - Of the many post-translational modifications of proteins, ubiquitination and N
      glycosylation stand out because they are polymeric additions. In contrast to
      single-unit modifications, the fate of the modified protein is determined by the
      dynamic equilibrium of polymerization versus depolymerization, rather than by the
      initial addition itself. Notably, it is the trimming of sugar chains and
      elongation of polyubiquitin that target the protein to degradation. Recent
      research suggests that, for each process, special receptors recognize chains that
      reach an appropriate length and commit the conjugated substrate for proteasomal
      disposal. We propose that the 'magic numbers' are loss of at least three mannose
      residues from the initial chain, or extension to at least four ubiquitins.
      Although these processes are compartmentalized to either side of the endoplasmic
      reticulum (ER) membrane, some proteins are sequentially subjected to both because
      they transverse this membrane for ER-associated degradation.

PMID- 15950874
TI  - Adenosyltransferase: an enzyme and an escort for coenzyme B12?
AB  - Many organic cofactors are both rare and reactive. They are usually in low
      abundance, which poses problems for efficient collision-based targeting to
      dependent enzymes, whereas their reactivity is problematic for side reactions.
      Sequestration and escorted delivery presents one solution to this conundrum, but
      such porters, if they exist, are mostly unknown. In humans, the mitochondrial
      enzyme methylmalonyl-coenzyme A mutase uses coenzyme B(12) (adenosylcobalamin)
      but would be inactive if bound to the cofactor precursor that is delivered to the
      mitochondrion. Adenosyltransferase converts cob(II)alamin to coenzyme B(12).
      Based on kinetic evidence for interaction between the two enzymes, the 40-fold
      greater affinity for coenzyme B(12) and the higher coordination number for cobalt
      in the mutase, we propose that the adenosyltransferase is a dual-function
      protein: an enzyme that synthesizes coenzyme B(12) and a chaperone that delivers
      it.

PMID- 15950875
TI  - The LDL receptor: how acid pulls the trigger.
AB  - The low-density lipoprotein receptor normally carries lipoprotein particles into
      cells, and releases them upon delivery to the low pH milieu of the endosome.
      Recent structural and functional studies of the receptor, combined with the
      plethora of prior knowledge about normal receptor function and the effects of
      disease-associated mutations that cause familial hypercholesterolemia, reveal a
      detailed molecular model for how the acidic environment of the endosome triggers
      the release of bound lipoprotein particles. Remarkably, the receptor dynamically
      interconverts between open (ligand-active) and closed (ligand-inactive)
      conformations in response to pH, relying on a specific arrangement of fixed and
      flexible interdomain connections to facilitate efficient binding and release of
      its lipoprotein ligands.

PMID- 15950876
TI  - G-protein-directed ligand discovery with peptide combinatorial libraries.
AB  - Modulators of G-protein signaling have a central role in controlling cell
      physiology and represent over half of all marketed prescription drugs. G-protein
      pathways have traditionally been targeted by developing ligands to the
      extracellular surface of a small subset of the estimated approximately 1000 G
      protein-coupled receptors in humans. The intracellular machinery, consisting of
      the cytosolic receptor surfaces and heterotrimeric G proteins, provides an
      equivalent diversity of targets that has remained relatively unexplored until
      now. This review summarizes recent efforts using combinatorial peptide libraries
      to develop new G-protein signaling modulators targeting intracellular components.

PMID- 15950877
TI  - Glycine transporters: essential regulators of neurotransmission.
AB  - Glycine has important neurotransmitter functions at inhibitory and excitatory
      synapses in the vertebrate central nervous system. The effective synaptic
      concentrations of glycine are regulated by glycine transporters (GlyTs), which
      mediate its reuptake into nerve terminals and adjacent glial cells. GlyTs are
      members of the Na(+)/Cl(-)-dependent transporter family, whose activities and
      subcellular distributions are regulated by phosphorylation and interactions with
      other proteins. The analysis of GlyT knockout mice has revealed distinct
      functions of individual GlyT subtypes in synaptic transmission and provided
      animal models for two hereditary human diseases, glycine encephalopathy and
      hyperekplexia. Selective GlyT inhibitors could be of therapeutic value in
      cognitive disorders, schizophrenia and pain.

PMID- 15950878
TI  - A gamut of loops: meandering DNA.
AB  - Nucleoprotein complexes comprising short DNA loops (150 base pairs or less) are
      involved in a wide variety of DNA transactions (e.g. transcription regulation,
      replication and recombination) in both prokaryotes and eukaryotes, and also can
      be useful in designing nanostructures. In these higher-order nucleoprotein
      complexes, proteins bound to spatially separated sites on a DNA interact with
      each other by looping out the relatively stiff intervening DNA. Recent
      technological developments have enabled determination of DNA trajectories in a
      few DNA-loop-containing regulatory complexes. Results show that, in a given
      system, a specific DNA trajectory is preferred over others.

PMID- 15950879
TI  - Formin proteins: a domain-based approach.
AB  - Formin proteins are potent regulators of actin dynamics. Most eukaryotes have
      multiple formin isoforms, suggesting diverse cellular roles. Formins are modular
      proteins, containing a series of domains and functional motifs. The Formin
      homology 2 (FH2) domain binds actin filament barbed ends and moves processively
      as these barbed ends elongate or depolymerize. The FH1 domain influences FH2
      domain function through binding to the actin monomer-binding protein, profilin.
      Outside of FH1 and FH2, amino acid similarity between formins decreases,
      suggesting diverse mechanisms for regulation and cellular localization. Some
      formins are regulated by auto-inhibition through interaction between the
      diaphanous inhibitory domain (DID) and diaphanous auto-regulatory domain (DAD),
      and activated by Rho GTPase binding to GTPase-binding domains (GBD). Other
      formins lack DAD, DID and GBD, and their regulatory mechanisms await elucidation.

PMID- 15950880
TI  - The imagination: cognitive, pre-cognitive, and meta-cognitive aspects.
AB  - This article is an attempt to situate imagination within consciousness complete
      with its own pre-cognitive, cognitive, and meta-cognitive domains. In the first
      sections we briefly review traditional philosophical and psychological
      conceptions of the imagination. The majority have viewed perception and
      imagination as separate faculties, performing distinct functions. A return to a
      phenomenological account of the imagination suggests that divisions between
      perception and imagination are transcended by precognitive factors of sense of
      reality and non-reality where perception and imagination play an indivisible
      role. In fact, both imagination and perception define sense of reality jointly
      according to what is possible and not possible. Absorption in a possible world
      depends on the strengths of alternative possibilities, and the relationship
      between core and marginal consciousness. The model may offer a parsimonious
      account of different states and levels of imaginal consciousness, and of how
      "believed-in imaginings" develop and become under some circumstances "lived-in
      experiences."

PMID- 15950881
TI  - Unconscious word-stem completion priming in a mirror-masking paradigm.
AB  - The aim of this study was to investigate unconscious priming by the use of a
      spatial mirror-masking paradigm. Words and nonwords with no under-length letters
      are mirrored at their horizontal axis. The results are figures of geometric-like
      forms that contain letters in their upper part. In the three experiments reported
      in this study, a priming procedure used such mirrored words and nonwords as
      primes. Participants were ignorant of the nature of the construction of the
      stimuli. Perceptual reports of the participants revealed that they did not
      realize that words were hidden in the primes. Nevertheless, they showed priming
      in all three experiments. Priming effects were replicated with prime-target SOAs
      of between 1 and 3 s. Functional dissociations were found between ignorant and
      informed participants. Informed groups showed perceptual and semantic priming,
      while ignorant groups showed only perceptual priming.

PMID- 15950882
TI  - Automatic and controlled semantic processing: a masked prime-task effect.
AB  - A classical definition of automaticity establishes that automatic processing
      occurs without attention or consciousness, and cannot be controlled. Previous
      studies have demonstrated that semantic priming can be reduced if attention is
      directed to a low-level of analysis. This finding suggests that semantic
      processing is not automatic since it can be controlled. In this paper, we present
      two experiments that demonstrate that semantic processing may occur in the
      absence of attention and consciousness. A negative semantic priming effect was
      found when a low-level prime-task was required and when a masked lexical decision
      prime-task was performed (Experiment 1). This paper also discusses the
      limitations of the inhibitory mechanism involved in negative semantic priming
      effect.

PMID- 15950883
TI  - Hypnotic susceptibility, baseline attentional functioning, and the Stroop task.
AB  - According to the theoretical framework relating hypnosis to attention, baseline
      attentional functioning in highly hypnotizable individuals should be more
      efficient than in low hypnotizable individuals. However, previous studies did not
      find differences in Stroop-like tasks in which the measure indicative of the
      Stroop interference effect was based on response latencies. This study was
      designed to determine whether subjects with different levels of hypnotic
      susceptibility show differences in baseline attentional functioning. To assess
      this hypothesis, high, medium, and low hypnotizable subjects performed a Stroop
      task designed to evaluate accuracy performance, before being subjected to
      hypnotic induction. Results showed that the Stroop interference effect was
      smaller in high hypnotizable subjects than in low hypnotizable subjects, whereas
      it was not different between high, and medium hypnotizable subjects. This outcome
      supports the notion that baseline attentional functioning is related to hypnotic
      susceptibility.

PMID- 15950884
TI  - Does 'hypnosis' by any other name smell as sweet? The efficacy of 'hypnotic'
      inductions depends on the label 'hypnosis'.
AB  - Hypnosis is associated with profound changes in conscious experience and is
      increasingly used as a cognitive tool to explore neuropsychological processes.
      Studies of this sort typically employ suggestions following a hypnotic induction
      to produce changes in perceptual experience and motor control. It is not clear,
      however, to what extent the induction procedure serves to facilitate suggested
      phenomena. This study investigated the effect on suggestibility of (a) a hypnotic
      induction and (b) labelling that procedure 'hypnosis.' Suggestibility of
      participants was tested before and after an adapted hypnotic procedure, which was
      either labelled as 'hypnosis' or as 'relaxation.' The hypnotic procedure produced
      a modest increase in suggestibility when it was called 'relaxation,' but a very
      significant increase if it was labelled 'hypnosis.' The results are important for
      both clinical and experimental applications and indicate that labelling an
      induction procedure 'hypnosis' is an important determinant of subsequent
      responses to suggestion.

PMID- 15950885
TI  - Activating the critical lure during study is unnecessary for false recognition.
AB  - Participants studied lists of nonwords (e.g., froost, floost, stoost, etc.) that
      were orthographic-phonologically similar to a nonpresented critical lure, which
      was also a nonword (e.g., ploost). Experiment 1 showed a high level of false
      recognition for the critical lure. Experiment 2 showed that the false recognition
      effect was also present for forewarned participants who were informed about the
      nature of the false recognition effect and told to avoid making false recognition
      judgments. The present results show that false recognition effects can be
      obtained even when the critical lure itself is not stored during study. This
      finding is problematic for accounts that attribute false memories to implicit
      associative responses or spreading activation but is easily explained by global
      familiarity models of recognition memory.

PMID- 15950886
TI  - Event-related potential evidence for multiple causes of the revelation effect.
AB  - Asking people to discover the identity of a recognition test probe immediately
      before making a recognition judgment increases the probability of an old
      judgment. To inform theories of this "revelation effect," event-related
      potentials (ERPs) were recorded for revealed and intact test items across two
      experiments. In Experiment 1, we used a revelation effect paradigm where half of
      the test probes were presented as anagrams (i.e., a related task) and the other
      items were presented intact. The pattern of ERP results from this experiment
      suggested that revealing an item decreases initial familiarity levels and caused
      the revealed items to elicit similar levels of activity. In Experiment 2, half of
      the probes were preceded by an addition task (i.e., an unrelated task). The
      pattern of ERP effects in this study were distinct from those observed in
      Experiment 1. More specifically, revealed item ERPs were more negative than
      intact ERPs at frontal electrodes and more positive at parietal electrodes early
      in the interval. Later in the epoch, revealed item ERPs were more negative than
      intact items. These data suggest that related tasks decrease familiarity and
      alter the signal-to-noise ratio of old and new items, whereas unrelated tasks
      affect processing in a different way (perhaps by changing decision processes)
      that also results in the revelation effect. The implications for current theories
      of the revelation effect are discussed.

PMID- 15950887
TI  - Accuracy of familiarity decisions to famous faces perceived without awareness
      depends on attitude to the target person and on response latency.
AB  - Stone and Valentine (2004) presented masked 17 ms faces in simultaneous pairs of
      one famous and one unfamiliar face. Accuracy in selecting the famous face was
      higher when the famous person was regarded as "good" or liked than when regarded
      as "evil" or disliked. Experiment 1 attempted to replicate this phenomenon, but
      produced a different pattern of results. Experiment 2 investigated alternative
      explanations and found evidence supporting only the effect of response latency:
      responses made soon after stimulus onset were more accurate to liked than to
      disliked faces, whereas responses made after a longer delay were equally accurate
      to disliked faces. It appears that the effect of negative valence was corrected
      within the space of a few hundred milliseconds. Experiment 3, using an affective
      priming paradigm, supported the concept that an early-arising effect of valence
      is corrected if it is misleading to the directed task.

PMID- 15950888
TI  - Procedural memory in dissociative identity disorder: when can inter-identity
      amnesia be truly established?
AB  - In a serial reaction time task, procedural memory was examined in Dissociative
      Identity Disorder (DID). Thirty-one DID patients were tested for inter-identity
      transfer of procedural learning and their memory performance was compared with 25
      normal controls and 25 controls instructed to simulate DID. Results of patients
      seemed to indicate a pattern of inter-identity amnesia. Simulators, however, were
      able to mimic a pattern of inter-identity amnesia, rendering the results of
      patients impossible to interpret as either a pattern of amnesia or a pattern of
      simulation. It is argued that studies not including DID-simulators or simulation
      free memory tasks, should not be taken as evidence for (or against) amnesia in
      DID.

PMID- 15950889
TI  - Common fronto-parietal activity in attention, memory, and consciousness: shared
      demands on integration?
AB  - Fronto-parietal activity has been frequently observed in fMRI and PET studies of
      attention, working memory, and episodic memory retrieval. Several recent fMRI
      studies have also reported fronto-parietal activity during conscious visual
      perception. A major goal of this review was to assess the degree of anatomical
      overlap among activation patterns associated with these four functions. A second
      goal was to shed light on the possible cognitive relationship of processes that
      relate to common brain activity across functions. For all reviewed functions we
      observed a consistent and overlapping pattern of brain activity. The overlap was
      most pronounced for the bilateral parietal cortex (BA 7 and BA 40; close to the
      intraparietal sulcus), and dorsolateral prefrontal cortex (right BA 9 and left BA
      6). The common fronto-parietal activity will be discussed in terms of processes
      related to integration of distributed representations in the brain.

PMID- 15950890
TI  - [Fetal/neonatal allo-immune thrombocytopenias: the unsolved questions].
AB  - The allo-immune thrombocytopenias are the major cause of severe thrombocytopenia
      in the fetus and the neonate. The frequency of this affection has been evaluated
      to be 1 out of 800 to 1000 live births. The deleterious consequences of severe
      thrombocytopenia are intracranial hemorrhages leading to death or neurological
      sequelae. Progress in platelet immunology and antenatal medicine has allowed a
      better diagnosis of this affection and development of the antenatal management of
      high-risk pregnancies. Nevertheless there are unsolved questions, particularly
      concerning the mechanism of the maternal immunization, the laboratory
      difficulties for the identification of the alloantibodies, the absence of
      antenatal management standardization.

PMID- 15950891
TI  - [Management of depots for blood products in health establishments. Management of
      labile blood products, supplies, tracking].

PMID- 15950892
TI  - [Indications for labile blood products and the physiology of transfusion in
      surgery].

PMID- 15950893
TI  - [Progress in transfusion for storage of platelets].
AB  - Improvement of platelet concentrates efficacy and safety depends on platelet
      storage conditions and their improvement: storage in the cold, additive solutions
      and pathogen inactivation.

PMID- 15950894
TI  - Automated segmentation of the optic nerve head for diagnosis of glaucoma.
AB  - Glaucoma is the second most common cause of blindness worldwide. Low awareness
      and high costs connected to glaucoma are reasons to improve methods of screening
      and therapy. A well-established method for diagnosis of glaucoma is the
      examination of the optic nerve head using scanning-laser-tomography. This system
      acquires and analyzes the surface topography of the optic nerve head. The
      analysis that leads to a diagnosis of the disease depends on prior manual
      outlining of the optic nerve head by an experienced ophthalmologist. Our
      contribution presents a method for optic nerve head segmentation and its
      validation. The method is based on morphological operations, Hough transform, and
      an anchored active contour model. The results were validated by comparing the
      performance of different classifiers on data from a case-control study with
      contours of the optic nerve head manually outlined by an experienced
      ophthalmologist. We achieved the following results with respect to glaucoma
      diagnosis: linear discriminant analysis with 27.7% estimated error rate for
      automated segmentation (aut) and 26.8% estimated error rate for manual
      segmentation (man), classification trees with 25.2% (aut) and 22.0% (man) and
      bootstrap aggregation with 22.2% (aut) and 13.4% (man). It could thus be shown
      that our approach is suitable for automated diagnosis and screening of glaucoma.

PMID- 15950895
TI  - Extracting and visualizing physiological parameters using dynamic contrast
      enhanced magnetic resonance imaging of the breast.
AB  - An analysis procedure is presented that enables the acquisition and visualization
      of physiologically relevant parameters using dynamic contrast-enhanced magnetic
      resonance imaging. The first stage of the process involves the use of a signal
      model that relates the measured magnetic resonance signal to the contrast agent
      concentration. Since the model requires knowledge of the longitudinal relaxation
      time T(1), a novel optimization scheme is presented which ensures a reliable
      measurement. Pharmacokinetic modelling of the observed contrast agent uptake is
      then performed to obtain physiological parameters relating to microvessel leakage
      permeability and volume fraction and the assumptions made in the derivation of
      these parameters are discussed. A simple colour representation is utilized that
      enables the relevant physiological information to be conveyed to the clinician in
      a visually efficient and meaningful manner. A second representation, based on
      vector maps, is also devised and it is demonstrated how this can be used for
      malignant tumour segmentation. Finally, the procedure is applied to 14 pre- and
      post-chemotherapy breast cases to demonstrate the clinical value of the
      technique. In particular, the apparent improved representation of tissue
      vascularity when compared to conventional methods and the implications for this
      in treatment assessment are discussed.

PMID- 15950896
TI  - Phase mutual information as a similarity measure for registration.
AB  - This article describes a new method for non-rigid alignment of multimodal images.
      Multimodal image registration is most often accomplished by modelling, in some
      sense, an intensity mapping between the images. Here, the alternative strategy of
      modelling a relationship between local image phase is introduced. This method is
      intrinsically image feature based, and searches for relationships between feature
      appearances, rather than tissue class intensity. This enables registration of
      modalities for which image intensity is not a simple function of tissue class,
      for example ultrasound. It is also demonstrated that this method performs
      comparably to an intensity method even when the images are related by a simple
      intensity transform, but that the phase method is significantly more robust to
      image artifacts which corrupt the ideal intensity mapping.

PMID- 15950897
TI  - Coevolution of cancer and stromal cellular responses.
AB  - It is now becoming apparent that multiple types of stromal cells, including
      macrophages, mast cells, adipocytes, and fibroblasts make pivotal contributions
      to carcinogenesis. In the May 6 issue of Cell, Orimo and colleagues (Orimo et
      al., 2005) show that carcinoma-associated fibroblasts can promote epithelial
      tumorigenesis by secreting the chemokine SDF-1alpha (CXCL12). SDF-1alpha
      stimulates carcinoma cell proliferation and recruitment of endothelial precursor
      cells.

PMID- 15950898
TI  - Master or slave: the complex relationship of RBP2 and pRb.
AB  - The retinoblastoma protein or its regulators are altered in most human cancers.
      Although commonly thought of as solely a repressor of E2F-dependent transcription
      and cell cycle progression, pRb has gained notoriety in recent years as a key
      actor in cellular differentiation programs. In the June issue of Molecular Cell,
      Benevolenskaya et al. report that a long-known but poorly understood pRb
      interactor, RBP2, acts as an inhibitor of differentiation contributing to pRb's
      role as a coordinator of differentiation and cell cycle exit. Loss of pRb may
      unleash RBP2, maintaining cells in a poorly differentiated progenitor state that
      is prerequisite to tumor formation.

PMID- 15950899
TI  - A functional approach to questions about life, death, and phosphorylation.
AB  - The success of the family of kinases as targets for small-molecule cancer
      therapeutics is probably best illustrated by the efficacy of the drug Gleevec. In
      spite of this, the function of many of the kinases in the mammalian genome
      remains unknown. In a recent paper, MacKeigan and colleagues report a functional
      genetic screen using RNA interference to identify kinases and phosphatases
      involved in programmed cell death (MacKeigan et al., 2005). Functional annotation
      is a prerequisite for selection of new drug targets. Such studies may therefore
      lay the foundation for the next generation of cancer drugs.

PMID- 15950901
TI  - Therapeutic targeting of the tumor microenvironment.

PMID- 15950900
TI  - What has senescence got to do with cancer?
AB  - Cancer therapeutics are primarily thought to work by inducing apoptosis in tumor
      cells. However, various tumor suppressors and oncogenes have been shown to
      regulate senescence in normal cells, and senescence bypass appears to be an
      important step in the development of cancer. Cellular senescence limits the
      replicative capacity of cells, thus preventing the proliferation of cells that
      are at different stages of malignancy. A recent body of evidence suggests that
      induction of senescence can be exploited as a basis for cancer therapy.

PMID- 15950902
TI  - CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and
      invasiveness.
AB  - CUTL1, also known as CDP, Cut, or Cux-1, is a homeodomain transcriptional
      regulator known to be involved in development and cell cycle progression. Here we
      report that CUTL1 activity is associated with increased migration and
      invasiveness in numerous tumor cell lines, both in vitro and in vivo.
      Furthermore, we identify CUTL1 as a transcriptional target of transforming growth
      factor beta and a mediator of its promigratory effects. CUTL1 activates a
      transcriptional program regulating genes involved in cell motility, invasion, and
      extracellular matrix composition. CUTL1 expression is significantly increased in
      high-grade carcinomas and is inversely correlated with survival in breast cancer.
      This suggests that CUTL1 plays a central role in coordinating a gene expression
      program associated with cell motility and tumor progression.

PMID- 15950903
TI  - Activation of RalA is critical for Ras-induced tumorigenesis of human cells.
AB  - RalGEFs were recently shown to be critical for Ras-mediated transformed and
      tumorigenic growth of human cells. We now show that the oncogenic activity of
      these proteins is propagated by activation of one RalGEF substrate, RalA, but
      blunted by another closely related substrate, RalB, and that the oncogenic
      signaling requires binding of the RalBP1 and exocyst subunit effector proteins.
      Knockdown of RalA expression impeded, if not abolished, the ability of human
      cancer cells to form tumors. RalA was also commonly activated in a panel of cell
      lines from pancreatic cancers, a disease characterized by activation of Ras.
      Activation of RalA signaling thus appears to be a critical step in Ras-induced
      transformation and tumorigenesis of human cells.

PMID- 15950904
TI  - Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and
      activate p53 in cells.
AB  - The p53 tumor suppressor protein is regulated by its interaction with HDM2, which
      serves as a ubiquitin ligase (E3) to target p53 for degradation. We have
      identified a family of small molecules (HLI98) that inhibits HDM2's E3 activity.
      These compounds show some specificity for HDM2 in vitro, although at higher
      concentrations effects on unrelated RING and HECT domain E3s are detectable,
      which could be due, at least in part, to effects on E2-ubiquitin thiol-ester
      levels. In cells, the compounds allow the stabilization of p53 and HDM2 and
      activation of p53-dependent transcription and apoptosis, although other p53
      independent toxicity was also observed.

PMID- 15950905
TI  - Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
AB  - PIK3CA is mutated in diverse human cancers, but the functional effects of these
      mutations have not been defined. To evaluate the consequences of PIK3CA
      alterations, the two most common mutations were inactivated by gene targeting in
      colorectal cancer (CRC) cells. Biochemical analyses of these cells showed that
      mutant PIK3CA selectively regulated the phosphorylation of AKT and the forkhead
      transcription factors FKHR and FKHRL1. PIK3CA mutations had little effect on
      growth under standard conditions, but reduced cellular dependence on growth
      factors. PIK3CA mutations resulted in attenuation of apoptosis and facilitated
      tumor invasion. Treatment with the PI3K inhibitor LY294002 abrogated PIK3CA
      signaling and preferentially inhibited growth of PIK3CA mutant cells. These data
      have important implications for therapy of cancers harboring PIK3CA alterations.

PMID- 15950906
TI  - Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway.
AB  - Epidermal growth factor receptor (EGFR) exists in the nucleus of highly
      proliferative cells where it functions as a transcription factor. Although EGFR
      has transactivational activity, it lacks a DNA binding domain and, therefore, may
      require a DNA binding transcription cofactor for its transcriptional function.
      Here, we report that EGFR physically interacts with signal transducers and
      activators of transcription 3 (STAT3) in the nucleus, leading to transcriptional
      activation of inducible nitric oxide synthase (iNOS). In breast carcinomas,
      nuclear EGFR positively correlates with iNOS. This study describes a mode of
      transcriptional control involving cooperated efforts of STAT3 and nuclear EGFR.
      Our work suggests that the deregulated iNOS/NO pathway may partly contribute to
      the malignant biology of tumor cells with high levels of nuclear EGFR and STAT3.

PMID- 15950907
TI  - Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by
      p27(Kip1) and p21(Cip1).
AB  - p27(Kip1) and p21(Cip1) are thought to suppress tumor growth and prevent cell
      cycle progression by inhibiting Cdk2-cyclin E/A kinases. Since Cdk2 is
      dispensable for mitotic cell division, we analyzed the activity of these
      inhibitors in Cdk2-deficient cells. Ectopic expression of p27(Kip1) or p21(Cip1)
      efficiently inhibits cell cycle progression of Cdk2(-/-) fibroblasts. Loss of
      p27(Kip1) or p21(Cip1) confers similar proliferative advantages to Cdk2(+/+) and
      Cdk2(-/-) cells. Moreover, Cdk2 is dispensable for p21(Cip1)-induced cell cycle
      arrest after DNA damage. Finally, ablation of Cdk2 in p27(Kip1) null mice does
      not suppress their phenotypic defects, including development of pituitary tumors.
      These results indicate that Cdk2 is not an essential target for p27(Kip1) and
      p21(Cip1) in cell cycle inhibition and tumor suppression.

PMID- 15950908
TI  - Analysis of oligonucleotide annealing by electrophoresis in agarose gels using
      sodium borate conductive medium.

PMID- 15950909
TI  - Direct electrochemistry and electrocatalysis of heme proteins immobilized on gold
      nanoparticles stabilized by chitosan.
AB  - Three heme proteins, myoglobin, hemoglobin, and cytochrome c, have been adsorbed
      onto chitosan-stabilized gold nanoparticles (Chit-Aus) modified Au electrode via
      a molecule bridge like cysteine. UV-vis spectra indicated that the proteins on
      Chit-Aus films retained near-native secondary structures. The fabricated
      procedures and electrochemical behaviors of proteins on such an interface were
      characterized with electrochemical impedance spectra and cyclic voltammetric
      techniques. It was demonstrated that Chit-Aus film could not only offer a
      friendly environment to immobilize protein molecules but also enhance the
      electron transfer ability between protein molecules and underlying electrode. The
      effects of scan rate and pH on the electrochemical behaviors of each heme protein
      are discussed in detail. The resultant electrode displayed an excellent
      electrocatalytic response to the reduction of H(2)O(2), long-term stability, and
      good reproducibility.

PMID- 15950910
TI  - Phosphorimaging detection and quantitation for isotopic ion flux assays.
AB  - A 96-well-microplate-based ion flux method utilizing readily available
      autoradiographic phosphorimaging detection is described. Nicotinic acetylcholine
      receptor-mediated (22)Na influx in four cultured cell lines provided satisfactory
      concentration-response data for epibatidine and several other nicotinic agonists.
      The data were consistent with data obtained using standard 6-well assays. Assays
      for nicotinic-receptor-mediated (86)Rb efflux produced data similar to data
      obtained with the (22)Na influx assay. However, assays for (45)Ca influx were not
      successful, although (45)Ca was readily detected and quantified. Voltage-gated
      sodium channel-mediated (22)Na influx in a neuroblastoma cell line allowed assay
      of the effects of such sodium channel activators as batrachotoxin and a
      pumiliotoxin B/scorpion venom combination. Phosphorimaging detection allows for
      reliable beta counting of up to 1,200 simultaneous samples with excellent
      sensitivity and is amenable for application to high-throughput screening.

PMID- 15950911
TI  - Proximity ligation assays for sensitive and specific protein analyses.

PMID- 15950912
TI  - Effect of anticoagulants on the determination of plasma matrix metalloproteinase
      (MMP)-2 and MMP-9 activities.

PMID- 15950913
TI  - Dual-targeted labeling of proteins using cysteine and selenomethionine residues.
AB  - A new strategy for dual site-selective labeling of proteins that uses
      metabolically incorporated selenomethionine as a target for covalent modification
      by iodoacetamide derivatives, forming selenonium salts, is described. In the
      absence of free cysteine, labeling is specific and efficient. Dual-targeted
      labeling of a protein can be achieved with combinations of unique cysteine and
      methionine residues, if the cysteine is labeled first with a maleimide or another
      reagent that does not react with the selenomethionine. The method should be
      useful in biophysical applications such as fluorescence energy transfer.

PMID- 15950914
TI  - Development of a direct and sensitive detection method for DNA-binding proteins
      based on electrophoretic mobility shift assay and iodoacetamide derivative
      labeling.

PMID- 15950915
TI  - Sensitivity enhancement of surface plasmon resonance biosensing of small
      molecules.
AB  - Surface plasmon resonance (SPR) biosensor formats using gold nanoparticle or
      protein signal amplification for the sensitive assay of small molecules were
      developed using progesterone as a model compound. Progesterone was immobilized to
      a dextran surface in the Biacore biosensor through in situ covalent
      immobilization using an oligoethylene glycol linker attached to the 4 position of
      the steroid. This surface produced stable antibody binding for in excess of 1100
      assay cycles. Using this surface, assays were developed for progesterone using 10
      and 20-nm gold-streptavidin labels attached to biotinylated monoclonal antibody
      in both label prebinding and sequential binding formats. Prelabeling formats gave
      no signal enhancement but produced assays with limits of detection of 143 pg/ml,
      compared with approximately 1 ng/ml in previous studies. Sequential binding
      formats gave signal enhancements of 2.2-fold over the monoclonal antibody and a
      limit of detection of 23.1 pg/ml. It was found that secondary antibody labeling
      gave 8.1-fold signal enhancements and a limit of detection of 20.1 pg/ml, whereas
      use of secondary antibody-25 nm gold complexes provided more signal enhancement
      (13-fold) and a further improvement in limit of detection of 8.6 pg/ml.

PMID- 15950916
TI  - Enhanced green fluorescent protein as an alternative control reporter to Renilla
      luciferase.

PMID- 15950917
TI  - Frequency-domain fluorescence spectroscopy using 280-nm and 300-nm light-emitting
      diodes: measurement of proteins and protein-related fluorophores.

PMID- 15950919
TI  - [The genetics of colorectal cancer].

PMID- 15950918
TI  - SPOT synthesis: reliability of array-based measurement of peptide binding
      affinity.
AB  - Peptide arrays prepared by the SPOT synthesis technology have emerged as a
      proteomic tool to study molecular recognition and identify biologically active
      peptides. However, it was previously not clear how accurately signal intensities
      obtained by probing peptide arrays for protein binding really reflect the
      dissociation constants of the protein-peptide complexes. Using the monoclonal
      antibody CB4-1 as a model system, we systematically compared dissociation
      constants of antibody-peptide complexes with signal intensities obtained using
      the SPOT technology. By analyzing a set of peptides possessing different
      affinities to the antibody, we determined the strengths of the SPOT screening
      method. The accuracy of the measured results was improved by taking regional
      trends in the membrane surface into account. A model based on the mass action law
      compares well with the experimental results. Interestingly, the applied
      concentrations of the binding partners do not directly correspond to the
      effective concentrations in the assay. We show that the SPOT technology is an
      accurate method for assigning the spots' measured signal intensities to three
      different binding affinity classes. The dissociation constants of the
      intermediate region were found to be between pK(dis)=5 and pK(dis)=7. Altering
      the experimental parameters causes a directed change of this region.

PMID- 15950920
TI  - [Laparoscopic ileal pouch-anal anastomosis].
AB  - Total coloproctectomy with ileal pouch-anal anastomosis is the operation of
      choice for both ulcerative colitis and familial adenomatous polyposis. In
      experienced teams, it is now possible to do this operation through a laparoscopic
      approach. Laparoscopy allows to perform the same operation than during open
      surgery, but with reduction of the surgical trauma, especially for the abdominal
      wound.

PMID- 15950921
TI  - Human tartrate-resistant acid phosphatase becomes an effective ATPase upon
      proteolytic activation.
AB  - Proteolytic cleavage in an exposed loop of human tartrate-resistant acid
      phosphatase (TRAcP) with trypsin leads to a significant increase in activity. At
      each pH value between 3.25 and 8.0 the cleaved enzyme is more active. Substrate
      specificity is also influenced by proteolysis. Only the cleaved form is able to
      hydrolyze unactivated substrates efficiently, and at pH >6 cleaved TRAcP acquires
      a marked preference for ATP. The cleaved enzyme also has altered sensitivity to
      inhibitors. Interestingly, the magnitude and mode of inhibition by fluoride
      depends not only on the proteolytic state but also pH. The combined kinetic data
      imply a role of the loop residue D158 in catalysis in the cleaved enzyme.
      Notably, at low pH this residue may act as a proton donor for the leaving group.
      In this respect the mechanism of cleaved TRAcP resembles that of sweet potato
      purple acid phosphatase.

PMID- 15950922
TI  - Identification of the promoter region of the parathyroid hormone receptor gene
      responsible for transcriptional suppression by insulin-like growth factor-I.
AB  - We investigated parathyroid hormone (PTH)/PTH-related protein receptor (PTH1R)
      gene suppression induced by insulin-like growth factor (IGF)-I using a rat
      osteoblast-like cell line (UMR-106). Observations were made with PD98059, a
      specific ERK signaling pathway inhibitor, and UMR-106 cells transfected with
      dominant negative or constitutively active forms of MAP kinase kinase. IGF-I
      inhibited PTH1R gene expression via an ERK1/2 MAP kinase pathway. We cloned the 8
      kb promoter region of the rat PTH1R gene and characterized the U3 promoter, a
      major IGF-I-responsive promoter among the two present in rat osteoblasts. The IGF
      I-suppressive region was between +1 and +25, identical to the previously
      described PTH-suppressive region (PTHSR). Gel mobility-shift detected a specific
      DNA-protein complex decreased by IGF-I. Mutation involving a three base sequence
      (+1 to +3) among more than 3.5 kb constituting the PTH1R promoter region
      completely abolished IGF-I action. Thus, IGF-I signaling may act at the
      osteoblast exon U3 transcription initiation site to repress the transcriptional
      activity.

PMID- 15950923
TI  - Thermal inactivation of the reductase domain of cytochrome P450 BM3.
AB  - Although the reductase domain of cytochrome P450 BM3 (BMR) catalyzes the
      reduction of cytochrome c and 2,6-dichlorophenolindophenol, we observed a
      catalytically independent loss of activity. By varying the incubation time for
      the enzyme prior to reaction initiation, we measured an inactivation rate of 0.22
      min(-1). We hypothesized that either an active BMR dimer dissociates to an
      inactive monomer or BMR undergoes denaturation. We were not able to trap or
      destabilize a dimer, and BMR inactivation proved to be irreversible. Addition of
      excess FMN only slightly decreased the rate of inactivation from 0.22 to 0.13
      min(-1), indicating inactivation likely does not reflect loss of flavin. When
      inactivation rates as a function of temperature were fit to the Arrhenius
      equation, the energy required to inactivate BMR was 9.9 kcal mol(-1)--equivalent
      to a few hydrogen bonds. The potential instability of BMR under certain
      conditions raises concerns for the use of BMR as a model or surrogate P450
      reductase in other systems.

PMID- 15950924
TI  - Inhibitor studies on non-photochemical plastoquinone reduction and H(2)
      photoproduction in Chlamydomonas reinhardtii.
AB  - In the absence of PSII, non-photochemical reduction of plastoquinones (PQs)
      occurs following NADH or NADPH addition in thylakoid membranes of the green alga
      Chlamydomonas reinhardtii. The nature of the enzyme involved in this reaction has
      been investigated in vitro by measuring chlorophyll fluorescence increase in
      anoxia and light-dependent O(2) uptake in the presence of methyl viologen. Based
      on the insensitivity of these reactions to rotenone, a type-I NADH dehydrogenase
      (NDH-1) inhibitor, and their sensitivity to flavoenzyme inhibitors and thiol
      blocking agents, we conclude to the involvement of a type-II NADH dehydrogenase
      (NDH-2) in PQ reduction. Intact Chlamydomonas cells placed in anoxia have the
      property to produce H(2) in the light by a Fe-hydrogenase which uses reduced
      ferredoxin as an electron donor. H(2) production also occurs in the absence of
      PSII thanks to the existence of a non-photochemical pathway of PQ reduction. From
      inhibitors effects, we suggest the involvement of a plastidial NDH-2 in PSII
      independent H(2) production in Chlamydomonas. These results are discussed in
      relation to the absence of ndh genes in Chlamydomonas plastid genome and to the
      existence of 7 ORFs homologous to type-II NDHs in its nuclear genome.

PMID- 15950925
TI  - Irreversible photoinhibition of photosystem II is caused by exposure of
      Synechocystis cells to strong light for a prolonged period.
AB  - Irreversible photoinhibition of photosystem II (PSII) occurred when Synechocystis
      sp. PCC 6803 cells were exposed to very strong light for a prolonged period. When
      wild-type cells were illuminated at 20 degrees C for 2 h with light at an
      intensity of 2,500 micromol photons m(-2) s(-1), the oxygen-evolving activity of
      PSII was almost entirely and irreversibly lost, whereas the photochemical
      reaction center in PSII was inactivated only reversibly. The extent of
      irreversible photoinhibition was enhanced at lower temperatures and by the
      genetically engineered rigidification of membrane lipids. Western and Northern
      blotting demonstrated that, after cells had undergone irreversible
      photoinhibition, the precursor to D1 protein in PSII was synthesized but not
      processed properly. These observations may suggest that exposure of Synechocystis
      cells to strong light results in the irreversible photoinhibition of the oxygen
      evolving activity of PSII via impairment of the processing of pre-D1 and that
      this effect of strong light is enhanced by the rigidification of membrane lipids.

PMID- 15950926
TI  - Extinction coefficients of cytochromes b559 and c550 of Thermosynechococcus
      elongatus and Cyt b559/PS II stoichiometry of higher plants.
AB  - "Reduced minus oxidized" difference extinction coefficients Deltavarepsilon in
      the alpha-bands of Cyt b559 and Cyt c550 were determined by using functionally
      and structurally well-characterized PS II core complexes from the thermophilic
      cyanobacterium Thermosynechococcus elongatus. Values of 25.1+/-1.0 mM(-1) cm(-1)
      and 27.0+/-1.0 mM(-1) cm(-1) were obtained for Cyt b559 and Cyt c550,
      respectively. Anaerobic redox titrations covering the wide range from -250 up to
      +450 mV revealed that the heme groups of both Cyt b559 and Cyt c550 exhibit
      homogenous redox properties in the sample preparation used, with E(m) values at
      pH 6.5 of 244+/-11 mV and -94+/-21 mV, respectively. No HP form of Cyt b559 could
      be detected. Experiments performed on PS II membrane fragments of higher plants
      where the content of the high potential form of Cyt b559 was varied by special
      treatments (pH, heat) have shown that the alpha-band extinction of Cyt b559 does
      not depend on the redox form of the heme group. Based on the results of this
      study the Cyt b559/PSII stoichiometry is inferred to be 1:1 not only in
      thermophilic cyanobacteria as known from the crystal structure but also in PSII
      of plants. Possible interrelationships between the structure of the Q(B) site and
      the microenvironment of the heme group of Cyt b559 are discussed.

PMID- 15950927
TI  - Coherent phase microscopy in cell biology: visualization of metabolic states.
AB  - Visualization of functional properties of individual cells and intracellular
      organelles still remains an experimental challenge in cell biology. The coherent
      phase microscopy (CPM) provides a convenient and non-invasive tool for imaging
      cells and intracellular organelles. In this work, we report results of
      statistical analysis of CPM images of cyanobacterial cells (Synechocystis sp. PCC
      6803) and spores (Bacillus licheniformis). It has been shown that CPM images of
      cyanobacterial cells and spores are sensitive to variations of their metabolic
      states. We found a correlation between one of optical parameters of the CPM image
      ('phase thicknesses' Deltah) and cell energization. It was demonstrated that the
      phase thickness Deltah decreased after cell treatment with the uncoupler CCCP or
      inhibitors of electron transport (KCN or DCMU). Statistical analysis of
      distributions of parameter Deltah and cell diameter d demonstrated that a
      decrease in the phase thickness Deltah could not be attributed entirely to a
      decrease in geometrical sizes of cells. This finding demonstrates that the CPM
      technique may be a convenient tool for fast and non-invasive diagnosis of
      metabolic states of individual cells and intracellular organelles.

PMID- 15950928
TI  - Structure and thermal history dependent phase behavior of hydrated synthetic
      sphingomyelin analogue: 1,2-dimyristamido-1,2-deoxyphosphatidylcholine.
AB  - The physical properties of hydrated multilamellar sample of 1,2-dimyristamido-1,2
      deoxyphosphatidylcholine (DDPC) were investigated by means of differential
      scanning calorimetry (DSC), static X-ray diffraction, and simultaneous DSC and X
      ray diffraction. The DDPC is a synthetic sphingomyelin analogue and has two amide
      bonds in its hydrophobic parts. This paper reports on metastable phase behavior
      of the hydrated DDPC sample. By cooling from a chain-melted state at the rates of
      greater than 4 degrees C min(-1), hydrated DDPC bilayers form a metastable gel
      phase. In the gel phase, the hydrophobic chains are tilted with respect to the
      bilayer normal, as like the gel phase of glycero-phosphatidylcholines. By
      heating, the metastable gel phase is transformed in to a stable phase associated
      with an exothermic heat event at 18.3 degrees C (DeltaH=14.6 kJ mol(-1)) and then
      the stable phase is transformed into a liquid-crystalline phase at 25.6 degrees C
      (DeltaH=42 kJ mol(-1)). The incubation at 17 degrees C for more than 1 h also
      induces the formation of the stable phase. In the stable phase, the hydrophobic
      chains are packed into highly ordered crystal-like structure. However, the X-ray
      diffraction pattern of the stable phase suggested that the entire DDPC molecules
      do not form a two-dimensional molecular ordered lattice, differing from normal
      subgel phase of glycero-phosphatidylcholines. The structure and phase behavior of
      DDPC revealed by the present study are discussed from the viewpoint of hydrogen
      bonds.

PMID- 15950929
TI  - Unusual protein behavior illustrated with silk fibroin.
AB  - We investigated the interaction between phospholipid membranes and silk fibroin
      recovered from the posterior silk gland of the silkworm. Observations of the
      planar lipid bilayer membrane and electron microscopic observations of liposomes
      showed that newly constructed silk fibroin, existing in the form of filaments,
      quickly penetrates phospholipid membranes without bursting them.

PMID- 15950930
TI  - World assumptions and the role of trauma in borderline personality disorder.
AB  - The present study tested whether borderline personality disorder (BPD) is
      characterized by specific worldviews as hypothesized by cognitive models, using
      Janoff-Bulman's [(1989) Social Cognition, 7, 113-136] world assumptive model of
      negative effects of trauma. A second aim of this study was to investigate the
      role of trauma in the content of worldviews of BPD patients. Fifteen BPD
      patients, 14 patients with Cluster C personality disorders (PD), 19 patients with
      axis-I psychopathology and 21 non-patients filled out the World Assumptions
      Scale, the Personality Disorder Belief Questionnaire, a childhood trauma
      checklist (assessing physical, emotional and sexual abuse) and the BPD Checklist
      (severity of BPD psychopathology). BPD patients appear to view the world as
      malevolent and perceive less luck independent of trauma but dependent of BPD
      psychopathology. Furthermore, BPD patients have low self-worth and persist in
      specific beliefs independent of trauma or severity of BPD psychopathology.
      Pretzer's theory of BPD can be largely supported through Janoff-Bulman's world
      assumptive model. World assumptions of BPD patients can better be explained by
      the severity of BPD psychopathology than by the presence of trauma.

PMID- 15950931
TI  - Evaluations of emotional noninterpersonal situations by patients with borderline
      personality disorder.
AB  - According to cognitive models of borderline personality disorder (BPD), an
      important cause for the instability of patients with BPD is dichotomous thinking
      (DT). Object-relation theories assume that the similar phenomenon of splitting is
      central in BPD. Previous studies focusing on interpersonal situations found
      support for DT being prominent in BPD. The aim of this study was to investigate
      whether patients with BPD also make use of dichotomous and schema-specific
      evaluations in noninterpersonal situations. An experiment was designed in which a
      frustrating and rewarding situation was induced by computer games that subjects
      had to play. Participants evaluated both themselves and the games. Patients with
      BPD (n=24) were characterized by somewhat more extreme game evaluations in the
      emotionally negative situations than normal controls (n=25), participants with a
      cluster C (n=10) or an anti-social personality disorder (ASPD) (n=16). Patients
      with BPD appeared to be characterized best by a general negative evaluative
      style, more than by DT or splitting. ASPD participants showed a positivity bias
      in both conditions.

PMID- 15950932
TI  - Electron capture dissociation mass spectrometry in characterization of post
      translational modifications.
AB  - Electron capture dissociation (ECD) represents a significant advance in tandem
      mass spectrometry for the identification and characterization of post
      translational modifications (PTMs) of polypeptides. In comparison with the
      conventional fragmentation techniques, such as collisionally induced dissociation
      and infrared multi-photon dissociation, ECD provides more extensive sequence
      fragments, while allowing the labile modifications to remain intact during
      backbone fragmentation. This unique attribute offers ECD as an attractive
      alternative for detection and localization of PTMs. The success and rapid
      adoption of ECD recently led to the culmination of The 1st International Uppsala
      Symposium on Electron Capture Dissociation of Biomolecules and Related Phenomena
      (October 19-22, 2003, Stockholm, Sweden). Herein, we present a general overview
      of the ECD technique as well as selected applications in characterization of post
      translationally modified polypeptides.

PMID- 15950933
TI  - Antagonist and agonist binding models of the human gonadotropin-releasing hormone
      receptor.
AB  - G-protein-coupled receptors (GPCRs) constitute one of the most important classes
      of drug targets. Since the first high-resolution structure of a GPCR was
      determined by Palczewski and co-workers [K. Palczewski, T. Kumasaka, T. Hori,
      C.A. Behnke, H. Motoshima, B.A. Fox, I. Le Trong, D.C. Teller, T. Okada, R.E.
      Stenkamp, M. Yamamoto, M. Miyano, Crystal structure of rhodopsin: a G-protein
      coupled receptor, Science 289 (2000) 739-745], development of in silico models of
      rhodopsin-like GPCRs could be rationally founded. In this work, we present a
      model of the human gonadotropin-releasing hormone receptor based on the rhodopsin
      structure. The transmembrane helices are modeled by homology, while the extra-
      and intra-cellular loops are modeled in such a way that experimentally determined
      interactions and microdomains (e.g., hydrophobic cores) are retained. We conclude
      that specifically tailored models, compared to more automatic approaches, have
      the benefit that known interactions are easily introduced early in the homology
      modeling. Furthermore, tailored models, although more tedious to construct, are
      better suited for drug lead finding and for compound optimization. To test the
      stability of the receptor, we performed a 1 ns molecular dynamics simulation.
      Moreover, we docked two agonists (native GnRH and Triptorelin, [dTrp(6)]-GnRH)
      and two antagonists (Cetrorelix, dNal(1)-dCpa(2)-dPal(3)-Ser(4)-Tyr(5)-dCit(6)
      Leu(7)-Arg(8)-Pro(9)-dAla(10)), and the covalently constrained dicyclic
      decapeptide dicyclo(1,1'-5/4-10)[Ac-Glu(1)(Gly(1)')-dCpa(2)-dTrp(3)-Asp(4)-dbu(5)
      dNal(6)-Leu(7)-Arg(8)-Pro(9)-dpr(10)-NH(2)] into the putative receptor binding
      site. The docked ligand conformations result in ligand-receptor interactions that
      are generally in good agreement with site-directed mutagenesis and ligand-binding
      studies presented in the literature. Our results indicate that the binding
      conformation of the antagonists differs from that of the agonists. This
      difference can be linked to the activation or inhibition of the receptor.

PMID- 15950934
TI  - beta-Microseminoprotein binds CRISP-3 in human seminal plasma.
AB  - beta-Microseminoprotein (MSP) and cysteine-rich secretory protein 3 (CRISP-3) are
      abundant constituents of human seminal plasma. Immunoprecipitation and gel
      filtration of seminal plasma proteins combined with examination of the proteins
      in their pure form showed that MSP and CRISP-3 form stable, non-covalent
      complexes. CRISP-3 binds MSP with very high affinity, as evidenced by surface
      plasmon resonance. Due to far higher abundance of MSP in prostatic fluid, it
      manifests large overcapacity for CRISP-3 binding. Structural similarity with an
      MSP-binding protein from blood plasma suggests that CRISP-3 binds MSP through its
      aminoterminal SCP-domain.

PMID- 15950935
TI  - Neuroprotection by iron chelator against proteasome inhibitor-induced nigral
      degeneration.
AB  - The cause of the neurodegenerative process in Parkinson's disease (PD) remains
      unclear, but evidence suggests that failure of the ubiquitin-proteasome system
      may play a major role in the pathogenesis of the disease. Iron is believed to be
      a key contributor to PD pathology by inducing aggregation of alpha-synuclein and
      by generating oxidative stress. Our present studies have shown that micro
      injection of the proteasome inhibitor lactacystin into the substantia nigra (SN)
      of C57BL/6 mice causes significant loss of dopaminergic cells and induces
      intracellular inclusion body formation. We have also found that co-injection of
      the iron chelator desferrioxamine not only attenuates the lactacystin-induced
      dopamine neuron loss, but also reduces the presence of ubiquitin-positive
      intracellular inclusions in the SN, whereas use of iron-deficient diet has no
      such protective effects. These results may support that iron plays a key role in
      proteasome inhibitor-induced nigral pathology and that reducing iron reactivity
      may prevent dopaminergic neuron degeneration and reduce abnormal protein
      aggregation.

PMID- 15950936
TI  - Chemokine receptor CCR7 is expressed in muscle fibers in juvenile
      dermatomyositis.
AB  - To better elucidate the pathogenesis of lymphocyte recruitment of memory CD4(+) T
      cells in inflammatory myopathies, we studied the expression of CCR5 and CCR7 on
      CD4 memory T cells in muscle tissue from 11 patients with juvenile
      dermatomyositis, six adult patients with polymyositis, two patients with Duchenne
      muscular dystrophy, and two patients with spinal muscular atrophy. A prevalent
      infiltration of CCR5(+) effector CD4 T memory cells is observed in inflammatory
      myopathies. Moreover, we found a strong expression of CCR7 in perifascicular
      atrophic and in degenerating/regenerating muscle fibers in juvenile
      dermatomyositis (JDM) but not in fibers from adult polymyositis and Duchenne
      muscular dystrophy. The selective expression of CCR7 in JDM may open new
      perspectives in the understanding of the pathogenesis of inflammatory myopathies,
      offering a new tool for the differential diagnosis of these disorders.

PMID- 15950937
TI  - Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host
      immune responses.
AB  - Shigella effectors injected into the host cell via the type III secretion system
      are involved in various aspects of infection. Here, we show that one of the
      effectors, IpaH9.8, plays a role in modulating inflammatory responses to Shigella
      infection. In murine lung infection model, DeltaipaH9.8 mutant caused more severe
      inflammatory responses with increased pro-inflammatory cytokine production levels
      than did wild-type Shigella, which resulted in a 30-fold decrease in bacterial
      colonization. Binding assays revealed that IpaH9.8 has a specific affinity to
      U2AF(35), a mammalian splicing factor, which interferes with U2AF(35)-dependent
      splicing as assayed for IgM pre-mRNA. Reducing the U2AF(35) level in HeLa cells
      and infecting HeLa cells with wild-type caused a decrease in the expression of
      the il-8, RANTES, GM-CSF, and il-1beta genes as examined by RT-PCR. The results
      indicate that IpaH9.8 plays a role in Shigella infection to optimize the host
      inflammatory responses, thus facilitating bacterial colonization within the host
      epithelial cells.

PMID- 15950938
TI  - The rapid onset of elasticity during the assembly of the bacterial cell-division
      protein FtsZ.
AB  - FtsZ, a prokaryotic homolog of eukaryotic tubulin, is a major constituent of the
      bacterial Z-ring, which contracts the cell wall during cell division. Because the
      mechanical properties of FtsZ are unknown, its function in the maintenance and
      constriction of the Z-ring is not well understood. Here, quantitative rheometry
      shows that, at physiological concentrations, FtsZ filaments form, extremely
      rapidly, highly elastic networks within physiological time scales ( approximately
      minutes), much faster than other major dynamic cytoskeletal filaments, including
      microtubule, actin, and vimentin in eukaryotes. FtsZ networks display a
      relatively low viscosity and a high resilience against shear stresses, as well as
      an elasticity that depends weakly on concentration, G approximately C(0.57), a
      power-law dependence consistent with crosslinked flexible filaments. Calcium,
      whose intracellular concentration increases during bacterial division, further
      enhances the elasticity of FtsZ networks through filament bundling, an effect
      that occurs in the presence of GTP, not GDP. These studies suggest that FtsZ
      filaments have the toughness to provide strong mechanical support for the
      maintenance and circumferential constriction of the bacterial Z-ring.

PMID- 15950940
TI  - Diverse NO reduction by Halomonas halodenitrificans nitric oxide reductase.
AB  - Reduction of the four Fe centers is not required to initiate the reaction of the
      Halomonas halodenitrificans nitric oxide reductase (NOR) based on the facts that
      NOR in the form that ferric heme b(3) and non-heme iron (Fe(B)) are not bridged
      and/or the interaction between them is weakened and reversibly binds NO
      molecules, and that NOR in the form that only heme b(3) is oxidized reacts with
      NO molecules.

PMID- 15950939
TI  - PKA-mediated protein phosphorylation protects ezrin from calpain I cleavage.
AB  - Ezrin is localized to the apical membrane of parietal cells and couples the cAMP
      dependent protein kinase (PKA) activation cascade to the regulated HCl secretion
      in gastric parietal cells. Our recent studies demonstrate the functional
      relevance of PKA-mediated phosphorylation of ezrin in parietal cell secretion [R.
      Zhou, X. Cao, C. Watson, Y. Miao, Z. Guo, J.G. Forte, X. Yao, Characterization of
      protein kinase A-mediated phosphorylation of ezrin in gastric parietal cell
      activation, J. Biol. Chem. 278 (2003) 35651]. Here we show that activation of PKA
      protects ezrin from calpain I-mediated proteolysis without alteration of calpain
      I activation and fodrin breakdown. To determine whether phosphorylation of Ser66
      by PKA affects the insensitivity to the calpain I-mediated cleavage, recombinant
      proteins of ezrin, both wild type and S66A/D mutants, were incubated with the
      purified calpain I. Indeed, phosphorylation-like S66D mutant ezrin is resistant
      to calpain I-mediated proteolysis while wild type and S66A mutant were sensitive.
      In fact, expression of phosphorylation-like S66D, but not S66A, mutant in
      parietal cells confers its resistance to calpain I-mediated proteolysis. Taken
      together, these results indicate that phosphorylation of ezrin by PKA modulates
      its sensitivity to calpain I cleavage.

PMID- 15950941
TI  - IL-20, an anti-angiogenic cytokine that inhibits COX-2 expression.
AB  - COX-2 overexpression and subsequent PGE(2) production are frequently associated
      with non-small cell lung cancer and are implicated in tumor-mediated
      angiogenesis. Here, we report for the first time that IL-20 downregulates COX-2
      and PGE(2) in human bronchial epithelial and endothelial cells. Flow cytometry
      analysis suggests that IL-20-dependent inhibition of COX-2/PGE(2) occurs through
      the IL-22R1/IL-20R2 dimers. In addition, we report that IL-20 exerts anti
      angiogenic effects, inhibiting experimental angiogenesis. IL-20-mediated
      inhibition of PMA-induced angiogenesis occurs through the COX-2 regulatory
      pathway. Altogether our findings revealed that IL-20 is a negative modulator of
      COX-2/PGE(2) and inhibits angiogenesis.

PMID- 15950942
TI  - The PPAR-gamma activator, Rosiglitazone, inhibits actin polymerisation in
      monocytes: involvement of Akt and intracellular calcium.
AB  - Monocyte hyperactivation as seen in diabetes results in increased cytoskeletal
      rigidity and reduced cell deformability leading to microchannel occlusions and
      microvascular complications. The thiazolidinediones (TZDs) are PPAR-gamma
      agonists that have been reported to exert beneficial non-metabolic effects on the
      vasculature. This study demonstrates that the TZD, Rosiglitazone, significantly
      reduces f-MLP-induced actin polymerisation in human monocytic cells (p < 0.05).
      Two of the key signalling processes known to be involved in the regulation of
      cytoskeletal remodelling were investigated: PI(3)K-dependent Akt phosphorylation
      and intracellular calcium concentration [Ca(2+)](i). The PI(3)K inhibitor,
      Wortmannin, ameliorated f-MLP-induced actin polymerisation (p < 0.05), while the
      Ca(2+) sequestration inhibitor, thapsigargin, induced actin depolymerisation (p <
      0.05), confirming the involvement of both processes in cytoskeletal remodelling.
      Rosiglitazone significantly reduced f-MLP activation of Akt (p < 0.05), and
      significantly increased [Ca(2+)](i) in both resting and f-MLP-stimulated cells (p
      < 0.05). Therefore, Rosiglitazone interacts with signalling events downstream of
      occupancy of the f-MLP receptor, to modulate cytoskeletal remodelling in a PPAR
      gamma-independent manner. To our knowledge, these results are the first to
      present evidence that a PPAR-gamma agonist can modulate actin remodelling in
      monocytes, and may therefore be protective against microvascular damage in
      diabetes.

PMID- 15950943
TI  - Cell-autonomous PrP-Doppel interaction regulates apoptosis in PrP gene-deficient
      neuronal cells.
AB  - The Prnd-encoded prion protein (PrP)-like protein, Doppel (Dpl), is a homologue
      of Prnp-encoded PrP, and is N-glycosylated protein with
      glycosylphosphatidylinositol anchor like PrP. Recently, ectopic expressions of
      Prnp/Prnd chimeric mRNAs have been identified as the cause of late-onset ataxia
      observed in several lines of Prnp-knockout mice such as ZrchII, Ngsk, Rcm0, and
      Rikn mice. However, it remains unclear whether the toxic effect of Dpl expression
      is a cell-autonomous mechanism but rather reflect a systemic process of
      heterogeneous cell population in the brain. In this study, the cell-autonomous
      role of Dpl was estimated by investigating PrP-deficient cells (HpL3-4)-the SV40
      large T-antigen immortalized and Rikn Prnp(-/-) mice-derived neuronal cell line
      expressing Prnp/Prnd chimeric mRNAs. The reverse transcription polymerase chain
      reaction revealed that serum deprivation did not increase Prnp/Prnd chimeric
      mRNAs, which in fact was translated into a small amount of Dpl in HpL3-4 cells,
      whereas serum deprivation induced apoptotic cell death of HpL3-4 cells. Dpl
      overexpression enhanced apoptotic cell death, whereas the toxic effect of Dpl on
      apoptotic cell death was neutralized by PrP expression. These results indicate
      that Dpl elicited dose-dependently toxic effects on PrP-deficient cells without
      affecting on PrP-expressing cells, suggesting that the PrP-Dpl interaction can
      regulate cell death in a cell-autonomous manner.

PMID- 15950944
TI  - Chk2 regulates transcription-independent p53-mediated apoptosis in response to
      DNA damage.
AB  - The tumor suppressor protein p53 plays a central role in the induction of
      apoptosis in response to genotoxic stress. The protein kinase Chk2 is an
      important regulator of p53 function in mammalian cells exposed to ionizing
      radiation (IR). Cells derived from Chk2-deficient mice are resistant to the
      induction of apoptosis by IR, and this resistance has been thought to be a result
      of the defective transcriptional activation of p53 target genes. It was recently
      shown, however, that p53 itself and histone H1.2 translocate to mitochondria and
      thereby induces apoptosis in a transcription-independent manner in response to
      IR. We have now examined whether Chk2 also regulates the transcription
      independent induction of apoptosis by p53 and histone H1.2. The reduced ability
      of IR to induce p53 stabilization in Chk2-deficient thymocytes was associated
      with a marked impairment of p53 and histone H1 translocation to mitochondria.
      These results suggest that Chk2 regulates the transcription-independent mechanism
      of p53-mediated apoptosis by inducing stabilization of p53 in response to IR.

PMID- 15950945
TI  - alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic
      wound healing in patients undergoing hyperbaric oxygen therapy.
AB  - Hyperbaric oxygen (HBO) therapy is successfully used for the treatment of a
      variety of conditions. However, prolonged exposure to high concentrations of
      oxygen induces production of reactive oxygen species, causing damage to the
      cells. Thus, antioxidant supplementation has been proposed as an adjuvant to
      attenuate such deleterious secondary effects. We evaluated the effects of alpha
      lipoic acid (LA) in patients affected by chronic wounds undergoing HBO treatment.
      LA supplementation efficiently reduces both the lipid and DNA oxidation induced
      by oxygen exposure. LA exerted its antioxidant activity by directly interacting
      with free radicals or by recycling vitamin E. An inhibitory effect of LA on the
      pro-inflammatory cytokine interleukin-6 was observed. Taken together, we
      demonstrated an adjuvant effect of LA in HBO therapy used for impaired wound
      healing treatment. We propose that LA may be used to further promote the
      beneficial effects of HBO therapy.

PMID- 15950946
TI  - Calmodulin interaction with peptides from G-protein coupled receptors measured
      with S-Tag labeling.
AB  - We have developed a quantitative assay of calmodulin (CaM) binding to S-Tag
      labeled peptides derived from G-protein coupled receptor (GPCR) sequences. CaM
      binding of peptides derived from the third intracellular loop (i3) of mu opioid
      receptor (MOR) was confirmed and the CaM-binding motif refined. A MORi3 peptide
      with a Lys > Ala substitution--shown to reduce CaM-binding of intact MOR--bound
      fivefold less avidly than the wild-type peptide. Screening peptides derived from
      i3 loops of other GPCR families confirmed 5HT1A, and identified muscarinic
      receptor 3, and melanocortin receptor 1, as proteins carrying CaM-binding
      domains. The use of S-Tag labeling can serve for rapid screening of putative CaM
      binding domains in GPCRs.

PMID- 15950947
TI  - Mechanisms and significance of bifunctional NK4 in cancer treatment.
AB  - Based on the background that hepatocyte growth factor (HGF) and c-Met/HGF
      receptor tyrosine kinase play a definite role in tumor invasion and metastasis,
      NK4, four-kringles containing intramolecular fragment of HGF, was isolated as a
      competitive antagonist for the HGF-c-Met system. Independent of its HGF
      antagonist action, NK4 inhibited angiogenesis induced by vascular endothelial
      cell growth factor and basic fibroblast growth factor, as well as HGF, indicating
      that NK4 is a bifunctional molecule that acts as an HGF-antagonist and
      angiogenesis inhibitor. Interestingly, kringle domains in distinct types of
      proteins, e.g., plasminogen, prothrombin, plasminogen activators,
      apolipoprotein(a), and HGF, share angioinhibitory actions. In experimental models
      of distinct types of cancers, NK4 protein administration or NK4 gene therapy
      inhibited tumor invasion, metastasis, and angiogenesis-dependent tumor growth.
      Cancer treatment with NK4 may prove to suppress malignant tumors to be 'static'
      in both tumor growth and spreading, as based on biological characteristics of
      malignant tumors.

PMID- 15950948
TI  - The interaction of methylphenidate and benztropine with the dopamine transporter
      is different than other substrates and ligands.
AB  - A substantial body of evidence suggests that the dopamine transporter (DAT) is
      the principal site for cocaine-induced reward and euphoria. Interactions between
      the DAT and its substrates and ligands may therefore be of clinical relevance.
      The pharmacological characteristics of DAT compounds were compared in wild type
      (WT) and mutant DATs. The DAT mutants chosen for study were those with reduced
      binding and uptake activities (aspartic acid 79 mutated to alanine, termed D79A),
      reduced binding but normal uptake (tyrosine 251 mutated to alanine, termed Y251A;
      tyrosine 273 mutated to alanine, termed, Y273A), and normal binding but reduced
      uptake (a double mutation: serines 356 and 359 mutated to alanine, termed
      S356,359A). The WT and mutant DATs were transfected into COS-7 cells, and their
      pharmacological activities were examined 3 days later. Different patterns of
      pharmacological activity emerged. GBR 12909, cocaine, and mazindol each showed
      reduced affinity for the Y251A and the Y273A mutants, but their affinity for the
      S356,359A mutant was similar to that of the WT DAT. d-Amphetamine, MPP+, and
      dopamine each showed reduced affinity for the S356,359A mutant. Benztropine and
      methylphenidate had a different effect. Relative to the WT DAT, they both showed
      reduced affinity for the S356,359A mutant when displacing radioactive
      carboxyfluorotropane (CFT) binding, but similar affinity when inhibiting
      radioactive dopamine uptake. These results indicate that methylphenidate and
      benztropine may interact with the DAT in a different fashion then other
      substrates and ligands.

PMID- 15950949
TI  - Depletion of RLIP76 sensitizes lung cancer cells to doxorubicin.
AB  - Ral-interacting protein (RLIP76) (RALBP1) is an anti-apoptotic non-ABC
      glutathione (GSH)-conjugate transporter involved in receptor-ligand endocytosis,
      as well as in multispecific drug transport and resistance. Partial inhibition of
      RLIP76 using antibodies in the absence of chemotherapy drug causes apoptosis in
      multiple small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)
      cell lines and in the presence of doxorubicin (DOX), marked synergy is observed.
      These findings indicated that RLIP76 should be a good target for cancer cell
      killing; its down-regulation would promote apoptosis through both drug-dependent
      and drug-independent effects. To examine the effect of complete and specific
      RLIP76 depletion on apoptosis, we tested the effects of RLIP76 siRNA in a number
      of lung cancer cell lines. Growth inhibition and apoptosis was observed in all
      cases upon RLIP76 depletion. Consistent with these findings, augmenting cellular
      RLIP76 through transfection or liposomal protein delivery conferred resistance to
      apoptosis mediated by either DOX or 4-hydroxynonenal (4-HNE). Taken together, our
      results show that RLIP76 is rational and promising new target for lung cancer
      therapy.

PMID- 15950950
TI  - Cytosine arabinoside affects multiple cellular factors and induces drug
      resistance in human lymphoid cells.
AB  - Continuous in vitro cultivation of human lymphoid H9 cells in the presence of
      0.5microM arabinosyl-cytosine (araC) resulted in cell variant, H9-araC cells,
      that was >600-fold resistant to the drug and cross resistant to its analogs and
      other unrelated nucleosides, e.g. dideoxycytidine (5-fold), thiacytidine (2
      fold), 2-fluoro-adenine arabinoside (8.3-fold), and 2-chloro-deoxyadenosine (2.1
      fold). Compared to the parental cell line, the resistant cells accumulated <1%
      araCTP, and had reduced deoxycytidine kinase (dCK) activity (31.4%) and
      equilibrative nucleoside transporter 1 (ENT1) protein. The expression of the dCK
      gene in araC resistant cells was reduced to 60% of H9 cells, which correlated
      with lower dCK protein and activity. Whereas, there was no difference in the
      expression of ENT1 mRNA between the cell lines, ENT1 protein content was much
      lower in the resistant cells than in H9 cells. The concentrative nucleoside
      transporter (CNT3) was slightly increased in H9-araC cells, but CNT2, and MDR1
      remained unaffected. Although a definitive correlation remains to be established,
      the amount of Sp1 protein, a transcription factor, that regulates the expressions
      of dCK, nucleoside transporters and other cellular proteins, was found reduced in
      H9-araC cells. Like ENT1, the Sp1 mRNA levels remained unaffected in H9-araC
      whereas protein contents were reduced. These observations are indicative of
      differences in the production and/or turnover of ENT1 and Sp1 proteins in H9-araC
      cells. Since nucleoside transporters and dCK play an important role in the
      activity of potential antiviral and anticancer deoxynucleoside analogs,
      understanding of their regulation is important. These studies show that the
      exposure of cells to araC, in vitro, is capable of simultaneously affecting more
      than one target site to confer resistance. The importance of this observation in
      the clinical use of araC remains to be determined.

PMID- 15950951
TI  - Evaluation of the neuronal apoptotic pathways involved in cytoskeletal disruption
      induced apoptosis.
AB  - The cytoskeleton is critical to neuronal functioning and survival. Cytoskeletal
      alterations are involved in several neurodegenerative diseases such as
      Alzheimer's and Parkinson's diseases. We studied the possible pathways involved
      in colchicine-induced apoptosis in cerebellar granule neurons (CGNs). Although
      colchicine evoked an increase in caspase-3, caspase-6 and caspase-9 activation,
      selective caspase inhibitors did not attenuate apoptosis. Inhibitors of other
      cysteine proteases such as PD150606 (a calpain-specific inhibitor), Z-Phe-Ala
      fluoromethyl ketone (a cathepsins-inhibitors) and N(alpha)-p-tosyl-l-lysine
      chloromethyl ketone (serine-proteases inhibitor) also had no effect on cell
      death/apoptosis induced by colchicine. However, BAPTA-AM 10 microM (intracellular
      calcium chelator) prevented apoptosis mediated by cytoskeletal alteration. These
      data indicate that calcium modulates colchicine-induced apoptosis in CGNs. PARP-1
      inhibitors did not prevent apoptosis mediated by colchicine. Finally, colchicine
      induced apoptosis in CGNs was attenuated by kenpaullone, a cdk5 inhibitor.
      Kenpaullone and indirubin also prevented cdk5/p25 activation mediated by
      colchicine. These findings indicate that cytoskeletal alteration can compromise
      cdk5 activation, regulating p25 formation and suggest that cdk5 inhibitors
      attenuate apoptosis mediated by cytoskeletal alteration. The present data
      indicate the potential therapeutic value of drugs that prevent the formation of
      p25 for the treatment of neurodegenerative disorders.

PMID- 15950952
TI  - HDAC inhibition prevents NF-kappa B activation by suppressing proteasome
      activity: down-regulation of proteasome subunit expression stabilizes I kappa B
      alpha.
AB  - The short chain fatty acid (SCFA) butyrate (BA) and other histone deacetylase
      (HDAC) inhibitors can rapidly induce cell cycle arrest and differentation of
      colon cancer cell lines. We found that butyrate and the specific HDAC inhibitor
      trichostatin A (TSA) can reprogram the NF-(kappa)B response in colon cancer
      cells. Specifically, TNF-alpha activation is suppressed in butyrate
      differentiated cells, whereas IL-1beta activation is largely unaffected. To gain
      insight into the relationship between butyrate-induced differentiation and NF
      (kappa)B regulation, we determined the impact of butyrate on proteasome activity
      and subunit expression. Interestingly, butyrate and TSA reduced the cellular
      proteasome activity in colon cancer cell lines. The drop in proteasome activity
      results from the reduced expression of the catalytic beta-type subunits of the
      proteasome at both the protein and mRNA level. The selective impact of HDAC
      inhibitors on TNF-alpha-induced NF-(kappa)B activation appears to relate to the
      fact that the TNF-alpha-induced activation of NF-(kappa)B is mediated by the
      proteasome, whereas NF-kappaB activation by IL-1beta is largely proteasome
      independent. These findings indicate that cellular differentation status and/or
      proliferative capacity can significantly impact proteasome activity and
      selectively alter NF-(kappa)B responses in colon cancer cells. This information
      may be useful for the further development and targeting of HDAC inhibitors as
      anti-neoplastic and anti-inflammatory agents.

PMID- 15950953
TI  - Role of medullary excitatory amino acid receptors in mediating the 10-Hz rhythm
      in sympathetic nerve discharge of cats.
AB  - We tested the hypothesis that excitatory amino acid (EAA)-mediated transmission
      plays a role in generating the 10-Hz rhythm in sympathetic nerve discharge (SND)
      of baroreceptor-denervated, urethane-anesthetized cats. Microinjection of either
      an N-methyl-d-aspartate (NMDA) or non-NMDA receptor antagonist into any one of
      three medullary regions (lateral tegmental field, rostral, or caudal
      ventrolateral medulla) essentially eliminated the 10-Hz rhythm in inferior
      cardiac SND. We conclude that EAA receptors in the medulla are critical for
      generation of the 10-Hz rhythm.

PMID- 15950954
TI  - Hibernoma of the antero-lateral thigh.
AB  - Hibernoma is a rare benign tumour of brown fat. In most cases it presents as a
      voluminous slow-growing mass in the regions where remnants of brown fat can
      remain in adults. We report a case of a hibernoma on the thigh and present the
      diagnostic and therapeutic elements of this type of tumour, whose differential
      diagnosis of liposarcoma.

PMID- 15950955
TI  - Athelia: case report and review of the literature.
AB  - The absence of nipple-areola complex is a rare entity and is always associated
      with other anomalies. This paper described a case of bilateral athelia without
      other alterations. The atrophy of the dense mesenchyme due to absence of
      parathyroid hormone-related protein produced in epithelium may lead to nipple
      involution. Further cases should be studied to corroborate this theory.

PMID- 15950957
TI  - The reverse auricular flap for the reconstruction of extended defects of the
      lower eyelid.
AB  - The authors present eight cases of lower eyelid reconstruction after extended
      excision of cutaneous carcinomata. To recreate the supporting function of the
      lower eyelid it is necessary to reconstruct a rigid structure, which must replace
      the tarsus and has to be covered by sufficiently thin skin. A condrocutaneous
      helix island flap, based on the frontal branch of the temporal artery, allows us
      to reconstruct both lamellae of the eyelid at the same time. The reverse flow to
      the flap through this vascular pedicle is assured by the anastomotic branches
      from the supratrochlear and supraorbital arteries. Using this flap we have been
      able to recreate morphology and function of the lower eyelid with a good cosmetic
      result in the donor site as well.

PMID- 15950956
TI  - Accelerated wound healing through the incorporation of basic fibroblast growth
      factor-impregnated gelatin microspheres into artificial dermis using a pressure
      induced decubitus ulcer model in genetically diabetic mice.
AB  - The objective of this study was to evaluate the effect of incorporating basic
      fibroblast growth factor (bFGF)-impregnated gelatin microspheres into an
      artificial dermis on impaired wound healing using a pressure-induced decubitus
      ulcer model in genetically diabetic mice. Daily 10 h prolonged pressure at 500
      g/cm2 was loaded for 2 consecutive days over the femoral trochanter tertius of
      mice to produce ischemic necrosis. Five days after completion of the pressure
      load, the necrotic tissues were resected. Then, an artificial dermis
      incorporating bFGF-impregnated gelatin microspheres or bFGF in solution was
      implanted into the wound (n = 5). Mice were sacrificed at 5, 7, and 10 days after
      implantation, and a full-thickness biopsy was taken and stained with hematoxylin
      and eosin for histological analysis. All experimental animals were infected
      because diabetic mice have little tolerance for infection. Seven days after
      implantation, the incorporation of bFGF into the artificial dermis reduced
      infection and accelerated fibroblast proliferation and capillary formation.
      However, the accelerated effects were more significant with the incorporation of
      bFGF-impregnated gelatin microspheres than with free bFGF. We conclude that the
      incorporation of bFGF-impregnated gelatin microspheres into an artificial dermis
      induced tissue regeneration in an artificial dermis in an impaired wound healing
      model.

PMID- 15950958
TI  - Correction of bilateral congenital swan-neck deformity by use of Mitek mini
      anchor: a new technique.
AB  - Congenital swan neck deformity is a rare condition, secondary to congenital
      laxity of the palmar plate of the proximal interphalangeal joint. Here, we
      describe a new surgical method which is based on the palmar plate reinforcement
      using the Mitek mini anchor system (Mitek Surgical Products Inc., Norwood, MA,
      USA). Four fingers of a patient with congenital swan neck deformities were
      corrected with this technique at two stages. First, the anchor was inserted into
      the volar surface of the proximal phalanx. The two sutures of the anchor system
      were then crossed the PIP joint in a V fashion. Two holes, 5mm apart from each
      other, were created through the middle phalanx distal to both insertion points of
      superficial flexor tendon. The suture ends of the anchor were passed through
      these holes from the volar to the dorsal side of the middle phalanx and then
      turned around the edges of the bone to the volar surface. They were tied to each
      other as the PIP joint was stabilised at 20 degrees flexion by use of a K-wire.
      The K-wire was removed 21 days later and a rehabilitation program was then
      initiated. A second operation for the two fingers of the opposite hand was
      performed 2 months after the first operation. No postoperative complications were
      encountered. At 2 years follow-up, the active range of motion was within normal
      limits at PIP and DIP joints of all four fingers without any recurrence of
      hyperextension or hyperflexion. The final result was satisfactory regarding both
      the functional and cosmetic aspects. The Mitek mini anchor offers a practical,
      reliable and functional reconstruction of the volar plate in the management of
      congenital swan neck deformities. We believe that it may also be used for the
      acquired deformities.

PMID- 15950959
TI  - Reconstruction of a wide abdominal defect using an extended groin flap.
AB  - We present reconstruction of a wide anterior abdominal defect measuring 30 x 45
      cm(2), the result of necrotising pancreatitis. After serial debridements and
      reconstruction of the peritoneum using a Prolene mesh support, a delayed extended
      groin flap was transposed. No complications were encountered afterwards. An
      extended groin flap can be used safely to cover a full-thickness defect of the
      abdominal wall encompassing all of the anatomic subunits.

PMID- 15950960
TI  - Exposure to chemokines during maturation modulates antigen presenting cell
      function of mature macrophages.
AB  - Macrophages generated with macrophage-colony stimulating factor (M-CSF) are
      defective in antigen presenting cell (APC) function, although they do express
      major histocompatibility (MHC) class II molecules, numerous accessory molecules,
      and intercellular adhesion molecules. In the present study, we show evidence that
      the acquisition of APC function is influenced significantly by microenvironmental
      condition of development. Macrophages generated from bone marrow progenitor cells
      with M-CSF and interleukin (IL)-6 were defective in APC function as determined by
      their ability to induce anti-CD3 monoclonal antibody (mAb)-primed T cell
      proliferation. Macrophages generated in the presence of some of the CC chemokines
      such as leukotactin-1, macrophage inflammatory protein (MIP)-1alpha, and RANTES
      together with M-CSF and IL-6, however, induced proliferation of anti-CD3 mAb
      primed T cells. Maximum level of APC function was obtained when developing
      macrophages were exposed with the chemokines at the late stage of maturation.
      Enhanced APC function of the macrophages appeared to be correlated with the
      expression of co-stimulatory molecules and the ability to produce cytokines.
      These results suggest that the acquisition of APC function of mature macrophage
      is modulated significantly by the microenvironmental condition during
      development.

PMID- 15950961
TI  - Expression and function of Toll-like receptor on T cells.
AB  - Toll is the founder of a group of pattern recognition receptors, which play a
      critical role in the innate immunity in Drosophila. At least 13 distinct Toll
      like receptors (TLRs), recognising pathogen-associated molecular pattern (PAMPs),
      have now been identified in humans. Most investigations on TLRs have focused on
      cells of the innate system. We report here that naive human T cells expressed
      high levels of cell surface TLR2 after activation by anti-T cell receptor (TCR)
      antibody and interferon-alpha. Activated cells produced elevated levels of
      cytokines in response to the TLR2 ligand, bacterial lipopeptide (BLP).
      Furthermore, CD4(+)CD45RO(+) memory T cells from peripheral blood constitutively
      expressed TLR2 and produced IFNgamma in response to BLP. BLP also markedly
      enhanced the proliferation and IFNgamma production by CD45RO(+) T cells in the
      presence of IL-2 or IL-15. Thus, TLR2 serves as a co-stimulatory receptor for
      antigen-specific T cell development and participates in the maintenance of T cell
      memory. This suggests that pathogens, via their PAMPs, may contribute directly to
      the perpetuation and activation of long term T cell memory in both antigen
      dependent and independent manner.

PMID- 15950962
TI  - Garlic oil and DDB, comprised in a pharmaceutical composition for the treatment
      of patients with viral hepatitis, prevents acute liver injuries potentiated by
      glutathione deficiency in rats.
AB  - A pharmaceutical composition PENNEL comprising garlic oil (GO) and dimethyl-4,4'
      dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDB) as
      ingredients active for phase II enzyme induction and liver protection,
      respectively, has been used as a curative preparation for patients with acute or
      chronic viral hepatitis. In spite of the wide clinical use of PENNEL in Asian and
      Middle Eastern countries, whether GO+DDB treatment synergistically protects the
      liver from injuries potentiated by GSH deficiency compared to the individual
      treatment has not been determined. This study investigated the effects of GO+DDB
      in comparison with each ingredient alone on chemical-induced liver injury
      potentiated by a GSH depleting agent. Rats that had been daily pretreated with
      GO+DDB, GO, DDB, ursodesoxycholic acid or silymarin for 6 days were exposed to
      buthionine sulfoximine (BSO) and then injected with a single dose of CCl4. The
      effects of the agents on acute liver toxicities induced by BSO, CCl4 or BSO+CCl4
      were assessed by blood biochemistry and histopathology. GO+DDB pretreatment
      effectively prevented increases in plasma aminotransferases or lactate
      dehydrogenase activities in rats exposed to BSO+CCl4, compared to GO or DDB
      treatment alone. Whereas BSO potentiated CCl4-induced liver injuries as evidenced
      by elevations in central necrosis, hepatocyte degeneration and inflammation,
      pretreatment with GO+DDB abrogated BSO+CCl4-induced liver injuries more
      efficaciously than did that with GO or DDB. The hepatoprotective effect of GO+DDB
      was superior to that of ursodesoxycholic acid or silymarin. Also, blood
      biochemistry indicated that GO+DDB pretreatment prevented increases in plasma
      triglyceride contents in rats insulted with CCl4 or BSO+CCl4. The present study
      demonstrated that GO+DDB, when daily pretreated for six consecutive days, exerted
      synergistic protection of the liver from chemical-induced injury potentiated by
      the condition of GSH deficiency, and has additional advantages in lowering the
      plasma lipids.

PMID- 15950963
TI  - Regeneration of cryoresistance of in vitro rumen ciliate cultures.
AB  - The purpose of this study was to investigate factors affecting mechanical- and
      cryo-resistance of the rumen ciliates Entodinium caudatum (E.c.), Entodinium
      furca monolobum (E.f.m.), Entodinium simplex (E.s.), Diplodinium denticulatum
      (two clones, D.d.01 and D.d.02), Diploplastron affine (D.a.) and Epidinium
      ecaudatum forma caudatum (E.e.c.) after long-term in vitro cultivation. Following
      prolonged in vitro cultivation (more than six months), the ciliates were very
      sensitive to both centrifugation and 5% (v/v) dimethylsulphoxide, with motility
      decreased to: 39 and 23% for E.c., 66 and 32% for E.f.m., 46 and 27% for D.d. 01,
      64 and 41% for D.a., and 44 and 28% for E.e.c., respectively. Thus,
      cryopreservation was unsuccessful. The effect of supplementing the ciliate growth
      medium with rumen fluid, glycine-betaine, proline, myo-inositol, linoleic acid,
      Sel-Plex or insulin, together with the effect of the source of rumen fluid on
      ciliate resistance to centrifugation, dimethylsulphoxide and freezing was also
      tested. The omission of rumen fluid from the growth medium resulted in the loss
      of cryoresistance after one-month cultivation. Supplementing the growth
      environment with a combination of glycine-betaine, proline, linoleic acid, Sel
      Plex, insulin plus improved quality rumen fluid significantly enhanced survival
      of the ciliates after the freezing-thawing procedure (from 1 to 33% survival in
      un-supplemented vs. supplemented for E.c., P<0.01; 4-40% E.f.m., P<0.01; 0-17%
      D.d., P<0.05; 5-7% D.a. and 4-36% E.e.c., P<0.01).

PMID- 15950964
TI  - YC-1-inhibited proliferation of rat mesangial cells through suppression of cyclin
      D1-independent of cGMP pathway and partially reversed by p38 MAPK inhibitor.
AB  - This study was designed to investigate the effect of 1-benzyl-3-(5'-hydroxymethyl
      2'-furyl) indazole (YC-1), a guanylate cyclase activator, upon the proliferation
      of rat mesangial cells and its underlying mechanism. YC-1 inhibited cell
      proliferation and DNA synthesis in a dose- and time-dependent manner. Flow
      cytometry cell-cycle studies revealed that YC-1 prevented the entry of cells from
      G1 into S phase. The expression of cyclin D1 and the kinase activity of cyclin
      D1/cyclin-dependent kinase (CDK)4 were lower within YC-1-treated cells, revealed
      by Western blotting, Northern blotting and kinase assays. YC-1 did not increase
      the intracellular cGMP concentration in mesangial cells. Inhibitors of soluble
      guanylate cyclase, protein kinase G, or protein kinase A also did not reverse the
      inhibitory effect elicited by YC-1, while co-treatment with p38 mitogen-activated
      protein kinase (MAPK) inhibitor could partially reverse the suppressive effect.
      YC-1 inhibited proliferation of mesangial cells and induced cell-cycle arrest by
      the reduction of cyclin D1 synthesis and cyclin D1/CDK4 kinase activity. This
      effect acts partially through p38 MAPK signal transduction activation and is
      independent of cGMP-signaling pathways.

PMID- 15950965
TI  - Lack of specific immunological disease pattern in vulvar lichen sclerosus.
AB  - The literature suggests that autoantibody formations and disturbances in cellular
      or humoral immunities are relevant immunological events in lichen sclerosus (LS).
      We examined 39 patients (age range: 7-81 years) enrolled in this experimental
      immunopathology study and treated for vulvar LS. In the serum, we used 88
      clinical immunology parameters to evaluate the immunological patterns, i.e.,
      autoimmune phenomena, humoral immunity, cellular immunity, and inflammation. The
      analyses permitted direct comparison of the measured distributions of alternative
      data. We found that all pathological findings of single immunological events
      followed a random distribution without any positive or negative trend or a
      distribution with a negative trend. There was a lack of correlation between the
      majority of cases and the presence of pathological findings (confidence intervals
      0.950 and 0.999). Combinations of two or more of the four patterns did not
      improve the outcomes (confidence intervals 0.950 and 0.999). However,
      abnormalities in systemic immune parameters implying system impairments might
      have occurred long before the patients with such a chronic disease presented to
      the clinic. This may be especially true of such diseases as vulvar LS, where
      local skin scarring might represent a local tissue response secondary to an
      initial insult by immune or other processes.

PMID- 15950966
TI  - Role of Rho, Rac, and Rho-kinase in phosphorylation of myosin light chain,
      development of polarity, and spontaneous migration of Walker 256 carcinosarcoma
      cells.
AB  - As previously shown, constitutive activation of the small GTPase Rho and its
      downstream target Rho-kinase is crucial for spontaneous migration of Walker
      carcinosarcoma cells. We now show that after treatment of cells with either the
      Rho inhibitor C3 exoenzyme or the Rho-kinase inhibitor Y-27632, constitutive
      myosin light chain (MLC) phosphorylation is significantly decreased, correlating
      with inhibition of cell polarization and migration. Transfection with a dominant
      negative Rho-kinase mutant similarly inhibits cell polarization and MLC
      phosphorylation. Transfection with a dominant-active Rho-kinase mutant leads to
      significantly increased MLC phosphorylation, membrane blebbing, and inhibition of
      cell polarization. This Rho-kinase-induced membrane blebbing can be inhibited by
      Y-27632, ML-7, and blebbistatin. Unexpectedly, overactivation of RhoA has similar
      effects as its inhibition. Introduction of a bacterially expressed constitutively
      activated mutant protein (but not of wild-type RhoA) into the cells or
      transfection of cells with a constitutively active RhoA mutant both inhibit
      polarization and decrease MLC phosphorylation. Transfection of cells with
      constitutively active or dominant-negative Rac both abrogate polarity, and the
      latter inhibits MLC phosphorylation. Our findings suggest an important role of
      Rac, Rho/Rho-kinase, and MLCK in controlling myosin activity in Walker
      carcinosarcoma cells and show that an appropriate level of RhoA, Rac, and Rho
      kinase activity is required to regulate cell polarity and migration.

PMID- 15950968
TI  - Cross-talk between the calcium-sensing receptor and the epidermal growth factor
      receptor in Rat-1 fibroblasts.
AB  - The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that is
      activated by extracellular calcium (Cao2+). Rat-1 fibroblasts have been shown to
      proliferate and increase ERK activity in response to elevation of [Ca2+]o, and
      these responses are dependent on functional CaR expression. In this report, we
      examined the role of cross-talk between the CaR and the epidermal growth factor
      receptor (EGFR) in mediating these responses in Rat-1 cells. This report shows
      that AG1478, a specific inhibitor of the EGFR kinase, significantly inhibits the
      increase in proliferation induced by elevated Cao2+. Furthermore, we show that
      AG1478 acts downstream or separately from G protein subunit activation of
      phospholipase C. AG1478 significantly inhibits Cao2+-stimulated ERK
      phosphorylation and in vitro kinase activity. A similar inhibition of ERK
      phosphorylation was observed in response to the inhibitor AG494. In addition,
      treatment with inhibitors of metalloproteases involved in shedding of membrane
      anchored EGF family ligands substantially inhibited the increase in ERK
      activation in response to elevated Cao2+. This is consistent with the known
      expression of TGFalpha by Rat-1 cells. These results indicate that EGFR
      transactivation is an important component of the CaR-mediated response to
      increased Cao2+ in Rat-1 fibroblasts and most likely involves CaR-mediated
      induction of regulated proteolysis and ligand shedding.

PMID- 15950967
TI  - Phylogenetic conservation of the regulatory and functional properties of the Vav
      oncoprotein family.
AB  - Vav proteins are phosphorylation-dependent GDP/GTP exchange factors for Rho/Rac
      GTPases. Despite intense characterization of mammalian Vav proteins both
      biochemically and genetically, there is little information regarding the
      conservation of their biological properties in lower organisms. To approach this
      issue, we have performed a characterization of the regulatory, catalytic, and
      functional properties of the single Vav family member of Drosophila melanogaster.
      These analyses have shown that the intramolecular mechanisms controlling the
      enzyme activity of mammalian Vav proteins are already present in Drosophila,
      suggesting that such properties have been set up before the divergence between
      protostomes and deuterostomes during evolution. We also show that Drosophila and
      mammalian Vav proteins have similar catalytic specificities. As a consequence,
      Drosophila Vav can trigger oncogenic transformation, morphological change, and
      enhanced cell motility in mammalian cells. Gain-of-function studies using
      transgenic flies support the implication of this protein in cytoskeletal
      dependent processes such as embryonic dorsal closure, myoblast fusion, tracheal
      development, and the migration/guidance of different cell types. These results
      highlight the important roles of Vav proteins in the signal transduction pathways
      regulating cytoskeletal dynamics. Moreover, they indicate that the foundations
      for the regulatory and enzymatic activities of this protein family have been set
      up very early during evolution.

PMID- 15950969
TI  - Immunolocalization of retinoic acid biosynthesis systems in selected sites in
      rat.
AB  - Vitamin A deficiency leads to focal metaplasia of numerous epithelial tissues
      with altered differentiation from columnar (in general) to stratified squamous
      cells. This process can be reversed with vitamin A repletion. Previously, we
      described a system of retinoic acid (RA) synthesis in the cycling rat uterus
      consisting of cellular retinol binding protein (Crbp), epithelial retinol
      dehydrogenase (eRoldh), retinal dehydrogenase 2 (Aldh1a2), and cellular retinoic
      acid binding protein type II (Crabp2). Western blot analysis, RT-PCR, and
      immunohistochemistry were performed to test whether this retinoic acid synthesis
      system was also present in other vitamin A sensitive tissues. We found that
      combinations of Crbp, eRoldh, Aldh1a2 or Aldh1a3, and Crabp2 were present in all
      vitamin A sensitive tissues examined. In the ureter, while eRoldh was present,
      another short chain alcohol dehydrogenase reductase (possibly Roldh 1, 2, or 3)
      was in higher concentration in the transitional epithelia. In several tissues,
      Crbp, Aldh1a2, and/or Aldh1a3 localized to mesenchyme and/or epithelial cells,
      while eRoldh and Crabp2 were expressed only in epithelial cells. This suggests
      that mesenchymal-epithelial interactions may be as important in the adult as they
      are during development and that local synthesis of RA is important in maintenance
      of these tissues.

PMID- 15950970
TI  - Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation.
AB  - Regeneration of axons in the peripheral nervous system is enhanced by the removal
      of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans.
      However, some axons regenerate poorly despite such treatment, suggesting the
      existence of additional inhibitors. We compared the effects of enzymatic removal
      of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan
      species, heparan sulfate and keratan sulfate proteoglycans, on the regeneration
      of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and
      repaired using short segments of CF nerves harvested from wild-type littermates
      and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal
      regeneration was assayed by measuring the lengths of profiles of YFP+ axons in
      optical sections of the grafted nerves 1 week later. Except for grafts treated
      with keratanase, more and longer axon profiles were encountered in enzyme-treated
      grafts than in control grafts. Heparinase III treatments induced the greatest
      number of axons to enter into the graft. The proportions of axon profiles longer
      than 1000 microm were greater in grafts treated with chondroitinase ABC or
      heparinase I, but not with either keratanase or heparinase III. More regenerative
      sprouts were observed after treatment with heparinase I than any other enzymes.
      Treatment with a mixture of all four enzymes resulted in an enhancement of axon
      regeneration which was greater than that observed after treatment with any of the
      enzymes individually. The effects of chondroitinase ABC and heparinase III were
      correlated with specific GAG degradation. We believe that enzymatic removal of
      GAGs is especially effective in promoting the ability of regenerating axons to
      select their pathway in the distal stump (or nerve graft) and, in the case of
      chondroitinase ABC or heparinase I, it may also promote growth within that
      pathway.

PMID- 15950971
TI  - The therapeutic window of hypothermic neuroprotection in experimental ischemic
      neuropathy: protection in ischemic phase and potential deterioration in later
      reperfusion phase.
AB  - Hypothermia will neuroprotect peripheral nerve from ischemia-reperfusion (IR)
      injury, but the therapeutic window of hypothermic neuroprotection has not been
      defined. Unilateral IR injury was produced by the ligation and release of nooses
      tied around supplying arteries to the right sciatic-tibial nerve of the rat.
      Using this model, 114 rats were divided into 12 groups according to the delay (0,
      1, 3, and 4 h) and the depth of hypothermia (28, 32, and 35 degrees C). All rats
      were subjected to 3 h ischemia and 7 days reperfusion followed by behavioral,
      electrophysiological, and pathological evaluations. We demonstrated significant
      hypothermic neuroprotection with both deep (28 degrees C) and mild (32 degrees C)
      hypothermia initiated during ischemia (0 and 1 h delay), but not hypothermia
      initiated during reperfusion (3 and 4 h delay) in both behavioral and
      electrophysiological evaluations. In addition, the pathologically significant
      differences were observed between deep hypothermia (28 degrees C) and
      normothermia (35 degrees C) initiated during ischemia. We conclude that the
      therapeutic window of hypothermic neuroprotection is optimal during the
      intraischemic period and that mild and deep hypothermia provide neuroprotection.
      Prolonged delay of hypothermic treatment results in worsening of IR injury.

PMID- 15950972
TI  - Characterization of ABC transporter ABCB1 expressed in human neural
      stem/progenitor cells.
AB  - We investigated the localization and functional expression of the ABC transporter
      ABCB1 in human fetal neural stem/progenitor cells (hNSPCs). RT-PCR analysis
      revealed ABCB1 gene expression in hNSPCs. We found a single band in immunoblotted
      hNSPCs lysates probed with ABCB1 antibody, and detected ABCB1 at the hNSPCs cell
      membrane by immunocytochemistry and subcellular fractionation. ABCB1 inhibitors
      and substrate, and ATP-depleting agents enhanced hNSPCs' rhodamine 123
      accumulation, and hNSPCs microsomes had vanadate-sensitive ATPase activity. ABCB1
      and nestin expression decreased during hNSPCs differentiation, while the
      astroglial marker GFAP increased. ABCB1 may maintain hNSPCs in an
      undifferentiated state and could be a neural stem/progenitor marker.

PMID- 15950973
TI  - Synthesis, physicochemical and anticonvulsant properties of N-benzyl and N
      aminophenyl derivatives of 2-azaspiro[4.4]nonane and [4.5]decane-1,3-dione. Part
      I.
AB  - To continue our systematic SAR studies, two series of N-benzyl- (X=CH2) and N
      aminophenyl- (X=NH) derivatives of 2-azaspiro[4.4]nonane (1a-1j) and 2
      azaspiro[4.5]decane-1,3-dione (2a-2j) were synthesized, and evaluated in maximum
      electroshock seizure (MES), subcutaneous pentylenetetrazole (sc.MET) and rotorod
      (TOX) tests for their anticonvulsant activity. Among those derivatives, the most
      potent N-aminophenyl-2-azaspiro[4.4]nonane-1,3-dione 1j had ED50=76.27 mg kg-1. X
      ray structures for two pairs of derivatives with a different linker were solved.
      Then 3-D data for the active 1j versus less active 2j, both having an imine
      linker (X=NH), and the respective parent of compounds with a methylene linker
      (X=CH2) (1a and 2a) were discussed.

PMID- 15950974
TI  - Indoleamines and 5-methoxyindoles in trout pineal organ in vivo: daily changes
      and influence of photoperiod.
AB  - This study describes the diel rhythms in several indoleamines, melatonin, and
      related 5-methoxyindoles in the pineal organ of rainbow trout in vivo. In
      addition, the effect of different photoperiod conditions was evaluated. Melatonin
      levels displayed clear daily rhythms in the pineal organ of rainbow trout kept
      experimentally under long (LD 16:08), neutral (LD 12:12), and short (LD 08:16)
      photoperiods. Duration of melatonin signal was dependent on the night length of
      prevailing photoperiod, while peak amplitude was higher when lengthening the
      photoperiod. Significant daily rhythms in 5-HT content, the precursor of
      melatonin synthesis, were found in neutral and short photoperiod with increases
      of the amine content just after the light-dark interphase and decreases in the
      middle of the night, which were more important under short photoperiod. In
      contrast, no significant 24-h cyclic variation was found in pineal 5-HT content
      under long photoperiod. Daily profiles in the content of the main 5-HT oxidative
      metabolite, the 5-hydroxyindoleacetic acid (5-HIAA), outlined those of the amine
      precursor. The chronograms of both aminergic compounds contrast with those of 5
      hydroxytryptophan content, which displayed a net tendency to increase at night.
      This study also provides evidence for the existence of daily cyclic changes in
      the content of 5-methoxytryptamine (5-MT), 5-methoxyindoleacetic acid (5-MIAA),
      and 5-methoxytryptophol (5-MTOL) in trout pineal organ, which were also dependent
      on photoperiod. The 24-h profiles in 5-MT content correlated well with those of 5
      HT, showing a peak at the first hour of darkness in all photoperiodic conditions,
      and a decay at midnight only in both neutral and long photoperiods. Similarly,
      the content of 5-MTOL also displayed high values during the day-night transition
      in trout kept under neutral and long photoperiods, followed by a slow decay all
      along the night. Finally, levels of 5-MIAA increased in all photoperiods when
      lights were turned off, being this nocturnal increase maximal in fish kept under
      LD 16:08. These results suggest that light-dark cycle modulates daily rhythms in
      pineal indoles and non-melatonin 5-methoxyindoles by acting mainly through the
      melatonin synthesis activity, which limits the availability of 5-HT for the
      oxidative and direct methylation pathways. In addition, it seems that a
      nocturnally increased synthesis of 5-HT might be a requirement for the optimal
      formation of melatonin and other 5-methoxyindoles in the pineal organ when trout
      remain under short photoperiods.

PMID- 15950975
TI  - "Neuroethoendocrinology": integration of field and laboratory studies in insect
      neuroendocrinology.
AB  - Progress in the field of insect neuroendocrinology has been rapid despite the
      relatively small number of investigators working on insect systems. This
      progress, in part, reflects the ease of studying insect behavior in the
      laboratory, and a historical perspective reveals that insect neuroendocrinology
      has been dominated since its inception by laboratory studies. Recent advances in
      methodology and a renewed interest in the concept of behavioral state in insects
      suggest that it might be useful for insect neuroendocrinologists to spend a
      little more time in the field.

PMID- 15950976
TI  - In defense of nursing and the generic nurse.

PMID- 15950977
TI  - Single-channel properties of N- and L-subtypes of acetylcholine receptor in
      Ascaris suum.
AB  - We are interested in the properties of the target site of cholinergic anti
      nematodal drugs for therapeutic reasons. The target receptors are ligand-gated
      ion channels that have different subtypes, and each subtype may have a different
      pharmacology. In a contraction assay using the parasitic nematode Ascaris suum,
      our laboratory has identified several subtypes, including an N-subtype,
      preferentially activated by nicotine, and an L-subtype, preferentially activated
      by levamisole. Here we use patch-clamp recordings to test the hypothesis that the
      single-channel selectivities of nicotine and levamisole are different. Unitary
      currents evoked by nicotine in this preparation were characterised for the first
      time. In some patches, both nicotine and levamisole activated small- and large
      conductance channels. In other patches, the agonists activated just one channel
      amplitude. Discriminant analysis allowed classification of the one-conductance
      patch channels into the small or large categories, based on sets defined by the
      two-conductance patch data. The small channels had a conductance of 26.1+/-1.5
      pS, n=18 (mean+/-SEM); the large conductance channels had a conductance of 38.8+/
      1.2 pS, n=23 (mean+/-SEM). Analysis of amplitude histograms of the two
      conductance patches showed that nicotine preferentially activated the small
      conductance channels and levamisole preferentially activated the large
      conductance channels. Our observations suggest that the N-subtype receptor
      channel has a conductance of 26 pS channel and the L-subtype receptor channel has
      a conductance of 39 pS.

PMID- 15950978
TI  - Leptin receptor and functional effects of leptin in human endothelial progenitor
      cells.
AB  - Circulating endothelial progenitor cells (EPCs) may be involved in the
      maintenance of vascular homeostasis and their impairment may be conducive to
      vascular disease. We studied the role of an adipocyte-derived hormone, leptin, in
      the regulation of human EPC function. EPCs were grown from human circulating
      mononuclear cells. The presence of the leptin receptor and the functional effects
      of leptin in EPCs were investigated. EPCs stained positive for endothelial cell
      markers (Flk-1 and Tie-2 receptors) and the hematopoietic CD34 marker. The
      presence of the long form of the leptin receptor in EPCs was confirmed by Western
      blotting and with immunofluorescence. Leptin, at a physiological concentration of
      10 ng/ml, significantly increased tube formation from 2.1+/-2.2 to 12.4+/-4.9
      tubes/25 mm2. At a higher concentration of 100 ng/ml of leptin, tube formation
      was reduced compared to the lower concentration. This higher concentration of
      leptin also inhibited EPC migration, decreasing it from 0.45+/-0.14 to 0.28+/
      0.12 mm/48 h. Leptin did not have any effect on EPC proliferation. In summary,
      the leptin receptor is present in human EPCs and leptin may affect EPC function,
      both in physiological and in hyperleptinemic conditions. These findings are
      relevant to leptin-mediated regulation of vasculogenesis in humans, and the
      association between hyperleptinemia and obesity with cardiovascular disease.

PMID- 15950979
TI  - Finite element analysis of a total ankle replacement during the stance phase of
      gait.
AB  - Total ankle replacement (TAR) designs have still several important issues to be
      addressed before the treatment becomes fully acceptable clinically. Very little
      is known about the performance, in terms of the contact pressures and kinematics
      of TAR when subjected to daily activities such as level gait. For this purpose,
      an explicit finite element model of a novel 3-component TAR was developed, which
      incorporated a previously validated mechanical model of the ankle ligament
      apparatus. The intermediate mobile polyethylene meniscal bearing was modelled as
      an elastic-plastic continuum while the articulating surfaces of the tibial and
      talar metal components as rigid bodies. Overall kinematics, contact pressures and
      ligament forces were analysed during passive, i.e. virtually unloaded, and
      active, i.e. stance phase of gait, conditions. Simulation of passive motion
      predicted similar kinematics as reported previously in an analytical four-bar
      linkage model. The meniscal bearing was observed to move 5.6 mm posteriorly
      during the simulated stance and the corresponding antero-posterior displacement
      of the talar component was 8.3 mm. The predicted pattern and the amount (10.6
      degrees ) of internal-external rotation of the ankle complex were found to be in
      good agreement with corresponding in vivo measurements on normal ankles. A peak
      contact pressure of 16.8 MPa was observed, with majority of contact pressures
      below 10 MPa. For most ligaments, reaction forces remain within corresponding
      physiological ranges. A first realistic representation of the biomechanical
      behaviour of the human ankle when replaced by prosthetic joints is provided. The
      applied methodology can potentially be applied to other TAR designs.

PMID- 15950980
TI  - The effect of swimmer's hand/forearm acceleration on propulsive forces generation
      using computational fluid dynamics.
AB  - Propulsive forces generated by swimmers hand/forearm, have been studied through
      experimental tests. However, there are serious doubts as to whether forces
      quantified in this way are accurate enough to be meaningful. In order to solve
      some experimental problems, some numerical techniques have been proposed using
      Computational Fluid Dynamics (CFD). The main purpose of the present work was
      threefold. First, disseminate the use of CFD as a new tool in swimming research.
      Second, apply the CFD method in the calculation of drag and lift coefficients
      resulting from the numerical resolution equations of the flow around the swimmers
      hand/forearm using the steady flow conditions. Third, evaluate the effect of
      hand/forearm acceleration on drag and lift coefficients. For these purposes
      three, two-dimensional (2D), models of a right male hand/forearm were studied. A
      frontal model (theta = 90 degrees, Phi = 90 degrees) and two lateral models, one
      with the thumb as leading edge (theta = 0 degrees, = 90 degrees), and the other
      with the small finger as the leading edge (theta = 0 degrees, Phi = 180 degrees).
      The governing system of equations considered was the incompressible Reynolds
      averaged Navier-Stokes equations with the standard k-epsilon model. The main
      results reported that, under the steady-state flow condition, the drag
      coefficient was the one that contributes more for propulsion, and was almost
      constant for the whole range of velocities, with a maximum value of 1.16 (Cd =
      1.16). This is valid when the orientation of the hand/forearm is plane and the
      model is perpendicular to the direction of the flow. Under the hand /forearm
      acceleration condition, the measured values for propulsive forces calculation
      were approximately 22.5% (54.440 N) higher than the forces produced under the
      steady flow condition (44.428 N). By the results, pointed out, we can conclude
      that: (i) CFD can be considered an interesting new approach for hydrodynamic
      forces calculation on swimming, (ii) the acceleration of hand/forearm provides
      more propulsion to swimmers, confirming that some unsteady mechanism must be
      present in swimming propulsion.

PMID- 15950981
TI  - Control of n-alkanes crystallization by ethylene-vinyl acetate copolymers.
AB  - The crystallization of paraffins from their solution at low temperature was
      investigated in the presence of ethylene-vinyl acetate (EVA) copolymers that
      allow the control of the size of the crystals. Depending on the type of solvent
      and distribution of the paraffin lengths, the mechanisms of crystal formation and
      growth are different. Precipitation of the EVA prior to the paraffins leads to
      the nucleation of a large number of crystals, whereas the adsorption of EVA on
      the surface of the growing crystals slows down the crystal growth. EVA can act
      either as a nucleating agent or as a growth inhibitor. These two mechanisms were
      identified from the analysis of the temperature of crystallization (cloud point),
      the chemical composition of the crystals, and the observations of the crystal
      habit. The EVA was able to co-crystallize with the paraffins in crystals of an
      orthorhombic structure and the melting enthalpies of the crystalline paraffin did
      not depend significantly on their neighborhood. The energies of interaction
      between the different paraffinlike components are close to each other, so that
      minor changes of the experimental conditions may lead to dramatic effects. This
      is the basic rationale for the large behavioral diversity observed in these
      systems.

PMID- 15950982
TI  - Rapid preparation and characterization of uniform, large, spherical Ag particles
      through a simple wet-chemical route.
AB  - In this article we report the rapid preparation of uniform, large, spherical Ag
      particles through a simple wet-chemical route. The formation of Ag particles with
      about 750 nm in diameter occurs in a single process, carried out by direct mix of
      AgNO3 aqueous solution and ortho-phenylenediamine N-methyl-2-pyrrolidone solution
      at room temperature, producing a relatively low-polydispersity product. It is
      also found that raising the temperature results in larger particles. Scanning
      electron microscopy, transmission electron microscopy, X-ray diffraction, and X
      ray photoelectron spectra have been used to characterize the resulting product.

PMID- 15950983
TI  - Auditory-visual speech integration by adults with and without language-learning
      disabilities.
AB  - Auditory and auditory-visual (AV) speech perception skills were examined in
      adults with and without language-learning disabilities (LLD). The AV stimuli
      consisted of congruent consonant-vowel syllables (auditory and visual syllables
      matched in terms of syllable being produced) and incongruent McGurk syllables
      (auditory syllable differed from visual syllable). Although the identification of
      the auditory and congruent AV syllables was comparable for the two groups, the
      reaction times to identify all syllables were longer in the LLD compared to the
      control group. This finding is consistent with previous research demonstrating
      slower processing in learning disabled individuals. Adults with LLD also provided
      significantly fewer integration-type or McGurk responses compared with their
      normal peers when presented with speech tokens representing a mismatch between
      the auditory and visual signal. These results suggest the poor integration for
      auditory-visual speech previously documented in children with poor language
      skills also occurs in adults with LLD. LEARNING OUTCOMES: The reader will be able
      to (1) describe the McGurk effect; (2) describe group differences (language
      learning disabled and control adults) in auditory and auditory-visual speech
      perception of consonant-vowel syllables.

PMID- 15950984
TI  - A quantitative and qualitative assessment of verbal short-term memory and
      phonological processing in 8-year-olds with a history of repetitive otitis media.
AB  - Language outcome in children experiencing fluctuant hearing loss due to otitis
      media (OME) remains highly equivocal. In the current study, we assessed
      performance on highly sensitive verbal short-term memory (STM), new word learning
      and phonological processing tasks in 8-year-old children who had suffered from
      recurrent OME before the age of 3. Relative to a control group with no history of
      OME, we observed strictly normal performance for different STM and new word
      learning tasks. Performance on these tasks was also normally influenced by
      phonotactic, lexical and semantic variables. However, at the level of
      phonological processing, a small but significant decrease of performance was
      found in a speeded nonword identification task and a rhyme judgment task. The
      results of this study suggest that outcome of OME is characterized by subtle
      impairments at the level of perceptual-phonological analysis, but there is no
      significant impact on verbal STM and new word learning abilities. LEARNING
      OUTCOMES: As a result of this activity, the participant will be able to (1)
      explain the outcome of recurrent OME before age 3 on later language and verbal
      STM development, (2) be aware of the complex relationships that link language
      development and verbal STM, (3) explain how fluctuant hearing loss during infancy
      and early childhood could affect verbal STM development and learning capacity for
      new phonological information, (4) describe different verbal STM measures that
      distinguish retention capacities for phonological and lexico-semantic
      information, and (5) explain the influence of phonotactic frequency on nonword
      processing in language and verbal STM tasks.

PMID- 15950985
TI  - Prevention of cardiac remodeling after myocardial infarction in transgenic rats
      deficient in brain angiotensinogen.
AB  - The brain renin-angiotensin-aldosterone system (RAAS) plays a major role in
      cardiac remodeling after myocardial infarction (MI). To assess the contribution
      of the brain RAAS in the activation of the cardiac RAAS post-MI, transgenic (TG)
      rats deficient in brain angiotensinogen and Wistar rats with
      intracerebroventricular (ICV) infusion of spironolactone were studied. An MI was
      induced by acute coronary artery ligation. TG and control Sprague-Dawley (SD)
      rats were followed for 8 weeks and Wistar rats for 6 weeks. Infarct sizes, % of
      left ventricle (LV) area, were in the 30-33% range. In SD rats at 8 weeks post
      MI, internal circumference, interstitial and perivascular fibrosis, cardiomyocyte
      diameter in the LV and right ventricle (RV), laminin and fibronectin in the LV,
      and lung weights were increased. Aldosterone was increased markedly in both the
      LV and RV at 8 weeks post-MI. In TG rats, the MI-induced increases of RV internal
      circumference and weight were prevented and increases of lung weight and LV
      internal circumference were significantly inhibited. In TG rats, the post-MI
      increases of interstitial fibrosis and cardiomyocyte diameter were prevented in
      septum and RV and significantly inhibited in the peri-infarct zone of the LV. The
      increases in perivascular fibrosis, laminin and fibronectin were prevented in the
      LV. In TG rats, cardiac aldosterone did not increase. In Wistar rats at 6 weeks
      post-MI, aldosterone was markedly increased in the LV, but not in the RV. This
      increase was prevented by ICV infusion of spironolactone. These findings support
      the pivotal role of locally produced angiotensin II in the brain in cardiac
      remodeling post-MI. The brain RAAS appears to activate a cascade of events, among
      others an increase in cardiac aldosterone, which play a major role in cardiac
      remodeling post-MI.

PMID- 15950986
TI  - SRF-dependent gene expression in isolated cardiomyocytes: regulation of genes
      involved in cardiac hypertrophy.
AB  - Serum response factor (SRF) is a transcription factor required for the regulation
      of genes important for cardiac structure and function. Notably, the "fetal gene
      expression profile" that is characteristic of cardiac hypertrophy consists of
      genes known to be regulated by SRF. Transgenic animal studies suggest that
      cardiac-specific overexpression of SRF induces this pattern of hypertrophic genes
      and subsequently causes the progression of pathologic adaptations. Furthermore,
      studies examining cardiac tissues from patients with severe heart failure
      indicate significant alterations in SRF expression that correspond with
      alterations in expression of SRF-dependent genes. Based on these observations, it
      has been postulated that SRF may be critical for stimulating pathologic gene
      expression at the onset of hypertrophic adaptation. To address the role of SRF in
      cardiac hypertrophy we investigated whether SRF is necessary and sufficient for
      the expression of genes associated with the hypertrophic response. We used
      isolated cardiomyocytes from both neonatal rats, and transgenic mice containing
      floxed SRF alleles, to examine cardiac gene expression in response to
      overexpression and absence of SRF. Using this approach, we demonstrate that SRF
      is required for the induction of atrial naturetic factor (ANF), c-fos, NCX1, BNP,
      alpha-actins, alpha-myosin heavy chain, and beta-myosin heavy chain genes.
      However, overexpression of exogenous SRF in isolated cardiomyocytes is only
      sufficient to induce NCX1 and alpha-myosin heavy chain. These results indicate
      that SRF is critical for the regulation and induction of genes associated with
      the progression of pathologic cardiac hypertrophy, however, the pattern of genes
      induced by overexpression of SRF in isolated cardiomyocytes is different from
      those genes expressed in hypertrophic transgenic hearts. This suggests that SRF
      dependent gene expression is modulated in a complex manner by in vivo physiologic
      systems prior to and during heart failure as the organism adapts to cardiac
      stress.

PMID- 15950987
TI  - Differential functional effects of two 5-HT4 receptor isoforms in adult
      cardiomyocytes.
AB  - Serotonin 5-HT4 receptors are present in human atrial myocytes and have been
      proposed to contribute to the generation of atrial fibrillation. However, 5-HT4
      receptors have so far been only found in human and pig atria and are absent from
      the heart of small laboratory animals, such as rat, guinea pig, rabbit and frog,
      which limits the experimental settings for studying their functional properties.
      In this study, we developed an adenovirus expression system to examine the
      properties of two human 5-HT4 receptor splice variants, h5-HT4(b) and h5-HT4(d),
      expressed in adult cardiomyocytes devoid of native 5-HT4 receptors. When
      expressed in the HL-1 murine cell line of atrial origin, both receptors caused
      specific binding of the 5-HT4 selective antagonist GR113808 and activated
      adenylyl cyclase in the presence of serotonin (5-HT, 1 microM). When expressed in
      freshly isolated adult rat ventricular cardiomyocytes, a stimulation of the L
      type Ca2+ current (ICa,L) by 5-HT (100 nM) was revealed. Both effects were
      blocked by GR113808. In HL-1 cells, the h5-HT4(d) receptor was found to be more
      efficiently coupled to adenylyl cyclase than the h5-HT4(b). Pertussis toxin
      treatment (250 ng/ml for 5 h) potentiated the stimulatory effect of 5-HT on ICa,L
      in rat myocytes expressing the h5-HT4(b) but not the h5-HT4(d) receptor,
      indicating a likely coupling of the (b) isoform to both Gs and Gi/o proteins.
      Adenoviral expression of h5-HT4 receptor isoforms in adult cardiac myocytes
      provides a valuable means for the exploration of the receptor signaling cascades
      in normal and pathological situations.

PMID- 15950988
TI  - Modeling the Parkinson's tremor and its treatments.
AB  - In this paper, we discuss modeling issues of the Parkinson's tremor. Through the
      work we have employed physiological structure as well as functioning of the parts
      in brain that are involved in the disease. To obtain more practical similarity,
      random behaviors of the connection paths are also considered. Medication or
      treatment of the disease both by drug prescription and electrical signal
      stimulation are modeled based on the same model introduced for the disease
      itself. Two new medication strategies are proposed based on the model to reduce
      the side effects caused by the present drug prescription.

PMID- 15950989
TI  - Lipids as bioeffectors in the immune system.
AB  - Lipids, in addition to serving as fuel stores and structural components of cell
      membranes, act as effectors and second messengers in a variety of biological
      processes including those associated with the immune system. These lipid
      mediators and regulators differ in structural composition and exert a diverse
      array of effects on cellular functional activities including those linked to
      homeostasis, immune responsiveness, and inflammation. They function as
      intercellular mediators and at the intracellular level act as critical conduits
      of external stimuli in signal transduction cascades. Lipid derived messengers and
      their receptors also may interact with other signaling molecules. Exogenous
      compounds such as cannabinoids share functionally relevant receptor binding
      domains with those for endogenous lipid signaling ligands and have the potential
      to alter transductional cascades linked to immune functional activities.

PMID- 15950990
TI  - Guidelines for the use of AMBI (AZTI's Marine Biotic Index) in the assessment of
      the benthic ecological quality.

PMID- 15950991
TI  - New algorithms for Luria-Delbruck fluctuation analysis.
AB  - Fluctuation analysis is the most widely used approach in estimating microbial
      mutation rates. Development of methods for point and interval estimation of
      mutation rates has long been hampered by lack of closed form expressions for the
      probability mass function of the number of mutants in a parallel culture. This
      paper uses sequence convolution to derive exact algorithms for computing the
      score function and observed Fisher information, leading to efficient computation
      of maximum likelihood estimates and profile likelihood based confidence intervals
      for the expected number of mutations occurring in a test tube. These algorithms
      and their implementation in SALVADOR 2.0 facilitate routine use of modern
      statistical techniques in fluctuation analysis by biologists engaged in mutation
      research.

PMID- 15950992
TI  - Prostate cancer and the genomic revolution: Advances using microarray analyses.
AB  - The emerging technology of microarray analysis allows the establishment of
      molecular portraits of prostate cancer and the discovery of novel genes involved
      in the carcinogenesis process. Many novel genes have already been identified
      using this technique, and functional analyses of these genes are currently being
      tested. The combination of microarray analysis with other recently developed high
      throughput techniques, such as proteomics, tissue arrays, and gene promoter
      methylation, especially using tissue microdissection methods, will provide us
      with more comprehensive insights into how prostate cancer develops and responds
      to gene-targeted therapies. Animal models of prostate cancer are being
      characterized by high throughput techniques to better define the similarities and
      differences between those models and the human disease, and to determine whether
      particular models may be useful for specific targeted therapies in pre-clinical
      studies. Although profiling of mRNA expression provides important information of
      gene expression, the development of proteomic technologies will allow for an even
      more precise global insight into cellular signaling and structural alterations
      during prostate carcinogenesis. Not only will the "omic" revolution change basic
      science, but it will lead to a new era of molecular medicine.

PMID- 15950993
TI  - Anticonvulsant action of an antagonist of metabotropic glutamate receptors mGluR5
      MPEP in immature rats.
AB  - Antagonists of type I of metabotropic glutamate receptors exhibit anticonvulsant
      action in adult as well as immature rodents. To know the anticonvulsant profile
      of a specific mGluR5 antagonist MPEP in developing rats, two models of epileptic
      seizures were used. MPEP (10, 20 or 40 mg/kg i.p.) suppressed in a dose-dependent
      manner epileptic afterdischarges induced by electrical stimulation of
      sensorimotor cortical area in three age groups (12, 18 and 25 days old). The
      anticonvulsant action was more expressed in the youngest group than in older
      animals so that in 25-day-old rats an additional dose of 80 mg/kg was used. In
      contrast to this marked anticonvulsant action, MPEP at a dose of 40 mg/kg i.p. in
      18-day-old rat pups and at doses of 40 and 80 mg/kg in 25-day-old rat pups did
      not affect episodes of spike-and-wave rhythm elicited by low doses of
      pentetrazol. Our results delineate the profile of the anticonvulsant action of
      MPEP and confirm the higher efficacy of this antagonist at early developmental
      stages in comparison with prepubertal animals.

PMID- 15950994
TI  - Short-term steroid treatment increases delta GABAA receptor subunit expression in
      rat CA1 hippocampus: pharmacological and behavioral effects.
AB  - In this study, 48 h administration of 3alpha-OH-5beta-pregnan-20-one
      (3alpha,5beta-THP) or 17beta-estradiol (E2)+progesterone (P) to female rats
      increased expression of the delta subunit of the GABA(A) receptor (GABAR) in CA1
      hippocampus. Coexpression of alpha4 and delta subunits was suggested by an
      increased response of isolated pyramidal cells to the GABA agonist 4,5,6,7-
      tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), following 48 h steroid treatment,
      and nearly complete blockade by 300 microM lanthanum (La3+). Because
      alpha4betadelta GABAR are extrasynaptic, we also recorded pharmacologically
      isolated GABAergic holding current from CA1 hippocampal pyramidal cells in the
      slice. The La3+-sensitive THIP current, representative of current gated by
      alpha4betadelta GABAR, was measurable only following 48 h steroid treatment. In
      contrast, the bicuculline-sensitive current was not altered by steroid treatment,
      assessed with or without 200 nM gabazine to block synaptic current. However, 48 h
      steroid treatment resulted in a tonic current insensitive to the benzodiazepine
      agonists lorazepam (10 microM) and zolpidem (100 nM). These results suggest that
      48 h steroid treatment increases expression of alpha4betadelta GABAR which
      replace the ambient receptor population. Increased anxiolytic effects of THIP
      were also observed following 48 h steroid treatment. The findings from the
      present study may be relevant for alterations in mood and benzodiazepine
      sensitivity reported across the menstrual cycle.

PMID- 15950995
TI  - A comparative study of the sub-chronic toxic effects of three organic arsenical
      compounds on the urothelium in F344 rats; gender-based differences in response.
AB  - Epidemiological studies indicated that human arsenic exposure can induce urinary
      bladder cancer. Methylation of inorganic arsenic can generate more reactive and
      toxic organic arsenical species. In this regard, it was recently reported that
      the methylated arsenical metabolite, dimethylarsinic acid [DMA(V)], induced
      urinary bladder tumors in rats. However, other methylated metabolites, like
      monomethylarsonic acid [MMA(V)] and trimethylarsine oxide (TMAO) were not
      carcinogenic to the urinary bladder. In order to compare the early effects of
      DMA(V), MMA(V), and TMAO on the urinary bladder transitional cell epithelium at
      the scanning electron microscope (SEM) level, we investigated the sub-chronic (13
      weeks) toxicological effects of MMA(V) (187 ppm), DMA(V) (184 ppm), TMAO (182
      ppm) given in the drinking water to male and female F344 rats with a focus on the
      urinary bladder in this study. Obvious pathological changes, including ropy
      microridges, pitting, increased separation of epithelial cells, exfoliation, and
      necrosis, were found in the urinary bladders of both sexes, but particularly in
      females receiving carcinogenic doses of DMA(V). Urine arsenical metabolic
      differences were found between males and females, with levels of MMA(III), a
      potential genotoxic form, higher in females treated with DMA(V) than in males.
      Thus, this study provides clear evidence that DMA(V) is more toxic to the female
      urinary bladder, in accord with sensitivity to carcinogenesis. Important gender
      related metabolic differences including enhanced presentation of MMA(III) to the
      urothelial cells might possibly account for heightened sensitivity in females.
      However, the potential carcinogenic effects of MMA(III) need to be further
      elucidated.

PMID- 15950996
TI  - Mismatched hemagglutinin and neuraminidase specificities in recent human H3N2
      influenza viruses.
AB  - The hemagglutinin (HA) of influenza viruses initiates infection by binding to
      sialic acid on the cell surface via alpha2,6 (human) or alpha2,3 (avian) linkage.
      The influenza neuraminidase (NA) can cleave both alpha2,3- and alpha2,6-linked
      sialic acids, but all influenza NAs have a marked preference for the non-human
      alpha2,3 linkage. Recent H3N2 influenza viruses have lost the ability to
      agglutinate chicken red blood cells. To determine if changes in HA specificity or
      affinity correlate with NA specificity or activity, we examined red cell binding
      and elution of a series of H3N2 viruses. We found that the NA activity of many
      influenza viruses does not release binding by their HA. In some egg-adapted
      strains, lack of elution correlates with low levels of viral NA activity, and
      these elute rapidly when bacterial NA is added. However, a Fujian-like virus,
      A/Oklahoma/323/03, does not elute by its own NA or with Vibrio cholerae
      sialidase, and it binds to red cells pre-treated with V. cholerae sialidase. It
      elutes after addition of the broad specificity Micromonospora viridifaciens
      sialidase. Human glycophorin inhibits A/Oklahoma/323/03 hemagglutination 6-fold
      better than fetuin. We conclude that specific forms of sialic acid are used as
      receptor by recent human H3N2 influenza viruses, perhaps involving branched
      alpha2,6 sialic acid or alpha2,8 sialic acid structures on O-linked
      carbohydrates. The virus itself has no O-linked glycans, so even though the NA is
      not able to cleave receptors on cells, the viruses will not self-aggregate. It
      will be important to monitor efficacy of neuraminidase inhibitors in case there
      are NA-resistant receptors in the human respiratory tract that allow the viruses
      to be less dependent on NA activity.

PMID- 15950997
TI  - The role of simian virus 5 V protein on viral RNA synthesis.
AB  - The paramyxovirus simian virus 5 (SV5) has seven genes but encodes eight known
      viral proteins. The V/P gene is transcribed into two mRNA species: V mRNA from a
      faithful transcription of the gene and P mRNA from transcription with addition of
      two G residues at a specific site of the gene. V, a 222-amino acid (AA) residue
      protein, and P, a 392 AA residue protein, share an identical N-terminus domain of
      164 amino acid residues. P is essential for SV5 RNA replication and
      transcription. Whereas it is known that V plays important roles in virus
      pathogenesis, the role of V in SV5 replication and transcription is not clear. A
      mini-genome system, free of vaccinia virus gene expression system, consisting of
      plasmids expressing NP, P, and L, as well as a plasmid encoding a reporter gene,
      chloramphenicol acetyltransferase (CAT) flanked by SV5 trailer and leader
      sequences under control of a bacteriophage T7 RNA polymerase promoter, has been
      established to examine the role of V in SV5 RNA transcription and replication.
      Addition of V-expressing plasmid in the mini-genome system caused inhibition of
      the reporter gene expression, suggesting that V plays a role in regulating SV5
      gene expression. By examining the amount of encapsidated viral RNA genome using
      reverse transcription with primer annealing to viral anti-genome RNA and PCR, it
      was found that expression of V reduced the amount of viral RNA genome in the mini
      genome system, suggesting that V inhibits viral RNA replication. To examine
      whether the V protein inhibits viral RNA transcription as well, a mini-genome
      system with a defective anti-genome promoter (AGP) such that a reporter gene
      (luciferase, Luc) expression is only derived from transcription of newly produced
      mini-genome and not from de novo replicated viral genome due to the defect in
      replication element has been utilized. The V protein inhibited luciferase
      expression from the mini-genome with a defective AGP, suggesting V inhibits SV5
      transcription. Thus, SV5 V inhibits both SV5 RNA replication and transcription.

PMID- 15950998
TI  - Neutralization of a common cold virus by concatemers of the third ligand binding
      module of the VLDL-receptor strongly depends on the number of modules.
AB  - Concatemers of various numbers of the third ligand binding repeat of human very
      low density lipoprotein receptor arranged in tandem were fused to maltose-binding
      protein and expressed as soluble polypeptides. These artificial receptors
      protected HeLa cells against infection with human rhinovirus serotype 2 (HRV2) to
      a degree that strongly increased with the number of repeats present; maximal
      protection was seen for the pentameric concatemer (MBP-V33333). This V3 pentamer
      neutralized HRV2 more efficiently than a recombinant protein with the entire
      ligand binding domain of the native receptor encompassing all 8 non-identical
      repeats. A concatemer of seven V3 modules (MBP-V3333333) was also less
      neutralizing. Neutralization was correlated with the degree of inhibition of
      virus binding to the cell surface. The results were in agreement with kinetic
      measurements using Biacore instrumentation demonstrating an increase in avidity
      with the number of modules present. At low concentrations of the receptor
      fragments, a 1:1 Langmuir kinetics was observed which became of complex type in
      the higher concentration range. This is most likely a consequence of receptor
      molecules simultaneously binding via several modules. Since there is no viral
      aggregation, neutralization of viral infectivity results from blockage of the
      receptor binding sites and possibly from inhibition of viral uncoating by
      crosslinking the viral capsid subunits via multi-module binding. Finally, the low
      affinity of the single V3 module allowed demonstrating the possibility of mapping
      the binding epitope of the V3 receptor fragment by saturation transfer difference
      nuclear magnetic resonance methodology.

PMID- 15950999
TI  - Disruption of the putative splice acceptor site for SIV(mac239)Vif reveals tight
      control of SIV splicing and impaired replication in Vif non-permissive cells.
AB  - Vif is dispensable for simian immunodeficiency virus (SIV) replication in some
      cells, termed permissive (i.e., CEM-SS), but not in others, termed non-permissive
      (i.e., H9, CEMx174, and peripheral blood lymphocytes). Non-permissive cells
      express the RNA editing enzyme, APOBEC3G. To determine whether vif mRNA could be
      alternatively spliced, a mutation altering the putative vif splice acceptor site
      (SA1) was introduced into SIV(mac239) (SIV(Deltavif-SA)). Despite three consensus
      splice acceptor sites nearby SA1, SIV(Deltavif-SA) did not efficiently generate
      alternatively spliced vif mRNA. SIV(Deltavif-SA) was growth attenuated in CEMx174
      and H9 cells but not in CEM-SS cells. Following SIV(Deltavif-SA), but not
      SIV(mac239), infection in either H9 or CEMx174 cells viral cDNA contained
      numerous G to A mutations; no such differences were observed in CEM-SS cells.
      This pattern is consistent with mutations generated by APOBEC3G in the absence of
      Vif. Therefore, efficient splicing of SIV vif mRNA is tightly controlled and
      requires the SA1 site.

PMID- 15951000
TI  - Sequence analysis of the complete genome of Trichoplusia ni single
      nucleopolyhedrovirus and the identification of a baculoviral photolyase gene.
AB  - The genome of the Trichoplusia ni single nucleopolyhedrovirus (TnSNPV), a group
      II NPV which infects the cabbage looper (T. ni), has been completely sequenced
      and analyzed. The TnSNPV DNA genome consists of 134,394 bp and has an overall G +
      C content of 39%. Gene analysis predicted 144 open reading frames (ORFs) of 150
      nucleotides or greater that showed minimal overlap. Comparisons with previously
      sequenced baculoviruses indicate that 119 TnSNPV ORFs were homologues of
      previously reported viral gene sequences. Ninety-four TnSNPV ORFs returned an
      Autographa californica multiple NPV (AcMNPV) homologue while 25 ORFs returned
      poor or no sequence matches with the current databases. A putative photolyase
      gene was also identified that had highest amino acid identity to the photolyase
      genes of Chrysodeixis chalcites NPV (ChchNPV) (47%) and Danio rerio (zebrafish)
      (40%). In addition unlike all other baculoviruses no obvious homologous repeat
      (hr) sequences were identified. Comparison of the TnSNPV and AcMNPV genomes
      provides a unique opportunity to examine two baculoviruses that are highly
      virulent for a common insect host (T. ni) yet belong to diverse baculovirus
      taxonomic groups and possess distinct biological features. In vitro fusion assays
      demonstrated that the TnSNPV F protein induces membrane fusion and syncytia
      formation and were compared to syncytia formed by AcMNPV GP64.

PMID- 15951001
TI  - Phosphate removal and recovery with a synthetic hydrotalcite as an adsorbent.
AB  - Phosphate removal is important to control eutrophication and an ion exchange
      process is one of several treatment processes for this purpose. Hydrotalcite
      compounds (HTALs) are useful as adsorbents for phosphate removal because of their
      ion exchange properties. In this study, the adsorption properties of a granular
      synthetic HTAL for phosphate and the method of regeneration of the granular HTAL
      were examined. The adsorption isotherm of the granular HTAL was approximated by a
      modified Langmuir type, and the maximum adsorption capacity was 47.3 mg P g(-1),
      which corresponded to the content of HTAL in the granular one. Phosphate adsorbed
      on the HTAL was effectively desorbed with alkaline NaCl solutions and the HTAL
      was regenerated with 25 w/v% MgCl(2) solution. The regenerated HTAL could be
      reused repeatedly for the phosphate removal. Phosphate in the exhausted
      desorption solution was recovered as a precipitate of calcium phosphate by
      addition of CaCl(2), and the residual exhausted desorption solution could be also
      reused after supplying NaOH. The results suggest the possibility of an effective
      system for phosphate removal and recovery, which includes the following
      processes: adsorption, desorption, recovery of phosphate, and regeneration of the
      HTAL and the desorption solution.

PMID- 15951002
TI  - Glyphosate adsorption in soils compared to herbicides replaced with the
      introduction of glyphosate resistant crops.
AB  - Use of glyphosate resistant crops was helpful in addressing observed increases in
      environmental contamination by herbicides. Glyphosate is a broad-spectrum
      herbicide, and its behaviour-as well as that of other herbicides-in soils is an
      important consideration for the overall environmental evaluation of genetically
      resistant crop introduction. However, few data have been published comparing
      glyphosate behaviour in soil to that of the herbicides that would be replaced by
      introduction of glyphosate resistant crops. This work compares glyphosate
      adsorption in soil with that of other herbicides frequently used in rape
      (trifluralin and metazachlor), sugarbeet (metamitron) and corn (sulcotrione).
      Herbicide adsorption was characterised in surface soils and in the complete soils
      profiles through kinetics and isotherms using batch equilibration methods.
      Pedological and molecular structure factors controlling the adsorption of all
      five herbicides were investigated. Glyphosate was the most strongly adsorbed
      herbicide, thus having the weakest potential for mobility in soils. Glyphosate
      adsorption was dependent on its ionisable structure in relation to soil pH, and
      on soil copper, amorphous iron and phosphate content. Trifluralin adsorption was
      almost equivalent to glyphosate adsorption, whereas metazachlor, metamitron and
      sulcotrione adsorption were lower. Trifluralin, metazachlor and metamitron
      adsorption increased with soil organic carbon content. Sulcotrione was the least
      adsorbed herbicide in alkaline soils, but its adsorption increased when pH
      decreased. Ranking the adsorption properties among the five herbicides,
      glyphosate and trifluralin have the lowest availability and mobility in soils,
      but the former has the broadest spectrum for weed control.

PMID- 15951003
TI  - Degradation of 4-chlorophenol by microwave irradiation enhanced advanced
      oxidation processes.
AB  - In this work the synergistic effects of several microwave assisted advanced
      oxidation processes (MW/AOPs) were studied for the degradation of 4-chlorophenol
      (4-CP). The efficiencies of the degradation of 4-CP in dilute aqueous solution
      for a variety of AOPs with or without MW irradiation were compared. The results
      showed that the synergistic effects between MW and H2O2, UV/H2O2, TiO2
      photocatalytic oxidation (PCO) resulted in a high degradation efficiency for 4
      CP. The potential of MW/AOPs for treatment of industrial wastewater is discussed.

PMID- 15951004
TI  - Effect of aging on intracellular distribution of abasic (AP) endonuclease 1 in
      the mouse liver.
AB  - The abasic (AP) endonuclease (APE1) plays a central role in the base excision
      repair (BER) pathway for repairing oxidatively damaged bases and abasic sites in
      mammalian genomes. We have investigated age-dependent changes in APE activity,
      contributed primarily by APE1, in total extracts as well as in nuclear,
      mitochondrial, and cytoplasmic compartments of mouse hepatocytes. The APE1
      protein and mRNA levels did not differ significantly between the livers of 4-mo
      (young), 10-mo (middle-aged), and 20-mo (old) mice, and corresponds with similar
      APE activity. However, we observed a 2-fold increase in specific activity of APE1
      in the nucleus, a 2-fold decrease in the cytoplasm, and a 6-fold increase in the
      mitochondrial matrix of hepatocytes of the old relative to the young animals.
      Surprisingly, in the middle-age animals we observed 30% increase in APE activity
      in the nucleus but 6-fold in the mitochondrial matrix. These results indicate age
      dependent accumulation of APE1 in the nucleus and mitochondria. Such
      redistribution occurred early in the mitochondria during the aging process and
      preferential accumulation of APE in the nucleus was more gradual which may
      reflect distinct levels of oxidative stress in these organelles.

PMID- 15951005
TI  - Effect of mild hypothermia on the thrombolytic efficacy of 120 kHz ultrasound
      enhanced thrombolysis in an in-vitro human clot model.
AB  - INTRODUCTION: Ischemic stroke causes substantial death and disability. Currently,
      recombinant tissue plasminogen activator (rt-PA) is the only FDA approved
      therapy. However, there are dangerous side effects and therapy must start within
      3 h of onset. Therefore, there is interest in adjunctive therapies such as
      ultrasound enhanced thrombolysis (UET) and hypothermia. Recently, transcranial
      ultrasound during rt-PA therapy was shown to improve vessel recanalization. Also
      hypothermia (32-34 degrees C) was shown to be safe and possibly improve outcome.
      This suggests combining UET and hypothermia to treat ischemic stroke. Little is
      known about the effects of hypothermia on UET, and in-vitro rt-PA efficacy is
      reduced for T<37 degrees C. Here, the effects of hypothermia on UET in in-vitro
      human clot are presented. It is hypothesized that UET efficacy at 33 degrees C is
      less than at 37 degrees C. MATERIALS AND METHODS: Whole blood was drawn from
      volunteers. Clots were made, incubated at 37 degrees C and aged for 2 days for
      maximal lytic resistance. Clots were exposed to human fresh-frozen plasma
      (control), hFFP and rt-PA ([rt-PA]=3.2 microg/ml), hFFP and 120 kHz ultrasound
      (US), and hFFP, rt-PA and ultrasound (UET) at 33 degrees C and 37 degrees C. Clot
      percent mass loss (Deltam) was measured to determine thrombolytic efficacy. Data
      were analyzed using mixed-model analysis of variance. RESULTS AND CONCLUSIONS: US
      and rt-PA independently increased Deltam (3.5+/-1.0% and 5.1+/-0.9% respectively;
      p<0.01) over control. UET increased Deltam an additional 8.1+/-1.3% (p=0.026) The
      effect of temperature on Deltam (-1.6+/-0.7%) was not significant (p=0.09).
      Hypothermia did not reduce UET efficacy in this in-vitro model.

PMID- 15951006
TI  - Paraformaldehyde induces elevation of intracellular calcium and
      phosphatidylserine externalization in platelets.
AB  - Paraformaldehyde fixation of platelets stabilizes surface antigens while altering
      some that are associated with cellular activation. Present experiments show that
      the asymmetric distribution of phosphatidylserine in platelets was especially
      sensitive to paraformaldehyde treatment. It was found that this reagent induced a
      dose- and time-dependent translocation of phosphatidylserine to the membrane
      surface as measured by annexin V binding and flow cytometry. The percent
      phosphatidylserine-positive cells increased from about 5% to >90%. Chelation of
      extracellular Ca(2+) with EGTA partially blocked this translocation.
      Spectrofluorimetric analysis of fluo-3 loaded platelets indicates that
      paraformaldehyde caused a concomitant elevation of intracellular Ca(2+)
      concentrations, [Ca(2+)](i). ATP levels also declined in paraformaldehyde-treated
      cells, suggesting that the rise in [Ca(2+)](i) ensued in part from decreased
      activity of calcium pumps. Previous studies indicate that phosphatidylserine
      externalization arises from Ca(2+)-activated randomization of membrane
      phospholipids and decreased transport of phosphatidylserine from the outer to the
      inner leaflet of the plasma membrane. In light of present results,
      paraformaldehyde fixation is best avoided particularly in studies involving
      platelet apoptosis or activation.

PMID- 15951007
TI  - Remarks on clinical data concerning dietary supplements that affect
      antithrombotic therapy.

PMID- 15951008
TI  - MDMA (ecstasy) effects in pubescent rats: Males are more sensitive than females.
AB  - In Experiment 1, we assessed the effects of 3,4-methylenedioxymethamphetamine
      (MDMA) on locomotor activity in pubescent male and female Long-Evans rats. Thirty
      nine day old rats were injected ip with 10 mg/kg of MDMA (ambient temperature 25
      degrees C) three times at 2 h intervals. Initially, females showed greater
      locomotor activation by the drug than males, however after the second injection,
      males showed greater hyperlocomotion. After the third injection, 3 of 10 females
      and all of the males died. In the surviving females, we observed serotonin
      depletion in cortex and hippocampus, but catecholaminergic markers were
      unaltered. In Experiment 2, male and female rats were repeatedly injected with
      saline or 2, 5 or 10 mg/kg MDMA and body temperature was measured (ambient
      temperature 21.5 degrees C). After the third injection of 10 mg/kg MDMA, the MDMA
      induced hyperthermia was greater in males than in females (about +0.8 degrees C);
      at the lower dose, no difference was observed. Probably because of the lower
      ambient temperature, only 1 female and 2 males succumbed to the MDMA treatment,
      and MDMA induced less serotonin depletion than in the first experiment, with no
      difference between females and males. Thus, pubescent males appear to be more
      sensitive than females to locomotor and hyperpyretic effects of MDMA. This sex
      dependent effect, which is at variance with previously reported dimorphisms in
      psychostimulant effects, is discussed in terms of possible differences in
      dopamine D1 and D2 receptors at pubescence, or other factors related to drug
      metabolism.

PMID- 15951009
TI  - Mesolimbic dopamine drives the diurnal variation in opiate-induced feeding.
AB  - Brain opioid peptides modulate feeding behavior and opiate drugs have powerful
      orexigenic effects in mammals. Recent studies have shown that opiate-induced
      eating depends, though not exclusively, on mu-opioid receptors located in the
      ventral striatum. Here we report that morphine orexigenic effects vary with the
      time of day according to a biphasic pattern. The effects first increase and then
      decrease during the light phase, with the peak effect occurring in the middle of
      this phase. This diurnal profile is shifted toward the dark phase after dopamine
      deafferentation of the ventral striatum. Consequently, the peak effect of
      morphine is delayed and occurs just before the dark phase. This finding suggests
      that mesolimbic dopamine transmission contributes to the neural mechanisms that
      normally drive the circadian timing of opioid-dependent feeding.

PMID- 15951010
TI  - Heat shock reduces developmental competence and alters spindle configuration of
      bovine oocytes.
AB  - Heat shock may enhance the thermotolerance of, or cause detrimental effects on, a
      variety of cell types or organisms, depending on the duration and intensity of
      the thermal challenge. Experiments were designed to investigate the effect of
      heat shock on the developmental competence and cytoskeletal structures of bovine
      oocytes following IVF. In Experiment 1, bovine cumulus-oocyte complexes (COCs)
      were subjected to standard IVM culture conditions for 20 h and were then randomly
      allocated to groups for heat shock at 42 degrees C for 0 (control), 1, 2, or 4h.
      The oocytes were fertilized after heat shock and followed by culture in KSOM for
      8d. There were no significant differences in cleavage rates, but blastocyst
      formation (27% versus 44%) and total cell number per blastocyst (82+/-21 versus
      108+/-36; mean+/-S.D.) were lower in the 4-h heat shock group compared to the
      control (P<0.05). Trophectoderm, but not ICM, cell numbers were decreased
      (P<0.05) in the 4-h heat shock group compared to the control. Alterations in the
      meiotic spindle of IVM oocytes (n=120-126) were examined after 1 to 4-h of heat
      shock in Experiments 2 and 3. The metaphase spindle became elongated or aberrant
      and smaller following heat shock, compared to the non-heat shock oocytes
      (P<0.05). The basis for changes in spindle configuration and the differential
      decrease in trophectoderm cell numbers after heat shock are not clear, but may
      lead to reduced embryonic development and perhaps the low pregnancy rate of
      domestic animals during hot seasons.

PMID- 15951012
TI  - Vitrification assays with embryos from a cold tolerant sub-arctic fish species.
AB  - Pseudopleuronectes americanus is a Northern teleost species that produces
      antifreeze proteins (AFPs) to protect them from freezing during the winter. These
      AFPs bind to ice crystals to inhibit their growth, and they also protect cell
      membranes at low temperatures. In this study, vitrification trials were done with
      fish embryos at three different developmental stages, using two different
      protocols for incorporating the vitrifying solutions. Toxicity of the
      cryoprotectants and permeability to dimethyl sulfoxide were analyzed. Embryos
      were vitrified in 0.5 ml straws by direct immersion in liquid nitrogen, and their
      morphology and development analyzed following thaw. The embryos responded well to
      vitrification as evidenced by the high percentage that exhibited good morphology
      following thaw. Although none of the embryos hatched, a small percentage (0.92%)
      of them showed active movements within the chorion and continued to develop for a
      number of days following thaw. This is the first record of post-thaw development
      of vitrified fish embryos.

PMID- 15951011
TI  - Developmental changes of heat-shock proteins in porcine testis by a proteomic
      analysis.
AB  - Heat-shock proteins (HSPs) are important in spermatogenesis. This study
      investigated developmental changes in the expression of major HSPs in porcine
      testis. The testis from five immature (mean age 2.9+/-0.1 months) and five mature
      boars (35.7+/-14.0 months) were examined. Two-dimensional polyacrylamide gel
      electrophoresis was conducted and proteins were identified by Western blotting
      and/or matrix-assisted laser desorption/ionization mass spectrometry. Moreover,
      the 90, 70, and 60 kDa HSPs, 70 kDa heat-shock cognate protein (HSC 70), tubulin,
      and actin were quantified on two-dimensional gels. Protein spots were quantified
      by densitometry, combined with a computer-assisted image analysis system.
      Immunohistochemistry was performed to analyze the expression pattern of major
      HSPs and beta-tubulin in testis. One isoform of HSP 90 (HSP 90 alpha), two
      isoforms of HSC 70 (HSC 70a and HSC 70c), one isoform of HSP70 (HSP 70e), and
      tubulin increased after sexual maturation (P<0.05). A testis-specific HSP70
      (P70t) was markedly increased in the testes of sexually mature boars. Meanwhile,
      levels of actin and some isoforms of HSPs including 60 kDa HSP remained similar
      in both groups. These observations were further confirmed by
      immunohistochemistry; therefore, the upregulation of protein expression in the
      adult testis could be attributed to a higher level of protein expression and the
      number of cells that were HSPs-positive already resided in the immature testis.
      The differential expression of major HSPs suggested that they may be important in
      porcine spermatogenesis.

PMID- 15951013
TI  - Colloidal gold nanoparticle modified carbon paste interface for studies of tumor
      cell adhesion and viability.
AB  - A non-toxic biomimetic interface for immobilization of living cells and
      electrochemical exogenous effect study of cell viability was constructed by
      mixing colloidal gold nanoparticles in carbon paste. A new approach to study the
      effects of anti-tumor drug and other exogenous factors on cell viability was
      proposed. The nanoparticles were efficient for preserving the activity of
      immobilized living cells and preventing their leakage from the electrode surface.
      The immobilized living AsPC-1 cells (pancreatic adenocarcinoma cells derived from
      ascites) exhibited an irreversible voltammetric response related to the oxidation
      of guanine. The presence of guanine was verified by liquid chromatography-mass
      spectrometry. The contents of guanine in cytoplasm of each AsPC-1 and normal
      pancreatic cell were detected to be 370 and 22amol, respectively. The cytotoxic
      effect of adriamycin resulted in a decrease in peak current of guanine. The
      optimal exogenous factors that affected cell viability, including pH, temperature
      and salt concentration of electrolyte, were just consistent with cell growth
      conditions in culture. This simple and rapid method could be applied for the
      electrochemical investigation of exogenous effect and characterization of the
      viability of living cells.

PMID- 15951014
TI  - Hollow gold nanoparticles encapsulating horseradish peroxidase.
AB  - Hollow nanoshells of gold entrapping an enzyme, horseradish peroxidase (HRP), in
      the cavity of the nanoshell have been prepared in the reverse micelles by
      leaching out silver chloride (AgCl) from Au(shell)AgCl(core) nanoparticles with
      dilute ammonia solution. The particles have been characterised by dynamic laser
      light scattering (DLS), transmission electron microscopy (TEM), X-ray diffraction
      (XRD), and electron diffraction. The particle size is below 100 nm diameter,
      depending upon the size of the aqueous core of reverse micelles in which these
      particles have been prepared. This soft-chemical method for the preparation of
      such particles allows the entrapped enzyme to remain active inside the hollow
      gold nanoparticles. Small substrate molecules such as o-dianisidine can easily
      enter through the pores of the nanoshell and can undergo enzymatic oxidation by
      H2O2. The enzyme kinetics follows Michaelis-Menten mechanism. When the substrate
      is chemically conjugated with dextran molecule (10 kDa), the enzymatic reaction
      is practically completely prevented perhaps by the inability of dextran-o
      dianisidine conjugate to penetrate the pores of the nanoshells. However, HRP did
      not show any activity when trapped inside solid gold nanoparticles.

PMID- 15951015
TI  - HtrA3, a serine protease possessing an IGF-binding domain, is selectively
      expressed at the maternal-fetal interface during placentation in the mouse.
AB  - Hemochorial placentation involves highly regulated interactions between fetal-
      and maternal-derived cells. HtrA3, a novel serine protease containing an insulin
      like growth factor (IGF) binding domain, was previously shown to increase during
      early pregnancy in the mouse uterus, being dramatically upregulated post
      implantation. The present study examined the regulation of HtrA3 gene in the
      mouse uterus from post-implantation to late gestation. Both mRNA and protein of
      HtrA3 were localized specifically in the maternal decidua. In contrast, HtrA3
      expression was below detection in trophoblasts, including the giant cells that
      are in direct contact with the decidua. This pattern persisted from the early
      stages of placentation to near term. The level of decidual HtrA3 mRNA and its
      protein gradually decreased as the placenta matured. In the decidua, only the
      maternal decidual cells, but not blood vessels or uterine NK cells that are
      present in large numbers, were positive for HtrA3. The specific localization of a
      protease possessing an IGF-binding domain at the maternal-fetal interface
      suggests that HtrA3 plays a critical role in mediating maternal decidual
      remodelling and maintenance, likely in association with the IGF system, in
      placental development and function.

PMID- 15951016
TI  - Comparison of pregnancy course and outcome with color and radiographic
      angiography of the placenta in a monochorionic triplet pregnancy.
AB  - A patient with spontaneous monochorionic (MC) triamniotic triplet pregnancy
      developed symptoms of feto-fetal-transfusion-syndrome (FFTS) at 18 weeks of
      gestation with one donor (oligohydramnios) and one receptor (polyhydramnios)
      triplet. The patient "received" a diet enriched with proteins. Amniotic-fluid
      volume returned to normal after 24 weeks. At 32 weeks, a Cesarean section was
      performed due to intra-uterine growth restriction of the donor triplet. Post
      partum color injection and computer angiograms showed arterio-arterial (AA)
      anastomoses between all triplets. Deep arterio-venous (AV) anastomoses between
      the two triplets who had demonstrated with oligo- and polyhydramnios between 18
      and 26 weeks were revealed by computer angiography that were not seen by
      placental color angiogram. Detailed analysis of placental vascular communications
      by use of color injection angiogram of the chorionic plate and computer angiogram
      demonstrating deep anastomoses beneath the chorionic plate helps to understand
      the individual pathophysiology and clinical course in patients with FFTS, which
      is even more complex in MC triplet compared to MC twin pregnancies.

PMID- 15951017
TI  - Synthesis and characterization of binuclear molybdenum-polycarboxylate complexes
      with sulfur bridges.
AB  - A group of four binuclear sulfur-bridged molybdenum-polycarboxylato complexes
      with homocitrate, citrate, cysteine, ethylenediaminetetraacetate ligands,
      respectively, have been synthesized and characterized. These complexes were
      prepared in order to study the interaction of Mo and homocitrate in the FeMo-co
      of nitrogenases. In the structures of K4(NH4)2[Mo2O2S2(C6H4O7)2].10H2O (2),
      (NH4)2[Mo2O2S2(C3H5SNO2)2].5H2O (3) and (NH4)2[Mo2O2S2(C10H12N2O8)].3.5H2O (4),
      molybdenum (V) atom adopts a distorted octahedral arrangement through a terminal
      oxygen atom, two bridging sulfur atoms and three atoms from the ligand (hydroxyl,
      alpha-, beta-carboxylates, sulfide or amine). The coordination mode of
      homocitrate ligand in K5(NH4)[Mo2O2S2(C7H5O7)2].3H2O.CH3OH (1) has been proposed
      in a tridentate fashion via its hydroxyl and a pair of carboxylate groups (alpha
      , beta-carboxylates). The electrochemical properties of these complexes have been
      discussed.

PMID- 15951018
TI  - Mixed cryoglobulinemia with renal failure, cutaneous vasculitis and peritonitis
      due to Brucella melitensis.
AB  - Cryoglobulinemia has been described in infectious diseases, but in only three
      patients with brucellosis. We report a 59-year-old male with Brucella peritonitis
      with cutaneous vasculitis and renal failure that could be related to mixed
      cryoglobulinemia. As in cryoglobulinemia associated with other infections,
      resolution of the disease was obtained with specific antimicrobial therapy.

PMID- 15951019
TI  - Vogt-Koyanagi-Harada disease associated with interferon-A and ribavirin therapy
      for chronic hepatitis C infection.
AB  - A rare case of Vogt-Koyanagi-Harada disease associated with ribavirin and
      interferon-alpha treatment for chronic hepatitis C infection is presented. The
      potential role of interferon and/or ribavirin therapy is discussed. Physicians
      should be aware of the association between interferon-alpha and ribavirin use for
      hepatitis C infection and the development of Harada's disease. Close monitoring
      of such patients for ocular side effects is necessary.

PMID- 15951020
TI  - The role of Rho GTPases and SNAREs in mediator release from granulocytes.
AB  - Granulocytes are defined as the population of granulated white blood cells
      (eosinophils, neutrophils, and basophils). These cells are involved in
      inflammation and contribute to the pathogenesis of allergic and inflammatory
      diseases. Inflammation is induced by the release of mediators from granulocytes
      recruited to or resident within tissues, resulting in edema, leukocyte
      recruitment, and tissue injury. Eosinophils and neutrophils express Rac1 and Rac2
      guanosine triphosphatases (GTPases), 2 members of the Rho GTPase subfamily of ras
      related GTPases. Rho GTPases are activated by receptors in the cell membrane and
      are proposed to function as intracellular molecular switches to regulate mediator
      release, including exocytosis, from granulocytes. Exocytosis involves granule
      fusion, which requires the binding of intracellular membrane receptors known as
      SNAP receptor (SNAREs; soluble N-ethylmaleimide-sensitive factor [NSF] attachment
      protein [SNAP] receptors). Eosinophils and neutrophils express similar SNARE
      isoforms that are important in granule fusion events. Together, these molecules
      link together to form a common signaling pathway for mediator release from
      granulocytes. Identifying these molecules and their function may provide novel
      targets for the prevention of inflammatory reactions.

PMID- 15951021
TI  - Abnormal ryanodine receptor function in heart failure.
AB  - The abnormally regulated release of Ca2+ from an intracellular Ca2+ store, the
      sarcoplasmic reticulum (SR), is the mechanism underlying contractile and
      relaxation dysfunctions in heart failure (HF). According to recent reports,
      protein kinase A (PKA)-mediated hyperphosphorylation of ryanodine receptor (RyR)
      in the SR has been shown to cause the dissociation of FK506 binding protein
      (FKBP) 12.6 from the RyR in heart failure. This causes an abnormal Ca2+ leak
      through the Ca2+ channel located in the RyR, leading to an increase in the
      cytosolic Ca2+ during diastole, prolongation of the Ca2+ transient, and
      delayed/slowed diastolic Ca2+ re-uptake. More recently, a considerable number of
      disease-linked mutations in the RyR have been reported in patients with
      catecholaminergic polymorphic ventricular tachycardia (CPVT) or arrhythmogenic
      right ventricular dysplasia type 2. An analysis of the disposition of these
      mutation sites within well-defined domains of the RyR polypeptide chain has led
      to the new concept that interdomain interactions among these domains play a
      critical role in channel regulation, and an altered domain interaction causes
      channel dysfunction in the failing heart. The knowledge gained from the recent
      literature concerning the critical proteins and the changes in their properties
      under pathological conditions has brought us to a better position to develop new
      pharmacological or genetic strategies for the treatment of heart failure or
      cardiac arrhythmia. A considerable body of evidence reviewed here indicates that
      abnormal RyR function plays an important role in the pathogenesis of heart
      failure. This review also covers some controversial issues in the literature
      concerning the involvement of phosphorylation and FKBP12.6.

PMID- 15951022
TI  - FTY720, a new class of immunomodulator, inhibits lymphocyte egress from secondary
      lymphoid tissues and thymus by agonistic activity at sphingosine 1-phosphate
      receptors.
AB  - FTY720 is the first of a new immunomodulator class: sphingosine 1-phosphate (S1P)
      receptor agonist. In 1994, an immunosuppressive natural product, ISP-I
      (myriocin), was isolated from the culture broth of Isaria sinclairii, a type of
      vegetative wasp. The chemical modification of ISP-I yielded a new compound,
      FTY720, which has more potent immunosuppressive activity and less toxicity than
      ISP-I does. FTY720 has been shown to be highly effective in experimental
      allotransplantation models and autoimmune disease models. A striking feature of
      FTY720 is the induction of a marked decrease in peripheral blood T- and B-cells
      at doses that show immunosuppressive activity in these models. Reportedly, FTY720
      is rapidly converted to FTY720-phosphate (FTY720-P) by sphingosine kinase 2 in
      vivo, and FTY720-P acts as a potent agonist at S1P receptors. Recently, it has
      been suggested that FTY720-P internalizes S1P1 on lymphocytes and thereby
      inhibits the migration of lymphocytes toward S1P. Thus, it is likely that the
      reduction of circulating lymphocytes by FTY720 is due to the inhibition of
      S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus.
      Because FTY720 displays a novel mechanism of action that has not been observed
      with other immunosuppressive agents and shows a synergism with cyclosporin A
      (CsA) and tacrolimus, it is presumed that FTY720 provides a useful tool for the
      prevention of transplant rejection and a new therapeutic approach for autoimmune
      diseases including multiple sclerosis and rheumatoid arthritis.

PMID- 15951023
TI  - Does the isthmic organizer influence D/V patterning of the midbrain?
AB  - Early brain and spinal cord regionalization along the dorsoventral axis are
      thought to be governed by similar mechanisms. Subsequently, the size of the alar
      plate of the neural tube increases dramatically in the midbrain and anterior
      forebrain, compared to the spinal cord. This suggests that additional mechanisms
      may be required to refine A/P and D/V patterning in these structures. The isthmic
      organizer is a signaling center that controls both growth and patterning in the
      midbrain and anterior hindbrain through the production of several secreted
      molecules, in particular FGF8. Several studies have indicated that the isthmic
      organizer is involved in the positioning and development of the midbrain roof and
      floor plates, the two structures that respectively mark the dorsal and ventral
      axis of the neural tube. It remains unclear whether its influence on axis
      formation in the midbrain is a consequence of a more general function of the
      isthmic organizer/FGF8 as a modulator of DV patterning or if selection of an axis
      is a necessary and general by-product of its organizing function not directly
      related to D/V patterning. In this paper, we review the current data supporting
      each possibility.

PMID- 15951024
TI  - Different activation patterns of proinflammatory cytokines in melancholic and non
      melancholic major depression are associated with HPA axis activity.
AB  - BACKGROUND: Recent studies showed an activation of the cytokine system and the
      HPA axis in major depression, although with inconsistent results. While the non
      melancholic subtype displayed a proinflammatory cytokine pattern, the melancholic
      subtype showed signs of impaired cytokine production. In order to understand the
      potential pathogenic significance of these systems further, the interplay between
      the cytokine system and the HPA axis in depressive subtypes as well as potential
      changes of these systems during the course of disease were investigated. METHODS:
      N=37 initially unmedicated patients with acute major depression were sub
      classified (melancholic vs. non-melancholic) and compared with N=37 matched
      healthy controls. Upon admission and after complete clinical remission, basal
      plasma ACTH and serum cortisol levels as well as cytokine productions (IL-1beta,
      IL-1 receptor antagonist (IL-1RA)) upon mitogen stimulation (PHA) were measured
      in a whole blood assay. RESULTS: ACTH and cortisol concentrations were
      significantly elevated on admission in the melancholic but not the non
      melancholic subgroup. Non-melancholic patients produced significantly more IL
      1beta and IL-1RA upon admission than controls or melancholic patients. The IL-1
      RA/IL-1beta ratio was significantly lower in the non-melancholic compared to the
      melancholic subgroup and increased significantly upon remission. LIMITATIONS:
      Patient treatment was not standardized. No Dex/CRH test was performed.
      CONCLUSIONS: Melancholic patients demonstrated an activation of the HPA axis in
      acute stage with partial normalization upon remission but no signs of
      inflammation. Non-melancholic patients showed signs of inflammation in acute
      depression with normalization upon remission while the function of the HPA axis
      was normal.

PMID- 15951025
TI  - The neutralizing epitope ELDKWA on HIV-1 gp41: genetic variability and
      antigenicity.
AB  - Viral evasion through mutations of neutralizing epitopes is a major challenge to
      AIDS vaccine development and clinical therapy. In this study, we analyzed the
      genetic variability of principal neutralizing epitope ELDKWA among 5393 HIV
      isolates in the HIV sequence database (). It has been found that six out of seven
      frequent variants were able to cause the invalidation of famous neutralizing MAb
      2F5. Moreover, escape mutations K665S and K665E, often observed in C-subtype and
      O-group strains, respectively, were reported more frequently in recent years.
      Furthermore, we studied the antigenicity of these variants. Polyclonal antibodies
      induced by a candidate multi-epitope-vaccine were able to react with the
      recombinant gp41, respectively, carrying these variants, indicating that "epitope
      cocktail" strategy is necessary and helpful in vaccine design.

PMID- 15951026
TI  - Chiasmatic neurons in the ventral diencephalon of mouse embryos--changes in
      arrangement and heterogeneity in surface antigen expression.
AB  - We have investigated the changes in arrangement of the SSEA-1 immunoreactive
      chiasmatic neurons in the mouse ventral diencephalon from embryonic day (E) 9 to
      the end of gestation. A regionally specific staining of SSEA-1 was first detected
      in the ventricular layer of the caudal diencephalon at E10 and later at E11 on
      the cells in the subventricular layer. At E12, these cells formed the
      characteristic V-shaped configuration caudal to the optic axons in the chiasm. At
      E13-E15, this neuronal array changes gradually to a configuration that
      facilitates contact with the optic axons only at the midline and the initial
      segment of the optic tract. Colocalization studies showed that CD44 was localized
      strongly on the neurons in the central but not lateral domains of the array,
      suggesting existence of heterogeneity in these neurons in terms of surface
      antigen presentation. This difference between the central and lateral domains
      raises the possibility that the chiasmatic neurons may regulate the patterning of
      axon orders at the midline and the optic tract through presentation of distinct
      combination of guidance cues at these strategic positions in the optic pathway.
      Furthermore, exogenous Lewis-x/SSEA-1 inhibited neurite outgrowth from the E14
      retinal explants; this inhibition was observed in neurites from both ventral
      temporal and dorsal nasal retina. These findings suggest an action of this
      surface carbohydrate on the control of axon growth and guidance in the mouse
      optic pathway.

PMID- 15951027
TI  - Anti-TNF-alpha reduces the inflammatory reaction associated with cuff electrode
      implantation around the sciatic nerve.
AB  - Extraneural cuff electrodes have been extensively used to investigate the nervous
      system. Their implantation is, however, associated with epineurial fibrosis,
      fiber loss, limited reproducibility of recordings and variability in stimulating
      conditions. It has recently been shown that TNF-alpha is involved in nerve
      alterations after electrode implantation. This study investigated whether a peri
      operative anti-TNF-alpha treatment could modify the inflammation and fibrosis
      associated with cuff electrode implantation. Morphometrical and
      immunohistochemical methods were used to show that a single systemic injection of
      TNF-alpha neutralizing antibodies is sufficient to reduce the early inflammatory
      events, but not the long lasting fibrotic reaction.

PMID- 15951028
TI  - Lord of the rings--the mechanism for oxidosqualene:lanosterol cyclase becomes
      crystal clear.
AB  - The enzyme oxidosqualene:lanosterol cyclase (OSC) represents a novel target for
      the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the
      linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol
      intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the
      formation of 24(S),25-epoxycholesterol, a ligand activator of the liver X
      receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively
      enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC
      inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol
      and prevents cholesterol deposition within macrophages. The recent
      crystallization of OSC identifies the mechanism of action for this complex
      enzyme, setting the stage for the design of OSC inhibitors with improved
      pharmacological properties for cholesterol lowering and treatment of
      atherosclerosis.

PMID- 15951029
TI  - A human immunodeficiency virus type 1 protease biosensor assay using
      bioluminescence resonance energy transfer.
AB  - A sensitive reporter assay to measure human immunodeficiency virus type 1 (HIV-1)
      protease (PR) activity is described in this manuscript. This assay measures PR
      activity as a function of the resonance energy transfer (RET) between a donor
      molecule [humanized sea pansy Renilla reniformis luciferase (hRLuc)] and an
      energy acceptor molecule, humanized green fluorescent protein (hGFP2) when
      expressed in mammalian cells. This is a naturally occurring phenomenon and is an
      emerging and powerful technology that has significant advantages over alternative
      in vitro PR assays. The HIV-1 Gag-p2/Gag-p7 (p2/p7) PR site was inserted between
      hGFP2 and hRLuc. The newly created vector, hRLuc-p2/p7-hGFP2 was co-expressed
      with an HIV-1 codon-optimized PR+ or PR- Gag/Pol expressor. Expression of the
      hRLuc-p2/p7-hGFP2 alone or with the PR- Gag-Pol expressor generated a BRET2
      indicating that the PR cleavage site was not cleaved, whereas the inclusion of
      the PR+ Gag-Pol produced a significant reduction in the BRET2. The inclusion of
      PR inhibitors Saquinavir or Amprenavir, or the expression of a p2/p7 PR substrate
      mutant also blocked the cleavage to result in a stable BRET2 signal. Because the
      HIV-1 auxiliary protein Vif has been shown to modulate the HIV-1p2/p7 cleavage,
      this assay was then validated in studies in which Vif was expressed. When Vif was
      overexpressed along with hRLuc-p2/p7-hGFP2 and PR+ Gag-Pol, the decrease in BRET2
      was abrogated in a dose-dependent manner, demonstrating that supraphysiologic
      levels of Vif block p2/p7 cleavage. An accumulation of a Gag processing
      intermediate was observed, indicating that p2/p7 cleavage was negatively
      affected. Overexpression of an RNA-binding-defective Staufen protein or a related
      dsRNA-binding protein TRBP had no effect on PR cleavage activity as shown by
      Western and BRET2 analyses. The p2/p7 processing data were confirmed by Western
      blot analyses. BRET is non-invasive and occurs within live cells, is measured in
      real time, and is not restricted to cellular compartments making it an especially
      attractive technology to identify small bioactive inhibitory molecules. This PR
      BRET2 biosensor assay can be adapted for high throughput screening of new HIV-1
      PR inhibitors. It can be employed to screen for antiviral compounds that also
      target the proteases of other viruses.

PMID- 15951030
TI  - A multiplex polymerase chain reaction method for reliable, sensitive and
      simultaneous detection of multiple viruses in citrus trees.
AB  - A multiplex polymerase chain reaction (mPCR) assay was developed to detect six
      RNA and one DNA citrus virus: Citrus leaf rugose virus (CLRV), Citrus psorosis
      virus (CPsV), Citrus tatter leaf virus (CTLV), Citrus tristeza virus (CTV),
      Citrus variegation virus (CVV), Citrus yellow mosaic virus (CYMV), and Indian
      citrus ringspot virus (ICRSV) from citrus plants. These seven viruses are
      classified in six different virus genera. Degenerate primers were designed based
      on the respective virus isolate sequence data available from the GenBank and were
      used for reliable detection of the different viruses by simplex- and mPCR. The
      sensitive and simultaneous detection of RNA and DNA viruses using the mPCR
      decreases the risk of contamination, saves time and reduces the cost as compared
      to other conventional methods for citrus virus detection. Seven different
      fragments (245-942 bp) specific to the viruses were simultaneously amplified
      using mPCR and were identified on the basis of their molecular sizes. The
      consistent results of the mPCR were compared with simplex PCR for detection of
      each virus pathogen. The mPCR results were confirmed with sequencing analysis.
      The mPCR provides a useful rapid method for detecting multiple viruses in citrus
      plants that will aid in the production of virus-free citrus plants for
      certification programs.

PMID- 15951031
TI  - Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A
      receptors.
AB  - Estrogen deficiency has been associated with stress, anxiety and depression.
      Estrogen receptors have been identified in the median raphe nucleus (MRN). This
      structure is the main source of serotonergic projections to the hippocampus, a
      forebrain area implicated in the regulation of defensive responses and in the
      resistance to chronic stress. There is evidence showing that estrogen modulates 5
      HT1A receptor functions. In the MRN, somatodendritic 5-HT1A receptors control the
      activity of serotonergic neurones by negative feedback. The present study
      evaluated the effect of intra-MRN injection of estradiol benzoate (EB) (600 or
      1200ng/0.2microl) on the performance of ovariectomised rats submitted to the
      elevated plus-maze test of anxiety and to the open-field test. Additionally, the
      same effect was evaluated with a previous intra-MRN injection of WAY
      100635(100ng/0.2microl), an antagonist of 5-HT1A receptors. The results showed
      that both doses of EB increased the percentage of entries and the percentage of
      time spent into the open arms, suggestive of an anxiolytic effect. The highest
      dose of the drug also increased the number of entries into the enclosed arm and
      locomotion in the open field, indicating a stimulatory motor effect. WAY 100635
      antagonised the effect of estradiol in the elevated plus-maze and in the open
      field. The results show that estrogen receptors of the MRN are implicated in the
      regulation of anxiety-related behaviour. The results also support claims that the
      effect of estrogen involves a change in 5-HT1A receptor function.

PMID- 15951032
TI  - Galantamine-induced behavioral recovery after sublethal excitotoxic lesions to
      the rat medial septum.
AB  - Clinical trials show beneficial effects of acetylcholinesterase (AChE)
      inhibitors, including galantamine, on cognitive functions in patients with mild
      to moderate Alzheimer's disease. Galantamine shows a dual action profile by also
      acting as an allosteric modulator of nicotinic acetylcholine receptors.
      Nevertheless, its in vivo mechanism of action is only partly understood. Here, we
      first established a novel lesion model provoking significant functional
      impairment of the septo-hippocampal projection system without triggering massive
      neuronal death in the rat medial septum. Next, we studied whether galantamine,
      administered in doses of 1 and 3mg/kg post-lesion, promotes functional recovery
      of spatial navigation behaviors, and affects the output of septal cholinergic
      projections. Infusion of N-methyl-d-aspartate (NMDA; 30nmol/1microl) in the
      medial septum resulted in spatial learning deficits associated with significant
      shrinkage of cholinergic neurons and reduced AChE activity in the hippocampus at
      7 days post-lesion. Galantamine treatment alone significantly increased the
      hippocampal acetylcholine concentration and attenuated the NMDA-induced spatial
      learning impairment. Galantamine post-treatment also affected NMDA-induced
      changes in AChE and choline-acetyltransferase activities. In conclusion, our data
      show that galantamine attenuates experimentally-induced cognitive impairments
      underscored by mild neuronal damage.

PMID- 15951033
TI  - Influence of container adsorption upon observed pyrethroid toxicity to
      Ceriodaphnia dubia and Hyalella azteca.
AB  - Pyrethroid insecticides are known for their potential toxicity to aquatic
      invertebrates and many fish species. A significant problem in the study of
      pyrethroid toxicity is their extreme hydrophobicity. They can adsorb to test
      container surfaces and many studies, therefore, report pyrethroid levels as
      nominal water concentrations. In this study, pyrethroid adsorption to sampling
      and test containers was measured and several container treatments were examined
      for their ability to decrease pyrethroid adsorption. None of the chemical
      treatments were successful at preventing pyrethroid loss from aqueous samples,
      but vortexing of containers served to resuspend pyrethroids. The effects of the
      observed adsorption on Ceriodaphnia dubia and Hyalella azteca permethrin toxicity
      were examined. Species-specific results showed a time-dependent decrease in
      toxicity following pyrethroid adsorption to test containers for C. dubia, but not
      for H. azteca. These results demonstrate that pyrethroid adsorption to containers
      can significantly affect the observed outcome in toxicity-testing and serves as a
      caution for researchers and testing laboratories.

PMID- 15951034
TI  - Function of the plasmodium export element can be blocked by green fluorescent
      protein.

PMID- 15951036
TI  - Growth factor receptors, lipid rafts and caveolae: an evolving story.
AB  - Growth factor receptors have been shown to be localized to lipid rafts and
      caveolae. Consistent with a role for these cholesterol-enriched membrane domains
      in growth factor receptor function, the binding and kinase activities of growth
      factor receptors are susceptible to regulation by changes in cholesterol content.
      Furthermore, knockouts of caveolin-1, the structural protein of caveolae, have
      confirmed that this protein, and by implication caveolae, modulate the ability of
      growth factor receptors to signal. This article reviews the findings pertinent to
      the relationship between growth factor receptors, lipid rafts and caveolae and
      presents a model for understanding the disparate observations regarding the role
      of membrane microdomains in the regulation of growth factor receptor function.

PMID- 15951035
TI  - Genes coding for SecG and Leu2-tRNA form an operon to give an unusual RNA
      comprising mRNA and a tRNA precursor.
AB  - The secG gene encoding the SecG subunit of the SecYEG translocon and the leuU
      gene encoding Leu2-tRNA are very closely located on the Escherichia coli
      chromosome. A secG-leuU disruptant was not viable unless secG-leuU was induced
      from a plasmid, indicating that leuU is an essential gene since secG is
      dispensable at 37 degrees C. A mutant strain in which the promoter region for
      secG was replaced with cat revealed the same phenotype as the secG-leuU
      disruptant, indicating that leuU was expressed from the secG promoter. When the
      secG-leuU locus was placed on a high copy plasmid, an RNA comprising both mRNA
      for SecG and a precursor for Leu2-tRNA was detected on a Northern blot. Moreover,
      a secG-leuU transcript was amplified by RT-PCR using the total RNA fraction
      prepared from wild type E. coli cells but not from the secG-leuU and the secG
      promoter disruptants, indicating that secG-leuU forms an operon. Thus, the
      expression of Leu2-tRNA requires expression of the upstream secG gene. The gene
      structure of secG-leuU was conserved among Gram-negative bacteria, although the
      sequences separating the two genes were quite diverse. The physiological
      significance of this unusual gene organization is discussed.

PMID- 15951037
TI  - Escherichia coli O157 prevalence in Dutch poultry, pig finishing and veal herds
      and risk factors in Dutch veal herds.
AB  - In the period October 1996 through December 2000, a total of 7163 pooled faecal
      samples of laying hen and broiler flocks, finishing-pig herds and veal herds were
      examined for the presence of Salmonella spp., Campylobacter spp. and
      verocytotoxin-producing Escherichia coli O157 as part of a national monitoring
      programme in The Netherlands. Isolates were tested for eae and VT genes. Risk
      factors for Dutch veal herds were quantified. For all herd/flock types, faecal
      samples were cultured for E. coli O157. Of broiler flocks, laying flocks and
      finishing pig herds, respectively, 1.7%, 0.5% and 0.4% were E. coli O157
      positive. In total, 42 of the 454 veal herds (9.3%) showed at least one positive
      pooled sample. E. coli O157-positive herds were compared (with logistic
      regression) to negative herds, regarding variables obtained from the
      questionnaire taken from the farm manager. To account for season, a sine function
      was included in the logistic regression as offset variable. In the final model,
      'pink-veal production' (compared to white-veal production), 'group housing of the
      sampled herd' (compared to individual housing), 'more than one stable present'
      (compared to one stable present), 'hygienic measures regarding visitors'
      (compared to no hygienic measures), 'interval arrival-sampling of a herd of >20
      weeks' (compared to < or =10 weeks), and 'presence of other farms within 1 km'
      (compared to no presence of farms <1 km) showed associations (P<0.05) with the
      presence of E. coli O157. These results need careful interpretation; they should
      be considered as indications for further (experimental or cohort-based) research
      rather then causal associations.

PMID- 15951038
TI  - A new source of endothelial progenitor cells--vascular biology redefined?
AB  - The initial discovery of endothelial progenitor cells (EPCs) in tandem with
      emerging concepts in stem cell biology has generated enormous interest and
      excitement in fields as diverse as tissue engineering, regenerative medicine, and
      tumor and vascular biology. A recent paper by Ingram et al. identifies a complete
      hierarchy of EPCs in the vessel wall, providing a new framework for
      classification of cells supporting endopoiesis akin to that previously
      established for hematopoiesis. This could have fundamental implications for our
      understanding of the role of the endothelium and, more specifically, the role of
      EPC interfacing with the vessel wall in health and disease.

PMID- 15951039
TI  - Cloning, expression and characterisation of Erwinia carotovora L-asparaginase.
AB  - Bacterial L-asparaginases (E.C. 3.5.1.1) have been used as therapeutic agents in
      the treatment of acute childhood lymphoblastic leukaemia. L-asparaginase from
      Erwinia carotovora NCYC 1526 (ErA) was cloned and expressed in E. coli. The
      enzyme was purified to homogeneity by a two-step procedure comprising cation
      exchange chromatography and affinity chromatography on immobilised L-asparagine.
      The enzymatic properties of the recombinant enzyme were investigated and the
      kinetic parameters (K(m), k(cat)) for a number of substrates were determined.
      Molecular modelling studies were also employed to create a model of ErA, based on
      the known structure of the Erwinia chrysanthemi enzyme. The molecular model was
      used to help interpret biochemical data concerning substrate specificity and
      catalytic mechanism of the enzyme. The kinetic parameters of selected substrates
      were determined at various pH values, and the pH-dependence profiles of V(max)
      and V(max)/K(m) were analyzed. The pH-dependence of V(max) shows one transition
      in the acidic pH range with pK(a)=5.4, and the pH-dependence of V(max)/K(m)
      exhibits two transitions with pK(a)=5.4 and 8.5. Based on analysis of alternative
      substrates and molecular modelling studies, it was concluded that the pK(a) at
      the acidic pH range corresponds to the active site residues Asp115 or Glu82,
      whereas the pK(a) observed at the alkaline pH range is not due to substrate amino
      group ionisation, but rather is the result of enzyme ionisation. The effect of
      temperature and viscosity on the catalytic activity of the enzyme was also
      investigated and it was concluded that the rate-limiting step of the catalytic
      reaction is relevant to structural transitions of the protein. Thermodynamic
      analysis of the activity data showed that the activation energies are dependent
      on the substrate, and entropy changes appear to be the main determinant
      contributing to substrate specificity.

PMID- 15951040
TI  - VEGF profiling and angiogenesis in human microtissues.
AB  - Owing to its dual impact on tissue engineering (neovascularization of tissue
      implants) and cancer treatment (prevention of tumor-induced vascularization),
      management and elucidation of vascularization phenomena remain clinical
      priorities. Using a variety of primary human cells and (neoplastic) cell lines
      assembled in microtissues by gravity-enforced self-aggregation in hanging drops
      we (i) studied size and age-dependent VEGF production of microtissues in
      comparison to isogenic monolayer cultures, (ii) characterized the self
      organization and VEGF-production potential of mixed-cell spheroids, (iii)
      analyzed VEGF-dependent capillary formation of human umbilical vein endothelial
      cells (HUVECs) cells coated onto several human primary cell spheroids, and (iv)
      profiled endostatin action on vascularization in human microtissues. Precise
      understanding of vascularization in human microtissues may foster advances in
      clinical tissue implant engineering, tumor treatment, as well as drug discovery
      and drug-function analysis.

PMID- 15951041
TI  - Strain development in Bacillus licheniformis: construction of biologically
      contained mutants deficient in sporulation and DNA repair.
AB  - By introducing defined deletions in recA and an essential sporulation gene
      (spoIV), stable mutant strains of Bacillus licheniformis were obtained which are
      totally asporogenous and severely affected in DNA repair, and thus being UV
      hypersensitive. Studies on growth in various liquid media as well as on amylase
      production revealed no differences of the mutants when compared to the wild type.
      Hence, such genes appear to be suitable disruption targets for achieving passive
      biological containment in this industrially exploited species.

PMID- 15951042
TI  - Baculovirus-mediated production of HDV-like particles in BHK cells using a novel
      oscillating bioreactor.
AB  - We have recently demonstrated the assembly of hepatitis delta virus-like
      particles (HDV VLP) by co-transducing hepatoma cells using two recombinant
      baculoviruses, one encoding hepatitis B surface antigen (HBsAg), and one encoding
      large delta antigen (L-HDAg). In this study, we further demonstrated the assembly
      and secretion of VLP in other mammalian cells. The assembly efficiency varied
      depending on cell lines, the baculovirus constructs and the relative dosage of
      both recombinant viruses. The co-transduction of BHK cells led to the formation
      of VLPs resembling authentic virions in size and appearance. The production
      process was transferred to a novel oscillating packed bed bioreactor, BelloCell,
      in which the transduction efficiency was up to approximately 90% for a high cell
      density of 1.5 x 10(7) cells/cm(3) bed and a total yield of 427 microg based on
      HBsAg in the VLP (harvested from 940 ml medium) was obtained. The particle yield
      corresponded to an average volumetric yield of 454 ngml(-1) and a specific yield
      of 285 microg/10(9) cells, and is significantly superior to that can be obtained
      by the commonly employed transfection method. The combination of baculovirus
      transduction and BelloCell reactor, thus, may represent a simple and efficient
      approach for the production of HDV VLP and viral vectors.

PMID- 15951043
TI  - Towards an understanding of the molecular basis of herpes simplex virus latency.
AB  - The survival strategy of herpes simplex virus centres on the establishment of
      latency in sensory neurons innervating the site of primary infection followed by
      periodic reactivation to facilitate transmission. This is a highly evolved and
      efficient survival mechanism, which despite being the subject of intense
      research, has proven remarkably difficult to dissect at a molecular level. This
      review will focus on data, emerging from both in vitro and in vivo model systems,
      which provide a framework for a mechanistic understanding of latency and the
      existence and possible significance of non-uniform latent states.

PMID- 15951044
TI  - Enhancement of carboplatin toxicity by Pluronic block copolymers.
AB  - The objective of this study was to examine the effects of three Pluronic triblock
      copolymers (F127, P85, or L61) on the cytotoxicity of carboplatin to the
      DHB/K12/TRb rat colorectal carcinoma cell line. Studies to determine the
      dependence of the sensitization effect on Pluronic dose were carried out for
      polymer concentrations ranging from 0.0001-10% (w/w). To establish the
      carboplatin toxicity and its potential enhancement by Pluronic, the drug was
      delivered to cells in doses ranging from 0-0.5% (w/w) in the presence of Pluronic
      at a constant concentration. These treatment groups were compared to control
      groups receiving carboplatin alone. Cell cytotoxicity resulting from the
      treatments was determined with a mitochondrial enzyme activity assay (WST-1),
      while cell morphology was examined with May-Grunwald and Giemsa staining. Results
      indicate that the greatest enhancement of carboplatin toxicity was induced by
      P85, where the inhibitory concentration (IC(50)) was reduced by 50% (from 0.096
      mg/mL for carboplatin alone to 0.048 mg/mL in presence of P85). L61 was toxic to
      the cells with or without drug (viability<3.5%), while F127 exhibited no
      sensitizing effect and in some cases increased the cell viability to 130% over
      the untreated control. The WST-1 results were confirmed by trypan blue exclusion
      cell counts at 0 and 24 h post treatment. Data conclusively demonstrate that
      Pluronic P85 is the optimal agent for increased cytotoxicity of carboplatin in
      this cell line and can potentially be used not only as a drug delivery scheme but
      also as a chemosensitizing agent in future cancer therapy.

PMID- 15951045
TI  - Cellular fate of oligonucleotides when delivered by nanocapsules of
      poly(isobutylcyanoacrylate).
AB  - Dual-labeled phosphorothioate oligonucleotides were encapsulated in the internal
      aqueous core of poly(isobutylcyanoacrylate) nanocapsules with high yields.
      Intracellular distribution of naked and encapsulated oligomers was assessed on
      cultured vascular smooth muscle cells using cell fractionation and confocal
      microscopy methods. The results showed that cell uptake and more interestingly,
      nuclear accumulation of oligonucleotides were importantly enhanced when the
      oligonucleotides were associated to the nanocapsules as compared to the naked
      oligomers. These results suggested an efficient capacity of this polymeric
      carrier to deliver its payload to the cytosol and nucleus of smooth muscle cells.

PMID- 15951046
TI  - Hyperglycemia among persons with hepatitis C: not the classical diabetic
      phenotype.
AB  - Using data from the Third National Health and Nutrition Examination Survey
      (United States, 1988-1994), we compared clinical phenotypes of hepatitis C virus
      (HCV)-seropositive and seronegative adults aged 20-89 years with hyperglycemia
      (impaired fasting glucose (IFG) or type 2 diabetes, n=3566 including 86 with
      HCV). Seroprevalence was higher among younger persons (3.4% for ages 20-59 versus
      0.9% for ages 60-89, p=0.002), while traditional correlates of diabetes
      (hypertension, coronary heart disease) were more prevalent among older persons
      (both comparisons, p<0.0001). To prevent confounding by age, younger and older
      persons were analyzed separately. In both age groups, HCV was associated with
      signs of hepatic impairment and B-cell clonal expansion (higher alanine
      aminotransferase (ALT) and serum globulin, lower total cholesterol and platelet
      count). Only among younger persons, however, was HCV also associated with a
      marker for advanced hepatic fibrosis (elevated serum ferritin) and absence of the
      classical diabetic phenotype (overweight, coronary heart disease). In addition,
      among younger persons, HCV was currently associated with family history of
      diabetes, positively in persons with diabetes and inversely in those with IFG,
      suggesting that family history of diabetes may serve as a cofactor for
      progression from HCV-associated IFG to diabetes.

PMID- 15951047
TI  - An autoradiographic study of [(18)F]FDG uptake to islets of Langerhans in NOD
      mouse.
AB  - To evaluate the potential of in vivo imaging of accumulation of lymphocytes to
      islets of Langerhans (insulitis), we compared 2-[(18)F]fluoro-2-deoxy-d-glucose
      ([(18)F]FDG) uptake in the pancreas and pancreatic islets of healthy BALB/c mice,
      phenotypically healthy NOD mice with insulitis and diabetic NOD mice. [(18)F]FDG
      was injected i.v. to 14 female BALB/c mice (age 13+/-3 weeks, plasma glucose 8+/
      2 mmol/l) and 21 age-matched female NOD mice (plasma glucose 8+/-4 mmol/l,
      p=0.06). The mice were killed 90-min post injection and distribution of
      radioactivity was analysed using digital autoradiography. There was no
      correlation of plasma glucose concentration with the [(18)F]FDG uptake values.
      Uptake of radioactivity in NOD mice to the islets affected by insulitis was up to
      2.3 times higher (p=0.001) than that to unaffected islets in the same pancreas.
      Uptake to NOD islets with insulitis was also clearly enhanced (1.0-2.3 times
      higher) compared to the islets in the BALB/c mice. In conclusion, NOD mouse
      islets with insulitis accumulate [(18)F]FDG markedly more than islets without
      insulitis or BALB/c islets. However, the relatively small difference in the
      [(18)F]FDG intensity between healthy and diseased islets, combined with the
      limited resolution ability of the positron emission tomography (PET), probably
      prevent the use of [(18)F]FDG in PET studies aiming at in vivo documentation of
      onset and progression of insulitis and prediabetes in mouse and man.

PMID- 15951048
TI  - The cost of epidemiological transition: a study of a decrease in pertussis
      vaccination coverage.
AB  - Based on a transfer function intervention model applied to epidemiological data
      of pertussis incidence and pertussis vaccination in England and Wales, the
      consequences of pertussis vaccination strategies were estimated in terms of
      health effects and economic direct costs. It was established that sixth dose
      pertussis vaccination programs at 90% coverage were the most cost saving for
      short-term and for long-term vaccination prevention strategies. We considered two
      alternative strategies with whole-cell or acellular vaccines for primary course
      and acellular vaccine for two booster doses in children and one booster in
      adolescents. As a rule, programs based on exclusive use of acellular vaccines for
      all the doses were more expensive. Direct costs of programs with the vaccination
      rate at 90% remained systematically lower than the expected cost of pertussis
      disease in the case of non prevention. The stability over time of the vaccination
      coverage at a constant level of 90% made it possible to ensure the largest cost
      saving strategy during the period of 14 years of analysis. Transitions to
      programs with a lower proportion of vaccinated children systematically incurred
      an incremental direct cost for society. The amount of that cost rose with the
      size of the drop in the new vaccination coverage and diminished, due to the J
      curve optimistic effect, when the fall in vaccination rate generated a delayed
      increase in notification cases of pertussis.

PMID- 15951049
TI  - Shaping time: chromatin structure and the DNA replication programme.
AB  - DNA is replicated according to a precise and reproducible temporal pattern. The S
      phase programme has previously been analyzed in metazoan and yeast cells using
      different methods: cytological chromosome banding in human cells and DNA isotopic
      labeling techniques in yeast. Microarray-based approaches for the analysis of the
      replication programme and chromatin structure are bringing us closer to a
      molecular understanding of the factors that determine replication time. In this
      article, I assess the impact of recent investigations and compare our knowledge
      of DNA replication-timing controls in yeast with those of metazoans.

PMID- 15951050
TI  - Functional divergence of proteins through frameshift mutations.
AB  - Frameshift mutations are generally considered to be deleterious and of little
      importance for the evolution of novel gene functions. However, by screening an
      exhaustive set of vertebrate gene families, we found that, when a second
      transcript encoding the original gene product compensates for this mutation,
      frameshift mutations can be retained for millions of years and enable new gene
      functions to be acquired.

PMID- 15951051
TI  - Perioperative anemia and blood transfusions as prognostic factors in patients
      undergoing resection for non-small cell lung cancers.
AB  - We hypothesised that anemia could represent an important prognostic factor and
      perioperative blood transfusions do not reduce the risk of relapse. In order to
      explore this topic, we assessed the correlation of preoperative anemia and blood
      transfusions with survival in patients with resected non-small cell lung cancer
      (NSCLC). Patients who underwent radical surgery for NSCLC at the Department of
      Thoracic Surgery of Universita Politecnica delle Marche from January 1996 through
      December 2001, were included in our study. Four hundred and thirty-nine patients
      were eligible for our analysis. Survival appeared worse in patients with
      haemoglobin (Hb) < or =10 g/dl versus Hb >10 g/dl (p=0.012). Stratifying patients
      in three groups on their Hb level (group 1: Hb < or =10 g/dl; group 2: Hb=10-12
      g/dl; group 3: Hb > or =12 g/dl), we observed a worse prognosis in patients with
      lower Hb levels, too (p=0.0325) and also in the transfused population (p=0.046).
      At multivariate analysis, only the age of patients, pathological stage and Hb
      levels resulted indicators of prognosis. Our results suggested that anemia could
      represent an important prognostic factor in resected NSCLC and correction of
      anemia in the perioperative setting does not reduce the risk of relapse.

PMID- 15951052
TI  - Aberrant methylation of FBN2 in human non-small cell lung cancer.
AB  - FBN2, a large modular extracellular matrix glycoprotein, is known to be a key
      component of human elastic fiber. A loss of FBN2 expression due to promoter
      methylation was recently identified in pancreatic cancer. We examined FBN2
      expression by reverse transcription PCR and aberrant methylation of FBN2 by
      methylation specific PCR in lung cancer cell lines. Aberrant methylation of FBN2
      was present in 55% (6 of 11) of non-small cell lung cancer (NSCLC) cell lines,
      but it absent in small cell lung cancer cell lines. The concordance between loss
      of expression and aberrant methylation of FBN2 was 88% (14 of 16) in the cell
      lines. FBN2 expression was restored after treatment with the demethylating agent,
      5-aza-2'-deoxycytidine in all six cell lines tested that lacked FBN2 expression.
      Among primary NSCLC, 49% (62/126) of cases had FBN2 methylation, but only 7%
      (5/69) of the corresponding nonmalignant lung tissues had it. Although FBN2
      methylation was detected even in patients with early stage disease, it occurred
      frequently in large tumors (p=0.022), with nodal metastasis (p=0.037), or with
      advanced stages of NSCLC (p=0.014). Methylation and silencing of FBN2 in tumor
      cells may play an important role in carcinogenesis, invasion, and metastasis of
      NSCLC.

PMID- 15951053
TI  - Limited efficacy of imatinib mesylate in malignant mesothelioma: a phase II
      trial.
AB  - Twenty-five patients with histologically proven malignant mesothelioma
      participated in a trial of imatinib mesylate (Glivec) with a starting dose of 400
      mg per day taken orally, up to a maximal dose of 800 mg. No responses were
      observed in the patient group, while three patients showed prolonged (>6 months)
      stabilization of disease. The median survival time was 398 days (range 88-840);
      the median time to progression was 63 days (range 29-275). Side effects of the
      medication were mild and included edema, nausea, constipation and diarrhea. We
      conclude that further investigation with monotherapy imatinib in mesothelioma is
      not warranted.

PMID- 15951054
TI  - Influence of the number of repellent-treated and untreated food or water
      containers on intake by the European starling.
AB  - The availability of multiple sources of food and drink has a profound influence
      on choice behavior in rodents. It is not known how other taxa might respond to
      the same kind of variation in availability. We tested European starlings (Sturnus
      vulgaris) with various combinations of unadulterated and repellent-treated
      (0.025% citronellyl acetate) resources. In Experiment 1, birds drank more plain
      than repellent-treated water than when given (a) 2 bottles of plain water and 2
      of repellent-water, or (b) 3 bottles of plain water and 1 of repellent-water.
      However, they drank more repellent than water when given 3 bottles of repellent
      water and 1 of plain water. Thus, the aversion to the repellent became
      indifference when repellent-water was abundant. In Experiment 2, birds ate more
      untreated than treated food when given (a) 1 cup of untreated food and 1 cup of
      treated food or (b) 2 cups of untreated food and 1 of treated food. They ate
      equal amounts of untreated and treated food when given 1 cup of untreated food
      and 2 cups of treated food. These results demonstrate the effect of relative
      availability on choice, and imply that availability should be considered when
      using repellents.

PMID- 15951055
TI  - Effects of dietary and pharmacological manipulations on appetitive and
      consummatory aspects of feeding in non-human primates.
AB  - This study examined how pharmacological and behavioral manipulations affect
      appetitive and consummatory aspects of feeding of baboons. Baboons have access to
      food 24 h each day, but they must complete a two-phase operant procedure in order
      to eat. Responding on one lever during a 30-min appetitive phase was required
      before animals could start a consumption phase, i.e. a meal, where responding on
      another lever led to food delivery. Responding during the appetitive phase
      resulted in presentations of food-related stimuli only. Decreasing session
      length, increased appetitive behavior and increased meal size. Limiting the
      number of meals to a single 90 min meal each day but increasing the number of
      food pellets the animals received increased the size of meal, but did not
      increase appetitive behavior. These findings suggest that time since the previous
      meal has a greater effect on appetitive behavior than the size of the previous
      meal. Amphetamine (AMPH), which increases dopamine, decreased food intake at
      doses that did not affect appetitive behavior, indicating that appetitive and
      consummatory aspects of eating can be pharmacologically differentiated.
      Increasing how frequently animals could earn food-related stimuli in the
      appetitive phase and food in the consummatory phase increased both appetitive and
      consumatory behavior. Under these conditions, AMPH nearly doubled appetitive
      behavior at doses that decreased food intake by nearly 50 percent. When animals
      had one meal, of self-determined duration, meal size increased without affecting
      appetitive behavior, further demonstrating that appetitive behavior can be
      independent of the size of the previous meal and not predictive of the size of
      the subsequent meal. Under these conditions, AMPH decreased food intake at doses
      that did not affect appetitive behavior. In contrast, dexfenfluramine (DFEN),
      which increases serotonin, decreased both appetitive and consumatory behavior.
      Thus, it is possible to independently manipulate the appetitive and consummatory
      aspects of eating using both pharmacological and behavioral interventions
      indicating that it may be possible to develop medications that selectively affect
      appetitive or consummatory aspects of eating.

PMID- 15951056
TI  - Exercise energy expenditure is not consciously detected due to oro-gastric, not
      metabolic, basis of hunger sensation.
AB  - We tested the hypothesis that exercise energy expenditure (EEE) will elicit
      reflex metabolic compensations but no increases in hunger. Exercise expended 800
      kcal once when fasted and at another time in a post-prandial state. During
      fasting exercise, pre-meal ratings of hunger were unaffected by EEE, but plasma
      concentrations of ghrelin, growth hormone and free fatty acids were higher than
      in the absence of EEE. We propose that the perception of hunger is based on the
      vagal, lateral hypothalamic and cortical projections of oral and gastro
      intestinal (GI) stimuli and that EEE triggers neuroendocrine compensations and
      influences hunger indirectly by affecting GI functions.

PMID- 15951058
TI  - Better late than never: a re-examination of ethical dilemmas in coping with
      severe acute respiratory syndrome.
AB  - At the end of 2002 severe acute respiratory syndrome (SARS) emerged and spread
      worldwide. The pathogen was unknown, as was its mechanism of transfer, and there
      was no effective therapy for the disease. There was a large element of hysteria
      and anxiety in society's reaction to SARS. The initial steps taken to cope with
      SARS were clear-cut and even dramatic. Decision-making in a time of emergency is
      associated with a high potential for ethical dilemmas and conflicts. In the
      course of efforts to cope with a threatening disease, it is important to appraise
      our activities from an ethical point of view. A retrospective look at this period
      of time shows that we did not do this. This article examines the ethical aspects
      of the process undertaken to cope with SARS in our medical centre.

PMID- 15951057
TI  - Outbreak of methicillin-resistant Staphylococcus aureus in two nursing homes in
      Central Norway.
AB  - Until recently, infections with methicillin-resistant Staphylococcus aureus
      (MRSA) have mainly been associated with hospital outbreaks in Norway. However,
      increasingly cases are contracted outside hospitals. This paper reports the first
      two outbreaks of MRSA in two nursing homes in central Norway, affecting 23
      residents and five staff members. Pulsed-field gel electrophoresis analysis
      showed that all strains from nursing home A were identical and that the strains
      from nursing home B were genotypically similar with one or two band differences.
      Multi-locus sequence typing (MLST) showed that the strains from the two nursing
      homes belong to clonal complex 45, with each strain being a single-locus variant
      of sequence type 45 (ST 45), a well-known European epidemic strain. No evident
      source of the two outbreaks was found, and there was no obvious connection
      between the two outbreaks. The latter is also supported by the minor differences
      observed by MLST, suggesting a connection at some time in the past. The outbreaks
      led to a heavier workload and economic strain on both nursing homes. The outbreak
      in nursing home A was brought to an end, whereas two residents remained colonized
      in nursing home B despite several eradication attempts. These outbreaks show the
      potential for MRSA spread in a nursing home. If the prevalence of MRSA in Norway
      continues to increase, nursing home staff and residents may have to be included
      in the groups to be screened for MRSA upon hospital admission.

PMID- 15951059
TI  - Age-related changes of hypocretin in basal forebrain of guinea pig.
AB  - Hypocretin-1 (hcrt-1) and hypocretin-2 (hcrt-2) have been implicated in a wide
      variety of functions including sleep and wakefulness as well as related
      behaviors. Many of these functions of the hypocretins involve the activation of
      cholinergic neurons in the basal forebrain (BF). These neurons have been shown to
      exhibit age-related changes in a variety of species. In the present experiment,
      in adult and aged guinea pigs, we compared hypocretin immunoreactivity in regions
      of the BF that include the medial septal nucleus (MS), the vertical and
      horizontal limbs of the diagonal band of Broca (VDB and HDB) and the magocellular
      preoptic nucleus (MCPO). In adult guinea pigs (3-5 months of age), all of the
      preceding BF regions contained dense hypocretin fibers with varicosities. On the
      contrary, in old guinea pigs (27-28 months), although the MS exhibited a similar
      intensity of hypocretin immunoreactivity compared with the adult guinea pig,
      there was a significant decrease in the intensity of immunoreactivity of
      hypocretinergic fibers in the VDB, HDB and MCPO. These data indicate that the
      hypocretinergic innervation of specific nuclei of the BF is compromised during
      the aging process. We suggest that the reduction in hypocretinergic innervation
      of the BF nuclei may contribute to the age-related changes in the states of sleep
      and wakefulness as well as deficits in related systems that occur in old age.

PMID- 15951061
TI  - Synthesis of 2,5- and 3,5-diphenylpyridine derivatives for DNA recognition and
      cytotoxicity.
AB  - A series of 2,5- and 3,5-diphenylpyridine derivatives was synthetised in high
      yields. A versatile chemical strategy allows the design of diphenylpyridines
      differently substituted with cationic or neutral side chains. The interaction of
      the molecules with DNA was investigated by biophysical and biochemical methods
      and an AT-binder (20) was characterised. A few cytotoxic molecules were
      identified but their antiproliferative activity does not correlate with DNA
      binding. Two compounds 18 and 22 showed significant antiproliferative activity
      and provide a novel route to potential anticancer agents.

PMID- 15951060
TI  - Auto-inhibitory control of peptidergic molluscan neurons and reproductive
      senescence.
AB  - We recently, characterized a novel peptide of the egg-laying controlling
      caudodorsal cells (CDC) of Lymnaea stagnalis. Here, we show that the novel
      peptide has autoinhibitory actions and its expression is significantly up
      regulated in reproductively senescent animals. Intracellular recordings show that
      when bath-applied to the central nervous system in vitro, the peptide reduces the
      depolarizing after potential (DAP) in CDCs without affecting the action potential
      threshold and -amplitude and the resting membrane potential. Moreover, peptide
      application can terminate an ongoing after discharge in the CDCs or, when
      electrical stimulation fails to induce an after discharge, can terminate the long
      lasting depolarization. Semiquantitative peptide profiling by mass spectrometry
      demonstrated correct processing and targeting of peptides in the CDC somata and
      axon terminals of reproductively senescent animals. Interestingly, the level of
      the autoinhibitory peptide was selectively increased in the CDCs of
      reproductively senescent animals. Our results indicate that a shift in balance
      between excitatory and inhibitory auto-transmitter peptides in the CDC system of
      old non-egg-laying animals, plays a role in after discharge failure in CDCs of
      reproductively senescent Lymnaea.

PMID- 15951062
TI  - Regioselective synthesis and estrogenicity of (+/-)-8-alkyl-5,7-dihydroxy-4-(4
      hydroxyphenyl)-3,4-dihydrocoumarins.
AB  - Nine new (+/-)-8-alkyl-5,7-dihydroxy-4-(4-hydroxyphenyl)-3,4-dihydrocoumarins
      have been synthesized from 2,4,6-trimethoxybenzaldehyde via a short, efficient,
      and regioselective pathway, together with the unsubstituted analogue (+/-)-5,7
      dihydroxy-4-(4-hydroxyphenyl)-3,4-dihydrocoumarin. The compounds were tested for
      estrogenic activity using a yeast-based estrogen screen. Weak estrogenicity was
      determined for seven members of the series.

PMID- 15951063
TI  - Unified drug-target interaction thermodynamic Markov model using stochastic
      entropies to predict multiple drugs side effects.
AB  - Most of present molecular descriptors consider just the molecular structure. In
      the present article we pretend extending the use of Markov chain (MC) models to
      define novel molecular descriptors, which consider in addition other parameters
      like target site or toxic effect. Specifically, this molecular descriptor takes
      into consideration not only the molecular structure but the specific system the
      drug affects too. Herein, it is developed a general Markov model that describes
      21 different drugs side effects grouped in 10 affected biological systems for 193
      drugs, being 311 cases finally. The data were processed by linear discriminant
      analysis (LDA) classifying drugs according to their specific side effects,
      forward stepwise was fixed as strategy for variables selection. The average
      percentage of good classification and number of compounds used in the
      training/predicting sets were 92.6/91.7% for cardiovascular manifestation (25 out
      of 27)/(18 out of 20); 89.3/83.9% for dermal manifestations (25 out of 18)/(18
      out of 21); 88.9/88.9% for endocrine manifestations (16 out of 18)/(12 out of
      14); 88.9/88.2% for psychiatric manifestations (32 out of 36)/(24 out of 27);
      88.5/85.6% for systemic phenomena (23 out of 26)/(17 out of 20); 85.7/91.7% for
      gastrointestinal manifestations (36 out of 42)/(29 out of 32); 83.3/79.2% for
      metabolic manifestations (15 out of 18)/(11 out of 14); 81.8/78.0% for
      neurological manifestations (27 out of 33)/(20 out of 25); 75.0/74.0% for
      hematological manifestations (36 out of 48)/(27 out of 36) and 74.3/72.8% for
      breathing manifestations (26 out of 35)/(19 out of 26). Finally, application of
      back-projection analysis (BPA) provides physic interpretation in structural terms
      through molecular graphics of the toxic effects predicted with these QSTR models.
      This article develops a mathematical model that encompasses a large number of
      drugs side effects grouped in specifics systems using stochastic entropies of
      interaction (Thetak (j)) by the first time.

PMID- 15951064
TI  - [Alzheimer's disease: cardiovascular risk factors must be assessed].
AB  - BACKGROUND: Dementia is nowadays of major importance in public health.
      Alzheimer's disease and vascular cognitive impairments are its main aetiology in
      the elderly. The cause of Alzheimer's disease remains unknown. The factor
      initiating the physiopathology of this neurodegenerative disease is source of
      controversy. CURRENT KNOWLEDGE AND KEY POINTS: The theory of a neurotoxicity
      initiated by amyloid deposition is questioned. A growing number of data suggest a
      central role of cardiovascular risk factors and alteration of arterial walls,
      inducing chronic brain hypoperfusion, as the primary trigger in the
      physiopathology of the disease. These data are based on epidemiological,
      physiopathological, neuroimaging, neuropathological and pharmacological studies.
      However, the exact link between arteriosclerosis, vascular cognitive impairment
      and Alzheimer's disease remains controversial. FUTURE PROSPECTS AND PROJECTS:
      These debates point out the crucial importance of the assessment of
      cardiovascular risk factors, as a preventable cause, either of cognitive decline,
      morbidity and mortality. In this aim, major targets could be different when
      primary or secondary prevention are at stake. These controversies also suggest
      new research directions towards Alzheimer's disease physiopathology, and for
      pharmacological interventions aimed on the prevention of cognitive decline or the
      curative treatment for this disease.

PMID- 15951065
TI  - [Cobalamin deficiencies in adults: update of etiologies, clinical manifestations
      and treatment].
AB  - PURPOSE: Update of the adult cobalamin deficiencies. CURRENT KNOWLEDGE AND KEY
      POINTS: More precise definitions establish the true cobalamin deficiencies and
      determine their real epidemiology. The current clinical data suggest the concept
      of food-cobalamin malabsorption as the leading etiology of cobalamin deficiency.
      The new features of cobalamin deficiency include neurological, gynecological and
      vascular manifestations. Current treatment modalities include nasal, sublingual
      and oral cobalamin administration. PROSPECTS AND PROJECTS: Studies are in the way
      to establish the relevance of the new clinical manifestations and to validate the
      usefulness of oral cobalamin therapy.

PMID- 15951066
TI  - Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse
      genetics are attenuated and efficacious in African green monkeys.
AB  - A set of recombinant, live attenuated human parainfluenza virus type 1 (rHPIV1)
      vaccine candidates was evaluated for attenuation, immunogenicity, and protective
      efficacy in African green monkeys (AGMs). Temperature sensitive (ts) and non-ts
      attenuating (att) mutations in the P/C and L genes were introduced individually
      or in various combinations into rHPIV1, including the C(R84G) and HN(T553A)
      mutations identified in the present work and the C(F170S), L(Y942A), and L(L992C)
      mutations identified previously. The rHPIV1 vaccine candidates exhibited a
      spectrum of attenuation in AGMs. One genetically and phenotypically stable
      vaccine candidate, rC(R84G/F170S)L(Y942A/L992C), was attenuated and efficacious
      in AGMs and is a promising live attenuated intranasal HPIV1 vaccine candidate
      suitable for clinical evaluation.

PMID- 15951067
TI  - Vaccine and adjuvant activity of recombinant subunit B of E. coli enterotoxin
      produced in yeast.
AB  - Escherichia coli heat-labile enterotoxin (LT) and cholera toxin (CT) have been
      studied intensively as vaccines against diseases caused by those bacteria and as
      adjuvants for mucosal vaccination. Two major problems interfere with the use of
      these promising adjuvants: their toxicity and the residual bacterial endotoxins
      mixed with the desired LT. In this study, subunit B of LT was expressed in Pichia
      pastoris yeast cells (yrLTB) and the recombinant protein was purified and
      concentrated by ion-exchange chromatography. The final yield of the recombinant
      protein was 5-8 mg/l induction medium. The molecule is in pentameric form and
      binds to GM1 gangliosides. When given orally to chickens, anti-LTB antibodies
      were produced, exhibiting its ability to cross the digestive system and induce an
      immune response. The adjuvant activity of yrLTB was proven by fusing it to viral
      protein 2 (VP2) of infectious bursal disease virus. Birds intramuscularly
      vaccinated with this molecule exhibit 70-100% protection, in a dose-response
      dependent manner. This method eliminated the bacterial endotoxins and enabled the
      production of large quantities of LTB. Expression in a eukaryotic system allows
      the production of fusion proteins that require post-translational modifications.
      This may allow oral vaccination with a protein fused to yrLTB. The approach
      described in this study will enable the efficient production of a non-toxic,
      eukaryotically expressed enterotoxin as a vaccine against the toxin itself or as
      a carrier or adjuvant for foreign vaccine molecules.

PMID- 15951068
TI  - Relative efficacy of inactivated bovine herpesvirus-1 (BHV-1) vaccines.
AB  - The relative efficacy of four commercially available inactivated bovine
      herpesvirus-1 (BHV-1) vaccines was directly assessed in controlled studies in 5-6
      month-old, BHV-1 naive calves. The sero-response due to the basic course of two
      intramuscular vaccinations was closely similar for three of four vaccines whereas
      one vaccine did not induce seroconversion in five of six calves. At the level of
      challenge virus shedding in nasal mucus, all four vaccines were significantly
      protective but to a markedly variable degree. Clinically, however, the relative
      protection ranking of the vaccines was different to that observed for challenge
      virus shedding. There was no obvious correlation observed between pre-challenge
      circulating virus neutralising antibody titre and vaccine-induced protection
      against virus shedding or clinical signs following the intranasal BHV-1
      challenge. Present comparative findings suggest that commercially available BHV-1
      vaccines are likely to be of variable potency in the natural host.

PMID- 15951069
TI  - Natural radioactivity and dose assessment for phosphate rocks from Wadi El
      Mashash and El-Mahamid Mines, Egypt.
AB  - The activity concentrations of (226)Ra, (232)Th and (40)K have been measured by
      gamma spectroscopy (sodium iodide NaI(Tl) detector) in phosphate rock samples,
      collected from the Wadi El-Mashash, a site located in the central eastern desert,
      and El-Mahamid in the Nile valley, Egypt. The average activity concentrations of
      (226)Ra, (232)Th and (40)K (Bq kg(-1)) in phosphate rocks were 665.8+/-33.4,
      329.4+/-17 and 587.6+/-29.4 for Wadi El-Mashash and 566.8+/-28.6, 217.3+/-11.8
      and 560.1+/-28 for El-Mahamid, respectively. The corresponding values for shale
      rocks were 85.2+/-5.7, 93.3+/-5.6 and 303.1+/-15.2 Bq kg(-1), respectively. As a
      measure of radiation hazard to the occupational workers and public, the Ra
      equivalent activities, representative level index and dose rates due to natural
      radionuclides at 1 m above the ground surface were estimated. The calculated
      external gamma-radiation dose received by the workers of the phosphate mine are
      538 and 418 microSv/y, which is far below the permitted dose of 20 mSv/y
      recommended by the International Commission of Radiation Protection [ICRP-60,
      1990. Radiation Protection: 1990 Recommendation of the International Commission
      on Radiological Protection, Oxford, Pergamon Preis.] for workers.

PMID- 15951070
TI  - Natural radioactivity in farm soil and phosphate fertilizer and its environmental
      implications in Qena governorate, Upper Egypt.
AB  - Samples of phosphate fertilizers and farm soils, taken to a depth of up to 30 cm
      in cultivated land, were collected over the Qena governorate, Upper Egypt.
      Activity concentration of background radionuclides such as (226)Ra, (232)Th and
      (40)K of these samples were determined by gamma-ray spectrometry. The results
      show that these radionuclides were present in concentrations of 366+/-10.5,
      66.7+/-7.3 and 4+/-2.6 Bq/kg for phosphate fertilizers. For farm soil and Nile
      island's soil the corresponding values were 13.7+/-7, 12.3+/-4.6, 1233+/-646 and
      11.9+/-6.7, 10.5+/-6.1, 1636+/-417 Bq/kg, respectively. The radium equivalent
      activity (Ra(eq)), the representative level index, I(gamma r), and absorbed dose
      in air for all samples were calculated. The data were discussed and compared with
      those given in the literature.

PMID- 15951071
TI  - Variation in stakeholder opinion on countermeasures across Europe.
AB  - A compendium of agricultural countermeasures and rural waste disposal options has
      been compiled as part of the EC STRATEGY (Sustainable Restoration and Long-Term
      Management of Contaminated Rural, Urban and Industrial Ecosystems) project. The
      compendium was discussed by the FARMING (Food and Agriculture Restoration
      Management Involving Networked Groups) network of stakeholders during meetings of
      national panels in the UK, Finland, Belgium, Greece and France in 2002. Their
      preliminary feedback has been summarised in terms of whether an option is
      generally acceptable, unacceptable or only acceptable under specific
      circumstances. A considerable divergence of opinion between national panels was
      apparent for many of the options considered. This could be attributed to
      differences in geomorphology, climate, land management, infrastructure, consumer
      confidence, sociopolitical context and culture. Where consensus was reached
      between stakeholders it was generally for those countermeasures that provide
      public reassurance, sustain farming practices and minimise environmental impact.
      Furthermore, whilst there was general agreement that contaminated food should not
      enter the food chain, many of the options proposed for its subsequent management
      were not generally acceptable to stakeholders.

PMID- 15951072
TI  - Achievements, difficulties and future challenges for the FARMING network.
AB  - The EC FARMING network (Food and Agriculture Restoration Management Involving
      Networked Groups) was set up to bring together the many and diverse stakeholders
      who would be involved in intervention following wide scale radioactive
      contamination of the food chain, so that acceptable strategies can be developed
      for maintaining agricultural production and safe food supply. The network
      comprises stakeholder panels in the UK, Finland, Belgium, France and Greece that
      have met regularly since 2001 to debate, discuss and exchange opinion on the
      acceptability, constraints and impact of various countermeasure options and
      strategies. The objectives of this paper are to consolidate the main achievements
      of the FARMING project over the period 2000-2004, to highlight the various
      difficulties that were encountered and to discuss the challenges for engaging
      stakeholders in off-site emergency management and long-term rehabilitation in the
      future.

PMID- 15951073
TI  - Feasibility of an endoscopic approach to the submandibular neck region-
      experimental and clinical results.
AB  - We have investigated the feasibility of an exclusively endoscopic approach to the
      submandibular region in four pigs, four cadavers and two women. We inflated the
      subplatysmal space with carbon dioxide at low pressure. The submandibular gland
      and the jugulodigastric region were easy to identify once the correct anatomical
      space had been dissected and inflated. Four endoscopic resections of the
      submandibular gland were done successfully.

PMID- 15951074
TI  - Osteoarticular allograft reconstruction of the distal radius after bone tumour
      resection.
AB  - Resection of the distal end of the radius is indicated in the treatment of
      locally aggressive primary benign and malignant bone tumours. The aim of this
      study was to evaluate the technique of osteoarticular allograft reconstruction of
      this bone defect. We analysed 12 patients retrospectively with a minimum follow
      up of 2 years (range 26-145 months, median 52 months). Three patients had a
      malignant tumour and nine had a giant cell tumour. The patients ages ranged from
      13 to 65 years. The mean resected length of the radius was 6.6 (range 4-14)cm.
      Non-union of the osteotomy line was diagnosed 6 months after surgery in one case
      and needed bone grafting. Distal radio-ulnar joint instability was observed in
      eight cases. Subchondral bone alterations and joint narrowing were present in all
      cases but were painful in only one patient. The mean range of motion was 51
      degrees of flexion and 37 degrees of extension.

PMID- 15951075
TI  - Hand elevation test for assessment of carpal tunnel syndrome.
AB  - The Hand Elevation test is a new provocative test for the diagnosis of carpal
      tunnel syndrome. We have investigated the sensitivity and specificity of this
      test in 48 patients with a clinical diagnosis of carpal tunnel syndrome and
      compared it to Tinel's and Phalen's tests. The Hand Elevation test was found to
      be 88% sensitive and 98% specific. This test is a simple, reproducible
      provocative test which is easily employed in conjunction with other known tests
      to assist in the diagnosis of carpal tunnel syndrome.

PMID- 15951076
TI  - Adsorption of arsenate on soils. Part 1: laboratory batch experiments using 16
      Chinese soils with different physiochemical properties.
AB  - Laboratory batch experiments were carried out to study the adsorption of arsenate
      on 16 Chinese soils with different physicochemical properties. Wide differences
      in arsenate adsorption were observed, and the Jiangxi and Hubei soils were more
      effective sorbents for arsenate than other soils. The Langmuir one-surface and
      two-surface equations were used to model the arsenate adsorption data. Except for
      the Jiangxi and Hubei soils, the Langmuir one-surface equation gave reasonably
      good fits to the arsenate adsorption data. However, the Langmuir two-surface
      equation generally provided a better fit than the Langmuir one-surface equation.
      For soils with relative high organic matter (OM), dissolved organic carbon (DOC)
      or extractable phosphate, the Langmuir one-surface and two-surface equations
      described the adsorption isotherms similarly. In contrast, for soils with
      relatively low contents of OM, DOC or extractable phosphate, the Langmuir two
      surface equation gave the better fit to the arsenate adsorption data.

PMID- 15951077
TI  - Evidence of immunomodulation in nestling American kestrels (Falco sparverius)
      exposed to environmentally relevant PBDEs.
AB  - We investigated whether exposure to environmentally relevant polybrominated
      diphenyl ethers (PBDEs) causes immunomodulation in captive nestling American
      kestrels (Falco sparverius). Eggs within each clutch, divided by laying sequence,
      were injected with safflower oil or penta-BDE congeners-47, -99, -100, and -153
      dissolved in safflower oil (18.7 microg sigmaPBDEs/egg) approximating Great Lakes
      birds. For 29 days, nestlings consumed the same PBDE mixture (15.6+/-0.3 ng/g
      body weight per day), reaching sigmaPBDE body burden concentrations that were
      120x higher in the treatment birds (86.1+/-29.1 ng/g ww) than controls (0.73+/
      0.5 ng/g ww). PBDE-exposed birds had a greater PHA response (T-cell-mediated
      immunity), which was negatively associated with increasing BDE-47 concentrations,
      but a reduced antibody-mediated response that was positively associated with
      increasing BDE-183 concentrations. There were also structural changes in the
      spleen (fewer germinal centers), bursa (reduced apoptosis) and thymus (increased
      macrophages), and negative associations between the spleen somatic index and
      sigmaPBDEs, and the bursa somatic index and BDE-47. Immunomodulation from PBDE
      exposure may be exacerbated in wild birds experiencing greater environmental
      stresses.

PMID- 15951078
TI  - Survival, Pb-uptake and behaviour of three species of earthworm in Pb treated
      soils determined using an OECD-style toxicity test and a soil avoidance test.
AB  - Mature (clitellate) Eisenia andrei Bouche (ultra epigeic), Lumbricus rubellus
      Hoffmeister (epigeic), and Aporrectodea caliginosa (Savigny) (endogeic)
      earthworms were placed in soils treated with Pb(NO(3))(2) to have concentrations
      in the range 1,000 to 10,000 mg Pb kg(-1). After 28 days LC50(-95%confidence
      limit)(+95%confidence limit) values were E. andrei 5824(-361)(+898) mg Pb kg(-1),
      L. rubellus 2867(-193)(+145) mg Pb kg(-1) and A. caliginosa2747(-304)(+239) mg Pb
      kg(-1) and EC50s for weight change were E. andrei2841(-68)(+150) mg Pb kg(-1), L.
      rubellus1303(-201)(+240) mg Pb kg(-1) and A. caliginosa1208(-206)(+212) mg Pb kg(
      1). At any given soil Pb concentration, Pb tissue concentrations after 28 days
      were the same for all three earthworm species. In a soil avoidance test there was
      no difference between the behaviour of the different species. The lower
      sensitivity to Pb exhibited by E. andrei is most likely due to physiological
      adaptations associated with the modes of life of the earthworms, and could have
      serious implications for the use of this earthworm as the species of choice in
      standard toxicological testing.

PMID- 15951079
TI  - Dynamics of Cd, Cu and Zn accumulation in organs and sub-cellular fractions in
      field transplanted juvenile yellow perch (Perca flavescens).
AB  - Juvenile yellow perch (Perca flavescens) were caught in a reference lake and
      transplanted to cages held within a lake impacted by mining activities, with
      elevated levels of aqueous bioavailable copper (Cu(2+)), zinc (Zn(2+)) and
      cadmium (Cd(2+)). Fish were sampled from the cages over 70 d and changes in metal
      concentrations were followed over time in the gills, gut, liver and kidney. In
      addition, the hepatic sub-cellular partitioning of the three metals was
      determined by differential centrifugation of liver samples, yielding the
      following fractions: cellular debris; organelles; heat-denaturable proteins
      (HDP); and heat-stable proteins (HSP) (including metallothionein). In
      transplanted fish, Cd concentrations increased in all the organs sampled, whereas
      Cu mainly increased in the gills, gut and liver but not the kidney; some slight
      accumulation of Zn occurred in the kidneys and gills of the transplanted fish.
      The sub-cellular partitioning results demonstrated that metal-handling strategies
      in juvenile yellow perch differed among metals. Cellular sequestration in the HSP
      fraction was an important strategy used by these fish in response to increased
      ambient Cd. Accumulation of Zn was not seen in the organs examined, indicating
      that transplanted perch were able to either reduce influx, or increase efflux
      rates of this metal. The response of yellow perch to elevated ambient Cu appeared
      to combine the strategies used for Cd and Zn, as both cellular sequestration and
      reduced accumulation were observed in transplanted fish.

PMID- 15951080
TI  - Diuron mobility through vineyard soils contaminated with copper.
AB  - The herbicide diuron is frequently applied to vineyard soils in Burgundy, along
      with repeated treatments with Bordeaux mixture (a blend of copper sulfate and
      calcium hydroxide) that result in elevated copper concentrations. Cu could in
      principle affect the fate and transport of diuron or its metabolites in the soil
      either directly by complexation or indirectly by altering the populations or
      activity of microbes involved in their degradation. To assess the effect of high
      Cu concentrations on diuron transport, an experiment was designed with ten
      undisturbed columns of calcareous and acidic soils contaminated with 17--509 mg
      kg(-1) total Cu (field-applied). Grass was planted on three columns. Diuron was
      applied to the soils in early May and in-ground lysimeters were exposed to
      outdoor conditions until November. Less than 1.2% of the diuron applied was found
      in the leachates as diuron or its metabolites. Higher concentrations were found
      in the effluents from the grass-covered columns (0.1--0.45%) than from the bare
      soil columns (0.02--0.14%), and they were correlated with increases in dissolved
      organic carbon. The highest amounts of herbicide were measured in acidic-soil
      column leachates (0.98--1.14%) due to the low clay and organic matter contents of
      these soils. Cu also leached more readily through the acidic soils (32.8--1042
      microg) than in the calcareous soils (9.5--63.4 microg). Unlike in the leachates,
      the amount of diuron remaining in the soils at the end of the experiment was
      weakly related to the Cu concentrations in the soils.

PMID- 15951081
TI  - Heavy metal concentrations in soil and earthworms in a floodplain grassland.
AB  - We determined accumulated heavy metal concentrations (Cd, Pb, Cu, Zn) of
      earthworms in moderately contaminated floodplain soils. Both soil and mature
      earthworms were sampled before and after flooding and earthworm species were
      identified to understand species specific differences in bioconcentration.
      Accumulated metal concentrations in floodplain earthworms differed before and
      after flooding. Differences in uptake and elimination mechanisms, in food choice
      and living habitat of the different earthworm species and changes in speciation
      of the heavy metals are possible causes for this observation. Regression
      equations taken from literature, that relate metal accumulation by earthworms in
      floodplains as a function of metal concentration in soil, performed well when all
      species specific data were combined in an average accumulation, but did not
      address differences in accumulation between earthworm species.

PMID- 15951082
TI  - A biomarker model of sublethal genotoxicity (DNA single-strand breaks and
      adducts) using the sentinel organism Aporrectodea longa in spiked soil.
AB  - There is a need to develop risk biomarkers during the remediation of contaminated
      land. We employed the earthworm, Aporrectodea longa (Ude), to determine whether
      genotoxicity measures could be applied to this organism's intestinal tissues.
      Earthworms were added, for 24h or 7 days, to soil samples spiked with
      benzo[a]pyrene (B[a]P) and/or lindane. After exposure, intestinal tissues
      (crop/gizzard or intestine) were removed prior to the measurement in
      disaggregated cells of DNA single-strand breaks (SSBs) by the alkaline comet
      assay. Damage was quantified by comet tail length (CTL, microm). B[a]P 24-h
      exposure induced dose-related increases (P<0.0001) in SSBs. Earthworm intestine
      was significantly (P<0.0001) more susceptible than crop/gizzard to B[a]P and/or
      lindane. However, both tissues appeared to acquire resistance following 7-day
      exposure. B[a]P-DNA adducts, measured by (32)P-postlabelling, showed a two-adduct
      spot pattern. This preliminary investigation suggests that earthworm tissues may
      be incorporated into genotoxicity assays to facilitate hazard identification
      within terrestrial ecosystems.

PMID- 15951083
TI  - Cognitive-behavioral therapy for primary insomnia.
AB  - Primary insomnia (PI) is a prevalent form of sleep difficulty that impairs
      diurnal functioning, reduces quality of life and enhances health care
      utilization/costs for millions worldwide. Whereas the underlying pathophysiology
      of PI remains poorly understood, it is widely accepted that a host of cognitive
      and behavioral factors play important roles in perpetuating this condition. As
      such, a multi-factorial, cognitive-behavioral therapy (CBT) has emerged as a
      "treatment of choice" for managing the sleep/wake complaints of PI sufferers.
      This article considers the nature and relative merits of CBT for treating PI
      patients. In addition, this article reviews studies supporting the general
      efficacy and clinical effectiveness of CBT for treating PI complaints. Issues
      related to treatment implementation as well as factors that mediate patients'
      responses to CBT and predict treatment acceptance/outcome are also considered.
      Finally, remaining questions regarding CBT's application to PI are considered,
      and suggestions for future research are provided.

PMID- 15951084
TI  - The role of behavioral sleep medicine in the assessment and treatment of sleep
      disordered breathing.
AB  - With the dramatic rise in obesity in the United States, comorbid medical issues,
      such as sleep apnea and other forms of sleep disordered breathing (SDB), are
      becoming increasingly prevalent. Individuals with SDB have impairments in social,
      cognitive, and emotional functioning and an overall reduction in quality of life.
      Continuous positive airway pressure (CPAP) is the first-line treatment for SDB.
      CPAP use is associated with improvements in psychosocial functioning when
      individuals use the machine regularly. Unfortunately, CPAP adherence rates are
      often low. Patients sometimes discontinue CPAP therapy due to undesirable side
      effects, such as anxiety, insomnia, and nasal discomfort, or inconvenience. The
      goal of this review is to highlight the growing role of behavioral sleep medicine
      in the assessment and treatment of SDB and psychosocial impairments comorbid with
      SDB. More than any other health specialty, psychologists with behavioral sleep
      medicine experience are in the best position to treat psychiatric symptoms
      exacerbated by SDB-related sleep disturbances. Behavioral sleep medicine
      specialists also possess the expertise to address psychological obstacles to CPAP
      use. The assimilation of behavioral sleep medicine specialists into sleep clinics
      is likely to improve the overall quality of care for patients with SDB.

PMID- 15951085
TI  - A longitudinal assessment of inter-sectoral participation in a community-based
      diabetes prevention programme.
AB  - To understand the development of inter-sectoral participation in the three
      intervention municipalities of Stockholm Diabetes Prevention Programme (SDPP)
      case studies with a longitudinal assessment were conducted using the spidergram
      method, document analysis and group discussions. At three time points, the
      members of the local steering committees assessed the extent of participation
      from narrow to wide inter-sectoral participation in five key areas: planning,
      resources, leadership, network and implementation. Wide participation of various
      interest groups was recognised in planning and implementing activities whereas
      local resources, the representation of the leadership and the extent of the
      network were perceived as more restricted. Expert involvement varied during the
      programme period but was not regarded as exerting control over the local
      programmes. Participation within the local steering committees decreased, with a
      stronger focus on the project co-ordinator and other local partners in latter
      years. The extent of partner engagement increased due to focusing on activities
      approaching multi-sector collaboration and institutionalisation. Overall,
      communication and shared responsibility appeared critical in influencing both the
      development and perception of participation. In conclusion, to understand the
      dynamic process of participation at different times, areas and levels, the
      development and use of evaluation designs combining different methods and
      information sources throughout the lifespan of a project are recommended.

PMID- 15951086
TI  - Attention deficit hyperactivity disorder and borderline personality disorder.
AB  - To evaluate the association between attention deficit hyperactivity disorder
      (ADHD) and the diagnosis of borderline personality disorder (BPD) in adulthood, a
      systematic review of published follow-up data, mainly from observational studies
      was done. Electronic databases Medline, PsychInfo and PSYNDEXplus were searched
      from their earliest entries. All studies suggested significant relationships
      between ADHD and BPD. From a phenomenological point of view there seem to exist
      some similarities between these two disorders: deficits in affect regulation and
      impulse control, substance abuse, low self esteem and disturbed interpersonal
      relationship are common in both conditions. From a neuropsychological point of
      view dissociation in BPD might be regarded as a special form of behavioral
      inhibition and sustained attention comparable to ADHD. Possible therapeutic
      strategies of comorbid ADHD and BPD are discussed.

PMID- 15951087
TI  - Chronic treatment with sulbutiamine improves memory in an object recognition task
      and reduces some amnesic effects of dizocilpine in a spatial delayed-non-match-to
      sample task.
AB  - The effect of a sulbutiamine chronic treatment on memory was studied in rats with
      a spatial delayed-non-match-to-sample (DNMTS) task in a radial maze and a two
      trial object recognition task. After completion of training in the DNMTS task,
      animals were subjected for 9 weeks to daily injections of either saline or
      sulbutiamine (12.5 or 25 mg/kg). Sulbutiamine did not modify memory in the DNMTS
      task but improved it in the object recognition task. Dizocilpine, impaired both
      acquisition and retention of the DNMTS task in the saline-treated group, but not
      in the two sulbutiamine-treated groups, suggesting that sulbutiamine may
      counteract the amnesia induced by a blockade of the N-methyl-D-aspartate
      glutamate receptors. Taken together, these results are in favor of a beneficial
      effect of sulbutiamine on working and episodic memory.

PMID- 15951088
TI  - Pharmacogenetics of the serotonin transporter.
AB  - Response to psychopharmacologic drugs is genetically complex, results from an
      interplay of multiple genomic variations with environmental influences, and
      depends on the structure or functional expression of gene products, which are
      direct drug targets or indirectly modify the development and synaptic plasticity
      of neural networks critically involved in their effects. During brain
      development, the serotonin (5HT) system, which is commonly targeted by
      antidepressant, anxiolytic, and antipsychotic drugs, controls neuronal
      specification, differentiation, and phenotype maintenance. While formation and
      integration of these neural networks is dependent on the action of multiple
      proteins, converging lines of evidence indicate that genetically controlled
      variability in the expression of the 5HT transporter (5HTT) is critical to the
      development and plasticity of distinct neurocircuits. The most promising finding
      to date indicate an association between the response time as well as overall
      response to serotonin reuptake inhibitors (SSRIs) and a common polymorphism
      (5HTTLPR) within the transcriptional control region of the 5HTT gene (SLC6A4) in
      patients with depressive disorders. The formation and maturation of serotonergic
      and associated systems, in turn, are influencing the efficacy of serotonergic
      compounds in a variety of psychiatric conditions. Based on the notion that
      complex gene x gene and gene x environment interactions in the regulation of
      brain plasticity are presumed to contribute to individual differences in
      psychopharmacologic drug response, the concept of developmental
      psychopharmacogenetics is emerging.

PMID- 15951089
TI  - Does clozapine decrease smoking?
AB  - McEvoy et al.'s study in 1999, which used cotinine levels but had limited power,
      suggested that clozapine treatment may be associated with a mild smoking decrease
      (particularly when plasma clozapine levels are > 150 ng/ml). Some naturalistic
      studies also suggest that clozapine treatment may be associated with a mild
      smoking decrease. The present study included 38 schizophrenic daily smokers from
      a double-blind clozapine trial. Five analyses were tested for significant
      decreases in plasma cotinine levels from a haloperidol baseline to: (1) the end
      of clozapine trials regarding clozapine doses (100, 300 or 600 mg/day), (2) the
      end of the clozapine trial where the highest plasma clozapine level was achieved,
      (3) the end of the clozapine trial where a clozapine level in the 150-450 ng/ml
      range was achieved, (4) the end of the first clozapine trial regardless of
      clozapine dose, and (5) the end of the last clozapine trial in the study. The
      first and straightforward analysis by dose showed no clozapine effects on
      smoking. The second and the third analyses (an attempt to mimic the design by
      McEvoy et al. [McEvoy, J.P., Freudenreich, O., Wilson, W.H., 1999. Smoking and
      therapeutic response to clozapine in patients with schizophrenia. Biol. Psychiat.
      46, 125-129.]) also indicated that there was not a significant effect of
      clozapine on smoking. The fourth and five analyses were also negative. None of
      the five analyses in our clozapine trial demonstrated that clozapine had major
      effects on smoking. This study cannot rule out that in some subjects, clozapine
      treatment may be associated with a small decrease in smoking. New prospective
      longitudinal studies using repeated cotinine and clozapine levels are needed to
      explore whether clozapine may reduce smoking in some patients.

PMID- 15951090
TI  - Long-term treatment of adjunctive quetiapine for bipolar mania.
AB  - This study evaluated the overall effectiveness and tolerability of adjunctive
      quetiapine as a continuation therapy for the long-term treatment of bipolar
      mania. Twenty-three patients were enrolled in this study and received quetiapine
      add-on treatment in combination with their existing or new mood stabilizers. The
      clinical assessment was carried out using the Young Mania Rating Scale (YMRS),
      Clinical Global Impression-severity(CGI-s), Hamilton Depression Rating Scale
      scores-17 item, Simpson-Angus Rating Scale and Barnes Akathisia Rating Scale at
      the baseline, 1, 4, 12 and 24 weeks. The YMRS and CGI-s decreased significantly
      from the baseline to the endpoint by 89.7% and 78.3%, respectively (p < 0.0001; p
      < 0.0001). By the end of the study, 22 patients showed at least 50% improvement
      in the YMRS score. This study suggests that quetiapine can be used as an adjunct
      in the long-term treatment of bipolar mania.

PMID- 15951091
TI  - Concentrations of N-methyl-2-pyrrolidone (NMP) and its metabolites in plasma and
      urine following oral administration of NMP to rats.
AB  - The primary aims were to study the metabolism in rats and to determine the
      biological levels after one oral developmentally toxic dose of N-methyl-2
      pyrrolidone (NMP), a widely used industrial chemical. Non-pregnant female Sprague
      Dawley rats were given an oral single dose of either a non-toxic dose of 125 mg
      NMP/kg (group 1) by gavage or a developmentally toxic dose of 500 mg/kg (group
      2). Blood plasma (7 rats per time point) and urine (10 rats per time point) were
      sampled up to 72 h after administration and analyzed using mass spectrometry. In
      both plasma and urine NMP, 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP), N
      methylsuccinimide and 2-hydroxy-N-methylsuccinimide (2-HMSI) and 2-pyrrolidone (2
      P) were identified. In urine 48% of the administered dose was recovered as 5-HNMP
      and 2-5% as 2-HMSI. The total recovery in urine was 53-59%. The peak
      concentrations for NMP in plasma were 1.2 and 6.9 mmol/l, 0.42 and 0.76 mmol/l
      for 5-HNMP, 0.07 and 0.31 mmol/l for MSI and for 2-HMSI the concentrations were
      0.02 and 0.05 mmol/l for groups 1 and 2, respectively. In summary, the same
      metabolites were found in rats as in humans and the biological levels were
      reported for NMP and its metabolites after oral exposure to a developmentally
      toxic dose and one non-toxic dose of NMP.

PMID- 15951092
TI  - The brain is a target organ after acute exposure to depleted uranium.
AB  - The health effects of depleted uranium (DU) are mainly caused by its chemical
      toxicity. Although the kidneys are the main target organs for uranium toxicity,
      uranium can also reach the brain. In this paper, the central effects of acute
      exposure to DU were studied in relation to health parameters and the sleep-wake
      cycle of adult rats. Animals were injected intraperitoneally with 144+/-10 microg
      DU kg-1 as nitrate. Three days after injection, the amounts of uranium in the
      kidneys represented 2.6 microg of DU g-1 of tissue, considered as a sub
      nephrotoxic dosage. The central effect of uranium could be seen through a
      decrease in food intake as early as the first day after exposure and shorter
      paradoxical sleep 3 days after acute DU exposure (-18% of controls). With a lower
      dosage of DU (70+/-8 microg DU kg-1), no significant effect was observed on the
      sleep-wake cycle. The present study intends to illustrate the fact that the brain
      is a target organ, as are the kidneys, after acute exposure to a moderate dosage
      of DU. The mechanisms by which uranium causes these early neurophysiological
      perturbations shall be discussed.

PMID- 15951093
TI  - Carbofuran and malathion inhibit nucleotide hydrolysis in zebrafish (Danio rerio)
      brain membranes.
AB  - Carbofuran and malathion are broad spectrum pesticides widely used in
      agricultural practice throughout the world. Toxicity of these pesticides has been
      correlated with their inhibitory effects on acetylcholinesterase activity.
      Nucleotides are extracellular signaling molecules, which trigger multiple
      biological effects. Studies have demonstrated the co-transmission of
      acetylcholine and ATP at the nerve endings. The control of neurotransmitter ATP
      levels is promoted by enzymes named ectonucleotidases, which include nucleoside
      triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. Since
      acetylcholine and ATP are co-released at the synapse and the acetylcholinesterase
      inhibition is an important target for pesticide action, here we verified the
      effect of exposure in vitro and in vivo to carbofuran and malathion on
      ectonucleotidase activities from brain membranes of zebrafish. To verify if
      carbofuran and malathion have a direct inhibitory effect on NTPDase and 5'
      nucleotidase activities in brain membranes of zebrafish, we have tested in vitro
      concentrations of pesticides varying from 0.25 to 5 mM. Carbofuran, in vitro,
      inhibited ATP and ADP hydrolysis in an uncompetitive manner, but no effect was
      observed on AMP hydrolysis. Malathion decreased ATP and ADP hydrolysis in
      competitive and an uncompetitive manner, respectively, but not altered AMP
      hydrolysis. After exposure to carbofuran (50 and 500 microg/L) during 7 days, ADP
      hydrolysis was significantly decreased in both concentrations tested (by 19 and
      24.5%, respectively). Malathion, at 500 microg/L, was able to inhibit ADP and AMP
      hydrolysis (by 28 and 58.5%, respectively). This study has shown that
      ectonucleotidases from brain membranes of zebrafish can be a potential target for
      pesticide neurotoxicity.

PMID- 15951094
TI  - Effects of bisphenol-A (BPA), dibutylphtalate (DBP), benzophenone-2 (BP2),
      procymidone (Proc), and linurone (Lin) on fat tissue, a variety of hormones and
      metabolic parameters: a 3 months comparison with effects of estradiol (E2) in
      ovariectomized (ovx) rats.
AB  - The endocrine active substances BPA, DBP and BP2 have estrogenic effects in the
      uterus. Proc and Lin were shown to be antiandrogenic. Whether other estrogen
      regulated parameters like lipids, fat metabolism and hormones are also affected
      by these substances is unknown. We compared the effects of a 3 months lasting
      administration of these substances with those of E2 on an estrogen-regulated fat
      depot and on serum TSH, T3, T4, LH, and lipid concentrations. BP2 shared many of
      the effects of E2 by suppressing LH, cholesterol, LDL, HDL and the size of a
      small estrogen-regulated fat depot in the lower hindleg. BP2 suppressed T4 but
      not T3 and TSH. The effects of DBP and BPA were mostly negligible whereas Lin and
      Proc also reduced the fat depot and serum leptin but increased triglycerides and
      serum lipids. Serum T3 and T4 concentrations were reduced by Lin and Proc. These
      data indicate that BP2 has similar, though slightly weaker effects as E2 whereas
      the effects of Proc and Lin differ from those of E2 on serum lipids and hormones.
      BP2 can be regarded as an estrogenic endocrine active substance whereas the
      effects of Lin and Proc appear not to involve estrogen receptors.

PMID- 15951095
TI  - MnSOD polymorphisms in sensitized patients with delayed-type hypersensitivity
      reactions to the chemical allergen para-phenylene diamine: a case-control study.
AB  - Dyes such as para-phenylene diamine (PPD) or related para-compounds are very
      common contact sensitizers in man. The corresponding contact dermatitis in
      sensitized individuals is a complex and common illness associated with
      considerable morbidity and social cost. It has been found that oxidative stress
      from reactive oxygen species (ROS) may play an important role in the pre
      immunological phase of allergic contact dermatitis to PPD. Manganese superoxide
      dismutase (MnSOD) is one of the primary enzymes that directly scavenge potential
      harmful oxidizing species. A valine (Val) to alanine (Ala) substitution at amino
      acid -9, occurring in the MnSOD gene, has been associated with various disease
      risk. The aim of our study was to investigate possible associations of the MnSOD
      47 T>C genotype in exon 2 (Ala-9Val) and the 339 T>C genotype in exon 3
      (Ile58Thr) with contact sensitization to PPD in humans in a case-control study.
      The study was performed in 157 unrelated cases and 201 age- and gender-matched
      controls. The MnSOD genotypes were determined using LightCycler allele
      discrimination assays. No heterozygous (CT) or homozygous carriers (TT) for the
      Ile58Thr polymorphism were found. The frequency for the C allele of the Ala-9Val
      polymorphism was 51% (79/157) in cases and 49% (107/201) in controls. Homozygous
      CC carriers (Ala/Ala) were 27% (43/157) in cases and 23% (46/201) in controls
      (odds ratio [OR], 1.3; 95% confidence interval [CI], 0.8-2.1). Stratification
      into subgroups based on gender and age limited the association to females.
      Increased risk among homozygous CC carriers (Ala/Ala) was only found in the group
      of older females (over 45 years, 25% versus 18%; OR, 1.5; 95% CI, 0.7-2.34).
      These data suggest that the C (Ala) allele of MnSOD modifies contact dermatitis
      risk among older females, but is not an independent susceptibility factor for
      contact sensitization to PPD.

PMID- 15951096
TI  - Bacterial efflux systems and efflux pumps inhibitors.
AB  - It is now well established that bacterial resistance to antibiotics has become a
      serious problem of public health that concerns almost all antibacterial agents
      and that manifests in all fields of their application. Among the three main
      mechanisms involved in bacterial resistance (target modification, antibiotic
      inactivation or default of its accumulation within the cell), efflux pumps,
      responsible for the extrusion of the antibiotic outside the cell, have recently
      received a particular attention. Actually, these systems, classified into five
      families, can confer resistance to a specific class of antibiotics or to a large
      number of drugs, thus conferring a multi-drug resistance (MDR) phenotype to
      bacteria. To face this issue, it is urgent to find new molecules active against
      resistant bacteria. Among the strategies employed, the search for inhibitors of
      resistance mechanisms seems to be attractive because such molecules could restore
      antibiotic activity. In the case of efflux systems, efflux pump inhibitors (EPIs)
      are expected to block the pumps and such EPIs, if active against MDR pumps, would
      be of great interest. This review will focus on the families of bacterial efflux
      systems conferring drug resistance, and on the EPIs that have been identified to
      restore antibiotic activity.

PMID- 15951097
TI  - Anandamide metabolism by Tetrahymena pyriformis in vitro. Characterization and
      identification of a 66 kDa fatty acid amidohydrolase.
AB  - Fatty acid amidohydrolase, a membrane-bound enzyme found in a variety of
      mammalian cells, is responsible for the catabolism of neuromodulatory fatty acid
      amides, including anandamide. In an earlier study we reported that Tetrahymena
      pyriformis was able to secrete a FAAH-like activity in starvation medium (Karava
      V., Fasia L., Siafaka-Kapadai A., FEBS Lett. 508 (2001) 327-331). In this study
      the endocannabinoid anandamide, was found to be metabolized by T. pyriformis
      homogenate by the action of a FAAH-like enzyme, in a time- and concentration
      dependent manner. The main metabolic products of [3H]anandamide hydrolysis were
      [3H]arachidonic acid and ethanolamine. Amidohydrolase activity was maximal at pH
      9-10, it was inhibited by phenylmethylsulfonyl fluoride and
      arachidonyltrifluoromethyl ketone and was Ca2+ and Mg(2+)-independent. Kinetic
      experiments demonstrated that the enzyme had an apparent K(m) of 2.5 microM and
      V(max) of 20.6 nmol/min mg. Subcellular fractionation of T. pyriformis homogenate
      showed that the activity was present in every subcellular fraction with highest
      specific activity in the microsomal as well as in non-microsomal membrane
      fraction. Immunoblot analysis of selected subcellular fractions, using an anti
      FAAH polyclonal antibody, revealed the presence of an immunoreactive protein with
      a molecular mass approximately 66 kDa similar to the molecular mass of the
      mammalian enzyme. In conclusion, this study demonstrates that a FAAH similar to
      the mammalian enzyme is present in a unicellular eukaryote, indicating the
      importance of FAAH activity throughout evolution. It also supports the notion
      that Tetrahymena species may be a suitable model for metabolic studies on
      endocannabinoids, as well as for the study of drugs targeted towards FAAH.

PMID- 15951098
TI  - Translational control during mitosis.
AB  - Translation is now recognized as an important process in the regulation of gene
      expression. During the cell cycle, translation is tightly regulated. Protein
      synthesis is necessary for entry into and progression through mitosis and
      conversely, modifications of translational activity are observed during the cell
      cycle. This review focuses on translational control during mitosis (or M-phase)
      and the role of CDK1/cyclin B, the universal cell cycle regulator implicated in
      the G2/M transition, in protein synthesis regulation.

PMID- 15951099
TI  - Histories of depression, allopregnanolone responses to stress, and premenstrual
      symptoms in women.
AB  - Twenty-six women meeting DSM criteria for premenstrual dysphoric disorder (PMDD)
      and 39 non-PMDD controls were tested for allopregnanolone (ALLO) responses to
      mental stress. Approximately half of each group had a history of depression (DEP)
      (14 PMDD, 17 non-PMDD), though all were free of current psychiatric illness. ALLO
      was sampled in response to venipuncture stress, after an extended baseline, and
      again 30 and 60 min following the onset of mental stressors. All women with prior
      DEP, regardless of PMDD status, showed a blunted ALLO stress response at 30 and
      60 min (p < 0.05), and also failed to show the expected decrease from
      venipuncture to baseline rest (p = 0.08) compared to women with no prior DEP.
      Women with prior DEP did not show the expected correlation between progesterone
      and ALLO (r = 0.16) that was seen in those with no prior DEP (r = 0.37, p <
      0.05). ALLO levels at extended baseline and blunted ALLO reactivity predicted
      more severe premenstrual symptoms, but only in PMDD women with prior DEP (p
      values <0.05). These results suggest that a history of DEP is associated with a
      failure of ALLO to be appropriately responsive to challenge, with alterations in
      the conversion of progesterone to ALLO, and confirm prior reports linking ALLO to
      symptoms in PMDD, but only in PMDD women with histories of DEP.

PMID- 15951100
TI  - Different platelet activation levels in non-pregnant, normotensive pregnant,
      pregnancy-induced hypertensive and pre-eclamptic women. A pilot study of flow
      cytometric analysis.

PMID- 15951101
TI  - A comparison of oral and vaginal misoprostol for induction of labor.
AB  - OBJECTIVE: The aim of the study is to compare the efficacy and safety of oral
      (100 microg) and vaginal (50 microg) misoprostol for labor induction. STUDY
      DESIGN: Ninety-nine patients with indications for labor induction randomly
      received 100 microg oral misoprostol every 4 h or 50 microg vaginal misoprostol
      every 4 h, using maximum six doses. Mean induction to delivery interval, mode of
      delivery, rates of tachysystole, hypertonus and hyperstimulation syndrome,
      oxytocin use, number of doses used, failed induction rate and neonatal outcomes
      were compared for the two groups. RESULTS: Mean dose of misoprostol used for oral
      and vaginal misoprostol groups were 2.17+/-1.35 and 1.91+/-0.94, respectively
      (p=0.65). There were two failed inductions in the oral (4%) and one failed
      induction (2.5%) in the vaginal group after a total of six doses of misoprostol
      (p=0.58). There was no significant difference for the mean induction to delivery
      interval, to the beginning of active phase interval, active phase duration,
      second stage duration and the number of women who received oxytocin for induction
      or augmentation between the two groups (p>0.05). There were also no significant
      differences for intrapartum complications and neonatal outcomes between the oral
      and vaginal misoprostol groups (p>0.05). CONCLUSION: Our findings indicate that,
      in a closely supervised hospital setting with adequate monitoring, 100 microg
      oral misoprostol has the potential to induce labor as safely and effectively as
      its 50 microg vaginal analogue. As oral use of the drug is easier for both the
      patient and the doctor, oral misoprostol will probably be more preferable than
      the vaginal route.

PMID- 15951102
TI  - Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA,
      ISSAM, and EAU recommendations.

PMID- 15951103
TI  - EXAMINE: a computational approach to reconstructing gene regulatory networks.
AB  - Reverse-engineering of gene networks using linear models often results in an
      underdetermined system because of excessive unknown parameters. In addition, the
      practical utility of linear models has remained unclear. We address these
      problems by developing an improved method, EXpression Array MINing Engine
      (EXAMINE), to infer gene regulatory networks from time-series gene expression
      data sets. EXAMINE takes advantage of sparse graph theory to overcome the
      excessive-parameter problem with an adaptive-connectivity model and fitting
      algorithm. EXAMINE also guarantees that the most parsimonious network structure
      will be found with its incremental adaptive fitting process. Compared to previous
      linear models, where a fully connected model is used, EXAMINE reduces the number
      of parameters by O(N), thereby increasing the chance of recovering the underlying
      regulatory network. The fitting algorithm increments the connectivity during the
      fitting process until a satisfactory fit is obtained. We performed a systematic
      study to explore the data mining ability of linear models. A guideline for using
      linear models is provided: If the system is small (3-20 elements), more than 90%
      of the regulation pathways can be determined correctly. For a large-scale system,
      either clustering is needed or it is necessary to integrate information in
      addition to expression profile. Coupled with the clustering method, we applied
      EXAMINE to rat central nervous system development (CNS) data with 112 genes. We
      were able to efficiently generate regulatory networks with statistically
      significant pathways that have been predicted previously.

PMID- 15951104
TI  - Detecting minimal residual disease in neuroblastoma patients-the present state of
      the art.
AB  - While cyto- and histological screening of bone marrow samples are still accepted
      as the gold standard for initial staging of neuroblastoma patients, these
      applications are insufficient during or after therapy because it is not always
      possible to detect tumour cell infiltration below the level of 1% by morphology
      alone. For monitoring of minimal residual disease, techniques offering a
      considerably higher sensitivity have been developed. Immunocytology, RT-PCR and
      flow cytometry are most frequently used, but differ with regard to targets
      (single cells, RNA transcripts), measured parameters (tumour cell number, antigen
      expression, cytomorphology, cytogenetic aberrations, level/number of RNA
      transcripts), specificity (uni-/multi-parameter analysis) and sensitivity (number
      of investigated cells). The pros and cons of these methods are reviewed. Precise
      quantification of residual tumour cells in bone marrow and blood may show a
      future impact on risk grouping and therapeutic strategies for patients with
      disseminated disease, but the potential clinical application of these techniques
      has to be preceded by thorough standardisation and validation in multi-centre
      studies.

PMID- 15951105
TI  - Lack of enhancing effects of sodium nitrite on 2-amino-1-methyl-6
      phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis in female
      Sprague-Dawley rats.
AB  - A number of heterocyclic amines (HCAs) have been shown to exert enhanced
      carcinogenic and mutagenic potential when given simultaneously with sodium
      nitrite (NaNO(2)). In the present experiment, effects of combined treatment with
      NaNO(2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), one of the
      most prevalent carcinogenic HCAs in the human environment, were assessed with
      regard to mammary tumor induction in female Sprague-Dawley (SD) rats. Animals at
      6 weeks of age were given intragastric doses of 100mg/kg body weight of PhIP
      twice a week for 4 weeks, during which period 0 or 0.2% NaNO(2) was administered
      in the drinking water. Control rats received 0.2% NaNO(2) alone for the 4 weeks
      or non-supplemented water during the entire 48 week experimental period, without
      carcinogen treatment. The first tumor in the PhIP+NaNO(2) group appeared
      significantly later than with PhIP alone, and during the experimental period, the
      incidence, multiplicity and volume of mammary tumors in this group tended towards
      decreased, although values did not significantly differ at the terminal
      sacrifice. These results indicate that NaNO(2) does not enhance PhIP-induced rat
      mammary carcinogenesis, rather possessing some potential for inhibition.

PMID- 15951106
TI  - Application of microarray-based technology to neuroblastoma.
AB  - In the past decade, microarray technology has become a major tool for high
      throughput comprehensive analysis of gene expression, genotyping and re
      sequencing applications. High-throughput microarrays are used for expression
      profiling analyses with the aims of gene or pathway discovery, tumor
      subclassification or relapse risk assessment. The introduction of microarray CGH
      provides a powerful tool to precisely detect and quantify genomic aberrations and
      map these directly onto the human genome. This review summarizes the current
      status of the application of microarray technology to neuroblastoma research.

PMID- 15951107
TI  - High-resolution cDNA microarray-based comparative genomic hybridization analysis
      in neuroblastoma.
AB  - Neuroblastoma (NB) is one of the most common pediatric solid tumors and displays
      a broad variety of genomic alterations. Array-based comparative genomic
      hybridization (A-CGH) is a novel technology enabling the high-resolution
      detection of DNA copy number aberrations. In this article, we outline features of
      this new technology and approaches of data analysis. We focus on stage specific
      DNA copy number variations in neuroblastoma detected by cDNA array-based
      comparative genomic hybridization (A-CGH). We also discuss hypothetic
      evolutionary models of neuroblastoma progression that can be derived from A-CGH
      data.

PMID- 15951108
TI  - Soy isoflavones modulate the expression of BAD and neuron-specific beta III
      tubulin in male rat brain.
AB  - Isoflavones, the most abundant phytoestrogens in soy foods, are structurally
      similar to 17beta-estradiol. There is evidence that soy isoflavones influence
      neuronal apoptosis or proliferation in vitro and in vivo. However, little
      research has been done to investigate the effects of soy isoflavones on markers
      of neuronal apoptosis and survival in vivo. We examined brain BAD (a proapoptotic
      member of Bcl-2 protein family) and neuron-specific beta III tubulin (an early
      marker of neuronal differentiation/survival) levels in male rats fed either a
      standard chow rich of soy isoflavones (Phyto-600) or one free of soy isoflavones
      (Phyto-free) life-long (from conception until time tissue collected). Among five
      brain regions, the expression of BAD was highest in medial basal hypothalamus
      (MBH); the next highest in hippocampus; moderate in amygdala and frontal cortex;
      and lowest in cerebellum in Phyto-free fed animals. In animals on Phyto-600 diet,
      the levels of BAD were significantly decreased in frontal cortex and MBH; but
      significantly increased in the amygdala. The expression of beta III tubulin was
      highest in frontal cortex; moderate in amygdala, hippocampus and MBH; and lowest
      in cerebellum in the Phyto-free group. In rats fed with the Phyto-600 diet,
      levels of beta III tubulin were significantly increased in amygdala, frontal
      cortex, hippocampus and MBH compared to Phyto-free values. In summary, these
      findings provide evidence for the neuroprotective potential of soy isoflavones in
      the amygdala, frontal cortex, hippocampus and MBH. This implies that consumption
      of soy isoflavones may be beneficial on learning and memory, anxiety-related
      behaviors, and recovery from trauma.

PMID- 15951109
TI  - The effect of a nitric oxide donor, sodium nitroprusside, on the release of
      acetylcholine from the in vitro cat carotid body.
AB  - The purpose of the present study was to determine the impact of a nitric oxide
      (NO) donor, sodium nitroprusside (SNP), on the release of acetylcholine (ACh), an
      essential excitatory neurotransmitter, from the in vitro cat carotid body (CB).
      Bilateral CBs were harvested from five deeply anesthetized cats according to the
      regulations contained in the policies of the Johns Hopkins Animal Care and Use
      Committee. After recovering from the surgical procedures for extraction and
      cleaning, the CBs were taken through a 15-step protocol in which they were
      exposed to a hyperoxic gas mixture (40% O2/5% CO2; 20 min), then a hypoxic gas
      mixture (6% O2/5% CO2; 20 min), and a final 10 min hyperoxic mixture. This
      sequence was applied twice, followed by the same sequence in the presence, first,
      of 5 microM SNP, and secondly in the presence of 10 microM SNP. After washing and
      a recovery period the CBs were again exposed to the gases as in the first two non
      SNP trials. The SNP exposures significantly reduced the overall release of ACh by
      about 20% (P=0.039). Further, SNP significantly reduced the hypoxia-induced
      increase in ACh release (without SNP: 82.4+/-19.1 fmol/20 microL versus with SNP:
      49.7+/-15.0 fmol/20 microL; mean+/-S.E.M.; P=0.032). Trials #1 and #2 which
      preceded the application of SNP and Trial #3 which followed SNP were
      statistically indistinguishable. The CBs had recovered their original status. The
      data support the hypothesis that the frequently reported NO-induced reduction in
      CB neural output during hypoxia is at least in part due to the reduction in ACh
      release. The results are consistent with a previous report in which l-arginine,
      an NO precursor, had the same reducing effect. Possible mechanisms are discussed.

PMID- 15951110
TI  - Intestinal electric stimulation modulates neuronal activity in the nucleus of the
      solitary tract in rats.
AB  - Intestinal electric stimulation (IES) has been shown to produce an inhibitory
      effect on gastric motility and secretion. The possible central mechanism of this
      entero-gastric inhibitory effect induced by IES is unknown. The objective of this
      study was to evaluate the effects of various IES on the activity of neurons in
      nucleus tractus solitarii (NTS). We examined the extracellular neuronal activity
      in NTS of the medulla in pentobarbital anesthetized, paralyzed, ventilated male
      adult rats. The aortic depressor, superior laryngeal, and carotid sinus nerves
      were crushed or sectioned bilaterally to avoid neuronal responses in NTS to
      cardiovascular baroreceptors. After NTS neurons with gastric input were
      identified, responses of single neurons in NTS to IES were determined. IES with
      different parameters was performed via a pair of platinum electrodes sutured onto
      the serosal surface of the duodenum 2 cm below the pylorus. IES with different
      parameters activated 39--72% of the solitary tract nucleus neurons responsive to
      gastric distension. Moreover, we demonstrated that IES activated the neuronal
      activity in NTS, which was stimulation energy dependent. The modulatory effect of
      IES on the central neurons receiving vagal inputs may contribute to the neural
      mechanisms of IES therapy for the treatment of patients with obesity and
      gastrointestinal motility disorders.

PMID- 15951111
TI  - First isolation and molecular characterization of Toxoplasma gondii from
      finishing pigs from Sao Paulo State, Brazil.
AB  - Toxoplasma gondii infection is widely prevalent in humans in Brazil. Among the
      food animals, pigs are considered the most important meat source of T. gondii for
      infection in humans. In the present study, we report the first isolation of
      viable T. gondii from finishing pigs in Brazil. Antibodies to T. gondii were
      found in 49 (17%) of 286 pigs prior slaughter using the modified agglutination
      test (MAT) at a serum dilution of 1:25. Attempts were made to isolate T. gondii
      from 28 seropositive pigs. Samples of heart, brain, and tongue from each pig were
      pooled, digested in acid pepsin, and bioassayed in five mice per pig. Viable T.
      gondii was isolated from seven pigs; all isolates were lethal for mice.
      Restriction fragment length polymorphism on products of SAG2 locus amplified by
      PCR revealed that two isolates were Type I and five were Type III. The results
      indicate that phenotypically and genetically T. gondii isolates from pigs from
      Brazil are distinct from isolates of T. gondii from pigs in the USA.

PMID- 15951112
TI  - Comparison of serological tests for equine trypanosomosis in naturally infected
      horses from Kazakhstan.
AB  - In this study, we compared the complement fixation test (CFT), the horse
      complement fixation test (HCFT) and a card agglutination test for trypanosomosis
      (CATT/T. evansi) for the diagnosis of equine trypanosomosis in the Republic of
      Kazakhstan. Cohen's kappa test was used to evaluate the concordance between the
      three tests. Kappa scores for CFT versus HCFT and CATT are both 0.6165 (95%
      Confidence Interval CI 0.414--0.819) indicating a "substantial" agreement between
      CFT and HCFT or CATT, respectively. Kappa for HCFT versus CATT is 0.395 (CI 0.142
      -0.648) indicating a "fair" agreement between the two tests. In the absence of a
      golden standard, seroprevalence and sensitivity and specificity of the three
      tests were estimated using maximum likelihood estimation. CFT has a sensitivity
      of 57.2% (CI 31.5--79.5%) and a specificity of 95.8% (CI 89.2--98.5%), HCFT has a
      sensitivity of 80.6% (CI 44.1--95.6%) and a specificity of 99.5% (CI 90.7--100%),
      CATT has a sensitivity of 80.2% (CI 44.5--95.2%) and a specificity of 98.5% (CI
      79.5--99.9%). The seroprevalence of equine trypanosomosis in Kazakhstan was
      estimated at 16.4% (CI 9.4--27.0%). The data suggest that for epidemiological
      studies and the control of equine trypanosomosis serological tests prove useful
      since they have a high specificity and a satisfactory sensitivity. Field
      applicable tests, such as CATT/T. evansi may be used to replace laboratory-based
      tests, such as CFT and HCFT.

PMID- 15951113
TI  - Linear and non-linear pressure dependence of enzyme catalytic parameters.
AB  - The pressure dependence of enzyme catalytic parameters allows volume changes
      associated with substrate binding and activation volumes for the chemical steps
      to be determined. Because catalytic constants are composite parameters,
      elementary volume change contributions can be calculated from the pressure
      differentiation of kinetic constants. Linear and non-linear pressure-dependence
      of single-step enzyme reactions and steady-state catalytic parameters can be
      observed. Non-linearity can be interpreted either in terms of interdependence
      between the pressure and other environmental parameters (i.e., temperature,
      solvent composition, pH), pressure-induced enzyme unfolding, compressibility
      changes and pressure-induced rate limiting changes. These different situations
      are illustrated with several examples.

PMID- 15951114
TI  - Mechanisms of cell membrane electropermeabilization: a minireview of our present
      (lack of ?) knowledge.
AB  - Cell electropulsation is routinely used in cell Biology for protein, RNA or DNA
      transfer. Its clinical applications are under development for targeted drug
      delivery and gene therapy. Nevertheless, the molecular mechanisms supporting the
      induction of permeabilizing defects in the membrane assemblies remain poorly
      understood. This minireview describes the present state of the investigations
      concerning the different steps in the reversible electropermeabilization process.
      The different hypotheses, which were proposed to give a molecular description of
      the membrane events, are critically discussed. Other possibilities are then
      given. The need for more basic research on the associated loss of cohesion of the
      membrane appears as a conclusion.

PMID- 15951115
TI  - Adaptation to extreme environments: macromolecular dynamics in complex systems.
AB  - What we previously thought of as insurmountable physical and chemical barriers to
      life, we now see as yet another niche harbouring 'extremophiles'. Extremophiles
      and their macromolecules had to develop molecular mechanisms of adaptation to
      extreme physico-chemical conditions. Using neutron spectroscopy, we have
      demonstrated that molecular dynamics represents one of these molecular mechanisms
      of adaptation. To which extent do hyper-saline conditions and extreme
      temperatures influence molecular dynamics? First, molecular dynamics were
      analysed for halophilic malate dehydrogenase from Haloarcula marismortui (Hm
      MalDH) under different molar solvent salt concentration conditions influencing
      its stability. Secondly, mean macromolecular motions were measured in-vivo in
      psychrophile (Aquaspirillum arcticum), mesophile (Escherichia coli and Proteus
      mirabilis), thermophile (Thermus thermophilus), and hyperthermophile (Aquifex
      pyrofilus) bacteria. The mean constant force of Hm MalDH increases progessively
      with increasing stability. The results show that the molecular adaptation of Hm
      MalDH to hyper-saline conditions is achieved through an increasing resilience of
      its structure dominated by enthalpic mechanisms. The study of bacteria has
      provided tools to quantify the macromolecular adaptation to extreme temperatures
      in the naturally crowded environment of the cell. The macromolecular resilience
      of bacteria increases with adaptation to high temperatures.

PMID- 15951116
TI  - Rapid identification of Candida species by FT-IR microspectroscopy.
AB  - Due to the continuous increase of human candidiasis and the great diversity of
      yeasts of the Candida genera, it is indispensable to identify this yeast as early
      as possible. Early identification enables an early diagnostic and patient-adapted
      anti-fungal therapy, thus reducing morbidity and mortality related to these
      infections. In view of this, we have in this study investigated microcolonies
      using a method based on Fourier transform-infrared microspectroscopy (FTIRM) for
      a rapid and early identification of the most frequent Candida species encountered
      in human pathology. FTIR spectroscopy is a whole-cell "fingerprinting" method by
      which microorganisms can be identified. By exploiting the huge discriminating
      capacity of this technique, we identified 6 species (Candida albicans, Candida
      glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei, and Candida
      kefyr) from a collection of 57 clinical strains of Candida, isolated from
      hospitalised patients. Data obtained on 10- to 18-h-old microcolonies were
      compared to cultures of 24 h. Our results clearly show the efficiency and the
      robustness of FTIR (micro)spectroscopy in identifying species with a
      classification rate of 100% for both microcolonies and 24-h cultures. FTIR
      microspectroscopy is thus a promising clinical approach, because compared to
      conventional and molecular techniques, it is time and money saving, has great
      identification and discriminating potentials, and is amenable to an automated
      high-throughput routine system.

PMID- 15951117
TI  - Radiotherapeutic management of brain metastases: a systematic review and meta
      analysis.
AB  - BACKGROUND: The management of brain metastases is a significant health care
      problem. An estimated 20-40% of cancer patients will develop metastatic cancer to
      the brain during the course of their illness. METHODS: A systematic review of
      randomized trials on adult cancer patients with single or multiple brain
      metastases from cancer of any histology was conducted. Eligible studies
      investigated external beam radiotherapy or radiosurgery in one of the study arms.
      Outcomes of interest included survival, intracranial progression-free duration,
      response of brain metastases to therapy, quality of life, symptom control,
      neurological function, and toxicity. RESULTS: Twenty-seven trials were included
      in this systematic review of the evidence. Pooled results from three randomized
      trials of surgical excision combined with whole brain radiotherapy (WBRT) showed
      no improvement in overall survival as compared to WBRT alone in patients with
      single brain metastasis. One randomized study of postoperative WBRT following
      excision of a single brain metastasis versus surgery alone detected a significant
      reduction in intracranial tumour recurrence rates but no corresponding difference
      in overall survival. Nine trials of altered dose-fractionation schedules compared
      to a standard control fractionation schedule (3000 cGy in 10 fractions) of WBRT
      showed no difference in probability of survival at 6 months. The addition of
      radiosensitizers, as assessed in five trials, did not confer additional benefit
      to WBRT in terms of overall survival or the frequency of brain metastases
      response. Three trials examined the use of WBRT and radiosurgery boost versus
      WBRT alone in selected patients with brain metastases. Overall survival did not
      improve for patients with multiple brain metastases. However, one trial reported
      an improvement in survival for patients with single brain metastasis treated with
      WBRT and radiosurgery boost. One older randomized trial examined the use of WBRT
      versus supportive care alone (using oral prednisone). Results were not
      conclusive. CONCLUSION: For patients with a single brain metastasis, good
      performance status, and minimal or no evidence of extracranial disease, surgical
      excision and postoperative WBRT improves survival (as compared to WBRT alone).
      There may be a small survival advantage associated with the use of radiosurgery
      boost and WBRT as compared to WBRT alone in selected patients with a single brain
      metastasis. There is no difference in overall survival or in neurologic function
      improvement with the use of altered whole brain dose-fractionation schedules as
      compared to standard fractionation schedules (3000 cGy in 10 fractions or 2000
      cGy in 5 fractions). There is no survival benefit associated with the use of
      radiosurgery boost and WBRT versus WBRT alone in patients with multiple brain
      metastases. Currently, neither chemotherapy nor radiosensitizers show a clear
      benefit in the objective parameters of survival and progression-free survival.
      For patients with poor performance status and active extracranial disease,
      steroids and supportive care are an option.

PMID- 15951118
TI  - Hodgkin Lymphoma in adolescents.
AB  - With the development of an integrated treatment approach, the cure rate and
      survival of patients with Hodgkin Lymphoma (HL) is now high. Treatment tailored
      to stage, using chemotherapy, with or without involved field radiotherapy is the
      standard of care. Paediatric oncologists have been developing treatment regimens
      to maximise cure rate whilst trying to minimise the associated late side-effects,
      and cure rates in children are now often greater than 90%. It has been suggested
      that the outcome of adolescents with HL does not match that of younger children,
      but published data focusing on this group of patients is scarce. Future treatment
      strategies may direct the treatment of adolescents with HL away from the current
      "adult" regimens, and closer to that currently received by children, but
      prospective randomised trials are required. Rationalisation of both chemotherapy
      and radiotherapy administered to children and adolescents aims to minimise the
      risk of significant long-term side effects without sacrificing high cure rates.
      Infertility, secondary malignancies, cardiac and respiratory morbidity are all
      significant risks of current combined modality treatment that need to be
      discussed when obtaining informed consent and may influence the choice of
      treatment offered or accepted. Monitoring late effects of treatment (both
      physical and psychological) is especially important in this group of young
      patients.

PMID- 15951119
TI  - Synaptic and subcellular localization of A-kinase anchoring protein 150 in rat
      hippocampal CA1 pyramidal cells: Co-localization with excitatory synaptic
      markers.
AB  - Excitatory and inhibitory ionotropic receptors are regulated by protein kinases
      and phosphatases, which are localized to specific subcellular locations by one of
      several anchoring proteins. One of these is the A-kinase anchoring protein
      (AKAP150), which confers spatial specificity to protein kinase A and protein
      phosphatase 2B in the rat brain. The distribution of AKAP150 was examined at rat
      hippocampal CA1 pyramidal cell asymmetric and symmetric post-synaptic densities
      and with respect to the distribution of markers of excitatory (vesicular
      glutamate transporter 1, glutamate receptor subunit 1) and inhibitory receptors
      (vesicular GABA transporter, GABA receptor type A beta2/3 subunits, gephyrin) and
      the Golgi marker, trans-Golgi network glycoprotein 38. AKAP150 was close to
      asymmetric synapses, consistent with numerous molecular and biochemical studies
      suggesting its interaction with components of the excitatory postsynaptic
      density. In contrast, we did not find AKAP150-immunoreactivity associated with
      inhibitory synapses in rat CA1 neurons, despite reports demonstrating an in vitro
      interaction between AKAP150 and GABA receptor type A receptor beta subunits, and
      the reported co-localization of these proteins in rat hippocampal cultures. There
      was some overlap between AKAP150 and GABA receptor type A receptor beta2/3
      immunoreactivity intracellularly in perinuclear clusters. These findings support
      previous work indicating the integration of kinase and phosphatase activity at
      excitatory synapses by AKAP150, but do not support a role for selective targeting
      of AKAP150 and its accompanying proteins to inhibitory synapses.

PMID- 15951121
TI  - Facilitation of conditioned fear extinction by d-cycloserine is mediated by
      mitogen-activated protein kinase and phosphatidylinositol 3-kinase cascades and
      requires de novo protein synthesis in basolateral nucleus of amygdala.
AB  - Recent results showed that either systemic or intra-amygdala administration of d
      cycloserine, a partial agonist at the glycine modulatory site on the glutamate N
      methyl-d-aspartate receptor facilitates the extinction of conditioned fear. Here
      we evaluated the role of mitogen-activated protein kinase and
      phosphatidylinositol 3-kinase in the basolateral nucleus of amygdala on the
      effect of d-cycloserine. The facilitation effect of d-cycloserine on fear
      extinction and mitogen-activated protein kinase activation was completely blocked
      by intra-amygdala administration of mitogen-activated protein kinase inhibitor
      PD98059 (500 ng/side, bilaterally) or U0-126 (20 microM/side, bilaterally).
      Furthermore, phosphatidylinositol 3-kinase inhibitor (wortmannin, 5.0
      microg/side, bilaterally) infused into the basolateral nucleus of amygdala
      significantly reduced both facilitation effect of d-cycloserine and
      phosphatidylinositol 3-kinase activation. Intra-amygdala administration of a
      transcription inhibitor (actinomycin D, 10 microg dissolved in 1.6 microl
      vehicle; 0.8 microl per side) and a translation inhibitor (anisomycin, 125 microg
      dissolved in 1.6 microl vehicle; 0.8 microl per side) completely blocked the
      facilitation effect of d-cycloserine. Control experiments indicated the blockage
      by actinomycin D or anisomycin were not due to lasting damage to the basolateral
      nucleus of amygdala or state dependency. In addition, none of the active drugs
      used here altered the expression of conditioned fear. These results suggested
      that phosphatidylinositol 3-kinase and mitogen-activated protein kinase-dependent
      signaling cascades and new protein synthesis within the basolateral nucleus of
      amygdala played important roles in the d-cycloserine facilitation of the
      extinction of conditioned fear.

PMID- 15951120
TI  - Basic fibroblast growth factor stimulates functional recovery after neonatal
      lesions of motor cortex in rats.
AB  - Rats were given bilateral lesions of the motor cortex on the tenth day of life,
      and then received a daily subcutaneously injection of either basic fibroblast
      growth factor (FGF-2) or vehicle for 7 consecutive days. In adulthood, they were
      trained and assessed on a skilled forelimb reaching task. Although all lesion
      groups were impaired at skilled reaching, the postnatal day 10-lesioned group
      that received FGF-2 was less impaired than the lesion group that received the
      vehicle. Furthermore, the lesioned rats that received FGF-2 showed a filling of
      the lesion cavity with tissue, whereas the lesioned vehicle-treated rats still
      had a prominent lesion cavity. The functionality of the tissue filling the
      cavity, tissue surrounding it, and tissue from the motor cortex (in control rats)
      was assessed using intracortical microstimulation, and showed that stimulation of
      some sites from the filled cavity could evoke movement. The rats were perfused
      and processed for Golgi-Cox staining. Medium spiny neurons from the striatum were
      drawn and analyzed, and the results suggest that postnatal day 10 lesions of the
      motor cortex induced an increase in the length and complexity of these cells
      compared with those of non-lesioned rats. Our results suggest that FGF-2 may play
      an important role in recovery from early brain damage.

PMID- 15951122
TI  - Cardiomyopathy in streptozotocin-induced diabetes involves intra-axonal
      accumulation of calcitonin gene-related peptide and altered expression of its
      receptor in rats.
AB  - Calcitonin gene-related peptide (CGRP) is a vasorelaxant and positive inotropic
      and chronotropic peptide that binds to the calcitonin receptor-like receptor. In
      the heart, upon stimulation CGRP is released from sensory nerve terminals and
      improves cardiac perfusion and function. In the present study, we investigated
      alterations in the components of the CGRP signaling system during development of
      diabetic cardiomyopathy. Rats received a single injection of streptozotocin.
      Four, 8, and 16 weeks thereafter cardiac CGRP content (radioimmunoassay),
      calcitonin receptor-like receptor expression (by real-time RT-PCR), and CGRP and
      calcitonin receptor-like receptor tissue distribution (immunohistochemistry) were
      assessed. CGRP content of atria and ventricles progressively increased during the
      4 months following streptozotocin-treatment, while the distribution of CGRP
      immunoreactive fibers was not visibly altered. Conversely, cardiac expression of
      calcitonin receptor-like receptor initially (4 weeks after treatment) increased
      but then gradually declined to 47% of control levels in both atria after 16
      weeks. These quantitative changes were not associated with altered cellular
      distribution patterns (primarily in venous and capillary endothelium). Since
      sensory neurons have been reported to decrease expression of the CGRP precursor
      in the course of diabetes, the intra-axonal accumulation of CGRP observed here
      reflects impaired release, which, coupled with the down-regulation of its cognate
      receptor, calcitonin receptor-like receptor, may contribute to the well
      documented impairment of cardioprotective functions in diabetes.

PMID- 15951123
TI  - Altered expression of GABA(A) and GABA(B) receptor subunit mRNAs in the
      hippocampus after kindling and electrically induced status epilepticus.
AB  - Epilepsy may result from altered transmission of the principal inhibitory
      transmitter GABA in the brain. Using in situ hybridization in two animal models
      of epileptogenesis, we investigated changes in the expression of nine major
      GABA(A) receptor subunits (alpha1, alpha2, alpha4, alpha5, beta1-beta3, gamma2
      and delta) and of the GABA(B) receptor species GABA(B)R1a, GABA(B)R1b and
      GABA(B)R2 in 1) hippocampal kindling and 2) epilepsy following electrically
      induced status epilepticus (SE). Hippocampal kindling triggers a decrease in
      seizure threshold without producing spontaneous seizures and hippocampal damage,
      whereas the SE model is characterized by spontaneous seizures and hippocampal
      damage. Changes in the expression of GABA(A) and GABA(B) receptor mRNAs were
      observed in both models, and compared with those seen in other models and in
      human temporal lobe epilepsy. The most prominent changes were a relatively fast
      (24 h after kindling and electrically-induced SE) and lasting (7 and 30 days
      after termination of kindling and SE, respectively) reduction of GABA(A) receptor
      subunit delta mRNA levels (by 43-78%) in dentate granule cells, accompanied by
      increases in mRNA levels of all three beta-subunits (by 8-79%) and subunit gamma2
      (by 11-43%). Levels of the minor subunit alpha4 were increased by up to 60% in
      dentate granule cells in both animal models, whereas those of subunit alpha5 were
      decreased 24 h and 30 days after SE, but not after kindling. In cornu ammonis 3
      pyramidal cells, downregulation of subunits alpha2, alpha4, alpha5, and beta1-3
      was observed in the ventral hippocampus and of alpha2, alpha5, beta3 and gamma2
      in its dorsal extension 24 h after SE. Similar but less pronounced changes were
      seen in sector cornu ammonis 1. Persistent decreases in subunit alpha2, alpha4
      and beta2 transcript levels were presumably related to SE-induced cell loss.
      GABA(B) receptor expression was characterized by increases in GABA(B)R2 mRNA
      levels at all intervals after kindling and SE. The observed changes suggest
      substantial and cell specific rearrangement of GABA receptors. Lasting
      downregulation of subunits delta and alpha5 in granule cells and transient
      decreases in subunit alpha2 and beta1-3 mRNA levels in cornu ammonis 3 pyramidal
      cells are suggestive of impaired GABA(A) receptor-mediated inhibition. Persistent
      upregulation of subunits beta1-3 and gamma2 of the GABA(A) receptor and of
      GABA(B)R2 mRNA in granule cells, however, may result in activation of
      compensatory anticonvulsant mechanisms.

PMID- 15951124
TI  - Social reciprocity and health: new scientific evidence and policy implications.
AB  - The work contract is based on the norm of social reciprocity where appropriate
      rewards are provided for efforts and achievements at work. The effort-reward
      imbalance model of work stress maintains that contractual non-reciprocity in
      terms of high efforts spent and low rewards received is frequent if people have
      no alternative choice in the labour market, if they are exposed to heavy
      competition or if they are intrinsically motivated to engage in excessive work
      related commitment. According to the model, long-term exposure to effort-reward
      imbalance increases the risk of stress-related disorders. An overview of results
      from prospective epidemiological investigations testing the model is given.
      Overall, people who experience failed reciprocity at work are twice as likely to
      suffer from incident cardiovascular disease, depression or alcohol dependence
      compared to those who are not exposed. Associations are stronger for men than for
      women. Policy implications of findings for improved worksite health promotion are
      discussed.

PMID- 15951125
TI  - Cocaine dependence and PTSD: a pilot study of symptom interplay and treatment
      preferences.
AB  - Cocaine dependence and posttraumatic stress disorder (PTSD) frequently co-occur.
      Little is known, however, about patients' perceptions of symptom connectedness
      and preferences for treatment. This pilot study preliminarily investigated
      perceptions of symptom interplay and preferences regarding concurrent or
      sequential models of psychotherapy, therapy format, and treatment modalities.
      Participants were 23 individuals with current cocaine dependence and PTSD. The
      majority (95.5%) reported a functional relationship between cocaine use and PTSD
      symptoms (p<0.001). Improvement in PTSD symptoms was typically (63.6%) associated
      with a decrease in cocaine use (p<0.01). Similarly, a worsening of PTSD symptoms
      was typically (86.4%) associated with an increase in cocaine use (p<0.001). In
      contrast, improvement/deterioration in cocaine use was not significantly related
      to subsequent improvement/deterioration in PTSD symptoms. This finding suggests
      that changes in PTSD may be an important risk factor to consider among
      individuals with cocaine dependence and PTSD. Approximately 41% preferred a
      concurrent model of therapy in which the cocaine use and PTSD are treated
      simultaneously in therapy. The findings highlight the functional relationship
      between these two disorders and have direct implications for treatment
      interventions.

PMID- 15951126
TI  - Gender related effects of heroin abuse on the simple reaction time task.
AB  - Accumulated studies have demonstrated that there are serious negative
      consequences of drug abuse, especially the impairment of central nervous system
      (CNS) function. The simple reaction time (SRT) is the simplest model of measuring
      the function of the CNS. The purpose of the present study is to examine whether
      the SRT is affected by heroin abuse and whether such drug effect, if exists, is
      gender related. We found significant slowing of the SRT in both male and female
      heroin dependent patients at 1-3 months from withdrawal. However, the SRT slowing
      remitted after 3 months of abstinence in heroin dependent males but not in
      females. Our results suggested that the SRT is slowed by heroin abuse and such
      slowing is gender related.

PMID- 15951127
TI  - The absence of benzodiazepine craving in a general practice benzodiazepine
      discontinuation trial.
AB  - This study aimed to assess benzodiazepine craving longitudinally and to describe
      its time course by means of the Benzodiazepine Craving Questionnaire (BCQ).
      Subjects were long-term benzodiazepine users participating in a two-part
      treatment intervention aimed to reduce long-term benzodiazepine use in general
      practice in The Netherlands. Four repeated measurements of benzodiazepine craving
      were taken over a 21-month follow-up period. Results indicated that (1)
      benzodiazepine craving severity decreased over time, (2) patients still using
      benzodiazepines experienced significantly more severe craving than patients who
      had quit their use after one of the two interventions, and (3) the way in which
      patients had attempted to quit did not influence the experienced craving severity
      over time, however, (4) patients who had received additional tapering off, on
      average, reported significantly more severe craving than patients who had only
      received a letter as an incentive to quit. Although benzodiazepine craving is
      prevalent among (former) long-term benzodiazepine users during and after
      discontinuation, craving severity decreases over time to negligible proportions.
      Self-reported craving can be longitudinally monitored and quantified by means of
      the BCQ.

PMID- 15951128
TI  - Social anxiety, alcohol expectancies, and self-efficacy as predictors of heavy
      drinking in college students.
AB  - Burke and Stephens (1999) [Burke, R.S., Stephens, R.S. Social anxiety and
      drinking in college students: A social cognitive theory analysis. Clinical
      Psychology Review, 19, (1999) 513-530.] proposed a social cognitive theory of
      heavy drinking in college students. According to this theory, alcohol
      expectancies for social facilitation and self-efficacy for refusing heavy
      drinking in anxiety-producing social situations moderate the relationship between
      social anxiety and drinking. In the current study, a significant three-way
      interaction was observed among social anxiety, expectancies, and self-efficacy
      when amount and frequency of drinking was the dependent variable. As predicted by
      the model, socially anxious college students with low self-efficacy for avoiding
      heavy drinking in social situations and high positive expectancies for social
      facilitation reported more alcohol consumption than other socially anxious
      individuals.

PMID- 15951129
TI  - Attention and adolescent tobacco use: A potential self-regulatory dynamic
      underlying nicotine addiction.
AB  - Examines the covariation of attention processes in childhood and adolescence with
      tobacco use in middle adolescence, controlling for both comorbid antisocial
      behavior and psychosocial risk. Childhood ratings of inattention increased the
      risk of early-onset smoking (odds ratio = 4.12). During adolescence, high
      performance on an attention task was associated with increased risk (odds ratio =
      2.07) for patterned tobacco use after controlling for antisocial behavior and
      known psychosocial risk factors. These analyses suggest a possible regulatory
      dynamic linking patterned tobacco use and inattention. Given the role of
      attention in the regulation of negative affect, it is possible that tobacco use
      among vulnerable youth results in enhanced sense of well-being, compared to less
      vulnerable youth. Future research requires repeated assessments of attention,
      affective states and tobacco use to clarify issues of temporal ordering.

PMID- 15951130
TI  - Gender differences in the dihydropyrimidine dehydrogenase expression may
      contribute to higher toxicity in women treated with 5-fluorouracil therapy.

PMID- 15951131
TI  - The use of complex phosphates to inhibit tumour cell multiplication.

PMID- 15951132
TI  - Osteoporosis, a unitary hypothesis of collagen loss in skin and bone.
AB  - Progress in osteoporosis has been stultified by repetitive, statistic-driven
      studies and catechistic reviews; in the absence of concept and hypothesis
      research is aimless, and the trivial associations it continually reveals, has led
      to the cul-de-sac of multifactorialism. A return to hypothesis-led research which
      seeks major causal defects and the conclusive therapies that arise from them is
      essential. The hypothesis proposed evolved from research into the mechanism of
      senile purpura. This predicted a causal loss of skin collagen that was contrary
      to contemporary opinion, but was confirmed when collagen was expressed
      absolutely, instead as a percentage or ratio: women have less collagen than men
      and it decreases by 1% a year in exposed and unexposed skin. Corticosteroids
      (which also produce shear purpura) reduce skin collagen and androgen and virilism
      increase it; growth hormone produces the greatest increase, and there is a
      decrease in hypopituitarism. All these changes in skin collagen correspond to
      changes in bone density, and the circumstances are too various for coincidence.
      This led to the hypothesis that the changes found in skin collagen also occur in
      bone collagen, leading to the associated changes in bone density; thus a loss of
      collagen in skin and bones with aging is the causal counterpart to loss of bone
      density in senile osteoporosis. If this is correct then, as with aging, androgen
      and virilisation, corticosteroids, growth hormone and hypopituitarism, changes in
      bone density should correspond to systemic changes in skin collagen. This
      correspondence is found to occur in osteogenesis imperfecta and Ehlers-Danlos
      syndrome, two genetically discrete families of disordered collagen production,
      and other situations, e.g., scurvy and homocystinuria. A primary loss of collagen
      in osteoporotic bones is an essential prediction of the hypothesis; in fact this
      loss is well established but, inexplicably, it has been assumed to be secondary
      to the bone loss. Because of the comparable changes in skin and bones, the
      hypothesis implies that skin collagen could be used to predict the state of the
      bones and their response to treatment. It also implies androgen should be an
      effective treatment of osteoporosis, and growth hormone even more effective
      (likewise, of course, skin aging). More importantly, skin collagen and the
      production of collagen by skin fibroblasts could be used for the assay and
      industrial development of more potent, if not less toxic treatments and
      prevention of loss of bone (and skin) substance.

PMID- 15951133
TI  - Case report: the medical treatment of obstructive sleep apnoea syndrome (OSAS)
      with Selenium.

PMID- 15951134
TI  - Can the combination of localized "proliferative therapy" with "minor ozonated
      autohemotherapy" restore the natural healing process?
AB  - Regenerative injection therapy (RIT), also known as proliferative therapy, has
      been used for over 30 years in the USA in patients with spinal and peripheral
      joint and ligamentous pathologies. It involves the injection of mildly irritating
      medications onto ligaments and tendons, most commonly at origins and insertions.
      These injections cause a mild inflammatory response which "turns on" the normal
      healing process and results in the regeneration of these structures. At the same
      time they strengthen and become less sensitive to pain through a combination of
      neurolysis of small nerve fibers (C-fibers) and increased stability of the
      underlying structures. Oxygen/ozone therapy is a well established complementary
      therapy practiced in many European countries. The ozone dissolves in body fluids
      and immediately reacts with biomolecules generating messengers responsible for
      biological and therapeutic activities. This results in an anti inflammatory
      response, which also results in a similar trophic reaction to that of RIT. It is
      logical to expect that combining these two modalities would result in enhanced
      healing and therefore improved clinical outcomes. Oxygen/ozone therapy,
      accomplished by autohemotherapy (AHT), is performed by either administering
      ozonated blood intravenously (Major AHT) or via intramuscular route (Minor AHT).
      These procedures result in stimulation of the immune and healing systems. Our
      concept is that the local injection of this activated blood injected directly to
      the ligamentous areas that are also being treated with RIT will act as a direct
      stimulation to the healing process. In addition, combining this with intravenous
      major AHT should stimulate the immune system to augment and support this process.
      RIT and oxygen/ozone therapy have been extensively studied separately. We propose
      a study of lumbosacral ligamentous pain to explore this therapeutic combination.
      We hope that this paper will stimulate general interest in this area of medicine
      and result in investigation of the "interface" between these treatment
      modalities.

PMID- 15951135
TI  - The novel atypical antipsychotic aripiprazole as treatment for and prophylaxis
      against progressive multifocal leukoencephalopathy.

PMID- 15951136
TI  - Terpenoids from Picris echoides.
AB  - A new monoterpenoid glycoside, named (-)-cis-chrysanthenol-beta-D
      galactopyranoside (1), was isolated from the air-dried parts of Picris echoides
      along with the known compounds (-)-cis-chrysanthenol and 1alpha-hydroxyeudesma
      2,4(15),11(13)-trien-5alpha,7alphaH-12-oic acid.

PMID- 15951137
TI  - Antimicrobial activity of saponins from Acacia auriculiformis.
AB  - Acaciaside A and B, two acylated bisglycoside saponins originally isolated from
      the funicles of Acacia auriculiformis, are known to have antihelminthic activity.
      Their antifungal and antibacterial activities were investigated. Complete
      inhibition of conidial germination of Aspergillus ochraceous and Curvularia
      lunata was recorded at 300 microg/ml or less whereas to inhibit the growth of
      Bacillus megaterium, Salmonella typhimurium and Pseudomonas aeruginosa 700
      microg/ml or higher concentrations of the mixture was required. Two catabolic
      enzymes, phosphofructokinase and isocitrate dehydrogenase, responded
      differentially in fungi and bacteria against sublethal concentrations of the
      compound when assayed from their cell free extracts. An increased specific
      activity of the enzymes in bacteria and a decrease activity in fungi indicate a
      possible different mechanism of inhibition of saponins on the organisms tested.

PMID- 15951138
TI  - Giardia intestinalis: molecular characterization of UDP-N-acetylglucosamine
      pyrophosphorylase.
AB  - The flagellated protozoan Giardia intestinalis is one of the most prevalent human
      infective parasites with a worldwide distribution. This parasite must encyst to
      complete the life cycle and N-acetylgalactosamine is produced from endogenous
      glucose for cyst wall synthesis during the transformation. UDP-N
      acetylglucosamine pyrophosphorylase in G. intestinalis (GiUAP, EC 2.7.7.23) is
      the fourth enzyme in the inducible pathway of N-acetylgalactosamine biosynthesis,
      catalysing the conversion of N-acetylglucosamine-1-P to UDP-N-acetylglucosamine.
      In this study the gene GiUAP was cloned and sequenced from the Portland 1 strain
      using PCR techniques. It has an ORF of approximately 1.3 kb and contains no
      introns. BLAST and ClustalW analysis of the deduced amino acid sequence revealed
      significant similarities to other eukaryotic UAPs with putative active sites
      identified. Southern hybridization showed that GiUAP exists as a single-copy gene
      and it was shown to have two transcripts by RT-PCR and Northern hybridization.
      RLM-RACE identified both 5' and 3' untranslated regions and suggested the
      transcripts exist as a 5'-capped mRNA, with the use of two tandem polyadenylation
      sites to generate two unusually long giardial 3' untranslated regions of
      approximately 522 bp and approximately 3 kb. Moreover, a recombinant protein
      (rGiUAP) was expressed in E. coli and subjected to physical characterizations.
      Surprisingly the results obtained in this study were significantly different from
      those reported for the GiUAP in MR4 strain, suggesting this gene is under
      different transcription control in different strains of G. intestinalis. This
      report describes the molecular characterization of GiUAP and provides an
      opportunity to explore the control of gene expression during encystation of the
      parasite.

PMID- 15951139
TI  - Chromosomal rearrangements are associated with higher rates of molecular
      evolution in mammals.
AB  - Evolutionary rates are not uniformly distributed across the genome. Knowledge
      about the biological causes of this observation is still incomplete, but its
      exploration has provided valuable insight into the genomical, historical and
      demographical variables that influence rates of genetic divergence. Recent
      studies suggest a possible association between chromosomal rearrangements and
      regions of greater divergence, but evidence is limited and contradictory. Here,
      we test the hypothesis of a relationship between chromosomal rearrangements and
      higher rates of molecular evolution by studying the genomic distribution of
      divergence between 12,000 human-mouse orthologous genes. Our results clearly show
      that genes located in genomic regions that have been highly rearranged between
      the two species present higher rates of synonymous (0.7686 vs. 0.7076) and non
      synonymous substitution (0.1014 vs. 0.0871), and that synonymous substitution
      rates are higher in genes close to the breakpoints of individual rearrangements.
      The many potential causes of such striking are discussed, particularly in the
      light of speciation models suggesting that chromosomal rearrangements may have
      contributed to some of the speciation processes along the human and mouse
      lineages. Still, there are other possible causes and further research is needed
      to properly explore them.

PMID- 15951140
TI  - In vitro and in vivo susceptibility of the honeybee bacterial pathogen
      Paenibacillus larvae subsp. larvae to the antibiotic tylosin.
AB  - The minimal inhibitory concentrations (MICs) of tylosin were determined to 67
      strains of Paenibacillus larvae subsp. larvae, the causal agent of American
      Foulbrood (AFB) disease, from different geographical origins. MIC values obtained
      ranged from 0.0078 to 0.5 microg/ml. These very low values imply that no
      resistance to tylosin was found in any isolate of the Foulbrood pathogen. The
      measurement of diseased larvae with AFB-clinical symptoms in three different
      field studies demonstrated that tylosin treatment could be effective in vivo. No
      negative effects in colonies were noted at any dosage rates or forms of
      application. These studies demonstrate that tylosin, as tartrate, can be used to
      treat AFB in honeybee colonies.

PMID- 15951141
TI  - Fluorescent amplified fragment length polymorphism genotyping of human and animal
      Staphylococcus aureus isolates from dairy farms with manual milking.
AB  - Fluorescence amplified fragment length polymorphism (fAFLP) was used to assess
      the genetic relatedness of 40 Staphylococcus aureus strains isolated from human
      and animal skin samples in seven dairy farms with manual milking. S. aureus was
      isolated from 11 out of 30 (36%) human skin samples and from 29 out of 100 (29%)
      teat skin samples from apparently healthy cows. Genomic DNA from each isolate was
      double-digested with EcoRI and MseI and complementary oligonucleotide adaptors
      were ligated to the restriction fragments. Pre-selective and selective
      amplification reactions were performed, the amplified fragments were separated by
      electrophoresis in an ABI377 sequencer and analysed using GeneScan 3.1 and
      Genotyper 2.5. Three single isolates (a-c), a predominant cluster with 35
      isolates (d) and another cluster with two isolates (e) were identified. Both
      clusters d and e included human and animal isolates genetically related, because
      the profiles had 90-100% homology. Since no cluster was comprised uniquely of
      human or animal isolates and given the close genetic relatedness among human and
      animal samples in the farms, the present findings support the hypothesis that
      dairy workers can spread S. aureus through manual milking.

PMID- 15951142
TI  - Impact of ACTH administration on the oviductal sperm reservoir in sows: the local
      endocrine environment and distribution of spermatozoa.
AB  - The objective of the study was to investigate if short-term stress in sows
      (simulated by injections of synthetic adrenocorticotrophic hormone (ACTH)) during
      standing oestrus had a negative effect on the local environment in the utero
      tubal junction (UTJ) and isthmus and the distribution of spermatozoa in these
      segments. Fourteen sows were monitored for ovulation using ultrasonography in two
      consecutive oestruses. The sows were fitted with jugular catheters and, from
      onset of the second oestrus, blood samples were collected every second hour. In
      the 2nd oestrus, seven sows were given ACTH every second hour, from the onset of
      standing oestrus until the sow ovulated (ACTH-group), whereas the other seven
      sows remained as controls (C-group) and were given NaCl solution. The sows were
      artificially inseminated 16-18 h before expected ovulation. Six hours after
      ovulation the sows were anaesthetised, and blood samples were repeatedly taken
      from veins draining the uterus and the UTJ-isthmus, respectively. This oviduct
      was thereafter removed and divided in four adjacent sections consisting of: (i)
      the UTJ, (ii) the first, and (iii) the second isthmus segment prior to (iv), the
      ampullary-isthmic junction (AIJ) and the ampulla. The three first-mentioned
      segments were flushed to retrieve spermatozoa, whereas the last one was flushed
      to collect oocytes/ova. The number of spermatozoa attached to the zona pellucida
      was counted. The concentrations of cortisol in jugular blood of the ACTH-group
      sows during the time of ACTH-injections were significantly higher than of the C
      group sows (p<0.05), as were the levels of progesterone (p<0.001). Progesterone
      and cortisol concentrations measured in the blood samples draining the UTJ
      isthmic region 6 h after ovulation did not significantly differ between the
      groups, but the C-group displayed significantly higher concentrations of
      progesterone in the UTJ-isthmic region compared with the levels measured in
      parallel samples taken of jugular blood (p<0.01). The C-group, but not the ACTH
      group, also displayed a significant elevation in progesterone concentration 6h
      after ovulation compared with the basal levels before ovulation (p<0.01). Numbers
      of retrieved spermatozoa were not significantly different between the C-group and
      the ACTH-group. However, there was a tendency for a larger number of spermatozoa
      among sows in the ACTH-group, especially in the isthmic segment adjacent to the
      AIJ. In conclusion, simulated stress induced by injections of ACTH during
      standing oestrus results in elevated concentrations of progesterone before
      ovulation and may interfere with the rise of progesterone after ovulation.
      However, ACTH-injections appeared to augment transport of spermatozoa through the
      female genital tract of pigs.

PMID- 15951143
TI  - Encapsulation efficiency of water-soluble and insoluble drugs in liposomes
      prepared by the microencapsulation vesicle method.
AB  - The microencapsulation vesicle (MCV) method is a liposome preparation technique
      that reproducibly produces liposomes with homogeneous particle sizes with a high
      encapsulation efficiency. Liposomes encapsulating water-soluble drugs, lipophilic
      drugs and an amphiphilic drug were prepared by the MCV method and the
      encapsulation efficiency of the drugs was examined. Three kinds of egg yolk
      lecithin with different iodine values, i.e., purified egg yolk lecithin (PEL),
      partially hydrogenated purified egg yolk lecithin (R-20) and completely
      hydrogenated purified egg yolk lecithin (R-5), were used for membrane materials
      in order to explore the possible effects of membrane rigidity or surface area on
      the encapsulation efficiency of the drug. Water-soluble 5-fluorouracil showed 12
      15% encapsulation efficiency, which was higher than those reported in the
      literature (less than 10%). With the MCV method, theoretically the initial drug
      containing water phase was always separated from the dispersion medium by the
      lecithin-containing oil phase, which was advantageous to maintaining a higher
      encapsulation efficiency of the water-soluble drug. The encapsulation efficiency
      of lipophilic ibuprofen and flurbiprofen was around 90%. As for ketoprofen and
      liposomes were not formed when using hydrogenated egg yolk lecithin R-5, while
      the encapsulation efficiency using PEL or R-20 was around 80%. Amphiphilic
      amitriptyline hydrochloride resulted in a slightly higher encapsulation
      efficiency when dissolved in the water than the chloroform. Among the three kinds
      of lecithin, the most unsaturated PEL tended to show a higher encapsulation
      efficiency, probably due to differences in the packing geometry of the
      hydrophobic carbon chains in the membrane bilayer. The encapsulation efficiency
      of these drugs strongly correlated to the logP(octanol/water) and also tended to
      correlate to the logP(chloroform/water) for the order of the
      logP(chloroform/water) was almost the same as the order of the
      logP(octanol/water) in the drugs examined. As far as the results of this study,
      the logP(octanol/water) was considered to be a better indicator of the
      encapsulation efficiency of a drug in the MCV method.

PMID- 15951144
TI  - Differences between eccentric and rotary tablet machines in the evaluation of
      powder densification behaviour.
AB  - Differences in the dynamics of powder densification between eccentric and rotary
      machine were pointed out by compressing at different compression pressures
      microcrystalline cellulose, lactose monohydrate and dicalcium phosphate dihydrate
      and recovering the corresponding stress/strain data in both machines equipped to
      monitor punches displacement and compression forces. Heckel plots were then
      obtained from these stress/strain data. Curves obtained in the rotary machine
      possess a narrower zone of linearity for the calculation of P(Y) and D(A). The
      effect of the different compression mechanism of the rotary machine on the shape
      of the Heckel plot is more noticeable in a non-deforming material such as
      dicalcium phosphate. The effect of the longer dwell time of the rotary machine on
      the porosity reduction occurring after the maximum pressure has been reached, is
      more noticeable in a ductile material such as microcrystalline cellulose. Heckel
      parameters obtained in the rotary press are in some cases different from those
      recovered in the eccentric machine because of the longer dwell time, machine
      deflection and punch tilting occurring in the rotary machine, although
      theoretically they could better describe the material densification in a high
      speed production rotary machine.

PMID- 15951145
TI  - In vitro HIV type 1 reverse transcriptase inhibitory activities of Thai medicinal
      plants and Canna indica L. rhizomes.
AB  - Water and 80% ethanol extracts of 20 Thai medicinal plants used to treat AIDS
      were tested for their HIV type 1 reverse transcriptase inhibitory activity. The
      water extracts of Ipomoea carnea subsp. fistulosa (aerial parts), Vitex glabrata
      (branch), Vitex trifolia (aerial part), Vitex negundo (aerial part), Canna indica
      (rhizome), and Justicia gendarussa (aerial part) showed HIV-1 RT inhibition ratio
      (% IR) higher than 90% at a 200 microg/ml concentration. The water extract of
      Canna indica rhizomes (IC(50) 22.56 microg/ml) was selected for further study,
      i.e. for its HIV-1 RT inhibition activity and the purification and
      characterization of the active proteins. Proteins in water extract were
      fractionated by ammonium sulfate precipitation and separated by sodium dodecyl
      sulfate acrylamide gel electrophoresis (SDS-PAGE), yielding two proteins, Cip31
      (31 kDa) and Cip14 (14 kDa) with IC50 of 17.41 and 19.25 microg/ml and
      isoelectric point (pI) of 3.5 and 6.35, respectively. Both proteins showed
      significant HIV-1 RT inhibition.

PMID- 15951146
TI  - Renal artery stenting in solitary functioning kidneys: technical and clinical
      results.
AB  - OBJECTIVE: To evaluate the clinical and technical results of renal artery
      stenting for the treatment of renovascular hypertension and renal failure in
      patients with solitary functioning kidney. MATERIALS AND METHODS: Fifteen
      patients with solitary functioning kidney underwent renal artery stenting and
      were followed up for 12-60 months. Before the procedures, systolic and diastolic
      blood pressures and serum creatinine levels were measured and the number of
      antihypertensive drugs was recorded and followed up after stenting. In case of
      restenosis, either in-stent percutaneous transluminal renal angioplasty or stent
      in-stent placement was performed. RESULTS: Primary technical success rate was
      100%. One lesion was nonostial while 14 were ostial. Primary patency rates were
      100% for 6 months, 92.3% for 12 months, and 69.2% for 24 months. The secondary
      patency rate at 24 months was 100%. The differences between the baseline and
      postprocedural values of systolic blood pressures, diastolic blood pressures and
      the number of antihypertensive drug were statistically significant (P < 0.05),
      except the values of serum creatinine. Hypertension was cured in 1 (6.7%)
      patient, improved in 4 (26.6%) and stabilized in 10 (66.7%) patients. Renal
      function improved in 9 (60%), stabilized in 4 (26.6%), and deteriorated in 2
      (13.4%) patients. Minor complication rate was 13.4% and major complication rate
      was 13.4%. CONCLUSION: Revascularization of renal artery stenosis using stent in
      solitary functioning kidneys is a safe and efficient procedure with high primary
      technical results, low restenosis rates and acceptable complication rates. It has
      an improving and controlling effect on blood pressure and renal functions.

PMID- 15951147
TI  - Development and validation of an HPLC-UV method for the analysis of methoxyamine
      using 4-(diethylamino)benzaldehyde as a derivatizing agent.
AB  - Methoxyamine (MX) is a potential new anti-cancer drug. In this paper, a
      quantitative HPLC-UV method for MX using 4-(diethylamino)benzaldehyde (DEAB) as a
      derivatizing agent has been developed and validated. The studies showed that MX
      reacts with DEAB under acidic conditions to form protonated 4
      (diethylamino)benzaldehyde o-methyloxime (DBMOH+). The equilibrium between DBMOH+
      and its conjugate base 4-(diethylamino)benzaldehyde o-methyloxime (DBMO) is
      affected by both buffer concentration and organic solvent content in the
      solution. The method developed uses a reversed phase C18 column for the
      separation of MX derivatives, an internal standard benzil for method calibration,
      and a UV detector at a wavelength of 310 nm for analyte detection. The MX
      derivatives can be resolved in ca. 20 min. The method has a linear calibration
      range from 0.100 to 10.0 microM with a correlation coefficient of 0.999 for MX
      and a detection limit of 5 pmol with a 50 microl sample size. The intra-assay and
      inter-assay precision expressed in terms of percent relative standard deviation
      were < or =5 and 8%; and the intra-assay and inter-assay accuracy defined as the
      measured value divided by the accepted value multiplied by 100% were 94.2-100 and
      92.6-111%, respectively. This method may be used for the analysis of MX in
      pharmaceutical preparations.

PMID- 15951148
TI  - Separation of naproxen enantiomers by supercritical/subcritical fluid
      chromatography.
AB  - An isocratic supercritical/subcritical fluid chromatography method for the
      separation of naproxen enantiomers on the Kromasil CHI-TBB column was
      investigated. The mobile phase was composed of supercritical CO2 with 2-propanol
      as modifier. The experimental conditions were temperature 293 K-323 K, pressure
      9.4 MPa-21.3 MPa, and 2-propanol concentration 6%-15% (by mass), respectively.
      The enthalpic contribution to the overall enantiomer transfer energy was more
      important than the entropic contribution in the temperature range examined. The
      preferred operation conditions were 293 K, 9.4 MPa, and the concentration of 2
      propanol in the mobile phase 11% (by mass).

PMID- 15951149
TI  - Development and validation of a sensitive GC-MS method for the determination of
      trace levels of an alkylating reagent in a beta-lactam active pharmaceutical
      ingredient.
AB  - A direct injection gas chromatographic method utilizing selected-ion monitoring
      (SIM) mode mass selective detection was developed and validated for the trace
      analysis of an impurity, carbonic acid chloromethyl tetrahydro-pyran-4-yl ester
      (CCMTHP), present in a beta-lactam active pharmaceutical ingredient (API). A
      variety of analytical techniques including LC-MS, GC-FID, GC-ECD and GC-MS were
      evaluated during the method development. GC-MS with SIM at m/z=49 demonstrated
      the best detection sensitivity. A 10 ppm (5 pg on column) limit of quantitation
      (LOQ) was attained and the linearity of the method was demonstrated in the range
      of 10-1000 ppm. Accurate and precise quantitation of the impurity in drug
      substance was achieved with external standardization. A 10:1 split injection was
      applied to limit the amount of non-volatile API loading onto the column. The
      effects of injection and detection parameters such as split ratio, liner type,
      injection temperature and number of mass ions monitored were studied. Full
      validation proved the accuracy, precision and specificity of the method, which
      was successfully employed to analyze many pilot lots of the API.

PMID- 15951150
TI  - Bio-chemotherapeutic strategies and the (dis) utility of hypoxic perfusion of
      liver, abdomen and pelvis using balloon catheter techniques.
AB  - AIMS: To review the development and current status of balloon catheter mediated
      hypoxic perfusion of abdomen, pelvis and liver for treatment of locally advanced
      malignancies. Within this context we focus on the addition of tumour necrosis
      factor-alpha (TNF) to these minimal invasive perfusion procedures. METHODS: A
      literature search on these topics was carried out in PubMed for indexed articles
      and in all issues of Regional Cancer Treatment. The findings were related to our
      own experiences. RESULTS: Hypoxic abdominal (HAP) and hypoxic pelvic perfusion
      (HPP) using balloon catheters, are currently applied modalities for treatment of
      a wide variety of abdominal and pelvic tumours, yet scientific validation of
      these procedures is poor. Following the results of several Phase I-II trials,
      both treatments are associated with severe systemic toxicity, significant
      morbidity and even mortality. The degree of systemic leakage associated with
      these procedures prohibits addition of TNF. For leakage free liver perfusion
      surgery is still required, as with current balloon catheter techniques it is not
      possible to perform leakage free isolated hypoxic hepatic perfusion (IHHP), using
      either orthograde or retrograde hepatic flow. Experimental and clinical
      observations suggest that within any perfusion setting, the utilization of TNF is
      only indicated for treatment of highly vascularised tumours and not for treatment
      of colorectal tumours. CONCLUSION: Balloon catheter technology in its present
      form does not provide adequate leakage control in any of these settings and is
      therefore associated with considerable toxicity. It is associated with poor
      response rates and cannot be considered in any setting as a standard of care.

PMID- 15951151
TI  - Re: Sakorafas GH, Geraghty J, Pavlakis G. The clinical significance of axillary
      lymph node micrometastases in breast cancer. Eur J Surg Oncol 2004;30(8):807-16.

PMID- 15951152
TI  - Different roles of Fpg and Endo III on catechol-induced DNA damage in extended
      term cultures of human lymphocytes and L5178Y mouse lymphoma cells.
AB  - Catechol is a genotoxic agent assumed to induce DNA damage via the oxidative
      pathway. Using the comet assay and the repair-specific enzymes formamido
      pyrimidine glycosylase (Fpg) and endonuclease III (Endo III), we examined the
      ability of catechol to induce DNA damage in extended-term cultures of human
      lymphocytes and mouse lymphoma cells. Our results suggest that mouse lymphoma
      cells are somewhat more sensitive towards catechol-induced DNA damage than the
      extended-term cultures of human lymphocytes. At high concentrations, the catechol
      induced damage seemed to be independent of both Fpg and Endo III, possibly
      indicating a non-oxidative pathway for the DNA damage (involving, for example, a
      bulky adduct). The fact that Endo III, but not Fpg, enhanced the DNA damaging
      effect of catechol, suggests that this metabolite of benzene either mediates
      oxidation of pyrimidines rather than purines, or that oxidised purines are
      repaired more efficiently, at least in human lymphocytes. In the latter cells,
      low concentrations of catechol were found to reduce the DNA migration.
      Considering the role of Fpg and it's adduct specific detection of 8-oxoguanine,
      this suggests that a low concentration of catechol has an antioxidative effect
      reducing the background levels of oxidized purines.

PMID- 15951153
TI  - Assessing olfaction in the neuropsychological exam: the relationship between odor
      identification and cognition in older adults.
AB  - The relationship between odor identification and cognition has not been
      previously well characterized. The neuroanatomy of the olfactory system and the
      frequent finding of olfactory dysfunction in neurodegenerative diseases suggest a
      likely relationship between odor identification and memory, language, and
      executive functioning, though previous studies have often failed to demonstrate
      the expected relationship. The current study examined this relationship in across
      a continuum of ability levels (N=100). Strongest correlations were found between
      odor identification and language, most aspects of memory, and a measure of
      general cognitive functioning. Significant but more modest correlations were seen
      between odor identification and attention, motor, visuospatial, and executive
      functions. A regression analysis revealed language as the only significant
      predictor of olfactory performance. These findings suggest that odor
      identification is most closely associated with other measures of temporo-limbic
      functioning. The implications of these findings, particularly in consideration of
      the assessment of older adults, are discussed.

PMID- 15951154
TI  - Synchronous global assessment of gene and protein expression in colorectal cancer
      progression.
AB  - Well-established models of colorectal cancer progression are based on the idea
      that the disease evolves through a multistep process involving sequential genetic
      mutations, suggesting that progression through clinically defined stages should
      correlate with well-defined patterns of gene expression. The majority of studies
      to date, however, have assessed these processes one gene and one protein at a
      time. We report the first comprehensive assessment of both gene and protein
      expression performed in parallel across progressive stages of human colorectal
      neoplasia. Remarkably, despite the global nature of the gene expression
      assessment, very few genes could be linked with certainty to specific proteins
      through currently available annotations. Furthermore, the correlation of
      expression between identified genes and proteins was poor. Nevertheless, both
      produced expression signatures that differentiated normal mucosa and nonmalignant
      adenomas from each other and from the malignant carcinomas and both produced
      fairly consistent subclasses of the malignancies, suggesting that a molecular
      staging might be more appropriate provided that these profiles can be tied to
      clinical outcome. This is potentially important as clinical staging is widely
      used as a prognostic indicator and used in the decision to pursue adjuvant
      therapies.

PMID- 15951155
TI  - Influenza virus-induced glucocorticoid and hypothalamic and lung cytokine mRNA
      responses in dwarf lit/lit mice.
AB  - Influenza virus infection up-regulates cytokines such as interleukin-1beta (IL
      1beta) and activates the somatotropic axis and the hypothalamic-pituitary axis.
      Mice with deficits in growth hormone releasing hormone (GHRH) signaling (lit/lit
      mice) respond to influenza virus challenge with a progressive decrease in sleep
      and lower survival rates. Current experiments characterize plasma glucocorticoid
      responses and hypothalamic and lung mRNA expression of sleep-related genes in
      lit/lit mice and their heterozygous controls after influenza virus challenge.
      lit/lit mice had higher basal and post-infection plasma corticosterone levels
      compared to controls. In contrast, the heterozygous mice increased hypothalamic
      GHRH-receptor, CRH-type 2 receptor, IL-1beta, and tumor necrosis factor-alpha
      (TNF-alpha) mRNAs after virus treatment while the lit/lit mice failed to up
      regulate these substances. In contrast, lung levels of IL-1beta and TNF-alpha
      mRNAs were greater in the lit/lit mice. These data are consistent with the
      hypothesis that the sleep response to influenza infection is mediated, in part,
      by an up-regulation of hypothalamic sleep-related transcripts and they also show
      that a primary deficit in GHRH signaling is associated with enhanced
      corticosterone secretion and attenuated hypothalamic cytokine response to
      infection.

PMID- 15951156
TI  - Valine-286 residue in the third intracellular loop of the cholecystokinin 2
      receptor exerts a pivotal role in cholecystokinin 2 receptor mediated
      intracellular signal transduction in human colon cancer cells.
AB  - Although expression of the gastrin/cholecystokinin-2 receptor (CCK2R) is widely
      reported in human colorectal cancer, little is known on its role in mediating
      mature amidated gastrin (gastrin-17 amide, G-17) induced intracellular signal
      transduction in colon cancer cells. The purpose of this study was to explore the
      intracellular events of colorectal cancer cells after gastrin binding to CCK2R.
      Meanwhile, the influence of a natural point mutation 286V-->F in the third
      intracellular loop of CCK2R on gastrin-envoked intracellular signal transduction
      was also investigated. Firstly, Colo320 cells were stably transfected with wild
      type (Colo320 WT) and mutant CCK2R (Colo320 M), respectively. The intracellular
      signal transduction events in response to gastrin were investigated in both
      Colo320 WT and Colo320 M cells. In Colo320 WT cells, G-17 induced formation of
      intracellular cyclic AMP and inositol 1,4,5-trisphosphate, and stimulated
      intracellular calcium mobilization. G-17 also stimulated tyrosine phosphorylation
      of ERKl/2, p38, FAK, and paxillin, and up-regulated the mRNA expression of early
      response gene c-Jun and c-Fos. However, G-17 inhibited proliferation and induced
      apoptosis in Colo320 WT cells. Mutation 286V-->F in the third intracellular loop
      of CCK2R blocked G-17 induced biological without affecting binding affinity of
      CCK2R to G-17. Our results suggest that activation of CCK2R by gastrin stimulates
      heterotrimeric G-protein Gq and G(12/13) mediated intracellular signal
      transduction pathway in colon cancer cells. The valine-287 residue in third
      intracellular loop of CCK2R plays a pivotal role in CCK2R mediated intracellular
      signal transduction.

PMID- 15951157
TI  - Ciglitazone-induced p27 gene transcriptional activity is mediated through Sp1 and
      is negatively regulated by the MAPK signaling pathway.
AB  - We have previously demonstrated that the PPARgamma ligand, ciglitazone, increases
      p27kip1 protein levels in HT-29 colon cancer cells through both inhibition of
      proteasome associated degradation and activation of transcriptional activity. [F.
      Chen, L.E. Harrison, Cell Signal. 17 (2005) 809] The purpose of this
      investigation was to further elucidate the mechanism of ciglitazone-induced
      activation of p27 gene transcription. We observed that the region -774/-462 of
      the p27 promoter plays a key role in ciglitazone-induced gene transcriptional
      activity and this region contains two Sp1 binding sites. When the p27PF-luc
      reporter was co-transfected with Sp1 expression plasmids, ciglitazone-induced
      p27PF-luc activity significantly increased, while mithramycin A, a Sp1 inhibitor,
      was able to abrogate its effects. Ciglitazone exposure increased both Sp1 protein
      expression and Sp1-DNA binding, which was also associated with a decrease of
      Erk1/2 phosphorylation. A similar increase of Sp1-DNA binding was observed when
      phosphorylation of Erk1/2 was inhibited by pretreatment with the MAP kinase
      inhibitor, U0126. In addition, a significant increase of p27PF-luc reporter
      luciferase activity was noted after MAP kinase inhibition, which could be
      abolished with co-treatment with mithramycin A. Based on these data, we postulate
      that ciglitazone induces p27 gene transcription through increased Sp1 binding to
      its promoter region, which in turn is mediated through increased Sp1 protein
      levels and decreased inhibitory regulation by the MAP kinase pathway.

PMID- 15951158
TI  - Identification of interaction sites of protein kinase Calpha on phospholipase D1.
AB  - Phospholipase D (PLD) is regulated by many factors, including protein kinase C
      (PKC) and small G-proteins of the Rho and ADP-ribosylation factor families.
      Previous studies revealed that the activation of PLD1 by phorbol ester is
      associated with the binding of PKCalpha to a site in the N-terminus of PLD1. The
      purpose of the present study was to determine this site more precisely.
      Immunoprecipitation with a series of four PLD1 deletion mutants confirmed that
      PKCalpha strongly interacted with the amino acid sequence 1-318 at the N-terminus
      of PLD1 and weakly with the sequence 841-1036 at the C-terminus. Further
      immunoprecipitation studies with deletion mutants of the 1-318 and 1-215 PLD1
      fragments revealed that there were binding sites in the 1-49 N-terminal sequence
      and also in the 216-318 sequence containing the PH domain. Studies of N-terminal
      deletion mutants of full-length PLD1 confirmed the presence of a binding site in
      the 1-49 sequence and a further site in the 1-318 sequence. Both deletion mutants
      showed impaired activation by PKCalpha in vivo, but unchanged activation by
      active V(14)RhoA. These findings identify the 1-49 sequence is a major
      binding/activation site for PKCalpha on PLD1, but also indicate involvement of
      the PH domain.

PMID- 15951159
TI  - Antimicrobial activity and a comparison of published pharmacodynamics of
      gemifloxacin and eight fluoroquinolones against Streptococcus pneumoniae.
AB  - Gemifloxacin was evaluated for its in vitro activity and was compared with eight
      fluoroquinolones. Pharmacodynamic comparisons were made based on published
      pharmacokinetic information. Gemifloxacin demonstrated excellent in vitro
      activity (minimum inhibitory concentration necessary to inhibit 90% of the
      strains tested, MIC90 = 0.03 mg/L (range 0.0019-0.03 mg/L)) against 199 strains
      of Streptococcus pneumoniae. Its activity was not influenced by penicillin or
      ciprofloxacin non-susceptibility. Gemifloxacin demonstrated excellent
      pharmacodynamic parameters, with a Cmax/MIC90 of 67 (where Cmax is the peak serum
      level) and an AUC/MIC90 of 297 (where AUC is the area under the curve). Compared
      with the other eight fluoroquinolones tested, gemifloxacin demonstrated the best
      in vitro activity and Cmax/MIC90.

PMID- 15951160
TI  - The epidemiology of generalized anxiety disorder in Europe.
AB  - The objective of this paper is to provide a review on available data to date on
      the epidemiology of GAD in Europe, and to highlight areas for future research.
      MEDLINE searches were performed and supplemented by consultations with experts
      across Europe to identify non-published reports. Despite variations in the design
      of studies, available data suggest that (a) about 2% of the adult population in
      the community is affected (12-month prevalence), (b) GAD is one of the most
      frequent (up to 10%) of all mental disorders seen in primary care, (c) GAD is a
      highly impairing condition often comorbid with other mental disorders, (d) GAD
      patients are high utilizers of healthcare resources, and (e) despite the high
      prevalence of GAD in primary care, its recognition in general practice is
      relatively low. Marked data deficits are: lack of data from eastern European
      countries, lack of information about the natural course of GAD in unselected
      samples, the vulnerability and risk factors involved in the aetiology of GAD and
      lack of data about adequate and inappropriate treatments in GAD patients as well
      as the associated and societal costs of GAD.

PMID- 15951161
TI  - Reduced stress pattern discrimination in 5-month-olds as a marker of risk for
      later language impairment: neurophysiologial evidence.
AB  - The study at hand investigates prosodic abilities of infants as early predictors
      of Specific Language Impairment (SLI), which is commonly diagnosed at a later
      age. The study is based on the hypothesis that the prosodic abilities of infants
      at risk for SLI are less elaborated than those of controls due to less efficient
      processing of the relevant acoustic cues. One of the most critical prosodic cues
      for word segmentation is stress pattern. In German as well as in English, the
      most frequent stress pattern of bisyllabics is the trochee, in which stress is
      placed on the first syllable. Using a passive oddball design, German 5-month-olds
      were examined with respect to their ability to discriminate different stress
      patterns of bisyllabics. Infants were grouped retrospectively based on their
      production performance at the ages of 12 and 24 months. In contrast to matched
      controls, infants with very low word production displayed event-related brain
      potentials with a significantly reduced amplitude of the discrimination response,
      i.e. a Mismatch Negativity (MMN), to the trochaic stress pattern. This amplitude
      difference indicates impaired prosodic processing of word stress during early
      development and may thus be taken as an early marker of risk for SLI.

PMID- 15951162
TI  - High-dose lidocaine reduces airway mucus transport velocity in intubated
      anesthetized dogs.
AB  - BACKGROUND: Assessment of mucociliary clearance with displacement of charcoal
      markers in the central airways needs a bronchoscopic procedure and thus local
      anesthesia of the upper airways. However, the effects of lidocaine administration
      on mucus transport in airways are inconclusive. Therefore, detailed information
      is needed to establish the effects of high- and low-dose lidocaine
      administration. OBJECTIVES: To study the dose-dependent effect of instillation of
      lidocaine on mucus transport velocity (MTV) in intubated, anaesthetized dogs.
      METHODS: Displacement of a charcoal spot in time was studied with a bronchoscope
      in 10 anaesthetized dogs before and after administration of respectively 5 and 10
      ml of either 2% lidocaine (n=5) or NaCl 0.9% (n=5). In addition, mucus
      viscoelastic properties were determined. RESULTS: No significant differences in
      MTV were observed after administration of 5 ml of NaCl (8.2+/-3.2 mm/min) or 2%
      lidocaine (6.7+/-3.8 mm/min) compared to baseline values. By contrast, MTV was
      reduced after administration of 10 ml of 2% lidocaine (1.9+/-1.0 mm/min; P<0.05
      vs. baseline and 5 ml of 2% lidocaine vs. controls, P=0.0035), but not after 10
      ml of NaCl (6.2+/-2.1 mm/min). A trend towards an increased mucociliary
      clearability index was observed for the lidocaine-treated group as compared to
      the control group (P=0.07). The cough clearability index was not different
      between groups (P=0.89). CONCLUSIONS: High-dose lidocaine reduces MTV. Therefore,
      only low-dose lidocaine administration should be applied in the bronchoscopic
      procedure for assessment of MTV.

PMID- 15951163
TI  - A nanoparticle amplification based quartz crystal microbalance DNA sensor for
      detection of Escherichia coli O157:H7.
AB  - A quartz crystal microbalance (QCM) DNA sensor, based on the nanoparticle
      amplification method, was developed for detection of Escherichia coli O157:H7. A
      thiolated single-stranded DNA (ssDNA) probe specific to E. coli O157:H7 eaeA gene
      was immobilized onto the QCM sensor surface through self-assembly. The
      hybridization was induced by exposing the ssDNA probe to the complementary target
      DNA, and resulted in the mass change and therefore frequency change of the QCM.
      Streptavidin conjugated Fe(3)O(4) nanoparticles (average diameter=145 nm) were
      used as "mass enhancers" to amplify the frequency change. Synthesized
      biotinylated oligonucleotides as well as E. coli O157:H7 eaeA gene fragments (151
      bases) amplified using asymmetric PCR with biotin labeled primers were tested. As
      low as 10(-12)M synthesized oligonucleotides and 2.67 x 10(2) colony forming unit
      (CFU)/ml E. coli O157:H7 cells can be detected by the sensor. Linear correlation
      between frequency change and logarithmic number of bacterial cell concentration
      was found for E. coli O157:H7 from 2.67 x 10(2) to 2.67 x 10(6)CFU/ml.

PMID- 15951164
TI  - Tuberin and hamartin are aberrantly expressed and linked to clinical outcome in
      human breast cancer: the role of promoter methylation of TSC genes.
AB  - PURPOSE: The tuberous sclerosis (TSC) genes TSC1 and TSC2 encode the protein
      products hamartin and tuberin, respectively, and are putative tumour suppressor
      genes. Germ-line mutation of either TSC gene leads to the development of the
      heritable disorder TSC. This disorder is characterized by the development of
      hamartomas in many organs and is associated with the proliferative lung disease,
      lymphangioleiomyomatosis, the brain tumour giant cell astrocytoma and
      occasionally with renal cell carcinoma. However, the TSC genes have not been
      studied in breast cancer. The current study investigated the expression of the
      TSC gene products and the potential mechanisms of their aberrancy in human breast
      cancer cells and tissues. EXPERIMENTAL DESIGN AND RESULTS: Using
      immunohistochemical analysis, both hamartin and tuberin were found to be strongly
      stained in normal mammary epithelial cells and weakly in stromal cells. In
      invasive tumour tissues, however, the staining of both proteins were to be
      markedly reduced (P < 0.01). At message level, although normal and tumour tissues
      expressed both TSC products, the transcript levels of tuberin was significantly
      lower in tumour tissues compared with normal tissues (P < 0.05). There was no
      statistical difference between node negative and node positive tumours with both
      hamartin and tuberin. Tumours from patients who developed recurrence and died
      from breast cancer had significantly low levels of tuberin compared with those
      who remained disease free (P = 0.03 and 0.05, respectively). Likewise, hamartin
      levels were significantly lower in patients with metastasis, recurrence and
      mortality, when compared with those remained disease free (P = 0.001, 0.041 and
      0.003, respectively). Using methylation specific PCR, the TSC1 promoter was found
      to be heavily methylated in ZR751, MDA MB 435, and BT549, but not in MCF-7 which
      expressed highly level of hamartin. TSC1 promoter methylation was also seen in
      most breast tumours, but only in a limited number of normal tissues. The
      methylation of TSC2 promoter appears to be less frequent. MDA MB 468, MDA MB 483,
      MDA MB 435S and weakly MDA MB 435 were found to have methylated TSC2 promoter. In
      breast tissues, however, a very small number of samples were found to have
      methylation of the TSC2 promoter. CONCLUSION: TSC1 genes are aberrantly expressed
      in human breast cancer cell lines and breast tumour tissues and their promoters
      are seen to be methylated in breast tumour tissues. The expression of TSC1 is
      associated with an unfavourable clinical outcome in patients with breast cancer.

PMID- 15951165
TI  - Cisplatin plus vinorelbine or gemcitabine in patients with advanced non-small
      cell lung cancer: pharmacoeconomic considerations.

PMID- 15951166
TI  - Production of exopolysaccharides by submerged culture of an enthomopathogenic
      fungus, Paecilomyces tenuipes C240 in stirred-tank and airlift reactors.
AB  - The objective of this study was to investigate the effect of shearing effect on
      the production of exopolysaccharides (EPS) from an enthomopathogenic fungus,
      Paecilomyces tenuipes C240 in a stirred-tank reactor (STR) and in an airlift
      reactor (AR). The optimal agitation rate for the production of EPS in the STR was
      150 rpm with the mycelial morphology of hairy pellets, where the final
      concentration and the specific production rate of EPS were 2.33 g l(-1) and 0.312
      gg(-1) h(-1), respectively. However, the maximum concentration of biomass (21.06
      g l(-1)) in the STR was obtained at a high agitation speed of 300 rpm. The
      specific production rate of EPS (0.456 gg(-1) h(-1)) in the AR was significantly
      higher than that achieved in the STR, in which the typical morphological form of
      mycelium was a loose clump. The three EPS groups in the STR (designated as STR-I,
      -II, and -III) and two groups of EPS in the AR (designated as AR-I and -II) were
      obtained from the culture filtrates by a gel filtration chromatography on
      Sepharose CL-6B. The molecular weights of STR-I, STR-II, STR-III, AR-I, and AR-II
      were determined to be 1,820, 25, 1.8, 1,160, and 6.7 kDa, respectively. An
      agitation rate of 150 rpm in the STR was selected as the optimal culture
      condition for maximum EPS production (2.33 g l(-1)), which was similar to the
      level achieved in the AR (2.30 g l(-1)). The carbohydrate composition in each EPS
      was quite different from each other: the major component was glucose (in STR-I, 
      III, and AR-I), mannose (in STR-II), and arabinose (in AR-II). In contrast, no
      significant difference in amino acid composition was observed.

PMID- 15951167
TI  - Functional characteristics of shrimp chitosan and its membranes as affected by
      the degree of deacetylation.
AB  - The functional properties of three shrimp chitosan preparations with different
      degrees of deacetylation (75%, 87% and 96% DD) but with a constant molecular
      weight (about 810 kDa) were investigated. Chitosan with 75% DD had a 1.5 times
      higher water absorption, probably due to its 20% lower level of crystallinity.
      Membranes cast from this chitosan also exhibited 1.5 times more water absorption
      and 2 times higher permeability. However, chitosan with 87% and 96% DD had 1.5-2
      times higher absorption of fat and the orange II dye. This is attributed to the
      higher content of positively charged amine groups in the polymer. Cast into
      membrane, chitosan of higher degree of deacetylation showed a higher tensile
      strength and a higher elongation at break, probably due to the higher level of
      crystallinity.

PMID- 15951168
TI  - Isolation and characterization of biosurfactant/bioemulsifier-producing bacteria
      from petroleum contaminated sites.
AB  - Biosurfactant-producing bacteria were isolated from terrestrial and marine
      samples collected in areas contaminated with crude oil or its byproducts.
      Isolates were screened for biosurfactant/bioemulsifier production in different
      carbon sources (glucose, fructose, sucrose and kerosene) using the qualitative
      drop-collapse test. Glucose produced the highest number of positive results (17
      of 185 isolates). All 17 isolates produced emulsions with kerosene and 12
      exhibited high emulsion-stabilizing capacity, maintaining 50% of the original
      emulsion volume for 48 h. Eight of the 17 isolates reduced the growth medium
      surface tension below 40 mN m(-1) with 5 exhibiting this capacity in cell-free
      filtrates. Onset of biosurfactant production differed among the isolates, with
      some initiating synthesis during the exponential growth phase and others after
      the stationary phase was reached. Increasing temperature from 25 to 35 degrees C
      accelerated onset of biosurfactant production in only two isolates while pH (6.5
      7.6) had no effect in any isolate tested. Isolation from petroleum contaminated
      sites using the screening protocol presented proved to be a rapid and effective
      manner to identify bacterial isolates with potential industrial applications.

PMID- 15951169
TI  - Cloning, sequencing and expression of the xylanase gene from a Bacillus subtilis
      strain B10 in Escherichia coli.
AB  - Bacillus subtilis strain B10 was isolated for degumming of ramie blast fibers,
      and a fragment of 642-bp was amplified from chromosomal DNA by using primers
      directed against the sequence of Bacillus subtilis xylanase gene given in
      GenBank. The positive clones were screened on the selected LB agar plates
      supplemented with xylan by Congo-red staining method. The recombinant plasmid
      from one positive clone was used for further analysis and DNA sequencing. The
      gene sequence is different from the reported xylanase gene sequence in sites of
      two base pairs. The recombinant plasmid was expressed in Escherichia coli, and
      xylanase activity was measured. The xylanase distribution in extracellular,
      intracellular and periplasmic fractions were about 22.4%, 28.0% and 49.6%,
      respectively. The xylanase had optimal activity at pH 6.0 and 50 degrees C.

PMID- 15951170
TI  - Isomeric thiazole derivatives as ligands for the neuropeptide Y5 receptor.
AB  - Sets of isomeric thiazole derivatives 1 and 2 have been synthesised in a parallel
      iterative solution-phase synthesis approach guided by the SAR analysis derived
      from biological results and computer-aided design and analysis. This synergistic
      and streamlined working procedure led to highly active isomeric NPY5 receptor
      ligands. However, a 10-fold difference at least in their respective binding
      affinities was consistently found for all isomeric pairs 1 and 2. The analysis of
      conformational differences due to heteroatom interactions in 1 and 2 revealed a
      favourable C=O...S interaction in 1, whereas thiazoles 2 showed a repulsive
      C=O...N interaction.

PMID- 15951171
TI  - Structure-activity relationships of 1,3,5-triazine-2,4,6-triones as human
      gonadotropin-releasing hormone receptor antagonists.
AB  - SAR studies of 1,3,5-triazine-2,4,6-triones as human gonadotropin-releasing
      hormone receptor antagonists resulted in potent compounds. The best compound from
      the series had a binding affinity of 2 nM.

PMID- 15951172
TI  - Synthesis of functionalized acetophenones as protein tyrosine phosphatase 1B
      inhibitors.
AB  - Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that plays a critical role
      in down-regulating insulin signaling through dephosphorylation of the insulin
      receptor. Studies have shown that PTP1B knock-out mice showed increased insulin
      sensitivity in muscle and liver as well as resistance to obesity. A series of
      functionalized acetophenones were synthesized and evaluated for their PTP1B
      inhibitory activity. Some of the screened compounds displayed good inhibitory
      activity.

PMID- 15951173
TI  - An improved synthesis of 5'-fluoro-5'-deoxyadenosines.
AB  - Synthesis of 5'-fluoro-5'-deoxyadenosine (5'-FDA) and structurally similar
      compounds is generally a poor yielding process. This is attributed to the
      instability of the selected synthetic intermediates. Herein, we report a general
      synthesis of 5'-fluoro-5'-deoxy-N6-substituted adenosines including a high
      yielding access to 5'-FDA.

PMID- 15951174
TI  - Synthesis of cationic beta-vinyl substituted meso-tetraphenylporphyrins and their
      in vitro activity against herpes simplex virus type 1.
AB  - An easy route to cationic beta-vinyl substituted meso-tetraphenylporphyrin
      derivatives is described. Two novel compounds were tested in vitro for their
      antiviral photoactivity against herpes simplex virus type 1. One of these
      compounds exhibited a significant activity, reaching 99% of virus inactivation
      after 15 min of photoactivation.

PMID- 15951175
TI  - 1-Amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid as a Tic mimetic:
      application in the synthesis of potent human melanocortin-4 receptor selective
      agonists.
AB  - The discovery of 1-amino-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid analogs
      as potent human melanocortin-4 selective agonists is described.

PMID- 15951176
TI  - Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as
      inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
AB  - 2'-Deoxy, 3'-deoxy, and 2',3'-dideoxyribosyl surrogates of isoleucyl and
      methionyl sulfamate adenylates have been investigated to identify the
      pharmacophoric importance of the ribose group for the inhibition of Escherichia
      coli methionyl-tRNA (MRS) and isoleucyl-tRNA (IRS) synthetases. Molecular
      modeling of 2',3'-dideoxyribosyl Met-NHSO2-AMP (9) with the crystal structure of
      E. coli MRS revealed that the lack of the two hydroxyl groups on ribose was
      compensated by the formation of an extra hydrogen bond between the ring oxygen
      and His24, resulting in a small activity reduction.

PMID- 15951177
TI  - 126th International Workshop: congenital myasthenic syndromes, 24-26 September
      2004, Naarden, the Netherlands.

PMID- 15951178
TI  - p27(Kip1) and stathmin share the stage for the first time.
AB  - Cell migration is essential for development, morphogenesis, tissue repair and
      tumor metastasis. p27(Kip1) and stathmin are two cell-cycle-regulatory proteins
      that were recently shown to play important roles in the regulation of cell
      migration. In this article, we discuss a new study that places p27(Kip1) and
      stathmin in the same pathway by showing that stathmin, a microtubule-regulatory
      protein, mediates the effects of p27(Kip1) on cell motility. These findings
      provide new insights into migration and metastasis of tumor cells and the
      relationship of these processes to cell proliferation.

PMID- 15951179
TI  - Modulation of lung epithelial functions by Pseudomonas aeruginosa.
AB  - Microorganisms gain access to the airways and respiratory epithelial surface
      during normal breathing. Most inhaled microbes are trapped on the mucous layer
      coating the nasal epithelium and upper respiratory tract, and are cleared by
      ciliary motion. Microorganisms reaching the alveolar spaces are deposited on the
      pulmonary epithelium. This contact initiates complex offensive and defensive
      strategies by both parties. Here, we briefly outline how the pulmonary pathogen
      Pseudomonas aeruginosa uses multi-pronged strategies that include cell surface
      appendages, and secreted and injected virulence determinants to switch from an
      unobtrusive soil bacterium to a pathogen for lung epithelium colonization.
      Understanding the complex interactions between the lung epithelium and P.
      aeruginosa might enable more effective therapeutic strategies against infection
      in cystic fibrosis and immuno-compromised individuals.

PMID- 15951180
TI  - Bridging gaps in phospholipid transport.
AB  - Phospholipid transport between membranes is a fundamental aspect of organelle
      biogenesis in eukaryotes; however, little is know about this process. A
      significant body of data demonstrates that newly synthesized phospholipids can
      move between membranes by routes that are independent of the vesicular traffic
      that carries membrane proteins. Evidence continues to accumulate in support of a
      system for phospholipid transport that occurs at zones of apposition and contact
      between donor membranes - the source of specific phospholipids - and acceptor
      membranes that are unable to synthesize the necessary lipids. Recent findings
      identify some of the lipids and proteins that must be present on membranes for
      inter-organelle phospholipid transport to occur between the endoplasmic reticulum
      and mitochondria or Golgi. These data suggest that protein and lipid assemblies
      on donors and acceptors promote membrane docking and facilitate lipid movement.

PMID- 15951181
TI  - CIF and other mysteries of the store-operated Ca2+-entry pathway.
AB  - The molecular mechanism of the store-operated Ca2+-entry (SOCE) pathway remains
      one of the most intriguing and long lasting mysteries of Ca2+ signaling. The
      elusive calcium influx factor (CIF) that is produced upon depletion of Ca2+
      stores has attracted growing attention, triggered by new discoveries that filled
      the gap in the chain of reactions leading to activation of store-operated
      channels and Ca2+ entry. Ca2+-independent phospholipase A2 emerged as a target of
      CIF, and a major determinant of the SOCE mechanism. Here, we present our
      viewpoint on CIF and conformational-coupling models of SOCE from a historical
      perspective, trying to resolve some of the problem areas, and summarizing our
      present knowledge on how depletion of intracellular Ca2+ stores signals to plasma
      membrane channels to open and provide Ca2+ influx that is required for many
      important physiological functions.

PMID- 15951182
TI  - Dimer-based model for heptaspanning membrane receptors.
AB  - The existence of intramembrane receptor-receptor interactions for heptaspanning
      membrane receptors is now fully accepted, but a model considering dimers as the
      basic unit that binds to two ligand molecules is lacking. Here, we propose a two
      state-dimer model in which the ligand-induced conformational changes from one
      component of the dimer are communicated to the other. Our model predicts
      cooperativity in binding, which is relevant because the other current models fail
      to address this phenomenon satisfactorily. Our two-state-dimer model also
      predicts the variety of responses elicited by full or partial agonists, neutral
      antagonists and inverse agonists. This model can aid our understanding of the
      operation of heptaspanning receptors and receptor channels, and, potentially, be
      important for improving the treatment of cardiovascular, neurological and
      neuropsychyatric diseases.

PMID- 15951183
TI  - An approach toward the problem of outliers in QSAR.
AB  - Compounds that have unexpected biological activity and are unable to fit in a
      QSAR model are known as outliers. These are valuable in defining the limitations
      under which compounds act by a common molecular mechanism modeled by one or more
      descriptors, and also in defining the experimental limitations of the biological
      test data. Thus, the outliers should be submitted to particular attention to see
      if the reason for their peculiarity can be determined. Separating these outliers
      from the main data set and formulating another QSAR can resolve the problem. Our
      result shows that these outliers may be acting by a different mechanism or
      interacting with the receptor in different modes.

PMID- 15951184
TI  - Novel cytotoxic monotetrahydrofuranic Annonaceous acetogenins from Annona
      montana.
AB  - Four new monotetrahydrofuranic Annonaceous acetogenins, montalicins G (1) and H
      (2) and monlicins A (3) and B (4), and two new linear acetogenins, (+)-monhexocin
      (5) and (-)-monhexocin (6), as well as three known compounds, murisolin (7), 4
      deoxyannomontacin (8), and muricatacin (9), were isolated from the seeds of
      Annona montana by high performance liquid chromatographic (HPLC) method. The
      absolute stereochemical structures of new isolates were elucidated and
      characterized by spectral and chemical methods. Interestingly, these compounds
      show special cytotoxicity against human hepatoma cells, Hep G2.

PMID- 15951185
TI  - Optically active cantharidin analogues possessing selective inhibitory activity
      on Ser/Thr protein phosphatase 2B (calcineurin): implications for the binding
      mode.
AB  - Cantharidin is well known as a potent serine/threonine protein phosphatase 1 and
      2A (PP1 and PP2A) inhibitor, with less potent inhibitory activity for PP2B, which
      regulates T-cell proliferation. We synthesized and evaluated four optically pure
      stereoisomers of 1-substituted norcantharidin analogues. The absolute
      stereochemistry of each stereoisomer was determined based on X-ray crystal
      structure analysis. Remarkably, optically active cantharidin analogues having
      (1S)-configuration showed selective inhibition of PP2B, without inhibiting PP1 or
      PP2A.

PMID- 15951186
TI  - 1,12-substituted tetracyclines as antioxidant agents.
AB  - Novel hydroxypyrazoline derivatives of tetracycline and minocycline have been
      synthesized through the reaction of these tetracyclines with hydrazine. The
      formation of a new chiral center at C12 is stereospecific to give 12S-12-hydroxy
      1,12-pyrazolinotetracycline. A reaction mechanism for the formation of these
      novel tetracycline derivatives has been proposed. Hydroxypyrazolinotetracyclines
      exhibit no binding to Mg2+ and Zn2+, features that are required for antibiotic
      activity and matrix metalloproteinase (MMP) inhibitions, respectively. The
      modification toward their hydroxypyrazolino derivatives significantly improved
      the antioxidant activities of tetracycline and minocycline, as shown by three
      commonly used assays (DPPH, ABTS+, and superoxide scavenging). 12S-Hydroxy-1,12
      pyrazolinominocycline is a promising tetracycline-based antioxidant devoid of
      antibiotic properties and MMP inhibitory activity, which could be beneficial in
      the treatment of complications related to oxidative stress.

PMID- 15951187
TI  - Synthetic multifunctional pores that open and close in response to chemical
      stimulation.
AB  - Studies on synthetic multifunctional pores with external and internal active
      sites for ligand gating and noncompetitive blockage are presented, with emphasis
      on the contribution of external ligands to the characteristics of pore. A
      comparison between different synthetic multifunctional pores reveals that the
      location of functional groups in rigid-rod beta-barrel pores is precisely
      reflected in the function: molecular recognition at the outer barrel surface
      results in pore opening, while molecular recognition at the inner barrel surface
      results in pore closing. Negligible nonspecific leakage, disappearance of pH
      gating, inhibition of intervesicular pore transfer, and maybe also the flickering
      of currents of single open pores characterize external ligands as adhesive
      cushions that liberate the pore from lateral pressure exerted by the surrounding
      membrane. Refined molecular models show good agreement with pore design and
      experimental facts with regard to function.

PMID- 15951188
TI  - Microscopy and single molecule detection in photosynthesis.
AB  - Progress in various fields of microscopy techniques brought up enormous
      possibilities to study the photosynthesis down to the level of individual pigment
      protein complexes. The aim of this review is to present recent developments in
      the photosynthesis research obtained using such highly advanced techniques. Three
      areas of microscopy techniques covering optical microscopy, electron microscopy
      and scanning probe microscopy are reviewed. Whereas the electron microscopy and
      scanning probe microscopy are used in photosynthesis mainly for structural
      studies of photosynthetic pigment-protein complexes, the optical microscopy is
      used also for functional studies.

PMID- 15951189
TI  - Radioactivity studies along fracture zones in areas around Galudih, East
      Singhbhum, Jharkhand, India.
AB  - The application of radon to delineate geological processes like faulting and
      deformation, groundwater flow and contamination have assumed considerable
      significance over the last decade due to low-level detection capabilities and
      long-distance time migration. Suitable modeling procedures have helped in
      quantification of radon emanation and migration along active and passive faults.
      In the present study, we have attempted to correlate the radionuclide content and
      the extent of fracturing. For this purpose, quartzites occurring around Galudih,
      Jharkhand State, India, have been investigated. The study includes fracture
      density measurements at selected outcrops and joint analyses to evaluate the
      relationship between radionuclides and mesoscopic fractures. Moreover,
      microstructural studies have also been performed to decipher any existing
      relationship between radionuclides and microscale deformation mechanisms. It has
      been found that the microstructural phenomena are more important than mesoscopic
      scale processes and the former controls the concentration of radionuclides in
      rocks.

PMID- 15951190
TI  - The metabolism of glycosaminoglycans is impaired in prion diseases.
AB  - It is well established that the conversion of PrP(C) to PrP(Sc) is the key event
      in prion disease biology. In addition, several lines of evidence suggest that
      glycosaminoglycans (GAGs) and in particular heparan sulfate (HS) may play a role
      in the PrP(C) to PrP(Sc) conversion process. It has been proposed that PrP(Sc)
      accumulation in prion diseases may induce aberrant activation of lysosomal
      activity, which has been shown to result in neurodegeneration in a number of
      diseases, especially lysosomal storage disorders. Among such diseases, only the
      ones resulting from defects in GAGs degradation are accompanied by secretion of
      large amounts of GAG metabolites in urine. In this work, we show that GAGs are
      secreted in the urine of prion-infected animals and humans, and surprisingly,
      also in the urine of mice ablated for the PrP gene. We hypothesize that both the
      presence of PrP(Sc) or the absence of PrP(C) may alter the metabolism of GAGs.

PMID- 15951191
TI  - Reduced hippocampal neurogenesis in R6/2 transgenic Huntington's disease mice.
AB  - We investigated whether cell proliferation and neurogenesis are altered in R6/2
      transgenic Huntington's disease mice. Using bromodeoxyuridine (BrdU), we found a
      progressive decrease in the number of proliferating cells in the dentate gyrus of
      R6/2 mice. This reduction was detected in pre-symptomatic mice, and by 11.5
      weeks, R6/2 mice had 66% fewer newly born cells in the hippocampus. The results
      were confirmed by immunohistochemistry for the cell cycle markers Ki-67 and
      proliferating cell nuclear antigen (PCNA). We did not observe changes in cell
      proliferation in the R6/2 subventricular zone, indicating that the decrease in
      cell proliferation is specific for the hippocampus. This decrease corresponded to
      a reduction in actual hippocampal neurogenesis as assessed by double
      immunostaining for BrdU and the neuronal marker neuronal nuclei (NeuN) and by
      immunohistochemistry for the neuroblast marker doublecortin. Reduced hippocampal
      neurogenesis may be a novel neuropathological feature in R6/2 mice that could be
      assessed when evaluating potential therapies.

PMID- 15951192
TI  - Decreased expression and impaired function of muscarinic acetylcholine receptors
      in the rat hippocampus following transient forebrain ischemia.
AB  - In this study, we investigated whether transient cerebral ischemia affects the
      function and molecular expression of specific muscarinic cholinergic receptors.
      Our results show that in contrast to the GABA-B and A1 adenosine receptor
      systems, the ability of muscarinic receptors to attenuate evoked excitatory
      responses at vulnerable CA1 synapses is significantly attenuated by 18 h
      following reperfusion. This attenuation in efficacy was restricted to the
      vulnerable CA1 subfield, as no significant change in muscarinic receptor-mediated
      attenuation of evoked responsiveness was observed within post-ischemic dentate
      granule cell synapses. Expression analysis revealed that the mRNA and
      immunoreactive protein levels for individual types of muscarinic receptors
      respond differently and uniquely to transient cerebral ischemia insult. Of
      particular interest is the m4 subtype of receptor, whose mRNA and protein
      expression levels were significantly diminished within the hippocampus by 12 and
      24 h following reperfusion, respectively. As the m4 muscarinic receptor localizes
      to presynaptic terminals within the hippocampus, a decrease in its expression
      could account for the impaired functional responsiveness of the muscarinic
      receptor system following ischemic insult. Taken together, these results
      demonstrate that transient forebrain ischemia leads to dynamic alterations in the
      gene expression, protein prevalence, and functionality of muscarinic receptors in
      the post-ischemic hippocampus at times preceding the degeneration of the
      vulnerable neurons.

PMID- 15951193
TI  - Optimal pH strategy for selective cerebral perfusion.
AB  - OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior
      to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures.
      Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared
      pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs
      (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management,
      underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90
      min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and
      hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood
      sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed
      at the following time points: baseline, after 30 min cooling (20 degrees C), 30
      min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked
      potentials (VEP) were assessed at baseline and monitored for 2h during recovery.
      Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7
      postoperative days. RESULTS: There were no significant differences between the
      groups at baseline. CBF was significantly higher at the end of cooling, and after
      30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also
      higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to
      values close to baseline after rewarming (P=ns). VEP suggested a trend towards
      improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there
      were no significant differences in neurobehavioral score: (alpha-stat versus pH
      stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7.
      CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more
      effective metabolic suppression than pH-stat, with lower CBF. Clinically, the
      better preservation of cerebral autoregulation during alpha-stat perfusion should
      reduce the risk of embolization.

PMID- 15951194
TI  - In vivo effects of hypothermia on the microcirculation during extracorporeal
      circulation.
AB  - OBJECTIVE: Induced hypothermia has been shown to be protective during cardiac
      surgery, but also in traumatic, ischemic, burn, and neurological injury. In
      previous in vivo animal experiments, we documented increased
      leukocyte/endothelial (L/E) cell interaction following normothermic
      extracorporeal blood circulation (ECC). This study was carried out to investigate
      whether reduced core temperature during ECC affects the damage to the
      microcirculation as evidenced by leukocyte adherence and edema formation.
      METHODS: Intravital fluorescence microscopy was used on the dorsal skinfold
      chamber preparation in Syrian golden hamsters. ECC was introduced via a micro
      rollerpump (1 ml/min) and a 60 cm silicon tube (1mm inner diameter) shunted
      between the carotid artery and the jugular vein after application of 300IE
      Heparin/kg per body weight. Experiments were performed in chronically
      instrumented, awake animals (age 10-14 weeks, weight 65-75 g). Animals of the
      experimental group were cooled to 18 degrees C body temperature while ECC,
      followed by a rewarming period (n=7), controls experienced ECC under normothermia
      (37 degrees C, n=7). RESULTS: 30 min ECC at 18 degrees C resulted in a decrease
      of rolling and adherent leucocytes (stickers) in postcapillary venules after 1, 4
      and 8h compared with the control group (119+/-46 vs. 274+/-113 n/mm2, P<0.05,
      mean+/-SD; n=7 in each group). Functional capillary density was significantly
      reduced during hypothermia (80+/-16 vs. 148+/-16 cm/cm2, P<0.05), but restored
      after rewarming. In contrast, edema formation was markedly increased during
      hypothermia. CONCLUSIONS: Hypothermia during ECC significantly reduced L/E cell
      interaction in the early post-ECC period. Hypothermia markedly reduced
      microvascular perfusion, but was completely restored upon rewarming. Despite a
      reduced number of adherent leukocytes, no protection of endothelial barrier
      function was seen as a consequence of induced hypothermia.

PMID- 15951195
TI  - Gastric tip necrosis.

PMID- 15951196
TI  - Implantation of the Jarvik 2000 left-ventricular-assist-device: role of the
      maxillofacial surgeon.
AB  - The Jarvik 2000 system of axial-flow LVAD-is implanted for permanent mechanical
      circularly support in patients with end-stage heart failure waiting to undergo
      heart transplantation. The battery is connected with a power plug to the
      percutaneous skull-mounted footplate, which is monocortically fixated to the
      retro auricular bone. Patient selection should be highly specific, including
      careful preoperative evaluation. No device failures have been published so far,
      but complications can occur due to heparinisation. We describe the procedure from
      the perspective of the maxillofacial surgeon and give suggestions to prevent
      surgical complications.

PMID- 15951197
TI  - Recurrent spontaneous esophageal rupture.
AB  - Spontaneous esophageal rupture is an uncommon and poorly understood condition.
      Recurrent rupture is extremely rare, with only one previously reported case in
      the literature. Here, we present a case series of two patients who had recurrent
      ruptures, and discuss the principles underlying the management of such cases.

PMID- 15951198
TI  - Lovastatin-induced PC-12 cell differentiation is associated with RhoA/RhoA kinase
      pathway inactivation.
AB  - Relatively little is known about the relationship between cellular lipid
      composition and the ability of neuroblasts to elaborate axonal and dendritic
      processes. We have studied the role of cholesterol and non-sterol isoprenoids
      during neurite outgrowth in PC-12 cells using inhibitors of cholesterol
      biosynthesis that act at different points in the biosynthetic pathway. We provide
      evidence that inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase leads to extensive, sterol-dependent neurite outgrowth, via a mechanism
      that is independent of the requirement for sterols during proliferation. This
      effect is prevented by non-sterol mevalonate derivatives, suggesting the
      involvement of protein prenylation in the regulation of neurite outgrowth.
      Furthermore, we show that lovastatin inhibits both RhoA activation and Cofilin
      phosphorylation, while geranylgeraniol reverses these effects. Finally, the
      effect of geranylgeraniol on neurite outgrowth is prevented by Y-27632, an
      inhibitor of RhoA kinase. Taken together, our results suggest that inhibition of
      geranylgeraniol synthesis causes sterol-dependent neurite outgrowth in a process
      that is mediated by inhibition of RhoA signaling.

PMID- 15951199
TI  - Characterization of 16 human G protein-coupled receptors expressed in baculovirus
      infected insect cells.
AB  - Understanding the three-dimensional structure of G protein-coupled receptors
      (GPCRs) has been limited by the technical challenges associated with expression,
      purification, and crystallization of membrane proteins, and their low abundance
      in native tissue. In the first large-scale comparative study of GPCR protein
      production using recombinant baculovirus, we report the characterization of 16
      human receptors. The GPCRs were produced in three insect cell lines and
      functional protein levels monitored over 72 h using radioligand binding assays.
      Different GPCRs exhibited widely different expression levels, ranging from less
      than 1 pmol receptor/mg protein to more than 250 pmol/mg. No single set of
      conditions was suitable for all GPCRs, and large differences were seen for the
      expression of individual GPCRs in different cell lines. Closely related GPCRs did
      not share similar expression profiles; however, high expression (greater than 20
      pmol/mg) was achieved for over half the GPCRs in our study. Overall, the levels
      of protein production compared favourably to other published systems.

PMID- 15951200
TI  - cDNA cloning and genomic structure of grass carp (Ctenophayngodon idellus) beta2
      microglobulin gene.

PMID- 15951201
TI  - Construct validity of the DynaPort KneeTest: a comparison with observations of
      physical therapists.
AB  - OBJECTIVE: To assess the construct validity of the DynaPort KneeTest (KneeTest),
      which is a performance-based test to assess functioning of patients with knee
      osteoarthritis (OA). Scores on the KneeTest (KneeScore) were compared with
      observations of physical therapists of the patients' functional disability. The
      reliability of these observations was also assessed. METHOD: Twelve physical
      therapists received identical video tapes showing the performance of 33 patients
      on the KneeTest. Each physical therapist rated the functional disability of each
      patient, performing the 23 activities of the KneeTest, on 23 Visual Analogue
      Scales (VAS(activity)). The 23 VAS(activity) scores were averaged into a
      VAS(average) score. At the end of the test, an overall rating for the general
      performance of the patient was given on a VAS(overall). Inter-observer
      Reliability was assessed for the VAS(activity) scores, VAS(average), and the
      VAS(overall). RESULTS: Inter-observer reliability of the VAS(average) was higher
      (ICC 0.85, 95% CI 0.74-0.92) than the VAS(overall) (ICC 0.65, 95% CI 0.51-0.77).
      The correlation between the KneeScore and the VAS(average), averaged over the 12
      physiotherapists, was 0.86. CONCLUSION: The construct validity of the KneeTest
      was supported by the strong correlation with the ratings of the patients'
      disability by physical therapists. Given these findings and the high test-retest
      reliability of the KneeTest that was found in our previous study, we conclude
      that the KneeTest is a valid measure for assessing functioning in orthopedic and
      physical therapy research in patients with knee-OA before and after total knee
      replacement. Longitudinal validity has to be evaluated yet.

PMID- 15951202
TI  - Identification of an urinary metabolite profile associated with osteoarthritis.
AB  - OBJECTIVE: Osteoarthritis (OA) is one of the most common diseases among the
      elderly. The main characteristic is the progressive destruction of articular
      cartilage. We lack quantitative and sensitive biomarkers for OA to detect changes
      in the joints in an early stage of the disease. In this study, we investigated
      whether a urinary metabolite profile could be found that could serve as a
      diagnostic biomarker for OA in humans. We also compared the profile we obtained
      previously in the guinea pig spontaneous OA model. METHODS: Urine samples of 92
      participants (47 non-OA controls and 45 individuals with radiographic OA of the
      knees or hips) were selected from the Johnston County Osteoarthritis Project
      (North Carolina, USA). Participants ranged in age from 60 to 84 years. Samples
      were measured by 1H nuclear magnetic resonance spectroscopy (NMR) with subsequent
      principal component discriminant analysis and partial least squares regression
      analysis. RESULTS: Differences were observed between urine NMR spectra of OA
      cases and controls (P<0.001 for both male and female subjects). A metabolite
      profile could be determined which was strongly associated with OA. This profile
      largely resembled the profile previously identified for guinea pigs with OA
      (approximately 40 out of the approximately 125 signals of the human profile were
      present in the guinea pig profile as well). A correlation was found between the
      metabolite profile and radiographic OA severity (R2 = 0.82 (male); R2 = 0.93
      (female)). CONCLUSION: This study showed that a urine metabolite profile may
      serve as a novel discriminating biomarker of OA.

PMID- 15951203
TI  - Genetics of chondrocalcinosis.
AB  - Rapid developments in genetic analysis have enabled the dissection of a variety
      of arthropathies that are inherited in a Mendelian manner. These disorders
      include calcium crystal arthropathies such as calcium pyrophosphate dihydrate
      deposition (CPPD) disease and hydroxyapatite deposition disease. In CPPD disease,
      mutations in a recently discovered gene, ANKH, have been demonstrated in five
      affected families and may also be associated with the idiopathic deposition of
      calcium pyrophosphate dihydrate crystals. The product of ANKH appears to be
      involved in cellular transport of inorganic pyrophosphate (PPi) and mutations in
      ANKH have been shown to have a significant impact on the regulation of intra- and
      extracellular levels of PPi. In families with hydroxyapatite deposition disease,
      no gene locus has yet been linked to the disorder.

PMID- 15951204
TI  - Osmotic and diffusive properties of intracellular water in camel erythrocytes:
      effect of hemoglobin crowdedness.
AB  - Camel erythrocytes have exceptional osmotic resistance and is believed to be due
      to augmented water-binding associated with the high hydrophilicity of camel
      hemoglobin. In practical terms this means that the proportion of osmotically non
      removable water in camel erythrocytes is nearly 3-fold greater than that in human
      erythrocytes (approximately 65 vs approximately 20%). The relationship between
      water diffusion and the osmotic characteristics of intracellular water is the
      subject of this report. The amount of osmotically inactive water is 2-fold
      greater in camel hemoglobin solution in vitro compared to that of human, but
      water diffusion does not differ in camel and human hemoglobin solutions. However,
      the evaluation of water diffusion by magnetic resonance measurements in camel
      erythrocytes revealed approximately 15% lower apparent diffusion coefficient
      (ADC) compared with human erythrocytes. When human erythrocytes were dehydrated
      to the level of camel erythrocytes, their osmotic and water diffusion properties
      were similar. These results show that a lower ADC is associated with a more
      pronounced increase in osmotically inactive water fraction. It is proposed that
      increased hemoglobin hydrophilicity allows not only augmented water-binding, but
      also a closer hemoglobin packaging in vivo, which in turn is associated with
      slower ADC and increased osmotic resistance.

PMID- 15951205
TI  - Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: evidence
      for a skeletal muscle-to-fat signaling pathway.
AB  - Interleukin-15 (IL-15) is a cytokine which is highly expressed in skeletal muscle
      tissue, and which has anabolic effects on skeletal muscle protein dynamics both
      in vivo and in vitro. Additionally, administration of IL-15 to rats and mice
      inhibits white adipose tissue deposition. To determine if the action of IL-15 on
      adipose tissue is direct, the capacity of cultured murine 3T3-L1 preadipocytes
      and adipocytes to respond to IL-15 was examined. IL-15 administration inhibited
      lipid accumulation in differentiating 3T3-L1 preadipocytes, and stimulated
      secretion of the adipocyte-specific hormone adiponectin by differentiated 3T3-L1
      adipocytes. The latter observation constitutes the first report of a cytokine or
      growth factor which stimulates adiponectin production. IL-15 mRNA expression by
      cultured 3T3-L1 adipogenic cells and C2C12 murine skeletal myogenic cells was
      also examined. Quantitative real-time PCR indicated IL-15 mRNA was expressed by
      C2C12 skeletal myogenic cells, and was upregulated more than 10-fold in
      differentiated skeletal myotubes compared to undifferentiated myoblasts. In
      contrast, 3T3-L1 cells expressed little or no IL-15 mRNA at either the
      undifferentiated preadipocyte or differentiated adipocyte stages. These findings
      provide support for the hypothesis that IL-15 functions in a muscle-to-fat
      endocrine axis which modulates fat:lean body composition and insulin sensitivity.

PMID- 15951206
TI  - Ultrastructural, immunohistochemical and biochemical analysis of
      glycosaminoglycans and proteoglycans in the mouse pubic symphysis during
      pregnancy.
AB  - During pregnancy, an interpubic ligament is formed in the mouse pubic symphysis.
      In late stages, this ligament undergoes "relaxation" to allow proper delivery,
      which is expected on the 19th day. Proteoglycans and hyaluronic acid play an
      important role in the remodeling of the extracellular matrix in these tissues.
      Glycosaminoglycans and proteoglycans were studied by electron microscopic,
      immunohistochemical and biochemical methods in samples of mouse pubic symphysis
      from the 12th to 18th day of pregnancy. At the ultrastructural level, using
      cuprolinic blue and enzymatic digestion by chondroitin lyases, two types of
      proteoglycan filaments were observed in the fibrocartilage on the 12th day, as
      well as in D 15, D 17 and D 18 pubic ligaments. The only sulfated
      glycosaminoglycan in these filaments was chondroitin sulfate, as shown by
      chondroitin lyase treatment. Their electrophoretic mobility, before and after
      enzymatic degradation, corroborated this inference. The ratio of chondroitin
      sulfate/dry weight of symphysis showed two phases of increase: between D12 and D
      15, and between D 17 and D 18. We suggest that the first corresponds mainly to an
      increase in decorin when the ligament is formed, and the second to versican,
      during "relaxation". Versican and hyaluronic acid, working as water holding
      molecules would be responsible for the hydration of the ligament at the end of
      pregnancy, allowing an increase in resiliency. The presence of hyaluronic acid
      was confirmed by labeling with HA-probe in the perichondrium, fibrocartilage and
      ligament. The role of collagen fibers as physical restrictors of the complete
      expansion of glycosaminoglycans and hyaluronic acid in tissue is discussed.

PMID- 15951207
TI  - Proliferative feeder cells support prolonged expansion of human embryonic stem
      cells.
AB  - Long-term proliferation of human embryonic stem (hES) cells is currently achieved
      by co-culturing with mitotically inactive primary mouse embryonic fibroblasts
      (mEFs), which serve as feeder cells. This study explores the possibility that
      proliferative mEFs can be used as feeder cells to maintain the prolonged
      expansion of hES cells. All undifferentiated hES cell clumps were re-plated on
      six different densities of proliferative mEFs. hES colonies cultured on 1 x 10(5)
      - 5 x 10(5) proliferative mEFs amplified over 130 days of continuous culture and
      remained undifferentiated, as did those cultured on mitotically inactive mEFs.
      This suggests that certain densities of proliferative mEFs can maintain the
      propagation of hES cells, which may be helpful for identifying the cytokines and
      adhesion molecules that are required for their self-renewal.

PMID- 15951208
TI  - In vitro differentiation of human dental follicle cells with dexamethasone and
      insulin.
AB  - The dental follicle is an ectomesenchymally derived connective tissue harboring
      precursor cells for the tooth supporting apparatus. In this study, we examined
      gene expression of freshly isolated human dental follicle cells during osteogenic
      differentiation in vitro. These plastic adherent fibroblastic cells express Notch
      1, nestin and vimentin. We differentiated dental follicle cells with
      dexamethasone or insulin-based protocols into membrane-like structures containing
      mineralizing foci. An analysis of mineralized tissue with atomic force microscopy
      illustrated a bone and cementum-like structure. A real-time RT-PCR analysis was
      developed to investigate expression of typical osteoblast or cementoblast related
      genes during differentiation. Gene expressions of osteocalcin (OCN), bone
      morphogenic protein (BMP)-2 and nestin were increased during the both
      differentiation approaches. Our work demonstrates differentiation of dental
      follicle cells with an insulin-based protocol for the first time.

PMID- 15951209
TI  - Effects of growth hormone secretagogues on the release of adenohypophyseal
      hormones in young and old healthy dogs.
AB  - The effects of three growth hormone secretagogues (GHSs), ghrelin, growth hormone
      releasing peptide-6 (GHRP-6), and growth hormone-releasing hormone (GHRH), on the
      release of adenohypophyseal hormones, growth hormone (GH), adrenocorticotropic
      hormone (ACTH), thyroid-stimulating hormone (TSH), luteinising hormone (LH),
      prolactin (PRL) and on cortisol were investigated in young and old healthy Beagle
      dogs. Ghrelin proved to be the most potent GHS in young dogs, whereas in old dogs
      GHRH administration was associated with the highest plasma GH concentrations. The
      mean plasma GH response after administration of ghrelin was significantly lower
      in the old dogs compared with the young dogs. The mean plasma GH concentration
      after GHRH and GHRP-6 administration was lower in the old dogs compared with the
      young dogs, but this difference did not reach statistical significance. In both
      age groups, the GHSs were specific for GH release as they did not cause
      significant elevations in the plasma concentrations of ACTH, cortisol, TSH, LH,
      and PRL. It is concluded that in young dogs, ghrelin is a more powerful
      stimulator of GH release than either GHRH or GHRP-6. Ageing is associated with a
      decrease in GH-releasing capacity of ghrelin, whereas this decline is
      considerably lower for GHRH or GHRP-6.

PMID- 15951210
TI  - Tail-biting in outdoor pig production.
AB  - A study was performed in five identical outdoor production units in the same
      geographic area using growing-finishing pigs of similar genetic makeup, age, diet
      and feed management. The severity of tail-biting (TS) was scored 1-4. The average
      group prevalence of bitten tails at slaughter on different farms was between
      14.1+/-2.1% and 20.1+/-3.0% (P<0.05). The odds of a barrow being bitten were 2.9
      times higher than those for a gilt. The most frequently recorded score of bitten
      tails was TS3, indicating moderate wounds with low grade infection. The
      prevalence of bitten barrows was positively correlated with the percentage of
      gilts in a group (r = 0.54, P<0.001). Pigs with zero TS score had no
      significantly higher weights at slaughter compared to pigs with a score of TS1.
      As the TS increased from 1 to 4, weights decreased (TS 1 to TS 2 to 4, P<0.05).
      TS 3 and 4 were positively (P<0.001) associated with subsequent carcass
      condemnation. We concluded that outdoor rearing does not prevent tail-biting.

PMID- 15951211
TI  - An implementation of the nudged elastic band algorithm and application to the
      reaction mechanism of HGXPRTase from Plasmodium falciparum.
AB  - The understanding of transition processes, such as chemical reactions, is a
      central topic in theoretical molecular science. A common approach for
      investigating such processes is to calculate paths between reactant and product
      structures that are representative of the transition. Many approaches have been
      proposed to determine such paths but, in this paper, we examine the nudged
      elastic band algorithm which was recently introduced by Jonsson and co-workers
      and has been used to study a wide range of transition problems. We describe our
      implementation of the method in the simulation program Dynamo and some
      modifications to the original algorithm that we found improve its efficiency. The
      use of the method is illustrated by an application to the reaction mechanism of
      the enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase from
      Plasmodium falciparum.

PMID- 15951212
TI  - Distribution and ontogeny of glial fibrillary acidic protein in the snail
      Megalobulimus abbreviatus.
AB  - Glial fibrillary acidic protein (GFAP) is the major component of intermediate
      glial filaments in the central nervous system of many vertebrates and
      invertebrates. In vertebrates, this protein is mainly expressed in mature
      astrocytes and provides structural cell stability. The highly conserved structure
      and glial specificity of this protein have allowed studies of ontogeny and
      phylogeny using antibodies. The present study investigated the ontogenetic
      profile and molecular weight of GFAP in the snail, Megalobulimus abbreviatus,
      particularly in cerebral ganglia and subesophageal mass, by immunohistochemistry
      and immunoblotting. Our results confirm and extend previous studies about glial
      intermediate filaments in snails, showing: (i) a higher GFAP content in cerebral
      ganglia than in subesophageal mass; (ii) a developmental increase of GFAP
      immunocontent in cerebral ganglia, as described in Vertebrates; and (iii) an
      electrophoretic band for GFAP of approximately 55 kDa.

PMID- 15951213
TI  - Partial cloning and expression of mRNA coding choline acetyltransferase in the
      spinal cord of the goldfish, Carassius auratus.
AB  - Choline acetyltransferase (ChAT, EC 2.3.1.6) synthesizes a neurotransmitter,
      acetylcholine in cholinergic neurons. ChAT is considered to be the most specific
      marker for cholinergic neurons. To obtain a better marker of the neurons, as the
      first step, we isolated a partial ChAT cDNA from the goldfish (Carassius auratus)
      brain by RT-PCR methods. The partial cDNA of the goldfish ChAT was composed of
      718 nucleotides. The amino acid sequence of the goldfish ChAT is approximately
      70% identical to those of mammalian and chicken ChAT. Northern blot analysis
      demonstrated that ChAT mRNA was expressed in the brain and the spinal cord of the
      goldfish, and much abundant in the spinal cord. In the spinal cord of the
      goldfish, ChAT-positive neurons were detected mainly in the ventral horn by in
      situ hybridization. In addition, fluorescence in situ hybridization combined with
      a retrograde labeling by using True Blue demonstrated ChAT mRNA positive neurons
      were exactly motoneurons. In the cord, putative presynaptic sympathetic neurons
      were also labeled.

PMID- 15951214
TI  - Immunomodulation after allogeneic bone marrow transplantation by CD4+CD25+
      regulatory T cells.
AB  - Graft-versus-host disease is a major complication after allogeneic bone marrow
      transplantation (BMT) caused by donor T cells. Immunosuppression mediated by
      CD4(+)CD25(+) regulatory T cells has been shown to ameliorate such pathogenic
      immune responses in animal models. Here, we summarize recent findings from
      experimental and clinical studies and propose a model for peripheral tolerance
      induction after BMT.

PMID- 15951216
TI  - STR data for the AmpFLSTR Identifiler loci in Bangladeshi and Indonesian
      populations.
AB  - Allele frequencies of 15 short tandem repeat (STR) loci, D8S1179, D21S11, D7S820,
      CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51,
      D5S818 and FGA, were analyzed in 127 unrelated Bangladeshi individuals and 105
      unrelated Indonesian individuals using the AmpFLSTR Identifiler kit. All STR loci
      in Bangladeshis and Indonesians were in the Hardy-Weinberg equilibrium.

PMID- 15951215
TI  - T cell epitope characterization in tandemly repetitive Trypanosoma cruzi B13
      protein.
AB  - Proteins containing tandemly repetitive sequences are present in several
      immunodominant protein antigens in pathogenic protozoan parasites. The tandemly
      repetitive Trypanosoma cruzi B13 protein is recognized by IgG antibodies from 98%
      of Chagas' disease patients. Little is known about the molecular mechanisms that
      lead to the immunodominance of the repeated sequences, and there is limited
      information on T cell epitopes in such repetitive antigens. We finely
      characterized the T cell recognition of the tandemly repetitive, degenerate B13
      protein by T cell lines, clones and PBMC from Chagas' disease cardiomyopathy
      (CCC), asymptomatic T. cruzi infected (ASY) and non-infected individuals (N).
      PBMC proliferative responses to recombinant B13 protein were restricted to
      individuals bearing HLA-DQA1*0501(DQ7), -DR1, and -DR2; B13 peptides bound to the
      same HLA molecules in binding assays. The HLA-DQ7-restricted minimal T cell
      epitope [FGQAAAG(D/E)KP] was identified with an overlapping combinatorial peptide
      library including all B13 sequence variants in T. cruzi Y strain B13 protein; the
      underlined small residues GQA were the major HLA contact residues. Among natural
      B13 15-mer variant peptides, molecular modeling showed that several variant
      positions were solvent (TCR)-exposed, and substitutions at exposed positions
      abolished recognition. While natural B13 variant peptide S15.9 seems to be the
      immunodominant epitope for Chagas' disease patients, S15.4 was preferentially
      recognized by CCC rather than ASY patients, which may be pathogenically relevant.
      This is the first thorough characterization of T cell epitopes of a tandemly
      repetitive protozoan antigen and may suggest a role for T cell help in the
      immunodominance of protozoan repetitive antigens.

PMID- 15951217
TI  - Physical determinants of cell organization in soft media.
AB  - Cell adhesion is an integral part of many physiological processes in tissues,
      including development, tissue maintenance, angiogenesis, and wound healing.
      Recent advances in materials science (including microcontact printing, soft
      lithography, microfluidics, and nanotechnology) have led to strongly improved
      control of extracellular ligand distribution and of the properties of the
      micromechanical environment. As a result, the investigation of cellular response
      to the physical properties of adhesive surfaces has become a very active area of
      research. Sophisticated use of elastic substrates has revealed that cell
      organization in soft media is determined by active mechanosensing at cell-matrix
      adhesions. In order to determine the underlying mechanisms, quantification and
      biophysical modelling are essential. In tissue engineering, theory might help to
      design new environments for cells.

PMID- 15951218
TI  - BMP antagonists: their roles in development and involvement in pathophysiology.
AB  - Bone morphogenetic proteins (BMPs) are phylogenetically conserved signaling
      molecules that belong to the transforming growth factor (TGF)-beta superfamily,
      and are involved in the cascades of body patterning and morphogenesis. The
      activities of BMPs are precisely regulated by certain classes of molecules that
      are recently recognized as BMP antagonists. BMP antagonists function through
      direct association with BMPs, thus prohibiting BMPs from binding their cognate
      receptors. In this review, the classification and functions of BMP antagonists
      will be discussed, especially focusing on the new family of tissue-specific BMP
      antagonists composed of uterine sensitization-associated gene 1 (USAG-1) and
      sclerostin.

PMID- 15951219
TI  - Bone morphogenetic proteins in craniofacial and periodontal tissue engineering:
      experimental studies in the non-human primate Papio ursinus.
AB  - The bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of
      the transforming growth factor-beta (TGF-beta) supergene family act as soluble
      signals for the de novo initiation of bone formation, sculpting the multicellular
      mineralized structures of the bone-bone marrow organ. The strikingly pleiotropic
      effects of BMPs/OPs spring from amino acid sequence variations in the carboxy
      terminal domain and in the transduction of distinct signalling pathways by
      individual Smad proteins after transmembrane serine/threonine kinase complexes of
      type I and II receptors. BMPs/OPs are the common molecular initiators deployed
      for embryonic development and the induction of bone formation and regeneration in
      postnatal osteogenesis. Naturally derived BMPs/OPs extracted and purified from
      baboon and bovine bone matrices induce complete regeneration of non-healing
      calvarial defects in the non-human primate Papio ursinus as well as the induction
      of cementogenesis and the morphogenesis of a periodontal ligament system with a
      faithful insertion of Sharpey's fibers into the newly formed cementum. gamma
      Irradiated recombinant human osteogenic protein-1 (hOP-1) delivered by xenogeneic
      bovine collagenous bone matrices completely regenerated and maintained the
      architecture of the induced bone after treatment of calvarial defects with single
      applications of doses of 0.1, 0.5 and 2.5mg hOP-1 per gram of carrier matrix. The
      long-term implantation of hOP-1 delivered by gamma-irradiated bovine bone
      matrices induced the regeneration of the three essential components of the
      periodontium, i.e. cementum, periodontal ligament and alveolar bone. The
      osteogenic proteins of the TGF-beta superfamily are sculpting tissue constructs
      that engineer skeletal tissue regeneration in molecular terms. The pleiotropy of
      the signalling molecules of the TGF-beta superfamily is highlighted by the
      redundancy of molecular signals initiating bone formation, including the TGF-beta
      isoforms per se, powerful inducers of endochondral bone formation but in the
      primate only. The induction of bone develops a mosaic structure in which members
      of the TGF-beta superfamily singly, synergistically and synchronously initiate
      and maintain tissue induction and morphogenesis.

PMID- 15951220
TI  - Plant gene expression in the age of systems biology: integrating transcriptional
      and post-transcriptional events.
AB  - The extensive mechanistic and regulatory interconnections between the various
      events of mRNA biogenesis are now recognized as a fundamental principle of
      eukaryotic gene expression, yet the specific details of the coupling between the
      various steps of mRNA biogenesis do differ, and sometimes dramatically, between
      the different kingdoms. In this review, we emphasize examples where plants must
      differ in this respect from other eukaryotes, and highlight a recurring trend of
      recruiting the conserved, versatile functional modules, which have evolved to
      support the general mRNA biogenesis reactions, for plant-specific functions. We
      also argue that elucidating the inner workings of the plant 'mRNA factory' is
      essential for accomplishing the ambitious goal of building the 'virtual plant'.

PMID- 15951221
TI  - Biogenesis of iron-sulfur proteins in plants.
AB  - Iron-sulfur (Fe-S) clusters are ubiquitous prosthetic groups required to sustain
      fundamental life processes. The assembly of Fe-S clusters and insertion into
      polypeptides in vivo has recently become an area of intense research. Many of the
      genes involved are conserved in bacteria, fungi, animals and plants. Plant cells
      can carry out both photosynthesis and respiration - two processes that require
      significant amounts of Fe-S proteins. Recent findings now suggest that both
      plastids and mitochondria are capable of assembling Fe-S proteins using assembly
      machineries that differ in biochemical properties, genetic make-up and
      evolutionary origin.

PMID- 15951222
TI  - Biophoton distress flares signal the onset of the hypersensitive reaction.
AB  - Detection of biophoton emission, a natural bioluminescence, has emerged as a non
      destructive method to mark the onset of the hypersensitive resistance reaction in
      Arabidopsis, bean and tomato. Rapid biophoton emission in Arabidopsis requires an
      intact R-gene signalling network and increased levels of cytosolic calcium and
      nitric oxide. The burst of biophotons precedes macroscopic symptoms by several
      hours and its timing is characteristic for specific gene-for-gene interactions.
      The ability to monitor biophoton emission from whole plants in real time should
      allow detailed dissection of plant defence responses.

PMID- 15951223
TI  - Green genes gleaned.
AB  - A recent paper by Ayumi Tanaka and colleagues identifying an Arabidopsis thaliana
      gene for 3,8-divinyl(proto)chlorophyllide 8-vinyl reductase brings a satisfying
      conclusion to the hunt for genes encoding enzymes for the steps in the
      chlorophyll biosynthetic pathway. Now, at least in angiosperm plants represented
      by Arabidopsis, genes for all 15 steps in the pathway from glutamyl-tRNA to
      chlorophylls a and b have been identified.

PMID- 15951224
TI  - The neural code for written words: a proposal.
AB  - How is reading, a cultural invention, coded by neural populations in the human
      brain? The neural code for written words must be abstract, because we can
      recognize words regardless of their location, font and size. Yet it must also be
      exquisitely sensitive to letter identity and letter order. Most existing coding
      schemes are insufficiently invariant or incompatible with the constraints of the
      visual system. We propose a tentative neuronal model according to which part of
      the occipito-temporal 'what' pathway is tuned to writing and forms a hierarchy of
      local combination detectors sensitive to increasingly larger fragments of words.
      Our proposal can explain why the detection of 'open bigrams' (ordered pairs of
      letters) constitutes an important stage in visual word recognition.

PMID- 15951225
TI  - Justifying all the fuss about false belief.
AB  - The classic study by Wimmer and Perner showed that children below the age of
      about 4 years of age fail to appreciate others' false beliefs. This opened the
      floodgates to the theory-of-mind research programme. Recently, a study by Riggs
      and Simpson has called the central challenge of false belief into question,
      reporting similar difficulties with true belief. I would argue, however, that not
      only should the acquisition of false belief remain a central concern but that we
      should think harder about it and its earlier manifestations.

PMID- 15951226
TI  - Continuity of the conceptual system across species.
AB  - In a recent neuroimaging study of macaque monkeys, Gil-da-Costa and colleagues
      reported that a distributed circuit of modality-specific properties represents
      macaques' conceptual knowledge of social situations. The circuit identified shows
      striking similarities to analogous circuits in humans that represent conceptual
      knowledge. This parallel suggests that a common architecture underlies the
      conceptual systems of different species, although with additional systems
      extending human conceptual abilities significantly.

PMID- 15951227
TI  - Monitoring DNA damage in indigenous blue mussels (Mytilus edulis) sampled from
      coastal sites in Denmark.
AB  - Damage to DNA detected by use of the single-cell gel electrophoresis (comet)
      assay was monitored in blue mussels, Mytilus edulis, sampled from coastal waters
      in Denmark. Mussels from five locations in Koge Bay, an area receiving wastewater
      from many industries and municipalities, were collected five times during 1999
      and six times in 2001. In 1999, both gill cells and haemolymph cells were
      examined, and sediments were sampled on three dates from the same five locations.
      In the autumn of 1999, mussels were also collected at six reference sites without
      known pollution. Results showed a significantly higher level of DNA damage in
      gill cells compared with haemolymph cells. Because of this, only gill cells were
      sampled for the monitoring in 2001. Levels of DNA damage, expressed as tail
      moments, were significantly higher for the mussels in Koge Bay when compared with
      levels of DNA damage in mussels from the non-polluted coastal areas. No clear
      seasonal variation was demonstrated. Analysis of the correlation between
      chromium, nickel, cadmium and mercury in sediments and tail moments in haemolymph
      and gill cells from the five sites showed a statistically significant positive
      correlation between tail moments and chromium, nickel and cadmium (P<0.01). The
      overall conclusion was that the comet assay on blue mussels could be useful for
      screening of genotoxic pollution in marine waters.

PMID- 15951228
TI  - Using Raman spectroscopy to identify mixite minerals.
AB  - Raman spectroscopy has been used to identify whether or not a selection of
      minerals labelled as mixites (formula BiCu6(AsO4)3(OH)6.3H2O) are correctly
      marked. Of the four samples, two samples are shown to be potentially mixites
      because of the presence of the characteristic Raman spectra of (AsO4)3- units and
      (HAsO4)- units, characterised by bands at around 803 and 833 cm(-1). Two of the
      minerals are shown to be predominantly carbonates. Bands are observed at 3473.9
      and 3470.3 cm(-1) for the two mixite samples. Bands observed in the region 880
      910 cm(-1) and in the 867-870 cm(-1) region are assigned to the AsO stretching
      vibrations of (HAsO4)2- and (H2AsO4)- units. Whilst bands at around 803 and 833
      cm(-1) are assigned to the stretching vibrations of uncomplexed (AsO4)3- units.
      Intense bands observed at 473.7 and 475.4 cm(-1) are assigned to the nu4 bending
      mode of AsO4 units. Bands observed at around 386.5, 395.3 and 423.1 cm(-1) are
      assigned to the nu2 bending modes of the HAsO4 (434 and 400 cm(-1)) and the AsO4
      groups (324 cm(-1)). Raman spectroscopy lends itself to the identification of
      minerals on host matrices and is especially useful for the identification of
      mixites.

PMID- 15951229
TI  - Photoacoustic phase study on the frequency dependence of phase angle and triplet
      state lifetime of Nd(III)-acetylacetonate.
AB  - The amplitude and phase of the photoacoustic (PA) signal generated in the rare
      earth complex powder of Nd(III)-acetylacetonate (Nd(AA)3) were examined. By using
      the reasonably simplified formula about phase angle at the wavelengths assigned
      to pi-pi* transition of ligand and f-f transitions of Nd3+, the instrumental
      contribution to phase angle at different chopping frequency was calculated. The
      frequency dependence of sample phase angle, the relative phase angle shift caused
      by instrumental factors and the calculation of triplet state lifetime of sample
      under study were also discussed. Being independent of sample, the instrumental
      contribution to phase angle was regarded as a parameter representing the
      situations of instruments and measurement and it became an approach to calculate
      the relaxation time of ligand in rare earth complex.

PMID- 15951230
TI  - Density functional theory study of the FT-IR spectra of phthalimide and N
      bromophthalimide.
AB  - Fourier transform infrared (FT-IR) spectra of phthalimide and N-bromophthalimide
      have been recorded in the range of 4000-400 cm-1. With the hope of providing more
      and effective information on the fundamental vibrations, a normal coordinate
      analysis has been performed on phthalimide and N-bromophthalimide, by assuming
      C2v symmetry. Density functional theory (DFT)-Beck3-Lee-Yang-Parr (B3LYP) levels
      with 6-31G* and 6-311+G** basis sets have been employed in quantum chemical
      analysis. The computational frequencies are in good agreement with the observed
      results. The theoretical spectra obtained along with intensity data agree well
      with the observed spectra.

PMID- 15951231
TI  - Study on the interaction between nucleic acid and Eu3+-oxolinic acid and the
      determination of nucleic acid using the resonance light scattering technique.
AB  - At pH 9.75, the resonance light scattering (RLS) intensity of OA-Eu3+ system is
      greatly enhanced by nucleic acid. Based on this phenomenon, a new quantitative
      method for nucleic acid in aqueous solution has been developed. Under the optimum
      condition, the enhanced RLS is proportional to the concentration of nucleic acid
      in the range of 1.0x10(-9) to 1.0x10(-6)g/ml for herring sperm DNA, 8.0x10(-10)
      to 1.0x10(-6) g/ml for calf thymus DNA and 1.0x10(-9) to 1.0x10(-6) g/ml for
      yeast RNA, and their detection limits are 0.020, 0.011 and 0.010 ng/ml,
      respectively. Synthetic samples and actual samples were satisfactorily
      determined. In addition, the interaction mechanism between nucleic acid and OA
      Eu3+ is also investigated.

PMID- 15951232
TI  - Synthesis, structure, infrared and fluorescence spectra of new rare earth
      complexes with 6-hydroxy chromone-3-carbaldehyde benzoyl hydrazone.
AB  - A novel 6-hydroxy chromone-3-carbaldehyde benzoyl hydrazone ligand and its four
      complexes, [LnL2(NO3)2]NO3 [Ln = Eu(1), Sm(2), Tb(3), Dy(4)], were synthesized.
      The complexes were characterized by the elemental analyses, molar conductivity
      and IR spectra. The crystal and molecular structure of Sm(III) complex was
      determined by single-crystal X-ray diffraction: crystallized in the triclinic
      system, space group P-1, Z = 1, a = 11.037(4) A, b = 14.770(5) A, c = 15.032(7)
      A, alpha = 60.583(4), beta = 75.528(7), gamma = 88.999(4), R1 = 0.0349. The
      fluorescence properties of complexes in the solid state and in the organic
      solvent were studied in detail, respectively. Under the excitation of ultraviolet
      light, strong red fluorescence of solid europium complex was observed. But the
      green fluorescence of solid terbium complex was not observed. These observations
      show that the ligand favor energy transfers to the emitting energy level of Eu3+.
      Some factors that influence the fluorescent intensity were also discussed.

PMID- 15951234
TI  - Structural and thermal characterization of ternary complexes of piroxicam and
      alanine with transition metals: uranyl binary and ternary complexes of piroxicam.
      Spectroscopic characterization and properties of metal complexes.
AB  - Ternary Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and UO2(II) complexes with
      piroxicam (Pir) drug (H2L1) and dl-alanine (Ala) (HL2) and also the binary
      UO2(II) complex with Pir were studied. The structures of the complexes were
      elucidated using elemental, IR, molar conductance, magnetic moment, diffused
      reflectance and thermal analyses. The UO2(II) binary complex was isolated in 1:2
      ratio with the formula [UO2(H2L)2](NO3)2. The ternary complexes were isolated in
      1:1:1 (M:H2L1:L2) ratios. The solid complexes were isolated in the general
      formulae [M(H2L)(L2)(Cl)n(H2O)m].yH2O (M=Fe(III) (n=2, m=0, y=1), Co(II) (n=1,
      m=1, y=2) and Ni(II) (n=1, m=1, y=0)); [M(H2L)(L2)](X)z.yH2O (M=Cu(II) (X=AcO,
      z=1, y=0), Zn(II) (X=AcO, z=1, y=3) and UO2(II) (X=NO3, z=1, y=2)). Pir behaves
      as a neutral bidentate ligand coordinated to the metal ions via the pyridine-N
      and carbonyl-O groups, while Ala behaves as a uninegatively bidentate ligand
      coordinated to the metal ions via the deprotonated carboxylate-O and amino-N. The
      magnetic and reflectance spectral data show that the complexes have octahedral
      geometry except Cu(II) and Zn(II) complexes have tetrahedral structures. The
      thermal decomposition of the complexes was discussed in relation to structure,
      and the thermodynamic parameters of the decomposition stages were evaluated.

PMID- 15951233
TI  - UV-vis, IR and 1H NMR spectroscopic studies of some mono- and bis-azo-compounds
      based on 2,7-dihydroxynaphthalene and aniline derivatives.
AB  - The absorption spectra of mono- and bis-azo-derivatives obtained by coupling the
      diazonium salts of aromatic amines and 2,7-dihydroxynaphthalene have been studied
      in six organic solvents. The different absorption bands have been assigned and
      the effect of solvents on the charge transfer band is also discussed. The
      diagnostic IR spectral bands and 1H NMR signals are assigned and discussed in
      relation to molecular structure. Also, semi-empirical molecular orbital
      calculations using the atom superposition and electron delocalization molecular
      orbital (ASED-MO) theory have been performed to investigate the molecular and
      electronic structures of these compounds. According to these calculations, an
      intramolecular hydrogen bonding is essential for stabilization of such molecules.

PMID- 15951235
TI  - Synthesis and spectroscopic studies of copper(II) and nickel(II) complexes
      containing hydrazonic ligands and heterocyclic coligand.
AB  - Two types of copper(II) and nickel(II) complexes derived from benzophenone
      anthranoylhydrazone (L1), 2-acetonaftanone anthranoylhydrazone (L2), 4
      phenylacetonaftonone anthranoylhydrazone (L3), benzophenone salicyoylhydrazone
      (L4), 2-acetonaftanon salicyoylhydrazone (L5), 4-phenylacetonaftanon
      salicyoylhydrazone (L6) and bidentate heterocyclic base [1,10-phenanthroline
      (phen)] with general stoichiometry [ML2] and [ML(phen)]Cl have been synthesized
      and characterized by elemental analysis, infrared spectra, UV-vis electronic
      absorption spectra and magnetic susceptibility measurements. The effect of
      varying pH and solvent on the absorption behavior of both ligands and complexes
      have been investigated. According to the IR spectra, the ligands act as monobasic
      bidentate and coordination takes place in the enol tautomeric form.

PMID- 15951236
TI  - Flux of sterol intermediates in a yeast strain deleted of the lanosterol C-14
      demethylase Erg11p.
AB  - Lanosterol C-14 demethylase Erg11p of the yeast Saccharomyces cerevisiae
      catalyzes the enzymatic step following formation of lanosterol by the lanosterol
      synthase Erg7p in lipid particles (LP). Localization experiments employing
      microscopic inspection and cell fractionation revealed that Erg11p in contrast to
      Erg7p is associated with the endoplasmic reticulum (ER). An erg11Delta mutation
      in erg3Delta background, which is required to circumvent lethality of the erg11
      defect, did not only change the sterol pattern but also the sterol distribution
      within the cell. Whereas in wild type the plasma membrane was highly enriched in
      ergosterol and LP harbored large amounts of sterol precursors in the form of
      steryl esters, sterol intermediates were more or less evenly distributed among
      organelles of erg11Delta erg3Delta. This distribution is not result of the
      erg3Delta background, because in the erg3Delta strain the major intermediate
      formed, ergosta-7,22-dienol, is also highly enriched in the plasma membrane
      similar to ergosterol in wild type. These results indicate that (i) exit of
      lanosterol from LP occurs independently of functional Erg11p, (ii) random supply
      of sterol intermediates to all organelles of erg11Delta erg3Delta appears to
      compensate for the lack of ergosterol in this mutant, and (iii) preferential
      sorting of ergosterol in wild type, but also of ergosta-7,22-dienol in erg3Delta,
      supplies sterol to the plasma membrane.

PMID- 15951237
TI  - Bile acid induces hydrophobicity-dependent membrane alterations.
AB  - Elevated concentrations of fecal bile acids are a known risk factor for colon
      cancer, owing to alterations in cellular signaling. In colonic cells, where bile
      acid uptake is minimal, the hydrophobicity-induced membrane perturbation and
      alterations have been proposed, but these membrane alterations are largely
      uncharacterized. In this study, we examined the determinants and characteristics
      of bile acid-induced membrane alterations, utilizing PKCalpha activation and
      cholesterol up-regulation as model indicators. We found that bile acid-induced
      PKCalpha activation is a function of hydrophobicity and correlated with
      alteration in membrane lipid composition, as evident by the significant up
      regulation in membrane cholesterol and phospholipid. We found that bile acid do
      not cause cell membrane disruption at a concentration sufficient to activate
      PKCalpha, but do induce drastic alterations in membrane composition. Bile acid
      also induced the modification and up-regulation of caveolin-1 in a hydrophobicity
      dependent manner, implying widespread receptor dysregulation. Similarly, ERK1/2
      activation was observed only in response to hydrophobic bile acids, suggesting
      hydrophobicity-induced caveolar or membrane stress. Experiments with sodium
      lauryl sarcosine and cholesteryl hemisuccinate showed that bile acid-induced
      membrane alterations can be mimicked by hydrophobic molecules unrelated to bile
      acids, strongly implicating hydrophobicity as an important determinant of bile
      acid signaling.

PMID- 15951238
TI  - Efflux of lipid from macrophages after induction of lipid accumulation by
      chylomicron remnants.
AB  - The fate of cholesterol and triacylglycerol taken up and accumulated by
      macrophages after exposure to chylomicron remnants was investigated using
      macrophages derived from the human monocyte cell line THP-1 and chylomicron
      remnant-like particles containing human apolipoprotein (apo) E (CRLPs) as the
      experimental model. In THP-1 macrophages lipid loaded with CRLPs and incubated
      with various cholesterol acceptors for 24 h, the mass of cholesterol and
      cholesteryl ester found in the cells was not changed by HDL, HDL3 or lipid-free
      ApoA-I, although it was decreased by 38% by ApoA-I-phosphatidylcholine vesicles
      (ApoA-I-PC). After loading of the macrophages with [3H]cholesterol-labelled
      CRLPs, only about 5% of the label was effluxed in 24 h in the absence of
      cholesterol acceptors, and this increased to about 10% with ApoA-I or PC only,
      and to about 30% with apoA-I-PC. In similar experiments with [3H]triolein, only
      about 4% of the labelled triacylglycerol taken up by the cells was released into
      the medium in 24 h, and a large (>60%) and consistent proportion of the
      intracellular radioactivity remained associated with the triacylglycerol
      throughout this period. These results suggest that cholesterol and
      triacylglycerol derived from chylomicron remnants are not readily cleared from
      macrophages, and this is likely to contribute to the atherogenicity of the
      remnant lipoproteins.

PMID- 15951239
TI  - Arming antibodies for cancer therapy.
AB  - Specifying the delivery of a highly toxic agent to cancers while sparing normal
      tissue is an attractive prospect for the treatment of cancer. Cell surface
      antigens with highly restricted expression patterns have been identified and the
      means by which cytotoxic agents are appended to antibodies has been greatly
      refined. Myriad formulations involving radionuclides, bacterial toxins and small
      molecule drugs linked to antibodies through peptides, protein fusions and
      chelating agents are in preclinical and clinical evaluation, and a few have been
      approved as human medicines. Recent advances hold promise for improving the
      therapeutic index of these anti-cancer drugs.

PMID- 15951240
TI  - Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral
      blood stem cells by leukapheresis.
AB  - The plasma levels of matrix metalloproteinase-9 (MMP-9) were determined during 41
      collections of peripheral blood stem cells (PBSC) by standard volume (two blood
      volumes) leukaphereses (SVL) in 29 donors (7 allogeneic and 22 autologous)
      mobilized with the granulocyte-colony stimulating factor (G-CSF). The association
      between MMP-9 levels and cell counts in donor's blood was explored. During the
      processing of the first blood volume (BV), MMP-9 levels declined on average by
      31% and persisted at the same level during the processing of the second BV.
      During the collection, a slight decline of white blood cells (WBC),
      polymorphonuclear neutrophils (PMN) and platelets (PLT) in donor's blood was
      accompanied by a significant drop of CD34+ cells by 37% after 1 BV and by 44%
      after 2 BV had been processed (p=0.001). The drop of MMP-9 plasma levels showed a
      loose correlation with the decrease of WBC (r=0.68, p=0.002) and PMN counts
      (r=0.67, p=0.001). We conclude that the levels of MMP-9 that have been elevated
      by the mobilization of donors with G-CSF, decrease during the collection of PBSC
      by 4h SVL. The observed decrease was indirectly related to the drop of WBC and
      PMN counts, suggesting that certain other factors have an influence on MMP-9
      kinetics during PBSC collection.

PMID- 15951241
TI  - Hemoglobin screening in prospective blood donors: comparison of different blood
      samples and different quantitative methods.
AB  - Portable photometers are increasingly used for hemoglobin screening in blood
      centers. In a total of 500 unselected prospective blood donors, venous hemoglobin
      concentrations were measured using a hematology analyzer, and fingerstick
      hemoglobin concentrations were measured on both a HemoCue B and a Biotest
      hemoglobin photometer. In 100 of the donors, earstick hemoglobin levels were also
      measured on the HemoCue system. The mean hemoglobin levels in the fingerstick
      samples were slightly higher than those in the venous samples. The deviation
      exceeded the limit of +/-10g l(-1) in 9% of samples tested by HemoCue and in 20%
      of those investigated by Biotest. The use of earstick samples led to considerable
      overestimation of the actual hemoglobin concentration.

PMID- 15951242
TI  - Usefulness of particle image analyzer for evaluation of fragmented red cells.
AB  - Quantitative determination of fragmented red cells (FRCs) in peripheral blood is
      useful in various clinical fields. We have previously reported an automatic
      detection method using a hematology analyzer essentially based on detection of
      small red cells. We then tried to use another instrument, the FPIA 2100, to
      reflect the characteristic morphology of red cells. As the circularity obtained
      by FPIA 2100 correlated with the FRC%, this type of instrument might be helpful
      to establish better automatic detection methods.

PMID- 15951243
TI  - The role of therapeutic plasma exchange in the catastrophic antiphospholipid
      syndrome.
AB  - The catastrophic antiphospholipid syndrome (CAPS) is a life-threatening sub
      entity of the antiphospholipid syndrome (APS) resulting in multiorgan failure and
      a mortality rate that may reach 50%. The optimal treatment regimen for CAPS is
      unknown. To evaluate the benefit of therapeutic plasma exchange (TPE) therapy in
      CAPS, we undertook a computer-assisted (MEDLINE, National Library of Medicine,
      Bethesda, MD) search of the literature to locate all cases of CAPS (case reports
      and reviews) treated with TPE. In view of the published literature so far, TPE
      has shown reasonable therapeutic benefits and improved survival for patients with
      CAPS. The use of this technique, along with anticoagulation and if needed
      pharmacological immunosuppression, should be considered for the acute management
      of patients who present with this life-threatening condition.

PMID- 15951244
TI  - Assessment of blinding may be inappropriate after the trial.

PMID- 15951246
TI  - Measurement of skin vasoconstrictor response in healthy subjects.
AB  - OBJECTIVES: Laser Doppler flowmetry enables non-invasive quantification of skin
      blood flow and its sympathetically mediated change. Four different maneuvers were
      performed in 60 healthy subjects aged 20-78 years to investigate their
      variability, reproducibility and to determine the influence of gender, age and
      height. MATERIAL AND METHODS: Skin blood flow was measured on the pulp of both
      index fingers using laser Doppler flowmetry. Vasoconstriction was induced by deep
      inspiratory gasp, arm dependency, acoustic stimulation and a modified cold
      pressor test. RESULTS: More than 95% of normal subjects showed a vasoconstrictor
      response to cold pressure test and 100% to inspiratory gasp. In all other
      maneuvers vasoconstrictor response was less reliable. The magnitude of
      vasoconstrictor responses decreased with age in all maneuvers, while latencies
      remained unchanged. Only during inspiratory gasp men showed more pronounced
      vasoconstrictor response compared with women. Body height influenced latencies if
      peripheral stimuli were applied like in the cold pressor and arm dependency
      tests. CONCLUSIONS: Inspiratory gasp and the modified cold pressor test were
      found to be more suitable maneuvers for routine clinical testing than arm
      dependency and acoustic stimulation. Normal data also for side differences are
      provided as a base for routine clinical testing in systemic and unilateral
      neurological disorders.

PMID- 15951245
TI  - The MEMA kwa Vijana project: design of a community randomised trial of an
      innovative adolescent sexual health intervention in rural Tanzania.
AB  - BACKGROUND: Effective interventions to reduce the incidence of HIV, other
      sexually transmitted infections (STIs) and unwanted pregnancy among adolescents
      in sub-Saharan Africa are urgently needed. This paper describes the rationale and
      design of a randomised trial of the impact of an innovative sexual health
      intervention among adolescents in rural Mwanza Region, Tanzania. METHODS: The
      MEMA kwa Vijana intervention comprises a teacher-led, peer-assisted sexual health
      education programme for students in the last 3 years of primary school, training
      and supervision of health workers in the provision of youth-friendly health
      services, peer condom promotion and distribution, and wider community activities.
      Detailed process evaluation was conducted and the impact of the intervention was
      evaluated through a community-randomised trial in which a cohort of 9645
      adolescents was followed up for 3 years. Both process and impact evaluation used
      multiple assessment methods. Impact measures included incidence and prevalence of
      HIV and other STIs, pregnancy rates, knowledge and reported attitudes and sexual
      behaviour, as well as qualitative assessments. RESULTS: Results of the baseline
      survey of the cohort have been presented previously. The outcome of the trial
      will be reported separately. CONCLUSIONS: Behaviour change interventions among
      adolescents have been widely advocated, but there have been few rigorously
      designed trials of their effectiveness, particularly in developing countries, and
      measurement of sexual behaviour is particularly problematic in this age group.
      The MEMA kwa Vijana trial was undertaken to address these problems and to collect
      rigorous evidence on the effectiveness of an innovative intervention, designed to
      be implemented on a very large scale.

PMID- 15951247
TI  - Characterization of an ecto-ATPase activity in Cryptococcus neoformans.
AB  - Cryptococcus neoformans is the causative agent of pulmonary cryptococcosis and
      cryptococcal meningoencephalitis, which are major clinical manifestations in
      immunosuppressed patients. In the present study, a surface ATPase (ecto-ATPase)
      was identified in C. neoformans yeast cells. Intact yeasts hydrolyzed adenosine
      5'-triphosphate (ATP) at a rate of 29.36+/-3.36nmol Pi/hx10(8) cells. In the
      presence of 5 mM MgCl(2), this activity was enhanced around 70 times, and an
      apparent K(m) for Mg-ATP corresponding to 0.61mM was determined. Inhibitors of
      phosphatases, mitochondrial Mg(2+)-ATPases, V-ATPases, Na(+)-ATPases or P-ATPases
      had no effect on the cryptococcal ATPase, but extracellular impermeant compounds
      reduced enzyme activity in living cells. ATP was the best substrate for the
      cryptococcal ecto-enzyme, but it also efficiently hydrolyzed inosine 5'
      triphosphate (ITP), cytidine 5'-triphosphate (CTP), guanosine 5'-triphosphate
      (GTP) and uridine-5'-triphosphate (UTP). In the presence of ATP, C. neoformans
      became less susceptible to the antifungal action of fluconazole. Our results are
      indicative of the occurrence of a C. neoformans ecto-ATPase that may have a role
      in fungal physiology.

PMID- 15951248
TI  - Design, preparation and testing of suitable probe-receptors for RNA biosensing.
AB  - Absolute measurements of a given RNA in a cheap, easy, rapid and reproducible
      manner using biosensors technology could overcome many of the operative and
      analytical limits of conventional molecular biology methods. To this end, an
      integrated approach for the design, synthesis, and connection of RNA probes to
      the transducing surface of a microgravimetric biosensor has been developed.
      Suitable probes to be used as the bioreceptors in RNA biosensor were successfully
      designed by using a purposely developed computational method whose selection
      criteria are based on the accessibility of target region to probe, on pairing
      stability of probe-target duplex and on the uniqueness of selected targets over
      all known expressed sequences from a genome data base. Automated chemical
      synthesis of selected probes was performed and the oligonucleotides produced were
      covalently conjugated to the sensing surface of a quartz microbalance. The
      microgravimetric sensor was tested in a flow chamber by measuring the variation
      of resonance frequency due to the binding of synthetic target substrates.
      Specific dose dependent binding was observed. Furthermore, the binding of a
      transcribed full-length mRNA substrate was successfully monitored under similar
      conditions.

PMID- 15951249
TI  - Influence of double-strand-break repair pathways on radiosensitivity throughout
      the cell cycle in CHO cells.
AB  - Unrepaired DNA double-strand breaks (DSBs) produced by ionizing radiation (IR)
      are a major determinant of cell killing. To determine the contribution of DNA
      repair pathways to the well-established cell cycle variation in IR sensitivity,
      we compared the radiosensitivity of wild-type CHO cells to mutant lines defective
      in nonhomologous end joining (NHEJ), homologous recombination repair (HRR), and
      the Fanconi anemia pathway. Cells were irradiated with IR doses that killed
      approximately 90% of each asynchronous population, separated into synchronous
      fractions by centrifugal elutriation, and assayed for survival (colony
      formation). Wild-type cells had lowest resistance in early G1 and highest
      resistance in S phase, followed by declining resistance as cells move into G2/M.
      In contrast, HR-defective cells (xrcc3 mutation) were most resistant in early G1
      and became progressively less resistant in S and G2/M, indicating that the S
      phase resistance in wild-type cells requires HRR. Cells defective in NHEJ (dna
      pk(cs) mutation) were exquisitely sensitive in early G1, most resistant in S
      phase, and then somewhat less resistant in G2/M. Fancg mutant cells had almost
      normal IR sensitivity and normal cell cycle dependence, suggesting that Fancg
      contributes modestly to survival and in a manner that is independent of cell
      cycle position.

PMID- 15951250
TI  - Perinatal development of respiratory motoneurons.
AB  - Breathing movements require the coordinated recruitment of cranial and spinal
      motoneurons innervating muscles of the upper airway and ribcage. A significant
      part of respiratory motoneuron development and maturation occurs prenatally to
      support the generation of fetal breathing movements in utero and sustained
      breathing at birth. Postnatally, motoneuron properties are further refined and
      match changes in the maturing respiratory musculoskeletal system. In this review,
      we outline developmental changes in key respiratory motoneuronal populations
      occurring from the time of motoneuron birth in the embryo through the postnatal
      period. We will also bring attention to major deficiencies in the current
      knowledge of perinatal respiratory motoneuron development. To date, our
      understanding of processes occurring during the prenatal period comes primarily
      from analysis of phrenic motoneurons (PMNs), whereas information about postnatal
      development derives largely from studies of PMN and hypoglossal motoneuron
      properties.

PMID- 15951251
TI  - Upper airways and neonatal respiration.
AB  - The upper airways exert an important influence on breathing from the fetal period
      onward. This review focuses on recent results obtained in the newborn,
      particularly on laryngeal function in the lamb. Cumulated data can be summarized
      as follows. Firstly, upper airway closure, either at the pharyngeal or laryngeal
      level, is now known to occur during central apneas. By maintaining a high apneic
      lung volume throughout central apneas, active laryngeal closure decreases the
      magnitude of post-apneic desaturation. Secondly, reflexes originating from
      laryngeal mucosal receptors, such as laryngeal chemoreflexes and non-nutritive
      swallowing, are of crucial importance within the context of preterm birth,
      postnatal maturation, neonatal apneas and apparent life-threatening events/sudden
      infant death syndrome. While laryngeal chemoreflexes appear to be mature and
      confer an efficient protection against aspiration in the full-term healthy
      newborn, they can be responsible for prolonged apneas and bradycardias in the
      immature preterm newborn. In regard to non-nutritive swallowing, the absence of
      swallowing activity during apneas in periodic breathing during quiet sleep as
      well as the presence of bursts of swallows with apneas in active sleep remain to
      be explained. Forthcoming studies will have to further delineate the impact of
      common clinical conditions, such as cigarette smoke exposure and/or viral
      respiratory infection on laryngeal chemoreflexes and non-nutritive swallowing.
      Better knowledge on the importance of the upper airways in neonatal respiration
      will ultimately aid in designing clinical applications for the understanding and
      treatment of severe, pathological respiratory conditions of the newborn.

PMID- 15951252
TI  - Imidazole binding reagent diethyl pyrocarbonate (DEPC) inhibits avian
      intrapulmonary chemoreceptor discharge in vivo.
AB  - Data indicate that avian intrapulmonary chemoreceptors (IPC) transduce CO2
      stimuli by sensing the products of CO2 hydration, [H+] and [HCO3-]. The alphastat
      regulation hypothesis of physiological pH sensitivity suggests that proteins
      sense [H+] through changes in the ionization state of imidazole groups (alphaIm).
      To test whether imidazole is involved with IPC CO2 sensitivity, we administered
      diethyl pyrocarbonate (DEPC) intravenously while recording from IPC exposed to
      varying levels of inspired CO2. At physiological pH, DEPC converts pH sensitive
      imidazole groups to pH-insensitive N-carbethoxyhistidyl residues. Single cell
      extracellular neural recordings were made from vagal filaments in anesthetized,
      unidirectionally ventilated Anas platyrhynchos. Without DEPC, IPC discharge rate
      was inversely proportional to inspired CO2 with characteristic dynamic responses
      to rapid CO2 alterations (n = 10). After DEPC treatment (> or = 15 mM), mean
      sensitivity of IPC discharge to static inspired CO2 levels was decreased 75% (P <
      0.05), and mean peak dynamic IPC discharge rate was decreased 80% (P < 0.05).
      Additionally, we tested whether DEPC might alter IPC discharge by binding
      imidazole groups in the enzyme carbonic anhydrase (CA), but we found no effect on
      CA catalytic rate. We conclude that DEPC inhibits IPC CO2 signal transduction by
      modifying imidazole groups on acid-sensitive proteins other than CA, possibly
      membrane acid-base exchangers or ion channels. These data support the alphastat
      regulation hypothesis in IPC CO2 respiratory chemoreception and suggests a more
      direct link between H+ and membrane excitability.

PMID- 15951253
TI  - Quantification by affinity perfusion chromatography of phosphorylated BRCAl and
      BRCA2 proteins from tumor cells after lycopene treatment.
AB  - A new procedure for the quantification of phosphorylated BRCA1 (P-BRCA1) and
      BRCA2 (P-BRCA2) proteins in breast cell lines after different treatments was
      carried out. Cells were cultivated with [35S]-methionine and extracts subjected
      to three perfusion chromatographies. First heparin affinity chromatography
      purified cellular DNA-binding proteins. Subsequent specific immunoprecipitation
      of BRCA1 and BRCA2 proteins was performed with antibodies raised against BRCA1 or
      BRCA2. The immune complexes were isolated by protein A affinity chromatography.
      Phosphorylated BRCA1 or BRCA2 proteins were then purified with a Poros 20 AL
      column where anti-phosphothreonine and anti-phosphoserine antibodies were
      previously bound. The percentage of phosphorylated BRCA1 or BRCA2 proteins was
      calculated as follows: 100 x dpm of P-BRCA1 or P-BRCA2 eluted from the POROS 20AL
      column/total dpm eluted from POROS 20AL column. Treatment with 10 microM lycopene
      increased P-BRCA1 and P-BRCA2 in the breast tumor cell line MCF7 but not in MDA
      MB-231 or MCF-10a, breast tumor or fibrocystic cell lines, respectively.

PMID- 15951254
TI  - Crystallization and preliminary X-ray crystallographic analysis of extracellular
      giant hemoglobin from pogonophoran Oligobrachia mashikoi.
AB  - An extracellular giant hemoglobin of Oligobrachia mashikoi, composed of 24
      globins with the molecular mass of approximately 400 kDa was crystallized in its
      intact form. Two crystal forms were obtained by the vapor-diffusion method. Form
      I crystals obtained using sodium acetate as a precipitant belong to the space
      group P6(1)22 or P6(5)22, with unit-cell parameters a=112.41, c=621.25 A, and
      diffracted X-rays beyond 3.0 A resolution. Form II crystals obtained using PEG
      10000 as a precipitant belong to the space group R32, with unit-cell parameters
      a=111.50, c=276.84 A, and diffracted X-rays beyond 2.9 A resolution. The crystals
      are suitable for X-ray crystallography to determine the supramacromolecular
      assembly of this giant hemoglobin.

PMID- 15951255
TI  - Liver enzyme values in injection drug users with chronic hepatitis C.
AB  - BACKGROUND: Liver enzymes fluctuate in chronic hepatitis C virus infection.
      However, the range that can be attributed to the course of hepatitis C virus
      (versus an intercurrent cause of hepatitis) is unknown. AIMS: To characterise the
      range of liver enzyme values as a function of the upper limit of normal (ULN) of
      the assay among persons chronically infected with hepatitis C virus. PATIENTS:
      One thousand and fifty-nine hepatitis C virus chronically infected individuals
      with > or =5 semi-annual evaluations. METHODS: Alanine aminotransferase and
      aspartate aminotransferase levels were prospectively obtained. Potential causes
      of elevations were examined using serologic testing. RESULTS: Among 1059
      individuals, 11,463 enzyme measurements were obtained over 6.5 years, of which
      63.5% were <1.25x ULN, 26.5% were 1.25-2.5x ULN, 8.3% were 2.5-5x ULN, and 1.6%
      were 5-10x ULN; only 0.2% were >10x ULN. Elevations >10x ULN were transient, the
      alanine aminotransferase/aspartate aminotransferase ratio tended to be different
      at the time of the elevation compared to before and after and 24% were associated
      with acute viral hepatitis. On the other hand, subjects with elevations 5-10x ULN
      tended to have elevated levels throughout follow-up and only 8% were associated
      with acute viral hepatitis. CONCLUSIONS: Liver enzymes fluctuate up to 5x ULN in
      most hepatitis C virus-infected persons; clinicians should seek alternate
      explanations for those with higher alanine aminotransferase or aspartate
      aminotransferase levels, especially among hepatitis C virus-infected persons with
      greater than 10-fold elevations.

PMID- 15951257
TI  - [Prescription, assay and interpretation of cardiac troponins tests: guidelines
      from SFBC-CNBC troponin working group].
AB  - Troponin (I or T) has become the gold-standard marker in acute coronary syndromes
      during the last few years, as confirmed by a national survey realized within
      french clinical chemists, cardiologists and emergency practitioners. The
      importance of this marker and the heterogeneousness of circulating forms of
      troponin after myocardial necrosis fully justify international studies about
      standardization of this assay, which is a central bulk to reach a global market
      coherence. Checking analytical problems, although necessary, must be absolutely
      associated with an informed clinical interpretation. The knowledge of the crucial
      thresholds of each assay, the kinetic curves and the specificity limits of
      troponin assays allow the best use of their potential in diagnosis and prognosis
      together with an optimal patient care in very different clinical settings, in
      addition to others clinical and technical arguments. The quality improvement
      through successive generations of assay kits must nowadays persuade the
      physicians never to ignore a significant and valid troponin increase, which
      mainly reveals a cardiac injury, whatever its origin.

PMID- 15951258
TI  - [Dicentric Y chromosomes. First part: cytogenetic and molecular aspects].
AB  - Dicentric Y chromosomes have been reviewed twice in 1994 by Hsu et al. and in
      1995 by Tuck-Muller et al. who showed that dic(Y) are the most common Y
      structural abnormalities and that their influence on gonadal and somatic
      development is extremely variable. The prediction of their phenotypic
      consequences is often difficult because of the variety of genomic sequences
      concerned by duplications and deletions, because of the variable degrees of
      mosaicism (cell line 45,X in particular) and at the end, because of
      identification and analysis technical difficulties of the structure of the
      rearranged Y chromosome. The clinical specter of this cytogenetic abnormality is
      rather wide going from almost-normal or infertile males, to females with or
      without stigmas of Turner syndrome. Middle phenotypes consist of various degrees
      of genital ambiguities. However, clinical expression seems to be related to the
      genomic capital of the Y chromosome, mainly the Y genes involved in the control
      of the process of the determination of gonads (Yp) and spermatogenesis (Yq) as
      well as control of the growth and the skeletal development (Yp). Here, we report
      a third comprehensive review of the literature concerning dicentric Y chromosomes
      reported since 1994. In the light of previous reviews as well as the recent data
      of the genetic cartography of the Y chromosome, we try, in this first part, to
      determine characteristics of reported dicentric Y chromosomes as well as their
      chromosomal mechanics, their mitotic stability and finally their cytogenetic and
      molecular investigations.

PMID- 15951259
TI  - [Reproductibility of the morphological identification of schisocytes and
      evaluation of non observer-dependent methods].
AB  - Schistocytes are red blood cell fragments observed on a blood smear. They are a
      mark of mechanical haemolytic anaemias whose group of the thrombotic micro
      angiopathies requires an urgent treatment. The detection of the schistocytes and
      sometimes their quantification are thus of primary importance. To evaluate this
      search for schistocytes, several surveys of practice were carried out (1999-2003)
      including pictures of blood fields (identification of schistocytes among abnormal
      red blood cells) near biologists of variable level of specialization. The aim was
      to try to lead to a consensus, in particular for the morphological criterias of
      identification. Our results indicated that: 1) the biologists are badly
      sensitized with the importance of this research and the consequences of their
      response for the diagnosis; 2) the morphological identification of the
      schistocytes is difficult with an important variability of the criteria according
      to the observers. An investigation overviewed by the French Group of Cellular
      Hematology (Delphi method) allowed the development of a morphological consensus
      (fragments of triangular/crescent/helmet forms with rectilinear zone testifying
      to the zone of break). In order to cancel the observer-dependent identification
      of the schistocytes, a software of morphometric analysis (Q-WIN, Leica) was
      developed for sorting, starting from digitalized microscopic fields, the
      fragmented - among the normal - red blood cells. The results appeared
      encouraging, but not yet optimized. An automated analyzer (Bayer ADVIA 120) was
      also evaluated for the measurement of the schizocytes ("fragmented red blood
      cells" parameter). The moderate over-estimation of the real schizocytes (+ 0,4%)
      encouraged to observe the clinical value of the fragmented red blood cells
      detection in a group of patients that undergone a bone-marrow transplantation.
      The predictive value of the test (98%) was satisfactory.

PMID- 15951260
TI  - [Protein profile and vitamin A in children of school age in Ivory Coast].
AB  - The purpose of this transverse prospective study was to determine blood
      nutritional, immunity and inflammatory proteins change in vitamin A deficiency in
      children of school-age (262 children, aged 7 to 15 years). Blood vitamin A has
      been determined by HPLC with UV detection. Proteins have been measured by radial
      immunodiffusion according to Mancini. Results showed that 96 children (36.6%)
      presented a vitamin A deficiency (vitamin A < 200 microg/L with a retinol binding
      protein/transthyretin molar ratio = 0.29 +/- 0.06) while 166 (63.3%) children
      presented normal blood concentrations of vitamin A (vitamin A > or = 200 microg/L
      with a Retinol Binding Protein/Transthyretin molar ratio = 0.40 +/- 0.08). This
      study showed that the retinol binding protein and the immunoglobulin A are lower
      in children with vitamin A deficiency. On the other hand, an isolated increase of
      alpha-1 glycoprotein acid has been observed in boys with vitamin A deficiency.
      The vitamin A deficiency observed in this survey is due to a micronutrients
      deficiency in the diet which is essentially based on glucides. The positive
      correlation between vitamin A and immunoglobulin A concentrations might be the
      result of the vitamin A inductive effect during immunoglobulins A synthesis. The
      isolated increasing of alpha-1 glycoprotein acid in boys with vitamin A
      deficiency has been assigned to the ecosensitiveness of the unfavourable
      environment. We therefore concluded that, in Ivorian primary-school-aged children
      with vitamin A deficiency, nutritional, immunity and inflammatory proteins which
      are modified are respectively retinol binding protein, immunoglobulin A and alpha
      1 glycoprotein acid.

PMID- 15951261
TI  - [Determination of urinary citrates by an alternative of Millan's method].
AB  - INTRODUCTION: the physiopathological interest of the determination of urinary
      citrate lies primarily in its relationships to the lithiasic processes. Indeed,
      the citrate is a powerful complexing agent of calcium able to lower urinary
      supersaturation of oxalate and phosphate of calcium. OBJECTS: this study
      describes a revaluation of the determination of urinary citrates by the
      colorimetric method of Millan. METHODS: the principle of the method rests on the
      quantification of the yellow complex formed with iron chloride III and the
      urinary citric acid, measurable at 390 nm in acidic medium. All the conditions
      were combined to optimize it, while covering a satisfying field of measurement.
      RESULTS AND COMMENTS: the evaluation of the modified method showed a good
      precision (repeatability: CV from 0,18 to 3,42%; intraserial reproducibility: CV
      from 1,87 to 3,44 %; interserial reproducibility: CV from 2,15 to 5,52%) and a
      very good accuracy. The field of measurement extends up to 17,0 mmol/L, with a
      limit of detection (L(D)) lowered to 0,2 mmol/L (Vs 1,48 mol/L for the original
      method). All analytical performances are improved by automation with a L(D) =
      0,09 mmol/L and a limit of linearity extended to 18 mmol/L. CONCLUSION: this
      modified, simple, fast, inexpensive and easily automatizable technique, seems to
      be reliable and especially more sensitive, adapting particularly to the detection
      of subjects suffering a deficit of citrate secretion, one of most significant
      inhibiting agent of lithiasis kidney formation.

PMID- 15951262
TI  - [Results transferability on RXL, ARX, X-Pand, BN2 (Dade Behring) and modular DP
      (Roche Diagnostics) analysers: application to component assays of fibrotest and
      Actitest].
AB  - The follow up of patients with chronic liver diseases and the data from
      multicentric clinical studies are affected by the variability of assay results
      for the same parameter between the different laboratories. Today, the main
      objective in clinical chemistry throughout the world is to harmonise the assay
      results between the laboratories after the confirmation of their traceability, in
      relation to defined reference systems. In this context, the purpose of our study
      was to verify the homogeneity of haptoglobin, apolipoprotein A1, total bilirubin,
      GGT activity, ALAT activity results, which are combined in Fibrotest and
      Actitest, between Dimension Analysers RXL, ARX and X-PAND (Dade Behring Society).
      Moreover, we verified the transferability of Fibrotest and Actitest results
      between the RXL, and either the BN2 (haptoglobin and apolipoprotein A1) or the
      Modular DP (total bilirubin, GGT and ALAT activity concentrations). The serum
      samples from 150 hospitalised patients were analysed on the different analysers.
      Specific protein assays were calibrated using solutions standardised against
      reference material on Dimension and BN2 analysers. Total bilirubin assays were
      performed by a diazoreaction on Dimension and Modular DP analysers. The GGT and
      ALAT activity measurements on the Dimension analysers were performed in
      accordance with the reference methods defined by the International Federation of
      Clinical Chemisty and Laboratory Medicine (IFCC). On the Modular, enzyme activity
      measurements were performed according to the Szasz method (L-gamma- glutamyl-4
      nitroanilide as substrate) modified by Persijn and van der Slik (L-gamma-
      glutamyl-3-carboxy- 4-nitroanilide as substrat) for GGT and according to the IFCC
      specifications for ALAT. The methods of enzymatic activity measurement were
      calibrated on the Modular only. Liver fibrosis and necroinflammatory activity
      indices were determined using calculation algorithms, after having adjusted each
      component's result of Fibrotest and Actitest for gender and age. Our study has
      shown, for each parameter, harmonious results between the Dimension analysers and
      between RXL and BN2- Modular DP. Disregarding alpha-2 macroglobulin which cannot
      be assayed on RXL, the results of Fibrotest and Actitest were similar as
      performed on BN2- Modular DP and RXL.

PMID- 15951263
TI  - [Congenital methemoglobinemia: a rare case of cyanosis in the newborn].
AB  - We report the case of a newborn presenting a cyanosis after the birth with a good
      general state. Congenital methemoglobinemia is a rare disease which is
      characterized by a brutal appearance, in early infancy, of a bluish skin color
      not regressing with oxygen inspiration, and by a good general state. It is due to
      the recessive autosomal NADH-cytochrome b5 reductase (EC. 1.6.2.2) deficiency.
      This enzyme normally allows the reduction of the physiologically formed
      methemoglobinemia. Two forms of congenital methemoglobinemia have to be
      distinguished: the benign form (type I) and the severe form (type II).

PMID- 15951264
TI  - [Idiopathic hypereosinophilic syndrome: toward a new molecular-targeted therapy
      and a new cytomorphological and molecular definition].
AB  - Idiopathic hypereosinophilic syndrome is characterised by chronic
      hypereosinophilia leading to tissue damage, and after exclusion of reactive
      eosinophilia. Until recently no specific or efficient therapeutic was available.
      In 2003, a recurrent interstitial deletion 4q12 leading to the fusion of the
      FIP1L1 and PDGFRA genes was detected in hypereosinophilic syndromes. The
      resulting protein has constitutive tyrosine kinase activity which explains
      clinical and cytological remission of hypereosinophilic syndrome after treatment
      by a specific tyrosine kinase inhibitor, imatinib mesylate or Glivec, usually
      used in chronic myeloid leukaemia. Here we report a patient with
      hypereosinophilic syndrome associated to peculiar morphology of neutrophilic
      series and the 4q12 deletion. He presented clinical and haematological remission
      since the introduction of imatinib mesylate therapy.

PMID- 15951265
TI  - [Misinterpretation of measured bicarbonates during the administration of high
      doses of propofol].
AB  - A patient, admitted to intensive care unit and sedated with propofol (Diprivan),
      had repeatedly presented severe decreased of measured bicarbonates without
      metabolic acidosis and with physiologic values of calculated bicarbonates.
      Consecutively to the administration of high doses of propofol, an important
      lactescence of samples had been observed and the tests realised showed that
      lactescence play a key role in the interference with the measurement of
      bicarbonates (as described in the literature). So, in the course of propofol
      administration, it would be advised to interpret with caution the results of
      measured bicarbonates to not conclude too quickly on a case of "propofol
      syndrome".

PMID- 15951266
TI  - [A very high level in a cardiac troponin I assay].
AB  - Cardiac troponin I (TnIc) is a very sensitive and also a specific marker of
      myocardial injuries. We report here, the clinical case of a patient with a
      particularly important and brutal increase of the troponin during a myocardial
      infarction. A 64-year-old man was admitted to hospital. He had a myocardial
      infarction associated to a cardiac necrosis and important cytolysis. The troponin
      assay was normal when the patient was hospitalized. The angioplasty coronary
      reperfusion brought about a massive troponin Ic release in systemic circulation:
      the assay made 10 hours after the appearance of the symptoms shows us an
      exceptional TnIc concentration that is greater than 4000 microg/L (baseline: 1,5
      microg/L). This might be the highest value ever reported.

PMID- 15951268
TI  - [A case of alcohol-induced ketoacidosis?].
AB  - We report a case of severe ketoacidosis. Initially the patient showed metabolic
      acidosis, the anion gap was positive and there was neither hyperlactatemia nor
      intoxication with acid substances. As the rate of glycemia was high (17.8
      mmol/L), the diagnosis of diabetic ketoacidosis was proposed. Under treatment
      with continuous IV injection of insulin, hypoglycemia (1.8 mmol/L) appeared
      rapidly, while urine bioreactive test was positive for ketonuria, but negative
      for glycosuria. We finally concluded that it was an alcoholic ketoacidosis. The
      history of the patient confirmed the diagnosis : chronic alcoholism with recent
      increased of alcohol intake which provoked vomiting and fasting. This case report
      shows the difficulty in distinguishing between alcoholic ketoacidosis and
      diabetic ketoacidosis. We discuss the diagnostic strategy and particularly
      biologic data in the light of pathophysiologic mechanism of alcoholic
      ketoacidosis.

PMID- 15951267
TI  - [Acute organophosphorus pesticide poisoning and cholinesterases activities].
AB  - Suicides attempts with an organophosphate pesticide still occur in Brittany, an
      agricultural French area. The acute poisoning due to this nerve agent,
      responsible for the inhibition of the cholinesterases enzymes, is severe and can
      be fatal. The diagnosis is based on the decrease of cholinesterases activity, an
      assay which has been performed because of the patient context. The measurement of
      butyrylcholinesterases activity in emergency guarantees an appropriate and rapid
      management of the patient in order to rapidly regenerate cholinesterases. Even if
      the decrease level of butyrylcholinesterases activity does not give a significant
      prognostic value, its follow-up with time indicates the efficacy of the treatment
      and the gradual remission. In routine the measurement of acetylcholinesterase
      activity is more useful for the biological follow-up of subjects exposed to
      organophosphate phytosanitary compounds.

PMID- 15951269
TI  - [HS CRP with Fumouze immunoturbidimetry and Dade Behring immunonephelemetry].
AB  - Increased concentrations of high sensitivity C-reactive protein are associated
      with increased risk for coronary heart disease. We report here a comparison of
      Fumouze hs-CRP turbidimetric method on Roche Diagnostics Hitachi 911 with Dade
      Behring BN II nephelemetric method. 134 samples were analysed. Within-run
      imprecision and between-run CV were good. Linearity was less satisfactory.
      Correlation study showed that without exceeding the maximum value of 6 mg/L, the
      hs-CRP method presented a good agreement with hs-CRP BN II method.

PMID- 15951270
TI  - [Digoxin assay: results of 10 years of intralaboratory controls].
AB  - Serum digoxin measurement is often performed in medical laboratories. A
      professional association specialized in quality control, based in Lyon, has been
      organizing punctual controls of medication measurement for the past ten years.
      The results are analysed in term of intra and inter-technique precision,
      difference between methods and specificity in regard to endogenous or exogenous
      interfering substances. Methods have changed with a quasi disappearance of the
      methods used ten years ago (FPIA, EMIT) and introduction of new technologies on
      recent immunoanalysis automates. The results observed with the different
      instruments are similar. Reproductibility has not changed over ten years. Some
      difficulties remain in the measurement of low concentrations of digoxin. Many
      substances interfere in digoxin measurement : digoxigenine (inactive metabolite),
      endogenous digoxin-like immunoreactive factors, spironolacton, antidigoxin
      antibodies used for treatment of digitalic intoxications. These interferences
      depend on the method which is used, but it is essential to know them in order to
      interpret the results correctly.

PMID- 15951283
TI  - Hereditary hemorrhagic telangiectasia.

PMID- 15951285
TI  - Multipotential hematopoietic progenitor cells from embryos developed in vitro
      engraft unconditioned W41/W41 neonatal miceB.
AB  - BACKGROUND AND OBJECTIVES: The first hematopoietic stem cells (HSC) in the mouse
      able to give rise to the adult hematopoietic system emerge at embryonic day (E)
      10.5 in the intraembryonic aorta-gonads-mesonephros (AGM) region, as demonstrated
      by transplantation into irradiated adult recipients. It has been shown by
      transplantation into conditioned neonatal or hematopoietic mutant adult
      recipients that less potent multipotential hematopoietic progenitors exist in the
      mouse embryo at E9, one day earlier than the appearance of HSC. Studies of the
      lineage relationships of multipotential hematopoietic progenitors and HSC in the
      mouse embryo have been complicated by inaccessibility due to in utero
      development. Attempts are being made to create an in vitro whole mouse embryo
      culture system to access the developing mouse embryo for such studies of
      hematopoietic cell emergence during early and mid-gestational stages. The aim of
      this study was to compare the development of multipotential hematopoietic
      progenitors in early in utero and in vitro-developed mouse embryos. DESIGN AND
      METHODS: To test hematopoietic progentior/stem cell activity in the mouse
      embryonic tissues obtained from genetically marked in utero and in vitro
      developed embryos, transplantations were performed using unconditioned neonatal
      W41/W41 (c-kit hematopoietic mutant) recipients. Long-term donor-cell
      reconstitution in transplanted mice was measured by (i) semiquantitative
      polymerase chain reaction and (ii) flow cytometry on peripheral blood and
      hematopoietic organs. RESULTS: Our experimental data show that multipotent
      hematopoietic progenitors from in utero-developed embryos engraft unconditioned
      W41/W41 neonates. Furthermore, in vitro-developed whole embryos also contain
      early multipotent hematopoietic progenitor cells that are able to yield high
      level, long-term engraftment of W41/W41 neonates. INTERPRETATION AND CONCLUSIONS:
      The in vitro culture of whole mouse embryos during mid-gestational stages allows
      for the normal growth of multipotential hematopoietic progenitors that can be
      assayed by transplantation into W41/W41 neonatal recipients. Thus, in vitro
      developed whole embryos can be used with confidence in future studies to examine
      the lineage relationships of multipotential hematopoietic progenitors and HSC.

PMID- 15951286
TI  - Numerous erythroblasts in maternal blood are impervious to fluorescent in situ
      hybridization analysis, a feature related to a dense compact nucleus with
      apoptotic character.
AB  - BACKGROUND AND OBJECTIVES: The analysis by fluorescence in situ hybridization
      (FISH) of fetal erythroblasts enriched from maternal blood remains an attractive
      alternative for risk-free prenatal diagnosis of aneuploidies. However, current
      results are discouraging because of the low levels of sensitivity or the
      inability to detect fetal erythroblasts by FISH. DESIGN AND METHODS:
      Erythroblasts were enriched from 35 maternal blood samples by magnetic cell
      sorting (MACS), identified morphologically following May-Grunwald Giemsa staining
      and examined by FISH for chromosomes X, Y and 18. RESULTS: We observed that
      circulating erythroblasts comprised two distinct groups: one was clearly of
      maternal origin and could be reliably analyzed by FISH, whereas the other, which
      appeared to be of fetal origin, was largely impervious to FISH analysis. This
      latter feature seemed to be related to an abnormally dense nucleus with an
      apoptotic character. Since the oxygen tension in the maternal circulation is
      higher than that in the fetus, we cultured fetal cord blood erythroblasts in
      conditions mimicking this difference in oxygen concentrations and found that high
      oxygen concentrations rapidly induced shrinkage of the erythroblast nucleus,
      rendering it impervious to FISH analysis. INTERPRETATION AND CONCLUSIONS: Our
      data show that circulating erythroblasts of presumed fetal origin cannot be
      reliably analyzed by FISH because of an abnormally dense nucleus. This nuclear
      phenotype appears to be induced by the higher oxygen tension present in the
      maternal circulation than in fetal blood.

PMID- 15951287
TI  - Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence
      in situ hybridization.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to determine the incidence
      of rearrangements of NUP98 (the gene coding for nucleoporin 98kDa protein) in
      childhood acute myeloid leukemia (AML) and selected patients with 11p13-15
      rearrangements. This aim was achieved using a fluorescence in situ hybridization
      (FISH) assay that allows the detection of NUP98 aberrations independently of the
      partner gene involved. DESIGN AND METHODS: Screening of 59 consecutive patients
      enrolled in the Austrian AML-BFM93 clinical trial was performed by dual-color
      FISH. In addition, 14 selected cases with various hematologic malignancies and
      11p13-15 aberrations were analyzed. NUP98-positive cases were further
      investigated by fusion gene-specific FISH and reverse transcription polymerase
      chain reaction assays. RESULTS: Among the 59 AML patients, one NUP98-NSD1
      positive case (1.7%) was detected. Among the 14 selected patients, five new NUP98
      positive cases were determined. Two cases showed an inv(11)(p15q22)/NUP98-DDX10
      fusion, one each displayed a t(5;11)(q35;p15)/NUP98-NSD1 and a
      t(11;20)(p15;q12)/NUP98-TOP1 fusion, and one case with a putative new fusion
      partner gene at 3p24 was identified. INTERPRETATION AND CONCLUSIONS: The observed
      frequency of 1.7% confirmed the low incidence of NUP98 rearrangements in
      childhood AML. The low occurrence of NUP98 rearrangements in selected samples
      with 11p13-15 alterations suggests the existence of variable chromosomal
      breakpoints and affected genes in this region. The identification of a new NUP98
      fusion partner region confirms the evident promiscuity of NUP98. Thus, analysis
      of NUP98 aberrations by FISH seems to be the method of choice for determining the
      presence of these genetic lesions in unselected patients, and to confirm the
      involvement of NUP98 in cases with 11p15 aberrations.

PMID- 15951288
TI  - 6q- is an early and persistent chromosomal aberration in CD3-CD4+ T-cell clones
      associated with the lymphocytic variant of hypereosinophilic syndrome.
AB  - BACKGROUND AND OBJECTIVES: The lymphocytic variant of hypereosinophilic syndrome
      (LV-HES) is an underrated disease defined by the monoclonal proliferation of
      interleukin-5 secreting T-cells. This disease is distinguished by a period of
      chronic lymphoproliferation without clinical transformation, which is frequently
      a precursor to T-cell lymphoma. In this study, LV-HES was used as a model of pre
      malignancy to identify specific marker(s) predictive of the potential for
      malignant transformation. DESIGN AND METHODS: The karyotypic abnormalities
      detected in the abnormal CD3-CD4+ T cells were further characterized by
      fluorescent in situ hybridization. A multi-step retrospective analysis was
      performed on successive blood samples during a six-year follow up to correlate
      the evolution of cytogenetic changes with clinical progression. Expression array
      analysis was used to investigate the effect of these chromosomal aberrations on
      gene expression. RESULTS: A 6q deletion was detected in the two LV-HES patients
      during their chronic disease phase. An additional 10p deletion was found alone or
      in association with the 6q defect in one patient prior to the development of a
      CD3-CD4+ T-cell lymphoma six years after diagnosis. We show that the 6q but not
      the 10p deletion is both stable and persistent throughout the chronic disease,
      finally emerging as the predominant aberration in the lymphoma cells. Six genes
      mapped to the 6q-deleted region displayed altered gene expression profiles both
      in the chronic and malignant disease phases. INTERPRETATION AND CONCLUSIONS: Our
      data suggest that the 6q deletion represents an early cytogenetic marker for T
      cell transformation.

PMID- 15951289
TI  - A new human acute monocytic leukemia cell line SHI-1 with t(6;11)(q27;q23), p53
      gene alterations and high tumorigenicity in nude mice.
AB  - BACKGROUND AND OBJECTIVES: Human leukemia cell lines are of great value in
      leukemia research. Thus far 36 leukemia cell lines carrying the 11q23
      translocation and MLL rearrangements, including two cell lines with
      t(6;11)(q27;q23) and an MLL-AF6 fusion gene have been described. We have
      established a new monocytic cell line with t(6;11), designated SHI-1, and herein
      describe its biological characteristics. DESIGN AND METHODS: Mononuclear cells
      isolated from the bone marrow of a patient with acute monocytic leukemia (AML
      M5b) at relapse were inoculated and passaged by liquid culture. The biological
      features of the cell line were characterized by morphological assays, flow
      cytometry, cytogenetic analysis, reverse transcription polymerase chain reaction
      (RT-PCR), direct sequencing, fluorescence in situ hybridization (FISH),
      clonogenic culture, quantitative fluorescent PCR, zymography, short tandem
      repeating sequences-PCR (STR-PCR), multiplex-FISH (M-FISH), and tumorigenic
      capacity in nude mice. RESULTS: The SHI-1 cell line has been maintained in
      continuous culture without any external cytokines for three years. The morphology
      and immunoprofile of the cells show typical features of monocytic lineage.
      Karyotypic analysis demonstrated a t(6;11)(q27;q23) translocation accompanied by
      a deletion of 17p, which are the same abnormalities as were seen in the leukemia
      cells of this patient in relapse. The MLL-AF6 fusion transcript and the loss of
      one p53 allele were proven by chromosome painting, FISH and RT-PCR analysis in
      both SHI-1 cells and the primary leukemia cells. A point mutation of ATC-->ACC at
      codon 195 of exon 6 in another p53 allele was found by direct sequencing of DNA
      in SHI-1 cells as well as in the primary leukemia cells. Neither Epstein-Barr
      virus nor mycoplasma was detected in SHI-1 cells. Tumor masses were found in all
      sixteen mice 9-19 days after subcutaneous injection of SHI-1 cells. DNA
      fingerprinting confirmed the authenticity of the cell line. INTERPRETATION AND
      CONCLUSIONS: SHI-1 is a new monocytic leukemia cell line with the t(6;11)
      translocation, p53 gene alterations, and high tumorigenicity in nude mice. It
      could be a valuable tool in the study of leukemogenesis.

PMID- 15951290
TI  - Fludarabine and cytarabine as continuous sequential infusion for elderly patients
      with acute myeloid leukemia.
AB  - BACKGROUND AND OBJECTIVES: A phase II study was conducted to investigate the
      effects of a therapeutic program based on the combination of fludarabine and
      cytarabine (ARA-C) administered as a sequential continuous infusion in untreated
      elderly patients with acute myeloid leukemia (AML). DESIGN AND METHODS: Sixty
      three patients with non-M3 AML, median age 69 years (range 61-81), were accrued.
      Twenty-four patients (38%) had AML secondary to myelodysplastic syndrome.
      Fludarabine and ARA-C were administered as a continuous sequential infusion for
      72 and 96 hours, respectively, after a loading dose. Patients achieving complete
      remission (CR) were intended to receive an additional course, followed by
      autologous stem cell transplantation (ASCT). RESULTS: Overall, 42 patients (67%)
      achieved CR. There were 10 induction deaths (16%), while 11 patients were
      refractory (17%). Among those achieving a remission, 35 patients (83%) received
      the planned consolidation course and 29 underwent mobilization of CD34+ cells
      into the peripheral blood for collection, which was successful in 23 (79%).
      Overall, 17 patients (27% of the whole population) received ASCT. The median
      overall and disease-free survival were both 10 months. INTERPRETATION AND
      CONCLUSIONS: Patients with an intermediate karyotype and those receiving ASCT had
      a significantly better clinical outcome. Results in terms of CR achievement,
      CD34+ cell collection and ASCT feasibility. A longer follow up is needed in order
      to evaluate the actual benefit on long-term survival.

PMID- 15951291
TI  - Expansion of natural killer cells with lytic activity against autologous blasts
      from adult and pediatric acute lymphoid leukemia patients in complete hematologic
      remission.
AB  - BACKGROUND AND OBJECTIVES: Natural killer (NK) cells constitute an important area
      of research for hematologic malignancies. The anti-leukemic activity of NK cells
      against acute myeloid leukemia (AML) blasts has been described, but very few data
      are available for acute lymphoid leukemia (ALL). The present study was designed
      to investigate whether: (i) NK effectors could be expanded from adult and
      pediatric ALL patients in complete remission; (ii) the signal transduction
      machinery of these cells was preserved; (iii) NK cells showed cytotoxic activity
      against autologous blasts; (iv) interleukin (IL)-2, IL-12 and IL-15 were able to
      increase lytic activity in our in vitro model; (v) any differences in cytotoxic
      activity could be found between expanded effectors from adult and pediatric
      patients. DESIGN AND METHODS: We co-cultured patients' peripheral blood
      mononuclear cells (PBMC) with the feeder cell line RPMI 8866 and analyzed the NK
      cells' expansion capacity by cell count and cytofluorimetric analyses. Signal
      transduction of expanded effector cells was evaluated by Western blot. 51Cr
      release assays, before and after stimulation with activating cytokines, were
      performed to analyze the cytotoxic potential of effector cells against tumor cell
      lines and autologous blast cells. Data were analyzed with t-tests for paired
      data. RESULTS: We obtained an average 40-fold increase in NK cells. Signal
      transduction through the CD16 receptor was preserved. Patients' expanded cells
      showed cytotoxic activity against target cell lines comparable to that of normal
      donors. More significantly, these cells also exerted a lytic effect against
      autologous blasts. In addition, incubating these effectors for 24 hours with IL-2
      + IL-15 significantly increased this cytotoxic function. No differences in
      expansion and cytotoxic activity were found between pediatric and adult patients.
      INTERPRETATION AND CONCLUSIONS: These findings document for the first time the
      possibility of expanding ex vivo cytotoxic effectors with autologous killing
      capacity from ALL patients in remission, and suggest a new potential
      immunotherapeutic strategy for the management of early disease recurrence or of
      residual disease.

PMID- 15951292
TI  - High dose sequential chemotherapy with autologous transplantation versus dose
      dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse
      large cell lymphoma: an "Intergruppo Italiano Linfomi" randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Poor prognosis diffuse large cell lymphoma (DLCL)
      responds poorly to standard chemotherapy. Randomized studies comparing high-dose
      chemotherapy with autologous stem-cell transplantation (ASCT) against standard
      chemotherapy have produced conflicting results. Dose-dense chemotherapy with
      granulocyte colony-stimulating factor (G-CSF) support seems to hold promise. The
      purpose of this multicenter, randomized trial was to compare failure-free and
      overall survival in patients with poor prognosis DLCL treated with high-dose
      sequential (HDS) chemotherapy followed by ASCT or an outpatient dose-dense
      chemotherapy regimen (MegaCEOP). DESIGN AND METHODS: Between 1996 and 2001, 130
      DLCL patients, aged < or = 60 years, with intermediate-high or high-risk disease,
      according to the International Prognostic Index score, and/or bone marrow
      involvement were enrolled. Sixty were randomized to HDS chemotherapy plus high
      dose mitoxantrone and melphalan with ASCT (arm A) and 66 to the MegaCEOP regimen
      (6-8 courses of an escalated dose of cyclophosphamide and epirubicin plus
      vincristine and prednisone with G-CSF every 2-weeks) (arm B); 4 patients were
      considered ineligible. RESULTS: The complete remission rate was 59% in arm A and
      70% in arm B (p = 0.18). After a median follow-up of 78 months, the 6-year
      failure-free survival was 45% in arm A and 48% in arm B (hazard ratio = 1.15, 95%
      confidence intervals = 0.72-1.84, p = 0.56). The 5-year overall survival was 49%
      in arm A and 63% in arm B (hazard ratio = 1.67, 95% confidence interval = 0.98
      2.85, p = 0.06). Two cases of secondary acute myeloid leukemia were observed
      after treatment in group A. INTERPRETATION AND CONCLUSIONS: HDS and ASCT as
      initial therapy for patients with poor-prognosis DLCL does not provide a benefit
      over that of outpatient dose-dense MegaCEOP chemotherapy.

PMID- 15951293
TI  - Long-term outcome of localized high-grade non-Hodgkin's lymphoma treated with
      high dose CHOP regimen and involved field radiotherapy: results of a GOELAMS
      study.
AB  - BACKGROUND AND OBJECTIVES: Most patients with localized high-grade non-Hodgkin's
      lymphoma (NHL) can be cured with or without adjuvant radiotherapy. However few
      data are available on the long-term outcome of these patients. Here we report the
      results of a prospective study, started in 1984, which was conducted to evaluate
      the long-term outcome of patients with localized high-grade NHL. DESIGN AND
      METHODS: In this multicenter, prospective study by the GOELAMS group, 253
      patients with localized high-grade NHL were treated with 3 cycles of vindesine,
      cyclophosphamide, adriamycin and prednisone (VCAP, a high-dose CHOP regimen)
      followed by involved field radiotherapy (40 Gy). RESULTS: After completion of
      chemotherapy, 213 patients (84%) entered complete remission (CR) and 30 (12%)
      obtained a partial remission. Treatment failed in 6 patients (2.5%) and there
      were 4 toxic deaths (1.5%). Following radiotherapy, 239 (94%) of all patients
      were in CR. With a median follow-up of 88 months, overall survival and disease
      free survival rates were 84% and 85% respectively at five years, and 78% and 82%
      respectively at ten years. The response to chemotherapy was decisive to survival.
      We observed 43 relapses (17%) at a median time of 20 months after CR, and 9
      patients relapsed after five years. Eleven patients (3%) developed another
      malignancy in the follow-up period. INTERPRETATION AND CONCLUSIONS: High-dose
      CHOP followed by locoregional radiotherapy is a feasible treatment for localized
      high-grade NHL. It has very few complications, a good CR rate and the OS is 78%
      at 10 years.

PMID- 15951294
TI  - Role of the hypoxic bone marrow microenvironment in 5T2MM murine myeloma tumor
      progression.
AB  - BACKGROUND AND OBJECTIVES: Unlike most other tumors, multiple myeloma (MM) cells
      have to survive and to grow in a bone marrow (BM) microenvironment which is
      already hypoxic by nature. BM hypoxia is crucial for normal hematopoiesis.
      However, how BM hypoxia and MM affect each other is unknown. We addressed this
      topic in the 5T2MM mouse model. DESIGN AND METHODS: Levels of hypoxia in the BM
      of control and tumor-bearing mice were analyzed by flow cytometric analysis of
      pimonidazole hypoxyprobe binding and hypoxia-inducible factor 1alpha (HIF-1alpha)
      expression. Micro-vessel density was measured by CD31 staining of BM sections for
      immunohistochemistry. Apoptosis sensitivity of CD45 5T2MM subsets in hypoxic
      conditions were analyzed by detection of active caspase-3. RESULTS: Analysis of
      control and 5T2MM diseased mice injected with pimonidazole hypoxyprobe indicated
      that both normal BM and myeloma-infiltrated BM are hypoxic. However, the hypoxia
      in the myelomatous BM was significantly decreased. Analysis of HIF-1alpha
      expression, a surrogate marker of hypoxia, also demonstrated significantly lower
      levels of hypoxia in myeloma-infiltrated BM. HIF-1alpha expression was inversely
      correlated with the micro-vessel density. In vitro culture of 5T2MM cells under
      hypoxic conditions indicated induction of apoptosis in the CD45- MM-fraction, but
      not in the CD45+ 5T2MM-cells. INTERPRETATION AND CONCLUSIONS: These data suggest
      that native BM hypoxia is advantageous for the tumor-initiating CD45+ 5T2MM
      cells. Together with the decreased hypoxia in myeloma-infiltrated BM it also
      indicates that myeloma-associated angiogenesis is functional and permissive for
      the expansion of CD45- 5T2MM-cells. All together the data raise the possibility
      of an important role of BM hypoxia in myeloma tumor progression.

PMID- 15951295
TI  - Patients with hereditary hemorrhagic telangiectasia have increased plasma levels
      of vascular endothelial growth factor and transforming growth factor-beta1 as
      well as high ALK1 tissue expression.
AB  - BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT), an
      inherited vascular dysplasia, is caused by mutations in endoglin or activin
      receptor-like kinase (ALK)-1. Haploinsufficiency for these genes is thought to
      result in an imbalanced angiogenic activity. The aim of this study was to
      evaluate the plasma levels and the expression profiles of angiogenic and
      angiogenesis-related factors in the context of HHT. DESIGN AND METHODS: Vascular
      endothelial growth factor (VEGF) and transforming growth factor (TGF)-beta1
      plasma concentrations were determined in 31 HHT patients and 40 healthy controls
      by ELISA. VEGF and TGF-beta1 plasma concentrations were correlated with the
      patients' clinicopathological features. Tissue expression of angiogenic and
      angiogenesis related proteins was determined by immunostaining on nasal cryostat
      sections from 13 HHT patients and 5 healthy controls. RESULTS: Of the 31
      patients, 29 had statistically significantly raised plasma concentrations of VEGF
      and TGF-beta1 but there was no correlation with specific clinicopathological
      features. Increased VEGF, TGF-beta1 and ALK1 immunostaining was seen in all 13
      investigated patients. beta-smooth muscle actinin immunostaining was increased in
      12 patients. Increased endoglin immunostaining was seen in only 9 patients.
      INTERPRETATION AND CONCLUSIONS: This study provides evidence of the role of VEGF
      and TGF-beta1 in the pathogenesis of HHT. Plasma concentrations of these two
      factors may serve as further diagnostic criteria for HHT. For the first time, we
      report increased TGF-beta1 plasma concentrations and increased TGF-beta1 and ALK1
      tissue expression in HHT, which appear not to be specifically associated with
      either endoglin or ALK1 mutations. The data suggest that HHT is an angiogenic
      disorder characterized by an over-expression of VEGF, TGF-beta1 and ALK1.

PMID- 15951296
TI  - Assessment of a therapeutic strategy for adults with severe autoimmune
      thrombocytopenic purpura based on a bleeding score rather than platelet count.
AB  - BACKGROUND AND OBJECTIVES: The optimal treatment for patients with autoimmune
      thrombocytopenic purpura (AITP) and a platelet count < or =20x10(9)/L is
      intravenous immunoglobulin (IVIg) but this treatment is expensive and steroids
      are a good alternative in less severe cases. Since the occurrence of life
      threatening hemorrhage in adult AITP is a rare event, the aim of our study was to
      validate a therapeutic strategy based on a bleeding score for the short-term
      management of adults with AITP and a platelet count < or =20x10(9)/L. DESIGN AND
      METHODS: We developed a method to quantify hemorrhage in adults with AITP.
      Bleeding severity was graded on a numerical scale based on physical examination.
      When the bleeding score was < or =8, the patients were treated with steroids
      alone. For scores >8, patients received IVIg (1 to 2 g/kg) in combination with
      oral steroids. A good response was defined as the lowering of the initial
      bleeding score within 2 days after treatment initiation regardless of the
      platelet count. RESULTS: We applied this strategy for the management of 60
      consecutive adults (mean age 48+/-23 years) with AITP and a platelet count < or
      =20x10(9)/L/L (mean platelet count 6+/-5x10(9)/L/L). Based on this strategy, IVIg
      was required in only 50% of the patients and no life-threatening bleeding
      occurred in patients treated with steroids alone. INTERPRETATION AND CONCLUSIONS:
      A therapeutic strategy based on a bleeding score rather than the platelet count
      appears to be relevant and safe and is a good IVIg-sparing strategy.

PMID- 15951297
TI  - Prevention of platelet-polymorphonuclear leukocyte interactions: new clues to the
      antithrombotic properties of parnaparin, a low molecular weight heparin.
AB  - BACKGROUND AND OBJECTIVES: Heparin might possess anti-thrombotic properties other
      than anticoagulation. The aim of the present study was to test the effects of a
      low-molecular weight heparin, parnaparin, on adhesive molecule-mediated platelet
      polymorphonuclear (PMN) leukocyte interactions and on PMN function. DESIGN AND
      METHODS: Platelets and PMN were isolated from citrated blood from healthy
      subjects. Pre-activated platelets incubated with PMN under dynamic conditions
      formed mixed cell aggregates. In previous experiments PMN were stimulated in
      vitro by purified P-selectin or formyl-methionyl-leucyl-phenylalanine (fMLP).
      Dual color flow cytometry was used to detect the formation of platelet-PMN mixed
      cell aggregates, and PMN activation was tested for by measuring L-selectin
      shedding, tissue factor expression and PMN degranulation. The effect of
      parnaparin was compared to that of unfractionated heparin. RESULTS: Parnaparin,
      at a concentration of 0.3-0.8 IUaXa/mL, inhibited the formation of mixed cell
      aggregates (48.8+/-9.7% of total PMN population) by up to 60% in a concentration
      dependent manner, while heparin inhibited aggregation up to 40%. Parnaparin, (0.3
      0.8 IUaXa/mL), prevented L-selectin shedding from PMN, which was induced by
      purified P-selectin (5 mg/mL) or fMLP (0.5 mmol/L) by 65% and 67%, respectively.
      Inhibition was independent of incubation time (5-20 min). Parnaparin (0.8
      IUaXa/mL) also inhibited tissue factor expression on PMN (% of positive cells),
      which was induced by P-selectin or fMLP (185+/-10 and 241+/-80% of basal value,
      respectively). Parnaparin protected PMN from degranulation after challenge with
      either stimulus (>95% inhibition). All the effects of parnaparin were observed
      with heparin at similar concentrations, although to a lesser extent and were
      often not significantly different from events in controls. INTERPRETATION AND
      CONCLUSIONS: In conclusion, the process of depolymerization of heparin to obtain
      low molecular weight parnaparin resulted in an increased, anticoagulant
      independent effect on PMN function. Thus, the overall anti-thrombotic properties
      of parnaparin may be partly due to a leukocyte-mediated anti-inflammatory effect.

PMID- 15951298
TI  - Standard practice and controversial issues in front-line therapy of acute
      promyelocytic leukemia.
AB  - In addition to choosing a state-of-the-art regimen including all-transretinoic
      and anthracycline chemotherapy, modern management of acute promyelocytic leukemia
      (APL) implies the adoption of appropriate supportive measures, rapid
      establishment of an accurate genetic diagnosis, correct assessment of response to
      therapy and evaluation of the risk of disease recurrence by molecular monitoring.
      However, the general consensus about this overall strategy for APL treatment
      still leaves room for a number of controversial issues. In the present article,
      we review the current standard practice and controversial issues in the treatment
      of patients with newly diagnosed APL, including the management of special
      situations such as elderly patients, children and pregnant women.

PMID- 15951299
TI  - Hepatitis C and health-related quality of life among patients with hemophilia.
AB  - Hepatitis C has a negative effect on health-related quality of life (HRQoL). It
      is not clear whether hepatitis C affects HRQoL of patients with hemophilia. The
      objective of this study was to assess the effect of hepatitis C virus (HCV)
      infection on HRQoL in patients with hemophilia. A cross-sectional study was
      performed among all registered hemophilia patients in the Netherlands. HRQoL was
      determined by using the self-administered SF-36 questionnaire. Patients were
      eligible for the study if they completed the SF-36, had been treated with
      clotting factor products before 1992, and had reported their hepatitis C status.
      Data on the severity of hemophilia were obtained from the hemophilia treatment
      centers. The validity of the self-reported data on hepatitis C status was
      verified in a random sample of 92 (15%) patients; 92% reported their hepatitis C
      status correctly. Fifty-five percent (333/602) of the study population had a
      current HCV infection. All eight domains of the SF-36 were lower in patients with
      a current HCV infection than they were in patients who had never been infected
      with HCV. After adjustment for age, severity of hemophilia, human
      immunodeficiency virus (HIV) status, employment status, and joint limitations,
      hepatitis C infection was associated with a decrease of HRQoL on the domains of
      general health (difference 6.9 [95% confidence interval (C.I.) 2.7 to 11.2]) and
      vitality (3.8 [95% C.I. 0.1 to 7.7]). Hemophilia patients infected with HCV
      scored lower on the HRQoL domains of general health and vitality than hemophilia
      patients who had never been infected with HCV.

PMID- 15951300
TI  - Thrombotic and bleeding complications in four subpopulations of patients with
      essential thrombocythemia defined by c-Mpl protein expression and PRV-1 mRNA
      levels.
AB  - C-Mpl and PRV-1 expression was measured in a cohort of 48 patients with essential
      thrombocythemia (ET). A retrospective analysis was conducted to asses whether the
      presence of one or both markers correlates with a higher risk of developing
      thromboembolic complications. In this cohort, PRV-1 overexpression was associated
      with a significantly increased risk of thrombosis, whereas decreased c-Mpl
      expression was not. The results of this retrospective analysis must now be
      corroborated in a large, prospective trial of newly diagnosed patients.

PMID- 15951301
TI  - Mutations of PTPN11 are rare in adult myeloid malignancies.
AB  - The PTPN11 gene encodes the phospho-tyrosyine phosphatase protein SHP-2.
      Constitutional mutations of this gene are involved in Noonan's syndrome, a
      developmental disorder in which children have a predisposition to develop a
      myeloid disorder called juvenile myelomonocytic leukemia. Recently, studies have
      shown that somatic mutations of PTPN11 can be found in children with myeloid
      malignancies. We evaluated the incidence of acquired mutation of PTPN11 in 76
      adults with acute or chronic myeloid malignancies and summarized our results
      together with others published recently.

PMID- 15951302
TI  - The relative levels of cyclin D1a and D1b alternative transcripts in mantle cell
      lymphoma may depend more on sample origin than on CCND1 polymorphism.
AB  - The relative levels of cyclin D1 (CCND1) (a) and (b) transcripts were determined
      by real-time reverse transcription polymerase chain reaction (RT-PCR) and found
      to vary according to the tissue origin in both control and tumor samples. A five
      fold overexpression of both isoforms was observed in 28/38 cases of mantle cell
      lymphoma (MCL) and of only one isoform in 10/38 MCL. No correlation was observed
      between expression of cyclin D1 isoforms and CCND1 genotype at position 870.

PMID- 15951303
TI  - Rituximab monotherapy for splenic marginal zone lymphoma.
AB  - In this retrospective study, rituximab was found to be effective therapy in 10 of
      11 patients with splenic marginal zone lymphoma, inducing prompt reduction in
      splenomegaly, improvement in blood counts in 9 patients and clearance of a
      pleural effusion in 1 patient. Median response duration was 21 months (range 4 to
      37 months). Two patients who relapsed at 21 and 23 months responded to
      retreatment. Rituximab should be considered in patients who are poor candidates
      for splenectomy.

PMID- 15951304
TI  - Correlation between fatigue and hemoglobin level in multiple myeloma patients:
      results of a cross-sectional study.
AB  - This cross-sectional study showed a positive correlation between fatigue-related
      quality of life, evaluated with the FACT-An questionnaire, and hemoglobin level
      in 1071 patients with multiple myeloma. Multiple regression analysis adjusting
      for several covariates was used. Improved FACT-An scores in women and men were
      associated with hemoglobin increase up to sex-specific normal values.

PMID- 15951305
TI  - Retrospective analysis of 472 Chinese children with chronic idiopathic
      thrombocytopenic purpura: a single center experience.
AB  - We retrospectively analyzed the clinical characteristics and management of 472
      Chinese children (age 1~14 years) with chronic idiopathic thrombocytopenic
      purpura (ITP). The distribution of cases by age showed a maximum at 4 years and
      more patients below 7 years old than between 7 and 14 years old had ITP (337,
      71.4% vs. 135, 28.6%). Variable bleeding signs occurred in this series of
      patients. Steroids therapy was effective for Chinese children with chronic ITP
      whether as first- or second-line therapy. Traditional Chinese medicine was less
      effective than steroids.

PMID- 15951307
TI  - Efficient sorting of genomic permutations by translocation, inversion and block
      interchange.
AB  - MOTIVATION: Finding genomic distance based on gene order is a classic problem in
      genome rearrangements. Efficient exact algorithms for genomic distances based on
      inversions and/or translocations have been found but are complicated by special
      cases, rare in simulations and empirical data. We seek a universal operation
      underlying a more inclusive set of evolutionary operations and yielding a
      tractable genomic distance with simple mathematical form. RESULTS: We study a
      universal double-cut-and-join operation that accounts for inversions,
      translocations, fissions and fusions, but also produces circular intermediates
      which can be reabsorbed. The genomic distance, computable in linear time, is
      given by the number of breakpoints minus the number of cycles (b-c) in the
      comparison graph of the two genomes; the number of hurdles does not enter into
      it. Without changing the formula, we can replace generation and re-absorption of
      a circular intermediate by a generalized transposition, equivalent to a block
      interchange, with weight two. Our simple algorithm converts one multi-linear
      chromosome genome to another in the minimum distance.

PMID- 15951306
TI  - Bortezomib treatment followed by a second non-myeloablative allogeneic stem cell
      transplant in two previously autografted patients with multiple myeloma relapse.
AB  - We report two cases of multiple myeloma relapse and progression following a
      combination of autologous stem cell transplantation and non-myeloablative
      allogeneic stem cell transplantation. After failure of donor lymphocyte infusions
      and thalidomide salvage therapy, the patients were treated successfully with
      bortezomib and eventually underwent a second non-myeloablative allogeneic stem
      cell transplantation.

PMID- 15951308
TI  - RAS mutation in acute myeloid leukemia is associated with distinct cytogenetic
      subgroups but does not influence outcome in patients younger than 60 years.
AB  - The pathogenesis of acute myeloid leukemia (AML) involves the cooperation of
      mutations promoting proliferation/survival and those impairing differentiation.
      The RAS pathway has been implicated as a key component of the proliferative drive
      in AML. We have screened AML patients, predominantly younger than 60 years and
      treated within 2 clinical trials, for NRAS (n = 1106), KRAS (n = 739), and HRAS
      (n = 200) hot-spot mutations using denaturing high-performance liquid
      chromatography or restriction fragment length polymorphism (RFLP) analysis. NRAS
      mutations were confirmed in 11% of patients (126/1106) and KRAS mutations in 5%
      (39/739). No HRAS mutations were detected in 200 randomly selected samples.
      Codons most frequently mutated were N12 (43%), N13 (21%), and K12 (21%). KRAS
      mutations were relatively overrepresented in French-American-British (FAB) type
      M4 (P < .001). NRAS mutation was over-represented in the t(3;5)(q21 approximately
      25;q31 approximately q35) subgroup (P < .001) and underrepresented in
      t(15;17)(q22;q21) (P < .001). KRAS mutation was overrepresented in
      inv(16)(p13q22) (P = .004). Twenty-three percent of KRAS mutations were within
      the inv(16) subgroup. RAS mutation and FLT3 ITD were rarely coexistent (14/768; P
      < .001). Median percentage of RAS mutant allele assayed by quantitative RFLP
      analysis was 28% (N12), 19% (N13), 25% (N61), and 21% (K12). RAS mutation did not
      influence clinical outcome (overall/disease-free survival, complete remission,
      relapse rate) either for the entire cohort or within cytogenetic risk groups.

PMID- 15951309
TI  - Lung resection in patients with preoperative FEV1 < 35% predicted.
AB  - OBJECTIVES: To determine the morbidity, mortality, and feasibility of lung
      resection in patients with tumors and preoperative FEV1 < 35% predicted. DESIGN:
      Retrospective review. SETTING: A 734-bed, tertiary care, academic hospital with a
      dedicated general thoracic surgery unit performing > 2,000 operations per year.
      PATIENTS: One hundred consecutive patients with discrete lung tumors and with
      preoperative FEV1 < 35% predicted undergoing lung resection between September
      1997 and May 2003. Only operations with curative intent were included. Average
      preoperative predicted FEV1 was 26%. Sixteen percent of the patients were oxygen
      dependent prior to the operation. RESULTS: Open and thoracoscopic wedge
      resections, segmentectomies, lobectomies, and combined lung resections with lung
      volume reduction were performed. Sixty-six of the lesions were malignant, and 57
      were primary lung cancers. Only one patient left the operating room with positive
      margins. There was one in-hospital or 30-day mortality. Thirty-six percent of the
      patients had one or more complications. Twenty-two percent of the patients had
      prolonged air leaks requiring a chest tube for > 7 days. One patient left the
      hospital ventilator dependent, 3 additional patients required intubation > 48 h,
      and 11 patients were discharged with a new oxygen requirement. There were four
      pneumonias, one myocardial infarction, and two reoperations for bleeding. Male
      gender (p = 0.003), preoperative oxygen dependence (p = 0.03), and pack-year
      history (p = 0.006) were associated with a higher overall incidence of
      complications, while age, incision, diabetes, coronary artery disease, duration
      of smoking cessation, amount of lung resected, size of lesion, and preoperative
      percentage of predicted FEV1 did not correlate with the overall incidence of
      complications. CONCLUSIONS: In a large academic center, minimally invasive
      surgical techniques, intensive pulmonary care, and advanced anesthetic techniques
      allow for curative lung tumor resections in patients with very low preoperative
      FEV1 with a very low mortality and very low incidence of ventilator dependence.
      Other serious complications such as pneumonia, myocardial infarction, and
      bleeding are uncommon. An extended hospital stay and a high incidence of
      prolonged air leak should be expected, especially in patients with preoperative
      FEV1 < or = 20% predicted.

PMID- 15951310
TI  - Treatment of head louse infestation with 4% dimeticone lotion: randomised
      controlled equivalence trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of 4% dimeticone lotion for
      treatment of head louse infestation. DESIGN: Randomised controlled equivalence
      trial. SETTING: Community, with home visits. PARTICIPANTS: 214 young people aged
      4 to 18 years and 39 adults with active head louse infestation. INTERVENTIONS:
      Two applications seven days apart of either 4.0% dimeticone lotion, applied for
      eight hours or overnight, or 0.5% phenothrin liquid, applied for 12 hours or
      overnight. OUTCOME MEASURES: Cure of infestation (no evidence of head lice after
      second treatment) or reinfestation after cure. RESULTS: Cure or reinfestation
      after cure occurred in 89 of 127 (70%) participants treated with dimeticone and
      94 of 125 (75%) treated with phenothrin (difference -5%, 95% confidence interval 
      16% to 6%). Per protocol analysis showed that 84 of 121 (69%) participants were
      cured with dimeticone and 90 of 116 (78%) were cured with phenothrin. Irritant
      reactions occurred significantly less with dimeticone (3/127, 2%) than with
      phenothrin (11/125, 9%; difference -6%, -12% to -1%). Per protocol this was 3 of
      121 (3%) participants treated with dimeticone and 10 of 116 (9%) treated with
      phenothrin (difference -6%, -12% to -0.3%). CONCLUSION: Dimeticone lotion cures
      head louse infestation. Dimeticone seems less irritant than existing treatments
      and has a physical action on lice that should not be affected by resistance to
      neurotoxic insecticides.

PMID- 15951311
TI  - Improving the quality of child health services: participatory action by
      providers.
AB  - OBJECTIVE: To test a quality improvement approach called COPE (Client-Oriented,
      Provider-Efficient services), for use in strengthening health systems and
      supporting Integrated Management of Child Health (IMCI) efforts. DESIGN: Pre- and
      post-intervention observations of client/provider interactions, facility audits,
      staff and client surveys, and focus groups to evaluate differences between eight
      COPE intervention and eight matched non-intervention facilities after a 15-month
      intervention in 2001. SETTING: Primary care clinics in Guinea and Kenya. STUDY
      PARTICIPANTS: Health care providers and child caregivers. INTERVENTIONS: Over 15
      months, the intervention supported four COPE exercises at each intervention site,
      supported supervisor training in quality management, and organized minimal
      training in topics selected by site staff as areas where training was needed.
      MAIN OUTCOME MEASURES: Differences in staff's and child caregiver's knowledge,
      attitudes, and practices; differences in the quality of services provided.
      RESULTS: On almost every quality indicator (over 65 indicators), whether reported
      by staff, observed by evaluators, or reported by clients, the intervention sites
      performed statistically significantly better than control sites. INTERVENTION:
      sites were cleaner and more pleasant, with more respect and information for
      clients, and more privacy. Staff had better personal communication skills, better
      diagnostic skills, and prescribing practices and gave better home care
      instructions to carers. Clients in intervention sites were more informed and more
      satisfied, and their children had better immunization coverage than those in
      control sites. CONCLUSION: COPE is a simple process, yet our study confirms that
      it can have a very dramatic effect on the quality of services. This study
      demonstrated how all areas of quality can be addressed by empowering health care
      providers to take action by using COPE. We suggest that COPE can complement
      Integrated Management of Childhood Illness (IMCI) training and can help to
      achieve better health for children.

PMID- 15951312
TI  - Are family members suitable proxies for transitional care unit residents when
      collecting satisfaction information?
AB  - OBJECTIVE: To examine the agreement and association of elders' responses with
      family member proxy responses using the same, previously validated satisfaction
      instrument on both groups of respondents. METHODS: Satisfaction data came from
      transitional care unit residents and family members (N = 462 paired responses)
      from one facility and were collected between 1999 and 2000. The satisfaction
      questionnaire consisted of 17 items evaluating the art of care, technical
      quality, efficacy, amenities of the care environment, and global satisfaction.
      Bias indexes and intraclass correlation coefficients were used to examine the
      satisfaction scores. RESULTS: In general, proxy satisfaction ratings were higher
      than ratings of residents. The results also show that proxy ratings varied less
      from resident ratings for the amenity items, which were considered the most
      concrete items. Proxy ratings were much higher for the art of care and efficacy
      domain items, which were considered the least concrete items. CONCLUSION: The
      results of this investigation show that proxy ratings do not necessarily
      substitute for resident ratings.

PMID- 15951313
TI  - Cross-reactivity of amino acids and other compounds in the biuret reaction:
      interference with urinary peptide measurements.
AB  - BACKGROUND: Biuret assays for total protein measurement are considered to react
      with all peptides longer than 2 residues. Some studies using biuret assays of
      urine suggest that small peptides generally are more abundant than proteins in
      urine, but it is not clear whether this is a problem of assay specificity.
      METHODS: We analyzed the specificity and kinetics of a biuret reaction for
      solutions of amino acids, organic compounds, peptides, proteins, and
      ultrafiltered urine specimens and compared the results with standard clinical
      assays for protein measurement. RESULTS: The biuret assay cross-reacted with
      several amino acids, dipeptides, and other organic compounds able to form 5- or 6
      member ring chelation complexes with copper. Reactions with amino acids and
      dipeptides had higher absorbance maxima (blue color) than with larger peptides
      and proteins (purple). Compounds forming potential 4-, 7-, 8-, or 9-member ring
      complexes with copper had low reactivity. Amino acid amides, dipeptides, and
      longer peptides had substantial reactivity, except those containing proline.
      Proteins and polypeptides had similar biuret reactivities per peptide bond, but
      reaction kinetics were slower for proteins than peptides. Urine specimens
      ultrafiltered through 3-kDa-cutoff membranes had substantial biuret reactivity,
      but absorbance maxima were consistent with cross-reactive amino acids rather than
      peptides. CONCLUSIONS: Many compounds, including amino acids, amino acid
      derivatives, and dipeptides, cross-react in biuret assays. Our studies improve
      understanding of the specificity of endpoint and kinetic biuret assays widely
      used in clinical laboratories. Amino acids, urea, and creatinine contribute to
      overestimation of urinary peptide content by biuret assays.

PMID- 15951314
TI  - Association between hydrogen peroxide-dependent byproducts of ascorbic acid and
      increased hepatic acetyl-CoA carboxylase activity.
AB  - BACKGROUND: Parenteral multivitamin preparation (MVP) induces fatty liver in
      neonatal guinea pig pups; this is prevented by photoprotection. Photo-excited
      riboflavin present in MVP generates H(2)O(2) and molecules with masses of 136 and
      208. We hypothesized that H(2)O(2) initiates the peroxidation of ascorbic acid
      (AA), producing biologically active byproducts affecting hepatic lipid
      metabolism. METHODS: Mass spectrometry (MS) documented the participation of
      H(2)O(2) and photo-excited riboflavin (Ribo) in the formation of AA byproducts.
      Sixteen 3-day-old guinea pig pups received an intravenous solution (50 g/L
      dextrose + 4.5 g/L NaCl + 1 kIU/L heparin) at 240 mL x kg(-1) x day(-1), enriched
      with control or test mixtures, for 4 days. The control mixture was photo
      protected AA + Ribo (without byproducts or H(2)O(2)), and the test mixture was AA
      + Ribo treated to generate AA byproducts without H(2)O(2). Hepatic acetyl-CoA
      carboxylase (ACC) activity was determined after 4 days. Fourth-day urine samples
      were analyzed by MS. Data were treated by ANOVA (alpha = 0.05). RESULTS: H(2)O(2)
      did not influence the classic degradation of AA, as the generation of 2,3
      diketogulonic acid was not affected. In contrast, the formation of molecules with
      masses of 136 and 208 was H(2)O(2) and time dependent. ACC activity was higher (P
      <0.01) in animals receiving high concentration of these molecules; its hepatic
      activation correlated (P <0.01) with the urinary concentration of molecule-208.
      CONCLUSIONS: H(2)O(2) at concentrations found in the clinical setting of total
      parenteral nutrition induce the transformation of dehydroascorbic acid into
      compounds that have the potential to affect lipid metabolism. These molecules
      have peroxide and aldehyde functions.

PMID- 15951315
TI  - beta-Trace protein is an alternative marker for glomerular filtration rate in
      renal transplantation patients.

PMID- 15951316
TI  - Prognostic value of serum concentration of heart-type fatty acid-binding protein
      relative to cardiac troponin T on admission in the early hours of acute coronary
      syndrome.
AB  - BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is proposed as an
      early biomarker for acute myocardial infarction (AMI), but its prognostic value
      is unclear in acute coronary syndrome (ACS). We evaluated the prognostic value of
      the H-FABP concentration relative to cardiac troponin T (cTnT) in the early hours
      of ACS. METHODS: Serum concentrations of H-FABP and cTnT were measured on
      admission in 328 consecutive patients hospitalized for ACS within 6 h after the
      onset of chest pain [AMI, 241 (73.5%) patients; ST-segment elevation myocardial
      infarction, 154 (47.0%) patients; and emergent coronary angiography within 24 h
      after admission, 287 (87.5%) patients]. Cardiac events, which were defined as
      cardiac death or subsequent nonfatal AMI, were monitored for 6 months after
      admission. RESULTS: During the 6-month follow-up period, there were 25 cardiac
      events, including 15 cardiac deaths and 10 subsequent nonfatal AMIs. Stepwise
      multivariate analyses including clinical, electrocardiographic, and biochemical
      variables revealed that increased H-FABP (above the median of 9.8 microg/L), but
      not increased cTnT (above the median of 0.02 microg/L), was independently
      associated with cardiac events in all patients [relative risk (RR) = 8.96; P =
      0.0004], the subgroup of patients with ST-segment elevation myocardial infarction
      (RR = 11.3; P = 0.02), and the subgroup of patients with unstable angina and non
      ST-segment elevation myocardial infarction (RR = 8.31; P = 0.007). The area under
      the ROC curve was higher for H-FABP than for cTnT (0.711 vs 0.578; P = 0.08),
      suggesting that H-FABP concentrations have a greater predictive capacity for
      cardiac events than cTnT. CONCLUSION: Serum H-FABP is a potential independent
      predictor of cardiac events within 6 months of patient admission and may provide
      prognostic information superior to cTnT in the early hours of ACS.

PMID- 15951317
TI  - The uncoupling protein 2 Ala55Val polymorphism is associated with diabetes
      mellitus: the CARDIA study.
AB  - BACKGROUND: Uncoupling proteins (UCPs) reduce ATP generation with concomitant
      increased release of heat. The activities of UCPs have been related to obesity
      and energy metabolism. METHODS: We investigated the association of the commonly
      observed UCP2 Ala55Val (V) polymorphism with diabetes mellitus and impaired
      fasting glucose (IFG) among 3684 participants in the Coronary Artery Risk
      Development in Young Adults (CARDIA) study. RESULTS: The V frequency was
      approximately 45% in blacks and 42% in whites. Those with the Val/Val (VV)
      genotype had a higher incidence of diabetes than those having the Ala/Ala (AA)
      genotype (5.8% vs 3.3%; P = 0.02). Similarly, the incidences of diabetes in
      participants without abdominal obesity were 2.8% and 1.0% (P = 0.03) in the VV
      and AA groups, and 12.4% and 8.3% (P = 0.15) in participants with abdominal
      obesity. The incidence of IFG was higher in VV vs AA only in those without
      abdominal obesity (12.9% vs 9.2%). These trends persisted in minimally and fully
      adjusted models, and in strata of blacks and whites and men and women. The
      homeostasis model assessment for insulin resistance was highest in VV in the
      combined group of those with IFG or untreated diabetes, but not in those with
      normal fasting glucose. CONCLUSION: The VV genotype of the UCP2 polymorphism was
      positively related to diabetes. It may involve increased insulin resistance in
      those with impaired glucose homeostasis.

PMID- 15951318
TI  - Preparation and characterization of candidate reference materials for telomerase
      assays.
AB  - BACKGROUND: Telomerase has been measured in body fluids of cancer patients, and
      clinical tests for telomerase may have utility as noninvasive, cost-effective
      methods for the early detection of cancer. However, telomerase activity measured
      by common methods such as the telomerase repeat amplification protocol (TRAP) and
      telomerase reverse transcriptase catalytic subunit (hTERT) mRNA by reverse
      transcription-PCR (RT-PCR) varies among laboratories. METHODS: We prepared a
      CHAPS buffer lysate from cultured A549 cells and stored it at -80 degrees C.
      Telomerase activity was measured by TRAP/PCR and real-time TRAP/PCR in
      conjunction with RT-PCR measurements of hTERT mRNA. Activity measured with use of
      the robot-assisted TRAP (RApidTRAP) multicapillary electrophoresis system was
      compared with single-capillary and slab-gel measurements in the range 10 to 10
      000 cell equivalents. RESULTS: Preparations made after flash freezing and
      sonication of cells were approximately 3-fold more active. Although the slab-gel
      and capillary instruments detected telomerase activity, the multicapillary
      instrument was better suited for high-throughput studies. Measurements of
      telomerase by TRAP/real-time PCR and hTERT mRNA/RT-PCR yielded reproducible
      titrations in the range 10 to 10 000 cell equivalents (CVs, 1%-8% and 1%-3%,
      respectively). CONCLUSIONS: We have prepared and characterized a candidate
      reference material that appears to be suitable for use in a wide range of assays
      of telomerase activity and expression.

PMID- 15951319
TI  - Analytical and preanalytical biases in serum proteomic pattern analysis for
      breast cancer diagnosis.

PMID- 15951320
TI  - Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus.
AB  - BACKGROUND: Tacrolimus is metabolized predominantly to 13-O-demethyltacrolimus in
      the liver and intestine by cytochrome P450 3A (CYP3A). Patients with high
      concentrations of CYP3A5, a CYP3A isoenzyme polymorphically produced in these
      organs, require higher doses of tacrolimus, but the exact mechanism of this
      association is unknown. METHODS: cDNA-expressed CYP3A enzymes and a bank of human
      liver microsomes with known CYP3A4 and CYP3A5 content were used to investigate
      the contribution of CYP3A5 to the metabolism of tacrolimus to 13-O
      demethyltacrolimus as quantified by liquid chromatography-tandem mass
      spectrometry. RESULTS: Demethylation of tacrolimus to 13-O-demethyltacrolimus was
      the predominant clearance reaction. Calculated K(m) and V(max) values for CYP3A4,
      CYP3A5, and CYP3A7 cDNA-expressed microsomes were 1.5 micromol/L and 0.72 pmol x
      (pmol P450)(-1) x min(-1), 1.4 micromol/L and 1.1 pmol x (pmol P450)(-1) x min(
      1), and 6 micromol/L and 0.084 pmol x (pmol P450)(-1) x min(-1), respectively.
      Recombinant CYP3A5 metabolized tacrolimus with a catalytic efficiency
      (V(max)/K(m)) that was 64% higher than that of CYP3A4. The contribution of CYP3A5
      to 13-O-demethylation of tacrolimus in human liver microsomes varied from 1.5% to
      40% (median, 18.8%). There was an inverse association between the contribution of
      CYP3A5 to 13-O-demethylation and the amount of 3A4 protein (r = 0.90; P <0.0001).
      Mean 13-O-demethylation clearances in CYP3A5 high and low expressers, estimated
      by the parallel-tube liver model, were 8.6 and 3.57 mL x min(-1) x (kg of body
      weight)(-1), respectively (P = 0.0088). CONCLUSIONS: CYP3A5 affects metabolism of
      tacrolimus, thus explaining the association between CYP3A5 genotype and
      tacrolimus dosage. The importance of CYP3A5 status for tacrolimus clearance is
      also dependent on the concomitant CYP3A4 activity.

PMID- 15951321
TI  - Six novel mutations in the proopiomelanocortin and melanocortin receptor 4 genes
      in severely obese adults living in southern Italy.
AB  - BACKGROUND: The genetic characterization of obese individuals could clarify the
      molecular mechanisms underlying body weight regulation and lead to targeted
      therapy. Here we report variants of the proopiomelanocortin (POMC) and
      melanocortin receptor 4 (MC4R) genes detected in severely obese adults living in
      southern Italy. METHODS: A total of 196 unrelated nondiabetic severely obese
      individuals [111 females and 85 males; mean (SD) age, 32.2 (11.5) years; mean
      body mass index, 48.8 (8.1) kg/m(2)] and 100 normal-weight healthy volunteers (34
      males and 66 females) entered the study. POMC and MC4R were genotyped by
      sequencing analysis. Leptin, insulin, glucose, and the lipid profile were
      measured in fasting serum samples. We used the protein truncation test to verify
      the stop-codon mutation. Anthropometric measurements, sitting blood pressure, and
      heart rate were also recorded. RESULTS: Of the obese participants, 1.5% had
      mutations in POMC exon 3 (new mutations, P231L and E244X; known, R236G) and 2.5%
      had MC4R mutations (new mutations, W174C, Q43X, S19fsX51, and I317V; known,
      A175T). These mutations were not present in the controls. Gene polymorphisms were
      identified in similar percentages of severely obese and nonobese individuals,
      i.e., respectively, 52.5% and 51% (POMC) and 1% and 2% (MC4R). CONCLUSIONS: We
      detected 2 new POMC mutations and 4 new MC4R mutations in a large number of
      severely obese adults living in southern Italy. These mutations, not present in
      normal-weight individuals, are further evidence that defects in the melanocortin
      pathway are related to severe obesity.

PMID- 15951322
TI  - Development of a PCR-based assay for detection, quantification, and genotyping of
      human adenoviruses.
AB  - BACKGROUND: Adenoviruses (AdVs) can cause serious disease in immunosuppressed
      patients, particularly those undergoing allogeneic stem cell transplantation. A
      method for virus quantification in clinical specimens is essential for monitoring
      patient adenoviral loads and evaluating new therapeutic approaches. METHODS: We
      developed a PCR-based assay that combines detection and genotyping of human AdVs,
      targeting a highly conserved region of the adenoviral genome coding for the DNA
      polymerase (AdV DPol PCR). We tested the diagnostic applicability of this PCR
      based assay by analyzing 159 clinical specimens from children with respiratory
      disease and comparing the results with those obtained by nested PCR analysis.
      RESULTS: The PCR assay detected all currently known AdV serotypes, with a
      detection limit of approximately 10 genome equivalents per reaction for 49 of 51
      serotypes. No cross-reactivity to human DNA or other DNA viruses was observed. In
      addition, genotyping of PCR-positive samples was achieved within minutes by
      fluorescence curve melting analysis in a LightCycler instrument using 6 pairs of
      hybridization probes, each specific for a single AdV species. Results for
      clinical specimens were in good concordance with those obtained by nested PCR.
      CONCLUSION: The presented assay is a suitable tool for the detection and
      genotyping of human AdVs in clinical samples.

PMID- 15951323
TI  - Assessment of the cough reflex after propofol anaesthesia for colonoscopy.
AB  - BACKGROUND: Dysfunction of the cough reflex as a result of the lingering effects
      of anaesthetics may lead to aspiration pneumonia or retained secretions after
      general anaesthesia. It is unknown whether low concentrations of propofol alter
      the cough reflex in the early period after anaesthesia. The objective of this
      study was to investigate the effect of low concentrations of propofol on the
      cough reflex sensitivity as assessed by the cough reflex threshold to an inhaled
      irritant. METHODS: Fifteen, ASA I-II, non-smoking patients undergoing elective
      colonoscopy were studied. Anaesthesia was induced and maintained with a blood
      target-controlled propofol infusion. Cough reflex threshold was measured with
      citric acid. Increasing concentrations of nebulized citric acid (2.5, 5, 10, 20,
      40, 80, 160, 320, and 640 mg ml(-1)) were delivered during inspiration until a
      cough was evoked. The citric acid concentration eliciting one cough (C1) was
      defined as the cough reflex threshold. C1 was log transformed for statistical
      analysis (Log C1). Log C1 was measured before anaesthesia and during the recovery
      period with estimated decreasing propofol concentrations of 1.2, 0.9, 0.6, and
      0.3 microg ml(-1). RESULTS: Log C1 (median; interquartile range) measured with
      propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 microg ml(-1) were 1.9
      (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml(-1) (NS),
      respectively. However, light sedation was observed with propofol concentrations
      of 1.2 and 0.9 microg ml(-1). CONCLUSION: This study indicates that residual
      sedation after propofol anaesthesia for colonoscopy does not adversely affect the
      cough reflex.

PMID- 15951324
TI  - Postoperative visual loss following prone spinal surgery.
AB  - Postoperative visual loss is a rare but disastrous complication that has an
      estimated incidence of 0.01-1% after non-ocular surgery. We report a patient who
      underwent a prolonged spinal operation in the prone position and complained of
      blindness in one eye postoperatively. We consider the potential aetiological
      factors contributing to this unilateral postoperative visual loss and suggest
      strategies to reduce the incidence of this complication in spinal surgery.

PMID- 15951325
TI  - Effect of clonidine pre-medication on propofol requirements during lower
      extremity vascular surgery: a randomized controlled trial.
AB  - BACKGROUND: Pre-medication with clonidine reduces the requirement for volatile
      agents during general anaesthesia. This may also be true for anaesthesia with
      propofol, but the amount of dose reduction has not been measured. Because
      clonidine also affects cardiac output and thus regional blood flow it could alter
      the pharmacokinetics of propofol. This randomized, double-blind placebo
      controlled trial aimed to study the effect of clonidine pre-medication on dose
      requirement for propofol during lower extremity vascular surgery using the
      bispectral index (BIS) as a measure of anaesthetic depth. METHODS: After oral pre
      medication with either clonidine 3 microg kg(-1) or placebo, 39 subjects had
      lower limb vascular surgery using propofol infusion for anaesthesia. Anaesthetic
      depth was adjusted to a BIS of 45. Predicted plasma propofol concentrations were
      noted every 30 min from a target-controlled propofol infusion pump and arterial
      samples were taken at the same time for propofol measurements. RESULTS: Patients
      in both groups were anaesthetized to similar depths of anaesthesia as indicated
      by BIS readings (P=0.44). The groups had comparable mean (95% CI) arterial
      concentrations of propofol, 4.8 (3.5-6.1) microg ml(-1) in the patients given
      clonidine, and 4.6 (3.4-5.7) microg ml(-1) in the patients given placebo
      (P=0.81). However, the average plasma concentration predicted by the target
      controlled infusion was less in the clonidine group [3.2 (2.9-3.5)] than in the
      group given placebo [3.6 (3.3-3.9)] microg ml(-1) (P<0.05). CONCLUSIONS: Pre
      medication with clonidine reduces the requirement for propofol, which is a
      pharmacokinetic effect and not a pharmacodynamic central sedative effect.

PMID- 15951326
TI  - Tramadol disposition in the very young: an attempt to assess in vivo cytochrome P
      450 2D6 activity.
AB  - BACKGROUND: Tramadol is potentially a very useful pain relief medication in
      neonates and infants. It is primarily metabolized into O-demethyl tramadol (M1)
      by CYP2D6. Data concerning tramadol disposition and CYP2D6 activity in young
      infants are not available. METHODS: A population pharmacokinetic analysis of
      tramadol and M1 time-concentration profiles was undertaken using non-linear mixed
      effects models (NONMEM), based on newly collected data on tramadol and M1 time
      concentration profiles in neonates and young infants (n=20) and published studies
      on intravenous tramadol in children and adults. M1 formation served as a
      surrogate for CYP2D6 activity. RESULTS: Tramadol clearance was described using a
      two-compartment linear model with zero-order input and first-order elimination.
      Clearance increased from 25 weeks post-conception age (PCA) (5.52 litre h(-1) [70
      kg](-1)) to reach 84% of the mature value by 44 weeks PCA (standardized to a 70
      kg adult using allometric '1/4 power' models). The central volume of distribution
      decreased from 25 weeks PCA (256 litre [70 kg](-1)) to reach 120% of its mature
      value by 87 weeks PCA. Formation clearance to M1 contributed 43% of tramadol
      clearance, but had no relationship with PCA. There was a weak non-linear
      relationship between PCA and M1 metabolite clearance. CONCLUSIONS: Maturational
      clearance of tramadol is almost complete by 44 weeks PCA. A target concentration
      of 300 microg litre(-1) is achieved after a bolus of tramadol hydrochloride 1 mg
      kg(-1) and can be maintained by infusion of tramadol hydrochloride 0.09 mg kg(-1)
      h(-1) at 25 weeks PCA, 0.14 mg kg(-1) h(-1) at 30 weeks PCA, 0.17 mg kg(-1) h(-1)
      at 35 weeks PCA, 0.18 mg kg(-1) h(-1) at 40 weeks, 0.19 mg kg(-1) h(-1) at 50
      weeks PCA to 1 yr, 0.18 mg kg(-1) h(-1) at 3 yr and 0.12 mg kg(-1) h(-1) in
      adulthood. CYP2D6 activity was observed as early as 25 weeks PCA, but the impact
      of CYP2D6 polymorphism on the variability in pharmacokinetics, metabolism and
      pharmacodynamics of tramadol remains to be established.

PMID- 15951327
TI  - Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane
      and remifentanil.
AB  - BACKGROUND: The aim of this study was to investigate the effects of tramadol
      administered with ketorolac on the Bispectral Index (BIS) during anaesthesia with
      sevoflurane and remifentanil. METHODS: Forty-six adult patients, ASA I-III,
      scheduled for elective minor surgical procedures were studied. Patients were
      premedicated with remifentanil infusion 0.4 microg kg(-1) min(-1) and anaesthesia
      was induced 4-5 min later with propofol 1.5 mg kg(-1) and maintained with air
      oxygen (FI(O(2)) 0.4), remifentanil 0.1-0.15 microg kg(-1) min(-1) and
      sevoflurane, adjusted to keep the BIS between 40 and 50. After 20 min of stable
      anaesthesia, the subjects were allocated randomly to receive i.v. tramadol 1.5 mg
      kg(-1) and i.v. ketorolac 0.3 mg kg(-1) (tramadol group) or saline (control
      group). BIS values, mean arterial pressure, heart rate and end-tidal carbon
      dioxide were recorded every 5 min for 20 min. RESULTS: Mean BIS values after
      tramadol administration were not significantly different from those recorded in
      patients receiving saline throughout the period of observation. There were no
      patients who presented explicit recall of events under anaesthesia. No
      significant changes in mean arterial pressure, heart rate and end-tidal carbon
      dioxide were noted after tramadol injection. CONCLUSION: Tramadol, given with
      ketorolac to prevent postoperative pain, during anaesthesia maintained with
      sevoflurane and remifentanil at BIS between 40 and 50, does not modify the BIS
      value.

PMID- 15951328
TI  - Long-term intrathecal S(+)-ketamine in a patient with cancer-related neuropathic
      pain.
AB  - Neuropathic pain sometimes needs invasive pain therapy. We present the case of a
      patient with cancer-related neuropathic pain untreatable with conventional pain
      therapy after tumour-embolization. The patient was treated successfully with
      intrathecal (i.t.) administration of S(+)-ketamine, in addition to morphine.
      Plasma concentrations of S(+)-ketamine were measured regularly throughout the
      treatment. Continuous i.t. administration of S(+)-ketamine over a period of 3
      months demonstrated low plasma levels and no unwanted side-effects.

PMID- 15951329
TI  - Mechanism of nicotine-induced pulmonary fibroblast transdifferentiation.
AB  - We tested the hypothesis that in vitro nicotine exposure disrupts specific
      epithelial-mesenchymal paracrine signaling pathways and results in pulmonary
      interstitial lipofibroblast (LIF)-to-myofibroblast (MYF) transdifferentiation,
      resulting in altered pulmonary development and function. Studies were done to
      determine whether nicotine induces LIF-to-MYF transdifferentiation and to
      elucidate underlying molecular mechanism(s) involved and to determine whether
      nicotine-induced LIF-to-MYF transdifferentiation could be prevented by
      stimulating specific alveolar interstitial fibroblast lipogenic pathway. WI38
      cells, a human embryonic pulmonary fibroblast cell line, were treated with
      nicotine with or without specific agonists of alveolar fibroblast lipogenic
      pathway, PTHrP, DBcAMP, or the potent PPARgamma stimulant rosiglitazone (RGZ) for
      7 days. Expression of key lipogenic and myogenic markers was examined by RT-PCR,
      Western hybridization, and immunohistochemistry. The effect of nicotine on
      triglyceride uptake by WI38 cells and PTHrP binding to its receptor was also
      determined. Finally, the effect of transfecting WI38 cells with a PPARgamma
      expression vector on nicotine-induced LIF-to-MYF transdifferentiation was
      determined. Nicotine treatment resulted in significantly decreased expression of
      lipogenic and increased expression of myogenic markers in a dose-dependent
      manner, indicating nicotine-induced LIF-to-MYF transdifferentiation. This was
      accompanied by decreased PTHrP receptor binding to its receptor. The nicotine
      induced LIF-to-MYF transdifferentiation was completely prevented by concomitant
      treatment with PTHrP, DBcAMP, RGZ, and by transiently overexpressing PPARgamma.
      Our data suggest nicotine induces alveolar LIF-to-MYF transdifferentiation
      through a mechanism involving downregulation of lipogenic PTHrP-mediated, cAMP
      dependent PKA signaling pathway, which can be prevented using specific molecular
      targets. Potential therapeutic implications of these observations against in
      utero nicotine-induced lung injury remain to be tested.

PMID- 15951330
TI  - Regulation of urokinase receptor expression by phosphoglycerate kinase is
      independent of its catalytic activity.
AB  - Posttranscriptional regulation of urokinase-type plasminogen activator receptor
      (uPAR) mRNA involves the interaction of a uPAR mRNA coding region sequence with
      phosphoglycerate kinase (PGK), a 50-kDa uPAR mRNA binding protein. PGK catalyzes
      a reversible transfer of a phosphoryl group from 1,3-biphosphoglycerate to ADP in
      the glycolytic pathway. Our previous studies showed that overexpression of PGK in
      uPAR-overproducing H157 lung carcinoma cells results in decreased cytoplasmic
      uPAR mRNA and cell surface uPAR protein expression through destabilization of the
      mRNA. In order to determine the role of PGK enzymatic activity on uPAR mRNA
      stability we mutated PGK by changing amino acid P204H and amino acid D219A. The
      mutant proteins were expressed in Epicurian coli BL21 cells, and the purified
      proteins were analyzed for PGK activity. We found that mutation of amino acid
      P204H and D219A reduced PGK activity by 99 and 83%, respectively. By gel mobility
      shift and Northwestern assay, we found that the mutant proteins were able to bind
      to uPAR mRNA as effectively as wild-type PGK. Overexpression of mutant, inactive
      PGK in H157 cells reduced cell surface uPAR protein as well as uPAR mRNA
      expression. Run-on transcription analysis indicated that overexpression of mutant
      PGKs fails to alter the rate of synthesis of uPAR mRNA, whereas transcription
      chase experiments demonstrated that both mutants and wild-type PGK reduce the
      stability of the uPAR mRNA transcripts to a similar extent. Overexpression of
      mutant PGK also inhibited the rate of DNA synthesis and the invasion-migration
      ratio. These results demonstrate that uPAR mRNA binding activity as well as PGK
      mediated regulation of uPAR mRNA are independent of PGK enzymatic activity.

PMID- 15951331
TI  - Prevention of NF-kappaB activation in vivo by a cell-permeable NF-kappaB
      inhibitor peptide.
AB  - The NF-kappaB/Rel transcription factor family plays a central role in
      coordinating the expression of a variety of genes that regulate stress responses,
      immune cell activation, apoptosis, proliferation, differentiation, and oncogenic
      transformation. Interventions that target the NF-kappaB pathway may be
      therapeutic for a variety of pathologies, especially immune/inflammatory
      diseases. Using membrane translocating sequence (MTS) technology, we developed a
      cell-permeable dominant inhibitor of NF-kappaB activation, termed IkappaBalpha
      (DeltaN)-MTS. This molecule contains a 12-amino acid MTS motif attached to the
      COOH-terminal region of a nondegradable inhibitor protein [IkappaBalpha
      (DeltaN)]. The recombinant protein enters cells and localizes in the cytoplasm.
      Delivery of the IkappaBalpha-(DeltaN)-MTS to cell lines and primary cells
      inhibited nuclear translocation of NF-kappaB proteins induced by cell activation.
      The protein also effectively inhibited NF-kappaB activation in vivo in two
      different animal models: NF-kappaB activation in response to skin wounding in
      mice and NF-kappaB activation in lungs after endotoxin treatment in sheep.
      Inhibition of NF-kappaB by the IkappaBalpha-(DeltaN)-MTS in the endotoxin model
      attenuated physiological responses to endotoxemia. These data demonstrate that
      activation of NF-kappaB can be inhibited using a recombinant protein designed to
      penetrate into cells. This technology may provide a new approach to NF-kappaB
      pathway-targeted therapies.

PMID- 15951332
TI  - Respiratory innate immune proteins differentially modulate the neutrophil
      respiratory burst response to influenza A virus.
AB  - Oxidants and neutrophils contribute to lung injury during influenza A virus (IAV)
      infection. Surfactant protein (SP)-D plays a pivotal role in restricting IAV
      replication and inflammation in the first several days after infection. Despite
      its potent anti-inflammatory effects in vivo, preincubation of IAV with SP-D in
      vitro strongly increases neutrophil respiratory burst responses to the virus.
      Several factors are shown to modify this apparent proinflammatory effect of SP-D.
      Although multimeric forms of SP-D show dose-dependent augmentation of respiratory
      burst responses, trimeric, single-arm forms either show no effect or inhibit
      these responses. Furthermore, if neutrophils are preincubated with multimeric SP
      D before IAV is added, oxidant responses to the virus are significantly reduced.
      The ability of SP-D to increase neutrophil uptake of IAV can be dissociated from
      enhancement of oxidant responses. Finally, several other innate immune proteins
      that bind to SP-D and/or IAV (i.e., SP-A, lung glycoprotein-340 or mucin)
      significantly reduce the ability of SP-D to promote neutrophil oxidant response.
      As a result, the net effect of bronchoalveolar lavage fluids is to increase
      neutrophil uptake of IAV while reducing the respiratory burst response to virus.

PMID- 15951333
TI  - Regulation of human pulmonary surfactant protein gene expression by 1alpha,25
      dihydroxyvitamin D3.
AB  - 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] has been reported to stimulate
      lung maturity, alveolar type II cell differentiation, and pulmonary surfactant
      synthesis in rat lung. We hypothesized that 1,25(OH)(2)D(3) stimulates expression
      of surfactant protein-A (SP-A), SP-B, and SP-C in human fetal lung and type II
      cells. We found that immunoreactive vitamin D receptor was detectable in fetal
      lung tissue and type II cells only when incubated with 1,25(OH)(2)D(3).
      1,25(OH)(2)D(3) significantly decreased SP-A mRNA in human fetal lung tissue but
      did not significantly decrease SP-A protein in the tissue. In type II cells,
      1,25(OH)(2)D(3) alone had no significant effect on SP-A mRNA or protein levels
      but reduced SP-A mRNA and protein in a dose-dependent manner when the cells were
      incubated with cAMP. SP-A mRNA levels in NCI-H441 cells, a nonciliated
      bronchiolar epithelial (Clara) cell line, were decreased in a dose-dependent
      manner in the absence or presence of cAMP. 1,25(OH)(2)D(3) had no significant
      effect on SP-B mRNA levels in lung tissue but increased SP-B mRNA and protein
      levels in type II cells incubated in the absence or presence of cAMP. Expression
      of SP-C mRNA was unaffected by 1,25(OH)(2)D(3) in lung tissue incubated +/- cAMP.
      These results suggest that regulation of surfactant protein gene expression in
      human lung and type II cells by 1,25(OH)(2)D(3) is not coordinated;
      1,25(OH)(2)D(3) decreases SP-A mRNA and protein levels in both fetal lung tissue
      and type II cells, increases SP-B mRNA and protein levels only in type II cells,
      and has no effect on SP-C mRNA levels.

PMID- 15951334
TI  - Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon
      nanotubes in mice.
AB  - Single-walled carbon nanotubes (SWCNT) are new materials of emerging
      technological importance. As SWCNT are introduced into the life cycle of
      commercial products, their effects on human health and environment should be
      addressed. We demonstrated that pharyngeal aspiration of SWCNT elicited unusual
      pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation
      with early onset yet progressive fibrosis and granulomas. A dose-dependent
      increase in the protein, LDH, and gamma-glutamyl transferase activities in
      bronchoalveolar lavage were found along with accumulation of 4-hydroxynonenal
      (oxidative biomarker) and depletion of glutathione in lungs. An early neutrophils
      accumulation (day 1), followed by lymphocyte (day 3) and macrophage (day 7)
      influx, was accompanied by early elevation of proinflammatory cytokines (TNF
      alpha, IL-1beta; day 1) followed by fibrogenic transforming growth factor (TGF)
      beta1 (peaked on day 7). A rapid progressive fibrosis found in mice exhibited two
      distinct morphologies: 1) SWCNT-induced granulomas mainly associated with
      hypertrophied epithelial cells surrounding SWCNT aggregates and 2) diffuse
      interstitial fibrosis and alveolar wall thickening likely associated with
      dispersed SWCNT. In vitro exposure of murine RAW 264.7 macrophages to SWCNT
      triggered TGF-beta1 production similarly to zymosan but generated less TNF-alpha
      and IL-1beta. SWCNT did not cause superoxide or NO.production, active SWCNT
      engulfment, or apoptosis in RAW 264.7 macrophages. Functional respiratory
      deficiencies and decreased bacterial clearance (Listeria monocytogenes) were
      found in mice treated with SWCNT. Equal doses of ultrafine carbon black particles
      or fine crystalline silica (SiO2) did not induce granulomas or alveolar wall
      thickening and caused a significantly weaker pulmonary inflammation and damage.

PMID- 15951335
TI  - Maturation of guinea pig tracheal strip stiffness.
AB  - Previously, we showed the shortening velocity of guinea pig tracheal strips was
      the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult
      animals (3-mo-old). The greatest shortening velocity was associated with the
      least resistance to shortening calculated from force-velocity curves among the
      three age groups. It remained to be verified if the stiffness of tracheal tissue,
      a measure of tissue response to geometrical deformations, is different among the
      three age groups. We hypothesized that stiffness of intact tracheal strips is
      lowest in the juvenile group and that this can explain the ontogeny of airway
      smooth muscle resistance to shortening and shortening velocity. Static stiffness
      measured through stepwise deformations showed no age-related differences.
      Evaluation of tissue response to oscillatory deformations showed that the dynamic
      stiffness of unstimulated tracheal strips was 8.35 +/- 0.88, 4.15 +/- 1.09, and
      8.21 +/- 1.57 kPa, and the phase angle was 10.3 +/- 2.93, 2.46 +/- 0.67, and 7.87
      +/- 1.77 degrees in infant, juvenile, and adult, respectively. Unstimulated
      juvenile strips were significantly lower in dynamic stiffness and phase angle
      compared with unstimulated infant or adult strips. This maturational profile was
      independent of muscle strip preset length or oscillation mode/amplitude but was
      abolished at peak of contraction to either carbachol or electric field
      stimulation. These results suggest that the noncontractile components of tracheal
      strips are less stiff and contain fewer viscous/frictional elements in juvenile
      than in other age groups. This may provide a functional basis for reduced
      resistance to length changes in juvenile airway smooth muscle.

PMID- 15951336
TI  - Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid
      in LPS-induced acute lung injury.
AB  - Infiltration of activated neutrophils [polymorphonuclear leukocytes (PMN)] into
      the lung is an important component of the inflammatory response in acute lung
      injury. The signals required to direct PMN into the different compartments of the
      lung have not been fully elucidated. In a murine model of LPS-induced lung
      injury, we investigated the sequential recruitment of PMN into the pulmonary
      vasculature, lung interstitium, and alveolar space. Mice were exposed to
      aerosolized LPS and bronchoalveolar lavage fluid (BAL), and lungs were harvested
      at different time points. We developed a flow cytometry-based technique to assess
      in vivo trafficking of PMN in the intravascular and extravascular lung
      compartments. Aerosolized LPS induced consistent PMN migration into all lung
      compartments. We found that sequestration in the pulmonary vasculature occurred
      within the first hour. Transendothelial migration into the interstitial space
      started 1 h after LPS exposure and increased continuously until a plateau was
      reached between 12 and 24 h. Transepithelial migration into the alveolar air
      space was delayed, as the first PMN did not appear until 2 h after LPS, reaching
      a peak at 24 h. Transendothelial migration and transepithelial migration were
      inhibited by pertussis toxin, indicating involvement of Galphai-coupled
      receptors. These findings confirm LPS-induced migration of PMN into the lung. For
      the first time, distinct transmigration steps into the different lung
      compartments are characterized in vivo.

PMID- 15951337
TI  - Congenital heart defects and genetic variants in the methylenetetrahydroflate
      reductase gene.
AB  - BACKGROUND: Most non-syndromic congenital heart defects (CHD) are caused by a
      complex interaction between maternal lifestyle factors, environmental exposures,
      and maternal and fetal genetic variants. Maternal periconceptional intake of
      folic acid containing vitamin supplements is reported to decrease the risk of
      CHD. The 677C-->T and 1298A-->C polymorphisms in the methylenetetrahydrofolate
      reductase (MTHFR) gene decrease enzyme activity. OBJECTIVE: To examine the
      relation between CHD and maternal and fetal MTHFR polymorphisms. METHODS: 375
      nuclear families were studied. The transmission/disequilibrium test was used to
      test for transmission distortion in complete triads. A log-linear approach was
      used to test for associations between CHD and maternal and offspring
      polymorphisms, and to estimate independently the contributions of maternal and
      fetal variants to relative risks. Haplotype frequencies were estimated and a
      haplotype transmission disequilibrium test carried out. RESULTS: The 1298C allele
      was transmitted less often than expected (p = 0.0013). There was no distortion in
      the transmission of the 677T allele, neither was there evidence of a parent of
      origin effect in the transmission of either of the single nucleotide
      polymorphisms. The 677C-1298C haplotype was also transmitted less often than
      expected (p = 0.0020). The relative risk associated with inheriting one copy of
      the 1298C allele was 0.64 (95% confidence interval, 0.48 to 0.87) and the that
      associated with inheriting two copies of the 1298C allele, 0.38 (0.21 to 0.70).
      CONCLUSIONS: The apparent protective effect of the MTHFR 1298C allele against CHD
      could have several explanations and further study is needed.

PMID- 15951338
TI  - Frequency-dependent baroreflex modulation of blood pressure and heart rate
      variability in conscious mice.
AB  - The goal of this study was to determine the baroreflex influence on systolic
      arterial pressure (SAP) and pulse interval (PI) variability in conscious mice.
      SAP and PI were measured in C57Bl/6J mice subjected to sinoaortic deafferentation
      (SAD, n = 21) or sham surgery (n = 20). Average SAP and PI did not differ in SAD
      or control mice. In contrast, SAP variance was enhanced (21 +/- 4 vs. 9.5 +/- 1
      mmHg2) and PI variance reduced (8.8 +/- 2 vs. 26 +/- 6 ms2) in SAD vs. control
      mice. High-frequency (HF: 1-5 Hz) SAP variability quantified by spectral analysis
      was greater in SAD (8.5 +/- 2.0 mmHg2) compared with control (2.5 +/- 0.2 mmHg2)
      mice, whereas low-frequency (LF: 0.1-1 Hz) SAP variability did not differ between
      the groups. Conversely, LF PI variability was markedly reduced in SAD mice (0.5
      +/- 0.1 vs. 10.8 +/- 3.4 ms2). LF oscillations in SAP and PI were coherent in
      control mice (coherence = 0.68 +/- 0.05), with changes in SAP leading changes in
      PI (phase = -1.41 +/- 0.06 radians), but were not coherent in SAD mice (coherence
      = 0.08 +/- 0.03). Blockade of parasympathetic drive with atropine decreased
      average PI, PI variance, and LF and HF PI variability in control (n = 10) but had
      no effect in SAD (n = 6) mice. In control mice, blockade of sympathetic cardiac
      receptors with propranolol increased average PI and decreased PI variance and LF
      PI variability (n = 6). In SAD mice, propranolol increased average PI (n = 6). In
      conclusion, baroreflex modulation of PI contributes to LF, but not HF PI
      variability, and is mediated by both sympathetic and parasympathetic drives in
      conscious mice.

PMID- 15951339
TI  - Renal vascular response to static handgrip exercise: sympathetic vs.
      autoregulatory control.
AB  - Static exercise causes activation of the sympathetic nervous system, which
      results in increased blood pressure (BP) and renal vascular resistance (RVR). The
      question arises as to whether renal vasoconstriction that occurs during static
      exercise is due to sympathetic activation and/or related to a pressure-dependent
      renal autoregulatory mechanism. To address this issue, we monitored renal blood
      flow velocity (RBV) responses to two different handgrip (HG) exercise paradigms
      in 7 kidney transplant recipients (RTX) and 11 age-matched healthy control
      subjects. Transplanted kidneys are functionally denervated. Beat-by-beat analyses
      of changes in RBV (observed via duplex ultrasound), BP, and heart rate were
      performed during HG exercise in all subjects. An index of RVR was calculated as
      BP/RBV. In protocol 1, fatiguing HG exercise (40% of maximum voluntary
      contraction) led to significant increases in RVR in both groups. However, at the
      end of exercise, RVR was more than fourfold higher in control subjects than in
      the RTX group (88 vs. 20% increase over baseline; interaction, P < 0.001). In
      protocol 2, short bouts of HG exercise (15 s) led to significant increases in RVR
      at higher workloads (50 and 70% of maximum voluntary contraction) in the control
      subjects (P < 0.001). RVR did not increase in the RTX group. In conclusion, we
      observed grossly attenuated renal vasoconstrictor responses to exercise in RTX
      subjects, in whom transplanted kidneys were considered functionally denervated.
      Our results suggest that renal vasoconstrictor responses to exercise in conscious
      humans are mainly dependent on activation of a neural mechanism.

PMID- 15951340
TI  - Frequency-dependent regulation of cardiac Na(+)/Ca(2+) exchanger.
AB  - The activity of the cardiac Na(+)/Ca(2+) exchanger (NCX1.1) undergoes continuous
      modulation during the contraction-relaxation cycle because of the accompanying
      changes in the electrochemical gradients for Na(+) and Ca(2+). In addition,
      NCX1.1 activity is also modulated via secondary, ionic regulatory mechanisms
      mediated by Na(+) and Ca(2+). In an effort to evaluate how ionic regulation
      influences exchange activity under pulsatile conditions, we studied the behavior
      of the cloned NCX1.1 during frequency-controlled changes in intracellular Na(+)
      and Ca(+) (Na(i)(+) and Ca(i)(2+)). Na(+)/Ca(2+) exchange activity was measured
      by the giant excised patch-clamp technique with conditions chosen to maximize the
      extent of Na(+)- and Ca(2+)-dependent ionic regulation so that the effects of
      variables such as pulse frequency and duration could be optimally discerned. We
      demonstrate that increasing the frequency or duration of solution pulses leads to
      a progressive decline in pure outward, but not pure inward, Na(+)/Ca(2+) exchange
      current. However, when the exchanger is permitted to alternate between inward and
      outward transport modes, both current modes exhibit substantial levels of
      inactivation. Changes in regulatory Ca(2+), or exposure of patches to limited
      proteolysis by alpha-chymotrypsin, reveal that this "coupling" is due to Na(+)
      dependent inactivation originating from the outward current mode. Under
      physiological ionic conditions, however, evidence for modulation of exchange
      currents by Na(i)(+)-dependent inactivation was not apparent. The current
      approach provides a novel means for assessment of Na(+)/Ca(2+) exchange ionic
      regulation that may ultimately prove useful in understanding its role under
      physiological and pathophysiological conditions.

PMID- 15951341
TI  - GH-releasing peptides improve cardiac dysfunction and cachexia and suppress
      stress-related hormones and cardiomyocyte apoptosis in rats with heart failure.
AB  - Growth hormone (GH)-releasing peptides (GHRP), a class of synthetic peptidyl GH
      secretagogues, have been reported to exert a cardioprotective effect on cardiac
      ischemia. However, whether GHRP have a beneficial effect on chronic heart failure
      (CHF) is unclear, and the present work aims to clarify this issue. At 9 wk after
      pressure-overload CHF was created by abdominal aortic banding in rats, one of
      four variants of GHRP (GHRP-1, -2, and -6 and hexarelin, 100 mug/kg) or saline
      was injected subcutaneously twice a day for 3 wk. Echocardiography and cardiac
      catheterization were performed to monitor cardiac function and obtain blood
      samples for hormone assay. GHRP treatment significantly improved left ventricular
      (LV) function and remodeling in CHF rats, as indicated by increased LV ejection
      fraction, LV end-systolic pressure, and diastolic posterior wall thickness and
      decreased LV end-diastolic pressure and LV end-diastolic dimension. GHRP also
      significantly alleviated development of cardiac cachexia, as shown by increases
      in body weight and tibial length in CHF rats. Plasma CA, renin, ANG II,
      aldosterone, endothelin-1, and atrial natriuretic peptide were significantly
      elevated in CHF rats but were significantly decreased in GHRP-treated CHF rats.
      GHRP suppressed cardiomyocyte apoptosis and increased cardiac GH secretagogue
      receptor mRNA expression in CHF rats. GHRP also decreased myocardial creatine
      kinase release in hypophysectomized rats subjected to acute myocardial ischemia.
      We conclude that chronic administration of GHRP alleviates LV dysfunction,
      pathological remodeling, and cardiac cachexia in CHF rats, at least in part by
      suppressing stress-induced neurohormonal activations and cardiomyocyte apoptosis.

PMID- 15951342
TI  - Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the
      mas receptor.
AB  - Peptide hormones such as ANG II and endothelin contribute to cardiac remodeling
      after myocardial infarction by stimulating myocyte hypertrophy and myofibroblast
      proliferation. In contrast, angiotensin-(1-7) [ANG-(1-7)] infusion after
      myocardial infarction reduced myocyte size and attenuated ventricular dysfunction
      and remodeling. We measured the effect of ANG-(1-7) on protein and DNA synthesis
      in cultured neonatal rat myocytes to assess the role of the heptapeptide in cell
      growth. ANG-(1-7) significantly attenuated either fetal bovine serum- or
      endothelin-1-stimulated [(3)H]leucine incorporation into myocytes with no effect
      on [(3)H]thymidine incorporation. [d-Ala(7)]-ANG-(1-7), the selective ANG type 1
      7 (AT(1-7)) receptor antagonist, blocked the ANG-(1-7)-mediated reduction in
      protein synthesis in cardiac myocytes, whereas the AT(1) and AT(2) angiotensin
      peptide receptors were ineffective. Serum-stimulated ERK1/ERK2 mitogen-activated
      protein kinase activity was significantly decreased by ANG-(1-7) in myocytes, a
      response that was also blocked by [d-Ala(7)]-ANG-(1-7). Both rat heart and
      cardiac myocytes express the mRNA for the mas receptor, and a 59-kDa
      immunoreactive protein was identified in both extracts of rat heart and cultured
      myocytes by Western blot hybridization with the use of an antibody to mas, an ANG
      (1-7) receptor. Transfection of cultured myocytes with an antisense
      oligonucleotide to the mas receptor blocked the ANG-(1-7)-mediated inhibition of
      serum-stimulated MAPK activation, whereas a sense oligonucleotide was
      ineffective. These results suggest that ANG-(1-7) reduces the growth of
      cardiomyocytes through activation of the mas receptor. Because ANG-(1-7) is
      elevated after treatment with angiotensin-converting enzyme inhibitors or AT(1)
      receptor blockers, ANG-(1-7) may contribute to their beneficial effects on
      cardiac dysfunction and ventricular remodeling after myocardial infarction.

PMID- 15951343
TI  - Positive inotropic and negative lusitropic effects of endothelin receptor agonism
      in vivo.
AB  - The endothelin (ET) system is involved in the regulation of myocardial function
      in health as well as in several diseases, such as congestive heart failure,
      myocardial infarction, and septic myocardial depression. Conflicting results have
      been reported regarding the acute contractile properties of ET-1. We therefore
      investigated the effects of intracoronary infusions of ET-1 and of the selective
      ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in
      anesthetized pigs. Myocardial effects were measured through analysis of the left
      ventricular pressure-volume relationship. ET-1 elicited increases in the
      myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to
      1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4
      +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment
      in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and
      t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for
      pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor
      dependent. In addition, intravenous administration of ET-1 impaired ventricular
      relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c
      administration caused impairments in left ventricular relaxation (tau from 43.3
      +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET
      1 elicits positive inotropic and negative lusitropic myocardial effects in a pig
      model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

PMID- 15951344
TI  - Protein kinase C epsilon induces systolic cardiac failure marked by exhausted
      inotropic reserve and intact Frank-Starling mechanism.
AB  - Myofilament dysfunction is a common point of convergence for many forms of heart
      failure. Recently, we showed that cardiac overexpression of PKC epsilon initially
      depresses myofilament activity and then leads to a progression of changes
      characteristic of human heart failure. Here, we examined the effects of PKC
      epsilon on contractile reserve, Starling mechanism, and myofilament activation in
      this model of end-stage dilated cardiomyopathy. Pressure-volume loop analysis and
      echocardiography showed that the PKC epsilon mice have markedly compromised
      systolic function and increased end-diastolic volumes. Dobutamine challenge
      resulted in a small increase in contractility in PKC epsilon mice but failed to
      enhance cardiac output. The PKC epsilon mice showed a normal length-dependent
      tension development in skinned cardiac muscle preparations, although Frank
      Starling mechanism appeared to be compromised in the intact animal. Simultaneous
      measurement of tension and ATPase demonstrated that the maximum tension and
      ATPase were markedly lower in the PKC epsilon mice at any length or Ca2+
      concentration. However, the tension cost was also lower indicating less energy
      expenditure. We conclude 1) that prolonged overexpression of PKC epsilon
      ultimately leads to a dilated cardiomyopathy marked by exhausted contractile
      reserve, 2) that PKC epsilon does not compromise the Frank-Starling mechanism at
      the myofilament level, and 3) that the Starling curve excursion is limited by the
      inotropic state of the heart. These results reflect the significance of the
      primary myofilament contractilopathy induced by phosphorylation and imply a role
      for PKC epsilon-mediated phosphorylation in myofilament physiology and the
      pathophysiology of decompensated cardiac failure.

PMID- 15951345
TI  - Impaired cardiac and sympathetic autonomic control in rats differing in
      acetylcholine receptor sensitivity.
AB  - Acetylcholine receptors (AChR) are important in premotor and efferent control of
      autonomic function; however, the extent to which cardiovascular function is
      affected by genetic variations in AChR sensitivity is unknown. We assessed heart
      rate variability (HRV) and baroreflex sensitivity (BRS) in rats bred for
      resistance (FRL) or sensitivity (FSL) to cholinergic agents compared with Sprague
      Dawley rats (SD), confirmed by using hypothermic responses evoked by the
      muscarinic agonist oxotremorine (0.2 mg/kg i.p.) (n > or = 9 rats/group).
      Arterial pressure, ECG, and splanchnic sympathetic (SNA) and phrenic (PNA) nerve
      activities were acquired under anesthesia (urethane 1.3 g/kg i.p.). HRV was
      assessed in time and frequency domains from short-term R-R interval data, and
      spontaneous heart rate BRS was obtained by using a sequence method at rest and
      after administration of atropine methylnitrate (mATR, 2 mg/kg i.v.). Heart rate
      and SNA baroreflex gains were assessed by using conventional pharmacological
      methods. FRL and FSL were normotensive but displayed elevated heart rates,
      reduced HRV and HF power, and spontaneous BRS compared with SD. mATR had no
      effect on these parameters in FRL or FSL, indicating reduced cardiovagal tone.
      FSL exhibited reduced PNA frequency, longer baroreflex latency, and reduced
      baroreflex gain of heart rate and SNA compared with FRL and SD, indicating in FSL
      dual impairment of cardiac and circulatory baroreflexes. These findings show that
      AChR resistance results in reduced cardiac muscarinic receptor function leading
      to cardiovagal insufficiency. In contrast, AChR sensitivity results in autonomic
      and respiratory abnormalities arising from alterations in central muscarinic and
      or other neurotransmitter receptors.

PMID- 15951346
TI  - Collagen and elastin cross-linking: a mechanism of constrictive remodeling after
      arterial injury.
AB  - Constrictive remodeling after arterial injury is related to collagen
      accumulation. Cross-linking has been shown to induce a scar process in cutaneous
      wound healing and is increased after arterial injury. We therefore evaluated the
      effect of cross-linking inhibition on qualitative and quantitative changes in
      collagen, elastin, and arterial remodeling after balloon injury in the
      atherosclerotic rabbit model. Atherosclerotic-like lesions were induced in
      femoral arteries of 28 New Zealand White rabbits by a combination of air
      desiccation and a high-cholesterol diet. After 1 mo, balloon angioplasty was
      performed in both femoral arteries. Fourteen rabbits were fed beta
      aminopropionitrile (beta-APN, 100 mg/kg) and compared with 14 untreated animals.
      The remodeling index, i.e., the ratio of external elastic lamina at the lesion
      site to external elastic lamina at the reference site, was determined 4 wk after
      angioplasty for both groups. Pyridinoline was significantly decreased in arteries
      from beta-APN-treated animals compared with controls, confirming inhibition of
      collagen cross-linking: 0.30 (SD 0.03) and 0.52 (SD 0.02) mmol/mol
      hydroxyproline, respectively (P = 0.002). Scanning and transmission electron
      microscopy showed a profound disorganization of collagen fibers in arteries from
      beta-APN-treated animals. The remodeling index was significantly higher in beta
      APN-treated than in control animals [1.1 (SD 0.3) vs. 0.8 (SD 0.3), P = 0.03],
      indicating favorable remodeling. Restenosis decreased by 33% in beta-APN-treated
      animals: 32% (SD 16) vs. 48% (SD 24) (P = 0.02). Neointimal collagen density was
      significantly lower in beta-APN-treated animals than in controls: 23.0% (SD 3.8)
      vs. 29.4% (SD 4.0) (P = 0.004). These findings suggest that collagen and elastin
      cross-linking plays a role in the healing process via constrictive remodeling and
      restenosis after balloon injury in the atherosclerotic rabbit model.

PMID- 15951347
TI  - Differential regulation of insulin resistance and hypertension by sex hormones in
      fructose-fed male rats.
AB  - Differences in gender are in part responsible for the development of insulin
      resistance (IR) and associated hypertension. Currently, it is unclear whether
      these differences are dictated by gender itself or by the relative changes in
      plasma estrogen and/or testosterone. We investigated the interrelationships
      between testosterone and estrogen in the progression of IR and hypertension in
      vivo in intact and gonadectomized fructose-fed male rats. Treatment with estrogen
      significantly reduced the testosterone levels in both normal chow-fed and
      fructose-fed rats. Interestingly, fructose feeding induced a relative increase in
      estradiol levels, which did not affect IR in both intact and gonadectomized
      fructose-fed rats. However, increasing the estrogen levels improved insulin
      sensitivity in both intact and gonadectomized fructose-fed rats. In intact males,
      fructose feeding increased the blood pressure (140 +/- 2 mmHg), which was
      prevented by estrogen treatment. However, the blood pressure in the fructose-fed
      estrogen rats (125 +/- 1 mmHg) was significantly higher than that of normal chow
      fed (113 +/- 1 mmHg) and fructose-fed gonadectomized rats. Estrogen treatment did
      not affect the blood pressure in gonadectomized fructose-fed rats (105 +/- 2
      mmHg). These data suggest the existence of a threshold value for estrogen below
      which insulin sensitivity is unaffected. The development of hypertension in this
      model is dictated solely by the presence or absence of testosterone. In summary,
      the development of IR and hypertension is governed not by gender per se but by
      the interactions of specific sex hormones such as estrogen and testosterone.

PMID- 15951348
TI  - Correlation between mRNA levels and functional role of alpha1-adrenoceptor
      subtypes in arteries: evidence of alpha1L as a functional isoform of the alpha1A
      adrenoceptor.
AB  - The mRNA levels for the three alpha1-adrenoceptor subtypes, alpha1A, alpha1B, and
      alpha1D, were quantified by real-time RT-PCR in arteries from Wistar rats. The
      alpha1D-adrenoceptor was prominent in both aorta (79.0%) and mesenteric artery
      (68.7%), alpha1A predominated in tail (61.7%) and small mesenteric artery
      (73.3%), and both alpha1A- and alpha1D-subtypes were expressed at similar levels
      in iliac artery. The mRNA levels of the alpha1B-subtype were a minority in all
      vessels (1.7-11.1%). Concentration-response curves of contraction in response to
      phenylephrine or relaxation in response to alpha1-adrenoceptor antagonists on
      maximal sustained contraction induced by phenylephrine were constructed from
      control vessels and vessels pretreated with 100 micromol/l chloroethylclonidine
      (CEC) for 30 min. The significant decrease in the phenylephrine potency observed
      after CEC treatment together with the inhibitory potency displayed by 8-{2-[4-(2
      methoxyphenyl)-1-piperazinyl]-8-azaspiro (4,5) decane-7-dionedihydrochloride}
      (BMY-7378, an alpha1D-adrenoceptor antagonist) confirm the relevant role of
      alpha1D-adrenoceptors in aorta and iliac and proximal mesenteric arteries. The
      potency of 5-methylurapidil (an alpha1A-adrenoceptor antagonist) and the changes
      in the potency of both BMY-7378 and 5-methylurapidil after CEC treatment provided
      evidence of a mixed population of alpha1A- and alpha1D-adrenoceptors in iliac and
      distal mesenteric arteries. The low potency of prazosin (pIC50 < 9) as well as
      the high 5-methylurapidil potency in tail and small mesenteric arteries suggest
      the main role of alpha1A/alpha1L-adrenoceptors with minor participation of the
      alpha1D-subtype. The mRNA levels and CEC treatment corroborated this pattern and
      confirmed that the alpha1L-adrenoceptor could be a functional isoform of the
      alpha1A-subtype.

PMID- 15951349
TI  - Reduced constrictor reactivity balances impaired vasodilation in the mesenteric
      circulation of the obese Zucker rat.
AB  - Obesity causes whole body insulin resistance and impaired vasodilation to nitric
      oxide (NO). Because NO is a major contributor to the regulation of mesenteric
      blood flow, the mesenteric circulation of obese animals is faced with reduced
      capacity to increase flow and increased demand for flow associated with elevated
      consumption of food. This study hypothesized that insulin resistance impairs NO
      mediated dilation but that constrictor reactivity would be reduced to compensate
      in obese animals. We further hypothesized that elevated superoxide levels caused
      impaired responses to NO in insulin resistance. Vasodilator reactivity and
      vasoconstrictor reactivity of mesenteric resistance arteries from lean (LZR) and
      obese (OZR) Zucker rats were examined in vitro using videomicroscopy. Insulin
      resistance independent of obesity was induced via fructose feeding in LZR (FF
      LZR). Endothelium-dependent NO-mediated dilation was reduced in OZR and FF-LZR
      compared with LZR. Impairments in NO-mediated dilation were reversed with 1 mM
      tempol, a SOD mimetic. Constrictor reactivity to norepinephrine was reduced in
      OZR but not in FF-LZR relative to LZR. Basal mesenteric vascular resistance was
      similar in LZR and OZR despite impaired NO-dependent dilation in OZR. Mesenteric
      vascular resistance was increased in FF-LZR relative to LZR. These data indicate
      that there is reduced constrictor reactivity in OZR that may offset the impaired
      NO-mediated dilation and preserve mesenteric blood flow in hyperphagic, obese
      animals.

PMID- 15951350
TI  - PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells.
AB  - Endothelial nitric oxide synthase (eNOS), VEGF, and hypoxia-inducible factor 1
      alpha (HIF-1alpha) are important regulators of endothelial function, which plays
      a role in the pathophysiology of heart failure (HF). PGE1 analog treatment in
      patients with HF elicits beneficial hemodynamic effects, but the precise
      mechanisms have not been investigated. We have investigated the effects of the
      PGE1 analog alprostadil on eNOS, VEGF, and HIF-1alpha expression in human
      umbilical vein endothelial cells (HUVEC) using RT-PCR and immunoblotting under
      normoxic and hypoxic conditions. In addition, we studied protein expression by
      immunohistochemical staining in explanted hearts from patients with end-stage HF,
      treated or untreated with systemic alprostadil. Alprostadil causes an
      upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases
      HIF-1alpha. Hypoxia potently increased eNOS, VEGF, and HIF-1alpha synthesis. The
      alprostadil-induced upregulation of eNOS and VEGF was prevented by inhibition of
      MAPKs with PD-98056 or U-0126. Consistently, the expression of eNOS and VEGF was
      increased, and HIF-1alpha was reduced in failing hearts treated with alprostadil.
      The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be
      useful for patients with HF where endothelial dysfunction is involved in the
      disease process.

PMID- 15951351
TI  - Neutrophil NADPH-oxidase activation by an annexin AI peptide is transduced by the
      formyl peptide receptor (FPR), whereas an inhibitory signal is generated
      independently of the FPR family receptors.
AB  - Truncation of the N-terminal part of the calcium-regulated and phospholipid
      binding protein annexin AI has been shown to change the functional properties of
      the protein and to generate immunoregulatory peptides. Proinflammatory as well as
      anti-inflammatory signals are triggered by these peptides, and the two formyl
      peptide receptor (FPR) family members expressed in neutrophils, FPR and FPR-like
      1 (FPRL1), have been suggested to transduce these signals. We now report that an
      annexin AI peptide (Ac9-25) activates, as well as inhibits, the neutrophil
      release of superoxide anions. Results obtained from experiments with receptor
      antagonists/inhibitors, desensitized cells, and transfected cells reveal that the
      Ac9-25 peptide activates the neutrophil reduced nicotinamide adenine dinucleotide
      phosphate oxidase through FPR but not through FPRL1. The Ac9-25 peptide also
      inhibits the oxidase activity in neutrophils triggered, not only by the FPR
      specific agonist N-formyl-Met-Leu-Phe but also by several other agonists
      operating through different G protein-coupled receptors. Our data show that the
      two signals generated by the Ac9-25 peptide are transmitted through different
      receptors, the inhibitory signal being transduced by a not-yet identified
      receptor distinct from FPR and FPRL1.

PMID- 15951352
TI  - IL-2 induces expression and secretion of IFN-gamma in murine peritoneal
      macrophages.
AB  - We investigated the effect of interleukin (IL)-2, a T cell growth factor capable
      of activating certain macrophage functions, on interferon (IFN)-gamma expression
      in resting mouse peritoneal macrophages (PM). IL-2 addition to PM from different
      mouse strains up-modulated IFN-gamma mRNA and protein secretion. It is notable
      that endogenous type I and II IFNs did not play any role in the IL-2-mediated
      effect, as comparable levels of secreted IFN-gamma were observed upon IL-2
      stimulation of PM from deficient mice. In contrast, endogenous IFN-gamma was
      requested for the IL-12-induced IFN-gamma production. It is interesting that
      blocking of each component of the IL-2 receptor (IL-2R) by neutralizing
      antibodies almost completely abolished IL-2-induced IFN-gamma production,
      suggesting that all IL-2R chains contribute to the PM biological response to IL
      2. The simultaneous treatment of PM with IL-2 and IL-12 resulted in a higher IFN
      gamma secretion with respect to that obtained upon treatment with IL-2 or IL-12
      alone. It is notable that IFN-gamma protein was expressed intracellularly in the
      majority of cells exhibiting a macrophage phenotype (i.e., F4/80+) and was
      secreted upon IL-2 stimulation. Overall, these findings demonstrate that IL-2
      regulates at different levels IFN-gamma expression in macrophages, highlighting
      the crucial role of these cells and their regulated responsiveness to key
      cytokines in the cross-talk between innate and adaptive immunity.

PMID- 15951353
TI  - In vitro activity of tigecycline against Bacteroides species.
AB  - OBJECTIVES: To ascertain the current susceptibility patterns of members of the
      Bacteroides fragilis group in our hospital and to assess the in vitro activity of
      tigecycline against these organisms. METHODS: A total of 400 non-duplicate
      clinical isolates of the B. fragilis group collected from 2000 to 2002 were
      studied. Susceptibility testing was performed according to the reference agar
      dilution method described by the NCCLS. The following antimicrobials were tested:
      tigecycline, clindamycin, metronidazole, chloramphenicol, cefoxitin, imipenem,
      amoxicillin-clavulanate and piperacillin-tazobactam. RESULTS: All strains were
      susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin,
      the overall susceptibility rates were 59.5% and 83%, respectively. Imipenem and
      piperacillin-tazobactam were the most active beta-lactam agents tested.
      Tigecycline inhibited 89.8% of the strains at a concentration of 8 mg/L with an
      MIC range of <or=0.01 to >16 mg/L. By comparing the MIC50 and MIC90 values of
      tigecycline among the various species of the group, B. fragilis, Bacteroides
      thetaiotaomicron and Bacteroides vulgatus were the most susceptible (MIC50/MIC90s
      of 0.5-1/8 mg/L). CONCLUSIONS: Tigecycline exhibited activity against most
      isolates of the B. fragilis group tested. These results indicate that tigecycline
      may be useful in the treatment and prophylaxis of infections involving these
      organisms.

PMID- 15951354
TI  - Diversity of thymidine analogue resistance genotypes among newly diagnosed HIV-1
      infected persons.
AB  - The introduction of highly active antiretroviral therapy (HAART) has resulted in
      a significant decrease in HIV and AIDS-related mortality and morbidity. However,
      these treatments can select for drug-resistant viruses which are associated with
      poor virological responses to the antiretroviral therapy and possible loss of
      clinical benefit. Drug-resistant viruses can also be transmitted between
      individuals. In the absence of drug pressure, transmitted drug-resistant viruses
      gradually lose resistance mutations that confer a selective disadvantage as they
      evolve to more fit viruses. As a result, unusual resistance-related genotypes not
      commonly seen in treated patients may arise in the population. Viruses with
      unique patterns of thymidine analogue-associated mutations (TAMs) have now been
      identified in a substantial proportion of treatment-naive recently diagnosed
      persons. In this leading article, I discuss these findings and the potential
      impact of these unique reverse transcriptase (RT) genotypes on evolution of
      resistance and treatment responses.

PMID- 15951355
TI  - The future role of the IEA.

PMID- 15951356
TI  - Beyond reproduction: women's health in today's developing world.
AB  - BACKGROUND: The concept of women's health is tethered strongly to reproductive
      health. At present, international attention and resources are focused on
      obstetric events and, recently, HIV/AIDS because of the significance of these
      problems in the least developed nations. This limited concept of women's health,
      however, is decreasingly relevant to the global community, and needs to be
      revisited in the light of decreasing fertility and increasing life expectancy in
      many countries where it was previously applicable. It should be expanded to
      embrace the full spectrum of health experienced by women, and preventive and
      remedial approaches to the major conditions that afflict women. Allocation of
      health service resources should be aligned with the epidemiological realities of
      these threats to women's health. METHODS: Cause of death data for women aged 15
      34 years and 35-44 years were examined for nine less developed countries. Deaths
      associated with pregnancy and child birth, and HIV were compared with deaths due
      to three chronic disease categories (cancer, cardiovascular disease, and
      diabetes). The women's health research literature for developing countries
      appearing in the American Journal of Public Health and British Medical Journal
      was also examined. RESULTS: In seven out of the nine countries, among women aged
      15-34 years, chronic diseases caused over 20% of deaths, while reproductive
      causes and HIV together accounted for approximately 10% of deaths, in all
      countries except in India. Among women aged 35-44 years, in all but India,
      chronic diseases accounted for over four times the deaths attributable to
      reproductive causes and HIV. The causes of death were not related to the level of
      development in these countries as measured by GNI PPP. Papers pertaining to
      women's health published in public health and medical research journals focused
      principally on reproduction. CONCLUSIONS: Extending the definition of women's
      health to include a concern for chronic diseases is critical if the needs of
      women in less developed nations are to be met. In less developed countries,
      chronic disease is the most important cause of female death even during
      childbearing years and for women with young families. Development agencies and
      private philanthropy must begin to fund the studies that will further refine our
      understanding of the role of chronic diseases in women's health in the developing
      world.

PMID- 15951357
TI  - Material hardship alters the diurnal rhythm of salivary cortisol.
AB  - BACKGROUND: In the quest for biological mechanisms underlying socioeconomic
      differences in health outcomes, attention has turned to the role of the
      hypothalamic-pituitary-adrenocortical axis. As there is some evidence that both
      acute and chronic stress raise cortisol levels, and material hardship is a
      stressor, we examined the relationship of chronic material hardship with salivary
      cortisol levels over the day. METHODS: The data are from a survey of a sample of
      poor women aged 18-54. Up to four repeated measures of salivary cortisol levels
      were obtained from 188 women in this sample and modelled as a diurnal profile.
      Self-reports of a variety of sources of material hardship over the preceding year
      were combined into a single scale. Specific dimensions of the subjects' cortisol
      profiles were compared across levels of material hardship. RESULTS: Salivary
      cortisol varied over the day, and by level of reported material hardship. Upon
      awakening, salivary cortisol levels were comparable across hardship levels. But
      soon after waking, women at low levels of hardship experienced both a
      significantly sharper morning surge and subsequently a sharper decline in
      salivary cortisol (16.0 and 29.5 nmol/l/h) than women with high hardship levels
      (5.9 and 24.3 nmol/l/h). These differences in cortisol diurnal pattern tended to
      be related in a dose-response way to levels of material hardship. CONCLUSIONS:
      Material hardship among poor women is associated with changes in the diurnal
      rhythms of cortisol, particularly in the waking response, which is blunted in
      women with high levels of hardship.

PMID- 15951358
TI  - Cohort Profile: The Mater-University of Queensland Study of Pregnancy (MUSP).

PMID- 15951359
TI  - Vaccination history and risk of childhood leukaemia.
AB  - BACKGROUND: Previous studies on vaccination and childhood leukaemia generated
      inconsistent results. METHODS: In the Northern California Childhood Leukaemia
      Study, a case-control study with incident cases and matched birth certificate
      controls, detailed written vaccination records were collected. A total of 323
      cases aged 0-14 years at diagnosis and 409 controls were included in this
      analysis. All vaccinations were censored on the reference date (date of diagnosis
      for cases and the corresponding date for matched controls). Conditional logistic
      regression analysis was conducted, adjusting for potential confounding factors. A
      primary variable of interest is the number of administrations (doses) of various
      types of vaccines. RESULTS: Vaccinations against diphtheria, pertussis, tetanus,
      poliomyelitis, measles, mumps, and rubella were not associated with the risk of
      leukaemia. The odds ratio for each dose of Haemophilus influenzae type b (Hib)
      vaccine was 0.81 (95% CI 0.68-0.96). Compared with children who received two or
      fewer doses of Hib vaccine, those who received three or more doses had a
      significantly reduced risk of childhood leukaemia (odds ratio = 0.55, 95%
      confidence interval 0.32-0.94). The number of doses of hepatitis B vaccine
      received was not associated with leukaemia risk. CONCLUSIONS: Hib vaccination is
      associated with a reduced risk of childhood leukaemia. Future studies with
      detailed exposure assessment and large sample sizes are needed to further address
      the role of vaccinations in the etiology of childhood leukaemia.

PMID- 15951360
TI  - Development and validation of a self-report measure of emotional intelligence as
      a multidimensional trait domain.
AB  - Psychometric review of 33 peer-reviewed studies of six self-report emotional
      intelligence (EI) measures supports a multidimensional conceptualization of EI.
      The nature and number of EI facets, however, and their distinctiveness from more
      established trait domains is unclear. Building on earlier efforts, three studies
      were undertaken (Ns = 138, 163, 152) to develop self-report measures of 10 facets
      of EI proposed by Salovey and Mayer (1990). Results support the reliability
      (internal consistency, test-retest) and validity (content, criterion, construct,
      structural) of the proposed scales and their distinctiveness among themselves and
      with respect to more established trait domains (e.g., personality). Specifically,
      three satisfaction and four cross-cultural adaptability facets were predicted
      uniquely by 9 of the 10 proposed subscales, controlling for social desirability,
      the Big Five, positive and negative affect, and self-monitoring. All told,
      results confirm that trait-EI can be measured using self-report and
      conceptualized as a distinct multidimensional domain.

PMID- 15951361
TI  - Attributional inference across cultures: similar automatic attributions and
      different controlled corrections.
AB  - Five studies examined the automatic and controlled components of attributional
      inference in U.S. and East Asian (EA) samples. Studies 1 through 3 used
      variations of the "anxious woman" paradigm, manipulating the inferential goal
      (dispositional or situational) and the normative impact of situational constraint
      information (discounting or augmenting). In each study, U.S. and EA participants
      under cognitive load produced strong automatic attributions to the focus of their
      inferential goal (dispositional or situational). Compared with the U.S. cognitive
      load participants, U.S. no load participants corrected their attributions
      according to the normative rules of inference. In contrast, EA no load
      participants corrected in the direction of situational causality, even when the
      specific content of the situational information provided should have promoted
      stronger dispositional inferences. Studies 4 and 5 examined and ruled out
      alternative accounts. Results are discussed in terms of a situational causality
      heuristic present in EA individuals.

PMID- 15951362
TI  - Implementation intentions, perfectionism, and goal progress: perhaps the road to
      hell is paved with good intentions.
AB  - Two studies explored whether perfectionism moderates the impact of implementation
      intentions on goal progress. Study 1 used an implementation intention
      manipulation to examine the effects of these plans in interaction with
      perfectionism on the progress of New Year's resolutions. Study 2 added a repeated
      implementation intention condition and monitored affect and monthly goal
      progress. The results of both studies revealed a significant backfire effect of
      the implementation intentions on goal progress for participants high on a
      particular dimension of perfectionism (socially prescribed perfectionism). These
      perfectionists reported doing significantly worse at reaching their personal
      goals when they were asked to formulate implementation intentions than when they
      completed a control exercise. There also was evidence that implementation
      planning aroused negative affect for socially prescribed perfectionists. These
      results are the first to suggest that implementation planning may be contra
      indicated for individuals with self-critical tendencies.

PMID- 15951363
TI  - Perfectionism, academic motivation, and psychological adjustment: an integrative
      model.
AB  - The purpose of this article was to propose and test an integrative model on the
      role of perfectionism, academic motivation, and psychological adjustment
      difficulties in undergraduate students. The model posits that self-oriented
      perfectionism facilitates self-determined academic motivation, whereas socially
      prescribed perfectionism enhances non-self-determined academic motivation. In
      turn, self-determined and non-self-determined academic motivations, respectively,
      lead to lower and higher levels of psychological adjustment difficulties. Results
      from two studies using structural equation modeling analyses provided support for
      the model.

PMID- 15951364
TI  - Culture and diverging views of social events.
AB  - The authors compared East Asians' and Americans' views of everyday social events.
      Research suggests that Americans tend to focus more on the self and to have a
      greater sense of personal agency than East Asians. The authors assessed whether,
      compared to East Asians, Americans emphasize main characters even when events do
      not involve the self and whether they see more agency or intentionality in
      actions, even when the actions are not their own. Whether East Asians would
      observe more emotions in everyday scenarios than would Americans also was
      investigated. In Study 1, Chinese and Americans read alleged diary entries of
      another person. Americans did focus more on main characters and on characters'
      intentionality. Study 2 replicated these results comparing Taiwanese and
      Americans on free recall of events concerning the self and of narratives and
      videos concerning others. Study 2 also found that Taiwanese made more comments
      about the emotional states of characters.

PMID- 15951365
TI  - The role of affect in determining the attributional weight of immoral behaviors.
AB  - Theories about why immoral behaviors carry a large amount of attributional weight
      tend to emphasize traditional cognitive variables. In contrast, the authors
      propose that the degree of negative affect that these behaviors induce in
      observers is largely responsible for their attributional weight. Studies 1 and 2
      demonstrate an association between the amount of negative affect induced by
      immoral behaviors and their attributional weight. Studies 3 and 4 provide causal
      evidence for this idea by either "adding in" or "taking away" the negative affect
      associated with immoral behaviors to influence their attributional weight.
      Finally, Study 5 demonstrates that negative affect can be induced through a
      variety of negative emotions (disgust, sadness, and fear), with similar results.
      It is argued that it is difficult to account for these data solely on the basis
      of traditional cognitive variables, and so a theory that includes an emphasis on
      affect as a causal variable is desirable.

PMID- 15951366
TI  - Attitude importance as a moderator of the relationship between implicit and
      explicit attitude measures.
AB  - The authors examined attitude importance as a moderator of the relationship
      between the Implicit Association Test (IAT) and explicit attitude measures. In
      Study 1 (N = 194), as ratings of attitude importance regarding the 2000
      presidential election increased, the strength of the relationship between a Bush
      Gore IAT and explicit attitude measures also increased. Study 2 provided a
      conceptual replication of these results using attitudes toward Coke and Pepsi (N
      = 112). In addition, across both studies, explicit attitude measures were better
      predictors of deliberative behaviors than IAT scores. In Study 3 (N = 77), the
      authors examined the role of elaboration as a mechanism by which attitude
      importance may moderate IAT-explicit attitude correlations. As predicted,
      increased elaboration resulted in stronger IAT-explicit attitude correlations.
      Other possible mechanisms by which attitude importance may moderate the IAT
      explicit attitude relationship also are discussed.

PMID- 15951367
TI  - Sexual victimization in relation to perceptions of risk: mediation,
      generalization, and temporal stability.
AB  - There is evidence that personal experience with trauma is associated with
      increases in both personal and comparative risk perception. This study
      investigates this relation in terms of sexual victimization among women, focusing
      on three potential mediators: perceived control over sexual assault, perceived
      similarity to a typical sexual assault victim, and psychological distress.
      Mediational analyses were investigated using structural equation modeling.
      Although victimization experience was not related to comparative risk perception,
      it was associated with greater personal risk perception. This relation was
      mediated by perceived similarity to a typical sexual assault victim. Prospective
      analyses indicated that personal risk perception does change in response to
      sexual victimization but also indicated that heightened risk perception may be an
      accurate assessment of risk that actually precedes victimization experience.
      Implications for the meaning of perceived similarity and perceptions of risk for
      sexual assault victims are discussed.

PMID- 15951368
TI  - Giving advice or making decisions in someone else's place: the influence of
      impression, defense, and accuracy motivation on the search for new information.
AB  - When making decisions, people have been found predominantly to seek information
      supporting their preferred choice and to neglect conflicting information. In this
      article, the authors investigate to what extent different types of advisors, who
      recommend a choice to someone or make a decision on behalf of someone, show the
      same confirmatory information search. In Experiment 1, the authors presented
      participants, in the role of advisors, with a client's decision problem and found
      that when making a recommendation, advisors conducted a more balanced information
      search than participants who were making a decision for themselves. However,
      advisors who had to make a decision on behalf of their clients revealed an
      increased preference for information supporting their position. Experiment 2
      suggested that this confirmatory information search was caused by impression
      motivation: The advisors bolstered their decision to justify it to the client.
      The results are discussed within the multiple motive framework of the heuristic
      systematic model.

PMID- 15951369
TI  - Effective leadership in salient groups: revisiting leader-member exchange theory
      from the perspective of the social identity theory of leadership.
AB  - Two studies compared leader-member exchange (LMX) theory and the social identity
      theory of leadership. Study 1 surveyed 439 employees of organizations in Wales,
      measuring work group salience, leader-member relations, and perceived leadership
      effectiveness. Study 2 surveyed 128 members of organizations in India, measuring
      identification not salience and also individualism/collectivism. Both studies
      provided good support for social identity predictions. Depersonalized leader
      member relations were associated with greater leadership effectiveness among high
      than low-salient groups (Study 1) and among high than low identifiers (Study 2).
      Personalized leadership effectiveness was less affected by salience (Study 1) and
      unaffected by identification (Study 2). Low-salience groups preferred
      personalized leadership more than did high-salience groups (Study 1). Low
      identifiers showed no preference but high identifiers preferred depersonalized
      leadership (Study 2). In Study 2, collectivists did not prefer depersonalized as
      opposed to personalized leadership, whereas individualists did, probably because
      collectivists focus more on the relational self.

PMID- 15951370
TI  - Modulation of the oligomerization of isolated ryanodine receptors by their
      functional states.
AB  - The calcium release channels/ryanodine receptors (RyRs) usually form two
      dimensional regular lattices in the endoplasmic/sarcoplasmic reticulum membranes.
      However, the function and modulation of the interaction between neighboring RyRs
      are still unknown. Here, with an in vitro aqueous system, we demonstrate that the
      interaction between RyRs isolated from skeletal muscle (RyR1s) is modulated by
      their functional states by using photon correlation spectroscopy and
      [(3)H]ryanodine binding assay. High level of oligomerization is observed for
      resting closed RyR1s with nanomolar Ca(2+) in solution. Activation of RyR1s by
      micromolar Ca(2+) or/and millimolar AMP leads to the de-oligomerization of RyR1s.
      The oligomerization of RyR1s remains at high level when RyR1s are stabilized at
      closed state by Mg(2+). The modulation of RyR1-RyR1 interaction by the functional
      state is also observed under near-physiological conditions, suggesting that the
      interaction between arrayed RyR1s would be dynamically modulated during
      excitation-contraction coupling. These findings provide exciting new information
      to understand the function and operating mechanism of RyR arrays.

PMID- 15951371
TI  - Response to comment by Almeida et al.: free area theories for lipid bilayers-
      predictive or not?
AB  - Free area theories for lateral diffusion in lipid bilayers are reviewed and
      discussed. It has been suggested by Almeida et al. that free area theories yield
      quantitative predictions for lateral diffusion coefficients of lipids. We
      investigate the plausibility of this suggestion by first sketching what is to be
      expected of a quantitative theory with predictive power, and subsequently
      examining whether existing free area theories comply with these expectations. Our
      conclusion is that current free area theories for lipid bilayers are not
      quantitative theories with predictive power. They involve a number of adjustable
      parameters, all of which are not estimated independently, but derived from
      fitting the theory to the very data whose behavior the theory is supposed to
      predict. Further, the interpretation and behavior of some of the parameters are
      ambiguous. The best example is the so-called activation barrier, whose
      qualitative behavior with the cholesterol concentration in a DMPC bilayer varies
      depending on the experimental method used to generate the input data and the
      exact assumptions made to formulate the theory. Independent determination of the
      activation barrier from numerical simulations or experiments appears to be very
      difficult.

PMID- 15951372
TI  - Cell motility as persistent random motion: theories from experiments.
AB  - Experimental time series for trajectories of motile cells may contain so much
      information that a systematic analysis will yield cell-type-specific motility
      models. Here we demonstrate how, using human keratinocytes and fibroblasts as
      examples. The two resulting models reflect the cells' different roles in the
      organism, it seems, and show that a cell has a memory of past velocities. They
      also suggest how to distinguish quantitatively between various surfaces'
      compatibility with the two cell types.

PMID- 15951373
TI  - Cross talk free fluorescence cross correlation spectroscopy in live cells.
AB  - Fluorescence correlation spectroscopy (FCS) is now a widely used technique to
      measure small ensembles of labeled biomolecules with single molecule detection
      sensitivity (e.g., low endogenous concentrations). Fluorescence cross correlation
      spectroscopy (FCCS) is a derivative of this technique that detects the
      synchronous movement of two biomolecules with different fluorescence labels. Both
      methods can be applied to live cells and, therefore, can be used to address a
      variety of unsolved questions in cell biology. Applications of FCCS with
      autofluorescent proteins (AFPs) have been hampered so far by cross talk between
      the detector channels due to the large spectral overlap of the fluorophores. Here
      we present a new method that combines advantages of these techniques to analyze
      binding behavior of proteins in live cells. To achieve this, we have used dual
      color excitation of a common pair of AFPs, ECFP and EYFP, being discriminated in
      excitation rather than in emission. This is made possible by pulsed excitation
      and detection on a shorter timescale compared to the average residence time of
      particles in the FCS volume element. By this technique we were able to eliminate
      cross talk in the detector channels and obtain an undisturbed cross correlation
      signal. The setup was tested with ECFP/EYFP lysates as well as chimeras as
      negative and positive controls and demonstrated to work in live HeLa cells
      coexpressing the two fusion proteins ECFP-connexin and EYFP-connexin.

PMID- 15951374
TI  - Mechanical studies of single ribosome/mRNA complexes.
AB  - Methodology was developed for specifically anchoring Escherichia coli 70S
      ribosomes onto a chemically modified, cysteine-reactive glass surface.
      Immobilized ribosomes maintain the capability of binding a polyuridylic acid
      (poly(U)) template, enabling investigation of mechanical properties of individual
      ribosome-poly(U) complexes using laser tweezers. Streptavidin-coated polystyrene
      microspheres bound specifically to the biotinylated 3' end of long (up to 10,000
      bases) poly(U) strands. A novel optical method was built to control the position
      of the laser trap along the microscope optical axis at 2 nm resolution,
      facilitating measurement of the force-extension relationship for poly(U). Some
      immobilized ribosome-poly(U) complexes supported 100 pN of force applied at the
      3' end of the mRNA. Binding of N-acetylated Phe-tRNA(Phe), an analog of the
      initiator fMet-tRNA(Met), enhanced the population of complexes that could
      withstand high forces. The persistence length of poly(U) RNA homopolymer, modeled
      as a worm-like chain, was found to be 0.79 +/- 0.05 nm and the backbone
      elasticity was 900 +/- 140 pN, similar to values for single-stranded DNA.

PMID- 15951375
TI  - Optical measurement of surface tension in a miniaturized air-liquid interface and
      its application in lung physiology.
AB  - We have previously shown that lamellar body-like particles, the form in which
      pulmonary surfactant is secreted, spontaneously disintegrate when they contact an
      air-liquid interface, eventually creating an interfacial film. Here, we combined
      these studies with a new technique enabling the simultaneous and non-invasive
      measurement of surface tension (gamma). This method is a refinement of the
      pendant-drop principle. A sapphire cone with a 300-microm aperture keeps the
      experimental fluid by virtue of surface coherence in a fixed and nearly planar
      position above the objective of an inverted microscope. The radius of curvature
      of the fluid meniscus is related to gamma and determines the pattern of light
      back-reflection upon epi-illumination. This method, which we name "inverted
      interface", has several novel aspects, in particular its microscopic dimensions.
      When using lamellar body-like particles freshly released by alveolar type II
      cells, we found that their conversion at the interface resulted in gamma
      reduction close to 30 mN/m. After a fast initial decay, gamma-decrease proceeded
      slowly and in proportion to single particle conversions. These conversions ceased
      with time whereas gamma decreased further, probably due to reorganization of the
      already deposited material. The present investigation indicates that surface film
      formation by adsorption of large surfactant aggregates is an important mechanism
      by which gamma is reduced in the lung.

PMID- 15951376
TI  - A homology model of the pore region of HCN channels.
AB  - HCN channels are activated by membrane hyperpolarization and regulated by cyclic
      nucleotides, such as cyclic adenosine-mono-phosphate (cAMP). Here we present
      structural models of the pore region of these channels obtained by using homology
      modeling and validated against spatial constraints derived from
      electrophysiological experiments. For the construction of the models we make two
      major assumptions, justified by electrophysiological observations: i), in the
      closed state, the topology of the inner pore of HCN channels is similar to that
      of K(+) channels. In particular, the orientation of the S5 and S6 helices of HCN
      channels is very similar to that of the corresponding helices of the K(+) KcsA
      and K(+) KirBac1.1 channels. Thus, we use as templates the x-ray structure of
      these K(+) channels. ii), In the open state, the S6 helix is bent further than it
      is in the closed state, as suggested (but not proven) by experimental data. For
      this reason, the template of the open conformation is the x-ray structure of the
      MthK channel. The structural models of the closed state turn out to be consistent
      with all the available electrophysiological data. The model of the open state
      turned out to be consistent with all the available electrophysiological data in
      the filter region, including additional experimental data performed in this work.
      However, it required the introduction of an appropriate, experimentally derived
      constraint for the S6 helix. Our modeling provides a structural framework for
      understanding several functional properties of HCN channels: i), the cysteine
      ring at the inner mouth of the pore may act as a sensor of the intracellular
      oxidizing/reducing conditions; ii), the bending amplitude of the S6 helix upon
      gating appears to be significantly smaller than that found in MthK channels;
      iii), the reduced ionic selectivity of HCN channels, relative to that of K(+)
      channels, may be caused, at least in part, by the larger flexibility of the inner
      pore of HCN channels.

PMID- 15951377
TI  - Effect of salicylate on the elasticity, bending stiffness, and strength of SOPC
      membranes.
AB  - Salicylate is a small amphiphilic molecule which has diverse effects on membranes
      and membrane-mediated processes. We have utilized micropipette aspiration of
      giant unilamellar vesicles to determine salicylate's effects on lecithin membrane
      elasticity, bending rigidity, and strength. Salicylate effectively reduces the
      apparent area compressibility modulus and bending modulus of membranes in a dose
      dependent manner at concentrations above 1 mM, but does not greatly alter the
      actual elastic compressibility modulus at the maximal tested concentration of 10
      mM. The effect of salicylate on membrane strength was investigated using dynamic
      tension spectroscopy, which revealed that salicylate increases the frequency of
      spontaneous defect formation and lowers the energy barrier for unstable hole
      formation. The mechanical and dynamic tension experiments are consistent and
      support a picture in which salicylate disrupts membrane stability by decreasing
      membrane stiffness and membrane thickness. The tension-dependent partitioning of
      salicylate was utilized to calculate the molecular volume of salicylate in the
      membrane. The free energy of transfer for salicylate insertion into the membrane
      and the corresponding partition coefficient were also estimated, and indicated
      favorable salicylate-membrane interactions. The mechanical changes induced by
      salicylate may affect several biological processes, especially those associated
      with membrane curvature and permeability.

PMID- 15951378
TI  - Slowed N-type calcium channel (CaV2.2) deactivation by the cyclin-dependent
      kinase inhibitor roscovitine.
AB  - The lack of a calcium channel agonist (e.g., BayK8644) for CaV2 channels has
      impeded their investigation. Roscovitine, a potent inhibitor of cyclin-dependent
      kinases 1, 2, and 5, has recently been reported to slow the deactivation of P/Q
      type calcium channels (CaV2.1). We show that roscovitine also slows deactivation
      (EC(50) approximately 53 microM) of N-type calcium channels (CaV2.2) and
      investigate gating alterations induced by roscovitine. The onset of slowed
      deactivation was rapid ( approximately 2 s), which contrasts with a slower effect
      of roscovitine to inhibit N-current (EC(50) approximately 300 microM). Slow
      deactivation was specific to roscovitine, since it could not be induced by a
      closely related cyclin-dependent kinase inhibitor, olomoucine (300 microM).
      Intracellularly applied roscovitine failed to slow deactivation, which implies an
      extracellular binding site. The roscovitine-induced slow deactivation was
      accompanied by a slight left shift in the activation-voltage relationship, slower
      activation at negative potentials, and increased inactivation. Additional data
      showed that roscovitine preferentially binds to the open channel to slow
      deactivation. A model where roscovitine reduced a backward rate constant between
      two open states was able to reproduce the effect of roscovitine on both
      activation and deactivation.

PMID- 15951379
TI  - Sterol structure determines miscibility versus melting transitions in lipid
      vesicles.
AB  - Lipid bilayer membranes composed of DOPC, DPPC, and a series of sterols demix
      into coexisting liquid phases below a miscibility transition temperature. We use
      fluorescence microscopy to directly observe phase transitions in vesicles of
      1:1:1 DOPC/DPPC/sterol within giant unilamellar vesicles. We show that vesicles
      containing the "promoter" sterols cholesterol, ergosterol, 25-hydroxycholesterol,
      epicholesterol, or dihydrocholesterol demix into coexisting liquid phases as
      temperature is lowered through the miscibility transition. In contrast, vesicles
      containing the "inhibitor" sterols androstenolone, coprostanol, cholestenone, or
      cholestane form coexisting gel (solid) and liquid phases. Vesicles containing
      lanosterol, a sterol found in the cholesterol and ergosterol synthesis pathways,
      do not exhibit coexisting phases over a wide range of temperatures and
      compositions. Although more detailed phase diagrams and precise distinctions
      between gel and liquid phases are required to fully define the phase behavior of
      these sterols in vesicles, we find that our classifications of promoter and
      inhibitor sterols are consistent with previous designations based on fluorescence
      quenching and detergent resistance. We find no trend in the liquid-liquid or gel
      liquid transition temperatures of membranes with promoter or inhibitor sterols
      and measure the surface fraction of coexisting phases. We find that the vesicle
      phase behavior is related to the structure of the sterols. Promoter sterols have
      flat, fused rings, a hydroxyl headgroup, an alkyl tail, and a small molecular
      area, which are all attributes of "membrane active" sterols.

PMID- 15951380
TI  - Hydroxide and proton migration in aquaporins.
AB  - Hypothetical hydroxide and proton migration along the linear water chain in
      Aquaporin GlpF from Escherichia coli are studied by ab initio Car-Parrinello
      molecular dynamics simulations. It is found that the protein stabilizes a bipolar
      single file of water. The single file features a contiguous set of water-water
      hydrogen bonds in which polarization of the water molecules vary with position
      along the channel axis. Deprotonation of the water chain promotes the
      reorientation of water molecules while the hydroxide ion rapidly migrates by
      sequentially accepting protons from the neighboring water molecules. The
      hydroxide ion is not attracted by a conserved, channel-lining arginine residue,
      but is immobilized at two centrally located, conserved Asparagine-Proline-Alanine
      motifs where fourfold coordination stabilizes the ion. Hydroxide transition from
      the channel vestibules into the channel lumen is strongly influenced by
      electrostatic coupling to two conserved oppositely aligned macrodipoles. This
      suggests that the macrodipole's negative poles play a role in preventing
      hydroxide ions from entering into the channel's inner vestibules. Water
      protonation within the lumen facilitates water reorientation and subsequent
      proton expelling occurs. In the periplasmic half-channel, expelling occurs via
      the Grotthuss mechanism. Protonation within the cytoplasmic half-channel implies
      wire-breakage at the Asn-Pro-Ala motifs. The proton is here diffusively rejected
      as (H(5)O(2))(+).

PMID- 15951381
TI  - Correlated motions in the U1 snRNA stem/loop 2:U1A RBD1 complex.
AB  - The complex formed by U1A RBD1 and the U1 snRNA stem/loop II is noted for its
      high affinity and exquisite specificity. Here, that complex is investigated by 5
      ns molecular dynamics simulations and analyzed by reorientational eigenmode
      dynamics to determine the dynamic properties of the RNA:protein interface that
      could contribute to the binding mechanism. The analysis shows that there is
      extensive correlation between motions of the RNA and protein, involving 7 of the
      10 RNA loop nucleotides, the protein beta-sheet surface, two of its loops, and
      its C-terminal tripeptide sequence. Order parameters of these regions of the
      complex are uniformly high, indicating restricted motion. However, several
      regions of both RNA and protein retain local flexibility, notably three
      nucleotides of the RNA loop and one loop of RBD1 that does not contact RNA. The
      highly correlated motions involving both molecules reflect the intricate network
      of interactions that characterize this complex and could account in part for the
      thermodynamic coupling observed for complex formation.

PMID- 15951382
TI  - Effects of organelle shape on fluorescence recovery after photobleaching.
AB  - The determination of diffusion coefficients from fluorescence recovery data is
      often complicated by geometric constraints imposed by the complex shapes of
      intracellular compartments. To address this issue, diffusion of proteins in the
      lumen of the endoplasmic reticulum (ER) is studied using cell biological and
      computational methods. Fluorescence recovery after photobleaching (FRAP)
      experiments are performed in tissue culture cells expressing GFP-KDEL, a soluble,
      fluorescent protein, in the ER lumen. The three-dimensional (3D) shape of the ER
      is determined by confocal microscopy and computationally reconstructed. Within
      these ER geometries diffusion of solutes is simulated using the method of
      particle strength exchange. The simulations are compared to experimental FRAP
      curves of GFP-KDEL in the same ER region. Comparisons of simulations in the 3D ER
      shapes to simulations in open 3D space show that the constraints imposed by the
      spatial confinement result in two- to fourfold underestimation of the molecular
      diffusion constant in the ER if the geometry is not taken into account. Using the
      same molecular diffusion constant in different simulations, the observed speed of
      fluorescence recovery varies by a factor of 2.5, depending on the particular ER
      geometry and the location of the bleached area. Organelle shape considerably
      influences diffusive transport and must be taken into account when relating
      experimental photobleaching data to molecular diffusion coefficients. This novel
      methodology combines experimental FRAP curves with high accuracy computer
      simulations of diffusion in the same ER geometry to determine the molecular
      diffusion constant of the solute in the particular ER lumen.

PMID- 15951383
TI  - The role of aspartic acid 143 in E. coli tRNA-guanine transglycosylase: insights
      from mutagenesis studies and computational modeling.
AB  - tRNA guanine transglycosylase (TGT) is a tRNA-modifying enzyme which catalyzes
      the posttranscriptional exchange of guanine in position 34 of tRNA(Y,H,N,D) with
      the modified base queuine in eukaryotes or its precursor, preQ(1) base, in
      eubacteria. Thus, TGT must recognize the guanine in tRNA and the free base
      queuine or preQ(1) to catalyze this exchange. The crystal structure of Zymomonas
      mobilis TGT with preQ(1) bound suggests that a key aspartate is critically
      involved in substrate recognition. To explore this, a series of site-directed
      mutants of D143 in Escherichia coli TGT were made and characterized to
      investigate heterocyclic substrate recognition. Our data confirm that D143 has
      significant impact on K(M) of guanine; however, the trend in the K(M) data (D143A
      < D143N < D143S < D143T) is unexpected. Computational studies were used to
      further elucidate the interactions between guanine and the D143 mutants. A
      homology model of E. coli TGT was created, and the role of D143 was investigated
      by molecular dynamic simulations of guanine bound to the wild-type and D143
      mutant TGTs. To validate the model systems against our kinetic data, free
      energies of binding were fit using the linear interaction energy (LIE) method.
      This is a unique application of the LIE method because the same ligand is bound
      to several mutant proteins rather than one protein binding several ligands. The
      atomic detail gained from the simulations provided a better understanding of the
      binding affinities of guanine with the mutant TGTs, revealing that water
      molecules enter the active site and hydrogen bond to the ligand and compensate
      for lost protein-ligand interactions. The trend of binding affinity for wild-type
      > D143A > D143N > D143S > D143T appears to be directly related to the degree of
      hydrogen bonding available to guanine in the binding site.

PMID- 15951384
TI  - Theoretical calculations on hydrogenase kinetics: explanation of the lag phase
      and the enzyme concentration dependence of the activity of hydrogenase uptake.
AB  - Two models of the hydrogenase reaction cycle were investigated by means of
      theoretical calculations and model simulations. The first model is the widely
      accepted triangular hydrogenase reaction cycle with minor modifications; the
      second is a modified triangular model, where we have introduced an autocatalytic
      step into the reaction cycle. Both models include a one-step activation reaction.
      The theoretical calculations and model simulations corroborate the assumed
      autocatalytic reaction step concluded from the experimental characteristics of
      the hydrogenase reaction.

PMID- 15951385
TI  - An autocatalytic step in the reaction cycle of hydrogenase from Thiocapsa
      roseopersicina can explain the special characteristics of the enzyme reaction.
AB  - A moving front has been observed as a special pattern during the hydrogenase
      catalyzed reaction of hydrogen uptake with benzyl viologen as electron acceptor
      in a thin-layer reaction chamber. Such fronts start spontaneously and at random
      times at different points of the reaction chamber; blue spheres are seen
      expanding at constant speed and amplitude. The number of observable starting
      points depends on the hydrogenase concentration. Fronts can be initiated by
      injecting either a small amount of completed reaction mixture or activated
      hydrogenase, but not by injecting a low concentration of reduced benzyl viologen.
      These characteristics are consistent with an autocatalytic reaction step in the
      enzyme reaction. The special characteristics of the hydrogen-uptake reaction in
      the bulk reaction (a long lag phase, and the enzyme concentration dependence of
      the lag phase) support the autocatalytic nature. We conclude that there is at
      least one autocatalytic reaction step in the hydrogenase-catalyzed reaction. The
      two possible autocatalytic schemes for hydrogenase are prion-type autocatalysis,
      in which two enzyme forms interact, and product-activation autocatalysis, where a
      reduced electron acceptor and an inactive enzyme form interact. The experimental
      results strongly support the occurrence of prion-type autocatalysis.

PMID- 15951386
TI  - Exploring global motions and correlations in the ribosome.
AB  - We studied slower global coupled motions of the ribosome with half a microsecond
      of coarse-grained molecular dynamics. A low-resolution anharmonic network model
      that allows for the evolution of tertiary structure and long-scale sampling was
      developed and parameterized. Most importantly, we find that functionally
      important movements of L7/L12 and L1 lateral stalks are anticorrelated. Other
      principal directions of motions include widening of the tRNA cleft and the
      rotation of the small subunit which occurs as one block and is in phase with the
      movement of L1 stalk. The effect of the dynamical correlation pattern on the
      elongation process is discussed. Small fluctuations of the 3' tRNA termini and
      anticodon nucleotides show tight alignment of substrates for the reaction. Our
      model provides an efficient and reliable way to study the dynamics of large
      biomolecular systems composed of both proteins and nucleic acids.

PMID- 15951387
TI  - Mechanochemical model of microtubule structure and self-assembly kinetics.
AB  - Microtubule self-assembly is largely governed by the chemical kinetics and
      thermodynamics of tubulin-tubulin interactions. An important aspect of
      microtubule assembly is that hydrolysis of the beta-tubulin-associated GTP
      promotes protofilament curling. Protofilament curling presumably drives the
      transition from tip structures associated with growth (sheetlike projections and
      blunt ends) to those associated with shortening (rams' horns and frayed ends),
      and transitions between these structures have been proposed to be important for
      growth-shortening transitions. However, previous models for microtubule dynamic
      instability have not considered such structures or mechanics explicitly. Here we
      present a three-dimensional model that explicitly incorporates mechanical stress
      and strain within the microtubule lattice. First, we found that the model
      recapitulates three-dimensional tip structures and rates of assembly and
      disassembly for microtubules grown under standard conditions, and we propose that
      taxol may stabilize microtubule growth by reducing flexural rigidity. Second, in
      contrast to recent suggestions, it was determined that sheetlike tips are more
      likely to undergo catastrophe than blunt tips. Third, partial uncapping of the
      tubulin-GTP cap provides a possible mechanism for microtubule pause events.
      Finally, simulations of the binding and structural effects of XMAP215 produced
      the experimentally observed growth and shortening rates, and tip structure.

PMID- 15951388
TI  - Permeation of aromatic carboxylic acids across lipid bilayers: the pH-partition
      hypothesis revisited.
AB  - According to the pH-partition hypothesis the charged species of organic compounds
      do not contribute to lipid bilayer permeation as they generally show negligible
      partitioning into n-octanol. With this assumption, membrane permeation is related
      to the molar fraction of the neutral species at a particular pH. A recently
      developed permeation assay permits us to directly determine pH-dependent
      permeation of aromatic carboxylic acids. Tb(3+)-loaded liposomes are incubated
      with aromatic carboxylic acids and upon excitation at the absorption wavelength
      of the acid, permeation kinetics can be measured as an increase in Tb(3+)
      luminescence. The anions of the tested acids permeated egg phosphatidylcholine
      membranes only 12 (2-hydroxynicotinic acid), 66 (salicylic acid), and 155
      (dipicolinic acid) times slower than the net neutral species. The anions,
      therefore, controlled the total permeation already at 1-2 pH units above their
      pK(a). These results indicate that in contrast to the expectations of the pH
      partition hypothesis, lipid bilayer permeation of an acidic compound can be
      completely controlled by the anion at physiological pH.

PMID- 15951389
TI  - Theoretical studies of the M2 transmembrane segment of the glycine receptor:
      models of the open pore structure and current-voltage characteristics.
AB  - The pentameric glycine receptor (GlyR), a member of the nicotinicoid superfamily
      of ligand-gated ion channels, is an inhibitory Cl(-) channel that is gated by
      glycine. Using recently published NMR data of the second transmembrane segment
      (M2) of the human alpha1 GlyR, structural models of pentameric assemblies
      embedded in a lipid bilayer were constructed using a combination of
      experimentally determined constraints coupled with all-atom energy minimization.
      Based on this structure of the pentameric M2 "pore", Brownian dynamics
      simulations of ion permeation through this putative conducting open state of the
      channel were carried out. Simulated I-V curves were in good agreement with
      published experimental current-voltage curves and the anion/cation permeability
      ratio, suggesting that our open-state model may be representative of the
      conducting channel of the full-length receptor. These studies also predicted
      regions of chloride occupancy and suggested residues critical to anion
      permeation. Calculations of the conductance of the cation-selective mutant A251E
      channel are also consistent with experimental data. In addition, both rotation
      and untilting of the pore helices of our model were found to be broadly
      consistent with closing of the channel, albeit at distinct regions that may
      reflect alternate gates of the receptor.

PMID- 15951390
TI  - Structural rearrangements in the active site of smooth-muscle myosin.
AB  - Structural rearrangements of the myosin upper-50 kD subdomain are thought to play
      a key role in coordinating actin binding with nucleotide hydrolysis during the
      myosin ATPase cycle. Such rearrangements could open and close the active site in
      opposition to the actin-binding cleft, helping explain the opposing affinities of
      myosin for actin and nucleotide. To directly examine conformational changes
      across the active site during the ATPase cycle we have genetically engineered a
      mutant of chicken smooth-muscle myosin, F344W motor domain essential light chain,
      which contains a single tryptophan (344W) located on a short loop between two
      alpha helixes that traverse the upper-50 kD subdomain in front of the active
      site. Fluorescence resonance energy transfer was examined between the 344W donor
      probe and 2'(3')-O-(N-methylanthraniloyl) (mant)-nucleotide acceptor probes in
      the active site of this construct. The observed fluorescence resonance energy
      transfer efficiencies were 6.4% in the presence of mant ADP and 23.8% in the
      presence of mant ATP, corresponding to distances of 33.4 A and 24.9 A,
      respectively. Our results are consistent with structural rearrangements in which
      there is an 8.5-A closure between the 344W residue and the mant moiety during the
      transition from the strongly (ADP) to weakly (ATP) actin-bound states of the
      myosin ATPase cycle.

PMID- 15951391
TI  - The two-pathway model for the catch-slip transition in biological adhesion.
AB  - Some recently studied biological noncovalent bonds have shown increased lifetime
      when stretched by mechanical force. In each case these counterintuitive "catch
      bonds" have transitioned into ordinary "slip-bonds" that become increasingly
      shorter lived as the tensile force on the bond is further increased. We describe
      analytically how these results are supported by a physical model whereby the
      ligand escapes the receptor binding site via two alternative routes, a catch
      pathway that is opposed by the applied force and a slip-pathway that is promoted
      by force. The model predicts under what conditions and at what critical force the
      catch-to-slip transition would be observed, as well as the degree to which the
      bond lifetime is enhanced at the critical force. The model is applied to four
      experimentally studied systems taken from the literature, involving the binding
      of P- and L-selectins to sialyl Lewis(X) oligosaccharide-containing ligands. Good
      quantitative fit to the experimental data is obtained, both for experiments with
      a constant force and for experiments where the force increases linearly with
      time.

PMID- 15951392
TI  - Dynamics of forward and reverse transport by the glial glycine transporter,
      glyt1b.
AB  - Glycine is a coagonist at the N-methyl-D-aspartate receptor. Changes in
      extracellular glycine concentration may modulate N-methyl-D-aspartate receptor
      function and excitatory synaptic transmission. The GLYT1 glycine transporter is
      present in glia surrounding excitatory synapses, and plays a key role in
      regulating extracellular glycine concentration. We investigated the kinetic and
      other biophysical properties of GLYT1b, stably expressed in CHO cells, using
      whole-cell patch-clamp techniques. Application of glycine produced an inward
      current, which decayed within a few seconds to a steady-state level. When glycine
      was removed, a transient outward current was observed, consistent with reverse
      transport of accumulated glycine. The outward current was enhanced by elevating
      intracellular or lowering extracellular [Na(+)], and was modulated by changes in
      extracellular [glycine] and time of glycine application. We developed a model of
      GLYT1b function, which accurately describes the time course of the transporter
      current under a range of experimental conditions. The model predicts that glial
      uptake of glycine will decay toward zero during a sustained period of elevated
      glycine concentration. This property of GLYT1b may permit spillover from
      glycinergic terminals to nearby excitatory terminals during a prolonged burst of
      inhibitory activity, and reverse transport may extend the period of elevated
      glycine concentration beyond the end of the inhibitory burst.

PMID- 15951393
TI  - Favourable long term prognosis in stable angina pectoris: an extended follow up
      of the angina prognosis study in Stockholm (APSIS).
AB  - OBJECTIVE: To evaluate the long term prognosis of patients with stable angina
      pectoris. DESIGN: Registry based follow up (median 9.1 years) of patients
      participating in the APSIS (angina prognosis study in Stockholm), which was a
      double blind, single centre trial of antianginal drug treatment. PATIENTS: 809
      patients (31% women) with stable angina pectoris < 70 (mean (SD) 59 (7) years at
      inclusion) and an age and sex matched reference population from the same
      catchment area. INTERVENTIONS: Double blind treatment with metoprolol or
      verapamil during 3.4 years (median), followed by referral for usual care with
      open treatment. MAIN OUTCOME MEASURES: Cardiovascular (CV) death and non-fatal
      myocardial infarction (MI) in the APSIS cohort and total mortality in comparison
      with reference subjects. RESULTS: 123 patients died (41 MI, 36 other CV causes)
      and 72 had non-fatal MI. Mortality (19% v 6%, p < 0.001) and fatal MI (6.6% v
      1.6%, p < 0.001) were increased among male compared with female patients.
      Diabetes, previous MI, hypertension, and male sex independently predicted CV
      mortality (p < 0.001). Diabetes greatly increased the risk in a small subgroup of
      female patients. Male patients had higher mortality than men in the reference
      population during the first three years (cumulative absolute difference 3.8%) but
      apparently not thereafter. Female patients had similar mortality to women in the
      reference population throughout the 9.1 years of observation. CONCLUSIONS: Female
      patients with stable angina had similar mortality to matched female reference
      subjects but male patients had an increased risk. Diabetes, previous MI,
      hypertension, and male sex were strong risk factors for CV death or MI.

PMID- 15951394
TI  - Effect of a community heart failure clinic on uptake of beta blockers by patients
      with obstructive airways disease and heart failure.
AB  - OBJECTIVE: To determine the pattern of beta blocker prescribing over one year in
      a heart failure clinic with a structured approach towards initiation and dose
      titration and to give a real life perspective on beta blocker use, compliance,
      and target dose achievement. METHODS: Data were retrospectively analysed on 513
      consecutive patients regularly attending a community heart failure clinic over a
      year. Systolic dysfunction was determined from two dimensional echocardiography
      (left ventricular ejection fraction < or = 40%) and lung function was assessed by
      spirometry. All patients were considered for beta blocker initiation and dose up
      titration. RESULTS: Within one year 157 patients died. 143 patients started beta
      blockers resulting in 315 (88%) patients taking beta blockers at one year; 38%
      were taking the target dose. 124 had evidence of airways obstruction at baseline,
      100 (81%) of whom were taking beta blockers at one year. Forced expiratory volume
      in one second (1.1 v 1.5 l, p < 0.01) and forced vital capacity (2.3 v 2.5 l/min,
      p = 0.2) were not reduced in patients with airways obstruction who received beta
      blockers. Daily doses of beta blockers at one year did not differ statistically
      between patients with obstructive and patients with non-obstructive spirometry
      results. 12 patients discontinued beta blockers and 14 required dose reduction
      due to side effects. CONCLUSION: The majority of patients with heart failure and
      obstructive airways disease can safely tolerate low dose initiation and gradual
      up titration of beta blockers.

PMID- 15951395
TI  - Mitral valve repair for active culture positive infective endocarditis.
AB  - OBJECTIVE: To describe the clinical and echocardiographic outcome after mitral
      valve (MV) repair for active culture positive infective MV endocarditis. PATIENTS
      AND METHODS: Between 1996 and 2004, 36 patients (mean (SD) age 53 (18) years)
      with positive blood culture up to three weeks before surgery (or positive culture
      of material removed at operation) and intraoperative evidence of endocarditis
      underwent MV repair. Staphylococci and streptococci were the most common
      pathogens. All patients had moderate or severe mitral regurgitation (MR). Mean
      New York Heart Association (NYHA) class was 2.3 (1.0). Follow up was complete
      (mean 38 (19) months). RESULTS: Operative mortality was 2.8% (one patient). At
      follow up, endocarditis has not recurred. One patient developed severe recurrent
      MR and underwent valve replacement and one patient had moderate MR. There were
      two late deaths, both non-cardiac. Kaplan-Meier five year freedom from recurrent
      moderate to severe MR, freedom from repeat operation, and survival were 94 (4)%,
      97 (3)%, and 93 (5)%, respectively. At the most recent review the mean NYHA class
      was 1.17 (0.3) (p < 0.0001). At the latest echocardiographic evaluation, left
      atrial diameters, left ventricular end diastolic diameter, and MV diameter were
      significantly reduced (p < 0.05) compared with preoperative values. CONCLUSIONS:
      MV repair for active culture positive endocarditis is associated with low
      operative mortality and provides satisfactory freedom from recurrent infection,
      freedom from repeat operation, and survival. Hence, every effort should be made
      to repair infected MVs and valves should be replaced only when repair is not
      possible.

PMID- 15951396
TI  - Modulation of N-methyl-D-aspartate receptors by donepezil in rat cortical
      neurons.
AB  - Nicotinic acetylcholine receptors and N-methyl-D-aspartate (NMDA) receptors are
      known to be down-regulated in the brain of patients with Alzheimer's disease. It
      was previously shown that the nootropic drugs nefiracetam and galantamine
      potentiate the activity of both nicotinic and NMDA receptors. We hypothesized
      that donepezil, a nootropic with a potent anticholinesterase activity, might also
      affect the NMDA system. NMDA-induced currents were recorded from rat cortical
      neurons in primary culture using the whole-cell patch-clamp technique at a
      holding potential of -70 mV in Mg2+-free solutions. In multipolar neurons, NMDA
      currents were decreased by bath and U-tube applications of 1 to 10 microM
      donepezil but were increased by 30 to 100 microM donepezil. Donepezil suppression
      occurred in a manner independent of NMDA concentrations ranging from 3 to 1000
      microM. The donepezil suppression of NMDA currents was prevented by inhibition of
      protein kinase C (PKC) but unaffected by protein kinase A (PKA) and G proteins.
      In bipolar neurons, however, NMDA currents were potently augmented by bath and U
      tube applications of 0.01 to 100 microM donepezil. Donepezil potentiation
      occurred at high NMDA concentrations that evoked the saturating responses and in
      a manner independent of NMDA concentrations ranging from 3 to 1000 microM. The
      potentiation of NMDA currents by donepezil was decreased by inhibition of PKC and
      abolished by modulation of G proteins but not by PKA inhibition. It was concluded
      that donepezil at low therapeutic concentrations (0.01-1 microM) potentiated the
      activity of the NMDA system and that this action together with cholinesterase
      inhibition would contribute to the improvement of learning, memory, and cognition
      in patients with Alzheimer's disease.

PMID- 15951397
TI  - Uptake of L-carnitine and its short-chain ester propionyl-L-carnitine in the
      isolated perfused rat liver.
AB  - Hepatic uptake of propionyl-L-carnitine (PLC) and L-carnitine (LC) was assessed
      with the impulse-response technique in the single-pass perfused rat liver. The
      experiments involved a rapid injection (impulse) of a mixture of the radiolabeled
      test compound (PLC or LC) and a reference compound (sucrose) into portal vein
      inflow and collection and radiochemical analysis (response) of the venous
      outflowing perfusate samples. The impulse injection was made in the presence of
      increasing unlabeled background concentrations of PLC (0-50 microM) or LC (50-500
      microM) perfusing the liver. The hepatic uptake was minimal or negligible for LC,
      whereas the hepatic influx clearance was found to be low (0.095 ml/s equivalent
      to 5.7 ml/min) for PLC relative to the perfusate flow rate (30 ml/min). When
      background concentrations of PLC were increased (from 1-50 microM), the influx
      clearance was reduced in a concentration-dependent behavior, indicating partial
      saturation of the entry of compound into hepatocytes. PLC was taken up into
      hepatocytes via a unidirectional transport process with negligible efflux. The
      hepatic uptake of PLC was significantly reduced in the presence of unlabeled LC
      (500 microM), indicating an inhibition of the sinusoidal membrane transport of
      PLC by LC. The study showed the sinusoidal membrane is a permeability barrier to
      the entry of PLC and LC into hepatocytes, and it is the site of a common carrier
      mediated transporter for both compounds.

PMID- 15951398
TI  - Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium
      thiosulfate as assessed at the molecular, cellular, and in vivo levels.
AB  - Cisplatin (CDDP) is a common, highly toxic chemotherapeutic agent. This study
      investigates chemoprotective effects of N-acetylcysteine (NAC) and sodium
      thiosulfate (STS) on in vitro and in vivo CDDP toxicities. For ototoxicity
      studies, CDDP (6 mg/kg) was administered to rats via a retrograde carotid artery
      infusion. Auditory brainstem response thresholds at 4 to 20 kHz were tested
      before and 7 days post-treatment. STS (8 g/m(2) i.v.) was administered at 4, 8,
      or 12 h after CDDP. For nephrotoxicity studies, rats were treated with CDDP
      intraperitoneally (10 mg/kg) before or after NAC (400 mg/kg) or STS (8 g/m(2)),
      and blood urea nitrogen (BUN) and creatinine concentrations were measured after 3
      days. In vitro cytotoxicity and chemoprotection in human tumor cell lines were
      assessed by cell viability and immunoblotting assays. Rats treated with STS 4 h
      after CDDP exhibited no hearing change. The STS 8-h group had less otoprotection,
      whereas 12-h rats had ototoxicity. CDDP induced high BUN and creatinine,
      corresponding to renal tubule toxicities. All NAC-treated animals showed normal
      BUN and reduced creatinine levels compared with CDDP alone and no
      histopathological evidence of nephrotoxicity. Delayed STS treatment was not
      consistently protective against nephrotoxicity. STS administration fully
      protected against the in vitro cytotoxic and apoptotic effects of CDDP if added
      within 2 h of CDDP, but chemoprotection decreased if STS administration was 4 h,
      and was minimal by 6 h, after CDDP. Thus, the chemoprotection route and timing of
      administration can be manipulated to maintain CDDP antitumor efficacy while
      protecting against toxicities.

PMID- 15951399
TI  - Lecozotan (SRA-333): a selective serotonin 1A receptor antagonist that enhances
      the stimulated release of glutamate and acetylcholine in the hippocampus and
      possesses cognitive-enhancing properties.
AB  - Recent data has suggested that the 5-hydroxytryptamine (5-HT)(1A) receptor is
      involved in cognitive processing. A novel 5-HT(1A) receptor antagonist, 4-cyano-N
      {2R-[4-(2,3-dihydrobenzo[1,4]-dioxin-5-yl)-piperazin-1-yl]-propyl}-N-pyridin-2-yl
      benzamide HCl (lecozotan), which has been characterized in multiple in vitro and
      in vivo pharmacological assays as a drug to treat cognitive dysfunction, is
      reported. In vitro binding and intrinsic activity determinations demonstrated
      that lecozotan is a potent and selective 5-HT(1A) receptor antagonist. Using in
      vivo microdialysis, lecozotan (0.3 mg/kg s.c.) antagonized the decrease in
      hippocampal extracellular 5-HT induced by a challenge dose (0.3 mg/kg s.c.) of 8
      hydroxy-2-dipropylaminotetralin (8-OH-DPAT) and had no effects alone at doses 10
      fold higher. Lecozotan significantly potentiated the potassium chloride
      stimulated release of glutamate and acetylcholine in the dentate gyrus of the
      hippocampus. Chronic administration of lecozotan did not induce 5-HT(1A) receptor
      tolerance or desensitization in a behavioral model indicative of 5-HT(1A)
      receptor function. In drug discrimination studies, lecozotan (0.01-1 mg/kg i.m.)
      did not substitute for 8-OH-DPAT and produced a dose-related blockade of the 5
      HT(1A) agonist discriminative stimulus cue. In aged rhesus monkeys, lecozotan
      produced a significant improvement in task performance efficiency at an optimal
      dose (1 mg/kg p.o.). Learning deficits induced by the glutamatergic antagonist MK
      801 [(-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]
      (assessed by perceptually complex and visual spatial discrimination) and by
      specific cholinergic lesions of the hippocampus (assessed by visual spatial
      discrimination) were reversed by lecozotan (2 mg/kg i.m.) in marmosets. The
      heterosynaptic nature of the effects of lecozotan imbues this compound with a
      novel mechanism of action directed at the biochemical pathologies underlying
      cognitive loss in Alzheimer's disease.

PMID- 15951400
TI  - The role of Akt and mitogen-activated protein kinase systems in the protective
      effect of poly(ADP-ribose) polymerase inhibition in Langendorff perfused and in
      isoproterenol-damaged rat hearts.
AB  - Blocking poly(ADP-ribosyl)ation of nuclear proteins protects the heart from
      ischemia-reperfusion injury. In addition, activation of Akt and mitogen-activated
      protein kinase (MAPK) cascades also plays a pivotal role in the survival of
      cardiomyocytes during ischemia-reperfusion; however, the potential interplay
      between these pathways is yet to be elucidated. We therefore tested the
      hypothesis whether poly(ADP-ribose) polymerase (PARP) inhibition can modulate Akt
      and MAPK signaling of ischemic-reperfused rat hearts. A novel PARP inhibitor, L
      2286 [2-[(2-piperidin-1-yletil)thio]quinazolin-4(3H)-one] was administered during
      ischemia-reperfusion in Langendorff perfused rat hearts and in isoproterenol
      induced myocardial infarction. Thereafter, the cardiac energy metabolism,
      oxidative damage, and the phosphorylation state of Akt and MAPK cascades were
      monitored. L-2286 exerted significant protective effect against ischemia
      reperfusion-induced myocardial injury in both experimental models. More
      importantly, L-2286 facilitated the ischemia-reperfusion-induced activation of
      Akt, extracellular signal-regulated kinase, and p38-MAPK in both isolated hearts
      and in vivo cardiac injury. By contrast, isoproterenol-induced rapid c-Jun N
      termainal kinase activation was repressed by L-2286. Here, we provide evidence
      for the first time that PARP inhibition beneficially modulates the cardiac Akt
      and MAPK signaling in ex vivo and in vivo ischemia-reperfusion models. We
      therefore propose that this novel mechanism may contribute to the
      cardioprotective properties of PARP inhibitors.

PMID- 15951401
TI  - Modification of heat shock protein 90 by 4-hydroxynonenal in a rat model of
      chronic alcoholic liver disease.
AB  - Lipid peroxidation during oxidative stress leads to increased concentrations of
      thiol-reactive alpha,beta-unsaturated aldehyde, including 4-hydroxy-2-nonenal (4
      HNE) and 4-oxo-2-nonenal (4-ONE). These aldehydes have a documented ability to
      disrupt protein function following adduct formation with specific residues.
      Therefore, to identify 4-HNE-modified proteins in a model of ethanol-induced
      oxidative stress, a proteomic approach was applied to liver fractions prepared
      from rats fed a combination high-fat/ethanol diet. The results revealed that
      essential 90-kDa heat shock protein (Hsp90) was consistently modified by 4-HNE in
      the alcohol-treated animals. In vitro chaperoning experiments using firefly
      luciferase as a client protein were then performed to assess the functional
      effect of 4-HNE modification on purified recombinant human Hsp90, modified with
      concentrations of this aldehyde ranging from 23 to 450 microM. Modification of
      Hsp90 with 4-ONE also led to significant inhibition of the chaperone. Because 4
      HNE and 4-ONE react selectively with Cys, a thiol-specific mechanism of
      inhibition was suggested by these data. Therefore, thiol sensitivity was
      confirmed following treatment of Hsp90 with the specific thiol modifier N
      ethylmaleimide, which resulted in more than 99% inactivation of the chaperone by
      concentrations as low as 6 microM (1:1 M ratio). Finally, tryptic digest of 4-HNE
      modified Hsp90 followed by liquid chromatography/tandem mass spectrometry peptide
      analysis identified Cys 572 as a site for 4-HNE modification. The results
      presented here thus establish that 4-HNE consistently modifies Hsp90 in a rat
      model of alcohol-induced oxidative stress and that the chaperoning activity of
      this protein is subject to dysregulation through thiol modification.

PMID- 15951402
TI  - Early and sustained inhibition of nuclear factor-kappaB prevents hypertension in
      spontaneously hypertensive rats.
AB  - Compelling evidence has emerged pointing to the interaction of oxidative stress
      and renal interstitial inflammation and their mutual contribution to the
      pathogenesis of hypertension in experimental animals. Renal interstitial
      inflammation in spontaneously hypertensive rats (SHR) is accompanied by and
      largely due to activation of redox-sensitive, proinflammatory nuclear
      transcription factor-kappaB (NF-kappaB). Therefore, the present study was
      designed to test the hypothesis that long-term inhibition of NF-kappaB, beginning
      early in the course of the disease, may attenuate renal interstitial inflammation
      and hypertension in SHR. To this end, we administered the reputed NF-kappaB
      inhibitor pyrrolidine dithiocarbamate (PDTC) (100 mg/kg daily intraperitoneally)
      to SHR from 7 to 25 weeks of age and compared the results with vehicle-treated
      SHR. Vehicle-treated and PDTC-treated Wistar Kyoto (WKY) rats served as controls.
      The untreated SHR exhibited a significant rise in arterial pressure; increased NF
      kappaB activation, elevated intercellular adhesion molecule (ICAM)-1 and in situ
      mRNA macrophage chemoattractant molecule-1 (MCP-1) expressions; and interstitial
      accumulation of lymphocytes, macrophages, and angiotensin-II-positive cells. PDTC
      administration prevented the rise in blood pressure, and normalized renal
      cortical NF-kappaB activity as well as ICAM-1 and MCP-1 expressions. This was
      accompanied by a significant reduction in infiltration of immune cells,
      angiotensin II-expressing cells, and renal tissue malondialdehyde content to
      values that matched those found in the control WKY rats. Results suggest that NF
      kappaB-driven intrarenal inflammatory reactivity play a major role in the
      pathogenesis of hypertension in the SHR.

PMID- 15951404
TI  - Ultrasound contrast agents for brain perfusion imaging and ischemic stroke
      therapy.
AB  - Stroke is one of the major causes of death and disabilities in industrialized
      countries. Ultrasound imaging is a largely wide spread bedside technique that is
      easily accessible and valuable in case of emergency but suffers from the fact
      that the ultrasound wave has to cross the skull for brain imaging. However,
      ultrasound contrast agents and new contrast-specific imaging modalities have
      helped to improve the diagnostic quality of transcranial ultrasonography. This
      review article surveys and discusses the current state of microbubbles technology
      and the use of contrast-enhanced transcranial ultrasound for the assessment of
      brain perfusion. Future aspects and expectations in contrast agent functionality,
      such as targeting and drug or gene delivery, acceleration of thrombolysis, and
      imaging technology, are also discussed.

PMID- 15951403
TI  - Differential effects of the 5-hydroxytryptamine (5-HT)1A receptor inverse
      agonists Rec 27/0224 and Rec 27/0074 on electrophysiological responses to 5-HT1A
      receptor activation in rat dorsal raphe nucleus and hippocampus in vitro.
AB  - The pharmacological properties of cyclohexanecarboxylic acid, {2-[4-(2-bromo-5
      methoxybenzyl)piperazin-1-yl]ethyl}-(2-trifluoromethoxyphenyl)amide (Rec
      27/0224), and cyclohexanecarboxylic acid, (2-methoxy-phenyl)-{2-[4-(2
      methoxyphenyl)-piperazin-1-yl]ethyl}amide (Rec 27/0074), were characterized using
      radioligand displacement and guanosine 5'-O-(3-[35S]thiotriphosphate)
      ([35S]GTPgammaS) binding assays, as well as electrophysiological experiments, in
      rat hippocampal and dorsal raphe nucleus (DRN) slices. Both compounds showed a
      high affinity (Ki, approximately 1 nM) and selectivity (>70-fold) at human 5
      hydroxytryptamine (5-HT)1A receptors versus other 5-HT receptors. In
      [35S]GTPgammaS binding assays on HeLa cells stably expressing human 5-HT1A
      receptors, Rec 27/0224 and Rec 27/0074 inhibited basal [35S]GTPgammaS binding by
      44.8 +/- 1.7% (pEC50 = 8.58) and 25 +/- 2.5% (pEC50 = 8.86), respectively. In
      intracellularly recorded CA1 pyramidal cells, 5-HT1A (hetero)receptor-mediated
      hyperpolarization, elicited by 100 nM 5-carboxamidoytryptamine (5-CT), was
      partially antagonized by Rec 27/0224 (approximately 50%; IC50 = 18.0 nM) and Rec
      27/0074 (74%; IC50 = 0.8 nM). In extracellularly recorded DRN serotonergic
      neurons, Rec 27/0224 and Rec 27/0074 fully antagonized the inhibition of firing
      caused by the activation of 5-HT1A (auto)receptors by 30 nM 5-CT with an IC50 of
      34.9 nM and 16.5 nM, respectively. The antagonism had a slow time course,
      reaching a steady state within 60 min. Both compounds also antagonized the
      citalopram-elicited, endogenous 5-HT-mediated inhibition of cell firing. In
      conclusion, Rec 27/0224 and Rec 27/0074 exhibited inverse agonism in
      [35S]GTPgammaS binding assays and differential antagonistic properties on 5-HT1A
      receptor-mediated responses in the hippocampus but not in the DRN. Whether this
      differential effect is causally related to inverse agonist activity is unclear.
      The qualitatively different nature of the antagonism in the hippocampus versus
      the DRN clearly distinguishes the compounds from neutral antagonists, such as N
      {2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-2-pyridinylcyclo-hexanecarboxamide
      (WAY-100635).

PMID- 15951405
TI  - Isotropic component trace analysis.
AB  - A new method for analyzing diffusion tensor imaging (DTI) of the brain, based on
      a recently introduced algorithm, lambda chart analysis (LCA), is presented. Pre
      treatment of a given DTI data set with LCA, which effectively segregates
      isotropic and anisotropic components, allows for total removal of the anisotropic
      component from the DTI data set. The remaining pure isotropic component can
      therefore be subjected to further analysis similar to that applied in the trace
      histogram method. Deconvolution of the trace function yielded 3 Gaussian
      elements. Remapping of these 3 deconvoluted isotropic elements back onto the 2
      dimensional image plane provided anatomical correlates of each element. The
      algorithm, referred to here as isotropic component trace analysis, can be used as
      a pictorial analytic tool, as well as a numerical analytical tool, for the
      noninvasive assessment of isotropic parenchymal components. The presented method
      provides quantitative indices of certain parenchymal parameters with better
      clarity than currently available methods. A ready-to-use program, EZ-LCA, for
      this powerful method is provided (available at http://coe.bri.niigata-u.ac.jp).

PMID- 15951406
TI  - Clinical and angiographic results of dilatation procedures for symptomatic
      intracranial atherosclerotic disease.
AB  - BACKGROUND AND PURPOSE: The authors determined the technical success and the
      clinical and angiographic results of angioplasty and/or stent placement for
      intracranial atherosclerotic disease (ICAD) at a tertiary-care referral hospital.
      METHODS: Angiographic and clinical outcomes occurring within the 1-month follow
      up interval were recorded. Patients were followed up for a mean period of 20.5 +/
      9.2 months, and a neurovascular imaging study was performed in 18 of the 21
      patients alive after a mean period of 19.7 +/- 9.2 months. Stroke-free survival
      and ipsilateral stroke-prevention rates were estimated using Kaplan Meier
      analyses. RESULTS: Twenty-four patients (mean age = 61.0 +/- 13.5 years; 15 were
      men) underwent 30 procedures for treatment of ICAD. The procedures included
      angioplasty (n = 18) and attempted primary stent placement (n = 14). In 2
      procedures, angioplasty was performed in the same session after unsuccessful
      stent placement. There was immediate stenosis reduction (mean +/- SD) from 84% +/
      17% to 27% +/- 21%. The overall 1-month composite rate of major stroke, death,
      and major bleeding complications was 7% for the 30 procedures. Overall stroke
      free survival at 36 months was estimated as 79% (95% confidence interval, 57%
      91%), and the ipsilateral stroke-prevention rate was estimated to be 87% (95%
      confidence interval, 65%-95%). Among the 15 patients who underwent repeat
      angiography, restenosis requiring second intervention was observed in 1 patient.
      No restenosis could be identified in 3 patients who underwent computed
      tomographic or magnetic resonance angiography. CONCLUSION: This single-center
      study demonstrates the feasibility and effectiveness (for secondary stroke
      prevention) of angioplasty and/or stent placement for treatment of ICAD.

PMID- 15951407
TI  - Quantitation of contrast TCD in patients with and without atrial septal aneurysm.
AB  - BACKGROUND AND PURPOSE: Patients with a combination of atrial septal aneurysm
      (ASA) and patent foramen ovale (PFO) have a substantially higher rate of
      recurrent ischemic events as compared to PFO alone. One possible explanation is a
      greater degree of right-to-left shunting with the combination. METHODS:
      Retrospective study using contrast transcranial Doppler ultrasonography (c-TCD)
      to study the degree of shunting in 46 patients with PFO with either transient
      ischemic attack or cryptogenic ischemic stroke. Eight patients with PFO+ASA
      identified on transesophageal echocardiogram were compared to 38 patients with
      PFO but without ASA. RESULTS: The number of embolic counts was no different with
      or without an ASA. Valsalva maneuver increased number of emboli, especially in
      patients with large PFOs. CONCLUSIONS: Patients with ASA in addition to PFO do
      not appear to have an increased risk of right-to-left shunting as measured by c
      TCD as compared to PFO alone.

PMID- 15951408
TI  - Etiology of perfusion-diffusion magnetic resonance imaging mismatch patterns.
AB  - BACKGROUND AND PURPOSE: Diffusion-and perfusion-weighted magnetic resonance
      imaging (DWI and PWI) are useful tools for the assessment of brain ischemia.
      Discrepancies between the extent of DWI and PWI abnormalities are thought to
      depend pre dominantly on time from symptom onset to magnetic resonance imaging
      (MRI) examination. However, underlying ischemic stroke etiology can also be
      important. A mismatch may indicate the presence of tissue at risk for infarction,
      whereas the relevance of other DWI/PWI patterns is uncertain. The authors
      therefore investigated the etiology of brain ischemia in patients with different
      DWI/PWI patterns. METHODS: Retrospective study of 130 patients with acute brain
      ischemia and detailed stroke workup, including MRI within a week after symptom
      onset (40 +/- 39 hours). Patients were divided into the following groups: mis
      match (PWI > DWI), reverse mismatch (DWI > PWI), and match (<25% difference
      between PWI and DWI). RESULTS: Mismatch occurred in 49% of patients, whereas 22%
      had reverse mis-match and 29% matched lesions. Time from symptom onset to MRI
      examination was similar between the 3 groups. Largeartery atherosclerosis
      increased by almost 4-fold the odds of mismatch (odds ratio: 3.89, 95% confidence
      interval: 1.72-8.78; P < .001), whereas patients with reverse mismatch were
      likely to have cryptogenic stroke. Patients with matched lesions were similarly
      distributed among different stroke subtypes. CONCLUSIONS: Ischemic stroke
      etiology appears to influence the development of specific DWI/PWI patterns.
      Prospective studies are needed to confirm these observations.

PMID- 15951409
TI  - Catheter-based aortography fails to identify aortic atherosclerotic lesions
      detected on transesophageal echocardiography.
AB  - BACKGROUND AND PURPOSE: Transesophageal echocardiography is used to detect the
      aortic arch pathology during diagnostic workup of ischemic stroke events.
      Conventional angiography is increasingly used in diagnosing and treating
      atherosclerotic vascular lesions in patients with ischemic stroke. Although
      catheter-based aortography can be performed with cerebral angiography, there is
      limited information about the utility of aortography in identifying
      atherosclerotic abnormalities of the aortic arch. METHODS: A retrospective chart
      review was performed to identify patients who underwent aortography as part of
      their angio-graphic study and transesophageal echocardiography. Both studies were
      reviewed independently in the absence of knowledge of the results of the other
      study. The findings of these aortograms were correlated with the findings of
      transesophageal echocardiography. RESULTS: A total of 34 patients underwent both
      aortography and echocardiography. Of a total of 34 trans esophageal
      echocardiograms, 29 showed abnormal findings in the aorta (85%) and 5 appeared
      normal (15%). These aortic abnormalities included mild to moderate
      atherosclerosis in 18 cases (52%), moderate to severe atherosclerosis in 4 cases
      (12%), and severe atherosclerosis in 7 cases (21%). None of these abnormalities
      were detected by aortography. No disease was visualized in the origin of the
      supraaortic arteries. CONCLUSIONS: Aortic arch atherosclerosis is common in
      patients with ischemic stroke; however, aortograms acquired during conventional
      angiography fail to identify abnormalities detected on transesophageal
      echocardiogram.

PMID- 15951410
TI  - Improved cerebral vasoreactivity after statin administration in healthy adults.
AB  - BACKGROUND AND PURPOSE: Significant improvements of cerebral vasomotor reactivity
      during statin treatment were found in patients with cerebral small-vessel
      disease. The authors analyzed the cerebrovascular CO(2) reactivity before and
      after statin administration in healthy adults using a case-control study design.
      METHODS: The mean cerebral blood flow velocity (CBFV) of both middle cerebral
      arteries and the vasomotor reserve capacity (VMRC) were measured by repeated and
      simultaneous bilateral transcranial Doppler sonography in 25 healthy adults (7
      men, mean age 28.8 years [95% confidence interval (CI): 25.7; 31.9]) before,
      during (days 1, 3, 7, and 14), and after administration of 40 mg pravastatin for
      14 days as compared to 10 healthy control persons (4 men, mean age 30.6 years
      [95% CI: 22.9; 38.3]). The VMRC was calculated off-line as the percentage change
      of CBFV per 1% increase in end-tidal CO2 by a blinded investigator. RESULTS: In
      the statin group, 5 persons were excluded from further analysis. In the remaining
      20 volunteers, the authors observed a highly significant effect of statin
      administration on VMRC (P = .002). The VMRC was significantly increased after
      statin administration on day 7 as compared to the initial value (3.03 [95% CI:
      2.67; 3.38] vs 2.64 [95% CI: 2.41; 2.86]; P = .04). The effect was most
      pronounced in patients with lower initial VMRC values. In the control group, the
      VMRC did not differ significantly from baseline at different time intervals.
      CONCLUSIONS: The findings indicate an improvement of cerebral vasoreactivity even
      after short-term statin administration in healthy adults. However, this effect
      was related to baseline vasoreactivity.

PMID- 15951411
TI  - Longitudinal functional alterations in asymptomatic women at risk for Alzheimer's
      disease.
AB  - PURPOSE: The authors sought to determine whether known alterations of brain
      function in normal individuals who are at high risk for Alzheimer's disease (AD)
      worsen or stay the same after a significant interval of time. METHODS: The
      authors used functional magnetic resonance imaging (fMRI) to observe cortical
      activation during confrontation naming in 14 women with high AD risk and 10 with
      low risk, based on family history and apolipoprotein-E4 allele status. They
      repeated the identical scan protocol in the same patients after 4 years. RESULTS:
      fMRI activation in high-AD-risk participants was found to be further diverged
      from that of their low-AD-risk counterparts over this period. CONCLUSION: fMRI
      may report on the presence and progression of neuropathology in the ventral
      temporal cortex or in functionally connected regions in presymptomatic AD.

PMID- 15951412
TI  - Diffusion-weighted imaging of cerebral malaria.
AB  - Cerebral malaria occurs in 2% of patients infected by Plasmodium falciparum.
      Magnetic resonance imaging findings of small white matter infarcts due to
      cerebral malaria have been previously reported, however nonspecific. Since
      diffusion-weighted imaging can differentiate acute embolic infarcts from other
      chronic or nonspecific white matter lesions, it may aid diagnosis of this illness
      in patients who travel to endemic areas.

PMID- 15951413
TI  - Aortic dissection presenting as an acute ischemic stroke for thrombolysis.
AB  - Thrombolysis for the treatment of acute ischemic stroke requires careful
      selection of patients. The authors report a case of aortic dissection presenting
      with acute ischemic stroke for which emergent ultrasonographic evaluation was
      helpful in the diagnosis and subsequent treatment. The patient presented with
      acute middle cerebral artery ischemic stroke symptoms and complained of bilateral
      ear and chest pain. Chest x-ray, cardiac enzymes, and transthoracic
      echocardiogram were normal, and she was considered for thrombolytic therapy.
      Carotid ultrasound revealed right common carotid occlusion that led to the
      diagnosis of aortic dissection, confirmed by chest computed tomography. An
      experienced sonographer with skills to perform rapid intra- and extracranial
      examinations may help to change the treatment plan for acute stroke patients.

PMID- 15951414
TI  - Wyburn-Mason syndrome.
AB  - Wyburn-Mason syndrome is an uncommon condition in which arteriovenous
      malformations coexist in the visual brain area, in the retina, and in some cases,
      in the face. As a consequence, it has recently been defined as a brain-retino
      facial angiomatosis. The syndrome results from an embryonary insult in the
      development of the optic nerve path and the related vessels from its origin in
      the mesencephalon all the way to the projection to the retina where it usually
      causes unilateral manifestations. Here the authors present an interesting case of
      this ailment and a review of the literature.

PMID- 15951415
TI  - An unusual presentation of rheumatoid meningitis.
AB  - BACKGROUND: Central nervous system involvement in rheumatoid arthritis can rarely
      occur in the absence of systemic disease. Rheumatoid meningitis has not been
      reported to present as spells of neurologic dysfunction. PATIENT AND METHODS: The
      authors describe a woman with a history of well-controlled rheumatoid arthritis
      who presented with headaches and spells of focal neurological dysfunction. Brain
      magnetic resonance imaging, brain biopsy, and temporal artery biopsy were
      required to make the diagnosis of rheumatoid meningitis with arteritis. RESULTS:
      Neuroimaging revealed abnormal leptomeningeal enhancement. Necrotizing
      granulomatous inflammation was seen on meningeal and brain biopsy. A temporal
      artery biopsy showed evidence of arteritis without giant cells. CONCLUSIONS: The
      possibility of central nervous system involvement by rheumatoid arthritis should
      be considered in patients with a history of rheumatoid arthritis even in the
      absence of systemic symptoms. Making the diagnosis may require meningeal and
      brain biopsy. The condition may be steroid responsive.

PMID- 15951416
TI  - Safety of serial monthly administration of triple-dose gadopentetate dimeglumine
      in multiple sclerosis patients: preliminary results of the BECOME trial.

PMID- 15951417
TI  - Nonviremic transmission of West Nile virus.
AB  - West Nile virus (WNV) is now the predominant circulating arthropod-borne virus in
      the United States with >15,000 human cases and >600 fatalities since 1999.
      Conventionally, mosquitoes become infected when feeding on viremic birds and
      subsequently transmit the virus to susceptible hosts. Here, we demonstrate
      nonviremic transmission of WNV between cofeeding mosquitoes. Donor, Culex pipiens
      quinquefasciatus mosquitoes infected with WNV were fed simultaneously with
      uninfected "recipient" mosquitoes on naive mice. At all times, donor and
      recipient mosquitoes were housed in separate sealed containers, precluding the
      possibility of mixing. Recipients became infected in all five trials, with
      infection rates as high as 5.8% and no detectable viremia in the hosts.
      Remarkably, a 2.3% infection rate was observed when 87 uninfected mosquitoes fed
      adjacent to a single infected mosquito. This phenomenon could potentially enhance
      virus survival, transmission, and dispersion and obviate the requirement for
      viremia. All vertebrates, including immune and insusceptible animals, might
      therefore facilitate mosquito infection. Our findings question the status of dead
      end hosts in the WNV transmission cycle and may partly explain the success with
      which WNV established and rapidly dispersed throughout North America.

PMID- 15951418
TI  - Structural basis for ordered substrate binding and cooperativity in aspartate
      transcarbamoylase.
AB  - X-ray structures of aspartate transcarbamoylase in the absence and presence of
      the first substrate carbamoyl phosphate are reported. These two structures in
      conjunction with in silico docking experiments provide snapshots of critical
      events in the function of the enzyme. The ordered substrate binding, observed
      experimentally, can now be structurally explained by a conformational change
      induced upon the binding of carbamoyl phosphate. This induced fit dramatically
      alters the electrostatics of the active site, creating a binding pocket for
      aspartate. Upon aspartate binding, a further change in electrostatics causes a
      second induced fit, the domain closure. This domain closure acts as a clamp that
      both facilitates catalysis by approximation and also initiates the global
      conformational change that manifests homotropic cooperativity.

PMID- 15951419
TI  - Myocardin-related transcription factor B is required in cardiac neural crest for
      smooth muscle differentiation and cardiovascular development.
AB  - Members of the myocardin-related family of transcription factors play critical
      roles in regulating vascular smooth muscle and cardiac differentiation. To
      examine the function of myocardin-related transcription factor (MRTF)-B, mice
      were generated from ES cells harboring a conditional insertional mutation, or
      gene trap, of the MRTF-B gene. Expression of the MRTF-B mutant allele results in
      a fusion protein consisting of the N terminus of MRTF-B fused to beta
      galactosidase, which is functionally null. Homozygous MRTF-B gene trap mice (MRTF
      B-/-) die between embryonic day (E)17.5 and postnatal day 1 from cardiac outflow
      tract defects. MRTF-B is expressed in the premigratory neural crest, in
      rhombomeres 3 and 5, and in the neural crest-derived mesenchyme surrounding the
      aortic arch arteries. Consistent with the pattern of expression, E10.5 and E11.5
      MRTF-B-/- mutants exhibit deformation of aortic arch arteries 3, 4, and 6 and
      severe attenuation of smooth muscle cell differentiation in the arch arteries and
      the aorticopulmonary septum, despite normal migration and initial patterning of
      cardiac neural crest cells. Remarkably, the observed pathology was rescued and
      viable mice generated by intercrossing MRTF-B mutants with mice expressing Cre
      recombinase under the transcriptional control of the neural crest-restricted Wnt
      1 promoter, which results in restoration of normal MRTF-B expression in the
      neural crest. Taken together, these studies reveal that MRTF-B plays a critical
      role in regulating differentiation of cardiac neural crest cells into smooth
      muscle and demonstrate that neural crest-derived smooth muscle differentiation is
      specifically required for normal cardiovascular morphogenesis.

PMID- 15951420
TI  - STRUBBELIG defines a receptor kinase-mediated signaling pathway regulating organ
      development in Arabidopsis.
AB  - An open question remains as to what coordinates cell behavior during
      organogenesis, permitting organs to reach their appropriate size and shape. The
      Arabidopsis gene STRUBBELIG (SUB) defines a receptor-mediated signaling pathway
      in plants. SUB encodes a putative leucine-rich repeat transmembrane receptor-like
      kinase. The mutant sub phenotype suggests that SUB affects the formation and
      shape of several organs by influencing cell morphogenesis, the orientation of the
      division plane, and cell proliferation. Mutational analysis suggests that the
      kinase domain is important for SUB function. Biochemical assays using bacterially
      expressed fusion proteins indicate that the SUB kinase domain lacks enzymatic
      phosphotransfer activity. Furthermore, transgenes encoding WT and different
      mutant variants of SUB were tested for their ability to rescue the mutant sub
      phenotype. These genetic data also indicate that SUB carries a catalytically
      inactive kinase domain. The SUB receptor-like kinase may therefore signal in an
      atypical fashion.

PMID- 15951421
TI  - Substance P inhibits progesterone conversion to neuroactive metabolites in spinal
      sensory circuit: a potential component of nociception.
AB  - A crucial biochemical reaction in vertebrates is progesterone conversion into
      neuroactive metabolites such as dihydroprogesterone (5alpha-DHP) and
      tetrahydroprogesterone (3alpha,5alpha-THP), which regulate several
      neurobiological processes, including stress, depression, neuroprotection, and
      analgesia. 3alpha,5alpha-THP is a potent stimulator of type A receptors of GABA,
      the main inhibitory neurotransmitter. Here, we show that in the spinal sensory
      circuit progesterone conversion into 5alpha-DHP and 3alpha,5alpha-THP is
      inhibited dose-dependently by substance P (SP), a major mediator of painful
      signals. We developed a triple-labeling approach coupled with multichannel
      confocal microscope analysis, which revealed that, in the spinal cord (SC), SP
      releasing afferents project on sensory neurons expressing simultaneously
      neurokinin 1 receptors (rNK1) and key enzymes catalyzing progesterone metabolism.
      Evidence for a potent inhibitory effect of SP on 5alpha-DHP and 3alpha,5alpha-THP
      formation in the SC was provided by combining pulse-chase experiments using
      [3H]progesterone as precursor, HPLC, recrystallization of [3H]metabolites to
      constant specific activity, and continuous flow detection of radioactive
      steroids. The action of SP on progesterone metabolism was mimicked by the rNK1
      specific agonist [Sar-9,Met(O2)11]-SP. The selective rNK1 antagonist SR140333
      totally reversed the effect of SP on progesterone conversion into 5alpha-DHP and
      3alpha,5alpha-THP. These results provide direct evidence for the occurrence of
      anatomical and functional interactions between the SP-rNK1 system and neuroactive
      steroid-producing cells in the SC. The data suggest that, through the local
      control of 3alpha,5alpha-THP concentration in spinal sensory circuit, the SP-rNK1
      system may indirectly interfere with GABA(A) receptor activity in the modulation
      of nociceptive transmission.

PMID- 15951422
TI  - Gene movement by Helitron transposons contributes to the haplotype variability of
      maize.
AB  - Different maize inbred lines are polymorphic for the presence or absence of genic
      sequences at various allelic chromosomal locations. In the bz genomic region,
      located in 9S, sequences homologous to four different genes from rice and
      Arabidopsis are present in line McC but absent from line B73. It is shown here
      that this apparent intraspecific violation of genetic colinearity arises from the
      movement of genes or gene fragments by Helitrons, a recently discovered class of
      eukaryotic transposons. Two Helitrons, HelA and HelB, account for all of the
      genic differences distinguishing the two bz locus haplotypes. HelA is 5.9 kb long
      and contains sequences for three of the four genes found only in the McC bz
      genomic region. A nearly identical copy of HelA was isolated from a 5S
      chromosomal location in B73. Both the 9S and 5S sites appear to be polymorphic in
      maize, suggesting that these Helitrons have been active recently. Helitrons lack
      the strong predictive terminal features of other transposons, so the definition
      of their ends is greatly facilitated by the identification of their vacant sites
      in Helitron-minus lines. The ends of the 2.7-kb HelB Helitron were discerned from
      a comparison of the McC haplotype sequence with that of yet a third line, Mo17,
      because the HelB vacant site is deleted in B73. Maize Helitrons resemble rice
      Pack-MULEs in their ability to capture genes or gene fragments from several loci
      and move them around the genome, features that confer on them a potential role in
      gene evolution.

PMID- 15951423
TI  - Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and
      regenerate infarcted myocardium, improving cardiac function.
AB  - The purpose of this study was to determine whether the heart in large mammals
      contains cardiac progenitor cells that regulate organ homeostasis and regenerate
      dead myocardium after infarction. We report that the dog heart possesses a
      cardiac stem cell pool characterized by undifferentiated cells that are self
      renewing, clonogenic, and multipotent. These clonogenic cells and early committed
      progeny possess a hepatocyte growth factor (HGF)-c-Met and an insulin-like growth
      factor 1 (IGF-1)-IGF-1 receptor system that can be activated to induce their
      migration, proliferation, and survival. Therefore, myocardial infarction was
      induced in chronically instrumented dogs implanted with sonomicrometric crystals
      in the region of the left ventricular wall supplied by the occluded left anterior
      descending coronary artery. After infarction, HGF and IGF-1 were injected
      intramyocardially to stimulate resident cardiac progenitor cells. This
      intervention led to the formation of myocytes and coronary vessels within the
      infarct. Newly generated myocytes expressed nuclear and cytoplasmic proteins
      specific of cardiomyocytes: MEF2C was detected in the nucleus, whereas alpha
      sarcomeric actin, cardiac myosin heavy chain, troponin I, and alpha-actinin were
      identified in the cytoplasm. Connexin 43 and N-cadherin were also present.
      Myocardial reconstitution resulted in a marked recovery of contractile
      performance of the infarcted heart. In conclusion, the activation of resident
      primitive cells in the damaged dog heart can promote a significant restoration of
      dead tissue, which is paralleled by a progressive improvement in cardiac
      function. These results suggest that strategies capable of activating the growth
      reserve of the myocardium may be important in cardiac repair after ischemic
      injury.

PMID- 15951424
TI  - Effects of threshold choice on biological conclusions reached during analysis of
      gene expression by DNA microarrays.
AB  - Global analysis of gene expression by using DNA microarrays is employed
      increasingly to search for differences in biological properties between normal
      and diseased tissue. In such studies, expression that deviates from defined
      thresholds commonly is used for creating genetic signatures that characterize
      disease vs. normality. Although it is axiomatic that the threshold parameters
      applied to microarray analysis will alter the contents of such genetic
      signatures, the extent to which threshold choice can affect the fundamental
      conclusions made from microarray-based studies has not been elucidated. We used
      GABRIEL (Genetic Analysis By Rules Incorporating Expert Logic), a platform of
      knowledge-based algorithms for the global analysis of gene expression, together
      with conventional statistical approaches, to examine the sensitivity of
      conclusions to threshold choice in recently published microarray-based studies.
      An analysis of the effects of threshold decisions in one of these studies
      [Ramaswamy, S., Ross, K. N., Lander, E. S. & Golub, T. R. (2003) Nat. Genet. 33,
      49-54], which arrived at the important conclusion that the metastatic potential
      of primary tumors is encoded by the bulk of cells in the tumor, is the focus of
      this article. We discovered that support for this conclusion highly depends on
      the threshold used to create gene expression signatures. We also found that
      threshold choice dramatically affected the gene function categories represented
      nonrandomly in signatures. Our results suggest that the robustness of biological
      conclusions made by using microarray analysis should be routinely assessed by
      examining the validity of the conclusions by using a range of threshold
      parameters.

PMID- 15951425
TI  - DNA shuffling as a tool for protein crystallization.
AB  - The success of structural studies performed on an individual target in small
      scale or on many targets in the system-wide scale of structural genomics depends
      critically on three parameters: (i) obtaining an expression system capable of
      producing large quantities of the macromolecule(s) of interest, (ii) purifying
      this material in soluble form, and (iii) obtaining diffraction-quality crystals
      suitable for x-ray analysis. The attrition rate caused by these constraints is
      often quite high. Here, we present a strategy that addresses each of these three
      parameters simultaneously. Using DNA shuffling to introduce functional sequence
      variability into a protein of interest, we screened crude lysate supernatants for
      soluble variants that retain enzymatic activity. Crystallization trials performed
      on three WT and eight shuffled enzymes revealed two variants that crystallized
      readily. One of these was used to determine the high-resolution structure of the
      enzyme by x-ray analysis. The sequence diversity introduced through shuffling
      efficiently samples crystal packing space by modifying the surface properties of
      the enzyme. The approach demonstrated here does not require guidance as to the
      type of mutation necessary for improvements in expression, solubility, or
      crystallization. The method is scaleable and can be applied in situations where a
      single protein is being studied or in high-throughput structural genomics
      programs. Furthermore, it should be readily applied to structural studies of
      soluble proteins, membrane proteins, and macromolecular complexes.

PMID- 15951427
TI  - Melanin photoprotection in the human retinal pigment epithelium and its
      correlation with light-induced cell apoptosis.
AB  - Time-resolved electron paramagnetic resonance (TREPR) spectroscopy was used to
      study melanin free radicals in human retinal pigment epithelium (RPE) cells and
      tyrosine-derived synthetic melanin. TREPR signal traces from RPE cells reveal in
      vivo light-induced melanin free radical photochemistry in more detail than
      previously known. Electron spin polarization reflecting a non-Boltzmann
      population within the energy levels of the spin system is observed in RPE cells
      as the result of the triplet state photoproduction and subsequent disappearance
      of free radicals in the melanin polymer. In a set of RPE cells cultured from
      individual sources, differences in optical absorption, continuous wave EPR
      spectra, and TREPR signals were correlated with apoptosis assays performed by
      flow cytometry. Continuous wave EPR spectra of RPE cells and TREPR of acidified
      synthetic melanin suggest that increased melanin aggregation provides an increase
      in photoprotection in the RPE cells that are relatively less susceptible to blue
      light-induced apoptosis.

PMID- 15951426
TI  - Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids.
AB  - Hepatitis B viruses are pararetroviruses that contain a partially dsDNA genome
      and replicate this DNA through an RNA intermediate (the pregenomic RNA, pgRNA) by
      reverse transcription. Viral assembly begins with the packaging of the pgRNA into
      nucleocapsids (NCs), with subsequent reverse transcription within NCs converting
      the pgRNA into the characteristic dsDNA genome. Only NCs containing this dsDNA
      (the so-called "mature" NCs) are enveloped by the viral envelope proteins and
      secreted as virions; "immature" NCs, i.e., those containing pgRNA or immature
      reverse transcription intermediates, are excluded from virion formation. This
      phenomenon is thought to be caused by the emergence of an intrinsic maturation
      signal only on the mature NCs. To define the maturation signal, we have devised a
      method to separate mature from immature duck hepatitis B virus NCs and have
      compared them to NCs derived from secreted virions. Detailed mass spectrometric
      analyses revealed that the core protein from immature NCs was phosphorylated on
      at least six sites, whereas the core protein from mature NCs and that from
      secreted virions was entirely dephosphorylated. These results, together with the
      known requirement of core phosphorylation for pgRNA packaging and DNA synthesis,
      suggest that the NC undergoes a dynamic change in phosphorylation state to
      fulfill its multiple roles at different stages of viral replication. Although
      phosphorylation of the NCs is required for efficient RNA packaging and DNA
      synthesis by the immature NCs, dephosphorylation of the mature NCs may trigger
      envelopment and secretion.

PMID- 15951428
TI  - Dissociated phenotypes in presenilin transgenic mice define functionally distinct
      gamma-secretases.
AB  - Gamma-secretase depends on presence of presenilins (PS), Nct, Aph-1, and PEN-2
      within a core complex. This endoproteolytic activity cleaves within transmembrane
      domains of amyloid-beta precursor protein (APP) and Notch, and familial
      Alzheimer's disease (FAD) mutations in PS1 or PS2 genes shift APP cleavage from
      production of amyloid-beta (Abeta) 40 peptide to greater production of Abeta42.
      Although studies in PS1/PS2-deficient embryonic cells define overlapping
      activities for these proteins, in vivo complementation of PS1-deficient animals
      described here reveals an unexpected spectrum of activities dictated by PS1 and
      PS2 alleles. Unlike PS1 transgenes, wild-type PS2 transgenes expressed in the
      mouse CNS support little Abeta40 or Abeta42 production, and FAD PS2 alleles
      support robust production of only Abeta42. Although wild-type PS2 transgenes
      failed to rescue Notch-associated skeletal defects in PS1 hypomorphs, a "gained"
      competence in this regard was apparent for FAD alleles of PS2. The range of
      discrete and divergent processing activities in mice reconstituted with different
      PS genes and alleles argues against gamma-secretase being a single enzyme with
      intrinsically relaxed substrate and cleavage site specificities. Instead, our
      studies define functionally distinct gamma-secretase variants. We speculate that
      extrinsic components, in combination with core complexes, may tailor functional
      variants of this enzyme to their preferred substrates.

PMID- 15951429
TI  - Cytoskeletal rearrangements and cell extensions induced by the US3 kinase of an
      alphaherpesvirus are associated with enhanced spread.
AB  - The US3 protein is a viral kinase that is conserved among the Alphaherpesvirinae.
      Here, we show that US3 of the swine alphaherpesvirus pseudorabies virus causes
      dramatic alterations in the cytoskeleton, resulting in the formation of long
      actin- and microtubule-containing cell projections in infected and transfected
      cells. Analysis with a GFP-labeled virus showed that multiple virus particles
      move inside the projections toward the tip. GFP-labeled virus could also be found
      in the cytoplasm of neighboring cells that were in contact with the projections.
      In addition, projection formation could be inhibited by using the actin
      stabilizing drug jasplakinolide and could be induced by using the Rho kinase
      inhibitor Y27632. Analyzing the effect of these drugs on intercellular virus
      spread indicated that the observed US3-induced alterations in the host
      cytoskeleton are associated with enhanced intercellular virus spread, thereby
      suggesting a previously undescribed aspect of alphaherpesvirus spread.

PMID- 15951430
TI  - The pgr1 mutation in the Rieske subunit of the cytochrome b6f complex does not
      affect PGR5-dependent cyclic electron transport around photosystem I.
AB  - Although photosystem I (PSI) cyclic electron transport is essential for plants,
      our knowledge of the route taken by electrons is very limited. To assess whether
      ferredoxin (Fd) donates electrons directly to plastoquinone (PQ) or via a Q-cycle
      in the cytochrome (cyt) b(6)f complex in PSI cyclic electron transport, we
      characterized the activity of PSI cyclic electron transport in an Arabidopsis
      mutant, pgr1 (proton gradient regulation). In pgr1, Q-cycle activity was
      hypersensitive to acidification of the thylakoid lumen because of an amino acid
      alteration in the Rieske subunit of the cyt b(6)f complex, resulting in a
      conditional defect in Q-cycle activity. In vitro assays using ruptured
      chloroplasts did not show any difference in the activity of PGR5-dependent PQ
      reduction by Fd, which functions in PSI cyclic electron transport in vivo. In
      contrast to the pgr5 defect, the pgr1 defect did not show any synergistic effect
      on the quantum yield of photosystem II in crr2-2, a mutant in which NDH (NAD(P)H
      dehydrogenase) activity was impaired. Furthermore, the simultaneous determination
      of the quantum yields of both photosystems indicated that the ratio of linear and
      PSI cyclic electron transport was not significantly affected in pgr1. All the
      results indicated that the pgr1 mutation did not affect PGR5-dependent PQ
      reduction by Fd. The phenotypic differences between pgr1 and pgr5 indicate that
      maintenance of the proper balance of linear and PSI cyclic electron transport is
      essential for preventing over-reduction of the stroma.

PMID- 15951431
TI  - A PEST deletion mutant of ABCA1 shows impaired internalization and defective
      cholesterol efflux from late endosomes.
AB  - ATP-binding cassette transporter A1 (ABCA1) promotes the efflux of cellular
      cholesterol and phospholipids to apoA-I. We described previously a cytoplasmic
      PEST sequence in ABCA1 and showed that deletion of the PEST sequence results in a
      prominent increase in the cell surface concentration of ABCA1. In the current
      study we evaluated the hypothesis that the PEST sequence-deleted ABCA1 might
      display defective internalization and trafficking to the late
      endosomes/lysosomes. As assessed by monensin treatment and cell surface
      biotinylation, the internalization rate of PEST sequence-deleted ABCA1 (ABCA1
      dPEST) was markedly decreased compared with wild-type ABCA1 (ABCA1-wt).
      Immunofluorescence confocal microscopy of ABCA1-wt showed both plasma membrane
      localization and substantial co-localization with LAMP2 in late endosomes. In
      contrast, ABCA1-dPEST showed more prominent plasma membrane localization but
      little co-localization with LAMP2. To assess cholesterol efflux from late
      endosomes, HEK293 cells were transiently co-transfected with scavenger receptor A
      (SR-A) and incubated with [3H]cholesterol/acetyl low density lipoprotein (acLDL).
      Although ABCA1-dPEST showed higher cholesterol efflux than did ABCA1-wt following
      cell surface labeling ([3H]cholesterol/acLDL in the absence of SR-A co
      transfection), it showed impaired cholesterol efflux after late endosomal
      labeling ([3H]cholesterol/acLDL in the presence of SR-A). Thus, deletion of the
      PEST sequence leads to a decrease in the internalization of ABCA1 and decreased
      cholesterol efflux from late endosomal cholesterol pools, providing evidence that
      the internalization and trafficking of ABCA1 is functionally important in
      mediating cholesterol efflux from intracellular cholesterol pools.

PMID- 15951432
TI  - Photoactivation perturbs the membrane-embedded contacts between sensory rhodopsin
      II and its transducer.
AB  - The photoactivation mechanism of the sensory rho-dopsin II (SRII)-HtrII receptor
      transducer complex of Natronomonas pharaonis was investigated by time-resolved
      Fourier transform infrared difference spectroscopy to identify structural changes
      associated with early events in the signal relay mechanism from the receptor to
      the transducer. Several prominent bands in the wild-type SRII-HtrII spectra are
      affected by amino acid substitutions at the receptor Tyr(199) and transducer
      Asn(74) residues, which form a hydrogen bond between the two proteins near the
      middle of the bilayer. Our results indicate disappearance of this hydrogen bond
      in the M and O photointermediates, the likely signaling states of the complex.
      This event represents one of the largest light-induced alterations in the binding
      contacts between the receptor and transducer. The vibrational frequency changes
      suggest that Asn(74) and Tyr(199) form other stronger hydrogen bonds in the M
      state. The light-induced disruption of the Tyr(199)-Asn(74) bond also occurs when
      the Schiff base counterion Asp(75) is replaced with a neutral asparagine. We
      compared the decrease in intensity of difference bands assigned to the Tyr(199)
      Asn(74) pair and to chromophore and protein groups of the receptor at various
      time points during the recovery of the initial state. All difference bands
      exhibit similar decay kinetics indicating that reformation of the Tyr(199)
      Asn(74) hydrogen bond occurs concomitantly with the decay of the M and O
      photointermediates. This work demonstrates that the signal relay from SRII to
      HtrII involves early structural alterations in the deeply membrane-embedded
      domain of the complex and provides a spectroscopic signal useful for correlation
      with the downstream events in signal transduction.

PMID- 15951433
TI  - Resistance to the antimicrobial peptide polymyxin requires myristoylation of
      Escherichia coli and Salmonella typhimurium lipid A.
AB  - Attachment of positively charged, amine-containing residues such as 4-amino-4
      deoxy-l-arabinose (l-Ara4N) and phosphoethanolamine (pEtN) to Escherichia coli
      and Salmonella typhimurium lipid A is required for resistance to the cationic
      antimicrobial peptide, polymyxin. In an attempt to discover additional lipid A
      modifications important for polymyxin resistance, we generated polymyxin
      sensitive mutants of an E. coli pmrA(C) strain, WD101. A subset of polymyxin
      sensitive mutants produced a lipid A that lacked both the 3'-acyloxyacyl-linked
      myristate (C(14)) and l-Ara4N, even though the necessary enzymatic machinery
      required to synthesize l-Ara4N-modified lipid A was present. Inactivation of lpxM
      in both E. coli and S. typhimurium resulted in the loss of l-Ara4N addition, as
      well as, increased sensitivity to polymyxin. However, decoration of the lipid A
      phosphate groups with pEtN residues was not effected in lpxM mutants. In summary,
      we demonstrate that attachment of l-Ara4N to the phosphate groups of lipid A and
      the subsequent resistance to polymyxin is dependent upon the presence of the
      secondary linked myristoyl group.

PMID- 15951434
TI  - Isoform-specific interaction of golgin-160 with the Golgi-associated protein
      PIST.
AB  - Golgin-160 belongs to the golgin family of Golgi-localized proteins, which have
      been implicated in Golgi structure and function. Golgin-160 possesses an N
      terminal non-coiled-coil "head" domain followed by an extensive coiled-coil
      region. Using the N-terminal head domain of golgin-160 as bait in a yeast two
      hybrid screen, the postsynaptic density-95/Discs large/zona occludens-1 (PDZ)
      domain protein interacting specifically with TC10 (PIST) was identified to
      interact with golgin-160. PIST (also known as GOPC, CAL, and FIG) has been
      implicated in the trafficking of a subset of plasma membrane proteins, supporting
      a role of golgin-160 in vesicular trafficking. Golgin-160 and PIST colocalize to
      Golgi membranes and interact in vivo. Glutathione S-transferase binding
      experiments identified an internal region of PIST that includes a coiled-coil
      domain, which interacts directly with golgin-160. Similar binding experiments
      identified a leucine-rich repeat within golgin-160 necessary for interaction with
      PIST. Therefore, our data suggest that golgin-160 may participate in PIST
      dependent trafficking of cargo. Interestingly, we also discovered a widely
      expressed isoform of golgin-160, golgin-160B, which lacks the exon encoding the
      leucine repeat that mediates binding to PIST. As predicted, golgin-160B was
      unable to bind PIST. Full-length golgin-160 and golgin-160B may link distinct
      subsets of proteins to effect specific membrane trafficking pathways.

PMID- 15951435
TI  - Cysteine-mediated cross-linking indicates that subunit C of the V-ATPase is in
      close proximity to subunits E and G of the V1 domain and subunit a of the V0
      domain.
AB  - The vacuolar (H+)-ATPases (V-ATPases) are multisubunit complexes responsible for
      ATP-dependent proton transport across both intracellular and plasma membranes.
      The V-ATPases are composed of a peripheral domain (V1) that hydrolyzes ATP and an
      integral domain (V0) that conducts protons. Dissociation of V1 and V0 is an
      important mechanism of controlling V-ATPase activity in vivo. The crystal
      structure of subunit C of the V-ATPase reveals two globular domains connected by
      a flexible linker (Drory, O., Frolow, F., and Nelson, N. (2004) EMBO Rep. 5, 1
      5). Subunit C is unique in being released from both V1 and V0 upon in vivo
      dissociation. To localize subunit C within the V-ATPase complex, unique cysteine
      residues were introduced into 25 structurally defined sites within the yeast C
      subunit and used as sites of attachment of the photoactivated sulfhydryl reagent
      4-(N-maleimido)benzophenone (MBP). Analysis of photocross-linked products by
      Western blot reveals that subunit E (part of V1) is in close proximity to both
      the head domain (residues 166-263) and foot domain (residues 1-151 and 287-392)
      of subunit C. By contrast, subunit G (also part of V1) shows cross-linking to
      only the head domain whereas subunit a (part of V0) shows cross-linking to only
      the foot domain. The localization of subunit C to the interface of the V1 and V0
      domains is consistent with a role for this subunit in controlling assembly of the
      V-ATPase complex.

PMID- 15951437
TI  - CD2-associated protein (CD2AP) expression in podocytes rescues lethality of CD2AP
      deficiency.
AB  - Mice born without CD2-associated protein (CD2AP) develop renal failure and
      nephrotic syndrome about 4 weeks after birth and die around 6 weeks of age.
      Although CD2AP is widely expressed, the severity of the renal failure precludes a
      clear determination of the role of CD2AP in other tissues. Here we generated
      transgenic mice expressing CD2AP using a podocyte-specific promoter. Podocyte
      specific expression of CD2AP prevented the development of proteinuria,
      demonstrating that the renal failure is solely due to loss of CD2AP in podocytes
      and not in other renal or in immune cells. CD2AP-deficient mice are long-lived
      and appear phenotypically normal. Histological analysis demonstrated testicular
      abnormalities that were age-related. CIN85, a paralog of CD2AP, is poorly
      expressed in both the podocyte and the basal seminiferous tubule, suggesting that
      the loss of CD2AP in specific tissues may be compensated for by CIN85.

PMID- 15951436
TI  - Loss of outer membrane proteins without inhibition of lipid export in an
      Escherichia coli YaeT mutant.
AB  - Escherichia coli yaeT encodes an essential, conserved outer membrane (OM) protein
      that is an ortholog of Neisseria meningitidis Omp85. Conflicting data with N.
      meningitidis indicate that Omp85 functions either in assembly of OM proteins or
      in export of OM lipids. The role of YaeT in E. coli was investigated with a new
      temperature-sensitive mutant harboring nine amino acid substitutions. The mutant
      stops growing after 60 min at 44 degrees C. After 30 min at 44 degrees C,
      incorporation of [35S]methionine into newly synthesized OM proteins is
      selectively inhibited. Synthesis and export of OM phospholipids and
      lipopolysaccharide are not impaired. OM protein levels are low, even at 30
      degrees C, and the buoyant density of the OM is correspondingly lower. By Western
      blotting, we show that levels of the major OM protein OmpA are lower in the
      mutant in whole cells, membranes, and the growth medium. SecA functions as a
      multicopy suppressor of the temperature-sensitive phenotype and partially
      restores OM proteins. Our data are consistent with a critical role for YaeT in OM
      protein assembly in E. coli.

PMID- 15951438
TI  - The evolutionarily related beta-barrel polypeptide transporters from Pisum
      sativum and Nostoc PCC7120 contain two distinct functional domains.
AB  - Several beta-barrel-type channels are involved in the translocation or assembly
      of outer membrane proteins of bacteria or endosymbiotically derived organelles.
      Here we analyzed the functional units of the beta-barrel polypeptide transporter
      Toc75 (translocon in outer envelope of chloroplasts) of the outer envelope of
      chloroplasts and of a protein, alr2269, from Nostoc PCC7120 with homology to
      Toc75, both proteins having a similar domain organization. We demonstrated that
      the N-terminal region functions as a recognition and complex assembly unit,
      whereas the C terminus forms the beta-barrel-type pore. The pore region is, in
      turn, modulated by the N terminus of the proteins. The protein from Nostoc
      PCC7120, which shares a common ancestor with Toc75, is able to recognize
      precursor proteins destined for chloroplasts. In contrast, the recognition of
      peripheral translocon subunits by Toc75 is a novel feature acquired through
      evolution.

PMID- 15951439
TI  - Role of sphingosine kinase 2 in cell migration toward epidermal growth factor.
AB  - Sphingosine 1-phosphate (S1P), produced by two sphingosine kinase isoenzymes,
      denoted SphK1 and SphK2, is the ligand for a family of five specific G protein
      coupled receptors that regulate cytoskeletal rearrangements and cell motility.
      Whereas many growth factors stimulate SphK1, much less is known of the regulation
      of SphK2. Here we report that epidermal growth factor (EGF) stimulated SphK2 in
      HEK 293 cells. This is the first example of an agonist-dependent regulation of
      SphK2. Chemotaxis of HEK 293 cells toward EGF was inhibited by N,N
      dimethylsphingosine, a competitive inhibitor of both SphKs, implicating S1P
      generation in this process. Down-regulating expression of SphK1 in HEK 293 cells
      with a specific siRNA abrogated migration toward EGF, whereas decreasing SphK2
      expression had no effect. EGF contributes to the invasiveness of human breast
      cancer cells, and EGF receptor expression is associated with poor prognosis. EGF
      also stimulated SphK2 in MDA-MB-453 breast cancer cells. Surprisingly, however,
      down-regulation of SphK2 in these cells completely eliminated migration toward
      EGF without affecting fibronectin-induced haptotaxis. Our results suggest that
      SphK2 plays an important role in migration of MDA-MB-453 cells toward EGF.

PMID- 15951440
TI  - Identification of S-hydroxylysyl-methionine as the covalent cross-link of the
      noncollagenous (NC1) hexamer of the alpha1alpha1alpha2 collagen IV network: a
      role for the post-translational modification of lysine 211 to hydroxylysine 211
      in hexamer assembly.
AB  - Collagen IV networks are present in all metazoans as components of basement
      membranes that underlie epithelia. They are assembled by the oligomerization of
      triple-helical protomers, composed of three alpha-chains. The trimeric
      noncollagenous domains (NC1) of each protomer interact forming a hexamer
      structure. Upon exposure to acidic pH or denaturants, the hexamer dissociates
      into monomer and dimer subunits, the latter reflect distinct interactions that
      reinforce/cross-link the quaternary structure of hexamer. Recently, the cross
      link site of the alpha1alpha1alpha2 network was identified, on the basis of x-ray
      crystal structures at 1.9-A resolution, in which the side chains of Met93 and
      Lys211 were proposed to be connected by a novel thioether bond (Than, M. E.,
      Henrich, S., Huber, R., Ries, A., Mann, K., Kuhn, K., Timpl, R., Bourenkov, G.
      P., Bartunik, H. D., and Bode, W. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 6607
      6612); however, at the higher resolution of 1.5 A, we found no evidence for this
      cross-link (Vanacore, R. M., Shanmugasundararaj, S., Friedman, D. B., Bondar, O.,
      Hudson, B. G., and Sundaramoorthy, M. (2004) J. Biol. Chem. 279, 44723-44730).
      Given this discrepancy in crystallographic findings, we sought chemical evidence
      for the location and nature of the reinforcement/cross-link site. Trypsin
      digestion of monomer and dimer subunits excised a approximately 5,000-Da complex
      that distinguished dimers from monomers; the complex was characterized by mass
      spectrometry, Edman degradation, and amino acid composition analyses. The tryptic
      complex, composed of two peptides of 44 residues derived from two alpha1 NC1
      monomers, contained Met93 and Lys211 post-translationally modified to
      hydroxylysine (Hyl211). Truncation of the tryptic complex with post-proline
      endopeptidase reduced its size to 14 residues to facilitate characterization by
      tandem mass spectrometry, which revealed a covalent linkage between Met93 and
      Hyl211. The novel cross-link, termed S-hydroxylysyl-methionine, reflects at least
      two post-translational events in its formation: the hydroxylation of Lys211 to
      Hyl211 within the NC1 domain during the biosynthesis of alpha-chains and the
      connection of Hyl211 to Met93 between the trimeric NC1 domains of two adjoining
      triple-helical protomers, reinforcing the stability of collagen IV networks.

PMID- 15951441
TI  - NIBP, a novel NIK and IKK(beta)-binding protein that enhances NF-(kappa)B
      activation.
AB  - The transcription factor NF-kappaB plays an important role in both physiological
      and pathological events in the central nervous system. Nevertheless, the
      mechanisms of NF-kappaB-mediated regulation of gene expression, and the signaling
      molecules participating in the NF-kappaB pathway in the central nervous system
      are, to date, poorly understood. To identify such molecules, we conducted a yeast
      two-hybrid screen of a human brain cDNA library using NIK as bait. As a result,
      we identified a novel NIK and IKK(beta) binding protein designated NIBP that is
      mainly expressed in brain, muscle, heart, and kidney. Interestingly, low levels
      of expression were detected in immune tissues such as spleen, thymus, and
      peripheral blood leukocytes, where NF-kappaB is known to modulate immune
      function. We demonstrated by immunohistochemistry that NIBP expression in the
      brain is localized to neurons. NIBP physically interacts with NIK, IKK(beta), but
      not IKK(alpha) or IKK(gamma). NIBP overexpression potentiates tumor necrosis
      factor-alpha-induced NF-kappaB activation through increased phosphorylation of
      the IKK complex and its downstream I(kappa)B(alpha) and p65 substrates. Finally,
      knockdown of NIBP expression by small interfering RNA reduces tumor necrosis
      factor-alpha-induced NF-kappaB activation, prevents nerve growth factor-induced
      neuronal differentiation, and decreases Bcl-xL gene expression in PC12 cells. Our
      data demonstrate that NIBP, by interacting with NIK and IKK(beta), is a new
      enhancer of the cytokine-induced NF-(kappa)B signaling pathway. Because of its
      neuronal expression, we propose that NIBP may be a potential target for
      modulating the NF-(kappa)B signaling cascade in neuronal pathologies dependent
      upon abnormal activation of this pathway.

PMID- 15951443
TI  - Effective translation of the second cistron in two Drosophila dicistronic
      transcripts is determined by the absence of in-frame AUG codons in the first
      cistron.
AB  - The novel dicistronic transcript encoded by the Drosophila melanogaster stoned
      gene was recognized as being unusual in that the protein encoded by the first
      open reading frame, stoned-A (STNA), contains no internal methionine residues in
      a protein of 93 kDa. The dicistronic nature of the stoned locus and the lack of
      methionine residues in STNA is conserved across dipteran species. A second
      methionine-free cistron, encoding Snapin, was identified in Drosophila and also
      found to be dicistronic, the second open reading frame (ORF) encoding a
      methyltransferase. We have replaced the methyltransferase cistron with green
      fluorescent protein (GFP) and used this dicistronic construct to show that the
      GFP cistron is translated in Drosophila S2 cells. The insertion of in-frame AUG
      codons into the snapin ORF attenuates the translation of GFP, and the level of
      attenuation correlates with the number of inserted AUGs. Increasing the
      efficiency of translation-initiation of the Snapin cistron also attenuates the
      translation of GFP. This indicates that failure to initiate translation at the
      first AUG allows ribosomes to scan through the Snapin ORF and to initiate
      translation of the second cistron, unless new AUG codons are inserted. These data
      are used to interpret the expression of the stoned locus and in particular, to
      explain the altered stoned protein levels in the stoned-temperature-sensitive
      mutant allele, which replaces a lysine with a methionine codon early in the
      first, stonedA, cistron.

PMID- 15951442
TI  - Key role of conserved histidines in recombinant mouse beta-carotene 15,15'
      monooxygenase-1 activity.
AB  - Alignment of sequences of vertebrate beta-carotene 15,15'-monooxygenase-1 (BCMO1)
      and related oxygenases revealed four perfectly conserved histidines and five
      acidic residues (His172, His237, His308, His514, Asp52, Glu140, Glu314, Glu405,
      and Glu457 in mouse BCMO1). Because BCMO1 activity is iron-dependent, we propose
      that these residues participate in iron coordination and therefore are essential
      for catalytic activity. To test this hypothesis, we produced mutant forms of
      mouse BCMO1 by replacing the conserved histidines and acidic residues as well as
      four histidines and one glutamate non-conserved in the overall family with
      alanines by site-directed mutagenesis. Our in vitro and in vivo data showed that
      mutation of any of the four conserved histidines and Glu405 caused total loss of
      activity. However, mutations of non-conserved histidines or any of the other
      conserved acidic residues produced impaired although enzymatically active
      proteins, with a decrease in activity mostly due to changes in V(max). The iron
      bound to protein was determined by inductively coupled plasma atomic emission
      spectrometry. Bound iron was much lower in preparations of inactive mutants than
      in the wild-type protein. Therefore, the conserved histidines and Glu405 are
      absolutely required for the catalytic mechanism of BCMO1. Because the mutant
      proteins are impaired in iron binding, these residues are concluded to coordinate
      iron required for catalytic activity. These data are discussed in the context of
      the predicted structure for the related eubacterial apocarotenal oxygenase.

PMID- 15951444
TI  - 3'-Untranslated region of phosphoenolpyruvate carboxykinase mRNA contains
      multiple instability elements that bind AUF1.
AB  - Phosphoenolpyruvate carboxykinase (PEPCK) is regulated solely by alterations in
      gene expression that involve changes in rates of PEPCK mRNA transcription and
      degradation. A tetracycline-responsive promoter system was used to quantify the
      half-life of various chimeric beta-globin-PEPCK (betaG-PCK) mRNAs in LLC-PK -F(+)
      cells. The control betaG mRNA was extremely stable (t(1/2) = 5 days). However,
      betaG-PCK-1 mRNA, which contains the entire 3'-UTR of the PEPCK mRNA, was
      degraded with a half-life of 1.2 h. RNase H treatment indicated that rapid
      deadenylation occurred concomitant with degradation of the betaG-PCK-1 mRNA.
      Previous studies indicate that PCK-7, a 50-nucleotide segment at the 3'-end of
      the 3'-UTR, binds an unidentified protein that may contribute to the rapid decay
      of the PEPCK mRNA. However, the chimeric betaG-PCK-7 mRNA has a half-life of 17
      h. Inclusion of the adjacent PCK-6 segment, a 23-bp AU-rich region, produced the
      betaG-PCK-6/7 mRNA, which has a half-life of 3.6 h. The betaG-PCK-3 mRNA that
      contains the 3'-half of 3'-UTR was degraded with the same half-life.
      Surprisingly, the betaG-PCK-2 mRNA, containing the 5'-end of the 3'-UTR, was also
      degraded rapidly (t((1/2)) = 5.4 h). RNA gel shift analyses established that AUF1
      (hnRNP D) binds to the PCK-7, PCK-6, and PCK-2 segments with high affinity and
      specificity. Mutational analysis indicated that AUF1 binds to a UUAUUUUAU
      sequence within PCK-6 and the stem-loop structure and adjacent CU-region of PCK
      7. Thus, AUF1 binds to multiple destabilizing elements within the 3'-UTR that
      participate in the rapid turnover of the PEPCK mRNA.

PMID- 15951445
TI  - The use of calnexin and calreticulin by cellular and viral glycoproteins.
AB  - Calnexin and calreticulin are homologous lectin chaperones that assist maturation
      of cellular and viral glycoproteins in the mammalian endoplasmic reticulum.
      Calnexin and calreticulin share the same specificity for monoglucosylated protein
      bound N-glycans but associate with a distinct set of newly synthesized
      polypeptides. We report here that most calnexin substrates do not associate with
      calreticulin even upon selective calnexin inactivation, while BiP associates more
      abundantly with nascent polypeptides under these conditions. Calreticulin
      associated more abundantly with orphan calnexin substrates only in infected cells
      and preferentially with polypeptides of viral origin, showing stronger dependence
      of model viral glycoproteins on endoplasmic reticulum lectins. This may explain
      why inactivation of the calnexin cycle affects viral replication and infectivity
      but not viability of mammalian cells.

PMID- 15951446
TI  - Direct determination of unbound intrinsic drug clearance in the microsomal
      stability assay.
AB  - The microsomal stability assay is commonly used to rank compounds according to
      their metabolic stability. Determination of the unbound intrinsic clearance
      (CL(in,u)) is essential for the accurate comparison of compounds, since
      nonspecific binding to microsomes can lead to an underestimation of the
      microsomal clearance. In this study, a new method (linear extrapolation in the
      stability assay, LESA) was established, which allows direct calculation of
      CL(in,u) from microsomal stability data, without the need to independently
      determine the fraction of free (unbound) drug. The method was validated using
      nine drugs with different chemical structures and physicochemical properties. The
      CL(in,u) of these compounds was extrapolated from the intrinsic clearance values
      obtained at different concentrations of human liver microsomes and compared with
      that calculated by the conventional method, using microsomal intrinsic clearance
      values and the free fraction of drug determined by equilibrium dialysis,
      ultracentrifugation, or ultrafiltration. A good agreement was observed between
      the data generated by the LESA method and those determined by conventional
      procedures. The method was further evaluated using a published dataset for 10
      additional drugs and found to yield intrinsic clearance data comparable to the
      previously reported values. LESA provides a convenient and rapid method to
      determine the influence of microsome binding on intrinsic clearance in a single
      assay.

PMID- 15951447
TI  - Quantitative analysis of cytochrome p450 isozymes by means of unique isozyme
      specific tryptic peptides: a proteomic approach.
AB  - A novel matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)
      mass spectrometry method has been developed to quantitate cytochrome P450 (P450)
      isozymes based on their unique isozyme-specific tryptic peptides. It was shown
      that the molar ratio of P450 isozyme-specific peptides is linearly proportional
      to the mass peak area ratio of corresponding peptides not only in simple two
      peptide mixtures, but also in complex digest mixtures. This approach is
      applicable both to in-gel (as shown for CYP2B1 and CYP2B2) and in-solution
      digests (as shown for CYP1A2, CYP2E1, and CYP2C19) and does not require
      introduction of stable isotopes or labeling with isotope-coded affinity tagging.
      The relative and absolute quantitation can be performed after developing
      corresponding calibration curves with synthesized P450 isozyme-specific peptide
      standards. The absolute quantitation of human P450 isozymes was performed by
      using CYP2B2 isozyme-specific peptide (1306.7 Da) as the universal internal
      standard. The utility of this approach was demonstrated for two highly homologous
      (>97%) rat liver CYP2B1 and CYP2B2 and three human P450 isozymes belonging to two
      different families and three different subfamilies: CYP1A2, CYP2E1, and CYP2C19.
      In summary, we have demonstrated that MALDI TOF-based peptide mass fingerprinting
      of different cytochrome P450 isozymes can provide not only qualitative but
      quantitative data, too.

PMID- 15951448
TI  - Sulfonation of environmental chemicals and their metabolites in the polar bear
      (Ursus maritimus).
AB  - Although its habitat comprises mostly remote regions of the Arctic, the polar
      bear is subject to bioaccumulation of persistent environmental pollutants. Along
      with their phase I metabolites, they are potential substrates for detoxification
      via sulfonation and glucuronidation. The capability of polar bear liver to
      sulfonate a structurally diverse group of environmental chemicals, that is, 3
      hydroxybenzo[a]pyrene (3-OH-B[a]P), triclosan, 4'-hydroxy-3,3',4,5'
      tetrachlorobiphenyl (4'OH-PCB79), 4'-hydroxy-2,3,3',4,5,5'-hexachlorobiphenyl (4'
      OH-PCB159), 4'-hydroxy-2,3,3',5,5',6-hexachlorobiphenyl (4'-OH-PCB165), the
      methoxychlor metabolite 2-(4-methoxyphenyl)-2-(4-hydroxyphenyl)-1,1,1
      trichloroethane (OHMXC), tris(4-chlorophenyl)-methanol (TCPM), and
      pentachlorophenol (PCP) was investigated. The glucuronidation of 3-OH-B[a]P was
      also studied. Enzyme activity was assayed by incubation of liver cytosol or
      microsomes derived from three adult male polar bears with 3'-phosphoadenosine-5'
      phosphosulfate or uridine 5'-diphosphoglucuronic acid and substrate, followed by
      fluorometric or radiochemical thin-layer chromatographic analysis. The efficiency
      of sulfonation decreased in the order 3-OH-B[a]P >>> triclosan >> 4'-OH-PCB79 >
      OHMXC > 4'-OH-PCB165 > TCPM > 4'-OH-PCB159 > PCP, all of which produced
      detectable sulfate conjugates. The 3-OH-B[a]P substrate was readily sulfonated
      and glucuronidated (apparent K(m) 0.41, 1.4 microM, and apparent V(max) 0.50,
      3.00 nmol/min/mg, respectively). UDP-glucuronic acid kinetics suggested the
      presence of multiple enzymes glucuronidating 3-OH-B[a]P. Substrate inhibition was
      observed for the sulfonation of 3-OH-B[a]P and 4'OH-PCB79 (K(i) 1.0 and 217
      microM, respectively). Triclosan was the most rapidly sulfated (apparent V(max)
      1008 pmol/min/mg) of the substrates tested. Since sulfonation of an acyclic
      tertiary alcoholic group, as in TCPM, has not previously been reported, we also
      examined TCPM conjugation in humans and catfish, both of which formed TCPM
      sulfate. The hexachlorinated polychlorinated biphenylols, TCPM, and PCP were poor
      substrates for sulfonation, suggesting that this may be one reason why these
      substances and structurally similar xenobiotics persist in polar bears.

PMID- 15951449
TI  - Canalicular and sinusoidal disposition of bilirubin mono- and diglucuronides in
      sandwich-cultured human and rat primary hepatocytes.
AB  - Due to cholestasis or adverse drug effects, the excretion of bilirubin conjugates
      can decrease; therefore, the level of bilirubin (B) and bilirubin glucuronides
      (BGs) increases in the serum with the concomitant shift of bilirubin diversus
      monoglucuronide (BDG/BMG) equilibrium. The aim of this study was to utilize the
      collagen-sandwich culture of hepatocytes as an in vitro model for studying B
      conjugation and canalicular versus sinusoidal disposition of BGs. Canalicular and
      sinusoidal efflux of BMG and BDG obtained in sandwich-cultured rat primary
      hepatocytes was compared with that measured in human hepatocyte cultures. The BMG
      and BDG were separated by high-performance liquid chromatography and identified
      by mass spectrometry. The biliary excretion index (BEI) was estimated by
      measuring disposition of BGs into standard and Ca(2+), Mg(2+)-free medium.
      Significantly more BGs were excreted into the canalicular networks than into the
      medium in 96-h sandwich culture of both human and rat hepatocytes (BEI, 62.5 and
      80.6, respectively). The BDG/BMG ratio in the medium versus that in the
      canalicular networks was 0.55/1.48, which is similar to the serum/bile values
      (0.6/1.5) observed in vivo by Mesa et al. [Mesa VA, De Vos R, and Fevery J (1997)
      J Hepatol 27:912-916]. In contrast, the BEI for p-nitrophenol glucuronide was
      5.2. The low BEI value is in agreement with empirical observations, which suggest
      that molecules with low molecular weight are preferably excreted by the kidney.
      In conclusion, sandwich-cultured primary hepatocytes provide a useful in vitro
      method to differentiate between sinusoidal and canalicular disposition of BGs.
      Since the normal BDG/BMG ratio changes in hyperbilirubinemia, this model could be
      used to predict drug effects leading to hyperbilirubinemia.

PMID- 15951450
TI  - The use of sandwich-cultured rat hepatocytes to determine the intrinsic clearance
      of compounds with different extraction ratios: 7-ethoxycoumarin and warfarin.
AB  - The application of sandwich-cultured rat hepatocytes for the identification of
      the hepatic intrinsic clearance of compounds with widely varying extraction
      ratios was investigated. We previously showed the applicability of this in vitro
      system, in combination with a model describing molecular diffusion,
      hepatocyte/medium partition, and nonsaturated metabolism, which resulted in a
      successful identification of this parameter for tolbutamide. This approach is
      further validated using the compounds 7-ethoxycoumarin and warfarin, covering a
      100-fold range of extraction ratios. Clearance of these two substrates could be
      reliably determined, but only if the depletion of the parent compound in medium
      as well as in the hepatocyte sandwich was measured. Sensitivity analyses showed
      that the time course of depletion of the parent compound in medium, especially
      for warfarin, is insensitive to the partition and diffusion parameter values,
      whereas depletion in the hepatocyte sandwich was far more sensitive. When varying
      the volumes of collagen in the sandwich culture, it appears that the most
      reliable kinetic parameters could be obtained by fitting the data with the
      smaller collagen volume and that these parameters obtained from fitting to data
      of the larger volumes generally cannot be verified satisfactorily with the data
      of the smaller volumes. The values of hepatic clearance that were obtained after
      extrapolation of the intrinsic clearance to the hepatic clearance from blood were
      comparable within a factor of 2 to hepatic clearance data in the literature. This
      indicates that this sandwich culture and modeling system can be applied for the
      identification of the hepatic intrinsic clearance rate of the total range from
      low to high clearance compounds.

PMID- 15951451
TI  - Benefits, harms, and the design of clinical trials.

PMID- 15951452
TI  - Are we ready for patient-based effect sizes in clinical-trials research?

PMID- 15951453
TI  - Sufficiently important difference: expanding the framework of clinical
      significance.
AB  - BACKGROUND: It is generally agreed that randomized controlled trials should be
      powered to detect small but clinically significant treatment effects. Toward
      these ends, minimal important difference (MID) was proposed as a benchmark for
      designing trials and for interpreting health-related quality-of-life instrument
      scores. MID was defined in 1989 as "the smallest difference in score in the
      domain of interest which patients perceive as beneficial and which would mandate,
      in the absence of troubling side effects and excessive cost, a change in the
      patient's management." OBJECTIVE: 1) To expand the idea of minimal clinically
      important difference so as to take into account harms as well as benefits. 2) To
      propose concepts and methods with which to do so. SUMMARY: The authors define
      sufficiently important difference (SID) as the smallest amount of patient-valued
      benefit that an intervention would require to justify associated costs, risks,
      and other harms. As a means toward estimation of SID, the authors propose benefit
      harm tradeoff methods, in which domains of benefit and harm are systematically
      traded off against each other and assessed in relation to the global decision of
      whether a treatment choice is worthwhile. Specific SID estimates can be used to
      power and interpret clinical trials or to inform health services research and/or
      public health policy. This article briefly describes the evolution of the
      important difference concept and outlines similarities and differences between
      MID and SID.

PMID- 15951454
TI  - Assessing the likelihood of an important clinical outcome: new insights from a
      comparison of clinical and actuarial judgment.
AB  - PURPOSE: To assess and rank the performance of different methods of predicting
      the probability of death following a specified surgical procedure. METHOD:
      Actuarial estimates of the probability of early mortality for 40 patients were
      derived from 2 sources: a large published surgical series and a smaller series
      from the center where surgery was performed. Surgeons and cardiologists also
      provided probability estimates for these patients. RESULTS: Estimates derived
      from the published literature were too optimistic and did not differentiate
      between patients more, or less, likely to die (i.e., failed to discriminate).
      Doctors' judgments were unbiased but failed to discriminate. Local actuarial
      estimates (influenced by only 1 or 2 variables) were unbiased, did discriminate,
      but exhibited more random variation. CONCLUSIONS: The preferred source of
      estimates depends upon which aspect of accuracy is of greatest importance.
      Differences in patient selection and error in the identification of risk factors
      mean that published results will not always appropriately predict surgical risk
      at other institutions. Risk stratification may be more robust when based on a
      small set of cross-validated predictors rather than a larger set of predictors
      that includes some whose reliability has not been confirmed.

PMID- 15951455
TI  - Mammographers' perception of women's breast cancer risk.
AB  - OBJECTIVE: To understand mammographers' perception of individual women's breast
      cancer risk. MATERIALS AND METHODS: Radiologists interpreting screening
      mammography examinations completed a mailed survey consisting of questions
      pertaining to demographic and clinical practice characteristics, as well as 2
      vignettes describing different risk profiles of women. Respondents were asked to
      estimate the probability of a breast cancer diagnosis in the next 5 years for
      each vignette. Vignette responses were plotted against mean recall rates in
      actual clinical practice. RESULTS: The survey was returned by 77% of eligible
      radiologists. Ninety-three percent of radiologists overestimated risk in the
      vignette involving a 70-year-old woman; 96% overestimated risk in the vignette
      involving a 41-year-old woman. Radiologists who more accurately estimated breast
      cancer risk were younger, worked full-time, were affiliated with an academic
      medical center, had fellowship training, had fewer than 10 years experience
      interpreting mammograms, and worked more than 40% of the time in breast imaging.
      However, only age was statistically significant. No association was found between
      radiologists' risk estimate and their recall rate. CONCLUSION: U.S. radiologists
      have a heightened perception of breast cancer risk.

PMID- 15951456
TI  - Can patients interpret health information? An assessment of the medical data
      interpretation test.
AB  - OBJECTIVE: To establish the reliability/validity of an 18-item test of patients'
      medical data interpretation skills. DESIGN: Survey with retest after 2 weeks.
      Subjects. 178 people recruited from advertisements in local newspapers, an
      outpatient clinic, and a hospital open house. RESULTS: The percentage of correct
      answers to individual items ranged from 20% to 87%, and medical data
      interpretation test scores (on a 0- 100 scale) were normally distributed (median
      61.1, mean 61.0, range 6-94). Reliability was good (test-retest correlation=0.67,
      Cronbach's alpha=0.71). Construct validity was supported in several ways. Higher
      scores were found among people with highest versus lowest numeracy (71 v. 36,
      P<0.001), highest quantitative literacy (65 v. 28, P<0.001), and highest
      education (69 v. 42, P=0.004). Scores for 15 physician experts also completing
      the survey were significantly higher than participants with other postgraduate
      degrees (mean score 89 v. 69, P<0.001). CONCLUSION: The medical data
      interpretation test is a reliable and valid measure of the ability to interpret
      medical statistics.

PMID- 15951457
TI  - Decreased use of adjuvant breast cancer therapy in a randomized controlled trial
      of a decision aid with individualized risk information.
AB  - OBJECTIVE: Oncology patients often seek involvement in their medical
      consultations. Such involvement is endorsed by most health care providers and
      mirrored in practice guidelines. However, oncologists exhibit great variation in
      how they provide patients with disease-relevant information, and many remain
      reluctant to do so at all. The authors examined the impact of a patient-specific
      decision aid on women's decisions about adjuvant therapy for breast cancer.
      METHOD: 386 women with breast cancer were randomized to receive either an
      informational pamphlet about adjuvant therapy (usual care) or a patient-specific,
      evidence-based decision aid about adjuvant therapy. The authors compared rates of
      adjuvant therapy between the groups controlling for age, education, marital
      status, race, tumor severity, and practice type of their physician (university
      based or community-based). RESULTS: Among women with low tumor severity, only 58%
      (35/60) of women in the decision aid group chose adjuvant therapy, compared to
      87% (33/38) of their counterparts in usual care (P<0.01). CONCLUSIONS: This study
      illustrates the important impact of medical decision aids on treatment choices,
      particularly for patients for whom treatment has little benefit. In the case of
      adjuvant therapy for breast cancer, providing individualized, evidence-based risk
      information for shared decision making resulted in fewer women with low tumor
      severity choosing adjuvant treatment.

PMID- 15951458
TI  - Is antibiotic prophylaxis for bacterial endocarditis cost-effective?
AB  - BACKGROUND: Antibiotic prophylaxis for bacterial endocarditis is recommended by
      the American Heart Association (AHA) before undergoing certain dental procedures.
      Whether such antibiotic prophylaxis is cost-effective is not clear. The authors'
      objective is to estimate the cost-effectiveness of predental antibiotic
      prophylaxis in patients with underlying heart disease. METHODS: The authors
      conducted a cost-effectiveness analysis using a Markov model to compare cost
      effectiveness of 7 antibiotic regimens per AHA guidelines and a no prophylaxis
      strategy. The study population consisted of a hypothetical cohort of 10 million
      patients with either a high or moderate risk for developing endocarditis.
      RESULTS: Prophylaxis for patients with moderate or high risk for endocarditis
      cost $88,007/quality-adjusted life years saved if clarithromycin was used.
      Prophylaxis with amoxicillin and ampicillin resulted in a net loss of lives. All
      other regimens were less cost-effective than clarithromycin. For 10 million
      persons, clarithromycin prophylaxis prevented 119 endocarditis cases and saved 19
      lives. CONCLUSION: Predental antibiotic prophylaxis is cost-effective only for
      persons with moderate or high risk of developing endocarditis. Contrary to
      current recommendations, our data demonstrate that amoxicillin and ampicillin are
      not cost-effective and should not be considered the agents of choice.
      Clarithromycin should be considered the drug of choice and cephalexin as an
      alternative drug of choice. The current published guidelines and recommendations
      should be revised.

PMID- 15951460
TI  - The cost-effectiveness of raising the legal smoking age in California.
AB  - Given evidence that most smokers start smoking before the age of 18 and that
      smokers who start earlier in life are less likely to quit, policies that reduce
      or delay initiation could have a large impact on public health. Raising the legal
      minimum purchase age of cigarettes to 21 may be an effective way for states to
      reduce youth smoking by making it harder for teens to buy cigarettes from stores
      and by reducing the number of legal buyers they encounter in their normal social
      circles. To inform the ongoing debate over this policy option in California, this
      study provides an evaluation of the cost-effectiveness of raising the state's
      legal smoking age to 21. Costs and benefits were estimated from a societal
      perspective using a dynamic computer simulation model that simulates changes to
      the California population in age, composition, and smoking behavior over time.
      Secondary data for model parameters were obtained from publicly available
      sources. Population health impacts were estimated in terms of smoking prevalence
      and the change in cumulative quality-adjusted life years (QALYs) to the
      California population over a 50-year period. Economic impacts were measured in
      monetary terms for medical cost savings, cost of law enforcement, and cost of
      checking identification. Compared to a status quo simulation, raising the smoking
      age to 21 would result in a drop in teen (ages 14-17) smoking prevalence from
      13.3% to 2.4% (82% reduction). The policy would generate no net costs, in fact
      saving the state and its inhabitants a total of $24 billion over the next 50
      years with a gain of 1.47 million QALYs compared to status quo. This research
      should prove useful to California's policy makers as they contemplate legislation
      to raise the state's legal smoking age.

PMID- 15951459
TI  - Optimal allocation of testing dollars: the example of HIV counseling, testing,
      and referral.
AB  - BACKGROUND: Health screening programs can be represented as a pathway of
      sequential processes: offering a test, obtaining consent, conducting the test,
      providing results, and linking to appropriate care. Using the example of HIV
      testing, the authors explore the optimal targeting of funds within this pathway.
      METHODS: The authors develop a microsimulation of HIV testing services and
      decompose the likelihood that an unidentified HIV-infected person will receive
      care into the probability of testing [P(test)] and the probability of follow-up
      [P(follow)] defined as returning for results and linking to care. The authors
      examine the clinical impact and cost-effectiveness of alternative investments in
      these component probabilities. RESULTS: At 1% undiagnosed HIV prevalence, cost
      effectiveness ratios for HIV testing cluster around $33,000/QALY (quality
      adjusted life year) gained. A program with a yield of 0.16 via P(test)=0.20 and
      P(follow)=0.80 has a cost-effectiveness ratio of $32,900/QALY compared with
      $36,300/QALY for a program where P(test)=0.80 and P(follow)=0.20. Interventions
      that improve the probability of success in later stages in the testing pathway
      [P(follow)] are more cost-effective than investments devoted to earlier stages
      [P(test)]. CONCLUSIONS: Equivalent pathway outcomes in a screening program do not
      confer equal value. Limited screening resources are best targeted toward
      returning for results and linkage among those already identified with disease
      rather than offering testing to additional people.

PMID- 15951461
TI  - How much does it cost to change the behavior of health professionals? A
      mathematical model and an application to academic detailing.
AB  - Several strategies have shown to be effective at enhancing the implementation of
      research findings in daily practice. These implementation strategies improve the
      delivery of preventive or therapeutic care by successfully educating health
      professionals. On the other hand, little is known about the costs of these
      implementation strategies. The goal of this article is to present a mathematical
      model that predicts implementation costs by using published data. As an important
      feature, the model portrays the relationship between the degree of treatment
      underuse and implementation costs. Two application examples of outreach programs
      for the prevention of stroke and coronary disease analyze the relevance of
      implementation costs with respect to the cost-effectiveness ratio and total
      costs. They demonstrate that implementation costs may have little impact on the
      cost-effectiveness ratio but may nevertheless be relevant to a 3rd-party payer
      who needs to stay within the budget and ensure that care is provided to a large
      underserved population. The model and its consideration of implementation costs
      may contribute to a more efficient use of health care resources.

PMID- 15951464
TI  - The cardiovascular toxicity of selective and nonselective cyclooxygenase
      inhibitors: comparisons, contrasts, and aspirin confounding.
AB  - The premature suspension of the Alzheimer Disease Anti-inflammatory Prevention
      (ADAPT) and the Adenoma Prevention with Celecoxib (APC) trials prompted intense
      review of the cardiovascular safety profile of selective and nonselective
      cyclooxygenase (COX) inhibitors. This article reviews the current state of
      selective COX-2 inhibitors, discusses the mechanistic evidence underlying the
      cardiovascular risk associated with selective COX-2 inhibition, outlines the
      pharmacodynamics of aspirin effects on platelets and the interference of
      propionic acid derivatives (ibuprofen and naproxen) with these effects, and poses
      that aspirin confounding may have led to the erroneous conclusion of naproxen
      associated adverse cardiovascular outcomes in the ADAPT trial. Finally,
      recommendations regarding selective COX-2 inhibitors and appropriate timing of
      aspirin coadministration with traditional NSAIDs are proposed in relevance to
      patient safety and future trial design.

PMID- 15951465
TI  - Rheumatoid arthritis: an overview of new and emerging therapies.
AB  - Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune
      disorder characterized by symmetric inflammation of synovial joints leading to
      progressive erosion of cartilage and bone. The aim of treatment is to mitigate
      joint destruction, preserve function, and prevent disability. The American
      College of Rheumatology guidelines for the treatment of RA recommend that newly
      diagnosed patients with RA begin treatment with disease-modifying antirheumatic
      drugs (DMARDs) within 3 months of diagnosis. Methotrexate remains the most
      commonly prescribed DMARD and is the standard by which recent new and emerging
      therapies are measured. Increasing knowledge regarding the immunologic basis of
      RA and advances in biotechnology have resulted in new, targeted biological
      therapies against proinflammatory cytokines that have dramatically changed the
      treatment paradigm and outcomes of patients with RA. This article reviews the
      pharmacological rationale underlying RA therapy, with a focus on currently
      available biological therapies and new therapies in development.

PMID- 15951466
TI  - The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in
      healthy male subjects.
AB  - The aim of the present study was to investigate the effect of a single dose of
      NN414 (a selective SUR1/Kir6.2 potassium channel opener). Sixty-four healthy male
      subjects were enrolled at 8 dose levels (0.625-12.5 mg/kg or placebo). The study
      consisted of a baseline day and a dosing day. NN414 or placebo was administered
      in the evening about 10 pm. On both study days, an oral glucose tolerance test
      (OGTT) was performed following an overnight fast (corresponding to 9 hours
      postdose), and glucose, insulin, glucagon, and growth hormone concentrations were
      determined. NN414 was well tolerated, with no clinically relevant changes in
      safety parameters, although there was an increase in gastrointestinal side
      effects. NN414 treatment lowered glucose during the OGTT and 24-hour insulin and
      glucose levels. In conclusion, a single dose of NN414 is associated with
      improvements in glucose-related parameters in healthy male subjects.

PMID- 15951467
TI  - Influence of coadministration on the pharmacokinetics of azimilide
      dihydrochloride and digoxin.
AB  - The influence of coadministration on digoxin and azimilide
      pharmacokinetics/pharmacodynamics was assessed in a randomized, 3-way crossover
      study in 18 healthy men. Serial blood and urine samples were obtained for
      azimilide and digoxin quantitation. Treatment effects on pharmacokinetics were
      assessed using analysis of variance. The relationship between azimilide blood
      concentrations and QT(c) prolongation was characterized by an E(max) model.
      Effects of coadministration on pharmacodynamics were assessed using a mechanistic
      based inhibition model. Azimilide pharmacokinetics was unaffected by digoxin,
      except for a 36% increase in CL(r) (P = .0325), with no change in CL(o). Digoxin
      pharmacokinetics was unaffected by azimilide, except for a 21% increase in C(max)
      (P = .0176) and a 10% increase in AUC(tau) (P = .0121). Digoxin coadministration
      increased the apparent EC(50) with no effect on E(max), consistent with
      competitive inhibition (K(i) = 0.899 ng/mL). The pharmacokinetic and
      pharmacodynamic changes observed upon coadministration were small and are not
      expected to be clinically important.

PMID- 15951468
TI  - Influence of everolimus on steady-state pharmacokinetics of cyclosporine in
      maintenance renal transplant patients.
AB  - To investigate possible interactions of the novel immunosuppressant everolimus
      with cyclosporine, a multicenter, randomized, double-blind, placebo-controlled,
      dose-escalating phase I study was performed. Everolimus regimens (0.75-10 mg/d)
      were administered for 28 days to stable renal allograft recipients receiving the
      microemulsion form of cyclosporine. Steady-state cyclosporine profiles were
      assessed at baseline on day 0 (cyclosporine alone) and on day 21 with everolimus
      on steady state. By day 21, mean dose-normalized cyclosporine AUC0-12 increased
      by 15% in patients receiving placebo. In everolimus-treated patients, mean
      increases in cyclosporine AUC0-12 ranged from 7% to 43%, which were not
      significantly different across all dosing cohorts including placebo. Linear
      regression of everolimus AUC on day 21 versus the increase in cyclosporine AUC0
      12 yielded a slope not significantly different from a horizontal line (P = ns).
      In conclusion, these results suggest that steady-state everolimus exposure over
      the wide range assessed in this study did not affect steady-state cyclosporine
      pharmacokinetics.

PMID- 15951470
TI  - Effect of hepatic impairment on the multiple-dose pharmacokinetics of ranolazine
      sustained-release tablets.
AB  - The effect of hepatic impairment on the pharmacokinetics of a sustained-release
      formulation of ranolazine and 3 major metabolites was investigated in an open
      label, parallel-group study. Ranolazine (875-mg loading dose followed by 500 mg
      every 12 hours for a total of 4 maintenance doses) was administered to subjects
      with mild (n = 8) or moderate (n = 8) hepatic impairment and a matched control
      group of healthy volunteers (n = 16). Moderate, but not mild, hepatic impairment
      significantly increased ranolazine steady-state area under the concentration-time
      curve (AUC0-12) by 76% (P < .001) and maximum plasma concentration C(max) by 51%
      (P < .01). The AUC0-12 ratio (metabolite/ranolazine) decreased for all
      metabolites in parallel with the degree of hepatic impairment. AUC0-infinity for
      the CYP3A substrate midazolam administered as a single dose was significantly
      correlated with ranolazine AUC0-12 at steady state (r2 = .33, P < .001). Over the
      time interval studied, ranolazine was well tolerated in healthy subjects and
      hepatically impaired subjects.

PMID- 15951469
TI  - Population pharmacokinetics of rituximab (anti-CD20 monoclonal antibody) in
      rheumatoid arthritis patients during a phase II clinical trial.
AB  - Rituximab is a B cell-depleting anti-CD20 chimeric IgGkappa monoclonal antibody
      being investigated for the treatment of rheumatoid arthritis. The purpose of this
      study was to develop a population pharmacokinetic model in rheumatoid arthritis
      patients. In addition, the final pharmacokinetic model was used to assess the
      variability in drug exposure (AUC0-infinity) for fixed versus body surface area
      based dosing. A total of 102 patients were included in this population
      pharmacokinetic analysis. A 2-compartment pharmacokinetic model described the
      data reasonably well. Body surface area and gender were the most significant
      covariates for both CL and Vc. Body surface area alone only explained about 19.7%
      of the total interindividual variability of CL. In a simulation study, body
      surface area-based dosing normalized drug exposure over a wide range of body
      surface area but did not seem to improve the predictability of rituximab AUC0
      infinity in rheumatoid arthritis patients. Therefore, no rationale for body
      surface area-based dosing for rituximab in rheumatoid arthritis patients was
      found.

PMID- 15951471
TI  - Pharmacokinetics of eplerenone after single and multiple dosing in subjects with
      and without renal impairment.
AB  - The influence of renal impairment on the pharmacokinetics of eplerenone following
      single and multiple dosing was evaluated. Subjects (n = 64) were stratified based
      on creatinine clearance values as follows: renal impairment (mild, moderate,
      severe), hemodialysis, and normal matches. Subjects received a single dose of
      eplerenone 100 mg on day 1 and then received 100 mg once daily on days 3 to 8.
      There were no statistically significant differences between any of the renal
      impairment groups and their matched-normal groups for area under the curve (AUC),
      C(max), or CL/F or CL/F/WT following either single or multiple dosing (P > or =
      .093). The inactive metabolite and inactive ring-opened form displayed greater
      AUCs in renal impairment. Hemodialysis removed approximately 10% of the
      eplerenone dose. Eplerenone 100 mg once daily was well tolerated in all groups.
      Considering that renal function had no significant effects on eplerenone CL/F and
      that eplerenone metabolites are inactive, no dose adjustment appears necessary in
      patients with renal dysfunction.

PMID- 15951473
TI  - An evaluation of an optimal sampling strategy for meropenem in febrile
      neutropenics.
AB  - Optimal sampling design with nonparametric population modeling offers the
      opportunity to determine pharmacokinetic parameters for patients in whom blood
      sampling is restricted. This approach was compared to a standard individualized
      modeling method for meropenem pharmacokinetics in febrile neutropenic patients.
      The population modeling program, nonparametric approach of expectation
      maximization (NPEM), with a full data set was compared to a sparse data set
      selected by D-optimal sampling design. The authors demonstrated that the D
      optimal sampling strategy, when applied to this clinical population, provided
      good pharmacokinetic parameter estimates along with their variability. Four
      individualized and optimally selected sampling time points provided the same
      parameter estimates as more intensive sampling regimens using traditional and
      population modeling techniques. The different modeling methods were considerably
      consistent, except for the estimation of CL(d) with sparse sampling. The findings
      suggest that D-optimal sparse sampling is a reasonable approach to population
      pharmacokinetic/pharmacodynamic studies during drug development when limited
      sampling is necessary.

PMID- 15951472
TI  - Effect of simulated microgravity on the disposition and tissue penetration of
      ciprofloxacin in healthy volunteers.
AB  - This study evaluated the effects of simulated microgravity (smuG) on the
      pharmacokinetics of ciprofloxacin. Six healthy volunteers participated in a
      crossover study to compare the pharmacokinetics of ciprofloxacin after a single
      250-mg oral dose in normal gravity (1G) and smuG. Plasma and urine samples were
      collected, and in vivo microdialysis was employed to obtain the free interstitial
      concentrations in the thigh muscle. Tissue penetration (f) was determined as the
      ratio of the free tissue area under the concentration versus time curve
      (AUC(tiss,free))/AUC(plasma,free). Plasma and free interstitial ciprofloxacin
      concentrations were simultaneously fit to a 1-compartment body model after
      correction for protein binding and tissue penetration. Total and free plasma
      concentrations were very similar in smuG and 1G. Tissue penetration in smuG (f
      =0.61 +/- 0.36) was slightly lower than in 1G (f =0.92 +/- 0.63); however, the
      difference was not significant. The authors conclude that the disposition of
      ciprofloxacin was not affected by simulated microgravity.

PMID- 15951474
TI  - Long-acting octreotide and prolonged-release lanreotide formulations have
      different pharmacokinetic profiles.
AB  - Single-dose pharmacokinetic (PK) profiles and multiple-dose PK modeling were
      compared for long-acting octreotide (20 or 60 mg) and prolonged-release
      lanreotide (90 or 120 mg) over 91 days; steady-state profiles were simulated. All
      treatments were well tolerated. Octreotide 20-mg profile showed increased
      concentration on day 1, lag from days 2 to 6, then prolonged plateau phase (days
      11-41); 60-mg PK was dose proportional. Lanreotide 90-mg profile showed C(max) on
      day 1 then elimination (apparent t1/2 25.5 days); 120-mg profile was
      underproportional. Steady-state PK of octreotide 20 mg/28 d suggested a C(mean)
      of 1216 rhog/mL (range, 1065-1585) with low fluctuation index (43%). Steady-state
      PK of lanreotide 90 mg/28 d suggested a C(mean) of 4455 rhog/mL (range, 2499
      9279) with high fluctuation index (152%). Long-acting octreotide had more
      predictable PK than prolonged-release lanreotide. Simulated steady-state profiles
      suggest long-acting octreotide could be optimized to meet individual patient
      needs. In contrast, prolonged-release lanreotide requires exposure constantly
      above the therapeutic target to enable monthly long-term therapy.

PMID- 15951475
TI  - Dipyridamole bioavailability in subjects with reduced gastric acidity.
AB  - Dipyridamole (DP) is an antiplatelet agent that shows decreased oral
      bioavailability with increased gastric pH that occurs with commonly prescribed
      antacids. An extended-release (ER) formulation of DP that employs tartaric acid
      to improve bioavailability of DP in the presence of elevated gastric pH was
      developed as a combination antiplatelet product with immediate-release aspirin.
      This crossover-designed study examined the relative bioavailability of DP from
      the composite product compared to conventional DP tablets during reduced gastric
      acidity. Gastric pH was increased (pH > 4.0) in 20 healthy subjects with
      lansoprazole (30 mg/d for 5 days). Dipyridamole systemic exposure over 12 hours
      was compared after oral administration of a single composite ER capsule (200 mg
      DP + 25 mg aspirin) versus two 100-mg conventional DP tablets given 6 hours apart
      combined with 81 mg aspirin. DP relative bioavailability was reduced 53% with
      conventional tablets compared to the composite buffered ER capsule in reduced
      gastric acid conditions. Peak DP plasma concentrations were 57% lower with
      immediate-release tablets compared to the composite formulation with high stomach
      pH. Substituting generic DP plus low-dose aspirin may be less effective than the
      buffered DP composite product in patients with concomitant antacid therapies.

PMID- 15951476
TI  - Hemodynamic effects of acute administration of atomoxetine and methylphenidate.

PMID- 15951478
TI  - DNA damage and osmotic regulation in the kidney.
AB  - Renal medullary cells normally are exposed to extraordinarily high interstitial
      NaCl concentration as part of the urinary concentrating mechanism, yet they
      survive and function. Acute elevation of NaCl to a moderate level causes
      transient cell cycle arrest in culture. Higher levels of NaCl, within the range
      found in the inner medulla, cause apoptosis. Recently, it was surprising to
      discover that even moderately high levels of NaCl cause DNA double-strand breaks.
      The DNA breaks persist in cultured cells that are proliferating rapidly after
      adaptation to high NaCl, and DNA breaks normally are present in the renal inner
      medulla in vivo. High NaCl inhibits repair of broken DNA both in culture and in
      vivo, but the DNA is rapidly repaired if the level of NaCl is reduced. The
      inhibition of DNA repair is associated with suppressed activity of some DNA
      damage-response proteins like Mre11, Chk1, and H2AX but not that of others, like
      GADD45, p53, ataxia telangiectasia-mutated kinase (ATM), and Ku86. In this
      review, we consider possible mechanisms by which the renal cells escape the known
      dangerous consequences of persistent DNA damage. Furthermore, we consider that
      the persistent DNA damage may be a sensor of hypertonicity that activates ATM
      kinase to provide a signal that contributes to protective osmotic regulation.

PMID- 15951479
TI  - Paracrine and differentiation mechanisms underlying stem cell therapy for the
      damaged kidney.

PMID- 15951480
TI  - Vitamin D.
AB  - The vitamin D endocrine system plays an essential role in calcium homeostasis and
      bone metabolism, but research during the past two decades has revealed a diverse
      range of biological actions that include induction of cell differentiation,
      inhibition of cell growth, immunomodulation, and control of other hormonal
      systems. Vitamin D itself is a prohormone that is metabolically converted to the
      active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. This vitamin D hormone
      activates its cellular receptor (vitamin D receptor or VDR), which alters the
      transcription rates of target genes responsible for the biological responses.
      This review focuses on several recent developments that extend our understanding
      of the complexities of vitamin D metabolism and actions: the final step in the
      activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)(2)D in
      renal proximal tubules, is now known to involve facilitated uptake and
      intracellular delivery of the precursor to 1alpha-hydroxylase. Emerging evidence
      using mice lacking the VDR and/or 1alpha-hydroxylase indicates both
      1,25(OH)(2)D(3)-dependent and -independent actions of the VDR as well as VDR
      dependent and -independent actions of 1,25(OH)(2)D(3). Thus the vitamin D system
      may involve more than a single receptor and ligand. The presence of 1alpha
      hydroxylase in many target cells indicates autocrine/paracrine functions for
      1,25(OH)(2)D(3) in the control of cell proliferation and differentiation. This
      local production of 1,25(OH)(2)D(3) is dependent on circulating precursor levels,
      providing a potential explanation for the association of vitamin D deficiency
      with various cancers and autoimmune diseases.

PMID- 15951481
TI  - Functional specificity of Sgk1 and Akt1 on ENaC activity.
AB  - Reabsorption of sodium by the epithelial sodium channel (ENaC) is essential for
      maintaining the volume of the extracellular compartment and blood pressure. The
      function of ENaC is regulated primarily by aldosterone, antidiuretic hormone
      [arginine vasopressin (AVP)], and insulin, but the molecular mechanisms that
      increase channel activity are still poorly understood. It has been proposed that
      the related serine/threonine kinases serum- and glucocorticoid-induced kinase
      (Sgk1) and protein kinase B (Akt) mediate activation of ENaC. Here, we addressed
      the question of whether there is functional specificity of these kinases for the
      activation of ENaC in epithelial cells of the distal renal tubule. We demonstrate
      that Akt does not increase ENaC function under basal conditions or after
      stimulation with aldosterone, insulin, or AVP. In contrast, under the same
      experimental conditions, Sgk1 increases ENaC activity by 10-fold. The effect of
      Sgk1 is additive to that of aldosterone, whereas, in the presence of active Sgk1,
      cells do not further respond to insulin or AVP. We conclude that, in cells
      expressing both kinases, modulation of ENaC activity is mediated by Sgk1 but not
      by Akt1.

PMID- 15951482
TI  - Increasing tolerance to ozone by elevating foliar ascorbic acid confers greater
      protection against ozone than increasing avoidance.
AB  - Ascorbic acid (Asc) is the most abundant antioxidant in plants and serves as a
      major contributor to the cell redox state. Exposure to environmental ozone can
      cause significant damage to plants by imposing conditions of oxidative stress. We
      examined whether increasing the level of Asc through enhanced Asc recycling would
      limit the deleterious effects of environmental oxidative stress. Plants
      overexpressing dehydroascorbate reductase (DHAR), which results in an increase in
      the endogenous level of Asc, were exposed to acute or chronic levels of ozone.
      DHAR-overexpressing plants had a lower oxidative load, a lower level of oxidative
      related enzyme activities, a higher level of chlorophyll, and a higher level of
      photosynthetic activity 24 h following an acute exposure (2 h) to 200 ppb ozone
      than control plants, despite exhibiting a larger stomatal area. Reducing the size
      of the Asc pool size through suppression of DHAR expression had the opposite
      effect. Following a chronic exposure (30 d) to 100 ppb ozone, plants with a
      larger Asc pool size maintained a larger stomatal area and a higher oxidative
      load, but retained a higher level of photosynthetic activity than control plants,
      whereas plants suppressed for DHAR had a substantially reduced stomatal area, but
      also a substantially lower level of photosynthetic activity. Together, these data
      indicate that, despite a reduced ability to respond to ozone through stomatal
      closure, increasing the level of Asc through enhanced Asc recycling provided
      greater protection against oxidative damage than reducing stomatal area.

PMID- 15951483
TI  - Origin and evolution of Kinesin-like calmodulin-binding protein.
AB  - Kinesin-like calmodulin-binding protein (KCBP), a member of the Kinesin-14
      family, is a C-terminal microtubule motor with three unique domains including a
      myosin tail homology region 4 (MyTH4), a talin-like domain, and a calmodulin
      binding domain (CBD). The MyTH4 and talin-like domains (found in some myosins)
      are not found in other reported kinesins. A calmodulin-binding kinesin called
      kinesin-C (SpKinC) isolated from sea urchin (Strongylocentrotus purpuratus) is
      the only reported kinesin with a CBD. Analysis of the completed genomes of Homo
      sapiens, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila
      melanogaster, and a red alga (Cyanidioschyzon merolae 10D) did not reveal the
      presence of a KCBP. This prompted us to look at the origin of KCBP and its
      relationship to SpKinC. To address this, we isolated KCBP from a gymnosperm,
      Picea abies, and a green alga, Stichococcus bacillaris. In addition, database
      searches resulted in identification of KCBP in another green alga, Chlamydomonas
      reinhardtii, and several flowering plants. Gene tree analysis revealed that the
      motor domain of KCBPs belongs to a clade within the Kinesin-14 (C-terminal
      motors) family. Only land plants and green algae have a kinesin with the MyTH4
      and talin-like domains of KCBP. Further, our analysis indicates that KCBP is
      highly conserved in green algae and land plants. SpKinC from sea urchin, which
      has the motor domain similar to KCBP and contains a CBD, lacks the MyTH4 and
      talin-like regions. Our analysis indicates that the KCBPs, SpKinC, and a subset
      of the kinesin-like proteins are all more closely related to one another than
      they are to any other kinesins, but that either KCBP gained the MyTH4 and talin
      like domains or SpKinC lost them.

PMID- 15951484
TI  - Purification and characterization of adenosine diphosphate glucose
      pyrophosphorylase from maize/potato mosaics.
AB  - Adenosine diphosphate glucose pyrophosphorylase (AGPase) catalyzes a rate
      limiting step in starch biosynthesis. The reaction produces ADP-glucose and
      pyrophosphate from glucose-1-P and ATP. Investigations from a number of
      laboratories have shown that alterations in allosteric properties as well as heat
      stability of this enzyme have dramatic positive effects on starch synthesis in
      the potato (Solanum tuberosum) tuber and seeds of important cereals. Here, we
      report the characterization of purified recombinant mosaic AGPases derived from
      protein motifs normally expressed in the maize (Zea mays) endosperm and the
      potato tuber. These exhibit properties that should be advantageous when expressed
      in plants. We also present an in-depth characterization of the kinetic and
      allosteric properties of these purified recombinant AGPases. These data point to
      previously unrecognized roles for known allosteric effectors.

PMID- 15951485
TI  - Mutational decay and age of chloroplast and mitochondrial genomes transferred
      recently to angiosperm nuclear chromosomes.
AB  - Transfers of organelle DNA to the nucleus established several thousand functional
      genes in eukaryotic chromosomes over evolutionary time. Recent transfers have
      also contributed nonfunctional plastid (pt)- and mitochondrion (mt)-derived DNA
      (termed nupts and numts, respectively) to plant nuclear genomes. The two largest
      transferred organelle genome copies are 131-kb nuptDNA in rice (Oryza sativa) and
      262-kb numtDNA in Arabidopsis (Arabidopsis thaliana). These transferred copies
      were compared in detail with their bona fide organelle counterparts, to which
      they are 99.77% and 99.91% identical, respectively. No evidence for purifying
      selection was found in either nuclear integrant, indicating that they are
      nonfunctional. Mutations attributable to 5-methylcytosine hypermutation have
      occurred at a 6- to 10-fold higher rate than other point mutations in Arabidopsis
      numtDNA and rice nuptDNA, respectively, revealing this as a major mechanism of
      mutational decay for these transferred organelle sequences. Short indels occurred
      preferentially within homopolymeric stretches but were less frequent than point
      mutations. The 131-kb nuptDNA is absent in the O. sativa subsp. indica or Oryza
      rufipogon nuclear genome, suggesting that it was transferred within the O. sativa
      subsp. japonica lineage and, as revealed by sequence comparisons, after its
      divergence from the indica chloroplast lineage. The time of the transfer for the
      rice nupt was estimated as 148,000 (74,000--296,000) years ago and that for the
      Arabidopsis numtDNA as 88,000 (44,000--176,000) years ago. The results reveal
      transfer and integration of entire organelle genomes into the nucleus as an
      ongoing evolutionary process and uncover mutational mechanisms affecting
      organelle genomes recently transferred into a new mutational environment.

PMID- 15951487
TI  - Comparison of tuber proteomes of potato varieties, landraces, and genetically
      modified lines.
AB  - Crop improvement by genetic modification remains controversial, one of the major
      issues being the potential for unintended effects. Comparative safety assessment
      includes targeted analysis of key nutrients and antinutritional factors, but
      broader scale-profiling or "omics" methods could increase the chances of
      detecting unintended effects. Comparative assessment should consider the extent
      of natural variation and not simply compare genetically modified (GM) lines and
      parental controls. In this study, potato (Solanum tuberosum) proteome diversity
      has been assessed using a range of diverse non-GM germplasm. In addition, a
      selection of GM potato lines was compared to assess the potential for unintended
      differences in protein profiles. Clear qualitative and quantitative differences
      were found in the protein patterns of the varieties and landraces examined, with
      1,077 of 1,111 protein spots analyzed showing statistically significant
      differences. The diploid species Solanum phureja could be clearly differentiated
      from tetraploid (Solanum tuberosum) genotypes. Many of the proteins apparently
      contributing to genotype differentiation are involved in disease and defense
      responses, the glycolytic pathway, and sugar metabolism or protein
      targeting/storage. Only nine proteins out of 730 showed significant differences
      between GM lines and their controls. There was much less variation between GM
      lines and their non-GM controls compared with that found between different
      varieties and landraces. A number of proteins were identified by mass
      spectrometry and added to a potato tuber two-dimensional protein map.

PMID- 15951486
TI  - Antisense suppression of deoxyhypusine synthase in tomato delays fruit softening
      and alters growth and development.
AB  - The effects of suppressing deoxyhypusine synthase (DHS) have been examined in
      tomato (Solanum lycopersicum cv UCT5). DHS mediates the first of two sequential
      enzymatic reactions that activate eukaryotic translation initiation factor-5A
      (eIF-5A) by converting a conserved Lys to the unusual amino acid, deoxyhypusine.
      DHS protein levels were suppressed in transgenic plants by expressing the 3'
      untranslated region of tomato DHS under regulation of the constitutive
      cauliflower mosaic virus promoter. Fruit from the transgenic plants ripened
      normally, but exhibited delayed postharvest softening and senescence that
      correlated with suppression of DHS protein levels. Northern-blot analysis
      indicated that all four gene family members of tomato eIF-5A are expressed in
      fruit, and that three are up-regulated in parallel with enhancement of DHS mRNA
      as the fruit begin to senesce and soften. Transgenic plants in which DHS was more
      strongly suppressed were male sterile, did not produce fruit, and had larger,
      thicker leaves with enhanced levels of chlorophyll. The activity of PSII was 2 to
      3 times higher in these transgenic leaves than in corresponding leaves of wild
      type plants, and there was also enhanced deposition of starch in the stems. The
      data collectively indicate that suppression of DHS has pleiotropic effects on
      growth and development of tomato. This may, in turn, reflect the fact that there
      is a single DHS gene in tomato and that its cognate protein is involved in the
      activation of four distinct isoforms of eIF-5A.

PMID- 15951488
TI  - Pectin methylesterase, a regulator of pollen tube growth.
AB  - The apical wall of growing pollen tubes must be strong enough to withstand the
      internal turgor pressure, but plastic enough to allow the incorporation of new
      membrane and cell wall material to support polarized tip growth. These essential
      rheological properties appear to be controlled by pectins, which constitute the
      principal component of the apical cell wall. Pectins are secreted as methylesters
      and subsequently deesterified by the enzyme pectin methylesterase (PME) in a
      process that exposes acidic residues. These carboxyls can be cross-linked by
      calcium, which structurally rigidifies the cell wall. Here, we examine the role
      of PME in cell elongation and the regulation of its secretion and enzymatic
      activity. Application of an exogenous PME induces thickening of the apical cell
      wall and inhibits pollen tube growth. Screening a Nicotiana tabacum pollen cDNA
      library yielded a pollen-specific PME, NtPPME1, containing a pre-region and a pro
      region. Expression studies with green fluorescent protein fusion proteins show
      that the pro-region participates in the correct targeting of the mature PME.
      Results from in vitro growth analysis and immunolocalization studies using
      antipectin antibodies (JIM5 and JIM7) provide support for the idea that the pro
      region acts as an intracellular inhibitor of PME activity, thereby preventing
      premature deesterification of pectins. In addition to providing experimental data
      that help resolve the significance and function of the pro-region, our results
      give insight into the mechanism by which PME and its pro-region regulate the cell
      wall dynamics of growing pollen tubes.

PMID- 15951489
TI  - A sphingolipid elicitor-inducible mitogen-activated protein kinase is regulated
      by the small GTPase OsRac1 and heterotrimeric G-protein in rice 1[w].
AB  - Mitogen-activated protein kinase (MAPK) cascades are activated in plants during
      responses to pathogens or to pathogen-derived elicitors and mediate intracellular
      stress responses. Here, we show that a rice (Oryza sativa) MAPK, OsMAPK6, was
      posttranslationally activated in a cell culture by a sphingolipid elicitor.
      Suppression of OsMAPK6 expression by RNA interference resulted in a strong
      reduction of pathogen-induced Phe ammonia-lyase mRNA, whereas the mRNA level of
      another rice MAPK, OsMAPK5a, was highly increased. Silencing of a small GTPase,
      OsRac1, by RNA interference or loss-of-function mutation (d1) of the
      heterotrimeric G-protein alpha-subunit gene resulted in a strong reduction of the
      OsMAPK6 protein levels and of kinase activation by a sphingolipid elicitor.
      Furthermore, coimmunoprecipitation experiments with OsRac1 and OsMAPK6 proteins
      showed that OsMAPK6 is closely associated with the active form of OsRac1, but not
      with inactive forms of OsRac1. These results indicate that these two G-proteins
      regulate an elicitor-inducible MAPK in rice at the protein level.

PMID- 15951491
TI  - Gene expression profiles of Blumeria graminis indicate dynamic changes to primary
      metabolism during development of an obligate biotrophic pathogen.
AB  - cDNA microarrays of Blumeria graminis f sp hordei transcript profiles during the
      asexual development cycle reveal the dynamics of global gene expression as the
      fungus germinates, penetrates, feeds on its host, and produces masses of conidia
      for dispersal. The expression profiles of genes encoding enzymes involved in
      primary metabolism show that there is a striking degree of coordinate regulation
      of some of the genes in the same pathway. In one example, genes encoding several
      glycolytic enzymes are significantly upregulated as mature appressoria form and
      also in infected epidermis, which contain fungal haustoria. In another example,
      mRNAs for lipid degrading enzymes are initially expressed at high levels in the
      conidia and the early germination stages and decrease significantly later. We
      discuss these results and draw inferences on the metabolic status of this
      obligate biotrophic fungus as it infects its host and completes its life cycle.

PMID- 15951492
TI  - Bovine TB: recommendations for premovement testing.

PMID- 15951490
TI  - Inhibition of de novo pyrimidine synthesis in growing potato tubers leads to a
      compensatory stimulation of the pyrimidine salvage pathway and a subsequent
      increase in biosynthetic performance.
AB  - Pyrimidine nucleotides are of general importance for many aspects of cell
      function, but their role in the regulation of biosynthetic processes is still
      unclear. In this study, we investigate the influence of a decreased expression of
      UMP synthase (UMPS), a key enzyme in the pathway of de novo pyrimidine synthesis,
      on biosynthetic processes in growing potato (Solanum tuberosum) tubers.
      Transgenic plants were generated expressing UMPS in the antisense orientation
      under the control of the tuber-specific patatin promoter. Lines were selected
      with markedly decreased expression of UMPS in the tubers. Decreased expression of
      UMPS restricted the use of externally supplied orotate for de novo pyrimidine
      synthesis in tuber tissue, whereas the uridine-salvaging pathway was stimulated.
      This shift in the pathways of UMP synthesis was accompanied by increased levels
      of tuber uridine nucleotides, increased fluxes of [(14)C]sucrose to starch and
      cell wall synthesis, and increased amounts of starch and cell wall components in
      the tubers, whereas there were no changes in uridine nucleotide levels in leaves.
      Decreased expression of UMPS in tubers led to an increase in transcript levels of
      carbamoylphosphate synthase, uridine kinase, and uracil
      phosphoribosyltransferase, the latter two encoding enzymes in the pyrimidine
      salvage pathways. Thus, the results show that antisense inhibition of the de novo
      pathway of pyrimidine synthesis leads to a compensatory stimulation of the less
      energy-consuming salvage pathways, probably via increased expression and activity
      of uridine kinase and uracil phosphoribosyltransferase. This results in increased
      uridine nucleotide pool levels in tubers and improved biosynthetic performance.

PMID- 15951498
TI  - Incidence and risk factors associated with exertional rhabdomyolysis syndrome in
      National Hunt racehorses in Great Britain.
AB  - A telephone survey of 51 National Hunt racing yards with 1140 horses in training
      was made in April and May 2003 to establish the incidence of exertional
      rhabdomyolysis syndrome during the previous year. A case-control study was used
      to investigate the risk factors for the syndrome in eight yards selected on the
      basis that cases had been confirmed by the analysis of serum muscle enzymes. The
      overall incidence of syndrome was 6.1 cases per 100 horses per year, and 55 per
      cent of the yards reported at least one case. The risk factors identified were
      sex, the average length of the training gallop, and the type of horse
      (steeplechaser, bumper/unraced or hurdler). There were no significant
      associations with the horses' temperament, age or Timeform rating.

PMID- 15951499
TI  - Persistence of Mycoplasma bovis infection in the mammary glands of lactating cows
      inoculated experimentally.
AB  - To study the course of clinical mycoplasma mastitis and investigate its potential
      for persistence, 10(8) colony-forming units (cfu) of an Irish isolate of
      Mycoplasma bovis was inoculated aseptically into the right fore teat canal of
      three lactating cows. M bovis rapidly colonised the infected quarters and grew
      exponentially to more than 10(10) cfu/ml within the first three days, and spread
      to other quarters of each of the three cows within five to 10 days. After periods
      of between 24 and 72 hours the infected quarters became distended and sensitive
      to touch, and their secretions changed from containing visible particles, to a
      seropurulent exudate, to an aqueous suspension of fine particles which formed a
      sediment after a sample was collected. M bovis-specific antibody levels increased
      to varying degrees in all three cows. Subsequently, the concentrations of
      mycoplasma decreased to less than 10(7) cfu/ml in two of the cows, but remained
      at more than 10(8) cfu/ml to the end of the lactation of the other cow.
      Apparently normal milk was secreted by one of the cows within a month of the
      challenge, and by the other two cows at the start of their next lactation.
      However, in two of the cows subclinical M bovis infection persisted through the
      dry periods and into their next lactations.

PMID- 15951500
TI  - Microscopic and clinical evidence for Anaplasma (Ehrlichia) phagocytophilum
      infection in Italian cats.
AB  - Fifteen cats from Italy with Ehrlichia-like inclusion bodies in their neutrophils
      were studied. They were diagnosed with Anaplasma (Ehrlichia) phagocytophilum
      infection on the basis of cytological observation of morulae within 1 to 21 per
      cent of their neutrophils, clinical signs characteristic of ehrlichiosis and
      their response to doxycycline. The predominant signs of disease were anorexia,
      lethargy, hyperaesthesia, muscle and joint pain, lameness, neck rigidity,
      lymphadenomegaly, gingivitis/periodontitis, conjunctivitis, weight loss,
      incoordination, pale mucous membranes and hyperglobulinaemia. The cat with
      inclusions in 21 per cent of its neutrophils had suffered arthralgia, tachypnoea,
      neck rigidity, vomiting and thrombocytopenia for four months, but recovered
      promptly after treatment with doxycycline.

PMID- 15951501
TI  - Phacoemulsification of bilateral cataracts in a loggerhead sea turtle (Caretta
      caretta).
AB  - An immature free-living loggerhead sea turtle (Caretta caretta) of unknown sex
      was found moribund off the coast of Wise Point, Virginia. It was suffering from
      cachexia and had bilateral hypermature cataracts which were treated by
      phacoemulsification under general anaesthesia. The surgery restored the turtle's
      vision and it was returned to the wild.

PMID- 15951502
TI  - Neuropathological lesions resembling equine grass sickness in rabbits.

PMID- 15951503
TI  - Conjoined twin piglets.

PMID- 15951504
TI  - Thrombosis of the ovarian and vaginal veins after caesarean section in a cow.

PMID- 15951505
TI  - Aneurysm of the ductus arteriosus in a heifer.

PMID- 15951506
TI  - Spastic paresis in calves.

PMID- 15951507
TI  - Shortage of farm animal vets.

PMID- 15951508
TI  - CPD provision for veterinary surgeons in practice.

PMID- 15951509
TI  - Role of the RCVS.

PMID- 15951510
TI  - Treating pet poultry.

PMID- 15951511
TI  - Undergraduate curriculum in veterinary schools.

PMID- 15951512
TI  - Protein length in eukaryotic and prokaryotic proteomes.
AB  - We analyzed length differences of eukaryotic, bacterial and archaeal proteins in
      relation to function, conservation and environmental factors. Comparing
      Eukaryotes and Prokaryotes, we found that the greater length of eukaryotic
      proteins is pervasive over all functional categories and involves the vast
      majority of protein families. The magnitude of these differences suggests that
      the evolution of eukaryotic proteins was influenced by processes of fusion of
      single-function proteins into extended multi-functional and multi-domain
      proteins. Comparing Bacteria and Archaea, we determined that the small but
      significant length difference observed between their proteins results from a
      combination of three factors: (i) bacterial proteomes include a greater
      proportion than archaeal proteomes of longer proteins involved in metabolism or
      cellular processes, (ii) within most functional classes, protein families unique
      to Bacteria are generally longer than protein families unique to Archaea and
      (iii) within the same protein family, homologs from Bacteria tend to be longer
      than the corresponding homologs from Archaea. These differences are interpreted
      with respect to evolutionary trends and prevailing environmental conditions
      within the two prokaryotic groups.

PMID- 15951513
TI  - cAMP-responsive element in TATA-less core promoter is essential for haploid
      specific gene expression in mouse testis.
AB  - Promoters, including neither TATA box nor initiator, have been frequently found
      in testicular germ cell-specific genes in mice. These investigations imply that
      unique forms of the polymerase II transcription initiation machinery play a role
      in selective activation of germ cell-specific gene expression programs during
      spermatogenesis. However, there is little information about testis-specific core
      promoters, because useful germ cell culture system is not available. In this
      study, we characterize the regulatory region of the haploid-specific Oxct2b gene
      in detail by using in vivo transient transfection assay in combination with a
      transgenic approach, with electrophoretic mobility shift and chromatin
      immunoprecipitation assays. Expression studies using mutant constructs
      demonstrate that a 34 bp region, which extends from -49 to -16, acts as a core
      promoter in an orientation-dependent manner. This promoter region includes the
      cAMP-responsive element (CRE)-like sequence TGACGCAG, but contains no other
      motifs, such as a TATA box or initiator. The CRE-like element is indispensable
      for the core promoter activity, but not for activator in testicular germ cells,
      through the binding of a testis-specific CRE modulator transcription factor.
      These results indicate the presence of alternative transcriptional initiation
      machinery for cell-type-specific gene expression in testicular germ cells.

PMID- 15951515
TI  - Thoughts on Senator William H. Frist's "Health Care in the 21st Century".

PMID- 15951514
TI  - Alteration of the nucleosomal DNA path in the crystal structure of a human
      nucleosome core particle.
AB  - Gene expression in eukaryotes depends upon positioning, mobility and packaging of
      nucleosomes; thus, we need the detailed information of the human nucleosome core
      particle (NCP) structure, which could clarify chromatin properties. Here, we
      report the 2.5 A crystal structure of a human NCP. The overall structure is
      similar to those of other NCPs reported previously. However, the DNA path of
      human NCP is remarkably different from that taken within other NCPs with an
      identical DNA sequence. A comparison of the structural parameters between human
      and Xenopus laevis DNA reveals that the DNA path of human NCP consecutively
      shifts by 1 bp in the regions of superhelix axis location -5.0 to -2.0 and 5.0 to
      7.0. This alteration of the human DNA path is caused predominantly by tight DNA
      DNA contacts within the crystal. It is also likely that the conformational change
      in the human H2B tail induces the local alteration of the DNA path. In human NCP,
      the region with the altered DNA path lacks Mn2+ ions and the B-factors of the DNA
      phosphate groups are substantially high. Therefore, in contrast to the histone
      octamer, the nucleosomal DNA is sufficiently flexible and mobile and can undergo
      drastic conformational changes, depending upon the environment.

PMID- 15951516
TI  - The power of collaboration.

PMID- 15951517
TI  - Prevention of nosocomial catheter-associated urinary tract infections through
      computerized feedback to physicians and a nurse-directed protocol.
AB  - Catheter-associated urinary tract infections (CAUTIs) represent the most common
      nosocomial infection. The authors' baseline rate of CAUTI for general medical
      service was elevated at 36 per 1000 catheter-days. The medical literature has
      consistently linked inappropriate catheter use with the development of CAUTI. The
      baseline data also revealed a high rate of inappropriate use of indwelling
      urinary catheters. Using the dual modalities of technology through prompts in the
      computerized order/entry system and handheld bladder scanners, as well as in
      combination with staff education and nurse empowerment, the authors were
      successful in reducing the use and duration of urinary catheters as well as the
      incidence of CAUTI. In subsequent data collection cycles over the following 2
      years, 81% reduction in device use and a 73% reduction in the clinical end point
      of nosocomial CAUTI (36/1000 catheter-days to 11/1000 catheter-days; P < .001)
      was demonstrated.

PMID- 15951518
TI  - The effect of web-based, personalized, osteoarthritis quality improvement
      feedback on patient satisfaction with osteoarthritis care.
AB  - To address gaps in the quality of care for osteo-arthritis, the authors developed
      a Web-based computer program to provide patients with personalized feedback
      designed to improve the quality of their osteoarthritis care. The current study
      was designed to examine satisfaction as well as the potential effects of the
      feedback on patients' perceptions of their osteoarthritis care by randomizing
      patients to use the site before or after they answered questions about the
      quality of their osteoarthritis care. On average, participants received 8.7
      recommendations to change their osteoarthritis care. Satisfaction with osteo
      arthritis care was similar between subjects in both groups. Most subjects
      believed that the Web site would help them get better care from their doctor
      (77.7%), and most would recommend it to others (94.3%). Overall, the Web site is
      well accepted and has no negative effect on patients' satisfaction with their
      osteo-arthritis care.

PMID- 15951519
TI  - Peer review and feedback can modify pain treatment patterns for emergency
      department patients with fractures.
AB  - Consecutive fracture patients presenting to an adult (AED) or pediatric trauma
      center (PED) or a community teaching hospital (CED) were reviewed for treatment.
      Physicians received individual and group feedback. Data were dichotomized by age,
      gender, race and insurance status. Logistic regression analysis modeled variables
      approaching statistical significance. A total of 1454 patients participated in
      the study. The aggregate initial treatment rate was 54%, with no subgroup
      differences. Significant improvements were seen in all sites/subgroups; the final
      aggregate treatment rate was 84% (P < .001). PED and CED patients were less
      likely to receive treatment than AED patients (odds ratios = 0.49, 0.68). After
      feedback, whites were treated more often than were non-whites (84% vs 71%, P <
      .0001); CED alone did not show this pattern (odds ratios = AED 4.14, PED 2.67,
      CED1.28). Patients at all sites received improved pain treatment in association
      with directed feedback. Race and treatment site were significant factors.

PMID- 15951520
TI  - Conceptual issues in the design and implementation of pay-for-quality programs.
AB  - This article identifies and discusses key conceptual issues in designing and
      implementing pay-for-quality programs. Such programs offer financial incentives
      to providers for achieving predefined quality targets. The purpose of the article
      is to provide health care professionals with a framework for designing,
      implementing, and evaluating pay-for-quality programs. Examples are drawn from
      the Rewarding Results demonstration project for which the authors serve as the
      national evaluation team.

PMID- 15951521
TI  - Clinical vignette-based surveys: a tool for assessing physician practice
      variation.
AB  - Clinical vignette-based surveys have been used for more than 30 years to measure
      variation in physicians' approaches to the diagnosis and treatment of patients
      with similar health problems. Vignettes offer advantages over medical record
      reviews, analysis of claims data, and standardized patients. A vignette-based
      survey can be completed more quickly than a record review or standardized patient
      program. Research has shown that vignette-based surveys produce better measures
      of quality of care than medical record reviews when used to measure differential
      diagnosis, selection of tests, and treatment decisions. Although standardized
      patients are preferred when measuring communication and physical examination
      skills, vignettes are more cost-effective than standardized patients when
      assessing clinical physicians' decision making. Vignettes offer better
      opportunities to isolate physicians' decision making and to control case-mix
      variation than do analyses of claims data sets. Clinical vignette-based surveys
      are simple and economical tools that can be used to characterize physicians'
      practice variation.

PMID- 15951523
TI  - Commentary: patient-centered health information technology.

PMID- 15951522
TI  - Validity of ICD-9-CM administrative data for determining eligibility for
      pneumococcal vaccination triggers.
AB  - The purpose of this study was to evaluate the efficacy of medical record
      administrative data as coded by the International Classification of Diseases,
      Ninth Revision, for triggering pneumococcal vaccination reminders of patients
      following discharge from a tertiary care adult teaching hospital. A retrospective
      computerized search was conducted using administrative discharge data to detect
      patients admitted to the medical teaching unit who met clinical criteria for
      pneumococcal vaccination according to Canadian immunization guidelines. For
      identification of persons eligible for vaccination, administrative discharge data
      showed a sensitivity of 83% (confidence interval [CI], 0.73-0.92) and a
      specificity of 78% (CI, 0.64-0.91), with a positive predictive value of 87% (CI,
      0.83-0.90) and a negative predictive value of 72% (CI, 0.58-0.86). The reasonably
      high specificity and sensitivity of diagnostic codes in administrative data could
      be used to trigger appropriate pneumococcal vaccination among eligible patients
      after hospital discharge.

PMID- 15951525
TI  - Analysis of glioma cell platinum response by metacomparison of two-dimensional
      chromatographic proteome profiles.
AB  - Successful clinical development of cancer treatments is aided by the development
      of molecular markers that allow the identification of patients likely to respond.
      In the case of broadly cytotoxic drugs, such as the multinuclear series of
      platinum chemotherapeutic agents that we are evaluating for the treatment of
      glioma, one route to marker identification is proteomic profiling. We are using
      the two-dimensional chromatography system, the ProteomeLab PF2D, to compare
      proteomic profiles of glioma cells in culture before and after drug treatment.
      The existing software tools allowed the rapid identification of peaks increased
      by treatment of a given drug as compared with control untreated cells. To compare
      across these pairs, we developed new software, called the MetaComparison Tool
      (MCT). The MCT uses the chromatographic characteristics of peaks as identifiers,
      an approach that was validated by mass spectrometry of two independent isolations
      of a peak, from cells that were treated with two different platinum compounds.
      The MCT made it possible to rapidly query whether a given peak responded to more
      than one treatment and so allowed the identification of peaks that were specific
      to a given drug. As a result, this analysis greatly reduced the list of peaks
      whose isolation and downstream analysis by mass spectrometry is warranted,
      accelerating the search for protein markers of response.

PMID- 15951528
TI  - Intestinal gas dynamics: mechanisms and clinical relevance.
AB  - Patients with functional gut disorders, irritable bowel disease, and related
      syndromes frequently attribute their symptoms to intestinal gas. While patients
      are usually convinced of their interpretation, the doctor has few arguments to
      confirm or refute it, and in this context intestinal gas has become a myth.
      Studies of intestinal gas dynamics have demonstrated subtle dysfunctions in
      intestinal motility. Hopefully, extension of these studies may help both in the
      classification of patients complaining of gas symptoms based on
      pathophysiological mechanisms, and in identification of objective markers to test
      mechanistically oriented treatment options.

PMID- 15951529
TI  - Does Mycobacterium avium subspecies paratuberculosis cause Crohn's disease?
AB  - Reassessing this persistent theory in light of advances in molecular microbial
      detection and genetic pathogenesis of disease.

PMID- 15951527
TI  - Human pancreatic exocrine response to nutrients in health and disease.

PMID- 15951530
TI  - Probiotics and barrier function in colitis.
AB  - Probiotic administration may exert a protective effect in colitis by preventing
      mucosal barrier disruption and influencing the extent of mucosal injury.

PMID- 15951531
TI  - Reinforcing the mucus: a new therapeutic approach for ulcerative colitis?
AB  - Luminal delivery of phosphatidyl rich phospholipids appears to reduce mucosal
      inflammatory activity in a high proportion of patients with chronically active
      ulcerative colitis. The simplicity and apparent safety of this therapeutic
      approach offers new insights into the importance of the mucus barrier in the
      pathogenesis and treatment of ulcerative colitis.

PMID- 15951533
TI  - Dyspeptic patients with visceral hypersensitivity: sensitisation of pain specific
      or multimodal pathways?
AB  - BACKGROUND AND AIMS: Patients with functional dyspepsia who have hypersensitivity
      to gastric distension have more prevalent pain, suggesting the presence of
      hyperalgesia. It is unclear whether this reflects activation of pain specific
      afferent pathways or multimodal afferent pathways that also mediate non-painful
      sensations. In the former case, hyperalgesia should occur when intensity of non
      painful sensations is still low. The aim of the study was to analyse whether the
      symptom profile during gastric dissentions in functional dyspepsia patients with
      hyperalgesia reflects sensitisation of pain specific or multimodal pathways.
      METHODS: Forty eight consecutive dyspeptic patients (35 female) underwent gastric
      sensitivity testing with a barostat balloon using a double random staircase
      protocol. At the end of every distending step, patients scored perception of
      upper abdominal sensations on a graphic 0-6 rating scale and completed visual
      analogue scales (VAS 0-100 mm) for pain, nausea, satiety, and fullness. The end
      point was a rating scale of 5 or more. RESULTS: Hypersensitivity was present in
      20 patients (40%); gastric compliance did not differ between normo- and
      hypersensitive patients. At maximal distension (score 5 or more), hypersensitive
      patients had significantly lower distending pressures and intra-balloon volumes,
      but similar VAS scores for pain, nausea, satiety, and fullness compared with
      normosensitive patients. In both normosensitive and hypersensitive patients,
      elevation of pain VAS scores with increasing distending pressures paralleled the
      elevation in VAS scores for nausea, satiety, and fullness. CONCLUSIONS:
      Hypersensitive dyspeptic patients reach the same intensity of painful and non
      painful sensations as normosensitive patients but at lower distending pressures.
      Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures
      that also induce intense non-painful sensations. These findings argue against
      isolated upregulation of pain specific afferents in functional dyspepsia patients
      with visceral hypersensitivity.

PMID- 15951532
TI  - Insulin resistance and steatosis in hepatitis C virus infection.
AB  - The relationship between hepatitis C virus (HCV), steatosis, and insulin
      resistance is genotype specific, and steatosis and insulin resistance are closely
      linked to the progression of liver disease in HCV infected patients.

PMID- 15951534
TI  - Expression of carbonic anhydrase 9 at the invasion front of gastric cancers.
AB  - BACKGROUND: Carbonic anhydrase IX (MN/Ca9) catalyses the reversible metabolism of
      carbon dioxide to carbonic acid and has also been linked to malignant
      transformation and hypoxia in various cancers. AIMS: To assess the expression and
      biological role of Ca9 in gastric cancer. METHODS: Using gastric cancer cell
      lines and tissues, we studied expression of Ca9 by western blot analysis,
      immunohistochemistry, and polymerase chain reaction. Biological changes after Ca9
      transfection and after treatment with 5'-azadeoxycytidine were also analysed in
      cancer cell lines. RESULTS: Non-cancerous tissues strongly expressed Ca9 with
      membranous localisation. In contrast, Ca9 expression was frequently lost in
      gastric cancers (p<0.001). However, gastric cancers that retained Ca9 expression
      in cancer cells exhibited a shorter postoperative survival (p = 0.028). In vitro
      analysis revealed that loss of Ca9 expression in gastric cancer cell lines was
      restored after treatment with 5'-azadeoxycytidine and was associated with
      increased invasion (p<0.01). Moreover, AGS cells transfected with Ca9 exhibited
      significantly increased cell proliferation (p<0.05). CONCLUSIONS: A subgroup of
      gastric cancers retain Ca9 expression in cancer cells at the invasion front.
      While loss of Ca9 expression is regulated in part by methylation, re-expression
      of Ca9 is associated with increased invasion, supporting the hypothesis that
      increased Ca9 expression may contribute to invasion and thus advanced disease and
      tumour progression in a subset of gastric cancers.

PMID- 15951535
TI  - Small bowel obstruction in a young woman.

PMID- 15951536
TI  - Growth, phenotype, and function of human intestinal mast cells are tightly
      regulated by transforming growth factor beta1.
AB  - BACKGROUND AND AIMS: Transforming growth factor beta1 (TGF-beta1) is expressed in
      the healthy human intestine and controls mucosal immune responses and
      inflammation by regulating the function of lymphocytes, macrophages, dendritic
      cells, and eosinophils. Here, we asked whether human intestinal mast cells (MC)
      might also be subject to immunoregulation by TGF-beta1. METHODS: MC were isolated
      from the intestinal mucosa, purified, and cultured in vitro in the presence of
      stem cell factor (SCF) with or without TGF-beta1. Growth characteristics,
      phenotype, and immunological mediator release of MC were analysed by reverse
      transcription-polymerase chain reaction, flow cytometry, immunocytochemistry,
      western blot, and different immunoassays, respectively. RESULTS: TGF-beta1 dose
      dependently (ED50 approximately = 0.1 ng/ml) inhibited SCF dependent growth of
      human intestinal MC by both enhancing apoptosis and decreasing proliferation. In
      parallel, TGF-beta1 increased the percentage of connective tissue-type MC
      expressing tryptase and chymase while downregulating expression of the receptors
      for IgE and SCF. Furthermore, TGF-beta1 dramatically changed the profile of
      mediators released by MC following IgE receptor crosslinking. Release of
      histamine, cysteinyl-leukotrienes, and tumour necrosis factor alpha was strongly
      reduced whereas prostaglandin D2 generation and cyclooxygenase 1 and 2 expression
      were upregulated by TGF-beta1. CONCLUSIONS: Our data indicate that TGF-beta1 acts
      as a novel potent inhibitor and modulator of human intestinal MC effector
      functions. The change in MC mediator release profile and protease expression
      induced by TGF-beta1 might be of relevance for the control of MC associated
      disorders of the intestine such as allergic reactions, Crohn's disease, irritable
      bowel syndrome, and parasitic infection.

PMID- 15951537
TI  - Glycoprotein (gp) 96 expression: induced during differentiation of intestinal
      macrophages but impaired in Crohn's disease.
AB  - BACKGROUND: The glycoprotein (gp) 96 links the adaptive with the innate immune
      system. It is a chaperone with a binding domain for peptides generated by
      proteasomal degradation. During cellular stress, peptide loaded gp96 can be
      released and presented to T cells by antigen presenting cells (APCs). METHODS:
      mRNAs from in vitro differentiated macrophages (iv mac) and normal intestinal
      macrophages (IMACs) were compared by subtractive hybridisation and Affymetrix
      GeneChip analysis. Differentiation induced expression of gp96 was investigated in
      the multicellular spheroid (MCS) model. In vivo gp96 protein expression was
      detected by double labelling immunohistochemistry of human colon and in the CD4+
      CD62L+ T cell transfer mouse model. RESULTS: Five of 76 clones obtained by
      subtractive hybridisation revealed >99% sequence homology to gp96. Affymetrix
      GeneChip analysis confirmed induction of gp96 in IMACs. Gp96 mRNA was detected in
      IMACs from normal and intestinal bowel disease mucosa. Induction of gp96 protein
      was observed after seven days in the MCS model of IMAC differentiation.
      Immunohistochemistry confirmed the presence of gp96 protein in IMACs in normal
      mucosa as well as in mucosa from patients with ulcerative colitis and
      diverticulitis. In mucosa from Crohn's disease (CD) patients, gp96 protein was
      not detectable. In the CD4+ CD62L+ T cell transfer mouse model, gp96 was
      verifiable in non-activated IMACs. CONCLUSION: Gp96 is induced during
      differentiation of normal IMACs but is not detected in IMACs in CD mucosa. As
      gp96 has been described as having a role in tolerance induction, this may be
      relevant for loss of tolerance against luminal bacteria found in CD patients.

PMID- 15951538
TI  - An unusual cause of rectal bleeding in a young woman.

PMID- 15951539
TI  - High prevalence of Mycobacterium avium subspecies paratuberculosis IS900 DNA in
      gut tissues from individuals with Crohn's disease.
AB  - BACKGROUND AND AIMS: Conflicting results exist about the presence of
      Mycobacterium avium subspecies paratuberculosis (MAP) specific IS900 DNA in
      Crohn's disease (CD) tissues. Therefore, we examined IS900 in a large number of
      gut samples from patients with CD (n = 100) and ulcerative colitis (UC, n = 100),
      and in non-inflamed control tissues (nIBD, n = 100). We hypothesised that IS900
      DNA detection might be associated with distinct clinical phenotypic
      characteristics in CD. METHODS: The prevalence of MAP DNA in surgically resected
      tissues was examined using a mechanical-enzymatic disruption technique and nested
      IS900 specific polymerase chain reaction (PCR). CD patients were stratified
      according to the criteria of the Vienna classification and other clinical
      characteristics. RESULTS: IS900 PCR detection rate was significantly higher in CD
      tissue samples (52%) than in UC (2%) or nIBD (5%) specimens (p<0.0001). In CD
      patients, IS900 DNA was detected in samples from both diseased small bowel (47%)
      as well as from the colon (61%). No firm association between MAP specific IS900
      detection rates and clinical phenotypic characteristics in CD could be
      established. However, corticosteroid medication constituted a factor which tended
      to have a negative influence on IS900 DNA detection rates in CD (p<0.01).
      CONCLUSIONS: The presence of MAP specific IS900 DNA is a predominant feature of
      CD. Therapeutic intervention against MAP might represent a potential target for
      disease mitigation in Crohn's disease.

PMID- 15951540
TI  - In vivo imaging of colitis and colon cancer development in mice using high
      resolution chromoendoscopy.
AB  - BACKGROUND: Mouse models of colitis and cancer are indispensable for our
      understanding of the pathogenesis of these diseases. In the past, mice had to be
      sacrificed in order to analyse colitis activity and tumour development. We have
      developed a safe method for high resolution endoscopic monitoring of living mice.
      METHODS: Mice developing colitis or colonic tumours were anaesthetised using
      avertine and repeatedly examined by endoscopy. A novel miniendoscope (1.9 mm
      outer diameter), denoted Coloview, was introduced via the anus and the colon was
      carefully insufflated with an air pump before analysis of the colonic mucosa. An
      extra working channel allowed the introduction of biopsy forceps or injection
      needles as well as surface staining with methylene blue in order to visualise the
      surface of the crypts and the pit pattern architecture. RESULTS: Endoscopic
      pictures obtained were of high quality and allowed monitoring and grading of
      disease. Scoring of colitis activity as well as tumour size and growth was
      possible. In addition, pit pattern analysis using chromoendoscopy permitted
      discrimination between inflammatory and neoplastic changes. Biopsies yielded
      enough tissue for molecular and histopathological analyses. CONCLUSIONS: In
      summary, chromoendoscopy in mice allows monitoring of the development of colitis
      and colon cancer with high resolution. Manipulations such as local injection of
      reagents or taking biopsies can be performed easily.

PMID- 15951541
TI  - Mucosal colonisation with Lactobacillus casei mitigates barrier injury induced by
      exposure to trinitronbenzene sulphonic acid.
AB  - BACKGROUND: Trinitrobenzene sulphonic acid (TNBS) induces chronic transmural
      inflammatory lesions in the rat colon. Injury is facilitated by barrier
      disruption and invasion of commensal bacteria. However, certain bacteria have
      shown anti-inflammatory properties in in vitro models. AIM: To investigate in
      vivo the anti-inflammatory effect of Lactobacillus casei DN-114 001. METHODS:
      Rats with a colonic segment excluded from faecal transit were surgically
      prepared. After washing the lumen with antibiotics, the excluded segment was
      recolonized (control group: standard flora of rat origin; test group: standard
      flora and L casei). Microbial colonisation was confirmed by culture of segment
      washing, and colitis was then induced by instillation of TNBS. One day after,
      intestinal lesions were blindly graded by macro- and microscopic scores, and
      myeloperoxidase activity measured in tissue homogenates. Translocation of
      bacteria to mesenteric lymph nodes, spleen and liver was investigated. RESULTS:
      Test rats showed a smaller area of mucosal injury than control rats (p<0.05).
      Maximum depth lesion scores were similar in both groups but myeloperoxidase
      activity was lower in test than in control rats (p<0.05). Remarkably, bacterial
      translocation was quantitatively lower (p<0.01) and less frequent (p<0.05) in
      test than in control rats. CONCLUSION: In rats colonised with L casei, mucosal
      injury, inflammatory response, and barrier disruption after TNBS challenge were
      attenuated. Bacterial communities colonising the mucosa can modify inflammatory
      responses to luminal challenges.

PMID- 15951542
TI  - Combined oral and enema treatment with Pentasa (mesalazine) is superior to oral
      therapy alone in patients with extensive mild/moderate active ulcerative colitis:
      a randomised, double blind, placebo controlled study.
AB  - BACKGROUND AND AIMS: Oral aminosalicylates are well established in the treatment
      of active mild/moderate ulcerative colitis (UC) when the disease is extensive
      (that is, beyond the splenic flexure). The majority of clinical symptoms relate
      to disease activity in the distal part of the colon and therefore this study was
      designed to investigate if adding a mesalazine enema to oral mesalazine has
      additional benefit for patients with extensive mild/moderate active UC. METHODS:
      A randomised double blind study was performed in 127 ambulatory patients. All
      received 4 g/day (twice daily dosing) oral mesalazine for eight weeks. During the
      initial four weeks, they additionally received an enema at bedtime containing 1 g
      of mesalazine or placebo. Disease activity was assessed using the ulcerative
      colitis disease activity index, with clinical and endoscopic signs at four and
      eight weeks. RESULTS: Remission was obtained in 44% (95% confidence interval (CI)
      31%, 58%) of the mesalazine enema group (Me) and in 34% (95% CI 21%, 49%) of the
      placebo enema group (Pl) at four weeks (p = 0.31) and in 64% (95% CI 50%, 76%) of
      the Me group versus 43% (95% CI 28%, 58%) of the Pl group at eight weeks (p =
      0.03). Improvement was obtained in 89% (95% CI 78%, 96%) of the Me group versus
      62% (95% CI 46%, 75%) of the Pl group at four weeks (p = 0.0008) and in 86% (95%
      CI 75%, 94%) of the Me group versus 68% (95% CI 53%, 81%) of the Pl group at
      eight weeks (p = 0.026). CONCLUSION: In patients with extensive mild/moderate
      active UC, the combination therapy is superior to oral therapy. It is safe, well
      accepted, and may be regarded as firstline treatment.

PMID- 15951543
TI  - An unusual cause of soft tissue infection.

PMID- 15951544
TI  - Retarded release phosphatidylcholine benefits patients with chronic active
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: We examined the hypothesis of an anti-inflammatory effect of
      phosphatidylcholine in ulcerative colitis. METHODS: A phase IIA, double blind,
      randomised, placebo controlled study was performed in 60 patients with chronic
      active, non steroid dependent, ulcerative colitis, with a clinical activity index
      (CAI) of > or = 4. Retarded release phosphatidylcholine rich phospholipids and
      placebo were administered at a dose of 6 g daily over three months. The primary
      end point was a change in CAI towards clinical remission (CAI < or = 3) or CAI
      improvement by > or = 50%. Secondary end points included > or = 50% changes in
      endoscopic activity index (EAI), histology, and quality of life scores. RESULTS:
      Induction of clinical remission (CAI < or = 3) as the primary outcome variable
      was attained by 16 (53%) patients in the phosphatidylcholine treated group
      compared with three (10%) in the placebo group (p<0.00001). The rate of clinical
      remission and CAI improvement was 90% in the phosphatidylcholine group and only
      10% in the placebo group. A median drop of seven points in the CAI score (70%
      improvement) was recorded in the phosphatidylcholine group compared with no
      change in the placebo group. Secondary end point analysis revealed concomitant
      drops in EAI and histology scores (p = 0.00016 and p = 0.0067 compared with
      placebo, respectively). Improvement in quality of life was reported by 16 of 29
      evaluated patients in the phosphatidylcholine group compared with two of 30 in
      the placebo group (p = 0.00005). CONCLUSION: Retarded release oral
      phosphatidylcholine is effective in alleviating inflammatory activity caused by
      ulcerative colitis.

PMID- 15951545
TI  - Identification of expandable human hepatic progenitors which differentiate into
      mature hepatic cells in vivo.
AB  - BACKGROUND: Liver diseases include a wide spectrum of both acute and chronic
      conditions which are associated with significant morbidity and mortality
      worldwide. Hepatocyte transplantation has therapeutic potential in the treatment
      of liver diseases, but its clinical use is hampered by the lack of donor tissue.
      Generation of hepatocytes in vitro from adult or fetal liver cell progenitors or,
      alternatively, identification of a progenitor population which in vivo can
      generate mature liver cells could solve this problem. METHODS: CD117+/CD34+/Lin-
      human fetal liver cells were isolated by magnetic cell sorting and expanded in
      culture. Both freshly isolated and in vitro expanded cells in various passages
      were studied for their ability to be functional in hepatic parenchyma following d
      galactosamine (GalN) induced injury in nude C57 black mice. RESULTS: Freshly
      isolated and in vitro expanded CD117+/CD34+/Lin- cells, when transplanted
      intrasplenically into GalN treated mice, morphologically and functionally
      differentiated into hepatocytes and cholangiocytes. Human specific albumin, alpha
      fetoprotein, cytokeratin 19, and antitrypsin mRNA were expressed in mouse liver.
      In addition, the human progenitor cells expressed glucose-6-phosphatase,
      glycogen, albumin, gamma glutamyl transpeptidase, and dipeptidyl peptidase IV
      after transplantation. Expanded cells in various passages maintained their
      capacity to differentiate into functional liver cells. CONCLUSIONS: Fetal liver
      CD117+/CD34+/Lin- progenitors and their progeny proliferated in vitro and also
      functionally differentiated into mature hepatic cells in an acute liver injury
      model. Successful in vitro expansion of liver progenitor cells provides a basis
      for developing cell therapy strategies, metabolic and toxicity testing systems,
      and may serve as a vehicle for gene therapy.

PMID- 15951546
TI  - First phenotypic description of transferrin receptor 2 knockout mouse, and the
      role of hepcidin.
AB  - BACKGROUND: Transferrin receptor 2 (TfR2) is a key molecule involved in the
      regulation of iron homeostasis. Mutations in humans cause type 3 haemochromatosis
      and a targeted mutation in mice leads to iron overload with a similar phenotype.
      We have previously described the generation of a complete TfR2-knockout (KO)
      mouse. AIMS: The aims of this study were to determine the phenotype and analyse
      expression of iron related molecules in the liver, duodenum, and spleen of
      homozygous TfR2-KO, heterozygous, and wild-type mice. METHODS: Serum and tissue
      iron levels were determined in 10 week old male mice. Expression of iron related
      mRNA transcripts were analysed in the liver, duodenum, and spleen using real time
      polymerase chain reaction. Expression of iron related proteins in the liver were
      analysed by immunoblotting and immunohistochemistry. RESULTS: Homozygous TfR2-KO
      mice had no TfR2 protein expression and developed significant iron overload
      typical of TfR2 associated haemochromatosis. In the liver of TfR2-KO mice there
      was no upregulation of hepcidin mRNA or prohepcidin protein in response to iron
      loading. CONCLUSIONS: Our results suggest that TfR2 is required for iron
      regulated expression of hepcidin and is involved in a pathway related to Hfe and
      hemojuvelin.

PMID- 15951547
TI  - Immune response towards lipid peroxidation products as a predictor of progression
      of non-alcoholic fatty liver disease to advanced fibrosis.
AB  - AIMS: Factors responsible for the progression of non-alcoholic fatty liver
      disease (NAFLD) to more severe liver injury are poorly understood. In the present
      study, we investigated the association between immune reactions triggered by
      oxidative stress and stage of NAFLD. METHODS: Titres of IgG against human serum
      albumin adducted with malondialdehyde (MDA-HSA) or arachidonic acid hydroperoxide
      (AAHP) and against oxidised cardiolipin (Ox-CL) were measured in 167 NAFLD
      patients with steatosis only (n = 79), steatohepatitis (n = 74), or steatosis
      plus cirrhosis (n = 14), and in 59 age and sex matched controls. RESULTS:
      Circulating IgG against lipid peroxidation products was significantly higher
      (p<0.001) in NAFLD patients than in controls. Oxidative stress dependent immune
      responses were not associated with obesity, type 2 diabetes, or with serum
      cholesterol, ferritin, or aminotransferase levels. Titres of lipid peroxidation
      related antibodies were also independent of the extent of steatosis and were
      similarly distributed in patients with and without necroinflammation. In
      contrast, the same antibodies were significantly increased in patients with
      advanced fibrosis or cirrhosis. Logistic regression analysis confirmed that anti
      MDA antibodies were independently associated with progression of NALFD and that
      NAFLD patients with titres of anti-MDA-HSA antibodies above the control threshold
      value had a threefold (relative risk 2.82 (95% confidence interval 1.35-5.90); p
      = 0.007) higher risk of having advanced fibrosis/cirrhosis than patients whose
      antibody titres were within the control range. CONCLUSIONS: These results
      indicate that the presence of immune reactions triggered by oxidative stress can
      be an independent predictor of progression of NAFLD to advanced fibrosis.

PMID- 15951548
TI  - The hepatic sympathetic nerve plays a critical role in preventing Fas induced
      liver injury in mice.
AB  - BACKGROUND: Although previous studies have shown that the hepatic sympathetic
      nerve controls various physiological functions in the liver, the role of this
      nerve in liver injury has yet to be clarified. AIMS: The purpose of this study
      was to elucidate the role of this nerve, based on our newly developed technique
      for selectively removing the activities of the hepatic sympathetic nerve.
      SUBJECTS AND METHODS: Male C57BL/6 mice were operated on for hepatic sympathetic
      denervation. Thereafter, mice were intravenously administered 0.25 or 0.35
      microg/g weight of the Fas agonist antibody, Jo-2, after which mortality by
      fulminant hepatitis was evaluated. Apoptosis in the liver was also examined by
      both terminal deoxynucleotidyl transferase mediated dUTP nick end labelling and
      caspase-3 assay. RESULTS: Mortality in sympathectomised mice was significantly
      higher than that in sham operated mice following administration of Jo-2. This
      result was also supported by apoptosis data in which sympathectomised livers
      exhibited a significant elevation in the number of apoptotic hepatocytes and
      caspase-3 activity after Jo-2 treatment compared with sham operated livers.
      Moreover, pretreatment with norepinephrine dose dependently inhibited the hepatic
      sympathectomy induced increase in mortality after Jo-2 injection. Antiapoptotic
      protein levels of FLICE inhibitory protein, Bcl-xL, and Bcl-2 in the liver were
      significantly lower in sympathectomised mice at one and two hours following Jo-2
      treatment than in sham operated animals. In addition, interleukin 6
      supplementation dose dependently suppressed the hepatic sympathectomy induced
      increase in mortality after Jo-2 treatment. CONCLUSIONS: These results suggest
      that norepinephrine released from the hepatic sympathetic nerve plays a critical
      role in protecting the liver from Fas mediated fulminant hepatitis, possibly via
      mechanisms including antiapoptotic proteins and interleukin 6.

PMID- 15951549
TI  - Chronic intermittent abdominal pain.

PMID- 15951550
TI  - Insulin resistance is a cause of steatosis and fibrosis progression in chronic
      hepatitis C.
AB  - BACKGROUND: Insulin resistance is a frequent feature of chronic hepatitis C.
      Whether insulin resistance could be the cause or consequence of steatosis and
      fibrosis is unknown. The ability of HCV genotype 3 to promote steatosis by itself
      provides an unique opportunity to answer this question. AIMS: The aim of the
      present study was to assess the relationships between insulin resistance,
      steatosis, and fibrosis according to genotype in 141 non-diabetic patients with
      biopsy proven non-cirrhotic chronic hepatitis C. METHODS: All patients had
      fasting serum glycaemia and insulinaemia measurements. Insulin resistance was
      evaluated using the homeostasis model assessment (HOMA IR) method. Liver
      steatosis was determined according to hepatitis C virus genotype (1 or 3).
      Logistic regression and multivariate regression analysis were used to identify
      variables independently associated with insulin resistance, fatty liver, and
      fibrosis. RESULTS: Although steatosis and fibrosis were more severe in genotype 3
      patients, median HOMA IR was significantly higher in patients with genotype 1
      related steatosis than in those with genotype 3 related steatosis (2.1 v 1; p =
      0.001). Independent risk factors for steatosis were insulin resistance in
      genotype 1 patients (p = 0.001) and viral load in genotype 3 patients (p =
      0.003). Among genotype 1 patients, independent parameters associated with insulin
      resistance were age (p = 0.04) and steatosis (p = 0.004). Steatosis was
      associated with more severe fibrosis whatever the genotype (p = 0.002). Among
      genotype 1 patients, although there was a significant relationship between
      circulating insulin level and fibrosis stage (p = 0.006), only steatosis and
      inflammatory score were independently associated with fibrosis. CONCLUSION: This
      study shows that insulin resistance is the cause rather than the consequence of
      steatosis and fibrosis in genotype 1 patients and that increased circulating
      insulin is a risk factor for fibrosis through insulin resistance induced
      steatosis.

PMID- 15951551
TI  - Response to interferon alfa is hepatitis B virus genotype dependent: genotype A
      is more sensitive to interferon than genotype D.
AB  - BACKGROUND AND AIMS: Current interferon alfa (IFN) treatment of chronic hepatitis
      B has limited efficacy. The role of hepatitis B virus (HBV) genotypes for
      response to IFN was investigated. PATIENTS AND METHODS: HBV genotype was
      determined by direct sequencing of the HBV X gene in 165 consecutive patients
      with chronic replicative hepatitis B treated with standard IFN. HBV genotype A or
      D was found in 144 cases. RESULTS: Sustained response (six months after
      treatment) to standard IFN therapy was higher in HBV genotype A compared with HBV
      genotype D infected patients (49% v 26%; p<0.005). Sustained response to IFN was
      46% versus 24% (p<0.03) in hepatitis B e antigen (HBeAg) positive hepatitis (n =
      99) and 59% versus 29% (p<0.05) in HBeAg negative hepatitis (n = 45) for HBV
      genotype A compared with HBV genotype D. HBeAg status had no negative impact on
      IFN response. Multivariate logistic regression identified HBV genotype A and high
      pretreatment alanine aminotransferase levels (>2 x upper limit of normal) as
      independent positive predictive parameters of IFN response. CONCLUSIONS: The
      present study indicates that HBV genotypes A and D are important and independent
      predictors of IFN responsiveness in chronic hepatitis B. HBV genotype adapted
      treatment regimens may further improve treatment efficacy in chronic hepatitis B.

PMID- 15951552
TI  - Suppression of haematopoiesis during therapy of chronic hepatitis C with
      different interferon alpha mono and combination therapy regimens.
AB  - BACKGROUND: Treatment of chronic hepatitis C with interferon (IFN)-alpha and
      ribavirin has haematotoxic effects. We evaluated the effects of four different
      IFN/IFN-ribavirin treatment regimens on haematopoiesis. METHODS: Haematopoiesis
      was studied in 133 patients with chronic hepatitis C receiving IFN-alpha2b alone
      (group A) or in combination with ribavirin (group B), pegylated IFN-alpha2a
      (group C), or pegylated IFN-alpha2b (group D) in combination with ribavirin.
      RESULTS: At week 4, haemoglobin levels were diminished in all groups receiving
      combination therapy. In the monotherapy group, haemoglobin decreased slightly
      after eight weeks. In all groups, haemoglobin remained diminished throughout
      therapy. In all patients, leucocytes (while blood cells) decreased after four
      weeks and remained low during treatment. Platelets (peripheral platelet count
      (PPC)) were decreased in all groups after four weeks and remained below baseline
      levels during therapy in group A, C, and D whereas in group B PPC recovered early
      and reached baseline levels at week 16 of therapy. Concomitantly with the
      decreases in haemoglobin and PPC, erythropoietin increased in all groups
      receiving combination therapy and thrombopoietin in all groups. Patients treated
      with pegylated IFN-alpha2a and those who received pegylated IFN-alpha2b
      combination therapy differed only in leucopoiesis, whereas erythropoiesis and
      thrombopoiesis were comparable. CONCLUSION: IFN-alpha based therapies are
      associated with a decrease in all three haematopoietic lineages, irrespective of
      the type of therapy used. The stronger suppressive effect of pegylated IFN
      alpha2a on leucopoiesis could be due to a dose effect. Overall, concentrations of
      endogenous haematopoietic growth factors are increased but can only partially
      alleviate haematotoxicity. Potential uses of exogenous haematopoietic growth
      factors and their impact on the virological response need to be explored.

PMID- 15951553
TI  - Nodular regenerative hyperplasia, portal vein thrombosis, and avascular hip
      necrosis due to hyperhomocysteinaemia.
AB  - A male patient with portal hypertension, portal vein thrombosis, spontaneous
      splenorenal shunt formation, and encephalopathy, thought to have post-hepatitis B
      cirrhosis, is described. His condition deteriorated and necessitated liver
      transplantation. In the explant liver, nodular regenerative hyperplasia with
      pronounced vascular lesions both in portal venules and in arterioles was found
      instead of classical cirrhosis. Two years post-transplant he developed bilateral
      ischaemic femur head necrosis. The three disorders (portal vein thrombosis,
      nodular regenerative hyperplasia, and ischaemic hip necrosis) seemed to be due to
      a common vasculopathy induced by hyperhomocyteinaemia. Genetic studies showed
      that he carried a mutation in the gene encoding for formation of
      methylenetetrahydrofolate reductase. Treatment with folic acid combined with
      pyridoxine (vitamin B6) and cyanocobalamin (vitamin B12) normalised his serum
      homocysteine levels.

PMID- 15951555
TI  - Prevention and management of duodenal polyps in familial adenomatous polyposis.

PMID- 15951556
TI  - Epithelial cells disseminate into the bone marrow of colorectal adenoma patients.

PMID- 15951554
TI  - Apoptosis: a mechanism of acute and chronic liver injury.

PMID- 15951557
TI  - Genetic evidence that juvenile nasopharyngeal angiofibroma is an integral FAP
      tumour.

PMID- 15951558
TI  - Smoking status in therapeutic trials in Crohn's disease.

PMID- 15951559
TI  - Evaluation of vascular signal in pancreatic ductal carcinoma using contrast
      enhanced ultrasonography: effect of systemic chemotherapy.

PMID- 15951560
TI  - Ferroportin disease due to the A77D mutation in Australia.

PMID- 15951561
TI  - HHV-8 positive, HIV negative disseminated Kaposi's sarcoma complicating steroid
      dependent ulcerative colitis: a successfully treated case.

PMID- 15951562
TI  - Binding of PTEN to specific PDZ domains contributes to PTEN protein stability and
      phosphorylation by microtubule-associated serine/threonine kinases.
AB  - The tumor suppressor phosphatase PTEN is a key regulator of cell growth and
      apoptosis that interacts with PDZ domains from regulatory proteins, including
      MAGI-1/2/3, hDlg, and MAST205. Here we identified novel PTEN-binding PDZ domains
      within the MAST205-related proteins, syntrophin-associated serine/threonine
      kinase and MAST3, characterized the regions of PTEN involved in its interaction
      with distinctive PDZ domains, and analyzed the functional consequences on PTEN of
      PDZ domain binding. Using a panel of PTEN mutations, as well as PTEN chimeras
      containing distinct domains of the related protein TPTE, we found that the PTP
      and C2 domains of PTEN do not affect PDZ domain binding and that the C-terminal
      tail of PTEN (residues 350-403) provides selectivity to recognize specific PDZ
      domains from MAGI-2, hDlg, and MAST205. Binding of PTEN to the PDZ-2 domain from
      MAGI-2 increased PTEN protein stability. Furthermore, binding of PTEN to the PDZ
      domains from microtubule-associated serine/threonine kinases facilitated PTEN
      phosphorylation at its C terminus by these kinases. Our results suggest an
      important role for the C-terminal region of PTEN in the selective association
      with scaffolding and/or regulatory molecules and provide evidence that PDZ domain
      binding stabilizes PTEN and targets this tumor suppressor for phosphorylation by
      microtubule-associated serine/threonine kinases.

PMID- 15951563
TI  - Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase
      independent mechanism.
AB  - Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase
      (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the
      retinoblastoma protein. In addition to its Cdk binding-dependent functions,
      cyclin D1 regulates cellular differentiation in part by modifying several
      transcription factors and nuclear receptors. The molecular mechanism through
      which cyclin D1 regulates the function of transcription factors involved in
      cellular differentiation remains to be clarified. The histone acetyltransferase
      protein p300 is a co-integrator required for regulation of multiple transcription
      factors. Here we show that cyclin D1 physically interacts with p300 and represses
      p300 transactivation. We demonstrated further that the interaction of the two
      proteins occurs at the peroxisome proliferator-activated receptor gamma
      responsive element of the lipoprotein lipase promoter in the context of the local
      chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in
      this interaction. The bromo domain and cysteine- and histidine-rich domains of
      p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was
      independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1.
      Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro.
      Microarray analysis identified a signature of genes repressed by cyclin D1 and
      induced by p300 that promotes cellular differentiation and induces cell cycle
      arrest. Together, our results suggest that cyclin D1 plays an important role in
      cellular proliferation and differentiation through regulation of p300.

PMID- 15951564
TI  - Sp1/Sp3-dependent regulation of human telomerase reverse transcriptase promoter
      activity by the bioactive sphingolipid ceramide.
AB  - In this study, the roles of Sp1/Sp3 transcription factors in the regulation of
      the activity of human telomerase reverse transcriptase (hTERT) promoter in
      response to ceramide were examined in the A549 human lung adenocarcinoma cells.
      The activity of the N-terminal truncated hTERT promoter, lacking the c-Myc
      recognition (E-box) region but containing multiple Sp1/Sp3 sites, was also
      significantly inhibited by C6-ceramide, indicating a role for ceramide in the
      regulation of Sp1/Sp3 function. Partial inhibition of Sp1 expression using small
      interfering RNA resulted in a significant inhibition of the hTERT promoter.
      Treatment with C6-ceramide inhibited the trans-activation function of
      overexpressed Sp1, whereas it induced the repressor effects of exogenous Sp3 on
      the hTERT promoter. The interaction between Sp1 and hTERT promoter DNA was
      significantly reduced in response to ceramide as assessed by chromatin
      immunoprecipitation analysis. In contrast, the promoter DNA-binding activity of
      Sp3 was slightly increased in response to C6-ceramide, resulting in the increased
      ratio of Sp3/Sp1 on the hTERT promoter, which was concomitant with the reduced
      recruitment of RNA polymerase II to the promoter. Furthermore, mutations of
      various Sp1/Sp3 recognition sequences significantly attenuated the activity of
      the promoter in the presence or absence of ceramide, demonstrating the importance
      of multiple Sp1/Sp3 recognition sites for the promoter activity. Mechanistically,
      the data demonstrated that C6-ceramide reduced the acetylation of Sp3 protein and
      partially blocked the activation of the hTERT promoter by the histone deacetylase
      inhibitor trichostatin A. The roles of endogenous long chain ceramide generated
      in response to gemcitabine in the inhibition of hTERT promoter activity and the
      regulation of Sp3 acetylation were also demonstrated.

PMID- 15951566
TI  - TWIN SISTER OF FT (TSF) acts as a floral pathway integrator redundantly with FT.
AB  - In Arabidopsis, several genetic pathways controlling the floral transition
      (flowering) are integrated at the transcriptional regulation of FT, LFY and SOC1.
      TSF is the closest homolog of FT in Arabidopsis. TSF expression was induced
      rapidly upon activation of CONSTANS (CO). The mRNA levels of TSF and FT showed
      similar patterns of diurnal oscillation and response to photoperiods: an evening
      peak, higher levels in long day (LD) than in short day (SD) conditions, and
      immediate up-regulation upon day-length extension. These observations suggest
      that TSF is a direct regulatory target of CO. tsf mutation delayed flowering in
      SD conditions and enhanced the phenotype of ft in both LD and SD conditions. TSF
      and FT also shared similar modes of regulation by FLC, an integrator of
      autonomous and vernalization pathways, and other factors such as EBS and PHYB.
      Consistently, TSF overexpression caused a precocious flowering phenotype
      independent of photoperiods or CO, or FLC. These observations suggest that TSF is
      a new member of the floral pathway integrators and promotes flowering largely
      redundantly with FT but makes a distinct contribution in SD conditions. TSF and
      FT seem to act independently of each other and of LFY, and partially upstream of
      SOC1. Interestingly, the expression patterns of TSF and FT in seedlings did not
      overlap, although both were expressed in the phloem tissues. Our work revealed
      additional complexity and spatial aspects of the regulatory network at the
      pathway integration level. We propose that the phloem is the site where multiple
      regulatory pathways are integrated at the transcriptional regulation of FT and
      TSF.

PMID- 15951567
TI  - The photosynthetic properties of rice leaves treated with low temperature and
      high irradiance.
AB  - Photosynthetic characteristics in rice (Oryza sativa L.) leaves were examined
      after treatment with low temperature (15 degrees C) and high irradiance (1,500
      micromol quanta m(-2) s(-1)). Decreases in quantum efficiencies in PSII (PhiPSII)
      and PSI (PhiPSI) and in the rate of CO2 assimilation were observed with a
      decrease in the maximal quantum efficiency of PSII (F(v)/F(m)) by simultaneous
      measurements of Chl fluorescence, P700+ absorbance and gas exchange. The
      decreases in PhiPSII were most highly correlated with those in CO2 assimilation.
      Although the initial (the activity immediately measured upon extraction) and
      total (the activity following pre-incubation with CO2 and Mg2+) activities of
      ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase (Rubisco) decreased
      slightly, the maximal activity (the activity following treatment with SO4(2-)) of
      Rubisco remained almost constant. These results indicate that the decrease in CO2
      assimilation rate with the decreasing F(v)/F(m) was not caused by a decrease in
      Rubisco activity but rather by a decrease in RuBP regeneration capacity which
      resulted from the decrease in the rate of the linear electron transport. On the
      other hand, the decrease in PhiPSI was very small and the ratio of PhiPSI to
      PhiPSII increased. The de-epoxidation state of xanthophyll cycle pigments also
      increased. Thus, the cyclic electron transport around PSI occurred in
      photoinhibited leaves.

PMID- 15951568
TI  - Sucrose synthase controls both intracellular ADP glucose levels and transitory
      starch biosynthesis in source leaves.
AB  - The prevailing model on transitory starch biosynthesis in source leaves assumes
      that the plastidial ADPglucose (ADPG) pyrophosphorylase (AGP) is the sole enzyme
      catalyzing the synthesis of the starch precursor molecule, ADPG. However, recent
      investigations have shown that ADPG linked to starch biosynthesis accumulates
      outside the chloroplast, presumably in the cytosol. This finding is consistent
      with the occurrence of an 'alternative' gluconeogenic pathway wherein sucrose
      synthase (SuSy) is involved in the production of ADPG in the cytosol, whereas
      both plastidial phosphoglucomutase (pPGM) and AGP play a prime role in the
      scavenging of starch breakdown products. To test this hypothesis, we have
      compared the ADPG content in both Arabidopsis and potato wild-type (WT) leaves
      with those of the starch-deficient mutants with reduced pPGM and AGP. These
      analyses provided evidence against the 'classical' model of starch biosynthesis,
      since ADPG levels in all the starch-deficient lines were normal compared with WT
      plants. Whether or not SuSy is involved in the synthesis of ADPG accumulating in
      leaves was tested by characterizing both SuSy-overexpressing and SuSy-antisensed
      transgenic leaves. Importantly, SuSy-overexpressing leaves exhibited a large
      increase of both ADPG and starch levels compared with WT leaves, whereas SuSy
      antisensed leaves accumulated low amounts of both ADPG and starch. These findings
      show that (i) ADPG produced by SuSy is linked to starch biosynthesis; (ii) SuSy
      exerts a strong control on the starch biosynthetic process; and (iii) SuSy, but
      not AGP, controls the production of ADPG accumulating in source leaves.

PMID- 15951569
TI  - Time-resolved mass spectrometry of tyrosine phosphorylation sites in the
      epidermal growth factor receptor signaling network reveals dynamic modules.
AB  - Ligand binding to cell surface receptors initiates a cascade of signaling events
      regulated by dynamic phosphorylation events on a multitude of pathway proteins.
      Quantitative features, including intensity, timing, and duration of
      phosphorylation of particular residues, may play a role in determining cellular
      response, but experimental data required for analysis of these features have not
      previously been available. To understand the dynamic operation of signaling
      cascades, we have developed a method enabling the simultaneous quantification of
      tyrosine phosphorylation of specific residues on dozens of key proteins in a time
      resolved manner, downstream of epidermal growth factor receptor (EGFR)
      activation. Tryptic peptides from four different EGFR stimulation time points
      were labeled with four isoforms of the iTRAQ reagent to enable downstream
      quantification. After mixing of the labeled samples, tyrosine-phosphorylated
      peptides were immunoprecipitated with an anti-phosphotyrosine antibody and
      further enriched by IMAC before LC/MS/MS analysis. Database searching and manual
      confirmation of peptide phosphorylation site assignments led to the
      identification of 78 tyrosine phosphorylation sites on 58 proteins from a single
      analysis. Replicate analyses of a separate biological sample provided both
      validation of this first data set and identification of 26 additional tyrosine
      phosphorylation sites and 18 additional proteins. iTRAQ fragment ion ratios
      provided time course phosphorylation profiles for each site. The data set of
      quantitative temporal phosphorylation profiles was further characterized by self
      organizing maps, which resulted in identification of several cohorts of tyrosine
      residues exhibiting self-similar temporal phosphorylation profiles, operationally
      defining dynamic modules in the EGFR signaling network consistent with particular
      cellular processes. The presence of novel proteins and associated tyrosine
      phosphorylation sites within these modules indicates additional components of
      this network and potentially localizes the topological action of these proteins.
      Additional analysis and modeling of the data generated in this study are likely
      to yield more sophisticated models of receptor tyrosine kinase-initiated signal
      transduction, trafficking, and regulation.

PMID- 15951570
TI  - The unstructured N-terminal tail of ParG modulates assembly of a quaternary
      nucleoprotein complex in transcription repression.
AB  - ParG is the prototype of a group of small (<10 kDa) proteins involved in accurate
      plasmid segregation. The protein is a dimeric DNA binding factor, which consists
      of symmetric paired C-terminal domains that interleave into a ribbon-helix-helix
      fold that is crucial for the interaction with DNA, and unstructured N-terminal
      domains of previously unknown function. Here the ParG protein is shown to be a
      transcriptional repressor of the parFG genes. The protein assembles on its
      operator site initially as a tetramer (dimer of dimers) and, at elevated protein
      concentrations, as a pair of tetramers. Progressive deletion of the mobile N
      terminal tails concomitantly decreased transcriptional repression by ParG and
      perturbed the DNA binding kinetics of the protein. The flexible tails are not
      necessary for ParG dimerization but instead modulate the organization of a higher
      order nucleoprotein complex that is crucial for proper transcriptional
      repression. This is achieved by transient associations between the flexible and
      folded domains in complex with the target DNA. Numerous ParG homologs encoded by
      plasmids of Gram-negative bacteria similarly are predicted to possess N-terminal
      disordered tails, suggesting that this is a common feature of partition operon
      autoregulation. The results provide new insights into the role of natively
      unfolded domains in protein function, the molecular mechanisms of transcription
      regulation, and the control of plasmid segregation.

PMID- 15951571
TI  - Structure of unliganded GRP94, the endoplasmic reticulum Hsp90. Basis for
      nucleotide-induced conformational change.
AB  - GRP94, the endoplasmic reticulum paralog of Hsp90, is regulated by adenosine
      nucleotides that bind to its N-terminal regulatory domain. Because of its weak
      affinity for nucleotides, the functionally relevant transition in GRP94 is likely
      to be between the unliganded and nucleotide-bound states. We have determined the
      structure of the unliganded GRP94 N-domain. The helix 1-4-5 subdomain of the
      unliganded protein adopts the closed conformation seen in the structure of the
      protein in complex with inhibitors. This conformation is distinct from the open
      conformation of the subdomain seen when the protein is bound to ATP or ADP. ADP
      soaked into crystals of the unliganded protein reveals an intermediate
      conformation midway between the open and closed states and demonstrates that in
      GRP94 the conversion between the open and closed states is driven by ligand
      binding. The direction of the observed movement in GRP94 shows that nucleotides
      act to open the subdomain elements rather than close them, which is contrary to
      the motion proposed for Hsp90. These observations support a model where ATP
      binding dictates the conformation of the N-domain and regulates its ability to
      form quaternary structural interactions.

PMID- 15951572
TI  - Structural and biochemical analysis reveal pirins to possess quercetinase
      activity.
AB  - Pirin is a recently identified eukaryotic protein implicated in transcriptional
      activation and apoptosis. Homologues of Pirin are highly conserved in both
      prokaryotes and eukaryotes, but their function remains poorly understood. We
      present here the crystal structure of the yhhW gene product, a putative Pirin
      homologue, from Escherichia coli and confirm its structural similarity to Pirin.
      The YhhW protein displays a bicupin fold with a single N-terminal metal
      coordination site. Molecular surface comparisons of YhhW and Pirin with
      structurally similar proteins suggested quercetin as a potential ligand. We
      demonstrate that both bacterial and human Pirins have quercetinase activity,
      which is inhibited by the addition of typical inhibitors of the quercetin 2,3
      dioxygenase reaction. We also demonstrate the release of carbon monoxide as a
      reaction product. This is the first report of enzymatic activity for any member
      of the Pirin family and may be an important connection to their roles in
      transcriptional regulation.

PMID- 15951573
TI  - Differential proteomic analysis of bronchoalveolar lavage fluid in asthmatics
      following segmental antigen challenge.
AB  - Allergic asthma is characterized by persistent airway inflammation and
      remodeling. Bronchoalveolar lavage conducted with fiberoptic bronchoscopy has
      been widely used for investigating the pathogenesis of asthma and other lung
      disorders. Identification of proteins in the bronchoalveolar lavage fluid (BALF)
      and their expression changes at different stages of asthma could provide further
      insights into the complex molecular mechanisms involved in this disease. In this
      report, we describe the first comprehensive differential proteomic analysis of
      BALF from both asthmatic patients and healthy subjects before and 24 h after
      segmental allergen challenge. Our proteomic analysis involves affinity depletion
      of six abundant BALF proteins, SDS-PAGE fractionation, protein in-gel digestion,
      and subsequent nano-LC-MS/MS analysis in conjunction with database searching for
      protein identification and semiquantitation. More than 1,500 distinct proteins
      were identified of which about 10% displayed significant up-regulation specific
      to the asthmatic patients after segmental allergen challenge. The differentially
      expressed proteins represent a wide spectrum of functional classes such as
      chemokines, cytokines, proteases, complement factors, acute phase proteins,
      monocyte-specific granule proteins, and local matrix proteins, etc. The majority
      of these protein expression changes are closely associated with many aspects of
      the pathophysiology of asthma, including inflammation, eosinophilia, airway
      remodeling, tissue damage and repair, mucus production, and plasma infiltration.
      Importantly a large portion of these proteins and their expression changes were
      identified for the first time from BALF, thus providing new insights for finding
      novel pathological mediators and biomarkers of asthma.

PMID- 15951575
TI  - Gestational diabetes mellitus -- time to treat.

PMID- 15951576
TI  - The Journal as a provider of continuing medical education.

PMID- 15951574
TI  - Effect of treatment of gestational diabetes mellitus on pregnancy outcomes.
AB  - BACKGROUND: We conducted a randomized clinical trial to determine whether
      treatment of women with gestational diabetes mellitus reduced the risk of
      perinatal complications. METHODS: We randomly assigned women between 24 and 34
      weeks' gestation who had gestational diabetes to receive dietary advice, blood
      glucose monitoring, and insulin therapy as needed (the intervention group) or
      routine care. Primary outcomes included serious perinatal complications (defined
      as death, shoulder dystocia, bone fracture, and nerve palsy), admission to the
      neonatal nursery, jaundice requiring phototherapy, induction of labor, cesarean
      birth, and maternal anxiety, depression, and health status. RESULTS: The rate of
      serious perinatal complications was significantly lower among the infants of the
      490 women in the intervention group than among the infants of the 510 women in
      the routine-care group (1 percent vs. 4 percent; relative risk adjusted for
      maternal age, race or ethnic group, and parity, 0.33; 95 percent confidence
      interval, 0.14 to 0.75; P=0.01). However, more infants of women in the
      intervention group were admitted to the neonatal nursery (71 percent vs. 61
      percent; adjusted relative risk, 1.13; 95 percent confidence interval, 1.03 to
      1.23; P=0.01). Women in the intervention group had a higher rate of induction of
      labor than the women in the routine-care group (39 percent vs. 29 percent;
      adjusted relative risk, 1.36; 95 percent confidence interval, 1.15 to 1.62;
      P<0.001), although the rates of cesarean delivery were similar (31 percent and 32
      percent, respectively; adjusted relative risk, 0.97; 95 percent confidence
      interval, 0.81 to 1.16; P=0.73). At three months post partum, data on the women's
      mood and quality of life, available for 573 women, revealed lower rates of
      depression and higher scores, consistent with improved health status, in the
      intervention group. CONCLUSIONS: Treatment of gestational diabetes reduces
      serious perinatal morbidity and may also improve the woman's health-related
      quality of life.

PMID- 15951577
TI  - The 'fifth vital sign'.

PMID- 15951578
TI  - Lower extremity amputation in Hong Kong.
AB  - OBJECTIVE: To evaluate the characteristics and outcome of patients undergoing
      lower extremity amputation in Hong Kong. DESIGN: Cohort study. SETTING:
      University teaching hospital, Hong Kong. PARTICIPANTS. One hundred and eighty
      four Chinese adults who underwent lower extremity amputation. MAIN OUTCOME
      MEASURES: Demographic data of the cohort, wound complication and revision
      amputation rates, prosthesis use, functional ambulation level and
      institutionalisation at postoperative 6 months, operative mortality, and long
      term survival. RESULTS: The majority of patients (83.1%) who underwent lower
      extremity amputation were aged over 60 years. Vascular occlusive disease was the
      most common underlying pathology, followed by infection. The wound complication
      and operative mortality rates were high. Only 43.0% of patients were able to
      resume community ambulation at 6 months and 40.7% became institutionalised. After
      high-level amputations, 22.3% managed to use a prosthesis. The median survival
      after lower extremity amputation was 1008 days. High-level amputation was
      associated with lower wound complication and revision amputation rates, but an
      inferior functional outcome and survival compared with foot amputation.
      CONCLUSIONS: Lower extremity amputation is associated with high morbidity and
      mortality, especially with high-level amputations. It places a heavy burden of
      care on patients, their families, the health care system, and society.
      Appropriate health care planning, provisions, and coordinated efforts at various
      levels are necessary to improve the situation. Major efforts must also be focused
      on preventing vascular occlusive disease and diabetes.

PMID- 15951579
TI  - Wire-guided excision of mammographic abnormalities.
AB  - OBJECTIVE: A review of wire-guided excision of abnormal lesions viewed on
      screening mammography. DESIGN. Retrospective review. SETTING: Regional hospital,
      Hong Kong. PATIENTS: Patients who underwent wire-guided excision of abnormalities
      visualised on screening mammography between 1999 and 2002. INTERVENTION: Wire
      guided excision. MAIN OUTCOME MEASURES: Biopsy rate and positive biopsy rate.
      RESULTS: A total of 65 patients underwent wire-guided excision of an abnormal
      lesion previously identified by screening mammography. Twenty-one were benign,
      two were lobular carcinoma in situ, and 42 were malignant. Of the latter, 30 were
      identified as ductal carcinoma in situ, and 12 as invasive breast cancer. Thirty
      eight of the 42 malignant cases required further treatment, and 24 of them
      underwent further operation. Radiological assessment of the 65 patients suggested
      that nine lesions were probably benign, 31 indeterminate, 20 suspicious, and five
      malignant. Malignancy was subsequently confirmed by histological examination in
      6, 20, 13, and 3 cases of the respective group of radiological assessment.
      CONCLUSION: The biopsy rate was approximately 3.7 per 1000 screened women, with
      results benign in 1.19 per 1000. The positive biopsy rate was 64.6%, and invasion
      was evident in 28.6%.

PMID- 15951580
TI  - The impact of urinary incontinence on quality of life among women in Hong Kong.
AB  - OBJECTIVE: To determine the prevalence of female urinary incontinence in Hong
      Kong and its impact on quality of life. DESIGN AND SETTING: Territory-wide
      telephone survey in Hong Kong. PARTICIPANTS: Hong Kong women aged 10 to 90 years
      accessed by fixed residential telephone lines between June 2001 and July 2002.
      MAIN OUTCOME MEASURES: The prevalence of urinary symptoms was assessed using
      telephone interview. The urinary symptoms investigated were as listed in a
      validated Chinese version of Urogenital Distress Inventory Short Form (UDI-6).
      The impact on quality of life was quantified using a validated Chinese version of
      Incontinence Impact Questionnaire Short Form (IIQ-7). RESULTS: There were 749
      valid respondents (response rate, 24.4%). Urinary symptoms were reported by 52%
      of women (95% confidence interval, 48.9-56.0%), of whom 12% believed it impaired
      their quality of life. Stress urinary incontinence was reported by 34% (95%
      confidence interval, 28.7-38.9%). Social (5.1%; 95% confidence interval, 2.8
      7.4%) and emotional (5.6%; 95% confidence interval, 3.3-7.9%) factors were the
      quality-of-life areas most impacted by urinary incontinence. CONCLUSIONS: Urinary
      symptoms are common among Hong Kong women. Quality of life is consequently
      impaired in 12% of affected women.

PMID- 15951581
TI  - Surveillance of acute flaccid paralysis in Hong Kong: 1997 to 2002.
AB  - OBJECTIVES: To describe the characteristics of patients reported with acute
      flaccid paralysis between 1997 and 2002, and to evaluate the performance of the
      acute flaccid paralysis surveillance system using indicators recommended by the
      World Health Organization. DESIGN: Retrospective study. SETTING: Department of
      Health, Hong Kong. PARTICIPANTS: Children aged younger than 15 years who were
      reported to the Department of Health between 1997 and 2002 with acute flaccid
      paralysis. RESULTS: Of 120 children with acute flaccid paralysis reported between
      1997 and 2002, 42% were younger than 5 years of age. None of the cases were acute
      poliomyelitis or polio-compatible. A neurological cause was identified in 67.5%
      of cases, of which the most common was Guillain-Barre syndrome (42%), followed by
      transverse myelitis (15%). All except one of the performance indicators
      consistently met World Health Organization requirements and thus demonstrated the
      effectiveness of the acute flaccid paralysis surveillance programme. The acute
      flaccid paralysis notification rate consistently exceeded 1.0 per 100 000
      population below 15 years of age. The requirement for adequate stool
      investigation was the single indicator that did not satisfy World Health
      Organization requirements. This highlighted the importance of maintaining
      physicians' awareness of acute flaccid paralysis surveillance. CONCLUSION: Hong
      Kong should remain vigilant for acute flaccid paralysis. The effective
      surveillance system and its evaluation may serve as a model for surveillance of
      other infectious diseases.

PMID- 15951582
TI  - A prospective evaluation of health-related quality of life in Hong Kong Chinese
      patients with chronic non-cancer pain.
AB  - OBJECTIVE: To evaluate the health-related quality of life in Hong Kong Chinese
      patients with chronic non-cancer pain. DESIGN: Prospective cross-sectional
      survey. SETTING: Regional public hospitals, Hong Kong. PATIENTS: Patients
      attending out-patient pain management clinics between 1 July 2002 and 28 February
      2003 were approached to complete a set of standardised questionnaires. MAIN
      OUTCOME MEASURES: Demographic profiles, treatment modality, litigation,
      compensation, social welfare status, Hospital Anxiety Depression Scale, and
      Medical Outcomes Survey short-form health survey (SF36). RESULTS: Data from 166
      patients were analysed. The median numeric pain rating score was 6 (interquartile
      range, 2-10). Work-related injury occurred in 34.3% of patients, while another
      34% were involved in pain-related litigation and 32% were receiving disability or
      unemployment benefit. Sixty-four percent of patients were managed by three or
      more disciplines, while 54.8% were also receiving complimentary alternative
      medical treatment, mainly traditional Chinese medicine (49.7%). The Hospital
      Anxiety Depression Score indicated clinical anxiety or depression in 71.1% of
      patients. All SF36 subscale scores were lower than the local population norm.
      Unemployed patients had higher depression scores (P = 0.005), while students or
      retirees had lower physical functioning scores (P = 0.004). Patients who were
      single had higher role emotion scores than those who were married or
      separated/widowed (P = 0.011). Logistic regression analysis showed that younger
      age (odds ratio = 0.95), being married (6.62), work-related injury (15.63) or
      higher general scores (1.03) were more likely to be associated with litigation.
      Social welfare benefit was associated with unemployment (3.39) and a lower level
      of physical functioning (0.98). CONCLUSION: There was a high prevalence of
      clinical anxiety, depression, and severe impairment in the health-related quality
      of life in Hong Kong Chinese patients with chronic non-cancer pain. Specific
      factors affected the health-related quality of life, likelihood of litigation,
      and social benefit.

PMID- 15951583
TI  - Japanese encephalitis in Hong Kong.
AB  - OBJECTIVES: To review past and present patterns of occurrence of Japanese
      encephalitis in Hong Kong and across Asia. A better understanding of the disease
      should facilitate the formulation of an effective strategic plan to prevent a
      future epidemic. DATA SOURCES: Report of local cases, and literature search of
      MEDLINE up to November 2004. STUDY SELECTION: Literature and data related to
      Japanese encephalitis. DATA EXTRACTION: Relevant information and data were
      reviewed by the authors. DATA SYNTHESIS: Since 16 July 2004, under the ordinance
      of Hong Kong, Japanese encephalitis has been a notifiable disease. In the past,
      Japanese encephalitis has reached epidemic proportions in Japan, South Korea, and
      some areas in China. It has spread globally and has a worldwide incidence of 35
      000 to 50 000 cases per year with 10 000 deaths. Mortality is about 30% and
      survivors often suffer serious long-term morbidity. In 2004, there were five
      local cases of Japanese encephalitis in Hong Kong. Subsequent serological
      surveillance of serum samples from 1547 local inhabitants revealed that 37 were
      positive, ie 2.4% of local inhabitants had been exposed to the Japanese
      encephalitis virus in the past. Most local inhabitants are immunologically naive
      to Japanese encephalitis virus. Most infections in endemic areas are
      asymptomatic. Patients with symptomatic Japanese encephalitis usually present
      with fever, headache, and confusion. Other signs include neurosis, poliomyelitis,
      and convulsion. Investigations including magnetic resonance imaging,
      electroencephalography, and single photon emission computed tomography are not
      specific. A definitive diagnosis depends on serological studies. Treatment is
      mainly supportive. CONCLUSIONS: The control of Japanese encephalitis in Hong Kong
      relies on an accurate surveillance system, vector control, vector avoidance, and
      vaccination of the at-risk population. At present, vaccination should be limited
      to travellers to endemic areas who would stay for longer than 1 month.

PMID- 15951584
TI  - Human infection by avian influenza A H5N1.
AB  - The Southeast Asian outbreak of the highly lethal avian influenza A H5N1
      infection in humans is unlikely to abate because of the enormous number of
      backyard farms providing poultry as the main source of food protein in developing
      countries. This increases the risk of the emergence of a reassortant pandemic
      influenza virus with improved human-to-human transmissibility. Currently triage
      of suspected cases by epidemiological risk factors remains the only practical way
      of case identification for laboratory investigation and infection control. The
      clinical usefulness of rapid diagnostic laboratory tests requires more vigorous
      evaluation. The lethality of this disease may reflect systemic viral
      dissemination, cytokine storm, or alveolar flooding due to inhibition of cellular
      sodium channels. The present circulating genotype Z is intrinsically resistant to
      amantadine and rimantadine. Prognosis may be improved by early treatment with a
      neuraminidase inhibitor with good systemic drug levels, and post-exposure
      prophylaxis for health care workers is recommended. The role of immunomodulators
      and other modalities of therapy requires evaluation in randomised controlled
      trials, with prospective monitoring of the viral load and cytokine profiles in
      various clinical specimens. In view of the high fatality of the disease, a
      combination of contact, droplet, and airborne precautions are recommended as long
      as resources allow despite the fact that the relative importance of these three
      modes in nosocomial transmission of avian influenza is still unknown.

PMID- 15951585
TI  - Performance of nurses in the Department of Health as service providers for a
      cervical screening programme.
AB  - A territory-wide cervical screening programme was launched in Hong Kong in March
      2004. Since 2002, 160 nurses from the Department of Health's Maternal and Child
      Health Centres have completed the training necessary to carry out the screening
      procedures. A clinical audit of their performance was carried out between 2002
      and 2004. A customer satisfaction survey revealed that 94% of respondents agreed
      or strongly agreed that they were satisfied with the cervical smear procedure
      performed by nurses. Since January 2003, all routine cervical screening tests at
      Maternal and Child Health Centres have been performed by nurses. The mean time
      required to complete a test is 7 minutes. The mean unsatisfactory smear rate for
      the year 2003 was 1.3%, well below the benchmark of 5% set by the Working Party
      on Quality Assurance of the Cervical Screening Task Force. The results of this
      survey confirm that nurses at Maternal and Child Health Centres are highly
      effective and efficient at taking smears and that this is well accepted by
      clients.

PMID- 15951586
TI  - Granulocytic sarcoma of the small bowel causing intestinal obstruction.
AB  - Granulocytic sarcomas of the small bowel are rare. They are discrete tumours of
      leukaemic myeloblasts and partially matured granulocytes that form in any part of
      the body. This disease is infrequently seen in patients with acute myeloid
      leukaemia, and rarely seen in patients without leukaemia. Here we report a case
      of small bowel obstruction due to granulocytic sarcoma of mid-ileum in a non
      leukaemic patient. We also review the literature on treatment and prognosis of
      this condition.

PMID- 15951587
TI  - Spinocerebellar ataxia type 6.
AB  - We report a 39-year-old woman with spinocerebellar ataxia type 6. She presented
      with ataxia and a 3-year history of progressive ataxia and recurrent falls. There
      was no relevant family history. Genetic tests revealed an expanded allele of 24
      CAG repeats at the spinocerebellar ataxia type 6 locus. This appears to be the
      first case reported in Hong Kong. As genetic testing becomes more widely
      available and clinical awareness increases, more such patients are expected to be
      diagnosed.

PMID- 15951588
TI  - Paradoxical deterioration during anti-tubercular treatment in a dialysis patient
      on maintenance steroid therapy.
AB  - We report a 38-year-old Chinese woman with lupus nephritis on peritoneal dialysis
      and long-term maintenance steroid therapy. This patient developed paradoxical
      deterioration during anti-tubercular therapy for tuberculous lymphadenitis. The
      deterioration resolved spontaneously without change to pharmacotherapy.
      Paradoxical deterioration that may spontaneously resolve is a potential
      complication of anti-tubercular treatment in patients on long-term renal
      replacement therapy.

PMID- 15951589
TI  - Epigastric pain in a patient with neurofibromatosis type 1.
AB  - Patients with neurofibromatosis type 1 are at increased risk of developing
      carcinoid tumours of the duodenum, particularly in the ampulla of Vater.
      Aggressive surgery with pancreatoduodenectomy is recommended for all ampullary
      carcinoid tumours because of their propensity to metastasise. We report a case of
      a 43-year-old woman with neurofibromatosis type 1, who presented with recurrent
      epigastric pain for 15 months. Evaluation using magnetic resonance
      cholangiopancreatography and side-viewing duodenoscopy revealed a submucosal
      tumour at the ampulla of Vater causing pancreatobiliary ductal obstruction and
      dilation. The ampullary tumour was overlooked initially by forward-viewing
      endoscopy. The patient subsequently underwent pancreatoduodenectomy. Histological
      examination of the surgically resected specimen confirmed the presence of a
      carcinoid tumour, with metastasis to peri-pancreatic lymph nodes. She remained
      asymptomatic 10 months after surgery.

PMID- 15951590
TI  - Obesity hypertension: the rationale for renin-angiotensin system blockade.

PMID- 15951591
TI  - The centrality of patient-physician relationship to medical professionalism: an
      ethical evaluation of some contemporary models.

PMID- 15951592
TI  - Two-port needlescopic cholecystectomy: a critical appraisal.

PMID- 15951593
TI  - More on phaeochromocytoma.

PMID- 15951595
TI  - Improvement of adenoidectomy for childhood snoring.

PMID- 15951596
TI  - [Cytometric assessment of apoptosis and aneuploidy in relation to survival time
      in osteosarcomas of children and adolescents].
AB  - Apoptosis programmed cell death takes place in response to many different
      stimuli, which include DNA damage. This is interest for therapeutic and
      prognostic purposes in neoplasms. Laboratory studies have shown that many anti
      cancer agents (including cytostatics) achieve their cytotoxic effect by inducing
      apoptosis. Flow cytometry methods have found application in identification and
      enumeration of apoptotic cells, which were used in the present study. The
      retrospective study concerning children and adolescents osteosarcomas has shown,
      that longer survival time correlated with higher apoptotic index (apoptotic cells
      in "pre-G1/G0" position of DNA histograms) in tumours after preoperative
      chemotherapy. Shorter survival time (up to 3 years) correlated with small
      apoptotic population and bigger aneuploid fraction. This suggests that response
      to applied chemotherapy of these osteosarcomas was relatively small. These
      preliminary results have shown, that estimation of the apoptotic population can
      be helpful in prognosis and effects of chemotherapy. It should be confirmed on
      fresh tumour material after preoperative chemotherapy and longer clinical
      observation.

PMID- 15951598
TI  - [Results of treatment for osteosarcoma in children and youth].
AB  - Bone tumours comprise about 5% of childhood neoplasms. Osteosarcoma is the most
      common sub-type and constitutes 60 % of all bone cancers. Incidence is similar in
      girls and boys and is increasing steeply with age. The most common localization
      of this tumour is long bones of the legs. Treatment including chemotherapy and
      surgery has led to an increase of the percentage of non-mutilating recovery. We
      present treatment results of 14 children with osteosarcoma.

PMID- 15951597
TI  - [Assessment of the correlation between proliferation defined by S-phase cell
      cycle and apoptosis after preoperative chemotherapy in osteosarcomas of children
      and adolescents].
AB  - Estimation of the S-phase of the cell cycle is applied to indicate the rate of
      cancer cells proliferation. This information is clinically useful, especially
      with the context of apoptosis (programmed cell death) stimulated by anticancer
      agents. The presented studies concerned above problems in children and
      adolescents osteosarcomas after preoperative chemotherapy. Flow cytometric method
      was used to analysis of S-phase cell cycle, aneuploidy and apoptosis (DNA
      histograms). The studies have shown that higher apoptotic index (percentage of
      apoptotic cells in "pre-G1/G0" position of DNA histograms), correlated with lower
      S-phase cell cycle and lower aneuploid fraction. It suggests that used
      chemotherapy treatment (Cisplatin, Adriamycin) induce apoptosis during S-phase
      cell cycle. Preliminary data are potentially important to predict clinical
      outcome after starting chemotherapy. This suggestion should be confirmed by
      estimation of other markers (early and late) of apoptosis.

PMID- 15951599
TI  - [Bone mineral density and markers of bone turnover in patients treated for
      malignant disease in childhood].
AB  - Development in diagnostic and therapeutic methods has led to increased survival
      rates in children with malignancies. The treatment with corticosteroids,
      methotrexate and irradiation may all cause reduction in bone mass. We assessed
      bone mineral density (BMD) and several parameters involved in bone formation in
      long-term survivors with a malignancy at completion of therapy. Total body and
      lumbar spine bone mineral densities (gram per cm2) were measured by dual energy x
      ray absorptiometry in 40 patients (age 12-27 yr; median 17.5 yr; 21 with acute
      lymphoblastic leukemias, 19 with other malignancies) from 3 to 13.9 years (median
      7 yr) after discontinuation of therapy. These results were compared with those
      from 473 healthy controls and expressed as a percentage of the age and sex
      matched control values (mean and standard deviation). Serum levels of
      osteocalcin, bone specific alkaline phosphatase, parathormone, 1.25
      dihydroxyvitamin D, urinary concentrations of deoxypyridinoline were determined
      as well as several specific markers of bone turnover. RESULTS: The total BMD and
      in the lumbar spine were not significantly reduced in survivors of childhood
      malignancies compared to the control population. No correlation was found between
      the BMD values and the cumulative doses and time of corticosteroids, administered
      Mtx, irradiation, duration of treatment, age at diagnosis. Duration of follow-up
      showed correlation with lumbar spine BMD. Serum markers of bone formation and
      resorption were in the normal range (expressed as standard deviation score
      relative to the age and sex-matched healthy population), bone turnover was not
      disturbed at the time of the study. CONCLUSION: We found no difference in bone
      mineralisation between our patients and the healthy population.

PMID- 15951600
TI  - [Vertebral compression fractures--the first manifestations of acute lymphoblastic
      leukemia of childhood].
AB  - We report 6 children, aged 4.5- 16 years, with acute lymphoblastic leukaemia with
      back pain, exacerbated by walking as the first symptom of disease. Collapse of
      the vertebral bodies at multiple levels was shown on imaging. The presented group
      had good prognosis. In densitometric examination of BMD (bone mineral density)
      was observed loss in the thoracic and lumbar vertebrae in 5 out of 6 children.
      Chemotherapy resulted in decrease of pain and spontaneous remodelling of the
      vertebrae.

PMID- 15951601
TI  - [Ewing's sacroma / PNET--the possibility to assure local control].
AB  - Ewing's sarcoma and PNET are more and more frequently submitted to surgical
      treatment, as this method of local therapy seems to offer a better chance for
      cure. Which method surgery or radiotherapy (RTx) is more mutilating in childhood,
      should be carefully considered. The aim of the report is to review the
      possibility of local resection and reconstruction in various sites of the tumour.
      PATIENTS: 12 patients with Ewing's sarcoma / PNET were submitted to the site
      specific surgical procedures and assessed for local control and function. All
      were pre-treated with CHT and continued that treatment after surgery. Four
      patients had fibular Ewing's sarcoma and all underwent subtotal fibulectomy. Long
      term complete remission (CR) was achieved in all. Two patients had Askin tumours;
      both developed pleural relapses distant to the primary tumour site. One patient
      had total scapulectomy (CR for 7 years). One patient had hemipelvectomy
      supplemented with RTx because of micro residue (CR for 10 years). Two patients
      were amputated: one for PNET of tibia invading nerves and vessels, another one
      for Ewing's sarcoma of femur. The first one developed pulmonary metastases and
      died one year later, the second one has been alive for 13 years but has badly
      accepted the prosthesis. Two patients with very extensive tumours of pelvis could
      never be operated on, they never achieved CR despite chemo- and radiotherapy and
      died. SUMMARY: Of 10 patients submitted to surgery 7 patients are alive and 4
      have an excellent functional result. Of the 2 patients in whom the tumour was
      inoperable neither is alive. It seems justified to recommend surgical resection
      of Ewing's sarcoma / PNET; satisfying reconstruction is usually feasible. RTx
      seems to have value rather as a method supplementing minor failures of surgery
      than as the only local treatment.

PMID- 15951602
TI  - [Immunophenotype of lymphoblastic leukaemia in children in relation to clinical
      symptoms and laboratory tests, preceding its diagnosis].
AB  - The aim of study was to compare the clinical picture and results of laboratory
      tests according to the acute lymphoblastic leukaemia (ALL) immunophenotype. The
      observation was carried out on a group of 67 patients treated in the IIIrd
      Department of Paediatrics and Department of Children Oncology in the Medical
      Academy of Bialystok from January 1994 to April 2001. This group consists of 4
      children with pro-B acute lymphoblastic leukaemia, 52 children with pre-B cell
      ALL, 1 child with B-cell acute lymphoblastic leukaemia and 9 children with T-cell
      acute lymphoblastic leukaemia. Haemorrhagic diathesis. splenomegaly, enlargement
      of peripheral lymph nodes as well as higher values of white blood cells count,
      blasts count, haemoglobin concentration, haematocrit and LDH activity were
      observed more frequently in patients with T-cell leukaemia than in others.

PMID- 15951603
TI  - [Clinical significance of erythrocyte sedimentation rate, C-reactive protein and
      serum lactate dehydrogenase levels in the diagnosis, prognosis and treatment
      monitoring of children suffering from cancer].
AB  - Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and serum lactate
      dehydrogenase (LDH) are non-specific biochemical markers, accompanying the growth
      of some neoplasms, both in adults and in children. The aim of this study was to
      determine the clinical value of ESR, CRP and LDH evaluation in the diagnosis,
      prognosis and monitoring of treatment among children suffering from cancer. 100
      children patients with acute leukaemia, Hodgkin's and non-Hodgkin's lymphoma,
      nephroblastoma and soft tissue sarcoma were included in the study, being compared
      to 30 healthy children of the control group. In oncological patients all the
      markers were estimated prospectively at 5 stages or the disease, i.e.: before
      treatment, during treatment -- in partial remission (PR) and after complete
      clinical remission was achieved (CR), after therapy and during the relapse or
      progression of cancer (PROG). The mean pre-treatment levels of analysed markers
      in cancer patients were significantly higher than in healthy children (p<0.001).
      The elevation of ESR, CRP and LDH was observed in 78.7, 50.8 and 72.1% of cases
      respectively. Good clinical response to antitumour therapy was paralleled with
      the significant decrease of pre-treatment ESR, CRP and LDH levels, but the values
      observed in CR, both while treatment and after therapy, did not return towards
      normal range. The progression of disease was accompanied by the increase of ESR,
      CRP and LDH levels, however only ESR and CRP values differed significantly in
      PROG as compared to the CR phase. Among analysed markers, only LDH level at
      diagnosis proved to be an independent prognostic factor for the overall survival
      rate. Three-year overall survival rate for patients with pre-treatment LDH level
      <1.5 x normal value (N) was 94% while for those with LDH >1.5 x N -- 67%. It has
      been demonstrated that ESR, CRP and LDH determinations in children suffering from
      cancer may serve as useful markers both in diagnostics and monitoring of the
      disease course. Moreover, the pre-treatment LDH level appeared to have an
      important role in prognosis of the overall survival rate.

PMID- 15951604
TI  - [Soft tissue sarcoma of the bladder and prostate. A report of the Polish
      Paediatric Solid Tumour Group (PPSTG)].
AB  - Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children younger
      then 15 years of age. The treatment of RMS localized in bladder or prostate still
      remains controversial. The aim of this study was analysis of treatment results in
      children with soft tissue sarcoma of bladder and prostate. From 1993 to 2001 the
      PPSTG has used three protocols to treat soft tissue sarcomas in children. The CWS
      91 regimen has been served to treat stage I-III and SIOP-IV Intergroup study in
      stage IV. Since 1996 the CWS-96 protocol for all patients in stage I-IV has been
      used. After biopsy confirmation of the diagnosis patients were treated with
      chemotherapy and subsequent surgery. Radiotherapy was administrated with total
      dose 32Gy v 44.5Gy v 48Gy. The group of 19 patients aged from 3 months to 18
      years with median age 6 y 4 m were evaluated. The median follow-up time was 42
      months. RMS-embryonal was diagnosed in 11 patients, RMS-alveolare in 4 and others
      types in 4. Sixteen patients presented clinical stage III and 3 stage IV The
      tumours were primarily localised in bladder in 16 patients and prostate in 3.
      Eight were tumours of volume bigger than 10 cm. After induction chemotherapy two
      patients received partial cystectomy, 5 complete cystectomy and 3 complete
      cystectomy with genitourinary reconstructive. Eight patients did not receive
      surgery. The most common treatment failure was isolated, local relapse in 8
      children particularly in patients with any second surgery. The EFS for all
      patients was 52% and for patients with localised RMS tumours 65%. Significant
      prognostic factors are the initial tumours volume, the lymph nodes infiltration
      and the response to the first chemotherapy cycle. Surgery is the most important
      procedure in local control of soft tissue sarcoma. Reconstructive options in poor
      and non responder patients can improve the EFS and life quality of those
      patients.

PMID- 15951605
TI  - [Giant fibroadenoma of the breast in a 14-year-old girl. Case report].
AB  - A 14-year old girl was admitted to the Department of Paediatric Surgery of the
      Regional Health Centre in Opole with 4-month lasting history of increasing
      enlargement of the left breast. Sonography revealed a not infiltrative tumour
      located in the left breast; fin e needle aspiration did not evidence any
      malignant cells. In consequence, marginal excision of this encapsulated tumour
      was performed. Final histopathological examination established the diagnosis of
      the "juvenile fibroadenoma of breast". The postoperative period was uneventful,
      and the cosmetic was accepted by the patient. The rarity of malignant tumours of
      breast in adolescents do not exclude such possibility, however it needs careful
      diagnostics and conservative approach to exclude malignancy. It seems important
      to perform an immediate plastic repair of correction alter surgical resection of
      the tumour.

PMID- 15951607
TI  - [Dry eye syndrome in children with cystic fibrosis].
AB  - BACKGROUND: Cystic fibrosis is a white Caucasian population specific disease,
      with autosomal recessive mode of inheritance. It is caused by mutations in the
      protein coding gene of chromosome 7, functioning as the cystic fibrosis
      transmembrane conductance regulator (CFTR), causing dysfunction of secretory
      glands in the alimentary tract, respiratory tract and in the eye. PURPOSE: The
      aim of the study was to evaluate the tear film stability in cystic fibrosis
      patients. PATIENTS AND METHODS: Fifteen patients with cystic fibrosis aged 8-23,
      mean age 13.05 +/- 3.45, and fifteen controls aged 8-21, mean age 13.56 +/- 3.45
      were examined. The tests included slit-lamp biomacroscopy, tear film break-up
      time, fluorescein staining and lissamine green staining. RESULTS: 54% Cystic
      fibrosis patients showed a statistically significant abnormal break-up time
      results. CONCLUSION: In cystic fibrosis patients we found low tear film
      stability. Fluorescine break-up time (FBUT) may be useful in the diagnosis of the
      dry eye in cystic fibrosis.

PMID- 15951606
TI  - [Intramuscular angiomyolipoma in children--own observations].
AB  - Angiomyolipoma (AGML) is a rare benign tumour usually located in the kidneys, but
      it can occur also in other sites -- e.g. in the skeletal muscles. This location
      requires differentiation from sarcomas and angiomas. The aim of the study is to
      assess the diagnostic and therapeutic methods applied in the management of
      patients with AGML. PATIENTS: five patients were treated for intramuscular AGML
      (1998-2001). Tumour localisation was as follows: intermediate head of vastus
      muscle of the femur, lateral head, medial head, occipital muscles of the head,
      and the interosteal muscles of the metatarsum. All patients complained of severe,
      localized pain; the tumour mass was usually small and hardly palpable. The biopsy
      was preceded by ultrasound examination with Colour-Doppler option and CT
      examination with "angio" option. After the result of the pathological examination
      of the biopsy specimen was obtained, surgery was performed. One cm of healthy
      tissue around the tumour was the required margin of excision. This was obtained
      in all cases but one. Pain relief was obtained in all patients; in one, local
      relapse occurred. CONCLUSION: AGML is a rare neoplasm in extra renal locations.
      Its appearance seems typical, with severe pain and only small deformation of the
      muscle. In this sub-group of patients, AMGL is located frequently in the femoral
      muscles. USG and CT imaging may correctly suggest the character of the tumour;
      however, the extent of treatment, should be decided after the biopsy
      histopathological report is known. MRI seems unnecessary when good quality
      Doppler-sonography and CT are available.

PMID- 15951608
TI  - [Prenatal diagnosis of cystic fibrosis in risk families in Poland--results of
      molecular analysis].
AB  - BACKGROUND: Cystic fibrosis is one of the most common genetic disorders in the
      Caucasian population, inherited as an autosomal recessive trait. Diagnosis of CF
      classifies the patient's family to the group of high genetic risk. In spite of
      the significant therapeutic advantages this disease is still the cause of preterm
      death of affected patients. One of the diagnostic tests that are offered to CF
      risk families is prenatal diagnostics of the disease. This kind of analysis may
      be performed in the first trimester of pregnancy and is based on the DNA analysis
      of the foetus. AIM: To sum up and analyse the results of CF prenatal diagnostic
      studies, in Poland, in the period 1990-2003. MATERIAL AND METHOD: In total 45
      tests in 38 risk families have been carried out. In case of 7 families in
      formative results have been obtained due to application of the polymorphic
      markers analysis. In the remaining cases molecular analysis of foetal DNA focused
      on identification of specific CFTR gene mutations has been carried out. RESULTS:
      In 16 cases the CF genotype was identified. The disease was excluded in 29
      foetuses. Some issues of genetic counselling in the context of the possibility of
      prenatal disease diagnosis have also been discussed.

PMID- 15951609
TI  - [Cystic fibrosis--a disease with many faces. The variable clinical picture versus
      the heterogeneity of molecular defect].
AB  - Cystic fibrosis (CF) is the most common genetic disorder in the Caucasian
      population with an autosomal recessive mode of inheritance. The disease is caused
      by mutations in the CFTR gene. So far, over 1300 of them have been identified.
      Primarily, the disease affects the epithelial cells of the airways, pancreas,
      intestines, gall bladder and sweat glands. However, cystic fibrosis is a
      clinically heterogeneous disorder. Especially the respiratory symptoms are
      significantly variable, even among patients with the same CFTR genotype.
      Therefore, there is an increasing interest in searching for the genetic modifiers
      of the clinical outcome in CF. This review presents the actual state of knowledge
      in terms of the potential genes-modifiers of the pulmonary form of cystic
      fibrosis.

PMID- 15951610
TI  - [Lamivudine treatment of chronic hepatitis B in children after treatment with
      interferon alfa--evaluation of the effectiveness of prolonged therapy].
AB  - AIM: To investigate the efficacy of lamivudine therapy in children with chronic
      hepatitis B who did not respond to interferon therapy in the past. MATERIAL AND
      METHODS: Thirty four children aged 7-16 were given lamivudine for 12 months.
      Because of replication of HBV, 21 children were treated for the next 12 months
      (up to 24 months). Lamivudine was given in the dose 3-5 mg/kg per day (maximum
      100 mg). Normalisation of aminotransferase, seroconversion HBe/anti-HBe and HBV
      DNA clearance were recognized as effective or promising prognosis of treatment.
      RESULTS: The response rate was 24% (8/34) and 29% (6/21) after 12 and 24 months
      respectively. In the first year of therapy the most significant was normalisation
      of aminotransferase, in the second year, seroconversion HBe/anti-HBe.
      CONCLUSIONS: 1. Lamivudine was effective in treatment of children with chronic
      hepatitis B, who did not respond to interferon alfa in the past. 2. Effectiveness
      of Lamivudine in longer period of treatment was increased from 24% at 12 months
      to 29% at 24 months. 3. Treatment of more than 12 months in children with
      replication hepatitis B virus, but initially normal aminotransferase, could cause
      Lamivudine resistance.

PMID- 15951611
TI  - [Current concepts of depression during adolescence].
AB  - Until the 1960-ties, there was considerable debate on whether or not depression
      exists before adulthood. Next, there were popular concepts, which emphasized that
      depression during adolescence is "normal" for that particular stage of
      development. From 1980-ties, adolescent depression is seen as the same problem as
      with adults. The diagnosis of depression in adolescents is based on adult
      diagnostic criteria. Today, there is a more generally accepted standard that
      adolescence depression is essentially the same phenomenon as adult depression but
      with some development specific modifications. As compared with adults,
      adolescents with depression demonstrate a more variable course. The adolescent
      with depression may exhibit somatic complaints, school difficulties and
      deconcentration rather than depressed mood. Three conceptualizations of
      depressive phenomena during adolescence have been presented in the literature:
      (1) depressed mood alone, (2) depressive syndrome, and (3) depressive disorders.
      Compas, Ey and Grant have compared and integrated different approaches to a
      synthesis that reflected a comprehensive model of depressive phenomena during
      adolescence. Depressed mood, syndromes, and disorders are integrated as 3 levels
      of depressive phenomena in a hierarchical and sequential model.

PMID- 15951612
TI  - [Incorrect trophoblast differentiation as a potential factor for
      preeclampsia/eclampsia development--a review].
AB  - Many authors stress that abnormal placental development may be an important
      pathogenetic factor in preeclampsia and in eclampsia. This review presents
      factors responsible for trophoblast differentiation and endometrium infiltration.
      It is discussed how in the pathogenesis of preeclampsia / eclampsia these factors
      may play an important part.

PMID- 15951613
TI  - [Lipodystrophy in HIV infected children].
AB  - Lipodystrophies are rare diseases with abnormal distribution of fat tissue and/or
      with metabolic changes. The consequence of metabolic abnormalities may be early
      atherosclerosis or ischaemic heart disease. During the last years lipodystrophy
      has been more often recognized in HIV infected, antiretroviral treated people.
      THE AIM was to estimate the prevalence of lipodystrophy in HIV infected children
      receiving Highly Active Antiretroviral Therapy (HAART). MATERIAL AND METHODS: 40
      children (age 3-16 years) were included in the study. An anamnesis (current
      complaints and family history) was taken and physical examination was carried
      out. Laboratory tests included: triglycerides, cholesterol and fractions,
      glucose. RESULTS: Medium time of HAART was 4 years. Lipodystrophy was found in
      9/40 children. Metabolic abnormalities and clinical manifestations were observed
      in all children with lipodystrophy. All of them were treated with Zerit, more
      often with Videx and Kaletra. 5/9 patients with and 5/31 without lipodystrophy
      had AIDS. Abnormal serum lipid concentrations were observed in 27/31 children
      without clinical symptoms of lipodystrophy. There was no significant connection
      with family history and current clinical stage. CONCLUSIONS: Advance of disease
      and HAART treatment (especially with Zerit, Videx and Kaletra) increases the risk
      of this syndrome. Metabolic abnormalities in HAART treated children are frequent,
      also in children without clinical manifestations of lipodystrophy. Estimated risk
      of metabolic abnormalities in children should influence the choice of therapeutic
      schedule or its modification.

PMID- 15951614
TI  - [Subtelomeric aberration as a cause of severe somatic and psychomotor retardation
      in a child with dysmorphic features and CNS defects].
AB  - Subtelomeric chromosome rearrangements are a significant cause of severe somatic
      and psychomotor retardation. Their incidence is estimated as 2.1/10000 liveborns
      and about 30-50% of the reported aberrations were familial. They result in a wide
      spectrum of clinical signs and most of reported cases are non-repeatable.
      Clinical verification of mentally retarded patients suspected of subtelomeric
      rearrangements requires a special molecular-cytogenetic method: subtelomeric
      fluorescence in situ hybridisation -- FISH. We present a case of submicroscopic
      subtelomeric aberration of chromosome 13 - der(13)t(X; 13) in a severely mentally
      retarded child with congenital defects and dysmorphic features. Detailed clinical
      characteristics of the proband as well as an attempt of a phenotype- genotype
      correlation of the identified chromosomal aberration were performed.

PMID- 15951615
TI  - [Low concentration of alpha-tocopherol in erythrocytes of atopic dermatitis
      patients].
AB  - BACKGROUND: It is suggested that the lipophilic antioxidant alpha-tocopherol
      could be useful in the management of atopic dermatitis (DA). AIM: The purpose of
      the study was to investigate vitamin E (alpha-tocopherol) status in children with
      DA. MATERIAL AND METHODS: 25 children with DA and 18 healthy controls were
      enrolled in this study (age: 1-9 years). The concentrations of alpha-tocopherol
      in plasma and in erythrocytes were determined by high-performance liquid
      chromatography. t-Student test was used in analysis of results. RESULTS: There
      were no differences between mean plasma alpha-tocopherol content (19.44 +/- 4,61
      mmol/l vs 18.74 +/- 3.38 mmol/l; p>0.05) and the ratio of alpha-tocopherol to
      total cholesterol in plasma (4.46 +/- 0.60 mmol/mmol vs 4.37 +/- 1,09 mmol/mmol;
      p>0.05) in patients and controls. Mean concentration of alpha-tocopherol in
      erythrocytes was significantly lower in children with DA (2.14 +/- 0.69 mmol/L)
      than in the control group (3.17 +/- 0.49 mmol/L, p<0.001). CONCLUSION: In
      children with DA, the homeostasis of alpha-tocopherol is changed. Decreased
      erythrocyte levels of the vitamin are probably due to the limited tissue reserve.
      The role of vitamin E in the pathogenesis and prevention of DA needs further
      investigations.

PMID- 15951616
TI  - [II. Pharmacogenetics--the future of modern pharmacology and genetics].
AB  - Pharmacogenetics is a scientific discipline connecting pharmacology and genetics.
      Its point of interest is an analysis of the variable, genetically determined
      patient's response to drugs. The basic discovery in this field was the
      elucidation of the heterogenic response of patients to the tuberculostatic drug -
      isoniazid. The new era of searching for the molecular background of the variable
      drugs metabolism has begun after identification, in the 50's, of the polymorphic
      variants of NAT2 gene. It encodes for N-acetyltransferase 2, an isoniazid
      metabolizing enzyme. The key catalysts of the biotransformation reactions are
      cytochrome P450 isoenzymes. Identification of the polymorphic variants of genes
      encoding these enzymes enabled an explanation of the heterogenic drugs tolerance.
      The current knowledge shows that the genetic defects that are responsible for
      variable pharmacological response concern not only genes encoding the
      metabolising enzymes but also transporter proteins and drug receptors. Due to
      achievements of the molecular genetics and putting into practice the modern
      bioinformatic technics new pharmacological opportunities have been created. It
      becomes possible to predict the patient's individual reactions and needs, without
      the necessity of treatment by "trial and error". Pharmacogenetics will allow to
      implement personalized therapy leading to safer and more effective drugs usage.
      Identification of the individual metabolising paths will reduce patient's
      exposition to the side effects of many drugs. In spite of many financial and
      logistic limitations there are chances of introducing the pharmacogenetic
      analysis -- as an obligatory step -- to the phases II and III of clinical trials
      by 2020.

PMID- 15951617
TI  - [Circulatory system in twin to twin transfusion syndrome].
AB  - BACKGROUND: Twin to Twin Transfusion Syndrome (TTTS) is a common and severe
      complication of monochorionic twin pregnancies associated with high perinatal
      loss rates and significant morbidity and morality in the surviving neonate. In
      recent years substantial progress has been made in understanding the
      pathogenesis, in the early diagnosis and methods of TTTS treatment, but many
      controversies still exist. Dynamic advance in the therapy of this foetal
      pathology considerably limited the morality: enlarging the number of neonates and
      children who require multidisciplinary intensive care. OBJECTIVE: The purpose of
      this study was to evaluate the circulatory system lesions in TITS during foetal
      life, after birth and in long term follow up. MATERIAL AND METHODS: We reviewed
      the available information on TTTS with special attention focused on circulatory
      system pathophysiology. CONCLUSIONS: A variety of cardiac system lesions seen in
      TTTS patients, many doubts and controversies concerning its aetiology and outcome
      create the necessity for further investigations including detailed circulatory
      system evaluation in the foetal life as well as in the neonatal period and long
      term follow-up.

PMID- 15951618
TI  - [Clinical course, diagnostic and therapeutic management of immune
      thrombocytopenic purpura in children].
AB  - PURPOSE: Immune thrombocytopenic purpura (ITP) is a common paediatric disease.
      Diagnosis of acute ITP is based on a platelet count less than 20 x 10(9)/L, with
      normal haemoglobin concentration and white blood cells count and absence of
      underlying conditions such as lymphoproliferative disorders or lupus
      erythematosus. The objective of this study was to present the clinical picture,
      the diagnostic procedures and therapeutic management of immune thrombocytopenic
      purpura in children treated in the Department of Paediatric Haematology and
      Oncology, Medical University, Lublin. PATIENTS AND METHODS: The authors analysed
      complete medical records of 107 patients treated for immune thrombocytopenic
      purpura. The investigated group consisted of 39 boys and 68 girls with age
      varying from 2 to 17 years and 7 months. In 44 patients the peripheral platelet
      count was less than 20 x 10(9)/L, in 24 children the platelet count ranged
      between 20-30 x 10(9)/L, in others it varied between 30-50 x 10(9)/L. In 48
      patients the physical examination revealed splenomegaly. RESULTS: l. In 72
      patients the cause of thrombocytopenia was established and included: in 24
      patients -- upper respiratory tract infection, in 16 patients -- viral infections
      (varicella, rubella, mumps), in 19 patients -- CMV infection, in 7 patients --
      EBV infection, in 6 patients -- contact with toxic substances; 2. In 5 patients
      thrombocytopenia episodes were diagnosed at least twice; 3. Typical presentation
      of acute ITP was observed in all patients; 4. Splenomegaly was confirmed in 48
      patients by diagnostic ultrasound. 5. Thirty patients recovered spontaneously
      without treatment; 6. Treatment of 65 patients resulted in complete recovery; 7.
      In 11 patients after 3 to 6 months of observation, splenectomy was performed.
      CONCLUSIONS: Therapeutic management of immune thrombocytopenic purpura in
      children treated in the Department of Paediatric Haematology and Oncology,
      Medical University, Lublin are comparable to the reports of Intercontinental
      Childhood ITP Study Group.

PMID- 15951619
TI  - Otolith mass asymmetries in the utricle and saccule of flatfish.
AB  - The otolith mass of the saccules and utricles of plaice, Pleuronectes platessa (n
      = 39) and turbot, Psetta maxima (n = 21) was measured using an electronic
      microbalance. In the right-eyed plaice, the left utricular otoliths were found to
      be significantly heavier than the right (p < 0.0001), whereas no significant
      difference was found between left and right saccular otoliths (p < 0.751). In the
      left-eyed turbot, both the right utricular and saccular otoliths were found to be
      significantly heavier (in both cases, p < 0.0001). While the gene and regulative
      protein responsible for the peripheral biomineralisation process have been
      identified, it remains unclear how the symmetry between the right and left
      otoliths in fish species is regulated. Here it is likely that an additional
      central mechanism is involved. It must be assumed that similar processes govern
      the systematic asymmetry observed in flatfish such as the plaice and turbot.
      Taken together these findings are strongly suggestive of concomitant CNS
      modification and metamorphic plasticity, presumably represented in genetic code.

PMID- 15951620
TI  - On the vestibular labyrinth of Brachiosaurus brancai.
AB  - The extensive remains of large sauropods, excavated in the Upper Jurassic layers
      of the Tendaguru region of Tanzania, East Africa by Janensch [15], include an
      intact fossil cast of a vestibular labyrinth and an endocast of the large
      Brachiosaurus brancai. The approximately 150 million year old labyrinth cast
      demonstrates clearly a form and organisation congruent in detail to those of
      extant vertebrate species. Besides the near-orthogonal arrangement of
      semicircular canals (SCCs), the superior and inferior branches of the vestibulo
      acoustic nerve, the endolymphatic duct, the oval and round windows, and the
      cochlea can be identified. The orientation of the labyrinth in the temporal bone
      is also equivalent to that of many extant vertebrates. Furthermore, the existence
      of the twelve cranial nerves can be identified from the endocast. The present
      study was initiated after the photogrammetric measurement of the skeleton volume
      of B. brancai [13] yielded a realistic estimate of body mass (74.42 metric tons).
      Dimensional analysis shows that body mass and average SCC dimensions of B.
      brancai generally fit with the allometric relationship found in previous studies
      of extant species. However, the anterior SCC is significantly larger than the
      allometric relationship would predict. This would indicate greater sensitivity,
      supporting the idea that the behavioural repertoire must have included much
      slower pitch movements of the head. These slower movements would most likely have
      involved flexion of the neck, rather than head pitching about the atlas joint.
      Pursuing the relationship between body mass and SCC dimensions further, the SCC
      frequency response is estimated by scaling up from the SCC dimensions of the
      rhesus monkey; this yields a range between 0.008-26 Hz, approximately one octave
      lower than for humans.

PMID- 15951621
TI  - Instantaneous rotation axes during active head movements.
AB  - Rotation axes were calculated during active head movements using a motion
      analysis system. The mean rotation axis for 1 Hz head pitch when seated was
      posterior (6 mm) and inferior (21 mm) to the interaural axis, shifting 16 mm
      downwards when standing. During seated 2 Hz head pitch the rotation axis was
      close to the interaural axis, shifting downwards 15 mm when standing. This
      downward shift suggests that cervical vertebrae were recruited during head pitch
      with the trunk unsupported. The proximity of the pitch axis to the otoliths
      implies minimal otolith activation during small-amplitude, high-frequency pitch
      rotations, such as those encountered during locomotion. The mean rotation axis
      for 1 Hz yaw rotation was located slightly posterior (10 mm) to the interaural
      axis at the midpoint between the vestibular labyrinths when both seated and
      standing. In addition, the orientation of the plane of yaw rotation relative to
      the stereotaxic horizontal plane (pitched 5 degrees nose-down) was essentially
      fixed in head coordinates, regardless of the pitch orientation of the head,
      suggesting that yaw movements occur about an axis restricted by the mechanical
      structure of the atlanto-axial joint. The results demonstrate that the
      instantaneous rotation axes technique overcomes the inherent instability of the
      helical-axis representation for small head movements.

PMID- 15951622
TI  - Effect of angular acceleration on the localization performance of a remembered
      target.
AB  - Both the influence of a remembered "earth-fixed" target (RT) on the vestibulo
      ocular reflex and the effect of "unilateral cold caloric vestibular stimulation"
      on the localization of a RT have previously been proved. As "unilateral caloric
      stimulation" is not a physiological stimulus, the aim of the present study was to
      analyze whether even physiological "bilateral vestibular stimulation" (rotation)
      is able to affect the RT position. The pointing error (PE) towards an RT both
      without and following angular acceleration was investigated in 24 healthy
      volunteers. Postrotatory nystagmus response was recorded by
      electronystagmography. Evaluation parameters were "nystagmus frequency", "total
      amplitude" and "velocity of the slow phase"; the horizontal and vertical PE. The
      fixation of an RT led to a significant reduction of about 28% in nystagmus
      amplitude compared to the test condition in darkness. "After rotatory
      stimulation" a systematic horizontal PE in the direction of the fast phase of the
      postrotatory nystagmus (direction of "illusory self-rotation") occurred and the
      magnitude of this PE increased significantly compared to the test situation
      "without vestibular stimulation", but showed only a non-uniform negative
      correlation with two of the nystagmus parameters. It has to be concluded that
      "after rotatory stimulation", in contrast to "unilateral cold caloric vestibular
      stimulation", the subjective sense of "illusory self-motion" leads to a
      horizontal PE in the direction of the nystagmus fast phases.

PMID- 15951623
TI  - Fluid-structural dynamics of ground-based and microgravity caloric tests.
AB  - Microgravity caloric tests aboard the 1983 SpaceLab1 mission produced nystagmus
      results with an intensity comparable to those elicited during post- and pre-
      flight tests, thus contradicting the basic premise of Barany's convection
      hypothesis for caloric stimulation. In this work, we present a dynamic fluid
      structural analysis of the caloric stimulation of the lateral semicircular canal
      based on two simultaneous driving forces for the endolymphatic flow: natural
      convection driven by the temperature-dependent density variation in the bulk
      fluid and expansive convection caused by direct volumetric displacement of the
      endolymph during the thermal irrigation. Direct numerical simulations indicate
      that on earth, the natural convection mechanism is dominant. But in the
      microgravity environment of orbiting spacecraft, where buoyancy effects are
      mitigated, expansive convection becomes the sole mechanism for producing cupular
      displacement. A series of transient 1 g and microgravity case studies are
      presented to delineate the differences between the dynamics of the 1 g and
      microgravity endolymphatic flows. The impact of these different flow dynamics on
      the endolymph-cupula fluid-structural interactions is also analyzed based on the
      time evolutions of cupular displacement and velocity and the transcupular
      pressure differences.

PMID- 15951624
TI  - The balance control of bilateral peripheral vestibular loss subjects and its
      improvement with auditory prosthetic feedback.
AB  - OBJECTIVES: We investigated whether long-term bilateral vestibular loss subjects
      could combine auditory biofeedback of trunk sway with their remaining natural
      sensory inputs on balance to provide an improved control of trunk sway. A
      successful integration of natural and artificial signals would provide a basis
      for a balance prosthesis. METHODS: Trunk sway of 6 bilateral peripheral
      vestibular loss subjects (BVL) was recorded using either angular position- or
      velocity-based auditory feedback or no feedback during stance and gait tasks.
      Roll and pitch trunk movements were recorded with angular velocity transducers
      mounted just above the waist and feedback without a delay to 4 loudspeakers
      placed at the left, right, front and rear borders of the 5 m long by 4 m wide
      test environment. The two types of auditory feedback or no feedback were provided
      to the subjects in random order. In the feedback modes, sway greater than a
      preset angle (ca. 0.5 deg) or velocity (ca. 3 deg/s) thresholds caused a tone to
      be emitted from the speaker towards which the subject moved. The tone volume
      increased with increasing angle or angular velocity amplitude. RESULTS: For all
      stance tasks BVL subjects without auditory feedback had a significantly different
      balance control with respect to that of normal controls. BVL sway values eyes
      open on a normal surface were reduced with auditory feedback with the greatest
      reductions in the roll plane. Specifically for the task of standing on 1 leg eyes
      open with position-auditory- feedback, amplitudes of pitch and roll angles and
      angular velocities were indistinguishable from those of normal controls. Sway
      during stance tasks on foam with eyes closed showed no improvement with feedback,
      remaining greater than normal. For some gait tasks there was a decrease in trunk
      sway with velocity feedback. CONCLUSION: These initial results indicate that
      subjects with vestibular loss could incorporate the auditory prosthetic sensory
      information into their balance commands, particularly in the roll plane if the
      balance task is performed with eyes open. Position information appears more
      useful than velocity information in reducing trunk sway during stance tasks.
      Future work will need to determine the effect of a training time on the
      improvement in balance control using such a prosthetic device and the ideal
      position and velocity auditory feedback combination.

PMID- 15951625
TI  - Editorial.

PMID- 15951626
TI  - The benefit of combining non-mechanical agents with mechanical loading: a
      perspective based on the Utah Paradigm of Skeletal Physiology.
AB  - The Utah Paradigm of Skeletal Physiology with its key component, the mechanostat
      hypothesis, suggest plausible explanations of some of the tissue-level changes
      occurring from combining selected non-mechanical agents (anabolic and anti
      resorptive/( re)modeling agents) with mechanical loading (osteogenic exercise) to
      increase bone mass and strength. The evidence for combining selected anabolic
      agents like parathyroid hormone, prostaglandin E(2), growth hormone, etc. with
      mechanical loading can increase bone mass is strong. Anabolic agents influence
      loading-related bone formation changes in a permissive manner and modulate
      (increase) the responsiveness of bone tissue to mechanical loading by changing
      thresholds for bone formation and resorption. However, any beneficial effect of
      combining selected anti-resorptive/(re)modeling agents like estrogen with loading
      is marginal, especially in adult skeletons. Postulated changes in modeling and
      remodeling thresholds (set points) and known direct effects on bone cells by non
      mechanical agents may explain the observed tissue-level changes associated with
      large and minor increases in bone mass. Although the pharmaceutical industry has
      avoided considering osteogenic loading in the treatment of osteoporosis, a
      methodical dose-response study of anabolic agents combined with loading should:
      (1) provide opportunities for therapeutic intervention to imitate or enhance the
      osteogenic response to loading in order to correct osteopenias; (2) provide the
      potential to diminish the dosage of drugs required to induce bone formation in
      ways that enhanced efficacy and reduced any side effects; and (3) improve the
      quality of life and reduce the risk of falls by improving balance, gait speed and
      muscle strength with a non-mechanical agent like GH that could improve both
      muscle and bone mass and strength. Lastly, more studies are needed which
      determine bone strength instead of only "mass" in aged skeletons so one can
      assess how effective such treatments would reduce the risk of fracture in the
      clinic.

PMID- 15951627
TI  - Peripheral quantitative computed tomography of the distal radius in young
      subjects - new reference data and interpretation of results.
AB  - Application of bone densitometry to clinical use requires the availability of
      accessible reference data and is helped by an interpretative framework that is
      based on bone physiology. The aim of this contribution is to provide both
      reference data and help in the interpretation of results for peripheral
      quantitative computed tomography (Stratec XCT2000 performed at the distal radius
      of young subjects. Data from a previous reference data study on 478 subjects
      between 6 and 40 years were re-analyzed and smooth curves were fitted. The
      corresponding equations allow for calculation of age- and sex-specific z-scores
      of bone mineral content, volumetric bone mineral density (vBMD) of the trabecular
      compartment, vBMD of the entire radial cross-section, total cross-sectional area
      and cortical thickness. These data should facilitate the clinical use of
      peripheral quantitative computed tomography in young subjects.

PMID- 15951628
TI  - Multifactorial pathogenesis of falls as a basis for multifactorial interventions.

PMID- 15951629
TI  - Prostate cancer cell survival pathways activated by bone metastasis
      microenvironment.
AB  - The development of resistance to anti-cancer therapies in bones is a major hurdle
      preventing long-lasting clinical responses to anti-cancer therapies in hormone
      refractory prostate cancer. Herein, we present the major signal transduction
      pathways, which are activated in prostate cancer cells residing at bone
      metastasis microenvironment. These intracellular signal transduction pathways can
      inhibit anti-cancer therapy-induced apoptosis of metastatic prostate cancer
      cells, thereby optimizing their survival, locally. Employment of this knowledge
      in a clinical setting provides the conceptual framework for the development of
      bone-targeted therapies for advanced prostate cancer. Indeed, bone metastasis
      microenvironment-targeted therapies illustrate a novel paradigm in cancer
      treatment: anti-tumor treatment strategies may not only aim at directly inducing
      cancer cell apoptosis, but can also target the tumor metastasis microenvironment,
      and neutralize the protection it confers on metastatic cancer cells.

PMID- 15951630
TI  - Case-control study of the muscular compartments and osseous strength in
      neurofibromatosis type 1 using peripheral quantitative computed tomography.
AB  - Skeletal anomalies are observed in neurofibromatosis type 1 (NF1), but the
      pathogenesis is unknown. Given that muscle mass is important in the development
      of the strength of bone, peripheral quantitative computed tomography (pQCT) was
      utilized to compare measurements of muscle compartments between NF1 individuals
      and controls. Forty individuals with NF1 (age 5-18 years) were evaluated. Cross
      sectional measurements, at the 66% tibial site, were obtained using pQCT (XCT
      2000, Stratec) and variables were compared to controls without NF1 ((age 5-18
      years, N=380) using analysis-of-covariance controlling for age, height, Tanner
      stage, and gender. The NF1 cohort showed decreased total cross-sectional area
      [p<0.001], decreased muscle plus bone cross-sectional area [p<0.001], decreased
      muscle cross-sectional area [p<0.001], and decreased Stress Strain Index
      [p=0.010]. These data indicate that NF1 individuals have decreased muscle cross
      sectional area and decreased bone strength than individuals without NF1.

PMID- 15951631
TI  - Co-existence of X-linked hypophosphatemic rickets (XLH) and primary
      hyperparathyroidism: case report and review of the literature.
AB  - X-linked hypophosphatemic rickets (XLH) is a dominant disorder characterized by
      hypophosphatemia due to impaired renal tubular reabsorption of inorganic
      phosphate. Cardinal manifestations include defective calcification of cartilage
      and bone, growth retardation and resistance to phosphorus and vitamin D therapy.
      Although secondary hyperparathyroidism (HPT) is a common complication of
      treatment, autonomous HPT is rare, especially in the absence of previous
      phosphate therapy. We report a case of an adult untreated male XLH patient with
      primary HPT and give a brief review of the literature regarding the prevalence
      and pathophysiology of this complication.

PMID- 15951632
TI  - A cybernetic approach to osteoporosis in anorexia nervosa.
AB  - A group of 25 female individuals, who had been admitted to the University
      Hospital with the diagnosis of anorexia nervosa (AN) 3 to 10 years before, was
      seen for a follow-up visit in the hospital. These women got a psychiatric
      exploration to detect a present eating disorder. Moreover, parameters of the
      muskuloskeletal interaction were determined on the non-dominant forearm. Bone
      mineral content (BMC) of the radius was measured by pQCT and maximal grip force
      was evaluated by the use of a dynamometer. Eating disorders were present in 12
      females. The mean of BMC standard deviation (SD) score was significantly reduced
      in comparison with reference values. Furthermore, the mean of BMC SD score was
      also significantly lower than the mean of grip force in SD score. These results
      gave the suggestion that the adaptation of bone mass to biomechanical forces is
      disturbed in AN. The linear regression analyses between the parameters grip force
      and BMC were compared between the study and the reference group. The comparison
      delivered a significantly lower constant in the regression equation of the study
      group. This result can be interpreted on the background of the mechanostat
      theory. The affection with an eating disorder decreases the set point in the
      feedback loop of bone modeling. The results offer for the first time the
      possibility to analyse osteoporosis in anorexic females under the paradigm of
      muskuloskeletal interaction.

PMID- 15951633
TI  - Mechanical assessment of effects of grape seed proanthocyanidins extract on
      tibial bone diaphysis in rats.
AB  - We studied the effects of grape seed proanthocyanidins extract (GSPE) given as a
      ratio of 3 mg in 100 g in a standard diet, on the tibial bone diaphysis in low
      calcium fed rats. Measurements of bone density, mineral content, geometry, and
      bone strength using peripheral quantitative computed tomography (pQCT). Further,
      the whole tibia bones were tested for mechanical resistance using a material
      testing machine, and mineral elements were also determined. Forty male Wistar
      rats, 5 weeks old, were divided into control (Co), low-calcium diet (LC), low
      calcium diet . standard diet (LCS), and low-calcium diet . standard diet with
      supplementary GSPE (LCSG) groups. We found no significant differences in body
      weight among the 4 groups, whereas all of the bone parameters in LC were
      significantly lower than those in Co (p<0.01, except in periosteal perimeter
      (Peri) p<0.05). The cortical bone mineral content (CtBMC), cortical bone density
      (CtvBMD) and Peri in LCSG were significantly higher than those in LCS (p<0.01;
      p<0.01; p<0.05, respectively). All bone parameters in LCSG were significantly
      higher than those in LC (p<0.01, except in Peri, and stress strain index to
      reference axis x (xSSI) p<0.05)). In addition, Ca, P, and Zn contents in LCSG
      were significantly higher than those in LCS (p<0.01; p<0.01; p<0.05,
      respectively). Our results suggest that GSPE included in a diet mixture with
      calcium has a beneficial effect on bone formation and bone strength for the
      treatment of bone debility caused by a low level of calcium.

PMID- 15951634
TI  - The symmetry of the medial collateral and anterior cruciate ligament properties:
      a biochemical study in the rat hind limb.
AB  - The medial collateral (MCL) and the anterior cruciate ligament (ACL) of the rat's
      knee are frequently used in biomedical research and occasionally in ligament
      healing studies. The contralateral normal ligament serves as a control. In this
      study the presence of symmetry in the biomechanical properties of the MCL and the
      ACL was investigated. Bilateral femur-MCL-tibia and femur-ACL-tibia preparations
      were obtained from the hind limbs of sixty rats and were subjected to tensile
      testing to failure under the same loading conditions. Tensile load to failure,
      stiffness and energy absorption capacity were measured and the mode of failure
      was recorded. All biomechanical parameters were not significantly different
      between the two knees of the same animal, although significant individual
      variation was evident. The most common mechanism of failure was mid-substance
      tear. Symmetry seems to exist in the biomechanical properties of the MCL and the
      ACL in the rat knee. When ligament healing is evaluated, increased group size is
      necessary and the use of a normal control group may be advisable. The
      contralateral normal knee ligament may serve as a control when the properties of
      an injured ligament are evaluated and when the parameters of tensile testing
      failure under similar load conditions are applied.

PMID- 15951635
TI  - Changes in bone volume and bone resorption by olpadronate treatment in an
      experimental model of uremic bone disease.
AB  - Thirty male adult Wistar rats (300-/+10 g body weight) underwent either 5/6
      nephrectomy (Nx, n=20) or sham operation (SHAM, n=10) to determine olpadronate
      effects in an experimental model of uremic bone disease. For a 38-day period, 10
      rats received olpadronate (16microg/100g bw) once a week (Nx+OPD) and the other
      vehicle (Nx). SHAM received vehicle. At baseline, treatment onset (t=7 days) and
      end of study (t=45 days) calcium, phosphorus, creatinine, bone alkaline
      phosphatase (b-ALP) and deoxypyridinoline crosslinks (DPyr) were determined. At
      t=0 and t=45 bone mineral density (BMD) was measured by DXA. At t=45 the right
      tibia was removed for bone histology. There were no differences in serum calcium.
      Phosphorus increased in Nx and Nx+OPD compared to SHAM (p<lt 0.05). The b-ALP
      increased from t=0 to t=7 in Nx and Nx+OPD (p<0.05) and decreased thereafter to
      SHAM levels. DPyr/creat increased in Nx compared to SHAM (p<0.05) and Nx+OPD
      (p<0.001). Nx+OPD presented lower DPyr excretion than SHAM rats (p<0.01). At
      t=45, tibia BMD of Nx was 20% and 26% lower than in SHAM (p<0.005) and Nx+OPD,
      respectively, (p<0.001). BMD was higher Nx+OPD than in SHAM (p<0.05). OPD
      prevented the loss of bone volume, the increment in osteoid volume and erosion
      surface observed in Nx group (p<0.05). OPD also prevent the increment in the
      number of osteoclasts (OC) and the active OC surface and decreases the number of
      TRAP(+)-OC (p<0.05). In summary, OLP may be beneficial in osteopenia associated
      to high turnover bone disease of CRF. However, the use of bisphosphonate therapy
      for renal insufficiency must be further investigated in order to clarify
      essential aspects of treatment as the patient selection and several aspects of
      treatment, such as optimum dose, frequency, and safe period of administration.

PMID- 15951637
TI  - 1,25-Dihydroxyvitamin D3 suppresses gene expression of eukaryotic translation
      initiation factor 2 in human promyelocytic leukemia HL-60 cells.
AB  - The physiologically active metabolite of vitamin D(3), 1alpha,25-dihydroxyvitamin
      D(3) (DVD), is a potent inducer of cell differentiation in human myeloid leukemia
      cells. In the present study, we examined changes in gene expression during DVD
      induced cell differentiation of promyelocytic HL-60 cells employing a DNA
      microarray technique. The results identified 7 up-regulated and 9 down-regulated
      genes with a change greater than 1.5-fold after the DVD-treatment for both 2 and
      6 days. Seven of these genes were further examined by reverse transcription
      polymerase chain reaction (RT-PCR). The results showed that findings obtained
      from the DNA microarray analysis and RT-PCR are generally comparable with each
      other. Gene expression of the subunits of eukaryotic translation initiation
      factor 2 was then examined by methods including RT-PCR and real-time PCR. The
      results indicated the suppression of these genes, suggesting a linkage to
      differentiation-associated growth inhibition of these cells.

PMID- 15951638
TI  - The role of domestic tap water in Acanthamoeba contamination in contact lens
      storage cases in Korea.
AB  - A survey was carried out from August to December 2004 in Pusan, Korea to document
      the presence of free-living amoeba (FLA), including the genus Acanthamoeba, in
      both contact lens storage cases and domestic tap water. Acanthamoeba was isolated
      from 5 (4.2%) in 120 contact lens storage cases. Four house tap water samples
      from residents, whose contact lens storage cases had been contaminated by
      Acanthamoeba, were also found to be contaminated with Acanthamoeba. Therefore,
      the contamination rate of FLA and Acanthamoeba in domestic tap water was
      investigated in order to examine the role of domestic tap water in Acanthamoeba
      contamination of contact lens storage cases. FLA and Acanthamoeba were identified
      in 97 (46.8%) and 16 (7.7%) of the 207 domestic tap water samples, respectively.
      There were no significant differences between the contamination rates of FLA in
      tap water according to the filtration plant of origin. No FLA was detected in the
      tap water directly supplied by the water purification plants. Water storage tanks
      appear to promote FLA colonization, including Acanthamoeba, in domestic tap
      water. This increases the risk of Acanthamoeba contamination in contact lens
      storage cases as well as increasing the risk of Acanthamoeba keratitis.

PMID- 15951639
TI  - A case of fatal hyperinfective strongyloidiasis with discovery of autoinfective
      filariform larvae in sputum.
AB  - The autoinfective filariform larva of Strongyloides stercoralis causes
      hyperinfection in immunosuppressed hosts. Here we report on the case of a male
      patient who was admitted to the emergency room at Gwangju Veterans Hospital with
      a complaint of dyspnea, and who was receiving corticosteroid therapy for asthma.
      Many slender larvae of S. stercoralis with a notched tail were detected in
      Papanicolaou stained sputum. They measured 269 +/- 21.2 microm in length and 11
      +/- 0.6 microm in width. The esophagus extended nearly half of the body length.
      The larvae were identified putatively as autoinfective third-stage filariform
      larvae, and their presence was fatal. The autoinfective filariform larva of S.
      stercoralis has not been previously reported in Korea.

PMID- 15951640
TI  - A human infection of Echinostoma hortense in duodenal bulb diagnosed by
      endoscopy.
AB  - As gastroduodenoscopy performed more frequently, case reports of human
      echinostomiasis are increasing in Korea. A Korean woman presented at a local
      clinic with complaints of abdominal pain and discomfort that had persisted for 2
      weeks. Under gastroduodenoscopy, two motile flukes were found attached on the
      duodenal bulb, and retrieved with endoscopic forceps. She had history of eating
      raw frog meat. The two flukes were identified as Echinostoma hortense by egg
      morphology, 27 collar spines with 4 end-group spines, and surface ultrastructural
      characters. This report may prove frogs to be a source of human echinostome
      infections.

PMID- 15951641
TI  - Egg positive rate of Enterobius vermicularis and Taenia spp. by cellophane tape
      method in primary school children in Sivas, Turkey.
AB  - The aim of the present study was to find out the number of students with
      enterobiasis and/or taeniasis in primary schools of Sivas. Among the 2,029
      students in 6 primary schools, 316 (15.6%) were positive to Enterobius
      vermicularis eggs and 32 (1.6%) were positive to Taenia spp. eggs by the
      cellophane tape method. The egg positive rates of E. vermicularis and Taenia spp.
      ranged from 9.4% to 27.2% and from 0.8% to 2.6% respectively among six schools.
      The egg positive rate of E. vermicularis was found to be significantly different
      among these schools (chi2 = 31.96, P < 0.05), whereas there was no significant
      difference between the schools for Taenia spp. (chi2 = 4.37; P > 0.05). The rate
      (18.7%) of E. vermicularis in the urban slum regions was higher than the rate
      (11.5%) in the urban central regions (chi2 = 19.20; P < 0.05). Above results
      demonstrate that the egg positive rate of E. vermicularis and Taenia spp. was
      still prevalent among primary school children.

PMID- 15951642
TI  - Prevalence of Toxocara canis, Toxascaris leonina and Dirofilaria immitis in dogs
      in Chuncheon, Korea (2004).
AB  - The intestines and hearts of dogs were examined for Toxocara canis, Toxascaris
      leonina, and Dirofilaria immitis, after necropsy between June 26 and September
      29, 2004 in Chuncheon, Korea. Of the 662 dogs examined, 6 were infected with T.
      canis (0.9%), 86 with T. leonina (13.0%). Fifty dogs were infected with D.
      immitis among 500 dogs examined (10.0%). Five were co-infected with T. canis and
      T. leonina, and three were co-infected with T. leonina and D. immitis. The
      cumulative positive infection rate for three species was 134/662 (20.2%).
      Considering previously reported seropositive rates of T. canis excretory
      secretory antigen, i.e., 5% in the adult population in Korea, the possibility of
      toxocariasis caused by T. leonina should be reevaluated.

PMID- 15951643
TI  - Seroprevalence of toxoplasmosis in Korean pregnant women.
AB  - This study was performed in order to evaluate the sero-epidemiological status of
      toxoplasmosis in pregnant Korean women. Among 5,175 sera and 750 amniotic fluid
      samples obtained from pregnant women, 41 serum samples (0.79%) and 10 (1.33%)
      amniotic fluid samples tested positive for IgG antibodies by ELISA. Fifty one
      cases showing a score more than 0.25 on ELISA were tested for PCR reaction
      against the SAG1 gene. Only one case of the 51 ELISA positive cases exhibited a
      positive reaction on all tests. This case had a history of acute nephropyelitis
      during early pregnancy, but fortunately, had delivered a phenotypically healthy
      baby. In this study, the seroprevalence of toxoplasmosis in pregnant women was
      found to be comparatively low, consistent with previous reports from Korea.
      However our trials, performed with a variety of diagnostic tools, were considered
      to be useful for the precise diagnosis of congenital toxoplasmosis.

PMID- 15951644
TI  - Reports of memory functioning by patients with chronic pain.
AB  - OBJECTIVES: Patients with chronic pain often complain of memory and concentration
      difficulties. The purpose of this study was to explore the influence of a set of
      variables that previous research has associated with memory complaints in
      patients with chronic pain: anxiety and depression, benzodiazepine use,
      chronicity of pain, and age. Special attention is paid to catastrophizing and to
      the differential role played by its 3 components: magnification, helplessness,
      and rumination. METHODS: The Pain Catastrophizing Scale, the Hospital Anxiety and
      Depression Scale, and the Questionnaire d auto-evaluation de la Memoire were
      administered to 149 patients with benign chronic pain. RESULTS: The most
      frequently reported memory complaints included flaws referring to films and books
      (61%); forgetfulness (44%); handling of everyday things (38%); and flaws about
      conversations (38%). Regression analyses showed that depression accounted for the
      largest proportion of variance in memory complaints (35%) followed by anxiety
      (6%) and rumination (2%). CONCLUSION: The results support the hypothesis that
      emotional distress (depression and anxiety) plays an important role in memory
      complaints in patients with chronic pain, as well as rumination, the intrusive
      component of catastrophizing. Clinicians should be aware of these factors in the
      evaluation of memory complaints in patients with chronic pain.

PMID- 15951645
TI  - Sensitivity of pain rating scales in an endoscopy trial.
AB  - OBJECTIVE: The purpose of this study was to compare the sensitivity of two
      commonly used pain-rating scales, the Visual Analog Scale and the 4-point verbal
      rating scale. Both are considered reliable and valid, but previous studies
      regarding sensitivity of rating scales have lead to different conclusions, and
      there is no firm agreement as to the best scale to choose. METHODS: The
      sensitivity of the Visual Analog Scale and the 4-point verbal rating scale was
      compared by stochastic simulation. In the simulation model, we used 168 pairs of
      pain ratings on the Visual Analog Scale and the 4-point verbal rating scale from
      individuals undergoing a lower gastrointestinal endoscopy, maintaining the true
      relation between ratings from the same individual. We created empirical
      distributions mimicking 2 independent groups of pain ratings. Random samples from
      the 2 groups were compared by the Wilcoxon-Mann-Whitney U test in 10,000
      repetitions of a computer algorithm. By increasing the proportion of individuals
      with a high level of pain in one group, we increased the true difference between
      pain ratings and estimated a statistical power function. RESULTS: In the present
      pain model with pain ratings from healthy individuals undergoing endoscopy, the
      Visual Analog Scale is consistently more sensitive than the four-point verbal
      rating scale. DISCUSSION: Because each individual provided one Visual Analog
      Scale and one 4-point verbal rating scale rating for the same pain experience,
      the ability of the two scales to detect differences between groups of pain
      ratings could be compared. The use of a simulation model enabled estimation of a
      power function and reduced the probability of basing the conclusion on a chance
      finding.

PMID- 15951646
TI  - What do patients expect from their first visit to a pain clinic?
AB  - OBJECTIVE: To examine patients' expectations of their first outpatient visit to a
      pain clinic. We asked patients what would be the most satisfying and the most
      disappointing outcomes of their visit and whether they expected changes in
      medication and further investigations to result from their consultation. DESIGN:
      Patients completed questionnaires and a structured interview to assess
      expectations before their clinic appointment. METHODS: Seventy-seven patients
      with chronic pain who were first time referrals to a regional pain clinic
      participated in the study. Patient expectations and questionnaires measuring
      depression and pain-related disability were completed prior to the pain clinic
      appointment. RESULTS: Most patients expected an explanation or an improved
      understanding of their pain problem. The most common satisfying outcome was
      relief or control of pain, and the most common disappointing outcome was being
      told nothing could be done. The majority of patients expected further medical
      investigations and changes to the prescribed medication. Depression and pain
      related disability strongly influenced patient expectations. CONCLUSIONS: For
      patients attending pain clinics, the explanation of their pain problem is rated
      as important as the cure or relief of their pain. Improved understanding of
      patient expectations by pain clinic clinicians may lead to greater patient
      satisfaction and reduced treatment dropout.

PMID- 15951647
TI  - Patient satisfaction with treatment for chronic pain: predictors and relationship
      to compliance.
AB  - OBJECTIVES: Patient satisfaction with treatment has been extensively researched
      in a variety of medical patients. However, satisfaction with treatment of chronic
      pain has received considerably less attention. The present study sought to
      identify the predictors of patient satisfaction with treatment of chronic pain.
      In addition, the relationship between patient satisfaction and compliance with
      treatment recommendations was explored. METHODS: One hundred eighty patients (84
      men and 96 women) seeking treatment of chronic pain at University of Florida pain
      clinics were recruited for this telephone follow-up study. RESULTS: Satisfaction
      ratings were generally high, with ratings of satisfaction with care significantly
      higher (t179=9.58, P<0.001) than ratings of satisfaction with improvement.
      Aspects of the patient-provider interaction, pain relief, and anxiety at
      treatment onset predicted satisfaction with care. These same variables, with the
      exception of anxiety, also predicted satisfaction with improvement. Those
      patients who were more satisfied with their improvement were also more compliant
      with treatment recommendations, and this relationship was stronger for health
      care provider-rated compliance. DISCUSSION: Results suggest the importance of
      distinguishing between satisfaction with care and satisfaction with improvement
      in assessments. Satisfaction with treatment of chronic pain is not merely a
      matter of pain relief. To increase the probability of treatment success and
      satisfaction, attention to the interpersonal aspects of the health care provider
      patient relationship appear critical. Explanations for satisfaction's stronger
      relationship to health care provider-rated compliance were discussed.

PMID- 15951648
TI  - Studies on the operative outcomes and mechanisms of microvascular decompression
      in treating typical and atypical trigeminal neuralgia.
AB  - OBJECTIVE: To evaluate the operative outcomes and mechanisms of microvascular
      decompression in treating typical and atypical trigeminal neuralgia. METHODS: A
      group of 45 patients with typical trigeminal neuralgia and 17 patients with
      atypical trigeminal neuralgia treated by micro-vascular decompression from 2000
      to 2002 were reviewed, including their clinical presentations, operative
      findings, and outcomes. RESULTS: Of 45 patients with typical trigeminal
      neuralgia, the mean duration was 3.1 years, and the mean age of pain onset was
      60.3 years. Single trigeminal division was involved in 20 patients (44.4%), and 2
      or 3 divisions were involved in the other 25 patients (55.6%). During the
      operation, artery compression was found in 39 patients (86.7%), and the combined
      artery and venous compression was found in 6 patients (13.3%). Postoperatively,
      complete pain relief was achieved in 44 patients (97.8%), and significant pain
      relief was achieved in 1 patient (2.2%). As for 17 patients with atypical
      trigeminal neuralgia, the mean duration and the mean age of pain onset was 8.7
      years and 55.5 years, respectively. Two or 3 trigeminal divisions were involved
      in all of these patients. During operation, artery compression occurred in 10
      patients (58.8%), and the combined artery and venous compression was found in 7
      patients (41.2%). Postoperatively, complete pain relief was achieved in 5
      patients (29.4%), and partial pain relief was achieved in 10 patients (58.8%),
      and 2 patients showed no response to microvascular decompression. CONCLUSIONS:
      The operative outcome of microvascular decompression in patients with typical
      trigeminal neuralgia was better than that of patients with atypical trigeminal
      neuralgia, which perhaps related to short duration, late onset of pain, limited
      distribution, artery compression, and complete operative decompression.

PMID- 15951649
TI  - A prospective cost-effectiveness study of trigeminal neuralgia surgery.
AB  - OBJECTIVES: Approximately 8000 patients with trigeminal neuralgia undergo surgery
      each year in the United States at an estimated cost exceeding $100 million. We
      compared 3 commonly performed surgeries (microvascular decompression, glycerol
      rhizotomy, and stereotactic radiosurgery) to evaluate the relative cost
      effectiveness of these operations for patients with idiopathic trigeminal
      neuralgia. METHODS: Prospective nonrandomized trial at a tertiary referral center
      from July 1999 to December 2001. One hundred twenty-six consecutive patients
      underwent 153 operations (microvascular decompression, n=33; glycerol rhizotomy,
      n=51; stereotactic radiosurgery, n=69). Preoperative characteristics were similar
      between the groups with respect to sex, pain location, duration of pain, and
      atypical features. Facial pain outcomes were classified as excellent (no pain, no
      medications), good (no pain, reduced medications), fair (>50% pain reduction),
      and poor. The cost per quality adjusted pain-free year was compared between the
      groups. Mean follow-up was 20.6 months. RESULTS: Patients having microvascular
      decompression more commonly achieved and maintained an excellent outcome (85% and
      78% at 6 and 24 months) compared with glycerol rhizotomy (61% and 55%, P=0.01)
      and stereotactic radiosurgery (60% and 52%, P<0.01). No difference was detected
      between glycerol rhizotomy and stereotactic radiosurgery (P=0.61). The cost per
      quality adjusted pain-free year was $6,342, $8,174, and $8,269 for glycerol
      rhizotomy, microvascular decompression, and stereotactic radiosurgery,
      respectively. Reduction in the average cost of morbidity and additional surgeries
      to zero did not make either microvascular decompression or stereotactic
      radiosurgery more cost-effective than glycerol rhizotomy. Both microvascular
      decompression and stereotactic radiosurgery would be more cost-effective than
      glycerol rhizotomy if the cost of additional surgeries after glycerol rhizotomy
      increased 79% and 83%, respectively. DISCUSSION: This analysis supports the
      practice of percutaneous surgeries for older patients with medically unresponsive
      trigeminal neuralgia. At longer follow-up intervals, microvascular decompression
      is predicted to be the most cost-effective surgery and should be considered the
      preferred operation for patients if their risk for general anesthesia is
      acceptable. More data are needed to assess the role that radiosurgery should play
      in the management of patients with trigeminal neuralgia.

PMID- 15951650
TI  - Are the changes in postural control associated with low back pain caused by pain
      interference?
AB  - BACKGROUND: Voluntary limb movements are associated with involuntary and
      automatic postural adjustments of the trunk muscles. These postural adjustments
      occur prior to movement and prevent unwanted perturbation of the trunk. In low
      back pain, postural adjustments of the trunk muscles are altered such that the
      deep trunk muscles are consistently delayed and the superficial trunk muscles are
      sometimes augmented. This alteration of postural adjustments may reflect
      disruption of normal postural control imparted by reduced central nervous system
      resources available during pain, so-called "pain interference," or reflect
      adoption of an alternate postural adjustment strategy. METHODS: We aimed to
      clarify this by recording electromyographic activity of the upper (obliquus
      externus) and lower (transversus abdominis/obliquus internus) abdominal muscles
      during voluntary arm movements that were coupled with painful cutaneous
      stimulation at the low back. If the effect of pain on postural adjustments is
      caused by pain interference, it should be greatest at the onset of the stimulus,
      should habituate with repeated exposure, and be absent immediately when the
      threat of pain is removed. Sixteen patients performed 30 forward movements of the
      right arm in response to a visual cue (control). Seventy trials were then
      conducted in which arm movement was coupled with pain ("pain trials") and then a
      further 70 trials were conducted without the pain stimulus ("no pain trials").
      RESULTS: There was a gradual and increasing delay of transversus
      abdominis/obliquus internus electromyograph and augmentation of obliquus externus
      during the pain trials, both of which gradually returned to control values during
      the no pain trials. CONCLUSION: The results suggest that altered postural
      adjustments of the trunk muscles during pain are not caused by pain interference
      but are likely to reflect development and adoption of an alternate postural
      adjustment strategy, which may serve to limit the amplitude and velocity of trunk
      excursion caused by arm movement.

PMID- 15951651
TI  - Local steroid injections for tennis elbow: does the pain get worse before it gets
      better?: Results from a randomized controlled trial.
AB  - OBJECTIVES: To compare the early effects of local corticosteroid injection,
      naproxen, and placebo as treatments for tennis elbow in primary care.
      Specifically, to find out whether the extra pain reduction experienced by
      patients who are given the steroid injection in the short-term would be realized
      within the first 5 days of treatment and to attempt to assess how much extra pain
      may be associated with the injection initially. METHODS: A randomized controlled
      trial carried out in 23 family practices in the United Kingdom. A total of 164
      patients aged 18 to 70 years presenting with a new episode of tennis elbow were
      recruited and invited to keep a daily record of their pain intensity and
      medication use over the first 5 days of randomized treatment using a "diary."
      RESULTS: On day 1, pain scores were higher in the injection group compared with
      the naproxen group and placebo group, and the injection group was also taking
      more painkillers. By day 4, the converse was true, pain scores were significantly
      lower in the injection group than the other 2 groups, and patients given an
      injection were less likely to be taking painkillers than those in the placebo
      group. DISCUSSION: Steroid injection was associated with an increase in reported
      pain for the first 24 hours of treatment, but the therapeutic benefits compared
      with naproxen and placebo were evident 3 to 4 days after the start of treatment.

PMID- 15951652
TI  - Radiofrequency denervation of lumbar facet joints in the treatment of chronic low
      back pain: a randomized, double-blind, sham lesion-controlled trial.
AB  - OBJECTIVES: Radiofrequency facet joint denervation procedures have been common
      practice for 2 decades in treatment of chronic low back pain. We designed this
      multicenter, randomized, double-blind, sham treatment controlled trial to
      determine the efficacy of radiofrequency facet joint denervation, as it is
      routinely performed. METHODS: Inclusion criteria were low back pain, duration
      more than 6 months, and >or=50% Visual Analog Scale (VAS) reduction on diagnostic
      block. Exclusion criteria were prior radiofrequency treatment, radicular
      syndrome, coagulopathies, specific allergies, cancer, and pregnancy. A total of
      81 out of 462 patients were randomized to undergo radiofrequency facet joint
      denervation or sham treatment. The first evaluation was carried out 3 months
      after treatment. Primary outcome was determined with a combined outcome measure
      comprising VAS, physical activities, and analgesic intake, from a twice-weekly
      recorded diary. Secondary outcome measures were the separate diary parameters,
      global perceived effect (complete relief, >50% relief, no effect, pain increase),
      and SF-36 Quality of Life Questionnaire. RESULTS: There were no dropouts before
      the first evaluation. The combined outcome measure showed no differences between
      radio- frequency facet joint denervation (n=40; success 27.5%) and sham (n=41;
      success 29.3%) (P=0.86). The VAS in both groups improved (P<0.001). Global
      perceived effect improved after radiofrequency facet joint denervation (P<0.05).
      The other secondary outcome parameters showed no significant differences.
      Relevant costs were evaluated. DISCUSSION: The combined outcome measure and VAS
      showed no difference between radiofrequency and sham, though in both groups,
      significant VAS improvement occurred. The global perceived effect was in favor of
      radiofrequency. In selected patients, radiofrequency facet joint denervation
      appears to be more effective than sham treatment.

PMID- 15951653
TI  - The effect of opioids on driving and psychomotor performance in patients with
      chronic pain.
AB  - OBJECTIVES: This study compared the psychomotor performance and driving ability
      of patients with chronic pain managed with stable regimens of opioid analgesics
      with that of normal healthy volunteers. The hypothesis was that patients with
      chronic pain on stable opioid analgesic regimens operate their automobiles safely
      with proficiency equal to normal volunteer controls. METHODS: Patients were
      evaluated for errors while driving their own automobile through a predetermined
      route in the community, including variable residential and highway conditions,
      and for speed and accuracy on repeated trials through a 5-station obstacle course
      that evaluated forward and reverse driving, turning, and parallel parking.
      Patients also completed the Test of Variables of Attention and the Digit Symbol
      Substitution Test. RESULTS: No significant differences were observed among groups
      in driving performance in the community and on the obstacle course or on the Test
      of Variables of Attention. Results on dependent measures within the opioid group
      generally were not correlated with morphine equivalent daily opioid doses, which
      averaged 118 mg (median 40 mg). CONCLUSIONS: Many patients with chronic pain,
      even if treated with potent analgesics such as morphine and hydromorphone, show
      comparable driving ability as normals.

PMID- 15951654
TI  - Is temporomandibular pain in chronic whiplash-associated disorders part of a more
      widespread pain syndrome?
AB  - OBJECTIVES: The prevalence of temporomandibular disorders in patients with
      chronic whiplash-associated disorder is a controversial issue that may be
      influenced by the widespread pain character and psychologic distress frequently
      observed in patients with chronic pain. The aim of this study was to determine
      the prevalence of temporomandibular disorder pain, widespread pain, and
      psychologic distress in persons with chronic whiplash-associated disorder pain,
      using a controlled, single blind study design. The prevalence of
      temporomandibular disorder pain in the chronic whiplash-associated disorder pain
      group was compared with 2 control groups: a chronic neck pain group and a no neck
      pain group. METHODS: From 65 persons, a standardized oral history was taken, a
      physical examination of the neck and the masticatory system was performed,
      widespread pain was investigated by tender point palpation, and psychologic
      distress was measured with a questionnaire (SCL-90). Because the recognition of
      temporomandibular disorder pain and neck pain remains a matter of debate, 3 well
      defined classification systems were used: one based on the oral history, a second
      on a combination of oral history and pain on active movements and palpation, and
      a third one based on a combination of oral history and function tests. RESULTS:
      Irrespective of the classification system used, the chronic whiplash-associated
      disorder pain group more often suffered from temporomandibular disorder pain
      (0.001<P<0.028) and widespread pain (0.001<P<0.003) than the no neck pain group.
      Moreover, patients with whiplash-associated disorder showed more psychologic
      distress (0.000<P<0.044) than the other 2 groups. DISCUSSION: The higher
      prevalence of widespread pain and psychologic distress in patients with chronic
      whiplash-associated disorder suggests that the higher prevalence of
      temporomandibular disorder pain in these patients is part of a more widespread
      chronic pain disorder.

PMID- 15951655
TI  - Tiagabine and gabapentin for the management of chronic pain.
AB  - OBJECTIVE: Agents that modulate gamma-aminobutyric acid transmission, such as
      gabapentin, are widely used for the management of chronic pain
      disorders/syndromes; however, the usefulness of the selective gamma-aminobutyric
      acid reuptake inhibitor tiagabine in this therapeutic area has yet to be
      investigated. This study evaluated the effectiveness and safety of tiagabine and
      gabapentin for the treatment of chronic pain. METHODS: This 3-month, open-label,
      comparative study randomized 91 patients with chronic pain to receive either
      tiagabine (maximum dose 24 mg/day) or gabapentin (2400 mg/day). Patients rated
      their pain intensity and sleep quality using 11-point (0-10) scales prior to
      treatment and after 3 months of continuous treatment. RESULTS: Of the 46 patients
      receiving tiagabine, 36 (78%) completed the study; 38 of 45 patients (84%)
      receiving gabapentin completed the study. Tiagabine and gabapentin significantly
      reduced pain intensity and improved sleep quality at 3 months, compared with
      baseline (P<0.01). Improvements in sleep quality were significantly greater in
      tiagabine versus gabapentin-treated patients (P=0.04). CONCLUSIONS: These results
      suggest that tiagabine and gabapentin are effective in the management of chronic
      pain, with tiagabine having a greater beneficial effect on sleep quality.

PMID- 15951656
TI  - Painful hallucinations and somatic delusions in a patient with the possible
      diagnosis of neuroborreliosis.
AB  - Neuroborreliosis has become the most frequently recognized tick-borne infection
      of the nervous system in Europe and the United States. In addition to
      dermatological, cardiac, articular, and neurologic manifestations, psychiatric
      disorders such as depression, panic attacks, and schizophrenia-like psychosis can
      also arise. We report on a 61-year-old woman who developed a severe pain syndrome
      following several tick bites. She was diagnosed with neuroborreliosis; she
      received various courses of antibiotics over several years, but without any
      clinical improvement in her condition. Her eventual admission to a psychiatric
      ward due to mental symptoms and neuroleptic treatment led to a dramatic
      improvement of her pain symptoms. However, increasing delusions disclosed a
      psychotic episode, which ceased over time. We discuss therapeutic difficulties
      and psychiatric complications in the absence of a clear-cut diagnosis of
      neuroborreliosis. Although this patient might have suffered from late-onset
      schizophrenia with painful hallucinations right from the start of her disease,
      the case highlights psychiatric complications that might be associated with
      neuroborreliosis.

PMID- 15951657
TI  - Management of chronic neuropathic pain with methadone: a review of 13 cases.
AB  - The synthetic opioid methadone has generated much interest in recent years among
      clinicians involved in the management of intractable chronic cancer pain. Its use
      as an analgesic is starting to extend to the treatment of noncancer pain,
      particularly neuropathic pain. Unfortunately, the evidence for its use in the
      management of neuropathic pain is limited to a few case studies. We examined
      retrospectively during a 12-month study period the clinical response of all 13
      patients at our pain clinic who were prescribed methadone in an attempt to
      control neuropathic pain resistant to conventional analgesics. A questionnaire
      was also administered to the 9 patients who continued to take methadone at 12
      months posttreatment. A total of 4 patients (31%) discontinued it by the end of
      the 12-month study period. Patients discontinued methadone due to the absence of
      pain relief and due to various intractable, undesirable side effects. Somnolence
      was the most common adverse effect reported, followed by nausea, constipation,
      and vomiting. All patients took coanalgesics (eg, amitriptyline, gabapentin) or
      other analgesics (eg, morphine, nonsteroidal anti-inflammatory drugs) during
      methadone treatment to control pain. The 9 patients who continued to take
      methadone at 12 months reported experiencing on average 43% pain relief (range 0
      80%), 47% improvement in quality of life (range 0-100%), and 30% improvement in
      quality of sleep (range 0-60%). Methadone was effective at relieving pain and
      ameliorating quality of life and sleep in 62% of patients. These findings suggest
      that methadone can offer an acceptable success rate for the treatment of
      neuropathic pain. Prospective randomized, placebo-controlled studies are now
      needed to examine more rigorously the benefits of methadone for this type of
      pain.

PMID- 15951658
TI  - On health effects of ozone exposure and exposing the epidemiologic process.

PMID- 15951659
TI  - Ambient ozone and mortality.

PMID- 15951660
TI  - The methodologic ozone effect.

PMID- 15951661
TI  - A meta-analysis of time-series studies of ozone and mortality with comparison to
      the national morbidity, mortality, and air pollution study.
AB  - BACKGROUND: Although many time-series studies of ozone and mortality have
      identified positive associations, others have yielded null or inconclusive
      results, making the results of these studies difficult to interpret. METHODS: We
      performed a meta-analysis of 144 effect estimates from 39 time-series studies,
      and estimated pooled effects by lags, age groups, cause-specific mortality, and
      concentration metrics. We compared results with pooled estimates from the
      National Morbidity, Mortality, and Air Pollution Study (NMMAPS), a time-series
      study of 95 large U.S. urban centers from 1987 to 2000. RESULTS: Both meta
      analysis and NMMAPS results provided strong evidence of a short-term association
      between ozone and mortality, with larger effects for cardiovascular and
      respiratory mortality, the elderly, and current-day ozone exposure. In both
      analyses, results were insensitive to adjustment for particulate matter and model
      specifications. In the meta-analysis, a 10-ppb increase in daily ozone at single
      day or 2-day average of lags 0, 1, or 2 days was associated with an 0.87%
      increase in total mortality (95% posterior interval = 0.55% to 1.18%), whereas
      the lag 0 NMMAPS estimate is 0.25% (0.12% to 0.39%). Several findings indicate
      possible publication bias: meta-analysis results were consistently larger than
      those from NMMAPS; meta-analysis pooled estimates at lags 0 or 1 were larger when
      only a single lag was reported than when estimates for multiple lags were
      reported; and heterogeneity of city-specific estimates in the meta-analysis were
      larger than with NMMAPS. CONCLUSIONS: This study provides evidence of short-term
      associations between ozone and mortality as well as evidence of publication bias.

PMID- 15951662
TI  - Associations between ozone and daily mortality: analysis and meta-analysis.
AB  - BACKGROUND: There is ample evidence that short-term ozone exposure is associated
      with transient decrements in lung functions and increased respiratory symptoms,
      but the short-term mortality effect of such exposures has not been established.
      METHODS: We conducted a review and meta-analysis of short-term ozone mortality
      studies, identified unresolved issues, and conducted an additional time-series
      analysis for 7 U.S. cities (Chicago, Detroit, Houston, Minneapolis-St. Paul, New
      York City, Philadelphia, and St. Louis). RESULTS: Our review found a combined
      estimate of 0.39% (95% confidence interval = 0.26-0.51%) per 10-ppb increase in 1
      hour daily maximum ozone for the all-age nonaccidental cause/single pollutant
      model (43 studies). Adjusting for the funnel plot asymmetry resulted in a
      slightly reduced estimate (0.35%; 0.23-0.47%). In a subset for which particulate
      matter (PM) data were available (15 studies), the corresponding estimates were
      0.40% (0.27-0.53%) for ozone alone and 0.37% (0.20-0.54%) with PM in model. The
      estimates for warm seasons were generally larger than those for cold seasons. Our
      additional time-series analysis found that including PM in the model did not
      substantially reduce the ozone risk estimates. However, the difference in the
      weather adjustment model could result in a 2-fold difference in risk estimates
      (eg, 0.24% to 0.49% in multicity combined estimates across alternative weather
      models for the ozone-only all-year case). CONCLUSIONS: Overall, the results
      suggest short-term associations between ozone and daily mortality in the majority
      of the cities, although the estimates appear to be heterogeneous across cities.

PMID- 15951663
TI  - Ozone exposure and mortality: an empiric bayes metaregression analysis.
AB  - BACKGROUND: Results from time-series epidemiologic studies evaluating the
      relationship between ambient ozone concentrations and premature mortality vary in
      their conclusions about the magnitude of this relationship, if any, making it
      difficult to estimate public health benefits of air pollution control measures.
      We conducted an empiric Bayes metaregression to estimate the ozone effect on
      mortality, and to assess whether this effect varies as a function of hypothesized
      confounders or effect modifiers. METHODS: We gathered 71 time-series studies
      relating ozone to all-cause mortality, and we selected 48 estimates from 28
      studies for the metaregression. Metaregression covariates included the
      relationship between ozone concentrations and concentrations of other air
      pollutants, proxies for personal exposure-ambient concentration relationships,
      and the statistical methods used in the studies. For our metaregression, we
      applied a hierarchical linear model with known level-1 variances. RESULTS: We
      estimated a grand mean of a 0.21% increase (95% confidence interval = 0.16-0.26%)
      in mortality per 10-microg/m increase of 1-hour maximum ozone (0.41% increase per
      10 ppb) without controlling for other air pollutants. In the metaregression, air
      conditioning prevalence and lag time were the strongest predictors of between
      study variability. Air pollution covariates yielded inconsistent findings in
      regression models, although correlation analyses indicated a potential influence
      of summertime PM2.5. CONCLUSIONS: These findings, coupled with a greater relative
      risk of ozone in the summer versus the winter, demonstrate that geographic and
      seasonal heterogeneity in ozone relative risk should be anticipated, but that the
      observed relationship between ozone and mortality should be considered for future
      regulatory impact analyses.

PMID- 15951664
TI  - Risk of spontaneous preterm birth is associated with common proinflammatory
      cytokine polymorphisms.
AB  - BACKGROUND: Preliminary data suggest that common genetic variation in immune
      response genes can contribute to the risk for spontaneous preterm birth and
      possibly small-for-gestational age (SGA). METHODS: We investigated the
      relationship of polymorphisms in 6 cytokine genes associated with inflammation
      interleukin (IL)1alpha, IL1beta, IL2, IL6, tumor necrosis factor (TNF), and
      lymphotoxin alpha (LTA)-with spontaneous preterm and SGA birth in a nested case
      control study drawn from a prospective pregnancy cohort. Women were recruited
      between 24 and 29 weeks' gestation at the Wake County and University of North
      Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We
      inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. We
      then compared haplotype frequency distributions and implemented semi-Bayesian
      hierarchical logistic regression analyses to obtain odds ratio (OR) estimates and
      95% confidence intervals (CIs) for each polymorphism. RESULTS: Two haplotypes
      spanning the TNF/LTA genes were associated with increased risk for spontaneous
      preterm birth in white subjects (for the AGG haplotype, OR = 1.5 [95% CI=0.8
      2.6]; for the GAC haplotype, 1.6 [0.9-2.9]). Additionally, carriers of the GAG
      haplotype were found to have decreased risk of spontaneous preterm birth (0.6;
      0.3-1.0). The TNF(-488)A and LTA(IVS1-82)C variants, constituents of the AGG and
      GAC haplotypes respectively, were also strongly associated with increased risk of
      spontaneous preterm birth. CONCLUSIONS: Our results suggest that common genetic
      variants in proinflammatory cytokine genes could influence the risk for
      spontaneous preterm birth. Selected TNF/LTA haplotypes were associated with
      spontaneous preterm birth in both African-American and white subjects. Our data
      do not support an inflammatory etiology for SGA.

PMID- 15951665
TI  - Risk of small-for-gestational age is associated with common anti-inflammatory
      cytokine polymorphisms.
AB  - BACKGROUND: Anti-inflammatory cytokines play a key role in pregnancy maintenance.
      Genetic variation in anti-inflammatory cytokines could influence a woman's risk
      of adverse reproductive outcomes. METHODS: We investigated the relationship of
      polymorphisms in interleukin 4 (IL4), IL5, IL10, IL13, and transforming growth
      factor (TGFbeta1) with spontaneous preterm birth and small-for-gestational age
      (SGA) in a nested case-control study of a prospective pregnancy cohort. Women
      were recruited between 24 and 29 weeks' gestation at the Wake County and
      University of North Carolina, Chapel Hill obstetric clinics between February 1996
      and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian
      method, PHASE. Semi-Bayesian hierarchical logistic regression was used to obtain
      odds ratio (OR) estimates and 95% confidence intervals (CIs) for each
      polymorphism. RESULTS: African-American mothers who carried the IL4 GCC haplotype
      had greater risk of spontaneous preterm birth (OR = 2.9; 95% CI = 1.2-7.4). In
      white mothers, carriers of the "low-producing" IL4 CC and IL10 ATA haplotypes had
      markedly reduced risk of SGA (for the CC haplotype, 0.2 [0.0-1.2]; for the ATA
      haplotype, 0.5 [0.3-0.8]), whereas carriers of the "high-producing" IL4(-589)T
      variant had increased risk of SGA in both African-American and white mothers.
      CONCLUSIONS: Variants related to decreased anti-inflammatory cytokine production
      may lower risk of SGA. Furthermore, the same mechanism that protects against SGA
      might increase risk of spontaneous preterm birth.

PMID- 15951666
TI  - Urinary phthalate metabolites and biomarkers of reproductive function in young
      men.
AB  - BACKGROUND: High exposure to phthalates, which are ubiquitous contaminants, has
      been shown in animal studies to produce detrimental effects on male reproductive
      functions. A recent study in humans reported dose-response relations between low
      phthalate levels in urine and human semen parameters, which raises the question
      whether humans are more sensitive to phthalate exposure than animals. METHODS:
      Urine, serum, and semen samples were collected from 234 young Swedish men at the
      time of their medical conscript examination. Semen volume, sperm concentration,
      and motility were measured, together with sperm chromatin integrity (sperm
      chromatin structure assay) and biochemical markers of epididymal and prostatic
      function. We analyzed reproductive hormones in serum, and mono ethyl phthalate
      (MEP), mono ethylhexyl phthaltale (MEHP), mono benzyl phthalate (MBzP), mono
      butyl phthalate (MBP), and phthalic acid in urine. RESULTS: For MBP, MBzP, and
      MEHP, no clear pattern of associations were observed with any of the reproductive
      biomarkers. Subjects within the highest quartile for MEP had fewer motile sperm
      (mean difference = 8.8%; 95% confidence interval = 0.8-17), more immotile sperms
      (8.9%; 0.3-18), and lower luteinizing hormone values (0.7 IU/L; 0.1-1.2), but
      there was no suggestion of harmful effects for most other endpoints. Phthalic
      acid actually was associated with improved function, as measured by several
      markers. CONCLUSIONS: The observed weak associations between 1 phthalate
      biomarker and impairment of a few aspects of reproductive function biomarkers
      were not consistent with results from a recent U.S. study. It is not yet possible
      to conclude whether phthalate exposure may reflect a hazard for human male
      reproduction.

PMID- 15951667
TI  - Has human fertility declined over time?: why we may never know.
AB  - BACKGROUND: Reports of decreased semen quality over time have raised concerns
      about possible reductions in human fertility. Studies of couple fertility have
      produced conflicting results. We evaluate how changes in the availability and use
      of effective contraception and induced abortion might bias the direct study of
      time trends in couple fertility. METHODS: We assess the potential for bias in the
      context of 2 common study designs: (1) a study of time-to-pregnancy that
      estimates fecundability (excluding unintended pregnancies) and (2) a study of
      infertility rates that categorizes couples as fertile or infertile (including
      couples with unintended pregnancies as fertile). RESULTS: In time-to-pregnancy
      studies, bias alone could produce more than a 2-fold apparent increase in
      fecundability over recent decades. In studies of infertility rates, the bias
      works in the opposite direction: a 30% underestimation of infertility during
      earlier decades could produce an apparent decrease in fertility over time.
      CONCLUSIONS: Over the past 5 decades, changes in social factors that affect the
      rate and fate of unintended pregnancies could substantially bias time trends in
      fertility. These biases may explain the conflicting reports in the literature.
      Except in rare settings in which the factors affecting reproductive choices have
      not changed, it is probably impossible to identify biologic changes in fertility
      over recent decades.

PMID- 15951668
TI  - Causes of infertility as predictors of subsequent cancer risk.
AB  - BACKGROUND: Although studies have found elevated risks of certain cancers linked
      to infertility, the underlying reasons remain unclear. METHODS: In a
      retrospective cohort study of 12,193 U.S. women evaluated for infertility between
      1965 and 1988, 581 cases of cancer were identified through 1999. We used
      standardized incidence ratios (SIRs) to compare cancer risk with the general
      population. Analyses within the cohort estimated rate ratios (RRs) associated
      with infertility after adjusting for other risk predictors. RESULTS: Infertility
      patients demonstrated a higher cancer risk than the general population (SIR =
      1.23; 95% confidence interval [CI] = 1.1-1.3), with nulligravid (primary
      infertility) patients at even higher risk (1.43; 1.3-1.6). Particularly elevated
      risks among primary infertility patients were observed for cancers of the uterus
      (1.93) and ovaries (2.73). Analyses within the cohort revealed increased RRs of
      colon, ovarian, and thyroid cancers, and of melanomas associated with
      endometriosis. Melanomas were linked with anovulatory problems, whereas uterine
      cancers predominated among patients with tubal disorders. When primary
      infertility patients with specific causes of infertility were compared with
      unaffected patients who had secondary infertility, endometriosis was linked with
      distinctive excesses of cancers of the colon (RR = 2.40; 95% CI = 0.7-8.4),
      ovaries (2.88; 1.2-7.1), and thyroid (4.65; 0.8-25.6) cancers, as well as
      melanomas (2.32; 0.8-6.7). Primary infertility due to anovulation particularly
      predisposed to uterine cancer (2.42; 1.0-5.8), and tubal disorders to ovarian
      cancer (1.61; 0.7-3.8). Primary infertility associated with male-factor problems
      was associated with unexpected increases in colon (2.85; 0.9-9.5) and uterine
      (3.15; 1.0-9.5) cancers. CONCLUSIONS: The effects of infertility may extend
      beyond gynecologic cancers. Thyroid cancers and melanomas deserve specific
      attention, particularly with respect to endometriosis.

PMID- 15951670
TI  - Organochlorines in carpet dust and non-Hodgkin lymphoma.
AB  - BACKGROUND: The incidence of non-Hodgkin lymphoma (NHL) has risen over the past
      several decades. Reasons for this increase are largely unexplained. METHODS: In
      this population-based case-control study, we examined NHL risk and exposure to
      organochlorine compounds using concentrations in carpet dust as an exposure
      indicator. We identified NHL cases, uninfected with HIV, diagnosed between 1998
      and 2000 among women and men ages 20-74 years in Iowa, Los Angeles County, and
      the Detroit and Seattle metropolitan areas. Controls were selected using random
      digit-dialing or Medicare files. Organochlorine concentrations were measured in
      vacuum bag dust from 603 white cases and 443 white controls who had owned most of
      their carpets for at least 5 years. RESULTS: NHL risk was elevated if any of the
      polychlorinated biphenyl (PCB) congeners (PCBs 105, 138, 153, 170, or 180) was
      detected (odds ratio = 1.5; 95% confidence interval = 1.2-2.0). Risk was elevated
      in the top tertile of PCB 180 (1.7; 1.1-2.6) and in the top 2 tertiles of total
      PCBs (middle tertile, 1.6 [1.1-2.4]; top tertile 1.5 [1.0-2.2]). There was a
      positive trend in risk with increasing PCB 180 levels (P trend = 0.03). NHL risk
      was elevated if dichlorodiphenyldichloroethylene (DDE) was detected (1.3; 1.0
      1.7), but only among men. A positive, but not monotonic, dose-response
      relationship was observed for DDE (P trend = 0.02). CONCLUSIONS: Our findings
      suggest an increased risk of NHL associated with exposure to PCBs, with evidence
      of greater effects for PCB 180. There is also some evidence of an association
      with DDE.

PMID- 15951669
TI  - Mathematical models of ovarian cancer incidence.
AB  - BACKGROUND: Pike has proposed "protected time" as one summary method for modeling
      reproductive risk factors in relation to ovarian cancer incidence. We evaluate
      this and other approaches to summarizing risk for ovarian cancer. METHODS: We
      identified 472 incident cases of ovarian cancer during 2,298,068 person-years of
      follow-up of 24- to 55-year-old premenopausal women at cohort inception.
      Reproductive exposures, use of oral contraceptives, and history of tubal ligation
      were evaluated. RESULTS: Age at menopause is directly related to cumulative risk
      of ovarian cancer up to age 70 years (age 55 vs. age 45, risk increase = 62%; 95%
      confidence interval = 36 to 96%) and age at menarche is inversely related to risk
      (age 15 vs. 11, risk reduction = 31%; 27-34%). Use of oral contraceptives for 5
      years before age 30 decreases risk of ovarian cancer to age 70 by 37% (32 to
      41%). Tubal ligation reduces risk up to age 70 by 21% (-2 to 38%). Parity reduces
      risk, independent of age at first birth and age at last birth. A model
      summarizing years of ovulation offers a fit comparable to a more complex modeling
      of reproductive variables. The model fit is good, with a concordance statistic of
      0.60 (0.57 to 0.62) indicating reasonable ability to differentiate those who will
      develop ovarian cancer from those who will remain disease free. CONCLUSION: This
      model may be applied in the identification of women at high risk for ovarian
      cancer, for example, in selecting candidates for prevention trials.

PMID- 15951671
TI  - Childhood leukemia and socioeconomic status in Canada.
AB  - BACKGROUND: Leukemia is one of the most common potentially fatal illnesses in
      children, and its causes are not well understood. Although socioeconomic status
      (SES) has been related to leukemia in some studies, this apparent association may
      be attributable to ascertainment or participation bias. This study was undertaken
      to determine whether there is a difference in incidence of childhood leukemia for
      different levels of SES, as measured by neighborhood income, in an unselected
      population case group. METHODS: All cases of childhood leukemia diagnosed in the
      years 1985-2001 were identified from population-based cancer registries in
      Canada. Postal codes for the place of residence at diagnosis were used to
      ascertain the census neighborhoods for cases. We constructed neighborhood-based
      income quintiles from census population data, and stratified the population at
      risk by sex and 5-year age groupings. Age-standardized incidence rates and 95%
      confidence intervals (CIs) were calculated. We used Poisson regression to compare
      incidence rate ratios (RRs) across income quintiles. RESULTS: A slightly lower
      relative risk of childhood leukemia was observed in the poorest quintile compared
      with the richest (RR = 0.87; 95% CI = 0.80-0.95). The lower risk in the poorest
      quintile was restricted to acute lymphoid leukemia (0.86; 0.78-0.95) and was
      strengthened slightly by restriction to urban areas (0.83; 0.74-0.93).
      CONCLUSIONS: This analysis suggests that high SES is a true risk factor for
      childhood leukemia and that inconsistent results from other studies may be
      related to differences in case ascertainment or study participation.

PMID- 15951672
TI  - Residual spatial correlation between geographically referenced observations: a
      Bayesian hierarchical modeling approach.
AB  - BACKGROUND: Analytic methods commonly used in epidemiology do not account for
      spatial correlation between observations. In regression analyses, this omission
      can bias parameter estimates and yield incorrect standard error estimates. We
      present a Bayesian hierarchical model (BHM) approach that accounts for spatial
      correlation, and illustrate its strengths and weaknesses by applying this
      modeling approach to data on Wuchereria bancrofti infection in Haiti. METHODS: A
      program to eliminate lymphatic filariasis in Haiti assessed prevalence of W.
      bancrofti infection in 57 schools across Leogane Commune. We analyzed the spatial
      pattern in the prevalence data using semi-variograms and correlograms. We then
      modeled the data using (1) standard logistic regression (GLM); (2) non-Bayesian
      logistic generalized linear mixed models (GLMMs) with school-specific nonspatial
      random effects; (3) BHMs with school-specific nonspatial random effects; and (4)
      BHMs with spatial random effects. RESULTS: An exponential semi-variogram with an
      effective range of 2.15 km best fit the data. GLMM and nonspatial BHM point
      estimates were comparable and also were generally similar with the marginal GLM
      point estimates. In contrast, compared with the nonspatial mixed model results,
      spatial BHM point estimates were markedly attenuated. DISCUSSION: The clear
      spatial pattern evident in the Haitian W. bancrofti prevalence data and the
      observation that point estimates and standard errors differed depending on the
      modeling approach indicate that it is important to account for residual spatial
      correlation in analyses of W. bancrofti infection data. Bayesian hierarchical
      models provide a flexible, readily implementable approach to modeling spatially
      correlated data. However, our results also illustrate that spatial smoothing must
      be applied with care.

PMID- 15951673
TI  - Positional accuracy of two methods of geocoding.
AB  - BACKGROUND: Geocoding is often used in epidemiologic studies to map residences
      with geographic information systems (GIS). The accuracy of the method is usually
      not determined. METHODS: We collected global positioning system (GPS)
      measurements at homes in a case-control study of non-Hodgkin lymphoma in Iowa. We
      geocoded the addresses by 2 methods: (1) in-house, using ArcView 3.2 software and
      the U.S. Census Bureau TIGER 2000 street database; and (2) automated geocoding by
      a commercial firm. We calculated the distance between the geocoded and GPS
      location (positional error) overall and separately for homes within towns and
      outside (rural). We evaluated the error in classifying homes with respect to
      their proximity to crop fields. RESULTS: Overall, the majority of homes were
      geocoded with positional errors of less than 100 m by both methods (ArcView/TIGER
      2000, median = 62 m [interquartile range = 39-103]; commercial firm, median = 61
      m [interquartile range = 35-137]). For town residences, the percent geocoded with
      errors of </=100 m was 81% for ArcView/TIGER 2000 and 84% for the commercial
      firm. For rural residences, a smaller percent of addresses were geocoded with
      this level of accuracy, especially by the commercial firm (ArcView/TIGER 2000,
      56%; commercial firm, 28%). Geocoding errors affected our classification of homes
      according to their proximity to agricultural fields at 100 m, but not at greater
      distances (250-500 m). CONCLUSIONS: Our results indicate greater positional
      errors for rural addresses compared with town addresses. Using a commercial firm
      did not improve accuracy compared with our in-house method. The effect of
      geocoding errors on exposure classification will depend on the spatial variation
      of the exposure being studied.

PMID- 15951674
TI  - Bounding causal effects under uncontrolled confounding using counterfactuals.
AB  - Common sensitivity analysis methods for unmeasured confounders provide a
      corrected point estimate of causal effect for each specified set of unknown
      parameter values. This article reviews alternative methods for generating
      deterministic nonparametric bounds on the magnitude of the causal effect using
      linear programming methods and potential outcomes models. The bounds are
      generated using only the observed table. We then demonstrate how these bound
      widths may be reduced through assumptions regarding the potential outcomes under
      various exposure regimens. We illustrate this linear programming approach using
      data from the Cooperative Cardiovascular Project. These bounds on causal effect
      under uncontrolled confounding complement standard sensitivity analyses by
      providing a range within which the causal effect must lie given the validity of
      the assumptions.

PMID- 15951675
TI  - Age at menopause, cause-specific mortality and total life expectancy.
AB  - BACKGROUND: A later menopause has been associated with a decreased cardiovascular
      risk but with an increased risk for breast and endometrial cancer. The net effect
      on mortality is unclear. We determined the association of age at menopause with
      longevity and with the balance between cardiovascular and cancer mortality.
      METHODS: We analyzed data from a breast cancer screening cohort comprising 12,134
      postmenopausal women followed for an average of 17 years. We used Cox
      proportional hazards models and life tables to calculate the life expectancy of
      an average Dutch woman at age 50. RESULTS: During 204,024 person-years, there
      were 2607 deaths, of which 963 were due to cardiovascular diseases and 812 due to
      cancer. Ischemic heart disease risk decreased with a later menopause (hazard
      ratio [HR] = 0.98 per year; 95% confidence interval = 0.96-0.99), but the risk of
      fatal uterine or ovarian cancer increased (1.07 per year; 1.01-1.12). A later
      menopause was associated with longer overall survival; HR for total mortality was
      0.98 per year (0.97-0.99). Life expectancy in women with menopause after age 55
      was 2.0 years longer than those with menopause before age 40. Adjustment for
      potential confounders did not materially change the results. CONCLUSIONS: Age
      adjusted mortality is reduced 2% with each increasing year of age at menopause.
      In particular, ischemic heart disease mortality is 2% lower. Although the risk of
      death from uterine or ovarian cancer is increased by 5%, the net effect of a
      later menopause is an increased lifespan.

PMID- 15951676
TI  - Birth weight of offspring and subsequent cardiovascular mortality of the parents.
AB  - BACKGROUND: Restricted fetal growth has been associated with increased blood
      pressure, insulin resistance, and cardiovascular disease in later life. These
      associations may be due to processes during fetal development with long-term
      consequences for metabolic and cardiovascular function (the fetal origins
      hypothesis). However, it has also been hypothesized that common genetic factors
      could underlie both restricted fetal development and disease risk (the fetal
      insulin hypothesis). METHODS: We have investigated associations between offspring
      size at birth and parental mortality in a record linkage study including all
      783,814 children born in Sweden between 1973 and 1980. The deaths of 10,368
      mothers and 22,807 fathers had been recorded by date and causes of death. Data
      were analyzed using Cox proportional hazards regression models, with parents' age
      as the time axis. RESULTS: Offspring birth weight (adjusted for gestational age)
      was inversely associated with all-cause mortality and cardiovascular mortality in
      the parents, with weaker associations for fathers than for mothers. The inverse
      association between birth weight and cardiovascular disease mortality was
      greatest for parents who died at younger ages. Cancer and alcohol-related causes
      of death were also related to offspring birth weight. A sensitivity analysis
      suggests that confounding by smoking is unlikely to entirely explain the
      associations. CONCLUSION: Associations between offspring birth characteristics
      and parents' mortality could, at least in part, reflect genetic factors that
      influence both birth weight and cardiovascular disease risk.

PMID- 15951677
TI  - Daily intake of magnesium and calcium from drinking water in relation to
      myocardial infarction.
AB  - BACKGROUND: A decreased risk for cardiovascular disease has been related to the
      hardness of drinking water, particularly high levels of magnesium. However, the
      evidence is still uncertain, especially in relation to individual intake from
      water. METHODS: We used data from the Stockholm Heart Epidemiology Program, a
      population-based case-control study conducted during 1992-1994, to study the
      association between myocardial infarction and the daily intake of drinking water
      magnesium and calcium. Our analyses are based on 497 cases age 45-70 years, and
      677 controls matched on age, sex, and hospital catchment area. Individual data on
      magnesium, calcium, and hardness of the domestic drinking water were assessed
      from waterwork registers or analyses of well water. RESULTS: After adjustment for
      the matching variables and smoking, hypertension, socioeconomic status, job
      strain, body mass index, diabetes, and physical inactivity, the odds ratio for
      myocardial infarction was 1.09 (95% confidence interval = 0.81-1.46) associated
      with a tap water hardness above the median (>4.4 German hardness degrees) and
      0.88 (0.67-1.15) associated with a water magnesium intake above the median (>1.86
      mg/d). There was no apparent sign of any exposure-response pattern related to
      water intake of magnesium or calcium. CONCLUSIONS: This study does not support
      previous reports of a protective effect on myocardial infarction associated with
      consumption of drinking water with higher levels of hardness, magnesium, or
      calcium.

PMID- 15951679
TI  - Web-based and mailed questionnaires: a comparison of response rates and
      compliance.
AB  - BACKGROUND: We assessed response rates and compliance for a printed questionnaire
      and a Web questionnaire in a Swedish population-based study and explored the
      influence of adding personalized feedback to the Web questionnaire. METHODS: We
      assigned 875 subjects to 1 of 3 groups: printed questionnaire, plain Web
      questionnaire, or Web questionnaire with personalized feedback. The questionnaire
      had 2 parts, first a general section and then a dietary section. RESULTS: The
      response rate for the general section was 64% for the printed questionnaire,
      compared with 50% for the Web questionnaire with feedback. For the dietary
      questionnaire, the rates were reversed, resulting in a total response rate for
      the dietary questionnaire that did not differ between printed and web
      questionnaire with feedback. CONCLUSIONS: Interactivity in the Web questionnaire
      increased compliance in completion of the second section of the questionnaire.
      Web questionnaires can be useful for research purposes in settings in which
      Internet access is high.

PMID- 15951680
TI  - A practical method for collecting 3-day food records in a large cohort.
AB  - BACKGROUND: Recent studies suggest that diet records are more valid measures of
      nutrient intake than are food-frequency questionnaires. However, food records are
      considered unsuitable for large studies due to the need to train participants and
      to review and correct completed records. METHODS: We evaluated a self
      administered 3-day food record protocol in Washington State. One hundred men and
      women age 50-76 years were mailed a food record and serving-size booklet. Sixty
      five people returned a completed food record and were subsequently interviewed to
      obtain missing information. The food records were analyzed with and without added
      information from the interview. RESULTS: The most common error was incomplete
      description, which affected 8% of recorded foods. Differences in mean nutrient
      intake between the uncorrected and corrected records were within 5%, and nutrient
      estimates from the 2 methods were highly correlated. CONCLUSIONS: This
      streamlined protocol yielded data comparable to those collected by more
      burdensome protocols, suggesting that the use of food records may be feasible in
      large cohort studies.

PMID- 15951681
TI  - Hypospadias in sons of women exposed to diethylstilbestrol in utero.
AB  - BACKGROUND: Diethylstilbestrol (DES) is a synthetic estrogen that was widely
      prescribed to pregnant women before 1971. DES increases the risk of breast cancer
      in women who took the drug and the risk of reproductive tract abnormalities in
      their offspring. Dutch investigators have reported a 20-fold increase in risk of
      hypospadias among sons of women who were exposed to DES in utero. We assessed
      this relation in data from an ongoing study of DES-exposed persons. METHODS:
      Several U.S. cohorts of women with documented exposure in utero to DES have been
      followed by mailed questionnaires since the 1970s. Comparison subjects are
      unexposed women of the same ages. In 1997, participants were asked about
      congenital abnormalities in their children. We calculated prevalence odds ratios
      for the risk of hypospadias in sons of exposed mothers relative to sons of
      unexposed mothers using generalized estimating equations to adjust for multiple
      sons per mother and controlling for maternal age at the son's birth. RESULTS: We
      obtained data from 3916 exposed and 1746 unexposed women. These women reported a
      total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The
      prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95%
      confidence interval = 0.4-6.8). CONCLUSIONS: Our findings do not support a
      greatly increased risk of hypospadias among the sons of women exposed to DES in
      utero, as has been previously reported.

PMID- 15951682
TI  - Smoking and Helicobacter pylori infection in a sample of U.S. adults.
AB  - BACKGROUND: Although the prevalence of Helicobacter pylori infection has been
      assessed in the National Health and Nutritional Examination Survey (NHANES), its
      possible relation with smoking has not been fully explored. METHODS: We used the
      1999-2000 NHANES data to examine whether smoking affects the prevalence of H.
      pylori infection in adults (n = 3689). The prevalence of H. pylori infection, as
      assessed by anti-H. pylori IgG enzyme-linked immunoassay, was computed according
      to smoking history and levels of serum cotinine. RESULTS: Current smoking was
      associated with an increased prevalence of H. pylori infection (prevalence odds
      ratio =1.9; 95% confidence interval = 1.4-2.5) after controlling for possible
      confounders. Current smoking, as measured by increased serum cotinine, was also
      associated with an increased prevalence of H. pylori infection (1.6; 1.3-2.0).
      There was no evidence of a dose-response relation. CONCLUSIONS: Smoking may
      contribute to the persistence of H. pylori infection.

PMID- 15951683
TI  - Is the natural twinning rate still declining?

PMID- 15951684
TI  - Mediation proportion.

PMID- 15951685
TI  - Case-crossover studies.

PMID- 15951687
TI  - Population risk measures.

PMID- 15951688
TI  - Too hot to handle.

PMID- 15951689
TI  - Radiation effectiveness factors for use in calculating probability of causation
      of radiogenic cancers.
AB  - This paper presents so-called radiation effectiveness factors that are intended
      to represent the biological effectiveness of different radiation types, relative
      to high-energy Co gamma rays, for the purpose of estimating cancer risks and
      probability of causation of radiogenic cancers in identified individuals.
      Radiation effectiveness factors are expressed as subjective probability
      distributions to represent uncertainty that arises from uncertainties in
      estimates of relative biological effectiveness obtained from radiobiological
      studies of stochastic endpoints, limited data on biological effectiveness
      obtained from human epidemiological studies, and other judgments involved in
      evaluating the applicability of available information to induction of cancers in
      humans. Primarily on the basis of reviews and evaluations of available data by
      experts, probability distributions of radiation effectiveness factors are
      developed for the following radiation types: neutrons of energy less than 10 keV,
      10-100 keV, 0.1-2 MeV (including fission neutrons), 2-20 MeV, and greater than 20
      MeV; alpha particles of any energy emitted by radionuclides; photons of energy 30
      250 keV and less than 30 keV; and electrons of energy less than 15 keV. Photons
      of energy greater than 250 keV and electrons of energy greater than 15 keV are
      assumed to have the same biological effectiveness as reference Co gamma rays and
      are assigned a radiation effectiveness factor of unity, without uncertainty. For
      neutrons and alpha particles, separate probability distributions of radiation
      effectiveness factors are developed for solid tumors and leukemias, and small
      corrections to represent an inverse dose-rate effect are applied to those
      distributions in cases of chronic exposure. A radiation effectiveness factor
      different from unity for 15-60 keV electrons is discussed but is not adopted due
      to a lack of relevant radiobiological data. Radiation effectiveness factors
      presented in this paper are incorporated in the Interactive RadioEpidemiological
      Program and were developed for use by The National Institute for Occupational
      Safety and Health and U.S. Department of Labor in evaluating claims for
      compensation for radiogenic cancers by workers at U.S. Department of Energy
      facilities.

PMID- 15951690
TI  - Uncertainties analysis of doses resulting from chronic inhalation of plutonium at
      the Mayak production association.
AB  - A method is presented to determine the uncertainties in the reported dose due to
      incorporated plutonium for the Mayak Worker Cohort. The methodology includes
      errors generated by both detection methods and modeling methods. To accomplish
      the task, the method includes classical statistics, Monte Carlo, perturbation,
      and reliability groupings. Uncertainties are reported in percent of reported dose
      as a function of total body burden. The cohort was initially sorted into six
      reliability groups, with "A" being the data set that the investigators are most
      confident is correct and "G" being the data set with the most ambiguous data.
      Categories were adjusted based on preliminary calculation of uncertainties using
      the sorting criteria. Specifically, the impact of transportability (the parameter
      used to describe the transport of plutonium from the lung to systemic organs) was
      underestimated, and the structure of the sort was reorganized to reflect the
      impact of transportability. The finalized categories are designated with Roman
      numerals I through V, with "I" being the most reliable. Excluding Category V
      (neither bioassay nor autopsy), the highest uncertainty in lung doses is for
      individuals from Category IV-which ranged from 90-375% for total body burdens
      greater than 10 Bq, along with work histories that indicated exposure to more
      than one transportability class. The smallest estimated uncertainties for lung
      doses were determined by autopsy. Category I has a 32-38% uncertainty in the lung
      dose for total body burdens greater than 1 Bq. First, these results provide a
      further definition and characterization of the cohort and, second, they provide
      uncertainty estimates for these plutonium exposure categories.

PMID- 15951691
TI  - An analysis of variables influencing the number of radiation overexposure events
      in Texas from 1970 to 2000.
AB  - Sources of radiation are used in a variety of modern work settings, including
      industrial, medical, research, and agricultural applications. Although regulatory
      controls exist to limit radiation exposures in these different settings,
      instances of radiation doses in excess of acceptable limits (referred to as
      overexposures) do occur. A unique study examined overexposure events in Texas
      over a 45-y period from 1956 to 2001. The primary purpose of the study was to
      characterize the factors associated with overexposure events. As part of this
      characterization, an interesting trend in the number of overexposures by year was
      observed, but not completely explained. The data revealed a dramatic increase in
      the number of overexposure events, followed by three apparent phases of decline.
      These declines are of particular interest because, while the increase and
      subsequent decrease in overexposures occurred, the number of permits to possess
      radiation sources in Texas generally increased over the same time period. This
      study focused on the identification of the factors that led to the trends in
      overexposure events. Data describing the reported overexposure events in Texas
      from 1970 to 2000 were obtained from the Texas Department of Health Bureau of
      Radiation Control (TDH BRC) and entered into a computerized database. With the
      assistance of senior members of the TDH BRC, the three primary factors
      influencing the number of overexposures were identified. These included domestic
      oil and gas exploration and production from 1970 to 2000, wherein sources of
      radiation are employed in various operations; the establishment of a training and
      certification requirement for industrial radiographers during the period of 1986
      to 1988; and modification of the applicable regulations between 1992 and 1994.
      The generally accepted indicator of oil and gas exploration and production
      activity, known as "rig count," is the measure of the number of active oil and
      gas exploration and production platforms at any given time. Rig count is a
      parameter of particular interest in Texas because the state's economy is
      significantly tied to the market value of this important natural resource. The
      rig count parameter was shown to have a strong correlation with overexposure
      events (Pearson correlation coefficient of 0.82, p < 0.0001). Interestingly, the
      sources causing the overexposures indicate that the events stem primarily not
      from the oil and gas exploration activity itself, but rather from support
      activities in the form of industrial radiographic procedures. The number of
      overexposure events was also determined to be influenced by the imposition of the
      training requirement for radiographers and the modification of the applicable
      regulations (e.g., the elimination of the quarterly dose limit). The relative
      magnitude of these influences, however, was far overshadowed by the identified
      predominant predictor of rig count. The determination of rig count as the
      significant influencing factor in overexposure events is useful in possibly
      recognizing the potential for future occurrences of the same nature. This
      assessment also serves to highlight an apparent significant public health success
      story, as the number of overexposures per radioactive material licensee is shown
      to have declined significantly over the 30-y period of study. The factors
      contributing to this phenomenon are described to serve as a model for use in
      other settings.

PMID- 15951692
TI  - The effective dose equivalent and effective dose for hot particles on the skin.
AB  - Whole body exposure from photon-emitting hot particles is a relatively new
      problem. Until recently, the U.S. Nuclear Regulatory Commission required the use
      of deep dose equivalent (DDE) to estimate and report whole body exposures from
      hot particles. In this study, effective dose equivalent (EDE) and effective dose
      (ED) were calculated for point sources with photon energies between 0.1 MeV to
      2.0 MeV for 74 locations covering the entire body surface, using the MCNP code
      and the MIRD-type stylized phantoms. Tabulated data show that the sources located
      near the upper chest and the lower waist have the highest EDE and ED, while
      sources near the top of head and feet yielded the smallest. The calculated DDE
      values are much higher than the EDE values. For an exposure of 75 microCi h(-1)
      to a 60Co source located at the center upper chest area, the EDE is 36.5 microSv
      (3.65 mrem), which is a factor of 240 smaller than the corresponding DDE. EDE and
      ED data are tabulated for quick reference by users in nuclear power plants.

PMID- 15951693
TI  - An analysis of differences in the low-frequency electric and magnetic field
      exposure standards of ices and ICNIRP.
AB  - Technical factors accounting for differences in low-frequency (0-3 kHz) standards
      of IEEE C95.6 and ICNIRP are identified. These factors are related to thresholds
      of adverse reactions, safety factors, probability factors, thresholds for
      different tissue types, magnetic induction models, and induced current and spark
      discharges with E-field exposure. This paper summarizes technical factors
      accounting for differences between the two standards and recommends resolution of
      those factors.

PMID- 15951694
TI  - Toxicity of uranium and the removal effects of CBMIDA and EHBP in simulated
      wounds of rats.
AB  - We examined the acute toxicity of uranium (99.3% 238U, 0.7% 235U) and the effects
      of Catechol-3,6-bis(methyleiminodiacetic acid) (CBMIDA) and Ethane-1-hydroxy-1,1
      bisphosphonate (EHBP) on the removal of uranium after intramuscular injection as
      a simulated wound intake in rats. In this experiment, male Wistar rats, 8 wk old,
      were injected intramuscularly with uranyl nitrate in the femoral muscles.
      Experiment I: Rats died from 3 to 7 d after they were injected with five doses of
      7.9, 15.8, 31.5, 63, and 126 mg kg(-1) uranium. The uranium retained 8.4-13.6% of
      the injected doses in the kidneys, showing the relationship between the injected
      dose and the retained concentration (r = 0.997). The excretion rates of the
      injected doses in the 63 and 126 mg kg(-1) uranium-injected rats were 1.73% and
      3.09% in urine and 0.81% and 1.06% in feces on the first day, and 0.54% and 0.56%
      in feces on the second day, respectively. Experiment II: The retention of uranium
      at 1, 3, 6, and 24 h was examined after rats were injected with 63 mg kg(-1)
      uranium. The concentration of uranium decreased in the plasma, while it increased
      in the kidneys and femur until 6 h, and it continued to increase in the liver
      until 24 h. Experiment III: Rats were divided into four groups (n = 10) and were
      injected with a dose of 2 mg kg(-1) uranium. Two of the groups were then injected
      intraperitoneally with 240 or 480 mg kg-1 CBMIDA, and one group was injected with
      10 mg kg(-1) EHBP once daily for 28 d, beginning 1 h after uranium injection on
      the first day. The fourth group was the non-treated control group. The survival
      rates at the end of the experiment were 80% and 40% in the 240 and 480 mg kg(-1)
      CBMIDA groups, 50% in the EHBP group, and 20% in the non-treated group. The
      successive administration of chelating agents was effective in decreasing the
      concentration of uranium in the kidneys, bone, and liver. The results indicated
      that uranium induces acute death and renal dysfunction by chemical toxicity, and
      both CBMIDA and EHBP were effective agents to prevent these effects.

PMID- 15951695
TI  - A survey of IAEA/WHO 60Co TLD postal dose intercomparison exercises during 1985
      2003.
AB  - Results of the survey of IAEA/WHO Co postal dose intercomparison exercises in
      which the Secondary Standard Dosimetry Laboratory participated during the period
      1985-2003 are presented. In 14 exercises spread over a period of 19 years, the
      deviation in therapy dose level measurements of the Secondary Standard Dosimetry
      Laboratory has never exceeded the International Atomic Energy Agency Dosimetry
      Laboratory acceptable levels of accuracy. The IAEA/WHO thermoluminescent
      dosimeter postal dose intercomparison service, the procedure for irradiation of
      thermoluminescent dosimeters, and the water absorbed dose determination are
      briefly described.

PMID- 15951696
TI  - Calcium iodate-another effective blocker of radioiodine uptake by the thyroid
      gland.
AB  - KI and KIO3 are the commonly used prophylactic drugs for the protection of
      thyroid glands against radioiodine. In this study, we have demonstrated the use
      of another iodine containing salt, calcium iodate [Ca(IO3)2], as an effective
      blocker of radioiodine uptake by the thyroid gland in rats. Ca(IO3)2 is permitted
      by the FDA as a food additive and is "generally regarded as safe" (GRAS, CFR
      No.1206). We have also compared the efficacy of Ca(IO3)2 with KIO3 in blocking
      thyroidal uptake of radioiodine, which could be important considering the better
      shelf life of Ca(IO3)2. Laboratory rats were administered 131I and stable iodide
      in the form of KIO3 or Ca(IO3)2 was given orally, 2 h after the administration of
      131I. All the animals were monitored for whole body retention (WBR) of 131I, at
      24 h and further for 14 d. The results of the present study provide us with
      evidence that Ca(IO3)2 can serve as another promising radioiodine blocker, and is
      as equipotent as KI/KIO3 in protecting the thyroid gland. We have not found any
      studies that examined the property of Ca(IO3)2 in blocking radioiodine uptake by
      the thyroid gland and the present study is an attempt in this direction.

PMID- 15951700
TI  - Improving patient flow and overcrowding in emergency departments.

PMID- 15951701
TI  - The positive effects of surgical services redesign.

PMID- 15951702
TI  - The multigenerational nursing work force: essential differences in perception of
      work environment.

PMID- 15951703
TI  - Hospital charity care and billing practices: the labor movement pans for gold.
AB  - Labor unions and legislators are accusing some hospitals of discriminatory
      billing practices, overbilling the poor, and using humiliating collection
      practices. The authors focus on the unions targeting healthcare, the litigation,
      and how these unions are using these issues to advance organizing. Healthcare
      executives need to empower their employees with information on how money is spent
      at their organizations to further the organization's mission, vision, and values.

PMID- 15951704
TI  - Nurse-sensitive patient outcomes: an annotated bibliography.
AB  - This article is an annotated bibliography on the topic of nurse staffing and
      patient care outcomes in the acute care setting. The authors have been involved
      in the developmental and pilot phase of the Veterans Affairs Nursing Outcomes
      Database project to build a database of acute care nursing-sensitive quality
      indicators. In the section preceding the annotated bibliography, a context for
      the development of this literature review is explained and a summary synthesizing
      key issues is presented.

PMID- 15951705
TI  - Presenteeism in nursing: a clear and present danger to productivity.
AB  - Over the last decade, economists have identified that presenteeism, the first
      cousin of absenteeism, occurs when employees show up for work but, because of
      mental or medical illness, do not function productively or perform at 100%.
      Research has begun to identify nursing as an occupational group with high
      presenteeism. The author discusses the etiology and potential solutions for
      managing this new component in the productivity equation and in addressing
      depression, the major contributor to presenteeism.

PMID- 15951706
TI  - The linkage between psychological capital and commitment to organizational
      mission: a study of nurses.
AB  - A variety of studies demonstrate a clear linkage between the positive
      psychological capacities of employees and desirable workplace outcomes. However,
      to date, little empirical research exists which has examined this relationship.
      Given current and projected challenges in healthcare industry, the need for
      nurses who are committed to the mission of their organization has never been more
      critical. The authors report findings from a study designed to examine the
      important linkage between nurses' self-reported positive psychological capital
      (PsyCap) and their "intentions to stay" as well as their supervisors' ratings of
      their commitment to the mission of the organization. The authors found a highly
      significant positive relationship between PsyCap and the "intentions to stay" and
      commitment to the mission, values, and goals of the hospital. Practical
      implications for effectively managing PsyCap in the workplace are presented.

PMID- 15951707
TI  - Nurses' views on work enabling factors.
AB  - OBJECTIVE: In this study nurses' views on work enabling factors, priority issues
      for improvement, and stress and satisfaction levels were examined. BACKGROUND:
      This research builds on previous work studies that empirically established work
      dimension indices related to individual and organizational outcomes. A survey
      tool was adapted so it replicated previous instrument development research, as
      well as explored its practicality as a benchmark and process tool in healthcare
      organizations. METHODS: A descriptive design was used in a single institution
      employing a self-report survey. RESULTS: All of the enabling factors were found
      to be important to nurses. The lowest-rated factors related to manager-staff
      relationships, congruent with open-ended responses that identified improving
      management as the highest priority. Unlike previous studies, job insecurity and
      trust were not issues, and nurses predominantly (92%) reported that quality care
      was provided. CONCLUSIONS: A simple enabling index and survey tool can be used to
      proactively assess work environments, so that conditions can be improved before
      they lead to morale, sickness, and retention problems. The survey results provide
      important feedback that can prompt discussions about how workplaces can become
      healthier, more productive, and rewarding places for nurses.

PMID- 15951711
TI  - Do subject characteristics modify the effects of particulate air pollution on
      daily mortality among the elderly?

PMID- 15951712
TI  - Respiratory protection for mold remediation.

PMID- 15951714
TI  - The assessment of chronic health conditions on work performance, absence, and
      total economic impact for employers.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence and
      estimate total costs for chronic health conditions in the U.S. workforce for the
      Dow Chemical Company (Dow). METHODS: Using the Stanford Presenteeism Scale,
      information was collected from workers at five locations on work impairment and
      absenteeism based on self-reported "primary" chronic health conditions. Survey
      data were merged with employee demographics, medical and pharmaceutical claims,
      smoking status, biometric health risk factors, payroll records, and job type.
      RESULTS: Almost 65% of respondents reported having one or more of the surveyed
      chronic conditions. The most common were allergies, arthritis/joint pain or
      stiffness, and back or neck disorders. The associated absenteeism by chronic
      condition ranged from 0.9 to 5.9 hours in a 4-week period, and on-the-job work
      impairment ranged from a 17.8% to 36.4% decrement in ability to function at work.
      The presence of a chronic condition was the most important determinant of the
      reported levels of work impairment and absence after adjusting for other factors
      (P < 0.000). The total cost of chronic conditions was estimated to be 10.7% of
      the total labor costs for Dow in the United States; 6.8% was attributable to work
      impairment alone. CONCLUSION: For all chronic conditions studied, the cost
      associated with performance based work loss or "presenteeism" greatly exceeded
      the combined costs of absenteeism and medical treatment combined.

PMID- 15951715
TI  - The effects of a worksite chronic disease prevention program.
AB  - OBJECTIVE: This study determined the behavioral and clinical impact of a worksite
      chronic disease prevention program. METHODS: Working adults participated in
      randomized clinical trial of an intensive lifestyle intervention. Nutrition and
      physical activity behavior and several chronic disease risk factors were assessed
      at baseline, 6 weeks, and 6 months. RESULTS: Cognitive understanding of the
      requirements for a healthy lifestyle increased at the end of the program. Program
      participants significantly improved their cognitive understanding of good
      nutrition and physical activity and had significantly better nutrition and
      physical activity behavior at both 6 weeks and 6 months. Participants had
      significantly lower body fat, blood pressure, and cholesterol. CONCLUSIONS: This
      worksite chronic disease prevention program can significantly increase health
      knowledge, can improve nutrition and physical activity, and can improve many
      employee health risks in the short term.

PMID- 15951716
TI  - The prevalence and effects of adult attention deficit/hyperactivity disorder on
      work performance in a nationally representative sample of workers.
AB  - OBJECTIVE: The prevalence and workplace consequences of adult attention
      deficit/hyperactivity disorder (ADHD) are unknown. METHODS: An ADHD screen was
      included in a national household survey (n = 3198, ages 18-44). Clinical re
      interviews calibrated the screen to diagnoses of Diagnostic and Statistical
      Manual of Mental Disorders, 4th edition ADHD. Diagnoses among workers were
      compared with responses to the WHO Health and Work Performance Questionnaire
      (HPQ). RESULTS: A total of 4.2% of workers had ADHD. ADHD was associated with
      35.0 days of annual lost work performance, with higher associations among blue
      collar (55.8 days) than professional (12.2 days), technical (19.8 days), or
      service (32.6 days) workers. These associations represent 120 million days of
      annual lost work in the U.S. labor force, equivalent to dollar 19.5 billion lost
      human capital. CONCLUSIONS: ADHD is a common and costly workplace condition.
      Effectiveness trials are needed to estimate the region of interest of workplace
      ADHD screening and treatment programs.

PMID- 15951717
TI  - Plasma concentrations of retinol, carotene, and vitamin E and mortality in
      subjects with asbestosis in a cohort exposed to crocidolite in Wittenoom, Western
      Australia.
AB  - OBJECTIVE: We sought to examine the relationships between plasma concentrations
      of retinol, carotene, and vitamin E and mortality associated with asbestosis in
      people previously exposed to crocidolite. METHODS: Cox regression modeling was
      applied to examine these relationships at the first measurement of each vitamin,
      at the measurement at each visit, and with the rate of change of each vitamin
      during the follow-up. RESULTS: There were 76 deaths of people with asbestosis
      during the follow-up period and 1885 subjects censored. Mortality in subjects
      with asbestosis was inversely related to plasma levels of retinol and Vitamin E
      concentrations and to their rate of increase during the follow-up. Carotene
      concentrations at first visit were associated with lower mortality but not during
      the follow up period. CONCLUSIONS: Chronically low levels of these vitamins are
      associated with an increased risk of dying with asbestosis.

PMID- 15951718
TI  - Risk of tuberculosis in correctional healthcare workers.
AB  - OBJECTIVE: The objective of this study was to determine the prevalence,
      incidence, and risk factors for occupational infection with tuberculosis among
      healthcare workers employed in correctional facilities. METHODS: The authors
      conducted a self-administered survey, clinical interview, and tuberculin skin
      testing. RESULTS: The overall tuberculin skin test point prevalence rate was
      17.7%, the reactivity rate was 2.2%, and the annual incidence was 1.3%. At the
      multivariate level, after controlling for bacille Calmette-Guerin vaccination,
      only origin of birth remained significantly associated with prevalence of
      tuberculosis infection. CONCLUSIONS: Although the prevalence of tuberculin
      reactivity was high in this population, the risk factors were predominantly
      demographic rather than occupational. Nevertheless, continued vigilance to
      control occupational exposure to this and other respiratory pathogens is
      warranted, given the potential for future outbreaks of tuberculosis, as well as
      other known and emerging airborne pathogens.

PMID- 15951719
TI  - Clinical activities in an academic hospital-based occupational medicine program.
AB  - OBJECTIVES: The objectives of this article are to characterize the clinical
      activities encountered by a large academic hospital-based occupational medicine
      program and to discuss their implications for occupational medicine residency
      training and the training of practicing physicians. METHODS: Clinical activities
      from July 1, 1996, to December 31, 2004, were retrieved from computerized
      databases and categorized. All morbidity coding was performed using the same
      classification scheme and resource. RESULTS: The largest volume of clinical
      activities included patients seen for physical examinations, work-related injury
      and illness care, and substance abuse testing. The most frequently encountered
      workers' compensation cases were musculoskeletal. CONCLUSIONS: Although medical
      surveillance examinations, toxic exposure assessments, and other specialty
      services were available, the demand for such services was relatively low.

PMID- 15951720
TI  - Development and validation of a scale to measure work-related fatigue and
      recovery: the Occupational Fatigue Exhaustion/Recovery Scale (OFER).
AB  - OBJECTIVE: Various empirical studies link persistent failure to recover from
      acute fatigue to the evolution of chronic fatigue. However, existing fatigue
      measurement scales do not tend to distinguish between acute and chronic fatigue
      elements well, and none include a measure of effective recovery from fatigue.
      METHODS: The 15 item Occupational Fatigue Exhaustion Recovery (OFER) scale has
      been developed and validated in three study populations specifically to measure
      work-related fatigue. RESULTS: The OFER scale possesses robust, gender-bias free
      psychometric characteristics. Its three subscales identify and distinguish
      between chronic work-related fatigue traits, acute end-of-shift states and
      effective fatigue recovery between shifts. CONCLUSION: These studies confirm the
      mediating role of intershift-shift recovery in the evolution of adaptive end-of
      shift fatigue states to maladaptive persistent fatigue traits. The OFER scale is
      suggested as a potentially valuable new tool for use in work-related fatigue
      research.

PMID- 15951721
TI  - Characterizing the burden of occupational injury and disease.
AB  - OBJECTIVES: To review the literature on the burden of occupational disease and
      injury and to provide a comprehensive characterization of the burden. METHODS:
      The scientific and governmental literature from 1990 to the present was searched
      and evaluated. Thirty-eight studies illustrative of the burden of occupational
      disease were reviewed for findings, methodology, strengths, and limitations.
      RESULTS: Recent U.S. estimates of occupational mortality and morbidity include
      approximately 55,000 deaths (eighth leading cause) and 3.8 million disabling
      injuries per year, respectively. Comprehensive estimates of U.S. costs related to
      these burdens range between dollar 128 billion and dollar 155 billion per year.
      Despite these significant indicators, occupational morbidity, mortality, and
      risks are not well characterized in comparative burden assessments. CONCLUSIONS:
      The magnitude of occupational disease and injury burden is significant but
      underestimated. There is a need for an integrated approach to address these
      underestimates.

PMID- 15951722
TI  - Work environment and occupational health of dental hygienists: a qualitative
      assessment.
AB  - OBJECTIVE: We sought to characterize the work environment and identify factors
      that influence the occupational health of dental hygienists. METHODS: We
      conducted a qualitative analysis of dental hygiene work based on five national
      focus groups. RESULTS: We found that musculoskeletal symptoms are common,
      particularly after 10 years; common ergonomic problems included instruments and
      chairs. Important non-physical workplace problems include role ambiguity (eg,
      employee vs. independent practitioner), inadequate recognition, role identity
      (eg, distinction from dental assistants), role conflict (eg, with dentists and
      spousal office managers), and social isolation. CONCLUSIONS: Work organizational
      factors (eg, frequent part-time work, inadequate breaks, perception as a "second
      team" distinct from the dentist and dental-assistant team) impede the remediation
      of ergonomics and other problems. Job flexibility encourages hygienists to change
      work hours or location rather than deal with work conditions. Occupational health
      interventions should address social environment and work organization.

PMID- 15951723
TI  - Work environment of dental hygienists.
AB  - OBJECTIVE: We sought to evaluate how musculoskeletal disorders and workplace
      psychosocial factors affect dental hygienists' work hours and productivity.
      METHODS: We mailed a survey to dental hygienists in Los Angeles and Orange
      Counties, California. RESULTS: Musculoskeletal pain caused 27% of hygienists to
      decrease work hours and 8.7% to change office locations. Hand/wrist pain caused
      the most missed workdays. Conversely, conflicts with the dentist caused 28.2% of
      dental hygienists to change jobs and 12.7% to decrease work hours. Conflicts with
      staff caused 17.1% to change office locations but only 7.0% to decrease work
      hours. This pattern was confirmed with multiple logistic regression analyses.
      CONCLUSIONS: Musculoskeletal and psychosocial factors affect dental hygienists
      differently: musculoskeletal discomfort is more likely to cause dental hygienists
      to decrease their working hours, whereas professional and social conflicts are
      more likely to lead to change in work location.

PMID- 15951727
TI  - Salvage therapy.

PMID- 15951724
TI  - Does occupation explain gender and other differences in work-related eye injury
      hospitalization rates?
AB  - OBJECTIVE: We sought to determine whether demographic differences in eye injury
      rates persist after adjusting for occupational exposure. METHODS: On-duty eye
      injury hospitalizations were linked to occupation among active-duty US Army
      personnel. RESULTS: Eye injury rates were higher for white soldiers, men, and for
      younger soldiers, even after adjusting for occupational group and specific job
      titles using multivariate models. CONCLUSIONS: This finding contrasts with
      studies of other injuries, suggesting that occupation does not fully account for
      variations in eye injury risk. Because protective eye-wear can prevent most
      serious eye injuries, we hypothesize that differences in protective eye-wear use
      between men and women may contribute to differences in eye injury rates, although
      follow-up studies are needed to confirm this. Prevention efforts should consider
      targeting high-risk demographic groups in addition to high-risk occupations.

PMID- 15951728
TI  - The clinical significance of viral fitness.
AB  - Increasing evidence indicates that antiretroviral drug resistance is associated
      with impaired viral fitness and that this impairment can translate, at least
      transiently, into a virological and immunological benefit. The optimal strategies
      for exploiting the fitness cost associated with drug resistance remain to be
      determined. For highly drug-experienced patients receiving salvage therapy with a
      detectable viral load and with limited or no remaining drug options, continuing
      the current regimen may be a useful strategy to delay disease progression. In
      this context, it remains controversial whether it is preferable to continue
      failing therapy with nucleoside reverse transcriptase inhibitors, protease
      inhibitors or both.

PMID- 15951729
TI  - New drugs for old.
AB  - The use of highly active antiretroviral therapy (HAART) has led to the emergence
      of viral isolates with resistance-associated mutations. Currently, new cases of
      highly resistant HIV infections associated with rapid progression to AIDS are
      being reported. The features of a new drug for HIV treatment must include
      selective potent activity against wild-type virus as well as against mutant virus
      that has been selected by the use of current antiretroviral treatment regimens.
      As patients in industrialised countries may live with HIV infection for decades,
      new drugs must also encourage adherence with simplified dosing regimens
      associated with favourable toxicity profiles. The replacement of older therapies
      with newer drugs that avoid cross resistance, even within the same class of
      antiretroviral, represents a new hope in retroviral targeting.

PMID- 15951730
TI  - New drugs.

PMID- 15951731
TI  - Medical therapy of prostate cancer. A review.
AB  - Androgen ablation or blockade of androgen action through the androgen receptor
      (AR) has been the cornerstone of treatment of advanced prostate cancer. The
      relative merits of monotherapy or combined androgen blockade (CAB) are still the
      subject of debate. Each treatment strategy/hormonal agent has favourable and
      unfavourable effects. Patients with advanced prostate cancer will clearly benefit
      androgen deprivation-based treatment for palliating their symptoms and for
      improving their quality of life (QOL). However, whether these therapies prolong
      survival when administered before there are symptoms caused by disease
      progression remains controversial. Data from multiple recent studies indicate
      that an earlier treatment in patient's disease course likely leads to better
      outcome, but it is not easy to predict the best timing of hormonal therapy for
      asymptomatic advanced disease. For the purpose of delaying the onset of androgen
      independent growth of prostate cancer, different regimen of intermittent androgen
      blockade (IAB) have been applied to patients. The use of IAB is increasing but,
      despite theoretical advantages in terms of patient QOL, clinical studies have yet
      to prove superiority over continuous therapy. The role of androgen deprivation in
      combination with surgery or radiotherapy has been also evaluated. While
      neoadjuvant hormonal therapy (NHT) can significantly decrease the incidence of
      positive margins at the time of radical prostatectomy (RP), 3 months of treatment
      is not long enough to have any significant effect on biochemical recurrence
      rates. The results of studies investigating longer courses (8 months) of NHT are
      awaited. High-risk patients should be considered for early adjuvant hormonal
      therapy (AHT) after surgery, as they may be most likely to benefit. The rationale
      for the use of NHT in combination with radiotherapy is that it reduces tumour
      volume and therefore the amount of radiation therapy that is needed to treat the
      tumour. It has been found that 3-4 months of hormonal treatment reduces prostate
      volume by 25-50%. Intermediate-risk patients treated with NHT and concomitant
      hormonal therapy have been found to have a 94% freedom for biochemical failure
      after 4 years, suggesting that this group is the ideal patient population to
      receive short-term hormonal therapy in combination with brachytherapy. Several
      studies suggested the current consensus that patients with clinically localized
      or locally advanced high-grade tumours benefit from definitive radiation therapy
      and long-term AHT. The current treatment for advanced prostate cancer remains
      essentially palliative. However, an increased understanding of the heterogeneous
      nature of the disease, the mechanisms that lead to hormone-refractory prostate
      cancer (HRPC) has identified novel therapeutic targets and led to the development
      of selective new therapies, that may help to prolong survival and maintain QOL
      for patients with HRPC.

PMID- 15951733
TI  - Sperm and assisted reproduction.
AB  - When optimization of the male and female partner has failed, techniques of
      assisted reproduction may be employed. Their common rationale is to enhance the
      probability of fertilization by bringing the spermatozoa closer to the oocyte(s).
      Assisted reproductive techniques are not a curative treatment but they intend to
      circumvent some functional deficits in gametes. The choice of the most
      appropriate assisted-reproduction treatment for the individual couple is often
      based on the quality of the ejaculate or the source of the gametes. Intrauterine
      insemination (IUI) may be considered as the first-line approach when after semen
      preparation at least 1 x 10(6) spermatozoa can be harvested. IVF is to be
      considered when dealing with longstanding infertility in a couple with a normal
      fertility status in the female partner. The choice between IVF and
      intracytoplasmic sperm injection (ICSI) is difficult since performing 3 ICSI
      treatments can prevent one complete fertilization failure even in couples with
      borderline semen characteristics. When less than 1 x 10(6) progressively motile
      spermatozoa are available after preparation, ICSI may be the treatment of choice.
      ICSI can also be performed using surgically-retrieved spermatozoa. In men with
      obstructive azoospermia spermatozoa can be retrieved through different
      techniques. However, in azoospermic men with primary testicular dysfunction,
      excisional biopsies are to be preferred. But even then, spermatozoa may only be
      obtained in about half of these men when no preliminary selection has been made
      on the basis of a diagnostic biopsy. Patients with extreme oligozoospermia or
      azoospermia should be informed about the possible genetic background of their
      condition that is transmissible to their children and about the limitations of
      the currently available genetic screening methods. Although currently there is no
      convincing evidence that ICSI is associated with a substantial higher incidence
      of congenital malformations, we should not draw the premature conclusion that
      ICSI is safe. ICSI must be applied with caution and only when no other treatment
      option is available.

PMID- 15951732
TI  - Erectile dysfunction: molecular biology, pathophysiology and pharmacological
      treatment.
AB  - During the past decade, several progresses have been made for a deeper
      understanding of the regulatory factors that mediate normal erectile function,
      although the mechanisms involved in pathophysiology of erectile dysfunction (ED)
      remain to be completely elucidated. However, dramatic advances in the management
      of ED have occurred. Many drugs are now available, with oral pharmacotherapy
      representing the first-line option for most patients. ED is a common condition
      associated with aging but not necessarily a consequence of aging. The most
      important risk factors are associated to the impaired balance between contractant
      and relaxant mechanisms of penile structures, resulting in arterial insufficiency
      and defect smooth muscle relaxation. The normal erectile function involves the
      synthesis of NO, the main neurotransmitter mediating erectile processes, and the
      subsequent accumulation of cyclic GMP (cGMP). The NO formation, and therefore the
      erection, is strictly controlled by the activity of NO synthase (NOS) isoenzymes,
      whereas cGMP degradation is specifically controlled by phosphodiesterase type 5
      (PDE5), which promotes smooth muscle tone and terminates erection. The regulation
      of the activity of these 2 counteracting enzymes allows the penis to be
      contracted for the majority of the time. Androgens play a pivotal role in these
      mechanisms by regulating both NOS and PDE5 activity. This peripheral and
      antithetic role of androgens seems to regulate penile erections synchronizing
      erectile processes to sexual desire. Moreover, the androgen-dependent activity of
      PDE5 mirrors the unresponsiveness of certain patients with ED to PDE5 inhibitors
      (PDE5i), the most widely prescribed oral drugs. In fact, PDE5i cannot work if the
      target enzyme is lacking. This suggests the importance to test testosterone
      plasma levels in those patients with ED who do not respond to PDE5i. In
      conclusion, a better understanding of the pathogenic factors of ED will be useful
      to appropriately design pharmacotherapy and improve clinical management depending
      on the unique condition of each patient.

PMID- 15951734
TI  - Sperm retrieval for intra-cytoplasmic sperm injection in non-obstructive
      azoospermia.
AB  - Surgical testicular sperm retrieval for intra-cytoplasmic sperm injection (ICSI)
      purposes is the only possibility of biological fathering in case of non
      obstructive azoospermia (NOA). Successful retrieval only correlates with
      histology, not with FSH values or testicular volume. Concurrent AZFa and AZFb
      microdeletion predict unsuccessful recovery. Testicular sperm extraction (TESE)
      (mean of successful retrievals in literature: 52.7%) is the technique of choice:
      we had successful retrievals in 100% of cases of hypospermatogenesis with > 5
      spermatids/tubule (spd/tub), 81.8% of cases of hypospermatogenesis with < 4
      spd/tub, 50% of cases of maturation arrest, and 25% of cases of histologically
      pure Sertoli cell-only syndrome. Microsurgical TESE (mTESE) has been reported to
      increase successful retrievals: from 16.7-45% for standard TESE to 42.9-63.6% for
      mTESE, depending on the distribution of testicular histology in the various case
      studies; from 9 to 14 cases out of 22, respectively, in the only study in which
      TESE and mTESE were performed simultaneously on the same testis. Improvements in
      biological procedures for TESE retrievals can increase positive findings. TeFNA
      does not appear to be indicated in NOA, both because of its low success rates-
      which, in practice, are only positive in hypospermatogenesis--and because it is
      unable to detect any carcinomas in situ. Previous surgery of left varicocele in
      NOA could increase the chances of subsequent recovery. ICSI from TESE has lower
      birth rates in NOA than in obstructive azoospermia (OA) (19% vs 28%). Abortion
      rates are significantly higher following ICSI from NOA (11.5%) than from OA
      (2.5%) (P=0.001). Therefore, the prognostic fertility of a couple with an NOA
      male is quite lower than for a couple with an OA male.

PMID- 15951735
TI  - Laparoscopic renal cryotherapy: biology, techniques and outcomes.
AB  - AIM: The development of minimally invasive approaches to renal cell carcinoma
      (RCC) over the last 10 years has given rise to newer therapies such as renal
      cryotherapy. Patients with significant comorbidities who are not suitable for
      open surgery may be candidates for this procedure. Herein, we review the biology,
      techniques and outcomes of laparoscopic renal cryotherapy as performed at our
      institution. METHODS: We present our initial experience with laparoscopic
      cryotherapy for the treatment of small, peripheral renal lesions and provide a
      review of the literature. A retrospective review was performed on our first 25
      patients treated with transperitoneal laparoscopic cryotherapy for small
      peripheral renal lesions by a single surgeon between 2002 and 2003. RESULTS: We
      treated 25 patients, average age of 65 years (range 32-83) with transperitoneal
      laparoscopic renal cryotherapy for small, enhancing, peripheral lesions
      suspicious for RCC. Mean pretreatment creatinine of 1.06 was unchanged after
      treatment. Mean tumor size was 2.4 cm (range 1.5-3.6 cm), with a mean EBL of 80
      mL. Pathology revealed 72% RCC, 2 oncocytomas, one each arterio-nephrosclerosis,
      inflammatory tissue, focal-segmental glomerulosclerosis, angiomyolipoma and one
      normal tissue specimen. Average tumor grade was 2.3 (range 2-4). Mean hospital
      stay was 2.3 days (range 1-5). Three cases were converted to open. Two
      complications included transfusion and hydronephrosis, both managed
      conservatively. Mean follow-up is 16.2 months (range 6-36 months). There have
      been no recurrences to date despite a rigorous surveillance protocol.
      CONCLUSIONS: Renal cryotherapy is a viable option for nephron sparing surgery in
      small, peripheral, renal lesions. The procedure is well tolerated, may be
      considered in patients who are not good candidates for open surgical approaches,
      results in minimal morbidity, and has very encouraging treatment results. Close
      surveillance post-treatment is essential. Longer follow-up data will be necessary
      to establish the durability of laparoscopic renal cryotherapy.

PMID- 15951736
TI  - Posterior tibial nerve stimulation: is the once-a-week protocol the best option?
AB  - AIM: Aim of our study was to compare the results of posterior tibial nerve
      stimulation (PTNS) performed weekly with those of PTNS performed 3 times per week
      in patients with overactive bladder syndrome. METHODS: Thirty-five patients (28
      females, 7 males) with overactive bladder syndrome not responding to
      antimuscarinic therapy were enrolled in a prospective study. A total of 17 out of
      35 patients were randomly assigned to group A and treated with a PTNS protocol
      based on weekly stimulation sessions; 18 out of 35 patients were randomly
      assigned to group B and treated with a PTNS protocol based on stimulation
      sessions performed 3 times per week. All subjects were evaluated by means of 24 h
      bladder diaries, quality of life questionnaires (I-QoL, SF36) and urodynamic
      evaluation before and after treatment. Patients were asked after each stimulation
      session to give their opinion on the efficacy of the treatment. We have
      considered ''success'' those patients who presented a reduction >50% of the
      micturition episodes/24 h (ME/24) or (if incontinent) of the incontinence
      episodes/24 h (IE/24). Results before and after treatments in both groups were
      collected and statistically compared. RESULTS: As a whole, 11/17 patients (63%)
      in group A and 12/18 patients (67%) in group B were considered ''success''; 4/11
      (36%) incontinent patients in group A and 5/11 (45%) incontinent patients in
      group B were completely cured after treatment. In both groups, patients reported
      subjective improvement after 6-8 stimulation sessions. CONCLUSIONS: Our findings
      seem to show that the periodicity of stimulation does not effect the results of
      PTNS treatment. The advantage of more frequent stimulation sessions is to achieve
      earlier a clinical improvement.

PMID- 15951737
TI  - Primary signet ring cell adenocarcinoma of the bladder.

PMID- 15951739
TI  - Discrepancies between use of antihypertensive drugs and guidelines indications:
      pharmacoeconomic implications.

PMID- 15951738
TI  - Inhibition of retinal and choroidal neovascularization by a novel KDR kinase
      inhibitor.
AB  - PURPOSE: Inhibition of vascular endothelial growth factor (VEGF) signaling has
      shown great promise for the treatment of ocular neovascular disease. Current anti
      VEGF therapies in late-stage development, while efficacious, require dosing by
      frequent intravitreal injections that are inconvenient to patients. VEGF
      signaling inhibitors that demonstrate more convenient dosing regimens could lead
      to the improved treatment of neovascular diseases such as wet age related macular
      degeneration (AMD) and proliferative diabetic retinopathy (PDR). Here we describe
      the assessment of a KDR (VEGFR2) kinase inhibitor in two well-established models
      of ocular neovascularization following oral administration. METHODS: A novel KDR
      kinase inhibitor was dosed by oral gavage for 12 days at 0, 10, 30, or 100 mg/kg
      in an adult male Brown Norway rat laser induced choroidal neovascularization
      (CNV) model. The areas of CNV lesions were quantitated by fluorescence image
      analysis of FITC-dextran perfused animals. The kinase inhibitor was also assessed
      in a rat oxygen induced retinopathy (OIR) model in which neonatal rats were
      placed in an oxygen chamber that delivered alternating 24 h cycles of 50% and 10%
      oxygen for 14 days. After 14 days of oxygen treatment, the animals were returned
      to room air and dosed orally for 7 days with 0, 10, or 30 mg/kg kinase inhibitor.
      The extent of retinal neovascularization was assessed by counting pre-retinal
      neovascular nuclei on histological sections. RESULTS: At doses of 100 mg/kg, the
      KDR kinase inhibitor resulted in a 98% reduction in lesion size in the rat CNV
      model. 30 mg/kg doses of the inhibitor showed a 70% and 80% reduction in lesion
      size in the laser CNV and OIR models, respectively. CONCLUSIONS: Oral dosing of
      the described KDR kinase inhibitor effectively inhibits neovascularization in two
      well-established animal models of ocular neovascularization. These data suggest
      that compounds of this class may prove to be useful for the treatment of a
      variety of ocular neovascular diseases using a convenient oral dosing regimen.

PMID- 15951740
TI  - Patient satisfaction with antihypertensive therapy.
AB  - The objective of the study was to assess factors associated with treatment
      satisfaction among patients receiving antihypertensive therapy. A weighted cross
      sectional online survey was conducted with hypertensive patients participating in
      a chronic disease panel in the US. Patients on monotherapy with medications from
      the following classes were identified: ACE inhibitors (ACEIs), angiotensin
      receptor blockers (ARBs), beta blockers (BBs), calcium channel blockers (CCBs),
      and diuretics. The control group included patients without treatment. Pairwise
      comparisons between groups were conducted for factors that may affect patients'
      satisfaction. The study population had a mean age of 54.7+/-14.2 years and was
      56.7% female. Participants with blood pressure (BP) controlled to JNC 7
      guidelines were more satisfied with their medication than those with uncontrolled
      BP (90.3 vs 71.5%, P<0.05). Patients who had not experienced adverse events had
      higher satisfaction than patients experiencing adverse events (90.9 vs 75.8%,
      P<0.05). The most frequently self-reported adverse events were frequent
      urination, sexual dysfunction, and fatigue ranging from 7.0 to 9.6% across
      classes. The adverse event rates differed by class and were lowest among the
      ARBs. Patients on ARBs were the most likely to have switched from a previous
      antihypertensive class as compared to other classes (57.1% ARBs vs 49.8% ACEIs,
      38.7% diuretics, 36.3% CCBs, and 31.7% BBs). Physician recommendation was the
      most common reason for switching. In conclusion, the ability to effectively treat
      hypertension depends upon a patient's satisfaction with antihypertensive therapy,
      which may be improved by achieving BP control and minimizing the occurrence of
      adverse events.

PMID- 15951741
TI  - Validation of TONOPORT V blood-pressure measuring monitor in adults.
AB  - A new automatic blood-pressure (BP) measuring device TONOPORT V was evaluated
      according to the International Protocol for Validation of Blood Pressure
      Measuring Devices in adults by the European Society of Hypertension. BP values
      measured by the TONOPORT V were compared to BP readings from two independent
      observers. A total of 33 patients (20 males, 13 females) provided systolic and
      diastolic BP readings in the normotensive, borderline hypertensive, and
      hypertensive range. Their age varied between 30 and 83 years, and their arm
      circumference between 23 and 36 cm. The device showed a mean (+/-s.d.) deviation
      from observer measurements of -0.7 (4.6) mmHg for systolic and -0.8 (4.4) mmHg
      for diastolic BP. The accuracy of the device did not vary according to BP values
      or other patient characteristics. The device passed all phases of the protocol
      and can be recommended following the regulation rules of the European Society of
      Hypertension.

PMID- 15951742
TI  - Genome-wide search for sarcoidosis susceptibility genes in African Americans.
AB  - Sarcoidosis, a systemic granulomatous disease of unknown etiology, likely results
      from an environmental insult in a genetically susceptible host. In the US,
      African Americans are more commonly affected with sarcoidosis and suffer greater
      morbidity than Caucasians. We searched for sarcoidosis susceptibility loci by
      conducting a genome-wide, sib pair multipoint linkage analysis in 229 African
      American families ascertained through two or more sibs with a history of
      sarcoidosis. Using the Haseman-Elston regression technique, linkage peaks with P
      values less than 0.05 were identified on chromosomes 1p22, 2p25, 5p15-13, 5q11,
      5q35, 9q34, 11p15 and 20q13 with the most prominent peak at D5S2500 on chromosome
      5q11 (P=0.0005). We found agreement for linkage with the previously reported
      genome scan of a German population at chromosomes 1p and 9q. Based on the
      multiple suggestive regions for linkage found in our study population, it is
      likely that more than one gene influences sarcoidosis susceptibility in African
      Americans. Fine mapping of the linked regions, particularly on chromosome 5q,
      should help to refine linkage signals and guide further sarcoidosis candidate
      gene investigation.

PMID- 15951743
TI  - An animal model for venous thrombosis and spontaneous pulmonary embolism.
AB  - STUDY DESIGN: An animal model. OBJECTIVE: To test the natural sequence of venous
      thrombosis and pulmonary thromboembolism experimentally. SETTING: Veterans
      Administration Hospital, USA. METHOD: In dogs, a venous thrombosis was induced in
      a isolated segment of the internal jugular vein by a 5 min exposure to sodium
      morrhuate and then re-establishing venous patency. A tracer, (125)I human
      fibrinogen, was administered through another vein 1 h prior to the end of each
      experiment when a blood sample, the venous thrombus, and the lungs were removed.
      Thrombi were described by age, weight, histology, and fibrin uptake (thrombus to
      blood radioactivity ratio, g/g). Pulmonary emboli (PE) were identified by
      autoradiography of lung slices or by microscopic examination of lung sections.
      RESULTS: Venous thrombosis developed in all experiments, duration 1-64, median 5
      h (n=12). Histologically, younger thrombi were characterized by platelet
      aggregates surrounded by polymorphonuclear leukocytes (PMN), and uniform fibrin
      deposit; the older thrombi by platelet ghost cells, fewer PMN leukocytes, and
      broken fibrin strands and loops (n=6). Pulmonary thromboemboli were imaged as
      'hot spots' in six of six experiments in which lung slices were autoradiographed
      and were identified microscopically in six of six experiments in which lung
      sections were taken. The number of PE diagnosed microscopically did not correlate
      with the age of the corresponding thrombus but was directly related to fibrin
      uptake (n=5, r=0.99, P<0.01). CONCLUSION: An animal model for venous thrombosis
      that generates pulmonary thromboembolism has been described.

PMID- 15951744
TI  - Fertility following spinal cord injury: a systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To review systematically fertility
      of persons with spinal cord injuries (SCI) and their partners. METHODS: Reports
      from six databases (1966-2003), selected annual proceedings (1997-2002) and
      manufacturer's information were screened against eligibility criteria. Searches
      covered female obstetrical issues, and the efficacy of vibration and
      electroejaculation for males, as well as advanced fertility (AF) treatments for
      partners of SCI males. Data were pooled from case-series reports on SCI males'
      ejaculation, and pregnancies and live births for partners of SCI males. RESULTS:
      In all, 2,127 unique reports were evaluated, of which 66 reports were included.
      No studies investigated fertility in SCI females. Ejaculation interventions in
      the last decade resulted in response rates of 95% (95% confidence intervals (CI)
      91%, 99%), with 100% response rate reported in several recent publications. A
      total of 13 studies (1993-2001) yielded pregnancy rates of 51% (95% CI 42%, 60%)
      in partners of SCI males. Of these, 11 studies (1993-2003) yielded live birth
      rates of 41% (95% CI 33%, 49%). CONCLUSIONS: Fertility of SCI males is
      extensively studied. Semen for fertility purposes can generally be obtained using
      vibration and electroejaculation. AF techniques are increasing pregnancy rates.
      Research is needed to improve sperm quality. Freezing of sperm is unlikely to
      significantly improve fertility rates. Fertility of SCI females is addressed only
      in case reports and opinion articles. The opinion that female fertility is
      unaffected by SCI should be further investigated using appropriate research
      methodology.

PMID- 15951745
TI  - The art and design of genetic screens: mouse.
AB  - Humans are mammals, not bacteria or plants, yeast or nematodes, insects or fish.
      Mice are also mammals, but unlike gorilla and goat, fox and ferret, giraffe and
      jackal, they are suited perfectly to the laboratory environment and genetic
      experimentation. In this review, we will summarize the tools, tricks and
      techniques for executing forward genetic screens in the mouse and argue that this
      approach is now accessible to most biologists, rather than being the sole domain
      of large national facilities and specialized genetics laboratories.

PMID- 15951746
TI  - Genetic links between brain development and brain evolution.
AB  - The most defining biological attribute of Homo sapiens is its enormous brain size
      and accompanying cognitive prowess. How this was achieved by means of genetic
      changes over the course of human evolution has fascinated biologists and the
      general public alike. Recent studies have shown that genes controlling brain
      development - notably those implicated in microcephaly (a congenital defect that
      is characterized by severely reduced brain size) - are favoured targets of
      natural selection during human evolution. We propose that genes that regulate
      brain size during development, such as microcephaly genes, are chief contributors
      in driving the evolutionary enlargement of the human brain. Based on the
      synthesis of recent studies, we propose a general methodological template for the
      genetic analysis of human evolution.

PMID- 15951747
TI  - Circadian rhythms from multiple oscillators: lessons from diverse organisms.
AB  - The organization of biological activities into daily cycles is universal in
      organisms as diverse as cyanobacteria, fungi, algae, plants, flies, birds and
      man. Comparisons of circadian clocks in unicellular and multicellular organisms
      using molecular genetics and genomics have provided new insights into the
      mechanisms and complexity of clock systems. Whereas unicellular organisms require
      stand-alone clocks that can generate 24-hour rhythms for diverse processes,
      organisms with differentiated tissues can partition clock function to generate
      and coordinate different rhythms. In both cases, the temporal coordination of a
      multi-oscillator system is essential for producing robust circadian rhythms of
      gene expression and biological activity.

PMID- 15951750
TI  - Glutamate excitotoxicity in glaucoma: throwing the baby out with the bathwater?

PMID- 15951748
TI  - Production of infectious hepatitis C virus in tissue culture from a cloned viral
      genome.
AB  - Hepatitis C virus (HCV) infection causes chronic liver diseases and is a global
      public health problem. Detailed analyses of HCV have been hampered by the lack of
      viral culture systems. Subgenomic replicons of the JFH1 genotype 2a strain cloned
      from an individual with fulminant hepatitis replicate efficiently in cell
      culture. Here we show that the JFH1 genome replicates efficiently and supports
      secretion of viral particles after transfection into a human hepatoma cell line
      (Huh7). Particles have a density of about 1.15-1.17 g/ml and a spherical
      morphology with an average diameter of about 55 nm. Secreted virus is infectious
      for Huh7 cells and infectivity can be neutralized by CD81-specific antibodies and
      by immunoglobulins from chronically infected individuals. The cell culture
      generated HCV is infectious for chimpanzee. This system provides a powerful tool
      for studying the viral life cycle and developing antiviral strategies.

PMID- 15951751
TI  - 3-Snip punctoplasty.

PMID- 15951752
TI  - Macrophthalmos as a long-term outcome of severe open globe injury.

PMID- 15951754
TI  - Exercise-induced diplopia.

PMID- 15951755
TI  - Mapping of central visual function by microperimetry and autofluorescence in
      patients with Best's vitelliform dystrophy.
AB  - PURPOSE: To evaluate retinal sensitivity and fixation patterns in patients with
      Best's dystrophy by microperimetry (MP) and to correlate the results with static
      perimetry and retinal morphology seen by autofluorescence (AF). METHODS: Central
      10 degrees visual fields in 11 patients with Best's dystrophy (VA: 0.5+/-0.38)
      were recorded by the Octopus M2 TOP program and by MP (MP1, Nidek Technologies).
      AF was recorded by HRA (Heidelberg Engineering). RESULTS: High correlation
      (R=0.75, -0.76, -0.48) was found between static perimetry (MS, MD and CLV
      indices) and MP. Based on MP and AF results, three groups of patients were
      formed. Patients in the first two groups fixated inside the central nonuniform
      hypo- and hyperfluorescent AF ring area, next to relative (Group 1) or absolute
      scotoma (Group 2). Inner parts of the retina close to the fovea were most
      affected, whereas regions closer to the periphery of the 10 degrees visual field
      showed near normal function. As the disease progressed, there was an evident
      shift of fixation to preferential retinal locus (PRL) in eight eyes with visual
      acuity 0.2 or less (Group 3). Fixation shift was superior in four eyes, temporal
      in two eyes, and nasal in two eyes. CONCLUSION: MP enabled a highly sensitive
      topographic monitoring of retinal function, showing central or pericentral
      fixation in the early stages, until loss of central function, in eyes with VA 0.2
      or less, caused evident shift of fixation to PRL. PRL was never situated inside
      the central uniform hypofluorescent area, but corresponded with the
      hyperfluorescent ring seen with AF imaging.

PMID- 15951756
TI  - Refractive lens exchange combined with pars plana vitrectomy to correct high
      myopia.
AB  - PURPOSE: To describe the results of refractive lens exchange (RLE) combined with
      simultaneous pars plana vitrectomy (PPV) in the management of severe myopia.
      METHODS: This retrospective study comprised 14 eyes of eight patients who had RLE
      to treat myopia of -19.0+/-5.4 diopters (D). Phacoemulsification, posterior
      chamber intraocular lens (IOL) implantation, and standard three-port vitrectomy
      were performed. Mean postoperative follow-up time was 30 months (range 12-49).
      RESULTS: The postoperative best-corrected visual acuity (BCVA) was 0.68+/-0.23
      compared to 0.37+/-0.24 preoperatively. There was no postoperative decrease in
      visual acuity in any eye. Mean postoperative spherical equivalent was -0.7 D (+/
      1.6). At 30 months mean follow-up time, the spherical equivalents of nine eyes
      (64.3%) were within +/-1 D of emmetropia. There was no significant change in
      astigmatism due to operative procedures. During the 30 months follow-up period
      three eyes (21.4%) required neodymium : yttrium-aluminium-garnet (Nd : YAG)
      capsulotomy for posterior capsule opacification. No retinal detachments or cases
      of cystoid macular oedema (CME) were observed during the follow-up. CONCLUSION:
      RLE was effective in correcting severe myopia. The simultaneously performed PPV
      may reduce the risk of postoperative retinal detachment. This was a pilot study,
      to draw definitive conclusions a prospective study has to be initiated.

PMID- 15951769
TI  - External defibrillators.

PMID- 15951771
TI  - The Dahl Concept: past, present and future.
AB  - The Dahl appliance was described nearly 30 years ago. This removable metal bite
      platform was used to create inter-occlusal space, in a localised part of the
      mouth, to facilitate the placement of restorations on worn anterior teeth. The
      Dahl concept is traditionally associated with the management of worn teeth.
      However, the same principles can be successfully and safely applied to a variety
      of clinical situations. This has simplified the management of historically
      complex problems. The advantages are the preservation of tooth tissue and the
      long-term benefits that brings. This paper reviews the literature related to the
      Dahl concept and how the concept has developed. There is a discussion regarding
      possible future applications and research.

PMID- 15951772
TI  - Bilateral facial pain from cardiac origin. A case report.
AB  - A case of a 65-year-old female patient is reported. Her chief complaint was
      facial pain, so she sought care from her general dental practitioner for
      evaluation of a suspected temporomandibular disorder, after repeated visits to
      the emergency department due to excruciating facial pain associated with
      exertion. The dental examination revealed an edentulous upper and lower jaw.
      Radiographs of the facial bones revealed no abnormalities. Eventually, she was
      referred for cardiological evaluation, as her pain radiated to the chest and
      there was a medical history of myocardial infarction. Cardiac pain may radiate to
      the face and lead patients to seek dental care. In these settings, dentists may
      contribute to the diagnosis of ischemic heart disease and refer patients for
      cardiological evaluation.

PMID- 15951773
TI  - Oral cancer: delays in referral and diagnosis persist.
AB  - Oral cancer accounts for around 1% of all new cancers diagnosed in the United
      Kingdom every year. Mortality rates remain relatively high and prognosis is worst
      in cases of more advanced disease at time of diagnosis. Early identification of
      malignant lesions and speedy referral to a specialist for treatment are therefore
      important. The reasons and extent of the delays at the different stages between a
      patient first noticing an oral lesion and attending a health care professional
      and then being referred for specialist care have previously been studied and
      consistently found to be longer than desired. The National Oral Cancer Awareness
      Week (NOCAW), first run in 1995, aimed to increase the awareness of oral cancer
      amongst health care professionals and the public. It has since been repeated and
      is now an annual event. Alongside publications by the British Dental Association
      and guidelines circulated by the Department of Health on oral cancer diagnosis
      and referral, it is hoped this will lead to a decrease in the delay between the
      onset of oral cancer and patients receiving appropriate treatment. We looked at
      the previously published data on referral delay in oral cancer both in the United
      Kingdom and overseas and then identified delays in referral of oral cancer
      patients in a region that had been studied before NOCAW was introduced, to see if
      this was having any effect on referral delays. We found that despite the great
      publicity raised by NOCAW and the other publications and courses on oral cancer
      since the original audit, patient delay and referral delay have not improved. We
      conclude that more needs to be done to transfer guidelines to everyday practice.

PMID- 15951774
TI  - Complications following replantation of a primary incisor: a cautionary tale.
AB  - The replantation of avulsed primary incisors is contra-indicated. This case
      describes an 8-year-old child who six years previously had avulsed and had
      replanted a primary central incisor. At presentation, this tooth was retained,
      the permanent successor had failed to erupt and appearance of the adjacent
      lateral incisor was notably delayed. Investigation revealed a radicular cyst in
      relation to the replanted deciduous incisor together with severe displacement of
      the permanent tooth, which could not be saved.

PMID- 15951782
TI  - Irradiated jaws.

PMID- 15951783
TI  - Scientific basis.

PMID- 15951784
TI  - Patient perception.

PMID- 15951785
TI  - An assessment of career satisfaction among a group of general dental
      practitioners in Staffordshire.
AB  - OBJECTIVES: To assess the level of job satisfaction among general dental
      practitioners from one area of England, and to assess the association of various
      personal and work related factors with job satisfaction. DESIGN: Postal
      questionnaire survey. SETTING: General dental practices in South Staffordshire,
      Wolverhampton and Dudley, England. METHOD: An anonymous questionnaire posted to
      all 396 registered dentists in the above areas. RESULTS: A 75% response rate was
      achieved. Data were analysed using non-parametric statistics for any significant
      differences in the scores for stress, respect, overall professional satisfaction,
      quality of life and overall job satisfaction according to the different
      demographic groupings of the dentists (alpha =0.05). Dentists with an area of
      special interest had higher scores in all categories except quality of life.
      Overall job satisfaction was higher among private dentists, and those in group
      practices and in non-rural locations. The highest bi-variate correlation occurred
      between overall job satisfaction and overall professional satisfaction, delivery
      of care, income, respect and professional time. CONCLUSIONS: Job satisfaction was
      judged to be good among this group. Stress was the factor associated with the
      greatest dissatisfaction. This survey produced similar results to preceding US
      studies, and suggests ways of improving job satisfaction.

PMID- 15951786
TI  - Comparative study of two canal obturation techniques by image analysis and EDS
      microanalysis.
AB  - AIM: The aim of this in vitro study was to compare the marginal adaptation
      achieved by two obturation techniques (lateral condensation and Thermafil) using
      human teeth prepared by continuous rotation with the HERO 642(R) system. METHOD:
      The percentages of gaps and sealer on the root canal surface were determined by
      analysing the images of 12 sections per tooth. Tubule sealer penetration was
      assessed by backscattered scanning electron microscopy and energy dispersive
      spectrometry microanalysis. RESULTS: The Thermafil obturation technique resulted
      in virtually no gaps and very low amounts of sealer on the root surface, unlike
      the lateral condensation technique. Tubule sealer penetration occurred with both
      techniques, but was deeper, especially in the mid and apical zones, with the
      lateral condensation technique.

PMID- 15951787
TI  - A survey of dental school applicants' career intentions and the balance with
      family life.
AB  - PURPOSE: To investigate the career plans of prospective dental students and how
      they foresee their work life balance. METHOD: Applicants to Dundee and Manchester
      dental schools completed anonymous questionnaires when they attended for
      interview. RESULTS: The useable response rate was 94% (n=436). The majority of
      the respondents (91.3%) intended working full time when they enter the workforce,
      with no significant variation detected between males and females. The cohort
      anticipated their mean salary to be just over 28,000 UK pounds, five years into
      their career, although the males felt they would be earning 5,000 UK pounds more
      than the females. Individuals of Pakistani and Indian origin thought they would
      earn most, and Asians least. Sixty-five per cent would enter general dental
      practice and, of these, only 2.8% expected to work exclusively within the NHS.
      Fifteen per cent intended to go into the hospital dental service, with
      orthodontics the most popular choice of subspecialty (43.7%), followed by oral
      surgery (31.1%). Significant variation was seen between ethnic groups, with the
      hospital and community dental services being more popular with those who
      identified themselves as of non-white ethnic origin, although the majority would
      still plan on entering general dental practice. Almost half (44.5%) would take
      time out of their career to concentrate on childcare when children were of pre
      school age, with a further 11% taking longer. Ninety per cent of females and 70%
      of males anticipated taking time out, of a varying duration. Half of the
      respondents indicated that they felt a child would affect their career to a
      moderate extent. CONCLUSIONS: The dental profession will be severely affected if
      both males and females take time out of their careers in the future. As well as a
      work force shortage, the problems of accessibility to NHS dental services will be
      exacerbated if fewer dentists choose to provide NHS care.

PMID- 15951802
TI  - Serum response factor regulates a muscle-specific microRNA that targets Hand2
      during cardiogenesis.
AB  - Gradients of signalling and transcription factors govern many aspects of
      embryogenesis, highlighting the need for spatiotemporal control of regulatory
      protein levels. MicroRNAs are phylogenetically conserved small RNAs that regulate
      the translation of target messenger RNAs, providing a mechanism for protein dose
      regulation. Here we show that microRNA-1-1 (miR-1-1) and miR-1-2 are specifically
      expressed in cardiac and skeletal muscle precursor cells. We found that the miR-1
      genes are direct transcriptional targets of muscle differentiation regulators
      including serum response factor, MyoD and Mef2. Correspondingly, excess miR-1 in
      the developing heart leads to a decreased pool of proliferating ventricular
      cardiomyocytes. Using a new algorithm for microRNA target identification that
      incorporates features of RNA structure and target accessibility, we show that
      Hand2, a transcription factor that promotes ventricular cardiomyocyte expansion,
      is a target of miR-1. This work suggests that miR-1 genes titrate the effects of
      critical cardiac regulatory proteins to control the balance between
      differentiation and proliferation during cardiogenesis.

PMID- 15951803
TI  - Fruit-specific RNAi-mediated suppression of DET1 enhances carotenoid and
      flavonoid content in tomatoes.
AB  - Tomatoes are a principal dietary source of carotenoids and flavonoids, both of
      which are highly beneficial for human health. Overexpression of genes encoding
      biosynthetic enzymes or transcription factors have resulted in tomatoes with
      improved carotenoid or flavonoid content, but never with both. We attempted to
      increase tomato fruit nutritional value by suppressing an endogenous
      photomorphogenesis regulatory gene, DET1, using fruit-specific promoters combined
      with RNA interference (RNAi) technology. Molecular analysis indicated that DET1
      transcripts were indeed specifically degraded in transgenic fruits. Both
      carotenoid and flavonoid contents were increased significantly, whereas other
      parameters of fruit quality were largely unchanged. These results demonstrate
      that manipulation of a plant regulatory gene can simultaneously influence the
      production of several phytonutrients generated from independent biosynthetic
      pathways, and provide a novel example of the use of organ-specific gene silencing
      to improve the nutritional value of plant-derived products.

PMID- 15951804
TI  - Stepwise engineering to produce high yields of very long-chain polyunsaturated
      fatty acids in plants.
AB  - Very long chain polyunsaturated fatty acids (VLCPUFAs) such as arachidonic acid
      (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are valuable
      commodities that provide important human health benefits. We report the
      transgenic production of significant amounts of AA and EPA in Brassica juncea
      seeds via a stepwise metabolic engineering strategy. Using a series of
      transformations with increasing numbers of transgenes, we demonstrate the
      incremental production of VLCPUFAs, achieving AA levels of up to 25% and EPA
      levels of up to 15% of total seed fatty acids. Both fatty acids were almost
      exclusively found in triacylglycerols, with AA located preferentially at sn-2 and
      sn-3 positions and EPA distributed almost equally at all three positions.
      Moreover, we reconstituted the DHA biosynthetic pathway in plant seeds,
      demonstrating the practical feasibility of large-scale production of this
      important omega-3 fatty acid in oilseed crops.

PMID- 15951805
TI  - Multiplexed detection of pathogen DNA with DNA-based fluorescence nanobarcodes.
AB  - Rapid, multiplexed, sensitive and specific molecular detection is of great demand
      in gene profiling, drug screening, clinical diagnostics and environmental
      analysis. One of the major challenges in multiplexed analysis is to identify each
      specific reaction with a distinct label or 'code'. Two encoding strategies are
      currently used: positional encoding, in which every potential reaction is
      preassigned a particular position on a solid-phase support such as a DNA
      microarray, and reaction encoding, where every possible reaction is uniquely
      tagged with a code that is most often optical or particle based. The micrometer
      size, polydispersity, complex fabrication process and nonbiocompatibility of
      current codes limit their usability. Here we demonstrate the synthesis of
      dendrimer-like DNA-based, fluorescence-intensity-coded nanobarcodes, which
      contain a built-in code and a probe for molecular recognition. Their application
      to multiplexed detection of the DNA of several pathogens is first shown using
      fluorescence microscopy and dot blotting, and further demonstrated using flow
      cytometry that resulted in detection that was sensitive (attomole) and rapid.

PMID- 15951806
TI  - Endosome-to-cytosol transport of viral nucleocapsids.
AB  - During viral infection, fusion of the viral envelope with endosomal membranes and
      nucleocapsid release were thought to be concomitant events. We show here that for
      the vesicular stomatitis virus they occur sequentially, at two successive steps
      of the endocytic pathway. Fusion already occurs in transport intermediates
      between early and late endosomes, presumably releasing the nucleocapsid within
      the lumen of intra-endosomal vesicles, where it remains hidden. Transport to late
      endosomes is then required for the nucleocapsid to be delivered to the cytoplasm.
      This last step, which initiates infection, depends on the late endosomal lipid
      lysobisphosphatidic acid (LBPA) and its putative effector Alix/AIP1, and is
      regulated by phosphatidylinositol-3-phosphate (PtdIns3P) signalling via the
      PtdIns3P-binding protein Snx16. We conclude that the nucleocapsid is exported
      into the cytoplasm after the back-fusion of internal vesicles with the limiting
      membrane of late endosomes, and that this process is controlled by the
      phospholipids LBPA and PtdIns3P and their effectors.

PMID- 15951808
TI  - Preferring one taste over another without recognizing either.
AB  - Stimuli can be discriminated without being consciously perceived and can be
      preferred without being remembered. Here we report a subject with a previously
      unknown dissociation of abilities: a strong behavioral preference for the taste
      of sugar over saline, despite a complete failure of recognition. The pattern of
      brain damage responsible for the dissociation suggests that reliable behavioral
      choice among tastes can occur in the absence of the gustatory cortex necessary
      for taste recognition.

PMID- 15951807
TI  - S-nitrosylated GAPDH initiates apoptotic cell death by nuclear translocation
      following Siah1 binding.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) influences cytotoxicity,
      translocating to the nucleus during apoptosis. Here we report a signalling
      pathway in which nitric oxide (NO) generation that follows apoptotic stimulation
      elicits S-nitrosylation of GAPDH, which triggers binding to Siah1 (an E3
      ubiquitin ligase), nuclear translocation and apoptosis. S-nitrosylation of GAPDH
      augments its binding to Siah1, whose nuclear localization signal mediates
      translocation of GAPDH. GAPDH stabilizes Siah1, facilitating its degradation of
      nuclear proteins. Activation of macrophages by endotoxin and of neurons by
      glutamate elicits GAPDH-Siah1 binding, nuclear translocation and apoptosis, which
      are prevented by NO deletion. The NO-S-nitrosylation-GAPDH-Siah1 cascade may
      represent an important molecular mechanism of cytotoxicity.

PMID- 15951809
TI  - Dynamic mobility of functional GABAA receptors at inhibitory synapses.
AB  - Importing functional GABAA receptors into synapses is fundamental for
      establishing and maintaining inhibitory transmission and for controlling neuronal
      excitability. By introducing a binding site for an irreversible inhibitor into
      the GABAA receptor alpha1 subunit channel lining region that can be accessed only
      when the receptor is activated, we have determined the dynamics of receptor
      mobility between synaptic and extrasynaptic locations in hippocampal pyramidal
      neurons. We demonstrate that the cell surface GABAA receptor population shows no
      fast recovery after irreversible inhibition. In contrast, after selective
      inhibition, the synaptic receptor population rapidly recovers by the import of
      new functional entities within minutes. The trafficking pathways that promote
      rapid importation of synaptic receptors do not involve insertion from
      intracellular pools, but reflect receptor diffusion within the plane of the
      membrane. This process offers the synapse a rapid mechanism to replenish
      functional GABAA receptors at inhibitory synapses and a means to control synaptic
      efficacy.

PMID- 15951810
TI  - Reference frames for representing visual and tactile locations in parietal
      cortex.
AB  - The ventral intraparietal area (VIP) receives converging inputs from visual,
      somatosensory, auditory and vestibular systems that use diverse reference frames
      to encode sensory information. A key issue is how VIP combines those inputs
      together. We mapped the visual and tactile receptive fields of multimodal VIP
      neurons in macaque monkeys trained to gaze at three different stationary targets.
      Tactile receptive fields were found to be encoded into a single somatotopic, or
      head-centered, reference frame, whereas visual receptive fields were widely
      distributed between eye- to head-centered coordinates. These findings are
      inconsistent with a remapping of all sensory modalities in a common frame of
      reference. Instead, they support an alternative model of multisensory integration
      based on multidirectional sensory predictions (such as predicting the location of
      a visual stimulus given where it is felt on the skin and vice versa). This
      approach can also explain related findings in other multimodal areas.

PMID- 15951811
TI  - Neuronal fate determinants of adult olfactory bulb neurogenesis.
AB  - Adult neurogenesis in mammals is restricted to two small regions, including the
      olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated
      throughout the entire lifespan. However, the mechanisms directing them towards a
      specific neuronal phenotype are not yet understood. Here, we demonstrate the dual
      role of the transcription factor Pax6 in generating neuronal progenitors and also
      in directing them towards a dopaminergic periglomerular phenotype in adult mice.
      We present further evidence that dopaminergic periglomerular neurons originate in
      a distinct niche, the rostral migratory stream, and are fewer derived from
      precursors in the zone lining the ventricle. This regionalization of the adult
      precursor cells is further supported by the restricted expression of the
      transcription factor Olig2, which specifies transit-amplifying precursor fate and
      opposes the neurogenic role of Pax6. Together, these data explain both extrinsic
      and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.

PMID- 15951812
TI  - Requirement for Notch1 signals at sequential early stages of intrathymic T cell
      development.
AB  - Signaling through the transmembrane Notch1 receptor directs thymus-seeding
      progenitors (TSPs) to suppress their B cell potential and 'choose' the T cell
      fate. Present paradigms suggest that TSPs are contained in the multipotent early
      T lineage precursor (ETP) subset of thymocytes. However, we show here that the B
      cell potential of ETPs was not augmented in microenvironments that limited Notch1
      activation. Furthermore, low-threshold Notch1 signals suppressed B cell
      production by TSPs before they reached the ETP stage. Notch1 signals of a higher
      threshold were needed to drive proliferation of ETPs and development into
      CD4(+)CD8(+) double-positive thymocytes. Thus, TSPs can be differentiated from
      all previously identified early T cell progenitors by their robust B cell
      potential and exquisite sensitivity to Notch1 signals.

PMID- 15951813
TI  - Notch signaling controls the generation and differentiation of early T lineage
      progenitors.
AB  - Signaling by the transmembrane receptor Notch is critical for T lineage
      development, but progenitor subsets that first receive Notch signals have not
      been defined. Here we identify an immature subset of early T lineage progenitors
      (ETPs) in the thymus that expressed the tyrosine kinase receptor Flt3 and had
      preserved B lineage potential at low progenitor frequency. Notch signaling was
      active in ETPs and was required for generation of the ETP population.
      Additionally, Notch signals contributed to the subsequent differentiation of
      ETPs. In contrast, multipotent hematopoietic progenitors circulated in the blood
      even in the absence of Notch signaling, suggesting that critical Notch signals
      during early T lineage development are delivered early after thymic entry.

PMID- 15951814
TI  - A critical function for type I interferons in cancer immunoediting.
AB  - 'Cancer immunoediting' is a process wherein the immune system protects hosts
      against tumor development and facilitates outgrowth of tumors with reduced
      immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in
      this process, the involvement of type I interferons (IFN-alpha/beta) has not been
      elucidated. We now show that, like IFN-gamma, endogenously produced IFN
      alpha/beta was required for the prevention of the growth of primary carcinogen
      induced and transplantable tumors. Although tumor cells are important IFN-gamma
      targets, they are not functionally relevant sites of the actions of the type I
      interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta
      targets during development of protective antitumor responses. Therefore, type I
      interferons are important components of the cancer immunoediting process and
      function in a way that does not completely overlap the functions of IFN-gamma.

PMID- 15951815
TI  - Alternating sequence of ring and chain structures in sulphur at high pressure and
      temperature.
AB  - Sulphur is the subject of a renewed intensive research effort aiming at
      characterizing its complex phase diagram. Nonetheless, on reading recent
      literature on its high-pressure phases, a confused picture emerges where
      different techniques obtain different results. We have investigated the phase
      diagram of sulphur by X-ray diffraction at high pressures and temperatures (6-11
      GPa and 300-1,000 K), and have observed a new occurrence of a molecular S6 phase,
      in addition to the previously described polymeric helical trigonal and tetragonal
      phases. The stability regime of the S6 phase has been defined through the
      observation of coexistence points with each of the polymeric phases and the
      trigonal-S6-tetragonal triple point. The existence of these high-pressure phases
      allows us to define a framework that reconciles the apparently contradictory
      results existing in the literature. Moreover, the classic idea that pressure
      induces polymerization in sulphur is refined by the direct observation of an
      alternating sequence of molecular and polymeric phases that we report here.

PMID- 15951816
TI  - Multifunctional brushes made from carbon nanotubes.
AB  - Brushes are common tools for use in industry and our daily life, performing a
      variety of tasks such as cleaning, scraping, applying and electrical contacts.
      Typical materials for constructing brush bristles include animal hairs, synthetic
      polymer fibres and metal wires (see, for example, ref. 1). The performance of
      these bristles has been limited by the oxidation and degradation of metal wires,
      poor strength of natural hairs, and low thermal stability of synthetic fibres.
      Carbon nanotubes, having a typical one-dimensional nanostructure, have excellent
      mechanical properties, such as high modulus and strength, high elasticity and
      resilience, thermal conductivity and large surface area (50-200 m2 g(-1)). Here
      we construct multifunctional, conductive brushes with carbon nanotube bristles
      grafted on fibre handles, and demonstrate their several unique tasks such as
      cleaning of nanoparticles from narrow spaces, coating of the inside of holes,
      selective chemical adsorption, and as movable electromechanical brush contacts
      and switches. The nanotube bristles can also be chemically functionalized for
      selective removal of heavy metal ions.

PMID- 15951817
TI  - The archaeal exosome core is a hexameric ring structure with three catalytic
      subunits.
AB  - The exosome is a 3' --> 5' exoribonuclease complex involved in RNA processing. We
      report the crystal structure of the RNase PH core complex of the Sulfolobus
      solfataricus exosome determined at a resolution of 2.8 A. The structure reveals a
      hexameric ring-like arrangement of three Rrp41-Rrp42 heterodimers, where both
      subunits adopt the RNase PH fold common to phosphorolytic exoribonucleases.
      Structure-guided mutagenesis reveals that the activity of the complex resides
      within the active sites of the Rrp41 subunits, all three of which face the same
      side of the hexameric structure. The Rrp42 subunit is inactive but contributes to
      the structuring of the Rrp41 active site. The high sequence similarity of this
      archaeal exosome to eukaryotic exosomes and its high structural similarity to the
      bacterial mRNA-degrading PNPase support a common basis for RNA-degrading
      machineries in all three domains of life.

PMID- 15951818
TI  - Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex
      with an alpha-conotoxin PnIA variant.
AB  - Conotoxins (Ctx) form a large family of peptide toxins from cone snail venoms
      that act on a broad spectrum of ion channels and receptors. The subgroup alpha
      Ctx specifically and selectively binds to subtypes of nicotinic acetylcholine
      receptors (nAChRs), which are targets for treatment of several neurological
      disorders. Here we present the structure at a resolution of 2.4 A of alpha-Ctx
      PnIA (A10L D14K), a potent blocker of the alpha(7)-nAChR, bound with high
      affinity to acetylcholine binding protein (AChBP), the prototype for the ligand
      binding domains of the nAChR superfamily. Alpha-Ctx is buried deep within the
      ligand-binding site and interacts with residues on both faces of adjacent
      subunits. The toxin itself does not change conformation, but displaces the C loop
      of AChBP and induces a rigid-body subunit movement. Knowledge of these contacts
      could facilitate the rational design of drug leads using the Ctx framework and
      may lead to compounds with increased receptor subtype selectivity.

PMID- 15951819
TI  - Structural dissection and high-throughput screening of mannosylglycerate
      synthase.
AB  - The enzymatic transfer of activated mannose yields mannosides in glycoconjugates
      and oligo- and polysaccharides. Yet, despite its biological necessity, the
      mechanism by which glycosyltransferases recognize mannose and catalyze its
      transfer to acceptor molecules is poorly understood. Here, we report broad high
      throughput screening and kinetic analyses of both natural and synthetic
      substrates of Rhodothermus marinus mannosylglycerate synthase (MGS), which
      catalyzes the formation of the stress protectant 2-O-alpha-D-mannosyl glycerate.
      The sequence of MGS indicates that it is at the cusp of inverting and retaining
      transferases. The structures of apo MGS and complexes with donor and acceptor
      molecules, including GDP-mannose, combined with mutagenesis of the binding and
      catalytic sites, unveil the mannosyl transfer center. Nucleotide specificity is
      as important in GDP-D-mannose recognition as the nature of the donor sugar.

PMID- 15951820
TI  - The roles of MAD1, MAD2 and MAD3 in meiotic progression and the segregation of
      nonexchange chromosomes.
AB  - Errors in meiotic chromosome segregation are the leading cause of spontaneous
      abortions and birth defects. In humans, chromosomes that fail to experience
      crossovers (or exchanges) are error-prone, more likely than exchange chromosomes
      to mis-segregate in meiosis. We used a yeast model to investigate the mechanisms
      that partition nonexchange chromosomes. These studies showed that the spindle
      checkpoint genes MAD1, MAD2 and MAD3 have different roles. We identified a new
      meiotic role for MAD3; though dispensable for the segregation of exchange
      chromosomes, it is essential for the segregation of nonexchange chromosomes. This
      function of Mad3p could also be carried out by human BubR1. MAD1 and MAD2 act in
      a surveillance mechanism that mediates a metaphase delay in response to
      nonexchange chromosomes, whereas MAD3 acts as a crucial meiotic timer, mediating
      a prophase delay in every meiosis. These findings suggest plausible models for
      the basis of errant meiotic segregation in humans.

PMID- 15951821
TI  - Use of human tissue to assess the oncogenic activity of melanoma-associated
      mutations.
AB  - Multiple genetic alterations occur in melanoma, a lethal skin malignancy of
      increasing incidence. These include mutations that activate Ras and two of its
      effector cascades, Raf and phosphoinositide 3-kinase (PI3K). Induction of Ras and
      Raf can be caused by active N-Ras and B-Raf mutants as well as by gene
      amplification. Activation of PI3K pathway components occurs by PTEN loss and by
      AKT3 amplification. Melanomas also commonly show impairment of the p16(INK4A)
      CDK4-Rb and ARF-HDM2-p53 tumor suppressor pathways. CDKN2A mutations can produce
      p16(INK4A) and ARF protein loss. Rb bypass can also occur through activating CDK4
      mutations as well as by CDK4 amplification. In addition to ARF deletion, p53
      pathway disruption can result from dominant negative TP53 mutations. TERT
      amplification also occurs in melanoma. The extent to which these mutations can
      induce human melanocytic neoplasia is unknown. Here we characterize pathways
      sufficient to generate human melanocytic neoplasia and show that genetically
      altered human tissue facilitates functional analysis of mutations observed in
      human tumors.

PMID- 15951822
TI  - Birth of a metabolic gene cluster in yeast by adaptive gene relocation.
AB  - Although most eukaryotic genomes lack operons, they contain some physical
      clusters of genes that are related in function despite being unrelated in
      sequence. How these clusters are formed during evolution is unknown. The DAL
      cluster is the largest metabolic gene cluster in yeast and consists of six
      adjacent genes encoding proteins that enable Saccharomyces cerevisiae to use
      allantoin as a nitrogen source. We show here that the DAL cluster was assembled,
      quite recently in evolutionary terms, through a set of genomic rearrangements
      that happened almost simultaneously. Six of the eight genes involved in allantoin
      degradation, which were previously scattered around the genome, became relocated
      to a single subtelomeric site in an ancestor of S. cerevisiae and Saccharomyces
      castellii. These genomic rearrangements coincided with a biochemical
      reorganization of the purine degradation pathway, which switched to importing
      allantoin instead of urate. This change eliminated urate oxidase, one of several
      oxygen-consuming enzymes that were lost by yeasts that can grow vigorously in
      anaerobic conditions. The DAL cluster is located in a domain of modified
      chromatin involving both H2A.Z histone exchange and Hst1-Sum1-mediated histone
      deacetylation, and it may be a coadapted gene complex formed by epistatic
      selection.

PMID- 15951823
TI  - Smallpox vaccine-induced antibodies are necessary and sufficient for protection
      against monkeypox virus.
AB  - Vaccination with live vaccinia virus affords long-lasting protection against
      variola virus, the agent of smallpox. Its mode of protection in humans, however,
      has not been clearly defined. Here we report that vaccinia-specific B-cell
      responses are essential for protection of macaques from monkeypox virus, a
      variola virus ortholog. Antibody-mediated depletion of B cells, but not CD4+ or
      CD8+ T cells, abrogated vaccine-induced protection from a lethal intravenous
      challenge with monkeypox virus. In addition, passive transfer of human vaccinia
      neutralizing antibodies protected nonimmunized macaques from severe disease.
      Thus, vaccines able to induce long-lasting protective antibody responses may
      constitute realistic alternatives to the currently available smallpox vaccine
      (Dryvax).

PMID- 15951824
TI  - Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell
      vaccination.
AB  - Efficient boosting of memory T-cell numbers to protective levels generally
      requires a relatively long interval between immunizations. Decreasing this
      interval could be crucial in biodefense and cancer immunotherapy, in which rapid
      protective responses are essential. Here, we show that vaccination with peptide
      coated dendritic cells (DCs) generated CD8+ T cells with the phenotype and
      function of memory cells within 4-6 d. These early memory CD8+ T cells underwent
      vigorous secondary expansion in response to a variety of booster immunizations,
      leading to elevated numbers of effector and memory T cells and enhanced
      protective immunity. Coinjection of CpG oligodeoxynucleotides, potent inducers of
      inflammation that did not alter the duration of DC antigen display, prevented the
      rapid generation of memory T cells in wild-type mice but not in mice lacking the
      interferon (IFN)-gamma receptor. These data show that DC vaccination stimulates a
      pathway of accelerated generation of memory T cells, and suggest that events of
      inflammation, including the action of IFN-gamma on the responding T cells,
      control the rate of development of memory CD8+ T cells.

PMID- 15951826
TI  - Intrinsic inhibitory innervation of the stomach.

PMID- 15951827
TI  - Thrombin-induced glucose transport via Src-p38 MAPK pathway in vascular smooth
      muscle cells.
AB  - Thrombin is a mitogen for vascular smooth muscle cells (VSMC) and has been
      implicated in the development in atherosclerosis. However, little is known about
      the role of thrombin in glucose transport in VSMC. In this study, we examined the
      effect of thrombin on glucose uptake in rat A10 VSMC. We found that thrombin
      induced glucose uptake in a dose-dependent manner while hirudin, a potent
      thrombin inhibitor, prevented glucose uptake in the cells. PP2, a selective
      inhibitor of Src, prevented the thrombin-induced glucose uptake, but did not
      affect insulin-induced uptake. We also examined whether mitogen-activated protein
      kinase (MAPK) inhibitors influenced thrombin-induced glucose uptake. The p38 MAPK
      inhibitor (SB203580) inhibited thrombin-induced glucose uptake, but the MEK
      inhibitor (PD98059) did not. In contrast to thrombin, SB203580 did not affect
      insulin-induced glucose uptake. Furthermore, thrombin failed to translocate the
      insulin-sensitive glucose transporter GLUT4. These findings suggest that thrombin
      stimulates glucose transport via Src and subsequent p38 MAPK activation in VSMC.

PMID- 15951828
TI  - Dual regulation of myofilament Ca2+ sensitivity by levosimendan in normal and
      acidotic conditions in aequorin-loaded canine ventricular myocardium.
AB  - Experiments were carried out in canine ventricular trabeculae loaded with
      aequorin to investigate the effects of levosimendan {(R)-([4-(1,4,5,6-tetrahydro
      4-methyl-6-oxo-3-pyridazinyl)phenyl]-hydrazono)-propanedinitrile} on contractile
      force and Ca(2+) transients in normal and acidotic conditions. The concentration
      response curve for the positive inotropic effect (PIE) of levosimendan was bell
      shaped, that is, it declined markedly at 10(-4) M after achieving the maximum at
      10(-5) M in normal (pH(o)=7.4) and acidotic conditions (pH(o)=6.6). The positive
      inotropic effect (PIE) of levosimendan up to 10(-5) M was associated with an
      increase in Ca(2+) transients and a shift of the relationship of Ca(2+)
      transients and force to the left of that of elevation of [Ca(2+)](o).
      Levosimendan at 10(-4) M elicited a negative inotropic effect (NIE) in
      association with a further increase in Ca(2+) transients, and during washout
      Ca(2+) transients increased further, while the force was abolished before both
      signals recovered to the control. In acidotic conditions, the relationship of
      Ca(2+) transients and force during the application of levosimendan in normal
      conditions was essentially unaltered, whereas the PIE was suppressed due to
      attenuation of the increase in Ca(2+) transients. In summary, in intact canine
      ventricular myocardium, levosimendan elicits a dual inotropic effect: at lower
      concentrations, it induces a PIE by a combination of increases in Ca(2+)
      transients and Ca(2+) sensitivity, while at higher concentrations it elicits an
      NIE due to a decrease in Ca(2+) sensitivity. Acidosis inhibits the PIE of
      levosimendan due to suppression of the increase in Ca(2+) transients in response
      to the compound.

PMID- 15951829
TI  - Amiloride protects against pentylenetetrazole-induced kindling in mice.
AB  - This study was performed to investigate whether or not amiloride, a sodium
      hydrogen exchanger (NHE) inhibitor, can protect against seizure development of
      pentylenetetrazole (PTZ)-induced kindling in mice.Kindling was induced by once
      every 2 days treatment with PTZ (25 mg kg(-1) i.p.) for 5 weeks. Challenge
      experiments were carried out after 15 or 30 days of last treatment with PTZ.
      Administration of amiloride (2 h before PTZ, in doses of 0.65 and 1.3 mg kg(-1),
      p.o.) significantly prolonged the onset of kindling and reduced the incidence and
      severity of seizures in a dose-dependent manner. The effect of amiloride on the
      incidence of PTZ-induced seizures was evident even after 15 or 30 days of last
      treatment. The results indicate a protective role for amiloride against PTZ
      induced kindling in mice. The possibility of mediation of such effects by NHE
      inhibition is discussed.

PMID- 15951830
TI  - Effect of oral administration of zanapezil (TAK-147) for 21 days on acetylcholine
      and monoamines levels in the ventral hippocampus of freely moving rats.
AB  - Zanapezil (TAK-147 (3-[1benzylpiperdin-4-yl]-1-(2,3,4,5-tetrahydro-1 H-1
      benzazepin-8-yl) propan-1-one fumarate)) is a selective acetylcholine (ACh)
      esterase inhibitor under investigation as a drug for Alzheimer's disease (AD)
      treatment. In this study, the effects of TAK-147 at 2 mg kg(-1) p.o. for 21 days,
      compared to donepezil (E2020), on the levels of ACh, catecolamines and
      indoleamines were investigated in the ventral hippocampus (VH) of freely moving
      rats by microdialysis-high-performance liquid chromatography. The results
      revealed that the VH contains 92.05+/-21.97 fmol 20 microl(-1) ACh and the
      following monoamines levels (pg 30 microl(-1)), norepinephrine (NE) 1.92+/-0.39,
      epinephrine (Epi) 1.91+/-0.183, 3-methoxy-4-hydroxyphenylglycol (MHPG) 11.53+/
      3.22, normetanephrine 3.26+/-0.61, dopamine (DA) 0.77+/-0.23, 3,4
      dihydroxyphenylacetic acid (DOPAC) 3.37+/-1.01, homovanillic acid (4-hydroxy-3
      methoxyphenylacetic acid; HVA) 4.04+/-0.93, 3-methoxytyramine 0.64+/-0.13,
      serotonin (5-HT) 0.73+/-0.16 and 5-hydroxyindoleacetic acid (5-HIAA) 313.15+/
      18.42. On the 21st day and prior to the last dose, TAK-147 increased ACh, Epi, DA
      and 5-HT, whereas E2020 increased MHPG, Epi and DA. Following the last dose, TAK
      147 increased NE, whereas E2020 increased NE, ACh and 5-HT in addition to their
      effects prior to the last dose. TAK-147 decreased HVA : DA ratio, but only
      marginally decreased DOPAC : DA and 5-HIAA : 5-HT ratios. On the other hand,
      E2020 decreased ratios of HVA : DA, DOPAC : DA (prior to the last dose), and 5
      HIAA : 5-HT (90-180 min after the last dose). Both drugs decreased MHPG : NE only
      at 180 min after the last dose. The results also showed that TAK-147 increased
      Epi : NE ratio prior to and for 120 min following the last dose, whereas E2020
      increased the ratio only before the last dose. The present results show that TAK
      147 at a subthreshold dose could differentially increase ACh and 5-HT, compared
      to MHPG increased by E2020. The last dose of each drug could extend their effects
      to other monoamines. The increase of the monoamines levels, in addition to that
      on the ACh, and decrease of their oxidation could be of value in the treatment of
      the AD, other dementic diseases and the cohort neurological disorders depending
      on the type of the monoamine underlying the disorder.

PMID- 15951831
TI  - APT070 (Mirococept), a membrane-localised complement inhibitor, inhibits
      inflammatory responses that follow intestinal ischaemia and reperfusion injury.
AB  - Activation of the complement system has been shown to play a major role in the
      mediation of reperfusion injury. Here, we assessed the effects of APT070
      (Mirococept), a novel membrane-localised complement inhibitor based on a
      recombinant fragment of soluble CR1, on the local, remote and systemic injuries
      following intestinal ischaemia and reperfusion (I/R) in the rat. In a model of
      mild I/R injury (30 min of ischaemia and 30 min of reperfusion), APT070 dose
      dependently (1-10 mg kg(-1)) inhibited the increase in vascular permeability of
      and neutrophil influx into intestine and lungs. Maximal inhibition occurred at 10
      mg kg(-1). Following severe I/R injury (120 min of ischaemia and 120 min of
      reperfusion), APT070 (10 mg kg(-1)) markedly prevented neutrophil influx and the
      increase in vascular permeability both in the intestine and the lungs.APT070 also
      effectively suppressed the increase of tissue (intestine and lungs) and serum
      concentrations of TNF-alpha and IL-6, but not those of IL-1beta or IL-10. There
      was no significant reduction of mortality in the APT070 group. In conclusion,
      treatment with the membrane-targeted complement inhibitor APT070 significantly
      reduced the hyperinflammatory response after mild and severe ischaemia and
      reperfusion injury (I/RI) in rats. APT070 may be effective in therapeutic
      indications involving gut I/RI.

PMID- 15951832
TI  - New positron emission tomography tracer [(11)C]carvedilol reveals P-glycoprotein
      modulation kinetics.
AB  - Imaging of P-glycoprotein (P-gp) function in the blood-brain barrier (BBB) may
      support development of strategies, which will improve drug delivery to the brain.
      [(11)C]verapamil has been developed as a positron emission tomography (PET)
      tracer, to image P-gp function in vivo. Ideally, for the purpose of brain
      imaging, tracers should have a log P between 0.9 and 2.5. The beta-receptor
      antagonist carvedilol is a P-gp substrate with a log P=2.0, and can be labeled
      with [(11)C]. The aim of this study was to determine whether the P-gp substrate
      [(11)C]carvedilol can be used as a PET tracer for visualisation and
      quantification of the P-gp function in the BBB. Cellular [(11)C]carvedilol
      accumulation in GLC(4), GLC(4)/P-gp, and GLC(4)/Adr cells increased three-fold in
      the GLC(4)/P-gp cells after pretreatment with cyclosporin A (CsA) whereas no
      effect of MK571 could be determined in the GLC(4)/Adr cells. Ex vivo
      [(11)C]carvedilol biodistribution studies showed that [(11)C]carvedilol uptake in
      the brain was increased by CsA. [(11)C]carvedilol uptake in other organs was not
      affected by CsA. Autoradiography studies of rat brains showed that
      [(11)C]carvedilol was homogeneously distributed over the brain and that
      pretreatment with CsA increased [(11)C]carvedilol uptake. In vivo PET experiments
      were performed with and without P-gp modulation by CsA. P-gp mediated transport
      was quantified by Logan analysis of the PET data, calculating the distribution
      volume (DV) of [(11)C]carvedilol in the brain. Logan analysis resulted in
      excellent fits, revealing that [(11)C]carvedilol is not trapped in the brain.
      Brain DV of [(11)C]carvedilol showed a dose-dependent increase of maximal three
      fold after CsA pretreatment. Above 15 mg kg(-1), no change in DV was found.
      Compared to [(11)C]verapamil less CsA was needed to reach maximal DV, suggesting
      that [(11)C]carvedilol kinetics is a more sensitive tool to in vivo measure P-gp
      function.

PMID- 15951833
TI  - 4-Amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole (DAT1): a cytotoxic agent
      towards cancer cells and a probe for tubulin-microtubule system.
AB  - Microtubule binding drugs are of special interest as they have important roles in
      the modulation of cellular functions and many of them act as anticancer agents. 4
      Amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole (DAT1) was identified as one of
      the active compounds from a series of diaminoketothiazoles in a cell-based
      screening assay to discover cytotoxic compounds. DAT1 shows cytotoxicity with
      GI(50) values ranging from 0.05 to 1 microM in different malignant cell lines
      with an average value of 0.35 microM. It blocks mitosis in the prometaphase and
      metaphase stages. In HeLa cells, DAT1 blocks the spindle function by disturbing
      spindle microtubule and chromosome organization. The drug also inhibits assembly
      of brain microtubules and binds tubulin specifically at a single site with
      induction of fluorescence. The dissociation constant of DAT1 binding to tubulin
      was determined as 2.9+/-1 microM at 24 degrees C. The binding site of DAT1 on
      tubulin overlaps with that of the conventional colchicine-binding site. DAT1 can
      thus be considered as a lead compound of a new class of small molecules and this
      study can be used as a step to develop potent antimitotic agents for the control
      of cytoskeletal functions and cell proliferation. It would also be an interesting
      probe for the structure-function studies of tubulin-microtubule system.

PMID- 15951834
TI  - Therapeutic targeting of CCR1 attenuates established chronic fungal asthma in
      mice.
AB  - CC chemokine receptor 1 (CCR1) represents a promising target in chronic airway
      inflammation and remodeling due to fungus-associated allergic asthma. The present
      study addressed the therapeutic effect of a nonpeptide CCR1 antagonist, BX-471,
      in a model of chronic fungal asthma induced by Aspergillus fumigatus conidia. BX
      471 treatment of isolated macrophages inhibited CCL22 and TNF-alpha and promoted
      IL-10 release. BX-471 also increased toll like receptor-9 (TLR9) and decreased
      TLR2 and TLR6 expression in these cells. When administered daily by
      intraperitoneal injection, from days 15 to 30 after the initiation of chronic
      fungal asthma, BX-471 (3, 10, or 30 mg kg(-1)) dose-dependently reduced airway
      inflammation, hyper-responsiveness, and remodeling at day 30 after conidia
      challenge. The maximal therapeutic effect was observed at the 10 mg kg(-1) dose.
      In summary, the therapeutic administration of BX-471 significantly attenuated
      experimental fungal asthma via its effects on both innate and adaptive immune
      processes.

PMID- 15951835
TI  - Reliable gene expression measurements from degraded RNA by quantitative real-time
      PCR depend on short amplicons and a proper normalization.
AB  - Quantitative reverse transcriptase real-time PCR (QRT-PCR) is a robust method to
      quantitate RNA abundance. The procedure is highly sensitive and reproducible as
      long as the initial RNA is intact. However, breaks in the RNA due to chemical or
      enzymatic cleavage may reduce the number of RNA molecules that contain intact
      amplicons. As a consequence, the number of molecules available for amplification
      decreases. We determined the relation between RNA fragmentation and threshold
      values (Ct values) in subsequent QRT-PCR for four genes in an experimental model
      of intact and partially hydrolyzed RNA derived from a cell line and we describe
      the relation between RNA integrity, amplicon size and Ct values in this
      biologically homogenous system. We demonstrate that degradation-related shifts of
      Ct values can be compensated by calculating delta Ct values between test genes
      and the mean values of several control genes. These delta Ct values are less
      sensitive to fragmentation of the RNA and are unaffected by varying amounts of
      input RNA. The feasibility of the procedure was demonstrated by comparing Ct
      values from a larger panel of genes in intact and in partially degraded RNA. We
      compared Ct values from intact RNA derived from well-preserved tumor material and
      from fragmented RNA derived from formalin-fixed, paraffin-embedded (FFPE) samples
      of the same tumors. We demonstrate that the relative abundance of gene expression
      can be based on FFPE material even when the amount of RNA in the sample and the
      extent of fragmentation are not known.

PMID- 15951836
TI  - Transgenic expression of the deoxynucleotide carrier causes mitochondrial damage
      that is enhanced by NRTIs for AIDS.
AB  - Nucleoside reverse transcriptase inhibitors (NRTIs) are antiretrovirals for AIDS
      with limiting mitochondrial side effects. The mitochondrial deoxynucleotide
      carrier (DNC) transports phosphorylated nucleosides for mitochondrial DNA
      replication and can transport phosphorylated NRTIs into mitochondria. Transgenic
      mice (TG) that exclusively overexpress DNC in the heart tested DNC's role in
      mitochondrial dysfunction from NRTIs. Two TG lines were created that
      overexpressed the human DNC gene in murine myocardium. Cardiac and mitochondrial
      structure and function were examined by magnetic resonance imaging,
      echocardiography, electrocardiography, transmission electron microscopy, and
      plasma lactate. Antiretroviral combinations (HAART) that contained NRTIs
      (stavudine (2', 3'-didehydro-2', 3'-deoxythymidine or d4T)/lamivudine/indinavir;
      or zidovudine (3' azido-3'-deoxythymidine or AZT)/lamivudine/indinavir; 35 days)
      were administered to simulate AIDS therapy. In parallel, a HAART combination
      without NRTIs (nevirapine/efavirenz/indinavir; 35 days) served as an NRTI
      sparing, control regimen. Untreated DNC TGs exhibited normal cardiac function but
      abnormal mitochondrial ultrastructure. HAART that contained NRTIs caused
      cardiomyopathy in TGs with increased left ventricle mass and volume, heart rate
      variability, and worse mitochondrial ultrastructural defects. In contrast,
      treatment with an NRTI-sparing HAART regimen caused no cardiac changes. Data
      suggest the DNC is integral to mitochondrial homeostasis in vivo and may relate
      mechanistically to mitochondrial dysfunction in patients treated with HAART
      regimens that contain NRTIs.

PMID- 15951837
TI  - Renal allograft rejection is prevented by adoptive transfer of anergic T cells in
      nonhuman primates.
AB  - Anergic T cells generated ex vivo are reported to have immunosuppressive effects
      in vitro and in vivo. Here, we tested this concept in nonhuman primates.
      Alloreactive T cells were rendered anergic ex vivo by coculture with donor
      alloantigen in the presence of anti-CD80/CD86 mAbs before adoptive transfer via
      renal allograft to rhesus monkey recipients. The recipients were briefly treated
      with cyclophosphamide and cyclosporine A during the preparation of the anergic
      cells. Thirteen days after renal transplantation, the anergic T cells were
      transferred to the recipient, after which no further immunosuppressive agents
      were administered. Rejection-free survival was prolonged in all treated
      recipients, and 3 of 6 animals survived long term (410-880 days at study's end).
      In the long-surviving recipients, proliferative responses against alloantigen
      were inhibited in a donor-specific manner, and donor-type, but not third-party,
      skin allografts were also accepted, which demonstrated that antigen-specific
      tolerance had been induced. We conclude that anergic T cells generated ex vivo by
      blocking CD28/B7 costimulation can suppress renal allograft rejection after
      adoptive transfer in nonhuman primates. This strategy may be applicable to the
      design of safe clinical trials in humans.

PMID- 15951838
TI  - FGF-2 controls the differentiation of resident cardiac precursors into functional
      cardiomyocytes.
AB  - Recent evidence suggests that the heart possesses a greater regeneration capacity
      than previously thought. In the present study, we isolated undifferentiated
      precursors from the cardiac nonmyocyte cell population of neonatal hearts,
      expanded them in culture, and induced them to differentiate into functional
      cardiomyocytes. These cardiac precursors appear to express stem cell antigen-1
      and demonstrate characteristics of multipotent precursors of mesodermal origin.
      Following infusion into normal recipients, these cells home to the heart and
      participate in physiological and pathophysiological cardiac remodeling.
      Cardiogenic differentiation in vitro and in vivo depends on FGF-2. Interestingly,
      this factor does not control the number of precursors but regulates the
      differentiation process. These findings suggest that, besides its angiogenic
      actions, FGF-2 could be used in vivo to facilitate the mobilization and
      differentiation of resident cardiac precursors in the treatment of cardiac
      diseases.

PMID- 15951839
TI  - T cell hyperactivity in lupus as a consequence of hyperstimulatory antigen
      presenting cells.
AB  - Sle3 is an NZM2410-derived lupus susceptibility locus on murine chromosome 7.
      Congenic recombination has resulted in a novel mouse strain, B6.Sle3, associated
      with serum antinuclear autoantibodies (ANAs), T cell hyperactivity, and elevated
      CD4/CD8 ratios. An OVA-specific TCR transgene was used as a tool to demonstrate
      that Sle3 facilitated heightened T cell expansion in vitro, and in vivo,
      following antigen challenge. Indeed, continued T cell expansion was noted even in
      response to a tolerogenic signal. However, these phenotypes did not appear to be
      T cell intrinsic but were dictated by hyperstimulatory B6.Sle3 APCs. Importantly,
      B6.Sle3-derived DCs and macrophages appeared to be significantly more
      mature/activated, less apoptotic, and more proinflammatory and were better at
      costimulating T cells in vitro, compared with the B6 counterparts. Finally, the
      adoptive transfer of B6.Sle3-derived DCs into healthy B6 recipients elicited
      increased CD4/CD8 ratios and serum ANAs, 2 cardinal Sle3-associated phenotypes.
      We posit that their heightened expression of various costimulatory molecules,
      including CD80, CD106, I-A, and CD40, and their elevated production of various
      cytokines, including IL-12 and IL-1beta, may explain why Sle3-bearing DCs may be
      superior at breaching self tolerance. These studies provide mechanistic evidence
      indicating that intrinsic abnormalities in DCs and possibly other myeloid cells
      may dictate several of the phenotypes associated with systemic lupus, including
      ANA formation and T cell hyperactivity.

PMID- 15951840
TI  - Functional, structural, and metabolic abnormalities of the hippocampal formation
      in Williams syndrome.
AB  - Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome
      7q11.23, is characterized by dysmorphic features, mental retardation or learning
      difficulties, elastin arteriopathy, and striking neurocognitive and social
      behavioral abnormalities. Recent studies of murine knockouts of key genes in the
      microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2
      (CYLN2), demonstrated significant functional and metabolic abnormalities, but
      grossly normal structure, in the hippocampal formation (HF). Furthermore,
      deficits in spatial navigation and long-term memory, major cognitive domains
      dependent on hippocampal function, have been described in WS. We used multimodal
      neuroimaging to characterize hippocampal structure, function, and metabolic
      integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy
      controls. PET and functional MRI studies showed profound reduction in resting
      blood flow and absent differential response to visual stimuli in the anterior HF
      in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of
      synaptic activity, were reduced. Hippocampal size was preserved, but subtle
      alterations in shape were present. These data demonstrate abnormalities in HF in
      WS in agreement with murine models, implicate LIMK1 and CYLN2 in human
      hippocampal function, and suggest that hippocampal dysfunction may contribute to
      neurocognitive abnormalities in WS.

PMID- 15951841
TI  - Fertility in luteinizing hormone receptor-knockout mice after wild-type ovary
      transplantation demonstrates redundancy of extragonadal luteinizing hormone
      action.
AB  - The luteinizing hormone receptor (LHR), mainly expressed in gonads, is essential
      for normal reproduction. However, numerous recent studies have also demonstrated
      LHR expression in multiple extragonadal reproductive and nonreproductive tissues.
      Although some effects of luteinizing hormone (LH) or its agonist, human chorionic
      gonadotropin, have been shown in extragonadal sites, their physiological
      significance remains open. In the present study, we have addressed the function
      of the extragonadal LHR using LHR-KO mice (LuRKO mice), in which the ovaries of
      prepubertal mice were orthotopically replaced with pieces of WT ovary using
      similarly transplanted WT mice as controls. Most ovarian transplants attained
      normal endocrine function in both groups of mice, as demonstrated by normal age
      at vaginal opening, estrous cycles, and sexual behavior. Both the LuRKO and WT
      mice repeatedly became pregnant (9/16 vs. 16/20 after first mating; difference
      not significant) and delivered similarly sized litters, which grew normally after
      birth, indicating normal lactation. In conclusion, fertility is restored in LuRKO
      mice by transplantation of WT ovarian tissue. This is achieved in the absence of
      extragonadal LHR expression, which indicates physiological redundancy for such
      receptor sites.

PMID- 15951842
TI  - Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate
      growth plate length independently of PTHrP.
AB  - In the developing growth plate, periarticular chondrocytes proliferate,
      differentiate into columnar chondrocytes, and then further differentiate into
      postmitotic hypertrophic chondrocytes. Parathyroid hormone-related (PTH-related)
      protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature
      hypertrophic differentiation, thereby maintaining the length of columns. Ihh
      regulates cartilage development through PTHrP-independent pathways as well. Here
      we show that Ihh stimulates differentiation of periarticular to columnar
      chondrocytes (periarticular chondrocyte differentiation) and thereby regulates
      the length of columns independently of PTHrP. Mosaic ablation of the PTH/PTHrP
      receptor in the growth plate caused upregulation of Ihh action, PTHrP
      upregulation, acceleration of periarticular chondrocyte differentiation, and
      elongation of the columnar region. Decreasing Ihh action in these mice reduced
      elongation of columns, whereas decreasing PTHrP showed only a modest effect on
      column length. Overexpression of Ihh caused PTHrP upregulation, elongation of
      columns, and acceleration of periarticular chondrocyte differentiation. PTHrP
      heterozygosity in this model had a minimal effect on the elongation of columns.
      Moreover, the elongation of columns and stimulation of periarticular chondrocyte
      differentiation in these models were still observed when PTHrP signaling was
      maintained so that it remained constant. These results demonstrate that Ihh acts
      on periarticular chondrocytes to stimulate their differentiation, thereby
      regulating the columnar cell mass independently of PTHrP.

PMID- 15951843
TI  - NO mediates mural cell recruitment and vessel morphogenesis in murine melanomas
      and tissue-engineered blood vessels.
AB  - NO has been shown to mediate angiogenesis; however, its role in vessel
      morphogenesis and maturation is not known. Using intravital microscopy,
      histological analysis, alpha-smooth muscle actin and chondroitin sulfate
      proteoglycan 4 staining, microsensor NO measurements, and an NO synthase (NOS)
      inhibitor, we found that NO mediates mural cell coverage as well as vessel
      branching and longitudinal extension but not the circumferential growth of blood
      vessels in B16 murine melanomas. NO-sensitive fluorescent probe 4,5
      diaminofluorescein imaging, NOS immunostaining, and the use of NOS-deficient mice
      revealed that eNOS in vascular endothelial cells is the predominant source of NO
      and induces these effects. To further dissect the role of NO in mural cell
      recruitment and vascular morphogenesis, we performed a series of independent
      analyses. Transwell and under-agarose migration assays demonstrated that
      endothelial cell-derived NO induces directional migration of mural cell
      precursors toward endothelial cells. An in vivo tissue-engineered blood vessel
      model revealed that NO mediates endothelial-mural cell interaction prior to
      vessel perfusion and also induces recruitment of mural cells to angiogenic
      vessels, vessel branching, and longitudinal extension and subsequent
      stabilization of the vessels. These data indicate that endothelial cell-derived
      NO induces mural cell recruitment as well as subsequent morphogenesis and
      stabilization of angiogenic vessels.

PMID- 15951844
TI  - RNA interference is ineffective as a routine method for gene silencing in chick
      embryos as monitored by fgf8 silencing.
AB  - The in vivo accessibility of the chick embryo makes it a favoured model system
      for experimental developmental biology. Although the range of available
      techniques now extends to miss-expression of genes through in ovo
      electroporation, it remains difficult to knock out individual gene expression.
      Recently, the possibility of silencing gene expression by RNAi in chick embryos
      has been reported. However, published studies show only discrete quantitative
      differences in the expression of the endogenous targeted genes and unclear
      morphological alterations. To elucidate whether the tools currently available are
      adequate to silence gene expression sufficiently to produce a clear and specific
      null-like mutant phenotype, we have performed several experiments with different
      molecules that trigger RNAi: dsRNA, siRNA, and shRNA produced from a plasmid
      coexpressing green fluorescent protein as an internal marker. Focussing on fgf8
      expression in the developing isthmus, we show that no morphological defects are
      observed, and that fgf8 expression is neither silenced in embryos microinjected
      with dsRNA nor in embryos microinjected and electroporated with a pool of siRNAs.
      Moreover, fgf8 expression was not significantly silenced in most isthmic cells
      transformed with a plasmid producing engineered shRNAs to fgf8. We also show that
      siRNA molecules do not spread significantly from cell to cell as reported for
      invertebrates, suggesting the existence of molecular differences between
      different model systems that may explain the different responses to RNAi.
      Although our results are basically in agreement with previously reported studies,
      we suggest, in contrast to them, that with currently available tools and
      techniques the number of cells in which fgf8 gene expression is decreased, if
      any, is not sufficient to generate a detectable mutant phenotype, thus making
      RNAi useless as a routine method for functional gene analysis in chick embryos.

PMID- 15951845
TI  - Partial mitochondrial genome sequences of Ostrinia nubilalis and Ostrinia
      furnicalis.
AB  - Contiguous 14,535 and 14,536 nt near complete mitochondrial genome sequences
      respectively were obtained for Ostrinia nubilalis and Ostrinia furnicalis.
      Mitochondrial gene order was identical to that observed from Bombyx. Sequences
      comparatively showed 186 substitutions (1.3% sequence divergence), 170 CDS
      substitutions (131 at 3(rd) codon positions), and an excess of transition
      mutation likely resulting by purifying selection (d(N)/d(S) = omega congruent
      with 0.15). Overall substitution rates were significantly higher at 4-fold (5.2%)
      compared to 2-fold degenerate codons (2.6%). These are the 3(rd) and 4(th)
      lepidopteran mitochondrial genome reference sequences in GenBank and useful for
      comparative mitochondrial studies.

PMID- 15951846
TI  - No more than 14: the end of the amphioxus Hox cluster.
AB  - The Hox gene cluster has been a key paradigm for a generation of developmental
      and evolutionary biologists. Since its discovery in the mid-1980's, the
      identification, genomic organization, expression, colinearity, and regulation of
      Hox genes have been immediate targets for study in any new model organism, and
      metazoan genome projects always refer to the structure of the particular Hox
      cluster(s). Since the early 1990's, it has been dogma that vertebrate Hox
      clusters are composed of thirteen paralogous groups. Nonetheless, we showed that
      in the otherwise prototypical cephalochordate amphioxus (Branchiostoma floridae),
      the Hox cluster contains a fourteenth Hox gene, and very recently, a 14(th) Hox
      paralogous group has been found in the coelacanth and the horn shark, suggesting
      that the amphioxus cluster was anticipating the finding of Hox 14 in some
      vertebrate lineages. In view of the pivotal place that amphioxus occupies in
      vertebrate evolution, we thought it of considerable interest to establish the
      limits of its Hox gene cluster, namely resolution of whether more Hox genes are
      present in the amphioxus cluster (e.g., Hox 15). Using two strategies, here we
      report the completion and characterization of the Hox gene content of the single
      amphioxus Hox cluster, which encompasses 650 kb from Hox1 to Evx. Our data have
      important implications for the primordial Hox gene cluster of chordates: the
      prototypical nature of the single amphioxus Hox cluster makes it unlikely that
      additional paralogous groups will be found in any chordate lineage. We suggest
      that 14 is the end.

PMID- 15951847
TI  - Diversity of endophytic fungal community of cacao (Theobroma cacao L.) and
      biological control of Crinipellis perniciosa, causal agent of Witches' Broom
      Disease.
AB  - The basidiomycete fungus Crinipellis perniciosa (Stahel) Singer is the causal
      agent of Witches' Broom Disease of Cacao (Theobromacacao L.) which is the main
      factor limiting cacao production in the Americas. Pod losses of up to 90% are
      experienced in affected areas as evidenced by the 50% drop in production in Bahia
      province, Brazil following the arrival of the C. perniciosa in the area in 1989.
      The disease has proven particularly difficult to control and many farmers in
      affected areas have given up cacao cultivation. In order to evaluate the
      potential of endophytes as a biological control agent of this phytopathogen, the
      endophytic fungal community of resistant and susceptible cacao plants as well as
      affected branches was studied between 2001 and 2002. The fungal community was
      identified by morphological traits and rDNA sequencing as belonging to the genera
      Acremonium, Blastomyces, Botryosphaeria, Cladosporium, Colletotrichum, Cordyceps,
      Diaporthe, Fusarium, Geotrichum, Gibberella, Gliocladium, Lasiodiplodia,
      Monilochoetes, Nectria, Pestalotiopsis, Phomopsis, Pleurotus, Pseudofusarium,
      Rhizopycnis, Syncephalastrum, Trichoderma, Verticillium and Xylaria. These fungi
      were evaluated both in vitro and in vivo by their ability to inhibit C.
      perniciosa. Among these, some were identified as potential antagonists, but only
      one fungus (Gliocladium catenulatum) reduced the incidence of Witches' Broom
      Disease in cacao seedlings to 70%.

PMID- 15951848
TI  - Influence of dissolved oxygen concentration on intracellular pH for regulation of
      Aspergillus niger growth rate during citric acid fermentation in a stirred tank
      bioreactor.
AB  - In this paper we report the regulation of Aspergillus niger growth rate during
      citric acid fermentation in a stirred tank bioreactor. For this, the influence of
      dissolved oxygen concentration in a medium on intracellular pH values and
      consequently on overall microbial metabolism was emphasized. Intracellular pH of
      mycelium grown under different concentrations of dissolved oxygen in the medium
      was determined. Sensitivity of proteins toward proton concentration is well
      recognized, therefore pH influences on the activities of key regulatory enzymes
      of Aspergillus niger were determined at pH values similar to those detected in
      the cells grown under lower dissolved oxygen concentrations. The results have
      shown significantly reduced specific activities of hexokinase, 6
      phosphofructokinase and glucose-6-phosphate dehydrogenase in more acidic
      environment, while pyruvate kinase was found to be relatively insensitive towards
      higher proton concentration. As expected, due to the reduced specific activities
      of regulatory enzymes under more acidic conditions, overall metabolism should be
      hindered in the medium with lower dissolved oxygen concentration which was
      confirmed by detecting the reduced specific growth rates. From the studies, we
      conclude that dissolved oxygen concentration affects the intracellular pH and
      thus growth rate of Aspergillus niger during the fermentation process.

PMID- 15951849
TI  - PIKE GTPase signaling and function.
AB  - PIKE (PI 3-Kinase Enhancer) is a recently identified brain specific nuclear
      GTPase, which binds PI 3-kinase and stimulates its lipid kinase activity. Nerve
      growth factor treatment leads to PIKE activation by triggering the nuclear
      translocation of phospholipase C-gamma1 (PLC-gamma1), which acts as a physiologic
      guanine nucleotide exchange factor (GEF) for PIKE through its SH3 domain. To
      date, three forms of PIKE have been characterized: PIKE-S, PIKE-L and PIKE-A.
      PIKE-S is initially identified shorter isoform. PIKE-L, a longer isoform of PIKE
      gene, differs from PIKE-S by C-terminal extension containing Arf-GAP (ADP
      ribosylation factor-GTPase Activating Protein) and two ankyrin repeats domains.
      In contrast to the exclusive nuclear localization of PIKE-S, PIKE-L occurs in
      both the nucleus and the cytoplasm. PIKE-L physiologically associates with Homer
      1, an mGluR I binding adaptor protein. The Homer/PIKE-L complex couples PI 3
      kinase to mGluR I and regulates a major action of group I mGluRs, prevention of
      neuronal apoptosis. More recently, a third PIKE isoform, PIKE-A was identified in
      human glioblastoma multiforme brain cancers. Unlike the brain specific PIKE-L and
      -S isoforms, PIKE-A distributes in various tissues. PIKE-A contains the same
      domains present in PIKE-L but lacks N-terminal proline-rich domain (PRD), which
      binds PI 3-kinase and PLC-gamma1. Instead, PIKE-A specifically binds to active
      Akt and upregulates its activity in a GTP-dependent manner, mediating human
      cancer cell invasion and preventing apoptosis. Thus, PIKE extends its roles from
      the nucleus to the cytoplasm, mediating cellular processes from cell invasion to
      programmed cell death.

PMID- 15951850
TI  - The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits.
AB  - The heterotrimeric G-protein alpha subunit has long been considered a bimodal,
      GTP-hydrolyzing switch controlling the duration of signal transduction by seven
      transmembrane domain (7TM) cell-surface receptors. In 1996, we and others
      identified a superfamily of "regulator of G-protein signaling" (RGS) proteins
      that accelerate the rate of GTP hydrolysis by Galpha subunits (dubbed GTPase
      accelerating protein or "GAP" activity). This discovery resolved the paradox
      between the rapid physiological timing seen for 7TM receptor signal transduction
      in vivo and the slow rates of GTP hydrolysis exhibited by purified Galpha
      subunits in vitro. Here, we review more recent discoveries that have highlighted
      newly-appreciated roles for RGS proteins beyond mere negative regulators of 7TM
      signaling. These new roles include the RGS-box-containing, RhoA-specific guanine
      nucleotide exchange factors (RGS-RhoGEFs) that serve as Galpha effectors to
      couple 7TM and semaphorin receptor signaling to RhoA activation, the potential
      for RGS12 to serve as a nexus for signaling from tyrosine kinases and G-proteins
      of both the Galpha and Ras-superfamilies, the potential for R7-subfamily RGS
      proteins to couple Galpha subunits to 7TM receptors in the absence of
      conventional Gbetagamma dimers, and the potential for the conjoint 7TM/RGS-box
      Arabidopsis protein AtRGS1 to serve as a ligand-operated GAP for the plant Galpha
      AtGPA1. Moreover, we review the discovery of novel biochemical activities that
      also impinge on the guanine nucleotide binding and hydrolysis cycle of Galpha
      subunits: namely, the guanine nucleotide dissociation inhibitor (GDI) activity of
      the GoLoco motif-containing proteins and the 7TM receptor-independent guanine
      nucleotide exchange factor (GEF) activity of Ric8/synembryn. Discovery of these
      novel GAP, GDI, and GEF activities have helped to illuminate a new role for
      Galpha subunit GDP/GTP cycling required for microtubule force generation and
      mitotic spindle function in chromosomal segregation.

PMID- 15951851
TI  - The multiple personalities of the regulatory subunit of protein kinase CK2: CK2
      dependent and CK2 independent roles reveal a secret identity for CK2beta.
AB  - Protein kinase CK2 (formerly casein kinase II), an enzyme that participates in a
      wide variety of cellular processes, has traditionally been classified as a stable
      tetrameric complex consisting of two catalytic CK2alpha or CK2alpha' subunits and
      two regulatory CK2beta subunits. While consideration of CK2 as a tetrameric
      complex remains relevant, significant evidence has emerged to challenge the view
      that its individual subunits exist exclusively within these complexes. This
      review will summarize biochemical and genetic evidence indicating that the
      regulatory CK2beta subunit exists and performs functions independently of CK2
      tetramers. For example, unbalanced expression of catalytic and regulatory CK2
      subunits has been observed in a variety of tissues and tumors. Furthermore,
      localization studies including live cell imaging have demonstrated that while the
      catalytic and regulatory subunits of CK2 exhibit extensive co-localization,
      independent mobility of the individual CK2 subunits can also be observed within
      cells. Identification of proteins that interact with CK2beta in the absence of
      catalytic CK2 subunits reinforces the notion that CK2beta has functions distinct
      from CK2 and begins to offer insights into these CK2-independent functions. In
      this respect, the discovery that CK2beta can interact with and modulate the
      activity of a number of other serine/threonine protein kinases including A-Raf, c
      Mos and Chk1 is particularly striking. This review will discuss the interactions
      between CK2beta and these protein kinases with special emphasis on the properties
      of CK2beta that mediate these interactions and on the implications of these
      interactions in yielding new prospects for elucidation of the cellular functions
      of CK2beta.

PMID- 15951852
TI  - Dissecting Nck/Dock signaling pathways in Drosophila visual system.
AB  - The establishment of neuronal connections during embryonic development requires
      the precise guidance and targeting of the neuronal growth cone, an expanded
      cellular structure at the leading tip of a growing axon. The growth cone contains
      sophisticated signaling systems that allow the rapid communication between
      guidance receptors and the actin cytoskeleton in generating directed motility.
      Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter
      protein in photoreceptor (R cell) axon guidance and target recognition in the
      Drosophila visual system, suggesting strongly that Nck/Dock is one of the long
      sought missing links between cell surface receptors and the actin cytoskeleton.
      In this review, I discuss the recent progress on dissecting the Nck/Dock
      signaling pathways in R-cell growth cones. These studies have identified
      additional key components of the Nck/Dock signaling pathways for linking the
      receptor signaling to the remodeling of the actin cytoskeleton in controlling
      growth-cone motility.

PMID- 15951854
TI  - Urolithiasis in adults. Clinical and biochemical aspects.
AB  - Urolithiasis is a multifactorial recurrent disease of world-wide distribution in
      rural, urban, industrial and non-industrial regions. Changes in urinary pH is a
      risk factor especially with hyperuricosuria, hypercalciuria or hyperoxaluria.
      With recurrence, hypercalcuria and higher urinary oxalate levels are more
      frequent. Hypercalciuria and hyperuricosuria showed correlation with family
      history of stones. The ionic relations between various stone forming salts in
      urine of patients are opposite to that in controls and are well represented in
      stone composition. Obesity is a risk factor in both genders. Over eating a diet
      rich in all nutrients was associated with hyperuricosuria while a diet high only
      in fat was associated with other urinary disturbances. High protein and fat
      intake are risk factors. High or low calcium diet was associated with
      urolithiasis and supplemental calcium is not a risk factor. Potassium and
      magnesium citrate are potent in inhibiting the growth of stone fragments after
      extracorporeal shock wave lithotripsy. Whether in patients or normal subjects,
      drinking hard water should be avoided; tap water or low calcium content water is
      preferable. Seasonal variations in temperature affected urinary volume, pH and
      relative saturation of uric acid. To prevent recurrence, patients should maintain
      high fluid intake achieving a urine volume of 2 liters per day.

PMID- 15951853
TI  - Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal
      morphogenesis, regeneration and transformation.
AB  - The epidermis is the outermost layer in the skin, and it is the first line of
      defence against the environment. The epidermis also provides a barrier against
      loss of fluids and electrolytes, which is crucial for life. Essential in the
      maintenance of this tissue is its ability to continually self-renew and
      regenerate after injury. These two characteristics are critically dependent on
      the ability of the principal epidermal cell type, the keratinocyte, to
      proliferate and to respond to differentiation cues. Indeed, the epidermis is a
      multilayered tissue composed of keratinocyte stem cells and their differentiated
      progeny. Central for the control of cell proliferation is the E2F transcription
      factor regulatory network. This signaling network also includes cyclins, cdk, cdk
      inhibitors and the retinoblastoma (pRb) family of proteins. The biological
      importance of the E2F/pRb pathway is emphasized by the fact that a majority of
      human tumours exhibit alterations that disrupt the ability of pRb proteins to
      inhibit E2F, leading to permanent activation of the latter. Further, E2F is
      essential for normal epidermal regeneration after injury. Other member of the E2F
      signaling pathway are also involved in epidermal development and pathophysiology.
      Thus, whereas the pRb family of proteins is essential for epidermal
      morphogenesis, abnormal regulation of cyclins and E2F proteins results in
      tumorgenesis in this tissue. In this review, we discuss the role of each member
      of this important growth regulatory network in epidermal formation, homeostasis
      and carcinogenesis.

PMID- 15951855
TI  - Influence of parathyroid hormone-related peptide gene in colon cancer cell line
      growth.
AB  - OBJECTIVE: Parathyroid hormone-related peptide (PTHrP) has been found to be
      express in different human tumors including colon. We used a human colon cell
      line (Lovo) as a model to study the mechanism for the proliferation effects of
      PTHrP. METHODS: This study was conducted in the Department of Pharmacology at
      University of Texas Medical Branch, Galveston, Texas, United States of America
      and Department of Biochemistry at College of Science King Saud University,
      Riyadh, Kingdom of Saudi Arabia from June 2001 until September 2003. The PTHrP
      constructs expressing in sense or antisense orientation were constructed by
      cloning human PTHrP cDNA and transfected into Lovo cells. Single clone of stably
      transfected cells was isolated and grown for 2, 4 and 7 days. RESULTS: The
      proliferation rate of Lovo clones with sense overexpressing PTHrP was less rapid
      than that of antisense or empty vector transfected cells; however, at day 7 the
      cell number of the antisense PTHrP overexpressing clones was more than 2-folds
      compared with the empty vector transfected clones. CONCLUSION: The sense PTHrP
      gene blocks translation decrease the cell growth, which might be significant
      implications for the role of PTHrP in colon cancer.

PMID- 15951856
TI  - Clinical implication of vascular and dimensional aspects of the cricothyroid
      space in the Turkish population.
AB  - OBJECTIVE: Cricothyroid space (CS) is one of the thinnest part in the framework
      of the larynx. The close relations of CS to the intralaryngeal subglottic area
      increase its anatomical importance. The aim of this study was to establish
      topographic distribution and the number of perforating vessels lying towards the
      intralaryngeal subglottic region and finding the calibrations of these vessels,
      thus revealing an index for the Turkish population. METHODS: In this study, 5
      women and 45 men autopsy materials that had no pathology or previous surgery in
      the area were examined during the period February to November 2003. All specimens
      in this study were selected randomly from the criminal lab of the Republic of
      Turkey Ministry of Justice, Istanbul, Turkey. Microdissections were made by SMZ
      10 Stereomicroscope. Superficial vascular structures of the membrane
      cricothyroidea at CS and their crossing places (foramens) to the intralaryngeal
      area, their numbers and localizations in relation to the midline (right/left and
      cranial/caudal) and their diameters were established. RESULTS: In the larynx
      dissections, which were made in 50 cases, a total of 180 vessels were seen.
      Seventy-eight vessels were situated on the middle line (cranial and caudal).
      Fifty-three vessels were at right side (cranial and caudal) and 49 vessels were
      at left side (cranial and caudal). In 20 specimens 2-4 vessels arrangement were
      passing through the foramen to the intralaryngeal subglottic area. Among these
      foramens, 20 of them consisted of 2 vessels (16 cranial, 4 caudal), 4 of 3
      vessels (3 cranial, 1 caudal) and only one foramen was consist of 4 vessels
      (cranial). CONCLUSION: The cricothyroid area is an anatomical compartment
      enclosed by a connective tissue membrane and connected to the adjacent laryngeal
      region by vessels. This region is important with regard to surgical procedures,
      spread of laryngeal cancer and traumatic lesions of the larynx. Therefore, the
      clinical and surgical importance of vascular anatomy and the dimension of the
      cricothyroid space should be given emphasis in our population.

PMID- 15951857
TI  - Synergistic effect of the combination triclosan with 2-phenylphenol against
      Pseudomonas aeruginosa and fungi.
AB  - OBJECTIVE: Triclosan is active against Gram-positive and Gram-negative bacteria
      but lesser against Pseudomonas aeruginosa (P.aeruginosa). 2-phenylphenol is
      considered as an effective agent against fungi but its antifungal action is more
      important than its antibacterial activity. The aim of this study is to evaluate
      the bactericidal and fungicidal activities of triclosan and 2-phenylphenol alone,
      and in combination against standard strains of bacteria and fungi. METHODS: The
      study was carried out in the Research Laboratory of Pharmaceutical Microbiology,
      Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan,
      during the year 2004. The standard French method of in-vitro dilution
      quantitative suspension test, according to the Association Francoise de
      Normalization (AFNOR) guideline, has been used to determine the antibacterial and
      antifungal activity of each agent alone as well as the combination of the agents.
      RESULTS: The antibacterial activity of the combination triclosan-2-phenylphenol
      was significantly enhanced over that of each agent used alone against
      P.aeruginosa. Synergistic effect was observed against all tested strains of
      fungi. CONCLUSION: This synergistic effect that was exhibited by triclosan-2
      phenylphenol combination can be considered to enhance the antibacterial activity
      against P.aeruginosa and the antifungal activity of the 2 agents, to reduce the
      in-use concentration of each agent used alone, that may minimize any possible
      side effect of the 2 agents, and to avoid the occurrence of bacterial resistance
      to one of the 2 agents.

PMID- 15951858
TI  - Expression of nm23 antimetastatic gene product in parathyroid hyperplasia,
      adenoma and carcinoma. An immunohistological assessment.
AB  - OBJECTIVE: The nm23 gene was initially cloned as a metastasis suppressor gene,
      but the clinical relevance of nm23 as a metastasis suppressor or prognostic
      indicator for human cancers remain controversial. To evaluate the role of nm23
      protein as a prognostic factor and its role in parathyroid neoplasia, we studied
      nm23 protein expression by immunohistochemical staining in parathyroid lesions.
      METHODS: Immunohistochemistry using the avidin-biotin peroxidase complex
      technique with a polyclonal antibody against the nm23 protein was applied to
      formalin-fixed, paraffin-embedded tissue specimens obtained from 48 patients. The
      specimens were collected from 38 patients at the University Health Network,
      Toronto, Canada and from 10 Saudi patients at the King Abdul-Aziz University
      Hospital, Jeddah, Kingdom of Saudi Arabia. They included parathyroid carcinomas
      (5 cases), adenomas (22 cases), hyperplasia (21 cases), and normal parathyroid
      tissue (10 cases). The immunohistochemistry was completed in 2003 at King Abdul
      Aziz University Hospital, Jeddah, KSA and University Health Network, Toronto,
      Canada. RESULTS: Expression of nm23 protein was noted in adenomas and carcinomas
      as well as in hyperplastic parathyroid glands and there was no significant
      statistical difference between these groups. Normal parathyroid glands did not
      show any intense immunoreactivity. CONCLUSION: The results suggest that
      expression of nm23 in parathyroid lesions is correlated with tumor proliferation
      rather than suppression of invasion and metastasis. While our data suggest that
      nm23 may help in the distinction of normal from proliferative parathyroids, these
      results do not point to nm23 as a reliable prognostic marker in parathyroid
      lesions.

PMID- 15951859
TI  - Genetic screening of familial Mediterranean fever mutations in the Palestinian
      population.
AB  - OBJECTIVE: To investigate the spectrum of mutations and genotypes in the pyrin
      gene in familial Mediterranean fever (FMF) patients. METHODS: Blood samples of
      511 suspected FMF patients, received from the Molecular Genetics Laboratory,
      Makassed Islamic Charitable Hospital, Mount Olives, Jerusalem during the period
      from June 1999 to August 2004, were investigated by genotyping 24 different MEFV
      mutations. RESULTS: Our work revealed the presence of 14 different mutations from
      the identified 24 mutations in the gene which are assembled in 6 homozygous, 9
      heterozygous and 16 compound heterozygous genotypes. The homozygous genotypes
      represent the predominant format among our patients representing approximately
      38% of the revealed genotypes. Interestingly, in 94 (31.4%) of the tested
      subjects, only one mutation in the pyrin gene could be identified while the other
      mutant allele remains unidentified. Moreover, the genotype of 3 (1%) patients
      revealed the presence of triplet mutations in the pyrin gene. CONCLUSION: The
      results of our study clearly suggest that the origin of FMF among the Palestinian
      population is mostly homozygous. The identification of a significant number of
      patients with one known mutation indicates potentially the presence of new
      mutations in the gene which will be investigated in the future.

PMID- 15951860
TI  - Ocular profile among hearing impaired children.
AB  - OBJECTIVE: To report ocular abnormalities among identified hearing impaired
      children and their prevalence in relation to normal hearing children. METHODS: A
      sample of 302 identified children with bilateral sensorineural hearing loss at
      King Abdul-Aziz University Hospital and Rehabilitation Medical Center of the
      Ministry of Health, Riyadh, Kingdom of Saudi Arabia, after full audiological
      assessment, aged below 15 years, were screened ophthalmologically during the
      period from December 1997 to December 2002. Visual testing and cycloplegic
      refraction using 1% Cyclogyl was performed followed by retinal examination using
      direct and indirect ophthalmoscopy. Electroretinography was recorded for those
      with retinal pigmentary changes. One hundred control normal hearing children were
      examined, and chi square test applied. RESULTS: A total of 302 hearing impaired
      children were examined, 199 (66%) were boys and 103 (34%) were girls, age ranged
      between 2-15 years. Hearing loss was bilateral severe to profound. One hundred
      and eighty-four (61%) have one or more ocular abnormalities, while 147 (48.7%)
      had one or more significant error of refraction. In the control cases, 23% had
      error of refraction with a chi square test of 20.2 (p<0.001), which is
      significant. CONCLUSION: Ocular anomalies are more commonly found among deaf
      children than those with normal hearing. Early ophthalmological assessment of
      hearing impairment is advisable to detect any ocular anomalies, followed by
      correction to help in the academic performance of these children.

PMID- 15951861
TI  - The effects of birth interval on intellectual development of Saudi school
      children in Eastern Saudi Arabia.
AB  - OBJECTIVE: The primary aim of this study was to investigate the effect of birth
      intervals on some aspects of intellectual ability of Saudi primary school boys.
      METHODS: This is a cross-sectional study of Saudi school children comparing their
      intellectual ability (general intelligence) in relation to the length of the
      birth interval before and after the birth of the index child. The study area
      comprised 3 townships in the eastern province; Khobar, Thogba and Dhahran. The
      study was conducted in 2000/2001 and the study population comprised Saudi primary
      school boys aged 9-10 years from a middle class background. A 2 stage random
      sampling technique was adopted. Data were collected using student data sheet, a
      family questionnaire and the Standard Progressive Raven Matrices Test of
      intellectual ability, standardized for use in Saudi Arabia. Data were analyzed
      using SPSS software. RESULTS: More than 90% of children born after a birth
      interval greater than 35 months were classified as average and above according to
      the Raven Matrices Test, compared to 79% of children born after a birth interval
      of less than 19 months (p<0.03). Analysis of variance showed that test scores
      increased consistently as the succeeding birth interval increased. Multivariate
      analysis showed the most import predicting variables in the Raven Matrices Test
      to be family income and height. CONCLUSION: Longer birth intervals were shown to
      be associated with higher general intelligence levels in the 9-10 year olds.
      These results confirm those obtained in a previous study in Singapore conducted
      more than 2 decades ago. Our results have also shown that the succeeding birth
      interval is more significant than the preceding interval in relation to
      perceptive ability of children. The findings enable us to advise parents that by
      observing a birth interval between 2-3 years would make their children grow and
      do better at school.

PMID- 15951862
TI  - Chloral hydrate. An effective agent for sedation in children with age and weight
      dependent response.
AB  - OBJECTIVE: Diagnostic and therapeutic procedures in children are made easier
      using sedation. However, there is no consensus about which drug should be used to
      achieve this. Furthermore, none of the drugs used for sedation are risk free. The
      aim of this work is to study sedation indications, effectiveness, and safety at
      our center. METHODS: A prospective observational study conducted at the Pediatric
      Day Care Unit, King Fahad National Guard Hospital, Riyadh, Saudi Arabia. The
      study covered 17.5 weeks in 2 periods: May 9th 1999 to June 13th 1999 and October
      31st 2001 to February 11th 2002. Children <12 years were included. Collected data
      included demographics, indication, drug dosing and outcome. Data were reported as
      mean +/- SD. RESULTS: We included 148 patients, age 38 +/- 30 months. Adequate
      sedation was achieved in 79% after initial chloral hydrate (CH) dose of 56.9 +/-
      9.3 mg/kg, in 95% after adding 18.5 +/- 6.4 mg/kg CH and in 96% after adding
      second drug. Compared to nonrespondents, first CH dose respondents were younger
      and lower in weight. The CH side effects were few and mild. CONCLUSION: Chloral
      hydrate is a safe and effective agent for sedation in children with an age and
      weight dependent response.

PMID- 15951863
TI  - Clinical features of extrapulmonary tuberculosis in children.
AB  - OBJECTIVE: To review the clinical features of the extrapulmonary tuberculosis
      (TB) in children. METHODS: Sixty-four children with extrapulmonary TB followed in
      Ankara Social Security Children's Hospital between June 1995 and May 2003 were
      reviewed. RESULTS: The mean age was 7.5 +/- 4.1 years. The most commonly involved
      sites were the central nervous system [(CNS) 16 cases] and pleura (14 cases).
      Aside from this, 10 children had a diagnosis of miliary TB. Abdominal TB (median
      age of 12 years) and pleural effusion (median age of 10.9 years) were mostly seen
      in older children while miliary TB was encountered more frequently in younger
      children (median age 2.5 years). A positive family history of active TB was
      detected in 39% of the cases. There was consanguinity between parents in 23
      (35.9%) of the cases. Twenty-five (39%) cases had no Bacillus Calmette-Guerin
      vaccination scar. One case with CNS TB expired. Sequelae observed during the
      follow up were; motor-mental retardation in 3 cases, hemiparesis in 2 cases,
      strabismus in one case with CNS TB and vertebral deformation in 2 cases with
      Pott's disease. CONCLUSION: Severe forms such as CNS and miliary TB constituted
      an important percentage of childhood extrapulmonary TB cases.

PMID- 15951864
TI  - Comparison of clinico-radiological features of patients with positive cultures of
      nontuberculous mycobacteria and patients with tuberculosis.
AB  - OBJECTIVE: To identify the clinico-radiological features of patients with
      positive cultures for nontuberculous mycobacteria (NTM) and compare those to a
      sample of patients with tuberculosis (MTB). METHODS: A laboratory database was
      used to retrieve all specimens submitted to King Khalid University Hospital,
      Riyadh, mycobacteriology laboratory for mycobacterial smears and cultures during
      the period from October 1999-April 2002. Using this database, the original
      records of the mycobacteriology laboratory and a review of the patient's health
      records, a standard proforma was completed that included demographic, clinical,
      radiological and laboratory information on patients included in this study. The
      patients were divided into 2 groups; the NTM group, which included all patients
      with positive cultures for NTM and the MTB group, which included a sample of
      patients with documented tuberculosis. RESULTS: During the study period, 286
      patients had positive mycobacterial cultures. Seventy patients (24.5%) grew NTM
      and 216 (75.5%) grew MTB. For patients with MTB, 54 patients were included as per
      the selection protocol of the study. There was no difference between the 2 groups
      in all measured demographic variables. The presence of weight loss and fever was
      significantly more in the MTB group. Radiologically, the presence of hilar
      adenopathy was more significant among patients with MTB than those with NTM (17%
      versus 4%, p=0.02). However, bronchiectatic changes were seen significantly more
      among NTM patients compared to patients with MTB (26% versus 11%, p=0.03).
      CONCLUSION: The isolation of NTM in the mycobacteriology laboratory is high. The
      clinico-radiological features were not sufficiently specific to differentiate
      patients with NTM from patients with MTB. Local studies are needed to explore NTM
      disease in various developing countries and identify the NTM species causing
      infections in non-immunosuppressed patients in each locality.

PMID- 15951865
TI  - Evaluation of 2 real-time PCR assays for the investigation of mecA gene in
      clinical isolates of MRSA in Western Saudi Arabia.
AB  - OBJECTIVE: In diagnostic microbiology laboratories, Methicillin resistant
      Staphylococcus aureus (MRSA) is identified by positive coagulase test and
      positive deoxyribonuclease (DNase) activity followed by demonstration of
      oxacillin resistance on susceptibility testing on agar plate. This usually takes
      an approximately 48-72 hours. The purpose of this study is to evaluate 2 real
      time polymerase chain reaction (PCR) assays for the presence of mecA gene in a
      population of MRSA strains circulating in Jeddah, Western Saudi Arabia, in order
      to determine their usefulness in the speedy diagnosis of MRSA in our clinical
      setting and their contribution to optimal patient management. METHODS: Ninety
      MRSA isolates obtained from clinical samples were identified by using
      conventional methods. They were collected between February 2004 and August 2004,
      from 2 major hospitals in Jeddah; King Abdul-Aziz University Hospital, Jeddah (50
      strains) and King Khalid National Guard Hospital, Jeddah (40 strains). All
      isolates were confirmed as MRSA using Gram stain, catalase and coagulase
      activity, confirmatory DNAse activity and Kirby Bauer disc diffusion method with
      resistance to oxacillin by the agar disc method. The DNA extract was tested by 2
      assays. The first was the commercial IVD Roche kit, which detects the mecA gene
      using the Light Cycler system. The other method employs multiplex PCR which
      detects As442 fragment and mecA optimized for the Smart Cycler system (Cephied).
      The length of time taken to perform the assays was recorded. RESULTS: All
      isolates were positive for Sa442 fragment and the coa gene specific for
      Staphylococcus aureus (S. aureus). However, 88/90 isolates (97.7%) tested were
      positive for mecA gene with both systems. The amplification, detection and
      melting curve analysis took 59.2 minutes for 32 samples on the Light Cycler and
      46.7 minutes for 16 samples on the Smart Cycler. CONCLUSION: The 2 methods
      studied were equally specific and sensitive for the detection of mecA gene in
      confirmed S. aureus isolates and capable of identifying MRSA much earlier than
      conventional methods. The detection of 2 targets in the multiplex PCR assay
      reduces the 2-hour time required for DNase testing and may be used as a primary
      screening test for the detection of MRSA in clinical samples, such as blood
      cultures and sterile body fluids.

PMID- 15951866
TI  - Molecular prevalence of point mutations conferring resistance to clarithromycin
      in Helicobacter pylori in the United Arab Emirates.
AB  - OBJECTIVE: The aim of the study was to find the prevalence of point mutations
      conferring resistance to clarithromycin in Helicobacter pylori (H. pylori) in the
      United Arab Emirates. METHODS: Gastric biopsy samples were obtained from 9
      dyspeptic patients attending the endoscopy department in Zayed Military Hospital,
      Abu-Dhabi, UAE during the period from January to September 2004. Real-time
      polymerase chain reaction (PCR) was carried out for these biopsies to determine
      the point mutations. RESULTS: Of the 55 (60%) real-time biopsies that were PCR
      positive for H. pylori, 36 (65.5%) were found to have mutant genes. The
      A(2142/43)G mutation was more common (63.6%) than the A(2142)C mutation (18.2%).
      CONCLUSION: Point mutations A(2442/43)G and A(2142)C and the combination of both
      were common among our patients. Perhaps the highest reported yet. Mutation at
      A(2142/43)G is far more common than mutation at A(2142)C.

PMID- 15951867
TI  - Antibacterial activity of Omani honey alone and in combination with gentamicin.
AB  - OBJECTIVE: To investigate the anti-Staphylococcal activity of Omani honey,
      gentamicin and combination of the 2. METHODS: This study was conducted in the
      Laboratories of the Department of Microbiology and Immunology, College of
      Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman in
      2004. Thirty honey samples from different parts of Oman were investigated for
      their activity against Staphylococcus aureus, using an agar well diffusion
      technique. The honey sample giving the best anti-staphylococcal activity was
      selected and further investigated for the killing rate on its own and in
      combination with gentamicin using tube dilution technique. RESULTS: Marked
      variations in the antibacterial activity of the different honey samples were
      observed. Thirteen of the Omani honey samples (43%) showed excellent anti
      Staphylococcus aureus activity. The best of the excellent honey samples (OH26),
      at a concentration of 50%, showed killing rate of 38% of Staphylococcus aureus at
      30 minutes and 45% at one hour. Gentamicin (at 4 microg/ml) killed 70% and 88%
      while the rate of killing for the combination of honey and gentamicin was
      superior with 92% and 93% killing in the same duration. CONCLUSION: Omani honey,
      in-vitro, possess anti-Staphylococcus aureus activity, which enhances gentamicin
      activity by 22% in the early phases of interaction.

PMID- 15951868
TI  - Animal bites.
AB  - OBJECTIVE: The aim of this study was to put forward a retrospective analysis of
      animal bites treated in our department. METHODS: A total of 1315 patients treated
      in the Department of Plastic Reconstructive and Aesthetic Surgery of Ankara
      Education and Research Hospital, Ankara, Turkey between January 2002 and March
      2004 are included in the study. The fundamental treatment approaches were;
      copious saline irrigation, attentive debridement, appropriate antibiotic
      protocol, elevation and immobilization. RESULTS: Bites were produced by tamed
      (23.4%) and untamed animals (76.6%). The mostly encountered bites were from dogs
      (76.2%) followed by cats (21.7%). The injury sites were mostly in the lower
      (35.0%) and upper (33.0%) extremities. Overall infection rate was found to be 4%
      which were mainly due to cat bites. A very low infection rate (0.03%) was found
      in the group of patients who did not receive prophylaxis. CONCLUSION:
      Prophylactic antibiotics are recommended for severe injuries. Deep, dirty and
      defective injuries should be treated with delayed reconstruction. The majority of
      animal bite injuries in our country are consequence of untamed dogs and cats. The
      excessive lower extremity injuries can be attributed to this fact.

PMID- 15951869
TI  - A new era in laparoscopic surgery. Evaluation of robot-assisted laparoscopic
      procedures.
AB  - OBJECTIVE: To present the experience with the advanced technology of robot
      assisted laparoscopic surgery at our institute. METHODS: We reviewed and present
      patients who had robot-assisted laparoscopic surgical procedures, between April
      2003 and March 2004, at King Khalid University Hospital, Riyadh, Kingdom of Saudi
      Arabia. All procedures were carried out using the da Vinci system (Intuitive
      Surgical, Mountain View, Ca, USA). We recorded the time for system setup,
      operating time, morbidity and postoperative hospital stay. RESULTS: We performed
      42 robot-assisted laparoscopic operations. The most frequently performed
      operations were robot-assisted cardiac procedures (n=25), laparoscopic
      cholecystectomy (n=9) other operations were: thymectomy (4), apical bullectomy
      (2), and one for each adrenalectomy, and lung volume reduction. The median time
      to install and drape the robotic system was 15 minutes. In 2 patients (4.7%) we
      converted the procedures to conventional laparoscopy or open. There was
      postoperative wound infection at the site of the port in one patient. The average
      postoperative hospital stay was similar to conventional laparoscopic procedures.
      CONCLUSION: Robot-assisted minimally invasive surgery is feasible, safe and may
      become the surgical procedure of the future.

PMID- 15951870
TI  - Gastroesophageal reflux following repair of esophageal atresia and
      tracheoesophageal fistula.
AB  - OBJECTIVE: This study represents the experience of a tertiary care center in the
      Kingdom of Saudi Arabia (KSA) on the long-term effect on the lungs of esophageal
      atresia (EA) and tracheoesophageal fistula repair (TEF), and to emphasize the
      magnitude of gastroesophageal reflux (GER) post-EA or post-TEF repair. METHODS: A
      retrospective review of all patients referred to the pulmonary clinic with EA/TEF
      or re-operative evaluations from the period 1993-2004 at King Faisal Specialist
      Hospital and Research Centre, Riyadh, KSA. RESULTS: Forty-one patients with
      confirmed EA/TEF (26 males and 15 females) were included in the study. Congenital
      anomalies were associated in 28 (68%). Gastroesophageal reflux developed in 39
      (95%) of patients, 24 (59%) needed Nissen fundoplication. Esophageal stricture
      that required more than 3 dilations developed in 16 (46%) patients, esophageal
      dysmotility in 37 (90%) and hiatal hernia in 11 (27%). Pulmonary complications
      developed in >70% of the patients including persistent atelectasis, chronic
      aspiration pneumonia, asthma and chronic lung disease that required oxygen for
      more than one month. Tracheomalacia in 12 (29%) and bronchiectasis in 7 (17%).
      Eighty-eight percent of patients who were able to do pulmonary function test
      showed abnormal values of moderate obstructive and restrictive lung disease.
      CONCLUSION: Pulmonary complications cause significant and prolonged morbidities
      post EA/TEF repair. Gastroesophageal reflux is a common complication after EA/TEF
      repair and causes significant morbidity that needs a prolonged follow up.
      Patients with GER may need Nissen fundal plication to improve respiratory
      problems.

PMID- 15951871
TI  - The determination of insulin sensitivity in hemodialysis and continuous
      ambulatory peritoneal dialysis in nondiabetic patients with end-stage renal
      disease.
AB  - OBJECTIVE: To determine the beta-cell function and insulin sensitivity with
      homeostasis model assessment (HOMA) and area under curve (AUC) in nondiabetic
      uremic hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD)
      patients cross sectionally. METHODS: The study was performed between January to
      August 2001 in the Department of Nephrology, Dicle University School of Medicine,
      Diyarbakir, Turkey. Fifty-one HD patients, 45 CAPD patients, and 50 healthy
      control subjects were included in the study. Height, weight, waist and hip
      circumference, fat mass and percentage of body fat, and body mass index (BMI)
      were measured. The total high density lipoprotein (HDL) and low density
      lipoprotein (LDL)-cholesterol, triglyceride, urea, creatinine, insulin,
      potassium, parathyroid hormone (PTH) and 1,25 dihydroxycholecalciferol levels
      were measured. Oral glucose tolerance test (OGTT) was performed in the mid-week
      dialysis-free interval in HD patients, whereas after at least a night without
      dialysis exchanges in CAPD group. Area under curve both of insulin and glucose
      were calculated. The HOMA [insulin sensitivity (%S)] and AUC were used as indices
      of tissue insulin sensitivity. RESULTS: The LDL-cholesterol levels of patients
      with CAPD was higher than the HD group (p<0.001) and control group (p<0.0001).
      The baseline glucose levels of the 2 groups were not significantly different.
      Baseline insulin levels of CAPD group were higher than the HD group (p<0.001) and
      the control group (p<0.0001). Area under curve for glucose (AUCgluc) and insulin
      (AUCins) value of CAPD patients were higher than the HD patients than the control
      group (p<0.0001). The HOMA [beta-cell function (%B)] values of CAPD group were
      higher than both HD (p<0.02) and control group (p<0.04). The HOMA [insulin
      sensitivity (%S)] levels of CAPD group was significantly lower than the HD
      patients (p<0.002) and the control group (p<0.001). CONCLUSION: The CAPD
      treatment may lead to insulin insensitivity in non-diabetic end-stage renal
      disease patients and the high glucose content of CAPD solutions may be
      responsible for insulin resistance in CAPD patients.

PMID- 15951872
TI  - The effect of acute normovolemic hemodilution and acute hypervolemic hemodilution
      on coagulation and allogeneic transfusion.
AB  - OBJECTIVE: In this study, acute normovolemic hemodilution (ANH) and hypervolemic
      hemodilution (HHD) were compared with no hemodilution with regards to the
      effectiveness in blood usage and coagulation parameters. METHODS: The study was
      performed from February to August 2001 at Hacettepe University Hospital, Ankara,
      Turkey. Thirty patients undergoing hip arthroplasty surgery were prospectively
      randomized into: ANH group [autologous blood 15 mL kg(-1) was withdrawn and
      replaced by 6% hydroxyethylstarch (HES)] or HHD group (HES was administered
      without removal of any autologous blood) or the control group (no hemodilution).
      In all groups, blood was given when hemoglobin concentration was <9 g dl(-1).
      RESULTS: Three groups were clinically similar regarding blood loss, mean arterial
      pressures and coagulation parameters. But allogeneic transfusion requirements
      were significantly less in hemodilution groups (20% in ANH, 40% in HHD) compared
      to the control group (100% of patients). CONCLUSION: We conclude that
      hemodilution (both ANH and HHD) decreases the demand for homologous blood without
      adversely affecting hemodynamics or coagulation parameters and HHD seems to be a
      simple and valuable alternative to ANH in orthopedic patient undergoing hip
      replacement.

PMID- 15951873
TI  - Decreased proinflammatory cytokine production by peripheral blood mononuclear
      cells from vitiligo patients following aspirin treatment.
AB  - OBJECTIVE: Limited studies have shown that treatment of cells with aspirin
      modulates their cytokine production. Consequently, the aim of the present study
      is to investigate the pattern of important proinflammatory cytokines production
      by stimulated peripheral blood mononuclear cells (PBMC) from patients with active
      vitiligo following long-term treatment with low-dose oral aspirin. METHODS: The
      study was conducted at the Vitiligo Unit, King Abdul-Aziz University Medical
      Center, Jeddah, Kingdom of Saudi Arabia between March and October 2003. Thirty
      two patients (18 females and 14 males) with non-segmental vitiligo were divided
      into 2 equal groups, one group received a daily single dose of oral aspirin (300
      mg) and the other group received placebo for a period of 12 weeks. The
      concentrations of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor
      alpha (TNF-alpha) were determined in the supernatant of isolated cultured PMBC
      after being stimulated with bacterial lipopolysaccharide (LPS), before the start
      of aspirin treatment and at end of treatment period. Cytokine levels were
      measured using the quantitative sandwich enzyme-linked immunosorbent assay
      (ELISA) technique, utilizing commercially available kits. RESULTS: The
      proinflammatory cytokine production by the PBMC of patients with active vitiligo
      was significantly increased compared to normal controls. Thus, the relative
      percentage increase in the production of IL-1beta, IL-6, IL-8 and TNF-alpha was:
      39.4%, 110.5% (p<0.05), 91.5% (p<0.01), and 37% (p<0.05). At the end of
      treatment, proinflammatory cytokine production in the aspirin-treated group of
      active vitiligo patients was significantly decreased compared to the placebo
      group. Thus, the relative percentage decrease in the production of IL-1beta IL-6,
      IL-8 and TNF-alpha was: 42.5%, 45.2% (p<0.05), 30.8% (p<0.01), and 50.6%
      (p<0.05). The vitiligo activity was arrested in all aspirin-treated patients,
      while 2 patients demonstrated significant repigmentation. CONCLUSION: Chronic
      administration of low-dose oral aspirin can down-regulate the PBMC
      proinflammatory cytokine production in active vitiligo with concomitant arrest of
      disease activity.

PMID- 15951874
TI  - Establishment of a course for Focused Assessment Sonography for Trauma.
AB  - OBJECTIVE: Focused Assessment Sonography for Trauma (FAST) is not widely
      practiced by Trauma Surgeons in the Middle East despite its international
      acceptance. A FAST course was established by the Trauma Group at the Faculty of
      Medicine and Health Sciences at United Arab Emirates (UAE) University aiming to
      introduce doctors who have limited experience of ultrasound to the basics of
      FAST. This article summarizes the content of the course; the evaluation of the
      participants and their recommendations. METHODS: An 8 hour FAST course was
      offered to 18 participants in May 2004 in the Faculty of Medicine and Health
      Sciences, UAE University, Al-Ain, UAE. Lectures with syllabus material were used
      to cover the following topics: basic ultrasound physics, knobology and
      sonographic orientation, the FAST scan, chest and cardiac trauma sonographic
      evaluation, training and credentialing issues. Each participant received 3 hours
      of hands-on ultrasound instruction. On completion of the course participants
      responded anonymously to an evaluation questionnaire. RESULTS: All participants
      responded to the questionnaire (100% response rate). Delegates found the course
      well organized, relevant, met their needs and encourages them to use FAST in
      their own practice. The course objectives were met. Participants suggested that
      including actual patients and the use of animal models improve the practical
      sessions. CONCLUSION: Organizing a FAST course is an important step towards
      recognizing and implementing it in practice. Nevertheless, there is a need for
      appropriate quality assurance and credentialing guidelines before commencing.

PMID- 15951875
TI  - Exploring public knowledge and attitudes towards HIV/AIDS in Saudi Arabia. A
      survey of primary health care users.
AB  - OBJECTIVE: To assess the knowledge and attitudes towards HIV/AIDS among the
      general public in Riyadh city, Saudi Arabia. METHODS: The study employed self
      administered questionnaires to collect data from individuals aged 15 years or
      older who attended Primary Health Centers (PHC) in Riyadh City. In addition to
      demographic characteristics, the questionnaire was designed to collect data on a
      number of statements including basic knowledge about HIV/AIDS, its mode of
      transmission and people's attitudes and source of information about the disease.
      The questionnaires were distributed randomly to 500 persons (250 males and 250
      females) during November and December 2004. Data were analyzed in a descriptive
      fashion. RESULTS: Although the majority of respondents correctly identified the
      main modes of HIV/AIDS transmission, there is a relative deficiency in their
      knowledge about the disease. Moreover, their attitudes towards HIV/AIDS and
      infected persons were defective. The results indicate that this deficiency in
      knowledge and attitudes was associated with some of their demographic
      characteristics such as their gender, level of education, ages and nationality.
      Furthermore, the results show that the contribution of health staff and
      educational institutions was limited in providing the public with information
      about this health problem. CONCLUSION: Although the prevalence of HIV/AIDS in
      Saudi Arabia is low, health care providers in general, and PHC centers in
      particular, should be involved in intensive educational programs as a part of
      their professional mission to help the general public acquire appropriate
      knowledge and attitudes towards HIV/AIDS. This will help in preventing the spread
      of this health problem.

PMID- 15951876
TI  - Profile of viral hepatitis patients in Dakhliya, Oman.
AB  - OBJECTIVE: With the availability of routine serological diagnosis of all the
      major forms of viral hepatitis, namely, A, B, C, D, E consequent to initiation of
      National Viral Hepatitis Surveillance, the twin objective of the study was to
      assess the trend of various types of viral hepatitis and analyze the profile of
      the patients in the region of Al Dakhliya. METHODS: A one year prospective
      cohort, of all the suspects of viral hepatitis enrolled from 01/08/2003 to
      31/07/2004 involving all health facilities (a total of 18 health institutions) of
      Dakhliya region, Sultanate of Oman, was subjected to centralized laboratory
      confirmation. Notification of viral hepatitis confirmed cases was the tool for
      analysis. A subset of unconfirmed viral hepatitis cases that were admitted and
      discharged from the referral hospital were retrieved and analyzed utilizing their
      computerized hospital records. RESULTS: There was a shift of incidence of
      hepatitis B towards higher age groups (32.4 +/- 16.2 years) with only one case
      under 15 years of age (p<0.0001). While as under 15 year age group was less prone
      to hepatitis C (p<0.05), it had a high incidence for hepatitis A with mean age
      11.4 +/- 13.9 years (p<0.01). Hepatitis E incidence had a higher mean age of 44.6
      +/- 24.1 years with insignificant linear trend (p>0.05). CONCLUSION: Progress in
      decline of viral hepatitis B has occurred at a rapid pace during the last decade
      following successful intervention of immunization against hepatitis with an
      almost 100% coverage. Affliction of younger age groups to hepatitis A is
      indicative of continued transmission of the disease in the community demanding
      improvements in preventive practices to curb any impending outbreak.

PMID- 15951877
TI  - Obesity in Saudi Arabia.
AB  - OBJECTIVE: Obesity and overweight are well known risk factors for coronary artery
      disease (CAD), and are expected to be increasing in the Kingdom of Saudi Arabia
      (KSA) particularly among females. Therefore, we designed this study with the
      objective to determine the prevalence of obesity and overweight among Saudis of
      both gender, between the ages of 30-70 years in rural as well as in urban
      communities. This work is part of a major national project called Coronary Artery
      Disease in Saudis Study (CADISS) that is designed to look at CAD and its risk
      factors in Saudi population. METHODS: This study is a community-based national
      epidemiological health survey, conducted by examining Saudi subjects in the age
      group of 30-70 years of selected households over a 5-year period between 1995 and
      2000 in KSA. Data were obtained from body mass index (BMI) and were analyzed to
      classify individuals with overweight (BMI = 25-29.9 kg/m2), obesity (BMI >/=30
      kg/m2) and severe (gross) obesity (BMI >/=40 kg/m2) to provide the prevalence of
      overweight and obesity in KSA. RESULTS: Data were obtained by examining 17,232
      Saudi subjects from selected households who participated in the study. The
      prevalence of overweight was 36.9%. Overweight is significantly more prevalent in
      males (42.4%) compared to 31.8% of females (p<0.0001). The age-adjusted
      prevalence of obesity was 35.5% in KSA with an overall prevalence of 35.6% [95%
      CI: 34.9-36.3], while severe (gross) obesity was 3.2%. Females are significantly
      more obese with a prevalence of 44% than males 26.4% (p<0.0001). CONCLUSION:
      Obesity and overweight are increasing in KSA with an overall obesity prevalence
      of 35.5%. Reduction in overweight and obesity are of considerable importance to
      public health. Therefore, we recommend a national obesity prevention program at
      community level to be implemented sooner to promote leaner and consequently
      healthier community.

PMID- 15951878
TI  - Epidemiology of urinary incontinence in Jordanian women.
AB  - OBJECTIVE: To find out prevalence rate of urine incontinence (UI) in a
      representative sample of women aged 50-65 years in south Jordan. The study will
      also investigate the relationship between UI (stress and urge) and the following
      variables: age of the woman and her parity, diabetes mellitus, urinary tract
      infection (UTI), body mass index (BMI), medications (diuretics), menopause, past
      history of hysterectomy, and poor mobility. METHODS: For achieving the objectives
      of this study, a sample of women (n=182) in the age group 50 - 65 years in south
      Jordan (Karak, Taffileh, Aqaba) was selected using a multistage sampling
      procedure to represent women in this age group in south Jordan. A questionnaire
      and face-to-face interviews were used as the instrument for data collection. The
      questionnaire was tested in a pilot study before starting data collection from
      the field. Data was collected from the field in July 2003. Data was analyzed
      using Statistical Package for Social Science (SPSS). Chi Square Test and Fisher's
      Exact Probability Test were used to identify the significance of associations
      between UI and characteristics of the respondents. RESULTS: Approximately one
      third of respondents had urinary incontinence; 23.1% had stress UI, 26.4% had
      urge UI, and 18.1% had the mixed type. Prevalence rate of UI was 56.3% for women
      suffering from UTI and 50% for those who use diuretics. Approximately 54% of
      women who need help to go around inside the house were complaining of UI. High
      prevalence rates were also observed if parity was 5 - 6 (43.5%), women at
      menopause (39.7%), obese women (39.3%), and in diabetic women (35%). High
      prevalence rates of stress incontinence were found in women suffering from UTI
      (37.5%), in women using diuretics (39.5%), if parity was 5 - 6 (34.8%), and in
      women with past history of hysterectomy (28.6%). Stress UI was increasing with
      the increase in the BMI. The associations between urge incontinence, BMI, UTI,
      use of diuretics, and the ability to go around inside the house were all
      significant at the 0.05 level. CONCLUSION: Prevalence rate of UI varied from one
      country to another and from one study to another study. Possible reasons for such
      inconsistency were discussed. Appropriate treatment of UI should be based on
      valid diagnosis of cases, type of UI, and the identification of contributing
      factors. Lines of treatment and interventions for UI were discussed. Further
      studies of this condition are needed in Jordan for both males and females and in
      all age groups. Such studies should emphasize the size of the problem, etiology
      and risk factors, and the cost of the problem for both the incontinent person and
      for the health care system.

PMID- 15951879
TI  - Visual disabilities among diabetics in Oman.
AB  - OBJECTIVE: The magnitude, determinants of visual impairment, bilateral blindness
      and low vision among diabetics in Oman were estimated as part of Oman Diabetic
      Eye Study 2002. This study presents the outcomes and additional risk of visual
      impairment in diabetics. METHODS: A cross-sectional study of 2,520 randomly
      selected diabetics was conducted in 2002 in 10 regions of Oman. The sample was
      represented by 5,564 diabetics referred for eye checks. Ophthalmologists noted
      the vision and ocular manifestations of diabetes. Physicians reported the
      systemic manifestations of diabetes. The magnitude of visual disabilities,
      bilateral blindness, legal blindness and low vision were estimated and compared
      to the rates in the population. RESULTS: The prevalence of visual impairment in
      diabetics was 28.4% (95% confidence interval [CI] 27.20-29.57). It was 34.6% (95%
      CI 32.93 to 36.32) in females and 21.2% (95% CI 19.59 to 36.32) in males. The
      prevalence increased in age. The prevalence of bilateral blindness (vision <0.05)
      was 0.7%, legal blindness 9.8% (vision <0.1) and low vision 27.7% (vision <0.5).
      CONCLUSION: The risk of visual impairment is 25 times more in diabetics than in
      the Omani population. Therefore, to prevent further increase of visual
      disabilities, the national health program should prioritize the eye care in
      diabetics and the predictors of visual disabilities should be further
      investigated.

PMID- 15951881
TI  - A regression equation to predict true maximal oxygen consumption of taekwondo
      athletes using a field test.
AB  - OBJECTIVE: The purpose of the present study was to examine the validity of using
      a 20 meter multistage shuttle run test to estimate maximal oxygen uptake.
      METHODS: Twenty-two elite taekwondo athletes (11 male, 11 female, members of the
      Turkish young national team), participated in the study. The respiratory gas
      exchange parameters were measured using portable gas analysis system while
      shuttle run test was carried out. All tests were performed last August 2004, in
      the gymnasium of Suleyman Demirel University, Isparta, Turkey. RESULTS: Analysis
      of the test scores showed a mean score on gas analysis of 51.79 ml/kg/min and a
      mean score of 43.59 ml/kg/min on the shuttle run test. On average, the scores
      predicted by the shuttle run test were 16% lower than those for the gas analysis
      score. The correlation between the tests was significant at a level of r = 0.810.
      CONCLUSION: Maximal oxygen consumption (VO2 max) can be predicted from shuttle
      run test scores, but not as indicated with the test package. In order to obtain
      the true score one must apply a regression equation.

PMID- 15951880
TI  - Comparison of supervised exercise training and home-based exercise training in
      chronic heart failure.
AB  - OBJECTIVE: This study was planned to compare the outcomes between supervised and
      home-based exercise training in patients with chronic heart failure. METHODS: The
      study was conducted at the Department of Physical Therapy in Ankara University,
      Faculty of Medicine, Turkey between 2000 and 2001. Twenty-two patients with
      stable chronic heart failure were randomly assigned to the supervised exercise
      training group (n=11) or the home-based exercise training group (n=11). Symptom
      limited maximal exercise tests with gas exchange analysis were carried out before
      randomization. Work load equivalent to 60% of achieved peak heart rate at the
      tests was determined as exercise training work load for each subject. Both groups
      participated in a program of 3 exercise training sessions per week for 3 months.
      The exercise tests were repeated after 3 months. RESULTS: After training, peak
      exercise duration increased significantly in the supervised exercise training
      group and the home-based exercise training group (p<0.05). There was substantial
      improvement in peak VO2 with exercise training in the supervised exercise
      training group (p<0.05) but, peak VO2 did not change significantly in the home
      based exercise training group (p>0.05). CONCLUSION: Supervised and home-based
      exercise training enhanced exercise capacity in patients with chronic heart
      failure. The training program must be tailored to each patient's specific
      limitations, individual needs and possibilities. Home-based exercise training may
      be a training alternative to stable chronic heart failure patients who prefer not
      to participate in an outpatient supervised training program.

PMID- 15951882
TI  - An evaluation of the variation in the rates of occupational accidents in Turkey
      with trend analysis methodology. Are occupational accidents really diminishing?
AB  - OBJECTIVE: To show whether the rate of occupational accidents is decreasing in
      Turkey. METHODS: Data on incidence and deaths due to occupational accidents in
      Turkey during the period 1970-2000 were obtained and evaluated at the Department
      of Public Health, Hacettepe University, Ankara, Turkey. The data were collected
      in January 2003. The occupational accident rates were analyzed by morbidity,
      mortality and case fatality rates. The change in each variable over years was
      tested by trend analysis methodology. A regression analysis was performed on data
      on 3-point moving averages. RESULTS: The morbidity decreases significantly over
      the last 30 years (p<0.01) with a slope of -0.003. The correlation of the
      morbidity tendency due to years was 0.995 (p<0.01) and the total variance
      descriptive rate was 0.991. In respect to mortality, the variation due to years
      was declining (0.00001, p<0.01). The correlation of the model was 0.950 (p<0.01)
      and brings out the total variance to 0.903. The trend analysis model can be
      explained meaningfully in respect of constant and slope (p<0.01). In respect of
      fatality the variance over the years was 0.00029 (p<0.01). The correlation of the
      model was 0.934 (p<0.01) and brings out the total variance of 0.872. CONCLUSION:
      The main reason of the decrease of occupational accidents was probably due to
      unreported accidents, which do not cause injury. Reasons for underreporting of
      minor accidents should be investigated and this point should be taken into
      consideration when planning an occupational accident prevention programs.

PMID- 15951883
TI  - Scanning electron microscopic observation of the brown tumor of the head of
      mandible.
AB  - Brown tumors are tumor-like, expansile osteolytic lesions of bone which are seen
      in both primary and secondary hyperparathyroidism. They generally resolve after
      surgical treatment of the parathyroid adenoma. Here, we report a case of brown
      tumor of the mandible of a cadaver with its scanning electron microscopic
      observation and review of literature.

PMID- 15951884
TI  - Malignant eccrine poroma.
AB  - Benign eccrine poroma arises from the intraepidermal portion of the eccrine gland
      duct. Malignant transformation is rare and should be suspected when these lesions
      present with pain, bleeding or itching. We report a 44-year-old male patient who
      presented primarily with a lesion diagnostic of benign eccrine poroma of the
      right foot sole with no clear evidence of malignancy, which was incompletely
      excised, followed 5 months later by local recurrence, ulceration, occasional
      bleeding and right inguinal lymphadenopathy. Incomplete excision of the primary
      tumor as well as excision of a skin lesion on the right knee joint revealed
      malignant eccrine poroma with aggressive histology, lymphovascular and perineural
      invasion. Investigations revealed no evidence of distant metastasis. This tumor
      might be malignant at the first presentation, which was not confirmed
      histopathologically considering the short duration of only 5 months for malignant
      transformation. The patient received 3 cycles of Docetaxel Taxotere, Cisplatin
      combination chemotherapy with partial response. The management of metastatic
      malignant eccrine poroma is difficult. It has proven resistant to many
      chemotherapeutic agents and radiotherapy.

PMID- 15951885
TI  - Klippel-Feil syndrome with associated agenesis of lung and gall bladder
      presenting with asthma and allergic rhinitis.
AB  - Klippel-Feil syndrome KFS, a triad of short neck, limitation of neck movement and
      low posterior hairline, is characterized by presence of congenitally fused
      cervical vertebrae and is often associated with multiple congenital anomalies. A
      35-year-old male was referred for evaluation of an opaque hemithorax. This led to
      a diagnosis of KFS, agenesis of left lung and gall bladder. The patient had
      history of wheezing dyspnea with nasal symptoms, which were diagnosed as asthma
      and allergic rhinitis. A high index of suspicion is required to recognize such a
      patient, and efforts should be made to seek other congenital anomalies.

PMID- 15951886
TI  - Intralobar pulmonary sequestration presenting as a large multicystic mass.
AB  - A large multicystic mass lesion is not a common presentation of pulmonary
      sequestration. This presentation may result in failure to identify the supplying
      systemic artery due to multiplicity of the large cysts and, therefore, a wrong
      diagnosis. We discuss a case of intralobar pulmonary sequestration presented
      similarly. Chest x-ray and CT appearance gave an initial impression of hydatid
      disease which is endemic in Saudi Arabia. Fortunately, the supplying systemic
      artery was identified in the final CT review before surgery. Preoperative correct
      diagnosis of pulmonary sequestration is important to plan the appropriate surgery
      and to prevent possible intractable intraoperative hemorrhage. Awareness of this
      uncommon presentation of pulmonary sequestration helps to prevent such a fatal
      complication.

PMID- 15951887
TI  - Congenital varicella-zoster virus infection. A rare case of severe brain and
      ocular malformations without limb or cutaneous involvement in a newborn after
      maternal subclinical infection.
AB  - Although congenital varicella-zoster virus VZV infection is rare, it carries
      serious morbidity and mortality to the fetus and newborn infant. We report a full
      term female newborn infant, born to a multipara unbooked mother who had VZV
      subclinical infection during the first trimester of pregnancy. Routine newborn
      examination showed cystic malformation of the left eye, and absence of the right
      eye globe. Radiological work up revealed severe brain and eye malformations,
      serological studies of both mother and baby were positive for VZV. The baby
      underwent palliative surgery to the eyes, upon discharge, a plan of
      multidisciplinary team was made for follow up including neurologist,
      ophthalmologist, pediatrician and social worker. Congenital VZV infection can be
      severe enough to cause catastrophic fetal anomalies and damage to the vital
      organs as many of those infants die in infancy.

PMID- 15951888
TI  - Familial dysgerminoma associated with 46, XX pure gonadal dysgenesis.
AB  - Although the occurrence of pure gonadal dysgenesis PGD is usually sporadic and
      nonfamilial, here we present 3 sisters with 46, XX PGD, who are born from a first
      cousin marriage. Review of their family pedigree is compatible with autosomal
      recessive inheritance. Surprisingly, 2 of these sisters developed ovarian tumors.
      Both showed the pathological result of dysgerminoma with syncytiotrophoblastic
      giant cells. These 2 cases are examples of tumorigenesis in PGD without an
      identifiable Y chromosome. Therefore, malignant degeneration of the streak gonads
      should be considered in the patients with 46, XX PGD.

PMID- 15951889
TI  - Cockayne syndrome in 2 siblings.
AB  - Cockayne syndrome is a rare autosomal recessive condition characterized by growth
      failure and multisystem progressive degeneration. We report and describe this
      syndrome in a Jordanian brother and sister with Cockayne syndrome with first
      cousin parents. Clinical features included short stature, cachectic senile look,
      neurological deterioration, photosensitivity, mental retardation, hearing
      impairment and carious teeth. The phenotype is compatible with a mild variant of
      type I Cockayne syndrome. They showed an exaggerated response to growth hormone
      provocation test, with slightly elevated basal insulin-like growth factor 1
      levels. The radiological findings of thinning of ribs and slender femora with
      narrow medullary canals have not previously been reported in this syndrome. We
      discuss the implications of these findings.

PMID- 15951890
TI  - Coronary artery anomaly.

PMID- 15951891
TI  - Do mobile phones cause hearing and vision complaints? A preliminary report.

PMID- 15951892
TI  - Duodeno-jejunal anastomosis with trans anastomotic nasojejunal tube for
      congenital duodenal obstruction.

PMID- 15951893
TI  - The prevalence of Candida dubliniensis among germ tube positive candida samples
      isolated from the respiratory tract.

PMID- 15951894
TI  - Noninvasive ventilation in mild to moderate cases of respiratory failure due to
      acute exacerbation of chronic obstructive pulmonary disease.

PMID- 15951895
TI  - Stressors and coping strategies of medical students. Gender differences.

PMID- 15951896
TI  - Smoking habits among pharmacy students at a University in central Saudi Arabia.

PMID- 15951897
TI  - Clinical growth charts for pre-school children.

PMID- 15951898
TI  - Enhancing biomedical research in Saudi Arabia.

PMID- 15951899
TI  - [Small for gestational age: severity, proportionality and risk of mortality].

PMID- 15951900
TI  - [The prevalence of hepatitis A antibodies in HIV exposed and/or infected children
      and adolescents].

PMID- 15951901
TI  - [The challenge of diagnosing dengue in children].

PMID- 15951902
TI  - [The safety of nebulization with 3 to 5 ml of adrenaline (1:1000) in children: an
      evidence based review].
AB  - OBJECTIVE: To present the evidence regarding the safety of nebulization with 3-5
      ml of adrenaline (1:1000) for the treatment of children with acute inflammatory
      airway obstruction. SOURCES OF DATA: An electronic search was undertaken, using
      mainly Medline databases (January of 1949-July of 2004). The study inclusion
      criteria for this review were: 1) randomized clinical trial; 2) Patients (up to
      12 yrs) with diagnosis of bronchiolitis or laryngotracheobronchitis; 3) use of
      adrenaline (1:1000) by nebulization. The principal data extracted from the trials
      included adrenaline dosages and their effects on heart rate and blood pressure
      and any other side-effects. SUMMARY OF THE FINDINGS: Seven clinical trials with a
      total of 238 patients were included for this review. Two of the five trials in
      which larger dosages (> or = 3 ml) of adrenaline were used demonstrated a
      significant increase in heart rate. The mean increase in heart rate varied from
      seven to 21 beats per minute, up to 60 minutes after treatment. The highest
      incidence of pallor was observed in one trial with 21 children treated by
      nebulization with 3 ml of adrenaline (47.6% in the adrenaline group vs. 14.3% in
      the salbutamol group, 30 minutes after treatment). Two clinical trials failed to
      observe a significant effect on blood pressure from nebulization with adrenaline
      (4 and 5 ml). CONCLUSION: Evidence shows that nebulization with 3 to 5 ml of
      adrenaline (1:1000) is a safe therapy, with minor side-effects, for children with
      acute inflammatory airway obstruction.

PMID- 15951903
TI  - [An assessment of the severity, proportionality and risk of mortality of very low
      birth weight infants with fetal growth restriction. A multicenter South American
      analysis].
AB  - OBJECTIVES: To evaluate the clinical severity and proportionality of small for
      gestational age, very low birth weight neonates (< 1,500 g) and to estimate the
      neonatal mortality risk associated with the condition of being small for
      gestational age according to the degree of severity and proportionality. METHODS:
      Observational design. All of the NEOCOSUR Collaborative Group's very low birth
      weight infants (25-36 weeks' gestation) were included (n = 1,518). Anthropometric
      indices: birth weight < 3rd and 10th percentile. Severity (fetal growth ratio =
      observed weight/mean birth weight for gestational age); no growth restriction:
      fetal growth ratio 0.90-1.10, mild: fetal growth ratio 0.80-0.89, moderate: fetal
      growth ratio 0.75-0.79 and severe: fetal growth ratio < 0.75. Proportionality:
      coefficient of bimodality and z score for ponderal index (PI = g/cm3 x 100).
      Neonatal mortality until discharge. RESULTS: < 3rd percentile: 13.5% (p < 0.001);
      < 10th percentile: 31% (p < 0.001); fetal growth ratio: 0.90-/+0.21 (p < 0.001),
      mild restriction: 20.8%, moderate restriction: 8.7% and severe restriction:
      32.6%. Coefficient of bimodality: 0.53; PI z score < -1: 8%. Maternal
      hypertensive disease was systematically associated with being small for
      gestational age (aOR 1.20, 95% CI 0.86-1.67), fetal growth ratio < or = 0.89 (aOR
      1.71, 1.24-2.36) and PI z score < -1 (aOR 1.60, 1.03-2.41). Adjusted odds ratios
      for neonatal mortality were: 2.64 (95% CI 1.71-3.92) for being small for
      gestational age, 2.76 (95% CI 1.85-4.10) for fetal growth ratio < or = 0.89, and
      1.37 (95% CI 0.80-2.32) for z score PI < -1. CONCLUSIONS: Small for gestational
      age, mostly symmetric and severe restriction is a frequent condition in < 1,500 g
      neonates and is associated with higher mortality rates.

PMID- 15951904
TI  - [The prevalence of hepatitis A antibodies in HIV exposed and/or infected children
      and adolescents].
AB  - OBJECTIVE: To evaluate the prevalence of hepatitis A virus antibodies in HIV
      exposed and/or HIV-infected children and adolescents. METHODS: Between September
      1996 and August 2002, 352 patients (200 exposed, but not HIV-infected and 152 HIV
      exposed and infected) were included in this study. These children and adolescents
      (age ranged between 1 and 14 years) were all followed up at the Pediatric AIDS
      Clinic of the Federal University of Sao Paulo (UNIFESP) and had anti-HAV
      antibodies determined by a commercially available ELISA method (tests for total
      anti-HAV antibodies and specific IgM antibodies) (Dia Sorin and Radim).
      Statistical analyses were done with chi-squared and t test. RESULTS: The
      prevalence of hepatitis A virus antibodies in HIV-infected and HIV-exposed, but
      uninfected patients was 34% and 19.7%, respectively. We noticed that in the age
      range between 2 years and 10 years, the group of HIV-infected children presented
      a higher prevalence of hepatitis A virus antibodies (35.5%) than the group of
      uninfected children (16.7%) (p = 0.005). In the HIV infected group, children from
      B and C categories had a prevalence of hepatitis A virus antibodies (40.5%)
      higher than N and A categories (24.1%) (p = 0.042). Mean age did not differ when
      children from B and C categories were compared with N and A categories (5.18 and
      5.66 years, respectively) (p = 0.617). CONCLUSIONS: The prevalence of hepatitis A
      virus antibodies in HIV exposed and/or infected children and adolescents between
      1 and 14 years old was 26%. Considering the possibility of HIV infection
      aggravation when associated with hepatitis A virus infection, we suggest that
      hepatitis A virus inactivated vaccine should be administered to these patients.

PMID- 15951905
TI  - [Is it possible to identify dengue in children on the basis of Ministry of Health
      criteria for suspected dengue cases?].
AB  - OBJECTIVES: To identify clinical characteristics indicative of dengue and to
      evaluate the applicability to children of the Health Ministry criteria for
      suspected cases. METHODS: A cross-sectional study undertaken at the General
      Pediatrics Center of the Fundacao Hospitalar de Minas Gerais. Children were
      enrolled if presenting acute febrile conditions with no definite etiology,
      lasting > 24 hours and < or = 7 days and if resident in the Metropolitan Region
      of Belo Horizonte. Clinical variables were investigated, specific tests were
      performed and aspartate-aminotransferase assayed, during a period considered both
      endemic and epidemic for the disease. The subset of children who did have dengue
      was compared with the subset of nonspecific acute febrile diseases. The Health
      Ministry criteria for suspected cases was evaluated. RESULTS: Dengue was
      diagnosed in 50.4% of the 117 children studied. There were no statistically
      significant associations between the disease and the majority of the symptoms
      analyzed. Only exanthema was more often associated with dengue (Prevalence Ratio
      = 1.49; 95% CI: 1.05-2.11). The criteria for suspected cases of dengue had a
      sensitivity of just 50.8% and a positive predictive value of 62.5%. These values
      were greater among schoolchildren and during the period of greater disease
      incidence. CONCLUSIONS: Dengue is common among febrile diseases of childhood,
      with prevalence that varies according to the epidemiological situation. The
      clinical status of children with dengue was very similar to that of children with
      other nonspecific diseases. The Health Ministry criteria for suspected cases was
      shown to be of little use, particularly with smaller children and during periods
      of reduced incidence.

PMID- 15951906
TI  - [Induced sputum in children and adolescents with asthma: safety, clinical
      applicability and inflammatory cells aspects in stable patients and during
      exacerbation].
AB  - OBJECTIVES: To determine the safety of sputum induction in asthmatic children and
      adolescents, to characterize sputum inflammatory cells while clinically stable
      and during exacerbation and to correlate sputum inflammatory cells with
      peripheral blood eosinophils, serum IgE and the degree of bronchial obstruction.
      METHODS: Ninety-six asthmatic patients aged 6 to 18 years were recruited for the
      present cross-sectional study. Spirometry was performed before and after
      administration of a bronchodilator. Sputum was collected spontaneously or after
      induction by the inhalation of saline solution at increasing concentrations.
      Blood samples were obtained for serum IgE and eosinophil quantification. RESULTS:
      Sputum samples adequate for analysis were obtained from 68 (70.8%) of the
      patients recruited. No relevant bronchoconstriction was observed during
      induction. The presence of a larger number of eosinophils in sputum did not
      correlate with more clinically severe asthma. No correlation was observed between
      the degree of bronchial obstruction, measured based on FEV1, and inflammatory
      cells in sputum, peripheral blood eosinophils or serum IgE. Larger numbers of
      neutrophils were observed in the asthma exacerbation group (p < 0.05).
      CONCLUSIONS: Sputum induction was found to be a safe procedure for obtaining
      clinical samples from children and adolescents even during exacerbations,
      allowing for clinical and functional limitations. The 67% induction success rate
      was considered satisfactory. In this group of patients, receiving inhaled
      corticosteroids, eosinophil quantification did not distinguish between the
      clinical and functional severity of asthma and was independent of the degree of
      airway obstruction. A proportional predominance of neutrophils was observed in
      the sputum of patients with asthma exacerbation.

PMID- 15951907
TI  - [Investigation of voiding dysfunction in a population-based sample of children
      aged 3 to 9 years].
AB  - OBJECTIVE: To describe voiding patterns and related dysfunctions in a population
      based sample of children aged 3 to 9 years. METHODS: A cross-sectional population
      based survey including 580 children. A probabilistic sample of households in the
      urban area of Pelotas in southern Brazil was selected following a multiple-stage
      protocol. Voiding and fecal patterns were investigated using the dysfunction
      score created by Farhat et al. and modified by the addition of high urinary
      frequency (more than eight times a day). Boys with scores above eight and girls
      above five were clinically investigated, as well as a sub-sample of the remaining
      children. RESULTS: Nocturia (60.4%), urinary urgency (49.7%) and holding
      maneuvers (42.1%) were the most frequently reported symptoms. The prevalence of
      enuresis was 20.1% in boys and 15.1% in girls. The prevalence of urinary
      dysfunction was 22.8%. Most symptoms were more frequently reported by girls and
      younger children. Among girls, low socioeconomic level was related to an
      increased prevalence of enuresis and straining to urinate, while among boys
      urgency was more common among the poor. Only 10.5% of the parents of the children
      with voiding dysfunction consulted a doctor because of their problems.
      CONCLUSIONS: The voiding symptoms studied presented high prevalence rates, and
      therefore should be investigated in clinical practice, with direct questions
      about each symptom, aiming to diagnose voiding dysfunction.

PMID- 15951908
TI  - [Teaching neonatal resuscitation at public hospitals in Brazilian state
      capitals].
AB  - OBJECTIVE: To analyze the teaching of neonatal resuscitation offered by Brazilian
      public hospitals to undergraduate doctors and nurses, pediatric residents and
      neonatal fellows. METHODS: This cross-sectional multicenter study included 36
      hospitals in 20 Brazilian State capitals during June/2003. Local coordinators
      collected data regarding what the institutions offer to undergraduate doctors and
      nurses, pediatric residents and neonatal fellows in terms of neonatal
      resuscitation training and practical activities in neonatal delivery room care.
      Descriptive analysis was performed. RESULTS: Twenty-three of the 36 institutions
      had undergraduate doctors: at 13 of them students had clinical activities in the
      delivery room, 12 offered neonatal resuscitation training, and at two of the 13
      hospitals, interns cared for neonates in the delivery room without specific
      training. Twenty-three of the 36 hospitals had undergraduate nurses: at eight of
      them students had clinical activities in the delivery room and at seven of them
      nursing students cared for neonates in the delivery room without specific
      training. Twenty-seven of the 36 institutions had pediatric residence programs:
      at all of them, trained residents cared for neonates in the delivery room, but
      the training was heterogeneous: theoretical training (2-3 hours) at four
      institutions and theoretical and practical training (4-64 hours) at 23.
      Additionally, 15 had neonatal fellowship programs: at all of these, trained
      fellows cared for neonates in the delivery room, but the training was
      heterogeneous: theoretical training (2 hours) at one hospital and theoretical and
      practical training (3-68 hours) at 14. CONCLUSION: Formal neonatal resuscitation
      training is insufficient during medical and nursing graduation and
      heterogeneously offered to pediatric residents and neonatal fellows.

PMID- 15951909
TI  - [Neonatal cystic fibrosis screening program in the state of Parana: evaluation 30
      months after implementation].
AB  - OBJECTIVES: To present and analyze the results of the National Neonatal Cystic
      Fibrosis Screening Program in Parana, 30 months after its implementation.
      METHODS: This is a descriptive study, with an analysis of the data from the
      screening of around 98% of all neonates in the period from September 2001 to
      April 2004, undertaken at the Neonatal Screening Program laboratory of the
      Fundacao Ecumenica de Protecao ao Excepcional do Parana. Blood samples for the
      Guthrie test were collected on hospital discharge, ideally between the second and
      sixth days postpartum, and filter papers were sent for immunoreactive trypsin
      assay by the immunofluorometric method. Children whose immunoreactive trypsin
      assay results were > or = 70 ng/ml for two distinct samples during the first 30
      days of life, were referred for sweat conductivity testing by the Wescor method.
      In cases when the result was greater than 50 mMol/l quantitative chlorine and/or
      sodium in sweat was assayed (iontophoresis with pilocarpine). RESULTS: From a
      total of 456,982 tests, 4,028 (0.9%) children presented a first immunoreactive
      trypsin assay above the cutoff point set. Four hundred and seventy-eight of these
      (12.5%) also had a second blood sample assayed with immunoreactive trypsin above
      70 ng/ml and 56 (11.7%) of these were referred to specialized clinics after their
      sweat conductivity test results were above 50 mMol/l and 48 (0.01% of the total
      number of children screened) had a diagnosis of cystic fibrosis confirmed. The
      incidence for the state of Parana was 1:9,520, although some children have not
      yet been fully investigated. CONCLUSIONS: Neonatal screening for cystic fibrosis
      in the State of Parana, in accordance with Health Ministry directives, was a
      pioneering initiative for Brazil. Many patients were diagnosed early, even
      asymptomatic ones, which is a challenge to improving prognosis with this fatal
      disease.

PMID- 15951910
TI  - [Evaluation of compliance through specific interviews: a prospective study of 73
      children with acute lymphoblastic leukemia].
AB  - OBJECTIVE: To evaluate compliance in children with acute lymphoblastic leukemia.
      METHOD: Compliance was assessed through specific interviews. RESULTS: A total of
      73 patients who had concluded the maintenance phase of chemotherapy were enrolled
      on the study. Eighty-one percent of the interviews were conducted with the
      patients' mothers; 92% of the families stated that medical instructions had been
      understood well. Interviews indicated that 27% of the patients did not receive
      their medication twice or more during the maintenance phase, without medical
      direction for this. These children were considered non-compliant. Sixteen percent
      of the children failed to receive their medication three times or more. The main
      reason for non-compliance was forgetfulness. In ten cases the reported dosage of
      drugs was not that which was prescribed. No significant associations of non
      compliance with parents' schooling level, number of family members or per capita
      family income were detected. The 8.5-year estimated probability of event free
      survival was 72.4% (95% CI: 59.2-82.3). The event free survival curves for non
      compliant children were not statistically different from those for the compliant
      group. CONCLUSIONS: Results suggest that comprehensive approaches to the problem
      of non-compliance are urgently needed.

PMID- 15951911
TI  - [Access to basic care for children seen at emergency departments].
AB  - OBJECTIVE: To investigate access to basic actions among children attended at
      emergency departments, reconstructing their trajectories to contact with the
      service for the event in question, characterizing links with basic care and the
      appropriateness of morbidity to the organizational profile of the service
      attended. METHODS: Cross-sectional study, carried out in November 2002 and from
      February to May 2003 at five public pediatric emergency services, of a sample of
      383 children under five years old, resident in Recife, calculated for an
      estimated 20% of appropriate morbidity, 5% error and 10% loss. Using standard
      instruments applied by eight purposely-trained interviewers. RESULTS: During
      their trajectories to reach the contact in question, 38.5% of the children had
      sought other services, primarily: emergency (48.3%), family health team (19.7%)
      and health centers (17%), with 18.4% having experienced difficulties with primary
      care. 39.4% only used emergency and at some point 54.4% had resorted to this type
      of service. Approximately 88% are registered with a unit: 34.5% with the family
      health team (56.8% of these didn t use the service and 25.6% had sought them),
      42% at health centers (59.1% of those didn t use the service and 18.2% had
      resorted to them). Only 18.9% preferred a basic unit when their child was ill,
      and therefore for the contact in question, the majority had been brought to their
      preferred service (like/confide in our professionals, geographic accessibility,
      and quality of care). Just 36.5% of the demand was defined as appropriate.
      CONCLUSIONS: Despite of difficulties with the basic network in guaranteeing
      access and resolution, a substantial part of this spontaneous demand came from
      the enormous legitimacy of the emergency services as seen by the population.

PMID- 15951912
TI  - [Comparison of two prognostic scores (PRISM and PIM) at a pediatric intensive
      care unit].
AB  - OBJECTIVE: To compare the performance of the PRISM (Pediatric Risk of Mortality)
      and the PIM (Pediatric Index of Mortality) scores at a general pediatric
      intensive care unit, investigating the relation between observed mortality and
      survival and predicted mortality and survival. METHODS: A contemporary cohort
      study undertaken between 1 June 1999 and 31 May 2000 at the Pontificia
      Universidade Catolica do Rio Grande do Sul, Hospital Sao Lucas pediatric
      intensive care unit. The inclusion criteria and the PRISM and PIM calculations
      were performed as set out in the original articles and using the formulae as
      published. Statistical analysis for model evaluation employed the Flora z test,
      Hosmer-Lemeshow goodness-of-fit test, ROC curve (receiver operating
      characteristic) and Spearman's correlation tests. The study was approved by the
      institution's Ethics Committee. RESULTS: Four hundred and ninety-eight patients
      were admitted to the pediatric intensive care unit, 77 of whom presented
      exclusion criteria. Thirty-three (7.83%) of the 421 patients studied died and 388
      patients were discharged. Estimated mortality by PRISM was 30.84 (7.22%) with a
      standardized mortality rate of 1.07 (0.74-1.50), z = -0.45 and by PIM this was
      26.13 (6.21%) with a standardized mortality rate of 1.26 (0.87-1.77), z = -1.14.
      The Hosmer-Lemeshow test gave a chi-square of 9.23 (p = 0.100) for PRISM and
      27.986 (p < 0.001) for PIM. The area under the ROC curve was 0.870 (0.810-0.930)
      for PRISM and 0.845 (0.769-0.920) for PIM. The Spearman test returned r = 0.65 (p
      < 0.001). CONCLUSION: Analyzing the tests we can observe that, although the PIM
      test was less well calibrated overall, both PRISM and PIM offer a good capacity
      for discriminating between survivors and moribund patients. They are tools with
      comparable performance at the prognostic evaluation of the pediatric patients
      admitted to our unit.

PMID- 15951913
TI  - Bronchopleural cutaneous fistula due to Eikenella corrodens.
AB  - OBJECTIVE: The aim of this paper is to review the subject and to report on and
      discuss a case of bronchopleural cutaneous fistula due to Eikenella corrodens.
      DESCRIPTION: A 16-year-old girl was brought to our hospital with fever and blood
      tinged sputum 2 weeks prior to her admission. She suffered from neurologic
      sequelae of herpetic encephalitis and had been bed-ridden since 5 years of age. A
      longitudinal paraspinal soft mass had been noted in the previous week by her
      mother. She had been given oral feeding despite frequent choking for the past few
      years. On palpation, the mass can be squeezed to follow the least resistance of
      subcutaneous space longitudinally extending to the lower thoracic region. Chest
      computed tomography scan revealed right lower lobe necrotizing pneumonitis and a
      pleuro-cutaneous fistula leading to the subcutaneous air locules. A protracted
      course of antibiotics was prescribed and subcutaneous air trapping decreased in
      size over 8 weeks. COMMENTS: Eikenella corrodens has increasingly been implicated
      as a potential causative pathogen in pleuropulmonary infections. Pleuro-cutaneous
      fistula and abscess formation complicating empyema and necrotizing pneumonitis
      due to E. corrodens infection have not been reported. A bulging thoracic
      subcutaneous lesion waxes and wanes with respiration suggest the possibility of a
      pleruo-cutaneous fistula. Treatment of Eikenella empyema using antibiotics
      without surgical decortication requires a prolonged course of antibiotic therapy.

PMID- 15951915
TI  - [Evaluation of weight gain of preterm newborns].

PMID- 15951917
TI  - [Quality of life in children with asthma].

PMID- 15951918
TI  - Predictive value of nailfold capillaroscopy in patients with Raynaud's
      phenomenon.
AB  - The objective of this study was to evaluate the long-term follow-up of patients
      with Raynaud's phenomenon (RP) and pathological nailfold capillaroscopy (NC) in
      order to analyse the predictive value of specific features of capillaroscopy for
      the development of a connective tissue disease (CTD). From 1992 to 2002, NC alone
      or combined with fluorescence videomicroscopy with sodium fluorescein (NaF) was
      performed in 1024 consecutive patients because of RP. We analysed the follow-up
      and pathological features of NC in all patients who had neither clinical nor
      serological signs of a CTD at the time of NC. Of 308 patients with neither
      serological findings nor clinical signs of CTD but with RP and pathological
      features in NC suspicious for CTD, follow-up data were available for 133
      patients. An additional NaF test had been performed in 51 (38.4%) patients. After
      a mean follow-up of 6.5 years (range: 1-15 years), 109 patients had developed a
      CTD and 24 patients did not show any clinical signs or serological markers for a
      CTD after a mean follow-up of 8.5 years (range: 2-15 years). There were no
      differences in age, duration of RP or of follow-up in patients who developed a
      CTD compared to patients who did not. Significantly more giant capillaries
      (p=0.0001), avascular fields (p=0.02) and irregular architecture (p=0.0001) had
      been observed in patients who had developed a CTD during the follow-up of 6.5
      years. The presence of giant capillaries, avascular fields and irregular
      architecture of nailfold capillaries is predictive for the development of a CTD
      in patients with RP.

PMID- 15951919
TI  - Is sildenafil effective in secondary pulmonary hypertension due to systemic lupus
      erythematosus? A case report.

PMID- 15951920
TI  - Influence of surgery-related factors on quality of life after esophageal or
      cardia cancer resection.
AB  - Knowledge of how factors related to esophageal cancer resection affect long-term
      quality of life after surgery is scarce, and no population-based studies are
      available. Therefore, we conducted a Swedish nationwide, prospective, population
      based study of how esophageal surgery-related factors influence quality of life 6
      months postoperatively. The Swedish Esophageal and Cardia Cancer register (SECC
      register) encompasses 174 hospital departments (97%). Microscopically radically
      operated patients responded to a validated written questionnaire assessing
      quality of life. The basic questionnaire (QLQ-C30) and the esophagus-specific
      module (OES-24) were developed by the European Organization for Research and
      Treatment of Cancer. The Mann-Whitney test, the Jonckheere-Terpstras test, and
      logistic regression were used in statistical analyses. Among 100 included
      patients, the occurrence of surgery-related complications was the main predictor
      of reduced global quality of life 6 months after surgery (p for trend = 0.03).
      This effect remained after adjustment for potential confounding variables. Except
      for anastomotic strictures, each of the predefined complications--i.e.,
      anastomotic leakage, infections, cardiopulmonary complications, and operative
      technical complications--contributed to decreased quality-of-life scores. Other
      potentially relevant factors--e.g. degree of lymph node dissection, resection
      margins, operative blood loss or duration, and hospital type--did not
      significantly affect quality of life. In conclusion, any measures that can reduce
      the risk of major surgery-related complications can decrease the negative impact
      on quality of life after esophageal cancer surgery. More population-based studies
      are warranted, however.

PMID- 15951922
TI  - Dopamine-secreting pheochromocytomas: in search of a syndrome.
AB  - Pheochromocytomas rarely produce dopamine as the only catecholamine. Two cases
      are reported here, and a review of the literature was conducted. Unlike
      norepinephrine-and epinephrine-secreting tumors, dopamine-secreting
      pheochromocytomas lack a classic clinical presentation and are often
      asymptomatic. Urinary and serum metabolites cannot be relied on to make the
      diagnosis, and serum or urine dopamine levels (or both) must be measured when
      dealing with a potential pheochromocytoma. Dopamine-secreting tumors are less
      likely to enhance with metaiodobenzylguanidine (MIBG) scanning and may benefit
      from the use of positron emission tomography. Treatment is en bloc surgical
      excision; but unlike other pheochromocytomas, alpha-blockade is not indicated as
      it may lead to hypotension and cardiovascular collapse. Metyrosine is a
      medication that can be useful for preoperative control of symptoms from these
      tumors. The function of metyrosine is to block dopamine synthesis; it has no
      alpha-blocking effect. This medication is an option for controlling symptoms but
      should not be used routinely in these patients. The prognosis for patients with
      these tumors is worse than for those with an epinephrine- and norepinephrine
      secreting tumor. Because of their asymptomatic nature, dopamine-secreting
      pheochromocytomas tend to be detected later and are more likely to be malignant
      at the time of diagnosis.

PMID- 15951921
TI  - Arterial reconstruction during pancreatoduodenectomy in patients with celiac axis
      stenosis--utility of Doppler ultrasonography.
AB  - Celiac axis stenosis is found at an incidence of 2%-24% in the general
      population. During pancreatoduodenectomy in patients with celiac axis stenosis,
      division of the gastroduodenal artery from the common hepatic artery may cause
      acute ischemia of the upper abdominal organs, such as the liver, stomach, or
      spleen. Under these circumstances, the clinical indications of arterial
      reconstruction remain controversial. Between 1994 and 2003, seven patients with
      celiac axis stenosis (n = 4) or occlusion (n = 3) underwent pancreatoduodenectomy
      at our hospital. Arterial reconstruction, including division of the median
      arcuate ligament, was conducted in two patients; the replaced right hepatic
      artery was preserved in one patient, and no vascular refinement was undertaken in
      the remaining four of the seven patients. In two of the four patients without
      arterial reconstruction or preservation, the serum levels of liver enzymes were
      markedly elevated (> 800 IU/l) on postoperative day 1, and these patients
      subsequently developed liver abscesses. Two patients who underwent arterial
      reconstruction and three patients who showed no decrease in intrahepatic arterial
      flow under Doppler ultrasonography after clamping of the gastroduodenal artery
      developed no ischemic complications. Although our experience is limited, when
      intraoperative Doppler ultrasonography indicates a decrease in the hepatic
      arterial signals, we believe that reconstruction of the hepatic artery will be
      necessary to minimize ischemic complications in the liver in patients with celiac
      axis stenosis.

PMID- 15951923
TI  - Emergency major abdominal surgery in patients over 85 years of age.
AB  - The aim of this retrospective study was to evaluate the outcome and prognostic
      parameters of patients over 85 years of age undergoing major abdominal emergency
      surgery. The medical records of 45 consecutive patients aged over 85 years who
      underwent major abdominal emergency surgery between May 1999 and November 2001
      were reviewed. The mean patient age was 88 years. Eight patients were American
      Society of Anesthesiologists (ASA) IV or V, 21 were ASA III, and 16 were ASA I or
      II. We performed 38 median and 7 right subcostal laparotomies. Perioperative
      mortality was 26.6% (3 times higher than that of the overall population at the
      same age). Perioperative complications occured in 29.5% of patients. Ten patients
      returned home after surgery, of whom 70% remained alive at the end of the study.
      Twenty-three left the hospital for a long-term care institution or post-acute
      care unit: of these 20% remained alive at the end of the study. Among ASA I or II
      patients, 43.7% remained alive at the end of the study, although 18.7% died
      within 1 month of the surgery. Among ASA III, IV, or V patients, only 17.2%
      remained alive at the end of the study, and 34.5% died within 1 month of the
      surgery. None of patients classified as ASA IV or V survived for more than 6
      month after surgery. With an overall mortality rate of about 30%, and with the
      clear correlation between increased mortality and higher ASA scores, the place of
      palliative treatment must remain a major consideration for patients in this age
      group classified ASA III or higher. When surgery is performed, early return home,
      should be encouraged.

PMID- 15951924
TI  - Elective inguinal hernia repair with mesh: is there a need for antibiotic
      prophylaxis?--A review.
AB  - Although it is widely accepted that antibiotic prophylaxis is indicated in
      elective mesh repair of inguinal hernia, the evidence for its value has been
      controversial. A recent Cochrane meta-analysis showed that there is insufficient
      data overall to demonstrate a clear advantage of prophylaxis and illustrated the
      classic problem in evidence-based medicine where a lack of evidence in support of
      an intervention may be interpreted as a reason not to implement it. This review
      of the literature evaluates the evidence for the effectiveness of intravenous
      antibiotics as prophylaxis in inguinal hernia repair with mesh. Pubmed and Embase
      searches revealed seven trials of antibiotic prophylaxis in mesh repair of
      inguinal hernia. The quality of the evidence and the limitations of the seven
      trials are discussed. Analysis of these seven trials adds to the Cochrane meta
      analysis of Sanchez-Manuel and Seco-Gil. Only two of the trials support the use
      of antibiotic prophylaxis, and those were the only double-blind randomized
      controlled trials reviewed. In evidence-based medicine the absence of evidence in
      clear support of an intervention (as in this review, where only two of the seven
      trials support the use of antibiotic prophylaxis) may be taken as reason not to
      implement the intervention. It is possible, however, that what is needed to
      clarify the issue are further randomized controlled trials, rigorously performed
      and recruiting significantly larger numbers of patients.

PMID- 15951925
TI  - Perforated peptic ulcer treated by simple closure and Helicobacter pylori
      eradication.
AB  - Simple closure followed by Helicobacter pylori (Hp) eradication has become the
      most used procedure in perforated ulcer treatment. However, its efficacy and
      safety are still to be determined. To assess recurrence and re-perforation rates,
      and as a secondary objective, to analyze Hp infection rates in perforated ulcer
      patients and controls, we conducted a prospective study. Ninety-two consecutive
      patients (ages: 19-96 years) were operated on between 1996 and 2002, and treated
      by simple closure followed by Hp eradication and NSAID avoidance. The data were
      prospectively collected in a database. Hp infection was diagnosed in 68 patients
      (73.9%). Thirty-four patients (37%) consumed nonsteroidal anti-inflammatory drugs
      (NSAIDs), and 23 (25%) had both Hp infection and NSAID antecedents. The
      perforation was gastric in 4 cases and pre-pyloric, pyloric or duodenal in 88.
      There were postoperative complications in 24 patients (26%) and 4 patients died
      (4.3%). Hp eradication was shown in 46 patients. There was clinical ulcer
      recurrence in 4 (4.3%); in 3 of them recurrence manifested as re-perforation, all
      in gastric locations. Overall relapse and re-perforation 1-year crude rates were
      6.1% and 4.1%, respectively. Crude rates for non-gastric ulcer recurrence were 0
      at 1 year and 2.6% at 2 years and for non-gastric ulcer re-perforation rates were
      0 at 1 and 2 years. This therapeutic strategy is associated with a low rate of
      recurrence and no re-perforations in case of duodenal, pyloric, or pre-pyloric
      perforated ulcers, but it is not acceptable for perforated gastric ulcers.

PMID- 15951926
TI  - Intra-abdominal and retroperitoneal lymphangiomas in pediatric and adult
      patients.
AB  - Intra-abdominal and retroperitoneal lymphangiomas are a rare, congenital
      malformations of the lymphatics, which are found predominantly in children. The
      aim of this study is to evaluate the clinical features of this tumor,
      highlighting the differences in adults and pediatric patients. We also evaluate
      the preoperative diagnosis, radiological features, surgical treatment, and
      outcome of this rare condition. Between 1990 and 2004, 14 patients who underwent
      surgical resection of an intra-abdominal lymphangioma were reviewed
      retrospectively. There were five pediatric patients between fetal age and 17
      years of age and nine adults between 31 and 62 years of age. Overall, females
      outnumbered males in the series, with a male-to-female ratio of 3:4. However,
      males predominated in the pediatric age group with a male-to-female ratio of
      1.5:1. The clinical presentation of children was more acute ranging from 3 days
      to 2 months. In adults, four patients were asymptomatic, and the remaining five
      had symptom duration ranging from 2 weeks to a year. The lymphangiomas occurred
      in the mesentery (n = 4), retroperitoneum (n = 4), omentum (n = 3), pancreas (n =
      2), and spleen (n = 1). All the patients underwent total surgical resection with
      or without organ resection, and there were no recurrences at a median follow-up
      of 2 years (range; 3 months--13 years). This series demonstrates that abdominal
      lymphangiomas have a male preponderance and present more acutely in pediatric
      patients, whereas in adults, female patients predominate and the history is more
      chronic.

PMID- 15951927
TI  - Ultrasonographically and anatomopathologically detectable node metastases in the
      lateral compartment as indicators of worse relapse-free survival in patients with
      papillary thyroid carcinoma.
AB  - The recent prevalence of ultrasonography has made it easier to detect lymph node
      metastasis in the lateral compartment of patients with thyroid carcinoma. In this
      study, we investigated the prognostic impact of lateral node metastasis
      preoperatively detectable by ultrasonography (US) and metastasis diagnosed by
      pathology examination but not detected on preoperative US [anatomopathologically
      (AP)-detectable metastasis] in 560 patients with papillary carcinoma >1 cm in
      diameter, who underwent thyroidectomy with modified radical neck dissection at
      our hospital. Patients with US-detectable metastasis (US+ patients) showed a
      significantly worse relapse-free survival (RFS) rate than those with no
      metastasis (US-/AP- patients) or AP-detectable metastasis (US-/AP+ patients)
      regardless of tumor size. Furthermore, the RFS of US-/AP+ patients with tumors >2
      cm was worse than that of US-/AP- patients with tumors >2 cm or US-/AP+ patients
      with tumors measuring 1.1-2.0 cm. There was no significant difference in RFS
      between US-/AP+ and US-/AP- patients with tumors measuring 1.1-2.0 cm. These
      findings suggest that US-detectable lateral metastasis predicts a worse RFS for
      patients regardless of tumor size, and AP-detectable metastasis affects the RFS
      of patients with tumors >2 cm.

PMID- 15951928
TI  - Practical usefulness of ultrasonic surgical aspirator with argon beam coagulation
      for hepatic parenchymal transection.
AB  - The objective of this study was to evaluate the effectiveness and feasibility of
      using the Cavitron ultrasonic surgical aspirator (CUSA) with argon beam
      coagulation (ABC) during hepatic resection, in comparison with a conventional
      method using CUSA with bipolar cautery. Between April 2003 and March 2004, a
      series of 14 consecutive patients underwent hepatic resection of normal liver.
      Hepatectomies were performed using CUSA and bipolar irrigation electrocautery
      (BP) in eight patients between April 2003 and December 2003. CUSA and an ABC were
      used in six patients between January 2004 and March 2004. There were no
      differences in patient characteristics between the two groups. Blood loss per
      area of transected liver surface was significantly lower for CUSA with ABC than
      for CUSA with BP (2.9 +/- 1.44 vs. 6.33 +/- 3.14 ml/cm2). Furthermore, the speed
      of resection, defined as resection time per area of transected liver surface, was
      significantly greater for CUSA with ABC than for CUSA with BP (0.53 +/- 0.14 vs.
      2.18 +/- 1.73 min/cm2). This new technique of combining CUSA with ABC can
      decrease blood loss during hepatic parenchymal transection and shorten the
      resection time.

PMID- 15951929
TI  - Primary closure of the common duct over endonasobiliary drainage tubes.
AB  - The T-tube remains the standard method of intraductal drainage after open
      choledochotomy for choledocholithiasis. We studied the use of an endonasobiliary
      drainage (ENBD) tube as an alternative to the T-tube for postoperative
      intraductal drainage. A series of 20 patients with documented choledocholithiasis
      in whom endoscopic methods of stone retrieval failed to clear the common bile
      duct (CBD) were selected for the study. All patients had ENBD tubes placed
      preoperatively at endoscopic retrograde cholangiopancreaticography and then were
      subjected to open choledocholithotomy with primary closure of the choledochotomy
      over the ENBD. The age of the patients in the study group ranged from 18 to 75
      years. Three patients (15%) had acute cholangitis at the time of surgery. Stones
      were confirmed at surgery in 85% of the patients, and the size of the CBD was
      found to range from 1.0 to 2.3 cm. All 20 patients underwent closure of the
      common duct over an ENBD tube without any difficulty. None of the patients
      experienced biliary complications such as bile leaks, biliary peritonitis,
      biliary fistula, pancreatitis, or cholangitis. No patient had any residual stone
      as documented by postoperative cholangiograms. Abdominal drains remained in place
      for 2 to 4 days, and the ENBD tubes were removed between days 6 and 8. The length
      of the postoperative hospital stay varied from 7 to 15 days, with 65% of the
      patients going home before postoperative day 8.

PMID- 15951930
TI  - Comparison of surgical techniques for treatment of benign toxic multinodular
      goiter.
AB  - Controversy remains regarding the best surgical approach for toxic multinodular
      goiter (MNG). The aim of this study was to evaluate the results of various
      thyroid operations for managing toxic MNG. A group of 100 patients with toxic MNG
      were divided into three groups and managed with total thyroidectomy (TT; group I,
      n-17), near-total thyroidectomy (NTT; group II, n = 48), or bilateral subtotal
      thyroidectomy (BST; group III, n = 35). Patients were compared with regard to
      age, gender, surgical operations, complications, thyroid hormone status, duration
      of hospitalization, and the reoperation rate for incidentally found thyroid
      carcinomas. There were 14 men (14%) and 86 women (86%) with a mean age of 47.03
      +/- 13.56 years (range 19-77 years). After the operation two patients had a
      hematoma, and one patient had a seroma. Four patients had unilateral vocal cord
      paralysis, and one had permanent paralysis. Moreover, 18 patients had transient
      and 2 patients permanent hypocalcemia. There was no significant difference
      between the groups regarding complications (p < 0.05). Permanent hypothyroidism
      was achieved in all patients in group I and 44 patients (92%) in group II,
      whereas in group III only 10 (29%) patients had hypothyroidism. Conversely,
      hyperthyroidism, both subclinical and clinical, was noted only in group III (12
      patients, 34%) during follow-up. We think that TT and NTT are safe, effective
      approaches in the treatment of toxic MNG, preventing recurrence of thyrotoxicosis
      and reoperation for incidentally found thyroid cancers. The complication rates
      for TT and NTT were similar to that for BST. Hence these operation should be
      considered for patients referred for surgical treatment of toxic MNG.

PMID- 15951931
TI  - Clinicopathological factors predicting long-term overall survival after
      hepatectomy for peripheral cholangiocarcinoma.
AB  - Peripheral cholangiocarcinoma (PCC) is clinically challenging because patients
      typically do not present until the disease is relatively advanced. Three-year to
      5-year survival rates even with resection thus remain dismal. This study aimed to
      determine the clinicopathological factors for predicting overall survival longer
      than 5 years in PCC patients treated with hepatectomy. From 1977 to 1997, the
      clinicopatholgical features of 11 PCC patients who underwent hepatectomy with
      long-term overall survival (group A) were reviewed. Comparison was made with the
      clinical features and factors influencing the outcome of 70 PCC patients who
      survived less than 5 years after hepatectomy (group B). Of 81 PCC patients
      undergoing hepatectomy, 11 (13.6%) were 5-year survivors. The 81 PCC patients
      comprised 32 men and 49 women, with a mean age of 56.0 years (range: 34-83
      years). Univariate analysis showed that female gender, absence of physical
      findings, a higher percentage of presence of mucobilia, early staged tumor,
      intraductal papillary tumor growth, and curative hepatic resection were more
      frequent in group A patients than group B patients. However, multivariate
      logistic regression analysis showed that absence of physical findings, presence
      of mucobilia, early staged tumor, and curative hepatic resection were the four
      independent factors differentiating group A from B patients. The 1-, 3-, 5-, and
      10-year survival rates of the group A patients were 100%, 100%, 100%, and 40%,
      whereas those of the group B patients were 46.0%, 9.5%, 0%, and 0%, respectively.
      Absence of physical findings, presence of mucobilia, early staged tumor, and
      curative hepatectomy could independently predict PCC patients with long-term
      overall survival after hepatectomy.

PMID- 15951932
TI  - Patient-controlled dietary schedule improves clinical outcome after gastrectomy
      for gastric cancer.
AB  - Although studies have shown that early oral feeding after abdominal surgery is
      feasible, the optimal dietary schedule has not been established. This study was
      conducted prospectively to compare the clinical outcome of patient-controlled
      dietary schedule with that of conventional dietary schedule after gastric
      resection for early cancer. Patients in the patient-controlled diet (PC) group (n
      = 53) received a solid diet on demand; patients in the conventional regimen (CR)
      group (n = 50) received a solid diet from postoperative day (POD) 10. All
      patients underwent distal gastrectomy for early gastric cancer. A liquid diet was
      tolerated by the PC group on POD 2, and a solid diet was taken on POD 6 after
      gastrectomy, earlier than in the CR group. The postoperative hospital stay was
      18.5 +/- 5.9 days (10-40) in the PC group, versus 21.7 +/- 8.8 days (14-57) in
      the CR group (p = 0.02). Patients in the PC group had a higher daily oral intake
      of calories on POD 10 than those in the CR group (p = 0.02). Changes in body
      weight and serum albumin during the postoperative period and after discharge, and
      the incidence of complications and variances from clinical pathways did not show
      significant differences between the two groups. The PC schedule was feasible
      after distal gastrectomy for early gastric cancer. It improved the clinical
      outcome, with a shorter postoperative hospital stay and a higher oral energy
      intake on early phase, compared with the CR schedule. Moreover, the PC approach
      was useful for establishing the optimal dietary schedule and improving the
      clinical pathway.

PMID- 15951933
TI  - Non-Oriental primary intrahepatic lithiasis: experience with 48 cases.
AB  - An experience with the diagnosis and treatment of patients with non-Oriental
      primary intrahepatic lithiasis (PIHL) is described. A group of 48 native
      Brazilian patients with symptomatic PIHL were studied, and the patients'
      characteristics, diagnoses, treatment protocols based on the presentation of the
      disease, prognostic factors, and late results were analyzed. Liver resection was
      performed in patients with an irreversible lesion, such as parenchymal atrophy or
      biliary stenosis; and biliary drainage procedures were employed in patients with
      bilateral disease. Late results were considered good when no postoperative
      symptoms were observed and poor if there was pain recurrence or cholangitis.
      Overall good results were observed in 73.4% of the patients. Good late results
      were observed in 94.1% and 62.1% of the patients with unilateral and bilateral
      stones, respectively. None of the analyzed parameters (gender, age, previous
      biliary surgery, bilirubin level, serum leukocyte counts, prothrombin activity,
      previous history of cholangitis, stone location) predicted poor late results, but
      the risk for patients with bilateral stones to develop late complications was 7.2
      times higher than for those with unilateral disease. Non-Oriental PIHL is a rare
      disease, and the patients' characteristics are similar to those of patients with
      Oriental PIHL. We believe that personalized treatment based on the presentation
      of the disease led to the high incidence of good late results in this series.

PMID- 15951934
TI  - Tumor necrosis factor-alpha, interleukin-1beta and nitric oxide: induction of
      liver megamitochondria in prehepatic portal hypertensive rats.
AB  - It has been shown that portal hypertension in the rat causes microvesicular
      hepatocytic fatty infiltration. Formation of megamitochondria (MG) is one of the
      most prominent alterations in steatosis. Because nitric oxide (NO), tumor
      necrosis factor-alpha (TNFalpha), and interleukin-1beta (IL-1beta) impair
      mitochondrial function, these mediators have been studied in prehepatic portal
      hypertensive rats to verify their coexistence with MG and therefore with
      steatosis. Male Wistar rats were divided into two groups: a control group (n = 7)
      and a group with partial portal vein hgation (n = 19) at 6 weeks of evolution.
      TNFalpha and IL-1beta were quantified in liver by enzyme-linked immunosorbent
      assay, and NO was measured in the portal vein, suprahepatic inferior vena cava,
      and infrahepatic inferior vena cava by the Griess reaction. In portal
      hypertensive rats, the serum concentration of NO of hepatic origin increases
      (132.10 +/- 34.72 vs. 52.44 +/- 11.32 nmol/ml; p < 0.001), as do TNFalpha (2.02
      +/- 0.20 vs. 1.12 +/- 0.43 micromol/mg protein) and IL-1beta (18.95 +/- 2.59 vs.
      5.48 +/- 1.70 micromol/mg protein) (p = 0.005) in the liver. The most frequent
      hepatic histologic findings are the presence of MG (p < 0.001), steatosis, and
      hyperplasia. An increase in hepatic release of NO, TNFalpha and IL-1beta with MG
      formation is produced in rats with portal hypertension. Therefore these
      proinflammatory mediators and this morphologic mitochondrial alteration could
      both be involved in the etiopathogenesis of steatosis.

PMID- 15951935
TI  - Prediction of metastasis to non-sentinel nodes by sentinel node status and
      primary tumor characteristics in primary breast cancer in Taiwan.
AB  - We aimed to determine how to approach the axilla after finding a positive
      sentinel node (SN) for a woman with breast cancer in Taiwan. We used blue dye
      staining to identify the SN in 824 procedures on 811 patients with breast cancer
      small than 3 cm by a single surgeon. All patients underwent SN biopsy, followed
      by at least level II axillary dissection. All SNs were evaluated histologically
      and immunohistochemically with anti-cytokeratin antibodies. Non-SNs were examined
      by routine histology. SNs were identified in 814/824 procedures (98.8%). SN
      metastases were found in 286/814 (35.1%). Subsequent axillary dissections
      revealed tumors in non-SNs in 188 (65.7%) of these patients. There was a
      relatively high incidence of non-SN metastases in our population. Tumor
      exhibiting high nuclear grading, ER-, PR-, Erb-2/neu overexpression,
      lymphovascular invasion, increasing tumor size, multiple positive SNs, and
      macrometastatic size in SNs (> 2 mm) were all significantly correlated with non
      SN metastases. Multivariate analysis showed that tumor size, the number of
      positive SNs, and the metastatic size in SNs were independent factors predicting
      the presence of positive non-SNs. Small (< 2 cm) cancers, having only
      micrometastatic foci in the SN and having only one SN involved are closely
      correlated with the tumor-free non-SNs. Our data will assist such patients
      regarding the need for axillary dissection after finding a positive SN.

PMID- 15951936
TI  - Myocardial perfusion defects and the left ventricular ejection fraction disclosed
      by scintigraphy in patients with primary hyperparathyroidism.
AB  - Patients with primary hyperparathyroidism (PHPT) have increased risk of
      cardiovascular disease. For patients undergoing preoperative parathyroid imaging
      with 99mTc-sestamibi single photon emission computed tomography (SPECT), we
      combined cervical SPECT and gated cardiac SPECT to achieve information about the
      localization of parathyroid adenomas, myocardial perfusion, and the left
      ventricular ejection fraction (LVEF) at rest. A series of 22 patients with PHPT
      and no history of myocardial infarction or angina pectoris were recruited
      consecutively. At 60 minutes after injection of 700 MBq 99mTc-sestamibi, SPECT of
      the neck and gated myocardial perfusion SPECT were performed at the same time.
      All of the patients who underwent parathyroidectomy had the parathyroid adenoma
      localized as predicted from the SPECT. Five patients (23%) had myocardial
      perfusion defects extending more than 15% (range 15-25%), and they had higher
      plasma parathyroid hormone levels (p = 0.03), and lower LVEF (p = 0.007) than
      patients without perfusion defects. We suggest that patients with
      hyperparathyroidism and suspected cardiovascular disease can undergo 99mTc
      sestamibi parathyroid SPECT simultaneously with gated myocardial perfusion SPECT
      to obtain information about the resting perfusion status and cardiac systolic
      function. The results from myocardial perfusion SPECT can lead to initiation of
      cardiovascular treatment and eventually perioperative precautions.

PMID- 15951937
TI  - General anesthesia for surgery influences melatonin and cortisol levels.
AB  - The purpose of this study was to investigate the effect of general anesthesia and
      surgery on melatonin production, and to assess the relationship between melatonin
      secretion and cortisol levels. Twenty (9 males and 11 females) consecutive
      otherwise healthy patients aged 27 to 52 years were included in this study. The
      patients underwent laparoscopic cholecystectomy or laparoscopic hernioplasty. All
      patients had general anesthesia with the same anesthetic drugs. Serum cortisol
      levels were measured at several time periods. Urine collections for melatonin
      were performed from 18:00 to 7:00 the day prior to surgery, on the operation day,
      and on the first postoperative day. Baseline melatonin metabolites were measured
      the night prior to surgery, and the level was found to be 1979 +/- 1.76 ng. The
      value decreased to 1802 +/- 1.82 ng (NS) on the night of surgery, and it became a
      significantly higher, reaching 2981 +/- 1.55 ng the night after surgery (p =
      .003). The baseline daytime cortisol level was significantly lower than the
      baseline night cortisol level (6.87 +/- 1.51 microg/dl, 14.89 +/- 1.66
      micrograms/dl, respectively, p < 0.0001). Surgery induced a significant increase
      in both day and night cortisol levels. Daytime cortisol levels increased from
      6.89 +/- 1.51 microg/dl to 16.90 +/- 1.27microg/dl (p < 0.0001), whereas right
      levels increased from 14.89 +/- 1.66 microg/dl to 29.20 +/- 1.24 microg/ dl (p
      <0.0001). The morning after surgery, cortisol levels decreased to 10.16 +/- 1.40
      microg/dl, lower than the value obtained on the day of surgery (p < 0.0001). As
      was true of melatonin, cortisol levels did not reach the pre operative level (p <
      0.005). The finding of the current study is that melatonin and cortisol levels
      show an inverse correlation after surgery.

PMID- 15951938
TI  - Is the size of an abdominal aortic aneurysm associated with coagulopathy?
AB  - Abdominal aortic aneurysm (AAA) volume and intraluminal thrombi were analyzed
      with respect to the number and function of platelets, blood cells, and
      coagulation factors. A group of 43 patients who underwent repair of an AAA were
      enrolled in this study. The maximum diameter and volume of the AAA, and the
      volume of intraluminal thrombi and lumen were measured by computed tomography
      with planimetry. The platelet count and platelet function, prothrombin time,
      activated partial thromboplastin time, fibrinogen, plasminogen, antithrombin 3,
      fibrin degradation products (FDP), D-dimer, and blood cell counts were measured.
      Spontaneous platelet aggregation and the FDP, and D-dimer levels were elevated;
      all other factors remained within the normal range. Intraluminal thrombus volume
      was strongly correlated with the volume and diameter of the AAA. However, no
      correlation was observed between the size of the AAA and coagulating factors,
      including the number and aggregation value of platelets. AAAs are frequently
      associated with a coagulating disorder. However, its size and thrombus volume are
      not correlated with coagulation changes. Although an intraluminal thrombus
      increases along with fee enlargement of the AAA, the clinical manifestation of
      bleeding is rarely associated with an AAA. Therefore coagulopathy in patients
      with an AAA is not fully explained by its morphology.

PMID- 15951939
TI  - Prospective randomized study of T-tube versus biliary stent for common bile duct
      decompression after open choledocotomy.
AB  - The T-tube has been the alternative of choice for decompression following common
      bile duct (CBD) exploration. The development of laparoscopic surgery has
      suggested using a biliary stent as an alternative to the T-tube following
      choledochotomy. The purpose of this prospective randomized study was to compare
      clinical results obtained from patients who underwent open CBD exploration using
      a biliary stent versus those from patients with a T-tube for decompression.
      Between September 2000 and June 2002 a total of 81 patients were randomly
      assigned to a biliary stent or a T-tube as the decompression method following
      choledochotomy. An open CBD exploration was performed when CBD stones were
      suspected, in both elective and emergency settings. The length of the
      postoperative hospital stay was 6.8 +/- 4.7 days for patients with the T-tube and
      of 5.2 +/- 3.3 days for, patients with the biliary stent (p = 0.19).
      Postoperative complications were observed in 13 patients (30%) with the T-tube
      and in 4 patients (11%) with the biliary stent (p = 0.03). One patient with a
      biliary stent was reoperated because of an intraabdominal abscess, and another
      patient was reoperated because of biliary peritonitis following T-tube removal.
      Three patients (7%) with a biliary stent and one patient (3%) with a T-tube were
      rehospitalized. There were no deaths. The T-tube and biliary stent were removed
      27.1 +/- 10.8 days and 34.9 +/- 12.9 days after surgery, respectively (p = 0.24).
      The biliary stent is a safe alternative to the T-tube as a biliary decompression
      method following an open CBD exploration.

PMID- 15951940
TI  - Complications with reconstruction procedures in pylorus-preserving
      pancreaticoduodenectomy.
AB  - This study was conducted retrospectively to examine the efficacy of Traverso
      reconstruction compared with Billroth I reconstruction after pylorus-preserving
      pancreaticoduodenectomy, in the prevention of several complications. Pylorus
      preserving pancreaticoduodenectomy is an aggressive surgery, and insufficiency of
      the pancreaticoenterostomy plays an important role in the postoperative
      progression. However, reports examining the correlation between pancreatic
      fistula and the type of reconstruction after pylorus-preserving
      pancreaticoduodenectomy have been limited. Sixty-four patients who underwent
      pylorus-preserving pancreaticoduodenectomy (33 reconstructed by the Traverso
      technique and 31 reconstructed by the Billroth I technique) were entered into
      this study to investigate whether the complications were related to the type of
      reconstruction procedure employed. Insufficiency of the pancreaticojejunostomy,
      including major leakage and pancreatic fistula, occurred in 18.2% of the
      reconstructions by Billroth I and 0% of the reconstructions by Traverso (p <
      0.05). In addition, jejunal obstruction by recurrent tumor in the remnant
      pancreas was observed in 3 patients reconstructed by Billroth I, and required
      palliative bypass surgery. Reconstruction by the Traverso procedure after pylorus
      preserving pancreaticoduodenectomy is a safe surgical method and has an advantage
      for advanced pancreatic cancer, which has high risk of jejunal obstruction by
      recurrent tumor in the remnant pancreas.

PMID- 15951941
TI  - Giant liver hemangioma: therapy by enucleation or liver resection.
AB  - Hemangioma is the most common primary tumor of the liver. The widespread use of
      ultrasonography (USG) and computed tomography (CT) has made the diagnosis more
      common. Although the vast majority of hemangiomas are diagnosed incidentally and
      are asymptomatic, treatment is still controversial. Surgery is the treatment of
      choice, especially in giant, symptomatic hemangiomas and uncertainty of
      diagnosis. Twenty-two patients (median age: 46 years) underwent resection (n =
      12) or enucleation (n = 10) for liver hemangioma from 1989 to 2002. The primary
      indication for surgery was abdominal pain. Ten patients who were treated by
      enucleation were compared with twelve patients who were treated by liver
      resection. Mean tumor size was 90 mm with a range of 40-270 mm. There were no
      statistically significant differences in tumor size, preoperative liver function
      tests, hemoglobin levels, and platelet counts between the two groups. Operative
      time was longer in the resection group, and statistically significant the
      difference was (p = 0.048). Blood transfusion requirement and blood loss during
      intraoperative period were higher in the resection group (p = 0.025, p = 0.01,
      respectively). There were three postoperative complications, 1 in the enucleation
      group (pleural effusion), 2 in the resection group (liver abscess and wound
      infection). There was no surgery-related mortality in either group. Although most
      hemangiomas can be removed by enucleation or liver resection with low morbidity
      and mortality, if the location and number of hemangiomas are appropriate,
      enucleation is the choice of the therapy. Hospital stay, blood transfusion
      requirement, and blood loss can be kept minimal by the selection of enucleation.

PMID- 15951943
TI  - Ischemic preconditioning versus intermittent vascular inflow control during major
      liver resection in pigs.
AB  - Ischemic preconditioning (IPC) and intermittent vascular control (IVC) have been
      shown to reduce the number of ischemia/reperfusion injuries during liver
      resections with the Pringle maneuver. Our study aimed to compare the beneficial
      effect of these two modalities in relation to the duration of normothermic liver
      ischemia. A group of 24 Landrace pigs with a mean body weight of 25 to 30 kg were
      subjected to extended liver resection of more than 65%. Although, 12 animals
      underwent IPC (10 minutes of ischemia and 10 minutes of reperfusion), and
      subsequently the Pringle maneuver was applied for 90 minutes (n= 6) or 120
      minutes (n= 6). Another 12 animals underwent liver resection by IVC (20 minutes
      of ischemia alternated with 5 minutes of reperfusion) for 60 minutes (n = 6) or
      120 minutes (n = 6) of inflow vascular control. At 90 minutes of liver ischemia,
      the IPC group demonstrated lower levels of asportate aminotransferase (AST) (173
      +/- 53 vs. 265 +/- 106 IU; p =0.089) and malondialdehyde (MDA) (2.60 +/- 1.03 vs.
      5.33 +/- 2.25 micromol/L; p =0.022) and higher liver tissue cAMP (200 +/- 42 vs.
      146 +/- 40 pmol/g wet wt, p = 0.04) compared to the IVC group. However, no
      pathologic differences were observed between the two groups. By contrast, at 120
      minutes of liver ischemia, IVC proved to be more beneficial, reflected by lower
      levels of AST (448 +/- 135 vs. 857 +/- 268 IU; p = 0.006) and MDA (8.33 +/- 1.75
      vs. 12.7 +/- 4.31 micromol/L; (p = 0.045), a higher cAMP level (127 +/- 10 vs. 97
      +/- 31 pmol/g wet wt p = 0.045), and eventually less cellular necrosis (necrosis
      score 1.66 +/- 0.51 vs. 2.85 +/- 1.16; p = 0.04) compared to the IPC group. It
      appears that IPC should be employed when liver ischemia is anticipated to last
      less than 90 minutes, followed by IVC when the liver ischemia is expected to last
      120 minutes.

PMID- 15951944
TI  - Reconsideration of delayed gastric emptying in pancreaticoduodenectomy.
AB  - Literature reports indicate that the incidence of delayed gastric emptying (DGE)
      is higher after pylorus-preserving pancreaticoduodenectomy (PPPD) than after
      conventional pancreaticoduodenectomy (CPD), but DGE is traditionally diagnosed
      from patient-reported subjective sensations. Our clinical radiological experience
      suggests higher rates for physiological DGE post-CPD. We therefore sought to
      quantify rates of subjective DGE (sDGE, based on patient complaint) verses
      objective DGE (oDGE, based on scintography) post-CPD and post-PPPD. Contractile
      motility of post-PPPD residual stomach was also studied. For 21 PPPD and 33 CPD
      patients between October 1997 and June 2000, sDGE and oDGE data were collected
      preoperatively, on postoperative day 14, and 6 months postoperatively, with
      cholescintography for pylorus ring competency on postoperative day 14. The
      incidence of sDGE was higher for PPPD (42%) than for CPD (15%) at 14 days, with
      zero sDGE for both at 6 months. The incidence oDGE was higher for CPD (91%) than
      for PPPD (76%) at 14 days, with a 6-month incidence of 4.7% in PPPD but
      approximately 33% for CPD. Solid-phase emptying in PPPD showed that residual
      stomach retained partial gastric emptying function at 14 days but not at 6
      months. Cholescintography showed abnormal pylorus closure function in 2 of 21
      PPPD patients but was not related to DGE. Literature reports of higher DGE
      incidence post-PPPD are true only for subjective symptoms. Radiological
      measurement of oDGE shows that both CPD and PPPD manifest approximately 80%
      incidence of DGE in the early postoperative period. At 6 months, approximately
      33% of CPD show persistent oDGE. We concluded that (1) the concept of DGE should
      distinguish between subjective and objective symptoms; (2) loss of distal stomach
      mechanoreceptors in CPD reduces patients sensation of oDGE, producing "silent"
      DGE; (3) both CPD and PPPD have high and approximately equal rates oDGE; (4) the
      previously unnoticed silent oDGE in CPD may contribute to the higher rates of
      ulceration and related morbidity in association with CPD.

PMID- 15951945
TI  - Discovery.

PMID- 15951951
TI  - Randomized controlled trial.

PMID- 15951952
TI  - Beneficial effects of glutamine on intestinal barrier function in obstructive
      jaundice.

PMID- 15951955
TI  - Ratio of male to female births in the offspring of BRCA1 and BRCA2 carriers.
AB  - A recent report based on 68 families, including 17 with mutations in BRCA1,
      suggested that there was an excess of female offspring born to BRCA1 mutation
      carriers. We have examined the gender ratio among offspring of 511 mutation
      carriers from 116 BRCA1 families, 77 and 39 from Australia and the United States,
      respectively. We found no evidence for a significant deviation from the expected
      proportion of female offspring in the Australian pedigrees, but there was an
      excess of female offspring in pedigrees from the USA. Ascertainment bias probably
      explains this bias, rather than a link with X-chromosome inactivation as
      previously suggested, because the families from the USA were ascertained for the
      purposes of linkage studies whereas those from Australia were ascertained through
      Familial Cancer Clinics to which they had been referred for clinical genetic
      counseling and mutation testing.

PMID- 15951956
TI  - High prevalence of two BRCA1 mutations, 4154delA and 5382insC, in Latvia.
AB  - Our aim was to characterise the germline BRCA1 mutation profile in Latvian breast
      cancer and ovarian cancer patients, to develop an effective BRCA1 gene mutation
      detection strategy, and to document genotype-phenotype correlations in mutation
      carriers. The entire BRCA1 gene was analysed in 75 breast cancer and 30 ovarian
      cancer patients. Screening for three mutations (5382insC, 4154delA and 300T>G)
      was carried out in 55 breast cancer and 66 ovarian cancer patients, and for two
      mutations, 5382insC and 4154delA, in 376 unselected patients with any cancer
      (including 51 breast cancer and 29 ovarian cancers) and 215 women with any
      gynaecological tumour. Mutation detection techniques used were SSCP/HD analysis
      or F-SSCP (ABI PRISM 310). Five different deleterious mutations were detected by
      analysis of the entire BRCA1 gene. The proportion of cases with mutations amongst
      50 breast cancer patients diagnosed before 48 years was 26.0% (95% CI: 14.6
      40.3%). Two mutations (5382insC and 4154delA) made up more than 80% of all
      mutations identified by the analysis of the entire BRCA1 gene in Latvia, at
      present. Further screening for only the prevalent mutations in different cancer
      patient groups resulted in the identification of 53 more mutation carriers. We
      conclude that breast cancer diagnosed before the age of 48 years and ovarian
      cancer before 65 years are criteria for DNA testing to be offered to women in
      Latvia, regardless of cancer history in the family. The observed associations of
      specific prevalent mutations with cancer site and age at onset of disease are
      discussed.

PMID- 15951957
TI  - The Tyr978X BRCA1 mutation: occurrence in non-Jewish Iranians and haplotype in
      French-Canadian and non-Ashkenazi Jews.
AB  - BACKGROUND: The Tyr978X BRCA1 mutation is a founder mutation detected in high
      risk Iraqi-Iranian Jewish families as well as in the general non-Ashkenazi
      population. The same mutation was also reported in non-Jewish high-risk women
      from Canada. Its occurrence in non-Jewish individuals from Iran has never been
      tested. OBJECTIVE: Assess the occurrence rate of Tyr978X BRCA1 germline mutation
      in the general population of Iranian non- Jewish individuals and compare the
      BRCA1-linked haplotype of Jewish and non-Jewish mutation carriers. METHODS: PCR
      amplification of the relevant fragment of the BRCA1 gene, followed by restriction
      enzyme digestion that differentiates wild type from mutant allele. For
      haplotyping, 7 BRCA1-linked markers were used. The tested population included 442
      apparently healthy Iranian non-Jewish individuals, and 17 mutation carriers from
      Israel and Canada. RESULTS: The Tyr978X BRCA1 mutation was not detected in any
      Iranian non-Jewish individual. The intragenic haplotype of all Jewish Israeli
      mutation carriers was identical, but differed from that of Canadian non-Jews in
      two intragenic markers. CONCLUSIONS: The Tyr978X BRCA1 mutation which is a
      founder mutation in Jews, may be a hot spot in non-Jewish high risk women, and
      probably does not represent a rare sequence variant in Iranian non-Jews.

PMID- 15951959
TI  - The use of preventive measures among healthy women who carry a BRCA1 or BRCA2
      mutation.
AB  - PURPOSE: The purpose of this study was to assess women's knowledge about
      tamoxifen, to examine the frequency of tamoxifen usage and other preventive
      measures in BRCA1/2 mutation carriers, and to document women's concerns about
      taking tamoxifen for chemoprevention. METHODS: One hundred and twenty five women
      with known BRCA1 or BRCA2 mutation and with no prior diagnosis of breast or
      ovarian cancer were identified through the records of two large cancer genetics
      clinics. These women had been counseled about their cancer risk and various
      preventive options were discussed. At a time from two to 110 months following
      disclosure session, a questionnaire was sent by mail. Women were asked about
      their current and past use of tamoxifen, their knowledge of risks and benefits,
      their desire for additional information, and their experience with other
      preventive measures. RESULTS: Eighty-one of 125 eligible women returned the
      questionnaire (64.8%). Ten women (12.3%) had used tamoxifen and eight women had
      used raloxifene (9.9%). Twenty-two women (27.2%) had undergone prophylactic
      mastectomy and 54 women (66.7%) had had an oophorectomy. Twelve women (14.8%) did
      not recall discussing tamoxifen. Thirty-five women (58.3%) said that their
      doctors had not provided them with sufficient information about tamoxifen to
      consider its use. Fear of side-effects was the most common reason for not taking
      tamoxifen. CONCLUSION: Although tamoxifen appears to be effective in preventing
      breast cancer in women with a BRCA1 or BRCA2 mutation, few women now take the
      drug compared to those who choose other preventive measures including surgery.
      Health care providers should provide accurate information about the risks and
      benefits of tamoxifen to allow women to make informed decisions.

PMID- 15951958
TI  - A high frequency of germline BRCA1/2 mutations in western Sweden detected with
      complementary screening techniques.
AB  - Dominant inheritance is presumed in 6-10% of breast and ovarian cancers.
      Mutations in BRCA1 and BRCA2 genes are the most commonly identified causative
      genes in such families. The frequency of mutation carriers with breast/ovarian
      cancer depends on the population studied, and display considerable variation that
      coincides with ethnic and geographical diversity. Mutation analyses were
      performed in 143 families registered at the Cancer Genetic Counseling Clinic of
      western Sweden. In a thorough mutation screening procedure, the entire BRCA1 and
      BRCA2 genes were analyzed using a combination of complementary mutation detection
      techniques. Mutations in either BRCA1 or BRCA2 were detected in 36% (52 out of
      143) of all screened families. All families were clinically evaluated regarding
      age at diagnosis, type of cancer and number of cancer cases in the family. Among
      high-risk families, the mutation detection rate was 39% (46 out of 117). The
      detection rate observed among families with cases of ovarian cancer (42 out of
      62, 68%), was substantially higher than in families with only breast cancer (10
      out of 81, 12%). Age at ovarian cancer did not seem to have an effect on the
      detection rate. The analyses revealed 11 frameshift mutations, 4 nonsense
      mutations and 2 large deletions. Notably, the BRCA1 c.3171ins5 mutation accounted
      for 34 of 52 (65%) identified mutations. Seven mutations are novel:
      BRCA1c.409_410del; c.1912T>G; c.2228_2229del; c.3029delA; c.3433delA, a large
      deletion covering exons 1-3 of BRCA1and one BRCA2 mutation; BRCA2c.6287_6290del.
      We have shown that the founder mutation BRCA1 c.3171ins5 has a great influence on
      western Swedish breast/ovarian cancer families along with a high number of
      mutations unique for the region. In order to achieve a high mutation detection
      rate we suggest a combination of several detection techniques.

PMID- 15951960
TI  - Predictors of participation in clinical and psychosocial follow-up of the kConFab
      breast cancer family cohort.
AB  - INTRODUCTION: Prospective collection of epidemiological, psychosocial and outcome
      data in large breast cancer family cohorts should provide less biased data than
      retrospective studies regarding penetrance of breast cancer and modifiers of
      genetic risk. METHODS: The Kathleen Cuningham Foundation for Research into Breast
      Cancer (kConFab) recently commenced 3-yearly follow-up on over 750 families with
      multiple cases of breast cancer. Clinical follow-up was by mailed self-report
      questionnaire to all participants, while psychosocial follow-up was only of
      unaffected women and consisted of two components: a mailed questionnaire and an
      interview regarding stressful life events. RESULTS: To date, 1928 of 2748 (70%)
      participants returned the clinical follow-up questionnaire (10% opted out, 16%
      were non-responders, and 4% were not contactable). Of the unaffected females who
      returned the clinical follow-up questionnaire, 91% participated in the
      psychosocial follow-up. In multivariate analyses, sex, personal cancer status,
      marital status, age and educational status were independent predictors of
      response to the clinical follow-up questionnaire, and number of female children,
      age, and family history of breast cancer were independent predictors of response
      to the psychosocial follow-up. CONCLUSIONS: A first round of 3-yearly clinical
      and psychosocial follow-up using a mailed questionnaire was feasible in this
      cohort. High response rates were achieved by employing intensive tracing and
      reminder strategies. The predictors of response for the clinical and psychosocial
      follow-up components of this study should be considered in designing similar
      follow-up strategies for other family cancer cohorts.

PMID- 15951961
TI  - Genetic uptake in BRCA-mutation families is related to emotional and behavioral
      communication characteristics of index patients.
AB  - INTRODUCTION: Carriers of a hereditary mutation in BRCA are at high risk for
      breast and ovarian cancer. The first person from a family known to carry the
      mutation, the index person, has to share genetic information with relatives. This
      study is aimed at determining the number of relatives tested for a BRCA mutation,
      and the exploration of facilitating and debilitating factors in the transmission
      of genetic information from index patient to relatives. METHODS: The study
      includes 50 female index patients, with a germline mutation in either BRCA1 or
      BRCA2. RESULTS: The percentage of first- and second-degree relatives tested for
      the BRCA-mutation was 36%. Uptake levels for predictive BRCA-mutation testing
      could not be explained by demographic or counseling characteristics, nor by
      cancer-related history. In 14 families, fewer than 20% of first- and second
      degree relatives were tested. These families were compared with the other
      families. In retrospect, the index patients of families with few BRCA-mutation
      tests more often asked for support in the communication with family members (62%
      vs. 27%). A psychosocial worker had been absent more often during counseling (39%
      vs. 9%). Emotional factors debilitating the information transmission were only
      reported by index patients from families with few BRCA-mutation tests (18% vs.
      0%), who also informed their parents less often (21% vs. 67%) and did so less
      often personally (38% vs. 71%). CONCLUSION: Uptake of predictive BRCA-mutation
      testing by first- and second-degree relatives is low. Emotional and behavioral
      factors of index patients are related to this uptake.

PMID- 15951962
TI  - Psychological distress in women at risk of hereditary breast/ovarian or HNPCC
      cancers in the absence of demonstrated mutations.
AB  - AIM: To examine psychological distress in women at risk of familial breast
      ovarian cancer (FBOC) or hereditary non-polyposis colorectal cancer (HNPCC) with
      absence of demonstrated mutations in the family (unknown mutation). MATERIALS AND
      METHODS: Two-hundred and fifty three consecutive women at risk of FBOC and 77 at
      risk of HNPCC and with no present or past history of cancer. They were aware of
      their risk and had received genetic counseling. Comparisons were made between
      these two groups, normal controls, and women who were identified to be BRCA1
      mutation carriers. The questionnaires Beck Hopelessness Scale (BHS), General
      Health Questionnaire (GHQ-28), Hospital Anxiety and Depression Scale (HADS) and
      Impact of Event Scale (IES) were employed to assess psychological distress.
      RESULTS: No significant differences concerning psychological distress were
      observed between women with FBOC and women with HNPCC. Compared to mutation
      carriers for BRCA1, the level of anxiety and depression was significantly higher
      in the FBOC group with absence of demonstrated mutation. Compared to normal
      controls, the level of anxiety was higher, while the level of depression was
      lower in the groups with unknown mutation. CONCLUSIONS: Women in the absence of
      demonstrated mutations have higher anxiety and depression levels than women with
      known mutation-carrier status. Access to genetic testing may be of
      psychologically benefit to women at risk for FBOC or HNPCC.

PMID- 15951963
TI  - A comparison of the phenotype and genotype in adenomatous polyposis patients with
      and without a family history.
AB  - OBJECTIVES: Adenomatous polyposis of the colon is often secondary to an inherited
      mutation in adenomatous polyposis coli (APC) gene, however, approximately one
      third of patients have no family history of the disease. We studied the phenotype
      and genotype of adenomatous polyposis in patients without a family history.
      METHODS: A cohort of 57 unrelated adenomatous polyposis patients were evaluated.
      Seventeen patients with no family history were compared with 40 patients who had
      a positive family history of the disease. Family history and medical records were
      collected and analyzed. Germline APC and Mut Y homologue (MYH) testing was
      undertaken. RESULTS: Patients without a family history were diagnosed with
      polyposis at an older age (41 years vs. 32 years) and presenting more frequently
      with symptoms (76 vs 20, P < 0.05). The number of colonic polyps and frequency of
      extracolonic manifestation associated with adenomatous polyposis did not differ
      between the two groups. APC mutations were detected less frequently among
      patients without a family history of the disease (4 out of 17 vs 25 out of 40,
      P=0.007), even among those with greater than 100 colorectal adenomas (4 out of 12
      versus 21 out of 29, P=0.03). One homozygous MYH mutation carrier (G382D) was
      detected among the six patients without a family history and without a germline
      APC mutation who were tested. CONCLUSIONS: Adenomatous polyposis patients without
      a family history are usually diagnosed with symptoms, and at a later age.
      Phenotypically, they are similar to those with a family history. However,
      germline APC mutations are detected far less frequently in patients without a
      family history. A small percentage of these cases may be secondary to biallelic
      germline MYH mutations.

PMID- 15951964
TI  - Abdominal desmoid in familial adenomatous polyposis presenting as a pancreatic
      cystic lesion.
AB  - A 17-year-old male with familial adenomatous polyposis (FAP) presented with chest
      pain and significant weight loss. An abdominal CT scan detected a cystic
      pancreatic lesion of unknown etiology. The patient therefore underwent surgical
      resection of the distal pancreas, which included the lesion, because of the known
      association of pancreatic cancer with FAP. Histopathological examination of the
      resected specimen showed a benign pancreatic cyst and fibrous plaque with desmoid
      fibromatosis adherent to the surface of the pancreas, serosa of the stomach, and
      colon. The fibrous plaque was histologically identical to the fibrous mesenteric
      plaque known to occur in FAP and associated mesenteric fibromatosis. We present
      pathologic evidence that the pancreatic cyst formation was induced by FAP
      associated desmoid invasion. Desmoid growth should be considered in the
      differential diagnosis of a pancreatic cystic mass lesion in patients with FAP or
      its Gardner syndrome variant. This case report provides the first pathologic
      evidence for benign epithelial cyst formation in the pancreas caused by
      fibromatosis invasion of that organ as a part of FAP.

PMID- 15951965
TI  - An unusual case of Turcot's syndrome associated with ileal adenocarcinoma,
      intestinal non-Hodgkin's lymphoma, and duodenal adenocarcinoma. Review of the
      classification and genetic basis of Turcot's syndrome.
AB  - A 38-year-old man with a history of colonic and small bowel polyposis and
      glioblastoma was investigated for dyspepsia. Upper GI endoscopy identified an
      abnormal area in the duodenum, confirmed by histology as high grade non-Hodgkin's
      B cell MALT lymphoma. Although cases of Turcot's syndrome (TS) (colonic polyposis
      and primary brain tumour occurring in the same patient) have been previously
      described, association with haematological malignancy is rare. This is the first
      report of intestinal lymphoma occurring in an adult with TS.

PMID- 15951966
TI  - Screening for exonic copy number mutations at MSH2 and MLH1 by MAPH.
AB  - BACKGROUND: Exonic deletions in MSH2 and MLH1 are significant contributors to the
      mutation spectrum in HNPCC, and heterozygous changes in exon copy number are not
      detected by conventional mutation screening methods. AIMS: We aimed to develop
      methods for screening copy number changes in all the exons of the MLH1 and MSH2
      genes using a single multiplex amplifiable probe hybridisation (MAPH) assay.
      METHODS: We developed a probe set consisting of probes from the 19 exons of MLH1
      and 16 exons of MSH2, and 3 control probes, and applied it to screening for
      deletions and duplications using fluorescent detection of amplified fragments.
      RESULTS: We tested 73 DNA samples from controls and 50 from HNPCC patients in
      whom no point mutations had been found, and detected 10 copy number changes among
      the patient samples. A deletion of about 1.4 kb including exon 3 of MSH2 was
      confirmed by amplification of a junction fragment, and was shown to be the result
      of an unequal recombination between intronic Alu elements. CONCLUSIONS: MAPH can
      detect exonic copy number changes in MLH1 and MSH2 in DNA from HNPCC patients.
      Since finding an exonic deletion or duplication makes full sequence analysis
      unnecessary, it may be most cost-effective to pre-screen samples by MAPH or MLPA
      before screening for point mutations.

PMID- 15951967
TI  - Referrals of patients to colorectal cancer genetics services in south-east
      Scotland.
AB  - The discovery that genetic factors are involved in the aetiology of colorectal
      cancer, has prompted many relatives of affected individuals to seek genetic
      counselling and screening. This paper describes the demand for genetic services
      by families with colorectal cancer in south-east Scotland, their expectations and
      views of the service offered. The annual referral rate over the 21-month study
      period, for patients with a family history of colorectal cancer, was 0.11 per
      1000 patients on general practitioner lists. This is one third of the rate for
      patients with a family history of breast cancer and in comparison with the breast
      cancer group, relatives of colorectal cancer patients were significantly older
      and less socially deprived. Approximately one third were referred via a hospital
      specialist unit. One hundred patients were included in the study. Mean (+/-
      standard deviation) age was 43 (+/- 10.7 years), 75 were female and 31 were self
      referrals. Before the consultation, almost half the patients had an inflated
      perception of their risk and there was little change at follow-up. There was an
      improvement in objective understanding after counselling which was sustained up
      to 6 months but only two thirds remembered their objective risk accurately. Most
      patients were satisfied with the consultation. Our findings suggest the need to
      educate individuals, in particular men, younger people and the more socially
      deprived, about the relevance of a family history of colorectal cancer and to
      facilitate patients' comprehension of their risk status.

PMID- 15951968
TI  - Informing one's family about genetic testing for hereditary non-polyposis
      colorectal cancer (HNPCC): a retrospective exploratory study.
AB  - BACKGROUND: The family-link approach of case finding is considered the fastest
      and most efficient approach to trace people with hereditary disease. Therefore,
      there is a need to understand if, why, and how people with hereditary non
      polyposis colorectal cancer (HNPCC) inform their biological family. AIM: To
      explore people's perspective on informing one's biological family regarding a
      hereditary predisposition for HNPCC. METHOD: In-depth interviews were conducted
      with 30 people recruited from the database of the Netherlands Foundation for
      Detection of Hereditary Tumours (STOET). Interviews were transcribed and analyzed
      thematically. FINDINGS: Disclosure was stimulated if people felt morally obliged
      to do so or when they anticipated regret if something happened because it is
      preventable. Motivation to disclose seemed to increase if there were, especially
      fatal, cancer cases in the family. Presence of external cues (e.g. professionals)
      appeared important for disclosure as well. Disrupted and tense family relations
      were reasons not to disclose, as well as young age of the message recipients and
      negative experiences at their first attempt to disclose (a novel finding).
      Disclosure was merely restricted to the nuclear family. A personal approach in
      this respect was preferred. With respect to content of the disclosure,
      participants reported to solely announce the presence of the hereditary defect
      and the possibility of testing. It was mostly considered the recipients'
      responsibility and own choice to obtain further (technical/medical) information.

PMID- 15951969
TI  - SISE matters: the sum of information on seventy-yr-old equivalents measures
      pedigree information content when assessing the risk of HNPCC in a family.
AB  - Hereditary non-polyposis colon cancer (HNPCC) is a significant cause of
      colorectal and other malignancies. Due to the lack of features that reliably
      differentiate between a sporadic case and an inherited case of colon cancer, it
      is likely that HNPCC is under reported. The diagnosis of HNPCC relies heavily on
      finding multiple cases of colorectal or other specific cancers within a family.
      In the absence of a significant family history, a diagnosis of HNPCC is seldom
      considered. We postulate that small kinships--or, more specifically, kinships
      with a low information content--are more likely to be designated as having a low
      risk of an inherited cancer predisposition than are large kinships. This has the
      potential to exacerbate the under-diagnosis of HNPCC in small families, leading
      to inadequate treatment, follow-up and family counselling. We have developed an
      objective measure of the information content of individual pedigrees called the
      Sum of Information on Seventy-yr-old Equivalents (SISE) coefficient. The SISE
      coefficient is a function of the number of relatives in a kinship and their
      relationship to the proband, of their ages and of the age-dependent penetrance of
      HNPCC mutations. A population-based series of colorectal cancer cases was
      assessed, by currently accepted methods, for the likelihood of there being an
      HNPCC mutation segregating in each family. We observed that families with a low
      SISE coefficient were significantly more likely to be designated at low risk of
      HNPCC (P< or =0.001). Using a cumulative binomial distribution function, we
      estimated the likelihood of observing multiple cancers in families of different
      SISE coefficients.

PMID- 15951970
TI  - The TP53 mutational spectrum and frequency of CHEK2*1100delC in Li-Fraumeni-like
      kindreds.
AB  - Li-Fraumeni syndrome (LFS) is a dominantly inherited cancer predisposition
      syndrome characterized by a wide spectrum of neoplasms occurring at young age.
      Germline mutations in the TP53 tumor suppressor gene have been identified in
      approximately 71 of LFS patients and 22 of Li-Fraumeni-like (LFL) patients.
      Mutations within the cell cycle checkpoint gene CHEK2 have also been reported in
      some patients with LFS, LFL, and phenotypically suggestive of LFS (PS-LFS) not
      carrying a TP53 mutation. In this study, we show that 7 of the 23 patients with
      LFS/LFL tested positive for deleterious mutations in p53. Fifteen of the
      remaining sixteen were not found to carry the CHEK2* 1100delCmutation. These
      results indicate that CHEK2*1100delC is not a common cause of LFS, LFL, or PS-LFS
      in North American kindreds not carrying a TP53 mutation. Of note, two patients
      were found to carry p53* R72P, which is of unknown clinical significance. Lack of
      segregation of this allele in one of these kindreds provides strong evidence that
      the R72P allele is not disease-causing. While mutations in p53 account for a
      proportion of patients with LFS/LFL, future studies are needed to determine if
      other genes are responsible for LFS/LFL families not carrying germline p53
      mutations.

PMID- 15951971
TI  - The CHEK2 1100delC allele is not relevant for risk assessment in HNPCC and HBCC
      Spanish families.
AB  - The frame-shift mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene
      (CHEK2) has been reported to be a low penetrance breast cancer gene in Northern
      European populations. However, the variant may be relevant for breast cancer risk
      in other populations, due to its low prevalence. Recent studies have proposed a
      role for the mutation in colorectal cancer, finding a strong association between
      the CHEK21100delC mutation and hereditary breast and colorectal cancer (HBCC). A
      previous study suggested that the CHEK21100delC variant was not of clinical
      relevance in Spanish breast/ovarian cancer families. Here, we demonstrate that
      this genetic variant is not of clinical relevance for HNPCC and HBCC Spanish
      families.

PMID- 15951972
TI  - APC and beta-catenin protein expression patterns in HNPCC-related endometrial and
      colorectal cancers.
AB  - OBJECTIVE: The adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) genes
      are the two major components of the Wnt signaling pathway that has been shown to
      play an important role in the formation of certain cancers. The overactivation of
      the pathway, which results in abnormal accumulation of beta-catenin protein in
      nuclei, contributes to most colorectal cancers (CRCs), both sporadic and
      hereditary, as well as sporadic endometrial cancers (ECs). Here, we studied the
      involvement of APC and beta-catenin in hereditary nonpolyposis colorectal cancer
      (HNPCC)-related ECs, and compared the expression patterns to those in HNPCC
      related CRCs. MATERIALS AND METHODS: Nineteen ECs and 31 CRCs derived from HNPCC
      patients were immunohistochemically stained with anti-APC- and anti-beta-catenin
      antibodies. RESULTS: Tumor-specific loss of APC was observed in 16 of endometrial
      cancers (3 of 19) and in 39 of colorectal cancers (12 of 31). Consistently, the
      loss of APC expression was associated with nuclear beta-catenin staining.
      Altogether, aberrant beta-catenin localization was observed in 53 of ECs (10 of
      19) as compared to 84 of CRCs (26 of 31) (P=0.02). CONCLUSION: Our results
      suggest a frequent overactivation of the Wnt signaling pathway in hereditary
      endometrial cancer. In accordance with studies on sporadic cancers, abnormal
      accumulation of beta-catenin protein in nuclei occurred much less frequently in
      HNPCC-related ECs than CRCs, which may reflect organ-specific differences in
      their pathogenesis.

PMID- 15951973
TI  - The BRCA1 exon 13 duplication in the Swedish population.

PMID- 15951974
TI  - Measurement of psychological factors associated with genetic testing for
      hereditary breast, ovarian and colon cancers.
AB  - Despite numerous individual studies of psychological factors (depression,
      anxiety, distress) related to genetic testing for inherited cancer syndromes
      (CGT), there has been no systematic review of the psychological factors are
      measured among individuals at increased risk for hereditary breast, ovarian, or
      colon cancer. Our review provides an analysis of psychological factors in studies
      of CGT and discusses the instruments most commonly used to measure them. We
      performed a literature search using three major OVID databases from 1993 to
      January 2003. In the 19 studies that met our inclusion criteria, the most
      commonly assessed psychological factors were distress, anxiety, and depression.
      These factors were most often measured by the impact of event scale (IES), the
      state-trait anxiety inventory (STAI), and the Centers for Epidemiologic Studies
      and Depression scale (CES-D), respectively. Our results show deficits in the
      existing body of literature on psychological factors associated with CGT
      including limited documentation of psychometrics and variability in
      instrumentation.

PMID- 15951975
TI  - History of artificial organs in Japan.

PMID- 15951976
TI  - Mechanical circulatory support devices (MCSD) in Japan: current status and future
      directions.
AB  - The current status and future directions of mechanical circulatory support
      devices (MCSDs) in Japan are reviewed. Currently used clinical MCSDs, both
      domestic and imported systems and continuous flow devices that are coming into
      the clinical arena are emphasized. Clinical MCSDs include the extracorporeal
      pulsatile Toyobo and Zeon systems and the implantable Novacor and HeartMate I VE.
      A thorough review is presented of single-ventricle continuous flow MCSDs such as
      the Terumo DuraHeart and the SunMedical EVAHEART and the biventricular
      Miwatec/Baylor systems that are on the horizon. The future directions in
      management of end-stage cardiac patients with MCSDs are discussed, focusing on
      (1) device selection - pulsatile versus continuous flow devices; (2) single
      ventricle support, biventricular support, or replacement; (3) bridge to
      transplantation, destination therapy, or bridge to recovery; and (4) government
      regulatory processes and the medical industry. We hope to promote the quality of
      life (QOL) of end-stage cardiac patients as well as the medical industry in
      Japan.

PMID- 15951977
TI  - Postoperative hyperbilirubinemia after implantation of left ventricular assist
      device is associated with poor postoperative liver perfusion.
AB  - Hyperbilirubinemia, a common complication associated with left ventricular assist
      device (LVAD) implantation, is evidence of liver dysfunction and is often a life
      threatening problem after the implantation procedure. In this study we evaluated
      the relationship between hemodynamics after LVAD implantation and postoperative
      hyperbilirubinemia. Twenty-four patients who received LVADs at Osaka University
      Hospital between January 1994 and June 2002 were retrospectively reviewed.
      Patients were grouped according to the implanted LVAD: Group A (n = 4) Novacor,
      group B (n = 7) HeartMate 1000IP, group C (n = 13) Toyobo pneumatic pulsatile
      pump. Hemodynamic data and laboratory data, including total bilirubin on
      postoperative days (PODs) 1, 3, 7, and 14, were collected and statistically
      analyzed. In group C, the cardiac index (CI) on POD 1 was significantly lower (P
      < 0.01) than that for groups A and B. On PODs 3 and 7, total bilirubin levels in
      group C increased significantly over the preoperative value (P < 0.05) and were
      significantly higher than those in group A on POD 3 and higher than those in
      groups A and B on POD 7 (P < 0.05). Regression analysis of CI on POD 1 correlated
      significantly with total bilirubin on POD 7, as expressed by the formula y =
      5.13/(x - 1.7)(0.719), where x is CI and y is total bilirubin (r(2) = 0.327, P <
      0.05). Total bilirubin after LVAD implantation correlates with postoperative CI
      values. We suggest that it is essential to maintain the CI at the highest levels
      possible to avoid postoperative hyperbilirubinemia in LVAD patients.

PMID- 15951978
TI  - Japanese multicenter clinical evaluation of the HeartMate vented electric left
      ventricular assist system.
AB  - Implantable left ventricular assist device systems (LVAS) are increasingly being
      used to bridge patients to heart transplantation because of the limited number of
      available donor hearts. This prospective, multicenter trial was designed to
      evaluate the usefulness of the HeartMate vented electric (VE) LVAS as a bridge to
      transplantation in Japan. Between November 2001 and June 2003, six patients with
      end-stage heart failure [New York Heart Association (NYHA) class IV] were
      supported with the LVAS and five of the six were able to implement the evaluation
      (one dropped out). The five were men with an average age of 38.6 years and were
      supported for 2390 cumulative days (6.6 years). Average preimplant cardiac index
      improved from 1.93 l/min/m(2) to a 3.79 l/min/m(2) VAD flow index at the end of
      the clinical trial. All five patients improved to NYHA class I or II, survived
      more than 1 year, and one patient was discharged from the hospital. Mean LVAS
      support duration was 478 days (range 390-575 days) and four patients remain
      supported. One patient died from cardiac failure and sepsis. Device-related
      complications included: infections (four patients), thromboembolism (one
      patient), hemolysis (two patients), and repeat operation for bleeding (two
      patients). There was one case of inflow valve incompetence and two pump motor
      malfunctions. We conclude that the LVAS can effectively support patients as they
      await cardiac transplantation and offers improvement to the patient's quality of
      life.

PMID- 15951979
TI  - Changes in platelet aggregation during cardiopulmonary bypass: comparison of poly
      2-methoxyethylacrylate and heparin as a circuit coating material.
AB  - At present, there are various biomaterials that have high biocompatibility. In
      particular, there are many types of coated circuits in cardiopulmonary bypass
      (CPB) systems. However, only a few clinical studies have investigated platelet
      aggregation caused by these coated circuits. In this study, a CPB system coated
      with poly-2-methoxyethylacrylate (X coating) was used to ascertain whether
      platelet aggregation could be suppressed during CPB, and a comparison was made
      between X coating and ordinary (covalently bonded) heparin coating. The subjects
      were 19 adult patients who were scheduled to undergo valve replacement or
      valvuloplasty. They were divided into two groups: group X (X coating) and group H
      (heparin coating). The platelet aggregation threshold index (PATI, grading curve)
      and beta-thromboglobulin and plalelet factor IV levels were assessed
      preoperatively (control), 5 min after heparin administration, 10 and 60 min after
      the start of CPB, and 0 and 2 h after the end of CPB. The results indicated that
      platelet aggregation was reduced during CPB and that platelets were activated.
      The changes in platelet aggregation associated with the X coating were shown to
      be similar to those associated with heparin coating.

PMID- 15951980
TI  - Effects of muscle potential depression and muscle stimulation caused by different
      insulation coating configurations on cardiac pacemakers.
AB  - Insulation coating was added to the external pacemaker surface to prevent
      unnecessary electric current leakage to the periphery because the pulse generator
      body is used as an anode in unipolar pacing. However, a model without insulation
      coating has recently been used, so we studied the effects on muscle potential
      inhibition and muscle stimulation of pacemakers in unipolar pacing with different
      parts of the pacemaker body coated with insulation. Case comparisons were made
      for the following models: insulated except for the center of one side (33, group
      C), insulated except for the peripheral zone (10, group E), and noncoated models
      (11, group N). The muscle detection threshold voltage, muscle detection threshold
      pulse duration, muscle potential sensing threshold (MP), and lead resistance were
      measured. A comparison was made of the amount of energy (En) needed to reach the
      muscle stimulation threshold. For MP values, there was no significant statistical
      difference between group C and E, whereas a significant difference was present
      between group C and N and between group E and N. For En values, there was a
      significant difference between group C and E and between group C and N, but there
      was no significant difference between group E and N. The muscle potential sensing
      threshold dose not have a change in group E and much muscle stimulation energy is
      needed. The muscle potential sensing threshold was low in group N, requiring much
      muscle stimulation energy. Based on these results, it is usually not necessary to
      coat the pacemaker with insulation for unipolar pacing.

PMID- 15951981
TI  - The CarboMedics prosthetic heart valve: experience with 180 implants.
AB  - At Jichi Medical School Hospital, three types of mechanical prosthetic valves
      (CarboMedics, Omnicarbon, Bicarbon) were used without randomization from 1991 to
      2000. A retrospective study of valve replacements done between June 1991 and
      November 2000 utilizing 180 CarboMedics valves in 145 patients who had not
      previously undergone prosthetic valve replacement or aortic root and/or arch
      replacement was conducted to evaluate midterm patient outcomes to assess the
      future continuous use of CarboMedics valves. Women made up 47.6% of the patients
      and the mean age was 57.5 years (range 12-80 years). Preoperative New York Heart
      Association functional class was III or IV in 92.4% (134/145) of patients. Mean
      follow-up of 4.5 years (range 0-10.0 years) was 95.9% complete, with a total of
      628 patient-years (PY). Early (within 30 postoperative days) mortality was 5.5%
      (8 of 145): 3 from hemorrhage, 3 from nonvalve-related heart failure, 1 from
      infection, and 1 from arrhythmia. There were 16 late deaths (2.54%/PY): 1 from
      hemorrhage, 4 from unknown causes/sudden death, 4 from nonvalve-related heart
      failure, and 7 from other noncardiac causes. A total of 121 patients (83.0%) were
      alive at the last follow-up, done in November 2000. The linearized death rate was
      3.82%/year (including 1.11%/year for valve-related deaths). Linearized death
      rates from various causes were: bleeding, 0.96%/year; thromboembolism,
      1.11%/year; thrombosis, 0.39%/year; perivalvular leak, 0.96%/year; endocarditis,
      0%/year; hemolysis, 0%/year; and reoperation, 0.63%/year. No structural valve
      failure was observed. Comparative early mortality rates of valve replacement
      without aortic root replacement or arch replacement, excluding repeat valve
      replacement operations, in our institute, were 3.5% (12/307) for all valve types
      used contemporaneously, 2.6% (2/76) for Omnicarbon valves, and 2.3% (2/86) for
      Bicarbon valves. Although the CarboMedics valve had a rather high mortality rate
      of 5.5% (8/145) compared with the total early mortality rate of 3.5%, the low
      incidence of valve-related complications might support the continued use of the
      CarboMedics valve for valve replacement.

PMID- 15951982
TI  - Development and validation of models for the investigation of blood clotting in
      idealized stenoses and cerebral aneurysms.
AB  - An in vitro model of blood clotting is presented using hypercoaguable milk as an
      analog for blood. Milk clot formation was studied for periods of 2, 5, 10, 20,
      and 30 min within an idealized stenosis geometry. Clot formation was recorded
      using photography, clot casting, and clot mass calculation. The distribution of
      clot within the fluid was seen to be in good agreement with a previous study that
      used a residence time model to predict areas of clot formation in thrombin
      solution. A numerical model was formulated within computational fluid dynamics
      package CFX that allowed local activation of blood clotting to be simulated. This
      model was applied to the analysis of an idealized cerebral aneurysm geometry. An
      idealized coil geometry was included within the aneurysm and clotting fluid
      concentration and fluid residence time were modeled using transport equations
      within CFX. The viscosity of the fluid was defined as a function of both
      residence time and clotting fluid concentration. The model was seen to produce
      features consistent with observations of thrombosis within cerebral aneurysms,
      while avoiding the unrealistic build up of clot in near-wall regions that is
      associated with a pure residence time model.

PMID- 15951983
TI  - End-tidal carbon dioxide monitoring indicates recovery from cardiogenic shock in
      patients receiving percutaneous cardiopulmonary support.
AB  - The aim of this study was to examine the prognostic value of monitoring end-tidal
      carbon dioxide (ETCO(2)) levels for patients in cardiogenic shock undergoing
      percutaneous cardiopulmonary support (PCPS). Fifteen patients in whom PCPS was
      used to treat cardiogenic shock were enrolled in this study. For hemodynamic
      measurements, a thermodilution catheter was inserted into the pulmonary artery
      and an infrared absorption sensor was placed in the main stream of exhaled air
      between the respiration tube and the respirator to measure ETCO(2) levels. Nine
      patients (group II, 60%) died of multiple organ failure. In the six survivors
      (group I), there was a significant increase in average ETCO(2) level from 8.8 +/-
      3.9 mmHg before treatment to 20.5 +/- 2.1 mmHg 24 h after the start of PCPS
      compared with values in group II patients (8.8 +/- 3.9 mmHg, P = 0.0411). Also,
      serum lactate concentrations fell significantly in group I patients (group I 2.8
      +/- 0.47 mmol/l, group II 9.0 +/- 2.31 mmol/l, P = 0.0435). The mean ETCO(2)
      level in group I patients gradually returned to 23 mmHg, which was within the
      normal healthy range; these patients were successfully weaned from PCPS. These
      results suggest that, in cardiogenic shock patients, ETCO(2) level is a possible
      index of cardiac recovery during PCPS support.

PMID- 15951984
TI  - Long-term outcomes using vascular grafts sealed with fragmented autologous
      adipose tissue for aortoiliac occlusive disease.
AB  - The aim of this study was to test the safety and efficacy of fragmented
      autologous adipose tissue (FAT) grafts for revascularization in aortoiliac
      occlusive disease. Twenty-seven patients with atherosclerotic aortoiliac
      occlusive disease underwent surgical treatment using FAT grafts. A piece of
      adipose connective tissue was obtained from the operative wound, cut into small
      pieces, and pressed into the wall of a fabric vascular prosthesis. Cumulative
      primary patency rates were 92% at 1 year, 92% at 3 years, and 86% at 6 years.
      Cumulative secondary patency rates were 96%, 96%, and 90% for the same intervals.
      In this clinical study, the FAT grafts demonstrated good long-term patency rates
      and no particular problems. This is the first clinical report of long-term
      outcomes using FAT grafts for aortofemoral or aortoiliac bypasses. FAT grafts are
      thus safe for revascularization in aortoiliac occlusive disease.

PMID- 15951985
TI  - [Adiposis. A somatic or psychic disorder?].
AB  - Obesity, defined as a body mass index of > or =30 kg/m(2), is a modern epidemic
      and is increasing worldwide. Depending on genetic make-up, lifestyle factors such
      as nutrition, physical activity, and psychosocial conditions are the main
      determinants of its manifestation and severity. Numerous epidemiological studies
      show consistently that obesity is associated with many comorbidities and,
      moreover, reduces life expectancy. For this reason, there is a need for evidence
      based treatment considering the individual risk. For patients with extreme
      obesity exceeding a BMI of 40 kg/m(2), surgical intervention is the most
      effective treatment, not only to improve most somatic and psychological
      comorbidities significantly but also to prolong life.

PMID- 15951986
TI  - Prophylactic and interventional granulocyte transfusions in patients with
      haematological malignancies and life-threatening infections during neutropenia.
AB  - Patients with haematological malignancies and prolonged periods of neutropenia
      after chemotherapy are at high risk for severe bacterial and fungal infections.
      Those infections have long time been considered as a contraindication for
      subsequent haematopoietic stem cell transplantation (HCT). We conducted a
      prospective, non-randomized study of granulocyte transfusions (GTX) to control
      acute life-threatening infections (44 episodes) and to prevent recurrence of
      severe fungal infections during HCT or intensive chemotherapy (23 episodes). GTX
      achieved control in 82% (36/44) of acute life-threatening infections. No single
      reactivation of a previous infection occurred under prophylactic GTX (0/23).
      Median survival was 170 days in the interventional group and 185 days in the
      prophylactic group; death in both patient groups was mainly due to underlying
      progressive malignant disease. We conclude that under GTX, the infection-related
      mortality even in high-risk patients is low. Due to a secondary prophylaxis with
      GTX, haematopoietic allografts can be safely given to patients with previous
      fungal infections.

PMID- 15951987
TI  - Clinical spectrum and surgical approach of adult intussusceptions: a multicentric
      study.
AB  - BACKGROUND: The preoperative diagnosis of adult intussusceptions (AIs) remains
      difficult, and the assessment of the radiological methods has been evaluated very
      little in the literature. The aim of this study was to evaluate the interest of
      the different imaging modalities for the preoperative diagnosis of AI and
      describe causes of AI. PATIENTS AND METHODS: Consecutive patients of 15 years and
      older with the postoperative diagnosis of intussusception from 1979 to 2004 were
      reviewed retrospectively for this multicentric study. Data concerning clinical
      considerations, morphological examinations, surgical procedure, histological
      conclusions, mortality rate and recurrence were analysed. RESULTS: Forty-four
      patients with documented intussusception were included. The mean age was 51 years
      (15-93 years). The preoperative diagnosis of intussusception was made in 52% of
      the cases. The sensitivities of the different radiological methods were abdominal
      ultrasounds (35%), upper gastrointestinal barium study (33%), abdominal computed
      tomography (CT) (58%) and barium enema (73%). An organic lesion was identified in
      95% of the cases. There was 29 enteric and 15 colonic (including appendicular)
      intussusceptions. Thirty-seven percent of the enteric lesions were malignant, and
      a bit less than 50% of them were metastatic melanomas. The benign enteric lesions
      were Meckel's diverticulum and Peutz-Jeghers syndrome in half of the cases. Fifty
      eight percent of the pure colonic lesions (excluding appendix) were malignant,
      and 85% of them were primary adenocarcinomas. The benign colonic lesions were
      lipomas in 80% of the cases. All patients, except one, had a surgical treatment,
      and 13 of them had a complete reduction of the intussusception before resection.
      The mortality rate was 16% and recurrence occurred in three patients; two of them
      had a Peutz-Jeghers syndrome. CONCLUSION: Intussusception rarely occurs in
      adults, but nearly half of their causes are malignant. The CT scan is a helpful
      examination for enteric intussusceptions whether barium enema seems to be the
      most performing method for colonic lesions. Surgery is the recommended treatment,
      with or without a primary reduction of the intussusception. During the surgical
      procedure, this reduction can lead to a more limited bowel resection.

PMID- 15951988
TI  - Complications and reoperations in stapled anopexy: learning by doing.
AB  - Although stapled anopexy for second and third degree hemorrhoids has been widely
      used since 1998, there are limited long-term data available. We performed an
      analysis of a prospectively accrued data set of all patients undergoing stapled
      anopexy in our practice from 1998 through August 2003. Patients were specifically
      assessed for early and late complications and long-term reoperation rates for
      anorectal pathology. We performed stapled anopexy in 654 patients (296 females)
      during the study period. Mean operation time was 21 min (5-70 min), and the
      postoperative stay was 3.6 days (1-13 days). Early postoperative complications:
      urinary retention, 42 patients (6.4%); fecal impaction, 18 (2.8%); postoperative
      hemorrhage, 26 (4.0%); thrombosed external hemorrhoid, four (0.6%); and
      fistula/abscess, nine (1.4%). Late postoperative complications: anastomotic
      dehiscence, 21 patients (3.2%); persistence of prolapse in three (0.5%);
      submucosal anastomotic cysts in four (0.6%); thrombosed external hemorrhoid in
      two (0.3%); skin tags in ten (1.5%); fissure in six (0.9%); proctitis in two
      (0.3%); and fecal incontinence in ten (1.5%). Reoperation was required in 50
      patients (7.6%). Reoperation for complications within 30 days occurred in 42
      patients (6.4%) for the following reasons: bleeding (23), dehiscence (five),
      thrombosed external hemorrhoid (three), fecal retention (two), fistula (three),
      fissure (five), and anal papilla (one). Reoperation for anorectal pathology after
      30 days was required in 54 patients (8.3%) and was performed for the following:
      dehiscence/reprolapse (17), stenosis (two), submucous cyst (two), fistula (four),
      fissure (six), anal papilla (four), skin tags (five), persistent anal itching
      (five), and miscellaneous (seven). These data represent the largest series of
      patients with long-term follow-up following stapled anopexy and confirm that the
      operation is safe in experienced hands using appropriate patient selection. The
      early complication rate is low and similar to rates reported for excisional
      hemorrhoidectomy. Importantly, the procedure is associated with a low 3.4% rate
      of reoperation for persistence or recurrence of hemorrhoidal prolapse with good
      patient selection.

PMID- 15951989
TI  - Selective effect of infliximab on the inflammatory component of a colonic
      stricture in Crohn's disease.
AB  - Although infliximab has been shown to improve the clinical course of Crohn's
      disease, its effect on intestinal strictures is controversial. We describe the
      case of a woman with steroid-resistant colonic Crohn's disease presenting with
      intermittent obstruction because of a tight stricture in the splenic flexure.
      Compared with uninvolved areas, biopsies showed intense edema and inflammatory
      cell infiltration and immunohistochemistry revealed an excess of TNF-alpha. Her
      symptoms responded promptly (CDAI went from 444 to 168) to an infliximab infusion
      (10 mg kg(-1) BW), which also had a dramatic effect on the stricture, now
      presenting radiologically as a moderate residual, apparently fibrotic, narrowing
      of the lumen. Endoscopy and histology confirmed the resolution of inflammation
      and TNF-alpha virtually disappeared. The patient refused additional infusions and
      after a few months the disease recurred with features identical to the pre
      treatment phase. She then opted for surgery. Histology of the resected strictured
      colon revealed edema, inflammation, and fibrosis, with TNF-alpha back to pre
      treatment levels. This case indicates that, in the colon, infliximab specifically
      relieves the TNF-alpha-mediated inflammatory component of the stricture while
      having no effect on fibrosis and suggests that the response to infliximab
      treatment may depend on the nature of the, stricture itself.

PMID- 15951990
TI  - Production of the long and short forms of MFG-E8 by epidermal keratinocytes.
AB  - Mouse milk fat globule-EGF factor 8, MFG-E8, is the ortholog to the human mammary
      tumor marker, lactadherin, and comprises two spliced variants, the L and S forms.
      Recent studies have suggested that MFG-E8-L produced by macrophages and
      Langerhans cells in the skin serves as a linker between phagocytic cells and
      apoptotic cells, and that MFG-E8-S, also termed SED1, facilitates sperm-egg
      interaction for fertilization. However, Mfge8 gene expression occurs in various
      tissues apparently unrelated to these critical events. Our in situ hybridization
      study has revealed that Mfge8 is expressed in the periderm (the premature
      epidermis) on embryonic day-14, well before Langerhans cells begin to grow in the
      prenatal phase. Mfge8 transcript is detectable in the basal and spinous layers
      throughout skin development, whereas immunostaining has revealed MFG-E8 protein
      accumulation in the spinous layer. Cultured keratinocyte stem cells consistently
      express Mfge8-L and -S mRNAs and produce the L protein, which is primarily
      detectable in the culture supernatant, and the S protein, which is mostly
      associated with the cells. Upon Ca(2+)-stimulated differentiation, which is
      detected by a decrease in keratinocyte stem cell marker p63(p51) and the
      induction of keratin1, we have observed suppression of Mfge8, and the protein
      becomes localized to the cell-cell borders. Papillomas and carcinomas caused by
      chronic UV-B irradiation produce MFG-E8 as determined by immunostaining. Thus,
      undifferentiated and poorly differentiated keratinocytes produce the L and S
      forms of MFG-E8 during normal and pathological tissue development, probably to
      support an as yet unidentified membrane function.

PMID- 15951991
TI  - Ultrastructural observations of the testicular epithelium and spermatozoa of
      Pseudochordodes bedriagae (Gordiida, Nematomorpha).
AB  - Two questions are of interest concerning the male reproductive system in
      Gordiida: (1) is the epithelium surrounding the testis continuous or
      discontinuous and (2) is the type of spermatozoon as described at the
      transmission electron-microscopical level for the two species of Gordius typical
      for all Gordiida? An examination of the South American species Pseudochordodes
      bedriagae has allowed us to add new information to this poorly studied phylum.
      Testicular tubes are large, filled with spermatozoa, and surrounded by a
      continuous epithelium. The epithelial cells that line the posterior testes
      occasionally overlap, and their cytoplasm is narrow and contains dense granules,
      abundant endoplasmic reticulum, and vesicles. The plasma membrane possesses
      microvilli with many filaments. This epithelium rests on a basement membrane. The
      spermatozoa in P. bedriagae resemble the known spermatozoa of two Gordius species
      but differ in presenting a uniform halo layer of less dense chromatin that
      surrounds the dense chromatin in the nucleus. The finding that a similar type of
      spermatozoa occurs in both genera (Pseudochordodes and Gordius) makes it likely
      that it is present in all other Gordiida and is therefore an autapomorphy of the
      Gordiida.

PMID- 15951992
TI  - Localization and correlation between NADPH-diaphorase and nitric oxide synthase
      isoforms in the porcine uterus during the estrous cycle.
AB  - Nitric oxide (NO), a highly reactive free radical is involved in vasodilation,
      neurotransmission, hormone secretion, and reproduction. Since all known nitric
      oxide synthase (NOS) isoforms possess NADPH-diaphorase (NADPH-d) activity, NADPH
      d histochemistry was used as a commonly accepted procedure for NOS
      identification. The aim of our study was to determine the cellular localization
      of NADPH-d, eNOS, and iNOS in the porcine uterus and the correlation between
      NADPH-d and NOS activity in the early, middle, late luteal, and follicular phase
      of the estrous cycle. Light-microscopic observations of the sections revealed the
      differential expression of the NADPH-d in the analyzed stages of the estrous
      cycle. The most intense staining was observed in the luminal epithelium in the
      late luteal phase and in some groups of the endometrial glands in all studied
      stages. Positive reaction was also found in the endothelial cells of blood
      vessels and in the myometrium itself. Immunostaining for eNOS was observed in the
      luminal and glandular epithelium in all studied stages, but no clear fluctuations
      were observed. The endothelium of both endometrial and myometrial blood vessels
      displayed pronounced eNOS immunostaining. Strong iNOS staining was observed in
      the luminal epithelium in the late luteal and follicular phase and in selected
      groups of endometrial glands. Thus, only NADPH-d and iNOS undergo cyclic changes
      in the studied stages of the estrous cycle. The differential expression of NADPH
      d/NOS in the porcine uterine horn during the estrous cycle suggests a role for NO
      in modulating uterine function.

PMID- 15951993
TI  - Genetic analysis of dry matter and nitrogen accumulation and protein composition
      in wheat kernels.
AB  - The maximum rate and duration for grain dry matter (DM) and nitrogen (N)
      accumulation were evaluated in 194 recombinant inbred lines (RILs) from a cross
      between the two French wheat cultivars Recital and Renan. These cultivars were
      previously identified as having contrasting kinetics of grain DM and N
      accumulation. Grain protein composition was analysed by capillary electrophoresis
      (CE), which enabled quantification of the different storage protein fractions
      (alphabetagamma-gliadins, omega-gliadins, LMW glutenins, HMW glutenins, and each
      of their subunits). Correlation analyses revealed that DM and N accumulation
      rates were closely correlated and repeatable over several years, which was not
      the case for DM and N accumulation durations, and that protein composition was
      primarily influenced by the N accumulation rate. This was particularly true for
      the LMW-glutenins and the alphabetagamma-gliadins, the most abundant protein
      fractions. A genetic map of 254 molecular markers covering nearly 80% of the
      wheat genome was used for quantitative trait loci (QTL) analysis. A total of
      seven QTLs were found. Five QTLs were significantly associated with the kinetics
      of DM and N accumulation, and two of them also influenced protein composition.
      Two QTLs affected only the protein composition. One major QTL explained more than
      70% of the total variation in HMW-GS Glu1B-x content.

PMID- 15951994
TI  - [The "ancient schwannoma". A rare tumor of the mouth floor].
AB  - "Ancient schwannomas" of the mouth floor are rare, benign neoplasms derived from
      the nerve sheath of peripheral nerves. They show many degenerative changes such
      as necrosis and vascular thrombosis. Ancient schwannomas show histopathological
      features, such as degenerative changes and atypical nuclei, and may easily be
      confused with malignant neoplasms. B-scan sonography for the mouth floor and MRT
      imaging may be helpful in differential diagnosis. Here, we report on a patient
      with ancient schwannoma of the floor of the mouth.

PMID- 15951995
TI  - [High speed glottographic diagnostics in laryngology].
AB  - INTRODUCTION: High speed imaging (HSI) allows thousands of pictures to be taken
      of the vibrating vocal folds per second. Although already developed in 1939 in
      the USA, this method only became clinically useful a few years ago as the amount
      of data exceeded the capacity of physical memory. MATERIALS AND METHODS: Rigid
      endoscopes are normally used for high speed glottography. After clinical
      investigation of the patient, kymographic analysis can be carried out off-line.
      Up to 8,000 grayscale images of 256 x 256 pixels can be stored by the Wolf HS
      Endocam 5560 that we used in our study. A maximum of 4,000 images/s can be taken
      by the high speed camera. RESULTS: In high speed glottography, analysis and
      documentation of single vocal fold movements within the vibratory cycle is
      possible. In contrast to stroboscopic investigations, aperiodic movements of the
      vocal folds can be visualized. The duration of a recording differs from 2 to 4 s
      depending on the capture speed. The data transfer to the computer for archiving
      and analysing the images takes a few minutes. CONCLUSION: HSI has advantages and
      disadvantages compared to videoendoscopy and videostroboscopy. The main advantage
      is the visualisation of aperiodic movements, the disadvantages are the transfer
      time for the data and the poorer image quality compared to conventional
      videoendoscopy. Nevertheless HSI is a very promising technique in laryngological
      investigation.

PMID- 15951996
TI  - Reversible posterior leukoencephalopathy syndrome: a changing concept.

PMID- 15951998
TI  - Evaluation of a new Spin-echo diffusion-weighted sequence on a 0.35 T open
      magnetic resonance imaging (MRI)-system: first experiences within 3 h after acute
      stroke.
AB  - In acute stroke, diffusion-weighted magnetic resonance imaging helps to select
      patients who are eligible for thrombolysis, but is almost exclusively implemented
      on closed-bore scanners, which make monitoring of patients difficult. We
      developed and tested a cardiac gated Spin-echo diffusion-weighted sequence with
      prescan finetrim and motion correction on an open system with 0.35 T. Nineteen
      stroke patients appropriate for thrombolytic therapy by clinical criteria were
      enrolled in a prospective study on an intention-to-treat basis. In all but one
      patient, computed tomography and magnetic resonance imaging including the new
      diffusion-weighted sequence were performed within 3 h after symptom onset. Images
      were evaluated for acute cerebral ischemia and hemorrhage by two radiologists
      blinded to clinical information. Magnetic resonance imaging required a mean total
      acquisition time of 26 min. Sensitivity for early infarction was 94% in diffusion
      weighted imaging and 73% in computed tomography. Six patients were excluded from
      thrombolysis due to an infarct size of more than 1/3 of the territory of the
      middle cerebral artery exclusively diagnosed with diffusion-weighted imaging.
      Hemorrhage was recognised by both, magnetic resonance imaging and computed
      tomography. We conclude that in acute stroke, diffusion-weighted imaging with an
      open system at 0.35 T is practicable. The implemented sequence reliably
      demonstrated the size of the infarction and improved the selection of patients
      who are eligible for thrombolysis.

PMID- 15951997
TI  - Intraoperative MRI to guide the resection of primary supratentorial glioblastoma
      multiforme--a quantitative radiological analysis.
AB  - Patients with supratentorial high-grade glioma underwent surgery within a
      vertically open 0.5-T magnetic resonance (MR) system to evaluate the efficacy of
      intraoperative MR guidance in achieving gross-total resection. For 31 patients,
      preoperative clinical data and MR findings were consistent with the putative
      diagnosis of a high-grade glioma, in 23 cases in eloquent regions. Tumor
      resections were carried out within a 0.5-T MR SIGNA SP/i (GE Medical Systems,
      USA). The resection of the lesion was carried out using fully MR compatible
      neurosurgical equipment and was stopped at the point when the operation was
      considered complete by the surgeon viewing the operation field with the
      microscope. We repeated imaging to determine the residual tumor volume only
      visible with MRI. Areas of tissue that were abnormal on these images were
      localized in the bed of resection by using interactive MR guidance. The procedure
      of resection, imaging control and interactive image guidance was repeated where
      necessary. Almost all tissue with abnormal characteristics was resected, with the
      exception of tissue localized in eloquent brain areas. The diagnosis of
      glioblastoma was confirmed in all 31 cases. When comparing the tumor volume
      before resection and at the point where the neurosurgeon would otherwise have
      terminated surgery ("first control"), residual tumor tissue was detectable in
      29/31 patients; the mean residual tumor volume was 30.7 +/- 24%. After repeated
      resections under interactive image guidance the mean residual tumor volume was
      15.1%. At this step we found tumor remnants only in 20/31 patients. The
      perioperative morbidity (12.9%) was low. Twenty-seven patients underwent
      sufficient postoperative radiotherapy. We found a significant difference
      (log(rank)p = 0.0037) in the mean survival times of the two groups with complete
      resection (n = 10, median survival time 537 days) and incomplete resection (n =
      17, median survival time 237 days). The resection of primary glioblastoma
      multiforme under intraoperative MR guidance as demonstrated is a possibility to
      achieve a more complete removal of the tumor than with conventional techniques.
      In our small but homogeneous patient group we found an increase in the median
      survival time in patients with MRI for complete tumor resection, and the overall
      surgical morbidity was low.

PMID- 15951999
TI  - Molecularly-imprinted polypyrrole-modified stainless steel frits for selective
      solid phase preconcentration of ochratoxin A.
AB  - A molecularly-imprinted polymer (MIP) was prepared by electropolymerization of
      pyrrole (Py) onto a stainless steel frit, using ochratoxin A (OTA) as the
      template, in order to make a micro solid phase preconcentration (microSPP)
      device. The OTA template was removed with 1% triethylamine (TEA) in methanol.
      Compared to non-imprinted polypyrrole (PPy), the molecularly-imprinted
      polypyrrole (MIPPy) enhanced the selective binding of OTA. The percentage
      recovery improved from 0 to 40% when the OTA sample solution was acidified with 1
      M HCl (1% by volume). At a flow rate of 0.2 mL/min, maximum OTA binding was
      reached in 6 min after a total loading of 3.2 ng OTA. Final elution of the OTA
      was analyzed by high performance liquid chromatography (HPLC) with fluorescence
      detection, using 20:80 v/v acetonitrile-ammonia buffer (NH4Cl/NH3, 20 mM, pH 9.2)
      as the mobile phase. The MIPPy-microSPP-HPLC results clearly demonstrated that
      the MIPPy-microSPP device afforded selective preconcentration of OTA from red
      wine samples, at OTA concentration levels as low as 0.05 ppb, prior to HPLC
      analysis.

PMID- 15952000
TI  - Investigating the binding interaction of azur A with hyaluronic acid via
      spectrophotometry and its analytical application.
AB  - The interaction between azur A (AA) and hyaluronic acid (HA) at AA concentrations
      from 3.430 x 10(-5) to 8.575 x 10(-5) M and sodium chloride concentrations from 0
      to 0.01 M was investigated spectrophotometrically at 620 nm at temperatures from
      0 to 50 degrees C. AA was shown to be a useful spectroscopic probe for detecting
      carboxyl groups in HA macromolecules. The interaction between AA and HA was
      temperature sensitive and little AA-HA interaction was observed at temperatures
      higher than 30 degrees C. The interaction of HA with AA was seen to be
      electrostatic in nature. The maximum binding number decreased with decreasing
      NaCl concentration, and the absorbance sensitivity decreased with increasing NaCl
      concentration in aqueous solution. Self-interference from the AA in the AA-HA
      interaction caused an overestimate of the molar mass of hyaluronic acid. An
      improved method was proposed to estimate the molar mass of HA, and a molar mass
      of 1.219 x 10(6) Da was obtained with this improved method for HA.

PMID- 15952001
TI  - Determination of oxaliplatin in human plasma and plasma ultrafiltrate by graphite
      furnace atomic-absorption spectrometry.
AB  - A method for sensitive determination of the anti-cancer agent oxaliplatin in
      human plasma and human plasma ultrafiltrate (pUF) is presented. The method is
      based on the quantification of platinum by graphite-furnace atomic-absorption
      spectrometry, with Zeeman correction and an atomisation temperature of 2,700
      degrees C. Sample pretreatment involves dilution of the samples with a solution
      containing 0.15 mol L(-1) NaCl and 0.20 mol L(-1) HCl in water. Validation was
      performed in accordance with the most recent FDA guidelines for bioanalytical
      method validation. All results were within requirements. The validated ranges of
      quantification were 0.10-400 micromol L(-1) for human pUF and 0.50-400 micromol
      L(-1) for plasma. The assay is now successfully used to support pharmacokinetic
      studies of cancer patients treated with oxaliplatin.

PMID- 15952002
TI  - Building a professional career. Ethics--doing the right things.

PMID- 15952003
TI  - Diagnostic Raman spectroscopy for the forensic detection of biomaterials and the
      preservation of cultural heritage.
AB  - This paper reviews the contributions of analytical Raman spectroscopy to the non
      destructive characterisation of biological materials of relevance to forensic
      science investigations, including the sourcing of resins and the identification
      of the biodegradation of art and archaeological artefacts. The advantages of
      Raman spectroscopy for non-destructive analysis are well-appreciated; however,
      the ability to record molecular information about organic and inorganic species
      present in a heterogeneous specimen at the same time, the insensitivity of the
      Raman scattering process to water and hydroxyl groups, which removes the
      necessity for sample desiccation, and the ease of illumination for samples of
      very small and very large sizes and unusual shapes are also apparent. Several
      examples are used to illustrate the application of Raman spectroscopic techniques
      to the characterisation of forensic biomaterials and for the preservation of
      cultural heritage through case studies in the following areas: wall-paintings and
      rock art, human and animal tissues and skeletal remains, fabrics, resins and
      ivories.

PMID- 15952004
TI  - Radio frequency glow discharge source with integrated voltage and current probes
      used for sputtering rate and emission yield measurements at insulating samples.
AB  - Radio frequency glow discharge optical emission spectroscopy (RF-GD-OES) is
      routinely used for the chemical analysis of solid samples. Two independent
      electrical signals from the discharge are required for quantification. When
      sputtering insulating samples, the voltage over the discharge is not directly
      measurable. The coupling capacity of the sample is required in order to calculate
      the discharge voltage. A procedure is outlined where the coupling capacity is
      determined using an electrical measurement without discharge. The calculated time
      dependent discharge voltage and current are evaluated using a plasma equivalent
      circuit. An insulating sample is sputtered at constant cathode voltage and
      current. The emission yield for an aluminium line is comparable to that of
      conducting reference material.

PMID- 15952005
TI  - Clinical outcome of the arthroscopic management of sports-related "anterior ankle
      pain": a prospective study.
AB  - Anterior impingement syndrome is a generally accepted diagnosis for a condition
      characterized by anterior ankle pain with limited and painful dorsiflexion. The
      cause can be either soft tissue or bony obstruction. We reviewed 26 (16 male and
      10 female) athletes with a mean age of 27 years treated arthroscopically for
      symptoms due to soft-tissue (group I, n = 12) and bony obstruction (group II, n =
      14). They suffered from anterior pain, reduction of dorsiflexion and recurrent
      swelling with severe impairment in their sports activities. There was no clinical
      improvement for at least 6 months despite of conservative treatment with a mean
      duration of symptoms about 20 months. There were no further operations.
      Evaluation included the Karlsson ankle rating score, the activity score of
      Tegner, and a visual analogue scale (VAS) reflecting patients' pain. Conventional
      radiographs and Magnetic resonance imaging (MRI) were done preoperatively. All
      patients were available for follow up after 31 months (range, 25-48 months) with
      a significant improvement (p < 0.05) of the Karlsson score from 66 to a mean of
      92 at the follow-up examination. The mean Tegner score was eight points compared
      to three points preoperatively. Regarding the subjective assessment observed by
      the decrease of pain and the ability of the athelete to return to competition
      sport, there were 25 very satisfied and one unsatisfied athlete. No significant
      difference in the outcome of group I and II (p > 0.05) could be estimated. The
      results demonstrate ' excellent ' to ' good ' results for arthroscopic treatment
      of sports-related anterior ankle pain in a group of athletes who were involved in
      competition sport. The promising clinical results confirm an effective way of
      treating soft-tissue and bony impingement. In addition, we recommend prior to
      surgery, an adequate course of non-operative treatment, including modifications
      in the exercise program and athletic activity.

PMID- 15952006
TI  - Tendoscopic debridement for stage I posterior tibial tendon dysfunction.
AB  - Our objective is to assess whether the tendoscopic synovectomy is effective to
      control the stage I posterior tibial tendon dysfunction. Our study is a
      retrospective one. The participants, six patients with stage I posterior tibial
      tendon dysfunction, were treated with tendoscopy with synovectomy for the past 3
      years. The results show that this is a safe procedure and we could achieve
      similar effectiveness as the traditional open procedure. There was no
      complication found. None of our patients have progressed to stage II or above
      posterior tibial tendon dysfunction. In conclusion, tendoscopic debridement is a
      minimal invasive surgery. It is effective to control the stage I posterior tibial
      tendon dysfunction. In addition, it had the advantages of smaller scars, less
      wound pain and a short hospital stay.

PMID- 15952007
TI  - In vitro reproduction of clinical hallmarks of eczematous dermatitis in
      organotypic skin models.
AB  - Dermatitis is a group of highly pruritic chronic inflammatory skin diseases which
      represents a major public-health problem worldwide. The prevalence of dermatitis
      has increased in recent years affecting up to 20% of the general population.
      Acute skin lesions are characterized by extensive degrees of intercellular edema
      of the epidermis (spongiosis) and a marked perivenular inflammatory cell
      infiltrate in the dermis. Keratinocytes within eczematous lesions exhibit a
      modified expression of proinflammatory cytokines, chemokines and cell-surface
      molecules. The pathophysiological puzzle of dermatitis is far from being
      elucidated completely, but skin infiltration of activated memory/effector T cells
      are thought to play the pivotal role in the pathogeneses. The aim of this study
      was the set-up of organotypic models mimicking the symptoms of eczematous
      dermatitis to provide a tool for therapeutic research in vitro. Therefore
      activated T cells (ATs) were integrated in organotypic skin and epidermis
      equivalents (SE, EE). These models enabled the reproduction of several clinical
      hallmarks of eczematous dermatitis: (1) T cells induce keratinocyte apoptosis,
      which leads to a reduced expression of the adhesion molecule E-cadherin (E-cad)
      and disruption of the epidermal barrier. (2) Expression of intercellular adhesion
      molecule-1 (ICAM-1) allows the attachment of leukocytes to epidermal cells. (3)
      Upregulation of neurotrophin-4 (NT-4) in the epidermis is thought to mediate
      pruritus in lesions by supporting nerve outgrowth. (4) Elevated levels of pro
      inflammatory cytokines (IL-1alpha and IL-6) and chemokines (IL-8, IP-10, TARC,
      MCP-1, RANTES and eotaxin) amplify the inflammatory response and lead to an
      influx of secondary immunocells into the skin. The therapeutics dexamethasone and
      FK506 markedly reduce cytokines/chemokines production and epidermal damaging in
      these models. These data underline that activated memory/effector T cells induce
      eczematous changes in this HaCaT cell based organotypic skin equivalent.
      Furthermore it can be concluded that these models make it possible to investigate
      targets of therapeutics in skin.

PMID- 15952008
TI  - [The alpha2delta subunit of the voltage-dependent calcium channel. A new
      pharmaceutical target for psychiatry and neurology].
AB  - Calcium channel blockers are substances used for treating high blood pressure and
      coronary heart disease. New medications have been developed that modulate calcium
      channels but also show promise in psychiatric and neurologic applications.
      Gabapentin and pregabalin bind to a subunit of calcium channels--the alpha2delta
      receptors--thereby reducing calcium influx to neurons. As a result, less
      glutamate is released from nerve endings that use excitatory amino acids as
      transmitters. This in turn reduces substance P-related activation of AMPA
      heteroreceptors on noradrenergic synapses, total transmitter release, and finally
      neuronal activity. That mechanism is the probable explanation for gabapentin's
      and pregabalin's usefulness in the treatment of neuropathic pain but also their
      possible anticonvulsive and anxiolytic effects.

PMID- 15952009
TI  - No pain relief from morphine? Individual variation in sensitivity to morphine and
      the need to switch to an alternative opioid in cancer patients.
AB  - GOALS OF WORK: The aims of this study were (1) to prospectively evaluate the
      clinical benefits of switching from morphine to an alternative opioid, using
      oxycodone as first-line alternative opioid, in patients with cancer, (2) to
      evaluate the consistency of the clinical decision for the need to switch by
      comparing two hospital sites, and (3) to evaluate whether there were objective
      predictors that would help identify morphine non-responders who require switching
      to an alternative opioid and from this to construct a clinical model to predict
      the need to switch. PATIENTS AND METHODS: One hundred eighty-six palliative care
      patients were prospectively recruited from two hospital sites. Responders were
      patients treated with morphine for more than 4 weeks with good analgesia and
      minimal side effects. Non-responders (switchers) were patients who had either
      uncontrolled pain or unacceptable side effects on morphine and therefore required
      an alternative opioid. The differentiation between responders and switchers was
      made clinically and later confirmed by objective parameters. RESULTS: In this
      prospective study 74% (138/186) had a good response to morphine (responders). One
      patient was lost to follow up. Twenty-five percent (47/186) did not respond to
      morphine. These non-responders were switched to alternative opioids (switchers).
      Furthermore, of 186 patients, 37 achieved a successful outcome when switched to
      oxycodone and an additional 4 were well controlled when switched to more than one
      alternative opioid. Overall successful pain control with minimal side effects was
      achieved in 96% (179/186) of patients. There were no significant differences in
      the need to switch between the two hospital sites. CONCLUSIONS: This study has
      shown that proactive clinical identification and management of patients that
      require opioid switching is reproducible in different clinical settings and
      significantly improves pain control. Further studies are required to develop and
      test the predictive model.

PMID- 15952010
TI  - Investigation and management of an epidemic of Hydroview intraocular lens
      opacification.
AB  - BACKGROUND: Opacification of Hydroview posterior chamber intraocular lenses had
      been prescribed, but many aspects of this complication remain unknown, including
      its aetiology, clinical features, pathogenesis, prognosis and treatment. This
      paper describes an epidemic of Hydroview intraocular lens (IOL) opacification.
      METHODS: Subjects in whom the Hydroview IOL was implanted were recalled for
      evaluation of its transparency, assessment of contrast sensitivity (CS) [VCTS
      (Vistech CO, Dayton, Ohio, USA)] and visual acuity (LogMAR), and analysis of
      medical and surgical data. The results of IOL exchange in 69 eyes of 67 patients
      are also presented. RESULTS: Of 103 patients recalled, 46 (44.6%) and 3 (2.9%)
      exhibited opacification of the implanted IOL in one and both eyes, respectively.
      CS was significantly worse in the presence of an opacified IOL (P<0.050), even
      when Snellen acuity was unaffected. Where the viscoelastic employed during the
      primary cataract surgery was reliably documented, VISCOAT was used in 100% of
      cases (43/43), whereas Healonid had not been used in any (0/57) (P<0.0001).
      Following IOL exchange, visual acuity improved from a mean (+/-SD) of 0.75 (0.41)
      to 0.4 (0.34) LogMAR. CONCLUSIONS: The prevalence of Hydroview IOL opacification
      is associated with the use of VISCOAT in the primary cataract surgery, and there
      is a biochemically plausible rationale to account for this. Visual acuity and
      contrast sensitivity are adversely affected by opacification of the Hydroview
      IOL, but CS to a greater extent. Exchange of opaque IOLs is a visually rewarding
      procedure.

PMID- 15952011
TI  - Screening, mutagenesis and protoplast fusion of Aspergillus niger for the
      enhancement of extracellular glucose oxidase production.
AB  - Various strains of Aspergillus niger were screened for extracellular glucose
      oxidase (GOD) activity. The most effective producer, strain FS-3 (15.9 U mL(-1)),
      was mutagenized using UV-irradiation or ethyl methane sulfonate. Of the 400
      mutants obtained, 32 were found to be resistant to 2-deoxy D: -glucose, and 17 of
      these exhibited higher GOD activities (from 114.5 to 332.1%) than the original FS
      3 strain. Following determination of antifungal resistance of the highest
      producing mutants, four mutants were selected and used in protoplast fusions in
      three different intraspecific crosses. All fusants showed higher activities (from
      285.5 to 394.2%) than the original strain. Moreover, of the 30 fusants isolated,
      19 showed higher GOD activity than their corresponding higher-producing parent
      strain.

PMID- 15952012
TI  - [Protocol based ventilator weaning strategy or individual medical decision?].

PMID- 15952013
TI  - [Reconstructive urology--renaissance of surgery?].

PMID- 15952014
TI  - [In vitro stratified urothelium and its relevance in reconstructive urology].
AB  - There are two main objectives regarding tissue engineering in reconstructive
      urology: (1) to provide the surgeon with autologous tissue for urogenital
      reconstructive purposes and (2) to create the framework for experimental
      investigations to better understand the structure and function of the tissues
      involved. In the last years urothelial cell culture has become a routine
      laboratory technique. There is sufficient cellular output after isolation and
      propagation to seed cells as single cell suspensions on biodegradable matrices
      for the construction of cell-matrix implants. In recent publications attention
      was directed toward using established primary cell cultures for in vitro
      stratification of multilayered urothelial sheets. Urothelial sheets have been
      used quite successfully for covering acellular matrices for bladder augmentation
      in dog and minipig models. However, up to now there has been no clinical
      application in humans of urothelial sheets generated in vitro. Here we review
      facts about the different strategies for generating multilayered urothelial
      sheets.

PMID- 15952015
TI  - [Nerve repair strategies for restoration of erectile function after radical
      pelvic surgery].
AB  - Iatrogenic cavernous nerve lesions occurring during radical pelvic surgery often
      lead to irreversible erectile dysfunction. The nerve defects after excision of
      the neurovascular bundles must be reconstructed by interposition grafting to
      supply a permissive scaffold for oriented axonal regrowth. The use of autologous
      nerve grafts for the repair of human cavernous nerves during radical
      prostatectomy has been controversial regarding the limited success achieved with
      bilateral nerve grafting. Artificial nerve guides consisting of natural or
      synthetic materials have been successfully used for bridging peripheral nerve
      defects. The combination with Schwann cells, neurotrophic factors and
      extracellular matrix components has been shown to promote cavernous nerve
      regeneration.

PMID- 15952016
TI  - The influence of arbuscular mycorrhizae and light on Wisconsin (USA) sand savanna
      understories 1. Plant community composition.
AB  - To explain the complex community composition found in Wisconsin (USA) oak
      savannas, we investigated potentially interacting effects of light gradients and
      arbuscular mycorrhizal fungi (AMF) on community composition in the greenhouse,
      using a fully randomized block experimental design. We used plant species, soil,
      and AMF from a remnant sand savanna in setting up the experiment, using two light
      and five AMF treatments. Eleven plant species were seeded into 80 microcosms, and
      they were grown together for 20 weeks. Plant numbers and biomass were measured,
      and Simpson's index was calculated for both. Data were analyzed using ANOVA and
      nonparametric ANOVA. We found significant light effects on biomass and on numbers
      of four species. There were no treatment effects on Simpson's index, and only
      Schizachyrium numbers showed a significant AMF effect. These findings are
      consistent with results from other studies of the sand savanna, and,
      collectively, these data suggest that plant community composition in this species
      rich savanna is not strongly influenced by arbuscular mycorrhizae. This is a
      novel finding with important implications for understanding interactions between
      plant and AMF diversity in wild communities.

PMID- 15952017
TI  - Experimental muscle pain changes motor control strategies in dynamic
      contractions.
AB  - This study investigated the effect of muscle pain on muscle activation strategies
      during dynamic exercises. Ten healthy volunteers performed cyclic elbow
      flexion/extension movements at maximum speed for 2 min after injection of (1)
      hypertonic (painful) saline in the biceps brachii, (2) hypertonic saline in both
      biceps brachii and triceps brachii, and (3) isotonic (nonpainful) saline in the
      biceps brachii muscle. Surface electromyographic (EMG) signals were collected
      from the upper trapezius, biceps brachii, triceps brachii, and brachioradialis
      muscles (to estimate EMG amplitude) and with an electrode arrays from biceps
      brachii (to estimate muscle fiber conduction velocity [CV]). In all conditions,
      the acceleration of the movement decreased throughout the exercise, and kinematic
      parameters were not altered by pain. With respect to the control condition, pain
      induced a decrease of the biceps brachii (mean +/- SE, -23+/-4%) and
      brachioradialis (-10+/-0.4%) integrated EMG (IEMG) in the beginning of the
      exercise, and an increase (45+/-3.5%) of the upper trapezius IEMG at all time
      points during the exercise. The biceps brachii IEMG decreased over time during
      the nonpainful exercises (-11+/-0.6%) while it remained constant in the painful
      condition. Biceps brachii CV decreased during painful conditions (-12.8+/-2.2%)
      while it remained constant during the nonpainful condition. In conclusion, muscle
      pain changes the motor control strategy to sustain the required dynamic task both
      in the relative contribution between synergistic muscles and in the motor unit
      activation within the painful muscle. Such a changed motor strategy may be highly
      relevant in models of occupational musculoskeletal pain conditions.

PMID- 15952018
TI  - Order parameters of unsaturated phospholipids in membranes and the effect of
      cholesterol: a 1H-13C solid-state NMR study at natural abundance.
AB  - Most biological phospholipids contain at least one unsaturated alkyl chain.
      However, few order parameters of unsaturated lipids have been determined because
      of the difficulty associated with isotopic labeling of a double bond. Dipolar
      recoupling on axis with scaling and shape preservation (DROSS) is a solid-state
      nuclear magnetic resonance technique optimized for measuring (1)H-(13)C dipolar
      couplings and order parameters in lipid membranes in the fluid phase. It has been
      used to determine the order profile of 1,2-dimyristoyl-sn-glycero-3
      phosphocholine hydrated membranes. Here, we show an application for the
      measurement of local order parameters in multilamellar vesicles containing
      unsaturated lipids. Taking advantage of the very good (13)C chemical shift
      dispersion, one can easily follow the segmental order along the acyl chains and,
      particularly, around the double bonds where we have been able to determine the
      previously misassigned order parameters of each acyl chain of 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC). We have followed the variation of such order
      profiles with temperature, unsaturation content and cholesterol addition. We have
      found that the phase formed by DOPC with 30% cholesterol is analogous to the
      liquid-ordered (l(o)) phase. Because these experiments do not require isotopic
      enrichment, this technique can, in principle, be applied to natural lipids and
      biomembranes.

PMID- 15952019
TI  - Treatment of primary malignant bone tumours of the distal tibia.
AB  - We treated 15 patients with primary malignant bone tumours of the distal tibia of
      which 14 were treated by limb salvage surgery. Reconstructions were done by
      allografts with or without microvascular fibula transfer, by bone transport, by
      fibula transfer alone or by endoprosthetic replacement. The most successful
      methods were bone transport and endoprosthetic replacement. However, serious
      complications with deep infections leading to secondary amputation occurred in
      four patients and in all reconstruction groups. After a mean follow up of 7
      years, no local recurrence occurred, and all patients were alive and free of
      disease. After radical resection, bone transport in defects less than 15 cm is a
      viable option. In larger defects in children, allograft with vascularised fibula
      is an acceptable alternative, but amputation still has a role in this group. In
      adults, endoprosthetic replacement with proper soft tissue coverage is a viable
      option in cases with large bony defects.

PMID- 15952020
TI  - Thiopurine S-methyltransferase as a target for drug interactions.
AB  - OBJECTIVE: The present study was undertaken to investigate the possible effects
      of various agents on thiopurine methyltransferase (TPMT) activity in red blood
      cells (RBCs) from patients with chronic inflammatory bowel disease (IBD).
      METHODS: In three groups of patients with very high, normal and intermediate TPMT
      activity (each n=6), the inhibitory potential of furosemide, piretanide,
      azathioprine (AZA) and testosterone was assessed by ex vivo measurements of TPMT
      activity in RBCs. From individual concentration-response curves, IC50 values have
      been determined. RESULTS: Independent of the basal TPMT activity, lowest IC50
      values were calculated for furosemide (15-19 microM), followed by testosterone
      (30-72 microM), piretanide (300-313 microM) and AZA (430-532 microM). Compared
      with reported plasma concentration achieved during treatment, only furosemide
      would have the potential to inhibit TPMT also in vivo, whereas the IC50 values of
      the other agents are far above the corresponding plasma levels. CONCLUSIONS: Our
      ex vivo study revealed that only furosemide has the potential to inhibit TPMT
      activity in patients with IBD. This possibility should be taken into
      consideration if the diuretic and AZA or 6-mercaptopurine are coadministered.
      However, the extrapolation to the clinical setting remains open.

PMID- 15952021
TI  - Frequent prescribing of drugs with potential gastrointestinal toxicity among
      continuous users of non-steroidal anti-inflammatory drugs.
AB  - OBJECTIVE: A number of drugs used concurrently with non-steroidal anti
      inflammatory drugs (NSAIDs) increase the risk of gastrointestinal (GI)
      haemorrhage. We studied the prescribing of NSAIDs with corticosteroids, oral
      anticoagulants or selective serotonin re-uptake inhibitors (SSRIs), as well as
      the use of gastroprotection among continuous and non-continuous users of NSAIDs
      in Finland. METHODS: Concurrent use of various drugs was analysed in a nested
      case-control study in a population-based cohort of NSAID users in 2000 using data
      in the National Prescription Database. RESULTS: Prescribing of any other drug
      with the potential to increase the risk of GI bleeding with NSAIDs was five times
      [5.2; 95% confidence interval (CI) 4.7-5.9] more common among continuous than non
      continuous NSAID users, and the odds ratio for oral corticosteroids was 8.0 (95%
      CI 6.6-9.6). Of patients using continuous NSAIDs with oral corticosteroids, 73.3%
      had rheumatoid arthritis (RA). After excluding RA patients, the odds ratio
      remained high (4.5; 95% CI 3.3-6.1) and at the same level as for SSRIs (3.7; 3.1
      4.4). Gastroprotective drugs were prescribed for 6.8% of the continuous users of
      NSAIDs alone, and for 20.4% of patients taking any of the studied drug
      combinations with NSAIDs. The continuous users of NSAIDs alone had
      gastroprotection 2.9 (2.5-3.3) times more often than other users of NSAIDs. With
      drug combinations (NSAID+corticosteroid, NSAID+SSRI, NSAID+anticoagulants), the
      use of gastroprotection did not differ from patients using lower amounts of
      NSAIDs. CONCLUSIONS: When prescribing NSAIDs, situations leading to habitual use
      should be avoided, potential complications due to clustering of risk factors
      recognised, and gastroprotection prescribed for patients with increased risk of
      GI haemorrhage.

PMID- 15952022
TI  - Warfarin dose related to apolipoprotein E (APOE) genotype.
AB  - OBJECTIVE: Warfarin is an anticoagulant which acts through interference with the
      recycling of vitamin K in the liver, leading to reduced activation of several
      clotting factors. Apolipoprotein E plays a central role in the uptake of the
      lipid-soluble vitamin K. The apolipoprotein E (APOE) alleles E2, E3 and E4 encode
      the three major isoforms of apolipoprotein E. The aim of this project was to
      evaluate whether variation in the APOE gene influences warfarin dose. METHODS: We
      genotyped APOE in 183 warfarin-treated patients. Information about warfarin dose,
      prothrombin time, age, gender, body weight, treatment indication and duration,
      other diseases and concurrent medication was taken from the patients' medical
      records. Cytochrome P450 2C9 genotyping had been performed previously, and
      patients were stratified according to CYP2C9 genotype. RESULTS: Patients
      homozygous for APOE*E4 tended to receive higher warfarin doses than others. Among
      CYP2C9 extensive metabolisers, APOE*E4 homozygous patients received significantly
      higher warfarin doses than patients with one or no E4 alleles; 56.9 compared with
      34.3 and 34.6 mg/week, (Bonferroni corrected P=0.008 and 0.007, respectively).
      APOE genotype explains 6% of warfarin dose variance among CYP2C9 extensive
      metabolisers (analysis of variance, P=0.009). CONCLUSION: Previous studies have
      shown that individuals carrying the APOE*E4 allele have a faster uptake of
      lipoproteins into the liver and lower levels of circulating vitamin K than
      others. It is therefore plausible that patients carrying E4 alleles have an
      enhanced uptake of vitamin K into the liver and require higher doses of warfarin
      to compensate for this.

PMID- 15952023
TI  - [Teleradiology and PACS--strategy of the Innsbruck University Hospital].
AB  - Systems for management of digital imaging data are very important and widespread
      at the Innsbruck University Hospital and constitute a central component of the IT
      strategies followed by the hospital operating company TILAK (Tyrolean public
      hospitals). The particular goal is to integrate all imaging data into the
      electronic medical records and make these available online to each of the approx.
      2500 clinic workstations and ensure electronic data exchange with other
      healthcare services. Teleradiology connections have been established at the
      University Clinic for Radiology since 1995; these have been continually expanded
      and linked to the central PACS. An eHealth web portal was recently established to
      facilitate transfer of images and findings from TILAK hospitals to other
      healthcare organizations. Registered users can be cleared for a limited time to
      access all radiological imaging data via this web portal.

PMID- 15952024
TI  - Temperature dependence of soleus H-reflex and M wave in young and older women.
AB  - The purpose of this study was to investigate the effect of altered local
      temperature on soleus H-reflex and compound muscle action potential (M wave) in
      young and older women. H-reflex and M wave responses were elicited in 10 young
      (22.3 +/- 3.3 years) and 10 older (72.5 +/- 3.2 years) women at three muscle
      temperatures: control (34.2 +/- 0.3 degrees C), cold (31.3+/-0.5 degrees C) and
      warm (37.1 +/- 0.2 degrees C). H-reflex output, expressed as the ratio between
      maximal H-reflex and maximal M wave (H(max)/M(max)), was lower in the older,
      compared with the younger, group, regardless of temperature. In control
      temperature conditions, for example, the H(max)/M(max) ratio was 36.8 +/- 24% in
      the young and 25.4 +/- 20% in the older (P<0.05). Warming had no effect on the H
      reflex output in either group, whilst cooling increased H-reflex output only in
      the younger group (+28%). In both groups, cooling increased (+5.3%), and warming
      decreased (-5.5%) the H-reflex latency. This study confirms that older
      individuals experience a reduced ability to modulate the reflex output in
      response to a perturbation. In a cold environment, for example, the lack of
      facilitation in the reflex output, along with a delayed reflex response could be
      critical to an older individual in responding to postural perturbations thus
      potentially compromising both static and dynamic balance.

PMID- 15952025
TI  - Voluntary wheel-running exercise enhances antigen-specific antibody-producing
      splenic B cell response and prolongs IgG half-life in the blood.
AB  - Exercise has been recognized to provoke upregulation of antibodies. However, the
      mechanism has not been explained. We examined the effects of voluntary wheel
      running exercise on the number of cells which produce tetanus toxoid (TT)
      specific IgG, as well as serum level and clearance of administered 125I-labeled
      mouse IgG in the blood. Male C57BL/6N mice were randomly divided into a voluntary
      wheel-running exercise group and a sedentary group. Mice were intraperitoneally
      immunized with 0.375 microg/kg of TT to induce primary and secondary anti-TT
      antibody responses. ELISPOT assays that identified TT-specific antibody
      production were performed on day 0 (Baseline, n = 8) and 22 (EX: n = 8, Non-EX: n
      = 8) after initial immunization (primary response) and on day 32 (EX: n = 8, Non
      EX: n = 7) and 43 (EX: n = 7, Non-EX: n = 7). To explain why serum TT-specific
      IgG was elevated in the exercise group, we conducted an 125I-labeled mouse IgG
      clearance test on day 32. ELISPOT counts of secondary responses to TT
      immunization were significantly higher in the running group than in the sedentary
      group (P<0.05). The serum anti-TT specific IgG concentration was also
      significantly higher in the running group (P<0.05) than in the sedentary on day
      32. The values of both groups were relatively lower on day 43. The (125)I-labeled
      mouse IgG was more rapidly cleared in the non-exercised than in the exercised
      group (P<0.05). These results show that voluntary wheel running upregulates the
      TT-specific humoral immune response. These reactions may be partly explained by
      the accelerated induction of TT-specific IgG-producing cells and prolonged serum
      IgG half-life with voluntary exercise.

PMID- 15952026
TI  - Myofascial force transmission in dynamic muscle conditions: effects of dynamic
      shortening of a single head of multi-tendoned rat extensor digitorum longus
      muscle.
AB  - This study investigated the effects of myofascial force transmission during
      dynamic shortening of head III of rat extensor digitorum longus muscle (EDL III).
      The anterior crural compartment was left intact. Force was measured
      simultaneously at the distal EDL III tendon, the proximal EDL tendon and the
      distal tendons of tibialis anterior and extensor hallucis longus muscles (TA +
      EHL). Two types of distal shortening of EDL III were studied: (1) sinusoidal
      shortening (2 mm) and (2) isokinetic shortening (8 mm). Sinusoidal shortening of
      EDL III caused a decrease in force exerted at the distal tendon of EDL III: from
      0.58 (0.08) N to 0.26 (0.04) N. In contrast, hardly any changes in proximal EDL
      force and distal TA+EHL force were found. Maximal concentric force exerted at the
      distal tendon of EDL III was higher than maximal isometric force expected on the
      basis of the physiological cross-sectional area of EDL III muscle fibers (Maas et
      al. 2003). Therefore, a substantial fraction of this force must originate from
      sources other than muscle fibers of EDL III. Isokinetic shortening of EDL III
      caused high changes in EDL III force from 0.97 (0.15) N to zero. In contrast,
      changes in proximal EDL force were much smaller: from 2.44 (0.25) N to 1.99
      (0.19) N. No effects on TA + EHL force could be shown. These results are
      explained in terms of force transmission between the muscle belly of EDL III and
      adjacent tissues. Thus, also in dynamic muscle conditions, muscle fiber force is
      transmitted via myofascial pathways.

PMID- 15952028
TI  - Individualized treatment of craniopharyngioma in children: ways and means.
AB  - BACKGROUND: Medium- and long-term prognosis of craniopharyngioma is overwhelmed
      by the risks of hypothalamic and visual impairment. This problem has been
      underestimated for a long time because the major concern for the neurosurgeon was
      the risk of recurrences, their best prevention being thought to be complete
      tumour resection. Today, we know that radical surgery not only is not an absolute
      guarantee against recurrences but also can cause hypothalamic and visual
      complications. METHODS: The authors suggest that instead of complete removal, the
      first choice treatment should be, when possible, a less aggressive, multistaged
      and personalized treatment. In this perspective they focus on other therapeutic
      methods: endocavity treatment of cysts with rhenium-186, triconformational
      radiotherapy, radiosurgery, and widespread use of the trans-sphenoidal approach.
      CONCLUSIONS: These simple methods should reduce the risks of visual aggravation
      and metabolic syndrome.

PMID- 15952029
TI  - Placement of baclofen pumps through the foramen magnum and upper cervical spine.
AB  - INTRODUCTION: The baclofen pump has been utilized in children with refractory
      spasticity. However, in children with prior lumbar fusion, the implantation of
      such a device is difficult and fraught with complications. As an alternative to
      placing the pump catheter through the lumbar spine, we report our experience with
      placement of the catheter in the spinal canal via a cervical approach through the
      foramen magnum. METHODS: We have followed three patients with prior lumbar fusion
      and refractory spasticity, each of whom has undergone placement of the
      intrathecal component of a baclofen pump via the foramen magnum. Appropriate
      positioning of the catheter tip at the T6 spinal level was determined using
      intraoperative fluoroscopy. The catheter was then tunneled to the pump in the
      abdominal wall. RESULTS: All patients experienced a significant decrease in the
      severity of spasticity with pump placement. The pumps continued to function
      properly over a follow-up period of 24, 24, and 44 months respectively. In one
      patient, the catheter recoiled into the subcutaneous tissues several months after
      its placement, thus necessitating repositioning. One of the pumps was removed 2
      years later secondary to a VP shunt infection. However, there were no immediate
      complications related to placement of the spinal catheter. CONCLUSIONS: Placement
      of the intraspinal component of a baclofen pump via the foramen magnum is a
      viable alternative for patients with spastic quadriparesis with prior lumbar
      fusion. The tip of the spinal catheter can be positioned in the thoracic region
      in a similar manner to the placement traditional lumbar pumps. In our series,
      there were no adverse sequelae related to the surgery or catheter positioning.

PMID- 15952030
TI  - Prediction of independence and intelligence at birth in meningomyelocele.
AB  - OBJECTIVE: The aim of this research is to compute a prediction of the future
      intelligence of every neonate with a meningomyelocele (MMC) on the day of birth
      to inform the parents. Earlier research revealed that the variables ventricle
      size, open arch above vertebra lumbar 3, a very small or a very large head can be
      attended by an IQ below 85 points: the turning point between dependence and
      independence. METHODS: Until now no research has been done combining the values
      of influencing variables in one equation. Our study used the equation of multiple
      longitudinal linear regression. For reference, data from the files of 148
      neonates born in the years 1960-1980 were compared with those of Dutch children
      sampled by Verger. The working hypothesis that the IQ level is directly related
      to congenital deformities of the nervous system needs to be tested. As standard
      the values of variables at birth, the head circumference and length, the size of
      the ventricles and the highest open vertebral arch, are to be used. RESULTS: The
      Wisc-R of the MMC cohort had a mean of 84 points and 55% had an IQ above 85. The
      correlation computation of the values of all available variables with the values
      of the measured Wisc-R revealed the significance of the neuroanatomical
      variables, size of ventricle and level of the highest open vertebral arch and for
      the anthropomorphic variables Length and Length/Circumference. To establish the
      relationship between the Wisc-R value and the values of the significant variables
      an equation with the multiple linear regression method was used. The measured IQ
      is made dependent on the significant variables size of ventricle, level of
      highest open arch and quotient Length by Circumference. This equation produces a
      value called predicted IQ. The predicted IQ was 92%, the same or nearly the same
      as the measured Wisc-R IQ. CONCLUSION: This conformity of the measured IQ and the
      predicted IQ proves the possibility of using these birth data for prediction.

PMID- 15952031
TI  - Contributions of the ubiquitin-proteasome pathway and apoptosis to human skeletal
      muscle wasting with age.
AB  - The primary mechanism that contributes to decreasing skeletal muscle strength and
      size with healthy aging is not presently known. This study examined the
      contribution of the ubiquitin-proteasome pathway and apoptosis to skeletal muscle
      wasting in older adults (n = 21; mean age = 72.76 +/- 8.31 years) and young
      controls (n = 21; mean age = 21.48 +/- 2.93 years). Subjects underwent a
      percutaneous muscle biopsy of the vastus lateralis to determine: (1) ubiquitin
      ligase gene expression (MAFbx and MuRF1); (2) frequency of apoptosis; and (3)
      individual fiber type and cross-sectional area. In addition, a whole muscle
      strength test was also performed. A one-way ANOVA revealed significant increases
      in the number of positive TUNEL cells in older adults (87%; p < 0.05), although
      no significant increase in caspase-3/7 activity was detected. Additionally,
      ubiquitin ligase gene expression, individual muscle fiber type and CSA were not
      different between old and young subjects. Muscle strength was also significantly
      lower in old compared to young subjects (p < 0.05). In conclusion, this study
      indicates a preferential role for apoptosis contributing to decreases in muscle
      function with age.

PMID- 15952033
TI  - TRPV4 as osmosensor: a transgenic approach.
AB  - The transient receptor potential vanilloid 4 (TRPV4) ion channel was named
      initially vanilloid-receptor-related osmotically activated channel (VR-OAC).
      Preliminary answers to the question, "What is the function of the trpv4 gene in
      live animals ?" are highlighted briefly in this review. In trpv4 null mice, TRPV4
      is necessary for the maintenance of osmotic equilibrium, and in Caenorhabditis
      elegans transgenic for mammalian TRPV4, TRPV4 directs the osmotic avoidance
      response in the context of the ASH "nociceptive" neuron. The molecular mechanisms
      of gating of TRPV4 in vivo need to be determined; in particular, whether TRPV4 in
      live animals is gated via phosphorylation of defined amino-acid residues or more
      directly through the osmotic stimulus itself.

PMID- 15952032
TI  - Mechanisms of actions of guanylin peptides in the kidney.
AB  - After a salty meal, stimulation of salt excretion via the kidney is a possible
      mechanism to prevent hypernatremia and hypervolemia. Besides the well known
      hormonal regulators of salt and water excretion in the distal nephron, arginine
      vasopressin and aldosterone, guanylin (GN) peptides produced in the intestine
      were proposed to be intestinal natriuretic peptides. These peptides inhibit Na+
      absorption in the intestine and induce natriuresis, kaliuresis and diuresis in
      the kidney. The signaling pathway of GN peptides in the intestine is well known.
      They activate enterocytes via guanylate cyclase C (GC-C) and increase the
      cellular concentration of cGMP which leads to secretion of Cl-, HCO3- and water
      into the intestinal lumen and to inhibition of Na+ absorption. Guanylin peptides
      are filtered in the glomerulus, and additionally synthesized and excreted by
      tubular cells. They activate receptors located in the luminal membrane of the
      tubular cells along the nephron. In GC-C deficient mice renal effects of GN
      peptides are retained. In human, rat, and opossum proximal tubule cells, a cGMP
      dependent signaling was demonstrated, but in addition GN peptides apparently also
      activate a PT-sensitive G-protein coupled receptor. A similar dual signaling
      pathway is also known for other natriuretic peptides like atrial natriuretic
      peptide. A cGMP-independent signaling pathway of GN peptides is also shown for
      principal cells of the human cortical collecting duct where the final hormonal
      regulation of electrolyte homeostasis takes place. This review will focus on the
      current knowledge on renal actions of GN peptides and specifically address novel
      GC-C- and cGMP-independent signaling mechanisms.

PMID- 15952034
TI  - No effect of twitchin phosphorylation on the rate of myosin head detachment in
      molluscan catch muscle: are myosin heads involved in the catch state?
AB  - Phosphorylation of twitchin is known to abolish the catch state of anterior
      byssus retractor muscle (ABRM) of the bivalve mollusc Mytilus edulis. To
      investigate the role of myosin head involvement in force maintenance during
      catch, the effect of twitchin phosphorylation on myosin head detachment was
      studied in saponin-skinned fibre bundles of ABRM. The detachment rate of myosin
      heads was deduced from two types of experiments: (1) force decay after stepwise
      stretch of maximally Ca2+-activated fibre bundles (pCa 4.5) and (2) force decay
      from high-force rigor, the former induced by a stepwise increase in ATP
      concentration elicited by photolysis of caged ATP (pCa<8). The rate of detachment
      was not affected by thiophosphorylation or phosphorylation of twitchin by 0.12 mM
      cAMP in the presence of the phosphatase inhibitor cyclosporine A (1 microM).
      Conversely, measurements of the rate of stretch-induced delayed force increase
      (stretch activation) and of the force increase following an ATP step in low-force
      rigor (pCa 4.5) suggest that the rate of myosin head attachment decreases after
      twitchin phosphorylation. We conclude that catch is not due to myosin heads
      remaining attached to actin filaments, but depends on myofilament
      interconnections that break down when twitchin is phosphorylated.

PMID- 15952035
TI  - TRPM2: a calcium influx pathway regulated by oxidative stress and the novel
      second messenger ADP-ribose.
AB  - A unique functional property within the transient receptor potential (TRP) family
      of cation channels is the gating of TRP (melastatin) 2 (TRPM2) channels by ADP
      ribose (ADPR). ADPR binds to the intracellular C-terminal tail of TRPM2, a domain
      that shows homology to enzymes with pyrophosphatase activity. Cytosolic Ca(2+)
      enhances TRPM2 gating by ADPR; ADPR and Ca(2+) in concert may be an important
      messenger system mediating Ca(2+) influx. Other stimuli of TRPM2 include NAD and
      H(2)O(2) and cyclic ADPR, which may act synergistically with ADPR. H(2)O(2), an
      experimental paradigm of oxidative stress, may also induce the formation of ADPR
      in the nucleus or mitochondria. In this review, we summarize the gating
      properties of TRPM2 and the proposed pathways of channel activation in vivo.
      TRPM2 is likely to be a key player in several signalling pathways, mediating cell
      death in response to oxidative stress or in reperfusion injury. Moreover, it
      plays a decisive role in experimentally induced diabetes mellitus and in the
      activation of leukocytes.

PMID- 15952036
TI  - Asymmetrical distribution of ion channels in canine and human left-ventricular
      wall: epicardium versus midmyocardium.
AB  - The aim of the present study was to compare the distribution of ion currents and
      the major underlying ion channel proteins in canine and human subepicardial (EPI)
      and midmyocardial (MID) left-ventricular muscle. Ion currents and action
      potentials were recorded from canine cardiomyocytes derived from the very
      superficial EPI and central MID regions of the left ventricle. Amplitude,
      duration and the maximum velocity of depolarization of the action potential were
      significantly greater in MID than EPI myocytes, whereas phase-1 repolarization
      was more pronounced in the EPI cells. Amplitudes of the transient outwards K+
      current (29.5+/-1.5 vs. 19.0+/-2.3 pA/pF at +50 mV) and the slow component of the
      delayed rectifier K+ current (10.3+/-2.3 vs. 6.5+/-1.0 pA/pF at +50 mV) were
      significantly larger in EPI than in MID myocytes under whole-cell voltage-clamp
      conditions. The densities of the inwards rectifier K+ current, rapid delayed
      rectifier K+ current and L-type Ca2+ current were similar in both cell types.
      Expression of channel proteins in both canine and human ventricular myocardium
      was determined by Western blotting. In the canine heart, the expression of Kv4.3,
      Kv1.4, KChIP2 and KvLQT1 was significantly higher, and that of Nav1.5 and MinK
      much lower, in EPI than in MID. No significant EPI-MID differences were observed
      in the expression of the other channel proteins studied (Kir2.1, alpha1C, HERG
      and MiRP1). Similar results were obtained in human hearts, although the HERG was
      more abundant in the EPI than in the MID layer. In the canine heart, the EPI-MID
      differences in ion current densities were proportional to differences in channel
      protein expression. Except for the density of HERG, the pattern of EPI-MID
      distribution of ion-channel proteins was identical in canine and human
      ventricles.

PMID- 15952037
TI  - TRPV channels as thermosensory receptors in epithelial cells.
AB  - Temperature-sensitive transient receptor potential vanilloid (TRPV) ion channels
      are critical contributors to normal pain and temperature sensation and therefore
      represent attractive targets for pain therapy. When these channels were first
      discovered, most attention was focused on their potential contributions to direct
      thermal activation of peripheral sensory neurons. However, recent anatomical,
      physiological, and behavioral studies have provided evidence that TRPV channels
      expressed in skin epithelial cells may also contribute to thermosensation in
      vitro and in vivo. Here, we review these studies and speculate on possible
      communication mechanisms from cutaneous epithelial cells to sensory neurons.

PMID- 15952039
TI  - Do larvae of Trichobilharzia szidati and Echinostoma revolutum generate
      behavioral fever in Lymnaea stagnalis individuals?
AB  - The objective of this study was to determine whether individuals of Lymnaea
      stagnalis naturally parasitized with Trichobilharzia szidati and Echinostoma
      revolutum can generate the behavioral fever against larvae of those parasites.
      Thermal preferences of each snail were examined in an oblong thermal gradient
      during 48 h observation. Uninfected animals under study chose higher temperatures
      than those releasing cercariae of parasites. Infected snails kept in constant
      temperature lived shorter than uninfected ones. At high temperature, they
      released more cercariae per day than at low temperature. Temperature had a great
      influence on the longevity of emerged cercariae. The thermal behavior of infected
      snails is not a symptom of behavioral fever but probably can play a therapeutic
      role in the host.

PMID- 15952038
TI  - Drosophila TRP channels.
AB  - The transient receptor potential (TRP) superfamily comprises a large group of
      related cation channels that display surprising diversity in the specific modes
      of activation and cation selectivities. However, a unifying theme is that many
      TRP channels play important roles in sensory physiology. The superfamily includes
      28 mammalian members, which are subdivided into multiple subfamilies. Each of
      these subfamilies is represented by at least one of the 13 members in Drosophila,
      suggesting common evolutionary relationships. In recent years it has become clear
      that TRP channels in flies and mammals participate in similar sensory modalities.
      These include, but are not limited to, hearing, thermosensation, and certain
      specialized types of vision. With the recent flurry of new studies, 9 out of the
      13 TRPs have been addressed in various contexts. As a result, the repertoire of
      biological roles attributed to Drosophila TRPs has increased considerably and is
      likely to lead to many additional surprises over the next few years.

PMID- 15952040
TI  - Molecular characterization of Cryptosporidium species and genotypes in Chile.
AB  - Knowledge of species and genotypes on Cryptosporidium involved in human
      transmission is fundamental in studying the epidemiology of cryptosporidiosis.
      This is the first study in molecular epidemiology of cryptosporidiosis that has
      been made in Chile. Cryptosporidium parvum species and genotypes involved in
      human and bovine cryptosporidiosis were determined by PCR-RFLP. Low prevalence of
      Cryptosporidium was found in humans and cattle. Of the 127 cattle studied, only
      in one was C. parvum detected . Of the 68 human fecal samples studied, four
      contained Cryptosporidium: two patients presented Cryptosporidium hominis and two
      C. parvum. Our results confirm that anthroponotic transmission is as common as
      zoonotic in Chile. These data can enable the establishment of the corresponding
      prevention and treatment measures.

PMID- 15952041
TI  - Extracellular calcium deficiency and ryanodine inhibit Eimeria tenella sporozoite
      invasion in vitro.
AB  - An in vitro assay system with Eimeria tenella sporozoites was used to study the
      effects of extracellular calcium and active agents affecting the invasion of
      parasites into host cells. At concentrations of 900 microM Ca(2+) and less the
      invasion rates were distinctly decreased. Ryanodine, a herbal alkaloid known for
      binding to internal Ca(2+) channels (ryanodine receptors), showed an inhibitory
      effect on E. tenella sporozoite invasion. Preincubation tests and staining with a
      fluorescent derivative of ryanodine assured that the compound bound specifically
      to the sporozoites and affected them rather than the host cells.

PMID- 15952042
TI  - Cloning and characterization of a novel immunogenic protein 3 (NIP3) from Brugia
      malayi by immuno screening of a phage-display cDNA expression library.
AB  - Iterative screening of a phage display cDNA expression library of the third-stage
      larvae (L3) of Brugia malayi with sera from putatively immune individuals
      (endemic normal, EN) identified a novel clone with insert showing significant
      homology to Onchocerca volvulus novel immunogenic protein-3 (Ov-NIP3) gene and
      Caenorhabditis elegans NIP3-like protein and hence the gene was designated Brugia
      malayi NIP3-like protein (BmNIP3). EST database analysis showed that ESTs from
      several gastrointestinal nematodes such as Ancylostoma caninum, Teladorsagia
      circumcincta, Haemonchus contortus and Strongyloides stercoralis has BmNIP3
      homologues, but the gene has not been described from these parasites. Sequence
      analyses showed that BmNIP3 has three potential mucin-type O-glycosylation sites
      and several serine/threonine phosphorylation sites. As expected, BmNIP3 protein
      isolated from the parasite was serine/threonine phosphorylated. Further analyses
      showed that BmNIP3 is differentially transcribed, with highest level of
      expression present in the larval (L3 and L4) stages. Mice immunized with rBmNIP3
      developed strong antibody responses predominantly of the IgG1 and IgG2a subtype.
      A similar analyses of the sera samples from EN individuals showed that they also
      carry high levels of IgG1 and IgG2 antibodies against BmNIP3, whereas,
      chronically infected patients carry largely IgG3 antibodies and MF individuals
      carry high levels of IgG1 antibodies against BmNIP3. This study thus describes a
      novel protein from B. malayi that appears to be highly immunogenic in both humans
      and mice.

PMID- 15952043
TI  - Characterization of specific and cross-reacting antigens of Fasciola gigantica by
      immunoblotting.
AB  - Somatic antigens of F. gigantica, G. explanatum, S. spindale and hydatid cyst
      ingredients were analysed to identify the cross-reactive antigens among them
      using Western blot technique. When probed with F. gigantica infected cattle sera,
      the immunodominant 156 kDa and 28 kDa proteins of F. gigantica was found common
      amongst the antigens prepared from hydatid cysts ingredients like germinal layer,
      fertile and sterile, hydatid fluid, fertile and sterile, while another protein of
      34 kDa was shared between F. gigantica and antigen prepared from protoscolices.
      In F. gigantica-buffalo system the proteins of 34 kDa and 28 kDa were found
      reactive with most of the antigens tested. Immunoaffinity chromatography using,
      F. gigantica infected rabbit immunoglobulins as legands isolated the
      immunodominant 34 kDa and 28 kDa proteins in dimer form and the same were found
      immunodominant in F. gigantica-cattle, F. gigantica-buffalo and F. gigantica
      sheep system. No cross-reaction was noted with the sera of goats experimentally
      infected with Paramphistomum epiclitum. ELISA with the immunodominant proteins of
      34 kDa and 28 kDa could be a feasible diagnostic tool for the early detection of
      bovine fasciolosis.

PMID- 15952044
TI  - Two new species of Eimeria Schneider 1875 (Apicomplexa: Eimeriidae) from the
      broad-toothed field mouse, Apodemus mystacinus Danford and Alston 1877 (Rodentia:
      Muridae) from Jordan.
AB  - Coprological examination of 40 Apodemus mystacinus Danford and Alston 1877 from
      Jordan revealed oocysts of three species of genus Eimeria. Two species are
      described as new. Eimeria zuhairamri sp. n. has broadly ellipsoidal oocysts 29.6
      (27.0-34.0) x 23.3 (22.0-25.0) mum with distinctly granulated wall and oocyst
      residuum. Endogenous development occurs in jejunum and ileum. Eimeria alorani sp.
      n. has oocysts 26.9 (23.0-29.0) x 19.3 (18.0-22.0) mum with smooth wall and
      absent residuum. Endogenous development is confined to the caecum. The third
      species, developing in jejunum, has oocysts morphologically indistinguishable
      from Eimeria uptoni. The identity of E. uptoni and the taxonomy of Eimeria of
      Apodemus are discussed.

PMID- 15952045
TI  - Recurrent glomus tumor of the sellar region with malignant progression.

PMID- 15952048
TI  - Characterization of vestibular dysfunction in the mouse model for Usher syndrome
      1F.
AB  - The deaf-circling Ames waltzer (av) mouse harbors a mutation in the protocadherin
      15 (Pcdh15) gene and is a model for inner ear defects associated with Usher
      syndrome type 1F. Earlier studies showed altered cochlear hair cell morphology in
      young av mice. In contrast, no structural abnormality consistent with significant
      vestibular dysfunction in young av mice was observed. Light and scanning electron
      microscopic studies showed that vestibular hair cells from presumptive null
      alleles Pcdh15(av-Tg) and Pcdh15(av-3J) are morphologically similar to vestibular
      sensory cells from control littermates, suggesting that the observed phenotype in
      these alleles might be a result of a central, rather than peripheral, defect. In
      the present study, a combination of physiologic and anatomic methods was used to
      more thoroughly investigate the source of vestibular dysfunction in Ames waltzer
      mice. Analysis of vestibular evoked potentials and angular vestibulo-ocular
      reflexes revealed a lack of physiologic response to linear and angular
      acceleratory stimuli in Pcdh15 mutant mice. Optokinetic reflex function was
      diminished but still present in the mutant animals, suggesting that the defect is
      primarily peripheral in nature. These findings indicate that the mutation in
      Pcdh15 results in either a functional abnormality in the vestibular receptor
      organs or that the defects are limited to the vestibular nerve. AM1-43 dye uptake
      has been shown to correlate with normal transduction function in hair cells. Dye
      uptake was found to be dramatically reduced in Pcdh15 mutants compared to control
      littermates, suggesting that the mutation affects hair cell function, although
      structural abnormalities consistent with significant vestibular dysfunction are
      not apparent by light and scanning electron microscopy in the vestibular
      neuroepithelia of young animals.

PMID- 15952047
TI  - Auditory-nerve rate responses are inconsistent with common hypotheses for the
      neural correlates of loudness recruitment.
AB  - A number of perceptual phenomena related to normal and impaired level coding can
      be accounted for by the degree of compression in the basilar-membrane (BM)
      magnitude response. However, the narrow dynamic ranges of auditory-nerve (AN)
      fibers complicate these arguments. Because the AN serves as an information
      bottleneck, an improved understanding of the neural coding of level may clarify
      some of the limitations of current hearing aids. Here three hypotheses for the
      neural correlate of loudness recruitment were evaluated based on AN responses
      from normal-hearing cats and from cats with a noise-induced hearing loss (NIHL).
      Auditory-nerve fiber rate-level functions for tones were analyzed to test the
      following hypotheses: Loudness recruitment results from steeper AN rate functions
      after impairment. This hypothesis was not supported; AN rate functions were not
      steeper than normal following NIHL, despite steeper estimated BM responses based
      on the AN data. Loudness is based on the total AN discharge count, and
      recruitment results from an abnormally rapid spread of excitation after
      impairment. Whereas abnormal spread of excitation can be observed, steeper growth
      of total AN rate is not seen over the range of sound levels where recruitment is
      observed in human listeners. Loudness of a narrowband stimulus is based on AN
      responses in a narrow BF region, and recruitment results from compression of the
      AN-fiber threshold distribution after impairment. This hypothesis was not
      supported because there was no evidence that impaired AN threshold distributions
      were compressed and the growth of AN activity summed across BFs near the stimulus
      frequency was shallower than normal.Overall, these results suggest that loudness
      recruitment cannot be accounted for based on summed AN rate responses and may
      depend on neural mechanisms involved in the central representation of intensity.

PMID- 15952049
TI  - Physiological mechanisms of onset adaptation and contralateral suppression of
      DPOAEs in the rat.
AB  - An investigation was undertaken to measure medial olivocochlear (MOC) reflexes in
      anesthetized rats before and after sectioning of the middle-ear muscles.
      Distortion product otoacoustic emission (DPOAE) magnitude and phase temporal
      responses were measured ipsilaterally to study MOC-mediated "DPOAE onset
      adaptation" and in the presence of a contralateral noise to study MOC-mediated
      contralateral "suppression" (terms as used by previous researchers). Distortion
      product otoacoustic emission onset adaptation and contralateral suppression had
      predictable changes in direction of magnitude and phase that were dependent on
      the input-output function. After sectioning of the middle-ear muscles (MEMs),
      DPOAE onset adaptation and contralateral suppression were greatly reduced, and
      there were little, if any, changes in phase. These "residual" changes were
      interpreted as a result of the MOC reflex. The results suggest that what appears
      to be DPOAE onset adaptation and contralateral suppression can be mediated
      primarily by MEM reflexes. When studying MOC effects on otoacoustic emissions
      (OAEs) using acoustic stimulation, it is necessary to make recordings over a span
      of stimulus levels. In addition, looking at both magnitude and phase of the OAE
      may help separate what is due to the MOC reflex from MEM reflex.

PMID- 15952050
TI  - Influence of supporting cells on neuronal degeneration after hair cell loss.
AB  - In sensorineural hearing loss, hair cell loss is often followed by loss of
      cochlear nerve fibers, which can continue for years after the insult. The degree
      and time course of neuronal loss varies, but the reasons for this variation are
      unclear. The present study addresses this issue with a quantitative analysis of
      hair cell, supporting cell, and neuronal survival in animals with long-term
      survival of up to 5.5 years from two types of drug-induced hair cell loss:
      aminoglycoside antibiotics and platinum-containing chemotherapeutics. To
      complement the analysis of the effects of organ of Corti damage on neuronal
      survival, cases of primary neuronal degeneration, via auditory nerve section, are
      also assessed. Analysis shows that (1) long-term neuronal survival is enhanced
      when supporting cells in the inner hair cell (IHC) area remain intact; (2) after
      hair cell loss, the time course of neuronal loss is slower in the apex than in
      the base; (3) primary loss of cochlear nerve fibers does not lead to secondary
      degeneration of sensory cells or supporting cells in the organ of Corti; and (4)
      after auditory nerve section, there can be a massive reinnervation of the IHC
      region, especially in the apex. Results are consistent with the idea that
      supporting cells participate in the regulation of neuronal survival and neuronal
      sprouting in the organ of Corti.

PMID- 15952051
TI  - The spontaneous-rate histogram of the auditory nerve can be explained by only two
      or three spontaneous rates and long-range dependence.
AB  - Estimates of the spontaneous discharge rate (SR) of auditory-nerve (AN) fibers
      are often based on measurements of the average rate over a long (e.g., 30 s)
      interval. These measurements are important because SR is apparently correlated
      with other AN properties, such as threshold to acoustic stimuli, shape of rate
      level function, recovery from prior stimulation, and certain anatomical
      characteristics. Furthermore, histograms of SR estimates from large numbers of
      fibers suggest that they can be divided into two (i.e., low and high) or three
      (i.e., low, medium, and high) SR classes. Yet, even "simple" statistical
      estimates, such as average rate, can behave surprisingly poorly for processes
      with long-range dependence (LRD), which has been found in the spontaneous
      activity of AN fibers. In particular, LRD greatly increases the variability of
      estimates of mean discharge rate. We investigated the implications of this effect
      of LRD for our understanding of the SRs of AN fibers. The fractional-Gaussian
      noise-driven Poisson process (fGnDP) was originally developed to model the LRD
      action-potential trains of AN fibers. Using rate estimates computed from this
      model, we were able to reproduce the shape of published histograms of SR using
      only three fixed SR values. Moreover, by using a Poisson-equivalent integrate-and
      fire (IF) model in place of the inhomogeneous Poisson process in the fGnDP model,
      we were able to reproduce SR histograms using only two fixed SR values. These
      results suggest that AN fibers may have only two or three possible values for
      their long-term average spontaneous discharge rates. In other words, all "high
      SR" neurons may actually have the same underlying SR. Furthermore, both "low-SR"
      and "medium-SR" neurons may have a single "true" SR value, or these two classes
      may have two different "true" SR values. Furthermore, the Poisson-equivalent IF
      model may prove useful in other applications involving the modeling of trains of
      action potentials.

PMID- 15952052
TI  - Electrode interaction in pediatric cochlear implant subjects.
AB  - Multielectrode cochlear implants rely on differential stimulation of the cochlear
      nerve for presenting the brain with the spectral and timing information required
      to understand speech. In implant patients, the degree of overlap among cochlear
      nerve fibers stimulated by the different electrodes constitutes the electrode
      interaction. Electrode interaction degrades the spectral resolution of the
      implant's stimulus. We sought to define electrode interaction in a cohort of
      pediatric cochlear implant subjects as a function of both stimulus intensity and
      electrode location along the array. The 27 pediatric subjects that completed the
      study were implanted with either the Clarion Hi-Focus array with or without
      positioner, the Nucleus 24 Contour array, or the Nucleus 24 Straight array. All
      but two of the patients had congenital hearing loss, and none of the patients had
      meningitis prior to the onset of deafness. The cochlear nerve response was
      measured with the electrically evoked compound action potential (ECAP). A forward
      masking protocol was used such that a probe stimulus electrode remained fixed
      while a preceding masker was moved across the array. Electrode interaction was
      estimated by measuring the unmasked probe response minus the masked probe
      response. Three probe locations and three probe intensities were examined for
      each subject. At all probe locations, electrode interaction increased as probe
      intensity increased (p < 0.05). Interaction at the basal probe was less than that
      at either the middle or apical probe locations (p < 0.05), and significant
      correlation found between probe distance from the basal end of the array and
      electrode interaction (p < 0.001). These results demonstrate that in this cohort
      of pediatric subjects, electrode interaction depended on both stimulus intensity
      and probe location. Implications of these findings on future implant array design
      and current implant fitting strategies are discussed. The impact of electrode
      interaction on implant performance is yet to be elucidated.

PMID- 15952053
TI  - Auditory training with spectrally shifted speech: implications for cochlear
      implant patient auditory rehabilitation.
AB  - After implantation, postlingually deafened cochlear implant (CI) patients must
      adapt to both spectrally reduced and spectrally shifted speech, due to the
      limited number of electrodes and the limited length of the electrode array. This
      adaptation generally occurs during the first three to six months of implant use
      and may continue for many years. To see whether moderate speech training can
      accelerate this learning process, 16 naive, normal-hearing listeners were trained
      with spectrally shifted speech via an eight-channel acoustic simulation of CI
      speech processing. Baseline vowel and consonant recognition was measured for both
      spectrally shifted and unshifted speech. Short daily training sessions were
      conducted over five consecutive days, using four different protocols. For the
      test-only protocol, no improvement was seen over the five-day period. Similarly,
      sentence training provided little benefit for vowel recognition. However, after
      five days of targeted phoneme training, subjects' recognition of spectrally
      shifted vowels significantly improved in most subjects. This improvement did not
      generalize to the spectrally unshifted vowel and consonant tokens, suggesting
      that subjects adapted to the specific spectral shift, rather than to the eight
      channel processing in general. Interestingly, significant improvement was also
      observed for the recognition of spectrally shifted consonants. The largest
      improvement was observed with targeted vowel contrast training, which did not
      include any explicit consonant training. These results suggest that targeted
      phoneme training can accelerate adaptation to spectrally shifted speech. Given
      these results with normal-hearing listeners, auditory rehabilitation tools that
      provide targeted phoneme training may be effective in improving the speech
      recognition performance of adult CI users.

PMID- 15952054
TI  - Gene 33 inhibits apoptosis of breast cancer cells and increases poly(ADP-ribose)
      polymerase expression.
AB  - The structure of the Gene 33 protein suggests that it plays a role in
      intracellular signaling and Gene 33 is induced by many mitogenic and stressful
      stimuli. Previously, we found that Gene 33 expression is significantly induced by
      retinoic acid (RA), insulin and synergistically by both in a liver-derived cell
      line. In the present study, we investigated the basal expression and regulation
      of Gene 33 in multiple human breast cancer cell lines. These cell lines expressed
      different levels of Gene 33 protein, but Gene 33 protein was not regulated by RA
      or insulin, either alone, or in combination. However, epidermal growth factor
      (EGF) induced Gene 33 expression in SK-BR-3 cells and this induction was
      inhibited by co-treatment with RA. There was a strong correlation between
      endogenous basal Gene 33 expression and doubling time. Exogenous expression of
      Gene 33 in MCF-7 cells did not affect cell cycle distribution, but inhibited
      apoptosis and specifically increased the level of Poly(ADP-ribose) Polymerase
      (PARP-1) protein. This suggests that Gene 33 promotes breast cancer cell growth
      by an anti-apoptotic rather than a mitogenic effect, possibly involving up
      regulation of PARP-1.

PMID- 15952055
TI  - Predictors of central nervous system metastasis in patients with metastatic
      breast cancer. A competing risk analysis of 579 patients treated with epirubicin
      based chemotherapy.
AB  - In order to identify factors predictive of central nervous system (CNS)
      metastasis, we reviewed the histories of 579 patients treated with epirubicin
      based chemotherapy for metastatic breast cancer. Statistical analysis included
      Kaplan-Meier survival plots, Cox's regression analysis and competing risk
      analysis using the cumulative incidence. Median follow-up-time was 137 months
      (range 0-183+). In this period, one hundred and twenty-four patients (21.4%)
      developed CNS metastasis. Lung, liver, and lymph node metastases and oestrogen
      receptor negative or unknown tumor were predictive as well. However, increased
      pretreatment lactate dehydrogenase (LDH) concentration in serum above the upper
      normal limits was the strongest single risk factor and should therefore be
      measured. The risk of CNS metastasis differed considerably among risk groups.
      Patients without risk factors had a cumulative incidence on 9%, compared to a
      cumulative incidence of 42%, when the serum LDH concentration was elevated to
      more than twice the upper normal limits.

PMID- 15952056
TI  - Galectins as markers of aggressiveness of mouse mammary carcinoma: towards a
      lectin target therapy of human breast cancer.
AB  - Galectins, beta-galactoside binding proteins, expressed selectively in human
      breast carcinoma are attractive targets to employ lectin-aimed therapeutics. We
      examined beta-galactoside binding potency of neoplastic cells using fluorescein
      labelled synthetic glycoconjugates as probes for flow cytometry. As a result,
      surface beta-galactoside binding proteins/galectins were discovered on mouse
      mammary carcinoma cells in vitro and in vivo unlike non-malignant cells from the
      several tissues; and asialo-GM1 ganglioside carbohydrate part--containing probe
      was the most specific one. However, in liver and lung metastatic cells galectins
      seem to be expressed within cytoplasm and/or nuclei. Galectin expression
      correlated directly with aggressive tumour potential in the A/Sn transplantable
      model similar to findings in several human breast carcinoma cell lines. However,
      galectin expression was reduced during tumour progression in more aggressive
      forms of spontaneous BLRB mammary carcinomas like it was shown for human breast
      carcinoma specimens. Analysis of the histopathological data led, however, to the
      conclusion that galectin expression hardly might be a suitable marker of
      aggressiveness of heterogeneous mammary carcinomas as the observed level of
      galectin expression is influenced by the amount of the stroma in a tumour sample
      and/or probably, galectin expression inversely correlates with tumour
      aggressiveness during the initial and advanced steps of mammary tumour
      progression. We conclude that surface beta-galactoside binding proteins/galectins
      that are selectively expressed during mouse mammary carcinoma progression,
      similarly to human breast carcinomas, seem to be proper targets for asialo-GM1
      vectored cytotoxics and our mouse model system might be a relevant instrument to
      further test novel modes of anti-breast cancer therapy.

PMID- 15952057
TI  - Racial disparities in treatment and survival of women with stage I-III breast
      cancer at a large academic medical center in metropolitan Detroit.
AB  - African-American (AA) women with breast cancer have higher mortality rates than
      Caucasian woman, and some studies have suggested that this disparity may be
      partly explained by unequal access to medical care. The purpose of this study was
      to analyze racial differences in patterns and costs of care and survival among
      women treated for invasive breast cancer at a large academic medical center.
      Subjects included 331 AA and 257 Caucasian women diagnosed with stage I-III
      breast cancer between 1994 and 1997. Clinical, socio-demographic, and cost data
      were obtained from the medical record, cancer registry, and hospital financial
      database. Data were collected on the use of cancer directed treatments (surgery,
      radiation, chemo and hormonal therapy) up to 1-year post-diagnosis. Survival
      analyses compared disease-free and overall survival by race adjusting for age,
      stage, nodal involvement, ER/PR status and a diagnosis of hypertension, diabetes,
      heart disease and cerebral vascular accident. There were no significant racial
      differences in treatment utilization and costs. The mean total 1-year treatment
      costs were US 16,348 dollars for AAs and US 15,120 dollars for Caucasians. While
      AAs had a significantly higher unadjusted relative risk (RR) of recurrence 2.09
      (95% CI: 1.41-3.10) and death 1.56 (95% CI: 1.09-2.25), the multivariate adjusted
      analyses resulted in no significant differences in recurrence 1.38 (95% CI: 0.85
      2.26) or death 1.06 (95% CI: 0.64-1.75). There was no obvious racial disparity in
      treatment and costs noted. Our findings support the theory that equal treatments
      produce equal outcomes. Improvement in screening may have an important impact on
      survival among minority women with breast cancer.

PMID- 15952058
TI  - Association of genetic variation in tamoxifen-metabolizing enzymes with overall
      survival and recurrence of disease in breast cancer patients.
AB  - Tamoxifen has been a mainstay of adjuvant therapy for breast cancer for many
      years. We sought to determine if genetic variability in the tamoxifen metabolic
      pathway influenced overall survival in breast cancer patients treated with
      tamoxifen. We examined functional polymorphisms in CYP2D6, the P450 catalyzing
      the formation of active tamoxifen metabolites, and UGT2B15, a Phase II enzyme
      facilitating the elimination of active metabolite in a retrospective study of
      breast cancer patients. We also examined whether the combination of variant
      alleles in SULT1A1 and UGT2B15 had more of an impact on overall survival in
      tamoxifen-treated patients than when the genes were examined separately. We
      conducted a retrospective study using archived paraffin blocks for DNA extraction
      and data from pathology reports and hospital tumor registry data for information
      on clinical characteristics, treatment, and outcomes (162 patients receiving
      tamoxifen and 175 who did not). Genotypes for CYP2D6 and UGT2B15 were obtained
      and Cox proportional hazards modeling was performed. After adjusting for age,
      race, stage of disease at diagnosis, and hormone receptor status, we found no
      significant association between CYP2D6 genotype and overall survival in either
      group of breast cancer patients. Tamoxifen-treated patients with UGT2B15 high
      activity genotypes had increased risk of recurrence and poorer survival. When
      UGT2B15 and SULT1A1 'at-risk' alleles were combined, women with two variant
      alleles had significantly greater risk of recurrence and poorer survival than
      those with common alleles. These studies indicate that genetic variation in Phase
      II conjugating enzymes can influence the efficacy of tamoxifen therapy for breast
      cancer.

PMID- 15952059
TI  - PKCdelta and mTOR interact to regulate stress and IGF-I induced IRS-1 Ser312
      phosphorylation in breast cancer cells.
AB  - IRS-1 (Insulin Receptor Substrate-1) is an adaptor protein important for insulin
      and IGF-I receptor (Insulin-like Growth Factor-IR) transduction to downstream
      targets. One mechanism recently identified to downregulate IGF-I or insulin
      receptor signaling in diabetic models is IRS-1 Ser(312) phosphorylation. To date,
      the importance of this residue in cancer is unknown. This paper identifies
      mechanisms leading to Ser(312) regulation in MCF-7 breast cancer cells. Whereas
      IGF-I phosphorylation of IRS(312) is PI (phosphatidylinositol) 3-kinase
      dependent, anisomycin stress treatment requires JNK activation to induce
      phosphorylation of IRS(312). We show that both IGF-I and anisomycin stress
      treatment converge downstream onto mTOR (Mammalian Target of Rapamycin) and
      PKCdelta (Protein Kinase C-delta) to induce IRS-1 Ser(312) phosphorylation. mTOR
      associates with IRS-1 and is primarily required for Ser(312) phosphorylation in
      response to stress or IGF-I treatment. PKCdelta binds to mTOR and its activity is
      also important for stress or IGF-I mediated Ser(312) phosphorylation. Thus, mTOR
      and PKCdelta convey diverse signals to regulate IRS-1 function.

PMID- 15952060
TI  - Tat mammaglobin fusion protein transduced dendritic cells stimulate mammaglobin
      specific CD4 and CD8 T cells.
AB  - Proteins can be efficiently introduced into cells when fused to a protein
      transduction domain, such as Tat from the human immunodeficiency virus. We
      recently reported that dendritic cells transduced with a Tat fusion protein
      containing the extracellular domain of Her2/neu (Tat-Her2/neu) induced CD8
      cytotoxic T lymphocytes (CTL) that specifically lysed Her2/neu-expressing breast
      and ovarian cancer cells. In the current study we further investigated the
      mechanism of protein transduction, utilizing the breast cancer-associated
      protein, mammaglobin-A, which is expressed in about 80% of breast cancers. Using
      a Tat-mammaglobin fusion protein, we tested the ability of Tat-mammaglobin
      transduced dendritic cells to stimulate antigen-specific CD4 and CD8 T cells. Low
      levels of serum considerably improved protein transduction as determined by
      Western blot, and also improved presentation of antigenic peptide as evidenced by
      functional studies using antigen-specific T cells. Confocal microscope analyses
      of antigen-presenting cells (APC) incubated with Tat-mammaglobin showed localized
      distribution in addition to diffuse distribution in the cytosol. In contrast,
      mammaglobin lacking Tat showed only a localized distribution. Simultaneous
      incubation with both proteins resulted in overlapping localized distributions,
      suggesting Tat fusion proteins are processed through both the MHC class I and
      class II pathways. Indeed, stimulation of T cells with Tat-mammaglobin transduced
      dendritic cells led to an expansion of mammaglobin-specific CD4 T helper-1
      lymphocytes along with CD8 CTL. We conclude that Tat-mammaglobin transduced
      dendritic cells can induce both CD4 and CD8 mammaglobin-specific T cells. These
      findings could be further exploited for the development of a mammaglobin-based
      vaccine for breast cancer.

PMID- 15952061
TI  - The benefit of participating to clinical research.
AB  - We assessed the impact of participating to clinical research among 1727 women
      with localized breast cancer. Using as referent individuals not treated according
      to guidelines for systemic therapy, the adjusted hazard ratio of death was 0.70
      (95% confidence interval (CI): 0.54,0.90, p-value: 0.006) in those treated
      according to current guidelines and 0.45 (95% CI: 0.27,0.73, p-value: 0.001) in
      participants to research. Participation to clinical trials results in a
      substantial gain in survival.

PMID- 15952065
TI  - Activation of the WUS gene induces ectopic initiation of floral meristems on
      mature stem surface in Arabidopsis thaliana.
AB  - A gain-of-function Arabidopsis mutant was identified via activation tagging
      genetic screening. The mutant exhibited clustered ectopic floral buds on the
      surface of inflorescence stems. The mutant was designated as sef for stem ectopic
      flowers. Our detailed studies indicate that the ectopic flower meristems are
      initiated from the differentiated cortex cells. Inverse PCR and sequence analysis
      indicated that the enhancer-containing T-DNA from the activation tagging
      construct, SKI015, was inserted upstream of the previously cloned WUS gene
      encoding a homeodomain protein. Studies from RT-PCR, RNA in situ hybridization
      and transgenic plant analysis further confirmed that the phenotypes of sef are
      caused by the overexpression of WUS. Our results suggest that overexpression of
      WUS could trigger the cell pluripotence and reestablish a new meristem in cortex.
      The type of new meristems caused by WUS overexpression was dependent upon the
      developmental and physiological stages of a plant. With the help of some
      undefined factors in the reproductive organs the new meristems differentiated
      into floral buds. In a vegetative growth plant, however, only the new vegetative
      buds can be initiated upon the overexpression of WUS. These studies provide new
      insights of WUS on flower development.

PMID- 15952066
TI  - New insights into the complex and coordinated transcriptional regulation networks
      underlying rice seed development through cDNA chip-based analysis.
AB  - Transcription factors (TFs) are major, crucial factors for developmental control.
      To elucidate the effects of TFs on rice seed development, we generated a cDNA
      chip containing 325 rice cDNA clones, which are from flowering stage and encode
      known or putative TFs belonging to 12 different families, and used this chip for
      expression profiling at 8 continuous seed developmental stages. The results
      showed that in comparison to their expression in mature leaves, a total of 135 TF
      genes were preferentially transcribed in seeds. Cluster analysis based on the
      temporal expression patterns grouped them into 12 types, each of which contained
      members of various families showing common unique expression patterns. The
      results provide insights into possible key roles for members of several TF
      families during seed development. In addition, the expression patterns of these
      genes were examined in vegetative tissues including roots, seedlings and stems,
      as well as in 2-week-old seedlings following the application of plant hormones or
      abiotic stresses. The results showed that many of the seed-preferential TFs were
      also involved in hormone and/or abiotic stress effects, suggesting the potential
      existence of uncharacterized transcriptional networks, or cross talk between
      hormone and abiotic stress signaling and seed development. Furthermore, analysis
      on the cis-elements locating in promoter region of seed preferential TF genes
      suggested that Dof proteins play essential roles in hierarchical regulation of
      gene expressions during rice seed development, which, taken together, provided
      informative clues for elucidation of the molecular mechanisms of transcriptional
      regulation and signaling networks in the complex developmental processes of rice
      seeds.

PMID- 15952067
TI  - Differential regulation of chlorophyll a oxygenase genes in rice.
AB  - Chlorophyll b is synthesized from chlorophyll a by chlorophyll a oxygenase. We
      have identified two genes (OsCAO1 and OsCAO2) from the rice genome that are
      highly homologous to previously studied chlorophyll a oxygenase (CAO) genes. They
      are positioned in tandem, probably resulting from recent gene duplications. The
      proteins they encode contain two conserved functional motifs - the Rieske Fe
      sulfur coordinating center and a non-heme mononuclear Fe-binding site. OsCAO1 is
      induced by light and is preferentially expressed in photosynthetic tissues. Its
      mRNA level decreases when plants are grown in the dark. In contrast, OsCAO2 mRNA
      levels are higher under dark conditions, and its expression is down-regulated by
      exposure to light. To elucidate the physiological function of the CAO genes, we
      have isolated knockout mutant lines tagged by T-DNA or Tos17. Mutant plants
      containing a T-DNA insertion in the first intron of the OsCAO1 gene have pale
      green leaves, indicating chlorophyll b deficiency. We have also isolated a pale
      green mutant with a Tos17 insertion in that OsCAO1 gene. In contrast, OsCAO2
      knockout mutant leaves do not differ significantly from the wild type. These
      results suggest that OsCAO1 plays a major role in chlorophyll b biosynthesis, and
      that OsCAO2 may function in the dark.

PMID- 15952068
TI  - Arabidopsis Rad51B is important for double-strand DNA breaks repair in somatic
      cells.
AB  - Rad51 paralogs belong to the Rad52 epistasis group of proteins and are involved
      in homologous recombination (HR), especially the assembly and stabilization of
      Rad51, which is a homolog of RecA in eukaryotes. We previously cloned and
      characterized two RAD51 paralogous genes in Arabidopsis, named AtRAD51C and
      AtXRCC3, which are considered the counterparts of human RAD51C and XRCC3,
      respectively. Here we describe the identification of RAD51B homologue in
      Arabidopsis, AtRAD51B. We found a higher expression of AtRAD51B in flower buds
      and roots. Expression of AtRAD51B was induced by genotoxic stresses such as
      ionizing irradiation and treatment with a cross-linking reagent, cisplatin. Yeast
      two-hybrid analysis showed that AtRad51B interacted with AtRad51C. We also found
      and characterized T-DNA insertion mutant lines. The mutant lines were devoid of
      AtRAD51B expression, viable and fertile. The mutants were moderately sensitive to
      gamma-ray and hypersensitive to cisplatin. Our results suggest that AtRAD51B gene
      product is involved in the repair of double-strand DNA breaks (DSBs) via HR.

PMID- 15952069
TI  - The Oryza sativa no pollen (Osnop) gene plays a role in male gametophyte
      development and most likely encodes a C2-GRAM domain-containing protein.
AB  - Phenotype screens of Ds insertional lines identified a male sterile Orysa sativa
      no pollen (Osnop) mutant with a pollen-less phenotype at the flowering stage. The
      mutant phenotype showed linkage to Ds insertion into Osnop gene region. This
      mutant contained a deletion of 65 kb chromosomal region at the site of Ds
      insertion containing 14 predicted genes. Out of these deleted genes, Delegen 5-7,
      9-10 were redundant, as two or three copies were present with 100% homology in
      other regions of rice genome. RT-PCR analysis showed that Delegen 5-7 were
      expressed not only in wild type plants but also in the mutant plants. In addition
      to this, Delegen 8-10 transcripts could not be detected under normal growth
      conditions, and Delegen 12 was expressed only in roots, thus deletion of these
      genes may not affect the pollen development. Our data and analysis also ruled out
      the possibility of delegen 1-4, 11, and 13 as candidates contributing to the
      pollen-less phenotype. Further investigation showed that the delegen 14 was
      expressed only in late stage of pollen development with the highest expression at
      the stage of pollen release and germination by RT-PCR, Northern blotting, in situ
      hybridization, and promoter-GUS transgenic plants. Thus, the delegen 14 gene is
      the best candidate for Osnop, corresponding to the pollen-less phenotype in the
      mutant. Our data suggest that delegen 14 may play an important role during late
      stage of pollen development and its germination. Since the delegen 14 gene has
      both C(2) and GRAM domains, it can be assumed that this gene cross-links both
      calcium and phosphoinositide signaling pathways. This is the first report to
      suggest possible functions for this gene in plant development.

PMID- 15952070
TI  - CaaX-prenyltransferases are essential for expression of genes involvedin the
      early stages of monoterpenoid biosynthetic pathway in Catharanthus roseus cells.
AB  - CaaX-prenyltransferases (CaaX-PTases) catalyse the covalent attachment of
      isoprenyl groups to conserved cysteine residues located at the C-terminal CaaX
      motif of a protein substrate. This post-translational modification is required
      for the function and/or subcellular localization of some transcription factors
      and components of signal transduction and membrane trafficking machinery. CaaX
      PTases, including protein farnesyltransferase (PFT) and type-I protein
      geranylgeranyltransferase (PGGT-I), are heterodimeric enzymes composed of a
      common alpha subunit and a specific beta subunit. We have established RNA
      interference cell lines targeting the beta subunits of PFT and PGGT-I,
      respectively, in the Catharanthus roseus C20D cell line, which synthesizes
      monoterpenoid indole alkaloids in response to auxin depletion from the culture
      medium. In both types of RNAi cell lines, expression of a subset of genes
      involved in the early stage of monoterpenoid biosynthetic pathway (ESMB genes),
      including the MEP pathway, is strongly decreased. The role of CaaX-PTases in ESMB
      gene regulation was confirmed by using the general prenyltransferase inhibitor s
      perillyl alcohol (SP) and the specific PFT inhibitor Manumycin A on the wild type
      line. Furthermore, supplementation of SP inhibited cells with monoterpenoid
      intermediates downstream of the steps encoded by the ESMB genes restores
      monoterpenoid indole alkaloids biosynthesis. We conclude that protein targets for
      both PFT and PGGT-I are required for the expression of ESMB genes and
      monoterpenoid biosynthesis in C. roseus, this represents a non previously
      described role for protein prenyltransferase in plants.

PMID- 15952071
TI  - A reporter gene system used to study developmental expression of alternative
      oxidase and isolate mitochondrial retrograde regulation mutants in Arabidopsis.
AB  - Perturbation of mitochondrial function causes altered nuclear gene expression in
      plants. To study this response, called mitochondrial retrograde regulation, and
      developmental gene expression, a transgenic Arabidopsis thaliana (Col-0) line
      containing a firefly luciferase gene controlled by a promoter region of the
      Arabidopsis alternative oxidase 1a gene (AtAOX1a) was created. The transgene and
      the endogenous gene were developmentally induced in young cotyledons to a level
      higher than in older cotyledons and leaves. Analysis of transgene expression
      suggests that this is true for emerging leaves as well. Antimycin A (AA), a
      mitochondrial electron transport chain inhibitor, and monofluroacetate (MFA), a
      TCA cycle inhibitor, induced expression of the transgene and the endogenous gene
      in parallel. The following comparative responses of the transgene to inhibitors
      were observed: (a) the response in cotyledons to AA treatment differed greatly in
      magnitude from the response in leaves; (b) the induction kinetics in cotyledons
      following MFA treatment differed greatly from the kinetics in leaves; and (c) the
      induction kinetics following MFA treatment differed from the kinetics of AA in
      both leaves and cotyledons. The transgenic line was used in a genetic screen to
      isolate mutants with greatly decreased transgene and AtAOX1a induction in
      response to AA. Some of these mutant lines showed greatly decreased induction by
      MFA, but one did not. Taken altogether, the data provide genetic evidence that
      suggests that induction of the AtAOX1a gene by distinct mitochondrial
      perturbations are via distinct, but overlapping signaling pathways that are
      tissue specific.

PMID- 15952072
TI  - Identification of novel clock-controlled genes by cDNA macroarray analysis in
      Chlamydomonas reinhardtii.
AB  - Circadian rhythms are self-sustaining oscillations whose period length under
      constant conditions is about 24 h. Circadian rhythms are widespread and involve
      functions as diverse as human sleep-wake cycles and cyanobacterial nitrogen
      fixation. In spite of a long research history, knowledge about clock-controlled
      genes is limited in Chlamydomonas reinhardtii. Using a cDNA macroarray containing
      10 368 nuclear-encoded genes, we examined global circadian regulation of
      transcription in Chlamydomonas. We identified 269 candidates for circadianly
      expressed gene. Northern blot analysis confirmed reproducible and sustainable
      rhythmicity for 12 genes. Most genes exhibited peak expression at the transition
      point between day and night. One hundred and eighteen genes were assigned
      predicted annotations. The functions of the cycling genes were diverse and
      included photosynthesis, respiration, cellular structure, and various metabolic
      pathways. Surprisingly, 18 genes encoding chloroplast ribosomal proteins showed a
      coordinated circadian pattern of expression and peaked just at the beginning of
      subjective day. The co-regulation of genes bearing a similar function was also
      observed in genes involved in cellular structure. They peaked at the end of the
      subjective night, which is when the regeneration of cell walls and flagella in
      daughter cells occurs. Expression of the chlamyopsin gene, which encodes an opsin
      type photoreceptor, also exhibited circadian rhythm.

PMID- 15952075
TI  - Predicting the presence of parathyroid carcinoma.

PMID- 15952073
TI  - Intragenic diversity and functional conservation of the three homoeologous loci
      of the KN1-type homeobox gene Wknox1 in common wheat.
AB  - Common wheat represents a typical allohexaploid species and provides a good
      experimental system for studying genomic alterations associated with
      allopolyploidization. We studied three homoeologous loci of wheat Wknox1 gene,
      which is highly homologous to the knotted1 (kn1)-like homeobox (KNOX) genes
      functioning at shoot apical meristems (SAM). Wknox1 transcripts were detected in
      SAM, and its overexpression caused abnormal leaf morphology with occasional
      ectopic leaves in transgenic tobacco plants. A comparative study of the three
      Wknox1 genomic sequences revealed accumulation of a large number of mutations
      including insertions and deletions, particularly in the fourth intron and the 5'
      upstream region. Some structural mutations including MITE-insertions were
      allocated in the evolutionary lineage of the wheat genome, suggesting that they
      occurred at all stages of wheat evolution. A mutation rate was the highest in the
      Wknox1b locus, which is consistent with the known highest degree of
      differentiation in the B genome. Despite the structural differentiation, all
      three Wknox1 homoeologs showed an identical expression pattern in wheat and their
      promoter regions induced the conserved expression pattern in transgenic tobacco
      plants. A potential of the intragenic diversity in homoeologs of essential genes
      as a tool for studying the genome evolution associated with allopolyploidization
      was discussed.

PMID- 15952076
TI  - Obesity and cortisol status.
AB  - The fact, that obesity is a prominent feature of hypercortisolism (Cushing's
      syndrome) has stimulated investigation on the possible existence of the reverse
      relationship, namely that hypercortisolism is a feature of obesity. We have
      reviewed half a century of literature on this question, and have found out the
      following: (1) Hypercortisolism can exist in two forms: systemic
      hypercortisolism, in which there is an overall bodily excess of cortisol, and
      tissue, or intracellular, hypercortisolism, in which there is increased
      intracellular concentration of cortisol without an overall bodily excess. (2)
      There are two parameters of systemic hypercortisolism: CPR and plasma cortisol
      concentration. Proper evaluation of the first parameter requires correction for
      the active metabolic mass, which is best performed by expressing CPR per gram of
      urinary creatinine. The second parameter can be confounded by the marked moment
      to-moment fluctuations in plasma cortisol concentrations due to cortisol's
      episodic secretion. Proper evaluation requires measuring the 24-hour mean
      concentration. Of these two parameters of systemic cortisol status, the plasma
      concentration is the more critical and accurate. (3) Corrected CPR is normal in
      obese individuals, and 24-hour mean plasma cortisol concentrations are slightly
      but definitely subnormal. This combination of findings indicates diminished
      stimulability of the hypothalamic-pituitary-adrenal (HPA) axis, which normally
      regulates bodily cortisol status. This deduction is supported by empirical
      studies on HPA reactivity. (4) Tissue hypercortisolism, due to increased
      intracellular activity of 11beta-HSD-1, which catalyzes reduction of cortisone to
      cortisol, has been reported in obese mice and humans. The findings of various
      studies are not consistent, and whether the enzymatic overactivity is a cause or
      a result of obesity is still unclear.

PMID- 15952077
TI  - Isoproterenol opens K+(ATP) channels via a beta2-adrenoceptor-linked mechanism in
      Sertoli cells from immature rats.
AB  - In the present study, we investigated the mechanism by which isoproterenol
      hyperpolarises membrane potential (MP) in Sertoli cells from seminiferous tubules
      of 15-day-old rat testes. Modification of MP and resistance (R0) was analysed
      using conventional intracellular glass microelectrodes. Isoproterenol (2 x 10(-6)
      M) induced an immediate and significant hyperpolarisation in the Sertoli-cell
      membrane. The beta2-AR antagonist, butoxamine (1 x 10(-6) M), nullified
      isoproterenol action. The effect of the beta1 antagonist, metoprolol (1 x 10(-6)
      M), was light and non-significant. Sulphonylurea glibenclamide inhibition of the
      K+(ATP) channels suppressed isoproterenol action, and testosterone, while
      depolarising Sertoli-cell MP closing the K+(ATP) channels through the PLC/PIP2
      pathway, reduced beta-AR agonist-induced hyperpolarisation. Also, polycations
      LaCl3 and spermine reversed isoproterenol's hyperpolarisation effect, probably
      depolarising the membrane potential through ionic interaction neutralising the
      action of isoproterenol on K+(ATP) channels. Adenylate cyclase agonist forskolin
      (0.1 microM) rapidly hyperpolarised Sertoli-cell MP, mimicking the isoproterenol
      effect. These effects indicate that isoproterenol's action on K+(ATP) channel
      probably involves the known signalling cascade beta-AR/Gs/AC/cAMP/PKA. These
      results suggest that the isoproterenol-induced hyperpolarisation is mediated by
      the opening of K+(ATP) channels in Sertoli cells. This beta-adrenergic
      hyperpolarisation might play a physiological role in the modulation of MP.

PMID- 15952078
TI  - Glucagon does not affect catecholamine release in primary cultures of bovine
      adrenal chromaffin cells.
AB  - OBJECTIVE: Human pheochromocytoma tumor cells express glucagon receptors, and
      bolus i.v. glucagon injection rapidly increases plasma epinephrine levels,
      suggesting that glucagon can directly stimulate adrenomedullary secretion. In
      this study, we tested whether the catecholamine secretory response to glucagon
      was present in bovine chromaffin cells or exclusive to the tumor cells. DESIGN
      AND METHODS: Adrenomedullary cells were cultured in 24-well plates (10(6) cells
      per well). After 48-72 hours, wells were incubated for 1-20 minutes with (1)
      incubation medium (control), (2) catecholamine secretagogues (nicotine or
      potassium ion), or (3) glucagon (10(-8) to 10(-5) M). After incubation,
      catecholamine contents in medium and cells were assayed by high-pressure liquid
      chromatography with electrochemical detection. Fractional release rates of
      epinephrine, norepinephrine, and dopamine were calculated and compared to
      controls. Reverse-transcriptase PCR was performed to compare expression of mRNA
      of the glucagon receptor in chromaffin cells and pheochromocytoma cells. RESULTS:
      Nicotine and potassium evoked time-dependent release of epinephrine,
      norepinephrine, and dopamine. Glucagon did not affect catecholamine secretion at
      any concentration. Reverse-transcriptase PCR failed to detect mRNA for glucagon
      receptor in bovine adrenomedullary cells, but did detect it in human
      pheochromocytoma cells. CONCLUSIONS: In contrast to pheochromocytoma tumor cells,
      bovine adrenomedullary chromaffin cells do not express the glucagon receptor, and
      therefore do not secrete catecholamines in response to glucagon.

PMID- 15952079
TI  - Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia
      during GABA(A) receptor inhibition.
AB  - We performed this study to determine whether gamma-aminobutyric acid (GABA(A))
      receptor inhibition could reverse the effect of 17beta-estradiol on blood-brain
      barrier (BBB) disruption in focal cerebral ischemia. Young ovariectomized rats
      were implanted with a 500 microg 17beta-estradiol 21-day release pellet or with a
      vehicle pellet 21 days before the experiments. Forty-five minutes after middle
      cerebral artery (MCA) occlusion, half of each group was infused with bicuculline
      (a GABA(A) receptor antagonist) 1 mg/kg/min for 2 min followed by 0.1 mg/kg/min
      up to the end of experiments. The other half was infused with the same volume of
      normal saline. The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid
      and the volume of 3H-dextran distribution (70,000 Daltons) were determined to
      measure the degree of BBB disruption one hour after MCA occlusion. In the control
      vehicle-treated animals, the Ki in the ischemic cortex (7.2 +/- 2.6 microl/g/min)
      was higher than in the contralateral cortex (2.5 +/- 1.4 microl/g/min). After
      bicuculline infusion, the Ki in the ischemic cortex increased (10.6 +/- 5.4
      microl/g/min) although the increase was not statistically significant. In the
      17beta-estradiol treated animals, the Ki in the ischemic cortex (3.8 +/- 1.6
      microl/g/min) was lower than control vehicle-treated rats. With bicuculline
      infusion, the Ki in the ischemic cortex (14.5 +/- 6.8 microl/g/min) was markedly
      increased. In the non-ischemic cortex, there was no significant difference in Ki
      among the experimental groups. The volume of dextran distribution was not
      significantly different between the experimental groups in the ischemic or non
      ischemic cortex. Our data suggests that part of the reason for the decreased BBB
      disruption in the focal ischemic area after 17beta-estradiol treatment could be
      due to the interaction between GABA(A) receptors and 17beta-estradiol.

PMID- 15952080
TI  - Effects of different culture conditions and leptin on GH mRNA expression and GH
      secretion by pig pituitary cells.
AB  - Growth hormone (GH) is enhanced in malnutrition; physiological increments in GH
      secretion seem to play an important role in regulating metabolism during fasting.
      Leptin has also been shown to play a role, amongst others, in modulating the
      somatotropic axis. In this study, we investigated how the composition of culture
      media could influence basal and leptin-stimulated GH secretion and expression in
      pig pituitary cells. Pituitary cells from 8-month-old sows were incubated for 48
      h in presence and absence of 10% fetal calf serum, either in DMEM/Ham's F12, in
      arginine-free DMEM/Ham's F-12, or in DMEM/Ham's F12 Salts. Cells were then
      treated for 24 h with GHRH or recombinant human leptin (rhLep) individually or in
      association with GHRH; cell proliferation, nitric oxide (NO) production and GH
      expression and secretion were determined. The absence of nutritional factors
      induced a decrease in cell proliferation, but stimulated both GH secretion and
      expression. Furthermore, rhLep significantly increased GH expression and
      secretion irrespective of culture conditions. NO production was only
      significantly enhanced by leptin under DMEM/Ham's F12 culture conditions. These
      observations lead us to hypothesize that the adaptive capabilities of pituitary
      cells may overcome the negative effects of undernutrition; in this context,
      leptin does not seem to depend on NO pathways in modulating GH secretion.

PMID- 15952081
TI  - Prolactin inhibition in lactating rats changes leptin transfer through the milk.
AB  - Malnutrition during lactation reduces milk production and changes pup's leptin
      serum levels. To test prolactin role in this nutritional state, we evaluated
      whether prolactin suppression during lactation changes serum leptin in dams, its
      transfer through the milk, and pup's serum leptin. Lactating rats were treated
      with bromocryptine (1 mg/twice a day, s.c.) or saline three days before sacrifice
      (days 2-4 or days 19-21). Food intake and body weight were measured until
      sacrifice (4th and 21st day). Serum prolactin and leptin were determined by
      radioimmunoassay. Bromocryptine injected dams had lower serum prolactin and milk
      production as expected. The mothers presented lower food ingestion (day 21: 
      25%), lower body weight (day 4: -12%; day 21: -10%), higher serum leptin (day 4:
      +68%), lower milk leptin on the 4th day (11 times) and higher (8 times) on the
      21st day. The offspring of bromocryptine-treated mothers presented lower body
      weight in both periods of lactation and lower serum leptin on the 4th day (-40%)
      and higher on the 21st day (+37%) of lactation. We suggest that prolactin,
      through its effect on leptin secretion into the milk, may play an important role
      in signalizing maternal nutritional status to the pups.

PMID- 15952082
TI  - Effect of hormone replacement therapy on the production of bone-resorbing
      cytokines by peripheral blood cells in postmenopausal women.
AB  - We studied the effects of hormone replacement therapy (HRT) with estrogen on
      postmenopausal changes in the production of bone-resorbing cytokines interleukin
      1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha). Both cytokines were
      measured in the supernatants of lipopolysaccharide (LPS)-stimulated whole-blood
      cells from 72 untreated and 44 HRT-treated women by ELISA. The levels of IL-1beta
      were significantly higher in women in their 40s and 50s and in postmenopausal
      women than in women in their teens, 20s and 30s, while the levels of TNFalpha did
      not show any changes related to age. Both levels in HRT-treated women were
      significantly lower than those in untreated women at almost every postmenopausal
      stage. In a prospective study, HRT induced significant declines in both levels.
      These results show that estrogen decreases the accelerated production of IL-1beta
      and reduces the production of TNFalpha in postmenopausal women at each
      postmenopausal stage, even in late-postmenopausal women.

PMID- 15952083
TI  - Inheritance of R337H p53 gene mutation in children with sporadic adrenocortical
      tumor.
AB  - Adrenocortical tumors (ACTs) are frequent in Brazil. The mechanisms of adrenal
      tumorigenesis remain poorly established; the R337H germline mutation in the p53
      gene has previously been associated with ACTs in Brazilian children. We
      investigated the frequency and inheritance of R337H p53 mutation as well as
      genotype and phenotype correlation in 21 children and 5 adult patients with ACTs.
      DNA was extracted from peripheral blood cells and/or tumor tissue for sequencing
      exon 10 of the p53 gene. Nine sets of parents of patients with p53 mutation were
      also submitted to mutational analysis. Virilization was the most common clinical
      sign in children with or without Cushing's syndrome. Two members of the adult
      group showed asymptomatic adrenal incidentalomas, two showed virilization, and
      one presented with Cushing's syndrome. Sixteen children with ACTs had peripheral
      blood available, and twelve of them (75%) showed the heterozygous R337H p53 gene
      mutation. The R337H mutation was found in fifteen samples of the nineteen tumor
      specimens available (78.9%). Among the nine sets of parents of the patients with
      R337H mutation, eight showed the same mutation with heterozygosity in one of the
      parents. None of the parents showed ACTs or any other neoplasia at the time of
      the study. Only one adult patient with an ACT revealed the same R337H p53
      germline mutation. There was no association between the presence of germline or
      tissue R337H p53 mutation and malignancy at diagnosis. We confirmed the high
      frequency of R337H p53 mutation in Brazilian children with sporadic ACTs. The
      R337H p53 mutation was inherited from one of the parents of the patients, and
      there was no association between the presence of this mutation and tumor
      malignancy in children. The founder effect of R337H p53 mutation and the role of
      environmental mutagens contributing to the geographical clustering and high
      prevalence of ACTs in Brazilian children remain to be established.

PMID- 15952084
TI  - Differences in infantile growth patterns in Turner syndrome girls with and
      without spontaneous puberty.
AB  - OBJECTIVE: The role of prepubertal estrogen in child growth was modeled using
      Turner's syndrome, comparing growth patterns of girls who later did or did not
      enter puberty spontaneously. The hypothesis was that TS patients with normal
      prepubertal estrogen levels would have a different growth pattern from those with
      subnormal estrogen levels. STUDY DESIGN: Growth data from 78 full-term patients
      with Turner's syndrome were collected retrospectively. 24/78 later developed
      spontaneous puberty, (+Pub), and their growth data were compared to TS patients
      without spontaneous puberty (-Pub). A nonlinear mixed model was fitted using the
      bi-exponential model. RESULTS: The growth velocity difference between the -Pub
      and +Pub groups suggests an early infantile growth advantage in the -Pub group,
      which disappears before the end of the first year of life; growth velocity
      remains similar (+/- 1 cm/y) for the next 6 years and declines at age 7-8 years
      in the +Pub group faster than it does in the -Pub group. Bi-exponential analysis
      showed that both the 1st (restrictive) and 2nd exponent (forward) were different
      (p = 0.0003). CONCLUSIONS: Comparison of girls with or without spontaneous
      puberty suggests a role for estrogen in child growth. Estrogens restrict
      infantile growth, as well as growth during the mid-childhood spurt.

PMID- 15952085
TI  - Transient increase of plasma ghrelin after laparoscopic adjustable gastric
      banding in morbid obesity.
AB  - Ghrelin is a peptide hormone with orexigenic properties that is produced by the
      stomach. Ghrelin and leptin are thought to be the main regulators of appetite and
      body weight. The present study was aimed at evaluating the effect of weight
      reduction after laparoscopic adjustable gastric banding (LAGB) on metabolic
      parameters and energy balance regulatory peptides. Patients were evaluated before
      and 6, 12, 24 or 36 months after the procedure, and a blood sample was obtained.
      Ghrelin rose 6 and 12 months after LABG, and then returned to near-baseline
      levels. In our study, the correlation between ghrelin and BMI was weak, but a
      strong significant correlation was maintained between leptin and BMI. We conclude
      that ghrelin is mainly stimulated by the negative caloric balance, and
      hypothesize that ghrelin is involved in maintaining a stable body weight, while
      leptin signals the body energy store; both hormones together are part of a more
      complex feedback mechanism.

PMID- 15952086
TI  - Elevated serum GGT concentrations predict reduced insulin sensitivity and
      increased intrahepatic lipids.
AB  - Elevated serum gamma-glutamyltransferase (GGT) concentrations have been related
      to features of the metabolic syndrome as well as increased risk of cardiovascular
      and liver disease. More recently, elevated GGT levels were shown to predict
      development of type 2 diabetes in a longitudinal study from Korea. The aim of the
      present study was to test the hypothesis that serum GGT is associated with
      glucose tolerance, insulin sensitivity and beta-cell function in a healthy, non
      diabetic Caucasian population from the Tubingen family study. Insulin sensitivity
      was estimated by oGTT (n = 850) or measured by hyperinsulinemic euglycemic clamp
      (n = 245), respectively. A subgroup (n = 70) underwent additional determination
      of intrahepatic lipid content using 1H magnetic resonance spectroscopy. Serum GGT
      was positively correlated with two-hour glucose during oGTT (r = 0.15, p <
      0.0001) and negatively correlated with insulin sensitivity from oGTT (r = -0.31,
      p < 0.0001) and clamp (r = -0.27, p < 0.0001). The relationship between GGT and
      insulin sensitivity remained significant after adjusting for sex, age, BMI, and
      AST using multivariate regression analysis. Inclusion of serum triglyceride
      levels as a parameter of lipid metabolism kept the relationship significant in
      the oGTT group (p < 0.0001), but not in the smaller clamp group (p = 0.11).
      Additionally, serum GGT was positively correlated with hepatic lipid content (r =
      0.49, p < 0.001) independent of sex, age, BMI, AST or serum triglycerides. There
      was no significant correlation between GGT and the index for beta-cell function
      after adjusting for age, sex, BMI and insulin sensitivity (p = 0.74). In
      conclusion, elevated serum GGT levels predict glucose intolerance probably via
      insulin resistance rather than beta-cell dysfunction. This may be primarily
      related to hepatic insulin resistance and increased intrahepatic lipids. The
      association observed between elevated hepatic lipids and reduced insulin
      sensitivity might explain the increased diabetes risk observed in subjects with
      elevated serum GGT concentrations. In the absence of overt liver disease,
      elevated serum GGT concentrations may point the clinician to incipient
      disturbances in the glucose metabolism.

PMID- 15952087
TI  - Pentosidine plasma levels and relation with metabolic control in diabetic
      patients.
AB  - Levels of plasma pentosidine, a well-known AGE, were measured in type 2 diabetic
      patients in varying states of metabolic control to verify possible relationships
      between this parameter and traditional metabolic control parameters such as HbA1c
      and plasma glucose levels. At baseline, mean values of fasting plasma glucose,
      HbA1c and pentosidine were significantly higher in diabetic patients than those
      of controls, confirming patients' poor glycemic control. After ten months,
      patients with good metabolic control achieved showed near-normal HbA1c levels and
      reduced but not normalized pentosidine levels. Significant differences were found
      in the mean percentage decrease in the parameters. Regarding linear correlation,
      HbA1c levels only showed a positive relationship with plasma glucose values at
      baseline. Patients affected by chronic complications showed higher levels of
      pentosidine than those without complications. Thus, pentosidine plasma levels may
      be used to evaluate very long-term metabolic control in diabetic patients. In
      addition, a period of ten months of acceptable metabolic control is not enough to
      normalize pentosidine levels in diabetics, thus emphasizing the need for a longer
      period of improved metabolic control to reduce both this parameter and the burden
      of chronic diabetic complications.

PMID- 15952088
TI  - Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C
      174G in patients with type 2 diabetes and controls.
AB  - The relationship between humoral immunity to hsp60 and type 2 diabetes along with
      other relevant metabolic, inflammatory and immunogenetic variables was studied in
      76 non-diabetic and 74 diabetic persons aged 55-74 years selected from the
      population-based KORA Survey 2000. Antibodies to human hsp60 were measured in
      serum samples by ELISA. Hsp60 antibodies were detected in all but two individuals
      in a considerable range of titres (22-1,856 AU/ml). There was no significant
      association to age and sex, or to key clinical or metabolic parameters (BMI, WHR,
      HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, systolic and
      diastolic blood pressure, albumin, uric acid) or immunological parameters (CRP,
      IL-6, sIL-6R, TNFalpha, sTNFalpha R60, sTNFalpha R80). Analysis of antibody
      positive individuals revealed an association between hsp60 antibodies and
      diabetes at borderline significance (p = 0.047), which was lost when the two
      antibody-negative individuals were included. Genetic analyses indicated that this
      association was significant in carriers of the C allele of the IL-6 promoter
      region polymorphism at nucleotide -174 (p = 0.02), but not in GG genotype
      carriers. We conclude that humoral immunity to human hsp60 may be enhanced in
      those diabetic patients carrying the -174C allele of the IL-6 gene. This finding
      may contribute to an understanding of the relationship between the -174C allele
      and increased risk of atherosclerosis.

PMID- 15952089
TI  - Dysregulation of chondrogenesis in human cleidocranial dysplasia.
AB  - Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal dysplasia caused
      by heterozygosity of mutations in human RUNX2. The disorder is characterized by
      delayed closure of the fontanel and hypoplastic clavicles that result from
      defective intramembranous ossification. However, additional features, such as
      short stature and cone epiphyses, also suggest an underlying defect in
      endochondral ossification. Here, we report observations of growth-plate
      abnormalities in a patient with a novel RUNX2 gene mutation, a single C insertion
      (1228insC), which is predicted to lead to a premature termination codon and thus
      to haploinsufficiency of RUNX2 and the CCD phenotype. Histological analysis of
      the rib and long-bone cartilages showed a markedly diminished zone of
      hypertrophy. Quantitative real-time reverse transcription-polymerase chain
      reaction analysis of limb cartilage RNA showed a 5-10-fold decrease in the
      hypertrophic chondrocyte molecular markers VEGF, MMP13, and COL10A1. Together,
      these data show that humans with CCD have altered endochondral ossification due
      to altered RUNX2 regulation of hypertrophic chondrocyte-specific genes during
      chondrocyte maturation.

PMID- 15952090
TI  - Protein-losing enteropathy in Crohn's disease.

PMID- 15952091
TI  - Schistosomiasis.

PMID- 15952092
TI  - Update on chronic hepatitis C.
AB  - The burden of chronic hepatitis C infection remains significant in the United
      States and worldwide. Increased knowledge regarding the natural history of acute
      and chronic infection and the key factors responsible for disease progression,
      risk for cirrhosis, and risk for hepatocellular carcinoma are critical in guiding
      secondary and tertiary prevention measures. The past decade has seen substantial
      improvement of antiviral therapy for chronic hepatitis C virus with an increasing
      number of individuals achieving viral eradication. Decisions regarding whom,
      when, and how to use antiviral therapy have become more complex and change as new
      studies become available. This review focuses on the current status of hepatitis
      C virus patient management and future treatment directions.

PMID- 15952093
TI  - Psychosocial correlates of symptoms in functional dyspepsia.
AB  - BACKGROUND & AIMS: Psychosocial factors may influence both symptom generation and
      reporting in functional dyspepsia. We determined the presence and severity of
      these factors as well as their relationship to dyspeptic symptoms in patients
      with functional dyspepsia and healthy subjects. METHODS: A total of 151
      consecutive patients with functional dyspepsia referred chiefly from primary care
      clinics and 90 healthy subjects rated 15 dyspeptic symptoms. Participants
      completed the Medical Outcomes Study SF-36 and Symptom Checklist-90-revised.
      RESULTS: Functional dyspepsia patients reported significantly higher symptom
      scores, poorer quality of life, and greater psychiatric distress than healthy
      subjects. For both patients and healthy subjects, increasing symptom scores were
      associated with significant decreases in the Physical but not the Mental
      Components Summary of the Medical Outcomes Study SF-36. Although functional
      dyspepsia patients showed significantly greater psychiatric distress than healthy
      subjects, symptoms were correlated only modestly with scores on the Symptom
      Checklist-90-revised. A number of symptoms showed significant but modest
      correlations ( r s < .30) with the somatization scale with chest burning
      correlating most strongly ( r s = .48). Chest burning also was correlated
      significantly with depression, anxiety, and phobic anxiety. Functional dyspepsia
      patients at a secondary level of care have greater symptom severity, poorer
      quality of life, and greater psychiatric distress than healthy subjects.
      Increasing symptom severity is associated with poorer quality of life primarily
      in the areas of physical and social functioning. With the exception of chest
      burning, symptoms are not correlated highly with psychiatric distress.
      CONCLUSIONS: These data suggest that although functional dyspepsia patients
      experience increased psychiatric distress, symptom severity and psychiatric
      distress are not associated strongly.

PMID- 15952094
TI  - Complex diseases in gastroenterology and hepatology: GERD, Barrett's, and
      esophageal adenocarcinoma.
AB  - Gastroesophageal reflux disease, Barrett's esophagus, and esophageal
      adenocarcinoma are related diseases with environmental and genetic determinants.
      The genetic changes are relevant in 2 distinct ways. First, there are heritable
      variations in germline DNA that may influence the individual susceptibility to
      cancer. Second, there is an accumulation of somatic-cell genetic and epigenetic
      changes within the epithelium during the metaplasia-dysplasia-carcinoma sequence,
      which may be an important determinant for the likelihood for cancer progression.
      Esophageal cancer occurring in the context of a familial syndrome is rare and
      most cases are sporadic. The sporadic cases still may have heritable germline
      influences, but these are likely to involve multiple, low-penetrance
      susceptibility genes. To date, the relative contribution and identity of such
      genes are unknown. However, in the future the identification of susceptibility
      genes could have important public health implications for patient management.
      With regard to the epithelium, a map gradually is being created of the frequently
      occurring alterations. Some of these changes are critical whereas others are
      bystanders. As well as the identification of abnormalities in target genes, it
      also is possible to determine the global gene expression profile of these
      diseases and to correlate this profile with clinical outcome. It is hoped that
      these complementary approaches will enable patients to be stratified in terms of
      their cancer risk so that prevention, surveillance, and treatment strategies can
      be targeted appropriately. At the current time, genetics does not influence
      routine clinical management of patients with gastroesophageal reflux disease,
      Barrett's esophagus, or esophageal adenocarcinoma.

PMID- 15952095
TI  - Abdominal pain with fluctuating elevation of amylase and AST.

PMID- 15952096
TI  - Prevalence and socioeconomic impact of upper gastrointestinal disorders in the
      United States: results of the US Upper Gastrointestinal Study.
AB  - BACKGROUND & AIMS: This study examined the prevalence of upper gastrointestinal
      (GI) symptoms and symptom groupings and determined impact on disability days in a
      nationally representative US sample. METHODS: A telephone survey of 21,128 adults
      was conducted including questions about the presence of upper GI symptoms during
      the past 3 months. Respondents were categorized as symptomatic (ie, reported GI
      symptoms once per month) or asymptomatic. The survey included questions about
      missed work, leisure activity, or household activity days. Symptom groupings were
      identified by using factor analysis, and cluster analysis was used to assign
      respondents into distinct groups on the basis of these symptom groupings.
      RESULTS: The prevalence of an average of 1 or more upper GI symptoms during the
      past 3 months was 44.9%. The most common symptoms experienced during the past 3
      months were early satiety, heartburn, and postprandial fullness. Factor analysis
      identified 4 symptom groupings: (1) heartburn/regurgitation; (2) nausea/vomiting;
      (3) bloating/abdominal pain; and (4) early satiety/loss of appetite. Five
      respondent clusters were identified; the largest clusters were primarily early
      satiety/fullness (44%) and gastroesophageal reflux disease-like symptoms (28%).
      Two small clusters reflected nausea and vomiting (7%) and a heterogeneous symptom
      profile (4%). Symptomatic respondents reported significantly more missed work,
      leisure, and household activity days than asymptomatic respondents (all P <
      .0001). CONCLUSIONS: Factor analysis separated GI symptoms into groupings
      reflecting gastroesophageal reflux disease and dyspepsia: early satiety,
      postprandial fullness, and loss of appetite; bloating and abdominal
      pain/discomfort; and nausea and vomiting. These upper GI symptoms were associated
      with significant loss of work and activity days.

PMID- 15952097
TI  - Early heartburn relief with proton pump inhibitors: a systematic review and meta
      analysis of clinical trials.
AB  - BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are often taken for short-term
      treatment of heartburn. We performed a systematic review of the efficacy of PPIs
      for heartburn relief within the first 1-2 days of therapy. METHODS: Bibliographic
      databases were searched for clinical trials of PPIs in patients with heartburn
      that provided information about the proportion with heartburn relief at day 1-2.
      The sample size-weighted pooled proportions of patients with complete or
      sustained (7 consecutive days) relief were calculated. Meta-analyses of
      randomized comparisons of PPIs were also performed. RESULTS: Eighteen trials met
      inclusion criteria. At day 1 of PPI therapy, complete 24-hour, daytime,
      nighttime, and sustained heartburn relief occurred in 0.31 (95% confidence
      interval [CI], 0.30-0.32), 0.49 (95% CI, 0.48-0.50), 0.55 (95% CI, 0.53-0.56),
      and 0.21 (95% CI, 0.20-0.22) of patients. Up to 37% of the heartburn relief
      achievable with 28 days of PPIs occurred on day 1. Placebo was significantly less
      effective than PPIs for 24-hour relief on day 1 (relative risk [RR], 0.41; 95%
      CI, 0.29-0.58), and single-dose PPI therapy was less effective than double-dose
      therapy (RR, 0.82; 95% CI, 0.74-0.92). CONCLUSIONS: Complete heartburn relief for
      the entire day occurs in approximately 30% of patients after their first PPI dose
      and 9% of patients after their first placebo (RR for relief on day 1 for placebo
      versus PPI was 0.41 [95% CI, 0.28-0.58]). Although PPIs might provide benefit
      from the first day of therapy, most patients will not have symptom relief with 1
      or 2 days of PPI therapy.

PMID- 15952098
TI  - Influence of CYP2C19 polymorphism and Helicobacter pylori genotype determined
      from gastric tissue samples on response to triple therapy for H pylori infection.
AB  - BACKGROUND & AIMS: The relationship between single nucleotide polymorphisms
      (SNPs) and clinical outcomes has been intensively studied. We intended to
      determine SNPs of CYP2C19 and 23S rRNA of Helicobacter pylori by using rapid
      urease test (RUT)-positive gastric mucosal samples. METHODS: One hundred thirty
      nine patients with H pylori -positive results based on RUT completed 1-week
      treatment with lansoprazole 30 mg twice a day, clarithromycin 200 mg 3 times
      daily, and amoxicillin 500 mg 3 times daily. SNPs from adenine to guanine at
      positions 2142 and 2143 of 23S rRNA of H pylori (A2142G and A2143G) and SNPs from
      guanine to adenine at positions 681 in exon 5 (* 2 ) and 636 in exon 4 (* 3 ) of
      CYP2C19 were determined by the serial invasive signal amplification reaction
      assay by using DNAs extracted from gastric tissue samples already used for RUT.
      Minimum inhibitory concentrations of clarithromycin for H pylori were determined
      by culture test. CYP2C19 genotypes were classified into the rapid metabolizer (*
      1 /* 1 ), intermediate metabolizer (* 1 /* 2 or * 1 /* 3 ), and poor metabolizer
      (* 2 /* 2 , * 2 /* 3 , or * 3 /* 3 ) groups. RESULTS: H pylori strains with
      A2142G or A2143G mutation had higher minimum inhibitory concentrations for
      clarithromycin. Cure rates in rapid, intermediate, and poor metabolizer groups
      were 57.8% (95% confidence interval, 42.1%-72.4%), 88.2% (78.1%-94.8%), and 92.3%
      (74.9%-99.1%), respectively ( P < .001). Cure rates in strains with and without
      A2142G or A2143G mutation were 48.3% (29.4%-67.5%) and 87.3% (79.5%-92.7%),
      respectively ( P < .001). CONCLUSIONS: SNPs of CYP2C19 and 23S rRNA of H pylori
      using RUT-positive gastric mucosal samples could be predictable determinants for
      H pylori eradication by triple therapy.

PMID- 15952099
TI  - Prevalence of hyperhomocysteinemia in adult gluten-sensitive enteropathy at
      diagnosis: role of B12, folate, and genetics.
AB  - BACKGROUND & AIMS: Hyperhomocysteinemia, a risk factor for thrombosis, recurrent
      miscarriages, and osteoporosis, might derive from acquired folate and vitamin B
      12 deficiencies and from a C677T mutation in methylene-tetrahydrofolate reductase
      (MTHFR) gene. Undiagnosed gluten-sensitive enteropathy (GSE) is associated with
      vitamin deficiencies, osteoporosis, and recurrent miscarriages. We evaluated the
      prevalence and the risk factors for hyperhomocysteinemia in patients with newly
      diagnosed GSE. METHODS: In this prospective study performed in a tertiary care
      setting, 40 consecutive subjects with newly diagnosed GSE were evaluated for
      homocysteine, folate, and vitamin B 12 levels and for C677T polymorphism. One
      hundred twenty sex- and age-matched healthy control subjects were studied.
      Nonparametric tests and multiple regression analysis were used to evaluate the
      risk factors in inducing hyperhomocysteinemia in the GSE population. RESULTS:
      Hyperhomocysteinemia was more frequent in GSE patients than in control subjects
      (8/40, 20.0% vs 7/120, 5.8%) (relative risk, 3.4; 95% confidence interval, 1.3
      8.9), as well as folate deficiency (17/40, 42.5% vs 10/120, 8.3%) (relative risk,
      5.1; 95% confidence interval, 2.5-10.2). Multiple regression analysis showed that
      folate and B 12 levels were independently and inversely associated with
      homocysteine levels, whereas homozygosity for the MTHFR thermolabile variant was
      not. The prevalence of MTHFR variant in GSE population was not different from
      that reported in racially comparable control groups. Gluten-free diet was able to
      normalize folate, vitamin B 12 , and homocysteine levels. CONCLUSIONS:
      Hyperhomocysteinemia is frequent in newly diagnosed GSE. Vitamin deficiencies
      caused by malabsorption are the most important determinants of this condition.
      Hyperhomocysteinemia might contribute to the occurrence of common complications
      of undiagnosed GSE.

PMID- 15952100
TI  - Interferon-beta-1a for the treatment of steroid-refractory ulcerative colitis: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND & AIMS: We performed a randomized, double-blind, placebo-controlled,
      multicenter trial to investigate the efficacy and safety of recombinant
      interferon-beta-1a (rIFN-beta-1a) in outpatients with active steroid-refractory
      ulcerative colitis. METHODS: Ninety-one randomized patients subcutaneously
      received 3 MIU rIFN-beta-1a (group A, n = 32), 1 MIU rIFN-beta-1a (group B, n =
      30), or placebo (group C, n = 29) 3 times a week over a period of 8 weeks in
      addition to standard therapy. An intention-to-treat analysis was performed to
      evaluate the efficacy and safety of treatment. RESULTS: In all 3 groups, the
      median prestudy clinical activity index (CAI) was 10. In 18 of 32 patients (56%)
      in group A, in 11 of 30 patients (36%) in group B, and in 10 of 29 patients (34%)
      in group C, a reduction of the CAI of 6 points or greater (response) was achieved
      (differences were not statistically significant). Complete response (reduction of
      CAI to < or =4) was achieved in 56%, 30%, and 38% of patients in groups A, B, and
      C, respectively. Compared with baseline, the median endoscopic index had been
      reduced by 5, 3, and 4 points in groups A, B, and C, respectively. Steroid
      reduction was 12 mg in group A, 6 mg in group B, and 10 mg in group C. Identical
      side effects occurred in all 3 groups. Seven serious adverse events were reported
      (1 in group A and 6 in group C). All were unrelated to therapy as judged by the
      investigating physicians. CONCLUSIONS: rIFN-beta-1a was safe but not significant,
      at the dosage and/or duration of treatment used, in steroid-refractory ulcerative
      colitis. Further studies are indicated.

PMID- 15952101
TI  - Type 2 diabetes mellitus and the risk of colorectal cancer.
AB  - BACKGROUND & AIMS: Type 2 diabetes mellitus might increase the risk of colorectal
      cancer on the basis of chronic hyperinsulinemia and hyperglycemia. However,
      epidemiologic evidence for this association is inconclusive. We conducted a
      population-based study to clarify this association. METHODS: We conducted a case
      control study in the United Kingdom General Practice Research Database. Cases
      included all patients with incident colorectal cancer diagnoses (n = 10,447). Up
      to 10 control subjects were selected for each case, matching on year of birth,
      enrollment date, and duration of database follow-up. The exposure of interest was
      type 2 diabetes mellitus. Odds ratios (ORs) were calculated by using conditional
      logistic regression. RESULTS: A prior diagnosis of type 2 diabetes mellitus was
      associated with a modestly increased risk of colorectal cancer (OR, 1.42; 95%
      confidence interval [CI], 1.25-1.62). The association between type 2 diabetes
      mellitus and colorectal cancer was observed in both men (OR, 1.36; 95% CI, 1.16
      1.61) and women (OR, 1.38; 95% CI, 1.14-1.67). The risk increase was observed in
      both colon (OR, 1.45; 95% CI, 1.25-1.70) and rectal (OR, 1.34; 95% CI, 1.08-1.68)
      cancers. CONCLUSIONS: Type 2 diabetes mellitus is associated with an increased
      risk of colorectal cancer. The risk increase is present in both sexes, as well as
      in both colonic and rectal cancers.

PMID- 15952102
TI  - Susceptibility to thyroid disorders in hepatitis C.
AB  - BACKGROUND & AIMS: Autoimmune thyroid disorders (AITDs) are reported, especially
      during interferon treatment, in chronic HCV infection, in which non-organ
      specific autoantibodies (NOSAs) are common. We wondered whether seropositivity
      for NOSA is associated with susceptibility to AITDs. METHODS: We evaluated
      thyroid function and antithyroglobulin and antithyroperoxidase antibodies in 348
      Italian patients with chronic hepatitis C (34% NOSA-positive), 196 patients (33%
      NOSA-positive) of whom received interferon treatment. RESULTS: At baseline,
      thyroid disorders were significantly more frequent in liver/kidney microsomal
      antibody type 1 (LKM1)-positive patients (29% vs 9%, P < .005). Similarly, on
      interferon therapy de novo autoimmune thyroid markers and/or symptomatic thyroid
      disorders appeared more often in LKM1-positive patients (50% vs 3%, P < .0001).
      Both female sex and LKM1 positivity were predictors of AITD, but only the latter
      remained significant after logistic regression analysis. Cross-reactivity to all
      7 linear epitopes encoding homologous amino acid sequences shared by the HCV
      polyprotein, CYP2D6 (the LKM1 autoantigen), and thyroperoxidase was detected in
      86% LKM1-positive HCV patients with clinical thyroid disorders, but in none of
      the LKM1-positive or negative HCV patients without thyroid disease, and none of
      an HCV-negative control group comprising subjects with LKM1-positive autoimmune
      hepatitis or AITD without liver disease ( P < .0001). CONCLUSIONS: Patients
      receiving interferon therapy for hepatitis C seropositive for LKM1 are
      susceptible to develop AITDs, in association with treatment. Molecular mimicry
      and epitope spreading are potential pathogenic mechanisms.

PMID- 15952103
TI  - Effect of significant histologic steatosis or steatohepatitis on response to
      antiviral therapy in patients with chronic hepatitis C.
AB  - BACKGROUND & AIMS: Treatment of chronic hepatitis C (CHC) results in an average
      sustained viral response (SVR) rate of 54%-63%. Most previous studies have not
      separately reported SVR rates for patients who have CHC and concomitant
      significant hepatic steatosis (>33%) or histologic evidence of steatohepatitis
      (SH). The aim of this study was to evaluate SVR in patients with CHC plus
      steatosis or SH on biopsy examination, compared with a group of controls with CHC
      and no significant steatosis or SH. METHODS: Our surgical pathology database and
      clinical files were queried for CHC between 1997 to 2002. Biopsy specimens with
      both CHC and significant steatosis (>33%) or SH were categorized as group 1. Of
      the patients treated with antiviral therapy, information on either SVR (hepatitis
      C virus [HCV] RNA negative at 6 months posttreatment) or lack of SVR (nonresponse
      as early as 12 weeks into therapy and relapsers) with either interferon
      (IFN)/ribavirin or pegylated IFN/ribavirin was found in 84 patients. A control
      group (group 2) of 231 CHC patients was identified by using a 2-year database
      (January 2000-June 2001) of patients without evidence of greater than 33%
      steatosis or SH. RESULTS: The overall SVR was 28% in group 1, compared with 44%
      for group 2 ( P = .001). For HCV genotype 1, the SVR was 23% vs 34% for group 2 (
      P = .19). For HCV genotypes 2 and 3, the SVR was 42% vs 78% for groups 1 and 2 (
      P = .008), respectively. CONCLUSIONS: Overall SVR for patients with HCV and
      significant steatosis or SH is considerably lower than for HCV and steatosis less
      than 33% and no SH.

PMID- 15952104
TI  - Optimal dosing frequency of pegylated interferon alfa-2b monotherapy for chronic
      hepatitis C virus infection.
AB  - BACKGROUND & AIMS: Pegylated interferon alfa-2b (PEG-IFN-alfa 2b ) has been shown
      to provide superior efficacy to IFN-alfa 2b in patients with chronic hepatitis C
      (predominantly genotype 1) infection as measured by viral clearance. This study
      was conducted to determine the optimal dosing regimen of PEG-IFN-alfa 2b required
      to obtain a maximum decrease of hepatitis C viral RNA. METHODS: This was a 24
      week, open-label, multicenter, parallel-group, randomized, active-controlled
      trial in the United Kingdom, France, and Israel. Individuals (n = 61) with
      chronic hepatitis C infection, genotype 1, received IFN-alfa 2b 3 mIU 3 times
      weekly for 24 weeks, or PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk, as total weekly
      full or split doses, for 12 weeks. At week 12, serum RNA titer was measured, and
      all PEG-IFN-alfa 2b patients continued with 1.5 microg/kg/wk for a further 12
      weeks. RESULTS: Mean serum hepatitis C RNA levels decreased in all groups at
      weeks 12 and 24. PEG-IFN-alfa 2b 1.5 microg/kg/wk was superior to IFN-alfa 2b in
      decreasing mean serum hepatitis C RNA ( P < .05 at week 12). The efficacy of
      split-dose PEG-IFN-alfa 2b 1.5 or 3.0 microg/kg/wk regimens was not significantly
      different from full-dose PEG-IFN-alfa 2b 1.5 microg/kg/wk. However, there was a
      significant decrease in neutrophil count in groups receiving PEG-IFN-alfa 2b 3.0
      microg/kg/wk or lower, multiple-dose per week regimens. CONCLUSIONS: PEG-IFN-alfa
      2b 1.5 microg/kg once weekly is the optimal dosing frequency for patients with
      chronic hepatitis C with predominantly genotype 1 infection. More frequent dosing
      or increasing the dose to 3.0 microg/kg/wk did not result in improved antiviral
      effects, but did decrease neutrophil counts.

PMID- 15952105
TI  - Research on screening and identification of proteins interacting with ataxin-3.
AB  - OBJECTIVE: This study sought to isolate and identify the proteins that interact
      with ataxin-3, to confirm the interacted domain, and to provide new clues for
      exploring the function of ataxin-3 and the pathogenesis of spinocerebellar ataxia
      type 3 and Machado-Joseph disease (SCA3/MJD). METHODS: Yeast two-hybrid screen
      (MATCHMAKER GAL4 Two-Hybrid System 3) and regular molecular biologic techniques
      were undertaken to screen human brain cDNA library with mutant ataxin-3 bait. Two
      baits from both normal and mutant C-terminus of ataxin-3 were created by
      subcloned methods to determine which domain of ataxin-3 interacts with the
      putative associated proteins and to find out optimal candidate proteins that
      interact with C-terminus of ataxin-3. Confocal microscope was used to observe
      whether ataxin-3 co-localized with the obtained interacting proteins in mammalian
      cells. RESULTS: Five novel ataxin-3 interacting proteins were obtained, among
      which were three known proteins, namely human rhodopsin guanosine diphosphate
      dissociation inhibitor alpha, small ubiquitin-like modifier 1, and human neuronal
      amiloride-sensitive cation channel 2; the other two were unknown. Interacting
      domain analysis revealed that an unknown protein interacted with the C-terminus
      near the polyglutamine tract of ataxin-3, the other four all interacted with the
      N-terminus. In the nucleus of SH-SY5Y cell, small ubiquitin-like modifier 1 co
      localized with the wild-type ataxin-3 and with the intranuclear aggregates formed
      by the mutant ataxin-3. CONCLUSION: An unknown protein probably interacting with
      C-terminus of ataxin-3 is firstly discovered, and the initiative findings suggest
      first that the interaction of small ubiquitin-like modifier 1 with N-terminus of
      ataxin-3 and the relevant sumoylation probably participate in the post
      translation modifying of ataxin-3 and in the pathogenesis of SCA3/MJD.

PMID- 15952106
TI  - Expression of a novel human retroviral NP9 gene and potential roles of its
      protein in systemic lupus erythematosus patients.
AB  - OBJECTIVE: To investigate the expression of a novel retroviral (NP9) gene
      transcripts and the possible role of its protein in systemic lupus erythematosus
      (SLE) patients. METHODS: The retroviral NP9 gene in SLE patients was isolated and
      cloned using RT-PCR and TA cloning techniques, and it was analyzed by sequencing.
      The expression of the NP9 genes in 40 patients with SLE and 48 normal controls
      using RT-PCR was detected. NCBI BLAST and DNASIS 3.1 software were used to
      analyze the features of protein of NP9 gene. RESULTS: The positive ratio (77.5%)
      of the mRNA expression of the retroviral NP9 gene in SLE patients is
      significantly higher than that (8.3%) in normal subjects (P<0.01). The
      recombinant NP9 protein comprises 74 AA with pI 9.59. Amino acid sequence
      analysis indicates that the retroviral NP9 protein shares higher homologies with
      several human proteins with important biological functions. CONCLUSION: SLE
      patients possess specific novel retroviral NP9 transcripts. The expression of the
      retroviral NP9 gene may involve in the genesis or development of SLE.

PMID- 15952107
TI  - Mutation of acceptor splice site of the SEDL gene in X-linked spondyloepiphyseal
      dysplasia tarda causes the activation of cryptic splice site.
AB  - OBJECTIVE: To further investigate the genetic basis of hereditary X-linked
      spondyloepiphyseal dysplasia tarda (SEDL) and provide useful information for the
      prevention and treatment of the disease. METHODS: RT-PCR and cDNA sequencing were
      used to test mRNA expression of SEDL gene in a patient with 13 bp deletion of
      SEDL gene involving the acceptor splice site of intron 5. RESULTS: Of two
      different sizes of mRNA products identified in the patient, the 393 bp product
      was created due to the activation of cryptic splice site within exon 6; the 433
      bp product was completely consistent with the part of genomic sequence on
      chromosome 8. CONCLUSION: The intragenic deletion that occurred in the acceptor
      splice site of the 3'region of intron 5 and the 5' coding region of exon 6
      results in the activation of a cryptic splice site within exon 6, which causes 47
      bp deletion of the resulting mRNA followed by a frameshift that would add two
      missense amino acids and then be followed by a termination codon (D109-S123del;
      S124fsX126). In addition, the mutation may activate the transcription of
      pseudogene SEDLP2 on chromosome 8 to partly complement the function of SEDL
      protein.

PMID- 15952108
TI  - Detection of chromosome aberrations in Chinese children with autism using G
      banding and BAC FISH.
AB  - OBJECTIVE: To detect the characteristic chromosomal changes in Chinese children
      with infantile autism. METHODS: Chromosome aberrations in 68 cases of infantile
      autism were analyzed by high-resolution G-banding and fluorescence in situ
      hybridization (FISH) with bacterial artificial chromosome (BAC) clones. RESULTS:
      Chromosomal changes were detected in 4 cases by high-resolution G-banding: one
      case with t(4;6)(q23-24;p21), one case with longer p arm of chromosome 21 (21p+),
      and two cases with pericentric inversion of chromosome 9 (inv(9)) which was
      confirmed by C-banding. BAC FISH analysis was performed to confirm these
      observations and changes in chromosomes 2, 7 and 15, which are often found in
      autistic children. There could exist the translocation of t(4;6) (q25-26;p21.1).
      Chromosome changes often reported previously in chromosomes 2, 7 and 15 were not
      detected in this study. Inv(9) and 21p+ were not confirmed with present BAC
      clones. CONCLUSION: Chromosomal changes were detected in four cases of infantile
      autism, with a detectability of 5.9% , far lower than that (10% to 48%) reported
      in literature. The breakpoint of translocation could be detected more accurately
      using BAC FISH method.

PMID- 15952109
TI  - Screening for ZNF230 gene mutation and analysis of its correlation with
      azoospermia.
AB  - OBJECTIVE: To investigate the possible association between ZNF230 gene and
      azoospermia. METHODS: Screening for mutation of all 6 exons of ZNF230 gene was
      performed by denaturing high performance liquid chromatography(DHPLC) in 99
      patients with azoospermia and in 115 healthy men as controls. RESULTS: An A-->G
      transition at nucleotide 316 in exon 6 was identified. There were significant
      differences in the distribution profiles of both allele and genotype frequencies
      between patient group and control group (P < 0.01 and P < 0.05, respectively). In
      addition,there was a statistically significant difference in the serum follicle
      stimulating hormone (FSH) level between the patients with GG/GA genotype and
      those with AA genotype (P < 0.05). CONCLUSION: ZNF230 gene may be associated with
      azoospermia, and the A316G mutation may be correlated with the serum FSH level.

PMID- 15952110
TI  - Analysis of germline mutations in the APC gene in familial adenomatous polyposis
      patients.
AB  - OBJECTIVE: This study was aimed at establishing an efficient mutation analysis
      technique system to screen the germline mutations in the adenomatous polyposis
      coli (APC) gene that predisposes the disease susceptibility in familial
      adenomatous polyposis (FAP) and to investigate the relationship between genotype
      and phenotype of APC gene. METHODS: Genomic DNA was extracted from the peripheral
      blood lymphocytes of 22 patients with clinically diagnosed FAP and was forwarded
      to screening for germline mutations by using denaturing high-performance liquid
      chromatography(DHPLC), protein truncation test (PTT) and DNA sequencing in APC
      gene. Analysis of genotype-phenotype was also performed on the clinical data of
      the FAP patients. RESULTS: Thirteen APC germline mutations were identified in 22
      FAP patients. All of the mutations were nonsense or framshift mutations. Analysis
      of genotype-phenotype demonstrated that the FAP patients with mutations in the
      5'or 3'extreme parts of the APC gene showed mild clinical symptoms. However, the
      FAP patients with mutations in the middle of the APC gene displayed typical or
      severe clinical symptoms. CONCLUSION: The technique system established in this
      study can efficiently and sensitively detect the mutations in APC gene. It is
      useful in the molecular diagnosis of pre-symptomatic FAP cases in FAP family. The
      clinical features of FAP patients may be related to their genotypes of APC gene.

PMID- 15952111
TI  - Expression of imprinted genes related to Beckwith-Wiedemann syndrome in human
      oocytes and preimplantation embryos.
AB  - OBJECTIVE: To investigate the expression of imprinted genes related to Beckwith
      Wiedemann syndrome (BWS) in human oocytes and preimplantation embryos for
      understanding the relationship between assisted reproductive technology (ART) and
      BWS. METHODS: Using nested reverse transcription-PCR to analyze the expression of
      P57KIP2, LIT1, TSSC3 in human oocytes and preimplantation embryos. RESULTS:
      Transcripts of P57KIP2 were detected in human oocytes and at all stages of
      preimplantation embryos. LIT1 was expressed only in stages of 8-cell and
      blastocyst. Transcripts of TSSC3 could not be detected in human oocytes and
      preimplantation embryos. CONCLUSION: Transcripts of P57KIP2 and LIT1, imprinted
      genes related to BWS, were detected in human preimplantation development; ART
      might affect the epigenetics of imprinted genes in early embryogenesis.

PMID- 15952112
TI  - Genetic polymorphisms of four STR loci on chromosome X and their forensic
      applications in a Chinese Han population.
AB  - OBJECTIVE: To add DXS7133, GATA198A10, DXS9896 and DXS6797 to the panel of
      forensically validated X chromosome markers, and apply the multiplex
      amplification system to a population study and forensic analysis on the Hans of
      Chengdu. METHODS: The PCR products were detected by the polyacrylamide gel
      electrophoresis and silver staining method. Hardy-Weinberg equilibrium of females
      was tested and every forensically interested value was calculated. RESULTS:
      Sequencing revealed that their common sequence motifs were tetranucleotide
      repeats. Population genetic data were obtained by analyzing 120 unrelated females
      and 100 males from Chengdu Han ethnic group. In this population, DXS7133,
      GATA198A10, DXS9896 and DXS6797 exhibited 6, 6, 11, 8 distinguishable alleles
      respectively. Chi-square test demonstrated that genotype frequencies in females
      did not depart from Hardy-Weinberg equilibrium. Power of discrimination for
      female samples for the four loci were 0.7962, 0.8021, 0.9675, and 0.9444. The
      parentage testing in 32 cases revealed a typical X-linked inheritance and no
      mutations. CONCLUSION: DXS7133, GATA198A10, DXS9896 and DXS6797, which are highly
      polymorphic in Chengdu Han population, are appropriate for individual
      identification and paternity testing involving a female child.

PMID- 15952113
TI  - Effect of the interaction between paranoxonase 1 and ATP-binding cassette
      transporter 1 gene polymorphism on serum lipid level.
AB  - OBJECTIVE: To investigate the effect of interaction between paranoxonase 1
      (PON1)gene polymorphism and ATP-binding cassette transporter 1 (ABCA1) genetic
      variation on serum lipid level. METHODS: Polymerase chain reaction-restricted
      fragments length polymorphism was used to determine PON1 A/B192 and ABCA1R219K
      genotype of 1019 subjects, including 680 patients with strokes and 339 healthy
      individuals as controls. RESULTS: No significant association between A/B192
      genotype and any of the lipid measurements was detected. The levels of HDL-C in
      the subjects with RR, RK and KK genotypes showed a significant upward tendency
      respectively (P < 0.05); the levels of their triglyceride (TG) tended downward
      respectively, but there were no significant differences between them. The
      relationship between R219K genotype and serum lipid level was modified by A/B192
      genotype. The levels of HDL-C in the subjects with AA/RR genotype and BB/KK
      genotype [(1.41 +/- 0.40) mmol/L, (1.41 +/- 0.39) mmol/L] were significantly
      different from that in the subjects with BB/RR genotype [(1.28 +/- 0.36) mmol/L]
      (P < 0.05). CONCLUSION: The result exhibited an interaction of PON1 A/B192 and
      ABCA1 R219K on serum lipid level.

PMID- 15952115
TI  - Association between apolipoprotein A5 - 1131T > C polymorphism and susceptibility
      of coronary artery disease in Chinese.
AB  - OBJECTIVE: To investigate the relationship between apolipoprotein A5(apoA5) -
      1131T > C polymorphism and the susceptibility of coronary artery disease (CAD) in
      Chinese. METHODS: The restriction fragment length polymorphism of apoA5 gene -
      1131T > C was studied using PCR in a case-control study which enrolled 235
      patients with CAD diagnosed by angiography and 262 healthy controls from Jiangsu
      province. RESULTS: The frequencies of T, C allele were 59.57%i40.43% and 65.65%,
      34.35% in CAD group and control group respectively. There was statistically
      significant difference in allele frequencies between CAD group and control group
      (P < 0.05). The susceptibility to CAD for the CC genotype was much higher than
      that for wild type TT (OR = 1.872, 95% CI = 1.039 - 3.376, P = 0.037), even after
      the use of Logistic regression models (OR = 2.285, 95% CI = 1.222 - 4.274, P =
      0.012). In control group, there was significant difference in TG levels among
      different genotypes, the C allele carriers had higher serum TG concentration (P =
      0.007). CONCLUSION: apoA5 - 1131T > C polymorphism is associated with an
      increased risk of CAD and is also in strong association with serum TG levels.

PMID- 15952114
TI  - Mutation analysis of HOXD13 gene in a Chinese pedigree with synpolydactyly.
AB  - OBJECTIVE: To study the clinical features and to identify homeobox D13 (HOXD13)
      gene mutation of the affected individuals in a Chinese synpolydactyly (SPD)
      kindred. METHODS: Clinical data and peripheral blood samples of SPD family
      members were obtained through field investigation. For every member of this
      pedigreeithe fragment containing mutational hot spots of HOXD13 was amplified by
      PCR for mutation screening. To examine whether there is any other mutation within
      coding sequence of HOXD13, exon 1 and exon 2 of HOXD13 were also amplified by
      PCR. All the amplified fragments were electrophoresed on 2% agarose gels and then
      the mutant fragments were electrophoresed on 5% polyacrylamide gels to be
      separated. Purified PCR products of normal and selected mutant alleles were
      directly sequenced. RESULTS: Comparing the HOXD13 coding sequence of the affected
      individuals with HOXD13 sequence in the GenBank and with that of the unaffected,
      an inserted segment coding 8 alanine residues within HOXD13 was found segregating
      with the disorder. This mutation is also termed polyalanine expansion. The 8
      alanine expansion can be interpreted as a reduplication of normal alanines 5-12.
      CONCLUSION: The results suggest that synpolydactyly in this kindred may be caused
      by polyalanine expansion in HOXD13.

PMID- 15952116
TI  - Interaction between maternal periconceptional supplementation of folic acid and
      reduced folate carrier gene polymorphism of neural tube defects.
AB  - OBJECTIVE: To search the interaction between reduced folate carrier gene (RFC1
      A80G) polymorphism of children with neural tube defects (NTDs) and maternal
      periconceptional no supplementation of folic acid. The purpose is to provide the
      epidemiological evidence for finding genetic marker of NTDs. METHODS: RFC1 (A80G)
      genotype was detected using PCR-restricted fragment length polymorphism for the
      blood DNA of 104 trios with NTDs-affected child, and 100 control families with
      non-malformed control children. The authors investigated the gene-environment
      interactions between the offspring RFC1 genotype and maternal periconceptional
      folic acid supplementation through a case-control study. RESULTS: It was observed
      that the offspring with the GG genotype were associated with a 2.56-fold
      increased risk of NTDs when compared to those with the AA genotype (OR = 2.56;
      95% CI = 1.04-6.36) in this population under investigation. The risk of mothers
      who did not take folic acid for having an NTDs-affected infants was 7.69 (95% CI
      = 2.86-21.75). Among the mothers who did not utilize folic acid supplements, the
      NTDs risk was 3.30 (95% CI = 1.15-9.65) for offspring with the GG genotype,
      compared to the reference (AA) genotype. Children who had the GG genotype and
      whose mothers did not take folic acid had an elevated risk for NTDs (OR = 8.80,
      95% CI = 2.86 - 29.82), compared to "offspring with AA or GA genotype" and
      "maternal folic acid use", the interactive coefficient being 1.45. CONCLUSION:
      The above findings indicate that the RFC1 genotype (GG) is a possible susceptible
      gene marker for an increased NTDs risk in Chinese population, and there is a
      potential gene-nutrient interaction between offspring RFC1 GG genotype and
      maternal periconceptional intake of folic acid on the risk of NTDs. However,the
      sample size of this study was limited, a larger sample of population-based study
      is required to pursue the initial observation.

PMID- 15952117
TI  - [Identification and sequence analysis of a novel HLA-B*5614 allele].
AB  - OBJECTIVE: To investigate the molecular genetics basis for a novel HLA allele,
      HLA-B*5614, in Chinese population. METHODS: DNA was extracted from whole blood by
      salting-out method. The HLA-B exons 2-4 of the proband was amplified and the
      amplified product was cloned using TOPO cloning sequencing kit to split the two
      alleles apart. Both strands of exons 2,3 and 4 of chosen colonies were
      sequencing. The PCR-SSP was performed to confirm the mutations detected by
      sequencing. RESULTS: The sequencing results showed the HLA-B alleles of the
      proband as B*1502 and the novel allele. The sequences of the novel allele have
      been submitted to GenBank (AY601726, AY610727, AY610728). After BLAST analysis,
      the novel allele differs from B*5608 by a single nucleotide at position 277G-->C
      in exon 2. This results in an amino acid change from Gly to Arg at codon 93.
      CONCLUSION: This allele is a novel allele and has been officially named B*5614 by
      the WHO Nomenclature Committee.

PMID- 15952118
TI  - Rapid diagnosis of spinal muscular atrophy using denaturing high-performance
      liquid chromatography.
AB  - OBJECTIVE: To introduce the application of denaturing high-performance liquid
      chromatography (DHPLC) in the diagnosis of childhood type spinal muscular atrophy
      (SMA). METHODS: Exon 7 and flanking area of survival motor neuron (SMN) gene were
      amplified by PCR in 1 standard sample, 25 normal individuals and 25 patients with
      SMA. The PCR products were then directly loaded onto the DHPLC system after
      denaturing and annealing. Different DNA segments were separated by changing the
      concentration of buffer A relative to that of buffer B. RESULTS: Different DNA
      segments were separable on the DHPLC chromatogram. Three peaks including
      SMN1/SMN2 heteroduplex peak, SMN2 homoduplex peak and SMN1 homoduplex peak were
      detected in 23 out of 25 normal individuals. Only SMN1 homoduplex peak was
      detected in 2 normal individuals and the standard sample, indicating the deletion
      of SMN2 On the contrary, only the SMN2 homoduplex peak was detected in 22 out of
      25 patients with SMA, indicating deletion of SMN1. The three peaks as those of
      normal individuals were detected in the other 3 patients, indicating no SMN1 or
      SMN2 deletion. CONCLUSION: As a new technology for diagnosing SMA, DHPLC is
      sensitive, accurate, rapid and convenient.

PMID- 15952119
TI  - Application of restriction fragment differential display-polymerase chain
      reaction in study on differential expression profiles of human diseases.
AB  - OBJECTIVE: To establish the restriction fragment differential display-polymerase
      chain reaction (RFDD-PCR) as an efficient technique for constructing and studying
      the gene expression profile of human tissues. METHODS: The tissues of mamma
      adenocarcinoma (T), cancerometastasis lymph node (L) and normal mammary (N) from
      one mammary infiltrating ductal carcinoma case were collected, and the gene
      expression profile of each kind of tissue was constructed using RFDD-PCR
      technique at equal pace according to the operating manual of Qbio-gene Company.
      Then all fragments of the three gene expression profiles were separated and
      displayed by electrophoresis. With the use of gene database at the website
      http://www.Qbio-gene.com/display, the authors identified the names of the
      probable fragments by bioinformatics analysis. Through comparison of the three
      profiles, the numbers and types of most differentially expressed gene fragments
      were displayed. RESULTS: The expression profiles of the three kinds of tissue
      have been constructed covering 1716 fragments of mammary adenocarcinoma, 1769 of
      cancerometastasis lymph nodes and 1922 of normal mammary tissue. Among these 5407
      fragments, 39.39% were exactly the same. While 33.9% sequences of T and L showed
      differences in abundance or presence, 40.9% of T and N and 39.6% fragments of L
      and N were observed differentially expressed. These differentially expressed gene
      fragments were found to relate with metastasis, differentiation, inflammation and
      so on. CONCLUSION: RFDD-PCR is an efficient technique for research in human
      diseases genomics as a mass screening for complete gene expression profile with
      high-flux. Through comparison among three or more profiles, the screening for
      candidate genes of a certain disease can be accomplished, and there is probably a
      chance to identify novel gene or expressed sequence tag.

PMID- 15952120
TI  - [Association between insulin resistance and cholesteryl ester transfer protein
      gene polymorphism in type 2 diabetes mellitus].
AB  - OBJECTIVE: To study the association between cholesteryl ester transfer protein
      (CETP) gene polymorphism and insulin resistance in type 2 diabetes. METHODS: CETP
      TaqIB gene was genotyped with polymerase chain reaction-restriction enzyme
      fragment polymorphism analysis in 108 patients with type 2 diabetes and in 60
      normal controls. Plasma lipids, fasting insulin, insulin sensitivity index and
      insulin resistance index were determined in 108 patients with type 2 diabetes.
      RESULTS: The distribution of CETP-TaqIB genotypes and B1B2 allele frequency in
      the patients with type 2 diabetes were similar to that in general population.
      High density lipoprotein cholesterol (HDL-C), apolipoprotein A1(apoA1) and
      insulin sensitivity index (ISI) levels were significantly higher in B2B2 genotype
      than in B1B1 genotype. Fasting insulin (FINS) and Homeostasis model assessment
      insulin resistance (HOMA-IR) levels were significantly lower in B2B2 genotype
      than in B1B1 genotype. No significant differences in triglyceride (TG), total
      cholesterol(TC),low density lipoprotein cholesterol (LDL-C), apolipoprotein B
      (apoB) levels were observed among different CETP-TaqIB genotype groups. By
      multivariate analysis, the determinants of ISI and HOMA-IR were body mass index
      (BMI), TC, HDL-C and CETP-TaqIB genotype. CONCLUSION: The CETP-TaqIB genotype is
      independently associated with insulin resistance and lipid metabolism. It may be
      an important risk factor of insulin resistance in type 2 diabetes.

PMID- 15952121
TI  - [Molecular cytogenetic analysis for a familial complex chromosomal
      rearrangement].
AB  - OBJECTIVE: To determine a complex chromosomal rearrangement by advanced molecular
      cytogenetic techniques and analyze its clinical effect. METHODS: A complex
      chromosomal rearrangement (CCR) involved in chromosomes 5, 16 and 20 in a 29-year
      old male carrier was determined by chromosomal microdissection and multicolor
      fluorescence in situ hybridization (M-FISH), and family degree investigation was
      further performed. RESULTS: The karyotype of the case was a complex chromosomal
      translocation among chromosomes 5, 20 and 16, and accompanied with a band of
      chromosome 20 inserted into chromosome 5. His mother and sister both had the same
      abnormal karyotype by familial investigation. CONCLUSION: The combined use of M
      FISH and chromosome microdissection is a powerful tool to determine CCR. The
      complex chromosomal rearrangement could be transmitted stably in the family, but
      still the carriers could give birth to a healthy baby by chance.

PMID- 15952122
TI  - [Intercellular adhesion molecule-1 gene K469E polymorphism and genetic
      susceptibility of ischemic stroke in Chinese Zhuang populations].
AB  - OBJECTIVE: To examine the relationship between intercellular adhesion molecule-1
      (ICAM-1) gene polymorphism and ischemic stroke (IS) in Chinese Zhuang
      populations. METHODS: The K469E polymorphism in the exon 6 of ICAM-1 gene was
      detected by polymerase chain reaction-restriction fragment length polymorphism
      analysis and DNA sequencing in 205 patients with IS of Zhuang nationality and in
      210 healthy controls, and the serum level of ICAM-1 was determined by enzyme
      linked immunosorbent assay. RESULTS: The IS group showed significantly higher
      serum levels of ICAM-1 than did the control group (P < 0.01). There was
      significant difference in frequencies of allele and genotype in K469E
      polymorphism between IS and control groups, respectively (P < 0.05). The K allele
      carriers had 1.424 times the risk of suffering from IS as compared with the E
      allele carriers (OR = 1.424, 95% CI: 1.071 - 1.894); the serum ICAM-1 level of E
      allele carriers was significantly higher than that of K allele carriers (501.24
      +/- 139.56 ng/ml vs 475.17 +/- 118.35 ng/ml, P < 0.01). CONCLUSION: There is an
      association between ICAM-1 gene K469E polymorphism and IS, and E allele may be a
      genetic risk factor of IS among Guangxi Zhuangs, in which the ICAM-1 E allele
      carriers may have up-regulated expression of ICAM-1 and hence are at a higher
      risk of ischemic stroke.

PMID- 15952123
TI  - [Polymorphism of short tandem repeat of exon 5 of MHC class-I chain related gene
      A and association with nasopharyngeal carcinoma in a southern Chinese
      population].
AB  - OBJECTIVE: To explore the association between the short tandem repeat
      polymorphism of exon 5 of MICA gene (MICA-STR) and nasopharyngeal carcinoma (NPC)
      in a southern Chinese population. METHODS: One hundred and twenty-seven
      consecutive NPC patients and 112 randomly selected normal controls residing in
      southern China mainland were analyzed for MICA-STR allelic variation and MICA
      gene deletion by fluorescent polymerase chain reaction-gene scanning and
      polymerase chain reaction-sequence specific priming. RESULTS: MICA*A9 was
      observed at significantly higher frequency in the NPC patient group than in the
      control group (relative risk = 2.524, P = 0.001,Pc = 0.006); whereas MICA*A5.1
      was present at significantly lower frequency in the NPC patient group than in the
      control group (RR = 0.418, P = 0.0004, Pc = 0.0026). Further analysis revealed
      that MICA*A9 was over-represented in male NPC patients, compared with male
      controls (RR = 3.23, P = 0.00095, Pc = 0.006); whereas MICA*A5.1 was present at
      significantly lower frequency in male NPC patients, compared with male controls
      (RR = 0.372, P = 0.0007, Pc = 0.004). None of the MICA-STR variants showed
      statistically significant frequency difference between female NPC patients and
      female controls (Pc > 0.05). CONCLUSION: MICA-STR polymorphism is associated with
      NPC, and MICA*A9 is a genetic susceptibility marker of male individuals for NPC
      in a southern Chinese population.

PMID- 15952124
TI  - [Study of relations between matrix metalloproteinase-9 polymorphism (C-1562T) and
      acute coronary syndrome in Han population of China].
AB  - OBJECTIVE: To investigate the association between acute coronary syndrome (ACS)
      and functional matrix metalloproteinase-9 polymorphism (C-1562-T). METHODS: This
      study was conducted with a case-control design including 101 patients with
      angiographically documented ACS and 105 control subjects who were free from
      coronary artery disease and had normal angiograms. Genotype was determined by
      polymerase chain reaction-restriction fragment length polymorphism for the common
      C-1562-T functional promoter polymorphism of the MMP-9 gene.The relationship
      between the polymorphism in the MMP-9 gene and the severity of coronary arterial
      stenosis was analyzed. RESULTS: The results of individual polymorphisms analysis
      showed that the frequency of C/T and T/T genotypes of the C-1562-T polymorphism
      (27.2%) in patients with ACS was significantly higher than that in those with a
      normal angiogram (13.34%).The frequencies of -1562T allele were 14.9% and 7.2% in
      ACS group and control group respectively (Chi2 = 5.617, P = 0.018). The
      frequencies of C/T and T/T genotypes of the C-1562-T polymorphism were not
      statistically different among ACS patients with normal and one,two,three or more
      significantly diseased vessels (Chi2 = 0.601, P = 0.896). CONCLUSION: The present
      findings suggest that the genetic polymorphism in MMP-9 promoter (C-1562-T) is
      associated with the susceptibility to ACS in the Han population of China. And the
      C-1562-T polymorphism may not be useful as a predictor of the severity of
      coronary atherosclerosis.

PMID- 15952125
TI  - [Application of fluorescence in situ hybridization to prenatal diagnosis of Down
      syndrome].
AB  - OBJECTIVE: Fluorescence in situ hybridization (FISH) was performed with specific
      probes to make the rapid prenatal diagnosis of Down syndrome. METHODS: FISH was
      performed respectively with locus-specific probe (LSI) 21 and centromeric probe
      (CEP) X/Y on the uncultured amniotic fluid samplesiand the cultured samples were
      analyzed by traditional cytogenetics to find the concordance rate between FISH
      and standard cytogenetics. RESULTS: Amniocentesis was performed in 23 pregnant
      women. Two samples were discarded because of contamination by maternal blood; one
      case of culture failed. A typical trisomy 21 found by FISH was in accordance with
      the result of traditional cytogenetics. A case with abnormal karyotype (X/XY)
      found by CEPX/Y probe was proved to be normal (46, XY) by cytogenetics. So the
      concordance rate was 95% (19/20). CONCLUSION: FISH is a rapid and reliable method
      to detect Down syndrome in uncultured amniotic fluid.

PMID- 15952126
TI  - [Polymorphisms within the interferon-Gamma receptor associated with systemic
      lupus erythematosus].
AB  - OBJECTIVE: To assess the association between polymorphisms within the interferon
      Gamma receptor gene(IFN-GammaR) and systemic lupus erythematosus (SLE) in Chinese
      people. METHODS: The IFN-GammaR genotypes of 94 SLE patients and 80 healthy
      subjects were examined by the reverse transcription-polymerase chain reaction (RT
      PCR)-single-strand conformation polymorphism (SSCP) method, RT-PCR-restriction
      fragment length polymorphism (RFLP) method and DNA sequencing. RESULTS: There was
      no statistically significant difference in the IFN-GammaR genotype frequencies
      between the two groups. The IFN-Gamma R2 Arg64/Arg64 genotype decreased the risk
      of SLE (OR = 2.481, 95% CI 0.992 - 6.203, P = 0.047). The decreased risk of the
      development of SLE was detected in the individuals who had the combination of IFN
      GammaR2 Arg64/Arg64 genotype and IFN-GammaR1 Val14/Val14 genotype (OR = 2.481,
      95% CI 0.992 - 6.203, P = 0.047). CONCLUSION: The IFN-GammaR2 Arg64/Arg64
      genotype does not determine susceptibility to SLE in Chinese people, and the
      combination of IFN-Gamma R2 Arg64/Arg64 genotype and IFN-Gamma R1 Val14/Val14
      genotype does not, either.

PMID- 15952127
TI  - [Genomic abnormalities detected by panel fluorescence in situ hybridization in
      chronic lymphocytic leukaemia].
AB  - OBJECTIVE: To investigate the value of panel fluorescence in situ hybridization
      for detection of genomic aberrations in chronic lymphocytic leukemia(CLL).
      METHODS: Five types of fluorescein-labelled DNA probes including centromeric
      probes for chromosomes 3,12 and 18, and two sequence-specific probes D13S272 for
      13q14.3 and ATM for 11q23 were used to perform fluorescence in situ hybridization
      (FISH) assays in 22 patients with CLL. Its results were compared with that of
      conventional cytogenetic (CC) examination in order to ascertain which method is
      more sensitive and reliable for the detection of chromosomal and genomic
      abnormalities in CLL. RESULTS: On CC examination, only 8 cases (36.3%) were found
      to have chromosomal abnormalities including sole trisomy 12 in 3 cases,
      simultaneous trisomies 3 and 12 in one case, simultaneous trisomies 3, 12 and 18
      in one case, translocation between chromosomes 5 and 15 in one case, deletion of
      13q14.3 in one case, 3q- and 18p+ in one case, 4q+ and 13q- in one case, whereas
      on panel FISH assay, 15 cases (68.1%) were found to have genomic aberrations
      including trisomy 3 in 4 cases, trisomy 12 in 6 cases, trisomy 18 in one case,
      deletion of 13q14.3 in 8 cases, deletion of 11q23 in 6 cases. CONCLUSION: Panel
      FISH is a useful method for detection of genomic aberration in CLL, if combined
      with CC, it can obviously enhance the detection rate of chromosomal abnormalities
      in CLL.

PMID- 15952128
TI  - [Association analysis on the polymorphisms of PCOL2 and Sp1 binding sites of
      COL1A1 gene and the congenital dislocation of the hip in Chinese population].
AB  - OBJECTIVE: To investigate the polymorphism distribution of the PCOL2 and Sp1
      binding sites of the collagen type I alpha 1(COL1A1) gene in Chinese population
      and explore their relationship with congenital dislocation of the hip (CDH).
      METHODS: The PCOL2 polymorphism (-1997 G/T) in COL1A1 promoter and the Sp1
      polymorphism (1546 G/T) in intron 1 were genotyped in 243 members from 81 CDH
      nuclear family trios by the technique of polymerase chain reaction-restriction
      fragment length polymorphism, and then transmission disequilibrium test was used
      to analyze the data of genotypes. RESULTS: No statistically significant
      association was observed between CDH and PCOL2 polymorphism. Significant
      differences of genotype and allele frequency distributions were detected between
      the Chinese population and the Caucasian population in Spain, and between the
      Chinese population and the Caucasian population in America. The allele at the Sp1
      site that has been found to be polymorphic in other populations was not found in
      Chinese. CONCLUSION: There exists racial difference in the distribution of the
      PCOL2 and Sp1 polymorphisms of COL1A1 gene. The results suggest that the PCOL2
      and Sp1 polymorphisms may not be the major susceptibility gene of CDH in Chinese
      population.

PMID- 15952129
TI  - [Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene
      and 5,10-methylenetetrahydrofolate reductase gene with recurrent early
      spontaneous abortion].
AB  - OBJECTIVE: To explore the relationship of plasminogen activator inhibitor-1 (PAI
      1) gene-675 4G/5G and methylenetetrahydrofolate reductase(MTHFR) gene C677T
      polymorphisms to recurrent early spontaneous abortion(RESA). METHODS: One hundred
      and twenty-seven currently non-pregnant women with at least 3 unexplained
      spontaneous abortions during the first trimester of pregnancy (patient group).
      Normal control group consisted of 117 currently non-pregnant women with at least
      1 pregnancy and without a history of prematurity, miscarriage, stillbirth,
      eclampsia and other pregnancy complications. The genotypes of PAI-1 gene and
      MTHFR gene were assessed by polymerase chain reaction-restrictive fragment length
      polymorphism. RESULTS: The frequencies of 4G/4G genotype and 4G allele of PAI-1
      were higher in patient group (45.7% and 66.1%) than in normal controls (17.1% and
      46.6%) (P < 0.01). The PAI-1 4G/4G genotype was significantly associated with
      RESA (OR = 4.8, 95% CI: 2.23 - 10.35). Besides, MTHFR gene T/T genotype and T
      allele frequencies were increased in RESA patients (43.3% and 66.5%) versus
      normal controls (21.4% and 52.6%) (P < 0.01). The patients carrying T/T genotype
      had a high risk of early spontaneous abortion (OR = 3.2, 95% CI: 1.40 - 7.30). In
      additionithe presence of the PAI-1 gene 4G/4G genotype together with the T/T
      genotype of the MTHFR gene was found to be a risk factor (OR = 6.20, 95% CI: 2.62
      - 14.67) for RESA greater than the 4G/4G genotype or the T/T genotype alone.
      CONCLUSION: The above findings suggest that genetic polymorphisms of PAI-1 4G/5G
      and MTHFR C677T were associated with RESA. They may have synergetic impact and
      present gene dosage effect on the susceptibility to the development of early
      spontaneous abortion.

PMID- 15952130
TI  - [Clinical features and the mutation of Leber's hereditary optic neuropathy in
      Chinese patients].
AB  - OBJECTIVE: To analyze the mutation of Leber's hereditary optic neuropathy (LHON)
      and the clinical features in Chinese patients. METHODS: The primary mtDNA
      mutations (3460A, 11778A and 14484C) of 156 patients (110 probands and 46
      maternal relatives with LHON) were detected by mutation-specific priming
      polymerase chain reaction, heteroduplex-single strand conformation polymorphism
      polymerase chain reaction, restriction fragment length polymorphisms and
      measurement of DNA sequence. The clinical features were analyzed by retrospective
      study. RESULTS: The 11778A mutation was found in 100 probands (90.9%), the 3460A
      mutation was found in 2 (1.8%), and the 14484C was found in 8 (7.3%) of the 110
      probands. The visual acuity at onset of the disease was 0.01 or worse in 44
      (17.6%) of 250 eyes with the 11778A mutation, but in none of 79 eyes with the
      14484C mutation. The visual acuity was 0.1 or better in 76 (29.6%) of 250 eyes
      with the 11778A mutation, but in 49 (87.3%) of 56 eyes with the 14484C mutation.
      And 6.8% of 250 eyes with the 11778A mutation recovered a mean final visual
      acuity of 0.03, whereas 50% of 56 eyes with the 14484C mutation recovered a mean
      final visual acuity of 0.8. CONCLUSION: In Chinese LHON patients the 11778A,
      14484C primary mutations are common. The clinical features are associated with
      the site of primary mutation. The visual acuity at onset of the disease and the
      visual recovery of the eyes with 14484C mutation were better than the eyes with
      the 11778A mutation.

PMID- 15952131
TI  - [Gene frequencies and haplotypes of nine Y-short tandem repeat loci in four
      minority populations of China].
AB  - OBJECTIVE: To investigate the polymorphism of nine Y-short tandem repeat loci in
      117 male individuals from four minority populations of China, and to obtain the
      polymorphism information in these populations. METHODS: Nine loci in all samples
      were amplified by PCR. Products were electrophoresed on ABI PRISM 377 DNA
      sequencer. The electrophoresis result was analyzed by Genotyper 2.0 software.
      Allele frequencies, diversities and genetic distance were calculated. RESULTS:
      Forty-three alleles and 32 haplotypes were found in Manchu population, 43 alleles
      and 33 haplotypes in Uygur population, 31 alleles and 15 haplotypes in Kirgiz
      population and 34 alleles and 23 haplotypes in Zhuang population. The closest
      genetic distance is 0.02530 between Manchu and Uygur, the highest genetic
      distance is 0.34590 between Kirgiz and Zhuang. CONCLUSION: High haplotype
      diversities were found in four populations. The study of genetic diversity among
      different populations is useful in research of their origins, migrations and
      their relationships.

PMID- 15952132
TI  - [Frequency of prothrombin gene G20210A variant in the 3'-untranslated region in
      Zhuang ethnic Chinese].
AB  - OBJECTIVE: To ascertain the frequency of prothrombin (FII) gene 3'-untranslated
      region (3'-UT) G20210A variant and to explore whether this mutation is related to
      arterial thrombosis in Chinese Zhuang population. METHODS: Seventy-six patients
      with cerebral thrombosis, 23 patients with myocardial infarction and 106 healthy
      Chinese Zhuang persons were studied. The G20210A mutant allele of the prothrombin
      gene in all blood specimens was investigated by DNA extraction, polymerase chain
      reaction amplification, Hind III digestion and polyacrylamide gel
      electrophoresis. RESULTS: The patients and normal control subjects were all
      homozygous for the normal G20210G allele, and there was no FII G20210A variant.
      CONCLUSION: Factor II gene 3'-UT G20210A mutant allele is absent in the 99
      Chinese Zhuang ethnic patients with ischemic stroke and myocardial infarction and
      is absent in 106 normal healthy Zhuang people. FII G20210A mutation may not be a
      major risk factor for thrombogenesis in ethnic Chinese.

PMID- 15952133
TI  - [Determination of HLA-A, B, and DRB1 gene polymorphism in Monba ethnic group of
      Xizang Autonomous Region, China].
AB  - OBJECTIVE: To investigate the HLA-A, B, DRB1 allele polymorphism in Monba ethnic
      population of Xizang Autonomous Region. METHODS: HLA-A, B, DRB1, DNA types in 47
      unrelated Monba ethnic healthy individuals from the Xizang Autonomous Region of
      China were analyzed by polymerase chain reaction-based reverse line-strip
      sequence specific oligonucleotide hybridization. Based on the HLA-DRB1 alleles
      frequencies of 11 other ethnic groups in China, a molecular phylogenetic tree was
      constructed by the Neighbor-Joining (NJ) method. RESULTS: Twenty-three alleles
      were detected for HLA-A, 39 for HLA-B, and 33 for HLA-DRB1. HLA-A*1101, A*2402,
      A*02011, A*0206, HLA-B*3802, B*4001, B*4002, B*51011, HLA-DRB1*12021, DRB1*0403,
      DRB1*0701, DRB1*1201 were the most common alleles. The most frequent alleles were
      HLA-A*1101(0.2128), HLA-B*3802(0.1064), and HLA-DRB1*12021(0.0851). CONCLUSION:
      The HLA loci are highly polymorphic in Monba population of Xizang Autonomous
      Region. Compared with other ethnic groups in China, the Monba ethnic group is
      close to Tibetan ethnic group.

PMID- 15952134
TI  - [Genetic polymorphisms of the CYP450 1A1, CYP450 2E1, GSTM1, GSTT1, and GSTP1 in
      Korean].
AB  - OBJECTIVE: This is an investigation on the polymorphism distribution of genes
      related with metabolism, such as cytochrome P450 1A1 (CYP1A1), CYP2E1,
      glutathione S-transferase M1 (GSTM1), GSTT1 and GSTP1 among the Korean public.
      METHODS: The techniques of polymerase chain reaction-restriction fragment length
      polymorphism were adopted. The authors analyzed the polymorphisms for 3-flanking
      region of CYP1A1 gene by the restriction endonuclease MspI, for 5-flanking region
      of the gene of CYP2E1 by PstI, for GSTP1 by BsmAI, and for the presence of GSTM1
      and GSTT1 genotype to evaluate the gene types and calculate their frequencies in
      300 healthy university students. RESULTS: The CYP1A1 genotype frequencies for
      types of m1/m1, m1/m2, and m2/m2 are 39.7%, 49.7%, and 10.7% respectively, with
      the allele frequencies 0.645 for m1 and 0.355 for m2. The CYP2E1 genotype
      frequencies are 66.7% for type of c1/c1, 30% for type of c1/c2, 3.3% for type of
      c2/c2 with the allele frequencies 0.818 for C1 and 0.182 for C2. The null type
      frequency is 53.3% for gene GSTM1 and 54.7% for gene GSTT1. The genotype
      frequencies of GSTP1 is 62% for the type of Ile/Ile, 34.3% for the type of
      Ile/Val, 3.7% for the type of Val/Val, and the allele frequencies are 0.792 for
      IIe and 0.208 for Val. All of the gene distribution matched the equilibrium law
      of Hardy-Weinberg. CONCLUSION: The genetic distribution of the genes in Korean is
      similar to the distribution of those in Chinese; more than half of the Korean in
      the study sample lack GSTM1 and GSTT1; the frequency for GSTM1 and GSTT1 null
      type of Korean is 3 times that of Indian.

PMID- 15952135
TI  - Rigidified tripodal chiral ligands in the asymmetric recognition of amino
      compounds.
AB  - Chiral rigidified piperidine and quinuclidine analogues of tris(2
      pyridylmethyl)amine (TPA) derivatives were examined for asymmetric recognition of
      amino compounds by cyclic voltammetry and fluorescence. A Cu(II) complex of a
      piperidine analogue discriminated the enantiomers of some chiral amines and amino
      alcohols, giving differences in electrochemical potential for diastereomeric
      complexes. Protonated piperidine and quinuclidine analogues were able to
      differentiate the two enantiomers of certain amino alcohols by fluorescence
      spectroscopy. The quinuclidine analogue gave a 3-fold difference in response to
      the two enantiomers of phenyglycinol.

PMID- 15952136
TI  - Lysine-based peptide nucleic acids (PNAs) with strong chiral constraint: control
      of helix handedness and DNA binding by chirality.
AB  - Two enantiomeric chiral PNAs bearing three adjacent D- or L-lysine-based residues
      in the middle of the strand ("chiral box" PNAs, sequence H
      GTAGA(Lys)T(Lys)C(Lys)ACT-NH2) have been used as models in order to
      comprehensively study the effects of the stereogenic centers on PNA conformation
      and on PNA binding properties to complementary PNA and DNA strands. The binding
      properties of the two enantiomeric PNAs and of their homologous achiral PNA have
      been extensively studied by UV and CD spectroscopy and by mass spectrometry, both
      in the antiparallel and in the parallel mode with complementary PNA and DNA
      strands. In the antiparallel PNA:PNA duplexes, L-Lys PNA were found to form left
      handed, and D-Lys PNA right handed helices, while in parallel duplexes, the
      reversed helicities were observed. Correspondingly, the preferred mode of binding
      and the best mismatch recognition of the D-Lys containing PNA with (right handed)
      DNA was found to be in the antiparallel orientation, while that of L-Lys PNA was
      found to be in the parallel mode. A rationale which correlates the preferred
      handedness of the PNA-PNA duplexes to the directionality of the binding to
      complementary DNA duplexes has been devised according to structural data and
      considering the "retro-inverso" concept widely used for peptides.

PMID- 15952137
TI  - Contributions to the theory and practice of the chromatographic separation of
      enantiomers.
AB  - The theory and practice of enantioselective capillary chromatography employing
      metal coordination compounds and modified cyclodextrins as chiral stationary
      phases are treated. A unified approach involving all contemporary chromatographic
      methods and a single enantioselective column is described. Reliable thermodynamic
      data of enantioselectivity are derived by the retention-increment method. The
      existence of an isoenantioselective temperature is demonstrated. Kinetic
      enantiomerization studies are presented. The preparative-scale separation of
      enantiomers by gas chromatography with enantioselective packed columns is
      achieved. Unusual phenomena and future aspects of enantioselective chromatography
      are discussed.

PMID- 15952149
TI  - 19th American Peptide Symposium, San Diego, California, USA, June 18-23, 2005.
      Abstracts.

PMID- 15952162
TI  - Nonrandom cell-cycle timing of a somatic chromosomal translocation: The t(X;17)
      of alveolar soft-part sarcoma occurs in G2.
AB  - The cell-cycle timing of somatic chromosomal translocations in cancer remains
      poorly understood but may be relevant to their etiology and the mechanism of
      their formation. Alveolar soft-part sarcoma (ASPS) is a rare malignant soft
      tissue tumor of uncertain lineage that provides an opportunity to address this
      question. The great majority of ASPSs have relatively simple near-diploid
      karyotypes characterized by an unbalanced der(17)t(X;17)(p11.2;q25), resulting in
      nonreciprocal fusion of TFE3 with ASPSCR1 (a.k.a. ASPL), with consequent net gain
      of Xp11.2-->pter and loss of 17q25-->qter. The presence of a normal X along with
      the der(17)t(X;17) in ASPSs that occur in men has been well described in previous
      cytogenetic reports and is most readily explained by a translocation in the G2
      phase of the cell cycle. To establish whether formation in G2 is a general
      feature of the t(X;17), we examined polymorphic loci in Xp11.2-->qter in ASPS
      from 9 women, including 7 with an unbalanced t(X;17). Our analysis showed that
      all 7 displayed retention of heterozygosity at all informative markers on Xp11.2-
      >qter, supporting preferential formation of the t(X;17) in the G2 phase of the
      cell cycle. Given that the two derivative chromosomes of a translocation in G2
      would be expected to segregate together half the time, the predominance of an
      unbalanced der(17)t(X;17) also raises the possibility of a selective advantage in
      ASPS cells for gain of Xp11.2-->pter or loss of 17q25.3-->qter or retention of an
      active copy of TFE3.

PMID- 15952163
TI  - Octopamine-like immunoreactivity in the honey bee and cockroach: comparable
      organization in the brain and subesophageal ganglion.
AB  - A serum raised against octopamine reveals in cockroaches and honey bees
      structurally comparable systems of perikarya and their extensive yet discrete
      systems of arborizations in neuropils. Numerous and prominent clusters of lateral
      cell bodies in the brain as well as many midline perikarya provide octopamine
      like immunoreactive processes to circumscribed regions of the subesophageal
      ganglion, antennal lobe glomeruli, optic neuropils, and neuropils of the
      protocerebrum. There is dense octopaminergic innervation in the protocerebral
      bridge and ellipsoid body of the central complex. The antennal lobes are supplied
      by at least three octopamine-immunoreactive neurons. In contrast, the mushroom
      bodies show the fewest immunoreactive elements. In Apis a single axon supplies
      sparse immunoreactive processes to the calyces' basal ring, collar, and lip. A
      diffuse arrangement of immunoreactive processes invades all zones of the mushroom
      body calyces in Periplaneta. These processes derive from an ascending axon
      ascribed to a dorsal unpaired median neuron at the maxillary segment of the
      subesophageal ganglion. In both taxa octopamine-immunoreactive processes invade
      only the gamma lobes of the mushroom bodies, omitting their other divisions. The
      present observations are discussed with respect to possible roles of octopamine
      in sensory integration and association.

PMID- 15952164
TI  - Octopamine-immunoreactive neurons in the brain and subesophageal ganglion of the
      hawkmoth Manduca sexta.
AB  - Octopamine is a neuroactive monoamine that functions as a neurohormone, a
      neuromodulator, and a neurotransmitter in many invertebrate nervous systems, but
      little is known about the distribution of octopamine in the brain. We therefore
      used a monoclonal antibody to study the distribution of octopamine-like
      immunoreactivity in the brain of the hawkmoth Manduca sexta. Immunoreactive
      processes were observed in many regions of the brain, with the distinct exception
      of the upper division of the central body. We focused our analysis on nine
      ventral unpaired median (VUM) neurons with cell bodies in the labial neuromere of
      the subesophageal ganglion. Seven of these neurons projected caudally through the
      ventral nerve cord. Two neurons projected rostrally into the brain
      (supraesophageal ganglion), and one of these was a bilateral neuron that sent
      projections to the gamma-lobe of the mushroom body and the lateral protocerebrum.
      Octopamine-immunoreactive processes from one or more cells originating in the
      subesophageal ganglion also form direct connections between the antennal lobes
      and the calyces of the mushroom bodies.

PMID- 15952165
TI  - Age-related changes in the number and structure of synapses in the lip region of
      the mushroom bodies in the ant Pheidole dentata.
AB  - Behavioral development in the worker caste of many adult ants follows a pattern
      of task transitions that contribute to the division of labor within colonies. In
      the ant Pheidole dentata, the number of tasks that minor workers attend to
      increases as they progress from brood-care activities within the nest to acts
      outside the nest such as foraging and defense. In this study we investigated
      synapse maturation in the lip region of mushroom bodies in young and old minor
      workers because of its potentially crucial role in behavioral development, task
      performance, and repertoire expansion. As minor workers aged, individual
      presynaptic boutons enlarged and acquired more synapses and vesicles, but the
      total number of synapses in the lip region did not change significantly. Glial
      cell processes occupied less of the synaptic neuropil as ants matured. These
      findings indicate an expansion and enhancement of efficacy at specific sets of
      synaptic connections between the projection interneurons and Kenyon cell
      dendrites and a commensurate loss of other connections as minor workers age and
      expand their behavioral repertoire.

PMID- 15952166
TI  - Enkephalin-immunoreactive interneurons extensively innervate sympathetic
      preganglionic neurons regulating the pelvic viscera.
AB  - Enkephalin (ENK)-immunoreactive (IR) axons occur in regions containing spinal
      autonomic neurons and endogenous opiates contribute to spinal regulation of
      bladder function. To identify possible spinal sites of opiate action, we used
      immunocytochemistry for ENK with retrograde tracing from the major pelvic
      ganglion (MPG), a key location for postganglionic neurons controlling pelvic
      viscera, with cholera toxin B subunit (CTB) or CTB-horseradish peroxidase (CTB
      HRP). We compared the relationship of ENK-IR axons with sympathetic preganglionic
      neurons (SPNs) projecting to the MPG between intact spinal cords and cords with 2
      or 11-week complete transections between thoracic segments 4 and 5. By light
      microscopy, sections of intact cord showed dense networks of ENK-IR axons
      surrounding CTB-IR SPNs in the intermediolateral cell column (IML), intercalated
      nucleus, and central autonomic area of lower thoracic and upper lumbar cord. This
      staining pattern was similar in rats with 2- or 11-week transections.
      Ultrastructurally, ENK-IR axons formed synapses on SPNs in all three autonomic
      subnuclei of intact cord. In the IML, ENK-IR varicosities contributed 52% of the
      synapses on the somata of MPG-projecting SPNs. In 2-week transected cord,
      synapses from ENK-IR axons persisted on SPNs and the proportion of input to IML
      SPNs had increased to 67%, probably reflecting loss of supraspinal input. These
      results suggest that endogenous opioids could play a major role in controlling
      sympathetic outflow to the bladder through a direct action on SPNs. The
      persistence of the dense ENK innervation after complete cord transection
      indicates that the ENK-IR input to SPNs arises predominantly from intraspinal
      sources.

PMID- 15952167
TI  - How can teleostean inner ear hair cells maintain the proper association with the
      accreting otolith?
AB  - The perception of equilibrium and sound in fish depends on the deflection of hair
      bundles of hair cell by the otolith. However, the accreting nature of teleostean
      otoliths poses a problem for maintenance of proper contact between the hair
      bundle and the otolith surface. Immunocytochemical staining localizes abundant
      proton-secreting H(+)-ATPase in the apical membrane of the hair cells. The H(+)
      ATPase-mediated proton secretion into the endolymph causes an approximately 0.4
      unit pH decrease, which was quantified by an H(+)-selective microelectrode. Thus,
      the hair cells maintain the proper distance from the otolith by neutralizing the
      alkaline endolymph to retard CaCO(3) deposition on the otolith opposite the
      sensory macula. Carbonic anhydrase, which hydrolyses CO(2) and produces HCO(3) (
      ) and H(+), was also localized in the hair cells. Ionocytes showed prominent
      immunostaining of carbonic anhydrase and Na(+)-K(+)-ATPase, indicating its role
      in transepithelial transport of HCO(3) (-) across the membranous labyrinth into
      the endolymph. Ionocytes form a ring closely surrounding the sensory macula.
      HCO(3) (-) secreted from the ionocytes may serve as a barrier to neutralize H(+)
      diffused from the sensory macula while keeping the endolymph alkaline outside the
      sensory macula. The ingenious arrangement of ionocytes and hair cells results in
      a unique sculptured groove, which is a common feature on the proximal surface of
      all teleostean otoliths.

PMID- 15952168
TI  - Neuronal activation related to auditory perception in the brain of a non
      songbird, the ring dove.
AB  - In songbirds, parrots, and hummingbirds, which need to learn their songs,
      exposure to conspecific song leads to increased expression of the immediate early
      gene (IEG) ZENK in a number of forebrain regions, including the caudomedial
      nidopallium (NCM) and the caudomedial mesopallium (CMM). Here we investigated the
      pattern of IEG expression in response to auditory stimulation in the brain of the
      ring dove (Streptopelia risoria), a non-songbird that does not need to learn its
      vocalizations. Ring dove males were exposed to conspecific vocalizations (coos),
      to heterospecific vocalizations (zebra finch song) or they were kept in silence.
      IEG expression was investigated by means of immunocytochemical analysis of the
      distribution of the ZENK protein product Zenk. In all three groups there was Zenk
      expression in several forebrain regions including the NCM and the CMM, similar to
      earlier findings in song-learning species. Quantitative analysis of the NCM, the
      CMM, and the hippocampus revealed significantly greater Zenk expression in birds
      exposed to conspecific vocalizations than in birds kept in silence, in the CMM
      only. These results show that there is substantial Zenk expression in the
      forebrain of a non-song-learning bird, comparable to that in avian song-learning
      taxa. These findings suggest that there is IEG expression specific to conspecific
      auditory stimulation in the CMM in both songbirds and non-songbirds.

PMID- 15952169
TI  - Identification and characterization of an aquaporin 1 immunoreactive amacrine
      type cell of the mouse retina.
AB  - Using immunocytochemistry, a type of amacrine cell that is immunoreactive for
      aquaporin 1 was identified in the mouse retina. AQP1 immunoreactivity was found
      in photoreceptor cells of the outer nuclear layer (ONL) and in a distinct type of
      amacrine cells of the inner nuclear layer (INL). AQP1-immunoreactive (IR)
      amacrine cell somata were located in the INL and their processes extended through
      strata 3 and 4 of the inner plexiform layer (IPL) with thin varicosities. The
      density of the AQP1-IR amacrine cells increased from 100/mm(2) in the peripheral
      retina to 350/mm(2) in the central retina. The AQP1-IR amacrine cells comprise
      0.5% of the total amacrine cells. The AQP1-IR amacrine cell bodies formed a
      regular mosaic, which suggested that they represent a single type of amacrine
      cell. Double labeling with AQP1 and glycine, gamma-aminobutyric acid (GABA) or
      GAD(65) antiserum demonstrated that the AQP1-IR amacrine cells expressed GABA or
      GAD(65) but not glycine. Their synaptic input was primarily from other amacrine
      cell processes. They also received synaptic inputs from a few cone bipolar cells.
      The primary synaptic targets were ganglion cells, followed by other amacrine
      cells and cone bipolar cells. In addition, gap junctions between an AQP1-IR
      amacrine process and another amacrine process were rarely observed. In summary, a
      GABAergic amacrine cell type labeled by an antibody against AQP1 was identified
      in the mouse retina and was found to play a possible role in transferring a
      certain type of visual information from other amacrine or a few cone bipolar
      cells primarily to ganglion cells.

PMID- 15952170
TI  - Proliferation, migration, neuronal differentiation, and long-term survival of new
      cells in the adult zebrafish brain.
AB  - In contrast to mammals, fish exhibit an enormous potential to produce new cells
      in the adult brain. By labeling mitotically dividing cells with 5-bromo-2'
      deoxyuridine (BrdU), we have characterized the development of these cells in the
      zebrafish (Danio rerio). Proliferation zones were located in specific regions of
      the olfactory bulb, dorsal telencephalon (including a region presumably
      homologous to the mammalian hippocampus), preoptic area, dorsal zone of the
      periventricular hypothalamus, optic tectum, torus longitudinalis, vagal lobe,
      parenchyma near the rhombencephalic ventricle, and in a region of the medulla
      oblongata lateral to the vagal motor nucleus, as well as in all three
      subdivisions of the cerebellum, the valvula cerebelli, the corpus cerebelli, and
      the lobus caudalis cerebelli. In the valvula cerebelli and the corpus cerebelli,
      the young cells migrated from their site of origin in the molecular layers to the
      corresponding granule cell layers. By contrast, in the lobus caudalis cerebelli
      and optic tectum, no indication of a migration of the newly generated cells over
      wider distances could be obtained. BrdU-labeled cells remained present in the
      brain over at least 292 days post-BrdU administration, indicating a long-term
      survival of a significant portion of the newly generated cells. The combination
      of BrdU immunohistochemistry with immunolabeling against the neural marker
      protein Hu, or with retrograde tracing, suggested a neuronal differentiation in a
      large portion of the young cells.

PMID- 15952171
TI  - Connection from cortical area V2 to V3 A in macaque monkey.
AB  - The V2 projection to V3 A was labeled by pressure microinjecting biotinylated
      dextran amine (BDA) and Phaseolus vulgaris lectin (PHA-L) into V2 just posterior
      to the lunate sulcus. Dense terminal labeling in clusters was found in layer 4,
      with a weaker terminal projection in layer 3. About 3.5--4.1% of the synapses in
      the densest bouton clusters in layer 4 were made by labeled boutons. All were
      asymmetric (Gray's type 1) synapses, made by spiny, excitatory neurons. The most
      frequently encountered synaptic targets were spines (76% in layer 4, 98% in layer
      2/3). The remainder of the synaptic targets were dendritic shafts, of which just
      less than half (44%) had the characteristic ultrastructure of smooth (inhibitory)
      cells. Multisynaptic boutons were rare (mean synapses per bouton for layer 4 1.2,
      for layer 2/3 1.1). The mean size of the postsynaptic densities found on spines
      (0.11 microm(2)) was not significantly different from that for dendrites (0.09
      microm(2)). In terms of their type, laminar location, number, and targets, the
      synapses that formed the V2 projection to V3 A are typical of a major,
      excitatory, feedforward projection of macaque visual cortex.

PMID- 15952172
TI  - Upregulation of calpain correlates with increased neurodegeneration in acute
      experimental auto-immune encephalomyelitis.
AB  - Although calpain up-regulation is well established in experimental auto-immune
      encephalomyelitis (EAE), a link between increased calpain expression and activity
      and neurodegeneration has not been examined. Therefore, spinal cord tissue from
      Lewis rats with EAE was examined to test the hypothesis that increased calpain
      expression in neurons would correlate with increased cell death and axonal damage
      in a time-dependent manner following EAE induction. We found that increased
      calpain expression in EAE corresponded to increased TUNEL-positive neurons and to
      increased expression of dephosphorylated neurofilament protein, markers of cell
      death and axonal degeneration, respectively. An increase in internucleosomal DNA
      fragmentation in EAE spinal cord suggested that cell death was, at least
      partially, due to apoptosis. Axonal damage was further demonstrated in EAE spinal
      cord compared with control via morphological analysis, revealing granular
      degeneration of filament and microtubule integrity, loss of myelin, and
      mitochondrial damage. Calcium (Ca2+) influx, which is required for calpain
      activation, was also increased in EAE spinal cord. From these findings, we
      conclude that increases in Ca2+-induced calpain activity may play a crucial role
      in neurodegeneration in acute EAE.

PMID- 15952173
TI  - Decreased FOXP3 levels in multiple sclerosis patients.
AB  - Autoimmune diseases such as multiple sclerosis (MS) may result from the failure
      of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is
      the first to establish that MS patients have abnormalities in FOXP3 message and
      protein expression levels in peripheral CD4+ CD25+ T cells (Tregs) that are
      quantitatively related to a reduction in functional suppression induced during
      suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links
      a defect in functional peripheral immunoregulation to an established genetic
      marker that has been unequivocally shown to be involved in maintaining immune
      tolerance and preventing autoimmune diseases. Diminished FOXP3 levels thus
      indicate impaired immunoregulation by Tregs that may contribute to MS. Future
      studies will evaluate the effects of therapies known to influence Treg cell
      function and FOXP3 expression, including TCR peptide vaccination and supplemental
      estrogen.

PMID- 15952174
TI  - Medium-sized peptides as built in carriers for biologically active compounds.
AB  - A growing number of oligopeptides of natural and/or synthetic origin have been
      described and considered as targeting structures for delivery bioactive compounds
      into various cell types. This review will outline the discovery of peptide
      sequences and the corresponding mid-sized oligopeptides with membrane
      translocating properties and also summarize de novo designed structures
      possessing similar features. Conjugates and chimera constructs derived from these
      sequences with covalently attached bioactive peptide, epitope, oligonucleotide,
      PNA, drug, reporter molecule will be reviewed. A brief note will refer to the
      present understanding on the uptake mechanism at the end of each section.

PMID- 15952175
TI  - Morphine-6-glucuronide: actions and mechanisms.
AB  - Morphine-6-glucuronide (M6G) appears to show equivalent analgesia to morphine but
      to have a superior side-effect profile in terms of reduced liability to induce
      nausea and vomiting and respiratory depression. The purpose of this review is to
      examine the evidence behind this statement and to identify the possible reasons
      that may contribute to the profile of M6G. The vast majority of available data
      supports the notion that both M6G and morphine mediate their effects by
      activating the micro-opioid receptor. The differences for which there is a
      reasonable consensus in the literature can be summarized as: (1) Morphine has a
      slightly higher affinity for the micro-opioid receptor than M6G, (2) M6G shows a
      slightly higher efficacy at the micro-opioid receptor, (3) M6G has a lower
      affinity for the kappa-opioid receptor than morphine, and (4) M6G has a very
      different absorption, distribution, metabolism, and excretion (ADME) profile from
      morphine. However, none of these are adequate alone to explain the clinical
      differences between M6G and morphine. The ADME differences are perhaps most
      likely to explain some of the differences but seem unlikely to be the whole
      story. Further work is required to examine further the profile of M6G, notably
      whether M6G penetrates differentially to areas of the brain involved in pain and
      those involved in nausea, vomiting, and respiratory control or whether micro
      opioid receptors in these brain areas differ in either their regulation or
      pharmacology.

PMID- 15952176
TI  - Estrogen receptor-alpha mediates estradiol attenuation of ATP-induced Ca2+
      signaling in mouse dorsal root ganglion neurons.
AB  - A mechanism underlying gender-related differences in pain perception may be
      estrogen modulation of nociceptive signaling in the peripheral nervous system. In
      rat, dorsal root ganglion (DRG) neurons express estrogen receptors (ERs) and
      estrogen rapidly attenuates ATP-induced Ca2+ signaling. To determine which
      estrogen receptor mediates rapid actions of estrogen, we showed ERalpha and
      ERbeta expression in DRG neurons from wild-type (WT) female mice by RT-PCR. To
      study whether ERalpha or ERbeta mediates this response, we compared estradiol
      action mediating Ca2+ signaling in DRG neurons from WT, ERalpha knockout
      (ERalphaKO), and ERbetaKO mice in vitro. ATP, an algesic agent, induced [Ca2+]i
      transients in 48% of small DRG neurons from WT mice. 17beta-Estradiol (E2)
      inhibited ATP-induced intracellular Ca2+ concentration ([Ca2+]i) with an IC50 of
      27 nM. The effect of E2 was rapid (5-min exposure) and stereo specific; 17alpha
      estradiol had no effect. E2 action was blocked by the ER antagonist ICI 182,780
      (1 microM) in WT mouse. Estradiol coupled to bovine serum albumin (E-6-BSA),
      which does not penetrate the plasma membrane, had the same effect as E2 did,
      suggesting that a membrane-associated ER mediated the response. In DRG neurons
      from ERbetaKO mice, E2 attenuated the ATP-induced [Ca2+]i flux as it did in WT
      mice, but in DRG neurons from ERalphaKO mice, E2 failed to inhibit the ATP
      induced [Ca2+]i increase. These results show that mouse DRG neurons express ERs
      and the rapid attenuation of ATP-induced [Ca2+]i signaling is mediated by
      membrane-associated ERalpha.

PMID- 15952177
TI  - Heat shock factor 1-deficient mice exhibit decreased recovery of hearing
      following noise overstimulation.
AB  - Heat shock proteins (Hsps) can enhance cell survival in response to stress. Heat
      shock factor 1 (Hsf1) is the major transcription factor that regulates stress
      inducible Hsp expression. We previously demonstrated the presence of Hsf1 in the
      rodent cochlea and also demonstrated that a heat shock known to precondition the
      cochlea against noise trauma results in Hsf1 activation in the rodent cochlea. In
      the present study, we used an Hsf1-deficient (Hsf1-/- mouse model to determine
      whether eliminating the Hsf1-dependent stress pathway would influence hearing
      loss and/or recovery from a moderate-intensity noise. Hsf1-/- mice and their
      normal littermates (Hsf1+/+) were exposed to a 98-dB, broadband (2-20 kHz) noise
      for 2 hr, and auditory brainstem response thresholds were measured at three
      frequencies (4, 12, and 20 kHz) 3 hr, 3 days, and 2 weeks after noise. Hsf1-/-
      mice had greater hearing loss than Hsf1+/+ mice, with significant differences in
      recovery observed at all frequencies tested by 2 weeks after noise. Increased
      outer hair cell loss was also observed in Hsf1-/- mice following noise. These
      studies provide evidence for the importance of Hsf1 in cochlear protection,
      recovery, and/or repair following noise overstimulation.

PMID- 15952178
TI  - Heparin-binding epidermal growth factor-like growth factor stimulates cell
      proliferation in cerebral cortical cultures through phosphatidylinositol 3'
      kinase and mitogen-activated protein kinase.
AB  - Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF)
      stimulates cell proliferation in the adult mammalian brain, but the mechanism
      involved is unknown. To address this issue we treated mouse brain cerebral
      cortical cultures enriched in neuronal precursors with full-length HB-EGF, its HB
      or EGF-like domain alone, or both domains in combination. Labeling of cultures
      with bromodeoxyuridine (BrdU), a marker of cell proliferation, was increased
      approximately 10% by the HB domain and approximately 20% by the EGF-like domain,
      and the effects of the two domains were additive. Full-length HB-EGF was most
      effective (approximately 50% increase) in stimulating BrdU incorporation.
      Preincubation with heparinase III or with Na-chlorate abolished cell
      proliferation induced by HB-EGF, consistent with dependence on cell-surface
      heparan sulfate proteoglycans. The effect of HB-EGF was also blocked by the EGF
      receptor (EGFR/ErbB1) inhibitors PD153035 and PD158780, implicating EGFR in HB
      EGF-induced cell proliferation. The phosphatidylinositol 3'-kinase (PI3K)
      inhibitors LY294002 and wortmannin, and the MAPK/extracellular signal-regulated
      kinase (ERK) kinase (MEK) inhibitors U0126 and PD98059, reduced HB-EGF-induced
      BrdU incorporation into cultures, and HB-EGF enhanced phosphorylation of Akt and
      ERK, implying a role for PI3K/Akt and MEK/ERK signaling in HB-EGF-stimulated cell
      proliferation. These findings help to clarify the molecular mechanisms through
      which HB-EGF operates.

PMID- 15952179
TI  - Factors that influence physicians' detection of distress in patients with cancer:
      can a communication skills training program improve physicians' detection?
AB  - BACKGROUND: No study to date has assessed the impact of skills acquisition after
      a communication skills training program on physicians' ability to detect distress
      in patients with cancer. METHODS: First, the authors used a randomized design to
      assess the impact, on physicians' ability to detect patients' distress, of a 1
      hour theoretical information course followed by 2 communication skills training
      programs: a 2.5-day basic training program and the same training program
      consolidated by 6 3-hour consolidation workshops. Then, contextual, patient, and
      communication variables or factors associated with physicians' detection of
      patients' distress were investigated. After they attended the basic communication
      skills training program, physicians were assigned randomly to consolidation
      workshops or to a waiting list. Interviews with a cancer patient were recorded
      before training, after consolidation workshops for the group that attended
      consolidation workshops, and approximately 5 months after basic training for the
      group that attended basic training without the consolidation workshops. Patient
      distress was recorded with the Hospital Anxiety and Depression Scale before the
      interviews. Physicians rated their patients' distress on a visual analog scale
      after the interviews. Physicians' ability to detect patients' distress was
      measured through computing differences between physicians' ratings of patients'
      distress and patients' self-reported distress. Communication skills were analyzed
      according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS:
      Fifty-eight physicians were evaluable. Repeated-measures analysis of variance
      showed no statistically significant changes over time and between groups in
      physicians' ability to assess patient distress. Mixed-effects modeling showed
      that physicians' detection of patients' distress was associated negatively with
      patients' educational level (P = 0.042) and with patients' self-reported distress
      (P < 0.000). Mixed-effects modeling also showed that physicians' detection of
      patient distress was associated positively with physicians breaking bad news (P =
      0.022) and using assessment skills (P = 0.015) and supportive skills (P = 0.045).
      CONCLUSIONS: Contrary to what was expected, no change was observed in physicians'
      ability to detect distress in patients with cancer after a communication skills
      training programs, regardless of whether physicians attended the basic training
      program or the basic training program followed by the consolidation workshops.
      The results indicated a need for further improvements in physicians' detection
      skills through specific training modules, including theoretical information about
      factors that interfere with physicians' detection and through role-playing
      exercises that focus on assessment and supportive skills that facilitate
      detection.

PMID- 15952180
TI  - Vascular endothelial growth factor receptor-1 promotes migration and invasion in
      pancreatic carcinoma cell lines.
AB  - BACKGROUND: Vascular endothelial growth factor receptor-1 (VEGFR-1) is one of
      three receptor tyrosine kinases for VEGF, a key regulator of angiogenesis in
      cancer. Although VEGFRs initially were believed to be expressed exclusively on
      endothelial cells (ECs), recent studies have demonstrated the presence of VEGFR-1
      on non-EC types. The authors hypothesized that VEGFR-1 is present and functional
      in pancreatic carcinoma cells, contributing to the malignant phenotype. METHODS:
      The authors assessed the expression of VEGFR-1 and its ligands in 11 pancreatic
      carcinoma cell lines by reverse-transcriptase-polymerase chain reaction, enzyme
      linked immunosorbent assay, and/or Western blot analysis. The function of VEGFR-1
      was evaluated by treating two representative cell lines with VEGF-B, a selective
      ligand for VEGFR-1, and/or a specific anti-VEGFR-1 antibody and assessing the
      effects on signaling, migration, invasion, and proliferation. RESULTS: All 11
      pancreatic carcinoma cell lines expressed VEGFR-1 mRNA and protein, as well as
      the VEGFR-1 ligands VEGF-A and VEGF-B. Two representative cell lines (L3.6 and
      Panc-1) exhibited VEGF-B-induced mitogen-activated protein kinase signaling. A
      VEGFR-1 neutralizing antibody abrogated signaling, confirming that the ligand
      effect was mediated through VEGFR-1. VEGFR-1 stimulation by VEGF-A or VEGF-B was
      found to promote migration in both cell lines. Panc-1 cells also demonstrated
      enhanced Matrigel invasion after VEGFR-1 stimulation. VEGFR-1-dependent migration
      and invasion were blocked by the VEGFR-1 neutralizing antibody. VEGFR-1
      activation did not appear to enhance cell proliferation. CONCLUSIONS: VEGFR-1
      appears to be expressed ubiquitously in pancreatic carcinoma cell lines, in which
      it induces signaling and promotes migration and invasion. Overexpression of VEGF
      in tumors may activate tumor cells bearing VEGFR-1 via an autocrine pathway.
      Agents targeting VEGF or its receptors may have a dual inhibitory effect on tumor
      growth by suppressing both angiogenesis and tumor cell function.

PMID- 15952182
TI  - Serum HER-2/neu conversion to positive at the time of disease progression in
      patients with breast carcinoma on hormone therapy.
AB  - BACKGROUND: Prolonged exposure of breast carcinoma cells in vitro to tamoxifen
      results in tamoxifen resistance. Tamoxifen-resistant cells express increased HER
      2/neu mRNA and protein. The objective of this study was to determine whether
      patients with metastatic or locally advanced breast carcinoma who have negative
      serum HER-2/neu status at the initiation of first-line hormone therapy with
      letrozole or tamoxifen convert to positive serum HER-2/neu status at the time of
      disease progression and to determine whether serum HER-2/neu conversion to
      positive status is associated with response to therapy and overall survival.
      METHODS: Serum samples were obtained at baseline and at the time of disease
      progression from 240 patients who initially had negative serum HER-2/neu status
      (< 15 ng/mL). A manual microtiter, enzyme-linked immunosorbent assay that was
      specific for the extracellular domain of the HER-2/neu (c-erbB-2) oncoprotein
      product was used to quantitate serum levels. RESULTS: Among 240 patients, 61
      patients (26%) converted from serum HER-2/neu negative to positive (> 15 ng/mL)
      at the time of disease progression. Thirty-two of 129 patients (25%) who were
      treated with tamoxifen and 29 of 111 patients (26%) who were treated with
      letrozole became converted to positive serum HER-2/neu status at the time of
      disease progression. The response rate and the time to disease progression on
      first-line hormone therapy were not affected by serum HER-2/neu conversion. The
      survival of patients who converted to positive serum HER-2/neu status was
      significantly shorter compared with the survival of patients who remained
      negative for serum HER-2/neu. A multivariate analysis revealed that conversion to
      positive serum HER-2/neu status was an independent prognostic variable for
      survival. CONCLUSIONS: Conversion to positive serum HER-2/neu status occurred in
      approximately 25% of patients who received first-line hormone therapy. Conversion
      to serum HER-2/neu-positive status occurred with equal frequency in antiestrogen
      and aromatase-inhibitor therapy. The current results showed that serum conversion
      to HER-2/neu-positive status was an independent risk factor for decreased
      survival in patients with breast carcinoma.

PMID- 15952183
TI  - Loss of carcinoembryonic antigen-related cell adhesion molecule 1 expression is
      an adverse prognostic factor in hepatocellular carcinoma.
AB  - BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)
      is a negative regulator of tumor cell growth, and may function as a tumor
      suppressor. CEACAM1 expression is down-regulated with increasing histologic grade
      in a number of malignancies. The authors hypothesized that loss of CEACAM1
      expression in hepatocellular carcinoma (HCC) cells may function as an adverse
      prognostic factor. METHODS: A retrospective analysis was conducted of 139
      consecutive patients who underwent resection for HCC, with a median follow-up
      period of 83 months. Immunohistochemistry of the resected specimens was conducted
      using a monoclonal anti-CEACAM1 antibody. CEACAM1 expression in HCC was
      classified into two categories: diffuse expression, characterized by positive
      staining throughout the tumor specimen, or loss of expression, in which there
      were distinct areas of negative staining within the tumor specimen. RESULTS: Of
      the 139 patients, 113 were classified as having tumors with diffuse expression
      and 26 had loss-of-expression tumors. Loss of CEACAM1 expression was more
      frequent in tumor specimens with Edmondson-Steiner Grades III or IV (21 of 32
      [66%]) than in tumor specimens with Grades I or II (5 of 107 [5%]; P < 0.001) and
      was always seen in areas with the highest histologic grade. Loss of CEACAM1
      expression was significantly associated with large tumor size, multiplicity of
      the tumor, portal vein invasion, and satellite nodules and affected survival
      adversely, according to univariate (P < 0.0001) and multivariate analyses
      (relative risk, 5.737; P < 0.001). CONCLUSIONS: Loss of CEACAM1 expression
      reflects aggressive tumor biology and thus indicates a poor prognosis for
      patients with HCC.

PMID- 15952184
TI  - An association analysis of microsatellite markers across the Prader
      Willi/Angelman critical region on chromosome 15 (q11-13) and autism spectrum
      disorder.
AB  - Autism (OMIM 209850) is a neurodevelopmental disorder with a significant genetic
      component of a complex nature. Cytogenetic abnormalities in the Prader
      Willi/Angelman syndrome critical region (PWACR) on chromosome 15 (q11-13) have
      been described in several individuals with autism. We have examined five
      microsatellite markers spread across the 4 Mb PWACR for linkage disequilibrium
      (LD) in 148 families with autism spectrum disorder (ASD) and a subset of 82
      families with autism using the extended transmission disequilibrium test (ETDT).
      The markers examined were D15S11, D15S128, D15S1506, GABRB3, and D15S1002. In
      addition we have examined the microsatellite D15S822 for hemizygous deletion
      status in our sample as it had been previously reported to be increased in
      autism. We found no significant LD with any of the markers tested either in the
      ASD or autism families when looking at paternal and maternal meioses combined.
      However, as there are known imprinted genes in the region, including possibly
      GABRB3, we also examined for LD in paternal and maternal meioses separately.
      Examining paternal transmissions only, we found marginal evidence for LD with a
      protective allele at marker D15S11 in the ASD families (Chi-sq 7 df, P = 0.05)
      and marginal evidence for risk alleles at markers D15S1506 (Chi-sq 13.7, 6 df, P
      = 0.06), GABRB3 (Chi-sq 15.9, 8 df, P = 0.11) and D15S1002 (Chi-sq 17.7, 9 df, P
      = 0.08) in the autism only families. The allele responsible for the association
      with GABRB3 is the 191 allele which was previously reported to be
      overtransmitted. Hemizygous deletion of the microsatellite D15S822 was found in 3
      out of 340 independent chromosomes in our sample; a rate of 0.8%. This is not
      significantly different to the frequency in the general population. In
      conclusion, our results did not rule out the involvement of this chromosomal
      region, but provided further evidence, albeit very limited, to implicate GABRB3.
      Further more systematic work in larger samples is required and confirmation that
      GABRB3 is imprinted is desirable.

PMID- 15952185
TI  - 5-HT 1A polymorphism and self-transcendence in mood disorders.
AB  - Recently, an association between serotonin 1A receptor binding potential and self
      transcendence scores at the temperament and character inventory (TCI) has been
      reported. We tested involvement of 5-HT(1A) gene in this trait, in a sample of 40
      remitted mood disorder patients. Subjects with the 5-HT(1A)*C/C genotype showed
      significantly lower scores at the total self-transcendence and at the sub-scales
      of transpersonal identification and spiritual acceptance. Our preliminary results
      further support the involvement of the serotoninergic pattern in the self
      transcendence character trait.

PMID- 15952186
TI  - Chick chorioallantoic membrane as an in vivo model to study vasoreactivity:
      characterization of development-dependent hyperemia induced by
      epoxyeicosatrienoic acids (EETs).
AB  - Shell-less culture of chick chorioallantoic membrane (CAM) of developing chicken
      embryos is a useful model to evaluate the effects of vascular agents. We assessed
      the response of CAM vessels to epoxyeicosatrienoic acids (EETs), derivatives of
      the essential fatty acid arachidonic acid, that have a number of important
      biological functions, including dilation of microvessels in the coronary,
      cerebral, renal, and mesenteric circulations. Three of four regioisomers of EETs,
      14,15-, 11,12-, and 8,9-EET, induced a characteristic dose-dependent acute
      hyperemia within 4 min after application on 10-day-old CAMs. This response was
      marked in early stages of development (between days 8 and 10), but the frequency
      and intensity of the response were reduced after 11 days of development.
      Histological examination demonstrated that the hyperemia was not due to
      extravasation of erythrocytes. However, many capillaries were distended and
      contained densely packed erythrocytes as compared to uniformly arranged vessels
      and erythrocytes in untreated CAMs. Transmission electron microscopy showed the
      basal laminae surrounding capillaries remained intact, similar to those in
      vehicle-treated or untreated CAM tissue. The hyperemia was specific to EETs since
      we did not observe it to be induced by other vasodilators such as nitric oxide or
      prostacyclin. In conclusion, we report a novel vascular response to EETs using
      the CAM as an in vivo model. These lipids specifically distend a subset of
      capillaries in a dose- and development-dependent manner.

PMID- 15952187
TI  - Effects of fish oil treatment on bleomycin-induced pulmonary fibrosis in mice.
AB  - Bleomycin is an antibiotic used to treat a variety of neoplasms. A major side
      effect of bleomycin therapy is the induction of an intense inflammatory response
      that develops into pulmonary fibrosis. Several studies have shown that certain
      polyunsaturated fatty acids found in fish oil reduce the inflammatory response in
      vivo. Fish oil has been employed for the treatment of several pathologies such as
      glomerulonephritis, cardiovascular diseases, rheumatoid arthritis, and even as an
      adjuvant in cancer therapy. This study examined the effects of fish oil treatment
      on the development of bleomycin-induced pulmonary fibrosis. Mice were
      intraperitoneally treated with bleomycin or with saline daily for 10 days, and 15
      days after the last injection they started to receive fish oil by gavage for 14
      days. The lungs were processed for light microscopy, biochemical and
      immunohistochemical investigations. Fish oil did not prevent the development of
      pulmonary fibrosis after the injury as shown by light microscopy, cytokines
      immunohistochemical analysis, TBARS content and protein levels in the lung. In
      addition however, fish oil itself induced a slight inflammatory process in the
      lung, as observed by the increase in cellularity, vasodilatation in the lung
      parenchyma, TBARS content, and a slight increase in the lung protein content.

PMID- 15952188
TI  - Addition of an aminopeptidase N-binding sequence to human endostatin improves
      inhibition of ovarian carcinoma growth.
AB  - BACKGROUND: Blood vessels in tumors express higher level of aminopeptidase N
      (APN) compared with normal tissues. It has been reported that peptides that
      contain asparagine-glycine-arginine (NGR) sequence home to APN in tumor
      vasculature. Increased expression of APN in tumor vascular endothelium,
      therefore, offers an opportunity to target NGR peptide-linked therapeutic
      reagents to tumors. METHODS: To determine whether an additional NGR sequence
      could improve endothelial homing and biologic activity, human endostatin was
      modified genetically to introduce an NGR motif (NGR-endostatin) and was expressed
      in yeast. In vitro biologic activity of NGR-endostatin was compared with the
      native protein in endothelial cell proliferation and migration. NGR-modified
      endostatin was used in tumor localization studies. Finally, the effects of
      endostatin and NGR-endostatin on tumor growth were determined in two model
      systems. RESULTS: Human endostatin has an internal NGR sequence, which is not
      accessible to bind APN. However, the addition of an NGR-sequence at the amino
      terminus resulted in strong binding and inhibition of endothelial cell APN. NGR
      endostatin showed increased binding to endothelial cells compared with the native
      protein. Increased binding of endostatin also coincided with improved
      antiangiogenic properties of endostatin. NGR modification improved tumor
      localization and, as a consequence, effectively inhibited ovarian carcinoma
      growth in athymic nude mice. CONCLUSIONS: These studies demonstrated that human
      endostatin can be modified genetically to improve its ability to inhibit tumor
      growth.

PMID- 15952189
TI  - Microarray versus conventional prediction of lymph node metastasis in colorectal
      carcinoma.
AB  - BACKGROUND: The authors investigated whether microarray-based gene expression
      analysis of primary tumor biopsy material could be used to predict lymph node
      status in patients with colorectal carcinoma (CRC). Lymphatic metastasis strongly
      determines treatment algorithms in CRC. Currently, postoperative histology
      results are needed to determine lymph node status. Reliable preoperative
      information would be useful to advance treatment strategies. METHODS: In
      specimens from 66 patients with CRC from the Erlangen Registry of Colorectal
      Cancer, 41 shock-frozen samples of International Union Against Cancer (UICC)
      Stage I-II CRC and 25 samples of UICC Stage III CRC were microdissected manually,
      RNA was isolated, and gene chips (HG-U133A; Affymetrix) were hybridized.
      Prediction rates for lymphatic metastasis were calculated using conventional
      clinicopathologic parameters, gene expression data, and a combination of both.
      Prediction error, specificity, and sensitivity were analyzed using six different
      statistical classifiers. RESULTS: Analysis of conventional parameters produced a
      positive prediction rate that ranged between 53% and 61%, sensitivity of 42%, and
      specificity of 72%. Microarray prediction rates were between 62% and 67% for
      lymphatic metastasis. Specificity was between 76% and 83%, and sensitivity was
      between 38% and 48%, depending on the statistical procedure. The conventional
      estimates were improved by 9-12% when array data were added. CONCLUSIONS: Current
      data show that the prediction of lymphatic metastasis can be improved by gene
      expression profiling of the primary tumor biopsy, alone or in combination with
      conventional parameters. Gene expression profiling may become valuable
      increasingly in planning treatment for patients with CRC.

PMID- 15952190
TI  - Typhlitis in childhood cancer.
AB  - BACKGROUND: Typhlitis is increasingly recognized in children undergoing
      chemotherapy but is poorly characterized. The authors investigated the
      demographic, clinical, and imaging (ultrasonography and computed tomography [CT]
      scans) variables related to the diagnosis, risk, and outcome of typhlitis.
      METHODS: The authors reviewed the records of patients who had typhlitis (bowel
      wall thickness > or = 0.3 cm plus clinical findings) during treatment at St. Jude
      Children's Research Hospital (Memphis, TN) between 1990 and 2001. They assessed
      whether duration of typhlitis was related to bowel wall thickness, extent of
      colonic involvement, ascites, demographics, primary diagnosis, symptoms of
      typhlitis, or duration of neutropenia. To identify risk factors for typhlitis,
      the authors compared the demographic data and previous drug therapy of 78
      patients who had typhlitis and 1231 identically treated children who did not.
      RESULTS: Of 3171 children, 83 (2.6%) developed typhlitis. Frequent symptoms were
      abdominal pain (91%), fever (84%), abdominal tenderness (82%), and diarrhea
      (72%). Twelve percent of the patients were not neutropenic. Duration of typhlitis
      was associated with bowel wall thickness measured by ultrasonography (n = 68; P =
      0.05) but not CT scan (n = 48; P = 0.67) and was associated with duration of
      neutropenia (P = 0.02), fever (P = 0.01), and abdominal tenderness (P = 0.04).
      Age >16 years at cancer diagnosis was the only demographic factor associated with
      typhlitis (P = 0.03). Two patients died of typhlitis. CONCLUSIONS:
      Ultrasonography was a useful imaging modality for children with suspected
      typhlitis. The classic triad of abdominal pain, fever, and neutropenia may be
      absent. The severity of typhlitis was related to the duration of neutropenia and
      the presence of fever or abdominal tenderness.

PMID- 15952191
TI  - Periconceptional vitamin useand leukemia risk in children with Down syndrome: a
      Children's Oncology Group study.
AB  - BACKGROUND: Periconceptional vitamin supplementation reduces the risk of neural
      tube defects, and possibly may reduce the risk of certain childhood malignancies,
      including acute lymphoblastic leukemia (ALL). Because children with Down syndrome
      (DS) experience a 20-fold higher risk of leukemia than the general population,
      the authors evaluated whether periconceptional vitamin supplementation reduced
      the risk of leukemia in children with DS. METHODS: From 1997 to 2002, 158
      children ages birth-18 years with DS and acute leukemia (n = 61 children with
      acute myeloid leukemia [AML] and n = 97 children with ALL) were enrolled through
      the Children's Oncology Group in North America. Children with DS alone (n = 173)
      were identified through the cases' pediatric clinics and frequency matched to
      cases on age. Mothers of cases and controls completed a telephone interview that
      included questions regarding vitamin supplement use in the periconceptional
      period and after knowledge of pregnancy. RESULTS: A decreased risk of leukemia
      was observed with vitamin supplementation in the periconceptional period (odds
      ratio [OR] = 0.63; 95% confidence interval [95% CI], 0.39-1.00). When stratified
      by leukemia type, the reduced risk was observed for ALL (OR = 0.51; 95% CI, 0.30
      0.89), but not for AML (OR = 0.92; 95% CI, 0.48-1.76). Compared with vitamin use
      in the periconceptional period, use only after knowledge of pregnancy was
      associated with an increased risk of leukemia (OR = 1.61; 95% CI, 1.00-2.58).
      This was observed for both ALL and AML. CONCLUSIONS: These data added to a
      growing body of evidence that suggests that periconceptional vitamin use may be
      protective in the development of certain childhood cancers.

PMID- 15952192
TI  - Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on
      aspiration cytology and core needle biopsy: case series and review of the
      literature.
AB  - BACKGROUND: Cholangiocarcinoma (CC) represents approximately 10% of primary liver
      malignancies and can mimic metastatic adenocarcinoma. METHODS: The authors
      retrospectively reviewed the cytopathology files at the University of Texas
      Medical Branch to identify patients who were diagnosed with intrahepatic or
      extrahepatic CC by aspiration cytology between 1995 and 2004. Brush cytology
      specimens of extrahepatic CC were excluded. All diagnoses were confirmed as CC by
      clinical, imaging, and histopathologic findings and by chart review. RESULTS:
      Cytopathology files from 13 patients with CC diagnosed by FNA were retrieved. The
      male:female ratio was 5:8, and the patients ranged in age from 29 years to 74
      years (mean age, 59 years). In 12 of 13 patients, aspirates were obtained by
      ultrasound guidance; and, in 1 patient, computed tomography guidance was used.
      Three patients had aspirates only, 10 patients also had core biopsies, and 1
      patient had cell block preparations. The phenotypic distribution of CC according
      to the World Health Organization (WHO) histologic classification was 9
      adenocarcinoma (intrahepatic), not otherwise specified (NOS) (69%); 2 gastric
      foveolar type (extrahepatic) CCs (15%); 1 intestinal type (extrahepatic) CC (8%);
      and 1 sarcomatous/spindle cell type (intrahepatic) CC (8%). One adenocarcinoma,
      NOS was well differentiated CC with bland tubular architecture, and one was
      pleomorphic. Ancillary histochemical and immunochemical stains were performed on
      5 of 13 specimens, which included 4 core biopsies and 1 aspirate with Mucicarmine
      positivity (3 specimens), carcinoembryonic antigen positivity (3 specimens), and
      a cytokeratin 7 (CK7)-positive/CK20-negative pattern (2 specimens). The 1
      sarcomatous/spindle cell type CC was chromogranin-negative and low molecular
      weight keratin (cell adhesion molecule 5.2)-positive, which excluded metastatic
      carcinoid. CONCLUSIONS: Classification of intrahepatic and extrahepatic CC in
      aspiration cytology specimens was achieved in a reliable manner concordant with
      the WHO histologic classification. Special types of CC with bland nuclear
      features posed a diagnostic challenge on cytologic evaluation, particularly the
      well differentiated CC with tubular architecture and the gastric foveolar type CC
      with mucin-producing tumor cells. The addition of core biopsy and/or ancillary
      studies, such as histochemical and immunochemical stains, were helpful in
      reaching the correct diagnosis.

PMID- 15952193
TI  - Single-cell microinjection of cytochrome c can result in gap junction-mediated
      apoptotic cell death of bystander cells in head and neck cancer.
AB  - BACKGROUND: Gap junction intercellular channels are required for metabolic
      cooperation between cells and regulate normal tissue homeostasis by means of the
      transfer of small molecules between contacting cells. Not surprisingly, the gap
      junction phenotype is frequently lost during carcinogenesis in human tissues
      (including those of the upper aerodigestive tract), freeing individual cancer
      cells from the growth control signals of normal surrounding tissues and less
      aggressive adjacent cancer cells. We hypothesized that gap junctional
      intercellular communication (GJIC) could mediate a bystander effect (apoptotic
      cell death) in squamous cell carcinoma of the head and neck (SCCHN) cells
      adjacent to individually targeted SCCHN cells. METHODS: Single-cell
      microinjection of cytochrome c was used to induce apoptosis in target SCCHN cells
      with endogenous GJIC activity and in an SCCHN cell line with exogenously
      introduced GJIC activity. Apoptosis was followed in target and surrounding
      bystander cells through light and time course microscopic characterization. All
      of the preceding experiments were carried out in the absence and presence of 18
      beta-glycerretinic acid, a pharmacologic inhibitor of GJIC. RESULTS: When
      cytochrome c was introduced into SCCHN cells with endogenous GJIC activity
      through single-cell microinjection, bystander effects (apoptosis of nontarget
      cells) were observed. When GJIC activity was blocked with the specific
      pharmacologic inhibitor of gap junctions, 18-beta-glycerretinic acid, a bystander
      effect was never seen in GJIC active SCCHN cell lines. CONCLUSIONS: Gap junction
      intercellular channels can mediate a bystander effect in SCCHN. Inconsistencies
      in our data will be discussed in the context of recent advances in this field, as
      well as our future research directions.

PMID- 15952194
TI  - Speech outcome after surgical treatment for oral and oropharyngeal cancer: a
      longitudinal assessment of patients reconstructed by a microvascular flap.
AB  - BACKGROUND: The aim of the study was to analyze speech outcome for patients with
      advanced oral/oropharyngeal cancer treated with reconstructive surgery and
      adjuvant radiotherapy. METHODS: Speech tests (communicative suitability,
      intelligibility, articulation, nasality, and consonant errors) were performed in
      a control group and in patients before treatment (n = 76), and 6 months (n = 51)
      and 12 months (n = 42) after treatment. RESULTS: Speech tests were significantly
      worse for patients before and after treatment compared with the controls. Speech
      did not improve between 6 and 12 months. After treatment, patients with T3-4
      tumors showed a significantly worse score for communicative suitability,
      intelligibility, and articulation than patients with T2 tumors. No significant
      differences were found for subsites after treatment, although patients with
      mobile tongue tumors showed the best results. CONCLUSION: Speech difficulties are
      significant, and with the knowledge of this study better counseling and vigilance
      as to speech difficulties may be possible in patients undergoing treatment for
      oral/oropharyngeal cancer.

PMID- 15952195
TI  - Molecular mediators of metastasis in head and neck squamous cell carcinoma.
AB  - BACKGROUND: The presence of regional metastasis in patients with head and neck
      squamous cell carcinoma (HNSCC) is a common and adverse event associated with
      poor prognosis and high mortality. Although significant improvements in standard
      therapies have increased the efficacy of local tumor management, the high
      incidence of tumor recurrence has resulted in limited improvements in overall
      survival rates. Understanding the molecular mechanisms that mediate HNSCC
      invasion and metastasis may enable identification of novel therapeutic targets
      for the prevention and management of tumor dissemination. METHODS: A literature
      review was performed. RESULTS: Several biologic mediators and mechanisms that
      have been implicated in HNSCC metastasis, such as cell adhesion molecules,
      proteolytic enzymes, growth factor signaling, metastasis suppressor genes, and
      chemokine receptors were reviewed. CONCLUSIONS: Prevention of HNSCC metastasis is
      an important clinical objective that requires an increased understanding of the
      molecular mechanisms of tumor invasion and dissemination.

PMID- 15952196
TI  - Melanoma metastatic to cervical lymph nodes: Can radiotherapy replace formal
      dissection after local excision of nodal disease?
AB  - BACKGROUND: Completion cervical lymphadenectomy is usually performed after
      excisional biopsy of nodal metastases from melanoma. Radiation (XRT) might be
      effective for some patients in lieu of formal lymph node dissection. METHODS:
      Thirty-six patients with parotid or cervical node metastases from melanoma were
      treated with excision of nodal disease and postoperative XRT without formal lymph
      node dissection. Radiation was delivered to the primary site (if known), the site
      of nodal excision, and the undissected ipsilateral neck. RESULTS: With a median
      follow-up of 5.3 years, the disease recurred within the regional basin in two
      patients and at distant sites in 14 patients. The actuarial 5-year regional
      control and distant metastasis-free survival rates were 93% and 59%,
      respectively. Two patients had a clinically significant side effect develop.
      CONCLUSIONS: The results of this study suggest that selected patients may receive
      regional XRT after local excision of nodal disease from melanoma in lieu of
      formal lymph node dissection.

PMID- 15952197
TI  - Extrathyroid carcinoma showing thymus-like differentiation (CASTLE) tumor--a new
      case report and review of literature.
AB  - BACKGROUND: We report a case of extrathyroid carcinoma showing thymus-like
      differentiation (CASTLE) tumor. METHODS: A 47-year-old man had a left neck mass
      that gradually enlarged over approximately 3 months. Sonography and CT scans
      showed a soft tissue mass located at the left parapharyngeal space with
      displacement of left carotid artery and submandibular gland. RESULTS: After total
      excision, the pathologic diagnosis was CASTLE tumor. The patient then received
      radiotherapy with a total dosage of 6600 cGy. After 21 months of postoperative
      follow up, there was no evidence of recurrence. CONCLUSION: Generally, the
      treatment of choice is surgical excision with or without radiotherapy. Because
      CASTLE tumors have been reported to be radiosensitive, however, and because local
      recurrence is common, surgical excision with postoperative radiotherapy is
      suggested.

PMID- 15952198
TI  - Hypoxia in head and neck cancer: how much, how important?
AB  - BACKGROUND: Hypoxia develops in tumors because of a less ordered, often chaotic,
      and leaky vascular supply compared with that in normal tissues. In preclinical
      models, hypoxia has been shown to be associated with treatment resistance and
      increased malignant potential. In the clinic, several reports show the presence
      and extent of tumor hypoxia as a negative prognostic indicator. This article
      reviews the biology and importance of hypoxia in head and neck cancer. METHODS: A
      review of literature was carried out and combined with our own experience on
      hypoxia measurements using exogenous and endogenous markers. RESULTS: Hypoxia can
      increase resistance to radiation and cytotoxic drugs and lead to malignant
      progression, affecting all treatment modalities, including surgery. Hypoxia
      measurements using electrodes, exogenous bioreductive markers, or endogenous
      markers show the presence of hypoxia in most head and neck cancers, and
      correlations with outcome, although limited, consistently indicate hypoxia as an
      important negative factor. Each hypoxia measurement method has disadvantages, and
      no "gold standard" yet exists. Distinctions among chronic, acute, and
      intermediate hypoxia need to be made, because their biology and relevance to
      treatment resistance differ. Reliable methods for measuring these different forms
      in the clinic are still lacking. Several methods to overcome hypoxia have been
      tested clinically, with radiosensitizers (nimorazole), hypoxic cytotoxins
      (tirapazamine), and carbogen showing some success. New treatments such as hypoxia
      mediated gene therapy await proper clinical testing. CONCLUSIONS: The hypoxia
      problem in head and neck cancer needs to be addressed if improvements in current
      treatments are to be made. Increased knowledge of the molecular biology of
      intermediate, severe, and intermittent hypoxia is needed to assess their
      relevance and indicate strategies for overcoming their negative influence.

PMID- 15952199
TI  - Insomnia improvement during antidepressant treatment and CLOCK gene polymorphism.
AB  - Sleep disturbances are commonly observed in mood disorders, and sleep
      manipulations can influence the clinical status. In the present study, we
      investigated the possible effect of the 3111 T/C circadian locomotor output
      cycles kaput (CLOCK) gene polymorphism on insomnia symptomatology during
      antidepressant treatment. One hundred seventy-eight inpatients were treated with
      fluvoxamine 300 mg/day (n = 147) or paroxetine 20-40 mg/day (n = 31), and either
      placebo or pindolol in a double blind design for 6 weeks. The severity of
      depressive symptoms was weekly assessed with the Hamilton Rating Scale for
      Depression (HAM-D). We observed a significantly higher presence of insomnia
      throughout the trial in homozygotes for the C variant (P = 0.026). Other
      demographic and clinical features were found not to be related with CLOCK
      polymorphisms. Overall, our findings may suggest that CLOCK genotype influences
      the time course of insomnia during antidepressant treatment. This, together with
      previous findings on this polymorphism could lead to a further dissection of the
      complexity of mood disorders.

PMID- 15952200
TI  - Hearing preservation after gamma knife stereotactic radiosurgery of vestibular
      schwannoma.
AB  - BACKGROUND: To evaluate the hearing preservation rate and to determine its
      prognostic factors after gamma knife (GK) stereotactic radiosurgery (SRS) in
      patients with vestibular schwannoma, the authors used a prospective study design
      to analyze these patients. METHODS: Between December 1997 and January 2002, 25
      patients with vestibular schwannoma with serviceable hearing were enrolled in the
      current study. The median tumor volume was 3.0 cc (0.16-9.1 cc). The prescription
      dose was 12.0 +/- 0.7 gray at an isodose line of 49.8 +/- 1.1%. The tumor control
      rate and complications were evaluated by focusing on hearing preservation and its
      prognostic factors. RESULTS: Based on radiologic study, the tumor control rate
      was 92% during the median follow-up period of 45 months. The trigeminal and
      facial nerve preservation rates were 95% and 100%, respectively. Thirteen (52%)
      of the 25 patients preserved serviceable hearing and 9 (36%) patients retained
      their pre-GK G-R grade levels after GK SRS. However, 16 patients showed hearing
      deterioration > 20 dB within 3-6 months and this trend continued for 24 months
      after the treatment. The maximum radiotherapy dose delivered to the cochlear
      nucleus was the single, significant prognostic factor of hearing deterioration.
      CONCLUSIONS: The authors concluded that a more sophisticated strategy to prevent
      hearing deterioration during the first 6 months post-GK SRS is necessary to
      improve long-term hearing preservation.

PMID- 15952201
TI  - Proliferation and progesterone receptor status in benign meningiomas are not age
      dependent.
AB  - BACKGROUND: Some authors have suggested that the biology of meningiomas differs
      according to a patient's age. Proliferation, vascularity, and hormonal status in
      meningiomas can be used to describe changes during aging. In the current study,
      proliferation activity with the Ki-67/MIB-1 antibody was evaluated by
      immunohistochemistry in meningioma tissue specimens from young and elderly
      patients. METHODS: Over the past 25 years, tissue samples from 1766 patients with
      meningiomas were evaluated. Of these, 588 tumor specimens from 554 patients who
      underwent surgery between 1990 and 2000 were evaluated immunohistochemically. The
      proliferation index (LI) and progesterone receptor (PR) in meningiomas were
      quantitatively estimated in elderly (age > or = 70 years) and young patients (age
      < 70 years). Patients' charts including surgical records, discharge letters,
      pathology reports, and imaging studies were reviewed. Correlations with
      histologic subtype, disease recurrence-free survival, resection grade, location,
      size, vascularity, and tumor calcification were calculated as well. Only patients
      with a well documented follow-up were included in the statistical evaluation (n =
      385). RESULTS: Compared with the young group of 344 patients with meningioma (age
      < 70 years; mean age, 51.9 years; range, 18-69 years), the elderly population
      (age > or = 70 years; n = 41; mean age, 74.9 years; range, 70-88 years) showed a
      male-to-female ratio of 3.2: 1. Both groups had an identical median Ki-67 LI of
      3.0% and a PR status of 56.1% versus 58.4 %. No statistically significant
      differences in disease recurrence-free survival could be found in the two groups.
      CONCLUSIONS: Proliferation rates and PR status in benign intracranial meningiomas
      did not appear to be age dependent.

PMID- 15952202
TI  - Infections in children and young adults with bone malignancies undergoing limb
      sparing surgery.
AB  - BACKGROUND: The epidemiology, risk factors, and efficacy of therapy for
      infections complicating limb-sparing surgery (LSS) are not understood completely.
      METHODS: The authors conducted a retrospective review of children and adolescents
      with bone malignancies who underwent LSS. RESULTS: One hundred three patients
      underwent 104 LSS procedures. Patients experienced a median of 4 infections
      (range, 0-13 infections), including focal bacterial infections in 67% of patients
      and bacteremia in 21% of patients. Infections at the LSS site occurred in 26% of
      patients, and 21% of patients developed orthopedic device infections (ODIs).
      Compared with patients without ODIs, patients who developed ODIs were more likely
      to be African American and to have wound infections, and they were less likely to
      have tumors of the femur than the tibia. In a multivariate analysis, only African
      American race and local infection at the LSS site retained a significant
      association with ODIs. Among survivors, patients who developed ODIs were more
      likely to undergo amputation (odds ratio [OR], 24.0; 95% confidence interval
      [95%CI], 5.1-114.0; P < 0.001) and were less likely to have good functional
      outcomes (OR, 0.02; 95%CI, 0.002-0.15; P < 0.001) compared with patients who did
      not have an ODI. Overall, only 1 of 22 patients with an ODI was treated
      successfully without removal of the orthopedic device or amputation. CONCLUSIONS:
      Current treatment for bone malignancies is complicated by an unexpectedly high
      incidence of infection. ODI was the most common reason for amputation and poor
      functional outcomes. The identification of risk factors for ODI may allow
      modifications of therapy that reduce the incidence and severity of infection, but
      prevention of all ODIs will require novel strategies.

PMID- 15952204
TI  - Real-time 3D echocardiography-guided transcatheter device closure of atrial
      septal defects.
AB  - We report our initial experience using real-time (live) three-dimensional (3D)
      transthoracic echocardiographic imaging under conscious sedation as a guide for
      transcatheter device closure of atrial septal defects. We believe this may be a
      feasible, safe, and effective alternative to the standard practice of
      transesophageal echocardiography, which requires general anesthesia and
      endotacheal intubation. Three-dimensional echocardiography may better define
      atrial septal anatomy and adjacent structures in planning for and performing
      percutaneous device closure of selected atrial septal defects.

PMID- 15952205
TI  - Structure and stability of beta-pleated sheets.
AB  - Beside alpha-helices, beta-sheets are the most common secondary structure
      elements of proteins. In this article, the question of structure and stability of
      parallel and antiparallel sheets of various lengths is addressed. All data
      obtained are compared to a selected set of protein structures. In antiparallel
      beta-sheets, one of the two possible H-bonded structures (containing 14 atoms in
      the H-bonded pseudoring) is energetically more favored and also more abundant in
      proteins than the other one (with 10 atoms involved in the pseudoring). Parallel
      beta-sheets and their subunits are energetically less stable and indeed found to
      occur more rarely in proteins. Antiparallel hairpins are disfavored compared to
      beta-sheets formed by sequentially separated strands. Agreement between theory
      and experimental data indicates that characterization of structural building
      blocks at an appropriately accurate level of theory is a useful tool to get
      insight into fundamentals of protein structure.

PMID- 15952206
TI  - Towards protein folding with evolutionary techniques.
AB  - We present design details and first tests of a new evolutionary algorithm
      approach to ab initio protein folding. It does not focus on dihedral angles
      exclusively, but mainly operates on introduction, extension, break-up, and
      destruction of secondary structure elements, given as correlated dihedral angle
      values. In first test applications to polyalanines (up to 60 residues) and random
      primary sequences (up to 40 residues), we demonstrate that this use of prior
      knowledge is well balanced: On the one hand, it ensures quick introduction of
      secondary structure elements if they are favorable for a given primary sequence,
      but still allows for efficient location of pure random coil solutions without
      enforcing any secondary structure elements, if folds of this type are preferred
      by the given primary sequence. Furthermore, the algorithm is clearly able to pack
      several secondary structure elements into favorable tertiary structure
      arrangements, although no part of the algorithm is explicitly designed to do
      this. In first test examples on real-life peptides between 21 and 44 residues
      from the Protein Data Bank, the quality of the results depends on the force field
      used (as expected); nevertheless, we can show that the algorithm is able to find
      structures in good agreement with the targets easily and consistently, if the
      force field allows for that.

PMID- 15952207
TI  - A theoretical study on the structures and energetics of hypothetical TiM(NCN)3
      compounds of the 3d transition metals.
AB  - Quasi-ternary cyanamides and carbodiimides of general formula AB(NCN)(3) with A
      not equal B have neither been predicted nor synthesized. Thus, hypothetical
      compounds of that kind containing 3d transition metals were considered (A = Ti, B
      = Mn, Fe, Co, Ni, Cu) by means of density-functional calculations on 34
      structural models, most of which were derived from chemically related phases.
      After performing structure optimizations based on the local-density
      approximation, the relative energetic orderings are rationalized in terms of
      geometrical factors such as molar volumes and polyhedral connections. Total
      energy generalized-gradient calculations evidence that the most stable models are
      enthalpically favored with respect to the elements. Even at ambient temperatures,
      the ternary phases are predicted as being thermodynamically stable in terms of
      their Gibbs free formation energies, especially if energetically competing and
      low-lying binaries (TiC, TiN) can be excluded by a kinetic reaction control. The
      best models are characterized by low-spin magnetic transition metals found in
      octahedral coordination, and the TiN(6) and MN(6) polyhedra either share faces or
      edges.

PMID- 15952208
TI  - Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue
      Vangl1 in neural tube defect patients.

PMID- 15952209
TI  - Clinical and molecular characterization of two adults with autosomal recessive
      Robinow syndrome.
AB  - Autosomal recessive Robinow syndrome is caused by mutations in ROR2 and is
      characterized by short stature, mesomelic limb shortening, brachydactyly,
      vertebral abnormalities, and a characteristic "fetal face" dysmorphology. We
      report the clinical and molecular studies on two adults with this condition.
      Besides typical skeletal and facial features, one patient developed
      hydronephrosis, nephrocalcinosis, and renal failure. The second patient had
      characteristic skeletal manifestations including severe spinal involvement and
      showed endocrinological abnormalities including elevated gonadotropic hormones.
      The facial phenotype in both patients remained distinctive into adulthood.
      Analysis of the ROR2 gene revealed a homozygous c.1937_1943delACAAGCT mutation in
      Patient 1, and compound heterozygosity for c.355C > T (p.R119X). and c.550C > T
      (p.R184C) in Patient 2.

PMID- 15952210
TI  - Total truncation of the molybdopterin/dimerization domains of SUOX protein in an
      Arab family with isolated sulfite oxidase deficiency.
AB  - We ascertained a patient with the full-blown phenotype of isolated sulfite
      oxidase deficiency in a consanguineous Arab family. The proband's phenotype
      included the presence of intractable seizures in the neonatal period, some
      dysmorphic features, neuroradiologic findings reminiscent of hypoxic ischemic
      encephalopathy and rapidly progressive brain destruction leading to severe
      neurodevelopmental impairment. Biochemically, the patient excreted a large amount
      of S-sulfocysteine with normal amounts of xanthene and hypoxanthine and had
      normal plasma uric acid, which was consistent with isolated sulfite oxidase
      deficiency. We report the identification of the first Arab mutation in SUOX, the
      gene for sulfite oxidase enzyme, in the ascertained family. The newly identified
      Arab mutation in the SUOX gene (a single nucleotide deletion, del G1244) is
      predicted to cause a frame shift at amino acid 117 of the translated protein with
      the generation of a stop codon and total truncation of the molybdo-pterin- and
      the dimerizing-domain(s) of SUOX protein expressed from the mutant allele. The
      identification of this new Arab SUOX mutation should facilitate pre-implantation
      genetic diagnosis and selection of unaffected embryos for future pregnancy in the
      ascertained family with the mutation and related families with the same mutation.

PMID- 15952211
TI  - DHCR7 mutations in Brazilian Smith-Lemli-Opitz syndrome patients.

PMID- 15952212
TI  - G59S mutation in the GJB2 (connexin 26) gene in a patient with Bart-Pumphrey
      syndrome.

PMID- 15952213
TI  - Clinical evaluation of an aerolysin-based screening test for paroxysmal nocturnal
      haemoglobinuria.
AB  - BACKGROUND: Recently, a toxin produced by Aeromonas hydrophila was demonstrated
      to bind directly to the glycosyl-phosphatidyl-inositol (GPI) anchor. After
      coupling it to a fluorescent dye and applying it in fluorescence-activated cell
      scanning (FACS), this property was exploited to detect GPI-negative cells in the
      diagnosis of paroxysmal nocturnal haemoglobinuria (PNH). METHODS: We used this
      reagent according to a very simple staining protocol followed by single-colour
      FACS and compared the results in patients with PNH and normal controls with those
      obtained with antibody-mediated detection of cells lacking GPI-anchored proteins.
      RESULTS: We observed very good concordance between the two methods, with
      correlation coefficients (R2) of quantified GPI-deficient cell populations
      ranging from 0.952 to 0.969. The lower limit of detection was determined at 0.50%
      GPI-negative cells, which was in the range obtained with double-colour staining
      with antibodies (0.20-1.00%, depending on the antibody). A significant
      correlation was observed between the fraction of GPI-negative granulocytes and
      laboratory parameters of haemolysis, with the erythrocyte creatine having the
      best correlation (R2 = 0.671, P < 0.0001). CONCLUSIONS: Using this protocol, we
      were able to reliably diagnose PNH with a high sensitivity. The test allows the
      identification of GPI-negative granulocyte populations as small as 0.5%.

PMID- 15952214
TI  - A new and a reclassified ICF patient without mutations in DNMT3B and its
      interacting proteins SUMO-1 and UBC9.
AB  - The ICF syndrome (immunodeficiency, centromeric instability, facial anomalies)
      (OMIM#242860) is a rare autosomal, recessively inherited disorder. Another rare
      condition, ischiadic hypoplasia, renal dysgenesis, immunodeficiency, and
      polydactyly (IHRDIP, OMIM#243340), displays features that resemble those of the
      ICF syndrome. Due to the overlapping symptoms in both syndromes, we asked whether
      a shared underlying molecular defect exists. Two patients, each with the clinical
      characteristics of one of these syndromes, were subjected to conventional
      cytogenetic analysis and the determination of the methylation state of satellite
      II DNA. We found that both displayed the two hallmark features of the ICF
      syndrome, namely hypomethylation and centromeric instability of chromosomes 1 and
      16. Therefore, we reclassified the patient previously diagnosed with the IHRDIP
      syndrome as an ICF patient. Since the majority of ICF patients are carriers of
      mutations in the methytransferase gene DNMT3B, we determined the sequence of its
      coding, splice site, and putative promoter region and analyzed its transcripts in
      both patients, without detecting any alterations. Similarly, the coding region of
      two DNMT3B-interacting proteins, SUMO-1 and UBC9, did not reveal mutations. With
      this study, the published number of patients that lack mutations in DNMT3B coding
      region increases to almost 40% of all ICF patients reported. It is, therefore,
      implied that a significant subset of ICF patients will have a yet unknown,
      alternative alteration, which may include the involvement of DNMT3B-interacting
      factors or aberrations of an independent pathway.

PMID- 15952215
TI  - Effect of cytological fixative and environmental conditions on nuclear
      morphometric characteristics of squamous epithelial cells in sputum.
AB  - BACKGROUND: Sputum samples for lung cancer screening trials are typically
      collected at home into specimen containers prefilled with cytologic fixative.
      Collection, transit, and storage expose samples to environmental conditions that
      may introduce artifacts that could confound evaluation. We examined whether the
      type of cytological fixative and exposure to different environmental conditions
      introduces artifacts that affect cytological analysis. METHODS: Sputum fixed in
      Saccomanno fluid (SAC), containing methyl, ethyl, and propyl alcohols and
      polyethylene glycol, or CytoRich Red solution (CRR), containing methyl and
      isopropyl alcohols and ethylene glycol, plus formaldehyde, was aliquoted and
      exposed for 8 h to the following conditions: (a) -20 degrees C freezer, (b) 60
      degrees C oven, (3) direct sunlight, and (4) room temperature. Cell morphometry
      was evaluated using computer-assisted image analysis (CAIA). RESULTS: The values
      obtained for CAIA analysis of sputum were affected by the type of fixative used.
      Temperature extremes and sunlight dramatically altered nuclear morphometry of SAC
      fixed cells. Artifacts were not observed in CRR-fixed cells. CONCLUSIONS: The
      effects of environmental exposures were minimized if sputum was placed in a
      formalin-containing fixative such as CRR. If an alcohol-based fixative such as
      SAC is used, sample handling, transport, and storage must be monitored to prevent
      the introduction of artifacts.

PMID- 15952216
TI  - Embryotropic effect of insulin-like growth factor (IGF)-I and its receptor on
      development of porcine preimplantation embryos produced by in vitro fertilization
      and somatic cell nuclear transfer.
AB  - Insulin-like growth factor (IGF)-I is a receptor-mediated autocrine/paracrine
      growth/survival factor for mammalian embryo development. The present study
      investigated the temporal expression and regulation of porcine IGF-I receptor
      (IGF-IR) mRNA and the role of IGF-I on development of porcine in vitro fertilized
      (IVF) and somatic cell nuclear transfer (SCNT) embryos. As assessed by semi
      quantitative reverse transcription-polymerase chain reaction (RT-PCR), the level
      of IGF-IR mRNA expression was high in unfertilized oocytes, 2-cell and 4-cell
      embryos and gradually decreased in 8-cell embryos, morulae, and blastocysts in
      both IVF and SCNT series. The IVF or SCNT embryos were cultured with 0, 1, 10,
      50, or 100 ng/ml IGF-I for 168 hr. Supplementing with 50 ng/ml IGF-I increased
      blastocyst formation and the number of cells in inner cell masses (ICMs) in both
      IVF and SCNT embryos. In a second experiment, more blastocysts were obtained when
      IVF or SCNT embryos were cultured for the first 48 hr or for the entire 168 hr
      with 50 ng/ml IGF-I compared to culturing without IGF-I for 48 hr or with IGF-I
      for the last 120 hr or without IGF-I for the entire 168 hr. Treating IVF or SCNT
      embryos with 50 ng/ml IGF-I significantly up-regulated IGF-IR mRNA compared to
      untreated control embryos. In conclusion, the present study demonstrated that IGF
      IR mRNA is expressed in porcine IVF and SCNT embryos, and that IGF-I improved the
      developmental competence of IVF and SCNT embryos through its specific receptors.

PMID- 15952217
TI  - Parthenogenetic and nuclear transfer rabbit embryo development and apoptosis
      after activation treatments.
AB  - Previous studies mainly evaluated the effect of culture conditions on
      preimplantation embryo apoptosis. In order to inhibit apoptosis of nuclear
      transfer (NT) embryos, putative apoptosis inhibitors were used to treat donor
      cells. However, little is known about the effect of activation treatments on
      embryo apoptosis. We firstly investigated the effect of various parthenogenetic
      activation (PA) treatments on embryo development, blastocyst cell number, and
      apoptosis, and then one of these activation treatments proved to be most
      efficient was selected for activation rabbit NT embryos. The activation by
      electrical pulses and 30 min later, electroporation with 25 muM D-myoinositol
      1,4,5-trisphosphate (IP3) in Ca(2+)- and Mg(2+)-free PBS, then exposure to 2.0 mM
      6-dimethylaminopurine (6-DMAP) for 3 hr effectively activated rabbit oocytes, and
      resulted in significantly a higher blastocyst development rate (72.7%) and total
      cell number (175 +/- 14.1), and markedly lower apoptosis level of blastocyst (4.3
      +/- 0.5) than all the other groups. When the same activation protocol was applied
      in NT embryo activation, we found that exposure of the embryos to 6-DMAP for 3 hr
      could decrease the apoptosis level of blastocyst and increase blastocyst rate and
      cell number. The results demonstrate that oocyte activation affects not only
      embryo development and quality but also embryo apoptosis.

PMID- 15952218
TI  - Novel approach to percutaneous stent implantation for coarctation of the aorta:
      the railway technique.
AB  - Percutaneous stent implantation is a widely accepted therapeutic procedure for
      recurrent coarctation of the aorta. Distal stent migration during deployment is
      not uncommon and can result in vascular dissection. The following report
      describes the creation of an arterial railway in two patients with coarctation.
      The railway allowed for stent placement with minimal movement of the
      balloon/stent assembly during deployment. This strategy may decrease the risk of
      stent malposition and could be particularly useful in cases where anatomy is
      difficult.

PMID- 15952219
TI  - Kinetic determinations of molecular interactions using Biacore--minimum data
      requirements for efficient experimental design.
AB  - Reliable kinetic estimates can be obtained from significantly less data than is
      commonly used today, particularly in the characterization of 1:1 interactions
      involving low molecular weight compounds and proteins. We have designed a
      rational and cost-effective strategy to determine kinetic constants using
      Biacore's surface plasmon resonance-based biosensors and show that the number of
      measurements necessary for accurate kinetic determinations can be greatly
      reduced, increasing sample throughput and saving sample material. Simulated and
      measured data for a range of possible 1:1 interactants were studied to find the
      minimum requirements of a data set for kinetic analysis. The results showed that
      kinetic constants in the region 10(4) < k(a) < 10(7) M(-1) s(-1) (association)
      and 10(-4) < k(d) < 10(-1) s(-1) (dissociation) could easily be determined in a
      1:1 interaction model. Owing to the information-dense nature of Biacore data,
      only two sample concentrations were necessary to reliably determine the kinetics.
      A standard sample concentration series consisting of 10-fold dilutions between
      approximately 10 microM and approximately 1 nM consistently provided at least two
      concentrations with sufficient information about the interaction in this region.
      Determinations of the constants became increasingly unreliable outside this
      region. If the rate constants prove to be outside the specified region or the
      data fits poorly to the 1:1-MTL model, more experiments are required. General
      recommendations for the design of a cost-effective assay to deliver reliable
      kinetic measurements are provided.

PMID- 15952221
TI  - Investigation of ethylene dimerization over faujasite zeolite by the ONIOM
      method.
AB  - Ethylene dimerization was investigated by using an 84T cluster of faujasite
      zeolite modeled by the ONIOM3(MP2/6-311++G(d,p):HF/6-31G(d):UFF) method.
      Concerted and stepwise mechanisms were evaluated. In the stepwise mechanism, the
      reaction proceeds by protonation of ethylene to form the surface ethoxide and
      then C--C bond formation between the ethoxide and the second ethylene molecule to
      give the butoxide product. The first step is rate-determining and has an
      activation barrier of 30.06 kcal mol(-1). The ethoxide intermediate is rather
      reactive and readily reacts with another ethylene molecule with a smaller
      activation energy of 28.87 kcal mol(-1). In the concerted mechanism, the reaction
      occurs in one step of simultaneous protonation and C--C bond formation. The
      activation barrier is calculated to be 38.08 kcal mol(-1). Therefore, the
      stepwise mechanism should dominate in ethylene dimerization.

PMID- 15952222
TI  - The influence of promoters and poisons on carbon monoxide adsorption on Rh(100):
      a DFT study.
AB  - Density functional theory calculations were performed to determine the pairwise
      lateral interaction energies between carbon monoxide and coadsorbed elements from
      the first three rows of the periodic table on a Rh(100) surface. The atoms were
      placed in a c(2x2) arrangement of fourfold hollow sites and the carbon monoxide
      probe molecule in a p(2x2) arrangement, so that each CO molecule had four atoms
      as nearest neighbours. The alkali atoms show an attractive interaction with CO
      while the other atoms show a repulsive interaction. For second-row elements the
      maximum repulsion is at nitrogen and for third-row elements at sulphur. Attempts
      to correlate the interaction energies with properties of the system, such as
      electronegativity, distances, or change in work function, failed, which implies
      that each combination of adsorbates needs to be calculated separately.

PMID- 15952223
TI  - Starting from scratch: the rise and fate of carbon atoms.

PMID- 15952224
TI  - Size tuning, functionalization, and reactivation of Au in TiO2 nanoreactors.

PMID- 15952225
TI  - Simultaneous conversion of methane and methanol into gasoline over bifunctional
      Ga-, Zn-, In-, and/or Mo-modified ZSM-5 zeolites.

PMID- 15952226
TI  - Quantification of cation-pi interactions in protein-ligand complexes: crystal
      structure analysis of Factor Xa bound to a quaternary ammonium ion ligand.

PMID- 15952229
TI  - An in-gel digestion procedure that facilitates the identification of highly
      hydrophobic proteins by electrospray ionization-mass spectrometry analysis.
AB  - A procedure is described for in-gel tryptic digestion of proteins that allows the
      direct analysis of eluted peptides in electrospray ionization (ESI) mass
      spectrometers without the need of a postdigestion desalting step. It is based on
      the following principles: (a) a thorough desalting of the protein in-gel before
      digestion that takes advantage of the excellent properties of acrylamide polymers
      for size exclusion separations, (b) exploiting the activity of trypsin in water,
      in the absence of inorganic buffers, and (c) a procedure for peptide extraction
      using solvents of proven efficacy with highly hydrophobic peptides. Quality of
      spectra and sequence coverage are equivalent to those obtained after digestion in
      ammonium bicarbonate for hydrophilic proteins detected with Coomassie blue, mass
      spectrometry-compatible silver or imidazole-zinc but are significantly superior
      for highly hydrophobic proteins, such as membrane proteins with several
      transmembrane domains. ATPase subunit 9 (GRAVY 1.446) is a membrane protein
      channel, lipid-binding protein for which both the conventional in-gel digestion
      protocol and in solution digestion failed. It was identified with very high
      sequence coverage. Sample handling after digestion is notably simplified as
      peptides are directly loaded into the ESI source without postdigestion
      processing, increasing the chances for the identification of hydrophobic
      peptides.

PMID- 15952230
TI  - Mass profiling-directed isolation and identification of a stage-specific
      serologic protein biomarker of advanced prostate cancer.
AB  - Carcinoma of the prostate (CaP) is the second leading cause of cancer-related
      mortality among American men. While high cure rates are associated with localized
      CaP, no cure exists for advanced recurrent disease. At present there are no known
      serologic biomarkers specific to this stage of the disease. Several groups have
      used mass spectrometry (MS) based mass profiling (MP) combined with multivariate
      analysis to identify diagnostically predictive protein peaks for CaP in serum and
      tissues. Nevertheless, an appreciable level of skepticism exists for MP
      attributed primarily to a lack of definitive protein characterization. To address
      this problem, we have applied an approach that combines MP with a whole-protein
      based top-down separation strategy for the identification of a stage-specific
      marker in a group comprising 16 patients with CaP (metastatic and localized
      disease) and 15 healthy individuals. MP, combined with multivariate analysis,
      yielded 17 serum proteins specific to metastatic disease. A single protein
      detected at m/z 7771 was found to be significantly decreased in the sera of all
      the metastatic CaP patients but not in localized CaP or healthy individuals. This
      protein was therefore chosen as the primary candidate for further analysis. The
      complex nature of the serologic proteome necessitated an isolation strategy that
      included a C18 prefractionation, followed by multidimensional liquid
      chromatography and, finally, two-dimensional gel electrophoresis. The separation
      process was monitored by UV-Vis and matrix-assisted laser desorption/ionization
      time of flight MS analysis. This strategy was found to greatly facilitate
      subsequent MS characterization of the unknown protein, which was identified as
      platelet factor 4, a chemokine with prothrombolytic and antiangiogenic
      activities. Confirmation was achieved using both Western blot analysis and enzyme
      linked immunosorbent assay. With the growing interest in using MP for patient
      classification and diagnosis, our approach and its variations should be powerful
      in the separation and characterization of proteins following MP.

PMID- 15952231
TI  - Characterization of wheat gliadin proteins by combined two-dimensional gel
      electrophoresis and tandem mass spectrometry.
AB  - A proteomics-based approach was used for characterizing wheat gliadins from an
      Italian common wheat (Triticum aestivum) cultivar. A two-dimensional gel
      electrophoresis (2-DE) map of roughly 40 spots was obtained by submitting the 70%
      alcohol-soluble crude protein extract to isoelectric focusing on immobilized pH
      gradient strips across two pH gradient ranges, i.e., 3-10 or pH 6-11, and to
      sodium dodecyl sulfate-polyacrylamide electrophoresis in the second dimension.
      The chymotryptic digest of each spot was characterized by matrix-assisted laser
      desorption/ionization-time of flight mass spectrometry and nano electrospray
      ionization-tandem mass spectrometry (MS/MS) analysis, providing a "peptide map"
      for each digest. The measured masses were subsequently sought in databases for
      sequences. For accurate identification of the parent protein, it was necessary to
      determine de novo sequences by MS/MS experiments on the peptides. By partial mass
      fingerprinting, we identified protein molecules such as alpha/beta-, gamma-,
      omega-gliadin, and high molecular weight-glutenin. The single spots along the 2
      DE map were discriminated on the basis of their amino acid sequence traits. alpha
      Gliadin, the most represented wheat protein in databases, was highly conserved as
      the relative N-terminal sequence of the components from the 2-DE map contained
      only a few silent amino acid substitutions. The other closely related gliadins
      were identified by sequencing internal peptide chains. The results gave insight
      into the complex nature of gliadin heterogeneity. This approach has provided us
      with sound reference data for differentiating gliadins amongst wheat varieties.

PMID- 15952232
TI  - Genistein blocks homocysteine-induced alterations in the proteome of human
      endothelial cells.
AB  - Dietary isoflavones from soy are suggested to protect endothelial cells from
      damaging effects of endothelial stressors and thereby to prevent atherosclerosis.
      In search of the molecular targets of isoflavone action, we analyzed the effects
      of the major soy isoflavone, genistein, on changes in protein expression levels
      induced by the endothelial stressor homocysteine (Hcy) in EA.hy 926 endothelial
      cells. Proteins from cells exposed for 24 h to 25 microM Hcy alone or in
      combination with 2.5 microM genistein were separated by two-dimensional gel
      electrophoresis and those with altered spot intensities were identified by
      peptide mass fingerprinting. Genistein reversed Hcy-induced changes of proteins
      involved in metabolism, detoxification, and gene regulation; and some of those
      effects can be linked functionally to the antiatherosclerotic properties of the
      soy isoflavone. Alterations of steady-state levels of cytoskeletal proteins by
      genistein suggested an effect on apoptosis. As a matter of fact genistein caused
      inhibition of Hcy-mediated apoptotic cell death as indicated by inhibition of DNA
      fragmentation and chromatin condensation. In conclusion, proteome analysis allows
      the rapid identification of cellular target proteins of genistein action in
      endothelial cells exposed to the endothelial stressor Hcy and therefore enables
      the identification of molecular pathways of its antiatherosclerotic action.

PMID- 15952233
TI  - A comparative evaluation of software for the analysis of liquid chromatography
      tandem mass spectrometry data from isotope coded affinity tag experiments.
AB  - The options available for processing quantitative data from isotope coded
      affinity tag (ICAT) experiments have mostly been confined to software specific to
      the instrument of acquisition. However, recent developments with data format
      conversion have subsequently increased such processing opportunities. In the
      present study, data sets from ICAT experiments, analysed with liquid
      chromatography/tandem mass spectrometry (MS/MS), using an Applied Biosystems
      QSTAR Pulsar quadrupole-TOF mass spectrometer, were processed in triplicate using
      separate mass spectrometry software packages. The programs Pro ICAT, Spectrum
      Mill and SEQUEST with XPRESS were employed. Attention was paid towards the extent
      of common identification and agreement of quantitative results, with additional
      interest in the flexibility and productivity of these programs. The comparisons
      were made with data from the analysis of a specifically prepared test mixture,
      nine proteins at a range of relative concentration ratios from 0.1 to 10 (light
      to heavy labelled forms), as a known control, and data selected from an ICAT
      study involving the measurement of cytokine induced protein expression in human
      lymphoblasts, as an applied example. Dissimilarities were detected in peptide
      identification that reflected how the associated scoring parameters favoured
      information from the MS/MS data sets. Accordingly, there were differences in the
      numbers of peptides and protein identifications, although from these it was
      apparent that both confirmatory and complementary information was present. In the
      quantitative results from the three programs, no statistically significant
      differences were observed.

PMID- 15952234
TI  - Report on the first congress of the Spanish Proteomics Society.
AB  - This report describes the first congress of the Spanish Proteomics Society
      (SEProt) and the Foundation Meeting of the European Proteomics Association
      (EuPA), which were held in Cordoba, Spain, February 13-17, 2005. The EuPA meeting
      joined together thirty European representatives from 17 national European
      proteomics organisations to discuss the opportunity of creating a supranational
      association aimed to promote all aspects of proteomics as a scientific discipline
      throughout Europe. The main subjects of the SEProt congress, which was attended
      by over 350 researchers mainly from Spain and other European countries, were the
      current status and applications of proteomics in medical and biological sciences.

PMID- 15952235
TI  - HUPO Brain Proteome Project Pilot Studies: bioinformatics at work.
AB  - The data acquisition phase of initial pilot studies (human and mouse brain
      samples) of the Human Proteome Organisation (HUPO) Brain Proteome Project (BPP)
      is now complete and the data generated by the participating laboratories has been
      submitted to the central Data Collection Center. The BPP Bioinformatics Group met
      on 8th April 2005 at the European Bioinformatics Institute (Hinxton, UK) to
      discuss strategies for the reanalysis of the pooled data from all the
      participating laboratories. A summary of the results of the data reprocessing
      will be presented at the 4th HUPO World Congress that will be held in
      August/September 2005.

PMID- 15952236
TI  - Delay of coupling caused by excess additives.
AB  - Use of excess quantity of additives such as 1-hydroxybenzotriazole, 1-hydroxy-7
      azabenzotriazole, or 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine could retard
      carbodiimide-mediated peptide coupling or aminolysis of the active esters in
      organic solvents generally employed in peptide chemistry. Solubility test and
      infrared spectroscopic data suggested that the amine components interacted with
      the additives to form some aggregates, which were less reactive toward acylation.
      The use of 0.1 equimolar additives against carboxyl components or carbodiimides
      was advantageous for rapid and efficient coupling reaction, especially when the
      carboxyl components were amino acids carrying urethane type N-protecting groups.

PMID- 15952237
TI  - A theoretical study of pentacyclo-undecane cage peptides of the type [Ac-X-Y
      NHMe].
AB  - The conformational preferences of peptides of the type, Ac-X-Y-NHMe, where X and
      Y = Ala, cage and Pro, were studied by means of computational techniques within
      the framework of a molecular mechanics approach. For each of the eight peptide
      analogues, extensive conformational searches were carried out using molecular
      dynamics (MD) and simulated annealing (SA) protocols in an iterative fashion.
      Both results are in good agreement and complement each other. The conformational
      search indicates that the cage residue restricts the conformational freedom of
      the dipeptide considerably in comparison with the other model residues used. This
      study revealed that proline exhibits a greater tendency in promoting reverse-turn
      characteristics in comparison to the cage peptides, which show promising beta
      turn characteristics. It was also found that 300-500 K is not sufficient to
      overcome rotational barriers for cage peptides. In all cases, the low-energy
      conformers have a tendency to form bent structures.

PMID- 15952238
TI  - A psbA mutation in Kochia scoparia (L) Schrad from railroad rights-of-way with
      resistance to diuron, tebuthiuron and metribuzin.
AB  - Kochia [Kochia scoparia (L) Schrad] has become resistant to many herbicides used
      in cropland and railroad rights-of-way in North Dakota and Minnesota. Kochia
      scoparia plants that had survived annual treatments with diuron and tebuthiuron
      were sampled along railroad rights-of-way in North Dakota and Minnesota. The
      samples were screened in the greenhouse for resistance to diuron, tebuthiuron,
      metribuzin and bromoxynil from 0.5x to 32x the recommended use rates. A resistant
      K scoparia accession (MN-3R) was confirmed with resistance up to 16-fold higher
      than recommended use rates for tebuthiuron and diuron and up to 4-fold higher for
      metribuzin. However, the resistant K scoparia accession was susceptible to
      bromoxynil even at 50% of the recommended use rate. The herbicide binding region
      of the psbA gene fragment of eight resistant (R) and seven susceptible (S) K
      scoparia accessions was PCR-amplified and sequenced for detection of mutations.
      The psbA gene of four R K scoparia accessions was mutated at residue 219 with
      substitution of isoleucine for valine (GenBank accession number AY251265). The
      seven S K scoparia accession sequences were wild-type at this residue (GenBank
      accession number AY251266). The other four R accessions sequences showed a
      previously known triazine R mutation with substitution of glycine for serine at
      residue 264. All 15 K scoparia accessions were wild-type at all other psbA
      residues within the region analyzed. Resistance to diuron, tebuthiuron and
      metribuzin among the railroad rights-of-way K scoparia is probably due to the
      mutation at residue 219 of the psbA gene in some plants, but due to the
      previously reported Ser(264)Gly substitution in other plants. Target-site
      resistance associated with a change of valine to isoleucine at residue 219 of the
      psbA target-site in weeds has previously been reported for Poa annua L selected
      in diuron-treated grass seed fields, and for Amaranthus powelli S Wats selected
      in linuron-treated carrot fields. This is the first report of the mutation in
      herbicide-resistant K scoparia.

PMID- 15952239
TI  - Reciprocal mutations in TM2/TM3 in a D2 dopamine receptor background confirms the
      importance of this microdomain as a selective determinant of para-halogenated 1,4
      disubstituted aromatic piperazines.
AB  - We recently demonstrated that in the D4 dopamine receptor the aromatic
      microdomain that spans the interface of the second and third transmembrane (TM)
      domains influences the high affinity interactions of extremely D4-selective
      ligands possessing a 1,4-disubstituted aromatic piperazine/piperidine (1,4-DAP)
      structure. On the basis of their substructural features and patterns of
      sensitivity to mutations constructed in a D4 receptor background, the D4
      selective 1,4-DAPs were categorized as having two distinct modes of binding that
      we named mode-1 and mode-3 [1]. Here we extend these findings of the ligand
      receptor structure-affinity relationships for some of these highly D4-selective
      1,4-DAPs by measuring the effect of the corresponding reciprocal TM2/TM3
      mutations constructed in a D2 dopamine receptor background on the binding
      affinity of the para-halogenated mode-1 ligands L750,667 and FAUC213. The results
      indicate that the D2-V2.61F + FV3.28-3.29LM mutant binds L750,667 and FAUC213
      with significantly increased affinity, i.e., its binding profile becomes more D4
      like. These findings further support the assignment of the TM2/TM3 aromatic
      microdomain encompassing positions 2.61 and 3.28-3.29 as a 1,4-DAP D4-selectivity
      microdomain and highlights the importance of the precise emplacement of aromatics
      in this microdomain as key to the selective molecular recognition of L750,667 and
      FAUC213.

PMID- 15952240
TI  - Rhodopsin: a structural primer for G-protein coupled receptors.
AB  - An overview of the rhodopsin crystal structure provides a structural basis for
      understanding the structures and functions of other G-protein coupled receptors
      (GPCRs). All of the structural details observed to date for rhodopsin will not
      necessarily carry over to other GPCRs, but major features such as the arrangement
      of the seven transmembrane helices, the retinal/ligand binding site, the D(E)RY
      and NPXXY sequence and structural motifs, and the bent helices are likely
      characteristics of the GPCRs most closely related to rhodopsin. A general view of
      these structural features is presented here.

PMID- 15952241
TI  - Recent advances in melatonin receptor ligands.
AB  - Melatonin is a hormone exerting its multiple actions mainly through two G-protein
      coupled receptors MT(1) and MT(2). Exploring the physiological role of each of
      these subtypes requires subtype selective MT(1) and MT(2) ligands. While several
      MT(2)-selective ligands were developed in the 1990s, no selective agonists and
      antagonists for the MT(1) subtype were described. The present article reviews
      mela toninergic ligands developed in the current millennium focusing on subtype
      selective agents and on drug candidates. Notable compounds are the MT(1)
      selective agonists 35 and 134, MT(1)-selective antagonists 117 and 131, MT(2)
      selective agonists 58, 70, 79, 97 and 125, MT(2)-selective antagonists 27, 73 and
      119, and the highly potent non-selective agonist 120. The non-selective agonists
      agomelatine 2, and ramelteon 87 are drug candidates as antidepressive agent and
      for the treatment of insomnia and circadian rhythm disfunction, respectively.

PMID- 15952242
TI  - Chirospecific and subtype selective dopamine receptor binding of heterocyclic
      methoxynaphthamide analogs.
AB  - Employing the D(3) and D(4) selective methoxynaphthalines nafadotride and FAUC
      182, respectively, as lead compounds, the pyrazolo[1,5-a]pyridine-3-carboxamides
      of type 1a and 2a as well as their 2-substituted regioisomers 1b and 2b were
      synthesized when following an ex-chiral pool approach. Dopamine receptor binding
      studies involving the target compounds (1a,b, 2a,b) and the respective optical
      antipodes ent-1a,b and ent-2a,b revealed the heterocyclic carboxamide 2a as a
      strong and selective D(4) ligand (K(i) = 8.6 nM). According to a mitogenesis
      assay, 2a shows D(4) partial agonist effects (29%, EC(50) = 6.7 nM) and, thus,
      might be of interest for the treatment of sexual dysfunction.

PMID- 15952243
TI  - Delineation of receptor-ligand interactions at the human histamine H1 receptor by
      a combined approach of site-directed mutagenesis and computational techniques -
      or - how to bind the H1 receptor.
AB  - Histamine H(1) antagonists or "antihistamines" are one of the most prescribed
      drug families in Western countries. They exert their effect by binding to the
      histamine H(1) receptor, a receptor belonging to the class of rhodopsin-like G
      protein-coupled receptors (GPCRs). In this review, the binding of ligands to the
      human histamine H(1) receptor with respect to site-directed mutagenesis studies
      and molecular modeling techniques is described. The ligands described include
      agonists (histamine and histaprodifens), a stereoselective partial agonist
      (lisuride), and selected inverse agonists (mepyramine, acrivastine and
      triprolidine).

PMID- 15952244
TI  - New amides of 5-acylamino-3-methyl-4-isothiazolecarboxylic acid and their
      immunotropic activity.
AB  - Several new amides 4 of 5-substituted 3-methyl-4-isothiazolecarboxylic acid were
      obtained. These compounds have acetylamino or benzoylamino groups in position 5
      of the isothiazole ring. In position 4, the carboxylic group was transformed in
      the amides using amino-acid esters. Activities of the obtained derivatives were
      checked in the humoral immune response and delayed type hypersensitivity reaction
      to sheep red blood cells (SRBCs) in vivo.

PMID- 15952245
TI  - Convergent solid-phase synthesis of hirudin.
AB  - Hirudin variant 1 (HV1), a small protein consisting of 65 amino acids and three
      disulfide bonds, was synthesized by using Fmoc-based convergent methods on 2
      chlorotrityl resin (CLTR). The linear sequence was assembled by the sequential
      condensation of 7 protected fragments, on the resin-bound 55-65 fragment. The
      conditions of fragment assembly were carefully studied to determine the most
      efficient synthetic protocol. Crude reduced [Cys(16, 28)(Acm)]-HV1 thus obtained
      was easily purified to homogeneity by RP-HPLC. Disulfide bridges were
      successfully formed by a two-step procedure, involving an oxidative folding step
      to form Cys(6)-Cys(14) and Cys(22)-Cys(39) linkages, followed by iodine oxidation
      to form the Cys(16)-Cys(28) bond. The correct disulfide bond alignment was
      established by peptide mapping using Staphylococcus aureus V8 protease at pH 4.5.

PMID- 15952246
TI  - Casein-hydrolyzing activity of sIgA antibodies from human milk.
AB  - During pregnancy and immediately after delivery (i.e. at the beginning of
      lactation), the female organism is frequently characterized by an immune status
      similar to that of patients with autoimmune diseases. In addition, lactation is
      associated with an appearance of catalytically active antibodies or abzymes
      (Abzs) with DNAse, RNase, ATPase, amylolitic, protein kinase and lipid kinase
      activities in breast milk. However, until now there were no examples of human
      milk Abzs with a proteolytic activity. We present the first evidence that
      electrophoretically and immunologically homogeneous human milk sIgAs possess a
      beta-casein-hydrolyzing activity different from known proteases. Abzs
      specifically hydrolyze both human and bovine beta-caseins but not many other
      proteins tested. Using different methods including in situ analysis of
      proteolytic activity in a gel after SDS-PAGE it was shown that the observed
      proteolytic activity is an intrinsic property of human milk polyclonal sIgAs.
      Specific inhibitors of acidic and thiol proteases demonstrated a weak effect on
      proteolytic activity of Abzs, while a specific inhibitor of serine proteases
      (AEBSF) significantly inhibited the proteolytic activity of the abzymes. The K(M)
      value for human casein as a substrate was estimated (7.3 microM). Our findings
      suggest that the immune system of clinically healthy mothers can generate IgAs
      with a beta-casein-specific serine protease-like activity.

PMID- 15952247
TI  - Evaluation of phenylaminopyrimidines as antifungal protein kinase inhibitors.
AB  - The effects of diverse phenylaminopyrimidines (PAP), namely PAP-pyridines (type
      A), PAP-pyrazoles (type B) and PAP-thiazoles (type C), on Neurospora crassa Shear
      & Dodge has been investigated. The results revealed that type A strongly inhibit
      the in vitro growth of N crassa, whereas types B and C are much less active. A
      significant correlation was observed between the Neurospora growth inhibition and
      the intrinsic activity of type A compounds on the cyclin-dependent protein kinase
      p34(CDC2) of starfish, suggesting that the target of phenylaminopyrimidines in
      fungi is a cyclin-dependent protein kinase (CDK). The phenylaminopyrimidine
      binding CDKs Phoss (major band) and CDC2 (minor band) involved in phosphorus
      uptake, glycogen synthesis and the cell cycle were identified from N crassa by
      affinity chromatography on phenylaminopyrimidine-sepharose. Comparative
      experiments with different protein kinases revealed the importance of the side
      chain of phenylaminopyrimidines for their target selectivity. A type B compound
      was found to selectively inhibit the MAP-kinase OS-2 involved in the
      osmoregulatory pathway of Neurospora.

PMID- 15952248
TI  - Advances in prostate cancer research. Part II.

PMID- 15952249
TI  - Advances in prostate cancer research. Part III.

PMID- 15952250
TI  - Under-investigated area in prostate cancer: cross talk between the bone
      microenvironment and prostate cancer bone metastasis.

PMID- 15952251
TI  - Prevalence and factors involved in discordant responses to highly active
      antiretroviral treatment in a closely followed cohort of treatment-naive HIV
      infected patients.
AB  - The prevalence and the factors involved in discordant responses to highly active
      antiretroviral therapy were analysed in a closely followed cohort of 51 naive HIV
      infected patients at 48 weeks. A complete treatment response was considered as an
      increase in CD4 cell count of >or=50 cells/mm3 with a >or=1 log10 decrease in
      viral load or viral suppression. Virologic response (<50 CD4+ cells/mm3 increase)
      and immune response (<1 log10 decrease in viral load) were observed in 15.7% and
      5.8% of the patients, respectively. We demonstrated that the prevalence of
      virologic response decreased at week 72 and disappeared after 96 weeks of
      treatment. This slower response did not correlate with protease inhibitor-based
      (PI-based) regimens or HCV coinfection. On the other hand, immune response in our
      cohort could be easily attributable to a simple mechanism, i.e. irregular
      treatment compliance.

PMID- 15952252
TI  - Maker of heart device kept flaw from doctors.

PMID- 15952253
TI  - House approves a stem cell bill opposed by Bush; margin is not veto-proof;
      bipartisan Senate support may set up showdown over federal funds.

PMID- 15952254
TI  - Despite vow, drug makers still withhold data.

PMID- 15952255
TI  - From stem cell opponents, an embryo crusade.

PMID- 15952256
TI  - Avian flu special: deadly combinations.

PMID- 15952257
TI  - Avian flu special: masking our ignorance.

PMID- 15952258
TI  - Articular cartilage and osteoarthritis.
AB  - Articular cartilage, which makes possible the painless, low-friction movement of
      synovial joints, consists of a sparsely distributed population of highly
      specialized cells called chondrocytes that are embedded within a matrix and
      provide articular cartilage with remarkable mechanical properties. Chondrocytes
      form the tissue matrix macromolecular framework from three classes of molecules:
      collagens, proteoglycans, and noncollagenous proteins. The matrix protects the
      cells from injury resulting from normal joint use, determines the types and
      concentrations of molecules that reach the cells, acts as a mechanical signal
      transducer for the cells, and helps maintain the chondrocyte phenotype.
      Throughout life, articular cartilage undergoes internal remodeling as the cells
      replace matrix macromolecules lost through degradation. Aging decreases the
      ability of chondrocytes to maintain and restore articular cartilage and thereby
      increases the risk of degeneration of the articular cartilage surface.
      Progressive degeneration of articular cartilage leads to joint pain and
      dysfunction that is clinically identified as osteoarthritis. Investigation
      regarding the pathogenesis of posttraumatic osteoarthritis, the form of
      osteoarthritis that develops following joint injury, is helping to explain the
      development and progression of joint degeneration.

PMID- 15952259
TI  - All-terrain vehicle-related central nervous system injuries in Oklahoma.
AB  - OBJECTIVE: Determine the statewide, population-based incidence and epidemiology
      of all-terrain vehicle (ATV)-related severe central nervous system (CNS) injuries
      in Oklahoma. METHODS: Hospitalized and fatal traumatic brain injuries and spinal
      cord injuries are reportable conditions in Oklahoma. Professionally trained staff
      reviewed all medical examiner and hospital medical records. RESULTS: From 1992
      through 2002 there were 391 persons hospitalized (n=353) or died (n=38) from an
      ATV-related neurologic injury (average annual rate 1.1/100,000 population),
      including 369 traumatic brain injuries and 18 spinal cord injuries and 4 persons
      with both injuries. These accounted for 1% of total CNS injuries in Oklahoma.
      Forty-five percent of persons who died were under 16 years of age. An average of
      23 ATV-related injuries per year occurred before 1998; the number of cases
      doubled in 1999 and 2000 (mean=46) and tripled in 2002 and 2003 (mean=69). Rates
      were highest among males 15-24 (4.1/100,000) and 5-14 (3.8/100,000) and among
      whites (1.2/100,000). Persons who collided with a stationary or moving object
      were significantly more likely to suffer a fatal traumatic brain injury than
      those in non-collision events (OR 3.0, 95% CI 1.4, 6.8). Rollover of the ATV
      occurred in 38% of ATV incidents, and in 28% of traumatic brain injury
      fatalities, it occurred without a preceding collision. CONCLUSIONS: ATV use can
      result in significant neurologic morbidity and mortality, especially among
      children and young adults. Heightened public awareness and parental education on
      the dangers of these vehicles is imperative. State legislation restricting the
      use of ATVs among children under the age of 16 years is recommended. Vehicle
      design changes such as lowering the center of gravity and installing rollover
      protective structures should be considered.

PMID- 15952260
TI  - Fill-in and infill errors in order memory.
AB  - Many current models of memory are specified with enough detail to make
      predictions about patterns of errors in memory tasks. However, there are often
      not enough empirical data available to test these predictions. We report two
      experiments that examine the relative frequency of fill-in and infill errors. In
      immediate serial recall tasks, subjects sometimes incorrectly recall item N too
      soon, placing it in position N-1. The error of interest is which item is recalled
      after this initial mistake. A fill-in error is the tendency to recall item N-1
      next, whereas an infill error is the tendency to recall item N+1 next. Both
      experiments reveal more fill-in than infill errors, not only overall but at each
      possible error location throughout the list. The overall ratio is approximately
      2:1. We conclude that none of the currently existing models adequately accounts
      for fill-in and infill errors.

PMID- 15952261
TI  - Capacity limits in list item recognition: evidence from proactive interference.
AB  - Capacity limits in short-term recall were investigated using proactive
      interference (PI) from previous lists in a speeded-recognition task. PI was taken
      to indicate that the target list length surpassed working memory capacity. Unlike
      previous studies, words were presented either concurrently or sequentially and a
      new method was introduced to increase the amount of PI. On average, participants
      retrieved about four items without PI. We suggest an activation-based account of
      capacity limits.

PMID- 15952262
TI  - The relationship between age, processing speed, working memory capacity, and
      language comprehension.
AB  - A total of 50 elderly individuals and 48 college students were tested on several
      measures of processing speed and of working memory capacity. Language processing
      was tested with an on-line measure of sentence processing efficiency, an end-of
      sentence acceptability judgement task, and a paragraph comprehension test.
      Elderly individuals performed more poorly than college students on the speed of
      processing and working memory measures and had longer listening times overall on
      the sentence processing measures. Elderly individuals did not, however, have
      overall longer listening times at the most capacity-demanding regions of the
      harder sentence types. Correlational analyses failed to establish a relationship
      between the increase in syntactic processing load at the capacity-demanding
      region of the harder sentence type and the measures of working memory capacity,
      but did establish a relationship between paragraph comprehension and working
      memory capacity. The data are argued to provide evidence that the WM system used
      to structure sentences syntactically is separate from that used in other aspects
      of language comprehension.

PMID- 15952263
TI  - Not "just" a coincidence: frontal-striatal interactions in working memory and
      interval timing.
AB  - The frontal cortex and basal ganglia play central roles in working memory and in
      the ability to time brief intervals. We outline recent theoretical and empirical
      work to suggest that working memory and interval timing rely not only on the same
      anatomic structures, but also on the same neural representation of a specific
      stimulus. Specifically, cortical neurons may fire in an oscillatory fashion to
      form representations of stimuli, and the striatum (a basal ganglia structure) may
      detect those patterns of cortical firing that occur co-incident to important
      events. Information about stimulus identity can be extracted from which cortical
      neurons are involved in the representation, and information about duration can be
      extracted from their relative phase. The principles derived from these
      biologically based models also fit well with a family of behaviourally based
      models that emphasise the importance of time in many working memory phenomena.

PMID- 15952264
TI  - Stem cell tensions mount.
AB  - The US has been a major battle-ground amongst legislators coming to grips with
      the issue of embryonic stem cell research but the issue is reaching new heights
      in Italy. Nigel Williams reports.

PMID- 15952265
TI  - James W. Valentine.

PMID- 15952266
TI  - Language lateralisation in schizophrenia.

PMID- 15952267
TI  - The independent nurse role in community care gerontological nursing.

PMID- 15952269
TI  - Cognitive-behavioural interventions in schizophrenia.

PMID- 15952268
TI  - Reduction in coagulation factor VII plasma levels by R353Q but not the -323P0/10
      promoter polymorphism in healthy Tunisians.
AB  - The association between the R353Q and -323P0/10 (10-bp insertion in the promoter
      region at position -323) factor VII mutations and plasma factor VII levels was
      investigated in a group of 214 healthy Tunisians. The frequency for the Q allele
      was 0.253 and that for the 10-bp allele was 0.206, and their distribution was
      variable, with a high prevalence of the 10-bp allele (0.306) seen in North
      Tunisia and a high prevalence of the Q allele (0.288) see in the Sahel region. No
      significant linkage disequilibrium was observed between the two mutations, and
      the most prevalent haplotype was -323P0/353R (0.589 +/- 0.054). Carriers of the
      R353Q (P < 0.001), but not -323P0/10 (P = 0.088), factor VII mutations had lower
      mean factor VII serum concentrations. This reduction in mean serum factor VII was
      more pronounced among homozygous (Q/Q) carriers and among males (49.9%) compared
      to females (32.7%). Adjusting for all other variables in the linear regression
      analysis (sex, age, region, smoking, and R353Q and -323P0/10 mutations),
      heterozygous carriers of the -323P0/10 and R353Q mutation had on average
      reductions of 10 units (P = 0.005) and 30 units (P < 0.001) in plasma factor VII,
      respectively, compared to noncarriers, while homozygote carriers of the R353Q (
      43.3, P < 0.001), but not carriers of the -323P0/10 (-6.30, P = 0.356), had
      significantly lower levels of mean plasma factor VII. These data suggest that
      part of the previously described effects on FVIIc levels associated with the R/Q
      polymorphism may be explained by genetic variation in the promoter region of the
      FVII gene.

PMID- 15952270
TI  - Suicide and antidepressants sales.

PMID- 15952271
TI  - The road to evidence: the European path.

PMID- 15952272
TI  - Building the evidence base: from tool development to agenda-setting and defining
      a joint programme for health promotion in Europe.

PMID- 15952273
TI  - The European Region's contribution to the Global Programme on Health Promotion
      Effectiveness (GPHPE).

PMID- 15952274
TI  - Toward European consensus tools for reviewing the evidence and enhancing the
      quality of health promotion practice.

PMID- 15952275
TI  - Evidence-based health promotion practice: how to make it work.

PMID- 15952276
TI  - From evidence to practice: mental health promotion effectiveness.

PMID- 15952277
TI  - From evidence to practice: tobacco control effectiveness.

PMID- 15952278
TI  - Mapping European capacity to engage in health promotion at the national level: HP
      Source.net.

PMID- 15952279
TI  - Where are we headed? The next frontier for the evidence of effectiveness in the
      European Region.

PMID- 15952280
TI  - Maladaptive behavioural patterns of early weaned, indoor raised pigs.
AB  - The objective of the present study was to investigate the growth rate and
      maladaptive behaviour of early (day 14 of lactation) or late (day 28 of
      lactation) weaned pigs of either sex kept under different light intensities.
      Maladaptive behaviour was diagnosed when piglets were kept under a high light
      intensity but not when kept under a low light intensity. The time, spent engaged
      in maladaptive behaviour was not higher for barrows than for gilts. Lesions on
      'recipient' animals were more severe in larger pigs with a greater rate of weight
      gain than in smaller ones. 'Perpetrator' pigs grew more slowly during the 46 days
      after weaning (P = 0.0013) than the non-preparator-pigs. 'Recipient' animals were
      significantly heavier and had higher rates of weight gain (P = 0.0003) than the
      'perpetrator' pigs.

PMID- 15952281
TI  - [What will be your answer?].

PMID- 15952282
TI  - [VWA researches bacterial cleaners].

PMID- 15952283
TI  - [Symposium Veterinarians Without Borders Europe].

PMID- 15952284
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Four quarters milking machine].

PMID- 15952285
TI  - [Comparison veterinary professional organization in Europe].

PMID- 15952286
TI  - [Question and answer. Stomach dilatation and torsion in dogs].

PMID- 15952287
TI  - [The art of managing and the future of veterinary education: Management day
      KNMvD, Rhoon, 28 April 2005].

PMID- 15952288
TI  - [Election program cluster 1, committee selection KNMvD 2005].

PMID- 15952289
TI  - [Review supply and demand veterinary jobs September-December 2004].

PMID- 15952290
TI  - [Interview with congress member Niels Groot Nibbelink. 'The KNMvD is more than
      just getting together.' Interview by Susan Umans].

PMID- 15952291
TI  - Emergent biliary drainage for choledochal cyst.
AB  - Two patients with choledochal cyst who needed an emergent biliary drainage are
      presented. Case 1: Spontaneous rupture of the cyst was demonstrated by
      hepatobiliary scintigram in a 21-month-old girl and an emergent T-tube drainage
      relieved her symptom. Acute obstruction by protein plugs was considered to have
      caused rapid expansion of the cyst, which resulted in rupture eventually. Case 2:
      Marked hypoproteinemia was demonstrated in a 29-month-old boy with choledochal
      cyst. Bile drainage through Foley catheter promptly made the serum protein level
      elevated above normal range. Portal hypertension due to severely dilated cyst may
      have increased ascites amount, which caused extracellular fluid shift and protein
      to be lost into ascites. In both cases the excision of the extrahepatic bile duct
      and hepaticojejunostomy was carried out successfully later. Treatment of 20
      pediatric cases in our institute and the literature were reviewed. Bile drainage
      would be safer in emergency condition even though it has been suggested that
      reconstructive surgery may be tolerable. Definitive surgery should be regarded as
      a procedure with some risk of postoperative complications because asymptomatic
      cases operated electively had serious ones. Treatment strategy of patients with
      choledochal cyst is not straightforward and should be arranged based upon their
      conditions.

PMID- 15952292
TI  - Development of a new mouth opening force test using an indirect cervical traction
      device.
AB  - BACKGROUND AND AIMS: There have been few reports of objective jaw opening tests,
      and such studies have involved devices specifically designed for research. In the
      present study, in order to conveniently and objectively assess mouth opening
      movements, we replaced the manual resistance used in Daniels and Worthingham's
      muscle test (DMT) with an indirect cervical traction device. We examined whether
      the maximum mouth opening force (MOF) could be reliably quantified using this
      device. METHODS: The subjects were 12 healthy individuals with a mean age of 28.8
      years. The MOF measurement procedure was as follows: 1) the subject sat in the
      chair, and a head belt was placed under the chin so that a traction force was
      applied almost parallel to the body axis; 2) the researcher instructed the
      subject to maintain the maximum mouth opening; 3) as maximum resistance was
      approached, the rate of increase in the traction force decreased. Maximum opening
      force was recorded; 4) one measurement was taken per session, for a total of two
      measurements per subject. Pearson's correlation coefficients were used to assess
      the reproducibility of MOF values. RESULTS: The average MOF (mean +/- SD) in the
      first and second tests was 24.2 +/- 1.9 and 24.5 +/- 2.0 kg. There was an
      extremely high correlation between first and second measurements (r = 0.969).
      CONCLUSIONS: The presently described indirect cervical traction device can be
      used to reliably quantify MOF.

PMID- 15952293
TI  - The 23 gauge capsulorrhexis forceps having a cystotome function.
AB  - We evaluate the operational performance of the 23 gauge capsulorrhexis forceps
      with a cystotome function. The 23 gauge capsulorrhexis forceps were applied in 6
      complex cases such as cataract surgery after closed-angle glaucoma with shallow
      anterior chamber, mal mydriasis, or lens subluxation. In all cases, we measured
      each patient's gonio angle level and degree of mydriasis. The forceps can be used
      in all cases even shallow anterior chamber glaucoma, because the forceps have
      both the functions of forceps and a cystotome with 55 degrees angulated needle.
      Although lens subluxation was found in 5 out of the 6 cases during continuous
      curvi-linear capsulorrhexis (CCC), implantation of the intraocular lens (IOL) in
      the capsular bag was successfully completed in these 5 cases. The 23 gauge
      forceps were effective particularly in cases for cataract surgery after glaucoma
      operation.

PMID- 15952294
TI  - An analysis of the chest wall motions using the dynamic MRI in healthy elder
      subjects.
AB  - The objective of this study was to compare respiratory motions of the chest wall
      in the healthy elder subjects (N = 5; mean age, 71 years old) with those in
      healthy young subjects (n = 9; mean age, 29 years old). Thirty sequential images
      (scanning time, 0.4s per image) of dynamic MRI on sagittal and coronal planes
      were obtained while the subjects were deeply breathing. Lung volume change was
      simultaneously measured with pneumotachometer. In the elder subjects, dimensions
      of the middle and posterior parts of the diaphragm were linearly related to
      instantaneous lung volume. There were poor correlation between motion of the
      anterior diaphragm and transverse motions of the upper rib-cage and lower rib
      cage. The contribution of individual part of the chest wall motion to a unit lung
      volume change, assessed by slope of the linear regression line, in elder subjects
      were not significantly different from those in young subjects. Either in the
      elder or young subjects, the middle and posterior parts of the diaphragm moved
      coordinately. We conclude that chest wall motion in the healthy elder subjects is
      not different from that in healthy young people and that middle and posterior
      parts of the diaphragm act as one functional unit during deep breathing.

PMID- 15952295
TI  - MRI tracer study of the cerebrospinal fluid drainage pathway in normal and
      hydrocephalic guinea pig brain.
AB  - OBJECTIVE: Using magnetic resonance imaging (MRI), sequential information
      regarding the dynamic movement of the cerebrospinal fluid (CSF) from the
      subarachnoid space and the ventricles to the drainage pathway in response to the
      CSF pressure was obtained in guinea pigs. In this study, a new mechanical
      hydrocephalus model in a guinea pig was developed to investigate the CSF kinetics
      in an acute hydrocephalic brain. MATERIALS AND METHODS: A total of 18 adult male
      guinea pigs were studied. In the ventricular injection group, The CSF in the
      lateral and third ventricles was isolated by inserting a polyethylene tube with a
      cotton ball into the aqueduct of Sylvius. By infusing artificial CSF through this
      tubing acute ventriculomegaly was created. In the subarachnoid injection group, a
      polyethylene tube was placed at the cisterna magna. Using MRI with gadoteridol as
      a tracer, the movement of CSF from the subarachnoid space and dilated ventricles
      was monitored at various pressures. The CSF drainage pathway from the
      subarachnoid space in the hydrocephalic condition was examined and compared with
      the CSF drainage pathway in normal condition. RESULTS: Gadoteridol cleared from
      the lateral and third ventricles and reached the nasal mucosa via brain
      parenchyma; the movement was proportional to the CSF pressure. Gadoteridol from
      the subarachnoid space also reached the nasal mucosa and periorbital region in a
      similar manner. However, it was not observed to reach either over the convexity
      of the brain or adjacent to the superior sagittal sinus.

PMID- 15952296
TI  - Hepatocellular carcinoma with metastasis to the pharynx: report of a case.
AB  - Hepatocellular carcinoma (HCC) is rarely metastasized to the pharyngeal region.
      We report the case of a 59-year-old man admitted to our hospital with a complaint
      of hematemesis. An endoscopic examination revealed a tumor located in the left
      piriform sinus. Histological examination showed metastasis from HCC. Subsequent
      abdominal examinations demonstrated mild liver cirrhosis due to chronic HCV
      infection and primary nodules in the lateral segment of the liver. The pharyngeal
      tumor was completely removed by endoscopic polypectomy after radical hepatectomy
      for HCC. The patient died of recurrence of HCC 8 months after the first
      admission. With the presentation of this case, we review the literature reported
      so far.

PMID- 15952297
TI  - A pheochromocytoma causing limited coagulopathy with hemoptysis.
AB  - We treated a 59-year-old woman presenting with hemoptysis, a rare symptom of
      pheochromocytoma. Multiple factors including hypertension caused by sudden
      catecholamine release may result in pulmonary edema. It should be noted that the
      increased activation of coagulation cascade, which was demonstrated by increased
      thrombin-antithrombin III complex (TAT) and prothrombin fragment factor 1 and 2
      (F1 + 2), as well as endothelial or platelet stimulation evidenced by the
      increased plasma von Willebrand factor, may have contributed to hemoptysis. These
      abnormalities were normalized after adrenalectomy. Our case indicates the
      important role of catecholamine in coagulopathy and possibly in vasculopathy.

PMID- 15952298
TI  - Platelet activation in patients with alcoholic liver disease.
AB  - OBJECTIVE: To elucidate the mechanisms of thrombocytopenia in alcoholic liver
      diseases, we investigated activation status of platelets in patients with
      alcoholic fatty liver (Al-FL), alcoholic liver cirrhosis (Al-LC) or hepatitis-C
      liver cirrhosis C (C-LC). METHODS: Platelet activation was evaluated by flow
      cytometry using monoclonal antibodies against P-selectin (CD62P) and the
      fibrinogen receptor (PAC-1), both specific for platelet activation, and anti-CD61
      antibody for the presence of microparticles (PMP) in seven patients with Al-FL,
      thirteen patients with Al-LC and, as a non-alcoholic liver disease control, nine
      patients with C-LC. As a normal control, seventeen healthy subjects without liver
      dysfunction were also evaluated. RESULTS: Compared with the healthy controls, the
      platelet count was significantly decreased in patients with alcoholic liver
      diseases or C-LC. Ten days after discontinuation of alcohol intake, the platelet
      count was significantly higher in both the Al-FL and Al-LC groups than that
      measured on admission. There was an inverse correlation between the platelet
      count and PMP, a marker of platelet activation. The Al-FL, Al-LC and C-LC groups
      showed significantly higher percentages of platelets positive for CD62P than the
      healthy controls. The PAC-1 positivity was increased only in the C-LC group. PMP
      were significantly increased in the Al-FL, Al-LC and C-LC groups compared to that
      in the healthy group. In the Al-LC group, PMP were significantly decreased 10
      days after discontinuation of alcohol intake from that measured on admission.
      CONCLUSION: Patients with alcoholic liver diseases have increased platelet
      activation, which may contribute to the occurrence of thrombocytopenia. The
      formation of PMP might be one of the important factors of thrombocytopenia in
      alcoholic liver diseases.

PMID- 15952299
TI  - Evaluation of applied cases of thrombolytic therapy against ultra-acute ischemic
      stroke. Using the Japanese Standard Stroke Registry Database.
AB  - BACKGROUND: A retrospective evaluation was made concerning thrombolytic therapy
      for ultra-acute ischemic stroke patients, using a recombinant tissue plasminogen
      activator (rt-PA), which is not yet approved as a drug for brain infarction in
      Japan. The evaluation was implemented using the database of patients that
      suffered acute strokes as collected by the Japanese Standard Stroke Registry
      Study (JSSRS). METHODS: The thrombolytic therapy group, selected from among the
      registered 6,090 cases of brain infarction patients, was divided into two groups,
      namely, a group of patients who were admitted in the hospital within 3 hours of
      the onset (86 cases, average age 69.6) and the other group who were admitted
      after 3 hours from the onset (28 cases, average age 66.8). Using a Multiple
      Logistic Regression Analysis adapted for modified Rankin scale (mRS) regarding
      each group, the clinical effects of thrombolytic therapy for functional outcome
      and presence or absence of dementia at the time of hospital discharge were
      examined. Among the 467 cases of patients (average age 74) who were admitted
      within 3 hours of the onset and for whom the NIH Stroke Scale (NIHSS) was between
      6 and 29 at the time of admission, intravenous or intra-arterial thrombolytic
      therapy was conducted in 88 cases. Then, a case-control study and Multiple
      Logistic Regression Analysis was implemented for subject groups matched according
      to the gender, age and severity at the time of admission, and the effects on
      early-admitted patients were examined. Also, for two rehabilitation patient
      groups: one whose rehabilitation started within 7 days (216 cases; average age
      73) and the other whose rehabilitation started after 7 days (56 cases, average
      age 76), the effects of early rehabilitation were examined using Multiple
      Logistic Regression Analysis. Moreover, the effects of thrombolytic therapy on a
      group of patients who were admitted early and for whom rehabilitation started
      early (215 cases; average age 73) were examined in the same way. RESULTS: In the
      comparison between the thrombolytic therapy groups, the functional outcome of the
      group of patients admitted within 3 hours of the onset at the time of discharge
      (mRS 0-1) was significantly better compared with that of the group after 3 hours
      from the onset (OR 2.79, 95% CI: 1.06-7.32). Regarding the comparison between the
      early admitted patients, the frequency of poor functional outcomes (mRS 2-6) at
      the time of discharge was significantly lower in the thrombolytic therapy group
      (OR 0.55, 95% CI 0.31-0.98), and the frequency of dementia was also significantly
      lower (OR 0.37, 95% CI 0.17-0.86). In the case control study, a significant
      difference was noted for the presence of dementia. In the group rehabilitation
      was started early, the frequency of poor functional outcomes was significantly
      lower (OR 0.33, 95% CI 0.11-0.98), and the frequency of dementia was also
      significantly lower (OR 0.41, 95% CI 0.19-0.89). As for the comparison of the
      groups admitted early and for which rehabilitation started early, the frequency
      of poor functional outcomes at the time of discharge was significantly lower in
      the thrombolytic therapy group (OR 0.38, 95% CI 0.16-0.86). CONCLUSIONS: From the
      present analysis, in spite of being a retrospective analysis based on
      comparatively small number of patient cases from the stroke database, it is
      concluded that the clinical application of thrombolytic therapy for ultra-acute
      ischemic strokes was effective. Moreover, it was demonstrated that, if it is
      possible to start rehabilitation early, a dramatic improvement of the effects
      might be expected.

PMID- 15952300
TI  - Effect of anticholesterol therapy on soluble ICAM-1 in chronic stroke patients
      with hyperlipidemia.
AB  - OBJECTIVE: We examined the effects of drug therapy with pravastatin (P) or
      bezafibrate (B) and diet (D) therapy on serum lipids and soluble intercellular
      adhesion molecule-1 (sICAM-1) in hyperlipidemic cerebrovascular disease (CVD)
      patients in the chronic stage. METHODS: This study included 36 patients (28 with
      cerebral infarction and hyperlipidemia and eight with cerebral hemorrhage and
      hyperlipidemia) divided into three groups: Group P (12 patients), Group B (10
      patients), and Group D (14 patients). Before and after treatment, total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG),
      high density lipoprotein cholesterol (HDL-C) and sICAM-1 levels were measured.
      RESULTS: In Group P, Group B and Group D, TC levels were decreased by 30% (p <
      0.005), 21% (p < 0.01), and 21% (p < 0.001), LDL-C levels were decreased by 38%
      (p < 0.005), 18% (not significant), and 25% (p < 0.005) and TG levels were
      decreased by 27% (p < 0.05), 53% (p < 0.005) and 22% (p < 0.05), respectively.
      sICAM-1 levels were decreased by 20% (p < 0.005) in Group P, but were not
      decreased in Group B or Group D. There was no correlation between deltaTC and
      delta sICAM-1 (r = 0.172). CONCLUSION: Administration of pravastatin
      significantly reduced sICAM-1 levels, independently of its decreasing effect on
      TC and TG in chronic CVD patients. Pravastatin may exert anti-atherosclerotic
      activity via two distinct mechanisms.

PMID- 15952301
TI  - Fatal adenovirus infection indistinguishable from thrombotic microangiopathy
      after allogeneic CD34+ peripheral progenitor cell transplantation.
AB  - A 10-year-old boy with acute lymphoblastic leukemia in second relapse received
      CD34+ purified allogeneic peripheral blood stem cell transplantation (PBSCT) from
      his HLA-haploidentical father. The patient developed grade II acute GVHD and
      received high-dose methyl-prednisolone starting on day + 13 posttransplant. Renal
      dysfunction followed by massive gastrointestinal bleeding was observed from day +
      14. The laboratory findings including elevated serum LDH, increased RBC
      fragmentation, higher level of thrombomodulin and undetectable haptoglobin
      corresponded with the diagnosis of thrombotic microangiopathy (TMA). In spite of
      various treatments, the patient died of multiple organ failure on day + 93. Post
      mortem examination revealed systemic adenovirus infection without histological
      findings of TMA. Severe adenovirus infection may be confused with TMA, and should
      be distinguished by rapid virological assay.

PMID- 15952302
TI  - Secondary G-CSF mobilized blood stem cell transplantation without preconditioning
      in a patient with Gaucher disease: Report of a new approach which resulted in
      complete reversal of severe skeletal involvement.
AB  - Gaucher disease has been treated by allogeneic bone marrow transplantation (BMT),
      however, severe bone involvement that is probably the most disabling aspect of
      this disease is difficult to reverse. Other problem of BMT is the use of
      intensive preconditioning that adversely affects growth and development of the
      patients. In this study, a patient with type I Gaucher disease was treated by
      allogeneic BMT from HLA-matched sibling donor. However, the treatment resulted in
      late graft failure and the patient developed severe bone involvement. Fifty
      months after the first BMT, the patient was treated by allogeneic peripheral
      blood stem cell (PBSC) transplantation without preconditioning. Recombinant human
      granulocyte-colony stimulating factor (rhG-CSF) was used to mobilize PBSC.
      Cyclosporine A (CyA) was administered for the prophylaxis of graft-versushost
      disease (GVHD). Full donor-derived hematopoiesis was obtained, and clinical
      symptoms including severe bone involvement improved completely with increased
      glucocerebrosidase activity. It was shown that an engraftment could be obtained
      without intensive preconditioning when a recipient receives an rhG-CSF-mobilized
      PBSCs infusion as a secondary transplant. Another important finding of this study
      is the complete reversal of severe bone involvement by the supply of abundant
      glucocerebrosidase from high proliferating PBSC graft.

PMID- 15952303
TI  - [Genetic analysis and individualized therapy for diffuse glioma].

PMID- 15952305
TI  - [Assessment of the perianeurysmal environment of unruptured internal carotid
      posterior communicating artery aneurysms with fusion imaging of three-dimensional
      magnetic resonance cisternography and angiography].
AB  - The anatomical relationship of an unruptured internal carotid-posterior
      communicating artery aneurysm and the perianeurysmal environment was investigated
      by using three-dimensional (3D) magnetic resonance cisternography (MRC),
      angiography (MRA) and newly developed fusion images of 3D MRC and 3D MRA. Contact
      of an aneurysm with the adjacent intra- and pericisternal structures was observed
      in cases with the aneurysm developing and extending beyond the capacity of the
      surrounding subarachnoid space. Deformation and bleb formation of the aneurysmal
      dome was depicted at the dome in contact with the perianeurysmal environment,
      including the tentorial edge, the anterior petroclinoid dural fold, the
      oculomotor nerve, the posterior clinoid process, the dorsum sellae and the
      cranial base bone. By using the fusion imaging technique of 3D MRC and 3D MRA,
      assessment of the contact of an unruptured cerebral aneurysm with its
      perianeurysmal environment can be made. Such contact gives ride to risk of
      deformation and bleb formation of the aneurysmal dome; and may result in cranial
      nerve symptoms and accelerate rupture from an unruptured cerebral aneurysm.

PMID- 15952306
TI  - [Reinvestigation of CSF outflow resistance value in idiopathic normal pressure
      hydrocephalus--comparing epidural pressure monitoring with lumbar subarachnoid
      cerebrospinal fluid pressure monitoring].
AB  - PURPOSE: To compare the cerebrospinal fluid (CSF) outflow resistance values (Ro)
      with epidural pressure (EDP) monitoring and lumbar subarachnoid CSF pressure (L
      CSFP) monitoring. SUBJECTS AND METHODS: The subjects were 14 patients with
      possible iNPH (age: 59-74 years old, ratio of male and female 8:6). All the
      patients were subjected to an infusion test by a single bolus injection method (1
      ml/sec., deltaV: 5 ml, t2: 2 min) as prescribed in the Standard of SINPHONI. EDP
      was monitored by continuous monitoring and the L-CSFP values By intermittent
      simple glass tube method (SINPHONI) were measured simultaneously. The Ro (RoEDP,
      RoL-CSFP) calculated from both methods, (1) the correlation of Ro and (2) the Ro
      threshold in a shunt effective group (E: nine cases) and a non effective group
      (NE, five cases) were compared. RESULTS: (1) Although a favorable correlation was
      found between both Ro measurements (r=0.784), the RoEDP was always higher than
      the RoL-CSFP. (2) The mean Ro values in the E and NE groups were 36.8 +/- 15.7
      mmHg/ml/min, and 10 +/- 2.05 mmHg/ml/min for Ro-EDP, 22.1 +/- 13.95 mmg/ml/min
      and 6.4 +/- 1.7 mmHg/ml/min for RoL-CSFP, respectively. The approximate
      thresholds in the E and NE groups were 15 mmHg/ml/min for RoEDP and 10
      mmHg/ml/min for RoL-CSFP. CONCLUSION: (1) Although the RoEDP is always higher
      than the RoL-CSFP, a favorable correlation is found between the RoEDP and RoL
      CSFP, (2) The Ro thresholds of the E and NE groups in the infusion test are about
      15 mmHg/ml/min for RoEDP and 10 mmHg/ml/min for RoL-CSFP. (3) After this, Ro
      calculation ought to execute by standard of SINPHONI and the Ro threshold of the
      E and NE groups is about 10 mmHg/ml/min.

PMID- 15952307
TI  - [Flow reverse therapy for ruptured dissecting aneurysm of basilar trunk: case
      report].
AB  - Treatment of ruptured dissecting aneurysm of basilar trunk (BADAN) has been
      controversial yet. We report a case of ruptured BADAN successfully treated with
      endovascular occlusion of the bilateral vertebral artery (VA) proximal to
      posterior inferior cerebellar artery (PICA), allowing retrograde flow via the
      posterior communicating arteries to basilar artery. A 58-year-old woman who had
      subarachnoid hemorrhage was treated with endovascular occlusion of the right VA
      in acute stage after ballon occlusion test (BOT) of the right VA. Because
      following BOT of the left VA showed conscious level down, left VA could not be
      occluded. Follow-up angiography after 26 days revealed regrowth of BADAN. So left
      VA occlusion was tolerable by BOT after 1 month, we performed endovascular
      occlusion of the left VA proximal to PICA. She discharged with no neurological
      deficit after 3 months. Postoperative angiograms 3 months after onset showed
      complete healing of the aneurysm. The follow-up MRA at 19 months showed no
      recurrence. We discussed the therapeutic strategy of ruptured BADAN. Flow reverse
      therapy of bilateral VA occlusion by endovascular method for ruptured BADAN is
      one of the effective therapy.

PMID- 15952308
TI  - [Pachymeningoencephalitis: case report].
AB  - A 59-year-old man presented with generalized convulsion. MR imaging demonstrated
      a homogeneously enhanced dural lesion infiltrating the parenchyma in the right
      parietal region. He had no history of sinusitis and the lesion a resembled
      malignant tumors, so surgical treatment was performed. The histopathological
      studies showed pachymeningitis extending to the cerebral parenchyma, so the
      diagnosis of pachymeningoencephalitis was made. After the operation, the patient
      had no neurological deficits and anticonvulsant therapy was continued. We report
      the third case of idiopathic local pachymenigoencephalitis that we could range
      extensively in the world. The clinical features and pathogenesis are discussed.

PMID- 15952309
TI  - [Subfrontal schwannoma: case report].
AB  - Schwannoma are benign, slowly growing nerve sheath tumors. They can arise from
      any peripheral nerve containing Schwann cells including distal portions of
      cranial nerves. Intracranial schwannomas arising from a subfrontal lesion are
      very rare. We report a case of subfrontal schwannoma in a 38-year-old woman who
      presented with seizures in February 2003. MRI features resembled an olfactory
      groove meningioma. The left carotid angiography revealed that the tumor was
      supplied from the anterior ethomoidal artery, but no remarkable tumor stain was
      detected. Bifrontal craniotomy with total excision of the tumor revealed a tumor
      in the left subfrontal lesion. The tumor was attached to the falx, the left
      frontal lobe, and the skull base, but those structures were not invaded.
      Unfortunately, we could not detect the left olfactory nerve. Subsequent
      histological examination proved that this tumor was schwannoma. A review of the
      literature found 27 cases including this case previously described. Arguments are
      raised that schwannomas in a subfrontal lesion are comparable to or even occur as
      intracranial schwannomas with frontal localization. Subfrontal schwannomas are
      very rare. For this reason they have not been diagnosed preoperatively. Further
      cases of subfrontal schwannoma are necessary to solve the enigma of the origin of
      this tumor.

PMID- 15952310
TI  - [Pneumocephalus caused by failed ventricular tap: case report].
AB  - OBJECTIVE AND IMPORTANCE: Ventricular tap is one of the most basic and important
      techniques to neurosurgeon. Brain tap itself usually does not cause symptomatic
      complication. The authors report an extremely rare complication case of
      pneumocephalus caused by failed ventricular tap. CLINICAL PRESENTATION AND
      INTERVENTION: A 79-year-old woman suffered from normal pressure hydrocephalus
      after subarachnoid hemorrhage (SAH). Ventriculo-peritoneal shunt was performed
      two month after SAH. In the operation, ventricular taps were failed twice and
      third tap was successful for ventricular catheterization through the right
      posterior parietal burr hole. She presented left hemiparesis from three hours
      after the operation, and her symptom was gradually deteriorated to complete
      paralysis the next day. Computed tomography scan disclosed the movement of air
      along the tract of failed ventricular tap from subcortex to internal capsule.
      CONCLUSION: Failed ventricular tap could cause severe complications. We have to
      try to perform ventricular tap by only one attempt.

PMID- 15952311
TI  - [Aplasia of the right internal carotid artery presenting with callosal
      hemorrhage: case report and review of the literature].
AB  - A 73-year-old woman without a history of cerebral ischemia suffered from sudden
      onset headache. Brain computed tomography (CT) showed intracerebral hemorrhage in
      the corpus callosum with intraventricular hemorrhage and thin subarachnoid
      hemorrhage in the basal cistern. Cerebral angiography showed narrowing of the
      right internal carotid artery just distal to its origin in the neck and abrupt
      occlusion just after branching of the ophthalmic artery with moyamoya-like
      vessels. The right A2 segment showed irregular dilatation and stenosis. The right
      middle cerebral artery was supplied from the basilar artery via the right
      posterior communicating artery. There was neither aneurysm nor arteriovenous
      malformation. Thin-slice bone-window CT of the skull base revealed hypoplasia of
      the right carotid canal. Aplasia of the right internal carotid artery was
      diagnosed. The origin of the hemorrhage was thought to be the irregularly
      opacified right A2 segment, which had been subjected to long-standing hemodynamic
      stress as collateral vessel.

PMID- 15952312
TI  - [Local intraarterial fibrinolysis in central retinal artery occlusion: case
      report].
AB  - The authors report a case of local intraarterial fibrinolysis (LIF) in central
      retinal artery occlusion (CRAO). A 79-year-old man with stenosis of the left
      internal carotid artery (ICA) suffered sudden loss of vision in his left eye. LIF
      was carried out using a microcatheter in the origin of the ophthalmic artery on
      the side of the CRAO. Treatment was performed with 120,000 IU of urokinase. After
      LIF, marked improvement of vision was established. No complication occurred
      during LIF. One month later, carotid artery stenting was performed for the left
      ICA stenosis. We consider LIF in CRAO is effective treatment.

PMID- 15952313
TI  - Quo vadis, esophageal surgery?

PMID- 15952314
TI  - Perioperative rehabilitation and physiotherapy for lung cancer patients with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of pulmonary
      rehabilitation on surgical morbidity and lung function in lung cancer patients
      with chronic obstructive pulmonary disease (COPD). METHODS: Prospectively, 22
      lung cancer patients with COPD who underwent lobectomy between 2000 and 2003 were
      enrolled for this study as a rehabilitation group (Rehab. Group). The criteria of
      COPD were preoperative forced expiratory volume in 1 second (FEV1)/forced vital
      capacity (FVC) < or =70% and more than 50% of low attenuation area in a computed
      tomography. Preoperatively patients performed aggressive pulmonary exercise for
      two weeks and received chest physiotherapy postoperatively. As a historical
      control, 60 patients with lung cancer who fulfilled the same criteria but did not
      receive rehabilitation between 1995 and 1999 (control group) were entered in this
      study. RESULTS: Patient backgrounds were all equivalent between the two groups.
      However, FEV1 and FEV1/FVC were significantly lower in the Rehab. Group (p <
      0.05). Prolonged oxygen supplement and tracheostomy tended to be more frequent in
      the control group. The ratio of actual postoperative to predicted postoperative
      FEV1 was significantly better in the Rehab. Group (p = 0.047). Furthermore,
      postoperative hospital stay was significantly longer in the control group (p =
      0.0003). CONCLUSION: Despite lower FEV1 and FEV1/FVC in the Rehab. Group,
      postoperative pulmonary complications and long hospital stay could be effectively
      prevented and FEV1 was well preserved by rehabilitation and physiotherapy.

PMID- 15952315
TI  - Early results of off-pump coronary artery bypass: retrospective consecutive
      comparative study.
AB  - OBJECTIVE: The purpose of this study is to compare the operative results of off
      pump coronary artery bypass (OPCAB) and on-pump (conventional) coronary artery
      bypass (CCAB), to clarify qualitative problems and whether OPCAB is less invasive
      or not. METHODS: OPCAB was consecutively performed in 63 patients and CCAB in 63
      patients between July 1998 and December 2003. RESULTS: The mean number of bypass
      grafts was 2.43 +/- 0.82 in the OPCAB group and 2.70 +/- 0.71 in the CCAB group
      (p = 0.096). In-hospital mortality was 0% in the OPCAB group and 3.2% in the CCAB
      group. The incidence of perioperative myocardial infarction was 0% in the OPCAB
      group and 3.2% in the CCAB group. The incidence of postoperative major
      complications was significantly lower in the OPCAB group than in the CCAB group
      (OPCAB group=4 complications, CCAB group=13 complications). Cerebrovascular
      accidents occurred in 1.6% of patients in both groups. The incidence of sternal
      infection or mediastinitis was 0% in the OPCAB group and 3.2% in the CCAB group.
      The early patency rate of graft was 94.0% in the OPCAB group and 92.8% in the
      CCAB group, and was not significantly different (p = 0.822). CONCLUSION:
      Operative mortality and major complications after surgery in OPCAB were lower
      than that in CCAB. The early patency rate in OPCAB was as good as that in CCAB.
      It is considered that OPCAB is less invasive and the quality of bypass in OPCAB
      is as good as that in CCAB.

PMID- 15952316
TI  - Cognitive dysfunction following cardiovascular surgery.
AB  - OBJECTIVE: The aim of this study was the evaluation of perioperative cognitive
      dysfunction in patients undergoing cardiovascular surgery with or without
      cardiopulmonary bypass (CPB) and identification of the risk factors. SUBJECTS AND
      METHODS: Between July 2001 and October 2003, we performed cognitive examinations
      in 192 patients (mean age 65.5 +/- 7.6 years) who underwent elective
      cardiovascular surgery with or without CPB. The cognitive examinations (Hasegawa
      dementia scale) were done both pre- and postoperatively. Forty-six patients who
      had developed cognitive dysfunction postoperatively were included in Group A. The
      remaining 146 patients were placed in the control group (Group B). RESULTS: The
      patients in Group A were noted to be significantly older than those in Group B
      (69.8 +/- 7.4 vs. 64.1 +/- 7.2, p < 0.05). The number of patients who at risk for
      cerebrovascular disease was significantly higher in Group A than in Group B (p <
      0.05). Among intraoperative variables, there were no significant differences
      between the two groups concerning the presence or absence of CPB, CPB duration,
      and operation duration. The length of postoperative hospitalization of the Group
      A patients was greater. Age was identified as the only predictor of postoperative
      cognitive dysfunction in multivariate analysis. CONCLUSION: In the present study,
      it is possible that CPB did not play a significant role in the genesis of
      cognitive dysfunction after cardiovascular surgery. Age appears to be the only
      significant predictor of postoperative cognitive dysfunction.

PMID- 15952317
TI  - Kommerell's diverticular rupture complicated by aberrant left subclavian artery
      and right aortic arch successfully treated surgically.
AB  - We report a rare case of a rupture in Kommerell's diverticulum in a 73-year-old
      woman with Edwards IIIB aberrant left subclavian artery (A-LSA) and right aortic
      arch. This case was further complicated by an inferior vena cava defect. We
      performed an emergency operation through a right posterolateral approach. The
      descending aorta was replaced and the Kommerell's diverticulum was excised,
      followed by A-LSA reconstruction, performed under deep hypothermia with selective
      cerebral perfusion. We believe the prognosis was excellent.

PMID- 15952318
TI  - Successful repair of traumatic tricuspid valve regurgitation.
AB  - Isolated traumatic tricuspid valve regurgitation is an uncommon complication of
      blunt chest trauma. Tricuspid valve replacement has been ordinarily managed for
      this lesion. Herein, we report two cases of successful repair for traumatic
      tricuspid valve regurgitation, 11 and 40 years following blunt chest trauma,
      respectively. Tricuspid valve repairs were performed using an artificial chordae
      implantation with expanded polytetrafluoroethylene (CV-5) sutures and ring
      annuloplasty. Postoperative echocardiography revealed that the tricuspid valve
      regurgitation improved to mild and trivial respectively in two patients. They are
      presently doing well, 4 and 2 years after the repair, respectively.

PMID- 15952319
TI  - Basaloid carcinoma of the lung.
AB  - Basaloid carcinoma (BC) of the lung is a rare and an aggressive subtype of non
      small cell lung cancer. We report a patient with preoperative cytologic features
      of either lung BC or squamous cell carcinoma. Finally, the tumor was diagnosed as
      a pure BC of the lung by the immunohistological findings. The patient's recovery
      was uneventful and remained asymptomatic without recurrence 18 months after
      surgery. However, considering to the biological behavior of BC, regular follow-up
      for this patient will be required.

PMID- 15952320
TI  - Metastatic somatostatinoma of the chest wall.
AB  - A 72-year-old male was diagnosed as having a thoracic tumor in the left chest
      wall five years after resection of primary pancreatic somatostatinoma. The tumor
      was suggestive of metastasis to the chest wall or to the left lung from the
      previously resected somatostatinoma based on the abnormally elevated serum
      somatostatin level. Percutaneous biopsy confirmed that the lesion was an islet
      cell tumor and thoracotomy demonstrated metastasis to the left third rib without
      involvement of the left lung. Our case represents a rare documentation of
      somatostatinoma metastatic to the chest wall for which complete resection was
      performed.

PMID- 15952321
TI  - Pedicled cardiac hemangioma with right ventricular outflow tract obstruction.
AB  - A 46-year-old female was admitted to our hospital complaining of dizziness.
      Echocardiography and magnetic resonance imaging showed a pedicled tumor in the
      right ventricular outflow tract (RVOT), causing severe obstruction during
      systole. Resection was performed under cardiopulmonary bypass. Postoperative
      course was uneventful, with complete disappearance of major symptoms.
      Histological examination revealed the nature of the tumor to be a benign
      hemangioma. As reports of cardiac hemangioma causing severe RVOT obstruction are
      extremely rare, this case warrants attention.

PMID- 15952322
TI  - Rare complication of dissection of Valsalva sinus with aorto-left atrial fistula
      in active aortic valve endocarditis.
AB  - We present a rare case of dissection of the sinus of Valsalva associated with an
      aortic annular abscess that perforated into the left atrium. A 61-year-old
      patient with infective endocarditis underwent emergent operation due to
      progressive heart failure, in whom echocardiography showed the dissection of
      sinus of Valsalva with aorto-left atrial communication. Procedure included
      autologous pericardial patch repair of the dissecting sinus of Valsalva and
      bioprosthetic valve replacement with a successful outcome. Microscopic
      examination showed excessive neutrophil infiltration in the aortic valve and
      annulus without involvement of the sinus of Valsalva.

PMID- 15952323
TI  - Malignant fibrous histiocytoma of the trachea.
AB  - We experienced a rare case of malignant fibrous histiocytoma (MFH) arising in the
      trachea. A 24-year-old man with severe dyspnea had a well-defined mass in the
      cervical trachea on chest X-ray examination. Chest computed tomography showed a
      2.0-cm diameter mass originating in the right-posterior wall of the trachea. The
      tumor occupied over 90% of the lumen. A radical excision of the tumor (tracheal
      resection) with tracheal plasty was performed. The microscopic diagnosis was MFH.
      The patient remains well, without evidence of recurrence, 3 months after surgery.

PMID- 15952324
TI  - Catamenial pneumothorax in a pregnant patient.
AB  - We report the case of a 29-year-old woman who experienced recurrence of
      catamenial pneumothorax during pregnancy. Pneumothorax unrelated to the hormonal
      cycle occurred by pulmonary endometriosis. Thoracoscopic resection of cystic
      lesions and pleurodesis effectively controlled the pneumothorax.

PMID- 15952325
TI  - Double right coronary artery; fistula and atherosclerosis: rare combination.
AB  - Combination of the primary congenital coronary artery anomalies, fistula and
      atherosclerosis rarely occur. We report a 50-year-old male who presented with
      severe chest pain, for which he underwent a coronary angiography. Injection into
      the right coronary artery (RCA) demonstrated a double RCA running very closely
      together in the atrioventricular groove. The superior one gave rise to a coronary
      fistula leading to the right ventricle and the inferior one was atherosclerotic.
      Both of them terminated as a posterior descending artery. The left system showed
      occlusion of the left anterior descending and major obtuse marginal. Both were
      corrected surgically.

PMID- 15952326
TI  - Mediastinal Castleman disease associated with pulmonary carcinoma, mimicking N2
      stage lung cancer.
AB  - A 67-year-old man presented at our hospital with suspected right lung cancer with
      mediastinal and hilar lymphadenopathy. Although swollen lymph nodes had first
      been noted 8 years previously, only minimal enlargement had occurred over the
      intervening period. Video-assisted thoracoscopic biopsy of the pulmonary lesion
      and the mediastinal and hilar lymph nodes was performed. Final histopathological
      diagnosis was a poorly differentiated adenocarcinoma of the lung staged as T1NOMO
      and a coexistent localized hyaline-vascular type of Castleman disease. Right
      upper lobectomy was performed and postoperative histological findings suggested
      that this was likely to be curative. This is a rare case of coexistence of lung
      cancer and Castleman disease, illustrating the difficulties in distinguishing
      lymph node metastasis from other pulmonary diseases.

PMID- 15952327
TI  - Successful valve repair for congenital bicuspid aortic valve and degenerated
      prolapsed mitral valve.
AB  - A 54-year-old man with congenital bicuspid aortic valve underwent simultaneous
      valve repair for aortic and mitral regurgitation. Surgical technique consisted of
      plication of redundant aortic valve repair and mitral annuloplasty with chordal
      replacement. One-year follow-up transthoracic echocardiography showed no valve
      regurgitation. Valve repair for both bicuspid aortic valve and mitral valve
      regurgitation should be the first option in this subset of patients.

PMID- 15952328
TI  - [Neurodegenerative diseases regulated by ubiquitin-proteasome system].

PMID- 15952329
TI  - [New era of structural analysis of proteins by electron microscopy-application to
      a dynamic structural analysis of integrin cell adhesion receptor-].

PMID- 15952330
TI  - [Regulatory mechanism of melatonin synthesis in pineal gland: regulation of
      serotonin N-acetyltransferase activity].

PMID- 15952331
TI  - [A DNA exchange reaction during meiosis].

PMID- 15952332
TI  - [Biological effects of proinsulin C-peptide].

PMID- 15952333
TI  - [FOXO: the regulator of metabolism, longevity, and aging].

PMID- 15952334
TI  - [Bach2 orchestrates the transcriptional programme of B cell activation].

PMID- 15952335
TI  - [Synaptic adhesion molecules for neuronal circuit assembly].

PMID- 15952336
TI  - [Physiological function of cyclin-dependent kinase 5 in neuron].

PMID- 15952337
TI  - [Regulation of skeletal muscle mass and adipose tissue mass by follistatin and
      follistatin-related gene (FLRG) and development of novel polypeptides as medical
      drugs].

PMID- 15952338
TI  - [Juvenile nasopharyngeal angiofibroma: stage and surgical approach].
AB  - Juvenile nasopharyngeal angiofibromas (JNAs) are benign tumors that occasionally
      invade the pterygopalatine fossa, infratemporal fossa, or middle cranial fossa.
      Several surgical approaches have been used based on the location of the tumor,
      including transpalatal, transmaxillary, and lateral rhinotomy, midfacial
      degloving, and Le Fort type I osteotomy. We reviewed 4 cases of JNA that had been
      treated by resection in the Department of Otolaryngology of Kagoshima City
      Hospital and 31 cases of JNA reported in the Japanese literature between 1990 and
      2003. We analyzed the outcome of the surgical treatment of JNA in these cases to
      identify the surgical approaches that were most effective in removing tumors at
      several different stages. Radkowski staging showed that 17 (48.6%), 2 (5.7%), 4
      (11.4%), 9 (25.7%) and 3 (8.6%) patients had stage IA, IB, IIA, IIC, and IIIA
      tumors, respectively. A transpalatal approach was employed in 11 cases (31.4%), a
      transmaxillary approach in 9 cases (25.7%), a transnasal approach in 6 cases
      (17.1%), and other approaches, (25.7%). The recurrence rate was, 5% in the stage
      I cases, 38% in the stage II cases, and 33% in the stage III cases. The
      transpalatal approach was followed by a high recurrence rate in the cases of
      stage II and higher stage. Several factors are critical when choosing the
      surgical approach to JNA: adequate exposure of the tumor, ability to control
      bleeding, prevention of postoperative facial deformity, and avoidance of
      interference with growth of the face.

PMID- 15952339
TI  - [Identification of sentinel lymph node in neck-node-negative oral and pharyngeal
      carcinoma study of patients, it's feasibility, and problems].
AB  - We assessd the feasibility and problems associated with sentinel lymph node (SLN)
      study in 13 cases of oral and pharyngeal squamous cell carcinoma (SCC) that were
      neck-node-negative clinically. The primary sites were the tongue (n = 10), other
      sites in the oral cavity (n = 2), and the mesopharynx (n = 1). The day before
      surgery, tracer was injected into the submucosa around the tumor, and
      scintigraphic images were acquired 2 hours later. The SLN was identified
      intraoperatively with a handheld gamma probe, and neck dissection, including the
      SLNs, was performed. Radioactivity within the nodes was confirmed with a well
      type scintillation counter, and all resected lymph nodes were histologically
      examined for metastasis. The SLN was identified in every case. There were
      regional lymphnode metastases in 4 cases, and metastasis to the SLNs was present
      in all of 4 cases. Thus, the SLN concept was valid for head and neck SCC,
      sentinel node navigation surgery (SNNS) was thought to be applied in stage NO SCC
      of the head and neck. If SNNS is performed, about 70% of patients do not require
      neck dissection. SNNS is feasible and cost-effective in these cases. We used two
      different tracers: phytate and tin colloid, and found that phytate was more
      useful. To avoid the effects of the shine-through phenomenon, it was thought that
      some directions of lymphoscintigram should be taken. For intraoperative
      identification of the SLNs, care should be taken to the angle of gamma probe. SLN
      study leads to clarify each patient's lymphoid flow mapping, and it is also
      useful to determine the dissection area of selective neck dissection.

PMID- 15952340
TI  - [Systemic effects of intranasal steroid drops in patients with dysosmia].
AB  - PURPOSE: To evaluate the systemic effects of intranasal steroid drops in patients
      with dysosmia. CASES AND METHODS: Intranasal steroid drops were administered for
      12 weeks to 23 patients with dysosmia, and their plasma cortisol and
      adrenocorticotropic hormone (ACTH) values were measured before and after
      treatment. Improvement in dysosmia was judged based on the standerd olfactory
      test and the patients' symptoms. RESULTS: The post-treatment plasma cortisol
      levels ranged from 0.1 to 25.0 microg/dl (5.4 +/- 5.9 microg/dl), and the
      posttreatment plasma ACTH levels ranged from 5.0 to 55.0 pg/ml (13.8 +/- 11.7
      pg/ml). After treatment, the 23 cases were divided into two groups: 14 cases
      (60.9%) with a decline in cortisol and/or ACTH level, and 9 patients (39.1%) with
      normal plasma cortisol and ACTH levels. Improvement in dysosmia was found in 4
      patients (28.6%) in the former group and 4 patients (44.4%) in the latter group.
      The difference in percentage of patients who improved was not significant between
      the groups. CONCLUSIONS: We conclude that the direct topical effect of intranasal
      steroid drops on the olfactory mucosa may have been the principal reason for the
      improvement in the patients' dysosmia.

PMID- 15952341
TI  - [Temporal bone histopathology in a patient suspected of inner ear extension of
      otitis media].
AB  - We report the histopathological findings in the temporal bone of a 30-year-old
      female who died of cervical esophageal carcinoma. The temporal bone sections
      revealed severe bilateral suppurative labyrinthitis and otitis media that
      presumably occurred immediately before her death. Many inflammatory cells were
      present in the middle ear, particularly around the stapes and the round window
      niche. They had also infiltrated the inner ear via the annular ligament of the
      stapes and the round window membrane. Inflammatory cell accumulation was also
      observed in the peri- and endolymphatic spaces, and it was most severe in the
      basal turn. Most of the inner and outer hair cells were preserved, but some had
      degenerated or were missing. Numerous round cells were observed in the modiolus,
      and some of the spiral ganglion cells had degenerated. On the basis of these
      findings, we concluded that bacterial otitis media had extended in to the inner
      ear via the oval window and round window membrane and had resulted in suppurative
      labyrinthitis. These findings are consistent with those of stage II suppurative
      labyrinthitis according to the classification of Schuknecht.

PMID- 15952342
TI  - Budget cuts raise questions about U.S. DOE priorities.

PMID- 15952343
TI  - Environmental programs: liberal arts colleges and interdisciplinary education.

PMID- 15952344
TI  - Sonochemistry in environmental remediation. 1. Combinative and hybrid
      sonophotochemical oxidation processes for the treatment of pollutants in water.
AB  - Sonoprocessing is the utilization of sonic and ultrasonic waves in chemical
      synthesis and processes. It is a new and rapidly growing research field with
      broad applications in environmental engineering, green chemical synthesis, and
      processing. The application of this environmentally benign technique in
      environmental remediation is currently under active research and development.
      Sonochemical oxidation is effective in treating toxic effluents and reducing
      toxicity. However, the ultrasonic treatment is highly energy intensive since
      sonication is relatively inefficient with respect to total input energy and is
      therefore not economically attractive or feasible alone. Hence, sonochemistry has
      not yet received much attention as an alternative for industrial and large-scale
      chemical and environmental processes. One of the most interesting topics in the
      recent advances in sonochemistry is the possibility of double or more excitations
      with ultrasound and other types of energy. The coupling of ultrasound with other
      free energy sources (i.e., UV) or chemical oxidation utilizing H2O2, O3, or
      ferrous ion presents interesting and attractive approaches. Therefore, many
      recent efforts have been devoted to improving the efficiency of sonochemical
      reactions by exploiting the advantages of combinative or hybrid processes
      involving the simultaneous or sequential use of ultrasonic irradiation and other
      advanced oxidation processes, electrochemical processes, and biological
      treatment. This paper provides a critical review of the applications of
      ultrasound in environmental remediation, focusing on recent developments and
      unifying analysis of combinative or hybrid systems, namely, sonophotochemical
      oxidation processes.

PMID- 15952345
TI  - Screening of human antibiotic substances and determination of weekly mass flows
      in five sewage treatment plants in Sweden.
AB  - Twelve antibiotic substances for human use, including trimethoprim and
      representatives of the fluoroquinolone (FQ), sulfonamide (SA), penicillin (PE),
      cephalosporin (CE), nitroimidazole (NI), tetracycline (TC), and macrolide (MA)
      groups, were subjected to a screening study at five Swedish sewage treatment
      plants (STPs) during one week in 2002 and one week in 2003. The analytes were
      extracted from raw sewage water, final effluent, and sludge by solid-phase
      extraction (SPE) or liquid-solid extraction (as appropriate) and then identified
      and quantified by liquid chromatography/tandem mass spectrometry. The
      mostfrequently detected antibiotics in the matrices considered in this study were
      norfloxacin, ofloxacin, ciprofloxacin, trimethoprim, sulfamethoxazole, and
      doxycycline. The other analytes were only detected in a few samples. Analysis of
      the weekly mass flows through each STP showed that FQs were partly eliminated
      from the water during sewage water treatment and the highest amounts of these
      substances were found in sludge. Sulfamethoxazole and trimethoprim were mainly
      found in raw sewage water and final effluent, but these substances had balancing
      mass flows, indicating that they too can withstand sewage water treatment. The
      mass flow patterns for doxycycline were more complex, with high amounts occurring
      in sludge in some cases, suggesting thatthe behavior of this analyte may be more
      strongly influenced by the treatment process and other variables at individual
      STPs. The environmental load (the sum of the amounts in the final effluent and
      sludge) normalized to the number of inhabitants in the catchment area of each
      investigated STP compared with theoretical predictions based on consumption data
      (in parentheses) showed good correlations: norfloxacin, 0.8 (0.9); ofloxacin, 0.3
      (0.2); ciprofloxacin, 1.3 (3.5); sulfamethoxazole, 0.2 (0.4); trimethoprim, 1.1
      (1.0); and doxycycline, 0.7 (0.4) mg per person per week. The results show that
      reasonably accurate predictions of environmental load of these antibiotics can be
      time-effectively derived from consumption data without additional measurements.

PMID- 15952346
TI  - Occurrence of synthetic musk fragrances in marine mammals and sharks from
      Japanese coastal waters.
AB  - In this study, the occurrence of the polycyclic musk fragrances HHCB (1,3,4,6,7,8
      hexahydro-4,6,6,7,8,8-hexamethylcyclopenta[g]-2-benzopyran) and AHTN (7-acetyl
      1,1,3,4,4,6-hexamethyltetrahydeonaphthalene) in marine mammals and sharks
      collected from Japanese coastal waters is reported. HHCB was present in the
      blubbers of all finless porpoises (Neophocaena phocaenoides) analyzed (n = 8), at
      levels ranging from 13 to 149 ng/g on a wet weight basis. A fetus sample of
      finless porpoise contained a notable concentration of HHCB (26 ng/g wet wt),
      suggesting transplacental transfer of this compound. Among 12 tissues and organs
      of a finless porpoise analyzed, the highest HHCB concentration was found in
      blubber, followed by kidney. This indicates that HHCB accumulates in lipid-rich
      tissues in marine mammals, which is similar to the accumulation profiles of
      persistent organochlorines, such as PCBs and DDTs. In general, the residue levels
      of AHTN and nitro musks were low or below the detection limits in finless
      porpoises, implying either less usage in Japan or high metabolic capacity of
      these compounds in this animal. HHCB was also found in the livers of five
      hammerhead sharks (Sphrna lewini) from Japanese coastal waters, at concentrations
      ranging from 16 to 48 ng/g wet wt. Occurrence of HHCB in higher trophic organisms
      strongly suggests that it is less degradable in the environment and accumulates
      in the top predators of marine food chains. This is the first report on the
      accumulation of synthetic musk fragrances in marine mammals and sharks.

PMID- 15952347
TI  - Colloid-facilitated transport of cesium in variably saturated Hanford sediments.
AB  - Radioactive 137Cs has leaked from underground waste tanks into the vadose zone at
      the Hanford Reservation in south-central Washington State. There is concern that
      137Cs, currently located in the vadose zone, can reach the groundwater. In this
      study, we investigated whether, and to what extent, colloidal particles can
      facilitate the transport of 137Cs at Hanford. We used colloidal materials
      isolated from Hanford sediments. Transport experiments were conducted under
      variably saturated, steady-state flow conditions in repacked, 20 cm long Hanford
      sediment columns, with effective water saturations ranging from 0.2 to 1.0.
      Cesium, pre-associated with colloids, was stripped off during transport through
      the sediments. The higher the flow rates, the less Cs was stripped off,
      indicating in part that Cs desorption from carrying colloids was a residence-time
      dependent process. Depending on the flow rate, up to 70% of the initially sorbed
      Cs desorbed from colloidal carriers and was captured in the stationary sediments.
      Less Cs was stripped off colloids under unsaturated than under saturated flow
      conditions at similar flow rates. This phenomenon was likely due to the reduced
      availability of sorption sites for Cs on the sediments as the water content
      decreased and water flow was divided between mobile and immobile regions.

PMID- 15952348
TI  - Unexpected arsenic compounds in low-rank coals.
AB  - Nine low-rank coal samples from three different coal basins (Velenje and Trbovlje
      basins, Slovenia, and Sokolov basin, Czech Republic) were analyzed for their
      elemental composition and the presence of arsenic compounds. Total arsenic
      concentrations in the samples were 1.59-5.77 microg g(-1) with one exception, 142
      microg g(-1) for a sample from the Sokolov basin. A methanol/water mixture (1:1)
      extracted 15.1 - 38.7% of the total arsenic from Velenje basin samples but only
      2.2-7.1% from Sokolov and Trbovlje basin samples. Extracts from the Velenje basin
      samples contained mainly the tetramethylarsonium ion (0.14 - 0.92 microg g(-1))
      with considerable amounts of arsenate (0.15 - 0.85 microg g(-1)) and monomethyl
      arsonic acid 0.04 - 0.27 microg g(-1)). In methanol/water extracts from samples
      from the Sokolov and Trbovlje basins inorganic arsenic (arsenate) prevailed (0.26
      - 37.1 microg g(-1)), but at least trace amounts of organic arsenic compounds
      were found as well. It is likely that biogeochemical degradation of organic
      material is related to the unexpected organoarsenic compounds found in low-rank
      coals. However, it should also not be ruled out that abiogenic synthesis could
      have taken place in the carbon-rich environment under the harsh conditions
      present (elevated temperature and pressure).

PMID- 15952349
TI  - PCBs and selected organochlorine compounds in Italian mountain air: the influence
      of altitude and forest ecosystem type.
AB  - Passive air samplers (polyurethane foam disks) were deployed on an altitudinal
      transect in the rural Italian Alps to investigate the potential influence of
      forest cover on air concentrations. Samplers were exposed overtwo periods, each
      of several weeks, either in clearings or in forests. In the first period, there
      was high leaf coverage (high leaf area index, LAI); in the second, the LAI was
      low after the autumnal leaf fall. PCBs sequestered in the PUF generally declined
      with altitude, for example, in the clearings PCBs-28, 52, 90/101, 118, and 138,
      all showed statistically significant declines (p < 0.05). The mass of HCB
      sequestered increased with altitude, evidence of cold condensation. Ratios of the
      forest:clearing concentrations were calculated; this ratio expresses the
      filtering ability of forests to deplete air concentrations compared to the
      adjacent clearings. During the high LAI sampling period, these depletion factors
      ranged between 0.93 and 0.54 and were inversely correlated with temperature
      corrected log K0A. This relationship was notobserved during the low LAI sampling
      period. The depletion factors were normalized using the LAI to give a density
      independent depletion factor (DIDF). The slopes of the correlations with K0A were
      comparable for broadleaf or coniferous forests at different altitudes, suggesting
      that leaf surfaces determine the exchanges with air. Broadleaf forests at 1000
      and 1400 m showed similar behavior, while a conifer forest at 1800 m gave
      depletion factors which were higher by about a factor of 2. It is suggested that
      DIDF can be used in regional environmental fate models to estimate the
      contribution of forests to contaminant fate.

PMID- 15952350
TI  - Enantiomer fractions of organic chlorinated pesticides in arctic marine ice
      fauna, zooplankton, and benthos.
AB  - Stereoisomers of chiral chlorinated pesticides (alpha-HCH (HCH =
      hexachlorocyclohexane), trans- and cis-chlordane, MC5, o,p'-DDT) were quantified
      in arctic marine invertebrates (ice-associated amphipods Gammarus wilkitzkii,
      pelagic copepods Calanus hyperboreus, krill Thysanoessa inermis, and amphipods
      Themisto libellula, and benthic amphipods Paramphithoe hystrix). Enantiomer
      fractions (EFs) were calculated to investigate the influence of habitat,
      geographic area, and diet on selective bioaccumulation of the (-)- or (+)
      enantiomer. Depletion of the (+)-alpha-HCH enantionmer increased from ice fauna
      to zooplankton to benthos, corresponding to previous reports of EF variations
      with depth. Chlordanes and o,p'-DDT also showed the strongest enantioselective
      bioaccumulation in benthic amphipods and less so in zooplankton and ice fauna,
      which had closer to racemic EFs. Neither diet nor geographic area explained EF
      differences among samples. Nonracemic EFs in benthos may be related to
      stereoselective biotransformation, but is most likely reflecting vertical
      distribution of EFs in the water column and sediments, as demonstrated earlier
      for alpha-HCH in the Canadian and European Arctic.

PMID- 15952351
TI  - Loosely bound oxytetracycline in riverine sediments from two tributaries of the
      Chesapeake bay.
AB  - The fate of antibiotics that bind to riverine sediment is notwell understood. A
      solution used in geochemical extraction schemes to determine loosely bound
      species in sediments, 1 M MgCl2 (pH 8), was chosen to determine loosely bound,
      and potentially bioavailable, tetracycline antibiotics (TCs), including
      oxytetracycline (5-OH tetracycline) (OTC) in sediment samples from two rivers on
      the eastern shore of the Chesapeake Bay. Bottom sediments were collected at sites
      upstream from, at, and downstream from municipal sewage-treatment plants (STPs)
      situated on two natural waterways, Yellow Bank Stream, MD, and the Pocomoke
      River, MD. Concentrations of easily desorbed OTC ranged from 0.6 to approximately
      1.2 microg g(-1) dry wt sediment in Yellow Bank Stream and from 0.7 to
      approximately 3.3 microg g(-1) dry wt sediment in the Pocomoke River.
      Concentrations of easily desorbable OTC were generally smaller in sediment
      upstream than in sediment downstream from the STP in the Pocomoke River. STPs and
      poultry manure are both potential sources of OTC to these streams. OTC that is
      loosely bound to sediment is subject to desorption. Other researchers have found
      desorbed TCs to be biologically active compounds.

PMID- 15952352
TI  - Brominated flame retardants in sediment cores from Lakes Michigan and Erie.
AB  - The history of polybrominated diphenyl ethers (PBDEs) and the major
      polybrominated biphenyl congener (BB-153) was studied in dated sediment cores
      taken from Lakes Michigan and Erie. The surficial concentration of total PBDE (65
      [corrected] ng/g dry weight) in Lake Michigan was about 1.6 [corrected] times
      higher than that in Lake Erie (40 ng/g) and about 5 times higher than that
      [corrected] in Lake Superior (approximately 12 ng/g). The concentrations of total
      PBDEs in these sediments have increased rapidly, with doubling times of 5-10
      years, reflecting the increasing market demand for these flame retardants over
      the last 30 years. BDE-209 was found to be the predominant congener in both
      sediment cores, making up approximately 95% [corrected] of the total PBDE load.
      The inventories of total PBDEs in Lakes Michigan and Erie were both [corrected]
      40 ng/cm2 [corrected] The total burdens of these compounds in the sediment of
      Lakes Michigan and Erie were 23 [corrected] and 10 metric tons, respectively. We
      estimate [corrected] the total burden of these compounds in all of the Great
      Lakes is on the order of 100 [corrected] tons. In both lakes, BB-153 was found to
      increase rapidly during the 1970s and to peak around 1980.

PMID- 15952353
TI  - Comparative investigation of low-molecular-weight fulvic acids of different
      origin by SEC-Q-TOF-ms: new insights into structure and formation.
AB  - Size exclusion chromatography (SEC) coupled to electrospray ionization quadrupole
      time-of-flight mass spectrometry (ESI-Q-TOF-MS) was used to analyze the elemental
      composition and structure of low-molecular-weight fulvic acid molecules. It is
      shown that the set of hundreds of individual molecules form a homogeneous and
      structurally unique class of compounds that can be clearly differentiated from
      any other class of biogenic matter investigated to date. The molecular
      composition of low-molecular-weight fulvic acids in isolates of very different
      origin (surface water, groundwater, peat) is virtually indistinguishable.
      Significant and characteristic differences are, however, recognized when
      qualitative information and quantitative information provided by ESI-Q-TOF-MS are
      linked to each other. The relative frequency of the various molecules in each
      mixture can differ significantly, with the peat showing higher intensity of the
      aromatic and less carboxylated molecules of this set, whereas the aquatic fulvic
      acids show a strong contribution of the molecules with less aromaticity and a
      higher carboxylate content. The identity of fulvic acid molecules in isolates of
      different origin implies that no specific source material is required forfulvic
      acid formation but that they may be formed from different sources by different
      oxidative processes.

PMID- 15952354
TI  - Distribution of polybrominated diphenyl ethers in sediments of the Pearl River
      Delta and adjacent South China Sea.
AB  - Spatial and temporal distributions of polybrominated diphenyl ethers (PBDEs) in
      sediments of the Pearl River Delta (PRD) and adjacent South China Sea (SCS) of
      southern China were examined. A total of 66 surface sediment samples were
      collected and analyzed to determine the concentrations of 10 PBDE congeners (BDE
      28, -47, -66, -100, -99, -154, -153, -138, -183, and -209). The concentrations of
      BDE-209 and SigmaPBDEs (defined as the sum of all targeted PBDE congeners except
      for BDE-209) ranged from 0.4 to 7340 and from 0.04 to 94.7 ng/g, respectively.
      The SigmaPBDEs concentrations were mostly < 50 ng/g, within the range for
      riverine and coastal sediments around the world, whereas the BDE-209
      concentrations at the most contaminated sites were at the high end of the
      worldwide figures. Congener compositions were dominated by BDE-209 (72.6 -
      99.7%), with minor contributions from penta- and octa-BDEs. Slightly different
      PBDE compositions were observed among samples collected from different locations,
      attributable to possible decomposition of highly brominated congeners and/or
      redistribution between particles of various sizes during atmospheric or fluvial
      transportation. The PBDE patterns in the SCS and Pearl River Estuary sediments
      were similar to those in sediments of the Zhujiang and Dongjiang Rivers,
      reflecting the widespread influence from local inputs. Analyses of two short
      sediment cores collected from the Pearl River Estuary showed that concentrations
      of BDE-209 rapidly increased in the upper layers of both cores, coincident with
      the growth of the electronics manufacturing capacities in the PRD region. The
      major sources of PBDEs were probably waste discharges from the cities of
      Guangzhou, Dongguan, and Shenzhen, the three fastest growing urban centers in the
      PRD.

PMID- 15952355
TI  - Dissolved trace element concentrations in the East River-Long Island Sound
      system: relative importance of autochthonous versus allochthonous sources.
AB  - Dissolved trace metal (Ag, Cd, Cu, Fe, Ni, Pb, and Zn), inorganic nutrient (NO3,
      NH4, PO4, H4SiO4), and DOC concentrations were measured at 43 stations during low
      (July 2000) and high (April 2001) river discharge conditions in surface waters of
      Long Island Sound (LIS). To evaluate the impact of fluvial sources to the total
      metal budget of the sound, samples were collected from major tributaries
      discharging into LIS (Thames, Quinnipiac, Housatonic, Connecticut, and East
      Rivers). To compare LIS with other coastal embayments, samples were also
      collected from five LIS coastal embayments (Manhassett Bay, Huntington Harbor,
      Oyster Bay, Hempstead Harbor, and Port Jefferson Harbor), which are monitored by
      the U.S. National Status and Trends Program. Metal and nutrient distributions
      identified two biogeochemical regimes within LIS: an area of relatively high
      nutrient and metal concentrations in the East River/Narrows region in western LIS
      and an area in the eastern region of the sound that had comparatively lower
      concentrations. Mass balance estimates indicated that, during low flow
      conditions, the East River was the dominant allochthonous source of most trace
      metals (Ag, Cd, Cu, Ni, Zn) and inorganic nutrients (NO3 and PO4); during high
      flow conditions, the most influential source of these constituents was the
      Connecticut River. Mass balance estimates also evidenced a large autochthonous
      source of Cu, Ni, and Zn, as their spatial distributions displayed elevated
      concentrations away from point sources such as the East River. Principal
      component analysis suggested that metal and nutrient distributions in the LIS
      system were influenced by different seasonal processes: remobilization from
      contaminated sediments, anthropogenic inputs from sewage discharges and
      phytoplankton scavenging during the spring freshet, and benthic remobilization
      during summer conditions.

PMID- 15952356
TI  - Long-term recovery of PCB-contaminated sediments at the Lake Hartwell superfund
      site: PCB dechlorination. 1. End-member characterization.
AB  - Under anaerobic conditions, such as those typically found in buried sediments,
      the primary metabolic pathway for polychlorinated biphenyls (PCBs) is reductive
      dechlorination in which chlorine removal and substitution with hydrogen by
      bacteria result in a reduced organic compound with fewer chlorines. Vertical
      sediment cores were collected from Lake Hartwell (Pickens County, SC) and
      analyzed in 5-cm intervals for 107 PCB congeners in a total of more than 280
      samples from 18 sediment cores and surface samples. This paper reports on
      extensive PCB dechlorination measured in Lake Hartwell sediments and the
      characterization of dechlorination end-member (EM) patterns using chemical
      forensic methods. PCB congener fingerprinting and a multivariate receptor
      modeling method, polytopic vector analysis (PVA), were used for identification
      and characterization of weathered and dechlorinated PCB congener patterns.
      Dechlorination resulted in a substantial shift in buried sediments from tetra-
      through decachlorobiphenyl congeners to mono- through trichlorobiphenyl
      congeners. Mono- through trichlorobiphenyls comprised approximately 80% of the
      PCBs in buried sediments that underwent maximum dechlorination as compared to
      approximately 20% in surface sediments. The major concentration decreases were
      seen in the tetra- through hexachlorobiphenyl homologues, which accounted for
      over 90% of the dechlorination. Octa- through decachlorobiphenyl congeners also
      were dechlorinated, but their overall contribution to dechlorination was
      relatively small due to their low initial concentrations (< 5%). The net
      accumulation of 2-CB, 2,2'/2,6-DCBs, 2,4'-DCB, 2,2',4-TCB, and 2,2',6-TCB at Lake
      Hartwell matched characteristic PCB dechlorination products reported in the
      literature, such as those for Processes M, Q, and C; and the persistence of
      tetrachlorobiphenyls (TeCBs) that contained 24- and 25-congener groups resembled
      dechlorination Processes H or H'. Although dechlorination tended to be very
      extensive in most of the cores, it was not always consistent from core to core or
      at various depth intervals within a single core. The reason for this variability
      in dechlorination extent could not be determined from the existing data and did
      not appear to correlate with such factors as PCB concentration, total organic
      carbon, or age. The authors used fingerprinting analysis and a PVA multivariate
      receptor model as exploratory data analysis tools to characterize PCB sources and
      their alteration patterns. Dominant sources and alteration patterns were
      determined in this large data set by comparing PVA EM patterns with known source
      patterns (i.e., Aroclors or Aroclor mixtures) and literature-reported alteration
      patterns. PVA also afforded an opportunity to characterize the vertical and
      lateral distributions of the weathered and unweathered PCB source patterns and
      dechlorination patterns, a task that would have been much more difficult to
      accomplish through comparison of chromatograms alone.

PMID- 15952357
TI  - Long-term recovery of PCB-contaminated sediments at the Lake Hartwell superfund
      site: PCB dechlorination. 2. Rates and extent.
AB  - This paper reports on extensive polychlorinated biphenyl (PCB) dechlorination
      measured in Lake Hartwell (Pickens County, SC) sediments. Vertical sediment cores
      were collected from 18 locations in Lake Hartwell (Pickens County, SC) and
      analyzed in 5-cm increments for PCB congeners. The preferential loss of meta and
      para chlorines with sediment depth demonstrated that PCBs in the sediments
      underwent reductive dechlorination after burial. Notably, ortho chlorines were
      highly conserved for more than 5 decades; since the first appearance of PCBs, ca.
      1950-1955. These dechlorination characteristics resulted in the accumulation of
      lower chlorinated congeners dominated by ortho chlorine substituents.
      Dechlorination rates were determined by plotting the numbers of meta plus para
      chlorines per biphenyl molecule (mol of chlorine/mol of PCB) with sediment age.
      Regression analyses showed linear correlations between meta plus para chlorine
      concentrations with time. The average dechlorination rate was 0.094 +/- 0.063 mol
      of Cl/mol of PCB/yr. The rates measured using the 2001 cores were approximately
      twice those measured using the 2000 cores, most likely because the 2001 cores
      were collected only at transects O, L, and I, which had the highest rates
      measured in 2000. An inverse of the dechlorination rates indicated that 16.4 +/-
      11.6 yr was required per meta plus para chlorine removal (ranging from 4.3 to
      43.5 yr per chlorine removal). The rates determined from this study were 1-2
      orders of magnitude lower than rates reported from laboratory microcosm studies
      using Hudson River and St. Lawrence River sediments, suggesting that
      dechlorination rates reported for laboratory experiments are much higher than
      those occurring in situ.

PMID- 15952358
TI  - Traffic as a source of organophosphorus flame retardants and plasticizers in
      snow.
AB  - Snow samples collected in northern Sweden at a road intersection and an airport
      indicated that traffic is a source of organophosphorus flame retardants and
      plasticizers (OPs) in the outdoor environment. Analysis of snow samples taken at
      distances of 2, 100, and 250 m from the road intersection showed that the total
      amount of OPs declined as distance increased. Of the 11 analyzed substances, tris
      (2-chloroisopropyl) phosphate (TCPP) dominated in the snow samples from the
      intersection, with levels of 170, 130, and 110 ng/kg snow at distances of 2, 100,
      and 250 m. Similar amounts of TCPP were found at the airport (100-220 ng/kg).
      These levels are approximately twice as high as the level found in the reference
      snow sample from a remote area (70 ng/kg). A possible explanation for the higher
      levels of TCPP found close to the road intersection is that it may be emitted
      from the interior of cars via their ventilation systems. Triphenyl phosphate
      (TPP) was identified in lubricants and in waste oil from vehicles, and thus,
      leakage of transmission and motor oils is a probable source of TPP found at the
      sampled sites. Ten OPs were detected in the three samples from the airport, of
      which tributyl phosphate (TBP) was the most abundant, at levels 3 orders of
      magnitude higher than in the reference sample, that is, 25 000 compared to 19
      ng/kg. The main source of TBP at the airport was traced to aircraft hydraulic
      fluid. Analysis of background air and deposition samples indicated that some OPs
      are subject to long-range air transportation.

PMID- 15952359
TI  - Tracking sources of unsaturated zone and groundwater nitrate contamination using
      nitrogen and oxygen stable isotopes at the Hanford site, Washington.
AB  - The nitrogen and oxygen isotopic compositions of nitrate in pore water extracts
      from unsaturated zone (UZ) core samples and groundwater samples indicate at least
      four potential sources of nitrate in groundwaters at the U.S. DOE Hanford Site in
      south-central Washington. Natural sources of nitrate identified include
      microbially produced nitrate from the soil column (delta15N of 4 - 8 per
      thousand, delta18O of -9 to 2 per thousand) and nitrate in buried caliche layers
      (delta15N of 0-8 per thousand, delta 18O of -6to 42 per thousand). Isotopically
      distinctindustrial sources of nitrate include nitric acid in low-level disposal
      waters (delta15N approximately per thousand, delta 18O approximately 23%o) per
      thousandnd co-contaminant nitrate in high-level radioactive waste from plutonium
      processing (6'5delta1of 8-33 % o, per thousand18delta oO -9 to 7%0). per
      thousandThe isotopic compositions of nitrate from 97 groundwater wells with
      concentrations up to 1290 mg/L NO3- have been analyzed. Stable isotope analyses
      from this study site, which has natural and industrial nitrate sources, provide a
      tool to distinguish nitrate sources in an unconfined aquiferwhere concentrations
      alone do not. These data indicate that the most common sources of high nitrate
      concentrations in groundwater at Hanford are nitric acid and natural nitrate
      flushed out of the UZ during disposal of low-level wastewater. Nitrate associated
      with high-level radioactive UZ contamination does not appear to be a major source
      of groundwater nitrate at this time.

PMID- 15952360
TI  - Arsenate adsorption structures on aluminum oxide and phyllosilicate mineral
      surfaces in smelter-impacted soils.
AB  - A clearer understanding of arsenic (As) retention and transport in forest soils
      impacted by copper smelter emissions may reduce risks to human health and provide
      insight into As behavior in the vadose zone. On Vashon-Maury Island in Puget
      Sound, As is predominantly associated with the fine (< 63 microm) fraction of
      surficial soils. X-ray diffraction of oriented samples from the < 2 microm size
      fraction indicate that clinochlore isthe dominant phyllosilicate. X-ray
      absorption spectroscopy (XAS) was employed to examine As oxidation state and
      local coordination environment in impacted soil samples. Arsenic is present as
      As(V) in tetrahedral coordination with oxygen, associated with aluminum (Al)
      octahedra in bidentate binuclear (bridging) structures with As-Al distances of
      3.15 - 3.16 angstroms. Including multiple scattering (MS) paths derived from the
      arsenate tetrahedron in esperanzaite significantly improved the match between XAS
      fine structure (EXAFS) data and models generated from theoretical phase and
      amplitude functions. The data are interpreted to indicate arsenate adsorption
      onto poorly crystalline aluminum oxyhydroxides and/or the edges of clinochlore
      interlayer hydroxyl sheets with constrained geometries causing MS to be important
      This implies that As initially released from the smelter as particulate As(III)
      and As(V) oxides was oxidized, dissolved, and adsorbed onto soil minerals and
      colloids; no evidence for relic arsenic oxide was observed. Physical transport of
      arsenic oxide particles and As adsorbed on soil colloids may account for limited
      downward migration of As within the soil column. The oxidizing and mildly acidic
      pH conditions in the upper vadose zone promote stable sorption complexes; barring
      substantial changes in soil chemistry, As is not expected to experience
      significant mobilization.

PMID- 15952361
TI  - Maternal diet during oogenesis is the major source of methylmercury in fish
      embryos.
AB  - Development of the early life stages of fishes can be affected adversely by
      methylmercury (MeHg) transferred from the maternal parent to the developing egg.
      We examined maternal transfer of MeHg to eggs of fathead minnows Pimephales
      promelas and evaluated the role of maternal MeHg burden versus that in the
      maternal dietduring oogenesis on egg concentrations. Juvenile fish were fed one
      of four diets until sexual maturity (phase 1): A control diet (0.06 microg of Hg
      g(-1) dry weight) and three that were contaminated with MeHg at 0.88 (low), 4.11
      (medium), and 8.46 microg of Hg g(-1) (high). At sexual maturity, female fish
      were paired with a male, again fed one of the four diets, and allowed to
      reproduce (phase 2). To assess the significance of female dietary exposure during
      oogenesis on MeHg in eggs, some fish were fed diets during phase 2 that differed
      from those during phase 1. Mean concentrations and burdens of MeHg in eggs from
      fish fed the same diet throughout the experiment varied with MeHg content of the
      maternal diet and were related positively to levels in the carcass of the
      maternal fish. However, MeHg in eggs was not proportional to that in carcasses
      among dietary treatments; MeHg in eggs from adults fed the control, low, medium,
      and high MeHg diets averaged 14%, 25%, 32%, and 35% of that in adults. For fish
      fed the control diet as juveniles and MeHg-contaminated diets after reaching
      sexual maturity, MeHg in eggs increased rapidly with duration of maternal dietary
      exposure prior to spawning. Moreover, concentrations of MeHg in eggs from fish
      fed the same contaminated diet as both juveniles and sexually mature adults were
      not related to the duration of adult exposure, and they were not appreciably
      greater than those from fish fed contaminated diets only just priorto spawning.
      These results indicate that the diet of the maternal adult during oogenesis, and
      not adult body burden, is the principal source of MeHg in fish eggs. Accordingly,
      the exposure of embryonic wild fishes to MeHg depends on levels of the
      contaminant in prey of the adult during oogenesis, which can vary intra- and
      interannually.

PMID- 15952362
TI  - Effects of mercury on neurochemical receptors in wild river otters (Lontra
      canadensis).
AB  - Fish-eating wildlife, such as river otters (Lontra canadensis), accumulate
      mercury (Hg) at concentrations known to impair animal behavior, but few studies
      have explored the underlying biochemical changes that precede clinical
      neurotoxicity. The objective of this study was to determine if Hg exposure can be
      related to concentrations of neurochemical receptors in river otters. River otter
      carcasses (n = 66) were collected in Ontario and Nova Scotia (Canada) by local
      trappers in 2002-2004. Concentrations of Hg (total and organic) were measured in
      the cerebral cortex and cerebellum. Saturation binding curves for the cholinergic
      muscarinic acetylcholine (mACh) receptor and dopamine-2 (D2) receptor were
      completed for each animal to calculate receptor density (Bmax) and ligand
      affinity (Kd). Negative correlations were found between concentrations of Hg and
      mACh receptor Bmax (r(total) Hg = -0.458, r(inorganic) Hg = -0.454, r(organic) Hg
      = -0.443) in the cerebral cortex. A negative correlation was also found between
      concentrations of total Hg and D2 receptor Bmax (r = -0.292) in the cerebral
      cortex. These results suggest that neurochemical receptors may prove useful as
      novel biomarkers of Hg exposure and neurotoxic effects in wildlife. Given the
      importance of cholinergic and dopaminergic systems in animal physiology, the
      ecological implications of these changes need to be investigated.

PMID- 15952363
TI  - Interaction forces between colloids and protein-coated surfaces measured using an
      atomic force microscope.
AB  - Bacterial surfaces contain proteins, polysaccharides, and other biopolymers that
      can affect their adhesion to another surface. To better understand the role of
      proteins in bacterial adhesion, the interactions between two different model
      colloids (glass beads and carboxylated latex microspheres) and four proteins
      covalently bonded to glass surfaces were examined using colloid probes and an
      atomic force microscope (AFM). Adhesion forces between an uncoated glass colloid
      probe and protein-coated surfaces, measured in retraction force curves, decreased
      in the order poly-D-lysine > lysozyme > protein A > BSA. This ordering was
      consistent with the relative calculated charges of the proteins at neutral pH and
      the zeta-potentials measured for glass beads and latex microspheres coated with
      these proteins. When the glass bead was coated with a protein (BSA), overall
      adhesion forces between the protein-coated colloid and the protein-coated
      surfaces were reduced, and the adhesion force for each protein decreased in the
      same order observed in experiments with the uncoated glass bead. When latex
      colloid probes were coated with BSA, adhesion forces were significantly larger
      than those measured with BSA-coated glass colloid probes under the same
      conditions, demonstrating that the nature of the underlying colloid can affect
      the measured interaction forces. In addition, the adhesion forces measured with
      the BSA-coated latex colloid increased in a different order (BSA < lysozyme <
      protein A < poly-D-lysine) than that observed using the BSA-coated glass colloid.
      It was also found that increasing the solution ionic strength consistently
      decreased adhesion forces. This result is contrary to the general observation
      that bacterial adhesion increases with ionic strength. It was speculated that
      conformational changes of the protein produced this decrease in adhesion with
      increased ionic strength. These results suggest the need to measure nanoscale
      adhesion forces in order to understand better molecular scale interactions
      between colloids and surfaces.

PMID- 15952364
TI  - Effect of airflow setting on the organic composition of woodheater emissions.
AB  - Fine particle emissions from woodheaters are large contributors to ambient
      atmospheric pollution in a number of regional centers in Australia. The health
      impact of woodsmoke is not limited to the particle loading alone, and a wide
      range of toxic inorganic and organic compounds are also emitted as gases or
      adsorbed onto particles. The organic composition of woodsmoke was determined from
      two heater models operated using different airflow settings. Particle emission
      factors varied between 3 and 36 g per kg dry wood burned, with higher burn rates
      (open airflow) producing significantly less particle mass per kg wood burned than
      the low burn rates (closed airflow). Over 90 organic compounds were quantified
      from the vapor- and particle-phases, including furans, methoxyphenols, and other
      substituted aromatics, PAHs, maltols, and the sugar levoglucosan. Emission
      factors for the majority of the particle-phase compounds increased as the airflow
      was progressively closed, but decreased for some PAHs and other compounds found
      predominantly in the vapor-phase. Levoglucosan was the single most abundant
      compound, contributing 5-16% of the total particle mass. Although there was some
      variation in levoglucosan emissions between heater models, the fact that
      levoglucosan emissions vary relatively little between airflow conditions for a
      given heater provides the potential to use it as a general tracer for woodsmoke.
      In contrast, the mass fractions of many other particle-phase compounds were
      considerably higher when operated with a closed airflow.

PMID- 15952365
TI  - Hepatic CYP1A induction by dioxin-like compounds, and congener-specific
      metabolism and sequestration in wild common cormorants from Lake Biwa, Japan.
AB  - The present study examines the effects of polychlorinated dibenzo-p-dioxins
      (PCDDs), polychlorinated dibenzofurans (PCDFs), and coplanar polychlorinated
      biphenyls (Co-PCBs) on hepatic cytochromes P450 (CYP) in the wild population of
      common cormorants from Lake Biwa, Japan, and discusses functional roles of CYP1A
      in terms of correlation analysis between tissue concentrations of individual
      congeners and expression levels of CYP1A. Levels of alkoxyresorufin (methoxy-,
      ethoxy-, pentoxy-, and benzyloxyresorufin) O-dealkylase activities and a protein
      cross-reacted with anti-rat CYP1A1 polyclonal antibodies showed significant
      positive correlations with total 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic
      equivalents (TEQs) or TEQs for most individual congeners in the liver of
      cormorants, suggesting induction of CYP1A-like protein by these chemicals. In
      contrast, TEQs for lower chlorinated congeners, 2,3,7,8-T4CDF and PCB77, showed
      relatively low correlations with the expression level of CYP1A-like protein.
      Concentrations of 2,3,7,8-T4CDF and PCB77 normalized to a relatively recalcitrant
      congener, PCB169, were negatively correlated with the CYP1A-like protein level.
      These results indicate preferential metabolism of those congeners by CYP1A-like
      protein that was induced by TEQs. Concentration ratios of liverto pectoral muscle
      for certain congeners significantly increased with an elevation of the CYP1A-like
      protein level. Comparing the results in the present study with those of previous
      studies using rodents treated with certain dioxin-like congeners, these congeners
      in the liver may be sequestered by CYP1A. Levels of cross-reactive proteins with
      anti-rat CYP2B1, CYP2C6, and CYP3A2 polyclonal antibodies correlated with neither
      TEQs nor liver/muscle concentration ratios of congeners. We conclude that the
      potential for CYP1A induction, and metabolism and sequestration of dioxin-like
      compounds by CYP1A, may be a critical factor for assessing the ecological risk in
      wild avian species.

PMID- 15952366
TI  - Spatial distributions of Cryptosporidium oocysts in porous media: evidence for
      dual mode deposition.
AB  - Spatial distributions of Cryptosporidium parvum oocysts in columns packed with
      uniform glass-bead collectors were measured over a broad range of physicochemical
      conditions. Oocyst deposition behavior is shown to deviate from predictions based
      on classical colloid filtration theory (CFT) in the presence of repulsive
      (unfavorable) colloidal interactions. Specifically, CFT tends to predict greater
      removal of oocysts (less transport) than that observed in controlled laboratory
      experiments. Comparison of oocyst retention with results obtained using
      polystyrene latex particles of similar size suggests that mechanisms controlling
      particle deposition are the same in both systems. At a given ionic strength, the
      deposition of Cryptosporidium oocysts is generally greater than that of the
      microspheres; however, this discrepancy is partly attributable to large
      differences in oocyst and microsphere zeta potentials. A dual deposition mode
      (DDM) model is applied which considers the combined influence of "fast" and
      "slow" oocyst deposition due to the concurrent existence of favorable and
      unfavorable oocyst-collector interactions. Model simulations of retained oocyst
      profiles and suspended oocyst concentration at the column effluent are consistent
      with experimental data. Because classic CFT does not account for the effect of
      dual mode deposition (i.e., simultaneous "fast" and "slow" oocyst deposition),
      these observations have important implications for predictions of oocyst
      transport in subsurface environments, where repulsive electrostatic interactions
      predominate. Supporting elution experiments further suggest that specific surface
      interactions between oocyst wall macromolecules and the glass bead collectors
      could retard or even completely inhibit oocyst release upon perturbation in
      solution chemistry.

PMID- 15952367
TI  - Triplet-sensitized photodegradation of sulfa drugs containing six-membered
      heterocyclic groups: identification of an SO2 extrusion photoproduct.
AB  - The aquatic photochemical behavior of a class of sulfa drugs containing six
      membered heterocyclic substituents (sulfamethazine, sulfamerazine, sulfadiazine,
      sulfachloropyridazine, and sulfadimethoxine) was investigated. Photodegradation
      of the sulfa drugs in a natural water sample was significantly enhanced relative
      to the degradation in deionized water, with the exception of sulfadimethoxine.
      This indicated an indirect photochemical process that was identified through the
      use of quenchers to be attributable to interaction with triplet excited-state
      dissolved organic matter (3DOM). The direct photolysis rate constant and quantum
      yield for both the neutral and anionic species of each sulfa drug were calculated
      using matrix deconvolution methods. The quantum yield values range from 0.01 x
      10(-3) for the neutral form of sulfadimethoxine to 5 x 10(-3) for the anionic
      form of sulfamethazine and are significantly lower than those observed in a
      previous study for sulfa drugs containing five-membered heterocyclic
      substituents, although the rate constants are of similar magnitude. The primary
      product formed in both direct and indirect photodegradation for all five
      compounds was identified as a sulfur dioxide extrusion product. The predicted
      environmental half-lives solely attributable to direct photolysis range from 8.6
      h in midsummer at 30 degrees latitude in pH 7 surface water for
      sulfachloropyridazine to 420 h in midwinter at 45 degrees in pH 7 surface water
      for sulfadimethoxine. These half-lives, except for sulfadimethoxine, will be
      decreased by interaction with 3DOM.

PMID- 15952368
TI  - Persistence and biodegradation of monoethanolamine and 2-propanolamine at an
      abandoned industrial site.
AB  - Soil and groundwater samples were collected at the site of a former chemical
      processing plant in areas impacted by accidental releases of MEA
      (monoethanolamine) and IPA (2-propanolamine or isopropanolamine). Although their
      use had ceased ca. 10 years before sample collection, soils collected at
      contamination sites had MEA concentrations ranging from ca. 400 to 3000 mg/kg and
      IPA concentrations from ca. 30 to 120 mg/kg. Even though alkanolamines are
      miscible in water, transport to groundwater was slow, apparently because they are
      present in soil as bound cations. Only one groundwater sample (near the most
      highly contaminated soil)from wells directly adjacentto and down-gradient from
      the contaminated soils had detectable MEA, and none had detectable IPA. However,
      ammonia was found in the soil samples collected in the MEA-contaminated areas
      (ca. 500-1400 mg/kg) and the groundwater (80-120 mg/L), as would be consistent
      with bacterial degradation of MEA to ammonia, followed by transport of ammonia
      into the groundwater. Counts for bacteria capable of using MEA or IPA as a sole
      carbon source were ca. 5 x 106 and 1 x 106 (respectively) per gram in
      uncontaminated site soil, but no such organisms were found in highly contaminated
      soils. Similarly, bacterial degradation of MEA in slurries of highly contaminated
      soils was slow, with ca. 8-20 days required for half of the initial
      concentrations of MEA to be degraded at 20 degrees C and 30-60 days at 10 degrees
      C. In contrast, bacterial degradation studies using uncontaminated site soils
      spiked with ca. 1300 mg/L either MEA or IPA showed very rapid degradation of both
      compounds,with more than 99% degradation occurring in less than 3 days with
      quantitative conversion to ammonia, followed by slower conversion to nitrite and
      nitrate. The results obtained in the site soils, the groundwater samples, and
      from the biodegradation studies demonstrate that MEA and IPA can persist for
      decades on soil at high (hundreds of mg/kg) concentrations without significant
      migration into groundwater, despite the fact that they are miscible in water.
      Since MEA and IPA exist primarily as cations at the pH of site soils, their
      persistence apparently results from strong binding to soil, as well as inhibition
      of natural bioremediation in highly contaminated field soils.

PMID- 15952369
TI  - Photochemical production of ionic and particulate aluminum and iron in lakes.
AB  - Photochemical liberation of allochthonous organically bound aluminum (Al) and
      iron (Fe) and in-lake hydroxide precipitation are important sources of these
      metals to lake sediments. Mass budgets of ionic Al and Fe (Ali, Fei), organically
      bound Al and Fe (Alo, Feo), and particulate Al and Fe (Alp, Fep) were measured
      for two western Czech Republic forest lakes (Plesne and Certovo) in the 2000-2003
      hydrological years. The lakes were net sinks of Ali, Alo, and Feo and net sources
      of Alp and Fep. The average Alo and Feo inputs from terrestrial sources (66-110
      and 12-17 mmol m(-2) yr(-1), respectively, on a lake area basis) were reduced 45%
      and 25% in the lakes. Mass budgets of dissolved organic carbon, particulate
      organic C, and Al species indicated that only a minor part of the observed in
      lake retention of Alo could be explained by coagulation and sedimentation of
      organic matter, or from Ali hydrolysis and formation of Alp. Laboratory
      experiments with a short-time irradiation (approximately 300 nm, approximately
      800 W m(-2)) of water from inlets to Plesne Lake showed the importance of
      photochemical processes in the liberation of Al and Fe from Alo and Feo. After 12
      h of irradiation, Alo and Feo concentrations decreased 54 +/- 6% and 70 +/- 16%,
      respectively, compared to those of the dark controls. The photoliberated Alo and
      Feo increased the Ali and Fei concentrations reciprocally, on a 1:1 mass basis.
      The subsequent hydrolysis of Ali and Fe1 in lakes forms insoluble hydroxides,
      increasing the sediment concentrations of Al and Fe.

PMID- 15952370
TI  - Long-term fate of polychlorinated biphenyls and polycyclic aromatic hydrocarbons
      in an agricultural soil.
AB  - Laboratory studies are useful for understanding the behavior of persistent
      organic pollutants (POPs) in soil, although such investigations do not always
      relate directly to field conditions. Outdoor lysimeter studies may be used to
      overcome this problem. This work aimed to investigate the behavior of two
      polycyclic aromatic hydrocarbons (PAHs) (fluoranthene and benzo[a]pyrene) and two
      polychlorinated biphenyls (PCBs; congeners 28 and 52) in soil, using lysimeters
      established in 1990 atthe Agrosphere Institute (Forschungszentrum Julich GmbH,
      Germany). The two PAHs were in one lysimeter, and the PCBs were in a second
      lysimeter. Afurther aim of the study was to determine soil half-lives for each of
      the contaminants. The overall decline in PAH concentrations was considerably
      greater than forthe PCBs over the 152 month study. The PCBs exhibited greater
      chemical extractability than the PAHs and were demonstrated to have migrated
      through the soil column to a greater extent than the PAHs. Loss of PCBs from
      surface soil was not considered to have been congener specific for the two PCB
      congeners in this study. The two PAHs varied in their extents of total loss and
      movement through the soil column. Soil half-lives were determined as 10.9 y for
      [12C]PCB 28, 11.2 yr for [12C]PCB 52, 2.7 yr for benzoqpyrene, and 32 d (phase 1)
      to 38 yr (phase 2) for fluoranthene. These are shown to disagree with some
      previous estimates of POP half-lives in soil, suggesting that previous studies
      underestimated persistence by 10-fold or more.

PMID- 15952371
TI  - Elevated microbial tolerance to metals and antibiotics in metal-contaminated
      industrial environments.
AB  - To test the hypothesis that industrial metal contaminants select for
      microorganisms tolerant to unrelated agents, such as antibiotics, we analyzed
      metal and antibiotic tolerance patterns in microbial communities in the intake
      and discharge of ash settling basins (ASBs) of three coal-fired power plants.
      High-throughput flow-cytometric analyses using cell viability probes were
      employed to determine tolerances of entire bacterioplankton communities, avoiding
      bias toward culturable versus nonculturable bacteria. We found that
      bacterioplankton collected in ASB discharges were significantly more tolerant to
      metal and antibiotic exposures than bacterioplankton collected in ASB intakes.
      Optical properties of microorganisms collected in ASB discharges indicated no
      defensive physiological adaptations such as formation of resting stages or
      excessive production of exopolymers. Thus, it is likely that the elevated
      frequency of metal and antibiotic tolerances in bacterioplankton in ASB
      discharges were caused by shifts in microbial community composition, resulting
      from the selective pressure imposed by elevated metal concentrations or organic
      toxicants present in ASBs.

PMID- 15952372
TI  - Spatial variation in deposition rate coefficients of an adhesion-deficient
      bacterial strain in quartz sand.
AB  - The transport of bacterial strain DA001 was examined in packed quartz sand under
      a variety of environmentally relevant ionic strength and flow conditions. Under
      all conditions, the retained bacterial concentrations decreased with distance
      from the column inlet at a rate that was faster than loglinear, indicating that
      the deposition rate coefficient decreased with increasing transport distance. The
      hyperexponential retained profile contrasted againstthe nonmonotonic retained
      profiles that had been previously observed for this same bacterial strain in
      glass bead porous media, demonstrating that the form of deviation from log-linear
      behavior is highly sensitive to system conditions. The deposition rate constants
      in quartz sand were orders of magnitude below those expected from filtration
      theory, even in the absence of electrostatic energy barriers. The degree of
      hyperexponential deviation of the retained profiles from loglinear behavior did
      not decrease with increasing ionic strength in quartz sand. These observations
      demonstrate thatthe observed low adhesion and deviation from log-linear behavior
      was not driven by electrostatic repulsion. Measurements of the interaction forces
      between DA001 cells and the silicon nitride tip of an atomic force microscope
      (AFM) showed that the bacterium possesses surface polymers with an average
      equilibrium length of 59.8 nm. AFM adhesion force measurements revealed low
      adhesion affinities between silicon nitride and DA001 polymers with approximately
      95% of adhesion forces having magnitudes < 0.8 nN. Steric repulsion due to
      surface polymers was apparently responsible for the low adhesion to silicon
      nitride, indicating that steric interactions from extracellular polymers
      controlled DA001 adhesion deficiency and deviation from log-linear behavior on
      quartz sand.

PMID- 15952373
TI  - Sorption to black carbon of organic compounds with varying polarity and
      planarity.
AB  - It is becoming increasingly clear that the products of incomplete combustion
      (soot and charcoal, collectively termed black carbon or BC) can be responsible
      for as much as 80 - 90% of the total sorption to sediments of aromatic, planar,
      and hydrophobic compounds such as polycyclic aromatic hydrocarbons or planar
      polychlorinated biphenyls. In the present study, it was investigated whether a
      nonpolar aliphatic compound (hexachloroethane) and three nonplanar bipolar
      compounds with different functional groups [free electron pairs but no aromatic
      ring (butylate) or free electron pairs and an aromatic ring (diuron, atrazine)]
      would also show strong and nonlinear sorption to a BC-enriched sediment. At a
      concentration of 1 ng/L, the extent of elevated BC sorption compared to total
      organic carbon (TOC) sorption increased in the order atrazine < hexachloroethane
      < butylate < diuron. Rationalization of the differences between the sorbates was
      attempted in terms of dispersive and steric effects. This study shows that the
      effects of strong BC sorption apply to a broader range of organic contaminants
      than previously thought, and the results will aid in a better understanding of BC
      sorption mechanisms and improved fate modeling of contaminants in the
      environment.

PMID- 15952374
TI  - Direct observation of organic contaminant uptake, storage, and metabolism within
      plant roots.
AB  - Two-photon excitation microscopy (TPEM) is used to visualize and track the uptake
      and movement of anthracene and phenanthrene from a contaminated growth medium
      into living unmodified roots of maize and wheat over a 56-day period. The
      degradation of anthracene was also directly observed within the cortex cells of
      both species. The power of this technique is that neither the plant nor the
      compound require altering (staining or sectioning) to visualize them, meaning
      they are in their natural form throughout the experiment. Initially both
      compounds bound to the epidermis along the zone of elongation, passing through
      the epidermal cells to reach the cortex within the root hair, and branching zones
      of the root. The PAHs entered the epidermis radially; however, once within the
      cortex cells this movement was dominated by slow lateral movement of both
      compounds toward the shoot. Highly focused "streams" of compound were observed to
      form over time; zones where phenanthrene concentrated extended up to 1500 microm
      in length over a 56-day period, for example, passing through several adjoining
      cells, and were detectable in cell walls and cell vacuoles. Radial movement was
      not observed to extend beyond the cortex cells to reach the vascular tissues of
      the plant. The longitudinal movement of both compounds was not observed to extend
      beyond the root base into the stem or vegetative parts of the plant. The lateral
      movement of both compounds within the cortex cells was dominated by movement
      within the cell walls, suggesting apoplastic flow through multiple cell walls,
      but with a low level of symplastic movement to transport compound into the
      cellular vacuoles. Degradation of anthracene to the partial breakdown products
      anthrone, anthraquinone, and hydroxyanthraquinone was observed directly in the
      zones of root elongation and branching. The technique and observations have
      important applications to the fields of agrochemistry and phytoremediation.

PMID- 15952375
TI  - Estrogenic activity of impurities in industrial grade bisphenol A.
AB  - The estrogenicities of 10 compounds found as impurities in industrial grade
      bisphenol A (BPA) were measured by yeasttwo-hybrid assays incorporating the human
      estrogen receptor alpha(hERalpha) orthe medaka fish (Oryziaslatipes) estrogen
      receptor alpha (medERalpha). Five impurities showed greater activity than BPA
      itself in an agonist assay for hERalpha. p-Cumylphenol, the most active of the
      impurities in the hERalpha assay, was 12 times as active as BPA. The REC10 (10%
      relative effective concentration: 10% of the activity of 10(-8)M 17,B-estradiol)
      was 710 nM. Five impurities showed greater activity than BPA in an agonist assay
      for medERa: 4,4'-(1,3-dimethylbutylidene) bisphenol and 2-(4'-hydroxy-phenyl)
      2,4,4-trimethylchroman were nearly equipotent and 9 times as active as BPA, and
      the REC10 values of these compounds in the medERalpha assay were 280 and 320 nM,
      respectively. Comparison of the experimentally determined estrogenicities of
      mixtures of BPA and 4,4'-(1,3-dimeth-ylbutylidene) bisphenol and those calculated
      by the concentrations addition (CA) method confirmed the suitability of the
      method for the prediction of the estrogenicities of the mixtures of BPA and its
      phenolic analogues. The measured estrogenicities of four samples of industrial
      grade BPA and laboratory grade (pure) BPA were not significantly different in
      either the hERalpha assay or the medERalpha assay (p > 0.05 in each case). We
      conclude that the impurities in industrial grade BPA, although some are of much
      higher estrogenic activity than BPA itself, do not significantly increase the
      estrogenicity of the industrial compound and therefore do not increase possible
      adverse health effects from such activity.

PMID- 15952376
TI  - Use of superoxide as an electron shuttle for iron acquisition by the marine
      cyanobacterium Lyngbya majuscula.
AB  - Reduction of iron from the ferric state to the ferrous state is one strategy
      employed by microorganisms in nearneutral environments to increase its biological
      availability. In recent years, the existence of mobile reducing agents produced
      bymicroorganismsto promote iron reduction, known as electron shuttles, has been
      demonstrated. Production of electron shuttles has been shown for several
      organisms, employing a variety of mostly organic molecules as the electron
      carrier. Here we show that the coastal cyanobacterium Lyngbya majuscula produces
      iron-reducing superoxide radicals (02*-) and that this facilitates increased iron
      uptake. We suggest that superoxide is a useful electron shuttle because it reacts
      rapidly and almost indiscriminately with Fe(lll)-organic complexes and its
      precursor, dissolved oxygen, is ubiquitous in the photic zone. We further suggest
      that, for these reasons, the generation of superoxide by marine oxygenic
      photosynthetic microorganisms and its use in facilitating iron uptake may be a
      reasonably widespread process.

PMID- 15952377
TI  - In-stream nitrogen attenuation: model-aggregation effects and implications for
      coastal nitrogen impacts.
AB  - Eutrophication problems in coastal and marine waters worldwide emphasize the
      significance, for the scientific community as well as the whole society, of
      relevant quantification of catchment-scale nitrogen transport from land to coast.
      Different catchment-scale nitrogen budget models use, and base management
      recommendations on, quite different process representations of and spatial
      resolution approaches to in-stream nitrogen attenuation. We compare three
      different spatial resolution approaches to modeling nitrogen loss rates in
      streams of the same drainage basin. Results show that commonly used spatial model
      aggregation may lead to artificial decrease of calibrated nitrogen loss rates
      with increasing stream depth (or flow), in addition to any such dependences that
      may prevail in independently measurable reality. Coastal nitrogen impact
      predictions and practical management implications of large-scale model
      aggregation of nitrogen attenuation rates may further differ considerably from
      those based on rates from finer resolution modeling or independent measurements.

PMID- 15952378
TI  - Computer model for municipal solid waste treatment in developing countries.
AB  - Many integrated solid waste management (ISWM) models are available but are of
      little use to developing countries such as India since they do not take into
      account typical developing countries municipal solid waste characteristics such
      as high organic content, poor performance of formal sector control and support,
      high activity of scavengers and waste pickers, etc. The goal of this study is to
      create a computer program to determine the least cost treatment and disposal
      system for a given solid waste management problem. To demonstrate its
      applicability, the model was applied to the Indian city Amritsar. A typical
      Indian city like Amritsar generates about 500 ton of MSW/d with 45% moisture
      content, 30% volatile matter, and calorific value of 1500 kcal/kg. The computer
      model was run for various technologies. Results showthatfor Amritsar city
      incineration an expenditure of U.S. dollars (USD) 6.62 is incurred, whereas
      landfilling, composting, and biomethanation digester give an income of USD 0.13,
      USD 0.20, and USD 0.23 per ton of MSW, respectively. This empirical exercise not
      only reveals the model's strengths such as highlighting important
      interdependencies in the waste management sector but also its requirement for
      quality data.

PMID- 15952379
TI  - Solid phase dosing and sampling technique to determine partition coefficients of
      hydrophobic chemicals in complex matrixes.
AB  - Determination of polymer-water and dissolved organic carbon (DOC)-water
      distribution coefficients of very hydrophobic chemicals (log K0w > 6) is not
      straightforward. Poor water solubility of the test compounds complicates the
      spiking and analysis of actual freely dissolved concentrations. By dosing a
      system via a PDMS-fiber and monitoring the depletion in the polymer, spiking and
      analysis of concentrations in the aqueous phase are avoided, and sorption to the
      polymer and other hydrophobic phases can be determined easily and accurate. In
      this publication we report the determination of poly(dimethyl-siloxane) (PDMS)
      water, and Aldrich humic acid-water distribution coefficients for six PAHs with
      log K0w values varying from 4.56 to 6.85. The distribution coefficients to a PDMS
      fiber llog Kf) and the DOC (log KDOC) range from 3.86 to 5.39 and 4.78 to 7.43,
      respectively. Even for the most hydrophobic compounds, the distribution
      coefficients show small standard errors (< or = 0.05 log units). Therefore, this
      method might be applied to determine sorption coefficients of numerous, even more
      hydrophobic compounds, to humic acids as well as other dissolved hydrophobic
      matrixes.

PMID- 15952380
TI  - Evaluation of air acidity through optical sensors.
AB  - Optical sensors developed from dye-doped coatings obtained through the sol-gel
      method were designed and produced to evaluate air acidity. Both laboratory
      calibration and field test measurements in several locales of downtown Cracow,
      Poland, were undertaken with the aim of assessing the sensors' behavior. As a
      first approach, SO2 was considered as the main gaseous pollutant with acid
      properties capable of sensitizing the sensors under humid conditions. A
      relationship between the SO2 concentration measured by conventional automatic air
      pollution monitoring stations and the optical response of the sensors was
      established. To correlate such a relationship with the air acidity, a simple
      calculation, which also takes into account relative humidity, temperature, and
      atmospheric pressure, was done. Following this calculation, the sensors'
      detection threshold for pH was found to be 0.05, approximately. The sensors can
      be a very useful analytical tool to alert against acid rain risks in preventive
      conservation of historical materials, among other applications.

PMID- 15952381
TI  - Development of an immunoassay for the determination of polyaromatic hydrocarbons
      in plasma samples from oiled seabirds.
AB  - External exposure assessment of oiled seabirds is undertaken by assessment of the
      percentage oil coverage of the plumage. Nondestructive monitoring of the toxic
      fraction of petroleum oils and diesels (polyaromatic hydrocarbons, PAHs) which
      enters the general circulation (internal exposure burden) of oiled seabirds is
      rarely undertaken. This is because the traditionally used chromatographic methods
      for plasma PAH analysis require larger sample volumes than those that can be
      safely collected from smaller species, such as guillemots (Uria aalge).
      Furthermore, these methods are not a cost-effective or practical approach for
      analysis of large numbers of birds in a short time period as part of an oil spill
      response in wildlife rehabilitation centers. This study describes the
      modification and validation of a commercially available PAH immunoassay (cRaPID
      PAH) to enable high-throughput, cost-effective, simple, and rapid determination
      of total PAH concentrations in 50 microL volumes of plasma. The limit of
      detection of the assay was 0.1 ng/mL as benzo-apyrene (BaP) equivalents with a
      working range of 0.120 ng/mL. As further validation of the immunoassay, PAHs were
      determined by GC-MS. GC-MS data were significantly positively correlated with
      corresponding immunoassay data for the same birds (r2 = 0.976, p < 0.001). The
      plasma PAH concentrations of 40 oiled guillemots stranded on U.K. shores were
      determined using the assay to demonstrate its usefulness for biomonitoring
      studies. The mean ,PAH concentration observed was 1.05 +/- 0.67 ppm (range 0.02
      2.40 ppm as BaP equivalents). The modifications to the cRaPID PAH kit in this
      study enable nondestructive, high-throughput, semiquantitative determination of
      PAH concentrations in plasma samples suitable for exposure assessment of oiled
      seabirds during oil spill response and rehabilitation.

PMID- 15952382
TI  - Miniaturized lead sensor based on lead-specific DNAzyme in a nanocapillary
      interconnected microfluidic device.
AB  - A miniaturized lead sensor has been developed by combining a lead-specific
      DNAzyme with a microfabricated device containing a network of microfluidic
      channels that are fluidically coupled via a nanocapillary array interconnect. A
      DNAzyme construct, selective for cleavage in the presence of Pb2+ and derivatized
      with fluorophore (quencher) at the 5' (3') end of the substrate and enzyme
      strands, respectively, forms a molecular beacon that is used as the recognition
      element. The nanocapillary array membrane interconnect is used to manipulate
      fluid flows and deliver the small-volume sample to the beacon in a spatially
      confined detection window where the DNAzyme is interrogated using laser-induced
      fluorescence detection. A transformed log plot of the fluorescent signal exhibits
      a linear response (r2 = 0.982) over a Pb2+ concentration range of 0.1 - 100
      microM, and a detection limit of 11 nM. The sensor has been applied to the
      determination of Pb2+ in an electroplating sludge reference material, the result
      agreeing with the certified value within 4.9%. Quantitative measurement of Pb2+
      in this complex sample demonstrates the selectivity of this sensor scheme and
      points favorably to the application of such technologies to analysis of
      environmental samples. The unique combination of a DNAzyme with a microfluidic
      nanofluidic hybrid device makes it possible to change the DNAzyme to select for
      other compounds of interest, and to incorporate multiple sensing systems within a
      single device for greater flexibility. This work represents the initial steps
      toward creation of a robust field sensor for lead in groundwater or drinking
      water.

PMID- 15952383
TI  - Evaluating factors affecting the permeability of emulsions used to stabilize
      radioactive contamination from a radiological dispersal device.
AB  - Present strategies for alleviating radioactive contamination from a radiological
      dispersal device (RDD) or dirty bomb involve either demolishing and removing
      radioactive surfaces or abandoning portions of the area near the release point.
      In both cases, it is imperative to eliminate or reduce migration of the
      radioisotopes until the cleanup is complete or until the radiation has decayed
      back to acceptable levels. This research investigated an alternative strategy of
      using emulsions to stabilize radioactive particulate contamination. Emergency
      response personnel would coat surfaces with emulsions consisting of asphalt or
      tall oil pitch to prevent migration of contamination. The site can then be
      evaluated and cleaned up as needed. In order for this approach to be effective,
      the treatment must eliminate migration of the radioactive agents in the terror
      device. Water application is an environmental condition that could promote
      migration into the external environment. This research investigated the potential
      for water, and correspondingly contaminant, migration through two emulsions
      consisting of Topein, a resinous byproduct during paper manufacture. Topein C is
      an asphaltic-based emulsion and Topein S is a tall oil pitch, nonionic emulsion.
      Experiments included water adsorption/ mobilization studies, filtration tests,
      and image analysis of photomicrographs from an environmental scanning electron
      microscope (ESEM) and a stereomicroscope. Both emulsions were effective at
      reducing water migration. Conductivity estimates were on the order of 10(-80) cm
      s(-1) for Topein C and 10(-7) cm s(-1) for Topein S. Water mobility depended on
      emulsion flocculation and coalescence time. Photomicrographs indicate that Topein
      S consisted of greater and more interconnected porosity. Dilute foams of isolated
      spherical gas cells formed when emulsions were applied to basic surfaces. Gas
      cells rose to the surface and ruptured, leaving void spaces that penetrated
      throughout the emulsion. These experiments indicate that emulsions may be a
      viable means for containing RDD residuals; however, improvements are needed for
      optimal performance.

PMID- 15952384
TI  - Preparation of titania nanotubes and their environmental applications as
      electrode.
AB  - Titanium oxide nanotubes were successfully grown from a titanium plate by direct
      anodic oxidation with 0.2 wt % hydrofluoric acid being the supporting
      electrolyte. These nanotubes are of uniform size and are well-aligned into high
      density arrays. They look like honeywell with the structure similar to that of
      porous alumina obtained by the same technique. TiO2 anatase phase was identified
      by X-ray diffraction. Significant blue-shift in the spectrum of UV- vis
      absorption was observed. The mechanism of the novel, simple, and direct growth of
      the nanotubes was postulated. To investigate their potentials in environmental
      applications, degradation of pentachlorophenol (PCP) in aqueous solution was
      carried out using photoelectrocatalytic (PEC) processes, comparing with
      electrochemical process (EP) and photocatalytic (PC). A significant
      photoelectrochemical synergetic effect was observed. The kinetic constant of PEC
      degradation of PCP using TiO2 nanotubes electrode was 86.5% higher than that
      using TiO2 film electrode. In degrading PCP, 70% of TOC was removed using the
      TiO2 nanotubes electrode against 50% removed using TiO2 film electrode formed by
      sol-gel method in 4 h under similar conditions.

PMID- 15952385
TI  - Silicate enhanced enzymatic dehairing: a new lime-sulfide-free process for
      cowhides.
AB  - A conventional dehairing process with sodium sulfide and lime is a major source
      of the pollution from the tanning industry. In other words, conventional
      dehairing processes degrade the hair to the extent that it cannot be recovered;
      thus, these processes become a major contributor to wastewater pollution. In this
      study, an attempt has been made to develop a lime and sulfide-free dehairing
      process using a commercial enzyme formulation with the activation of a silicate
      salt. A dip and pile method of application has been standardized. The amount of
      enzyme and sodium metasilicate has also been optimized based on complete removal
      of hair. Enhancement of enzyme activity by the addition of silicate has been
      demonstrated through activity measurements. Hair removal is found to be complete
      using scanning electron microscope analysis. Strength and bulk properties of the
      experimental leathers are comparable to that of control leathers. The process
      enjoys a significant reduction in chemical oxygen demand (COD) and total solids
      (TS) by 53 and 26%, respectively. More importantly, the application of enzyme for
      dehairing results in an 8% area increase in the final leather. Also, the process
      is proven to be techno-economically feasible.

PMID- 15952386
TI  - Effects of pH and catalyst concentration on photocatalytic oxidation of aqueous
      ammonia and nitrite in titanium dioxide suspensions.
AB  - Batch experiments were conducted to study the effects of titanium dioxide (TiO2)
      concentration and pH on the initial rates of photocatalytic oxidation of aqueous
      ammonium/ ammonia (NH4+/NH3) and nitrite (NO2-) in UV-illuminated TiO2
      suspensions. While no simple kinetic model could fit the data at lower TiO2
      concentrations, at TiO2 concentrations > or = 1 g/L, the experimental data were
      consistent with a model assuming consecutive first-order transformation of
      NH4+/NH3 to NO2- and NO2- to nitrate (NO3-). For TiO2 concentrations > or = 1
      g/L, the rate constants for NO2 photocatalytic oxidation to NO3 were far more
      dependent on TiO2 concentration than were those for NH4+/NH3 oxidation to NO2-,
      suggesting that, without sufficient TiO2, complete oxidation of NH4+/NH3 to NO3-
      will not occur. Initial NH4+/NH3 photocatalytic oxidation rates were proportional
      to the initial concentrations of neutral NH3 and not total NH3(i.e., [NH4+] +
      [NH3]). Thus, the pH-dependent equilibrium between NH4+ and NH3, and not the pH
      dependent electrostatic attraction between NH4+ and the TiO2 surface, is
      responsible for the increase in rates of NH4+/NH3 photocatalytic oxidation with
      increasing pH. Electrostatic adsorption, however, can partly explain the pH
      dependence of the initial rates of NO2- photocatalytic oxidation. Initial rates
      of NO2- photocatalytic oxidation were 1 order of magnitude higher for NO2- versus
      NH4+/NH3, indicating thatthe rate of NH4+/NH3 photocatalytic oxidation to NO3-
      was limited by NH4+/NH3 oxidation to NO2- under our experimental conditions.

PMID- 15952387
TI  - Occurrence, sources, and fate of benzothiazoles in municipal wastewater treatment
      plants.
AB  - A set of six benzothiazoles was determined in effluents of three municipal
      wastewater treatment plants. Total concentrations of benzothiazoles ranged from
      1.9 to 6.7 microg/ L, with benzothiazole-2-sulfonate (BTSA) being most prominent
      (35 - 70%), followed by benzothiazole, 2-hydroxybenzothiazole, and 2-methylthi
      benzothiazole (MTBT). The removal of benzothiazoles in tertiary municipal
      wastewater treatment was investigated in more detail in one of the plants during
      two sampling periods of several weeks. Total benzothiazole concentration
      decreased by 5-28% only. This very limited removal was primarily due to BTSA and
      MTBT that were either hardly removed or even increased in concentration. In
      street runoff benzothiazoles exceeded the wastewater concentrations by 1 order of
      magnitude, showing that surface runoff can be a significant source of
      benzothiazole emission. In household wastewater total concentrations were in the
      range of 50-80% of that found in municipal wastewater. These investigations
      outline that benzothiazoles, a class of polar and biologically active industrial
      chemicals, are regularly released with treated municipal wastewater and exhibit a
      considerable lifetime in surface waters.

PMID- 15952388
TI  - Elucidation of degradation mechanism of dioxins during mechanochemical treatment.
AB  - Model dioxin compounds 4-chlorobiphenyl (4CB), octa-chlorodibenzo-p-dioxin
      (OCDD), and octachlorodibenzofuran (OCDF) were degraded by a mechanochemical (MC)
      process that involved milling with calcium oxide by use of a planetary ball mill.
      The degradation of 4CB produced mainly chloride ions and biphenyl, with the
      chlorine removal efficiency reaching about 100%. Biphenyl was transformed into
      terphenyls, quaterphenyls, cyclohexylbenzene, and bicyclohexyl through
      polymerization and hydrogenation reactions. Measurements of chloride ions after
      MC treatment of OCDD and OCDF showed about 100% dechlorination of both compounds;
      tetra- to heptachlorinated dibenzo-p-dioxins/furans (T4-H7CDD/Fs) were detected
      only at trace levels, and no other chlorinated organic compounds were observed.
      The residue after MC treatment was gray in color, indicating the possibility of
      carbonization, but the presence of amorphous graphite could not be confirmed.

PMID- 15952389
TI  - Electrochemical oxidation for low concentration of aniline in neutral pH medium:
      application to the removal of aniline based on the electrochemical polymerization
      on a carbon fiber.
AB  - Aniline, which causes serious environmental problems, was electrochemically
      treated and thereby removed from aqueous solution. This method demonstrated
      herein is based on the formation of polyaniline at an electrode surface by
      electrochemical oxidation. Initially, the electrode behavior of aniline at
      several conditions was investigated on a platinum, glassy carbon (GC), and carbon
      fiber (CF) electrode using voltammetric techniques. On the platinum electrode,
      aniline did not polymerize at low concentrations. However, electropolymerization
      of aniline was observed on both the GC and CF electrodes even at low
      concentrations in neutral pH solutions. The removal of aniline was carried out
      using a CF bundle with a large surface area. High removal efficiency for aniline
      was obtained by applying potentials greater than 0.8 V. Although generation of p
      benzoquinone as a byproduct was observed during electrochemical treatment, its
      generation was suppressed by applying a potential lower than 0.9 V. The cyclic
      voltammograms and X-ray photoelectron spectra of the CF after the treatment for
      aniline solution showed that polymeric aniline existed on the CF surface. The
      maximum surface coverage of electropolymerized aniline was estimated to be about
      1.49 x 10(-8) mol/cm2. Furthermore, the continuous treatment of aniline was
      demonstrated using a flow system.

PMID- 15952390
TI  - Influence of the order of reagent addition on NDMA formation during
      chloramination.
AB  - The formation of the potent carcinogen, N-nitrosodimethylamine (NDMA), during
      chlorine disinfection has caused significant concern among drinking water and
      wastewater recycling utilities practicing intentional or unintentional
      chloramination. Previous research modeled NDMA formation as arising from a
      reaction between monochloramine and organic nitrogen precursors, such as
      dimethylamine, via an unsymmetrical dimethylhydrazine (UDMH) intermediate.
      Contrary to the importance of monochloramine indicated by previous studies,
      hypochlorite formed an order of magnitude more NDMA than monochloramine when
      applied to a secondary municipal wastewater effluent containing excess ammonia.
      Experiments involving variation of the order that each reagent (i.e.,
      hypochlorite, ammonium chloride, and dimethylamine) was added to solution suggest
      two factors that may be more important for NDMA formation than the presence of
      monochloramine: (i) the chlorination state of organic nitrogen precursors and
      (ii) the partial formation of dichloramine. Although dichloramine formation was
      most influenced by the pH conditions under which inorganic chloramine formation
      was performed, mixing effects related to the order of reagent addition may be
      important at full-scale plants. Chloramination strategies are suggested that may
      reduce NDMA formation by nearly an order of magnitude.

PMID- 15952391
TI  - Continuous fermentative hydrogen production using a two-phase reactor system with
      recycle.
AB  - The effects of effluent recycle were examined in a two-phase anaerobic system
      where the first phase was operated for fermentative hydrogen production and the
      second for methanogenesis. The hydrogen reactor was operated as a chemostat at 35
      degrees C and pH 5.5 with a 10 h hydraulic retention time, and the methane
      reactor was operated as an up-flow reactor at 28 degrees C and pH between 6.9 and
      7.2. Two recycle ratios were examined: 0 and 0.98. Effluent recycle reduced the
      required alkalinity for pH control by approximately 40%. The H2 productivity
      metric, with a basis in electrons and incorporating both gaseous and dissolved
      H2, was developed as a more fundamental reporting method than the molar H2 yield.
      Without recycle, the H2 productivity was 0.115 g of H2 COD/g of feed COD, but
      decreased to 0.015 q of H2 COD/g of feed COD with recycle (COD = chemical oxygen
      demand). Mass balances indicated the lower H2 productivity during recycle was due
      to electrons being partitioned to methane and less-oxidized soluble constituents
      such as propionic acid, ethanol, and butanol. The results indicated that
      achieving high H2 productivity with nonsterile wastewaters will be challenging
      and membrane filtration of the recycle liquid may be required to exclude the
      return of hydrogen-consuming organisms.

PMID- 15952392
TI  - (E)-5-[2-(methoxycarbonyl)ethenyl]cytidine as a chemical actinometer for
      germicidal UV radiation.
AB  - (E)-5-[2-(Methoxycarbonyl)ethenyl]cytidine (S) was examined for use as a chemical
      actinometer for germicidal UV radiation. Its photoproduct, 3-beta-D-ribofuranosyl
      2,7-dioxopyrido[2,3-d]pyrimidine (P), is strongly fluorescent with excitation and
      emission maxima at 330 and 385 nm, respectively. Experiments were conducted to
      characterize the dynamic behavior of aqueous solutions of S and P when subjected
      to UV radiation. UV sources used for these experiments included a low-pressure
      mercury lamp, a XeBr excimer lamp, and a KrCI excimer lamp; all three sources
      were mounted in collimating devices to provide incident beams that could be
      easily and accurately characterized by radiometry. These three sources each
      yielded essentially monochromatic outputwith characteristic wavelengths of 254,
      282, and 222 nm, respectively. At practical concentrations, it was found that the
      absorbance of the actinometer solution was neither high enough to make the
      actinometer solutions optically opaque nor low enough to be optically transparent
      to UV. In addition, the photoproduct displayed a molar absorption coefficient
      that was similar in magnitude to that of the parent compound, thereby resulting
      in competitive absorption of UV energy between Sand Pduring irradiation. For
      purposes of evaluation of the results of irradiation, a mathematical model was
      developed to accountforthe nonideal optical characteristics of the system. The
      model is based on a description of local photochemical kinetics; predictions of
      overall reactor performance were developed by spatial and temporal integration of
      model results. The model was used to analyze the dynamic behavior of actinometer
      solutions during UV irradiation and to estimate the quantum yield for
      photoproduction of Pfrom S. This modeling approach is potentially applicable to
      other photochemical processes in which multiple compounds are present that absorb
      photoactive radiation; however, general application of this modeling approach to
      photochemical reactor systems will require inclusion of othertermsto describe
      relevanttransport behavior within the system.

PMID- 15952393
TI  - Preparation and evaluation of GAC-based iron-containing adsorbents for arsenic
      removal.
AB  - Granular activated carbon-based, iron-containing adsorbents (As-GAC) were
      developed for effective removal of arsenic from drinking water. Granular
      activated carbon (GAC) was used primarily as a supporting medium for ferric iron
      that was impregnated by ferrous chloride (FeCl2) treatment, followed by chemical
      oxidation. Sodium hypochlorite (NaClO) was the most effective oxidant, and
      carbons produced from steam activation of lignite were most suitable for iron
      impregnation and arsenic removal. Two As-GAC materials prepared by FeCl2
      treatment (0.025 -0.40 M) of Dacro 20 x 50 and Dacro 20 x 40LI resulted in a
      maximum impregnated iron of 7.89% for Dacro 20 x 50 and 7.65% for Dacro 20 x
      40Ll. Nitrogen adsorption-desorption analyses showed the BET specific surface
      area, total pore volume, porosity, and average mesoporous diameter all decreased
      with iron impregnation, indicating that some micropores were blocked. SEM studies
      with associated EDS indicated that the distribution of iron in the adsorbents was
      mainly on the edge of As-GAC in the low iron content (approximately 1% Fe) sample
      but extended to the center at the higher iron content (approximately 6% Fe). When
      the iron content was > approximately 7%, an iron ring formed at the edge of the
      GAC particles. No difference in X-ray diffraction patterns was observed between
      untreated GAC and the one with 4.12% iron, suggesting that the impregnated iron
      was predominantly in amorphous form. As-GAC could remove arsenic most efficiently
      when the iron content was approximately 6%; further increases of iron decreased
      arsenic adsorption. The removal of arsenate occurred in a wide range of pH as
      examined from 4.4 to 11, but efficiency was decreased when pH was higher than
      9.0. The presence of phosphate and silicate could significantly decrease arsenate
      removal at pH > 8.5, while the effects of sulfate, chloride, and fluoride were
      minimal. Column studies showed that both As(V) and As(III) could be removed to
      below 10 microg/L within 6000 empty bed volume when the groundwater containing
      approximately 50 microg/L of arsenic was treated.

PMID- 15952395
TI  - Iron(VI) and iron(V) oxidation of copper(I) cyanide.
AB  - Copper(Il) cyanide (Cu(CN)4(3-)) in the gold mine industry presentsthe biggest
      concern in cyanide management because it is much more stable than free cyanide.
      Cu(CN)4(3-) is highlytoxic to aquatic life; therefore, environmentally friendly
      techniques are required for the removal of Cu(CN)4(3-) from gold mine effluent.
      The oxidation of Cu(CN)4(3-) by iron-(VI) (FeVIO4(2-), Fe(VI)) and iron(V)
      (FeVO4(3-), Fe(V)) was studied using stopped-flow and premix pulse radiolysis
      techniques. The stoichiometry with Fe(VI) was determined to be 5HFeO(4-) +
      Cu(CN)4(3-) + 8H2O - > 5Fe(OH)3 + Cu2+ + 4CNO- +3/202 + 6OH-. The rate law for
      the oxidation of Cu(CN)4(3-) by Fe(VI) was found to be first-order with each
      reactant. The rates decreased with increasing pH and were mostly related to a
      decrease in concentration of reactive protonated Fe(VI) species, HFeO4-. A
      mechanism is proposed that agrees with the observed reaction stoichiometry and
      rate law. The rate constant for the oxidation of Cu(CN)4(3-) by Fe(V) was
      determined at pH 12.0 as 1.35 +/- 0.02 x 10(7) M(-1) s(-1), which is
      approximately 3 orders of magnitude larger than Fe(VI). Results indicate that
      Fe(VI) is highly efficient for removal of cyanides in gold mill effluent.

PMID- 15952394
TI  - Reactivation of a commercial diesel oxidation catalyst by acid washing.
AB  - The catalytic activity of samples taken from an oxidation catalyst mounted on
      diesel-driven automobiles and aged under road conditions was recovered to a
      significant extent by washing with a dilute solution of citric acid. The
      characterization of samples arising from a fresh, a vehicle-aged, and a
      regenerated catalyst was carried out by scanning electron microscopy (SEM-EDS), X
      ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). Relatively
      high levels of S and P, in the form of aluminum sulfate and phosphate,
      respectively, together with contaminant Si were detected in the used catalyst.
      Washing of the vehicle-aged catalytic oxidation converter revealed high
      efficiency in the extraction of the main contaminants detected (S and P) by this
      nondestructive methodology. The results of the experiments reported here should
      encourage the development of a technology based on this reactivation procedure
      for the rejuvenation of the catalytic device mounted on diesel exhaust pipes.

PMID- 15952396
TI  - Novel incineration technology integrated with drying, pyrolysis, gasification,
      and combustion of MSW and ashes vitrification.
AB  - The conventional mass burn systems for municipal solid waste (MSW) emit large
      amount of acidic gases and dioxins as well as heavy metals due to the large
      excess air ratio. Additionally, the final process residues, bottom ash with
      potential leachability of heavy metals and fly ash with high level of heavy
      metals and dioxins, also constitute a major environmental problem. To deal with
      these issues more effectively, a novel MSW incineration technology was developed
      in this study. MSW drying, pyrolysis, gasification, incineration, and ash
      vitrification were achieved as a spectrum of combustion by the same equipment
      (primary chamber) in one step. In practice, the primary chamber of this
      technology actually acted as both gasifier for organic matter and vitrifying
      reactor for ashes, and the combustion process was mainly completed in the
      secondary chamber. Experiments were carried outto examine its characteristics in
      an industrial MSW incineration plant, located in Taiyuan, with a capability of
      100 tons per day (TPD). Results showed that (1) the pyrolysis, gasification, and
      vitrification processes in the primary chamber presented good behaviors resulting
      in effluent gases with high contents of combustibles (e.g., CO and CH4) and
      bottom ash with a low loss-on-ignition (L.o.l), low leachability of heavy metals,
      and low toxicity of cyanide and fluoride. The vitrified bottom ash was benign to
      its environment and required no further processing for its potential
      applications. (2) Low stack emissions of dioxins (0.076 ng of TEQ m(-3)), heavy
      metals (ranging from 0.013 to 0.033 mg m(-3)), and other air pollutants were
      achieved. This new technology could effectively dispose Chinese MSW with a low
      calorific value and high water content; additionally, it also had a low capital
      and operating costs compared with the imported systems.

PMID- 15952397
TI  - Influence of flocculation and adsorption as pretreatment on the fouling of
      ultrafiltration and nanofiltration membranes: application with biologically
      treated sewage effluent.
AB  - Membrane fouling is a critical limitation on the application of membranes to
      wastewater reuse. This work aims to understand the fouling phenomenon which
      occurs in ultrafiltration (UF; 17500 molecular weight cutoff (MWCO)) and
      nanofiltration (NF; 250 MWCO) membranes, with and without pretreatment. For this
      purpose, the molecular weight (MW) distribution of the organics has been used as
      a parameter to characterize the influent, the permeate, and the foulant on the
      membrane surface. The variation of foulant concentration on the membrane due to
      pretreatment of the influent by flocculation and/or adsorption was investigated
      in detail. With the UF membrane, the peak of the MW distribution of organics in
      the permeate depended on the pretreatment; for example, the weight-averaged MW
      (Mw) of 675 without pretreatment shifted down to 314 with pretreatment. In the
      case of the NF membrane, the Mw of organics in the permeate was 478 (without
      pretreatment) and 310 (with flocculation followed by adsorption). The Mw of the
      organics in the foulant on the membrane surface was 513 (UF) and 192 (NF) without
      pretreatment and 351 (UF) and 183 (NF) after pretreatment with flocculation
      followed by adsorption, respectively. Without the pretreatment, the foulant
      concentration was higher on both membranes. The difference was more significant
      on the UF membrane than on the NF membrane. For both membranes, the flocculation
      and-then-adsorption pretreatment proved very effective.

PMID- 15952398
TI  - Thermal degradation of PCDD/F in municipal solid waste ashes in sealed glass
      ampules.
AB  - Due to their high concentrations of toxic organic compounds such as
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/F), metals, and water
      soluble salts, fly ashes are classified as hazardous waste in the European Union
      and are required to be deposited in controlled landfills. We have shown here that
      the tetra- to octachlorinated PCDD/F in fly ash can be degraded by thermal
      treatment. The temperature needed for total degradation of PCDD/F depends on the
      composition of the fly ash. Its concentrations of unburned carbon and alkaline
      compounds were found to be important in this respect. Experimental design was
      used to investigate the effects of varying the temperature, residence time, and
      atmosphere on the degradation of PCDD/F in three different types of fly ash. The
      results showed that the three ashes clearly showed different degradation
      potentials for PCDD/F during thermal treatment. The concentrations of unburned
      carbon, alkaline species such as CaO and Na2O, and metals such as copper and iron
      strongly influenced the degradation of PCDD/F. However, the different
      combinations of pH and amounts of native PCDD/F, unburned carbon, metals (Cu, Fe,
      Sn and Na), and sulfur in the ashes made it difficult or even impossible to
      conclude that any single parameter was responsible for the degradation of PCDD/F
      in these thermal treatment experiments. The decreases observed in all of the
      experiments are due to dechlorination and/or destruction of PCDD/F: depending on
      the temperature and ash composition, either of these processes may be the more
      important.

PMID- 15952399
TI  - Exergy-based efficiency and renewability assessment of biofuel production.
AB  - This study presents an efficiency and renewability analysis of the production of
      three biofuels: rapeseed methyl ester (RME), soybean methyl ester (SME) and corn
      based ethanol (EtOH). The overall production chains have been taken into account:
      not only the agricultural crop production and the industrial conversion into
      biofuel, but also production of the supply of agricultural resources (pesticides,
      fertilizers, fuel, seeding material) and industrial resources (energy and
      chemicals) to transform the crops into biofuel. Simultaneously, byproducts of the
      agricultural and industrial processes have been taken into account when resources
      have to be allocated to the biofuels. The technical analysis via the second law
      of thermodynamics revealed that corn-based EtOH results in the highest production
      rate with an exergetic fuel content of 68.8 GJ ha(-1) yr(-1), whereas the RME and
      SME results were limited to 47.5 and 16.4 GJ ha(-1) yr(-1). The allocated
      nonrenewable resource input to deliver these biofuels is significant: 16.5, 15.4,
      and 5.6 MJ ha(-1) yr(-1). This means that these biofuels, generally considered as
      renewable resources, embed a nonrenewable fraction of one-quarter for EtOH and
      even one-third for RME and SME. This type of analysis provides scientifically
      sound quantitative information that is necessarywith respect to the
      sustainability analysis of so-called renewable energy.

PMID- 15952400
TI  - Comment on "Detection of perfluorooctane surfactants in Great Lakes water" and
      "Mass budget of perluorooctane surfactants in Lake Ontario".

PMID- 15952401
TI  - Plasma leptin concentration increases early during highly active antiretroviral
      therapy for acquired immunodeficiency syndrome, independent of body weight.
AB  - Leptin, the protein product of the obese gene (ob), is secreted by adipocytes.
      Circulating leptin levels correlate with fat mass in humans, including
      individuals infected with HIV. Leptin serves as an adipostatic hormone, a
      permissive factor for reproduction and a modulator of immune function. Leptin is
      a cytokine, and has been demonstrated to enhance CD4 cell proliferation and IL-2
      secretion from CD4 cells in vitro. The role of leptin in HIV-positive patients
      treated with highly active antiretroviral therapy (HAART) has not been well
      defined. We haveevaluated leptin levels in HIV-infected individualsduringthe
      early phase of HAART. We measured plasma leptin levels in 15 antiretroviral-naive
      HIV positive patients at baseline and after 1 and 4 weeks of HAART. After the
      first week of therapy, mean leptin level and CD4 count were increased compared to
      baseline, 6.0 vs 7.2 ng/ml (p = 0.004) and 377 vs 432 cells/ul (p = 0.014),
      respectively. In contrast, mean body mass index (BMI) remained unchanged 27.0 vs
      26.8 kg/m2 (p < 0.08). After four weeks of therapy, leptin and BMI values were
      unchanged compared to baseline, 6.0 vs 5.9 (p < 0.4) and 27.0 vs 26.9 (p < 0.5),
      respectively, whereas CD4 count continued to increase to 491 cells/ul (p < 0.012
      compared to baseline). These data demonstrate an early transient increase in
      plasma leptin levels in HIV positive patients initiated on HAART, despite a lack
      of change in BMI. It is unclear if the transient increase in leptin is related to
      its role as a cytokine, a metabolic regulator, or reproductive factor.

PMID- 15952402
TI  - Effects of neridronate treatment in elderly women with osteoporosis.
AB  - Osteoporosis is a common disorder, especially among elderly post-menopausal
      women. Elderly women are often affected by co-morbidities, impaired
      gastrointestinal function and reduced mobility; therefore, the treatment strategy
      for their osteoporosis can be difficult. In this randomized pilot study, we have
      investigated the effects of a 12-month treatment with neridronate on bone mineral
      density (BMD), bone turnover markers and quality of life (QoL). The study
      included 40 women (age, 65-80 yr; post-menopausal period, >15yr) from a single
      osteoporosis centre. Twenty women received a monthly im injection of 25 mg of
      neridronate associated with a daily dose of 500 mg of calcium and 400 U of
      vitamin D. Twenty women received calcium plus vitamin D supplements alone.
      Changes in BMD at the lumbar spine and femoral neck were measured by dual energy
      X-ray absorptiometry. Serum type I collagen C-telopeptide (sCTX), urinary free
      deoxypyridinoline (ufDPD), bone alkaline phosphatase (ALP) and serum osteocalcin
      levels were determined. For the QoL assessment, the Italian version of the SF-36
      test was administrated. Spine and hip BMD rose by 6.6 +/- 3 and 4.2 +/- 2.3%,
      respectively (p < 0.05), after 12 months of neridronate treatment. Markers of
      skeletal turnover significantly fell already after 3 months of neridronate
      treatment and decreased progressively thereafter within 12 months. The mean
      decrease at 12 months ranged from 38 +/- 11% for sCTX to 25.2 +/- 15% for ufDPD
      (p < 0.001, all). The mean improvement in QoL in the treated group was 45.7% for
      bodily pain, 37.5% for general health perception, 23.1% for vitality, 18% for
      emotional role functioning and 12% for physical role functioning. The changes
      observed in BMD, turnover markers and QoL in the untreated group were ns. The
      intermittent neridronate administration was easily manageable and well tolerated.
      In conclusion, neridronate currently represents a valid option for the treatment
      of osteoporosis, since it helps just as much as oral BPs in the improvement of
      BMD and in particular conditions it can be even more effective.

PMID- 15952403
TI  - Evaluation of autonomic activity in patients with subclinical hypothyroidism.
AB  - It has been shown that impaired cardiac autonomic activity is closely related
      with lethal arhythmias. Heart rate variability (HRV), analysis of beat-to-beat
      variations, is an important and widely used non-invasive method to assess
      autonomic function. Impaired cardiac autonomic activity and altered sympathovagal
      balance were previously documented in patients with hypothyroidism. However, the
      effect of subclinical hypothyroidism (SH) on autonomic function has not been
      studied yet. We aimed to investigate the effect of SH on sympathovagal balance
      using the HRV method. The study included 31 patients with SH and 28 healthy
      volunteer controls. Patients with cardiac, metabolic, neurological disease or any
      other systemic disease that could affect autonomic activity were excluded from
      the study. HRV time domain and frequency domain parameters were determined over a
      period of 24 h. All time and frequency domain measures of HRV in patients with SH
      were not significantly different compared to those of healthy control group (p >
      0.05). Additionally, we compared SH subgroups (TSH level > or =10 and TSH level
      <10 mU/l) with each other and the controls. A statistically significant
      difference was observed only in time domain parameters of SD of normal-to-normal
      intervals (SDNN) and SD of all 5-min mean normal NN intervals (SDANN) between
      subgroup with TSH level > or =10 and controls (p < 0.05, p < 0.05, respectively).
      In correlation analysis with TSH, there was positive relationship between TSH and
      the root mean square of successive differences between adjacent R-R intervals
      (rMSSD). These findings indicate that SH may affect cardiac autonomic activity in
      correlation with TSH levels.

PMID- 15952404
TI  - Helicobacter pylori prevalence in diabetic patients and its relationship with
      dyspepsia and autonomic neuropathy.
AB  - AIMS: We evaluated the prevalence of Helicobacter pylori (HP) in Type 2 diabetic
      patients and its relationship with dyspeptic symptoms and complications of
      diabetes. MATERIALS AND METHODS: Seventy-eight Type 2 diabetic patients (54
      females, 24 males, mean age: 51.9 +/- 10.6 yr) and 71 non-diabetic control
      subjects were involved in the study. Patients were questioned for dyspeptic
      symptoms. Cardiovascular autonomic neuropathy, nephropathy and retinopathy were
      investigated in diabetic patients. Upper gastrointestinal tract endoscopy was
      performed for all patients and gastric biopsies were obtained and searched for
      HP. RESULTS: Helicobacter pylori prevalence was significantly higher in diabetic
      patients than in control subjects (75.6 vs 46%, p < 0.05). No differences were
      found between women and men with regard to HP infection status in diabetic
      patients. There was no relation between HP and diabetic complications,
      nephropathy and retinopathy. Helicobacter pylori prevalence was significantly
      higher in diabetic patients with cardiovascular autonomic neuropathy than in
      diabetic patients without cardiovascular autonomic neuropathy (90.6 vs 44.0%, p <
      0.02). Forty-seven subjects with diabetes had symptoms of dyspepsia (60.3%) and
      the prevalence of HP was higher in these patients (p < 0.002). CONCLUSION: There
      is a high prevalence of HP infection in diabetic patients and it is correlated
      with dyspeptic symptoms. Diabetic subjects complicated with cardiovascular
      autonomic neuropathy and dyspepsia are at high risk of HP infection and should be
      carefully investigated and considered for eradication therapy.

PMID- 15952405
TI  - Long-term potassium citrate therapy and bone mineral density in idiopathic
      calcium stone formers.
AB  - Several authors have described an association between idiopathic calcium (Ca)
      stone disease and bone mass reduction. Hypocitraturia is a frequent feature of
      urolithiasis, and alkaline citrate has been recommended as one of the choice
      treatments in this disease. Some evidence exists as to the positive effect of
      potassium (K) citrate therapy on bone mass. The aim of this work was the
      longitudinal evaluation of bone mineral density (BMD) changes in a group of Ca
      oxalate stone formers treated with K citrate for two years. Enrolled patients
      were 120; 109 subjects completed the study (51 males and 58 females). A metabolic
      study and distal radius BMD measurements were conducted both at baseline (BAS)
      and at the end of the study (END). BMD (0.451 +/- 0.081 vs 0.490 +/- 0.080
      g/cm2), T-score (-1.43 +/- 1.02 vs -0.90 +/- 1.04), net gastrointestinal alkali
      absorption (40.37 +/- 50.57 vs 61.26 +/- 42.26 mEq/day), urinary citrate (2.53 +/
      1.15 vs 3.10 +/- 1.44 mmol/day) and K (58.93 +/- 22.28 vs 65.45 +/- 23.97
      mmol/day) excretion significantly increased from BAS to END. Urinary Ca excretion
      remained unchanged from BAS to END (5.16 +/- 2.74 vs 5.57 +/- 2.85 mmol/ day).
      Our results indicate that long-term treatment with K citrate increases forearm
      BMD in idiopathic Ca stone formers. It seems probable that the alkali load
      provided by this drug reduces bone resorption by a buffering of the endogenous
      acid production. K citrate appears to be a further therapeutic opportunity for
      the management of osteoporosis in Ca stone formers.

PMID- 15952406
TI  - Advanced glycosylation end products in skin, serum, saliva and urine and its
      association with complications of patients with type 2 diabetes mellitus.
AB  - BACKGROUND: The accumulation of advanced glycation end products (AGEs) has a key
      role in the pathophysiology of diabetes complications. Comparison of AGEs
      measurement in serum, skin, saliva and urine has not been reported. AIMS: To
      compare AGEs in serum, skin, saliva and urine in patients with Type 2 diabetes
      mellitus, with complications at different stages. MATERIALS AND METHODS: We
      examined 50 patients with Type 2 diabetes mellitus (40 women and 10 men) grouped
      according to the progression of neuropathy, nephropathy and retinopathy. The AGEs
      content in serum, skin, saliva and urine was measured by spectrofluorometry HPLC.
      RESULTS: The patients had a mean age of 56.5 +/- 7.7 yr and 12.8 +/- 6.7 yr since
      diagnosis. AGEs in skin correlated with years since diagnosis (p = 0.0005). AGEs
      in serum, skin and saliva increased with the progression of complications,
      nevertheless, in urine a trend to diminution was found. In the group with end
      stage renal disease (ESRD), AGEs in serum increased in greater proportion. In
      order to account for the decreased AGEs clearance, we corrected the values for
      creatinine levels, and AGEs in skin gave a better association with complications.
      CONCLUSIONS: The AGEs measurement in skin, serum and saliva are useful to
      evaluate diabetes complications. AGEs in skin are associated with years since
      diagnosis of diabetes. Correction for renal function might discriminate AGEs in
      situ formation from accumulation.

PMID- 15952407
TI  - Bone mineral density at diagnosis and following successful treatment of pediatric
      Cushing's disease.
AB  - Bone mineral density (BMD) is frequently reduced in children and adolescents with
      Cushing's disease (CD), but there is little follow-up data after cure. BMD was
      determined by dual energy X-ray absorptiometry (DEXA) in two groups of patients
      with CD. Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2
      16.8), assessed at diagnosis. Group 2 comprised 11 subjects, 6 males and 5
      females, diagnosed at age 13.3 yr (6.4-17.4), cured by transsphenoidal surgery
      (TSS) (no.=7) or TSS + pituitary irradiation (no.=4). They had measurement of
      BMD, at mean age of 18.3 yr (11.1-28.5), i.e. 4.5 yr (0.8-11.4) after cure. Four
      patients, mean age 20.2 yr (17.6-22.4), had repeated DEXA'scans, 1-4 times, for
      up to 5.8 yr. After cure, GH deficiency was present in 9 patients and treated
      with hGH in 8. In Group 1, patients' L2-L4 volumetric (v)BMD Z-score was variable
      with a mean of -1.04 (-3.21-0.11). L2-L4 vBMD Z-score values correlated
      negatively with midnight cortisol (p < 0.05). In Group 2, mean L2-L4 vBMD was 
      0.38 (-1.0-0.13); and in 7/11, mean femoral neck (FN) areal (a)BMD Z-score was
      0.14 (-1.62-2.46). FN aBMD Z-score was higher than L2-L4 aBMD Z-score (p < 0.05).
      In patients with repeated scans, mean change in L2-L4 vBMD Z-score was 0.20 (
      0.15-0.45), and mean change in FN aBMD Z-score 0.03 (-0.53-0.38). These findings
      show variability of BMD at diagnosis and near normal BMD after cure of pediatric
      CD, suggesting that with appropriate replacement of pituitary hormone deficiency
      normal peak bone mass is achievable.

PMID- 15952408
TI  - Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after
      one month withdrawal of long-term therapy with aldosterone-receptor antagonist
      potassium canrenoate.
AB  - We have re-evaluated 15 patients with idiopathic primary aldosteronism one month
      after withdrawal of therapy with aldosterone-receptor antagonist potassium
      canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the
      sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110
      mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125
      160/80-100 mmHg). One month after withdrawal, the ratio aldosterone
      (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased
      only in 3 cases (median 18, range 6.1-125). We found a significant inverse
      correlation between the upright aldosterone/plasma renin activity (aldo/PRA)
      ratio, 1 month after withdrawal, and the number of years of therapy with
      potassium canrenoate. We conclude that long-term therapy with the aldosterone
      receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many
      cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the
      drug. These data are consistent with possible regression of idiopathic primary
      hyperaldosteronism after long-term therapy with potassium canrenoate, or in
      alternative to a persistent effect of potassium canrenoate, on aldosterone
      synthesis.

PMID- 15952409
TI  - Short-term modification of sex hormones is associated with changes in ghrelin
      circulating levels in healthy normal-weight men.
AB  - The aim of this study was to evaluate the effect of selective and short-term sex
      hormone modifications on ghrelin levels in normal-weight eugonadal men undergoing
      hormonal contraceptive treatments. Seven men received an oral progestin
      [cyproterone acetate (CPA) or dienogest (DNG)] 10 mg/day for 3 weeks (CPA-DNG
      group), 7 CPA orally 5 mg/day in association with testosterone enanthate (TE) im
      200 mg/week for 8 weeks (CPA-TE group), and 7 placebo (PLAC) for 8 weeks (PLAC
      group). Anthropometry and blood levels of LH, FSH, testosterone, estradiol,
      glucose, insulin and total ghrelin were evaluated. At baseline, no parameters
      differed among the three groups. After treatment, LH and FSH decreased in both
      CPA-DNG and CPA-TE groups, whereas they did not change in the PLAC group.
      Testosterone and estradiol decreased in the CPA-DNG group to the hypogonadal
      range, increased in the CPA-TE group to supraphysiological concentrations and, as
      expected, remained unchanged in the PLAC group. Total ghrelin levels increased in
      the CPA-DNG, decreased in the CPA-TE and did not change in the PLAC group. Ns
      modifications in the other parameters were observed in any group, demonstrating
      that the short-term changes of circulating sex hormones are able to modify
      ghrelin levels. These data, therefore, suggest that sex steroids are important
      regulators of ghrelin in normal-weight healthy men too.

PMID- 15952410
TI  - Different degrees of GH deficiency evidenced by GHRH+arginine test and IGF-I
      levels in adults with pituritary disease.
AB  - To verify if the entity of the peak GH responses to the GHRH+arginine (ARG) test
      is able to show different degree forms of GH deficiency (GHD), we linked these
      responses with the number of other anterior pituitary deficits. These anterior
      pituitary deficits were also related with IGF-I levels. To this purpose, we
      studied a large cohort of lean patients with pituitary disease of different
      etiologies [86 males and 68 females; age: mean +/- SEM 41.5 +/- 1.2 yr, body mass
      index (BMI) <25 kg/m2]. The patients were subdivided into 4 groups according to
      the increasing number of hormone deficiencies: isolated GHD (HYPO1, no.=28) or
      GHD plus one, two or three additional hormones (gonadotrophin, ACTH, and TSH)
      deficiencies (HYPO2, no.=20; HYPO3, no.=15; HYPO4, no.=91). Peak GH responses to
      the GHRH+ARG test and IGF-I levels showed a clear difference among the groups (p
      < 0.01 and p < 0.001, respectively). A significant difference was found between
      HYPO1 and HYPO4 for IGF-I levels (p < 0.05), and between HYPO1 and HYPO4 and
      between HYPO2 and HYPO4 for the GHRH+ARG test (p < 0.005). Considering only the
      patients who underwent both GHRH+ARG test and insulin tolerance test (ITT)
      (no.=70), the pattern of the peak GH responses to the GHRH+ARG test was the same
      of the whole group of patients, while no statistical difference was found with
      ITT. Our data show that the peak GH responses to the GHRH+ARG test and the IGF-I
      levels are linked to the severity of hypopituitarism, expressed by the number of
      increasing anterior pituitary deficits. This association is lost if the
      evaluation of the GH status is performed by the ITT. In all, the GHRH+ARG test
      and measurement of IGF-I are able to evidence different degrees of GHD in adult
      patients with pituitary disease.

PMID- 15952411
TI  - Ascorbic acid inhibits osteoclastogenesis of RAW264.7 cells induced by receptor
      activated nuclear factor kappaB ligand (RANKL) in vitro.
AB  - Ascorbic acid (AA) plays a key role in the regulation of differentiation and
      activation of osteoclast (OCL). It was reported that AA might induce the
      formation of OCL in cocultures of mouse bone marrow cells and ST2 cells, but it
      is not clear whether AA has a direct impact on the OCL precursors. The purpose of
      this study was to examine the effect of AA on the differentiation of OCL
      precursor RAW264.7 cells, cultured with receptor-activated nuclear factor kappaB
      ligand (RANKL). The results showed that AA remarkably inhibited the cell
      proliferation at a higher concentration and RANKL alone is sufficient for
      osteoclastogenesis. The expression of carbonic anhydrase (CAII) mRNA and protein,
      the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated
      cells (MNCs), and the percentage area of resorption lacunae induced by RANKL were
      decreased when AA was added to the cultures. The results demonstrate that AA
      inhibits RANKL-induced differentiation of OCL precursor cells into mature OCL and
      reduces the formation of bone resorption pits in vitro.

PMID- 15952412
TI  - The effect of cervical X-irradiation on activity index of thyrocytes and plasma
      TSH: a pre-clinical model for radiation-induced thyroid damage.
AB  - Because radiotherapy in the head and neck region is necessary in the treatment of
      childhood cancer, possibilities to prevent damage to the thyroid gland must be
      explored. We developed a model in which radiation-induced effects can be
      investigated in a way that these effects can be quantified, using thyroid
      dysmorphology and plasma TSH. Thirty-five Wistar rats, 5 weeks old, were X
      irradiated on the cervical region, with a single dose varying from 0 to 20 Gy.
      After 6 weeks, TSH, T4 and T3 were determined, and thyroid glands were processed
      for histological examination by two independent pathologists. A histological
      classification scale was developed, using follicular size, colloid density and
      cell height of thyrocytes to measure hyperplasia and hypertrophy. By the sum of
      these scores, a cell-activity index was calculated, which was related to plasma
      TSH concentration. Numbers of PAS-positive droplets and epithelial desquamation
      were also counted. Inter-observer reliability was assessed. Good to very good
      reliability was found for scores of follicular size, colloid density and cell
      height. Significant increase of cell-activity index was found after 10, 15 and 20
      Gy. The plasma TSH concentration was positively correlated to the cell-activity
      index, increasing with radiation-doses up to 15 Gy. The number of desquamated
      cells was significantly increased after radiation doses >10 Gy, with moderate
      reliability. In conclusion, this model using cell-activity index of thyrocytes
      together with plasma thyrotropin concentrations and desquamation of cells can be
      used for interpretation and future (pre-clinical) studies of prevention of
      radiation-induced thyroid damage.

PMID- 15952413
TI  - Successful use of recombinant human thyrotropin in the therapy of pediatric well
      differentiated thyroid cancer.
AB  - Recombinant human TSH (rhTSH) is increasingly employed in stimulating radioiodine
      (131I) uptake in adults with well-differentiated thyroid cancer (WDTC) for
      diagnostic scanning, and preliminary evidence suggests that it may have a role in
      radioactive iodine therapy as well. However, the safety and efficacy of rhTSH in
      children have not been determined. We report a case of a 13-yr-old boy presenting
      with metastatic papillary thyroid cancer. After total thyroidectomy, his serum
      thyroglobulin (Tg) was 302 ng/ml (3.7-49.3) with negative antibodies. A
      diagnostic whole body scan (WBS) demonstrated multiple foci of uptake in the
      neck, thyroid bed and chest. His serum TSH only increased to 14.2 microU/ml (0.3
      4.7) upon thyroid hormone withdrawal. Therefore, the patient was given 0.9 mg
      rhTSH every 24 h for two consecutive days and treated with 102 mCi 131I 24 h
      after the last rhTSH injection. Six months later, the patient was again
      conditioned with rhTSH and treated with an additional 150 mCi 131I. This
      treatment effectively reduced his tumor load with his most recent (10 months
      after the second ablation) serum Tg measuring 19.3 ng/ml. This case highlights
      the safety and effectiveness of rhTSH stimulated radioablation in pediatric WDTC,
      and proposes to invite controlled studies to further investigate pediatric rhTSH
      use, particularly in patients in whom thyroid hormone withdrawal is not a viable
      option.

PMID- 15952414
TI  - Final height in a patient with Laron syndrome after long-term therapy with rhlGF
      I and short-term therapy with LHRH-analogue and oxandrolone during puberty.
AB  - OBJECTIVE: To report our experience on long-term treatment with recombinant-human
      IGF-I (rhIGF-I) of a female patient with Laron syndrome (mutation G223G in the GH
      receptor gene), who received short-term treatment (1 yr) with LHRH analogue at
      the start of puberty and subsequently with oxandrolone. CASE REPORT: The patient
      started IGF-I therapy (dose 40 microg/kg bid for 9 months, 80 microg/kg bid until
      13.7 yr of age and 120 microg/kg bid thereafter) when she was 7.6 yr old (height 
      6 sds), and was treated for 9.4 yr until final height (cm 129.7; -5.5 sds). At
      first signs of puberty (age 12.7 yr; height 116.3; -5.3 sds), LHRH analogue was
      started (3.75 mg/28 days) and bone age progressed by 6 months in the 12-month
      period. Growth velocity decreased in the 6-12th month of combined treatment (0.9
      cm/6 months), and treatment was suspended. At age 14.8 (height 124.5; -6.6 sds),
      oxandrolone was added (0.1 mg/kg/day), but after 12 months (height 128 cm; -5.7
      sds) bone age increased from 11.5 to 13.5 yr and the drug was stopped. No side
      effects occurred during the various treatments. Body segments progressed
      harmonically: there was a tendency towards improvement in the upper to lower body
      segment ratio and in cranial growth. Only biiliac diameter did not increase
      during LHRH treatment. During the 9-yr period, body mass index (BMI), subscapular
      and triceps skinfold centiles did not show any significant variations.
      CONCLUSIONS: Our patient with Laron syndrome after long-term treatment showed a
      final result below the initial expectations, confirming that IGF-I used with the
      present schedule is less effective than GH in GH-deficient patients. LHRH
      analogue therapy at puberty was associated with a slower bone age maturation but
      with an almost complete arrest of growth. On the contrary, oxandrolone sustained
      growth but caused an excessive maturation of bone age. Other strategies are
      necessary to improve final height in these patients.

PMID- 15952415
TI  - Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves'
      ophthalmopathy treated successfully with glucocorticoids themselves.
AB  - We report a case of acute hepatitis of autoimmune origin which occurred in a 43
      yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves'
      ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no
      previous history of liver disorders or conditions predisposing to GC-associated
      liver damage. After the administration of a 4.7-g cumulative dose of
      methylprednisolone acetate, there was a marked increase of liver enzymes,
      prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes
      increased further, reaching a peak 45 days later, with values 30- to 50-fold
      greater than those prior to therapy, associated with evidence of impaired liver
      function. Liver biopsy showed a marked lymphocytic infiltration, likely
      indicating an autoimmune hepatitis. Based on the assumption that following GC
      induced immune suppression, autoimmune hepatitis might have been precipitated by
      sudden re-activation of the immune system during interpulse periods, we treated
      the patient with im and then oral GC, in order to re-induce immune suppression.
      Within three days from re-institution of GC therapy, there was a marked reduction
      of liver enzymes and amelioration of liver function. Complete normalization was
      achieved two months later, while the patient was still receiving a low
      maintenance dose of oral prednisone.

PMID- 15952416
TI  - Heterogeneous malignancy in toxic thyroid nodules.

PMID- 15952417
TI  - Hemolyzed plasma samples in diabetic ketoacidosis (DKA).

PMID- 15952418
TI  - Already heated specialty hospital debate just got hotter.

PMID- 15952419
TI  - Pay-for-performance tops experts' list to control health care costs.

PMID- 15952420
TI  - Contributing factors and variability of energy expenditure in non-obese, obese,
      and post-obese adolescents.
AB  - Energy expenditure (EE) is a major determinant of energy balance and body
      composition. The objectives of this paper were to review the contributing factors
      of the main components of daily EE (DEE) and the inter-individual variability in
      these components in non-obese (NOb), obese (Ob), and post-obese (POb)
      adolescents. Body composition especially fat-free mass (FFM), is the major
      determinant of the basal metabolic rate which contributes 50-70% of DEE, whereas
      fat mass (FM) is a significant factor only in obese subjects. Physical activity
      is the second main variation factor of DEE, whereas growth, the thermic effect of
      food, and thermoregulation are generally of marginal importance. The energy costs
      and EE associated with various sedentary and physical activities were assessed in
      NOb, Ob and POb subjects both in standardised and in free-living conditions. The
      interindividual variability of DEE is high, even after adjustment for body
      composition, mainly because of great differences in time devoted to the various
      physical activities. DEE and EE associated with sleep and sedentary activities
      are significantly higher in Ob than in NOb, but not after adjustment for FFM. On
      the contrary, EE associated with physical activities is not significantly
      different between Ob and NOb adolescents, but 61% lower in Ob subjects after
      adjustment for body composition. Multidisciplinary weight-reduction programmes
      including moderate energy restriction and physical training result in great FM
      loss, maintenance of FFM, improvement of physical capacities, but reductions in
      organ and tissue metabolic rate and in EE associated with the various sedentary
      and physical activities, which may favour body weight regain in the less active
      POb subjects.

PMID- 15952421
TI  - Relationship between MT1 melatonin receptor gene polymorphism and seasonal
      physiological responses in Ile-de-France ewes.
AB  - The gene encoding the MT1 melatonin receptor in sheep has a restriction fragment
      length polymorphism (RFLP) site to the MnlI enzyme whose incidence is associated
      to the expression of seasonality in several breeds. The aim of this study was to
      examine the relationship between this genetic marker and the physiological
      effects of MT1 receptor gene polymorphism on several seasonal functions in Ile-de
      France ewes. The study was performed using 12 pairs of half-sib adult Ile-de
      France ewes. Within each pair, ewes were selected on the basis of their genotype
      at the MnlI RFLP site: group +/+ and -/- (presence and absence of MnlI
      restriction site, respectively). No difference in the dates of the beginning, the
      end or the length of the breeding season was observed between groups during the
      two-year study. The seasonal changes in prolactin secretion were not different
      between groups. Similarly, wool growth rate and primary follicle activity,
      measured for one year, varied with the time of the year in the same way in the
      two groups. Our study therefore failed to show any relationship between MT1
      polymorphism and reproductive seasonality in Ile-de-France ewes. This suggests
      that the influence of this polymorphism on the regulation of seasonal function is
      dependent upon the breed and/or environmental conditions. The MT1 polymorphism
      can explain only a small part of the genetic variability of seasonal functions
      and the implication of other genes must be investigated.

PMID- 15952423
TI  - Is tryptophan catabolism increased under indoleamine 2,3 dioxygenase activity
      during chronic lung inflammation in pigs?
AB  - In a preliminary study we observed that piglets suffering from chronic lung
      inflammation induced by an intravenous injection of complete Freund adjuvant
      showed a marked decrease in plasma tryptophan (Trp) concentration suggesting
      increased Trp utilisation. During the inflammatory process, a cytokine-induced
      enzyme called indoleamine 2,3-dioxygenase (IDO) has been shown to catabolise Trp
      into kynurenine (Kyn). Yet, during inflammation, increased Trp catabolism may
      decrease Trp availability for other functions such as growth. This metabolic
      pathway has never been studied in pigs. So, the objectives of this study were to
      measure IDO activity in pigs and to determine if the decrease in plasma Trp
      concentrations previously observed in piglets suffering from chronic lung
      inflammation could be explained by the induction of IDO activity. In order to do
      so, we compared IDO activity measured in the tracheo-bronchial lymph nodes and in
      the lungs of 7 piglets, injected with complete Freund adjuvant (CFA), to 7 pair
      fed littermate healthy controls. Blood samples were taken at 0, 2, 5, 7 and 10
      days following CFA injection in order to measure plasma Trp, Kyn and haptoglobin
      concentrations. Indoleamine 2,3-dioygenase activity in the tracheo-bronchial
      lymph nodes (P < 0.05), in the lungs (P < 0.07) and plasma haptoglobin (P < 0.01)
      were higher in pigs with lung inflammation than in the controls. Plasma Trp and
      Kyn were not significantly affected by CFA injection. Our data showed that IDO is
      activated under chronic lung inflammation in pigs. The impact of IDO activation
      on plasma Trp concentration and its availability is discussed according to the
      amount of Trp provided by the diet.

PMID- 15952422
TI  - Effect of long term feeding of ammoniated wheat straw treated with or without HCl
      on blood biochemical parameters in growing male buffalo (Bubalus bubalis) calves.
AB  - Twenty-four growing male buffalo calves (one year of age; 88.54 +/- 3.81 kg
      average body weight) were divided into three comparable groups (I, II and III) on
      the basis of their body weight (BW) in a completely randomised design to study
      the effect of long term feeding of ammoniated wheat straw (AWS) and hydrochloric
      acid treated ammoniated wheat straw (HCl-AWS) on blood biochemical changes. The
      animals were offered a concentrate mixture (CM) along with wheat straw (WS),
      ammoniated wheat straw (AWS) (4% urea at a 50% moisture level) and hydrochloric
      acid treated ammoniated wheat straw (HCI-AWS) (4% urea at a 50% moisture level
      and HCI added to trap 30% of NH3 evolved) in groups I, II and III, respectively
      for an average daily gain (ADG) of 500 g. All the diets were made iso-nitrogenous
      by preparing three types of concentrate mixtures of different CP levels. The
      blood was collected from the jugular vein randomly from three animals of each
      group initially after 8 months post feeding and subsequently after two months
      interval up to 14 months of experimental feeding. Due to urea ammoniation, the CP
      content of WS increased from 3.66 to 8.51 and was further increased to 11.35 due
      to the addition of HCl during urea-ammoniation of wheat straw. The cumulative
      period mean plasma glucose values (mg %), in group II (53.13) were significantly
      (P < 0.001) higher than those in groups I (48.44) and III (50.60). The cumulative
      period mean values of serum albumin and globulin (g %) were not significantly
      different and were comparable among the groups I (3.33 and 3.06), II (3.53 and
      2.97) and III (3.49 and 2.94). The cumulative period mean values of serum
      albumin: globulin ratio and total protein values were not significantly different
      among the different groups. Serum urea and creatinine values were significantly
      (P < 0.001) higher in group III (58.66 and 2.24) as compared to groups I and II.
      The cumulative period mean values of serum alkaline phosphatase (ALP) (KA units)
      did not differ significantly, but serum glutamate pyruvate transaminase (SGPT)
      and glutamate oxaloacetate transaminase (SGOT) values (units x mL(-1) were
      significantly (P < 0.001) higher in groups II and III than in group I. The
      cumulative period mean values of T3 (ng x mL(-1)) did not differ significantly
      among the groups, but T4 values were significantly (P < 0.001) higher in group
      III (22.74) than in groups 1 (21.41) and II (20.89), respectively. Since the mean
      values of all the blood parameters were within the normal range, it may be
      concluded that feeding of ammoniated wheat straw treated with and without HCl to
      growing male buffalo calves for fourteen months has no adverse effect on the
      blood biochemical parameters.

PMID- 15952425
TI  - In situ net mineralization rates in a heterogeneous mixed deciduous forest
      receiving elevated n deposition.
AB  - In situ net mineralization was studied at 6 locations (E, Eb, Ec, F1, F2, F3) of
      a heterogeneous mixed deciduous forest ("De Gulkeputten") with oak (Quercus robur
      L., Quercus rubra) and birch (Betula pendula) as dominant species. Net nitrogen
      mineralization was determined by means of a sequential in situ incubation
      experiment using intact soil cores. For all incubations, the net mineralization
      rates of the organic (F+H) layer varied between -0.4 and 2.0 g N m(-2) month(-1),
      while the net nitrification rates varied between -0.6 and 0.7 g NO3- -N m(-2)
      month(-1). The net mineralization and nitrification rates of the mineral (0-30
      cm) layer ranged from 4.5 g N m(-2) month(-1)to 8.8 g N m(-2) month(-1)and from 
      1.0 to 4.9 g NO3- -N m(-2) month(-1) respectively. In general, net mineralization
      rates increased from August 1998 to October 1998. Net mineralization rates were
      positively correlated with the gravimetrical moisture content and mineralization
      and nitrification rates were mutually positively correlated.

PMID- 15952424
TI  - Probiotic removal of herbicides with endocrine disrupting potential from aqueous
      matrices.
AB  - Water dosed with 50 mg/L of 2,4-D and atrazine was treated to remove the
      herbicides which both are reported to have endocrine disrupting potential. Both
      chemicals could be removed effectively with activated carbon. Yet, traces of
      endocrine disrupter remained in the water and are able to enter the food chain.
      The further biological elimination of these compounds was investigated. Milk
      alone did not decrease the amount of chemicals present in the aqueous
      supernatant. Yet, the probiotic products Bifidus yoghurt (GB), Actimel (Danone)
      and Yakult (Yakult Honsha) appeared to bind a substantial amount of the endocrine
      disrupting chemicals to the particulate fraction and thus render them potentially
      less bio-available in the aqueous phase.

PMID- 15952426
TI  - Seed vigour in Iranian wheat seeds exposed to cold condition.
AB  - Cold stress occurring in the seedbed of winter wheat at the end of autumn results
      in reduced emergence, even of undeteriorated seed lots (which have not been
      subjected to a long period of storage and have not been kept in bad storage
      conditions). The purpose of the present study was to determine the ability of
      different wheat cultivars at emerging at low field temperatures and the
      usefulness of a number of laboratory tests in predicting relative emergence of
      undeteriorated seed lots of different wheat cultivars. Due to genotype
      variability there were different categories of vigour tested through field and
      laboratory tests. There were no significant correlations between laboratory tests
      and field emergence. Our results suggest that conventional vigour tests like
      standard germination and accelerated ageing do not have enough capacity for
      identifying genotype differences when emerging in cold conditions.

PMID- 15952427
TI  - Somatic embryogenesis from flower explants of cocoa (Theobroma cacao L.).
AB  - Two types of flower explants, staminoides and petals, were used for in vitro
      induction of somatic embryos in cocoa. After 14 days in culture, we observed
      globular structures and callus formation on both types of explants. However, the
      better results were obtained on staminoides: 98.3% formed callus and 86.2%
      somatic embryos on Murashige and Skoog (1962) medium supplemented with sucrose,
      coconut water, 2,4-D, kinetin and agar.

PMID- 15952428
TI  - Ley--arable rotation versus permanent arable land and permanent grassland:
      productivity and N-use.

PMID- 15952429
TI  - Impact of land-use on macroinvertebrate communities in the Zwalm river basin.
AB  - For determining the impact of land-use on the aquatic ecosystem in a river basin,
      a Geographic Information System (GIS) has been used to integrate the main impact
      factors at different scales. The headwaters and streams of the Zwalm River basin
      (Flanders, Belgium), which is part of the Scheldt river basin, were selected as
      study site. A river ecological database was developed based on physical-chemical
      and biological monitoring. The research focussed on three zones within this Zwalm
      River basin, each characterized by different land-uses and by consequence
      different types of pollution, mainly of diffuse origin. The impact was measured
      by means of the biological diversity, the Belgian Biotic Index and a key
      macroinvertebrate taxon. For measuring, assessing and managing the impact of land
      use on biological communities, an integrated and multidisciplinary approach will
      be necessary.

PMID- 15952430
TI  - Development of short and long-term management options for bergelenput to avoid
      fish kills caused by algal blooms.
AB  - Numerous stagnant waters in Flanders are characterized by high nutrient
      concentrations, leading to severe algal blooms and under critical conditions to
      fish mortality. In this context, a eutrophicated pond was analysed
      hydrobiologically during one month in order to develop a management plan for the
      coming years to restore its ecological stability. Bergelenput (Wevelgem), a
      former sand pit, is now a nature reserve, currently also used for recreational
      fishing. During the last decade, incidental fish kills have occurred. The main
      cause is thought to be nutrient enrichment, enhancing algal blooms. The most
      probable source of these nutrients is fertiliser runoff from the surrounding
      fields characterised by intensive agricultural activities. Two possible causes of
      these fish kills, both associated with algal blooms, were considered during this
      preliminary study. The first was oxygen depletion of the water caused by algal
      respiration during the night. The second was related to the presence of
      Microcystis aeruginosa, a cyanobacterium known to be toxic sometimes and hence
      responsible for fish kills. Short-term and long-term management options are being
      developed within the context of this research to rehabilitate the ecosystem.

PMID- 15952431
TI  - Development of river ecosystem models for Flemish watercourses: case studies in
      the Zwalm river basin.
AB  - Only recently, modelling has been accepted as an interesting and powerful tool to
      support river quality assessment and management. The 'River Invertebrate
      Prediction and Classification System' (RIVPACS), based on statistical modelling,
      was one of the first and best known systems in this context. RIVPACS was
      developed to classify macroinvertebrate community types and to predict the fauna
      expected to occur in different types of watercourses, based on a small number of
      environmental variables. The prediction is essentially a static 'target' of the
      fauna to be expected at a site with stated environmental features, in the absence
      of environmental stress. Therefore this system is rather limited to apply in
      river assessment and management. Models that offer a prediction of faunal
      responses to changes in environmental features (e.g. changes in discharge regime,
      dissolved oxygen level, ...) would be of considerable value for river management.
      In this context, models based on classification trees, artificial neural networks
      and fuzzy logic were developed and applied to predict macro-invertebrate
      communities in the Zwalm river basin located in Flanders, Belgium. Structural
      characteristics (meandering, substrate type, flow velocity, ...) and physical
      chemical variables (dissolved oxygen, pH, ...) were used as inputs to predict the
      presence or absence of macroinvertebrate taxa in the headwaters and brooks of the
      Zwalm river basin. In total, data from 60 measurement sites were available.
      Reliability and particular strengths and weaknesses of these techniques were
      compared and evaluated. Classification trees performed in general well to predict
      the absence or presence of the different macroinvertebrate taxa and allowed also
      to deduct general relations from the dataset. Models based on artificial neural
      networks (ANNS) were also good in predicting the macroinvertebrate communities at
      the different sites. Sensitivity analyses related to ANNs allowed to study the
      impact of the input variables on the presence or absence of macroinvertebrate
      taxa and to determine the major variables that affect the ecosystem quality and
      should be taken under direct consideration in the management of river basins.
      Performance of the fuzzy logic models was significantly related to the methods
      that were used to set up the membership functions and the reliability of the
      information that was available. Fuzzy logic did not perform as well as the other
      two techniques with regard to short term predictions. Fuzzy logic appeared to be
      better and more robust for long term predictions, because of the easy and
      pragmatic integration of general expert knowledge and data derived rules in the
      transparent inference engine. The overall conclusion of our study is that all
      three techniques, classification trees, artificial neural networks and fuzzy
      logic appeared to be reliable to predict macroinvertebrate communities in
      polluted streams.

PMID- 15952432
TI  - Case report: Urticaria following intentional ingestion of cicadas.

PMID- 15952433
TI  - Antibiotic use for streptococcal pharyngitis groups C and G.

PMID- 15952434
TI  - The vitamin E saga: lessons in patient-oriented evidence.

PMID- 15952435
TI  - Improving adherence to treatment for hypertension.

PMID- 15952436
TI  - Treating GER in children younger than two years.

PMID- 15952437
TI  - Traveler's diarrhea.
AB  - Acute diarrhea affects millions of persons who travel to developing countries
      each year. Food and water contaminated with fecal matter are the main sources of
      infection. Bacteria such as enterotoxigenic Escherichia coli, enteroaggregative
      E. coli, Campylobacter, Salmonella, and Shigella are common causes of traveler's
      diarrhea. Parasites and viruses are less common etiologies. Travel destination is
      the most significant risk factor for traveler's diarrhea. The efficacy of
      pretravel counseling and dietary precautions in reducing the incidence of
      diarrhea is unproven. Empiric treatment of traveler's diarrhea with antibiotics
      and loperamide is effective and often limits symptoms to one day. Rifaximin, a
      recently approved antibiotic, can be used for the treatment of traveler's
      diarrhea in regions where noninvasive E. coli is the predominant pathogen. In
      areas where invasive organisms such as Campylobacter and Shigella are common,
      fluoroquinolones remain the drug of choice. Azithromycin is recommended in areas
      with quinolone-resistant Campylobacter and for the treatment of children and
      pregnant women.

PMID- 15952438
TI  - Information from your family doctor. Traveler's diarrhea: what you should know.

PMID- 15952439
TI  - Treatment of edema.
AB  - Edema is the result of an imbalance in the filtration system between the
      capillary and interstitial spaces. The kidneys play a key role in regulating
      extracellular fluid volume by adjusting sodium and water excretion. Major causes
      of edema include venous obstruction, increased capillary permeability, and
      increased plasma volume secondary to sodium and water retention. A systematic
      approach is warranted to determine the underlying diagnosis. Treatment includes
      sodium restriction, diuretic use, and appropriate management of the underlying
      disorder. Leg elevation may be helpful in some patients. Loop diuretics often are
      used alone or in combination. In patients with New York Heart Association class
      III and IV congestive heart failure, spironolactone has been found to reduce
      morbidity and mortality rates. In patients with cirrhosis, ascites is treated
      with paracentesis and spironolactone. Dihydropyridine-induced edema can be
      treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor
      blocker. Lymphedema occurs when a protein-rich fluid accumulates in the
      interstitium. Compression garments and range-of-motion exercises may be helpful
      in patients with this condition.

PMID- 15952440
TI  - Information from your family doctor. What you should know about edema.

PMID- 15952441
TI  - Evaluation and prevention of diabetic neuropathy.
AB  - Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent
      of patients with diabetes. It is a late finding in type 1 diabetes but can be an
      early finding in type 2 diabetes. The primary types of diabetic neuropathy are
      sensorimotor and autonomic. Patients may present with only one type of diabetic
      neuropathy or may develop combinations of neuropathies (e.g., distal symmetric
      polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the
      most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor
      deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor
      instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual
      dysfunction. Strict glycemic control and good daily foot care are key to
      preventing complications of diabetic neuropathy.

PMID- 15952442
TI  - Information from your family doctor. Diabetic neuropathy.

PMID- 15952443
TI  - Management of heatstroke and heat exhaustion.
AB  - Heat exhaustion and heatstroke are part of a continuum of heat-related illness.
      Both are common and preventable conditions affecting diverse patients. Recent
      research has identified a cascade of inflammatory pathologic events that begins
      with mild heat exhaustion and, if uninterrupted, can lead eventually to
      multiorgan failure and death. Heat exhaustion is characterized by nonspecific
      symptoms such as malaise, headache, and nausea. Treatment involves monitoring the
      patient in a cool, shady environment and ensuring adequate hydration. Untreated
      heat exhaustion can progress to heatstroke, a much more serious illness involving
      central nervous system dysfunction such as delirium and coma. Other systemic
      effects, including rhabdomyolysis, hepatic failure, arrhythmias, disseminated
      intravascular coagulation, and even death, are not uncommon. Prompt recognition
      and immediate cooling through evaporation or full-body ice-water immersion are
      crucial. Physicians also must monitor electrolyte abnormalities, be alert to
      signs of renal or hepatic failure, and replace fluids in patients with
      heatstroke. Most experts believe that physicians and public health officials
      should focus greater attention on prevention. Programs involving identification
      of vulnerable individuals, dissemination of information about dangerous heat
      waves, and use of heat shelters may help prevent heat-related illness. These
      preventive measures, when paired with astute recognition of the early signs of
      heat-related illness, can allow physicians in the ambulatory setting to avert
      much of the morbidity and mortality associated with heat exhaustion and
      heatstroke.

PMID- 15952444
TI  - Information from your family doctor. Heat exhaustion and heatstroke: what you
      should know.

PMID- 15952445
TI  - Screening for abdominal aortic aneurism.

PMID- 15952446
TI  - Treatment of calf deep venous thrombosis.

PMID- 15952447
TI  - An elderly woman with a non-healing ulcer. Marjolin's ulcer.

PMID- 15952448
TI  - Effect of alternative on-site wastewater treatment on the viability and
      culturability of Salmonella choleraesuis.
AB  - The objective of this study was to determine how alternative on-site wastewater
      treatment systems (i.e. subsurface flow constructed wetlands, intermittent sand
      filters and intermittent peat filters) affect the viability and culturability of
      Salmonella choleraesuis (serotype typhimurium, ATCC 23567). Influent was a high
      strength septic tank effluent (BOD5 240-344 mgL(-1), TN approximately 100 mgL(
      1), TP approximately 15 mgL(-1)) at the Natural Resources Research Institute's
      (NRRI) alternative treatment system test facility in northern Minnesota.
      Treatment systems were inoculated with cultures of S. choleraesuis for 5-7
      consecutive days in summer and winter during 1998-99. After the seeding, outflow
      samples were taken until Salmonella counts were sustained at background levels.
      In addition to culture-based enumeration, S. choleraesuis abundances were also
      measured using fluorescent in situ hybridization (FISH) alone and in combination
      with the direct viable count method (DVC) to determine if plate counts
      underestimated total and viable Salmonella abundances and if the Salmonella cell
      viability changed after passing through the treatment systems. In most cases,
      total and viable cell abundances in treatment system effluents were several
      orders of magnitude higher than cultured cell abundances. Our results indicate
      that the culture-based method underestimated viable concentrations of the model
      pathogen, S. choleraesuis. Salmonella cell viability decreased in effluents
      during the summer but increased during the winter. Using a culture-based
      enumeration method alone to determine removal efficiencies of bacterial
      indicators and pathogens for wastewater treatment systems may result in
      artificially high estimates of effective treatment.

PMID- 15952449
TI  - Development and test for long-term stability of a synthetic standard for a
      quantitative Cryptosporidium parvum LightCycler PCR assay.
AB  - A recently described quantitative rapid cycle real time PCR (LightCycler) assay
      detects Cryptosporidium parvum after in vitro excystation, which is a surrogate
      marker for the viability of the organisms. In the original assay the
      quantification standard is a dilution series of C. parvum oocysts with a
      microscopically determined excystation rate. The need to keep suspensions of
      viable oocysts in stock and to continuously monitor their excystation rate,
      however, renders the assay impracticable for routine application. A synthetic
      standard was developed to replace the in vivo standard and was calibrated using
      oocysts with known excystation rates. The standard consists of a 486 bp DNA
      segment ranging from 229 bp upstream to 79 bp downstream of the actual PCR target
      site. Aliquots of the standard were frozen and stored at -20 degrees C and at -70
      degrees C or lyophilised and stored at room temperature in the dark. For a period
      of one year samples preserved with each of the three methods were restored every
      four or five weeks. They were amplified in the LightCycler and the crossing
      points (CP) were monitored. No significant trend in the raw CP values could be
      observed for any of the three storage methods. However, when the methods were
      compared to each other by calculating the CP ratios (-20 degrees C/-70 degrees C;
      -20 degrees C/lyophilised; -70 degrees C/lyophilised) at the 10 monitoring dates,
      the CP ratios -20 degrees C/-70 degrees C and -20 degrees C/lyophilised showed a
      highly significant positive trend (p < 0.0001) while the CP ratio -70 degrees
      C/lyophilised did not differ from the null hypothesis (p = 0.53). It can be
      concluded that the latter two preservation methods are both appropriate, while
      storage at -20 degrees C is less advisable. Calculations based on the molecular
      weight of the standard and on the assumption of an average yield of three
      sporozoites per oocyst led to the conclusion that the target sequence is probably
      located on a double copy gene.

PMID- 15952450
TI  - Home water treatment by direct filtration with natural coagulant.
AB  - Seeds of the plant species Strychnos potatorum and Moringa oleifera contain
      natural polyelectrolytes which can be used as coagulants to clarify turbid
      waters. In laboratory tests, direct filtration of a turbid surface water
      (turbidity 15-25 NTU, heterotrophic bacteria 280-500 cfu ml(-1), and fecal
      coliforms 280-500 MPN 100 ml(-1)), with seeds of S. potatorum or M. oleifera as
      coagulant, produced a substantial improvement in its aesthetic and
      microbiological quality (turbidity 0.3-1.5 NTU, heterotrophic bacteria 5-20 cfu
      ml(-1) and fecal coliforms 5-10 MPN 100 ml(-1)). The method appears suitable for
      home water treatment in rural areas of developing countries. These natural
      coagulants produce a 'low risk' water; however, additional disinfection or
      boiling should be practised during localised outbreaks/epidemics of enteric
      infections.

PMID- 15952451
TI  - Effective water supply surveillance in urban areas of developing countries.
AB  - Water supply surveillance generates data on the safety and adequacy of drinking
      water supply in order to contribute to the protection of human health. Most
      current models of water supply surveillance for urban areas come from developed
      countries and have significant shortcomings if directly applied elsewhere. There
      are differences not only in socio-economic conditions but also in the nature of
      water supply services, which often comprise a complex mixture of formal and
      informal services for both the 'served' and 'unserved'. The development of
      approaches to water supply surveillance that allow targeting of activities on
      priority groups is assessed based on case studies from Peru and Uganda. The
      development of a zoning approach that incorporates indices for vulnerability is
      shown to be a useful tool to assist surveillance in targeting data collection.
      Zoning also assists in targeting subsequent interventions into communities and
      strategies where public health gains are likely to be greatest. Two approaches to
      urban zoning are presented from Peru and Uganda, both of which are effective.

PMID- 15952452
TI  - Ferrates (iron(VI) and iron(V)): environmentally friendly oxidants and
      disinfectants.
AB  - Iron(VI) and iron(v), known as ferrates, are powerful oxidants and their
      reactions with pollutants are typically fast with the formation of non-toxic by
      products. Oxidations performed by Fe(VI) and Fe(V) show pH dependence; faster
      rates are observed at lower pH. Fe(VI) shows excellent disinfectant properties
      and can inactivate a wide variety of microorganisms at low Fe(VI) doses. Fe(VI)
      also possesses efficient coagulation properties and enhanced coagulation can also
      be achieved using Fe(VI) as a preoxidant. The reactivity of Fe(V) with pollutants
      is approximately 3-5 orders of magnitude faster than that of Fe(VI). Fe(V) can
      thus be used to oxidize pollutants and inactivate microorganisms that have
      resistance to Fe(VI). The final product of Fe(VI) and Fe(V) reduction is Fe(III),
      a non-toxic compound. Moreover, treatments by Fe(VI) do not give any
      mutagenic/carcinogenic by-products, which make ferrates environmentally friendly
      ions. This paper reviews the potential role of iron(VI) and iron(V) as oxidants
      and disinfectants in water and wastewater treatment processes. Examples are given
      to demonstrate the multifunctional properties of ferrates to purify water and
      wastewater.

PMID- 15952453
TI  - Occurrence and correlations between coliphages and anthropogenic viruses in the
      Massachusetts Bay using enrichment and ICC-nPCR.
AB  - We evaluated a two-step enrichment procedure to detect coliphages and an
      integrated cell culture-nested polymerase chain reaction (ICC-nPCR) to detect
      human astrovirus, enteroviruses, rotavirus and adenovirus type 40 and 41 in
      marine water samples collected by the Massachusetts Water Resource Authority
      (MWRA). MWRA has been monitoring its receiving waters for coliphages,
      anthropogenic viruses and indicator bacteria in order to evaluate the impact of
      Boston's Deer Island Sewage Treatment Plant discharge. Coliphages and enteric
      viruses were originally assayed using single agar overlay and most probable
      number cell culture (MPN) methods, respectively. Reanalysis of these samples for
      enteric viruses by ICC-nPCR demonstrated that 46% were positive for at least one
      virus compared with 23% with the MPN method. Use of the enrichment method showed
      a 47% increase in the detection of male specific and somatic coliphages compared
      with the single agar overlay method. Correlations between the presence of
      coliphages, enteric viruses and indicator bacteria were based on proximity to the
      treatment plant discharge, seasonal variations and site levels. The presence of
      enteric viruses was significantly correlated to coliphages but not to indicator
      bacteria. Preliminary comparative results demonstrate that effective and
      efficient monitoring of anthropogenic contamination can be achieved using these
      more sensitive and specific techniques.

PMID- 15952454
TI  - Aspects of health-related microbiology of the Subin, an urban river in Kumasi,
      Ghana.
AB  - The aim of this study was to assess the influence of urban waste, sewage and
      other human centred activities on the microbiological quality of the river Subin,
      which flows through the metropolis of Kumasi, Ghana, and serves as drinking water
      for communities downstream. Three sites, Racecourse, Asafo and Asago, on the
      Subin were monitored over a year for total coliforms, faecal coliforms,
      enterococci and biochemical oxygen demand. Bacterial indicator numbers (geometric
      mean 100 ml(-1)) varied from 1.61 x 10(9) to 4.06 x 10(13) for total coliforms,
      9.75 x 10(8) to 8.98 x 10(12) for faecal coliforms and 1.01 x 10(2) to 6.57 x
      10(6) for enterococci. There was a consistent increase in bacterial loading as
      the river flows from the source (Racecourse) through Kumasi. Bacterial numbers
      were significantly (p < or = 0.05) higher during the rainy season compared with
      the dry (harmattan) season. The biochemical oxygen demand ranged from 8 mg l(-1)
      at the source of the river to 419 mg l(-1) at Asago; none of the sites achieved
      internationally accepted standards for water quality. The River Subin becomes
      grossly polluted as it flows through Kumasi and at Asago, a rural community
      downstream of Kumasi that abstracts water from the river for drinking, this
      probably contributes to the observed high levels of diarrhoeal disease.

PMID- 15952455
TI  - Serological responses to Cryptosporidium antigens among women using riverbank
      filtered water, conventionally filtered surface water and groundwater in Hungary.
AB  - We compared serological responses to Cryptosporidium parvum antigens using
      surplus sera from females undergoing routine screening for pregnancy from three
      counties in Hungary where bank-filtered surface water, conventionally filtered
      and disinfected surface water, and groundwater from either a karst or confined
      aquifer are commonly used for drinking water. The primary purpose was to
      determine whether the prevalence and intensity of serological responses,
      indicators of prior Cryptosporidium infection were similar for these populations.
      Women using groundwater from a confined aquifer had significantly lower mean
      serological responses for both the 15/17-kDa and 27-kDa (p < 0.0001) antigen
      groups than women using conventionally filtered and disinfected surface water or
      karst well water. This is suggestive of less frequent infections. Women using
      bank-filtered water also had lower mean responses for both antigen groups. Among
      women using bank-filtered water, the mean intensity of response for both antigen
      groups was almost one-third of the mean response observed for women using
      conventionally filtered and disinfected surface water. These findings suggest
      that riverbank filtration may be an effective alternative to conventional
      treatment for reducing Cryptosporidium exposures and infection from surface
      drinking water sources.

PMID- 15952456
TI  - Isolation and identification of freshwater bacteria antagonistic to Giardia
      intestinalis cysts.
AB  - We have isolated three freshwater bacterial strains that demonstrate the ability
      to degrade Giardia intestinalis cysts. These strains have been identified by 16S
      rRNA sequencing and phylogenetic analysis as belonging to the Flavobacterium
      columnare clade of the Cytophaga-Flavobacterium group. While the cyst degradation
      mechanism is unclear, two different effects on the cysts were observed: non
      viability and lysis. Cysts exposed to bacterial strains BR1 and SC1 were
      generally non-viable, but remained structurally intact. In contrast, cysts
      exposed to strain SR1 were clearly lysed. Increases in bacterial densities with a
      concomitant decrease in cyst viability suggest that these bacterial strains are
      capable of using the cysts to enhance their growth. We propose that the presence
      of bacterial strains such as SR1, BR1 and SC1 may play a role in reducing the
      viability of G. intestinalis cysts in natural waters.

PMID- 15952457
TI  - Patient safety: rejecting the status quo.

PMID- 15952458
TI  - Improving diabetes care among low-income North Carolinians: Project IDEAL.
AB  - OBJECTIVES: Many barriers exist in implementing evidence-based guidelines for
      diabetes care, particularlyfor low-income patients. To address this, the North
      Carolina Project IDEAL (Improving Diabetes Education, Access to Care, and Living)
      Diabetes Initiative was created STUDY DESIGN/SETTING: Fourteen programs
      representing different types of agencies and intervention strategies across the
      state participated in the initiative. DATA COLLECTION: Separate random samples of
      medical charts of participating patients were reviewed at baseline (n=429) and
      three-year follow-up (n=656) to assess changes in six process (assessment of
      hemoglobin A1c, cholesterol blood pressure, and urinary protein; conduction of
      foot and retina examination) and three outcome (glycemia, blood pressure, and
      lipid control) measures. Four national guidelines (DQIP, HEDIS, NCEP and ADA)
      were used as benchmarks. RESULTS: Large increases were observed for some measures
      (hemoglobin A1c control and testing, LDL-cholesterol testing), while modest
      increases were observed for others (dilated eye exam, blood pressure testing, and
      control). CONCLUSIONS/RELEVANCE: Project IDEAL was successful in improving access
      to high-quality diabetes care for low-income patients. Additional effort is
      needed to address specific areas of concern, particularly retinopathy screening.

PMID- 15952459
TI  - Accommodating a new medical profession: the history of physician assistant
      regulatory legislation in North Carolina.
AB  - The first physician assistant program in the United States was at Duke University
      Medical Center. This program served as a model for other institutions to begin
      similar educational programs, and the profession has quickly become a major
      source of medical services throughout the country. Less well-known is the role of
      Duke University and North Carolina in the development of a unique regulatory
      system, which also became a national model. This system has been effective in
      protecting the public and the patient, and has had the flexibility to adapt to
      changing medical practice and changing standards. The process by which this
      regulatory system was developed was unique, and its unique characteristics are
      felt to have been a significant factor in its success. Duplication of these
      characteristics is recommended for those who wish to incorporate new medical
      occupations into the larger medical community.

PMID- 15952460
TI  - The North Carolina Healthcare Safety Net, 2005: fragments of a lifeline serving
      the uninsured.
AB  - North Carolina is in the midst of a quiet, but growing healthcare crisis. The
      number of uninsured residents is rising at an alarming rate--and a faster rate
      than in most other states. Almost one of every five (20%) non-elderly North
      Carolinians have no health insurance, which means a sizeable portion of our
      population has unmet healthcare needs. As healthcare costs continue to increase,
      North Carolina is likely to continue seeing increased numbers of uninsured. Until
      we can dramatically reduce the volume of the uninsured, there will be a
      continuing and growing need for governmental, private sector, and voluntary
      healthcare providers to serve this population. In this issue of the Journal, we
      have attempted to draw attention to the volume and variety of services, programs,
      and organizations involved in meeting this important healthcare need among our
      state's most vulnerable populations. The organizations involved in rendering
      these services, and the private physicians and other healthcare professionals who
      give of their time and talents to meet these needs, are stretched to their limits
      in most communities. The Task Force has recommended several concrete steps that
      would shore up safety net organizations' and individual providers'
      capacity/ability to meet these needs. Some of these steps will require rather
      straightforward changes in regulations and laws governing the provision of
      healthcare services. Others will require appropriation of funds to augment the
      public, private, and voluntary support now given through these safety net
      provider organizations in support of their efforts to serve the uninsured. While
      some effort needs to be made to bring these issues to the attention of the
      state's Congressional delegation in Washington, DC, many of these problems should
      not have to wait for federal action. The needs are great, and the demands for
      service are increasing among those organizations and professionals who have
      assumed these responsibilities in counties and communities across our state. For
      those with healthcare insurance, these problems and their administrative
      complexities may seem of remote interest and concern. But, for the people who
      depend on the safety net services, these problems can mean the difference between
      health, work, and opportunity, or between disease, disability, or death. There is
      a genuine collective benefit to meeting the healthcare needs of the uninsured,
      for the health and wellbeing of a fifth of our state's population affects the
      health of all of us. Depending on a stop-gap, safety net to maintain the health
      of such a large segment of our population is a societal risk we all must
      confront. Failure of any part of the healthcare safety net could be detrimental
      to the stability of the larger healthcare system on which we all depend.

PMID- 15952461
TI  - Federally qualified health centers: providing healthcare to North Carolina's
      communities in medical need.

PMID- 15952462
TI  - North Carolina state government and the healthcare safety net: building the
      nation's most extensive network of rural health centers.

PMID- 15952463
TI  - Free clinics in North Carolina: a network of compassion, volunteerism, and
      quality care for those without healthcare options.

PMID- 15952464
TI  - Local physicians caring for their communities: an innovative model to meeting the
      needs of the uninsured.

PMID- 15952465
TI  - The hospital emergency department: an anchor for the community's healthcare
      safety net.

PMID- 15952466
TI  - Our healthcare system is failing.

PMID- 15952467
TI  - Public health departments: the under-funded provider of last resort.

PMID- 15952468
TI  - Pharmaceutical companies meet the needs of the poor and uninsured: an important
      element in the healthcare safety net.

PMID- 15952469
TI  - Free prescriptions? Yes,there is a way!

PMID- 15952470
TI  - Integrating multiple service providers in service to the poor and uninsured: the
      critical conditions for effective collaboration.

PMID- 15952471
TI  - Rising student health needs require a school safety net.

PMID- 15952472
TI  - AHEC teaching clinics in service to the uninsured.

PMID- 15952473
TI  - Who is at risk of losing safety net healthcare?

PMID- 15952474
TI  - Uninsured and underinsured adults in North Carolina.

PMID- 15952475
TI  - Using failure mode effects analysis to solve clinical system problems... It's
      easier than you think!

PMID- 15952476
TI  - Working together for success.
AB  - Administrators and Directors of Nursing usually believe they are doing the right
      thing when they begin to implement an ergonomic program such as safe resident
      handling. However, as time goes by, and the program fades, they may wonder where
      they went wrong. The commitment, planning, and follow through between
      "management" and "employees" when a safe resident handling/minimal lift program
      is implemented is an essential, but often overlooked, part of an effective
      ergonomic program. The best of programs can fail unless there is an ongoing
      effort by both to insure that the following goals are achieved: (1) safety for
      the caregivers, (2) safety for the residents, and (3) improvement or maintenance
      of mobility of the residents.

PMID- 15952477
TI  - The management of GERD in the LTC environment: a medical director's perspective.

PMID- 15952478
TI  - Late-life schizophrenia. What providers need to know.

PMID- 15952479
TI  - Bedrail entrapment and a paralyzed industry.

PMID- 15952480
TI  - Complementary approaches to hypertension.

PMID- 15952481
TI  - Patients in pain: What they say, and what they really mean.

PMID- 15952482
TI  - Paroxysmal atrial fibrillation: why patients experience different symptoms from
      the same arrhythmia?
AB  - A careful evaluation and interpretation of the symptoms of the patient with
      atrial fibrillation should be the first step in selecting a treatment modality.
      Arrhythmia burden is not equal to symptoms. Some patients will have and continue
      to have symptoms not related to the occurrence of arrhythmias. Recognition of
      these patients is important in the treatment of atrial fibrillation.

PMID- 15952483
TI  - Hepatitis C virus and human immunodeficiency virus coinfection: where do we
      stand?
AB  - Both human immunodeficiency virus (HIV) and hepatitis C (HCV) are globally
      infecting millions of people. Since these viruses are both transmitted through
      blood-blood contact the rate of coinfection is as high as 30% and among i.v. drug
      users in the Western world 70%. In The Netherlands, 8% of HCV-infected patients
      are coinfected with HIV. After the successful introduction of antiretroviral
      therapy (HAART) the survival of patients with HIV has increased considerably.
      Coinfection leads to accelerated progression of liver cirrhosis and liver failure
      but conflicting evidence exists about the effect of HCV on the natural course of
      HIV. Four randomised controlled trials have shown that treatment with pegylated
      interferon plus ribavirin leads to an overall sustained viral response (SVR) rate
      between 27 and 44%. Divided by genotype the SVR is between 14 and 38% in genotype
      1 (and 4) while between 53 and 73% for genotype 2 and 3. These percentages are
      calculated based on an intention-to-treat analysis. Although lower than in HCV
      monoinfected patients this is much higher than achieved with conventional
      interferon. However, coinfected patients with genotypes 2 and 3 also need to be
      treated for 48 weeks in contrast to monoinfected patients. As the number and
      severity of side effects is low, coinfected patients now have a substantially
      better option for treatment.

PMID- 15952484
TI  - Blood glucose awareness training in Dutch type 1 diabetes patients: one-year
      follow-up.
AB  - BACKGROUND: American studies have shown positive effects of Blood Glucose
      Awareness Training (BGAT) on the recognition of hypoglycaemia. We evaluated the
      effects of BGAT among Dutch patients, and compared individual training with
      training in the original group format. METHODS: Fifty-nine type 1 diabetes
      patients participated in BGAT in either a group (n = 37) or an individual (n =
      22) setting. Before and one year after training they performed up to 70
      measurements, two to four a day, at home on a handheld computer. During each
      measurement they estimated their blood glucose (BG), indicated whether they would
      be participating in traffic and raised their BG on the basis of their estimation,
      and then measured their BG. The incidence of severe hypoglycaemia and traffic
      accidents was also assessed. RESULTS: BGAT had positive effects on hypoglycaemic
      awareness, decisions not to drive and to raise the blood glucose during
      hypoglycaemia, severe hypoglycaemic episodes and traffic accidents. The accuracy
      of BG estimations only improved after group training, while after individual
      training patients tended to measure more or more extremely high BG values.
      CONCLUSION: The training improved awareness of hypoglycaemia, and seems worthy of
      implementation in The Netherlands.

PMID- 15952485
TI  - Paroxysmal atrial fibrillation, quality of life and neuroticism.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (AF) is associated with significant
      impairment of quality of life (QoL), which is to a large extent independent of
      objective measures of disease severity. We sought to investigate the potential
      role of neuroticism in the impairment of QoL in patients with paroxysmal AF.
      METHODS: The study group (AF group) comprised 73 patients with paroxysmal AF
      (mean age 55.5 +/- 113.3 years, 50 males). On average, patients had a three-year
      history of one symptomatic paroxysm a week lasting two hours. QoL was assessed
      using the Medical Outcomes Study Short Form (SF-36) and neuroticism was assessed
      using the short-scale Eysenck Personality Questionnaire (EPQ). RESULTS: The
      degree of neuroticism in the AF patient group did not differ from the degree of
      neuroticism in a group of age- and sex-matched controls (mean EPQ score on
      neuroticism 4.1 +/- 3.0 and 3.9 +/- 3.1, respectively; p = NS). Within the AF
      group, multivariate regression analyses showed that QoL in the physical domain
      (SF-36 physical functioning, physical role function, vitality and pain subscales)
      was not related the degree of neuroticism. In contrast, significant inverse
      relations were observed between scores on the mental health and social
      functioning subscales and the degree of neuroticism (beta coefficients p < .05),
      independent of age, sex and symptoms. CONCLUSION: Based on the present study,
      patients with paroxysmal AF appear to have on average a degree of neuroticism
      similar to age- and sex-matched controls. However, the impairment of QoL in these
      patients, in particular regarding social functioning and mental health, seems to
      be related to a relatively high degree of neuroticism, independent of age and
      sex.

PMID- 15952486
TI  - Clinical experience with venlafaxine in the treatment of hot flushes in women
      with a history of breast cancer.
AB  - OBJECTIVE: To obtain practical experience with venlafaxine for hot flushes in
      breast cancer patients and incorporate this in a treatment protocol. METHOD:
      Twenty-two women with a history of breast cancer (mean age 49.2 years, range 35
      65) were referred for consideration of treatment with venlafaxine for hot
      flushes. Patients received extensive information on treatment with venlafaxine
      and were advised to self-monitor the frequency of their hot flushes. RESULTS:
      Eight women did not start venlafaxine because they had no postmenopausal
      complaints, were lost to follow-up, had too low a frequency of hot flushes, or
      refused treatment. Eventually 14 women started venlafaxine. Two of them did not
      tolerate venlafaxine, four reported some effect but stopped because of side
      effects, two women had no effect whatsoever. Six women observed a clear ( > 50%)
      reduction in their hot flush frequency that was maintained at a median follow-up
      of 13 months. CONCLUSION: The group of patients referred for treatment was more
      heterogeneous and more patients dropped out because of side effects than
      expected. Extensive patient education, patient selection and evaluation of the
      treatment effect (by self-monitoring of hot flush frequency) are mandatory to
      avoid useless (continuation of) treatment and to prepare patients for side
      effects. Under these conditions, a substantial minority of patients benefit from
      venlafaxine.

PMID- 15952487
TI  - A patient with abdominal distension.
AB  - A 74-year-old woman was admitted to our hospital because of vomiting and
      abdominal pain. She had been well until 24 hours before admission, when she had
      had her last meal. She had not eaten anything unusual. She developed pain in the
      left lower abdominal quadrant, and difficulties with her bowel movements. An
      enema was given unsuccessfully. There was progressive distension of the abdomen.
      The patient started to vomit gastric and later bilious contents. No history of
      abdominal symptoms or weight loss was reported. She currently takes oral
      antidiabetic agents and an angiotensin II blocker because of hypertension. On
      physical examination she was not in distress and was afebrile, blood pressure
      130/100 mmHg, pulse rate 88 beats/min. On auscultation increased bowel sounds
      with rushes of high-pitched sounds were heard. Her abdomen was distended and a
      large tender mass filling the whole left lower quadrant without signs of
      peritoneal irritation was found. There were no faeces on rectal examination. The
      leucocyte count was 10.2 mmol/L, haemoglobin 7.2 mmol/L, C-reactive protein 36
      mg/l and lactate dehydrogenase 535 U/l. Under suspicion of a mechanical bowel
      obstruction without signs of peritonitis, the patient was treated with a
      nasogastric tube, fasting and enemas on which she improved. An abdominal X-ray in
      bed taken on day two showed no bowel distension (figure 1). After removing the
      nasogastric tube on day two the nausea returned. Abdominal examination was
      unchanged. An abdominal computed tomography (CT) scan after drinking oral
      contrast and intravenous contrast was performed (figure 2).

PMID- 15952488
TI  - Neurological complications following Plasmodium falciparum infection.
AB  - Several neurological complications are associated with severe falciparum malaria.
      Cerebral malaria is one of the most life-threatening complications. A few
      patients may experience a neurological syndrome after complete recovery from
      Plasmodium falciparum infection. In the literature especially the postmalaria
      neurological syndrome (PMNS), acute disseminated encephalomyelitis (ADEM) and
      delayed cerebellar ataxia have been reported. We describe a case of a 53-year-old
      woman who was readmitted after an adequately treated P. falciparum infection with
      word-finding difficulties, confusion and tremor. Peripheral blood smears were
      repeatedly negative for malarial parasites. The clinical features best fitted a
      PMNS. Because of the severity of the syndrome she was treated with high-dose
      prednisone. She recovered completely. The possibility of ADEM is also discussed.
      Aetiology of these syndromes is still unknown, but it could be mediated by an
      immunological mechanism. PMNS or ADEM must be considered when neurological signs
      and symptoms occur after recovery from a P. falciparum infection.

PMID- 15952489
TI  - Treatment of postoperative bleeding after fondaparinux with rFVIIa and tranexamic
      acid.
AB  - Treatment of a haemorrhagic shock after just a single dose of fondaparinux in an
      orthopaedic patient with reduced renal clearance is presented. Since all routine
      haemostatic parameters were nearly normal, single doses of rFVIIa (90 microg/kg)
      and of tranexamic acid (15 mg/kg) were administered to improve thrombin
      generation and reduce fibrinolysis. This case is the first showing the
      effectiveness of combining single doses of rFVIIa and tranexamic acid in
      controlling severe postoperative bleeding after fondaparinux.

PMID- 15952490
TI  - [Surgical treatment of obstructive sleep-apnoea syndrome].
AB  - 5 patients, 4 males aged 41, 32, 52 and 49 years and 1 female aged 57 years,
      suffered from socially unacceptable snoring and hypersomnolence in the daytime.
      They were evaluated for obstructive sleep-apnoea syndrome. After polysomnography
      and sleep endoscopy was performed to establish the severity of the sleep-apnoea
      syndrome and the level(s) of upper airway obstruction, a patient-specific
      treatment was performed. Conservative therapy with continuous positive airway
      pressure (CPAP) was refused by 4 patients, while 1 patient discontinued therapy
      after complaints of nose obstruction. This patient underwent radiofrequency
      thermotherapy (RFTT) of the inferior turbinates. The other patients underwent
      uvulopalatopharyngoplasty (UPPP), RFTT of the soft palate, hyoidthyroidpexia
      (HTP) and 'multilevel' surgery: UPPP, HTP and RFTT of the tongue base,
      respectively. All patients showed improvement after surgery. Although its
      longterm effects are not yet known, surgical treatment is an option for patients
      with obstructive sleep-apnoea syndrome who cannot or will not undergo CPAP.

PMID- 15952491
TI  - [The practice guideline 'Anxiety disorders' (first revision) from the Dutch
      College of General Practitioners; a response from the perspective of general
      practice].
AB  - The recommendations provided by the revised guideline 'Anxiety disorders' are
      well suited to every-day practice. The multidisciplinary approach reflects the
      increasing cooperation between primary and secondary care in the management of
      mental-health problems. The description of the various anxiety disorders and the
      questions that can be asked to elicit the symptoms will facilitate recognition.
      The indications for treatment with medication are clear: a limited number of
      antidepressants should be used. Although it is agreed that patient education is
      an important part of treatment, the guidelines could have described in more
      detail how this should be done. Cognitive-behavioural techniques may be used but
      this requires extra training; its effectiveness when used by general
      practitioners needs further study. This guideline will add to existing knowledge
      and improve the skills of general practitioners in dealing with anxiety.

PMID- 15952492
TI  - [The practice guideline 'Anxiety disorders' (first revision) from the Dutch
      College of General Practitioners; a response from the perspective of psychiatry].
AB  - The revised version of the practice guideline 'Anxiety disorders' from the Dutch
      College of General Practitioners largely agrees with the Dutch interdisciplinary
      guidelines. It was agreed that the interdisciplinary guidelines would function as
      the standard and the professional guidelines would be derived from these.
      Differences concern the need to distinguish anxiety disorders as distinct
      conditions, the need to question about psychiatric disorders in the family, the
      status of tricyclic anti-depressants (TCAs) and selective serontonin re-uptake
      inhibitors (SSRIs), the medicinal possibilities, and the possibility of an one
      offconsultation with a psychologist or psychiatrist.

PMID- 15952493
TI  - [Reporting accidents and (near) mistakes: meaning and possibilities of
      legislation].
AB  - Several proposals have been made to introduce systems for blame-free reporting of
      medical accidents and possible mistakes in Dutch health-care facilities. These
      systems are aimed at improving patient safety. The question whether health-care
      workers who report accidents and mistakes should be protected by legislation has
      been raised. In a number of countries, this kind of legal protection has been
      developed. Most of these laws stipulate that information provided in the context
      of a reporting system may not be used against the reporter in a legal procedure.
      In order to improve the willingness of health-care workers to report, it may be
      worthwhile to introduce this kind of legal protection.

PMID- 15952494
TI  - [The influence of sexual function on the chance of pregnancy].
AB  - There is a complex association between sexual behaviour and (in)fertility. Sexual
      dysfunction can cause a delay in conception, but can also be the result of not
      conceiving. If conception is not achieved, sexual function may become disturbed
      and can deteriorate further as the result of the hospital fertility protocol and
      medical intervention. In terms of fertility, optimal sexual function is important
      because it increases the chance of conception. The greatest chance of conception
      is achieved through sexual intercourse on multiple occasions during the fertile
      period, particularly on days with good quality cervical mucus, with the right
      interval between ejaculations (not too long and not too short), adequate arousal
      of both partners and without the use of artificial lubricants. Time and
      attentiveness are particularly important in the patient-physician contact to be
      able to properly advise couples on these matters.

PMID- 15952495
TI  - [Summary of the practice guideline 'Anxiety disorders' (first revision) from the
      Dutch College of General Practitioners].
AB  - Anxiety disorders are characterised by excessive fears leading to distress or
      social disability. Anxiety disorders are difficult to recognise. General
      practitioners (GPs) should consider the possibility more often, especially in
      patients who make frequent visits with unexplained physical symptoms. The
      cornerstone of treatment is patient education, which can be supported by
      information leaflets provided by the Dutch College of General Practitioners.
      Cognitive behavioural therapy and antidepressants are equally effective therapies
      in most anxiety disorders. The choice should be made in collaboration with the
      patient. Pharmacological treatment is the first choice when a comorbid depression
      is involved. Cognitive behavioural therapy by the GP is optional considering the
      limitations of skills and time in general practice. Tricyclic antidepressants and
      selective serotonin re-uptake inhibitors are equally effective with most anxiety
      disorders. The choice must be made on the basis of side effects, comorbidity, and
      co-medication. Antidepressant therapy should be given for at least 6-12 months.
      The GP's choice oftreatment should lead to improvement within 8-12 weeks.
      Otherwise, consultation of or referral to a specialist in mental health care is
      mandatory.

PMID- 15952496
TI  - [Diagnostic image (239). A male newborn with a skin lesion on a knee].
AB  - Cutis marmorata teleangiectatica congenita was diagnosed in a male neonate.

PMID- 15952497
TI  - [Resistance of gonococci in the Netherlands; results of a survey of medical
      microbiology laboratories].
AB  - OBJECTIVE: To collect information about the incidence ofgonorrhoea and gonococcal
      resistance in the Netherlands. METHOD: A questionnaire was sent to 39 medical
      microbiology laboratories to obtain information on current diagnostics and the
      susceptibility testing method, and on the number of positive results and the
      susceptibility pattern of gonococcal isolates in 2002 and 2003 (up to and
      including November). RESULTS: 32 laboratories participated in this survey. 13
      laboratories used culture alone and 19 laboratories used culture and/or a
      molecular test. Gonorrhoea was diagnosed 2,666 times in 2002 and 2,190 times in
      2003, with an incidence of 33.5 and 27.0 per 100,000 inhabitants, respectively.
      The rate of resistance to beta-lactam antibiotics (penicillin and amoxicillin)
      was 12.2% and 10.7% in 2002 and 2003, respectively, and the rates of resistance
      to tetracycline were 18.5% and 20.6%. An increase in the resistance to quinolones
      was observed from 6.6% in 2002 to 9.5% in 2003. Resistance to cephalosporins was
      low (0.5% in 2002 and 1.2% in 2003). Furthermore, regional differences in
      susceptibility were found within the Netherlands. CONCLUSION: The observed
      gonococcal incidence and resistance form the basis for a gonorrhoea prevention
      and treatment programme in the Netherlands.

PMID- 15952498
TI  - [Obstructive sleep-apnoea syndrome: good results with maxillo-mandibular
      osteotomy after failure of conservative therapy].
AB  - A 36-year-old woman and a 49-year-old man with symptoms of an obstructive sleep
      apnoea syndrome benefited insufficiently from the therapy of choice, i.e.
      treatment with continuous positive airway pressure. Minor surgical procedures to
      improve the upper airways did not have the desired effect. Subsequently, maxillo
      mandibular osteotomy was performed. Thereafter, both the daytime somnolence and
      the snoring during sleep disappeared. Indications for osteotomy of the maxilla
      and mandible are: failure of conservative therapy or other forms of treatment
      with a lower morbidity, severe mandibular hypoplasia, extreme respiratory
      distress and morbid obesity. Ventral displacement of the maxilla or mandible
      eliminates the obstruction at the level of the base of the tongue. The operation
      is successful for the first year in 95% of the patients. A disadvantage is the
      temporary post-operative morbidity.

PMID- 15952499
TI  - [Fever as a sign of inflammatory syndrome in a female patient with hepatic
      haemangioma].
AB  - A 41-year-old patient presented with fever, night sweats, general malaise,
      abdominal pain, and substantial weight loss. Laboratory analysis suggested an
      inflammatory process. Diagnostic imaging revealed a hepatic haemangioma with a
      diameter of 20 cm. Because such giant haemangiomas of the liver can lead to
      inflammatory syndrome, the tumour was surgically removed. Pathological analysis
      confirmed the clinical diagnosis and evidence of extensive thrombosis and other
      vascular defects was found. Following treatment, the symptoms resolved without
      further complications. In patients with a giant haemangioma in the liver who
      present with an inflammatory syndrome, the haemangioma should be considered as
      the causal factor. For these patients, resection is the treatment of choice.

PMID- 15952500
TI  - [Systematic review of the effects of therapy in infants with the KISS-syndrome
      (kinetic imbalance due to suboccipital strain)].

PMID- 15952501
TI  - [Systematic review of the effects of therapy in infants with the KISS-syndrome
      (kinetic imbalance due to suboccipital strain)].

PMID- 15952502
TI  - [Aggression towards paediatricians and trainee paediatricians in the
      Netherlands].

PMID- 15952503
TI  - [Defecation disorders in children: treatment with colonic irrigation through an
      appendicostomy].

PMID- 15952504
TI  - [Skeletal maturation in assessing underage asylum seekers].

PMID- 15952505
TI  - [Skeletal maturation in assessing underage asylum seekers].

PMID- 15952506
TI  - [Skin cancer and other skin disorders in patients following solid organ
      transplantation].

PMID- 15952507
TI  - [Optimising patient isolation due to methicillin-resistant Staphylococcus
      aureus].

PMID- 15952508
TI  - Effect of analytical techniques on measured ambient NO2 concentrations.
AB  - A study was carried out with specific reference to NO2 measurements in three
      countries (designated as A, B and C), which use three different manual methods;
      viz. Sodium Arsenite, Greiss Saltzman and TGS-ANSA for the determination of NO2
      in ambient air. Significant deviation (up to 36 + %) was observed in measured NO,
      ion concentration when spiked samples were analyzed using these methods. Further,
      to make the data inter-comparable, exhaustive laboratory studies were carried out
      on these manual methods. Different concentration levels of NO2 were generated in
      the laboratory and analyzed by these methods simultaneously. The results were
      evaluated statistically. An interrelationship among the methods was established
      as method conversion factors (MCF). This would be useful in relating atmospheric
      concentration of NO2 among various countries, where different measurement
      techniques are adopted.

PMID- 15952509
TI  - Atrazine and alachlor inputs to surface and ground waters in irrigated corn
      cultivation areas of Castilla-Leon region, Spain.
AB  - The inputs of atrazine and alachlor herbicides to surface and ground waters from
      irrigated areas dedicated to corn cultivation in the Castilla-Leon (C-L) region
      (Spain) as related to the application of both herbicides were studied. Enzyme
      linked immunosorbent assays (ELISA) were used for monitoring the atrazine and
      alachlor concentrations in 98 water samples taken from these areas. Seventy-nine
      of the samples were of ground waters and 19 were of surface waters. The
      concentration ranges of the herbicides detected in the study period (October 1997
      October 1998) were 0.04-25.3 microg L(-1) in the surface waters and 0.04-3.45
      microg L(-1) in the ground waters for atrazine, and 0.06-31.9 microg L(-1) in the
      surface waters and 0.05-4.85 microg L(-1) in the ground waters in the case of
      alachlor. The highly significant correlation observed between the concentrations
      of both herbicides in the surface waters (r = 0.89, p < 0.001) pointed to a
      parallel transport of atrazine and alachlor to these waters. A study was made of
      the temporal evolution of the concentrations of both herbicides, and it was found
      a maximum recharge of atrazine in the ground waters for April 1998 and of
      alachlor in October 1997 and October 1998. The temporal evolution of the
      concentrations of both herbicides in surface waters was parallel. The highly
      significant correlations observed between atrazine concentrations determined by
      ELISA and by HPLC (r = 0.92, p < 0.001) and between alachlor concentrations also
      determined by both methods (r = 0.96, p < 0.001) confirmed the usefulness of
      ELISA for monitoring both herbicides in an elevated number of samples. Using
      HPLC, the presence in some waters of the alachlor ethanesulfonate (ESA)
      metabolite was found at a concentration range of 0.52-4.01 microg L(-1). However
      the interference of ESA in the determination of alachlor by ELISA was negligible.
      The inputs of atrazine and alachlor to waters found in this study, especially the
      inputs to ground waters, could pose a risk for human health considering that some
      waters, though sporadically, are even used for human consumption.

PMID- 15952510
TI  - Geostatistical uncertainty modelling for the environmental hazard assessment
      during single erosive rainstorm events.
AB  - This paper presents an environmental hazard assessment to account the impacts of
      single rainstorm variability on river-torrential landscape identified as
      potentially vulnerable mainly to erosional soil degradation processes. An
      algorithm for the characterisation of this impact, called Erosive Hazard Index
      (EHI), is developed with a less expensive methodology. In EHI modelling, we
      assume that the river-torrential system has adapted to the natural hydrological
      regime, and a sudden fluctuation in this regime, especially those exceeding
      thresholds for an acceptable range of flexibility, may have disastrous
      consequences for the mountain environment. The hazard analysis links key
      rainstorm energy variables expressed as a single-storm erosion index (EISTO),
      with impact thresholds identified using an intensity pattern model. Afterwards,
      the conditional probabilities of exceeding these thresholds are spatially
      assessed using non-parametric geostatistical techinques, known as indicator
      kriging. The approach was applied to a test site in river-torrential landscape of
      the Southern Italy (Benevento province) for 13 November 1997 rainstorm event.

PMID- 15952511
TI  - Status of heavy metals in water and bed sediments of river Gomti--a tributary of
      the Ganga River, India.
AB  - The concentrations of cadmium, chromium, copper, iron, lead, manganese, nickel,
      and zinc in water and bed sediments of river Gomti have been studied in a fairly
      long stretch of 500 km from Neemsar to Jaunpur. Grab samples of water (October
      2002-March 2003) and bed sediments (December 2002 and March 2003) were collected
      from 10 different locations following the standard methods. The river water and
      sediment samples were processed and analyzed for heavy metals viz., Cd, Cr, Cu,
      Fe, Pb, Mn, Ni, and Zn, and using ICP-AES. The heavy metals found in the river
      water were in the range: Cd (0.0001-0.0005 mg/L); Cr (0.0015-0.0688 mg/L); Cu
      (0.0013-0.0.0043 mg/L); Fe (0.0791-0.3190 mg/L); Mn (0.0038-0.0.0973 mg/L); Ni
      (0.0066-0.011 mg/L); Pb (0.0158-0.0276 mg/L); and Zn (0.0144-0.0298 mg/L)
      respectively. In the sediments the same were found in the range: Cd (0.70-7.90
      /microg/g); Cr (6.105-20.595 microg/g); Cu (3.735-35.68 microg/g); Fe (5051.485
      8291.485 micorg/g); Mn (134.915-320.45 microg/g); Ni (13.905-37.370 microg/g); Pb
      (21.25-92.15 microg/g); and Zn (1 5.72-99.35 microg/g) of dry weight
      respectively. Some physico-chemical parameters viz., pH, total solids, total
      dissolved solids, total suspended solids, dissolved oxygen, biological oxygen
      demand, chemical oxygen demand, hardness etc. were estimated as these have direct
      or indirect influence on the incidence, transport and speciation of the heavy
      metals. Based on the geoaccumulation indices, the Gomti river sediments from
      Neemsar to Jaunpur are considered to be unpolluted with respect to Cr, Cu, Fe,
      Mn, and Zn. It is unpolluted to moderately polluted with Pb. In case of Cd it
      varies from moderately polluted to highly polluted. As far as Ni is concerned the
      sediment is very highly polluted at Barabanki and Jaunpur D/s. No correlation was
      found between enrichment factor and geoaccumulation index.

PMID- 15952512
TI  - Assessing protected area effectiveness using surrounding (buffer) areas
      environmentally similar to the target area.
AB  - Many studies are based on the assumption that an area and its surrounding
      (buffer) area present similar environmental conditions and can be compared. For
      example, in order to assess the effectiveness of a protected area, the land
      use/cover changes are compared inside the park with its surroundings. However,
      the heterogeneity in spatial variables can bias this assessment: we have shown
      that most of the protected areas in Mexico present significant environmental
      differences between their interior and their surroundings. Therefore, a
      comparison that aims at assessing the effectiveness of conservation strategies,
      must be cautioned. In this paper, a simple method which allows the generation of
      a buffer area that presents similar conditions with respect to a set of
      environmental variables is presented. The method was used in order to assess the
      effectiveness of the Calakmul Biosphere Reserve, a protected area located in the
      south-eastern part of Mexico. The annual rate of deforestation inside the
      protected area, the standard buffer area (based upon distance from the protected
      area only) and the similar buffer area (taking into account distance along with
      some environmental variables) were 0.3, 1.3 and 0.6%, respectively. These results
      showed that the protected area was effective in preventing land clearing, but
      that the comparison with the standard buffer area gave an over-optimistic vision
      of its effectiveness.

PMID- 15952513
TI  - Indigenous heavy metal multiresistant microbiota of Las Catonas stream.
AB  - Las Catonas stream (Buenos Aires Metropolitan Area) receives a complex mixture of
      pollutants from point and diffuse sources because of the agricultural, industrial
      and urban land uses of its basin. Widespread detection of heavy metals exceeding
      aquatic life protection levels has occurred in monitoring reconnaissance studies
      in surface and pore water. As a result of the screening of Cu, Cd, Zn and Pb
      resistant/tolerant and culturable microbiota, B101N and 200H strains (Pseudomonas
      fluorescens or putida) were isolated and selected for further studies. They
      showed 65% Cd and 35% Zn extraction efficiency from aqueous phase. The potential
      use of these strains in wastewater treatment is currently investigated in order
      to contribute to decrease heavy metal pollution, a problem affecting every stream
      of Buenos Aires Metropolitan Area.

PMID- 15952514
TI  - Environmental monitoring of heavy metals in Bulgarian Black Sea green algae.
AB  - Fe, Mn, Cu, Pb and Cd concentration distribution in six green macroalgae species
      from the Bulgarian Black Sea coast were determined. The measurement of these
      metals was carried out during six seasons from 1996 to 2002 using atomic
      absorption spectrometry (AAS). Samples were collected from eight different sites
      Shabla, Kaliakra, Tuzlata, Ravda, Ahtopol and Sinemoretz. The obtained heavy
      metal (HM) data (mean values microg/g) for all algae are: 650 +/- 100 for Fe, 184
      +/- 15 for Mn, 5.6 +/- 0.5 for Cu, 3.3 +/- 0.3 for Pb and 1.1 +/- 0.2 for Cd. The
      obtained HM contents indicate that different species demonstrate various degree
      of metal accumulation and the obtained higher values in the northern sector of
      the studied zone can be attributed to the discharge influence of the big rivers,
      entering the Black Sea-Danube, Dnyepr, Dnester and local pollutant emissions. All
      data show that there is no serious contamination in green macroalgae with heavy
      and toxic metals along the whole Bulgarian Black Sea coast.

PMID- 15952515
TI  - Monitoring of butter and ghee (clarified butter fat) for pesticidal contamination
      from cotton belt of Haryana, India.
AB  - Butter (45) and ghee (55) samples were collected from rural and urban areas of
      cotton growing belt of Haryana and analysed for detecting the residues of
      organochlorine, synthetic pyrethroid and organophosphate insecticides. The
      estimation was carried out by using multi residue analytical technique employing
      GC-ECD and GC-NPD systems equipped with capillary columns. Butter samples were
      comparatively more contaminated (97%) than ghee (94%), showing more contamination
      with organochlorine insecticides from urban samples. About 11% samples of butter
      showed endosulfan residues above MRL value and 2% samples had residues of
      synthetic pyrethroids and organophosphates each above their respective MRL
      values. In ghee, residues of HCH & DDT both and of endosulfan exceeded the MRL
      values in 5 and 20% samples, respectively. Among organophosphates, only
      chlorpyriphos was detected with 9% samples showing its residue above MRL value.
      Irrespective of contamination levels, residues above the MRL values were more in
      ghee. More extensive study covering other agricultural regions/zones of Haryana
      has been suggested to know the overall scenario of contamination of milk
      products.

PMID- 15952516
TI  - Study on the effect of porous fence on air quality and traffic noise level around
      a double-decked road structure. Evaluation by numerical model.
AB  - Fence for traffic noise control sometimes causes adverse effect on air pollution.
      Thus in this study, performance of porous fence as a tool for control of both air
      pollution and noise pollution was evaluated. A two-dimensional numerical model
      for flow and pollutant concentration and an analytical model for traffic noise
      were utilized in the analysis of a double-decked road structure with fences only
      at ground (Case 1) and at both ground and upper deck (Case 2). Porous fences were
      assumed only at the ground level since the solid fences at the upper deck usually
      leads to desirable result on air pollution. Effects of the variable porosity on
      air quality and noise level near road were evaluated. Obtained results showed:
      (1) flow pattern in leeward of fence was drastically changed at 40-50% porosity
      in Case 1 and 50% in Case 2. The porosity larger than 40% excluded presence of a
      circulation behind the fence. (2) Effect of porous fence on air pollution was
      different in Cases 1 and 2. In Case 1, the porous fence generally resulted in the
      reduction of air pollution at the ground level; on the other hand, in Case 2, it
      rather led to increase of the concentration. (3) Traffic noise level was also
      largely changed by the porosity of the fence; an example of simultaneous
      evaluation of the effects of porous fence on both air and noise pollution in Case
      1 showed that the fence of 60% porosity leads to reduction of air pollution by
      20% compared with solid fence case, and reduction of noise pollution by 4-6% in
      dB compared with no fence case, at 1 m high and 10 m from the road.

PMID- 15952517
TI  - Using aerial video to train the supervised classification of Landsat TM imagery
      for coral reef habitats mapping.
AB  - Management of coral reef resources is a challenging task, in many cases, because
      of the scarcity or inexistence of accurate sources of information and maps.
      Remote sensing is a not intrusive, but powerful tool, which has been successfully
      used for the assessment and mapping of natural resources in coral reef areas. In
      this study we utilized GIS to combine Landsat TM imagery, aerial photography,
      aerial video and a digital bathymetric model, to assess and to map submerged
      habitats for Alacranes reef, Yucatan, Mexico. Our main goal was testing the
      potential of aerial video as the source of data to produce training areas for the
      supervised classification of Landsat TM imagery. Submerged habitats were
      ecologically characterized by using a hierarchical classification of field data.
      Habitats were identified on an overlaid image, consisting of the three types of
      remote sensing products and the bathymetric model. Pixels representing those
      habitats were selected as training areas by using GIS tools. Training areas were
      used to classify the Landsat TM bands 1, 2 and 3 and the bathymetric model by
      using a maximum likelihood algorithm. The resulting thematic map was compared
      against field data classification to improve habitats definition. Contextual
      editing and reclassification were used to obtain the final thematic map with an
      overall accuracy of 77%. Analysis of aerial video by a specialist in coral reef
      ecology was found to be a suitable source of information to produce training
      areas for the supervised classification of Landsat TM imagery in coral reefs at a
      coarse scale.

PMID- 15952518
TI  - Measurements of ozone concentrations in Zagreb.
AB  - Ozone concentrations were measured in Zagreb at four sites from May 1999 to April
      2001 in order to categorize the air quality with respect to ozone. In the summer
      of 2000, the ozone measurements were also extended to four sites in the suburbs
      of Zagreb. Methods of active and passive sampling with nitrite ion as a reagent
      were used. In the northern part of the town ozone was analyzed by an automatic
      device. Automatic device measurements in the years 1999 and 2000 showed that
      hourly averages of ozone concentrations did not exceed the Croatian recommended
      value of the 98th percentile (180 micro/g m(-3)). Over the two-year period, 24-h
      averages occasionally exceed 110 microg m(-3) in city center and in the northern
      part of the town. Regardless of these isolated examples, ozone was well within
      acceptable concentrations. Ozone concentrations measured in summer 2000 were
      higher in the suburbs of Zagreb than in the city. The 98th percentile values
      higher than 110 microg m(-3) were recorded at three sites.

PMID- 15952519
TI  - Morphological and physiological damage by surfactant-polluted seaspray on Pinus
      pinea and Pinus halepensis.
AB  - This paper reports morphological and physiological damage caused by polluted
      seaspray to coastal pine forests in Liguria (Northern Italy) and suggests the
      most reliable parameters for surfactant-pollution biomonitoring. Concentrations
      of surfactants in surface seawater, seaspray, and that deposited on Pinus
      halepensis and Pinus pinea needles were determined in samples from five sites.
      Decline of the pines in the Western part of Liguria was greater than in the East,
      and was associated with higher surfactant levels deposited on the crowns.
      Chloride content of needles was higher in damaged pines, even if it did not reach
      toxic levels. Stomata micromorphologies did not differ between species in the
      crown parts facing the sea, while differences were significant in the back crown
      parts that were not directly exposed to polluted sea breezes. Water content and
      noon water potential indicated interference in water relations of damaged trees.
      In conclusion, none of the investigated parameters was by itself a comprehensive
      index of surfactant damage. A simultaneous survey of several parameters is
      suggested to investigate the impact of surfactants on coastal vegetation. The
      most useful parameters were: directionality of crown damage, surfactant
      depositions on the needles, chloride accumulation in the needles, structural
      injury to epistomatal chambers, needle water content and potential.

PMID- 15952520
TI  - Metal pollution assessment of sediment and water in the River Hindon, India.
AB  - The metal pollution in water and sediment of the River Hindon in western Uttar
      Pradesh (India) was assessed for Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. The metal
      concentrations in water showed wide temporal variation compared with bed sediment
      because of variability in water discharge and variations in suspended solid
      loadings. Metal concentrations in bed sediments provided a better evaluation of
      the degree and the extent of contamination in the aquatic environment, Santagarh
      and Atali being the most polluted sites of the river. The ratio of heavy metals
      to conservative elements (Fe, Al, etc.) may reveal the geochemical imbalances due
      to the elevated metal concentrations normally attributed to anthropogenic
      sources. Metal/A1 ratios for the bed sediments of the river Hindon were used to
      determine the relative mobility and general trend of relative mobility occurred
      Fe > Mn > Zn > Cr > Ni > Pb > Cu > Cd.

PMID- 15952521
TI  - Relationship between bird abundances and landscape characteristics: the influence
      of scale.
AB  - Scale is important to consider when investigating effects of the environment on a
      species. Breeding Bird Survey (BBS) data and landscape metrics derived from
      aerial photographs were evaluated to determine how relationships of bird
      abundances with landscape variables changed over a continuous range of 16 spatial
      scales. We analyzed the average number of birds per stop (1985-1994) for five
      songbird species (family Cardinalidae) for each of 50 stops on 198 BBS transects
      throughout six states in the Central Plains, USA. Land along each transect was
      categorized into six cover types, and landscape metrics of fractal dimension (a
      measure of shape complexity of habitat patches), edge density, patch density, and
      percent area were calculated, with principal components used to construct
      composite environmental variables. Associations of bird abundances and landscape
      variables changed in accordance with small scale changes. Abundances of three
      species were correlated with edge density and one with component I, which
      subsumes initial variables of patch density for urban, closed forest, open
      forest, and open country. Fractal dimension and component II (summarizing amount
      of closed forest versus open country) were associated with the most species.
      Correlation patterns of fractal dimension with northern cardinal (Cardinalis
      cardinalis) and painted bunting (Passerina ciris) abundances were similar, with
      highest correlations at intermediate to small scales, suggesting indirectly that
      these species thrive in areas where local habitat conditions are most important.
      Multiscale analysis can provide insight into the spatial scale(s) at which
      species respond, a topic of intrinsic scientific interest with applied
      implications for researchers establishing protocols to assess and monitor avian
      populations.

PMID- 15952522
TI  - Uncertainty assessment of VOC emissions from paint in The Netherlands using the
      NUSAP system.
AB  - We demonstrate an innovative approach to uncertainty assessment known as the
      NUSAP system, to assess qualitative and quantitative uncertainty for the case of
      emissions of volatile organic compounds (VOC) from paint in The Netherlands.
      Using expert elicitation, we identified key sources of error, critical
      assumptions, and bias in the monitoring process. We assessed pedigree and
      probabilistic uncertainty of all input quantities. We used four pedigree criteria
      to assess the strength of the knowledge base: proxy representation, empirical
      basis, methodological rigour and degree of validation. Using Monte Carlo
      analysis, we assessed sensitivity and propagation of uncertainty. Results for
      sensitivity and pedigree were combined in a 'NUSAP Diagnostic Diagram', which
      effectively highlighted the assumption for VOC percentage of imported paint as
      the weakest spot in the monitoring of VOC emissions. We conclude that NUSAP
      facilitates systematic scrutinization of method and underlying assumptions and
      structures creative thinking on sources of error and bias. It provides a means to
      prioritise uncertainties and focus research efforts on the potentially most
      problematic parameters and assumptions, at the same time identifying specific
      weaknesses in the knowledge base. With NUSAP, nuances of meaning about quantities
      can be conveyed concisely and clearly, to a degree that is not possible with
      statistic methods only.

PMID- 15952523
TI  - Risk-based prioritization of air pollution monitoring using fuzzy synthetic
      evaluation technique.
AB  - Air pollution monitoring programs aim to monitor pollutants and their probable
      adverse effects at various locations over concerned area. Either sensitivity of
      receptors/location or concentration of pollutants is used for prioritizing the
      monitoring locations. The exposure-based approach prioritizes the monitoring
      locations based on population density and/or location sensitivity. The hazard
      based approach prioritizes the monitoring locations using intensity
      (concentrations) of air pollutants at various locations. Exposure and hazard
      based approaches focus on frequency (probability of occurrence) and potential
      hazard (consequence of damage), respectively. Adverse effects should be measured
      only if receptors are exposed to these air pollutants. The existing methods of
      monitoring location prioritization do not consider both factors (hazard and
      exposure) at a time. Towards this, a risk-based approach has been proposed which
      combines both factors: exposure frequency (probability of occurrence/exposure)
      and potential hazard (consequence). This paper discusses the use of fuzzy
      synthetic evaluation technique in risk computation and prioritization of air
      pollution monitoring locations. To demonstrate the application, common air
      pollutants like CO, NOX, PM10 and SOX are used as hazard parameters. Fuzzy
      evaluation matrices for hazard parameters are established for different locations
      in the area. Similarly, fuzzy evaluation matrices for exposure parameters:
      population density, location and population sensitivity are also developed.
      Subsequently, fuzzy risk is determined at these locations using fuzzy
      compositional rules. Finally, these locations are prioritized based on
      defuzzified risk (crisp value of risk, defined as risk score) and the five most
      important monitoring locations are identified (out of 35 potential locations).
      These locations differ from the existing monitoring locations.

PMID- 15952524
TI  - A screening procedure for identifying acid-sensitive lakes from catchment
      characteristics.
AB  - Monitoring of Wilderness lakes for potential acidification requires information
      on lake sensitivity to acidification. Catchment properties can be used to
      estimate the acid neutralizing capacity (ANC) of lakes. Conceptual and general
      linear models were developed to predict the ANC of lakes in high-elevation (> or
      = 2170 m) Wilderness Areas in California's Sierra Nevada mountains. Catchment-to
      lake area ratio, lake perimeter-to-area ratio, bedrock lithology, vegetation
      cover, and lake headwater location are significant variables explaining ANC. The
      general linear models were validated against independently collected water
      chemistry data and were used as part of a first stage screen to identify
      Wilderness lakes with low ANC. Expanded monitoring of atmospheric deposition is
      essential for improving the predictability of lake ANC.

PMID- 15952525
TI  - The use of Mytilus galloprovincialis acetylcholinesterase and glutathione S
      transferases activities as biomarkers of environmental contamination along the
      northwest Portuguese coast.
AB  - With the aim of using Mytilus galloprovincialis acetylcholinesterase (AChE) and
      glutathione S-transferases (GST) activities as biomarkers of environmental
      contamination in risk assessment studies along the northwest Portuguese coast,
      the objective of this study was to provide background information related to: (1)
      baseline values of these enzymatic activities both in reference and contaminated
      areas and their responsiveness as indicators of exposure to environmental
      contaminants; (2) the importance of seasonal variations of such biomarkers in M.
      galloprovincialis along this area. For this, the activity of these enzymes was
      seasonally determined in mussels collected from four sites, including a reference
      and three stations with different contamination sources along the referred area.
      Statistically significant differences on both enzymatic activities were found
      among the four sampling stations, at the four sampling periods. In comparison to
      the reference station, lower AChE and higher GST activity values were found in
      mussels collected in stations potentially contaminated by pesticides and
      domestic/industrial effluents and in mussels collected in the vicinity of an oil
      refinery and an industrial/mercantile harbour, respectively. The results obtained
      in this work highlighted the potential suitability of these biomarkers to be used
      as components of environmental monitoring programs in risk assessment studies
      along the northwest Portuguese coast. Since a seasonal variation in both
      enzymatic activities was found, the possible implications of such variability in
      the use of these enzymes as environmental biomarkers are also discussed.

PMID- 15952526
TI  - Investigation of MTBE and aromatic compound concentrations at a gas service
      station.
AB  - Methyl tert-butyl ether (MTBE) has been used as a fuel additive at levels of 2
      11% in Taiwan for the past decade. The purpose of this additive is to enhance the
      octane, replace the use of lead-based anti-knock gasoline additives and reduce
      aromatic hydrocarbons. However, it is possible that oxygenated fuel has a
      potential health impact. To determine the air quality impact of MTBE,
      measurements were made of ambient MTBE and other gasoline constituents at a
      service station. Additionally, environmental conditions (wind speed, wind
      direction, and temperature, etc.) that could affect concentrations of emission
      constituents were measured. Gas samples were analyzed for target MTBE and
      volatile organic compounds, e.g., benzene and toluene. Ambient samples were
      collected using Tenax adsorbent tubes for mass spectrometric analysis at a
      service station located in Changhua County, Taiwan. The resulting measured
      ambient air concentrations were compared with Taiwan's regulatory standards for
      hazardous air pollutants. Subsequently, the factors controlling the formation of
      high-VOC levels at the service station and in the residential neighborhoods were
      identified. Additionally, the results can provide the Environmental Protection
      Agency (EPA) of Taiwan with useful information and prompt them to mandate this
      gas service station to install a refueling vapor recovery system.

PMID- 15952527
TI  - Pollution and genetic structure of North American populations of the common
      dandelion (Taraxacum officinale).
AB  - Assessing the genetic structure of natural populations differentially impacted by
      anthropogenic contaminants can be a useful tool for evaluating the population
      genetic consequences of exposure to pollution. In this study, measures of genetic
      diversity at variable-number-tandem-repeat loci in six dandelion populations (3
      urban and 3 rural) showed patterns that may have been influenced by exposure to
      environmental contaminants. Mean genetic similarity among individuals within a
      population was significantly and positively correlated with increasing levels of
      airborne particulate matter (< or = 10 microm, PM10) and soil concentrations of
      four metals (Cd, Fe, Ni and Pb). In addition, mean genetic similarity was always
      significantly higher at the urban sites compared to rural sites. There was a
      significant negative correlation between the number of genotypes at a site and
      increasing amounts of PM10, concentrations of five soil metals (Cd, Cu, Fe, Ni
      and Pb), leaf tissue levels of Fe and a significant positive correlation between
      the extent of clonality at a site and levels of PM10 and soil concentrations of
      five metals (Cd, Cu, Fe, Ni and Pb). Although, this study does not directly
      establish a causal link between the specific contaminants detected at the study
      sites and differences in genetic diversity, our data are consistent with the
      hypothesis that pollution-induced selection has contributed in some fashion to
      the lower genetic diversity found at the urban sites.

PMID- 15952528
TI  - Indoor air quality at Salarjung Museum, Hyderabad, India.
AB  - Deterioration of art objects at Salarjung Museum has been noticed such as
      blackening of white and pink pigments of Indian miniature paintings and other
      objects like pigments, paints, varnishes, coatings, silver ware, zari works,
      textiles, which are displayed in museum galleries. The cause of deterioration of
      the artifacts is attributed to air pollution. The outdoor air pollution levels
      with respect to suspended particulate matter, sulphur dioxide, oxides of
      nitrogen, ammonia, aldehydes and oxidants are observed to be high when compared
      with background environment and ambient air quality standards for sensitive
      areas. The indoor air quality levels in terms of various parameters including
      temperature and relative humidity (RH) observed to be more than the threshold
      limits. The climatic conditions coupled with polluted indoor air are the main
      causes for the deterioration of art objects. Hence remedial measures are
      suggested to avoid further deterioration of objects.

PMID- 15952529
TI  - Air quality status of an open pit mining area in India.
AB  - This investigation presents the assessment of ambient air quality carried out at
      an open pit coal mining area in Orissa state of India. The 24-h average
      concentrations of suspended particulate matter (SPM), respirable particulate
      matter (RPM, particles of less than 10 microm aerodynamic diameter), sulphur
      dioxide (SO2) and oxides of nitrogen (NO(x)) were determined at regular interval
      throughout one year at 13 monitoring stations in residential area and four
      stations in mining/industrial area. During the study period, the 24-h and annual
      average SPM and RPM concentrations exceeded the respective standards set in the
      Indian ambient air quality standard (NAAQS) protocol in most of the residential
      and industrial areas. However, the 24-h and annual average concentrations of SO2
      and NO(x) were well within the prescribed limit of the NAAQS in both residential
      and industrial areas. A management strategy is formulated for effective control
      of particulate matter at source and other mitigative measures are recommended
      including implementation of green belts around the sensitive areas.

PMID- 15952530
TI  - A variance estimator for constrained estimates of change in relative categorical
      frequencies.
AB  - Consistent estimators of change and state becomes an issue when sample data come
      from a mix of permanent and temporary observation units. A joint maximum
      likelihood estimator of state and change creates estimates of state that depend
      on antecedent viz. posterior survey results and may differ from estimates of
      state derived from a single-date analysis of the sample data. A constrained
      estimator of change in relative categorical frequencies that eliminates this
      potential inconsistency is proposed and a model based estimator of their sampling
      variance is developed. The performance of the constrained estimator is quantified
      against six criteria and a joint maximum likelihood estimator in simulated
      sampling from 15 populations with three combinations of permanent and temporary
      samples, four to six categorical class attributes, and constant size between
      sampling dates. Bias of the constrained estimators was negligible but larger than
      for joint maximum likelihood estimators. Mean absolute deviations and variances
      of constrained estimators were generally at par with the joint estimators.
      Constrained estimators of root mean square errors and achieved coverage of
      nominal confidence intervals of constrained estimators were occasionally better.
      A generalized variance function for the constrained estimates of change is
      provided as a computational shortcut.

PMID- 15952531
TI  - Profile of PAHs in the diesel vehicle exhaust in Delhi.
AB  - A preliminary study to determine the profile of PAHs in the exhaust of diesel
      vehicles plying on Delhi roads was conducted. Two different types of diesel
      vehicles (buses and trucks) with different age groups were selected for sampling
      purpose. The concentration of Total PAHs (sigma12 PAHs) was found to be 50.76 +/-
      6.62 and 57.72 +/- 4.15 mg/g in the exhaust of buses and trucks, respectively.
      The levels of PAHs were found to be high in trucks as compared to that of buses.
      The total PAHs concentration in the present study was found to be higher as
      compared to other studies. Such a high concentration could be attributed to
      different parameters like the age of the vehicles, driving conditions, the fuel
      quality and the emission standards.

PMID- 15952533
TI  - A survey of trace metals in vegetation, soil and lower animal along some selected
      major roads in metropolitan city of Lagos.
AB  - The concentration of trace metals (Cd, Cu, Pb and Zn) in a total of 144 samples
      of grass, soil and lower animal (earthworm, Lybrodrilus violaceous) were
      collected and analysed for their metallic content. Levels of cadmium ranged from
      0.01-0.07 microg g(-1); 0.01-0.12 microg g(-1) and from trace-0.05 microg g(-1)
      dry weight for plant, soil and animal samples respectively. Mean concentration of
      copper ranged 0.10-1.48 microg g(-1); 0.10-2.90 microg g(-1) and 0.01-0.08 microg
      g(-1) for samples in similar order as above. The levels of Pb varied from 0.01
      0.14 microg g(-1); 0.02-0.23 microg g(-1) and from trace-0.07 microg (g-1) while
      that of Zn ranged from 0.19-1.80 microg g(-1); 0.51-3.35 microg g(-1) and 0.01
      0.08 microg g(-1) also in the same order of samples as mentioned above. Levels of
      metals in soil samples were higher than the background levels with the exception
      of Zn but lower than European Union (EU) limits. The results generally revealed
      the presence of metals in plant and animal samples and metal dynamics up the food
      chain is highly possible. Acceptable recoveries of the spiking experiment
      validate the experimental protocol.

PMID- 15952534
TI  - [Primary antiphospholipid syndrome and cerebrovascular disturbances].
AB  - Neurological, including cecbrovascular, disorders frequently emerge in primary
      antiphospholipid syndrome (PAS). Clinical peculiarities of PAS were studied in
      113 patients with cerebrovascular disturbances. Its had mainly ischemic
      patogenesis. Structure of cerebrovascular disorders was as follows: stroke (33%
      cases), transient ischemic lesions (10%), its combination (57%), thrombosis of
      brain venous sinuses (3%), vascular dementia (27%). Besides it were found
      epileptic seizures, peripheral neuropathy, headache, chorea and some symptoms of
      myasthenia, parkinsonism, multiple sclerosis and psychotic disorders. In all
      cases antibodies to phospholipids have been detected. Secondary prophylaxis
      includes regular use of anticoagulants and small doses of aspiriny.

PMID- 15952532
TI  - Foliar phenolics in sugar maple (Acer saccharum) as a potential indicator of
      tropospheric ozone pollution.
AB  - Tropospheric O3 has been implicated in the declining health of forest ecosystems
      in Europe and North America and has been shown to have negative consequences on
      human health. We have measured tropospheric ozone (O3) in the lower canopy
      through the use of passive monitors located in five woodlots along a 150 km urban
      rural transect, originating in the large urban complex of Toronto, Canada. We
      also sampled foliage from 10 mature sugar maple trees in each woodlot and
      measured the concentration of a number of phenolic compounds and macronutrients.
      O3 concentrations were highest in the two rural woodlots, located approximately
      150 km downwind of Toronto, when compared to the woodlots found within the
      Greater Toronto Area. Foliar concentrations of three flavonoids, avicularin,
      isoquercitrin, and quercitrin, were significantly greater and nitrogen
      concentrations significantly lower at these same rural woodlots, suggesting some
      physiological disruption is occurring in those sites where exposure to
      tropospheric O3 is greater. We suggest that foliar phenolics of sugar maple may
      be a biochemical indicator of tropospheric ozone exposure.

PMID- 15952535
TI  - [Somato-autonomic symptoms in different types of seasonal affective disorders].
AB  - Ninety-seven patients (76 female, mean age 31,2 years and 21 male, mean age 34,6
      years) who had a diagnosis (according to ICD-10) of seasonal affective disorder
      (SAD), depressive episode, have been studied. It is shown that SAD included at
      least two types of depression with different somato-autonomic symptoms. They were
      classified as SAD with anesthetic somato-autonomic complex (type 1) and SAD with
      hyperesthetic somato-autonomic complex (type 2). The authors set up a hypothesis
      that a particular personality predisposition (constitutional or acquired) in a
      form of hypochondriac diathesis (type 1) and neuropathic diathesis with weather
      and climate sensitivity (type 2) can be considered as a causative factor of
      seasonality of depression and predomination of somato-autonomic symptoms in its
      structure.

PMID- 15952536
TI  - [3-year results of clinical and immunological monitoring of patients with
      multiple sclerosis treated by copaxone].
AB  - Tipe 1 T-helper cells are of importance in development of multiple sclerosis
      (MS). Copaxone (TEVA, Israel) is one of the preventive drugs, which modifies T
      helpers activity. Thirty-three patients with MS were treated by copaxone for 2
      years and 13 patients--for 3 years. Clinical and immunological parameters were
      examined: amount of CD3+, CD4+, CD8+, CD16+, CD22+, CD95+, CD25+ lymphocytes, HLA
      D+ cells, IgG, IgA, IgM and phagocytosis. During the treatment course, mean rate
      of relapses decreased from the pretreatment value from 1.26 +/- 0.11 to 0.59 +/-
      0.11 in the first year and 0.28 +/- 0.07 in the second one. After 3 years no
      relapses were observed in 13 patients. Relapse rate was the highest in the first
      3-6 months. But after 3 months there was an increase of CD22+ cells that
      persisted for all the period of the study. After a year of the treatment, a level
      of IgM, IgG, IgA and CD95+ cells has raised significantly, with decreasing of a
      number of CD4+ and CD8+ cells. The authors suggest that immunological shift is
      related to mechanism of copaxone action determining its positive effect i.e.
      reducing of frequency of MS relapses.

PMID- 15952537
TI  - [Topamax in the treatment of epilepsy].
AB  - To specify efficacy of topamax in different types of epileptic seizures and its
      influence on patient's quality of life (QL), the drug was assigned to 38
      patients, aged 18-69 years, as mono- and polytherapy (in combination with other
      anticonvulsive medications). Topamax dosages ranged from 25-50 mg at a base-line
      to 600 mg. Treatment duration was 6-18 months. Positive effect of different
      extent was achieved in 95.7% patients. A seizures frequency decreased by 25% in
      17.4% patients; by 50%--in 8.7%; by 75%--in 43.5%; a complete disappearance of
      seizures was detected in 30.4%. The results confirmed the earlier data received
      by the authors that topamax was most effective in generalized convulsive, partial
      and secondary generalized seizures. It exerts a less pronounced effect in
      myoclonic seizures and absences. After topamax treatment, a total QL index
      measured by WHO questionnaire increased by 5.2%. The drug is well tolerated and
      does not affect cognitive functions of the patients. It is concluded that
      currently topamax is one of the most effective antiepileptic medications.

PMID- 15952538
TI  - [Evaluation of stress tolerance in the neurological patients].
AB  - A purpose of the study was to develop the Stress Tolerance Scale (STS) and to
      assess its diagnostic efficacy in neurological clinical practice. The theoretical
      ground for stress tolerance measurement is the concept of personal environmental
      interaction as a process including phases of the subjective stress event
      appraisal, active reaction and subjective result appraisal. The STS encompasses
      the response items of the descriptions of the accomplished and unaccomplished
      person-environment and self-personal relations that result in stress overcoming
      or in stress maintenance, respectively. Within each group, the additional
      variants of the transactions were specified according to their space-temporal
      characteristics. Data sets from 112 healthy people and 247 patients (60 with
      chronic tension headache, 72 with chronic low back pain, 51 with myasthenia
      gravis, 14 with progressive muscular dystrophy, 27 with hereditary polyneuropathy
      and 23 with torticollis) have been analyzed. The validity and quiantitation of
      the STS were determined by Rasch analysis and comparison of the results with
      those of total STS score and subscale scores of the Hospital Anxiety and
      Depression Scale and Russian brief version of MMPI. All correlations were at a
      level of significance. A decrease of stress tolerance was found in patients with
      chronic pain syndromes and torticollis. The results indicate that the STS allows
      assessing stress tolerance and a structure of person-environment interactions
      used by a patient. It can be utilized for optimization of short-term
      psychotherapy of neurological patients.

PMID- 15952539
TI  - [Magnetic-resonance tomography in differential diagnosis of brain lesions in
      demyelinating and systemic autoimmune diseases].
AB  - An aim of the study was to establish MRT signs that may be useful for
      differential diagnosis of multiple sclerosis (MS). Three groups of patients have
      been examined: 300 patients with MS, 35 with demyelinating diseases (acute
      disseminated encephalomyelitis, neuromyelitis optica--Devic's syndrome); 90
      patients with systemic autoimmune diseases (systemic lupus erythematosus, primary
      antiphospholipid syndrome, sclerodermatitis, Sjugren's syndrome, autoimmune
      thyroiditis, vasculitis and vasculopathy). Classification of MRT syndromes in MS
      and their frequency are presented: syndrome of chronic inflammatory demyelination
      (79%), syndrome of acute inflammatory demyelination (9%), syndrome of multifocal
      degenerative leucoencephalopathy (8%), syndrome of combined multifocal diffusive
      leucoencephalopathy (4%). The similarity and differences in MRT semiotics of the
      above diseases and MS are described.

PMID- 15952540
TI  - [Clinical genetic characteristics of hereditary extrapyramidal diseases in
      Saratov region].

PMID- 15952541
TI  - [Vitamin activity of cerebrolysin].

PMID- 15952542
TI  - [Possibility of the regulation of venous outflow from deep brain structures].

PMID- 15952543
TI  - [The clinical and immunological aspects of the effects of phenotropil on
      consequences of stroke].

PMID- 15952544
TI  - [Trichotillomania in patients with eating disorders].

PMID- 15952545
TI  - [Differential diagnosis of multiple sclerosis and some systemic connective tissue
      diseases with vasculitis].

PMID- 15952546
TI  - [Current views on pathogenesis, diagnosis and treatment of chorea minor].

PMID- 15952547
TI  - [Use of beta-interferon in the treatment of multiple sclerosis: high-rate
      injectable dose therapy].

PMID- 15952548
TI  - The vertical dimension: the "low-angle" patient.
AB  - The patient who has a diminished anterior facial height and excess posterior
      facial height must be treated with a "different" diagnosis and treatment plan.
      The mandibular incisors must be left in their pretreatment positions--or facial
      balance will be compromised. They must not be proclined to eliminate crowding or
      to level a curve of Spee. The three most common diagnostic "schemes" for these
      patients are: (1) third molar extraction; (2) maxillary first premolar and
      mandibular third molar extraction; and (3) maxillary first premolar and
      mandibular second premolar extraction. This article will attempt to explain why
      certain diagnostic decisions are made. Case reports are used to illustrate the
      three most common treatment plans.

PMID- 15952549
TI  - Relapse after orthodontics and orthognathic surgery.
AB  - A combined orthodontic and surgical approach is often the treatment of choice for
      the correction of severe dentofacial deformities. Numerous orthognathic surgical
      procedures have been developed for this treatment. It is clear that certain
      orthognathic surgical procedures have a tendency to relapse; many studies have
      been conducted in an attempt to create a pattern of predictability and a
      prognosis of stability. This article reviews the literature briefly and presents
      four cases in which the combined surgical and orthodontic approach produced less
      than satisfactory results. The small number of patients does not permit
      statistical evaluation or firm conclusions regarding the occurrence and the
      etiology of relapse in general. This article underlines the importance of long
      term follow-up for all patients treated with a combination of orthodontics and
      orthognathic surgery.

PMID- 15952550
TI  - Psychological impact of self-image dissatisfaction after orthognathic surgery: a
      case report.
AB  - AIMS: The number of patients who need treatment for dentofacial abnormalities has
      increased over the past 30 years. Facial alterations can influence both the
      patient's self-confidence and his interpersonal relationships, possibly
      generating emotional or physical handicaps. This qualitative study discusses a
      patient's psychological dissatisfaction with a postoperative outcome, despite the
      esthetic and functional success of the treatment. METHODS: The Oral Health Status
      Questionnaire, Post Surgical Satisfaction Questionnaire, Illness Behavior
      Questionnaire, and a clinical interview were used for the research methodology.
      RESULTS: Oral surgeons are encouraged to identify, presurgery, the patient's true
      motivation. An efficacious behavioral model is proposed that might help the
      patient transition through the consequences stages of the psychosocial changes
      associated with facial reconstructive surgery. CONCLUSION: Orthognathic surgery
      involves more than the correction of a physical problem. The psychological needs
      of the patient must be recognized and acknowledged, and communication between
      surgeons and patients is essential. It is important to understand that any
      surgical treatment that modifies body image could generate psychological
      disorders for some patients. Early surgical intervention and a referral for
      psychological counseling may reduce long-term morbidity. This case report should
      alert attending surgeons and orthodontists to possible unfavorable psychological
      sequelae.

PMID- 15952552
TI  - Management of facial dysmorphogenesis in nemaline myopathy: a case report.
AB  - Nemaline myopathy is a rare congenital muscle disease, which is clinically and
      genetically heterogeneous. Both neonatal and adult onset can occur; in those with
      neonatal onset, the resulting muscle weakness can also afflict the facial
      musculature and hence influence facial growth and development. This article
      reports on a case in which no orthodontic intervention was undertaken during
      childhood and adolescence. An early decision was made to treat the facial
      dysmorphogenesis surgically once skeletal maturity had been reached. The authors
      discuss and illustrate the untreated facial growth in this condition and the
      surgical outcome following orthodontic treatment and orthognathic surgery.

PMID- 15952551
TI  - Premolar bracket position revised: proximal and occlusal contacts assessment.
AB  - AIM: To assess the effect of conventional bracket slot vertical position (4 mm
      from incisal edge) on crown spatial orientation relative to adjacent and opposing
      teeth through proximal contact balance and occlusal contacts assessment. MATERIAL
      AND METHODS: Forty patients were divided into two groups; in the first group,
      brackets were bonded 4 mm from the intact incisal edge; in the second group,
      bracket position was determined individually by transferring the maximum
      embrasure difference to the bracket slot height difference. The difference of
      proximal contacts between premolars and molars was measured. Bite registration
      with the use of articulating paper was also performed on all patients. Traces
      indicating contact between premolar maxillary lingual cusps and opposing
      mandibular fossa of the first and second premolars were evaluated. Differences
      with respect to the distribution of unbalanced proximal contacts and negative
      contacts between the two bonding schemes were analyzed with the chi-square test
      at P = .05 level of significance. RESULTS: Aligning the bracket slot with the
      center of the clinical crown (FA point) consistently produced unbalanced proximal
      contacts in excess of 1 mm, as well as increased absence of occlusal contacts.
      CONCLUSION: Positioning the bracket slot on the center of the premolar crown may
      result in marginal ridge discrepancy between the premolars and molars and lack of
      occlusal contacts with opposing dentition. This may be due to the height
      difference noted between the buccal and lingual cusp of the premolars, as well as
      variation in molar tube or band placement. Functional occlusal analysis should be
      integrated in the finishing stages of treatment to facilitate proper premolar
      crown position.

PMID- 15952553
TI  - Measuring the cost, effectiveness, and cost-effectiveness of orthodontic care.
AB  - AIM: To determine the relative effectiveness and cost-effectiveness of
      orthodontic treatment per case in one "fee for item" and two different types of
      salaried orthodontic clinics. SUBJECTS AND METHODS: This prospective study
      recruited a random sample of six self-employed orthodontists (fee-for-item) and
      six orthodontists from both hospital and community clinics (salaried services).
      One hundred patients were followed to completion of orthodontic care.
      Questionnaires were employed to determine cost of treatment from the clinicians'
      and patients' points of views. Four cost-effectiveness models were developed.
      RESULTS: Complete records of outcome were available for 1,087 patients, but only
      789 had complete data on costing. Three of the four cost-effectiveness models
      indicated similar rankings for the 18 clinicians. The most cost-effective service
      was provided by clinicians working in community clinics, followed by clinicians
      working in hospitals, then self-employed clinicians. The preferred cost-effective
      model takes into consideration the initial need and successful outcome of
      orthodontic treatment. CONCLUSION: Cost-effectiveness models have been developed
      to quantify the performance of individual clinicians working in self-employed and
      salaried clinics. Costs and effectiveness of the clinicians in each clinical
      setting show considerable variation.

PMID- 15952554
TI  - Class II deep bite faces: one-phase or two-phase treatment?
AB  - Timing is the key for successful and stable results in Class II patients. Most
      low-angle patients are treated during the mixed dentition in two phases:
      orthopedics, then orthodontics. The vertical discrepancy differentiates the
      patient who will need extraction, the high-angle case, from those who should be
      treated through nonextraction, the low-angle case. Treatment of these latter
      patients necessitates expansion of the soft tissues. In the authors' practice,
      70% of cases are treated nonextraction. This new concept for Class II treatment
      makes the Class II mechanics less traumatic because the occlusal correction
      requires less anchorage preparation. Most low-angle cases treated with two-phase
      treatment do not require surgical procedures. Orthodontics for tomorrow will
      necessitate more concept and less mechanics.

PMID- 15952555
TI  - Mandibular third molars and late lower arch crowding--the evidence base.

PMID- 15952556
TI  - Individual patient (IP) appliances.

PMID- 15952557
TI  - Orthodontics' Conan Doyle.

PMID- 15952558
TI  - Braces as a "fashion statement" in the land of smiles.

PMID- 15952559
TI  - [Allergic rhinitis: an underestimated disease].

PMID- 15952560
TI  - [Importance of research of allergic rhinitis].

PMID- 15952561
TI  - [Diagnostic and treatment principle for allergic rhinitis and a recommended
      scheme].

PMID- 15952562
TI  - [Relationship between allergic factors and chronic sinusitis with or without
      nasal polyps].
AB  - OBJECTIVE: To explore the effects of allergic factors in chronic sinusitis and
      nasal polyps. METHOD: Eosinophil in nasal secretions and allergen skin test of
      1882 patients with chronic sinusitis and nasal polyps were examined before
      endoscopic sinus surgery. The occurrence ratios of allergic symptoms and
      syndromes were analyzed and compared with clinical stages of chronic sinusitis
      and nasal polyps. RESULTS: (1) Allergic symptoms (or syndromes) were presented in
      60.4% (1137 cases) of patients in different degrees, 25.3% (477 cases) patients
      suffered from allergic rhinitis, 2.1% (39 cases) patients had asthma; (2) The
      morbidities of allergic rhinitis and asthma, the positive rates of eosinophil and
      allergen skin test, the occurrence rates of allergic symptoms were rising with
      the clinical stages in type I and type II, especially in type II stage 3; (3)
      There were 42.2% (795 cases) positive patients in allergen skin test, among them,
      94% were sensitive to perennial allergens; (4) Allergic symptoms appeared in
      26.3% (495 cases) patients, among them, 99.8% attacked perennially; (5) Of all
      patients, there were 38.9% (732 cases) had been operated cases before, among them
      38.3% (280 cases) with allergy rhinitis. In chronic sinusitis with allergy
      rhinitis patients, 58.7% (477 cases) were suffered from operation. CONCLUSIONS:
      Allergic factors,especially perennial allergic rhinitis, are relative to clinical
      stages of chronic sinusitis and nasal polyps. Allergic rhinitis is an important
      factors in recurrence.

PMID- 15952563
TI  - [Expression and its significance of aquaporin 5 in rat nasal mucosa of
      experimental allergic rhinitis].
AB  - OBJECTIVE: To confirm the expression and distribution of aquaporin 5 (AQP5) in
      rat nasal mucosa of experimental allergic rhinitis and to investigate the
      relationship between AQP5 and allergic rhinitis. METHODS: Twenty-four healthy
      Wistar rats both male and female weighting 200-300 g were divided into two groups
      randomly, one was testing group (n = 12), the other was comparing group (n = 12).
      Generally sensitized rats in testing group were given repeated local booster
      sensitization into nasal cavity. Twelve normal rat nasal mucosa and twelve nasal
      mucosa from rat with allergic rhinitis were used. The distribution of AQP5 in
      normal rat nasal mucosa and nasal mucosa in rat with allergic rhinitis were
      observed by immunofluorescence technique. Furthermore, the expression of AQP5 in
      normal rat nasal mucosa and nasal mucosa from rat with allergic rhinitis were
      studied by immunohistochemical staining. RESULTS: Hematoxylin and eosin staining
      showed that there was obvious inflammation reaction, a large quantity of glands
      hyperplasia and acidophils soaked in nasal mucosa from rat with allergic
      rhinitis. (2) Both immunofluorescence technique and immunohistochemical staining
      showed that the distribution of AQP5 in normal rat nasal mucosa was in accordance
      with that in nasal mucosa from rat with allergic rhinitis on the whole. AQP5
      expressed mainly in the membrane and cytoplasm of the epithelium in the glands,
      ducts and cilia. (3) The statistical analysis of the immunohistochemical staining
      showed that the quantity of AQP5 in rat nasal mucosa with allergic rhinitis
      (156.37 +/- 1.93) was obviously higher than that in the normal rat nasal mucosa
      (178.52 +/- 1.94). There was statistical significance between the two groups (t =
      28.08, P < 0.01). CONCLUSIONS: The hypersecretion of glands has a close
      relationship with the high expression of AQP5 in allergic rhinitis.

PMID- 15952564
TI  - [Establishment of a modified intranasally ovalbumin induced animal model of
      allergic rhinitis].
AB  - OBJECTIVE: To observe the early and late symptomatic, pathological and
      immunological changes in an intranasal ovalbumin-induced animal model of allergic
      rhinitis in guinea pigs. METHODS: Guinea pigs were intranasally sensitized with
      ovalbumin absorbed on aluminum hydroxide and after 5 days' interval, they were
      challenged with 1% ovalbumin solution once every 3 days for total 11 times. Two
      control groups were studied in parallel, the positive treatment control group was
      treated with antihistamine and the negative control group was sham-sensitized and
      sham-challenged. Typical symptoms of allergic rhinitis, such as sneezing, nasal
      scratching, nasal blockage and rhinorrhea were evaluated. Passive cutaneous
      anaphylaxis reaction (PCA) was performed to measure the levels of IgG1 and IgE.
      Eosinophils infiltration and goblet cells in nasal mucosa were observed. In
      addition, the level of histamine and the number of total leukocytes and
      eosinophils in the nasal lavage fluid were also measured. RESULTS: In the model
      group, symptoms of sneezing, nasal scratching, nasal blockage and rhinorrhea were
      induced after ovalbumin challenge. The respiratory rate (RR), which reflected the
      resistance of upper airway, showed a biphasic change. In the PCA test, IgG1 and
      IgE levels increased after challenges. Eosinophil infiltration in nasal mucosa
      was more obvious in active groups in comparison to with the negative control
      group (P < 0.05 or < 0.01). The histamine, total leucocytes and eosinophils
      levels in nasal lavage fluid also showed higher in the model group (P < 0.05 or <
      0.01). The antihistamine treated animals were also induced out above changes but
      modest compared with the model group (P < 0.05 or < 0.01). The negative control
      showed few of above changes with significant difference (P < 0.05 or < 0.01).
      CONCLUSIONS: Our results implied that the modified animal model of allergic
      rhinitis was capable of showing satisfactory symptomatic and pathophysiological
      changes in allergic rhinitis. It showed a biphasic nasal blockage with shorter
      establishment duration. The model also had good treatment reaction to
      antihistamine. The animal model we introduced may be useful in the study of
      allergic rhinitis.

PMID- 15952565
TI  - [Summary of national academic meeting on allergic rhinitis and asthma].

PMID- 15952566
TI  - [Experimental study of cranial-cervical lymph return in rabbit].
AB  - OBJECTIVE: To study the cranial-cervical lymph return and pathway in rabbit in
      order to provide the experimental and theoretical basis for the study of
      intracranial metastasis of cervical tumor and extracranial metastasis of
      intracranial tumor. METHOD: The distribution and clearance of tracers were
      observed after microinjection of lymph developer labeled by 99mTc into cerebral
      cortex and deep cervical lymph nodes of rabbit. RESULTS: In the cerebral cortex
      microinjection with 99=Tc-labeled lymph developer group, the radioactivity were
      detected in Willis artery, deep cervical lymph nodes and venous blood. The
      radioactivity curve was the same in Willis artery and deep cervical lymph nodes.
      The peak in the artery blood was higher than that in venous blood. In the lymph
      nodes microinjection with 99mTc-labeled lymph developer cervical group, the
      radioactivity were detected in skull base dura mater, brain, cerebrospinal fluid
      and venous blood. The peak in skull base dura mater showed earlier than that in
      cerebrospinal fluid and brain. The peak in venous blood was the last, but the
      radioactivity in it was the highest. CONCLUSION: The cranial-cervical lymph
      return in rabbit is existent. Their pathway perhaps is Willis artery, skull base
      dura mater and cerebrospinal fluid circulation.

PMID- 15952567
TI  - [Role of microvessel density on human middle ear cholesteatoma].
AB  - OBJECTIVE: To explore the role of microvessel density in acquired middle ear
      cholesteatoma, to analyze it playing the possible role in proliferative ability
      of cholesteatoma epidermis. METHODS: The specimens from 15 cases acquired middle
      ear cholesteatoma patients having typical perforation in the posterior fold (the
      adjacent skin around perforation and the normal deep external ear skin) were
      examined by immunohistochemical ABC method. The microvessel density was analyzed
      by computer, and was compared with 20 cases non-cholesteatoma otitis media's the
      adjacent skin around perforation. RESULTS: Counts of microvessel and relative
      area of all microvessels per image in the adjacent skin around perforation were
      14.395 +/- 2.000 and (9.927 +/- 2.600)%, respectively. These were significantly
      higher than the normal deep external ear skin's with the average of 6.218 +/-
      0.949 and (5.076 +/- 0.807)% in 15 cases acquired middle ear cholesteatoma
      patients (P < 0.001). The adjacent skin around perforation of cholesteatoma was
      also significantly higher than non-cholesteatoma's with the average of 6.163 +/-
      1.051 and (5.785 +/- 1.428)% (P < 0.001). CONCLUSIONS: The adjacent skin around
      perforation in human middle ear cholesteatoma had a relatively hyperproliferative
      ability.

PMID- 15952569
TI  - [A case of cervical tumor-like foreign body originated from pyriform recess].

PMID- 15952568
TI  - [Long-term effect of stapes surgery on tympanosclerosis].
AB  - OBJECTIVE: To study the long-term effect of stapes surgery on tympanosclerosis
      and its influence factors. METHODS: The effect of stapes surgery on
      tympanosclerosis was retrospectively summed up in 119 patients (149 ears) in
      General Hospital of people's Liberation Army from April 1984 to March 2002. The
      Stata 7.0 software was used as a statistical tool. RESULTS: The average of
      hearing threshold (hearing level) of air conduction was (50.7 +/- 12.1) dB before
      operation, and the hearing loss was mostly on low frequency. Following-up the
      half-year post-operation, the average of hearing threshold of air conduction was
      (25.6 +/- 15.2) dB. The total successful rate of post-operation half year, 1
      year, 2 and 5 years were 50.3%, 45.8%, 41.3% and 34.5%, respectively. Comparing
      the different operation methods, stapedotomy (piston technique) owned the best
      effect on hearing recovery (62.5%), then was stapedectomy (43.1%), but the last
      one was stapediolysis (30.8%). There was significant difference effect among
      three different operation methods (P < 0.05). The average of hearing threshold of
      air conduction was steadily within the first five-years following-up (Ridit
      analysis, P > 0.05), but obviously increased more than 5 years after operation
      (Ridit analysis, P < 0.05). The influence factors to successful rate were the
      following-up time post-operation, pathological changes of stapes, operative
      methods, and complications during operation, respectively. CONCLUSION: Stapes
      surgery is the effective method to treat tympanosclerosis, but the long-term
      effect is not good enough as expectation. It is important to select proper
      operation methods for better hearing results.

PMID- 15952570
TI  - [Relationship between prognosis of nasal inverted papilloma and human
      papillomavirus types].
AB  - OBJECTIVE: To detected HPV human papillomavirus DNA and HPV types in NIP nasal
      inverted papilloma, to inquire into the infection of HPV in the pathogenesis of
      NIP, and the relationship of HPV with the prognosis of NIP. METHODS: Twenty-eight
      cases of NIP were divided into 3 groups: no recurrence group (group 1),
      recurrence group (group 2), squamous cell carcinoma (SCC) arising in NIP group
      (malignancy group, group 3). Ten cases of benign nasal polyps were used as
      control group. HPV-DNA types of 6, 11, 16, 18 and general type were detected by
      polymerase chain reaction (PCR). RESULTS: Total positive rate of HPV in NIP was
      75% (21/28). The positive rate of group 1 was 42% (5/12), all with single and low
      risk HPV type infection (4 with HPV6 and 1 with HPV11). Thirteen cases of
      recurrence and 3 cases of malignancy were discovered to have HPV-DNA, in group 2,
      the majority were HPV6 and HPV11, 4 cases with double infection;in group 3, the
      majority were HPV16 and HPV18, and 2 cases with double infection. CONCLUSIONS:
      The occurrence of NIP was related with HPV infection. To detected HPV and its
      subtypes can show the cases easily to have recurrence or malignant change. For
      the cases with HPV positive, double infection and infected with high risk types
      should be closely followed-up.

PMID- 15952571
TI  - [Examination expression of CD3 and CD69 in nasal polyps].
AB  - OBJECTIVE: To investigate the infiltration of T lymphocytes with CD3 expression
      as surface marker and the activation of T lymphocytes with CD69 expression as
      activation marker. METHODS: Nasal polyp tissue samples and peripheral blood were
      obtained from 21 patients. The normal inferior turbinate mucosa and peripheral
      blood were obtained as comparison. Flow cytometry was adopted to detect the
      expression of CD3 and CD69 of T lymphocytes. RESULTS: Nasal polyp tissue
      consisted of abundant T lymphocytes. Activation marker CD69 was expressed in T
      lymphocytes of nasal polyps (36.96 +/- 2.50)% and peripheral blood (4.66 +/-
      0.18)% from the same patient. The expression rates of CD69 after a short-term
      stimulation (5 h) in response to PDB were (59.88 +/- 2.59)% and (92.76 +/- 0.55)%
      respectively. While T lymphocytes was rarely detected in normal inferior
      turbinate and the expression of CD69 was low in peripheral blood from normal
      human but almost all T lymphocytes were activated after stimulation. CONCLUSIONS:
      There were generous of T lymphocytes infiltrating in nasal polyps. The expression
      of CD69 in T lymphocytes was abnormally high, which indicated that T lymphocytes
      infiltrating in nasal polyps were in activated state immunologically.

PMID- 15952572
TI  - [Relationship between expression of multidrug-resistant genes in nasopharyngeal
      carcinoma tissue and sensitivity to chemotherapy].
AB  - OBJECTIVE: To study the relationship between multidrug-resistant (MDR) expression
      in nasopharyngeal carcinoma (NPC) and its sensitivity to chemotherapy. METHODS:
      The specimens of 23 NPC cases were studied by immunohistochemistry with
      monoclonal antibody of P-glycoprotein (P-gp), multidrug resistance relation
      protein (MRP), lung-resistance related protein (LRP), topoisomerase II (Topo II),
      thymidylate synthase (TS), glutathione-S-transferase (GST-pi). Among them, 20
      specimens were taken from primary NPC lesion which were treated with two course
      of cisplatin (DDP) and 5-fluorouracil (5-FU), 3 specimens were taken from
      cervical lymph-node of recurrent NPC patients who were treated by radical
      dissection. RESULTS: Various MDR parameters were expressed differently in 22
      cases except for 1 clear cell carcinoma case. The difference was statistically
      significant (P < 0.05). However, there were no significant difference of MDR
      expression either among various carcinoma pathomorphology cell groups or among
      different clinical stage groups. Expression of LRP and TS were found in 10 and 14
      cases respectively and the chemotherapy responders rates were 20% (2/10) and
      28.5% (4/14) respectively. While the chemotherapy responders rates were 70%
      (7/10) and 5/6 in cases without expression. There was significant difference (P <
      0.001, and P < 0.05). CONCLUSION: The NPC patients with LRP and TS expression may
      be less sensitive to chemotherapy with DDP + 5-FU.

PMID- 15952573
TI  - [Thyroid cartilage flap reconstruction of cricoid in the management of subglottic
      carcinoma].
AB  - OBJECTIVE: To evaluate the effect of conservative surgical management on patients
      with subglottic cancer. METHODS: Nine cases with subglottic carcinoma were
      treated surgically from 1984 to 1999. There were T2N0 lesions in 2 cases, T3N0-1
      in 3 cases and T4N0-1 in 4 cases. All the cases underwent partial laryngectomy
      including partial cricoid resection. Variations of a pedicled thyroid cartilage
      flap were used for reconstruct the cricoid defect. The pedicle based muscle was
      thyrohyoid, sterno-thyroid or inferior constrictor. Unilateral neck dissection
      was performed on 7 cases and bilateral on two. RESULTS: The function of phonation
      were preserved in all cases. Eight of nine 8/9 were decanulated. Normal
      deglutition were achieved for all patients. The 3 and 5 year survival rates were
      8/9 and 6/9, respectively. CONCLUSION: Pedicled thyroid cartilage flap is
      appropriate for reconstruction of the cricoid defect in the conservative surgery
      of selected subglottic carcinoma.

PMID- 15952574
TI  - [Preservation of laryngeal function in surgical treatment of pyriform sinus
      carcinoma].
AB  - OBJECTIVE: To explore the feasibility and the related surgical techniques of
      laryngeal function preservation in surgical treatment of pyriform sinus cancer.
      METHODS: Two hundred and thirty cases (stage I, 6; stage II, 10; stage III, 91;
      stage IV, 123) with pyriform sinus cancer were treated surgically from 1978 to
      1996 in the Department of Otorhinolaryngology of Qilu Hospital of Shandong
      University. The methods of removing tumor and repairing surgical defects were
      depended on the extension of lesions. The laryngeal and pharyngeal functions were
      rebuilt by normal tissue preserved with lesions entirely removed. One hundred and
      fifty-eight cases were surgically treated with laryngeal functions preserved and
      72 cases total laryngectomy. The most of the cases received postoperative
      radiotherapy. RESULTS: The overall 3 and 5 year survival rates were 67.4%
      (155/230) and 48.3% (111/230) respectively. For stage I, the survival rate was
      5/6; stage 11, 70.0% (7/10); stage III, 57.1% (52/91) and stage IV, 38.2%
      (47/123); the 3 and 5 year survival rates in functionally preserved group were
      67.7% (107/158) and 50.0% (79/158), while in none functional group were 66.7%
      (48/72) and 43.1% (31/72), respectively. 75.3% (119/158) patients have laryngeal
      functions (voice,respiration and deglutition) completely restored and 24.7% (39/
      158) partially restored(voice and deglutition). CONCLUSIONS: The preservative
      surgery is feasible for the selected pyriform sinus cancer cases. Choosing and
      following optimum surgical methods is a prerequisite for improving the quality of
      life of the cases.

PMID- 15952575
TI  - [Experience on the diagnosis and treatment for pharyngeal foreign bodies].

PMID- 15952576
TI  - [Three cases of congenital middle ear malformation and cholesteatoma].

PMID- 15952577
TI  - [Three cases of trigeminal neuralgia caused by basilar artery twist].

PMID- 15952578
TI  - [A cases of nasal metastases from clear cell carcinoma of the kidney].

PMID- 15952579
TI  - [Endoscopic nasal surgery in the treatment of nasopharyngeal angiofibroma].

PMID- 15952580
TI  - [Treatment of chronic dacryocystitis by dacryocystorhinostomy with microwave
      under nasal endoscope].

PMID- 15952581
TI  - [New method of intraoral measure in obstructive sleep apnea-hypopnea syndrome].

PMID- 15952582
TI  - [A case of fibrolipoma in retropharyngeal space].

PMID- 15952583
TI  - [A suggestion for revision of the staging of chronic sinusitis and nasal
      polyposis].

PMID- 15952584
TI  - [Advances in the treatment of allergic rhinitis].

PMID- 15952585
TI  - [Staphylococcal superantigens and chronic inflammation of nasal mucosa].

PMID- 15952586
TI  - [Fungal rhinosinusitis].

PMID- 15952587
TI  - [Application of RNAi to cancer therapy].

PMID- 15952588
TI  - [Progress in renal drug targeting].

PMID- 15952589
TI  - [Reversal of multidrug resistance in drug-resistant cell line EAC/ADR by
      cepharanthine hydrochloride and its mechanism].
AB  - AIM: To investigate the correlation between reversal effect of cepharanthine
      hydrochloride (CH) on multidrug resistance (MDR) in drug-resistant cell line
      EAC/ADR and the nuclear transcription factor-KB (NF-KB). METHODS: Cytotoxicity
      was determined by the tetrazolium (MTT) assay in vitro. An EAC/ADR cell homograft
      model was established to investigate the effect of CH on reversing MDR in vivo.
      The constitutive activity and activation of NF-KB by drugs were measured by Dot
      Enzyme-linked Immune Sorbent Assay (Dot-ELISA). RESULTS: CH was shown to
      potentiate the cytotoxicity of ADR, a 13- fold reversal effect of resistance was
      achieved in vitro. In mice bearing EAC/ADR cell homografts, CH was found to
      prolong the survival time of animals bearing tumor. Increase in life span over
      control was 75. 37%. In addition, the constitutive activity of NF-KB and
      activation of NF-KB by chemotherapy were lowered by CH. CONCLUSION: The findings
      suggest that CH is able to reverse drug resistance and its mechanism may be
      related to suppressing the constitutive activity and activation of NF-KB by
      drugs.

PMID- 15952590
TI  - [Effects of enalapril on plasma Ang II level and the expression of AT1 in blood
      vessel and kidney of type 2 diabetic rats].
AB  - AIM: To study the plasma angiotensin II (Ang II) levels and the expressions of
      angiotensin II1 receptor (AT1) in blood vessels and kidneys in diabetic and high
      fat diet rats, and the effects of enalapril on plasma Ang II levels and the
      expressions of AT1 in blood vessels and kidneys in diabetic rats. METHODS: The
      plasma Ang II level was assayed with 125I-Ang II radioimmunoassay, and the
      expression of AT1 in blood vessel and kidney was analyzed with
      immunohistochemical technique. RESULTS: The plasma Ang II level was significantly
      higher in type 2 diabetic rats (241 +/- 49) pg x mL(-1) than that in the control
      (71 +/- 22) pg x mL , high fat diet group (151 +/- 29) pg x mL(-1) (P < 0.01) ,
      and enalapril-treated groups (136 +/- 25) pg x mL(-1) (P < 0.05). The plasma Ang
      II levels in high fat diet and in enalapril-treated groups were also
      significantly higher than that in control group ( P < 0.01 ). With
      immunohistochemical technique, it was found that the expression of AT1 in
      endothelial cells of blood vessels, vascular smooth muscle cells, and kidneys in
      diabetic group increased. The expression of AT1 in endothelial cells of blood
      vessels, vascular smooth muscle cells, and kidney in enalapril-treated group was
      similar to that in control group. CONCLUSION: The plasma Ang II levels and the
      expression of AT1 in type 2 diabetic and high fat diet rats increased. Enalapril
      was shown to decrease the plasma Ang II level and downregulate the expression of
      AT1 in blood vessels and kidneys in type 2 diabetic rats.

PMID- 15952591
TI  - Effects of gingko biloba extract on glutamate-induced [Ca2+]i changes in cultured
      cortical astrocytes after hypoxia/reoxygenation, H2O2 or L-glutamate injury.
AB  - AIM: To investigate glutamate-induced [Ca2+]i changes in cultured rat neonatal
      cortical astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L
      glutamate injury. In the meantime, the effects of Gingko biloba extract (GbE)
      were examined. METHODS: [Ca2+]i changes in astrocytes were monitored by laser
      scanning confocal microscopy with the Ca2+ sensitive fluorescent probe fluo-3.
      RESULTS: After astrocytes were impaired by hypoxia/reoxygenation, H2O2 (50
      micromol x L(-1)) or L-glutamate (0.25 mmol x L(-)), the exogenous glutamate (27
      micromol x L(-1)) could not induce increase of [Ca2+]i, but decrease by (3.3 +/-
      1.6)%, (81 +/- 11)% and (81 +/- 7)%, respectively. Pretreatment with GbE (10 mg x
      L(-1)) could not improve injured astrocytic glutamate response. But after
      pretreatment with GbE (100 mg x L(-1)), glutamate-induced [Ca2+]i elevation of
      astrocytes after hypoxia/reoxygenation, H2O2 or high concentration of L-glutamate
      injury were (135 +/- 98)%, (117 +/- 93)% and (89 +/- 36)%, respectively.
      Nimodipine (1.6 mg x L(-1)) could also reverse the abnormal response of
      astrocytes after different injury. CONCLUSION: Hypoxia/reoxygenation, H2O2 and
      high concentration of L-glutamate impaired astrocytes' response to exogenous L
      glutamate, and then bidirectional communication between astrocytes and neurons
      could not take place. GbE could improve the abnormal responses and maintain the
      normal function of astroglical network. These effects support that GbE has
      potential beneficial actions against brain injury.

PMID- 15952592
TI  - Protective effects of hydroxyethylpuerarin on cultured bovine cerebral
      microvascular endothelial cells damaged by hydrogen peroxide.
AB  - AIM: To observe the damages induced by hydrogen peroxide in cultured bovine
      cerebral microvascular endothelial cells (BCMEC) and evaluate the protective
      effects of hydroxyethylpuerarin on hydrogen peroxide-injured BCMEC. METHODS:
      BCMEC were cultured and transferred into modified Eagle medium (MEM). The
      viability of cells was detected by MTT assay. Cell injury was determined by
      lactate dehydrogenase (LDH) activity in the extracellular medium. Flow cytometry
      was employed to observe the occurrence of apoptosis. Morphologic changes of cells
      were visualized under phase contrast and electron microscopes. RESULTS: Hydrogen
      peroxide (200 micromol x L(-1) for 4 hours) inhibited the viability of cultured
      BCMEC and stimulated LDH release. Hydrogen peroxide (100 micromol x L(-1) for 4
      hours) induced the occurrence of apoptosis. Hydroxyethylpuerarin was shown to
      increase the survival rate and decrease the activity of LDH of BCMEC damaged by
      hydrogen peroxide. Hydroxyethylpuerarin was also found to protect BCMEC against
      apoptosis induced by hydrogen peroxide. CONCLUSION: Hydrogen peroxide induces
      BCMEC injury either by apoptosis or through necrosis. Hydroxyethylpuerarin
      protects BCMEC against hydrogen peroxide-induced injury in a concentration
      dependent manner. Its antioxidant effects might be involved as the mechanism
      protection.

PMID- 15952593
TI  - [Ginsenoside Rbl attenuates beta-amyloid peptide25-35 -induced tau
      hyperphosphorylation in cortical neurons].
AB  - AIM: To explore the effect and the possible mechanism of ginsenoside Rb1 on beta
      amyloid peptide (beta-AP)(25-35) -induced tau protein hyperphosphorylation in
      cortical neurons. METHODS: Western blotting and immunocytochemical staining were
      used to detect tau phosphorylation level, total tau and glycogen synthase kinase
      3beta (GSK-3beta) in cortical neurons. RESULTS: After exposure to beta-AP(25-35)
      (20 micromol x L(-1)) for 12 h, the levels of tau protein phosphorylation in the
      sites of Ser 396, Ser 199/202, Thr 231 and total tau were raised. Meanwhile, the
      expression of GSK-3beta also increased. Pretreatment with ginsenoside Rbl or
      lithium chloride, a specific inhibitor of GSK-3beta, markedly reduced beta-AP(25
      35)-induced tau hyperphosphorylation and the expression of GSK-3beta. CONCLUSION:
      Ginsenoside Rb1 can attenuate beta AP(25-35)-induced tau protein
      hyperphosphorylation in cortical neurons by inhibiting the expression of GSK
      3beta.

PMID- 15952594
TI  - [Effect of epigallocatechingallate on acute lung injury induced by oleic acid in
      mice].
AB  - AIM: To investigate the effect of epigallocatechingallate (EGCG) on acute lung
      injury induced by oleic acid in mice and the possible mechanism. METHODS: Acute
      lung injury was induced by oleic acid in mice. Light microscopy and electron
      microscopy were used to examine histological changes and lung index as well as
      wet to dry weight ratio was calculated. Serum TNF-a level was measured by enzyme
      linked immunosorbent assay (ELISA) and the phosphorylation of p38 MAPK was
      determined by Western blotting. RESULTS: Pretreatment of EGCG significantly
      alleviated oleic acid induced lung injury accompanied by reduction of lung index
      and wet to dry weight ratio, decreased of TNF-a level in serum and inhibition of
      phosphorylation of p38 MAPK. CONCLUSION: EGCG showed beneficial effect on acute
      lung injury induced by oleic acid in mice. The ultimate reduction of TNF-alpha in
      serum caused by inhibition of phosphorylated p38 MAPK is involved in the
      mechanism of action of EGCG.

PMID- 15952595
TI  - [Location and relative quantity of coumarins in the stem of Dendrobium
      thyrsiflorum].
AB  - AIM: To determine the location and relative quantity of coumarins in the stem of
      Dendrobium thyrsiflorum Rchb. f. , and to provide a scientific basis for
      evaluating and utilizing the famous medicinal plant. METHODS: The stems of one,
      two and three years old, separately, were collected in February. Location and
      relative quantity of coumarins in the top, middle and basal parts of each stem
      sample were determined by using laser scanning confocal microscopy (LSCM). ANOVA
      and Tukey's test were employed in the statistical analysis. RESULTS: The
      coumarins located mainly in vascular bundles, especially on the walls of the
      outer fiber cells. There was significant difference or great significant
      difference exist in every part of the stem from different ages. The values of
      significant difference were as follows: basal part P = 0.004 (< 0.01); middle
      part P = 0.009 (< 0.01); top part P = 0.036( < 0.05). CONCLUSION: Two years old
      stem could be the best choice when collecting Dendrobium thyrsiflorum in
      Feburary.

PMID- 15952596
TI  - Synthesis and antitumor activity of A-ring modified hexacyclic analogues of
      camptothecin.
AB  - AIM: To improve the biological activity of A-ring modified analogues of
      camptothecin. METHODS: A-ring modified camptothecins were synthesized from 10
      hydroxycamptothecin or 7-ethyl-10-hydroxycamptothecin (SN-38) in three or four
      steps. Their cytotoxicity was evaluated using MTY assay, and their in vivo
      antitumnor activity against mouse liver cancer H22 was tested. Results Five
      hexacyclic camptothecins (6a, 6b, 6c, 7a and 7b) are target compounds, and ten
      camptothecin derivatives are new compounds. CONCLUSION: The modification of a 1,4
      oxazine-2-one ring fused with positions 9 and 10 of A-ring will reduce the
      antitumor activity of camptothecins.

PMID- 15952597
TI  - [Isolation and structure identification of chemical constituents from Anabasis
      brevifolia].
AB  - AIM: To study the chemical consitituents of the n-butanol-extracts of Anabasis
      salsa and Various chromatographic techniques were used to the chloroform-extract
      of Anabasis brevifolia. METHODS: separate and purify the constituents. Their
      physico-chemical properties and spectral data were used to elucidate their
      structures. RESULTS: Five compounds were isolated and identified as 2-O-beta-D
      glucopyranosyloxy-4,6-dimethoxy phenylenthanone (1), 2-O-(2)-beta-D
      glucopyranosyloxy-4, 6-dimethoxy phenylenthanone (2), 3-methyl-but-2-enoic acid
      [2-(4-methoxy phenyl)-ethyl]-amide (3), 5,6,7,2'-tetramethoxy isoflavonoid (4),
      2'-hydroxy-5,6,7-trimethoxyisoflavonoid (5). CONCLUSION: Compounds 2, 3, and 5
      are new compounds. And the others were isolated from Anabasis L. for the first
      time.

PMID- 15952598
TI  - [Chemical constituents of the rhizome of Matteuccia struthiopteris].
AB  - AIM: To study the chemical constituents of the rhizome of Matteuccia
      struthiopteris (L.) The constituents were separated and purified by column
      chromatography with normal Todaro. METHODS: phase silica gel and Sephadex LH-20.
      Their structures were identified on the basis of physical and spectral data (MS,
      NMR, HMBC and HMQC). RESULTS: Four compounds were isolated and identified as 1-O
      beta-D-gl ucopyranosyl-(2S,3R,4E, 8Z) -2-N-(2'-hydroxydocosanoyl) eicosasphinga
      4,8-dienine (1), 1-O-beta-D-galactosyl-(6-->1)-alpha-D-galactosyl-2,3-O
      dihexadecanoyl-glycerol (2), succinic acid (3), D-mannitol (4). CONCLUSION:
      Compounds 1 and 2 are new compounds. Compounds 3 and 4 were isolated from this
      plant for the first time.

PMID- 15952599
TI  - Isolation and structure determination of cypritibetquinone A and B, two new
      phenanthraquinones from Cypripedium tibeticum.
AB  - AIM: To study the chemical constituents of Cypripedium tibeticum. METHODS:
      Compounds were isolated by repeated silica gel chromatography and purified on
      Sephadex LH-20 and structures were determined by spectral analysis. RESULTS:
      Cypritibetquinones A and B were isolated from the ethyl acetate residue and their
      structures were determined as 7-hydroxy-2-methoxy-1 4-phenanthraquinone (1) and 7
      hydroxy-2, 10-dimethoxy-l1 4-phenanthraquinone (2), respectively, by extensive
      spectral analyses. CONCLUSION: Cypritibetquinones A and B are two new
      phenanthraquinones.

PMID- 15952600
TI  - [Distribution and pharmacokinetics of 20S-ginsenoside Rg3 eyeointment in rabbit
      eye].
AB  - AIM: To determine 20S-ginsenoside Rg3 in various tissues of rabbit eye and
      evaluate pharmacokinetics following its topical application. METHODS: 45 rabbits
      were divided into 9 groups. Aqueous humor, cornea and iris-ciliary body were
      collected at 0.017, 0.033, 0.083, 0.167, 0.5, 1.0, 1.5, 2.0 and 3.0 h following
      topically applying 1% 20S-ginsenoside Rg3 eyeointment and the concentrations in
      eye tissues were measured by HPLC. RESULTS: The pharmacokinetics of 20S
      ginsenoside Rg3 in rabbit eye were described by one-compartment model. The peak
      times in aqueous humor, cornea and iris-ciliary body were 0.42, 0.16 and 0.19 h,
      and T(1/2) were 0.1, 0.9 and 0.8 h respectively. CONCLUSION: The method of
      determining 20S-ginsenoside Rg3 in rabbit eyes was established. The
      pharmacokinetics parameters were determined.

PMID- 15952601
TI  - [Determination of unconjugated neurosteroids in rat brain regions by liquid
      chromatography-negative atmospheric pressure ionization mass spectrometry].
AB  - AIM: To simultaneously determine three unconjugated neurosteroids,
      dehydroepiandrosterone (DHEA) , pregnenolone (PREG), allopregnenolone (AP), from
      several brain regions of the rat. METHODS: Neurosteroids were isolated separately
      in a two steps procedure by using ethyl acetate-n-hexane (90:10) as the first
      step to extract the unconjugated steroids, then the steroid fractions were
      further purified by SPE. All steroids were derivatized with 2-nitro-4
      trifluoromethylphenylhydrazine (2-NFPH) and analyzed by HPLC-MS ( APCI) using
      selected-ion monitoring. Methyltestosterone was chosen as the internal standard.
      Results The linear calibration curve of DHEA was obtained in the concentration
      range of 0.030-2.00 microg x L(-1). The linear calibration curves of PREG and AP
      were obtained in the concentration range of 0.025-2.00 microg x L(-1). The
      concentrations of DHEA, PREG and AP in male rat brain regions were (0.70 +/-
      0.23), (4.8 +/- 1.9), (1.1 +/- 0.6) ng x g(-1) for frontal cortex, (0.57 +/-
      0.28), (6 +/- 3), (0.5 +/- 0.3) ng x g(-1) for hippocampus, (1.5 +/- 1.0), (9 +/-
      5), (1.4 +/- 0.9) ng x g(-1) for amygdale, (0.52 +/- 0.14), (7.7 +/- 2.8), (0.5
      +/- 0.6) ng x g(-1) for striatum, (2.9 +/- 1.6), (18 +/- 9), (1.6 +/- 1.3) ng x
      g(-1) for nucleus accumbens, (4.0 +/- 2.0), (27 +/- 12), (0.8 +/- 0.5) ng x g(-1)
      for pituitary gland, (1.7 +/- 1.2), ( 16 +/- 10), and (0. 8 +/- 0.7) ng x g(-1)
      for hypothalamus, respectively. CONCLUSION: Good linearity and accuracy were
      observed for each steroid. The procedure was suitable for measuring
      concentrations of the unconjugated steroids in rat brain simultaneously.

PMID- 15952602
TI  - Preparation of enteric microsphere of oleanolic acid dihemiphthalate sodium by
      salting-out action using spherical crystallization technique.
AB  - AIM: Enteric microspheres were prepared to prevent the interaction of drug with
      gastric acid and to improve its bioavailability. METHODS: The enteric
      microspheres with a matrix structure were successfully produced using a spherical
      crystallization technique. Hydroxypropyl methylcellulose phthalate (HP-55), an
      enteric material, was coprecipitated with the drug by salting-out effect during
      the preparation process. A mixture of water and ethanol was chosen as a good
      solvent and dichloromethane was used as a bridging agent while 0.1 mol x L(-1)
      sodium chloride solution was selected as a poor solvent. RESULTS: It is the first
      time to prepare microspheres by making the water-soluble drug and water-insoluble
      excipient coprecipitated. In vivo test demonstrated that the drug absorption from
      the enteric oleanolic acid dihemiphthalate sodium (OADHPS) microspheres was
      significantly prolonged compared to that with OADHPS powder after a lag-time.
      Furthermore, the drug bioavailability was 181.6% greater than that with the
      OADHPS powder. CONCLUSION: The microspheres of water soluble drug could be
      prepared by using water phase replacing organic phase as poor solvent which
      decrease the quantity of organic solvent and benefit the environment prevention.

PMID- 15952603
TI  - [Preparation of lung targeting azithromycin liposomes and its tissue distribution
      in mice].
AB  - AIM: To prepare lung targeting azithromycin cationic liposomes and to observe its
      tissue distribution in mice. METHODS: The azithromycin cationic liposomes were
      prepared by thin film method with freeze-thawing steps. HPLC method was
      established and validated for the determination of azithromycin in tissues of
      mice. RESULTS: The particle size of the liposomes was 6.582 microm with zeta
      potential of +19.5 mV. The entrapment efficiency was more than 75%. The liposomes
      was stable in 6 months stored at 4 degrees C. The release in vitro was
      characterized by Higuchi equation. Azithromycin liposomes and free azithromycin
      solution were injected intravenously at a dose of 80 mg x kg(-1) to mice.
      Compared with solution, liposomes were characterized by slower clearance,
      increased half-life and the AUC increased by 7.4 fold in lung. CONCLUSION: Thin
      film method with freeze-thawing steps could increase the entrapment efficiency
      and increase the particle size of azithromycin liposomes. After modification of
      lipid membrane with stearylamine, the cationic liposomes were prepared. The
      azithromycin concentration and AUC increased in lung after iv administration to
      mice of the cationic liposomes. This offered a good information for preparing
      liposomes targeting on the lung.

PMID- 15952604
TI  - [Evaluation of correlation between gelatin crosslinking indicators and influence
      factors].
AB  - AIM: To evaluate the correlation between the swelling equilibrium quantity (Seq),
      dissolution rate and amino group content which were used to estimate the degree
      of gelatin crosslinking, and the factors which influence the crosslinking, and to
      investigate the crosslinking mechanism of delayed dissolution of soft capsules.
      METHODS: The swelling equilibrium quantity, dissolution rate and amino group
      content of formaldehyde-crosslinked capsule shells were determined. Gelatin
      structure was analyzed by means of DSC. RESULTS: A good lineal relativity was
      found between the swelling equilibrium quantity, dissolution rate and amino group
      content (r = 0.9953-0.9985). The Seq of capsule shells was influenced by high
      temperature, lighting and some additives. Glycine and sodium pyrosulfite might
      retard the decrease of Seq of capsule shells. CONCLUSION: The swelling
      equilibrium quantity, dissolution rate and amino group content exhibited the same
      rule in gelatin crosslinking extent. High temperature, lighting and some
      additives might induce gelatin crosslinking. Antioxidant such as glycine and
      sodium pyrosulfite might retard the crosslinking.

PMID- 15952605
TI  - Simultaneous determination of eight main flavonoids in Flos lonicerae by high
      performance liquid chromatography.

PMID- 15952606
TI  - Collection and preparation of sensor network data to support modeling and
      analysis of outpatient clinics.
AB  - Simulation studies of outpatient clinics often involve significant data
      collection challenges. We describe an approach for data collection using sensor
      networks which facilitates the collection of a large volume of very detailed
      patient flow data through healthcare clinics. Such data requires extensive
      preprocessing before it is ready for analysis. We present a general data
      preparation framework for sensor network generated data with particular emphasis
      on the creation and analysis of patient path strings. Several examples of the
      analysis of sensor network data are also presented. Our approach has been used in
      two large outpatient clinics in the United States.

PMID- 15952607
TI  - Mathematical models for the early detection and treatment of colorectal cancer.
AB  - Colorectal cancer is a major cause of death for men and women in the Western
      world. When the cancer is detected through an awareness of the symptoms by a
      patient, typically it is at an advanced stage. It is possible to detect cancer at
      an early stage through screening and the marked differences in survival for early
      and late stages provide the incentive for the primary prevention or early
      detection of colorectal cancer. This paper considers mathematical models for
      colorectal cancer screening together with models for the treatment of patients.
      Illustrative results demonstrate that detailed attention to the processes
      involved in diseases, interventions and treatment enable us to combine data and
      expert knowledge from various sources. Thus a detailed operational model is a
      very useful tool in helping to make decisions about screening at national and
      local levels.

PMID- 15952608
TI  - Hospital cost flexibility in the presence of many outputs: a public-private
      comparison.
AB  - This paper develops flexibility measures in the context of a multi-firm output
      based on a generalized average cost function. We then apply this methodology to
      assess and compare the relative flexibility of hospital services in Quebec and
      California based on two very complete data sets. Results indicate that there is
      no clear distinction between private and public institutions and that there is no
      clear distinction between Quebec and California hospitals. However, there are
      clear differences in flexibility among different outputs. This last result
      suggests that there are bottlenecks in the health care system and calls for a
      targeted approach on the part of hospital administrators, whether public or
      private, in Quebec or California.

PMID- 15952609
TI  - Quantifying effect of a hospital's caseload for a surgical specialty on that of
      another hospital using multi-attribute market segments.
AB  - Inpatient and outpatient data were used to create market segments consisting of
      hierarchical combinations of surgical procedure, then type of payer, and then
      location of patients' residences. The competitive effect of one hospital's
      caseload for a given surgical specialty on the caseload of another hospital was
      determined from the numbers of patients in each segment. Earlier methods for
      estimating surgical competition that ignored market segments over-estimated the
      competitive effects of one hospital on another. Thus, results differed from those
      obtained previously for all types of hospital admissions. When actual market
      segments with homogeneous groups of patients are used, competitive effects of
      hospitals in the same market area are far less than expected.

PMID- 15952610
TI  - Assessing and using the multiple correlated components of the burden of disease
      in decision-making in health care.
AB  - In medical decision-making, we must (a) establish the patient's prognosis, and
      (b) identify the therapeutic strategy that will best improve that prognosis. The
      prognosis is the projected progression over time of the cumulative probability of
      (a) mortality, (b) morbidity, (c) disability, (d) psychological distress, and (e)
      resource use. Our modeling employs parametric representations and multivariate
      analysis to produce the predicted individual and joint probabilities of any range
      of each measure and of combinations of the measures. The predicted probabilities
      are consistent with their observed values. We have demonstrated, we believe, the
      feasibility of analyzing and predicting the burden of disease as a means to
      support decision-making at the bedside and the policy level.

PMID- 15952611
TI  - The cost efficiency and clinical quality of institutional long-term care for the
      elderly.
AB  - This study applied the stochastic frontier cost function with inefficiency
      effects to estimate the association between quality of care and cost efficiency
      in institutional long-term care wards for the elderly in Finland. We used several
      clinical quality indicators for indicating adverse care processes and outcomes,
      based on the Resident Assessment Instrument (RAI)/Minimum Data Set (MDS). Average
      cost inefficiency among the wards was 22%. We found an association between the
      clinical quality indicators and cost inefficiency. Higher prevalence of pressure
      ulcers was associated with higher costs, whereas the higher prevalence of use of
      depressants and hypnotics increased inefficiency.

PMID- 15952612
TI  - Ranking the 'balance' of state long-term care systems: a comparative exposition
      of the SMARTER and CaRBS Techniques.
AB  - The use of attribute sets to rank units of health provision (e.g., states,
      organizations) against policy goals is an essential task within decision-making
      and analysis. This paper elucidates and compares two techniques, SMARTER (Simple
      Multiattribute Rating Technique Exploiting Ranks) and CaRBS (Classification and
      Ranking Belief Simplex), within an expositional ranking of US states' long-term
      care (LTC) systems against the policy goal of providing a balance between
      (traditionally dominant) institutional care, and alternative home and community
      based services (HCBS). While the (more established) SMARTER technique is used
      primarily for comparative purposes, greater emphasis is placed on elucidating
      CaRBS which is based on the Dempster-Shafer theory of evidence. It is shown that
      CaRBS offers four appealing features for health policy analysis: (1) the capacity
      to rank using either of two confidence measures (DST-related belief and
      plausibility values), (2) a systematic approach to managing missing data, (3) the
      production of stable rankings, and (4) the simplex plot method of data
      representation. In addition to discussing the LTC policy implications of the
      study findings, the issues of rank order stability and the management of missing
      data are discussed with respect to the two techniques employed.

PMID- 15952614
TI  - Hospital prevails in medical staff privileges dispute. Weinberg v. Cedars-Sinai
      Medical Center.

PMID- 15952613
TI  - Mathematical modeling and pharmaceutical pricing: analyses used to inform in
      licensing and developmental go/No-Go decisions.
AB  - In the face of significant real healthcare cost inflation, pressured budgets, and
      ongoing launches of myriad technology of uncertain value, payers have formalized
      new valuation techniques that represent a barrier to entry for drugs. Cost
      effectiveness analysis predominates among these methods, which involves
      differencing a new technological intervention's marginal costs and benefits with
      a comparator's, and comparing the resulting ratio to a payer's willingness-to-pay
      threshold. In this paper we describe how firms are able to model the feasible
      range of future product prices when making in-licensing and developmental Go/No
      Go decisions by considering payers' use of the cost-effectiveness method. We
      illustrate this analytic method with a simple deterministic example and then
      incorporate stochastic assumptions using both analytic and simulation methods.
      Using this strategic approach, firms may reduce product development and in
      licensing risk.

PMID- 15952615
TI  - [The distribution of fimA genotype of Porphyromonas gingivalis in chronic
      periodontitis patients].
AB  - OBJECTIVE: To investigate the distribution of fimA genotype of P. gingivalis in
      chronic periodontitis patients. METHODS: Subgingival plaque samples were
      collected from 101 chronic periodontitis patients. P. gingivalis was detected by
      both culture method and P. gingivalis 16S rRNA PCR. fimA type-specific primer
      were designed, and the distribution of fimA genotype of P. gingivalis in
      periodontitis patients were detected by PCR. RESULTS: The detective ratio of P.
      gingivalis was 88.1%. Among them, a single fimA genotype was detected in most
      subgingival plaque samples (65.1%), and the distribution of five fimA genotypes
      among P. gingivalis positive patients was as follows: type I, 24.7%; type II,
      43.8%; type III, 15.7%; type IV, 40.4%; type V, 3.4%; respectively. CONCLUSION:
      P. gingivalis with various fimA genotypes were present in subgingival plaque
      samples from chronic periodontitis patients, and P. gingivalis with type II fimA
      and IV fimA were more predominant in chronic periodontitis patients, and they may
      be associated with the development of periodontitis.

PMID- 15952616
TI  - [Influence of dexamethasone on fusion of embryonic palatal medial edge epithelium
      in mouse palatal shelves in vitro].
AB  - OBJECTIVE: To study the effect of dexamethasone on the differentiation and
      proliferation of type A mouse palatal medial edge epithelial cells when there is
      type A mouse embryonic palatal mesenchymal cells. METHODS: The mouse palatal
      shelves were harvested from a female mouse of gestation day 14 by microsurgical
      dissection and cultured in vitro. The differentiation was investigated through
      microscope and transmission electron microscope under condition of the palatal
      shelves fusion. RESULTS: Dexamethasone promoted the palatal medial edge
      epithelium differentiated into squamause epithelium and affected normal
      development and obstructed the fusion of mouse palatal shelves. CONCLUSION: The
      results of histological observation indicate that dexamethasone promotes the
      proliferation of palatal meseuchymal cells and inhibits the normal
      differentiation of palatal medial edge epithelial cells, which results in cleft
      palate.

PMID- 15952618
TI  - [The changes of cytoskeleton F-actin in rat bone marrow mesenchymal stem cells
      and calvarial osteoblasts under mechanical strain].
AB  - OBJECTIVE: To explore the response of rat bone marrow mesenchymal stem cells
      (MSCs and calvarial osteoblasts to mechanical strain and the consequent changes
      of cytoskeleton F-actin. METHODS: Bone marrow MSCs and calvarial osteoblasts were
      isolated from SD rats and cultured in vitro. Mechanical stretch was performed on
      passage 3 cells at 2 000 microepsilon for 0, 2, 6 and 12 hours using four-point
      bending system. The response of cells and the distribution of F-actin were
      observed using fluorescent staining under laser scanning confocal microscope and
      the morphological parameters were quantified using image analysis software
      Laserpix. RESULTS: Under mechanical stretch, the fluorescent staining decreased
      obviously at both MSCs and osteoblasts, and F-actin filaments were rearranged and
      became tenuous, thinner, and abnormally distributed. The outline of nucleus
      became unclear and apoptotic changes were observed at some of both cells.
      Cellular size decreased more significantly in MSCs than in osteoblasts. Quantity
      analysis showed that total area of cells, total fluorescent density and green
      fluorescent density (F-actin) were all significantly decreased in MSCs (P < 0.05
      or P < 0.01), and total fluorescent density, green fluorescent density and red
      fluorescent density (nuclei) did also in osteoblasts (P < 0.05 or P < 0.01).
      CONCLUSION: Mechanical stretch caused extensive response on both MSCs and
      osteoblasts which led to the rearrangement of F-actin filament and apoptosis in
      some of these cells. MSCs were more sensitive to mechanical strain than
      osteoblasts.

PMID- 15952617
TI  - [The study of cell biocompatibility of new pattern biphasic calcium phosphate
      nanocomposite in vitro].
AB  - OBJECTIVE: To study the cell biocompatibility of porous biphasic calcium
      phosphate nanocomposite in vitro. METHODS: Bone marrow mesenchymal cell (BMSCs)
      obtained from SD rat bone marrow were in vitro induced and proliferated. Afler
      their osteoblast phenotypes were verified, BMSCs were seeded onto prepared porous
      biphasic calcium phosphate nanocomposite (Experiment group) and common porous
      hydroxyapatite (Control group). The cell adhesion was evaluated by scanning
      electron microscope. Synthesis of alkaline phosphatase enzyme (ALP) and
      osteocalcin were detected and cell cycle was detected by flow cytometry. RESULTS:
      BMSCs could fully attach to and extend on the material in experiment and control
      group, Moreover, experiment group were superior to control group in adhesion,
      proliferative abilities and osteogenic activity. CONCLUSION: BMSCs can
      differentiate to osteoblast phenotype; the porous biphasic calcium phosphate
      nanocomposite as bone tissue engineering scaffold has good cell biocompatibility.

PMID- 15952619
TI  - [The effect of matrix metalloproteinase-1 on root surface dentin matrix: a
      scanning electron microscope observation].
AB  - OBJECTIVE: To observe the effect of matrix metalloproteinase-1 (MMP-1) from human
      host on degradation of dentin organic matrix of root dentin. METHODS: The freshly
      extracted caries-free impacted teeth were selected. Teeth were cut transversely
      under the enamel-cementum junction into dentin sections with a thickness of about
      5 mm. Then all sections with removal of cementum, pulp and predentin were
      randomly divided into four groups. In the first group, dentin sections were
      demineralized with acid solution for 21 days, and then incubated with MMP-1
      solution for 7 days; the second group were only treated with acid solution for 21
      days; the third group were only attacked by MMP-1 solution for 7 days; and the
      fourth group were untreated as a control. Then all sections were dehydrated in
      ascending strength of alcohol, critically dried, coated with platinum, and then
      observed under scanning electron microscope(SEM). RESULTS: The dentin sections of
      root surface attacked by acid and MMP-1 showed that demineralization of dentin
      mineral and degradation of dentin matrix fibrae synchronously happened. The
      dentin matrix fibrae wasn't degradated in the groups treated with acid or MMP-1.
      CONCLUSION: The proteinases from human host may play an important role in the
      development of root surface caries. MMP-1 may distinctly degradate the organic
      matrix of demineralized dentin.

PMID- 15952620
TI  - [Study on lactate dehydrogenase activity of Streptococcus mutans isolates derived
      from caries-active and caries-free individuals].
AB  - OBJECTIVE: To preliminarily investigate the relationship between the Lactate
      dehydrogenase (LDH) activity of Streptococcus mutans (S. mutans) and dental
      caries initiation. METHODS: 100 S. mutans strains derived from caries-active and
      caries-free individuals were cultured in BHI medium supplemented with glucose.
      Cells were extracted and ruptured, and the extracted liquid protein was
      quantified with Coomassie brilliant blue G250 staining methods. LDH activity was
      assayed using the pyruvate-dependent oxidation of NADH-with and without FDP.
      RESULTS: LDH activity of the two groups strains had no difference (P > 0.05), but
      the distribution of differ class enzyme activity strains in the two groups was
      different (P < 0.05). CONCLUSION: LDH activity of S. mutans is correlated to the
      initiation of dental caries to some extent. The measurement methods in this study
      can be applied in preliminary quantitation of LDH activity and the screening of
      S. mutans strains.

PMID- 15952621
TI  - [Clinical analysis of 1 423 cases of root canal therapy].
AB  - OBJECTIVE: To evaluate the clinical quality of root canal therapy (RCT) in West
      China Dental Hospital of Sichuan University. METHODS: 1 423 RCT teeth were
      finished from Mar. 2001 to Feb. 2002 in West China Dental Hospital. Root canal
      filling quality and treatment period of these teeth were evaluated. 695 teeth of
      the total were revisited 2 years later and 2-year success rate were evaluated.
      RESULTS: The ratios of adequate filling, underfilling, and overfilling were
      79.97%, 14.62% and 5.41%, receptively. Full canal RCT ratio of molar was 89.44%.
      Average RCT treatment period was 2.8 weeks. 2-year success rate of RCT was
      94.39%. CONCLUSION: Clinical RCT level of West China Dental Hospital was
      satisfactory from 2001 to 2002.

PMID- 15952622
TI  - [Effect of Frankel function regulator on the condylar and mandibular positions of
      patients with class II malocclusion].
AB  - OBJECTIVE: To determine the positional changes of condyle and mandible in
      children treated successfully with Frankel function regulator. METHODS: 30
      Angle's class II patients including 15 boys and 15 girls treated with Frankel
      function regulator were selected. Superimposition of the pretreatment and
      posttreatment lateral cephalograms of all the patients was done on the stable
      bone structure of the anterior cranial base and mandible. Cartesian coordinate
      system was used to measure the positional changes of condyle and mandible over
      time by computer. RESULTS: There was significant inferior displacement of
      condyle, gonion and pogonion after treatment with reference to stable bone
      structure of anterior cranial base. Anterior displacement of pogonion in boys was
      also significant. There was significantly superior and posterior displacement of
      condyle and posterior displacement of gonion after treatment with reference to
      stable bone structure of mandible. CONCLUSION: Frankel function regulator can
      stimulate condylar growth and do favor to mandibular remolding.

PMID- 15952623
TI  - [A study on initial colonization of Mutans streptococci on teeth in infants and
      toddlers].
AB  - OBJECTIVE: To investigate the initial colonization of Mutans streptococci (MS) on
      teeth of children. METHODS: Dental plaque was collected from 123 children aged
      from 7 to 42 months. MS was isolated by culturing on selective medium and
      identified by biochemical tests. RESULTS: MS was detected in 51 of 123 children.
      The rate of colonization was 41.5%, and the mean age of colonization was 29
      month. The incidence of MS infection increased with age and tooth eruption, and
      reached peak at 25 - 31 months, which was statistically significant. There was a
      correlation between infection of MS and dental caries. CONCLUSION: The results
      indicate that the susceptive period of MS infection is from 25 to 31 months when
      the second primary molars erupt. MS infection is associated with dental caries.

PMID- 15952624
TI  - [The changes of bacteria group on oral mucosa after radiotherapy of postoperative
      patients of oral carcinoma].
AB  - OBJECTIVE: To investigate the microbial contents presented on the surface of
      mucosa in the oral cavity of patients who accepted radiotherapy, and to provide
      the evidences of controlling post-radiotherapeutic infections. METHODS: 32
      patients (19 males and 13 females) aged from 37 - 72 received radiotherapy after
      oral squamous cell carcinomas operation were selected. Samples of saliva were
      obtained from the radiated center and opposite mucosa before and after
      radiotherapy. The detective amount, detective ratio and constituent ratio were
      analysed by cultivation and identification. RESULTS: Streptococci, Candida
      albicans and Pseudomonas aeruginosa significantly increased on both sides of the
      oral mucosa while Neisseria and Actinobacillus decreased on radiated region after
      the radiotherapy. CONCLUSION: Radiotherapy has great effects on oral bacteria and
      pathogenic organism may play a role in post-radiotherapy infections. It is
      necessary to do bacteria culture and choose sensitive antibiotics regularly for
      post-radiotherapeutic patients.

PMID- 15952625
TI  - [The effects of desensitizing bonding system for prevention of vital abutment
      hypersensitivity].
AB  - OBJECTIVE: To evaluate the effects of GLUMA desensitizing bonding system in
      desensitizing hypersensitivity of vital abutment. METHODS: 69 central incisors
      with vital pulp from 69 patients were randomly divided into A, B and C group.
      After tooth preparation, group A coated with primer after etching, group B coated
      with primer after etching cervical dentin only, and group C was control group
      without special treatment. The cold sensitivity of abutments was tested after
      coating with primer, after cementation of crown and three months later. Two fresh
      extracted caries and restoration-free middle incisor were prepared in routine
      way. The surface of specimen 1 was etched with conditioner and the control
      specimen 2 was prepared without any special surface treatment. Scanning electron
      microscope (SEM) observation was used to examine the details on dentin surface.
      RESULTS: In all three times of examination, the sensitivities of two experimental
      groups had been significantly reduced compared with the control group.
      Immediately after coating, group B were more sensitive than group A (P < 0.05).
      After cementation of crown and three months later, there was no statistically
      significant between group A and group B. SEM photomicrograph showed that the
      smear layer was removed from etched dentine surface with open dentinal tubules.
      CONCLUSION: Coating with GLUMA desensitizing bonding system could prevent
      hypersensitivity of vital abutment.

PMID- 15952626
TI  - [Effects of varying the opaque thickness and the type of metal ceramic alloy on
      color].
AB  - OBJECTIVE: To compare the color differences of different metal bases and
      different opaque thickness, and evaluate the best thickness of opaque on
      different metal bases. METHODS: Precious metal, gold sediment and Ni-Cr plates
      were prepared as bases, then opaque samples of 0.05, 0.1, 0.2, 0.3, 0.4 and 0.5
      mm thickness were fabricated on such plates. Minolta chromatics meter CR-321 was
      used to examine the color properties of these samples, and deltaE was calculated
      to evaluate the color difference of the specimens. RESULTS: For the restoration
      based on Ni-Cr and precious alloys, the color of restorations was not affected by
      the color of metal bases as the thickness of opaque reached 0.3 mm, and the
      chromatic value deltaE < 1.5 NBS. For the restoration based on gold sediment, the
      color of restoration was not affected by the color of metal as the thickness of
      opaque reached 0.1 mm, and the chromatic value deltaE < 1.5 NBS. CONCLUSION:
      Different opaque thickness was necessary to obtain ideal color appearance in
      clinic. As the opaque thickness increased, the color of restoration based on Ni
      Cr and noble metal increased but the color of restoration based on gold sediment
      decreased.

PMID- 15952627
TI  - [2-year clinic effect of fluoride drop on dental caries prevention of primary
      teeth].
AB  - OBJECTIVE: To study the preventive effects of fluoride drop on dental caries for
      children. METHODS: The comparative method was carried out in 1 200 children aged
      from 3 to 4. The subjects were divided into three groups: fluoride drop group,
      fluoride toothpaste group and control group. The research period was 2 years.
      RESULTS: The results demonstrated that new dfs was 1.35 +/- 0.57 in the fluoride
      drop group after one year, 1.85 +/- 0.57 after two years. The new dfs was 1.53 +/
      1.09 in the fluoride toothpaste group after one year and 2.75 +/- 1.33 after two
      years. There was no significant difference of the dfs reduction between fluoride
      drop and toothpaste group. CONCLUSION: Fluoride drop is effective in the
      prevention of dental caries in Chinese kindergarten and primary school children.

PMID- 15952628
TI  - [Biological effects of nano-hydroxyapatite/polyamide 66 on the osteoblast].
AB  - OBJECTIVE: To evaluate the biological effects of nano-hydroxyapatite/polyamide
      66(nHA-PA66) on the growth and activity of osteoblast. METHODS: MTT assay was
      used to determine the growth of osteoblast, enzymatic measure was used to
      determine the activity of ALP and quantitative RT-PCR (QRT-PCR) to evaluate the
      changes of osteoclacin mRNA expression in osteoblasts treated by DMEM eluate of
      nHA-PA66. RESULTS: Osteoblasts of different test groups demonstrated relative
      proliferation rate ranging from 98% - 106% without dose-dependent effect. The ALP
      activity and osteocalcin mRNA expression were similar in test and control groups
      (P > 0.05). CONCLUSION: nHA-PA66 has no negative effects on the osteoblast and
      its osteoblast-compatibility is proved.

PMID- 15952629
TI  - [Osteogenic differentiation of synovial mesenchymal stem cells in vitro].
AB  - OBJECTIVE: To investigate the potential of synovial mesenchymal stem cells (SMSC)
      in osteogenic differentiation. METHODS: SMSC were obtained by limited dilution
      method and expanded to culture in 25-milliliter flasks. The attached cells were
      treated with inductive medium containing dexamethasone, glycerophosphate and
      vitamin C at 3rd passage SMSC. The mineralized nodule was stained by Von Kossa
      method. The expression of ALP and osteopontin were detected by histochemical,
      immunohistological staining technique, respectively, while the expression of
      cbfa1 mRNA by RT-PCR. RESULTS: Pure SMSC which were of spindle shape and star
      shape, uniform in size, could be induced to pleomorphism osteoblast in vitro,
      which were intensive positive in ALP and osteopontin. The expression of cbfa1
      mRNA were also verified by RT-PCR and the polygonal cells formed nodular
      structure at 4 weeks. All these were coincident with the characters of
      osteoblast. CONCLUSION: SMSC can be purified and induced into osteoblast in
      vitro.

PMID- 15952630
TI  - [Cultivation and induced differentiation of bone marrow stromal cells of SD rats
      with type I osteoporosis in vitro].
AB  - OBJECTIVE: To study the biological features and osteoblast/adipocyte phenotypes
      of bone marrow stromal cells (BMSCs) of Sprague-Dawley (SD) rats with Type I
      osteoporosis by induced culture. METHODS: Six-month-old SD rats were used in this
      study. 16 female rats were randomly divided into two groups. Eight rats were
      ovariectomied as experimental group to establish the modle of Type I
      osteoporosis, while other rats received sham-operation. Three month later BMSCs
      of 16 rats were isolated by discontinueous gradient centrifugation and then
      plated in alpha-MEM medium as primary culture. Secondary harvested cells were
      cultured for 14 days in alpha-MEM medium supplemented with dexamethasone,
      ascorbic acid, vitamin D3, beta-glycerophosphate or dexamethasone, 3-isobutyl-1
      methylxanthine, insuline, and indomethine. The cells were screened by inverted
      microscope each day and cell growth was studied with cell counting. The
      osteoblast and adipocyte phenotypes were verified by cytochemistry staining,
      counted the percentage of positive stained cells. RESULTS: The weight and bone
      mineral density of rats were statistically different between experimental group
      and control group. Gomori and Von Kossa's staining demonstrated positive
      osteoblast phenotypes of alkaline phosphatase and mineralized nods by osteogenic
      inducer, while Oil Red O staining identified BMSCs treated with adipogenic medium
      resulted in adipocyte formation and there was no significant difference in the
      percentage of positive stained cells between two groups. CONCLUSION: The model of
      Type I osteoporosis has been established successfully. BMSCs from SD rats with
      osteoporosis maintain their differentiation potential.

PMID- 15952631
TI  - [Study on multi-lineage potential of bone marrow mesenchymal stem cells derived
      from green fluorescent protein transgenic mice].
AB  - OBJECTIVE: To study the multi-lineage potential of bone marrow mesenchymal stem
      cells (MSCs) derived from transgenic mice with green fluorescent protein (GFP)
      gene in vitro. METHODS: A 6-week-old GFP transgenic mouse was executed by
      dislocation of cervical vertebra, and the marrow in tibia and thighbone was
      washed out with asepsis. The limited cell strains of MSCs derived from GFP
      transgenic mice (GFP-MSCs) were obtained with density gradient centrifugation.
      The passage 3 GFP-MSCs were induced to differentiate into osteoblast, adippcyte,
      neuron with solution of calcium induction medium, adipogenic medium and neural
      induction medium respectively. After being calcium-induced, the activity of
      alkaline phosphatase on GFP-MSCs was determined by micro-plate reader, and
      alizarin red staining was performed to test the formation of calcium
      concentration. The adipo-induced MSCs were detected with oil red O staining.
      Immunocytochemical staining was performed to detect the expression of NSE on
      neuron-induced MSCs. RESULTS: The ALP activity of GFP-MSCs heightened gradually
      along with being calcium-induced, and alizarin red staining showed positive. Oil
      red O staining of adipo-induced cells and NSE immunocytochemical staining of
      neuron-induced cells demonstrated positive. CONCLUSION: The limited cell strain
      of GFP-MSCs possesses multi-lineage potential, which can be used as an efficient
      tracking facility for studying the mechanism of multi-lineage potential on the
      MSCs.

PMID- 15952632
TI  - [The expression of TGF-beta1 mRNA in the maxillary sutures of puberty rhesus
      loaded with the class III intermaxillary orthopedic force].
AB  - OBJECTIVE: The purpose of the study is to detect the expression of TGF-beta1 mRNA
      in the maxillary sutures of puberty rhesus during different periods of the
      loading of intermaxillary class III orthopedic force. METHODS: The animal model
      was established with 6 puberty female rhesus, which were randomly divided into
      experimental group (wearing class III twin-block magnet appliance, each 2 rhesus
      for 3 and 6 month respectively) and control group (not wearing any appliance,
      each 1 rhesus for 3 and 6 month respectively). Tissue sections were obtained
      perpendicular to the sutures. In situ hybridization was used to the expression of
      TGF-beta1 mRNA, and the expression intensity was measured and statistics was
      performed by SPSS 11.0. RESULTS: There were no statistic differences of cellular
      density between palatomaxillary suture in vertical group and pterygomaxillary
      suture in horizontal group, but statistic differences were found between other
      groups. The expression of TGF-beta1 mRNA was detected in the control group, but
      the expression intensity was obviously increased after the load of intermaxillary
      class III orthopedic force. Statistically significant differences were found
      among all groups except the six months experimental group and control group of
      temporozygomatic sutures and pterygomaxillary sutures. Experimental groups were
      more intensive than the control group and three months group was more intensive
      than the six months group. CONCLUSION: The active tissue remodeling happened in
      the circummaxillary sutures by the effect of class III intermaxillary orthopedic
      force. Cell proliferation, extracellular matrix synthesis and bone formation were
      accelerated. During the different remodeling periods, the expression intensities
      were different, which may be related to the different force loading manners, the
      different reaction of sutures to the orthopedic force and the different
      biological function of TGF-beta1 in the different periods.

PMID- 15952633
TI  - [Analysis of chromosome karyotype of oral carcinoma-associated fibroblasts].
AB  - OBJECTIVE: The purpose of this study was to investigate whether the fundamental
      genetic character of oral carcinoma-associated fibroblasts changes through
      contrasting and analyzing the oral carcinoma-associated fibroblasts and the
      normal fibroblasts of oral mucosa. METHODS: The two kinds of cells were treated
      with colchicine and microsometic fluid, and then were expanded with cold acetic
      acid and formalized with methyl alcohol. The cells were observed under the oil
      microscope after Giemsa staining. The chromosome karyotype of the two kinds of
      cells was analyzed by Visus 2. 1. RESULTS: There were not obvious differences in
      the way of chromosome karyotype between the oral carcinoma-associated fibroblasts
      and the normal fibroblasts of oral mucosa. CONCLUSION: The basic genetic
      characteristics of the normal cells are conserved in the oral carcinoma
      associated fibroblasts, which means the cells have no malignant changes.

PMID- 15952634
TI  - [The integrin beta1 mRNA changes after orthodontic movement of teeth in
      periodontitis rats].
AB  - OBJECTIVE: To study the integrin beta1 mRNA changes after orthodontic tooth
      movement in normal teeth and periodontitis teeth of rats. METHODS: The OD of
      positively stained osteoclasts for integrin beta1 mRNA using in situ hybridzation
      was detected after orthodontic tooth movement in normal teeth and periodontitis
      teeth groups. RESULTS: Integrin beta1 mRNA expression were detected on all
      osteoclasts in tooth movement samples of normal and periodontitis teeth. There
      were stronger positive signals after given orthodontic force in both of the two
      groups. But no differences were found after 0.5, 1, 2, 3, 5, 7, 10 days since
      orthodontic tooth movement. The integrin beta1 mRNA signals in normal tooth
      movement group were not different from that in periodontitis group. CONCLUSION:
      The integrin beta1 of osteoclasts may play a role in the stability and remodeling
      of periodontal ligament in orthodontic tooth movement. There were no difference
      in the OD of integrin beta1 mRNA staining in orthodontic tooth movement between
      normal teeth group and periodontitis teeth group.

PMID- 15952635
TI  - [The relationship of abnormal expression of cell glucoprotein with recurrence of
      pleomorphic adenoma in salivary gland].
AB  - OBJECTIVE: To study the relationship of expression of mucin 1 and E-cadherin with
      recurrence of pleomorphic adenoma in salivary gland, and to investigate the
      signal to predict the recurrence potential of the tumor. METHODS: ; The capsule
      of tumor was observed by microscope. The expression of mucin 1 and E-cadherin in
      33 cases of primary adenoma, 12 cases of recurrent pleomorphic adenomas and 7
      cases of malignant pleomorphic adenomas were detected by immunohistochemistry.
      RESULTS: There was no significant difference about the status of capsule and the
      positive rate of mucin 1 expression between primary and recurrent pleomorphic
      adenoma (P > 0.05). The abnormal distribution of mucin 1 expression was observed
      in recurrent pleomorphic adenoma (6/8), which was characterized by the positive
      staining of the whole cytomembrane. On the other hand, positive staining of the
      primary pleomorphic adenoma was observed on the top of the membrane (19/21). The
      difference was statistically significant (P < 0.05). The staining pattern in
      malignant pleomorphic adenoma was similar with the recurrent ones except higher
      ratio of positive expression. No significant different was observed among the
      three kind of tumors on the expression rate of E-cadherin (P > 0.05). CONCLUSION:
      The status of capsule didn't have much actual usage in predicting the recurrence
      of pleomorphic adenoma. There was no significant relationship between the
      expression of E-cd and the recurrence of the tumor. The abnormal distribution of
      mucin 1 expression contributes to the invasiveness of the tumor and can be used
      as the predictive signal for recurrence of pleomorphic adenoma.

PMID- 15952636
TI  - [The study on three-dimension finite element analysis of the stress distribution
      in the mandible bone around dental implants].
AB  - OBJECTIVE: The aim of this study was to investigate how to model an accuracy 3
      dimension Finite Element Analysis (3D-FEA) model. METHODS: Based on computed
      tomography (CT) scan data of a woman, a 3D finite element model of the first
      molar on the left was rebuilt by computer imagines process and computer aided
      design (CAD). Analysis of the stress distribution on a cylinder dental implant
      and in the bone around it was conducted. RESULTS: The stress distribution showed
      extremely asymmetry in bucco-lingual section: stress concentrated on the lingual
      side of the mandible; stress mainly was tensile in buccal side, and on the
      contrary compressive in lingual side. CONCLUSION: The results were more reliable
      because this model more really displayed the mandible.

PMID- 15952637
TI  - [Expression and secretion of human tumor necrosis factor gene transfected on
      human embryo myoblasts].
AB  - OBJECTIVE: To observe human tumor necrosis factor-alpha (hTNF-alpha) expression
      and secreting level of human embryo myoblasts transfected by hTNF-alpha gene.
      METHODS: Human embryo myoblasts were transfected with shuttle plasmid pSV23SHTNF
      containing hTNF-alpha gene by cationic liposomes DOSPER. The control group was
      only given equivalent liposomes except plasmid. After culturing for 24, 48, 72
      and 96 hours, hTNF-alpha expression level of human embryo myoblasts was observed
      with immunocytochemistry staining, and hTNF-alpha secreting of human embryo
      myoblasts was analyzed by ELISA. RESULTS: After transfected by hTNF-alpha gene
      for 24, 48, 72 and 96 hours, the human embryo myoblasts displayed significant
      secretion of hTNF-alpha in the cultural supernatant (P < 0.05), and
      overexpression in cytoplasma and cell membrane. CONCLUSION: Transfection of hTNF
      alpha gene to human myoblasts made myoblasts secrete high concentration of hTNF
      alpha, implying it is feasible that transfecting muscle cells surrounding tongue
      carcinoma lesion with hTNF-alpha gene can prevent tongue carcinoma from intruding
      into deeper muscle tissue.

PMID- 15952638
TI  - [The malocclusion of primary dentition in the suburb of Chengdu: a cross-section
      survey].
AB  - OBJECTIVE: To reveal malocclusion of primary dentition in the suburb of Chengdu.
      METHODS: Cross-section survey and malocclusion rate calculation were performed.
      RESULTS: There are 491 children with malocclusion from total 1 279 children; the
      rate of malocclusion is 38.38%. The most important malocclusion in primary
      dentition are over bite (III degrees), anterior cross bite, edge to edge bite,
      early loss of deciduous teeth, fused teeth. CONCLUSION: The rate of malocclusion
      of primary dentition in the suburb of Chengdu is a little bit light. Much work
      should be done to prevent or treat the malocclusion of primary dentition.

PMID- 15952639
TI  - [Analysis of the literature in West China Journal of Stomatology cited by science
      periodical embodied by Chinese biological medical disc].
AB  - OBJECTIVE: The literature published in West China Journal of Stomatology (WCJS)
      cited by science periodical from 1983 to 2001 were analyzed to evaluate the
      academic level and quality of WCJS. METHODS: The cited literature was searched by
      Chinese biological medical disc (CBMDisc) from 1983 to 2001. The distributions of
      the times, the periodical and the authors were described. RESULTS: The quantities
      of cited literature were 1 338 and increased with years. The periodical and the
      authors were 266 and 1 003 respectively from 1998 to 2001. The cited frequencies
      of stomatological periodicals were more than that of other academic periodical.
      The authors scattered in 32 provinces and 448 units of China. The medical
      university and affiliated hospital were 32.14%, the local hospital and
      stomatological dispensary were 54.69%, the military hospital was 10.71%, and
      other unit was 2.46%. CONCLUSION: The literature published in WCJS are superior
      in quality. The cited frequency of WCJS is high relatively. WCJS is one of the
      most important informational source of stomatology.

PMID- 15952640
TI  - [Reform steps of reestablishing disease prevention and control system of China].
AB  - OBJECTIVE: To develop and demonstrate the reform steps of reestablishing disease
      prevention and control system of China. METHODS: A model named "strategies of
      fulfilling public functions of disease prevention and control system of China"
      has been employed to develop reform steps. 154 centers for disease prevention and
      control (CDC) have been sampled to consult the opinions about the reform steps
      developed by research team. RESULTS: To reestablish the disease prevention and
      control system of China, the following reform steps should be kept to: (1)
      increase government's attention to disease prevention and control, (2) insure
      feasible government investment to disease prevention and control, (3) increase
      the stability and efficiency of government financing, (4) reform management
      system to enhance the operation efficiency of the CDC, (5) revise labor
      regulation to attract and stabilize specialists, (6) be carefully to dispose the
      non-public-service now delivered by the CDC. The consent percent of all sampling
      CDC was 98.7%.

PMID- 15952641
TI  - [A study on the cause of public health service delivery insufficiency of disease
      prevention and control system of China].
AB  - OBJECTIVE: To demonstrate the cause of public health service delivery
      insufficiency of disease prevention and control system of China. METHODS: 205
      literatures in 8 national academic journals concerning health service management
      have been reviewed. The method of boundary analysis has been employed to conclude
      the various causes of public health service delivery insufficiency of disease
      prevention and control system of China. RESULTS: Literatures review demonstrated
      that the financing from government to disease prevention and control system of
      China was insufficiency and show lower efficiency, which has been agreed by 99.3%
      of CDC. Literatures review demonstrated that the financing administration idea of
      permitting charging service caused the fee-for-service played a key role in the
      economic reimbursement of various levels of CDC, which has been agreed by 96.0%
      of CDC. CONCLUSION: The causes of public health service delivery insufficiency of
      disease prevention and control system of China were the government financing
      insufficiency and the defective administration strategies.

PMID- 15952642
TI  - [Fundamental strategies to address the problem of public health service delivery
      insufficiency of disease prevention and control system of China].
AB  - OBJECTIVE: To develop and demonstrate the strategies to solve the problem of
      public health service delivery insufficiency of disease prevention and control
      system of China. METHODS: 205 literatures in 8 national academic journals
      concerning health service management have been reviewed. The method of boundary
      analysis has been employed to conclude the various reform strategies. Based on
      the causes and mechanism of public health service delivery insufficiency of
      disease prevention and control system, the logic analysis has been employed to
      develop fundamental strategies, which has been demonstrated by 154 CDC using
      intention questionnaires. RESULTS: There are fundamental strategies to which the
      agreeing rate for sampling CDC was over 95%: to make sure government should
      afford the financing function of disease prevention and control and secure the
      feasible investment for centers of disease prevention and control. Meanwhile, the
      working efficiency of CDC should be improved through strengthening management and
      reforming government investing manner.

PMID- 15952643
TI  - [Metallothionein isoforms gene expression induced by cadmium in human peripheral
      blood lymphocytes].
AB  - OBJECTIVE: To explore gene expression of metallothionein 1 (MT-1) isoforms in
      human peripheral blood lymphocytes. METHODS: mRNA of expression representing the
      seven active subtypes of MT-1 gene was determined in cultured human peripheral
      blood lymphocytes (HPBLs) before and after exposure to cadmium by quantitative RT
      PCR. RESULTS: Basal expression of MT-1X, MT-1A in HPBLs was similar to expression
      of the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase. In contrast,
      the basal gene expression of MT-1H, MT-1F, MT-1E, MT-1G was a little transcript
      in HPBLs. No signal was detected for the MT-1B. There was a sex difference (P <
      0.05) in basal gene expression of MT-1E. The level of gene expression of MT-1A,
      MT-1E, MT-1F, MT-1G, MT-1H and MT-1X was significantly increased (P < 0.05), but
      not the level of MT-1B after exposure to cadmium. CONCLUSION: It was suggested
      that gene expression of MT-1F, MT-1G, MT-1H and 1X in HPBLs could be used as
      potential exposure biomarker.

PMID- 15952644
TI  - [Study of IL-8 overexpression in A549 cells induced by crocidolite fibers].
AB  - OBJECTIVE: This study was to investigate the effect of crocidolite fibers on IL-8
      protein and mRNA levels in A549 cells cultured supernatant and the role of
      tyrosine kinase inhibitor PD98059 on IL-8 expression. METHODS: Real Time PCR and
      ELISA were employed to detect A549 cellular IL-8 mRNA and supernatant IL-8
      protein, respectively. RESULTS: After incubating cells with 100 microg/ml of
      crocidolite, IL-8 protein releasing in supernatant was significantly increased
      and IL-8 mRNA was also higher than that of control, the differences were
      statistically significant (P < 0.05), however both IL-8 protein and mRNA was
      abrogated by pretreating cells with tyrosine kinase inhibitor PD98059.
      CONCLUSION: IL-8 was shown as overexpression and could be decreased by PD98059.
      This indicated that MAPK signal pathway is involved in the process IL-8
      expression.

PMID- 15952645
TI  - [Identification of the related gene of mouse tolerant to exposure to
      perfluoroisobutylene by DDRT-PCR].
AB  - OBJECTIVE: The mice surviving acute exposure to low dose of perfluoroisobutylene
      (PFIB) could tolerant to lethal dose of PFIB. Discovering the gene related with
      the tolerance would be significant to find preventive agents for PFIB. METHODS:
      By static exposure to PFIB for 3 times, the survival animals could tolerate to
      lethal dose of PFIB. Three anchoring primers and 4 arbitrary primers were applied
      in differential display reverse transcription PCR (DDRT-PCR) of lung tissues and
      the products were analyzed by sequencing PAGE and silver staining. The
      differential DNA fragments were cloned and sequenced. RESULTS: There were obvious
      differences of gene expression between control and tolerant animals. Three
      expressed sequence tags (EST) have been cloned and sequenced,which were
      homologous to some mouse gene in Genbank. CONCLUSION: Specific gene up-regulation
      might be the cause of tolerance to PFIB, and they are very important to clarity
      the tolerant mechanisms to PFIB.

PMID- 15952646
TI  - [Study on the relationship between methylene tetrahydrofolate reductase gene
      (677C-->T) mutation and skin lesions in endemic arsenic poisoning].
AB  - OBJECTIVE: Methylene tetrahydrofolate reductase (MTHFR) is the key enzyme in
      folate metabolism. We examined whether single nucleotide 677 C-->T mutation in
      the MTHFR gene could affect the occurrence of skin lesions in endemic arsenic
      poisoning. METHODS: Fifty individuals with arsenic-induced skin lesions were
      identified as cases, and 35 individuals without skin lesions from the same
      village were selected as controls. The MTHFR C677T polymorphism was analyzed by
      PCR-RFLP method, serum folic acid and Vitamin B12 were determined by
      microbiological assay and the electrochemiluminescence immunoassay, respectively.
      RESULTS: The frequencies of TT genotype and T allele in case group were 34.0% and
      56.0%, respectively, and were not significantly different from those in controls.
      There was no significant difference between case and control group in the levels
      of folic acid and Vitamin B12 in serum. Compared to subjects carrying the CC
      genotype and having the level of folic acid above 10.5 nmol/L, other subjects
      were at elevated risk of skin lesions, but the 95% CI of both crude OR and
      adjusted OR (controlled for age, gender, smoking and arsenic level in drinking
      water) include 1. CONCLUSION: This study did not find the relationship between
      MTHFR gene (677C-->T) mutation and skin lesions in endemic arsenic poisoning.

PMID- 15952647
TI  - [Effective molecular form of alpha-tocopheryl succinate in inducing apoptosis of
      SGC-7901 cells].
AB  - OBJECTIVE: In order to explore the effective molecular form of alpha-tocopherol
      succinate (alpha-TOS) in inducing apoptosis of human gastric cancer SGC-7901
      cell. METHODS: Apoptosis was detected by DAPI staining and DNA ladder, prior to
      the treatment of cells with alpha-TOS (5 microg/ml, 10 microg/ml and 20
      microg/ml) for 48h, alpha-tocopherol (alpha-TOH) (20 microg/ml) and ethanol 1
      microl/ml as control groups. HPLC was also used to examine alpha-TOS and alpha
      TOH in the cells as well as culture medium. RESULTS: The observation of DAPI
      showed that the chromatin in karyon of SGC-7901 cells in the 10 microg/ml and 20
      microg/ml groups was concentrated with karyopyknosis and karyorrhexis, which were
      not found in other groups. Typical DNA ladders were obvious in the cells post
      administration of alpha-TOS at concentrations 10 microg/ml and 20 microg/ml. It
      was alpha-TOS not its hydrolyzed product alpha-TOH that was screened out by HPLC
      in cells and culture medium. CONCLUSION: alpha-TOS was capable of inducting the
      apoptosis of SGC-7901 cells in its intact form and was independent of alpha-TOH.

PMID- 15952648
TI  - [Survey on the contamination of microcystin-LR in water supply of Shanghai city].
AB  - OBJECTIVE: To study the pollution level of microcystin-LR in water supply of
      Shanghai city and the removal efficacy for microcystin-LR through routine water
      treatment technique. METHODS: High performance liquid chromatogram (HPLC) was
      applied to determine the concentration of microcystin-LR in source water, water
      samples after various water treatment procedures and tap water. RESULTS: The
      concentration of microcystin-LR varied with sampling seasons and sites and
      reached peak during summer and fall. The maximum of microcystin-LR was 2.38
      microg/L in source water. Coagulation plus chlorine disinfection were found to be
      effective for the removal of microcystin-LR, while the remove rate through
      filtration was not significant. And it could also be detected in tap water as
      high as 1.27 microg/L. CONCLUSION: The source waters of Shanghai city were
      polluted by cyanobacteria toxins represented by microcystin-LR. The source water
      in suburb was more polluted. Routine water treatment techniques can not remove
      the toxins effectively.

PMID- 15952649
TI  - [Effect of 900Mhz electromagnetic fields on energy metabolism in postnatal rat
      cerebral cortical neurons].
AB  - OBJECTIVE: To study the effect of 900MHz low intensity microwave electromagnetic
      fields (EMF) on AMPA GluR2 and the concentration of intracellular calcium in
      postnatal rat cerebral cortical neurons. METHODS: Neurons were exposed to low
      intensity 900MHz continuous microwaves EMF (SAR = 3.22W/kg, 2.23W/kg, 1.15W/kg)
      for 2 hours per day in 4 or 6 consecutive days and for 12 hours at a time (SAR =
      3.22W/kg). Such exposures were carried out to have knowledge of the effect of
      microwave on protein of GluR2 and intracellular calcium ions. RESULTS: The
      results of immunochemistry and laser confocal scan showed that compared with
      sham, protein of GluR2 of exposed neurons were significantly down-regulated (P <
      0.01), while intracellular calcium ions were significantly up-regulated (P <
      0.01). CONCLUSION: The microwaves play a role of accumulation in the effect on
      exposed neurons, the trends in dose response relationship were found between the
      exposure intensity and the effects, effect of the microwave on exposed neurons
      should be classified as athermal effects of EMF.

PMID- 15952650
TI  - [Effects of alcohol on the expression of heat shock protein 70 and super
      microstructure of astrocytes in rat embryonic brain].
AB  - OBJECTIVE: To explore effects of alcohol on the expression of heat shock protein
      70 (HSP70) and super microstructure of astrocytes. METHODS: Different dosage of
      alcohol (1, 5, 25, 50mmol/L) was administered to astrocytes of rat embryos.
      Effects of alcohol on expression of HSP70 were studied by immunocytochemistry,
      and changes of super microstructure of astrocytes were observed by electron
      microscope. RESULTS: The results showed that with increase of alcohol dosage, the
      expression of HSP70 increased, hepatin granule and survival astrocytes in
      25mmol/L and 50mmol/L dosage group decreased, cell membrane and mitochondrion
      were damaged, and even apoptosis and necrosis occurred. CONCLUSION: It suggested
      that alcohol could increase expression of HSP of astrocytes, which could depress
      the expression of normal function protein, and mainly impaired cell membrane and
      mitochondrion, which could lead to apoptosis and necrosis.

PMID- 15952651
TI  - [Study of period and area factors of manganese exposure on the postnatal
      development of brain in rats].
AB  - OBJECTIVE: To investigate the effects of period and area factors of manganese
      exposure on the postnatal development of brain in rats. METHODS: A combination of
      GFAP cytoimmunochemistry and imaging analysis was used to determine the
      morphological changes of glial cells and the average proportional densities of
      GFAP-immunochemistry positive products of different brain areas in different Mn
      exposured period. RESULTS: (1) In both one month's and two month's groups, no
      differences were found in the GFAP-immunochemistry extensities and the average
      proportional densities of GFAP reaction positive products between the Mn
      exposured group and the control group in the somatic motor and sensory cortexes,
      but in the expyramid nuclei or areas, that were increased significantly than the
      the control group. (2) In three month's Mn-exposured groups, the GFAP
      immunochemistry extensities and the average proportional densities of GFAP
      reaction positive products in all related areas of three groups were previously
      increased than that of the control group. CONCLUSION: In the interferential
      factors of manganese exposure on the postnatal brain development, both the Mn
      exposure period and the areas were the important ones.

PMID- 15952652
TI  - [Comparative study on the mutagenicity of the gasoline-fueled vehicle exhaust and
      methanol-fueled vehicle exhaust].
AB  - OBJECTIVE: In order to compare the mutagenicity of the gasoline-fueled vehicle
      exhaust (gasoline exhaust for short) and the methanol-fueled vehicle exhaust
      (methanol exhaust for short), provide a scientific basis for replacement gasoline
      by methanol as fuel in vehicle. METHODS: The Ames assay and A549 cell
      micronucleus test in vitro were applied to compare the mutagenicity of gasoline
      fueled vehicle exhaust and methanol-fueled vehicle exhaust. RESULTS: The results
      showed that the gasoline-fueled vehicle exhaust expressed evident mutagenicity in
      Ames assay (TA98 strain) with or without rat liver-derived metabolic activation
      system (S9). The mutagenicity increased obviously when S9 was used and showed a
      good dose-response relationship. However, the methanol-fueled vehicle exhaust did
      not show any mutagenic potential in Ames assay (TA98, TA100 strains) with or
      without rat liver-derived metabolic activation system (S9). In A549 cells
      micronucleus test in vitro, between 0.025 - 0.2JL/ml, the rate of A549 cells
      micronucleus could be induced by the gasoline-fueled vehicle exhaust. For the
      methanol-fueled vehicle exhaust, there was no significant differences in the rate
      of A549 cells micronucleus between the tested groups and control. CONCLUSION: The
      results strongly suggested that the gasoline-fueled vehicle exhaust had potential
      mutagenicity and the methanol-fueled vehicle exhaust did not show any potential
      mutagenicity. The results also provided a scientific basis for replacement
      gasoline by methanol as fuel in vehicle.

PMID- 15952653
TI  - [Study of toxicity on male reproductive system of mice induced by SO2
      inhalation].
AB  - OBJECTIVE: In this paper, toxicity of SO2 on male reproductive system of mice was
      studied. METHODS: 40 mice were divided to 4 groups (10/group): a group for
      control, the other 3 groups for SO2 inhalation (28, 56, 112mg/m3), 4h/d, 7d.
      RESULTS: The activities of GST and G-6-PD, as well as the content of GSH
      decreased significantly with SO2 increased. The content of MDA increased
      evidently with SO2 increased. CONCLUSION: SO2 can influence GSH oxidation
      deoxidation system and cause DNA damage in male reproductive system of mice.

PMID- 15952654
TI  - [Study on the oxidative injury of the vascular endothelial cell affected by
      PM2.5].
AB  - OBJECTIVE: To study the mechanism of cardiovascular disease affected by PM2.5.
      METHODS: ECV304 cells were exposed to PM2.5 of different concentration (50, 200
      and 400 microg/ml), after 24h, the viability of cells by MTT, SOD and GSH
      contents in cells and apoptosis of cells determined by flow cytometer were
      measured. RESULTS: Viability of ECV304 cells declined and mortality of ECV304
      cells increased gradually with increase of concentration, GSH contents in cells
      (mg/g prot) were 20.643 +/- 2.167, 16.774 +/- 2.911 (P < 0.05), 15.658 +/- 3.471
      (P < 0.01), and SOD contents in cells (U/mg prot) were 5.878 +/- 0.401, 5.140 +/-
      0.448 (P < 0.01), 4.817 +/- 0.451 (P < 0.01) when the concentration of PM2.5 was
      50, 200 and 400 microg/ml. CONCLUSION: PM2.5 can cause vascular endothelial cells
      to die by way of oxidative injury, then induce cardiovascular disease.

PMID- 15952655
TI  - [Application with single-stranded probes in randomized terminal linker-dependent
      PCR].
AB  - OBJECTIVE: Preparing single-stranded (ss) probes in place of double-stranded (ds)
      probes to improve the hybridization efficiency and specificity of randomized
      terminal linker-dependent PCR (RDPCR). METHODS: Using asymmetric PCR and single
      primer PCR to prepare ss probes of extron 7 of p53 gene in rat, then comparing
      the results hybridized with ss probes and ds probes. RESULTS: Preparation of ss
      probes by asymmetric PCR and single-primer PCR gets success. Hybridization
      results showed that the ss probes could get better signals and less noise than ds
      probes. CONCLUSION: In comparison with ds probes, the application of ss probes
      can increase the hybridization sensitivity and specificity of RDPCR.

PMID- 15952656
TI  - [Effects of ginsenoside Rb1 on mouse embryonic development in vitro].
AB  - OBJECTIVE: To evaluate the developmental toxicity of ginsenoside Rb1 and the
      potential mechanism of it in vitro. METHODS: Whole embryo culture system was used
      in this research. Embryos were exposed to various concentrations of ginsenoside
      Rb1, and scored for growth and development at the end of the 48h culture period.
      RESULTS: With the concentration of Rb1 rising, the total morphological scores
      significantly decreased; Developments of forebrain, midbrain and optic system
      were relatively sensitive to Rb1 and were affected at the concentration of 30
      microg/ml; hindbrain, Branchial arch and limb buds were affected at 50 microg/ml;
      Yolk sac was affected at the low concentration of 15 microg/ml and the indexes of
      embryonic growth and development decreased at the high concentration of 50
      microg/ml. Moreover, the rate of embryo teratogenicity were obviously increased.
      CONCLUSION: Ginsenoside Rb1 displayed teratogenic action in mice. The damage on
      structure and function of yolk sac might be part of teratogenic mechanisms of it.

PMID- 15952657
TI  - [Effect of zinc deficiency on femoral pathological and morphological changes in
      growth-term rats].
AB  - OBJECTIVE: This paper aims to clarify the effect of zinc deficiency on the bone's
      development in children by creating the growth-term rat model of zinc deficiency
      and to provide the theoretic basis for ways of bringing down the occurrence of
      hypeoevolutism to children. METHODS: Thirty weaning male rats were randomly
      divided into three groups: zinc adaquation (ZA), zinc deficiency (ZD), paired-fed
      (PF). After 15 days feeding, take the femurs to measure their length and
      diameter, to scale their weigh and to have their pathological tissue sections for
      observation of their pathological changes. RESULTS: The femurs of ZD group were
      significantly shorter than those of PF group and ZA group in length [(24.80 +/-
      0.42)mm & (26.70 +/- 0.48)mm & (27.90 +/- 0.32)mm, P < 0.01]. The femurs of ZD
      group were significantly smaller than those of PF group and ZA group in diameter
      [(2.09 +/- 0.09)mm & (2.70 +/- 0.08)mm & (2.80 +/- 0.08)mm, P < 0.01]. The femurs
      of ZD group were significantly lighter than those of PF group and ZA group in
      weight [(0.51 +/- 0.05)g & (0.65 +/- 0.08)g & (0.76 +/- 0.10)g, P < 0.01]. The
      histomorphology of left femur indicated that chondrocytes in the epiphyseal
      growth plate of ZD group were generally ill-organized and misshapen with the
      number of chondrocytes decreased. The trabecular bone in the epiphyseal of ZD
      group was also ill-organized, scarce and slim. The cavities of marrow in ZD
      animals were significantly larger than those of PF and ZA. The volume of
      trabecular bone, the mean trabecular plate density of ZD rats was significantly
      decreased, but their mean trabecular plate space was significantly increased.
      CONCLUSION: Zinc deficiency results in the morphological and pathological changes
      and affects the bone's growth and development.

PMID- 15952658
TI  - [Determination of rare earth elements in fetal kidney and cerebella by microwave
      dissolution and inductively coupled plasma-MS spectrometry].
AB  - OBJECTIVE: Study the contents of rare earth elements in normal fetal kidney and
      cerebella, and provide base data for the levels of rare earth elements in
      different phase of human development. METHODS: The samples were digested by
      closed-vessel microwave HNO3 + H2O2 dissolution system and directly tested by ICP
      MS for the contents of La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu
      in normal fetal kidney and cerebella. RESULTS: La mainly existed in fetal kidney
      (0.420 microg/kg), Ce mainly existed in fetal cerebella(0.363 microg/kg). Yb was
      little in both kidney and cerebella (0.103 microg/kg and 0.098 microg/kg). The
      contents of light rare earth elements in fetal kidney and cerebella were 1.427
      microg/kg and 1.236 microg/kg, the contents of medium rare earth elements in
      fetal kidney and cerebella were 0.469 microg/kg and 0.432 microg/kg, and the
      contents of heavy rare earth elements in fetal kidney and cerebella were 1.387
      microg/kg and 1.418 microg/kg. CONCLUSION: The rare earth elements all can be
      tested in fetal kidney and cerebella.

PMID- 15952659
TI  - [Regulation of chromium on gene expression of skeletal muscles in diabetic rats].
AB  - OBJECTIVE: To study the regulation of chromium on gene expression related to
      metabolism of skeletal muscles in diabetic rats. METHODS: Male Wistar rats were
      assigned to three groups: normal control group (NC), alloxan-induced diabetic
      control group (DM), and DM with chromium supplementation group (DM + Cr). 200
      microg Cr/kg bw perday was supplemented orally for 60 days. At the end of the
      treatment, the changes in gene expression among three groups were studied by mRNA
      differential display technique combined with cDNA fragments cloning, sequencing
      and BLASTn analysis. RESULTS: 11 cDNA fragments larger than 400bp expressed
      differences in skeletal muscles between DM + Cr group and DM group were isolated,
      4 of them expressed higher in DM + Cr group, while the rest expressed higher in
      DM group. Cr-3 and GLUT4 are homologous with sequence identities of 98% and Cr-5
      and IRS-1 are homologous with sequence identities of 100%. The expression level
      of GLUT4 mRNA in DM + Cr group are higher than those of DM group. CONCLUSION:
      Chromium supplementation could induce the expression of GLUT4 mRNA on skeletal
      muscles in diabetic rats. It may be one of the molecular mechanisms that chromium
      could improve the disorders of glucose and lipids metabolism in diabetic rats.

PMID- 15952660
TI  - [Determination of catechins and caffeine in tea and tea beverages by high
      performance liquid chromatography].
AB  - OBJECTIVE: A high-performance liquid chromatography method was developed for the
      determination of total tea catechin and caffeine. METHODS: The catechins needed
      to be determined are: (-)-catechin, (-)-epigallocatechin, (-)-epigallocatechin
      gallate, (-)-epicatechin, (-)-epicatechin gallate, (-)-gallocatechin, (-)
      gallocatechin gallate, (-)-catechin gallate and caffeine. The catechins in the
      tea was extracted with water:ethanol (3:7) by sonication for 20 min. After the
      extraction solution was centrifuged, it was analyzed by HPLC. The column used was
      a CAPCELL PAK C18 MG (4.6mm I.D. x 150mm) and gradient elution at constant column
      temperature with 30 degrees C under UV detector with 210nm. Mobile phase A was
      0.1% H3PO4 in water, mobile phase B was 0.1% H3PO4 in methanol with the flow rate
      1ml/min. RESULTS: The results showed that the concentration of the catechins and
      caffeine and their peak areas achieved good linear relation, r > 0.999. The
      recoveries were between 61.7%-117.3%. RSD was below 10%. With this method, some
      tea samples were determined, the results were favorable. CONCLUSION: The method
      can be applied for determination of catechin and caffeine in tea and tea
      beverages.

PMID- 15952661
TI  - [Effects of Icariin on ovariectomized osteoporotic rats].
AB  - OBJECTIVE: To observe the effects of Icariin on ovariectomized osteoporotic rats.
      METHODS: Female Wistar rats were ovariectomized and administered different dosage
      of Icariin and 17beta-estradiol for eight weeks. Bone mineral density (BMD),
      indexes of biomechanics and bone metabolism-associated biochemical markers were
      measured. RESULTS: Icariin increased the BMD, maximum load and flexural rigidity
      in the osteoporotic rats. The activities of serum tartrate-resistant acid
      phosphatase (TRACP) and bone alkaline phosphatase (BALP) were decreased in the
      Icraiin-fed ovariectomized rats. CONCLUSION: Icariin 225mg/kg per day could
      increase the BMD and improve indexes of bone biomechanics in ovariectomized
      osteoporotic rats. It was effective in preventing bone loss induced by
      ovariectomy.

PMID- 15952662
TI  - [Effect of antioxidant on hepatic stellate cell proliferation and apoptosis
      during recovery from liver fibrosis].
AB  - OBJECTIVE: Effects of dietary supplementation of vitamin E and selenium on
      proliferation and apoptosis of activated hepatic stellate cell(HSC) were
      investigated in the rat model of liver fibrosis induced by intraperitoneal
      injection with CCl4. METHODS: Activated HSC was determined by alpha-smooth muscle
      actin immunohistochemistry staining and apoptotic HSC determined by dual staining
      both of the terminal deoxynucleotidyl transferase UTP nick end labeling(TUNEL)
      and of alpha-smooth muscle actin immunohistochemistry. RESULT: During fibrosis
      recovery, the number of activated HSCs both in pathological group and in
      intervention group went down gradually,meanwhile, both the number of apoptotic
      HSCs and the collagen liver also descend little by little. These data confirmed
      that HSCs had the core effect on liver fibrogenesis and apoptosis may be a major
      factor regulating HSCs numbers during the injury-fibrosis-recovery sequence. At
      each time point, the number of activated HSCs in pathological group is more than
      intervention group, while apoptotic HSCs are less, which suggested dietary
      supplement with antioxidative nutrients had effect on HSC apoptosis but more
      studies are necessary to make the mechanism clearer. CONCLUSION: Dietary
      supplement with proper vitamin E and selenium can effectively lighten the hepatic
      fibrosis and promote the recovery of hepatocyte and the degradation of the
      existing collagens, ie, it is beneficial to the recovery of hepatic fibrosis.

PMID- 15952663
TI  - [Effect of malnutrition on the survival of children and productivity in 9
      provinces of China].
AB  - OBJECTIVE: To calculate the effects of malnutrition on the child survival and
      economic productivity in 9 provinces by using a new method. METHODS: PROFILES was
      used to quantify the function consequences of malnutrition in terms of child
      survival and productivity. RESULTS: As estimated, without improvement, 304000
      children will die due to underweight between 2001 and 2010 in 9 provinces,
      reducing underweight prevalence from 12.6% to 9.5% could save 38000 lives. If
      current stunting level remained unchanged over next 10 years in 9 provinces, the
      net present value of future productivity lost would be 58.4 billion, productivity
      gain due to reduction in child stunting reduced by 25% over next 10 years would
      gain worth 7.9 billion. CONCLUSION: Children's malnutrition plays a negative role
      in child survival, but also has huge economic lost in 9 provinces. It's
      recommendable to try or develop PROFILES model in nutrition study.

PMID- 15952664
TI  - [Effects of zinc on the expression of metallothionein isoforms in hippocampus of
      stressed rats].
AB  - OBJECTIVE: This study was conducted to evaluate the effects of different doses of
      zinc on the expression of metallothionein isoforms in hippocampus of stressed
      rats. METHODS: The animal model of psychological stress was developed by
      restraint stress for four weeks. Wistar rats were randomly assigned to eight
      groups as follows: control group, zinc deficiency group, pair-feed group, zinc
      complementarity group and their corresponding stressed groups. RESULTS: In zinc
      deficiency group, plasm zinc content was decreased, while in zinc complementarity
      group it's slightly increased. On the one hand, the expressions of
      metallothionein in brain and MT-1 mRNA, MT-3 mRNA in hippocampus were
      downregulated in zinc deficiency group, however, their expressions were evidently
      enhanced in stressed zinc deficiency group. On the other hand, inductions of
      metallothionein and it' s mRNAs in zinc complementarity group were increased,
      furthermore, stressed zinc complementarity group has more significantly yield of
      metallothionein and it' s mRNAs. In addition, the levels of plasma cortisol, IL
      6, IL-1 and NO were increased clearly in zinc deficiency group and stressed zinc
      deficiency group. CONCLUSION: Our results suggested that zinc deficiency may
      decrease while zinc complementarity increase the expressions of metallothionein
      in brain and MT-1 mRNA, MT-3 mRNA in hippocampus, moreover, stress can increased
      their expressions dramatically. The impairment of stress on body may be involved
      with the nutrition status of zinc, and zinc deficiency can lower the body's
      resistibility to stress.

PMID- 15952665
TI  - [Study on serum leptin level of urban resident and the relationship between body
      mass index, blood lipid, insulin and leptin level].
AB  - OBJECTIVE: To measure serum leptin concentration of urban residents and
      investigate the relationship between serum leptin concentration and body mass
      index(BMI), blood lipid, insulin. METHODS: One hundred fifty-eight men and women
      ages 18-72 years were initially drawn from a community in Ji'nan City. The
      parameters measured included height, weight, waist and hip circumference,
      insulin, blood lipid and leptin concentrations. Statistical analyses were
      performed with SPSS11.5. RESULTS: The mean serum concentration of leptin was
      (17.47 +/- 13.52)ng/ml, in male subjects was (8.38 +/- 6.31)ng/ml, in female
      subjects it was (24.98 +/- 13.29)ng/ml. Serum level of leptin was significantly
      positively correlated with BMI, waist and hip circumference, not correlated with
      WHR. Serum leptin level in females was positively correlated with WHR. There was
      no association between serum level of leptin and insulin. Serum leptin level in
      males was positively correlated to apo B, in females was positively correlated to
      TC, LDL-c. CONCLUSION: BMI is an important factor to determine serum leptin
      level. The relationships between plasma glucose, insulin, blood lipids and serum
      leptin are affected by gender. In males serum leptin level was positively
      correlated to apo B, in females was positively correlated to TC, LDL-c. We need
      further research to explain this difference.

PMID- 15952666
TI  - [Approaching Chinese diet balance index].
AB  - OBJECTIVE: To establish Chinese Diet Balance Index (DBI).; To evaluate the
      overall diet quality; To provide an effective measurement instrument for
      researchers, food and nutrition policy makers and the public. METHODS: The
      Dietary Guidelines for Chinese Residents motivated the selection of food-based
      components. The components were weighted and assigned cut-offs and point schemes
      based on the Chinese Food Guide Pagoda. Five scoring method are used to combine
      the component scores. RESULTS: 8 food-based components were selected, these are
      the intake of cereals, vegetable and fruit, bean and dairy, animal food, alcohol,
      salt, oil as well as the food variety. The scoring system including total score,
      lower bound score, higher bound scores, and diet quality distance can reflect
      both under and over intake. DBI can be used as a measurement to evaluate the
      dietary quality of the individual or the population.

PMID- 15952667
TI  - [Assessment of the BALB/c mice as a suitable animal model for the investigation
      of food allergy].
AB  - OBJECTIVE: This study was to develop a suitable model for the investigation for
      food allergy. METHODS: BALB/c mice were dosed by intraperitoneally with
      Ovalbumin, Beef serum albumin, Trypsin inhibitor and Potato acid phosphatase
      respectively (0.25ml 20mg/mnl) on day 0 and again on day 7. Control group was
      dosed with PBS. Sera form individual animals were analysed for specific IgE and
      Passive cutaneous anaphylaxis tests. Additionally, the level of histamine in
      plasma were detected. RESULTS: The high titres of specific IgE (1: 32) could be
      provoked in test groups compared with control group. In addition, the level of
      histamine in plasma of test groups was higher than that in the control group. But
      there was no statistical significance between group food allergen and group
      Potato acid phosphatase. CONCLUSION: Although allergic action of BALB/c mice
      could be provoked, the situation of the allergic action of BALB/c mice to the
      proteins was very different with the human being. The BALB/c mice could not be a
      suitable model for the investigation for food allergy.

PMID- 15952668
TI  - [Study of the genetic stability of expression plasmid vector pMG36e in host
      bacteria].
AB  - OBJECTIVE: To study the genetic stability of expression plasmid vector pMG36e in
      Escherichia coli JM109 and Lactococcus lactis MG1363/36e and observe the effect
      of erythomycin for its stability. METHODS: We used classical method to determine
      the genetic stable rates of pMG36e in E. coli JM109 and Lactococcus lactis
      MG1363/36e with or without erythomycin selective pressure. RESULTS: When E. coli
      JM109 were continuously incubated to 120 generations, its pMG36e genetic stable
      rates were 100% and 96% respectively with or without erythomycin selective
      pressure. When Lactococcus lactis MG1363/36e were continuously incubated to 100
      generations, its pMG36e genetic stable rates were the same 98%, with or without
      erythomycin selective pressure. CONCLUSION: pMG36e had good genetic stability in
      this two hosts. Erythromycin selective pressure had no significant effect for the
      genetic stability of pMG36e.

PMID- 15952669
TI  - [Study on the dietary protein bioavailability by young men of Yi and Tibetan].
AB  - OBJECTIVE: To compare the dietary protein intakes and bioavailability of young
      male adults of Yi and Tibetan. METHODS: Two groups of subjects aged from 18 to
      22y were respectively recruited from schools of Liangshan Yi autonomous region
      and Tibetan-Qiang autonomous region. Samples of diet, fecal and urine in the
      nitrogen balance study for each group of subjects were collected, and the
      nitrogen content was analyzed by semi-micro-Kjeldahl. RESULTS: Total protein
      intake, apparent absorption, true absorption, biological value, net protein
      utilization and nitrogen balance for the young man of Yi people were 71.55g/d,
      73.19%, 79.79%, 47.58%, 38.17% and 0.71g/d. The corresponding figures for young
      Tibetan man were 94.33g/d, 86.69%, 91.43%, 48.07%, 44.00% and 3.16g/d.
      CONCLUSION: The dietary protein intake and bioavailability of young Tibetan man
      were better than those of Yi, but both Yi and Tibetan young men were able to keep
      positive N balance with their respective dietary pattern.

PMID- 15952670
TI  - [Advances on study of organophosphate poisoning prevented by Huperzine A].
AB  - Currently, it is a concerned project in medicine to study the effective methods
      for treatment of organophosphate (OP) poisoning. Huperzine A is a potent,
      reversible red cells acetylcholinesterases (AChE) inhibitor, which shows high
      specificity for AChE preserving scavenger capacity of plasma
      butyrylcholinesterase (BuChE) for OP agents, and cross the blood-brain barrier
      smoothly preventing the AChE in CNS, so the CNS damages induced by the acute OP
      poisoning were prevented. These review summarizes the results of experimental in
      animals, prevention mechanism, and prevention value of HupA against OP poison.

PMID- 15952671
TI  - [Progress of molecular imprinting technique on the determination of pesticides
      residues].
AB  - People have paid a more attention to the pesticides residues, so the rapid
      detection method is required. In this paper the application of molecular
      imprinting technique on the detection of pesticides residues was reviewed,
      including recognition principles, preparation, current applications, problems and
      its future.

PMID- 15952672
TI  - [Relationship between maternal DHA intake and DHA status and development of fetus
      and infant].
AB  - The important physiological function of docosahexaenoic acid (DHA) is being the
      focus of nutriology fields. The DHA status of pregnant and lactation women, who
      are the main nutrition provider for fetus and infants, had an important effect on
      DHA nutrition and development of their fetus and infants. The infants whose
      mother had a supplement of DHA during pregnancy and lactation have higher blood
      DHA level and better development results of body, visual acuity and intelligence.
      This paper reviewed the recent international research data on the relationship
      between maternal DHA intake and DHA status and development of fetus and infant.

PMID- 15952673
TI  - [Studies on the antioxidant properties of tea].
AB  - It is reported that the water extract of tea as well as tea polyphenols and tea
      pigments have strong antioxidant properties, which are considered as the major
      mechanism of the protective effects of tea on cancer and cardiovascular diseases.
      It has been shown that tea (including tea polyphenols and tea pigments) could
      induce the antioxidant enzyme activities, regulate phase I and II metabolic
      enzymes, inhibit the metabolic activation of carcinogens, reduce the formation of
      carcinogen DNA adducts, inhibit the expression and replication of oncogenes,
      directly affect the activity of transcription factors, and block the initiation
      of carcinogenesis, so as to eliminate and alleviate the damage to cellular
      communication caused by oxidative stress, and eventually prevent the abnormal
      proliferation of tumor cells. The mechanisms of the protective effects of tea on
      cardiovascular diseases are possibly related to its effects on the inhibition of
      lipid oxidation and quenching oxygen and hydroxy free radicals. It was
      demonstrated that tea pigments could inhibit the oxidation of LDL cholesterol and
      the adhesion of blood vessel endothelium cells, lower endothelin levels, enhance
      GSH-PX activities, prevent from blood coagulation and platelet aggregation, and
      facilitate fibrinogen dissolution, so as to prevent atherosclerosis of coronary
      arteries.

PMID- 15952674
TI  - [Development of proteome two-dimensional electrophoresis technology].
AB  - Two-dimensional electrophoresis (2-DE) is the core technology of proteome study.
      This paper mainly introduces the 2-DE principle, sample preparation and usual
      methods to improve its resolving power. Furthermore, isoelectric focusing, SDS
      PAGE electrophoresis and 2-DE staining methods are also reviewed.

PMID- 15952675
TI  - [Strategies for safety assessment of genetically modified crops: current and
      future development].
AB  - Gene recombinant technologies supply agriculture product with great vitality. But
      the risk of genetically modified crops cannot be ignored. The international
      organizations such as WHO, FAO and OECD have reached common agreement: the safety
      of transgenic crops should be thoroughly evaluated based on "substantial
      equivalence"principle. The relevant strategies including: substantial equivalent
      analysis, toxic tests, protein allergenic study, nutritional assessment, etc.
      With the development of new technologies, the approaches of genomic, proteomics,
      metabolomics would be applied to detect the unintended effects. The EU recently
      adopted legislation on the cultivation GM crops requiring the post market
      surveillance for any unanticipated adverse effects in the long term. In
      conclusion, the strategies of the safety assessment of GM crop are very strict
      and likely development.

PMID- 15952676
TI  - [Molecular genetics on fumonisin-producing strains of Fusarium verticillioides].
AB  - Fumonisins are a group of mycotoxins produced by Fusarium verticillioides
      (synonym Fusarium moniliforme Sheldon). Fumonisin B1 has acute toxicity and
      potential carcinogenicity to some animals, causing leukoencephalomalacia in
      horses, porcine pulmonary edema (PPE) and liver cancer in rats. It was considered
      to be epidemiologically associated with high incidence of Human Esophageal Cancer
      (EC) in human. At present, the study on fumonisins has reached molecular levels.
      4 clustered and coregulated genes fum1, fum2, fum3 and fum4 associated with
      Fumonisin biosynthesis were identified through genetics study on Fumonisin
      producing strains of Fusarium verticillioides. The result of PCR with degenerate
      primers based on polyketide synthase (PKS) gene proved that fum5 was PKS gene
      required for fumonisin biosynthesis. Study on molecular biology of Fumonisin
      producing strains was also performed. Furthermore, transgenic strategies were
      used for ear mold resistance to Fusarium and reducing Fumonisin contamination in
      plants, to decrease the hazard to the health of both human and animals, as well
      as food safety.

PMID- 15952677
TI  - [Research progress in analysis methods of Aflatoxins].
AB  - Aflatoxins, a group of toxins structurally related to secondary metabolites are
      produced by some fungal strains. Many countries developed legislations to
      regulate and control aflatoxins in food and feed because they are extremely
      toxic, potent carcinogenic and ubiquitous in the environment. Different
      analytical methods are currently used: TLC, HPLC, ELISA, RIA, CE, and IC, etc.
      Developed quickly, nonpolluting and nontoxic analysis system will become the hot
      sport in the future.

PMID- 15952678
TI  - [Determination of pralidoxime chloride in rat plasma by high performance liquid
      chromatography].
AB  - OBJECTIVE: To provide a reference for clinically curing organophosphrous
      compounds Poisoning. A high performance liquid chromatography method has been
      developed for determination of pralidoxime chloride in rat plasma. BECKMAN ODS
      C18 column, Waters Model 510 HPLC pump and 996 photodiode Detector were used. The
      mobile phase consisted of 7.5% acetonitrile and 92.5% (20nmol/L NaH2PO4, 0.2%
      C8H17SO3 Na, pH3.0, adjusted by H3PO4 Solution) the flow rate was 1.0mol/min.
      detection wavelength was set at 296. The samples were pretreated with
      acetonitrite. The results show a good liner correlation between pralidoxime
      chloride concentration(from 1.0 - 5.0 microg/ml) and absorption intensity. The
      detection limit is 0.5 microg/ml with signal to noise ratio of 2. The intra-assay
      and inter-assay coefficients of variation were 1.35% and 2.73%. The recoveries
      for plasma were in ranges of 76% - 84%.

PMID- 15952679
TI  - Use of Remifentanil for sedo-analgesia in stapedotomy: personal experience.
AB  - Stapedotomy for otosclerosis presents particular anaesthesiology demands as the
      surgeon has to assess functional results during the operation, work with some
      bleeding, be ensured the collaboration of the patient, and limit the occurrence
      of intra- and post-operative symptoms (dizziness, nausea, vomiting and pain).
      Remifentanyl, a micro-opioid selective agonist characterised by short latency and
      duration, has been used for about 2 years at the Otolaryngological Unit of the
      "Federico II" University of Naples for patients with otosclerosis undergoing
      stapedotomy. Aim of the study was, therefore, to assess: efficacy and
      tolerability of Remifentanyl in combination with a local anaesthetic in surgical
      procedures for otosclerosis; intra- and post-operative reduction in patient
      symptoms of dizziness, nausea, vomiting and pain; reduction of intra-operative
      bleeding; degree of patient collaboration and optimisation of anaesthesiological
      and vital parameters monitored during surgery. The study was carried out on 92
      patients with otosclerosis, (17 M, 75 F), median age 41 years (range 25-56),
      undergoing stapedotomy. Patients were randomly assigned to one of two groups,
      which were homogeneous as far as concerns age, sex and pre-operative hearing: i.
      Group A (50 patients), received Remifentanyl infusion in combination with canal
      injection for local anaesthesia with Mepivacaine 2% and Adrenalin 1/100,000; ii.
      Group B (42 patients), received only local anaesthetic by infiltration of the
      external canal ear. Remifentanyl led to an improvement over the local anaesthetic
      technique previously used, with a clear decrease in intra- and post-operative
      neurovegetative symptoms such as dizziness, nausea, vomiting and pain, as well as
      reduced bleeding.

PMID- 15952680
TI  - SPET assessment of auditory cortex stimulation and tonotopic spatial distribution
      in auditory brainstem implant.
AB  - Activation of the auditory cortex by multifrequency acoustic stimuli has been
      evaluated using Single Photon Emission Tomography in a case of auditory brainstem
      implant after activation of 6 and 11 electrodes. Before implantation, no
      activation of the auditory cortex has been observed after acoustic stimulation.
      Following auditory brainstem implant, the stimulation of 11 electrodes showed an
      activation value, in terms of blood flow increase, of the contralateral temporal
      cortex similar to that obtained with 6 electrodes (47.70 vs. 43.76%), but a
      significantly stronger activation was present in the contralateral parietal
      region (29.59 vs. 14.73%), in the homolateral temporal area (22.02 vs. 10.46%)
      and, especially, in the homolateral parietal zone (16.6 vs. 4.33%). The strongest
      activation in the contralateral temporal cortex was detected in the sagittal
      tomogram at 26.25 mm from the midline, that is in the areas where high
      frequencies are projected, both with 6 and 11 active electrodes. The medio
      lateral auditory cortex, where the middle and lower frequencies are projected,
      showed an overall lower activation which was however significantly lower with 6
      electrode stimulation. Stimulation of the surface of cochlear nuclei determines
      mainly an activation of the high frequency domain, independently of the
      electrodes number. This finding may explain the better results of cochlear
      implants in comparison with auditory brainstem implant and could justify the use
      of needle electrodes in auditory brainstem implant. In conclusion, Single Photon
      Emission Tomography can be considered useful in evaluating auditory brainstem
      implant placement and function. It is also able to define the effectiveness of
      acoustic stimulation, the degree and tonotopic spatial distribution of auditory
      cortex activation.

PMID- 15952681
TI  - State and trait anxiety in patients affected by nasal polyposis before and after
      medical treatment.
AB  - The present study aimed to establish whether anxiety and depression in nasal
      polyposis play a role in genesis of the disease, or are a consequence of
      symptoms. Anxiety levels were evaluated in state and trait forms, and depression,
      in 30 consecutive patients presenting nasal polyposis before and after effective
      7 months' medical treatment with nasal mometasone, loratadine and montelukast.
      Before and at the end of treatment, patients were asked to fill in the State and
      Trait Anxiety Inventory and the Zung self-rating depression scale. In 63.15% of
      patients with high levels of state anxiety before therapy, these were reduced (p
      < 0.004) after treatment. In 61.9% of patients with high levels of trait anxiety
      before treatment, these were reduced (p < 0.002) after treatment. There were no
      significant differences in depression. Anxiety in nasal polyposis is present both
      as a state and as a trait, and is significantly reduced after effective medical
      treatment, showing that anxiety is a reversible consequence of nasal polyposis in
      most cases.

PMID- 15952682
TI  - Hereditary haemorrhagic telangiectasia: state of the art.
AB  - Hereditary haemorrhagic teleangiectasia (HHT) or Rendu-Osler-Weber disease is a
      genetic autosomal-dominant disorder characterised by the presence of vascular
      telangiectases in mucocutaneous tissues, visceral organs and the Central Nervous
      System. Pulmonary arteriovenous malformations have a variable incidence rate
      ranging between 15-33%, and the safest treatment is transcatheter embolotherapy.
      Haemmorrhages from the gastrointestinal tract occur in 10-40% of patients with
      HHT localized in duodenum and colon and can be treated with endoscopy and laser
      coagulation, but this procedure is not efficacious for vascular anomalies in
      small intestine since this site cannot be easily reached. The prevalence of
      cerebrovascular malformations in hereditary haemorrhagic telangiectasia patients
      is 5-27%, and there are several types described including telangiectasias,
      cavernous angiomas, arteriovenous malformations, and aneurysms. Cerebrovascular
      malformations can be treated by: neurovascular surgery, embolization, and
      stereotactic radiosurgery, but the appropriate course of action for dealing with
      asymptomatic cerebrovascular malformations is still debated. The most common
      symptom in HHT patients is epistaxis, which can sometimes be so profuse that it
      requires multiple transfusions and iron supplementation. Nose bleeds begin before
      10 years of age and become more severe in later decades. A multitude of different
      treatments are available, tailored to the severity of epistaxis. These include:
      hormonal therapy with oestrogens, application of fibrine tissue sealant, laser
      coagulation, embolization and septal dermoplasty using Saunder's technique. Aim
      of this study is to review diagnostic and therapeutic techniques, since
      continuous growth and danger of these arteriovenous malformations require early
      diagnosis, adequate treatment, prolonged follow-up and screening of the family.

PMID- 15952683
TI  - Multidimensional Voice Program (MDVP) and amplitude variation parameters in
      euphonic adult subjects. Normative study.
AB  - The introduction, in the late 70s, of the first digital spectrograph (DSP
      Sonograph) by Kay Elemetrics has improved the possibilities of spectroacoustic
      voice analysis in the clinical field. Thanks to the marketing, in 1993, of the
      Multi Dimensional Voice Program (MDVP) advanced system, it is now possible to
      analyse 33 quantitative voice parameters which, in turn, allow evaluation of
      fundamental frequency, amplitude and spectral energy balance and the presence of
      any sonority gap and diplophony. Despite its potentials, the above-mentioned
      system is not widely used yet, partly on account of the lack of a standard
      procedure. Indeed, there are still only a few case reports in the literature
      taking into consideration prescriptive aspects related both to procedure and
      analysis. This study aims to provide the results of amplitude perturbation
      parameter analysis in euphonic adult patients. In our opinion, these are the most
      significant parameters in determining the severity of a phonation disorder. The
      study has been carried out on 35 patients (24 female, 11 male, mean age 31.6
      years, range 19-59). The voice signal has been recorded using a 4300 B Kay
      Computer Speech Lab (CSL) supported by a personal computer including a SM48 Shure
      Prolog microphone located at a distance of 15 cm and angled at 45 degrees. Input
      microphone saturation has been adjusted to 6/9 of the CH1 channel. The voice
      sample consisted in a held /a/ and the analysis has been carried out on the
      central 3 seconds of the recording. The analysis has been carried out using a
      5105 MDVP software version 2.3 and the signal digitalised at a 50 kHz sample
      rate. In order for the sample to be as free from intensity or frequency changes
      as possible, each patient underwent a training session (including at least 3
      phonation tests) before the recording. The study included only emissions between
      55 and 65 dB and with spectrum stability. Environmental noise has constantly been
      monitored and maintained below 30 dB. Data from the 24 female patients showed:
      absolute Shimmer (ShdB) = 0.203 dB, relative shimmer (Shim %) = 2.226, amplitude
      perturbation quotient (APQ) = 1.758, smoothed amplitude perturbation quotient =
      3.309, peak amplitude variation (vAm) = 7.042. Data from the 11 males showed:
      absolute Shimmer (ShdB) = 0.269 dB, relative shimmer (Shim %) = 2.892, amplitude
      perturbation quotient (APQ) = 2.611, smoothed amplitude perturbation quotient
      (SAPQ) = 3.433, peak amplitude variation (vAm) = 6.385. Statistical analysis (t
      test) showed no statistically significant difference between sexes, thus a single
      set of rules was used for both sexes.

PMID- 15952684
TI  - The role of positron emission tomography (PET) in the management of cervical
      lymph nodes metastases from an unknown primary tumour.
AB  - Cervical lymph node metastases may be the initial manifestation of occult cancer.
      Despite a very exhaustive search, the primary site of approximately 2-10% of
      these tumours remain undetected. Evaluation of the patient includes: detailed
      physical examination of skin, upper airways (fiberoptic endoscopy), salivary
      glands and thyroid; fine-needle biopsy, multiple endoscopic biopsies, and imaging
      studies (ultrasonography, computed tomography scan or magnetic resonance
      imaging). Recently, positron emission tomography scan has been demonstrated to be
      a useful diagnostic imaging study in these patients. The records of 11 patients
      were reviewed. End-points were the usefulness of positron emission tomography in
      the detection of an unknown primary tumour and/or distant metastatic disease. In
      5 patients, positron emission tomography detected a primary lesion, confirmed
      pathologically and revealed distant metastases in 2 patients. Two cases were
      false-positive and 1 false-negative. In 3 patients no primary tumour was found
      after 3 years follow-up. In conclusion, positron emission tomography was not of
      any significant advantage in detecting occult primary tumour vs. computed
      tomography scan or magnetic resonance imaging. Positron emission tomography, as
      "ab initio" total body examination, is important in detection of unsuspected
      distant diseases.

PMID- 15952685
TI  - Surgery of thyroid cancer: twelve years' personal experience.
AB  - Diagnosis and treatment of thyroid carcinoma require a multidisciplinary
      approach. The close and long-standing collaboration between the
      Otorhinolaryngology, Pathological Anatomy and Nuclear Medicine Departments of
      Legnano Hospital has led to a precise diagnostic and therapeutic protocol in
      thyroid patients. In the 1990-2002 period, 131 patients underwent total
      thyroidectomy after diagnosis of thyroid cancer at the Otorhinolaryngology--Head
      and Neck Surgery Department. Patients submitted to lobectomy for differentiated
      thyroid cancer were excluded from the present study. The patient population is
      composed of 96 females (73%) and 36 males (27%) aged between 22 and 85 years. Of
      the 131 patients, 115 (87%) presented papillary carcinoma, 13 (10%) follicular
      carcinoma, 2 (2%) medullary carcinoma and one (1%) undifferentiated carcinoma.
      Two patients (2%) suffered from a preoperative monolateral recurrent nerve palsy.
      Total thyroidectomy was performed in all 131 patients. Selective neck dissection
      was performed only in patients with positive lymph nodes for papillary (37/115,
      32%) and follicular carcinoma histotype (2/13, 15%) and, in both patients with
      medullary carcinoma (100%). Of the 131 patients, 15 (11%) did not undergo routine
      follow-up and were, therefore, excluded from the study, the remainder completed a
      mean follow-up of 47 months. During follow-up, the incidence of the two most
      frequent complications of thyroid surgery were evaluated: recurrent nerve
      paralysis and permanent hypoparathyroidism (exceeding the postoperative 6
      months). Results of treatment have been evaluated considering the incidence of
      local and/or distant recurrences and patient survival rate. As far as concerns
      papillary and follicular histotype, we have considered as healed (absence of
      signs suggesting loco regional and distant recurrence) only those patients
      presenting both negligible levels of plasma thyroglobulin and a negative total
      body 131I scintigraphy. Briefly, in 3 cases (3%), all papillary carcinomas, local
      recurrence occurred; 9 (8%), all with papillary carcinoma, developed lateral neck
      recurrence; 6 (5%), 5 with papillary carcinoma and one with follicular carcinoma,
      developed distant metastases, of which 3 pulmonary, 2 bone and 1 hepatic. Serum
      thyroglobulin values were considered during the last control visit in 95/113
      patients (84%). Of these, 86 (91%) with negligible thyroglobulin levels and
      negative 131I scintigraphy, were considered healed. All 113 patients with
      differentiated thyroid carcinoma were alive at the last control visit. Both
      patients with medullary carcinoma are alive with no sign of illness at the last
      follow-up control. The patient presenting undifferentiated carcinoma died 2
      months after surgery. In conclusion, at the last follow-up control, 1 (1%)
      patient has died, 5 patients (4%) are alive with disease (2 of whom suffered from
      multiple recurrences) and the remaining 110 (95%) patients are alive without
      evidence of disease. As far as concerns complications of surgery, iatrogenic
      recurrent palsy and permanent hypoparathyroidism are present in 2 (2%) and 10
      patients (8%), respectively.

PMID- 15952686
TI  - A case of highly aggressive adenoid cystic carcinoma of the external auditory
      canal.
AB  - Tumours of the external auditory canal are extremely rare and only 20% of these
      are of glandular origin. The most frequent histotype is adenoid cystic carcinoma.
      The rarity of external auditory canal glandular tumours explains the lack of
      large series reported in the literature and the corresponding large number of
      case reports from different Authors. Adenoid cystic carcinoma, presenting in the
      external auditory canal, exhibits the same characteristics as those affecting the
      major salivary glands, this tumour has an aggressive behaviour characterized by
      local invasivity and with a metastatic risk of approximately 30%. A rare case of
      adenoid cystic carcinoma of the external ear is reported. The patient, a 75-year
      old male, had right intermittent otorrhea for 6 years. On examination, a
      vegetating, ulcerated formation which easily bled was found protruding from the
      right external auditory meatus. Clinical, radiological and pathological features
      of the tumour are described. A subtotal petrosectomy combined with homolateral
      elective lymph node neck dissection was performed. Parotid gland, condyle of the
      mandible and VII cranial nerve were spared since these were free from disease.

PMID- 15952687
TI  - Frontal sinus osteoma complicated by palpebral abscess: case report.
AB  - Osteomas of the paranasal sinuses are slow-growing, benign tumours most
      frequently found in the frontal sinus with an incidence that varies from 47% to
      80% of the cases; there are often no symptoms and they are diagnosed by chance
      during an X-ray examination. When there are symptoms, they are usually headaches
      and ocular or neurological complications. The treatment of choice is surgery. A
      case of frontal osteoma complicated by frontal sinusitis and by a palpebral
      abscess is described.

PMID- 15952689
TI  - State-of-the-art imaging with 64-channel multidetector CT angiography.
AB  - During the past decade, computed tomography angiography (CTA) has become a
      standard noninvasive imaging method for the depiction of vascular anatomy and
      pathology. The quality and speed of CTA examinations have increased dramatically
      as CT technology has evolved from single-channel spiral CT systems (circa 1990)
      to multichannel (4-, 8-, 10-, and 16-slice) spiral CT systems (circa 1998 through
      2001). In 2004, 64-slice multichannel CT technology became available in the
      United States, with the first installation occurring at the Mayo Clinic College
      of Medicine. We describe our initial experience using this state-of-the art
      technology, focusing on examinations that illustrate the increased diagnostic
      resolution of vascular anatomy and pathology, and the effectiveness of 2-and 3
      dimensional postprocessing using a 64-channel CT system. Future applications of
      64-channel technology for preoperative and postoperative vascular surgery and
      endovascular techniques are also described.

PMID- 15952690
TI  - Commentary on "State-of-the-art imaging with 64-channel multidetector CT
      angiography".

PMID- 15952692
TI  - Subintimal angioplasty in the management of critical lower-extremity ischemia:
      value in limb salvage.
AB  - The interest in and overall usage of endovascular procedures for the treatment of
      lower extremity ischemia continues to grow at a rapid pace. An increasing number
      of centers throughout the world are gaining experience with subintimal
      angioplasty. Promising results have been reported and the application of the
      technique has been expanded to include the iliac and crural arteries. The
      technique of subintimal angioplasty and several variations are discussed.
      Although primary patency rates compared with bypass are relatively low for
      patients undergoing subintimal angioplasty, limb salvage rates remain high. When
      a subintimal angioplasty fails, it frequently does so without the recurrence of
      symptoms, especially when a gangrenous lesion or ulcer has healed. Given the many
      advantages of this technique, which include reduced anesthesia requirements, a
      minimally invasive approach, and potential reductions in length of stay and cost,
      subintimal angioplasty will continue to have a role in the treatment of lower
      extremity ischemia. When applied judiciously, bypass options may be preserved.
      This does not, however, mean that the availability of this technique should be
      used as justification to lower the threshold for the treatment.

PMID- 15952693
TI  - Large symptomatic carotid body tumor resection aided by preoperative embolization
      and mandibular subluxation.
AB  - Carotid body tumors (CBT) are rare and usually benign neoplasms (60%-90%),
      originating from the mesoderm and neural ectoderm. In view of the extensive and
      unrelenting growth of unresected CBT, encasing vital neurovascular structures,
      and the significant incidence of malignancy (> or = 10%), surgical excision is
      the standard treatment of choice. Despite progress in CBT imaging and surgical
      technique, cranial nerve deficit, stroke, and death continue to affect 10% to 40%
      of patients undergoing curative surgical resection, particularly in large tumors
      proximal to the skull base. In such cases, CBT shrinkage by preoperative
      embolization, improved surgical access utilizing mandibular subluxation, and
      electroencephalographic monitoring combined with meticulous surgical technique
      may enable curative tumor resection, without prohibitive morbidity. In light of
      associated disability, preoperative acknowledgment of the ever-present
      substantial risk of cranial nerve injury cannot be overemphasized. We report on a
      patient with a large symptomatic CBT treated surgically with the aid of
      mandibular subluxation and preoperative embolization.

PMID- 15952694
TI  - The case for intermittent pneumatic compression of the lower extremity as a novel
      treatment in arterial claudication.
AB  - Appreciation of the physiologic role of the natural muscle pumps of the lower
      limb in enhancing the return of venous blood promoted the development of
      intermittent pneumatic limb compression (IPC) systems that could activate these
      pumps artificially. The application of IPC to the foot (IPC(foot)), calf
      (IPC(calf)) or both (IPC(foot + calf)) on dependency generates a significant
      acute arterial leg inflow enhancement in patients with intermittent claudication
      that is highest with IPC(foot + calf), followed by IPC(calf) and IPC(foot). This
      enhancement is attributable to the leg venous pressure decrease after venous
      expulsion with IPC, which results in arteriovenous pressure elevation, and a
      marked attenuation in peripheral resistance to flow due to a transient abolition
      of peripheral sympathetic autoregulation and the release of nitric oxide.
      Implementation of IPC(foot) and IPC(foot + calf) for 3 to 5 months (> or = 2.5
      hours/day) has been shown to improve the walking capacity and the ankle pressure
      indices of patients with intermittent claudication, with a significant beneficial
      impact on the quality of life. As the prevalence of symptomatic peripheral
      arterial disease is projected to increase substantially over the next decades
      with the aging population in Western societies and in the absence of established,
      cost-effective methods of treatment for claudication, the reported efficacy of
      IPC in claudication certainly warrants clinical attention. Level-1 clinical
      evidence by three independent investigators supports the clinical role of IPC in
      arterial claudication, reinforced by its domiciliary applicability, the high
      patient compliance with which it is associated, and the modest cost. This review
      offers an insight into the hemodynamic and clinical effects of IPC in patients
      with claudication in relation to the physiologic mechanisms proposed in
      explanation of these effects.

PMID- 15952695
TI  - Superficial vein thrombosis and hypercoagulable states: the evidence.
AB  - AIM: To assess the demographic features of superficial vein thrombosis and its
      relation with the occurrence of hypercoagulable states. METHODS: Data were
      gathered from pertinent papers using a MEDLINE search and an exhaustive
      bibliography review. Studies were considered only when they contained material to
      superficial vein thrombosis and hypercoagulable states. RESULTS: The difference
      among the patients and the methods used made the comparison difficult and did not
      allow a pool analysis of the data. Superficial vein thrombosis is a common
      condition, and its prevalence is underestimated. Several risk factors are
      associated with superficial vein thrombosis, and a strong relation was seen with
      certain thrombophilias. CONCLUSIONS: Although superficial vein thrombosis most
      often is perceived as benign, it can coexist with hypercoagulable states. In
      patients with spontaneous onset of superficial vein thrombosis, there should be a
      lower threshold in testing for hypercoagulable states.

PMID- 15952696
TI  - Endovascular procedures, carotid endarterectomies, and aortic surgery should
      preferentially be done by a vascular trainee rather than a general surgery
      resident.
AB  - This article is the result of a debate. The motion proposed was that
      "endovascular procedures, carotid endarterectomies, and aortic surgery should be
      done preferentially by a vascular trainee rather than a general surgery
      resident.'' Arguments in favor of the motion were that with the development of
      endovascular surgery, there are now less open vascular procedures to perform and
      hence, vascular trainees needed to hone their skills on these limited cases
      rather than waste that experience on a general surgery resident. This focused
      training experience would allow vascular fellows to be become more highly skilled
      vascular surgeons. Additionally, endovascular procedures are an important
      component of modern vascular surgery, and it is important for the vascular fellow
      to develop significant experience with and acquire the appropriate numbers of
      endovascular cases to get the necessary credentials when going into a vascular
      practice. Arguments against the motion were that exposure to vascular cases will
      make a better general surgeon, one who will also be well equipped to deal with
      trauma cases and situations where the control of bleeding might be life saving.
      Additionally, the issue of exposure of general surgery residents to vascular
      cases might be a positive recruitment strategy for future vascular fellows. The
      motion was carried by a small majority vote.

PMID- 15952698
TI  - Commentary. Characterization of carotid artery plaques using real-time compound B
      mode ultrasound.

PMID- 15952699
TI  - Commentary. Circulating monocytes and in-stent neointima after coronary stent
      implantation.

PMID- 15952701
TI  - Commentary. Prevention of disabling and fatal strokes by successful carotid
      endarterectomy in patients without recent neurological symptoms: randomized
      controlled trial.

PMID- 15952703
TI  - Commentary. Carotid angioplasty and stenting versus carotid endarterectomy for
      treatment of asymptomatic carotid stenosis: a randomized trial in a community
      hospital.

PMID- 15952705
TI  - Commentary. DWI abnormalities and clinical characteristics in TIA patients.

PMID- 15952709
TI  - Commentary. Effect of clonidine on cardiovascular morbidity and mortality after
      noncardiac surgery.

PMID- 15952708
TI  - Commentary. Additive benefits of pravastatin and aspirin to decrease risks of
      cardiovascular disease: randomized and observational comparisons of secondary
      prevention trials and their meta-analyses.

PMID- 15952712
TI  - Commentary. De novo femoropopliteal stenoses: endovascular gamma irradiation
      following angioplasty--angiographic and clinical follow-up in a prospective
      randomized controlled trial.

PMID- 15952713
TI  - Infrared mass spectrometric imaging below the diffraction limit.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)1 is an
      established technique for the analysis of biological macromolecules. Its relative
      insensitivity to pollutants makes MALDI-MS very suitable for the direct analysis
      of biological samples. As such, it has facilitated great advances in the field of
      biomolecular imaging mass spectrometry. Traditionally, MALDI-MS imaging is
      performed in a scanning microprobe methodology.(2-4) However, in a recent study
      we have demonstrated an alternative methodology; the so-called microscope
      mode,(5) where the requirement for a highly focused ionization beam is removed.
      Spatial details from within the desorption area are conserved during the flight
      of the ions through the mass analyzer, and a magnified ion image is projected
      onto a 2D-detector. In this paper, we demonstrate how imaging mass spectrometry
      benefits from the microscope mode approach. For the first time, high-lateral
      resolution ion images were recorded using infrared MALDI at 2.94 microm
      wavelength. The ion optical resolution achieved was well below the theoretical
      limit of (light-) diffraction for the setup used, which is impossible to achieve
      in the conventional scanning microprobe approach.

PMID- 15952714
TI  - Global protein shotgun expression profiling of proliferating mcf-7 breast cancer
      cells.
AB  - Protein expression becomes altered in breast epithelium during malignant
      transformation. Knowledge of these perturbations should provide insight into the
      molecular basis of breast cancer, as well as reveal possible new therapeutic
      targets. To this end, we have performed an extensive comparative proteomic survey
      of global protein expression patterns in proliferating MCF-7 breast cancer cells
      and normal human mammary epithelial cells using gel-free shotgun tandem mass
      spectrometry. Pathophysiological alterations associated with the malignant breast
      cancer phenotype were detected, including differences in the apparent levels of
      key regulators of the cell cycle, signal transduction, apoptosis, transcriptional
      regulation, and cell metabolism.

PMID- 15952715
TI  - MultiProtIdent: identifying proteins using database search and protein-protein
      interactions.
AB  - Protein identification is important in proteomics. Proteomic analyses based on
      mass spectra (MS) constitute innovative ways to identify the components of
      protein complexes. Instruments can obtain the mass spectrum to an accuracy of
      0.01 Da or better, but identification errors are inevitable. This study shows a
      novel tool, MultiProtIdent, which can identify proteins using additional
      information about protein-protein interactions and protein functional
      associations. Both single and multiple Peptide Mass Fingerprints (PMFs) are input
      to MultiProtIdent, which matches the PMFs to a theoretical peptide mass database.
      The relationships or interactions among proteins are considered to reduce false
      positives in PMF matching. Experiments to identify protein complexes reveal that
      MultiProtIdent is highly promising. The website associated with this study is
      http://dbms104.csie.ncu.edu.tw/.

PMID- 15952716
TI  - Proteomic studies on low- and high-grade human brain astrocytomas.
AB  - Human brain astrocytomas range from the indolent low-grade to the highly
      infiltrating and aggressive high-grade form, also known as glioblastoma
      multiforme. The extensive heterogeneity of astrocytic tumors complicates their
      pathological classification. In this study, we compared the protein pattern of
      low-grade fibrillary astrocytomas to that of glioblastoma multiforme by 2D
      electrophoresis. The level of most proteins remains unchanged between the
      different grade tumors and only few differences are reproducibly observable.
      Fifteen differentially expressed proteins, as well as seventy conserved spots,
      were identified by mass spectrometry. Western and immnunohistochemical analysis
      confirmed the differential expression of the identified proteins. These data
      provide an initial reference map for brain gliomas. Among the proteins more
      highly expressed in glioblastoma multiforme, we found peroxiredoxin 1 and 6, the
      transcription factor BTF3, and alpha-B-crystallin, whereas protein disulfide
      isomerase A3, the catalytic subunit of the cAMP-dependent protein kinase, and the
      glial fibrillary acidic protein are increased in low-grade astrocytomas. Our
      findings contribute to deepening our knowledge of the factors that characterize
      this class of tumors and, at the same time, can be applied toward the development
      of novel molecular biomakers potentially useful for an accurate classification of
      the grade of astrocytomas.

PMID- 15952717
TI  - Global whole-cell FTICR mass spectrometric proteomics analysis of the heat shock
      response in the radioresistant bacterium Deinococcus radiodurans.
AB  - The results of previous studies indicated that D. radiodurans mounts a regulated
      protective response to heat shock, and that expression of more than 130 genes,
      including classical chaperones such as the groESL and dnaKJ operons and proteases
      such as clpB are induced in response to elevated temperature. In addition,
      previous qualitative whole-cell mass spectrometric studies conducted under heat
      shock conditions indicated global changes in the D. radiodurans proteome. To
      enable the discovery of novel heat shock inducible proteins as well as gain
      greater biological insight into the classical heat shock response at the protein
      level, we undertook the global whole-cell FTICR mass spectrometric proteomics
      study reported here. We have greatly increased the power of this approach by
      conducting a large number of replicate experiments in addition to taking a
      semiquantitative approach to data analysis, finding good reproducibility between
      replicates. Through this analysis, we have identified with high confidence a core
      set of classical heat shock proteins whose expression increases dramatically and
      reproducibly in response to elevated temperature. In addition, we have found that
      the heat shock proteome includes a large number of induced proteins that have not
      been identified previously as heat responsive, and have therefore been designated
      as candidate responders. Finally, our results are consistent with the hypothesis
      that elevated temperature stress could lead to cross-protection against other
      related stresses.

PMID- 15952718
TI  - Comparative analysis of the tear protein expression in blepharitis patients using
      two-dimensional electrophoresis.
AB  - Change in the expression of body fluid proteins is caused by many diseases or
      environmental disturbances. The changes in tear proteins are also associated with
      various pathological eye conditions. Especially, chronic blepharitis is one of
      the most common conditions seen in the ophthalmologist's office. However, there
      are no specific clinical diagnostic tests for blepharitis, and it is difficult to
      treat effectively. Therefore, the aim of this study was to screen prognostic or
      diagnostic marker tear proteins for blepharitis and investigate pathogenesis of
      this disease using proteomics techniques. The tear proteins expressed in patients
      suffering from blepharitis (patient, n=19) and healthy volunteers (control, n=27)
      were analyzed using the two-dimensional electrophoresis (2-DE) technique. The
      differentially expressed proteins in patients were identified with ESI-Q-TOF
      (electrospray-quadrupole-time-of-flight) mass spectrometry and confirmed with
      western blotting. Nine proteins in patient were down regulated about 50% compared
      to those of the control: serum albumin precursor, alpha-1 antitrypsin, lacritin
      precursor, lysozyme, Ig-kappa chain VIII, prolactin inducible protein (PIP/GCDFP
      15), cystatin-SA III, pyruvate kinase, and an unnamed protein. The use of the two
      dimensional eletrophoretic technique could give more insight into the disease
      related protein expression changes in tear fluids. Our findings reveal that the
      composition of tear proteins in blepharitis patients is different from that of
      healthy subjects and may provide further insights into the pathogenesis of
      blepharitis.

PMID- 15952719
TI  - Organelle proteomics of rat synaptic proteins: correlation-profiling by isotope
      coded affinity tagging in conjunction with liquid chromatography-tandem mass
      spectrometry to reveal post-synaptic density specific proteins.
AB  - Organelle proteomics is the method of choice for global analysis of cellular
      proteins. However, it is difficult to isolate organelles to homogeneity.
      Recently, correlation-profiling has been used to filter off the contaminants ad
      hoc and to disclose the genuine organelle-specific proteins. In the present
      study, we further extend the method to include subcellular compartments that
      contain proteins shared by multiple distinct subcellular domains. We performed
      correlation profiling of proteins contained in synaptic membrane and postsynaptic
      density (PSD) fractions isolated from rat brain. Proteins were labeled with
      isotope-coded affinity-tag reagents, digested with trypsin, and resulting
      peptides were resolved by cation exchange chromatography followed by reversed
      phase chromatography. Peptides were then subjected to mass spectrometry for
      quantification and identification. We confirm that the core PSD proteins were
      enriched in the PSD preparation. Other functional protein groups such as
      cytoskeleton-associated proteins, protein kinases and phosphatases, signaling
      components and regulators, as well as proteins involved in energy production
      partitioned to multiple organelles. When analyzed as groups, they were shown to
      accumulate to a lesser extent. Mitochondrial proteins and transporters were
      generally strongly depleted from the PSD fraction confirming that they were
      contaminants of the PSD preparation. Finally, immunoelectron microscopy was
      performed on selected proteins to validate the proteomics results, and confirm
      that synaptophysin that was highly depleted in the PSD preparation is localized
      in the presynaptic compartment, whereas LASP-1 that was slightly enriched in the
      PSD preparation is present in the PSD as well as other subdomains within the
      synapse.

PMID- 15952720
TI  - Quantitative proteome analysis using differential stable isotopic labeling and
      microbore LC-MALDI MS and MS/MS.
AB  - We demonstrate an approach for global quantitative analysis of protein mixtures
      using differential stable isotopic labeling of the enzyme-digested peptides
      combined with microbore liquid chromatography (LC) matrix-assisted laser
      desorption ionization (MALDI) mass spectrometry (MS). Microbore LC provides
      higher sample loading, compared to capillary LC, which facilitates the
      quantification of low abundance proteins in protein mixtures. In this work,
      microbore LC is combined with MALDI MS via a heated droplet interface. The
      compatibilities of two global peptide labeling methods (i.e., esterification to
      carboxylic groups and dimethylation to amine groups of peptides) with this LC
      MALDI technique are evaluated. Using a quadrupole-time-of-flight mass
      spectrometer, MALDI spectra of the peptides in individual sample spots are
      obtained to determine the abundance ratio among pairs of differential
      isotopically labeled peptides. MS/MS spectra are subsequently obtained from the
      peptide pairs showing significant abundance differences to determine the
      sequences of selected peptides for protein identification. The peptide sequences
      determined from MS/MS database search are confirmed by using the overlaid
      fragment ion spectra generated from a pair of differentially labeled peptides.
      The effectiveness of this microbore LC-MALDI approach is demonstrated in the
      quantification and identification of peptides from a mixture of standard proteins
      as well as E. coli whole cell extract of known relative concentrations. It is
      shown that this approach provides a facile and economical means of comparing
      relative protein abundances from two proteome samples.

PMID- 15952721
TI  - Direct MS/MS analysis of proteins blotted on membranes by a matrix-assisted laser
      desorption/ionization-quadrupole ion trap-time-of-flight tandem mass
      spectrometer.
AB  - We constructed a system for the microscale identification of membrane-blotted
      proteins by proteolytic digestion using an instrument developed with
      piezoelectric chemical inkjet technology and MS/MS analyses of the resulting
      peptides with a matrix-assisted laser desorption/ionization-quadrupole ion trap
      time-of-flight tandem mass spectrometer (MALDI-QIT-TOF MS). Using this system,
      bovine serum albumin was clearly identified at levels less than 100 fmol, and
      proteins from an Escherichia coli extract were also identified by an MS/MS ion
      search.

PMID- 15952722
TI  - Proteomic profiling of erythrocyte proteins by proteolytic digestion chip and
      identification using two-dimensional electrospray ionization tandem mass
      spectrometry.
AB  - Self-assembled monolayers (SAMs) on coinage metal provide versatile modeling
      systems for studies of interfacial electron transfer, biological interactions,
      molecular recognition, and other interfacial phenomena. The bonding of enzyme to
      SAMs of alkanethiols onto gold surfaces is exploited to produce an enzyme chip.
      In this work, the attachment of trypsin to a SAMs surface of 11
      mercaptoundecanoic acid was achieved using water soluble N-ethyl-N'-(3
      dimethylaminopropyl) carbodiimide hydrochloride and N-hydroxysuccinimide as
      coupling agent. A two-dimensional liquid-phase separation scheme coupled with
      mass spectrometry is presented for proteomic analysis of erythrocyte proteins.
      The application of proteomics, particularly with reference to analysis of
      proteins, will be described. Surface analyses have revealed that the X-ray
      Photoelectron Spectroscopy (XPS) C1s and N1s core levels illustrate the
      immobilization of trypsin. These data are also in good agreement with Fourier
      Transformed Infrared Reflection-Attenuated Total Reflection (FTIR-ATR) spectra
      for the peaks at Amide I and Amide II. Using two-dimensional nano-high
      performance liquid chromatography electrospray ionization tandem mass
      spectrometry (2D nano-HPLC-ESI-MS/MS) system observations, analytical results
      have demonstrated the erythrocyte proteins digestion of the immobilized trypsin
      on the functionalized SAMs surface. For such surfaces, it also shows the enzyme
      digestion ability of the immobilized trypsin. The experiment results revealed the
      identification of 272 proteins from erythrocyte protein sample. The terminal
      groups of the SAMs structure can be further functionalized with biomolecules or
      antibodies to develop surface-base diagnostics, biosensors, or biomaterials.

PMID- 15952723
TI  - Determination of relative protein abundance by internally normalized ratio
      algorithm with antibody arrays.
AB  - In this paper, we report an experimental setup and mathematical algorithm for
      determination of relative protein abundance from directly labeled native protein
      samples applied to an array of antibodies. The application of the proposed
      experimental system compensates internally at each array element for a number of
      deficiencies in array experiments such as differential labeling efficiency in
      dual color assay systems, differential solubility of protein molecules in dual
      color assay systems, and differential affinity of capture reagents toward
      proteins labeled with two different fluorescent dyes. This system offers full
      compensation for variable amounts of capture reagents on separate array
      structures, as well as limited compensation for nonspecific interactions between
      capture reagents and analytes. The proposed experimental strategy enables the use
      of a large number of capture reagents to develop a true multiplex analysis system
      that will yield complete relative protein abundance information in two biological
      systems.

PMID- 15952724
TI  - Proteome analysis of primary neurons and astrocytes from rat cerebellum.
AB  - Neurons and astrocytes are predominant cell types in brain and have distinguished
      morphological and functional features. Although several proteomics studies were
      carried out on the brain, work on individual brain cells is limited. Generating
      individual proteomes of neurons and astrocytes, however, is mandatory to assign
      protein expression to cell types rather than to tissues. We aimed to provide maps
      of rat primary neurons and astrocytes using two-dimensional gel electrophoresis
      with subsequent in-gel digestion, followed by MALDI-TOF/TOF. 428 protein spots
      corresponding to 226 individual proteins in neurons and 406 protein spots
      representing 228 proteins in astrocytes were unambiguously identified. Proteome
      data include proteins from several cascades differentially expressed in neurons
      and astrocytes, and specific expressional patterns of antioxidant, signaling,
      chaperone, cytoskeleton, nucleic acid binding, proteasomal, and metabolic
      proteins are demonstrated. We herein present a reference database of primary rat
      primary neuron and astrocyte proteomes and provide an analytical tool for these
      structures. The concomitant expressional patterns of several protein classes are
      given and potential neuronal and astrocytic marker candidates are presented.

PMID- 15952725
TI  - Study of ligand-receptor binding using SPME: investigation of receptor, free, and
      total ligand concentrations.
AB  - The theoretical background and practical approaches for studying ligand-receptor
      (protein) binding by solid phase microextraction (SPME) are investigated, along
      with methods for simultaneous calculation of receptor, free, and total ligand
      concentrations. With the introduction of new extraction phases (restricted access
      materials, molecularly imprinted polymers, and immobilized antibodies), SPME
      allows better separation of small molecules of ligand from larger molecules of
      receptor, and improved accuracy. This sample preparation method based on
      nonexhaustive extraction is well suited as a general method to study and quantify
      systems involving multiple equilibriums, with significant advantages over
      currently used methods. SPME was used previously for the determination of protein
      binding constants, but only with conventional extraction phases and in simple
      cases, with a 1:1 combination ratio between the ligand and the receptor or when
      negligible depletion conditions were met. The new theoretical approach presented
      in this study allows the quantification of any binding equilibrium, regardless of
      the extent of depletion. Restricted-access particles are used as extraction
      phase, and if the amount of receptor is limited, selected regions of the binding
      curve may be obtained using a single sample, with a volume as low as 10 muL. The
      equations developed here are simple and independent of the analytical method used
      for the quantification of the amount of ligand. Three different practical
      approaches are presented: the method of multiple standard solutions, the method
      of successive extractions from the same sample and the method of successive
      additions to the same sample. The usefulness of this novel approach is
      demonstrated by using it to determine the binding parameters of some selected
      drugs to human serum albumin. These parameters are subsequently used to calculate
      albumin, free drug, and total drug concentrations from unknown mixtures. The
      results are in good agreement with previously published data. Quantification of
      the amount of ligand extracted by SPME is done by liquid chromatography coupled
      with tandem mass spectrometry.

PMID- 15952726
TI  - Global proteome discovery using an online three-dimensional LC-MS/MS.
AB  - We have developed a proteomics technology featuring on-line three-dimensional
      liquid chromatography coupled to tandem mass spectrometry (3D LC-MS/MS). Using 3D
      LC-MS/MS, the yeast-soluble, urea-solubilized peripheral membrane and SDS
      solubilized membrane protein samples collectively yielded 3019 unique yeast
      protein identifications with an average of 5.5 peptides per protein from the 6300
      gene Saccharomyces Genome Database searched with SEQUEST. A single run of the
      urea-solubilized sample yielded 2255 unique protein identifications, suggesting
      high peak capacity and resolving power of 3D LC-MS/MS. After precipitation of SDS
      from the digested membrane protein sample, 3D LC-MS/MS allowed the analysis of
      membrane proteins. Among 1221 proteins containing two or more predicted
      transmembrane domains, 495 such proteins were identified. The improved yeast
      proteome data allowed the mapping of many metabolic pathways and functional
      categories. The 3D LC-MS/MS technology provides a suitable tool for global
      proteome discovery.

PMID- 15952727
TI  - Optimal replication and the importance of experimental design for gel-based
      quantitative proteomics.
AB  - Quantitative proteomic studies, based on two-dimensional gel electrophoresis, are
      commonly used to find proteins that are differentially expressed between samples
      or groups of samples. These proteins are of interest as potential diagnostic or
      prognostic biomarkers, or as proteins associated with a trait. The complexity of
      proteomic data poses many challenges, so while experiments may reveal proteins
      that are differentially expressed, these are often not significant when subjected
      to rigorous statistical analysis. However, this can be addressed through
      appropriate experimental design. A good experimental design considers the impact
      of different sources of variation, both analytical and biological, on the
      statistical importance of the results. The design should address the number of
      samples that must be analyzed and the number of replicate gels per sample, in the
      context of a particular minimum difference that one is seeking to achieve. In
      this study, we explore the ways to improve the quality of protein expression data
      from 2-DE gels, and describe an approach for defining the number of samples
      required and the number of gels per sample. It has been developed for the
      simplest of situations, two groups of samples with variation at two levels:
      between samples and between gels. This approach will also be useful as a guide
      for more complex designs involving more than two groups of samples. We describe
      some Internet-accessible tools that can assist in the design of proteomic
      studies.

PMID- 15952728
TI  - Diagnostic potential of tear proteomic patterns in Sjogren's syndrome.
AB  - Histological and functional changes of the lacrimal gland might be reflected in
      proteomic patterns in tear fluids. In this study, we carried out a determination
      of the disease biomarkers in tear fluid for Sjogren's syndrome (SS) and a
      performance of noninvasive diagnostic test based on the proteomic patterns.
      Thirty-one SS patients and 57 control subjects were enrolled to this study. Their
      details were 23 cases with primary SS, 8 with secondary SS, 14 with dry eyes, 22
      with miscellaneous ocular diseases, and 21 of healthy volunteers. Protein
      profiling in tear fluids was identified by surface enhanced laser
      desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Multiple
      protein changes were reproducibly detected in the primary SS group, including 10
      potential novel biomarkers. Seven of the biomarkers (2094, 2743, 14191, 14702,
      16429, 17453, 17792 m/z) were down-regulated and 3 biomarkers (3483, 4972, 10860
      m/z) were up-regulated in primary SS group, comparing to the protein profiles of
      control subjects. When cutoff value of SS down-score was set less than 0.5, this
      result yielded 87% sensitivity and 100% specificity. The positive predictive
      value for this sample set was 100%. There was a significant inverse correlation
      between SS down-scores and epithelial damages of the ocular surface in primary SS
      patients. These findings support the potential of proteomic pattern technology in
      tear fluids as the noninvasive diagnostic test for primary SS.

PMID- 15952729
TI  - Quantitation of de novo localized (15)N-labeled lipoproteins and membrane
      proteins having one and two transmembrane segments in a Bacillus subtilis secA
      temperature-sensitive mutant using 2D-PAGE and MALDI-TOF MS.
AB  - We developed a means of quantifying proteins that have just localized in the
      cytoplasmic membrane using 15N-whole cell labeling together with 2D-PAGE and
      MALDI-TOF MS. The localization of 18 among 20 proteins consisting of 8
      lipoproteins, 11 integral membrane proteins having one or two transmembrane
      segments and one secretory protein in the membrane fractions of Bacillus
      subtilis, was inhibited by the absence of SecA in a temperature-sensitive mutant.
      The time course of inhibition indicated that SecA participates in the
      localization of those proteins through immediately dependent, delayed dependent,
      and independent ways.

PMID- 15952730
TI  - Evaluation of protein depletion methods for the analysis of total-, phospho- and
      glycoproteins in lumbar cerebrospinal fluid.
AB  - A proper sample preparation, in particular, abundant protein removal is crucial
      in the characterization of low-abundance proteins including those harboring post
      translational modifications. In human cerebrospinal fluid (CSF), approximately
      80% of proteins originate from serum, and removal of major proteins is necessary
      to study brain-derived proteins that are present at low concentrations for
      successful biomarker and therapeutic target discoveries for neurological
      disorders. In this study, phospho- and glycoprotein specific fluorescent stains
      and mass spectrometry were used to map proteins from CSF on two-dimensional gel
      electropherograms after immunoaffinity based protein removal. Two protein removal
      methods were evaluated: batch mode with avian IgY antibody microbeads using spin
      filters and HPLC multiple affinity removal column. Six abundant proteins were
      removed from CSF: human serum albumin (HSA), transferrin, IgG, IgA, IgM, and
      fibrinogen with batch mode, and HSA, transferrin, IgG, IgA, antitrypsin, and
      haptoglobin with column chromatography. 2D gels were compared after staining for
      phospho-, glyco- and total proteins. The column format removed the major proteins
      more effectively and approximately 50% more spots were visualized when compared
      to the 2D gel of CSF without protein depletion. After protein depletion, selected
      phospho- and glycoprotein spots were identified using mass spectrometry in
      addition to some of the spots that were not visualized previously in nondepleted
      CSF. Fifty proteins were identified from 66 spots, and among them, 12 proteins
      (24%) have not been annotated in previously published 2D gels.

PMID- 15952731
TI  - Characterization of purified c-type heme-containing peptides and identification
      of c-type heme-attachment sites in Shewanella oneidenis cytochromes using mass
      spectrometry.
AB  - We describe methods for mass spectrometric identification of heme-containing
      peptides from c-type cytochromes that contain the CXXCH (X=any amino acid)
      sequence motif. The heme fragment ion yielded the most abundant MS/MS peak for
      standard heme-containing peptides with one amino acid difference for both 2+ and
      3+ peptide charge states; both sequence and charge affect the extent of heme
      loss. Application to Shewanella oneidenis demonstrated the utility of this
      approach for identifying c-type heme-containing peptides from complex proteome
      samples.

PMID- 15952732
TI  - Identification of Mycobacterium tuberculosis H37Rv integral membrane proteins by
      one-dimensional gel electrophoresis and liquid chromatography electrospray
      ionization tandem mass spectrometry.
AB  - Because many membrane-associated proteins represent potential drug targets,
      diagnostic probes, and components of vaccines, we have chosen to study the
      membrane proteins of Mycobacterium tuberculosis H37Rv. To remove cytosolic
      proteins and facilitate access to the integral membrane proteins, membrane
      fractions of M. tuberculosis H37Rv were intensely washed with 5 M urea and high
      pH carbonate solution. One-dimensional SDS-PAGE, followed by enzymatic hydrolysis
      and nanoLC electrospray ionization MS/MS, proved to be the most efficient way to
      identify the proteins contained within the membrane fraction. Here we report 349
      protein identifications in total, validated by at least two tryptic peptide
      matches and MOWSE scores greater than 75. Of those 349 proteins, 100 are integral
      membrane proteins with at least one predicted transmembrane alpha helix
      (excluding the possible signal sequence). 84 M. tuberculosis H37Rv proteins,
      including 42 integral membrane proteins, are described for the first time.

PMID- 15952733
TI  - Sequence similarity-based proteomics in insects: characterization of the larvae
      venom of the Brazilian moth Cerodirphia speciosa.
AB  - Using a combination of tandem mass spectrometric sequencing and sequence
      similarity searches, we characterized the larvae venom of the moth Cerodirphia
      speciosa, which belongs to the Saturniidae family of the Lepidoptera order.
      Despite the paucity of available database sequence resources, the approach
      enabled us to identify 48 out of 58 attempted spots on its two-dimensional gel
      electrophoresis map, which represented 37 unique proteins, whereas it was only
      possible to identify 13 proteins by conventional non-error tolerant database
      searching methods. The majority of cross-species hits were made to proteins from
      the phylogenetically related Lepidoptera organism, the silk worm Bombyx mori. The
      protein composition of the venom suggested that envenoming by C. speciosa toxins
      might proceed through the contact with its hemolymph, similarly to another toxic
      Lepidoptera organism, Lonomia obliqua.

PMID- 15952734
TI  - Differential expression of proteins in response to ceramide-mediated stress
      signal in colon cancer cells by 2-D gel electrophoresis and MALDI-TOF-MS.
AB  - Comparative cancer cell proteome analysis is a strategy to study the implication
      of ceramides in the transmission of stress signals. To better understand the
      mechanisms by which ceramide regulate some physiological or pathological events
      and the response to the pharmacological treatment of cancer, we performed a
      differential analysis of the proteome of HCT-116 (human colon carcinoma) cells in
      response to these substances. We first established the first 2-dimensional map of
      the HCT-116 proteome. Then, HCT116 cell proteome treated or not with C6-ceramide
      have been compared using two-dimensional electrophoresis, matrix-assisted laser
      desorption/ionization-mass spectrometry and bioinformatic (genomic databases). 2
      DE gel analysis revealed more than fourty proteins that were differentially
      expressed in control cells and cells treated with ceramide. Among them, we
      confirmed the differential expression of proteins involved in apoptosis and cell
      adhesion.

PMID- 15952735
TI  - Comparative analysis of the ADAM and ADAMTS families.
AB  - The "A Disintegrin And Metalloproteinase" (ADAM) protein family and the "A
      Disintegrin-like And Metalloproteinase with ThromboSpondin motifs" (ADAMTS)
      protein family are two related families of human proteins. The similarities and
      differences between these two families have been investigated using phylogenetic
      trees and homology modeling. The phylogenetic analysis indicates that the two
      families are well differentiated, even when only the common metalloprotease
      domain is taken into account. Within the ADAM family, several proteins are
      lacking the binding motif for the catalytic zinc in the active site and thus
      presumably lack any catalytic activity. These proteins tend to cluster within the
      ADAM phylogenetic tree and are expressed in specific tissues, suggesting a
      functional differentiation. The present analysis allows us to propose the
      following: (i) ADAMTS proteins have a conserved role in the human organism as
      proteases, with some differentiation in terms of substrate specificity; (ii) ADAM
      proteins can act as proteases and/or mediators of intermolecular interactions;
      (iii) proteolytically active ADAMs tend to be more ubiquitously expressed than
      the inactive ones.

PMID- 15952736
TI  - Afamin is a novel human vitamin E-binding glycoprotein characterization and in
      vitro expression.
AB  - Hydrophobic vitamins are transported in human plasma and extravascular fluids by
      carrier proteins. No specific protein has been described so far for vitamin E,
      which plays a crucial role in protecting against oxidative damage and disease. We
      report here the purification of a 75-kDa glycoprotein with vitamin E-binding
      properties by stepwise chromatography of lipoprotein-depleted human plasma and
      monitoring of vitamin E (alpha-tocopherol)-binding activity. Partial sequencing
      identified this protein as afamin, a previously described member of the albumin
      gene family with four or five potential N-glycosylation sites. Glycosylation
      analysis indicated that >90% of the glycans were sialylated biantennary complex
      structures. The vitamin E-binding properties were confirmed using recombinantly
      expressed afamin. Qualitative and quantitative analysis of plasma and
      extravascular fluids revealed an abundant presence of this protein not only in
      plasma (59.8+/-13.3 microg/mL) but also in extravascular fluids such as
      follicular (34.4+/-12.7 microg/mL) and cerebrospinal (0.28+/-0.16 microg/mL)
      fluids, suggesting potential roles for afamin in fertility and neuroprotection.
      Afamin is partly (13%) bound to plasma lipoproteins. Afamin and vitamin E
      concentrations significantly correlate in follicular and cerebrospinal fluids but
      not in plasma. The vitamin E association of afamin in follicular fluid was
      directly demonstrated by gel filtration chromatography and immunoprecipitation
      which complements the in vitro findings for purified native and recombinant
      afamin.

PMID- 15952737
TI  - Integrative proteomics: functional and molecular characterization of a particular
      glutamate-related neuregulin isoform.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian brain and is
      related to memory by calcium-conducting receptors. Neuregulins have emerged as
      long-term modulating molecules of synaptic signaling by glutamate receptors,
      playing a role in some cognition/memory-related disorders and moreover being part
      of transient functional microdomains, called lipid rafts. Here we characterize
      one specific isoform of neuregulin as a central biomarker for glutamate-related
      signaling, integrating results from in vitro and in vivo models by a differential
      functional and proteomic approach.

PMID- 15952738
TI  - Robust method for proteome analysis by MS/MS using an entire translated genome:
      demonstration on the ciliome of Tetrahymena thermophila.
AB  - To improve the utility of increasingly large numbers of available unannotated and
      initially poorly annotated genomic sequences for proteome analysis, we
      demonstrate that effective protein identification can be made on a large and
      unannotated genome. The strategy developed is to translate the unannotated genome
      sequence into amino acid sequence encoding putative proteins in all six reading
      frames, to identify peptides by tandem mass spectrometry (MS/MS), to localize
      them on the genome sequence, and to preliminarily annotate the protein via a
      similarity search by BLAST. These tasks have been optimized and automated.
      Optimization to obtain multiple peptide matches in effect extends the searchable
      region and results in more robust protein identification. The viability of this
      strategy is demonstrated with the identification of 223 cilia proteins in the
      unicellular eukaryotic model organism Tetrahymena thermophila, whose initial
      genomic sequence draft was released in November 2003. To the best of our
      knowledge, this is the first demonstration of large-scale protein identification
      based on such a large, unannotated genome. Of the 223 cilia proteins, 84 have no
      similarity to proteins in NCBI's nonredundant (nr) database. This methodology
      allows identifying the locations of the genes encoding these novel proteins,
      which is a necessary first step to downstream functional genomic experimentation.

PMID- 15952739
TI  - Differential protein expression profiles of gastric epithelial cells following
      Helicobacter pylori infection using ProteinChips.
AB  - Helicobacter pylori infects approximately half of the world's population and the
      bacterium is associated with gastric cancer and peptic and duodenal ulcers. In
      this study, Surface Enhanced Laser Desorption /Ionization time-of-flight mass
      spectrometry (SELDI-TOF-MS) was used to identify the biomarkers from H. pylori
      infected gastric epithelial cells (GEC) to understand key mechanisms associated
      with pathogenesis. Using different chip surfaces, differential protein expression
      profile of GEC was obtained and several upregulated or downregulated biomarkers
      were detected on GEC, following H. pylori infection. Four different H. pylori
      infected GECs were compared based on their expression of MHC class II, a receptor
      reported to trigger apoptosis. One biomarker was identified in H. pylori infected
      GEC as Annexin A2 (Annexin II) from the flow through of the anion-exchange resin.
      The increased expression of Annexin II in GEC following H. pylori infection was
      further confirmed by Western Blot analyses and indicates its involvement in H.
      pylori pathogenesis.

PMID- 15952740
TI  - Protein profiling of human pancreatic islets by two-dimensional gel
      electrophoresis and mass spectrometry.
AB  - Completion of the human genome sequence has provided scientists with powerful
      resources with which to explore the molecular events associated with disease
      states such as diabetes. Understanding the relative levels of expression of gene
      products, especially of proteins, and their post-translational modifications will
      be critical. However, though the pancreatic islets play a key role in glucose
      homeostasis, global protein expression data in human are decidedly lacking. We
      here report the two-dimensional protein map and database of human pancreatic
      islets. A high level of reproducibility was obtained among the gels and a total
      of 744 protein spots were detected. We have successfully identified 130 spots
      corresponding to 66 different protein entries and generated a reference map of
      human islets. The functionally characterized proteins include enzymes,
      chaperones, cellular structural proteins, cellular defense proteins, signaling
      molecules, and transport proteins. A number of proteins identified in this study
      (e.g., annexin A2, elongation factor 1-alpha 2, histone H2B.a/g/k, heat shock
      protein 90 beta, heat shock 27 kDa protein, cyclophilin B, peroxiredoxin 4,
      cytokeratins 7, 18, and 19) have not been previously described in the database of
      mouse pancreatic islets. In addition, altered expression of several proteins,
      like GRP78, GRP94, PDI, calreticulin, annexin, cytokeratins, profilin, heat shock
      proteins, and ORP150 have been associated with the development of diabetes. The
      data presented in this study provides a first-draft reference map of the human
      islet proteome, that will pave the way for further proteome analysis of
      pancreatic islets in both healthy and diabetic individuals, generating insights
      into the pathophysiology of this condition.

PMID- 15952741
TI  - In vivo dual-tagging proteomic approach in studying signaling pathways in immune
      response.
AB  - Up to date, few successes have been achieved to identify the signaling molecules
      directly from immune cells due to their low-abundance and dynamic nature. Here,
      we designed an in vivo dual-tagging quantitative approach that integrated epitope
      tagging which allows single affinity purification of the natural complexes formed
      at real-time, and amino acid-coded mass tagging (AACT) that assists mass
      spectrometry-based quantitative measurement, to identify the specific components
      of a signaling complex formed in macrophage cells upon lipopolysaccharide (LPS)
      stimulation. The sensitivity and accuracy of this quantitative method are
      significantly higher than those of tandem affinity purification, because the
      multiple step of purifications are avoided to preserve weakly interacting
      molecules. We identified a number of proteins that interact with MyD88, a
      critical adaptor protein in innate immune response, in macrophages upon
      stimulation. Among those newly identified MyD88-interacting partners, FLAP-1 was
      found to be an activator of NF-kappaB, the key transcription factor in immune
      response. This integrated approach provides global information on the functional
      link between MyD88 and other proteins in transducing the TLR-mediated signal and
      is generally applicable to in vivo analyses of other signaling pathways.

PMID- 15952742
TI  - Tagging-via-substrate strategy for probing O-GlcNAc modified proteins.
AB  - Identification of proteins bearing a specific post-translational modification
      would imply functions of the modification. Proteomic analysis of post
      translationally modified proteins is usually challenging due to high complexity
      and wide dynamic range, as well as unavailability of efficient methods to enrich
      the proteins of interest. Here, we report a strategy for the detection,
      isolation, and profiling of O-linked N-acetylglucosamine (O-GlcNAc) modified
      proteins, which involves three steps: metabolic labeling of cells with an
      unnatural GlcNAc analogue, peracetylated azido-GlcNAc; chemoselective conjugation
      of azido-GlcNAc modified proteins via the Staudinger ligation, which is specific
      between phosphine and azide, using a biotinylated phosphine capture reagent; and
      detection and affinity purification of the resulting conjugated O-GlcNAc modified
      proteins. Since the approach relies on a tag (azide) in the substrate, we
      designated it the tagging-via-substrate (TAS) strategy. A similar strategy was
      used previously for protein farnesylation, phosphorylation, and sumoylation.
      Using this approach, we were able to specifically label and subsequently detect
      azido-GlcNAc modified proteins from the cytosolic lysates of HeLa, 3T3, COS-1,
      and S2 cell lines, suggesting the azido-substrate could be tolerated by the
      enzymatic systems among these cells from diverse biological species. We isolated
      azido-GlcNAc modified proteins from the cytosolic extract of S2 cells and
      identified 10 previously reported and 41 putative O-GlcNAc modified proteins, by
      nano-HPLC-MS/MS. Our study demonstrates that the TAS approach is a useful tool
      for the detection and proteomic analysis of O-GlcNAc modified proteins.

PMID- 15952744
TI  - Predicting enzyme subclass by functional domain composition and pseudo amino acid
      composition.
AB  - As a continuous effort to use the sequence approach to identify enzymatic
      function at a deeper level, investigations are extended from the main enzyme
      classes (Protein Sci. 2004, 13, 2857-2863) to their subclasses. This is
      indispensable if we wish to understand the molecular mechanism of an enzyme at a
      deeper level. For each of the 6 main enzyme classes (i.e., oxidoreductase,
      transferase, hydrolase, lyase, isomerase, and ligase), a subclass training
      dataset is constructed. To reduce homologous bias, a stringent cutoff was imposed
      that all the entries included in the datasets have less than 40% sequence
      identity to each other. To catch the core feature that is intimately related to
      the biological function, the sample of a protein is represented by hybridizing
      the functional domain composition and pseudo amino acid composition. On the basis
      of such a hybridization representation, the FunD-PseAA predictor is established.
      It is demonstrated by the jackknife cross-validation tests that the overall
      success rate in identifying the 21 subclasses of oxidoreductases is above 86%,
      and the corresponding rates in identifying the subclasses of the other 5 main
      enzyme classes are 94-97%. The high success rates imply that the FunD-PseAA
      predictor may become a useful tool in bioinformatics and proteomics of the post
      genomic era.

PMID- 15952743
TI  - Mass spectrometric analysis of the Schistosoma mansoni tegumental sub-proteome.
AB  - Schistosoma mansoni is a parasitic worm that lives in the blood vessels of its
      host. We mapped the S. mansoni tegumental outer-surface structure proteome by 1D
      SDS-PAGE and LC-MS/MS and an EST-database from the ongoing genome-sequencing
      project. We identified 740 proteins of which 43 were tegument-specific. Many of
      these proteins show no homology to any nonschistosomal protein, demonstrating
      that the schistosomal outer-surface comprises specific and unique proteins,
      likely to be critical for parasite survival.

PMID- 15952745
TI  - Direct tandem mass spectrometry reveals limitations in protein profiling
      experiments for plasma biomarker discovery.
AB  - The low molecular weight plasma proteome and its biological relevance are not
      well defined; therefore, experiments were conducted to directly sequence and
      identify peptides observed in plasma and serum protein profiles. Protein
      fractionation, matrix-assisted laser desorption ionization mass spectrometry
      (MALDI-MS) profiling, and liquid-chromatography coupled to MALDI tandem mass
      spectrometry (MS/MS) sequencing were used to analyze the low molecular weight
      proteome of heparinized plasma. Four fractionation techniques using functionally
      derivatized 96-well plates were used to extract peptides from plasma. Tandem TOF
      was successful for identifying peptides up to m/z 5500 with no prior knowledge of
      the sequence and was also used to verify the sequence assignments for larger ion
      signals. The peptides (n>250) sequenced in these profiles came from a
      surprisingly small number of proteins (n approximately 20), which were all common
      to plasma, including fibrinogen, complement components, antiproteases, and
      carrier proteins. The cleavage patterns were consistent with those of known
      plasma proteases, including initial cleavages by thrombin, plasmin and complement
      proteins, followed by aminopeptidase and carboxypeptidase activity. On the basis
      of these data, we discuss limitations in biomarker discovery in the low molecular
      weight plasma or serum proteome using crude fractionation coupled to MALDI-MS
      profiling.

PMID- 15952746
TI  - Postfractionation for enhanced proteomic analyses: routine electrophoretic
      methods increase the resolution of standard 2D-PAGE.
AB  - Here we have addressed common issues of resolution in two-dimensional
      polyacrylamide gel electrophoresis (2DE) experiments including proteins 'stacked'
      at pH extremes, unresolved peptides migrating at the front of separation, and
      areas of the 2D gel obscured by high abundance proteins. Postfractionation, by
      selective application of well-established electrophoretic separations immediately
      following standard 2DE, yields markedly improved resolution in these traditional
      problem areas using no more specialized equipment or techniques than SDS-PAGE
      itself.

PMID- 15952747
TI  - Improved protein identification through the use of unstained gels.
AB  - In this work, a method for improved protein identification of low-abundance
      proteins using unstained gels, in combination with robotics and matrix-assisted
      laser desorption/ionization tandem mass spectrometry, has been developed and
      evaluated. Omitting the silver-staining process resulted in increased protein
      identification scores, an increase in the number of peptides observed in the
      MALDI mass spectrum, and improved quality of the tandem mass spectrometry data.

PMID- 15952748
TI  - Integrated approach for manual evaluation of peptides identified by searching
      protein sequence databases with tandem mass spectra.
AB  - Quantitative proteomics relies on accurate protein identification, which often is
      carried out by automated searching of a sequence database with tandem mass
      spectra of peptides. When these spectra contain limited information, automated
      searches may lead to incorrect peptide identifications. It is therefore necessary
      to validate the identifications by careful manual inspection of the mass spectra.
      Not only is this task time-consuming, but the reliability of the validation
      varies with the experience of the analyst. Here, we report a systematic approach
      to evaluating peptide identifications made by automated search algorithms. The
      method is based on the principle that the candidate peptide sequence should
      adequately explain the observed fragment ions. Also, the mass errors of
      neighboring fragments should be similar. To evaluate our method, we studied
      tandem mass spectra obtained from tryptic digests of E. coli and HeLa cells.
      Candidate peptides were identified with the automated search engine Mascot and
      subjected to the manual validation method. The method found correct peptide
      identifications that were given low Mascot scores (e.g., 20-25) and incorrect
      peptide identifications that were given high Mascot scores (e.g., 40-50). The
      method comprehensively detected false results from searches designed to produce
      incorrect identifications. Comparison of the tandem mass spectra of synthetic
      candidate peptides to the spectra obtained from the complex peptide mixtures
      confirmed the accuracy of the evaluation method. Thus, the evaluation approach
      described here could help boost the accuracy of protein identification, increase
      number of peptides identified, and provide a step toward developing a more
      accurate next-generation algorithm for protein identification.

PMID- 15952749
TI  - Peptide identification using vectors of small fragment ions.
AB  - Traditionally, peptide identification using fragmentation spectra relies on
      extracting the maximum amount of information from spectra. Using different
      combinations of small ion masses, we show that identifying a small number of
      fragment ions in a spectrum is sufficient for peptide identification. We consider
      y2-, y3-, b2-, and b3-ions and find the combination of b2-y2 to be sufficient for
      many peptides. Adding either the y3- or the b3-ion increases specificity and
      allows reliable peptide identification in the human proteome. Fragmentation
      spectra and peptides are represented as n-dimensional vectors, where n is given
      by the number of fragment ions considered, and the peptide mass. The
      identification score is given by the Euclidian distance between the spectra and
      the matching peptide in n-dimensional space. We show that this approach, using
      minimal information, allows for precise and fast peptide identification.

PMID- 15952751
TI  - Identification of proteins expressing differences among isolates of Meloidogyne
      spp. (Nematoda: Meloidogynidae) by nano-liquid chromatography coupled to ion-trap
      mass spectrometry.
AB  - Total protein variation (up to ninety-five different positions) was revealed by
      two-dimensional electrophoresis (2-DE) in 18 isolates from populations of M.
      arenaria (6 isolates), M. incognita (10), M. javanica (1) plus an unclassified
      isolate in a previously reported study. Isolates of M. arenaria, M. javanica,
      Meloidogyne sp., and M. incognita formed two separate groups defined on the basis
      of two sets of protein positions that could be considered as diagnostic
      characters, but we could not identify these proteins by MALDI-TOF. To identify
      these marker positions, nano-liquid chromatography as peptides separation method
      was coupled to an ion-trap mass spectrometer for induced real-time fragmentation
      of eluted peptides. Group diagnostic proteins for M. incognita and M. arenaria
      were in-gel digested and on line analyzed by tandem mass spectrometry (LC-MS/MS).
      Six proteins out of seven selected spots were unambiguously identified by the
      analysis of the corresponding MS/MS (MS2) spectrum from parent ions
      fragmentation: Actin, Enolase, CG3752-PA protein similar to Aldehyde
      Dehydrogenase, HSP-60 and Translation initiation factor elF-4A. In M. incognita
      sample, de novo sequencing experiment of doubly charged ion at m/z=936.9 Da in
      spot 29 identified as enolase, reveals three residue substitutions (K to T, N to
      T, and D to E) when tentative sequence was compared with that of Anisakis simplex
      and Onchocerca volvulus enolase, thus three SNPs (single nucleotide
      polymorphisms) were also possibly identified.

PMID- 15952750
TI  - Replaceable cross-linked polyacrylamide for high performance separation of
      proteins.
AB  - An alternative sieving matrix, replaceable cross-linked polyacrylamide (rCPA),
      was developed for sodium dodecyl sulfate capillary gel electrophoresis (SDS-CGE)
      separation of proteins. This rCPA could be conveniently pressurized into
      separation capillaries under a pressure of 80 psi. SDS-CGE separations using this
      matrix generated high resolutions for a wide range (approximately 4 kD to
      approximately 300 kD) of proteins. When compared to the most frequently used
      sieving matrixes, the rCPA permitted the highest resolutions with comparable or
      increased separation speed for protein separations.

PMID- 15952752
TI  - Primordial proteins and HIV-Part II.
AB  - Nanobacteria are suspected to be responsible for a number of diseases, i.e.,
      kidney stones, heart disease, ovarian cancer, peripheral neuropathy, and reduced
      bone mineral density. Being protected by a mineral shell consisting of apatite,
      the nanovesicles can enter eukaryotic cells. Depending on the host's stress
      level, nanobacteria may carry a substantial layer of a protein based slime,
      instrumental in collecting calcium phosphate from the environment. Calcium
      phosphate is known to mediate the uptake of nucleic acids by eukaryotic cells.
      Surprisingly, a pathogenic effect of nanobacteria in HIV can be derived primarily
      from the trafficking of calcium phosphate in HIV infected cells, performed by
      primordial proteins. The inescapable conclusion is that nanobacteria could
      promote genetic diversity in HIV.

PMID- 15952753
TI  - Geochemical and cosmochemical materials.

PMID- 15952754
TI  - Trends in environmental analysis.

PMID- 15952755
TI  - Pharmaceuticals and related drugs.

PMID- 15952757
TI  - Process analytical chemistry.

PMID- 15952756
TI  - Proteomics: from gel based to gel free.

PMID- 15952758
TI  - Water analysis: emerging contaminants and current issues.

PMID- 15952759
TI  - Forensic science.

PMID- 15952760
TI  - Recent advances in our understanding of atmospheric chemistry and climate made
      possible by on-line aerosol analysis instrumentation.

PMID- 15952761
TI  - Advances in polymerase chain reaction on microfluidic chips.

PMID- 15952762
TI  - Ligand-protein interaction in biomembrane carriers. The induced transition fit of
      transport catalysis.
AB  - Carrier-linked transport through biomembranes is treated under the view of
      catalysis. As in enzymes, substrate-protein interaction yields catalytic energy
      in overcoming the activation barrier. At variance with enzymes, catalytic energy
      is concentrated on structural changes of the carrier rather than on the substrate
      destabilization for facilitating the global protein rearrangements during
      transport. A transition state is invoked in which the binding site assumes the
      best fit to the substrate, whereas in the two ground (internal and external)
      states, the fit is poor. The maximum binding energy released in the transition
      state provides catalytic energy to enable the large carrier protein
      transformations associated with transport. This "induced transition fit" (ITF) of
      carrier catalysis provides a framework of rules, concerning specificity,
      unidirectional versus exchange type transport, directing inhibitors to the ground
      state instead of the transition state, and excluding simultaneous chemical and
      transport catalysis (vectorial group translocation). The possible role of
      external energy sources (ATP and Deltapsi) in supplementing the catalytic energy
      is elucidated. The analysis of the structure-function relationship based on new
      carrier structures may be challenged to account for the workings of the ITF.

PMID- 15952763
TI  - Evidence from biosynthetically incorporated strontium and FTIR difference
      spectroscopy that the C-terminus of the D1 polypeptide of photosystem II does not
      ligate calcium.
AB  - Recent FTIR studies have provided evidence that the C-terminal alpha-COO(-) group
      of the D1 polypeptide at D1-Ala344 is a unidentate ligand of a Mn ion in
      photosystem II [Chu, H.-A., Hiller, W., and Debus, R. J. (2004) Biochemistry 43,
      3152-3166; Kimura, Y., Mizusawa, N., Yamanari, T., Ishii, A., and Ono, T.-A.
      (2005) J. Biol. Chem. 280, 2078-2083]. However, the FTIR data could not exclude
      Ca ligation. Furthermore, the recent approximately 3.5 A X-ray crystallographic
      structural model positions the alpha-COO(-) group of D1-Ala344 near a Ca ion
      [Ferreira, K. N., Iverson, T. M., Maghlaoui, K., Barber, J., and Iwata, S. (2004)
      Science 303, 1831-1838]. Therefore, to conclusively establish whether the alpha
      COO(-) group of D1-Ala344 ligates Mn or Ca, the symmetric carboxylate stretching
      mode of the alpha-COO(-) group of D1-Ala344 was identified in the S(2)-minus-S(1)
      FTIR difference spectrum of PSII particles having Sr substituted for Ca. Cells of
      the cyanobacterium Synechocystis sp. PCC 6803 were propagated in media having Sr
      substituted for Ca and containing either l-[1-(13)C]alanine or unlabeled ((12)C)
      alanine. The S(2)-minus-S(1) FTIR difference spectra of the purified PSII
      particles show that substituting Sr for Ca alters several carboxylate stretching
      modes, including some that may correspond to one or more metal ligands, but
      importantly does not alter the symmetric carboxylate stretching mode of the alpha
      COO(-) group of D1-Ala344. In unlabeled PSII particles, this mode appears at
      approximately 1356 cm(-)(1) in the S(1) state and at either approximately 1337 or
      approximately 1320 cm(-)(1) in the S(2) state, irrespective of whether the PSII
      particles contain Ca or Sr. These data are inconsistent with Ca ligation and
      show, therefore, that the C-terminal alpha-COO(-) group of the D1 polypeptide
      ligates a Mn ion. These data also show that substituting Ca with the larger Sr
      ion perturbs other unidentified carboxylate groups, at least one of which may
      ligate the Mn(4) cluster.

PMID- 15952764
TI  - Inhibitors of metallo-beta-lactamase generated from beta-lactam antibiotics.
AB  - The resistance of bacteria to the normally lethal action of beta-lactam
      antibiotics is largely due to the production of beta-lactamases that catalyze the
      hydrolysis of the beta-lactam. One class of these enzymes is a zinc-dependent
      metallo-beta-lactamase for which there are no clinically available inhibitors.
      The hydrolysis of cephalosporin beta-lactam antibiotics generates
      dihydrothiazines which subsequently undergo isomerization at C6 by C-S bond
      cleavage and through the intermediacy of a thiol. These thiols can be trapped by
      the beta-lactamase from Bacillus cereus, causing inhibition of the enzyme. The
      rate of production of the thiol corresponds to the rate of inhibition, and the
      inhibition constants are in the micromolar range but vary with the nature of the
      cephalosporin derivative. NMR studies have identified the structure of the thiols
      causing inhibition and also show that the thiol binds to the zinc ion, which in
      turn perturbs the metal-bound histidines. Inhibition is slowly removed as the
      thiol becomes oxidized or undergoes further degradation. The thiol intermediate
      generated from cephalothin is a slow binding inhibitor. There is no observed
      inhibition from the analogous degradation products from penicillins.

PMID- 15952765
TI  - Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8
      dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84
      and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic
      studies.
AB  - Deletion mutagenesis, biochemical, and X-ray crystallographic studies have shown
      that loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase (HPPK) is required for the assembly of the active center, plays
      an important role in the stabilization of the ternary complex of HPPK with MgATP
      and 6-hydroxymethyl-7,8-dihydropterin (HP), and is essential for catalysis.
      Whether the critical functional importance of loop 3 is due to the interactions
      between residues R84 and W89 and the two substrates has been addressed by site
      directed mutagenesis, biochemical, and X-ray crystallographic studies.
      Substitution of R84 with alanine causes little changes in the dissociation
      constants and kinetic constants of the HPPK-catalyzed reaction, indicating that
      R84 is not important for either substrate binding or catalysis. Substitution of
      W89 with alanine increases the K(d) for the binding of MgATP by a factor of 3,
      whereas the K(d) for HP increases by a factor of 6, which is due to the increase
      in the dissociation rate constant. The W89A mutation decreases the rate constant
      for the chemical step of the forward reaction by a factor of 15 and the rate
      constant for the chemical step of the reverse reaction by a factor of 25. The
      biochemical results of the W89A mutation indicate that W89 contributes somewhat
      to the binding of HP and more significantly to the chemical step. The crystal
      structures of W89A show that W89A has different conformations in loops 2 and 3,
      but the critical catalytic residues are positioned for catalysis. When these
      results are taken together, they suggest that the critical functional importance
      of loop 3 is not due to the interactions of the R84 guanidinium group or the W89
      indole ring with the substrates.

PMID- 15952766
TI  - A mass spectrometric determination of the conformation of dimeric apolipoprotein
      A-I in discoidal high density lipoproteins.
AB  - Discoidal forms of high density lipoproteins (HDL) are critical intermediates
      between lipid-poor apolipoprotein A-I (apo A-I), the major protein constituent of
      HDL, and the mature spherical forms that comprise the bulk of circulating
      particles. Thus, many studies have focused on understanding apoA-I structure in
      discs reconstituted in vitro. Recent theoretical and experimental work supports a
      "belt" model for apoA-I in which repeating amphipathic helical domains run
      parallel to the plane of the lipid disc. However, disc-associated apoA-I can
      adopt several tertiary arrangements that are consistent with a belt orientation.
      To distinguish among these, we cross-linked near-neighbor Lys groups in
      homogeneous 96 A discs containing exactly two molecules of apoA-I. After
      delipidation and tryptic digestion, mass spectrometry was used to identify 9
      intermolecular and 11 intramolecular cross-links. The cross-linking pattern
      strongly suggests a "double-belt" molecular arrangement for apoA-I in which two
      apoA-I molecules wrap around the lipid bilayer disc forming two stacked rings in
      an antiparallel orientation with helix 5 of each apoA-I in juxtaposition (LL5/5
      orientation). The data also suggests the presence of an additional double-belt
      orientation with a shifted helical registry (LL5/2 orientation). Furthermore, a
      78 A particle with two molecules of apoA-I fit a similar double-belt motif with
      evidence for conformational changes in the N-terminus and the region near helix
      5. A comparison of this work to a previous study is suggestive that a third
      molecule of apoA-I can form a hairpin in larger particles containing three
      molecules of apoA-I.

PMID- 15952767
TI  - Communication between the two active sites of glutathione S-transferase A1-1,
      probed using wild-type-mutant heterodimers.
AB  - To study the communication between the two active sites of dimeric glutathione S
      transferase A1-1, we used heterodimers containing one wild-type (WT) active site
      and one active site with a single mutation at either Tyr9, Arg15, or Arg131. Tyr9
      and Arg15 are part of the active site of the same subunit, while Arg131
      contributes to the active site of the opposite subunit. The V(max) values of Tyr9
      and Arg15 mutant enzymes were less than 2% that of WT, indicating their
      importance in catalysis. In contrast, V(max) values of Arg131 mutant enzymes were
      about 50-90% of that of WT enzyme while K(m)(GSH) values were approximately 3-8
      times that of WT, suggesting that Arg131 plays a role in glutathione binding. The
      mutant enzyme (with a His(6) tag) and the WT enzyme (without a His(6) tag) were
      used to construct heterodimers (WT-Y9F, WT-Y9T, WT-R15Q, WT-R131M, WT-R131Q, and
      WT-R131E) by incubation of a mixture of wild-type and mutant enzyme at pH 7.5 in
      buffer containing 1,6-hexanediol, followed by dialysis against buffer lacking the
      organic solvent. The resultant heterodimers were separated from the wild-type and
      mutant homodimers using chromatography on nickel-nitrilotriacetic acid agarose.
      The V(max) values of all heterodimers were lower than expected for independent
      active sites. Our experiments demonstrate that mutation of an amino acid residue
      in one active site affects the activity in the other active site. Modeling
      studies show that key amino acid residues and water molecules connect the two
      active sites. This connectivity is responsible for the cross-talk between the
      active sites.

PMID- 15952768
TI  - Structure of the O-acetylserine sulfhydrylase isoenzyme CysM from Escherichia
      coli.
AB  - The enzyme O-acetylserine sulfhydrylase participates in the biosynthesis of l
      cysteine in bacteria and plants. The structure of isoenzyme B (CysM) from
      Escherichia coli was established in a hexagonal crystal form at 2.7 A resolution
      (wild-type) and in a merohedrally twinned tetragonal crystal form at 2.1 A
      resolution (surface mutant). Structural superpositions revealed the variations
      with respect to isoenzyme A (CysK) and explained the different substrate
      specificities. A geometric model of the reaction catalyzed by CysM is proposed.
      Both isoenzymes are used for the production of l-amino acid derivatives as
      building blocks for the synthesis of peptides and peptidomimetic drugs. Since the
      structure of CysM revealed a remarkable main chain variation at the active
      center, it constitutes a further starting point for engineering mutants with
      novel substrate specificities.

PMID- 15952769
TI  - Pulsed hydrogen exchange and electrospray charge-state distribution as
      complementary probes of protein structure in kinetic experiments: implications
      for ubiquitin folding.
AB  - The possible involvement of "hidden" kinetic intermediates in the apparent two
      state folding of some proteins is currently a matter of debate. This study uses
      time-resolved electrospray ionization (ESI) mass spectrometry with on-line pulsed
      hydrogen-deuterium exchange (HDX) for monitoring the refolding of acid/methanol
      denatured ubiquitin. It is demonstrated that the ESI charge-state distribution
      (CSD) and the extent of HDX represent nonredundant probes of the protein
      structure in solution. When considered in isolation, the data provided by both of
      these probes are consistent with a two-state behavior, involving only denatured
      ubiquitin D and refolded protein F. However, a careful comparison of the CSD and
      HDX kinetics reveals the presence of an additional species, exhibiting a CSD like
      the folded protein but showing non-native HDX characteristics. This kinetic
      intermediate, D*, is in rapid equilibrium with D, such that the overall reaction
      is consistent with the mechanism D <--> D* --> F. The results of this work
      suggest that the occurrence of transient intermediates may be more widespread
      than commonly thought, especially in cases where a cursory analysis indicates two
      state behavior.

PMID- 15952770
TI  - Structural basis for the retroreduction of inactivated peroxiredoxins by human
      sulfiredoxin.
AB  - Sufiredoxins (Srx) repair the inactivated forms of typical two-Cys peroxiredoxins
      (Prx) implicated in hydrogen peroxide-mediated cell signaling. The reduction of
      the cysteine sulfinic acid moiety within the active site of the Prx by Srx
      involves novel sulfur chemistry and the use of ATP and Mg(2+). The 1.65 A crystal
      structure of human Srx (hSrx) exhibits a new protein fold and a unique nucleotide
      binding motif containing the Gly98-Cys99-His100-Arg101 sequence at the N-terminus
      of an alpha-helix. HPLC analysis of the reaction products has confirmed that the
      site of ATP cleavage is between the beta- and gamma-phosphate groups. Cys99 and
      the gamma-phosphate of ATP, modeled within the active site of the 2.0 A ADP
      product complex structure, are adjacent to large surface depressions containing
      additional conserved residues. These features and the necessity for significant
      remodeling of the Prx structure suggest that the interactions between hSrx and
      typical two-Cys Prxs are specific. Moreover, the concave shape of the hSrx active
      site surface appears to be ideally suited to interacting with the convex surface
      of the toroidal Prx decamer.

PMID- 15952771
TI  - Identification of the molecular mechanisms by which the diterpenoid salvinorin A
      binds to kappa-opioid receptors.
AB  - Salvinorin A is a naturally occurring hallucinogenic diterpenoid from the plant
      Salvia divinorumthat selectively and potently activates kappa-opioid receptors
      (KORs). Salvinorin A is unique in that it is the only known lipid-like molecule
      that selectively and potently activates a G-protein coupled receptor (GPCR),
      which has as its endogenous agonist a peptide; salvinorin A is also the only
      known non-nitrogenous opioid receptor agonist. In this paper, we identify key
      residues in KORs responsible for the high binding affinity and agonist efficacy
      of salvinorin A. Surprisingly, we discovered that salvinorin A was stabilized in
      the binding pocket by interactions with tyrosine residues in helix 7 (Tyr313 and
      Tyr320) and helix 2 (Tyr119). Intriguingly, activation of KORs by salvinorin A
      required interactions with the helix 7 tyrosines Tyr312, Tyr313, and Tyr320 and
      with Tyr139 in helix 3. In contrast, the prototypical nitrogenous KOR agonist
      U69593 and the endogenous peptidergic agonist dynorphin A (1-13) showed
      differential requirements for these three residues for binding and activation. We
      also employed a novel approach, whereby we examined the effects of cysteine
      substitution mutagenesis on the binding of salvinorin A and an analogue with a
      free sulfhydryl group, 2-thiosalvinorin B. We discovered that residues predicted
      to be in close proximity, especially Tyr313, to the free thiol of 2
      thiosalvinorin B when mutated to Cys showed enhanced affinity for 2
      thiosalvinorin B. When these findings are taken together, they imply that the
      diterpenoid salvinorin A utilizes unique residues within a commonly shared
      binding pocket to selectively activate KORs.

PMID- 15952772
TI  - Identification of a Cd2+- and Zn2+-binding site in cytochrome c using FTIR
      coupled to an ATR microdialysis setup and NMR spectroscopy.
AB  - Fourier transform infrared (FTIR) difference spectroscopy allows the study of
      molecular changes occurring at active sites in proteins with high sensitivity.
      Reactions are triggered by light, potential, or temperature steps and more
      recently by the diffusion of buffers containing effectors above membrane proteins
      deposited as films on ATR crystals. We have adapted a microdialysis system to an
      ATR, to study metal sites in soluble proteins. In this study, we identified a
      Cd(2+)- or Zn(2+)-binding site in cytochrome c with dissociation constants of 17
      and 42 microM, respectively, which affects the oxidation rate of ferrocytochrome
      c by hydrogen peroxide. Using the microdialysis ATR-FTIR setup, we determined
      that a histidine and the carboxylate group of a glutamate are involved in Zn(2+)
      binding. The implication of His 33 and Glu 104 in the binding site was deduced
      from the comparison of FTIR data recorded with horse heart and the variant tuna
      cytochrome c lacking these two amino acids. A two-dimensional NMR analysis of the
      Zn(2+)-binding site in horse heart cytochrome c confirmed that His 33 and
      residues close to the C terminus are sensitive to Zn(2+) binding. This study
      demonstrates that the microdialysis ATR-FTIR setup is promising for the analysis
      of metal sites in proteins. From H(2)O/(2)H(2)O exchange experiments, we
      concluded that the impact of Zn(2+) and Cd(2+) binding on the oxidation kinetics
      of ferrocytochrome c by H(2)O(2) is associated to the perturbation of a hydrogen
      bonding network involving His 33 that is sensitive to the redox state of
      cytochrome c.

PMID- 15952773
TI  - Accessibility of the distal heme face, rather than Fe-His bond strength,
      determines the heme-nitrosyl coordination number of cytochromes c': evidence from
      spectroscopic studies.
AB  - The heme coordination chemistry and spectroscopic properties of Rhodobacter
      capsulatus cytochrome c' (RCCP) have been compared to data from Alcaligenes
      xylosoxidans (AXCP), with the aim of understanding the basis for their different
      reactivities with nitric oxide (NO). Whereas ferrous AXCP reacts with NO to form
      a predominantly five-coordinate heme-nitrosyl complex via a six-coordinate
      intermediate, RCCP forms an equilibrium mixture of six-coordinate and five
      coordinate heme-nitrosyl species in approximately equal proportions. Ferrous RCCP
      and AXCP both exhibit high Fe-His stretching frequencies (227 and 231 cm(-)(1),
      respectively), suggesting that factors other than the Fe-His bond strength
      account for their differences in heme-nitrosyl coordination number. Resonance
      Raman spectra of ferrous-nitrosyl RCCP confirm the presence of both five
      coordinate and six-coordinate heme-NO complexes. The six-coordinate heme-nitrosyl
      of RCCP exhibits a fairly typical Fe-NO stretching frequency (569 cm(-)(1)), in
      contrast to the relatively high value (579 cm(-)(1)) of the AXCP six-coordinate
      heme-nitrosyl intermediate. It is proposed that NO experiences greater steric
      hindrance in binding to the distal face of AXCP, as compared to RCCP, leading to
      a more distorted Fe-N-O geometry and an elevated Fe-NO stretching frequency.
      Evidence that RCCP has a more accessible distal coordination site than in AXCP
      stems from the fact that ferric RCCP readily forms a heme complex with exogenous
      imidazole, whereas AXCP does not. A model is proposed in which distal heme-face
      accessibility, rather than the proximal Fe-His bond strength, determines the heme
      nitrosyl coordination number in cytochromes c'.

PMID- 15952774
TI  - A zinc(II)/lead(II)/cadmium(II)-inducible operon from the Cyanobacterium anabaena
      is regulated by AztR, an alpha3N ArsR/SmtB metalloregulator.
AB  - A novel Zn(II)/Pb(II)/Cd(II)-responsive operon that consists of genes encoding a
      Zn(II)/Pb(II) CPx-ATPase efflux pump (aztA) and a Zn(II)/Cd(II)/Pb(II)-specific
      SmtB/ArsR family repressor (aztR) has been identified and characterized from the
      cyanobacterium Anabaena PCC 7120. In vivo real time quantitative RT-PCR assays
      reveal that both aztR and aztA expression are induced by divalent metal ions
      Zn(II), Cd(II), and Pb(II) but not by other divalent [Co(II), Ni(II)] or
      monovalent metal ions [Cu(I) and Ag(I)]. The introduction of a plasmid containing
      the azt operon into a Zn(II)/Cd(II)-hypersensitive Escherichia coli strain GG48
      functionally restores Zn(II) and Pb(II) resistance with a limited effect on
      Cd(II) resistance. Gel mobility shift assays and aztR O/P-lacZ induction
      experiments confirm that AztR is the metal-regulated repressor of this operon. In
      vitro biochemical and mutagenesis studies indicate that AztR contains a sole
      metal-binding site, designated the alpha3N site, that binds Zn(II), Cd(II), and
      Pb(II) with a high affinity. Optical absorption spectra of Co(II)- and Cd(II)
      substituted AztR and (113)Cd NMR spectroscopy of (113)Cd(II)-substituted AztR
      reveal that the sole alpha3N site in AztR is a CadC-like distorted tetrahedral
      S(3)(N,O) metal site. The first metal-coordination shell in the AztR alpha3N site
      differs from other alpha3N family members that sense Cd(II)/Pb(II) and those
      alpha5 repressors that sense Zn(II)/Co(II). Our results reveal that the alpha3N
      site in AztR mediates derepression of the azt operon in the presence of Zn(II),
      as well as Cd(II) and Pb(II); this might have provided Anabaena with an
      evolutionary advantage to adapt to heavy-metal-rich environments, while
      maintaining homeostasis of an essential metal ion, Zn(II).

PMID- 15952775
TI  - HAD superfamily phosphotransferase substrate diversification: structure and
      function analysis of HAD subclass IIB sugar phosphatase BT4131.
AB  - The BT4131 gene from the bacterium Bacteroides thetaiotaomicron VPI-5482 has been
      cloned and overexpressed in Escherichia coli. The protein, a member of the
      haloalkanoate dehalogenase superfamily (subfamily IIB), was purified to
      homogeneity, and its X-ray crystal structure was determined to1.9 A resolution
      using the molecular replacement phasing method. BT4131 was shown by an extensive
      substrate screen to be a broad-range sugar phosphate phosphatase. On the basis of
      substrate specificity and gene context, the physiological function of BT4131 in
      chitin metabolism has been tentatively assigned. Comparison of the BT4131
      structure alpha/beta cap domain structure with those of other type IIB enzymes
      (phosphoglycolate phosphatase, trehalose-6-phosphate phosphatase, and proteins of
      unknown function known as PDB entries , , and ) identified two conserved loops
      (BT4131 residues 172-182 and 118-130) in the
      alphabetabeta(alphabetaalphabeta)alphabetabeta type caps and one conserved loop
      in the alphabetabetaalphabetabeta type caps, which contribute residues for
      contact with the substrate leaving group. In BT4131, the two loops contribute one
      polar and two nonpolar residues to encase the displaced sugar. This finding is
      consistent with the lax specificity BT4131 has for the ring size and
      stereochemistry of the sugar phosphate. In contrast, substrate docking showed
      that the high-specificity phosphoglycolate phosphatase (PDB entry ) uses a single
      substrate specificity loop to position three polar residues for interaction with
      the glycolate leaving group. We show how active site "solvent cages" derived from
      analysis of the structures of the type IIB HAD phosphatases could be used in
      conjunction with the identity of the residues stationed along the cap domain
      substrate specificity loops, as a means of substrate identification.

PMID- 15952776
TI  - Kinetic control of thiamin diphosphate activation in enzymes studied by proton
      nitrogen correlated NMR spectroscopy.
AB  - Proton-nitrogen correlated NMR studies were performed on thiamin diphosphate,
      which has been specifically labeled with (15)N at the 4'-amino group. After
      reconstitution of the labeled coenzyme with the apoenzymes of both wild-type
      pyruvate decarboxylase from Zymomonas mobilis and the E50Q variant, a high-field
      shift of the (15)N signal of approximately 4 ppm is observed at pH 5.9 when
      compared to that of the free coenzyme, indicating a higher electron density at
      the 4'-amino nitrogen in the enzyme-bound state. The pH dependence of the
      chemical shift of the (15)N signals in the (1)H-(15)N heteronuclear single
      quantum coherence NMR spectra reveals typical titration curves for the free as
      well as the reconstituted coenzyme with nearly identical chemical shift end
      points. The midpoints of the transitions are at pH 5.3 and 5.0 for the free and
      enzyme-bound coenzyme, respectively. We conclude that the tremendous rate
      acceleration of C2-H deprotonation in ThDP enzymes is mainly the result of the
      enforced V conformation of the cofactor in the active site being perfectly suited
      to allowing intramolecular acid-base catalysis.

PMID- 15952777
TI  - Green fluorescent protein variants as ratiometric dual emission pH sensors. 3.
      Temperature dependence of proton transfer.
AB  - In parts 1 and 2 of this series [Hanson, G. T., McAnaney, T. B., Park, E. S.,
      Rendell, M. E. P., Yarbrough, D. K., Chu, S. Y., Xi, L. X., Boxer, S. G.,
      Montrose, M. H., and Remington, S. J. (2002) Biochemistry 41, 15477-15488;
      McAnaney, T. B., Park, E. S., Hanson, G. T., Remington, S. J., and Boxer, S. G.
      (2002) Biochemistry 41, 15489-15494], we described the structure, excited-state
      dynamics, and applications of pH-sensitive, ratiometric dual emission green
      fluorescent protein (deGFP) variants with fluorescence emission that is modulated
      between blue (lambda(max) approximately equal 465 nm) and green (lambda(max)
      approximately equal 515 nm) depending on the pH of the bulk solvent. In this
      paper, we consider the energetic origin of the dual emission properties of these
      GFP variants by examining the temperature dependence of the steady-state
      absorption and fluorescence emission. In most cases, the quantum yield of the
      green emission decreased as the temperature was lowered, indicating that the
      excited-state proton transfer (ESPT) which produces the green emitting form is an
      activated process. The activation energies of ESPT, determined by modeling the
      quantum yields of both blue and green emissions between 260 and 298 K in the
      context of a simple photocycle, were found to be larger at low pH than at high
      pH. These results indicate that the ratiometric dual emission properties of deGFP
      mutants are due to this pH-sensitive ESPT rate, combined with a modulation of the
      ground-state neutral and anionic chromophore populations with pH. The time
      resolved fluorescence of one of the deGFP mutants was studied in detail. The time
      resolved emission spectra of this mutant are the first ultrafast spectra obtained
      for a GFP. These spectra demonstrate that the rising kinetics for green emission,
      considered a hallmark of ESPT, is the sum of the contribution from both the
      neutral and intermediate anionic forms of the chromophore at the probe wavelength
      and may not be observed in all mutants that undergo ESPT, depending on the
      relative contributions of the two forms.

PMID- 15952778
TI  - Copper reduction by the octapeptide repeat region of prion protein: pH dependence
      and implications in cellular copper uptake.
AB  - The physiological function of the prion protein (PrP) remains enigmatic despite
      its established involvement in the pathogenesis of spongiform encephalopathies.
      PrP is a glycolipid-anchored membrane protein, which constitutively recycles
      between the cell surface and an endosomal compartment. The N-terminal region of
      PrP contains a four tandem repeat (OP4) of the octapeptide PHGGGWGQ (OP) that
      binds and reduces Cu(II) ions. We have examined the kinetic properties of the OP4
      mediated Cu(II) reduction and found that OP4 exhibits the highest reduction
      activity around pH 6.5, close to the pH in early endosomes. All four OP units and
      at least one tryptophan side chain are essential for Cu(II) reduction. The
      reaction is described by an uncompetitive substrate inhibition mechanism
      involving a 1:1 Cu(II)-OP4 active intermediate. Structural analysis by Raman
      spectroscopy has revealed that the Cu(II) ion is coordinated by four histidine
      Ntau atoms in the active intermediate and the feasibility of formation of this
      intermediate correlates with the Cu(II) reduction over a pH range from 5.0 to
      8.2. Molecular mechanics calculations suggest that two tryptophan residues of OP4
      are located near the Cu(II) site, being consistent with the importance of redox
      active tryptophan in the Cu(II) reduction. PrP has been proposed to capture
      Cu(II) ions in the extracellular space and release them in the endosome. The
      results of this study strongly suggest that PrP also plays a role in the
      reduction of captured Cu(II) ions prior to their transfer to Cu(I)-specific
      intracellular copper trafficking proteins.

PMID- 15952779
TI  - Interaction of the adenovirus proteinase with protein cofactors with high
      negative charge densities.
AB  - The interactions of the human adenovirus proteinase (AVP) with polymers with high
      negative charge densities were characterized. AVP utilizes two viral cofactors
      for maximal enzyme activity (k(cat)/K(m)), the 11-amino acid peptide from the C
      terminus of virion precursor protein pVI (pVIc) and the viral DNA. The viral DNA
      stimulates covalent AVP-pVIc complexes (AVP-pVIc) as a polyanion with a high
      negative charge density. Here, the interactions of AVP-pVIc with different
      polymers with high negative charge densities, polymers of glutamic acid (polyE),
      were characterized. The rate of substrate hydrolysis by AVP-pVIc increased with
      increasing concentrations of polyE. At higher concentrations of polyE, the
      increase in the rate of substrate hydrolysis approached saturation. Although
      glutamic acid did not stimulate enzyme activity, glutamic acid and NaCl could
      displace DNA from AVP-pVIc.(DNA) complexes; the K(i) values were 230 and 329 nM,
      respectively. PolyE binds to the DNA binding site on AVP-pVIc as polyE and DNA
      compete for binding to AVP-pVIc. The equilibrium dissociation constant for 1.3
      kDa polyE binding to AVP-pVIc was 56 nM. On average, one molecule of AVP-pVIc
      binds to 12 residues in polyE. Comparison of polyE and 12-mer single-stranded DNA
      interacting with AVP-pVIc revealed the binding constants are similar, as are the
      Michaelis-Menten constants for substrate hydrolysis. The number of ion pairs
      formed upon the binding of 1.3 kDa polyE to AVP-pVIc was 2, and the
      nonelectrostatic change in free energy upon binding was -6.5 kcal. These
      observations may be physiologically relevant as they infer that AVP may bind to
      proteins that have regions of negative charge density. This would restrict
      activation of the enzyme to the locus of the cofactor within the cell.

PMID- 15952780
TI  - Proposed structural mechanism of Escherichia coli cAMP receptor protein cAMP
      dependent proteolytic cleavage protection and selective and nonselective DNA
      binding.
AB  - The Escherichia coli cAMP receptor protein (CRP) displays biphasic
      characteristics in protease and beta-galactosidase induction assays at increasing
      cAMP concentrations in response to ligand binding at the secondary binding site
      located between the primary binding site and the DNA binding domain. Two mutants
      were created to determine the mechanistic reason for the CRP biphasic response by
      inhibiting binding of cAMP to the secondary site via interference with the Arg
      181 interaction with the ligand's phosphate. The S179A/R180D/E181H mutant binds
      two cAMP molecules per dimer, does not exhibit a biphasic response, lacks
      selective DNA binding, and has inhibited nonselective DNA binding. The R180K
      mutant binds four cAMP molecules per dimer, exhibits a biphasic response,
      nonselective DNA binding similar to CRP, but has inhibited selective DNA binding
      characteristics. The results are consistent with a 2 x 2-binding site scheme were
      both primary binding sites must be occupied before the secondary binding sites
      are occupied. A structural mechanism suggesting the secondary sites are formed by
      binding of cAMP to the primary sites is proposed. AMMP-generated molecular models
      suggest that R180 orients E181 to produce selective DNA binding, Arg 169
      interactions are necessary for nonselective DNA binding, and the position of Leu
      57 inhibits chymotrypsin cleavage of Phe 136. DNA binding results suggest that
      CRP may be the unknown transcription factor which binds to the temperature
      sensitive dsrA promoter.

PMID- 15952781
TI  - Structure-function relationships of the intact aIF2alpha subunit from the
      archaeon Pyrococcus abyssi.
AB  - Eukaryotic and archaeal initiation factor 2 (e- and aIF2, respectively) are
      heterotrimeric proteins (alphabetagamma) supplying the small subunit of the
      ribosome with methionylated initiator tRNA. The gamma subunit forms the core of
      the heterotrimer. It resembles elongation factor EF1-A and ensures interaction
      with Met-tRNA(i)(Met). In the presence of the alpha subunit, which is composed of
      three domains, the gamma subunit expresses full tRNA binding capacity. This study
      reports the crystallographic structure of the intact aIF2alpha subunit from the
      archaeon Pyrococcus abyssi and that of a derived C-terminal fragment containing
      domains 2 and 3. The obtained structures are compared with those of N-terminal
      domains 1 and 2 of yeast and human eIF2alpha and with the recently determined NMR
      structure of human eIF2alpha. We show that the three-domain organization in the
      alpha subunit is conserved in archaea and eukarya. Domains 1 and 2 form a rigid
      body linked to a mobile third domain. Sequence comparisons establish that the
      most conserved regions in the aIF2alpha polypeptide lie at opposite sides of the
      protein, within domain 1 and domain 3, respectively. These two domains are known
      to exhibit RNA binding capacities. We propose that domain 3, which is known to
      glue the alpha subunit onto the gamma subunit, participates in Met-tRNA(i)(Met)
      binding while domain 1 recognizes either rRNA or mRNA on the ribosome. Thereby,
      the observed structural mobility within the e- and aIF2alpha molecules would be
      an integral part of the biological function of this subunit in the heterotrimeric
      e- and aIF2alphabetagamma factors.

PMID- 15952782
TI  - Cysteine residues in the human cannabinoid receptor: only C257 and C264 are
      required for a functional receptor, and steric bulk at C386 impairs antagonist
      SR141716A binding.
AB  - The human neuronal cannabinoid receptor (CB1) is a G-protein-coupled receptor
      (GPCR) triggered by the psychoactive ingredients in marijuana, as well as
      endogenous cannabinoids produced in the brain. As with most GPCRs, the mechanism
      of CB1 activation is poorly understood. In this work, we have assessed the role
      of cysteine residues in CB1 ligand binding and activation, and demonstrate a
      method for mapping key determinants in CB1 structure and function. Through
      mutational analysis, we find that only two cysteines, C257 and C264, are required
      for high-level expression and receptor function. In addition, through cysteine
      reactivity studies, we find that a cysteine in transmembrane helix seven, C386
      (C7.42), is reactive toward methanethiosulfonate (MTS) sulfhydryl labeling
      agents, and is thus solvent accessible. Interestingly, steric bulk introduced at
      this site, either through MTS labeling or by mutation, inhibits binding of the
      antagonist drug SR141716A (also known as Rimonabant or Accomplia), but does not
      affect the binding of the agonist CP55940. Our subsequent modeling studies
      suggest this effect is caused by steric clash of the modified C386 residue with
      the piperidine ring of SR141716A and/or disruption of an aromatic microdomain in
      the binding pocket. On the basis of these results, we hypothesize that bound
      SR141716A inhibits the ability of transmembrane helix 6 to move during formation
      of the functionally active receptor state.

PMID- 15952783
TI  - Main chain and side chain dynamics of the ubiquitin conjugating enzyme variant
      human Mms2 in the free and ubiquitin-bound States.
AB  - Protein ubiquitination involves a cascade of enzymatic steps where ubiquitin (Ub)
      is sequentially transferred as a thiolester intermediate from an E1 enzyme to an
      E2 enzyme and finally to the protein target with the help of a Ub-protein ligase.
      Protein ubiquitination brought about by the Ubc13-Mms2 (E2-E2) complex has a
      unique role in the cell, unrelated to protein degradation. The Mms2-Ubc13
      heterodimer links Ub molecules to one another through an isopeptide bond between
      its own C-terminus and Lys-63 on another Ub. The role of Mms2 is to orient a
      target-bound Ub molecule such that its Lys-63 is proximal to the C-terminus of
      the Ub molecule that is covalently linked to the active site of Ubc13. To gain
      insight into the influence of protein dynamics on the affinity of Ub for Mms2, we
      have determined pico- to nanosecond time scale fluctuations of the main chain and
      methyl side chains of human Mms2 in the free and Ub-bound states using solution
      state (15)N and (2)H nuclear magnetic resonance relaxation measurements. Analysis
      of the relaxation data allows for a semiquantitative estimation of the
      conformational entropy change (TDeltaS(NMR)) for the main chain and side chain
      methyl groups of Mms2 upon binding Ub. The value of TDeltaS(NMR) for the main
      chain and side chain methyl groups of Mms2 is -8 +/- 2 and -2 +/- 2 kcal mol(
      )(1), respectively. The experimental DeltaG(binding) for the Mms2.Ub complex is 
      6 kcal mol(-)(1). Estimation of DeltaG(binding) using an empirical structure
      based approach that does not account for changes in main chain entropy yields a
      value of -17 +/- 2 kcal mol(-)(1). However, inclusion of TDeltaS(NMR) for the
      main chain of Mms2 increases the estimated DeltaG(binding) to -9 +/- 3 kcal mol(
      )(1). Assuming that changes in Ub main chain dynamics contribute to TDeltaS(NMR)
      to the same extent as Mms2, the estimated DeltaG(binding) is further reduced to 
      1 +/- 4 kcal mol(-)(1), a value close to the experimental DeltaG(binding).

PMID- 15952784
TI  - Solution structure of the Ca2+-Binding EGF3-4 pair from vitamin K-dependent
      protein S: identification of an unusual fold in EGF3.
AB  - Vitamin K-dependent protein S is a cofactor of activated protein C, a serine
      protease that regulates blood coagulation. Deficiency of protein S can cause
      venous thrombosis. Protein S has four EGF domains in tandem; domains 2-4 bind
      calcium with high affinity whereas domains 1-2 mediate interaction with activated
      protein C. We have now solved the solution structure of the EGF3-4 fragment of
      protein S. The linker between the two domains is similar to what has been
      observed in other calcium-binding EGF domains where it provides an extended
      conformation. Interestingly, a disagreement between NOE and RDC data revealed a
      conformational heterogeneity within EGF3 due to a hinge-like motion around Glu186
      in the Cys-Glu-Cys sequence, the only point in the domain where flexibility is
      allowed. The dominant, bent conformation of EGF3 in the pair has no precedent
      among calcium-binding EGF domains. It is characterized by a change in the psi
      angle of Glu186 from 160 degrees +/- 40 degrees , as seen in ten other EGF
      domains, to approximately 0 degrees +/- 15 degrees . NOESY data suggest that
      Tyr193, a residue not conserved in other calcium-binding EGF domains (except in
      the homologue Gas6), induces the unique fold of EGF3. However, SAXS data,
      obtained on EGF1-4 and EGF2-4, showed a dominant, extended conformation in these
      fragments. This may be due to a counterproductive domain-domain interaction
      between EGF2 and EGF4 if EGF3 is in a bent conformation. We speculate that the
      ability of EGF3 to adopt different conformations may be of functional
      significance in protein-protein interactions involving protein S.

PMID- 15952785
TI  - Structure and dynamics of the second and third transmembrane domains of human
      glycine receptor.
AB  - A 61-residue polypeptide resembling the second and third transmembrane domains
      (TM23) of the alpha-1 subunit of human glycine receptor and its truncated form,
      both with the wild-type loop linking the two TM domains (the "23" loop), were
      studied using high-resolution NMR. Well-defined domain structures can be
      identified for the TM2, 23 loop, and TM3 regions. Contrary to the popular model
      of a long and straight alpha-helical structure for the pore-lining TM2 domain for
      the Cys-loop receptor family, the last three residues of the TM2 domain and the
      first eight residues of the 23 loop (S16-S26) seem to be intrinsically nonhelical
      and highly flexible even in trifluoroethanol, a solvent known to promote and
      stabilize alpha-helical structures. The six remaining residues of the 23 loop and
      most of the TM3 domain exhibit helical structures with a kinked pi-helix (or a pi
      turn) from W34 to C38 and a kink angle of 159 +/- 3 degrees . The tertiary fold
      of TM3 relative to TM2 is defined by several unambiguously identified long-range
      NOE cross-peaks within the loop region and between TM2 and TM3 domains. The 20
      lowest-energy structures show a left-handed tilt of TM3 relative to TM2 with a
      tilting angle of 44 +/- 2 degrees between TM2 (V1-Q14) and TM3 (L39-E48) helix
      axes. This left-handed TM2-TM3 arrangement ensures a neatly packed right-handed
      quaternary structure of five subunits to form an ion-conducting pore. This is the
      first time that two TM domains of the glycine receptor linked by the important 23
      loop have ever been analyzed at atomistic resolution. Many structural
      characteristics of the receptor can be inferred from the structural and dynamical
      features identified in this study.

PMID- 15952786
TI  - Solution structure of Kti11p from Saccharomyces cerevisiae reveals a novel zinc
      binding module.
AB  - Kti11p is a small, highly conserved CSL zinc finger-containing protein found in
      many eukaryotes. It was first identified as one of the factors required for
      maintaining the sensitivity of Saccharomyces cerevisiae to Kluyveromyces lactis
      zymocin. Then, it was found to be identical to Dph3, a protein required for
      diphthamide biosynthesis on eEF-2, the target of diphtheria toxin and Pseudomonas
      exotoxin A, in both yeast and higher eukaryotes. Furthermore, Kti11p/Dph3 was
      found to physically interact with core-Elongator, ribosomal proteins, eEF-2, two
      other proteins required for diphthamide modification on eEF-2, and DelGEF. Here,
      we determined the solution structure of Kti11p using NMR, providing the first
      structure of the CSL-class zinc-binding protein family. We present the first
      experimental evidence that Kti11p can bind a single Zn(2+) ion by its four
      conserved cysteine residues. The major structure of Kti11p comprises a beta
      sandwich as well as an alpha helix. Moreover, a structure-based similarity search
      suggests that it represents a novel structure and may define a new family of the
      zinc ribbon fold group. Therefore, our work provides a molecular basis for
      further understanding the multiple functions of Kti11p/Dph3 in different
      biological processes.

PMID- 15952787
TI  - Role of buried polar residues in helix bundle stability and lipid binding of
      apolipophorin III: destabilization by threonine 31.
AB  - Apolipophorin III (apoLp-III) from Locusta migratoria is a model exchangeable
      apolipoprotein that plays a key role in neutral lipid transport. The protein is
      comprised of a bundle of five amphipathic alpha-helices, with most hydrophobic
      residues buried in the protein interior. The low stability of apoLp-III is
      thought to be crucial for lipid-induced helix bundle opening, to allow protein
      lipid interactions. The presence of polar residues in the hydrophobic protein
      interior may facilitate this role. To test this, two buried polar residues, Thr
      31 and Thr-144, were changed into alanine by site-directed mutagenesis. Secondary
      structure analysis and GdnHCl- and temperature-induced denaturation studies
      indicated an increase in alpha-helical content and protein stability for T31A
      apoLp-III compared to wild-type apoLp-III. In contrast, T144A had a decreased
      alpha-helical content and protein stability, while tryptophan fluorescence
      indicated increased exposure of the hydrophobic interior to buffer. Two mutant
      proteins that had lysine residues introduced in the hydrophobic core displayed a
      more pronounced decrease in secondary structure and protein stability. Lipid
      binding studies using phospholipid vesicles showed that T31A apoLp-III was able
      to transform phospholipid vesicles into discoidal particles but at a 3-fold
      reduced rate compared to wild-type apoLp-III. In contrast, the less stable apoLp
      III mutants displayed an increased ability to transform phospholipid vesicles.
      These results demonstrate the inverse correlation between protein stability and
      the ability to transform phospholipid vesicles into discoidal protein-lipid
      complexes and that Thr-31 is a key determinant of the relatively low protein
      stability, thereby promoting apoLp-III to interact with lipid surfaces.

PMID- 15952788
TI  - Influence of the 33 kDa manganese-stabilizing protein on the structure and
      substrate accessibility of the oxygen-evolving complex of photosystem II.
AB  - The 33 kDa manganese-stabilizing extrinsic protein binds to the lumenal side of
      photosystem II (PS II) close to the Mn(4)Ca cluster of the oxygen-evolving
      complex, where it limits access of small molecules to the metal site. Our
      previous finding that the removal of this protein did not alter the magnetic
      coupling regime within the manganese cluster, measured by electron spin-echo
      envelope modulation [Gregor, W., and Britt, R. D. (2000) Photosynth. Res. 65, 175
      185], prompted us to examine whether this accessibility control is also true for
      substrate water, using the same pulsed EPR technique. Comparing the deuteron
      modulation of the S(2)-state multiline signal of PS II membranes, equilibrated
      with deuterated water (D(2)O) after removal or retention of the 33 kDa protein,
      we observed no change in the number and the distance of deuterons magnetically
      coupled to manganese, indicating that the number and distance of water molecules
      bound to the manganese cluster are independent of bound 33 kDa protein in the
      S(1) state, in which the sample was poised prior to cryogenic illumination. A
      simple modulation depth analysis revealed a distance of 2.5-2.6 A between the
      closest deuteron and manganese. These results are in agreement with our refined X
      ray absorption analysis. The manganese K-edge positions, reflecting their
      oxidation states, and the extended X-ray absorption fine structure amplitudes and
      distances between the manganese ions and their oxygen and nitrogen ligands (1.8,
      2.7, and 3.3-3.4 A) were independent of bound 33 kDa protein.

PMID- 15952789
TI  - Magnesium, ADP, and actin binding linkage of myosin V: evidence for multiple
      myosin V-ADP and actomyosin V-ADP states.
AB  - The [Mg(2+)] dependence of ADP binding to myosin V and actomyosin V was measured
      from the fluorescence of mantADP. Time courses of MgmantADP dissociation from
      myosin V and actomyosin V are biphasic with fast observed rate constants that
      depend on the [Mg(2+)] and slow observed rate constants that are [Mg(2+)]
      independent. Two myosin V-MgADP states that are in reversible equilibrium, one
      that exchanges nucleotide and cation slowly (strong binding) and one that
      exchanges nucleotide and cation rapidly (weak binding), account for the data. The
      two myosin V-MgADP states are of comparable energies, as indicated by the
      relatively equimolar partitioning at saturating magnesium. Actin binding lowers
      the affinity for bound Mg(2+) 2-fold but shifts the isomerization equilibrium
      approximately 6-fold to the weak ADP binding state, lowering the affinity and
      accelerating the overall rate of MgADP release. Actin does not weaken the
      affinity or accelerate the release of cation-free ADP, indicating that actin and
      ADP binding linkage is magnesium-dependent. Myosin V and myosin V-ADP binding to
      actin was assayed from the quenching of pyrene actin fluorescence. Time courses
      of myosin V-ADP binding and release are biphasic, consistent with the existence
      of two (weak and strong) quenched pyrene actomyosin V-ADP conformations. We favor
      a sequential mechanism for actomyosin V dissociation with a transition from
      strong to weak actin-binding conformations preceding dissociation. The data
      provide evidence for multiple myosin-ADP and actomyosin-ADP states and establish
      a kinetic and thermodynamic framework for defining the magnesium-dependent
      coupling between the actin and nucleotide binding sites of myosin.

PMID- 15952790
TI  - Identification of tyrosine residues on ELMO1 that are phosphorylated by the Src
      family kinase Hck.
AB  - The SH3 and SH2 domains of hematopoietic cell kinase (Hck) play important roles
      in substrate targeting. To identify new components of Hck signaling pathways, we
      identified proteins that bind to the SH3 domain of Hck (Scott et al. (2002) J.
      Biol. Chem. 277, 28238). One such protein was ELMO1, the mammalian orthologue of
      the Caenorhabditis elegans gene, ced-12. ELMO1 is an approximately 80-kD protein
      containing a PH domain and a C-terminal Pro-rich sequence. In C. elegans, ced-12
      is required for the engulfment of dying cells and for cell migration. In
      mammalian fibroblasts, ELMO1 binds to Dock180, and functions upstream of Rac
      during phagocytosis and cell migration. We previously showed that ELMO1 binds
      directly to the Hck SH3 domain and is phosphorylated by Hck. In this study, we
      used mass spectrometry to identify the following sites of ELMO1 phosphorylation:
      Tyr 18, Tyr 216, Tyr 511, Tyr 395, and Tyr 720. Mutant forms of ELMO1 lacking
      these sites were defective in their ability to promote phagocytosis and migration
      in fibroblasts. Single tyrosine mutations showed that Tyr 511 is particularly
      important in mediating these biological effects. These mutants displayed
      comparable binding to Dock180 and Crk as wild-type ELMO1, but gave a lowered
      activation of Rac. The data suggest that Src family kinase mediated tyrosine
      phosphorylation of ELMO1 might represent an important regulatory mechanism that
      controls signaling through the ELMO1/Crk/Dock180 pathway.

PMID- 15952791
TI  - Factor VIII A3 domain residues 1954-1961 represent an A1 domain-interactive site.
AB  - Factor VIIIa consists of subunits designated A1, A2, and A3C1C2. Reassociation of
      the A1 and A3C1C2 subunits monitored by the factor Xa generation assay and
      fluorescence resonance energy transfer yielded intersubunit affinity values
      (K(d)) of 58.0 +/- 12.5 and 58.8 +/- 16.8 nM, respectively. These affinity values
      were equivalent to that previously determined for factor VIII heavy and light
      chains [Wakabayashi, H., et al. (2001) Biochemistry 40, 10293-10300], suggesting
      that the A2 domain makes a minimal contribution to the interchain affinity in
      factor VIII. Ca(2+) showed no effect on A1/A3C1C2 intersubunit affinity (K(d) =
      51.6 +/- 16.6 nM), while Cu(2+) enhanced the A1/A3C1C2 intersubunit affinity
      approximately 5-fold (K(d) = 12.5 +/- 2.3 nM). A synthetic peptide to A3 domain
      residues 1954-1961 inhibited association of the A1 and A3C1C2 subunits (K(i) =
      65.8 +/- 11.9 microM). Three factor VIII point mutants, His1957Ala, Gly1960Val,
      and His1961Asp, were stably expressed in BHK cells and purified. All mutants
      exhibited reduced specific activity (39, 42, and 4%, respectively) compared with
      that of wild-type factor VIII, and their activity was less stable following heat
      denaturation analysis (t(1/2) values of 13.3 +/- 0.7, 8.7 +/- 0.3, and 8.1 +/-
      0.1 min, respectively) compared with that of the wild type (18.8 +/- 0.8 min).
      This reduced stability appeared to result from an approximately 2-fold increased
      dissociation rate for the Gly1960Val and His1961Asp dimers as judged by solid
      phase binding assays. We propose that residues 1954-1961 of the A3 domain
      contribute to interactions with the A1 domain, facilitating their association in
      factor VIII.

PMID- 15952792
TI  - Identification of the heparin-binding region of snake venom vascular endothelial
      growth factor (VEGF-F) and its blocking of VEGF-A165.
AB  - VEGF-A165 displays multiple effects through binding to KDR (VEGFR-2).
      Heparin/heparan sulfate-like molecules are known to greatly modulate their
      interaction. In fact, VEGF-A lacking a C-terminal heparin-binding region exhibits
      significantly reduced mitogenic activity. We recently found novel heparin-binding
      VEGFs in snake venom, designated VEGF-Fs, which specifically recognize KDR,
      rather than other VEGF receptors. VEGF-Fs virtually lack the C-terminal heparin
      binding region when compared with other heparin-binding VEGF subtypes, despite
      their heparin-binding potential. The C-terminal region does not exhibit any
      significant homology with other known proteins or domains. In this study, we
      attempted to identify the heparin-binding region of VEGF-F using synthetic
      peptides. The C-terminal peptide of vammin (one of the VEGF-Fs, 19 residues)
      bound to heparin with similar affinity as native vammin. We then evaluated the
      effects of this peptide on the biological activity of VEGF-A165. The C-terminal
      peptide of VEGF-F exhibited specific blockage of VEGF-A165 activity both in vitro
      and in vivo. These observations demonstrate that the short C-terminal region of
      VEGF-F functions fully as the active heparin-binding domain and the corresponding
      peptide specifically blocks VEGF-A165, thus suggesting that the C-terminal
      heparin-binding region of VEGF-F recognizes similar heparin/heparan sulfate
      molecules as VEGF-A165. The present results will provide novel insight into VEGF
      heparin interaction and may facilitate the design of new anti-VEGF drugs based on
      novel strategies.

PMID- 15952793
TI  - Density functional theory calculations on the dielectric constant dependence of
      the oxidation potential of chlorophyll: implication for the high potential of
      P680 in photosystem II.
AB  - The primary donor chlorophyll (Chl) of photosystem II (PSII), P680, has an
      extremely high oxidation redox potential (E(ox)) of approximately 1.2 V, which is
      essential for photosynthetic water oxidation. The mechanism for achieving a high
      potential such as that of P680 has been one of the central questions in
      photosynthesis research. Here, we have examined the dielectric constant (epsilon)
      dependence of the E(ox) of monomer Chl using density functional theory
      calculations with the polarizable continuum model. The calculated E(ox) of a
      model Chl compound exhibited a sharp increase with a decrease in epsilon in the
      relatively low epsilon region (epsilon < 5). In contrast, in the higher-epsilon
      region, E(ox) was rather insensitive to epsilon and converged to a constant value
      at very high epsilon values. This tendency in the high-epsilon region explains
      the experimental E(ox) values of isolated Chl a that have been observed in a
      relatively narrow range of 0.74-0.93 V. The E(ox) of Chl in an ideal hydrophobic
      protein was estimated to be approximately 1.4 V at an epsilon value of 2. This
      value indicates that Chl in a hydrophobic environment originally has a high E(ox)
      that is sufficient for oxidizing water (E(ox) = 0.88 V at pH 6). On the basis of
      the reported X-ray crystallographic structures, the protein environment of P680
      in PSII was estimated to be more hydrophobic than that of the primary donors in
      bacterial reaction centers. It is therefore suggested that the low-dielectric
      environment around P680 is one of the major factors in its very high E(ox), and
      thus, introducing nonpolar amino acids into the binding pocket of P680 was an
      important process in the evolution of PSII.

PMID- 15952794
TI  - Lantibiotic structures as guidelines for the design of peptides that can be
      modified by lantibiotic enzymes.
AB  - Lantibiotics are (methyl)lanthionine-containing bacterial peptides.
      (Methyl)lanthionines are posttranslationally introduced into the prepropeptides
      by biosynthetic enzymes that dehydrate serines and threonines and couple these
      dehydrated residues to cysteine residues. Thirty seven lantibiotic primary
      structures have been proposed to date, but little is known about the substrate
      specificity of the lantibiotic modifying enzymes. To define rules for the
      rational design of modified peptides, we compared all known lantibiotic
      structures by in silico analysis. Although no strict sequence motifs can be
      defined that govern the modification, statistical analysis demonstrates that
      dehydratable serines and threonines are more often flanked by hydrophobic than by
      hydrophilic amino acids. Serine residues escape dehydration more often than
      threonines. With these rules, novel hexapeptides were designed that either were
      predicted to become modified or will escape modification. The hexapeptides were
      fused to the nisin leader and expressed in a Lactococcus lactis strain containing
      the nisin modifying and export enzymes. The excreted peptides were analyzed by
      mass spectrometry. All designed fusion peptides were produced, and the presence
      or absence of modifications was found to be in full agreement with the
      predictions based on the statistical analysis. These findings demonstrate the
      feasibility of the rational design of a wide range of novel peptides with
      dehydrated amino acid residues.

PMID- 15952795
TI  - Thermodynamic and in vitro replication studies of an intrastrand G[8-5]C cross
      link lesion.
AB  - We recently identified, from the gamma-irradiation mixture of duplex DNA, a new
      intrastrand G[8-5]C cross-link lesion, in which the C8 atom of guanine and the C5
      atom of its 3' neighboring cytosine are covalently bonded, and carried out in
      vitro replication studies for the lesion-bearing substrate with a translesion
      synthesis polymerase, yeast polymerase eta. Here we extended the in vitro
      replication studies to two replicative polymerases, exonuclease-deficient
      bacteriophage T7 DNA polymerase (T7(-)) and HIV reverse transcriptase (HIV-RT).
      Primer extension assays showed that both polymerases stopped synthesis after
      incorporating a nucleotide opposite the 3'-cytosine in the G[8-5]C lesion. Steady
      state kinetic measurements for nucleotide incorporation opposite the 3'-cytosine
      of the lesion showed that both T7(-) and HIV-RT preferentially incorporated the
      correct nucleotide, dGMP. We also examined the thermal stabilities and base
      pairing properties of G[8-5]C in d(ATGGCG[8-5]CGCTAT). The G[8-5]C lesion
      destabilizes the duplex form by approximately 4 kcal/mol in free energy at 25
      degrees C relative to the undamaged parent duplex, and the thermally most stable
      duplex has natural bases opposite the lesion.

PMID- 15952796
TI  - Phosphorylation of Grb10 by mitogen-activated protein kinase: identification of
      Ser150 and Ser476 of human Grb10zeta as major phosphorylation sites.
AB  - Grb10 is a Src-homology 2 (SH2) and Pleckstrin-homology (PH) domain-containing
      protein that binds to several autophosphorylated receptor tyrosine kinases
      including the insulin receptor (IR). Our previous studies showed that Grb10
      underwent insulin-stimulated serine phosphorylation, yet the kinase(s)
      responsible for phosphorylation and the sites of the phosphorylation remain
      unknown. In this report, we show that Grb10 is a direct substrate of the p42/44
      mitogen-activated protein kinase (MAPK). In addition, we found that inhibition of
      the MAPK signaling pathway reduced Grb10 phosphorylation in cells. Using site
      directed mutagenesis, phosphopeptide mapping, and capillary HPLC-electrospray
      tandem mass spectrometry analysis, we identified Ser(150), Ser(418), and Ser(476)
      of human Grb10zeta as MAPK-mediated in vitro phosphorylation sites. In vivo
      labeling and two-dimensional phosphopeptide mapping studies revealed that
      Ser(150) and Ser(476) of human Grb10zeta are phosphorylated in intact cells.
      Replacing Ser(150) and Ser(476) with alanines reduced the inhibitory effect of
      human Grb10zeta on insulin-stimulated IRS1 tyrosine phosphorylation. Taken
      together, our findings suggest that phosphorylation of the adaptor protein may
      provide a feedback inhibitory mechanism by which Grb10 regulates insulin
      signaling.

PMID- 15952797
TI  - Design of peptidyl compounds that affect beta-amyloid aggregation: importance of
      surface tension and context.
AB  - Self-association of beta-amyloid (Abeta) peptide into cross-beta-sheet fibrils
      induces cellular toxicity in vitro and is linked with progression of Alzheimer's
      disease. Previously, we demonstrated that hybrid peptides, containing a
      recognition domain that binds to Abeta and a disrupting domain consisting of a
      chain of charged amino acids, inhibited Abeta-associated toxicity in vitro and
      increased the rate of Abeta aggregation. In this work we examine the design
      parameter space of the disrupting domain. Using KLVFFKKKKKK as a base case, we
      tested hybrid compounds with a branched rather than linear lysine oligomer, with
      l-lysine replaced by d-lysine, and with lysine replaced by diaminopropionic acid.
      We synthesized a compound with a novel anionic disrupting domain that contained
      cysteine thiols oxidized to sulfates, as well as other compounds in which alkyl
      or ether chains were appended to KLVFF. In all cases, the hybrid compound's
      ability to increase solvent surface tension was the strongest predictor of its
      effect on Abeta aggregation kinetics. Finally, we investigated the effects of
      arginine on Abeta aggregation. Arginine is a well-known chaotrope but increases
      surface tension of water. Arginine modestly decreased Abeta aggregation. In
      contrast, RRRRRR slightly, and KLVFFRRRRRR greatly, increased Abeta aggregation.
      Thus, the influence of arginine on Abeta aggregation depends strongly on the
      context in which it is presented. The effect of arginine, RRRRRR, and KLVFFRRRRRR
      on Abeta aggregation was examined in detail using laser light scattering,
      circular dichroism spectroscopy, Fourier transform infrared spectroscopy,
      thioflavin T fluorescence, and transmission electron microscopy.

PMID- 15952798
TI  - Site-directed mutagenesis and use of bile acid-MTS conjugates to probe the role
      of cysteines in the human apical sodium-dependent bile acid transporter
      (SLC10A2).
AB  - The residues involved in substrate interaction of the human apical sodium
      dependent bile acid transporter (hASBT, SLC10A2) remain undefined. Biochemical
      modification of conserved cysteine residues has suggested their direct
      involvement in hASBT function. In the present study, we developed novel
      methanethiosulfonyl (MTS)-bile salt derivatives and describe their reactivity
      toward hASBT and its mutants. Endogenous Cys residues were subjected to Ala/Thr
      scanning mutagenesis and subsequent exposure to affinity inactivators. We show
      that C51A/T, C105A/T, C144A, and C255A/T are loss-of-function mutations.
      Additionally, C74A/T cell surface expression was abolished suggesting a role in
      protein folding and/or trafficking. C270A remained largely unaffected in the
      presence of 1.0 mM polar and charged MTS reagents (MTSEA, MTSES, and MTSET) and
      retained function similar to wt-hASBT control. However, in the presence of
      synthetic cholyl- and chenodeoxycholyl-MTS analogues, C270A displayed a
      significant decrease in K(T) and J(max). Our findings demonstrate that Cys270 is
      a highly accessible extracellular residue susceptible to thiol modification in
      its native form that remains largely unaffected upon mutation to Ala.
      Consequently, C270A provides an ideal scaffold for cysteine scanning mutagenesis
      studies. Furthermore, the substantial decrease in ligand affinity and maximal
      transport capacity of C270A suggest that C270 may potentially impact, although
      not critically, a putative substrate binding domain of hASBT. Overall, bile acid
      MTS conjugates can serve as novel and powerful tools to probe the role of
      endogenous as well as engineered Cys residues and, ultimately, aid in defining
      their role in the bile acid binding region(s) of hASBT.

PMID- 15952800
TI  - Supramolecular ordering of tripod dyes at the air/water interface.
AB  - Monolayers of 2-(3,4,5-(trisdodecyloxyl)phenyl)[1,3,4]oxadiazole based "tripod"
      dye, P2G, has been studied at the air/water interface with in situ X-ray
      reflectivity. Compression of the disordered Langmuir-Blodgett monolayer film
      induces a transition to a unique ordered phase, representing a supramolecular
      assembly with a unique spatial distribution and orientation of the molecules. At
      low pressure, the molecules having face-on orientation are interdigitated by the
      three arms. After first transition in the pi-A isotherm, the molecular
      conformation is turned into an edge-on orientation, where the molecules are self
      assembled into supramolecular structures.

PMID- 15952801
TI  - Oriented growth of TS-1 zeolite ultrathin films on poly(ethylene oxide) monolayer
      templates.
AB  - Self-assembled monolayers of poly(ethylene oxide) (PEOM) were used as templates
      to direct the nucleation and subsequent oriented growth of TS-1 zeolite thin
      films. The resulting TS-1 zeolite thin films exhibited completely oriented
      crystalline domains with the 010 crystallographic direction parallel to the
      surface normal with a little deformation in the in-plane direction. Remarkably,
      the correlation length of the film is as extremely large as 1700 A (1200 A) in
      the out-of-plane (in-plane) direction. PEOM act as two-dimensional media for the
      nucleation and growth of highly oriented TS-1 zeolite thin films. This study
      demonstrates that the highly oriented TS-1 thin films can be achieved by using
      the inner parts of PEOM as templates.

PMID- 15952802
TI  - Preparation of hollow polymer particles with a single hole in the shell by
      SaPSeP.
AB  - The influence of sodium dodecyl sulfate (SDS) on the shell formation of hollow
      polymer particles prepared by the SaPSeP method, which was proposed by the
      authors for the preparation of micrometer-sized hollow polymer particles, was
      investigated. A single hole was observed in the shell of the hollow particles
      prepared by seeded polymerization of micrometer-sized, monodisperse
      divinylbenzene/p-xylene droplets in aqueous medium in the presence of SDS at
      concentrations above 43.3 mM, which were prepared by the dynamic swelling method.
      The fraction of the hollow particles having a single hole in the shell and the
      area of the hole increased with the SDS concentration.

PMID- 15952803
TI  - Shape and color of au nanoparticles follow biocatalytic processes.
AB  - The NAD(P)H-mediated growth of Au nanoparticles (NPs) in the presence of ascorbic
      acid, AuCl4-, and cetyltrimethylammonium bromide leads to the formation of shaped
      NP structures consisting of dipods, tripods, and tetrapods. The shaped particles
      exhibit a red-shifted plasmon absorbance at lambda = 680 nm, consistent with the
      existence of a longitudinal plasmon exciton. High-resolution transmission
      electron microscopy analysis of the tripod and tetrapod structures reveals
      directional growth along the <211> and <010> directions, respectively. The shaped
      Au NPs could be generated by a biocatalytic process using alcohol dehydrogenase,
      NAD+, and ethanol, and the resulting blue color provides a colorimetric test for
      ethanol.

PMID- 15952804
TI  - Polymerized vesicles containing molecular recognition sites.
AB  - Vesicles are prepared from diacetylenic peptide amphiphiles that expose a
      molecular recognition site at the surface. The amphiphiles can be polymerized
      using UV light, and the resulting polymeric vesicles exhibit interesting
      chromatic responses that can be used for label-free detection of the interaction
      with a distinct protein in solution.

PMID- 15952805
TI  - Fabrication of gradient colloidal topography.
AB  - A rather simple but yet effective way to self-assemble polystyrene (PS) beads in
      gradient colloidal crystal topography is proposed. The PS bead concentration,
      solvent, and substrate have a big effect on the colloidal crystal topography.
      Whether the gradient-shaped crystals can form or not depends on the Bond number
      [Bo; the ratio of gravitational potential energy (G) to adhesive energy (E(a)),
      or gravitational to capillary forces]. When Bo < 1, that is, the capillary force
      dominates over the gravitational force, the liquid meniscus is stable. The
      gradient-shaped crystals can form. Otherwise, PS beads form a uniform multilayer
      structure.

PMID- 15952806
TI  - Reversible de-intercalation and intercalation induced by polymer crystallization
      and melting in a poly(ethylene oxide)/organoclay nanocomposite.
AB  - Semicrystalline polymer/layered silicate nanocomposites were prepared by solution
      blending of a low molecular weight poly(ethylene oxide) (PEO) with an organically
      modified montmorillonite, Cloisite 10A (C10A). The intercalation morphology was
      studied by temperature-dependent synchrotron wide-angle X-ray diffraction (WAXD).
      Unlike PEO homopolymers, significant secondary crystallization was observed in
      the PEO/C10A nanocomposites. Reversible de-intercalation and intercalation
      processes were detected during secondary crystallization and subsequent melting
      of secondary crystals. On the basis of two-dimensional WAXD results on oriented
      samples, an interphase layer between the silicate primary particles and PEO
      lamellar crystals was proposed. Secondary PEO crystallization in the interphase
      regions was inferred to be the primary driving force for polymer chains to
      diffuse out of the silicate gallery. This study provided a useful method to
      investigate polymer diffusion in nanoconfined spaces, which can be controlled by
      PEO secondary crystallization and melting outside the silicate gallery.

PMID- 15952807
TI  - Cationic DMPC/DMTAP lipid bilayers: local lateral polarization of
      phosphatidylcholine headgroups.
AB  - We investigated the effect of dimyristoyltrimethylammonium propane (DMTAP) charge
      on area per molecule of mixed DMTAP/dimyristoylphosphatidylcholine (DMPC)
      bilayers in a simple model. Assuming that trimethylammonium (TAP) charge causes
      lateral polarization of neighboring PC molecules, we analyzed variation in area
      per molecule as the mole fraction of TAP increases. The theoretical predictions
      obtained in the present study are consistent with results of a recent molecular
      dynamics simulation study (Gurtovenko et al. Biophys. J. 2004, 86, 3461).

PMID- 15952808
TI  - TX-100/water/1-butyl-3-methylimidazolium hexafluorophosphate microemulsions.
AB  - Both ionic liquids and water are typical green solvents. In this work, the phase
      behavior of the ternary system consisting of ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate (bmimPF6), TX-100, and water was determined
      at 25.0 degrees C. The water-in-bmimPF6, bicontinuous, and bmimPF6-in-water
      microregions of the microemulsions were identified by cyclic voltammetry method
      using potassium ferrocyanide K4Fe(CN)6 as the electroactive probe. Dynamic light
      scattering (DLS) and the UV-vis method were used to characterize the
      microemulsions. It was demonstrated that the hydrodynamic diameter (Dh) of the
      bmimPF6-in-water microemulsions is nearly independent of the water content but
      increases with increasing bmimPF6 content due to the swelling of the micelles by
      the ionic liquid. The UV-vis further confirmed the existence of water domains in
      the water-in-bmimPF6 microemulsions, and the salt potassium ferricyanide
      K3Fe(CN)6 could be dissolved in the water domains.

PMID- 15952809
TI  - Chemical imaging in a surface forces apparatus: confocal raman spectroscopy of
      confined poly(dimethylsiloxane).
AB  - Confocal Raman spectroscopy has been implemented within the molecularly thin
      films of a surface forces apparatus. Applying this technique to an initial
      system, we investigate the confinement and shear-induced changes in the Raman
      spectra of poly(dimethylsiloxane) (PDMS) liquids confined between atomically
      smooth mica surfaces at thicknesses less than the unperturbed radius of gyration
      of the polymer. We focus on stretch vibrations of the PDMS methyl group, whose
      net orientation is perpendicular to the chain backbone. When PDMS was confined to
      a thickness of approximately the unperturbed radius of gyration (3.5 nm) but no
      shear, the Raman intensity of the methyl group was anisotropic in the x-y plane,
      signifying that chains oriented preferentially parallel to the confining
      surfaces. Relative to the bulk fluid, the relative intensity of the asymmetric to
      symmetric carbon-hydrogen stretch (2965 and 2907 cm-1, respectively) was
      enhanced, indicating that asymmetric vibration was enhanced by confinement.
      Measurements using polarized radiation showed coherent planar anisotropy in the x
      y plane whose direction varied stochastically from experiment to experiment. It
      seems that although coherent in-plane alignment was favored, no preferential
      alignment direction was favored in the absence of shear. Application of shear
      caused the time-averaged polymer conformations to become more nearly isotropic in
      the plane of shear. These measurements are considered to represent the first
      chemical imaging of chemical species within the contact area of a surface forces
      apparatus.

PMID- 15952810
TI  - Synthesis of tetraoctylammonium-protected gold nanoparticles with improved
      stability.
AB  - This paper shows that an introduction of thiosulfate anions in place of bromide
      anions greatly improves both chemical and thermal stability of tetraoctylammonium
      protected gold nanoparticles. Tetraoctylammonium thiosulfate [(Oct)4N+-O3SS]
      protected gold nanoparticles are synthesized by the reduction of (Oct)4N+-AuCl4
      to Au(I)-SSO3-, followed by the addition of sodium borohydride. The presence of
      thiosulfate anions instead of bromide anions on the surface of gold nanoparticles
      results in a significant dampening of the surface plasmon band of gold at 526 nm
      due to the strong interaction between thiosulfate and the gold nanoparticle
      surface. Cyanide decomposition and heating treatment studies suggest that
      (Oct)4N+-O3SS-protected nanoparticles have much higher overall stability compared
      to (Oct)4N+-Br-protected gold nanoparticles.

PMID- 15952811
TI  - Structural changes of the gold-support interface during CO oxidation catalyzed by
      mononuclear gold complexes bonded to zeolite NaY: evidence from time-resolved X
      ray absorption spectroscopy.
AB  - Mononuclear gold complexes synthesized from AuIII(CH3)2(acac) in zeolite NaY were
      characterized by time-resolved X-ray absorption spectroscopy and infrared
      spectroscopy as they catalyzed CO oxidation at 298 K and 760 Torr in flow
      systems. Initial contact with a CO + O2 mixture led to the rapid formation of
      cationic gold complexes in which Au was bonded to approximately two zeolite O
      atoms, on average. Further contact with CO + O2 led to breaking of an Au-surface
      oxygen bond, giving a gold carbonyl anchored to approximately one O atom. The
      process was reversed in the absence of CO and O2.

PMID- 15952812
TI  - Surface and aggregation behavior of aqueous solutions of Ru(II)
      metallosurfactants: 4. Effect of chain number and orientation on the aggregation
      of [Ru(bipy)2(bipy')]Cl2 complexes.
AB  - The structure of aggregates formed by eight surfactant [Ru(bipy)2(p,p'-dialkyl
      2,2'-bipy)]Cl2 complexes-which we express as Ru(p)(q)Cn, where n (=12 or 19) is
      the alkyl chain length, p (=4 or 5) refers to the substitution position on the
      bipyridine ligand, and q (=1 or 2) is the number of substituted alkyl chains-in
      aqueous solutions has been examined using small-angle neutron scattering for a
      range of concentrations close to the critical micelle concentration and for
      several combinations of n, p, and q. A number of general results emerge. The
      double-chain surfactants possess a smaller headgroup charge but a larger
      aggregate size than their single-chain analogues. Over the concentration range
      studied, the micelles of the single-chain surfactants grow as the concentration
      is increased, whereas for the double-chain systems, the aggregate size remains
      unchanged. For both single- and double-chain surfactants, an increase in alkyl
      chain length is accompanied by an expected increase in aggregate size and an
      increase in average headgroup charge. The aggregates formed in solutions of
      resolved double-chain complexes are larger than those found in solutions of
      racemic mixtures. The Ru(4)(1)C12 and Ru(5)(1)C12 systems form aggregates with
      high water content. Variation of the substitution position for the single-chain
      surfactants produces dramatic changes in the structure of the micelles. The
      aggregates formed in solutions of Ru(4)(1)C19 and Ru(5)(1)C19 display
      particularly different structures. The Ru(4)(1)C19 system forms essentially
      spherical aggregates. In contrast, in the Ru(5)(1)C19 system, wormlike aggregates
      are formed in which the rigid rodlike sections appear to undergo a transition
      from a noninterdigitated to an interdigitated structure as the concentration is
      increased. For double-chain surfactants, the aggregation number for p = 4
      surfactants is considerably larger than that for p = 5 surfactants.

PMID- 15952813
TI  - Increasing surface charge density induces interdigitation in vesicles of cationic
      amphiphile and phosphatidylcholine.
AB  - Binary vesicles of cationic lipid dihexadecyldimethylammoniumbromide (DHAB) and
      1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) were examined by differential
      scanning calorimetry, fluorescence spectroscopy, and Fourier transform infrared
      spectroscopy. DHAB/DMPC vesicles demonstrate a complex dependence of the main
      transition temperature (T(m)) on their mole proportion of DHAB, with a maximum of
      42 degrees C at X(DHAB) = 0.4. An increase of T(m) at X(DHAB) < 0.4 is explained
      by reorientation of P(-)-N(+) dipoles of the phosphocholine headgroup, resulting
      in tighter packing of the acyl chains, which increases the thermal energy
      required for trans --> gauche isomerization. At X(DHAB) > 0.4, Coulombic
      repulsion between the cationic DHAB headgroups expands the bilayer evident as a
      decrease in T(m) until a plateau of approximately 28 degrees C at 0.7 < or =
      X(DHAB) > or = 0.9 is reached, followed by an increment of T(m) to approximately
      30 degrees C at X(DHAB) > 0.9. The quenching of DPH-PC fluorescence emission and
      the decrease in the ratio of peak height intensities of symmetric and
      antisymmetric -CH(2)- stretching modes suggest an interdigitated phase to form at
      X(DHAB) > 0.6. Interdigitation allows the membrane to accommodate the augmented
      Coulombic repulsion between DHAB headgroups because of increasing cationic
      surface charge density while simultaneously causing tighter packing of the acyl
      chains evident first as a plateau at 0.7 < or = X(DHAB) > or = 0.9 and
      subsequently as an increase in T(m) at X(DHAB) > 0.9. Screening of the membrane
      charges by NaCl abolishes the quenching of DPH emission and decreases T(m), thus
      revealing electrostatic repulsion as the driving force for interdigitation.

PMID- 15952814
TI  - Characterization of the aggregates of N-alkyl-N-methylpyrrolidinium bromide
      surfactants in aqueous solution.
AB  - We have characterized a new class of surfactant molecules using fluorescence
      spectroscopic and light-scattering techniques. Our results suggest that this
      homologous series of N-alkyl-N-methlypyrrolidinium bromide (CnMPB) surfactants
      with n = 10, 12, 14, 16, and 18 represents a bridge between the well
      characterized alkyltrimethylammonium bromide (CnTAB) and dialkyldimethylammonium
      bromide (di-CnDAB) surfactant series. For the smaller members of the CnMPB series
      with n = 10, 12, and 14, our results are consistent with the formation of
      spherical micelles as the surfactant concentration is increased. With increasing
      alkyl chain length, we observe that the critical micelle concentration decreases
      and the aggregation number increases, typical of single-tail surfactants. For
      C16MPB, the formation of micelles at dilute concentrations (0.10 mM) is likely,
      followed by the coexistence of micelles and small unilamellar vesicles at higher
      concentrations up to 0.82 mM where only vesicles are present. For C18MPB, our
      data are consistent with the formation of vesicles only. We demonstrate in this
      study that the combination of spectroscopic and light-scattering methods is a
      powerful approach to reveal aspects of aggregate structure and morphology in
      aqueous CnMPB surfactant systems. In particular, the sensitivity of the
      fluorescence probe prodan to the polarity of its microenvironment enables the
      rich complexity of surfactant aggregates exhibited by this series of amphiphilic
      molecules to be detected.

PMID- 15952815
TI  - Effects of type and physical properties of oil phase on oil-in-water emulsion
      droplet formation in straight-through microchannel emulsification, experimental
      and CFD studies.
AB  - Straight-through microchannel (MC) emulsification is a novel technique for
      formulating monodisperse emulsions using an array of micrometer-sized channels
      vertical to the surface of a silicon plate (a straight-through MC). We studied
      the effects of the type and physical properties of the dispersed oil phase and of
      the surfactant concentration on droplet formation from a straight-through MC by
      experiments and computational fluid dynamics (CFD) simulations. Monodisperse oil
      in-water emulsions with coefficients of variation below 4% were formulated from
      an oblong straight-through MC using silicone oils, tetradecane, medium-chain
      triglyceride, soybean oil, and liquid paraffin as the oil phase. At oil
      viscosities (eta(d)) lower than a threshold value of 100 mPa s, the values of the
      resultant droplet diameter (d(ex)) gradually decreased with increasing eta(d),
      whereas they were not affected by the surfactant concentration. Conversely, at
      eta(d) higher than the threshold value, the d(ex) values significantly increased
      with increasing eta(d), and they were affected by the surfactant concentration.
      An analysis on the basis of droplet formation time and interfacial tension
      clarified that the trends in d(ex) at eta(d) above the threshold value would be
      caused by the significant decrease in the dynamic interfacial tension during
      droplet formation. We thus discovered that the dynamic interfacial tension is
      also a parameter affecting the d(ex) along with eta(d) in straight-through MC
      emulsification. CFD simulations using a three-dimensional (3D) model including a
      straight-through MC confirmed successful formation of micrometer-sized droplets
      for the above-mentioned oils. The experimental and CFD results for the resultant
      droplet size were compared using the dimensionless droplet diameter (d, droplet
      diameter/channel equivalent diameter). The d(CFD) values agreed well with the
      d(ex) values at eta(d) below the threshold value of 100 mPa s for all the
      experiment systems and at eta(d) above the threshold value for the experiment
      systems that did not contain a surfactant.

PMID- 15952816
TI  - Protonation-induced structural change of lyotropic liquid crystals in oley- and
      alkyldimethylamine oxides/water systems.
AB  - Lyotropic phase behavior of the nonionic and the half-ionized oleyldimethylamine
      oxide (OlDMAO)/water systems was investigated using polarized light microscopy,
      small-angle X-ray diffraction, and differential scanning calorimetry. Nonionic
      OlDMAO formed isotropic micellar solution, nematic, hexagonal, cubic, and
      lamellar liquid crystalline phases as the surfactant concentration increased. In
      contrast, half-ionized OlDMAO (i.e., 1:1 mixture of the nonionic and the
      protonated species) had a greater tendency to form bilayer structures, and the
      phase diagram became quite similar to those of double-chained ionic surfactants
      rather than single-chained ones, despite the introduction of positive charges to
      the nonionic one. The preference of the bilayer structures in the half-ionized
      OlDMAO was interpreted in terms of the dimers stabilized by the hydrogen bond
      between the nonionic and protonated species. For alkyldimethylamine oxides with a
      saturated hydrocarbon chain (CnDMAO, chain length: n = 14, 16, and 18), the phase
      sequence of lyotropic liquid crystals was hardly affected by the protonation, but
      an elongation of the cylinders of the hexagonal phase was observed for the half
      ionized C14DMAO. Consequently, it can be considered that the dominant bilayer
      formation of the half-ionized OlDMAO is attributed to the combined effect of the
      hydrogen-bonded dimer formation and the cis-double-bond configuration of the
      alkyl chain.

PMID- 15952817
TI  - Small-angle neutron scattering and theoretical investigation of poly(ethylene
      oxide)-poly(propylene oxide)-poly(ethylene oxide) stabilized oil-in-water
      microemulsions.
AB  - The aim of this study is to determine the effects of oil solutes and alcohol
      cosolvents on the structure of oil-in-water microemulsions stabilized by
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO)
      triblock copolymers. The systems investigated involved the solubilization of
      1,3,5-trimethylbenzene or 1,2-dichlorobenzene by P123 (EO(20)-PO(70)-EO(20))
      pluronic surfactant micelles in water and water + ethanol solvents. The
      structures of these swollen micelles were determined by small-angle neutron
      scattering (SANS). A thermodynamic model was employed to interpret the
      characterization data. The results of the thermodynamic model for micellization
      agreed well with the SANS data from samples of micelles swollen by both oils. The
      model predicted the size of the micelles within 5% accuracy using only one
      fitting parameter, the micelle polydispersity. Ethanol had significantly
      different effects on the polymer micelles that contained solubilized oil compared
      to pure polymer micelles. For pure polymer micelles, the addition of ethanol
      increased the solubility of the polymer and, therefore, decreased the total
      volume fraction of micelles, while for polymer-oil aggregates, ethanol tended to
      have a positive effect on the volume fraction of micelles. SANS results showed
      that the greatest divergence from pure aqueous solvent results occurred at oil
      concentrations above the microemulsion stability limit.

PMID- 15952818
TI  - Microcalorimetric and conductivity studies with micelles prepared from multi
      headed pyridinium surfactants.
AB  - A set of novel single-chain surfactants bearing one (P1), two (P2), and three
      (P3) pyridinium headgroups have been synthesized in an attempt to achieve control
      over the aggregate properties. The critical micellar concentrations (cmc's) and
      the degrees of counterion dissociation (alpha) of micelles of these surfactants
      were determined by conductometry. The cmc and the alpha values increased with
      increase in the number of headgroups of the surfactant. The thermodynamics of
      micellization of these surfactants were investigated by microcalorimetry, and the
      results were compared with that of well-known single-chain/single-headgroup
      surfactant, cetylpyridinium bromide (CPB). The relationship between the cmc of
      surfactant in solution and its free energy of micellization (deltaG(o)m) was
      derived for each surfactant. Exothermic enthalpies of micellization (deltaH(o)m)
      and positive entropies of micellization (deltaS(o)m) were observed for all the
      surfactants. deltaH(o)m values were found to be more negative for CPB than P1,
      and it increased with a negative sign from P1 to P2 and decreased for P3. In
      contrast the deltaS(o)m values decreased with increase in the number of
      headgroups. The deltaG(o)m values progressively became less negative with
      increase in the number of headgroups. This implies that micelle formation becomes
      less favorable as more headgroups are incorporated in the surfactant.

PMID- 15952819
TI  - Production and characterization of oil-in-water emulsions containing droplets
      stabilized by multilayer membranes consisting of beta-lactoglobulin, iota
      carrageenan and gelatin.
AB  - The influence of environmental conditions (pH, NaCl, CaCl2, and temperature) on
      the properties and stability of oil-in-water (O/W) emulsions containing oil
      droplets surrounded by one-, two-, or three-layer interfacial membranes has been
      investigated. Three oil-in-water emulsions were prepared with the same droplet
      concentration and buffer (5 wt % corn oil, 5 mM phosphate buffer, pH 6) but with
      different biopolymers: (i) primary emulsion: 0.5 wt % beta-Lg; (ii) secondary
      emulsion: 0.5 wt % beta-Lg, 0.1 wt % iota-carrageenan; (iii) tertiary emulsion:
      0.5 wt % beta-Lg, 0.1 wt % iota-carrageenan, 0-2 wt % gelatin. The secondary and
      tertiary emulsions were prepared by electrostatic deposition of the charged
      biopolymers onto the surfaces of the oil droplets so as to form two- and three
      layer interfacial membranes, respectively. The stability of the emulsions to pH
      (3-8), sodium chloride (0-500 mM), calcium chloride (0-12 mM), and thermal
      processing (30-90 degrees C) was determined. We found that multilayer emulsions
      had better stability to droplet aggregation than single-layer emulsions under
      certain environmental conditions and that one or more of the biopolymer layers
      could be made to desorb from the droplet surfaces in response to specific
      environmental changes (e.g., high salt or high temperature). These results
      suggest that the interfacial engineering technology used in this study could lead
      to the creation of food emulsions with improved stability to environmental
      stresses or to emulsions with triggered release characteristics.

PMID- 15952820
TI  - Aggregation and charging of colloidal silica particles: effect of particle size.
AB  - We studied systematically aqueous suspensions of amorphous well-characterized
      silica particles by potentiometric titration, electrophoretic mobility, and time
      resolved light scattering. Their charging behavior and aggregation rate constants
      were measured as a function of pH and ionic strength in KCl electrolytes for
      three types of particles of approximately 30, 50, and 80 nm in diameter. The
      charging behavior was consistent with the basic Stern model; the silica particles
      carry a negative charge, and its magnitude gradually increases with increasing pH
      and ionic strength. On the other hand, their early-stage aggregation (or
      coagulation) behavior is complex. The aggregation of the largest particles shows
      features resembling predictions of the Derjaguin, Landau, Verwey, and Overbeek
      (DLVO) theory. On one hand, the rate constant decreases sharply with increasing
      pH at low ionic strengths and attains fast aggregation conditions at high ionic
      strengths. On the other hand, we observe a characteristic slowing down of the
      aggregation at low pH and high ionic strengths. This feature becomes very
      pronounced for the medium and the small particles, leading to a complete
      stabilization at low pH for the latter. Stabilization is also observed at higher
      pH for the medium and the small particles. From these aggregation measurements we
      infer the existence of an additional repulsive force. Its origin is tentatively
      explained by postulating hairy layers of consisting of poly(silicilic acid)
      chains on the particle surface.

PMID- 15952821
TI  - Influence of molecular architecture on the dewetting of thin polystyrene films.
AB  - The control of dewetting for thin polymer films is a technical challenge and of
      significant academic interest. We have used polystyrene nanoparticles to inhibit
      dewetting of high molecular weight, linear polystyrene, demonstrating that
      molecular architecture has a unique effect on surface properties. Neutron
      reflectivity measurements were used to demonstrate that the nanoparticles were
      uniformly distributed in the thin (ca. 40 nm) film prior to high temperature
      annealing, yet after annealing, they were found to separate to the solid
      substrate, a silanized silicon wafer. Dewetting was eliminated when the
      nanoparticles separated to form a monolayer or above while below this surface
      coverage the dewetting dynamics was severely retarded. Blending linear
      polystyrene of similar molecular weight to the polystyrene nanoparticle with the
      high molecular weight polystyrene did not eliminate dewetting.

PMID- 15952822
TI  - Surface-ascension of discrete liquid drops via experimental reactive wetting and
      lattice Boltzmann simulation.
AB  - The reactive-wetting technique is employed to move liquid against gravitational
      force. Experiments have shown that the velocity of an ascending liquid drop is
      constant, unlike the gradual decrease intuitively linked to objects against
      gravitation. The ascending velocity decreases for increasing slope. The maximum
      inclination, or stopping, angle for this particular setup is >25 degrees .
      Computer simulation of a reactive-wetting drop using the lattice Boltzmann method
      is also performed. The results indicate that the method employed is suitable for
      the task, producing most experimentally observable responses. The mass flow of a
      liquid drop under reactive wetting was studied through simulation results, and a
      general description of the reactive-wetting phenomenon was deduced.

PMID- 15952823
TI  - Relationship between scattered intensity and separation for particles in an
      evanescent field.
AB  - We describe measurements of the scattering of visible light from an evanescent
      field by both spherical particles (R = 1-10 mum) that are glued to atomic force
      microscopy (AFM) cantilevers, and by sharp tips (R < 60 nm) that were
      incorporated onto the cantilevers during manufacture. The evanescent wave was
      generated at the interface between a flat plate and an aqueous solution, and an
      atomic force microscope was used to accurately control the separation, h, between
      the particle and the flat plate. We find that, for sharp tips, the intensity of
      scattered light decays exponentially with separation between the tip and the
      plate all the way down to h approximately 0. The measured decay length of
      scattered intensity, delta, is the same as the theoretical decay length of the
      evanescent intensity in the absence of the sharp tip. For borosilicate particles,
      (R = 1-10 mum), the scattering also decays exponentially with separation at large
      separations. However, when the separation is less than roughly 3delta, the
      measured scattering intensity is smaller in magnitude than that which would be
      predicted by extrapolating the exponential decay observed at large separations.
      For these particles, the scattering approximately fits the sum of two
      exponentials. The magnitude of the deviation from exponential at contact was
      roughly 10-15% for R = 1 mum particles and about 30% for larger particles and is
      larger for s-polarized light. Preliminary experiments on polystyrene particles
      shows that the scattering is also smaller than exponential at small separations
      but that the deviation from exponential is larger for p-polarized light. In
      evanescent wave AFM (EW-AFM) the scattering-separation can be calibrated for
      situations where the scattering is not exponential. We discuss possible errors
      that could be introduced by assuming that exponential decay of scattering
      continues down to h = 0.

PMID- 15952824
TI  - Preparation of silica-on-titania patterns with a wettability contrast.
AB  - The preparation of patterned inorganic surfaces consisting of silica (SiO2) and
      titania (TiO2) is described. The approach is based on a combination of standard
      photolithography and plasma-enhanced chemical vapor deposition. Silicon wafers
      coated with a titania layer (40 nm) were patterned by use of a positive
      photoresist and then a thin silica layer (10-40 nm) was plasma-deposited. The
      photoresist was removed by decomposition at 800 degrees C. The inorganic
      patterned surfaces possessed excellent high-temperature resistance. Since the
      silica patches were effectively dehydroxylated during the thermal treatment, the
      patterns consisted of moderately hydrophobic (silica) and hydrophilic (titania)
      domains with a significant wettability contrast (40 degrees for water). The
      surface was further hydrophobized with a self-assembled monolayer of
      fluoroalkylsilane (FAS) and exposed to UV light. The FAS layer was locally
      oxidized on the TiO2 patches and the wettability contrast was maximized to 120
      degrees (the highest possible value on smooth surfaces).

PMID- 15952825
TI  - Fluorescent diazapyrenium films and their response to dopamine.
AB  - Experimental protocols for the preparation of 2,7-diazapyrenium films on glass,
      quartz, and silica in one or two steps have been developed. The one-step
      procedures involve the adsorption of preformed 2,7-diazapyrenium dications with
      trimethoxysilane appendages to the hydroxylated substrates. The two-step
      procedures consist in the formation of interfacial polysiloxanes with pendent
      chloromethyl groups and their subsequent coupling to monoalkylated 2,7
      diazapyrene derivatives. For the modification of the glass slides, the silane
      building blocks have been copolymerized with Si(OEt)4. The transmission
      absorption spectra of the coated glass and quartz slides all reveal the
      characteristic bands of the 2,7-diazapyrenium chromophores. Combustion analyses
      confirm the adsorption of the 2,7-diazapyrenium dications on the silica
      particles. A comparison of the surface coverages of all films indicates that the
      one-step procedures are significantly more efficient than their two-step
      counterparts. Furthermore, the copolymerization of the silane building blocks
      with Si(OEt)4 translates into an increase in 2,7-diazapyrenium surface coverage
      of approximately 1 order of magnitude. The emission and excitation spectra of all
      modified substrates reveal the characteristic bands of the 2,7-diazapyrenium
      fluorophores. The fluorescence quantum yield, however, decreases as the surface
      coverage increases. Presumably, interactions between adjacent fluorophores
      encourage nonradiative deactivation pathways. With the exception of the glass
      slides modified in two steps, all films respond to the presence of dopamine, in
      aqueous environments at neutral pH, with pronounced decreases in emission
      intensity. The association of the 2,7-diazapyrenium acceptors and dopamine donors
      at the solid/liquid interface is responsible for fluorescence quenching. The
      glass slides and silica particles modified in one step are the most sensitive
      substrates and respond to sub-millimolar concentrations of dopamine with large
      changes in emission intensity. Furthermore, their fluorescence is not affected by
      relatively large concentrations of ascorbic acid, which is the main interferent
      in conventional dopamine detection protocols. Thus, these results demonstrate
      that the supramolecular association of 2,7-diazapyrenium dications and pi
      electron rich substrates can be reproduced successfully at solid/liquid
      interfaces and suggest that the unique properties of 2,7-diazapyrenium films
      might lead to dopamine-sensing schemes based on fluorescence measurements.

PMID- 15952826
TI  - Surface analysis of erodible multilayered polyelectrolyte films: nanometer-scale
      structure and erosion profiles.
AB  - Atomic force microscopy (AFM) and scanning electron microscopy (SEM) coupled with
      ellipsometry have been used to characterize the microscale and nanoscale
      structures of erodible multilayered films fabricated from degradable polyamine 1
      and either sodium poly(styrene sulfonate) (SPS) or plasmid DNA. Striking
      differences were found in the topography, structures, and erosion profiles of
      these two materials upon incubation in PBS buffer at 37 degrees C. For films
      fabricated from SPS, AFM data are consistent with an erosion process that occurs
      uniformly without the generation of holes or pits over large, micrometer-scale
      areas. By contrast, films fabricated from plasmid DNA undergo structural
      rearrangements to present surface-bound particles ranging in size from 50 to 400
      nm. Additional characterization of these particulate structures by SEM suggested
      that they are interpenetrated with or fused to underlying polyelectrolyte layers
      on the silicon surface, providing a potential mechanism to manipulate the
      adhesive forces with which these particles are bound to the surface. The erosion
      profile observed for polymer 1/SPS films suggests that it may be possible to
      design assemblies that release two film components with well-defined release
      kinetics. In the context of gene delivery, the presentation of condensed DNA as
      nanoparticles at these surfaces may be advantageous with respect to stimulating
      the internalization and processing of DNA by cells. A quantitative understanding
      of the factors influencing the fabrication, structure, and erosion profiles of
      these materials will be useful for the design of multilayered assemblies for
      specific applications in which controlled film erosion or the release of
      therapeutic materials is desired.

PMID- 15952827
TI  - Encapsulation of polystyrene latex with temperature-responsive poly(N
      isopropylacrylamide) via a self-assembling approach and the adsorption behaviors
      therein.
AB  - Temperature-responsive poly(N-isopropylacrylamide) (PNIPAm)-encapsulated
      polystyrene latex was prepared via a layer-by-layer self-assembly of cationic and
      anionic polyNIPAms alternately. Studies showed that the size of PNIPAm
      encapsulated polystyrene particles (m-PS) increased with the encapsulation
      manipulation, as verified by both transmission electron microscopy and dynamic
      light scattering measurements. The m-PS underwent a dramatic volume decrease at
      the lower critical solution temperature (LCST) of PNIPAm, with the onset
      temperature shifting to a higher temperature range as the number of encapsulating
      layers increased. A qualitative study on the adsorption behavior of Ag
      nanoparticles revealed that while the pristine (p) Ag nanoparticles were
      predominantly adsorbed on the m-PS below the LCST, the hydrophobically modified
      one (m-Ag) was preferentially adsorbed on the same PS above the LCST, which
      corresponded to the hydrophilic to hydrophobic transition of the m-PS at the
      LCST.

PMID- 15952828
TI  - Dewetting induced by complete versus nonretarded van der Waals forces.
AB  - Spontaneous rupture of some polymer films upon heating is commonplace. The very
      criterion for this instability is the system free energy, G(L), possessing a
      negative curvature. In films that are apolar with h < or = 100 nm van der Waals
      (vdW) interactions usually constitute a major contribution to G(L) for which the
      approximate form G(L) = -A/12piL(2) (where A is the Hamaker constant), ignoring
      retardation, has been widely used. In this work, we investigate the limits to
      this approximation by calculating the complete vdW interactions for popular
      polymer film systems in dewetting experiments including air-polystyrene-SiO2-Si,
      air-polystyrene-poly(methyl methacrylate)-Si, and air-poly(methyl methacrylate)
      polystyrene-Si based on the theory of Dzyaloshinskii, Lifshitz, and Pitaevskii
      (DLP). We found that retardation effects could produce significant modifications
      to G(L) even when the thickness of the polymer and/or the interlayer is only 1-2
      nm, contrary to conventional presumption.

PMID- 15952829
TI  - Effect of Laponite and a nonionic polymer on the absorption character of cationic
      dye solutions.
AB  - The effect of Laponite and an amphiphilic triblock copolymer of poly(ethylene
      oxide) (PEO)-poly(propylene oxide) (PPO)-poly(ethylene oxide) (PEO) (PEO(99)
      PPO(65)-PEO(99), and labeled F127) on the absorption character of two cationic
      dyes, methylene blue and toluidine blue O, was studied and interpreted in terms
      of the changing state of aggregation of the dye molecules. The combined effect of
      the polymer and Laponite on dye absorption was significantly different from their
      individual influences. Specifically, the presence of Laponite resulted in an
      increase in monomer population by dispersing the dye on the silicate surface. The
      presence of F127 also resulted in an increase in the dye monomer population,
      although to a smaller extent. The combined effect of the polymer and Laponite was
      an increase in the dimer or aggregate populations attributed to the competition
      of F127 with the dye molecules for the silicate surface.

PMID- 15952830
TI  - Effects of degassing and ionic strength on AFM force measurements in
      octadecyltrimethylammonium chloride solutions.
AB  - Sakamoto et al. (Langmuir 2002, 18, 5713) conducted AFM force measurements
      between silica sphere and fused-silica plate in aqueous
      octadecyltrimethylammonium chloride (C18TACl) solutions and concluded that long
      range attractive force is not observed in carefully degassed solutions. In the
      present work, AFM force measurements were conducted by following the procedures
      described by Sakamoto et al. The results showed the presence of an attractive
      force that was much stronger than the van der Waals force both in air-saturated
      and degassed solutions. The force was most attractive at 5 x 10(-6) M C18TACl,
      where contact angle was maximum. At this concentration, which is close to the
      charge compensation point (ccp) of the glass sphere, the long-range decay lengths
      (D) were 34 and 38 nm in air-saturated and degassed solutions, respectively. At
      10(-5) M, the decay length decreased from 30 to 4 nm upon degassing. This
      decrease in decay length can be explained by a pH increase (from 5.7 to 6.6),
      which in turn causes additional surfactant molecules to adsorb on the surface
      with inverse orientation. The attractive force was screened by an added
      electrolyte (NaCl), indicating that the attractive force may be of electrostatic
      origin. Therefore, the very long decay lengths observed in the absence of
      electrolyte may be ascribed to the fact that the ccp occurs at a very low
      surfactant concentration.

PMID- 15952831
TI  - Ionic channel behavior of modified cyclodextrins inserted in lipid membranes.
AB  - We study the insertion and behavior of modified amphiphilic cyclodextrins in
      suspended bilayer lipid membranes by electrophysiological methods. We observe
      that our molecules build single well-defined ionic channels. The pore conductance
      is measured in two lipid membranes differing by their composition. These
      measurements reveal two distinct behaviors. In the case of thin membranes, we
      observe single channels, whereas in the case of thick membranes, we only detect a
      large number of aggregated channels. In a few experiments, we have been able to
      monitor the transition between the two behaviors by modifying slightly the
      swelling of the lipid bilayers by decane. The precise structure of the channels
      is yet unknown; however, we deduce from our measurements an estimation of the
      channel diameter.

PMID- 15952832
TI  - Concentration dependence of the methane structure in silicalite-1: a molecular
      dynamics study using the Moller-Plesset-based potential.
AB  - Moller-Plesset perturbation-based potentials have been used in molecular dynamics
      simulations to examine methane diffusion in silicalite-1. The simulation box
      contains 2 unit cells of silicalite-1 and varying loading numbers (n(ld)) from 1,
      2, 3, to 4 methane molecules per intersection, corresponding to 8, 16, 24, and 32
      molecules per simulation box, respectively. Consistent with the previous study, a
      preferential diffusing path for methane is close to the channel axes. The
      structure of the methane molecules in the silicalite-1 pore was exhibited in
      terms of the methane-methane radial distribution function (RDF) in which the
      first peak appears at 6.4 A for n(ld) < or = 2, becomes a broad maximum at n(ld)
      = 3, and splits into two sharp peaks centered at 6.4 and 8.6 A at n(ld) = 4. This
      fact can be clearly described by an intensification of the methane density in the
      straight and zigzag channels but a decrease in the intersection when the loading
      increases. These features of the observed RDFs are in contrast with the previous
      report using a molecular dynamics force-field potential in which the RDFs for all
      concentrations show first maxima at approximately 4 A. The analysis of the
      relative residence times of methane at different sites inside the silicalite
      suggests that the zigzag channel is the most favored location. The computed self
      diffusion coefficients as well as the heat of adsorptions are in reasonable
      agreement with the available values.

PMID- 15952833
TI  - Adsorption and interaction of fibronectin and human serum albumin at the liquid
      liquid interface.
AB  - The goal of this work was to investigate the dynamics of human plasma fibronectin
      (HFN) at the oil-water interface and to characterize its interactions with human
      serum albumin (HSA) by total internal reflection fluorescence microscopy (TIRFM).
      Among key results, we observed that fibronectin adsorption at the oil-water
      interface is rapid and essentially irreversible, even over short time scales.
      This may be due to the highly flexible nature of the protein, which allows its
      various domains to quickly attain energetically favorable conformations. On the
      other hand, HSA adsorption at the oil-water interface is relatively reversible at
      short times, and the protein is readily displaced by fibronectin even after HSA
      has been adsorbed at the interface for as long as 2 h. At longer adsorption
      times, HSA is able to more effectively resist complete displacement by
      fibronectin, although we observed significant fibronectin adsorption even under
      those conditions. Displacement of adsorbed fibronectin by HSA was negligible
      under all conditions. Fibronectin also adsorbs preferentially from a mixture of
      HFN and HSA, even when the concentration of HSA is substantially higher. This
      study is relevant to such emerging research thrusts as the development of
      biomimetic interfaces for a variety of applications, where there is a clear need
      for better understanding of the effects of interfacial competition, adsorption
      time scales, and extent of adsorption irreversibility on interfacial dynamics.

PMID- 15952834
TI  - Facile synthesis of mesoporous silica sublayer with hierarchical pore structure
      on ceramic membrane using anionic polyelectrolyte.
AB  - A facile method for introducing mesoporous silica sublayer onto the surface of a
      ceramic membrane for use in liquid-phase separation is described. To reduce the
      electrostatic repulsion between the mesoporous silica sol and the ceramic
      membrane in highly acidic conditions (pH < 2), thus facilitating the approach of
      hydrolyzed silica sol to the surface of the membrane, poly(sodium 4
      styrenesulfonate) (Na+PSS-, denoted as PSS-) was used as an ionic linker. The use
      of PSS- led to a significant reduction in positive charge on the ceramic
      membrane, as confirmed by experimental titration data. Consistent with the
      titration results, the amount of mesoporous silica particles on the surface of
      the ceramic membrane was low, in the absence of PSS- treatment, whereas
      mesoporous silica sublayer with hierarchical pore structure was produced, when 1
      wt % PSS- was used. The results show that mesoporous silica grows in the confined
      surface, eventually forming a multistacked surface architecture. The mesoporous
      silica sublayer contained uniform, ordered (P6 mm) mesopores of ca. 7.5 nm from
      mesoporous silica as well as macropores ( approximately mum) from interparticle
      voids, as evidenced by transmission electron microscopy and scanning electron
      microscopy analyses. The morphologies of the supported mesoporous silica could be
      manipulated, thus permitting the generation of uniform needlelike forms or
      uniform spheroid particles by varying the concentration of PSS-.

PMID- 15952835
TI  - In situ layer-by-layer film formation kinetics under an applied voltage measured
      by optical waveguide lightmode spectroscopy.
AB  - Layer-by-layer (LbL) thin film assembly occurs via the alternate adsorption of
      positively and negatively charged macromolecular species. We investigate here the
      control of LbL film growth through the electric potential of the underlying
      substrate. We employ optical waveguide lightmode spectroscopy (OWLS) to obtain in
      situ kinetic measurements of poly(allylamine hydrochloride)/poly(sodium 4
      styrenesulfonate) (PAH/PSS) and poly(L-lysine)/dextran sulfate (PLL/DXS)
      multilayer film formation in the presence of an applied voltage difference
      (deltaV) between the adsorbing substrate, an indium tin oxide- (ITO-) coated
      waveguiding sensor chip, and a parallel platinum counterelectrode. We find
      initial layer adsorption to be significantly enhanced by an applied potential for
      both polyelectrolyte systems: the mass and thickness of (positively charged) PAH
      and PLL layers on ITO are about 60% and 500% larger, respectively, at deltaV = 2
      V than at open circuit potential (OCP), in apparent violation of electrostatics.
      A kinetic analysis reveals the initial attachment rate constant to decrease with
      voltage, in agreement with electrostatics. To reconcile these results, we propose
      a more coiled and loosely bound adsorbed polymer conformation at higher applied
      potential. Following 10 adsorption steps, the mass and thickness of a PAH/PSS
      film grown under deltaV = 2 V are about 15% less than those of a comparable film
      grown under OCP, reflecting a lower degree of complexation between adsorbing
      polyanions and more highly coiled adsorbed polycations. Following 14 adsorption
      steps, the mass and thickness of a PLL/DXS film grown under deltaV = 2 V are
      about 70% greater than those of a comparable film grown under OCP, reflecting the
      increased charge overcompensation in the initial layer. We find the scaling of
      film mass () with the number of adsorption steps (n) to be linear in the PAH/PSS
      system and exponential (i.e., approximately eyn) in the PLL/DXS system,
      irrespective of applied voltage. We observe to decrease with applied voltage and
      to exhibit a crossover to a smaller value around n = 5. Extrapolation reveals
      PLL/DXS multilayer films to be suppressed by increased voltage in the limit of
      large n: the mass of films grown at OCP and deltaV = 1 V would surpass that of a
      film grown under deltaV = 2 V at about the 23rd and 18th adsorption steps,
      respectively. The formation kinetics of PLL/DXS, but not PAH/PSS, change
      qualitatively under voltage: PLL adsorption is slow to reach a plateau, possibly
      due to the formation of secondary structure, and a decrease in film mass occurs
      toward the end of each DXS adsorption step, suggesting spontaneous removal of
      some PLL/DXS complexes from the film.

PMID- 15952836
TI  - Equilibrium aspects of polycation adsorption on silica surface: how the adsorbed
      layer responds to changes in bulk solution.
AB  - Adsorption of cationic high molecular weight polyacrylamides (CPAM) (M(w) is
      about 800 kDa) with different fractions of cationic units tau = 0.09 and tau =
      0.018 onto silica surface was studied over a wide range of pH (4-9) and KCl
      concentration (c(s) = 10(-3)-10(-1) M) by in-situ null ellipsometry. We discuss
      how the adsorbed layer depends on the bulk conditions as well as kinetically
      responds to changes in solution conditions. The adsorbed amount Gamma of CPAM
      increases with pH for all studied electrolyte concentrations until a plateau
      Gamma is reached at pH > 6. At low pH we observed an increase in adsorbed amount
      with electrolyte concentration. At high pH there is no remarkable influence of
      added salt on the values of the adsorbed amount. The thickness of adsorbed
      polymer layers, obtained by ellipsometry, increases with electrolyte
      concentration and decreases with pH. At low c(s) and high pH the polyelectrolyte
      adsorbs in a flat conformation. An overcompensation of the surface charge (charge
      reversal) by the adsorbed polyelectrolyte is observed at high c(s) and low pH. To
      reveal the reversibility of the polyelectrolyte adsorption with respect to the
      adsorbed amount and layer thickness, parameters such as polyelectrolyte
      concentration (c(p)), c(s), and pH were changed during the experiment. Generally,
      similar adsorbed layer properties were obtained independent of whether adsorption
      was obtained directly to initially bare surface or by changing pH, c(s), or the
      concentration of polyelectrolyte solution in the presence of a preadsorbed layer,
      provided that the coverage of the preadsorbed layer was low. Once a steady state
      of the measured parameters (Gamma, d) was reached, experimental conditions were
      restored to the original values and corresponding changes in Gamma and adsorbed
      layer thickness were recorded. For initially low surface coverage it was
      impossible to restore the layer properties, and in this case we always ended up
      with higher coverage than the initial values. For initial high surface coverage
      it was usually possible to restore the initial layer properties. Thus, we
      concluded that polyelectrolyte appears only partially reversible to changes in
      the solution conditions due the slow rearrangement process within the adsorbed
      layer.

PMID- 15952837
TI  - Surface and capillary forces encountered by zinc sulfide microspheres in aqueous
      electrolyte.
AB  - The colloid probe technique was used to investigate the interactions between
      individual zinc sulfide (ZnS) microspheres and an air bubble in electrolyte
      solution. Incorporation of zinc ions into the electrolyte solution overcomes the
      disproportionate zinc ion dissolution and mimics high-volume-fraction conditions
      common in flotation. Determined interaction forces revealed a distinct lack of
      long-ranged hydrophobic forces, indicated by the presence of a DLVO repulsion
      prior to particle engulfment. Single microsphere contact angles were determined
      from particle-bubble interactions. Contact angles increased with decreasing radii
      and with surface oxidation. Surface modification by the absorption of copper and
      subsequently potassium O-ethyldithiocarbonate (KED) reduced repulsive forces and
      strongly increased contact angles.

PMID- 15952838
TI  - Solvent-dependent assembly of terphenyl- and quaterphenyldithiol on gold and
      gallium arsenide.
AB  - The assembly of terphenyldithiol (TPDT) and quaterphenyldithiol (QPDT) on gold
      and gallium arsenide from ethanol (EtOH), tetrahydrofuran (THF), and solutions
      consisting of both solvents has been characterized by near-edge X-ray absorption
      fine structure spectroscopy. The surface coverage and the average orientation of
      both TPDT and QPDT on gold are solvent-independent. These molecules readily form
      monolayers on gold with an ensemble-average backbone tilt of 30 degrees +/- 3
      degrees from the substrate normal. In sharp contrast, the assembly of TPDT and
      QPDT on gallium arsenide is extremely solvent-sensitive. At high ethanol
      fractions, both molecules form monolayers with an ensemble-average orientation
      that is indistinguishable from those on gold substrates. At low ethanol fractions
      and in pure THF, however, these molecules are disordered on gallium arsenide and
      the surface coverage is poor.

PMID- 15952839
TI  - Effect of metal ions on monolayer collapses.
AB  - A Langmuir monolayer of stearic acid on pure water and in the presence of certain
      divalent metal ions such as Cd and Pb at pH approximately 6.5 of the subphase
      water collapses at constant area, while for other divalent ions such as Mg, Co,
      Zn, and Mn at the same subphase pH the monolayer collapses nearly at constant
      pressure. Films of stearic acid with Cd, Pb, Mn, and Co in the subphase (at pH
      approximately 6.5) have been transferred onto hydrophilic Si(001) using a
      horizontal deposition technique, just after and long after collapse. Electron
      density profiles obtained from X-ray reflectivity analysis show that a three
      molecular-layer structure starts to form just after constant area collapse, where
      in the lowest molecular layer, in contact with the substrate, molecules are in
      asymmetric configuration, i.e., both hydrocarbon tails are on the same side of
      the metal-bearing headgroup that touches the substrate, while the molecules above
      the first layer are in symmetric conformation of the tails with respect to the
      headgroups. Further along collapse, when the surface pressure starts to rise
      again with a decrease in area, more layers with molecules in the symmetric
      configuration are added, but the coverage is poor. On the other hand, only
      bimolecular layers form after constant pressure collapse, with the lower and
      upper layers having molecules in asymmetric and symmetric configurations,
      respectively, and the upper molecular layer density increases with compression of
      the monolayer after collapse. A "Ries mechanism" for constant area collapse and a
      "folding and sliding mechanism" for constant pressure collapse have been
      proposed.

PMID- 15952840
TI  - Langmuir and langmuir-blodgett films of metallosupramolecular polyelectrolyte
      amphiphile complexes.
AB  - A detailed analysis of a metallosupramolecular polyelectrolyte-amphiphile complex
      (PAC) at the air-water interface is presented. Langmuir isotherms, Brewster angle
      microscopy, and X-ray reflectance and diffraction methods are employed to
      investigate the structure of the Langmuir monolayers. The PAC is self-assembled
      from 1,3-bis[4'-oxa-(2,2':6',2' '-terpyridinyl)]propane, iron acetate, and
      dihexadecyl phosphate (DHP). Spreading the PAC at the air-water interface results
      in a monolayer that consists of two strata. DHP forms a monolayer at the top of
      the interface, while the metallosupramolecular polyelectrolyte is immersed in the
      aqueous subphase. Both strata are coupled to each other through electrostatic
      interactions. The monolayers can be transferred onto solid substrates, resulting
      in well-ordered multilayers. Such multilayers are model systems for well-ordered
      metal ions in two dimensions.

PMID- 15952841
TI  - Electrodeposition of manganese and molybdenum mixed oxide thin films and their
      charge storage properties.
AB  - Manganese and molybdenum mixed oxides in a thin film form were deposited
      anodically on a platinum substrate by cycling the electrode potential between 0
      and +1.0 V vs Ag/AgCl in aqueous manganese(II) solutions containing molybdate
      anion (MoO(4)2-). A possible mechanism for the film formation is as follows.
      First, electrooxidation of Mn2+ ions with H2O yields Mn oxide and protons. Then,
      the protons being accumulated near the electrode surface react with MoO(4)2- to
      form polyoxomolybdate through a dehydrated condensation reaction (by protonation
      and dehydration). The condensed product coprecipitates with the Mn oxide. Cyclic
      voltammetry of the Mn/Mo oxide film-coated electrode in aqueous 0.5 M Na2SO4
      solution exhibited a pseudocapacitive behavior with higher capacitance and better
      rate capability than that of the pure Mn oxide prepared similarly, most likely as
      a result of an increase in electrical conductivity of the film. Electrochemical
      quartz crystal microbalance and X-ray photoelectron spectroscopy clearly
      demonstrated that the observed pseudocapacitive behavior results from reversible
      extraction/insertion of hydrated protons to balance the charge upon
      oxidation/reduction of Mn3+/Mn4+ in the film.

PMID- 15952842
TI  - Electrostatic stabilization of colloids in carbon dioxide: electrophoresis and
      dielectrophoresis.
AB  - Over the past decade, steric stabilization has been achieved for a variety of
      inorganic and organic colloids in supercritical fluid carbon dioxide (scCO2).
      Herein we demonstrate that colloids may also be stabilized in CO2 by
      electrostatic forces, despite the ultralow dielectric constant of 1.5. Zeta
      potentials of micrometer-sized water droplets, measured in a microelectrophoresis
      cell, reached -70 mV corresponding to a few elementary charges per square
      micrometer of droplet surface. This degree of charge was sufficient to stabilize
      water/CO2 emulsions for an hour, even with water volume fractions of 5%. Hydrogen
      ions partition preferentially, relative to bicarbonate ions, from the emulsion
      droplets to the cores of surfactant micelles in the diffuse double layer
      surrounding the droplets. The micelles, formed with a low molecular weight
      branched hydrocarbon surfactant, prevent ion pairing of the hydrogen counterions
      to the negatively charged emulsion droplets. Dielectrophoresis of the water
      droplets at a frequency of 60 Hz leads to chains containing a dozen droplets with
      lengths of 50 mum. The ability to form electrostatically stabilized colloids in
      carbon dioxide is particularly useful in practical applications, because steric
      stabilization in CO2 is often limited by the poor solvation of the stabilizers.

PMID- 15952843
TI  - Electrochemical self-assembly of melanin films on gold.
AB  - An electrochemical method for self-assembling melanin films on the Au(111)
      surface from melanin aggregates in alkaline media is reported. Electrochemical
      data combined with scanning tunneling microscopy (STM), atomic force microscopy,
      and Auger electron spectoscopy show that the amount and structure of the
      deposited melanin film depend on the potential (E) applied to the electrochemical
      interface and deposition time. Film formation takes place at a noticeable rate at
      E = -1.0 V (vs SCE). High-resolution STM images at the early stages of growth
      show small particles, 5-8 nm in size and 0.3-0.4 nm in height, forming ordered
      arrays that follow closely the Au(111) topography. The size of the melanin
      particles increases as the film thickness increases, reaching 150 nm for deposits
      grown for 16 h. The deposited films are electrochemically active, showing well
      defined redox couples preceding the hydrogen evolution reaction.

PMID- 15952844
TI  - Effect of alpha-lactalbumin on the phase behavior of AOT-brine-isooctane
      mixtures: role of charge interactions.
AB  - We have found that both electrostatic and hydrophobic interactions are involved
      in the ability of the protein alpha-lactalbumin (alpha-LA) to affect the self
      assembly of the anionic surfactant sodium bis(ethylhexyl) sulfosuccinate (AOT,
      3.5 wt %) in equivolume mixtures of organic and aqueous solutions. The
      composition and size of AOT phase structures that form in the presence of 0.35 wt
      % protein were evaluated as a function of pH and ionic strength. In the absence
      of protein, AOT forms water-in-oil microemulsion droplets for all pH and salt
      concentrations studied here. The presence of the protein in the water-in-oil
      microemulsion phase boosts water solubilization and droplet size, as the
      spontaneous curvature of the surfactant interface becomes less negative.
      Aggregates of protein, surfactant, and oil also form in the water-continuous
      phase. The size and composition of structures in both phases can be tuned in the
      presence of protein by varying the pH and ionic strength. alpha-LA induces the
      appearance of an anisotropic surfactant phase at pH <5.8. At intermediate salt
      concentrations, a third isotropic, viscous aqueous phase appears that contains 55
      60% of the protein, 10-14% of the surfactant, and significant amounts of oil.
      Circular dichroism and fluorescence spectroscopy indicate that the protein
      contains enhanced alpha-helical secondary structure when self-assembling with
      surfactant, and has a loosened tertiary structure. The protein does not interact
      with the surfactant as an unfolded random coil. Although the conformation of
      alpha-LA in aqueous salt solutions is known to depend on pH, when self-assembling
      with AOT the protein adopts a structure whose features are quite pH insensitive,
      and likely reflect an intrinsic interaction with the interface.

PMID- 15952845
TI  - Fungal biomass with grafted poly(acrylic acid) for enhancement of Cu(II) and
      Cd(II) biosorption.
AB  - The biomass of Penicillium chrysogenum was modified by graft polymerization of
      acrylic acid (AAc) on the surface of ozone-pretreated biomass. The sorption
      capacity for copper and cadmium increased significantly as a large number of
      carboxyl groups were present on the biomass surface, especially when the
      carboxylic acid group was converted to carboxylate ions using NaOH. When modeled
      using the Langmuir isotherm, the sorption capacities were 1.70 and 1.87 mmol g(
      1) for copper and cadmium, respectively. The loaded biosorbent was regenerated
      using HCl solution and used repeatedly over five cycles with little loss of
      uptake capacity beyond the second cycle. The sorption of the two metals was time
      dependent, and the kinetics fitted the pseudo-second-order equation well. The
      Freundlich, Langmuir, Temkin, and Dubinin-Redushkevich isotherms were used to
      model the metal sorption isotherms, and the thermodynamic parameters calculated
      show that the sorption was spontaneous and endothermic under the condition
      applied and that the biomass has similar sorption affinities for the two metals.
      Fourier transform infrared and X-ray photoelectron spectroscopy reveal that
      carboxyl, amide, and hydroxyl groups on the biomass surface were involved in the
      sorption of copper and cadmium and ion exchange and complexation dominated the
      sorption process.

PMID- 15952846
TI  - Gold nanoparticle formation during bromoaurate reduction by amino acids.
AB  - The synthesis and characterization of water-soluble dispersions of gold
      nanoparticles by the reduction of a potassium tetrabromoaurate precursor solution
      using the amino acids L-tyrosine, glycyl-L-tyrosine, and L-arginine using
      alkaline synthesis conditions are reported. The particle sizes determined by
      small-angle X-ray scattering (SAXS) and high-resolution transmission electron
      microscopy (HRTEM) measurements are found to be inversely proportional to the
      rate of particle formation, which was determined by time-resolved UV-visible
      spectrophotometry measurements, and vary very slowly at intermediate gold
      concentrations and rapidly at the extremes. Dispersions produced with a mixture
      of the two amino acids glycyl-L-tyrosine and L-tyrosine showed particle sizes and
      particle size distributions which were directly proportional to the ratio of the
      two L-amino acids, thus offering the possibility for control over the properties
      of the gold nanoparticle dispersions.

PMID- 15952847
TI  - Covalent immobilization of lysozyme on stainless steel. Interface spectroscopic
      characterization and measurement of enzymatic activity.
AB  - A new strategy aiming at the protection of metallic surfaces against the growth
      of biofilms is presented here. This work reports the grafting of primary amines
      by aminosilanization of oxidized stainless steel followed by chemical coupling of
      the glycosidase lysozyme from hen egg white using glutaraldehyde as
      homobifunctional cross-linking agent. Controlled characterization of a stainless
      steel surface by X-ray photoelectron spectroscopy and Fourier transform infrared
      reflection-absorption spectroscopy at each step enabled the mode of binding,
      coverage, and orientation of the grafted molecules to be addressed. As a result,
      the stainless steel samples covered with a covalently immobilized layer of
      lysozyme showed some lytic activity on a suspension of bacteria Micrococcus
      lysodeikticus.

PMID- 15952848
TI  - Real-time QCM-D immunoassay through oriented antibody immobilization using cross
      linked hydrogel biointerfaces.
AB  - This report presents the development of pre-cross-linked and in situ cross-linked
      polyethyleneimine-carboxymethylcellulose antibody immobilization platforms for
      real-time QCM-D immunoassay of sepsis-related biomarkers. These platforms differ
      significantly from recent trends in QCM-based assays, a rapidly expanding field
      given the affordability and sensitivity of the transduction system, by providing
      ultrafast biointerface deposition through cross-linking of polysaccharides. Using
      rhIL-1ra (17 kDa), a known sepsis biomarker, for development, various immunoassay
      modifications to increase sensitivity were investigated, including the use of
      Protein A, Protein G, and anti-IgG Fc specific antibody capture ligands for
      oriented antibody immobilization, higher-frequency QCM-D crystals, and
      amplification using secondary antibodies. The optimized assay employs Protein A
      oriented immobilization on pre-cross-linked polymer and secondary antibodies to
      achieve a detection limit of 25 ng/mL on 5 MHz crystals. Assay repeatability
      using the optimized chemistry is robust, with no loss in 100 ng/mL antigen
      detection over 20 cycles of the 10 min sandwich assay. Nonspecific adsorption of
      human serum albumin, as characterized by ToF-SIMS, is minimal and negligible for
      the pre-cross-linked and in situ cross-linked compositions, respectively.

PMID- 15952849
TI  - High-resolution 2D 1H-15N NMR characterization of persistent structural
      alterations of proteins induced by interactions with silica nanoparticles.
AB  - The binding of protein to solid surfaces often induces changes in the structure,
      and to investigate these matters we have selected two different protein
      nanoparticle systems. The first system concerns the enzyme human carbonic
      anhydrase II which binds essentially irreversibly to the nanoparticles, and the
      second system concerns human carbonic anhydrase I which alternate between the
      adsorbed and free state upon interaction with nanoparticles. Application of the
      TROSY pulse sequence has allowed high-resolution NMR analysis for both of the
      protein-nanoparticle systems. For HCAII it was possible to observe spectra of
      protein when bound to the nanoparticles. The results indicated that HCAII
      undergoes large rearrangements, forming an ensemble of molten globule-like
      structures on the surface. The spectra from the HCAI-nanoparticle system are
      dominated by HCAI molecules in solution. A comparative analysis of variations in
      intensity from 97 amide resonances in a 1H-15N TROSY spectrum revealed the
      effects from interaction with nanoparticle on the protein structure at amino acid
      resolution.

PMID- 15952850
TI  - Adsorption of fibrinogen and lysozyme on silicon grafted with poly(2
      methacryloyloxyethyl phosphorylcholine) via surface-initiated atom transfer
      radical polymerization.
AB  - Surfaces based on grafted poly(2-methacryloyloxyethyl phosphorylcholine)
      (poly(MPC)) "brushes" with a constant graft density of 0.39 chain/nm2 and chain
      length from 5 to 200 monomer units were prepared by surface-initiated atom
      transfer radical polymerization (ATRP) on silicon wafers. The chain length and
      layer thickness of the poly(MPC) grafts were varied via the ratio of MPC to
      sacrificial initiator. The surfaces were characterized by water contact angle,
      XPS, and AFM. The effect of poly(MPC) chain length on fibrinogen and lysozyme
      adsorption was studied in TBS buffer at pH 7.4. The adsorption of both proteins
      on the poly(MPC)-grafted surfaces was greatly reduced compared to the unmodified
      silicon. Adsorption decreased with increasing chain length of the poly(MPC)
      grafts. Grafts of chain length 200 (MW 59 000) gave adsorption levels of 7 and 2
      ng/cm2, respectively, for fibrinogen and lysozyme at 1 mg/mL protein
      concentration, corresponding to reductions of greater than 98% compared to the
      unmodified silicon. Adsorption experiments using mixtures of the two proteins
      showed that the suppression of protein adsorption on the poly(MPC)-grafted
      surfaces was not strongly dependent on protein size or charge.

PMID- 15952851
TI  - Solvent-controlled organization of self-assembled polymeric monolayers on gold:
      an easy approach for the construction of protein resistant surfaces.
AB  - Protein resistant surfaces based on poly(ethylene glycol) (PEG) coatings are
      extensively applied in the fields of biosensors, tissue engineering, fundamental
      cell-surface interaction research, and drug delivery systems. The structural
      organization of the PEG film on the surface has a significant effect on the
      performance of the film to resist protein adsorption. In this paper, we report an
      approach using solvent to control the organization of the polymeric monolayer on
      gold. A water soluble copolymer with grafted PEG side chains and alkyl disulfide
      side chains was synthesized. A polymeric monolayer was fabricated on a gold
      surface from different solutions (water- and toluene-based) of the copolymer. The
      organization of the polymeric monolayers was characterized by means of
      ellipsometry, cyclic voltammetry, contact angle, X-ray photoelectron
      spectroscopy, and atomic force microscopy. It was proven that the structural
      organization of the polymeric monolayer on a gold surface could be controlled by
      the solvent. A polymeric monolayer with PEG enriched at the outer level is
      obtained when water is used as the solvent. Various types of proteins, including
      fibrinogen, albumin, and normal human serum, were used to test the protein
      resistance of the gold surfaces modified by the polymeric monolayers. The
      polymeric monolayer formed from a water solution of the copolymer showed
      excellent protein resistance. In addition, by using water as the solvent,
      patterning of the polymeric monolayer could easily be achieved through a
      combination of lift-off and self-assembly. We believe that the approach reported
      here provides an easy, fast, and efficient way to fabricate a robust protein
      resistant surface.

PMID- 15952853
TI  - A green chemical approach to the synthesis of tellurium nanowires.
AB  - Starch, an economical and safe carbohydrate, has been found to be not only an
      effective reducing agent but also a new morphology-directing agent for the
      synthesis of tellurium nanowires using commercial H2TeO4 precursor. The obtained
      tellurium nanowires are of single-crystal in nature, with an average diameter of
      approximately 25 nm and length up to 10 microm. A possible synthetic mechanism
      involves the chain-shaped bioorganic molecule acting as a template for the one
      dimensional growth of inorganic tellurium. The effects of different chain-shaped
      structures and concentrations of biomolecules on the nanowire morphology have
      been investigated and different one-dimensional structures, including thick rods,
      short nanowires, bunched nanowires, and assembled spikelet structures, have been
      fabricated. These experimental results have been found to be useful in
      substantiating the proposed synthetic mechanism.

PMID- 15952852
TI  - Interaction of poly-L-arginine with dihexadecyl phosphate/phosphatidylcholine
      liposomes.
AB  - In the present study, mixed liposomes of dihexadecyl phosphate sodium
      salt:phosphatidylcholine:cholesterol at a 1:19:9.5 molar ratio were allowed to
      interact with poly-L-arginine at temperatures below and above the main phase
      transition of the liposomal membrane. The interaction led to the formation of
      aggregates, which gradually increased in size and eventually precipitated. It
      was, however, possible, during the initial stage of the experiments, when the
      ratio of guanidinium group relative to phosphate was smaller than ca. 40%, to
      determine their size and charge and observe their morphology in aqueous
      dispersion. Fluorescence experiments established that the liposomes are not
      ruptured during their interaction with poly-L-arginine. Instead, they are
      attached at the polypeptide chain through the guanidinium-phosphate complementary
      pair. Fluorescence quenching experiments indicated that the poly-L-arginine chain
      is accessible for interaction with iodides dissolved in the aqueous phase when
      the temperature of the liposomal dispersion is below the main lipid phase
      transition. It is, however, partitioned in the interior of the membrane at
      temperatures exceeding this main lipid phase transition.

PMID- 15952854
TI  - Controlled clustering and enhanced stability of polymer-coated magnetic
      nanoparticles.
AB  - The clustering and stability of magnetic nanoparticles coated with random
      copolymers of acrylic acid, styrenesulfonic acid, and vinylsulfonic acid has been
      studied. Clusters larger than 50 nm are formed when the coatings are made using
      too low or too high molecular weight polymers or using insufficient amounts of
      polymer. Low-molecular-weight polymers result in thin coatings that do not
      sufficiently screen van der Waals attractive forces, while high-molecular-weight
      polymers bridge between particles, and insufficient polymer results in bare
      patches on the magnetite surface. The stability of the resulting clusters is
      poor, but when an insufficient polymer is used as primary coating, and a
      secondary polymer is added to coat remaining bare magnetite, the clusters are
      stable in high salt concentrations (>5 M NaCl), while retaining the necessary
      cluster size for efficient magnetic recovery. The magnetite cores were
      characterized by TEM and vibrating sample magnetometry, while the clusters were
      characterized by dynamic light scattering. The clustering and stability are
      interpreted in terms of the particle-particle interaction forces, and the optimal
      polymer size can be predicted well on the basis of these forces and the solution
      structure and hydrophobicity of the polymer. The size of aggregates formed by
      limited polymer can be predicted with a diffusion-limited colloidal aggregation
      model modified with a sticking probability based on fractional coating of the
      magnetite cores.

PMID- 15952855
TI  - Ag@C core/shell structured nanoparticles: controlled synthesis, characterization,
      and assembly.
AB  - Silver nanoparticles with tunable sizes were encapsulated in a carbonaceous shell
      through a green wet chemical route-the catalyzed dehydration of glucose under
      hydrothermal condition. In this one-pot synthesis, glucose was used as the
      reducing agent to react with Ag+ or Ag(NH3)2+, and it also served as the source
      of carbonaceous shells. The effects of hydrothermal temperature, time, and the
      concentrations of reagents on formation of the final nanostructures were
      systematically studied. The presence of competitive molecules poly(vinyl
      pyrrolidone) was found to be able to relieve the carbonization process, to
      incorporate themselves into carbonaceous shell, and to make the carbonaceous
      shell colorless. All these approaches provided diverse means to tailor the Ag@C
      nanostructures. By evaporation of the solvents gradually in a moist atmosphere,
      the monodispersed nanoparticles could self-assemble into arrays. Transmission
      electron microscopy, scanning electron microscopy, and UV-vis extinction spectra
      and surface-enhanced Raman spectra were used to characterize the core/shell
      nanostructures. These Ag@C core/shell nanoparticles have hydrophilic, organic
      group-loaded surfaces and characteristic optical properties, which indicated
      their promising applications in optical nanodevices and biochemistry.

PMID- 15952856
TI  - Amperometric immunosensor for direct detection based upon functional lipid
      vesicles immobilized on nanowell array electrode.
AB  - An original electrochemical immunosensor has now been developed that is based
      upon the spontaneous immobilization of biotinylated, functional lipid vesicles
      (FLVs) on a polymeric resist layer. An electrode was fabricated utilizing a form
      of electron-beam (e-beam) that has been used to fabricate 200 nm (nanoscale)
      wells in the resist layer covering of the gold electrode. The stability of
      adhered FLVs upon the nanowell (NW) electrode was observed by atomic force
      microscopy (AFM). From these observations, we were able to determine that the
      assembled FLVs primarily adhered as individual molecules, that is, without the
      aggregation or fusion noted in earlier designs. Additionally, these immobilized
      FLVs demonstrated clearly defined redox activity in electrochemical measurements.
      Streptavidin, biotinylated capture antibody, and target proteins were
      consequently injected in order to set up the immunoassay environment.
      Electrochemical immunoassay experimentation was performed on the NW array
      electrode with model proteins, such as human serum albumin (HSA) and carbonic
      anhydrase from bovine (CAB). We observed a notable current decrease, following
      the redox path, interrupted by the target HSA, indicating the binding of the
      capture antibody with the target antigen. On the basis of these results, we
      propose a new type of immunosensor incorporating this mechanism of spontaneous
      immobilization of FLVs.

PMID- 15952857
TI  - Use of linear polymers to control the preparation of luminescent organic
      microcrystals.
AB  - Microcrystals of an organic fluorescent dye, 4-octylamino-7-nitrobenz-2-oxa-1,3
      diazole, were generated using the reprecipitation method, which is a solvent
      exchange process. In the presence of polymers, namely, poly(acrylic acid),
      molecular weight 5100 g mol(-1) and 15 000 g mol(-1), and poly(acrylic acid-co
      maleic acid), average molecular weight about 50 000 g mol(-1), used as their
      sodium salts, the reprecipitation process was strongly accelerated. The
      reprecipitation kinetics was monitored by UV/vis absorption spectroscopy and
      revealed a three-step mechanism, each step being influenced by the polymer. The
      size and shape of the microcrystals were analyzed by fluorescence microscopy. The
      microcrystals obtained in the presence of polymers were smaller and more regular
      than those prepared in water alone and were not agglomerated. When the polymer
      was placed in the reprecipitation medium before introducing the dye solution, the
      microcrystals displayed a rectangular shape. When the polymer was introduced 20
      min after the beginning of the reprecipitation process, intricately structured
      flowerlike microcrystals were observed. Microanalysis revealed that the
      microcrystals contained noticeable amounts of polymer. The measurement of the
      surface electric zeta potential suggested that a proportion of the polymer was
      present at the microcrystal surface. This work gives a thorough insight into a
      field where trials have until now been performed in an empirical way. It opens
      new perspectives to produce low-cost organic microcrystals, potentially useful in
      optics or pharmaceutical sciences.

PMID- 15952858
TI  - Tight confinement of semiconductor quantum dots within zeolite by surface
      silylation.
AB  - Various MX (M = Cd, Zn, and Mn, X = S and Se) semiconductor quantum dots (QDs)
      were prepared in zeolite Y. While the QDs are readily expelled from zeolite
      interior upon exposure of the MX QD-incorporating zeolite Y ([MX]-Y) to the
      ambient atmosphere due to moisture adsorption, they remain tightly confined
      within zeolites even after exposure to the moist atmosphere for several weeks
      when the surfaces were silylated with various silylating agents. This methodology
      will facilitate the characterization of the zeolite-encapsulated QDs and the
      application of QD-incorporating zeolites.

PMID- 15952859
TI  - Polymerization of w/o microemulsions for the preparation of transparent SiO2/PMMA
      nanocomposites.
AB  - Reverse w/o microemulsions composed of methyl methacrylate (MMA) forming the oil
      phase, nonionic surfactants, and water are used for the synthesis of transparent
      SiO2/PMMA nanocomposites. An inorganic precursor, tetraethoxysilane (Si(OEt)(4),
      TEOS), is hydrolyzed in the reverse micelles containing aqueous ammonia. During
      the hydrolysis of TEOS, polymerization of the continuous MMA phase is initiated
      using AIBN (azobisisobutyronitrile), and after thermal polymerization at 333 K
      for 12 h, solid blocks of PMMA are obtained in which nanometer-sized silica
      particles are trapped in the solid polymer matrix. According to small-angle X-ray
      and dynamic light scattering experiments, the water droplets in MMA
      microemulsions are 12 nm (R(W) = 13) in diameter, whereas after polymerization of
      the microemulsion, the SiO2 particles in the transparent SiO2/PMMA composites are
      26 nm in diameter. Transmission electron micrographs demonstrate a low degree of
      agglomeration in the composites. In comparison with materials generated from
      micelle-free solutions, the particle size distribution is narrow. The reverse
      micelle-mediated approach produces composites of high transparency comparable
      with that of pure PMMA.

PMID- 15952860
TI  - Efficient surface grafting of luminescent silicon quantum dots by photoinitiated
      hydrosilylation.
AB  - We suggest a method for efficient (high-coverage) grafting of organic molecules
      onto photoluminescent silicon nanoparticles. High coverage grafting was enabled
      by use of a modified etching process that produces a hydrogen-terminated surface
      on the nanoparticles with very little residual oxygen and by carefully excluding
      oxygen during the grafting process. It had not previously been possible to
      produce such a clean H-terminated surface on free silicon nanoparticles or,
      subsequently, to produce grafted particles without significant surface oxygen.
      This allowed us to (1) prepare air-stable green-emitting silicon nanoparticles,
      (2) prepare stable dispersions of grafted silicon nanoparticles in a variety of
      organic solvents from which particles can readily be precipitated by addition of
      nonsolvent, dried, and redispersed, (3) separate these nanoparticles by size (and
      therefore emission color) using conventional chromatographic methods, (4) protect
      the particles from chemical attack and photoluminescence quenching, and (5)
      provide functional groups on the particle surface for further derivatization. We
      also show, using 1H NMR, that the photoinitiated hydrosilylation reaction does
      not specifically graft the terminal carbon atom to the surface but that
      attachment at both the first and second atom occurs.

PMID- 15952861
TI  - Gold nanoparticle/polymer nanocomposites: dispersion of nanoparticles as a
      function of capping agent molecular weight and grafting density.
AB  - The dispersion of polymer-covered gold nanoparticles in high molecular weight
      (MW) polymer matrixes is reported. Complete particle dispersion was achieved for
      PS125-Au in the polystyrene (PS) matrixes studied (up to and including Mn = 80
      000 g/mol). PS19-Au, on the other hand, exhibits complete dispersion in a low MW
      PS matrix (Mn = 2000 g/mol) but only partial dispersion in higher MW matrixes (up
      to 80 000 g/mol). Similarly, PEO45-Au is fully dispersed in a low MW
      poly(ethylene oxide) (PEO) matrix (Mn = 1000 g/mol) but only partially in a
      higher MW PEO matrix (Mn = 15 000 g/mol). Wetting of the polymer-Au brushes by
      the polymer matrix is associated with dispersibility. Theory predicts that, for
      dense polymer brushes, wetting is achieved when the MW of the polymer brush
      equals (and is greater than) that of the polymer matrix. The observed partial
      dispersion of the PS19-Au and PEO45-Au nanoparticles in matrixes whose MW is
      greater than the brush MW is attributable to the existence of a high volume
      fraction of voids within the brush. These voids arise from the unique geometry of
      the nanoparticle surface arising from the juxtaposed facets of the gold
      nanoparticle. PS125-Au brushes are wetted by PS matrixes whose degree of
      polymerization is larger than 125, probably because of their lower grafting
      density on the gold core or the high fraction of void volumes caused by the
      facets on the gold cores. Dispersion thus occurs when the matrix MW is greater
      than that of the brush.

PMID- 15952862
TI  - Electron beam irradiation of poly(vinyl methyl ether) films: 1. Synthesis and
      film topography.
AB  - Temperature-sensitive hydrogel layers on silicon (Si) substrates were synthesized
      by electron beam irradiation of spin-coated poly(vinyl methyl ether) (PVME)
      films. The influences of the used solvent, the polymer concentration, and the
      spinning velocity on the homogeneity and the thickness of the PVME film were
      investigated. In the range of concentration c(p) = 1-15 wt% PVME in ethanol
      solution, homogeneous films with a thickness between d = 50 nm and 1.7 mum were
      obtained. The films were cross-linked by electron beam irradiation under inert
      atmosphere and analyzed by sol-gel-analysis. The results were compared with
      bulkgels formed by electron beam irradiation of PVME in the dry state. The film
      topography was analyzed by high-resolution field emission scanning electron
      microscopy and atomic force microscopy. An islandlike structure in the dry,
      swollen, and shrunken state of the hydrogel films was observed.

PMID- 15952863
TI  - In situ infrared spectroscopy study on imidization reaction and imidization
      induced refractive index and thickness variations in microscale thin films of a
      poly(amic ester).
AB  - Poly(amic ester) (PAE) is a soluble precursor of polyimide that has attracted
      interest from both the microelectronic and the flat-panel display industries
      because of its several important advantages, including excellent solubility, high
      hydrolytic stability, and solvent-free film formation, over the polyimide
      precursor, poly(amic acid), for which monomer-polymer equilibration always occurs
      in solution due to its carboxylic acid groups. In this study, poly(3,4'
      oxydiphenylene pyromellitamic diethyl ester) (PMDA-3,4'-ODA PAE) was chosen as a
      PAE precursor, and its thermal imidization behavior in microscale thin films was
      investigated quantitatively for the first time using time-resolved infrared (IR)
      spectroscopy. In addition, the variations of the film refractive index and
      thickness with temperature and time were determined in detail from the time
      resolved IR spectra and are fully interpreted in this paper by considering the
      imidization kinetics of the precursor.

PMID- 15952864
TI  - Layer-by-layer fabrication and characterization of DNA-wrapped single-walled
      carbon nanotube particles.
AB  - Carbon nanotubes have been proposed as support materials for numerous
      applications, including the development of DNA sensors. One of the challenges is
      the immobilization of DNA or other biological molecules on the sidewall of carbon
      nanotubes. This paper introduces a new fabrication of DNA-carbon nanotubes
      particles using the layer-by-layer (LBL) technique on single-walled carbon
      nanotubes (SWCNTs). Poly(diallyldimethylammonium) (PDDA), a positively charged
      polyelectrolyte, and DNA as a negatively charged counterpart macromolecule are
      alternatively deposited on the water-soluble oxidized SWCNTs. Pure
      DNA/PDDA/SWCNTs particles can be prepared and separated by simple
      unltracentrifugation. The characterization of DNA/PDDA/SWCNTs particles was
      carried out by scanning electron microscopy (SEM), transmission electron
      microscopy (TEM), UV-visible spectroscopy, Raman spectroscopy, and
      thermogravimetric analysis (TGA). An electrode modified by the DNA/PDDA/SWCNTs
      particles shows a dramatic change of the electrochemical signal in solutions of
      tris(2,2'-bipyridyl)ruthenium(II) ((Ru(bpy)(3)2+) as a reporting redox probe. A
      preliminary application of the DNA-modified carbon nanotubes in the development
      of DNA sensors used in the investigation of DNA damage by nitric oxide is
      presented.

PMID- 15952865
TI  - Microemulsion-mediated solvothermal synthesis of SrCO3 nanostructures.
AB  - The controlled synthesis of SrCO3 nanostructures with different morphologies,
      such as rodlike, whiskerlike, ellipsoidlike, and spherelike, were successfully
      achieved by the cationic surfactant-CTAB-microemulsion-mediated solvothermal
      method. Various comparison experiments showed that fundamental experimental
      parameters, such as the molar ratio of H2O to CTAB and the concentration of
      reactants, played important roles in the morphological control of SrCO3
      nanostructures. A lower molar ratio of H2O to CTAB favors rodlike products,
      whereas a higher molar ratio generally leads to the formation of spherical
      products. A rational mechanism based on fusion, aggregate, and coalescence of
      microemulsion droplets is proposed for the selective formation of various
      morphologies. X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), selected area electron diffraction (SAED), and field-emission scanning
      electron microscope (FE-SEM) were used to characterize the products.

PMID- 15952866
TI  - Numerical analysis of electroosmotic flow in dense regular and random arrays of
      impermeable, nonconducting spheres.
AB  - We present a numerical scheme for analyzing steady-state isothermal
      electroosmotic flow (EOF) in three-dimensional random porous media, involving
      solution of the coupled Poisson, Nernst-Planck, and Navier-Stokes equations.
      While traditional finite-difference methods were used to resolve the Poisson
      Nernst-Planck problem, the (electro)hydrodynamics has been addressed with high
      efficiency using the lattice-Boltzmann method. The developed model allows
      simulation of electrokinetic transport under most general conditions, including
      arbitrary value and distribution of electrokinetic potential at the solid-liquid
      interface, electrolyte composition, and pore space morphology. The approach
      provides quantitative information on a spatial distribution of simulated
      velocities. This feature was utilized to characterize EOF fields in regular and
      random, confined and bulk packings of hard (i.e., impermeable, nonconducting)
      spheres. Important aspects of pore space morphology (sphere size distribution),
      surface heterogeneity (mismatch in electrokinetic potentials at confining wall
      and sphere surface), and fluid phase properties (electrical double layer
      thickness) were investigated with respect to their influence on the EOF dynamics
      over microscopic and macroscopic spatial domains. Most important is the
      observation of a generally nonuniform pore-level EOF velocity profile in the
      sphere packings (even in the thin double layer limit) which is caused by pore
      space morphology and which is in contrast to the pluglike velocity distribution
      in a single, straight capillary under the same conditions.

PMID- 15952867
TI  - Molecular dynamics simulations of layer-by-layer assembly of polyelectrolytes at
      charged surfaces: effects of chain degree of polymerization and fraction of
      charged monomers.
AB  - We performed molecular dynamics simulations of the electrostatic assembly of
      multilayers of flexible polyelectrolytes at a charged surface. The multilayer
      build-up was achieved through sequential adsorption of oppositely charged
      polymers in a layer-by-layer fashion from dilute polyelectrolyte solutions. The
      steady-state multilayer growth proceeds through a charge reversal of the adsorbed
      polymeric film which leads to a linear increase in the polymer surface coverage
      after completion of the first few deposition steps. Moreover, substantial
      intermixing between chains adsorbed during different deposition steps is
      observed. This intermixing is consistent with the observed requirement for
      several deposition steps to transpire for completion of a single layer. However,
      despite chain intermixing, there are almost perfect periodic oscillations of the
      density difference between monomers belonging to positively and negatively
      charged macromolecules in the adsorbed film. Weakly charged chains show higher
      polymer surface coverage than strongly charged ones.

PMID- 15952868
TI  - Applying proteomics in clinical trials: assessing the potential and practical
      limitations in ovarian cancer.
AB  - Ovarian cancer is the leading cause of death from gynecologic malignancies among
      American women and the fourth most frequent cause of death from cancer in women
      in Europe and the US. Despite appropriate surgical and chemotherapeutic
      intervention, the 5-year survival in patients with metastatic cancer remains
      poor. Currently available screening methods, including CA125, additional
      biomarkers, and transvaginal ultrasound lack the necessary sensitivity and
      specificity to provide accurate and cost-efficient screening for the general
      population or the ability to assess who will benefit most from each treatment.
      These limitations have prompted the study of proteomic technology and its
      application in ovarian cancer diagnostics. Proteomics is the study of molecules
      in the functional protein pathways of normal or diseased states. Clinical trials
      are currently being conducted to assess the sensitivity and specificity of serum
      proteomic patterns and additional clinical trials are designed to evaluate the
      effects of molecularly targeted agents on protein signaling pathways in human
      subjects. Overcoming both scientific and practical limitations will lead to
      increased knowledge of deranged protein networks in cancer cells. Clinical trials
      in proteomics may result in improved early detection, better monitoring, new
      drugs and molecularly targeted therapeutics, and individualized therapies.

PMID- 15952869
TI  - Genetics and epigenetics in major psychiatric disorders: dilemmas, achievements,
      applications, and future scope.
AB  - No specific gene has been identified for any major psychiatric disorder,
      including schizophrenia, in spite of strong evidence supporting a genetic basis
      for these complex and devastating disorders. There are several likely reasons for
      this failure, ranging from poor study design with low statistical power to
      genetic mechanisms such as polygenic inheritance, epigenetic interactions, and
      pleiotropy. Most study designs currently in use are inadequate to uncover these
      mechanisms. However, to date, genetic studies have provided some valuable insight
      into the causes and potential therapies for psychiatric disorders. There is a
      growing body of evidence suggesting that the understanding of the genetic
      etiology of psychiatric illnesses, including schizophrenia, will be more
      successful with integrative approaches considering both genetic and epigenetic
      factors. For example, several genes including those encoding dopamine receptors
      (DRD2, DRD3, and DRD4), serotonin receptor 2A (HTR2A) and catechol-O
      methyltransferase (COMT) have been implicated in the etiology of schizophrenia
      and related disorders through meta-analyses and large, multicenter studies. There
      is also growing evidence for the role of DRD1, NMDA receptor genes (GRIN1,
      GRIN2A, GRIN2B), brain-derived neurotrophic factor (BDNF), and dopamine
      transporter (SLC6A3) in both schizophrenia and bipolar disorder. Recent studies
      have indicated that epigenetic modification of reelin (RELN), BDNF, and the DRD2
      promoters confer susceptibility to clinical psychiatric conditions. Pharmacologic
      therapy of psychiatric disorders will likely be more effective once the molecular
      pathogenesis is known. For example, the hypoactive alleles of DRD2 and the
      hyperactive alleles of COMT, which degrade the dopamine in the synaptic cleft,
      are associated with schizophrenia. It is likely that insufficient dopaminergic
      transmission in the frontal lobe plays a role in the development of negative
      symptoms associated with this disorder. Antipsychotic therapies with a partial
      dopamine D2 receptor agonist effect may be a plausible alternative to current
      therapies, and would be effective in symptom reduction in psychotic individuals.
      It is also possible that therapies employing dopamine D1/D2 receptor agonists or
      COMT inhibitors will be beneficial for patients with negative symptoms in
      schizophrenia and bipolar disorder. The complex etiology of schizophrenia, and
      other psychiatric disorders, warrants the consideration of both genetic and
      epigenetic systems and the careful design of experiments to illumine the genetic
      mechanisms conferring liability for these disorders and the benefit of existing
      and new therapies.

PMID- 15952870
TI  - Preclinical drug safety analysis by chemogenomic profiling in the liver.
AB  - The economic hurdles of drug development and the emergence of genomic
      technologies such as chemogenomics are combining to shift the existing paradigms
      in preclinical drug development. Today, the information gleaned from high content
      molecular data has begun to augment traditional approaches to the assessment of
      drug safety. The optimal approach is a hybrid strategy employing chemogenomic
      data and gene expression-based biomarkers of drug efficacy and toxicity to
      supplement low content and insensitive methods for risk assessment and
      mechanistic evaluation of drug candidates. Large reference databases of
      chemogenomic data are essential to the derivation and validation of accurate and
      predictive gene expression biomarkers. An example of the development of a
      predictive biomarker for hepatic bile duct hyperplasia is described herein. As
      gene expression technologies improve, biomarkers will achieve higher throughput,
      and become more cost effective and increasingly accurate. This will elevate the
      value of chemogenomics in drug development, shift attrition to earlier in the
      process, and reduce the overall cost of drug development. Over the past 2 to 3
      years, the transition of chemogenomics from a research tool to a decision-making
      tool has begun and regulatory agencies are anxiously awaiting implementation of
      this technology to make faster and more informed evaluations of potential drugs.

PMID- 15952871
TI  - Oncogenes as novel targets for cancer therapy (part I): growth factors and
      protein tyrosine kinases.
AB  - In the past 10 years, progress made in cancer biology, genetics, and
      biotechnology has led to a major transition in cancer drug design and
      development. There has been a change from an emphasis on non-specific, cytotoxic
      agents to specific, molecular-based therapeutics. Mechanism-based therapy is
      designed to act on cellular and molecular targets that are causally involved in
      the formation, growth, and progression of human cancers. These agents, which may
      have greater selectivity for cancer versus normal cells, and which may produce
      better anti-tumor efficacy and lower host toxicity, can be small molecules,
      natural or engineered peptides, proteins, antibodies, or synthetic nucleic acids
      (e.g. antisense oligonucleotides, ribozymes, and siRNAs). Novel targets are
      identified and validated by state-of-the-art approaches, including high
      throughput screening, combinatorial chemistry, and gene expression arrays, which
      increase the speed and efficiency of drug discovery and development. Examples of
      oncogene-based, molecular therapeutics that show promising clinical activity
      include trastuzumab (Herceptin), imatinib (Gleevec), and gefitinib (Iressa).
      However, the full potential of oncogenes as novel targets for cancer therapy has
      not been realized and many challenges remain, from the validation of novel
      targets, to the design of specific agents, to the evaluation of these agents in
      both preclinical and clinical settings. In maximizing the benefits of molecular
      therapeutics in monotherapy or combination therapy of cancer, it is necessary to
      have an understanding of the underlying molecular abnormalities and mechanisms
      involved. This is the first part of a four-part review in which we discuss
      progress made in the last decade as it relates to the discovery of novel
      oncogenes and signal transduction pathways, in the context of their potential as
      targets for cancer therapy. This part delineates the latest discoveries about the
      potential use of growth factors and protein tyrosine kinases as targets for
      therapy. Later parts focus on intermediate signaling pathways, transcription
      factors, and proteins involved in cell cycle, DNA damage, and apoptotic pathways.

PMID- 15952872
TI  - CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients:
      data from the DEBATE Study.
AB  - OBJECTIVE: The aim of this study was to address the presently controversial
      question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with
      hypertension. METHOD: We studied 373 elderly (age > or =75 years) Finnish
      (Caucasian) patients from the ongoing DEBATE (Drugs and Evidence Based Medicine
      in the Elderly) trial. The patients were classified into those with a history of
      hypertension (n = 229) and those without a history of hypertension (n = 144) on
      the basis of a detailed questionnaire on each patient's medical history and an
      interview. The patients were genotyped for the CYP3A5 6986A/G single nucleotide
      polymorphism (SNP) [CYP3A5*1/*3 alleles]. RESULTS: The proportion of individuals
      with the CYP3A5*1/*3 genotype, i.e. CYP3A5 expressors, was significantly higher
      among patients with a diagnosis of hypertension than among patients without
      (18.3% vs 9.0%, p = 0.016). The corresponding odds ratio was 2.26 (95% CI 1.17,
      4.38). The allele and genotype frequencies for the two control SNPs, ABCB1 (MDR1)
      3435C/T and SLCO1B1 521T/C, did not differ between the two groups. CONCLUSION:
      This work lends support to the theory that the polymorphic CYP3A5 enzyme may be
      involved in regulation of blood pressure. The possible role of CYP3A5 as a
      genetic contributor to hypertension susceptibility warrants further study.

PMID- 15952873
TI  - Comparison of linear weighting schemes for perfect match and mismatch gene
      expression levels from microarray data.
AB  - BACKGROUND: Data analytic approaches to Affymetrix microarray data include: (a) a
      covariate model, in which the observed signal is some estimated linear function
      of perfect match (PM) and mismatch (MM) signals; (b) a difference model [PM-MM];
      and (c) a PM-only model, in which MM data is not utilized. METHODS: By
      decomposing the correlations among the variables in the statistical model and
      making certain assumptions, we theoretically derive the statistical model that
      reflects the actual gene expression level under a variety of conditions expected
      in microarray data. RESULTS AND CONCLUSION: When modeling non-systematic
      variation, the covariate model provides maximum flexibility and often reflects
      the actual gene expression levels better than the difference model. However, the
      PM-only model demonstrates superior power in an overwhelming majority of
      realistic situations, which provides theoretical support for the current trend to
      employ PM-only models in microarray data analyzes.

PMID- 15952874
TI  - A tool for analyzing mate pairs in assemblies (TAMPA).
AB  - The current generation of genome assembly programs uses distance and orientation
      relationships of paired end reads of clones (mate pairs) to order and orient
      contigs. Mate pair data can also be used to evaluate and compare assemblies after
      the fact. Earlier work employed a simple heuristic to detect assembly problems by
      scanning across an assembly to locate peak concentrations of unsatisfied mate
      pairs. TAMPA is a novel, computational geometry-based approach to detecting
      assembly breakpoints by exploiting constraints that mate pairs impose on each
      other. The method can be used to improve assemblies and determine which of two
      assemblies is correct in the case of sequence disagreement. Results from several
      human genome assemblies are presented.

PMID- 15952875
TI  - Multiplexing schemes for generic SNP genotyping assays.
AB  - Association studies in populations relate genomic variation among individuals
      with medical condition. Key to these studies is the development of efficient and
      affordable genotyping techniques. Generic genotyping assays are independent of
      the target SNPs and offer great flexibility in the genotyping process. Efficient
      use of such assays calls for identifying sets of SNPs that can be interrogated in
      parallel under constraints imposed by the genotyping technology. In this paper,
      we study problems arising in the design of genotyping experiments using generic
      assays. Our problem formulation deals with two main factors that affect the
      genotyping cost: the number of assays used and the number of PCR reactions
      required for sample preparation. We prove that the resulting computational
      problems are hard, but provide approximate and heuristic solutions to these
      problems. Our algorithmic approach is based on recasting the multiplexing
      problems as partitioning and packing problems on a bipartite graph. We tested our
      algorithmic approaches on an extensive collection of synthetic data and on data
      that was simulated using real SNP sequences. Our results show that the algorithms
      achieve near-optimal designs in many cases and demonstrate the applicability of
      generic assays to SNP genotyping.

PMID- 15952876
TI  - Survival trees for analyzing clinical outcome in lung adenocarcinomas based on
      gene expression profiles: identification of neogenin and diacylglycerol kinase
      alpha expression as critical factors.
AB  - We present survival trees as an exploratory tool for revealing new insights into
      gene expression profiles in combination with clinical patient data. Survival
      trees partition the patient data studied into groups with similar survival
      outcomes and identify characteristic genetic profiles within these groups. We
      demonstrate the application of survival trees in a study involving the expression
      profiles of 3,588 genes in 211 lung adenocarcinoma patients. The survival tree
      identified a group of early-stage cancer patients with relatively low survival
      rates and another group of advanced-stage patients with remarkably good survival
      outcome. For both groups, the tree identified characteristic expression profiles
      of genes that might play a role in cancerogenesis and disease progression,
      notably the genes for the netrin receptor neogenin and the Ras/Rho kinase
      modulator diacylglycerol kinase alpha.

PMID- 15952877
TI  - Genome phylogeny based on short-range correlations in DNA sequences.
AB  - The surprising fact that global statistical properties computed on a genomewide
      scale may reveal species information has first been observed in studies of
      dinucleotide frequencies. Here we will look at the same phenomenon with a totally
      different statistical approach. We show that patterns in the short-range
      statistical correlations in DNA sequences serve as evolutionary fingerprints of
      eukaryotes. All chromosomes of a species display the same characteristic pattern,
      markedly different from those of other species. The chromosomes of a species are
      sorted onto the same branch of a phylogenetic tree due to this correlation
      pattern. The average correlation between nucleotides at a distance k is
      quantified in two independent ways: (i) by estimating it from a higher-order
      Markov process and (ii) by computing the mutual information function at a
      distance k. We show how the quality of phylogenetic reconstruction depends on the
      range of correlation strengths and on the length of the underlying sequence
      segment. This concept of the correlation pattern as a phylogenetic signature of
      eukaryote species combines two rather distant domains of research, namely
      phylogenetic analysis based on molecular observation and the study of the
      correlation structure of DNA sequences.

PMID- 15952878
TI  - Word sense disambiguation in the biomedical domain: an overview.
AB  - There is a trend towards automatic analysis of large amounts of literature in the
      biomedical domain. However, this can be effective only if the ambiguity in
      natural language is resolved. In this paper, the current state of research in
      word sense disambiguation (WSD) is reviewed. Several methods for WSD have already
      been proposed, but many systems have been tested only on evaluation sets of
      limited size. There are currently only very few applications of WSD in the
      biomedical domain. The current direction of research points towards statistically
      based algorithms that use existing curated data and can be applied to large sets
      of biomedical literature. There is a need for manually tagged evaluation sets to
      test WSD algorithms in the biomedical domain. WSD algorithms should preferably be
      able to take into account both known and unknown senses of a word. Without WSD,
      automatic metaanalysis of large corpora of text will be error prone.

PMID- 15952879
TI  - From protein synthesis to genetic insertion.
AB  - In 1946, (14)C-cyanide made its appearance as an offshoot of the Atomic Energy
      Program. Our colleague Robert Loftfield built it into (14)C-alanine by the
      Strecker synthesis, and a lusty program directed toward uncovering the unknown
      mechanism of protein synthesis grew out of this beginning. The necessity for an
      undiscovered series of steps and enzymes was soon evident. A cell free system was
      developed, and a succession of components necessary for this new pathway tumbled
      out. ATP dependence, amino acid activation, the ribosome as the site of
      polypeptide formation, discovery of tRNA as the translation molecule linking the
      gene and protein sequence, and GTP as the essential energy ingredient in peptide
      chain extension all appeared from our laboratory within the next decade. A little
      later the AP(4)N family, whose functions remain imperfectly defined, of
      intracellular molecules was discovered. Isolation of specific species of RNA
      became a high priority, and we sequenced a small segment of the 3' end of the
      Rous sarcoma virus, just inside the poly(A) tail, at the same time the Gilbert
      group at Harvard was sequencing the 5' end. The sequence identity and polarity of
      the two ends suggested a circular intermediate in replication and predicted
      correctly that a synthetic antisense oligonucleotide targeted against this
      sequence might be a specific inhibitor of replication. More recently, we have
      evolved a technique that appears to achieve a trinucleotide insertion into tissue
      culture cells bearing a specific Delta508 mRNA triplet deletion, resulting in
      phenotypic reversion in the tissue culture.

PMID- 15952880
TI  - The biochemistry of Parkinson's disease.
AB  - Several genes have been identified for monogenic disorders that variably resemble
      Parkinson's disease. Dominant mutations in the gene encoding alpha-synuclein
      enhance the propensity of this protein to aggregate. As a consequence, these
      patients have a widespread disease with protein inclusion bodies in several brain
      areas. In contrast, mutations in several recessive genes (parkin, DJ-1, and
      PINK1) produce neuronal cell loss but generally without protein aggregation
      pathology. Progress has been made in understanding some of the mechanisms of
      toxicity: Parkin is an E3 ubiquitin ligase and DJ-1 and PINK1 appear to protect
      against mitochondrial damage. However, we have not yet fully resolved how the
      recessive genes relate to alpha-synuclein, or whether they represent different
      ways to induce a similar phenotype.

PMID- 15952881
TI  - Applications of DNA microarrays in biology.
AB  - DNA microarrays have enabled biology researchers to conduct large-scale
      quantitative experiments. This capacity has produced qualitative changes in the
      breadth of hypotheses that can be explored. In what has become the dominant mode
      of use, changes in the transcription rate of nearly all the genes in a genome,
      taking place in a particular tissue or cell type, can be measured in disease
      states, during development, and in response to intentional experimental
      perturbations, such as gene disruptions and drug treatments. The response
      patterns have helped illuminate mechanisms of disease and identify disease
      subphenotypes, predict disease progression, assign function to previously
      unannotated genes, group genes into functional pathways, and predict activities
      of new compounds. Directed at the genome sequence itself, microarrays have been
      used to identify novel genes, binding sites of transcription factors, changes in
      DNA copy number, and variations from a baseline sequence, such as in emerging
      strains of pathogens or complex mutations in disease-causing human genes. They
      also serve as a general demultiplexing tool to sort spatially the sequence-tagged
      products of highly parallel reactions performed in solution. A brief review of
      microarray platform technology options, and of the process steps involved in
      complete experiment workflows, is included.

PMID- 15952882
TI  - Zona pellucida domain proteins.
AB  - Many eukaryotic proteins share a sequence designated as the zona pellucida (ZP)
      domain. This structural element, present in extracellular proteins from a wide
      variety of organisms, from nematodes to mammals, consists of approximately 260
      amino acids with eight conserved cysteine (Cys) residues and is located close to
      the C terminus of the polypeptide. ZP domain proteins are often glycosylated,
      modular structures consisting of multiple types of domains. Predictions can be
      made about some of the structural features of the ZP domain and ZP domain
      proteins. The functions of ZP domain proteins vary tremendously, from serving as
      structural components of egg coats, appendicularian mucous houses, and nematode
      dauer larvae, to serving as mechanotransducers in flies and receptors in mammals
      and nonmammals. Generally, ZP domain proteins are present in filaments and/or
      matrices, which is consistent with the role of the domain in protein
      polymerization. A general mechanism for assembly of ZP domain proteins has been
      presented. It is likely that the ZP domain plays a common role despite its
      presence in proteins of widely diverse functions.

PMID- 15952883
TI  - Proline hydroxylation and gene expression.
AB  - Hypoxia-inducible factor (HIF) is a master transcriptional regulator of hypoxia
      inducible genes and consists of a labile alpha subunit (such as HIF1alpha) and a
      stable beta subunit (such as HIF1beta or ARNT). In the presence of oxygen,
      HIFalpha family members are hydroxylated on one of two conserved prolyl residues
      by members of the egg-laying-defective nine (EGLN) family. Prolyl hydroxylation
      generates a binding site for a ubiquitin ligase complex containing the von Hippel
      Lindau (VHL) tumor suppressor protein, which results in HIFalpha destruction. In
      addition, the HIFalpha transcriptional activation function is modulated further
      by asparagine hydroxylation by FIH (factor-inhibiting HIF), which affects
      recruitment of the coactivators p300 and CBP. These findings provide new
      mechanistic insights into oxygen sensing by metazoans and are the first examples
      of protein hydroxylation being used in intracellular signaling. The existence of
      three human EGLN family members, as well as other putative hydroxylases, raises
      the possibility that this signal is used in other contexts by other proteins.

PMID- 15952884
TI  - Structural insights into translational fidelity.
AB  - The underlying basis for the accuracy of protein synthesis has been the subject
      of over four decades of investigation. Recent biochemical and structural data
      make it possible to understand at least in outline the structural basis for tRNA
      selection, in which codon recognition by cognate tRNA results in the hydrolysis
      of GTP by EF-Tu over 75 A away. The ribosome recognizes the geometry of codon
      anticodon base pairing at the first two positions but monitors the third, or
      wobble position, less stringently. Part of the additional binding energy of
      cognate tRNA is used to induce conformational changes in the ribosome that
      stabilize a transition state for GTP hydrolysis by EF-Tu and subsequently result
      in accelerated accommodation of tRNA into the peptidyl transferase center. The
      transition state for GTP hydrolysis is characterized, among other things, by a
      distorted tRNA. This picture explains a large body of data on the effect of
      antibiotics and mutations on translational fidelity. However, many fundamental
      questions remain, such as the mechanism of activation of GTP hydrolysis by EF-Tu,
      and the relationship between decoding and frameshifting.

PMID- 15952885
TI  - Origins of the genetic code: the escaped triplet theory.
AB  - There is very significant evidence that cognate codons and/or anticodons are
      unexpectedly frequent in RNA-binding sites for seven of eight biological amino
      acids that have been tested. This suggests that a substantial fraction of the
      genetic code has a stereochemical basis, the triplets having escaped from their
      original function in amino acid-binding sites to become modern codons and
      anticodons. We explicitly show that this stereochemical basis is consistent with
      subsequent optimization of the code to minimize the effect of coding mistakes on
      protein structure. These data also strengthen the argument for invention of the
      genetic code in an RNA world and for the RNA world itself.

PMID- 15952886
TI  - An abundance of RNA regulators.
AB  - The importance of small, noncoding RNAs that act as regulators of transcription,
      of RNA modification or stability, and of mRNA translation is becoming
      increasingly apparent. Here we discuss current knowledge of regulatory RNA
      function and review how the RNAs have been identified in a variety of organisms.
      Many of the regulatory RNAs act through base-pairing interactions with target
      RNAs. The base-pairing RNAs can be grouped into two general classes: those that
      are encoded on the opposite strand of their target RNAs such that they contain
      perfect complementarity with their targets, and those that are encoded at
      separate locations on the chromosome and have imperfect base-pairing potential
      with their targets. Other regulatory RNAs act by modifying protein activity, in
      some cases by mimicking the structures of other RNA or DNA molecules.

PMID- 15952887
TI  - Membrane-associated guanylate kinases regulate adhesion and plasticity at cell
      junctions.
AB  - Tissue development, differentiation, and physiology require specialized cellular
      adhesion and signal transduction at sites of cell-cell contact. Scaffolding
      proteins that tether adhesion molecules, receptors, and intracellular signaling
      enzymes organize macromolecular protein complexes at cellular junctions to
      integrate these functions. One family of such scaffolding proteins is the large
      group of membrane-associated guanylate kinases (MAGUKs). Genetic studies have
      highlighted critical roles for MAGUK proteins in the development and physiology
      of numerous tissues from a variety of metazoan organisms. Mutation of Drosophila
      discs large (dlg) disrupts epithelial septate junctions and causes overgrowth of
      imaginal discs. Similarly, mutation of lin-2, a related MAGUK in Caenorhabditis
      elegans, blocks vulval development, and mutation of the postsynaptic density
      protein PSD-95 impairs synaptic plasticity in mammalian brain. These diverse
      roles are explained by recent biochemical and structural analyses of MAGUKs,
      which demonstrate their capacity to assemble well--efined--yet adaptable--protein
      complexes at cellular junctions.

PMID- 15952888
TI  - Structure, function, and formation of biological iron-sulfur clusters.
AB  - Iron-sulfur [Fe-S] clusters are ubiquitous and evolutionary ancient prosthetic
      groups that are required to sustain fundamental life processes. Owing to their
      remarkable structural plasticity and versatile chemical/electronic features [Fe
      S] clusters participate in electron transfer, substrate binding/activation,
      iron/sulfur storage, regulation of gene expression, and enzyme activity.
      Formation of intracellular [Fe-S] clusters does not occur spontaneously but
      requires a complex biosynthetic machinery. Three different types of [Fe-S]
      cluster biosynthetic systems have been discovered, and all of them are
      mechanistically unified by the requirement for a cysteine desulfurase and the
      participation of an [Fe-S] cluster scaffolding protein. Important mechanistic
      questions related to [Fe-S] cluster biosynthesis involve the molecular details of
      how [Fe-S] clusters are assembled on scaffold proteins, how [Fe-S] clusters are
      transferred from scaffolds to target proteins, how various accessory proteins
      participate in [Fe-S] protein maturation, and how the biosynthetic process is
      regulated.

PMID- 15952889
TI  - Cellular DNA replicases: components and dynamics at the replication fork.
AB  - DNA replicases are multicomponent machines that have evolved clever strategies to
      perform their function. Although the structure of DNA is elegant in its
      simplicity, the job of duplicating it is far from simple. At the heart of the
      replicase machinery is a heteropentameric AAA+ clamp-loading machine that couples
      ATP hydrolysis to load circular clamp proteins onto DNA. The clamps encircle DNA
      and hold polymerases to the template for processive action. Clamp-loader and
      sliding clamp structures have been solved in both prokaryotic and eukaryotic
      systems. The heteropentameric clamp loaders are circular oligomers, reflecting
      the circular shape of their respective clamp substrates. Clamps and clamp loaders
      also function in other DNA metabolic processes, including repair, checkpoint
      mechanisms, and cell cycle progression. Twin polymerases and clamps coordinate
      their actions with a clamp loader and yet other proteins to form a replisome
      machine that advances the replication fork.

PMID- 15952890
TI  - Eukaryotic translesion synthesis DNA polymerases: specificity of structure and
      function.
AB  - This review focuses on eukaryotic translesion synthesis (TLS) DNA polymerases,
      and the emphasis is on Saccharomyces cerevisiae and human Y-family polymerases
      (Pols) eta, iota, kappa, and Rev1, as well as on Polzeta, which is a member of
      the B-family polymerases. The fidelity, mismatch extension ability, and lesion
      bypass efficiencies of these different polymerases are examined and evaluated in
      the context of their structures. One major conclusion is that, despite the
      overall similarity of basic structural features among the Y-family polymerases,
      there is a high degree of specificity in their lesion bypass properties. Some are
      able to bypass a particular DNA lesion, whereas others are efficient at only the
      insertion step or the extension step of lesion bypass. This functional divergence
      is related to the differences in their structures. Polzeta is a highly
      specialized polymerase specifically adapted for extending primer termini opposite
      from a diverse array of DNA lesions, and depending upon the DNA lesion, it
      contributes to lesion bypass in a mutagenic or in an error-free manner.
      Proliferating cell nuclear antigen (PCNA) provides the central scaffold to which
      TLS polymerases bind for access to the replication ensemble stalled at a lesion
      site, and Rad6-Rad18-dependent protein ubiquitination is important for polymerase
      exchange.

PMID- 15952891
TI  - NOD-LRR proteins: role in host-microbial interactions and inflammatory disease.
AB  - Nods are cytosolic proteins that contain a nucleotide-binding oligomerization
      domain (NOD). These proteins include key regulators of apoptosis and pathogen
      resistance in mammals and plants. A large number of Nods contain leucine-rich
      repeats (LRRs), hence referred to as NOD-LRR proteins. Genetic variation in
      several NOD-LRR proteins, including human Nod2, Cryopyrin, and CIITA, as well as
      mouse Naip5, is associated with inflammatory disease or increased susceptibility
      to microbial infections. Nod1, Nod2, Cryopyrin, and Ipaf have been implicated in
      protective immune responses against pathogens. Together with Toll-like receptors,
      Nod1 and Nod2 appear to play important roles in innate and acquired immunity as
      sensors of bacterial components. Specifically, Nod1 and Nod2 participate in the
      signaling events triggered by host recognition of specific motifs in bacterial
      peptidoglycan and, upon activation, induce the production of proinflammatory
      mediators. Naip5 is involved in host resistance to Legionella pneumophila through
      cell autonomous mechanisms, whereas CIITA plays a critical role in antigen
      presentation and development of antigen-specific T lymphocytes. Thus, NOD-LRR
      proteins appear to be involved in a diverse array of processes required for host
      immune reactions against pathogens.

PMID- 15952892
TI  - Regulation of protein function by glycosaminoglycans--as exemplified by
      chemokines.
AB  - Immune modulators such as cytokines and growth factors exert their biological
      activity through high-affinity interactions with cell-surface receptors, thereby
      activating specific signaling pathways. However, many of these molecules also
      participate in low-affinity interactions with another class of molecules,
      referred to as proteoglycans. Proteoglycans consist of a protein core to which
      glycosaminoglycan (GAG) chains are attached. The GAGs are long, linear, sulfated,
      and highly charged heterogeneous polysaccharides that are expressed throughout
      the body in different forms, depending on the developmental or pathological state
      of the organ/organism. They participate in many biological functions, including
      organogenesis and growth control, cell adhesion, signaling, inflammation,
      tumorigenesis, and interactions with pathogens. Recently, it was demonstrated
      that certain chemokines require interactions with GAGs for their in vivo
      function. The GAG interaction is thought to provide a mechanism for retaining
      chemokines on cell surfaces, facilitating the formation of chemokine gradients.
      These gradients serve as directional cues to guide the migration of the
      appropriate cells in the context of their inflammatory, developmental, and
      homeostatic functions. In this review, we discuss GAGs and their interaction with
      proteins, with a special emphasis on the chemokine system.

PMID- 15952893
TI  - Structure and function of fatty acid amide hydrolase.
AB  - Fatty acid amide hydrolase (FAAH) is a mammalian integral membrane enzyme that
      degrades the fatty acid amide family of endogenous signaling lipids, which
      includes the endogenous cannabinoid anandamide and the sleep-inducing substance
      oleamide. FAAH belongs to a large and diverse class of enzymes referred to as the
      amidase signature (AS) family. Investigations into the structure and function of
      FAAH, in combination with complementary studies of other AS enzymes, have
      engendered provocative molecular models to explain how this enzyme integrates
      into cell membranes and terminates fatty acid amide signaling in vivo. These
      studies, as well as their biological and therapeutic implications, are the
      subject of this review.

PMID- 15952894
TI  - Nontemplate-dependent polymerization processes: polyhydroxyalkanoate synthases as
      a paradigm.
AB  - This review focuses on nontemplate-dependent polymerases that use water-soluble
      substrates and convert them into water-insoluble polymers that form granules or
      inclusions within the cell. The initial part of the review summarizes briefly the
      current knowledge of polymer formation catalyzed by starch and glycogen
      synthases, polyphosphate kinase (a polymerase), cyanophycin synthetases, and
      rubber synthases. Specifically, our current understanding of their mechanisms of
      initiation, elongation (including granule formation), termination, remodeling,
      and polymer reutilization will be presented. General underlying principles that
      govern these types of polymerization reactions will be enumerated as a paradigm
      for all nontemplate-dependent polymerizations. The bulk of the review then
      focuses on polyhydroxyalkanoate (PHA) synthases that generate polyoxoesters.
      These enzymes are of interest as they generate biodegradable polymers. Our
      current knowledge of PHA production and utilization in vitro and in vivo as well
      as the contribution of many proteins to these processes will be reviewed.

PMID- 15952895
TI  - Eukaryotic cytosine methyltransferases.
AB  - Large-genome eukaryotes use heritable cytosine methylation to silence promoters,
      especially those associated with transposons and imprinted genes. Cytosine
      methylation does not reinforce or replace ancestral gene regulation pathways but
      instead endows methylated genomes with the ability to repress specific promoters
      in a manner that is buffered against changes in the internal and external
      environment. Recent studies have shown that the targeting of de novo methylation
      depends on multiple inputs; these include the interaction of repeated sequences,
      local states of histone lysine methylation, small RNAs and components of the RNAi
      pathway, and divergent and catalytically inert cytosine methyltransferase
      homologues that have acquired regulatory roles. There are multiple families of
      DNA (cytosine-5) methyltransferases in eukaryotes, and each family appears to be
      controlled by different regulatory inputs. Sequence-specific DNA-binding
      proteins, which regulate most aspects of gene expression, do not appear to be
      involved in the establishment or maintenance of genomic methylation patterns.

PMID- 15952896
TI  - Monitoring energy balance: metabolites of fatty acid synthesis as hypothalamic
      sensors.
AB  - Because energy balance is important for survival, a system is required to monitor
      energy status and to make appropriate adjustments in energy intake and energy
      expenditure. In higher animals, a centrally located system has evolved to
      accomplish this task. When caloric intake exceeds expenditure, the surplus is
      channeled into energy storage pathways, primarily the synthesis of fatty acids,
      which are converted into fat and stored in adipose tissue. Thus, metabolic flux
      through the pathway of fatty acid synthesis, located in the lipogenic tissues,
      reflects the "energy status" of the animal. The enzymatic machinery of this
      pathway is also expressed in the brain, notably the hypothalamus. In the
      hypothalamus, intermediates in this pathway appear to serve as energy sensors
      that signal higher brain centers to produce appropriate responses, e.g., altered
      food intake and energy expenditure.

PMID- 15952897
TI  - Structure and physiologic function of the low-density lipoprotein receptor.
AB  - The low-density lipoprotein receptor (LDLR) is responsible for uptake of
      cholesterol-carrying lipoprotein particles into cells. The receptor binds
      lipoprotein particles at the cell surface and releases them in the low-pH
      environment of the endosome. The focus of the current review is on biochemical
      and structural studies of the LDLR and its ligands, emphasizing how structural
      features of the receptor dictate the binding of low-density lipoprotein (LDL) and
      beta-migrating forms of very low-density lipoprotein (beta-VLDL) particles, how
      the receptor releases bound ligands at low pH, and how the cytoplasmic tail of
      the LDLR interfaces with the endocytic machinery.

PMID- 15952898
TI  - Copper-zinc superoxide dismutase and amyotrophic lateral sclerosis.
AB  - Copper-zinc superoxide dismutase (CuZnSOD, SOD1 protein) is an abundant copper-
      and zinc-containing protein that is present in the cytosol, nucleus, peroxisomes,
      and mitochondrial intermembrane space of human cells. Its primary function is to
      act as an antioxidant enzyme, lowering the steady-state concentration of
      superoxide, but when mutated, it can also cause disease. Over 100 different
      mutations have been identified in the sod1 genes of patients diagnosed with the
      familial form of amyotrophic lateral sclerosis (fALS). These mutations result in
      a highly diverse group of mutant proteins, some of them very similar to and
      others enormously different from wild-type SOD1. Despite their differences in
      properties, each member of this diverse set of mutant proteins causes the same
      clinical disease, presenting a challenge in formulating hypotheses as to what
      causes SOD1-associated fALS. In this review, we draw together and summarize
      information from many laboratories about the characteristics of the individual
      mutant SOD1 proteins in vivo and in vitro in the hope that it will aid
      investigators in their search for the cause(s) of SOD1-associated fALS.

PMID- 15952899
TI  - The structure and function of SMC and kleisin complexes.
AB  - Protein complexes consisting of structural maintenance of chromosomes (SMC) and
      kleisin subunits are crucial for the faithful segregation of chromosomes during
      cell proliferation in prokaryotes and eukaryotes. Two of the best-studied SMC
      complexes are cohesin and condensin. Cohesin is required to hold sister
      chromatids together, which allows their bio-orientation on the mitotic spindle.
      Cleavage of cohesin's kleisin subunit by the separase protease then triggers the
      movement of sister chromatids into opposite halves of the cell during anaphase.
      Condensin is required to organize mitotic chromosomes into coherent structures
      that prevent them from getting tangled up during segregation. Here we describe
      the discovery of SMC complexes and discuss recent advances in determining how
      members of this ancient protein family may function at a mechanistic level.

PMID- 15952900
TI  - DNA mismatch repair.
AB  - DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects
      mismatches generated during DNA replication and escape proofreading. MMR proteins
      also participate in many other DNA transactions, such that inactivation of MMR
      can have wide-ranging biological consequences, which can be either beneficial or
      detrimental. We begin this review by briefly considering the multiple functions
      of MMR proteins and the consequences of impaired function. We then focus on the
      biochemical mechanism of MMR replication errors. Emphasis is on structure
      function studies of MMR proteins, on how mismatches are recognized, on the
      process by which the newly replicated strand is identified, and on excision of
      the replication error.

PMID- 15952901
TI  - Gene therapy: twenty-first century medicine.
AB  - Broadly defined, the concept of gene therapy involves the transfer of genetic
      material into a cell, tissue, or whole organ, with the goal of curing a disease
      or at least improving the clinical status of a patient. A key factor in the
      success of gene therapy is the development of delivery systems that are capable
      of efficient gene transfer in a variety of tissues, without causing any
      associated pathogenic effects. Vectors based upon many different viral systems,
      including retroviruses, lentiviruses, adenoviruses, and adeno-associated viruses,
      currently offer the best choice for efficient gene delivery. Their performance
      and pathogenicity has been evaluated in animal models, and encouraging results
      form the basis for clinical trials to treat genetic disorders and acquired
      diseases. Despite some initial success in these trials, vector development
      remains a seminal concern for improved gene therapy technologies.

PMID- 15952902
TI  - The mammalian unfolded protein response.
AB  - In the endoplasmic reticulum (ER), secretory and transmembrane proteins fold into
      their native conformation and undergo posttranslational modifications important
      for their activity and structure. When protein folding in the ER is inhibited,
      signal transduction pathways, which increase the biosynthetic capacity and
      decrease the biosynthetic burden of the ER to maintain the homeostasis of this
      organelle, are activated. These pathways are called the unfolded protein response
      (UPR). In this review, we briefly summarize principles of protein folding and
      molecular chaperone function important for a mechanistic understanding of UPR
      signaling events. We then discuss mechanisms of signal transduction employed by
      the UPR in mammals and our current understanding of the remodeling of cellular
      processes by the UPR. Finally, we summarize data that demonstrate that UPR
      signaling feeds into decision making in other processes previously thought to be
      unrelated to ER function, e.g., eukaryotic starvation responses and
      differentiation programs.

PMID- 15952903
TI  - The structural biology of type II fatty acid biosynthesis.
AB  - The type II fatty acid synthetic pathway is the principal route for the
      production of membrane phospholipid acyl chains in bacteria and plants. The
      reaction sequence is carried out by a series of individual soluble proteins that
      are each encoded by a discrete gene, and the pathway intermediates are shuttled
      between the enzymes as thioesters of an acyl carrier protein. The Escherichia
      coli system is the paradigm for the study of this system, and high-resolution X
      ray and/or NMR structures of representative members of every enzyme in the type
      II pathway are now available. The structural biology of these proteins reveals
      the specific three-dimensional features of the enzymes that explain substrate
      recognition, chain length specificity, and the catalytic mechanisms that define
      their roles in producing the multitude of products generated by the type II
      system. These structures are also a valuable resource to guide antibacterial drug
      discovery.

PMID- 15952904
TI  - Structural studies by electron tomography: from cells to molecules.
AB  - Electron tomography (ET) is uniquely suited to obtain three-dimensional
      reconstructions of pleomorphic structures, such as cells, organelles or
      supramolecular assemblies. Although the principles of ET have been known for
      decades, its use has gathered momentum only in recent years, thanks to
      technological advances and its combination with improved specimen preparation
      techniques. The rapid freezing/freeze-substitution preparation is applicable to
      whole cells and tissues, and it is the method of choice for ET investigations of
      cellular ultrastructure. The frozen-hydrated preparation provides the best
      possible structural preservation and allows the imaging of molecules, complexes,
      and supramolecular assemblies in their native state and their natural
      environment. Devoid of staining and chemical fixation artifacts, cryo-ET provides
      a faithful representation of both the surface and internal structure of
      molecules. In combination with advanced computational methods, such as molecular
      identification based on pattern recognition techniques, cryo-ET is currently the
      most promising approach to comprehensively map macromolecular architecture inside
      cellular tomograms.

PMID- 15952905
TI  - The potential of exosomes in immunotherapy.
AB  - In 1996, B cell-derived exosome immunogenicity was first reported. In 1998,
      dendritic cell-derived exosomes were also shown to have immunogenic properties in
      mice, leading to tumour eradication. These observations showed for the first time
      that exosomes were bioactive vesicles with immuno-regulatory roles and potent
      antitumour effects. Exosomes are secreted vesicles formed in late endocytic
      compartments (multivesicular bodies). Vesicles exocytosed from multivesicular
      bodies into the extracellular medium are referred to as 'exosomes' and should not
      be confused with the more recently described 'ribonuclease complex' also named
      exosome. Exosomes are vesicles of 50-100 nm in diameter, formed by inward budding
      of the endosomal membrane in a process that sequesters particular proteins and
      lipids. This review will describe the biogenesis, the protein and lipid
      compositions, and the biological functions of exosomes; this review will also
      present their immunostimulatory functions in mice and humans, and will discuss
      their possible use as cancer vaccines.

PMID- 15952906
TI  - Interferon alpha for the treatment of advanced renal cancer.
AB  - This paper is an overview on the place of IFN-alpha in metastatic renal cell
      carcinoma (MRCC). After a presentation of MRCC and the mode of action of IFN
      alpha, the results of studies including IFN-alpha alone or in combination with IL
      2, chemotherapy and other biological modifiers are presented. Finally, new trends
      for new drugs, including antiangiogenic therapies, are discussed.

PMID- 15952907
TI  - Gene therapeutics in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a complex autoimmune disorder, characterised by
      mononuclear cell infiltration of exocrine glands, principally the lacrimal and
      salivary glands. Both cellular, in the form of autoreactive immune cells, and
      humoral factors, such as autoantibodies, contribute to the expression of the
      disease. SS can also occur as a systemic disease affecting several organs, and
      approximately 5% of the patients develop malignant lymphoproliferation. Today SS
      is considered uncurable. The treatment available is only palliative, and the
      treatment goals are to manage symptoms and prevent or limit tissue damage. This
      may involve both local and systemic measures. However, the existing systemic
      treatment of chronic inflammatory autoimmune diseases has several limitations and
      unwanted side effects. In recent years the possibility to treat diseases with
      gene therapy has gained interest and has become a subject of investigation. Given
      the multitude of factors contributing to the pathogenesis of SS, gene therapy is
      a major challenge, but may elicit great benefits if successful. Keeping this in
      mind, the possibility for gene therapeutics in SS in general and potential
      targets for gene therapy are discussed.

PMID- 15952908
TI  - Bacteriophage-mediated protein delivery into the central nervous system and its
      application in immunopharmacotherapy.
AB  - Cocaine addiction continues to be a major health and social problem in spite of
      governmental efforts devoted towards educating the public in the dangers of
      illicit drug use. A variety of pharmacotherapies and psychosocial programmes have
      been proposed in an effort to provide a method for alleviating the physical and
      psychological symptoms of cocaine abuse. Unfortunately, these methods have been
      met with limited success, illustrating a critical need for new effective
      approaches for the treatment of cocaine addiction. The authors have recently
      disclosed an alternative cocaine abuse treatment strategy using intranasal
      administration of an engineered filamentous bacteriophage displaying cocaine
      sequestering antibodies on its surface. These phage particles are an effective
      vector for central nervous system penetration and are capable of binding cocaine,
      thereby blocking its behavioural effects in a rodent model.

PMID- 15952909
TI  - Peptide aptamers: recent developments for cancer therapy.
AB  - During the past two decades, our understanding of oncogenesis has advanced
      considerably and many new signalling pathways have been identified. Differences
      in signalling events that distinguish normal cells from tumour cells provide new
      targets for the development of anticancer agents. Peptide aptamers are small
      peptide sequences that have been selected to recognise a predetermined target
      protein domain and are potentially able to interfere with its function. They
      represent useful molecules for manipulating protein function in vivo. The
      isolation and use of specific peptide aptamers as inhibitors of individual
      signalling components, essential in cancer development and progression, provides
      a new challenge for drug development. Although peptides make up only a small
      fraction of current therapeutics, their potential is being enhanced by new
      developments affecting their modification, stability, delivery and their
      successful application in preclinical settings. This review summarises the
      methods that can be used for the isolation and delivery of peptide aptamers, as
      well as the important achievements that have been made using such peptide
      aptamers in different systems. The applicability of peptide aptamers as novel
      cancer therapeutics will be discussed.

PMID- 15952910
TI  - Peptide-based vaccination for colorectal cancer.
AB  - Recently, the number of patients with colorectal cancer has been increasing.
      Although most patients with early colorectal cancer have a good prognosis, in the
      case of recurrent or metastatic disease, the prognosis is poor and most patients
      will ultimately die of cancer. Furthermore, the conventional treatment, such as
      chemotherapy or radiation therapy, occasionally can not be continued due to
      reasons of toxicity and/or poor response. Therefore, novel therapeutic optional
      approaches based on immunotherapy are being explored at present. This review
      describes and sums up the principles and the longstanding problems of peptide
      vaccine therapy, and demonstrates the results of clinical trials with colorectal
      cancer peptide vaccine therapy, including the authors' personal appraisal. In
      conclusion, the future prospects of peptide vaccine therapy are described.

PMID- 15952911
TI  - Refining an Alzheimer's vaccine to avoid an inflammatory response.
AB  - The utility of vaccine strategies to treat neurodegenerative diseases such as
      Alzheimer's disease may still hold promise. Phase IIa clinical trials were halted
      due to a small but significant occurrence of meningoencephalitis. Knowledge
      gained from studies on amyloid-beta peptide (Abeta) immunotherapy will allow
      optimisation of new-generation vaccines, targeting highly specific epitopes while
      reducing undesired side effects. In harnessing and steering the immune system, an
      effective response can be generated against Abeta, one that might have attenuated
      immune responses with robust disease-altering activity.

PMID- 15952912
TI  - New therapeutic agents for the treatment of bone diseases.
AB  - Bisphosphonates have demonstrated important clinical benefits for patients with
      malignant bone disease, metabolic bone diseases, such as Paget's disease, and
      postmenopausal osteoporosis. The introduction of nitrogen-containing
      bisphosphonates with high affinity for hydroxyapatite in bone represents an
      important advancement. These agents are now a standard of care for osteoporosis,
      Paget's disease, osteogenesis imperfecta, primary bone lesions from multiple
      myeloma and bone metastases from breast cancer. Moreover, the recent clinical
      development of zoledronic acid (4 mg by 15-minute intravenous infusion) has
      expanded the benefits of bisphosphonate therapy to patients with bone metastases
      from any solid tumour. Bisphosphonates are also being investigated at present for
      the prevention of bone loss resulting from cancer therapy. In addition, a variety
      of novel biologic agents, receptor activator of nuclear factor-kappaB (RANK)
      ligand antibodies, osteoprotegerin and cathepsin K inhibitors are being
      investigated at present for the treatment of malignant bone disease. The
      management of bone health is an important area of active research, and the
      armamentarium and role of bone-specific therapies continue to expand.

PMID- 15952913
TI  - Pexelizumab -- a C5 complement inhibitor for use in both acute myocardial
      infarction and cardiac surgery with cardiopulmonary bypass.
AB  - Myocardial injury and dysfunction in acute infarction and during cardiac surgery
      with cardiopulmonary bypass (CPB) are associated with an undesirable systemic
      inflammatory response, in which the complement cascade plays a major role. In
      animal models C5 inhibition has been found to significantly reduce myocardial
      infarct size and decrease cellular necrosis and apoptosis. Pexelizumab (Alexion
      Pharmaceuticals, Inc., Cheshire, CT, USA) is a humanized, monoclonal, single
      chain antibody fragment that inhibits C5, thereby blocking its cleavage into
      active forms. Prospective, randomised, double-blind, placebo-controlled trials
      using pexelizumab during percutaneous coronary intervention following acute
      myocardial infarction (AMI), or in patients undergoing coronary artery bypass
      graft (CABG) with CPB, have demonstrated a reduction in morbidity and mortality.
      Thus, pexelizumab represents a promising therapeutic option with sustained
      benefit both in AMI and during CABG with CPB.

PMID- 15952914
TI  - Recombinant, tumour-derived idiotype vaccination for indolent B cell non
      Hodgkin's lymphomas: a focus on FavId.
AB  - FavId (Favrille, Inc., San Diego, CA, USA) is a personalized therapeutic vaccine
      product for B cell non-Hodgkin's lymphoma, custom-manufactured from individual
      patient's tumour cells. This investigational agent consists of recombinant tumour
      specific immunoglobulin (idiotype [Id]) chemically conjugated to the highly
      immunogenic carrier protein keyhole limpet haemocyanin (Id-KLH). The vaccine
      product is administered by subcutaneous co-injection with the cytokine adjuvant
      granulocyte-macrophage colony-stimulating factor (GM-CSF) with the goal of
      stimulating tumour-specific T cell and humoral immunity. Therapeutic Id vaccines
      have shown promising results in early phase clinical trials in follicular
      lymphoma, and several Phase III trials are ongoing. FavId's advantages over other
      Id vaccine formulations include its rapid and efficient manufacturing technology
      utilising recombinant baculovirus, with a production time of only 8-12 weeks. In
      Phase II studies, FavId Id-KLH plus GM-CSF vaccines have been found to be safe,
      immunogenic and clinically active in follicular lymphoma. At present, FavId is
      being tested in a randomised, placebo-controlled Phase III trial in follicular
      lymphoma, aimed at improving the time to disease progression when administered
      following cytoreduction with rituximab. If found to be efficacious in this
      pivotal trial, FavId would represent a tumour-selective immunotherapy for
      lymphoma with little toxicity and a novel mechanism of action.

PMID- 15952915
TI  - A monoclonal antibody as an effective therapeutic agent in breast cancer:
      trastuzumab.
AB  - Trastuzumab (Herceptin; Genentech, Inc., CA, USA) is a humanized monoclonal
      antibody developed to target the HER-2/neu receptor, which is overexpressed in 20
      - 25% of breast carcinomas. Clinical studies showed that trastuzumab is effective
      as single-agent therapy and that it has greater antitumour activity in
      combination with chemotherapy than chemotherapy alone in metastatic breast
      cancer. The indication for trastuzumab monotherapy and the combination with
      various chemotherapy agents is country-specific and is largely based on trials of
      efficacy and safety. Patients with a HER-2/neu overexpression level of 3+,
      determined by immunohistochemical assay or amplification using fluorescence in
      situ hybridisation, derive most clinical benefit from trastuzumab. Trastuzumab is
      generally well-tolerated. Cardiotoxicity is the main concern; thus, monitoring of
      cardiac function is recommended. Ongoing trials investigate the role of
      trastuzumab in the adjuvant and neoadjuvant settings.

PMID- 15952916
TI  - An update on the pharmacological management of hyperthyroidism due to Graves'
      disease.
AB  - Pharmacological treatment, usually by thionamides (carbimazole, methimazole,
      propylthiouracil) is, in addition to radioiodine therapy and thyroidectomy, one
      of the available therapies for Graves' hyperthyroidism. Thionamides represent the
      treatment of choice in pregnant women, during lactation, in children and
      adolescents and in preparation for radioiodine therapy or thyroidectomy. Side
      effects are relatively frequent but are in general mild and transient. Two main
      regimens are available: titration method (use of the lowest dose maintaining
      euthyroidism; duration: 12-18 months) and block-and-replace method. Neither one
      has clear advantages in terms of outcome but the latter method is associated with
      more frequent side effects. Hyperthyroidism relapses in approximately 50% of
      patients, to whom ablative therapy should be offered.

PMID- 15952917
TI  - Therapeutic perspectives of adipocytokines.
AB  - Various adipocyte-secreted factors have been described which profoundly affect
      insulin sensitivity and might potentially link obesity, insulin resistance and
      cardiovascular disease. Among those, adiponectin, visfatin and omentin appear as
      insulin-sensitising adipocytokines, whereas TNF-alpha, IL-6 and resistin induce
      insulin resistance. Moreover, leptin is a fat-derived key regulator of appetite
      and energy expenditure. Due to their profound effect on whole-body glucose and
      energy metabolism, adipocytokines have attracted interest as potential new
      therapeutics for diabetes mellitus and obesity. The current knowledge on
      function, regulation and therapeutic potential of various adipocytokines, as well
      as their clinical implications, are discussed in this review.

PMID- 15952918
TI  - Defining the need for new antimicrobials: clinical and economic implications of
      resistance in the hospitalised patient.
AB  - Resistance among pathogens causing the most common infections encountered in
      hospitalised patients is increasing. Due to this resistance, the clinical
      efficacy of current antimicrobial agents is decreasing against many pathogens,
      including Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus,
      vancomycin-resistant enterococci, Pseudomonas aeruginosa, extended-spectrum beta
      lactamases, and AmpC beta-lactamase-producing organisms. Studies assessing the
      impact of these resistance mechanisms on clinical outcomes have been performed;
      however, studies determining the economic impact of resistance have been limited.
      Strategies to retain the clinical efficacy of currently available agents include
      the initiation of antimicrobials with efficacy against the suspected pathogen(s)
      based on data obtained from local antibiograms, the use of combination therapy,
      and pharmacodynamic optimisation. Once a broad-spectrum regimen has been
      initiated, de-escalation to narrow, targeted antimicrobial therapy based on
      susceptibility data is warranted. Despite these efforts, new antimicrobials with
      novel mechanisms of action are eagerly anticipated to extend the current
      armamentarium against the growing population of multi-drug-resistant pathogens.

PMID- 15952919
TI  - Pharmacotherapy, vaccines and malaria advice for HIV-infected travellers.
AB  - Since the introduction of effective antiretroviral therapy (ART), HIV-infected
      individuals are travelling more frequently and international travel has become
      much safer. Specific concerns include the safety of ART during travel, drug
      adherence and interaction considerations, and effects of immunosuppression. This
      review describes potentially important infections, vaccine effectiveness, safety
      and special approaches for their use, and HIV-related issues regarding
      predeparture counselling. With advanced immunosuppression (CD4+ T-cell count <
      200/microl or < 14%), the immunogenicity of several vaccines is reduced,
      complications could occur after live attenuated vaccines and certain infections
      acquired during travel may be more frequent or severe. Challenges include the
      best options for malaria chemoprophylaxis, standby treatment and medical follow
      up of the increasing number of HIV-infected long-term travellers.

PMID- 15952921
TI  - Cardiovascular risk in chronic renal disease and transplantation prevention and
      management.
AB  - Cardiovascular disease (CVD) is the single best predictor of mortality in
      patients with chronic kidney disease and in kidney transplant recipients. These
      populations are considered to be at extraordinarily high risk for CVD and its
      complications. On the other hand, renal dysfunction should be considered as a CVD
      risk factor. The management of CVD in patients with chronic kidney disease is a
      special challenge for clinicians. In this article, major risk factors for CVD are
      presented, as well as diagnosis of coronary artery disease, acute coronary
      syndromes, its treatment modalities (pharmacological therapy and coronary
      revascularisation procedures), and outcomes in patients with chronic renal
      failure and kidney allograft recipients.

PMID- 15952920
TI  - Atorvastatin and cardiovascular protection: a review and comparison of recent
      clinical trials.
AB  - Until recently, atorvastatin was known only as a new but more potent statin ('me
      too' drug) for lowering low-density lipoprotein cholesterol. In the last 2 years,
      data has become available on nearly 32,000 patients, in clinical settings ranging
      from primary prevention to acute coronary syndromes. These trials show the
      remarkably consistent clinical benefit of atorvastatin in patients with
      hypertension, diabetes, acute coronary syndromes, stable coronary disease with
      reductions in death, myocardial infarction and stroke, as well as in prevention
      of atherosclerosis progression. In addition, new data are also emerging to
      suggest that intensive therapy with high dose atorvastatin 80 mg is associated
      with a greater reduction in inflammatory markers, such as C-reactive protein,
      compared with other statin regimens. This suggests that intensive therapy with
      atorvastatin is associated with a potent pleiotropic effect. This review aims to
      summarise the recently concluded and ongoing clinical trials and to stimulate
      further reading.

PMID- 15952922
TI  - Treatment options for POEMS syndrome.
AB  - POEMS syndrome is a rare paraneoplastic syndrome secondary to a plasma cell
      dyscrasia. Recognition of the complex of a combination of peripheral neuropathy,
      organomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin
      changes, sclerotic bone lesions, Castleman's disease, thrombocytosis,
      papilledema, peripheral oedema, pleural effusions, ascites, fingernail clubbing
      and white nails, is the first step in effectively managing the disease. More than
      95% of patients will have monoclonal lambda sclerotic plasmacytoma(s) or bone
      marrow infiltration. In patients with a dominant sclerotic plasmacytoma, first
      line therapy should include radiation to the lesion. Retrospective analysis and
      personal experience would dictate that systemic therapy be considered for
      patients with diffuse sclerotic lesions or absence of any bone lesion, and for
      those who have not demonstrated stabilisation of their disease 3-6 months after
      completing radiation therapy. For those patients with diffuse disease, systemic
      therapy is indicated. Useful approaches include therapy with corticosteroids, low
      dose alkylator therapy and high dose chemotherapy with peripheral blood stem cell
      transplant. Until the pathogenesis is fully understood, these are the mainstays
      of treatment for patients with POEMS syndrome.

PMID- 15952923
TI  - Use of medications in Wolff-Parkinson-White syndrome.
AB  - The diagnosis of Wolff-Parkinson-White syndrome is generally straightforward;
      however, the management may not be, and requires an understanding of the
      competing risks of various treatment options and that of the clinical setting in
      which the diagnosis is made. The symptomatic patient with Wolff-Parkinson-White
      has an increased risk of atrial fibrillation and a small but significant risk of
      sudden cardiac death. Therapy is based on reduction in symptom burden and
      attenuation of the risk of pre-excited atrial fibrillation. Catheter ablation is
      the most effective means of achieving this goal with abolition of symptoms and
      risk of pre-excited atrial fibrillation. Medication is often employed in the
      acute setting to terminate paroxysms of arrhythmia associated with the accessory
      pathway and reduce the subsequent burden of symptoms until ablation can be
      performed. An overview of the agents commonly used is provided together with
      recommendations.

PMID- 15952924
TI  - Decision models for assessing the cost effectiveness of drug-eluting stents.
AB  - Percutaneous coronary intervention is an increasingly common treatment for many
      people with coronary disease. Randomised trials using antiproliferative, drug
      eluting stents (DES) have shown important reductions in the need for repeat
      procedures after initial percutaneous coronary intervention. These trials
      indicate that the growing use of DES has the potential to create major clinical
      benefits for patients; however, in actual practice, the associated costs may
      cause financial crises for hospital systems. This paper reviews previously
      published DES economic decision models from both societal and hospital
      perspectives. From a social perspective, additional spending for new technologies
      may be acceptable if these technologies convincingly improve the lives of
      patients. The models reviewed suggest that DES incurs large costs to both society
      and hospitals, and currently offers uncertain clinical benefits. More research is
      recommended to identify high-risk patients who stand to gain significant health
      benefits from this therapy.

PMID- 15952925
TI  - Pharmacological strategies for trichotillomania.
AB  - Pharmacotherapy for trichotillomania (TTM) is not well established, due to a
      paucity of positive, controlled, long-term studies. Although selective-serotonin
      re-uptake inhibitors (SSRIs) seem to be the safest and best-established
      medication choices, positive treatment response is not consistent in the
      literature. Treatment response is often disrupted by significant relapse.
      Behavioural therapy may be a more effective treatment for some patients. For
      other patients, other antidepressants, neuroleptics or even topical agents may be
      helpful. Future investigations should include more controlled studies and longer
      observation for relapse.

PMID- 15952926
TI  - Gefitinib in non-small cell lung cancer.
AB  - Gefitinib (Iressa), an orally-active tyrosine kinase inhibitor of the epidermal
      growth factor receptor (EGFR), is the first approved molecular-targeted drug for
      the management of patients with advanced non-small cell lung cancer (NSCLC). Two
      Phase II trials (IDEAL [Iressa Dose Evaluation in Advanced Lung Cancer]-1 and 
      2), evaluated the efficacy of gefitinib in advanced NSCLC patients who received <
      or = 2 (IDEAL1) or > or = 2 (IDEAL2) previous chemotherapy regimens. The response
      rate and disease control rate in IDEAL1 and -2 was 18/12% and 54/42%,
      respectively. The median survival time and one-year survival rate in both studies
      were approximately 7 months and 30%, respectively. As gefitinib has demonstrated
      antitumour activity and an acceptable tolerability profile not typically
      associated with cytotoxic adverse events, such as hematological toxicities,
      combinations with cytotoxic drugs have been evaluated. Disappointingly, in
      chemotherapy-naive patients with advanced NSCLC, gefitinib 250 and 500 mg/day
      combined with platinum-based chemotherapy (gemcitabine/cisplatin or
      paclitaxel/carboplatin) did not produce prolonged survival, compared with
      chemotherapy alone in two large, randomised, placebo-controlled, multi-centre
      Phase III trials (INTACT [Iressa NSCLC Trial Assessing Combination Treatment]-1
      and -2). Furthermore, in a recent randomised, placebo-controlled, Phase III trial
      (ISEL: IRESSA Survival Evaluation in Lung cancer), gefitinib failed to prolong
      survival compared with placebo in patients with advanced NSCLC who had failed one
      or more lines of chemotherapy. Subgroup analysis of ISEL suggested improved
      survival in patients of Asian origin and non-smokers. In addition, subset
      analyses of IDEAL and several retrospective studies have indicated that female
      gender, adenocarcinoma histology (especially bronchial alveolar carcinoma), non
      smoker status and Asian ethnicity are factors which predict to response to
      gefitinib. Two types of somatic mutation clustered around the ATP binding pocket
      in the tyrosine kinase domain of the EGFR gene have been reported as possible
      surrogate biological markers for predicting response to gefitinib. Appropriate
      patient selection by clinical characteristics or genetical information is needed,
      both for future clinical trials of gefitinib and its routine use in the clinic
      among patients with advanced NSCLC.

PMID- 15952927
TI  - Erlotinib in non-small cell lung cancer: a review.
AB  - Erlotinib (Tarceva, OSI-774; Pfizer, Inc.) is an orally-active, targeted
      inhibitor of the epidermal growth factor receptor (EGFR/HER1), which is part of a
      key regulatory pathway in cancer. Patients with advanced, incurable non-small
      cell lung cancer (NSCLC) may derive a clinical benefit from first- and second
      line chemotherapy, but third-line treatment with available cytotoxic agents is
      not effective. Remarkably, EGFR/HER1 antagonists have demonstrated activity as
      second- and even third-line treatment for this disease. Erlotinib is the first of
      this novel class of drug to demonstrate a statistically significant and
      clinically relevant difference in overall survival, progression free survival and
      time to disease related symptoms (cough, pain, shortness of breath) compared with
      treatment with best supportive care in patients who have failed standard first-
      or second-line chemotherapy. This paper reviews the pharmacology, preclinical and
      clinical data to support the use of erlotinib in NSCLC.

PMID- 15952928
TI  - Safety, efficacy and extended duration of action of mixed amphetamine salts
      extended-release capsules for the treatment of ADHD.
AB  - Stimulant medications have proven to be effective in reducing the core symptoms
      of hyperactivity, impulsivity and inattention and are considered the first line
      of therapy for patients with attention-deficit/hyperactivity disorder (ADHD).
      Mixed amphetamine salts extended-release capsules (MAS XR; Adderall XR, Shire
      Pharmaceuticals Group) include immediate-release pellets of mixed amphetamine
      salts that release the first half of the dose upon ingestion and delayed-release
      pellets that begin to release active drug approximately 4 h later. The MAS XR
      capsule contains the same 3:1 ratio of dextroamphetamine to levoamphetamine as do
      mixed amphetamine salts immediate-release tablets (MAS IR; Adderall), Shire
      Pharmaceuticals Group), and the bioavailability and pharmacokinetic profiles of
      MAS XR 20 mg are comparable to those with MAS IR 10 mg b.i.d. MAS XR has a rapid
      onset of action--within 1.5 h--and provides 12 h coverage. The efficacy, safety
      and extended duration of action of MAS XR have been established through clinical
      studies in school-age children, adolescents and adults.

PMID- 15952929
TI  - Intranasal zolmitriptan.
AB  - Intranasal zolmitriptan has recently been launched in the US and Canada and is a
      novel formulation of the antimigraine drug zolmitriptan. This drug has been used
      extensively in its oral formulation. The intranasal formulation offers a more
      rapid onset of action. Pharmacokinetic studies have demonstrated that it is
      absorbed rapidly into the systemic circulation and traces can be seen in the
      brain within 5 min. The onset of efficacy in the Real Life Intranasal
      Zolmitriptan Exposure (REALIZE) study was measurable at 10 min and at 15 min in
      the US 22 study, which demonstrates rapid absorption and effect at the 5
      HT(1B/1D) receptors. This article reviews the initial studies of intranasal
      zolmitriptan; three of the most recent studies will be examined in detail.

PMID- 15952930
TI  - Recent important trials of pharmacotherapy in Parkinson's disease.
AB  - Parkinson's disease (PD) affects approximately 1% of individuals > 60 years. Of
      these PD patients approximately 40% suffer dementia in later life. Levodopa is
      commonly used in the treatment of PD. Experimental evidence suggests that the
      dopamine synthesised from levodopa may contribute to the further degeneration of
      dopaminergic neurons. The results of the clinical outcome part of the Earlier
      Versus Later Levodopa Therapy in PD study suggest that levodopa slows the
      progression of PD. In contrast, the single photon emission-computed tomography
      imaging substudy was not conclusive but suggested that levodopa hastened the
      progression of PD. Thus, further studies of the effects of levodopa on the
      progression of PD are needed before it can be proved that levodopa does not have
      a detrimental effect on dopaminergic neurons. In a clinical trial of the
      anticholinesterase rivastigmine, a small improvement was observed in some
      patients suffering from dementia associated with PD. This small benefit has to be
      balanced against cholinergic side effects and a possible loss of efficacy of
      antimuscarinic agents used for motor control in PD.

PMID- 15952931
TI  - Th1 and Th2 lymphocytes in autoimmune disease.
AB  - This review reconsiders how the Th1/Th2 paradigm can be applied to Th1-mediated
      autoimmune disease. Although there is evidence that autoimmune diseases such as
      multiple sclerosis, type 1 insulin-dependent diabetes mellitus, and posterior
      uveitis are Th1 mediated and that in some cases reduction of the Th1 response or
      a Th2 type shift may alleviate disease, many apparent exceptions are now well
      documented. These exceptions center around the contradictory actions of the Th1
      cytokine IFN-gamma and the evidence that Th2 lymphocytes can also cause disease.
      Recent information on the regulation of Th1 and Th2 lymphocytes in terms of the
      innate immune response and by other T cells helps to clarify the reasons for some
      of these discrepancies and enables the Th1/Th2 concept to be accepted as an
      integral part of the complex interactions occurring as autoimmune disease
      develops.

PMID- 15952932
TI  - Platelet activation and the CD40/CD40 ligand pathway: mechanisms and implications
      for human disease.
AB  - The discovery that platelets express CD40 and the CD40 ligand has transformed
      these cells, once seen as exclusively involved in coagulation and thrombosis,
      into active players of immunity and inflammatory injury. Many of the broad and
      potent biological activities mediated through the CD40/CD40 pathway by immune and
      nonimmune cells are also exerted by activated platelets. This occurs either
      through the constitutive expression of CD40 on the platelet surface or the
      activation-induced expression of the CD40 ligand, which is membrane bound and
      released from the surface in a soluble form. The most prominent activities
      mediated by the platelet CD40/CD40 ligand pathway include inflammatory,
      immunoregulatory, and hemostatic functions, all of which contribute to the newly
      expanded view of platelets as key biological mediators involved in disease
      processes such as atherosclerosis, inflammatory bowel disease, and diabetes.
      Therefore, considering platelet CD40 and CD40 ligand as novel biological targets
      is justified and supported by animal studies. The clinical profit to be gained
      from blocking this molecular pair will be determined by results in humans with
      conditions in which the platelet CD40/CD40 ligand pathway is crucially involved
      in disease pathogenesis.

PMID- 15952933
TI  - T- and B-cell abnormalities in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized
      by the production of antinuclear autoantibodies and clinical involvement in
      multiple organ systems. T cells from patients with SLE have been shown to be
      activated in vivo and provide help to autoreactive B cells. Abnormal expression
      of key signaling molecules, defective signal transduction pathways, and permanent
      mitochondrial dysfunction--associated with a significantly increased
      mitochondrial mass--appear to be the axis of T-lymphocyte dysfunction. Lupus T
      cells exhibit persistent mitochondrial hyperpolarization (MHP), cytoplasmic
      alkalinization, increased ROI production, and ATP depletion that mediate enhanced
      spontaneous and diminished activation-induced apoptosis and sensitize lupus T
      cells to necrosis. Necrotic, but not apoptotic, cell lysates activate dendritic
      cells and may account for increased interferon-alpha production, inflammation,
      and antinuclear antibody production. Recent data indicate that B cells are not
      merely the passive producers of autoantibodies, but also play a central role in
      autoimmunity via nonconventional mechanisms, including autoantigen presentation
      and modulation of other immune cells. This article reviews recent advancements in
      the understanding of the molecular mechanisms involved in the pathogenesis of
      lupus autoimmunity and highlights the development of novel therapies in SLE.

PMID- 15952934
TI  - Thymus-derived signals regulate early T-cell development.
AB  - T cells develop in the thymus from uncommitted progenitors under the influence of
      multiple soluble and membrane-associated factors that regulate the migration,
      survival, proliferation, and differentiation of progenitor thymocytes. The role
      of cytokines such as stem cell factor and IL-7 in this process is well
      established. However, several recent studies have demonstrated an important role
      for other soluble factors in T-cell development, including WNTs, bone
      morphogenetic proteins, and Hedgehog proteins. Other studies have clarified how
      chemokines regulate the migration of progenitor thymocytes at various stages of
      development. Furthermore, the Notch pathway has emerged as the critical inducer
      of T-lineage commitment and differentiation, and Notch ligands expressed by the
      thymic stroma likely provide essential developmental cues throughout early T-cell
      development. In this review, we discuss recent advances in our understanding of
      how thymus-derived signals regulate early T-cell development.

PMID- 15952935
TI  - Modification of epithelial tight junction integrity to enhance transmucosal
      absorption.
AB  - Tight junctions (TJs) located between adjacent epithelial cells restrict the
      movement of solutes, ions, and even water. Restriction of macromolecules by TJ
      structures impedes one potential route of absorption for biopharmaceutical drugs,
      a route known as the paracellular pathway. It is anticipated that an improved
      understanding of TJ structure and cellular mechanisms that regulate its function
      will lead to successful strategies for improved transmucosal drug absorption
      through the paracellular pathway. Based upon clinical correlations between TJ
      dysfunction and several disease states, any approach to modify TJ integrity to
      enhance drug absorption in this way must be tempered by an appreciation of
      potential safety concerns that might develop through sustained or repeated TJ
      alterations. This review describes a current understanding of epithelial TJ
      organization and examines potential methods and implications for regulated
      modification of TJ function for the enhanced uptake of drugs without detrimental
      clinical outcomes.

PMID- 15952936
TI  - Alphab-crystallin-assisted reactivation of glucose-6-phosphate dehydrogenase upon
      refolding.
AB  - Alphab-crystallin, a small heat-shock protein has been shown to prevent the
      aggregation of other proteins under various stress conditions. We have
      investigated the role of alphaB-crystallin in the reactivation of denaturant
      [GdmCl (guanidinium chloride)]-inactivated G6PD (glucose-6-phosphate
      dehydrogenase). Studies indicate that unfolding and inactivation of G6PD by GdmCl
      proceeds via formation of a molten globule-like state at low concentrations of
      GdmCl, which was characterized by having maximum surface hydrophobicity and no
      catalytic activity. At high concentrations of GdmCl, G6PD was completely
      unfolded, which upon dilution-induced refolding yielding 35% of original
      activity. In contrast, no activity was recovered when G6PD was refolded from a
      molten globule-like state. Interestingly, refolding of completely unfolded G6PD
      in the presence of alphaB-crystallin resulted in 70% gain of the original
      activity, indicating that alphaB-crystallin assisted in enhanced refolding of
      G6PD. Intriguingly, alphaB-crystallin was unable to reactivate G6PD from a molten
      globule-like state. Size-exclusion chromatography data indicate that alphaB
      crystallin-assisted reactivation of completely unfolded G6PD is concomitant with
      the restoration of the native structure of G6PD. Nonetheless, alphaB-crystallin
      failed to reactivate G6PD from preformed aggregates. Moreover, methylglyoxal
      modified alpha-crystallin, which occurs in aged and diabetic cataract lenses, was
      less efficient in the reactivation of denaturant inactivated G6PD. Diminished
      chaperone-like activity of alpha-crystallin due to post-translational
      modifications may thus result in the accumulation of aggregated/inactivated
      proteins.

PMID- 15952937
TI  - Participation of both Gab1 and Gab2 in the activation of the ERK/MAPK pathway by
      epidermal growth factor.
AB  - Three members of Gab family docking proteins, Gab1, Gab2 and Gab3, have been
      identified in humans. Previous studies have found that the hepatocyte growth
      factor preferentially utilizes Gab1 for signalling, whereas Bcr-Abl selectively
      signals through Gab2. Gab1-SHP2 interaction has been shown to mediate ERK
      (extracellular-signal-regulated kinase) activation by EGF (epidermal growth
      factor). However, it was unclear whether EGF selectively utilizes Gab1 for
      signalling to ERK and whether Gab2 is dispensable in cells where Gab1 and Gab2
      are co-expressed. Using T47D and MCF-7 human breast carcinoma cells that express
      endogenous Gab1 and Gab2, we examined the role of these docking proteins in EGF
      induced ERK activation. It was found that EGF induced a similar amount of SHP2
      Gab1 and SHP2-Gab2 complexes. Expression of either SHP2-binding defective Gab1 or
      Gab2 mutant blocked EGF-induced ERK activation. Down-regulation of either Gab1 or
      Gab2 by siRNAs (small interfering RNAs) effectively inhibited the EGF-stimulated
      ERK activation pathway and cell migration. Interestingly, the inhibitory effect
      of Gab1 siRNA could be rescued not only by expression of an exogenous mouse Gab1
      but also by an exogenous human Gab2 and vice versa, but not by IRS1 (insulin
      receptor substrate 1). These results reveal that Gab2 plays a pivotal role in the
      EGF-induced ERK activation pathway and that it can complement the function of
      Gab1 in the EGF signalling pathway. Furthermore, Gab1 and Gab2 are critical
      signalling threshold proteins for ERK activation by EGF.

PMID- 15952938
TI  - Identification of the hydrophobic strand in the A-B loop of leptin as major
      binding site III: implications for large-scale preparation of potent recombinant
      human and ovine leptin antagonists.
AB  - Interaction of leptin with its receptors resembles that of interleukin-6 and
      granulocyte colony-stimulating factor, which interact with their receptors
      through binding sites I-III. Site III plays a pivotal role in receptors'
      dimerization or tetramerization and subsequent activation. Leptin's site III also
      mediates the formation of an active multimeric complex through its interaction
      with the IGD (immunoglobulin-like domain) of LEPRs (leptin receptors). Using a
      sensitive hydrophobic cluster analysis of leptin's and LEPR's sequences, we
      identified hydrophobic stretches in leptin's A-B loop (amino acids 39-42) and in
      the N-terminal end of LEPR's IGD (amino acids 325-328) that are predicted to
      participate in site III and to interact with each other in a beta-sheet-like
      configuration. To verify this hypothesis, we prepared and purified to homogeneity
      (as verified by SDS/PAGE, gel filtration and reverse-phase chromatography)
      several alanine muteins of amino acids 39-42 in human and ovine leptins. CD
      analyses revealed that those mutations hardly affect the secondary structure. All
      muteins acted as true antagonists, i.e. they bound LEPR with an affinity similar
      to the wild-type hormone, had no agonistic activity and specifically inhibited
      leptin action in several leptin-responsive in vitro bioassays. Alanine
      mutagenesis of LEPR's IGD (amino acids 325-328) drastically reduced its
      biological but not binding activity, indicating the importance of this region for
      interaction with leptin's site III. FRET (fluorescence resonance energy transfer)
      microscopy experiments have documented that the transient FRET signalling
      occurring upon exposure to leptin results not from binding of the ligand, but
      from ligand-induced oligomerization of LEPRs mediated by leptin's site III.

PMID- 15952939
TI  - Research methods in psychiatric treatment studies. Critique and proposals.

PMID- 15952940
TI  - Disease, deficit or denial? Models of poor insight in psychosis.
AB  - OBJECTIVE: To examine the evidence for the three kinds of aetiological model that
      dominate the current literature on poor insight in psychosis: clinical models,
      the neuropsychological model, and the psychological denial model. METHOD: Studies
      pertaining to one or more of these aetiological models were identified, reviewed
      and critically evaluated. RESULTS: There is little support for clinical models,
      partly because they lack testable hypotheses. Several studies reveal a positive
      relationship between insight and executive function, which may be related to
      frontal lobe dysfunction. However, the extent to which this relationship is
      specific and independent of general cognitive impairment remains unclear. There
      is tentative evidence to support the psychological denial model. Recent data
      combining the latter two approaches suggest that multiple factors contribute to
      poor insight. CONCLUSION: Integration of different aetiological models is
      necessary for a fuller understanding of insight in psychosis. Future research
      should assess multiple aetiological mechanisms in single investigations.

PMID- 15952941
TI  - Guideline adherence in medication management of psychotic disorders: an
      observational multisite hospital study.
AB  - OBJECTIVE: To evaluate guideline adherence in in-patient medication care of
      psychotic disorders. METHOD: A total of 508 persons with psychotic disorders were
      included in a naturalistic multisite hospital study. Subjects were assessed
      weekly on mental state, social functioning, socioeconomic factors and medication
      prescriptions. RESULTS: In total, 17% of individuals were prescribed
      antipsychotic dosages above the recommended value. Among those with persistent
      psychotic symptoms, 73% received insufficient antipsychotic drug management.
      About 58% of patients with depressive symptoms were not treated according to
      guidelines, and 53% of patients did not receive adequate management of side
      effects from antipsychotic medications. Subjects with more than six previous
      psychiatric hospitalizations (OR 1.80, CI: 1.05-3.08) and those with a prominent
      thought disorder (OR 2.28, CI: 1.23-4.23) had a higher likelihood of not being
      treated according to guidelines. CONCLUSION: Individuals with chronic and thought
      disordered psychosis may be at a higher risk of receiving medication care not
      supported by guidelines.

PMID- 15952942
TI  - Breastfeeding and risk of schizophrenia in the Copenhagen Perinatal Cohort.
AB  - OBJECTIVE: The aim was to study whether early weaning from breastfeeding may be
      associated with increased risk of schizophrenia. METHOD: The current sample
      comprises 6841 individuals from the Copenhagen Perinatal Cohort of whom 1671
      (24%) had been breastfed for 2 weeks or less (early weaning) and 5170 (76%) had
      been breastfed longer. Maternal schizophrenia, parental social status, single
      mother status and gender were included as covariates in a multiple regression
      analysis of the effect of early weaning on the risk of hospitalization with
      schizophrenia. RESULTS: The sample comprised 93 cases of schizophrenia (1.4%).
      Maternal schizophrenia was the strongest risk factor and a significant
      association between single mother status and elevated offspring risk of
      schizophrenia was also observed. Early weaning was significantly related to later
      schizophrenia in both unadjusted and adjusted analyses (adjusted odds ratio 1.73
      with 95% CI: 1.13-2.67). CONCLUSION: No or <2 weeks of breastfeeding was
      associated with elevated risk of schizophrenia. The hypothesis of some protective
      effect of breastfeeding against the risk of later schizophrenia is supported by
      our data.

PMID- 15952943
TI  - Premorbid adjustment in first episode schizophrenia and schizoaffective
      disorders: a comparison of social and academic domains.
AB  - OBJECTIVE: Recent evidence suggests that premorbid adjustment in schizophrenia
      and related disorders can be separated into social and academic domains. In this
      paper, we examine the correlates of and prognostic significance of social and
      academic premorbid adjustment in a sample of 113 patients. METHOD: Premorbid
      adjustment, symptoms and cognitive functioning were assessed at presentation for
      treatment and symptoms were re-assessed after a year of treatment. RESULTS:
      Females and those with a diagnosis of schizoaffective disorder were found to have
      better premorbid adjustment in the academic domain, but not in the social domain.
      Neurocognitive functioning was more consistently related to academic than social
      adjustment. Better social and academic premorbid adjustment was correlated with
      lower negative symptoms after 1 year of treatment, but neither was a significant
      predictor of positive symptoms. CONCLUSION: Social and academic premorbid
      adjustments show different relations to gender, specific diagnosis and
      neurocognitive functioning in schizophrenia and related disorders.

PMID- 15952944
TI  - Patterns of premorbid functioning in first episode psychosis: relationship to 2
      year outcome.
AB  - OBJECTIVE: To determine how different patterns of premorbid functioning relate to
      outcome longitudinally. METHOD: Premorbid adjustment was assessed in 194 first
      episode of psychosis subjects. Positive and negative symptoms, depression,
      substance misuse and social and cognitive functioning were assessed over 2 years.
      RESULTS: Four patterns of premorbid adjustment: stable-good, stable-intermediate,
      poor-deteriorating and deteriorating were identified. Relative to the stable-good
      group, the deteriorating and poor-deteriorating groups had significantly more
      positive symptoms at 1-year follow-up but not at 2-year follow-up and
      significantly more negative symptoms and significantly poorer social functioning
      at both 1 and 2-years. Only verbal fluency and memory differentiated between the
      groups with the stable-good group having a superior performance. CONCLUSION:
      Those who demonstrated poor or deteriorating functioning prior to the onset of
      acute psychosis have a poorer outcome up to at least 2 years in terms of negative
      symptoms and social functioning.

PMID- 15952945
TI  - Are sociodemographic factors and year of delivery associated with hospital
      admission for postpartum psychosis? A study of 500,000 first-time mothers.
AB  - OBJECTIVE: To examine the association between first hospital admissions due to
      postpartum psychosis and the explanatory variables age, educational level,
      marital status and year of delivery. METHOD: All Swedish first-time mothers (n =
      502,767) were included during a 12-year period and followed for first hospital
      admissions due to postpartum psychosis. Cox regression was used to estimate
      hazard ratios, adjusted for the explanatory variables. RESULTS: Older age and
      being a single mother implied an increased risk of first hospital admissions due
      to postpartum psychosis among first-time mothers. Educational level was not
      associated with first hospital admissions due to postpartum psychosis. During the
      1990s, when a reduction in psychiatric beds occurred, first hospital admissions
      due to postpartum psychosis decreased significantly. CONCLUSION: Certain
      sociodemographic factors are associated with first hospital admissions due to
      postpartum psychosis. Untreated postpartum psychosis due to fewer psychiatric
      beds could have hazardous effects on mothers and their children.

PMID- 15952946
TI  - Cost of care of schizophrenia: a study of Indian out-patient attenders.
AB  - OBJECTIVE: To assess the cost of care of Indian out-patients with schizophrenia.
      METHOD: Cost of illness in 50 out-patients with schizophrenia was assessed over a
      6-month period together with structured assessments of psychopathology and
      disability, and compared with 50 out-patients with diabetes mellitus. RESULTS:
      Total annual costs of care of schizophrenia were 274 US dollars; these were not
      significantly different from diabetes mellitus. Indirect costs (63%) were higher
      than direct costs. Drug costs were high. The main brunt of financial burden was
      borne by the family. Total treatment costs in schizophrenia were significantly
      higher in those who were unemployed, those who visited the hospital more often,
      and were more severely ill and disabled. CONCLUSION: Schizophrenia is an
      expensive illness to treat even in developing countries. Costs of care are
      similar to those of chronic physical illness, such as diabetes mellitus. Costs
      are higher in severely ill and disabled patients.

PMID- 15952947
TI  - Metacognition amidst narratives of self and illness in schizophrenia:
      associations with neurocognition, symptoms, insight and quality of life.
AB  - OBJECTIVE: Impairments in laboratory tasks of metacognition appear to be
      associated with symptoms, functioning, and neurocognition in schizophrenia. We
      sought to replicate these results in a study of metacognition within personal
      narratives of self and illness. METHOD: Narratives of 61 men with schizophrenia
      were rated using the Metacognition Assessment Scale and correlated with
      concurrent assessment of symptoms, quality of life, neurocognition and insight.
      RESULTS: Controlling for age and education, understanding of one's own mind was
      linked with better neurocognition across multiple domains, and lesser emotional
      withdrawal. Greater understanding of other's mind was linked with better verbal
      memory and less emotional withdrawal. Greater metacognition in the context of
      purposeful problem solving was associated with better verbal memory, insight and
      social function, and less emotional withdrawal and paranoia. CONCLUSION: Deficits
      in metacognition within the narratives of persons with schizophrenia are linked
      with symptoms, quality of life, neurocognition and poorer awareness of illness.

PMID- 15952948
TI  - Research reports on treatments for bipolar disorder: preliminary assessment of
      methodological quality.
AB  - OBJECTIVE: To assess frequencies of types of publications about bipolar disorder
      (BD) and evaluate methodological quality of treatment studies. METHOD: We
      classified 100 randomly selected articles (1998-2002) from five psychiatric
      journals with highest impact ratings, by topic areas, and assessed methods
      employed in treatment studies. RESULTS: Topics ranked: treatment (41%; 37% on
      pharmacotherapy) > biology (31%) > psychopathology (14%) = miscellaneous (14%).
      Of treatment studies, only 19% of original articles were randomized, 15% were
      relatively large (n > or = 50) but non-randomized, 65% were small non-randomized,
      case-series or -reports, and 53% relied on baseline-to-endpoint contrasts without
      a control group. Patient dropout rates were > or =40% in 43% of prospective
      studies. Only two reports provided confidence intervals; one included a power
      analysis, and 53% included no references on study design or statistical methods.
      CONCLUSION: Even in highly respected journals, the typical methodological quality
      of recent reports on therapeutics for BD was unexpectedly limited, and
      psychopathology and psychotherapies were little studied.

PMID- 15952949
TI  - Body weight gain induced by a newer antipsychotic agent reversed as negative
      symptoms improved.
AB  - OBJECTIVE: We describe a patient in whom improvement in negative symptoms
      contributed to early weight loss and subsequent long-term improvement in weight
      management. METHOD: Case report. RESULTS: A 26-year-old woman with schizophrenia
      gained 7 kg over the course of 1 year after starting treatment with olanzapine.
      However, as negative symptoms gradually improved with treatment, she became
      motivated to diet and exercise regularly. She quickly lost 9 kg and subsequently
      maintained optimal weight (55 kg; body mass index, 24.1 kg/m(2) ). CONCLUSION:
      Important strategies for minimizing weight gain in patients taking antipsychotic
      agents include improving negative symptoms of avolition and apathy, regular
      monitoring of body weight and potential medical consequences of overweight and
      obesity, and educating the patient about the importance of diet and regular
      exercise.

PMID- 15952950
TI  - Invited comment.

PMID- 15952952
TI  - Excellent review of psychotropic drug-induced torsade de pointes.

PMID- 15952953
TI  - The highest intentional ziprasidone overdose was not fatal.

PMID- 15952956
TI  - Biographies.

PMID- 15952957
TI  - Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for the
      management of patients with bipolar disorder: consensus and controversies.
AB  - Since the previous publication of Canadian Network for Mood and Anxiety
      Treatments (CANMAT) guidelines in 1997, there has been a substantial increase in
      evidence-based treatment options for bipolar disorder. The present guidelines
      review the new evidence and use criteria to rate strength of evidence and
      incorporate effectiveness, safety, and tolerability data to determine global
      clinical recommendations for treatment of various phases of bipolar disorder. The
      guidelines suggest that although pharmacotherapy forms the cornerstone of
      management, utilization of adjunctive psychosocial treatments and incorporation
      of chronic disease management model involving a healthcare team are required in
      providing optimal management for patients with bipolar disorder. Lithium,
      valproate and several atypical antipsychotics are first-line treatments for acute
      mania. Bipolar depression and mixed states are frequently associated with
      suicidal acts; therefore assessment for suicide should always be an integral part
      of managing any bipolar patient. Lithium, lamotrigine or various combinations of
      antidepressant and mood-stabilizing agents are first-line treatments for bipolar
      depression. First-line options in the maintenance treatment of bipolar disorder
      are lithium, lamotrigine, valproate and olanzapine. Historical and symptom
      profiles help with treatment selection. With the growing recognition of bipolar
      II disorders, it is anticipated that a larger body of evidence will become
      available to guide treatment of this common and disabling condition. These
      guidelines also discuss issues related to bipolar disorder in women and those
      with comorbidity and include a section on safety and monitoring.

PMID- 15952958
TI  - A US perspective of the CANMAT bipolar guidelines.

PMID- 15952959
TI  - A European perspective on the Canadian guidelines for bipolar disorder.

PMID- 15952960
TI  - CANMAT guidelines for bipolar disorder: commentary from the African perspective.

PMID- 15952961
TI  - Australasian commentary on CANMAT guidelines for treatment of bipolar disorder.

PMID- 15952963
TI  - Abstracts for the British Association of Dermatologists 85th Annual Meeting,
      Glasgow, United Kingdom, 5-8 July 2005.

PMID- 15952962
TI  - CANMAT guidelines for bipolar disorder: a commentary from South America.

PMID- 15952966
TI  - Hair loss with chemotherapy: at a loss over its management?
AB  - Alopecia is a common side effect of chemotherapy treatments for cancer; for some
      individuals this results in complete hair loss. The extent of this depends on
      many factors including the type or combination of drugs administered, and their
      doses. Further, it can in some cases be lessened through use of scalp cooling
      techniques. This method of reducing hair loss has been available since the 1970s.
      However, previous evidence suggests that nurses are apathetic about its use,
      which in turn might mean that patients are not always offered this intervention.
      This small exploratory study investigated perceptions held by nurses
      administering chemotherapy towards alopecia and its management through scalp
      cooling. It entailed completion of a survey questionnaire by 13 nurses that
      regularly administered intravenous chemotherapy. These data were then augmented
      by those attained from follow-up, semi-structured interviews that were conducted
      with three of the sample. It determined that perceptions of scalp cooling were
      influenced by individuals' subjective notions of its efficacy constructed from
      their experiences of having administered scalp cooling. Furthermore, attempts to
      prevent hair loss were mediated by their cognitions of the experience of hair
      loss itself. This study determined that views held about scalp cooling varied
      considerably, and that it was unlikely to be offered to all suitable patients or
      administered in a systematic manner. Such variation in provision has implications
      both for patients wishing to access this treatment and for nurses wishing to
      audit its use and efficacy.

PMID- 15952965
TI  - Mapping the quality of life and unmet needs of urban women with metastatic breast
      cancer.
AB  - Enhancing quality of life and reducing the unmet needs of women are central to
      the successful management of advanced breast cancer. The objective of this study
      was to investigate the quality of life and support and information needs of urban
      women with advanced breast cancer. This study was conducted at four large urban
      hospitals in Melbourne, Australia. A consecutive sample of 105 women with
      advanced breast cancer completed a questionnaire that contained the European
      Organization of Research and Treatment of Cancer Quality of Life Q-C30 and the
      Supportive Care Needs Survey. Between one quarter and a third of the women
      reported difficulties with their physical, role and social functioning, and a
      little over a quarter of the women reported poor global health status. Fatigue
      was a problem for most women. The highest unmet needs were in the psychological
      and health information domains. Almost no differences in unmet needs were
      detected when comparing different demographic and disease characteristics of
      women. Health care providers should routinely monitor the quality of life and
      needs of women with advanced breast cancer to ensure that appropriate treatment,
      information or supportive services are made available.

PMID- 15952967
TI  - An evaluation of the domiciliary occupational therapy service in palliative
      cancer care in a community trust: a patient and carers perspective.
AB  - In the past 20 years there has been considerable growth in the provision of
      palliative care services. The shift in emphasis from hospice and hospital care to
      the development of community services has been significant. This enables people
      to be cared for at home and is in keeping with Government agenda. While this may
      be beneficial for the patient and fit in with the wishes of the family, it is
      likely to put heavy demands on the coping resources of individual carers. The
      views of service users are of paramount importance when discussing service
      evaluation and patient, family and carer empowerment. This research presents the
      findings of an evaluation of the domiciliary occupational therapy service
      provided for patients in the palliative stage of cancer care in North and West
      Belfast from the perspective of the patients and carers. For the purpose of this
      study, the palliative stage of cancer care is defined as the point from which the
      patient is no longer responsive to curative treatment, until death. A sample of
      30 patients and their primary informal carers were selected using purposive
      sampling. A structured interview was carried out with both the patients and their
      carers to obtain views. Results suggest that although both patients and their
      carers value the service provided and report high levels of satisfaction, there
      are gaps identified in service provision and a lack of clear information among
      patients and their carers about the role of the occupational therapist and the
      range of services they can provide. There is a need to build upon the good work
      being done by domiciliary occupational therapists in the area of palliative
      cancer care and increase education and resources to ensure that a patient
      centred, holistic, approach to care is used, addressing both the needs of the
      patient and their carers.

PMID- 15952968
TI  - Managing diabetes mellitus in patients with advanced cancer: a case note audit
      and guidelines.
AB  - Patients with advanced cancer and diabetes mellitus present a challenge to
      healthcare professionals. To establish how diabetes is currently being managed in
      these patients, we audited the care of patients who died in Cheltenham General
      Hospital over the previous 12 months with diagnoses of both diabetes mellitus and
      cancer. Management and monitoring of the diabetes was variable and there was
      little record of discussion between healthcare professionals and the patient or
      family regarding the diabetes. Thirty-two out of 42 patients continued to have
      blood sugar monitoring up to and including the day they died. We review the
      literature on this topic and suggest guidelines to help professionals to
      appropriately manage diabetes in the palliative setting at the end of life.

PMID- 15952969
TI  - The experience of making treatment decisions for women with early stage breast
      cancer: a diagrammatic representation.
AB  - Women who are making decisions about treatment for early stage breast cancer
      interact with a number of people when they are considering their treatment
      options and the impact breast cancer will have on their lives. Previous research
      has considered patient preferences for involvement in treatment decision-making
      and proposed factors that may influence breast cancer treatment decisions.
      However, to date, there has been a paucity of research focusing on the experience
      of making treatment decisions from the women's perspective. The aim of this paper
      is to describe the relationships between the women, the medical practitioners and
      other people, and to consider features that may be influential in the experience
      of making treatment decisions. Two models are proposed to represent concepts that
      are linked to the experience of making treatment decisions. The first model
      proposed has been formulated to represent factors that may influence the
      treatment decision. The second model highlights aspects of the women's lives that
      may be affected. This paper discusses concepts that are presented in the
      conceptual models and makes suggestions for future studies relating to the
      experience of making treatment decisions for women with breast cancer.

PMID- 15952970
TI  - Caring for patients with cancer in non-specialist wards: the nurse experience.
AB  - This study aims to describe the experiences of nurses caring for cancer patients
      in non-specialist wards. The study was conducted in a large (420 beds) and small
      (32 beds) hospital in an area health service with urban and rural populations in
      the west of Sydney. A qualitative descriptive approach was utilized to collect
      data from the nurses. Data were collected using a survey and in-depth interviews
      of nurses working in non-specialist cancer wards. Transcribed data were managed
      with Nudist Vivo software and analysed for common themes using process of
      constant comparison and contrast. Twenty-five surveys were returned and five
      nurses volunteered to be interviewed. The six major themes that emerged from
      analysis of data were: emotional nature of care, lack of time, lack of knowledge
      of cancer treatment, family support, environment not conducive to proper care and
      dealing with patient's non-acceptance of cancer diagnosis. The nurses in this
      study wished to provide quality supportive care for cancer patients and their
      families but the inconducive environment and inadequate relevant training
      hindered the nurses' efforts. This then presents further need of relevant
      training for nurses in cancer care and time management, to meet up with these
      challenges.

PMID- 15952971
TI  - Gastrointestinal and cutaneous AIDS-related Kaposi's sarcoma: different activity
      of liposomal doxorubicin according to location of lesions.
AB  - Kaposi's sarcoma (KS) continues to be a frequent neoplasm in third world AIDS
      patients. We carried out a prospective study to evaluate the effectiveness of
      liposomal doxorubicin (LD) in gastrointestinal KS patients as well as its
      differential clinical activity depending on the location of the lesions. The
      study included 15 male AIDS patients aged between 25 and 35 years (mean: 27
      years) with more than 25 cutaneous lesions and extensive gastrointestinal KS.
      They were treated with LD, 20 mg/m(2) every 21 days, for six cycles. Eleven (73%)
      of the patients obtained a complete response of the gastrointestinal KS lesions
      and four (27%) a partial response. Regarding cutaneous lesions, only two (13%) of
      the patients reached a complete response, six (40%) a partial response and seven
      (47%) stabilized their disease. By applying Fisher's test we found a significant
      difference (P < 0.00035) when comparing the effectiveness of LD in
      gastrointestinal lesions in relation to cutaneous lesions. We conclude that LD is
      more effective in gastrointestinal KS and can be recommended in patients in third
      world countries with extensive gastrointestinal lesions.

PMID- 15952972
TI  - Multiple cutaneous acral metastases in a woman with breast adenocarcinoma treated
      with pegylated liposomal doxorubicin: incidental or aetiological association?
AB  - This paper reports the case of a 45-year-old female with histologically
      documented, multiple cutaneous metastases in the palmar and plantar surface of
      the fingers and toes originating from a breast adenocarcinoma after treatment
      with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such
      a metastatic pattern from breast cancer and the eventual association with the
      chemotherapy administered are thoroughly discussed.

PMID- 15952973
TI  - Too much, too soon? Patients and health professionals' views concerning the
      impact of genetic testing at the time of breast cancer diagnosis in women under
      the age of 40.
AB  - Recent research suggests that women who develop breast cancer between the ages of
      30-34 may have specific tumour characteristics: Those with high grade, oestrogen
      receptor negative, human epidermal growth factor receptor 2 (HER-2) negative
      tumours have between a 10% and 27% chance of being a BRCA1 gene carrier. Carriers
      of BRCA1 and BRCA2 mutations have an increased risk of contralateral breast
      cancer and cancer of the ovary. Furthermore, recent research indicates that
      prophylactic mastectomy and/or oophorectomy offer a significant risk reduction in
      the development of breast/ovarian cancer. In the near future, women in the UK may
      be offered the choice of a genetic test close to the time of diagnosis. This
      timing not only provides additional dimensions to treatment decisions, but has
      psycho-social and familial implications as well. This exploratory study
      investigates, first, whether or not women diagnosed with breast cancer under the
      age of 40 would want to be offered information about genetic testing close to the
      time of their diagnosis. Then secondly, it explores whether the health care
      professionals treating them support this idea. Third, it highlights the reasons
      for the women and the health professionals perspectives and concerns. We held
      focus groups of 13 women who had their only, or first, breast cancer under the
      age of 40 and who were subsequently identified as BRCA1 or BRCA2 mutation
      carriers, asking them how they felt about this timing. We also interviewed 17
      health care professionals involved in various aspect of breast cancer care and
      cancer genetics. The majority of former breast cancer women and professionals
      believed that there was already emotional overload in coping with the cancer
      diagnosis and decisions regarding existing cancer treatment options and that
      offering genetic testing would add too much additional stress. Some members of
      both groups, however, thought that offering genetic testing around the time of
      breast cancer diagnosis would be more important if the results could alter
      treatment decisions.

PMID- 15952974
TI  - Provision of information for cancer patients: an appraisal and review.
AB  - This article is based on an appraisal of Cancer Information and Support Services
      in Britain supported by the UK-based charity Macmillan Cancer Relief.
      Commissioned in 2002, the appraisal formed part of a wider review aimed at
      extending knowledge about Cancer Information and Support Services. It was also
      designed to ensure that the Macmillan Cancer Information and Support Service
      Model continues to reflect the needs of people whose lives are affected by
      cancer. The individual services reviewed for the appraisal vary widely in terms
      of resources, staffing and organizational structure, but many common themes
      emerge. The importance of outreach and networking are highlighted, along with the
      problem of isolation. Many post-holders saw a need to include a hospital base,
      while the role played by volunteers is widely acknowledged. A key aim of the
      review was to start to identify the factors that contribute to the success of a
      service, and a number of these emerge from the study. The creation of a culture
      that enables such a service to thrive appears to be as important as securing
      financial and other resources. The contribution made by Macmillan is explored,
      and ways in which the organization can support the dissemination of knowledge are
      put forward.

PMID- 15952980
TI  - Living with Marfan syndrome: coping with stigma.
AB  - Social stigmatization can disrupt the ability of individuals with genetic
      conditions to successfully adapt to their situation. We offer data on perceptions
      of stigma from a cross-sectional survey of 174 adults with Marfan syndrome by
      self-report. Fifty-six respondents (32%) reported feeling discriminated against
      or socially devalued because of having Marfan syndrome. Endorsement of
      discrimination was significantly correlated with having depressive symptoms, low
      self-esteem, the view Marfan syndrome has had significant negative consequences
      on one's life, striae, and perceptions of workplace discrimination. Nearly 30% of
      respondents reported withdrawing from social situations that they anticipated
      would lead to feeling stigmatized, and 25% reported electing to keep their
      condition secret in potentially stigmatizing situations. Over 50% of respondents
      reported educating others about Marfan syndrome as a means of coping with their
      feelings of stigma, and endorsement of education was correlated with viewing
      involvement in the National Marfan Foundation as important. Instances of
      workplace discrimination were perceived by 20% of respondents, and 23% reported
      that they remained in a dissatisfying job due to having Marfan syndrome. Genetics
      professionals should actively engage patients with Marfan syndrome in discussions
      about social stigmatization and encourage use of coping strategies aimed at
      enhancing quality of life.

PMID- 15952981
TI  - Simultaneous identification of chromosomes 18, X and Y in uncultured amniocytes
      by using multi-primed in situ labelling technique.
AB  - The aim of this study is to validate the multi-PRINS (primed in situ labelling)
      technique for simultaneous detection of chromosomes 18, X and Y in uncultured
      amniocytes for prenatal diagnosis of aneuploidy. The sites of the newly
      synthesized DNA sequences were showed as fluorescent signals by using
      immunochemistry. A multi-PRINS technique was specifically performed for
      simultaneous detection in the same cells of three chromosome targets, e.g.
      chromosomes 18, X and Y. Fluorescent signals corresponding to chromosomes 18, X
      and Y were showed as yellow, red and green colour spots, respectively. A multi
      FISH technique using chromosome 18, X and Y probes was performed for comparison.
      Sixty cases were analysed using both multi-PRINS and multi-FISH. Fifty to two
      hundred nuclei were scored for each case for each technique. In all cases, there
      was no significant difference in the detection of chromosomes 18, X and Y
      regarding the sensitivity, the specificity and the efficiency; multi-PRINS and
      multi-FISH yield a similar distribution of the number of spots per nucleus. Both
      techniques were able to identify aneuploid cases without any ambiguity. Both
      multi-PRINS and multi-FISH can accurately and reliably detect aneuploidies
      involving chromosomes 18, X and Y in uncultured amniocytes. Finally, multi-PRINS
      represents a faster and more cost-effective alternative to FISH for prenatal
      testing of aneuploidy in uncultured amniocytes.

PMID- 15952982
TI  - Detection of hemizygosity in Hermansky-Pudlak syndrome by quantitative real-time
      PCR.
AB  - Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized
      by oculocutaneous albinism, a bleeding diathesis and, in some patients, pulmonary
      fibrosis or granulomatous colitis. HPS is associated with biosynthesis defects of
      melanosomes, platelet-dense bodies, and lysosomes. There are seven genetic HPS
      subtypes; HPS-1 is the most common. We used a real-time quantitative PCR (qPCR)
      approach to investigate six HPS-1 patients, previously assigned as having
      homozygous mutations in the HPS1 gene. HPS1 gene copy numbers, calculated by use
      of a comparative Ct method, revealed that one patient was in fact hemizygous for
      her c.1189delC (S396delC) HPS1 mutation. The causative deletion/insertion was
      13,966 bp in size, with defined breakpoints, and involved an adjacent gene
      (C10orf33). A mechanism of formation is proposed for the deletion/insertion, and
      both multiplex and qPCR indicated that the deletion/insertion was present in the
      patient, her brother, and her father. qPCR amplification is valuable for
      detecting deletions too small to be identified by fluorescence in situ
      hybridization. This demonstration of hemizygosity, performed using genomic DNA,
      can eliminate concerns about non-paternity and can verify the diagnosis of an
      autosomal recessive disorder when a DNA alteration appears to be homozygous by
      standard PCR and sequencing methods, and its pathogenicity is in doubt.

PMID- 15952983
TI  - LMNA mutation position predicts organ system involvement in laminopathies.
AB  - The underlying disease mechanisms likely include mutation effects on the nuclear
      envelope and on interactions between lamins and transcription factors. At the
      same time, can a simple genomic attribute -- for instance, mutation position
      within the LMNA sequence -- predict the complex phenotypic effects? In order to
      assess this, hierarchical cluster analysis (HCA) was used for assembling 16
      laminopathies into two classes based on organ system involvement. Ninety-one
      reported causative LMNA mutations in these laminopathies were then classified
      according to their position upstream or downstream of the nuclear localization
      signal sequence (NLS). Contingency analysis was used in order to assess a non
      random relationship between HCA laminopathy class and LMNA mutation position
      relative to the NLS. HCA laminopathy class and LMNA mutation position were
      strongly associated (p < 0.0001). The odds ratio for general association between
      an HCA class 1 laminopathy and a mutation upstream of the NLS sequence was 8.4
      (95% confidence interval = 2.9 - 24.7, p < 0.0001). Although the underlying
      molecular biology is complex, the findings support the hypothesis that
      laminopathy phenotype and LMNA genotype are non-randomly associated. Furthermore,
      HCA may be a tool to help with the study of phenotype - genotype associations, or
      'phenomics'.

PMID- 15952984
TI  - Inhibin A is a maternal serum marker for Down's syndrome early in the first
      trimester.
AB  - Inhibin A is a maternal serum marker for fetal Down's syndrome (DS) in the second
      trimester. We examined whether inhibin A could be used early in the first
      trimester. Maternal serum concentrations of inhibin A were determined in 81
      controls and 27 cases of fetal trisomy 21 in gestational week 5-11. The log MoM
      (Multiple of the Median of normal pregnancies) inhibin A concentration in DS
      pregnancies increased with gestational age (p = 0.001) from a mean log MoM
      (standard deviation) of -0.1754 (0.3712) (n = 11) in week 7-8 to a mean log MoM
      (standard deviation) of 0.1842 (0.2145) (n = 12) in week 9-11. This corresponded
      to an increase in inhibin median MoM from 0.67 to 1.53. When inhibin A was used
      together with pregnancy-associated plasma protein-A, free beta-human chorionic
      gonadotrophin and nuchal translucency as DS markers, the estimated detection
      rates were 81.4 and 82.6% in weeks 7-8 and 9-11, respectively, for false-positive
      rates of 0.9 and 1.0%. The performance of the latter combination early in the
      first trimester is nearly as good as that of integrated first- and second
      trimester screening, with the further advantage that the risk can be reported to
      the pregnant woman in first trimester.

PMID- 15952985
TI  - Chromosomal changes in prostate cancer: a fluorescence in situ hybridization
      study.
AB  - The incidence of prostate cancer (PC) is increasing steadily with the aging
      population in Singapore. As the pattern of chromosomal aberrations in Asian men
      with PC is poorly understood, we investigated the numerical aberrations for
      chromosomes 7, 8, 11, and 17 by fluorescence in situ hybridization (FISH). FISH
      was performed on standard sections and tissue microarrays of 54 PC and 33 benign
      prostatic hyperplasia (BPH) specimens. Among the 54 PC specimens, FISH detected
      44 cases as aneusomy and two as disomy and was unsuccessful for eight cases.
      Cytogenetic alterations of two or more chromosomes per tumor were detected in
      33/46 (72%) PCs. The most frequent alteration was aneusomy of chromosome 8
      detected in 34/46 (74%) cases followed by numerical aberrations in chromosome 7
      (61%). Gain of 8q24, loss of chromosome 7, and gain of 11q13 were associated with
      higher Gleason score and were statistically significant. Gain of chromosome 7 was
      more common in locally advanced disease, while gain of chromosome 11q13 and
      chromosome 7 was more common in metastatic disease.

PMID- 15952986
TI  - Molecular and phenotypic characteristics of metachromatic leukodystrophy patients
      from Poland.
AB  - The occurrence and genotype-phenotype correlations of the eight most common
      mutations in the arylsulfatase A (ARSA) gene were studied in 43 unrelated Polish
      patients suffering from different types of metachromatic leukodystrophy (MLD).
      Screening for mutations p.R84Q, p.S96F, c.459+1G>A, p.I179S, p.A212V,
      c.1204+1G>A, p.P426L, and c.1401-1411del allowed the identification of 53.5% of
      the mutant alleles. In the whole investigated group of patients, mutations
      c.459+1G>A and p.P426L were the most frequent, 19 and 17%, respectively. The
      prevalence of the third most frequent mutation, i.e. p.I179S (13%), seems to be
      higher than that in other populations. The incidence of c.1204+1G>A was 5%, which
      is higher than reported earlier (2%). It seems that p.I179S and c.1204+1G>A are
      more prevalent in MLD patients from Poland than from other countries. In the
      group examined by us, mutations p.R84Q, p.S96F, p.A212V, and c.1401-1411del were
      not detected; thus, 46.5% of MLD alleles remained unidentified. This indicates
      that other, novel or already described, but rare, mutations exist in Polish
      population. In late infantile homozygotes for c.459+1G>A and one homozygote for
      c.1204+1G>A, first clinical symptom was motor deterioration. In adult homozygotes
      for p.P426L, the disease onset manifested as gait disturbances, followed by
      choreoathetotic movements, difficulties in swallowing, dysarthria, tremor, and
      nystagmus. In the carriers of the p.I179S mutation, the hallmark of the clinical
      picture was psychotic disturbances.

PMID- 15952987
TI  - Is reduced CAG repeat length in androgen receptor gene associated with risk of
      prostate cancer in Indian population?
AB  - Shorter CAG repeats in androgen receptor (AR) gene have been found to be
      associated with an increased risk of prostate cancer (CaP). Ethnic variations in
      CAG repeat length may contribute to varying risks in different populations. To
      evaluate the prognostic significance of androgen receptor (AR) CAG repeats in
      Indian population for CaP, genomic DNA from 113 CaP, 57 benign prostate
      hyperplasia (BPH) patients and 133 normal healthy controls were examined by using
      a PCR-based GeneScan analysis. The mean number of CAG repeat in CaP was
      significantly lower as compared to the healthy controls (20.26 vs 22.98; p =
      0.016). The odds ratio for CaP was 2.96 (p < 0.01), when individuals with short
      CAG repeat (< or =22) were compared with those having longer repeats (>22). A
      significant association was also observed between short CAG repeat and young age
      at diagnosis (OR 2.18; p = 0.04). The mean CAG repeat was not significantly
      different in BPH and healthy controls; however, BPH patients showed a tendency
      towards short CAG repeats. Thus, our results show that CAG repeat polymorphism in
      AR gene is significantly associated with CaP risk, suggesting that AR CAG
      polymorphism may act as a risk modifier to CaP in Indian population.

PMID- 15952988
TI  - Mutation analysis of Wilson disease in the Spanish population -- identification
      of a prevalent substitution and eight novel mutations in the ATP7B gene.
AB  - Wilson disease (WD) is a copper metabolism disorder characterized by hepatic
      and/or neurological damage. More than 200 mutations in the ATP7B gene causing
      this autosomal recessive defect have been reported. In certain populations, a
      high prevalence of particular mutations allows rapid screening and diagnosis of
      the disease. We identified the ATP7B alterations in Spanish patients with WD.
      Mutations in the ATP7B gene were analysed in a total of 64 individuals from 40
      different WD families by PCR amplification, single-strand conformation
      polymorphism (SSCP) analysis and sequencing. Twenty-one different ATP7B gene
      mutations were identified, eight of which were novel. 74% of the disease alleles
      were characterized among the 40 unrelated probands. We identified a prevalent
      mutation in our population (Met645Arg), present in 55% of this 40 patients. The
      frequency of the remaining ATP7B alterations was low. In addition, 17 different
      polymorphic variants were found. There is remarkable allele heterogeneity in WD
      in the Spanish population. Nevertheless, SSCP screening for the most frequent
      mutations in our population is feasible and leads to the detection of about 74%
      of the mutated chromosomes. Molecular diagnosis of WD is very useful in clinical
      practice to confirm or support clinical suspicion.

PMID- 15952989
TI  - DNA sequence analysis for structure/function and mutation studies in Becker
      muscular dystrophy.
AB  - We systematically screened the whole coding region of 18 male muscular dystrophy
      patients whose clinical, histological and laboratory findings suggest Becker
      muscular dystrophy (present but abnormal dystrophin). No systematic mutation
      study of a cohort of patients with dystrophin of normal quality but abnormal
      quantity has been published. The complete coding sequence of the dystrophin gene
      (11 kb) of each patient was subjected to an automated sequence analysis by using
      muscle biopsy RNA; 535 bp of the gene promoter and 5'UTR were likewise sequenced.
      We identified seven disease-causing mutations (40%). Six were novel, including
      missense, nonsense, small deletion and splice site mutations. Sixty percent
      (11/18) of patients with decreased quantities of normal molecular weight
      dystrophin showed no mutation, but most of them had a family history highly
      suggestive of X-linked inheritance, suggesting transcription or translational
      deleterious affection, i.e. outside what was screened. Quantitative multiplex
      fluorescence polymerase chain studies of mutation-negative patients showed normal
      levels of dystrophin mRNA. In three patients, there was some reduction of the
      transcript suggesting a deleterious undetected gene change resulted in the
      reduction of RNA levels. Our data address important structure/function and
      genotype/phenotype correlations and it suggests that dystrophin protein studies
      must be interpreted with caution in deletion-negative male muscular dystrophy
      patients.

PMID- 15952990
TI  - Frequency of hereditary non-polyposis colorectal cancer among Uruguayan patients
      with colorectal cancer.
AB  - Few studies have investigated the frequency of hereditary non-polyposis
      colorectal cancer (HNPCC) in patients with colorectal cancer (CRC), and these
      have shown marked geographic variations. The aim of this study was to estimate
      the frequency of HNPCC in a cohort of Uruguayan CRC patients. We included all
      patients operated consecutively for CRC in the Hospital Central de las Fuerzas
      Armadas (Uruguay) between 1987 and 2003. Cases were classified into three groups:
      (i) those fulfilling Amsterdam criteria; (ii) those not fulfilling Amsterdam
      criteria but considered as a population at increased risk of cancer; and (iii)
      sporadic CRC. Genetic analysis to detect point mutations in hMLH/hMSH2/hMSH6
      genes was performed in group 1 patients. Cases not showing mutations were tested
      by multiplex ligation-dependent probe amplification. Among 461 patients, group 1
      represented 2.6%, group 2 represented 5.6%, and sporadic cases 91.8%.
      hMLH1/hMSH2/hMSH6 mutations were found in 25% of cases classified as HNPCC (two
      in hMLH1 and one in hMSH2). No mutations were detected in hMSH6 gene. The
      proportion of CRC patients that fulfilled Amsterdam criteria agrees with other
      reports. However, the percentage of HNPCC cases with identified mutations (25%)
      may be lower than that reported from other populations. This may reflect, among
      other possible causes, a different genetic profile in the Uruguayan population.

PMID- 15952991
TI  - A CFTR mutation (D1152H) in a family with mild lung disease and normal sweat
      chlorides.

PMID- 15952992
TI  - De novo alpha-actin mutations in monozygotic twins.

PMID- 15952993
TI  - Osteopenia and osteoporosis: previously unrecognized manifestations of Fabry
      disease.

PMID- 15952994
TI  - Cerebral and pulmonary nocardia in a bone marrow transplant patient.

PMID- 15952995
TI  - Heparin-induced skin necrosis.

PMID- 15952996
TI  - Susceptibility to infection in patients with neutropenia: the role of the innate
      immune system.
AB  - Chemotherapy-induced neutropenia increases the risk of infection. There appears
      to be a wide variability in the severity and length of infective episodes.
      Susceptibility to infections is determined by the underlying malignant disease
      and its treatment, environmental factors (e.g. nutritional state of the patient
      and hygiene) and genetically determined variations of the immune system. The
      majority of primary immunodeficiencies are rare (c. frequency one in 10 000),
      whereas some genetic polymorphisms in the innate immune system, such as profound
      mannose-binding lectin deficiency, are much more common (c. frequency one in 10).
      Here, we review the potential role of the innate immune system in determining
      susceptibility to infections in patients with neutropenia.

PMID- 15952997
TI  - Psychological complications in sickle cell disease.
AB  - This review examines the evidence for some of the common psychological
      complications found across the life span of patients with sickle cell disease
      (SCD), which are likely to be encountered by haematologists responsible for their
      medical management. Electronic searches of medical and psychological databases
      were conducted with a focus on three main areas: psychological coping, quality of
      life and neuropsychology. Psychological complications were identified in both
      children and adults with SCD, and included inappropriate pain coping strategies;
      reduced quality of life owing to restrictions in daily functioning, anxiety and
      depression; and neurocognitive impairment. There were wide variations in design
      and consistency of the studies, therefore, some caution needs to be observed in
      the findings. Moreover, interventional studies were lacking in some areas such as
      neuropsychology. Utilization of psychological interventions including patient
      education, cognitive behavioural therapy, and special educational support to help
      improve the quality of life of patients are recommended.

PMID- 15952998
TI  - Courting the expert: a clash of culture?
AB  - This article reviews the utility of expert opinion in legal proceedings and the
      deployment of expert witnesses in adversarial litigation. The use of expert
      witnesses to assist courts in making just and fair conclusions may be contrasted
      with the partisan interests of those who call them. An adversarial system is a
      bad method of scientific enquiry and undermines the court's capacity to reach the
      'right' answer. As a consequence, courts may reach the wrong conclusion based on
      bad science. The role of the expert as a witness places strain on an expert to
      provide certainty, where in fact there may be none. Recent reforms in the civil
      courts have changed little and the problem is even more acute in criminal trials.
      The expert can rely solely on the integrity of his or her own opinion, tempered
      with a little humility. However, when filtered through the rhetoric and advocacy
      of a court arena, even this may be compromised.

PMID- 15952999
TI  - Benefit of dexamethasone compared with prednisolone for childhood acute
      lymphoblastic leukaemia: results of the UK Medical Research Council ALL97
      randomized trial.
AB  - Corticosteroids are an essential component of treatment for acute lymphoblastic
      leukaemia (ALL). Prednisolone is the most commonly used steroid, particularly in
      the maintenance phase of therapy. There is increasing evidence that, even in
      equipotent dosage for glucocorticoid effect, dexamethasone has enhanced
      lymphoblast cytotoxicity and penetration of the central nervous system (CNS)
      compared with prednisolone. Substitution of dexamethasone for prednisolone in the
      treatment of ALL might, therefore, result in improved event-free and overall
      survival. Children with newly diagnosed ALL were randomly assigned to receive
      either dexamethasone or prednisolone in the induction, consolidation (all
      received dexamethasone in intensification) and continuation phases of treatment.
      Among 1603 eligible randomized patients, those receiving dexamethasone had half
      the risk of isolated CNS relapse (P = 0.0007). Event-free survival was
      significantly improved with dexamethasone (84.2% vs. 75.6% at 5 years; P = 0.01),
      with no evidence of differing effects in any subgroup of patients. The use of 6.5
      mg/m(2) dexamethasone throughout treatment for ALL led to a significant decrease
      in the risk of relapse for all risk-groups of patients and, despite the increased
      toxicity, should now be regarded as part of standard therapy for childhood ALL.

PMID- 15953000
TI  - LISA: a web-based decision-support system for trial management of childhood acute
      lymphoblastic leukaemia.
AB  - Continuation chemotherapy is a key component of the treatment of childhood acute
      lymphoblastic leukaemia. During this treatment phase, weekly dose adjustments are
      carried out based on current and historical full blood counts (FBCs). The dose
      decision pathway is complex and suboptimal therapy may result if information on
      FBC results is not readily available and/or the prescriber is inexperienced. A
      web-based decision-support system (Leukaemia Intervention Scheduling and Advice,
      'LISA') was designed to facilitate access to FBC information across geographical
      locations and to assist with dosage adjustments. A balanced-block crossover
      analysis was performed to evaluate the system. Thirty-six clinicians with varying
      degrees of experience were each asked to decide on appropriate oral chemotherapy
      dosages for eight simulated cases: four using LISA and four without. LISA
      significantly reduced the number of erroneous prescriptions (zero of 144 with
      LISA vs. 54 of 144 without; P < 0.0001) without affecting the number of times
      subjects deliberately overrode the protocol (seven of 144 times using LISA and
      six of 144 without). Using LISA reduced the time taken by novices to reach a
      decision for each case but increased the time taken by experts. Thirty-five of 36
      subjects said they would be likely to use the system if it were available. A
      system like LISA is likely to be acceptable to clinicians, and has the potential
      to increase protocol compliance and decrease prescribing errors while allowing
      clinicians to override the protocol in specific cases where sound reasons exist
      for doing so.

PMID- 15953001
TI  - PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for
      previously untreated patients with multiple myeloma.
AB  - Bortezomib (formerly PS-341) has significant activity in patients with relapsed
      multiple myeloma (MM), its efficacy is increased with the addition of
      dexamethasone and it demonstrates synergy with doxorubicin, thus providing the
      rationale for combination therapy with bortezomib, doxorubicin and dexamethasone
      (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising
      bortezomib 1.3 mg/m(2) on days 1, 4, 8 and 11, along with dexamethasone 40 mg on
      days 1-4, 8-11 and 15-18 during cycle 1 and days 1-4 during cycles 2-4. During
      days 1-4, patients also received 0, 4.5 or 9 mg/m(2) of doxorubicin at dose
      levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC)
      collection, patients received high-dose melphalan (MEL200) with PBSC
      transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%)
      achieved at least a partial response (PR), including complete response (CR) in
      five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received
      MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%,
      near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective,
      did not prejudice subsequent PBSC collection, and should be further evaluated in
      prospective randomized trials.

PMID- 15953002
TI  - Low-dose thalidomide in combination with oral weekly cyclophosphamide and pulsed
      dexamethasone is a well tolerated and effective regimen in patients with relapsed
      and refractory multiple myeloma.
AB  - The feasibility and efficacy of a triple regimen of oral weekly cyclophosphamide,
      monthly pulsed dexamethasone and low-dose Thalidomide (CDT) was studied in 52
      patients with relapsed or refractory multiple myeloma (MM). All 52 patients were
      evaluable for response with a median follow up of 18 (4-29) months. About 17%
      achieved complete response (CR), 62% partial response (PR), 11% minimal response
      (MR), 6% stable disease (SD) and 4% progressive disease (PD), resulting in an
      objective response rate (>/=MR) of 90%. Subsequent to successful response, nine
      patients received high-dose therapy (HDT) followed by stem cell transplantation
      (SCT) and 34 received thalidomide monotherapy as maintenance. Response rate was
      not influenced by disease status, prior HDT or age. The regimen was successfully
      delivered to all patients except for one patient who developed abnormal liver
      function at 7 weeks. Infective complications were minimal and there were no
      infection-related deaths. The estimated overall and event-free survival (EFS) at
      2 years was 73% and 34%, respectively, and the median time to progression has not
      been reached. We conclude that the CDT regimen is safe, well tolerated and
      effective in patients with relapsed and refractory myeloma.

PMID- 15953003
TI  - Efficacy and tolerability of danazol as a treatment for the anaemia of
      myelofibrosis with myeloid metaplasia: long-term results in 30 patients.
AB  - Androgens are considered the treatment of choice for the anaemia of myelofibrosis
      with myeloid metaplasia (MMM). Good results have been reported in a few patients
      treated with danazol, a synthetic attenuated androgen. The long-term efficacy and
      tolerability of danazol as treatment for the anaemia of MMM was evaluated in 30
      patients, who received 600 mg/d, with progressive tapering to the minimum
      effective dose in the responders after 6 months. Complete response (CR) was
      defined as transfusion cessation with normal Hb and partial response (PR) as an
      Hb increase >/=1.5 g/dl with transfusion-independent Hb values >10 g/dl
      maintained for at least 8 weeks. Median follow-up was 20.5 months (range: 3.5-58
      months). Response was achieved in 11 patients (37%), including eight CRs and
      three PRs. Median time to response was 5 months (range: 1-9 months). Four
      patients stopped responding at 6-24 months, two responders discontinued treatment
      because of toxicity, and five maintained response at 3.5-42 months. Pretreatment
      variables associated with response were lack of transfusion requirement (P=
      0.001) and higher Hb at treatment start (P= 0.02). Toxicity was usually moderate,
      leading to treatment withdrawal in only two cases. Danazol is effective and well
      tolerated in a substantial proportion of MMM patients with anaemia.

PMID- 15953004
TI  - Bortezomib therapy alone and in combination with dexamethasone for previously
      untreated symptomatic multiple myeloma.
AB  - Bortezomib, as a single agent and in combination with dexamethasone, was examined
      as first-line treatment in 32 consecutive patients with untreated symptomatic
      multiple myeloma. Patients received bortezomib 1.3 mg/m(2) for a maximum of six 3
      week cycles; oral dexamethasone 40 mg was added if a less than partial response
      (PR) was achieved after two cycles or a less than complete response (CR) was
      achieved after four cycles. The response rate (CR + PR) was 88%, with
      undetectable paraprotein (CR) in 6%, and detectable by immunofixation only in 19%
      [near (n)CR]. All 32 patients completed the first two cycles of bortezomib alone,
      of whom 3% achieved CR, 9% nCR, and 28% PR. Ten patients received single-agent
      bortezomib on study, and dexamethasone was added in 22, leading to 15 improved
      responses. The most common adverse events >/=grade 2 included sensory neuropathy
      (31%), constipation (28%), myalgia (28%) and fatigue (25%). Sensory neuropathy
      grade 2 or 3 was reversible within a median of 3 months in five of 10 patients.
      Bortezomib treatment did not affect stem cell mobilization in eight or
      transplantation in six patients. Bortezomib alone or in combination with
      dexamethasone is an effective induction therapy with a high CR and nCR rate and
      manageable toxicities in previously untreated patients with myeloma.

PMID- 15953005
TI  - Genetic analysis of the 2q33 region containing CD28-CTLA4-ICOS genes: association
      with non-Hodgkin's lymphoma.
AB  - There is strong evidence that altered immunological function entails an increased
      risk of lymphoma, although the current knowledge of aetiological factors for
      lymphomas is limited. The CTLA4 gene encodes a receptor that provides a negative
      signal to the T-cell once an immune response is initiated and completed. We
      analysed the 2q33 chromosomal region harbouring CD28, CTLA4 and ICOS genes, which
      are closely linked and have related functions in immune regulation, for
      association in 100 non-Hodgkin's lymphoma (NHL) patients and in 128 healthy
      controls; both groups originated from Sardinia. There was a strong association of
      the CTLA4 49A and the 3'-untranslated region (AT)(82) alleles with NHL [odds
      ratio (OR) = 2, 95% confidence interval (CI) = 1.2-3.2, and OR = 1.6, 95% CI =
      1.1-2.4 respectively]. CTLA4-318C:49A:(AT)(82) was the most represented haplotype
      in the studied population and was associated with NHL (P = 0.0029, OR = 1.76, 95%
      CI = 1.2-2.5). Strong linkage disequilibrium was detected between CD28, CTLA4 and
      ICOS and a 'common' haplotype was found very frequently among NHLs. However, no
      independent association between CD28, ICOS, D2S72 markers and NHL was observed.
      Our findings enable CTLA4 from adjacent functionally related genes as the true
      causative risk gene for NHL susceptibility at least in Sardinian patients.

PMID- 15953006
TI  - SHP1 expression in bone marrow biopsies of myelodysplastic syndrome patients: a
      new prognostic factor.
AB  - Myelodysplastic syndrome (MDS) progresses into acute leukaemia with a variable
      time course. We analysed 45 newly diagnosed patients and found that the
      expression of the Src homology 2 domain-containing tyrosine phosphatase 1 (SHP1)
      had a significant impact on disease severity, progression and overall prognosis.
      Global or lineage-specific loss of SHP1 was observed by immunohistochemistry in
      bone marrow biopsies of MDS patients who progressed rapidly (P = 0.0021) and had
      shorter survival (P < 0.001). Cox regression analysis demonstrated that SHP1
      expression in megakaryocytes had prognostic relevance for time to progression (P
      = 0.009) and overall survival (P = 0.001).

PMID- 15953007
TI  - Outcomes of patients with acute leukaemia who relapsed after reduced-intensity
      stem cell transplantation from HLA-identical or one antigen-mismatched related
      donors.
AB  - The characteristics of relapse following reduced-intensity stem-cell
      transplantation (RIST) remain to be clarified. We reviewed the medical records of
      19 patients with acute leukaemia [acute myeloid leukaemia (AML), 16; acute
      lymphoblastic leukaemia (ALL), 3] who relapsed after RIST from related donors
      using purine-analogue-based regimens. Their median age was 55 years (range, 29-65
      years). Median interval between RIST and relapse was 4.9 months (range, 1.8-24.9
      months). Three chose not to receive interventions. The remaining 16 patients
      received withdrawal of immunosuppression (n = 3), chemotherapy (n = 2), donor
      lymphocyte infusion (n = 10) and second transplantation (n = 7), alone (n = 9) or
      in combination (n = 7). Four are alive with a median follow-up of 27.6 months
      (range, 16.0-28.9 months); three in remission and one in relapse. The 2-year
      overall survival after relapse was 28.9%. Causes of death in 15 patients included
      progressive disease (n = 7), graft-versus-host disease (n = 5) and infections (n
      = 3). Cumulative incidences of relapse-related and non-relapse-related deaths at
      2 years after relapse were 37% and 32% respectively. Two prognostic factors were
      identified on univariate analysis: age [P = 0.017; hazard ratio (HR), 1.16; 95%
      confidence interval (CI), 1.03-1.32], and ALL as underlying disease (P = 0.011;
      HR, 10.4; 95% CI, 1.73-62.4). Some AML patients who relapse after RIST achieve
      durable remission with allogeneic immunotherapy-based interventions; however they
      carry a significant risk of non-relapse mortality.

PMID- 15953008
TI  - Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana
      Farber Cancer Institute protocols: effect of age and risk stratification of
      disease.
AB  - Children with acute lymphoblastic leukaemia (ALL) are at increased risk for
      thromboembolism (TE). Identification of a susceptible population is crucial for
      effective thromboprophylaxis. However, the risk factors for ALL-associated TE are
      unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to
      increase the incidence of TE. Dana-Farber Cancer Institute (DFCI)-ALL protocols
      use a combination of ASP and steroids during the postinduction intensification
      phase when high-risk (HR) patients receive thrice the steroid-dose given to
      standard-risk (SR) patients. We studied prospectively assembled cohorts of
      children treated on two consecutive DFCI-ALL protocols to define the risk factors
      for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight
      (seven HR) during intensification. Seven (44%) of 16 older patients (>/=10 years)
      compared with three of 75 (4%) younger patients developed TE (P < 0.0001). Nine
      of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0.0006). Gender,
      ALL-immunophenotype, steroid-type or ASP dosing schedule did not alter the risk
      but older age and HR-disease were factors predisposing to TE associated with DFCI
      ALL protocols. Age-related risk may partly reflect the effect of ALL-risk
      stratification. Higher dose steroids combined with ASP may lead to an increased
      risk of TE in HR patients.

PMID- 15953009
TI  - Incidence of thrombotic complications in patients with haematological
      malignancies with central venous catheters: a prospective multicentre study.
AB  - This prospective, observational and multicentre study assessed the incidence of,
      and risk factors for, symptomatic venous thrombotic complications after central
      venous catheter (CVC) positioning in patients with haematological malignancies. A
      total of 458 consecutive CVC insertions were registered in 416 patients (81.2% of
      whom had severe thrombocytopenia). Over the observation period (3 months or up to
      catheter removal), the incidence of events was: CVC-related deep vein thrombosis
      (DVT), 1.5%; lower limb DVT, 0.4%; pulmonary embolism (PE), 1.3%; fatal PE, 0.6%;
      CVC-related superficial thrombophlebitis, 3.9%; CVC-occlusion/malfunction of
      thrombotic origin, 6.1%; major arterial events, 1.1%. Severe bleeding and CVC
      related infections were observed in 3.5% and 4.6% of cases respectively. A
      composite end point (any venous thromboembolism or superficial thrombophlebitis
      or CVC occlusion/malfunction) was defined in order to consider venous thrombotic
      events with a significant impact on clinical practice. With this criterion, the
      overall incidence was 12.0% (2.54 cases/1000 catheter days). No factor helped to
      predict venous thrombotic complications: only thrombocytopenia was associated
      with a weak trend for a reduced risk (odds ratio 0.52; 95% confidence interval
      0.26-1.07). No severe bleeding was observed in those patients who received
      antithrombotic prophylaxis. This study shows that the impact on clinical practice
      of symptomatic CVC-related thrombotic complications is not negligible in patients
      with haematological malignancies.

PMID- 15953010
TI  - Hepatitis C virus-related thrombocytopenia: clinical and laboratory
      characteristics compared with chronic immune thrombocytopenic purpura.
AB  - Thrombocytopenia can be a complication of hepatitis C viral (HCV) infection.
      However, there is little published data regarding the clinical and laboratory
      manifestations of HCV-related thrombocytopenia (HCV-TP) compared with adult
      chronic immune thrombocytopenic purpura (CITP). We reviewed the medical records
      for all patients evaluated for chronic thrombocytopenia by the Haematology
      Service between January 1996 and June 2000. All patients were screened for HCV
      infection at the time of initial diagnosis. Of 250 patients who fulfilled
      American Society of Hematology criteria for CITP, 76 (30%) were HCV seropositive.
      HCV-TP patients were older [mean age (+/-SD) 54.9 +/- 8 years vs. 40.3 +/- 8
      years, P </= 0.001] and equally distributed between both sexes. HCV-TP patients
      had less severe thrombocytopenia, defined as platelet count </=10 x 10(9)/l (4%
      vs. 46% for CITP, P </= 0.001). However, 56 (74%) had a platelet count </=50 x
      10(9)/l. Symptoms and signs of thrombocytopenia were less frequent in HCV-TP, but
      major bleeding was more frequent (25% vs. 10%, P = 0.0059). Serum cryoglobulins
      and anticardiolipin antibodies were more frequent in HCV-TP (90% and 62%
      respectively), but rare in CITP (7% and 15%, P </= 0.001 compared with HCV-TP).
      HCV infection can be associated with significant thrombocytopenia and appears to
      be a distinct clinical entity.

PMID- 15953011
TI  - Genetic analysis in FXI deficiency: six novel mutations and the use of a
      polymerase chain reaction-based test to define a whole gene deletion.
AB  - The genetic basis of factor XI (FXI) deficiency was investigated in 30 patients
      from 13 different families of non-Jewish origin. Twelve different mutations were
      detected (including six novel changes), seven missense mutations and three
      mutations leading to null alleles. Haplotype analysis suggested a large gene
      deletion in one family. We confirmed the presence of a recently reported Alu
      mediated FXI gene deletion. An unrelated patient with severe deficiency was shown
      to be compound heterozygous for A412V and this whole gene deletion. We suggest
      that this recurrent gene deletion should be included in the genetic analysis of
      FXI deficiency.

PMID- 15953012
TI  - Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of
      complement blockade on the production of TNF-alpha and IL-10. Implications for
      the growth of malignant B-cell clones.
AB  - Monoclonal antibodies produced by patients with lymphoproliferative diseases
      sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly
      agglutinate and form immune complexes (IC) when cooled below normal body
      temperature or through variation in pH and ionic strength. In accordance with our
      findings of IC-induced cytokine production from peripheral blood mononuclear
      cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also
      induce cytokine production. One IgG and one IgM type I CG from two patients with
      multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified
      and added to PBMC cultures. In separate experiments temperature and ionic
      strength were varied, or FcgammaRIIa, FcgammaRIII and complement activation were
      blocked; supernatant cytokine levels were then determined by enzyme-linked
      immunosorbent assay. CG-induced cytokine production from monocytes varied with
      precipitation induced by changes in temperature and ionic strength and was
      mediated via FcgammaRIIa- and complement-dependent mechanisms. Complement
      blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that
      was inversely correlated with decreased production of tumour necrosis factor
      alpha. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in
      CG-associated lymphoproliferative diseases with constant complement consumption.
      Knowledge of mechanisms underlying CG-induced cytokine production can be useful
      for designing treatments for type I CG-associated pathology in
      lymphoproliferative diseases.

PMID- 15953013
TI  - Red cell pyruvate kinase deficiency: 17 new mutations of the PK-LR gene.
AB  - The PK-LR gene was studied in 23 patients with congenital haemolytic anaemia
      associated with erythrocyte pyruvate kinase (PK) deficiency. Twenty-seven
      different mutations were detected among the 42 mutated alleles identified: 19
      missense mutations, four splice site mutations and one nonsense, one single base
      deletion and two large deletions. Seventeen of them (107G, 278T, 403T, 409A,
      661A, 859C, 958A, 1094T, 1190T, 1209A, 1232C, 1369G, 507A, IVS9 -1c, IVS9 +43c
      [corrected] del C224, del 5006bp IVS3--> nt 1431) were new. Although all the
      exons, the flanking regions and the promoter were sequenced in all cases, we
      failed to detect the second expected mutation in four subjects. To correlate
      genotype to phenotype, the molecular results were related to the biochemical
      properties of the mutant enzymes by an analysis of the three-dimensional
      structure of erythrocyte PK. The new mutant 409A, found in association with the
      large deletion of 5006 bp in a newborn baby who died soon after birth, was
      functionally characterized by mutagenesis and in vitro expression of the protein
      to investigate its contribution in the severity of the clinical pattern. However,
      the biochemical data obtained for the mutant enzyme cannot explain the severe
      anaemia found in the PK-deficient patient hemizygous for this mutation.

PMID- 15953014
TI  - Recessive congenital methaemoglobinaemia: functional characterization of the
      novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase.
AB  - Type I recessive congenital methaemoglobinaemia (RCM), caused by the reduced form
      of nicotinamide adenine dinucleotide (NADH)-cytochrome b(5) reductase (cytb(5)r)
      deficiency, manifests clinically as cyanosis without neurological dysfunction.
      Two mutations, E255- and G291D, have been identified in the NADH-binding lobe of
      cytb(5)r in previously reported patients, and we have detected a further novel
      mutation, D239G, in this lobe in two unrelated Irish families. Although one
      family belongs to the genetically isolated Traveller Community, which separated
      from the general Irish population during the 1845-48 famine, the D239G mutation
      was present on the same haplotype in both families. Three known cytb(5)r
      mutations were also identified, including the R159- mutation, which causes loss
      of the entire NADH-binding lobe and had previously been reported in an individual
      with type II RCM. Characterization of the three NADH-binding lobe mutants using a
      heterologous expression system revealed that all three variants retained
      stoichiometric levels of flavin adenine dinucleotide with spectroscopic and
      thermodynamic properties comparable with those of native cytb(5)r. In contrast to
      the E255- and G291D variants, the novel D239G mutation had no adverse impact on
      protein thermostability. The D239G mutation perturbed substrate binding, causing
      both decreased specificity for NADH and increased specificity for NADPH. Thus
      cytb(5)r deficient patients who are heterozygous for an NADH-binding lobe
      mutation can exhibit the clinically less severe type I phenotype, even in
      association with heterozygous deletion of the NADH-binding lobe.

PMID- 15953019
TI  - Multidrug resistance in Gram-negative bacteria that produce extended-spectrum
      beta-lactamases (ESBLs).
AB  - In 1983, just two years after the introduction of the oxymino-beta-lactams to the
      market , the first extended-spectrum beta-lactamases were isolated in Germany
      from Klebsiella pneumoniae strains. Since then several outbreaks have been
      reported in many European countries and the USA, and nowadays in several places
      worldwide the problem seems to reach endemic dimensions, with rates exceeding 50%
      in some countries, such as Portugal and Turkey. On the other hand not only K.
      pneumoniae but also Escherichia coli strains, with Enterobacter aerogenes
      predominating among the other enterobacteriaceal species, are increasingly
      reported as ESBL producers. In this review types, molecular characteristics,
      detection methods, epidemiology as well as interventions for therapy and
      antibiotic strategies to prevent and control infections caused by ESBL-producing
      microorganisms, are presented and discussed.

PMID- 15953020
TI  - Treatment and control of severe infections caused by multiresistant Pseudomonas
      aeruginosa.
AB  - Pseudomonas aeruginosa is one of the leading causes of nosocomial infections.
      Severe infections, such as pneumonia or bacteraemia, are associated with high
      mortality rates and are often difficult to treat, as the repertoire of useful
      anti-pseudomonal agents is limited (some beta-lactams, fluoroquinolones and
      aminoglycosides, and the polymyxins as last-resort drugs); moreover, P.
      aeruginosa exhibits remarkable ability to acquire resistance to these agents.
      Acquired resistance arises by mutation or acquisition of exogenous resistance
      determinants and can be mediated by several mechanisms (degrading enzymes,
      reduced permeability, active efflux and target modification). Overall, resistance
      rates are on the increase, and may be different in different settings, so that
      surveillance of P. aeruginosa susceptibility is essential for the definition of
      empirical regimens. Multidrug resistance is frequent, and clinical isolates
      resistant to virtually all anti-pseudomonal agents are increasingly being
      reported. Monotherapy is usually recommended for uncomplicated urinary tract
      infections, while combination therapy is normally recommended for severe
      infections, such as bacteraemia and pneumonia, although, at least in some cases,
      the advantage of combination therapy remains a matter of debate. Antimicrobial
      use is a risk factor for P. aeruginosa resistance, especially with some agents
      (fluoroquinolones and carbapenems), and interventions based on antimicrobial
      rotation and restriction of certain agents can be useful to control the spread of
      resistance. Similar measures, together with the prudent use of antibiotics and
      compliance with infection control measures, are essential to preserve the
      efficacy of the currently available anti-pseudomonal agents, in view of the
      dearth, in the near future, of new options against multidrug-resistant P.
      aeruginosa strains.

PMID- 15953021
TI  - Vancomycin-resistant enterococci: consequences for therapy and infection control.
AB  - Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial
      pathogens, initially in the USA, but now also in Europe, where hospital outbreaks
      are being reported with increasing frequency, although the incidence of VRE
      infections remains extremely low in most European countries. The recently
      demonstrated in-human transmission of vancomycin resistance from VRE to
      methicillin-resistant Staphylococcus aureus (MRSA) in two American patients
      underscores the potential danger of a coexisting reservoir of both pathogens. As
      MRSA is already endemic in many European hospital settings, prevention of
      endemicity with VRE seems relevant, but should be balanced against the costs
      associated with the implementation of effective strategies. The presence of a
      large community reservoir of VRE in Europe could hamper the feasibility of
      infection control strategies. Although the prevalence of colonisation amongst
      healthy subjects has apparently decreased after the ban on avoparcin use in the
      agricultural industry, a large proportion of admitted patients are still
      potential sources of VRE transmission. With no risk profile available to identify
      these carriers, effective screening, followed by barrier precautions for
      carriers, seems to be impossible. Recent studies, however, have suggested that
      hospital outbreaks are almost exclusively caused by specific genogroups of VRE
      that can be characterised phenotypically and genotypically (e.g., co-resistance
      to ampicillin and the presence of the variant esp gene). Based on our own
      experience, we propose that VRE infection control programmes should be restricted
      to patients colonised with these VRE strains. If such a strain is cultured from a
      clinical sample, surveillance amongst contact patients is recommended and barrier
      precautions should be implemented in the case of documented spread.

PMID- 15953023
TI  - New concepts in Salmonella virulence: the importance of reducing the
      intracellular growth rate in the host.
AB  - The literature refers to Salmonella enterica as an intracellular bacterial
      pathogen that proliferates within vacuoles of mammalian cells. However, recent in
      vivo studies have revealed that the vast majority of infected cells contain very
      few intracellular bacteria (three to four organisms). Salmonella intracellular
      growth is also limited in cultured dendritic cells and fibroblasts, two cell
      types abundant in tissues located underneath the intestinal epithelium. Recently,
      a Salmonella factor previously known for its role as a negative regulator of
      intracellular growth has been shown to tightly repress certain pathogen functions
      upon host colonization and to be critical for virulence. The connection between
      virulence and the negative control of intracellular growth is further sustained
      by the fact that some attenuated mutants overgrow in non-phagocytic cells located
      in the intestinal lamina propria. These findings are changing our classical view
      of Salmonella as a fast growing intracellular pathogen and suggest that this
      pathogen may trigger responses directed to reduce the growth rate within the
      infected cell. These responses could play a critical role in modulating the
      delicate balance between disease and persistence.

PMID- 15953024
TI  - Helicobacter pylori-host cell interactions mediated by type IV secretion.
AB  - Helicobacter pylori is a human-specific gastric pathogen that colonizes over half
      the world's population. Infection with this bacterium is associated with a
      spectrum of gastric pathologies ranging from mild gastritis to peptic ulcers and
      gastric cancer. A strong predictor of severe disease outcome is infection with a
      bacterial strain harbouring the cag (cytotoxin associated gene) pathogenicity
      island (PAI), a 40 kb stretch of DNA that encodes homologues of several
      components of a type IV secretion system (TFSS). One gene within the cag PAI,
      cagA, has been shown to encode a substrate for the TFSS which is translocated
      into host cells and causes multiple changes in host cell signalling. Here we
      review recent advances in the characterization of type IV secretion, the
      activities of CagA and CagA-independent effects of the TFSS, which are
      contributing to our understanding of H. pylori pathogenesis.

PMID- 15953025
TI  - Cellular internalization of cytolethal distending toxin: a new end to a known
      pathway.
AB  - The cytolethal distending toxins (CDTs) are unique in their ability to induce DNA
      damage, activate checkpoint responses and cause cell cycle arrest or apoptosis in
      intoxicated cells. However, little is known about their cellular internalization
      pathway. We demonstrate that binding of the Haemophilus ducreyi CDT (HdCDT) on
      the plasma membrane of sensitive cells was abolished by cholesterol extraction
      with methyl-beta-cyclodextrin. The toxin was internalized via the Golgi complex,
      and retrogradely transported to the endoplasmic reticulum (ER), as assessed by N
      linked glycosylation. Further translocation from the ER did not require the ER
      associated degradation (ERAD) pathway, and was Derlin-1 independent. The
      genotoxic activity of HdCDT was dependent on its internalization and its DNase
      activity, as induction of DNA double-stranded breaks was prevented in Brefeldin A
      treated cells and in cells exposed to a catalytically inactive toxin. Our data
      contribute to a better understanding of the CDT mode of action and highlight two
      important aspects of the biology of this bacterial toxin family: (i) HdCDT
      translocation from the ER to the nucleus does not involve the classical pathways
      followed by other retrogradely transported toxins and (ii) toxin internalization
      is crucial for execution of its genotoxic activity.

PMID- 15953026
TI  - Colonization of the salivary glands of Naucoris cimicoides by Mycobacterium
      ulcerans requires host plasmatocytes and a macrolide toxin, mycolactone.
AB  - Mycobacterium ulcerans was first identified as the causative agent of Buruli
      ulcer; this cutaneous tissue-destructive process represents the third most
      important mycobacterial disease in humans after tuberculosis and leprosy. More
      recently other life traits were documented. M. ulcerans is mainly detected in
      humid tropical zones as part of a complex ecosystem comprising algae, aquatic
      insect predators of the genus Naucoris, and very likely their vegetarian preys.
      Coelomic plasmatocytes could be the first cells of Naucoris cimicoides to be
      involved in the infection process, acting as shuttle cells that deliver M.
      ulcerans to the salivary glands as suggested by both in vitro and in vivo
      approaches. Furthermore, a key element for the early and long-term establishment
      of M. ulcerans in Naucoridae is demonstrated by the fact that only mycolactone
      toxin-producing M. ulcerans isolates are able to invade the salivary glands, a
      site where they proliferate. Later, the raptorial legs of Naucoris are covered by
      M. ulcerans-containing material that displays features of biofilms.

PMID- 15953027
TI  - Extracellular group A Streptococcus induces keratinocyte apoptosis by
      dysregulating calcium signalling.
AB  - Group A Streptococcus (GAS) colonizes the oropharynx and damaged skin. To cause
      local infection or severe invasive syndromes the bacteria must gain access into
      deeper tissues. Host cell death may facilitate this process. GAS internalization
      has been identified to induce apoptosis. We now report an alternate mechanism of
      GAS-mediated apoptosis of primary human keratinocytes, initiated by extracellular
      GAS and involving dysregulation of intracellular calcium to produce endoplasmic
      reticulum stress. Two bacterial virulence factors are required for effective
      induction of apoptosis by extracellular GAS: (i) hyaluronic acid capsule that
      inhibits bacterial internalization and (ii) secreted cytolysin, streptolysin O
      (SLO), that forms transmembrane pores that permit extracellular calcium influx
      into the cytosol. Induction of keratinocyte apoptosis by wild-type GAS was
      accompanied by cell detachment and loss of epithelial integrity, a phenomenon not
      observed with GAS deficient in capsule or SLO. We propose that cell signalling
      initiated by extracellular GAS compromises the epithelial barrier by inducing
      premature keratinocyte differentiation and apoptosis, thereby facilitating GAS
      invasion of deeper tissues.

PMID- 15953028
TI  - Modulation of biogenesis of the Francisella tularensis subsp. novicida-containing
      phagosome in quiescent human macrophages and its maturation into a phagolysosome
      upon activation by IFN-gamma.
AB  - Francisella tularensis is a highly virulent facultative intracellular pathogen
      that has been categorized as a class A bioterrorism agent, and is classified into
      four subsp, tularensis, holarctica, mediasiatica and novicida. Although the
      ability of F. tularensis subsp. novicida to cause tularemia in mice is similar to
      the virulent subsp. tularensis and holarctica, it is attenuated in humans. It is
      not known whether attenuation of F. tularensis subsp. novicida in humans is
      resulting from a different route of trafficking within human macrophages,
      compared with the tularensis or holarctica subsp. Here we show that in quiescent
      human monocytes-derived macrophages (hMDMs), the F. tularensis subsp. novicida
      containing phagosome (FCP) matures into a late endosome-like stage that acquires
      the late endosomal marker LAMP-2 but does not fuse to lysosomes. This modulation
      of phagosome biogenesis by F. tularensis is followed by disruption of the
      phagosome at 4-12 h and subsequent bacterial escape into cytoplasm where the
      organism replicates. In IFN-gamma-activated hMDMs, intracellular replication of
      F. tularensis is completely inhibited, and is associated with failure of the
      organism to escape from the phagosome into the cytoplasm for up to 24 h after
      infection. In IFN-gamma-activated hMDMs, the FCPs acquire the lysosomal enzymes
      Cathepsin D, which is excluded in quiescent hMDMs. When the lysosomes of IFN
      gamma-activated hMDMs are preload with Texas Red Ovalbumin or BSA-gold, the FCPs
      acquire both lysosomal tracers. In contrast, both lysosomal tracers are excluded
      from the FCPs within quiescent hMDMs. We conclude that although F. tularensis
      subsp. novicida is attenuated in humans, it modulates biogenesis of its phagosome
      into a late endosome-like compartment followed by bacterial escape into the
      cytoplasm within quiescent hMDMs, similar to the virulent subsp. tularensis. In
      IFN-gamma-activated hMDMs, the organism fails to escape into the cytoplasm and
      its phagosome fuses to lysosomes, similar to inert particles.

PMID- 15953029
TI  - The Francisella tularensis pathogenicity island protein IglC and its regulator
      MglA are essential for modulating phagosome biogenesis and subsequent bacterial
      escape into the cytoplasm.
AB  - The Francisella tularensis subsp. novicida-containing phagosome (FCP) matures
      into a late endosome-like stage that acquires the late endosomal marker LAMP-2
      but does not fuse to lysosomes, for the first few hours after bacterial entry.
      This modulation in phagosome biogenesis is followed by disruption of the
      phagosome and bacterial escape into the cytoplasm where they replicate. Here we
      examined the role of the Francisella pathogenicity island (FPI) protein IglC and
      its regulator MglA in the intracellular fate of F. tularensis subsp. novicida
      within human macrophages. We show that F. tularensis mglA and iglC mutant strains
      are defective for survival and replication within U937 macrophages and human
      monocyte-derived macrophages (hMDMs). The defect in intracellular replication of
      both mutants is associated with a defect in disruption of the phagosome and
      failure to escape into the cytoplasm. Approximately, 80-90% of the mglA and iglC
      mutants containing phagosomes acquire the late endosomal/lysosomal marker LAMP-2
      similar to the wild-type (WT) strain. Phagosomes harbouring the mglA or iglC
      mutants acquire the lysosomal enzyme Cathepsin D, which is excluded from the
      phagosomes harbouring the WT strain. In hMDMs in which the lysosomes are
      preloaded with BSA-gold or Texas Red Ovalbumin, phagosomes harbouring the mglA or
      the iglC mutants acquire both lysosomal tracers. We conclude that the FPI protein
      IglC and its regulator MglA are essential for modulating phagosome biogenesis and
      subsequent bacterial escape into the cytoplasm. Therefore, acquisition of the
      FPI, within which iglC is contained, is essential for the pathogenic evolution of
      F. tularensis to evade lysosomal fusion within human macrophages and cause
      tularemia. This is the first example of specific virulence factors of F.
      tularensis that are essential for evasion of fusion of the FCP to lysosomes.

PMID- 15953030
TI  - Autophagy induction favours the generation and maturation of the Coxiella
      replicative vacuoles.
AB  - Pathogens evolved mechanisms to invade host cells and to multiply in the cytosol
      or in compositionally and functionally customized membrane-bound compartments.
      Coxiella burnetii, the agent of Q fever in man is a Gram-negative gamma
      proteobacterium which multiplies in large, acidified, hydrolase-rich and
      fusogenic vacuoles with phagolysosomal-like characteristics. We reported
      previously that C. burnetii phase II replicative compartments are labelled by
      LC3, a protein specifically localized to autophagic vesicles. We show here that
      autophagy in Chinese hamster ovary cells, induced by amino acid deprivation prior
      to infection with Coxiella increased the number of infected cells, the size of
      the vacuoles, and their bacterial load. Furthermore, overexpression of GFP-LC3 or
      of GFP-Rab24 - a protein also localized to autophagic vacuoles - likewise
      accelerated the development of Coxiella-vacuoles at early times after infection.
      However, overexpression of mutants of those proteins that cannot be targeted to
      autophagosomes dramatically decreased the number and size of the vacuoles in the
      first hours of infection, although by 48 h the infection was similar to that of
      non-transfected controls. Overall, the results suggest that transit through the
      autophagic pathway increases the infection with Coxiella by providing a niche
      more favourable to their initial survival and multiplication.

PMID- 15953031
TI  - Dynamic properties of Legionella-containing phagosomes in Dictyostelium amoebae.
AB  - The natural hosts of the bacterial pathogen Legionella pneumophila are amoebae
      and protozoa. In these hosts, as in human macrophages, the pathogen enters the
      cell through phagocytosis, then rapidly modifies the phagosome to create a
      compartment that supports its replication. We have examined L. pneumophila entry
      and behaviour during early stages of the infection of Dictyostelium discoideum
      amoebae. Bacteria were labelled with a red fluorescent marker, and selected
      proteins and organelles in the host were labelled with GFP, allowing the dynamics
      and interactions of L. pneumophila -containing phagosomes to be tracked in living
      cells. These studies demonstrated that entry of L. pneumophila is an actin
      mediated process, that the actin-binding protein coronin surrounds the nascent
      phagosome but dissociates immediately after internalization, that ER membrane is
      not incorporated into a phagosome during uptake, that the newly internalized
      phagosome is rapidly transported about the cell on microtubules, that association
      of ER markers with the phagosome occurs in two steps that correlate with distinct
      changes in phagosome movement, and that the vacuolar H(+)-ATPase does not
      associate with mature replication vacuoles. These studies have clarified certain
      aspects of the infection process and provided new insights into the dynamic
      interactions between the pathogen and its host.

PMID- 15953032
TI  - Neisseria gonorrhoeae downregulates expression of the human antimicrobial peptide
      LL-37.
AB  - Neisseria gonorrhoeae is a human pathogen causing the sexually transmitted
      disease gonorrhoeae. The bacteria preferentially attach to and invade epithelial
      cells of the genital tract. As these cells previously have been shown to express
      the human cathelicidin LL-37, we wanted to investigate the role of LL-37 during
      N. gonorrhoeae infection. The cervical epithelial cell line ME180 was utilized
      and the expression of LL-37 was confirmed on both peptide and transcriptional
      levels. Moreover, LL-37 exhibited potent in vitro activity against N.
      gonorrhoeae. Interestingly, the transcript and peptide levels of LL-37 were
      downregulated during infection, according to quantitative real-time polymerase
      chain reaction (PCR) and immunocyto-chemistry. The downregulation was most
      prominent with pathogenic strains of Neisseria, while non-pathogenic strains such
      as Neisseria lactamica and Escherichia coli only exhibited moderate effects. Heat
      killed N. gonorrhoeae had no impact on the downregulation, emphasizing the
      importance of live bacteria. The results in this study suggest that pathogenic
      Neisseria may gain a survival advantage in the female genital tract by
      downregulating LL-37 expression.

PMID- 15953034
TI  - The increase in mucin exocytosis and the upregulation of MUC genes encoding for
      membrane-bound mucins induced by the thiol-activated exotoxin listeriolysin O is
      a host cell defence response that inhibits the cell-entry of Listeria
      monocytogenes.
AB  - In vivo Listeria monocytogenes infection results in the massive release of mucus
      by goblet cells into the lumen of the intestine. We have previously reported that
      apical infection by L. monocytogenes is followed by listeriolysin O (LLO)
      dependent stimulation of mucus exocytosis, and the upregulation of the MUC genes.
      Here, we report that L. monocytogenes EGD wild-type bacteria enter cultured human
      polarized, mucin-secreting, HT29-MTX cells apically by an InlA-dependent
      mechanism. The LLO-induced increase in mucin secretion together with an increase
      in transcription of the MCU4 and MUC12 genes encoding for membrane-bound mucins,
      results in the inhibition of the cell-entry of L. monocytogenes into mucin
      secreting, HT29-MTX cells. Moreover, we report that sialic acid residues in
      mucins are crucial for the inhibition of L. monocytogenes internalization. Based
      on these findings, we suggest that the LLO-induced mucin exocytosis and
      upregulation of the MUC genes encoding for membrane-bound mucins constitute a
      host cell defence response that inhibits the cell-entry of L. monocytogenes.

PMID- 15953033
TI  - Unusual trafficking pattern of Bartonella henselae -containing vacuoles in
      macrophages and endothelial cells.
AB  - Bartonella henselae, the agent of cat-scratch disease and vasculoproliferative
      disorders in humans, is a fastidious facultative intracellular pathogen, whose
      interaction with macrophages and endothelial cells (ECs) is crucial in the
      pathogenesis of these diseases. However, little is known about the subcellular
      compartment in which B. henselae resides. Two hours after infection of murine
      macrophages and human ECs, the majority of B. henselae-containing vacuoles (BCVs)
      lack typical endocytic marker proteins, fail to acidify, and do not fuse with
      lysosomes, suggesting that B. henselae resides in a non-endocytic compartment. In
      contrast to human umbilical vein endothelial cells, bacterial death and lysosomal
      fusion with BCVs is apparent in J774A.1 macrophages at 24 h. This phenomenon of
      delayed lysosomal fusion requires bacterial viability, and is confined to the BCV
      itself. Using magnetic selection, we enriched for transposon-mutagenized B.
      henselae trapped in lysosomes of macrophages 2 h after infection. Genes affected
      appear to be relevant to the intracellular lifestyle in macrophages and ECs and
      include some previously implicated in Bartonella pathogenicity. We conclude that
      B. henselae has a specific capacity to actively avoid the host endocytic pathway
      after entry of macrophages and ECs, from within a specialized non-endocytic
      membrane-bound vacuole.

PMID- 15953037
TI  - Abstracts of the 2nd World Union of Wound Healing Societies, Paris, France, July
      8-13, 2004.

PMID- 15953038
TI  - A matter of ethics.

PMID- 15953039
TI  - Efficacy of modern dressings in the treatment of leg ulcers: a systematic review.
AB  - Healing of leg ulcers constitutes a major clinical problem. Local methods for
      accelerating the healing process include modern wound dressings, but it is
      unclear what impact these dressings have on ulcer healing. This study examines
      the collective evidence on the effectiveness of modern dressings in the treatment
      of leg ulcers. To this end, a meta-analysis was conducted covering randomized
      clinical trials identified following a systematic review of the literature in
      different databases. Estimates of effect were calculated according to the fixed
      effects model. Thirty-one studies met the inclusion criteria (26 on ulcers of
      venous etiology, 5 on ulcers of mixed or poorly differentiated etiology). We
      found no study that exclusively addressed arterial ulcers. Although studies
      displayed considerable methodological limitations, analysis showed no significant
      differences in terms of the proportion of healed ulcers or reduction in wound
      size for both modern and conventional dressings. Similarly, no significant
      differences were observed between the different modern dressings compared in the
      studies. Thus, the current medical literature is poor in supporting the use of
      modern dressings to improve the healing rate of leg ulcers. There is insufficient
      evidence to determine whether the choice of any specific dressing type affects
      the healing course of these ulcers. Well-conducted trials are warranted to
      reliably address this question.

PMID- 15953040
TI  - Diabetic neuropathic foot ulcers and amputation.
AB  - A neuropathic foot ulcer is a severe complication of diabetes that can result in
      a more severe complication, a lower extremity amputation. We conducted a cohort
      study of 24,616 individuals with a diabetic neuropathic foot ulcer treated within
      a multicenter wound care network. A total of 1653 (6.7%) individuals had an
      amputation and 46.3% of these amputations were of a toe or ray (minor
      amputation). In the more than 10-year follow-up period that we studied, the
      percentage of those who had an amputation varied between 5.6% and 8.4%. Of those
      who had an amputation, the percentage that had a minor amputation increased over
      time from 4.0% in the earliest years to more than 60% in the later years of
      observation. The single most important determinant of amputation was the
      observation of fascia, tendon, and bone at the initial assessment. In conclusion,
      about 7% of those with a diabetic neuropathic foot ulcer will have an amputation
      and in the past 10 years there has been a remarkable increase in the number of
      minor as compared to major amputations.

PMID- 15953041
TI  - Treatment of deep sternal wound infections post-open heart surgery by application
      of activated macrophage suspension.
AB  - Postoperative sternal wound infection remains a significant complication and
      generally causes considerable morbidity and mortality. Macrophages play a major
      role in the process of wound healing. In order to evaluate the efficacy of local
      injection of activated macrophage suspensions into open infected sternal wound
      space, a retrospective case-control study was conducted. Sixty-six patients with
      deep sternal wound infection treated by activated macrophages (group 1) and 64
      patients with deep sternal wound infection treated by sternal reconstruction
      surgery with various regional flaps (group 2), were matched for gender, age, and
      risk index. In up to 54 months of follow-up of group 1, 60 patients (91%)
      achieved complete wound closure. Two (3%) late deaths occurred unrelated to the
      procedure. Mortality rate in group 2 was 29.7% (19/64). Duration of
      hospitalization was 22.6 days in group 1 vs. 56.2 days in group 2. Patients with
      deep sternal wound infection following open heart surgery that were treated by
      activated macrophages had significantly less mortality as well as significant
      reduction of hospitalization in comparison to the surgically treated group. These
      results illustrate the advantages of using a biologically based activated
      macrophage treatment.

PMID- 15953042
TI  - Initial report of the use of an injectable porcine collagen-derived matrix to
      stimulate healing of diabetic foot wounds in humans.
AB  - A novel injectable scaffolding matrix (E-Matrix) has been developed to accelerate
      wound healing in diabetic foot ulcers. This porcine collagen-derived matrix is
      designed to mimic tertiary embryonic connective tissue and to stimulate fetal
      wound repair mechanisms including angiogenesis. In vitro and animal studies have
      indicated a beneficial effect on tissue growth and an acceptable safety profile.
      In this report, we describe the initial use of this product in a pilot study of
      six humans with chronic nonhealing diabetic foot ulcers. A dramatic initial
      response to injection was seen, with an average wound size reduction of 72% 2
      weeks after injection. Randomized trials are underway to define the potential
      benefit of this new treatment modality for diabetic foot ulcers.

PMID- 15953043
TI  - Low recruitment of immune cells with increased expression of endothelial adhesion
      molecules in margins of the chronic diabetic foot ulcers.
AB  - Diabetic foot skin close to an ulcer shows only a few infiltrating cells compared
      to nondiabetic inflamed tissues. Diabetes is characterized by thickened basement
      membrane of the blood arterioles and capillaries. This may affect the
      transcapillary transport of immune humoral factors and cells to the extravascular
      space. We analyzed by immunohistochemistry the phenotype and expression pattern
      of adhesion molecules on leukocyte, dermal fibroblast, and endothelial cells in
      diabetic foot ulcers. Although there was accumulation of granulocytes on the
      surface and superficial layers of the granulation tissue, rare perivascular
      granulocyte infiltrates in the dermis were seen. Moreover, lack of macrophage and
      CD3+ T cell infiltrates was observed. In contrast, there was increased intensity
      of CD1a staining of Langerhans cells in the epidermis and papillary dermis (p <
      0.05). Fibroblasts revealed increased presence in the ulcer margins compared with
      normal skin (p < 0.05). Skin endothelial cells expressed stronger von Willebrand
      factor and E-selectin compared with normal skin (p < 0.05). Our study provides
      evidence that increased expression of endothelial cell adhesion molecules
      responsible for immunocyte extravasation is not associated with increased
      inflammatory cell infiltration of the ulcerated diabetic foot tissue. We suggest
      that the healing process of diabetic foot ulcers may be hampered by mechanisms
      decreasing accumulation of leukocytes. This implies that pharmacological or
      biological stimulation of leukocyte extravasation into the ulcer tissue should be
      tried.

PMID- 15953044
TI  - Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase
      28) expression in hypertrophic scars.
AB  - Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of
      this family of proteases expressed by keratinocytes in response to an injury. MMP
      28's physiological role and specific substrates are unknown, but its expression
      pattern suggests that it may serve a role in both tissue homeostasis and wound
      healing. The aim of this preliminary study was to observe the presence of MMP-28
      protein in normotrophic and hypertrophic scars and to evaluate the effect of in
      vitro mechanical compression on its expression. Biopsies from normotrophic and
      hypertrophic scars resulting from burns were divided into two samples, one to be
      used as control (uncompressed) and the other to be compressed in an oxygenated
      organ chamber for 24 hours in the presence of a serum-free medium, using an
      electromechanical load transducer (stable pressure = 35 mmHg). Analysis of MMP-28
      protein secretion, assessed by Western blot and beta-casein zymography in scar
      conditioned media, revealed that normotrophic scar did not release MMP-28 in any
      condition while hypertrophic scar released active MMP-28 both in control
      conditions and after compression. MMP-28 immunohistochemistry revealed a light
      protein presence in normotrophic scar keratinocytes and a strong MMP-28
      positivity in hypertrophic scar keratinocytes in control conditions, while
      compression increased MMP-28 staining in normotrophic scar and induced a
      significant reduction of the protein presence in hypertrophic scar keratinocytes.
      As it has been suggested that MMP-28 may restructure the skin basal membrane
      (Saarialho-Kere et al., 2002), our data indicate that mechanical compression
      directly acts to modulate the remodeling phase of wound healing, altering release
      and activity of MMP-28 in hypertrophic scars.

PMID- 15953045
TI  - Comparison of the effectiveness of gene therapy with transforming growth factor
      beta or extracorporal shock wave therapy to reduce ischemic necrosis in an
      epigastric skin flap model in rats.
AB  - The induction of neoangiogenesis by exogenous growth factors in failing skin
      flaps has recently yielded promising results. Gene transfer with virus vectors
      has been introduced as a highly capable route of administration for growth
      factors, such as vascular endothelial growth factor or fibroblast growth factor.
      Extracorporal shock waves (ESW) deliver energy by means of high amplitudes of
      sound to the target tissue and have been shown to induce angiogenesis. We
      compared the effectiveness of gene therapy with adenovirus-mediated transforming
      growth factor-beta (TGF-beta) and ESW therapy to treat ischemically challenged
      epigastric skin flaps in a rat model. Thirty male Sprague-Dawley rats were
      divided into three groups of 10 each with an 8 x 8 cm epigastric skin flap. Rats
      received either subdermal injections of adenovirus (Ad) encoding TGF-beta (10(8)
      pfu) or ESW treatment with 750 impulses at 0.15 mJ/mm2. The third group received
      no treatment and served as a control group. Flap viability was evaluated after 7
      days and digital images of the epigastric flaps were taken and areas of necrotic
      zones relative to total flap surface area calculated. Histologic evaluation and
      increased angiogenesis were confirmed by CD31 immunohistochemistry. Overall,
      there was a significant increase in mean percent surviving area in the Ad-TGF
      beta group and the ESW group compared to the control group (ESW group: 97.7 +/-
      1.8% vs. Ad-TGF-beta: 90.3 +/- 4.0% and control group: 82.6 +/- 4.3%; p < 0.05).
      Furthermore, in the ESW group mean percent surviving areas were significantly
      larger than in the Ad-TGF-beta group (ESW group: 97.7 +/- 1.8% vs. Ad-TGF-beta:
      90.3 +/- 4.0%; p < 0.05). Flap vascularization was increased by Ad-TGF-beta and
      ESW with numerous vessels, however, there was no significant difference between
      the two treatment groups. We conclude that treatment with ESW enhances epigastric
      skin flap survival significantly more than Ad-TGF-beta treatment and thus
      represents a modality that is feasible, cost-effective, and less invasive
      compared to gene therapy with growth factors to improve blood supply to ischemic
      tissue.

PMID- 15953046
TI  - Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene
      transfer with growth factors on collagen expression in acute wounds.
AB  - Growth factors have been shown to modulate the complex cascade of wound healing,
      however, interaction between different growth factors during dermal and epidermal
      regeneration is still not entirely defined. We have recently shown that exogenous
      liposomal gene transfer of cDNA results in physiologic expression and response in
      an acute wound. In the present study we determined the interaction between
      insulin-like growth factor-I (IGF-I), a mesenchymal growth factor, administered
      as liposomal cDNA, with other dermal and epidermal growth factors on collagen
      synthesis in an acute wound. Sprague-Dawley rats were given a scald burn to
      inflict an acute wound and divided into two groups to receive weekly subcutaneous
      injections of liposomes plus a beta-galactosidase containing plasmid (Lac Z [0.2
      microg, vehicle]), or liposomes plus the IGF-I cDNA containing plasmid (2.2
      microg) and Lac Z (0.2 microg). Immunological assays, histological and
      immunohistochemical techniques were used to determine growth factor concentration
      and different types of collagen (I, III, and IV) after IGF-I cDNA gene transfer.
      IGF-I cDNA transfer accelerated reepithelization and was associated with
      increased levels of IGF-I, fibroblast growth factor, keratinocyte growth factor,
      vascular endothelial cell growth factor, and platelet-derived growth factor
      protein expression. IGF-I cDNA had no effect on transforming growth factor-beta.
      IGF-I cDNA significantly increased type IV collagen while it had no effect on
      types I and III collagen. Exogenously administered IGF-I cDNA increased protein
      concentrations of keratinocyte growth factor, fibroblast growth factor, platelet
      derived growth factor, and type IV collagen. We conclude that liposomal IGF-I
      gene transfer can accelerate wound healing without causing an increase in types I
      and III collagen expression.

PMID- 15953047
TI  - Experimental ischemic wounds: correlation of cell proliferation and insulin-like
      growth factor I expression and its modification by different local IGF-I release
      systems.
AB  - We investigated cell proliferation and local insulin-like growth factor-I (IGF-I)
      expression in ischemic wounds after topical application of IGF-I through
      different delivery systems. IGF-I dressings were fabricated from an IGF-I
      containing polyvinyl alcohol film placed on a standard hydrogel dressing. In
      vitro, the release of IGF-I from this dressing was assessed by enzyme-linked
      immunosorbent assay. For animal experiments, a standardized ischemic skin flap
      containing a full-thickness wound was created on the back of male Sprague-Dawley
      rats. An identical wound outside the flap served as control. We initially
      investigated intracutaneous pO2 (p(ti)O2), cell proliferation, and local IGF-I
      expression. In a second setting, wounds were treated either with IGF-I dissolved
      in methylcellulose gel or with an IGF-I dressing, and ulcer size and cell
      proliferation were assessed. In vitro, approximately 60% of IGF-I was released
      from the IGF-I dressing, compared to a 97% release from methylcellulose gel. In
      vivo, ischemic wounds showed less cell proliferation and decreased IGF-I
      expression than nonischemic wounds. A lower local p(ti)O2 correlated with larger
      wound size, less cell proliferation, and decreased IGF-I expression. Ulcer size
      was reduced after treatment with either IGF-I dressing or methylcellulose gel.
      However, cell proliferation only increased after treatment with IGF-I dressing,
      but not after methylcellulose gel treatment. We conclude that IGF-I expression is
      decreased in ischemic wounds and correlates with low cell proliferation. This can
      be reversed by local IGF-I application, but the efficacy of treatment depends on
      the delivery system.

PMID- 15953048
TI  - Activated protein C prevents inflammation yet stimulates angiogenesis to promote
      cutaneous wound healing.
AB  - Activated protein C (APC) is a serine protease that plays a central role in
      physiological anticoagulation, and has more recently been shown to be a potent
      anti-inflammatory mediator. Using cultured human cells, we show here that APC up
      regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts
      and umbilical vein endothelial cells, vascular endothelial growth factor in
      keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in
      fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the
      granulation/remodeling phases of wound healing by markedly stimulating
      angiogenesis as well as promoting reepithelialization. In a full-thickness rat
      skin-healing model, a single topical application of APC enhanced wound healing
      compared to saline control. APC-treated wounds had markedly more blood vessels on
      day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The
      broad spectrum matrix metallo-proteinase, GM6001, prevented the ability of APC to
      promote wound healing. In summary, our results show that APC promotes cutaneous
      wound healing via a complex mechanism involving stimulation of angiogenesis and
      inhibition of inflammation. These unique properties of APC make it an attractive
      therapeutic agent to promote the healing of chronic wounds.

PMID- 15953049
TI  - Effect of diabetes mellitus and hyperglycemia on the proliferation of human
      Tenon's capsule fibroblasts: implications for wound healing after glaucoma
      drainage surgery.
AB  - Glaucoma drainage surgery in diabetic patients is associated with a relatively
      poor prognosis due to increased scarring at the site of surgery, secondary to
      increased proliferation of human Tenon's capsule fibroblasts (hTCF). This is in
      marked contrast to diabetic wound healing at other sites, where it is generally
      impaired. The aim of this study was to determine why diabetics show an increased
      ocular scarring response in comparison to that found at other sites. Under
      normoglycemic conditions, hTCF isolated from diabetics showed a mean reduction in
      short-term proliferation (95% CI) of 45 +/- 12% compared with normal controls (p
      < 0.001). Under hyperglycemic conditions, proliferation of diabetic hTCF was
      reduced by 21 +/- 11% (p < 0.01) compared with nondiabetic controls. When exposed
      to transforming growth factor-beta2 (1-10,000 pg/ml) and platelet-derived growth
      factor-BB (0.5-500 ng/ml) under both normo- and hyperglycemic conditions, there
      was a dose-related increase in proliferation of both diabetic and nondiabetic
      controls. There was no significant difference in response to cytokine stimulation
      between the two groups at any of the cytokine concentrations used. Western blot
      analysis did not show any apparent difference in the expression of platelet
      derived growth factor receptor alpha, mitogen-activated protein kinase/ERK2, or
      transforming growth factor-beta receptor II to account for the reduced
      proliferation of diabetic hTCF. These results suggest that hTCF behave in a
      manner similar to fibroblasts from other nonocular sites and that the increased
      proliferation and scarring response found in vivo may be secondary to the
      previously noted elevated cytokine concentrations in the aqueous and vitreous of
      diabetics.

PMID- 15953050
TI  - Hyperoxia improves microvascular perfusion in a murine wound model.
AB  - There is a need for a noninvasive method that measures wound angiogenesis.
      Hyperoxia is known to increase the appearance of new blood vessels in wounds, yet
      no study has confirmed increases in wound bed perfusion with periodic hyperbaric
      oxygen (HBO) exposure. This study investigates whether laser Doppler imaging is
      able to detect and quantify the enhancement of wound angiogenesis that is known
      to occur with intermittent HBO treatments. Full-thickness dorsal dermal wounds
      were created on mice randomized to hyperoxic (n = 14) and control (n = 15)
      groups. Hyperbaric oxygen was administered twice daily for 90 minutes each at 2.1
      atmospheres for 7 days. Wound bed perfusion was measured by laser Doppler imaging
      on days 0, 7, and 10 postwounding. Wound blood flow increased significantly over
      baseline on day 7 and 10 in the hyperoxic group, but only on day 10 in the
      control group. Comparison between groups showed a 20% statistically significant
      increase in wound perfusion in HBO-treated animals compared to control on day 10
      (p = 0.05). Laser Doppler imaging was able to detect and quantify the increase in
      wound bed perfusion resulting from intermittent HBO treatments and shows promise
      as a noninvasive measure of angiogenesis and wound healing.

PMID- 15953051
TI  - Effect of NorLeu3-A(1-7) on scar formation over time after full-thickness
      incision injury in the rat.
AB  - Previous studies have shown that the angiotensin peptide NorLeu3-A(1-7)
      accelerates dermal healing and reduces scar formation. In this report, the effect
      of this peptide on scar formation is more fully delineated. The effect of
      surgical day, time after injury, and observer on the clinical appearance of the
      incision were determined. Clinical observations of incision site, including
      inflammation, opening of the injury, and appearance of scar, were conducted by
      two observers blinded to treatment (two observations per time point) twice
      weekly. Opening of the incision occurred in 35-40% of incisions early (days 4 and
      7) after injury. Administration of NorLeu3-A(1-7) at the time of injury reduced
      the incidence of opening at day 7 to approximately 20%. Further, the length of
      the wound opening was significantly reduced in the peptide-treated incisions at
      day 7. Starting on day 14 after injury, scar formation was evaluated. Up to 80
      90% of control animals had observable scars starting on day 14. Thereafter, the
      scar remodeled with fewer incisions having visible scar on day 28. With
      administration of NorLeu3-A(1-7), significantly fewer incisions had observable
      scars starting on day 14 and throughout the study. As few as 20% of the incisions
      had observable scars on day 28. The histological appearance of the healing wound
      was also evaluated at weekly intervals starting on day 7 and continued until day
      42. At day 7, the maximal number of fibroblasts at the wound site was observed.
      Thereafter, the number gradually reduced, reaching a plateau at day 28. The
      administration of peptide had no effect on fibroblast number at the incision
      site. A similar pattern was observed in the thickness of the epidermis with the
      resolution of the hyperplastic phase at day 21. Administration of the peptide
      significantly increased epidermal height at day 7. Blood vessel formation peaked
      on day 21 and 28 in control wounds and was further enhanced by peptide
      administration during the neovascularization phase. After day 28, blood vessel
      number was comparable between control and treated incisions. Collagen deposition
      and remodeling were increased by the administration of NorLeu3-A(1-7) at the time
      of injury.

PMID- 15953052
TI  - Wound healing and degradation of the fibrin sealant Beriplast P following partial
      liver resection in rabbits.
AB  - The objective of this study was to investigate the degradation kinetics of the
      fibrin sealant (FS) Beriplast P in an experimental liver surgery model in
      rabbits. A partial liver resection was performed in 21 rabbits, and the wound
      area covered with Beriplast P to ensure hemostasis. Wound healing of the
      resection sites was evaluated morphologically over 11 weeks. Degradation of the
      FS was evaluated by measuring the thickness of the remaining fibrin layer. Plasma
      samples were analyzed for antibodies against fibrinogen, albumin, thrombin,
      fibrin, and factor XIII. No postoperative hemorrhage was observed, indicating
      successful hemostasis throughout. The FS was degraded with a half-life of about
      25 days postapplication and was completely replaced by granulation tissue within
      9 weeks. The FS degradation and tissue development followed the general stages of
      wound healing: inflammation and resorption, proliferation, organization and
      production of collagen, maturation, and scarring. An immune reaction was elicited
      against the main four human proteins of the FS. The antibody titers peaked on day
      14, with a gradual decrease thereafter. We conclude that the FS accomplished
      hemostasis, facilitated healing in accordance with natural processes, and was
      completely degraded over time. In humans, the reduced immunogenicity of the FS
      would potentially increase its degradation half-life.

PMID- 15953053
TI  - Effect of oxidized regenerated cellulose/collagen matrix on dermal and epidermal
      healing and growth factors in an acute wound.
AB  - Rapid healing of acute wounds, e.g., in burned patients, can be essential for
      survival. Oxidized regenerated cellulose/collagen (ORC/collagen) has been shown
      to improve wound healing of chronic wounds. The aim of the present study was to
      determine the effect of ORC/collagen on dermal and epidermal healing as well as
      growth factor concentration in acute wounds. Rats received a full-thickness
      excision wound and were treated with either ORC/collagen plus a hydrocolloid
      dressing or a hydrocolloid dressing alone. Planimetry, immunological assays,
      histological and immunohistochemical techniques were used to determine dermal and
      epidermal regeneration, protein concentration, and growth factor concentration.
      In addition, dermal vascularization and structure were determined. Wounds treated
      with ORC/collagen showed a significantly faster reepithelization than those
      treated with hydrocolloid alone, p < 0.05. This accelerated wound healing rate
      may be explained by significantly higher levels of platelet-derived growth
      factor, keratinocyte growth factor, insulin-like growth factor-I, and insulin
      like growth factor binding protein-3 in the ORC/collagen group leading to
      antiapoptotic effects of skin cells, p < 0.05. There were no significant
      differences in collagen morphology or deposition, neo-angiogenesis, or vascular
      endothelial growth factor concentration between both treatment groups. We
      conclude that ORC/collagen matrix accelerates epidermal regeneration and locally
      increases growth factor concentrations. Increased reepithelization was associated
      with decreased skin cell apoptosis. Based on our data we hypothesize that the
      ORC/collagen matrix may also have beneficial effects on acute wounds in a
      clinical setting.

PMID- 15953054
TI  - Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic
      cytokines via nutrient vessel injection in a nude rat model.
AB  - In vivo studies using bone marrow-derived mesenchymal stem cells are still
      uncommon. Applications for bone defect replacement in undesirable clinical
      circumstances such as large defects, bacterial or other pathogen-contaminated
      fields, and irradiated surgical wound bed necessitate vascularized bone
      regeneration. Use of a fascial flap including regenerated bone would be a very
      powerful tool for treatment. It would be especially beneficial in cases where
      normal bone regeneration is not expected due to a lack of sufficient blood
      supply, extensive surgical scarring, or bacterial contamination. In this study,
      we used nude rats in which the superficial epigastric flap of the experimental
      group was used to wrap around a mixture of human mesenchymal stem cells, bone
      morphogenetic protein-2, and basic fibroblast growth factor cytokines in a
      gelatin carrier. These rats showed significantly higher bone mineral density at 4
      weeks compared to the other experimental groups containing phosphate buffered
      saline, human mesenchymal stem cells alone, or the two cytokines alone (p <
      0.01). There were no remarkable histologic differences up to 7 days. At 2 weeks,
      more progressive vascularity and perivascular tissue deposits were seen in the
      experimental group. Basophilic mineral structure surrounded the fibroblast-like
      mesenchymal stem cells at 4 weeks, presumably osteoblastic or osteoclastic cell
      lining. Bone marker immunohistochemistry against alkaline phosphatase and
      osteocalcin revealed diffuse and distinct immunoreactivity in osteoblastic cells
      in the experimental group at 4 weeks. Further transcriptional expression of
      polyomavirus enhancer binding protein 2alphaA suggested that the human
      transplanted cells proceeded to osteogenic lineage in 4 weeks. These results may
      be useful as a new approach for bone regeneration.

PMID- 15953055
TI  - Cell origin in experimental repair of cricoid cartilage defects treated with
      recombinant human bone morphogenetic protein-2.
AB  - We determined the origin of new cartilage and new bone induced by recombinant
      human bone morphogenetic protein-2 (rhBMP-2) at the site of cricoid cartilage
      defects in rabbits randomly divided into eight groups. The cricoid cartilage was
      split vertically along the anterior midline and a strip was excised from the
      anterior part of the cricoid cartilage in all rabbits. The perichondrium from the
      anterior part of the cricoid cartilage was trimmed off in four groups; two groups
      treated with rhBMP-2 and two control groups. In four other groups, the anterior
      perichondrium was detached and used as a flap with two groups treated with rhBMP
      2 and two groups serving as controls. The rabbits were killed 1 week or 4 weeks
      after surgery. The larynges were removed, fixed and sectioned, and the sections
      were stained for light microscopy using various cytochemical and immunological
      techniques. New cartilage was only present close to the host perichondrium
      adherent to cricoid cartilage in rabbits treated with rhBMP-2. New bone was
      present 4 weeks after surgery, although calcified matrix and alkaline phosphatase
      activity could be detected at the site of cricoid defects as early as 1 week
      after surgery. The cell proliferation marker Ki-67 was strongly expressed in
      granulation tissue and bone marrow, and it was moderately expressed in muscles
      adjacent to the cricoid cartilage in rhBMP-2-treated specimens. BMP receptors
      were strongly expressed in cartilage and moderately expressed in adjacent
      muscles. We conclude that new cartilage originates from the mesenchymal
      progenitor cells of host perichondrium adherent to cricoid cartilage in rabbits
      treated with rhBMP-2. New bone may originate from local muscle.

PMID- 15953056
TI  - Maggot therapy and the "yuk" factor: an issue for the patient?

PMID- 15953057
TI  - Co-transplantation of autologous adult stem cells together with differentiated
      derivatives of human embryonic stem cells. A novel strategy to enhance the
      efficacy of autologous cell-transplantation therapy?

PMID- 15953058
TI  - The role of complement testing in dermatology.
AB  - An up-to-date knowledge of the molecular events involved in the activation and
      control of the complement cascade is essential to understand the pathogenesis of
      a number of conditions presenting to dermatologists. This knowledge underpins the
      pathogenesis of these conditions but allows the clinician to request the most
      useful tests in terms of diagnosis and monitoring. In this review we aim to
      discuss complement biology, the diseases in which complement testing is of
      particular relevance, the types of laboratory tests available, their utility and
      interpretation. Additionally it is of critical importance for clinicians not only
      to choose the most appropriate tests but also to choose to send these to an
      appropriately accredited laboratory.

PMID- 15953060
TI  - Narrow-band UVB for the treatment of generalized vitiligo in children.
AB  - Vitiligo usually begins in childhood with approximately half of the patients
      manifesting onset of disease prior to the age of 20 years. Treatment options in
      this age group are few and have disappointing response rates. This study was
      designed to evaluate the role of narrow-band UVB in the treatment of generalized
      vitiligo in children. Twenty-six children (aged 5-14 years) with generalized
      vitiligo (minimal extent of depigmentation of 5% of the skin) were treated three
      times per week with narrow-band UVB therapy for a maximum period of 1 year. Of 26
      patients, 6 were lost to follow up and 20 (7 males, 13 females) completed the
      study. At the end of 1 year of therapy, 15 (75%) patients developed marked to
      complete repigmentation. Moderate and mild repigmentation was noted in four (20%)
      and one (5%) patients, respectively. An average number of 34 (+/- 2) treatment
      visits was required to achieve 50% repigmentation. Adverse events were mild and
      transient. Narrow-band UVB is an effective and well-tolerated treatment option
      for childhood vitiligo.

PMID- 15953059
TI  - Clinical profiles of vitiligo in China: an analysis of 3742 patients.
AB  - Very few articles have aimed to illuminate the clinical profiles of vitiligo in
      China. We conducted this retrospective survey involving 4118 outpatients with
      vitiligo in order to identify the differences among various clinical types of
      vitiligo and their associated disorders. Completed questionnaires (3742) were
      validated and analysed. Of this large cohort, 1565 (41.8%) individuals presented
      vitiligo vulgaris, followed by focal, segmental, acrofacial, and universal, in
      that order. The mean age of vitiligo onset was 18.88 years. More than 60% of the
      patients were affected before 20 years of age. Patients with segmental vitiligo
      were affected earlier than those with other types of vitiligo (15.55 years; (P <
      0.001). More than 74% of the patients presented with focal vitiligo at onset.
      After 3-5 years, 99% of active vitiligo was worse and shifted from one clinical
      type to another. However, there was no transformation between acrofacial vitiligo
      and segmental vitiligo. Compared with the general population, the patients with
      vitiligo were more likely to be affected by rheumatoid arthritis (P < 0.01),
      ichthyosis (P < 0.01), chronic urticaria (P < 0.01), or alopecia areata (P <
      0.01).

PMID- 15953061
TI  - A comparison of narrowband (TL-01) UVB-induced erythemal response at different
      body sites.
AB  - In most dermatology centres where phototesting is performed, the starting dose is
      calculated as a proportion of the minimal erythema dose (MED). Previous studies
      have found significant differences in MED readings between forearm and back skin
      with both broadband and narrowband (NB) UVB. Our objective was to compare MEDs
      obtained from three body sites, the forearm, back and abdomen, to see if there
      was a significant difference in individuals. We recruited 20 healthy volunteers
      who were exposed to our standard dose series for phototesting with NB-UVB to
      three body sites: forearm, back and abdomen. MEDs were assessed 24 h post
      exposure. The median MED for the abdomen was 0.79 J/cm2, the back 0.95 J/cm2 and
      the arm 1.11 J/cm2. Friedman's analysis of variance by ranks showed that these
      differences were significant (P = 0.003). There was no correlation between skin
      type and MED for any of the three anatomical sites. Our results support
      phototesting for all patients prior to treatment with NB-UVB. Furthermore, we
      have shown that the abdomen is the anatomical site of choice for phototesting, as
      this will result in a reduced risk of burning episodes.

PMID- 15953062
TI  - Sun protection initiatives in Cornwall.
AB  - Recent evidence indicates that there are significant numbers of cases of
      malignant melanoma in the UK. In order to assess the current position with regard
      to sun awareness in Cornwall, a questionnaire survey of all state primary school
      heads (n = 123) and a survey of a random sample of GP practices (n = 9) was
      carried out. The data obtained were supported by visits to libraries and Tourist
      Information Centres at urban and rural centres--this enabled the identification
      of sun awareness literature. Key health professionals who worked within the field
      of health promotion were also contacted. The findings showed that in Cornwall
      public campaigns organized around the issue of sun protection took place only
      sporadically, although GP surgeries usually organize a display at the appropriate
      time of the year. None of the public places (e.g. Tourist Information Centres,
      libraries) surveyed had sun protection messages on display. It is concluded that
      insufficient sun awareness initiatives were being undertaken in Cornwall.
      Although most primary schools included sun awareness education in their
      curriculum in a form based on the Sun Awareness Guidelines produced by the
      Department of Health in 1995, few schools considered further measures to protect
      pupils on hot and sunny days. In particular the provision of shade, the
      scheduling of outdoor activities and the use of sunscreen and protective clothing
      were not standard.

PMID- 15953063
TI  - Vitiligo presentation in adults.
AB  - The characteristics of vitiligo in 41 adults presenting to a university
      dermatology clinic in Sheffield, UK were studied in a case review. Of 41
      patients, 29 women and 12 men, there were 37 European Caucasians, three Asian
      Caucasians and one black African. Symmetrical and acrofacial types of vitiligo
      predominated but there were no segmental cases. Age of onset was before 20 years
      in 17, with a mean of 28 years; the oldest onset was 74 years. The average
      duration of the disease was 16 years. Autoimmune thyroid disease was present in
      14 cases (34%). Only seven (18%) gave a family history of vitiligo. A
      precipitating factor was identified in nine (22%), including pregnancy, sunburn
      and skin trauma. Topical steroid treatment was given in 33 and narrow-band
      ultraviolet B was prescribed in nine. This series is unusual in having no cases
      of segmental vitiligo, perhaps because no children are included, and in having a
      high prevalence of thyroid disease.

PMID- 15953064
TI  - Selenium deficiency: report of a case.
AB  - We report an 18-month-old Japanese boy with selenium deficiency. He had dry skin
      with irregularly shaped, erythematous changes on the cheeks, groin, hip, and
      extremities, erosions on the external urethral and anal orifices, and sparse,
      short, thin, light-coloured hair. He had received parenteral nutrition for 5
      months because of juvenile polyposis. At presentation, his serum selenium level
      was less than 2.0 microg/dL (normal range, 10.6-17.4 microg/dL). His skin lesions
      responded well to supplementary treatment with sodium selenite. His skin symptoms
      were similar to those attributable to a deficiency of zinc which, like selenium,
      is an essential trace element. According to the literature, selenium deficiency
      is responsible for cardiomyopathy, which was diagnosed in our patient. The
      clinical similarity to zinc deficiency and the literature yielded important clues
      for a diagnosis of selenium deficiency in this patient.

PMID- 15953065
TI  - Low prevalence of twisted hair in anorexia nervosa.
AB  - In a series of 30 patients affected by severe anorexia nervosa (AN) we examined
      hair samples to detect the prevalence of acquired pili torti (APT). True APT were
      not detected but in two cases (6.6%) twisted hair was observed. The first case
      was a 24-year-old woman with secondary amenorrhoea for 9 years, whose body mass
      index (BMI) was 12.2 kg/m2. She also had severe skin xerosis and hypertrichosis.
      The second case was a 24-year-old woman with secondary amenorrhoea for 1 year,
      whose BMI was 11.3 kg/m2. She also had severe skin and lip xerosis, severe
      effluvium, cystic acne, acrocyanosis, perimylolysis (severe erosion of the
      dentition) and scars due to cigarette burns on her forearms. Reviewing the
      literature we noticed that the largest series of pili torti--congenital and
      acquired--were published by authors from countries such as Israel and Egypt. We
      therefore hypothesize that, under the same conditions, a genetic factor may
      predispose to this hair shaft defect.

PMID- 15953066
TI  - A survey of bathing and showering practices in children with atopic eczema.
AB  - We evaluated the emollient use and bathing habits of children with atopic eczema
      (AE) managed at the paediatric dermatology clinic of a university teaching
      hospital, using children with noneczematous skin diseases as controls. Disease
      severity of AE in the preceding 12 months was evaluated by the Nottingham Eczema
      Severity Score. Three-quarters of patients with or without eczema preferred
      showering to bathing. Patients with AE were more likely to use bath oils than
      soap and to use emollients after a bath/shower. Review cases, however, were more
      likely to take a shower and for a longer time (10-30 min) than first-visit eczema
      patients. These habits did not vary with season or disease severity. Emulsifying
      ointment was the most commonly used agent for the bath/shower. Most patients
      applied emollient immediately after a bath/shower. However there were still
      significant proportions of AE patients who used soap (40% of first-visit vs. 27%
      of review cases) and who did not apply emollients after a bath/shower (25% of
      first-visit vs. 23% of review cases). It is important to determine whether this
      problem is due to inadequate patient education or whether other factors lead to
      poor compliance.

PMID- 15953067
TI  - Brooke-Spiegler syndrome: treatment with laser ablation.
AB  - Brooke-Spiegler syndrome is a rare genetic condition associated with adnexal and
      epidermal tumours. Facial trichoepitheliomas and cylindromas are particularly
      distressing to sufferers. Conventional treatment can be followed by recurrence.
      We report a case with disfiguring trichoepithelioma treated with erbium:Yag and
      CO2 laser, achieving a good cosmetic result without recurrence after 2 years.
      Brooke-Spiegler syndrome and its treatment are reviewed.

PMID- 15953068
TI  - Metastatic Crohn's disease in a child.
AB  - Metastatic Crohn's disease is a rare complication of Crohn's disease that has not
      been frequently reported in the literature. Although Crohn's disease is common in
      children, cutaneous manifestations are rarely a presenting sign. We report the
      case of a young boy who initially presented with unusual skin lesions and whose
      condition was diagnosed later as Crohn's disease.

PMID- 15953069
TI  - Congenital facial linear porokeratosis.
AB  - We report a unique case of congenital linear porokeratosis with exclusive facial
      involvement in a 27-year-old Chinese man. No other family member was affected. To
      our knowledge, this is the first report in the English literature of congenital
      linear porokeratosis confined to the face.

PMID- 15953070
TI  - Identification of a recurrent mutation in the human hairless gene underlying
      atrichia with papular lesions.
AB  - Identification of mutations in the hairless (HR) gene in patients with atrichia
      with papular lesions (APL) has proven of critical importance, as it provides a
      basis for the differentiation between APL and alopecia universalis. The
      establishment of the diagnostic criteria for APL has triggered the identification
      of a large number of APL patients among those suspected to suffer from alopecia
      universalis. This advancement has resulted in the discovery of an increasing
      number of hairless mutations in both consanguineous and nonconsanguineous APL
      families. Here, we report the identification of a homozygous mutation, 3434delC,
      in an APL patient of Arab-Palestinian descent. The proband is a 23-year-old
      female with generalized scalp and body alopecia. To confirm the diagnosis of APL
      and to identify the specific mutation, we sequenced the hairless gene. Sequencing
      of all exons of the hairless gene revealed a homozygous frameshift mutation,
      3434delC, in exon 18. Interestingly, the same mutation was previously identified
      in an Arab-Israeli family. Our data suggest that the 3434delC mutation most
      likely represents a founder mutation in this geographical region.

PMID- 15953071
TI  - Streptococcus induced pustular vasculitis affecting the hands resembling pustular
      vasculitis of the hands--first reported case.
AB  - Pustular vasculitis of the hands is a distinctive clinical entity. It has
      recently been proposed by some authors to rename pustular vasculitis of the hands
      as 'neutrophilic dermatosis of the hands' to reflect its histological resemblance
      to the neutrophilic dermatoses. We report the case of a 66-year-old woman who
      presented with clinical appearances resembling pustular vasculitis of the hands
      associated with palmo-plantar pustulosis due to Streptococcus-induced 'pustular
      vasculitis'.

PMID- 15953072
TI  - A case of isolated cutaneous pseudo-inflammatory tumour.
AB  - Pseudo-inflammatory tumours are a poorly defined group of tumours, with
      indeterminate malignant potential, which can occur at almost any site of the
      body. The optimal treatment of inflammatory pseudo-tumours is yet to be
      elucidated. Surgical excision has been the most frequently reported treatment in
      the literature. We report a case of solitary cutaneous inflammatory pseudo
      tumour.

PMID- 15953073
TI  - Granuloma faciale treated with the pulsed-dye laser: a case series.
AB  - Granuloma faciale (GF) is a rare cutaneous condition of unknown origin with
      characteristic clinicopathological features. It predominantly affects the face
      and in some causes an unacceptable cosmetic appearance. Numerous medical and
      surgical treatments have been used with varying degrees of success. Several
      single-patient case reports have demonstrated the successful use of the pulsed
      dye laser (PDL) in treating GF. This study assesses the results of four patients
      with facial GF from one dermatological laser centre that were treated with the
      Candela Vbeam PDL at 595 nm. Resolution of the GF was achieved in only two of the
      four patients (50%). Nevertheless this study provides further evidence that the
      PDL can help some patients with GF. Subsequently it is still a valuable treatment
      option for GF, especially as it is safe, well tolerated and quick.

PMID- 15953074
TI  - Narrow-band UVB in the treatment of early stage mycosis fungoides: report of 16
      patients.
AB  - Although early stage mycosis fungoides (MF) has a generally good prognosis, and
      long-term survival rates with current therapies (UVB, photochemotherapy, topical
      nitrogen mustard, electron beam radiotherapy) are similar, there is concern
      regarding their potential side effects. It has been reported that the same
      effective UVB dose is safer than PUVA in terms of carcinogenicity, and that it
      produces fewer side effects. Our aim was to evaluate the effect of narrow-band
      UVB in the treatment of early stage MF. Sixteen patients (seven males, nine
      females; mean age, 40 years) with early stage MF received TL-01 phototherapy
      three times per week using a standard protocol. Twelve patients (75%) had
      complete response in a mean of 27.9 treatments, three had partial response, and
      one no response. Upon discontinuation of treatment, six patients with complete
      response relapsed in a mean time to relapse of 4.5 months. The present study
      indicates that narrow-band-UVB is an effective treatment modality for early stage
      MF.

PMID- 15953075
TI  - Treatment of small plaque parapsoriasis with narrow-band (311 nm) ultraviolet B:
      a retrospective study.
AB  - Narrow band (311 nm) ultraviolet B (NB-UVB) has been shown to be a safe and
      effective treatment for psoriasis and other inflammatory skin diseases. We have
      therefore employed NB-UVB in the treatment of small plaque parapsoriasis (SPP)
      since 1996. All patients (16/16) responded with complete remission of the disease
      after a mean number of 32.8 exposures and a mean total dose of 35.4 J/cm2.
      Unwanted side-effects were rare (3.3%) and always mild. Relapse of the disease
      occurred after an average of 29 weeks in those patients who came for follow-up
      visits. Therefore, NB-UVB is an effective, comparably safe and convenient
      alternative to psoralen and ultraviolet A therapy or other treatment modalities
      in the suppression of SPP.

PMID- 15953076
TI  - Two squamous cell carcinomas arising in a linear epidermal naevus in a 28-year
      old female.
AB  - The development of a squamous cell carcinoma (SCC) in a linear epidermal naevus
      is a rare event previously reported in long-standing and often extensive lesions
      of middle-aged to elderly patients. To the best of our knowledge, this case
      appears to be only the second report of an SCC arising in a linear epidermal
      naevus in a young patient and the first report of two SCCs developing in a small
      epidermal naevus, over a short time, in a young patient with no other risk
      factors.

PMID- 15953077
TI  - Composite cutaneous haemangioendothelioma: case report and review of the
      literature.
AB  - Composite cutaneous haemangioendothelioma is a recently characterized rare tumour
      of vascular origin. As there are only a few reported cases, the biological
      behaviour of the tumour and appropriate therapeutic approaches are not yet clear.
      We report a new case of composite cutaneous haemangioendothelioma and discuss
      prognostic and therapeutic aspects of this neoplasm.

PMID- 15953078
TI  - Nutritional deficiencies and the skin.
AB  - Malnutrition states are relatively uncommon in the UK but we have seen two recent
      cases which have heightened our awareness of both dermatological manifestations
      of malnutrition and of nutritional sequelae of a dermatological problem. Case 1
      is a patient with anorexia nervosa presenting with features of pellagra. This
      condition is due to deficiency of niacin and responds rapidly to replacement
      therapy. Classical presentation is an erythematous rash on photoexposed sites,
      often related to heat or friction. There are three reported cases of pellagra
      occurring in patients with anorexia nervosa. Case 2 is an adult atopic with
      sensitizations to multiple foodstuffs. A self-imposed restriction diet caused
      multiple nutritional deficiencies. Restriction diets in adult atopics are not
      particularly common in the UK, but there is some evidence to suggest that they
      may cause significant nutritional deficiency. A nutrition screen may be indicated
      more frequently than is currently recognized.

PMID- 15953079
TI  - Unusual cutaneous involvement during plasma cell leukaemia phase in a multiple
      myeloma patient after treatment with thalidomide: a case report and review of the
      literature.
AB  - We report the case of a 54-year-old African-American male with IgG multiple
      myeloma (MM) with disease resistant to multiple chemotherapy regimens and
      immunomodulatory treatment with thalidomide. In spite of achieving a partial
      remission of short duration, his disease accelerated to peripheral plasmacytosis
      and subsequent development of cutaneous plasmacytomas. The malignant plasma cells
      derived from the dermal lesions were CD45+, CD38+, CD138+ and matched the
      immunophenotype of the plasmacytes during the leukaemic phase. Occurrence of
      extramedullary lesions in the setting of MM treated with thalidomide is of
      concern, although currently there are very few reports describing this
      association. We discuss the possible relationship between the patient's unusual
      disease course and the administered chemo- and immunotherapy. The significance of
      the changes in adhesion molecules, especially CD138 and CD56, relevant to the
      development of cutaneous plasmacytomas is discussed.

PMID- 15953080
TI  - Disseminated Kaposi's sarcoma associated with idiopathic CD4+ lymphocytopenia and
      low dose steroid therapy.
AB  - A case of disseminated Kaposi sarcoma in a 76-year-old woman treated with low
      dose steroids for a seronegative polyarthritis is described. HIV serology was
      negative, whereas PCR for HHV-8 was positive. The patient presented with a
      profound reduction in the peripheral blood CD4+ cell count and a decrease in
      serum immunoglobulins and was diagnosed as having idiopathic CD4+
      lymphocytopenia. The clinical picture was characterized by limited cutaneous
      lesions with typical features of KS associated with widespread visceral
      involvement and unusually aggressive behaviour.

PMID- 15953081
TI  - The alpha-3 polypeptide chain of laminin 5: insight into wound healing responses
      from the study of genodermatoses.
AB  - Laminin 5 (kalinin/epiligrin/nicein) is an essential structural component of the
      dermal-epidermal junction, composed of three polypeptide subunits: laminin
      alpha3, beta3 and gamma2. Studies of the inherited skin fragility disorder
      junctional epidermolysis bullosa (JEB) have suggested that the major role of this
      heterotrimeric protein is to act as an adhesive ligand essential for binding the
      epidermis to the underlying dermis and thus maintaining the integrity of the
      skin. Protein interaction studies have shown that the C terminus of the alpha3
      subunit binds to a range of integrin complexes depending on the motility status
      of keratinocytes. This allows laminin 5 to interact with either hemidesmosomes or
      the actin cytoskeleton. Recently we have reported that the absence of the N
      terminal region of laminin alpha3a in laryngo-onchyo-cutaneous syndrome causes
      excessive granulation tissue production at wound sites. As granulation tissue
      production is also a problem in JEB, this implicates laminin 5 in control of this
      wound healing response.

PMID- 15953082
TI  - Rheumatoid factor isotypes in localized scleroderma.
AB  - Localized scleroderma is a connective tissue disorder that is sometimes
      accompanied by various immunological abnormalities. In this study, we analysed
      serum levels of rheumatoid factor (RF) isotypes in patients with localized
      scleroderma and in normal controls to determine if any of these isotypes reflect
      the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%,
      and 7% of the patients, respectively. The levels of IgM RF were significantly
      higher in the patients with generalized morphea (GM), the most severe form of
      localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or
      normal controls (P < 0.0005). The levels of IgG RF were significantly higher in
      patients with GM than normal controls (P < 0.05). The levels of IgA RF were
      significantly higher in patients with GM or LS than normal controls (P < 0.001
      and P < 0.01, respectively). The count of sclerotic lesions was significantly
      higher in patients with IgM RF than those without (P < 0.05). These results
      suggest that the presence of RF isotypes is one of the immunological
      abnormalities of localized scleroderma. IgM RF seemed to be most useful of these
      three factors to determine the severity of disease.

PMID- 15953083
TI  - Electrical measurement of moisturizing effect on skin hydration and barrier
      function in psoriasis patients.
AB  - Transepidermal water loss (TEWL) in psoriatic skin lesions seems to be related to
      the severity of the psoriasis, and the electrical capacitance and conductance of
      the skin are indicators of the hydration level of the stratum corneum. We
      compared the characteristics of these electrical measurements, in assessing the
      persistent effect of a moisturizing cream on skin hydration and barrier function
      in psoriasis patients. Seventeen Korean psoriasis patients were recruited. Their
      right leg was treated with the moisturizer twice daily for 6 weeks, while their
      left leg was used as the control site. For each patient, one psoriatic plaque on
      each leg was selected as the involved psoriatic lesion. Uninvolved psoriatic skin
      was regarded as the apparently healthy looking skin 4-5 cm away from the
      periphery of the psoriatic lesion. The TEWL, electrical capacitance and
      conductance were measured, in order to evaluate the barrier function and
      hydration level of the stratum corneum. The clinical and biophysical data for
      each patient were recorded at the start of the study and after 2, 4 and 6 weeks.
      The degree of skin dryness at the applied area improved progressively. The
      electrical capacitance at the treated psoriatic lesion increased significantly
      after 2 weeks, and this improvement was maintained during the entire study
      period. However, no noticeable change was observed in the electrical conductance.
      The TEWL showed an inverse pattern to that of the skin capacitance, decreasing
      during the study period. The skin capacitance and TEWL exhibited good correlation
      with the visual assessment of skin dryness, but the skin conductance did not. Our
      data suggest that electrical capacitance and TEWL may be useful in the evaluation
      of the effect of a moisturizer on the hydration status and barrier function of
      psoriatic skin.

PMID- 15953084
TI  - Corneodesmosin (CDSN) gene association with psoriasis vulgaris in Caucasian but
      not in Japanese populations.
AB  - PSORS1 on chromosome 6p21.3, which contains the MHC, is a major susceptibility
      locus for psoriasis vulgaris. This region is characterized by strong linkage
      disequilibrium and contains the corneodesmosin (CSDN) gene, an attractive
      candidate for psoriasis susceptibility based on its putative biological function
      in keratinocyte adhesion, and HLA-Cw6, an established marker for psoriasis
      susceptibility. We compared two genetically independent populations in order to
      define the major psoriasis susceptibility gene, a British Caucasian population
      comprising parent-offspring trios analysed by the transmission disequilibrium
      test (TDT) and a Japanese case-control population. All individuals were
      investigated for CDSN polymorphism (+619, +1236, +1240 and +1243) and HLA-C
      association. Our data confirms strong association with HLA-Cw6 and CDSN allele 5
      (+619T, +1240G, +1243C) in the Caucasian cohort (TDT, P = 5.4 x 10(-6)) and in
      addition defines this region further by identifying a high-risk CDSN haplotype
      (allele 5 and +1236T, P = 8.5 x 10(-8)). In contrast no association was observed
      in the Japanese cohort for any HLA-C or CDSN alleles. This data supports a role
      for the CDSN gene in Caucasian populations with psoriasis. However the lack of
      association with HLA-Cw6 and CDSN alleles in Japanese psoriasis patients may be
      because Japanese patients exhibit a form of psoriasis similar to late onset or
      Type II psoriasis vulgaris in contrast to early onset or Type I disease
      characterizing our Caucasian population.

PMID- 15953085
TI  - Two novel frameshift mutations of the EBP gene in two unrelated Thai girls with
      Conradi-Hunermann-Happle syndrome.
AB  - Conradi-Hunermann-Happle syndrome, also known as X-linked dominant
      chondrodysplasia punctata (CDPX2), is characterized by skeletal abnormalities,
      cutaneous anomalies and cataracts. CDPX2 is caused by mutations in the emopamil
      binding protein (EBP). We report two unrelated Thai female patients with
      clinically typical CDPX2, in which we discovered two novel and de novo frameshift
      mutations: 506-507delAG and 540-541delCC. This study demonstrates that EBP is the
      gene responsible for CDPX2 across different populations and extends the total
      number of confirmed mutations to 55.

PMID- 15953086
TI  - HLA-G expression in basal cell carcinomas of the skin recurring after
      radiotherapy.
AB  - Basal cell carcinoma (BCC) of the skin represents the most common malignancy in
      the fair-skinned population worldwide. HLA-G is one of the molecules implicated
      in immunotolerance. To investigate the role of HLA-G in recurring BCCs, we
      constructed a tissue microarray containing 38 primary BCCs that underwent
      radiotherapy and 14 secondary BCCs recurring on the primary site after
      radiotherapy, and evaluated the HLA-G protein expression by immunohistochemistry.
      The HLA-G protein was most frequently expressed in aggressive sclerosing BCCs.
      Nodular BCC demonstrated the strongest HLA-G expression. Interestingly, tumor
      infiltrating mononuclear cells (TIMC) expressed the HLA-G molecule in BCCs that
      showed no recurrence. After comparing primary BCCs and BCCs relapsed after
      radiotherapy, we observed decreased HLA-G expression on tumor cells and the loss
      of HLA-G expression on TIMC in relapsed BCCs. After radiotherapy, immunobiology
      of BCC may change resulting in the down-regulation of HLA-G expression on tumor
      and on tumor-infiltrating cells.

PMID- 15953087
TI  - Cytokeratin expression in pili annulati hair follicles.
AB  - Pili annulati is a rare autosomal inherited hair shaft abnormality of unknown
      pathogenesis in which clinical examination reveals alternating light and dark
      bands leading to a shiny appearance of the hair due to cavities within the cortex
      of the hair shaft. This is the first investigation of the proposed cytokeratin
      defect in pili annulati hair follicles. Four cryopreserved pili annulati and four
      control scalp specimens were analysed using immunohistochemistry for different
      'hard' trichocytic and 'soft' epithelial cytokeratins including K1, K6, K10, K14,
      K16, K17, K18, K19, Ha1 and Hb1. There was no difference in staining intensity
      and quality of staining pattern seen in pili annulati and control scalp
      specimens. These results suggest that pili annulati is not caused by a defect of
      the cytokeratins investigated in this study.

PMID- 15953088
TI  - Structural, enzymatic and molecular studies in a series of nonbullous congenital
      ichthyosiform erythroderma patients.
AB  - Causative gene defects have not been demonstrated in the majority of nonbullous
      congenital ichthyosiform erythroderma (NBCIE) cases. The purpose of this study
      was to further elucidate the pathogenesis of NBCIE. Immunohistochemical and
      ultrastructural observations, transglutaminase activity assays and sequencing of
      TGM1 were performed in five patients from four NBCIE families. Transglutaminase 1
      (TGase 1), involucrin and loricrin expression and in situ transglutaminase
      activity were present in all of the cases. Ultrastructurally, two cases out of
      five showed incomplete thickening of the cornified cell envelope (CCE) during
      keratinization and the other three exhibited abnormal lipid droplets in the
      cornified cells and malformed lamellar granules. No TGM1 mutation was found in
      any of the four families by direct sequence analysis. NBCIE cases with normal
      TGase 1 seemed to have two distinct patterns of abnormality, one with abnormal
      lipid droplets and malformed lamellar granules and the other with defective CCE
      formation.

PMID- 15953090
TI  - Magnetic resonance imaging in eosinophilic fasciitis.

PMID- 15953089
TI  - In vitro cytokine profile in childhood alopecia areata and the immunomodulatory
      effects of AS-101.
AB  - The aim of the present study was to determine the effect of AS-101, a known
      immunomodulator, on the pattern of cytokine production in children with patchy
      alopecia areata (PAA). Ten previously untreated children with PAA were compared
      to 10 healthy age- and sex-matched controls. Peripheral blood mononuclear cells
      (PBMC) were isolated from all participants. Unstimulated and phytohaemagglutinin
      (PHA)-stimulated PBMC were tested with and without the addition of AS-101. The
      production of interferon gamma (IFNgamma), soluble interleukin (IL)-2 receptor
      (IL-2R), IL-10, IL-5 and IL-6 was determined. The levels of soluble IL-2R, IL-5
      and IL-6 were significantly higher in the PAA patients than the controls. AS-101
      inhibited the production of IL-10, IFNgamma, IL-2R and IL-5 in both PAA patients
      and controls, but there was a greater inhibitory effect in children with PAA.

PMID- 15953091
TI  - Successful treatment of severe atopic dermatitis with methotrexate.

PMID- 15953092
TI  - Facial acanthosis nigricans associated with obesity.

PMID- 15953093
TI  - Lipoma of the finger: a case report and differential diagnosis.

PMID- 15953094
TI  - An unusual distribution of cutaneous metastases of ovarian carcinoma.

PMID- 15953095
TI  - A case of otophyma.

PMID- 15953096
TI  - Pityriasis rubra pilaris as the initial presentation of renal cell carcinoma?

PMID- 15953097
TI  - Basal cell carcinoma in a leishmanial scar.

PMID- 15953098
TI  - Koebnerization of donor site in unilateral vitiligo patients, treated
      successfully by autologous, noncultured melanocyte-keratinocyte (MK) cell
      transplantation.

PMID- 15953099
TI  - Woringer-Kolopp (localized pagetoid reticulosis) treated with topical
      photodynamic therapy (PDT).

PMID- 15953100
TI  - Tear gas dermatitis.

PMID- 15953101
TI  - Hereditary haemorrhagic telangiectasia associated with vitiligo, autoimmune
      thyroiditis, iridocyclitis and a myelodysplastic syndrome.

PMID- 15953102
TI  - Topical tacrolimus in the treatment of annular erythema associated with Sjogren's
      syndrome.

PMID- 15953103
TI  - Comparable effects of sildenafil citrate and alprostadil on severe Raynaud's
      phenomenon in a patient with systemic sclerosis.

PMID- 15953104
TI  - Lichen nitidus and lichen spinulosus or spinous follicular lichen nitidus?

PMID- 15953105
TI  - A positive correlation between history of psoriasis response to sunlight and the
      response to UVB phototherapy. What are the consequences?

PMID- 15953106
TI  - Wet wraps in atopic eczema: the dangers of inadequately sized 'negative' clinical
      trials.

PMID- 15953109
TI  - A review of recent journal highlights.

PMID- 15953110
TI  - C1 inhibitor deficiency: diagnosis.
AB  - This is the first of two articles on C1 inhibitor deficiency based on a recent UK
      consensus document covering diagnosis and management of the disorder in both
      adults and children. This paper focuses on diagnosis of this disorder.

PMID- 15953111
TI  - An iatrogenic dermatosis with ulceration.

PMID- 15953112
TI  - An uncommon mimic of a common condition.

PMID- 15953113
TI  - Aberrations and myopia.
AB  - It has been suggested that high levels of axial aberration or specific patterns
      of peripheral refraction could play a role in myopia development. Possible
      mechanisms involving high levels of retinal image blur caused by axial
      aberrations include form deprivation through poor retinal image quality in
      distance vision, enhanced accommodative lags favouring compensatory eye growth,
      and an absence of adequate directional cues to guide emmetropization. In
      addition, in initially emmetropic eyes, hyperopia in the retinal periphery may
      result in local compensatory eye growth, which induces axial myopia. Evidence in
      support of these ideas is reviewed and it is concluded that, for any fixed pupil
      diameter, evidence for higher levels of axial aberration in myopes in comparison
      with other refractive groups is weak, making involvement of axial aberrations in
      myopization through image degradation at the fovea unlikely. If, however, some
      potential myopes had unusually large pupil diameters, their effective aberration
      levels and associated retinal blur would be larger than those of the rest of the
      population. There is stronger evidence in favour of differences in patterns of
      peripheral refraction in both potential and existing myopes, with myopes tending
      to show relative hyperopia in the periphery. These differences appear to be
      related to a more prolate eyeball shape. Longitudinal studies are required to
      confirm whether the retinal defocus associated with the peripheral hyperopia can
      cause patterns of eyeball growth which lead to axial myopia.

PMID- 15953114
TI  - Refractive error and ocular biometry in Jordanian adults.
AB  - The aim of this study was to establish the prevalence of refractive errors in
      Jordanian adults of working age, and to study the ocular biometric correlates of
      refractive error in this population. Refractive error and ocular biometry were
      measured in 1093 Jordanian adult subjects aged 17-40 years to determine the
      prevalence of refractive error, and explore structural correlations of ametropia.
      Refractive error was measured using a Grand-Seiko GR-3100K closed-view infrared
      autorefractor. Ocular component measurements were made using A-scan
      ultrasonography and autokeratometry. The prevalence of myopia [spherical
      equivalent refraction (SER) less than -0.50 DS] and hyperopia (SER greater than
      +0.50 DS) was 53.71 and 5.67% respectively; 40.62% of the sample was emmetropic
      (refraction between +0.50 D and -0.50 D inclusive in both principal meridians).
      The distribution of SER was found to show marked leptokurtosis, exhibiting a peak
      between plano and 1 D of myopia. Corneal radius, anterior chamber depth,
      crystalline lens thickness, vitreous chamber depth and axial length (AL)
      parameters were normally distributed in the population studied. AL to corneal
      curvature ratio was not normally distributed, and showed marked leptokurtosis.
      Linear regression analysis showed that AL correlated most closely with spherical
      equivalent refractive error. This study has established a database of refractive
      error prevalence and ocular biometric correlates of ametropia in a Middle Eastern
      population of working age.

PMID- 15953115
TI  - Downward deviation of progressive addition lenses in a myopia control trial.
AB  - PURPOSE: To clarify how the downward deviation of progressive addition lenses
      (PALs) reduces their near-addition effect in schoolchildren participating in a
      myopia control trial. METHODS: Among 95 schoolchildren wearing PALs for 6 months
      (age range: 6-12 years; refractive error range: -6.00 to -1.25 D), facial images
      were captured with a digital still camera placed 60 cm in front of the eyes while
      he or she was looking ahead with natural head posture. The vertical deviations of
      PALs from their ideal position (mm) were evaluated by analysing these images.
      RESULTS: The mean (+/-SD) downward deviations of PALs for the right and left eyes
      were 3.7 +/- 2.3 and 3.7 +/- 2.0 mm, respectively, and the largest downward
      deviation was 10.2 mm. For simulations using the average downward deviation, the
      near-addition effect of PALs was reduced to 30 and 63% of the expected value at
      the 10 degrees and 20 degrees downward eye positions, respectively. CONCLUSIONS:
      The downward deviation of PALs is a significant factor in reducing their
      therapeutic effect for near-addition. To ensure the proper alignment of PALs in
      children, the conventional spectacle-frame-fitting procedure is not sufficient,
      and repeated confirmation using a testing method similar to that used in this
      study is required.

PMID- 15953116
TI  - CFF thresholds: relation to macular pigment optical density.
AB  - PURPOSE: Only two small studies have evaluated the relation between individual
      differences in macular pigment (MP) levels and visual health prior to retinal
      disease. In this study, we assess the relation between MP and a general measure
      of visual health, the critical flicker fusion (CFF) threshold. METHODS: A total
      of 134 subjects were assessed. CFF values were determined psychophysically using
      a 570 nm, circular 1-degree test field centrally fixated. MP optical density was
      measured using flicker photometry and a 1-degree circular 458 nm test field
      centrally fixated. Personal characteristics were determined by questionnaire.
      RESULTS: Similar to past studies, we found a significant decline in CFF values
      with age (r = -0.56). There was a significant positive relationship (r = 0.30, p
      < 0.001) between MP density and CFF values that was independent of age.
      CONCLUSIONS: These results are consistent with a protective effect of MP on
      visual health across the lifespan.

PMID- 15953117
TI  - The effect of apparent depth in pictorial images on accommodation.
AB  - The purpose of this study was to investigate the effect of the apparent depth of
      pictorial images on accommodation. Steady-state accommodation was assessed
      objectively while viewing eight pictorial stimuli containing varying degrees of
      monocular cues to depth. Sixteen young adult subjects were tested monocularly
      with accommodation either in the closed-loop or open-loop mode. Pictorial depth
      cues significantly influenced the mean level of accommodation under some of the
      open-loop conditions in which blur feedback was rendered ineffective. For nearly
      all stimuli and viewing modes, the mean accommodative responses were biased in
      the perceptually-appropriate direction, but they were larger in the open-loop
      condition. Apparent depth cues did not significantly affect accommodation under
      closed-loop viewing conditions, presumably because blur feedback markedly
      dampened any perceptually-driven influences. Consistent with current models of
      accommodation, and several earlier studies, perceptually-based accommodation had
      only a secondary effect on the overall accommodative response level under
      naturalistic viewing conditions, with blur dominating.

PMID- 15953118
TI  - Characteristics of pupil responses during far-to-near and near-to-far
      accommodation.
AB  - The static and dynamic aspects of the pupil response associated with various
      amplitudes of far-to-near (accommodation) and near-to-far (disaccommodation)
      focusing responses were evaluated in this study. Dynamic refractive and pupillary
      changes were measured simultaneously during focusing responses to targets at real
      distances in 12 young (23-26 years) emmetropic subjects. The targets were
      presented alternately at far (6 m) and at one of six near positions from 1 D (1
      m) to 6 D (16.7 cm) in 1 D steps. The latency, magnitude and peak velocity of
      pupil changes associated with accommodation and disaccommodation responses were
      calculated. The latency of refractive changes was shorter than that of pupillary
      changes. In general, the pupil constricted with accommodation and started
      dilating while accommodation was still maintained, resulting in reduced pupil
      dilation with disaccommodation. The magnitude of the pupil response increased
      linearly with that of accommodation and disaccommodation. The amount of pupil
      change per dioptre of refractive change was invariant with various amplitudes of
      refractive change. The peak velocity of pupil constriction was greater than that
      of pupil dilation for corresponding amplitudes. The pupil response is more
      closely associated with accommodation than with disaccommodation.

PMID- 15953119
TI  - The influence of cycloplegia in objective refraction.
AB  - The purpose of this study was to compare refractions measured with an
      autorefractor and by retinoscopy with and without cycloplegia. The objective
      refractions were performed in 199 right eyes from 199 healthy young adults with a
      mean age of 21.6 +/- 2.66 years. The measurements were performed first without
      cycloplegia and repeated 30 min later with cycloplegia. Data were analysed using
      Fourier decomposition of the power profile. More negative values of component M
      and J(0) were given by non-cycloplegic autorefraction compared with cycloplegic
      autorefraction (p < 0.0001). However more positive values for the J(45) vector
      were given by non-cycloplegic autorefraction, although this difference was not
      statistically significant (p = 0.233). By retinoscopy, more negative values of
      component M were obtained with non-cycloplegic retinoscopy (p < 0.0001); for the
      cylindrical vectors J(0) and J(45) the retinoscopy without cycloplegia yields
      more negative values (p = 0.234; p = 0.112, respectively). Accepting that
      differences between cycloplegic and non-cycloplegic retinoscopy are only due to
      the accommodative response, the present results confirm that when performed by an
      experienced clinician, retinoscopy is a more reliable method to obtain the
      objective starting point for refraction under non-cycloplegic conditions.

PMID- 15953120
TI  - Eye fixation scanpaths of younger and older drivers in a hazard perception task.
AB  - Our previous research has shown that observing patterns of eye fixations is a
      successful method of establishing differences in underlying cognitive processes
      between groups of drivers. Eye movements recorded from drivers in a laboratory
      while they watch film clips recorded from a driver's perspective can be used to
      identify scanpaths and search patterns that reveal ability differences. In the
      present study 12 older subjects (60-75 years) and 12 younger subjects (30-45
      years) watched clips for potential hazards such as other road users appearing on
      an intersecting trajectory. Acuity and visual field differences between the two
      groups were eliminated through screening, so that only age-related differences
      would emerge. Eye fixations were analysed on a frame-by-frame basis to generate
      sequences of codes representing the location and object of the viewer's interest,
      before and during the appearance of a hazard. These codes were analysed for the
      existence of two fixation scanpaths using Markov Matrices. Unique scanpaths were
      identified for each group of drivers before and during the hazard. Evidence from
      the inspection of different objects and from the spread of the search indicated
      that both groups of driver were sensitive to attentional capture by the
      appearance of the hazard. Detection of the hazards - both speed and accuracy -
      was similar for older and younger drivers, although the older drivers perceived
      the films as being more hazardous in general. There is little evidence in this
      study of an age-related decline in the search of the scene when detecting
      hazards.

PMID- 15953121
TI  - Optometric and ophthalmic contact in elderly hip fracture patients with visual
      impairment.
AB  - AIM: To describe previous contact with optometry and ophthalmic services in a
      group of elderly patients with and without visual impairment (VI) who had fallen
      and sustained a fractured neck of femur. METHOD: A cross sectional study of 537
      patients aged 65 and over who had undergone hip fracture surgery in four Scottish
      centres (Glasgow, Ayr, Dundee and Fife). All patients had an in-depth optometric
      history, ophthalmic history and examination. RESULTS: Three hundred and ninety
      three (79%) patients reported optometric contact in the 3 years preceding surgery
      and 107 (21%) patients had not seen an optometrist for more than 3 years. In the
      latter group, 64 had VI, which was due to uncorrected refractive error in 17
      (27%) and untreated cataract in 20 (31%). VI (best binocular visual acuity of
      6/18 or less) was found in 239 (46%) patients. A past ophthalmic history was
      present in 257 (50%) patients. Only 39 (16%) patients with VI were under
      ophthalmic care at the time of the study. CONCLUSIONS: There was significantly
      poor optometric and ophthalmic contact in patients who had VI and had fallen and
      sustained hip fracture. A proportion of the VI (66%) was due to uncorrected
      refractive error and untreated cataract. Public health providers should be made
      aware of the fact that current optometric and ophthalmic care pathways are not
      accessed by this group of elderly patients with VI and at risk of falling.

PMID- 15953122
TI  - The need for optometric investigation in suspected Meares-Irlen syndrome or
      visual stress.
AB  - Meares-Irlen syndrome is characterised by symptoms of eye strain, headaches and
      visual perceptual distortions when viewing text. The symptoms are alleviated with
      individually prescribed coloured filters, such as precision tinted lenses. Meares
      Irlen syndrome, and the related condition of visual stress, are likely to result
      from hyperexcitability of the visual cortex, which can also occur in migraine.
      The symptoms of Meares-Irlen syndrome and visual stress are non-specific and the
      condition needs to be differentially diagnosed from other optometric conditions,
      such as refractive error, binocular vision anomalies, and accommodative
      anomalies. Three case reports are described of patients who consulted the author
      with suspected Meares-Irlen syndrome but were found to have other causes for
      their symptoms: posterior sub-capsular cataract, high uncorrected astigmatism,
      and decompensated convergence weakness exophoria. These cases highlight the need
      for professional eye care for people with suspected Meares-Irlen syndrome.
      Although this advice is stressed in literature on the well-established
      MRC/Wilkins Intuitive Colorimeter system, it is not always stressed in literature
      about other systems. This may be a cause for concern.

PMID- 15953123
TI  - Evaluation of Melbourne Edge Test contrast sensitivity measures in the visually
      impaired.
AB  - AIM: Contrast sensitivity (CS) provides important information on visual function.
      This study aimed to assess differences in clinical expediency of the CS increment
      matched new back-lit and original paper versions of the Melbourne Edge Test (MET)
      to determine the CS of the visually impaired. METHODS: The back-lit and paper MET
      were administered to 75 visually impaired subjects (28-97 years). Two versions of
      the back-lit MET acetates were used to match the CS increments with the paper
      based MET. Measures of CS were repeated after 30 min and again in the presence of
      a focal light source directed onto the MET. Visual acuity was measured with a
      Bailey-Lovie chart and subjects rated how much difficulty they had with face and
      vehicle recognition. RESULTS: The back-lit MET gave a significantly higher CS
      than the paper-based version (14.2 +/- 4.1 dB vs 11.3 +/- 4.3 dB, p < 0.001). A
      significantly higher reading resulted with repetition of the paper-based MET (by
      1.0 +/- 1.7 dB, p < 0.001), but this was not evident with the back-lit MET (by
      0.1 +/- 1.4 dB, p = 0.53). The MET readings were increased by a focal light
      source, in both the back-lit (by 0.3 +/- 0.81, p < 0.01) and paper-based (1.2 +/-
      1.7, p < 0.001) versions. CS as measured by the back-lit and paper-based versions
      of the MET was significantly correlated to patients' perceived ability to
      recognise faces (r = 0.71, r = 0.85 respectively; p < 0.001) and vehicles (r =
      0.67, r = 0.82 respectively; p < 0.001), and with distance visual acuity (both r
      = -0.64; p < 0.001). CONCLUSIONS: The CS increment-matched back-lit MET gives
      higher CS values than the old paper-based test by approximately 3 dB and is more
      repeatable and less affected by external light sources. Clinically, the MET score
      provides information on patient difficulties with visual tasks, such as
      recognising faces.

PMID- 15953124
TI  - The morphometric analysis of the central retinal artery.
AB  - In this study, we aimed to investigate some features of the central retinal
      artery (CRA), which supplies the internal aspect of the retina. The CRA is the
      main vessel supplying blood to the retina. The origin, course and penetration
      point of the optic nerve by the CRA were studied in 30 human orbits. We compared
      the right sides to the left sides on the basis of gender in order to
      statistically analyse the relation between them. The CRA arose directly from the
      ophthalmic artery in 28 specimens. In two specimens, however, it arose in common
      with the medial posterior ciliary artery. When we observed the penetration point
      (site) of the CRA into the optic nerve, in 28 of 30 (93.3%) cases, the artery
      entered the nerve from the lower medial aspect and in two (6.7%) cases from the
      upper lateral aspect. The CRA penetrated the optic nerve between 6.4 and 15.2 mm
      behind the eyeball and reached the eyeball through the centre of the optic nerve.
      Because of the small diameter of the artery, it has a high risk of getting
      damaged during a surgical approach to the orbit. Therefore the anatomical
      relationships of this artery must be well known.

PMID- 15953127
TI  - End-stage renal disease--not an equal opportunity disease: the role of genetic
      polymorphisms.
AB  - Despite several decades of development in renal replacement therapy, end-stage
      renal disease (ESRD) patients continue to have markedly increased morbidity and
      mortality especially caused by cardiovascular disease (CVD). This shows that
      current strategies, e.g. the focus on dialysis adequacy, to improve the clinical
      outcome in ESRD patients have to be complemented by novel approaches. Although
      traditional risk factors are common in dialysis patients they cannot alone
      explain the unacceptably high prevalence of CVD in this patient group. Much
      recent interest has therefore focused on the role of various nontraditional
      cardiovascular risk factors, such as inflammation, vascular calcification and
      oxidative stress. Recent studies show that genetic factors, such as DNA single
      nucleotide polymorphisms, may significantly influence the immune response, the
      levels of inflammatory markers, as well as the prevalence of atherosclerosis in
      this patient group. To elucidate the respective roles of DNA polymorphisms in
      genes that encode inflammatory markers (such as IL-10, IL-6 and TNF-alpha) and
      other factors that may affect the development of atherosclerosis (such as
      apolipoprotein E, transforming growth factor and fetuin-A), sufficiently powered
      studies are needed in which genotype, the protein product and the specific
      phenotype all are analysed in relation to outcome. The recent developments in the
      field of genetics have opened up entirely new possibilities to understand the
      impact of genotype on disease development and progress and thus offer new options
      and strategies for treatment. It seems conceivable that in the near future,
      prognostic or predictive multigene DNA assays will provide the nephrological
      community with a more precise approach for the identification of "high-risk" ESRD
      patients and the development of accurate individual treatment strategies. For
      this purpose, integrative studies on genotype-phenotype associations and impact
      on clinical outcome are needed.

PMID- 15953128
TI  - Low level of tissue plasminogen activator activity in non-diabetic patients with
      a first myocardial infarction.
AB  - OBJECTIVE: To explore the role of tissue plasminogen activator (tPA) activity and
      plasminogen activator inhibitor type 1 (PAI-1) in survivors of a first myocardial
      infarction (MI). Insulin and proinsulin were analysed as potential risk factors.
      DESIGN: Case-control study in northern Sweden. SUBJECTS: A total of 115 patients
      under 65 years of age with a first MI were enrolled and recalled for further
      examination 3 months later. Twenty-seven patients were excluded, 17 with known
      diabetes and 10 who did not come to the follow-up, giving a final number of 88
      patients, 73 men and 15 women. Patients were age- and sex-matched with control
      subjects drawn from the local cohort in the MONICA population survey 1994. MAIN
      OUTCOME MEASURES: We compared MI patients and controls using univariate and
      multiple regression analyses including odds ratios (OR). RESULTS: PAI-1 activity,
      fibrinogen, postload insulin and -proinsulin were significantly higher and tPA
      activity significantly lower in MI patients in the univariate analysis. In a
      multiple regression analysis, including also age, sex and cardiovascular risk
      factors, these parameters were divided in quartiles. The lowest quartile of tPA
      activity was significantly associated with MI (OR = 19.1; CI 3.0-123) together
      with the highest quartiles of fibrinogen (OR = 25; CI 5.2-120) but other
      variables were not. CONCLUSION: Low tPA activity, i.e. low fibrinolytic activity,
      characterized nondiabetic subjects after a first MI which is not explained by
      concomitant disturbances in metabolic and anthropometric variables.

PMID- 15953129
TI  - Effect of the Toll-like receptor 4 (TLR-4) variants on intima-media thickness and
      monocyte-derived macrophage response to LPS.
AB  - OBJECTIVES: Toll-like receptor 4 (TLR-4) is believed to contribute to the
      initiation and progression of atherosclerosis. The association of the D299G
      polymorphism of the TLR-4 gene with the progression of coronary and carotid
      atherosclerosis, risk of cardiovascular events and myocardial infarction is
      controversial. We have investigated whether the presence of the D299G
      polymorphism and the co-segregated T399I polymorphism affects the intima-media
      thickness (IMT) in the general population. SUBJECTS: The PLIC study population (n
      = 1256) was genotyped for the D299G and the T399I polymorphisms. RESULTS: The
      presence of both the D299G and T399I alleles was observed in the 13.0% of the
      population, carriers of the T399I alone were 1.8% and of the D299G alone were
      0.9%. No difference in IMT was detected within the carriers of the D299G and
      T399I alleles and the wild-type subjects in the PLIC population. Furthermore, we
      investigated whether monocyte from D299G to T399I subjects present a defective
      response to CD40, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, cyclo
      oxygenase (COX)-2 and PTX3 expression induced by lipopolysaccharide (LPS). When
      the monocyte-derived macrophages of these subjects were challenged with LPS (1
      mug mL(-1)), no impact of the polymorphisms on the induction of CD40, MCP-1 and
      PTX3 was observed. Only IL-6 and COX-2 induction by LPS resulted reduced in the
      D299G/T399I carriers. CONCLUSION: The presence of the D299G and T399I
      polymorphisms of the TLR-4 gene does not play a major role on the progression of
      carotid atherosclerosis. Macrophages from the subjects carrying the polymorphisms
      show an impaired response to LPS limited only to a IL-6 and COX-2.

PMID- 15953130
TI  - The metabolic syndrome in middle-aged men according to different definitions and
      related changes in carotid artery intima-media thickness (IMT) during 3 years of
      follow-up.
AB  - OBJECTIVES: To examine the occurrence over time of the metabolic syndrome (MetS)
      according to different definitions and the relation to change during follow-up in
      carotid artery intima-media thickness (IMT), measured by ultrasound. DESIGN: A
      cohort of 316, originally 58-year-old men, initially free of diabetes and
      cardiovascular disease, was followed for 3.2 +/- 0.2 years. IMT was measured
      bilaterally by high-resolution B-mode ultrasound at baseline and follow-up. The
      MetS was classified according to slightly modified World Health Organization
      (WHO) and National Cholesterol Education Program (NCEP) criteria. RESULTS: In 88%
      WHO and NCEP definitions resulted in identical classifications. IMT was larger
      both at baseline and after 3 years in men fulfilling the criteria for the MetS,
      according to either of the definitions, compared to those without factors in the
      syndrome. Men who fulfilled the WHO criteria for the MetS, at the initial and
      final examination showed a statistically significant increase in carotid artery
      IMT during the study [76 (95% CI: 14-130) microm, n = 37]. Men fulfilling the WHO
      criteria for the MetS at baseline tended to have a larger annual increase in IMT
      than those not fulfilling the criteria or having no risk factors in the syndrome.
      CONCLUSIONS: More than 10% of the men had the MetS both at baseline and after 3
      years, and this was associated with an increase in IMT using the WHO definition.
      Several of the components included in the MetS deteriorated during follow-up,
      i.e. body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, blood
      glucose and blood pressure.

PMID- 15953131
TI  - Pulse pressure is independently associated with sensorimotor peripheral
      neuropathy in patients with type 2 diabetes.
AB  - OBJECTIVES: The mechanisms responsible for the onset and progression of
      sensorimotor peripheral neuropathy (SMPN) in type 2 diabetes remain largely
      unknown. Although a link between hypertension and SMPN has been observed, it is
      not clear which blood pressure (BP) component (i.e. systolic, SBP; diastolic,
      DBP; or pulse pressure, PP) is primarily involved. We sought to determine the
      relationship between BP components and parameters of nerve function in type 2
      diabetes. DESIGN: Cross-sectional study. SETTING: Academic medical centre.
      SUBJECTS: A total of 55 consecutive ambulatory patients with type 2 diabetes (age
      62.6 +/-8.0 years, mean +/- SD). INTERVENTIONS: Measurement of clinic BP and 10
      neurophysiological parameters: motor nerve conduction velocity (NCV; median,
      ulnar, posterior tibial and peroneal nerve), sensory amplitude (AMP) and latency
      (LAT; median, ulnar and sural nerve). RESULTS: Univariate analysis showed that
      age, diabetes duration, SBP and PP were negatively correlated with nerve
      function. Regression analysis showed that, after correcting for age, duration of
      diabetes, glycated haemoglobin, body mass index, microalbuminuria and SBP, PP was
      independently and negatively associated with NCV (median, P =0.011; ulnar, P =
      0.001; peroneal, P = 0.006 and posterior tibial, P = 0.005) and signal AMP
      (ulnar, P = 0.027; sural, P = 0.055), and positively associated with signal LAT
      (median, P = 0.083; sural, P = 0.021). SBP was negatively associated with signal
      AMP (median, P = 0.012) and positively associated with LAT (ulnar, P = 0.018). By
      contrast, DBP failed to show any significant correlation with nerve function.
      CONCLUSIONS: The PP is strongly associated with neurophysiological parameters of
      nerve function in patients with type 2 diabetes. This relationship is independent
      of traditional risk factors and other BP components.

PMID- 15953132
TI  - The cost of medical care for patients with diabetes, hypertension and both
      conditions: does alcohol use play a role?
AB  - OBJECTIVE: To estimate and compare the medical costs of individuals with diabetes
      and/or hypertension relative to a matched sample of individuals with neither
      condition, and determine if these costs are significantly influenced by alcohol
      use. RESEARCH DESIGN AND METHODS: Data were obtained from a sample of 799
      patients from eight primary care clinics in south-central Wisconsin between 2001
      and 2002. Medical care costs were calculated within four categories [hospital and
      emergency room (ER) costs, clinic costs, medication costs and total cost] for
      three chronic disease samples [diabetes only (n = 89), hypertension only (n =
      299), and both diabetes and hypertension (n = 209)] as well as a matched sample
      with neither diabetes nor hypertension (n = 202). Annual medical care costs were
      estimated using a combination of insurance billing records, self-reported
      information and chart review. All cost data pertain to a 12-month period in 2001
      2002. In addition to a descriptive analysis of costs across medical service
      categories and samples, we also conducted multivariate analyses of total cost,
      controlling for patient demographics, education, employment, smoking, and
      comorbidities, such as heart disease, hyperlipidaemia, liver disease, chronic
      back pain, asthma, depression, anxiety and bronchitis. RESULTS: The estimated
      differential in total annual medical cost (relative to the control group) was USD
      2183 for diabetes only, USD 724 for hypertension only and USD 3402 for diabetes
      and hypertension. Alcohol use did not significantly impact medical care costs
      amongst individuals with diabetes and/or hypertension. CONCLUSIONS: These cost
      estimates can serve as an important and useful reference source for doctors,
      insurance companies, health maintenance organizations (HMOs) and policy makers as
      they try to anticipate the future medical care needs and associated costs for
      diabetic and hypertensive patients.

PMID- 15953133
TI  - Long-term outcome of a large series of patients surgically treated for
      pheochromocytoma.
AB  - OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a
      consecutive series of surgically treated patients with pheochromocytoma (PC), or
      paraganglioma (PG), from the western region of Sweden between 1950 and 1997.
      PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG
      over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding
      presenting symptoms, tumour characteristics, clinical management and long-term
      outcome after treatment. SETTING: One referral centre for all patients from the
      western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42
      patients died vs. 23.6 expected in the general population (P < 0.001). There was
      no intra- or post-operative mortality. Four patients with sporadic disease died
      of malignant PC and six with hereditary disease of associated neuroectodermal
      tumours. Five patients died of other malignancies, 20 of cardiovascular disease
      and seven of other causes. Besides older age at primary surgery, elevated urinary
      excretion of methoxy-catecholamines was the only observed risk factor for death
      (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after
      surgery more than half were still hypertensive. However, pre- and post-operative
      hypertension did not influence the risk for death versus controls. CONCLUSION:
      Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG
      was unusual, but the patients as a group had an increased risk of death. We
      recommend life-long follow-up of patients treated for PC/PG with screening for
      recurrent tumour in sporadic cases and for associated tumours in hereditary
      cases. This strategy would also be helpful in diagnosing cardiovascular disease
      at an early stage.

PMID- 15953134
TI  - Impact of parathyroidectomy on neutrophil cytosolic calcium in chronic kidney
      disease patients: a prospective parallel group trial.
AB  - OBJECTIVES: Polymorphonuclear leucocytes (PMNs) of chronic kidney disease (CKD)
      patients display elevated basal cytosolic calcium concentrations (iCa(2+)). As
      parathyroid hormone is considered to substantially contribute to the
      inappropriate cellular entry of calcium in uraemia, we hypothesized that
      parathyroidectomy lowers PMN iCa(2+). DESIGN AND SETTING: Prospective parallel
      group trial at a tertiary care centre. SUBJECTS, INTERVENTION AND MAIN OUTCOME
      MEASURES: Two patient cohorts (cohort 1: 14 CKD patients; cohort 2: 14 renal
      transplant recipients) underwent parathyroidectomy for uncontrolled secondary
      hyperparathyroidism. We assessed PMN iCa(2+) (primary objective)
      spectrofluorimetrically 1 day before and 20 days after intervention (secondary
      objective: PMN glucose uptake). Data were compared with those of 16 matched
      maintenance haemodialysis patients (cohort 3), and to 15 healthy subjects (cohort
      4), by generalized estimating equations. RESULTS: PMN iCa(2+) of cohort 1
      decreased over time and was significantly higher than that of cohort 3 before but
      not after parathyroidectomy [mean difference before/after parathyroidectomy: 19.1
      nmol L(-1) (95% confidence interval: 9.4-22.4), P =0.0003/-3.2 (-20.9-14.5), P =
      0.71]. PMN iCa(2+) of cohort 2 decreased over time, but we found no significant
      difference in comparison with cohort 3 [mean difference before/after
      parathyroidectomy: 6.5 nmol L(-1) (-9.4-22.4), P = 0.4/-15.8 (-43.6-12.0), P =
      0.25]. PMN iCa(2+) of all CKD patients was substantially higher in comparison
      with that of healthy subjects [cohort 4 vs. 3: -35.3 (-48.9-21.6), P < 0.001].
      PMN glucose uptake increased significantly in both interventional cohorts in
      comparison with cohort 3. CONCLUSIONS: Parathyroidectomy lowers, but does not
      normalize PMN iCa(2+) of CKD patients. Further variables, possibly uraemic
      retention solutes, control both PMN iCa(2+) and functional responses.

PMID- 15953135
TI  - The use of B-type natriuretic peptide in the management of elderly patients with
      acute dyspnoea.
AB  - OBJECTIVES: The aim of this study was to define the impact of B-type natriuretic
      peptide (BNP) levels on the management of elderly patients presenting with acute
      dyspnoea. DESIGN: We performed a prospective randomized controlled study in 269
      elderly patients at least 70 years of age included in the B-type natriuretic
      peptide for Acute Shortness of breath Evaluation (BASEL) study. Patients were
      randomly assigned to a diagnostic strategy with (n = 136, BNP group) or without
      (n = 133, control group) the use of BNP levels provided by a rapid bedside assay.
      The time to discharge and the total cost of treatment were the primary end
      points. RESULTS: Amongst elderly patients, baseline characteristics were well
      matched between both groups. The use of BNP levels significantly reduced the time
      to discharge (median 9.0 in the BNP group versus 11.0 days in the control group;
      P = 0.029). Total treatment cost was $5381 (95% CI, 4482-6280) in the BNP group
      when compared with $7411 (95% CI, 6180-8642; P = 0.009) in the control group. In
      addition, a significant reduction in 30-day mortality was observed (9% in the BNP
      group versus 17% in the control group; P = 0.039). CONCLUSIONS: Used in
      conjunction with other clinical information, rapid measurement of BNP in the
      emergency department improved the management of elderly patients presenting with
      acute dyspnoea and thereby reduced the time to discharge and the total treatment
      cost. In addition, BNP testing seemed to reduce 30-day mortality.

PMID- 15953136
TI  - Surviving extreme hypercalcaemia--a case report and review of the literature.
AB  - We report a case of extreme hypercalcaemia associated with a parathyroid adenoma
      in a young man. The patient presented with classical symptoms of a hypercalcaemic
      syndrome, and serum calcium and parathyroid hormone levels were 6.92 mmol L(-1)
      and 70.2 pmol L(-1) respectively. After stabilizing the patient and reducing the
      calcium level, a parathyroidectomy was performed. The postoperative course was
      uneventful with rapidly resolving clinical symptoms. Hypercalcaemic crisis is a
      rare but life-threatening complication of primary hyperparathyroidism. It should
      be suspected in acutely ill patients complaining of muscular weakness,
      gastrointestinal and cerebral symptoms. To reduce mortality, it is essential to
      correctly diagnose the condition without delay and provide appropriate emergency
      management correcting hypercalcaemia and dehydration. Successful
      parathyroidectomy quickly relieves symptoms and prevents recurrence.

PMID- 15953137
TI  - Incidence of chronic Philadelphia chromosome negative (Ph-) myeloproliferative
      disorders in the Cote d'Or area, France, during 1980-99.

PMID- 15953139
TI  - Neonatal skin barrier: structure, function, and disorders.
AB  - The development of the human skin from intrauterine to extrauterine life is a
      balletic interplay of maturing layers and interlocking structures. We discuss
      this transition and then branch out to touch on issues of premature infant as
      well as neonatal skin care. Disruption of the barrier function due to toxins and
      development errors are expounded upon. Staph scalded skin syndrome, collodion
      membrane, bullous congenital ichthyosiform erythroderma, autosomal recessive
      ichthyosis (lamellar and congenital ichthyosiform erythroderma), and harlequin
      fetus are used as examples of these disruptions. Discussion of therapy with the
      authors' experience highlights each disease.

PMID- 15953140
TI  - Lumps and bumps in neonates and infants.
AB  - There are many developmental abnormalities that may appear in the neonate and in
      infants when critical steps in embryogenesis fail. These steps are often not
      fatal but can lead to significant morbidity for those patients affected. A
      logical approach is needed in addressing both the diagnostic and therapeutic
      issues that arise when caring for these patients, as various lesions will warrant
      an observational approach, and others may require imaging studies or definitive
      surgical intervention. Additionally, there are other "lumps and bumps" that are
      seen in the neonatal and infantile age groups that include malignancies and
      cutaneous neoplasms with associated systemic sequelae.

PMID- 15953141
TI  - Approach to procedures in neonates.
AB  - Physical constraints and metabolic differences in neonates require that special
      attention is given to performing procedures in this patient group. Neonates have
      a thinner dermis and a greater surface-to-weight ratio, allowing for easier
      invasion through the skin barrier. The enzymes for metabolism of agents and
      defense against organisms inside the body are not fully developed in infants.
      Very premature neonates also have less circulating albumin, making the effective
      concentration of circulating agent even greater. The infant is prone to
      unanticipated movement during procedures, such as rolling on the procedure table.
      The neonatal period is the most common time period for malformations to become
      manifest on the skin, and invasion of some of these lesions can produce
      morbidity. These and other factors affect the choice of the type of procedure
      used, the timing for intervention, and the approach to intervention in this age
      group. This article reviews the important considerations for approaching
      procedures and offers suggestions for safe and effective methods of reliably
      producing the intended outcome.

PMID- 15953142
TI  - Diaper dermatitis that does not quit.
AB  - Diaper dermatitis is one of the most common skin disorders in infants. The humid,
      moist environment under the diaper makes the skin more susceptible to injury from
      exposure to irritants particularly related to urine and feces. A gentle cleansing
      routine, frequent diaper changes, and a thick barrier cream help control this
      condition. Irritant diaper dermatitis should be distinguished from other skin
      conditions that may develop in this sensitive area.

PMID- 15953143
TI  - Congenital melanocytic nevi needing treatment.
AB  - Patients presenting with congenital melanocytic nevi (CMN) need individualized
      treatment based upon nevus size, thickness, location, risk for developing
      melanoma, and psychological characteristics of the patient and family. The
      present authors review CMN types and prognoses, as well as absolute and relative
      indications for treatment. Risks and benefits of several treatment options are
      discussed, including surgical options, such as excision, chemical peels,
      dermabrasion and curettage, and laser therapy. The main focus of treatment is, in
      all cases, to address the concern for developing melanoma, at the same time
      optimizing the aesthetic and functional outcomes.

PMID- 15953144
TI  - Treatment of hemangiomas of infancy.
AB  - Hemangiomas of infancy are the most common tumors of childhood. They are
      clinically heterogeneous and as such require individualized treatment plans.
      Although there are no Food and Drug Administration (FDA)-approved agents for
      treatment of hemangiomas of infancy, there are many widely used therapeutic
      options available. This review highlights the treatments currently in use and the
      factors that direct treatment.

PMID- 15953145
TI  - Hypersensitivity reactions in neonates and infants.
AB  - Although rare, several hypersensitivity reactions can occur in the infant
      population. Several types of hypersensitivity reactions are discussed, including
      urticaria, drug eruptions, erythema multiforme, allergic contact dermatitis, and
      vasculitis (acute hemorrhagic edema of infancy); neonatal lupus also is
      discussed. Although most of these conditions are benign, their presentations can
      be dramatic and a cause of concern for both parents and physicians. Important
      considerations and differences in the diagnosis and management of these
      conditions in children under the age of 6 months are discussed.

PMID- 15953146
TI  - Cutaneous signs of neonatal and infantile immunodeficiency.
AB  - Immunodeficiencies frequently present in the skin antepartum and in the first
      year of life. Although genetic immunodeficiencies are uncommon, the worldwide
      incidence of the acquired immunodeficiency human immunodeficiency virus (HIV) is
      growing. Early diagnosis and treatment of neonatal immunodeficiencies and
      associated infections result in improved quality of life and longer life
      expectancy for these patients. In developed countries, improvements in therapy of
      HIV during pregnancy have resulted in reduced transmission to the neonate. This
      article reviews the common presentations and therapy of genetic and acquired
      neonatal immunodeficiencies.

PMID- 15953147
TI  - Therapeutic approach to selected neonatal eruptions.
AB  - Management of numerous neonatal eruptions has been modified over the past 10
      years. In this article, traditional and developing therapeutic insights are
      applied to both common and uncommon neonatal conditions.

PMID- 15953175
TI  - Festschrift in honour of Ivan Lefkovits.

PMID- 15953178
TI  - Pittsburgh 1962/63 revisited: too many antibodies, too few ribosomes?
AB  - Jerne's success in developing the plaque-forming cell methodology for determining
      the number of specific antibody-producing lymphocytes during the immune response
      has prompted scientists to calculate the number of antibody molecules produced by
      a single cell. In this article, calculations of the rate of antibody production
      are made, and a special attention is called to the number of ribosomes in a cell,
      the rate of protein chain elongation and various other parameters. The generally
      accepted notion of 2000 IgM molecules or some 15,000 IgG molecules per second
      (per cell) remains an acceptable estimate. The article describes the work of Ivan
      Lefkovits and the interaction among research groups leading to quantitative
      evaluations of the components of the immune system.

PMID- 15953179
TI  - Origin and development of a scientific collaboration and a long-lasting
      friendship.
AB  - The aim of this contribution is twofold: to honour Ivan Lefkovits with a short
      recollection of our scientific collaboration in the years 1972-1985 and a summary
      of our joint contribution to studies of the mechanisms and functions of the
      immune system and to acknowledge our long-lasting friendship. Ivan's limiting
      dilution microculture method was adapted to rabbit peripheral blood lymphocytes
      (PBL). The antibody produced in the responding cultures was shown to be
      electrophoretically homogeneous and, in rabbits heterozygous at the b locus, to
      express either one or the other allele. Thus, the antibody released in single
      microcultures was indeed the product of single B-cell clones and allelic
      exclusion, once achieved, was maintained throughout clonal proliferation. In the
      response to streptococcal polysaccharides, analysis of the clonotypes triggered
      in vitro provided information on mechanisms of clonal dominance. A two-stage
      culture system was established, where rabbit PBL were precultured at low cell
      density with antigen before being partitioned in limiting dilution cultures. This
      method provided a new tool for studies of various cellular aspects of the immune
      response. Moreover, it allowed the application of the limiting dilution analysis
      to PBL from unprimed animals. Later, the method was extended with success to
      human PBL, leading to studies of regulatory aspects of immunity in this species.

PMID- 15953180
TI  - Contact between good friends: what limiting dilution analysis taught us.
AB  - The demonstration in the 1960s that T cells collaborated with B cells in enabling
      antibody responses to simple protein antigens opened up the challenge of how to
      investigate the interactions of two rare antigen-specific lymphocytes within a
      vast population. One idea was that T cells made soluble factors that could
      activate B cells at a distance; the other was that rare T cells and B cells came
      into contact. Using limiting dilution analysis, we asked the question 'How many B
      cells could a single T cell collaborate with in the short term?' Unequivocally,
      the answer was just one. This implied a need for cell contact, and coupled with
      the observation for genetic restriction in T-cell/B-cell co-operation, seemed to
      make a watertight case for direct coupling. Claims of diffusible antigen-specific
      factors undermined the importance of our findings at that time. Remarkably, those
      claims have not yet been retracted and our original findings that collaborating T
      cells and B cells must come into contact have never achieved the recognition that
      they deserved.

PMID- 15953181
TI  - From Poisson distribution to interleukins.
AB  - Abstract In the mid-1970s, Ivan Lefkovits and co-workers introduced limiting
      dilution analysis of T and B cells as a method to quantify antigen-specific T and
      B cells. In this study, I describe how my co-operation with Ivan on the subject
      led not only to heated discussions on the validity of the approach but also to
      the identification of interleukin-2 as T-cell-derived factor, capable of
      replacing T-cell help required for the activation of B cells.

PMID- 15953182
TI  - Importance of counting in biology.
AB  - In this study, analysis of biological problems through structural and
      quantitative approaches is described. Classical genetics on major
      histocompatibility complex in avian species has been evaluated. Experiments
      showing that antibodies from various individuals were generally distinct have led
      to further analysis of immunoglobulin light chain diversity by means of
      O'Farrell's 2D gel technique. The transition of the research towards vaccine
      development has been described. 'It's not the voting that's democracy, it's the
      counting.' - Tom Stoppard (Czech-born dramatist), Jumpers (1972) act 1.

PMID- 15953183
TI  - Meeting the demand for innate and adaptive immunities during evolution.
AB  - An ideal immune system should provide each individual with rapid and efficient
      responses, a diverse repertoire of recognition and effector molecules and a
      certain flexibility to match the changing internal and external environment. It
      should be economic in cells and genes. Specific memory would be useful. It should
      not be autoreactive. These requirements, a mixture of innate and adaptive
      immunity features, are modulated in function of the dominant mode of selection
      for each species of metazoa during evolution (K or r). From sponges to man, a
      great diversity of receptors and effector mechanisms, some of them shared with
      plants, are articulated around conserved signalling cascades. Multiple attempts
      at combining innate and adaptive immunity somatic features can be observed as new
      somatic mechanisms provide individualized repertoires of receptors throughout
      metazoa, in agnathans, prochordates, echinoderms and mollusks. The adaptive
      immunity of vertebrates with lymphocytes and their specific receptors of the
      immunoglobulin superfamily, the major histocompatibility complex, developed from
      innate immunity evolutionary lines that can be traced back in earlier
      deuterostomes.

PMID- 15953184
TI  - Peptide-based instruction of suppressor commitment in naive T cells and dynamics
      of immunosuppression in vivo.
AB  - Recent years have witnessed the revival of suppressor T cells that control
      immunity by interfering with the generation of effector T-cell function in vivo.
      The discovery that CD4 T cells with the CD25 surface marker were enriched in
      suppressor activity enabled further phenotypic and functional analysis of the so
      called natural suppressor cells. In vitro characterization showed that these
      cells were anergic, i.e. did not respond to antigenic stimulation with
      proliferation and, instead they suppressed other cells through direct cell
      contact resulting in inhibition of interleukin-2 gene transcription. We have
      analysed the generation and function of suppressor T cells in T-cell receptor
      (TCR) transgenic mice. The results showed that such cells can be generated
      intrathymically when agonist TCR ligands are expressed on thymic epithelial
      cells. Thus generated cells constitute a lineage of cells committed to
      suppression only with the ability to survive for prolonged periods of time in the
      absence of the inducing ligand. Because of appropriate homing receptors such
      cells can accumulate and proliferate in antigen draining lymphnodes after
      antigenic stimulation and suppress proliferation and cytokine secretion of CD4
      and CD8 T cells as well as CD8 T-cell-mediated cytotoxicity. We also attempted to
      generate such cells from naive T cells in secondary lymphoid tissue under
      conditions where expansion of already preformed suppressor T cells could be
      excluded. The results showed that subimmunogenic peptide delivery by osmotic
      minipumps or by peptide containing DEC 205 antibodies yielded CD25+ suppressor
      cells that were phenotypically and functionally indistinguishable from
      intrathymically generated suppressor cells. The experiments with DEC205
      antibodies revealed (i) dose-dependent proliferation of naive T cells and (ii)
      conversion into suppressor T cells of only those T cells that underwent a limited
      number of cell divisions. These results are compatible with other studies that
      were, however, less rigorous in excluding expansion of existing cells as opposed
      to de novo generation of suppressor cells from naive T cells. The fact that
      natural suppressor cells have an essential role in preventing autoimmunity and
      that they can be specifically induced by TCR agonist ligands opens new
      perspectives in preventing autoimmunity, transplant rejection and allergy.

PMID- 15953185
TI  - IgM accelerates affinity maturation.
AB  - Secreted IgM is a potent adjuvant that concentrates antigen into secondary
      lymphoid organs and initiates antibody responses, germinal centre formation and
      is crucial in resolving infections. The current studies investigated the
      influence of specific IgM on both the quantity and quality of antibody produced
      in response to T-dependent and T-independent antigens. The addition of IgM to
      either antigen had no significant effect on the titre or duration of antibody
      responses. However, the presence of specific IgM led to accelerated affinity
      maturation when mice were challenged with low doses of IgM-containing immune
      complexes (IgM-IC) of T-dependent antigens compared with antigen alone.
      Interestingly, the administration of higher concentrations of IgM-IC increased
      follicular deposition of antigen but did not result in accelerated affinity
      maturation or in higher antibody affinities. The administration of IgM complexed
      with T-independent antigens had no effect on antibody titre, duration or affinity
      maturation, despite increased antigen deposition in lymphoid follicles. Together,
      these results demonstrate that IgM accelerates affinity maturation in immune
      responses to T-dependent antigens and implies an antigen optimum exists for the
      generation of high affinity antibodies. The data also suggest IgM plays an
      important role in the induction of CD4 T cells, facilitating germinal centre
      formation and function.

PMID- 15953186
TI  - Dissection of systems, cell populations and molecules.
AB  - This paper summarizes studies on antibody formation in the bone marrow and the
      suppressive effects of intravenous immunization with allogeneic blood cells on T
      cell function in mice. The latter studies were extended by employing the limiting
      dilution culture system developed in Ivan Lefkovits' laboratory and implemented
      in collaboration with Lucien Aarden. Thereby, the functional data were
      complemented with frequencies of alloantigen-activated helper (Th) and suppressor
      T cells after intravenous alloimmunization. These results led the Rotterdam group
      to studies on the prevention of rejection of the foetal 'allograft'. Th cells are
      central in foetal allograft rejection and pregnancy success. Characteristic for
      human pregnancy is the production of the glycoprotein chorionic gonadotropin
      (hCG) hormone. The in vivo liberated peptide fragments originating from nicking
      of the sequence MTRVLQGVLPALPQ in the beta-chain of hCG were considered for their
      immunoregulating capacity related to pregnancy success. These peptides - prepared
      synthetically - (MTR, MTRV, LQG, LQGV, VLPALP and others) indeed showed a
      remarkable spectrum of biological effects (e.g. modulation of angiogenesis,
      inhibition of septic shock syndrome, prevention of diabetes and reduction of
      ischaemia-reperfusion damage). The paper interprets and generalizes these
      findings and projects them into various research directions, especially towards
      the proteomics framework studies built up in Ivan Lefkovits' laboratory in the
      nineties. During the time period, when Ivan spent a mini-sabbatical in Rotterdam
      (months after closing down the BII) more detailed discussions were intiated. This
      paper is meant to keep the discussions between the involved research groups going
      on.

PMID- 15953187
TI  - Stromal cells attract B-cell progenitors to promote B-cell-B-cell contact and
      maturation.
AB  - The in vitro differentiation of B-lineage progenitors into Ig-secreting mature B
      cells has classically required a co-culture system containing lipopolysaccharide
      (LPS) and stromal cells. We have previously showed that B-lineage progenitors
      cultured in round-bottomed wells can mature and secrete immunoglobulin M (IgM) on
      par with cultures containing stromal cells. This clearly demonstrates that any
      factors essential for progenitor cell maturation can be found in cultures
      containing media, serum, LPS and B-cell progenitors. However, stromal cells are
      important for the maturation observed when cells are cultured in flat-bottomed
      wells. We hypothesized that stromal cells may attract B-cell progenitors and
      promote contacts between responsive cells, a phenomenon that is mimicked by the
      cultures in round-bottomed wells. In this study, we explore how stromal cells
      accomplish these functions. We show that stromal cells attract B-cell progenitors
      in a pertussis toxin-sensitive manner. The stromal cell line S17 produces the
      chemokine CXCL12, which is able to induce the chemotaxis of B-lineage
      progenitors. Chemotaxis can be blocked by a small peptide inhibitor (T134) of
      CXCR4, the CXCL12 receptor. Further, disrupting chemotaxis can reduce the
      supportive role played by S17 when B-lineage progenitors are cultured in flat
      bottomed wells.

PMID- 15953188
TI  - Respiratory vaccination of mice against influenza virus: dissection of T- and B
      cell priming functions.
AB  - We find that a single respiratory administration of replicationally inactivated
      influenza A viral particles most often elicits a waning serum antibody response,
      as the long-sustained bone marrow antiviral plasma cell populations
      characteristically induced by viral infection are lacking, though antiviral
      plasma cells at other sites may occasionally persist for a long time. To
      determine whether this alteration in the pattern of the B-cell response is a
      reflection of the nature of T-helper (Th) priming, we simultaneously primed B
      cells with inactivated influenza A/PR8(H1N1) and Th cells with infectious
      A/x31(H3N2). We show that Th cells cross-react extensively between these two
      viruses, although the antibody response to viral envelope glycoproteins is
      completely non-cross-reactive. Th cells primed by infectious A/x31 have little
      impact on the antibody response specifically elicted from naive B cells by
      inactivated A/PR8 viruses, suggesting that the characteristic vigour of the
      antibody response to influenza viral infection depends on the direct interaction
      of antiviral B cells with virally infected dendritic cells. Memory B cells primed
      by inactivated influenza viral particles however, respond rapidly to secondary
      challenge with live or inactivated viruses, promptly populating bone marrow with
      antiviral plasma cells. Moreover, Th cells primed by previous live A/x31 viral
      challenge alter the pattern of the response of naive B cells to live A/PR8
      challenge by accelerating the appearance of anti-H1/N1 plasma cells in bone
      marrow, eliminating the early spike of anti-H1/N1 plasma cells in the mediastinal
      node, and generally diminishing the magnitude of the lymph node response.
      Inactivated A/PR8 and infectious A/x31 are both effective vaccines against A/PR8
      infection, as mice preimmunized with either vaccine exhibit much more rapid viral
      clearance from the lung after infectious A/PR8 challenge. In fact, even when
      given during a course of anti-CD8 treatment to preempt cross-reactive cytotoxic T
      cells, live A/x31 is a more effective vaccine against A/PR8 infection than is
      inactivated A/PR8 itself.

PMID- 15953189
TI  - Mobile classification in microarray experiments.
AB  - In a homogeneous group of samples, there are genes whose expression variations
      can be attributed to factors other than experimental errors. These factors can
      include natural biological oscillations or metabolic processes. These genes are
      rarely classified as 'interesting' based on their variability profile. However,
      their dynamic behaviour can tease out important clues about naturally occurring
      biological processes in the organism under study and can be used for group
      classification. Dynamical discriminate function analysis was developed on the
      concept that stable classification parameters (roots) can be derived from highly
      variable gene-expression data. Stability of these combinations implies a strongly
      compensatory relationship that may divulge functional interconnections.

PMID- 15953190
TI  - Immunoadsorbent assay application for studies of protein mixtures and usage of
      paper carriers.
AB  - Proteins immobilized on insoluble carriers or immunoadsorbents are now widely
      used in many areas of biological research. They are especially efficient in
      studies of complex protein mixtures because immunoadsorbents are very useful for
      isolation of individual components for further investigation. Antibodies
      immobilized on paper retain their specific activity and can be applied as very
      sensitive measurement tool.

PMID- 15953191
TI  - Mouse hepatitis virus 3 binding to macrophages correlates with resistance to
      experimental infection.
AB  - Mouse hepatitis virus 3 (MHV3) infection of A/J and BALB/c mice has been used as
      a model of resistance/susceptibility. A/J mice recover from a mild disease after
      4-6 days of infection and the BALB/c mice develop an acute hepatitis and die
      after 3-4 days of infection. In view of studying the MHV3 binding to cells or
      cell extracts, we performed an enzyme-linked immunosorbent assay-like virus
      binding assay, preparing microplates with L929 cells, A/J or BALB/c mouse
      macrophages and also with proteins extracted from these cells. Higher MHV3
      bindings were observed to proteins of BALB/c macrophages than to the A/J ones.
      The interferon-gamma (IFN-gamma) activation led to a reduction of MHV3 binding
      only to proteins of resistant A/J mouse macrophages. Our experiments contribute
      to the hypothesis that IFN-gamma activation of macrophages plays an important
      role against MHV3 infection by downregulating the expression of viral receptors.

PMID- 15953192
TI  - Induction of systemic antitumour resistance with targeted polymers.
AB  - Conjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) represent a new
      generation of antibody-targeted polymeric anticancer drugs with both cytotoxic
      and immunoprotecting/immunomobilizing activity. 20-90% of mice that are cured of
      EL4 mouse T-cell lymphoma, BCL1 mouse B-cell leukaemia and 38C13 mouse B-cell
      lymphoma by injection of doxorubicin-HPMA conjugate develop a long-lasting memory
      and systemic antitumour resistance. It is suggested that the main activity of the
      polymeric drug, directly after application is - due to the high level of the drug
      - of cytotoxic and cytostatic nature. Thereafter, long-term conjugates persist at
      low concentration in the circulation, which are capable of mobilizing the defence
      mechanisms of the host. Until now, seven patients with generalized carcinoma were
      treated with doxorubicin-HPMA-human-Ig conjugate. Disease stabilization, lasting
      from 6 to more than 18 months, was recorded.

PMID- 15953193
TI  - Interaction of mucosal microbiota with the innate immune system.
AB  - Organisms live in continuos interaction with their environment; this interaction
      is of vital importance but at the same time can be life threatening. The largest
      and most important interface between the organism and its environment is
      represented by surfaces covered with epithelial cells. Of these surfaces, mucosae
      comprise in humans approximately 300 m2, and the skin covers approximately 1.8 m2
      surface of the human body. Mucosal tissues contain two effector arms of the
      immune system, innate and adaptive, which operate in synergy. Interaction with
      commensal bacteria, which outnumber the nucleated cells of our body, occurs
      physiologically on epithelial surfaces; this interaction could pose the risk of
      inflammation. The mucosal immune system has developed a complex network of
      regulatory signalling cascades that is a prerequisite for proper activation but
      also for a timely inactivation of the pathway. As demonstrated in gnotobiotic
      animal models of human diseases, impaired regulation of mucosal responses to
      commensal bacteria plays an important role in the development of several
      inflammatory and autoimmune diseases.

PMID- 15953194
TI  - Coding joint diversity in mature and immature B-cell lines.
AB  - Antigen receptor gene rearrangement is regulated by many factors in B and T
      lymphocytes. The sequences of the gene segments themselves, their associated
      recombination signal sequences (RSS), expression of the RAG genes and the
      chromatin accessibility of the particular gene segments to be rearranged all
      influence the outcome of recombination and thus antigen receptor diversity. In
      the present study, we have evaluated the effect of variations in RAG activity
      level on the junctional diversity of coding joint sequences. Using the pre-B-like
      204-1-8 and the mature B DR3 cell lines under different transfection conditions,
      we were able to investigate recombination activity levels that varied 100-fold.
      We evaluated the sequences of the coding joints for junctional diversity
      resulting from nucleotide addition or deletion. Surprisingly, we found that the
      sequence of coding joints of these recombinants did not exhibit significant
      variation despite the large difference in recombination frequency. Our results
      indicate that the fidelity of the joining phase of V(D)J recombination is not
      jeopardized by varying RAG activity.

PMID- 15953195
TI  - From clones of cells to cloned genes and the proteinpaedia.
AB  - This brief description follows the association of the author with Ivan Lefkovits
      from 1971 until this volume. Sketches of our mutual interests are included. Time
      periods in California, Basel and Texas are described. Decisions about preparing
      new tools for clonal analysis are elucidated, and experimental approaches leading
      to the x-omic revolution are described.

PMID- 15953196
TI  - Genomics and systems biology--how relevant are the developments to veterinary
      pharmacology, toxicology and therapeutics?
AB  - This review discusses some of the recent developments in genomics and its current
      and future relevance for veterinary pharmacology and toxicology. With the rapid
      progress made in this field several new approaches in pharmacological and
      toxicological research have developed and drug discovery and drug development
      strategies have changed dramatically. In this review, the term genomics is used
      to encompass the three sub-disciplines transcriptomics, proteomics and
      metabolomics (or metabonomics) to describe the formation and fate of mRNA,
      proteins and metabolites, respectively. The current status and methods of the
      technology and some applications are briefly described. Although the DNA
      sequencing programmes are receiving considerable attention, the real value of
      genomics for pharmacology and toxicology is brought by the parallel developments
      in bio-informatics, bio-statistics and the integration of biology with
      mathematics and information technology. The ultimate level of integration is now
      mostly called systems biology, where mRNA, proteins and metabolites are being
      analysed in parallel, using a complete arsenal of analytical techniques (DNA
      array, LC-MS/MS, GC-MS/MS, NMR, etc.). The information thus collected is
      analysed, integrated, linked to database information and translated to pathways
      and systems. This approach offers an enormous potential to study disease
      mechanisms and find new drug targets. Thus far, genomics and systems biology have
      not been introduced significantly in typical veterinary pharmacological and
      toxicological research programmes. The high costs and complexity connected to
      these large projects often form major obstacles for research groups with limited
      budgets. In other veterinary areas and disciplines, including infectious
      diseases, animal production and food-safety more examples of application are
      available. Genomics and bio-informatics provide outstanding opportunities to
      study pharmacology and toxicology in a more holistic way, taking into account the
      complexity of biological systems and based on the basic principles of physiology
      and the concept of homeostasis. Knowledge of biology, in vivo and in vitro
      models, and comparative pharmacology/toxicology is essential here, creating
      excellent opportunities for the veterinary trained scientist.

PMID- 15953197
TI  - Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue
      chambers in beef calves after subcutaneous administration of ceftiofur
      crystalline free acid sterile suspension in the ear pinna.
AB  - The effect of Mannheimia haemolytica infection on the penetration of ceftiofur
      and desfuroylceftiofur metabolites into tissue chambers was studied in cattle
      after subcutaneous administration of ceftiofur crystalline free acid sterile
      suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each
      of 12 calves. Approximately 45 days after implantation, two chambers were
      inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the
      remaining two chambers were inoculated with sterile phosphate-buffered saline.
      Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in
      the middle third of the caudal ear pinna of each calf. Chamber fluid and blood
      samples were collected at predetermined times for 10 days following dosing and
      analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance
      liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur
      metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2
      microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of
      ceftiofur and desfuroylceftiofur metabolites were significantly higher than those
      in non-infected tissue chamber fluid, which correlated with significantly higher
      total protein concentration in infected tissue chambers. These results indicate
      that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected
      to provide effective therapy of susceptible bacterial infections for a period of
      at least 1 week.

PMID- 15953198
TI  - Effects of moxifloxacin on QT interval in conscious dogs.
AB  - Moxifloxacin has been shown to induce QT prolongation in both clinical and
      preclinical models. However, the ability to observe this effect at clinically
      relevant concentration in normal conscious dogs has not been reported. The
      purpose of this study was to investigate the effects of moxifloxacin on the QT
      interval in conscious, healthy dogs. Four male mongrel dogs were chronically
      instrumented for the measurement of arterial blood pressure, left ventricular
      blood pressure, cardiac output, electrocardiograms (ECGs), and body temperature.
      Animals were administered a 1-h i.v. infusion of moxifloxacin once per day via a
      catheter in the cephalic vein. Each dog received all doses (0, 1, 10, 25 and 50
      mg/kg) in an escalating fashion. Moxifloxacin caused a statistically significant
      increase in arterial blood pressure at 50 mg/kg. A dose-response effect on QT and
      QTc prolongation was observed. A statistically significant prolongation in the QT
      interval was observed at 10, 25 and 50 mg/kg and a prolongation of QTc was
      observed at 25 and 50 mg/kg. These effects occurred at clinically relevant plasma
      concentrations. This study demonstrate that a study design with four dogs was
      sensitive enough to measure moxifloxacin-induced QT prolongation at clinically
      relevant plasma concentrations.

PMID- 15953199
TI  - Selamectin is a potent substrate and inhibitor of human and canine P
      glycoprotein.
AB  - The transport of the antiparasitic agents, ivermectin, selamectin and moxidectin
      was studied in human intestinal epithelial cell monolayers (Caco-2) and canine
      peripheral blood lymphocytes (PBL). Both models expressed the mdr1-coded 170 kDa
      ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp). Fluxes of the P-gp
      substrate rhodamine-123 (Rh-123) across Caco-2 monolayers showed that ivermectin
      and selamectin acted as potent P-gp inhibitors with IC50 values of 0.1 microm. In
      contrast, moxidectin was a weaker P-gp inhibitor with an IC50 of 10 microm. The
      transport of radiolabelled ivermectin, selamectin and moxidectin through Caco-2
      monolayers showed that ivermectin, selamectin and moxidectin were P-gp substrates
      with secretory/absorptive ratios of 7.5, 4.7 and 2.6 respectively. Secretory
      transport of [3H]-ivermectin and [3H]-selamectin was blocked by the P-gp
      inhibitor, verapamil. Ivermectin and selamectin inhibited the efflux of Rh-123
      from PBL and the concentration of inhibition was similar to that of verapamil. In
      contrast, moxidectin did not have a significant effect on Rh-123 efflux from PBL.
      The data suggest that ivermectin and selamectin are potent P-gp substrates, while
      moxidectin is a weak one.

PMID- 15953200
TI  - Studies on itraconazole delivery and pharmacokinetics in mallard ducks (Anas
      platyrhynchos).
AB  - Avian aspergillosis is commonly treated with itraconazole (ITZ). This paper
      describes two studies using mallard ducks (Anas platyrhynchos). The first study
      evaluated in vivo release of ITZ from subcutaneously injected controlled-release
      gel formulations and the second study compared pharmacokinetic parameters for two
      ITZ oral suspensions. ITZ-A suspension was prepared by mixing contents of
      commercially available capsules with hydrochloric acid and orange juice. ITZ-B
      suspension was prepared by dispersing the complex of the drug with hydroxypropyl
      beta-cyclodextrin in water. Concentrations of ITZ and its active metabolite,
      hydroxyitraconazole (OH-ITZ), in plasma and tissue samples were measured using
      high-performance liquid chromatography. In the second study, drug concentrations
      in plasma samples were also analyzed using a bioassay. After administration of
      two ITZ controlled-release formulations, plasma and tissue concentrations of ITZ
      and OH-ITZ were either very low (< or = 52 ng/mL) or undetectable. Exceptions
      included skin, subcutaneous fat, and muscle adjacent to the injection site. The
      drug from ITZ-A and ITZ-B suspensions was absorbed after oral administration. ITZ
      pharmacokinetic parameters for both suspensions in mallard ducks were similar and
      the bioassay successfully measured ITZ equivalents in plasma samples from ducks.

PMID- 15953201
TI  - Development and validation of a new model of inflammation in the cat and
      selection of surrogate endpoints for testing anti-inflammatory drugs.
AB  - In laboratory animals many models of inflammation have been developed for
      preclinical evaluation of the pharmacological profiles of nonsteroidal anti
      inflammatory drugs (NSAIDs). In contrast, in species of veterinary interest,
      including the cat, NSAIDs have been studied mainly using dose-titration or dose
      confirmation studies in clinical subjects. This is due to the scarcity of
      appropriate animal models and to the associated lack of quantitative validated
      endpoints describing the magnitude and time course of drug response.
      Determination of pharmacokinetic/pharmacodynamic (PK/PD) relationships provides a
      powerful approach for the selection of effective and safe dosage regimens. In
      this study, a paw inflammation model in the cat was developed for the preclinical
      evaluation of NSAIDs using PK/PD modelling. Subcutaneous injection of 500 mg
      kaolin in the paw produced a well-defined and reproducible inflammatory response
      that lasted 4-5 days. Several endpoints were assessed for their clinical
      relevance and for their metrological performance (accuracy and reproducibility).
      Body temperature, lameness scoring, locomotion tests and possibly skin
      temperature were the most appropriate endpoints for testing the antipyretic,
      analgesic and anti-inflammatory effects of NSAIDs in the cat.

PMID- 15953202
TI  - Effect of dietary fat on oral bioavailability of tepoxalin in dogs.
AB  - A pharmacokinetic study was conducted to compare the oral bioavailability of
      tepoxalin and its pharmacologically active acid metabolite in fasted dogs and
      dogs fed either a low-fat or high-fat commercial diet. Using a cross-over design,
      six beagles were administered tepoxalin (10 mg/kg) intravenously (i.v.) and
      orally (p.o.) after being fed one of three diets (fasted, low-fat, or high-fat).
      Thereafter, blood samples were collected at frequent intervals, concentrations of
      tepoxalin and acid metabolite in plasma were determined by high performance
      liquid chromatography, and pharmacokinetic parameters were estimated. After i.v.
      dosing, the mean (+/-SD) half-life of elimination (t(1/2(beta))) was 2.45 +/-
      1.47 h. After p.o. administration, plasma concentrations of acid metabolite were
      consistently higher than corresponding concentrations of the parent tepoxalin,
      indicating that tepoxalin is subject to a substantial first-pass effect. Mean (+/
      SD) peak concentrations of tepoxalin were significantly higher after feeding of
      low-fat (1.08 +/- 0.37 microg/mL) and high-fat (1.19 +/- 0.29 microg/mL) diets
      than in fasted dogs (0.53 +/- 0.20 microg/mL), suggesting that feeding improves
      oral bioavailability.

PMID- 15953203
TI  - L-Bupivacaine 0.5% vs. racemic 0.5% bupivacaine for caudal epidural analgesia in
      horses.
AB  - Bupivacaine is available as a racemic mixture of its enantiomers, d-bupivacaine
      and l-bupivacaine (LB). The aim of this randomized, double-blind study was to
      investigate the clinical efficacy and safety of S(-)-bupivacaine compared with
      standard racemic bupivacaine (RB) in horses under caudal epidural analgesia. Two
      treatments were administered to each horse, with a 2-week interval between
      subsequent treatments. Treatment 1 consisted of 0.5% LB at a dose of 0.06 mg/kg
      of body weight, and treatment 2 consisted of 0.5% RB at a dose of 0.06 mg/kg of
      body weight. Epidural injections were given in all animals between the first and
      second coccygeal vertebra. Heart rate (HR), arterial pressures, respiratory rate
      (RR), rectal temperature (RT), analgesia, and motor blocking were determined
      before drug administration (basal) and 5, 10, 15 and 30 min after drug
      administration, and at 30 min intervals thereafter. There were no significant
      differences between the two treatments in the quality of sensory and motor block.
      The duration of analgesia was 320 +/- 30 min (mean +/- SD) for RB and 360 +/- 42
      min for LB. HRs and RRs, arterial pressures and RT did not change (P < 0.05)
      significantly from basal values after epidural administration of LB or RB. This
      study supports that 0.5% LB is an effective alternative to RB in caudal epidural
      analgesia in conscious, standing horses. The use of LB vs. RB warrants further
      investigation, particularly for long-lasting surgery in the perineal region.

PMID- 15953205
TI  - The pharmacokinetics of vedaprofen and its enantiomers in dogs after single and
      multiple dosing.
AB  - Vedaprofen is a chiral nonsteroidal anti-inflammatory drug that has been
      developed as a gel formulation for oral administration to dogs and horses. The
      pharmacokinetics of vedaprofen and its enantiomers were studied in beagle dogs
      after single (intravenous solution and oral gel) and multiple (oral gel) dosing
      at a dosage of 0.5 mg/kg body weight. Plasma concentrations of vedaprofen and its
      enantiomers were analysed by HPLC. The plasma protein binding of vedaprofen was
      studied by ultrafiltration. The absorption of vedaprofen was rapid (tmax 0.63 +/-
      0.14 h) and almost complete after oral administration (bioavailability 86 +/-
      7%). The terminal half-lives after intravenous and oral administration, 16.8 +/-
      2.2 and 12.7 +/- 1.7 h respectively, were of the same order of magnitude.
      Enantioselective analysis showed that the R(-) enantiomer predominated in plasma.
      The change in the plasma time course of the plasma R(-)/S(+) enantiomer
      concentration ratio over time was similar after single intravenous and oral
      dosing, with R(-)/S(+) ratios in the AUC of 1.7 +/- 0.5 and 1.9 +/- 0.2
      respectively. Plasma protein binding of vedaprofen and its enantiomers was high
      (> 99.5%). Vedaprofen is absorbed rapidly from the gastrointestinal tract, has a
      high bioavailability and does not accumulate in plasma in dogs following repeated
      oral administration.

PMID- 15953204
TI  - Comparison of topical lidocaine/prilocaine anesthetic cream and local
      infiltration of 2% lidocaine for episioplasty in mares.
AB  - Local anesthesia and tissue inflammation associated with lidocaine infiltration
      and lidocaine/prilocaine topical anesthetic cream for episioplasty in mares were
      compared. Twenty-two mares were randomly assigned to lidocaine or
      lidocaine/prilocaine topical anesthetic cream treatment groups. Perineum and
      vulva were cleaned, 8-12 g (approximately 1 g/cm per side of vulva) of topical
      anesthetic cream was applied, and the area was covered by plastic wrap 30 min
      prior to beginning procedure. Alternately, lidocaine was injected (1 mL) every
      centimeter just prior to the procedure. Episioplasty was conducted using standard
      methods, but employing simple interrupted sutures. Horses were not sedated and
      use of a twitch was recorded. Four millimeter punch biopsies were harvested 1, 3,
      and 10 days following episioplasty and scored for degree of inflammation by a
      blinded pathologist. Clinical inflammation scores were assigned when biopsies
      were obtained. Seven of 11 horses receiving lidocaine infiltration required
      twitching, but none of the horses that received the anesthetic cream required
      twitching. Six of 11 and seven of 11 of the lidocaine and anesthetic cream
      groups, respectively, required twitching for episioplasty. Except for the
      clinical scores on day 3, no statistical differences for clinical and
      histopathologic scores between samples from the two treatment groups for a given
      day were identified. Use of lidocaine/prilocaine topical anesthetic cream was as
      effective as lidocaine infiltration in providing local anesthesia when performing
      episioplasty in mares. Its use decreased the need for twitching horses as well as
      the risk of deformation of the labia caused by lidocaine infiltration.

PMID- 15953206
TI  - Acute cardiovascular effects of tacrolimus in the isolated guinea pig heart.

PMID- 15953207
TI  - Pharmacokinetics of florfenicol in the red pacu (Piaractus brachypomus) after
      single dose intramuscular administration.

PMID- 15953208
TI  - Pharmacokinetics of ethambutol (EMB) in elephants.

PMID- 15953209
TI  - Efficacy of difloxacin against respiratory infections of lambs.

PMID- 15953210
TI  - Exploring clinician uncertainty in the diagnosis and treatment of attention
      deficit hyperactivity disorder.
AB  - Based upon analyses of interview data collected from twenty-six clinician
      respondents, this study explores two facets of clinician uncertainty related to
      the diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) in
      children. First, this study explores clinician reservations about the diagnostic
      validity of ADHD as it is described by the American Psychiatric Association
      (1994) in DSM IV. Second, this study explores clinician ambivalence regarding the
      physical and social-psychological side-effects of stimulant medications, such as
      Ritalin. In applying the sociological discussions that address uncertainty in
      clinical settings and through reviewing a sizable cross-section of the popular
      and research-oriented literature demonstrating the contentious nature of the ADHD
      phenomenon, this study illustrates that clinicians do not practice within a
      vacuum, but are instead largely affected by the marked scepticism that surrounds
      ADHD. In being affected by this scepticism, it is concluded that clinicians who
      assess and treat ADHD are autonomous in how they interpret the diagnostic and
      treatment protocols for this mental disorder.

PMID- 15953211
TI  - Biographical work and returning to employment following a spinal cord injury.
AB  - The question of returning to work after the onset of severe impairment is
      inseparable from the biographical work that disabled people need to achieve.
      Qualitative analysis of interviews I carried out among people who had become
      paraplegic and among rehabilitation professionals offered the following insights:
      * During a period extending beyond rehabilitation, interviewees were absorbed by
      the work of coming to terms with their impairment and delegated the question of
      occupation to the professionals. At a later date, some of them manage to recast
      their biographies and gain ownership of their occupations and activities for
      themselves. An open environment, which offers negotiable opportunities and space
      for relationships to form, encourages the development of biographical work.
      Nowadays, the question of exclusion would appear to dominate the domain of
      rehabilitation. The belief that prolonged inactivity engenders marginalisation
      has led professionals to develop a doctrine whereby they encourage their patients
      to plan for their professional activities from a very early stage. Struggling
      with different time demands (for example, lengthy administrative procedures and
      reduced rehabilitation time) professionals organise their work around a new time
      frame which conflicts with their expertise and is difficult to reconcile with the
      trajectories of disabled people.

PMID- 15953212
TI  - Parenting a young person with mental health problems: temporal disruption and
      reconstruction.
AB  - The article explores the experiences of parents living with a young person with
      mental health problems. Qualitative interviews were conducted with 25 parents (18
      mothers and 7 fathers) whose child had a diagnosed psychiatric condition. It is
      argued that the parents engaged in a form of narrative reconstruction of their
      dual roles as parents and carers as they tried to make sense of the illness in
      their lives by reconstructing their past, present and future experiences. The
      concept 'responsibility' was threaded through the parents' narratives and is
      discussed in relation to three key dimensions - moral responsibility; causal
      responsibility; and responsibility for self. It is argued that the moral
      imperative to care for their child was the dominant theme in the parents'
      narratives but that this was challenged by their lack of knowledge of psychiatric
      conditions; their interactions with healthcare professionals; their relationships
      with their child; and their difficulties in coping with the extended parental
      responsibility that arose from their caring role.

PMID- 15953213
TI  - Living with chronic illness in the family setting.
AB  - This paper discusses the ways in which family practices and family relationships
      interact with the demands of diet-related chronic illness. It uses a study that
      examined the management of food and diet in families where one member had been
      diagnosed with one of two medical conditions: coronary heart disease (CHD) and
      coeliac disease (CD). The data revealed a propensity for family members,
      especially female partners/wives, to see the tasks and activities related to the
      special diet in terms of family practices rather than individual (patients')
      responsibilities. These family practices could be seen to be gendered but also
      part of the ongoing lived experience of the family relationship. It is speculated
      that this is part of a desire for what Giddens has described as 'ontological
      security'. Thus, the special diet tends to be assimilated into family practices
      in ways that promote a sense of continuity that is described as 'normality' or
      'leading a normal life'.

PMID- 15953214
TI  - Researching the disabled identity: contextualising the identity transformations
      which accompany the onset of impairment.
AB  - This paper outlines a recent study which, in an attempt to illuminate the
      processes surrounding the formation of what is increasingly being referred to as
      'the disabled identity', set out to explore the effects of the onset and ongoing
      experience of impairment in relation to disabled people's self-perceptions. A
      grounded theory approach was adopted and the data derived from the stories of 92
      people from four countries, through telephone dialogues and autobiographical
      material which sought to answer, or, in the case of unsolicited material, could
      be said to have answered, the question: How has [the illness or disabling
      condition] affected the ways in which you see yourself and how others treat you?
      The major areas of identity which were found to be affected by disability were
      those which related to independence, work and appearance/sexuality, all of which
      were heavily influenced by the negative attitudes of others and each of which
      were related to qualities which could be argued to represent the pivotal
      characteristics separating the 'affiliated and the marginalised' in contemporary
      Western society.

PMID- 15953216
TI  - The patient with shock: is there any role for the non-invasive monitoring of
      cardiac output?

PMID- 15953217
TI  - What are we waiting for? Understanding, measuring and reducing treatment delays
      for cardiac patients.

PMID- 15953218
TI  - Emergency physicians can reliably assess emergency department patient cardiac
      output using the USCOM continuous wave Doppler cardiac output monitor.
AB  - OBJECTIVES: 1 To develop a training package for ultrasonic cardiac output monitor
      (USCOM) cardiac output assessments and determine the number of proctored studies
      necessary for skill acquisition. 2 To develop criteria for acceptance of cardiac
      output results obtained with the USCOM. 3 To evaluate the reliability of USCOM
      cardiac output assessments in the ED. METHODS: The authors developed an
      audiovisual training package. Four emergency physicians and one geriatrician
      subsequently underwent hands-on training, and skill acquisition was assessed at
      the fifth, 10th, 15th and 20th examinations. Six image-scoring criteria were
      developed to assess acoustic image quality. Upon completion of training a
      protocol was developed to optimize interassessor reliability. Two trained
      emergency physicians then performed blinded examinations on ED patients using the
      protocol and interassessor reliability was evaluated. RESULTS: During training
      average image score improved between the fifth and 20th assessed patient from 4.6
      (95% CI 4.0-5.3) to 5.5 (95% CI 5.0-6.0, Pt-test=0.02) out of 6 and average intra
      assessor cardiac output difference improved from 17% (95% CI 4-25) to 5% (95% CI
      0-11, Pt-test=0.02). Analysis of 52 cardiac output assessments in 21 ED patients
      demonstrated excellent interassessor correlation (r=0.96, 95% CI 0.90-0.98,
      P<0.001). The average interassessor difference in cardiac output and index was
      0.2 L/min (4%, 95% CI 3-6) and 0.1 L/min/m2 (4%, 95% CI 2-6), respectively.
      CONCLUSION: Emergency physicians with no prior ultrasonographic experience can be
      trained to obtain reliable cardiac output estimations upon conscious ED patients
      with the USCOM over the course of 20 patient assessments.

PMID- 15953219
TI  - Pilot study of Myers Briggs Type Indicator personality profiling in emergency
      department senior medical staff.
AB  - OBJECTIVE: To study the viability of using the Myers Briggs Type Indicator (MBTI)
      in senior ED medical staff and to examine what trends, if any, in personality
      types exist within the specialty. METHODS: A pilot cross-sectional survey was
      undertaken during which a standard MBTI questionnaire was sent anonymously to a
      convenience sample of senior ED medical staff in Tasmania and South Australia.
      Completed surveys after a second mailing were analysed and the results collated.
      RESULTS: Of 82 senior ED medical staff surveyed, 68 returned completed
      questionnaires (response rate 83%). The single most common personality group in
      the cohort was the (Extrovert/Intuitive/Thinking/Judging) ENTJ type exhibited by
      12 (17.7%, 95% CI 9.4-28.7%) clinicians in the cohort. This group is present at a
      rate of 3% in the general population. In terms of individual traits, Introversion
      was exhibited by 33 (48.5%, 95% CI 36.2-61%), Intuitive traits by 40 (58.8%, 95%
      CI 46.2-70.6%), Thinking traits by 40 (58.8%, 95% CI 46.2-70.6%) and Judging
      traits by 53 (77.9%, 95% CI 66.2-87.1%) of our cohort of senior ED medical staff.
      CONCLUSION: Our senior ED medical staff cohort suggests notable variations from
      the general population in terms of their MBTI profiles.

PMID- 15953220
TI  - Factors that impact upon the time to hospital presentation following the onset of
      chest pain.
AB  - INTRODUCTION: Although morbidity and mortality associated with chest pain are
      related to time to intervention, many patients have delayed ED presentations. We
      aimed to assess the extent of and reasons for prehospital delay, and identify
      patient subgroups more at risk of delayed presentation. METHODS: This was an
      analytical, cross-sectional survey of patients with undifferentiated, potentially
      ischaemic chest pain, at a tertiary referral ED. Data were collected on the
      circumstances surrounding the chest pain incident (including components of total
      prehospital time) and the proportion of delayed presentations (defined as >3 h).
      Multiple linear regression determined variables significantly associated with
      prehospital time. RESULTS: One hundred and fifty patients were enrolled. Mean age
      was 51.9+/-15.9 years and 90 (60.0%, 95% CI 51.7-67.8) were male. The mean total
      prehospital time was 6.38 h (median 3.17). Seventy-nine (52.7%, 95% CI 44.4-60.8)
      patients had a delayed presentation (>3 h) and those most at risk of this were
      those at home at pain onset and those with a history of AMI. The decision time
      (from onset of pain to decision to present) comprised the majority (82.8%) of
      total prehospital time. Factors positively associated with decision time were:
      waiting to see if symptoms resolved (P<0.0001), seeking GP advice (P<0.0001),
      fluctuating symptoms (P=0.02), embarrassment (P=0.01) and attributing symptoms to
      muscle problems (P=0.04). Nine patients diagnosed with AMI had a mean total
      prehospital time of 10.2 h. CONCLUSION: Intensified efforts are required to
      promote awareness of the need to present directly to the ED upon the onset of
      chest pain. The factors associated with decision delay may help to inform
      revisions in public education initiatives.

PMID- 15953221
TI  - Australasian Triage Scale: consumer perspective.
AB  - OBJECTIVES: To determine the ED consumers' level of understanding, acceptance and
      desire for knowledge regarding the Australasian Triage Scale (ATS), and to
      determine the ED staff's attitudes towards open provision of ATS information.
      METHODS: Convenience sampling of 289 ED consumers and 56 staff was undertaken.
      Data were collected by self-administered questionnaires. RESULTS: In total, 289
      consumers (100%) and 45 staff (80.3%) agreed to participate. One hundred and
      forty-seven (50.8%, 95% CI 45.0-56.6) consumers linked triage with determination
      of medical urgency. Two hundred and fourteen (74.0%, 95% CI 68.9-79.1) wanted to
      know their ATS category and 236 (81.7%, 95% CI 77.1-86.1) wanted ongoing waiting
      time information. Only 114 (39.4%, 95% CI 33.7-45.1) consumers wanted input into
      their triage rating. Staff felt the ATS was fair, but were uncertain about
      providing specific initial and ongoing ATS information. Staff were strongly
      against any consumer input into the triage process. CONCLUSIONS: Patients do not
      understand the ATS well, and would like to be provided with more specific initial
      and ongoing information, but staff uncertainty needs to be overcome before
      consumers' wishes can be better addressed.

PMID- 15953222
TI  - Patient delay and use of ambulance by patients with chest pain.
AB  - OBJECTIVE: To identify the reasons why patients with chest pain delay in seeking
      hospital medical care and do or do not use an ambulance. METHODS: One hundred and
      fifty-one patients with an ED diagnosis of acute myocardial infarction or angina
      were interviewed about demographic characteristics, medical history, symptom
      onset, time taken before deciding to call an ambulance or go to hospital (delay
      time) and transport used. Multiple logistic regression determined independent
      predictors of late presentation (delay time>30 min) and ambulance use. RESULTS:
      One hundred and twelve (74.2%, 95% CI 67.0-81.0%) patients delayed more than 30
      min. Independent predictors of late presentation were: seeing a general
      practitioner (GP) (P=0.001), having prior heart problems (P=0.009) and symptoms
      occurring at night (P=0.036). Eighty-one (54.7%, 95% CI 47.0-63.0%) patients used
      an ambulance. Predictors of ambulance use were increased age (P=0.025) and having
      ambulance insurance (P=0.018), although there was interaction between these
      variables. CONCLUSIONS: Education programmes should continue to emphasize that
      chest pain is a potential medical emergency and an ambulance should be called.
      GPs should consider developing an action plan to manage patients presenting with
      chest pain.

PMID- 15953223
TI  - Simple lightweight disposable continuous positive airways pressure mask to
      effectively treat acute pulmonary oedema: randomized controlled trial.
AB  - OBJECTIVE: To compare the novel Boussignac valve continuous positive airways
      pressure (CPAP) delivery mask and a standard closed-circuit Drager CF800 CPAP
      system in the management of acute pulmonary oedema (APO) patients. METHODS: This
      was a randomized controlled trial whereby patients presenting to the ED with APO
      and who met the study criteria received either CPAP via the Boussignac valve
      system or from a standard Drager CF800. Baseline physiological and arterial gas
      data were recorded and repeated at 30 and 60 min after CPAP commenced. The
      primary outcome was mean change in pCO2 at 60 min between the two systems.
      RESULTS: There were 39 evaluable patients (19 Boussignac, 20 Drager). The mean
      change in pCO2 at 60 min compared to baseline was similar in the two groups
      (Boussignac 0.9 kPa vs. Drager 1.2 kPa, mean difference -0.3; 95% CI -1.0-0.5,
      P=0.45). In addition, there were no significant differences at 60 min in regards
      to respiratory rate decrease, Boussignac 17.3/min versus Drager 19.6/min (mean
      difference 1.3; 95% CI -3.3-5.8, P=0.58) or peripheral SaO2 increase, Boussignac
      10.7% versus Drager 14.6% (mean difference -3.9; 95% CI -9.9-2.1, P=0.19). There
      was no significant difference in disposition from the ED or the complication
      rate. CONCLUSIONS: The Boussignac valve system may be an effective lightweight
      disposable method of delivering CPAP to patients with APO. It appears to perform
      as effectively as much larger, more expensive and less transportable equipment.

PMID- 15953224
TI  - Ovarian torsion: 10-year perspective.
AB  - OBJECTIVE: To define the presenting symptoms and clinical progress of surgically
      proven cases of ovarian torsion presenting to a tertiary women's hospital.
      METHODS: A retrospective case review of surgically proven ovarian torsion at The
      Royal Women's Hospital, Melbourne between 8 May 1990 and 8 May 2000. RESULTS:
      Fifty-two cases were identified. Median age at presentation was 33.5 years
      (interquartile range [IQR]: 28.7-39.3). Known risk factors at presentation were
      found in 16 (30.8%, 95% CI: 26.9-34.6%) cases including 6/49 (12.2%, 95% CI 11.1
      12.4%) with ovarian hyperstimulation syndrome. The main clinical features
      included: sudden pain (20/23, 87%, 95% CI 75-98.9%), nausea/vomiting (23/39, 59%,
      95% CI 49.9-68.1%) and palpable abdominal mass (23/37, 62.2%, 95% CI 52.4-71.9%).
      Median symptom duration was 3 days (IQR: 1-7.25). Median time to diagnosis was 22
      h (IQR: 7.8-55.0). The diagnosis was mostly made at surgery (36, 69.2%, 95% CI
      60.5-77.9%) with clinically suspicion in 10 (19.2%, 95% CI 17.2-21.3%) and
      sonographic suspicion/confirmation in six (11.5%, 95% CI 10.5-12.5%) cases.
      Ultrasound was performed in 31 (59.6%, 95% CI 51.7-67.6%) cases. Underlying
      pathologies included: ovarian cysts (27, 51.9%, 95% CI 44.9-59.0%) and tumours
      (16, 30.8%, 95% CI 26.9-34.6%)--mostly benign. Ovarian preservation occurred in
      16 (30.8%, 95% CI 26.9-34.6%) cases with no demonstrable association to patient
      age, time to diagnosis or known risk factors. CONCLUSION: The diagnosis of
      ovarian torsion remains challenging. Clinical characteristics lack sensitivity
      and specificity and ultrasound diagnosis is not definitive. Laparoscopy remains
      the investigation of choice. Despite delays in diagnosis this study demonstrates
      relatively high ovarian salvage rates compared with most published data.

PMID- 15953225
TI  - Emergency weight estimation in Pacific Island and Maori children who are large
      for-age.
AB  - OBJECTIVE: Methods to estimate weights of children requiring resuscitation
      appeared to underestimate the weight of Pacific Island and Maori children. This
      study sought to quantify differences between real and estimated weights, study
      links with ethnicity and derive a new estimation method for large-for-age
      children. METHOD: Data were collected prospectively for 3 months. Weights were
      estimated by formulae described by Shann, Leffler, the Advanced Paediatric Life
      Support (APLS) formula, the Oakley resuscitation chart and the Broselow tape.
      RESULTS: Of the 909 children included, 46% were of Pacific Island and 25% were of
      Maori origin. Differences between actual and estimated weights were significantly
      greater (P<0.05) for the Pacific Island group using all methods of estimation.
      Maori differences were significantly greater than European differences using
      Oakley and Broselow methods (P<0.05). The Broselow tape was the method most
      likely to underestimate weight in Pacific Island and Maori children. A new
      formula was derived from non-linear regression analysis, leading to a new chart.
      CONCLUSION: Current emergency methods underestimate weight in Pacific Island and
      Maori children. We recommend a new chart for these children.

PMID- 15953226
TI  - Witnessing invasive paediatric procedures, including resuscitation, in the
      emergency department: a parental perspective.
AB  - OBJECTIVE: To determine whether parents prefer to be present during invasive
      procedures performed on their children in the ED. METHODS: A prospective study
      using a written survey was carried out in the ED of a secondary level regional
      hospital in south-east Queensland. The survey conducted between August 2003 and
      November 2003 consisted of parental demographics, seven theoretical paediatric
      procedural scenarios with increasing level of procedural invasiveness (including
      resuscitation) and reasons for the decisions of parents to either stay with the
      child or leave the room. Parents of children with Australasian Triage Scale (ATS)
      triage category 3, 4 and 5 were surveyed. RESULTS: Of 573 surveys collected, 553
      (96.5%) were completed correctly. The number of parents expressing a desire to be
      present during a procedure performed on their child was 519 (93.9%) for
      phlebotomy or i.v. cannulation of an extremity, 485 (87.7%) for nasogastric tube
      insertion, 461 (83.4%) for lumbar puncture, 464 (83.9%) for urinary catheter
      insertion, 430 (77.8%) for suprapubic bladder aspiration, 519 (93.4%) during
      procedural sedation and 470 (85%) during a resuscitation where the possibility
      existed that their child may die. The most common reason for wanting to be
      present was to provide comfort to their child (542/98%). The most common reason
      for not wanting to be present was a parental concern of getting in the way
      (181/33%). CONCLUSION: Most parents surveyed would want to be present when
      invasive procedures are performed on their children in the ED. With increasing
      invasiveness, parental desire to be present decreased. However, the overwhelming
      majority of parents would want to be in attendance during procedural sedation or
      resuscitation.

PMID- 15953227
TI  - Transthoracic electrical bioimpedance: a means of filling the void?
AB  - OBJECTIVES: To examine the published evidence regarding the use of transthoracic
      electric bioimpedance (TEB) for the non-invasive monitoring of cardiac output in
      the ED. METHOD: Databases of the medical literature, relevant textbooks and the
      Internet were searched for articles regarding TEB. Criteria for inclusion were
      drawn up prior to examination of the articles and included adherence to
      guidelines for comparing methods of clinical measurement. RESULTS: Results are
      discussed under the following headings: technological capability, diagnostic
      accuracy, limitations, range of possible uses, therapeutic impact, impact on
      health care providers, patient outcome and future directions. CONCLUSION: TEB is
      a technique for the non-invasive monitoring of cardiac output whose ease of use,
      continuous data acquisition and versatility suggest it may have a role to play in
      the care of patients in our EDs.

PMID- 15953228
TI  - Update on the fellowship exam and its relation to modern educational principles
      and clinical competency.
AB  - The Australasian College for Emergency Medicine is committed to a long term
      process of quality improvement in the fellowship examination and the training
      programme leading up to it. The process of quality improvement and the rationale
      for current and future processes are not always clear to the fellowship as a
      whole. The present article attempts to update the fellowship on the current
      thinking with regard to the fellowship exam and the work that is being done
      surrounding this and relevant areas. This is related to some modern educational
      assessment principles and terminology. More research is required into the
      relevance of each component of the fellowship exam and its relation to clinical
      competency, key competencies and good clinical practice. Any subsequent changes
      to the exam structure must take into account the evidence and be balanced by what
      is practicable, reasonable and deliverable.

PMID- 15953229
TI  - Processes and impediments in moving patients from the emergency department: pilot
      study.
AB  - OBJECTIVE: To assess the impact of an ED-designed interim orders sheet on patient
      flow through the ED, and the safety of ED-directed admission. METHODS: The flow
      of patients through the ED and inpatient length of stay (IPLOS) was
      retrospectively reviewed on 135 patients who were admitted using interim orders
      and 125 patients who were admitted after inpatient unit review in the ED.
      RESULTS: The median time to admission to the ward in the non-interim orders group
      was 5.7 h (interquartile range [IQR]: 3.8-8.5), with a range from 1.2 to 15.9 h,
      and in the interim orders group was 6.3 h (IQR: 4.8-8.0) with a range from 0.5 to
      22 h (P=0.27). The median IPLOS was 4 days (IQR: 2.0-7.0) in the interim orders
      group, and 4 days (IQR: 2.1-9.0) in the non-interim orders group (P=0.19).
      CONCLUSION: There was no difference in the time to patient admission, or IPLOS,
      with the different processes. Almost half of the average ED stay of adults and
      about one-third of that of paediatric admissions occurred after the decision to
      admit was made. Transfer of patients to the ward without inpatient review is
      appropriate and effective.

PMID- 15953230
TI  - Two cases of amisulpride overdose: a cause for prolonged QT syndrome.
AB  - Two cases of deliberate self-poisoning with 5 g and 3.6 g of amisulpride,
      respectively, are reported. In both cases, QT prolongation and hypocalcaemia were
      noted. The QT prolongation appeared to respond to administration of i.v. calcium
      gluconate.

PMID- 15953231
TI  - Amphetamine-induced movement disorder.
AB  - Recreational use of amphetamines is common in Australia and New Zealand when
      compared with other developed nations. The clinical effects are variable because
      of the potential of these drugs to increase the proportion of different biogenic
      amines in the central nervous system (CNS). The substances affected are
      adrenaline, noradrenaline, serotonin and dopamine. Movement disorders represent
      one of the less common presentations of amphetamine toxicity but one that health
      care workers should be aware of nonetheless.

PMID- 15953233
TI  - Flying doctor.

PMID- 15953232
TI  - Survival of massive gamma-hydroxybutyrate/1,4-butanediol overdose.
AB  - Gamma-hydroxybutyrate and its metabolic precursors gamma butyrolactone and 1,4
      butanediol are widely used recreational drugs known to cause short periods of
      deep sedation with rapid recovery. We present a case of survival with good
      neurological outcome following massive ingestion in which the patient remained
      sedated for 14 h.

PMID- 15953234
TI  - Unusually difficult ring removal from a finger solved using a dental instrument.
AB  - Ring removal is indicated in a number of clinical circumstances to manage or
      prevent tourniquet effect of the digit, or allow access to underlying conditions
      or injuries. A ring made from hardened metal may defy many or all commonly known
      methods of removal. We report a case of unusually difficult removal of a ring of
      hardened metal composition using a dental volvere. We believe the unusual
      circumstances of this case are likely to be repeated on some readers' clinical
      practice, and that this instrument is an appropriate option to consider in such
      cases.

PMID- 15953237
TI  - A 'difficult airway kit' for the emergency department.

PMID- 15953238
TI  - The tetany syndrome at 9000 feet.

PMID- 15953242
TI  - Probiotics: do they have a role in oral medicine and dentistry?
AB  - This review describes current knowledge on probiotic bacteriotherapy from the
      oral health perspective. Recent experimental studies and results from randomized
      controlled trials have shown that certain gut bacteria, in particular species of
      Lactobacillus and Bifidobacterium, may exert beneficial effects in the oral
      cavity by inhibiting cariogenic streptococci and Candida sp. Probiotics have been
      successfully used to control gastro-intestinal diseases. They also appear to
      alleviate symptoms of allergy and diseases with immunological pathology. The
      mechanisms of probiotic action appear to link with colonization resistance and
      immune modulation. Lactic acid bacteria can produce different antimicrobial
      components such as organic acids, hydrogen peroxide, carbon peroxide, diacetyl,
      low molecular weight antimicrobial substances, bacteriocins, and adhesion
      inhibitors, which also affect oral microflora. However, data is still sparse on
      the probiotic action in the oral cavity. More information is needed on the
      colonization of probiotics in the mouth and their possible effect on and within
      oral biofilms. There is every reason to believe that the putative probiotic
      mechanisms of action are the same in the mouth as they are in other parts of the
      gastrointestinal tract. Because of the increasing global problem with
      antimicrobial drug resistance, the concept of probiotic therapy is interesting
      and pertinent, and merits further research in the fields of oral medicine and
      dentistry.

PMID- 15953243
TI  - The immunoreactivity of systemic antibodies to Actinobacillus
      actinomycetemcomitans and Porphyromonas gingivalis in adult periodontitis.
AB  - Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis secrete several
      potent virulence factors and are known to be two of the major periodontal
      pathogens. In the present case-control study, the systemic immunoreactivity to A.
      actinomycetemcomitans exotoxins, cytolethal distending toxin (Cdt) and leukotoxin
      was analyzed in adult subjects with periodontitis and in periodontally healthy
      controls. Furthermore, systemic immunoreactivity to P. gingivalis was analyzed in
      these subjects. Reactivity to the A. actinomycetemcomitans toxins was determined
      in bioassays that quantified neutralizing antibodies, and P. gingivalis
      antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The
      results showed a significantly enhanced immunoreactivity to P. gingivalis in the
      subjects with periodontitis, while the reactivity to A. actinomycetemcomitans
      leukotoxin showed no significant difference between patients and controls.
      However, combined immunoreactivity to leukotoxin and Cdt was more prevalent in
      the subjects with periodontitis than in the controls. In addition,
      immunoreactivity to leukotoxin correlated to periodontitis in men but not in
      women. In conclusion, data from the present study indicate that immunoreactivity
      to P. gingivalis is frequent in adult periodontitis, while the role of A.
      actinomycetemcomitans seems to be more complex and depends on gender of the
      infected subject as well as the virulence of the bacteria.

PMID- 15953244
TI  - How do children with attention deficit hyperactivity disorder interact in a
      clinical dental examination? A video analysis.
AB  - Attention deficit hyperactivity disorder (ADHD) is currently the most common
      behavioural disorder in school-age children. The aim of this study was to perform
      a detailed analysis of behavioural interactions between the dentist and the child
      patient with ADHD. All children born in 1991 (n = 555) in one Swedish
      municipality were screened for attention and learning problems, and assessed for
      ADHD. Twenty-two children with ADHD, and a control group of 47 children without
      attention and learning problems, were included in the study. The dental recall
      visit was recorded on video. The interaction between the dentist and the child
      was analysed in detail and scored as verbal and non-verbal initiatives and
      responses. Compared to the children in the control group, the children with ADHD
      made significantly more initiatives, especially initiatives that did not focus on
      the examination or the dentist. The children with ADHD had fewer verbal responses
      and more missing responses. In conclusion, the problems in communication resulted
      in less two-way communication between the dentist and the children with ADHD than
      the interaction between the dentist and the children in the control group. The
      children with ADHD had particular difficulties staying focused on the
      examination.

PMID- 15953245
TI  - Effects of the tumour necrosis factor-alpha inhibitors pentoxifylline and
      thalidomide in short-term experimental oral mucositis in hamsters.
AB  - Oral mucositis is a frequent side-effect of cancer therapy. A definitive method
      of prophylaxis or treatment is not yet available. As pentoxifylline (PTX) and
      thalidomide (TLD) have been shown to inhibit cytokine synthesis, we studied the
      effects of these cytokine inhibitors in an experimental oral mucositis model.
      Oral mucositis was induced in Golden hamsters by the administration of 5
      fluorouracil (5-FU) followed by mechanical trauma of the cheek pouch. On days 4,
      5, 10, 12, 14 and 16, lesions induced by 5-FU were examined macroscopically and
      microscopically, and the presence and intensity of hyperemia, erythema, edema,
      inflammatory cell infiltration, hemorrhagic areas, ulcers and abscesses were
      recorded. Saline (control), PTX (5, 15, 45 mg kg(-1)) or TLD (10, 30, 90 mg kg(
      1)) were administered daily and animals were killed on day 10 for macroscopic and
      histological analysis and assay of myeloperoxidase (MPO) activity. Animals were
      weighed daily, and total and differential leukocyte counts were performed on
      peripheral blood. PTX and TLD were found to reduce the macroscopic and
      histological parameters of oral mucositis and MPO activity. PTX and TLD also
      reversed peripheral neutrophilia, but only PTX prevented weight loss. The results
      indicate a protective effect of PTX and TLD, suggesting an important role for
      tumour necrosis factor-alpha (TNF-alpha) in the pathophysiology of 5-FU induced
      oral mucositis in hamsters.

PMID- 15953246
TI  - A three-dimensional in vitro model system to study the adaptation of craniofacial
      skeletal muscle following mechanostimulation.
AB  - The aim of this study was to investigate the in vitro response of human
      craniofacial muscle-derived myotubes (primitive/nascent muscle fibres), in three
      dimensional constructs, to strain in vitro to mimic clinical scenarios, using
      expression of the mechanoresponsive gene gelatinase-A/matrix metalloproteinase-2
      (MMP-2) as a marker of remodelling of muscle extracellular matrix. Three
      dimensional (3D) constructs of cells derived from explants of human masseter
      muscle (human craniofacial muscle-derived cells; hCMDC) in collagen sponges were
      subjected to mechanical, uniaxial strain using the Bio-Stretch system. 3D myotube
      constructs were exposed to the strain regimes of rapid ramp stretch (RRS) or
      cyclical ramp strain (CRS) with 7.5% and 15% strain. The activity of MMP-2 was
      assessed by zymography of construct-conditioned medium, whilst lysates of the
      constructs were used to measure creatine phosphokinase (CPK) activity to confirm
      the presence of myotubes in the strained constructs. Scanning electron microscopy
      of the collagen sponges and the CPK assays confirmed the presence of myotubes.
      MMP-2 was expressed by all the samples and controls, but expression was found to
      be significantly higher in those cultures strained continuously (RRS), compared
      to cyclical strain (CRS), and in those strained at 15% compared to 7.5%. Thus,
      MMP-2 expression, and hence extracellular matrix remodelling, is up-regulated in
      response to strain and is dependent upon the amount and type of strain to which
      the muscle is subjected.

PMID- 15953247
TI  - Differential gene expression of collagen-binding small leucine-rich proteoglycans
      and lysyl hydroxylases, during mineralization by MC3T3-E1 cells cultured on
      titanium implant material.
AB  - Titanium implants create a unique ultrastructure (composed of a collagenous zone
      with relatively disorganized fibril morphology) at the bone-implant interface.
      The objective of this study was to investigate the temporal mRNA expression
      patterns, using real-time polymerase chain reaction, of type I collagen (COLI)
      and regulators for collagen fibrillogenesis, collagen-binding small leucine-rich
      proteoglycans (SLRPs) and lysyl hydroxylases (LHs), during mineralization, by
      MC3T3-E1 cells cultured on titanium (Ti). Lysates of the cultures on Ti and on
      plastic wells (Pl) for 10-50 d were used for the quantification of calcium and
      mRNA. Although the onset of calcium accumulation in the cultures on Ti (30-40 d)
      was slower than that of cultures on Pl (20-30 d), the gene expression patterns
      during mineralization were similar in cells cultured on either material. COLI and
      fibromodulin were up-regulated just before the onset of mineralization and then
      down-regulated. Lumican and LH1 were up-regulated just before the onset of
      mineralization and then returned to the baseline level. Decorin and LH2 were up
      regulated at the late mineralization stage. Biglycan was down-regulated once at
      the early mineralization stage and then returned to the original level. LH3 was
      maintained at a steady level throughout. This study suggests actual but distinct
      roles of SLRPs and LHs in the formation of a unique ultrastructure at the bone
      implant interface.

PMID- 15953248
TI  - Relationship between enamel erosion and liquid flow rate.
AB  - The association of severe erosion with certain habits of consuming soft drinks
      prompted a study of erosion in relation to fluid flow. In the main experiments,
      citric acid solution (pH 3.2) was directed at polished enamel surfaces at flow
      rates of 26, 67 or 126 ml min(-1) through outlets of diameters 1.0, 2.6 or 5.0 mm
      for up to 20 min. Erosion depth increased with time of exposure and total volume
      of solution, with increasing flow rate and with decreasing outlet diameter.
      Scanning electron microscopy of acid-treated surfaces and of the subsurface
      enamel indicated that the clearance of dissolution products, rather than the
      mechanical dislodgement of partly dissolved crystal bundles, was the main process
      involved. For an exposure time of 20 min, erosion increased with (liquid
      velocity)(1/4). In a secondary experiment, it was found that the erosive
      potential of a low-erosive drink did not increase with increasing liquid
      velocity. The rapid increase in the rate of erosion caused by citric acid at low
      liquid velocities shows that reproducible stirring is essential for precision and
      intercomparison of in vitro studies. It also accounts for the rapid erosion seen
      when erosive drinks are consumed from a straw placed labial to the anterior
      teeth, or are "swished" between the teeth.

PMID- 15953249
TI  - Caries inhibition around composite restorations by pulsed carbon dioxide laser
      application.
AB  - This in vitro study aimed to evaluate whether laser irradiation of cavity margins
      reduces enamel demineralization around composite restoration. Enamel cavities
      were prepared in 33 human enamel slabs, which were randomly divided into three
      groups. One group was kept as a control, and the cavosurface margin of the
      cavities of the other groups were irradiated, using a CO(2) laser (lambda = 10.6
      microm), at 8 J.cm(-2) or 16 J.cm(-2). The cavities were restored with a resin
      based composite, according to the manufacturer's specifications. Before
      restoration, scanning electron microscopy was performed on one specimen of each
      group. The remaining slabs were submitted to thermal and pH-cycling models.
      Enamel mineral loss, at 50 and 100 microm from the restoration margin, was
      assessed by cross-sectional microhardness analyses. Fusion and melting were
      observed in the irradiated groups. Mineral loss at 50 microm from the restoration
      margin was significantly inhibited in the irradiated groups compared to the
      control group, but at 100 microm from the restoration margin, mineral loss at
      only the highest laser energy density differed statistically from the control
      group. The difference between the irradiated groups was not statistically
      significant at either 50 or 100 microm from the restoration margin. In
      conclusion, irradiation of the cavosurface margin of cavities, using a pulsed
      CO(2) laser, is able to inhibit enamel demineralization around composite
      restorations, and an energy density of 16 J.cm(-2) is efficient, even at 100
      microm from the cavity margin.

PMID- 15953250
TI  - Fluoride release and secondary caries inhibition by adhesive systems on root
      dentine.
AB  - This study tested the fluoride-release rate and the root caries inhibitory effect
      of dental adhesives. In phase 1, the fluoride released from samples (n = 5) of
      the adhesives A (Optibond Solo), B (One-up Bond F), C (Prime & Bond NT), D
      (Tenure Quick), and also of the controls [+] (glass-ionomer cement) and [-] (non
      fluoride releasing adhesive), was quantified on a daily basis during a pH
      cycling, caries-simulating phenomenon. In phase 2, restorations were made in
      bovine root dentine slabs (n = 16) with the same adhesives associated with a non
      fluoridated composite. Control [+] restorations were made entirely with glass
      ionomer cement. Specimens were thermocycled and submitted to the pH-cycling
      regimen. Demineralization areas and the presence of the wall lesion (WL) and the
      inhibition zone (IZ) were determined by polarizing light microscopy in dentine
      adjacent to the restoration. The highest concentration of fluoride was released
      by the control [+]; adhesives A, B and C, also released fluoride. No detectable
      amount of fluoride was released by D or [-]. Smaller areas of demineralization
      were found with control [+], whereas the demineralization areas of adhesives A-D
      and [-] did not differ from each other. No WL was detected, and higher
      percentages of IZ were recorded to [+] and to adhesive A. Although some dental
      adhesives were able to release fluoride, they could not inhibit secondary caries
      development as well as the glass-ionomer cement.

PMID- 15953251
TI  - Color stability of resin-based filling materials after aging when cured with
      plasma or halogen light.
AB  - The influence of curing devices and curing times on the color stability of
      filling resins was investigated by measuring the CIE-Laboratory-values after
      performing dry storage, water storage, and a Suntest (EN ISO 7491). Eight samples
      each of Charisma (CH), Durafill (DU), Definite (DE), and Dyract AP (DY) were
      light cured by using Translux Energy (TE) for 20, 40 or 60 s, or by using Apollo
      95E (AP) for 3, 10 or 20 s. Minor color changes occurred for all dry stored
      materials, devices and curing times. The TE-cured, water-stored samples behaved
      similarly to the dry-stored ones, but the samples cured with AP revealed very
      strong color changes, mainly because of a drastic bleaching process. The
      bleaching of DU was significantly less than that of the other materials, but a
      strong white shift occurred. CH, DE, and DU showed very little (and even
      acceptable) discolorations after the Suntest when TE-cured. DY showed a
      drastically discoloration. All samples cured using AP drastically bleached and
      shifted to white for DU and DY but to dark for DE. In conclusion, the extent of
      discoloration depends on (i) the material, (ii) the test method, (iii) curing
      time, and (iv) the curing device. The halogen light-cured samples performed best.

PMID- 15953252
TI  - Physicochemical evaluation of silica-glass fiber reinforced polymers for
      prosthodontic applications.
AB  - This investigation was designed to formulate silica-glass fiber reinforced
      polymeric materials. Fused silica-glass fibers were chosen for the study. They
      were heat-treated at various temperatures (500 degrees C, 800 degrees C and 1100
      degrees C), silanized, sized and incorporated in two modified resin mixtures (A
      and B). The flexural properties in dry and wet conditions were tested and
      statistically analyzed, and the content of residual methyl methacrylate (MMA)
      monomer, dimensional changes with temperature, water sorption and solubility were
      determined. Woven fibers [36.9% (wt/wt)], heat-treated at 500 degrees C, gave the
      highest strength values for the polymeric composites (an ultimate transverse
      strength of 200 Mpa and a flexural modulus of 10 GPa) compared with the fibers
      heat-treated at other temperatures. There was no statistically significant
      difference in the measured flexural properties between resins A and B regarding
      fiber treatment and water storage time. These fiber composites had a small
      quantity of residual MMA content [0.37 +/- 0.007% (wt/wt)] and very low water
      solubility, indicating good biocompatibility. It was suggested that silica-glass
      fibers could be used for reinforcement as a result of their anticipated good
      qualities in aqueous environments, such as the oral environment.

PMID- 15953255
TI  - Headache research methodology: introduction to the special series.

PMID- 15953253
TI  - Seven-year dentin bond strengths of a total- and self-etch system.
AB  - The aim of this study was to determine the durability of tensile bond strengths
      of a conventional 3-step bonding system (Superbond D-liner Plus) and a self
      etching priming bonding system (Clearfil Liner Bond II) to bovine dentin over a 7
      yr period. Superficial bovine dentin finished with 600-grit SiC paper was bonded
      with one of the two adhesive materials. A 4 mm diameter area was bonded, covered
      with resin composite and stored in 37 degrees C deionized water containing gypsum
      chips and 0.4% sodium azide as an antibacterial. Bonds were stressed in tension
      at a crosshead speed of 1 mm min(-1). Mean bond strengths were observed at 1 d,
      at 1, 3, and 6 months, and at 1, 2, 3, 6 and 7 yr. Ten specimens were tested for
      the first 3 yr and 15 specimens were tested for 6 and 7 yr. The bond strength of
      Superbond D-liner Plus significantly decreased over the 7 yr period, whereas
      Liner Bond II showed a slight but, insignificant, decrease. The fracture mode
      changed with time for Superbond D-liner Plus, but not for Liner Bond II. It was
      concluded that systems which use a strong acid for demineralizing the dentin may
      show greater deterioration of the bond to dentin compared with a self-etching
      priming system.

PMID- 15953256
TI  - Why should physicians care about behavioral research?

PMID- 15953257
TI  - Statistical power and sample size estimation for headache research: an overview
      and power calculation tools.
AB  - The present article reviews the concept of statistical power analysis for
      research designs in headache. First, we present a basic overview of the concepts
      of statistical hypothesis testing. Then we discuss the elements of power analysis
      and, where appropriate, we address conventions for power calculations. We offer,
      for public use, an applied power calculator for two applications that are often
      encountered in headache research. We intend to help headache researchers design
      trials with adequate statistical power by offering a conceptual overview and the
      power calculators. In closing, we briefly address the implications of the present
      trend toward reporting point estimates of effect sizes with confidence levels.

PMID- 15953258
TI  - Allocation of patients to conditions in headache clinical trials: randomization,
      stratification, and treatment matching.
AB  - Assuming control over the allocation of patients to treatment conditions is a
      fundamental element of any comparative clinical trial. There are three critical
      considerations investigators must balance in choosing an allocation scheme:
      reducing bias in patient allocation, producing balanced patient groups across
      treatment arms, and reducing the likelihood of errors attributable to chance
      variation. The authors review the principles of three key approaches to the
      allocation of patients to conditions within clinical trials, and their respective
      advantages with regard to these critical considerations. These allocation methods
      include randomization, stratification, and patient-treatment matching.
      Randomization is fundamental to most clinical trials. Stratification is an
      advanced step in a systematic program of research investigating the efficacy and
      effectiveness of an intervention. If the trial has less than 100 per arm and
      there is a known prognostic factor, stratification is the best choice to ensure
      equal allocation across groups. Treatment matching (tailoring) attempts to match
      the most appropriate treatment to a specific patient based on a priori
      hypotheses. Two techniques used for exploring treatment matching are: patient
      typologies (patient profiling), and aptitude-treatment interactions. Additional
      details pertaining to the rationale for selecting among these various approaches
      to patient allocation is provided, and their methodology is summarized with
      specific consideration for their application within clinical trials of headache
      treatment.

PMID- 15953259
TI  - Outcome measurement in behavioral headache research: headache parameters and
      psychosocial outcomes.
AB  - The experience of pain is complex and includes multiple dimensions or aspects,
      such as sensory and affective (among others). Headache includes not only pain,
      but also associated symptoms that can further diversify the relevant dimensions.
      Subjective ratings of head pain, sampled daily, have come to be regarded as the
      "gold standard" in behavioral headache research. Primary measures of headache
      include the attack frequency or headache days per month. Secondary measures of
      headache may include headache activity/index, headache duration, peak headache
      severity, and/or frequency of severe headaches per month. Secondary measures of
      disability and quality of life include Migraine Disability Assessment (MIDAS),
      Headache Impact Test (HIT), Headache Disability Inventory (HDI). Secondary
      nonheadache measures include medication consumption, psychiatric symptoms, stress
      and coping, treatment satisfaction and preference, side effects, and others.
      Researchers should include not only primary measures of headache, but also
      secondary measures, disability and quality of life, and nonheadache measures. All
      measures should be clearly defined and reported. A baseline period that is
      adequate for each measure needs inclusion and a minimum of 4 weeks is recommended
      for primary headache measures. Specific suggestions for future research
      directions are provided.

PMID- 15953260
TI  - The examination of headache activity using time-series research designs.
AB  - The majority of research conducted on headache has utilized cross-sectional
      designs which preclude the examination of dynamic factors and principally rely on
      group-level effects. The present article describes the application of an
      individual-oriented process model using time-series analytical techniques. The
      blending of a time-series approach with an interactive process model allows
      consideration of the relationships of intra-individual dynamic processes, while
      not precluding the researcher to examine inter-individual differences. The
      authors explore the nature of time-series data and present two necessary
      assumptions underlying the time-series approach. The concept of shock and its
      contribution to headache activity is also presented. The time-series approach is
      not without its problems and two such problems are specifically reported:
      autocorrelation and the distribution of daily observations. The article concludes
      with the presentation of several analytical techniques suited to examine the time
      series interactive process model.

PMID- 15953261
TI  - Time-series features of headache: individual distributions, patterns, and
      predictability of pain.
AB  - OBJECTIVE: This preliminary study employed "within-patient" time-series
      methodology to examine headache symptom distributions (peak, sum) to assess
      predictability of day-to-day headache based on overall pattern, and to better
      characterize distributional properties of headache as they relate to study design
      and statistics in future research. BACKGROUND: Headache symptoms for a given
      patient may vary widely from one day to the next, ranging from days when the
      headache sufferer is asymptomatic to days when he or she is functionally disabled
      with severe headache. Although day-to-day variations are well recognized and
      appreciated clinically, headache is seldom studied using daily (eg, time-series)
      methodology that can elucidate potentially important individual and temporal
      variations. Instead, most headache research has relied upon cross-sectional
      designs aimed at examining group rather than individual effects which may serve
      to mask important individual differences. Additional within-patient time-series
      studies are needed to help identify symptom patterns, clinically meaningful
      patient subgroups, and relationships among precipitants, interventions, and
      outcomes. Such research would be aided by delineation of the distributional and
      temporal properties of key scales (eg, daily headache peak, sum). The present
      research provides such information derived from clinical samples of migraine and
      tension-type headache sufferers, laying a foundation for future time-series
      research. METHODS: Twenty-five migraine and 24 tension-type headache sufferers
      prospectively recorded daily headache activity for 1 month. Individual headache
      distributions were generated and examined individually and by diagnostic group.
      Predictability for headache was analyzed case by case and summarized by
      diagnostic group. RESULTS: The study determined the degree to which individual
      patients' headache activity distributions deviate from normality (skewness,
      kurtosis). For migraine and tension-type headache, individual patients' headache
      patterns were distinctly bimodal in nature. Notably, headache patterns with the
      lowest frequency were the most bimodal, and as frequency increased, the
      distributions tended to more closely approximate normal. Patterns were also
      detailed according to measures of predictability for headache (trends,
      autocorrelation). Generally, headache days tended to cluster together for both
      tension-type and migraine (positive autocorrelation) with headache on day 1 being
      a good predictor of headache on day 2. CONCLUSIONS: To the authors' knowledge,
      this is the first study to utilize time-series methodology to characterize
      individual patients' headache distributions and temporal patterns and to
      empirically address predictability in this manner. The bimodal distributions
      noted among less frequent headache patterns would suggest that basic assumptions
      underlying the use of inferential statistics may be violated when examining intra
      individual relationships. Time-series research promises to yield unique insights
      into patterns, precipitants, and impact of headache disorders, but future
      research must address both the large degree of individual differences in headache
      and the account for the unique types of statistical distributions among
      individual headache sufferers.

PMID- 15953262
TI  - Methodological issues in systematic reviews of headache trials: adapting
      historical diagnostic classifications and outcome measures to present-day
      standards.
AB  - Recent efforts to make headache diagnostic classification and clinical trial
      methodology more consistent provide valuable advice to trialists generating new
      evidence on effectiveness of treatments for headache; however, interpreting older
      trials that do not conform to new standards remains problematic. Systematic
      reviewers seeking to utilize historical data can adapt currently recommended
      diagnostic classification and clinical trial methodological approaches to
      interpret all available data relative to current standards. In evaluating study
      populations, systematic reviewers can: (i) use available data to attempt to map
      study populations to diagnoses in the new International Classification of
      Headache Disorders; and (ii) stratify analyses based on the extent to which study
      populations are precisely specified. In evaluating outcome measures, systematic
      reviewers can: (i) summarize prevention studies using headache frequency,
      incorporating headache index in a stratified analysis if headache frequency is
      not available; (ii) summarize acute treatment studies using pain-free response as
      reported in directly measured headache improvement or headache severity outcomes;
      and (iii) avoid analysis of recurrence or relapse data not conforming to the
      sustained pain-free response definition.

PMID- 15953263
TI  - Behavioral headache research: methodologic considerations and research design
      alternatives.
AB  - Behavioral headache treatments have garnered solid empirical support in recent
      years, but there is substantial opportunity to strengthen the next generation of
      studies with improved methods and consistency across studies. Recently,
      Guidelines for Trials of Behavioral Treatments for Recurrent Headache were
      published to facilitate the production of high-quality research. The present
      article compliments the guidelines with a discussion of methodologic and research
      design considerations. Since there is no research design that is applicable in
      every situation, selecting an appropriate research design is fundamental to
      producing meaningful results. Investigators in behavioral headache and other
      areas of research consider the developmental phase of the research, the principle
      objectives of the project, and the sources of error or alternative
      interpretations in selecting a design. Phases of clinical trials typically
      include pilot studies, efficacy studies, and effectiveness studies. These trials
      may be categorized as primarily pragmatic or explanatory. The most appropriate
      research designs for these different phases and different objectives vary on such
      characteristics as sample size and assignment to condition, types of control
      conditions, periods or frequency of measurement, and the dimensions along which
      comparisons are made. A research design also must fit within constraints on
      available resources. There are a large number of potential research designs that
      can be used and considering these characteristics allows selection of appropriate
      research designs.

PMID- 15953264
TI  - Behavioral research and the double-blind placebo-controlled methodology:
      challenges in applying the biomedical standard to behavioral headache research.
AB  - The randomized, double-blind, placebo-controlled experimental design has
      prevailed as the "gold standard" in biomedical research, intended to control
      potential bias in patient/group assignment, investigator allegiance, patient
      expectations, and nonspecific therapeutic effects. Properly executed, such
      designs ensure a study's internal validity and allow differential group outcomes
      to be attributed to the active treatment. These controlled trials generally yield
      more conservative outcomes than open trials and case reports and establish
      efficacy in pharmaceutical research. In meta-analytic reviews, studies are often
      assigned quality scores based in part on the degree to which they meet this
      scientific standard. Applying the biomedical research design standards for
      blinding and placebo control to clinical trials evaluating behavioral and other
      nonpharmacologic headache treatment nearly always is either infeasible or simply
      not possible. Only rarely is blinding meaningfully achievable in administration
      of behavioral or psychological therapies. Various "psychological placebo" control
      conditions have been forwarded in behavioral studies (eg, sham treatments,
      pseudomeditation), but these controls are incapable of emulating an inert control
      condition comparable to that of the pill placebo in pharmacologic research, and
      they are best reserved for studies examining the mechanisms whereby an
      intervention produces improvement. This article reviews the conceptual and
      procedural challenges in applying the standard pharmaceutical clinical trials
      research design to behavioral headache research as well as implications for meta
      analyses across studies of various treatment modalities.

PMID- 15953265
TI  - Methodological issues in clinical trials of drug and behavior therapies.
AB  - Trials that compare drug and behavior therapies or evaluate combination therapy
      raise special methodological issues. This article reviews these methodological
      issues and, where possible, offers guidelines for addressing them. Sources of
      bias in the selection and recruitment of participants and in the measurement of
      treatment outcomes are discussed. In addition, methodological problems presented
      by the differing structures of behavior and drug therapy, by confounding
      variables, such as allegiance effects, differential expectations and preferences
      for drug or behavior therapy, and differential adherence with drug or behavior
      therapy also are reviewed. Issues in the selection of appropriate control groups
      are also discussed.

PMID- 15953266
TI  - Headache and psychiatric comorbidity: historical context, clinical implications,
      and research relevance.
AB  - The comorbidity of headache and psychiatric disorders is a well-recognized
      clinical phenomenon warranting further systematic research. Affective disorders
      occur with at least three-fold greater frequency among migraineurs than among the
      general population, and the prevalence increases in clinical populations,
      especially with chronic daily headache. When present, psychiatric comorbidity
      complicates headache management and portends a poorer prognosis for headache
      treatment. However, the relationship between headache and psychopathology has
      historically been misunderstood, and measures of psychopathology have not always
      met the standard of formal Diagnostic and Statistical Manual of Mental Disorders,
      4th ed. (DSM-IV) criteria. In some cases, headache has been inappropriately
      attributed to psychological or psychiatric features, based on anecdotal
      observations. The challenge for future studies is to employ research methods and
      designs that accurately identify and classify the subset of headache patients
      with psychiatric disorders, evaluate their impact on headache symptoms and
      treatment, and identify optimal behavioral and pharmacologic treatment
      strategies. This article offers methodological considerations and recommendations
      for future research including: (i) ascribing dual-International Classification of
      Headache Disorders, 2nd ed. (ICHD-2) headache and DSM-IV psychiatric diagnoses
      according to reliable and valid diagnostic criteria, (ii) differentiating
      subclinical levels of depression and anxiety from major psychiatric disorders,
      (iii) encouraging validation studies of the recently published ICHD-2 diagnoses
      for "headache attributed to psychiatric disorder," (iv) expanding epidemiological
      research to address the range of DSM-IV Axis I and II psychiatric diagnoses among
      various headache populations, (v) identifying relevant psychiatric and behavioral
      mediator/moderator variables, and (vi) developing empirically based screening and
      treatment algorithms.

PMID- 15953267
TI  - Efficacy and effectiveness approaches in behavioral treatment trials.
AB  - The objective is to clarify the distinction between efficacy and effectiveness
      approaches and to discuss how these approaches can be used in a complementary way
      in the development, evaluation, and implementation of behavioral treatments for
      primary headache in various settings. Efficacy studies, with an emphasis on
      internal validity, are experiments that evaluate treatment response in an ideal,
      highly controlled research environment. Despite their methodological strengths,
      efficacy studies are limited in their ability to estimate the treatment effects
      that can be expected in clinical practice settings. Effectiveness studies, with
      an emphasis on external validity, are outcome studies with less controls that
      evaluate treatment response in settings more representative of clinical practice.
      Effectiveness studies, however, are limited in their ability to determine the
      causal link between treatment and response. Based on the four-phase model used in
      new drug development, a three-phase linear progression model is presented for
      behavioral treatment studies. This model provides for pilot testing, efficacy
      testing, and effectiveness testing of behavioral treatments so that there is
      appropriate evaluation from initial promise of a developing treatment to
      implementation and dissemination to various treatment delivery settings.

PMID- 15953268
TI  - Moderators and mediators of behavioral treatment for headache.
AB  - Although work has been done establishing the efficacy of behavioral treatments
      for headache, almost no work has been done using appropriate methodology to
      evaluate what types of patients in which settings (termed "moderators") are
      likely to benefit from treatment and what treatment components account for
      treatment response (termed "mediators"). The current article provides an overview
      of moderators and mediators and their assessment and analysis as they pertain to
      clinical trials. The article also discusses the need for moderator and mediator
      hypotheses to be theory driven. A brief consideration of potential moderators and
      mediators of behavioral treatment for headache is then presented. The article
      concludes with a discussion of methodological issues to be addressed when
      conducting moderator and mediator analysis for behavioral treatment for headache.

PMID- 15953269
TI  - Methodological considerations in research with special populations: children and
      adolescents.
AB  - Headache occurs across the lifespan, but limited attention has been devoted to
      children and adolescents. This article discusses pertinent methodological
      considerations when conducting behavioral research with pediatric populations.
      Issues needing special consideration when working with children and adolescents
      involve ethics, sample characterization, headache diagnosis, treatment
      administration, and outcome measurement. Available literature is reviewed and
      specific recommendations are offered when possible.

PMID- 15953270
TI  - Future directions in behavioral headache research: applications for an evolving
      health care environment.
AB  - Three decades of research has produced effective behavioral treatments for
      migraine and tension-type headache, yet the full fruition of this research has
      not been realized. Further development and dissemination of behavioral treatments
      is needed to impact the large numbers of those with headache who potentially
      could benefit from these interventions. At the same time, an evolving health care
      environment challenges researchers and providers to employ greater efficiency and
      innovation in managing all chronic disorders. Hopefully, the recently published
      clinical trials guidelines for behavioral headache research will serve as a
      catalyst for production of quality empiricism that, in turn, will generate
      enhanced behavioral strategies and will optimize health care resource
      utilization. This article describes 10 areas of critical needs and research
      priorities for behavioral headache research, including: replication and extension
      of seminal studies using improved methodology; analysis of barriers to
      implementation of behavioral treatments; development of referral and treatment
      algorithms; behavioral compliance facilitation with medical interventions;
      development of a headache self-management model; integration of behavioral
      intervention within traditional medical practice; identification and management
      of comorbid psychopathology among headache patients; prevention of disease
      progression; analysis of behavioral therapeutic mechanisms, and development of
      innovative treatment formats and applications of information technologies.

PMID- 15953271
TI  - Headache research methodology.

PMID- 15953272
TI  - Treating early versus treating mild: timing of migraine prescription medications
      among patients with diagnosed migraine.
AB  - INTRODUCTION: Although research suggests that early treatment of migraine
      headache when the pain is mild results in better outcomes for patients, many
      patients delay taking their acute-migraine medication until their headaches are
      moderate or severe. Understanding when and why patients use their migraine
      medications is an important first step to improve migraine management. METHODS: A
      prospective observational study, conducted at a major national retail pharmacy
      chain with stores across the United States between April 2001 and November 2002,
      enrolled men and women between 18 and 55 years of age with a physician diagnosis
      of migraine with or without aura. Baseline data on 690 patients included patient
      demographics, migraine history, medication use, tendency to avoid or delay
      treatment of a migraine attack, and reasons for delaying treatment. Reasons for
      delaying treatment were assessed via a checklist of nine potential reasons. In
      the follow-up survey completed after treatment of the next migraine attack,
      patients reported the timing of medication use in relation to pain onset and the
      severity of the migraine headache at the time they took the medication. RESULTS:
      Despite the severity of their typical migraine attacks, approximately 49% of the
      respondents answered, "yes" to the question, "Do you often avoid or delay taking
      your migraine medications when you start to experience a migraine attack?" The
      two most common rationales for avoiding or delaying treatment were "wanting to
      wait and see if it is really a migraine attack" (69%) followed by "only want to
      take medications if it is a severe attack" (46%). In the follow-up survey,
      regardless of medication used, about 85% of patients did not treat their next
      migraine attack until the headache pain was moderate or severe, although 74%
      treated within 1 hour of pain onset. CONCLUSION: These results suggest that
      patients with migraine often delay their treatment until they have identified
      their attack as a migraine. In addition, while many patients treated their follow
      up headache early, they did not treat when the pain was mild. This suggests that
      there is an opportunity for physicians to educate their migraine patients on how
      to differentiate migraine from other headache types and about when and how to use
      their acute-migraine medication.

PMID- 15953273
TI  - Cortical inhibition is reduced in chronic and episodic migraine and demonstrates
      a spectrum of illness.
AB  - BACKGROUND: The pathophysiological relationship between episodic migraine and
      chronic migraine is not fully understood. We aimed to examine transcranial
      magnetic stimulation (TMS) indices of cortical excitability in patients with
      episodic migraine (EM) and probable chronic migraine (PCM), and matched controls.
      METHODS: Cortical excitability was assessed at baseline with two well-established
      methods: phosphene thresholds (PT) and magnetic suppression of perceptual
      accuracy (MSPA) profiles. Five EM patients, five PCM patients, and five normal
      controls participated in the main study. In addition, two patients were
      reassessed after 30 days of treatment with topiramate. RESULTS: Both PT and MPSA
      measures were consistent in indicating a continuum of excitability across the
      three groups: PCM patients had the highest excitability, followed by EM, then
      controls. In the two treated patients MPSA profiles appeared to normalize at a
      100 mg dosage. CONCLUSIONS: Patients with PCM appear to be characterized by very
      high cortical excitability. This may contribute to their greatly increased attack
      frequency. TMS-based methods will be important for future research examining the
      evolution of chronic migraine from episodic migraine over time.

PMID- 15953274
TI  - Disability pattern in chronic migraine with medication overuse: a comparison with
      migraine without aura.
AB  - OBJECTIVES: To assess headache-related disability in chronic migraine with
      medication overuse (CMO), as defined by Silberstein and Lipton (1996, 2001) in
      comparison to that caused by migraine without aura, investigating similarities
      and differences in disability patterns in these two conditions. BACKGROUND: It is
      well known that migraine has a marked impact on daily activities. Less
      information is available on the functional consequences of chronic migraine.
      METHODS: This was a prospective study on 247 patients with CMO and 264 with
      migraine without aura. All completed the validated Italian version of the
      Migraine Disability Assessment questionnaire (MIDAS). The MIDAS total score and
      scores of each question (investigating total or partial inability to perform
      different daily activities) were evaluated, and compared in the two groups using
      the Mann-Whitney rank sum test. We also evaluated the number of missed days
      (question 1) and days with significantly reduced effectiveness at work (question
      2) and in nonwork activities (questions 3, 4, and 5), using descriptive
      statistics. RESULTS: MIDAS total score in the CMO group was rather high (mean
      84.1, median 70) and significantly higher than in the migraine group (mean 23.4,
      median 19). CMO patients also reported higher scores than migraine patients in
      MIDAS questions investigating disability in different domains, the differences
      being highly significant for questions 3, 4, and 5. In both CMO and migraine the
      number of days with total or significant disability in nonwork activities was
      higher than the number of days with total or significant disability in work
      activities, and days spent at work with significantly reduced effectiveness were
      more than work days missed. CONCLUSIONS: Our findings show that CMO has a
      profound effect on patients' daily functioning. They suggest that differences
      between CMO and migraine are mainly quantitative, while the two groups are
      similar in terms of disability pattern. These results are consistent with the
      fact that CMO may be an evolution of episodic migraine, characterized by increase
      in headache frequency and more evident disability in performing different daily
      duties.

PMID- 15953276
TI  - Patients' management of migraine and chronic daily headache: a study of the
      members of the Migraine Action Association (United Kingdom).
AB  - BACKGROUND: Many strategies are available to treat and prevent migraine and
      chronic daily headache (CDH). Broadly these strategies can be divided into four
      groups, including (i) health care consultations, (ii) medication and alternative
      remedies, (iii) general (acute and prophylactic) strategies, and (iv) social
      support. OBJECTIVE: This study aimed to compare headache management between
      migraine (MO), migraine with aura (MA), and those with CDH over the last 12
      months. DESIGN: A postal questionnaire was sent to 887 members of the Migraine
      Action Association (MAA). The response rate was 60.5% (n=537), and 438
      questionnaires were included in the analysis. Migraine (n=117) and MA (n=239)
      patients were classed according to the International Headache Society (IHS). CDH
      (n=82) was diagnosed when respondents had 15 or more headache days per month.
      Descriptive tests, analysis of variances (ANOVAs), chi2, and Kruskal-Wallis tests
      were used for statistical analysis (P<.05). RESULTS: The three groups did not
      differ in age, gender, ethnicity, level of education, and employment status.
      Significant differences in management strategies between the groups were found in
      the number of respondents who had consulted headache specialists (P=.002) and
      neurologists (P=.004), the number and types of acute medications (eg, triptans,
      P=.002), the use of antidepressants (P=.004), and some acute and prophylactic
      avoidance techniques. Although, no significant differences between the groups
      were found in the use of other health professionals (eg, GP), alternative health
      professionals, general acute management, and the use of social support, they all
      actively used these strategies. CONCLUSIONS: The respondents of this study were
      active users of management strategies that are based on a combination of health
      care consultations, medication and alternative remedies, general management, and
      social support. In comparison to previous findings, the respondents in this study
      frequently reported higher use of management strategies (such as the use of
      triptans), which may be related to this group of patients being better informed
      about headache management than those with headache within the general population.
      Thus, the findings may not be representative for the general population, but they
      give an indication of the influence and importance of headache-related education
      carried out by patient organizations such as the MAA.

PMID- 15953275
TI  - Depressive symptoms and insecure attachment as predictors of disability in a
      clinical population of patients with episodic and chronic migraine.
AB  - OBJECTIVES: To define predictors of migraine-related disability in patients with
      episodic and chronic migraine referred to a specialty migraine clinic, focusing
      on depressive symptoms and insecure attachment style that, because of their
      association with responses to pain and physical illness, might be predictive of
      greater migraine-related disability. BACKGROUND: The Migraine Disability
      Assessment questionnaire (MIDAS) has proved to be a reliable and easy-to-use
      instrument to assess migraine-related disability. As clinicians are increasingly
      using MIDAS in their diagnostic and treatment decisions for patient care, an
      understanding of the factors influencing migraine-related disability is essential
      for a rationale use of such an instrument. METHODS: Two-hundred patients
      suffering from episodic migraine without aura (EM), and chronic migraine (CM)
      with and without medication overuse, and referred to a specialty headache clinic
      were evaluated using the MIDAS, the Beck Depression Inventory (BDI), and the
      Attachment Style Questionnaire (ASQ). Diagnosis of episodic and chronic migraine
      was operationally defined according to the International Headache Society (IHS)
      and Silberstein-Lipton criteria. RESULTS: Multiple regression analysis showed
      that, in the total sample, disability was higher in those patients with CM, more
      severe depressive symptoms, an insecure style of attachment (as reflected by a
      lower score on the ASQ confidence scale), and experiencing more severe headache
      pain intensity. In the subgroup of patients with episodic migraine, an insecure
      style of attachment emerged as the most significant predictor of disability
      (other significant predictors were female sex and number of headache days per
      month). In contrast, in the subgroup of patients with CM, the only significant
      predictor of the total MIDAS score was a greater severity of depressive symptoms.
      CONCLUSIONS: Our findings demonstrate the relevance of attachment style, an
      enduring psychological trait not evaluated in previous studies, in influencing
      the disability level in patients with migraine and confirm the role of comorbid
      depressive symptoms in modulating the impact of migraine on every day
      functioning.

PMID- 15953277
TI  - The classification of chronic daily headache in adolescents--a comparison between
      the second edition of the international classification of headache disorders and
      alternative diagnostic criteria.
AB  - OBJECTIVES: To compare the second edition of the International Classification of
      Headache Disorders (ICHD-2) and the Silberstein-Lipton (S-L) criteria in the
      classification of adolescents with chronic daily headache (CDH). METHODS: We
      reviewed the clinical records and the headache diaries of 170 adolescents (13 to
      17 years) seen between 1998 and 2003 at a headache center. Relevant information
      was transferred to a standardized form that included operational criteria for the
      ICHD-2. CDH subtypes were classified according the criteria proposed by S-L into
      transformed migraine (TM) with (TM+) and without medication overuse (TM-),
      chronic tension-type headache (CTTH), new daily persistent headache (NDPH), and
      hemicrania continua (HC). RESULTS: From the 69 patients with TM- according the S
      L criteria, most (71%) could be classified as chronic migraine (CM), while a
      minority of patients required a combination of diagnosis, mainly migraine and
      CTTH (14.4%). Of the patients with TM+, just 39.6% met the criteria for probable
      CM (PCM) with probable medication overuse (PMO). If instead of 15 migraine days
      per month, we considered 15 or more days of migraine or probable migraine, 84% of
      the subjects with TM- and 68.7% of those with TM+ could be classified. Of the 27
      subjects classified as NDPH without medication overuse according to the S-L
      system, the majority (51.2%) were also classified as NDPH according the ICHD-2.
      Interestingly, three (11.1% of the subjects with NDPH without medication overuse)
      were classified as CM in the ICHD-2 because these patients had an abrupt onset of
      15 or more days of migraine per month. All patients with NDPH with medication
      overuse according to the S-L criteria required a combination of diagnoses in the
      ICHD-2. All subjects with CTTH received a single diagnosis in both classification
      systems. CONCLUSIONS: (i) Among adolescents with TM, the majority (58.1%) could
      be classified as CM, according to the ICHD-2. These results were driven by TM
      without medication overuse. (ii) If the ICHD-2 criteria for CM are revised to
      require 15 days of migraine or probable migraine, the proportion of patients with
      TM- who meet the criteria for CM increases from 71% to 84%; for TM+, the
      proportion with probable chronic migraine and PMO increases from 30% to 68%.
      (iii) About half of the patients with NDPH according to the S-L criteria have too
      many migraine features to meet ICHD-2 criteria for NDPH.

PMID- 15953278
TI  - Comorbidity of psychiatric and behavioral disorders in pediatric migraine.
AB  - OBJECTIVE: To determine whether behavioral and psychiatric disorders occur more
      frequently in school-age children with migraine headache. To also elucidate
      treatment response related to comorbid psychiatric or behavioral diagnosis.
      BACKGROUND: Recurrent migraine headaches are common in school-age children.
      Concurrent behavioral or psychiatric diagnoses could significantly impact
      headache frequency, severity, and response to treatment. METHODS: Healthy
      children from 6 to 17 years of age presenting to our headache clinic with
      migraine headache according to International Headache Society (IHS) criteria were
      identified. Parents/guardians were asked to complete the Child Symptom Inventory,
      4th edition (CSI-4) after written informed consent. Children with positive rating
      scales underwent psychological interviews for confirmatory diagnosis. Results
      were compared to controls. Headache patients were assigned our usual treatment
      paradigm. Response regarding headache frequency was assessed at 3 months.
      RESULTS: A total of 47 patients were diagnosed with migraine headaches. The mean
      age was 10.55 years. Thirty controls were identified. After completing the CSI-4
      and confirmatory psychological interview, 14 of 47 headache patients fulfilled
      Diagnostic and Statistical Manual (DSM-4) criteria for a psychiatric or
      behavioral disorder. Oppositional defiant disorder (ODD) was significantly
      represented among children with migraine compared to the control group of
      children. Headache patients improved significantly post-treatment regarding their
      headache frequencies regardless of comorbid psychiatric or behavioral disorder.
      No significant differences were noted between boys and girls regarding diagnoses
      or treatment outcome. CONCLUSION: ODD was a significant comorbidity in our
      headache population. Although families complained of significant behavioral
      symptomatology in their children, most of these symptoms did not qualify their
      children for a psychiatric diagnosis and may be related to the stressors of
      headache on social/school disruption.

PMID- 15953279
TI  - The headache of SAH responds to sumatriptan.
AB  - We report the first case of the headache of subarachnoid hemorrhage (SAH)
      possibly responding to a triptan. Recent evidence suggests that triptans block
      transmission from the trigeminal nerve to second-order neurons in the trigeminal
      nucleus caudalis; thus, any meningeal nociceptive process would be aborted. The
      triptans and ergots are not specific for migraine, but for any process that
      activates trigeminal fibers, including migraine, cluster headache, SAH, and
      meningitis. The failure to respond in the reported cases of meningitis may be due
      to sensitization.

PMID- 15953280
TI  - The perils of misinterpreting a treatment response.

PMID- 15953281
TI  - Are triptans effective and safe when taken during the aura phase of migraine?

PMID- 15953282
TI  - A case of postprandial cluster-like headache with prolactinoma: dramatic response
      to cabergoline.
AB  - A 17-year-old boy without a significant past medical history presented with
      recurrent cluster-like headaches induced by meals for 3 years. Magnetic resonance
      images showed a pituitary tumor. Just after starting treatment with cabergoline,
      the headaches resolved completely and the patient has been absolutely free from
      such headache attacks for 2 years.

PMID- 15953283
TI  - Filum ependymoma mimicking spontaneous intracranial hypotension.
AB  - A 34-year-old man with a 2-week history of orthostatic headaches and a "dry tap"
      at lumbar puncture was found to have a lumbar intradural mass on magnetic
      resonance imaging (MRI) examination. A myxopapillary ependymoma was resected and
      the patient's headache completely resolved. The combination of spontaneous
      orthostatic headaches and a "dry tap" at the time of lumbar puncture does not
      always indicate the presence of a spontaneous cerebrospinal fluid (CSF) leak and
      intracranial hypotension.

PMID- 15953284
TI  - Atypical headache after prolonged treatment with nasal continuous positive airway
      pressure.
AB  - We report a case of atraumatic pneumocephalus associated with prolonged use of
      nasal continuous positive airway pressure. Initial symptoms included headache,
      ataxia, vertigo, and a "gurgling" sensation in the head; and a CT image showed
      small air bubbles along the falx of cerebrum and adjacent to the temporal
      epidural spaces bilaterally. Although no evidence of cerebrospinal fluid (CSF)
      leak was either reported by the patient or found at initial clinical examination,
      subsequent nasal discharge tested positive for beta2-transferrin, a finding
      consistent with CSF leak in the paranasal sinus region or through the cribriform
      plate. To try to prevent infection from an open communication between the
      paranasal sinuses and intracranial structures, an attempt should be made to
      localize the anatomic defect.

PMID- 15953285
TI  - Ocular compression maneuver aborts benign cough-induced headache.
AB  - Benign cough-induced headache is a short-lasting cranial discomfort. The
      therapeutic role of lumbar puncture (LP) or indomethacin in benign patients with
      benign cough-induced headache patients is debatable. Transient ocular compression
      (OC) raises intraocular pressure (IOP) and can limit the impact of cough-induced
      choroidal venous congestion. A self-applied maneuver that instantaneously aborts
      cough-induced headache is described in two patients. The effect of this maneuver
      supports a recent hypothesis that cough-induced headache may be due to ocular
      choroidal venous congestion and mechanical antidromic trigeminal nerve
      activation. The OC maneuver has several potential complications and its self
      application in benign cough-induced headache should be regarded as an
      experimental procedure until more data regarding its efficacy and safety become
      available.

PMID- 15953286
TI  - Triptans to abort neurological symptoms of prodrome of migraine: fact or fiction?

PMID- 15953287
TI  - Old age of onset in cluster-headache patients.

PMID- 15953288
TI  - Comment: "the premonitory symptoms (prodrome): a tertiary care study of 893
      migraineurs".

PMID- 15953293
TI  - Consistent efficacy, tolerability, and high levels of satisfaction with
      almotriptan 12.5 mg when used to treat multiple migraine attacks in routine
      clinical practice.
AB  - OBJECTIVE: To assess the efficacy, tolerability, and patient satisfaction with
      almotriptan 12.5 mg across multiple migraine attacks in routine clinical
      settings. BACKGROUND: The efficacy and tolerability of almotriptan have been well
      documented in clinical trials. Less information is available about patient
      acceptance of therapy under normal prescribing conditions in routine practice.
      METHODS: This was a prospective, open-label surveillance study conducted on 899
      adults with documented attacks fulfilling the IHS criteria for migraine in
      medical practices of 307 neurologists and primary care physicians across Germany
      from June 2001 to April 2002. Patients were eligible for inclusion in the study
      if they were being treated for the first time with almotriptan. Main outcome
      measures were pain relief, pain free, consistency, tolerability, and satisfaction
      with almotriptan 12.5 mg when used to treat multiple migraine attacks. RESULTS: A
      total of 899 patients with migraine treated 1 (18.4%), 2 (25.9%), or 3 (55.6%)
      migraine attacks with almotriptan for a total of 2131 attacks. Pain relief at 2
      hours was achieved in 84.5% of attacks; pain free was achieved in 41.4%.
      Consistency of almotriptan 12.5 mg (at least 2 out of 3 attacks successfully
      treated) was 87.3%. Most patients (88.5%) indicated that they were "satisfied" or
      "very satisfied" with their treatment with almotriptan and 80.3% of patients
      expressed that almotriptan 12.5 mg therapy was better than their prior therapy.
      Physicians' global assessment of the efficacy of almotriptan 12.5 mg was judged
      to be "good" and "very good" in 87.6% of the patients, and tolerability was
      considered to be "good" and "very good" in 96.3% of patients. More than 92% of
      physicians indicated that they would continue to prescribe almotriptan for their
      patients. CONCLUSION: The high levels of efficacy, consistency, and tolerability
      of almotriptan 12.5 mg observed in this postmarketing surveillance study are not
      only consistent with the findings of controlled clinical trials but also resulted
      in high rates of patient and physician satisfaction with almotriptan and patient
      preference for almotriptan over prior acute treatments, including other triptans.

PMID- 15953294
TI  - Resolution of concentration-response differences in onset of effect between
      subcutaneous and oral sumatriptan.
AB  - OBJECTIVE: To investigate whether the concentration-response relationships for
      onset of effect of oral and subcutaneous (s.c.) sumatriptan differ, and if so,
      then to explore whether a single model for the onset of effect can nonetheless be
      found for multiple dose sizes and both routes of administration. METHODS: Active
      and placebo response rates and mean plasma concentrations were collected from the
      literature for 0 < or =t < or = 2 hours. Plasma concentration-response
      relationships were plotted. Logarithmic models for the onset of effect (ie,
      active response rates), characterized by convexity factor A and location
      parameter B were constructed from the same data. RESULTS: The concentration
      response relationships for s.c. and oral sumatriptan are qualitatively different.
      A single logarithmic model for the onset of effect provides good estimates of
      observed response rates during the first 2 hours post-dose for multiple dose
      sizes after both oral and s.c. routes of administration. The precision of this
      model resides in both its variables. Location parameters for this model differ
      for similar absolute doses by the two routes of administration. However, curve
      convexity (representing rate of onset of effect) is related to absolute dose (and
      hence plasma concentration) in the same way for sumatriptan tablets and
      injections. CONCLUSIONS: No simple plasma concentration-response relationship
      exists that is sufficiently robust to apply to both s.c. and oral sumatriptan.
      There are separate pharmacokinetic-pharmacodynamic relationships for rate of
      onset and extent of effect. The design of exploratory clinical trials for new
      acute therapies for migraine may be more efficient when these factors are
      considered, and these factors may help to describe the gap between experimental
      and ordinary clinical environments.

PMID- 15953295
TI  - Psychometric properties of the HIT-6 among patients in a headache-specialty
      practice.
AB  - OBJECTIVE: To evaluate the performance and score interpretability of the Headache
      Impact Test (HIT-6) questionnaire in a headache patient population. BACKGROUND:
      The HIT-6 is a standardized questionnaire designed to assess headache-related
      disability. Norms have been established using randomly sampled respondents from
      the general population. This study evaluated the psychometric properties of the
      HIT-6 scale among new adult patients who presented for treatment at a university
      headache-specialty practice. METHODS: Participants were 309 new patients who
      presented for treatment at a headache-specialty clinic in an academic medical
      center. RESULTS: Respondents ranged in age from 18 to 91 years, with an average
      age of 41 years (SD = 13 years) and were predominantly female (77%). Over half
      (57%) experienced chronic daily headache. Scores ranged from 38 to 78, with an
      average of 65.6 (SD = 7.0) and the majority (87%) had "severe impact" (60 or
      higher). The scale showed high reliability (alpha= 0.87) and an exploratory
      factor analysis showed large loadings from |0.57| to |0.86| and suggested a
      single disability factor. Scores were moderately negatively correlated with Short
      Form Health Survey (SF-36) subscales, ranging from -0.22 for mental health to 
      0.57 for social functioning. Item response theory analyses showed that half of
      the items functioned well across the disability continuum, while the remaining
      items discriminated between low and high levels of headache impact. CONCLUSIONS:
      These findings suggest that the HIT-6 is useful for assessing headache-related
      disability among patients who seek headache-specialty care.

PMID- 15953296
TI  - Validation of a questionnaire for the detection of cluster headache.
AB  - BACKGROUND: In the absence of biological markers, the diagnosis of cluster
      headache (CH) rests on clinical evidence as reported through ad-hoc interviews.
      OBJECTIVE: The aim of this study was to validate a 16-item self-administered
      questionnaire designed to screen CH cases. METHODS: The questions were based on
      the second edition of the International Headache Society classification (ICHD-II)
      criteria for CH (n = 12) and on specific disease features (n = 3). Answers to
      each question were either "Yes,""No," or "Don't know." The validity of this
      screening tool was assessed using a two-step procedure. In Step 1, the 16
      questions were submitted to 30 healthy subjects with different cultural
      backgrounds to verify content clarity. In Step 2, the questionnaire was given to
      71 patients (32 women and 39 men) aged 15 to 78 years (mean 37.5 years), who were
      seen at the University of Parma Headache Center with a diagnosis of CH (episodic,
      17; chronic, 13), migraine (without aura, 18; with aura, 3), and tension-type
      headache (episodic, 16; chronic, 4) according to the ICHD-II criteria.
      Sensitivity, specificity, and the positive and negative predictive values were
      calculated for each question as measures of validity. RESULTS: Severity,
      unilaterality, and location of pain had the highest sensitivity (100%), but low
      (34.1%) or fairly low specificity (61.0% and 58.5%, respectively). In contrast, a
      positive response to lithium or verapamil had a 66.7% sensitivity and a 97.6%
      specificity. Sensitivity and specificity were 100% and 90.2% for duration of
      attacks (<180 to 240 minutes), and 90.0% and 92.7% for compulsory movements,
      respectively. The best discriminatory pattern for symptom detection was
      unilaterality of pain and the presence of at least five of the following seven
      features: pain severity and location, duration, frequency and daily recurrence of
      attacks, rhinorrhea and restlessness as accompanying symptoms. CONCLUSIONS: Our
      findings confirm that this questionnaire is a useful method for CH screening in
      epidemiological studies.

PMID- 15953297
TI  - Triggers of motion sickness in migraine sufferers.
AB  - OBJECTIVE: To determine whether susceptibility to motion sickness provoked by
      unexpected movement is associated with susceptibility to visually induced motion
      sickness in migraine sufferers. BACKGROUND: Migraine sufferers are unusually
      susceptible to motion sickness, but the mechanism of this susceptibility is not
      well understood. Possibilities include vestibular dysfunction secondary to
      vasomotor disturbances during migraine attacks, hyperexcitability of brainstem
      circuits that produce symptoms of motion sickness and migraine, and heightened
      susceptibility to visual illusions of movement. METHOD: A motion sickness
      susceptibility questionnaire that listed common triggers of motion sickness was
      filled out by 42 migraine sufferers and 39 headache-free controls of similar age
      and sex distribution to migraine sufferers. RESULTS: A greater proportion of
      migraine sufferers than controls reported that traveling in cars and buses,
      reading in the car, using playground equipment, watching wide-screen movies and
      movement simulators, induced motion sickness. However, visually induced motion
      sickness appeared to be independent of motion sickness to most movement-related
      stimuli in migraine sufferers. CONCLUSIONS: The lack of association between
      susceptibility to movement-induced and visually induced motion sickness implies
      that more than one mechanism increases susceptibility to motion sickness in
      migraine sufferers.

PMID- 15953298
TI  - Psychological, sleep, lifestyle, and comorbid associations with headache.
AB  - OBJECTIVE: To investigate the associations of headache occurrence, severity, and
      frequency with psychological, sleep, and lifestyle characteristics, and comorbid
      conditions. BACKGROUND: Whilst associations for individual headache types,
      particularly migraine, have been investigated, possible associations between
      headache of all types and general health characteristics have not been explored.
      METHODS: Cross-sectional postal survey in an adult general population sample
      registered at five general practices in North Staffordshire, UK. RESULTS:
      Headache occurrence was associated with anxiety (odds ratio 4.09, 95% confidence
      interval 3.0, 5.6) and sleep problems (moderate sleep problems OR 3.60, 95% CI
      2.5, 5.0), and the strength of the associations increased with higher levels of
      anxiety and sleep problem. Whilst depression showed an association with headache,
      this was not seen in respondents with depression in the absence of anxiety.
      Headache occurrence was also associated with comorbid pain anywhere in the body
      (OR 2.12, 95% CI 1.7, 2.6), with the strongest associations being for the neck
      and upper body areas compared with other areas. There was no overall link with
      alcohol or caffeine consumption. Increasing severity and frequency of headache
      resulted in stronger associations, and there were strong associations between the
      occurrence, severity, and frequency of headache, and both sleep problems and
      psychological distress. CONCLUSION: Poor sleep and anxiety appear to make a
      substantial contribution to the impact of headache on sufferers' lives in the
      general population.

PMID- 15953299
TI  - The association of brainstem lesions with migraine-like headache: an imaging
      study of multiple sclerosis.
AB  - OBJECTIVE: To determine if the prevalence of migraine-like headache in patients
      with multiple sclerosis (MS) is associated with plaques in the brainstem or in
      other locations. BACKGROUND: There is increasing evidence to suggest that
      periaqueductal gray matter (PAG) plays a role in the pathophysiology of migraine
      headache. There are a few clinical case studies and some experimental evidence in
      support of this observation. METHODS: The study population of patients with
      demyelinating disease was identified by accessing the Department of Radiology
      magnetic resonance imaging (MRI) database accumulated between the years of
      December 1992 and June 2002. A total of 4369 MRI scan reports were available for
      review from that time period. Out of this, 1533 studies were reported to have
      possible demyelinating lesions. Medical records of these patients were reviewed
      to confirm the diagnosis of MS and also to document the headache complaints, if
      any. Two hundred and seventy-seven patients were identified with definite MS. A
      questionnaire was mailed to these patients to obtain additional details regarding
      MS and headache. The questionnaire response rate was 61% (169 of 277). This data
      were added to the information previously obtained from the medical records. The
      MRI films of each patient were examined, documenting location of the plaque,
      rather than the actual number. MRI and clinical data were kept separate until the
      final analysis. The International Headache Society criteria were used to classify
      headache types. RESULTS: There were 207 female and 70 male patients available for
      analysis. Sixty-six percent (182 of 277) of patients were diagnosed with
      remitting-relapsing MS, 17% (47 of 277) with primary progressive MS, and 17% (48
      of 277) with secondary progressive MS. Overall, 55.6% (154 of 277) of patients
      had a complaint of headache. Of these patients, 61.7% (95 of 154) met criteria
      for migraine-like headache, 25.3% (39 of 154) met criteria for tension-type
      headache, and 13% (20 of 154) had features of migraine and tension-type headache.
      MS patients with a plaque within the midbrain/periaqueductal gray matter areas
      had a four-fold increase in migraine-like headaches (odds ratio 3.91, 95%
      confidence interval 2.01 to 7.32; P < .0001), a 2.5-fold increase in tension-type
      headaches (odds ratio 2.58, 95% confidence interval 1.13 to 5.85; P= .02), and a
      2.7-fold increase in combination of migraine and tension-type headaches (odds
      ratio 2.77, 95% confidence interval 0.98 to 7.82; P= .05) when compared to MS
      patients without a midbrain/periaqueductal gray matter lesion. Although not
      statistically significant, MS patients with three or more lesion locations were
      found to be approximately two times more likely to have migraine-like headaches
      compared to MS patients with 0 to 2 locations (3 to 5: odds ratio 2.47, 95%
      confidence interval 0.90 to 6.84; 6 to 8 locations: 1.82, 0.64 to 5.17; > or =9
      locations: 2.41, 0.63 to 9.13). A linear trend was also observed between numbers
      of lesion locations and migraine-like headaches (P= .02). CONCLUSION: The results
      of this study indicate that the presence of a midbrain plaque in patients with MS
      is associated with an increased likelihood of headache with migraine
      characteristics. (Headache 2005;45:670-677).

PMID- 15953300
TI  - Chronic daily headache in children and adolescents.
AB  - OBJECTIVE: To describe the clinical features of children with chronic daily
      headache (CDH) and examine the usefulness of the International Classification of
      Headache Disorders-II. BACKGROUND: Few data are available on chronic daily
      headache and analgesic overuse in children and adolescents and there are no
      specific criteria for headache in children. METHODS: We retrospectively reviewed
      all charts of 79 children and adolescents (<16 years) with headache on > or =15
      days/month presenting to the outpatient clinic of the Department of Neurology of
      the Leiden University Medical Center between 1994 and 2001. We classified their
      headaches according to the International Classification of Headache Disorders-II.
      RESULTS: Fifty-seven (72%) children had chronic daily headache for more than 6
      months, with a duration of more than 4 hours a day in 60% of them. Quality,
      severity, and location of pain varied. Sixty patients (76%) used analgesics, 10
      patients more than one type. Thirteen patients (16%) used analgesics daily. In
      one-third of patients, headache led to frequent school absenteeism and sleeping
      problems. Twenty-eight (35%) patients could be classified, 17 patients (22%) as
      chronic tension-type headache, 5 patients (6%) as chronic migraine, and 6
      patients (8%) as probable medication overuse headache. Fifteen patients (19%) did
      not fit into any category and 36 (46%) could not be classified due to
      insufficient data. CONCLUSIONS: Chronic daily headache in children is a serious
      disorder. A relatively large number of patients overuse medication and it leads
      to frequent school absenteeism and sleeping problems. It remains difficult to
      classify their headaches with the new criteria for headache disorders.

PMID- 15953301
TI  - One-year incidence, course, and outcome predictors of frequent headaches among
      early adolescents.
AB  - OBJECTIVE: To examine the prevalence rate, course, annual incidence, and
      predictors of frequent headaches (at least once a week) in a 1-year longitudinal
      study of a representative school sample of 2355 adolescents aged 12 to 14 years.
      METHODS: Information was gathered by means of questionnaires administered to the
      subjects at school. RESULTS: The overall prevalence estimates of frequent
      headaches, including those subjects reporting another type of frequent pain, were
      8.1% and 8.9% at the two assessment points (T(1) and T(2)), and 3.3% to 4% for
      frequent headaches without other frequent pain complaints. Both forms of frequent
      headaches were about three times more common among girls than boys. Persistence
      of frequent headaches (with possible pain comorbidity) was high, in that more
      than one-third of adolescents reporting frequent headaches continued to have such
      headaches 1 year later. Persistence also increased with age, in particular among
      13- to 14-year-old girls. The overall annual incidence of frequent headaches in
      the whole sample was 6.5%. While incidence was about twice as high among
      adolescent girls than boys, there was a steady increase among girls, whereas the
      rates were stable in boys. The results of multivariate regression analyses showed
      that frequent headaches at 1-year follow-up could be significantly predicted by
      frequent headaches at first assessment, impairment (reduced leisure time
      activities), and high depressive symptom scores, in addition to gender (girls had
      a worse outcome). CONCLUSIONS: Frequent headaches, among girls in early
      adolescence in particular, should be carefully evaluated, and treatment offered
      to those who are impaired in their daily life functioning.

PMID- 15953302
TI  - Relaxation treatment of adolescent headache sufferers: results from a school
      based replication series.
AB  - BACKGROUND: In recent reviews of psychological and drug treatment, relaxation
      training approaches have been found to be efficacious for children and
      adolescents suffering from recurrent tension-type headache (TTH), while
      biofeedback procedures provide effective help for migraine headache sufferers,
      primarily treated in tertiary clinics. OBJECTIVE: In a school-based replication
      series, the effectiveness and efficiency of relaxation training provided within
      school settings were examined, in addition to the effects on various headache
      features and the maintenance of treatment gains at a 6 to 10-month follow-up.
      METHODS: Over a 20-year period, 288 adolescents aged 10 to 18 years participated
      in seven randomized, controlled trials conducted within regular school health
      service settings. Subjects were included if they had suffered from frequent
      migraine or TTHs, or from both headache types for at least 1 year. Various
      formats of standardized relaxation training procedures were contrasted to
      different attention-control (ATCO) approaches or self-monitoring (SM) of
      headaches in prospective diary recordings. RESULTS: The results showed that a
      therapist-administered relaxation approach was superior to self-help or school
      nurse administered relaxation training approaches, ATCO conditions or SM of
      headaches. Students with TTHs responded positively to any form of relaxation
      training, whereas those with frequent migraine responded well only to therapist
      administered relaxation. However, school-nurse administered procedures were found
      to be the most efficient form of relaxation treatment, in particular for
      adolescents suffering from TTHs. Total headache activity, the number of headache
      days and peak headache intensity were significantly reduced after relaxation
      treatment, in addition to medication usage. Treatment gains were well maintained
      at the 6 to 10-month follow-up. CONCLUSION: Therapist-assisted relaxation
      training is an effective treatment for adolescents suffering from frequent TTHs
      or migraine. However, such treatment administered by school-nurses administered
      within school health care settings is an efficient treatment approach for
      adolescents suffering from the most common form of primary headache, ie, TTHs.

PMID- 15953303
TI  - Idiopathic headache in children under six years of age: a follow-up study.
AB  - OBJECTIVE: To assess the evolution of idiopathic headache with early onset and to
      investigate the influence of early somatic disorders, "life events," and
      psychiatric disorders on the onset and the course of headache. We also studied
      the possible prognostic role of gender, headache diagnosis at onset, and history
      of headache in family members on the course of headache. We also investigated the
      applicability of the ICHD-II criteria to idiopathic headache in preschool
      children. METHODS: Prospective evaluation of 25 consecutive headache patients
      referred before the age of 6 years. Headache diagnosis was based on the IHS 1988
      criteria, on the ICHD-II criteria, and on "alternative" clinical criteria [eg,
      duration less than 1 hour in migraine without aura (MWA), less than 30 minutes in
      tension-type headache (TTH)]. All patients were assessed by a structured
      interview to detect early developmental disorders (eg, feeding difficulties or
      sleep disorders) and "life events" (eg, parents' separation and others according
      to DSM-IV). All patients underwent clinical observations and assessment of
      psychiatric comorbidity (ICD-10) by means of interviews and the Child Behaviour
      Check List. All the above-mentioned evaluations were performed at recruitment
      (T0) and at the end of the follow-up period (T1). RESULTS: A total of 25 children
      with headache (12 males; 13 females) were monitored through long-term clinical
      follow-up (mean duration: 4.2 years; range: 2.8 to 6.6 years). The "definite"
      diagnosis of migraine without aura or TTH at T0 was possible in only 6/25 (24%)
      and 9/25 patients (36%) applying the IHS 1988 criteria and the ICHD-II criteria
      respectively, but in 20/25 (80%) applying the "alternative" clinical criteria.
      Evaluation of headache at T1 revealed: remission in 16/25 (64%) patients and
      persistence in 9/25 (36%). At T1, the ICHD-II diagnosis was possible in 100% of
      the children with headache persistence (1/9 migraine without aura and 8/9 TTH)
      and these diagnoses were found to be perfectly concordant with those obtained
      applying the "alternative criteria." Early developmental disorders were present
      in 11/25 children, with a significantly higher prevalence in children with
      headache persistence compared to children showing headache remission (78% vs.
      25%; P < .05). No significant differences were found between patients with
      headache persistence and patients with headache remission with regard to gender,
      history of headache in family members, headache diagnosis at onset, psychiatric
      comorbidity at T0, and with regard to "life events" at both T0 and T1.
      Conversely, the children presenting psychiatric disorders at T1 were more
      frequently affected by headache than those without psychiatric disorders (59% vs.
      15%; P < .05). CONCLUSIONS: Our results suggest that the ICHD-II criteria are too
      restrictive to allow the classification of migraine without aura and TTH in
      preschool children. Nevertheless, a diagnosis based on these criteria was
      possible in all the patients with headache persistence at the end of several
      years' follow-up. We found a significant association between early somatic
      disorders and persistence of headache and also between the presence of
      psychiatric disorders at the end of follow-up and the persistence of headache.
      "Life events," on the other hand, while not showing a statistically significant
      association with the evolution of the headache, may nevertheless influence the
      course of the headache in some patients. Our results suggest that environmental
      and psychological factors play an important role in idiopathic headache with
      onset in preschool age, and thus that the diagnostic-therapeutic approach must
      take these factors into account.

PMID- 15953304
TI  - Traditional and evidence-based acupuncture in headache management: theory,
      mechanism, and practice.
AB  - Acupuncture, traditional Chinese needle therapy, has become widely used for the
      relief of headache. The history of the practice of acupuncture in the United
      States and the theoretical framework for acupuncture in Chinese medicine are
      reviewed. The basic scientific background and clinical application of acupuncture
      in the headache management are discussed.

PMID- 15953305
TI  - Referred pain from the trochlear region in tension-type headache: a myofascial
      trigger point from the superior oblique muscle.
AB  - BACKGROUND: Tension-type headache (TTH) is a prototypical headache in which
      myofascial trigger points (MTrPs) can play an important role. To our knowledge,
      MTrPs in the muscle tissues of the trochlear region, ie, the superior oblique
      muscle (SOM), have not been previously mentioned, and a referred pain pattern
      from this region has never been reported. OBJECTIVE: To describe the referred
      pain from the trochlear area based on the examination of MTrPs in the SOM in
      patients with episodic and chronic TTH (CTTH). DESIGN: A blinded, controlled
      study. METHODS: The trochlear region was examined in 15 patients with CTTH, 15
      patients with episodic TTH (ETTH), and 15 control subjects. Referred pain
      elicited by different maneuvers performed during manual palpation, ie, maintained
      pressure, active muscle contraction, and stretching of the muscle, was assessed
      with a visual analogue scale. Patients with ETTH were examined on days when they
      were headache-free, whereas CTTH patients were examined on days in which headache
      intensity was less than 4 points on a 10-cm horizontal visual analogue scale.
      RESULTS: Eighty-six percent of patients with CTTH and 60% with ETTH had referred
      pain that originated from MTrPs in the SOM, while only 27% of the controls
      reported referred pain. This pain was perceived as a deep ache located at the
      retro-orbital region, sometimes extending to the supra-orbital region or the homo
      lateral forehead. Pain intensity was greater in CTTH patients than in ETTH
      patients or control subjects (P < .001). CONCLUSIONS: MTrPs in the SOM may evoke
      a typical referred pain pattern in patients with TTH. The presence of a
      myofascial disorder in the trochlear region might contribute to the pathogenesis
      of TTH.

PMID- 15953306
TI  - Physical treatments for headache: a structured review.
AB  - BACKGROUND: Primary headache disorders, especially migraine, are commonly
      accompanied by neck pain or other symptoms. Because of this, physical therapy
      (PT) and other physical treatments are often prescribed. This review updates and
      synthesizes published clinical trial evidence, systematic reviews, and case
      series regarding the efficacy of selected physical modalities in the treatment of
      primary headache disorders. METHODS: The National Library of Medicine (MEDLINE),
      The Cochrane Library, and other sources of information were searched through June
      2004 to identify clinical studies, systematic reviews, case series, or other
      information published in English that assessed the treatment of headache or
      migraine with chiropractic, osteopathic, PT, or massage interventions. RESULTS:
      PT is more effective than massage therapy or acupuncture for the treatment of TTH
      and appears to be most beneficial for patients with a high frequency of headache
      episodes. PT is most effective for the treatment of migraine when combined with
      other treatments such as thermal biofeedback, relaxation training, and exercise.
      Chiropractic manipulation demonstrated a trend toward benefit in the treatment of
      TTH, but evidence is weak. Chiropractic manipulation is probably more effective
      in the treatment of tension-type headache (TTH) than it is in the treatment of
      migraine. Evidence is lacking regarding the efficacy of these treatments in
      reducing headache frequency, intensity, duration, and disability in many commonly
      encountered clinical situations. Many of the published case series and controlled
      studies are of low quality. CONCLUSIONS AND RECOMMENDATIONS: Further studies of
      improved quality are necessary to more firmly establish the place of physical
      modalities in the treatment of primary headache disorders. With the exception of
      high velocity chiropractic manipulation of the neck, the treatments are unlikely
      to be physically dangerous, although the financial costs and lost treatment
      opportunity by prescribing potentially ineffective treatment may not be
      insignificant. In the absence of clear evidence regarding their role in
      treatment, physicians and patients are advised to make cautious and
      individualized judgments about the utility of physical treatments for headache
      management; in most cases, the use of these modalities should complement rather
      than supplant better-validated forms of therapy.

PMID- 15953307
TI  - Isolated cortical vein thrombosis and the cord sign.

PMID- 15953308
TI  - Bending the rule of monotherapy for migraine prevention?

PMID- 15953309
TI  - The combination of naratriptan and prochlorperazine in migraine treatment.

PMID- 15953310
TI  - Clomiphene citrate as a new treatment for SUNCT: hormonal manipulation for
      hypothalamic-influenced trigeminal autonomic cephalalgias.
AB  - We present a patient with treatment refractory short-lasting unilateral
      neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) who
      was found to have low levels of serum testosterone supporting the hypothalamic
      connection to this trigeminal autonomic cephalalgia. Clomiphene citrate therapy
      induced a significant elevation of testosterone levels (by its effect on
      hypothalamic estrogen receptors) and led to a dramatic reduction in SUNCT
      attacks. Hormonal manipulation may be a treatment strategy for hypothalamic
      influenced trigeminal autonomic cephalalgias.

PMID- 15953311
TI  - Water deprivation: a new migraine precipitant.
AB  - Fifty migraineurs were asked if insufficient fluid intake could provoke their
      migraine attacks. Twenty replied "yes," 7 were doubtfully positive, and 23 said
      "no." In addition 14 of 45 migraineurs at a meeting of the British Migraine
      association (UK) also recognized fluid deprivation as one of their migraine
      triggers. Thus a total of 34 of 95 migraineurs knew that dehydration could
      provoke their attacks, a precipitant not recognized by the medical profession.
      This indicates that we can add fluid deprivation to our list of migraine
      precipitants. It would be interesting to know the extent to which it applies in
      other climates. Further research is needed into the mechanism of this
      precipitant.

PMID- 15953312
TI  - Remitting form of hemicrania continua: two new cases exhibiting one unusual
      autonomic feature.
AB  - Hemicrania continua (HC) is an uncommon, primary headache disorder characterized
      by a continuous, strictly unilateral headache of moderate intensity with
      superimposed exacerbations of more severe pain and accompanying autonomic
      features. Whereas in the majority of HC patients the headache is continuous and
      without pain-free intervals, we report two new cases of the rare remitting form
      of HC. One patient described unusual olfactory sensation during episodes of
      exacerbation, which we classify as an olfactory aura.

PMID- 15953313
TI  - Osmophobia and taste abnormality in migraineurs: a tertiary care study.

PMID- 15953314
TI  - Clinical pearls: can they be of more than anecdotal value?

PMID- 15953319
TI  - Guillain-Barre syndrome in childhood.
AB  - The Guillain-Barre syndrome (GBS) is characterized by the acute onset of rapidly
      progressive, symmetric muscle weakness with absent or decreased muscle stretch
      reflexes. GBS is the most common cause of acute flaccid paralysis in childhood,
      with an incidence in Australia of 0.8 per 100,000 children per year. Recent
      advances in this field have included identification of a number of clinical and
      neurophysiologic subtypes of GBS, enabling improved characterization of etiology
      and improved prognostication in this disorder.

PMID- 15953320
TI  - Tongue-tie.

PMID- 15953321
TI  - Review of tongue-tie release at a tertiary maternity hospital.
AB  - OBJECTIVE: To review the first 12 months of assessment and release of lingual
      frenulum (frenotomy) at a breast-feeding clinic in a tertiary maternity hospital
      (August 2002 to end of July 2003) and to report on the breast-feeding outcomes
      and parental satisfaction. METHODS: A structured telephone interview was
      conducted with the mother at least 3 months after the assessment. Data were
      collected about the presenting problem and the effect of release of the tongue
      tie (if performed). Parents were also asked about their satisfaction with the
      procedure and of problems following the release. RESULTS: Sixty-six babies were
      assessed in 12 months. If infants were assessed as: (i) having impaired lingual
      function (using the Hazelbaker assessment tool for lingual frenulum function);
      (ii) the frenulum visualized to be a thin membrane; and (iii) the parent(s) gave
      informed consent, the frenulum was released. Initial and follow-up data are
      available on 46 infants. Infants had a mean age of 18 days (range 3-98), 63% were
      male infants and most had difficulties with attachment to the breast. Frenotomy
      was performed on 35 infants and breast-feeding improved in 83%. Parents reported
      high levels of satisfaction with the frenotomy procedure and no complications
      were reported. CONCLUSION: Frenotomy is a safe and easy procedure. Infants with a
      significant tongue-tie that is interfering with breast-feeding have shown an
      improvement with breast-feeding following frenotomy.

PMID- 15953322
TI  - Randomized, controlled trial of division of tongue-tie in infants with feeding
      problems.
AB  - OBJECTIVE: To determine whether, in infants with a tongue-tie and a feeding
      problem, the current medical treatment (referral to a lactation consultant) or
      immediate division works best and enables the infants to feed normally. METHODS:
      Between March and July 2002, all the babies in the district of Southampton with
      tongue-ties were followed in order to see if they had any feeding problems. If
      they developed problems, the mothers gave written consent and were enrolled in an
      ethics committee approved, randomized, controlled trial, comparing 48 h of
      intensive lactation consultant support (control) with immediate division.
      RESULTS: A total of 201 babies had tongue-tie, of whom 88 had breast-feeding or
      bottle-feeding problems. Thirty-one were not enrolled, so 57 were randomized. Of
      the 29 controls, one improved (3%) and breast-fed for 8 months, but 28 did not.
      At 48 h, these 28 were offered division, which all accepted, and 27 improved
      (96%) and fed normally. Of the 28 babies who had immediate division, 27 improved
      and fed normally but one remained on a nipple shield (P < 0.001). Twenty-four
      mothers breast-fed for 4 months (24/40, 60%). Overall, division of the tongue-tie
      babies resulted in improved feeding in 54/57 (95%) babies. CONCLUSIONS: This
      randomized, controlled trial has clearly shown that tongue-ties can affect
      feeding and that division is safe, successful and improved feeding for mother and
      baby significantly better than the intensive skilled support of a lactation
      consultant.

PMID- 15953323
TI  - Assessment and follow-up of suspected child abuse in preschool children with
      fractures seen in a general hospital emergency department.
AB  - OBJECTIVE: To evaluate the emergency department assessment and follow-up of
      possible child abuse in children with fractures. METHODS: A retrospective audit
      was conducted of children up to 3 years of age who presented with a fracture to a
      general hospital emergency department over a 2-year period. RESULTS: In the 98
      cases included, there was no documentation of complete physical examination in
      57% of cases, whether the injury was witnessed in 54%, or time of injury in 18%.
      In 27% of cases the history documented was too brief to assess consistency of the
      injury with the history. Seventy-five per cent of children with known prior
      injuries did not have their past history documented. In 80% of all cases there
      was no indication that the emergency department doctor had considered the
      possibility of child abuse. Emergency doctors did not recognize four out of 16
      cases (25%) with inconsistent histories. There was poor follow-up of patients in
      whom abuse was suspected: 46% of children less than 2 years had neither a
      skeletal survey nor bone scan. Patients referred to a paediatrician by the
      emergency department were significantly more likely to have a skeletal survey
      performed and to have the diagnosis of child abuse confirmed. CONCLUSIONS:
      Emergency department staff in a general hospital do not document or assess for
      all of the indicators of child abuse in a high-risk population and they do not
      document consideration of the diagnosis in the majority of cases. Emergency
      department staff need more training and more resources to allow for full
      assessment of child abuse. Suspected child abuse cases should be referred to a
      paediatrician to improve investigation and follow-up.

PMID- 15953324
TI  - Digital imaging does not improve localization of percutaneously inserted central
      lines in neonates.
AB  - OBJECTIVE: To determine whether the use of digital imaging improves the
      localization of percutaneously inserted central (PIC) line tips compared to
      standard radiographs, with contrast being used in both cases. METHODS: Digital
      radiographs taken for localization of PIC lines between October 2002 and
      September 2003 were identified from the neonatal database. Two reporters
      independently reviewed the radiographs and stated (i) whether the tip could
      confidently be seen and (ii) the position. The observers were encouraged to use
      all the image modification modalities available. The formal radiology report was
      taken as the third 'reporter'. RESULTS: Overall 117 digital radiographs from 98
      infants were reviewed. Reporter 1 identified the tip in 83 (71%); reporter 2 in
      84 (72%); and the radiologist in 95 (81%), although all agreed that the tip could
      be identified in only 55 (47%) radiographs. In radiographs where the reporters
      agreed that the tip could be identified, they agreed on the position in 37 (67%)
      cases. In 61 (52%) radiographs the reporters did not agree that the tip could be
      seen, but they agreed on its position in 36 (59%) cases. The kappa coefficient
      for agreement on line position was 0.63. The level of agreement between reporters
      in this study using digital imaging was not significantly different from our
      previous findings using standard radiography with contrast (74/117, 63% vs 57/96,
      59%). CONCLUSION: The use of digital imaging, with its ability to manipulate
      images in order to identify PIC line tips, is not significantly better than using
      standard radiography with contrast.

PMID- 15953325
TI  - Adolescents and sexually transmitted infections: knowledge and behaviour in
      Italy.
AB  - OBJECTIVE: Sexually transmitted infections (STI) among adolescents continue to be
      an important public health problem for many industrialized and developing
      countries. This study evaluated knowledge and behaviour in adolescents regarding
      prevention of STI. METHODS: Information was obtained by using self-reported
      questionnaire from a random sample of 644 undergraduate students at university
      and at public high schools aged 14-20 years in Catanzaro (Italy). RESULTS: Only
      14.2% of respondents knew about the main STI and that they can be transmitted
      through sexual intercourse with HIV seropositive partners; this knowledge was
      significantly higher among adolescents who had had a higher number of sexual
      partners in their lifetime and who had received information from physicians about
      STI. A total of 33.8% reported having had sexual intercourse at least once and
      the mean age at first intercourse was 16 years. Older males and adolescents with
      employed mothers were more likely to have reported having had a sexual
      experience. The prevalence of using condoms every time during sexual intercourse
      was 51.8% and such behaviour was more likely in younger adolescents and males.
      The prevalence of condom use on the last occasion of sex was 71.9%. Younger
      adolescents, those with a higher perception of the risk of contracting STI and
      those with lesser knowledge about STI were independent predictors for using
      condoms. The mean total score of the respondents' perception of a risk of
      contracting STI was 5.8. CONCLUSIONS: Evidence to develop and implement
      strategies with the hope of improving adolescents' level of knowledge and
      reducing unsafe sexual practices.

PMID- 15953326
TI  - Risks of seroconversion of hepatitis B, hepatitis C and human immunodeficiency
      viruses in children with multitransfused thalassaemia major.
AB  - OBJECTIVES: To estimate the risks of seroconversion of hepatitis B virus (HBV),
      hepatitis C virus (HCV) and human immunodeficiency viruses (HIV) in children with
      multitransfused thalassaemia at a thalassaemic clinic in Kuala Lumpur, Malaysia.
      METHODS: Seventy-two children (39 males, median age 11.3 years, 2.5th-97.5th
      centile: 1.4-19.2 years) with thalassaemia major were studied. The risks of
      seroconversion of HBV, HCV and HIV were estimated by comparing the
      seroprevalences of hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV
      between a defined starting point and an end point. The end point was the point
      when latest serological results were available while the starting point was when
      regular transfusion was commenced, or approximately 5 years before the end point
      when the duration of transfusion was longer. RESULTS: The median duration of the
      study was 49 months (range 8-69 months, total 2953 patient-months). There were
      2605 transfusion episodes and 4154 units of blood transfused (0.88 transfusion
      episode/patient per month, 1.41 units of blood transfused/patient per month).
      There were three new seroconversions for anti-HCV but none for HBsAg and anti
      HIV. The risk of seroconversion for HCV was one in 1384 units of blood transfused
      (95% CI: 4000-472). The seroprevalence rates at the starting and end points were:
      HBsAg (1%, 1%), anti-HCV (10%, 13%) and anti-HIV (0%, 0%), respectively.
      CONCLUSIONS: The estimated risk of acquiring HCV infection in children receiving
      multiple blood transfusions in this study is surprisingly higher than the
      generally accepted estimated risk. Other routes of transmission may be important.
      A prospective, multicentre study to estimate such risks more precisely is needed.

PMID- 15953327
TI  - Infective endocarditis: experience of a paediatric emergency department.
AB  - OBJECTIVES: To determine the clinical features at presentation of children with
      infective endocarditis to a tertiary centre and review the role of the emergency
      department in these cases. The subsequent course and outcomes are briefly
      discussed. METHODS: Retrospective audit of children with endocarditis presenting
      to a tertiary children's hospital over a 16-year period. RESULTS: Twenty-three
      cases of infective endocarditis were identified. Initial presentation via the
      paediatric emergency department occurred in 78% of cases and was associated with
      the least delay to commencement of appropriate treatment. The average duration of
      illness at the time of presentation was 6 days. Prior medical care had been
      sought in 65% of the cases, with antibiotics prescribed for an alternate
      diagnosis in 73%. Children with and without cardiac anomalies were equally
      represented. Of the group with normal cardiac anatomy, 45% presented without a
      murmur. Staphylococcus aureus was the most frequent causative organism (43%) and
      accounted for 64% of cases in children with no pre-existing cardiac
      abnormalities. Permanent sequelae were more likely to occur with S. aureus. The
      overall mortality rate was 9%. CONCLUSIONS: Infective endocarditis is a rare
      illness in children and represents a diagnostic challenge. The majority of cases
      will present via the paediatric emergency department with a non-specific febrile
      illness, having frequently commenced antibiotics for an alternate diagnosis.
      Specific expertise in paediatric emergency care can assist in early diagnosis and
      management. Morbidity remains significant, particularly in cases caused by S.
      aureus.

PMID- 15953328
TI  - Acute adenitis in children: clinical course and factors predictive of surgical
      drainage.
AB  - OBJECTIVES: To describe clinical course of children hospitalized for a first
      episode of acute unilateral infectious adenitis and to identify factors
      predictive of surgical lymph node drainage. METHODS: We reviewed medical records
      of children from 0 to 17 years of age discharged from a tertiary care pediatric
      center with a diagnosis of adenitis between 1 April 1996 and 31 March 2001.
      Patients were included if they had acute (< or = 10 days) unilateral lymph node
      swelling greater or equal to 2.5 cm on initial physical examination. Exclusion
      criteria were: bilateral adenitis or adenitis at more than one site; prior
      adenitis; underlying chronic disease. RESULTS: Two hundred and eighty-four
      patients were included in this study. The mean age was 4.0 years (3.1 SD). Twenty
      three per cent of infected nodes were > 5 cm in size and 92.6% were cervical.
      Thirteen of 252 blood cultures were positive (5.2%), of which one showed
      Streptococcus pneumoniae and 12 contaminants. Mean length of stay was 4.2 days
      (2.2 SD). Surgical node drainage was performed in 60 (21.1%) patients. Factors
      significantly associated with increased risk of surgical drainage were age < 1
      year (adjusted OR: 14.5; 95% CI: 5.0-42.2) and node involvement > 48 h (adjusted
      OR: 2.9; 95% CI: 1.2-7.2). There were no major complications. Follow-up was
      documented in 183 patients, of whom 92.3% achieved complete healing. CONCLUSIONS:
      Children hospitalized for a first episode of acute unilateral infectious adenitis
      generally do well. Younger patients and those with longer duration of node
      involvement before admission have an increased risk of surgical node drainage.

PMID- 15953330
TI  - The world's longest surviving paediatric practices: some themes of Aboriginal
      medical ethnobotany in Australia.
AB  - Contemporary paediatric practices of Australian Aboriginal men and women, in more
      than 100 Aboriginal Language Groups, comprise a living discipline whose origins
      predate Western medicine by tens of millennia. The history of paediatrics
      acknowledges this surviving continuum of the world's oldest child-care practices.
      Because of the inextricable nexus between Aboriginal men and women and the land
      in which they live, medical ethnobotany forms a major part of the medical aspects
      of Aboriginal child care. Traditional tribal healers, called 'Nungungi' in some
      language groups of Central Australia, are identified as such whilst still young
      children and are given special education in the healing arts, especially that of
      medical ethnobotany, by older healers. Distinct from this specialized role, all
      Aboriginal men and women (and in particular grandmothers) in traditional
      communities use a sophisticated botanical materia medica in the treatment of sick
      and injured children. In cultures in transition, medical ethnobotanical practices
      may persist long after the local use of flora as sources of traditional food,
      weaponry, totemic identity and religious rites have disappeared. Some selected
      botanical 'cures' were adopted by early European settlers and a number of such
      relict uses have become part of mainstream Western life today, particularly as
      this applies to self-medication. Drugs and medicaments used in the treatment of
      children are obtained from leaves, bark, roots and flowers, usually as fresh
      preparations. They are prepared as infusions, decoctions and macerations and may
      be enjoined with emollients such as emu or kangaroo fat for topical application.
      Botanical drugs and medicaments are usually prepared fresh for each
      administration and are rarely stored. Contemporary Australian ethnobotany
      exploits the medicinal properties of more than 100 genera - using such extracts
      as antiseptics, analgesics, astringents, antipyretics, sedatives, hypnotics,
      expectorants and carminatives. Their widespread use, by the world's oldest
      surviving cultures, reflect perhaps 50 millennia of acute observation and
      clinical interpretation, trial and error, serendipidity and experimentation.
      Australian medical ethnobotany generally, and that used specifically for
      children, is characterized by several features including (i) the multipurpose or
      'broad-spectrum' use of many floral species; (ii) a paradigm of the use of
      botanical material to treat symptoms and symptom-complexes rather than disease
      based treatment; (iii) the widespread and universal medical knowledge of
      botanical remedies by all members of local Aboriginal communities, not only
      traditional community or tribal healers and (iv) the use of botanical material in
      the context of preventive medicine. Seventy per cent of the world's population
      uses traditional herbal remedies in the treatment of sick or injured children. In
      this context, the detailed and extensive ethnobotanical pharmacopoeia of the
      Aboriginal Peoples of Australia holds an important place.

PMID- 15953329
TI  - Long-term outcomes of seriously injured children: a study using the Child Health
      Questionnaire.
AB  - OBJECTIVE: To assess the health-related quality of life (HRQoL) in children 1-2
      years after they had sustained an injury. METHODS: Parents of all children who
      were identified by the Queensland Trauma Registry during their admission to
      either of the two paediatric specialty hospitals in Brisbane, Australia, for the
      treatment of an injury, were invited to participate in this study. Parents who
      consented to participation received a copy of the Child Health Questionnaire
      (CHQ) that required them to provide information regarding their child's HRQoL
      following injury. The CHQ scores for the study respondents were compared with
      those of the Australian norms. This study was approved by the relevant ethics
      committees. RESULTS: Two hundred and forty-one completed questionnaires were
      returned. The majority of cases were male (65%) and there was even representation
      across all age groups. The majority of injuries were considered to be minor (81%)
      and were predominantly the result of falls and cycling accidents causing mainly
      fractures and intracranial injury. On the majority of subscales of the CHQ, study
      participants recorded scores that were statistically significantly below those of
      the Australian norms. None of the relevant variables collected by the Queensland
      Trauma Registry were found to predict scores on the CHQ in this study (for those
      children hospitalized for > 24 h). CONCLUSION: Injured children are worse off
      than their Australian counterparts in terms of HRQoL even up to 2 years following
      an injury. Further research needs to be undertaken to identify factors that
      predict lower HRQoL in order to reduce the burden of injury on children and their
      families.

PMID- 15953331
TI  - Biliary colic: Is it gallstones?

PMID- 15953332
TI  - Coeliac disease presenting as dermatitis herpetiformis in infancy.
AB  - The incidence of reporting and diagnosis of coeliac disease (CD) in children is
      increasing with the improvement in sensitivity and specificity of screening
      markers. This in turn has led to an increasing awareness of gluten-sensitive
      enteropathy and associated disorders. We report the unusual case of an 8-month
      old child presenting to his general practitioner with pruritic skin lesions,
      subsequently proven to be dermatitis herpetiformis (DH) as the first sign of
      gluten-sensitive disease. This infant is the youngest child presenting with DH
      who could be identified from published report dating from 1966 onwards.
      Dermatitis herpetiformis is the commonest associated pathology of CD, although
      rare in infancy, it should be considered in any child presenting with failure to
      thrive and atypical, chronic rash not responding to simple measures.

PMID- 15953333
TI  - Double aortic arch presenting as severe bronchiolitis in a 2-week-old infant.
AB  - A 2-week-old female infant was transferred from a regional hospital for
      mechanical ventilation after developing severe respiratory distress. Stridor had
      been present since the age of 1 week and was complicated by coryzal illness.
      Mechanical ventilation was difficult with marked inspiratory and expiratory flow
      obstruction recorded by the ventilator. Echocardiogram showed a normal heart.
      Flexible bronchoscopy revealed mid-tracheal extrinsic compression (unchanged with
      positive end-expiratory pressure) and advancement of the endotracheal tube by 2
      cm completely corrected the flow obstruction. Repeat echocardiogram showed a
      double aortic arch. This case report emphasizes the importance of clinical
      history, examination findings and interpretation of the ventilator waveforms in
      the differential diagnosis of a difficult-to-ventilate infant with bronchiolitis.

PMID- 15953334
TI  - Severe hyperbilirubinaemia in a Chinese girl with type I Crigler-Najjar syndrome:
      first case ever reported in Mainland China.
AB  - Jaundice is common in ethnic Chinese infants, but to our knowledge Crigler-Najjar
      syndrome (CN syndrome) type I has never been reported in China. A Chinese girl
      with severe jaundice was recently diagnosed to have CN syndrome type I by
      analyzing the bilirubin-uridinediphospho (UDP)-glucuronosyltransferase gene
      (UGT1A1). The patient was homozygous for a nonsense mutation that replaced
      glutamine (CAG, amino acid 239) with stop codon (TAG) at nucleotide number 715
      (715C-->T) in exon 1. No mutation was found in exons 2-5. Her parents were
      heterozygous for the same mutant. The patient had an average bilirubin level of
      300-500 mumol/L and a peak of 701 mumol/L. Daily phototherapy for 15 h was
      required to keep the bilirubin levels within 280-320 mumol/L. The unconjugated
      hyperbilirubinaemia apparently resulted from homozygous nonsense mutation of
      UGT1A1, which could completely abolish the UGT activity towards bilirubin
      (hepatic glucuronidation) and result in CN syndrome type I. Identification of the
      genetic defect is very useful for gene therapy, especially for DNA/RNA chimera
      therapy, and can be used as an antenatal screening test to identify the affected
      offsprings.

PMID- 15953335
TI  - Reye's syndrome developing in an infant on treatment of Kawasaki syndrome.
AB  - Aspirin is commonly used as an anti-inflammatory therapy for Kawasaki syndrome.
      Early initiation with high dose aspirin (80 to > 100 mg/kg per day), followed by
      low-dose therapy at the afebrile stage, has been often used to reduce morbidity
      and mortality in coronary complications. We report a 10-month-old infant who was
      diagnosed with Kawasaki syndrome. Sudden onset of poor activity, poor appetite,
      lethargy, tachycardia, tachypnea, hepatomegaly, increased AST/ALT, coagulopathy
      and hyperammonemia developed 3 days after the high-dose aspirin therapy. His
      histopathological and ultrastructural findings from the liver biopsy were
      compatible with Reye's syndrome. He recovered completely, and there was no
      recurrence.

PMID- 15953336
TI  - An innovative treatment programme for anorexia nervosa.
AB  - We present the case of an Australian girl with severe anorexia nervosa who had
      previously been resistant to treatment, and who was subsequently treated
      successfully by an innovative programme at the Karolinska Institute in Stockholm.
      The programme is based on a distinctive concept of causation of eating disorders
      in which it is postulated that they develop as a consequence of starvation rather
      than a primary mental disorder. The treatment focuses on relearning how to eat
      and perceive satiety using a unique feed-back system, together with provision of
      warmth, limitation of exercise and facilitating social adaptation.

PMID- 15953344
TI  - Monocarboxylate transporters in the central nervous system: distribution,
      regulation and function.
AB  - Monocarboxylate transporters (MCTs) are proton-linked membrane carriers involved
      in the transport of monocarboxylates such as lactate, pyruvate, as well as ketone
      bodies. They belong to a larger family of transporters composed of 14 members in
      mammals based on sequence homologies. MCTs are found in various tissues including
      the brain where three isoforms, MCT1, MCT2 and MCT4, have been described. Each of
      these isoforms exhibits a distinct regional and cellular distribution in rodent
      brain. At the cellular level, MCT1 is expressed by endothelial cells of
      microvessels, by ependymocytes as well as by astrocytes. MCT4 expression appears
      to be specific for astrocytes. By contrast, the predominant neuronal
      monocarboxylate transporter is MCT2. Interestingly, part of MCT2 immunoreactivity
      is located at postsynaptic sites, suggesting a particular role of
      monocarboxylates and their transporters in synaptic transmission. In addition to
      variation in expression during development and upon nutritional modifications,
      new data indicate that MCT expression is regulated at the translational level by
      neurotransmitters. Understanding how transport of monocarboxylates is regulated
      could be of particular importance not only for neuroenergetics but also for areas
      such as functional brain imaging, regulation of food intake and glucose
      homeostasis, or for central nervous system disorders such as ischaemia and
      neurodegenerative diseases.

PMID- 15953345
TI  - Binding of soluble myelin-associated glycoprotein to specific gangliosides
      induces the association of p75NTR to lipid rafts and signal transduction.
AB  - Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth
      from a variety of neurons. Here we show that gangliosides, GT1b and GD1a, as well
      as the Nogo receptor, are functional binding partners for soluble MAG-Fc.
      Postnatal cerebellar neurons from mice deficient in the GalNAcT gene are
      insensitive to MAG with regard to neurite outgrowth and lack in the activation of
      RhoA. MAG-Fc or the antibody to GT1b and GD1a elicits recruitment of p75(NTR.) to
      lipid rafts, specialized microdomain for signal transduction. Disruption of lipid
      rafts results in abolishment of inhibitory effects of MAG-Fc and the Nogo
      peptide. These findings establish gangliosides as functional binding partners for
      soluble MAG. Gangliosides may play a role in translocation of p75(NTR.) to lipid
      rafts for initiation of the signal transduction.

PMID- 15953346
TI  - Distinct mechanisms of neuronal apoptosis are triggered by antagonism of Bcl
      2/Bcl-x(L) versus induction of the BH3-only protein Bim.
AB  - Primary cerebellar granule neurons (CGNs) require depolarizing extracellular
      potassium for their survival. Removal of depolarizing potassium triggers CGN
      apoptosis that requires induction of Bim, a BH3-only Bcl-2 family member. Bim is
      classically thought to promote apoptosis by neutralizing pro-survival Bcl-2
      proteins. To determine if this is the principal function of Bim in CGNs, we
      contrasted Bim-mediated apoptosis to neuronal death induced by HA14-1, a BH3
      domain mimetic that antagonizes Bcl-2 and Bcl-x(L). HA14-1 elicited CGN apoptosis
      characterized by caspase 3 and 9 activation, cytochrome c release, conformational
      activation of Bax, and mitochondrial depolarization. HA14-1 provoked CGN
      apoptosis in the absence of Bim induction and negative regulators of Bim
      transcription did not prevent HA14-1-induced cell death. However, the antioxidant
      glutathione and its precursor, N-acetyl-l-cysteine, suppressed HA14-1-induced
      apoptosis. Similarly, apoptosis induced by either a structurally distinct Bcl
      2/Bcl-x(L) inhibitor (compound 6) or Bcl-2 antisense oligonucleotides was
      diminished by glutathione. In contrast, antioxidants had no effect on CGN
      apoptosis provoked by either removal of depolarizing potassium or overexpression
      of a GFP-Bim fusion protein, two models of Bim-dependent death. These data show
      that antagonism of Bcl-2/Bcl-x(L) function elicits oxidative stress-dependent CGN
      apoptosis that is mechanistically distinct from Bim-mediated cell death. These
      results further indicate that, although Bcl-2/Bcl-x(L) antagonism is sufficient
      to induce neuronal apoptosis, Bim likely promotes neuronal death by interacting
      with additional proteins besides Bcl-2/Bcl-x(L).

PMID- 15953347
TI  - Chronic nicotine exposure alters blood-brain barrier permeability and diminishes
      brain uptake of methyllycaconitine.
AB  - Methyllycaconitine (MLA) is reported to be a selective antagonist for the
      nicotinic acetylcholine receptor alpha7 subtype and has been found in animal
      behavioral studies to reduce nicotine self-administration and attenuate nicotine
      withdrawal symptoms. While MLA crosses the blood-brain barrier (BBB), no studies
      have assessed brain uptake in animals subjected to chronic nicotine exposure.
      Given that chronic nicotine administration has been reported to alter BBB
      parameters that may affect the kinetic BBB passage of MLA, we evaluated MLA brain
      uptake in naive and S-(-)nicotine-exposed rats (4.5 mg/kg/day for 28 days;
      osmotic minipumps) using in situ rat brain perfusions. Our results demonstrate
      that in situ(3)H-MLA brain uptake rates in naive animals approximate to
      intravenous kinetic data (K(in), 3.24 +/- 0.71 x 10(-4) mL/s/g). However, 28-day
      nicotine exposure diminished (3)H-MLA brain uptake by approximately 60% (K(in),
      1.29 +/- 0.4 x 10(-4) mL/s/g). This reduction was not related to nicotine-induced
      (3)H-MLA brain efflux or BBB transport alterations. Similar experiments also
      demonstrated that the passive permeation of (14)C-thiourea was diminished
      approximately 24% after chronic nicotine exposure. Therefore, it appears that
      chronic nicotine exposure diminishes the blood-brain passive diffusion of
      compounds with very low extraction rates (i.e. permeability-limited compounds).
      These findings imply that the pharmacokinetics of neuropharmaceutical agents that
      are permeability limited may need to be re-evaluated in individuals exposed to
      nicotine.

PMID- 15953348
TI  - Differential monoaminergic, neuroendocrine and behavioural responses after
      central administration of corticotropin-releasing factor receptor type 1 and type
      2 agonists.
AB  - Corticotropin-releasing factor (CRF) mediates various aspects of the stress
      response. To differentiate between the roles of CRF(1) and CRF(2) receptor
      subtypes in monoaminergic neurotransmission, hypothalamic-pituitary
      adrenocortical axis activity and behaviour we compared the effects of CRF and
      urocortin 1 with those of the selective CRF(2) receptor ligands urocortin 2 and
      urocortin 3. In vivo microdialysis in the rat hippocampus was used to assess free
      corticosterone, extracellular levels of serotonin (5-HT) and noradrenaline (NA),
      and their metabolites 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4
      hydroxyphenylglycol (MHPG), respectively. Intracerebroventricular (i.c.v.)
      injection of CRF and urocortin 1, 2 and 3 (1.0 microg) increased hippocampal
      levels of 5-HT and 5-HIAA. CRF and urocortin 1 increased NA and MHPG, whereas
      urocortin 2 and urocortin 3 elevated MHPG, but not NA levels. CRF and the
      urocortins induced an immediate increase in behavioural activity. CRF and
      urocortin 1 mainly caused grooming and exploratory behaviour. In contrast,
      urocortin 2 and urocortin 3 both induced exploratory behaviour, but not grooming,
      and increased time spent eating food pellets. All urocortins, but not CRF,
      suppressed food intake 4-6 h after injection. Hippocampal free corticosterone
      levels were elevated by CRF, urocortin 1 and 3, but not by urocortin 2. The time
      courses of the CRF- and urocortin 1-induced responses were significantly
      prolonged as compared to those of the CRF(2) receptor ligands. The stimulatory
      changes evoked by CRF and urocortin 1 were present up to 4-6 h after injection,
      whereas the effects of urocortin 2 and urocortin 3 returned to baseline within
      2.5 h after injection. Pre-treatment with the selective antagonist antisauvagine
      30 (5.0 microg, i.c.v.) confirmed that the effects of urocortin 3 were CRF(2)
      receptor-mediated. The differential time course of the monoaminergic,
      neuroendocrine and behavioural effects of CRF and urocortin 1, as compared to
      urocortin 2 and urocortin 3, and the specific behavioural pattern induced by the
      CRF(2) receptor ligands, suggest a distinct role for CRF(2) receptors in the
      stress response.

PMID- 15953349
TI  - Length and overall sequence of the PEN-2 C-terminal domain determines its
      function in the stabilization of presenilin fragments.
AB  - Gamma-secretase is an aspartyl protease complex that catalyzes the intramembrane
      cleavage of a subset of type I transmembrane proteins including the beta-amyloid
      precursor protein (APP) implicated in Alzheimer's disease. Presenilin (PS),
      nicastrin (NCT), anterior pharynx defective (APH-1) and presenilin enhancer-2
      (PEN-2) constitute the active gamma-secretase complex. PEN-2, the smallest
      subunit, is required for triggering PS endoproteolysis. Stabilization of the
      resultant N- and C-terminal fragments, which carry the catalytically active site
      aspartates, but not endoproteolysis itself, requires the C-terminal domain of PEN
      2. To functionally dissect the C-terminal domain we created C-terminal deletion
      mutants and mutagenized several evolutionary highly conserved residues. The PEN-2
      mutants were then probed for functional complementation of a PEN-2 knockdown,
      which displays deficient PS1 endoproteolysis and impaired NCT maturation.
      Progressive truncation of the C-terminus caused increasing loss of function. This
      was also observed for an internal deletion mutant as well as for C-terminally
      tagged PEN-2 with a twofold elongated C-terminal domain. Interestingly, only
      simultaneous, but not individual substitution of the highly conserved D90, F94,
      P97 and G99 residues with alanine interfered with PEN-2 function. All loss of
      function mutants identified allowed PS1 endoproteolysis, but failed to stably
      associate with the resultant PS1 fragments, which like the PEN-2 loss of function
      mutants underwent proteasomal degradation. However, complex formation of the PEN
      2 mutants with PS1 fragments could be recovered when proteasomal degradation was
      blocked. Taken together, our data suggest that the PS-subunit stabilizing
      function of PEN-2 depends on length and overall sequence of its C-terminal
      domain.

PMID- 15953350
TI  - Dopaminergic transmission in STOP null mice.
AB  - Neuroleptics are thought to exert their anti-psychotic effects by counteracting a
      hyper-dopaminergic transmission. Here, we have examined the dopaminergic status
      of STOP (stable tubule only polypeptide) null mice, which lack a microtubule
      stabilizing protein and which display neuroleptic-sensitive behavioural
      disorders. Dopamine transmission was investigated using both behavioural analysis
      and measurements of dopamine efflux in different conditions. Compared to wild
      type mice in basal conditions or following mild stress, STOP null mice showed a
      hyper-locomotor activity, which was erased by neuroleptic treatment, and an
      increased locomotor reactivity to amphetamine. Such a behavioural profile is
      indicative of an increased dopaminergic transmission. In STOP null mice, the
      basal dopamine concentrations, measured by quantitative microdialysis, were
      normal in both the nucleus accumbens and the striatum. When measured by
      electrochemical techniques, the dopamine efflux evoked by electrical stimulations
      mimicking physiological stimuli was dramatically increased in the nucleus
      accumbens of STOP null mice, apparently due to an increased dopamine release,
      whereas dopaminergic uptake and auto-inhibition mechanisms were normal. In
      contrast, dopamine effluxes were slightly diminished in the striatum. Together
      with previous results, the present study indicates the association in STOP null
      mice of hippocampal hypo-glutamatergy and of limbic hyper-dopaminergy. Such
      neurotransmission defects are thought to be central to mental diseases such as
      schizophrenia.

PMID- 15953351
TI  - Suppression of glial glutamine release to the extracellular fluid studied in vivo
      by NMR and microdialysis in hyperammonemic rat brain.
AB  - Release of glial glutamine (GLN) to the extracellular fluid (ECF), mainly
      mediated by the bidirectional system N transporter SN1, was studied in vivo in
      hyperammonemic rat brain, using (15)N-nuclear magnetic resonance (NMR) to monitor
      intracellular [5-(15)N]GLN and microdialysis/gradient (1)H-(15)N heteronuclear
      single-quantum correlation NMR to analyse extracellular [5-(15)N]GLN. GLN(ECF)
      was elevated to 2.4 +/- 0.2 mm after 4.5 h of intravenous ammonium acetate
      infusion. The [GLN(i)]/[GLN(ECF)] ratio (i = intracellular) was 9.6 +/- 0.9,
      compared with 17-20 in normal brain. GLN(ECF) then decreased substantially at t =
      4.9 +/- 0.1 h. Comparison of the time-courses of intra- and extra-cellular [5
      (15)N]GLN strongly suggested that the observed decrease reflects partial
      suppression of glial GLN release to ECF. Suppression also followed elevation of
      GLN(ECF) to 1.9 mM, resulting in a [GLN](i)/[GLN(ECF)] ratio of 8.4, upon
      perfusion of alpha-(methylamino)isobutyrate which inhibits neuronal uptake of
      GLN(ECF) mediated by sodium-coupled amino acid transporter (SAT). The results
      provide first evidence for bidirectional operation of SN1 in vivo, and clarify
      the effect of transmembrane GLN gradient on glial GLN release at physiological
      Na(+) gradient. Implications of the results for SN1 as an additional regulatory
      site in the glutamine/glutamate cycle and utility of this approach for examining
      the role of GLN in an experimental model of fulminant hepatic failure are
      discussed.

PMID- 15953352
TI  - Constitutive high-affinity choline transporter endocytosis is determined by a
      carboxyl-terminal tail dileucine motif.
AB  - Maintenance of acetylcholine synthesis depends on the effective functioning of a
      high-affinity sodium-dependent choline transporter (CHT1). Recent studies have
      shown that this transporter is predominantly localized inside the cell, unlike
      other neurotransmitter transporters, suggesting that the trafficking of CHT1 to
      and from the plasma membrane may play a crucial role in regulating choline
      uptake. Here we found that CHT1 is rapidly and constitutively internalized in
      clathrin-coated vesicles to Rab5-positive early endosomes. CHT1 internalization
      is controlled by an atypical carboxyl-terminal dileucine-like motif (L531, V532)
      which, upon replacement by alanine residues, blocks CHT1 internalization in both
      human embryonic kidney 293 cells and primary cortical neurons and results in both
      increased CHT1 cell surface expression and choline transport activity.
      Perturbation of clathrin-mediated endocytosis with dynamin-I K44A increases cell
      surface expression and transport activity to a similar extent as mutating the
      dileucine motif, suggesting that we have identified the motif responsible for
      constitutive CHT1 internalization. Based on the observation that the localization
      of CHT1 to the plasma membrane is transient, we propose that acetylcholine
      synthesis may be influenced by processes that lead to the attenuation of
      constitutive CHT1 endocytosis.

PMID- 15953353
TI  - Caspase 7: increased expression and activation after traumatic brain injury in
      rats.
AB  - Caspases, a cysteine proteinase family, are required for the initiation and
      execution phases of apoptosis. It has been suggested that caspase 7, an apoptosis
      executioner implicated in cell death proteolysis, is redundant to the main
      executioner caspase 3 and it is generally believed that it is not present in the
      brain or present in only minute amounts with highly restricted activity. Here we
      report evidence that caspase 7 is up-regulated and activated after traumatic
      brain injury (TBI) in rats. TBI disrupts homeostasis resulting in pathological
      apoptotic activation. After controlled cortical impact TBI of adult male rats we
      observed, by semiquantitative real-time PCR, increased mRNA levels within the
      traumatized cortex and hippocampus peaking in the former about 5 days post-injury
      and in the latter within 6-24 h of trauma. The activation of caspase 7 protein
      after TBI, demonstrated by immunoblot by the increase of the active form of
      caspase 7 peaking 5 days post-injury in the cortex and hippocampus, was found to
      be up-regulated in both neurons and astrocytes by immunohistochemistry. These
      findings, the first to document the up-regulation of caspase 7 in the brain after
      acute brain injury in rats, suggest that caspase 7 activation could contribute to
      neuronal cell death on a scale not previously recognized.

PMID- 15953354
TI  - Regulated expression of endothelial lipase by porcine brain capillary endothelial
      cells constituting the blood-brain barrier.
AB  - Normal neurological function depends on a constant supply of polyunsaturated
      fatty acids to the brain. A considerable proportion of essential fatty acids
      originates from lipoprotein-associated lipids that undergo uptake and/or
      catabolism at the blood-brain barrier (BBB). This study aimed at identifying
      expression and regulation of endothelial lipase (EL) in brain capillary
      endothelial cells (BCEC), major constituents of the BBB. Our results revealed
      that BCEC are capable of EL synthesis and secretion. Overexpression of EL
      resulted in enhanced hydrolysis of extracellular high-density lipoprotein (HDL)
      associated sn-2-labeled [(14)C]20 : 4 phosphatidylcholine. [(14)C]20 : 4 was
      recovered in cellular lipids, indicating re-uptake and intracellular re
      esterification. To investigate local regulation of EL in the cerebrovasculature,
      BCEC were cultured in the presence of peroxisome-proliferator activated receptor
      (PPAR)- and liver X receptor (LXR)-agonists, known to regulate HDL levels. These
      experiments revealed that 24(S)OH-cholesterol (a LXR agonist), bezafibrate (a
      PPARalpha agonist), or pioglitazone (a PPARgamma agonist) resulted in down
      regulation of EL mRNA and protein levels. Our findings implicate that EL could
      generate fatty acids at the BBB for transport to deeper regions of the brain as
      building blocks for membrane phospholipids. In addition PPAR and LXR agonists
      appear to contribute to HDL homeostasis at the BBB by regulating EL expression.

PMID- 15953355
TI  - Subunits of the epithelial sodium channel family are differentially expressed in
      the retina of mice with ocular hypertension.
AB  - Glaucoma is a prevalent cause of blindness, resulting in the apoptotic death of
      retinal ganglion cells and optic nerve degeneration. The disease is often
      associated with elevated intraocular pressure, however, molecular mechanisms
      involved in ganglion cell death are poorly understood. To identify proteins
      contributing to this pathological process, we analysed the retinal gene
      expression of DBA/2J mice that develop an elevated intraocular pressure by the
      age of 6 months with subsequent ganglion cell loss. In this study, we identified
      subunits of the epithelial sodium channel (ENaC) family that are specifically
      expressed under elevated intraocular pressure. Using reverse transcriptase
      polymerase chain reaction we observed a significant increase of alpha-ENaC in the
      neuronal retina of DBA/2J mice when compared with control animals, while beta
      ENaC and gamma-ENaC were not detectable in this tissue. Specific immune sera to
      ENaC subunits showed up-regulation of alpha-ENaC in synaptic and nuclear layers
      of the retina, and in the retinal pigment epithelium. Consistent with our
      polymerase chain reaction data, beta-ENaC was not detected by specific antibodies
      in the retina, while gamma-ENaC was only present in the retinal pigment
      epithelium under ocular hypertension. Finally, the increase of alpha-ENaC gene
      expression in the neuronal retina and the retinal pigment epithelium was not
      observed in other tissues of DBA/2J mice. Since the intraocular pressure is
      regulated by the transport of aqueous humour across epithelial structures of the
      eye that in turn is associated with ion flux, the specific up-regulation of ENaC
      proteins could serve as a protecting mechanism against elevated intraocular
      pressure.

PMID- 15953356
TI  - The tissue-specific methylation of the human tyrosine hydroxylase gene reveals
      new regulatory elements in the first exon.
AB  - The methylation status of CpG dinucleotides located in or near regulatory
      elements affects gene expression. The CpG-rich sequence located outside the 5'
      promoter region of the human Tyrosine Hydroxylase (TH) gene appears to influence
      the functional effect of the adjacent intronic HUMTH01 microsatellite. In order
      to identify new regulatory elements in this region acting on gene expression, the
      methylation profile of the TH CpG island was investigated using the bisulfite
      sequencing method. The overall methylation level of this region is correlated to
      TH-expressing and non-expressing status in cell lines and DNA demethylation
      treatment with 5-azacytidine increased TH expression. Moreover, in a homogeneous
      background of methylated CpGs, a single CpG in the first exon of the gene is
      constantly either unmethylated or methylated in, respectively, TH-expressing or
      non-expressing cell lines, tissues and single cells. Further analysis ascertained
      that this CpG is contained in a sequence characterized by putative binding sites
      for the AP2, Sp1 and KAISO factors. Characterization of this sequence shows that
      these factors specifically bind their respective sites. Finally, the binding of
      KAISO, a transcriptional repressor, is conditioned by the methylation of this
      sequence, which may, thus, participate in the regulation of TH gene expression
      according to its methylation pattern.

PMID- 15953357
TI  - Regionally and functionally distinct serotonin3 receptors control in vivo
      dopamine outflow in the rat nucleus accumbens.
AB  - Central serotonin(3) (5-HT(3)) receptors control the mesoaccumbens dopamine (DA)
      pathway. This control is thought to be conditional and might involve regionally
      distinct subpopulations of 5-HT(3) receptors. Here, using in vivo microdialysis
      in rats, we assessed the relative contribution of nucleus accumbens (Nacc) 5
      HT(3) receptors to the overall influence exerted by 5-HT(3) receptors on accumbal
      DA release induced by different drugs or treatments. In freely moving rats, pre
      treatment with 5-HT(3) antagonists (0.1 mg/kg ondansetron and/or 0.03 mg/kg MDL
      72222, s.c.) reduced DA efflux enhanced by morphine (1-10 mg/kg, s.c.) and
      haloperidol (0.01 mg/kg, s.c.), but not amphetamine (1-2.5 mg/kg, i.p.) or
      cocaine (10-20 mg/kg, i.p.), the latter two drugs do not trigger depolarization
      stimulated DA exocytosis. Intra-Nacc administration of ondansetron (1 microm) in
      freely moving rats reduced the DA effects elicited by 10 mg/kg morphine, but not
      1 mg/kg morphine or haloperidol. The 5-HT(1A) agonist 8-OH-DPAT (0.1 mg/kg,
      s.c.), known to decrease central 5-HT tone, reduced 10 but not 1 mg/kg morphine
      stimulated DA outflow in freely moving rats. In halothane-anaesthetized rats,
      intra-Nacc ondansetron (1 microm) application reduced dorsal raphe nucleus
      electrical stimulation (20Hz)-induced DA outflow. Our results show that
      regionally distinct populations of 5-HT(3) receptors control the depolarization
      dependent exocytosis of DA and suggest that the involvement of Nacc 5-HT(3)
      receptors occurs only when central DA and 5-HT tones are concomitantly increased.

PMID- 15953358
TI  - Opposite effects of Zn on the in vitro binding of [3H]LY354740 to recombinant and
      native metabotropic glutamate 2 and 3 receptors.
AB  - We investigated the effect of Zn on agonist binding to both recombinant and
      native mGlu2 and mGlu3 receptors. Zn had a biphasic inhibitory effect on
      recombinant mGlu2 with IC(50) values for the high- and low-affinity components of
      60 +/- 10 microM and 2 +/- 0.7 mM, respectively. Zn induced a complex biphasic
      effect of inhibition and enhancement of [(3)H]LY354740 binding to mGlu3.
      Observations with a series of chimeric mGlu2/3 receptors suggest that the Zn
      effect resides in the N-terminal domain of mGlu2 and mGlu3. We observed that the
      His56 of mGlu2, which corresponds to Asp63 in mGlu3 was largely accountable for
      the second phase of the Zn effect. As revealed by quantitative receptor
      radioautography, the addition of up to 100 microm Zn to brain sections of wild
      type mice resulted in significant decreases in binding density in most brain
      regions. In particular, the mid-molecular layer of the dentate gyrus (DGmol) and
      the CA1 lacunosum moleculare of hippocampus (CA1-LMol) showed reductions of 62
      and 67%, respectively. In contrast, the addition of 300 microM Zn to brain
      sections of mGlu2(-/-) mice caused large increases in binding density of 289 and
      242% in DGmol and CA1-LMol, respectively. Therefore, Zn might play a role as a
      physiological modulator of group II mGlu receptor function.

PMID- 15953359
TI  - Differential long-term neuroadaptations of glutamate receptors in the basolateral
      and central amygdala after withdrawal from cocaine self-administration in rats.
AB  - Humans and laboratory animals remain highly vulnerable to relapse to cocaine
      seeking after prolonged periods of withdrawal from the drug. It has been
      hypothesized that this persistent cocaine relapse vulnerability involves drug
      induced alterations in glutamatergic synapses within the mesolimbic dopamine
      reward system. Previous studies have shown that cocaine self-administration
      induces long-lasting neuroadaptations in glutamate neurons of the ventral
      tegmental area and nucleus accumbens. Here, we determined the effect of cocaine
      self-administration and subsequent withdrawal on glutamate receptor expression in
      the amygdala, a component of the mesolimbic dopamine system that is involved in
      cocaine seeking and craving induced by drug-associated cues. Rats were trained
      for 10 days to self-administer intravenous cocaine (6 h/day) or saline (a control
      condition) and were killed after one or 30 withdrawal days. Basolateral and
      central amygdala tissues were assayed for protein expression of the alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits (GluR1 and
      GluR2) and the NMDA receptor subunits (NR1, NR2A and NR2B). In the basolateral
      amygdala, GluR1 but not GluR2 levels were increased on days 1 and 30, NR2A levels
      were increased on day 1, and NR2B levels were decreased on day 30 of withdrawal
      from cocaine. In the central amygdala, GluR2 but not GluR1 levels were increased
      on days 1 and 30, NR1 levels were increased on day 30 and NR2A or NR2B levels
      were not altered after withdrawal from cocaine. These results indicate that
      cocaine self-administration and subsequent withdrawal induces long-lasting and
      differential neuroadaptations in basolateral and central amygdala glutamate
      receptors.

PMID- 15953360
TI  - Nuclear translocation of the SRF co-activator MAL in cortical neurons: role of
      RhoA signalling.
AB  - Although it is well established that RhoA signaling pathways play key roles in
      regulating neuronal morphology, their involvement in other aspects of neuronal
      function has received little attention. Recent studies have elucidated a novel
      intracellular signaling pathway used by RhoA to elicit activation of serum
      response factor (SRF)-mediated transcription. In this pathway, activation of RhoA
      triggers nuclear translocation of the SRF co-activator, megakaryocytic acute
      leukemia (MAL). In assessing whether RhoA regulates transcription in neurons via
      this pathway, we have found that a constitutively active form of Tech (transcript
      enriched in cortex and hippocampus), a RhoA guanine nucleotide exchange factor
      (GEF) that is expressed in forebrain neurons, stimulates SRF reporter activity in
      extracts of primary cortical cultures and induces nuclear translocation of MAL in
      cortical neurons. Both of these responses appear to be mediated by Tech's
      activation of RhoA as they are not mimicked by a mutant Tech construct lacking
      RhoA GEF activity and are blocked by C3 transferase, a selective inhibitor of
      RhoA. Furthermore, Tech-induced increases in SRF activity are suppressed by a
      dominant negative MAL construct. These findings demonstrate that RhoA signaling
      pathways are able to regulate transcription in neurons by triggering
      translocation of the SRF co-activator MAL.

PMID- 15953361
TI  - TYRA-2 (F01E11.5): a Caenorhabditis elegans tyramine receptor expressed in the MC
      and NSM pharyngeal neurons.
AB  - Tyramine appears to regulate key processes in nematodes, such as pharyngeal
      pumping, and more complex behaviors, such as foraging. Recently, a Caenorhabditis
      elegans tyramine receptor, SER-2, was identified that is involved in the TA
      dependent regulation of these processes. In the present study, we have identified
      a second C. elegans gene, tyra-2 (F01E11.5) that encodes a tyramine receptor.
      This is the first identification of multiple tyramine receptor genes in any
      invertebrate. Membranes from COS-7 cells expressing TYRA-2 bind [(3)H]tyramine
      with high affinity with a K(d) of 20 +/- 5 nM. Other physiologically relevant
      biogenic amines, such as octopamine and dopamine, inhibit [(3)H]tyramine binding
      with much lower affinity (K(i)s of 1.55 +/- 0.5 and 1.78 +/- 0.6 microM,
      respectively), supporting the identification of TYRA-2 as a tyramine receptor.
      Indeed, tyramine also dramatically increases GTPgammaS binding to membranes from
      cells expressing TYRA-2 (EC(50) of 50 +/- 13 nM) and the TA-dependent GTPgammaS
      binding is PTX-sensitive suggesting that TYRA-2 may couple to Galpha(i/o). Based
      on fluorescence from tyra::gfp fusion constructs, TYRA-2 expression appears to be
      exclusively neuronal in the MC and NSM pharyngeal neurons, the AS family of
      amphid neurons and neurons in the nerve ring, body and tail. Taken together,
      these results suggest that TYRA-2 encodes a second Galpha(i/o)-coupled tyramine
      receptor and suggests that TA-dependent neuromodulation may be mediated by
      multiple receptors and more complex than previously appreciated.

PMID- 15953362
TI  - Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation.
AB  - Inclusions isolated from several neurodegenerative diseases, including
      Alzheimer's disease (AD), are characterized by ubiquitin-positive proteinaceous
      aggregates. Employing confocal and immunoelectron microscopy, we find that the
      ubiquitin-associating protein sequestosome1/p62, co-localizes to aggregates
      isolated from AD but not control brain, along with the E3 ubiquitin ligase,
      TRAF6. This interaction could be recapitulated by co-transfection in HEK293
      cells. Employing both in vitro and in vivo approaches, tau was found to be a
      substrate of the TRAF6, possessing lysine 63 polyubiquitin chains. Moreover, tau
      recovered from brain of TRAF6 knockout mice, compared with wild type, was not
      ubiquitinated. Tau degradation took place through the ubiquitin-proteasome
      pathway and was dependent upon either the K63-polyubiquitin chains or upon p62.
      In brain lysates of p62 knockout mice, tau fails to co-interact with Rpt1, a
      proteasomal subunit, thereby indicating a requirement for p62 shuttling of tau to
      the proteasome. Our results demonstrate that p62 interacts with K63
      polyubiquitinated tau through its UBA domain and serves a novel role in
      regulating tau proteasomal degradation. We propose a model whereby either a
      decline in p62 expression or a decrease in proteasome activity may contribute to
      accumulation of insoluble/aggregated K63-polyubiquitinated tau.

PMID- 15953363
TI  - Inhibition of phosphoinositide 3 kinase-Akt (protein kinase B)-nuclear factor
      kappa B pathway by lovastatin limits endothelial-monocyte cell interaction.
AB  - Integrity of the blood-brain barrier is essential for the normal functioning of
      CNS. Its disruption contributes to the pathobiology of various inflammatory
      neurodegenerative disorders. We have shown that the HMG-CoA reductase inhibitor
      (lovastatin) attenuated experimental autoimmune encephalomyelitis (EAE, an
      inflammatory disease of CNS) in rodents by inhibiting the infiltration of
      mononuclear cells into the CNS. Here, using an in vitro system, we report that
      lovastatin inhibits endothelial-monocyte cell interaction by down-regulating the
      expression of vascular cell adhesion molecule-1 and E-selectin by inhibiting the
      phosphoinositide 3 kinase (PI3-kinase)/protein kinase B (Akt)/nuclear factor
      kappa B (NF-kappaB) pathway in endothelial cells. It inhibits tumor necrosis
      factor alpha (TNFalpha)-induced PI3-kinase, Akt and NF-kappaB activation in these
      cells. Co-transfection of constitutively active forms of PI3-kinase and Akt
      reversed the lovastatin-mediated inhibition of TNFalpha-induced adhesion, as well
      as activation of NF-kappaB, indicating the involvement of the PI3-kinase/Akt
      pathway in the interaction of adhesion molecules and the process of adhesion.
      This study reports that lovastatin down-regulates the pathway affecting the
      expression and interaction of adhesion molecules on endothelial cells, which in
      turn restricts the migration and infiltration of mononuclear cells thereby
      attenuating the pathogenesis of inflammatory diseases.

PMID- 15953364
TI  - mTOR/p70S6k signalling alteration by Abeta exposure as well as in APP-PS1
      transgenic models and in patients with Alzheimer's disease.
AB  - In Alzheimer's disease, neuropathological hallmarks include the accumulation of
      beta-amyloid peptides (Abeta) in senile plaques, phosphorylated tau in
      neurofibrillary tangles and neuronal death. Abeta is the major aetiological agent
      according to the amyloid cascade hypothesis. Translational control includes
      phosphorylation of the kinases mammalian target of rapamycin (mTOR) and p70S6k
      which modulate cell growth, proliferation and autophagy. It is mainly part of an
      anti-apoptotic cellular signalling. In this study, we analysed modifications of
      mTOR/p70S6k signalling in cellular and transgenic models of Alzheimer's disease,
      as well as in lymphocytes of patients and control individuals. Abeta 1-42
      produced a rapid and persistent down-regulation of mTOR/p70S6k phosphorylation in
      murine neuroblastoma cells associated with caspase 3 activation. Using western
      blottings, we found that phosphorylated forms of mTOR and p70S6k are decreased in
      the cortex but not in the cerebellum (devoid of plaques) of double APP/PS1
      transgenic mice compared with control mice. These results were confirmed by
      immunohistochemical methods. Finally, the expression of phosphorylated p70S6k was
      significantly reduced in lymphocytes of Alzheimer's patients, and levels of
      phosphorylated p70S6k were statistically correlated with Mini Mental Status
      Examination (MMSE) scores. Taken together, these findings demonstrate that the
      mainly anti-apoptotic mTOR/p70S6k signalling is altered in cellular and
      transgenic models of Alzheimer's disease and in peripheral cells of patients, and
      could contribute to the pathogenesis of the disease.

PMID- 15953365
TI  - Excitotoxic and apoptotic neuronal death induce different patterns of glial
      activation in vitro.
AB  - We have studied glial activation in rat cerebellar neuronal-glial cultures after
      inducing neuronal death using various stimuli. Cultures were exposed to 100
      microm glutamate for 20 min, which induces excitotoxic neuronal death, or to
      potassium/serum deprivation, which induces apoptosis of granule neurons. We
      evaluated alterations in several parameters related to glial activation: nuclear
      factor-kappaB activation, nitric oxide and tumour necrosis factor-alpha
      production, which are associated with a pro-inflammatory response, glial
      proliferation and phagocytic activity. Although the two experimental models of
      neuronal damage resulted in the death of most neuronal cells within 24 h,
      differences were observed in the response of the various glial parameters
      evaluated. While nitric oxide production was not detected in any case, tumour
      necrosis factor-alpha production, nuclear factor-kappaB activation and glial
      proliferation were only induced in the presence of excitotoxic neuronal death.
      However, phagocytosis was induced in both cases, although earlier in the case of
      apoptotic neuronal death. These results show that glial cells respond to
      excitotoxic neuronal death with an inflammatory response associated with
      proliferation and phagocytosis. In contrast, whilst glial cells do not produce
      pro-inflammatory molecules in the presence of apoptotic neuronal death,
      phagocytic activity is rapidly induced.

PMID- 15953366
TI  - Acute and long-term effects of IL-6 on cultured dorsal root ganglion neurones
      from adult rat.
AB  - IL-6 contributes to pain and hyperalgesia in inflamed tissue. We have
      investigated short- and long-term effects of IL-6 on dorsal root ganglion (DRG)
      neurones. Glycoprotein 130-like immunoreactivity (the signal transduction
      receptor subunit) was found in almost all neurones in DRG sections and in
      cultured DRG neurones from adult rat. In calcium-imaging studies bath application
      of IL-6 caused an increase of intracellular calcium in about one-third of the DRG
      neurones suggesting functional IL-6 receptors in a proportion of neurones. Long
      term but not short-term exposure of DRG neurones to IL-6 in vitro significantly
      enhanced the proportion of DRG neurones expressing neurokinin 1 receptor-like
      immunoreactivity from 10% to up to 40%. This up-regulation was dependent on the
      activation of mitogen-activated protein kinase kinase (MEK) in the neurones,
      suggesting that the mitogen-activated protein kinase (MAPK) pathway is important
      for this effects of IL-6. Calcium-imaging studies demonstrated that previous
      exposure of DRG neurones to IL-6 enhanced the proportion of neurones that exhibit
      a substance P-induced rise in intracellular calcium. These data show that IL-6
      has short- and long-term effects on a proportion of DRG neurones. These effects
      are likely to contribute to pro-nociceptive effects of IL-6.

PMID- 15953367
TI  - Pro-apoptotic activity of N-myc in activation-induced cell death of microglia.
AB  - Brain microglial cells are thought to undergo apoptosis following the exposure to
      inflammatory stimuli such as lipopolysaccharide (LPS) and IFNgamma, which is
      considered as an autoregulatory mechanism to control their own activation state.
      Here, we report that N-myc constitutes a novel apoptotic pathway of LPS/IFNgamma
      activated microglia. The expression of N-myc was synergistically enhanced by LPS
      and IFNgamma in microglia. Tetracycline-based conditional expression of N-myc
      sensitized microglia to nitric oxide (NO)-induced apoptosis. Knockdown of N-myc
      expression using small interfering RNA (siRNA) attenuated LPS/IFNgamma-induced
      microglial apoptosis. An increase in N-myc expression, however, did not affect
      microglial production of NO or TNFalpha. The synergistic effect of LPS/IFNgamma
      on the microglial N-myc induction was mediated through Janus kinase (JAK)/STAT1
      (signal transducer and activator of transcription 1) pathway. Taken together,
      LPS/IFNgamma-induced N-myc participated in the activation-induced cell death of
      microglia by sensitizing the cells to NO-induced apoptosis; however, N-myc did
      not influence the processes of inflammatory activation of microglia.

PMID- 15953368
TI  - Effect of N-acetylaspartylglutamate (NAAG) on non-quantal and spontaneous quantal
      release of acetylcholine at the neuromuscular synapse of rat.
AB  - N-Acetylaspartylglutamate (NAAG), known to be present in rat motor neurons, may
      participate in neuronal modulation of non-quantal secretion of acetylcholine
      (ACh) from motor nerve terminals. Non-quantal release of ACh was estimated by the
      amplitude of the endplate membrane hyperpolarization (H-effect) caused by
      inhibition of nicotinic receptors by (+)-tubocurarine and acetylcholinesterase by
      armin (diethoxy-p-nitrophenyl phosphate). Application of exogenous NAAG decreased
      the H-effect in a dose-dependent manner. The reduction of the H-effect by NAAG
      was completely removed when N-acetyl-beta-aspartylglutamate (betaNAAG) or 2
      (phosphonomethyl)-pentanedioic acid (2-PMPA) was used to inhibit glutamate
      carboxypeptidase II (GCP II), a presynaptic Schwann cell membrane-associated
      ectoenzyme that hydrolyzes NAAG to glutamate and N-acetylaspartate. Bath
      application of glutamate decreased the H-effect similarly to the action of NAAG
      but N-acetylaspartate was without effect. Inhibition of NMDA receptors by dl-2
      amino-5-phosphopentanoic acid, (+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten
      5,10-imine (MK801), and 7-chlorokynurenic acid or inhibition of muscle nitric
      oxide synthase (NO synthase) by N(G)-nitro-l-arginine methyl ester and 3-bromo-7
      nitroindazole completely prevented the decrease of the H-effect by NAAG. These
      results suggest that glutamate, produced by enzymatic hydrolysis of bath-applied
      NAAG, can modulate non-quantal secretion of ACh from the presynaptic terminal of
      the neuromuscular synapse via activation of postsynaptic NMDA receptors and
      synthesis of nitric oxide (NO) in muscle fibers. NAAG also increased the
      frequency of miniature endplate potentials (mEPPs) generated by spontaneous
      quantal secretion of ACh, whereas the mean amplitude and time constants for rise
      time and for decay of mEPPs did not change.

PMID- 15953369
TI  - ALS-IgG-induced selective motor neurone apoptosis in rat mixed primary spinal
      cord cultures.
AB  - There is evidence that in sporadic amyotrophic lateral sclerosis (ALS)
      immunological mechanisms may be involved in the pathophysiology of the disease.
      We tested whether purified IgG from ALS patients induce cell death in rat mixed
      primary spinal cord cultures and compared this with the effect of IgG purified
      from patients with Guillain-Barre syndrome (GBS) or from healthy donors.
      Treatment with ALS-IgG increases caspase-3 apoptosis when compared with control
      IgG or with GBS-IgG, but does not induce death by necrosis. Because ALS is
      characterized by the selective loss of motor neurones, we next assessed the
      differential effect of ALS-IgG on motor neurones or astrocytes. We showed,
      semiquantitatively, that motor neurones are more susceptible to apoptosis when
      cultures were treated with ALS-IgG compared with control-IgG. In conclusion, we
      have demonstrated in primary spinal cord cultures that IgG from patients with ALS
      induces apoptosis selectively in motor neurones, and that the caspase-3 pathway
      is involved. This suggests that immunological mechanisms may contribute to the
      selective loss of motor neurones in ALS.

PMID- 15953370
TI  - Proline mutations induce negative-dosage effects on uptake velocity of the
      dopamine transporter.
AB  - Ala and Gly substitutions for Pro 101 (P101) located in transmembrane domain 2 of
      the dopamine transporter (DAT) abolished transport activity but did not disrupt
      plasma membrane expression. Due to the high conservation of P101 in all
      neurotransmitter transporters and the capability of Pro to add flexibility to
      helices, we hypothesized that P101 contributes to the dynamic feature of
      substrate translocation. To test this hypothesis, here we analysed transport
      activity for DAT mutants where this Pro was mutated into different amino acids,
      including Ser, Val, Leu and Phe. The transmembrane domain 2 helix of P101F,
      unlike the other mutants, was computationally predicted to have a Van der Waals
      energy threefold higher than the wild-type helix. P101F mutant expression was
      consistently disrupted in COS cells. Among all the other mutants that express
      normally, P101V, with a side-chain size close to that of Pro, restores the
      transport activity of P101A by sevenfold. Most importantly, P101V, P101L and
      P101S display negative-dosage effects on dopamine (DA) transport, i.e. the
      velocity-concentration curve for DA uptake does not show a plateau with
      increasing [DA] but rather peaks and then goes down. These data support the view
      that P101 of DAT plays an essential role in DA translocation.

PMID- 15953371
TI  - Transforming growth factor-beta and malignant melanoma: molecular mechanisms.
AB  - Transforming growth factor family members (TGF-beta) are secretory polypeptides
      that have dual tumor-suppressor and oncogenic effects. They signal through kinase
      receptor complexes on the cell surface, which phosphorylate cytoplasmic mediators
      (SMADs). Upon phosphorylation, SMADs march to the nucleus and interact with
      coactivators or corepressors to mediate the transcriptional regulation of several
      genes resulting in diverse effects. In tumorigenesis, malignant cells escape from
      the tumor-suppressive effects of TGF-beta by mutational inactivation or
      dysregulated expression of the molecular components in TGF-beta signaling
      pathway. Although melanoma cells are resistant to the tumor-suppressive effects
      of TGF-beta, there are no detectable defects at the receptor/SMAD level.
      Therefore, in these lesions, it is possible that TGF-beta effects occur
      independently of TGF-beta receptor/SMAD pathway. This review seeks to examine the
      present knowledge about TGF-beta receptor/SMAD signaling pathway and its related
      genes (SMADs, SKI, Filamin, endoglin, Follistatin, and other molecules) in
      melanomas.

PMID- 15953372
TI  - Lupus erythematosus panniculitis (lupus profundus): clinical, histopathological,
      and molecular analysis of nine cases.
AB  - BACKGROUND: The diagnosis of lupus erythematosus panniculitis (LEP) may be very
      difficult in cases in which involvement of the subcutaneous fat is the only
      manifestation of the disease. The main differential diagnosis is subcutaneous
      panniculitis-like T-cell lymphoma (SPTCL). METHODS: We performed a retrospective
      study reviewing the histopathologic features of 11 biopsy specimens from nine
      patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20-71 years).
      RESULTS: Histopathologically, all biopsies revealed a lobular panniculitis, with
      concomitant septal involvement in 82% of them. Dermal changes included the
      presence of superficial and deep infiltrates (82%) and mucin deposition (73%).
      The majority of cases (73%) presented also some form of epidermal involvement.
      The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed
      with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal
      centers were detected in 45% of cases. Immunohistochemistry showed a predominance
      of alpha/beta-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B
      lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)
      gamma gene showed a polyclonal smear in all cases. CONCLUSIONS: Our study shows
      that the most useful histopathologic criteria for distinguishing LEP from SPTCL
      are the presence of involvement of the epidermis, lymphoid follicles with
      reactive germinal centers, mixed cell infiltrate with prominent plasma cells,
      clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.

PMID- 15953373
TI  - Histologic similarities between lentigo maligna and dysplastic nevus: importance
      of clinicopathologic distinction.
AB  - BACKGROUND: Lentigo maligna (LM) can histologically simulate dysplastic nevus
      (DN). Partial biopsy of LM may lead to misdiagnosis. METHODS: One hundred and
      fourteen cases of LM and LM melanoma (LMM) were diagnosed at the Veterans Affairs
      Palo Alto Health Care System (1993-2002). Biopsy and excision specimens for 68 in
      situ and 28 invasive melanomas were classified as having predominant classical LM
      features, predominant DN-like morphology, or a mixed pattern. RESULTS: Biopsy
      specimens demonstrated a predominant classical pattern in 38% (25/65) LM and 36%
      (10/28) LMM, predominant DN-like features in 43% (28/65) LM and 25% (7/28) LMM,
      and mixed pattern in 15% (10/65) LM and 29% (8/28) LMM. Most LM and LMM biopsies
      were partial. Significant DN-like features were present in 51% LM and 57% LMM
      excision specimens. Median age was 72 years for LM and 73 years for LMM, mean
      lesion diameters were 1.3 and 1.7 cm for LM and LMM, respectively, and 85% of LM
      and 75% of LMM cases were located on heavily sun-exposed sites. CONCLUSIONS:
      Misdiagnosis of LM or LMM as DN could have devastating results. Large pigmented
      lesions on sun-damaged skin in elderly individuals should warrant consideration
      of LM/LMM diagnosis, even in the setting of DN-like features histologically.
      Excisional biopsy may help to avoid misdiagnosis.

PMID- 15953374
TI  - Cellular digital fibromas: distinctive CD34-positive lesions that may mimic
      dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Digital fibromas are common benign acral tumors typically reported as
      angiofibromas (AFs) or acquired digital fibrokeratomas (ADFs). Cellular variants
      are not well recognized. METHODS: We collected 14 acral fibrocytic lesions
      showing a spindle cell morphology from our files, and evaluated CD34, Factor
      XIIIa, epithelial membrane antigen (EMA), and S100 protein staining of these
      lesions. We compared the histologic and immunohistochemical features of these
      cellular fibromas with five digital AFs, five ADFs, and five digital
      dermatofibromas. RESULTS: The 14 cellular digital fibromas showed intersecting
      fascicles of thin delicate bland spindle cells in the superficial reticular
      dermis with a fibrotic-to-slight myxoid stroma. The spindle cells in all cases
      stained strongly for CD34, and only scattered stromal cells stained for Factor
      XIIIa. Five tested cases were negative for EMA and S100 protein. The digital AFs,
      fibrokeratomas, and dermatofibromas stained predominately for Factor XIIIa, with
      no or minimal staining for CD34. CONCLUSIONS: These findings suggest that a
      subset of digital fibromas is characterized by a dense cellular proliferation of
      CD34-positive spindle cells. Awareness of this variant of digital fibroma and its
      staining pattern is critical in preventing misdiagnosis as dermatofibrosarcoma
      protuberans, particularly in superficial biopsies.

PMID- 15953375
TI  - Lymphoepithelioma-like carcinoma of the skin with spindle cell differentiation.
AB  - BACKGROUND: Primary cutaneous LELC is a cutaneous neoplasm with histopathologic
      features identical to those seen in the undifferentiated subtype of
      nasopharyngeal carcinoma. It is extremely rare, with only approximately 30 cases
      reported in the literature. METHODS: We report a case of primary cutaneous LELC
      arising on the forehead of a 72 year-old male in which a proportion of the
      neoplastic cells demonstrated distinctive spindle cell morphology. RESULTS:
      Microscopic examination showed a dense lymphoplasmacytic infiltrate admixed with
      large spindle-shaped cells with vesicular nuclei, prominent nucleoli, and
      frequent mitotic figures. These cells were negative for an extensive panel of
      immunohistochemical markers and positive only for broad-spectrum cytokeratins and
      epithelial membrane antigen. There was no connection between the tumor and the
      epidermis and no epidermal dysplasia. In situ hybridization for Epstein-Barr
      virus was negative. CONCLUSIONS: The spindle cell differentiation in this case is
      unusual and suggests that in some cases the differential diagnosis of cutaneous
      spindle cell neoplasms might include primary cutaneous LELC.

PMID- 15953376
TI  - Histologic variants of fibrous papule.
AB  - Fibrous papules (FPs) are common benign lesions usually of the face. Most are
      readily recognizable histologically, although several variants exist that may not
      be as easily diagnosed. These include hypercellular, clear cell, pigmented,
      pleomorphic, and inflammatory variants. A granular cell variant has also been
      described. We microscopically evaluated 212 FPs, and of those, 184 demonstrated
      features of one of the variants. We conclude that variants of FP may be
      encountered not uncommonly. Dermatopathologists should be aware of these to avoid
      misdiagnosis.

PMID- 15953377
TI  - Acroangiodermatitis (pseudo-Kaposi sarcoma) associated with verrucous hyperplasia
      induced by suction-socket lower limb prosthesis.
AB  - Increasing use of suction-socket lower limb prostheses has been associated with
      an increased frequency of dermatological manifestations, linked to the fact that
      the skin of the amputation stump must adapt to an entirely new environment. In
      particular, verrucous hyperplasia and rare cases of acroangiodermatitis (pseudo
      Kaposi sarcoma) have been described. We report a case of amputation stump
      dermatitis, clinically resembling verrucous hyperplasia, but with predominant
      histological aspects of acroangiodermatitis in a patient with a suction-socket
      lower limb prosthesis.

PMID- 15953378
TI  - Hypertext atlas of dermatopathology with expert system for epithelial tumors of
      the skin.
AB  - BACKGROUND: Image resolution required for reference histological images is high.
      Obtaining high-resolution images requires a system, composing large image from
      individual smaller components. Such systems must thus be capable of automatically
      taking individual image parts, performing shading compensation and fusion of the
      image parts into one large image. Distribution of such images over the Internet
      requires developing a suitable user's interface with access to the image details.
      METHODS: The ways of creating high-resolution images (virtual slides) and the
      interface enabling access to image details using Internet browser are described.
      RESULTS: A collection of about 3200 dermatopathological, mostly histologic images
      is available at http://www.muni.cz/atlases: Hypertext atlas of dermatopathology.
      Methods of high-resolution image acquisition were used in digitizing the
      collection of skin lymphomas (Dermatology Institute, University Hospital,
      Zurich), which is a part of the atlas. The atlas is continuously maintained and
      upgraded; the number of contributors is growing.

PMID- 15953379
TI  - Juvenile hyaline fibromatosis: a case report.
AB  - Juvenile hyaline fibromatosis ( JHF ) is a rare autosomal recessive disease
      characterized by papulonodular skin lesions, gingival hyperplasia, joint
      contractures, and bone lesions. The skin lesions may consist of multiple large
      tumors, commonly on the scalp and around the neck, and small pearly, pink papules
      and plaques on the trunk, chin, ears, and around the nostrils. Here, we report a
      2-year-old boy with characteristic stiffness of the knees and elbows and pink
      confluent papules on the paranasal folds, and periauricular and perianal regions.
      He also had hard nodules all over the scalp and around the mouth, and severe
      gingival hyperplasia. The lesions were totally excised and clinicopathological
      diagnosis was JHF.

PMID- 15953380
TI  - Clear cell 'sugar' tumor (PEComa) of the skin: a case report.
AB  - The so-called perivascular epithelioid cell neoplasm (PEComa) family includes
      angiomyolipoma, clear cell 'sugar' tumor (CCST), lymphangioleiomyomatosis, and
      clear cell myomelanocytic tumor (CCMMT). These rare tumors are characterized by
      the co-expression of melanocytic and muscle markers. They have been recognized in
      an increasing number of sites but currently only one case of PEComa, of the CCMMT
      subtype, has been reported in the skin in abstract form. We provide the
      clinicopathologic description of a case of extrapulmonary CCST located in the
      dermis and superficial subcutis of the thigh of a 60-year-old female. The lesion
      was composed of nests of epithelioid and spindle cells with abundant clear to
      granular cytoplasm and distinct cell borders. The tumor showed strong and diffuse
      immunoreactivity with HMB-45. Scattered cells expressed desmin and h-caldesmon.
      Antibodies to S-100 protein, melan-A, cytokeratins, and smooth muscle actin were
      negative. This first case of cutaneous PEComa of the CCST type expands the
      differential diagnosis of clear cell/granular cell tumors of the skin.

PMID- 15953381
TI  - Basal cell carcinoma with matrical differentiation in a transplant patient: a
      case report and review of the literature.
AB  - BACKGROUND: Shadow cells, characterized by basaloid squamous cells with a
      distinct well-defined border and a central unstained area as a shadow of lost
      nuclei, are characteristic of pilomatricoma, a distinct neoplasm of hair matrix
      differentiation. The presence of shadow cells within tumor islands composed of
      follicular germinative cells of an otherwise classic basal cell carcinoma (BCC)
      has been considered as a distinct diagnostic category of BCC with matrical
      differentiation. We present a case of BCC with matrical differentiation in a
      transplant patient. To our knowledge, only 10 cases [Aloi et al. Am J
      Dermatopathol 1988; 10: 509; Ambrojo et al. Am J Dermatopathol 1992; 14: 293;
      Sagol et al. East J Med 1999; 4: 37; Kwittken J. Cutis 2002; 69: 57; Kim et al.
      Yonsei Med J 2003; 44: 523] of BCC showing matrical differentiation have been
      reported. None have been reported arising on the background of immunosuppression.
      METHODS: A 58-year-old male cardiac transplant patient with a nodule on the
      dorsum of left hand was studied. It arose and enlarged rapidly within a few
      months, causing irritation and bleeding. The nodule was surgically excised and
      submitted for histopathologic evaluation. The sections were prepared by
      hematoxylin and eosin (H&E) method. RESULTS: The H&E-stained sections of the hand
      lesion revealed multiple nodular masses of basaloid follicular germinative cells.
      In some areas, there was peripheral palisading and stromal retraction artifact
      typical of classic BCC. In these areas, the tumor nodules were connected to the
      epidermis, whereas in others, it extended deep into the reticular dermis to the
      subcutaneous fat junction. Elsewhere, the majority of the tumor contained a
      population of shadow cells, similar to those in pilomatricoma, with basaloid
      appearing matrical cells in the periphery. Trichohyaline granules were identified
      in the cytoplasm of many of the peripheral basaloid cells. These granules are one
      of the characteristic features of follicular matrix differentiation. Mitoses were
      rare. Areas of cystic degeneration were present throughout the tumor. There was
      no evidence of an infiltrating growth pattern, lymphovascular invasion, or
      sarcomatoid growth pattern. CONCLUSION: BCC with matrical differentiation is a
      distinct pathologic entity and a rare subtype of BCC featuring shadow and
      matrical cells, typically seen in pilomatricoma, a benign hair matrix neoplasm.
      This tumor has not yet been reported in an immunosuppressed transplant patient.

PMID- 15953382
TI  - Solitary glomeruloid haemangioma without POEMS syndrome.
AB  - BACKGROUND: The term 'glomeruloid haemangioma' was coined by Chan et al. for a
      histologically distinctive cutaneous haemangioma, which they considered a
      specific cutaneous marker for POEMS syndrome. Glomeruloid haemangiomas appear to
      be specific to POEMS syndrome, because they have not been reported in patients
      without this syndrome. METHODS: We report on an 86-year-old man without POEMS
      syndrome and with a solitary red papule on the face. RESULTS: A cutaneous biopsy
      showed histological findings consistent with a glomeruloid haemangioma. Physical
      examination of the skin did not show any other cutaneous lesion and laboratory
      and radiological studies ruled out the presence of POEMS syndrome. CONCLUSIONS:
      Glomeruloid haemangiomas could exceptionally be present as solitary vascular
      tumours and out of the context of POEMS syndrome. To our knowledge, this is the
      first case reported of glomeruloid haemangioma without POEMS syndrome. Moreover,
      the presentation on the face is also highly unusual.

PMID- 15953384
TI  - Dopamine, uncertainty and TD learning.
AB  - Substantial evidence suggests that the phasic activities of dopaminergic neurons
      in the primate midbrain represent a temporal difference (TD) error in predictions
      of future reward, with increases above and decreases below baseline consequent on
      positive and negative prediction errors, respectively. However, dopamine cells
      have very low baseline activity, which implies that the representation of these
      two sorts of error is asymmetric. We explore the implications of this seemingly
      innocuous asymmetry for the interpretation of dopaminergic firing patterns in
      experiments with probabilistic rewards which bring about persistent prediction
      errors. In particular, we show that when averaging the non-stationary prediction
      errors across trials, a ramping in the activity of the dopamine neurons should be
      apparent, whose magnitude is dependent on the learning rate. This exact
      phenomenon was observed in a recent experiment, though being interpreted there in
      antipodal terms as a within-trial encoding of uncertainty.

PMID- 15953386
TI  - Genetic loci for ventricular dilatation in the LEW/Jms rat with fetal-onset
      hydrocephalus are influenced by gender and genetic background.
AB  - BACKGROUND: The LEW/Jms rat strain has inherited hydrocephalus, with more males
      affected than females and an overall expression rate of 28%. This study aimed to
      determine chromosomal positions for genetic loci causing the hydrocephalus.
      METHODS: An F1 backcross was made to the parental LEW/Jms strain from a cross
      with non-hydrocephalic Fischer 344 rats. BC1 rats were generated for two specific
      crosses: the first with a male LEW/Jms rat as parent and grandparent, [(F x L) x
      L], designated B group, and the second with a female LEW/Jms rat as the parent
      and grandparent [L x (L x F)], designated C group. All hydrocephalic and a
      similar number of non-hydrocephalic rats from these two groups were genotyped
      with microsatellite markers and the data was analyzed separately for each sex by
      MAPMAKER. RESULTS: The frequency of hydrocephalus was not significantly different
      between the two groups (18.2 and 19.9 %), but there was a significant excess of
      males in the B group. The mean severity of hydrocephalus, measured as the
      ventricle-to-brain width ratio, was ranked as B group < C group < LEW/Jms. For
      the both rat groups, there were several chromosomes that showed possible regions
      with association between phenotype and genotype significant at the 5% or 1.0%
      level, but none of these had significant LOD scores. For the C group with a
      female LEW/Jms parent, there was a fully significant locus on Chr2 with a LOD
      score of 3.81 that was associated almost exclusively with male rats. Both groups
      showed possible linkage on Chr17 and the data combined produced a LOD score of
      2.71, between suggestive and full significance. This locus was largely associated
      with male rats with a LEW/Jms male parent. CONCLUSION: Phenotypic expression of
      hydrocephalus in Lew/Jms, although not X-linked, has a strong male bias. One, and
      possibly two chromosomal regions are associated with the hydrocephalus.

PMID- 15953387
TI  - Legal liabilities in research: early lessons from North America.
AB  - The legal risks associated with health research involving human subjects have
      been highlighted recently by a number of lawsuits launched against those involved
      in conducting and evaluating the research. Some of these cases have been fully
      addressed by the legal system, resulting in judgments that provide some guidance.
      The vast majority of cases have either settled before going to trial, or have not
      yet been addressed by the courts, leaving us to wonder what might have been and
      what guidance future cases may bring. What is striking about the lawsuits that
      have been commenced is the broad range of individuals/institutions that are named
      as defendants and the broad range of allegations that are made. The research
      community should take this early experience as a warning and should reflect
      carefully on practices where research involving human subjects is concerned.

PMID- 15953388
TI  - A draft framework for measuring progress towards the development of a National
      Health Information Infrastructure.
AB  - BACKGROUND: American public policy makers recently established the goal of
      providing the majority of Americans with electronic health records by 2014. This
      will require a National Health Information Infrastructure (NHII) that is far more
      complete than the one that is currently in its formative stage of development. We
      describe a conceptual framework to help measure progress toward that goal.
      DISCUSSION: The NHII comprises a set of clusters, such as Regional Health
      Information Organizations (RHIOs), which, in turn, are composed of smaller
      clusters and nodes such as private physician practices, individual hospitals, and
      large academic medical centers. We assess progress in terms of the availability
      and use of information and communications technology and the resulting
      effectiveness of these implementations. These three attributes can be studied in
      a phased approach because the system must be available before it can be used, and
      it must be used to have an effect. As the NHII expands, it can become a tool for
      evaluating itself. SUMMARY: The NHII has the potential to transform health care
      in America--improving health care quality, reducing health care costs, preventing
      medical errors, improving administrative efficiencies, reducing paperwork, and
      increasing access to affordable health care. While the President has set an
      ambitious goal of assuring that most Americans have electronic health records
      within the next 10 years, a significant question remains "How will we know if we
      are making progress toward that goal?" Using the definitions for "nodes" and
      "clusters" developed in this article along with the resulting measurement
      framework, we believe that we can begin a discussion that will enable us to
      define and then begin making the kinds of measurements necessary to answer this
      important question.

PMID- 15953389
TI  - Visualization-based discovery and analysis of genomic aberrations in microarray
      data.
AB  - BACKGROUND: Chromosomal copy number changes (aneuploidies) play a key role in
      cancer progression and molecular evolution. These copy number changes can be
      studied using microarray-based comparative genomic hybridization (array CGH) or
      gene expression microarrays. However, accurate identification of amplified or
      deleted regions requires a combination of visual and computational analysis of
      these microarray data. RESULTS: We have developed ChARMView, a visualization and
      analysis system for guided discovery of chromosomal abnormalities from microarray
      data. Our system facilitates manual or automated discovery of aneuploidies
      through dynamic visualization and integrated statistical analysis. ChARMView can
      be used with array CGH and gene expression microarray data, and multiple
      experiments can be viewed and analyzed simultaneously. CONCLUSION: ChARMView is
      an effective and accurate visualization and analysis system for recognizing even
      small aneuploidies or subtle expression biases, identifying recurring aberrations
      in sets of experiments, and pinpointing functionally relevant copy number
      changes. ChARMView is freely available under the GNU GPL at
      http://function.princeton.edu/ChARMView.

PMID- 15953390
TI  - Delayed polarization of mononuclear phagocyte transcriptional program by type I
      interferon isoforms.
AB  - BACKGROUND: Interferon (IFN)-alpha is considered a key modulator of
      immunopathological processes through a signature-specific activation of
      mononuclear phagocytes (MPs). This study utilized global transcript analysis to
      characterize the effects of the entire type I IFN family in comparison to a broad
      panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS)
      stimulation in vitro. RESULTS: Immature peripheral blood CD14+ MPs were
      stimulated with LPS and 1 hour later with 42 separate soluble factors including
      cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression
      profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four
      hours after stimulation, the transcriptional analysis of MPs revealed two main
      classes of cytokines: one associated with the alternative and the other with the
      classical pathway of MP activation without a clear polarization of type I IFNs
      effects. In contrast, after 9 hours of stimulation most type I IFN isoforms
      induced a characteristic and unique transcriptional pattern separate from other
      cytokines. These "signature" IFNs included; IFN-beta, IFN-alpha2b/alpha2, IFN
      alphaI, IFN-alpha2, IFN-alphaC, IFN-alphaJ1, IFN-alphaH2, and INF-alpha4B and
      induced the over-expression of 44 genes, all of which had known functional
      relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon
      induced hepatitis C-associated microtubular aggregation protein. A second group
      of type I IFNs segregated separately and in closer association with the type II
      IFN-gamma. The phylogenetic relationship of amino acid sequences among type I
      IFNs did not explain their sub-classification, although differences at positions
      94 through 109 and 175 through 189 were present between the signature and other
      IFNs. CONCLUSION: Seven IFN-alpha isoforms and IFN-beta participate in the late
      phase polarization of MPs conditioned by LPS. This information broadens the
      previous view of the central role played by IFN-alpha in autoimmunity and tumor
      rejection by including and/or excluding an array of related factors likely to be
      heterogeneously expressed by distinct sub-populations of individuals in sickness
      or in response to biological therapy.

PMID- 15953391
TI  - Exploring hepatic hormone actions using a compilation of gene expression
      profiles.
AB  - BACKGROUND: Microarray analysis is attractive within the field of endocrine
      research because regulation of gene expression is a key mechanism whereby
      hormones exert their actions. Knowledge discovery and testing of hypothesis based
      on information-rich expression profiles promise to accelerate discovery of
      physiologically relevant hormonal mechanisms of action. However, most studies so
      far concentrate on the analysis of actions of single hormones and few examples
      exist that attempt to use compilation of different hormone-regulated expression
      profiles to gain insight into how hormone act to regulate tissue physiology. This
      report illustrates how a meta-analysis of multiple transcript profiles obtained
      from a single tissue, the liver, can be used to evaluate relevant hypothesis and
      discover novel mechanisms of hormonal action. We have evaluated the differential
      effects of Growth Hormone (GH) and estrogen in the regulation of hepatic gender
      differentiated gene expression as well as the involvement of sterol regulatory
      element-binding proteins (SREBPs) in the hepatic actions of GH and thyroid
      hormone. RESULTS: Little similarity exists between liver transcript profiles
      regulated by 17-alpha-ethinylestradiol and those induced by the continuos
      infusion of bGH. On the other hand, strong correlations were found between both
      profiles and the female enriched transcript profile. Therefore, estrogens have
      feminizing effects in male rat liver which are different from those induced by
      GH. The similarity between bGH and T3 were limited to a small group of genes,
      most of which are involved in lipogenesis. An in silico promoter analysis of
      genes rapidly regulated by thyroid hormone predicted the activation of SREBPs by
      short-term treatment in vivo. It was further demonstrated that proteolytic
      processing of SREBP1 in the endoplasmic reticulum might contribute to the rapid
      actions of T3 on these genes. CONCLUSION: This report illustrates how a meta
      analysis of multiple transcript profiles can be used to link knowledge concerning
      endocrine physiology to hormonally induced changes in gene expression. We
      conclude that both GH and estrogen are important determinants of gender-related
      differences in hepatic gene expression. Rapid hepatic thyroid hormone effects
      affect genes involved in lipogenesis possibly through the induction of SREBP1
      proteolytic processing.

PMID- 15953392
TI  - Overlay of conventional angiographic and en-face OCT images enhances their
      interpretation.
AB  - BACKGROUND: Combining characteristic morphological and functional information in
      one image increases pathophysiologic understanding as well as diagnostic accuracy
      in most clinical settings. En-face optical coherence tomography (OCT) provides a
      high resolution, transversal OCT image of the macular area combined with a
      confocal image of the same area (OCT C-scans). Creating an overlay image of a
      conventional angiographic image onto an OCT image, using the confocal part to
      facilitate transformation, combines structural and functional information of the
      retinal area of interest. This paper describes the construction of such overlay
      images and their aid in improving the interpretation of OCT C-scans. METHODS: In
      various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope
      (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre,
      Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were
      performed. ImagePro, with a custom made plug-in, was used to make an overlay
      image. The confocal part of the OCT C-scan was used to spatially transform the FA
      image onto the OCT C-scan, using the vascular arcades as a reference. To
      facilitate visualization the transformed angiographic image and the OCT C-scan
      were combined in an RGB image. RESULTS: The confocal part of the OCT C-scan could
      easily be fused with angiographic images. Overlay showed a direct correspondence
      between retinal thickening and FA leakage in Birdshot retinochoroiditis,
      localized the subretinal neovascular membrane and correlated anatomic and
      vascular leakage features in myopia, and showed the extent of retinal and pigment
      epithelial detachment in retinal angiomatous proliferation as FA leakage was
      subject to blocked fluorescence. The overlay mode provided additional insight not
      readily available in either mode alone. CONCLUSION: Combining conventional
      angiographic images and en-face OCT C-scans assists in the interpretation of both
      imaging modalities. By combining the physiopathological information in the
      angiograms with the structural information in the OCT scan, zones of leakage can
      be correlated to structural changes in the retina or pigment epithelium. This
      strategy could be used in the evaluation and monitoring of patients with complex
      central macular pathology.

PMID- 15953393
TI  - Teaching: the role of active manipulation of three-dimensional scatter plots in
      understanding the concept of confounding.
AB  - In teaching epidemiology, confounding is a difficult topic. The authors designed
      active learning objects (LO) based on manipulable three-dimensional (3D) plots to
      facilitate understanding of confounding. The 3D LOs help illustrate of how
      confounding can occur, how it generates bias and how to adjust for it. For the
      development of the LOs, guidelines were formulated based on epidemiology and
      theories of instructional design. These included integrating the conceptual and
      empirical aspects: the causal relationships believed to be operating in the study
      population (conceptual aspect) and data-oriented associations (empirical aspect).
      Other guidelines based on theories of instructional design included: actively
      engage the students, use visual methods when possible, and motivate the students
      about the importance of the topic. Students gave the method strong positive
      evaluations. Experts in epidemiology agreed that the 3D LOs apply generally
      accepted scientific views on confounding. Based on their experiences, the authors
      think that the 3D plots can be useful addition in the teaching of confounding.
      The article includes links and a downloadable file that provide a demonstration
      of the 3D LO-based teaching materials.

PMID- 15953394
TI  - Variations in societal characteristics of spatial disease clusters: examples of
      colon, lung and breast cancer in Japan.
AB  - BACKGROUND: Spatial analyses and ecological studies are essential for
      epidemiology and public health. The present study combining these two methods was
      performed to identify spatial clusters of selected types of cancer in Japan and
      to determine their societal characteristics focusing on homogeneity among
      clusters. RESULTS: Spatial clusters of high mortality rates of male colon and
      lung cancer and of female breast cancer were identified by the spatial scan
      statistic using Japanese municipal data (N = 3360) from 1993 to 1998 and also
      municipalities were divided into four societal clusters based on socioeconomic
      indicators and population density (urban-rich, suburban, rural-poor, and
      clutter). Five, seven, and four mortality clusters were identified for lung,
      colon and breast cancer, respectively. For colon and breast cancer, most
      municipalities of all except one cluster were included in a single societal
      cluster (urban-rich). The municipalities associated with mortality clusters for
      lung cancer belonged to various societal clusters. CONCLUSION: Increased
      mortality rates of colon and breast cancer can be explained by homogenous
      societal characteristics related to urbanisation, although there were exceptional
      areas with higher mortality rates. The regional variation in lung cancer
      mortality rate appeared to be due to heterogeneous factors. These findings and
      the analysis performed in the present study will contribute to both nationwide
      and region-specific cancer prevention strategies.

PMID- 15953395
TI  - Use of segmented CT transmission map to avoid metal artifacts in PET images by a
      PET-CT device.
AB  - BACKGROUND: Attenuation correction is generally used to PET images to achieve
      count rate values independent from tissue densities. The goal of this study was
      to provide a qualitative comparison of attenuation corrected PET images produced
      by a PET-CT device (CT, 120 kV, 40 mAs, FOV 600 mm) with and without segmentation
      of transmission data (ACseg+ and ACseg-respectively). Methods: The reconstructed
      images were compared to attenuation corrected images obtained with a high-energy
      transmission source (Cs-137 - 662 keV).Thirty oncologic patients were studied
      using CT and 137Cs for attenuation correction. All image data were acquired using
      the Gemini PET-CT scanner (Philips Medical Systems). It is an open PET-CT system
      that consists of the MX8000 multislice CT and the Allegro PET scanner arranged in
      a separable configuration. Images with ACseg+ and ACseg- were analyzed
      simultaneously in coronal, sagittal and transaxial planes. Two nuclear medicine
      physicians reviewed the image sets. Results: The image quality in the area of
      metal implants was better with ACseg+ than ACseg-, without metal induced
      artifacts generally observed in CT corrected images. Further the images with
      ACseg+ were qualitatively comparable to those obtained with 137Cs attenuation
      correction. Conclusions: In case of metal implants, PET studies corrected by CT
      should preferably use the ACseg+ method to avoid the image artifacts.

PMID- 15953396
TI  - Dishabituation of the BOLD response to speech sounds.
AB  - BACKGROUND: Neural systems show habituation responses at multiple levels,
      including relatively abstract language categories. Dishabituation - responses to
      non-habituated stimuli - can provide a window into the structure of these
      categories, without requiring an overt task. METHODS: We used an event-related
      fMRI design with short interval habituation trials, in which trains of stimuli
      were presented passively during 1.5 second intervals of relative silence between
      clustered scans. Trains of four identical stimuli (standard trials) and trains of
      three identical stimuli followed by a stimulus from a different phonetic category
      (deviant trials) were presented. This paradigm allowed us to measure and compare
      the time course of overall responses to speech, and responses to phonetic change.
      RESULTS: Comparisons between responses to speech and silence revealed strong
      responses throughout the extent of superior temporal gyrus (STG) bilaterally.
      Comparisons between deviant and standard trials revealed dishabituation responses
      in a restricted region of left posterior STG, near the border with supramarginal
      gyrus (SMG). Novelty responses to deviant trials were also observed in right
      frontal regions and hippocampus. CONCLUSION: A passive, dishabituation paradigm
      provides results similar to studies requiring overt responses. This paradigm can
      readily be extended for the study of pre-attentive processing of speech in
      populations such as children and second-language learners whose overt behavior is
      often difficult to interpret because of ancillary task demands.

PMID- 15953397
TI  - The World Summit on Sustainable Development: reaffirming the centrality of
      health.
AB  - The World Summit on Sustainable Development (WSSD) was held in Johannesburg in
      2002 to review progress since the Rio conference in 1992, and to agree a new
      global deal on sustainable development. Unlike its predecessor, it was primarily
      concerned with implementation rather than with new treaties and targets, although
      a number of new targets were agreed, for example one on sanitation. Failure to
      agree a target on renewable energy was regarded as a major disappointment of the
      conference. While relatively modest in its achievements, and with difficulties in
      achieving consensus in key areas such as energy, trade, finance and
      globalisation, WSSD nevertheless succeeded in placing sustainable development
      back on the political agenda, giving new impetus, in particular to the
      environment and development needs of Africa, with a strong focus on local issues
      like household energy, water and sanitation. Health was singled out as one of
      five priority areas, along with water, energy, agriculture and biodiversity, and
      was devoted a separate chapter in the resulting Plan of Implementation, which
      highlighted a range of environmental health issues as well as issues relating to
      health services, communicable and non-communicable diseases. A number of new
      partnerships were formed at WSSD, including the Healthy Environments for Children
      Alliance (HECA) launched by WHO, which will form an important platform for
      implementation. The Commission on Sustainable Development has been designated
      main responsibility for monitoring and follow up, with its programme of work
      reorganised to focus on thematic clusters of issues. From the perspective of
      health, WSSD must be seen as a reaffirmation of the central place of health on
      the sustainable development agenda, and in the broader context of a process which
      began in Rio and was given added impetus with the Monterrey Financing for
      Development conference and the World Trade Organisation meeting held in Doha.
      Translating policies into action at all levels- global to local - remains the
      single biggest challenge in the years that lie ahead.

PMID- 15953398
TI  - Nesprins: intracellular scaffolds that maintain cell architecture and coordinate
      cell function?
AB  - Nesprins are a recently discovered family of ubiquitously expressed intracellular
      proteins. Through alternative transcriptional initiation, termination and
      splicing, two genes - nesprin-1 and nesprin-2 (also known as syne-1 and syne-2) -
      give rise to many protein isoforms that vary markedly in size. The largest of
      these isoforms comprise a C-terminal transmembrane domain (the KLS domain) linked
      by a spectrin-repeat rod domain to an N-terminal paired, actin-binding, calponin
      homology domain. This structure suggests that they are well suited to orchestrate
      signalling between cell membranes and the cytoskeleton. Other isoforms have
      variable lengths of this rod domain linked to either end of the protein. Smaller
      isoforms with the KLS domain are localised at the inner nuclear membrane, where
      they bind lamin A/C and emerin. Larger nesprin isoforms link the outer nuclear
      membrane with intracellular organelles and the actin cytoskeleton and are thought
      to regulate nuclear anchorage and organelle migration. Thus, nesprins might have
      a variety of fundamental roles in cells, particularly muscle cells where they are
      highly expressed. We speculate that nesprin mutations might contribute to a broad
      range of human disease syndromes, including laminopathies.

PMID- 15953400
TI  - The prevalence of major congenital malformations during two periods of time, 1986
      1994 and 1995-2002 in newborns conceived by assisted reproduction technology.
AB  - Evidence has emerged that assisted reproduction technology (ART) may be
      associated with an increased risk of congenital malformations, low birth weight,
      and genetic imprinting disorders. The aim of the study was to determine, the
      prevalence of major malformations in newborns conceived by standard in vitro
      fertilization (IVF) in 1986-1994 and newborns conceived by different types of ART
      procedures in 1995-2002. Data were collected from the IVF Registry and Israel
      Birth Defects Monitoring System for all infants (live births, stillbirths and
      terminations of pregnancy) delivered after 20 weeks' gestation who achieved a
      fetal weight of at least 500 g. The control groups consisted of all spontaneously
      conceived babies (live births, stillbirths and terminations of pregnancy) born in
      our center during the same time periods. During the first period, a total of
      31,007 babies were born at our center, of whom 278 were conceived by standard
      IVF. Twenty-six of the IVF infants had major malformations, for a prevalence rate
      of 9.35%, which was 2.3-fold higher than that in the general population (4.05%).
      During the second period, 53,208 infants were born, of whom 1632 were conceived
      by ART. Major malformations were found in 147 ART infants, for a prevalence rate
      of 9.0%, which was 1.75-fold higher than in the general population (5.18%).
      Analysis of the clinical characteristics of the ART infants with major
      malformations showed that 70.3% were born preterm, 76.5% had low birth weight,
      58.6 were twins, and 11.7% were triplets. The use of ART procedures increased by
      a factor of 3.4 in the second period. Two important outcomes of ART were
      observed: an increased prevalence of major malformations about double the general
      population in both periods, and a high frequency of adverse clinical
      characteristics among ART infants with major malformations. Infertile couples
      should be adequately counseled regarding the real risk of having a child with
      malformations or a preterm or low birth weight infant.

PMID- 15953401
TI  - The role of genetic counseling on decisions of pregnant women aged 35 years or
      over regarding amniocentesis in Turkey.
AB  - We investigated the effects of genetic counseling given before amniocentesis that
      is given based on maternal serum screening (using the cut-off value of 1/250) and
      genetic sonogram results (+/- abnormal ultrasound marker) on pregnant women who
      are 35 years and older age. Their attitudes towards amniocentesis after genetic
      counseling were evaluated. Among 340 women, 223 (65.6%) were in the high-risk
      group and 117 (34.4%) were in the low-risk group according to non-invasive test
      results. After counseling, 216 pregnant women (167 cases have high-risk, 49 cases
      who had low-risk) decided to have amniocentesis while 124 women (56 with high
      risk and 68 with low-risk) declined it. Fourteen abnormal karyotypes were
      detected. All pregnant women who had fetuses with chromosomal aberrations were in
      high-risk group. Our study shows that screening by non-invasive prenatal
      diagnostic tool has an effect on families' choice of amniocentesis. The use of
      these test results during counseling decreased the number of amniocentesis in a
      ratio of 36.5%.

PMID- 15953402
TI  - Vitamin E deficiency ataxia with (744 del A) mutation on alpha-TTP gene: genetic
      and clinical peculiarities in Moroccan patients.
AB  - Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease
      characterized clinically by neurological symptoms with often striking resemblance
      to those of Friedreich's ataxia (FA). Molecular analysis is needed for an early
      differential diagnosis, in order to initiate therapeutic vitamin E
      supplementation before damage develops. We studied 16 patients from seven
      Moroccan families presenting an autosomal recessive Friedreich-like ataxia with
      vitamin E deficiency. Our patients were homozygous for 744 del A mutation of
      alpha-TTP gene. Compilation of clinical records revealed a great phenotypic
      variability and some features indicating a new possible role of vitamin E in
      hypothalamo-hypophysial system regulation and cardiomyopathy prevention. Early
      vitamin E supplementation may provide considerable improvement of neurological
      signs and other associated abnormalities. Clinical heterogeneity is for
      involvement of other non-genetic defect and indicated another role of vitamin E,
      which should be better studied.

PMID- 15953403
TI  - Haplotypes Eco47 III-Nsp I sites frequencies on the IDUA gene in Mexican native
      population.
AB  - BACKGROUND: The frequency of haplotypes of Nsp I-Eco47 III sites, at the IDUA
      (alpha-L iduronidase) gene, in Huichol, Tarahumara and Mestizo Mexican population
      is reported. METHODS: Eco47 III and Nsp I intragenic polymorphisms in IDUA gene
      are studied in three (Mestizo, Huichol and Tarahumara populations) Mexican
      groups. Data from normal Australian [Hum. Genet. 90 (1992) 327] individuals were
      considered for comparative analyses. RESULTS: The genotypes for IDUA Eco47 III
      and Nsp I sites in Mexicans were in agreement with Hardy-Weinberg equilibrium.
      Allele frequency distributions for individual sites differed (P < 0.05) except at
      site B1 in the Huichol group. Haplotype Eco47 III-Nsp I frequency distributions
      were different in the three Mexican normal groups, and it was also observed when
      to compared with the normal Australians. CONCLUSIONS: This characteristic makes
      the two IDUA polymorphic sites useful for identification purposes, and these
      polymorphisms could be included in a PCR based battery of DNA markers.

PMID- 15953404
TI  - FISH approach to determine cat eye syndrome chromosome breakpoints of a patient
      with cat eye syndrome type II.
AB  - We report a 19-year-old man with craniofacial dysmorphic features, anorectal
      malformations, eye colobomas, orthopaedic anomalies, and mild neurodevelopmental
      delay. Cat eye syndrome (CES) was suspected, and confirmed by cytogenetic
      analysis which showed the presence of a supernumerary bisatellited chromosome,
      identified by fluorescence in situ hybridization (FISH) as invdup(22). The marker
      was further analyzed with six BAC clones located at the 22q11.1 and 22q11.2
      regions; this analysis allowed correct assignment at low copy repeat 4 on
      chromosome 22 (LCR22-4) of the two breakpoints, confirming the presence of a CES
      chromosome type II. The patient's phenotype is considered in the light of the
      cytogenetic, and FISH investigations results and other patients reported in
      literature. Molecular definition of the breakpoints at the LCR22-4 copy confirms
      the role of different chromosome 22-specific LCRs in CES chromosomes generation,
      as well as in other chromosome 22 germ line rearrangements. Our report confirms
      that, unlike other conditions, i.e. the invdup(15) bisatellited dicentric marker,
      the CES phenotype does not appear to correlate with the size of the marker
      chromosome. Additional cases are necessary to be able to draw more specific
      genotype-phenotype correlations and to determine the outcome of patients with
      CES, especially when this rare condition is diagnosed in prenatal age.

PMID- 15953405
TI  - Interphase-FISH study in three patients with tetraploid/diploid mosaicism.
AB  - We report tetraploid/diploid mosaicism in a boy and two girls detected by
      cultured skin fibroblasts. In all these children, interphase-FISH using DXZ1
      probe confirmed the original karyotype. Tetraploid mosaicism was also confirmed
      by alpha-satellite probes from chromosomes 2, 6, 7, 9, 10, 17, 18 and Y in
      fibroblasts from the boy. The common features in these children are failure to
      thrive, slight mental deficiency and some degree of body asymmetry. The advantage
      of using interphase-FISH is the possibility of analysing a great number of cells
      in short time, thus giving a more precise percentage with regard to abnormal
      cells.

PMID- 15953406
TI  - Polycystic kidneys and del (4)(q21.1q21.3): further delineation of a distinct
      phenotype.
AB  - A three year-old boy was evaluated because of growth and developmental delay,
      hypotonia and dysmorphic features. G-banding analysis revealed a small
      interstitial deletion of the long arm of chromosome four described as 46,XY,del
      (4)(q21.1q21.3). This patient's findings on physical exam included relative
      macrocephaly, frontal bossing, short fingers with clinodactyly and were
      consistent with the phenotypes of previously reported deletions involving the
      4q21--> 4q22 band region (Am. J. Med. Genet. 68 (1997) 400-405). To date there
      are 10 reported live-born cases with such deletions and similar features. The
      case reported here delimits a minimal critical region for this phenotype to
      chromosomal region 4q21. Our patient was also found to have cysts in both his
      kidneys. The gene for type II polycystic kidney disease (PKD2) has been mapped to
      chromosomal region 4q21--> 4q23. FISH analysis, with a probe including the PKD2
      gene, demonstrated hemizygosity at this locus. Thus the absence of one of the
      PKD2 alleles in the case reported here is associated with early bilateral cyst
      development. Kidney ultrasound/autopsy studies were reported in seven of the
      patients with the characteristic phenotype, and were positive for cysts in four
      cases including the one presented here (Clin. Genet. 31 (1987) 199-205; Am. J.
      Med. Genet. 68 (1997) 400-405; Am. J. Med. Genet. 40 (1991) 77-790. Our report
      supports the presence of a distinct phenotype associated with a deleted
      chromosomal region within 4q21. Hemizygosity for the PKD2 gene is likely in such
      deletions and may lead to renal cyst formation.

PMID- 15953407
TI  - Atypical 18p- syndrome associated with partial trisomy 16p in a chromosomally
      unbalanced child of consanguineous parents with an identical balanced
      translocation.
AB  - A 2 month old male infant was found to have mild growth retardation, prominent
      forehead, low set ears, low nasal bridge, rounded facies, cleft palate, webbed
      neck, shawl scrotum, and absent right kidney. The propositus, a product of a
      consanguineous marriage, had extremely rare abnormal cytogenetic findings. His
      karyotype contained three derivative chromosomes that originated from a familial
      translocation, t(16;18)(p13.3;p11.2) carried by both parents. Based on parental
      studies, the infant's unbalanced karyotype was defined as:
      [46,XY,t(16;18)(p13.3;p11.2), der(18)t(16;18).ish t(16;18)(16ptel
      ,16qtel+,18ptel+,wcp16+,wcp18+;16ptel+,18ptel-,wcp16+,wcp18+),
      der(18)t(16;18)(16ptel+,18ptel-,wcp16+,wcp18+)]. We describe this child at 2
      months of age with a follow up at 4 1/2 years, exhibiting a mixed clinical
      picture with features of both 18p- and partial trisomy 16p13.3.

PMID- 15953408
TI  - Double aneuploidy involving trisomy 7 with Potter sequence.
AB  - We report a prenatal case of double aneuploidy (consisting of chromosome 7 and X)
      with the features of Potter sequence. Of the stillborn fetus, skin fibroblast
      cultures were performed and fluorescence in situ hybridization (FISH) technique
      was also used for further investigation. On physical examination; the fetus was
      found to have malformed ears, micrognatia, hypertelorism, abnormal extremities,
      rocker-bottom feet and abnormal external genitalia and polycystic right kidney
      was seen after an extensive autopsy. As amniocentesis and cordocentesis materials
      revealed X chromosome mosaicism, trisomy 7 was detected in the skin fibroblast
      culture of the ex fetus and karyotype evaluated as composite; 46~47,X,+7,
      X[cp18]. FISH results confirmed the double aneuploidy and also revealed XX and
      XXXX cell lines. Comparison with the previously reported cases of trisomy 7 with
      Potter syndrome suggests a possible link (if not coincidental) between trisomy 7
      and Potter syndrome in our case. This is the first reported case of double
      aneuploidy involving trisomy 7 with the features of Potter syndrome.

PMID- 15953409
TI  - Double aneuploidy mosaicism with Down-Klinefelter's syndrome.

PMID- 15953410
TI  - Getting RIP'd Stunts Your Growth.
AB  - The p75 neurotrophin receptor (p75NTR) collaborates with the Nogo receptor (NgR)
      and LINGO-1 to activate RhoA in response to myelin-based growth inhibitors such
      as myelin-associated glycoprotein (MAG). In this issue of Neuron, Domeniconi et
      al., in a surprising turn, show that MAG induces intramembrane proteolysis (RIP)
      of p75NTR and find that p75NTR cleavage is required for MAG-induced RhoA
      activation and growth inhibition.

PMID- 15953411
TI  - DISCO! Dissociation of cone opsins: the fast and noisy life of cones explained.
AB  - Vertebrate retinas contain two types of photoreceptors. Rods are for vision in
      dim light, while cones provide high-speed color vision in bright light. In this
      issue of Neuron, Kefalov et al. present data to explain the reduced sensitivity
      and faster response kinetics of cones. They show that the chromophore dissociates
      from cone but not rod visual pigment, yielding apo-opsin. This apo-opsin
      activates the signaling cascade to desensitize cones and speed the photoresponse.

PMID- 15953412
TI  - Building better models of visual cortical receptive fields.
AB  - Scientists usually study the receptive fields of visual cortical neurons by
      measuring responses to "optimal stimuli." In this issue of Neuron, Rust and
      colleagues have taken a promising alternative approach: build a receptive field
      model based on the cell responses to a stimulus subset and then use the model to
      predict responses to other stimuli.

PMID- 15953413
TI  - Breaks in coordination: DNA repair in inherited ataxia.
AB  - Genetic defects in DNA repair are increasingly recognized as being able to cause
      degenerative ataxia syndromes. It remains a mystery, however, why disruption of a
      process fundamental to proliferating cells can be selectively toxic to
      postmitotic neurons. Recent studies now reveal that an ataxia gene, tyrosyl
      phosphodiesterase 1 (TDP1), repairs single-stranded DNA breaks in nondividing
      cells. Here we review the implications of this and other findings for a growing
      list of hereditary ataxias.

PMID- 15953414
TI  - MAG induces regulated intramembrane proteolysis of the p75 neurotrophin receptor
      to inhibit neurite outgrowth.
AB  - The three known inhibitors of axonal regeneration present in myelin--MAG, Nogo,
      and OMgp--all interact with the same receptor complex to effect inhibition via
      protein kinase C (PKC)-dependent activation of the small GTPase Rho. The
      transducing component of this receptor complex is the p75 neurotrophin receptor.
      Here we show that MAG binding to cerebellar neurons induces alpha- and then gamma
      secretase proteolytic cleavage of p75, in a protein kinase C-dependent manner,
      and that this cleavage is necessary for both activation of Rho and inhibition of
      neurite outgrowth.

PMID- 15953415
TI  - Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease.
AB  - Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to
      neurodegeneration and the characteristic symptoms of Lewy body disease (LBD).
      Since previous studies suggest that immunization might be a potential therapy for
      Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn
      might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic
      (tg) mice were vaccinated with halpha-syn. In mice that produced high relative
      affinity antibodies, there was decreased accumulation of aggregated halpha-syn in
      neuronal cell bodies and synapses that was associated with reduced
      neurodegeneration. Furthermore, antibodies produced by immunized mice recognized
      abnormal halpha-syn associated with the neuronal membrane and promoted the
      degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar
      effects were observed with an exogenously applied FITC-tagged halpha-syn
      antibody. These results suggest that vaccination is effective in reducing
      neuronal accumulation of halpha-syn aggregates and that further development of
      this approach might have a potential role in the treatment of LBD.

PMID- 15953416
TI  - Clathrin-dependent and clathrin-independent retrieval of synaptic vesicles in
      retinal bipolar cells.
AB  - Synaptic vesicles can be retrieved rapidly or slowly, but the molecular basis of
      these kinetic differences has not been defined. We now show that substantially
      different sets of molecules mediate fast and slow endocytosis in the synaptic
      terminal of retinal bipolar cells. Capacitance measurements of membrane retrieval
      were made in terminals in which peptides and protein domains were introduced to
      disrupt known interactions of clathrin, the AP2 adaptor complex, and amphiphysin.
      All these manipulations caused a selective inhibition of the slow phase of
      membrane retrieval (time constant approximately 10 s), leaving the fast phase
      (approximately 1 s) intact. Slow endocytosis after strong stimulation was
      therefore dependent on the formation of clathrin-coated membrane. Fast
      endocytosis occurring after weaker stimuli retrieves vesicle membrane in a
      clathrin-independent manner. All compensatory endocytosis required GTP
      hydrolysis, but only a subset of released vesicles were primed for fast, clathrin
      independent endocytosis.

PMID- 15953417
TI  - Breaking the covalent bond--a pigment property that contributes to
      desensitization in cones.
AB  - Retinal rod and cone pigments consist of an apoprotein, opsin, covalently linked
      to a chromophore, 11-cis retinal. Here we demonstrate that the formation of the
      covalent bond between opsin and 11-cis retinal is reversible in darkness in
      amphibian red cones, but essentially irreversible in red rods. This dissociation,
      apparently a general property of cone pigments, results in a surprisingly large
      amount of free opsin--about 10% of total opsin--in dark-adapted red cones. We
      attribute this significant level of free opsin to the low concentration of
      intracellular free 11-cis retinal, estimated to be only a tiny fraction
      (approximately 0.1 %) of the pigment content in red cones. With its constitutive
      transducin-stimulating activity, the free cone opsin produces an approximately 2
      fold desensitization in red cones, equivalent to that produced by a steady light
      causing 500 photoisomerizations s-1. Cone pigment dissociation therefore
      contributes to the sensitivity difference between rods and cones.

PMID- 15953418
TI  - G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels.
AB  - Voltage-dependent G protein (Gbetagamma) inhibition of N-type (CaV2.2) channels
      supports presynaptic inhibition and represents a central paradigm of channel
      modulation. Still controversial are the proposed determinants for such
      modulation, which reside on the principal alpha1B channel subunit. These include
      the interdomain I-II loop (I-II), the carboxy tail (CT), and the amino terminus
      (NT). Here, we probed these determinants and related mechanisms, utilizing
      compound-state analysis with yeast two-hybrid and mammalian cell FRET assays of
      binding among channel segments and G proteins. Chimeric channels confirmed the
      unique importance of NT. Binding assays revealed selective interaction between NT
      and I-II elements. Coexpressing NT peptide with Gbetagamma induced constitutive
      channel inhibition, suggesting that the NT domain constitutes a G protein-gated
      inhibitory module. Such inhibition was limited to NT regions interacting with I
      II, and G-protein inhibition was abolished within alpha1B channels lacking these
      NT regions. Thus, an NT module, acting via interactions with the I-II loop,
      appears fundamental to such modulation.

PMID- 15953419
TI  - Rap2-JNK removes synaptic AMPA receptors during depotentiation.
AB  - The related small GTPases Ras and Rap1 are important for signaling synaptic AMPA
      receptor (-R) trafficking during long-term potentiation (LTP) and long-term
      depression (LTD), respectively. Rap2, which shares 60% identity to Rap1, is
      present at excitatory synapses, but its functional role is unknown. Here, we
      report that Rap2 activity, stimulated by NR2A-containing NMDA-R activation,
      depresses AMPA-R-mediated synaptic transmission via activation of JNK rather than
      Erk1/2 or p38 MAPK. Moreover, Rap2 controls synaptic removal of AMPA-Rs with long
      cytoplasmic termini during depotentiation. Thus, Rap2-JNK pathway, which opposes
      the action of the NR2A-containing NMDA-R-stimulated Ras-ERK1/2 signaling and
      complements the NR2B-containing NMDA-R-stimulated Rap1-p38 MAPK signaling,
      channels the specific signaling for depotentiating central synapses.

PMID- 15953420
TI  - NCAM 180 acting via a conserved C-terminal domain and MLCK is essential for
      effective transmission with repetitive stimulation.
AB  - NCAM 180 isoform null neuromuscular junctions are unable to effectively mobilize
      and exocytose synaptic vesicles and thus exhibit periods of total transmission
      failure during high-frequency repetitive stimulation. We have identified a highly
      conserved C-terminal (KENESKA) domain on NCAM that is required to maintain
      effective transmission and demonstrate that it acts via a pathway involving MLCK
      and probably myosin light chain (MLC) and myosin II. By perfecting a method of
      introducing peptides into adult NMJs, we tested the hypothesized role of proteins
      in this pathway by competitive disruption of protein-protein interactions. The
      effects of KENESKA and other peptides on MLCK and MLC activation and on failures
      in both wild-type and NCAM 180 null junctions supported this pathway, and serine
      phosphorylation of KENESKA was critical. We propose that this pathway is required
      to replenish synaptic vesicles utilized during high levels of exocytosis by
      facilitating myosin-driven delivery of synaptic vesicles to active zones or their
      subsequent exocytosis.

PMID- 15953421
TI  - Mu-opioid receptor and CREB activation are required for nicotine reward.
AB  - Environmental cues associated with nicotine delivery are an important part of the
      stimulus that sustains smoking behavior and is often coupled with craving and
      relapse; however, the neuronal circuitry and molecular substrates underlying this
      process are still poorly understood. Exposure to an environment previously
      associated with rewarding properties of nicotine results in an increase of CREB
      phosphorylation similar to that seen following nicotine administration, and this
      response is absent in MOR(-/-) mice. Moreover, a single administration of an
      opioid receptor antagonist, naloxone, blocks both the conditioned molecular
      response (CREB phosphorylation) and the conditioned behavioral response (nicotine
      reward) in a place preference paradigm. Lastly, repeated nicotine administration
      results in increased expression of MORs. However, this effect, along with
      rewarding properties of nicotine, is blocked in mice with a targeted disruption
      in the CREB gene. Together, pharmacologic and genetic manipulations indicate that
      phosphorylation of CREB and upregulation of functional MORs are required for
      nicotine-conditioned reward.

PMID- 15953422
TI  - Spatiotemporal elements of macaque v1 receptive fields.
AB  - Neurons in primary visual cortex (V1) are commonly classified as simple or
      complex based upon their sensitivity to the sign of stimulus contrast. The
      responses of both cell types can be described by a general model in which the
      outputs of a set of linear filters are nonlinearly combined. We estimated the
      model for a population of V1 neurons by analyzing the mean and covariance of the
      spatiotemporal distribution of random bar stimuli that were associated with
      spikes. This analysis reveals an unsuspected richness of neuronal computation
      within V1. Specifically, simple and complex cell responses are best described
      using more linear filters than the one or two found in standard models. Many
      filters revealed by the model contribute suppressive signals that appear to have
      a predominantly divisive influence on neuronal firing. Suppressive signals are
      especially potent in direction-selective cells, where they reduce responses to
      stimuli moving in the nonpreferred direction.

PMID- 15953423
TI  - Placebo in emotional processing--induced expectations of anxiety relief activate
      a generalized modulatory network.
AB  - Placebo analgesia and reward processing share several features. For instance,
      expectations have a strong influence on the subsequent emotional experience of
      both. Recent imaging data indicate similarities in the underlying neuronal
      network. We hypothesized that placebo analgesia is a special case of reward
      processing and that placebo treatment could modulate emotional perception in the
      same way as does pain perception. The behavioral part of this study indicates
      that placebo treatment has an effect on how subjects perceive unpleasant
      pictures. Furthermore, event-related fMRI demonstrated that the same modulatory
      network, including the rostral anterior cingulate cortex and the lateral
      orbitofrontal cortex, is involved in both emotional placebo and placebo
      analgesia. These effects were correlated with the reported placebo effect and
      were predicted by the amount of treatment expectation induced on a previous day.
      Thus, the placebo effect may be considered to be a general process of modulation
      induced by the subjects' expectations.

PMID- 15953424
TI  - Nerve growth factor concentration and implications in photorefractive keratectomy
      vs laser in situ keratomileusis.
AB  - PURPOSE: To determine whether tear nerve growth factor (NGF) concentration
      correlates with corneal sensation and ocular surface dryness after
      photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK).
      DESIGN: Prospective, nonrandomized comparative clinical trial. METHODS: Seventy
      eyes of 35 patients and 76 eyes of 38 patients underwent PRK and LASIK procedures
      to correct myopia and myopic astigmatism, respectively. Total tear protein level,
      tear NGF concentration, tear film breakup time (BUT) and Schirmer values were
      measured before and 1 day, 1 week, 1 month, 3 months, and 6 months after surgery.
      RESULTS: The postoperative mean tear NGF/total tear protein (NGF/tP) ratio
      increased in both PRK and LASIK patients compared with preoperative levels (P <
      .0001). At 1 week and 1 month postoperatively, the NGF/tP ratio was higher in PRK
      than in LASIK subjects (P < .0001). Before 6 months postoperatively, the mean
      corneal sensation after LASIK in the ablated zone was lower than the preoperative
      sensation (P < .0001), but this was not the case in PRK subjects. Mean BUT and
      Schirmer values were significantly lower in LASIK-treated eyes compared with PRK
      treated eyes up to 6 months postoperatively (P < .0001). The early postoperative
      tear NGF/tP ratio correlated with the postoperative 6-month value of corneal
      sensation, BUT, and Schirmer values. CONCLUSIONS: The difference in the
      postoperative corneal sensation and ocular surface dryness between PRK-treated
      and LASIK-treated eyes might be related to the difference in the early
      postoperative levels of NGF, which is a potent nerve growth stimulator.

PMID- 15953425
TI  - Intravitreal versus retrobulbar injections of triamcinolone for macular edema
      associated with branch retinal vein occlusion.
AB  - PURPOSE: To compare the short-term effect of intravitreal versus retrobulbar
      injection of triamcinolone acetonide for the treatment of macular edema caused by
      branch retinal vein occlusion. DESIGN: Randomized clinical trial. METHODS: Sixty
      eyes of 60 patients who had macular edema associated with branch retinal vein
      occlusion were randomly assigned to receive a single intravitreal injection (4
      mg) or repeated retrobulbar injections (40 mg, three times) of triamcinolone.
      These injections (first injection in the retrobulbar group) were given
      approximately 1 week after focal laser photocoagulation. Using optical coherence
      tomography, the central retinal (foveal) thickness and total macular volume were
      measured before and at 1 and 3 months after injection. Visual acuity, intraocular
      pressure, and the incidence of reinjection were also examined. Fifty-two patients
      (86.7%) completed the 3-month follow-up. RESULTS: The mean foveal thickness and
      total macular volume decreased significantly after either intravitreal or
      repeated retrobulbar triamcinolone injections. Foveal thickness and macular
      volume were significantly less after intravitreal injection than after repeated
      retrobulbar injections, although there had been no significant differences at
      baseline. The percent reductions in foveal thickness and macular volume were also
      greater after intravitreal injection than after retrobulbar injections.
      Improvement in visual acuity was significantly better after intravitreal
      injection than after the retrobulbar injections. The incidence of intraocular
      pressure rise (to > or =20 mm Hg) was greater in the intravitreal group than in
      the retrobulbar group, but this was readily controlled by the use of antiglaucoma
      medications. After completion of the 3-month follow-up, 24 patients (46.2%)
      underwent reinjection. The need for reinjections was significantly greater in the
      retrobulbar group than in the intravitreal group (P = .0001). CONCLUSIONS: A
      single intravitreal injection of triamcinolone is significantly more effective
      than are repeated retrobulbar injections in reducing macular edema associated
      with branch retinal vein occlusion, and leads to greater improvement in visual
      acuity.

PMID- 15953426
TI  - Acute-onset endophthalmitis after cataract surgery (2000-2004): incidence,
      clinical settings, and visual acuity outcomes after treatment.
AB  - PURPOSE: To report the incidence, clinical settings, and visual acuity outcomes
      of acute-onset endophthalmitis after cataract surgery. DESIGN: Retrospective,
      observational case series. METHODS: Annual cataract surgery statistics were
      determined by review of electronic surgical records. The clinical and
      microbiologic records were reviewed of all patients with clinically diagnosed
      endophthalmitis within 6 weeks after cataract surgery at a single university
      affiliated hospital between January 2000 and November 2004. main outcome
      measures: Operative technique, intraoperative complications, and visual acuity.
      RESULTS: The incidence of acute-onset endophthalmitis after cataract surgery was
      0.04% (7/15,920) for cataract surgeries of all methods, 0.05% (6/11,462) for
      cataract surgery by clear cornea phacoemulsification, and 0.02% (1/4,458) for
      cataract surgery by methods other than clear cornea phacoemulsification (P =
      .681, Fisher's exact test). Six of seven (86%) cases occurred in the right eye,
      and all cases were performed by right-handed surgeons through temporal incisions.
      Five of seven (71%) patients had relative immune compromise. Four of seven (57%)
      patients had an intraoperative complication: vitreous loss in three patients and
      iris prolapse in one patient. Two patients had topical placement of lidocaine 2%
      gel before povidone-iodine preparation. The visual acuity at final follow up was
      20/25 or better in four patients and count fingers or worse in three patients.
      CONCLUSIONS: The incidence of acute-onset endophthalmitis after temporal clear
      cornea incision phacoemulsification is low (0.05%). Potential risk factors for
      endophthalmitis may include intraoperative complications, relative immune
      compromise, application of lidocaine 2% gel before povidone-iodine preparation,
      and inferior incision location.

PMID- 15953427
TI  - The development of complications in patients with chronic anterior uveitis.
AB  - PURPOSE: This study aimed to identify the factors determining the ocular
      complications and visual outcome in patients with chronic anterior uveitis.
      DESIGN: Retrospective, noncomparative case study. METHODS: Ninety-one eyes of 68
      patients with anterior uveitis that lasted longer than 3 months were assessed.
      Patients were divided into idiopathic and nonidiopathic chronic anterior uveitis
      and Fuchs' heterochromic uveitis. Visual acuity and complications such as
      posterior synechiae, cataract formation, raised intraocular pressure (IOP), and
      posterior segment complications (i.e., cystoid macular edema and optic nerve
      involvement) were evaluated. Poor visual outcome measured by life-table analysis
      was considered when logMAR (log of the reciprocal of Snellen visual acuity)
      visual acuity was 0.3 or worse. RESULTS: No statistically significant differences
      in the visual outcome were found between the three groups of patients with
      chronic anterior uveitis. Posterior synechiae formation was, as expected,
      significantly increased in patients with chronic anterior uveitis compared with
      those with Fuchs' heterochromic uveitis. There was a trend for patients with
      nonidiopathic chronic anterior uveitis to have an increased risk of cystoid
      macular edema compared with those with idiopathic disease. There were no
      significant differences in visual outcome between any of the groups with time.
      CONCLUSIONS: The visual prognosis for patients with chronic anterior uveitis is
      generally good. Posterior segment complications appear to be more likely to occur
      if there is an underlying associated disease. However, the presence of
      complications does not seem to affect the visual outcome in patients with chronic
      anterior uveitis.

PMID- 15953428
TI  - Cataract progression after intravitreal triamcinolone injection.
AB  - PURPOSE: To assess cataract progression after intravitreal triamcinolone
      injection. DESIGN: Retrospective, interventional, case-control study. METHODS:
      Forty-two phakic eyes of 37 patients were injected one, two, or three times with
      intravitreal triamcinolone for various indications. Noninjected phakic fellow
      eyes served as the control. The mean follow-up time for single injection was 12
      months, for multiple injections was 14 months, and for control group was 13
      months. Lens status, best-corrected visual acuity, and refractive errors were
      recorded at baseline and at each follow-up examination. RESULTS: At the last
      follow-up, changes in posterior subcapsular cataract and refractive error from
      baseline were significantly different between single triamcinolone-injected eyes
      and the control group [0.7 +/- 0.2 (mean +/- SEM [arbitrary unit] vs 0.2 +/- 0.1,
      P = .02; and -0.5 +/- 0.1 diopter vs -0.2 +/- 0.1 diopter, P = .01,
      respectively). For multiple-injected eyes and control eyes, change from baseline
      in corticonuclear cataract (1.1 +/- 0.2 vs 0.2 +/- 0.1), posterior subcapsular
      cataract (1.1 +/- 0.2) and refractive error (-1.8 +/- 0.4 diopters) were
      significantly different (P < .001, P < .001, and P < .001, respectively). Visual
      acuity did not change after single injection (P = .83) and in control group (P =
      .19) but decreased after multiple injections (P = .006). Eleven study eyes and
      two control group eyes underwent cataract extraction during study period.
      Corticonuclear and posterior subcapsular cataract progression significantly
      correlated with follow-up time (P = .003 and P = .02, respectively) and number of
      injections (P = .01 and P = .04, respectively). CONCLUSIONS: Single intravitreal
      triamcinolone injection induces posterior subcapsular cataract development,
      whereas multiple injections result in all-layer cataract progression.

PMID- 15953429
TI  - Predictive factors for progressive optic nerve damage in various types of chronic
      open-angle glaucoma.
AB  - PURPOSE: To evaluate whether various types of chronic open-angle glaucoma differ
      in predictive factors for progression of glaucomatous optic nerve damage. DESIGN:
      Observational cohort study. METHODS:  SETTING: Prospective observational clinical
      study. PATIENTS: 517 eyes of 300 Caucasian patients with chronic open-angle
      glaucoma with elevated intraocular pressure (primary open-angle glaucoma, n =
      289; secondary open-angle glaucoma, n = 50) and with normal intraocular pressure
      (n = 178). OBSERVATION PROCEDURE: During follow-up (median: 49 months, 6 months
      130 months), all patients underwent repeated evaluation of color stereo optic
      disk photographs and white-on-white visual field examination. MAIN OUTCOME
      MEASURES: Progression of glaucoma was defined as neuroretinal rim loss during the
      study period. RESULTS: For patients with elevated intraocular pressure,
      significantly predictive factors for eventual progression were older age,
      advanced perimetric damage, smaller neuroretinal rim, and larger area of beta
      zone of parapapillary atrophy. In contrast, in the normal intraocular pressure
      group, a significant predictive factor was presence of disk hemorrhages at
      baseline. Within the patients with elevated intraocular pressure, the primary
      open-angle glaucoma group and the secondary open-angle glaucoma group did not
      differ in predictive factors for progression of glaucoma. CONCLUSIONS: Open-angle
      glaucoma patients with normal intraocular pressure and open-angle glaucoma
      patients with elevated intraocular pressure differ in predictive factors for
      eventual progression of glaucomatous optic nerve damage. It may have clinical
      importance and may be helpful in the discussion of the pathogenesis of the
      glaucomas.

PMID- 15953430
TI  - Use of progressive glaucomatous optic disk change as the reference standard for
      evaluation of diagnostic tests in glaucoma.
AB  - PURPOSE: Progressive change in optic disk appearance has been suggested as the
      best available reference standard for glaucoma diagnosis. We evaluated the
      accuracy of scanning laser polarimetry (SLP) with variable corneal compensation
      to discriminate patients with documented progressive optic disk change from
      healthy subjects. DESIGN: Observational case-control study. METHODS: Glaucoma
      patients with documented evidence of progressive optic disk change as assessed by
      stereoscopic photographs were selected. Healthy control subjects had normal
      visual fields and normal clinical examination. All subjects underwent imaging
      with the GDx VCC scanning laser polarimeter. Receiver-operating characteristic
      (ROC) curves, sensitivities at fixed specificities, and likelihood ratios were
      calculated. RESULTS: Sixty-five eyes were healthy control patients. Seventy-one
      eyes had progressive optic disk change, of which 41 (58%) had abnormal visual
      field tests closest to the imaging date (perimetric glaucomatous optic neuropathy
      [GON]), and 30 (42%) eyes had normal visual fields (preperimetric GON). The GDx
      VCC parameter nerve fiber indicator performed best for discrimination between
      perimetric GON and normal eyes (AUC = 0.94; sensitivity = 93% for specificity >
      or =80%) as well as for the discrimination between preperimetric GON and normal
      eyes (AUC = 0.89; sensitivity = 83% for specificity > or =80%). CONCLUSION: SLP
      differentiated patients with documented progressive optic disk change from normal
      subjects and detected abnormalities in patients with confirmed diagnosis of
      preperimetric GON, suggesting that it may be useful for early glaucoma diagnosis.
      We suggest that progressive optic disk change should be used in the evaluation of
      diagnostic accuracy of imaging instruments for glaucoma.

PMID- 15953431
TI  - Laser in situ keratomileusis for primary and secondary mixed astigmatism.
AB  - PURPOSE: To evaluate and compare the efficacy, predictability, and safety of
      LASIK in the correction of primary and secondary mixed astigmatism after previous
      LASIK surgery. DESIGN: Retrospective, comparative case series. METHODS: The
      retrospective study included 118 eyes having LASIK with the LADARVison 4000
      excimer laser (Alcon Surgical, Orlando, Florida) to correct mixed astigmatism.
      The eyes were divided into two groups: in group A (n = 64), LASIK was for primary
      mixed astigmatism and in group B (n = 54), LASIK was for secondary mixed
      astigmatism. Mean follow-up was 10.6 +/- 5.90 months. RESULTS: Overall, the
      postoperative UCVA was 20/20 in 51% of eyes and 20/40 or better in 97% of eyes at
      the last visit. The mean refractive cylinder was -2.18 +/- 0.94 D preoperatively
      and -0.56 +/- 0.56 D postoperatively. Sixty-one percent of eyes had a refractive
      cylinder of 0.50 D or less. One eye lost 2 lines of BSCVA (0.8%). None of the
      eyes had postoperative BSCVA worse than 20/25. The difference of preoperative
      cylinder was significant between group A and group B (P = .000). However, there
      was no statistical difference of postoperative refraction and UCVA between these
      two groups. At 12 months, the mean vector magnitude achieved was 93% of intended
      cylinder correction with a mean angle of error of -3.0 +/- 16 degrees.
      CONCLUSIONS: LASIK is a safe, effective, and predictable procedure to treat both
      primary and secondary mixed astigmatism. Nomogram adjustment with spherical and
      astigmatism components individually may improve refractive outcomes.

PMID- 15953432
TI  - Incidence of cytomegalovirus (CMV) retinitis in second eyes of patients with the
      acquired immune deficiency syndrome and unilateral CMV retinitis.
AB  - PURPOSE: To evaluate the risk and risk factors for developing cytomegalovirus
      (CMV) retinitis in previously uninvolved second eyes among patients with
      unilateral CMV retinitis. DESIGN: Cohort study. METHODS:  SETTINGS: Single-center
      academic AIDS ophthalmology practice. PATIENT POPULATION: Three hundred seventy
      six consecutive patients with AIDS and unilateral CMV retinitis were followed
      from the time of CMV retinitis diagnosis for the development of second-eye
      retinitis. EXPERIMENTAL PROCEDURES: Demographic and clinical characteristics were
      noted at baseline. Use of highly active antiretroviral therapy (HAART) and immune
      recovery in response to HAART were noted prospectively. MAIN OUTCOME MEASURE:
      Development of CMV retinitis in a previously uninvolved eye. RESULTS: Ninety-one
      percent of subjects received systemic anti-CMV treatment. Second-eye retinitis
      occurred in 26.1%/person-year (19.6% within the first 6 months), less than half
      the rate previously reported in untreated groups. Initial CD4+ T cell count >12
      cells/microl, use of HAART, and initial posterior pole involvement were
      associated with 64%, 46%, and 41% reductions in incidence vis-a-vis comparison
      groups. Benefit from HAART was limited to that subset who developed immune
      recovery of a degree expected to restore innate control of CMV (a rise in the
      CD4+ T cell count by >50 cells/microl to a level >100 cells/microl). CONCLUSIONS:
      The risk of second-eye retinitis is substantial in patients with unilateral CMV
      retinitis but appears to be reduced by anti-CMV therapy and by HAART-induced
      immune recovery. Patients are at highest risk when CD4+ T cell counts are very
      low and in the months immediately after CMV retinitis diagnosis.

PMID- 15953433
TI  - Postoperative corneal swelling correlates strongly to corneal endothelial cell
      loss after phacoemulsification cataract surgery.
AB  - PURPOSE: To evaluate postoperative corneal swelling as a predictor of corneal
      endothelial cell loss after phacoemulsification cataract surgery. DESIGN:
      Prospective observational case series. METHODS: Thirty patients planned for
      routine phacoemulsification cataract surgery were included. Ultrasonic pachymetry
      and specular microscope endothelial photography of the central and nasal portions
      of the cornea and Orbscan II slit-scan tomography were performed preoperatively
      and the day after surgery. The 30 patients were selected from 41 patients based
      on their increase in central corneal thickness: the first 10 cases with a <5%
      increase, the first 10 with a 6% to 20% increase, and the first 10 with a > or
      =20% increase. The same measurements were repeated after 1, 2, and 3 months. The
      primary outcome measures were corneal endothelial cell loss and increase in
      pachymetry. Several other parameters were also registered, including age, degree
      of cataract, visual acuity, phacoemulsification time and energy, total operation
      time, and the amount of infusion fluid used. RESULTS: The central corneal
      swelling at postoperative day 1 was strongly correlated with the central corneal
      endothelial cell loss at 3 months (R(2) = 0.785, P < .001). CONCLUSIONS: In this
      series, with large variations in the corneal swelling at the first postoperative
      day, the degree of permanent corneal endothelial damage was reflected in the
      degree of early postoperative corneal swelling. Measuring the difference in
      pachymetry at postoperative day 1 is a useful way to assess the effects on the
      corneal endothelium exerted by the phacoemulsification procedure.

PMID- 15953434
TI  - Central visual function and the NEI-VFQ-25 near and distance activities subscale
      scores in people with type 1 and 2 diabetes.
AB  - PURPOSE: To investigate relationships between clinical measures of central visual
      function and NEI-VFQ-25 Near and Distance Activities subscales in patients with
      diabetic retinopathy. DESIGN: Clinic-based, cross-sectional, observational study.
      METHODS: The NEI-VFQ-25 was administered to 170 people with type 1 or 2 diabetes
      before an ocular examination that included visual acuity, contrast sensitivity,
      and central visual fields. Multiple linear regression and exact multiple logistic
      regression were used to assess the relationship between poor acuity (<69
      letters), poor contrast sensitivity (<1.5 log units), and abnormal visual fields
      (mean deviation < or = -5dB) and NEI-VFQ-25 subscale scores. RESULTS: Final
      multivariable linear models explained a beta = 4.7 letter difference (P < or =
      .001) for each 25-point Near Activities subscale score difference. Similar
      effects were observed for the Distance Activities subscale, although the
      magnitudes of regression and partial correlation coefficients were lower (beta =
      3.3 letters, P < or = .01). Final logistic regression models on abnormal clinical
      categories of central visual function demonstrated relationships only with the
      Near Activities subscale. For a 1-point change in Near Activities subscale score,
      the odds of obtaining a poor score for visual acuity, central visual fields, and
      contrast sensitivity changed by 0.08 (P < or = .001), 0.07 (P < or = .05), and
      0.12 (P < or = .001), respectively. CONCLUSIONS: NEI-VFQ-25 Near and Distance
      Activities subscales demonstrate utility as measures of central visual function
      in persons with type 1 or 2 diabetes. Low scores on the NEI-VFQ-25 may reflect
      poor central visual fields and contrast sensitivity in addition to poor visual
      acuity.

PMID- 15953435
TI  - Outcome of external dacryocystorhinostomy combined with membranectomy of a distal
      canalicular obstruction.
AB  - PURPOSE: To investigate the accuracy of the preoperative evaluation in
      identifying a membranous obstruction of the distal canaliculus and the success
      rate of an external dacryocystorhinostomy (DCR) when membranectomy of the
      canalicular obstruction is also performed. DESIGN: Retrospective, interventional
      case series. METHODS: The surgical records of the lacrimal cases operated at
      Moorfields Eye Hospital between January 1997 and December 1999 were reviewed. All
      the patients with evidence of a membranous block of the canalicular opening into
      the sac identified and excised during the course of a standard DCR procedure with
      silastic intubation and a minimum follow-up period of 12 months were selected for
      this study. The records were analyzed for preoperative evaluation with syringing
      and probing, surgical details, outcome, and complications. RESULTS: In 59 (85%)
      cases a functional anastomosis was established after tube removal. Additionally,
      5 cases (7%) had patent system but required later ectropion repair and considered
      successful. Only 4 (6%) patients needed further lacrimal surgery, and one was
      referred to the ENT department for nasal polyps. The silastic tube was removed at
      a mean period of 6 weeks (SD = 4; range, 2-24 weeks), and the mean follow-up
      period was 13 months (SD = 3; range, 12-29 months). The preoperative evaluation
      failed to identify the membranous obstruction in 30 (43%) cases, which were
      correctly diagnosed intraoperatively. CONCLUSIONS: In our series the anatomic
      success rate of 92% after DCR with membranectomy is comparable to the outcome of
      the DCR procedure. The distal canalicular membranous obstruction is an anatomic
      factor that may lead to surgical failure if not identified and excised.

PMID- 15953436
TI  - Quantitative thickness measurement of retinal layers imaged by optical coherence
      tomography.
AB  - PURPOSE: To report an image analysis algorithm that was developed to provide
      quantitative thickness measurement of retinal layers on optical coherence
      tomography (OCT) images. DESIGN: Prospective cross-sectional study. METHODS:
      Imaging was performed with an OCT3 commercial instrument in 10 visually normal
      healthy subjects. A dedicated software algorithm was developed to process the raw
      OCT images and detect the depth location of peaks from intensity profiles.
      Quantitative thickness measurements of three retinal layers, in addition to total
      retinal thickness, were derived. Total retinal thickness measurements obtained by
      the algorithm were compared with measurements provided by the standard OCT3
      software. RESULTS: The total retinal thickness profile demonstrated foveal
      depression, corresponding to normal anatomy, with a thickness range of 160 to 291
      microm. Retinal thickness measured by the algorithm and by the standard OCT3
      software were highly correlated (R = 0.98). The inner retinal thickness profile
      predictably demonstrated a minimum thickness at the fovea, ranging between 58 to
      217 microm along the 6-mm scan. The outer retinal thickness profile displayed a
      maximum thickness at the fovea, ranging between 66 to 107 microm along the 6-mm
      scan. The photoreceptor outer segment thickness profile was relatively constant
      along the 6-mm scan through the fovea, ranging between 42 to 50 microm. The
      intrasubject variabilities of the inner retina, outer retina, and photoreceptor
      outer segment thickness was 14, 10, and 6 microm, respectively. CONCLUSIONS:
      Thickness measurements of retinal layers derived from OCT images have potential
      value for objectively documenting disease-related retinal thickness abnormalities
      and monitoring progressive changes over time.

PMID- 15953437
TI  - The rate of visual field loss in optic nerve head drusen.
AB  - PURPOSE: To define the rate of visual field loss in patients with optic nerve
      head drusen (ONHD). DESIGN: Retrospective chart review. METHODS: Goldmann visual
      field (GVF) testing from initial visit and last follow-up examination were
      quantified using the modified Esterman grid technique. The rate of visual field
      loss was calculated by comparing the initial GVF to the last follow-up GVF. A
      comparative analysis of GVF and age at initial evaluation was performed on all
      patients with an initial GVF only. SETTING: Tertiary academic care center.
      PARTICIPANTS: Inclusion criteria for the rate analysis: (1) diagnosis of ONHD and
      (2) at least 36 months of follow-up with serial GVF testing. EXCLUSION CRITERIA:
      (1) patients with glaucoma or glaucoma-suspect; (2) history or examination
      evidence for other ocular disease; and (3) drusen-related macular causes of
      visual loss. RESULTS: Thirty-two of 292 charts were included in the rate
      analysis. The rate of visual field loss was 1.58%. There was no statistically
      significant difference between men and women (P = .74). One hundred eighty
      patients were included in the initial visual field analysis. There was a
      significant negative correlation between age and GVF, with older patients having
      lower GVF scores with a Spearman correlation of -0.42 (P < 0.0001); 73% of these
      180 patients had mild, minimal, or no visual field loss. CONCLUSIONS: The rate of
      visual field loss for ONHD over a 36-month interval of time was 1.6% per year.
      Patients with minimal or no visual field loss were younger, and patients with
      moderate or severe visual loss were older.

PMID- 15953438
TI  - Clinical characteristics and surgical outcomes of pediatric rhegmatogenous
      retinal detachment in Taiwan.
AB  - PURPOSE: To evaluate the clinical features and surgical and visual outcomes of
      rhegmatogenous retinal detachment (RRD) in the pediatric population. DESIGN:
      Retrospective, noncomparative, interventional case series. METHODS: A review of
      patients under 18 years who underwent primary retinal detachment surgery at
      National Taiwan University Hospital from 1989 to 2003 was conducted. RESULTS:
      Included in the study were 152 eyes of 146 patients (mean age of 13.1 years).
      Male patients comprised 69.9% of the sample. Bilateral RRD was present in 4.1%.
      Etiologies included myopia >4 diopters (37.5%), trauma (32.9%), developmental
      anomaly (11.8%), previous surgery (5.9%), previous uveitis (3.9%), atopic
      dermatitis (2.6%), and unknown (5.3%). Macular detachment was found in 73.0%. The
      most common primary treatment was scleral buckling (61.2%). Single-operation
      reattachment was accomplished in 58.5% of patients and eventual reattachment in
      78.3% of patients occurring in a mean of 1.5 (SD = 0.9) operations. Average
      postoperative follow-up time was 48.3 months. Visual improvement occurred in
      42.8%, remained the same in 32.2%, and worsened in 19.1%. In the logistic
      regression model, statistically significant risk factors for poor surgical
      outcome were nonmyopic RRD (P = .026), macular involvement (P = .01), and
      presence of proliferative vitreoretinopathy (P = .07). CONCLUSIONS: Myopia >4
      diopters was the most common etiology in retinal detachment in our sample,
      followed by trauma. Myopia (> -4.0 diopters) may be more common than previously
      reported. Most eyes (78.3%) were anatomically reattached after multiple
      surgeries. Retinal detachment not associated with myopia is a newly identified
      predictor for poor surgical outcomes.

PMID- 15953439
TI  - Intereye difference in exudative age-related macular degeneration with minimally
      classic or occult subfoveal neovascularization after unilateral intravitreal
      injection of triamcinolone acetonide.
AB  - PURPOSE: To report on visual outcome after intravitreal injection of
      triamcinolone acetonide for exudative age-related macular degeneration. DESIGN:
      Interventional comparative non-randomized clinical trial. METHODS:  SETTING:
      Institutional. PATIENTS: Twenty consecutive patients with bilateral exudative age
      related macular degeneration with minimally classic or occult subfoveal
      neovascularisation. INTERVENTIONS: Unilateral intravitreal injection of about 20
      mg triamcinolone acetonide into the eye (study group) more severely affected or
      showing more pronounced progression of the disease. Mean follow-up was 13.5 +/-
      4.1 months. MAIN OUTCOME MEASURES: Visual acuity. RESULTS: In the study group,
      visual acuity increased significantly (P < 0.001) from 0.96 +/- 0.32 logMar to a
      mean maximum of 0.76 +/- 0.30 logMar during follow-up. An increase in best visual
      acuity during follow-up was found in 18 (90%) eyes. In 11 (55%) eyes and 7 (35%)
      eyes, respectively, best visual acuity increased by at least two Snellen lines
      and three Snellen lines, respectively. In the control group, visual acuity at
      baseline and the highest visual acuity measurements during follow-up did not vary
      significantly (P = 0.90). Comparing study group and control group, visual acuity
      gain was significantly (P = 0.003) higher in the study group. Correspondingly,
      the number of eyes with an increase in visual acuity (P = 0.002) and with an
      increase in visual acuity higher > or = 3 lines compared to a loss of > or = 3
      lines was significantly (P = 0.027) higher in the study group. CONCLUSIONS:
      Intravitreal triamcinolone acetonide may temporarily increase visual acuity in
      eyes with exudative age-related macular degeneration.

PMID- 15953440
TI  - Comparative study of two sets of criteria for the diagnosis of Vogt-Koyanagi
      Harada's disease.
AB  - PURPOSE: The Vogt-Koyanagi-Harada's (VKH) Disease Committee established the
      "Revised diagnostic criteria for VKH disease" in 2001. The purpose of the present
      study was to assess the concordance between these criteria and the traditional
      Sugiura's diagnosis system. DESIGN: Observational case series. METHODS: The
      medical records of patients previously diagnosed with VKH disease based upon
      Sugiura's criteria at the Uveitis Survey Clinic of the Hokkaido University
      Hospital between 1991 and 2003 were retrospectively reevaluated using the VKH
      Committee's revised diagnostic criteria for VKH disease. RESULTS: Sugiura's
      criteria were used to identify 169 patients with VKH disease. All patients were
      Japanese, and 95 cases (56%) were women. Mean age at the time of their first
      visit to our clinic was 44.7 +/- 13.9 years (range, 9 to 74 years). Using the VKH
      Committee's new criteria, 91.7% of the previously diagnosed VKH patients were
      classified as having the disease. Of this group, 11.8% were classified as
      complete, 71% incomplete, and 8.9% as probable VKH disease. CONCLUSIONS: The VKH
      Committee's revised diagnostic criteria proved useful for VKH disease diagnosis,
      as the concordance rate for the two criteria was more than 90%. However, patients
      who had prior cataract surgery or who lacked signs of serous retinal detachment
      were not classified as having VKH disease because of exclusion by the VKH
      Committee's new criteria.

PMID- 15953441
TI  - Celecoxib, a selective inhibitor of cyclooxygenase 2 for therapy of diffuse
      anterior scleritis.
AB  - PURPOSE: Scleritis is a painful inflammation of the sclera that is often
      difficult to treat. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have been
      shown to be effective. Results of treating 24 cases of diffuse anterior scleritis
      with the novel selective COX-2 inhibitor celecoxib are reported. DESIGN:
      Nonrandomized prospective study. METHODS: Twenty-four patients suffering from
      diffuse anterior scleritis were seen in the Interdisciplinary Uveitis Center in
      Heidelberg between April 2001 and April 2003. All patients were treated with a
      200- to-800 mg dose of celecoxib per day, in divided doses, depending on the
      degree of discomfort and clinical severity. RESULTS: Twenty-two patients
      experienced significant clinical improvement within an average of 5 days of
      starting celecoxib. These patients reported a complete loss of pain and scleral
      redness. As they experienced complete symptomatic remission, the dose of
      celecoxib was tapered. Three of these patients suffered from a second attack of
      scleritis, with one patient requiring long-term low-dose therapy, one patient
      showing a nodular form, and the third showing no improvement. Treatment with
      celecoxib was associated with no side effects apart from allergic exanthema in
      two patients. CONCLUSION: Due to its anti-inflammatory potency and low rate of
      side effects, celecoxib is an effective drug for the treatment of diffuse
      anterior scleritis. Compared with other NSAIDs it shows minimal gastrointestinal
      side effects, so its high cost is justified. It represents an alternative drug
      therapy before systemic immunosuppressive treatment.

PMID- 15953442
TI  - Is there a role for neurotrophin treatment of the ocular surface following laser
      in situ keratomileusis (LASIK)?

PMID- 15953443
TI  - Steroids for branch retinal vein occlusion.

PMID- 15953444
TI  - Reducing endophthalmitis risk factors: where we stand.

PMID- 15953445
TI  - Progression of the optic disk as a reference standard in glaucoma.

PMID- 15953446
TI  - Evolving management of optic neuritis and multiple sclerosis.
AB  - PURPOSE: To review the relation of optic neuritis to multiple sclerosis (MS) and
      the indications, modalities, and results of therapy for optic neuritis, for both
      visual and general neurologic function. DESIGN: Literature review and author's
      experience. METHODS: Analysis of both laboratory and clinical evidence supporting
      the use of corticosteroids, immunomodulation agents, and other modalities in the
      treatment of optic neuritis and MS. RESULTS: Although treatment of optic neuritis
      with corticosteroids may hasten visual recovery to a minor degree, it has no long
      term beneficial effect on visual outcome. Optic neuritis is frequently the
      initial manifestation of multiple sclerosis. The risk of later development of
      clinically definite MS (CDMS) correlates with white matter demyelinative lesions
      on magnetic resonance imaging (MRI). The role of corticosteroid therapy alone in
      reducing the risk of subsequent MS is unclear, but recent studies suggest that
      the combination of immunomodulation agents (IMAs) and corticosteroids
      significantly reduces the later development of MS. Current research indicates
      that, contrary to previous doctrine, axonal damage is an early finding in MS.
      CONCLUSIONS: The risk of MS after optic neuritis may be predicted. The use of
      corticosteroids and IMAs, particularly in those at substantial risk, reduces the
      frequency and severity of developing CDMS. Earlier, more aggressive therapy in
      optic neuritis may be proven to reduce permanent axonal injury and progressive
      disability in MS.

PMID- 15953447
TI  - Combined esterified estrogen and methyltestosterone treatment for dry eye
      syndrome in postmenopausal women.
AB  - PURPOSE: To determine whether systemic replacement with combined esterified
      estrogen (EE) and methyltestosterone (MT) (EE + MT) would reduce symptoms and
      promote clinical improvement in postmenopausal women with dry eye syndrome (DES).
      DESIGN: Retrospective, noncomparative, interventional case series. METHODS:
      Investigators reviewed the charts of 11 postmenopausal women treated within the
      last 3 years with EE + MT. RESULTS: The mean patient age was 65.2 years (standard
      deviation [SD] 11.4, range 48-84 years). The mean treatment duration was 12.2
      months (SD 6.2 months, range 4-24 months). Ten (91%) of 11 patients reported
      improvement in dry eye symptoms while receiving treatment. For these 10, relief
      occurred after an average of 4.1 months of treatment (SD 3.2, range, 1-9 months).
      CONCLUSIONS: Treatment with EE + MT may be efficacious for DES of various
      etiologies. A randomized placebo-controlled trial is planned to further evaluate
      these encouraging findings.

PMID- 15953448
TI  - Selective laser trabeculoplasty (SLT) complicated by intraocular pressure
      elevation in eyes with heavily pigmented trabecular meshworks.
AB  - PURPOSE: To report and assess the complication of intraocular pressure (IOP)
      elevations after selective laser trabeculoplasty (SLT) in patients with heavily
      pigmented trabecular meshworks. DESIGN: Noncomparative, observational case
      series. METHODS: Retrospective analysis of the medical files of four glaucoma
      patients with heavily pigmented trabecular meshwork, who presented with IOP
      elevations after SLT. RESULTS: All four glaucoma patients presented with post-SLT
      IOP elevations. Three had features of pigmentary dispersion syndrome, and the
      fourth had a heavily pigmented trabecular meshwork. Two patients had previous
      argon laser trabeculoplasty (ALT) in the same eye in which SLT was performed, and
      one had a previous ocular trauma. Eventually, three of the patients required
      surgical trabeculectomy. CONCLUSIONS: This case series suggests that post-SLT IOP
      elevations can be a serious adverse event in some glaucomatous patients. It is
      recommended by the authors that patients with a deeply pigmented trabecular
      meshwork, taking multiple topical medications and having previous ALT treatment,
      should be considered at higher risk for this complication.

PMID- 15953449
TI  - Total blindness from presumed optic nerve melanocytoma.
AB  - PURPOSE: To describe total blindness secondary to presumed optic nerve
      melanocytoma. DESIGN: Interventional case report. METHODS: A 12-year-old African
      American girl, who developed loss of light perception secondary to a pigmented
      lesion of the optic disk, underwent transvitreal fine-needle aspiration biopsy
      (FNAB) of the lesion. RESULTS: Cytopathology revealed cells with features of
      melanocytoma and melanophages but no cells compatible with melanoma. The patient
      is being followed without treatment. CONCLUSIONS: Optic nerve melanocytoma can
      cause total blindness in the affected eye. Although it has limitations, FNAB can
      assist in diagnosis and management of melanocytoma with visual loss.

PMID- 15953451
TI  - Intravitreal triamcinolone acetonide for choroidal granuloma in sarcoidosis.
AB  - PURPOSE: To report the clinical course of intravitreal triamcinolone acetonide on
      choroidal granuloma secondary to sarcoidosis that was refractory to systemic
      prednisolone DESIGN: Interventional case report. METHODS: A 29-year-old Chinese
      man with sarcoidosis presented with isolated posterior segment involvement in his
      left eye as retinal periphlebitis, retinal granulomas, and choroidal granuloma.
      Retinal periphlebitis and retinal granulomas responded well to oral
      corticosteroid but not the choroidal granuloma. It gradually grew in size and
      caused a drop in left-eye vision to 20/70. Intravitreal triamcinolone acetonide
      (4 mg) was injected three times in total. RESULTS: The choroidal mass began to
      shrink in size after the second injection and completely regressed after the
      third. The choroidal granuloma became a scar, with no angiographic leakage. The
      patient's visual acuity improved and remained stable at 20/40 at the last follow
      up, 6 months after the last injection. CONCLUSIONS: Given the encouraging
      results, further study on intravitreal triamcinolone acetonide for macular and
      peripapillary choroidal granulomas secondary to systemic sarcoidosis is
      warranted.

PMID- 15953450
TI  - Linezolid-induced optic neuropathy.
AB  - PURPOSE: To report a case of optic neuropathy associated with prolonged use of a
      new antibiotic, linezolid. DESIGN: Interventional case report. METHODS: Optic and
      peripheral neuropathy occurred in a 27-year-old woman who was undergoing
      prolonged linezolid therapy for osteomyelitis. The use of corticosteroid
      exacerbated visual loss. Discontinuation of the linezolid therapy resulted in
      marked improvement of optic neuropathy. RESULTS: Linezolid-induced optic
      neuropathy was diagnosed in this case, because prolonged linezolid therapy was
      performed at a higher dose than usual and because the patient recovered after
      linezolid therapy was discontinued. CONCLUSIONS: With prolonged linezolid
      therapy, ophthalmologists should be aware that bilateral optic neuropathy can
      occur and that corticosteroids are not indicated for this neuropathy.

PMID- 15953452
TI  - Different mutations in carbohydrate sulfotransferase 6 (CHST6) gene cause macular
      corneal dystrophy types I and II in a single sibship.
AB  - PURPOSE: The aim of this study was to examine the carbohydrate sulfotransferase 6
      (CHST6) gene for mutations in a sibship with both macular corneal dystrophy (MCD)
      types I and II. DESIGN: Clinically relevant laboratory investigation. METHODS:
      The coding region of the CHST6 gene was examined for mutations. RESULTS: In one
      sibling, MCD type I was due to a homozygous C1110T (Arg140end) mutation in CHST6.
      Two MCD type II individuals exhibited three heterozygous nucleotide changes:
      C1110T, G1360A (Gly223Asp), and G1685T (Gln331His). Analysis of the upstream
      region was performed on one individual with MCD type II, and no upstream deletion
      or substitution was found. CONCLUSIONS: These findings fit the haplotype analysis
      that we reported previously and indicate that the predicted protein that is
      encoded by CHST6 is more severely affected in the individual with MCD type I than
      in the siblings with MCD type II.

PMID- 15953453
TI  - A new method for comprehensive bird's-eye analysis of the surgically excised
      internal limiting membrane.
AB  - PURPOSE: To investigate the role of cells and extracellular matrix on the
      internal limiting membrane (ILM), we demonstrated a new method for a
      comprehensive bird's-eye analysis of surgically excised ILM. DESIGN: Laboratory
      investigation. METHODS: The ILM of an idiopathic epiretinal membrane was fixed
      and spread out onto a glass slide, using fine needles under a biomicroscope. The
      expanded ILM was analyzed by light microscopy, immunohistochemistry, and scanning
      electron microscopy. RESULTS: The excised ILM could be unfolded and spread out as
      a flat sheet onto the glass slide. Immunohistochemistry revealed that most
      migrating cells were glial cells. Scanning electronmicroscopy revealed that the
      vitreous surface of the ILM was smooth, in contrast to the rough retinal surface.
      The ILM showed abundant cellular migration as a continuous stratified cellular
      sheet. CONCLUSIONS: This new bird's-eye-view observation of excised ILM enables
      us to carry out comprehensive analysis of cellular distribution from a temporal
      and spatial perspective.

PMID- 15953454
TI  - Multiple elements in the deposits of opacified Hydroview intraocular lens.
AB  - PURPOSE: To report the ultrastructural and elemental features of two opacified
      intraocular lenses (IOLs). DESIGN: Histopathologic case series. METHODS: Two
      opaque hydrophilic acrylic IOLs (Hydroview H60M, Bausch & Lomb Surgical
      Clearwater, Florida, USA) explanted from two Chinese patients in Taiwan. The
      explanted IOLs were evaluated by light microscopy, scanning electron microscopy,
      and energy-dispersive x-ray spectroscopy. RESULTS: Brownish granular and
      scattered crystal-like deposits were found in case 2, whereas only fine white
      granular deposits were found in case 1. Using EDX spectroscopy, the elements of
      deposits on IOL optics were calcium and phosphorus in case 1, but in case 2,
      fluorine, magnesium, and sodium were demonstrated in addition to calcium and
      phosphorus. CONCLUSIONS: Our study indicated a difference in morphology and
      elements of deposits on opaque IOL optics between these two cases. It was
      suggested that multiple elements may contribute to the formation of deposits.

PMID- 15953455
TI  - The Q368STOP myocilin mutation in a population-based cohort: the Blue Mountains
      Eye Study.
AB  - PURPOSE: To investigate the prevalence of the Q368STOP myocilin mutation in a
      population-based cohort: the Blue Mountains Eye Study (BMES). DESIGN: Population
      based study. METHODS: DNA was extracted from 2,142 individuals collected through
      the BMES, including 31 individuals with glaucoma. All individuals were screened
      for the presence of the Q368STOP mutation of myocilin. Genotyping of the
      microsatellite markers My5, My3, D1S2815, and D1S1619 was also undertaken.
      RESULTS: None of the 31 open-angle glaucoma-positive individuals presented with
      the Q368STOP mutation. However, two individuals (aged 56 and 72) with no clinical
      signs of OAG, were identified with this mutation. Allele sharing at the four
      microsatellite markers defining the Q368STOP disease haplotype for OAG was found
      in these two individuals. CONCLUSIONS: The Q368STOP myocilin mutation occurs at a
      low prevalence (0.09%) in a general, older population.

PMID- 15953456
TI  - Pterygium, pinguecula, and 5-year incidence of cataract.
AB  - PURPOSE: To assess longitudinal associations between pterygium, pinguecula, and 5
      year incident cataract. DESIGN: Population-based cohort study. METHODS: The Blue
      Mountains Eye Study examined 3,654 residents aged > or =49 years during 1992 to
      1994 and reexamined 2,335 (75.1% of survivors) 5 years later. Slit-lamp
      examination recorded pterygium and pinguecula. Cataract was assessed using masked
      grading of lens photographs. Incidence was assessed in participants without
      cataract at baseline. Eye-specific data were analyzed using generalized
      estimating equation models, adjusting for age, sex, smoking, diabetes, and
      corticosteroid use. RESULTS: Pinguecula was associated with a borderline
      significant, increased risk of developing cortical cataract (adjusted odds ratio,
      1.3; 95% confidence interval, 1.0 to 1.7). We found no significant association
      between baseline pterygium and the incidence of cortical, nuclear, or posterior
      subcapsular cataract. CONCLUSIONS: Longitudinal data from the same study
      population provide weak support for cross-sectional associations between
      pinguecula and cortical cataract previously reported from our study.

PMID- 15953457
TI  - Isolated optic nerve lymphoma diagnosed by optic nerve biopsy.
AB  - PURPOSE: To report a case of isolated optic nerve lymphoma diagnosed by optic
      nerve biopsy. DESIGN: Case report. METHODS: A 66-year-old woman was referred to
      the Neuro-Ophthalmology Service because of a decrease in visual acuity and right
      optic disk edema. RESULTS: A magnetic resonance image of the brain showed only
      enhancement of the optic nerve. An examination that included ANA, c-ANCA, p-ANCA,
      Lyme titers, FTA-ABS, ACE level, chest x-ray, and lumbar puncture was negative.
      Because of rapid progression on clinical examination and serial imaging, an optic
      nerve biopsy was performed, which showed B-cell lymphoma. CONCLUSION: Optic nerve
      lymphoma can be confused with a variety of inflammatory and neoplastic
      infiltrations of the optic nerve on clinical and radiographic examinations. Optic
      nerve biopsy can be valuable in diagnosing isolated optic nerve lymphoma if other
      diagnostic tests are unrevealing, but the procedure carries considerable risk of
      loss of visual acuity and should be recommended judiciously.

PMID- 15953458
TI  - A new non-trocar system for 25-gauge transconjunctival pars plana vitrectomy.
AB  - PURPOSE: To introduce a new non-trocar system for 25-gauge transconjunctival pars
      plana vitrectomy (PPV). DESIGN: Study of a new surgical instrument. METHODS: This
      new non-trocar system for 25-gauge transconjunctival PPV consists of a contact
      lens ring featuring four projections containing 1.0-mm diameter holes located 3.0
      mm from the ring edge, a wedge-shaped 25-gauge infusion cannula, and two plugs.
      RESULTS: The ring is fixed with 7-0 silk sutures at the 3- and 9-o'clock
      positions on the limbus. Using the 25-gauge needle, three conjunctival and
      scleral incisions (n = 3) are made at the projection holes located
      inferotemporally, superonasally, and superotemporally. No intra- or postoperative
      complications were encountered in 14 patients treated by this non-trocar 25-gauge
      transconjunctival PPV. CONCLUSION: Using the system introduced here, 25-gauge
      transconjunctival PPV can be performed without suturing sclerotomies and without
      intra- or postoperative complications.

PMID- 15953459
TI  - Novel mutation in RLBP1 gene in a Japanese patient with retinitis punctata
      albescens.
AB  - PURPOSE: To report a novel mutation in the RLBP1 gene and optical coherence
      tomographic findings in a Japanese patient with retinitis punctata albescens.
      DESIGN: Observational case report. METHODS: The RLBP1 gene was analyzed by direct
      genomic sequencing. A complete ophthalmologic examination was performed. RESULTS:
      Compound heterozygous mutations in the RLBP1 gene were identified in the patient.
      The mutations were a novel missense Arg103Trp mutation and a missense Arg234Trp
      mutation, the causative mutation of Bothnia dystrophy. The patient's fundi showed
      numerous white dots with diffuse retinal mottling and bilateral macular
      degeneration. Her visual function deteriorated progressively during 12-year
      follow-up. Optical coherence tomography demonstrated decreased retinal thickness,
      especially the photoreceptor layer. CONCLUSION: A novel mutation in RLBP1 gene
      was found in a Japanese patient with retinitis punctata albescens. Degenerative
      changes of the outer retina were detected by optical coherence tomography.

PMID- 15953460
TI  - Chronic recurrent varicella-zoster virus keratitis confirmed by polymerase chain
      reaction testing.
AB  - PURPOSE: To report a case of chronic recurrent varicella virus epithelial
      keratitis in a child. DESIGN: Case report. METHODS: Clinical examination and
      polymerase chain reaction analysis of corneal epithelium. RESULTS: A 10-year-old
      healthy child developed chronic recurrent varicella virus keratitis with
      pseudodendrites after recovering from systemic varicella. Analysis of the
      debrided pseudodendrites was repeatedly positive for VZV DNA and negative for HSV
      DNA. Treatment with oral acyclovir and topical corticosteroid drops was effective
      in eliminating the pseudodendrites; however, recurrences occurred once the
      medications were discontinued. CONCLUSIONS: Varicella virus epithelial keratitis
      in children can be a recurrent chronic condition requiring prolonged treatment.

PMID- 15953461
TI  - Single intraocular pressure measurements and diurnal intraocular pressure
      profiles.
AB  - PURPOSE: To evaluate the probability of a single intraocular pressure measurement
      to be the highest measurement within a diurnal intraocular pressure profile.
      DESIGN: Hospital-based clinical, observational study. METHODS: The study included
      3,025 day-and-night intraocular pressure profiles measured on 1,072 eyes of 547
      Caucasian glaucoma patients or glaucoma suspects. Applanation tonometry was
      performed at 7 am, noon, 5 pm, 9 pm, and midnight. RESULTS: Intraocular pressure
      measurements were highest at 7 am, noon, 5 pm, 9 pm, and midnight, respectively,
      in 20.4%, 17.8%, 21.3% 13.9%, and 26.7% of the profiles, respectively. The
      measurement taken at 7 am was significantly (P < .001) closest to the maximal
      value of the profile. CONCLUSIONS: Any single intraocular pressure measurement
      taken between 7 am and 9 pm has a higher than 75% chance to miss the highest
      point of a diurnal curve. Intraocular pressure may be measured at different times
      of the day to have the best chance of observing the maximal value.

PMID- 15953462
TI  - Uveitis-associated flap edema and lamellar interface fluid collection after
      LASIK.
AB  - PURPOSE: To report two cases of corneal pathology associated with anterior
      uveitis after laser in situ keratomileusis (LASIK). DESIGN: Observational case
      report. METHODS: A 47-year-old man and a 50-year-old woman who experienced vision
      loss and corneal changes associated with acute anterior uveitis after LASIK were
      examined. RESULTS: The 47-year-old man, who had undergone LASIK for low myopia
      developed an interlamellar fluid pocket at the level of the flap interface,
      whereas the 50-year-old woman, who underwent LASIK for hyperopia, developed
      marked flap edema without interface fluid collection. CONCLUSIONS: These two
      cases demonstrated acute corneal fluid accumulation associated with episodes of
      acute anterior uveitis in eyes that had undergone LASIK. Uveitis should be
      considered a risk factor for vision threatening corneal complications after
      LASIK.

PMID- 15953463
TI  - Electrolysis for corneal opacities in a young patient with superficial variant of
      granular corneal dystrophy (Reis-Bucklers corneal dystrophy).
AB  - PURPOSE: To report the efficacy of electrolysis as a treatment of corneal
      opacities in a young patient with the superficial variant of granular corneal
      dystrophy. DESIGN: Interventional case report. METHODS: An 11-year-old boy
      presented with subepithelial opacities in both eyes. His visual acuity was 0.2 in
      the left eye; he received corneal electrolysis under topical anesthesia. RESULTS:
      The electrolysis, which required only 5 minutes, resulted in the disappearance of
      the subepithelial opacities. His visual acuity improved to 0.4 on the next day
      and was 1.0 eight months later. The corneal curvature and thickness were not
      altered by the electrolysis. CONCLUSIONS: Corneal electrolysis proved to be an
      effective treatment for subepithelial opacities, and we recommend electrolysis as
      an effective and simple treatment for young patients with SGCD.

PMID- 15953464
TI  - Solitary superficial angiomyxoma in the eyelid.
AB  - PURPOSE: To report the clinicopathologic features of a solitary superficial
      angiomyxoma arising in the eyelid. DESIGN: Case report. METHODS: A retrospective
      review of the clinical and pathologic features of a patient with solitary
      superficial angiomyxoma in the eyelid. RESULTS: A 47-year-old male presented with
      a right upper lid mass for 6 months. Excisional biopsy was performed, and
      microscopic examination revealed a tumor comprising loose spindle or stellate
      shaped cells in myxoid stroma sprinkled with small numbers of neutrophils. The
      tumor cells were negative for smooth muscle actin, desmin, S-100 protein, and
      CD34 on immunostaining. CONCLUSIONS: Ophthalmologists should be aware of
      superficial angiomyxoma as a rare cutaneous tumor with a tendency for local
      recurrence. Multiple lesions and occurrence in the external ear can be associated
      with the Carney's complex.

PMID- 15953465
TI  - Electrophysiological changes in lipaemia retinalis.
AB  - PURPOSE: To report the electrophysiologic findings in a patient with lipaemia
      retinalis. DESIGN: Observational case report. METHODS: An 11-year-old girl with
      diabetes had hyperlipidemia and presented for ophthalmologic consultation. Fundus
      examinations revealed milky discoloration of retinal vessels in both eyes.
      Laboratory testing disclosed hyperglycemia and markedly elevated level of
      triglycerides and cholesterol. Although the visual acuity was not affected, the
      electroretinograms showed decrease amplitudes of a- and b-wave in both cone and
      rod responses. RESULTS: After correction of blood sugar and lipids with insulin
      and diet control, the lipaemia retinalis resolved, and the impaired ERG response
      reversed within 1 week. CONCLUSIONS: Lipaemia retinalis usually resolves rapidly
      without visual impairment after correction of hyperlipidemia. The reversible
      deficits of electroretinogram response in lipaemia retinalis are reported for the
      first time. High level of triglycerides or cholesterol or both may impair retinal
      function. The mechanism of an impaired electroretinogram remained speculative.

PMID- 15953467
TI  - Vitrectomy with or without arteriovenous adventitial sheathotomy for macular
      edema associated with branch retinal vein occlusion.

PMID- 15953469
TI  - Endophthalmitis caused by streptococcus pneumoniae.

PMID- 15953471
TI  - Central corneal thickness and measured IOP response to topical ocular hypotensive
      medication in the Ocular Hypertension Treatment Study.

PMID- 15953472
TI  - Photosystem I lacking the PSI-G subunit has a higher affinity for plastocyanin
      and is sensitive to photodamage.
AB  - PSI-G is an 11 kDa subunit of PSI in photosynthetic eukaryotes. Arabidopsis
      thaliana plants devoid of PSI-G have a decreased PSI content and an increased
      activity of NADP(+) photoreduction in vitro but otherwise no obvious phenotype.
      To investigate the biochemical basis for the increased activity, the kinetic
      parameters of the reaction between PSI and plastocyanin were determined. PSI-G
      clearly plays a role in the affinity for plastocyanin since the dissociation
      constant (K(D)) is only 12 muM in the absence of PSI-G compared to 32 muM for the
      wild type. On the physiological level, plants devoid of PSI-G have a more reduced
      Q(A). This indicates that the decreased PSI content is due to unstable PSI rather
      than an adaptation to the increased activity. In agreement with this indication
      of decreased stability, plants devoid of PSI-G were found to be more photo
      inhibited both at low temperature and after high light treatment. The decreased
      PSI stability was confirmed in vitro by measuring PSI activity after illumination
      of a thylakoid suspension which clearly showed a faster decrease in PSI activity
      in the thylakoids lacking PSI-G. Light response of the P700 redox state in vivo
      showed that in the absence of PSI-G, P700 is more reduced at low light
      intensities. We conclude that PSI-G is involved in the binding dynamics of
      plastocyanin to PSI and that PSI-G is important for the stability of the PSI
      complex.

PMID- 15953473
TI  - Quantitative mathematical expressions for accurate in vivo assessment of
      cytosolic [ADP] and DeltaG of ATP hydrolysis in the human brain and skeletal
      muscle.
AB  - Magnetic Resonance Spectroscopy affords the possibility of assessing in vivo the
      thermodynamic status of living tissues. The main thermodynamic variables relevant
      for the knowledge of the health of living tissues are: DeltaG of ATP hydrolysis
      and cytosolic [ADP], the latter as calculated from the apparent equilibrium
      constant of the creatine kinase reaction. In this study we assessed the
      stoichiometric equilibrium constant of the creatine kinase reaction by in vitro
      (31)P NMR measurements and computer calculations resulting to be: logK(CK)=8.00+/
      0.07 at T=310 K and ionic strength I=0.25 M. This value refers to the
      equilibrium: PCr(2-)+ADP(3-)+ H(+)=Cr+ATP(4-). We also assessed by computer
      calculation the stoichiometric equilibrium constant of ATP hydrolysis obtaining
      the value: logK(ATP-hyd)=-12.45 at T=310 K and ionic strength I=0.25 M, which
      refers to the equilibrium: ATP(4-)+H(2)O=ADP(3-)+PO(4)(3-)+2H(+). Finally, we
      formulated novel quantitative mathematical expressions of DeltaG of ATP
      hydrolysis and of the apparent equilibrium constant of the creatine kinase
      reaction as a function of total [PCr], pH and pMg, all quantities measurable by
      in vivo (31)P MRS. Our novel mathematical expressions allow the in vivo
      assessment of cytosolic [ADP] and DeltaG of ATP hydrolysis in the human brain and
      skeletal muscle taking into account pH and pMg changes occurring in living
      tissues both in physiological and pathological conditions.

PMID- 15953474
TI  - Species-specific modulation of the mitochondrial permeability transition by
      norbormide.
AB  - In the present study, we show that norbormide stimulates the opening of the
      permeability transition pore (PTP) in mitochondria from various organs of the rat
      but not of guinea pig and mouse. Norbormide does not affect the basic parameters
      that modulate the PTP activity since the proton electrochemical gradient,
      respiration, phosphorylation and Ca(2+) influx processes are only partially
      affected. On the other hand, norbormide induces rat-specific changes in the
      fluidity of the lipid interior of mitochondrial membranes, as revealed by
      fluorescence anisotropy of various reporter molecules. Such changes increase the
      PTP open probability through the internal Me(2+) regulatory site. The lack of PTP
      opening by norbormide is matched by a negligible perturbation of internal lipid
      domains in guinea pig and mouse, suggesting that the drug does not gain access to
      the matrix in the mitochondria from these species. Consistent with this
      interpretation, we demonstrate a preferential interaction of norbormide with the
      mitochondrial surface leading to alterations of the Me(2+) binding affinity for
      the external PTP regulatory site. Our findings indicate that norbormide affects
      Me(2+) binding to the regulatory sites of the PTP, and suggest that the drug
      could be taken up by a mitochondrial transport system unique to the rat. The
      characterization of the norbormide target may lead to a better understanding of
      the mechanisms underlying the mitochondrial PTP as well as to the identification
      of species-specific drugs that affect mitochondrial function.

PMID- 15953475
TI  - Entropy-assisted stacking of thylakoid membranes.
AB  - Chloroplasts in plants and some green algae contain a continuous thylakoid
      membrane system that is structurally differentiated into stacked granal membranes
      interconnected by unstacked thylakoids, the stromal lamellae. Experiments were
      conducted to test the hypothesis that the thermodynamic tendency to increase
      entropy in chloroplasts contributes to thylakoid stacking to form grana. We show
      that the addition of bovine serum albumin or dextran, two very different water
      soluble macromolecules, to a suspension of envelope-free chloroplasts with
      initially unstacked thylakoids induced thylakoid stacking. This novel restacking
      of thylakoids occurred spontaneously, accompanied by lateral segregation of PSII
      from PSI, thereby mimicking the natural situation. We suggest that such granal
      formation, induced by the macromolecules, is partly explained as a means of
      generating more volume for the diffusion of macromolecules in a crowded stromal
      environment, i.e., greater entropy overall. This mechanism may be relevant in
      vivo where the stroma has a very high concentration of enzymes of carbon
      metabolism, and where high metabolic fluxes are required.

PMID- 15953476
TI  - Interaction between subunit C (Vma5p) of the yeast vacuolar ATPase and the stalk
      of the C-depleted V(1) ATPase from Manduca sexta midgut.
AB  - Projection maps of a V(1)-Vma5p hybrid complex, composed of subunit C (Vma5p) of
      Saccharomyces cerevisiae V-ATPase and the C-depleted V(1) from Manduca sexta,
      were determined from single particle electron microscopy. V(1)-Vma5p consists of
      a headpiece and an elongated wedgelike stalk with a 2.1x3.0 nm protuberance and a
      9.5x7.5 globular domain, interpreted to include Vma5p. The interaction face of
      Vma5p in V(1) was explored by chemical modification experiments.

PMID- 15953477
TI  - Cellular energization protects the photosynthetic machinery against salt-induced
      inactivation in Synechococcus.
AB  - The effects of the energization of cells by light and by exogenous glucose on the
      salt-induced inactivation of the photosynthetic machinery were investigated in
      the cyanobacterium Synechococcus sp. PCC 7942. The incubation of the
      cyanobacterial cells in a medium supplemented with 0.5 M NaCl induced a rapid
      decline with a subsequent slow decline, in the oxygen-evolving activity of
      Photosystem (PS) II and in the electron-transport activity of PSI. Light and
      exogenous glucose each protected PSII and PSI against the second phase of the
      NaCl-induced inactivation. The protective effects of light and glucose were
      eliminated by an uncoupler of phosphorylation and by lincomycin, an inhibitor of
      protein synthesis. Light and glucose had similar effects on the NaCl-induced
      inactivation of Na(+)/H(+) antiporters. After photosynthetic and Na(+)/H(+)
      antiport activities had been eliminated by the exposure of cells to 0.5 M NaCl in
      the darkness, both activities were partially restored by light or exogenous
      glucose. This recovery was prevented by lincomycin. These observations suggest
      that cellular energization by either photosynthesis or respiration, which is
      necessary for protein synthesis, is important for the recovery of the
      photosynthetic machinery and Na(+)/H(+) antiporters from inactivation by a high
      level of NaCl.

PMID- 15953478
TI  - Extinction coefficients and critical solubilisation concentrations of
      photosystems I and II from Thermosynechococcus elongatus.
AB  - The absorption properties of chlorophyll a (Chla) in active core complexes of
      photosystems I (PSI) and II (PSII) isolated in high purity from the thermophilic
      cyanobacterium Thermosynechococcus elongatus were correlated with those of
      extracts in 80% acetone to determine effective extinction coefficients of protein
      bound Chla and molar extinction coefficients of core complexes and reaction
      centers (RC). These coefficients allow a quick determination of Chla and protein
      concentrations from steady-state absorption spectra of intact samples without the
      need for pigment extraction and protein destruction. In the visible range,
      epsilon(680)(p) = 57 mM(-1) cm(-1) for trimeric PSI (PSIt) and epsilon(674)(p) =
      70 mM(-1) cm(-1) for dimeric (PSIId) and monomeric (PSIIm) PSII (error +/-6%;
      superscript "p" refers to Chla bound to intact protein, subscripts are the peak
      maxima in nm). The integral extinction coefficient phi(p) = 2.8 nm microM(-1) cm(
      1) for the wavelength interval between 550 and 800 nm and the extinction
      coefficient epsilon(B)(p) = 14 mM(-1) cm(-1) for the smaller absorption maximum
      (B = 632 nm for PSI and 627 nm for PSII) were found to be essentially the same
      for both types of PS. The coefficients of PSIt are shown to remain unaltered when
      65% (v/v) of the buffer is replaced with glycerol. Molar extinction coefficients
      of core complexes were determined using Chla/RC ratios of 96+/-1 for PSI and 35+/
      2 for PSII based on X-ray data. In addition, the critical solubilisation
      concentration of n-dodecyl-beta-d-maltoside (betaDM), necessary to keep the core
      complexes in solution, was determined by turbidimetric titrations. It was found
      that at least approximately 500 betaDM molecules per PSIt ( approximately 2
      betaDM per Chla) and 190 betaDM molecules per PSIIm ( approximately 5 betaDM per
      Chla, also for PSIId) in excess of the critical micelle concentration of 0.16 +/-
      0.03 mM are necessary for a complete solubilisation of the core complexes.

PMID- 15953479
TI  - Overexpression and characterization of dark-operative protochlorophyllide
      reductase from Rhodobacter capsulatus.
AB  - Dark-operative protochlorophyllide oxidoreductase (DPOR) plays a crucial role in
      light-independent (bacterio)chlorophyll biosynthesis in most photosynthetic
      organisms. However, the biochemical properties of DPOR are still largely
      undefined. Here, we constructed an overexpression system of two separable
      components of DPOR, L-protein (BchL) and NB-protein (BchN-BchB), in the broad
      host-range vector pJRD215 in Rhodobacter capsulatus. We established a stable DPOR
      assay system by mixing crude extracts from the two transconjugants under
      anaerobic conditions. Using this assay system, we demonstrated some basic
      properties of DPOR. The Km value for protochlorophyllide was 10.6 muM. Ferredoxin
      functioned as an electron donor to DPOR. Elution profiles in gel filtration
      chromatography indicated that L-protein and NB-protein are a homodimer
      [(BchL)(2)] and a heterotetramer [(BchN)(2)(BchB)(2)], respectively. These
      results provide a framework for the characterization of these components in
      detail, and further support a nitrogenase model of DPOR.

PMID- 15953480
TI  - EPR study of electron transport in the cyanobacterium Synechocystis sp. PCC 6803:
      oxygen-dependent interrelations between photosynthetic and respiratory electron
      transport chains.
AB  - In this work, we investigated electron transport processes in the cyanobacterium
      Synechocystis sp. PCC 6803, with a special emphasis focused on oxygen-dependent
      interrelations between photosynthetic and respiratory electron transport chains.
      Redox transients of the photosystem I primary donor P700 and oxygen exchange
      processes were measured by the EPR method under the same experimental conditions.
      To discriminate between the factors controlling electron flow through
      photosynthetic and respiratory electron transport chains, we compared the P700
      redox transients and oxygen exchange processes in wild type cells and mutants
      with impaired photosystem II and terminal oxidases (CtaI, CydAB, CtaDEII). It was
      shown that the rates of electron flow through both photosynthetic and respiratory
      electron transport chains strongly depended on the transmembrane proton gradient
      and oxygen concentration in cell suspension. Electron transport through
      photosystem I was controlled by two main mechanisms: (i) oxygen-dependent
      acceleration of electron transfer from photosystem I to NADP(+), and (ii) slowing
      down of electron flow between photosystem II and photosystem I governed by the
      intrathylakoid pH. Inhibitor analysis of P700 redox transients led us to the
      conclusion that electron fluxes from dehydrogenases and from cyclic electron
      transport pathway comprise 20-30% of the total electron flux from the intersystem
      electron transport chain to P700(+).

PMID- 15953481
TI  - A cell-based model for the photoacclimation and CO(2)-acclimation of the
      photosynthetic apparatus.
AB  - We have developed a mathematical model based on the underlying mechanisms
      concerning the responses of the photosynthetic apparatus of a microalga cell
      which grows under constant incident light intensity and ambient CO(2)
      concentration. Photosynthesis involves light and carbon-fixation reactions which
      are mutually dependent and affect each other, but existing models for
      photosynthesis don't account for both reactions at once. Our modeling approach
      allows us to derive distinct equations for the rates of oxygen production, NADPH
      production, carbon dioxide fixation, carbohydrate production, and rejected
      energy, which are generally different. The production rates of the photosynthesis
      products are hyperbolic functions of light and CO(2) concentration. The model
      predicts that in the absence of photoinhibition, CO(2)-inhibition,
      photorespiration, and chlororespiration, a cell acclimated to high light and/or
      CO(2) concentration has higher photosynthetic capacity and lower photosynthetic
      efficiency than does a cell acclimated to low conditions. This results in
      crossing between the two curves which represent the oxygen production rates and
      carbon fixation rates in low and high conditions. Finally, in the absence of
      photoinhibition and CO(2)-inhibition, the model predicts the carbohydrate
      production rate in terms of both light intensity and CO(2) concentration.

PMID- 15953482
TI  - Through the looking glass: risk perception.

PMID- 15953483
TI  - Molecular and genetic approaches for behavioral analysis of protein function.
AB  - Behavioral neuroscientists traditionally have relied on pharmacological and
      lesion methods to explore the neural basis of complex behaviors. In the past
      decade, molecular and genetic approaches have been added to the repertoire, but
      their benefits are often severely constrained by a lack of temporal and spatial
      control over target protein modulation. Recent advances have allowed
      investigators to manipulate neuronal protein levels with far greater control over
      target selectivity, regional and cellular specificity, and duration of action
      than previously available. This article compares strengths and weaknesses in
      current molecular and genetic approaches for studying neuronal protein function
      in complex behaviors.

PMID- 15953484
TI  - The corticotropin-releasing hormone gene and behavioral inhibition in children at
      risk for panic disorder.
AB  - BACKGROUND: Behavioral inhibition to the unfamiliar (BI) is a heritable
      temperamental phenotype involving the tendency to display fearful, avoidant, or
      shy behavior in novel situations. BI is a familial and developmental risk factor
      for panic and phobic anxiety disorders. We previously observed an association
      between BI and a microsatellite marker linked to the corticotropin releasing
      hormone (CRH) gene in children at risk for panic disorder. To evaluate this
      further, we genotyped additional families for this marker and a panel of markers
      encompassing the CRH locus. METHODS: Sixty-two families that included parents
      with panic disorder and children who underwent laboratory-based behavioral
      observations were studied. Family-based association tests and haplotype analysis
      were used to evaluate the association between BI and polymorphisms spanning the
      CRH locus. RESULTS: We examined a set of markers which we found to reside in a
      block of strong linkage disequilibrium encompassing the CRH locus. The BI
      phenotype was associated with the microsatellite marker (p=.0016) and three
      single nucleotide polymorphisms (SNPs), including a SNP in the coding sequence of
      the gene (p=.023). Haplotype-specific tests revealed association with a haplotype
      comprising all of the markers (p=.015). CONCLUSIONS: These results suggest that
      the CRH gene influences inhibited temperament, a risk factor for panic and phobic
      anxiety disorders. Genetic studies of anxiety-related temperament represent an
      important strategy for identifying the genetic basis of anxiety disorders.

PMID- 15953485
TI  - Identification of multiple serine racemase (SRR) mRNA isoforms and genetic
      analyses of SRR and DAO in schizophrenia and D-serine levels.
AB  - BACKGROUND: We previously reported a reduction in serum levels of D-serine, an
      endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, in
      schizophrenia, supporting the hypofunction hypothesis of NMDA neurotransmission
      in schizophrenia. In this study, we examined the genetic roles of serine racemase
      (SRR), an enzyme catalyzing the formation of D-serine from L-serine, and D-amino
      acid oxidase (DAO) in the susceptibility to schizophrenia and the regulation of
      serum D-serine levels. METHODS: We determined the complete cDNA and genomic
      structures of SRR and performed mutation screening. Single nucleotide
      polymorphisms (SNPs) in SRR and DAO were tested for their association with
      schizophrenia in both case-control and family-based designs and for correlation
      with serum levels of D-serine. RESULTS: Genomic analyses revealed that human
      brain SRR transcripts consist of four isoforms with one major species, which were
      derived from alternative use of various 5' end exons. Genetic association
      analyses showed no significant association between SRR/DAO and schizophrenia. We
      replicated the decreased serum D-serine levels in schizophrenia in the sample
      set, but D-serine levels did not correlate with SRR/DAO genotypes. CONCLUSIONS:
      The SRR/DAO are not likely to be major genetic determinants in the development of
      schizophrenia or control of serum D-serine levels.

PMID- 15953486
TI  - P50 suppression in individuals at risk for schizophrenia: the convergence of
      clinical, familial, and vulnerability marker risk assessment.
AB  - BACKGROUND: Identification of individuals at risk for the development of
      schizophrenia is important because it can lead to a greater understanding of the
      early stages of the illness. The aim of the present study was to determine
      whether individuals "at risk" for schizophrenia have deficits in P50 suppression,
      a preattentive measure of sensory gating. METHODS: Thirty-one at-risk and 21
      normal comparison subjects were referred to the CARE (Cognitive Assessment and
      Risk Evaluation) Program at University of California San Diego. The primary aim
      of the CARE Program is to identify individuals who are at the greatest risk for
      conversion to psychosis, with a combination of clinical, familial, and
      vulnerability markers, including P50 suppression. RESULTS: As a group, the at
      risk subjects had modestly lower levels (effect size=.43) of P50 suppression
      (55.1%, SD=39.8) relative to comparison subjects (71.5%, SD=34.7). At-risk
      subjects with a first-degree relative with schizophrenia had profoundly deficient
      P50 suppression (16.4%, SD=33.8) compared with other at-risk (p<.05) and
      comparison subjects (p<.005). CONCLUSIONS: Ongoing longitudinal follow-up studies
      will determine whether it is possible to improve the predictive validity of the
      clinical and familial variables by using P50 suppression alone or in combination
      with other measures in determining which individuals are at greatest risk for
      schizophrenia.

PMID- 15953487
TI  - Serotonin transporter availability in patients with schizophrenia: a positron
      emission tomography imaging study with [11C]DASB.
AB  - BACKGROUND: Postmortem studies have reported several alterations in serotonin
      transporter (SERT) binding parameters in patients with schizophrenia. The aim of
      this study was to compare SERT availability in vivo in patients with
      schizophrenia and matched control subjects. METHODS: Ten medication-free patients
      with schizophrenia and 10 healthy subjects underwent positron emission tomography
      (PET) scans for 90 min after 11C-3-amino-4-(2
      dimethylaminomethylphenylthio)benzonitrile ([11C]DASB) injection. Metabolite
      corrected arterial input function was measured. Regional distribution volumes
      (mL/g) were derived with a two tissue compartment kinetic model. Outcome measures
      for SERT availability included binding potential (BP) and the specific-to
      nonspecific equilibrium partition coefficient (V3''). Ten brain regions with high
      density of SERT and where SERT availability can be reliably quantified with
      [11C]DASB were included in the analysis. RESULTS: No significant differences were
      observed in regional BP or V3'' between patients and control subjects. No
      significant relationships were observed between regional SERT availability and
      severity of positive, negative, and depressive symptoms. CONCLUSIONS: This study
      failed to detect alterations of SERT availability in patients with schizophrenia;
      however, this study does not rule out the possibility that schizophrenia might be
      associated with alterations of SERT density in the cortical regions, where the
      [11C]DASB-specific binding signal is too low for reliable quantification of SERT.

PMID- 15953488
TI  - Variation of human amygdala response during threatening stimuli as a function of
      5'HTTLPR genotype and personality style.
AB  - BACKGROUND: In the brain, processing of fearful stimuli engages the amygdala, and
      the variability of its activity is associated with genetic factors as well as
      with emotional salience. The objective of this study was to explore the relevance
      of personality style for variability of amygdala response. METHODS: We studied
      two groups (n=14 in each group) of healthy subjects categorized by contrasting
      cognitive styles with which they attribute salience to fearful stimuli: so-called
      phobic prone subjects who exaggerate potential environmental threat versus so
      called eating disorders prone subjects who tend to be much less centered around
      fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T
      during performance of a perceptual task of threatening stimuli and they were also
      matched for the genotype of the 5' variable number tandem repeat (VNTR)
      polymorphism in the serotonin transporter. RESULTS: The fMRI results indicated
      that phobic prone subjects selectively recruit the amygdala to a larger extent
      than eating disorders prone subjects. Activity in the amygdala was also
      independently predicted by personality style and genotype of the serotonin
      transporter. Moreover, brain activity during a working memory task did not
      differentiate the two groups. CONCLUSIONS: The results of the present study
      suggest that aspects of personality style are rooted in biological responses of
      the fear circuitry associated with processing of environmental information.

PMID- 15953489
TI  - Decreased prefrontal Myo-inositol in major depressive disorder.
AB  - BACKGROUND: Postmortem studies have shown robust prefrontal cortex glial losses
      and more subtle neuronal changes in major depressive disorder (MDD). Earlier
      proton magnetic resonance spectroscopy (1H-MRS) studies of the glial marker myo
      inositol in MDD were subject to potential confounds. The primary hypothesis of
      this study was that MDD patients would show reduced prefrontal/anterior cingulate
      cortex levels of myo-inositol. METHODS: Thirteen nonmedicated moderate-severe MDD
      patients and 13 matched control subjects were studied (six male, seven female per
      group). Proton magnetic resonance spectroscopy stimulated echo acquisition mode
      spectra (3.0 T; echo time=168 msec; mixing time=28 msec; repetition time=3000
      msec) were obtained from prefrontal/anterior cingulate cortex. Metabolite data
      were adjusted for tissue composition. RESULTS: Patients with MDD showed
      significantly lower myo-inositol/creatine ratios (.94+/-.23) than control
      subjects (1.32+/-.37) [F(1,23)=6.9; p=.016]. CONCLUSIONS: These data suggest a
      reduction of myo-inositol in prefrontal/anterior cingulate cortex in MDD, which
      could be a consequence of glial loss or altered glial metabolism. Additional in
      vivo studies of glial markers could add to the understanding of the
      pathophysiology of MDD.

PMID- 15953490
TI  - Are there differences in the symptoms that respond to a selective serotonin or
      norepinephrine reuptake inhibitor?
AB  - BACKGROUND: We examined two previously published studies comparing a
      norepinephrine (NE) selective agent, reboxetine, and a serotonin (5-HT) selective
      agent, fluoxetine, to determine if these agents have different effects on
      individual depressive symptoms. METHODS: Both studies were 8-week, double-blind,
      comparison studies of men and women with DSM III-R major depression. Within-group
      effect sizes for individual symptom change on the Hamilton Depression Rating
      Scale (HAMD) were determined in the observed case samples and in patients for
      whom the symptom was relatively severe at baseline. We required that any
      significant differences in one sample be cross-validated in the second. RESULTS:
      Two hundred fifty-three subjects in study I and 168 subjects in study II were
      randomized to reboxetine or fluoxetine. In both samples, depressed mood,
      decreased interest, and psychic anxiety had the greatest change. Effect sizes for
      all HAMD symptoms were similar for the two drugs. No difference between groups in
      one sample was replicated in the second. Among subjects with severe symptoms, no
      significant differences were cross-validated. CONCLUSIONS: Reboxetine and
      fluoxetine appear to have similar effects on depressive symptoms. These data
      suggest that NE and 5-HT selective antidepressant drugs act through the same
      final common pathway and challenge the belief that symptom differences are useful
      for antidepressant selection.

PMID- 15953491
TI  - Early-onset hypothesis of antipsychotic drug action: a hypothesis tested,
      confirmed and extended.
AB  - BACKGROUND: A recent meta-analysis rejected the "delayed onset of antipsychotic
      action hypothesis" that had been described in textbooks for decades. Since meta
      analyses are prone to a number of methodological problems, we attempted a
      replication by a) using a large database of individual patient data rather than
      meta-analysis, b) including another antipsychotic and c) extending the analysis
      from four weeks to one year. METHODS: We pooled the data of seven randomized
      trials involving amisulpride. The data included 1708 patients with schizophrenia
      and positive symptoms and we examined the incremental percentage Brief
      Psychiatric Rating Scale (BPRS) reduction over time. RESULTS: The "early onset of
      antipsychotic action hypothesis" was confirmed, as the reduction of overall and
      positive symptoms until week two was larger than the additional reduction until
      week four (p<.0001). Furthermore, in a subset with long-term data (n=748)
      approximately 68% of the mean BPRS change at one year was already achieved at
      four weeks in the observed cases. CONCLUSIONS: A substantial amount of the
      antipsychotic drug effect seems to occur during the first weeks of treatment.
      Subsequent analyses are needed to establish how long an antipsychotic should be
      tried before it is considered ineffective and alternative strategies implemented.

PMID- 15953492
TI  - Kappa opioid receptor activation disrupts prepulse inhibition of the acoustic
      startle in rats.
AB  - BACKGROUND: Compelling evidence indicates that kappa opioid receptor (KOR)
      agonists produce perceptual distortions in animals and humans, yet the mechanism
      of action and clinical relevance of such effects remain unclear. Since
      abnormalities in preattentional functions and informational processing are
      hypothesized to underlie psychotic disorders, the present study has been designed
      to assess the role of KOR on sensorimotor gating. METHODS: The effects of the
      selective KOR agonist U50488 were evaluated on the behavioral paradigm of
      prepulse inhibition (PPI) of the acoustic startle reflex (ASR). RESULTS: U50488
      (1.25, 2.5, and 5 mg/kg, subcutaneous [SC]) induced a dose-dependent reduction of
      PPI, which was efficiently prevented by the selective KOR antagonist
      norbinaltorphimine (nor-BNI, 10 mg/kg, SC), as well as by the atypical
      antipsychotic clozapine (5, 8 mg/kg, intraperitoneal [IP]) but not by the typical
      antipsychotic haloperidol (.1, .5 mg/kg, IP). Conversely, nor-BNI (10 mg/kg, SC)
      failed to reverse the PPI disruption mediated by both apomorphine (.25 mg/kg, SC)
      and dizocilpine (.1 mg/kg, SC). CONCLUSIONS: Our results support a pivotal role
      of KOR in the regulation of preattentional functions and sensorimotor gating,
      pointing to these receptors as a possible neurobiological substrate especially
      relevant to the clusters of psychosis unresponsive to typical antipsychotics.

PMID- 15953493
TI  - Fear potentiation and fear inhibition in a human fear-potentiated startle
      paradigm.
AB  - BACKGROUND: The inability to suppress excessive fear or anxiety is a significant
      clinical problem. In the laboratory, extinction is a preferred method for the
      study of fear inhibition; however, in this paradigm the same stimulus causes both
      elicitation (excitation) and inhibition of fear, making it difficult to know
      whether an experimental manipulation that affects extinction does so by affecting
      one or both of these processes. For this reason, we sought to develop a
      behavioral procedure in humans that would render a stimulus primarily inhibitory.
      METHODS: We adapted a conditional discrimination procedure (AX+/BX-), previously
      validated in animals, to a human fear-potentiated startle paradigm. Forty-one
      healthy volunteers were presented with one set of colored lights paired with the
      delivery of aversive airblasts to the throat (AX+) and a different series of
      lights presented without airblasts (BX-). RESULTS: Participants exhibited fear
      potentiation to AX+, discrimination between AX+ and BX-, and transfer of fear
      inhibition to A in an AB compound test but not in an AC compound test.
      CONCLUSIONS: We believe this procedure will advance clinical research on fear
      disorders, such as posttraumatic stress disorder and phobias, by providing an
      effective and relatively independent measure of fear potentiation and fear
      inhibition.

PMID- 15953494
TI  - Deep serotonergic and dopaminergic structures in fetal alcoholic syndrome: a
      study with nor-beta-CIT-single-photon emission computed tomography and magnetic
      resonance imaging volumetry.
AB  - BACKGROUND: In prenatally alcohol exposed children, the relationship between
      brain structure and function is highlighted to be important to study. METHODS: We
      studied 12 children with fetal alcoholic syndrome (FAS) and fetal alcoholic
      effects (FAE) by magnetic resonance imaging volumetry and by single-photon
      emission computed tomography with iodine-123 labeled 2beta-carbomethoxy-3beta-(4
      iodophenyl) ([123I]nor-beta-CIT) and related these findings to those from
      neuropsychological and psychiatric tests. RESULTS: The absolute volumes of
      studied nuclei, including the brain volume, were significantly smaller in FAS/FAE
      children than in control patients. After normalization of volumes, significant
      differences were not found. Left hippocampus was smaller than the right (p<.003)
      but did not significantly differ from the control subjects. The children with
      FAS/FAE showed reduced serotonin (p=.02) in the medial frontal cortex and
      slightly increased striatal dopamine transporter binding. All FAS/FAE children
      had attention-deficit/hyperkinetic disorder (ADHD). None had depression. The
      internalization scores correlated with dopamine transporter binding (r=-.65;
      p=.03). CONCLUSIONS: The results indicate that the serotonin (5-HT) system may be
      vulnerable to the effects of ethanol in utero. The high dopamine transporter
      levels may correlate with the ADHD findings. Reduced serotonin and increased
      binding of dopamine transporter are also seen in type 2 alcoholism. Some
      behavioral problems of FAS/FAE might be preventable by early intervention and
      treatment.

PMID- 15953495
TI  - Imaging brain mu-opioid receptors in abstinent cocaine users: time course and
      relation to cocaine craving.
AB  - BACKGROUND: Cocaine treatment upregulates brain mu-opioid receptors (mOR) in
      animals. Human data regarding this phenomenon are limited. We previously used
      positron emission tomography (PET) with [11C]-carfentanil to show increased mOR
      binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of
      abstinence. METHODS: Regional brain mOR binding potential (BP) was measured with
      [11C]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on
      a research ward and in 16 healthy control subjects. RESULTS: Mu-opioid receptor
      BP was increased in the frontal, anterior cingulate, and lateral temporal cortex
      after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first
      two regions after 1 week and in the anterior cingulate and anterior frontal
      cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was
      positively correlated with self-reported cocaine craving. Mu-opioid receptor BP
      was significantly correlated with percentage of days with cocaine use and amount
      of cocaine used per day of use during the 2 weeks before admission and with urine
      benzoylecgonine concentration at the first PET scan. CONCLUSIONS: These results
      suggest that chronic cocaine use influences endogenous opioid systems in the
      human brain and might explain mechanisms of cocaine craving and reinforcement.

PMID- 15953496
TI  - Abnormal sensitivity to cannabinoid receptor stimulation might contribute to
      altered gamma-aminobutyric acid transmission in the striatum of R6/2 Huntington's
      disease mice.
AB  - BACKGROUND: One of the earliest neurochemical alterations observed in both
      Huntington's disease (HD) patients and HD animal models is the dysregulation of
      the endocannabinoid system, an alteration that precedes the development of
      identifiable striatal neuropathology. How this alteration impacts striatal
      synaptic transmission is unknown. METHODS: We measured the effects of cannabinoid
      receptor stimulation on gamma-aminobutyric acid (GABA)-ergic synaptic currents
      recorded from striatal neurons of R6/2 HD mice in the early phase of their
      disease. RESULTS: The sensitivity of striatal GABA synapses to cannabinoid
      receptor stimulation is severely impaired in R6/2 HD mice. In particular, whereas
      in control animals activation of cannabinoid CB1 receptors results in a
      significant inhibition of both evoked and spontaneous GABA-mediated synaptic
      events by a presynaptic mechanism, in R6/2 mice this treatment fails to reduce
      GABA currents but causes, in contrast, a slight increase of spontaneous
      inhibitory postsynaptic currents (sIPSCs). CONCLUSIONS: Experimental HD was also
      associated with enhanced frequency of sIPSCs, a result consistent with the
      conclusion that loss of cannabinoid-mediated control of GABA transmission might
      contribute to hyperactivity of GABA synapses in the striatum of HD mice.
      Accordingly, spontaneous excitatory postsynaptic currents, which were not
      upregulated in R6/2 mice, were still sensitive to cannabinoid receptor
      stimulation.

PMID- 15953497
TI  - Alcoholism-associated hyperhomocysteinemia and previous withdrawal seizures.
AB  - BACKGROUND: Higher homocysteine levels were found in actively drinking alcoholics
      as well as in early abstinent patients. Furthermore, it has been shown that high
      homocysteine levels predicted first-onset alcohol withdrawal seizures. The aim of
      the present study was to determine plasma homocysteine levels in actively
      drinking alcoholics and patients with early abstinence in order to evaluate
      whether there is an additional association between elevated plasma homocysteine
      levels and a history of alcohol withdrawal seizures. METHODS: Two groups of
      patients with an established diagnosis of alcohol dependence were studied. Group
      A comprised 56 consecutively admitted alcoholics who had been abstinent from
      alcohol between 24 to 72 hours before hospitalization. Group B consisted of 144
      consecutively recruited alcoholics who were admitted - acutely intoxicated - for
      withdrawal treatment. Furthermore, groups were divided into two subgroups:
      patients with and without a history of alcohol withdrawal seizures. RESULTS:
      Alcoholics of GROUP B with a history of withdrawal seizures had significantly
      (p<.0001) higher homocysteine levels than actively drinking patients without
      seizures in their history: 42.0 micromol/l (SD 26.4) versus 22.5 micromol/l (SD
      11.4). Using a logistic regression analysis, history withdrawal seizures in Group
      B but not in Group A patients were best predicted by a high homocysteine level at
      admission (Wald chi2=15.5, p<.0001; odds ratio 1.11, 95% CI 1.05-1.20).
      CONCLUSIONS: Homocysteine levels on admission may be a useful screening method to
      identify actively drinking patients with a higher risk of alcohol withdrawal
      seizures.

PMID- 15953498
TI  - Celecoxib augmentation of continuously ill patients with schizophrenia.
AB  - BACKGROUND: Previous reports have demonstrated a beneficial effect of celecoxib
      adjunctive therapy for patients with an acute exacerbation of schizophrenia. We
      investigated the effects of celecoxib augmentation of atypical antipsychotic
      medications for continuously symptomatic outpatient subjects with schizophrenia
      to further extend these findings. We hypothesized that celecoxib augmentation
      therapy would improve psychopathology ratings compared with placebo. METHODS:
      Thirty-eight symptomatic outpatient subjects meeting DSM-IV criteria for
      schizophrenia and on a stable dose of an atypical antipsychotic medication for at
      least three months were randomized to receive 8 weeks of double blind placebo or
      celecoxib (400 mg/day) augmentation. Measures of psychopathology, functional
      disability, and extrapyramidal side effects were performed throughout the study.
      RESULTS: The treatment cohorts did not differ on any of the clinical outcome
      measures. CONCLUSIONS: Celecoxib augmentation of continuously ill outpatient
      subjects with schizophrenia did not improve clinical symptoms or measures of
      disability.

PMID- 15953499
TI  - Transcranial magnetic stimulation-evoked cortical inhibition: a consistent marker
      of attention-deficit/hyperactivity disorder scores in tourette syndrome.
AB  - BACKGROUND: Prior case-control studies using Transcranial Magnetic Stimulation
      (TMS) to probe the neural inhibitory circuitry of Attention Deficit Hyperactivity
      Disorder (ADHD), Tourette Syndrome (TS), and Obsessive Compulsive Disorder (OCD),
      have yielded conflicting results. Using regression analysis in TS patients with
      tics, ADHD, and/or OCD symptoms, all ranging from none to severe, we previously
      found that TMS-evoked short interval intracortical inhibition (SICI) correlated
      inversely with ADHD scores. We sought to validate this observation. METHODS: We
      used regression to estimate the consistency of the association between ADHD
      symptom scores and TMS-evoked SICI at two separate visits in 28 children and
      adults with TS. RESULTS: ADHD scores correlated significantly and consistently
      with SICI, particularly in patients not taking dopamine receptor blockers (r=.60
      and r=.58). Hyperactivity, not inattention, scores accounted for ADHD-related
      variance in SICI. CONCLUSIONS: SICI reliably reflects the severity of
      hyperactivity in children and adults with TS.

PMID- 15953500
TI  - Plasmodium chabaudi chabaudi (AS): differential cellular responses to infection
      in resistant and susceptible mice.
AB  - The infection with blood stages of Plasmodium chabaudi chabaudi (AS) was followed
      in BALB/c and DBA/2 mice. Both strains show a peak parasitemia by 7-9 days after
      infection, display splenic hypercellularity of T and B cells, thymic atrophy,
      nearly complete depletion of B cells in the bone marrow, and mount comparable
      polyclonal IgM and IgG responses in the serum. In contrast, these strains diverge
      in some aspects of the immune response and susceptibility to infection: while
      BALB/c survive, 70-80% of DBA/2 die within 2 weeks; BALB/c but not DBA/2 show
      marked increases in the levels of splenic gamma/delta and regulatory T cells,
      dendritic cells and macrophages and parasite-specific IgM and IgG levels;
      however, lower levels of TNF-alpha and IL-12 were observed. These results suggest
      the relevance of different cell populations that are known to
      participate/regulate specific antibody responses and cytokine production in the
      susceptibility to infection.

PMID- 15953501
TI  - Anterior vaginal wall surgery in elderly patients: outcomes and assessment.
AB  - OBJECTIVES: To evaluate the efficacy, safety, and impact on quality of life of
      anterior vaginal surgery in the elderly. Incontinence in the elderly is a
      devastating medical and social condition accounting for 50% of admissions to
      nursing homes; the incidence of anterior vaginal wall prolapse also increases in
      the elderly. Most patients are treated conservatively, because of a reluctance to
      offer surgical treatment to this age group owing to the perceived increased risk
      of complications and decreased rate of treatment success. METHODS: We
      prospectively evaluated all consecutive elderly patients who underwent anterior
      vaginal wall surgery between November 1999 and May 2003. The surgical outcomes
      were determined by the symptom, bother, and quality-of-life questionnaires
      answered by the patients. The physicians were unaware of the patients' responses.
      RESULTS: A total of 209 patients were available for analysis. The mean age was 70
      years (range 65 to 88) and the mean follow-up 15.3 months. All items in the
      symptom and bother questionnaires showed significant improvement. Significant
      improvement was also demonstrated in quality of life and pad use (P <0.005). No
      significant perioperative complications occurred. Only patients older than 71
      years of age did not experience an improvement in the symptom scores for urge
      incontinence. Nevertheless, as for all other patients, older patients experienced
      improvement in stress urinary incontinence (SUI) symptoms, the bother scores of
      SUI and urge incontinence, and quality of life. CONCLUSIONS: Surgical treatment
      of anterior vaginal wall prolapse and SUI in the elderly is effective and safe
      and significantly improves the quality of life of these patients.

PMID- 15953502
TI  - Targeting dyslipidemia--the key to CHD risk reduction in the diabetic population?

PMID- 15953503
TI  - Effective care of patients with type 2 diabetes and dyslipidemia: a nurse's
      perspective.
AB  - By 2030, it is predicted that type 2 diabetes will affect 4.4% of the world's
      population, an estimated 366 million individuals. Diabetic dyslipidemia is a
      modifiable risk factor for cardiovascular disease, which is a major cause of
      premature mortality in type 2 diabetes. The management of diabetic dyslipidemia
      requires a multidisciplinary approach and the role of the nurse within the
      healthcare team is pivotal. Their broad remit positions nurses not only at the
      forefront of care, where they are well placed to recognize the clinical signs of
      the condition, but also as patient advisor, counselor, educator, monitor and
      motivator during the continuum of care. Poor concordance is a common problem for
      patients receiving multiple medications. Educating the patient about the
      importance of lifestyle change, and ensuring that lifestyle and pharmacological
      interventions are sustained are important components of effective care. Choosing
      therapies that enable patients to reach their treatment goals with a simple
      dosage regimen may also help to maximize patient concordance. Nurses must remain
      up to date with treatment options and management guidelines in order that they
      can communicate relevant information to patients, empowering them to make
      informed decisions about their health. Specific, measurable, achievable, relevant
      and time-specific (SMART) goals should be set for each patient. This form of
      individualized care, in which the patient becomes fully engaged with their
      treatment plan and personal goals appear attainable, may help to reduce the
      projected burden of type 2 diabetes and its complications on healthcare services
      in the future.

PMID- 15953504
TI  - Cardiovascular risk: prevention and treatment of the metabolic syndrome.
AB  - The metabolic syndrome is a cluster of metabolic abnormalities, including
      impaired glucose metabolism, hypertension, dyslipidemia and abdominal obesity. It
      is a precursor to type 2 diabetes and a powerful independent risk factor for
      cardiovascular disease. Lifestyle changes, such as a diet high in saturated fats
      and a lack of physical exercise, have contributed to a worldwide increase in the
      prevalence of the metabolic syndrome and its associated complications.
      Identification and effective management of patients with the metabolic syndrome
      is important to reduce their risk of subsequent disease. Lifestyle modifications
      are an essential first step, and lipid-lowering therapy may also be required to
      achieve the lipid goals set out in current treatment guidelines. Statins are the
      most effective class of lipid-lowering drugs. Recent studies in patients with
      type 2 diabetes or the metabolic syndrome have shown that rosuvastatin was more
      effective than atorvastatin, simvastatin or pravastatin in reducing low-density
      lipoprotein cholesterol and enabling patients to reach lipid goals.

PMID- 15953505
TI  - The prevention of diabetic microvascular complications of diabetes: is there a
      role for lipid lowering?
AB  - The role of hyperglycemia in the development of microvascular complications of
      diabetes, such as nephropathy, retinopathy and neuropathy, has been well
      documented. Evidence is accumulating to support the concept that dyslipidemia can
      also contribute to the development of these complications. Lipid-lowering agents,
      such as statins, have been shown to prevent cardiovascular events in patients
      with diabetes. However, in addition to preventing macrovascular diseases, statins
      may also be able to retard the progression of microvascular complications of
      diabetes. Indeed, in addition to reducing lipid levels, these agents can improve
      endothelial function and reduce oxidative stress, which can improve microvascular
      function. These findings would provide further support for the use of lipid
      lowering agents in patients with diabetes.

PMID- 15953506
TI  - HDL-C and the diabetic patient: target for therapeutic intervention?
AB  - A low level of high-density lipoprotein cholesterol (HDL-C) is a key feature of
      the metabolic syndrome and type 2 diabetes. HDL particles exert an anti
      atherogenic effect, and low HDL-C levels are associated with increased
      cardiovascular disease risk. The profile of lipoprotein sub-classes may also be
      abnormal in patients with the metabolic syndrome or type 2 diabetes, with an
      excess of atherogenic small low-density lipoprotein (LDL) particles. Statins are
      first-line lipid-modifying drugs that, in addition to varying in their effects on
      LDL-C, differ in their effects on HDL-C. Rosuvastatin has been shown to be at
      least as effective at increasing HDL-C compared with atorvastatin, pravastatin or
      simvastatin. Selecting an agent that will increase HDL-C levels, as well as
      lowering LDL-C levels, may be particularly beneficial in the treatment of
      patients with the metabolic syndrome and type 2 diabetes.

PMID- 15953508
TI  - Cystic duct dilatation after cholecystectomy in fibropolycystic liver disease.

PMID- 15953509
TI  - Differential expression of two RXR/ultraspiracle isoforms during the life cycle
      of the hemimetabolous insect Blattella germanica (Dictyoptera, Blattellidae).
AB  - In insects, the molecular basis of ecdysteroid action has been analysed in great
      detail in flies and moths, but rarely in primitive orders. Using the primitive
      hemimetabolous insect Blattella germanica, the German cockroach, as a model, we
      isolated two cDNAs of RXR/USP, a component of the heterodimeric ecdysone
      receptor. These two cDNAs correspond to two isoforms, named BgRXR-S (short form)
      and BgRXR-L (long form). Both are identical except for a 23-amino acid
      deletion/insertion located in the loop between helices H1 and H3 of the ligand
      binding domain. Pattern expression studies show that the two isoforms are
      differentially expressed throughout the life cycle of B. germanica. During
      embryogenesis, BgRXR-L occurs in early embryos, whereas BgRXR-S is highly
      expressed in middle and late embryogenesis. In the penultimate and last larval
      instars, BgRXR-S mRNA is the predominant form in the fat body and in the
      prothoracic gland. In the adult female, BgRXR-S mRNA predominates in the fat
      body, whereas BgRXR-L mRNA predominates in the ovary. Experiments performed with
      fat body and embryo cells incubated in vitro showed that the expression of BgRXR
      S and BgRXR-L is not affected by 20-hydroxyecdysone or by juvenile hormone III.

PMID- 15953510
TI  - Localization of neurotensin immunoreactivity in neurons and organ of Corti of rat
      cochlea.
AB  - The distribution of neurotensin-containing cell bodies and fibers has been
      observed in the central and peripheral nervous system, including sensory ganglia,
      but no description has been found in the peripheral auditory system. Here, we
      investigated the presence of neurotensin immunoreactivity in the cochlea of the
      adult Wistar rat. Strong neurotensin immunoreactivity was detected in the
      cytoplasm of the inner hair cells (IHC) and Deiters' cells of the organ of Corti.
      Outer hair cells (OHC) show weak immunoreaction. Neurotensin immunoreactivity was
      also found in the neurons and fibers of the spiral ganglia. Quantitative
      microdensitometric image analysis of the neurotensin immunoreactivity showed a
      strong immunoreaction in the hair cells of organ of Corti and a moderate to
      strong labeling in the spiral ganglion neurons. A series of double immunolabeling
      experiments demonstrated a strong neurotensin immunoreactivity in the parvalbumin
      immunoreactive IHC and also in the calbindin immunoreactive Deiters' cells. Weak
      neurotensin immunoreactivity was seen in the calbindin positive OHC.
      Neurofilament and parvalbumin immunoreactive neurons and fibers in the spiral
      ganglia showed neurotensin immunoreactivity. Calbindin immunoreactivity was not
      detected in the spiral ganglion neurons, which are labeled by neurotensin
      immunoreactivity. The presence of neurotensin in the cochlea may be related to
      its modulation of neurotransmission in the peripheral auditory pathway.

PMID- 15953511
TI  - Perception of pitch by goldfish.
AB  - Classical conditioning and stimulus generalization methods have revealed much
      about the sense of hearing in non-human animals, and are now used here to
      investigate how goldfish perceive a variety of complex sounds, including multi
      harmonic complexes and rippled noise (RN). In several experiments, animals were
      conditioned to respond to one type of complex sound, and were then tested for
      generalization to other sounds differing along one or more acoustic dimensions
      from the conditioning sounds. Overall, generalization occurred only to the extent
      that the conditioning and test sounds were essentially similar in spectral range
      and, in most cases, waveform periodicity. For example, goldfish showed inverted V
      shaped generalization gradients to harmonic complexes varying in fundamental
      frequency after conditioning to complexes having a fundamental frequency of 100
      Hz. In several cases, similar gradients were observed whether the fundamental
      frequency component was present or absent in conditioning and testing complexes,
      indicating that goldfish, like other vertebrate listeners, do not "miss the
      fundamental" when it is missing. This generalization pattern tended to disappear
      when harmonic complexes were used that had random phase relations among the
      components, or slight mistuning of all components. In a few cases, patterns of
      generalization were determined by as yet unidentified acoustic features. Goldfish
      did not generalize to RN or harmonic complexes after conditioning to tones, and
      vice versa, in spite of the three signal types having fundamental frequency
      components and periodicity in common. Moreover, goldfish did not generalize
      robustly to infinitely iterated rippled noise after conditioning to harmonic
      complexes with a prominent periodic envelope, and vice versa, in spite of the two
      signal types having similar spectra and pitches as judged by human listeners.
      These and other results suggest that the pitch of harmonic complexes is prominent
      in goldfish generalization behavior and that this pitch-like dimension arises
      primarily from the signal's periodicity. The perceptions of single tones, RNs,
      and harmonic complexes having the same fundamental frequency are fundamentally
      different. It is concluded that the different perceptions of these signals arise
      in part from differences in periodic envelope prominence and spectral envelope,
      and possibly in the stochastic versus deterministic natures of their respective
      waveforms.

PMID- 15953512
TI  - Auditory nerve representation of naturally-produced vowels with variable
      acoustics.
AB  - This investigation compared the encoding of naturally-produced, whispered and
      normally-voiced vowels by auditory nerve fibers. Speech syllables containing the
      vowels /open o/ and /ae/ were produced by two female speakers and presented at
      three intensities to ketamine-anesthetized chinchillas. Six different
      representations of the spectral components in the vowels in the responses of the
      auditory nerve fibers were evaluated. For both normal and whispered vowels over a
      30 dB range, the formant peaks in the vowel were best displayed using rate-place
      representations. The spectral detail in the vowel was revealed by average
      localized synchronized rates (ALSR) and autocorrelations of individual
      peristimulus time histograms. The average localized interval rates (ALIR),
      autocorrelations of ensemble responses, and autocorrelations of individual spike
      trains demonstrated poor representations of vowel spectra, although the frequency
      components of normally-voiced vowels had better representations than those of
      whispered vowels. These analyses suggest that rate-based and synchronization
      based measures yields two very different pieces of information, but only a
      normalized rate-based measure consistently identified the formants of both the
      whispered and normally-voiced vowels.

PMID- 15953513
TI  - ATP-gamma-S shifts the operating point of outer hair cell transduction towards
      scala tympani.
AB  - ATP receptor agonists and antagonists alter cochlear mechanics as measured by
      changes in distortion product otoacoustic emissions (DPOAE). Some of the effects
      on DPOAEs are consistent with the hypothesis that ATP affects mechano-electrical
      transduction and the operating point of the outer hair cells (OHCs). This
      hypothesis was tested by monitoring the effect of ATP-gamma-S on the operating
      point of the OHCs. Guinea pigs anesthetized with urethane and with sectioned
      middle ear muscles were used. The cochlear microphonic (CM) was recorded
      differentially (scala vestibuli referenced to scala tympani) across the basal
      turn before and after perfusion (20 min) of the perilymph compartment with
      artificial perilymph (AP) and ATP-gamma-S dissolved in AP. The operating point
      was derived from the cochlear microphonics (CM) recorded in response low
      frequency (200 Hz) tones at high level (106, 112 and 118 dB SPL). The analysis
      procedure used a Boltzmann function to simulate the CM waveform and the Boltzmann
      parameters were adjusted to best-fit the calculated waveform to the CM. Compared
      to the initial perfusion with AP, ATP-gamma-S (333 microM) enhanced peak clipping
      of the positive peak of the CM (that occurs during organ of Corti displacements
      towards scala tympani), which was in keeping with ATP-induced displacement of the
      transducer towards scala tympani. CM waveform analysis quantified the degree of
      displacement and showed that the changes were consistent with the stimulus being
      centered on a different region of the transducer curve. The change of operating
      point meant that the stimulus was applied to a region of the transducer curve
      where there was greater saturation of the output on excursions towards scala
      tympani and less saturation towards scala vestibuli. A significant degree of
      recovery of the operating point was observed after washing with AP. Dose response
      curves generated by perfusing ATP-gamma-S (333 microM) in a cumulative manner
      yielded an EC(50) of 19.8 microM. The ATP antagonist PPADS (0.1 mM) failed to
      block the effect of ATP-gamma-S on operating point, suggesting the response was
      due to activation of metabotropic and not ionotropic ATP receptors. Multiple
      perfusions of AP had no significant effect (118 and 112 dB) or moved the
      operating point slightly (106 dB) in the direction opposite of ATP-gamma-S.
      Results are consistent with an ATP-gamma-S induced transducer change comparable
      to a static movement of the organ of Corti or reticular lamina towards scala
      tympani.

PMID- 15953514
TI  - Effect of aspirin on phase gradient of 2F1-F2 distortion product otoacoustic
      emissions.
AB  - It is well known that aspirin consumption temporarily reduces overall otoacoustic
      emission (OAE) amplitude in humans. However, little is known about changes in the
      separate components of distortion product otoacoustic emissions (DPOAE), which
      may be distinguished by examining phase gradients. The effects of aspirin on the
      phase gradient of the DPOAE 2F1-F2 obtained with fixed frequency ratio sweeps
      were studied longitudinally in a group of twelve subjects in whom a temporary
      hearing loss was induced by aspirin consumption. DPOAE were recorded daily for
      two days pre-aspirin consumption, during the three days of aspirin consumption
      and two days afterwards. DP-grams were recorded over a restricted frequency range
      centered on 2,3,4 and 6 kHz with the following stimulus levels: L1/L2 of 60/50
      80/70 in 10-dB steps. The effects of aspirin on the phase gradients varied
      between the subjects and across frequency: the general trend was that the phase
      gradient became steeper across successive sessions for the higher frequencies,
      while no significant effect was found at the lower frequencies. These results
      suggest that aspirin may have more persistent effects on cochlear function than
      are disclosed by measurements of hearing threshold level or DPOAE amplitude.
      Particularly, DPOAE phase gradient appears to be increased by aspirin consumption
      and has not recovered two days after cessation of aspirin intake, despite almost
      complete recovery of DPOAE amplitude and hearing threshold levels. These findings
      may suggest differential effects on the distortion and reflection mechanisms
      considered to underlie DPOAE generation.

PMID- 15953515
TI  - Influence of cochlear traveling wave and neural adaptation on auditory brainstem
      responses.
AB  - The present study investigates the relationship between evoked responses to
      transient broadband chirps and responses to the same chirps when embedded in
      longer-duration stimuli. It examines to what extent the responses to the
      composite stimuli can be explained by a linear superposition of the responses to
      the single components, as a function of stimulus level. In the first experiment,
      a single rising chirp was temporally and spectrally embedded in two steady-state
      tones. In the second experiment, the stimulus consisted of a continuous
      alternating train of chirps: each rising chirp was followed by the temporally
      reversed (falling) chirp. In both experiments, the transitions between stimulus
      components were continuous. For stimulation levels up to approximately 70 dB SPL,
      the responses to the embedded chirp corresponded to the responses to the single
      chirp. At high stimulus levels (80-100 dB SPL), disparities occurred between the
      responses, reflecting a nonlinearity in the processing when neural activity is
      integrated across frequency. In the third experiment, the effect of within-train
      rate on wave-V response was investigated. The response to the chirp presented at
      a within-train rate of 95 Hz exhibited the same amplitude as that to the chirp
      presented in the traditional single-stimulus paradigm at a rate of 13 Hz. For a
      corresponding experiment with bandlimited chirps of 4 ms duration, where the
      within-train rate was 250 Hz, a clear reduction of the response amplitude was
      observed. This nonlinearity in terms of temporal processing most likely reflects
      effects of short-term adaptation. Overall, the results of the present study
      further demonstrate the importance of cochlear processing for the formation of
      brainstem potentials. The data may provide constraints on future models of
      peripheral processing in the human auditory system. The findings might also be
      useful for the development of effective stimulation paradigms in clinical
      applications.

PMID- 15953516
TI  - Reduced expression of sialoglycoconjugates in the outer hair cell glycocalyx
      after systemic aminoglycoside administration.
AB  - In this study we investigated the effect of systemic aminoglycoside
      administration on the expression of sialoglycoconjugates in the outer hair cell
      (OHC) glycocalyx of the adult guinea pig. Sialoglycoconjugates were visualized by
      means of ultrastructural lectin cytochemistry, using Limax flavus agglutinin
      (LFA) and wheat germ agglutinin (WGA) as probes. Labelling densities were
      determined for the apical membranes (including the stereocilia and stereociliary
      cross-links) and basolateral membranes of OHCs in the respective (basal, middle
      and apical) cochlear turns from animals that had been treated with gentamicin or
      neomycin for 5 or 15 consecutive days. Our results indicate that: (1)
      sialoglycoconjugate expression in the OHC glycocalyx demonstrates an
      intracochlear gradient decreasing towards the apical turn; (2) OHCs demonstrate a
      polarity in sialoglycoconjugate expression, in that the basolateral membranes
      contain more sialoglycoconjugates per surface area than the apical membranes; (3)
      aminoglycoside administration results in reduced expression of
      sialoglycoconjugates in the OHC glycocalyx; in this respect, basal-turn OHCs are
      more susceptible than those in the middle and apical turns; (4) reduction in
      sialoglycoconjugate expression after aminoglycoside administration is more
      prominent in the basolateral membranes; and (5) the difference in ototoxic
      potencies between gentamicin and neomycin is not reflected at the level of
      sialoglycoconjugate expression. The present data support our earlier hypothesis
      that aminoglycosides, already at an early phase of intoxication, interfere with
      the function of the endoplasmic reticulum and/or the Golgi apparatus, implying
      that these organelles play a crucial role in the initial phase of aminoglycoside
      induced OHC degeneration.

PMID- 15953517
TI  - Histopathology of human cochlear implants: correlation of psychophysical and
      anatomical measures.
AB  - The cadavaric temporal bones of five subjects who underwent cochlear implantation
      during life (2 Nucleus and 3 Ineraid) were analyzed using two-dimensional (2D)
      reconstruction of serial sections to determine the number of surviving spiral
      ganglion cells (SGCs) in the region of each electrode of the implanted arrays.
      The last psychophysical threshold and maximum-comfortable sensation level
      measured for each electrode were compared to their respective SGC count to
      determine the across-electrode psychophysical variance accounted for by the SGC
      counts. Significant correlations between psychophysical measures and SGC counts
      were found in only two of the five subjects: one Nucleus implantee (e.g., r=
      0.71; p<0.001 for threshold vs. count) and one Ineraid implantee (e.g., r=-0.86;
      p<0.05 for threshold vs. count). A three-dimensional (3D) model of the implanted
      cochlea was formulated using the temporal-bone anatomy of the Nucleus subject for
      whom the 2D analysis did not result in significant correlations between counts
      and psychophysical measures. Predictions of the threshold vs. electrode profile
      were closer to the measured profile for the 3D model than for the 2D analysis.
      These results lead us to hypothesize that 3D techniques will be required to asses
      the impact of peripheral anatomy on the benefit patients derive from cochlear
      implantation.

PMID- 15953518
TI  - Use of time differences in normal hearing--cortical processing of promontorial
      stimuli.
AB  - To test the hypothesis that ability to discriminate small duration differences is
      positively correlated with activity in the right temporal lobe, we used positron
      emission tomography in six normally hearing subjects, stimulated via the
      promontory in a procedure that mimics the auditory nerve stimulation with a
      cochlear implant. Stimulus consisted of electrical bursts, and tasks included gap
      detection and temporal difference limen (TDL). TDL is a measure of discriminatory
      processing of sound duration in cochlear implant candidates, demonstrated to
      predict outcome. Good speech perception after cochlear implantation is associated
      with activity in right temporal areas. Although perceived variably by the
      subjects, the stimulus itself activated bilateral secondary somatosensory cortex,
      suggesting differential stimulation of multiple sensory modalities. Only TDL
      raised blood flow in both posterior middle temporal gyri (MTG) and the right
      prefrontal cortex. As the right posterior MTG is known to be active during
      duration discrimination of different modalities and in the perception of words
      containing manipulated phonemes, we conclude that recruitment of this part of the
      right hemisphere is important to the comprehension of speech containing mostly
      temporal cues. The study shows that stimulus-induced activation reflects the goal
      of the task rather than the nature of the stimulus.

PMID- 15953519
TI  - Correlation of increased activities of Na+, K+-ATPase and Ca2+-ATPase with the
      reversal of cisplatin ototoxicity induced by D-methionine in guinea pigs.
AB  - Na(+), K(+)-ATPase and Ca(2+)-ATPase in the cochlear lateral wall play an
      important role in maintaining ionic homeostasis and physiologic function of the
      cochlea. The present study was designed to test whether the changes of Na(+),
      K(+)-ATPase and Ca(2+)-ATPase activities of the cochlear lateral wall and the
      brainstem of guinea pigs after receiving cisplatin for seven consecutive days
      were correlated with the altered auditory brainstem responses (ABR). Furthermore,
      whether a chemoprotective agent, D-methionine reversed the increased ABR
      threshold induced by cisplatin accompanied with the increased ATPase activities
      was also evaluated. The results obtained showed that cisplatin exposure caused
      not only a significant increase of threshold but also altered various absolute
      wave and interwave latencies of ABR. In addition, cisplatin significantly
      decreased the Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the cochlear
      lateral wall with a good dose-response relationship. Regression analysis
      indicated that an increase of ABR threshold was well correlated with a decrease
      of both Na(+), K(+)-ATPase and Ca(2+)-ATPase activities in the cochlear lateral
      wall. A chemoprotectant, D-methionine indeed reversed both abnormalities of ABR
      and ATPase activities in a well correlation function. The selectivity of these
      observed changes induced by cisplatin and D-methionine was revealed by the
      findings that cisplatin-treated guinea pigs had normal III-V interwave latency of
      ABR and no reduction of Na(+), K(+)-ATPase and Ca(2+)-ATPase specific activities
      in the brainstem, which is in accordance with the nonpenetrable cisplatin across
      the blood brain barrier. Taken all together, the present findings suggest that
      biochemical damage and ionic disturbance may contribute to cisplatin-induced
      ototoxicity to some extent, which can be reversed by d-methionine.

PMID- 15953520
TI  - Asphyxia and depolarization increase adenosine levels in perilymph.
AB  - Extracellular adenosine has been suggested as a modulator of cochlear function.
      To date the release of adenosine into the extracellular spaces of the cochlea has
      not been demonstrated. Therefore, experiments were designed to examine whether
      adenosine release into perilymph could be detected in response to depolarization
      by high potassium concentrations or in response to asphyxia. For this purpose,
      the perilymph compartment of guinea pigs was perfused with an artificial
      perilymph and the effluent assayed for ATP, ADP, AMP and adenosine. Results
      indicate that potassium induced a slight, significant increase and asphyxia
      induced a very large, significant increase in adenosine levels in perilymph
      effluent. No changes in the levels of the other compounds were measured. It is
      concluded that depolarization and asphyxia can induce the release of adenosine
      into perilymph.

PMID- 15953521
TI  - Cochlear implantation in rats: a new surgical approach.
AB  - The laboratory rat has been used extensively in auditory research but has had
      limited use in cochlear implant related research due mainly to the surgically
      restricted access to the scala tympani. We have developed a new surgical method
      for cochlear implantation in rats. The key to this protocol was cauterizing the
      stapedial artery (SA) and making a small cochleostomy near the round window in
      order to enlarge the surgical access to the scala tympani. Five normal hearing
      Hooded Wistar rats were used to investigate the effect of cauterizing the SA on
      hearing and auditory nerve survival. Results showed that cauterizing the SA was
      surgically feasible, afforded excellent exposure of the round window niche for
      cochleostomy, and did not adversely affect acoustic thresholds measured
      electrophysiologically. Moreover, there was no difference in spiral ganglion cell
      densities for any cochlear turn when compared with the contralateral control
      ears. Three deafened rats were subsequently implanted with a scala tympani
      electrode array using this new surgical approach. Electrically evoked auditory
      brainstem responses using bipolar stimulation, and subsequent cochlear
      histopathology demonstrated that cochlear implantation using a custom-made rat
      electrode array was safe and effective. The surgical approach presented in this
      paper presents a safe and effective procedure for acute or chronic cochlear
      implantation in the rat model.

PMID- 15953522
TI  - The association between short stature and sensorineural hearing loss.
AB  - In order to test the Thrifty Phenotype Hypothesis on hearing, data from two cross
      sectional studies on hearing were re-evaluated. The data sets comprised 500 18
      year-old conscripts, and 483 noise-exposed male employees. Sensorineural hearing
      loss (SNHL) was over-represented among conscripts with a short stature (odds
      ratio=2.2) or hearing loss in the family (odds ration=4.2), but not among noise
      exposed conscripts (odds ratio=0.9-1.3). Among noise-exposed short employees,
      hypertension and age exhibited a negative impact on high frequency hearing
      thresholds, while among tall employees hypertension had no effect on hearing and
      the influence of age was less pronounced (p<0.01 for body height; p<0.02 for age,
      hypertension and the interaction between body height and hypertension; p<0.05 for
      the interaction between body height and age). This suggests that mechanisms
      linked to fetal programming and growth retardation and/or insulin-like growth
      factor 1 levels during fetal life, such as a delayed cell cycle during the time
      window when the cochlea develops, may cause SNHL in adulthood.

PMID- 15953523
TI  - The auditory acclimatization effect in sensorineural hearing-impaired listeners:
      evidence for functional plasticity.
AB  - The present study provides new data on perceptual and physiological modifications
      associated with hearing aid (HA) fitting. Eight sensorineural hearing-impaired
      (SNHI) listeners participated. They had symmetrical hearing loss and were being
      fitted with binaural HAs for the first time. Perceptual performances were
      measured four times during auditory rehabilitation, using an intensity
      discrimination task and a loudness-scaling task. Pure tones of two different
      frequencies were used, one well amplified by HAs and the other weakly amplified.
      Two intensity levels were also tested, one rated 'soft' by SNHI listeners and the
      other 'loud'. Auditory brainstem responses (ABRs) to click stimulation were
      recorded. All measures were performed without HA. Results were consistent with
      the auditory acclimatization effect: most modifications induced by HA fitting
      were found at loud intensity levels and at high frequency, i.e., for acoustic
      information that was newly available to the listener. While both ears had similar
      hearing loss and aided gains, some differences between ears appeared in both
      perceptual tasks and in ABRs. In the right ear, a shortening of wave V latency
      paralleled perceptual modifications. The present results suggest that HA-fitting
      induces functional plasticity at the peripheral level of the auditory system.

PMID- 15953524
TI  - Unraveling the electrically evoked compound action potential.
AB  - With the advent of eCAP recording tools such as NRT and NRI for cochlear
      implants, neural monitoring has become widely used to ascertain the integrity of
      the neural/electrode interface as well as for assisting in the setting of program
      levels. The basic concepts of eCAP recordings are deduced from the acoustical
      equivalent of the electrocochleogram. There are, however, indications that under
      electrical stimulation some of these do not hold, like the unitary response
      concept (i.e., the principle that every fiber produces the same contribution to
      the eCAP). Computer modeling has proven to be a valuable tool for gaining insight
      into the functioning of electrical stimulation. In this study the extension of a
      three-dimensional human cochlea, incorporating back-measuring capabilities, is
      described. Using this new model, the contribution of single fiber action
      potentials (SFAPs) to the measured eCAP is investigated. The model predicts that
      contrary to common belief--the compound action potential as measured by the
      cochlear implant system does not necessarily reflect the propagated action
      potential along the auditory nerve.

PMID- 15953525
TI  - Neural correlates of the precedence effect in auditory evoked potentials.
AB  - The precedence effect in subjective localization tasks reflects the dominance of
      directional information of a direct sound (lead) over the information provided by
      one or several reflections (lags) for short delays. By collecting data of both
      psychoacoustical measurements and auditory evoked potentials the current study
      aims at neurophysiological correlates for the precedence effect in humans. In
      order to investigate whether the stimulus features or the perception of the
      stimulus is reflected on the ascending stages of the human auditory pathway,
      auditory brainstem responses (ABRs) as well as cortical auditory evoked
      potentials (CAEPs) using double click-pairs were recorded. Potentials were
      related to the results of the psychoacoustical data. ABRs to double click-pairs
      with lead-lag delays from 0 to 20 ms and interaural time differences (ITDs) in
      the lag click of 0 and 300 micros show an emerging second wave V for lead-lag
      delays larger than 2 ms. The amplitudes of the first and second wave V are the
      same for a lead-lag delay of about 5 ms. For the lag-ITD stimuli the latency of
      the second wave V was prolonged by approximately ITD/2 compared to the stimuli
      without lag-ITD. As the amplitudes of the second wave V were not decreased for a
      lead-lag delay around 5 ms as could be expected from psychoacoustical
      measurements of the precedence effect, ABRs reflect stimulus features rather than
      the perceptive qualities of the stimulus. The mismatch negativity (MMN) component
      of the CAEP for double click-pairs was determined using a diotic standard and a
      deviant with an ITD of 800 micros in the lag click. The comparison between the
      MMN components and the psychoacoustical data shows that the MMN is related to the
      perception of the stimulus, i.e., to the precedence effect. Generally, the
      findings of the present study suggest that the precedence effect is not a result
      of a poor sensitivity of the peripheral bottom-up processing. Rather, the
      precedence effect seems to be reflected by the MMN, i.e., cognitive processes on
      higher stages of the auditory pathway.

PMID- 15953526
TI  - Cochlear compression in listeners with moderate sensorineural hearing loss.
AB  - Psychophysical estimates of basilar membrane (BM) responses suggest that normal
      hearing (NH) listeners exhibit constant compression for tones at the
      characteristic frequency (CF) across the CF range from 250 to 8000 Hz. The
      frequency region over which compression occurs is broadest for low CFs. This
      study investigates the extent that these results differ for three hearing
      impaired (HI) listeners with sensorineural hearing loss. Temporal masking curves
      (TMCs) were measured over a wide range of probe (500-8000 Hz) and masker
      frequencies (0.5-1.2 times the probe frequency). From these, estimated BM
      response functions were derived and compared with corresponding functions for NH
      listeners. Compressive responses for tones both at and below CF occur for the
      three HI ears across the CF range tested. The maximum amount of compression was
      uncorrelated with absolute threshold. It was close to normal for two of the three
      HI ears, but was either slightly (at CFs < or =1000 Hz) or considerably (at CFs >
      or =4000 Hz) reduced for the third ear. Results are interpreted in terms of the
      relative damage to inner and outer hair cells affecting each of the HI ears.
      Alternative interpretations for the results are also discussed, some of which
      cast doubts on the assumptions of the TMC-based method and other behavioral
      methods for estimating human BM compression.

PMID- 15953527
TI  - Auditory cortical activation and speech perception in cochlear implant users:
      effects of implant experience and duration of deafness.
AB  - This study aimed to investigate the relationship between outcome following
      cochlear implantation and auditory cortical activation. It also studied the
      effects of length of implant use and duration of deafness on the auditory
      cortical activations. Cortical activity resulting from auditory stimulation was
      measured using [(18)F]FDG positron emission tomography. In a group of 18
      experienced adult cochlear implant users, we found a positive correlation between
      speech perception and activations in both the primary and association auditory
      cortices. This correlation was present in a subgroup of experienced implant users
      but absent in a group of new implant users with similar speech perception
      abilities. There was a significant negative correlation between duration of
      deafness and auditory cortical activation. This study gives insights into the
      relationship between implant speech perception and auditory cortical activation
      and the influence of duration of preceding deafness and implant experience.

PMID- 15953528
TI  - Predicting the effect of post-implant cochlear fibrosis on residual hearing.
AB  - Intracochlear scarring is a well-described sequela of cochlear implantation. We
      developed a mathematical model of passive cochlear mechanics to predict the
      impact that this might have upon residual acoustical hearing after implantation.
      The cochlea was modeled using lumped impedance terms for scala vestibuli (SV),
      scala tympani (ST), and the cochlear partition (CP). The damping of ST and CP was
      increased in the basal one half of the cochlea to simulate the effect of scar
      tissue. We found that increasing the damping of the ST predominantly reduced
      basilar membrane vibrations in the apex of the cochlea while increasing the
      damping of the CP predominantly reduced basilar membrane vibrations in the base
      of the cochlea. As long as intracochlear scarring continues to occur with
      cochlear implantation, there will be limitations on hearing preservation. Newer
      surgical techniques and electrode technologies that do not result in as much scar
      tissue formation will permit improved hearing preservation.

PMID- 15953529
TI  - Disruption and restoration of cell-cell junctions in mouse vestibular epithelia
      following aminoglycoside treatment.
AB  - The intracellular junction complexes, which consist of tight junctions (TJ),
      adherens junctions (AJ), and desmosomes, mediate cell-cell adhesion in epithelial
      cells. E-cadherin, which is a major component of AJ, plays a role not only in the
      maintenance of cell-cell junctions, but also in repressing cell proliferation. In
      this study, we examined changes of E-cadherin expression in mouse vestibular
      epithelia following local application of neomycin using immunohistochemistry and
      western blotting, and morphology of cell-cell junctions by transmission electron
      microscopy (TEM). Immunohistochemistry and western blotting revealed down
      expression of E-cadherin and its consecutive recovery. TEM demonstrated temporal
      disruption of cell-cell junctions. Morphology of cell-cell junctions was more
      rapidly restored than recovery of E-cadherin expression. Transient disruption of
      cell-cell junctions and down-expression of E-cadherin is a rational response for
      the deletion of dying hair cells, and may be associated with a limited capacity
      for cell proliferations in mammalian vestibular epithelia following their rapid
      restoration.

PMID- 15953530
TI  - Effect of inter-phase gap on the sensitivity of cochlear implant users to
      electrical stimulation.
AB  - Human behavioral thresholds for trains of biphasic pulses applied to a single
      channel of Nucleus CI24 and LAURA cochlear implants were measured as a function
      of inter-phase gap (IPG). Experiment 1 used bipolar stimulation, a 100-pps pulse
      rate, and a 400-ms stimulus duration. In one condition, the two phases of each
      pulse had opposite polarity. Thresholds continued to drop by 9-10 dB as IPG was
      increased from near zero to the longest value tested (2900 micros for CI24, 4900
      micros for LAURA). This time course is much longer than reported for single-cell
      recordings from animals. In a second condition, the two phases of each pulse had
      the same polarity, which alternated from pulse to pulse. Thresholds were
      independent of IPG, and similar to those in condition 1 at IPG=4900 micros.
      Experiment 2 used monopolar stimulation. One condition was similar to condition 1
      of experiment 1, and thresholds also dropped up to the longest IPG studied (2900
      micros). This also happened when the pulse rate was reduced to 20 pps, and when
      only a single pulse was presented on each trial. Keeping IPG constant at 8 micros
      and adding an extra biphasic pulse x ms into each period produced thresholds that
      were roughly independent of x, indicating that the effect of IPG in the other
      conditions was not due to a release from refractoriness at sites central to the
      auditory nerve. Experiment 3 measured thresholds at three IPGs, which were less
      than, equal to, and more than one half of the interval between successive pulses.
      Thresholds were lowest at the intermediate IPG. The results of all experiments
      could be fit by a linear model consisting of a lowpass filter based on the
      function relating threshold to the frequency of sinusoidal electrical
      stimulation. The data and model have implications for reducing the power
      consumption of cochlear implants.

PMID- 15953531
TI  - Pathologic changes of presbycusis begin in secondary processes and spread to
      primary processes of strial marginal cells.
AB  - Strial atrophy underlying age-related hearing loss was investigated by
      ultrastructural comparisons in young and senescent gerbils. In young animals
      strial marginal cells (MCs) projected primary processes which gave rise to and
      were connected by numerous ultrathin secondary processes. In 30-36-month-old
      gerbils, the MC secondary processes degenerated into lamellar or amorphous
      profiles as the first manifestation of strial atrophy. Some short primary
      processes shorn of projecting and connecting secondaries coalesced to form
      mitochondria-filled lobules. Strial involution appeared to progress with
      transformation of the degenerating processes and lobules into permanent residues
      of laminated amorphous substance. A second apparently unique form of degeneration
      was observed in which areas filled with homogeneous granular material replaced
      the processes that comprise the basal half of the normal MC. An abrupt line of
      transition separated this structureless degradation product below from the viable
      upper half of the MC. The terminally involuted stria consisted of MC bodies
      lining scala media, along with vestigial remnants of MC processes, nearby normal
      appearing intermediate cells (ICs) and unaltered basal cells. The only age
      related change in ICs involved incorporation of melanosomes into very large,
      matrix-filled lysosomes. A profile of one MC in apparent necrosis provided
      evidence for an infrequent occurrence of MC death. These data support a
      progression of pathologic changes beginning with the demise of MC secondary
      processes and ending with ablation of secondary and primary processes. The
      initial injury apparently occurs as a result of oxidative self-damage to
      mitochondria in the MCs primary processes, leading to insufficient ATP for the
      Na,K-ATPase of the secondary processes. The reduced ATP level may cause cytotoxic
      alteration of the cytosolic Na(+)/K(+) ratio first in MC secondary processes and
      later in the primaries, with consequent degeneration of these structures.

PMID- 15953532
TI  - The cochlear targets of cisplatin: an electrophysiological and morphological time
      sequence study.
AB  - Cisplatin ototoxicity has at least three major targets in the cochlea: the stria
      vascularis, the organ of Corti, and the spiral ganglion. This study aims to
      differentiate between these three targets. In particular, we address the question
      of whether the effects at the level of the organ of Corti and spiral ganglion are
      mutually dependent or whether they develop in parallel. This question was
      approached by studying the ototoxic effects while they develop
      electrophysiologically and comparing these to earlier presented histological data
      [Van Ruijven et al., 2004. Hear. Res. 197, 44-54]. Guinea pigs were treated with
      intraperitoneal injections of cisplatin at a dose of 2 mg/kg/day for either 4, 6,
      or 8 consecutive days. This time sequence has not revealed any evidence of one
      ototoxic process triggering another. Therefore, we have to stay with the
      conclusion of Van Ruijven et al. (2004) that both processes run in parallel.

PMID- 15953533
TI  - Time-frequency analysis of transiently evoked otoacoustic emissions of subjects
      exposed to noise.
AB  - Transiently evoked otoacoustic emissions (TEOAE) were measured from 124 ears from
      two subject groups: healthy subjects (62 ears), and workers (62 ears) exposed to
      noise of jet engines. The recordings were analyzed using the method of adaptive
      approximations based on a matching pursuit (MP) algorithm. The method allows for
      description of the signal components in terms of their amplitude, frequency,
      latency, and time-span (or duration). The purpose of this work was to determine
      the repeatability and usefulness of these parameters in studies of hearing
      impairment of populations exposed to potentially harmful noise. Good distinction
      between the two datasets was achieved in all investigated frequency bands when
      amplitude was used as a discrimination parameter. Also latency was affected in
      frequency bands starting at 2000 Hz, while the time-span parameter associated
      with the duration of the waveform was less influenced by noise.

PMID- 15953534
TI  - Auditory evoked magnetic fields in relation to iterated rippled noise.
AB  - Auditory evoked magnetic fields in relation to iterated rippled noise (IRN) were
      examined by magnetoencephalography (MEG). IRN was used as the sound stimulus to
      control the peak amplitude of the autocorrelation function of the sound. The IRN
      was produced by a delay-and-add algorithm applied to bandpass noise that was
      filtered using fourth-order Butterworth filters between 400-2200 Hz. All sound
      signals had the same sound pressure level. The stimulus duration was 0.5 s, with
      rise and fall ramps of 10 ms. Ten normal-hearing subjects took part in the study.
      Auditory evoked fields were recorded using a 122 channel whole-head magnetometer
      in a magnetically shielded room. The results showed that the peak amplitude of
      N1m, which was found above the left and right temporal lobes around 100 ms after
      the stimulus onset, increased with increase in the number of iterations of the
      IRN. The latency and estimated equivalent current dipole (ECD) locations of N1m
      did not show any systematic variation as a function of the number of iterations.

PMID- 15953535
TI  - Construction of an expression system for the motor protein prestin in Chinese
      hamster ovary cells.
AB  - The electromotility of outer hair cells (OHCs) is believed to be a major factor
      in cochlear amplification that enables the high sensitivity of hearing in
      mammals. This motility is thought to be based on voltage-dependent conformational
      changes of a motor protein embedded in the lateral wall of the OHC. In 2000, this
      motor protein was identified and termed prestin. To obtain knowledge on the
      function of prestin, research at the molecular level is necessary. For this
      purpose, a method of obtaining a large amount of prestin is required. In this
      study, an attempt was therefore made to construct an expression system for
      prestin. Prestin cDNA was introduced into Escherichia coli (E. coli), insect
      cells and Chinese hamster ovary (CHO) cells, and the expression of prestin was
      examined by Western blotting. As CHO cells expressed prestin well, we generated
      prestin-expressing cell lines using CHO cells by limiting dilution cloning. The
      stable expression and the activity of prestin in generated cell lines were then
      confirmed. Finally, to obtain prestin from these cell lines efficiently, culture
      conditions of the cells were examined, and it was clarified that cells should be
      cultured in serum-free medium and harvested around 48 h after passage.

PMID- 15953536
TI  - Salicylate blocks L-type calcium channels in rat inferior colliculus neurons.
AB  - To investigate the effects of the tinnitus inducer sodium salicylate on L-type
      voltage-gated calcium channels, we studied freshly dissociated inferior
      colliculus neurons of rats by the whole-cell voltage clamp method. Salicylate's
      blocking of L-type calcium channels was concentration dependent, and the IC(50)
      value of salicylate was estimated to be 1.99 mM. An amount of 1 mM salicylate
      significantly shifted the steady-state inactivation curve of L-type calcium
      channels about 9 mV in the hyperpolarizing direction and significantly delayed
      calcium channel recovery. Our results suggest that salicylate's blocking of L
      type calcium channels may contribute to salicylate-induced tinnitus by decreasing
      GABA release in the inferior colliculus.

PMID- 15953537
TI  - Click-evoked myogenic potentials recorded on alert guinea pigs.
AB  - The aim of this study was to establish an animal model of acoustically evoked
      vestibulo-collic reflex using guinea pigs. A special clamp was applied to
      restrain the head and body of the guinea pigs, but leaving its four legs free.
      Each animal underwent vestibular evoked myogenic potential (VEMP) and caloric
      tests using clip electrode method without general anesthesia or decerebrate
      surgery. The response rates for the myogenic potentials on the neck of guinea
      pigs using 100, 90, 80 and 70 dB monaural acoustic stimulation with unilateral
      recording were 100%, 62%, 50% and 0%, respectively. The mean latencies of the
      positive and negative peaks for the myogenic potentials were 7.24+/-0.49 and
      9.15+/-0.47 ms, 7.09+/-0.43 and 9.28+/-0.42 ms, as well as 7.03+/-0.59 and 9.14+/
      0.56 ms, when elicited by 100, 90 and 80 dB acoustic stimulation, respectively.
      The median (minimum-maximum) peak-to-peak amplitudes were 11.93 (6.14-16.86),
      10.99 (5.28-19.40), and 11.17 (5.02-20.72) microV, when elicited by 100, 90 and
      80 dB acoustic stimulation, respectively. We found no significant relationship
      between the stimulus intensity and the mean latencies or peak-to-peak amplitude
      of the myogenic potentials in guinea pigs. For those treated with gentamicin
      unilaterally, all guinea pigs showed absent caloric responses on the lesion side,
      and absent myogenic potentials on the neck when using ipsi-lesional acoustic
      stimulation, while the hearing was preserved. Hence, the use of gentamicin
      treated animals, along with normal controls and auditory brainstem responses,
      results in convincing results that the recorded myogenic potentials are in fact
      of vestibular origin.

PMID- 15953538
TI  - Overlap of the gene encoding the novel poly(ADP-ribose) polymerase Parp10 with
      the plectin 1 gene and common use of exon sequences.
AB  - We have recently identified PARP10 as a novel functional poly(ADP-ribose)
      polymerase. The gene encoding PARP10 is conserved in vertebrates but no orthologs
      were found in lower organisms. In addition to the poly(ADP-ribose) polymerase
      domain, PARP10 possesses several additional sequence motifs, including an RNA
      recognition motif and two ubiquitin interaction motifs. We characterized the
      murine genomic locus of the Parp10 gene. We noticed that 3' Parp10 sequences
      overlapped with the plectin 1 gene in a head-to-tail arrangement. Detailed
      analyses revealed that the two most 3' Parp10 exons (exons 10 and 11) are also
      used for plectin 1. While these two exons code for part of the poly(ADP-ribose)
      polymerase domain in Parp10, they are noncoding for plectin 1 due to the lack of
      appropriate start codons. Furthermore our findings suggest that at least one of
      the plectin 1 promoters is located within intron 9 of the Parp10 gene.

PMID- 15953539
TI  - Analysis of recombination and gene distribution in the 2L1.0 region of wheat
      (Triticum aestivum L.) and barley (Hordeum vulgare L.).
AB  - Both wheat and barley belong to tribe Triticeae and are closely related. High
      density detailed comparison of physical and genetic linkage maps revealed that
      wheat genes are present in physically small gene-rich regions (GRRs). One of the
      largest GRRs is located around fraction length 1.0 of the long arm of wheat
      homoeologous group 2 chromosomes termed the "2L1.0 region." The main objective of
      this study was to analyze the structural and functional organization of the 2L1.0
      region in barley in comparison to wheat. Using the 29 physically mapped RFLP
      markers for the region, wheat and barley consensus genetic linkage maps of the
      2L1.0 region were generated by combining information from 18 wheat and 7 barley
      genetic linkage maps. Comparative analysis using these consensus maps and other
      available wheat and barley mapping resources identified 227 DNA markers and ESTs
      for the region. The region accounted for 58% of the genes and 68% of the arm's
      recombination in wheat. However, the corresponding region in barley accounted for
      about 42% of the genes and 81% of the recombination. The kb/cM ratio for the
      region was 122 in barley compared to 244 in wheat. Distribution of genes and
      recombination varied between the two species even though the gene order and
      density were similar.

PMID- 15953540
TI  - Identifying new candidate genes for hereditary facial paresis on chromosome 3q21
      q22 by RNA in situ hybridization in mouse.
AB  - Hereditary congenital facial paresis (HCFP) belongs to the family of congenital
      cranial dysinnervation disorders and is characterized by an isolated dysfunction
      of the facial nerve (nVII). While genetic defects have been identified for
      several members of this disease family, genes underlying congenital facial
      paresis and Mobius syndrome remain to be discovered. Here we focus on HCFP linked
      to chromosome 3q21-q22 and identify new candidate genes using expression analysis
      by means of RNA in situ hybridization during mouse embryogenesis. We selected 28
      positional candidates and identified 17 genes with undetectable expression levels
      during mouse development, ubiquitous expression, or expression in tissues not
      affected in HCFP. Additionally, 7 genes were excluded by direct sequence or
      reverse transcription-PCR analysis. The remaining 4 genes (Klf15, Flj40083,
      Kiaa0779, and Podxl2) were found to be expressed at spatial and temporal
      positions during mouse development that correlate with HCFP regions in humans,
      defining these genes as primary candidates in HCFP.

PMID- 15953541
TI  - Identification and expression of a new type II transmembrane protein in human
      mast cells.
AB  - A cDNA encoding a new type II transmembrane protein has been isolated from human
      mast cells by subtraction cloning. This cDNA contains an open reading frame of
      186 amino acids. RT-PCR analysis showed that this gene is differentially
      expressed in mast cells. Therefore, the peptide encoded by this gene was termed
      mast cell-expressed membrane protein 1 (MCEMP1). The MCEMP1 gene contains seven
      exons and was mapped to human chromosome 19p13.3. The epitope-tagged MCEMP1 has
      been expressed in mammalian cells and found to be localized to the cellular
      membrane with its C-terminus extending to the outside of the membrane and N
      terminus into the cytoplasmic compartment. Monoclonal antibodies against MCEMP1
      were generated and characterized by immunoprecipitation and FACS. The results
      showed that the native MCEMP1 is expressed in cord blood-derived mast cells and
      HMC-1 and THP-1 cell lines, but not in other cell types that we have tested.
      Immunochemical staining of human lung sections showed that MCEMP1 staining is
      specifically associated with lung mast cells.

PMID- 15953542
TI  - Association of polymorphisms in CYP17A1, MTP, and VLDLR with bone mineral density
      in community-dwelling Japanese women and men.
AB  - We examined whether a -34T --> C polymorphism of the gene for cytochrome P450,
      family 17, subfamily A, polypeptide 1 (CYP17A1), a -493G --> T polymorphism of
      the microsomal triglyceride transfer protein gene (MTP), and a CGG repeat
      polymorphism of the very low density lipoprotein receptor gene (VLDLR) were
      associated with bone mineral density (BMD) in community-dwelling Japanese women
      and men. The -34T --> C polymorphism of CYP17A1 was associated with BMD in
      postmenopausal women, with the CC genotype being related to increased BMD. The 
      493G --> T polymorphism of MTP was associated with BMD in premenopausal women,
      with the TT genotype being related to increased BMD. The CGG repeat polymorphism
      of VLDLR was associated with BMD in men, with two (CGG)(n > or= 8) alleles being
      related to increased BMD. These results suggest that CYP17A1 and MTP are
      susceptibility loci for increased BMD in postmenopausal and premenopausal
      Japanese women, respectively, and that VLDLR constitutes such a locus in Japanese
      men.

PMID- 15953543
TI  - Expression analysis of SIX3 and SIX6 in human tissues reveals differences in
      expression and a novel correlation between the expression of SIX3 and the genes
      encoding isocitrate dehyhrogenase and cadherin 18.
AB  - SIX3 and SIX6 are transcription factors expressed during early stages of eye
      development. Limited expression data for SIX3 and SIX6 are available in the
      literature but, to date, there are no reports of the relative levels of
      expression of these genes throughout the human body and in adult tissues in
      particular. In this paper, we report extensive real-time quantitative PCR
      analyses of SIX3 and SIX6 expression in many different tissues of the adult human
      body, including ocular tissues, and a comparison of expression data with that of
      many other genes to identify similarity in expression. Using this powerful
      technique, we have detected a novel statistical correlation between the spatial
      distribution and the quantitative expression of SIX3 and 5 other transcripts
      including IDH1, the gene encoding the NADP(+)-dependent enzyme isocitrate
      dehydrogenase, and cadherin 18, type 2 (CDH14). Our data demonstrate that this
      novel technique can be used to generate hypotheses by comparison of gene
      expression profiles to identify possible interactions between genes or gene
      products.

PMID- 15953544
TI  - The complete complement of C1q-domain-containing proteins in Homo sapiens.
AB  - The C-terminal domains of the A, B, C chains of C1q subcomponent of C1 complex
      represent a common structural motif, the C1q domain, that is found in a diverse
      range of proteins. We analyzed the human genome for the complete complement of
      this family and have identified a total of 31 independent gene sequences. The
      predominant organization of C1q-domain-containing (C1qDC) proteins includes a
      leading signal peptide, a collagen-like region of variable length, and a C
      terminal C1q domain. There are 15 highly conserved residues within the C1q
      domain, among which 8 are invariant within the human gene set and these are
      predicted to cluster within the hydrophobic core of the protein. We suggest a 3
      subfamily classification based on sequence homology. For some C1qDC-encoding
      genes, strict orthology has been retained throughout vertebrate evolution and
      these examples suggest a highly specific functional role for C1qDC proteins that
      has been under significant selective pressure. Alternatively, individual species
      have co-opted C1qDC proteins for roles that are highly specific to their biology,
      suggesting an evolutionary strategy of gene duplication and functional
      diversification. A more extensive analysis of the evolutionary relationship of
      C1qDC proteins reveals an ancient rooting, with clear members found in
      eubacterial species. Curiously, we have been unable to identify C1qDC-encoding
      genes in many eukaryotic genomcs, such as Sacchromyces cerivisae and C. elegans,
      suggesting that the retention or loss of this gene family throughout evolution
      has been sporadic.

PMID- 15953545
TI  - Life support: the alpha4 phosphatase subunit in cell survival and apoptosis.
AB  - Reversible protein phosphorylation represents a cellular response to normal
      physiological processes as well as to cellular insults and stress. Recently, the
      protein phosphatase-associated alpha4 subunit was shown to be required for
      sustaining cell survival. Lack of alpha4 leads to apoptotic death of multiple
      cell types and to the death of the organism. Here, we explore how the phosphatase
      network might operate in controlling life-and-death decisions. We discuss the
      relevance of the findings for understanding the action of alpha4 in cell survival
      and for better discriminating between a role in maintaining cellular homeostasis,
      and thus survival, or actively keeping apoptotic cell death in check by targeting
      effectors of the cell death machinery.

PMID- 15953546
TI  - How dynein helps the cell find its center: a servomechanical model.
AB  - Cytoplasmic dynein is the major minus-end-directed microtubule motor protein in
      interphase cells. In addition to its well-established roles in vesicular
      transport and chromosome dynamics, cytoplasmic dynein also associates with the
      cell cortex. From this site, it appears to pull on the cytoplasmic microtubule
      network, influencing mitotic spindle orientation, nuclear position and other
      aspects of cell polarity and organization. Recent evidence indicates that the
      cell has the remarkable ability to calculate is geometric center, and, with the
      help of dynein, to position the centrosome at this central site. Here, we outline
      models to account for this behavior.

PMID- 15953547
TI  - MSI1-like proteins: an escort service for chromatin assembly and remodeling
      complexes.
AB  - MSI1-like WD40 repeat proteins are subunits of many protein complexes controlling
      chromatin dynamics. These proteins do not have any catalytic activity, but
      several recent studies using loss-of-function mutants established specific
      functions during development. Here, we review the current knowledge of MSI1-like
      proteins, including their phylogenetic history, expression patterns, biochemical
      interactions and mutant phenotypes. MSI1-like proteins, which are often targets
      or partners of tumor-suppressor proteins, are required during cell proliferation
      and differentiation in flies, nematodes and plants. We discuss the possibility
      that MSI1-like proteins could function to maintain epigenetic memory during
      development by targeting silencing complexes to chromatin during nucleosome
      assembly.

PMID- 15953548
TI  - Centrosome control of the cell cycle.
AB  - Early observations of centrosomes, made a century ago, revealed a tiny dark
      structure surrounded by a radial array of cytoplasmic fibers. We now know that
      the fibers are microtubules and that the dark organelles are centrosomes that
      mediate functions far beyond the more conventional role of microtubule
      organization. More recent evidence demonstrates that the centrosome serves as a
      scaffold for anchoring an extensive number of regulatory proteins. Among these
      are cell-cycle regulators whose association with the centrosome is an essential
      step in cell-cycle control. Such studies show that the centrosome is required for
      several cell-cycle transitions, including G(1) to S-phase, G(2) to mitosis and
      metaphase to anaphase. In this review (which is part of the Chromosome
      Segregation and Aneuploidy series), we discuss recent data that provide the most
      direct links between centrosomes and cell-cycle progression.

PMID- 15953549
TI  - The ins and outs of sphingolipid synthesis.
AB  - Sphingolipids are ubiquitous components of eukaryotic cell membranes, where they
      play important roles in intracellular signaling and in membrane structure. Even
      though the biochemical pathway of sphingolipid synthesis and its
      compartmentalization between the endoplasmic reticulum and Golgi apparatus have
      been known for many years, the molecular identity of the enzymes in this pathway
      has only recently been elucidated. Here, we summarize progress in the
      identification and characterization of the enzymes, the transport of ceramide
      from the endoplasmic reticulum to the Golgi apparatus, and discuss how regulating
      the synthesis of sphingolipids might impact upon their functions.

PMID- 15953550
TI  - Complex cellular responses to reactive oxygen species.
AB  - Genome-wide analyses of yeast provide insight into cellular responses to reactive
      oxygen species (ROS). Many deletion mutants are sensitive to at least one ROS,
      but no one oxidant is representative of 'oxidative stress' despite the widespread
      use of a single compound such as H(2)O(2). This has major implications for
      studies of pathological situations. Cells have a range of mechanisms for
      maintaining resistance that involves either induction or repression of many genes
      and extensive remodeling of the transcriptome. Cells have constitutive defense
      systems that are largely unique to each oxidant, but overlapping, inducible
      repair systems. The pattern of the transcriptional response to a particular ROS
      depends on its concentration, and 'classical' antioxidant systems that are
      induced by high concentrations of ROS can be repressed when cells adapt to low
      concentrations of ROS.

PMID- 15953551
TI  - Ral GTPases: corrupting the exocyst in cancer cells.
AB  - The Ras-like small G-proteins RalA and RalB have achieved some notoriety as
      components of one of a growing variety of candidate Ras effector pathways. Recent
      work has demonstrated that Ral GTPase activation is required to support both the
      initiation and maintenance of tumorigenic transformation of human cells. The
      mechanistic basis for this support remains to be defined. However, the discovery
      that the exocyst is a direct effector complex for activated Ral proteins suggests
      that mobilization of polarized exocytosis might be a basic component of the
      biological framework supporting tumorigenic progression.

PMID- 15953552
TI  - Tropomyosin isoforms: divining rods for actin cytoskeleton function.
AB  - Actin filament functional diversity is paralleled by variation in the composition
      of isoforms of tropomyosin in these filaments. Although the role of tropomyosin
      is well understood in skeletal muscle, where it regulates the actin-myosin
      interaction, its role in the cytoskeleton has been obscure. The intracellular
      sorting of tropomyosin isoforms indicated a role in spatial specialization of
      actin filament function. Genetic manipulation and protein chemistry studies have
      confirmed that these isoforms are functionally distinct. Tropomyosins differ in
      their recruitment of myosin motors and their interaction with actin filament
      regulators such as ADF-cofilin. Tropomyosin isoforms have therefore provided a
      powerful mechanism to diversify actin filament function in different
      intracellular compartments.

PMID- 15953553
TI  - Intrastrand base-stacking buttresses widening of major groove in interstrand
      cross-linked B-DNA.
AB  - The introduction of a covalent interstrand cross-link induces changes in the
      intrinsic structure and deformability of the DNA helix that are recognized by
      elements of the DNA repair apparatus. In this context, the solution structure of
      the undecamer d(CGAAAT*TTTCG)2, where T* represents a N3T-butyl-N3T interstrand
      cross-link, was determined using molecular dynamics calculations restrained by
      NOE and dihedral angle data obtained from NMR spectroscopy. The structure of this
      cross-linked undecamer shows dramatic widening of the major groove of the B-DNA
      stem without disruption of Watson-Crick base pairing. This change in tertiary
      structure illustrates the cumulative effect of cooperativity in intrastrand base
      stacking of an A-tract of three adenines. Further, it is the direct result from
      the imposition of geometric angular constraints by the cross-link chain on an
      ApT* and T*pT steps in the segment AAAT*T. The widening of the major groove is
      due to the dominant contribution of base stacking to the stability of the ApT
      compared to the TpT step suggesting that the latter is more deformable within a
      DNA stem. Compared to earlier structures of ethyl cross-linked oligonucleotides,
      this unique perturbation induced by the butyl moiety offers a new probe for
      systematic studies of DNA repair mechanisms.

PMID- 15953554
TI  - Expression of MCT1, MCT2 and MCT4 in the rumen, small intestine and liver of
      reindeer (Rangifer tarandus tarandus L.).
AB  - The expression of monocarboxylate transporters MCT1, MCT2 and MCT4 in the rumen,
      small intestine and liver was examined in free-ranging and captive reindeer. In
      addition, expression of chaperone protein CD147, which is needed for the activity
      of MCT1 and MCT4, was studied in the rumen of suckling calves. Immunoblotting of
      cell membrane proteins showed the expression of MCT1 and MCT4, but not that of
      MCT2 in the rumen of reindeer. In free-ranging reindeer the amount of MCT1 was
      higher than in the captive ones (P<0.01). Developing rumen of suckling calves
      expressed MCT1 and MCT4 and positive correlation was found between MCT1 and
      CD147. Both MCT1 and CD147 correlated also with age in calves less than 10 days.
      In the small intestine all the isoforms studied were expressed, but the amounts
      were lower than in the rumen (P<0.05). In the liver MCT1 and MCT2 were found
      while MCT4 was nearly undetectable. The expression of MCT isoforms in the rumen
      and small intestine reflects the site of absorption and concentrations of short
      chain fatty acids (SCFA). In the liver the expression of high affinity
      transporters, MCT1 and MCT2, is in accordance with almost complete uptake of
      propionate from portal blood.

PMID- 15953555
TI  - Infraslow EEG activity in burst periods from post asphyctic full term neonates.
AB  - OBJECTIVE: To investigate whether very low EEG frequency activity can be recorded
      from post asphyctic full term neonates using EEG equipment where the high pass
      filter level was lowered to 0.05 Hz. METHODS: The time constant of the amplifier
      hardware was set to 3.2 s in order to enable recordings that equal to a high pass
      filter cut off at 0.05 Hz. Burst episodes were selected from the EEGs of 5 post
      asphyctic full term neonates. The episodes were analysed visually using different
      montages and subjected to power spectrum analysis. Powers in two bands were
      estimated; 0-1 and 1-4 Hz, designated very low- and low-frequency activity,
      respectively (VLFA, LFA). RESULTS: In all infants, VLFA coinciding with the burst
      episodes could be detected. The duration of the VLFA was about the same as that
      of the burst episode i.e. around 4s. The activity was most prominent over the
      posterior regions. In this small material, a large amount of VLFA neonatally
      seemed to possibly be related to a more favourable prognosis. CONCLUSIONS: VLFA
      can be recorded from post asphyctic full term neonates using EEG equipment with
      lowered cut off frequency for the high pass filter. SIGNIFICANCE: VLFA normally
      disregarded due to filtering, is present in the EEG of sick neonates and may
      carry important clinical information.

PMID- 15953556
TI  - Movement preparation is affected by tissue damage in multiple sclerosis: evidence
      from EEG event-related desynchronization.
AB  - OBJECTIVE: To investigate the impact of brain tissue damage in Multiple Sclerosis
      (MS) on the efficiency of programming of voluntary movement, assessed using event
      related desynchronization of the EEG. METHODS: The onset latency of mu ERD
      (percent desyncronization of the mu rhythm preceding movement onset) to hand
      movement was studied in 34 MS patients. ERD onset was compared with normative
      data and correlated with T1 and T2 total lesion volume (TLV) at magnetic
      resonance imaging (MRI). RESULTS: ERD onset latency was significantly correlated
      with T1-TLV (r = 0.53, P = 0.001) and T2 lesion load (r = 0.5, P = 0.003), even
      after correcting for disability. Patients with higher T1-TLV had significantly
      delayed ERD onset compared with normal subjects and with patients with lower T1
      TLV; patients with higher T2-TLV had significantly delayed ERD compared with
      normal subjects only. ERD onset latency was not correlated to clinical
      disability. CONCLUSIONS: Our finding of delayed ERD onset in patients with more
      severe measures of brain damage, independently from clinical disability, suggests
      that functional cortico-cortical and cortico-subcortical connections underlying
      the expression of ERD during programming of voluntary movement are disrupted by
      the MS related pathological process. Further, studies are needed to evaluate the
      role of specific anatomical cortico-subcortical circuits in determining this
      abnormality. SIGNIFICANCE: The extent of brain lesion load in multiple sclerosis
      affects cortical changes related to motor preparation, detected by analysis of
      onset latency of event-related desynchronization (ERD) of the mu rhythm to self
      paced movement.

PMID- 15953557
TI  - The relationship between ictal activity and sleep stages in the newborn EEG.
AB  - OBJECTIVE: To verify the relationship of ictal activity and sleep organization
      (REM/NREM stages) in the neonatal EEG. METHODS: A retrospective study was
      developed with 41 high-risk newborns, with clinical history suggestive of
      seizures and ictal activity identified by the EEG. In each EEG, sleep
      organization and number/duration of sleep stages were determined. Sleep stages
      (REM, NREM) were scored following behavior and EEG activity. When it was
      impossible to recognize stages the epoch was classified as unrecognizable sleep
      stages (UNSS). Ictal activity was classified according to morphology and
      correlated with sleep epochs. Density of ictal activity was calculated as the
      duration of the discharge divided by the duration of the sleep epoch. RESULTS:
      Unrecognizable sleep stages were observed in 21 EEGs (51.2%). Comparing NREM X
      REM states there was a significant predominance of ictal activity in REM sleep (P
      = 0.01). Duration of discharges was longer on REM epochs; however, differences
      were not significant. Considering the type of discharges there was a predominance
      of monomorphic rhythmic discharges in all sleep epochs. CONCLUSIONS: In this
      sample, epileptogenic activity occurred more frequently in UNSS, where sleep
      organization was already disrupted. When it was possible to recognize sleep
      stages, ictal activity was more frequently during REM sleep. SIGNIFICANCE: This
      study speculates the relationship between sleep organization and ictal activity
      and raises the hypothesis that the expression of ictal activity in relation to
      sleep stages (REM/NREM) may have age-dependent mechanisms in the developing
      brain.

PMID- 15953558
TI  - Excitability of facial nucleus and related brain-stem reflexes in hemifacial
      spasm, post-facial palsy synkinesis and facial myokymia.
AB  - OBJECTIVE: To compare the electrophysiological excitability characteristics of
      the facial nucleus and related structures in hemifacial spasm (HFS), post-facial
      palsy synkinesis (PFPS) and facial myokymia (FM). METHODS: Facial F-waves, blink
      reflex recoveries and magnetically elicited silent periods (SP) were
      prospectively studied in 17 HFS, 17 PFPS, 8 FM cases and in 13 controls. Earlier
      unpublished observations on abnormal impulse transmission in 36 HFS and 29 PFPS
      cases were also included. RESULTS: Enhanced F-waves were recorded on the
      symptomatic side in PFPS and HFS cases with a tendency to be more pronounced in
      PFPS. HFS and PFPS groups both showed an earlier blink reflex recovery, more
      prominent in PFPS patients, when stimulated and/or recorded on the symptomatic
      side. Unelicitable SPs were encountered after 24/39 stimulations in 5 patients
      with PFPS and rarely in HFS cases. Duration of elicitable SPs did not change
      remarkably. FM group had similar characteristics as normal controls in the 3
      electrophysiological tests. Latencies of the lateral and synkinetic spread
      responses were significantly prolonged in the earlier PFPS group as compared to
      HFS. In two-point stimulation, both groups showed a greater latency shift in late
      responses, again more pronounced in PFPS. CONCLUSIONS: PFPS and HFS cases had
      similar enhanced excitability patterns at the facial nucleus and related brain
      stem structures, more marked on the symptomatic side and more obvious in the PFPS
      group. Findings elicited in the FM group were thought to be caused by
      asynchronous hyperactivity of facial motoneurons. SIGNIFICANCE: In this
      comparative electrophysiological study, similar excitability patterns were found
      in HFS and PFPS groups, albeit with different intensities.

PMID- 15953559
TI  - Functional magnetic resonance imaging and transcranial magnetic stimulation:
      effects of motor imagery, movement and coil orientation.
AB  - OBJECTIVE: To compare fMRI activations during movement and motor imagery to
      corresponding motor evoked potential (MEP) maps obtained with the TMS coil in
      three different orientations. METHODS: fMRI activations during executed (EM) and
      imagined (IM) movements of the index finger were compared to MEP maps of the
      first dorsal interosseus (FDI) muscle obtained with the TMS coil in anterior,
      posterior and lateral handle positions. To ensure spatial registration of fMRI
      and MEP maps, a special grid was used in both experiments. RESULTS: No
      statistically significant difference was found between the TMS centers of gravity
      (TMS CoG) obtained with the three coil orientations. There was a significant
      difference between fMRI centers of gravity during IMs (IM CoG) and EMs (EM CoG),
      with IM CoGs localized on average 10.3mm anterior to those of EMs in the
      precentral gyrus. Most importantly, the IM CoGs closely matched cortical
      projections of the TMS CoGs while the EM CoGs were on average 9.5mm posterior to
      the projected TMS CoGs. CONCLUSIONS: TMS motor maps are more congruent with fMRI
      activations during motor imagery than those during EMs. These findings are not
      significantly affected by changing orientation of the TMS coil. SIGNIFICANCE: Our
      results suggest that the discrepancy between fMRI and TMS motor maps may be
      largely due to involvement of the somatosensory component in the EM task.

PMID- 15953560
TI  - Effect of experimental posterior temporalis muscle pain on human brainstem
      reflexes.
AB  - OBJECTIVE: To study the modulation of jaw-stretch and blink reflexes by
      experimental posterior temporalis muscle pain. METHODS: Thirty healthy volunteers
      (15 males, 25.5+/-0.6 years and 15 females, 27.4 +/- 1.2 years) were included.
      Short-latency stretch reflex responses were evoked in the masseter and temporalis
      muscles by fast stretches (1 mm displacement, 10 ms ramp time) and the blink
      reflexes were evoked by painful electrical pulses (0.5 ms duration), delivered by
      a concentric electrode placed on the left lower forehead close to the
      supraorbital foramen before, during and 15 min after a period with experimentally
      induced muscle pain. RESULTS: The normalized peak-to-peak amplitude of the
      stretch reflex in the painful temporalis was significantly higher during pain in
      both males and females compared with pre- and post-pain conditions (P < 0.004).
      The R2 root mean square (RMS) of the blink reflex decreased significantly during
      muscle pain as compared to the pre-pain (P < 0.03) in both males and females.
      CONCLUSIONS: The present results indicated that experimental posterior temporalis
      muscle pain facilitates the jaw-stretch reflex, whereas the nociceptive specific
      blink reflex is inhibited. SIGNIFICANCE: Present study suggested that these
      reflexes are suitable models for probing pontine and medullary pain processing.

PMID- 15953561
TI  - Distinct contrast response functions in striate and extra-striate regions of
      visual cortex revealed with magnetoencephalography (MEG).
AB  - OBJECTIVE: To spatially and temporally characterise the cortical contrast
      response function to pattern onset stimuli in humans. METHODS:
      Magnetoencephalography (MEG) was used to investigate the human cortical contrast
      response function to pattern onset stimuli with high temporal and spatial
      resolution. A beamformer source reconstruction approach was used to spatially
      localise and identify the time courses of activity at various visual cortical
      loci. RESULTS: Consistent with the findings of previous studies, MEG beamformer
      analysis revealed two simultaneous generators of the pattern onset evoked
      response. These generators arose from anatomically discrete locations in striate
      and extra-striate visual cortex. Furthermore, these loci demonstrated notably
      distinct contrast response functions, with striate cortex increasing
      approximately linearly with contrast, whilst extra-striate visual cortex followed
      a saturating function. CONCLUSIONS: The generators that underlie the pattern
      onset visual evoked response arise from two distinct regions in striate and extra
      striate visual cortex. SIGNIFICANCE: The spatially, temporally and functionally
      distinct mechanisms of contrast processing within the visual cortex may account
      for the disparate results observed across earlier studies and assist in
      elucidating causal mechanisms of aberrant contrast processing in neurological
      disorders.

PMID- 15953562
TI  - Long-term exacerbation by interleukin 13 of IgE-mediated eosinophilia in rats.
AB  - Recent work shows that at least two cycles of antigen challenge applied in a 7
      day interval are required to yield tissue eosinophil accumulation in IgE
      passively sensitized rats. Since interleukin (IL)-13 is widely regarded as a key
      mediator in eosinophilic responses associated with mast cells and IgE, we
      investigated whether this cytokine could replace the first cycle of sensitization
      and challenge in its proeosinophilic role. We found that IL-13 (25 and 50
      ng/cavity) injected into the rat pleural space led to eotaxin generation and a
      dose-dependent accumulation of eosinophils following IgE-passive sensitization
      and challenge 7 days later. IL-13 failed to cause eosinophil chemotaxis in vitro
      but induced eosinophil accumulation into the pleural cavity of naive rats, which
      peaked 1 day and faded 72 h post-challenge. No changes were found 1 week after
      intrapleural injection of IL-13, except an approximately 40-50% increase in the
      number of adhered and non-adhered pleural mast cells. As recovered from the
      pleural effluent 1 week after IL-13, mast cells expressed the same amount of IgE
      bound on their surface as compared to controls. However, they generated 3-fold
      more LTC(4) following IgE-sensitization and challenge in vitro, keeping intact
      the amount of histamine released. Finally, pretreatment with zileuton (50
      microg/cavity) 1 h before allergen challenge prevented eosinophil accumulation in
      those animals injected with IL-13 1 week before. In conclusion, our findings show
      that IL-13 causes a long-term exacerbation of the IgE-mediated eosinophilic
      response in a mechanism associated with heightened cysteinyl-leukotriene (cys-LT)
      production by resident mast cells.

PMID- 15953563
TI  - Suppressive effect of AIF, a water extract from three herbs, on collagen-induced
      arthritis in mice.
AB  - AIF has been formulated using three herbs known to have anti-inflammatory and
      anti-osteolytic effects. In this study, the potential therapeutic effects of AIF
      for rheumatoid arthritis were assessed in vitro and in vivo. The effects of AIF
      on the inflammation (TNF-alpha, IL-1, iNO), cartilage protection (MMP-13), and
      selective killing of activated T cells were examined, in vitro. In addition, the
      therapeutic effect of AIF was evaluated using a collagen-induced arthritis (CIA)
      mouse model. DBA/1 mice were immunized with type II collagen. Following booster
      immunization, mice were treated with the oral administration of 276 mg/kg/d AIF
      once a day for 18 days, then, the severity of CIA was evaluated by macroscopic
      scoring and histopathological assessment. AIF significantly inhibited the
      production of TNF-alpha, IL-1, iNO, and MMP-13 in a dose dependent manner in
      vitro. Also, AIF killed activated T cells selectively, conserving naive T cells.
      The oral administration of AIF in CIA mice suppressed the progression of CIA
      significantly and decreased synovial hyperplasia, cartilage destruction, and bone
      erosion. AIF showed potent anti-inflammatory effects in vitro and substantial
      protective effect for the progression of CIA in vivo. These results suggest that
      AIF contains effective compound(s) which may modify the progression of rheumatoid
      arthritis.

PMID- 15953564
TI  - A possible signal transduction pathway for cyclin D2 expression by a pectic
      polysaccharide from the roots of bupleurum falcatum L. in murine B cell.
AB  - Bupleuran 2IIc, a pectic polysaccharide isolated from the roots of bupleurum
      falcatum L., was previously characterized as a T-cell-independent B cell mitogen.
      This study focuses on elucidating the mechanism by which bupleuran 2IIc induces
      cyclin D2 production for inducing mitogenesis in murine B cells. Bupleuran 2IIc
      was digested with endo-alpha-(1-->4)-D-polygalacturonase and the resulting
      bupleuran 2IIc/PG-1 ("ramified" region) strongly stimulated cyclin D2 expression.
      When murine B cells were stimulated with bupleuran 2IIc/PG-1, phosphorylation of
      tyrosine residues of a number of proteins was observed. Cyclin D2 expression by
      bupleuran 2IIc/PG-1 was inhibited by the tyrosine kinase inhibitors, genistein
      and herbimycin A, and the Src family tyrosine kinase inhibitor, PP2, suggesting a
      possible role for tyrosine kinases. The stimulation by bupleuran 2IIc/PG-1 of
      cyclin D2 expression was significantly decreased by inhibitors, PI 3-kinase
      (LY294002 and Wortmannin), PLCgamma (U73122), PKC (H-7), receptor-operated
      calcium entry inhibitor (SK&F 96365), and calcineurin (FK506). Both PD98059 and
      U0126, highly selective inhibitors of MEK1 and MEK1/2, respectively, did not
      strongly suppress the expression of cyclin D2 after stimulation by bupleuran
      2IIc/PG-1. The results suggest that (1) bupleuran 2IIc/PG-1 is the active site
      for induction of cyclin D2 by bupleuran 2IIc, (2) the expression of the cyclin D2
      gene by bupleuran 2IIc/PG-1 may be mediated via the activation of PI 3-kinase and
      PLCgamma followed by activation of PKC and calcium mobilization, and (3) the
      ERK1/2 cascade is not a central signaling pathway for bupleuran 2IIc/PG-1-induced
      cyclin D2 expression.

PMID- 15953565
TI  - Protective effect of beta-glucan against oxidative organ injury in a rat model of
      sepsis.
AB  - Sepsis leads to various organ damage and dysfunction. One of the underlying
      mechanisms is thought to be the oxidative damage due to the generation of free
      radicals. In this study, we investigated the putative protective role of beta
      glucan against sepsis-induced oxidative organ damage. Sepsis was induced by
      caecal ligation and puncture (CLP) in Wistar albino rats. Sham operated (control)
      and sepsis groups received saline or beta-glucan (50 mg/kg, po) once daily for 10
      days and 30 min prior to and 6 h after the CLP. Sixteen hours after the surgery,
      rats were decapitated and the biochemical changes were determined in the brain,
      diaphragm, kidney, heart, liver and lung tissues using malondialdehyde (MDA)
      content - an index of lipid peroxidation - glutathione (GSH) levels - a key
      antioxidant - and myeloperoxidase (MPO) activity - an index of neutrophil
      infiltration. Serum TNF-alpha levels were assessed by RIA method. Tissues were
      also examined under light microscope to evaluate the degree of sepsis-induced
      damage. The results demonstrate that sepsis significantly decreased GSH levels
      and increased the MDA levels and MPO activity (p<0.05-p<0.001) causing oxidative
      damage. Elevated plasma TNF-alpha levels in septic rats significantly reduced to
      control levels in beta-glucan treated rats. Since beta-glucan administration
      reversed these oxidant responses, it seems likely that beta-glucan protects
      against sepsis-induced oxidative organ injury.

PMID- 15953566
TI  - Protective role of melatonin in cyclosporine A-induced oxidative stress in rat
      liver.
AB  - Cyclosporine A (CsA) is the most widely used immunosuppressive drug for
      preventing graft rejection and autoimmune disease. However, the therapeutic
      treatment induces several side effects such as nephrotoxicity, cardiotoxicity,
      hypertension and hepatotoxicity. Among possible mechanisms of CsA-induced hepatic
      damage, oxidative stress has been suggested. Melatonin (Mel) has been
      successfully used as a potent antioxidant against many pathophysiological states.
      This experimental study was performed to test, during CsA treatment, the
      alterations of some heat shock proteins (HSP) and the Mel antioxidant properties
      against CsA-induced injury. Rats were divided into four groups, which were
      treated respectively with olive oil, Mel alone, CsA and CsA plus Mel for 30 days.
      At the end of the treatments, the animals were killed and hepatic tissue was
      treated for morphological (haematoxylin-eosin), biochemical (reduced glutathione,
      GSH and malondialdehyde, MDA) and immunohistochemical (HSP60, HSP72, GRP75 and
      MT) analyses. The results indicate that CsA-induced hepatotoxicity was
      characterised by morphological alterations in tissue architecture, changes in GSH
      and MDA levels and increase in stress protein expression. In conclusion, our data
      suggest that the imbalance between production of free oxygen radicals and
      antioxidant defence systems, due to CsA administration, is a mechanism
      responsible for oxidative stress. Moreover, we show that Mel plays a protective
      action against CsA-induced oxidative stress, as supported by biochemical and
      immunohistochemical results.

PMID- 15953567
TI  - Bee venom modulates murine Th1/Th2 lineage development.
AB  - Administration of bee venom (BV) elicits anti-inflammatory, anti-nociceptive and
      anti-allergic effects in various animal models. This study was designed to
      evaluate the direct effects of BV on helper T cell activities and on Th1/Th2
      lineage development using both in vitro and in vivo conditions. In the Th1 skewed
      condition, BV increased the expression of IFN-gamma mRNA and enhanced the
      expression of T-bet on purified CD4(+) T cells from splenocytes of BALB/c mice.
      On the other hand, BV treatment did not alter the expression of IL-4 or GATA-3 in
      a Th2 driven environment. To elucidate the effects of BV on Th1/Th2 lineage
      development under in vivo conditions, BV was given by intraperitonial injection
      to BALB/c mice. It significantly increased the CD4(+) T cell population and
      enhanced IFN-gamma expression, while IL-4 transcripts were not altered upon in
      vivo activation using an anti-CD3 antibody injection. Taken together, these
      results imply that BV induces Th1 lineage development from CD4(+) T cells by
      increasing the expression of a Th1-specific cytokine, IFN-gamma. In addition,
      this result may be mediated by inducing a Th1-specific transcription factor, T
      bet.

PMID- 15953568
TI  - Triptolide affects the differentiation, maturation and function of human
      dendritic cells.
AB  - Triptolide is a purified component from a traditional Chinese herb Tripterygium
      wilfordii Hook F. It has been shown to have anti-inflammatory and
      immunosuppressive activities by its inhibitory effect on T cells. But the effect
      of triptolide on dendritic cells (DC) is unknown. Dexamethasone (Dex) is a
      classic immunosuppressive agent known to suppress the immune response at
      different levels and has recently found to modulate the development of DC,
      thereby influencing the initiation of the immune response. In this study, we
      investigated the affect of triptolide on the differentiation, maturation and
      function of DC differentiated from human monocytes (MoDC) in vitro in the
      presence of GM-CSF and IL-4. Dex was included in the study as a reference. Our
      data show that both triptolide and Dex prevented the differentiation in immature
      MoDC by inhibiting CD1a, CD40, CD80, CD86 and HLA-DR expression but upregulating
      CD14 expression, as well as by reducing the capacity of MoDC to stimulate
      lymphocyte proliferation in the allogeneic mixed lymphocyte reaction. They
      blocked the maturation of MoDC as totally blocked induction of CD83 expression
      and absent upregulation of CD40, CD80, CD86 and HLA-DR. In addition, higher
      concentration of triptolide (20 ng/ml) and 10(-6) M Dex induced apoptosis in MoDC
      as measured by expression of APO2*7 and DNA fragmentation (TUNEL assay). However,
      the phagocytic capacity of MoDC was enhanced by triptolide but not Dex.
      Therefore, the suppression of DC differentiation, the function in immature DCs as
      well as the inhibition of DC maturation by triptolide may explain some of its
      immunosuppressive properties. It is suggested that DCs are a primary target of
      the immunosuppressive activity of triptolide.

PMID- 15953569
TI  - Peanut-lupine antibody cross-reactivity is not associated to cross-allergenicity
      in peanut-sensitized mouse strains.
AB  - BACKGROUND: Peanut hypersensitivity is one of the most common food allergies and
      one of the most common causes of death by food anaphylaxis in children and
      adults. Cross-reactivity of peanut-specific antibody (Ab) with other legumes is
      frequently demonstrated but it still remains to be demonstrated whether these
      responses could lead to clinical signs of cross-allergenicity. OBJECTIVE: We
      sought to evaluate peanut-specific serum IgE and IgG1 antibody (Ab) responses and
      anaphylactic reaction in mice strains and to assess both cross-reactivity and
      cross-allergenicity of peanut and lupine. METHODS: Four mice strains (i.e., C3H,
      BALB/c, CBA and SJL) were sensitized to peanut by intraperitoneal (ip) injection
      of crude peanut protein extract with alum. Other groups were given oral peanut
      extract without adjuvant. Peanut-specific antibodies (Abs) and anaphylactic
      responses to peanut challenge were examined. RESULTS: The C3H, CBA (H-2(k)) and
      BALB/c (H2-(d)) mice exhibited high levels of peanut-specific serum IgE, IgG1 Ab
      responses after the intra-peritoneal sensitization. Only the two strains of mice
      in the H-2(k) background developed anaphylactic symptoms upon intra-peritoneal
      challenge with crude peanut protein extract. While cross-reactivity of peanut and
      lupine was confirmed by ELISA, no clinical symptom of cross-allergenicity was
      seen after challenge with lupine. Mice that were given oral peanut showed only
      increase in peanut-specific IgG2a, but no IgE or IgG1 Abs and failed to develop
      anaphylactic reactions following injection of either peanut or lupine protein.
      CONCLUSION: These results show that mice of different genetic backgrounds can be
      sensitized to peanut by ip injection to develop anti-peanut Abs that cross react
      with lupine. In addition, cross-allergenicity may not directly correlate with the
      presence of cross-reactive Abs since no clinical symptoms of cross-allergenicity
      was seen after ip challenge with lupine.

PMID- 15953570
TI  - Characterization and immunostimulatory activity of an (1-->6)-a-D-glucan from the
      root of Ipomoea batatas.
AB  - The polysaccharide PSPP (purified sweet potato polysaccharide), isolated and
      purified from the roots of Ipomoea batatas, was found to be a glucan with a
      molecular weight of 53.2 kDa and specific rotation of +115.0 degrees (ca. 0.80,
      H(2)O). On the basis of methylation analysis, periodate oxidation, Smith
      degradation, infra-red spectroscopy, and (13)C NMR, the polysaccharide was
      confirmed as a (1-->6)-alpha-D-glucan. We evaluated the effects of polysaccharide
      PSPP on the in vivo immune function of mouse. Mice were treated with the
      polysaccharide PSPP (50, 150, and 250 mg/kg body weight) for 7 days. Phagocytic
      function, proliferation of lymphocytes, natural killer cell activity, hemolytic
      activity, and serum IgG concentration of the mice were studied. At the dose of 50
      mg/kg, significant increments in proliferation of lymphocytes (P<0.05) and serum
      IgG concentration (P<0.05) were observed. At the dose of 150 and 250 mg/kg,
      significant increments (P<0.01 or P<0.05) were observed in all tested
      immunological indexes. A dose-dependent manner was demonstrated in phagocytic
      function, hemolytic activity, and serum IgG concentration, but not in
      proliferation of lymphocytes and natural killer cell activity. This suggests that
      PSPP improve the immune system and could be regarded as a biological response
      modifier.

PMID- 15953571
TI  - Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial
      cells.
AB  - Previous studies have shown that sinomenine possesses potent immunoregulatory
      properties. However, little is known about its exact mechanisms of action.
      Increasing recognition of the importance of renal tubular epithelial cells (TECs)
      in renal diseases raises the question whether sinomenine can regulate TEC
      activity. In this study, cultured human TECs were exposed to proinflammatory
      factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha)
      in presence or absence of sinomenine for 72 h, followed by analysis of surface
      expression of costimulatory molecules. Flow cytometric analysis revealed that
      various costimulatory molecules were expressed on TECs and that they were
      significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However,
      sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both
      mRNA and protein levels. Moreover, the significant damping effect of sinomenine
      on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co
      cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs
      activity via B7-H1 and B7-DC, in addition to previously reported its effects on
      some pro-inflammatory factors production by macrophages and peripheral blood
      mononuclear cells.

PMID- 15953572
TI  - Action of prolactin, IFN-gamma, TNF-alpha and LPS on heme oxygenase-1 expression
      and VEGF release in human monocytes/macrophages.
AB  - The pituitary hormone prolactin (PRL) has recently been regarded as a local
      regulator of macrophage responses. Our goal in this study was to investigate the
      regulatory interaction between PRL, interferon-gamma (IFN-gamma), tumor necrosis
      factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) in the heme oxygenase-1 (HO
      1) expression and the vascular endothelial growth factor (VEGF) production in
      human monocytes/macrophages (HMMs). In vitro treatment of HMMs with PRL, IFN
      gamma, TNF-alpha and LPS was found to increase both HO-1 expression and protein
      synthesis in a time-dependent manner. HMMs treated with PRL, IFN-gamma, TNF-alpha
      and LPS also showed an enhanced release of VEGF. Moreover, co-stimulation of PRL
      with LPS caused activation of HMMs functions, enhancement of HO-1 expression and
      induction of VEGF release, whereas addition of PRL inhibited up-regulation of HO
      1 or VEGF induced by IFN-gamma or TNF-alpha. Our results demonstrate that PRL,
      IFN-gamma, TNF-alpha and LPS modulate the expression of angiogenic factors
      providing additional information about the regulatory mechanism, which controls
      the angiogenic function of macrophages.

PMID- 15953573
TI  - Novel lectins from rhizomes of two Acorus species with mitogenic activity and
      inhibitory potential towards murine cancer cell lines.
AB  - Two novel lectins were purified from rhizomes of two sweet flag species, namely
      Acorus calamus (Linn.) and Acorus gramineus (Solandin Ait.) by affinity
      chromatography on mannose linked epoxy-activated Sepharose 6B. The apparent
      molecular mass of the lectins, as determined by gel filtration chromatography,
      was 56 kDa for ACL and 55 kDa for AGL. In SDS-PAGE, pH 8.3, both lectins migrated
      with a subunit molecular mass of 13.6 kDa and 13.5 kDa, respectively, under
      reducing and non-reducing conditions thus indicating the absence of disulphide
      linkages. Acorus lectins readily agglutinated rabbit, rat and guinea pig
      erythrocytes. Both ACL and AGL also reacted with RBCs from sheep, goat and human
      ABO blood groups after neuraminidase treatment. ACL and AGL were inhibited by
      mannose/glucose and their derivatives. The most effective inhibitor was methyl
      alpha-D-mannopyranoside. Acorus lectins were stable up to 55 degrees C, did not
      require metal ions for their activity and were also affected by high
      concentrations of denaturants like urea, thiourea and guanidine-HCl. These
      lectins showed potent mitogenic activity towards mouse splenocytes and human
      lymphocytes. Both ACL and AGL also significantly inhibited the growth of J774, a
      murine macrophage cancer cell-line and to lesser extent WEHI-279, a B-cell
      lymphoma.

PMID- 15953574
TI  - Long-term hematological and immunological complications of sulfur mustard
      poisoning in Iranian veterans.
AB  - BACKGROUND: Sulfur mustard (SM) is an alkylating chemical warfare agent that was
      widely used during World War I and by Iraqi forces against Iranian soldiers. We
      aimed to study late toxic effects of SM on the blood and the immune system of
      severely intoxicated Iranian veterans. METHODS: All SM-poisoned veterans in the
      province of Khorasan, Iran who had severe clinical complications were studied.
      Blood cell count, flow cytometric analysis of immune cells, serum protein
      electrophoresis, and determination of serum immunoglobulins and complement
      components levels were performed for the patients and 35 healthy age-matched
      controls. Hematological and immunological parameters were compared between the
      patients and the control group, using Mann-Whitney U test. RESULTS: Forty male
      subjects (aged 43.8+/-9.8 years) who had confirmed SM poisoning 16 to 20 years
      prior to this study were investigated. Total counts for WBC and RBC, as well as
      Hct percentage were significantly (p<or=0.042) higher in the patients than in the
      controls. The percentages of monocytes and CD3(+) T-lymphocytes were
      significantly higher (p=0.013 and p=0.037, respectively) and the percentage of
      CD16+56 positive cells was significantly lower in patients (p=0.006). IgM and C3
      levels were significantly higher in patients (p<or=0.030). The absolute level of
      alpha(1) globulin, as well as absolute levels and the percentages of alpha(2) and
      beta globulins were significantly higher in patients compared to the control
      group (p<or=0.024). CONCLUSIONS: SM can cause long-term effects on the immune
      system in patients with severe intoxication. The impaired immunity is probably
      responsible for the increased risk of infections in these patients.

PMID- 15953575
TI  - Regional patterns of sight-threatening diabetic macular edema.
AB  - PURPOSE: To define regional patterns of macular thickening in diabetic macular
      edema (DME). DESIGN: Retrospective case series. METHODS:  SETTING: Retina
      practice. PATIENT POPULATION: Fifty-two normal eyes of 48 patients and 100 eyes
      of 80 patients with DME. EXPERIMENTAL PROCEDURE: We measured retinal thickness
      for nine zones and total macular volume using the 3.5-mm display of an optical
      coherence tomograph (OCT). We determined the normal ranges of values for zones,
      and then normal ranges of values for the difference in thickness between each
      pair of zones, termed comparisons. main outcome measures: Frequencies of
      increased zonal thickness, increased total macular volume, and abnormalities in
      zonal comparisons. RESULTS: We found the following abnormalities: increased total
      macular volume 49% (49/100), increased foveal zone thickness 46% (46/100),
      increased inner parafoveal zone thickness (average 42.2% for the four zones), and
      increased outer zone thickness (average 34.3% for the four zones). Abnormal two
      zone comparisons were found in 1027 of the 7200 possible comparisons (14.3%). Of
      these abnormal comparisons, the fovea was thicker relative to another zone in
      26%; the four inner parafoveal zones were thicker relative to other zones in 8.7%
      to 15.2% (average 13.0%); and the four outer zones were thicker relative to other
      zones in 3.9% to 7.6% (average 6%). Eighty-eight percent (88/100) of the eyes
      chosen on clinical grounds as needing focal laser photocoagulation were detected.
      CONCLUSION: A broader concept of OCT abnormality, which includes abnormalities in
      zonal relationships, may improve automated detection of DME compared with
      clinical judgment.

PMID- 15953576
TI  - Intravenous administration of L-arginine increases retinal and choroidal blood
      flow.
AB  - PURPOSE: Nitric oxide (NO) is among the most important regulators of ocular
      perfusion. L-arginine, an amino acid, is the precursor of NO synthesis. The aim
      of the present study was to determine whether administration of L-arginine
      affects ocular blood flow. DESIGN: L-arginine (1 g/min) or placebo was
      administered intravenously for 30 minutes in 12 healthy volunteers in a
      randomized, double-masked, two-way cross-over design. METHODS: Ocular
      hemodynamics were measured before, in the last 10 minutes of the infusion period,
      as well as 30 minutes after cessation of the administration. Retinal vessel
      diameters were measured with a retinal vessel analyzer, red blood cell velocities
      with bidirectional laser Doppler velocimetry, and pulsatile choroidal blood flow
      was measured using laser interferometry. RESULTS: L-arginine significantly
      decreased mean arterial pressure by -8 +/- 5% and -6 +/- 7% at the two time
      points (P < .01), respectively. Intravenous administration of L-arginine
      increased choroidal blood flow by +10 +/- 6% and +12 +/- 7%, respectively.
      Retinal venous diameters decreased by -2.5 +/- 2.1% and -1.4 +/- 2.7%,
      respectively, whereas red blood cell velocity significantly increased after
      administration of L-arginine by +22 +/- 23% and +20 +/- 19% at the two time
      points. Thus, calculated blood flow in retinal veins, increased by +21 +/- 18%
      and +21 +/- 19% before and after the end of L-arginine infusion. CONCLUSIONS:
      Intravenous administration of L-arginine increases retinal and choroidal blood
      flow in healthy volunteers. Whether this effect is related to an increased NO
      production or an unidentified mechanism remains to be clarified. However,
      administration of L-arginine might be an interesting new approach to
      therapeutically increase ocular blood flow in ocular vascular disease.

PMID- 15953577
TI  - The effect of fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on
      epithelial healing following photorefractive keratectomy.
AB  - PURPOSE: To compare the rate of epithelial healing following photorefractive
      keratectomy (PRK) with two commercially available fourth-generation
      fluoroquinolones, gatifloxacin (Zymar, Allergan, Irvine, California) and
      moxifloxacin (Vigamox, Alcon Laboratories, Fort Worth, Texas). DESIGN: Double
      masked, randomized, prospective trial. METHODS: Thirty-five subjects received
      gatifloxacin in one eye and moxifloxacin in the fellow eye following PRK with a
      9.0-mm epithelial defect. Patients were examined daily after surgery until the
      epithelium had healed completely in both eyes. Beginning on post-operative day 3,
      photos were taken and used to confirm epithelial healing or measure the area of
      residual epithelial defects. Healing times and defect sizes were compared using
      the Wilcoxon signed-ranks test. RESULTS: Both eyes healed on the same day in 18
      of the 35 subjects (51.4%). In 13 of 35 (37.1%) subjects, the moxifloxacin
      treated eye healed first, compared with only four of 35 (11.4%) subjects whose
      gatifloxacin-treated eye healed first. All six of the eyes that took 2 days
      longer than their fellow eye to heal were gatifloxacin-treated. Median healing
      time for both groups was 4 days (moxifloxacin range: 3 to 7 days; gatifloxacin
      range: 3 to 9 days; P = .01), but only 69% of gatifloxacin-treated eyes had
      healed by day 4 compared with 80% of the moxifloxacin-treated eyes. Overall, on
      each post-operative day, defect sizes were greater for the gatifloxacin-treated
      eyes. This difference was statistically significant on day 4 (P = .027).
      CONCLUSIONS: Eyes treated with moxifloxacin healed faster and had smaller defects
      compared with those treated with gatifloxacin. This provides another factor to
      consider in selecting antibiotic prophylaxis for corneal refractive surgery.

PMID- 15953578
TI  - Phlyctenular keratitis associated with meibomitis in young patients.
AB  - PURPOSE: To describe the unique clinical features of phlyctenular keratitis,
      including the association with meibomitis, in young patients. DESIGN:
      Observational case series. METHODS: The study population consisted of 23 Japanese
      patients aged under 35 years with phlyctenular keratitis. We examined their
      clinical history, signs and symptoms, human leukocyte antigen (HLA), bacterial
      cultures of meibum, and the efficacy of antibiotics. The minimal diagnostic
      criteria included corneal nodules consisting of cellular infiltrates and
      superficial neovascularization. RESULTS: Of the 23 patients, 20 (87%) were women,
      and 13 (56.5%) had a history of chalazia. In all cases, the lesions and the
      severity of corneal nodules and neovascularization corresponded well with the
      location and the severity of meibomitis. The frequency of HLA-A26 and HLA-B35 was
      significantly increased in our patients (P = .003 and .016, respectively).
      Propionibacterium acnes in bacterial cultures of pure meibum in 12 of the 20
      patients (60%) was statistically more highly positive than those in four of the
      17 age-matched normal control subjects (23.5%; P = .028). CONCLUSION: The
      characteristics of phlyctenular keratitis in our cases include significantly
      higher prevalence in female patients, severity variation of ocular surface
      manifestation corresponding to meibomitis, specific HLA association, and possible
      P. acnes involvement.

PMID- 15953579
TI  - Disease course of patients with pericentral retinitis pigmentosa.
AB  - PURPOSE: To estimate the mean rates of decline of ocular function in patients
      with an atypical form of retinitis pigmentosa, termed "pericentral retinitis
      pigmentosa." DESIGN: Retrospective observational study. METHODS: setting: Single
      center. patient population: Eighteen patients (ages 32 to 65 years) with
      pericentral retinitis pigmentosa followed for 3 to 26 years. observational
      procedures: Snellen visual acuity, Goldmann visual field area (V-4e white test
      light), and full-field electroretinogram (ERG) amplitudes (0.5 Hz and 30 Hz white
      flashes). main outcome measures: Mean annual exponential rates of change
      quantified by repeated-measures longitudinal regression. RESULTS: Estimated mean
      annual rates of decline of remaining ocular function were 1.2% for visual acuity,
      1.9% for visual field area, 2.5% for ERG amplitude to 0.5 Hz flashes, and 2.9%
      for ERG amplitude to 30 Hz flashes. CONCLUSIONS: The mean rates of loss of
      remaining ocular function of patients with pericentral retinitis pigmentosa were
      generally slower than those previously reported for patients with typical forms
      of retinitis pigmentosa.

PMID- 15953580
TI  - Comparison of protein solubilization methods suitable for proteomic analysis of
      soybean seed proteins.
AB  - Extraction of soybean seed proteins for two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE) and mass spectrometry analysis is challenging and
      inconsistent. In this study, we compared four different protein
      extraction/solubilization methods-urea, thiourea/urea, phenol, and a modified
      trichloroacetic acid (TCA)/acetone-to determine their efficacy in separating
      soybean seed proteins by 2D-PAGE. In all four methods, seed storage proteins were
      well separated by 2D-PAGE with minor variations in the intensity of the spots.
      The thiourea/urea and TCA methods showed higher protein resolution and spot
      intensity of all proteins compared with the other two methods. In addition,
      several less abundant and high molecular weight proteins were clearly resolved
      and strongly detected using the thiourea/urea and TCA methods. Protein spots
      obtained from the TCA method were subjected to mass spectrometry analysis to test
      their quality and compatibility. Fifteen protein spots were selected, digested
      with trypsin, and analyzed using matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography mass
      spectrometry (LC-MS). The proteins identified were beta-conglycinin, glycinin,
      Kunitz trypsin inhibitor, alcohol dehydrogenase, Gly m Bd 28K allergen, and
      sucrose binding proteins. These results suggest that the thiourea/urea and TCA
      methods are efficient and reliable methods for 2D separation of soybean seed
      proteins and subsequent identification by mass spectrometry.

PMID- 15953581
TI  - The five-parameter logistic: a characterization and comparison with the four
      parameter logistic.
AB  - Improvements in assay technology have reduced the amount of random variation in
      measured responses to the point where even slight asymmetry of the assay data can
      be more significant than random variation. Use of the five-parameter logistic
      (5PL) function to fit dose-response data easily accommodates such asymmetry. The
      5PL can dramatically improve the accuracy of asymmetric assays over the use of
      symmetric models such as the four-parameter logistic (4PL) function. Until
      recently, however, the process of fitting the 5PL function has been difficult,
      with the result that the 4PL function has continued to be used even for highly
      asymmetric data. Various ad hoc modifications of the 4PL method have been
      developed in an attempt to address asymmetric data. However, recent advances in
      numerical methods and assay analysis software have rendered easier the fitting of
      the 5PL routine. This paper demonstrates how use of the 5PL function can improve
      assay performance over the 4PL and its variants. Specifically, the improvement in
      the accuracy of concentration estimates that can be obtained using the 5PL over
      the 4PL as a function of the asymmetry present in the data is studied. The
      behavior of the 5PL curve and how it differs from the 4PL curve are discussed.
      Common experimental designs, which can lead to ill-conditioned regression
      problems, are also examined.

PMID- 15953582
TI  - 2,3,7,8-tetrachlorodibenzo-p-dioxin induces CYP1B1 expression in human luteinized
      granulosa cells.
AB  - The environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a
      reproductive toxicant in multiple species; however, mechanisms and direct ovarian
      effects are poorly understood. DNA microarrays were used to characterize gene
      expression profiles of human luteinized granulosa cells (HLGCs) exposed to TCDD
      in primary cultures. Exposure to 10 nM TCDD for 24 h induced a significant
      increase in CYP1B1, while few other genes responded. TaqMan PCR and Western
      immunoblotting demonstrated that induction was dose-dependent. Additionally, the
      microsomal form of catechol-O-methyltransferase (COMT) was highly expressed in
      HLGCs, along with only fractional amounts of the soluble form. This is the first
      report of CYP1B1 and COMT expression, and CYP1B1 induction, in cells from the
      human ovary. The role of CYP1B1 in the oxidative metabolism of estrogens and
      potential generation of DNA adducts in the ovary may have significant
      consequences for oocyte quality, corpus luteum function, and ovarian
      carcinogenesis.

PMID- 15953583
TI  - Oligomerization of H(+)-pyrophosphatase and its structural and functional
      consequences.
AB  - The H(+)-pyrophosphatase (H(+)-PPase) consists of a single polypeptide,
      containing 16 or 17 transmembrane domains. To determine the higher order
      oligomeric state of Streptomyces coelicolor H(+)-PPase, we constructed a series
      of cysteine substitution mutants and expressed them in Escherichia coli. Firstly,
      we analyzed the formation of disulfide bonds, promoted by copper, in mutants with
      single cysteine substitutions. 28 of 39 mutants formed disulfide bonds, including
      S545C, a substitution at the periplasmic side. The formation of intermolecular
      disulfide bonds suppressed the enzyme activity of several, where the substituted
      residues were located in the cytosol. Creating disulfide links in the cytosol may
      interfere with the enzyme's catalytic function. Secondly, we prepared double
      mutants by introducing second cysteine substitutions into the S545C mutant. These
      double-cysteine mutants produced cross-linked complexes, estimated to be at least
      tetramers and possibly hexamers. Thirdly, we co-expressed epitope-tagged, wild
      type, and inactive mutant H(+)-PPases in E. coli and confirmed the formation of
      oligomers by co-purifying one subunit using the epitope tag used to label the
      other. The enzyme activity of these oligomers was markedly suppressed. We propose
      that H(+)-PPase is present as an oligomer made up of at least two or three sets
      of dimers.

PMID- 15953584
TI  - Schema modes and childhood abuse in borderline and antisocial personality
      disorders.
AB  - Complex personality disorders (PDs) have been hypothesized to be characterized by
      alternating states of thinking, feeling and behavior, the so-called schema modes
      (Young, Klosko, & Weishaar (2003). Schema therapy: A practioner's guide. New
      York: Guilford). The present study tested the applicability of this model to
      borderline personality disorders (BPD) and antisocial personality disorders
      (APD), and related it to a presumed common etiological factor, childhood trauma.
      Sixteen patients with BPD, 16 patients with APD and 16 nonpatient controls (all
      50% of both sexes) completed a Schema Mode Questionnaire assessing cognitions,
      feelings and behaviors characteristic of six schema modes. Participants were
      interviewed to retrace abusive sexual, physical and emotional events before the
      age of 18. BPD as well as APD participants were characterized by four maladaptive
      modes (Detached Protector, Punitive Parent, Abandoned/Abused Child and Angry
      Child). APD displayed most characteristics of the Bully/Attack mode, though not
      significantly different from BPD. The Healthy Adult mode was of low presence in
      BPD and of high presence in APD and the nonpatients. Frequency and severity of
      the three kinds of abuse were equally high in both PD groups, and significantly
      higher than in nonpatients.

PMID- 15953585
TI  - Application of ES cells for generation of respiration-deficient mice carrying
      mtDNA with a large-scale deletion.
AB  - In a previous study, we used mouse zygotes as recipients of mtDNA with a large
      scale deletion mutation (DeltamtDNA) and generated respiration-deficient mice
      (mito-mice) carrying DeltamtDNA. In this study, we used mouse ES cells as
      recipients of DeltamtDNA, and generated mito-mice with DeltamtDNA only when the
      ES cells carried 17% DeltamtDNA. No chimera mice or their F(1) progenies were
      obtained from ES cells carrying more than 61% DeltamtDNA. These observations
      suggest that respiratory defects of ES cells inhibit their normal differentiation
      into chimera mice and mito-mice, and that ES cells are more effective than
      zygotes for generation of mito-mice carrying mtDNAs without significant
      pathogenic mutations.

PMID- 15953586
TI  - Exogenous administration of octanoic acid accelerates octanoylated ghrelin
      production in the proventriculus of neonatal chicks.
AB  - Ghrelin is modified by fatty acid at the third serine residue. In this study,
      derivation of fatty acid for acylation of ghrelin was investigated using a
      hatchling chicken model. We first studied ghrelin gene expression and production
      in the neonatal chick proventriculus and then investigated the effect of
      exogenous octanoic acid (OA) administration on acylated ghrelin production. In a
      free-feeding condition on day 2.5 after hatching, the density of ghrelin mRNA
      expressing (ghrelin-ex) cells was greater than that of ghrelin-immunopositive
      (ghrelin-ip) cells, but no difference was found between those densities in adult
      chickens. Intraperitoneal or oral administration of OA for a few days
      significantly increased the density of ghrelin-ip cells without any changes in
      ghrelin-ex cells and elevated only octanoylated ghrelin levels in the
      proventriculus. The results indicate that fatty acid absorbed from food is
      directly utilized in acylated ghrelin production in the chicken.

PMID- 15953587
TI  - Apoptosis signal-regulating kinase 1 is involved not only in apoptosis but also
      in non-apoptotic cardiomyocyte death.
AB  - The molecular basis of myocardial cell death in the ischemia-reperfused heart
      still remains to be clarified. Apoptosis signal-regulating kinase 1 (ASK1) is a
      mitogen-activated protein kinase kinase kinase that plays an important role in
      stress-induced apoptosis. We studied ASK1(-/-) mice to examine the role of ASK1
      in ischemia-reperfusion injury. In the wild-type heart, ischemia-reperfusion
      resulted in necrotic injury, whereas infarct size was drastically reduced in the
      ASK1(-/-) heart. The necrotic injury was not accompanied with any evidence of
      apoptosis such as an increase in TUNEL-positive cells, DNA fragmentation or the
      activation of caspase-3. ASK1(-/-) cardiomyocytes were more resistant to H(2)O(2)
      or Ca(2+)-induced apoptotic and non-apoptotic cell death compared with wild-type
      cells. These data suggest that ASK1 is involved in necrosis as well as apoptosis
      and that ASK1-dependent necrosis is likely to contribute to myocardial cell death
      in the ischemia-reperfused heart.

PMID- 15953588
TI  - Angiogenesis inhibitors: from laboratory to clinical application.

PMID- 15953589
TI  - The impact of reward, punishment, and frustration on attention in pediatric
      bipolar disorder.
AB  - BACKGROUND: Theories in affective neuroscience suggest that mood disorders
      involve perturbations in attention-emotion interactions. We tested the hypothesis
      that frustration adversely impacts attention and behavior in children with
      bipolar disorder (BPD). METHODS: Thirty-five children with BPD and 26 normal
      control subjects completed: 1) a Posner attention task with feedback but no
      contingencies; 2) an affective Posner with contingencies; and 3) an affective
      Posner that used rigged feedback to induce frustration. Reaction time (RT) and
      event-related potential (ERP) data were collected. RESULTS: At baseline (task 1),
      there were no between-group differences in behavior or ERPs. Children with BPD
      exhibited reduced parietal P3 amplitude on task 3 only. On trials occurring after
      negative feedback, control subjects showed decreased RT when contingencies were
      introduced (task 2), whereas BPD subjects did not. CONCLUSIONS: The introduction
      of contingencies was associated with impaired performance of children with BPD,
      suggesting deficits in their ability to adapt to changing contingencies. In
      addition, frustration was associated with disrupted attention allocation in
      children with BPD. We hypothesize that children with BPD inappropriately deployed
      attention to their internal frustration rather than to the task, causing impaired
      performance.

PMID- 15953591
TI  - Brain serotonin depletion by lesions of the median raphe nucleus enhances the
      psychotomimetic action of phencyclidine, but not dizocilpine (MK-801), in rats.
AB  - We have previously shown that brain serotonin depletion by lesions of the median
      raphe nucleus (MRN) causes enhancement of phencyclidine-induced locomotor
      hyperactivity [S. Kusljic, D.L. Copolov, M. van den Buuse, Differential role of
      serotonergic projections arising from the dorsal and median raphe nuclei in
      locomotor hyperactivity and prepulse inhibition, Neuropsychopharmacology 28
      (2003) 2138-2147]. In this study, we extend our previous work by (1) comparing
      the effect of phencyclidine with that of another NMDA receptor antagonist,
      dizocilpine (MK-801); (2) investigate behavioral changes in more detail; (3)
      assess in detail the effect of raphe lesions on regional serotonin levels in the
      brain. Male Sprague-Dawley rats received microinjection of the serotonergic
      neurotoxin 5,7-dihydroxytryptamine into the MRN or dorsal raphe nucleus (DRN).
      The effects of treatment with saline, phencyclidine and MK-801 on locomotor
      activity were determined 2 weeks after the surgery. MRN lesions caused serotonin
      depletion in the dorsal hippocampus, whereas DRN lesions caused serotonin
      depletion in the frontal cortex, striatum and ventral hippocampus. There was a
      significant increase in phencyclidine-induced locomotor hyperactivity in the MRN
      lesioned group compared to sham-operated controls. Further analysis of behavior
      showed that phencyclidine-induced hyperambulation, but not stereotypy or rearing,
      was significantly higher in MRN-lesioned rats compared to controls. In contrast,
      there was no significant effect of the lesions on the psychotomimetic effect of
      MK-801. These results indicate that a hyposerotonergic state induced by
      destruction of projections from the MRN leads to altered brain circuitry that is
      responsible for the regulation of phencyclidine-but not MK-801-induced locomotor
      hyperactivity. Thus, MRN projections may play an inhibitory role in mechanisms
      involved in symptoms of schizophrenia.

PMID- 15953590
TI  - Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of
      elderly depressed patients.
AB  - BACKGROUND: Elderly depressed patients have more vascular hyperintensities in
      frontal white matter and basal ganglia than elderly control subjects. Cell
      pathology that might be related to increased vascular hyperintensities has not
      been examined. METHODS: Postmortem samples from the orbitofrontal cortex (ORB)
      were collected in 15 elderly subjects with major depressive disorder (MDD) and 11
      age-matched control subjects. Cell packing density of neurons and glia, density
      of pyramidal and nonpyramidal neurons, and cortical and laminar width were
      measured. RESULTS: The overall (layers I-VI) packing density of ORB neurons with
      pyramidal morphology was markedly decreased in MDD (by 30%) as compared with
      control subjects. Further laminar analysis of pyramidal neurons density revealed
      significant reductions in layers IIIc and V in MDD. In contrast, in MDD the
      density of nonpyramidal neurons and glia and cortical and laminar width were
      comparable to control values. CONCLUSIONS: In elderly subjects with depression,
      the density of pyramidal neurons in the ORB was particularly low in cortical
      layers V and III, the origin of prefronto-striatal and prefronto-cortical and
      prefronto-amygdalar projections. Degeneration of neurons furnishing these
      projections might be related to the white matter hyperintensities previously
      observed. Neuronal pathology seems to be more severe in elderly than in younger
      subjects with MDD.

PMID- 15953592
TI  - The anti-inflammatory effect of peripheral bee venom stimulation is mediated by
      central muscarinic type 2 receptors and activation of sympathetic preganglionic
      neurons.
AB  - The anti-inflammatory effect (AI) induced by peripheral injection of diluted bee
      venom (dBV) involves activation of spinal cord circuits and is mediated by
      catecholamine release from adrenal medulla, but the precise neuronal mechanisms
      involved are not fully understood. In a recent study, we demonstrated that an
      increase in spinal acetylcholine is involved in mediating the anti-inflammatory
      effect of dBV and that this mediation also involves adrenomedullary activation.
      The present study utilized the mouse air pouch inflammation model to evaluate the
      involvement of spinal acetylcholine receptors and sympathetic preganglionic
      neurons (SPNs) in dBV's anti-inflammatory effect (dBVAI). Intrathecal (IT)
      pretreatment with atropine (muscarinic cholinergic antagonist) but not
      hexamethonium (nicotinic cholinergic antagonist) significantly suppressed dBVAI
      on zymosan-evoked leukocyte migration. Subsequent experiments showed that IT
      pretreatment with methoctramine (a muscarinic receptor type 2; M(2) antagonist),
      but not pirenzepine (an M(1) antagonist) or 4-DAMP (an M(3) antagonist),
      suppressed the dBVAI. In addition, dBV stimulation specifically increased Fos
      expression in SPNs of the T7-T11, but not the T1-T6 or T12-L2 spinal cord
      segments, in animals with zymosan-induced inflammation. Moreover, IT
      methoctramine pretreatment suppressed this dBV-induced Fos expression
      specifically in SPNs of T7-T11 level. Peripheral sympathetic denervation using 6
      hydroxydopamine (6-OHDA) treatment (which spares sympathetic adrenal medullary
      innervation) did not alter dBVAI. Collectively these results indicate that dBV
      stimulation leads to spinal cord acetylcholine release that in turn acts on
      spinal M(2) receptors, which via a hypothesized disinhibition mechanism activates
      SPNs that project to the adrenal medulla. This activation ultimately leads to the
      release of adrenal catecholamines that contribute to dBVAI.

PMID- 15953593
TI  - Synthesis of poly-O-sulfated glycosides of 2,5-anhydro-D-mannitol.
AB  - 2,5-Anhydro-3-O-beta-D-glucopyranosyl-; -3-O-alpha-L-idopyranosyl-; -3-O-alpha-D
      arabinopyranosyl-; -3-O-alpha-L-arabinopyranosyl-; -3-O-beta-D-maltopyranosyl-; 
      3-O-beta-D-gentiobiopyranosyl-; -1,6-di-O-beta-D-glucopyranosyl-; -1,6-di-O-alpha
      L-idopyranosyl-; -1-O-beta-D-maltopyranosyl-; -1,3,6-tri-O-beta-D-glucopyranosyl
      ; -1,6-di-O-beta-maltopyranosyl- and -1,6-di-O-beta-D-gentiobiopyranosyl-2,5
      anhydro-D-mannitol as well as their poly-O-sulfated derivatives were synthesized.
      The IP3-IC50 values of their sodium and/or potassium salts were determined for
      structure-activity studies aiming at the synthesis of new, orally active
      antiasthmatic compounds.

PMID- 15953594
TI  - Membrane association of nitric oxide-sensitive guanylyl cyclase in
      cardiomyocytes.
AB  - OBJECTIVE: Although the importance of the cyclic GMP (cGMP) signaling pathway in
      cardiac myocytes is well established, little is known about its regulation. Ca2+
      dependent translocation of nitric oxide (NO) sensitive guanylyl cyclase (GCNO) to
      the cell membrane has been recently proposed to play a role. The aim of this
      study was to determine the possible functional relevance of GCNO bound to the
      cardiomyocyte membrane. METHODS: Cytosolic and particulate fractions of adult rat
      cardiomyocytes were isolated and blotted, and their GCNO activity was assayed in
      parallel experiments. RESULTS: In untreated cardiomyocytes, approximately 30% of
      beta1-and alpha1-subunits of GCNO and a similar proportion of GCNO activity were
      found in the particulate fraction. The dependence of GCNO activity on pH, Ca2+,
      GTP and NO donor concentrations was similar in particulate and cytosolic
      fractions. Treatment of cardiomyocytes with the ionophore A23187 caused GCNO to
      translocate to the sarcolemma, increased GCNO activity in this fraction, and
      potentiated NO-mediated cGMP synthesis. These effects appeared to be mediated by
      Ca2+-dependent changes on the phosphorylation status of GCNO, since they were
      enhanced by the non-selective inhibitor staurosporine and by the selective
      inhibitor of Ca2+/calmodulin-dependent protein kinase KN-93. The effect of drugs
      increasing intracellular Ca2+ on cGMP synthesis was clearly correlated with their
      effects on membrane-associated GCNO activity but not with their effects on
      cytosol-associated GCNO. CONCLUSION: These results are the first evidence that 1)
      GCNO is associated with the cell membrane in cardiomyocytes, 2) the regulation of
      membrane-associated GCNO differs from that of cytosolic GCNO, and 3) membrane
      association may have a crucial role in determining the response of cells to NO.

PMID- 15953595
TI  - Functional evidence that in the cardiovascular system AT1 angiotensin II
      receptors are AT1B prejunctionally and AT1A postjunctionally.
AB  - Numerous studies have shown that angiotensin II causes vasoconstriction both by a
      direct action on smooth muscle cells (postjunctional effect) and indirectly
      through the facilitation of noradrenaline release from postganglionic sympathetic
      neurons (prejunctional effect). The receptors through which angiotensin II exerts
      its actions were first divided into AT1 and AT2 subtypes. A further subdivision
      of AT1 receptors into AT1A and AT1B subtypes was based on cloning and receptor
      binding studies: AT1A showed a high affinity for losartan, but low affinity for
      PD123319, while AT1B receptors showed nearly 100-fold lower affinity for losartan
      and 10,000-fold higher affinity for PD123319 relative to AT1 sites. The present
      review deals with functional evidence supporting the existence of AT1A and AT1B
      subtypes in the cardiovascular system. Taken together, all the functional results
      obtained in vivo and in vitro-in a wide variety of vascular tissues from
      different species-allow one to conclude that angiotensin II AT1 receptors are
      different pre- and postjunctionally and also that prejunctional and
      postjunctional angiotensin II receptors most probably belong to AT1B and AT1A
      subtypes, respectively.

PMID- 15953596
TI  - Does the polymorphism of MHC class II promoters matter?
AB  - The promoters of genes of the major histocompatibility complex vary not only
      because of linkage disequilibrium with their coding sequences but also, we argue,
      because of natural selection that acts particularly strongly on MHC II gene
      promoters. Thus, the promoter of H2Eb varies more than that of H2K, to an extent
      that cannot be accounted for by coding variation, and the same applies to
      HLA.DRB1 in comparison with H2D. We discuss how transduction by lentivirus
      vectors followed by adoptive transfer of monoclonal T cells could be used to test
      the functional activity of variant mouse promoters in vivo, and how homologous
      recombination in suitable cell lines might provide a short cut to obtaining
      promoter knock-ins.

PMID- 15953597
TI  - Fluorescence is less sensitive than ultraviolet or electrochemical detection for
      measurement of coenzyme Q10 in plasma.

PMID- 15953598
TI  - Persistency of high proinflammatory cytokine levels from colostrum to mature milk
      in preeclampsia.
AB  - OBJECTIVES: Recent evidence suggests a role of an excessive maternal inflammatory
      response in the pathogenesis of preeclampsia. Whether this imbalance can be
      transferred from mother to breast milk remains to be established. DESIGN AND
      METHODS: 15 preeclamptic and 15 healthy pregnant women were recruited in this
      study. Colostrum and milk samples were collected postpartum in the first 48 h and
      at 30 days, respectively. Samples were analyzed for interleukin (IL)-1beta, IL-6,
      IL-8, tumor necrosis factor (TNF)-alpha and soluble IL-2R (sIL-2R) levels with
      chemiluminescence enzyme immunometric assays. RESULTS: Colostrum cytokine levels
      corrected for gestational age and type of delivery were not significantly
      different in the two groups. Cytokine levels significantly decreased in mature
      milk versus colostrum in the control group (P < 0.05), but did not significantly
      decrease in the preeclampsia group (P > 0.05), except for TNF-alpha (P < 0.05).
      Mature milk IL-8 and TNF-alpha levels were higher in the preeclampsia group
      versus controls (P < 0.05). CONCLUSION: Results of this study show that
      proinflammatory cytokines in breast milk exhibit biological variation at
      different periods of human lactation. In preeclampsia, high cytokine levels
      persist at least for 30 days. These results suggest that preeclampsia may affect
      milk cytokine balance and offer an immunological signal for the host defense in
      high-risk neonates.

PMID- 15953599
TI  - Sweat collection for testing in Canadian Cystic Fibrosis Centers, is it optimal?
AB  - OBJECTIVES: The goal of this study was to examine the ability of the current
      Canadian CF center network to conduct sweat testing, with a particular focus on
      testing in infants less than 3 months old. METHODS: Surveys were sent to the 37
      CF centers in Canada supported by the Canadian CF Foundation, and results were
      interpreted with respect to their ability to obtain adequate sweat volumes in
      children less than 3 months and potential factors influencing these results.
      RESULTS: Ten centers that care for adult patients referred patients to their
      local pediatric CF center for sweat testing; the remaining 27 centers conducted
      sweat tests and 26 responded. Insufficient sweat volume results in children <3
      months occurred in a median of 18.3% of tests. The corresponding proportion for
      the remaining population was 4.5% (P < 0.001). 15 of 19 centers had an incidence
      of >5% of insufficient tests in children <3 months of age, and 9 of 19 had an
      incidence of <20% in this age group. Six of 19 had an incidence of >5% of
      insufficient sweat volumes in older children and adults. CONCLUSIONS:
      Standardization of testing procedures is required to reduce the rates of
      insufficient sweat volumes in both infants less than 3 months old and children >3
      months old. This will decrease the need for repeat testing and delay in
      diagnosis.

PMID- 15953600
TI  - Ankyrin-G in skeletal muscle: tissue-specific alternative splicing contributes to
      the complexity of the sarcolemmal cytoskeleton.
AB  - Ankyrins are versatile adaptor proteins that join the spectrin-based cytoskeleton
      to transmembrane proteins, and have roles in organizing the microstructure of
      cell membranes. Molecular diversity of ankyrins in mammals arises from extensive
      alternative splicing of the products of three genes. There has been no systematic
      analysis of the diversity of expression of ankyrins-G, the widely expressed Ank3
      gene products, in a complex tissue. We previously described Ank(G107), the first
      muscle-specific ankyrin-G. Here, we combined cDNA and database analyses to gain
      novel insight into the ankyrins-G of skeletal muscle. We find: (i) that Ank3 is
      composed of at least 53 exons, many of which are subject to tissue-specific
      splicing; (ii) five novel full-length cDNAs encoding two canonical (Ank(G197),
      Ank(G217)) and three small isoforms (Ank(G109), Ank(G128), Ank(G130)) bring to
      six the number of ankyrins-G expressed in skeletal muscle; (iii) a 76-residue
      insert in the C-terminal domain is a 'signature' for muscle ankyrins; (iv)
      variably spliced sequences of 17/18 and 195 residues increase diversity in the C
      terminal domains. Comparison of endogenous ankyrins-G with in vitro translated
      cDNAs revealed that small ankyrins account for the majority of the
      immunoreactivity for ankyrin-G in soleus muscle. The small ankyrins, when
      expressed in vivo in the rat muscle, are all targeted to sarcolemmal costameres.
      Our results demonstrate the tissue-dependent alternative splicing of Ank3 in
      skeletal muscle and point to novel functions of small ankyrins-G in organizing
      microdomains of the plasma membrane.

PMID- 15953601
TI  - Erythropoietin receptor Y479 couples to ERK1/2 activation via recruitment of
      phospholipase Cgamma.
AB  - Red blood cell development is primarily controlled by erythropoietin (EPO).
      Several studies have revealed the importance of EPO-R Y343 and Y479 for erythroid
      cell growth, differentiation, and survival. In order to isolate critical
      signaling proteins that bind to EPO-R, we initiated a Cloning of Ligand Target
      (COLT) screen using a murine embryonic day 16 phage library and a biotinylated
      EPO-R Y343 phosphopeptide. One of the clones isolated encodes Phospholipase C
      (PLC)gamma1. PLCgamma1 is rapidly tyrosine phosphorylated upon EPO stimulation
      and associates with EPO-R in an SH2-domain-dependent manner. Although PLCgamma1
      bound EPO-R Y343, Y401, Y429, Y431, and Y479 in the COLT screen, PLCgamma1
      required Y479 for association with EPO-R in Ba/F3-EPO-R cells. Studies have
      identified EPO-R Y479 as important for ERK activation. Since PI3-kinase binds EPO
      R Y479, one group has suggested that ERK activation downstream of PI3-kinase
      accounts for the importance of this residue in EPO signaling. However, we show
      that inhibition of PI3-kinase does not abolish ERK activation. Furthermore, we
      demonstrate interaction of PLCgamma1 with Grb2 and SOS2. Hence, we have
      identified a novel adapter function for PLCgamma1 in EPO signaling in which
      recruitment of PLCgamma1 to EPO-R may lead to activation of the ERK pathway.

PMID- 15953603
TI  - Impaired nuclear translocation of CAR in hepatic preneoplastic lesions:
      association with an attenuated CYP2B induction by phenobarbital.
AB  - Phenobarbital (PB) induction of CYP2B, a representative target gene of
      constitutive androstane receptor (CAR), has been observed to be attenuated in
      preneoplastic lesions of rat liver; however, molecular basis for this attenuation
      is poorly understood. In this report, we provide evidence indicating that the CAR
      expressed in the hepatic preneoplastic lesions of rats and mice was resistant to
      nuclear translocation and transactivation of the PB-responsive enhancer module
      upon PB treatment. These observations suggest that the attenuation of the
      induction of CYP2B by PB in hepatic preneoplastic lesions is evidently a
      consequence of impaired nuclear translocation of CAR.

PMID- 15953602
TI  - Myelin-associated glycoprotein and complementary axonal ligands, gangliosides,
      mediate axon stability in the CNS and PNS: neuropathology and behavioral deficits
      in single- and double-null mice.
AB  - Complementary interacting molecules on myelin and axons are required for long
      term axon-myelin stability. Their disruption results in axon degeneration,
      contributing to the pathogenesis of demyelinating diseases. Myelin-associated
      glycoprotein (MAG), a minor constituent of central and peripheral nervous system
      myelin, is a member of the Siglec family of sialic acid-binding lectins and binds
      to gangliosides GD1a and GT1b, prominent molecules on the axon surface. Mice
      lacking the ganglioside biosynthetic gene Galgt1 fail to express complex
      gangliosides, including GD1a and GT1b. In the current studies, CNS and PNS
      histopathology and behavior of Mag-null, Galgt1-null, and double-null mice were
      compared on the same mouse strain background. When back-crossed to >99% C57BL/6
      strain purity, Mag-null mice demonstrated marked CNS, as well as PNS, axon
      degeneration, in contrast to prior findings using mice of mixed strain
      background. On the same background, Mag- and Galgt1-null mice exhibited
      quantitatively and qualitatively similar CNS and PNS axon degeneration and nearly
      identical decreases in axon diameter and neurofilament spacing. Double-null mice
      had qualitatively similar changes. Consistent with these findings, Mag- and
      Galgt1-null mice had similar motor behavioral deficits, with double-null mice
      only modestly more impaired. Despite their motor deficits, Mag- and Galgt1-null
      mice demonstrated hyperactivity, with spontaneous locomotor activity
      significantly above that of wild type mice. These data demonstrate that MAG and
      complex gangliosides contribute to axon stability in both the CNS and PNS.
      Similar neuropathological and behavioral deficits in Galgt1-, Mag-, and double
      null mice support the hypothesis that MAG binding to gangliosides contributes to
      long-term axon-myelin stability.

PMID- 15953604
TI  - Sp1 elements in SULT2B1b promoter and 5'-untranslated region of mRNA: Sp1/Sp2
      induction and augmentation by histone deacetylase inhibition.
AB  - The steroid/sterol sulfotransferase gene (SULT2B1) encodes for two isozymes of
      which one (SULT2B1b) sulfonates cholesterol and is selectively expressed in skin.
      The human SULT2B1 gene contains neither a TATAAA nor a CCAAT motif upstream of
      the coding region for SULT2B1b; however, this area is GC-rich. Of five Sp1
      elements identified two had regulatory activity utilizing immortalized human
      keratinocytes: one element is located above the ostensible transcription
      initiation site, whereas the other is located within the 5'-untranslated region
      of the SULT2B1b mRNA. Sp1 and Sp2 transcription factors identified by supershift
      analyses induced reporter gene activity, an effect markedly augmented by histone
      deacetylase inhibition.

PMID- 15953605
TI  - Adipose tissues as an ancestral immune organ: site-specific change in obesity.
AB  - Close relationships have been demonstrated between adipose tissue and the
      inflammatory/immune system. Furthermore, obesity is increasingly considered as a
      state of chronic inflammation. Cytofluorometric analysis reveals the presence of
      significant levels of lymphocytes in the stroma-vascular fraction of white
      adipose tissues. In epididymal (EPI) fat, lymphocytes display an "ancestral"
      immune system phenotype (up to 70% of natural killer (NK), gammadelta+ T and NKT
      cells among all lymphocytes) whereas the inguinal (ING) immune system presents
      more adaptive characteristics (high levels of alphabeta+ T and B cells). The
      percentage of NK cells in EPI fat was decreased in obese mice fed with a high-fat
      diet, whereas gammadelta positive cells were significantly increased in ING fat.
      These data support the notion that adipose tissue may elaborate immunological
      mechanisms to regulate its functions which might be altered in obesity.

PMID- 15953606
TI  - Mechanical stimulation effects on functional end effectors in osteoblastic MG-63
      cells.
AB  - Receptor activator of Nf-kappaB ligand (RANKL) and osteoprotegerin (OPG) have
      been implicated in bone metabolism. Specifically, the balance of these factors in
      conjunction with receptor activator of Nf-kappaB (RANK) is believed to be key in
      determining the rate of osteoclastogenesis and the net outcome of bone
      formation/resorption. While it is well accepted that mechanical loading in vivo
      affects bone formation/resorption and that alterations in the responsiveness of
      bone cells to mechanical loading have been implicated in metabolic bone diseases,
      the effect of in vitro mechanical loading on osteoblastic production of OPG and
      RANKL has not been extensively studied. Thus, in the current study, we developed
      an in vitro model to load human osteoblasts and studied levels of OPG, RANKL,
      PGE(2) and macrophage colony stimulating factor (M-CSF). We hypothesized that
      stimulating osteoblastic cells would increase the release of soluble OPG relative
      to RANKL favoring a bone-forming (and resorption-inhibiting) event. To accomplish
      this, we developed a small-scale loading machine that imparts via bending, well
      defined substrate deformation to bone cells cultured on artificial substrates.
      Following 2h of loading and a 1h incubation period, media was collected and
      levels of soluble OPG, RANKL, PGE(2) and M-CSF were quantified using ELISA and
      western blotting. We found that mechanical loading significantly increased
      soluble OPG levels relative to RANKL at this 3h time point. Levels of soluble and
      cellular RANKL detected were not significantly affected by mechanical
      stimulation. The relative shift in abundance of OPG over RANKL associated with
      applied mechanical stimulation suggests the soluble OPG:RANKL ratio may be
      important in load-induced coupling mechanisms of bone cells.

PMID- 15953607
TI  - 3D models of blood flow in the cerebral vasculature.
AB  - The circle of Willis (CoW) is a ring-like arterial structure located in the base
      of the brain and is responsible for the distribution of oxygenated blood
      throughout the cerebral mass. To investigate the effects of the complex 3D
      geometry and anatomical variability of the CoW on the cerebral hemodynamics, a
      technique for generating physiologically accurate models of the CoW has been
      created using a combination of magnetic resonance data and computer-aided design
      software. A mathematical model of the body's cerebral autoregulation mechanism
      has been developed and numerous computational fluid dynamics simulations
      performed to model the hemodynamics in response to changes in afferent blood
      pressure. Three pathological conditions were explored, namely a complete CoW, a
      fetal P1 and a missing A1. The methodology of the cerebral hemodynamic modelling
      is proposed with the potential for future clinical application in mind, as a
      diagnostic tool.

PMID- 15953608
TI  - Macroporous ZrO2 ceramics prepared from colloidally stable nanoparticles building
      blocks and organic templates.
AB  - ZrO2 macroporous materials with well-ordered structures were prepared using nano
      ZrO2 particles as the building materials and polystyrene spheres as the organic
      templates. A well-dispersed nano-ZrO2 suspension with a narrow particle size
      distribution was prepared by deagglomeration of as-received nano-ZrO2 powders via
      ultrasonication, and then centrifugation was performed to remove agglomerated
      bigger particles. Negatively charged polystyrene spheres were uniformly coated
      with positively charged nano-ZrO2 particles by means of electrostatic attraction
      at pH 4. Green samples were prepared by slip casting from colloidally stable
      suspension of nano-ZrO2 coated polystyrene spheres. ZrO2 macroporous materials
      with well-ordered microstructure derived from the nano-ZrO2 coated polystyrene
      spheres.

PMID- 15953609
TI  - An elastic-plastic hybrid adhesion model for contacting rough surfaces in the
      presence of molecularly thin lubricant.
AB  - The study of adhesion has received considerable attention in recent years, partly
      due to advances in the design and fabrication of micro/nano devices. Many
      adhesion investigations are centered on single-spherical-contact models, which
      include the classic Johnson-Kendall-Roberts (JKR), improved Derjaguin-Muller
      Toporov (IDMT), and Maugis-Dugdale (MD) models. Based on the IDMT single-asperity
      model, adhesive rough surface contact models have also been developed, which are
      valid for elastic and elastic-plastic contact conditions. A limitation of the
      IDMT-based models is that they are only valid for application cases with low
      adhesion parameter values. In this research, a contacting rough surface adhesion
      model was developed by combining an extended Maugis-Dugdale (EMD) model (which is
      only valid for elastic contacts) with an IDMT-based elastic-plastic adhesion
      model. The proposed model, termed the elastic-plastic hybrid adhesion model, is
      valid for the entire adhesion parameter range and also for elastic-plastic
      contacts. The proposed model gives results similar to the EMD rough surface model
      when the contact is primarily elastic. Moreover, the proposed model was compared
      to an IDMT-based model (ISBL model) and both gave similar results for contacts
      with low adhesion parameter values. With high adhesion parameter values, the ISBL
      model fails, whereas the proposed model correctly predicts higher adhesion. Last,
      based on the stiffness of the external force, the instability for adhesive rough
      surfaces in contact was also discussed, and it was postulated that a high peak
      value of the external force stiffness directly relates to the unstable contact
      process.

PMID- 15953610
TI  - Knowledge-based reconstruction of random porous media.
AB  - An evolutionary optimization technique is used to reconstruct digitized material
      models of 300(3) nm3 size for mesoporous two-phase systems. The models are
      adapted to the two-point probability (TPP) and to a volume-based pore-size
      distribution (PSD) which were derived from SANS and adsorption experiments and
      which carry statistical information about morphology and topology of the pore
      system. To avoid extreme update-costs, the bulk of mutations are assessed by
      means of a suitable approximation of the PSD; it is demonstrated that a sporadic
      insertion of the PSD suffices to drive the algorithm towards satisfactory models
      in acceptable time. Our approach is knowledge-based in the sense that (i) the
      mutations are restricted to expedient exchanges of phase-voxels by a heuristic
      rule, and (ii) the sporadic calculation of the PSD from the current state of the
      model, in essence, provides an efficient self-control for the evolutionary
      process. We applied the method to reconstruct periodic models of the xerogel
      Gelsil 200. Such reconstructs of real mesoporous solids could be utilized, for
      instance, to verify theories of adsorption and capillary condensation.

PMID- 15953611
TI  - Oxidation process induced by 2-mercaptopyrimidine at a mercury electrode.
AB  - The oxidation process induced by 2-mercaptopyrimidine (RSH) at a hanging mercury
      drop electrode was studied in aqueous media by normal and cyclic voltammetry. The
      results indicate the formation of a weakly adsorbed HgSR complex according to the
      reaction Hg+RSH-->HgSR+e(-)+H+. When the surface excess of HgSR is high, a two
      dimensional condensation takes place if the potential is positive enough, as
      proved by phase-sensitive ac and cyclic voltammetry.

PMID- 15953612
TI  - Rapid adsorption and entrapment of benzoic acid molecules onto mesoporous silica
      (FSM-16).
AB  - Changes in the molecular state of benzoic acid (BA) in the presence of folded
      sheet mesoporous material (FSM-16), which has uniformly sized cylindrical
      mesopores and a large surface area, were assessed with several analyses. When BA
      was blended with FSM-16 for 5 min (BA content=30%), the X-ray diffraction peaks
      of BA crystals disappeared, suggesting an amorphous state. Fluorescence analysis
      of the mixture showed a new fluorescence emission peak for BA at 386 nm after
      mixing with FSM-16. Fluorescence lifetime analysis of the BA component in the
      mixture at 386 nm showed a longer lifetime in comparison with that of BA
      crystals. The solid-state (13)C CP/MAS and PST/MAS NMR spectra of the mixture
      with FSM-16 showed a significantly different spectral pattern from the mixture
      with nonporous glass, whose NMR spectra were identical to those of BA crystals.
      These results indicate that BA molecules disperse quickly into the hexagonal
      channels of FSM-16 by a simple blending procedure and adsorbed BA molecules had
      clearly different physicochemical properties to BA crystals.

PMID- 15953613
TI  - Nonlinear stability analysis of a two-layer thin liquid film: dewetting and
      autophobic behavior.
AB  - The nonlinear stability analysis of a liquid film composed of two superposed thin
      layers of immiscible liquids resting on a solid substrate is performed. It is
      shown that the coupling of van der Waals interactions in the two layers can lead
      to an autophobic behavior in the form of spinodal decomposition of two planar
      liquid layers into a system of localized drops divided by almost planar wetting
      layers. The results of the weakly nonlinear analysis near the instability
      threshold are confirmed by the numerical solution of a system of two strongly
      nonlinear evolution equations for the liquid-liquid and liquid-gas interfaces.
      The kinetics of the drop coarsening at late stages is studied and is found to be
      close to that reported for a one-layer film. It is also shown that gravity
      effects can become significant even for very thin two-layer films.

PMID- 15953615
TI  - The nucleobase-ascorbate transporter (NAT) signature motif in UapA defines the
      function of the purine translocation pathway.
AB  - UapA, a member of the NAT/NCS2 family, is a high affinity, high capacity, uric
      acid-xanthine/H+ symporter of Aspergillus nidulans. We have previously presented
      evidence showing that a highly conserved signature motif ([Q/E/P]408-N-X-G-X-X-X
      X-T-[R/K/G])417 is involved in UapA function. Here, we present a systematic
      mutational analysis of conserved residues in or close to the signature motif of
      UapA. We show that even the most conservative substitutions of residues Q408,
      N409 and G411 modify the kinetics and specificity of UapA, without affecting
      targeting in the plasma membrane. Q408 substitutions show that this residue
      determines both substrate binding and transport catalysis, possibly via
      interactions with position N9 of the imidazole ring of purines. Residue N409 is
      an irreplaceable residue necessary for transport catalysis, but is not involved
      in substrate binding. Residue G411 determines, indirectly, both the kinetics
      (K(m), V) and specificity of UapA, probably due to its particular property to
      confer local flexibility in the binding site of UapA. In silico predictions and a
      search in structural databases strongly suggest that the first part of the NAT
      signature motif of UapA (Q(408)NNG(411)) should form a loop, the structure of
      which is mostly affected by mutations in G411. Finally, substitutions of residues
      T416 and R417, despite being much better tolerated, can also affect the kinetics
      or the specificity of UapA. Our results show that the NAT signature motif defines
      the function of the UapA purine translocation pathway and strongly suggest that
      this might occur by determining the interactions of UapA with the imidazole part
      of purines.

PMID- 15953616
TI  - Structure of free MDM2 N-terminal domain reveals conformational adjustments that
      accompany p53-binding.
AB  - Critical to the inhibitory action of the oncogene product, MDM2, on the tumour
      suppressor, p53, is association of the N-terminal domain of MDM2 (MDM2N) with the
      transactivation domain of p53. The structure of MDM2N was previously solved with
      a p53-derived peptide, or small-molecule ligands, occupying its binding cleft,
      but no structure of the non-liganded MDM2N (i.e. the apo-form) has been reported.
      Here, we describe the solution structure and dynamics of apo-MDM2N and thus
      reveal the nature of the conformational changes in MDM2N that accompany binding
      of p53. The new structure suggests that p53 effects displacement of an N-terminal
      segment of apo-MDM2N that occludes access to the shallow end of the p53-binding
      cleft. MDM2N must also undergo an expansion upon binding, achieved through a
      rearrangement of its two pseudosymetrically related sub-domains resulting in
      outward displacements of the secondary structural elements that comprise the
      walls and floor of the p53-binding cleft. MDM2N becomes more rigid and stable
      upon binding p53. Conformational plasticity of the binding cleft of apo-MDM2N
      could allow the parent protein to bind specifically to several different
      partners, although, to date, all the known liganded structures of MDM2N are
      highly similar to one another. The results indicate that the more open
      conformation of the binding cleft of MDM2N observed in structures of complexes
      with small molecules and peptides is a more suitable one for ligand discovery and
      optimisation.

PMID- 15953614
TI  - K(ATP) channel therapeutics at the bedside.
AB  - The family of potassium channel openers regroups drugs that share the property of
      activating adenosine triphosphate-sensitive potassium (K(ATP)) channels,
      metabolic sensors responsible for adjusting membrane potential-dependent
      functions to match cellular energetic demands. K(ATP) channels, widely
      represented in metabolically-active tissue, are heteromultimers composed of an
      inwardly rectifying potassium channel pore and a regulatory sulfonylurea receptor
      subunit, the site of action of potassium channel opening drugs that promote
      channel activity by antagonizing ATP-induced pore inhibition. The activity of
      K(ATP) channels is critical in the cardiovascular adaptive response to stress,
      maintenance of neuronal electrical stability, and hormonal homeostasis. Thereby,
      K(ATP) channel openers have a unique therapeutic spectrum, ranging from
      applications in myopreservation and vasodilatation in patients with heart or
      vascular disease to potential clinical use as bronchodilators, bladder relaxants,
      islet cell protector, antiepileptics and promoters of hair growth. While the
      current experience in practice with potassium channel openers remains limited,
      multitude of ongoing investigations aims at defining the benefit of this emerging
      family of therapeutics in diverse disease conditions associated with metabolic
      distress.

PMID- 15953617
TI  - Crystal structure of a CRISP family Ca2+ -channel blocker derived from snake
      venom.
AB  - The cysteine-rich secretory proteins (CRISPs) are widely distributed in mammals,
      reptiles, amphibians and secernenteas, and are involved in a variety of
      biological reactions. Here we report the crystal structure of triflin, a snake
      venom derived blocker of high K(+)-induced artery contraction, at 2.4A
      resolution. Triflin consists of two domains. The first 163 residues form a large
      globular body with an alpha-beta-alpha sandwich core, which resembles
      pathogenesis-related proteins of group-1 (PR-1). Two glutamic acid-associated
      histidine residues are located in an elongated cleft. A Cd(2+) resides in this
      binding site, and forms a five-coordination sphere. The subsequent cysteine-rich
      domain adopts a rod-like shape, which is stabilized by five disulfide bridges.
      Hydrophobic residues, which may obstruct the target ion-channel, are exposed to
      the solvent. A concave surface, which is surrounded by these two domains, is also
      expected to play a significant role in the binding to the target receptor,
      leading to ion channel blockage. The C-terminal cysteine-rich region has a
      similar tertiary structure to voltage-gated potassium channel blocker toxins,
      such as BgK and ShK. These findings will contribute toward understanding the
      functions of the widely distributed CRISP family proteins.

PMID- 15953618
TI  - On the use of the Price equation.
AB  - This paper distinguishes two categories of questions that the Price equation can
      help us answer. The two different types of questions require two different
      disciplines that are related, but nonetheless move in opposite directions. These
      disciplines are probability theory on the one hand and statistical inference on
      the other. In the literature on the Price equation this distinction is not made.
      As a result of this, questions that require a probability model are regularly
      approached with statistical tools. In this paper, we examine the possibilities of
      the Price equation for answering questions of either type. By spending extra
      attention on mathematical formalities, we avoid the two disciplines to get mixed
      up. After that, we look at some examples, both from kin selection and from group
      selection, that show how the inappropriate use of statistical terminology can put
      us on the wrong track. Statements that are 'derived' with the help of the Price
      equation are, therefore, in many cases not the answers they seem to be. Going
      through the derivations in reverse can, however, be helpful as a guide how to
      build proper (probabilistic) models that do give answers.

PMID- 15953619
TI  - A short guide to the nomenclature of seven-transmembrane spanning receptors for
      lipid mediators.
AB  - The International Union of Pharmacology (IUPHAR) has established a Nomenclature
      Committee comprised of sub-committees of experts to evaluate types and subtypes
      of receptors and ion channels in an effort to establish universally accepted
      nomenclature [Vanhoutte, P.M., Barnard, E.A., Cosmides, G.J., Humphrey, P.P.,
      Spedding, M., Godfraind, T., 1994. International Union of Pharmacology Committee
      on Receptor Nomenclature and Drug Classification. Pharmacological Reviews 46, 111
      116]. This overview cites the reports of the IUPHAR subcommittees and other
      prominent review articles in an effort to compile receptors for lipid mediators
      that bind to and evoke their pharmacological responses via seven-transmembrane
      spanning, G-protein-coupled receptors.

PMID- 15953620
TI  - BCG modulation of anaphylactic antibody response, airway inflammation and lung
      hyperreactivity in genetically selected mouse strains (Selection IV-A).
AB  - The effect of Bacillus Calmette-Guerin (BCG) treatment in allergic pulmonary
      reaction was studied in mice genetically selected accordingly to a High (H-IVA)
      or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA)
      or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1
      anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar
      lavage and the compliance and conductance of respiratory system were evaluated. H
      IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit
      simultaneously the production of IgE, the bronchopulmonary inflammation and
      bronchial hyperresponsiveness in these genetically selected mice.

PMID- 15953621
TI  - Effect of preventive and regressive isosorbide 5-mononitrate treatment on
      catecholamine levels in plasma, platelets, adrenals, left ventricle and aorta in
      cyclosporin A-induced hypertensive rats.
AB  - Increased vascular reactivity associated with cyclosporin A (CsA)-induced
      arterial hypertension might result from increased vasoconstriction and/or
      decreased vasodilatation. The administration of organic NO donors could have
      beneficial effects by the NO-cGMP reposition, but there is the risk of
      sympathetic nervous system worsening by neuro-hormonal counter-regulation. We
      evaluate the effect of preventive and regressive (curative) isosorbide 5
      mononitrate (Is-5-Mn) treatment on blood pressures and on plasma, platelets,
      adrenals, left ventricle and aorta norepinephrine (NE) and epinephrine (E)
      contents, assessed by HPLC, in CsA-induced hypertensive rats. Five rat groups
      were tested: control (orange juice), CsA (5 mg/kg/day) and Is-5-Mn (150
      mg/kg/day, bid) groups were treated for 7 weeks; preventive group (Is-5-Mn+CsA):
      Is-5-Mn during 2 weeks plus 7 weeks of Is-5-Mn+CsA; regressive group (CsA+Is-5
      Mn): CsA during 7 weeks plus 5 weeks of CsA+Is-5-Mn. The increased BP in the CsA
      group was prevented, but was not reverted, by concomitant Is-5-Mn treatment. In
      the CsA-treated rats, there was a noticeable decrease in left ventricle NE and E
      contents and aorta NE levels and a moderate increase in circulating
      catecholamines, without significant effect in the adrenals values. When Is-5-Mn
      was preventively used, the CsA-induced effect on left ventricle and aorta was
      prevented. Concomitantly, however, the plasma-platelet catecholamine balance was
      disrupted, accumulating NE in plasma, whereas E increased in aorta, mimic the
      single Is-5-Mn-treated group. In opposition, in the group used as regressive Is-5
      Mn therapy, the adrenals contents were higher compared with the CsA-group and,
      simultaneously, the CsA-evoked effects on circulating, left ventricle and aorta
      catecholamines were not reverted. In conclusion, regressive Is-5-Mn therapy was
      unable to attenuate CsA-induced catecholamine changes and BP values even
      worsened. On the contrary, preventive Is-5-Mn treatment prevented the
      catecholamine changes on left ventricle and aorta, but increased plasma NE and
      aorta E accumulation. Even though with those effects, hypertension development
      was totally prevented, suggesting that peripheral SNS per se cannot fully explain
      CsA-induced hypertension. Furthermore, Is-5-Mn might produce beneficial effects
      only if preventively employed but, considering the changes on peripheral
      catecholamine contents, a judicious evaluation of the nitrate therapy impact is
      recommended in order to avoid further deleterious effects.

PMID- 15953622
TI  - Central and peripheral interactions between endocannabinoids and steroids, and
      implications for drug dependence.
AB  - Endocannabinoids are biologically active amides, esters and ether of long chain
      polyunsaturated fatty acids. They interact with several neurotransmitters in the
      central nervous system (CNS), and with various signaling molecules (including
      cytokines) in the periphery. Critical interactions have emerged also with
      steroids, another group of well-known bioactive lipids, both centrally and
      peripherally. Here, I briefly review the targets of the combined action of
      endocannabinoids and steroids, and the available evidence concerning the direct
      regulation by the latter compounds of the proteins of the endocannabinoid system
      (ES). In addition, I discuss recent examples of endocannabinoids and steroids
      working together in the central nervous system and in the periphery, which
      allowed to disclose some molecular details of the interactions between these two
      groups of lipids. Taken together, available data suggest that steroids can
      modulate the endocannabinoid tone, through genomic or nongenomic regulation, and
      that endocannabinoids can complement the biological activity of steroids. In this
      line, the issues concerning the tissue- and species-specificity of the
      endocannabinoid-steroid interface, and the possibility that also endocannabinoids
      may modulate steroid metabolism, are addressed. Finally, I present the hypothesis
      that retrograde endocannabinoid signaling, by reducing striatal glutamate
      release, may be part of the molecular events responsible for the influence of
      steroids on drug abuse.

PMID- 15953623
TI  - Necrodane monoterpenoids from Lavandula luisieri.
AB  - Four new irregular monoterpenoids were identified in the essential oil of
      Lavandula luisieri (Rozeira) Riv. Mart., a Labiatae endemic to the Iberian
      Peninsula. By means of spectroscopic and chemical methods, they were
      characterised as 3,5-dimethylene-1,4,4-trimethylcyclopentene, 5-methylene-2,3,4,4
      tetramethylcyclopent-2-enone, 3,4,5,5-tetramethylcyclopenta-1,3
      dienecarboxaldehyde and 3,4,5,5-tetramethylcyclopenta-1,3-dienecarboxylic acid.
      L. luisieri essential oil and extract showed a good activity against Candida
      albicans and gram positive bacteria: Staphylococcus aureus, S. epidermidis and S.
      pyogenes.

PMID- 15953624
TI  - Disrupted G1 to S phase clearance via cyclin signaling impairs liver tissue
      repair in thioacetamide-treated type 1 diabetic rats.
AB  - Previously we reported that a nonlethal dose of thioacetamide (TA, 300 mg/kg)
      causes 90% mortality in type 1 diabetic (DB) rats because of irreversible acute
      liver injury owing to inhibited hepatic tissue repair, primarily due to blockage
      of G(0) to S phase progression of cell division cycle. On the other hand, DB rats
      receiving 30 mg TA/kg exhibited equal initial liver injury and delayed tissue
      repair compared to nondiabetic (NDB) rats receiving 300 mg TA/kg, resulting in a
      delay in recovery from liver injury and survival. The objective of the present
      study was to test the hypothesis that impaired cyclin-regulated progression of
      G(1) to S phase of the cell cycle may explain inhibited liver tissue repair,
      hepatic failure, and death, contrasted with delayed liver tissue repair but
      survival observed in the DB rats receiving 300 in contrast to 30 mg TA/kg. In the
      TA-treated NDB rats sustained MAPKs and cyclin expression resulted in higher
      phosphorylation of retinoblastoma (pRb), explaining prompt tissue repair and
      survival. In contrast, DB rats receiving the same dose of TA (300 mg/kg)
      exhibited suppressed MAPKs and cyclin expression that led to inhibition of pRb,
      inhibited tissue repair, and death. On the other hand, DB rats receiving 30 mg
      TA/kg exhibited delayed up regulation of MAPK signaling that delayed the
      expression of CD1 and pRb, explaining delayed stimulation of tissue repair
      observed in this group. In conclusion, the hepatotoxicant TA has a dose-dependent
      adverse effect on cyclin-regulated pRb signaling: the lower dose causes a
      recoverable delay, whereas the higher dose inhibits it with corresponding effect
      on the ultimate outcomes on hepatic tissue repair; this dose-dependent adverse
      effect is substantially shifted to the left of the dose response curve in
      diabetes.

PMID- 15953625
TI  - Broccoli and watercress suppress matrix metalloproteinase-9 activity and
      invasiveness of human MDA-MB-231 breast cancer cells.
AB  - A high dietary intake of cruciferous vegetables has been associated with a
      reduction in numerous human pathologies particularly cancer. In the current
      study, we examined the inhibitory effects of broccoli (Brassica oleracea var.
      italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix
      metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant
      overexpression of matrix metalloproteinases, including metalloproteinase-9, is
      associated with increased invasive potential in cancer cell lines. Our results
      demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9
      activity and invasiveness in a concentration dependent manner as determined by
      zymographic analysis. Furthermore, fractionation of individual extracts followed
      by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the
      inhibitory effects of each vegetable were associated with the presence of 4
      methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates.
      Taken together, our data indicate that isothiocyanates derived form broccoli and
      Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive
      potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory
      effects observed in the current study may contribute to the suppression of
      carcinogenesis by diets high in cruciferous vegetables.

PMID- 15953626
TI  - Treatment of hazardous shipyard wastewater using dolomitic sorbents.
AB  - Hazardous shipyard wastewater is a worldwide problem, arising from ship repair.
      In this study an experimental programme was undertaken to establish the
      suitability of dolomite and dolomitic sorbent materials to remove contaminants
      from wastewater arising from a commercial shipyard. Experimental data indicate
      that dolomite and dolomitic sorbents have the ability to significantly reduce the
      COD concentration of the shipyard effluent (98% reduction). The data gained from
      trials at a shipyard indicated that the dolomite treatment process could be
      undertaken in a 8000 L pilot scale reaction vessel. Analysis of the wastewater
      using ICP-MS during the pilot trial indicated that the dolomite significantly
      reduced the concentrations of metallic impurities. The concentration of Sn ions,
      which is indicative of organo-tin complexes commonly found in shipyard
      wastewater, was reduced by 80% from its initial concentration in the pilot trial.
      The mechanism for the removal process using dolomite has been ascribed to a metal
      complexation/sorption process.

PMID- 15953627
TI  - Angiotensin II induces the expression of tissue factor and its mechanism in human
      monocytes.
AB  - The renin-angiotensin system (RAS) is linked with the vascular motion and the
      secretion of aldosterone. The purpose of the present study was to elucidate
      whether angiotensin II (Ang II) induces monocytes (Mo) to express tissue factor
      (TF) and if Ang II subtype 1 receptor (AT1R) antagonists inhibit the effect of
      Ang II. The roles of different intracellular signal transduction pathways and
      IkappaB/NF-kappaB in Ang II-induced TF expression of Mo were also studied to
      explore the mechanisms involved. Mo were isolated from heparinized human blood by
      a two-step gradient centrifugation, cultured in RPMI-1640 and exposed to Ang II
      and other test reagents. Mo TF activity and TF antigen were determined with a one
      stage clotting method and ELISA, respectively, after the culture. Reverse
      transcription-polymerase chain reaction (RT-PCR) was used to detect the TF mRNA
      levels in Mo. The level of IkappaBalpha in Mo was detected by Western blot
      analysis. Electrophoresis mobility shift assay (EMSA) was performed to evaluate
      the binding activity of NF-kappaB in Mo. The experiment results are as follows:
      (1) Ang II (10(-10)-10(-7) M) induced Mo to express TF activity but had no marked
      effect on other mononuclear cells. Ang II 10(-10)-10(-7) M) also caused increased
      TF mRNA expression and TF antigen from Mo in a dose-dependent manner. The TF
      antigen of Mo was elevated at 4 h after Mo was exposed to Ang II (10(-7) M) in
      culture, reached the peak at 6 h, and then declined from 12 h. The changes of TF
      activity were positively correlated with those of TF antigen. TF mRNA expression
      was elevated at 1 h, peaked at 3 h, and declined after 8 h. (2) Losartan (10(-6)
      10(-5) M) significantly inhibited the stimulative effects of Ang II on TF
      activity, TF antigen and TF mRNA in Mo in a dose-dependent manner. (3) The
      protein kinase C (PKC) inhibitor, staurosporine, and the protein tyrosine kinase
      (PTK) inhibitor, genistein, both lowered TF levels in Mo, but the inhibitory
      effect of staurosporine was stronger than that of genistein. The effect of
      mitogen-activated protein kinase (MAPK) inhibitor, U0126, on monocytic TF
      expression was not significant. (4) Western blot analysis revealed that after Ang
      II (10(-7) M)exposure, levels of IkappaBalpha began to decrease at 15 min,
      reached a nadir at 60 min (P<.01), and recovered at 180 min. (5) EMSA showed that
      NF-kappaB binding activity started to increase at 15 min, reached a peak at 60
      min, and returned to baseline at 180 min. The present data suggest that Ang II
      can directly induce TF expression in human Mo and this effect is mediated by
      AT1R. PKC may play the most important role in Ang II-induced TF expression among
      the three signal pathways detected. In addition, activation of NF-kappaB is also
      involved in the TF expression of Mo induced by Ang II.

PMID- 15953628
TI  - Ebselen attenuates haloperidol-induced orofacial dyskinesia and oxidative stress
      in rat brain.
AB  - Haloperidol-induced orofacial dyskinesia is an animal model of tardive dyskinesia
      whose pathophysiology has been related to basal ganglia oxidative stress. In this
      study the authors examined whether ebselen, an antioxidant organochalcogen with
      glutatione peroxidase-like activity, changes the behavioral and neurochemical
      effect of sub-chronic haloperidol administration. Haloperidol administered (12
      mg/kg/week, sc) for 4 weeks caused a significant increase in vacuous chewing
      movements (VCMs), tongue protrusion (TP) and the duration of facial twitching
      (FT) observed in 4 weekly evaluations (p<0.05). Ebselen (30 mg/kg, ip),
      administered every other day, along with haloperidol (12 mg/kg/week, sc) once
      weekly, reversed the increase of VCMs and FT in four weekly evaluations (p<0.05),
      while TP frequency was reverted in the 2nd, 3rd, and 4th week. After the
      treatments and behavioral observation, biochemical parameters in segments of the
      brain were analyzed. Haloperidol significantly increased the thiobarbituric acid
      reactive species (TBARS) levels in the cortex, striatum and subcortical parts of
      the brain. The co-administration of ebselen reversed the effect of haloperidol on
      TBARS production in cortex and striatum. The results of the present study clearly
      indicate that ebselen has a protective role against haloperidol-induced orofacial
      dyskinesia and reverses the increase in TBARS production caused by haloperidol
      administration. Consequently, the use of ebselen as a therapeutic agent for the
      treatment of tardive dyskinesia should be considered.

PMID- 15953629
TI  - Vaginal and cervical modifications during the estrus cycle in the domestic cat.
AB  - A thorough knowledge of the genital tract anatomy and vaginal and cervical
      modifications during the phases of estrus cycle of the female cat is necessary to
      enhance success of assisted feline reproductive technologies or for other
      diagnostic or therapeutic purposes. There are few studies of the gross anatomy of
      the genital tract in the queen. The vestibule is large in comparison to the
      vagina; the latter has a narrow lumen, which is further constricted by the
      prominent dorsal median fold. The cervix is oriented obliquely between the
      uterine body and vagina. Vaginal and cervical changes in association with the
      estrous cycle have been reported in some species and two recent studies
      investigated this aspect in the cat. This paper reviews the relevant literature,
      with particular emphasis on recent studies.

PMID- 15953630
TI  - Cellular associations and the differential spermiogram: making sense of stallion
      spermatozoal morphology.
AB  - Morphologic assessment of spermatozoa is one of the most objective measures in a
      Breeding Soundness Examination of a stallion. There are different systems for
      morphologic assessment of spermatozoa. The objectives of this article are to
      review spermatogenesis, describe clinical sample preparation, discuss previous
      methods of morphologic classification and explain the use of a differential
      spermiogram. The advantages of the differential spermiogram method of analysis
      are discussed, along with its use in delineating intrinsic and extrinsic
      disturbances in spermatogenesis. Case examples of specific cellular associations
      and their diagnostic relevance are discussed.

PMID- 15953631
TI  - Analysis of gene expression in non-regressed and regressed bovine corpus luteum
      tissue using a customized ovarian cDNA array.
AB  - The lifespan of the bovine corpus luteum (CL) is an important factor in the
      control of normal ovarian cyclicity and the establishment and maintenance of
      pregnancy. There is increasing evidence that CL lifespan is regulated by
      alternative expression of genes that promote or inhibit luteolysis. To gain
      further insights into these events a 434 character ovarian cDNA array comprising
      genes attributed to key aspects of CL function including more than 100 anonymous
      expressed sequence tags (ESTs) was constructed and screened with alpha(33)P dATP
      labeled RNA isolated from non-regressed (n=6) and regressed (n=6) CL tissue.
      Significance analysis of microarrays (SAM) identified 15 genes that changed
      expression 1.7-fold or more with a false discovery rate of <5%. The
      differentially expressed genes encoded enzymes involved in steroid biosynthesis
      and oxygen radical metabolism and proteins involved in extracellular matrix
      remodeling, apoptosis and cell structure. Results for five of the differentially
      expressed genes including matrix gla protein and collagen alpha1(I)
      (extracellular matrix), glutathione-S-transferase alpha I (oxygen metabolism),
      clusterin (apoptosis) and scavenger receptor BI (steroid biosynthesis) were
      confirmed by Northern blot analysis and found to be significantly different
      (P<0.01) between non-regressed and regressed CL tissue. Collectively this study
      identified genes with recognized roles in CL regression, genes with potential
      roles in this process and genes whose function have yet to be defined in this
      event.

PMID- 15953632
TI  - In vitro characterization of leukocyte mimetic for targeting therapeutics to the
      endothelium using two receptors.
AB  - Selectins (E- and P-selectin) and other endothelial expressed leukocyte adhesion
      molecules (ELAMs) are potential targets for site-specific delivery of
      therapeutics to the vascular endothelium due to their specific and highly
      regulated expression in vascular disease. It was recently shown that degradable
      microspheres coated with antibodies against E-selectin or other ELAMs can target
      inflammation in vivo. However, targeting ELAMs alone cannot differentiate between
      normal and diseased state, as a basal level of these LAMs are expressed on
      endothelium in healthy tissues. Furthermore, leukocytes usually employ two
      separate adhesion molecules in parallel to home to diseased tissues, and we
      recently quantified the advantages of a two-receptor display for the targeting of
      leukocyte mimetics (Eniola AO, Willcox PJ, Hammer DA. Interplay between rolling
      and firm adhesion elucidated with a cell-free system engineered with two distinct
      receptor-ligand pairs. Biophys J 2003;85:2720-31). Here, we describe a leukocyte
      mimetic for targeting therapeutics to the vasculature in inflammatory diseases
      via two receptors, selectin and intercellular cell adhesion molecule-1 (ICAM-1),
      where biodegradable, polymer microspheres were co-functionalized with the
      selectin ligand, sialyl Lewis(X) (sLe(X)), and an antibody against ICAM-1, anti
      ICAM-1 (aICAM-1). These two-receptor targeted particles, at given ratios of
      sLe(X)/aICAM-1, firmly adhere to substrate surface in flow only when both
      targeting ligands can interact with their respective receptors, mimicking the
      multi-step in vivo leukocyte adhesion in inflammation. Thus, we have faithfully
      recreated the specificity and extent of leukocyte adhesion in a platform that can
      allow for local delivery of therapeutics.

PMID- 15953633
TI  - Mathematical modelling of the distribution of newly formed bone in bone tissue
      engineering.
AB  - New bone formation in bone substitutes is usually investigated by
      histomorphometric global analysis. This study provides a novel mathematical
      modelling approach of new bone formation in the use of osteoinductive and
      functionalized biomaterials for bone tissue engineering. We discuss here the
      repartition and the probability to get new bone formation inside Biphasic Calcium
      Phosphate (BCP) loaded with autologous osteogenic cells, functionalized with a
      cyclo RGD peptide, after implantation in rabbits for 2 and 4 weeks. This local
      analysis allowed us to complement classical global findings and to demonstrate
      that after 2 weeks of implantation, the probability of new bone formation was
      significantly higher in RGD-grafted BCP and that new formed bone was largely
      distributed from the edge to the centre of the implant. While no significant
      differences were obtained after 4 weeks of implantation between RGD-grafted and
      non-grafted materials, distribution of new bone formation inside RGD-grafted
      materials was significantly more homogeneous as demonstrated by our mathematical
      modelling approach. In conclusion, local analysis of new bone formation inside
      macroporous substitutes coupled with mathematical modelling constitutes a
      potential quantitative approach for the evaluation of the osteoconductive and
      osteoinductive characteristics of such biomaterials.

PMID- 15953634
TI  - A histological study of fetoscopic membrane defects to document membrane healing.
AB  - OBJECTIVE: To evaluate the rate of spontaneous healing in human fetal membranes
      after fetoscopy. STUDY DESIGN: Membranes from patients that had undergone
      fetoscopic interventions and delivered in one of the two treatment centers were
      included in the study. The membranes were examined macroscopically for any
      remaining defects and if present, the size of the defect in chorion and amnion
      was measured. Subsequently, the defect was excised and stained with HE for
      histological evaluation. Additional immunohistochemical staining was performed
      with Ki-67, cytokeratin and vimentin. The proliferation index (percentage of
      proliferating cells) was calculated in amnion and chorion. RESULTS: Nineteen
      membrane defects were included in the study. The median time interval between
      invasive procedures and delivery was 60 days (range 3-112). All fetoscopic
      defects (n=19) could be identified in the gestational sac and in none spontaneous
      closure had occurred. Proliferation indices as measured by inmunohistochemistry
      were very low (median 2.8%, range 0-7%) in the chorion and 0% in the amnion.
      CONCLUSION: No evidence of spontaneous membrane healing was found after
      fetoscopic procedures, suggesting that the membrane defect normally persists
      until delivery. Absence of amniotic fluid leakage after invasive procedures may
      be based on mechanisms other than histologic membrane repair.

PMID- 15953635
TI  - Scenario-based simulation of runoff-related pesticide entries into small streams
      on a landscape level.
AB  - The prediction of runoff-related pesticide entry into surface waters on a
      landscape level usually requires considerable efforts with regard to input data,
      time, and personnel. Therefore, the need for an easy to use simulation tool with
      easily accessible input data, for example from already existing public sources,
      is obvious. In this paper, we present a simulation tool for the simulation of
      pesticide entry from arable land into adjacent streams. Our aim was to develop a
      tool applicable on the landscape level using "real world data" from numerous
      sites and for the simulation of parameter case studies concerning particular
      parameters at single sites. We used the ratio of exposure to toxicity (REXTOX)
      model proposed by the OECD, which had been successfully validated in the study
      area as part of a previous study and which was extended to calculate pesticide
      concentrations in adjacent streams. We simulated the pesticide entry on the
      landscape level at 737 sites in small streams situated in the central lowland of
      Germany with winter wheat, barley, and sugar beat as the main agricultural crops.
      A sensitivity analysis indicated that the most significant model parameters were
      the width of the no-application zone and the degree of plant interception. The
      simulation was carried out for the 15 most frequently detected substances found
      in the study area using eight different environmental scenarios, covering
      variation of the width of the no-application zone, climate, and seasonal
      scenarios. The highest in-stream concentrations were predicted for a scenario
      using no (0m) buffer zone in conjunction with increased precipitation. According
      to the predicted concentrations, the risk for the aquatic communities was
      estimated based on standard toxicity tests and the application of a safety
      factor. The simulation results are presented both by means of risk maps for the
      study area showing the simulated pesticide concentration and the resulting
      ecological risk for numerous sites under varying scenarios and by case study
      diagrams with focus on the model behavior under the influence of single
      parameters. Risk maps confirmed the importance of no-application (buffer) zones
      for the levels of pesticide input. They also indicated the importance of the
      existing no-application zones for certain compounds and in some cases the need
      for a further evaluation of these regulations. The simulation tool was
      implemented as a standard PC software combining the REXTOX model with a
      geographical information system and can be used on any current personal computer.
      All input data was taken from public sources of German authorities. With little
      effort the tool should be applicable for other areas with similar data quality.

PMID- 15953636
TI  - External versus endoscopic dacryocystorhinostomy for acquired nasolacrimal duct
      obstruction in a tertiary referral center.
AB  - PURPOSE: To compare success rates of external dacryocystorhinostomy (DCR) and
      endoscopic endonasal DCR for acquired nasolacrimal duct obstruction (NLDO).
      DESIGN: Retrospective, comparative, nonrandomized clinical study. PARTICIPANTS:
      One hundred forty-three patients (176 surgeries) operated for acquired NLDO.
      METHODS: A review of electronic medical records of patients with acquired NLDO
      who underwent DCR at the Jules Stein Eye Institute from 1999 to 2004 was
      performed. Data regarding the lacrimal drainage system, comprehensive eye
      examination, surgical outcome, and postoperative nasal endoscopy were analyzed.
      MAIN OUTCOME MEASURES: Surgery failure was defined as (1) no marked improvement
      in tearing or any episode of postoperative dacryocystitis, (2) inability to
      irrigate the lacrimal system postoperatively, and (3) postoperative nasal
      endoscopy with scarring in the intranasal osteotomy or no visualization of
      fluorescein dye. Postoperative nasal endoscopy was performed in all failed cases
      and in >50% of all patients. RESULTS: One hundred forty-three patients (48 male
      and 95 female; mean age, 63 years) underwent 176 DCR surgeries for acquired NLDO.
      Success was achieved in 135 cases (76.7%), and failure in 41 (23.3%). Of the 41
      failed cases, anatomical obstruction at the fistula site was found in 20 (49% of
      failed cases), whereas functional failure with no evidence of obstruction was
      found in 21 (51%). Surgery revision was performed in 22 cases (12.5%), but it was
      successful in only 9 (5.1%); patients who failed the first revision were likely
      to fail additional revisions (P = 0.02). History of facial trauma was associated
      with surgery failure. In our patients, endoscopic DCR (86 cases) had a
      significantly higher success rate than external DCR (90 cases), 84% versus 70% (P
      = 0.03). Complications included 1 patient with nose bleeding on the first
      postoperative day that resolved with nasal packing and 2 patients with sump
      syndrome that resolved after endoscopic revision. CONCLUSIONS: The success rate
      of DCR for acquired NLDO in our group of patients was 77%, lower than reported in
      previous studies, with endoscopic surgery showing better results. Success rates
      of revision surgery were relatively low (<50%), and patients who fail the first
      revision are not likely to benefit from additional revisions.

PMID- 15953637
TI  - The incidence of endophthalmitis after cataract surgery among the U.S. Medicare
      population increased between 1994 and 2001.
AB  - OBJECTIVE: To estimate the annual incidence rate of presumed endophthalmitis
      after cataract surgery, evaluate any changes in this rate over time, and examine
      demographic risk factors for endophthalmitis after cataract surgery. DESIGN:
      Population-based review of Medicare beneficiary claims data. DATA SOURCE:
      Medicare 5% sample beneficiary data files for inpatient and outpatient claims
      from 1994 through 2001 were examined to identify all cataract surgeries and
      subsequent cases of presumed endophthalmitis after cataract surgery. METHODS: All
      cataract surgery and presumed endophthalmitis cases after cataract surgery were
      identified based on claims submitted. The annual rate of presumed endophthalmitis
      after cataract surgery was calculated, and demographic risk factors for
      endophthalmitis were examined using multivariate models. MAIN OUTCOME MEASURES:
      Incidence rate of endophthalmitis after cataract surgery and prevalence of
      demographic risk factors for endophthalmitis over an 8-year period. RESULTS: One
      thousand twenty-six cases of presumed endophthalmitis occurred after 477,627
      cataract surgeries, yielding an incidence rate of 2.15 per 1000 for this 8-year
      period. Rates of endophthalmitis adjusted for age, gender, and race were
      significantly higher in 1998 to 2001 than in earlier years (relative risk [RR],
      1.41; 95% confidence interval [CI], 1.24-1.60). Older age and black race also
      were associated with increased risk of endophthalmitis (RR, 1.83; 95% CI, 1.19
      2.81; age, > or =90 years, and RR, 1.30; 95% CI, 1.02-1.65, respectively).
      CONCLUSIONS: Analysis of Medicare claims data suggests that the incidence of
      endophthalmitis after cataract surgery has been increasing, but does not provide
      an explanation for this occurrence. An increase in the incidence of
      endophthalmitis after cataract surgery is of concern, because cataract surgery is
      the most commonly performed operation in the United States, and the number of
      cataract surgeries performed annually will likely increase substantially over the
      coming decades due to the aging of the U.S. population.

PMID- 15953638
TI  - Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1,
      causes cone, cone-rod, and macular dystrophy.
AB  - PURPOSE: To determine the underlying molecular genetic basis of a retinal
      dystrophy identified in a 4-generation family and to examine the phenotype and
      the degree of intrafamilial variability. DESIGN: Prospective case series.
      PARTICIPANTS: Six affected individuals from a nonconsanguineous British family.
      METHODS: Detailed ophthalmologic examination, color fundus photography,
      autofluorescence imaging, and electrophysiologic assessment were performed. Blood
      samples were taken for DNA extraction, and mutation screening of GUCA1A, the gene
      encoding guanylate cyclase-activating protein 1 (GCAP1), was undertaken. RESULTS:
      All affected subjects complained of mild photophobia and reduced central and
      color vision. Onset was between the third and fifth decade, with subsequent
      gradual deterioration of visual acuity and color vision. Visual acuity ranged
      between 6/9 and counting fingers. Color vision was either absent or markedly
      reduced along all 3 color axes. A range of macular appearances was seen, varying
      from mild retinal pigment epithelial disturbance to extensive atrophy.
      Electrophysiologic testing revealed a range of electrophysiologic abnormalities:
      isolated cone electroretinography abnormalities, reduced cone and rod responses
      (with cone loss greater than rod), and isolated macular dysfunction. The 4 coding
      exons of GUCA1A were screened for mutations in affected and unaffected family
      members. A single transition, A319G, causing a nonconservative missense
      substitution, Tyr99Cys, segregated uniquely in all affected subjects.
      CONCLUSIONS: The Tyr99Cys GUCA1A mutation has been previously shown to cause
      autosomal dominant progressive cone dystrophy. This is the first report of this
      mutation also causing both cone-rod dystrophy and isolated macular dysfunction.
      The phenotypic variation described here exemplifies the intrafamilial
      heterogeneity of retinal dysfunction that can be observed in persons harboring
      the same mutation and chromosomal segment.

PMID- 15953639
TI  - Botulinum toxin for palliative treatment of epiphora in a patient with
      canalicular obstruction.
AB  - OBJECTIVE: To describe the use of botulinum toxin injection of the lacrimal gland
      for palliative treatment of epiphora secondary to canalicular obstruction from
      docetaxel therapy. DESIGN: Case report. INTERVENTION: A 50-year-old female with
      bilateral canalicular obstruction secondary to docetaxel therapy received
      botulinum toxin injections (5 units each) into the lacrimal glands of both eyes.
      RESULTS: Symptomatic epiphora of the affected eyes was reduced after 2 weeks. No
      side effects were observed. CONCLUSIONS: Botulinum toxin injection of the
      lacrimal gland is an effective palliative treatment for epiphora secondary to
      canalicular obstruction from docetaxel therapy.

PMID- 15953640
TI  - X-linked cone dysfunction syndrome with myopia and protanopia.
AB  - PURPOSE: To perform a detailed clinical, psychophysical, and molecular assessment
      of members of 4 families with an unusual X-linked cone dysfunction syndrome
      associated with myopia. PARTICIPANTS: Affected and unaffected members of 4
      British nonconsanguineous families. METHODS: Subjects underwent both detailed
      clinical examination and psychophysical testing. After informed consent was
      obtained, blood samples were taken for DNA extraction, and molecular genetic
      analysis was performed. The strategy for molecular analysis was to amplify the
      coding regions of the long and middle wavelength-sensitive cone opsin genes and
      the upstream locus control region by polymerase chain reaction and to examine
      these fragments for mutations by sequencing of DNA. RESULTS: The phenotype was
      almost identical in all 4 families, consisting of moderate to high myopia,
      astigmatism, moderately reduced acuity, and normal fundi. Electroretinography
      showed abnormal cone but normal rod responses. Psychophysical testing showed a
      selective impairment of long cones in combination with well-preserved middle cone
      and short cone function. There was no evidence to suggest that the phenotype was
      progressive. Molecular analysis of the X-linked opsin gene array in the 4
      families indicated that affected males have inherited the same X-chromosome from
      their mother. In 2 families, a long/middle hybrid gene was detected. In a third
      family, the commonly described deleterious Cys203Arg amino acid substitution was
      identified in both the long and middle opsin genes. In the fourth family, the
      only abnormality was absence of a middle opsin exon 2; the cause of the
      protanopia in this family is uncertain. CONCLUSIONS: The X-linked cone
      dysfunction syndrome associated with myopia and dichromacy described here has
      many similarities to Bornholm eye disease, a condition previously mapped to Xq28.
      Except for the Cys203Arg substitution in one family, no alterations in the opsin
      gene array were identified that could underlie the cone dysfunction. It is
      therefore possible that the cone dysfunction may have a genetic origin different
      from that of the dichromacy.

PMID- 15953641
TI  - The association between myopia and various subtypes of lens opacity: SEE
      (Salisbury Eye Evaluation) project.
AB  - PURPOSE: To establish the relationship between myopia and lens opacity. DESIGN:
      Population-based cross-sectional study. PARTICIPANTS: Two thousand five hundred
      twenty participants from the Salisbury Eye Evaluation aged 65 to 84 years.
      METHODS: Participants filled out questionnaires regarding medical history, social
      habits, and a detailed history of distance spectacle wear. They underwent a full
      ocular examination. Lens photographs were taken for assessment of lens opacity
      using the Wilmer grading system. Multivariate logistic regression models using
      generalized estimating equations were used to analyze the relationship between
      lens opacity type and degree of myopia, while accounting for potential
      confounders. MAIN OUTCOME MEASURES: Presence of posterior subcapsular opacity,
      cortical opacity, or nuclear opacity. RESULTS: Significant associations were
      found between myopia and both nuclear and posterior subcapsular opacities. For
      nuclear opacity, the odds ratios (ORs) were 2.25 for myopia between -0.50
      diopters (D) and -1.99 D (P<0.001), 3.65 for myopia between -2.00 D and -3.99 D
      (P<0.001), 4.54 for myopia between -4.00 D and -5.99 D (P<0.001), and 3.61 for
      myopia -6.00 D or more (P = 0.002). For posterior subcapsular cataracts, ORs were
      1.59 for myopia between -0.50 D and -1.99 D (P = 0.11), 3.22 for myopia between 
      2.00 D and -3.99 D (P = 0.002), 5.36 for myopia between -4.00 D and -5.99 D
      (P<0.001), and 12.34 for myopia -6.00 D or more (P<0.001). No association was
      found between myopia and cortical opacity. The association between posterior
      subcapsular opacity and myopia was equally strong for those wearing glasses by
      age 21 years and for those without glasses; for nuclear opacity, significantly
      higher ORs were found for myopes who started wearing glasses after age 21.
      CONCLUSIONS: These results confirm the previously reported association between
      myopia, posterior subcapsular opacity, and nuclear opacity. Furthermore, the
      strong association between early spectacle wear and posterior subcapsular opacity
      among myopes, absent for nuclear opacity, suggests that myopia may precede
      opacity in the case of posterior subcapsular opacity, but not nuclear opacity.
      Measures of association between posterior subcapsular opacity and myopia were
      stronger in the current study than have previously been found. Longitudinal
      studies to confirm the association are warranted.

PMID- 15953642
TI  - Nonvitrectomizing vitreous surgery for epiretinal membrane long-term follow-up.
AB  - PURPOSE: To report the long-term follow-up results of nonvitrectomizing vitreous
      surgery for idiopathic epiretinal membrane (ERM). DESIGN: Nonrandomized
      comparative case series. PARTICIPANTS: Thirty patients were followed up for at
      least 5 years after nonvitrectomizing vitreous surgery. INTERVENTION: Epiretinal
      membranes were peeled without infusion of balanced salt solution and removal of
      the vitreous. The data from the fellow eye was the control data. MAIN OUTCOME
      MEASURES: We examined the visual acuities (VAs), objective refractions, and slit
      lamp and Scheimpflug photographs from the preoperative and the final examinations
      of both eyes. Quantitative assessment of the progression of nuclear sclerosis was
      performed by densitometry analysis using Scheimpflug photography. The recurrence
      rate of ERM was determined. RESULTS: The follow-up periods ranged from 60 to 102
      months (mean+/-standard deviation, 72.2+/-11.0 months). The patient ages ranged
      from 52 to 76 years (68.8+/-6.3 years). The final VA improved or stabilized
      within 2 lines in 29 of 30 eyes (96.7%). No unilateral progression of nuclear
      sclerosis occurred in any cases. The mean preoperative and postoperative
      refractions without additional surgery were -0.4+/-2.9 diopters (D) and -0.2+/
      3.0 D in the operated eyes, respectively, and -0.2+/-2.5 D and 0.1+/-2.4 D,
      respectively, in the unoperated fellow eyes. The mean differences in the
      refractive error between both eyes (operated eye data minus fellow eye data) were
      -0.2+/-0.7 D before surgery and -0.3+/-0.8 D after surgery (P = 0.319, paired t
      test). The mean preoperative and postoperative nuclear densities in 16 patients
      were 69+/-14 nuclear density units (NDUs) and 76+/-12 NDUs in the operated eyes
      and 71+/-14 NDUs and 78+/-14 NDUs in the fellow eyes, respectively. The mean
      preoperative and postoperative differences in nuclear densities in both eyes were
      -2+/-2 NDUs and -2+/-5 NDUs, respectively (P = 0.836, paired t test). The ERM
      recurred in 10 eyes (33%), and 3 eyes underwent conventional vitrectomy combined
      with cataract surgery. CONCLUSIONS: Unilateral nuclear sclerosis did not progress
      for at least 5 years after nonvitrectomizing vitreous surgery. The recurrence
      rate of ERM appeared to be higher than that after conventional vitreous surgery.

PMID- 15953643
TI  - Improved safety in contemporary LASIK.
AB  - PURPOSE: To examine the risk of serious visual loss in contemporary LASIK.
      DESIGN: Retrospective, noncomparative, consecutive case series combined with a
      structured literature review and comparison with historical controls.
      PARTICIPANTS: One thousand consecutive cases of LASIK performed from January 2000
      to January 2004 by 1 surgeon. One thousand nine hundred eighty-two cases with 6
      month review data in postmillennial Food and Drug Administration (FDA) trials of
      LASIK for myopia and astigmatism and 5203 patients with 6 month review data in
      similar premillennial FDA trials. METHODS: LASIK was performed with the Hansatome
      microkeratome and a VISX Star (S2, S3, or S4) laser. There were 899 myopic
      treatments (spherical equivalent < or =-10.5 diopters [D]; average -4.2 D;
      standard deviations [SD] D = 1.9 D; astigmatism < or =4.75 D), 87 hyperopic
      treatments (spherical equivalent < or =+4.25 D; average +2.4 D; SD = 0.9 D;
      astigmatism < or =3.5 D), and 14 treatments for mixed astigmatism (< or =4.5 D).
      Outcome data were obtained from a review of case notes and compared with
      historical data from FDA trials. MAIN OUTCOME MEASURES: Best-spectacle corrected
      visual acuity (BSCVA) preoperatively and at final review was compared in our case
      series with reference to the United Kingdom driving standard (BSCVA> or =20/30).
      Subsidiary outcome measures included duration of follow-up, intraoperative, and
      postoperative complication rates. Six-month postoperative data on standard safety
      criteria (numbers of patients losing > or =2 lines BSCVA, BSCVA <20/40, and final
      BSCVA <20/25 for patients with preoperative BSCVA > or =20/20) were examined in
      FDA trials. RESULTS: In our clinical series, no case with a preoperative BSCVA of
      20/20 or better had a final BSCVA of <20/30 at final review (97.5% confidence
      interval [CI], 0%-0.37%); 4 eyes had a BSCVA <20/25 (0.41%; 95%CI, 0.11%-1.02%).
      The median interval between surgery and final review was 2 months (range, 1-45
      months). In FDA studies recruiting pre-2000, 1.4% of patients lost > or =2 lines
      of BSCVA versus 0.6% in postmillennial studies (P = 0.005); 0.45% of patients in
      premillennial studies lost BSCVA to <20/40 compared with no patients in
      postmillennial studies (P = 0.001); and 1.68% of patients in premillennial
      studies with a preoperative BSCVA > or =20/20 had a postoperative BSCVA <20/25
      compared with 0.16% in postmillennial studies (P< or =0.001). CONCLUSIONS:
      Compared with premillennial results, the risk of visual loss is significantly
      reduced in contemporary LASIK.

PMID- 15953644
TI  - The dragged-fovea diplopia syndrome: clinical characteristics, diagnosis, and
      treatment.
AB  - PURPOSE: To identify the clinical characteristics of the dragged-fovea diplopia
      syndrome, to introduce a simple diagnostic test that aids in the evaluation of
      such patients, and to provide a simple treatment option to improve the diplopia
      in some of these patients. DESIGN: Retrospective, observational case series.
      PARTICIPANTS: Ninety-five affected eyes in 83 consecutive patients seen between
      January 1, 1993, and August 9, 2004, who were diagnosed with the dragged-fovea
      diplopia syndrome at one institution. METHODS: We reviewed the records of 222
      patients who have been seen in the Krieger Children's Eye Center at The Wilmer
      Institute since 1993 with a diagnosis of maculopathy, internal limiting membrane,
      or dragged fovea. We collected ocular findings and history for those patients who
      reported binocular diplopia that was not amenable to prism therapy and not
      secondary to acquired strabismus. MAIN OUTCOME MEASURES: We recorded the presence
      of metamorphopsia on Amsler grid testing or other clinical evidence of macular
      wrinkling, response to prism trial, response to the small-field central fusion
      test (lights on-off test), and response to partial occlusion with Scotch Satin
      tape (3M Co., St. Paul, MN). RESULTS: Ninety-five affected eyes in 83 patients
      met the criteria for inclusion in the study. All patients who were tested with
      the lights on-off test (n = 69) responded positively, demonstrating rapid central
      fusion with room lights off, and recurrence of central diplopia with peripheral
      fusion with room lights on. Forty-six patients (of 64 tested) were receptive to
      monocular occlusion with Scotch Satin tape. CONCLUSIONS: The dragged-fovea
      diplopia syndrome consists of central diplopia in the presence of peripheral
      fusion, secondary to dragging of the fovea in one or both eyes by retinal
      disease. The central diplopia cannot be eliminated by prism therapy or eye muscle
      surgery. The lights on-off test has proved pathognomonic for this syndrome, and
      many patients have benefited from partial monocular occlusion with Scotch Satin
      tape.

PMID- 15953645
TI  - Synthesis, solution equilibria and antiproliferative activity of copper(II)
      aminomethyltriazole and aminomethylthioxotriazoline complexes.
AB  - The aim of the present study was the synthesis, the determination of formation
      constants, and the evaluation of the antiproliferative activity of two copper(II)
      complexes formed with triazole-type ligands. The synthesis of the unsymmetrical
      triazole ligand 4-amino-3-aminomethyl-5-methyl-1,2,4-triazole (L1), and its
      copper(II) complex is reported. The ligand was prepared by functionalization of
      the carboxylate function of tert-butyloxycarbonyl (BOC) protected glycine O
      methyl ester. All intermediates and final products were isolated and
      characterized with IR, 1H NMR, and elemental analysis. X-ray structures of the
      ligand as a sulfate salt ((H2L1)2SO4.H2O) and the copper(II) complex
      [CuCl2(L1)(2)] are described. The ligand forms a (N,N) bidentate chelate with the
      amino group and one triazole nitrogen atom. The tetragonally distorted octahedral
      coordination of Cu(II) results from two axially coordinated chloride ions.
      Protonation constants for L1 and speciation of the Cu(II)/L1 system were
      determined in 0.1 M aqueous KCl solution at 25 degrees C. Complexes formed in
      solution were also characterized by visible spectrophotometry. Ligand
      substitution competition between L1 and glycine has also been studied using
      potentiometric titrations. Antiproliferative activities of ([CuCl2(L1)2]) and
      [CuCl2(H2L2)]Cl, where HL2 is the 5-thioxo analog of L1, against human tumor cell
      lines HT1080 and HT29 as well as normal human fibroblasts (HF) are presented
      along with the antiproliferative activities of L1, CuCl2, and cisplatin. Activity
      of these two complexes are discussed and compared with the activity of analogous
      compounds reported in the literature which contain pyridyl groups in place of the
      aminomethyl group. In particular, it is suggested that a lypophilic residue such
      as a pyridyl group is important for antiproliferative activity of this class of
      compounds.

PMID- 15953646
TI  - Crimean-Congo hemorrhagic fever in Eastern Turkey: clinical features, risk
      factors and efficacy of ribavirin therapy.
AB  - OBJECTIVES: This study described the clinical features, factors affecting the
      outcome of this disease, risk factors, and efficacy of ribavirin therapy for CCHF
      patients in Eastern Turkey. METHODS: Between 2002 and 2004, 60 cases admitted to
      our hospital were included in this study. The diagnosis was confirmed through
      detection of IgM by ELISA and/or genomic segment of virus by RT-PCR. RESULTS: In
      multivariate analysis, farming (OR, 11.4), living in a rural area (OR, 10.05) and
      being bitten by tick (OR, 6.75) were determined as risk factors for CCHF. The
      rates of fever during hospitalization, confusion, neck stiffness, bleeding from
      multiple sites, and presence of petechia/ecchymosis were higher in the patients
      who died than in surviving ones. Additionally, the mean values of ALT, AST, LHD,
      CK, PTT, INR and urea were also higher, and the mean PLT count was lower in the
      patients who died. Mean recovery time was shorter in the cases treated with
      ribavirin than those of control. But, the need for blood and blood product, mean
      hospitalization duration, fatality rates, and hospital expenditure values were
      not significantly different between the group of patients treated with ribavirin
      and control groups. CONCLUSIONS: In Eastern Turkey, clinical features, factors
      influencing outcome of the disease, and risk factors were similar to other
      outbreaks of CCHF. Further studies are needed for the evaluation of ribavirin
      therapy in CCHF.

PMID- 15953647
TI  - Apical expression of three RhopH1/Clag proteins as components of the Plasmodium
      falciparum RhopH complex.
AB  - The Plasmodium falciparum high molecular mass rhoptry protein ('PfRhopH') complex
      is important for parasite growth and comprises three distinct gene products:
      RhopH1, RhopH2 and RhopH3. We have previously shown that P. falciparum RhopH1 is
      encoded by either PFC0110w (clag3.2) or PFC0120w (clag3.1), members of the
      previously-named clag (cytoadherence-linked asexual gene) multigene family. In
      this report, we have further characterized rhoph1/clag members in terms of gene
      structure, transcription and protein expression. The cDNA sequences for all five
      rhoph1/clag members were determined, confirming previous in silico predictions of
      intron-exon boundaries. All member genes were transcribed in HB3 and 3D7 parasite
      lines, but clag3.2 was not transcribed in Dd2 parasites. The peak abundance of
      transcripts for all genes was observed during the late schizont stage. Antisera
      specific to Clag2 and Clag3.1 localized these proteins to the apical end of
      merozoites in segmented schizonts, and both proteins are found to be components
      of the PfRhopH complex. PfRhopH complex that was immunoprecipitated with anti
      Clag9 antibody contained neither Clag2 nor Clag3.1, thereby suggesting that
      PfRhopH complexes contain only individual rhoph1/clag gene products. Since the
      PfRhopH complex binds the erythrocyte surface, and RhopH2 and RhopH3 are encoded
      by single copy genes, the RhopH1/Clag proteins may serve to confer some degree of
      specificity to the roles of the individual complexes.

PMID- 15953648
TI  - Intracellular translocation of the decapeptide carboxyl terminal of Gi3 alpha
      induces the dual phosphorylation of p42/p44 MAP kinases.
AB  - The carboxyl terminal of heterotrimeric G protein alpha subunits binds both G
      protein-coupled receptors and mastoparan (MP), a tetradecapeptide allostere.
      Moreover, peptides corresponding to the carboxyl domains of G(i)3alpha and G(t)
      display intrinsic biological activities in cell-free systems. Thus, the purpose
      of this study was to develop a cell penetrant delivery system to further
      investigate the biological properties of a peptide mimetic of the G(i)3alpha
      carboxyl terminal (G(i)3alpha(346-355); H-KNNLKECGLY-NH2). Kinetic studies, using
      a CFDA-conjugated analogue of G(i)3alpha(346-355), confirmed the rapid and
      efficient intracellular translocation of TP10-G(i)3alpha(346-355) (t(0.5) = 3
      min). Translocated G(i)3alpha(346-355), but not other bioactive cargoes derived
      from PKC and the CB1 cannabinoid receptor, promoted the dual phosphorylation of
      p42/p44 MAPK without adverse changes in cellular viability. The relative
      specificity of this novel biological activity was further confirmed by the
      observation that translocated G(i)3alpha(346-355) did not influence the
      exocytosis of beta-hexoseaminidase from RBL-2H3, a secretory event stimulated by
      other cell penetrant peptide cargoes and MP. We conclude that TP10-G(i)3alpha(346
      355) is a valuable, non-toxic research tool with which to study and modulate
      signal transduction pathways mediated by heterotrimeric G proteins and MAPK.

PMID- 15953649
TI  - Estimating the probability of freedom of classical swine fever virus of the East
      Belgium wild-boar population.
AB  - A report of the Scientific Committee on Animal Health and Animal Welfare of the
      European Commission (CEC, 1999.) includes recommendations for setting up
      monitoring programmes for classical swine fever (CSF) infection in a wild-boar
      population, based on the assumption that one would detect at least 5% prevalence
      in a CSF-infected wild-boar population. This assumption, however, is not science
      based. We propose an alternative method to provide evidence for a wild-boar
      population being free of CSF and evaluate the efficiency of a surveillance
      programme that was implemented in Belgium in 1998. In our study, the probability
      of freedom of CSF-virus was estimated based on 789 samples; these were collected
      from wild-boars within the surveillance programme (within the three provinces
      which include 95% of the Belgian wild-boar population) and examined by three
      diagnostics methods (antibody detection, virus detection and virus RNA
      detection). A Bayesian framework was used for the estimation, accounting for the
      diagnostic test characteristics without the assumption of the presence of a gold
      standard. The median probability of freedom of CSF-virus was estimated at 0.970,
      with a 95% credibility interval of 0.149-1.000. Independent on the choice of the
      prior information, the posterior distributions for the probability of freedom of
      CSF-virus were always skewed close to the upper boundary of 1. This represents a
      big gain of knowledge since we did not use any prior information for the
      probability of freedom of CSF-virus and took the uncertainty about the accuracy
      of the diagnostic methods into account.

PMID- 15953650
TI  - Consumer acceptance of biotechnology and the role of second generation
      technologies in the USA and Europe.

PMID- 15953651
TI  - Re: Roberts, J.E., and Bell, M.A. 2003. Two- and three-dimensional mental
      rotation tasks lead to different parietal laterality for men and women.

PMID- 15953652
TI  - Postural control in otolith disorders.
AB  - It was the aim of the present paper to investigate the influence of otolith
      disorders on human postural control by different methods. The 33 patients of our
      study had undergone a minor head injury and suffered subsequently from an
      utricular or sacculo-utricular disorder as evidenced by vestibular evoked
      myogenic potential recordings and eccentric rotation recordings of the otolith
      ocular responses. Postural control was assessed by performing stance/gait tests
      (standard balance deficit test, SBDT) and by evaluating trunk sway (using angular
      velocity sensors). Moreover, classical tests of the posterior column of the
      spinal tract (Romberg/Unterberger) and the dynamic posturography (sensory
      organization test, SOT) were included. It could be shown that SBDT tasks with
      reduced proprioceptive and visual cues (e.g. standing on foam, eyes closed) are
      most sensitive for an otolith disorder. The patients showed an increased trunk
      sway in the pitch plane (i.e. linear motion as adequate utricular stimulus) and
      an increase in sway velocities (i.e. tilting movements as adequate saccular
      stimulus) compared to controls. The SOT was most sensitive for combined (sacculo
      utricular) otolith disorders (78%) while vestibulospinal tests are not enough
      sensitive. In essence, otolith disorders evidently impair human postural control
      and have been possibly underestimated as a source of posttraumatic postural
      imbalance as yet.

PMID- 15953653
TI  - New insights into regulation of the tryptophan biosynthetic operon in Gram
      positive bacteria.
AB  - The tryptophan operon of Bacillus subtilis serves as an excellent model for
      investigating transcription regulation in Gram-positive bacteria. In this
      article, we extend this knowledge by analyzing the predicted regulatory regions
      in the trp operons of other fully sequenced Gram-positive bacteria.
      Interestingly, it appears that in eight of the organisms examined, transcription
      of the trp operon appears to be regulated by tandem T-box elements. These
      regulatory elements have recently been described in the trp operons of two
      bacterial species. Single T-box elements are commonly found in Gram-positive
      bacteria in operons encoding aminoacyl tRNA synthetases and proteins performing
      other functions. Different regulatory mechanisms appear to be associated with
      variations of trp gene organization within the trp operon.

PMID- 15953655
TI  - Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms
      modulate the risk for migraine conferred by the MTHFR T677 allele.
AB  - There is growing evidence that folate metabolism is involved in migraine
      pathophysiology, mainly in migraine with aura. Even though folate metabolism is
      regulated by a number of enzymes, only two functional polymorphisms have been
      tested in association studies with migraine. Here, we have explored the possible
      role in migraine of other folate-metabolizing enzymes which are in close
      interdependency with 5',10'-methylenetetrahydrofolate reductase analyzing
      functional polymorphisms of these enzymes in a case-control study. Individually,
      thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase
      formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS)
      polymorphisms did not modify the general risk for suffering migraine.
      Nevertheless, we observed a strong interaction between TS and MTHFR mutated
      genotypes, which increased over 8-fold the risk for experiencing aura among
      migraineurs; MTHFD1 and MTHFR mutated genotypes also increased together the risk
      for migraine in general (OR = 3.08; 95% CI = 1.3-7.4). We conclude that the
      pathogenetic role of the MTHFR T677 allele in migraine is modulated by functional
      polymorphisms of TS and MTHFD1.

PMID- 15953654
TI  - Gene array profiling of large hypothalamic CNS regions in lactating and randomly
      cycling virgin mice.
AB  - A dramatic example of neuronal and physiological plasticity in adult mammals
      occurs during the transition from a non-maternal to a maternal, lactating state.
      In this study, we compared gene expression within a large continuous region of
      the CNS involved in maternal behaviors (hypothalamus, preoptic regions, and
      nucleus accumbens) between lactating (L) (postpartum Day 7) and randomly cycling
      virgin (V) outbred mice. Using high-density oligonucleotide arrays representing
      11,904 genes, two statistical algorithms were used to identify significant
      differences in gene expression: robust multiarray (P < 0.001) (n = 92 genes) and
      significance analysis of microarrays using a 10% false discover rate (n = 114
      genes). 27 common genes were identified as significant using both techniques. A
      subset of genes (n = 5) were selected and examined by real-time PCR. Our findings
      were consistent with previous published work. For example, neuropeptide Y (NPY)
      and proenkephalin were elevated in L mice, whereas POMC was decreased. Increased
      levels of NPY Y2 receptor and polo-like kinase and decreased levels of endothelin
      receptor type b in L mice are examples of novel gene expression changes not
      previously identified. Expression differences occurred in broad classes.
      Together, our findings provide possible new material on gene expression changes
      that may support maternal behaviors. The advantages and drawbacks of sampling
      large CNS regions using arrays are discussed.

PMID- 15953656
TI  - Visualizing forebrain-specific usage of an estrogen receptor alpha promoter for
      receptor downregulation in the rat.
AB  - Transgenic rats expressing enhanced green fluorescent protein (EGFP) under the
      control of an estrogen receptor (ER) alpha promoter were generated to tag ERalpha
      positive neurons in the brain. Two transgenes, one containing sequences for
      promoter A and DsRed and the other containing sequences for promoter 0/B and
      EGFP, were injected simultaneously into Wistar rat zygotes. Twenty-two founders
      with both transgenes were identified. Ten lines of these founders expressed the
      EGFP tag in the brains of their first filial generation, whereas none similarly
      expressed the DsRed tag. In two lines selected for the brightness of the EGFP
      fluorescence in their brains, tagged cells showed essentially the same patterns.
      Tagged cells were in the preoptic area (POA), bed nucleus of the stria terminalis
      (BNST), hypothalamic arcuate nucleus and medial amygdala. ERalpha-immunoreactive
      neurons were identified in all of these structures by immunohistochemistry. In
      ovariectomized females, approximately 75% of the EGFP-fluorescent cells in the
      POA-BNST were immunoreactive for ERalpha. In the POA-BNST, ovariectomy increased
      the number of EGFP-immunopositive cells and estrogen supplementation reversed
      this effect, indicating that the promoter 0/B is involved in estrogen-induced
      downregulation of ERalpha. EGFP was also present in cells in the cerebral cortex
      and hippocampus, which have not previously been associated with endocrine
      regulation. Conversely, only a few cells were tagged in the hypothalamic
      ventromedial nucleus, which contained many ERalpha-immunoreactive neurons. This
      discrepancy could have arisen as a result of differential promoter usage.

PMID- 15953657
TI  - Gender-specific association of insertion/deletion polymorphisms in the nogo gene
      and chronic schizophrenia.
AB  - Nogo is a myelin-associated protein associated with neurite outgrowth and
      regeneration. A previous study has reported an association between an
      insertion/deletion polymorphism in schizophrenia. We tested for the distribution
      of the polymorphism and haplotypes of this and another insertion/deletion
      polymorphism in our population. We have also developed an assay combining allele
      specific polymerase chain reaction (AS-PCR) and restriction fragment length
      polymorphism (RFLP) to simultaneously type these two insertion/deletion
      polymorphisms. There was a statistically significant difference at the allelic
      level for both the CAA (chi2 = 4.378, df = 1, P value = 0.036) and TATC (chi2 =
      5.807, df = 1, P = 0.016) polymorphisms in the female subgroup, but not in males.
      With our genotyping method, we also determined the molecular haplotype. Within
      the female gender, odds ratio is at 1.57 (95% CI 1.05-2.37) for CAACAA-TATC and
      1.40 (95% CI 0.55-3.60) for CAA-TATC, the two at-risk haplotypes. Odds ratio is
      0.63 (95% CI 0.42-0.93) for the protective wildtype haplotype CAA-TATCTATC.
      Further study of these two polymorphisms to investigate functional significance
      and confirm gender-specific association should be carried out.

PMID- 15953658
TI  - Toxicity data in addition to survival data are important in evaluating the
      applicability of a chemotherapy regimen of advanced non-small-cell lung cancer.

PMID- 15953659
TI  - Homeostatic alterations induced by interleukin-1beta microinjection into the
      orbitofrontal cortex in the rat.
AB  - The present experiments were designed to elucidate the effect of direct
      orbitofrontal cortical administration of interleukin-1beta (IL-1beta) on the
      homeostatic regulation. Short- and long-term food intakes (FI), water intakes and
      body temperature (BT) were measured before and after a bilateral microinjection
      of IL-1beta (with or without paracetamol /P/ pretreatment) into the orbitofrontal
      cortex (OBF) of Wistar rats, and the effects were compared with those found in
      vehicle-treated and i.p. injected IL-1beta, IL-1beta+P or control animals. In
      addition, blood glucose levels (BGLs), along a glucose tolerance test, and plasma
      concentrations of insulin, leptin, cholesterol, triglycerides and urate were
      determined in cytokine treated and control rats. Short-term FI was suppressed
      after orbitofrontal cortical or peripheral application of IL-1beta. In the long
      term FI, however, there was no significant difference among the groups. Cytokine
      microinjection into the OBF, similar to the i.p. administration, was also
      followed by a significant increase in BT. Pretreatment with P failed to influence
      the anorexigenic and hyperthermic effects of the centrally administered IL-1beta.
      The sugar load led to a diabetes-like prolonged elevation of BGL in the IL-1beta
      treated animals. Following cytokine administration, plasma levels of insulin and
      that of triglycerides were found decreased, whereas that of uric acid increased.
      The present findings confirm that the OBF is one of the neural routes through
      which IL-1beta exerts modulatory effect on the central homeostatic regulation.

PMID- 15953660
TI  - A case-control study of risk factors associated with rectal colonization of
      extended-spectrum beta-lactamase producing Klebsiella sp. in newborn infants.
AB  - To determine the risk factors for rectal colonization by extended-spectrum beta
      lactamase (ESBL) Klebsiella sp. in 368 newborns admitted consecutively to a
      neonatal intensive care unit over six months, rectal swabs were cultured on
      admission and weekly until discharge. Eighty infants (21.7%) had ESBL Klebsiella
      sp. cultured from their rectal swabs. Eighty controls were selected at random
      from infants with negative cultures admitted within the 14-day period prior to
      the detection of ESBL Klebsiella sp. in the cases. Cases had significantly lower
      birth weight, gestational age, earlier age of admission, longer hospital stay,
      and higher proportions of congenital malformations, early-onset pneumonia and
      respiratory distress syndrome compared with controls. Significantly more cases
      received mechanical ventilation, nasal continuous positive airway pressure
      support, total parenteral nutrition, umbilical vascular catheterization, arterial
      line insertion, urinary bladder catheterization, and prior treatment with
      antibiotics. However, stepwise logistic regression analysis showed that only two
      independent risk factors were significantly associated with ESBL rectal
      colonization: duration of hospital stay [adjusted odds ratio (OR): 1.3; 95%
      confidence intervals (CI): 1.2, 1.4; P<0.0001) and early-onset pneumonia
      (adjusted OR: 8.3; 95% CI: 1.6, 43.4; P=0.01).

PMID- 15953661
TI  - Lifelong corticosterone level determines age-related decline in neurogenesis and
      memory.
AB  - Ageing is accompanied by an alteration of spatial memory, a decline in
      hippocampal neurogenesis and a dysregulation of the hypothalamic-pituitary axis
      (HPA) leading to elevated levels of circulating corticosterone. However, the role
      of the HPA axis in age-related decline in cognitive functions and in neurogenesis
      decline remains unclear. We found that suppression of glucocorticoids secretion
      from midlife to the rest of the animals' life increases neurogenesis in old
      animals and prevents the emergence of age-related memory disorders. Reciprocally,
      aged rats with a chronic upregulation of the HPA axis exhibit not only spatial
      memory impairments but also very low levels of hippocampal cell proliferation and
      survival. Altogether, these results indicate that the extent of lifetime exposure
      to glucocorticoids determines the extent of age-related decline in hippocampal
      neurogenesis and consequently age-related cognitive dysfunctions.

PMID- 15953662
TI  - [Anaerobic deep abscesses with unusual location: report of 5 cases].
AB  - OBJECTIVE: Anaerobic deep abscesses are rare and may have unusual location
      leading to severe outcome due to delayed diagnosis and treatment. In order to
      improve their diagnosis, we report and analyse 5 new cases. METHODS: Patients
      were seen from 1999 to 2003 in a single department of internal medicine of the
      university hospital of Marseille. RESULTS: Five new cases were diagnosed
      consisting in 3 females and 2 males with a medium age of 56,8 years, with unusual
      location in 4 cases: epidural (2), psoas (1) and sub-diaphragmatic (1) or
      circumstances in one case of pulmonary abscess unrelated to inhalation.
      Predisposing conditions thought to compromise resistance to infection were found
      in all cases: social poverty (4/5), alcoholism (3/5), smoking (4/5), teeth and
      periodontal disease (4/5), neoplasia (2/5), iatrogenic disease (2/5). Symptoms
      were insidious (5/5) and unspecific but were always related to the abscess
      location. Abscesses were frequently found distant from the initial focus of
      infection because of frequent hematogenous spread (4/5). Drainage of the
      collection led to bacterial identification in all cases (4/4), although blood
      cultures could be positive (3/5) and helpful in one case in which drainage was
      not possible (1/5). The isolated organisms always corresponded to the suspected
      initial focus (oropharynx 4/5 and digestive 1/5). Finally, combination of
      surgical drainage and double prolonged antibiotherapy (penicillin+metronidazole)
      was the elected treatment. CONCLUSION: Since hematogenous diffusion is frequent,
      anaerobic infection should be suspected in any case of deep abscess affecting
      patients with predisposing conditions such as poverty, severe teeth disease or
      iatrogenic procedure.

PMID- 15953663
TI  - [Horton's disease revealed by brachial C5 plexopathy].
AB  - BACKGROUND: Shoulder palsy due to brachial plexopathy (or lower cervical
      radiculopathy) is a rare occurrence in patients with giant cell temporal
      arteritis (TA). We report a patient with C5 plexopathy revealing TA, with review
      of the literature. EXEGESIS: A 67-year-old woman presented with a complex
      neurological syndrome of rapid onset, including a left trigeminal neuralgia,
      painless masticatory palsy, impaired swallowing, and severe palsy of the left
      shoulder, corresponding to a C5 plexitis. Giant cell arteritis was suspected on
      clinical and laboratory grounds and was documented on temporal artery biopsy.
      Treatment with pulse methylprednisolone (100 mg every 8 hours for three days),
      followed by prednisone (1 mg/kg daily), resulted in progressive improvement of
      the neurological deficits, full shoulder strength being recovered within 6
      months. An extensive world literature allowed us to review 23 other cases of TA
      complicated by either lower cervical radiculopathy or C5 brachial plexopathy.
      These peripheral neuropathic manifestations occurred sometimes bilaterally and
      were isolated or, less often, part of a mononeuritis multiplex. Involved patients
      were relatively young (mean age 67 years) and 54% were men. The pathophysiology
      of TA-associated C5 radiculopathy or brachial plexitis is still poorly
      understood. Fortunately, functional prognosis was consistently good with
      corticosteroid treatment. CONCLUSION: Giant cell arteritis should always be
      considered in elderly or middle-aged patients presenting with C5 radiculopathy or
      plexopathy and elevated inflammatory markers.

PMID- 15953664
TI  - [Legionellosis mimicking adult onset Still's disease].

PMID- 15953665
TI  - A unique case of total foot-to-hand transfer in an infant with monodactyly.
AB  - A unique case of total foot-to-hand transfer, including the calcaneus, in an 8
      month-old infant with monodactyly is described. Several technical and
      psychological aspects of the case are also discussed.

PMID- 15953666
TI  - Adolescents, substance abuse, and the treatment of insomnia and daytime
      sleepiness.
AB  - Adolescence is a time of change that can be both exciting and stressful. In this
      review, we focus on the central role that disturbed sleep and daytime sleepiness
      occupies in interactions involving substance abuse and negative health, social,
      and emotional outcomes. As a means of improving sleep and lowering risk for
      recidivism of substance abuse, we developed and implemented a six-session group
      treatment to treat sleep disturbances in adolescents who have received treatment
      for substance abuse. The components of the treatment are stimulus control
      instructions, use of bright light to regularize sleep, sleep hygiene education,
      cognitive therapy, and Mindfulness-Based Stress Reduction. Preliminary evidence
      indicates that participants who completed four or more sessions in the treatment
      program showed improved sleep and that improving sleep may lead to a reduction in
      substance abuse problems at the 12-month follow-up.

PMID- 15953667
TI  - Physician migration: views from professionals in Colombia, Nigeria, India,
      Pakistan and the Philippines.
AB  - There has been much debate recently about several issues related to the migration
      of physicians from developing to developed countries. However, few studies have
      been conducted to address these issues in a systematic fashion. In an attempt to
      begin the process of generating systematic data, we designed and distributed a
      questionnaire addressing several core issues surrounding physician migration to
      respondents selected on the basis of their special expertise or experience in
      India, Nigeria, Pakistan, Colombia, and the Philippines. The issues addressed
      relate to the reasons physicians migrate to developed countries, how migration is
      related to the structure of medical education, the effect that migration has on
      the health care infrastructure of developing countries, and various policy
      options for dealing with physician migration. Though responses varied somewhat by
      country, a desire for increased income, greater access to enhanced technology, an
      atmosphere of general security and stability, and improved prospects for one's
      children were the primary motivating factors for physician migration. A majority
      of respondents believed that physicians in developing counties are provided with
      highly specialized skills that they can better utilize in developed countries,
      but respondents were ambivalent with respect to the utility of educational
      reform. Responses varied significantly by country with regard to whether
      physician migration results in physician shortages, but there was widespread
      agreement that it exacerbates shortages in rural and public settings. With
      respect to policy options, increasing physician income, improving working
      conditions, requiring physicians to work in their home countries for a period
      following graduation from medical school, and creating increased collaboration
      between health ministries in developed and developing countries found the most
      favor with respondents.

PMID- 15953668
TI  - Barriers to cervical cancer screening: a qualitative study with women in Serbia.
AB  - Serbia employs opportunistic approaches to cervical cancer screening, leading to
      inequitable health care access. To better understand the health care needs of
      women, we investigated their knowledge of and perceived barriers to cervical
      cancer screening. Data reported in the paper arise from nine focus group
      discussions with 62 women from diverse socio-economic backgrounds. They were
      recruited in two cities with contrasting social settings, Belgrade, the Serbian
      capital, and a regional town, Smederevo. Thematic analysis identified that the
      interplay of social and personal barriers influenced women's poor presentation
      for screening. Inadequate public health education, lack of patient-friendly
      health services, socio-cultural health beliefs, gender roles, and personal
      difficulties were the most salient barriers to screening. We suggest how within
      the context of opportunistic screening patient education may be employed. The
      introduction of compulsory cervical cancer screening, suggested by some
      participants, is also discussed.

PMID- 15953669
TI  - "Unless you went in with your head under your arm": patient perceptions of
      emergency room visits.
AB  - There is increasing concern in Canada regarding growing pressures on emergency
      room care. Frequent media reports call attention to overcrowding, lengthy waiting
      times and the re-routing of ambulances due to the closure of emergency rooms
      during periods of overcrowding. Much of this information, however, is anecdotal.
      As such, little is known about patients' experiences in emergency rooms in
      Canada. The purpose of this study is to explore patients' perceptions of their
      most recent emergency room visit. Semi-structured, in-depth interviews were
      conducted with 41 men and women from two socially distinct neighbourhoods in
      Hamilton, Ontario, Canada. Much of the previous work on experiences in emergency
      room care is international in scope and uses quantitative methods to examine
      patient satisfaction with emergency care. This study considers patient
      experiences more broadly and looks beyond satisfaction to examine reasons for
      seeking emergency room care and the factors that shape experiences. The findings
      show that most patients describe their experiences in negative terms. The aspects
      of emergency room care that were most often linked with negative experiences were
      waiting times, patient perceptions of the quality of care received and staff
      patient interactions. The findings are discussed in the context of recent health
      care reforms in Canada, which we argue have not addressed adequately the 'crisis'
      in emergency rooms.

PMID- 15953670
TI  - Psychiatrists as social engineers: a study of an anti-stigma campaign.
AB  - Anti-stigma campaigns in the field of mental health appeared in a variety of
      countries and organizations during the 1990s. This paper examines one of these-
      the 'Changing Minds' Campaign of the Royal College of Psychiatrists in Britain.
      The paper aims to elucidate the role the campaign played in the professional
      project of psychiatry and situate it in a wider context of both sociology and
      changes in mental health policy. The interest work involved is set in the context
      of the long-standing controversies surrounding psychiatric theory and practice,
      as well as the network of other agencies and actors seeking improvements in the
      citizenship of people with mental health problems in a post-institutional world.

PMID- 15953671
TI  - The role of 5-HT2C receptor polymorphisms in the pharmacogenetics of
      antipsychotic drug treatment.
AB  - The development of novel, atypical antipsychotics has been welcomed due to their
      lower incidence of extrapyramidal side effects. However, as with all
      pharmacotherapy, patient response is often varied and these novel compounds are
      not without their own side effect profile, most notably weight gain. Inter
      individual variations in response to drug treatment are, in part, due to
      polymorphisms of the genes encoding drug targets. The importance of the serotonin
      system in psychiatric symptomatology and several side effects of antipsychotic
      drugs is well established. Thus genetic polymorphisms of two central 5-HT
      receptors (5-HT2A and 2C), at which many of the newer antipsychotic drugs act,
      are prime candidates for pharmacogenetic analysis of the effects of these drugs
      in the treatment of schizophrenia. To date, much work has focussed on the 5-HT2A
      receptor subtype. However, pharmacological evidence and recent molecular genetic
      studies would suggest a role for the 5-HT2C receptor in the consequences of
      antipsychotic treatment, particularly in relation to the development of both drug
      induced dyskinesias and weight gain. This review briefly examines the
      pharmacology and physiology of the 5HT2C receptor in the context of its genetics,
      with discussion of known polymorphisms of this receptor gene and its promoter
      region. Associations between these polymorphisms and the development of
      schizophrenia, the symptom responses to antipsychotic treatment and side effects
      of such treatment, notably tardive dyskinesia and weight gain, are assessed and
      related to the presumed functionality of these polymorphisms. Such studies
      clearly demonstrate the potential of pharmacogenetics in optimising treatment for
      the individual patient.

PMID- 15953672
TI  - Effects of a low dose of bentazon on spermatogenesis of mice exposed during
      foetal, postnatal and adult life.
AB  - Bentazon is a herbicide used to control many broadleaf weeds and sedges. Its use
      has improved rice production in paddy fields in Northern Italy, but as a negative
      consequence it is found in groundwater, the major source of drinking water. To
      determine whether low doses of bentazon affect spermatogenesis, it was dissolved
      in water at the concentration of 30 microg/L. Bentazon was administered through
      drinking water to: (1) adult mice for 100 days and (2) mice exposed in utero,
      during lactation and for 100 days after birth. The histopathological analysis of
      testes of treated animals showed that the frequency of defective tubules was
      comparable to that found in control groups. The cell associations of the 12
      stages of the seminiferous epithelium were correct as well as the architecture of
      the epithelium. The spermatocytes/spermatids ratio was the same as in controls.
      However, the frequency of stages VII, IX and XII of the cycle of the seminiferous
      epithelium of adult mice and of stages I, III and VII of mice exposed in utero
      and for 100 days after birth was different when compared to that of control mice.
      Sperm number and morphology were not affected by the treatment. The potential
      genotoxic effects were evaluated on spermatozoa (Comet assay), in pachytene
      spermatocytes (analysis of the synaptonemal complex) and in bone marrow cells
      (frequency of micronuclei). None of these analyses evidenced genotoxic effects of
      bentazon. Although our results show that the administration of a low dose of
      bentazon does not impair spermatogenesis, we found alterations of the frequency
      of some stages of the cycle of the seminiferous epithelium in both experimental
      groups.

PMID- 15953673
TI  - Interleukin-1beta (IL-1beta) induces a crosstalk between cAMP and ceramide
      signaling pathways in thyroid epithelial cells.
AB  - Interleukin-1 beta (IL-1beta) is an important regulator of the thyroid cell
      function. This cytokine has been largely described to trigger an important
      biological signaling cascade: the sphingomyelin/ceramide pathway. In this report,
      we show that IL-1beta induces the transient activation of a neutral
      sphingomyelinase in porcine thyroid cells. Moreover, IL-1beta and ceramides are
      demonstrated to inhibit the TSH-induced cAMP production via the implication of
      alphaGi subunit of the adenylyl cyclase system. This crosstalk between cAMP and
      ceramide pathways constitutes a preponderant process in the TSH-controlled
      differentiation state of thyrocytes. All these results argue for the involvement
      of ceramides and IL-1beta in the thyroid function regulation, leading to a cell
      dedifferentiated state.

PMID- 15953674
TI  - The V2 segment of the vertebral artery in anterior and anterolateral cervical
      spinal surgery: a cadaver angiographic study.
AB  - OBJECTIVE: The second segment of the vertebral artery is under the risk of injury
      during anterior and anterolateral cervical spine procedures. To avoid such a
      risk, one needs to be familiar with the regional anatomy. The aim of this study
      was to measure the distance between the vertebral artery and the uncinate
      process, midline, and the medial side of the longus colli muscle using vertebral
      artery angiograms at the level of C6, C5, C4, and C3 vertebrae. MATERIALS AND
      METHODS: In 12 human cadavers, the vertebral arteries were first irrigated with
      water. Then the arteries were filled with silicon and barium, and finally their
      angiographic images were obtained. RESULTS: The transverse diameter of the
      vertebral artery was measured at C6, C5, C4, C3, and C2 level. The values on the
      left were bigger than the values on the right (p>0.05). The distance between the
      vertebral artery and the midline decreased from C6 (17.2+/-5.6mm on the right,
      17.2+/-2.3mm on the left) to C3 (15.8+/-5.3mm on the right, 13.8+/-2.1mm on the
      left) (p>0.05). The distance between the apex of the uncinate process and the
      medial side of the vertebral artery was found to be longer at C4 (2.7+/-1.0 mm on
      the right, 2.2+/-1.0mm on the left) and C5 (2.5+/-1.1mm on the right, 2.5+/-1.0mm
      on the left) vertebra levels on the right side (p=0.339 at C4, p=0.862 at C5).
      The distance between the medial side of the longus colli muscle and the medial
      side of the vertebral artery was measured as 9.7+/-2.7 mm (9.5+/-2.9 mm on the
      right, 9.8+/-2.6mm on the left) at C6 level, 9.2+/-2.6mm (8.6+/-2.4mm on the
      right, 9.8+/-3.1mm on the left) at C5, 9.4+/-1.9 mm (9.2+/-2.1mm on the right,
      9.5+/-2.0mm on the left) at C4, and 10.4+/-2.7 mm (10.5+/-3.0mm on the right,
      10.1+/-2.6mm on the left) at C3 vertebra level. No significant difference was
      found between the right and the left (p>0.05). The angle between the vertebral
      artery and the midline was measured as 4.0+/-1.9 degrees on the right and 2.2+/
      1.4 degrees on the left side (p=0.030). CONCLUSION: It was considered that the
      values obtained could be useful in anterolateral and anterior cervical approaches
      in terms of evaluating the position of the vertebral artery and its relation to
      vertebral structures. It is also concluded that the risk of injury in upper
      subaxial cervical spine is higher than in the lower part of the subaxial cervical
      spine.

PMID- 15953675
TI  - Suppression of pancreatic tumor progression by systemic delivery of a pancreatic
      cancer-specific promoter driven Bik mutant.
AB  - Pancreatic cancer is highly aggressive with extremely poor prognosis. Developing
      a pancreatic cancer specific promoter (PCSP) is one approach for pancreatic
      cancer gene therapy. We have modified the promoter of cholecystokinin type A
      receptor (CCKAR), named CCK/Mpd, which possesses a relatively high activity in
      pancreatic cancer cells as compared with normal cells. The CCK/Mpd promoter
      driven luciferase exhibits a better tumor specific tissue distribution than the
      CMV promoter-driven luciferase when systemically administered in vivo. Notably,
      we demonstrate a treatment efficacy by using CCK/Mpd-Bik-DD/liposome in a nude
      mice xenograft model, suggesting the feasibility of PCSP-based gene therapy in
      pancreatic cancer treatment.

PMID- 15953676
TI  - Fractalkine gene therapy for neuroblastoma is more effective in combination with
      targeted IL-2.
AB  - The induction of tumor protective immunity against neuroblastoma remains a major
      challenge for active immunotherapy. Fractalkine is a unique Th1 CX3C chemokine
      known to induce adhesion and migration of leukocytes mediated by both, a membrane
      bound and soluble form, respectively. Here, we tested the hypothesis that
      chemokine gene therapy with fractalkine (FKN) induces an effective anti
      neuroblastoma immune response amplified by targeted IL-2 using the anti-GD2
      antibody ch14.18 fused with IL-2 (ch14.18-IL-2). For this purpose, NXS2 cells
      were genetically engineered to stably produce murine FKN (NXS2-FKN).
      Transcription and expression of the mFKN gene in tumor tissue of mice inoculated
      with NXS2-FKN cells were demonstrated in vivo. Importantly, mFKN exhibited a
      reduction in primary tumor growth and spontaneous liver metastases in syngenic
      A/J mice. This effect was boosted by targeted IL-2 using small non-curative doses
      of ch14-18-IL-2. The amplification of the FKN induced immune response was
      specific, since a non-specific antibody-IL-2 fusion protein ch225-IL-2 was
      ineffective. In summary, we demonstrated for the first time that chemokine gene
      therapy is amplified by targeted IL-2 suggesting a combination of both strategies
      as an adjuvant therapy for neuroblastoma.

PMID- 15953677
TI  - Isolation and characterization of a scFv antibody specific for tumor endothelial
      marker 1 (TEM1), a new reagent for targeted tumor therapy.
AB  - Tumor endothelial marker 1 (TEM1) is a protein predominantly expressed on the
      cell surface of endothelial cells in newly developing blood vessels and on tumor
      cells. It is therefore ideally suited as a target for anti-angiogenic tumor
      therapy. Using phage display technology a single chain antibody fragment (scFv
      CM6) was isolated that specifically binds to the extracellular part of TEM1.
      Antibody specificity was determined in ELISA, by Western analysis, fluorescence
      microscopy and flow cytometry performed with TEM1-expressing cells. ScFv-CM6 was
      further functionalized and coupled to liposomes. Such immunoliposomes loaded with
      the cytotoxic drug N4-octadecyl-1-beta-D-arabinofuranosylcytosine-(5'-5')-3'-C
      ethinylcytidine showed increased binding affinity and up to 80% higher cytotoxic
      activity towards TEM1-expressing IMR-32 tumor cells compared with control
      liposomes.

PMID- 15953678
TI  - Systemic administration of propentofylline does not attenuate morphine tolerance
      in non-injured rodents.
AB  - Propentofylline is a phosphodiesterase inhibitor that has been shown to attenuate
      the onset of morphine tolerance when administered intrathecally to rats. The
      present studies examined whether systemic administration could be effective in
      attenuating morphine tolerance in non-injured rodents using a similar dosing
      paradigm. Propentofylline at 10, 30, or 50 mg/kg, administered intraperitoneally
      once daily for 5 days, was unable to attenuate morphine tolerance established by
      twice daily administration of 10 mg/kg morphine. These results suggest that
      direct delivery of propentofylline to the central nervous system (CNS) may be
      required in order to attenuate morphine tolerance.

PMID- 15953679
TI  - Low molecular weight polyethylenimine for efficient transfection of human
      hematopoietic and umbilical cord blood-derived CD34+ cells.
AB  - With the emerging role of hematopoietic stem cells as potential gene and cell
      therapy vehicles, there is an increasing need for safe and effective nonviral
      gene delivery systems. Here, we report that gene transfer and transfection
      efficiency in human hematopoietic and cord blood CD34+ cells can be enhanced by
      the use of low molecular weight polyethylenimine (PEI). PEIs of various molecular
      weights (800-750,000) were tested, and our results showed that the uptake of
      plasmid DNA by hematopoietic TF-1 cells depended on the molecular weights and the
      N/P ratios. Treatment with PEI 2K (m.w. 2000) at an N/P ratio of 80/1 was most
      effective, increasing the uptake of plasmid DNA in TF-1 cells by 23-fold relative
      to Lipofectamine 2000. PEI 2K-enhanced transfection was similarly observed in
      hematopoietic K562, murine Sca-1+, and human cord blood CD34+ cells. Notably, in
      human CD34+ cells, a model gene transferred with PEI 2K showed 21,043- and 513
      fold higher mRNA expression levels relative to the same construct transfected
      without PEI or with PEI 25 K, respectively. Moreover, PEI 2K-treated TF-1 and
      human CD34+ cells retained good viability. Collectively, these results indicate
      that PEI 2K at the optimal N/P ratio might be used to safely enhance gene
      delivery and transfection of hematopoietic and human CD34+ stem cells.

PMID- 15953680
TI  - Effect of pressure on pulse radiolysis reduction of proteins.
AB  - Pulse radiolysis experiments were performed on proteins under pressure. Whereas
      many spectroscopic techniques have shown protein modifications at different
      pressure ranges, the present measurements performed using the water radiolysis
      allowed to generate radical species and to study the mechanisms implied in their
      reactions with proteins. This work gives the first results obtained on the
      effects of pressure on the rate constants of the proteins reduction by the
      hydrated electron at pressures up to 100 MPa. The reaction with the hydrated
      electron was investigated on two classes of protein: the horse myoglobin and the
      mussel metallothioneins. We have successively studied the influence of the pH
      value of metmyoglobin solutions (pH 6, 7 and 8) and the influence of the metals
      nature (Zn,Cu,Cd) bound to metallothioneins. For both protein, whatever the
      experimental conditions, the pressure does not influence the value of the
      reduction rate constant in the investigated range (0.1-100 MPa).

PMID- 15953681
TI  - Clinical study of a formula for delayed rapid fluid resuscitation for patients
      with burn shock.
AB  - OBJECTIVE: To explore a suitable formula of delayed rapid fluid resuscitation for
      patients with burn shock. METHODS: Twenty patients with burns over 40% of total
      body surface area (TBSA) admitted 4-8 h after injury were studied. Plasma was
      used as colloid in 9 cases in the infused patients (the plasma group, PG) and
      gelofusine was used as colloid in 11 cases in the infused patients (the
      gelofusine group, GG). Rapid fluid resuscitation was administered under strict
      hemodynamic monitoring immediately after admission. Hemodynamic indexes including
      pulmonary arterial pressure (PAP), pulmonary artery wedge pressure (PAWP),
      cardiac output (CO), pulmonary vascular resistance (PVR), and systemic vascular
      resistance (SVR), hemorheological parameters such as blood viscosity and plasma
      viscosity, and tissue oxygenation indices oxygen delivery (DO2), oxygen
      consumption (VO2), oxygen extraction (O2ext), lactic acid (LA) and base
      deficiency of arterial blood (AD) were determined in order to monitor function in
      or damage to important viscera. RESULTS: The amount of fluid rapidly infused in
      the first 2 h after hospitalization accounted for 38.8+/-6.0% of the required
      fluid amount for the first 24 h as calculated from the formula. When the amount
      of fluid infused into the patient before admission to our hospital was added, the
      total amount accounted for 48.3+/-5.0% of the fluid amount for the first 24 h.
      The actual amount of fluid infused in the first 24 h was 31.4+/-8.9% more than
      that of the amount calculated with the Evans' formula. The amount of fluid
      infused in the second 24 h was nearly equal to the amount calculated with the
      Evans' formula. After fast fluid replacement therapy, all the parameters
      determined were markedly improved. CONCLUSION: It is suggested on the basis of
      our study that the fluid amount for delayed rapid fluid resuscitation in patients
      with burn shock should be calculated as follows: (1) in the first 24h, the amount
      of fluid (ml) is equal to TBSA (%) x body weight (kg) x 2.6. The ratio between
      colloid and electrolytes is 1:1, each of the two fluid types is 1.3 ml per (%)
      TBSA per kg body weight. The volume of water required is 2000 ml. Half of the
      total amount of fluid is proposed should be infused in the first 2 h after
      hospitalization under strict monitoring of hemodynamic indices. (2) In the second
      24 h, the amount of fluid (ml) is equal to TBSA (%) x body weight (kg) x 1. The
      ratio between colloid and electrolytes 1:1, each of the two is 0.5 ml. Water
      volume is 2000 ml.

PMID- 15953682
TI  - The central termination of sensory fibers from nerves to the gastrocnemius muscle
      of the rat.
AB  - Peripheral nerves innervating muscles have sensory fibers that relay information
      into the CNS information about proprioception, pain, and the metabolic state of
      the muscle. The present study shows the primary afferent projections into the
      spinal cord of the nerves innervating the gastrocnemius muscle of the rat using
      the transganglionic transport of a cocktail of horseradish peroxidase (HRP)
      conjugated to cholera toxin and wheat germ agglutinin; these markers have been
      shown to label large and small fibers, respectively. A dense projection into
      lamina I of the lumbar dorsal horn and a more moderate projection into lamina V
      were seen. Moreover, dense reaction product was found in the most medial aspect
      of lamina II, especially lamina II inner part, and less in lamina III and IV of
      levels L3-L5. Lamina VI had dense reaction product from the rostral sacral levels
      of the spinal cord that continued into Clarke's column at rostral lumbar levels.
      The nucleus gracilis also was labeled. Other nerves emerging from the popliteal
      fossa, including the tibial, peroneal, and sural nerves, also were injected with
      the HRP cocktail and their projections compared with those from the gastrocnemius
      muscle. Projections from the gastrocnemius muscle only partially overlapped with
      those from the tibial nerve, from which the nerves to the gastrocnemius muscle
      branch. However, the topology of projections from these nerves to laminae II-IV
      of the dorsal horn differed from that of the nerves of the gastrocnemius muscle,
      suggesting there was little spread to other nerves in the popliteal fossa. It was
      also noted that large labeled processes, presumably dendrites of retrogradely
      labeled motoneurons, entered the dorsal horn. These data provide information on
      the central projections of both the large and small fibers innervating the
      gastrocnemius muscle, and may aid in determining the circuitry utilized in the
      exercise pressor reflex as well as muscle pain.

PMID- 15953683
TI  - Cannabinoid-receptor 1 null mice are susceptible to neurofilament damage and
      caspase 3 activation.
AB  - Administered cannabinoids have been shown to ameliorate signs of CNS inflammatory
      disease in a number of animal models, including allergic encephalomyelitis. More
      recently, neuroprotective actions have been attributed to activation of the
      cannabinoid 1 receptor in a number of in vitro and in vivo models. One of these,
      chronic relapsing experimental allergic encephalomyelitis, is considered a robust
      analog of multiple sclerosis. In this study, spinal cord tissue from cannabinoid
      receptor 1 knockout mice was analyzed for neurofilament H and myelin basic
      protein content, as markers of neurons/axons and myelin respectively, during the
      course of chronic relapsing experimental allergic encephalomyelitis.
      Dephosphorylation of a neurofilament H epitope, immunoreactive to the SMI32
      antibody, was assessed as a marker of axonal damage and levels of the endpoint
      cell death mediator caspase 3 were evaluated. It was found that both
      neurofilament and myelin basic protein levels decrease over the course of
      disease, indicating concomitant neuronal/axonal loss and demyelination. Loss of
      each marker was more severe in cannabinoid receptor 1 knockout animals. Increased
      SMI32 reactivity was observed as disease progressed. SMI32 reactivity was
      significantly increased in knockout animals over wildtype counterparts, an
      indication of greater axonal dephosphorylation and injury. Active caspase 3
      levels were increased in all animals during disease, with knockout animals
      displaying highest levels, even in knockout animals prior to disease induction.
      These results indicate that lack of the cannabinoid receptor 1 is associated with
      increased caspase activation and greater loss and/or compromise of myelin and
      axonal/neuronal proteins. The increase of caspase 3 in knockout mice prior to
      disease induction indicates a latent physiological effect of the missing
      receptor. The data presented further strengthen the hypothesis of neuroprotection
      elicited via cannabinoid receptor 1 signaling.

PMID- 15953685
TI  - In cat four times as many lamina I neurons project to the parabrachial nuclei and
      twice as many to the periaqueductal gray as to the thalamus.
AB  - The spinothalamic tract, and especially its fibers originating in lamina I, is
      the best known pathway for transmission of nociceptive information. On the other
      hand, different studies have suggested that more lamina I cells project to the
      parabrachial nuclei (PBN) and periaqueductal gray (PAG) than to the thalamus. The
      exact ratio of the number of lamina I projections to PBN, PAG and thalamus is not
      known, because comprehensive studies examining these three projections from all
      spinal segments, using the same tracers and counting methods, do not exist. In
      the present study, the differences in number and distribution of retrogradely
      labeled lamina I cells in each segment of the cat spinal cord (C1-Coc2) were
      determined after large wheat germ agglutinin-conjugated horseradish peroxidase
      (WGA-HRP) injections in either PBN, PAG or thalamus. We estimate that
      approximately 6000 lamina I cells project to PBN, 3000 to PAG and less than 1500
      to the thalamus. Of the lamina I cells projecting to thalamus or PAG more than
      80%, and of the lamina I-PBN cells approximately 60%, were located on the
      contralateral side. In all cases, most labeled lamina I cells were found in the
      upper two cervical segments and in the cervical and lumbar enlargements.

PMID- 15953684
TI  - The effect of GIRK2(wv) on neurite growth, protein expression, and viability in
      the CNS-derived neuronal cell line, CATH.A-differentiated.
AB  - Death occurs in the homozygous mutant mouse weaver among several classes of
      neuron in cerebellum and ventral midbrain, because these neurons carry a mutation
      in the G protein-gated inwardly rectifying potassium channel, Girk2. GIRK2 is
      expressed in all neuronal types killed by wv in cerebellum and midbrain as well
      as in neurons elsewhere that suffer lesser consequences. GIRK2(wv) affects
      neurons postnatally, after proliferation, at the time of final differentiation.
      To assess the impact of GIRK2(wv) on neuronal development and viability, we
      introduced cDNA encoding wild-type and mutant channels into a variant of a CNS
      derived catecholamine cell line (Cath.a) known as Cath.a-differentiated. When
      cultured in serum-free medium, Cath.a-differentiated cells cease proliferation
      and undergo morphological differentiation, growing long neurites. Cath.a
      differentiated cells do not express endogenous Girk channels. Transfection of
      GIRK2(wv) resulted in the death of Cath.a-differentiated cells, in a cDNA
      concentration dependent manner. The highest concentration of Girk2(wv) cDNA
      caused loss of about half the cells, the next highest concentration one-third,
      and the least had no effect on viability. However, even the lowest concentration
      resulted in disruption of neurite outgrowth and reduced the protein products of
      co-transfected genes. High concentrations of MK801, which prevent Na(+) influx
      through the mutant channel, prevented death induced by GIRK2(wv). Cell death and
      disruption of neurite outgrowth were counteracted in GIRK2(wv)-expressing cells
      by the presence of an unrelated inwardly rectifying potassium channel, Kir2.3.
      These results are consistent with wv being a gain-of-function mutation, causing
      disruption of cellular homeostasis by mechanisms such as increased Na(+) influx
      and chronic depolarization which may in turn result in an excessive metabolic
      burden on the cell.

PMID- 15953686
TI  - Acute fluoxetine administration differentially affects brain C-Fos expression in
      fasted and refed rats.
AB  - In the present study we investigated the effect of acute fluoxetine
      administration on the expression of c-Fos in the rat brain under two different
      metabolic conditions: fed and fasting states. Wistar male rats, weighing 220+/
      30g, received i.p. injections of saline solution or fluoxetine (10mg/kg), and
      were killed 2 h later. The brains were removed after transcardiac perfusion with
      phosphate-buffered saline followed by paraformaldehyde, and were then processed
      for immunohistochemistry. Fos-like immunoreactivity was quantified by a
      computerized system. Fasted animals faced an 18-h suppression of food intake,
      while fed groups were submitted to an initial 14-h period of fast followed by a 4
      h period in which food was freely available. Both in fasting and fed states,
      fluoxetine-treated animals presented a significant increase in c-Fos expression
      in hypothalamic areas, limbic structures, circumventricular areas, and in
      mesencephalic and rhomboencephalic regions, as compared with saline-treated
      controls. The quantitative comparison of data obtained from fasted and fed
      animals showed that fasted rats treated with fluoxetine presented a higher c-Fos
      expression in the ventromedial hypothalamus and the paraventricular nuclei
      compared with the fed group, while in fluoxetine-treated fed rats c-Fos
      expression was higher in the arcuate nuclei, medial amygdala, locus coeruleus and
      dorsal raphe nuclei, as compared with fasted, fluoxetine-treated animals. These
      data indicate that the metabolic condition of the animals significantly modifies
      fluoxetine-induced brain c-Fos expression, suggesting that visceral and
      behavioral fluoxetine effects may be influenced by the metabolic state of the
      individual.

PMID- 15953687
TI  - Periaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5
      receptors modulate changes in rostral ventromedial medulla neuronal activities
      induced by subcutaneous formalin in the rat.
AB  - This study was undertaken to analyze the involvement of periaqueductal gray (PAG)
      cannabinoid or group I metabotropic glutamate receptors in the formalin-induced
      changes on the rostral ventromedial medulla (RVM) ON- and OFF-cells activities.
      S.c. injection of formalin into the hind paw produced a transient decrease (4-6
      min) followed by a longer increase (25-35 min) in tail flick latencies. Formalin
      also increased basal activity in RVM ON-cells (42+/-7%) and decreased it in OFF
      cells (35+/-4%). Intra-PAG microinjection of (R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl) pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate (WIN 55,212-2) (2 nmol/rat), a cannabinoid receptor agonist, prevented
      the formalin-induced changes in RVM cell activities. Higher dosages of WIN 55,212
      2 (4-8 nmol/rat) increased the tail flick latencies, delayed the tail flick
      related onset to ON-cell burst, and decreased the duration of OFF-cell pause.
      Furthermore, WIN 55,212-2 at a dosage of 8 nmol/rat decreased RVM ON-cell (57+/
      7%) and increased OFF-cell ongoing activities (26+/-4%). These effects were
      prevented by N-piperidino-5-(4-chlorophenyl)-1-(2,4dichlorophenyl)-4-methyl-3
      pyrazolecarboxamide SR141716A, (1 pmol/rat), a CB1 cannabinoid receptor
      antagonist, or by 2-methyl-6-(phenylethynyl)pyridine (MPEP 20 nmol/rat), a
      selective mGlu5 glutamate receptor antagonist. T7-(hydroxyimino)
      cyclopropa[b]chromen-1alpha-carboxylate ethyl ester (CPCOOE/50 nmol/rat) and (S)
      (+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385, 20 nmol/rat),
      selective mGlu1 glutamate receptor antagonists, were ineffective in preventing
      the WIN-induced effects. This study suggests that s.c. injection of formalin
      modifies RVM neuronal activities and this effect is prevented by PAG cannabinoid
      receptor stimulation. Moreover, the physiological stimulation of PAG mGlu5, but
      not mGlu1 glutamate receptors, seems to be required for the cannabinoid-mediated
      effect.

PMID- 15953688
TI  - Protection by a taurine supplemented diet from lead-induced deficits of long-term
      potentiation/depotentiation in dentate gyrus of rats in vivo.
AB  - Previous studies have demonstrated that synaptic plasticity, which includes long
      term potentiation (LTP) and depotentiation (DP) in hippocampus, is important for
      learning and memory. The purpose of this study is to evaluate the effect of
      taurine via drinking water on the lead-induced impairments of LTP and DP in rat
      dentate gyrus (DG) in vivo. The experiments were carried out in four groups of
      rats (control, lead-exposed, control and lead-exposed with a taurine-supplement
      diet, respectively). The input-output (I/O) function, excitatory postsynaptic
      potential (EPSP) and population spike (PS) amplitude were measured in the DG area
      of adult rats (60-90 days) in response to stimulation applied to the lateral
      perforant path. The results show that: 1. chronic lead exposure impaired LTP/DP
      measured on both EPSP slope and PS amplitude in DG area of the hippocampus; 2. in
      control rats, taurine had no effect on LTP/DP; 3. the amplitudes of LTP/DP of
      lead-exposed group were significantly increased by applying taurine. These
      results suggest that dietary taurine supplement could protect rats from the lead
      induced impairments of synaptic plasticity and might be a preventive medicine to
      cure the cognitive deficits induced by lead.

PMID- 15953689
TI  - Association between personality and adolescent smoking.
AB  - The present study examined the association between adolescents' personality
      traits and smoking, and tested whether this association was moderated by birth
      order or gender. Participants were 832 Dutch siblings aged 13 to 17 years
      participating at baseline assessment (T1) and at follow-up 12 months later (T2).
      Personality was assessed by applying a variable-centered approach including five
      personality dimensions (Extraversion, Agreeableness, Conscientiousness, Emotional
      Stability and Openness to Experience), and a person-oriented approach using three
      personality types (i.e., Resilients, Overcontrollers and Undercontrollers). Cross
      sectional findings indicated that Extraversion (at T1 and T2), Agreeableness (at
      T2), Conscientiousness (at T2), and Emotional Stability (at T2) were related to
      adolescent smoking. Longitudinal findings indicated that only Extraversion and
      Emotional Stability were related to onset of adolescent smoking. Using a person
      oriented approach, Overcontrollers and Undercontrollers did not differ from
      Resilients on smoking onset. No indication was found for a moderating effect of
      birth order on the association between personality and smoking. Additional
      findings showed that gender moderated the effect of Agreeableness on adolescents'
      smoking onset. Implications for prevention are also addressed.

PMID- 15953690
TI  - A novel application of quantum dots as a tool for storage of CD spectra data in
      proteomics.

PMID- 15953691
TI  - Synergistic interaction of heterozygous deletions impairs performance and confers
      susceptibility to disease at all ages.
AB  - Rare recessive conditions are more common in the offspring of cousin unions than
      in the general population even in communities in which less than 0.5% of all
      marriages are between first cousins. It is shown that if the human genome has
      30,000 genes in the haploid set then (Y+X)6/(Y)5 < 19, where X is the mean number
      of new mutations entering the human genome per generation and Y is the mean
      number of heterozygous deletions in the germ line of adults. This places an upper
      limit on X of 1.3. Functions specifying the frequency of homozygous deletions in
      the offspring of cousin and sibling unions are also derived in terms of X and Y.
      The best estimates with these three measures are that Y is between 6 and 10, and
      X between 0.5 and 1.3. Data on mutation rates in bacteria, worms, yeast, flies
      and mice are consistent with these estimates. It is argued that selection against
      heterozygous deletions must occur in order to prevent progressive build up in the
      genome; furthermore, it is postulated that the selection must be based on
      synergistic interaction. If heterozygous deletions interact synergistically to
      degrade biological performance then this has implications for human fertility,
      for polygenic disease, for the genetic basis of polygenic traits such as
      intelligence and the association between birth weight and adult disease (Barker's
      phenomenon) and the links between status and health inequality. The concept
      proposed is that a large set of genes specify each aspect of biological
      capability; the genes specify a redundant system so that one or two deletions
      will have minimal effect; but several deletions will interact synergistically to
      degrade performance and cause disease.

PMID- 15953692
TI  - A scientific paradigm for consciousness: a theory of premotor relations.
AB  - Consciousness has become a holy grail for scientific research only in the last
      few decades. In spite of the extensive recent research in the field agreement on
      a correct approach to a theory has been elusive. We all have an intuitive idea of
      what we mean by the term and at the very least relate awareness to a descriptive
      phenomenology. I present a theory of consciousness based on motor capacity. An
      organism may exert control through movement and any action it performs on its
      surroundings results in a reaction. This type of reafference generated by
      movement provides the organism with a unique opportunity to compare perceptual
      information, for example, a retinal image of a ball with what the body is telling
      the agent about the object. In other words, limb movements will describe a
      certain physical distance to the object and the shape will be conveyed by the arc
      described around it by any part of the body that comes into contact with it. The
      reafference, also called motor efference copy, can modulate neocortical networks
      strictly associated with concurrent perceptual information via input to
      thalamocortical projections. Concurrent perceptual and motor reafferent input
      provide the critical organizing principles bestowing on a neural assembly the
      capacity of conscious awareness. The cortical neural coding represents an
      interactive history and is what I call a premotor relation. It avoids the trap of
      behaviorism by emphasizing a developmental causality such that, once the networks
      are established no further motoric component is required. Supportive evidence for
      this position comes from the classic psychological studies of perceptual
      adaptation to distorting lenses facilitated by movement and elegant animal
      experiments dissociating sensorimotor development from visual exposure. One of
      the most innovative and useful conceptions advanced in the paper is a component
      theory of motor efference copy analyzing the two key parameters of any action
      namely force and proprioceptive change. There is massive neocortical input to the
      basal ganglia and cerebellum and recent research has implicated cognitive roles
      for these structures. I propose they serve the respective component parameters of
      motor efference copy. Finally, a theory of premotor relations provides a model
      for understanding how dysfunction in the basal ganglia and cerebellum relates to
      cognitive features of schizophrenia and autism, respectively. Motor dysfunction
      figures prominently in the early literature on these syndromes and I make the
      case for a fundamental causal connection between motor and cognitive symptoms.

PMID- 15953693
TI  - Cancer as a result of somatic cells fusion caused by some dietary fats and
      carbohydrates.

PMID- 15953694
TI  - Importance of timing of antiaggregant treatment in the prevention of radiation
      induced enteropathy.
AB  - Chronic radiation enteropathy (CRE) is an undesirable radiation-induced toxicity
      and a common health problem in patients with pelvic or abdominal malignancies.
      Damage to microvascular endothelial cells and connective tissue is blamed to
      cause this adverse effect. It is shown that platelets are the first cellular
      elements that initiate the homeostatic and inflammatory responses and release of
      several proinflammatory and fibrinogenic mediators. Antiplatelet agents such as
      ticlopidine and clopidogrel were shown to prevent CRE and this effect is believed
      to be directed by their activities against thrombocytes. However, recent studies
      have shown that these drugs also induce apoptosis in endothelial cells and may
      lead to decreased expression of endothelial prostacyclin and thrombomodulin (TM)
      and increased release of von Willebrand factor which are shown to be major
      contributors of coagulation process. Assuming that radiation induced apoptosis
      occur 6-10h after irradiation, we think that timing of these antiaggregant drugs
      with irradiation is important and a 6-10h interval between these may be
      beneficial to avoid this adverse interaction.

PMID- 15953695
TI  - The expression of selected non-ribosomal peptide synthetases in Aspergillus
      fumigatus is controlled by the availability of free iron.
AB  - Three non-ribosomal peptide synthetase genes, termed sidD, sidC and sidE, have
      been identified in Aspergillus fumigatus. Gene expression analysis by RT-PCR
      confirms that expression of both sidD and C was reduced by up to 90% under iron
      replete conditions indicative of a likely role in siderophore biosynthesis. SidE
      expression was less sensitive to iron levels. In addition, two proteins purified
      from mycelia grown under iron-limiting conditions corresponded to SidD (
      approximately 200 kDa) and SidC (496 kDa) as determined by MALDI ToF peptide mass
      fingerprinting and MALDI LIFT-ToF/ToF. Siderophore synthetases are unique in
      bacteria and fungi and represent an attractive target for antimicrobial
      chemotherapy.

PMID- 15953696
TI  - Two-step method for constructing unmarked insertions, deletions and allele
      substitutions in the yeast genome.
AB  - We describe three extensions of the method of site-specific genomic (SSG)
      mutagenesis. These three extensions of SSG mutagenesis were used to generate
      precise insertion, deletion, and allele substitution mutations in the genome of
      the budding yeast, Saccharomyces cerevisiae. These mutations are termed precise
      because no attached sequences (e.g., marker genes or recombination sites) are
      retained once the method is complete. Because the method is PCR-based, neither
      DNA cloning nor synthesis of long oligonucleotides is required. We demonstrated
      the efficacy of these methods by deleting an ORF, inserting the tandem affinity
      purification (TAP) tag, and replacing a wild-type allele with a mutant allele.

PMID- 15953697
TI  - Coating of a surface with 2-methacryloyloxyethyl phosphorylcholine (MPC) co
      polymer significantly reduces retention of human pathogenic microorganisms.
AB  - The present study compares the retention of four species that are often isolated
      in association with biomedical device-related infections - Staphylococcus aureus,
      Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans - to three
      different surfaces. All four bacterial species were found to bind significantly
      less well to MPC-coated surfaces than to non-coated surfaces. We attribute this
      effect to the "superhydrophilicity" of MPC-coated surfaces, whereas hydrophobic
      surfaces are well known to reduce bacterial retention and thus to inhibit a
      crucial step in the formation of bacterial biofilms that lead to biomedical
      device-related infections and complications.

PMID- 15953698
TI  - The genetic diversity of lactic acid producing bacteria in the equine
      gastrointestinal tract.
AB  - Seventy-two lactic acid producing bacterial isolates (excluding streptococci)
      were cultured from the gastrointestinal tract of six horses. Two of the horses
      were orally dosed with raftilose to induce lactic acidosis and laminitis while
      the remaining four were maintained on a roughage diet. Near complete 16S rDNA was
      amplified by PCR from the genomic DNA of each isolate. Following RFLP analysis
      with the restriction enzymes MboI, HhaI and HinfI, the PCR products from the 18
      isolates that produced L- and/or D-lactate were subsequently cloned and
      sequenced. DNA sequence analysis indicated that the majority of the isolates were
      closely related to species within the genus Lactobacillus, including
      Lactobacillus salivarius, Lactobacillus mucosae and Lactobacillus delbrueckii.
      Four isolates were closely related to Mitsuokella jalaludinii. Lactic acid
      producing bacteria (LAB) from the equine gastrointestinal tract was dominated by
      representatives from the genus Lactobacillus, but also included D-lactate
      producing bacteria closely related to M. jalaludinii. Identification and
      characterization of LAB from the equine gastrointestinal tract should contribute
      to our understanding and management of fermentative acidosis, ulceration of the
      stomach and laminitis.

PMID- 15953699
TI  - recA gene expression in a streptomycete is mediated by the unusual C-terminus of
      RecA protein.
AB  - Streptomyces RecA proteins are characterized by a conserved, positively charged
      extension of unknown function appended at their C-termini. To investigate the
      function of this element, we introduced the Streptomyces rimosus recA gene and
      its mutant form encoding the protein with a C-terminal deletion into S. rimosus.
      Both transcript and protein levels were dramatically increased in the strain
      expressing the truncated gene compared to the strain bearing the wild-type recA,
      indicating involvement of the characteristic C-terminal extension in regulating
      the recA expression in Streptomyces. Considering that RecA acts as a major
      regulator of DNA damage response in bacteria, this mode of regulation is expected
      to have broader implications and significance that outreaches our current
      understanding of RecA autoregulation.

PMID- 15953700
TI  - Dissemination of the superantigen encoding genes seeL, seeM, szeL and szeM in
      Streptococcus equi subsp. equi and Streptococcus equi subsp. zooepidemicus.
AB  - Bacterial superantigens are one of the major virulence factors produced by
      Streptococcus pyogenes and Staphylococcus aureus. The two novel superantigen
      encoding genes seeM and seeL were described for S. equi subsp. equi which is
      known as the causative agent of strangles in equids. In the present study
      previously characterized S. equi subsp. equi strains and strains of various other
      animal pathogenic streptococcal species and subspecies were investigated for the
      presence of the superantigen encoding genes seeM and seeL by polymerase chain
      reaction. According to these studies seeL and seeM appeared to be a constant
      characteristic of all investigated S. equi subsp. equi strains. Surprisingly, one
      S. equi subsp. zooepidemicus strain (S.z. 122) was also positive for both genes.
      The species identity of this S. equi subsp. zooepidemicus strain could
      additionally be confirmed by sequencing the 16S rRNA gene and the 16S-23S rDNA
      intergenic spacer region. The superantigen encoding genes could not be found
      among additionally investigated S. equi subsp. zooepidemicus strains or among
      strains of seven other streptococcal species. The seeL and seeM genes of the S.
      equi subsp. equi strain S.e. CF32 and the genes szeL and szeM of the S. equi
      subsp. zooepidemicus strain S.z. 122 were cloned and sequenced. A sequence
      comparison revealed a high degree of sequence homology between seeL, szeL, speL
      and seeM, szeM and speM, respectively. The superantigenic toxins L and M seemed
      to be widely distributed virulence factors of S. equi subsp. equi, rare among S.
      equi subsp. zooepidemicus but did not occur among a number of other animal
      pathogenic streptococcal species.

PMID- 15953701
TI  - Assessment of DNA damage in peripheral blood lymphocytes of individuals
      susceptible to arsenic induced toxicity in West Bengal, India.
AB  - Assessment of DNA damage was carried out using alkaline comet assay in
      lymphocytes of 30 individuals exposed to high levels of arsenic (247.12+/-18.93
      microg/l) through contaminated groundwater in North 24 Parganas district, West
      Bengal, India. All of them exhibited high arsenic contents in nail (4.20+/-0.67
      microg/g), hair (2.06+/-0.20 microg/g) and urine (259.75+/-33.89 microg/l)
      samples and manifested various arsenical skin lesions. Unexposed samples were
      collected from 30 residents of the unaffected East Midnapur district with very
      little or no exposure to arsenic (7.69+/-0.49 microg/l) in drinking water. The
      results were evaluated principally by manual analysis of comets and partly by
      computerized image analysis. Both the analytical methods exhibited a high degree
      of agreement in results. The exposed participants expressed significantly higher
      DNA damage (p < 0.01) in their lymphocytes than the unexposed participants.
      Alkaline comet assay was also combined with formamidopyrimidine-DNA glycosylase
      enzyme digestion to confirm that arsenic induced oxidative base damage in the
      lymphocytes. Significant positive trend effects of comet lengths in relation to
      arsenic levels in water prove that DNA damage can be used as a sensitive
      biomarker of arsenic exposure. This study demonstrates that arsenic induced
      significant DNA damage in the exposed participants, which could correspond to a
      higher susceptibility to arsenic induced toxicity and carcinogenicity.

PMID- 15953702
TI  - Assay of the synthetic estrogen fosfestrol in pharmaceutical formulations using
      capillary electrophoresis.
AB  - This study reports--for the first time--a capillary electrophoretic method for
      the determination of fosfestrol, a synthetic estrogen used in the treatment of
      metastatic prostate cancer. The effects of the carrier ion concentration,
      injected volume and applied voltage were studied and optimized. A 10 mM sodium
      tetraborate solution was selected as the carrier electrolyte solution, while the
      sample was injected hydrodynamically by applying a 20 mmHg vacuum for 1 s. The
      driving voltage was 30 kV and the absorbance of the analyte (peak height) was
      monitored at 240 nm. Under the above-mentioned conditions, the migration time of
      fosfestrol was 6.6 min. Linearity was achieved in the analyte range 3-150 mgL(-1)
      with the detection limit being 1 mgL(-1). The proposed method is adequately
      precise (s(r)=2.8% at 100 mgL(-1) fosfestrol, n=10) without the use of an
      internal standard and was applied to the determination of fosfestrol in a
      pharmaceutical formulation. The results obtained by the proposed method were in
      good agreement with those derived from the USP reference method.

PMID- 15953703
TI  - The simultaneous separation and determination of five quinolone antibiotics using
      isocratic reversed-phase HPLC: application to stability studies on an ofloxacin
      tablet formulation.
AB  - A rapid and reliable HPLC method was developed for the simultaneously separation
      and quantitation of five quinolones antibiotics; nalidixic acid, norfloxacin,
      ofloxacin, ciprofloxacin and lomefloxacin. All five tablet formulations of
      individual quinolone antibiotics were routinely assayed without interference. The
      calibration curves were linear (r2> or =0.999) over the concentration range of
      1.20-4.8 mg/100 ml. Selectivity, precision, sensitivity and accuracy were
      established and the method is stability indicating with respect to ofloxacin. The
      limit of detection and quantitation for ofloxacin was 18 and 36 microg/100 ml,
      respectively. The separation was performed on a Phenomenex ODS C18 column using
      an isocratic, ion-pairing mobile phase consisting of 35% (v/v) aqueous
      acetonitrile together with tetrabutylammonium acetate, sodium dodecyl sulphate
      and citric acid (pH* 3.4). All analyses were conducted at ambient temperature and
      was monitored using a Diode Array UV/VIS detector set at wavelengths 235, 254,
      275 and 300 nm.

PMID- 15953704
TI  - Determination of hydrogen peroxide scavenging activity of cinnamic and benzoic
      acids employing a highly sensitive peroxyoxalate chemiluminescence-based assay:
      structure-activity relationships.
AB  - A series of cinnamic acids along with their corresponding benzoate analogues were
      tested for their ability to scavenge hydrogen peroxide (H(2)O(2)), by using a
      highly sensitive, peroxyoxalate chemiluminescence assay. Among benzoic acid
      derivatives, vanillic acid (3-hydroxy-4-methoxybenzoic acid) was found to be the
      most efficient H(2)O(2) scavenger with its hydrogen peroxide scavenging activity
      (SA(HP)) being 170.20 microM(-1), whereas protocatechuic acid (3,4
      dihydroxybenzoic acid) exhibited the weakest activity (5.90 microM(-1)). Caffeic
      acid (3,4-dihydroxycinnamic acid) was the strongest antioxidant amongst cinnamate
      derivatives with a SA(HP) = 8.2 microM(-1), as opposed to m-coumaric acid (2
      hydroxycinnamic acid), which was found to be a poor hydrogen peroxide scavenger
      (SA(HP) = 0.18 microM(-1)). Comparison between the two groups revealed that
      benzoate derivatives are much stronger hydrogen peroxide quenchers in relation
      with their cinnamate analogues, and this finding was discussed on a basis of
      structure-activity relationships and comparative assessment of other antioxidant
      characteristics.

PMID- 15953705
TI  - Simultaneous determination of loratadine and pseudoephedrine sulfate in human
      plasma by liquid chromatography-electrospray mass spectrometry for
      pharmacokinetic studies.
AB  - To support the pharmacokinetic and bioavailability study of an extended-release
      loratadine (LOR)/pseudoephedrine sulfate (PES) tablet, a high performance liquid
      chromatographic-electrospray ionisation-mass spectrometric method (LC-MS) was
      developed for the simultaneous determination of LOR and PES in human plasma.
      Diazepam (DP) and phenylpropanolamine (PPA) were used as internal standards for
      LOR and PES, respectively. Analytes were extracted from alkalized human plasma by
      liquid/liquid extraction using ethyl ether. Chromatographic separation was
      performed on an ODS column at flow rate of 0.2 ml/min. The total chromatographic
      run time was 10.5 min with the retention time of 7.1 min and 6.2 min for LOR and
      DP, respectively, and 2.2 min for both of PES and PPA. The LOQ was 10 pg/ml and
      50 pg/ml for LOR and PES, respectively. The method is accurate and precise enough
      for its intended purpose.

PMID- 15953706
TI  - Neuropsychological performance in adult attention-deficit hyperactivity disorder:
      meta-analysis of empirical data.
AB  - Attention-deficit hyperactivity disorder (ADHD) is increasingly recognized not
      only in children but also in adults. Neuropsychological tests are important tools
      to quantify the attentional and/or cognitive deficits of patients compared to
      controls. The present meta-analysis integrates 24 empirical studies reporting
      results of at least one of 50 standard neuropsychological tests comparing adult
      ADHD patients with controls. The 50 tests were categorized into the following 10
      functional domains: verbal ability, figural problem solving, abstract problem
      solving, executive function, fluency, simple attention, sustained attention,
      focused attention, verbal memory, figural memory. For each domain a pooled effect
      size d' was calculated. Complex attention variables and verbal memory
      discriminated best between ADHD patients and controls. Effect sizes for these
      domains were homogeneous and of moderate size (d' between 0.5 and 0.6). In
      contrast to results reported in children, executive functions were not generally
      reduced in adult ADHD patients.

PMID- 15953707
TI  - Investigation of corpus callosum in schizophrenia with diffusion imaging.
AB  - BACKGROUND: Corpus callosum (CC) is the main white matter commissure between the
      two cerebral hemispheres. Abnormalities of CC have been shown in schizophrenia
      patients by magnetic resonance imaging (MRI) studies. We here further
      investigated CC organization with diffusion imaging (DWI) in a sample of
      schizophrenia patients recruited from the epidemiologically defined catchment
      area of South Verona, Italy. METHODS: Sixty-seven patients with schizophrenia and
      70 normal controls were studied. Regions of interests (ROIs), standardized at 5
      pixels, were placed in CC on the non-diffusion weighted echoplanar images (b = 0)
      and were then automatically transferred to the corresponding maps to obtain the
      apparent diffusion coefficient (ADC) of water molecules. RESULTS: ADC measures
      for all callosal subregions in schizophrenia patients were significantly greater
      compared to normal controls (ANCOVA, p < 0.05). Positive symptoms significantly
      correlated with anterior callosal ADC measures (partial correlation analyses, p <
      0.05). CONCLUSIONS: These findings support the existence of widespread
      microstructure disruption of CC in schizophrenia, which may ultimately lead to
      inter-hemispheric misconnection, and also suggest a specific role of anterior
      transcallosal disconnectivity in underlying positive symptoms. Future
      longitudinal MRI studies in high risk and first-episode patients together with
      neurophysiological tests are indicated to further examine CC anatomical
      abnormalities and inter-hemispheric transmission in schizophrenia.

PMID- 15953708
TI  - Significant increases in the levels of liver enzymes in mice treated with anti
      tuberculosis drugs.
AB  - Besides the long-term effectiveness of a given compound, safety is a very
      important feature to consider when developing new compounds for chemotherapy
      against tuberculosis. Reports of fatal and severe liver injury associated with
      rifampicin-pyrazinamide (RIF-PZA) treatment regimens for latent tuberculosis
      infections prompted this study to evaluate whether a mouse model has any
      potential as a tool to assess liver injury following extensive exposure to
      tuberculosis drugs. Mice were administered high doses of existing drug regimens
      for latent tuberculosis over a relatively short time period. Alanine
      aminotransferase (ALT), aspartate aminotransferase and bilirubin levels were
      determined after 2 weeks and 4 weeks of treatment in serum samples collected from
      uninfected mice as well as mice infected with Mycobacterium tuberculosis. ALT
      levels increased significantly after a RIF-PZA treatment regimen for 4 weeks in
      uninfected mice and after 2 weeks in infected mice. Bilirubin serum levels were
      also significantly elevated in the M. tuberculosis-infected mice after 4 weeks of
      RIF-PZA treatment. The data obtained indicate that changes in serum enzyme levels
      in mice after extensive exposure to tuberculosis drugs could be useful as an
      initial indicator of drug-related hepatotoxicity.

PMID- 15953709
TI  - Antimicrobial resistance of Salmonella enterica group C strains isolated from
      humans in Turkey, 2000-2002.
AB  - Fifty-three Salmonella enterica group C isolates obtained from various human
      samples (47 stool, 4 blood and 2 urine) in ten provinces of Turkey between 1 July
      2000 and 30 June 2002 were serotyped and resistance to antimicrobials was
      investigated by agar dilution tests. The isolates were identified as S.
      Choleraesuis (11), S. Hadar (7), S. Irumu (4), S. Virchow (3), S. Tallahassee
      (3), S. Paratyphi C (2), S. Braenderup (2), S. Othmarschen (2), S. Menston (2),
      S. Concord (2), S. Infantis (2), S. Kottbus (2), S. Edinburg (1), S. Oranienburg
      (1), S. Muenchen (1) and S. Malmoe (1). Antimicrobial resistance rates of S.
      enterica groups C1 and C2 were high for ampicillin (26% and 60%, respectively),
      amoxicillin/clavulanic acid (11% and 40%), chloramphenicol (16% and 27%) and
      tetracycline (3% and 40%). The percentages of strains sensitive to all
      antimicrobials were 58% and 33%, respectively. Multiresistance was not observed
      in group C1 isolates, but the rate of multiresistant isolates was 13% in group
      C2. The rate of decreased ciprofloxacin susceptibility (CipL) was 61% in
      serogroup C1 and 20% in serogroup C2. These results indicated that S. enterica
      group C infections in humans were not infrequent in Turkey and that multiple
      antimicrobial resistance was common within these strains.

PMID- 15953710
TI  - Preattentive representation of feature conjunctions for concurrent spatially
      distributed auditory objects.
AB  - The role of attention in conjoining features of an object has been a topic of
      much debate. Studies using the mismatch negativity (MMN), an index of detecting
      acoustic deviance, suggested that the conjunctions of auditory features are
      preattentively represented in the brain. These studies, however, used
      sequentially presented sounds and thus are not directly comparable with visual
      studies of feature integration. Therefore, the current study presented an array
      of spatially distributed sounds to determine whether the auditory features of
      concurrent sounds are correctly conjoined without focal attention directed to the
      sounds. Two types of sounds differing from each other in timbre and pitch were
      repeatedly presented together while subjects were engaged in a visual n-back
      working-memory task and ignored the sounds. Occasional reversals of the frequent
      pitch-timbre combinations elicited MMNs of a very similar amplitude and latency
      irrespective of the task load. This result suggested preattentive integration of
      auditory features. However, performance in a subsequent target-search task with
      the same stimuli indicated the occurrence of illusory conjunctions. The
      discrepancy between the results obtained with and without focal attention
      suggests that illusory conjunctions may occur during voluntary access to the
      preattentively encoded object representations.

PMID- 15953711
TI  - Age-related reorganization of encoding networks directly influences subsequent
      recognition memory.
AB  - Functional magnetic resonance imaging was used to link performance-related brain
      activity during two word encoding tasks to subsequent recognition for those words
      in young and older adults. There were no significant group differences in
      performance during encoding, but the young subjects performed better than the
      older at the recognition task. Performance-related brain networks strongly
      differed between the two groups. In young subjects, there were two networks
      associated with performance, one related to encoding (mainly involving premotor
      and parietal brain regions) and the other to recognition (involving middle
      frontal, and lateral and medial temporal regions), whereas the network for older
      subjects (including prefrontal, premotor, lateral and medial temporal regions)
      was associated both with encoding and recognition. Areas in this network strongly
      overlapped with those supporting recognition in the young subjects (e.g., medial
      temporal lobe), suggesting that older subjects may have recruited these areas to
      maintain performance during encoding. However, this reorganization of brain
      networks appears to have come at the cost of subsequent recognition.

PMID- 15953712
TI  - Development of a single unit extended release formulation for ZK 811 752, a
      weakly basic drug.
AB  - ZK 811 752, a potent candidate for the treatment of autoimmune diseases,
      demonstrated pH-dependent solubility. The resulting release from conventional
      matrix tablets decreased with increasing pH-values of the dissolution medium. The
      aim of this study was to overcome this problem and to achieve pH-independent drug
      release. Three different polymers were used as matrix formers, the partly water
      soluble and poorly swellable mixture of polyvinylacetate/polyvinylpyrrolidone,
      the water-insoluble and almost unswellable ethylcellulose (EC) and the water
      soluble and highly swellable hydroxypropyl methylcellulose (HPMC). To solve the
      problem of pH-dependent solubility different organic acids, such as fumaric,
      tartaric, adipic, glutaric and sorbic acid were added to the drug-polymer system.
      The addition of organic acids to all three matrix formers was found to maintain
      low pH-values within the tablets during release of ZK 811 752 in phosphate buffer
      pH 6.8. Thus, the micro-environmental conditions for the dissolution of the
      weakly basic drug were kept almost constant. An extended release matrix tablet
      for ZK 811 752 consisting of drug, polymer and organic acid providing the desired
      pH-independent drug release has been developed.

PMID- 15953713
TI  - The mechanism of action of Kahalalide F: variable cell permeability in human
      hepatoma cell lines.
AB  - Kahalalide F (KF) is a small natural peptide that showed activity in vitro and in
      vivo. The dose-limiting toxicity in clinical trials was transaminitis. We
      investigated the cytotoxicity of KF in cell lines from breast, ovary, prostate
      and colon cancers, but focused on hepatoma cell lines, performing mechanistic
      studies in HepG2 (IC50 = 0.3 microM) and PLC/PRF/5C (IC50 = 5 microM). Following
      KF exposure, HepG2 cells demonstrated profound ATP depletion, associated with
      cell swelling and cell blebbing, and increased permeability to propidium iodide
      (PI), annexin V (AV) and release of lactate dehydrogenase (LDH). PLC/PRF/5C cells
      retained their cell structure, but were permeable to PI and, following exposure
      to high concentrations of KF, to AV. The pattern of cell permeability is similar
      to maitotoxin, another small cytotoxic peptide, but the differential effects on
      the cell membrane induced by KF in HepG2 and PLC/PRF/5C suggest specific
      interactions with membranes or proteins. This could lead to better drug design
      aimed at exploiting the potential for cell selectivity.

PMID- 15953714
TI  - Effects of early intervention with epoetin alfa on transfusion requirement,
      hemoglobin level and survival during platinum-based chemotherapy: Results of a
      multicenter randomised controlled trial.
AB  - This work was conducted to evaluate the effect of early intervention with epoetin
      alfa (EPO) on transfusion requirements, hemoglobin level (Hb), quality of life
      (QOL) and to explore a possible relationship between the use of EPO and survival,
      in patients with solid tumors receiving platinum-based chemotherapy. Three
      hundred and sixteen patients with Hb12.1g/dL were randomised 2:1 to EPO 10000 IU
      thrice weekly subcutaneously (n = 211) or best supportive care (BSC) (n = 105).
      The primary end point was proportion of patients transfused while secondary end
      points were changes in Hb and QOL. The protocol was amended before the first
      patient was recruited to also prospectively collect survival data. EPO therapy
      significantly decreased transfusion requirements (P < 0.001) and increased Hb (P
      < 0.005). EPO-treated patients had significantly improved QOL compared with BSC
      patients (P < 0.05). Kaplan-Meier estimates showed no differences in 12-month
      survival (P = 0.39), despite a significantly greater number of patients with
      metastatic disease in the EPO group (78% vs. 61%, P = 0.001). EPO was well
      tolerated. This study has shown that early intervention with EPO can result in a
      significant reduction of transfusion requirements and increases in Hb and QOL in
      patients with mild anemia during platinum-based chemotherapy.

PMID- 15953715
TI  - Chemoprevention of genome, transcriptome, and proteome alterations induced by
      cigarette smoke in rat lung.
AB  - Post-genomic methodologies have provided novel tools for evaluating safety and
      efficacy of cancer chemopreventive agents. We exposed rats to environmental
      cigarette smoke (ECS) for 28 days, with or without oral administration of N
      acetylcysteine (NAC). As assessed by 32P-postlabelling, ECS caused a 10-fold
      increase of DNA adduct levels, which were significantly reduced by NAC. Of 518
      proteins tested by antibody microarray, ECS stimulated 56 activities involved in
      stress response, protein removal, cell replication, apoptosis, phagocytosis, and
      immune response. NAC alone did not change the amounts of any protein, whereas it
      significantly decreased the amounts of 6 ECS-induced proteins. The intensity of
      expression of 278 related genes, assessed by cDNA microarray, was significantly
      correlated with protein amounts. These observed molecular alterations, which can
      be attenuated by NAC, represent in part adaptive responses and in part reflect
      mechanisms contributing to the pathogenesis of smoke-related diseases, including
      lung cancer, asthma, chronic bronchitis, and emphysema.

PMID- 15953716
TI  - Standardised FDG uptake: a prognostic factor for inoperable non-small cell lung
      cancer.
AB  - The aim of this study was to investigate the relationship between standardised
      uptake value (SUV) obtained from [(18)F]fluorodeoxyglucose positron emission
      tomography (FDG PET) and treatment response/survival of inoperable non-small cell
      lung cancer (NSCLC) patients treated with high dose radiotherapy. Fifty-one
      patients were included recording stage, performance, weight loss, tumour volume,
      histology, lymph node involvement, SUV, and delivered radiation dose. The maximum
      SUV (SUV(max)) within the primary tumour was a sensitive and specific factor for
      predicting treatment response. Apart from SUV(max), stage and performance were
      also independent predictive factors for treatment response. In a multivariate
      disease-specific survival (DSS) analysis, SUV(max) (P = 0.01), performance status
      (P = 0.008) and stage (P = 0.04) were prognostic factors. For overall survival
      (OS), SUV(max) (P = 0.001) and performance (P = 0.06) were important prognostic
      factors. SUV(max) was an important prognostic factor for survival of inoperable
      NSCLC patients and a predictive factor for treatment response. Although the
      number of patients was small, the treatment was not homogeneous and the use of
      FDG SUV may have had constraints, we still conclude that the FDG SUV is
      potentially a good indicator for selecting patients for different treatment
      strategies.

PMID- 15953717
TI  - Beer constituents as potential cancer chemopreventive agents.
AB  - Beer is a complex alcoholic beverage made from barley (malt), hop, water and
      yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20
      30%). Structural classes include simple phenols, benzoic- and cinnamic acid
      derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins,
      (prenylated) chalcones and flavonoids as well as alpha- and iso-alpha-acids
      derived from hop. Compounds belonging to different structural classes have
      distinct profiles of biological activity in in vitro test systems, and in
      combination might lead to enhanced effects. Scientific evidence has accumulated
      over the past 10 years pointing to the cancer preventive potential of selected
      hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and
      isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with
      these compounds relevant to inhibition of carcinogenesis at the initiation,
      promotion and progression phases, as well as results from in vivo studies on
      metabolism, bioavailability and efficacy are summarised in this review.

PMID- 15953718
TI  - Bioaccumulation of heavy metals in Dactylis glomerata L. growing in a calcareous
      soil amended with sewage sludge.
AB  - The total and DTPA-extractable concentrations of Pb, Ni, Zn, Cu, Cr and Cd were
      measured in a calcareous soil amended with different doses of sewage sludge under
      field conditions. The same metals were also measured in the roots and leaves of
      Dactylis glomerata at the end of the first vegetative period after the sludge was
      added. The root concentrations of all the metals were unrelated to their
      concentrations in the soil. Leaf concentrations of Zn and Cr correlated with
      total (Zn) and DTPA-extractable (Zn and Cr) concentrations in the soil. DTPA
      extraction did not appear to be very useful for evaluating the bioavailability of
      metals in this kind of soil as it gave very low correlation coefficients with
      leaf content (r = 0.684, P = 0.0049 for Zn and r = 0.557, P = 0.0249 for Cr).
      Concentrations of Pb, Ni, Cu, and Cd in roots and leaves of Dactylis glomerata
      were unrelated to the total or DTPA-extractable concentrations in the sludge
      amended soil.

PMID- 15953719
TI  - Production of xylanase and protease by Penicillium janthinellum CRC 87M-115 from
      different agricultural wastes.
AB  - Five agricultural wastes were evaluated in submerged fermentation for xylanolytic
      enzymes production by Penicillium janthinellum. The wastes were hydrolyzed in
      acid medium and the liquid fraction was used for cultivation. Corn cob (55.3
      U/mL) and oat husk (54.8 U/mL) were the best inducers of xylanase. Sugar cane
      bagasse (23.0 U/mL) and corn husk (23.8 U/mL) were moderately good, while cassava
      peel was negligible. Protease production was very low in all agro-industrial
      residues. The maximum biomass yields were 1.30 and 1.17 g/L for cassava peel and
      corn husk after 180 h, respectively. Xylanolytic activity showed a cell growth
      associated profile.

PMID- 15953720
TI  - Determination and comparison of sludge reduction rates caused by microfaunas'
      predation.
AB  - Using micorfauna to reduce excess sludge is a potentially effective ecological
      technology and scaling the rate of sludge reduction rate is the first step. A
      method to scale the rate of sludge reduction caused by microfauna was proposed,
      and comparison of sludge reduction rates induced by four microfaunas was carried
      out. The principle of this method is based on the change of carbon forms. The
      rate of sludge reduction was correlated with the rate at which solids were
      changed into liquid and gas. Four microfaunas, including Aeolosoma hemprichi,
      Daphnia magna, Tubifex tubifex and Physa acuta, were cultured with sterilized
      sludge in a covered sterilized bottle and were then isolated from the atmosphere
      above the liquid phase. The rates of sludge reduction using the four microfaunas
      were 0.8, 0.18, 0.54 and 0.1 mg-sludge/(mg-Microfauna d), respectively, changing
      with the microfaunas' phylum or class and body size. Based on the change of
      carbon (C) forms, the proposed method produced accurate results similar to those
      produced using the direct measuring method.

PMID- 15953721
TI  - Determination of the energy potential of gases produced in the pyrolysis
      processes of the vegetal carbon manufacture industry.
AB  - In this work, a pyrolysis plant located in Valverde de Leganes, Badajoz (SW
      Spain) was studied. At present, only the solid phase obtained by pyrolysis finds
      an application as domestic fuel. In order to analyze the feasibility of a further
      energetic exploitation of the plant under study, the gases flowing through the
      chimneys were collected at different times throughout the pyrolysis process.
      Next, they were characterized and quantified by gas chromatography, the energy
      potential of each of the gases being determined. According to the results
      obtained in this study, a total energy potential of 5.6 x 10(7) MJ (i.e., 1.78
      MW(t)) might be generated yearly. Hence, considering an overall process yield
      equal to 20%, up to 358 KW(e) would be produced. This power would supply enough
      electric energy to the industry, the remaining being added to the common electric
      network.

PMID- 15953722
TI  - Discovery of 3-OH-3-methylpipecolic hydroxamates: potent orally active inhibitors
      of aggrecanase and MMP-13.
AB  - A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and
      aggrecanase was designed based on the observation of increased aggrecanase
      activity with substitution at the 3-position of the piperidine ring. Potency
      versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide
      group that binds in the S1' pocket. These compounds also possess markedly
      improved bioavailability and lower metabolic clearance compared to analogous 3,3
      dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to
      lowered lipophilicity proximal to the metabolically labile hydroxamic acid.
      Synthesis, structure activity relationships, and in vivo efficacy data are
      described.

PMID- 15953723
TI  - 6-Aryl-4-methylsulfanyl-2H-pyran-2-one-3-carbonitriles as PPAR-gamma activators.
AB  - Various 6-aryl-3-cyano/methoxycarbonyl-4-methylsulfanyl-2H-pyran-2-ones have been
      synthesized as a potential substitute of 2,4-thiazolidinedione head group to
      express potent PPAR-gamma transactivation response. Some of the screened
      compounds have shown promising PPAR-gamma agonistic activity.

PMID- 15953724
TI  - Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1)
      derived from MK-886.
AB  - A series of potent and selective inhibitors of the inducible microsomal PGE2
      synthase (mPGES-1) has been developed based on the indole FLAP inhibitor MK-886.
      Compounds 23 and 30 inhibit mPGES-1 with potencies in the low nanomolar range and
      with selectivities of at least 100-fold compared to their inhibition of mPGES-2,
      thromboxane synthase and binding affinity to FLAP. They also block the production
      of PGE2 in cell based assays but with a decreased potency and more limited
      selectivity compared to the enzyme assays.

PMID- 15953725
TI  - Syntheses of NAMDA derivatives inhibiting NO production in BV-2 cells stimulated
      with lipopolysaccharide.
AB  - Sixteen derivatives of N-acetyl-3-O-methyldopamine (NAMDA), an inhibitor of BH4
      synthesis, were designed and synthesized. The ability of these derivatives to
      inhibit NO and BH4 production by lipopolysaccharide-stimulated BV-2 microglial
      cells was determined. While NAMDA at 100 microM inhibited NO and BH4 production
      by only about 20%, its catecholamide 8, indole 23 derivative, 13, and N-acetyl
      tetrahydroisoquinoline 25 inhibited the NO production by >50% at the same
      concentration. In particular, 13 and 25 inhibited both NO and BH4 production to
      similar degrees, which suggested that these compounds might inhibit NO production
      by blocking BH4-dependent dimerization of the newly synthesized iNOS monomer.

PMID- 15953726
TI  - Discovery and SAR of 4-amino-2-biarylbutylurea MCH 1 receptor antagonists through
      solid-phase parallel synthesis.
AB  - -4-Amino-2-arylbutylbenzamides such as 1 were identified as micromolar MCH 1
      receptor (MCH1R) antagonists via screening using a scintillation proximity assay
      based on [125I]-MCH binding to recombinant, human MCH1R. Subsequent lead
      optimization efforts using solid-phase parallel synthesis resulted in the defined
      structure-activity relationships and the identification of 4-amino-2
      biarylbutylureas, such as 11g, as potent single digit nanomolar MCH1R
      antagonists.

PMID- 15953727
TI  - Potential new antitumor agents from an innovative combination of camphorato, a
      ramification of traditional Chinese medicine, with a platinum moiety.
AB  - Eight new camphorato platinum complexes have been synthesized and evaluated for
      their in vitro cytotoxicity against HL-60 human leukemia, 3AO human ovarian
      carcinoma, BEL-7402 human hepatocarcinoma, and A549 human lung carcinoma cell
      lines. Most complexes showed good cytotoxic activity against the above-selected
      cell lines. Among the complexes, two compounds were assayed for their in vivo
      antitumor activity against LS-174T human colon carcinoma cells implanted in mice.
      One complex exhibited not only higher in vivo antitumor activity, but also less
      toxicity than oxaliplatin when it was administered intravenously at a dose of 6
      mg/kg three times.

PMID- 15953728
TI  - Hydrophobic and electronic factors in the design of dialkylglycine decarboxylase
      mimics.
AB  - The first functional catalytic mimic of the enzyme dialkylglycine decarboxylase
      is described. This system utilizes a hydrophobically modified polyethylenimine
      polymer, a pyridoxamine cofactor, and a 2-aryl-2-alkylglycine sacrificial amine
      source to convert alpha-keto acids to alpha-amino acids at biologically relevant
      temperatures with multiple turnovers of the pyridoxamine catalyst. The effects of
      hydrophobic and electronic factors in the 2,2-disubstituted sacrificial amine
      source and the pyridoxamine catalyst on turnover frequency and turnover number
      are explored.

PMID- 15953729
TI  - Tetrabutylammonium fluoride-assisted rapid N9-alkylation on purine ring:
      application to combinatorial reactions in microtiter plates for the discovery of
      potent sulfotransferase inhibitors in situ.
AB  - Tremendous efforts have been invested in the synthesis of purine libraries due to
      their importance in targeting various enzymes involved in different diseases and
      cellular processes. The synthesis of N9-alkylated purine scaffolds relied mostly
      on Mitsunobu conditions with a variety of alcohols or strong basic conditions
      with different organic halides. A more reliable and efficient way for the
      synthesis of N(9)-alkylated purine scaffolds is reported. This method uses
      tetrabutylammonium fluoride (TBAF) to assist such chemistry. In many cases, the
      reactions were completed within 10 min and gave the desired product in high yield
      and selectivity. Moreover, these mild reaction conditions permitted its use in
      combinatorial reactions in microtiter plates followed by in situ screening for
      the discovery of potent sulfotransferase inhibitors.

PMID- 15953730
TI  - RO4383596, an orally active KDR, FGFR, and PDGFR inhibitor: synthesis and
      biological evaluation.
AB  - (+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4
      dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective
      inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR.
      This agent has an excellent pharmacokinetic profile and is highly efficacious in
      rodent models of angiogenesis upon oral administration.

PMID- 15953731
TI  - Bicistronic lentiviral vector corrects beta-hexosaminidase deficiency in
      transduced and cross-corrected human Sandhoff fibroblasts.
AB  - Sandhoff disease is an autosomal recessive neurodegenerative disease
      characterized by a GM2 ganglioside intralysosomal accumulation. It is due to
      mutations in the beta-hexosaminidases beta-chain gene, resulting in a beta
      hexosaminidases A (alphabeta) and B (betabeta) deficiency. Mono and bicistronic
      lentiviral vectors containing the HEXA or/and HEXB cDNAs were constructed and
      tested on human Sandhoff fibroblasts. The bicistronic SIV.ASB vector enabled a
      massive restoration of beta-hexosaminidases activity on synthetic substrates and
      a 20% correction on the GM2 natural substrate. Metabolic labeling experiments
      showed a large reduction of ganglioside accumulation in SIV.ASB transduced cells,
      demonstrating a correct recombinant enzyme targeting to the lysosomes. Moreover,
      enzymes secreted by transduced Sandhoff fibroblasts were endocytosed in deficient
      cells via the mannose 6-phosphate pathway, allowing GM2 metabolism restoration in
      cross-corrected cells. Therefore, our bicistronic lentivector supplying both
      alpha- and beta-subunits of beta-hexosaminidases may provide a potential
      therapeutic tool for the treatment of Sandhoff disease.

PMID- 15953732
TI  - Ethanol perturbs the secretory pathway in astrocytes.
AB  - Ethanol exposure induces retention of glycoproteins in growing astrocytes. We
      examined the intracellular sites at which this retention occurs and investigated
      whether this effect is accompanied by alterations in the Golgi complex and
      microtubular system. We studied the effects of ethanol on the Golgi complex
      structure, as well as on the secretory pathway functionality by monitoring both
      the transport of the VSV-G protein and the protein levels of several molecules
      involved in the regulation of this pathway. Ethanol was found to delay VSV-G
      transport, modify Golgi complex morphology, and reduce the number of secretory
      vesicles. Moreover, ethanol affected the levels of mannosidase II, p58, betaCOP,
      rbet1, and several Rab GTPases. It also affected microtubule organization and
      polymerization and the levels of the motor proteins kinesin and dynein. Most of
      these effects were dose-dependent. These alterations, together with those
      previously reported concerning biosynthesis of glycoconjugates, provide novel
      insights into how ethanol impairs brain development.

PMID- 15953733
TI  - Factors influencing the survival of cryopreserved homografts. The second
      homograft performs as well as the first.
AB  - OBJECTIVE: To determine the life span of cryopreserved homografts implanted in
      the right ventricular outflow tract and the factors influencing it. METHODS: From
      1989 through 2003, we reconstructed the pulmonary valve with 301 homografts in
      272 patients (median age 13 years; range 4 days-69 years). Indications were
      tetralogy of Fallot (136), truncus (23), Rastelli repair (11), double outlet
      ventricle (13), endocarditis (5), and the Ross operation (84). Median follow-up
      was 5.7 years (range 0-14). We analyzed possible predictors of graft replacement
      by simple and multiple Cox regression. RESULTS: Actuarial survival was 96+/-1.2%
      at 1, 95+/-1.4% at 5, and 94+/-1.5% at 10 years follow-up. Three homografts were
      explanted because of endocarditis (excluded from the analysis). Freedom from
      explantation was 99.6+/-0.4% at 1, 94.5+/-1.7% at 5, and 81.8+/-4.1% at 10 years.
      Variables, significantly related to explantation in the univariate analysis, were
      younger age, small graft size, implantation in a non-anatomical position, the
      aortic donor homograft, a shorter aortic cross-clamp time and the implantation of
      a second homograft. In the multiple model, non-anatomical position (P=0.001),
      smaller graft size (P<0.0001) or younger age (on square root scale, P<0.0001) and
      clamp time (P=0.01) remain as independent risk factors. Immunological variables,
      like blood group incompatibility, implantation of a second homograft and short
      warm ischemic time were not significant. CONCLUSIONS: The life span of a
      cryopreserved homograft is determined by graft size (correlates with age) and the
      non-anatomic position (correlates with indication). In a specific patient, the
      second homograft performs as well as the first.

PMID- 15953734
TI  - Prognostic factors in surgically resected N2 non-small cell lung cancer: the
      importance of patterns of mediastinal lymph nodes metastases.
AB  - OBJECTIVE: Patients with non-small cell lung cancer (NSCLC) with metastases to
      ipsilateral mediastinal lymph nodes (N2) are an heterogeneous group of patients
      as regard to prognosis and treatment. Indication and timing of surgery remain
      controversial. The present study investigates the prognostic factors, in order to
      identify homogenous subgroups of patients. METHODS: Histologically proven N2
      NSCLC patients, who underwent a complete surgical resection were retrospectively
      reviewed. Clinical and pathological features were reported and analyzed, and
      survival study was performed. RESULTS: One hundred eighty-three patients were
      analyzed. Overall 1.3 and 5 years survival rates were, respectively, 70, 35 and
      20%, with a median survival time of 24 months. Univariate analysis showed a
      significant better prognosis for: incidental N2 respect to clinical N2 (5-years
      35.4 vs 17.4%); single level lymph node involvement respect to multiple levels (5
      years 23.8 vs 14.7%); metastases to superior mediastinal or aortic nodes respect
      to lower mediastinal nodes (5-years 32 and 24.3 vs 16.3%); right upper lobe
      tumors with superior mediastinal nodes and left upper lobe tumors with aortic
      nodes respect to lower lobes tumors with lower mediastinal nodes (5-years 31.8
      and 26.9 vs 15.7%). Skip metastases had not a significant survival advantage
      respect to continuous lymphatic spread. N2 clinical status, the number of levels
      involved and the two specific patterns of lymphatic spread resulted significant
      prognostic factors at multivariate analysis. CONCLUSIONS: Clinical N2 status,
      number of lymph nodes levels involved and specific patterns of lymphatic spread
      identify homogenous subgroups of patients that can be proposed for different
      therapeutic strategies.

PMID- 15953735
TI  - Cutaneous dendritic cells.
AB  - Cutaneous dendritic cells (DC) include epidermal Langerhans cells (LC),
      interstitial/dermal dendritic cells (DDC), as well as plasmacytoid DC (pDC) that
      occur under pathological conditions. These immune cells have a spectrum of
      different functions with implications that extend far beyond the skin. They have
      the potential to internalize particulate agents and macromolecules, and display
      migratory properties that endow them with the unique capacity to journey between
      skin and draining lymph nodes where they encounter antigen-specific T
      lymphocytes. Herein, we will review the features of human and mouse cutaneous DC,
      emphasizing characteristics representative of their life-cycle stages that occur
      within the skin.

PMID- 15953736
TI  - Regulation of hippocampal synapse remodeling by epileptiform activity.
AB  - We examined the regulation of dendritic spines and synapses by epileptiform
      activity (EA) in rat hippocampal slice cultures. EA, which was induced by a
      GABA(A) receptor inhibitor, gabazine, reduced pyramidal neuron spine density by
      approximately 50% after 48 h and also caused an increase in the average length of
      remaining spines. To directly determine the effects of EA on synapses, we used
      fluorescent protein-tagged PSD95, which marks postsynaptic densities. EA induced
      a net loss of synapses on spines but not shafts; conversely, activity blockade
      (TTX) induced a loss of shaft synapses. Time-lapse confocal imaging in live
      tissue slices revealed that EA (1) shifts the balance of synapse gain and loss in
      dendrites leading to a net loss of spine synapses and (2) induces the formation
      of new filopodia-like dendritic structures having abnormally slow motility. These
      results identify EA-induced changes in the density and distribution of synaptic
      structures on dendrites.

PMID- 15953737
TI  - Phylogenetic relationships of the New World Troidini swallowtails (Lepidoptera:
      Papilionidae) based on COI, COII, and EF-1alpha genes.
AB  - A phylogeny of the Neotropical members of the Tribe Troidini (Lepidoptera:
      Papilionidae) was obtained with sequences of three protein-coding genes: two
      mitochondrial (COI and COII), and one nuclear (EF-1alpha). Parsimony and Bayesian
      analyses of 33 taxa resulted in very similar trees regardless of method used with
      the 27 troidines always forming a monophyletic clade. Within Troidini, the genus
      Battus is sister group to the remaining troidines, followed by a clade formed by
      the Paleotropical taxa (here represented by three exemplars). The genus Euryades
      is the next branch, and sister group of Parides. The genus Parides is
      monophyletic, and is divided into four main groups by Maximum Parsimony analysis,
      with the most basal group composed of tailed species restricted to SE Brazil.
      Character optimization of ecological and morphological traits over the phylogeny
      proposed for troidines indicated that the use of several species of Aristolochia
      is ancestral over the use of few or a single host-plant. For the other three
      characters, the ancestral states were the absence of long tails, forest as the
      primary habitat and oviposition solitary or in loose group of several eggs.

PMID- 15953738
TI  - Assessment of renal injury in vivo.
AB  - The ICH S7A (Safety Pharmacology for Human Pharmaceuticals) guidelines specify
      that potential adverse pharmacologic effects of a test substance on renal
      function should be evaluated in supplemental studies when there is a cause for
      concern (ICH, 2001). For the most part, this can easily be accomplished by
      examination of the appropriate analytes in urine and blood collected as part of
      the routine preclinical safety studies. This review will serve as an overview of
      the selection, interpretation and limitations of standard clinical pathology
      methods (serum chemistry and urinalysis) for assessment of renal function in such
      studies, as well as provide some information on emerging biomarkers of renal
      function.

PMID- 15953739
TI  - Evidence that erythrocytes are highly susceptible to exercise oxidative stress:
      FT-IR spectrometric studies at the molecular level.
AB  - We tested the hypothesis that usual exercise oxidative stress strongly affects
      erythrocytes viability. A 120-min physical exercise with progressive intensity
      was used as a model of oxidative stress. FT-IR spectrometry was used to determine
      structural changes in erythrocyte contents (phospholipids, proteins, lactate, and
      glucose) from blood samples taken every 20 min. Carbonyl formation from amino
      acid residues (P = 0.03) and hemoglobin unfolding (P = 0.01) could be identified
      as main protein denaturation markers during oxidative stress. Higher unsaturation
      level (P = 0.001) in phospholipids fatty acyl chains were also observed while
      VO(2) increased (P < 0.05). The increase in lactacidosis affected primarily
      hemoglobin unfolding (P = 0.02). Finally, two distinct cellular events occurred
      during oxidative stress: 1 - phospholipids peroxidation correlated to VO(2), but
      lactacidosis and hemoconcentration remained secondary factors; 2 - hemoglobin
      denaturation was mainly observed through unfolding and carbonylation, and
      lactacidosis and hemoconcentration were important contributing factors.

PMID- 15953740
TI  - Interpersonal and communication skills training for radiology trainees using a
      rotating peer supervision model (microteaching).

PMID- 15953741
TI  - Risk factors for cross-country horse falls at one-day events and at two-/three
      day events.
AB  - The cross-country phase of eventing competitions has been associated with
      injuries and fatalities to horses and riders. A case-control study was carried
      out to identify variables that were associated with increased or decreased risk
      of a horse fall on the cross-country phase at event competitions. After initial
      analysis, the dataset was split according to the categories of one-day events as
      compared to two- or three-day events to establish whether significant risk
      factors varied between the different types of eventing competitions. Data were
      collected for 121 cases (horse falls) at one-day events, 59 cases at two- or
      three-day events and for their 540 matched controls. The data were analysed using
      conditional logistic regression. The variables of no previous refusals on the
      course, fences with a landing in water and the combined variable of the angle and
      the spread of the fence were significantly associated with the risk of a horse
      fall in both datasets. Additional risk factors for one-day event falls were:
      fences requiring a take-off from water, a drop landing, the rider's knowledge of
      their position before the cross-country phase and if the rider received cross
      country tuition. Three-day event risk factors in the multivariable model
      included: the camber of the fence and participation in non-equestrian sports by
      the rider. This study identified variables that were significantly associated
      with an increase or a decrease in the risk of a horse fall during the cross
      country phase of different types of eventing competitions. Some of these
      variables are modifiable and the results of this study have been reported to the
      governing body of the sport of eventing in the UK so that possible interventions
      might be considered.

PMID- 15953742
TI  - Structural anisotropy and internal magnetic fields in trabecular bone: coupling
      solution and solid dipolar interactions.
AB  - We investigate the use of intermolecular multiple-quantum coherence to probe
      structural anisotropy in trabecular bone. Despite the low volume fraction of
      bone, the bone-water interface produces internal magnetic field gradients which
      modulate the dipolar field, depending on sample orientation, choice of dipolar
      correlation length, correlation gradient direction, and evolution time. For this
      system, the probing of internal magnetic field gradients in the liquid phase
      permits indirect measurements of the solid phase dipolar field. Our results
      suggest that measurements of volume-averaged signal intensity as a function of
      gradient strength and three orthogonal directions could be used to non-invasively
      measure the orientation of structures inside a sample or their degree of
      anisotropy. The system is modeled as having two phases, solid and liquid (bone
      and water), which differ in their magnetization density and magnetic
      susceptibility. A simple calculation using a priori knowledge of the material
      geometry and distribution of internal magnetic fields verifies the experimental
      measurements as a function of gradient strength, direction, and sample
      orientation.

PMID- 15953744
TI  - ADAM33: a newly identified protease involved in airway remodelling.
AB  - Asthma is a complex disorder in which major genetic and environmental factors
      interact to both initiate the disease and modify its progression. While asthma is
      recognised as a disorder of the conducting airways characterised by Th2-directed
      inflammation, it is being increasingly apparent that alteration of the structural
      cells of the airways (airway remodelling) is also fundamental to disease
      chronicity and severity. The gene ADAM33, encoding a novel member of a identified
      as an asthma susceptibility gene as the result of a positional cloning effort in
      a cohort of families recruited form the UK and USA. Subsequent genetic studies
      have now provided evidence that ADAM33 may be involved in determining lung
      function throughout life, associated with early life lung function as well as
      increased decline therapeutic intervention in asthma and future work will focus
      on the mechanisms by which it alters lung function and bronchial
      hyperresponsiveness.

PMID- 15953743
TI  - A randomized clinical trial of magnesium sulphate as a vehicle for nebulized
      salbutamol in the treatment of moderate to severe asthma attacks.
AB  - Although it is well known that intravenous administration of MgSO4 as an adjunct
      to conventional therapy is effective in treating asthma attacks, the effect of
      nebulized MgSO4 as a vehicle for salbutamol has been less evaluated. The aim of
      this study was to compare the effects of nebulized salbutamol administrated
      through either MgSO4 or isotonic saline solution on the 'peak expiratory flow
      rate' (PEFR), other respiratory and clinical parameters, and hospitalization rate
      of patients suffering from moderate to severe asthma attacks. Twenty-six patients
      with asthma attack were enrolled in the study in a randomized single blind
      fashion. After obtaining initial peak expiratory flow measurements (PEFR) and
      clinical evaluation, all patients received 1mg/kg corticosteroids and oxygen
      therapy and then either isotonic MgSO4 (2.5 ml, 6.3%)+salbutamol (2.5 ml) or
      saline (2.5 ml)+salbutamol (2.5 ml) through a jet nebulizer (group 1 (n=14) vs
      group 2 (n=12), respectively). The nebulizations were repeated every 20 min for
      the first hour and every hour for the rest of 4 h. The PEFR measurements and
      clinical assessment were performed after nebulization at 20th, 60th, 120th, 180th
      and 240th minutes. Patients were discharged when PEFR reached the target level of
      70% of predicted. The baseline PEFRs and clinical parameters were similar between
      groups 1 and 2 (50.2+/-18.5 vs 44.1+/-13.9, respectively, p>0.05). The mean%
      increase in PEFR at different measurement levels was similar between the groups.
      When the treatment response was evaluated within the groups, group 2 showed
      statistically significant increase in PEFR (% of predicted) 1h earlier than group
      1 (60th vs 120th minute, p=0.003 vs p=0.007). The mean duration of achieving
      target-PEFRs was 105.7+/-72.1 min for group 1 and 118.3+/-96.7 min for group 2
      (p>0.05). This study suggested that the additional usage of MgSO4 to nebulized
      salbutamol has no beneficial effect on the treatment of asthma attacks.

PMID- 15953745
TI  - Effects of caffeic acid phenethyl ester on lipopolysaccharide-induced lung injury
      in rats.
AB  - Extracts of propolis, a natural beehive product, have been known for centuries to
      have a variety of beneficial medical properties, among which their anti
      inflammatory effect is a major one. Caffeic acid phenethyl ester (CAPE), an
      active propolis component, has antimicrobial, anti-inflammatory, antioxidant,
      carcinostatic and immunomodulatory properties. In this study, we aimed to
      investigate the efficacy of CAPE in endotoxin-induced lung injury in rats. Lung
      injury was induced by a footpad injection of lipopolysaccharide (LPS). In the
      treatment group, 10 micromol kg(-1) CAPE was injected intraperitoneally
      immediately after LPS injection. At 24 h after LPS and/or CAPE injection, blood
      and lung tissue specimens were collected. MDA levels and MPO activity in serum
      and lung tissue, serum total antioxidant levels, lung tissue Na(+)/K(+) ATP-ase
      activity and histopathological evaluation were determined to assess the efficacy
      of CAPE treatment. CAPE was found to be efficient in reducing inflammation and
      lung tissue damage induced by LPS in rats.

PMID- 15953746
TI  - Intraspecific variation in gene expression after seawater transfer in gills of
      the euryhaline killifish Fundulus heteroclitus.
AB  - Previous research has suggested that northern populations of the euryhaline
      killifish (Fundulus heteroclitus) are better adapted to freshwater environments
      than their southern counterparts. In this study, we examined whether this
      adaptation has come at an ionoregulatory cost in seawater, by comparing published
      data for northern killifish to newly acquired data on the molecular responses of
      southern killifish to seawater transfer. After abrupt transfer from brackish
      water (10 per thousand) to seawater, Na,K-ATPase activity, Na,K-ATPase alpha(1a)
      mRNA expression, and NKCC1 mRNA expression increased 1 and 4 days after transfer
      in the gills of southern fish (by 2-3-fold), but increased at 1 day and not 4
      days after transfer in northern fish. Small increases in mRNA expression were
      observed in both populations at 14 days. CFTR expression also increased in
      southern and northern fish at 1 and 4 days into seawater, and was also elevated
      at 14 days in northern fish. Because fish from both southern and northern
      populations maintained plasma Na(+) and Cl(-) balance after seawater transfer,
      the differences in activity and expression could not have been caused by
      differences in plasma ion levels. Instead, some other regulatory factor may
      account for the differences in expression between populations. This study shows
      that freshwater adaptation in northern populations of killifish has not
      necessarily come at a significant ionoregulatory cost in seawater, but has
      altered the molecular responses of their gills to seawater transfer compared to
      southern killifish.

PMID- 15953747
TI  - The effect of temperature acclimation on myocardial beta-adrenoceptor density and
      ligand binding affinity in African catfish (Claris gariepinus).
AB  - This study assessed the effects of temperature acclimation on myocardial beta
      adrenoceptor density (B(max)) and binding affinity (K(d)) in African catfish
      (Claris gariepinus) acclimated to 15, 22 and 32 degrees C. B(max) values were not
      significantly different (P > 0.05) among the three acclimation groups.
      Conversely, the K(d) value of the 32 degrees C acclimation group (K(d) = 0.88)
      was significantly higher (P = 0.002) than both the 15 degrees C (K(d) = 0.48) and
      22 degrees C (K(d) = 0.46) acclimation groups. In addition, K(d) of rainbow trout
      (Oncorhynchus mykiss) was significantly lower (P < 0.001) and B(max)
      significantly higher (P < 0.05) than that of African catfish at all three
      acclimation temperatures. These results contrast with those reported previously
      for temperate species, in which B(max) is inversely related to acclimation
      temperature, and counter a previous suggestion that B(max) is higher in tropical
      versus temperate species.

PMID- 15953748
TI  - [Evolution of indications and consumptions of fresh frozen plasma from 1997 to
      2003 in a teaching Hospital].
AB  - OBJECTIVE: Study the evolution for 7 years of the distribution of fresh frozen
      plasma consumptions (FFP) according to the therapeutic indications. MATERIALS AND
      METHODS: Introduction in the software of the blood bank of a specific character
      during the distribution of all the homologous FFP allowing a selective sort of
      the consumptions of FFP according to their therapeutic indications. These
      "qualifying terms" are defined in function, not only of the French legal
      references (issued on 3 December 1991),--consumption coagulopathy--global or
      specific deficit in coagulation factor, but also according to the specificities
      of our health care institution (liver transplant--thrombotic microangiopathies-
      open heart surgery). RESULTS: During 7 years, the consumption of FFP trebled in
      our institution. The indications of the FFP are now mainly medical, its use in
      surgery dramatically decreased. The complications are not very frequent, most of
      them are slight allergic reactions. CONCLUSION: New therapies, molecules coming
      from the research, recombinant proteins or coming from the plasma fractionation
      will certainly modify the indications of the fresh plasma frozen in the coming
      years. The supervision of our practices remains essential.

PMID- 15953749
TI  - [Rhabdomyosarcoma of the salivary glands. Report of 3 cases].
AB  - Rhabdomyosarcoma of the salivary glands is rare. Tumours develop mostly in
      children and young patients but can be diagnosed in older people. We report three
      new cases in women 7, 14 and 75 years old. Tumefaction of the parotid region and
      facial paralysis were the principle clinical symptoms. Two patients underwent a
      total parotidectomy and radiotherapy. The third patient had a locally advanced
      tumour and received chemotherapy followed by radiotherapy. Loco-regional
      recurrence was observed in all cases and median survival was 12 months.
      Rhabdomyosarcoma of the salivary glands is locally aggressive. Treatments include
      surgery and radiotherapy. The role of chemotherapy remains to be discussed.

PMID- 15953750
TI  - Glaucoma: thinking in new ways-a role for autonomous axonal self-destruction and
      other compartmentalised processes?
AB  - Glaucoma is a common neurodegenerative disease that affects retinal ganglion
      cells (RGCs). Substantial effort is being expended to determine how RGCs die in
      glaucoma. As in other neurodegenerative diseases, the majority of effort focuses
      on characterising apoptotic self-destruct pathways. However, apoptosis is not the
      only self-destruct mechanism that may be activated in neurons. It is now known
      that neurons have distinct classes of self-destruct programme that are spatially
      compartmentalised. In addition to the well-described intracellular suicide
      machinery in the neuronal soma, responsible for apoptosis, there is another,
      molecularly distinct, self-destruct programme localised in the axon. Evidence
      also supports the existence of compartmentalised degeneration programmes in
      synapses and dendrites. RGCs are no exception to this. Recent data, from in vitro
      studies and from an inherited mouse model of glaucoma, suggest that molecularly
      distinct degenerative pathways underlie the destruction of RGC somata and RGC
      axons. In various neurodegenerative diseases, axons, dendrites and synapses often
      degenerate well before the cells die, and there is increasing evidence that this
      is important for the production of clinical symptoms and signs. We hypothesise
      that such compartmentalised and autonomous programmes are of critical importance
      in the pathophysiology of glaucoma, and we suggest that studies of these
      processes are essential for a complete understanding of this complex disease.

PMID- 15953751
TI  - The relationship beween posture and back muscle endurance in industrial workers
      with flexion-related low back pain.
AB  - This preliminary cross-sectional study was undertaken to determine if there were
      measurable relationships between posture, back muscle endurance and low back pain
      (LBP) in industrial workers with a reported history of flexion strain injury and
      flexion pain provocation. Clinical reports state that subjects with flexion pain
      disorders of the lumbar spine commonly adopt passive flexed postures such as
      slump sitting and present with associated dysfunction of the spinal postural
      stabilising musculature. However, to date there is little empirical evidence to
      support that patients with back pain, posture their spines differently than pain
      free subjects. Subjects included 21 healthy industrial workers and 24 industrial
      workers with flexion-provoked LBP. Lifestyle information, lumbo-pelvic posture in
      sitting, standing and lifting, and back muscle endurance were measured. LBP
      subjects had significantly reduced back muscle endurance (P < 0.01). LBP subjects
      sat with less hip flexion, (P = 0.05), suggesting increased posterior pelvic tilt
      in sitting. LBP subjects postured their spines significantly closer to their end
      of range lumbar flexion in 'usual' sitting than the healthy controls (P < 0.05).
      Correlations between increased time spent sitting, physical inactivity and poorer
      back muscle endurance were also identified. There were no significant differences
      found between the groups for the standing and lifting posture measures. These
      preliminary results support that a relationship may exist between flexed spinal
      postures, reduced back muscle endurance, physical inactivity and LBP in subjects
      with a history of flexion injury and pain.

PMID- 15953752
TI  - Regulation of meristem activity by chromatin remodelling.
AB  - The continuity and plasticity of plant development rely on the regulation of
      meristem activity in response to endogenous and environmental signals. Many plant
      development regulators involved in meristem function are transcription factors or
      signalling molecules. In the past few years, the role of chromatin remodelling in
      programming, maintaining or resetting specific gene expression profiles in
      subsequent cell generations has been shown to be crucial in plant development.
      Here, we summarize plant chromatin-remodelling factors required to regulate shoot
      apical meristem activity, particularly its maintenance during organogenesis and
      transitions between distinct developmental phases.

PMID- 15953753
TI  - Emerging MAP kinase pathways in plant stress signalling.
AB  - Mitogen-activated protein kinase (MAPK) pathways transfer information from
      sensors to cellular responses in all eukaryotes. A surprisingly large number of
      genes encoding MAPK pathway components have been uncovered by analysing model
      plant genomes, suggesting that MAPK cascades are abundant players of signal
      transduction. Recent investigations have confirmed major roles of defined MAPK
      pathways in development, cell proliferation and hormone physiology, as well as in
      biotic and abiotic stress signalling. Latest insights and findings are discussed
      in the context of novel MAPK pathways in plant stress signalling.

PMID- 15953754
TI  - Tracking multiple targets with multifocal attention.
AB  - Attention allows us to monitor objects or regions of visual space and select
      information from them for report or storage. Classical theories of attention
      assumed a single focus of selection but many everyday activities, such as video
      games, navigating busy intersections, or watching over children at a swimming
      pool, require attention to multiple regions of interest. Laboratory tracking
      tasks have indeed demonstrated the ability to track four or more targets
      simultaneously. Although the mechanisms by which attention maintains contact with
      several targets are not yet established, recent studies have identified several
      characteristics of the tracking process, including properties defining a
      'trackable' target, the maximum number of targets that can be tracked, and the
      hemifield independence of the tracking process. This research also has
      implications for computer vision, where there is a growing demand for multiple
      object tracking.

PMID- 15953755
TI  - Interval timing: memory, not a clock.
AB  - Anticipation of periodic events signalled by a time marker, or interval timing,
      has been explained by a separate pacemaker-counter clock. However, recent
      research has added support to an older idea: that memory strength can act as a
      clock. The way that memory strength decreases with time can be inferred from the
      properties of habituation, and the underlying process also provides a unified
      explanation for proportional timing, the Weber-law property and several other
      properties of interval timing.

PMID- 15953756
TI  - New approaches to demystifying insight.
AB  - After a person has become stuck on a problem, they sometimes achieve a clear and
      sudden solution through insight--the so-called Aha! experience. Because of its
      distinctive experience, the origins and characteristics of insight have received
      considerable attention historically in psychological research. However, despite
      considerable progress in characterizing insight, the underlying mechanisms remain
      mysterious. We argue that research on insight could be greatly advanced by
      supplementing traditional insight research, which depends on a few complex
      problems, with paradigms common in other domains of cognitive science. We
      describe a large set of mini-insight problems to which multiple methods can be
      applied, together with subjective reports to identify insight problem-solving.
      Behavioral priming and neuroimaging methods are providing evidence about what,
      where, and how neural activity occurs during insight. Such evidence constrains
      theories of component processes, and will help to demystify insight.

PMID- 15953757
TI  - Simulation, mirroring, and a different argument from error.

PMID- 15953759
TI  - Absorption spectrophotometric study of supramolecular complexation of [60]- and
      [70]fullerenes with 24,26-dimethoxy-25,27-dihydroxy calix[4]arene.
AB  - Supramolecular interactions of 24,26-dimethoxy-25,27-dihydroxy calix[4]arene (1)
      with [60]- and [70]fullerenes have been studied in only chloroform and in a
      ternary solvent mixture comprising of chloroform, ethyl alcohol and toluene by UV
      vis absorption spectrophotometric method. The experimental results are explained
      using the model that takes into account the interaction between electronic
      subsystems of 1 and fullerene. The most interesting feature is the preference of
      [60]fullerene over [70]fullerene for 1 in ternary solvent mixture as revealed by
      higher value of formation constant of [60]fullerene/1 complex. The selectivity
      towards [60]fullerene opens up the way toward self-assembling systems and new
      separation and purification methods for fullerenes.

PMID- 15953760
TI  - Gas-solid reactions of single crystals: a study of reactions of NH3 and NO2 with
      single crystalline organic substrates by infrared microspectroscopy.
AB  - Reaction of single crystals of benzoic and trans-cinnamic acids with 200 Torr
      pressure of ammonia gas in a sealed glass bulb at 20 degrees C generates the
      corresponding ammonium salts; there is no sign of any 1:2 adduct as has been
      reported previously for related systems. Isotopic substitution using ND3 has been
      used to aid identification of the products. Adipic acid likewise reacts with NH3
      gas to form a product in which ammonium salts are formed at both carboxylic acid
      groups. Reaction of 0.5 Torr pressure of NO2 gas with single crystals of 9
      methylanthracene and 9-anthracenemethanol in a flow system generates nitrated
      products where the nitro group appears to be attached at the 10-position, i.e.
      the position trans to the methyl or methoxy substituent on the central ring.
      Isotopic substitution using 15NO2 has been used to confirm the identity of the
      bands arising from the coordinated NO2 group. The products formed when single
      crystals of hydantoin are reacted with NO2 gas under similar conditions depend on
      the temperature of the reaction. At 20 degrees C, a nitrated product is formed,
      but at 65 degrees C this gives way to a product containing no nitro groups. The
      findings show the general applicability of infrared microspectroscopy to a study
      of gas-solid reactions of organic single crystals.

PMID- 15953761
TI  - Vibrational spectral studies of L-citrullinium perchlorate.
AB  - Infrared and Raman spectra of L-citrullinium perchlorate crystals have been
      recorded at room temperature. The vibrational assignments of the observed
      wavenumbers are proposed on the basis of group theoretical analysis. The presence
      of carbonyl group indicates that the molecule exists in the ionic form. The
      shifting of stretching and bending wavenumbers indicates the presence of
      extensive hydrogen bonding in the crystal. The anion fundamentals however
      continue to be degenerated. This suggests that its symmetry is not affected in
      the crystal.

PMID- 15953762
TI  - Line shapes in CP/MAS (13)C NMR spectra of cellulose I.
AB  - The CP/MAS (13)C NMR line shape of cellulose I has been qualitatively analyzed by
      direct simulations using the Ornstein-Uhlenbeck stochastic process and the Kubo
      model. Both approaches describe a anhydroglucose C4 carbon as a oscillator with
      fluctuating Larmor frequency. The NMR resonance frequency is written omega=omega
      +omega(t), where the fluctuating part with zero mean was modelled as a stationary
      Markov diffusion process. The simulation results both motivates the use of
      multiple line shapes when fitting CP/MAS (13)C NMR spectra recorded on cellulose
      I and gives some insights into why signals from crystalline cellulose I give rise
      to Lorentzian line shapes.

PMID- 15953763
TI  - Terminal group effects on the fluorescence spectra of Eu(III) nitrate complexes
      with a family of amide-based 1,10-phenanthroline derivatives.
AB  - Four ligands 1,10-phenanthroline-5,6-bis(N,N-dibenzyl-1'-oxopropylamide) (La)
      1,10-phenanthroline-5,6-bis(N-methyl-N-benzyl-1'-oxopropylamide) (Lb) 1,10
      phenanthroline-5,6-bis(N-benzyl-1'-oxopropylamide) (Lc) and 1,10-phenanthroline
      5,6-bis(N,N-diethyl-1'-oxopropylamide) (Ld), and their lanthanide(III) (La and
      Eu) complexes were synthesized. The complexes were characterized by elemental
      analysis, IR, fluorescence spectroscopy and conductivity. The lanthanide atoms
      are coordinated by O atoms from C=O, Ar-O -C and N atoms from phen With the
      difference of the ligands, the fluorescent intensities of the Eu(III) complexes
      vary regularly in the THF solution. Some factors that influence the fluorescent
      intensity were discussed.

PMID- 15953764
TI  - Platelet apheresis affects prothrombin time and plasminogen levels in healthy
      donors.
AB  - There are few studies evaluating whether platelet apheresis has an effect on
      hemostasis parameters or not. The aim of this study was to define the effects of
      platelet apheresis on hemostasis screening tests and plasminogen levels. The
      study was performed on 40 healthy donors. We compared the values obtained before
      and after apheresis and observed that the prothombin time (PT) elongated,
      plasminogen levels decreased and the activated partial thromboplastin and
      thrombin times were not changed significantly. The differences were not high
      enough to cause any hemostasis problem. It can be hypothesized that platelet
      apheresis affects PT and plasminogen levels in healthy donors.

PMID- 15953765
TI  - Capillary electrophoresis for monitoring the effects of plasmapheresis: a
      feasibility study.
AB  - Plasmapheresis is an established method to treat patients with large monoclonal
      gammopathies (M-components) that increases the blood viscosity. During
      plasmapheresis the patient plasma is substituted with a mixture of saline,
      albumin and normal plasma. The treatment results in a reduction of the M
      component in the circulation. Plasmapheresis causes changes in several proteins,
      which makes monitoring by nephelometric or turbidimetric analysis of specific
      proteins less suitable. Quantification of paraproteins by nephelometric assays
      are also known to be associated with technical problems. An alternative could be
      agarose gel electrophoresis but this method is too slow to permit monitoring
      during the plasmapheresis. Capillary electrophoresis of plasma proteins can be
      performed in less than 10 min. We have used the CAPILLARYS capillary
      electrophoresis system (Sebia, Paris, France) to monitor the effect of
      plasmapheresis treatment on 22 occasions. The mean reduction in M-component size
      was 51%, range 33-61%. Capillary electrophoresis is a rapid and inexpensive
      method that could be used to monitor the effect of plasmapheresis during the
      actual treatment.

PMID- 15953766
TI  - Targeted delivery of oligodeoxynucleotides to mouse lung endothelial cells in
      vitro and in vivo.
AB  - Pulmonary endothelium plays an important role in the maintenance of normal
      pulmonary physiology and its dysfunction is involved in a number of pulmonary
      diseases. Correction of endothelial dysfunction via antisense
      oligodeoxynucleotides (ODN) is dependent on the development of a delivery vehicle
      that can efficiently deliver the ODN to pulmonary endothelium with minimal
      toxicity. To this end, we have developed a novel lipidic vector that is highly
      efficient in targeted delivery of ODN to pulmonary endothelium. This is based on
      a method that utilizes an ionizable aminolipid (1,2-dioleoyl-3-dimethylammonium
      propane) and an ethanol-containing buffer system for encapsulating large
      quantities of polyanionic ODN in lipid vesicles. An endothelium-specific antibody
      (273-34A) is incorporated into the lipid vesicles via a
      distearoylphosphatidylethanolamine-poly(ethylene glycol) spacer. The 273-34A
      antibody efficiently mediated delivery of ODN to mouse lung endothelial cells in
      vitro and in vivo. Furthermore, systemic administration of this formulation is
      associated with minimal hematological toxicities and induces little acute change
      in systemic and pulmonary hemodynamics. These results provide a basis for lipid
      mediated delivery of ODN for the treatment of pulmonary diseases. They also
      suggest the utility of this approach as a research tool to characterize the
      function of genes in the pulmonary endothelium.

PMID- 15953767
TI  - Small hairpin RNAs efficiently inhibit hepatitis C IRES-mediated gene expression
      in human tissue culture cells and a mouse model.
AB  - Treatment and prevention of hepatitis C virus (HCV) infections remain a major
      challenge for controlling this worldwide health problem; existing therapies are
      only partially effective and no vaccine is currently available. RNA interference
      offers the potential of a novel therapeutic approach for treating HCV infections.
      Toward this end, we evaluated small hairpin interfering RNAs (shRNAs) targeting
      the conserved internal ribosome entry site (IRES) element of the HCV genome for
      their ability to control gene expression in human cells and animals. We used a
      reporter gene plasmid in which firefly luciferase (fLuc) expression is dependent
      on the HCV IRES. Direct delivery of HCV IRES shRNAs efficiently blocked HCV IRES
      mediated fLuc expression in transfected human 293FT cells as well as in a mouse
      model in which nucleic acids were delivered to liver cells by hydrodynamic
      transfection via the tail vein. These results indicate that shRNAs, delivered as
      RNA or expressed from viral or nonviral vectors, may be effective agents for the
      control of HCV and related viruses.

PMID- 15953768
TI  - Administration route- and immune cell activation-dependent tumor eradication by
      IL12 electrotransfer.
AB  - Injection of DNA via electric pulses into targeted tissues is referred to as
      electrotransfer. Intratumoral electrotransfer of the IL12 gene is more effective
      than intramuscular electrotransfer of the same gene in the eradication of
      established tumors. To understand the underlying immunological mechanisms, T cell
      infiltration, CTL activity, inhibition of angiogenesis, and transgene expression
      were analyzed using immunohistochemistry, fluorescence-based CTL analysis,
      Northern blot, and ELISA. In addition, the therapeutic effects of IL12 gene
      therapy were determined in immunocompetent, immune-cell-depleted, and
      immunodeficient mice. We found that intratumoral, but not intramuscular,
      electrotransfer of the IL12 gene induces CD8+ T cell infiltration, CTL activity,
      and tumor eradication. Tumor eradication by intratumoral IL12 gene
      electrotransfer requires both NK and T cells. The absence of either cell type
      will abrogate the intratumoral IL12 gene therapy-induced tumor eradication. Such
      a requirement explains why tumors cannot be eradicated by intramuscular
      electrotransfer of the IL12 gene. Only NK-cell-dependent, and not T-cell
      dependent, anti-tumor effects are induced by intramuscular administration.
      Together, these results suggest that NK cells play an important role in both
      administration routes, mediating tumor growth inhibition, but T cells are
      specifically activated by intratumoral IL12 gene electrotransfer and not by the
      intramuscular route.

PMID- 15953769
TI  - Anticonvulsant effects of the wasp Polybia ignobilis venom on chemically induced
      seizures and action on GABA and glutamate receptors.
AB  - Venoms of spiders and wasps are well recognized to present high affinity to the
      central nervous tissue of many mammalian species. Here we describe the effects of
      direct exposure of rat (Rattus norvegicus) brains to the crude and denatured
      venom of the Brazilian social wasp Polybia ignobilis. Lower doses of crude venom
      injected via intracerebroventricular (i.c.v.) inhibited the exploratory activity
      of animals, while higher doses provoked severe generalized tonic-clonic seizures,
      with hind limb extension. The status epilepticus lasted for few minutes leading
      the animals to respiratory depression and death. In contrast, the denatured venom
      was anticonvulsant against acute seizures induced by the i.c.v. injection of
      bicuculline, picrotoxin and kainic acid, but it was ineffective against seizures
      caused by systemic pentylenetetrazole. Moreover, the [3H]-glutamate binding in
      membranes from rat brain cortex was inhibited by the denatured venom in lower
      concentrations than the [3H]-GABA binding. The denatured venom contains free GABA
      and glutamate (34 and 802 pg/microg of venom, respectively), but they are not the
      major binding inhibitors. These interactions of venom components with GABA and
      glutamate receptors could be responsible for the anticonvulsant effects
      introducing the venom from P. ignobilis as a potential pharmacological source of
      anticonvulsant drugs.

PMID- 15953770
TI  - Alteration in endothelial function and modulation by treatment with pioglitazone
      in rabbit renal artery from short-term hypercholesterolemia.
AB  - The present study was undertaken to investigate endothelial function and
      epoxyeicosatrienoic acids (EETs), which is a cytochrome P-450 monooxygenase (CYP)
      metabolite and one of the candidates as an endothelium-derived hyperpolarizing
      factor (EDHF) in the renal artery isolated from short-term hypercholesterolemic
      rabbits, and also to characterize the effects of pioglitazone on it. Rabbits were
      fed normal, 0.5% cholesterol chow, or 0.5% cholesterol chow plus 300 ppm
      pioglitazone for 5 weeks. The tension of isolated renal artery rings was measured
      isometrically. Serum lipid levels were measured and morphometric analysis was
      performed. EET contents in the renal artery were also determined. The cholesterol
      chow diet for 5 weeks increased serum lipid levels, and pioglitazone had no
      influence on it. In the phenylephrine precontracted renal artery, the cholesterol
      chow did not affect acetylcholine-induced relaxation. The N(G)-nitro-l-arginine-
      and indomethacin-resistant endothelium-dependent relaxation induced by
      acetylcholine was significantly enhanced in rabbits receiving the cholesterol
      chow as compared to rabbits receiving the control diet, and pioglitazone
      normalized it. The resistant part of acetylcholine-induced relaxation was
      significantly inhibited when the renal artery was treated with charybdotoxin, an
      inhibitor of large- and intermediate-conductance Ca(2+)-activated K(+) channels,
      or N,N-di-ethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF 525a), a
      nonselective CYP inhibitor, and it was significantly inhibited by sulfaphenazole,
      a selective CYP2C9 inhibitor in rabbits receiving only the cholesterol chow. In
      KCl-precontracted renal artery, the cholesterol chow inhibited acetylcholine
      induced relaxation and pioglitazone normalized it. The cholesterol chow increased
      the production of EETs and reduced nitrate/nitrite contents in the renal artery,
      and pioglitazone strongly suppressed them. These results suggest that the EETs
      may be one of the EDHFs in the rabbit renal artery and beneficial effects of
      pioglitazone on alterations in endothelial function induced by cholesterol
      feeding are due, in part, to the protective action on the nitric oxide system
      and/or the suppression of increased production of EETs.

PMID- 15953772
TI  - Overexpression and preliminary X-ray crystallographic analysis of
      prophenoloxidase activating factor II, a clip domain family of serine proteases.
AB  - A clip domain family of serine proteases has been identified in invertebrates as
      a crucial enzyme involved in diverse biological processes including immune
      responses and embryonic development. Although these proteins contain at least one
      clip domain at the N-terminal of the serine protease domain, the roles and three
      dimensional structure of the clip domain are unknown. Prophenoloxidase activating
      factor-II (PPAF-II), a clip domain family of serine proteases, derived from the
      beetle Holotrichia diomphalia larvae, was overexpressed in the baculovirus
      system, and crystallized using the hanging-drop vapor-diffusion method. High
      quality single crystals of PPAF-II were obtained in a precipitant solution
      containing 0.15 M ammonium sulfate, 1.25 M lithium sulfate monohydrate, and 0.1 M
      sodium citrate dehydrate (pH 5.5). These crystals belong to space group C2 with
      unit-cell parameters a=107.84, b=76.78, c=70.49 A and beta=113.93 degrees , and
      contain one or two molecules in the asymmetric unit. Determination of the three
      dimensional structure of PPAF-II would clarify the functions of the clip domains.

PMID- 15953771
TI  - Crystallization of three key glycolytic enzymes of the opportunistic pathogen
      Cryptosporidium parvum.
AB  - Cryptosporidium parvum is one of the major causes of waterborne diseases
      worldwide. This protozoan parasite depends mainly on the anaerobic oxidation of
      glucose for energy production. In order to identify the differences in the three
      dimensional structure of key glycolytic enzymes of C. parvum and its human host,
      we have expressed, purified and crystallized recombinant versions of three
      important glycolytic enzymes of the parasite, namely, glyceraldehyde 3-phosphate
      dehydrogenase, pyruvate kinase and lactate dehydrogenase. Lactate dehydrogenase
      has been crystallized in the absence and in the presence of its substrates and
      cofactors, while pyruvate kinase and glyceraldehyde 3-phosphate dehydrogenase
      were crystallized only in the apo-form. X-ray diffraction data have been
      collected for all crystals.

PMID- 15953774
TI  - What grounds creativity?
AB  - "Developmental or ordinary creativity" is distinguished from "genius creativity."
      The former offers pleasure or distraction. The latter sometimes offers this, but
      tarrying before the product of genius also brings a new understanding of one's
      culture, one's self, and even an experience of transcendence. The concepts of
      Heidegger and of Gadamer are applied to this distinction. All serious artists are
      seen as manifesting one or more of three aspects: (1) driven by creative genius
      from the biological furnace of the individual, (2) temporary regressions and
      exhaustion of ego function, and (3) an anxiety-driven process resting on a
      constitutional ability to shift levels of ego activities and compromise
      formations. Falling in love is discussed as another example of creative
      imagination based on the need to solve psychological discomfort either due to
      developmental or pathological problems. Creativity in psychoanalytic work is an
      important factor that needs to be explored in addition to the fact that every
      country seems to create the approach to psychoanalysis that it needs. Emotional
      illness is demonstrated as hindering and constricting creativity, not enhancing
      it as is the popular idea. Some seriously psychopathological artists are able to
      wall off the pathology and sublimate their conflicts into the production of art,
      but creativity requires a relatively intact ego; when the ego deteriorates, so
      does the creative product. An important spring to genius creativity is the
      nonrecognition of the extremely talented child, which leads to solitary activity
      and an immersion in ideas and fantasies that, if the person has the requisite
      talent, is manifested in the expression of truth and beauty through art.

PMID- 15953775
TI  - Degas's sculptures--three-dimensionality and action.
AB  - The psychological self is formed largely by the steady accretion of forms of
      organizing experience. Outside of the interpersonal realm, these formal and
      categorical modes of organization can be incorporated through cyclical,
      continuous, and episodic interaction with modes of cultural expression, such as
      art, music, and poetry. Degas's sculptures, a highly experimental and personal
      section of his overall work, have particular formal modes of organization unique
      to this artist and to his particular era. Formal principles unique to Degas
      sculpture include the ways he rendered sculpted surfaces, masses in a state of
      action, and uniquely collaged materials. Degas's sculptures are proto-cinematic
      because they depict a brief instant in time, as opposed to a more prolonged
      narrative episode. Empathic, though unconscious, identification with the formal
      principles of Degas's sculptures shapes in the viewers ordering principles in the
      self that govern reactions to the vicissitudes of living, object relations, the
      sense of mortality, and the accomplishment of a sense of agency significant and
      consequential to the modern era.

PMID- 15953776
TI  - Images of trauma: pain, recognition, and disavowal in the works of Frida Kahlo
      and Francis Bacon.
AB  - The role of art in the encounter with trauma and destructiveness is comparatively
      studied in the works of Frida Kahlo and Francis Bacon as examples of a direct and
      a more indirect way of dealing with such experiences. A creative product may
      function intrapsychically as a kind of messenger between dissociated self-states
      and consciousness, and it may also serve as a witnessing presence in a self
      supporting and self-constituting way. Artistic work may thus be used by the
      artist for an expressive as well as for a protective purpose, as a means of
      sympathetic participation in painful experience, or as a medium for a view from
      the outside. The act itself of finding and of making expressive forms at the time
      of traumatic experience is a remarkable assertion of the human capability to
      synthesize and to counteract fragmenting dissociative processes.

PMID- 15953777
TI  - Consulting to Star Trek: to boldly go into dynamic neuropsychiatry.
AB  - Technical consultation to a screenwriter of episodes for The Next Generation,
      Deep Space Nine, and Voyager series of Star Trek drew upon the new discipline of
      dynamic neuropsychiatry to originate ideas for the alien experiences in the
      science fiction scripts. In particular, the neurologic misidentification
      syndromes, which elicit complex neuropsychic defenses and illustrate the
      psychodynamics of object relations, provided a sense of strangeness. The wide,
      creepy popular appeal of the syndromes, described here, reveals a latent mental
      defensive structure that is activated by psychopathology and neuropathology, but
      that is also somehow sensed by those who are more or less neurologically intact.
      Illustrative examples are drawn from these series and the more recent Enterprise
      series that has been aired since the consultation. In addition, the changing
      persona of the physician character in Star Trek is a projection of our changing
      status in American society.

PMID- 15953778
TI  - A psychoanalytic consideration of Pasolini's Salo.
AB  - Salo represented the culmination of Pier Paolo Pasolini's career as a filmmaker
      and engages several questions concerning the nature of perversion and the
      excitement with the negative. Through exploration of Pasolini's motives and
      techniques for creating this film, an analysis is offered of the creative process
      that does not seek to create an aesthetically pleasing compromise formation of
      psychic conflict, nor a form of erotizing sadomasochism. Rather, this film is
      explored as an example of a lucid and psychoanalytically informed artwork that
      speaks to the psychic fascination with what is purely negative--thanatos--which
      is not mediated by libido.

PMID- 15953779
TI  - The musician and the creative process.
AB  - Music is the embodiment through sound of lived experience. Conscious and
      unconscious modes of subjectivity are woven together in a tapestry of tone and
      sound, which is less about the world and more the symbolic equivalent of human
      subjectivity itself. Musicians through their interpretation of a composition
      invests their performance with self experience, and they come to experience
      themselves as vibrantly mirrored in the ideal form of the music. In other words,
      the musical performance is an opportunity for selfobject experience. Musical
      performance involves a two-phase process. The first is the practice phase, during
      which the musician seeks to achieve the experience of aesthetic resonance in
      which self-experience and music are brought into sync through the perfection of
      the performance. The dynamic role of selfobject failure and restoration in the
      musician's motivation to perfect the performance is stressed. The second phase is
      the public performance, during which the musician exhibits his or her ideal
      creation and experiences the mirroring of the audience. During these phases,
      there is a creative dialectic between internal and externalized aspects of self
      experience. An examination of case material from analytic work with a musician
      shows how an inhibition in the creative process may be based on the expectation
      of selfobject failure, and how musical creativity can be facilitated through new
      opportunities for selfobject experience in the transference.

PMID- 15953780
TI  - Psychoanalysis, creativity, and hope: forward edge strivings in the life and work
      of choreographer Paul Taylor.
AB  - Psychoanalysis and creativity are not interchangeable enterprises; however, both
      creativity and psychoanalysis promise the hope of transformation. But hope may be
      fragile. Healthy aspects of self may hide and diminish hope to protect it against
      invasion from toxic pathological patterns. Hope may be rekindled by an
      empathically responsive environment and the reengagement of healthy forward edge
      strivings. Psychoanalysis illustrates creativity as a conduit for hope. Modern
      dance choreographer Paul Taylor's 1988 autobiography, Private Domain, describes
      Taylor's hope and strivings through creative engagement. Unfortunately, when
      Taylor's body inevitably falters after years of performing, he is unprepared
      psychologically to cope successfully. Taylor's sense of self begins to fragment
      and his forward edge strivings to decay. Eventually, Taylor collapses on stage
      from drug addiction and illness; his performing career crashes to an end. Taylor
      must search for his forward edge strivings with hope. Psychoanalysis illuminates
      Taylor's journey to find hope, motivation, meaningful intention, and
      transformation through creativity and dance-making.

PMID- 15953781
TI  - The contributions of Marcel Proust to psychoanalysis.
AB  - This article is about the major contribution of Marcel Proust to psychoanalysis
      in his seven-part novel, A La Recherche Du Temps Perdu (translated as Rembrance
      of Things Past, 1934). This work spans two decades, from 1988, when Proust
      writing to 1927, when the last part was published 5 years after his death.
      Proust, a literary scholar whose knowledge dated to the early Greeks, knew
      nothing of Freud or psychoanalysis. His major contributions were to the emergence
      of memory, specifically the exquisite details of the descriptive unconscious,
      which we can now explain in cognitive neuroscientific terms. Freud wanted to do
      this for all mental processes in 'The Project'. Proust contributed to the
      projective aspects of passionate love. Kernberg has pointed out that although
      psychoanalysts knew about transference love, idealization, and sex, love has only
      been a subject for us in the 1900s. Proust also wrote of jealousy as a necessary
      concomitant of love. He proposed that all humans had pluripotential sexuality and
      recognized the psychodynamics of the perversions in a way that is closer to
      modern psychoanalysts like Chassuguet-Smirgel. Proust was himself psychologically
      disabled, with an illness his father called neurasthenia, adding somatic
      components and abulia, inability to make decisions. We would probably recognize
      him today as having a borderline personality disorder, with superior cognition,
      depression, somatization, obsessions, compulsions, phobias, and severe anxiety,
      which he understood was the result of his inability to separate from his mother.
      Proust's findings in all these areas are compared with the psychoanalytic
      literature--Freud, to the present.

PMID- 15953782
TI  - Erich Fromm's productivity: creativity as exemplified by Joyce's blooming of
      Leopold and Molly.
AB  - According to Erich Fromm, the productive character expresses what he called the
      life force in ways that are, by nature, artistic in quality. His valuing of the
      vital and the artistic, fueled by this life force in our potential to be human,
      serves as the cornerstone of his model of psychoanalysis. Gilbert Rose, author of
      Necessary Illusion: Art as "Witness", also has identified the parallel between
      analytic and artistic processes, building on the assumption that the therapeutic
      alliance and the aesthetic alliance are one and the same. In elaborating this
      assumption and extending the parallel between Rose and Fromm, I draw the
      conclusion that the qualities of relationships have an impact on one's ability to
      express oneself creatively, to live an artistic life--that is, to live
      productively. Psychoanalysis is, in practice, a process that is artistic,
      creative, and re-creative in nature. To the degree that authentic expression of
      emotionally charged implicit knowledge of the ineffable (the emotional life that
      resides deep in the bodymind) results in transformation and healing, the process
      is artistic in nature. This process is exemplified by examining the life and
      literary creations of James Joyce, especially Joyce's characters of Molly and
      Leopold Bloom in Ulysses.

PMID- 15953783
TI  - An attempt at unmasking Eugene O'Neill.
AB  - Masks appear in several of Eugene O'Neill's early plays, serving not as a mere
      technical innovation, but rather as a way to explore "hidden conflicts" of human
      nature. This article explores three factors that could have provoked this
      sensitivity to the motif of masking. First is the influence of Greek tragedy-
      itself a domain of "the masked God"--which O'Neill tried to restore through
      several of his plays. Second is O'Neill's insight into the connection between
      modern man's selfhood and the process of masking, several decades before
      psychoanalysts have approached it scientifically, in complete accordance with
      Kohut's hypothesis about the "anticipatory function of art". The final factor
      consists of both his early development and his later life--especially his three
      marriages--as revealed through extensive biographies, correspondence, and plays.
      The article suggests that the most important influence on O'Neill's sensitivity
      to motif of masking was his mother's morphine addiction.

PMID- 15953784
TI  - Federico Garcia Lorca's Yerma: the use of a vitalizing fantasy self-object to
      survive trauma.
AB  - Federico Garcia Lorca, one of the 20th century's greatest playwrights, wrote his
      masterpiece, Yerma, shortly after feeling betrayed and abandoned by his closest
      friend Salvador Dali. At the same time, he also wrote a poem entitled "When I was
      Ten" that captured the pain and loneliness he experienced when his family moved
      from the country, where he was happy and surrounded by loving and admiring
      friends and family, to the city, where he was lonely and ridiculed in school for
      his effeminate manner. This temporal association suggests that Lorca was
      struggling with the same painful affects in adulthood as he had as a child and
      that he was employing the same coping mechanism he had developed early in his
      life, that of creating a fantasy that served as a secondary self-object to repair
      self-fragmentation caused by a rupture in a crucial primary self-object
      relationship. Through the creation of a play in which different characters give
      expression to the wide range of conflicting emotions that resulted from the self
      object rupture and the ensuing self-fragmentation, the playwright found a
      narrative that could contain them all and provide reparative self-cohesion.

PMID- 15953785
TI  - Listening to Oedipus: two poems by sons about fathers.
AB  - Using the writings of Thomas Ogden, Donald Spence, Jessica Benjamin, Roy Schafer,
      Evelyn Schwaber, and others, the author discusses the "kinship" between poets and
      psychoanalysts. The author also attempts to demonstrate how reading and listening
      to poetry can greatly enhance analytic listening, as well as illuminate how
      language that is contained within a guiding structure, such as a poem or an
      analysis, can "surprise" us into new awareness and meaning. Two poems are chosen,
      in which the speakers describe their relationships with their fathers in order to
      evoke oedipal associations. A brief discussion follows of how contemporary
      analysts are using intersubjective and relational lenses in order to expand on
      and revise traditional oedipal metaphor and theory and capture new levels of
      meaning. Each poem is then analyzed to underline how the sounds and selection, as
      well as sense of language, reveal the speaker's inner world and process. Poetry
      provides a mirror for the increasing richness, scope, and dialectical play that
      can be found in contemporary psychoanalysis.

PMID- 15953786
TI  - The artifice of literary dreams.
AB  - When it comes to interpreting dreams, literary critics have a distinct advantage,
      it would appear, over practicing analysts. Readers would assume that storytellers
      have crafted dreams in fictions to illuminate their characters and have provided
      the elements that analysts must struggle to collect and select: especially the
      day residue, the larger contextual associations, and an overarching narrative.
      The dream of a 23-year old woman from Ellen Glasgow's 1925 novel, Barren Ground,
      should illustrate the critic's advantage. Consideration, however, of the larger
      context, shrouded associations, and multiple master narratives (formulated by
      Freud, Jung, and Kohut) that the critic can profitably employ in understanding
      the young woman's dream raises fundamental questions about the critic's presumed
      advantage.

PMID- 15953787
TI  - Tools, works of art, psychoanalysis.
AB  - The roots of psychoanalysis lie deep within the evolutionary history of human
      life and intelligence. In this article I will explore a set of evolving
      relationships between human beings and the artifacts they have created. The
      psychoanalytic treatment method is one such artifact, despite the apparent
      reluctance of many psychoanalysts to describe what they do in terms that might be
      interpreted to minimize the personal element in their work with their patients.
      But the personal element can be effectively understood only through the study of
      individual human beings interacting with their surroundings. Psychoanalysis is a
      lineal descendent of simpler and earlier interactions with a special group of
      artifacts, those that incorporate human meanings in a way that provides a
      continuous source of feedback information.

PMID- 15953788
TI  - The victorian ethos of evolution.
AB  - The Victorian Age was the culmination of changes in the political, social,
      scientific, theological and cultural spheres throughout Europe. Darwin's newly
      elaborated evolutionary idea was the pivot for social Darwinism, a theory based
      on the gradual movement of the species toward greater self-awareness and
      strength. Shaw described this process in his play Man and Superman. Freud also
      utilized the concept in his libido theory. Horney interpreted the process as a
      psychic response to the intense societal pressures to succeed. A linkage of
      interdependence and progression of these ideas emerges as the world continues to
      evolve.

PMID- 15953789
TI  - EPILOGUE: creativity and polysemy--on the limits of pathography, psychobiography
      and art criticism.

PMID- 15953790
TI  - Nectar-secreting floral stomata in Maxillaria anceps Ames & C. Schweinf.
      (Orchidaceae).
AB  - BACKGROUND AND AIMS: Although it was generally assumed that Maxillaria spp. do
      not produce nectar, in recent years, nectar has been reported for a number of
      these orchids. Nevertheless, our current understanding of nectary structure and
      nectar secretion in Maxillaria is based solely on M. coccinea (Jacq.) L.O.
      Williams ex Hodge, which, since it shows many features characteristic of
      ornithophilous flowers, is atypical of this largely entomophilous genus. The aim
      of the present paper is to describe, for the first time, nectar secretion in a
      presumed entomophilous species of Maxillaria. METHODS: The structure of the
      nectary of M. anceps Ames & C. Schweinf., nectar composition and the process of
      nectar secretion were investigated using light microscopy, scanning electron
      microscopy, transmission electron microscopy, histochemistry, refractometry and
      high performance liquid chromatography. KEY RESULTS AND CONCLUSIONS: Nectar
      appears as droplets that are exuded by modified stomata borne upon the labellar
      callus and collects upon the labellum and at the base of the column-foot.
      Although such stomata are known to occur in a number of angiosperm families, this
      is the first time for them to be observed in orchids. The callus consists largely
      of parenchyma with raphides and is supplied by eight to ten collateral bundles.
      This tissue, together with the single-layered epidermis, seemingly contains
      terpenoids. During the bud stage, the callus cells contain an organelle
      complement consistent with secretory cells whereas by day 4 of anthesis, much of
      the cell is occupied by a vacuole. The nectar is sucrose-dominant but also
      contains low concentrations of glucose, fructose, free amino acids and possibly
      terpenoids. The high sugar concentration (approx. 66 %) is consistent with
      melittophily and may indicate that, like the majority of Maxillaria spp., M.
      anceps is visited by stingless bees (Meliponini).

PMID- 15953792
TI  - The clinical impact of negative psychological states: expanding the spectrum of
      risk for coronary artery disease.
AB  - OBJECTIVES: Research has demonstrated a gradient relationship between depression
      and the risk of adverse cardiovascular events among both initially healthy
      individuals and those with known cardiac disease. Moreover, recent investigators
      have demonstrated that adverse outcomes are even associated with the presence of
      relatively mild symptoms, as measured by self-report scales like the Beck
      Depression Inventory. The association between even mild depressive symptoms and
      sequelae of cardiac disease raises the following question: Is the spectrum of
      psychological factors associated with cardiac disease greater than previously
      recognized? METHODS: To address this issue, we consider a small but emerging
      literature that has focused on effects of other negative psychologic states on
      cardiovascular health. RESULTS: Five negative states that have been linked in
      varying degrees to cardiovascular disease or disturbances are identified,
      including hopelessness, pessimism, rumination, anxiety, and anger. Considering a
      broader spectrum of risk may help to understand more fully the mechanisms by
      which depression and other negative affective states influence coronary heart
      disease risk.

PMID- 15953793
TI  - Gender differences in the link between depression and cardiovascular disease.
AB  - OBJECTIVES: Cardiovascular disease is the leading cause of mortality in women
      costing more than 500,000 lives each year in the United States alone. Major
      depression in healthy subjects increases cardiovascular mortality in both men and
      women. The presence of major depression in patients with recent acute myocardial
      infarction (AMI) or unstable angina more than doubles the risk of cardiac death
      in both men and women. In the presence of depression, lack of social integration
      has an additive effect on cardiac events. Depression is more prevalent in women
      with coronary heart disease (CHD) than in men. Psychologic counseling as well as
      cognitive behavioral treatment in women post-AMI seems to adversely affect
      prognosis, whereas it has neutral effects in men. Pharmacologic treatment of
      depression with serotonin reuptake inhibitors is safe in men and women post-AMI
      and is particularly effective in patients with recurrent depression. Whether
      effective treatment of depression lowers cardiac mortality remains to be proven.

PMID- 15953794
TI  - Reflections on depression as a cardiac risk factor.
AB  - OBJECTIVE: Major North American cardiology organizations do not currently list
      depression among the officially recognized cardiac risk factors, yet many
      behavioral medicine specialists believe depression to be an important risk. We
      wondered what was missing from the available data. METHODS: The Medline, Current
      Contents, and PsychInfo databases were used to perform a systematic review of the
      literature linking depression and depressive symptoms with cardiac disease
      outcomes. Because of previous reviews, we paid particular attention to
      publications from 2001 to 2003. RESULTS: We identified 21 etiologic and 43
      prognostic publications that had prospective designs, used recognized measures of
      depression, and included objective outcome measures. We also identified 79 review
      articles. In addition to issues of sample size, sample characteristics, and
      timing of measures, we noted heterogeneity in the definitions of depression,
      frequent repeat publications from the same data sets, heterogeneity of outcome
      measures, a variety of approaches for covariate selection, and a preponderance of
      review articles, all factors that cannot help to convince skeptics. CONCLUSIONS:
      Despite these issues, the bulk of the data from prospective studies with
      recognized indices of depression and objective outcome measures is supportive of
      depression as a cardiac risk factor.

PMID- 15953796
TI  - Hypercortisolemia and depression.
AB  - Hypercortisolemia and dysregulation of the hypothalamic-pituitary-adrenal (HPA)
      axis are often found in severe forms of depression. The authors review the
      history of techniques used to assess the functions of the HPA axis, evidence for
      hypercortisolemia as a state rather than trait component of depression, and
      treatment implications.

PMID- 15953797
TI  - Depression, the autonomic nervous system, and coronary heart disease.
AB  - Depression is a risk factor for medical morbidity and mortality in patients with
      coronary heart disease (CHD). Dysregulation of the autonomic nervous system (ANS)
      may explain why depressed patients are at increased risk. Studies of medically
      well, depressed psychiatric patients have found elevated levels of plasma
      catecholamines and other markers of altered ANS function compared with controls.
      Studies of depressed patients with CHD have also uncovered evidence of ANS
      dysfunction, including elevated heart rate, low heart rate variability,
      exaggerated heart rate responses to physical stressors, high variability in
      ventricular repolarization, and low baroreceptor sensitivity. All of these
      indicators of ANS dysfunction have been associated with increased risks of
      mortality and cardiac morbidity in patients with CHD. Further research is needed
      to determine whether ANS dysfunction mediates the effects of depression on the
      course and outcome of CHD, and to develop clinical interventions that improve
      cardiovascular autonomic regulation while relieving depression in patients with
      CHD.

PMID- 15953798
TI  - Depression, alterations in platelet function, and ischemic heart disease.
AB  - Platelets, the smallest corpuscular component of human blood, are central to
      various crucial biologic pathways in the human body. Diminished platelet function
      is thought to contribute to the increased risk of ischemic heart disease in
      patients with major depressive disorder, and to the increased morbidity and
      diminished survival of depressed patients after an index myocardial infarction.
      We reviewed both recent studies that evaluated platelet function in various
      patient groups and recent information regarding the potential beneficial effects
      of selective serotonin reuptake inhibitors on platelet reactivity.

PMID- 15953799
TI  - The role of immune system parameters in the relationship between depression and
      coronary artery disease.
AB  - The relationship between depressive symptoms and coronary artery disease (CAD) is
      mediated in part by immune system parameters. This review describes research on
      the psychoneuroimmunological pathways accounting for the association between
      depression and CAD, and addresses conceptual and methodological issues.
      Relationships between central nervous system correlates of depression and immune
      system parameters are bidirectional and are mediated via neurohormonal and
      parasympathetic pathways. Evidence suggests that these associations can be
      affected by a) the clinical characteristics of depression (e.g., typical
      depression versus atypical depression and exhaustion), b) the duration and
      severity of depressive symptoms, and c) the stage of underlying CAD. Depressive
      symptoms are hypothesized to affect primarily the transition from stable CAD to
      acute coronary syndromes via plaque activation and prothrombotic processes, and
      may play an additional role in the response to injury at early stages of coronary
      atherosclerosis.

PMID- 15953800
TI  - Depression and smoking in coronary heart disease.
AB  - OBJECTIVE: This review examines the relationship between depression and smoking
      in coronary heart disease (CHD). It summarizes relevant findings from general
      population and smoking cessation studies and discusses the few studies that have
      investigated whether smoking confounds, mediates, or moderates the effect of
      depression on cardiac morbidity and mortality. METHODS: Qualitative review of
      research literature. RESULTS: Although many studies of the prognostic importance
      of depression in CHD have adjusted for smoking, there is no convincing evidence
      that smoking actually confounds the relationship between depression and CHD.
      There is also no evidence that smoking moderates this relationship. There is,
      however, limited evidence that smoking may partially mediate the effect of
      depression on morbidity and mortality in CHD. CONCLUSION: We need more research
      on the relationship between depression and smoking in CHD to develop a more
      complete model of the mechanisms linking depression to cardiac morbidity and
      mortality.

PMID- 15953801
TI  - Psychologic functioning and physical health: a paradigm of flexibility.
AB  - Recent evidence suggests that positive psychologic factors may be protective
      against coronary artery disease (CAD). We consider this possibility through a
      paradigm that explores three interrelated factors that may promote healthy
      psychologic functioning: vitality, emotional flexibility, and coping flexibility.
      Vitality is a positive and restorative emotional state that is associated with a
      sense of enthusiasm and energy. Flexibility is related both to the ability to
      regulate emotions effectively and cope effectively with challenging daily
      experiences. A variety of factors may diminish vitality, including chronic stress
      and negative emotions. Pathophysiologically, chronic stress and negative
      emotional states can both invoke a "chronic stress response" characterized by
      increased stimulation of the sympathetic nervous system and hypothalamic
      pituitary-adrenal axis, with resultant peripheral effects, including augmented
      heart rate and blood pressure responsiveness and delayed recovery to stressful
      stimuli. Research indicates a wide array of stressful conditions--associated with
      either elements of relative inflexibility in psychologic functioning and/or
      relatively unabated stressful stimulation--that are associated with this type of
      exhausting hyperarousal. Conversely, new data suggest that positive psychologic
      factors, including positive emotions, optimism, and social support, may diminish
      physiological hyperresponsiveness and/or reduce adverse clinical event rates.
      Still other positive factors such as gratitude and altruistic behavior have been
      linked to a heightened sense of well-being but have not yet been tested for
      beneficial physiological effects. Pending further study, these observations could
      serve as the basis for expanding the potential behavioral interventions that may
      be used to assist patients with psychosocial risk factors for CAD.

PMID- 15953802
TI  - Pharmacologic treatment of depression in patients with heart disease.
AB  - The relationship between depression and cardiovascular disease is complex and
      multifaceted. There is a growing body of evidence that depression significantly
      and adversely affects cardiovascular health. Perhaps the most prominent finding
      is the documented increase in mortality rate in patients with depression after
      myocardial infarction. The critical questions of interest to both the clinician
      and researcher are whether there are safe and effective treatments for depression
      in patients with heart disease and whether treatment of depression reduces the
      increased risk of cardiac morbidity and mortality. Although the data are limited
      and are primarily from open or comparator trials, the tricyclics (TCAs) and
      selective serotonin reuptake inhibitors (SSRI) are effective for treatment of
      depression in patients with ischemic heart disease (IHD), and response rates are
      comparable with those reported in depressed patients without heart disease. In
      terms of safety, the TCAs are associated with documented adverse cardiovascular
      effects, including increases in heart rate, orthostatic hypotension, and
      conduction delays. Use of TCAs in patients with IHD carries a proven increased
      risk of cardiac morbidity and perhaps of mortality as well. The SSRI appear to be
      relatively safe and effective in the treatment for depression in patients with
      comorbid IHD.

PMID- 15953803
TI  - Nonpharmacologic treatments for depression in patients with coronary heart
      disease.
AB  - OBJECTIVES: We review nonpharmacologic treatments for depression in patients with
      coronary heart disease (CHD), including psychological therapies such as cognitive
      behavior therapy (CBT) and interpersonal therapy (IPT), aerobic exercise, St.
      John's wort (SJW), essential fatty acids (EFAs), S-Adenosylmethionine (SAMe),
      acupuncture, and chromium picolinate (CP). METHOD: Medline searches and reviews
      of bibliographies were used to identify relevant articles. Each treatment was
      reviewed with particular attention paid to empirical support, as well as to
      potential mechanisms of action that might affect not only depression but also CHD
      endpoints. RESULTS: Nearly all randomized controlled trials (RCTs) of depression
      treatments have been conducted with non-CHD patients. These studies have provided
      the most support for psychological treatments, particularly CBT and IPT. Aerobic
      exercise, SJW, and SAMe also have considerable empirical support in otherwise
      healthy persons, but SJW may have undesirable side effects for CHD patients. Data
      for EFAs, CP, and acupuncture are limited; however, the use of aerobic exercise
      shows considerable promise for cardiac patients. CONCLUSIONS: There are few RCTs
      of patients with clinical depression and CHD, and those that exist have
      significant methodological limitations. Nonetheless, there is preliminary
      evidence that nonpharmacologic treatments are effective for cardiac patients with
      depression. In terms of reducing depression, the most evidence exists for
      psychological treatments, particularly CBT and IPT. However, there is little
      evidence that such treatment would also improve CHD risk factors. Aerobic
      exercise offers more promise to improve both mental and physical health due to
      its effect on cardiovascular risk factors and outcomes and thus warrants
      particular attention in future trials.

PMID- 15953804
TI  - Definitions and distinctions among depressive syndromes and symptoms:
      implications for a better understanding of the depression-cardiovascular disease
      association.
AB  - OBJECTIVES: A prognostic role for depressive disorder presence and/or elevated
      depressive symptoms in the onset and recurrence of cardiovascular disease has
      been largely supported. Depression is a multifaceted disorder, encompassing a
      wide range of somatic, cognitive, and mood symptoms; it varies in intensity,
      duration, frequency, course, and family history; it can be assessed continuously
      or categorically; it can be obtained by interview or by self-report; and
      importantly, the cardiac prognostic impact of these distinctions may vary. We
      provide an overview of definitions and possible assessment of depression, and we
      discuss key assessment distinctions. CONCLUSION: Examining the predictive ability
      of these key distinctions of depression for acute coronary syndrome recurrence
      would be of benefit to future research in this field.

PMID- 15953805
TI  - Lessons from SADHART, ENRICHD, and other trials.
AB  - Depression is highly prevalent in patients with cardiovascular disease and is
      independently associated with a poor prognosis when present. A very important
      aspect of continued therapeutic advances in this field will be the ability to
      show a convincing connection between the treatment of depression in patients with
      heart disease and a reduction in morbidity and mortality associated with the co
      occurrence of these conditions. The recent SADHART (Sertraline AntiDepressant
      Heart Attack Trial) investigation demonstrated that sertraline is safe and
      efficacious in depressed patients with ischemic heart disease but was
      underpowered to detect a mortality difference between sertraline and placebo. The
      ENRICHD (ENhancing Recovery in Coronary Heart Disease) trial showed that
      cognitive-behavioral therapy is effective for treating depression but had no
      impact on cardiovascular morbidity or mortality. There are a number of
      methodologic complexities associated with research regarding depression and
      cardiovascular disease, including difficulties in the definition and measurement
      of depression, complexities in the conduction of large-scale trials, ethical
      considerations surrounding the use of placebo, and interpretation of trial
      results. In addition, the lack of certainty regarding the pathophysiologic link
      between depression and cardiovascular disease means that there is a lack of
      pharmacotherapy targeted specifically at the dysregulated physiology that might
      explain the increased morbidity and mortality seen when these two conditions
      occur together.

PMID- 15953806
TI  - Integrating psychologic approaches into the behavioral management of cardiac
      patients.
AB  - Despite increasing evidence that depression and other psychologic risk factors
      promote atherosclerosis and adverse cardiac events, practice guidelines for
      integrating psychologic considerations into the management of cardiac patients
      are currently lacking. This review explores how application of psychologic
      principles may help physicians to implement three basic approaches for improving
      the behavioral management of cardiac patients. The first is the identification
      and reduction of barriers to following behavioral recommendations, including the
      presence of negative mood states and other psychologic factors. Patients often
      self-manage negative moods through unhealthy behaviors such as smoking or eating.
      However, replacement of these behaviors with more health-promoting behaviors such
      as exercise and stress management techniques is often difficult and may require
      active assistance. Second, physicians should help provide patients with external
      support systems such as referral to support groups or telephone follow ups, when
      necessary. Such external supports, however, often require other approaches for
      long-term maintenance of new health behaviors. Third, a motivational literature
      suggests that physicians can promote patient self-management by formulating
      health goals in a manner that satisfies "basic psychologic needs" such as the
      needs for autonomy and competency. Satisfaction of these needs increases
      "vitality" (a positive state of energy and enthusiasm). Motivation can also be
      enhanced by creating an emotional attachment to health goals. A case example is
      provided to illustrate the application of these concepts in clinical practice,
      and future directions are discussed, including a potential healthcare model that
      could make the behavioral management of patients more feasible in cardiac
      practice.

PMID- 15953807
TI  - Oxidative Mechanisms in Neurodegenerative Disorders. Proceedings from a satellite
      symposium, Guilin, China, 7-11 February 2004.
AB  - This special issue of Molecular Neurobiology presents a series of mini-reviews
      resulting from an ISN satellite symposium entitled Oxidative Mechanisms in
      Neurodegenerative Disorders Held at the Guilin Park Hotel, Guilin, China on
      February 7-11, 2004. The timely topics in this symposium were contributed by more
      than 20 internationally acclaimed scientists and attended by more than 100
      participants interested in this subject matter. This satellite symposium was also
      part of the 6th Biennial Asian-Pacific Society for Neurochemistry (APSN) meeting
      held in Hong Kong, China. Organizers included Dr. Piu Chan (Capital University of
      Medical Sciences and Beijing Institute of Geriatrics) Dr. Albert Y. Sun and Dr.
      Grace Y. Sun (University of Missouri, Columbia, MO). The satellite meeting was
      hosted by Xuanwu Hospital of Capital University of Medical Sciences and Guilin
      Medical College, and was generously supported by the following: the International
      Society of Neurochemistry (ISN), National Institutes of Health (USA) (1 R13
      NS047414), the Geriatric Research, Education and Clinical Center (GRECC) VA
      Medical Center, Minneapolis, MN, USA, The Chinese Society of Neuroscience,
      Chinese Medical Association, Chinese Journal of Neurology, Shanghai Roche
      Pharmaceuticals Ltd., and Beijing QuiXave United Technology Ltd. Corporation.

PMID- 15953808
TI  - Kainic acid-mediated excitotoxicity as a model for neurodegeneration.
AB  - Neuronal excitation involving the excitatory glutamate receptors is recognized as
      an important underlying mechanism in neurodegenerative disorders. Excitation
      resulting from stimulation of the ionotropic glutamate receptors is known to
      cause the increase in intracellular calcium and trigger calcium-dependent
      pathways that lead to neuronal apoptosis. Kainic acid (KA) is an agonist for a
      subtype of ionotropic glutamate receptor, and administration of KA has been shown
      to increase production of reactive oxygen species, mitochondrial dysfunction, and
      apoptosis in neurons in many regions of the brain, particularly in the
      hippocampal subregions of CA1 and CA3, and in the hilus of dentate gyrus (DG).
      Systemic injection of KA to rats also results in activation of glial cells and
      inflammatory responses typically found in neurodegenerative diseases. KA-induced
      selective vulnerability in the hippocampal neurons is related to the distribution
      and selective susceptibility of the AMPA/kainate receptors in the brain. Recent
      studies have demonstrated ability of KA to alter a number of intracellular
      activities, including accumulation of lipofuscin-like substances, induction of
      complement proteins, processing of amyloid precursor protein, and alteration of
      tau protein expression. These studies suggest that KA-induced excitotoxicity can
      be used as a model for elucidating mechanisms underlying oxidative stress and
      inflammation in neurodegenerative diseases. The focus of this review is to
      summarize studies demonstrating KA-induced excitotoxicity in the central nervous
      system and possible intervention by anti-oxidants.

PMID- 15953809
TI  - Role of mitochondrial dysfunction and oxidative stress in the pathogenesis of
      selective neuronal loss in Wernicke's encephalopathy.
AB  - Thiamine deficiency results in Wernicke's encephalopathy and is commonly
      encountered in chronic alcoholism, gastrointestinal diseases, and HIV AIDS. The
      earliest metabolic consequence of thiamine deficiency is a selective loss in
      activity of the thiamine diphosphate-dependent enzyme alpha-ketoglutarate
      dehydrogenase (alpha-KGDH), a rate-limiting tricarboxylic acid cycle enzyme.
      Thiamine deficiency is characterized neuropathologically by selective neuronal
      cell death in the thalamus, pons, and cerebellum. The cause of this region
      selective neuronal loss is unknown, but mechanisms involving cellular energy
      failure, focal lactic acidosis, and NMDA receptor-mediated excitotoxicity have
      classically been implicated. More recently, evidence supports a role for
      oxidative stress. Evidence includes increased endothelial nitric oxide synthase,
      nitrotyrosine deposition, microglial activation, and lipid peroxidation. Reactive
      oxygen species production results in decreased expression of astrocytic glutamate
      transporters and decreased activities of alpha-KGDH, resulting in an
      amplification of cell death mechanisms in thiamine deficiency.

PMID- 15953810
TI  - Phospholipase A2 in astrocytes: responses to oxidative stress, inflammation, and
      G protein-coupled receptor agonists.
AB  - Astrocytes comprise the major cell type in the central nervous system (CNS) and
      they are essential for support of neuronal functions by providing nutrients and
      regulating cell-to-cell communication. Astrocytes also are immune-like cells that
      become reactive in response to neuronal injury. Phospholipases A2 (PLA2) are a
      family of ubiquitous enzymes that degrade membrane phospholipids and produce
      lipid mediators for regulating cellular functions. Three major classes of PLA2
      are expressed in astrocytes: group IV calcium-dependent cytosolic PLA2 (cPLA2),
      group VI calcium-independent PLA2 (iPLA2), and group II secretory PLA2(sPLA2).
      Upregulation of PLA2 in reactive astrocytes has been shown to occur in a number
      of neurodegenerative diseases, including stroke and Alzheimer's disease. This
      review focuses on describing the effects of oxidative stress, inflammation, and
      activation of G protein-coupled receptors on PLA2 activation, arachidonic acid
      (AA) release, and production of prostanoids in astrocytes.

PMID- 15953811
TI  - The alpha-ketoglutarate-dehydrogenase complex: a mediator between mitochondria
      and oxidative stress in neurodegeneration.
AB  - Damage from oxidative stress and mitochondrial dysfunction occur together in many
      common neurodegenerative diseases. The enzymes that form the mitochondrial alpha
      ketoglutarate- dehydrogenase complex (KGDHC), a key and arguably rate-limiting
      enzyme system of the tricarboxylic acid cycle, might mediate the interaction of
      these processes. KGDHC activity is reduced in numerous age-related
      neurodegenerative diseases and is diminished by oxidative stress. In Alzheimer's
      disease (AD), the reduction correlates highly to diminished mental performance.
      Thus, research has focused on the mechanisms by which select oxidants reduce
      KGDHC and the consequences of such a reduction. Diminished KGDHC in cells is
      associated with apoptosis without changes in the mitochondrial membrane
      potential. Studies of isolated mitochondria and of animal models suggest that a
      reduction in KGDHC can predispose to damage by other toxins that promote
      neurodegeneration. Diminished oxidative metabolism can be plausibly linked to
      pathological features of neurodegenerative diseases (e.g., reduced mental
      function, the plaques and tangles in AD). Thus, reductions in KGDHC might be
      central to the pathophysiology of these diseases. Studies of proteins, cells,
      animal models, and humans suggest that treatments to diminish, or bypass, the
      reduction in KGDHC might be beneficial in age-related neurodegenerative
      disorders.

PMID- 15953812
TI  - Mechanisms for inhibition of P2 receptors signaling in neural cells.
AB  - Trophic factors are required to ensure neuronal viability and regeneration after
      neural injury. Although abundant information is available on the factors that
      cause the activation of astrocytes, little is known about the molecular
      mechanisms underlying the regulation of this process. Nucleotides released into
      the extracellular space from injured or dying neural cells can activate
      astrocytes via P2 nucleotide receptors. After a brief historical review and
      update of novel P2 receptor antagonists, this article focuses on recent
      advancements toward understanding molecular mechanisms that regulate G protein
      coupled P2Y receptor signaling. Among P2Y receptor subtypes, the heptahelical
      P2Y2 nucleotide receptor interacts with vitronectin receptors via an RGD sequence
      in the first extracellular loop, and this interaction is required for effective
      signal transduction to activate mitogen-activated protein kinases ERK1/2, to
      mobilize intracellular calcium stores via activation of phospholipase C, protein
      kinase C isoforms, and to activate focal adhesion kinase and other signaling
      events. Ligation of vitronectin receptors with specific antibodies caused an
      inhibition of P2Y2 receptor-induced ERK1/2 and p38 phosphorylation and P2Y2
      receptor-induced cytoskeleton rearrangement and DNA synthesis. Structure-function
      studies have identified agonist-induced phosphorylation of the C-terminus of the
      P2Y2 receptor, an important mechanism for receptor desensitization. Understanding
      selective mechanisms for regulating P2Y2 receptor signaling could provide novel
      targets for therapeutic strategies in the management of brain injury,
      synaptogenesis, and neurological disorders.

PMID- 15953813
TI  - Oxidative stress in mitochondria: decision to survival and death of neurons in
      neurodegenerative disorders.
AB  - In mitochondria, oxidative phosphorylation and enzymatic oxidation of biogenic
      amines by monoamine oxidase produce reactive oxygen and nitrogen species, which
      are proposed to cause neuronal cell death in neurodegenerative disorders,
      including Parkinson's and Alzheimer's disease. In these disorders, mitochondrial
      dysfunction, increased oxidative stress, and accumulation of oxidation-modified
      proteins are involved in cell death in definite neurons. The interactions among
      these factors were studied by use of a peroxynitrite-generating agent, N
      morpholino sydnonimine (SIN-1) and an inhibitor of complex I, rotenone, in human
      dopaminergic SH-SY5Y cells. In control cells, peroxynitrite nitrated proteins,
      especially the subunits of mitochondrial complex I, as 3-nitrotyrosine,
      suggesting that neurons are exposed to constant oxidative stress even under
      physiological conditions. SIN-1 and an inhibitor of proteasome, carbobenzoxy-L
      isoleucyl-gamma-t-butyl-L-alanyl-L-leucinal (PSI), increased markedly the levels
      of nitrated proteins with concomitant induction of apoptosis in the cells.
      Rotenone induced mitochondrial dysfunction and accumulation and aggregation of
      proteins modified with acrolein, an aldehyde product of lipid peroxidation in the
      cells. At the same time, the activity of the 20S beta-subunit of proteasome was
      reduced significantly, which degrades oxidative-modified protein. The mechanism
      was proved to be the result of the modification of the 20S beta-subunit with
      acrolein and to the binding of other acrolein-modified proteins to the 20S beta
      subunit.

PMID- 15953814
TI  - Signaling from P2 nucleotide receptors to protein kinase cascades induced by CNS
      injury: implications for reactive gliosis and neurodegeneration.
AB  - Gliosis is a hypertrophic and hyperplastic response to many types of central
      nervous system injury, including trauma, stroke, seizure, as well as
      neurodegenerative and demyelinating disorders. Reactive astrocytes, a major
      component of the glial scar, express molecules that can both inhibit and promote
      axonal regeneration. ATP, which is released upon traumatic injury, hypoxia, and
      cell death, contributes to the gliotic response by binding to specific cell
      surface astrocytic P2 nucleotide receptors and evoking characteristic features of
      gliosis such as increased expression of glial fibrillary acidic protein (GFAP),
      generation and elongation of astrocytic processes, and cellular proliferation.
      Here, we review recent studies that demonstrate that (1) metabotropic, P2Y, and
      ionotropic, P2X, receptors expressed in astrocytes are coupled to protein kinase
      signaling pathways that regulate cellular proliferation, differentiation, and
      survival such as ERK and protein kinase B/Akt and (2) these P2 receptor/protein
      kinase cascades are activated after trauma induced by mechanical strain. We
      suggest that P2 receptor/protein kinase signaling pathways might provide novel
      therapeutic targets to regulate the formation of reactive astrocytes and the
      production of molecules that affect axonal regeneration and neurodegeneration.

PMID- 15953815
TI  - Oxidative stress and neuronal death/survival signaling in cerebral ischemia.
AB  - It has been demonstrated by numerous studies that apoptotic cell death pathways
      are implicated in ischemic cerebral injury in ischemia models in vivo.
      Experimental ischemia and reperfusion models, such as transient focal/global
      ischemia in rodents, have been thoroughly studied and the numerous reports
      suggest the involvement of cell survival/death signaling pathways in the
      pathogenesis of apoptotic cell death in ischemic lesions. In these models,
      reoxygenation during reperfusion provides oxygen as a substrate for numerous
      enzymatic oxidation reactions and for mitochondrial oxidative phosphorylation to
      produce adenosine triphosphate. Oxygen radicals, the products of these
      biochemical and physiological reactions, are known to damage cellular lipids,
      proteins, and nucleic acids and to initiate cell signaling pathways after
      cerebral ischemia. Genetic manipulation of intrinsic antioxidants and factors in
      the signaling pathways has provided substantial understanding of the mechanisms
      involved in cell death/survival signaling pathways and the role of oxygen
      radicals in ischemic cerebral injury. Future studies of these pathways could
      provide novel therapeutic strategies in clinical stroke.

PMID- 15953817
TI  - Polyphenols in cerebral ischemia: novel targets for neuroprotection.
AB  - Plant polyphenols are dietary components that exert a variety of biochemical and
      pharmacological effects. Recently, considerable interest has been focused on
      polyphenols because of their antioxidant, anti-inflammatory, and
      antiproliferative activities. Oxidative stress is thought to be a key event in
      the pathogenesis of cerebral ischemia. Overproduction of reactive oxygen species
      during ischemia/reperfusion could cause an imbalance between oxidative and
      antioxidative processes. Reactive oxygen species can damage lipids, proteins, and
      nucleic acids, thereby inducing apoptosis or necrosis. There is increasing
      evidence supporting the hypothesis that plant polyphenols can provide protection
      against neurodegenerative changes associated with cerebral ischemia. This article
      reviews the neuroprotective effects of plant extracts and their constituents that
      have been used in animal models of cerebral ischemia. The use of polyphenols as
      therapeutic agents in stroke has been suggested.

PMID- 15953816
TI  - Similarities and differences between the Wnt and reelin pathways in the forming
      brain.
AB  - One of the key features in development is the reutilization of successful
      signaling pathways. Here, we emphasize the involvement of the Wnt pathway, one of
      the five kinds of signal transduction pathway predominating early embryonic
      development of all animals, in regulating the formation of brain structure. We
      discuss the interrelationships between the Wnt and reelin pathways in the
      regulation of cortical layering. We summarize data emphasizing key molecules,
      which, when mutated, result in abnormal brain development. This integrated view,
      which is based on conservation of pathways, reveals the relative position of
      participants in the pathway, points to control mechanisms, and allows raising
      testable working hypotheses. Nevertheless, although signaling pathways are highly
      conserved from flies to humans, the overall morphology is not. We propose that
      future studies directed at understanding of diversification will provide fruitful
      insights on mammalian brain formation.

PMID- 15953818
TI  - Poly(ADP-ribose) polymerase: the nuclear target in signal transduction and its
      role in brain ischemia-reperfusion injury.
AB  - Poly(ADP-ribose) polymerase (PARP)-1 is a DNA nick sensor that transforms ADP
      ribose from betaNAD+ in the form of polymer to over 40 nuclear proteins,
      particularly to histones, several transcription factors, and PARP itself,
      modulating their activities and functions. PARP-1 activated by DNA breaks
      facilitates transcription, replication, and DNA base excision repair. The last
      studies indicate that PARP-1 is the new nuclear target for fast signals evoked in
      cell membranes by depolarization and cholinergic and glutaminergic receptors
      stimulation. Excessive activation of PARP-1 by peroxynitrate-evoked DNA damage
      during oxidative stress can cause cell death by NAD+/ATP depletion after ischemia
      reperfusion injury, inflammation, and diabetes mellitus. The PARP-1 through
      interaction with nuclear factor-kappaB, p53, and other transcription factors
      might significantly modulate cell survival and death and a type of death pathway.
      The pharmacological modulation of PARP-1 might offer a new effective approach for
      neuroprotection.

PMID- 15953819
TI  - Molecular determinants of P2Y2 nucleotide receptor function: implications for
      proliferative and inflammatory pathways in astrocytes.
AB  - In the mammalian nervous system, P2 nucleotide receptors mediate
      neurotransmission, release of proinflammatory cytokines, and reactive
      astrogliosis. Extracellular nucleotides activate multiple P2 receptors in neurons
      and glial cells, including G protein-coupled P2Y receptors and P2X receptors,
      which are ligand-gated ion channels. In glial cells, the P2Y2 receptor subtype,
      distinguished by its ability to be equipotently activated by ATP and UTP, is
      coupled to pro-inflammatory signaling pathways. In situ hybridization studies
      with rodent brain slices indicate that P2Y2 receptors are expressed primarily in
      the hippocampus and cerebellum. Astrocytes express several P2 receptor subtypes,
      including P2Y2 receptors whose activation stimulates cell proliferation and
      migration. P2Y2 receptors, via an RGD (Arg-Gly-Asp) motif in their first
      extracellular loop, bind to alphavbeta3/beta5 integrins, whereupon P2Y2 receptor
      activation stimulates integrin signaling pathways that regulate cytoskeletal
      reorganization and cell motility. The C-terminus of the P2Y2 receptor contains
      two Src-homology-3 (SH3)-binding domains that upon receptor activation, promote
      association with Src and transactivation of growth factor receptors. Together,
      our results indicate that P2Y2 receptors complex with both integrins and growth
      factor receptors to activate multiple signaling pathways. Thus, P2Y2 receptors
      present novel targets to control reactive astrogliosis in neurodegenerative
      diseases.

PMID- 15953820
TI  - Is hypercholesterolemia a risk factor for Alzheimer's disease?
AB  - There is considerable attention being given to the association of Alzheimer's
      disease and cholesterol homeostasis. To that end, some have suggested that
      elevated cholesterol levels are a risk factor for Alzheimer's disease. If
      elevated cholesterol is a risk factor for Alzheimer's disease, then it would be
      expected that patients with Alzheimer's disease would have elevated serum and
      brain cholesterol levels. Studies were reviewed that have examined cholesterol
      levels in Alzheimer's patients and control subjects, including prospective
      studies, and based on that review, the conclusion is reached that the majority of
      studies do not support elevated cholesterol levels in serum and brain as a risk
      factor for Alzheimer's disease. Alternative hypotheses are discussed, including
      cholesterol domains and subgroups of individuals with hypercholesteremia.

PMID- 15953821
TI  - Metabolic investigation in psychiatric disorders.
AB  - A multiplicity of theories have been proposed over the years that aim to
      conceptualize the pathophysiology of neuropsychiatric disorders, including
      impaired neurotransmission, viral infections, genetic mutation, energy metabolism
      deficiency, excitotoxicity, oxidative stress, and others. It is likely that
      complex disorders such as schizophrenia, bipolar disorder, and major depression
      are associated with multiple etiologies and pathogenetic mechanisms. In light of
      the interwoven biochemistry of human organs, identifying a network of multiple
      interacting biochemical pathways that account for the constellation of clinical
      and biological features would advance our understanding of these disorders. One
      such approach is to evaluate simultaneously the multiple metabolites in order to
      uncover the dynamic relations in the relevant biochemical systems. These
      metabolites are a group of low-molecular-weight, redox-active compounds, such as
      antioxidants, amino acids, catecholamines vitamins, lipids, and nucleotides,
      which reflect the metabolic processes, including anabolism and catabolism as well
      as other related cellular processes (e.g., signal transduction, regulation,
      detoxification, etc.). Such an analytic approach has the potential to yield
      valuable insights into the likely complex pathophysiological mechanisms that
      affect multiple metabolic pathways and thereby offer multiple windows of
      therapeutic opportunities.

PMID- 15953823
TI  - Synaptic signaling by lipids in the life and death of neurons.
AB  - Synaptic activity promotes the regulated formation of lipid messengers through
      phospholipase-mediated cleavage of specific phospholipid reservoirs from
      membranes. Multiple effectors trigger the formation of lipid messengers,
      including neurotransmitters, membrane depolarization, ion channels, cytokines,
      and neurotrophic factors. Lipid messengers in turn modulate and interact with
      other signaling cascades, contributing to the development, differentiation,
      function (e.g., long-term potentiation [LTP] and memory), protection, and repair
      of cells in the nervous system. These relationships with other signaling cascades
      remain largely to be investigated. Oxidative stress disrupts lipid signaling,
      enhances lipid peroxidation, and initiates and propagates neurodegeneration.
      There is growing evidence that lipid messengers participate in the extensive
      interactions among neurons, astrocytes, oligodendrocytes, microglia, cells of the
      microvasculature, and other cells. This article provides an example of how
      signaling by lipids regulates critical events essential for neuronal survival and
      reviews the recent identification of a novel endogenous neuroprotective signaling
      pathway involving a docosahexaenoic acid-derived mediator.

PMID- 15953822
TI  - Oxidative imbalance in Alzheimer's disease.
AB  - Oxidative stress is a striking feature of susceptible neurons in the Alzheimer's
      disease brain. Importantly, because oxidative stress is an early event in
      Alzheimer's disease, proximal to the development of hallmark pathologies, it
      likely plays an important role in the pathogenesis of the disease. Investigations
      into the cause of such oxidative stress show that interactions between abnormal
      mitochondria and disturbed metal metabolism are, at least in part, responsible
      for cytoplasmic oxidative damage observed in these susceptible neurons, which
      could ultimately lead to their demise. Oxidative stress not only temporally
      precedes the pathological lesions of the disease but could also contribute to
      their formation, which, in turn, could provide some protective mechanism to
      reduce oxidative stress and ensure that neurons do not rapidly succumb to
      oxidative insults. In this review, we present the evidence for oxidative stress
      in Alzheimer's disease and its likely sources and consequence in relation to
      other pathological changes.

PMID- 15953824
TI  - Effects of hypoxia on the proliferation and differentiation of NSCs.
AB  - Oxygen is vital to nearly all forms of life on Earth via its role in energy
      homeostasis and other cell functions. Until recently, the effects of oxygen on
      the proliferation and differentiation of neural stem cells (NSCs) have been
      largely ignored. Some studies have been carried out on the basis of the fact that
      NSCs exists within a "physiological hypoxic" environment at 1 to 5% O2 in both
      embryonic and adult brains. The results showed that hypoxia could promote the
      growth of NSCs and maintain its survival in vitro. In vivo studies also showed
      that ischemia/hypoxia increased the number of endogenous NSCs in the
      subventricular zone and dentate gyrus. In addition, hypoxia could influence the
      differentiation of NSCs. More neurons, especially more doparminergic neurons,
      were produced under hypoxic condition. The effects of hypoxia on the other kind
      of stem cell were briefly introduced as additional evidence. The mechanism of
      these responses might be primarily involved in the hypoxic inducible factor-1
      (HIF-1) signal pathway. The present review summarizes recent works on the role of
      hypoxia in the proliferation and differentiation of NSCs both in vitro and in
      vivo, and the mechanism involved in HIF-1 signaling pathway behind this response
      was also discussed.

PMID- 15953826
TI  - Hypoxic preconditioning: a novel intrinsic cytoprotective strategy.
AB  - A concept of tissue-cell adaptation to hypoxia (hypoxic preconditioning) is
      raised and its corresponding animal model is introduced. A significantly
      strengthened tolerance to hypoxia and a protective effect of the brain extracts
      from the preconditioned animals are presented. Changes in animals' behavior,
      neuromorphology, neurophysiology, neurochemistry and molecular neurobiology
      during preconditioning are described. Energy saving, hypometabolism, and cerebral
      protection in particular are thought to be involved in the development of hypoxic
      tolerance and tissue-cell protection. The essence and significance of the hypoxic
      tissue-cell adaptation or preconditioning are discussed in terms of biological
      evolution and practical implication.

PMID- 15953825
TI  - Alpha-synuclein and dopamine metabolism.
AB  - alpha-Synuclein (alpha-Syn), a 140-amino-acid protein richly expressed in
      presynaptic terminals in the central nervous system, has been shown to play a
      central role in the pathogenesis of Parkinson's disease. Although the normal
      functions of alpha-Syn remain elusive, accumulating evidence shows that the
      molecule is involved in multiple steps related to dopamine metabolism, including
      dopamine synthesis, storage, release, and uptake. The regulatory effect of alpha
      Syn on dopamine metabolism is likely to tone down the amount of cytoplasmic
      dopamine at nerve terminals, thereby limiting its conversion to highly reactive
      oxidative molecules. Formation of alpha-Syn protofibrils triggered by factors
      such as gene mutations and environmental toxins can make the molecule lose its
      normal functions, leading to disrupted homeostasis of dopamine metabolism,
      increased cytoplasmic dopamine levels, and enhanced oxidative stress in
      dopaminergic neurons. The enhanced oxidative stress will, in turn, exacerbate the
      formation of alpha-Syn protofibrils and drive the neurons into a vicious cycle,
      which will finally result in the selective degeneration of the dopaminergic
      neurons associated with Parkinson's disease.

PMID- 15953827
TI  - Environmental toxins and alpha-synuclein in Parkinson's disease.
AB  - In recent years, environmental influences have been thought to play an important
      role in Parkinson's disease (PD). Evidence from epidemiological investigations
      suggests that environmental factors might take part in the disease process.
      Intriguingly, most of environmental toxins share the common mechanism of causing
      mitochondria dysfunction by inhibiting complex I and promoting alpha-synuclein
      aggregation, a key factor in PD. Therefore, understanding the mechanism of
      interactions between alpha-synuclein and environmental factors could lead to new
      therapeutic approaches to PD.

PMID- 15953830
TI  - Introduction: laboratory animals and immunization procedures: challenges and
      opportunities.

PMID- 15953829
TI  - Pharmacological study of the novel compound FLZ against experimental Parkinson's
      models and its active mechanism.
AB  - FLZ is a synthetic new derivative of squamosamide. Pharmacological study found
      that FLZ given orally improved the abnormal behavior caused by the functional
      disturbance of dopaminergic and cholinergic neurons in mice. FLZ significantly
      increased the content of dopamine and its metabolites in striatum in MPTP model
      mice. FLZ also remarkably protected dopaminergic PC-12 cells against dopamine and
      MPP+ induced injury and apoptosis in vitro. The compound inhibited the formation
      of dopamine-melanin and protein polymers. Additionally, FLZ inhibited cytochrome
      c release from mitochondria and caspase-3 activation by dopamine in PC-12 cells.
      The above results suggest that compound FLZ possesses anti-PD activity through
      neuroprotection.

PMID- 15953828
TI  - Natural antioxidants for neurodegenerative diseases.
AB  - The author reviews the studies on the preventing effects of natural antioxidants,
      such as vitamins E and C, flavonoids, and polyphenols on neurodegenerative
      diseases, especially summarizing the results on the protective effect of ginkgo
      biloba extract on neuron cells, preventing effects of green tea polyphenols on
      apoptosis of PC12 cells (Parkison's disease model), preventing effects of
      genestien on amyloid-beta-induced apoptosis of hippocampal neuronal cells
      (Alzhemer's disease model), and preventing effect of Crataegus flavonoids on
      ischemic-reperfusion damage to the brain of the Mongolian gerbil (stroke model)
      in the laboratory.

PMID- 15953831
TI  - Basic concepts of immune response and defense development.
AB  - The induction of immune responses requires critical interaction between innate
      parts of the immune system, which respond rapidly and in a relatively nonspecific
      manner, and other specific parts, which recognize particular epitopes on an
      antigen. A critical element in this interaction is the role played by dendritic
      cells (DCs), which represent "professional antigen-presenting cells." DCs
      endocytose and process antigen to peptide presented on the cell surface in
      association with major histocompatibility complex (MHC) molecules. This
      presentation results in interaction with and stimulation of helper T (Th)
      lymphocytes, which recognize peptide in association with either MHC class II or
      cytotoxic T (Tc) lymphocytes, which recognize peptide in association with MHC
      class I. Stimulation of Th lymphocytes produces the growth and differentiation
      factors (cytokines) essential for the B lymphocytes that have responded to a more
      intact form of the antigen and that differentiate into antibody-producing cells.
      The precise interaction between the cells depends on cognate ligand-receptor
      recognition between the B and Th lymphocytes. DCs also play a direct role with
      the stimulation of the B lymphocytes. It appears that DC can deliver antigen to
      the B lymphocytes in a more intact form than the processed form essential for
      stimulating T lymphocytes, and can release cytokines that assist the
      differentiation of the B lymphocytes into antibody-producing cells. This close
      relationship among the three cell types and the cytokines that are produced
      ensures the precise control and regulation necessary for immune response
      development.

PMID- 15953832
TI  - Applications and optimization of immunization procedures.
AB  - Classical immunization protocols have produced an antibody-based humoral response
      that is very effective against susceptible infectious diseases. Immunization
      introduces an external substance to induce the host immune system to respond
      specifically. Typically an antigen is used, but DNA, or a primed, pre-existing
      leukocyte or antigen-presenting cell, can also be used. Immunization is currently
      being used or investigated for the prevention and treatment of infectious
      diseases, cancer, addictions, allergies, pregnancy, and autoimmune diseases. It
      is also being used to produce biologically active materials such as polyclonal
      and monoclonal antibodies, antivenins, and anti-toxins for treating a wide range
      of conditions. Animals have been integral to the development of immunization
      techniques, as producers of toxoids and antitoxins, as models (e.g., to validate
      materials and protocols used for immunization, to understand the impact of
      immunization itself on the immune system, and to help investigators devise
      methods for determining the efficacy of vaccines) and as beneficiaries themselves
      of vaccines and antitoxins. The choice of immunization protocols is complex, and
      results may be affected by many factors such as dose and concentration of
      antigen, choice of adjuvants, time between inoculation and response measurement,
      and method of detection. The immune system responses to an antigen are also
      complex and continue to develop with advancing age. Anatomical, physiological,
      and immune system differences between species influence responses to
      immunization, as do the purity and presentation of the antigens and adjuvants.
      When directly comparing results, animals should be sourced from the same
      supplier. This review highlights the many uses of immunization techniques and
      introduces important considerations for the choice of protocols and animal
      models.

PMID- 15953833
TI  - Monoclonal versus polyclonal antibodies: distinguishing characteristics,
      applications, and information resources.
AB  - Antibodies are host proteins that comprise one of the principal effectors of the
      adaptive immune system. Their utility has been harnessed as they have been and
      continue to be used extensively as a diagnostic and research reagent. They are
      also becoming an important therapeutic tool in the clinician's armamentarium to
      treat disease. Antibodies are utilized for analysis, purification, and
      enrichment, and to mediate or modulate physiological responses. This overview of
      the structure and function of polyclonal and monoclonal antibodies describes
      features that distinguish one from the other. A limited review of their use as
      specific research, diagnostic, and therapeutic reagents and a list of printed and
      electronic resources that can be utilized to garner additional information on
      these topics are also included.

PMID- 15953834
TI  - Critical steps in the production of polyclonal and monoclonal antibodies:
      evaluation and recommendations.
AB  - Antibodies are valuable tools in the laboratory and clinic. Antibodies include
      those secreted by a single clone of B lymphocytes, termed monoclonal antibodies,
      and those produced by a mixture of various B lymphocyte clones, termed polyclonal
      antibodies. Both products have become essential instruments in fundamental
      immunological research, immunohistochemistry, diagnostic testing, and vaccine
      quality control. Antibody production requires a substantial number of animals,
      and the animals are subjected to a number of invasive procedures such as antigen
      injection and blood collection. However, by carefully designing an immunization
      protocol and by optimizing the immunization response, it is possible to minimize
      animals' pain and distress while obtaining optimal immune responses. In this
      article, the critical steps in the production of polyclonal and monoclonal
      antibodies are described, specifically including selection of the animal species
      and its age, injection protocol, and ascites tapping. Recommendations are
      provided for optimizing the immunization response.

PMID- 15953835
TI  - Adjuvants and antibody production: dispelling the myths associated with Freund's
      complete and other adjuvants.
AB  - Adjuvants have been used for more than 70 yr to enhance the immune response of
      the host animal to an antigen. Among the mechanisms that adjuvants use to enhance
      the immune response are the "depot" effect, antigen presentation, antigen
      targeting, immune activation/modulation, and cytotoxic lymphocyte induction. The
      immunostimulatory properties of adjuvants result in inflammation, tissue
      destruction, and the potential for resulting pain and distress in the host
      animal. The inflammatory lesions produced by adjuvants such as Freund's complete
      adjuvant (FCA) have led some to conclude that pain and distress are present, even
      in cases where the scientific evidence fails to support this conclusion.
      Recommendations and regulations in the literature, based on available scientific
      evidence, provide guidance on total adjuvant volumes, volumes per site, routes of
      injection, booster injections, and adjuvants used for antibody production. Among
      the numerous adjuvants that are used for experimental antibody production
      reviewed in this article, many claim to be less inflammatory, tissue destructive,
      and painful than FCA while producing equal or superior antibody responses.
      Although no adjuvant surpasses FCA for experimental antibody production against a
      wide range of antigenic molecules, many produce excellent antibody responses with
      less inflammation and tissue destruction. Balancing the requisite degree of
      immuno-stimulation and the extent of inflammation, necrosis, and potential pain
      and distress requires consideration of the nature of the antigen, the host immune
      responsiveness, the adjuvant's mechanisms of action, and the desired end-product.
      In cases where the antigen is a weak immunogen or has a very limited
      availability, the type and role of adjuvant becomes a critical component in
      producing an acceptable immune response and humoral antibody response.

PMID- 15953836
TI  - Refinement of polyclonal antibody production by combining oral immunization of
      chickens with harvest of antibodies from the egg yolk.
AB  - Polyclonal antibody production in mammals is generally associated with multiple
      injections of antigens and adjuvants and repeated blood sampling procedures.
      During the past 20 yr, the use of chickens instead of mammals for this purpose
      has increased. A major advantage of using birds is that the antibodies can be
      harvested from the egg yolk instead of serum, thus making blood sampling
      obsolete. In addition, the antibody productivity of an egg-laying hen is much
      greater than that of a similar sized mammal. This article focuses on the
      developments in oral immunization strategies for chickens that combined with the
      antibodies from the egg yolk, have great potential for active implementation of
      the three Rs (replacing, reducing, and refining the use of laboratory animals to
      the extent possible) in polyclonal antibody production schemes.

PMID- 15953837
TI  - Using polyclonal and monoclonal antibodies in regulatory testing of biological
      products.
AB  - Polyclonal and monoclonal antibodies are often used in regulatory testing of
      biologicals (vaccines and related products). One of the most common applications
      for antibody-based immunoassays is as a batch release test. Batch release tests,
      whether they measure serological responses to vaccination or they quantify
      individual antigens by in vitro methods, must provide an acceptable estimate of
      potency of an individual batch of vaccine. Thus, due consideration must be given
      to the type of antibody used or quantified in such assays. Differences in
      specificity and avidity may affect the utility of an assay as an indicator of
      potency; case examples are given to illustrate these concepts. Concerns
      associated with antigen quantification assays (e.g., reagent denaturation upon
      binding to solid substrates, and interference from nontarget antigens or
      additives in a complex vaccine) are also discussed. International efforts to
      harmonize test methods in recent years have increased the importance of
      establishing standardized antibodies. Sources of such antibodies and issues
      associated with the ongoing availability of antibody supplies are described.

PMID- 15953838
TI  - Industrial implementation of in vitro production of monoclonal antibodies.
AB  - Monoclonal antibodies are widely used at GlaxoSmithKline Biologicals (GSK Bio)
      for the quantification and characterization of antigens and for the release of
      vaccine lots. In 1998, GSK Bio decided to change the production of monoclonal
      antibodies (MAbs) designed for immunological tools from in vivo to in vitro
      technology. In 2004, all MAbs used at GSK Bio were produced in vitro. These MAbs
      cover more than 100 different targets with a variety of 1500 hybridomas, and
      approximately 60 to 90 MAbs are produced every year. This article describes the
      development process, including a description of the different systems tested
      based on double membrane or hollow fiber technology. The productivity, assets,
      and drawbacks of the different technologies are presented, and evaluation
      strategies for the choice of in vitro systems are discussed. Binding kinetics
      displayed by MAbs produced in vitro and in vivo were found to be similar, and
      MAbs produced in vitro are suitable tools for various immunological applications.

PMID- 15953839
TI  - Advances in monoclonal antibody technology: genetic engineering of mice, cells,
      and immunoglobulins.
AB  - The ability to produce antibodies that are directed against specific antigens has
      played a crucial role in advancing scientific discoveries. Recombinant
      technologies have extended the application of antibodies beyond the research
      laboratory and into the clinic for the treatment of cancer and other diseases.
      Creative approaches using these technologies have been used to reduce the
      antibody to its minimal functional size, and/or make them bifunctional
      (immunotoxins), bispecific, or less immunoreactive (humanized). Additionally,
      mice that are engineered to generate antibodies of human genomic origin have been
      used to produce therapeutic antibodies and are being further developed. As the
      research and clinical demands for antibodies continue to increase, the
      development of improved resources (cell lines and animals) to improve production
      efficiency, generate larger repertoires, and deliver greater yields of antibodies
      is being explored, and advances in this area are discussed further in this
      review.

PMID- 15953840
TI  - Occupational medicine in the Slovene area.
AB  - Slovenia is a small, fast developing country in the EU with approximately
      2,000,000 inhabitants and 700,000 employed. Occupational medicine has been
      present in Slovenia for as long as 500 yr. Today, 130 specialists of occupational
      medicine are in charge of health protection of the employed (including transport
      workers and athletes). There are also 1,100 safety engineers, who take care of
      the technical side of occupational safety. We are guided in our work by modern
      occupational health and safety legislation, which is based on EU directive
      89/391EEC. The average sick leave rate in Slovenia is about 4.7%, caused mostly
      by injuries, bone, muscle and connective tissue diseases and respiratory
      diseases. Sick leave appears most frequently in the textile industries and coal
      mining. Annually, around 26,000 occupational injuries (32.7 per 1,000 employed)
      and 25 fatalities (3 per 100,000 employed) occur. Most injuries occur in
      construction, manufacturing and farming. Each year there are 8,500 disablility
      cases (2,500 disability retirements-most caused by mental illnesses), but only 30
      acknowledged cases of occupational diseases (mostly occupational skin diseases,
      asthma and asbestosis). Occupational medicine in Slovenia is strongly associated
      with occupational medicine in the more developed European countries. It is
      therefore moving out of clinics and into the working environment, where its goals
      lie in primary prevention, i.e. establishing and keeping healthy working
      environments that guarantee high productivity, health and well-being of workers
      as a whole.

PMID- 15953841
TI  - Relationship between two job stress models and coronary risk factors among
      Japanese part-time female employees of a retail company.
AB  - The objective of this study was to explore the associations between two major job
      stress models (job strain and effort-reward imbalance) and coronary heart disease
      (CHD) risk factors (blood pressure; total, high- (HDL) and low-density
      lipoprotein (LDL) cholesterol; and triglycerides) in Japanese part-time female
      employees of a retail company. The study population was either 35 yr old or
      between 40 and 63 yr old. Data collection was carried out in 2002; a total of
      1,401 subjects participated in a medical examination and completed a
      questionnaire. After adjusting for other covariates (age, relative weight,
      tobacco use, alcohol consumption, lack of exercise, education, marital status,
      history of child bearing, medical treatment for disease, and occupation), a
      significant association was found between the effort-reward imbalance, a "high
      cost and low-gain" condition at work, and a high prevalence of low HDL
      cholesterol (Odds ratio=4.4). A weak but unexpected association was found between
      job strain and low prevalence of low HDL cholesterol. In explanatory analysis
      with individual components of the two models, associations were evident between
      high extrinsic effort and high prevalence of low HDL cholesterol and low
      prevalence of high triglyceride, high job control and low prevalence of high
      systolic blood pressure, and high job demands and low prevalence of high systolic
      and diastolic blood pressure. In this cross-sectional study of Japanese part-time
      working women, a significant association was found between effort-reward
      imbalance and unfavorable HDL cholesterol profiles. The findings did not support
      the hypothesis that job strain is associated with CHD risk factors.

PMID- 15953842
TI  - Lifting strengths in different horizontal distances of objects to be lifted.
AB  - This study recruited eleven healthy males and thirteen healthy females to examine
      their maximum two-handed isometric back lifting strength, upper-body lifting
      strength, arm lifting strength and shoulder lifting strength in three different
      horizontal distances of objects to be lifted (toes were anterior to, aligned
      with, and posterior to the exerted handle). The results showed that human lifting
      strength decreased significantly as the toe position shifted from anterior of the
      vertical plane of the exerted handle to posterior of the vertical plane of the
      exerted handle. The strength order relationship between back lifting strength and
      upper-body lifting strength was dependent on the horizontal distance of objects
      to be lifted. This study also observed that the effects of the horizontal
      distance of objects to be lifted on human lifting postural angles for the four
      assessed lifting types mainly occurred in the upper extremities. This study
      recommends that practitioners should not overlook the effects of the horizontal
      distance of objects to be lifted on lifting strength when evaluating workers'
      lifting strength for screening purposes.

PMID- 15953843
TI  - Occupational stress in nurses in psychiatric institutions in Taiwan.
AB  - Nurses are known to be exposed to occupational stress. However, occupational
      stress is not well documented for nurses in psychiatric institutions in Taiwan. A
      cross-sectional study was conducted to explore the work-related stress and risk
      factors of nurses in psychiatric institutions in Taiwan. A structured
      questionnaire was distributed to nurses at five state-owned psychiatric hospitals
      in Taiwan in 2001. Demographic information, working environment, and personal
      health status were inquired. Occupational stress was assessed based on the
      Chinese version of Job Content Questionnaire (JCQ). General health status and
      mental health were evaluated by the International Quality of Life Assessment
      Short Form-36 (IQOLA SF-36). A total of 573 questionnaires were disseminated to
      nurses and 518 (90.4%) were satisfactorily completed by nurses, including 408
      female full-time nurses who had been in their current work for more than 6
      months. In the past one month, 17.2% of nurses reported being under significant
      stress often or always. Assault episodes were reported by 45.1% of nurses in the
      past 6 months. Among the nurses, 16.9%, 25.2%, 50.0%, and 7.8% belong to the
      "High strain", "Low strain", "Active", and "Passive" groups, respectively.
      Perceived occupational stress was associated with young age,
      widowed/divorced/separated marital status, high psychological demand, low
      workplace support, and threat of assault at work. Lower general health score was
      associated with low job control, high psychological demand, and perceived
      occupational stress. A lower mental health score was associated with low job
      control, high psychological demand, low workplace support, and perceived
      occupational stress. We concluded that nurses in psychiatric institutions are
      under significant stress related to work factors.

PMID- 15953844
TI  - Effects of a supervisory education for positive mental health in the workplace: a
      quasi-experimental study.
AB  - Single-session supervisory education was developed in conjunction with the
      Japanese national guidelines for the promotion of employee mental health. Totally
      267 voluntary supervisors in a prefectural office were presented with
      comprehensive information on the role they had to fulfill to promote mental
      health in the workplace. Totally 864 office employees (53%) were evaluated to
      determine whether education had had an effect on their psychological distress and
      job performance. The findings from the departments in which more than one-third
      of the supervisors had attended education were compared to those from the
      departments in which no more than one-third of the supervisors had attended
      education. Three months after the education, the levels of psychological distress
      and, to a lesser extent, self-reported job performance improved among employees
      in the departments in which at least one-third of the supervisors attended the
      education compared to those from departments with lower attendance rates of the
      supervisors. For the psychological outcome, the positive educational effect was
      supported by statistically significant interaction terms between time and
      department category with adjustment for the confounders. Favorable changes were
      noted among supervisors who received the education in knowledge, attitude, and
      behavior regarding mental health practices. The behavioral changes were related
      to decreasing workplace problems and referral of employees to the liaison office
      and associated medical institutions. Despite several limitations, the findings
      suggest that providing supervisors with appropriate information has a positive
      effect on employee psychological well-being.

PMID- 15953846
TI  - A 13-week toxicity study of bismuth in rats by intratracheal intermittent
      administration.
AB  - Although bismuth is widely used as a lead substitute in the industrial field, the
      toxicity of bismuth by inhalation is little known. We performed a 13-wk
      intratracheal intermittent bismuth dose toxicity study. Bismuth was administered
      at dose levels of 0, 0.8, 4, 20 mg/kg to male Crj:CD(SD)IGS rats (SPF) by
      intratracheal intermittent administration once a week for thirteen weeks to
      investigate its potential toxic effects; especially for specific adverse effects
      and changes related to pre-neoplastic lesions. Our results showed foreign body
      inflammation in the lungs, which was caused by intratracheal administration of
      bismuth, and physical changes related to pulmonary lesions; however, there were
      no serious changes in other organs. We concluded that dose-dependent, but not
      specific adverse effects, were attributable to bismuth inhalation in the rat.

PMID- 15953845
TI  - Secular trends and geographical variations in the dietary intake of
      polybrominated diphenyl ethers (PBDEs) using archived samples from the early
      1980s and mid 1990s in Japan.
AB  - A retrospective exposure assessment among the general population for
      polybrominated diphenyl ethers (PBDEs) was conducted using dietary surveys. We
      analyzed samples of food duplicate portions collected in the early 1980s (1980
      survey: N=40) and the mid 1990s (1995 survey: N=39) from female subjects (5
      participants from each of 8 sites per survey except for one site) living
      throughout Japan, from the north (Hokkaido) to the south (Okinawa). The study
      populations in the 1980 and 1995 surveys were different, but lived in the same
      communities. We measured four PBDE congeners [2,2',4,4'-tetrabrominated diphenyl
      ether (tetraBDE): #47; 2,2',4,4',5-pentaBDE: #99; 2,2',4,4',6-pentaBDE: #100; and
      2,2',4,4',5,5'-hexaBDE: #153] in the diet. #99 was the most abundant congener in
      the diet (49% of the total PBDEs), followed by #47 (33%), #100 (12%) and #153
      (6%). Regional variations found in the 1980 survey decreased in the 1995 survey.
      The total daily intake of PBDEs (ng/d) [GM (GSD)] in the 1980 survey [91.4 (4.1)]
      was not significantly different from that in the 1995 survey [93.8 (3.4)] for the
      total population, nor did it differ among the sites including Shimane, in which a
      20-fold increase in serum concentrations was observed in the same population1).
      In consideration of the significant increases in the serum concentration,
      inhalation may be more important than food ingestion as the route of human
      exposure to PBDEs.

PMID- 15953847
TI  - Thirteen-week inhalation toxicity of p-dichlorobenzene in mice and rats.
AB  - Subchronic inhalation toxicity of p-dichlorobenzene (p-DCB) was examined by
      exposing BDF1 mice and F344 rats of both sexes (6 h/d and 5 d/wk) to inhalation
      of 25, 55, 120, 270 or 600 ppm (v/v) p-DCB vapor for 13 wk. The exposure to p-DCB
      vapor retarded the growth rate in the male mice, and induced hepatotoxicity in
      the mice and rats of both sexes and renal and hematological toxicity in the male
      rats. Hepatotoxicity was characterized by increased liver weight, hepatocellular
      hypertrophy, and increased serum levels of total cholesterol. Liver necrosis and
      increased serum levels of AST and ALT were observed in the exposed mice, whereas
      these changes, which indicate hepatocellular death, did not occur in any of the
      exposed rats. p-DCB-induced renal lesions occurred only in the male rats. Hyaline
      droplets were observed in the proximal tubular epithelial cells, and were stained
      positively with anti-alpha2u-globulin, suggesting excessive accumulation of
      alpha2u-globulin in the epithelial cells. Granular casts were formed in the
      tubular lumen, resulting from the necrotic desquamation of the renal tubular
      epithelium. Papillary mineralization in the renal pelvis and increased serum
      levels of BUN and creatinine were noted. These renal changes indicated alpha2u
      globulin nephropathy. Decreases in red blood cell counts, hemoglobin
      concentration, hematocrit and mean corpuscular volume and increased spleen weight
      occurred in the exposed male rats. The NOAEL was 120 ppm for the hepatic endpoint
      in mice and for the renal endpoint in rats. The maximum tolerated dose for a 2-yr
      bioassay inhalation study of rodent carcinogenicity was estimated to be 300 ppm,
      based on the present results.

PMID- 15953848
TI  - The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair
      enzymes.
AB  - Nitropyrenes (NPs) present in diesel and gasoline emissions are mutagenic and
      carcinogenic in experimental animals. Nitro-reduction of 1-NP causes oxidative
      stress. It is unclear whether 8-hydroxydeoxyguanosine (8-OH-dG) is produced from
      1-NP and whether it contributes to the carcinogenic activity of 1-NP. In this
      study, we measured the level of reactive oxygen species (ROS) in cultured human
      lung epithelial cells after exposure to 1-NP and the intracellular level of 8-OH
      dG and expression level of the 8-OH-dG repair enzymes. As results, 1-NP induced
      the generation of 8-OH-dG via ROS, but 8-OH-dG repair enzymes prevented an
      increase of 8-OH-dG formation in cellular DNA of the A549 cell line below 250
      microM of 1-NP. These data suggest that 1-NP can induce oxidative DNA damage by
      generation of ROS, which may play a role in the carcinogenesis induced by 1-NP.
      These data also suggest that individuals with impaired DNA repair enzymes might
      be more susceptible to lung cancer induced by 1-NP.

PMID- 15953849
TI  - Chaos of vowel /a/ in Japanese patients with depression: a preliminary study.

PMID- 15953850
TI  - An integrated approach for improving occupational health and safety management:
      the voluntary protection program in Taiwan.
AB  - A voluntary compliance program for occupational health and safety management,
      Voluntary Protection Programs (VPP), was implemented with a strategy of
      cooperation and encouragement in Taiwan. Due to limitations on increasing the
      human forces of inspection, a regulatory-based guideline addressing the essence
      of Occupational Health and Safety Management Systems (OHSMS) was promulgated,
      which combined the resources of third parties and insurance providers to accredit
      a self-improving worksite with the benefits of waived general inspection and a
      merit contributing to insurance premium payment reduction. A designated institute
      accepts enterprise's applications, performs document review and organizes the
      onsite inspection. A final review committee of Council of Labor Affairs (CLA)
      confers a two-year certificate on an approved site. After ten years, the efforts
      have shown a dramatic reduction of occupational injuries and illness in the total
      number of 724 worksites granted certification. VPP worksites, in comparison with
      all industries, had 49% lower frequency rate in the past three years. The
      severity rate reduction was 80% in the same period. The characteristics of Taiwan
      VPP program and international occupational safety and health management programs
      are provided. A Plan-Do-Check-Act management cycle was employed for pursuing
      continual improvements to the culture fostered. The use of a quantitative
      measurement for assessing the performance of enterprises' occupational safety and
      health management showed the efficiency of the rating. The results demonstrate
      that an employer voluntary protection program is a promising strategy for a
      developing country.

PMID- 15953851
TI  - The medical science research and development supported by the Korea Science and
      Engineering Foundation.
AB  - This study examined ways of promoting research in the medical sciences by
      evaluating trends in research funding, and the present status of research funding
      by the Korea Science and Engineering Foundation (KOSEF). This study analyzed
      statistics from KOSEF from 1978 to 2003 to examine support for research. In
      medical science field, group-based programs receive more funding than do
      individual-based programs. The proportion of research funds allocated to the
      medical sciences has increased markedly each year. Researchers in the medical
      sciences have submitted more articles to Science Citation Index (SCI) journals
      than to non-SCI journals, relative to other fields. Researchers supported by the
      Mission-Oriented Basic Grants program have published the majority of these
      papers, followed by those supported by the Programs for Leading Scientists,
      Regional Scientists, Leading Women Scientists, Young Scientists, and Promising
      Women Scientists, in that order. Funding by KOSEF reflects many decades of
      government support for research and development, the development and maintenance
      of necessary infrastructure, and the education and training of medical
      scientists.

PMID- 15953852
TI  - Genetic and environmental influences on birthweight in a sample of Korean twins.
AB  - This study is the first report of genetic and environmental influences on
      birthweight using Korean twins. The sample consisted of 255 monozygotic (MZ) and
      178 dizygotic (DZ) twin pairs drawn from the Seoul Twin Family Study. Intraclass
      twin correlations were computed for the twins' birthweights obtained from parents
      (typically mothers) of the twins. To estimate genetic and shared and nonshared
      environmental influences on birthweight, standard univariate model-fitting
      analyses were performed using a software, Mx. For each gender, MZ twin
      correlations were higher than DZ twin correlations, suggesting existence of
      genetic influences on birthweight; however, DZ twin correlations were higher than
      half the MZ twin correlations, indicating that shared environmental factors are
      also important. For each zygosity, twin correlations were not significantly
      different between males and females, implicating that genes and environments that
      cause individual differences in birthweight may not vary between males and
      females. Model-fitting analyses based on the data pooled across gender yielded
      estimates of 17% for genetic, 60% for shared environmental, and 23% for nonshared
      environmental influences on birthweight.

PMID- 15953853
TI  - The effect of apolipoprotein E polymorphism on lipid levels in Korean adults.
AB  - The aim of this study was to determine the effects of polymorphisms in the
      apolipoprotein E gene (APOE) on lipid levels in Korean adults and to investigate
      the interactions between these polymorphisms and environmental factors in
      determining lipid levels. We performed a cross-sectional study of 1,900 subjects
      (668 men and 1,232 women; 45-74 yr old) in Namwon, Korea, in 2004. APOE
      polymorphisms were determined by polymerase chain reaction and restriction enzyme
      analysis. Carriers of the APOE*E2 (E2) allele had significantly lower total
      cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations than
      did carriers of the APOE*E3 (E3) or APOE*E4 (E4) alleles, regardless of gender.
      The APOE allele type had significant effect on high-density lipoprotein
      cholesterol (HDL-C) and triglyceride levels in women, but not in men. The effect
      of APOE allele type on HDL-C levels was modified by age in women. In addition, in
      men, the effect of APOE allele type on triglyceride levels was modified by
      smoking. These findings highlight the important effect of gene-environment
      interactions on lipid levels.

PMID- 15953854
TI  - Polymorphisms of high-affinity IgE receptor and histamine-related genes in
      patients with ASA-induced urticaria/angioedema.
AB  - The pathogenic mechanism of ASA-induced urticaria/angioedema (AIU) is still
      poorly understood, but it has been known that histamine releasing by cutaneous
      mast cell activation is considered to be an important role. Considering the
      importance of histamine in AIU, we speculated that a genetic abnormality of
      histamine-related genes such as a high-affinity IgE receptor, a metabolic enzyme
      of histamines and histamine receptors, may be involved in the development of AIU.
      Enrolled in the study were 110 patients with AIU, 53 patients without ASA
      hypersensitivity who had various drug allergies presenting as exanthematous skin
      symptoms, and 99 normal healthy controls (NC). Eleven single nucleotide
      polymorphisms (SNPs) of the beta chain of the high-affinity IgE receptor (FCER1B)
      and three histamine-related genes-histamine N-methyltransferase (HNMT), histamine
      H1 receptor (HRH1), histamine H2 receptor (HRH2)-were screened using the SNP-IT
      assay based on a single base extension method. No significant differences were
      observed in allele and genotype frequencies, and haplotype frequencies of all the
      SNPs of FCER1B, HNMT, HRH1, and HRH2 among the three groups (p>0.05,
      respectively). These results suggest that the polymorphisms of FCER1B and the
      three histamine-related genes may not contribute to the development of AIU
      phenotype in the Korean population.

PMID- 15953855
TI  - Distribution of the ankle-brachial index and associated cardiovascular risk
      factors in a population of middle-aged and elderly koreans.
AB  - The Doppler ankle-brachial pressure index (ABI) is an objective and efficient
      tool that can be used to determine the presence and severity of peripheral
      arterial disease in the lower extremities. The ABI value is inversely associated
      with other cardiovascular risk factors. To date, there have been no studies of
      the distribution of ABI in Korea. We performed a cross-sectional study of 1,943
      subjects (681 men and 1,262 women; 45-74 yr old) in Namwon, Korea. The prevalence
      of a low ABI (<0.90) was 2.2% in men and 1.8% in women, and a high ABI (>or=1.30)
      was prevalent in 3.1% of men and 0.8% of women. Age, smoking habits, waist
      circumference, hypertension, and blood pressure were associated with ABI values
      in both sexes. The presence of carotid plaques was associated with ABI values
      only in men, whereas pulse pressure was associated with ABI values only in women
      (p<0.05). Although the prevalence of a low ABI in the present study was lower
      than those reported previously for Western populations and Japanese men, our
      results suggest that the ABI might be used as an indicator of cardiovascular risk
      factors in adult Koreans.

PMID- 15953856
TI  - Relations of plasma high-sensitivity C-reactive protein to various cardiovascular
      risk factors.
AB  - This study was performed to evaluate the relation of high-sensitivity C-reactive
      protein (hsCRP) with several cardiovascular risk factors such as age, blood
      pressure, smoking habit and serum lipids, body mass index, blood glucose, regular
      exercise, alcohol drinking, white blood cell counts in a cross-sectional survey.
      Plasma hsCRP was measured by immunoturbidimetry in 202 subjects, aged over 50 yr,
      who participated in health-check survey in a rural area of Jeollanamdo, Korea.
      Plasma hsCRP level was 1.9 +/- 3.0 mg/dL. There were significant associations
      between hsCRP levels and age, white blood cell counts, blood glucose, diastolic
      blood pressure, HDL-cholesterol, body mass index and smoking status. In stepwise
      multivariate regression analysis, white blood cell counts, age, blood glucose,
      smoking status and body mass index were independent correlates of hsCRP levels.
      In conclusion, plasma hsCRP levels were associated with several cardiovascular
      risk factors, and these data are compatible with the hypothesis that CRP levels
      may be a marker for preclinical cardiovascular disease. Further what we need now
      are prospective studies to evaluate the association of C-reactive protein
      concentrations with subsequent cardiac events.

PMID- 15953857
TI  - Relationship between dendritic cells and activated eosinophils in induced sputum
      of asthmatics.
AB  - It has been suggested that dendritic cells (DCs) are critical antigen presenting
      cells for eosinophilic airway inflammation in a mouse model of asthma, and
      cysteinyl leukotrienes may play a role in DC trafficking in asthmatics. We
      investigated whether the number of DCs is increased in the induced sputum of both
      atopic and nonatopic asthmatics and is related to activated eosinophil count in
      the sputum. Sputum was induced by inhalation of hypertonic saline in 9 atopic and
      12 nonatopic asthmatics and 10 nonatopic normal controls, and differential cell
      counts were performed. DCs and activated eosinophils were identified by
      immunocytochemistry with monoclonal antibodies (anti-CD1a and EG2, respectively).
      There were significantly higher percentages of eosinophils, EG2+ cells, and CD1a+
      DC in the sputum of atopic and nonatopic asthmatics compared with normal
      controls, respectively. In asthmatics, the percentage of CD1a+ DC was
      significantly correlated with that of EG2+ cells (Rs=0.62, p=0.004). We
      demonstrated that the increased number of DCs was evident in the induced sputum
      of both atopic and nonatopic asthmatics, and the DC number was related to the
      activated eosinophil count, which suggests that DCs may contribute to the ongoing
      eosinophilic inflammation in asthmatic airways, and vice versa.

PMID- 15953858
TI  - Pharaoh ant (Monomorium pharaonis): newly identified important inhalant allergens
      in bronchial asthma.
AB  - The nonstinging house ant, Monomorium pharaonis (pharaoh ant), was recently
      identified as a cause of respiratory allergy. This study was performed to
      evaluate the extent of sensitization to pharaoh ant, and its clinical
      significance in asthmatic patients. We carried out skin prick tests in 318
      patients with asthma. Specific IgE (sIgE) to pharaoh ant was measured by ELISA,
      and cross-reactivity was evaluated by ELISA inhibition tests. Bronchial
      provocation testing was performed using pharaoh ant extracts. Fifty-eight (18.2%)
      of 318 patients showed positive skin responses to pharaoh ant, and 25 (7.9%) had
      an isolated response to pharaoh ant. Positive skin responses to pharaoh ant were
      significantly higher among patients with non-atopic asthma than among those with
      atopic asthma (26.0% vs. 14.9%, p<0.05). There was significant correlation
      between sIgE level and skin responses to pharaoh ant (rho=0.552, p<0.001). The
      ELISA inhibition tests indicated that pharaoh ant allergens had various pattern
      of cross-reactivity to house dust mites and cockroaches. Bronchial provocation
      tests to pharaoh ant were conducted for 9 patients, and eight showed typical
      asthmatic reactions. In conclusion, pharaoh ant is an important source of
      aeroallergens, and it should be included in the skin test battery for screening
      the causative allergens in patients with asthma.

PMID- 15953859
TI  - Scoring method for early prediction of neonatal chronic lung disease using
      modified respiratory parameters.
AB  - In our previous study, we have demonstrated that peak inspiratory pressure over
      birth weight (PIP/kg) and mean airway pressure over birth weight (MAP/kg) were
      more significant risk factors for the development of neonatal chronic lung
      disease (CLD) than PIP and MAP. We aimed to develop a scoring method using the
      modified respiratory variables (SMUMRV) to predict CLD at early postnatal period.
      From 1997 to 1999, a retrospective review was performed for 197 infants <1,500 g
      for the development of the SMUMRV based on statistical analysis. From 2000 to
      2001, calculated scores on day 4, 7 and 10 of life were obtained prospectively
      for 107 infants <1,500 g. Predictive values and the area under the receiver
      operator characteristic curve (AUC) were determined and compared with the result
      of the previous regression model. Gestational age, birth weight, 5 min Apgar
      score, PIP/kg at 12 hr of age, fractional inspired oxygen (FiO2), MAP/kg,
      modified oxygenation index and ventilatory mode were selected as parameters of
      SMUMRV. No significant differences of AUCs were found between the SMUMRV and the
      Yoder model. It is likely that our scoring method provides reliable values for
      predicting the development of CLD in very low birth weight infants.

PMID- 15953860
TI  - Lung cancer screening with low-dose helical CT in Korea: experiences at the
      Samsung Medical Center.
AB  - To determine overall detection rates of lung cancer by low-dose CT (LDCT)
      screening and to compare histopathologic and imaging differences of detected
      cancers between high- and low-risk groups, this study included 6,406 asymptomatic
      Korean adults with >or=45 yr of age who underwent LDCT for lung cancer screening.
      All were classified into high- (>or=20 pack-year smoking; 3,353) and low-risk
      (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of
      detected cancers and detection rates between high- and low-risk. At initial CT,
      35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer
      detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers
      appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer
      likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of
      23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215).
      Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic
      Korean population with detection rate of 0.36% on a population basis and may be
      useful for discovering early lung cancer in low-risk group as well as in high
      risk group.

PMID- 15953861
TI  - Direct and indirect effects of androgens on survival of hematopoietic progenitor
      cells in vitro.
AB  - Androgens remain a common treatment for certain type of anemia, based upon its
      myelostimulating effects; however, it has not been established whether androgens
      affect apoptosis of hematopoietic progenitor cells (HPCs). We investigated the
      effects of the androgens, such as testosterone, 5beta-dihydrotestosterone (5
      DHT), and oxymetholone, on apoptosis of normal hematopoietic progenitor cells in
      vitro. Androgens did not rescue normal bone marrow (BM) CD34+ cells and colony
      forming cells (CFCs), other than mature erythroid CFCs, from apoptosis induced by
      serum- and growth factor deprivation. Oxymetholone did not affect growth factor
      mediated survival of normal CD34+ cells or its inhibition by interferon-gamma
      (IFN-gamma). In a standard methylcellulose clonogenic assay, low concentrations
      of oxymetholone and 5-DHT stimulated the clonal growth of colony-forming unit
      (CFU)-erythroid, but did not affect growth of CFU-granulocyte/macrophage or burst
      forming unit-erythroid. Oxymetholone and 5-DHT stimulated the production of stem
      cell factor in normal bone marrow stromal cells (BMSCs) via transcriptional
      regulation. In agreement with this, oxymetholone-treated BMSCs better supported
      the survival of HPCs. These data indicate that survival-enhancing or growth
      stimulatory effects of androgens on hematopoietic progenitor cells are minimal
      and mostly restricted to mature erythroid progenitors, and its myelostimulating
      effects could be attributed, at least in part, to the stimulation of production
      of hematopoietic growth factors in BMSCs.

PMID- 15953862
TI  - Prognostic factors of response to laparoscopic splenectomy in patients with
      idiopathic thrombocytopenic purpura.
AB  - Laparoscopic splenectomy (LS) has become the treatment of choice for patients
      with idiopathic thrombocytopenic purpura (ITP) who do not respond to medical
      treatment. The aim of this study was to identify factors predictive of outcome
      after LS for ITP. From May 1997 to December 2002, we performed 30 LS on patients
      with ITP. A positive response was defined as a postoperative platelet count
      greater than 50,000/micro L and no requirement for maintenance therapy. Chi
      square testing was performed to determine the predictive effects of the following
      variables: age, sex, preoperative response to steroids or immunoglobulin,
      duration of disease, antiplatelet antibody, platelet associated antibody, and
      antinuclear antibody. LS was successfully performed in all patients. For a mean
      follow-up interval of 24.3 months, response to LS was 73.3%. Splenectomy for
      steroid nonresponders resulted in an inferior complete response rate (10 of 18,
      55.6%) as compared with those that experienced relapse after steroid treatment
      (11 of 12, 91.7%) (p=0.042). The other significant predictor of outcome by
      univariate analysis was the time between diagnosis and surgery (p=0.049). The
      other variables showed no significant correlation with successful splenectomy. We
      conclude that LS can be performed safely with a satisfactory remission rate in
      patients with ITP who do not respond to medical treatment, and that the factors
      most frequently associated with surgical success are a response to steroid and
      disease duration.

PMID- 15953863
TI  - Hypoadiponectinemia and insulin resistance are associated with nonalcoholic fatty
      liver disease.
AB  - We investigated the association between nonalcoholic fatty liver disease (NAFLD)
      and plasma adiponectin levels and insulin resistance. We recruited study subjects
      among one hundred and eighty one persons who were examined abdominal ultrasound
      at routine screening tests. A standard interview (consumption of alcohol and
      medical history), physical examination (height, weight, waist circumference, and
      blood pressure), and biochemical study (lipid parameters, aminotransferases,
      fasting plasma glucose, fasting insulin, and plasma adiponectin) were performed.
      Subjects who consumed alcohol more than moderate, evidence of viral hepatitis,
      toxic hepatitis, and serious cardiac, renal, or hepatic disease were excluded.
      Thirty-eight NAFLD patients and 53 control subjects diagnosed by ultrasound were
      finally analyzed. The plasma adiponectin level was significantly correlated with
      HDL-cholesterol (r=0. 38, p<0.001), triglycerides (r=-0.22, p=0.04), fasting
      insulin (r=-0.37, p<0.01), and insulin resistance by homeostasis model of
      assessment-insulin resistance (HOMAIR) (r=-0.39, p<0.01), after adjusting for
      age, sex, and adiposity. Multiple logistic regression analysis indicated that
      HOMA-IR was a significant predictor of having NAFLD (odds ratio [OR]=2.38; 95%
      confidence interval [CI]: 1.52-5.74), while adiponectin had a protective effect
      against NAFLD (OR=0.22; 95% CI: 0.09-0.55). We demonstrated that
      hypoadiponectinemia and insulin resistance are associated with NAFLD independent
      of obesity.

PMID- 15953864
TI  - An experimental animal model of fulminant hepatic failure in pigs.
AB  - The objective of this study was to develop an experimental animal model of
      fulminant hepatic failure to test the efficacy of the bioartificial liver system.
      The portal vein and the hepatic artery were clamped intermittently and then the
      hepatic artery was ligated (ligation group, n=5). Pigs whose hepatic arteries
      were not ligated after clamping were assigned to the non-ligation group (n=5).
      The biochemical changes in blood, histologic alterations of the liver and
      neurologic examination for pigs were checked up. All animals died within 17 hr in
      the ligation group. On the other hand, all animals survived more than 7 days in
      the non-ligation group. In the ligation group, the levels of ammonia, lactic acid
      and creatinine showed a progressively increasing pattern. Prothrombin time was
      also prolonged gradually. Cytoplasmic condensation and nuclear pyknosis of
      hepatocytes were detected histologically at autopsy. Neurologic findings such as
      decreased pain sensation, tachypnea and no light reflex of pupils were observed.
      The findings shown in the ligation group are similar to the clinical features of
      fulminant hepatic failure in human and this animal model is reproducible.
      Therefore, this can be a suitable animal model to evaluate the efficacy of the
      bioartificial liver system for treating fulminant hepatic failure.

PMID- 15953865
TI  - Overlapping gene mutations of hepatitis B virus in a chronic hepatitis B patient
      with hepatitis B surface antigen loss during lamivudine therapy.
AB  - Disappearance of hepatitis B surface antigens (HBsAg) in chronic hepatitis B
      usually indicates clearance of hepatitis B virus (HBV) infection. However, false
      HBsAg negativity with mutations in pre-S2 and 'a' determinant has been reported.
      It is also known that YMDD mutations decrease the production of HBV and escape
      detection of serum HBsAg. Here, we report overlapping gene mutations in a patient
      with HBsAg loss during the lamivudine therapy. After 36 months of lamivudine
      therapy in a 44-yrold Korean chronic hepatitis B patient, serum HBsAg turned
      negative while HBV DNA remained positive by a DNA probe method. Nucleotide
      sequence of serum HBV DNA was compared with the HBV genotype C subtype adr
      registered in NCBI AF 286594. Deletion of nucleotides 23 to 55 (amino acids 12 to
      22) was identified in the pre-S2 region. Sequencing of the 'a' determinant
      revealed amino acid substitutions as I126S, T131N, M133T, and S136Y. Methionine
      of rtM204 in the P gene was substituted for isoleucine indicating YIDD mutation
      (rtM204I). We identified a HBV mutant composed of pre-S2 deletions and 'a'
      determinant substitutions with YMDD mutation. Our result suggests that false
      HBsAg negativity can be induced by combination of overlapping gene mutations
      during the lamivudine therapy.

PMID- 15953866
TI  - The effect of simvastatin on the proliferation and differentiation of human bone
      marrow stromal cells.
AB  - Statins have been postulated to affect the bone metabolism. Recent experimental
      and epidemiologic studies have suggested that statins may also have bone
      protective effects. This study assessed the effects of simvastatin on the
      proliferation and differentiation of human bone marrow stromal cells (BMSCs) in
      an ex vivo culture. The bone marrow was obtained from healthy donors. Mononuclear
      cells were isolated and cultured to osteoblastic lineage. In the primary culture,
      10(-6) M simvastatin diminished the mean size of the colony forming units
      fibroblastic (CFU-Fs) and enhanced matrix calcification. At near confluence, the
      cells were sub-cultured. Thereafter, the alkaline phosphatase (ALP) activities of
      each group were measured by the time course of the secondary culture. Simvastatin
      increased the ALP activity in a dose dependent manner, and this stimulatory
      effect was more evident during the early period of culture. A 3-[4, 5
      dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was performed
      during the secondary culture in order to estimate the effect of simvastatin on
      the proliferation of human BMSCs. When compared to the control group, simvastatin
      significantly decreased the proliferation of cells of each culture well. 10(-6) M
      of simvastatin also significantly enhanced the osteocalcin mRNA expression level.
      This study shows that simvastatin has a stimulatory effect on bone formation
      through osteoblastic differentiation, and has an inhibitory effect on the
      proliferative potential of human BMSCs.

PMID- 15953867
TI  - Development of anthropometry-based equations for the estimation of the total body
      water in Koreans.
AB  - For developing race-specific anthropometry-based total body water (TBW)
      equations, we measured TBW using bioelectrical impedance analysis (TBW(BIA)) in
      2,943 healthy Korean adults. Among them, 2,223 were used as a reference group.
      Two equations (TBW(K1) and TBW(K2)) were developed based on age, sex, height, and
      body weight. The adjusted R2 was 0.908 for TBW(K1) and 0.910 for TBW(K2). The
      remaining 720 subjects were used for the validation of our results. Watson
      (TBW(W)) and Hume-Weyers (TBW(H)) formulas were also used. In men, TBW(BIA)
      showed the highest correlation with TBW(H), followed by TBW(K1), TBW(K2) and
      TBW(W). TBW(K1) and TBW(K2) showed the lower root mean square errors (RMSE) and
      mean prediction errors (ME) than TBW(W) and TBW(H). On the Bland-Altman plot, the
      correlations between the differences and means were smaller for TBW(K2) than for
      TBW(K1). On the contrary, TBW(BIA) showed the highest correlation with TBW(W),
      followed by TBW(K2), TBW(K1), and TBW(H) in females. RMSE was smallest in TBW(W),
      followed by TBW(K2), TBW(K1) and TBW(H). ME was closest to zero for TBW(K2),
      followed by TBW(K1), TBW(W) and TBW(H). The correlation coefficients between the
      means and differences were highest in TBW(W), and lowest in TBW(K2). In
      conclusion, TBW(K2) provides better accuracy with a smaller bias than the TBW(W)
      or TBW(H) in males. TBW(K2) shows a similar accuracy, but with a smaller bias
      than TBW(W) in females.

PMID- 15953868
TI  - Identification of proteins differentially expressed in the conventional renal
      cell carcinoma by proteomic analysis.
AB  - Renal cell carcinoma (RCC) is one of the most malignant tumors in urology, and
      due to its insidious onset patients frequently have advanced disease at the time
      of clinical presentation. Thus, early detection is crucial in management of RCC.
      To identify tumor specific proteins of RCC, we employed proteomic analysis. We
      prepared proteins from conventional RCC and the corresponding normal kidney
      tissues from seven patients with conventional RCC. The expression of proteins was
      determined by silver stain after two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE). The overall protein expression patterns in the RCC and
      the normal kidney tissues were quite similar except some areas. Of 66
      differentially expressed protein spots (p<0.05 by Student t-test), 8 different
      proteins from 11 spots were identified by MALDI-TOF-MS. The expression of the
      following proteins was repressed (p<0.05); aminoacylase-1, enoyl-CoA hydratase,
      aldehyde reductase, tropomyosin alpha-4 chain, agmatinase and ketohexokinase. Two
      proteins, vimentin and alpha-1 antitrypsin precursor, were dominantly expressed
      in RCC (p<0.05).

PMID- 15953869
TI  - Identification of new proteins in follicular fluid from mature human follicles by
      direct sample rehydration method of two-dimensional polyacrylamide gel
      electrophoresis.
AB  - Human follicular fluid (HFF) includes various biologically active proteins which
      can affect follicle growth and oocyte fertilization. Thus far, these proteins
      from mature follicles in human follicular fluid have been poorly characterized.
      Here, two-dimensional polyacrylamide gel electrophoresis (2-DE) with matrix
      assisted laser desorption/ionization-mass spectrometry (MALDI-MS) was used to
      identify new proteins in HFF. Mature follicular fluids were obtained from five
      females after oocyte collection during in vitro fertilization (IVF). We directly
      rehydrated HFF samples, obtained high-resolution 2-DE maps, and processed them
      for 2-DE and MALDI-MS. One hundred eighty spots were detected and 10 of these
      spots were identified. By the 2-DE database, six of them had been reported, as
      proteins already existing in HFF. Hormone sensitive lipase (HSL), Unnamed protein
      product 1 (UPP1), Unnamed protein product 2 (UPP2), and apolipoprotein A-IV
      precursor were newly detected. HSL and apolipoprotein A-IV participate in lipid
      metabolism. UPP1 has a homology with selenocysteine lyase. We found by RT-PCR
      that these genes are expressed from human primary granulosa cells. The proteins
      identified here may emerge as potential candidates for specific functions during
      folliculogenesis, hormone secretion regulation, or oocyte maturation. Further
      functional analysis of these proteins is necessitated to determine their
      biological implications.

PMID- 15953870
TI  - Clinical effectiveness of urinary human chorionic gonadotropin related protein
      (hCGRP) quantification for diagnosis of ectopic pregnancy.
AB  - We detected pregnancy related new molecule, human chorionic gonadotropin related
      protein (hCGRP) in the urine of a pregnant women by using a monoclonal antibody
      against the human chorionic gonadotropin (hCG). This study examined the
      effectiveness of urinary hCGRP quantification in diagnosing ectopic pregnancy.
      This study included 40 normal pregnant women and 25 patients with ectopic
      pregnancy. Patients' serum and urinary intact whole hCG (i-hCG) and hCGRP
      concentrations were measured using sandwich ELISA and the ratio of hCGRP to i-hCG
      was calculated. Statistical analysis was performed using statistical package for
      social sciences (SPSS) 10.0. Receiver operating characteristic (ROC) curve
      analysis was performed to evaluate the cut-off value to discriminate ectopic
      pregnancies from normal intrauterine pregnancies. Urinary hCGRP and hCGRP/i-hCG
      ratio in ectopic pregnancy group (14 +/- 6.6 ng/mL, 4.6 +/- 1.9%, respectively)
      were significantly lower than those of normal pregnancy group (149 +/- 10.2
      ng/mL, 29.7 +/- 1.9%, respectively; p<0.001). Based on ROC curve analysis, a cut
      off point of urinary hCGRP/i-hCG ratio <16.2% discriminated between ectopic
      pregnancy and normal pregnancy with a sensitivity, specificity, positive
      predictive value and negative predictive value of 92.0%, 90.0%, 32.6%, and 99.5%,
      respectively. Urinary hCGRP/i-hCG ratio measurement may be effective in
      diagnosing ectopic pregnancy.

PMID- 15953871
TI  - Selected adnexal cystic masses in postmenopausal women can be safely managed by
      laparoscopy.
AB  - The aim of this study was to assess the efficacy and safety of laparoscopic
      treatment for adnexal cystic masses that were predicted to be benign in
      postmenopausal women. Postmenopausal women found to have an adnexal cystic mass
      were retrospectively evaluated with transvaginal ultrasonography, and serum CA
      125 levels. The selection criteria were adnexal cystic masses greater than 3 cm
      but less than 10 cm, the masses were in the benign range (4-8) of Sassone's
      scoring system for transvaginal ultrasonography, and the patients had serum CA
      125 levels less than 65 IU/mL. Two hundred nineteen women fulfilled the criteria
      and underwent operative laparoscopy. Almost all the masses (99.5%) were
      accurately predicted to be benign except for one borderline ovarian tumor. Two
      hundreds thirteen (97.3%) women were successfully managed by operative
      laparoscopy and six (2.7%) required laparotomy. For the patients managed by
      laparoscopy, the mean operative time was 51.3 min; the mean hospital stay was 2.5
      days. There was no significant morbidity and surgery-related mortality. The
      combination of the Sassone's scoring system for transvaginal ultrasonography and
      serum CA-125 level can accurately predict benign cystic masses, and operative
      laparoscopy is technically feasible and safe for the management of adnexal mass
      in postmenopausal women.

PMID- 15953873
TI  - Tissue engineered vascularized bone formation using in vivo implanted osteoblast
      polyglycolic acid scaffold.
AB  - Repair of skeletal defects with vascularized bone grafts has many advantages over
      non-vascularized free grafts, but the availability of these grafts is extremely
      limited. This study was designed to determine whether new vascularized bone could
      be engineered by transplantation of osteoblasts around existing vascular pedicles
      using biodegradable, synthetic polymer as a cell delivery vehicle. Cells were
      isolated from the periosteum of fetal bovine humerus, and then seeded onto non
      woven multifilament, polyglycolic acid polymer. The polymers provided three
      dimensional support during in vitro culture. The cell-polymer constructs were
      maintained in vitro for two weeks and then implanted around the right femoral
      vessels of twelve athymic nude rats. The polymer templates without the cells were
      implanted around left femoral vessels of each mouse as a control. Twelve rats
      were sacrificed at the following intervals: three rats at six,and nine rats at
      nine weeks. New bone formation was evident in 10 out of the 12 periosteal-derived
      cell seeded implants. At six weeks, the tissue was primarily composed of what
      appeared both grossly and histologically to be cartilage enveloping small islands
      of osteoid. The degree of osteoid and bone formation progressed with time, as
      blood vessels invaded the tissue. This tissue ultimately underwent morphogenesis
      to become an organized trabeculated bone with a vascular pedicle. We believe that
      this technique may prove to be useful in the reconstruction of bony defect.

PMID- 15953872
TI  - Diagnostic performances of anti-cyclic citrullinated peptides antibody and
      antifilaggrin antibody in Korean patients with rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology.
      We studied the diagnostic performances of anti-cyclic citrullinated peptides
      antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody
      (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in
      Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared
      with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA
      assays were performed in 324 RA patients, 251 control patients, and 286 healthy
      subjects. The optimal cut off values of each assay were determined at the maximal
      point of area under the curve by receiver-operator characteristics (ROC) curve.
      Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of
      AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a
      sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed
      positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In
      conclusion, we consider that anti-CCP could be very useful serological assay for
      the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than
      RF and AFA at the optimal cut off values and could be performed by easy,
      convenient ELISA method.

PMID- 15953874
TI  - Development of Korean standard brain templates.
AB  - We developed age, gender and ethnic specific brain templates based on MR and
      Positron-Emission Tomography (PET) images of Korean normal volunteers. Seventy
      eight normal right-handed volunteers (M/F=49/29) underwent 3D T1-weighted SPGR MR
      and F-18-FDG PET scans. For the generation of standard templates, an optimal
      target brain that has the average global hemispheric shape was selected for each
      gender. MR images were then spatially normalized by linear transformation to the
      target brains, and normalization parameters were reapplied to PET images.
      Subjects were subdivided into 2 groups for each gender: the young/midlife (<55
      yr) and the elderly groups. Young and elderly MRI/PET templates were composed by
      averaging the spatially normalized images. Korean templates showed different
      shapes and sizes (mean length, width, and height of the brains were 16.5, 14.3
      and 12.1 cm for man, and 15.6, 13.5 and 11.4 cm for woman) from the template
      based on Caucasian (18.3, 14.2, and 13.3 cm). MRI and PET templates developed in
      this study will provide the framework for more accurate stereotactic
      standardization and anatomical localization.

PMID- 15953875
TI  - Clinical significance of Ki-67 labeling index in pituitary macroadenoma.
AB  - The aim of our study was to investigate the correlation of the proliferative
      activity of pituitary neoplasms with clinical characteristics and recurrences.
      Tumor specimens were obtained from 44 consecutive patients with pituitary
      macroadenomas who underwent surgery between July 1998 and August 2003. Specimens
      were immediately fixed in 10% buffered formalin and then embedded in paraffin.
      The Ki-67 antigen was assessed by immumohistochemical analysis using the
      monoclonal antibody. We investigated the correlation of the Ki-67 labeling index
      with the following clinical and radiological characteristics: sex, age, presence
      or absence visual field defect, tumor classification, maximal tumor diameter,
      Hardy's classification, type of tumor, invasiveness, and recurrence. Our study
      suggests that the clinical characteristics such as visual field defect and
      recurrence are correlated with the high Ki-67 labeling index. No statistical
      differences were observed in the Ki-67 labeling index in relation to the
      following characteristics: sex, age, tumor classification, maximal tumor
      diameter, Hardy's classification, type of tumor, and invasiveness into the
      sphenoid sinus or cavernous sinus.

PMID- 15953876
TI  - Association of vitamin D receptor gene polymorphism and Parkinson's disease in
      Koreans.
AB  - 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), which is the biologically active
      form of vitamin D, has anti-inflammatory effects and can prevent experimental
      Parkinson's disease (PD). 1,25(OH)2D3 exerts most of its actions only after it
      binds to its specific nuclear receptors. Eighty-five Korean patients with PD and
      231 unrelated healthy individuals were evaluated to determine if vitamin D
      receptor gene (VDRG) BsmI polymorphisms were markers for the susceptibility to PD
      in Korean patients. Each polymorphism was detected using polymerase chain
      reaction (PCR)-based restriction analysis. In addition, the relationship between
      the BsmI polymorphisms and the clinical manifestations of PD was evaluated.
      Overexpression of the b allele (91.2 vs. 85.7%; p=0.069) and homozygote bb (84.7
      vs. 72.7%; p=0.043) was found in the PD patients compared with the controls.
      These results show for the first time an association between PD and a VDRG
      polymorphism, which might be involved in the pathogenesis of PD, or in the
      linkage disequilibrium of the VDRG to another pathogenic gene locus.

PMID- 15953877
TI  - A novel mutation (A148V) in the glucose 6-phosphate translocase (SLC37A4) gene in
      a Korean patient with glycogen storage disease type 1b.
AB  - We report a Korean patient with glycogen storage disease type 1b (GSD-1b) whose
      diagnosis was confirmed by liver biopsy and laboratory results. The patient
      presented with delay of puberty and short stature on admission and had typical
      clinical symptoms of GSD as well as chronic neutropenia and inflammatory bowel
      disease. Mutation analysis of the glucose 6-phosphate translocase 6-phosphate
      translocase (SLC37A4) gene revealed that the patient was a compound heterozygote
      of two different mutations including a deletion mutation (c.1042_1043delCT;
      L348fs) and a missense mutation (A148V). The L348fs mutation was inherited from
      the patient's father and has been reported in an Italian family with GSD-1b,
      while the A148V mutation was transmitted from the patient's mother and was a
      novel mutation. To the best of our knowledge, this is the first report of
      genetically confirmed case of GSD-1b in Korean.

PMID- 15953878
TI  - A case of hypothyroidism and type 2 diabetes associated with type V
      hyperlipoproteinemia and eruptive xanthomas.
AB  - Primary hypothyroidism and type 2 diabetes are both typically associated with the
      increased level of triglycerides. To date, there have been only a few case
      reports of type 2 diabetes patients with both type V hyperlipoproteinemia and
      eruptive xanthomas, but there have been no reports of hypothyroidism patients
      associated with eruptive xanthomas. We report here on a case of a 48-yr old
      female patient who was diagnosed with type 2 diabetes and primary hypothyroidism
      associated with both type V hyperlipoproteinemia and eruptive xanthomas. We found
      rouleaux formation of RBCs in peripheral blood smear, elevated TSH, and low free
      T4 level, and dyslipidemia (total cholesterol 18.1 mM/L, triglyceride 61.64 mM/L,
      HDL 3.0 mM/L, and LDL 2.54 mM/L). She has taken fenofibrate, levothyroxine, and
      oral hypoglycemic agent for 4 months. After treatment, both TSH level and lipid
      concentration returned to normal range, and her yellowish skin nodules have also
      disappeared.

PMID- 15953879
TI  - A case of reactive plasmacytosis mimicking multiple myeloma in a patient with
      primary Sjogren's syndrome.
AB  - Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease with well
      documented association of lymphoid malignancies during the progress of the
      disease. Although several types of malignancy and pseudomalignancy have been
      reported in pSS, low-grade non-Hodgkin's lymphomas are the most frequently
      observed. Reactive plasmacytosis mimicking myeloma is a very rare condition in
      association with pSS. We describe a 72-yr-old woman with pSS who presented with
      hypergammaglobulinemia, and extensive bone marrow and lymph node plasmacytosis,
      which mimicked multiple myeloma. In this patient, there was an abnormal
      differentiation of memory B cells to plasma cells in the peripheral blood
      suggesting underlying pathogenetic mechanism for this condition.

PMID- 15953880
TI  - Giant cystic chondroid hamartoma.
AB  - We report a case of huge pulmonary chondroid hamartoma with multilocular cysts in
      a 38-yr-old male patient. The lobectomy specimen of the left lower lobe showed a
      large multilocular cystic mass, 11.5 x 10 cm in size. The mass had thin-walled,
      variable-sized cysts and areas of solid cartilaginous small nodules in the
      interstitium, which occupied the superior segment and the upper portion of the
      basal segment. There was no connection with bronchus or vessel. Microscopically,
      the cysts and cleft-like spaces were lined by ciliated columnar epithelium and
      the solid components were composed of cartilage, myxohyalinized connective
      tissue, and adipose tissue. Also seen were foci of calcification within the
      sclerotic stroma.

PMID- 15953881
TI  - Concurrent male gynecomastia and testicular hydrocele after imatinib mesylate
      treatment of a gastrointestinal stromal tumor.
AB  - We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia
      and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male
      patient presented for management of hepatic masses. Two years earlier, he had
      undergone a small bowel resection to remove an intraabdominal mass later shown to
      be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan
      revealed multiple hepatic masses, which were compatible with metastatic GIST, and
      he was prescribed imatinib 400 mg/day. During treatment, he experienced painful
      enlargement of the left breast and scrotal swelling. Three months after cessation
      of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he
      experienced painful enlargement of the right breast and scrotal swelling. He was
      diagnosed with male gynecomastia caused by decreased testosterone and
      noncommunicative testicular hydrocele. He was given androgen support and a
      hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib
      induces gynecomastia and hydrocele is thought to be associated with an inhibition
      of c-KIT and platelet-derive growth factor. This is the first report, to our
      knowledge, describing concurrent male gynecomastia and testicular hydrocele after
      imatinib treatment of a patient with GIST.

PMID- 15953882
TI  - A case of osteoclast-like giant cell tumor of the pancreas with ductal
      adenocarcinoma: histopathological, immunohistochemical, ultrastructural and
      molecular biological studies.
AB  - Osteoclast-like giant cell tumor of the pancreas is a very rare neoplasm, of
      which the histiogenesis remains controversial. A 63-yr-old woman was hospitalized
      for evaluation of epigastric pain. An abdominal computerized tomography revealed
      the presence of a large cystic mass, arising from the tail of pancreas. A distal
      pancreatectomy with splenectomy was performed. Histologically, the tumor was
      composed of mononuclear stromal cells intermingled with osteclast-like giant
      cells. In addition, there was a small area of moderately to well differentiated
      ductal adenocarcinoma. The final pathologic diagnosis was osteoclast-like giant
      cell tumor of the pancreas with ductal adenocarcinoma. Here, we describe the
      histopathological, immunohistochemical, ultrastructural and molecular biological
      findings of this tumor with review of the literature pertaining to this
      condition.

PMID- 15953883
TI  - Normal gallbladder visualization during post-ablative iodine-131 scan of thyroid
      cancer.
AB  - Whole body iodine-131 scan is a well-established imaging method for the detection
      of metastatic or residual tumor sites in patients with well-differentiated
      thyroid cancer. Many false-positive iodine-131 scan findings mimicking metastatic
      thyroid cancer have long been reported. The authors describe a false positive
      uptake in normal gallbladder on post-ablative iodine-131 scan in a patient with
      papillary thyroid cancer. This finding should be considered to be another
      possible false-positive finding on iodine-131 whole body scan.

PMID- 15953884
TI  - A case of femoral compressive neuropathy in AL amyloidosis.
AB  - We describe a case of a 54-yr-old AL amyloidosis patient who developed femoral
      compressive neuropathy due to iliopsoas pseudohypertrophy. The patient, who
      presented with end stage renal disease, was referred to our clinic because of
      lower extremity weakness and polyarthritis. Finally, he was diagnosed as having
      kappa-AL amyloidosis, complicated by femoral compressive neuropathy, hypertrophic
      amyloid myopathy, amyloid arthropathy, carpal tunnel syndrome, and end stage
      renal disease. Femoral compressive neuropathy has never been reported in
      association with amyloid induced iliopsoas hypertrophic myopathy. This report
      expands the clinical spectrum of AL amyloidosis.

PMID- 15953885
TI  - More on Botox treatment.

PMID- 15953887
TI  - What do we want to know?

PMID- 15953886
TI  - Botox for excessive gingival display.

PMID- 15953888
TI  - Long-term follow-up of severely resorbed maxillary incisors after resolution of
      an etiologically associated impacted canine.
AB  - BACKGROUND: Resorption of maxillary incisor roots because of an impacted canine
      is a well-recognized phenomenon that occurs in a surprisingly high proportion of
      patients with impacted canines. In this retrospective study, we studied a sample
      of patients in whom the resorption was particularly severe. METHODS: The sample
      consisted of 11 patients (age, 11.8 +/- 1.2 years) with 20 severely resorbed
      maxillary incisors. The amount of resorption was measured at the outset (T1),
      when the impacted canine was distanced from the incisor root area (T2), at the
      completion of the orthodontic treatment (T3), and at a follow-up appointment at
      least 1 year posttreatment (T4). RESULTS: A 17.2% increase in the crown/root
      ratio occurred due to aggressive continued resorption between T1 and T2. The
      resorption rate reduced to an almost insignificant level, despite continued and
      often appreciable orthodontic movement of the resorbed teeth from T2 to T3.
      CONCLUSIONS: Patients with impacted canines should be screened for resorption and
      the impacted tooth treated as soon as possible. The resorption process can be
      halted and the affected tooth moved orthodontically without further risk of
      resorption. In the long term, with early treatment, even severely resorbed teeth
      do not suffer from increased mobility or discoloration and might not require
      splinting.

PMID- 15953889
TI  - Fractal analysis of the PDL-bone interface and implications for orthodontic tooth
      movement.
AB  - BACKGROUND: The periodontal ligament (PDL) is a soft tissue interposed between
      the tooth and the alveolar bone. It is responsible for transmission of forces in
      vivo; this promotes bone remodeling. The purpose our study was to use fractal
      analysis to quantify the complex morphology of the PDL-bone interface. METHODS:
      We used Scion Image (Scion Corp, Frederick, Md) and Benoit fractal analysis (Tru
      Soft International, St. Petersburg, Fla) programs to calculate the fractal
      dimension of the PDL-bone interface in rats via the box-counting method. Rats in
      the experimental groups received an initial force of 0.1N or 0.5N with customized
      springs for 6 hours. RESULTS: Our studies showed an increase in normal fractal
      dimension at the root apices of the rats' maxillary molars. We also found
      evidence that the fractal dimension varies along the entire root length from the
      apex to the cementoenamel junction. CONCLUSIONS: Mechanical loading might lead to
      an increase in fractal dimension at the PDL-bone interface apart from mechanisms
      of bone cell directed remodeling. These changes in fractal dimension are
      proportional to loading and could provide a new parameter for force determination
      in orthodontic tooth movement.

PMID- 15953890
TI  - Effect of fluoride prophylactic agents on the mechanical properties of nickel
      titanium-based orthodontic wires.
AB  - BACKGROUND: Titanium-based alloys have high corrosion resistance because they
      form a thin, stable oxide layer. Nevertheless, fluoride prophylactic agents can
      cause corrosion and associated discoloration of titanium-based orthodontic wires.
      The purpose of this investigation was to study the effects of fluoride
      prophylactic agents on the mechanical properties of nickel-titanium (Ni-Ti) and
      copper-nickel-titanium (Cu-Ni-Ti) orthodontic archwires. METHODS: Preformed
      rectangular Ni-Ti and Cu-Ni-Ti wires were immersed in either an acidulated
      fluoride agent, a neutral fluoride agent, or distilled water (control) for 1.5
      hours at 37 degrees C. After immersion, the loading and unloading elastic modulus
      and yield strength of the wires were measured with a 3-point bend test in a water
      bath at 37 degrees C, in accordance with the criteria in the current American
      National Standard/American Dental Association Specification No. 32 for
      Orthodontic Wires (2000). Scanning electron microscopy was also used to
      characterize the effects of the fluoride treatment on the wire topography.
      RESULTS: Unloading mechanical properties of Ni-Ti orthodontic wires were
      significantly decreased after exposure to both fluoride agents (1-way analysis of
      variance [ANOVA] and Dunnett's post hoc, alpha =.05); however, Cu-Ni-Ti wire
      mechanical properties were not significantly affected by either fluoride agent (1
      way ANOVA, alpha =.05). Corrosive changes in surface topography were observed for
      both wires, with Cu-Ni-Ti appearing to be more severely affected. CONCLUSIONS:
      The results suggest that using topical fluoride agents with Ni-Ti wire could
      decrease the functional unloading mechanical properties of the wire and
      contribute to prolonged orthodontic treatment.

PMID- 15953891
TI  - Resistance to sliding with 3 types of elastomeric modules.
AB  - INTRODUCTION: Super Slick (TP Orthodontics, LaPorte, Ind), a polymeric-coated
      ligature, has recently been introduced to the orthodontic market. The
      manufacturer claims it will significantly reduce friction. The purposes of this
      study were to determine whether Super Slick modules show lower friction than
      round and rectangular modules and to put the frictional forces into perspective
      with a self-ligating bracket. METHODS: Maxillary premolar, stainless steel, self
      ligating, and monocrystalline brackets with .022-in slots were used with straight
      lengths of .018-in and .019 x .025-in stainless steel wires. Buccal segment
      models were set up with 1 molar band and 2 premolar brackets for each test group:
      self-ligating brackets with the slide closed, self-ligating brackets with the
      slide open, and monocrystalline brackets. The latter 2 groups were tested with
      all 3 types of elastomeric module. Each setup was tested both under dry
      conditions and after soaking in a water bath for 1 hour. RESULTS: The self
      ligating brackets demonstrated virtually zero friction with each combination of
      wire and environmental condition. When the different bracket and elastomeric
      module combinations were compared, significant differences were observed. In all
      but 2 combinations, round modules provided the least resistance to sliding and
      rectangular modules the greatest, with Super Slick modules in between the 2. The
      self-ligating bracket provided the least resistance to sliding of all the
      bracket/ligation combinations and almost entirely eliminated friction under the
      conditions of this experiment. CONCLUSIONS: Super Slick modules demonstrated
      greater resistance to sliding than conventional round modules, but not
      rectangular. Self-ligating brackets provided the least resistance to sliding of
      all bracket/ligation combinations and were the only method that almost entirely
      eliminated friction. The .018-in and .019 x .025-in wires exhibited similar
      friction in the dry state, but, when wet, the .018-in wire produced less
      friction. Ceramic brackets demonstrated greater resistance to sliding than
      stainless steel brackets. Lubrication reduced the friction with .018-in wires and
      increased it for .019 x .025-in wires.

PMID- 15953892
TI  - Facial attractiveness: a longitudinal study.
AB  - BACKGROUND: The aim of the study was to investigate various factors that might
      affect facial attractiveness from ages 11 to 31 years. METHODS: Sixty subjects
      were selected from a sample participating in the longitudinal Cardiff Survey.
      Three-quarter-view facial photographs were taken of the subjects smiling and not
      smiling. Photos were taken in 1981, when the subjects were aged 11 years, and in
      2001, when they were aged 31. Twelve judges used a 9-point Likert scale to
      evaluate overall facial attractiveness and the attractiveness of various facial
      features. The judges were also asked to estimate the adults' ages. Univariate and
      multivariate statistical tests and the generalizability theory were used. RESULTS
      AND CONCLUSIONS: Overall facial attractiveness does not depend on any single
      feature; smiling and youthful facial appearance make women look more attractive;
      facial attractiveness tends to decrease over time from ages 11 to 31; people tend
      to retain their relative levels of attractiveness throughout their life spans;
      orthodontic treatment improves dental appearance, but it does not necessarily
      make a person more attractive in the long term. Nevertheless, the positive effect
      of orthodontic treatment could still be observed, especially in men with lower
      levels of facial attractiveness in childhood.

PMID- 15953893
TI  - Ethnic differences in upper lip response to incisor retraction.
AB  - INTRODUCTION: The purpose of this retrospective longitudinal study was to
      investigate the response of the upper lip to incisor retraction and to ascertain
      the effect of ethnicity on this response. METHODS: Pretreatment and posttreatment
      lateral cephalograms of 88 postpubertal female patients (44 black and 44 white;
      mean age, 18.45 years) were evaluated. The groups were matched by age and the
      amount of incisor retraction at incisor superius. RESULTS: Although significant
      pretreatment differences existed between the groups in some cephalometric
      measurements, analysis of the treatment changes demonstrated significant
      differences only in incisor inclination. Hard and soft tissue changes of the
      black group were more downward, whereas changes in the white group were more
      backward. Multivariate regression analysis showed that the horizontal response of
      the upper lip to hard tissue changes at subnasale and superior labial sulcus was
      different in whites than in blacks. At subnasale, stepwise multivariate
      regression analysis showed that ethnicity contributed to the upper lip response
      to incisor retraction and was significantly greater in the white group.
      CONCLUSIONS: The hard and soft tissue treatment changes of the black group were
      more downward, and those of the white group were more backward. Ethnic
      differences exist in the soft tissue response to hard tissue changes in the upper
      lip, and at subnasale and the superior labial sulcus; however, these response
      differences at superior labial sulcus can be explained by the ethnic differences
      in initial lip thickness and incisor inclination; they are not due in and of
      themselves to ethnicity. The change at prosthion was significantly correlated
      with the response of the upper lip at labrale superius to incisor retraction.
      Ethnicity added no increase to the predictability of the response. When incisor
      retraction was performed, the final horizontal upper lip position could be
      accurately and reliably predicted.

PMID- 15953894
TI  - A comparative assessment of the perception of Chinese facial profile esthetics.
AB  - INTRODUCTION: The aim of this study was to compare the perception of male and
      female Chinese facial profile esthetics between dental professionals, dental
      students, and laypersons. MATERIAL: The sample comprised 31 dental professionals
      (20 orthodontists, 11 oral surgeons), 92 dental students, and 152 laypersons in
      an Asian community. The facial profile photographs and lateral cephalometric
      radiographs of a Chinese man and a woman, each with a normal profile, a Class I
      incisor relationship, and a Class I skeletal pattern, were digitized. The digital
      images were modified to obtain 7 facial profiles for each sex. The images were
      constructed by altering cephalometric skeletal and dental hard tissue Chinese
      normative values by 2 standard deviations in the anteroposterior plane only. The
      7 profiles were (1) bimaxillary protrusion, (2) protrusive mandible, (3)
      retrusive mandible, (4) normal profile (Class I incisor with Class I skeletal
      pattern), (5) retrusive maxilla, (6) protrusive maxilla, and (7) bimaxillary
      retrusion. RESULTS: Normal and bimaxillary retrusion Chinese male and female
      profiles were perceived to be highly attractive by all 3 groups. Profiles with a
      protrusive mandible were perceived to be the least attractive. Dental
      professionals, dental students, and laypersons were highly correlated for the
      perception of male (r > 0.67) and female (r > 0.93) profile esthetics. All
      correlation coefficients were found to be significant for the perception of
      female profiles, but, for male profiles, only the correlation coefficient between
      dental students and laypersons was significant. CONCLUSIONS: Chinese male and
      female profiles that were normal or had bimaxillary retrusion were perceived to
      be highly attractive by dental professionals, dental students, and laypersons,
      and profiles with a protrusive mandible were perceived to be the least
      attractive. Dental students and laypersons were more tolerant of a male profile
      with a retrusive mandible than were dental professionals, and all groups were
      more tolerant of bimaxillary protrusion in women than in men. Dental
      professionals, dental students, and laypersons had a similar trend in male and
      female esthetic preferences. The perception of female profiles by all 3 groups
      was highly and significantly correlated. Only the perception of male esthetics by
      dental students and laypersons was not significantly correlated with dental
      professionals.

PMID- 15953895
TI  - Perception of personal dental appearance in Nigerian adolescents.
AB  - BACKGROUND: The purpose of this study was to investigate the relationship among
      Nigerian adolescents' awareness of malocclusion, their satisfaction with personal
      dental appearance, and the severity of their occlusal irregularities. MATERIAL:
      The sample consisted of 577 randomly selected secondary school adolescents-306
      (53%) boys and 271 (47%) girls aged 12 to 17 years (mean age, 14.73 +/- 1.12). A
      pretested questionnaire was used to assess the subjects' awareness of
      malocclusion and satisfaction with personal dental appearance; the actual
      severity of malocclusion was determined by using the dental aesthetic index
      (DAI), performed by an orthodontist in a school environment under natural
      illumination. RESULTS: Statistically significant, negative, weak correlations
      were found between awareness of malocclusion and satisfaction at the various DAI
      scores as follows: < or =25 (r = -0.3774, P < .001), 26 to 30 (r = -0.4305, P <
      .001), 31 to 35 (r = -0.5137, P < .001), and > or =36 (r = -0.5104, P < .001).
      Analysis of variance (ANOVA) did not show a significant value of any of the 3
      factors. Multivariate analysis with age as the covariate did not show a
      significant effect. Also, the association between socioeconomic status and the
      variables was not significant ( P > .05). Generally, no statistically significant
      sex differences were found in relation to the DAI scores, awareness, or
      satisfaction ( P > .05). CONCLUSIONS: Significant, negative, weak correlations
      were found between Nigerian adolescents' awareness of malocclusion and
      satisfaction with personal dental appearance at the various severity levels of
      malocclusion. It would be worthwhile to assess such a relationship with the index
      of orthodontic treatment need in the Nigerian population.

PMID- 15953896
TI  - Comparison of university and private-practice orthodontic treatment outcomes with
      the American Board of Orthodontics objective grading system.
AB  - INTRODUCTION: Treatment outcomes and duration of treatment for patients treated
      in university graduate orthodontic programs and private orthodontic practices
      were assessed and compared with the ABO objective grading system. METHODS: The
      treatment records of 139 randomly selected adolescents who had received
      comprehensive orthodontic treatment were examined. Seventy-seven subjects had
      been treated in 3 postgraduate orthodontic clinics, and 62 had been treated in 3
      private orthodontic practices. Pretreatment, all subjects had Class II Division 1
      malocclusions and ANB angles equal to or greater than 4 degrees . All patients
      were treated with premolar extractions. Posttreatment dental casts were measured
      and scored with the ABO objective grading system. RESULTS: No significant
      differences were found between the groups in the alignment, buccolingual
      inclination, and overjet components. Patients treated in private practice had
      significantly lower scores for marginal ridge height and occlusal relationship.
      Patients treated in the university programs had significantly lower scores for
      occlusal contact and interproximal contact components. CONCLUSIONS: There was no
      significant difference in the overall score, thus no significant difference in
      the overall quality of orthodontic treatment outcome between patients treated in
      university programs and private practices. However, the university group had a
      significantly larger sample variance for the overall score. There was no
      significant difference in the duration of the treatment between patients treated
      in a university setting and in a private practice.

PMID- 15953897
TI  - Dental implants for orthodontic anchorage.
AB  - The purpose of this article is to review and update current concepts involving
      the use of dental implants for orthodontic anchorage. Topics to be discussed
      include indications, implant requirements (eg, materials, size, designs of dental
      implants), surgery and healing time, biomechanics and forces, loading time,
      implant maintenance, posttreatment considerations, and disadvantages.

PMID- 15953898
TI  - Critical aspects in the use of orthodontic palatal implants.
AB  - The concept that osseointegrated implants might provide absolute anchorage has
      led to the introduction of customized orthodontic implants, such as the
      Orthosystem (Institut Straumann, Waldenburg, Switzerland). As this new technique
      evolves, especially with palatal implants, it is evident that many factors
      influence an implant's ease of use and clinical effectiveness. In particular,
      successful placement and subsequent usage depend on control of the profile
      drill's position, inclination, and speed. This article examines the critical
      factors at each stage of the clinical protocol and proposes a standardized
      approach for palatal implants. Particular emphasis is placed on a combined
      process of cephalometric and working model planning. The resultant implant
      prescription is then relayed to the placement stage by using a surgical stent
      with a locating guide plane, as introduced here.

PMID- 15953899
TI  - Skeletal Class III oligodontia patient treated with titanium screw anchorage and
      orthognathic surgery.
AB  - This article reports the successful treatment of a patient, aged 15 years 8
      months, with a Class III malocclusion and oligodontia; a titanium screw was used
      for absolute anchorage during treatment. The patient had a concave profile
      because of mandibular excess and asymmetric spaces in both arches. Titanium
      screws were implanted in the retromolar area during intraoral vertical ramus
      osteotomy combined with LeFort I osteotomy. Absolute anchorage was provided with
      anchorage wires extending from the screws to the left canine and the right
      lateral incisor. After orthodontic space closure, the mandibular molars were
      moved mesially without lingual tipping of the mandibular incisors. A good
      interincisal relationship was achieved. Our results suggest that titanium screws
      and anchorage wires in the retromolar area are useful for the mesial movement of
      mandibular molars.

PMID- 15953900
TI  - Category 2: Skeletal Class II malocclusion with retrognathic mandible and
      hyperdivergent pattern.
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- 15953901
TI  - Orthodontics in 3 millennia. Chapter 3: The professionalization of orthodontics.
AB  - In the 1930s, creative thinkers in orthodontics began to more openly question the
      status quo. Apprenticeships had given way to formal instruction, and proprietary
      schools bowed to graduate university programs, including some taught or headed by
      women. The MD degree was gradually replaced by the MS as the focus of
      orthodontics zoomed out from teeth to the total patient. Angle's dogmatic stance
      against extraction was challenged successfully by his last disciple, Tweed, and
      another of Angle's pupils, Broadbent, developed that century's most important
      diagnostic aid, the cephalometer, which opened the door to Brodie's landmark
      growth studies and Downs's cephalometric analysis. Dentistry's first specialty
      organization, the Society of Orthodontists, was formed in 1900, and the first
      specialty journals appeared.

PMID- 15953902
TI  - Use of a wireless local area network in an orthodontic clinic.
AB  - Radiographic images and other patient records, including medical histories,
      demographics, and health insurance information, can now be stored digitally and
      accessed via patient management programs. However, digital image acquisition and
      diagnosis and treatment planning are independent tasks, and each is time
      consuming, especially when performed at different computer workstations.
      Networking or linking the computers in an office enhances access to imaging and
      treatment planning tools. Access can be further enhanced if the entire network is
      wireless. Thanks to wireless technology, stand-alone, desk-bound personal
      computers have been replaced with mobile, hand-held devices that can communicate
      with each other and the rest of the world via the Internet. As with any emerging
      technology, some issues should be kept in mind when adapting to the wireless
      environment. Foremost is network security. Second is the choice of mobile
      hardware devices that are used by the orthodontist, office staff, and patients.
      This article details the standards and choices in wireless technology that can be
      implemented in an orthodontic clinic and suggests how to select suitable mobile
      hardware for accessing or adding data to a preexisting network. The network
      security protocols discussed comply with HIPAA regulations and boost the
      efficiency of a modern orthodontic clinic.

PMID- 15953903
TI  - Litigation, legislation, and ethics. Carrying the burden of proof.

PMID- 15953904
TI  - An alternative soft tissue analysis following mandibular setback by sagittal
      split ramus osteotomy.
AB  - OBJECTIVE: The objective of this study was to determine alternative ratios of
      soft-to-hard tissue movement after mandibular setback, taking skeletal relapse
      and differing patterns of facial divergence into account. STUDY DESIGN: Thirty
      patients were analyzed cephalometrically over a mean follow-up period of 14
      months. RESULTS: The relationship between skeletal and soft tissue movements in
      the mentolabial folds and at the pogonion was 1:1. Final skeletal relapse was 0.8
      mm at the B-point and 0.5 mm at the pogonion. Hence, the alternative ratios were
      81% and 68%, respectively. The alternative ratio for the mentolabial sulcus was
      considerably lower in the low- than in the high- and medium-angle groups of
      patients. However, there was no statistically significant difference between the
      patient groups with different facial patterns. CONCLUSION: When the smallness of
      the measured relapse and the tracing error are taken into account, the difference
      between the alternative and the conventional ratios was insignificant.

PMID- 15953905
TI  - Efficacy of amoxicillin/clavulanic acid in preventing infectious and inflammatory
      complications following impacted mandibular third molar extraction.
AB  - OBJECTIVE: To find out whether the frequency of postoperative infectious and
      inflammatory complications (IC) in subjects treated with placebo (Pl) is greater
      than those treated with antibiotic (Ab) after extraction of an impacted
      mandibular third molar (M3). Our hypothesis is there are more IC in Pl than in
      Ab, with a maximum ratio difference of 0.067. STUDY DESIGN: A double-blind
      placebo-controlled randomized clinical trial. The sample was derived from the
      population of subjects attending Cruces Hospital for evaluation and extraction of
      1 M3 under local anesthesia. Patients were treated with postoperative placebo or
      amoxicillin/clavulanic acid 500/125 mg 3 times a day during 4 days. The outcome
      variable was infectious and inflammatory complications. Sex, age, smoking, molar
      depth, angulation, need for sectioning, ostectomy, and operation time were
      recorded. Analysis was by intention to treat, risk measures, and logistic
      regression. RESULTS: In 490 subjects (259 Ab and 231 Pl), the frequency of IC was
      1.9% in the Ab and 12.9% in the Pl group (OR 7.6, 95%CI 2.9-19.9; P < .001). The
      number needed to treat was 10 (7-16). Unadjusted relative risk was 0.15 (0.06
      0.38) (P < .001). Absolute reduction risk was 0.11(0.066-0.155)]. Therefore, the
      hypothesis cannot be rejected. Multivariate analysis shows treatment with
      antibiotic (OR = 8.66 (3.17-23.67); P < .001) and age (OR = 1.08 (1.00-1.16); P =
      .029) are the only variables to be included in the logistic regression model.
      CONCLUSION: Amoxicillin/clavulanic acid is efficacious in reducing the incidence
      of IC following third molar extraction but should not be prescribed in all cases.

PMID- 15953906
TI  - Peripheral osteoma of the maxilla: report of an unusual case.
AB  - Peripheral osteomas of the maxilla are relatively rare. A case of a solitary
      peripheral osteoma of the anterior right maxilla in a 16-year-old girl is
      presented. The tumor was asymptomatic and was removed via an intraoral approach
      without any complications. Both hamartomatous and neoplastic factors have been
      advocated concerning the pathogenesis of such lesions, but no definite conclusion
      has been reported. Certain features of the case, such as obstruction of the
      eruption of the permanent canine, displacement of an adjacent tooth,
      intraoperatively noted infiltration of the interdental bone, and clearly abnormal
      histological bone structure might support the neoplastic nature of this lesion.

PMID- 15953907
TI  - Lipomas where you least expect them.
AB  - Although lipomas are relatively common and found in most anatomical sites, we are
      not aware of any previous reports of lipomas arising between the two layers of
      the deep temporal fascia above the zygomatic arch. This is surprising because a
      fat pad is seen and used during surgery in this area to protect the frontal
      branch of the facial nerve. This case highlights the importance of understanding
      the anatomy of this region, because lipomas can potentially arise in any of three
      fat pads laying near the facial nerve in this area.

PMID- 15953911
TI  - The evaluation of jaw function subsequent to bilateral sagittal split osteotomy.
AB  - OBJECTIVE: The objective of the present study was to evaluate the jaw function
      and anatomical changes subsequent to orthodontic treatment combined with
      mandibular advancement or set-back surgery. STUDY DESIGN: The sample consisted of
      67 combined skeletal and dental malocclusion patients, who had received
      orthodontic and surgical treatment previously. Three and 6 months following jaw
      surgery, the following jaw functions were evaluated: the level of occlusal force
      developed, the efficiency of masticatory function, the size in the
      temporomandibular joint (TMJ), the relationship between occlusal force and
      maxillo-mandibular skeletal change, and the range of mandibular movement.
      RESULTS: The results revealed that after surgery the occlusal force, masticatory
      function, TMJ positioning, and mandibular movement distance were all different
      from presurgery values. The surgical set-back group jaw function recovery proved
      to be more rapid than that for the mandibular-advancement group. CONCLUSION:
      Surgical mandibular advancement and set-back by sagittal-split osteotomy
      influence subsequent mandibular function.

PMID- 15953910
TI  - Syphilis: an update.
AB  - Syphilis can be spread during the practice of dentistry by direct contact with
      mucosal lesions of primary and secondary syphilis or blood and saliva from
      infected patients. The dentist also can play an important role in the control of
      syphilis by identification of the signs and symptoms of syphilis, patient
      education, and referral. The incidence of syphilis and the impact of control
      measures are presented with the emphasis on the past 5 years. The signs and
      symptoms of primary, secondary, latent, and late (tertiary) syphilis are
      reviewed. Current medical treatment is presented. The oral manifestations of
      syphilis are discussed as well as the dental management of the infected patient.

PMID- 15953912
TI  - Biodegradable fixation of mandibular fractures in children: stability and early
      results.
AB  - OBJECTIVE: The aim of this study was to assess the safety and efficiency of
      biodegradable self-reinforced (SR-PLDLA) bone plates and screws in open reduction
      and internal fixation of mandible fractures in children. STUDY DESIGN: Thirteen
      patients (5 female, 8 male; mean age 12 years, range 5-16 years) were operated on
      various fractures of the mandible (2 symphyseal, 6 parasymphyseal, 4 body, 3
      angle, 1 ramus, 2 condylar fractures). The mean follow-up time was 26.4 months
      (range 10.9-43.4 months). Intermaxillary fixation was applied in cases with
      concomitant condylar fractures up to 3 weeks. RESULTS: Primary healing of the
      fractured mandible was observed in all patients. Postoperative complications were
      minor and transient. The outcome of the operations was not endangered. Adverse
      tissue reactions to the implants, malocclusion, and growth restrictions did not
      occur during the observation period. CONCLUSIONS: Pediatric patients benefit from
      the advantages of resorbable materials, especially from faster mobilization and
      the avoidance of secondary removal operations. Based on these preliminary
      results, self-reinforced fixation devices are safe and efficient in the treatment
      of pediatric mandible fractures. However, further clinical investigations are
      necessary to evaluate the long-term reliability.

PMID- 15953913
TI  - Analysis of complications following alveolar distraction osteogenesis and implant
      placement in the partially edentulous mandible.
AB  - OBJECTIVE: The purpose of this retrospective study was to evaluate complications
      before, during, and after vertical alveolar distraction osteogenesis and to
      assess the survival rate of dental implants placed in distracted bone. STUDY
      DESIGN: In a consecutive series, 37 patients with 45 alveolar ridge deficiencies
      of the partially edentulous mandible were treated with 14 intraosseous and 31
      subperiosteal distraction devices. Seventy-two dental implants could be placed at
      the time of distractor removal and 21 implants at a second stage. RESULTS:
      Complications associated with the distraction procedure affected 75.7% of
      patients. The majority of complications were of minor nature with the exception
      of fractures of basal bone (n = 3), fracture of transport segment (n = 1),
      breakage of distractor (n = 1), and severe mechanical problems (n = 3). Eleven
      secondary grafting procedures were necessary to allow the placement of dental
      implants. Implant survival was 95.7% (mean postloading follow-up: 35.7 months).
      CONCLUSION: Vertical alveolar distraction osteogenesis is not an uncomplicated
      procedure; however, long-term survival of dental implants inserted into
      distracted areas is satisfactory.

PMID- 15953914
TI  - Comparison of jaw-opening reflexes evoked by Er:YAG laser versus scalpel
      incisions in rats.
AB  - OBJECTIVE: Anecdotal remarks suggest that incisions in oral soft tissue would be
      less painful if performed with laser rather than with scalpel, but such an
      argument remains to be scientifically validated. STUDY DESIGN: Twelve rats
      received graded incisions to lip, gingiva, mucosa, and tongue with either a
      pulsed Er:YAG laser (65 mJ/pulse at 10 Hz) or a stainless steel scalpel. The
      amplitude of the jaw-opening reflex, as measured by the digastric muscle
      electromyogram, was used to quantify the nociceptive response evoked by the
      surgical incisions. RESULTS: Except for lip, mean reflex amplitudes evoked by
      laser were significantly smaller (P < .05) than those evoked by scalpel in all
      other incision sites. CONCLUSION: Er:YAG laser surgery may be less painful and
      therefore require less use of anesthesia and sedation than conventional scalpel
      surgery in oral soft tissue procedures.

PMID- 15953915
TI  - Surgical ciliated cyst of the mandible secondary to simultaneous Le Fort I
      osteotomy and genioplasty: report of case and review of the literature.

PMID- 15953916
TI  - Current controversies in oral lichen planus: report of an international consensus
      meeting. Part 1. Viral infections and etiopathogenesis.
AB  - Despite recent advances in understanding the immunopathogenesis of oral lichen
      planus (LP), the initial triggers of lesion formation and the essential
      pathogenic pathways are unknown. It is therefore not surprising that the clinical
      management of oral LP poses considerable difficulties to the dermatologist and
      the oral physician. A consensus meeting was held in France in March 2003 to
      discuss the most controversial aspects of oral LP. Part 1 of the meeting report
      focuses on (1) the relationship between oral LP and viral infection with special
      emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular
      the immune mechanisms resulting in lymphocyte infiltration and keratinocyte
      apoptosis. Part 2 focuses on patient management and therapeutic approaches and
      includes discussion on malignant transformation of oral LP.

PMID- 15953917
TI  - Oral effects of low-dose methotrexate treatment.
AB  - Methotrexate is used increasingly in low-dose regimes for a variety of
      conditions, particularly rheumatoid arthritis. While certain adverse effects of
      low-dose methotrexate have been described in detail, oral complications have
      received little attention. This article includes a summary of the uses and
      pharmacology of low-dose methotrexate and the mechanisms that lead to general and
      oral toxicity. The literature relevant to potential oral adverse effects is
      discussed and 7 illustrative cases are presented. The oral effects noted range
      from nonhealing ulcers to lymphoma-like lesions. Dental practitioners should be
      aware of the possible oral effects of low-dose methotrexate that have so far been
      largely unrecognized.

PMID- 15953918
TI  - Squamous cell carcinoma of the oral cavity associated with graft versus host
      disease: report of a case and review of the literature.
AB  - Allogenic peripheral stem cell transplantation (HSCT), a procedure that is widely
      used in the treatment of a large number of malignant and nonmalignant
      hematological diseases, is still associated with a wide range of complications,
      one of the most important of which is graft-versus-host disease (GVHD). The
      patients undergoing allogeneic HSCT are at high risk of developing secondary
      neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent,
      but their incidence seems to be higher in the patients who develop GVHD; the most
      frequent solid tumors are squamous cell carcinomas. We here describe the clinical
      course and histopathologic aspects of a squamous cell carcinoma arising on GVHD
      induced oral lesions in a 53-year-old woman with non-Hodgkin's lymphoma
      undergoing allogeneic HSCT. Immediately after the transplantation, the patient
      developed GVHD involving the gastroenteric tract, skin, joints, and oral cavity,
      which was treated with cyclosporin, prednisone, azathioprine, colchicine, and
      photophereses. In addition to the sporadic reports of similar pictures published
      in the literature (16 cases of squamous cell carcinoma owing to oral GVHD in
      patients undergoing allogeneic HSCT), our case underlines the susceptibility of
      HSCT patients with oral GVHD to carcinoma of the oral cavity. All patients
      treated with allogeneic HSCT (particularly those who have developed GVHD) should
      therefore undergo a careful examination of the oral mucosa and be closely
      followed up over the long term with the aim of identifying the onset of secondary
      tumors as early as possible.

PMID- 15953919
TI  - p16 tumor suppressor therapy in salivary adenoid cystic carcinoma cell line
      SACC83.
AB  - OBJECTIVE: This study aimed to determine the growth inhibitory effects of
      transfecting the wild-type p16 gene into human salivary adenoid cystic carcinoma
      (SACC) cells in vitro. METHODS: p16 cDNA was cloned into pDOR-neo plasmid by
      recombination technique, and the human eukaryotic expression vector, pDOR-p16 ,
      was constructed. P16 gene was transfected into SACC83 cells using the liposome
      method, and the expression of the transfected genes was detected by RT-PCR. The
      efficacy of transfection was determined by MTT-based colorimetric formats. The
      DNA metabolic rate of transfected cells was measured by 3 H-TdR incorporation. To
      describe the cell division phase, the cell cycles of the p16 -transfected gene
      cells and untransfected cells were analyzed by flow cytometry. RESULTS: The
      growths in vitro of the p16-transfected cells were inhibited significantly. 3H
      TdR incorporation showed a decreased DNA metabolic rate of p16-transfected cells,
      and flow cytometry suggested a significant increase of the cells in the G1 phase
      and decrease in the S phase. CONCLUSION: The study confirmed the reversal effect
      of wild-type p16 on malignant phenotype of the salivary adenoid cystic carcinoma
      and provides valuable data for further clinical trial of gene therapy with p16.

PMID- 15953920
TI  - Presentation of an epithelioid cell histiocytoma on the ventral tongue.
AB  - The epithelioid cell histiocytoma (ECH) is a polypoidal benign tumor of
      superficial connective tissue that is often diagnosed as a pyogenic granuloma.
      ECHs are speculated to originate from dermal dendritic subunits and are composed
      of 2 primary cell populations, ie, CD34+ primitive fibroblastic dendrocytes and
      factor XIIIa+ histiocytes. Although dendritic subunits are distributed throughout
      most collagenous tissues inclusive of oral mucosa, to date, all reported cases of
      ECH have been cutaneous lesions. ECHs' putative pathogenesis entails activation
      of CD34+ "sentinel" reserve dendrocytes, followed by an influx of histiocytes and
      mast cells. Juxtacrine communication increases release of wound healing factors;
      suggesting a reactive etiologic component. In this current case, the location
      (ventral tongue) and history (recent increase in size) suggest the possibility
      that trauma could have initiated the dendritic subunit "wound healing" cascade.
      Consistent with its benign course, the ECH is managed by local excision, and has
      an excellent prognosis.

PMID- 15953921
TI  - Diagnostic ability of extraoral tuned aperture computed tomography (TACT) for
      impacted third molars.
AB  - OBJECTIVES: The purpose of this study was to evaluate the capabilities of a newly
      developed extraoral TACT system for diagnosing impacted third molars. STUDY
      DESIGN: Three dry human mandibles with impacted third molars were used. Nine base
      images were obtained by the extraoral and intraoral TACT methods. Four board
      certified oral and maxillofacial radiologists evaluated TACT slice images as to
      whether the TACT images could clearly show the periodontal space of the impacted
      third molar, and the location of the tooth relative to the second molar, or to
      the mandibular canal. The criteria were excellent, good, fair, poor, and
      unreadable. RESULTS: Only the visibility of the periodontal space in extraoral
      TACT was significantly inferior to that of intraoral TACT. Almost all of the
      series of TACT images, however, were graded as excellent or good. CONCLUSION: The
      results indicate that extraoral TACT is a useful modality for the clinical
      assessment of impacted third molars.

PMID- 15953922
TI  - Age and trabecular features of alveolar bone associated with osteoporosis.
AB  - OBJECTIVE: To determine the utility of clinical features, combined with optical
      density measurements and morphologic analysis of periapical images, for
      identifying individuals with low lumbar or femoral bone mineral density. STUDY
      DESIGN: Study subjects consisted of 37 females and 29 males. Bone mineral
      densities (BMD) of lumbar spine and proximal femur were measured by dual-energy x
      ray absorptiometry. Clinical variables included subjects' age, height, and
      weight. Optical density and morphologic features were measured from subjects'
      posterior maxilla and mandible. Classification and regression tree analysis was
      used to assess agreement between actual and predicted BMD status. RESULTS: The
      combination of clinical and morphological analysis of trabecular pattern are
      associated with femoral/lumbar BMD. Significant associations were found in the
      maxilla and mandible. The most important clinical variable was age. CONCLUSION:
      This study showed that morphologic analysis of periapical radiographs, combined
      with clinical variables, can assist in identifying individuals with low
      femoral/lumbar BMD.

PMID- 15953923
TI  - Use of a simple intraoral instrument to standardize film alignment and improve
      image reproducibility.
AB  - OBJECTIVE: A lot of instruments and devices were reported in standardized
      realignment of intraoral film. However, these instruments either are too
      cumbersome and time consuming to be used or require extensive fabrication. In
      this study we described a prototype of a instrument for realignment of intraoral
      film and evalated its reproducibility. STUDY DESIGN: A technique that uses this
      instrument was compared with a validated method serving as control. An adult
      human dry skull with full dentition was exposed for measuring the angular errors.
      Two types of angular errors were calculated. RESULTS: of the analysis of the
      alignment error caused by projection of the x-ray beam showed the mean horizontal
      angulation error (+/-SD) was 1.70 +/- 0.75 degrees and the vertical one was 1.32
      +/- 0.44 degrees in the new instrument group, and 1.65 +/- 0.70 degrees and 1.40
      +/- 0.61 degrees, respectively, in the control group. Bite block seating error
      was 2.12 +/- 0.55 degrees in the newly developed instrument and 2.01 +/- 0.49
      degrees in the instrument with registration material. Statistical analysis showed
      no significant difference in the 2 instruments (P > .05). CONCLUSION: The
      prototype of the new instrument reported by the authors can produce almost
      identical radiographs in vitro with only slight angular errors. Clinical use of
      the advanced type of the instrument can be expected to show similar results.

PMID- 15953924
TI  - The sustaining effect of three polymers on the release of chlorhexidine from a
      controlled release drug device for root canal disinfection.
AB  - OBJECTIVES: The aim of this in vitro study was to evaluate the suitability of
      using chitosan, poly (lactide-co-glycolide) (PLGA), and polymethyl methacrylate
      (PMMA) to control the release of chlorhexidine digluconate (CHX) from a prototype
      of controlled release drug device for root canal disinfection. STUDY DESIGN: Four
      different prototypes with different formulations were prepared. Group A (n = 12):
      the device (absorbent paper point) was loaded with CHX as control. Group B (n =
      12): same as group A, but the device was coated with chitosan (Texan MedTech). In
      Groups C and D, the device was treated in the same way as group A and then coated
      3 times with 5% PMMA (Group C, n = 12, Aldrich), or coated 3 times with 3% PLGA
      (Group D, n = 12, Sigma). The devices were randomly allocated to experimental
      groups of 12 each. All the prototypes of controlled release drug device were
      soaked in 3 mL distilled water. The concentrations of CHX were determined using a
      UV spectrophotometer. The surface characteristics of each prototype were observed
      using a scanning electron microscope. RESULTS: The result showed that release
      rate of CHX was the greatest in the noncoated group, followed by the chitosan
      coated group, the PLGA-coated group, and the PMMA-coated group (P < 0.05). Pores
      were observed on the surface of the prototypes that were coated with PLGA and
      PMMA. When the pore size was smaller, the release rate was lower. CONCLUSION:
      These data indicate that polymer coating can control the release rate of CHX from
      the prototypes of controlled release drug device.

PMID- 15953925
TI  - Evaluation of the prognosis and causes of failure in 182 cases of autogenous
      tooth transplantation.
AB  - OBJECTIVES: Autotransplantation is a viable option for treating missing teeth
      when a donor tooth is available. The aim of this study was to evaluate the
      prognosis in addition to the causes of failure in 182 autotransplanted teeth.
      STUDY DESIGN: A total of 182 cases of autotransplantation were analyzed. All the
      transplants were performed according to a computer-aided rapid prototyping
      technique with an average extraoral time of 7.58 minutes. These cases were
      followed for 2 to 60 months after surgery. The prognosis was divided into 4
      groups, complete healing, incomplete healing, uncertain healing, and failure. The
      initial stability, root resorption, and ankylosis were also analyzed. RESULTS:
      Most transplanted teeth showed complete healing between postoperative 2 months
      and 8 months. The transplanted teeth with a good initial stability showed better
      initial healing than those with a poor initial stability. The average extraoral
      time was 7.58 min (range: immediately after extraction up to 25 min). There was
      no relationship (P > .05) between the extraoral time and either root resorption
      (4 cases, 2.4%) or ankylosis (18 cases, 10.7%) within this experimental time
      period. Nine cases (4.5%) failed. CONCLUSION: This study showed a 4.5% failure
      rate during the short to intermediate observation period. Autotransplantation is
      a very useful method for replacing missing teeth, provided that the extraoral
      time and other factors are well controlled.

PMID- 15953926
TI  - Histologic study of furcation perforations treated with MTA or Super EBA in dogs'
      teeth.
AB  - OBJECTIVE: The aim of this study was to investigate the histologic response to
      MTA or Super EBA when used for the repair of furcation perforations in dogs'
      teeth. STUDY DESIGN: Ninety mandibular premolar and molar teeth of 9 mongrel dogs
      were used in this study. The teeth were divided into 3 groups. Seventy-two teeth
      were repaired with either MTA or Super EBA (36 each), and 18 teeth were not
      repaired and used as negative controls. All groups were histologically examined
      at 1 month, 3 months, and 6 months after treatment. Histologic evaluation was
      done with regard to inflammation and type of healing. RESULTS: The Super EBA
      group showed moderate inflammation in 1 month; the inflammation decreased over
      time, but most of specimens showed inflammatory reaction from mild to severe at
      the end of 6 months. The perforation area was filled by connective tissue in
      specimens in which no inflammation was seen. In the MTA group, mild inflammation
      was seen in 1 month, it decreased in 3 months, and no inflammation was detected
      in 6 months. New cementum formation was taken in place in 4 specimens in 1 month,
      in 8 specimens in 3 months, and in all specimens in 6 months. CONCLUSIONS: MTA
      showed less inflammation than Super EBA. MTA specimens showed healing with new
      cementum formation in the perforation area, whereas Super EBA specimens in which
      no inflammation was seen showed connective tissue healing.

PMID- 15953927
TI  - Penetration depth of laser Doppler flowmetry beam in teeth.
AB  - OBJECTIVE: The aim of this study was to determine the penetration depth of laser
      light in teeth for contact and noncontact probe tip. STUDY DESIGN: Fifty-one
      freshly extracted human mature maxillary and mandibular single rooted teeth were
      selected for the study. A laser Doppler flowmeter was used as a laser source. A
      digital camera was used to take pictures (with "night shot" mode in total
      darkness). When probe tip was in contact and when it was 1 mm away from the
      tooth, the depths of the areas illuminated in high and low density were measured.
      RESULTS: In contact probe, root was illuminated to 4.28 +/- 0.14 mm depth with
      high density and 13.27 +/- 0.27 mm depth with low density. In noncontact probe,
      4.36 +/- 0.16 mm with high density and 13.28 +/- 0.30 mm with low density of
      illumination were seen on the root. Between contact and noncontact probe
      situations the difference was not statistically significant in the depth of
      illumination. On the other hand, in both groups the difference between areas
      illuminated in high and low density was statistically significant (P < .05).
      CONCLUSION: Contact or noncontact of the probe on tooth surface did not show any
      significant difference in light penetration. Besides, we think that, for the
      present, it is impossible to eliminate the contamination from periodontal tissues
      completely even if the necessary precautions (periodontal paste etc.) are taken.

PMID- 15953928
TI  - Whither or wither geomicrobiology in the era of 'community metagenomics'.
AB  - Molecular techniques are valuable tools that can improve our understanding of the
      structure of microbial communities. They provide the ability to probe for life in
      all niches of the biosphere, perhaps even supplanting the need to cultivate
      microorganisms or to conduct ecophysiological investigations. However, an
      overemphasis and strict dependence on such large information-driven endeavours as
      environmental metagenomics could overwhelm the field, to the detriment of
      microbial ecology. We now call for more balanced, hypothesis-driven research
      efforts that couple metagenomics with classic approaches.

PMID- 15953929
TI  - Do physiological roles foster persistence of drug/multidrug-efflux transporters?
      A case study.
AB  - Drug and multidrug resistance have greatly compromised the compounds that were
      once the mainstays of antibiotic therapy. This resistance often persists despite
      reductions in the use of antibiotics, indicating that the proteins encoded by
      antibiotic-resistance genes have alternative physiological roles that can foster
      such persistence in the absence of selective pressure by antibiotics. The recent
      observations that Tet(L), a tetracycline-efflux transporter, and MdfA, a
      multidrug-efflux transporter, both confer alkali tolerance offer a striking case
      study in support of this hypothesis.

PMID- 15953930
TI  - Predation on prokaryotes in the water column and its ecological implications.
AB  - The oxic realms of freshwater and marine environments are zones of high
      prokaryotic mortality. Lysis by viruses and predation by ciliated and flagellated
      protists result in the consumption of microbial biomass at approximately the same
      rate as it is produced. Protist predation can favour or suppress particular
      bacterial species, and the successful microbial groups in the water column are
      those that survive this selective grazing pressure. In turn, aquatic bacteria
      have developed various antipredator strategies that range from simply
      'outrunning' protists to the production of highly effective cytotoxins. This
      ancient predator-prey system can be regarded as an evolutionary precursor of many
      other interactions between prokaryotic and eukaryotic organisms.

PMID- 15953931
TI  - Evolution of antifungal-drug resistance: mechanisms and pathogen fitness.
AB  - Like other microorganisms, fungi exist in populations that are adaptable. Under
      the selection imposed by antifungal drugs, drug-sensitive fungal pathogens
      frequently evolve resistance. Although the molecular mechanisms of resistance are
      well-characterized, there are few measurements of the impact of these mechanisms
      on pathogen fitness in different environments. To predict resistance before a new
      drug is prescribed in the clinic, the full spectrum of potential resistance
      mutations and the interactions among combinations of divergent mechanisms can be
      determined in evolution experiments. In the search for new strategies to manage
      drug resistance, measuring the limits of adaptation might reveal methods for
      trapping fungal pathogens in evolutionary dead ends.

PMID- 15953932
TI  - Metabolic footprinting and systems biology: the medium is the message.
AB  - One element of classical systems analysis treats a system as a black or grey box,
      the inner structure and behaviour of which can be analysed and modelled by
      varying an internal or external condition, probing it from outside and studying
      the effect of the variation on the external observables. The result is an
      understanding of the inner make-up and workings of the system. The equivalent of
      this in biology is to observe what a cell or system excretes under controlled
      conditions - the 'metabolic footprint' or exometabolome - as this is readily and
      accurately measurable. Here, we review the principles, experimental approaches
      and scientific outcomes that have been obtained with this useful and convenient
      strategy.

PMID- 15953933
TI  - Prostatic abscess due to Candida tropicalis.
AB  - Fungal urinary tract infection represents a high-risk event in severely ill
      patients. We report a case of a prostatic abscess due to Candida tropicalis with
      no systemic manifestations. In first time, a conservative treatment with
      antifungal treatment and transrectal ultrasound-guided drainage was performed
      without success. Transurethral resection was required for drainage with a
      favourable course.

PMID- 15953934
TI  - Risk factors for disease progression in patients with lower urinary tract
      symptoms/benign prostatic hyperplasia (LUTS/BPH): a systematic analysis of expert
      opinion.
AB  - Disease progression has become an important issue for the management of lower
      urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH). Although several
      risk factors have been identified, no specific patient risk profiles have been
      established that can be useful in the day-to-day management of LUTS/BPH. In this
      study, an international panel of urologists developed a risk classification based
      on the attribution of a risk score to 243 unique patient profiles. From the
      perspective of clinical decision making, it was concluded that postvoid residual,
      symptom severity and maximum flow rate are the most relevant determinants of the
      risk of disease progression.

PMID- 15953935
TI  - Cardiovascular stress responsivity, body mass and abdominal adiposity.
AB  - OBJECTIVE: To assess the relationship between adiposity and cardiovascular stress
      reactivity and recovery in middle-aged men and women, and investigate the
      influence of impaired poststress cardiovascular recovery on changes in body mass
      index (BMI) and waist-hip ratio over 3 y. PARTICIPANTS: In total, 225 healthy men
      and women aged 47-59 y were recruited from the British civil service. METHODS:
      Laboratory mental stress testing was carried out, with blood pressure (BP),
      cardiac output and total peripheral resistance being measured at baseline, during
      moderately challenging tasks, and during recovery 40-45 min poststress. Weight,
      height, waist and hip circumference were assessed at the time of mental stress
      testing and 3 y later. RESULTS: Behavioural tasks elicited increases in BP
      sustained by a combination of cardiac activation and raised peripheral
      resistance. BMI and waist/hip ratio were associated cross-sectionally with
      impaired poststress recovery of systolic pressure, diastolic pressure and cardiac
      index independently of age, gender, socioeconomic status, smoking, alcohol
      consumption and baseline cardiovascular activity. Increases in waist-hip ratio
      over 3 y were predicted both by impaired poststress recovery of systolic pressure
      and cardiac index in men, independently of baseline adiposity and other
      covariates. No associations between subjective stress and BMI or waist-hip ratio
      were observed. CONCLUSIONS: Disturbances of cardiovascular responsivity to
      psychological stress, manifest through impaired poststress recovery, were
      associated cross-sectionally with BMI, and longitudinally with central adiposity
      in men. Stress-related cardiovascular dysregulation may contribute to obesity
      risk.

PMID- 15953936
TI  - Haplotypes in the phospholipid transfer protein gene are associated with obesity
      related phenotypes: the Quebec Family Study.
AB  - BACKGROUND: The phospholipid transfer protein (PLTP) may play a role in body fat
      regulation. OBJECTIVE: To investigate the association between PLTP genetic
      variants and obesity-related phenotypes. METHODS: Two intronic variants, one in
      intron 1 (c.-87G>A) and the other in intron 12 (c.1175+68T>G), were genotyped in
      811 participants of the Quebec Family Study. Nine obesity-related phenotypes were
      investigated, including body mass index (BMI), obesity (BMI> or =30 kg/m(2)), and
      waist circumference, percentage of fat, fat mass and fat-free mass measured by
      hydrostatic weighing as well as total, visceral and subcutaneous abdominal
      adipose tissue areas assessed by computed tomography. Single markers and
      haplotypes were tested for associations in family-based designs using the FBAT
      program. RESULTS: The SNP located in intron 1 showed significant associations
      with obesity, BMI, waist circumference and fat-free mass (P<0.05). The low
      frequency allele (A allele) was associated with higher trait values, suggesting
      that the transmission of this allele is associated with an increased risk of
      being obese. Significant associations were observed between haplotypes and
      obesity, waist circumference, percentage of fat and fat-free mass (P<0.05). The
      transmission of the AT haplotype (frequency=0.180) was positively associated with
      obesity-related phenotypes. After sequencing the promoter and the coding regions
      of the PLTP gene, we were unable to identify a mutation that could replicate
      these results. CONCLUSION: Intronic variants of the PLTP gene are significantly
      associated with obesity-related phenotypes. Considering the number and the
      relevance of candidate genes surrounding the PLTP locus and the absence of
      missense polymorphisms in the coding region, the associations could be mediated
      by a second gene allele in linkage disequilibrium with the marker locus.

PMID- 15953937
TI  - Effects of electroacupuncture in reducing weight and waist circumference in obese
      women: a randomized crossover trial.
AB  - OBJECTIVE: To compare the effects of weight control on simple obese women between
      electroacupuncture and sit-up exercise. DESIGN: Randomized and crossover trial
      conducted from 1 January 2002 to 31 December 2002. The subjects were randomly
      divided into groups A and B. Group A received electroacupuncture treatment first
      while group B received sit-up exercise treatment first. After 6 weeks of
      treatment and 7 days of washout, group A switched to sit-up exercise treatment
      and group B received electroacupuncture treatment for another 6 weeks. PATIENTS:
      In total, 54 simple obese women, with waist circumference (WC)>90 cm and body
      mass index (BMI)>30 kg/m(2), and who had not received any other weight control
      maneuver within the last 3 months. MEASUREMENT: The measurements of body weight
      (BW), BMI and WC were performed at the beginning, 6, 8 and 13 weeks. The data at
      different time periods were compared and expressed as % reductions. RESULTS:
      Electroacupuncture (n=46) showed significant differences in the % reductions in
      BW (P=0.001), BMI (P=0.003) and WC (P=0.005) compared with sit-up exercise. At
      the end of 13 weeks, there were no significant difference between groups A (n=24)
      and B (n=22) in all the measurements. At the end of the study, groups A and B
      showed significant differences in the % reductions in BW (P=0.004; 0.001), BMI
      (P=0.003; 0.021) and WC (P< or =0.001; 0.001) compared with the initial values.
      CONCLUSIONS: Electroacupuncture treatment is more effective than sit-up exercise
      in reducing weight and WC, making it an alternative treatment option for weight
      and WC control on obese women.

PMID- 15953938
TI  - Angiogenic factors are elevated in overweight and obese individuals.
AB  - BACKGROUND: Adipose tissue produces both vascular growth factors and inhibitors.
      Since obesity is associated with expansion of the capillary bed in regional
      adipose depots the balance between these factors may favor angiogenesis.
      OBJECTIVE: To investigate the relationship between body mass index and serum
      concentrations of vascular growth factors in human subjects. METHODS: Vascular
      endothelial growth factor (VEGF), VEGF-C, VEGF-D, soluble VEGF receptor-2
      (sVEGFr2), hepatocyte growth factor (HGF), angiopoietin-2, angiogenin and
      endostatin concentrations were measured in serum collected from 58 lean (24
      males, 34 female, mean BMI, 22.2+/-0.3) and 42 overweight and obese (16 males and
      26 females, mean BMI, 33.5+/-1.2) subjects after an overnight fast. RESULTS:
      Sexual dimorphism was apparent in the serum concentrations of VEGF-C, VEFG-D and
      angiopoietin-2 with significantly higher levels in female compared to male
      subject. VEGF, VEGF-C, VEGF-D, soluble VEGF receptor-2, angiopoietin-2,
      angiogenin and endostatin but not HGF were significantly elevated in overweight
      and obese subjects. Positive correlations between BMI and the serum
      concentrations of VEGF-C, VEGF-D, sVEGF-R2, angiopoietin-2, angiogenin and
      endostatin were observed even after adjustment for gender and age. CONCLUSIONS:
      Increased levels of vascular growth factors as well as the angiogenesis inhibitor
      endostatin are present in overweight and obese subjects and may contribute to
      previously documented increased risk of metastatic disease in obese subjects with
      cancer.

PMID- 15953939
TI  - Canadian Cardiovascular Society/Canadian Heart Rhythm Society position paper on
      implantable cardioverter defibrillator use in Canada.
AB  - The Canadian Heart Rhythm Society in conjunction with the Canadian Cardiovascular
      Society is committed to the promotion of evidence-based practice in Canada. Since
      the last Canadian guidelines on the management of sudden cardiac death were
      published in 2000, several well-conducted clinical trials evaluating the
      implantable cardioverter defibrillator have been completed and published. The
      Canadian Cardiovascular Society Council has granted permission to review and
      update guidelines for the indications for implantable cardioverter
      defibrillators. Furthermore, data are emerging on the potential benefits of
      biventricular pacing therapy (cardiac resynchronization) for heart failure;
      recommendations for the use of this therapy have been included in the present
      paper. Ethical considerations and the economic implications of these
      recommendations are also included. Canada's heart rhythm specialists, represented
      by the Canadian Heart Rhythm Society, have been joined by two heart failure
      specialists, a medical ethicist and an economist, to develop the present position
      paper. Members of the Canadian Heart Rhythm Society participated in the
      discussion of these recommendations in open forum meetings and by electronic
      communication.

PMID- 15953940
TI  - Canadian Cardiovascular Society commentary on implantable cardioverter
      defibrillators in Canada: waiting times and access to care issues.
AB  - The Canadian Cardiovascular Society is the national professional society for
      cardiovascular specialists and researchers in Canada. In the spring of 2004, the
      Canadian Cardiovascular Society Council formed an Access to Care Working Group in
      an effort to use the best science and information to establish reasonable triage
      categories and safe wait times for access to common cardiovascular services and
      procedures. The Working Group has elected to publish a series of commentaries to
      initiate a structured national discussion on this very important issue. Access to
      treatment with implantable cardioverter defibrillators is the subject of the
      present commentary. The prevalence pool of potentially eligible patients is
      discussed, along with access barriers, regional disparities and waiting times. A
      maximum recommended waiting time is proposed and the framework for a solution
      oriented approach is presented.

PMID- 15953941
TI  - Referring patients for consideration of device treatment of sudden cardiac death
      and heart failure: incorporating evidence-based therapies within the Canadian
      health care system.
AB  - The growing use of the implantable cardioverter defibrillator (ICD) in Canada
      reflects the impact that primary and secondary prevention trials have had in
      demonstrating the superiority of the ICD over medical therapy in the prevention
      of sudden cardiac death in high-risk populations. Currently, there are
      significant regional disparities in ICD implantation in Canada. These disparities
      may reflect a lack of regional ICD implant and follow-up programs, and capping of
      funding for ICDs. In addition to increased funding for ICD systems, more
      resources are required to perform device implantations and follow patients over
      the long-term. Potentially eligible patients should be referred to an
      electrophysiologist for consideration of ICD therapy for the prevention of sudden
      cardiac death or to an electrophysiologist/ heart failure specialist for the
      consideration of combination cardiac resynchronization and ICD therapy for the
      management of refractory heart failure.

PMID- 15953942
TI  - Implanted cardioverter defibrillators for the prevention of sudden death.
AB  - Implantable cardioverter defibrillators (ICDs) are effective in preventing sudden
      death from ventricular arrhythmias. Recent clinical trials have demonstrated
      reductions in all-cause mortality in ICD-treated patients, especially those with
      severe left ventricular dysfunction. However, selecting appropriate patients for
      ICD implantation, especially for the primary prophylaxis of all-cause death, is a
      challenge. Patients with recent myocardial infarction (less than 40 days) or
      those that have just undergone coronary artery bypass graft surgery do not
      benefit from ICD implantation. On average, annual death rates are reduced by 1.5%
      to 3.0%, but the risk of death in an individual patient is hard to quantify. Poor
      left ventricular function is the best predictor of both mortality risk and ICD
      benefit. Other risk predictors need to be identified.

PMID- 15953943
TI  - Epidemiology and mechanisms of sudden cardiac death.
AB  - A particular challenge in preventing sudden cardiac death is our limited means of
      identifying individuals, rather than populations, at risk. Genetic and molecular
      risk factors are among the new measures currently being explored. Until effective
      risk recognition and stratification methods are available, general prevention-
      including cardioprotective therapies and the widespread availability of automatic
      external defibrillators--remains important.

PMID- 15953944
TI  - The prevention of sudden cardiac death: the role of the automated external
      defibrillator.
AB  - Sudden death is usually the result of hemodynamically destabilizing ventricular
      tachycardia or ventricular fibrillation. Because the only definitive treatment
      for ventricular tachycardia/ventricular fibrillation is a direct current shock,
      and because that defibrillating shock must be given very quickly to be effective,
      the American Heart Association's "chain of survival" approach to persons with a
      cardiac arrest emphasizes early access to care, early cardiopulmonary
      resuscitation, early cardiac defibrillation and early advanced life support. The
      link in this chain of survival that has been changing most dramatically over the
      past decade is that of early defibrillation. The automated external defibrillator
      enables life-saving defibrillation therapy to be provided to the cardiac arrest
      victim by nontraditional responders, such as the general public. The present
      review evaluates the current role of the automated external defibrillator in the
      ongoing struggle to prevent sudden cardiac death.

PMID- 15953945
TI  - [G691S, L769L and S836S ret proto-oncogene polymorphisms are not associated with
      higher risk to sporadic medullary thyroid carcinoma in Chilean patients].
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) may occur either as sporadic or as
      hereditary. Even though the sporadic form corresponds to the majority of cases,
      the pathogenesis is still unclear. Several polymorphisms of the ret proto
      oncogene, including those located in exon 11, 13, 14 and 15 have been described
      in the general population and some of them seem to be over-represented in
      sporadic MTC patients from European countries, especially G691S, L769L and S836S.
      AIM: To evaluate the allele frequencies of these variants in Chilean patients and
      controls and to determine if these polymorphisms would be associated with the
      development of sporadic MTC from a different genetic population base. SUBJECTS
      AND METHODS: Fifty sporadic MTC patients and 50 normal subjects were tested for
      G691S, L769L, S836S and S904S polymorphisms. The extracted genomic DNA was
      initially analyzed by direct sequencing of PCR products in patients. The presence
      or absence of each polymorphism was also assessed in patients and in control by
      restriction digestion. RESULTS: The allele frequencies showed a similar level of
      the G691S, L769L and S904S variants in both groups. Of interest, we found an
      under-representation of S836S polymorphism in the sporadic MTC group but this
      number was not statistically significant (p=0.141). CONCLUSIONS: We did not find
      an over representation of the G691S, L769 and S836S. These results argue against
      the validity of the association of these polymorphisms as contributing factors in
      the development of sporadic MTC based on a Chilean population and raise questions
      about the importance of these polymorphisms overall.

PMID- 15953946
TI  - [Endovascular treatment of descending aorta trauma].
AB  - BACKGROUND: Mortality of traumatic aortic lesions is over 80%. A group of those
      who survive, develop a chronic pseudo aneurism, usually asymptomatic, that is
      detected during imaging studies. Since conventional surgical treatment of
      traumatic aortic lesions has a great mortality, endovascular treatment has been
      used as an alternative treatment in the last decade. AIM: To report our
      experience with endovascular treatment of traumatic aortic lesions. PATIENTS AND
      METHODS: Report of seven patients aged 22 to 65 years, with traumatic aortic
      lesions. Under general anesthesia an endovascular prosthesis was inserted through
      the femoral artery. RESULTS: No complications were observed in the postoperative
      period, and after a follow up ranging from 4 to 40 months, no endoleaks or other
      complications have been detected. CONCLUSIONS: Endovascular treatment of
      traumatic aortic lesions has good immediate and midterm results.

PMID- 15953947
TI  - [Frequency and characteristics of aspirin resistance in Chilean cardiovascular
      patients].
AB  - BACKGROUND: Studies performed in Anglo-Saxon countries show that 5% of patients
      are resistant to the antiplatelet effects of aspirin. AIM: To assess the
      prevalence of aspirin resistance in a sample of Chilean cardiovascular patients
      and its association with clinical and laboratory characteristics. PATIENTS AND
      METHODS: Ninety nine patients (30 women, 63+/-10 years) treated for stable
      cardiovascular diseases with aspirin 100-325 mg/day were studied. Clinical and
      basic coagulation variables were assessed. Platelet aggregation was studied with
      platelet rich plasma using three different agonists in an optical aggregometer.
      Aspirin resistance was defined as an aggregation 20% with arachidonic acid and an
      aggregation 70% with ADP or collagen. RESULTS: Eleven patients (11.11%, 95% CI=
      4.95-17.27%) complied with both criteria and were classified as aspirin
      resistant. Current smoking was more common in aspirin resistant patients (63.6 vs
      29.6%, p=0.039). CONCLUSIONS: Aspirin resistance was found in a significant
      proportion of cardiovascular patients and was more common among current smokers.

PMID- 15953948
TI  - [In vitro activity of telithromycin against community acquired respiratory
      pathogens].
AB  - BACKGROUND: Telithromycin is a new ketolide antimicrobial, that can be useful for
      the treatment of respiratory infections. AIM: To compare in vitro activity of
      telithromycin against respiratory pathogens, isolated in outpatient clinics.
      MATERIAL AND METHODS: Two hundred eighty strains isolated from patients with
      respiratory infections, were studied. The strains studied were S pneumoniae,
      penicillin sensitive (SPNS:57); intermediate (SPNI:35), resistant (SPNR:25); S
      pyogenes (SP:57); H influenzae (HIN 51); M catarrhalis (MC:25) and S aureus
      meticillin sensitive (SAUS:30). Minimal inhibitory concentration (MIC) by broth
      microdilution was studied for telitrhomycin and levofloxacin in all strains.
      Other antimicrobials studied, but not in all strains were erythromycin,
      clindamycin, trimetoprim sulphamethoxazole, oxacillin, amoxicillin-clavulanic
      acid and cefuroxime. RESULTS: All strains were sensible to telithromycin at a
      concentration -4 microg/ml. MIC 90 and its range for SPNS was 0.03 microg/ml (
      0.004-0.12), for SPNI was 0.03 microg/ml (-0.004-025), for SPNR was 0.06
      microg/ml (-0.004-0.25), for HIN was 2 microg/ml (0.12-4), for SP was 0.5
      microg/ml (-0.004-2), for MC was 0.5 microg/ml (0.06-2) and for SAU was 0.25
      microg/ml (0.06-0.25). CONCLUSIONS: All studied pathogens were sensible to
      telithromycin in vitro. This antimicrobial is an alternative for the treatment of
      community acquired respiratory infections.

PMID- 15953949
TI  - [Risk factors and frequency of positive antibodies for leptospirosis in a sub
      urban population near Santiago].
AB  - BACKGROUND: Leptospirosis is a zoonotic disease and its incidence is known in
      Chile since 2002, when it was incorporated as a disease that must be reported to
      health authorities. A serologic survey for leptospirosis was performed in humans
      and animals from a farm in a semi urban area in Santiago Chile, after the death
      of a farmer due to Weil disease in that place. AIM: To report the prevalence of
      antibodies against leptospirosis and to determine exposure to infection risk
      factors in the humans and domestic animals studied in this survey. MATERIAL AND
      METHODS: Antibodies were detected by IgM immunodot and indirect haemagglutination
      test in 61 humans (43 male, aged 5 to 70 years) and by microscopic agglutination
      test (MAT) in 44 animals. A questionnaire was applied to determine their exposure
      to risk factors for infection with Leptospira. RESULTS: Seventy two percent of
      the studied population were farm workers and 70% had activities that required
      contact with water from canals, 41% cleaned closed places where rodents were
      present. Other risk factors detected were lack of sewage and waste disposal, high
      level of rodent infestation and disposal of faeces into canals used for watering.
      Two humans (3.3%) and six animals (1 bovine and 5 rodents) had positive
      antibodies. Among animals, antibodies against Leptospira serovar pomona and
      icterohaemorragiae were detected. CONCLUSIONS: In Chile, leptospirosis exists not
      only in rural areas but semi urban ones close to Santiago, although the
      prevalence is low. Education is necessary among semi urban population to avoid
      infection.

PMID- 15953951
TI  - [Critical assessment of randomized controlled trials published in biomedical
      Chilean journals].
AB  - BACKGROUND: Well designed clinical trials yield the strongest evidence for the
      effect of health care interventions. AIM: To assess the methodological quality of
      the design and report of randomized clinical trials in a sample, published in
      biomedical Chilean journals between 1980 and 2002. MATERIAL AND METHODS: All
      trials identified by hand search by the Unit of Evaluation of Technologies in
      Health, were assessed for quality of randomization, blinding, analysis of results
      and other characteristics of trial design, along with the application of Jadad's
      Score, that assesses the methodological quality of clinical trials in a scale
      that ranges from 0 to 5. RESULTS: Twenty-eight trials were found and assessed,
      75% (n=21) specified the method used for randomization, 29% (n=8) described a
      correct allocation concealment and 39% (n=11) were double blinded. Withdrawals
      and dropouts were correctly reported in 21% (n=6) of the articles, whereas
      intention to treat analysis was done only in one. Thirteen trials had a Jadad
      score equal or higher than 3 points. CONCLUSIONS: Several design deficiencies
      were found in the trials assessed. It is difficult to know if methodological
      weaknesses are due to incomplete reports or to methodologically poor designs.
      Adopting initiatives like the CONSORT can help improve the quality of randomized
      clinical trials published in Biomedical Chilean journals.

PMID- 15953950
TI  - [Prepatency, parasitemia and histological lesions in mice infected with two
      Trypanosoma cruzi populations isolated in Chile].
AB  - BACKGROUND: The great variability in the clinical presentation of Chagas disease
      may depend in part in the genetic variability of Trypanosoma cruzi populations.
      AIM: To compare prepatent period, parasitemia, mortality and histological lesions
      in mice infected with two populations of Trypanosoma cruzi isolated in Chile.
      MATERIAL AND METHODS: Two Trypanosoma cruzi populations, isolated from Chilean
      Triatomides and genetically characterized by kinetoplast restriction fragment DNA
      profiles, were compared. Two groups of 40 Balb/c mice were studied. Each mouse
      was inoculated with 10(4) trypomastigotes, of the V-121 and sp COMB 2 Trypanosoma
      cruzi populations. The prepatent period, parasitemia, mortality and
      histopathological lesions, at different evolutionary stages of infection were
      registered during 32 days. RESULTS: Prepatency and mortality were similar in both
      groups of mice. However, parasitemia was significantly greater in mice inoculated
      with V-121 than those inoculated with sp COMB 2. Amastigote pseudocysts and
      inflammation were present only in skeletal muscle and myocardium in both groups
      of mice. The intensity of tissue involvement was associated to the level of
      parasitemia, therefore it was greater in mice inoculated with V-121 population.
      CONCLUSIONS: V-121 population of Trypanosoma cruzi caused a greater parasitemia
      than COMB 2, in inoculated mice.

PMID- 15953952
TI  - [Decompressive hemicraniectomy for malignant middle cerebral artery infarction.
      Report of two cases].
AB  - Malignant middle cerebral territory infarction represents 5 to 10% of all brain
      infarctions. Its mortality is 80%, due to brain herniation and it is not reduced
      by medical treatment. Decompressive hemicraniectomy reduces mortality to 12%, and
      the subsequent quality of life of patients is acceptable. We report two male
      patients aged 61 and 54 years, with a malignant middle cerebral territory
      infarction who were treated with decompressive hemicraniectomy. After two years
      of follow up, both patients are self-sufficient and live at home with their
      families.

PMID- 15953953
TI  - [Ischemic brain infarction after an air embolism. Case report].
AB  - Ischemic stroke due to embolic air is uncommon. There are few reports of patients
      with air embolic stroke as a complication of endoscopic procedures. The temporal
      relationship between the stroke and this procedure is the most important clue for
      the diagnosis. CT scan and MRI of the brain are confirmatory tests. The morbidity
      and mortality is high. Patients should be hospitalized in a critical care service
      and treated as soon as possible with oxygen in a pressure camera. We report a 52
      years old woman with an ovarian cancer that, during an upper gastrointestinal
      endoscopy, had a severe alteration of consciousness that did not respond to the
      use of Flumazenil. A CT scan showed multiple areas of air embolism in the
      watershed area between anterior and middle right cerebral arteries. A
      conservative treatment was decided and the patients died 48 hours later.

PMID- 15953954
TI  - [Natural killer cell leukemia. Case report].
AB  - Natural killer leukemia is a rare and highly aggressive neoplasm, is more common
      in young male patients and has a very poor prognosis, with a median survival of
      few weeks. We report a 17 years old male patient who developed, after an acute
      upper respiratory disease, a rapidly multiorganic failure with pancytopenia. Bone
      marrow aspiration and trephine biopsy showed an acute lymphoblastic leukemia. The
      immunophenotype and immunohistochemistry revealed a natural killer acute
      leukemia. The disease progressed rapidly and the patient died shortly after the
      diagnosis.

PMID- 15953955
TI  - [Influence of Mapuche origin and socioeconomic conditions on adult height].
AB  - BACKGROUND: Studies in Chilean adults of low socioeconomic level suggest that
      their low height is likely to be due to their indigenous background. However this
      group also has been marginalized from socioeconomic development. AIM: To
      determine the influence of Mapuche ethnic origin and socioeconomic factors on the
      height of adults. SUBJECTS AND METHODS: In a cross sectional design, the height
      of 1,293 adults (528 males and 765 females) of Mapuche and non Mapuche origin
      were studied in the Araucania Region (Southern Chile) and in the Metropolitan
      Region (Central Chile). Subjects with Mapuche surnames were considered as
      pertaining to this ethnic community and those with Spanish surnames were
      considered as non Mapuche. Linear regression models were done, stratifying by
      sex, considering ethnic origin, to live in counties of different social
      vulnerability, and the level of family poverty. RESULTS: Among males, the mean
      height was 166.6+/-7.3 cm and among females, the figure was 153.6+/-5.9 cm.
      Mapuche subjects were significantly shorter: -3.2 cm (95% Confidence Interval
      (CI) -4.0 to -2.3) among females and -4.8 cm (CI -6.0 to -3.6) among males (non
      adjusted models). This deficit increased to -4.5 and -7.6 cm among females and
      males, respectively when they lived in poverty and in areas with highest social
      vulnerability. These differences decreased significantly if Mapuche subjects
      lived in communities with low social vulnerability and less poverty (-0.59 and 
      1.14 cm among females and males respectively). CONCLUSIONS: The studied
      population had low height, being lower in Mapuche subjects. The differences
      decreased among subjects living in counties of less vulnerability and less family
      poverty.

PMID- 15953956
TI  - [Molecular mechanisms in liver ischemic-reperfusion injury and ischemic
      preconditioning].
AB  - Ischemia-reperfusion (IR) liver injury is associated with temporary clamping of
      hepatoduodenal ligament during liver surgery, hypoperfusion shock and graft
      failure after liver transplantation. Mechanisms of IR liver injury include: i)
      loss of calcium homeostasis, ii) reactive oxygen and nitrogen species generation,
      iii) changes in microcirculation, iv) Kupffer cell activation, and (v) complement
      activation. Pre-exposure of the liver to transient ischemia increases the
      tolerance to IR injury, a phenomenon known as hepatic ischemic preconditioning
      (IP). IP involves: i) recovery of the energy supply and calcium, sodium and pH
      homeostasis, ii) enhancement in the antioxidant potential, and iii) expression of
      multiple stress-response proteins, including acute phase proteins, heat shock
      proteins, and heme oxygenase. These observations and preliminary studies in
      humans give a rationale for the assessment of IP in minimizing or preventing IR
      injury during surgery and non surgical conditions of tissue hypoperfusion.

PMID- 15953957
TI  - [Clinical variants of Alzheimer disease].
AB  - The heterogeneity and variants of Alzheimer disease (AD) are reviewed. There are
      cases with a slow or fast evolution and with early or late onset. Most cases are
      sporadic but there are also hereditary forms. About 50% of patients show
      neuropsychiatric disorders (depression and psychoses). Some cases have a greater
      deficit of right or left hemispheric functions. Among the variants, there are
      forms that start as pure aphasias, predominantly prefrontal cases and posterior
      cortical forms. Occasionally AD may simulate other disorders such as supranuclear
      palsy, corticobasal ganglionar degeneration and Jacob-Creutzfeldt disease.
      Finally, there are mixed forms, in which AD is associated with cerebrovascular
      disease (very commonly) and with other diseases such as dementia with Lewy
      bodies. We conclude that AD is a heterogeneous disorder and, therefore, clinical
      diagnosis may be insufficient. Biological markers and specific imaging studies
      are needed for a correct clinical diagnosis.

PMID- 15953958
TI  - [Professional qualification. Conditions for the quality assurance of medical
      education and the conditions for reciprocal trust. The experience and vision of
      the Association of Medical Schools in Chile (ASOFAMECH)].

PMID- 15953959
TI  - [Homage of the Chilean Academy of Medicine to Pope John Paul II].

PMID- 15953961
TI  - [In Process].

PMID- 15953960
TI  - [Check up and behaviour to be followed on sudden deafness in Emergency Services].

PMID- 15953962
TI  - Developmental toxicity testing from animal towards embryonic stem cells.
AB  - Developmental toxicology is the study of undesirable effects on the development
      of the organism, which may result from exposure before conception, from the
      period of prenatal development, or postnatally during the time of sexual
      maturation. The principal manifestations of developmental toxicity include:
      embryolethality, malformations, growth retardation, and functional impairment. In
      2001, the European Commission published the future chemicals policy entitled
      "White Paper: Strategy for a Future Chemicals Policy". The new regulation
      requires a toxicological evaluation with strong emphasis on reproductive
      toxicity, by using in vitro methods, especially for those chemicals marketed at
      more than 1 ton per year. For this reason, the establishment of in vitro models
      capable of detecting major undesirable manifestations in the fetus, are urgently
      required. The aim of the present review is to explore the capacity of existing in
      vitro systems, based on embryonic stem (ES) cells, to identify embryotoxicity
      with a focus on specific effects such as teratogenicity and growth retardation.
      In addition, we discuss the possibility to adapt the mouse ES cells based tests
      to human ES cells, avoiding inter-species variations in developmental toxicity
      studies and address related ethical issues. Considering the different
      manifestations of developmental toxicity, only a battery of in vitro tests will
      provide the necessary information for regulatory developmental toxicity
      assessment.

PMID- 15953963
TI  - Fourth EU report on the statistics on the number of animals used for scientific
      purposes in 2002 -- trends, problems, conclusions.
AB  - In the beginning of the year 2005, the European Commission published the fourth
      statistical report on the number of laboratory animals used in the EU Member
      States in the year 2002. A total of 10,731,020 experimental animals was reported,
      the majority of which were mice, rats and fish. In comparison to 1999, the year
      of the previous data collection, this is an increase by over 900,000 animals,
      which is mainly attributed to an increased use in fish. As in the previous years,
      France, the United Kingdom and Germany were the Member States that reported the
      highest numbers of laboratory animals. 4.5 million animals were used for the
      development, production and quality control of products for human medicine,
      dentistry and veterinary medicine and 1 million animals in toxicological and
      safety evaluations. 3.7 million animals were used in fundamental studies, and
      therefore are not covered by the scope of Council Directive 86/609/EEC on the
      protection of laboratory animals. This regulatory gap leaving more than a third
      of the laboratory animals used in the European Union without protection by EU
      legislation is unacceptable and should be closed during a revision of the
      Directive. All national authorities submitted some kind of explanatory notes
      alongside their national tables. In the article, an extensive summary and
      discussion of the contents of these notes is presented. Germany, Austria, Finland
      report on providing financial support for the development of alternative methods.
      The numbers put forward in the fourth EU statistical show that such support is
      desperately needed.

PMID- 15953964
TI  - Towards an alternative for the acute fish LC(50) test in chemical assessment: the
      fish embryo toxicity test goes multi-species -- an update.
AB  - After its standardisation at the national level in Germany (DIN 38415-6, 2001,
      2001), the 48 h sewage testing assay with zebrafish (Danio rerio) embryos has
      been submitted for standardisation to ISO. As an alternative to the conventional
      acute (96 h) fish test, a modified fish embryo test will be submitted to the OECD
      for chemical testing in late 2005. For this, a protocol originally designed for
      zebrafish was adapted to fit also the requirements of other OECD species, namely
      medaka (Oryzias latipes) and fathead minnow (Pimephales promelas). Results
      document that the transfer of the protocol is possible with only minor
      modifications. Data obtained from embryo tests with the three species are
      comparable. Statistical analysis of existing zebrafish embryo toxicity data
      resulted in the conclusions (1) that there is a reliable correlation between the
      fish embryo test and the acute fish test, (2) that the confidence belt of the
      regression line was relatively small, but that the prediction range was
      relatively wide. The regression thus seems appropriate to describe the
      relationship between acute fish and embryo LC(50) with good confidence, but is
      less appropriate as a prediction model. Investigations into oxygen requirements
      of zebrafish embryos reveal that they adapt to a broad range of oxygen levels and
      survive at concentrations of 2 mg/l without malformations. Zebrafish embryos can
      thus be exposed in very small toxicant volumes (100 microl), which is of
      particular interest for the testing of metabolites. Dechorionation studies with
      48 h old zebrafish embryos indicate that the barrier function of the chorion
      increases with the lipophilicity of the test compound. Finally, examples are
      given as to how additional endpoints can be incorporated into the fish embryo
      test protocol to extend its scope, e.g. to sediment toxicity assessment or
      genotoxicity and mutagenicity testing.

PMID- 15953965
TI  - Short tandem repeat DNA typing provides an international reference standard for
      authentication of human cell lines.
AB  - Cell lines have wide applications as model systems in the medical and
      pharmaceutical industry. Much drug and chemical testing is now first carried out
      exhaustively on in vitro systems, reducing the need for complicated and invasive
      animal experiments. The basis for any research, development or production program
      involving cell lines is the choice of an authentic cell line. Microsatellites in
      the human genome that harbour short tandem repeat (STR) DNA markers allow
      individualisation of established cell lines at the DNA level. Fluorescence
      polymerase chain reaction amplification of eight highly polymorphic
      microsatellite STR loci plus gender determination was found to be the best tool
      to screen the uniqueness of DNA profiles in a fingerprint database. Our results
      demonstrate that cross-contamination and misidentification remain chronic
      problems in the use of human continuous cell lines. The combination of rapidly
      generated DNA types based on single-locus STR and their authentication or
      individualisation by screening the fingerprint database constitutes a highly
      reliable and robust method for the identification and verification of cell lines.

PMID- 15953966
TI  - [Serological test methods as replacement for infection trials in piglets to test
      the potency of E. coli vaccines for sows (dams)].
AB  - Escherichia coli (E. coli) related diarrhoea poses a major problem in piglet
      production. Vaccination of dams increases the antibody titre in their milk
      against relevant adhesion antigens. Transfer of maternal antibodies via the milk
      can serve to protect the suckling piglets from the disease. However, a marketing
      authorization for veterinary use of these vaccines requires potency determination
      as assayed in infection trials in piglets. Enzyme immunoassays testing the
      antibodies in blood serum and colostrum samples from vaccinated dams against the
      relevant adhesion antigens, F4ab, F4ac, F6 and F41, were developed to replace the
      very distressing infection experiments by in vitro methods. Eight vaccines
      authorized in Germany were included in the trials. Vaccinated sows showed
      significantly higher antibody titres in blood and colostrum than unvaccinated
      control animals. Thus the enzyme immunoassays appear to be suitable to detect
      antibodies against four important adhesion antigens, and can be used to replace
      the distressing infection trials in piglets.

PMID- 15953967
TI  - [EU-Cosmetics: timetables for the replacement of animal experiments].
AB  - According to the 7(th) Amendment of the Cosmetics Directive the European
      Commission had to establish timetables for the phasing out of the various animal
      tests for the safety evaluation of ingredients used in cosmetics. However, the
      published timetables do not reflect the objectives of the 7(th) Amendment but
      contain longer deadlines for the ban on animal experiments of several endpoints.
      The European Commission also had to draw up a Directive for establishing an Annex
      IX that should list validated alternative methods which are not already listed in
      Annex V of the Dangerous Substances Directive. Although various alternative
      methods could have been listed in this Annex IX, the Commission published an
      empty table. From the point of view of the German Animal Welfare Federation
      amendments of the timetables and the Directive establishing Annex IX are urgently
      required. Additionally, the Commission has to provide optimal conditions for the
      replacement of alternative methods.

PMID- 15953975
TI  - A biological approach to characterizing exposure to metalworking fluids and risk
      of prostate cancer (United States).
AB  - OBJECTIVE: Prostate cancer is hormone-related and chemicals that interfere with
      hormones may contribute to carcinogenesis. In a cohort of autoworkers we
      characterized exposure to metalworking fluids (MWF) into age windows with
      homogenous biological risk for prostate cancer, and examined exposure-response
      relationships using semi-parametric modeling. METHODS: Incident cases (n=872)
      were identified via Michigan cancer registry from 1985 through 2000. Controls
      were selected using incidence-density sampling, 5:1 ratio. Using a hormonal-based
      model, exposure was accumulated in three windows: (1) late puberty, (2)
      adulthood, and (3) middle age. We used penalized splines to model risk as a
      smooth function of exposure, and controlled for race and calendar year of
      diagnosis in a Cox model. RESULTS: Risk of prostate cancer linearly increased
      with exposure to straight MWF in the first window, with a relative risk of 2.4
      per 10 mg/m(3)-years. Autoworkers exposed to MWF at a young age also had an
      increased risk associated with MWF exposure incurred later in life. For soluble
      MWF there was a slightly increased risk in the third window. CONCLUSIONS:
      Exposure characterization based on a hormonal model identified heightened risk
      with early age of exposure to straight MWF. Results also support a long latency
      period for exposure related prostate cancer.

PMID- 15953976
TI  - Tobacco use and non-Hodgkin lymphoma: results from a population-based case
      control study in the San Francisco Bay Area, California.
AB  - OBJECTIVE: Investigate the association between tobacco use and non-Hodgkin
      lymphoma (NHL). METHODS: Tobacco-use data were collected during in-person
      interviews in a population-based case-control study of NHL (N=1593 patients,
      N=2515 controls) conducted in the San Francisco Bay Area between 1988 and 1995.
      Odds ratios (ORs) for HIV-negative participants were obtained from adjusted
      unconditional logistic regression models stratified by sex. RESULTS: NHL was not
      associated with overall tobacco use, intensity or duration of cigarette smoking
      in women or men. However, ORs were increased for NHL among men who used any non
      cigarette tobacco alone (OR=1.7), non-cigarette tobacco and cigarettes (OR=1.4),
      multiple types of non-cigarette tobacco alone (OR=2.1) and smokeless tobacco
      alone (OR=4.0). In analyses stratified by sex and age, ORs for NHL associated
      with cigarette smoking in general were above unity among those aged > or =60
      years. ORs for follicular lymphoma were increased in men who used cigarettes and
      other tobacco, cigars alone and smokeless tobacco alone. Diffuse large-cell
      lymphoma in men was associated with use of cigarettes and other tobacco, and
      multiple types of non-cigarette tobacco. CONCLUSION: Our data do not support an
      association between overall tobacco use and all NHL in women or men. Further
      analyses are warranted in larger studies to evaluate non-cigarette tobacco use,
      tobacco-related biologic markers and genetic factors in the development of NHL.

PMID- 15953977
TI  - Two large prospective studies of mortality among men who use snuff or chewing
      tobacco (United States).
AB  - BACKGROUND: Few prospective studies have examined the health risks associated
      with use of snuff and chewing tobacco. METHODS: We studied the association
      between the use of spit tobacco (snuff or chewing tobacco) and mortality among
      men enrolled in Cancer Prevention Study I (CPS-I) in 1959 or Cancer Prevention
      Study II (CPS-II) in 1982. Analyses were based on men who reported exclusive use
      of snuff or chewing tobacco (7745 in CPS-I, 3327 in CPS-II) or no previous use of
      any tobacco product (69,662 in CPS-I, 111,482 in CPS-II) at baseline. Twelve-year
      follow-up of CPS-I, and 18-year follow-up of CPS-II identified 11,871 and 19,588
      deaths, respectively. Cox proportional hazards models were used to control for
      age and other covariates. RESULTS: Men who currently used snuff or chewing
      tobacco at baseline had higher death rates from all causes than men who did not
      in both CPS-I (hazard ratio [HR]=1.17, 95% CI=1.11-1.23) and CPS-II (HR=1.18, 95%
      CI=1.08-1.29). In CPS-I, current use of spit tobacco was statistically
      significantly associated with death from coronary heart disease (CHD), stroke,
      and diseases of the respiratory, digestive, and genitourinary systems, but not
      with death from cancer. In CPS-II, use of these products was significantly
      associated with death from CHD, stroke, all cancers combined, lung cancer, and
      cirrhosis. The associations with cardiovascular and other non-malignant endpoints
      were attenuated, but not eliminated, by controlling for measured covariates.
      Former use of spit tobacco was not associated with any endpoint in CPS-II. No
      clear dose response was observed with either the frequency or duration of usage
      for any endpoint. CONCLUSIONS: These two prospective studies provide limited
      evidence that current use of chewing tobacco or snuff may increase mortality from
      heart disease and stroke.

PMID- 15953978
TI  - The Healthy People 2010 smoking prevalence and tobacco control objectives:
      results from the SimSmoke tobacco control policy simulation model (United
      States).
AB  - OBJECTIVES: Healthy People 2010 (HP2010) set a goal of reducing the adult smoking
      prevalence to 12% by 2010. Smoking prevalence rates do not appear to be declining
      at or near the rate targeted in the HP2010 goals. The purpose of this paper is to
      examine the attainability of HP2010 smoking prevalence objectives through the
      stricter tobacco control policies suggested in HP2010. METHODS: A tested dynamic
      simulation model of smoking trends, known as SimSmoke, is applied. Smoking
      prevalence evolves over time through initiation and cessation, behaviors which
      are in turned influenced by tobacco control policies. We consider the effect of
      changes in taxes/prices, clean air laws, media campaigns, cessation programs and
      youth access policies on projected smoking prevalence over the period 2003-2020,
      focusing on the levels in 2010. RESULTS: The SimSmoke model projects that the
      aging of older cohorts and the impact of policies in years prior to 2004 will
      yield a reduction in smoking rates to 18.4% by 2010, which is substantially above
      the 2010 target of 12%. When policies similar to the HP2010 tobacco control
      policy objectives are implemented, SimSmoke projects that smoking rates could be
      reduced to 16.1%. Further reductions might be realized by increasing the tax rate
      by $1.00. CONCLUSIONS: The SimSmoke model suggests that the HP2010 smoking
      prevalence objective is unlikely to be attained. Although we are unlikely to
      reach the goals by meeting the HP2010 policy objectives, they could get us much
      closer to the goal. Emphasis should be placed on meeting the tax, clean air,
      media/comprehensive campaigns, and cessation treatment objectives.

PMID- 15953979
TI  - A randomized trial to promote pharmacotherapy use and smoking cessation in a
      Medicaid population (United States).
AB  - OBJECTIVE: To evaluate the impact of three different intervention conditions
      designed to increase use of the Medicaid smoking cessation pharmacotherapy
      benefit and promote smoking cessation among Medicaid clients. METHODS: In 2002,
      608 current smokers receiving Medicaid benefits were recruited from the reception
      areas at the Department of Social Services in Erie County, New York, USA.
      Participants were randomized to one of three interventions: Minimal (verbal
      information on the Medicaid pharmacotherapy benefit), Self Help (verbal
      information plus self-help information materials), or Case Management (verbal
      information, self-help information, plus case management assistance to facilitate
      access to the pharmacotherapy benefit). Outcomes included (a) use of a stop
      smoking medication during the three month follow-up period, (b) self-reported 7
      day point prevalence abstinence at three months and (c) bioverified non-smoking
      status at three months (bio-chemically validated by expired Carbon Monoxide (CO)
      < or =8 ppm). RESULTS: 14.6% reported using a stop-smoking medication and staying
      off cigarettes for 24 h, 4.6% self-reported being smoke-free at three months, and
      1.8% were bioverified as smoke-free. There were no differences by intervention
      group for these outcomes. CONCLUSIONS: An intensive intervention designed to
      promote pharmacotherapy use and smoking cessation among Medicaid smokers was no
      more effective than less intensive interventions.

PMID- 15953980
TI  - Choice of exposure scores for categorical regression in meta-analysis: a case
      study of a common problem.
AB  - OBJECTIVE: Reporting categorical relative risk estimates for a series of exposure
      levels versus a common reference category is a widespread practice. In meta
      analysis, categorical regression estimates a dose-response trend from such
      results. This method requires the assignment of a single score to each exposure
      category. We examined how closely meta-analytical categorical regression
      approximates the results of analysis based on the individual-level continuous
      exposure. METHODS: The analysis included five studies on tea intake and outcomes
      related to colorectal cancer. In addition, we derived categorical mean and median
      values from published distributions of tea consumption in similar populations to
      assign scores to the categories of tea intake when possible. We examined whether
      these derived mean and median values well approximate the individual-level
      results. RESULTS: In meta-analytical categorical regression, using the midrange
      scores approximated the individual-level continuous analyses reasonably well, if
      the value assigned to the uppermost, open-ended category was at least as high as
      the lower bound plus the width of the second-highest category. Categorical mean
      values derived from the published distributions of regular tea (in the US) and
      green tea (in Japan) well approximated the slope obtained from individual-level
      analysis. CONCLUSION: Publication of both the categorical and the continuous
      estimates of effect in primary studies, with their standard errors, can enhance
      the quality of meta-analysis, as well as providing intrinsically valuable
      information on dose-response.

PMID- 15953981
TI  - Leisure-time physical activity and lung cancer: a meta-analysis.
AB  - OBJECTIVE: Several studies have evaluated the relationship between physical
      activity and lung cancer. To summarize and review these studies, we conducted a
      meta-analysis of all relevant reports published from 1966 through October 2003.
      METHOD: Adjusted odds ratios (ORs) from the original studies were pooled by the
      inverse of their variance, and all pooled estimates were accompanied by an
      assessment of heterogeneity across investigations. Test for linear trend across
      activity categories (low, moderate, high) were applied. RESULTS: The combined ORs
      were 0.87 (95 confidence interval=0.79-0.95) for moderate leisure-time physical
      activity (LPA) and 0.70 (0.62-0.79) for high activity (p trend = 0.00). This
      inverse association occurred for both sexes, although it was somewhat stronger
      for women. No evidence of publication bias was found. Several studies were able
      to adjust for smoking, but none adjusted for possible confounding from previous
      malignant respiratory disease. Our simulations suggest that this condition is
      unlikely to entirely explain the inverse association. CONCLUSION: The findings of
      this meta-analysis indicate that higher levels of LPA protect against lung
      cancer. The inverse association is possible remains confounded by inadequately
      controlled smoking patterns. However on the whole, confounding seems an unlikely
      explanation for the findings of individual studies on non-smokers.

PMID- 15953982
TI  - CYP1A1 polymorphisms and risk of lung cancer in non-smoking Chinese women:
      influence of environmental tobacco smoke exposure and GSTM1/T1 genetic variation.
AB  - OBJECTIVE: We examined whether polymorphisms of CYP1A1, which plays a role in the
      metabolic activation of polycyclic aromatic hydrocarbons (PAHs), confer an
      increased risk of lung cancer in lifetime non-smoking Chinese women. METHODS: A
      total of 126 incident lung cancer cases, of which 87.7 were pathologically
      confirmed, and 162 age-matched hospital controls were included. CYP1A1 MspI and
      Ile(462)Val polymorphisms were genotyped and tested for association with this
      disease. RESULTS: An elevated risk of lung cancer was observed among individuals
      with the MspI CC (OR=1.7, 95 CI=0.9-3.3) and Ile(462)Val ValVal genotypes
      (OR=2.8, 95 CI=1.1-7.6). After stratifying by environmental tobacco smoke (ETS)
      exposure, the risk of lung cancer associated with both polymorphisms was higher
      among individuals with lower exposure to ETS, compared with those who reported at
      least weekly exposure. Individuals with the MspI CC genotype showed a two-fold
      higher risk of lung cancer if they were also null for either GSTM1 or T1 (OR=2.3,
      95CI=1.0-5.0 and OR=2.7, 95 CI=1.1-6.9, respectively, compared to other genotype
      combinations combined). CONCLUSIONS: CYP1A1 is a susceptibility gene for lung
      cancer among non-smoking Asian women and this association can be influenced by
      ETS exposure and genetic variation at GST genes.

PMID- 15953983
TI  - Previous pregnancy outcome and breast density (United States).
AB  - OBJECTIVE: We evaluated the association of pre-term delivery (PTD), low birth
      weight (LBW), and fetal death with breast density by age at mammogram and years
      since birth. METHODS: Subjects were women aged < or =55 years who had a screening
      mammogram between 1 June 1996 and 1 August 1997 in Seattle, Washington, and whose
      records were linked to their previous state birth (1 January 1968 to 1 August
      1997) or fetal death (1/1/1984-8/1/1997) records. We used unconditional logistic
      regression, adjusting for age at mammogram, body mass index, age at first birth,
      and menopausal status, to calculate the odds of dense (extremely or
      heterogeneously dense by BI-RADS) (n=3593) versus fatty breasts (scattered
      fibroglandular tissue or almost entirely fat) (n=2378) for women with a prior PTD
      (< 34, 34-36 versus > or =37 weeks gestation), LBW (< 2500 versus > or =2500 g),
      or fetal death (stillborn 20 weeks gestation versus live birth). RESULTS: The
      odds for denser breasts increased among women with PTD at <34 weeks gestation who
      were < or =45 years at time of mammogram (odds ratio (OR) and 95 confidence
      interval (CI)=2.8 (1.3-6.1)) and for whom <10 years had elapsed since pregnancy
      (OR=8.8 (1.7-45.8)). We observed similar increases in density among women with
      LBW (OR=3.3 (1.3-8.2)) when <10 years had elapsed. CONCLUSIONS: PTD and LBW may
      have a transitory effect on breast density.

PMID- 15953984
TI  - Socio-economic factors and breast cancer survival--a population-based cohort
      study (Sweden).
AB  - OBJECTIVE: To assess the influence of socio-economic factors on breast cancer
      survival in Sweden, a country with population-based mammography screening and a
      uniform health care system aiming to provide care to all on equal terms. METHODS:
      All women with a first diagnosis of invasive breast cancer in Sweden in 1993 were
      identified in the Swedish Cancer Register. Their sociodemographic characteristics
      were determined by record linkages to the 1970, 1980, 1985 and 1990 Census
      databases, and a nationwide Fertility Register. Information on tumor
      characteristics at diagnosis was obtained from five Swedish Regional Cancer
      Registers. Survival status on 31 December 1998, was assessed through follow-up in
      the Swedish Cause of Death Register. RESULTS: Of totally 4645 eligible women
      diagnosed with breast cancer in 1993, 772 had died from breast cancer through
      1998. After adjustment for tumor characteristics and age, risk of death was 37
      higher among women of low compared to high socio-economic status (HR high vs. low
      0.73; 95 CI: 0.54-0.99). This difference was most pronounced in women less than
      50 years at diagnosis. CONCLUSIONS: These results show that socio-economic
      disparities in breast cancer survival prevail even in this relatively homogenous
      society, offering outreach mammography and standardised treatment regimens in a
      tax-funded health care system.

PMID- 15953985
TI  - Glycemic index, glycemic load, and pancreatic cancer risk (Canada).
AB  - There is some evidence that plasma insulin and postload plasma glucose may be
      associated with risk of pancreatic cancer. Glycemic index and glycemic load are
      measures, which allow the carbohydrate content of individual foods to be
      classified according to their postprandial glycemic effects and hence their
      effects on circulating insulin levels. Therefore, we examined pancreatic cancer
      risk in association with glycemic index (GI), glycemic load (GL), and intake of
      dietary carbohydrate and sugar in a prospective cohort of 49,613 Canadian women
      enrolled in the National Breast Screening Study (NBSS) who completed a self
      administered food frequency questionnaire between 1980 and 1985. Linkages to
      national cancer and mortality databases yielded data on cancer incidence and
      deaths, with follow-up ending between 1998 and 2000. During a mean 16.5 years of
      follow-up, we observed 112 incident pancreatic cancer cases. There was no
      association between overall glycemic index, glycemic load, total carbohydrate and
      total sugar intake and pancreatic cancer risk. In multivariate adjusted models,
      the hazard ratio (HR) for the highest versus lowest quartile levels of overall GI
      and GL were 1.43 (95% confidence interval [CI]=0.56-3.65, P(trend)=0.58) and 0.80
      (95% CI=0.45-1.41, P(trend)=0.41), respectively. Our data suggest that overall
      glycemic index and glycemic load, as well as total sugar and total carbohydrate
      intake, are not associated with pancreatic cancer risk. However, given the
      limited literature regarding the role of diet in the etiology of pancreatic
      cancer, particularly with respect to glycemic index/load, further investigation
      is warranted.

PMID- 15953986
TI  - Occupational risks for uveal melanoma results from a case-control study in nine
      European countries.
AB  - OBJECTIVE: Uveal melanoma is a rare disease with poor prognosis and largely
      unknown etiology. We studied potential occupational risk factors. METHODS: A
      population based case-control study was undertaken during 1995-1997 in nine
      European countries using population and colon cancer controls with personal
      interviews. Occupational exposure to sunlight and artificial UV radiation was
      assessed with a job exposure matrix. In total, 320 uveal melanoma cases were
      eligible at pathology review, and 292 cases were interviewed, participation 91%.
      Out of 3357 population controls, 2062 were interviewed, 61%, and out of 1272
      cancer controls 1094 were interviewed, 86%. RESULTS: Using population controls,
      occupational exposure to sunlight was not associated with an increased risk
      (RR=1.24, 95% CI=0.88-1.74), while an excess risk found with use of colon cancer
      controls was attributed to confounding factors. An excess risk in welders was
      restricted to the French part of the data. Cooks, RR=2.40; cleaners, RR 2.15; and
      laundry workers, RR=3.14, were at increased risk of uveal melanoma. CONCLUSION:
      Our study does overall not support an association between occupational sunlight
      exposure and risk of uveal melanoma. The finding of an excess risk of eye
      melanoma in cooks in several European countries is intriguing.

PMID- 15953987
TI  - Factors associated with time to availability for cases reported to population
      based cancer registries.
AB  - OBJECTIVE: Population-based cancer registries provide an excellent source of data
      for cancer surveillance and research. However, delays in reporting and processing
      can affect the accuracy of incidence rates and the availability of cases for
      research. This study was designed to describe factors related to delays in
      availability of cancer cases for epidemiologic analysis. METHODS: We identified
      all cancer cases diagnosed in 2000 and reported to the California Cancer Registry
      by August 2004. We analyzed factors associated with time to availability, defined
      as the time from diagnosis until the time the case was available for research.
      RESULTS: A total of 137,270 cancer cases were reported during the study period.
      The median time to availability for all cases was 382 days. Forty-five percent of
      cases were available within the first 12 months and 96% were available within 24
      months after diagnosis. Cases reported by hospitals had the shortest time to
      availability (373 days) followed by doctors' offices and laboratories. Melanoma
      and prostate cancers had longer times to be available than other types of cancer.
      Time to availability varied by geographic region, but differences by age, gender,
      race and stage at diagnosis were minimal or non-significant. CONCLUSION:
      Strategies are needed to improve timeliness without sacrificing quality and
      completeness.

PMID- 15953988
TI  - The relationship between physical activity and 2-hydroxyestrone, 16alpha
      hydroxyestrone, and the 2/16 ratio in premenopausal women (United States).
AB  - OBJECTIVES: Estrogen is metabolized in the body through two mutually exclusive
      pathways yielding metabolites with different biological activities: the low
      estrogenic 2-hydroxyestrone (2-OHE1) and the highly estrogenic 16alpha
      hydroxyestrone (16alpha-OHE1). The ratio of these metabolites (2/16) may be
      predictive of risk for developing breast cancer. Early evidence has demonstrated
      that exercise may alter estrogen metabolism to favor the weak estrogen, 2-OHE1.
      METHODS: Seventy-seven eumenorrheic females completed physical activity logs for
      two weeks prior to providing a luteal phase urine sample. Concentrations of 2
      OHE1 and 16alpha-OHE1 were measured and the 2/16 ratio computed. Hierarchical
      regression, controlling for age and body mass index (BMI), was used to determine
      relationships between estrogen metabolites and daily physical activity. RESULTS:
      Regression analyses indicated significant positive relationships between physical
      activity and 2-OHE1 and the 2/16 ratio (p < 0.05) that appears to be independent
      of BMI. 16alpha-OHE1 was not significantly related to physical activity.
      CONCLUSION: These results indicate that physical activity may modulate estrogen
      metabolism to favor the weak estrogen, 2-OHE1, thus producing a higher 2/16
      ratio. This alteration in estrogen metabolism may represent one of the mechanisms
      by which increased physical activity reduces breast cancer risk.

PMID- 15953989
TI  - Screening histories of women with CIN 2/3 compared with women diagnosed with
      invasive cervical cancer: a retrospective analysis of the Norwegian Coordinated
      Cervical Cancer Screening Program.
AB  - OBJECTIVE: This study compares the screening history for women with cervical
      intraepithelial neoplasia (CIN) 2/3 or adenocarcinoma in situ (ACIS) with women
      with different stages and subtypes of cervical carcinoma. METHODS: An analysis of
      the Norwegian Coordinated Cervical Screening Program comparing all cases with a
      CIN 2/3/ACIS (N=8586) with all ICC (N=777) in the period 2000-2002. All Pap
      smears since 1992 were used to characterise detection mode and screening history.
      Multinominal regression models estimated the risk associated with detection mode
      and adequate Pap smear history. RESULTS: A wide range of age at diagnosis, from
      16 to 92 years of age was observed regardless of the stage of the disease. Fifty
      five percentage of the women diagnosed with CIN 2/3/ACIS had an adequate
      screening history. Of women diagnosed with SCC, 45.1% in stage I, and 10.5% in
      stage IV had an adequate history. The median age of women with CIN 2/3 (34 years)
      and squamous cervical carcinoma (SCC) stage I (37 years) given an adequate Pap
      smear history was not significantly different. For women with ACC, the proportion
      with adequate screening history was roughly 50% for all stages. After adjustment
      for detection mode and age, the OR for being diagnosed with ICC stage I compared
      to CIN 2/3 was 1.2 (95% CI: 1.0-1.5), while the OR of being diagnosed with ICC
      stage II-IV was 3.4 (95% CI: 2.3-4.8). CONCLUSIONS: Women with CIN 2/3 and ICC
      stage I were similar with respect to screening histories, i.e. detection mode and
      age at diagnosis, while women with ICC stage II-IV seldom had an adequate
      screening history and were diagnosed at a significantly higher age.

PMID- 15953990
TI  - Percutaneous coronary intervention triggers a systemic inflammatory response in
      patients treated for in-stent restenosis -- comparison with stable and unstable
      angina.
AB  - OBJECTIVE AND DESIGN: It is believed that the magnitude of the systemic
      inflammatory response induced by percutaneous coronary intervention (PCI) impacts
      on the long-term outcomes in patients with stable angina (SA) and unstable angina
      (UA). We aimed to determine whether an inflammatory response appears in in-stent
      restenosis (ISR) patients undergoing balloon angioplasty and to assess its
      pattern and magnitude in relation to SA and UA subjects. SUBJECTS: 80 patients
      (59 with SA, 10 with UA, 11 with ISR) were enrolled into the prospective study.
      TREATMENT: SA and UA patients undergoing single vessel coronary balloon
      angioplasty followed by stenting versus ISR subjects in whom only balloon
      angioplasty was performed. METHODS: C-reactive protein (CRP), serum amyloid A
      (SAA), tumor necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) were
      measured in blood samples collected before and 6, 24 h and 1 month after the
      procedure. RESULTS: A comparable pattern of inflammatory response in terms of CRP
      and SAA concentrations in subjects undergoing PCI due to ISR and SA was
      discovered while in unstable patients its magnitude was substantially higher. CRP
      and SAA levels increased significantly in each group with the peak value at 24 h
      and the baseline levels remarkably correlated with the highest markers'
      concentrations. In contrast, preprocedural TNF-alpha concentrations were higher
      in ISR group when compared with SA and UA patients. Additionally, in ISR group a
      twofold increase in their values of borderline significance at 6 h was noted. SA
      and UA subjects were found to have significantly lower TNF-alpha levels at 6 and
      24 h after the intervention though the marker concentrations markedly increased
      with peak values at 1 month. The levels of IL-10 did not differ at any time point
      between the groups. CONCLUSIONS: We suggest that PCI triggers a systemic
      inflammatory response in patients with ISR and considerable differences in its
      pattern when compared with SA and UA patients were demonstrated. Moreover, a high
      preprocedural TNF-alpha level and its increase provoked by PCI in the ISR group
      warrant the need for further investigation of its possible involvement in the
      restenosis process.

PMID- 15953991
TI  - Anti-inflammatory effect of selective estrogen receptor modulators (SERMs) in
      microglial cells.
AB  - OBJECTIVE: Our aim was to study how different SERMs modulate the inflammatory
      responses induced by lipopolysaccharide (LPS) or unmethylated CpG
      oligonucleotides in mouse and rat microglial cells. MATERIALS AND METHODS:
      Inflammatory responses of mouse N9 microglial cells and rat primary hippocampal
      microglia to lipopolysaccharide (LPS) exposure were recorded by the secretion of
      nitric oxide (NO) and cytokine IL-6 in two models where SERM was added either 24
      h before LPS addition or simultaneously or even after the LPS exposure. The
      responses of 17beta-estradiol, tamoxifen, raloxifene and ICI 182.780 were
      compared. Responses were recorded by ELISA, Northern and EMSA assays. RESULTS:
      SERMs but not 17beta-estradiol induced a significant, concentration-dependent
      anti-inflammatory response both in rat primary microglial cells and in mouse N9
      microglial cells. The response was observed both in NO and IL-6 secretion as well
      as in total IL-6 mRNA expression. We have recently observed that histone
      deacetylase (HDAC) inhibitors can potentiate the LPS-induced inflammatory
      response. Raloxifene and tamoxifen inhibited the potentiation of LPS response
      induced by trichostatin A, an HDAC inhibitor, in N9 microglia. A SERM-induced
      anti-inflammatory response was observed in acute models where SERM was added
      simultaneously or even up to 6 h later than LPS exposure. In contrast, the
      pretreatment of N9 microglia with tamoxifen or raloxifene for 30 h before LPS
      exposure did not provide any protection against the LPS response. We also
      observed that the raloxifene-induced protection in N9 microglia was connected to
      a decline of LPS-induced DNA binding activity of AP-1 but not that of NF-kappaB
      transcription factors. CONCLUSIONS: Our results show that tamoxifen, raloxifene
      and ICI 182.780 induce an anti-inflammatory response in acute models of mouse and
      rat microglial cells. It seems that this response is not estrogen receptor
      mediated but, probably, is attributable to some SERM-induced modulation of LPS
      activated pro-inflammatory signalling cascades.

PMID- 15953992
TI  - The C-terminus of murine S100A9 inhibits spreading and phagocytic activity of
      adherent peritoneal cells.
AB  - OBJECTIVE AND DESIGN: In the present study, the effect of a synthetic peptide
      (H(92)-G(102)) identical to the C-terminus of murine S100A9 (mS100A9p) was
      investigated on adherent peritoneal cell function. MATERIALS AND METHODS: For in
      vitro assays, peritoneal cells were obtained from the abdominal cavity of mice
      and incubated, with the different concentrations of mS100A9p, for 1 h, and then
      their spreading and phagocytosis activities were evaluated. For ex-vivo assays,
      cells obtained from animals treated for 1 h with the peptide were submitted to
      the mannose-receptor phagocytosis assay. Shorter homologue peptides to the C
      terminus of mS100A9p were also evaluated on in vitro phagocytosis assays of
      Candida albicans particles. RESULTS: mS100A9p reduced both the spreading index
      and phagocytic activity, in vitro and ex-vivo, independent of the receptor
      evaluated. The homologue peptide corresponding to the H(92)-E(97) region of
      mS100A9p, the zinc-binding motif, was responsible for such an effect. CONCLUSION:
      These results suggest a modulator effect of the C-terminus of S100A9 protein on
      the function of adherent peritoneal cells.

PMID- 15953993
TI  - Effects and mechanisms of total glucosides of paeony on joint damage in rat
      collagen-induced arthritis.
AB  - OBJECTIVE AND DESIGN: To investigate the therapeutic effects and mechanisms of
      total glucosides of paeony (TGP), an effective compound of Chinese traditional
      herbal medicine (CTM), on collagen -induced arthritis (CIA) in rats. MATERIALS:
      CIA was induced in male Sprague-Dawley rats immunized with chicken type II
      collagen in Freund's complete adjuvant. TREATMENT: TGP (25, 50, 100 mg/kg/d) was
      orally administered to rats from day 14 to 28 after immunization. METHODS:
      Arthritis was evaluated by hind paw swelling, polyarthritis index, and
      histological examination. Activities of interleukin-1 (IL-1) and tumor necrosis
      factor alpha (TNFalpha) were determined and the ultrastructure of synoviocytes
      was observed. The proliferation and the production of vascular epidermal growth
      factor (VEGF), basic fibroblast growth factor (bFGF), matrix metalloproteinase 1
      (MMP-1) and MMP-3 in fibroblast-like synoviocytes (FLS) were detected. RESULTS:
      The administration of TGP (25, 50, 100 mg/kg, ig x 14 days) suppressed secondary
      inflammatory reactions and histological changes in CIA model. The ultrastructure
      of synoviocytes from CIA rats was changed, and the level of IL-1 and TNF alpha
      produced by macrophage-like synoviocytes (MLS) from CIA rats was elevated. TGP
      (50, 100 mg/kg, ig x 14 days) inhibited above changes significantly. The MLS
      supernatants of CIA rats induced more cell proliferation and more production of
      VEGF, bFGF, MMP-1 and MMP-3 in FLS of CIA than those supernatants from CIA rats
      treated with TGP (50, 100 mg/kg, ig x 14 days). CONCLUSION: These results
      indicate that TGP exerts a suppressive effect on joint destruction in rat CIA.
      The therapeutic effect of TGP could be associated with its ability to ameliorate
      the secretion and metabolism of synoviocytes and to inhibit the abnormal
      proliferation and VEGF, bFGF, MMP-1 and MMP-3 production by FLS.

PMID- 15953994
TI  - The contribution of mast cells to the late-phase of allergic asthma in rats.
AB  - INTRODUCTION: Mast cells are thought to be the main cause of an immediate
      asthmatic response, but their contribution to the late-phase of asthma is
      unknown. OBJECTIVE: To prove the contribution of preactivated mast cells to the
      late phase of allergic asthma by advanced activation. METHODS: Mast cell function
      in the late-phase of asthma was studied. Rats (wild, +/+ and mast cell deficient,
      Ws/Ws) were challenged with OVA to investigate the relationship between the
      contraction of airways and the population of inflammatory cells in the trachea.
      RESULT: During the entire asthmatic period, the contraction of the airway after
      OVA challenge in +/+ rats was enhanced significantly compared to Ws/Ws rats,
      especially in the late phase. The bronchoalveolar lavage fluid histamine in +/+,
      but not Ws/Ws, rats increased 5.3-fold in 30 min and 3.4-fold in 8 h after
      challenge, significantly. The number of mucosal mast cells in the tracheal
      epithelial layer in +/+ rats increased significantly 2.2-fold over controls at 8
      h after challenge, as demonstrated by in situ hybridization. CONCLUSIONS: Mast
      cells may contribute to the late phase of asthmatic response by continuous mast
      cell activation and the mucosal mast cell number increased in the late phase of
      asthmatic response.

PMID- 15953995
TI  - Heme oxygenase-1 inhibits cigarette smoke-induced increase in the tracheal
      mucosal permeability in guinea pigs in vivo.
AB  - OBJECTIVE: To examine whether heme oxygenase (HO)-1 inhibits cigarette smoke (CS)
      induced increase in the airway mucosal permeability. METHODS: Mucosal
      permeability was quantified by monitoring the rate of appearance in the
      circulation of horseradish peroxidase that had been instilled into the isolated
      tracheal segment in guinea pigs in vivo, after exposure to CS or room air.
      RESULTS: Exposure to 10 puffs of CS did not increase the tracheal mucosal
      permeability but did increase the permeability after pretreatment with zinc
      protoporphyrin, a competitive inhibitor of HO-1. Moreover, pretreatment with
      hemin, a potent inducer of HO-1, inhibited the increase in the permeability of
      the tracheal mucosa induced by 20 puffs of CS exposure. CONCLUSION: It is
      concluded that HO-1 has an important role in suppressing the increase in the
      mucosal permeability induced by CS in guinea pig trachea.

PMID- 15954031
TI  - [Effectiveness of topiramate in migraine prophylaxis, an observational study in a
      consecutive case-serie].
AB  - INTRODUCTION: Open-label studies and three large and controlled trials had
      demostrated the efficacy of topiramate in migraine prophylaxis. OBJECTIVES: The
      objective of this study was to assess the effectiveness and tolerability of
      topiramate in patients not previously treated with any prophylactic drug.
      PATIENTS AND METHODS: Patients selection was made on sequential patients
      attending our outpatient clinic. Patients were adults diagnosed of either
      transformed migraine or migraine with a frequency of more than four migraine
      attacks per month. Topiramate was started at 25 mg and titrated in 4 weeks by
      weekly increments of 25 mg, up to 100 mg/day. Patients were then followed up for
      a 12-week maintenance phase. Efficacy was assessed by change in mean monthly
      migraine attack frequency from baseline. Additional assessments included
      responder rates, mean number of migraine days and global impression by a seven
      point improvement scale. RESULTS: Mean monthly migraine attacks decreased
      significantly from baseline (from 5.2 +/- 2.6 to 2.1 +/- 2.2; p < 0.0001). Sixty
      nine percent of patients were considered responders and mean reduction rate in
      migraine was 55.6 %. Topiramare was overall well tolerated. Twentyfive (28.4 %)
      patients stopped treatment due to adverse events. The most common adverse events
      were paresthesia, weight loss and cognitive effects. Some grade of satisfaction
      was reported by 55 % of patients at the end of the study. CONCLUSION: This
      naturalistic study confirms clinical trial data that 100 mg/day is an effective
      target dose for patients with migraine and presents the possible beneficial
      effect in transformed migraine.

PMID- 15954015
TI  - [Effects of a shared decision making model in psychiatric and neurologic
      practice].
AB  - Involving patients in medical decisions is increasingly being advocated in
      medical fields other than psychiatry and neurology. A model of shared decision
      making might prove to be an ideal way of bridging the gap between patient-centred
      and evidence-based medicine. This report provides a survey of this shared
      decision making model and a discussion of its implications in the fields of
      mental health and neurology.

PMID- 15954032
TI  - [Gait and stability disorders of the elderly. Clinical analysis of a series of
      259 patients older than 70 years].
AB  - INTRODUCTION: Gait and stability disorders of the elderly are frequent and a
      cause of disability, but studies on their clinical features and etiology are
      scarce, including the relationship between both disorders. OBJECTIVES: To
      evaluate an extensive series of patients with gait and stability disorders, its
      clinical variants and posible pathogenic significance. PATIENTS AND METHODS: 259
      patients older than 70 years consulting for chronic gait and stability symptoms
      in an outpatients neurologic clinic were retrospectively reviewed. Several
      clinical and evolution data are analyzed. RESULTS: Mean age was 78.8 years and
      61.8% were women. 52 % were hypertensive. 161 cases had disequilibrium, 91 a
      cautious gait and seven other types of gait abnormality. 11 % had associated
      dementia. 27 % showed subcortical white matter abnormalities on computed
      tomography scan. In 28 cases a specific cause could be established. In follow-up
      33.5 % worsened. Significant differences between cases of disequilibrium and
      cautious gait were increased age, functional disability and turn abnormality in
      the latter. CONCLUSIONS: Disequilibrium and cautious gait of the elderly share
      some clinical features, have few specific causes and vary from mild cases to a
      disabling <<encephalic gait disease>>.

PMID- 15954033
TI  - [Regional correlations between MR imaging perfusion and SPECT in Alzheimer's
      disease].
AB  - INTRODUCTION: Dynamic susceptibility contrast (DSC) is a magnetic resonance (MR)
      technique that provides an estimation of cerebral blood flow (CBF) through the
      obtention of a cerebral blood volume map. As observed with nuclear medicine
      methods, DSC MR studies have demonstrated a temporoparietal hypoperfusion in
      Alzheimer's disease (AD). However, the concurrent validity of DSC and nuclear
      medicine techniques has not been sufficiently investigated. PATIENTS AND METHODS:
      A single-photon emission computed tomography (SPECT) and a DSC MR perfusion study
      were performed consecutively in 14 AD patients. Expert based qualitative
      assessments of CBF were carried out in eight regions of interest (ROI). RESULTS:
      Level of agreement in the studied ROI was highly variable. Presence of large
      blood vessels and patient head movement were possibly the main causes of this
      variability. Nevertheless, when interrater variability was eliminated, intraclass
      correlation coefficients became more uniform, ranging from 0.32 to 0.71.
      CONCLUSIONS: DSC MR imaging was concordant with SPECT at the different cerebral
      lobes of AD patients. The positive findings should be confirmed under better
      technical and methodological conditions.

PMID- 15954034
TI  - [Neurorehabilitation in multiple sclerosis].
AB  - Neurorehabilitation is predominantly an educational, dynamic process based on the
      adaptation of the individual and his environment to the actual neurological
      impairment and focuses on decreasing the impact of disabling neurological
      conditions on the individual in order to achieve optimum quality of life. It has
      been suggested by some that neurorehabilitation is the only approach available to
      us which can improve the limitations in activity and restrictions in social
      participation of people with multiple sclerosis. The neurorehabilitation approach
      is a holistic one and is a fundamental part of neurological care; it should not
      be forgotten by neurologists, especially when dealing with people with chronic
      disabling conditions such as multiple sclerosis. Together with the social model
      of disability, the concept of restorative neurology, as a scientific and
      therapeutic attempt to minimize those impairments directly responsible for the
      disability presented by the person, is recently gaining ground among
      neuroscientists and clinicians. In this review the conceptual basis for
      neurorehabilitation will be presented together with a review of the literature
      concerning the biological aspects of neurorehabilitative therapy
      (neuroplasticity) and the clinical trials evaluating the effectiveness of
      neurorehabilitation in people with multiple sclerosis. Finally, we will consider
      the practical aspects of neurorehabilitation.

PMID- 15954035
TI  - [Macrocephaly the first manifestation of glutaric aciduria type I: the importance
      of early diagnosis].
AB  - INTRODUCTION: The clinical manifestations of glutaric aciduria type I (GA-I)
      usually develop during the first two years of life as acute encephalopathic
      crisis leading to irreversible dystonic. Progressive macrocephaly can be an early
      clinical sign. We report a 9 month old patient with macrocephaly diagnosed of GA
      I in the presyntomatic stage. This early diagnosis and treatment avoided the
      irreversible neurologic damage associated to this disease. CASE REPORT: A 9 month
      old male referred to the pediatrics neurology clinic because of macrocephaly with
      a head circumference of 51 cm (> 97th percentle). At birth this head
      circumference was 37.5 cm (97th percentile) and showed rapid growth during the
      first 4 months of life. In the physical exam there was mild hypotonia and no
      other neurologic alterations with normal psychomotor development. In the work up
      for macrocephaly urinary organic acids were determined showing a glutaric acid:
      78,000 mmol/mol creatinine (normal values: 2-10); 3-hydroxyglutaric acid: 250
      mmol/mol creatinine (normal values: 1-12). Cerebral magnetic resonance (MR)
      performed at 12 months of age showed frontotemporal atrophy with enlargement of
      subarachnoid spaces, a high signal in T2 in the pallidus nucleus and subdural
      hematomas. Genetic analysis showed a mutation S 305 L/Q 352 X in GCDH gene. L
      carnitine and riboflavin supplementation and a diet with restriction of lysine
      and tryptophan was started. Intercurrent illnesses were treated with intravenous
      fluid, glucose and L-carnitine. At 3 years and 6 month of age, he had not shown
      any encephalopathic crisis, he had a normal psychomotor development and no
      dystonia. MR shows mild temporal lobe atrophy without basal ganglia alterations.
      CONCLUSIONS: In GA-I, macrocephaly is an early sign before other neurologic
      alterations. In patients with little or no neurological symptoms, early treatment
      may prevent the acute encephalopathic crisis and neurological deterioration,
      improving the prognosis and may also normalize the basal ganglia
      neuroradiological alterations. Urinary organic acid analysis should be performed
      in the work up of macrocephaly of unknown aetiology.

PMID- 15954036
TI  - [Muscle-eye-brain disease. Presentation of one case with genetic study].
AB  - INTRODUCTION: The objective [corrected] is to present a case of muscle-eye-brain
      (MEB) disease with genetic study. MATERIAL AND METHODS: We studied an affected
      male from the age of 7 months to 21 years. During this time, clinical,
      analytical, neurophysiological (EEG, EMG, visual evoked potential [VEP],
      electroretinogram [ERG]), image (CT, MR), cerebral biopsy and genetic studies
      were performed. RESULTS: Severe visual acuity impairment with optic atrophy from
      the first months of life, abnormal VEP and ERG, CT and MR showing <<cobblestone
      complex>> image of the cerebral cortex and subcortical white matter with
      myelinating changes; the histologic study of the cerebral biopsy sample showed
      hypomyelinating lesions and migration changes. The patient is alive at 21 years
      of age. The genetic study confirmed the presence of two recessive mutations,
      c.1274G>C and c.1895+1_4delGTGA, within the POMGnT1 gene. CONCLUSIONS: The
      patient shows typical clinical, neurophysiological, histological and genetic MEB
      features.

PMID- 15954037
TI  - [Internal carotid artery vasculitis originated by cervicofacial actinomycosis as
      a predisponing factor to stroke].
AB  - Actinomycosis is a chronic, suppurative, fibrotic infection produced by a gram
      positive anaerobic bacteria of the normal mouth flora, the infection having
      tendency to fistulate and to extend without respecting tissue layers. Initial
      diagnosis is usually delayed due to its painless evolution. Three clinical forms
      are known: cervicofacial, abdominal and thoracic. Occasionally, there is vascular
      involvement which is mainly associated with venous thrombotic phenomena with low
      clinical expresion and hematogenous dissemination that can result in a formation
      of abscess or meningitis in the central nervous system. We report the case of a
      28 year old female patient with type I diabetes and microangiopathyc complication
      with a internal carotid artery stenosis adjacent to mandibular angle
      actinomicosis. A few months later and after a miscarriage she suffered from
      ischemic stroke. The anticardiolipin antibody were positive at the time of stroke
      with post-operative period and over the next two years. To our knowledge
      (Medline, 1984-2004), it is the first report of internal carotid vasculitis
      originated by cervicofacial actinomicosis. We discuss the neuroradiological
      aspects of our case.

PMID- 15954038
TI  - [Neuropathy of the second trigeminal nerve branch as debut form of a type 2
      neurofibromatosis with cystic lesion].

PMID- 15954039
TI  - [Sudden bilateral deafness as first manifestation of meningeal carcinomatosis].

PMID- 15954041
TI  - A "Fille du Roy" introduced the T14484C Leber hereditary optic neuropathy
      mutation in French Canadians.
AB  - The predominance of the T14484C mutation in French Canadians with Leber
      hereditary optic neuropathy is due to a founder effect. By use of genealogical
      reconstructions of maternal lineages, a woman married in Quebec City in 1669 is
      identified as the shared female ancestor for 11 of 13 affected individuals, who
      were previously not known to be related. These individuals carry identical
      mitochondrial haplogroups. The current geographic distribution of French Canadian
      cases overlaps with that of the founder's female descendants in 1800. This is the
      first example of genealogical reconstruction to identify the introduction of a
      mitochondrial mutation by a woman in a founder population.

PMID- 15954042
TI  - Evidence-based practice and the limits of rational rehabilitation.
AB  - Both the American Congress of Rehabilitation Medicine and the field of physical
      medicine and rehabilitation have entered an age of evidence-based rehabilitation.
      Despite some concerns over the difficulties in applying the methods of evidence
      based practice to rehabilitation research, there is little question that we will
      continue to move in this direction. This will also require the translation of
      scientific evidence into clinical practice. Rather than representing opposing
      approaches to practice, the integration of the best available scientific evidence
      with clinical experience and judgment represent 2 of the pillars of evidence
      based practice. However, we also need to recognize the subjective nature of
      clinical decision making as a fundamental aspect of human judgments. Finally, we
      need to acknowledge the subjective meanings of illness and disability to the
      patients we serve. Any efforts to build our practice based on the best available
      systematic evidence are unlikely to succeed unless we include patients values and
      beliefs and incorporate this perspective into our rehabilitation research. This
      aspect of evidence-based rehabilitation raises important questions about our
      fundamental roles and how we will choose to practice and define our field in the
      future.

PMID- 15954043
TI  - Pushing the frames of reference in traumatic brain injury rehabilitation.
AB  - Cognitive rehabilitation is an empirically based field driven by multiple sources
      of activities and knowledge bases. Drawing on frames of reference provided by
      rehabilitation, neuropsychology, and rehabilitation psychology, cognitive
      rehabilitation has evolved to a point where studies have been generated to
      qualify for consideration in tables of evidence. At the center of cognitive
      rehabilitation is the effort to teach people to overcome or adapt to limitations.
      While rehabilitation has traditionally been focused on activity, a recent trend
      in the literature is to incorporate the individuals experience into a frame of
      reference for rehabilitation. Emphasizing the experience of the person in the
      situation fits into cognitive rehabilitation and raises the bar for
      rehabilitation not only in viewing rehabilitation as an activity to relieve
      burdens but also in terms of how rehabilitants come to grips with limitations.
      Dealing with limitations is an important indicator of mental health.

PMID- 15954045
TI  - Functional independence domains in patients receiving rehabilitation in skilled
      nursing facilities: evaluation of psychometric properties.
AB  - OBJECTIVE: To provide evidence for the validity of using FIM items to derive 4
      domains of functional independence (mobility, activities of daily living [ADLs],
      sphincter management, executive function) in patients receiving rehabilitation in
      skilled nursing facilities (SNFs). DESIGN: A retrospective analysis of secondary
      data using data from a privately owned administrative dataset. Setting Seventy
      SNFs under contract with SeniorMetrix Inc health plan clients. PARTICIPANTS:
      Patients (N=7536) with a variety of conditions, covered by Medicare+Choice plans,
      and admitted to an SNF in 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Item score distributions, corrected item-total correlations, factor
      correlations, internal consistency, and stage ceiling and floor effects for each
      hypothesized functional independence domain. RESULTS: With the exception of 2
      items, the items within a domain had similar standard deviations and
      distributions of items were not highly skewed. Four factors accounted for 73.4%
      of the variance in functional independence. Corrected item-total correlations
      ranged from .58 to .80 for the ADL domain, from .23 to .71 for the mobility
      domain, and from .78 to .88 for the executive function domain. The correlation
      between bowel and bladder management items was .84. Cronbach alpha coefficients
      ranged from .76 for the mobility domain to .96 for the executive function domain.
      At admission, there were substantial floor effects for the sphincter management
      (34.4%) and mobility domains (43.1%) and ceiling effects for the executive
      function domain (26.7%). CONCLUSIONS: With a few exceptions, the items proposed
      for each functional independence domain met the criteria for supporting the
      validity of the domains.

PMID- 15954044
TI  - The effects of splinting on outcomes for epicondylitis.
AB  - OBJECTIVE: To evaluate the effects of splinting on outcomes for injured workers
      with epicondylitis. DESIGN: Retrospective cohort study using propensity score
      methodology to statistically control for all observed pretreatment differences
      between patients with and without splints. SETTING: Nationwide network of 253
      occupational medicine clinics. PARTICIPANTS: All injured workers (N=4614)
      receiving primary care for lateral or medical epicondylitis (International
      Classification of Diseases, 9th Revision, codes 726.31 or 726.32). INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Physician-prescribed rates of duty
      restrictions and lost time, treatment duration, specialist referrals, and medical
      and physical therapy (PT) visits and charges. RESULTS: Overall, patients with
      splints had higher rates of limited duty ( P <.001), more medical visits and
      charges ( P <.001), higher total charges (medical and PT, P <.001), and longer
      treatment durations ( P <.01) than patients without splints. Evaluating
      differences for patients who did and did not receive PT, significant differences
      remained for rates of limited duty ( P <.05), medical visits ( P <.01), and
      medical charges ( P <.01). CONCLUSIONS: Splinting patients with epicondylitis may
      not optimize outcomes, including rates of limited duty, treatment duration, and
      medical costs.

PMID- 15954046
TI  - Validity of functional independence staging in patients receiving rehabilitation
      in skilled nursing facilities.
AB  - OBJECTIVES: To determine the psychometric performance and clinical applicability
      of the Functional Independence Staging (FIS) system for activities of daily
      living (ADLs), sphincter management, mobility, and executive function in patients
      receiving rehabilitation in the skilled nursing facility (SNF) setting. DESIGN: A
      retrospective analysis of secondary data using data from a privately owned
      administrative dataset. Setting Seventy SNFs under contract with SeniorMetrix Inc
      health plan clients. PARTICIPANTS: Patients (N=7526) covered by Medicare+Choice
      plans and admitted to an SNF in 2002. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: Analysis of construct validity, sensitivity to change, and predictive
      validity. RESULTS: The FIS score in each domain except mobility at admission was
      higher for patients with no concomitant disease than for patients classified as
      moribund ( P <.001). The odds of being discharged to the community were
      consistently greater for patients with higher discharge FIS scores in sphincter
      management (odds ratio [OR] range, 1.32-1.76), mobility (OR range, 1.93-4.66),
      and executive function (OR range, 1.50-4.15). Discharge FIS score was greater
      than admission FIS score for all domains ( P <.001). The odds of being discharged
      to the community were fairly consistently predicted by admission FIS score in
      ADLs (OR range, 1.26-3.73) and executive function (OR range, 1.60-5.05).
      CONCLUSIONS: The FIS system has reasonable psychometric properties that suggest
      it may be applied to the assessment and monitoring of functional status in
      patients admitted for rehabilitation in SNF settings. The system may be useful
      for determining the type of therapy that might be required or to predict the
      likely discharge needs of the patient.

PMID- 15954047
TI  - Association of physical performance measures with bone mineral density in
      postmenopausal women.
AB  - OBJECTIVE: To investigate the association between physical performance measures
      and bone mineral density (BMD) in older women. DESIGN: Cross-sectional analysis.
      SETTING: University research laboratory. PARTICIPANTS: Healthy postmenopausal
      women (N=116; mean age +/- standard deviation, 68.3+/-6.8y) in self-reported good
      health who were not taking medications known to affect bone, including hormone
      replacement therapy. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Anthropometrics and BMD of the hip, spine, whole body, and forearm. Physical
      performance measures included normal and brisk 8-m gait speed, normal step length
      (NSL), brisk step length (BSL), timed 1-leg stance (OLS), timed sit-to-stand
      (STS), and grip strength. RESULTS: NSL, BSL, normal gait speed, brisk gait speed,
      OLS, and grip strength correlated significantly with several skeletal sites ( r
      range, .19-.38; P <.05). In multiple regression models containing body mass
      index, hours of total activity, total calcium intake, and age of menarche, NSL,
      BSL, normal and brisk gait speeds, OLS, and grip strength were all significantly
      associated with BMD of various skeletal sites (adjusted R 2 range, .11-.24; P
      <.05). Analysis of covariance showed that subjects with longer step lengths and
      faster normal and brisk gait speeds had higher BMD at the whole body, hip, and
      spine (brisk speed only). Those with a longer OLS had greater femoral neck BMD,
      and those with a stronger grip strength had greater BMD in the whole body and
      forearm ( P <.05). STS was not related to any skeletal site. CONCLUSIONS: Normal
      and brisk gait speed, NSL, BSL, OLS, and grip strength are all associated with
      BMD at the whole body, hip, spine, and forearm. Physical performance evaluation
      may help with osteoporosis prevention and treatment programs for postmenopausal
      women when bone density scores have not been obtained or are unavailable.

PMID- 15954048
TI  - Measuring medical complexity during inpatient rehabilitation after traumatic
      brain injury.
AB  - OBJECTIVE: To compare the performance of 3 severity of illness (SOI) indices--the
      Comprehensive Severity Index (CSI), All Patient Refined Diagnosis Related Groups
      Severity of Illness, case-mix group (CMG)--and 5 well-known neurologic
      parameters, as measures of medical complexity. DESIGN: Retrospective chart
      review. SETTING: Inpatient rehabilitation center within a level I trauma center.
      PARTICIPANTS: Consecutive traumatic brain injury (TBI) admissions (N=212).
      INTERVENTION: Acute inpatient TBI rehabilitation. CSI and neurologic parameters
      were scored by chart extraction. SOI was based on diagnosis codes by using 3M PC
      Grouper software, version 15. MAIN OUTCOME MEASURES: Adjusted R 2 was used to
      predict rehabilitation charges as a proxy of medical complexity. RESULTS: The
      highest adjusted R 2 values for single variables predicting charges were: CMG
      .349, CSI .293, duration of posttraumatic amnesia .260. Adjusted R 2 values for
      the CMG combined with the CSI, 5 neurologic parameters, and SOI to predict
      charges were .446, .431, and .365, respectively. CONCLUSIONS: The CMG was the
      best single predictor of rehabilitation charges for TBI. Predictive ability was
      better when the CMG was combined with the CSI or a combination of the 5
      neurologic parameters. A severity index based on objective clinical findings
      rather than diagnostic codes may have distinct advantages for rehabilitation
      outcome studies and reimbursement methodology.

PMID- 15954049
TI  - Passive stretching does not enhance outcomes in patients with plantarflexion
      contracture after cast immobilization for ankle fracture: a randomized controlled
      trial.
AB  - OBJECTIVE: To compare the efficacy of short- and long-duration passive stretches
      with a control treatment for the management of plantarflexion contracture after
      cast immobilization for ankle fracture. DESIGN: Assessor-blinded, randomized
      controlled trial. SETTING: Hospital physical therapy outpatient departments.
      PARTICIPANTS: Adults with plantarflexion contracture (N=150) after cast
      immobilization for ankle fracture. All subjects were weight bearing or partial
      weight bearing. INTERVENTIONS: Exercise only, exercise plus short-duration
      passive stretch, and exercise plus long-duration passive stretch. All subjects
      had a 4-week course of exercises. In addition, subjects in the short-duration
      stretch plus exercise group completed 6 minutes of stretching per day, and
      subjects in the long-duration stretch plus exercise group completed 30 minutes of
      stretching per day. MAIN OUTCOME MEASURES: Lower Extremity Functional Scale and
      passive dorsiflexion range of motion with the knee bent and straight at baseline,
      and at 4 weeks and 3 months postintervention. RESULTS: One hundred thirty-nine
      (93%) subjects completed the 4-week assessment and 134 (89%) subjects completed
      the 3-month assessment. There were no statistically significant or clinically
      important between-group differences for the primary outcomes. CONCLUSIONS: The
      addition of passive stretching confers no benefit over exercise alone for the
      treatment of plantarflexion contracture after cast immobilization for ankle
      fracture.

PMID- 15954050
TI  - Effect of intrathecal baclofen bolus injection on temporospatial gait
      characteristics in patients with acquired brain injury.
AB  - OBJECTIVE: To evaluate changes in temporospatial gait parameters after
      intrathecal baclofen (ITB) bolus administration in patients with spasticity
      resulting from acquired brain injury by using computerized gait analysis. DESIGN:
      Case series; before-after intervention. Walking performance and spasticity in
      lower-extremity muscles were assessed before and at 2, 4, and 6 hours after ITB
      bolus injection. SETTING: Tertiary care free-standing rehabilitation hospital.
      PARTICIPANTS: Consecutive sample of 28 adults with acquired brain injury due to
      stroke, trauma, or anoxia. INTERVENTION: A 50-microg ITB bolus injection (2
      subjects received 75 microg and 100 microg, respectively). MAIN OUTCOME MEASURES:
      Ashworth Scale scores, self-selected gait velocity, stride length, cadence, step
      length symmetry, step width, and percentage of single support on the more
      involved side. RESULTS: Ashworth score decreased from 2.0+/-0.5 at baseline to
      1.3+/-0.3 at peak response ( P <.001), whereas gait velocity increased from 41+/
      26 to 47+/-31 cm/s ( P <.001). Significant improvements also occurred in stride
      length ( P <.05) and step width ( P <.001). Gait velocity was the most sensitive
      temporospatial outcome measure for differentiating functional response to ITB
      bolus injection. Sixteen patients increased velocity by an average of 12 cm/s,
      representing a mean gain of 33% over their baseline walking speed, while 5
      decreased (mean loss, -6 cm/s [52% of baseline]) and 7 were unchanged. There was
      a significant correlation between baseline velocity and peak change in velocity
      after ITB bolus ( r =.39, P <.05). Baseline Ashworth score correlated inversely
      with velocity, stride length, cadence, and percentage single support (r range, 
      .46 to -.57). No significant correlations were found between change in Ashworth
      score and change in any temporospatial outcome measure. CONCLUSIONS: ITB bolus
      injection consistently reduces spasticity in ambulatory patients with acquired
      brain injury but may result in a range of changes in walking performance that can
      be reliably detected using computerized motion analysis. Velocity appears to be
      the most sensitive parameter with which to classify individual patient response.
      The relation between baseline gait velocity and peak change in velocity after
      bolus administration may have application in predicting the outcome of screening
      trials for pump implantation; it warrants further investigation.

PMID- 15954051
TI  - The impact of severe acute respiratory syndrome on the physical profile and
      quality of life.
AB  - OBJECTIVE: To investigate the impact of severe acute respiratory syndrome (SARS)
      on the physical fitness and health-related quality of life (HRQOL) among SARS
      survivors. DESIGN: A cohort study. SETTING: An outpatient physiotherapy
      department in a major hospital in Hong Kong. PARTICIPANTS: SARS patients (N=171)
      discharged from the hospital. Their mean age was 37.36+/-12.65 years, and the
      average number of days of hospitalization was 21.79+/-9.93 days. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Subjects cardiorespiratory (6-minute walk
      test [6MWT], Chester step test for predicting maximal oxygen uptake [Vo 2 max]),
      musculoskeletal (proximal/distal muscle strength and endurance test), and HRQOL
      status (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]) were
      measured and compared with the normative data matched for age and sex. RESULTS:
      Seventy-eight (45.61%) patients continued to require prednisolone (< 0.5mg.kg -1
      .d -1 ) for residual lung opacities when data were collected. The values of 6MWT
      distance, predicted Vo 2 max, proximal and distal muscle strength, and the scores
      from all SF-36 domains, particularly perceived role-physical, were significantly
      lower than the normative data ( P <.05). CONCLUSIONS: SARS survivors had deficits
      in cardiorespiratory and musculoskeletal performance, and their HRQOL appeared to
      be significantly impaired.

PMID- 15954052
TI  - Factor structure of the pain disability index in workers compensation claimants
      with low back injuries.
AB  - OBJECTIVE: To examine the factor structure of a telephone-administered Pain
      Disability Index (PDI) and the effects of race and sex on the PDI. DESIGN:
      Computer-assisted telephone interviews of a cohort with occupational low back
      injuries. SETTING: General community. PARTICIPANTS: Missouri workers compensation
      claimants (N=1329) with low back injuries. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: PDI, levels of pain severity, Social Security Disability
      Insurance status, and the Fear-Avoidance Behavior Questionnaire. RESULTS: Results
      for the total sample and by race/sex group indicated support for a 2-factor model
      of the PDI corresponding to voluntary activities (eg, social, occupational,
      recreational) and obligatory activities (eg, activities of daily living, eating,
      sleeping). Additional psychometric analyses of the voluntary and obligatory
      subscales indicated adequate reliability and construct validity overall and in
      each of the race/sex groups. African Americans reported more pain-related
      disability on both subscales than whites. Women reported more disability on the
      voluntary subscale than men. CONCLUSIONS: The results support use of the PDI as a
      bidimensional measure of pain-related disability, with strong psychometric
      properties. They also support its administration by telephone.

PMID- 15954053
TI  - Cognitive complaints are associated with depression, fatigue, female sex, and
      pain catastrophizing in patients with chronic pain.
AB  - OBJECTIVE: To examine the relation between demographic, pain-related,
      psychosocial, affective, and treatment factors and complaints of cognitive
      dysfunction among patients with chronic pain. DESIGN: Cross-sectional survey.
      SETTING: A university hospital outpatient multidisciplinary chronic pain program.
      PARTICIPANTS: Chronic pain patients (N=222; 135 women, 87 men) completed a
      battery of psychometric questionnaires as part of an initial evaluation on
      referral to the program. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Cognitive impairment was assessed with items from the Brief Symptom Inventory;
      measures of depressive symptoms, pain intensity, posttraumatic stress disorder
      (PTSD), and pain catastrophizing were obtained from the Beck Depression Inventory
      (negative affect, negative self, somatic/physical function), McGill Pain
      Questionnaire, Modified Posttraumatic Chronic Pain Test, and Coping Strategies
      Questionnaire, respectively; and measures of subjective sleep disturbance,
      fatigue, opiate use, compensation/litigation status, pain location, and relevant
      demographic data were obtained from an open-ended questionnaire. RESULTS:
      Correlational analysis indicated that female sex, pain intensity, PTSD symptoms,
      depressive symptoms, catastrophizing, pain location (neck), and fatigue were all
      positively related to cognitive complaints. Simultaneous regression analysis
      showed that all factors combined accounted for 52% of the variance in self-report
      of cognitive difficulties and that 6 variables had a significant unique
      contribution to the report of cognitive complaints in the following order of
      importance: depression-negative affect (beta=.28, P <.05), fatigue (beta=.17, P
      <.05), depression-somatic/physical function (beta=.16, P <.05), depression
      negative self (beta=.14, P =.05), pain catastrophizing (beta=.12, P =.08), and
      female sex (beta=.12, P <.05). CONCLUSIONS: Complaints of cognitive impairment
      among chronic pain patients appear to be associated with multiple factors, with
      particular attention to depressive symptoms, fatigue, and catastrophizing. Our
      results also suggest that women with chronic pain are particularly vulnerable to
      cognitive dysfunction.

PMID- 15954054
TI  - Chronic pain in persons with neuromuscular disease.
AB  - OBJECTIVE: To examine the nature and scope of pain in persons with neuromuscular
      disorder (NMD). DESIGN: Survey study. SETTING: University-based rehabilitation
      research programs. PARTICIPANTS: Adults with NMD (N=193). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Pain presence or absence, pain severity, pain
      quality (Neuropathic Pain Scale), pain interference (Brief Pain Inventory), pain
      site, quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey
      [SF-36]), and pain treatment. RESULTS: Seventy-three percent of the sample
      reported pain, with 27% of these reporting that this pain was severe (> or =7 on
      a 0-10 scale), on average. "Deep," "tiring," "sharp," and "dull" were the words
      used most frequently to describe NMD pain. Patients with amyotrophic lateral
      sclerosis and myotonic muscular dystrophies reported the greatest pain
      interference, and patients with Charcot-Marie-Tooth the least, among all NMD
      diagnoses. The most frequent pain site, overall, was back (49%), followed by leg
      (47%), shoulder (43%), neck (40%), buttock and hip(s) (37%), feet (36%), arm(s)
      (36%), and hand(s) (35%). The study participants reported significantly greater
      dysfunction than subjects in the SF-36 normative sample (persons without health
      problems) on a number of the SF-36 scales. However, we found no significant
      differences between the study participants and the US norms on the SF-36 role
      emotional or mental health scales. A number of pain treatments were used by the
      study sample, but no treatment appeared to be effective for all participants, and
      some of the treatments reported as most effective (eg, chiropractic care) were
      used by very few participants. CONCLUSIONS: Pain is a common problem among
      patients with NMDs. There are many similarities, but also some important
      differences, between NMD diagnostic groups on the nature and scope of pain and
      its impact. More research is needed to identify and test effective treatments for
      NMD-related pain.

PMID- 15954055
TI  - Current use of lumbar traction in the management of low back pain: results of a
      survey of physiotherapists in the United Kingdom.
AB  - OBJECTIVE: To identify the current use of traction and the types of patients,
      treatment parameters, and treatment modalities used in conjunction with traction.
      DESIGN: Postal survey, with 4 sections: professional characteristics of
      respondent, current use of traction, patient selection, and treatment parameters.
      SETTING: Musculoskeletal outpatient departments (private and nonprivate
      practitioners). PARTICIPANTS: Random sample (N=1491) of chartered
      physiotherapists in the UK who work in the management of low back pain (LBP).
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Descriptive analysis of
      information on current use and practice in applying traction. RESULTS: A response
      rate of 83% (n=1239) was achieved; 41% (n=507) use lumbar traction, which is most
      commonly used in the management of subacute LBP patients presenting with nerve
      root symptoms. Treatment parameters were established for weights (5-60 kg),
      frequency (2-3 times weekly), and length of treatment (4 wk). In addition,
      traction is commonly used with other modalities (87%): mobilizations, advice, and
      exercise. CONCLUSIONS: Survey results show the continued use of lumbar traction
      despite the recommendations of numerous guidelines. Results also clarify the
      types of patients and the parameters used in the application of traction.

PMID- 15954056
TI  - Exercise prescription in subjects with spinal cord injuries.
AB  - OBJECTIVE: To evaluate the effect of training with ergometers on subjects with
      spinal cord injury (SCI) in the postacute phase. DESIGN: Cohort study. SETTING: A
      spinal unit at a physical medicine and rehabilitation institute. PARTICIPANTS:
      Twenty-one subjects with SCI in the postacute phase as a consecutive sample were
      chosen on a strict first-come, first-chosen basis. All patients completed the
      study. INTERVENTIONS: A 6-week (5d/wk, 90 min/d) program consisting of exercises
      with the ergometers formulated (as intensity and duration) for each patient on
      the basis of the results obtained in specific cardiovascular tests. MAIN OUTCOME
      MEASURES: Parameters of workload levels, as well as hematologic and hormonal
      parameters, recorded during the first 6 weeks of training. RESULTS: The workload
      performed during the training showed an initial increase, but it reached a
      plateau in week 4. No statistically meaningful variations in the workload emerged
      between the fourth and the sixth weeks of monitoring. There were no hematologic
      or hormonal signs of overtraining. CONCLUSIONS: Strengthening and aerobic
      rehabilitation programs for patients with subacute SCI should be limited to 4
      weeks, followed by an independent maintenance exercise program. The strengthening
      program is safe for these patients.

PMID- 15954057
TI  - Fitness, inflammation, and the metabolic syndrome in men with paraplegia.
AB  - OBJECTIVE: To determine the relations among peak aerobic capacity, physical
      activity, functional ability, components of the metabolic syndrome (high-density
      lipoprotein cholesterol [HDL-C], triglycerides [TG], glucose, insulin, abdominal
      obesity, high blood pressure), and inflammatory factors (interleukin-6 [IL-6], C
      reactive protein [CRP]) in men with paraplegia. DESIGN: Cross-sectional
      exploratory design. SETTING: University research laboratory. PARTICIPANTS: Twenty
      two men (age, 39+/-9y; duration of injury, 17+/-9y; level of injury, T2-L2) with
      functionally complete paraplegia volunteered to participate. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Peak aerobic capacity was measured using a
      graded peak exercise test with an arm ergometer, and physical activity was
      assessed by the Physical Activity and Disability Scale. Functional ability was
      assessed by the Self-Report Functional Measure. Circulating glucose, insulin, HDL
      C, TG, total cholesterol, IL-6, and CRP levels were determined by specific enzyme
      or immunologic assays. Body fat was determined by dual-energy x-ray
      absorptiometry, and central obesity was estimated from abdominal sagittal
      diameters. RESULTS: Lower peak aerobic capacities were associated with lower HDL
      C and lower physical activity levels ( P <.014). Lower physical activity levels
      were associated with higher fasting glucose, lower HDL-C level, and larger
      abdominal sagittal diameters ( P <.036). Larger abdominal sagittal diameters were
      associated with higher fasting glucose, higher fasting and postload insulin,
      lower HDL-C, higher TG, and higher CRP levels ( P <.05). CONCLUSIONS: Diet and
      exercise trials are needed to determine the efficacy and effectiveness of
      lifestyle interventions aimed at slowing the progression of the metabolic
      syndrome in people with spinal cord injury.

PMID- 15954058
TI  - Predictors of psychosocial adaptation among people with spinal cord injury or
      disorder.
AB  - OBJECTIVE: To examine the influence of disability-related medical and psychologic
      variables on psychosocial adaptation to spinal cord injury or disorder (SCI/D).
      DESIGN: A structural equation modeling design linking 3 sets of predictive
      variables to an outcome measure of adaptation. SETTING: Two outpatient SCI
      clinics (1 veteran, 1 civilian) in Texas. PARTICIPANTS: Veterans (n=181) and
      civilians (n=132) with SCI/D. INTERVENTIONS: Not applicable. MAIN OUTCOME
      MEASURES: The adaptation outcome was measured by 2 subscales (acknowledgment,
      adjustment) of the Reactions to Impairment and Disability Inventory (RIDI) and by
      the Quality of Life Scale. The predictive variables were measured by a
      demographic questionnaire, 3 subscales (intrusion, re-experiencing, hyperarousal)
      of the Purdue Posttraumatic Stress Disorder-Revised scale, the McMordie-Templer
      Death Anxiety Scale, and 3 subscales (anxiety, depression, denial) of the RIDI.
      RESULTS: Goodness-of-fit indices suggested that a revised model of adaptation was
      a moderately good fit to the data. The revised model of adaptation indicated that
      there were medium total effects (direct plus indirect) on psychosocial adaptation
      by 2 latent variables (disability severity and impact, negative affectivity) and
      small total effects on psychosocial adaptation by disengagement coping. The
      latent factor of disengagement coping had the strongest direct effect on
      adaptation (although not statistically significant). Disability severity and
      impact had medium indirect effects and negative affectivity had small indirect
      effects on psychosocial adaptation. All of the aforementioned effects had a
      negative coefficient. CONCLUSIONS: Negative emotional responses (eg, depression,
      anxiety) to SCI/D, disengagement-type coping (eg, disability denial, avoidance),
      and the severity and impact of disability were related to lower levels of
      adaptation to SCI/D.

PMID- 15954059
TI  - A longitudinal evaluation of sleep and breathing in the first year after cervical
      spinal cord injury.
AB  - OBJECTIVES: To establish the incidence of sleep disordered breathing (SDB) after
      acute tetraplegia and to determine the relation between the Apnea-Hypopnea Index
      (AHI) score and the previously postulated predictors of SDB in tetraplegia.
      DESIGN: Inception cohort. We performed full polysomnography immediately after
      acute tetraplegia and at 2, 4, 13, 26, and 52 weeks postinjury. Spirometry,
      maximum inspiratory and expiratory pressures, medication usage, and neck and
      abdominal girth were also assessed. Preinjury SDB was estimated using the
      multivariate apnea prediction equation. SETTING: Acute care, subacute care, and
      community. PARTICIPANTS: Consecutive sample with acute tetraplegia. Thirty
      subjects (25 men) were initially included. Thirteen completed 12 months of follow
      up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SDB (AHI score >10
      events/h) and respiratory function. RESULTS: Three subjects (10%; 95% confidence
      interval [CI], 2%-28%) had probable SDB before injury. In the first 48 hours
      after injury, no subject had SDB. At 2 weeks, 60% (95% CI, 26%-88%) had SDB; at 4
      weeks, 62% (95% CI, 38%-82%); at 13 weeks, 83% (95% CI, 61%-95%); at 26 weeks,
      68% (95% CI, 44%-88%); and at 52 weeks, 62% (95% CI, 32%-86%). No consistent
      relation was found between the previously postulated predictors and SDB.
      CONCLUSIONS: SDB is highly prevalent within 4 weeks of acute tetraplegia.

PMID- 15954060
TI  - Combined intercostal and diaphragm pacing to provide artificial ventilation in
      patients with tetraplegia.
AB  - OBJECTIVE: To evaluate the usefulness of combined intercostal and diaphragm
      pacing to maintain independence from mechanical ventilation. DESIGN: A
      prospective trial. SETTING: Clinical research center at a large tertiary
      hospital. PARTICIPANTS: Four ventilator-dependent subjects with spinal cord
      injury with only unilateral phrenic nerve function. INTERVENTION: During an
      initial surgical procedure, a multipolar epidural disk electrode was positioned
      on the ventral surface of the upper-thoracic spinal cord via a hemilaminectomy to
      activate the inspiratory intercostal muscles. A phrenic nerve electrode was
      implanted unilaterally via the thoracic approach. MAIN OUTCOME MEASURES: Inspired
      volume production and duration that subjects could be comfortably maintained when
      off mechanical ventilatory support. RESULTS: Initial maximum inspired volumes
      from combined intercostal and diaphragm stimulation ranged between .23 and .93L
      and significantly increased over the course of reconditioning period to between
      0.55 and 1.31L; subjects could be maintained off mechanical ventilation between
      16 and 24 hours a day. CONCLUSIONS: Combined intercostal and unilateral diaphragm
      pacing may be a useful therapeutic modality capable of maintaining long-term
      ventilatory support in patients with only unilateral phrenic nerve function.

PMID- 15954061
TI  - Pressure ulcer prevalence in people with spinal cord injury: age-period-duration
      effects.
AB  - OBJECTIVE: To examine age-period-duration patterns of the prevalence of pressure
      ulcers in community-residing people with spinal cord injury (SCI). DESIGN:
      Multicenter cohort study. SETTING: Nine Model Spinal Cord Injury Systems
      throughout the United States. PARTICIPANTS: People with SCI (N=3361) injured
      between 1986 and 1995 and followed up thereafter on a yearly basis through 2002.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Physician-confirmed pressure
      ulcers of stage II or greater at the follow-up visits. RESULTS: The multivariable
      generalized estimating equations model showed a significant trend toward
      increasing pressure ulcer prevalence in the recent years (1994-2002 vs 1984-1993:
      odds ratio=1.4; 95% confidence interval, 1.2-1.6) not explained by aging, years
      since injury, or demographic and clinical factors. The risk of pressure ulcers
      appeared to be steady during the first 10 years and increased 15 years
      postinjury. Pressure ulcers were more common among the elderly, men, African
      Americans, singles, subjects with education less than high school, unemployed,
      subjects with complete injury, and subjects with history of pressure ulcers,
      rehospitalization, nursing home stay, and other medical conditions. Injury cause
      and level had no significant effect. CONCLUSIONS: These results highlight the
      need for research into factors that contribute to the increasing pressure ulcer
      prevalence.

PMID- 15954062
TI  - Mechanical load on the upper extremity during wheelchair activities.
AB  - OBJECTIVE: To determine the net moments on the glenohumeral joint and elbow joint
      during wheelchair activities. DESIGN: Kinematics and external forces were
      measured during wheelchair activities of daily living (level propulsion, riding
      on a slope, weight-relief lifting, reaching, negotiating a curb) and processed in
      an inverse dynamics biomechanic model. SETTING: Biomechanics laboratory.
      PARTICIPANTS: Five able-bodied subjects, 8 subjects with paraplegia, and 4
      subjects with tetraplegia. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE:
      Net moments on the glenohumeral joint and elbow joint. RESULTS: Peak shoulder and
      elbow moments were significantly higher for negotiating a curb and weight-relief
      lifting than for reaching, level propulsion, and riding on a slope. Overall, the
      elbow extension moments were significantly lower for subjects with tetraplegia
      than for those with paraplegia. CONCLUSIONS: The net moments during weight-relief
      lifting and negotiating a curb were high when compared with wheelchair propulsion
      tasks. Taking the effect of frequency and duration into account, these loads
      might imply a considerable risk for joint damage in the long term.

PMID- 15954063
TI  - Impact of sitting time on seat-interface pressure and on pressure mapping with
      multiple sclerosis patients.
AB  - OBJECTIVE: To examine changes in seat-interface pressure with multiple sclerosis
      (MS) patients. DESIGN: Case series. SETTING: Multiple Sclerosis Society's
      Resource Centre and community. PARTICIPANTS: Convenience sample of 15 MS
      wheelchair users and 12 MS non-wheelchair users. INTERVENTION: Interface pressure
      was measured for 8 minutes using the Force Sensing Array pressure mapping system.
      MAIN OUTCOME MEASURES: Number of activated sensors, standard deviation, average
      and maximum pressures. RESULTS: With the wheelchair users, significant decreases
      were found in the standard deviation and average and maximum pressures during 0
      to 2 minutes of sitting ( P <.01). Average pressure was the only parameter to
      show a significant decrease in the non-wheelchair users ( P <.01) during 0 to 2
      minutes. Significant increases were found in all output parameters during 2 to 4
      minutes with both groups ( P <.05). Non-wheelchair users showed no significant
      changes in the output parameters after 4 minutes, but wheelchair users showed
      significant continued increases in the output parameters from 4 to 8 minutes ( P
      <.05). CONCLUSIONS: Because no significant changes in interface pressure occurred
      after 4 minutes of sitting with the non-wheelchair users, 4 minutes may be a
      reasonable sitting time before interface pressure is recorded with this group.
      Significant changes in interface pressure continued up to 8 minutes with the
      wheelchair users, therefore 8 minutes or beyond may be a reasonable sitting time
      before recording with this group.

PMID- 15954064
TI  - Ballism after stroke responds to standard physical therapeutic interventions.
AB  - OBJECTIVE: To report the effects of noninvasive standard physical therapy (PT)
      interventions on an involuntary movement disorder after stroke. DESIGN: Single
      case with clinical follow-up over 2 years. SETTING: Inpatient stroke and
      rehabilitation services and outpatient clinic. PARTICIPANT: A man with acute
      bilateral ballism after unilateral subthalamic infarction. INTERVENTIONS:
      Rhythmic coordinated bilateral limb movements and firm tactile stimulation to the
      hand. MAIN OUTCOME MEASURES: We had not anticipated that dyskinesia itself would
      specifically improve during treatment. Consequently, we used qualitative clinical
      observations, including review of videotaped performance, and self-reported limb
      control. Hypotheses concerning treatment effects were developed after data
      collection. RESULTS: Involuntary movements recurrently improved within treatment
      sessions. CONCLUSIONS: PT may improve dyskinesia after stroke. The benefit may be
      adjunctive or alternative to current invasive treatments of movement disorders
      after brain injury and merits confirmation. The improvements are consistent with
      current research indicating that (1) intact cortical, subcortical, cerebellar,
      and spinal areas interact to generate bilateral rhythmic limb movements that can
      overcome dyskinesia and (2) tactile stimulation can improve motor deficits
      associated with basal ganglia disorders. Finally, because functional activities
      assessments improved our evaluation of ballism, these should be routinely used
      along with conventional neurologic examination to assess involuntary movement
      disorders.

PMID- 15954065
TI  - Proposal and validation of a new functional ambulation classification scale for
      clinical use.
AB  - OBJECTIVE: To validate a new functional ambulation classification. DESIGN:
      Validity study. SETTING: In- and outpatients of a district hospital
      rehabilitation service. PARTICIPANTS: Thirty-one patients with poststroke
      hemiplegic gait disorders compared with a control group of 5 healthy people.
      Interventions Not applicable. MAIN OUTCOME MEASURES: Three independent examiners
      assessed the functional ambulation levels of each patient in blind trials.
      Interrater reliability was analyzed among the examiners. Walking velocity (slow,
      normal, fast) was measured with a manual chronometer, and the number of steps
      taken over a 48-hour period was recorded with a step counter. The linear
      correlation was calculated from among functional level classification, walking
      velocity, and the number of steps taken. RESULTS: There was a good interrater
      reliability among the examiners (kappa=.74). A significant association and a
      linear correlation were found between functional ambulation level, walking
      velocity, and the number of steps taken. CONCLUSIONS: The proposed classification
      is reliable and valid for determining the different levels of walking abilities.

PMID- 15954066
TI  - Walking recovery after an acute stroke: assessment with a new functional
      classification and the Barthel Index.
AB  - OBJECTIVES: To investigate walking recovery after an acute stroke by using both a
      new functional classification and the Barthel Index, and to identify factors
      associated with good recovery. DESIGN: A 1-year inception cohort study. SETTING:
      In- and outpatient setting in a district hospital. PARTICIPANTS: Twenty-six
      patients with a prognosis of intermediate walking recovery. INTERVENTION:
      Conventional physical rehabilitation under professional supervision. MAIN OUTCOME
      MEASURES: Walking capacity was assessed with a new classification scale and the
      Barthel Index during 5 patient evolution stages (admission to the hospital,
      hospital and physiotherapy discharge, clinical review, end of study). We also
      assessed the severity of the paresis of the affected lower limb, the time lapse
      between the stroke until the recovery of the weight-bearing capacity of the
      affected leg, and finally the time until standing balance was regained. RESULTS:
      We detected improvement in walking capacity throughout the follow-up process with
      our new classification scale, but not with the Barthel Index. Significant
      improvements were observed from the initial assessment, from 1 month onward, and
      from 3 to 12 months. The functional level of the final ambulation correlated
      negatively and significantly with the initial time to achieve weight-bearing
      capacity on the affected leg and also with the standing balance. There was also a
      significant correlation with the severity of lower-extremity paresis.
      CONCLUSIONS: Patients experienced an improvement in walking recovery throughout
      the first year after their stroke. The early weight-bearing capacity of the
      affected leg and standing balance were associated with higher walking levels 1
      year after the stroke.

PMID- 15954067
TI  - A comparison of changes in rhythms of sacral skin blood flow in response to
      heating and indentation.
AB  - OBJECTIVE: To differentiate blood flow control mechanisms associated with
      indentation from those associated with heating and to discern heat-induced and
      pressure-induced changes by comparing the effect of externally applied stress on
      skin blood flow (SBF) to the response to externally applied heat. DESIGN:
      Repeated-measures design. SETTING: A university research laboratory.
      PARTICIPANTS: Ten healthy, young adults (5 men, 5 women; mean age +/- standard
      deviation, 30.0+/-3.1y). Intervention Incremental heat (35 degrees -45 degrees C,
      1 degrees step/min) and pressure (0-60 mmHg, 5 mmHg step/3 min) on the sacrum
      using a computer-controlled indenter. Sessions for heat and pressure protocols
      were separated by 7+/-2 days. MAIN OUTCOME MEASURES: We used a Laserflo Blood
      Perfusion Monitor 2 and Softip pencil probe to measure capillary blood perfusion
      and wavelet analysis to decompose the blood flow signal. The power spectrum was
      divided into 5 ranges corresponding to metabolic, neurogenic, myogenic,
      respiratory, and cardiac control mechanisms. The average relative (ie,
      normalized) power in each frequency range was computed to determine of the
      relative contribution of each control mechanism. RESULTS: Power in the myogenic
      frequency range was higher after incremental pressure and lower after incremental
      heating, whereas power in the metabolic frequency range was lower after
      incremental pressure and higher after incremental heating ( P <.01). Mean blood
      flow decreased as pressure increased from 0 to 15 mmHg; mean blood flow increased
      as pressure increased from 15 to 60 mmHg. CONCLUSIONS: SBF, as recorded by the
      laser Doppler, suggests that there may be a myogenic control mechanism mediating
      blood flow after incremental tissue loads and that a metabolic control mechanism
      may mediate blood flow after heat application to the tissue. The study of local
      blood flow control mechanisms and their response to pathomechanical perturbations
      may be possible using wavelet analysis of blood flow oscillations. More research
      is needed to establish the clinical utility of these findings in the development
      of support surfaces intended to reduce the risk of developing pressure ulcers.

PMID- 15954068
TI  - The effect of real and sham acupuncture on thermal sensation and thermal pain
      thresholds.
AB  - OBJECTIVE: To compare the effect of real and sham acupuncture and a control
      intervention on thermal sensation and thermal pain thresholds. DESIGN: Single
      blind, randomized controlled, repeated-measures trial. SETTING: Laboratory.
      PARTICIPANTS: Eighteen acupuncture-naive, healthy subjects with no history of
      upper-limb pathology or acupuncture contraindications. INTERVENTION: Subjects
      were randomly assigned (blind card allocation) to 1 of 6 possible orders of
      application of the interventions, which consisted of 25 minutes each of control,
      real, and sham acupuncture. MAIN OUTCOME MEASURES: Thermal sensation and thermal
      pain thresholds measured with a thermal sensory analyzer before and after each
      intervention. RESULTS: There were increases in cold and hot pain and cold
      sensation thresholds with real acupuncture. The level of increase did not differ
      significantly from the changes that occurred with sham acupuncture and control
      interventions. CONCLUSIONS: Although we observed a trend toward a decreased
      sensitivity to thermal pain and thermal sensation with real acupuncture, this
      trend did not differ significantly from the changes with control or sham
      interventions. Therefore, no support was provided for analgesic or placebo
      effects of acupuncture. The trend, combined with the relatively low power of the
      inferential tests applied does, however, suggest that further research is
      merited.

PMID- 15954069
TI  - Femoral neuropathy due to patellar dislocation in a theatrical and jazz dancer: a
      case report.
AB  - This case report describes a teenage female, high-level modern dancer who
      suffered multiple left patellar dislocations. Her history is atypical in that
      after her fifth dislocation, her recovery was hindered secondary to persistent
      weakness and atrophy of her quadriceps out of proportion to disuse alone.
      Electrodiagnostic studies and magnetic resonance imaging showed evidence of a
      subacute femoral neuropathy correlating chronologically with her most recent
      patellar dislocation. This case suggests that further diagnostic study may be
      warranted in patients with persistent quadriceps weakness or atrophy after a
      patellar dislocation, because this may suggest the presence of a femoral
      neuropathy. This is important because the strength training goals and precautions
      differ in disuse atrophy and a neuropathy. We believe this is the first reported
      case of a femoral neuropathy associated with the mechanism of a patellar
      dislocation.

PMID- 15954070
TI  - Psychogenic and pharmacologic induction of the let-down reflex can facilitate
      breastfeeding by tetraplegic women: a report of 3 cases.
AB  - Although an increasing number of women are becoming pregnant and rearing children
      after spinal cord injury (SCI), scant literature exists on breastfeeding after
      injury. In particular, it is unclear whether women with SCI above T7 can sustain
      breastfeeding in a manner similar to neurologically intact nursing mothers. A
      functional let-down reflex is required to provide adequate milk to a nursing
      infant. Infant suckling activates tactile receptors in the breast, and this
      signal is carried via afferent nerves in the T4-6 dorsal roots to the spinal cord
      and then to neurons in the hypothalamus, which release oxytocin into the
      bloodstream. Oxytocin triggers milk ejection from the breast. Suckling-induced
      afferent stimuli are absent in women with SCI above T4 and are reduced if the
      injury is between T4 and T6. This report describes the breastfeeding practices of
      3 tetraplegic women and shows that breastfeeding can be maintained for extended
      periods (12-54 wk) after delivery. Two women required active mental imaging and
      relaxation techniques, or oxytocin nasal spray, to facilitate the let-down
      reflex. These findings suggest that although an absence of suckling-induced
      afferent stimuli may impair the let-down reflex, long-term breastfeeding can be
      maintained.

PMID- 15954071
TI  - One rare side effect of zolpidem--sleepwalking: a case report.
AB  - Zolpidem is an imidazopyridine agent indicated for the short-term treatment of
      insomnia. Sleepwalking is a rare side effect of zolpidem. A review of the
      literature produced only 2 cases. We report a case of a male rehabilitation
      inpatient in his mid fifties with a history of alcoholism and traumatic brain
      injury who had undergone a right hip hemiarthroplasty. He had no history of
      somnambulism or insomnia but walked in his sleep on 2 nonconsecutive nights after
      taking zolpidem. He had exhibited no such behavior before taking zolpidem, on the
      intervening night that was he was not given medication, and after the medication
      was discontinued. We conclude that zolpidem can cause sleepwalking, and patients
      who have suffered a brain injury may be more susceptible to this side effect.
      Here we describe the clinical presentation and review the relevant literature on
      zolpidem and sleepwalking.

PMID- 15954072
TI  - Assessing paratransit eligibility under the Americans With Disabilities Act in
      the rehabilitation setting.
AB  - OBJECTIVE: To assess the usefulness of a rehabilitation-based assessment program
      designed to determine the eligibility, according to Americans With Disabilities
      Act criteria, of applicants for paratransit bus services. DESIGN: Retrospective
      summary statistics on 500 consecutive paratransit evaluations. SETTING:
      Outpatient physical medicine and rehabilitation center. PARTICIPANTS: Applicants
      for a community paratransit bus service. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Clinical assessment of each applicants functional physical and
      cognitive ability to ride a fixed-route or paratransit bus system. RESULTS: Of
      the 500 applicants for specialized paratransit services, 38 (8%) were found to be
      ineligible, based on rehabilitation professionals evaluations of their physical
      and cognitive abilities. CONCLUSIONS: Mass transit organizations must adjust to
      the rapidly growing demand for paratransit services. Rehabilitation-based
      assessment programs, because of the expertise they provide in assessing
      functional abilities, are uniquely qualified to provide objective determinations
      of paratransit eligibility.

PMID- 15954073
TI  - The role of subacromial shoulder irrigation in the treatment of calcific rotator
      cuff tendinosis: a case series.
AB  - OBJECTIVE: To study the efficacy of subacromial shoulder irrigation in the
      treatment of calcific rotator cuff tendinosis. DESIGN: Consecutive case series.
      SETTING: Musculoskeletal rehabilitation clinic. PARTICIPANTS: Twenty-eight tennis
      players (16 women, 12 men; mean age, 44.3y) with calcific rotator cuff
      tendinosis, who failed conservative measures. INTERVENTION: Subjects underwent
      fluoroscopically guided subacromial shoulder irrigation (50-75 mL of normal
      saline in 10 mL aliquots) followed by a corticosteroid injection (5 mL solution
      of 1 mL triamcinolone [40 mg/mL] and 4 mL of 0.5% bupivacaine). After the
      procedure, all patients completed the same exercise regimen. MAIN OUTCOME
      MEASURES: LInsalata Shoulder Rating Questionnaire (LSRQ) score, visual numeric
      pain score, and patient satisfaction. RESULTS: At 1-year follow-up, 85.7%
      reported a successful outcome with significant improvements in the LSQR and
      numeric pain scores. CONCLUSIONS: Our minimally invasive approach was safe, well
      tolerated, and effective, which should make it useful in providing relief for
      patients with rotator cuff tendinosis.

PMID- 15954074
TI  - The prevalence of knee pain and symptomatic knee osteoarthritis among veteran
      traumatic amputees and nonamputees.

PMID- 15954076
TI  - Rapid dissolution of cellulose in LiOH/urea and NaOH/urea aqueous solutions.
AB  - Rapid dissolution of cellulose in LiOH/urea and NaOH/urea aqueous solutions was
      studied systematically. The dissolution behavior and solubility of cellulose were
      evaluated by using (13)C NMR, optical microscopy, wide-angle X-ray diffraction
      (WAXD), FT-IR spectroscopy, DSC, and viscometry. The experiment results revealed
      that cellulose having viscosity-average molecular weight ((overline) M eta) of
      11.4 x 104 and 37.2 x 104 could be dissolved, respectively, in 7% NaOH/12% urea
      and 4.2% LiOH/12% urea aqueous solutions pre-cooled to -10 degrees C within 2
      min, whereas all of them could not be dissolved in KOH/urea aqueous solution. The
      dissolution power of the solvent systems was in the order of LiOH/urea >
      NaOH/urea >> KOH/urea aqueous solution. The results from DSC and (13)C NMR
      indicated that LiOH/urea and NaOH/urea aqueous solutions as non-derivatizing
      solvents broke the intra- and inter-molecular hydrogen bonding of cellulose and
      prevented the approach toward each other of the cellulose molecules, leading to
      the good dispersion of cellulose to form an actual solution.

PMID- 15954077
TI  - Comparing data mining methods on the VAERS database.
AB  - PURPOSE: Data mining may enhance traditional surveillance of vaccine adverse
      events by identifying events that are reported more commonly after administering
      one vaccine than other vaccines. Data mining methods find signals as the
      proportion of times a condition or group of conditions is reported soon after the
      administration of a vaccine; thus it is a relative proportion compared across
      vaccines, and not an absolute rate for the condition. The Vaccine Adverse Event
      Reporting System (VAERS) contains approximately 150 000 reports of adverse events
      that are possibly associated with vaccine administration. METHODS: We studied
      four data mining techniques: empirical Bayes geometric mean (EBGM), lower-bound
      of the EBGM's 90% confidence interval (EB05), proportional reporting ratio (PRR),
      and screened PRR (SPRR). We applied these to the VAERS database and compared the
      agreement among methods and other performance properties, particularly focusing
      on the vaccine-event combinations with the highest numerical scores in the
      various methods. RESULTS: The vaccine-event combinations with the highest
      numerical scores varied substantially among the methods. Not all combinations
      representing known associations appeared in the top 100 vaccine-event pairs for
      all methods. CONCLUSIONS: The four methods differ in their ranking of vaccine
      COSTART pairs. A given method may be superior in certain situations but inferior
      in others. This paper examines the statistical relationships among the four
      estimators. Determining which method is best for public health will require
      additional analysis that focuses on the true alarm and false alarm rates using
      known vaccine-event associations. Evaluating the properties of these data mining
      methods will help determine the value of such methods in vaccine safety
      surveillance.

PMID- 15954078
TI  - Patterns of drug use during a 15 year period: data from a Swedish county, 1988-
      2002.
AB  - PURPOSE: To present and interpret drug prescription patterns, related to various
      groups of the population in a Swedish county, in order to estimate the prevalence
      of drug use in different age groups. METHODS: Data on prescriptions, dispensed
      March-May 1988-2002, were combined with population statistics of Halland, a
      county in the south of Sweden, and analysed. Number of defined daily doses (DDD)
      per 100 inhabitants and day and prescriptions per 100 inhabitants and 3 months
      were used as indicators of drug prevalence. RESULTS: The total drug exposure in
      the population of Halland nearly doubled during the 15-year period. The most
      frequently used drugs overall, in 2002, were psycholeptics (N05), analgesics
      (N02), antibacterials (J01) and sex hormones (G03). Nearly 30% of the women of 15
      69 years were exposed to sex hormones. Multiplied drug prevalence among people
      above 60 was found for antithrombotic drugs (B01), agents acting on the renin
      angiotensin system (C09), sex hormones (G03), serum lipid reducing agents (C10),
      antidepressants (N06) and drugs for peptic ulcer and GORD (A02B). CONCLUSIONS:
      The increase in drug prescribing over the 15 years concerned both symptom-related
      treatments, like hormone replacement therapy, analgesics, antidepressants and
      drugs for acid-related disorders, as well as preventive treatments, like
      antithrombotics, lipid-lowering drugs and antihypertensives. The unit DDD/100
      inhabitants and day gives a fairly correct measure of the percentage treated for
      chronic disorders. However, for short-term treatment courses and especially for
      drug use in children, number of prescriptions/100 inhabitants and adequate period
      of time, is easier to interpret.

PMID- 15954079
TI  - Exploring the effect of transient exposure on the risk of acute events by means
      of time-window designs: an application to fluoroquinolone antibacterials and
      arrhythmia.
AB  - PURPOSE: To compare different strategies in allocating time-window at risk and in
      choosing optimal comparator in the setting of proarrhythmic effects of
      antibacterial fluoroquinolones. DESIGN: A population-based cohort study. SETTING:
      Resident population of a Northern Italian Province. PARTICIPANTS: The study
      cohort comprised 75 226 patients who received at least one prescription for
      fluoroquinolone from 1997 to 1999. Cohort members who experienced at least an
      antiarrhythmic drug prescription and/or hospitalisation with diagnosis of
      arrhythmia during the follow-up were identified. ANALYSIS: Trends in incidence
      rates of arrhythmia according to different strategies in allocating time-windows
      at risk were calculated. Standardised incidence ratios were obtained by comparing
      arrhythmic events experienced by the study cohort during the time-windows at risk
      with those expected from both external (unexposed target population) and internal
      (study cohort during reference time-windows) comparators. RESULTS: The rate of
      arrhythmia was 21.0 per 100 000 person-weeks during the in-treatment period,
      remained stable during the following week, and progressively decreased until to
      converge to 7.7 per 100 000 person-weeks from 16th weeks after stop of exposure.
      Standardised incidence ratios were 2.35 (95%CI: 1.82, 2.99) and 1.86 (1.44, 2.37)
      according to external and internal comparators respectively. Evidence of linear
      increasing of proarrhythmic effect with the length of the antibacterial therapy
      appeared from every approaches, but it was stronger by using internal comparator.
      CONCLUSIONS: Time-windows designs should be performed by allocating the time
      windows at risk and comparing outcome events observed in the cohort during these
      periods with those experienced by the same cohort during an adequate reference
      period.

PMID- 15954080
TI  - SCUD: fast structure clustering of decoys using reference state to remove overall
      rotation.
AB  - We developed a method for fast decoy clustering by using reference root-mean
      squared distance (rRMSD) rather than commonly used pairwise RMSD (pRMSD) values.
      For 41 proteins with 2000 decoys each, the computing efficiency increases nine
      times without a significant change in the accuracy of near-native selections.
      Tests on additional protein decoys based on different reference conformations
      confirmed this result. Further analysis indicates that the pRMSD and rRMSD values
      are highly correlated (with an average correlation coefficient of 0.82) and the
      clusters obtained from pRMSD and rRMSD values are highly similar (the
      representative structures of the top five largest clusters from the two methods
      are 74% identical). SCUD (Structure ClUstering of Decoys) with an automatic
      cutoff value is available at http://theory.med.buffalo.edu.

PMID- 15954081
TI  - Attaining exponential convergence for the flux error with second- and fourth
      order accurate finite-difference equations. Part 3. Application to
      electrochemical systems comprising second-order chemical reactions.
AB  - This article demonstrates that exponential convergence of the flux error can be
      attained with second- and fourth-order accurate finite difference equations even
      for such electrochemical kinetic-diffusion systems where difficult-to-resolve
      solution structures occur on account of fast second-order chemical reactions.
      Thus, as far as the flux is concerned, the simulation of some example models
      treated in the literature by means of more sophisticated adaptive grid techniques
      turns out to be as straightforward as the simulation of a simple system under
      diffusion control.

PMID- 15954082
TI  - Psychosocial factors and interleukin-6 among women with advanced ovarian cancer.
AB  - BACKGROUND: Relations among psychological stress, depression, social support, and
      interleukin-6 (IL-6, a proinflammatory cytokine) have been documented in humans
      and animals. Because elevated IL-6 is associated with a poorer prognosis among
      ovarian cancer patients and has been implicated in the metastasis of ovarian
      cancer, the current study examined relations between psychosocial factors and IL
      6 among women with advanced-stage ovarian cancer. METHODS: Sixty-one ovarian
      cancer patients completed assessments of social support, distressed mood, and
      quality of life before surgery. Peripheral blood was drawn preoperatively, and
      the plasma was assayed for IL-6. Ascites samples were also assayed for IL-6 for a
      subset of patients. RESULTS: Both IL-6 levels and distressed mood were elevated
      among patients. After statistically adjusting effects of age and disease stage,
      social attachment was associated with lower levels of IL-6 in peripheral blood (P
      = 0.03), whereas poorer health-related quality of life was associated with higher
      IL-6 (P values ranged from 0.01 to 0.03 on different measures). This pattern of
      relations was also found in the ascites. Moreover, IL-6 levels in peripheral
      blood plasma correlated significantly with IL-6 in the ascites (P < 0.001),
      suggesting that peripheral IL-6 reflects IL-6 levels at the site of the tumor.
      CONCLUSIONS: Results suggest that social support may play a protective role with
      respect to IL-6 elevations, and IL-6 may be an independent marker of health
      related quality of life among ovarian cancer patients. Processes involving IL-6
      represent possible pathways by which behavioral factors may contribute to disease
      outcomes among women with ovarian cancer.

PMID- 15954083
TI  - Does a delay in external beam radiation therapy after tissue diagnosis affect
      outcome for men with prostate carcinoma?
AB  - BACKGROUND: Physicians involved in the care of men diagnosed with prostate
      carcinoma must assess the urgency of treatment. For those men who choose external
      beam radiation therapy (EBRT), the delay from the time of biopsy to treatment may
      be stressful. There are limited data on the consequences of radiation treatment
      delay. The purpose of the current study was to evaluate the effect of time to
      treatment (TTT) on outcomes. METHODS: The authors of the current study analyzed
      1322 patients who were treated with EBRT alone. Overall survival (OS), cause
      specific survival (CSS), distant metastasis (DM), and freedom from biochemical
      failure (FFBF) were calculated. TTT was first analyzed at 4 intervals: < 3, 3-6,
      6-9 and > 9 months, and at the median TTT. Cox multivariate analysis (MVA) was
      then performed with 2002 American Joint Commission on Cancer T-stage, Gleason
      score, prostate specific antigen (PSA), radiation dose, and TTT as covariates.
      RESULTS: There were no statistical differences in OS, CSS, DM, or FFBF among men
      whose EBRT began < 3, 3-6, 6-9, or > 9 months after diagnosis. This was also true
      at the median TTT of 3.1 months. A subgroup analysis was performed in which
      patients were stratified into low-, intermediate- and high-risk groups based on
      pretreatment PSA, Gleason score and AJCC T-stage. FFBF, and DM were calculated
      above and below the median TTT of 3.1 months. In this analysis, there was no
      statistically significant difference in FFBF or DM within the risk groups.
      CONCLUSIONS: Within the limits of the current study, data indicate that a
      treatment delay, even in high-risk patients, has little effect on clinical or
      biochemical outcome.

PMID- 15954084
TI  - Postnatal development of rat pups after maternal exposure to diethanolamine.
AB  - BACKGROUND: Diethanolamine (DEA), a widely used surfactant, was administered to
      pregnant mice at the oral LD10 resulting in failure of pups to grow and thrive
      through postnatal day (PND) 3 [National Toxicology Program, 1987; York et al.,
      Teratology 37:503-504, 1988]. The toxicity profile for DEA differs among rodent
      species. This study investigated DEA-induced postnatal toxicity in a second
      species. METHODS: Timed-mated Sprague-Dawley rats were dosed (0, 50, 125, 200,
      250, or 300 mg DEA/kg/day, p.o.) on gestational days (GD) 6-19. Dams and pups
      were monitored for body weight, feed/water intake, clinical signs, litter size,
      and sex ratio. At necropsy (PND 21), maternal liver and kidney weights and number
      of uterine implantation sites were recorded. RESULTS: The high-dose group was
      terminated early due to excessive toxicity. The estimated maternal LD10 was 218
      mg/kg/day. Maternal effects included decreased body weight and relative feed
      intake (>or=200 mg/kg/day), transiently reduced relative water intake (125 and
      250 mg/kg/day), and increased absolute kidney weight (>or=125 mg/kg/day).
      Postimplantation loss (PND 0) and pup mortality (PND 0-4) were increased (>or=200
      and >or=125 mg/kg/day, respectively). Pup body weight was reduced (>or=200
      mg/kg/day) as late as PND 21. CONCLUSIONS: This study demonstrates reduced
      postnatal growth and survival in a second species after gestational exposure to
      DEA, persistence of toxic effects through the end of lactation, possibly due to
      long elimination half-life, and maternal and developmental toxicity no-observed
      adverse-effect level (NOAELs) (50 mg/kg/day) and lowest-observed-adverse-effect
      level (LOAELs) (125 mg/kg/day) for oral DEA exposure during embryo/fetal
      development in the rat.

PMID- 15954085
TI  - Prior exposure to indole-3-carbinol decreases the incidence of specific
      cyclophosphamide-induced developmental defects in mice.
AB  - BACKGROUND: Indole-3-carbinol (I3C) is a product of the hydrolysis of
      glucobrassicin that is found in cruciferous vegetables. I3C can intervene in
      toxic processes that are mediated by oxidative mechanisms because it possesses
      the chemical and pharmacokinetic properties necessary to provide a free radical
      trap. Cyclophosphamide (CP) is a bifunctional alkylating agent known to produce
      DNA damage and to cause developmental toxicity, including malformations, in
      laboratory animals. METHODS: Pregnant CD-1 mice were given a 100 mg/kg dose of
      I3C 24 or 48 hr before administration of 20 mg/kg CP on gestation day 10 (GD 10).
      Controls were given the vehicle (DMSO), I3C, or CP. This regimen was carried out
      to determine if I3C could protect against the developmental toxicity of
      alkylating agents, such as CP. Dams were sacrificed on GD 17 and their litters
      were examined for adverse effects. RESULTS: Treatment with I3C 48 hr before CP
      administration was associated with decreased fetal limb and tail malformations.
      Limb malformation incidences were reduced from 42% litters affected in the CP
      control to 16% in the I3C/CP 48-hr treatment group, and tail malformations were
      reduced from 45% in the CP control to 16% in the I3C/CP 48-hr treatment group,
      indicating a protective effect of prior exposure to I3C. I3C given 24 hr before
      CP had no significant protective effect, while having an apparently adverse
      consequence with regard to the incidence of talipes. CONCLUSIONS: Exposure of a
      developing mammal to indole-3-carbinol before exposure to cyclophosphamide during
      organogenesis can influence the teratogenicity of cyclophosphamide.

PMID- 15954086
TI  - Microarray analysis of genes in fetal central nervous system after
      ethylnitrosourea administration.
AB  - BACKGROUND: Ethylnitrosourea (ENU), a monofunctional alkylating agent, induces
      apoptosis and cell cycle arrest in neuroepithelial cells, neural stem cells in
      the fetal central nervous system (CNS). These effects occur immediately after the
      administration of ENU to pregnant animals resulting in fetal brain anomalies and
      long-term effects include brain tumors in the offspring. METHODS: Changes in gene
      expression were investigated in the fetal CNS after ENU administration to
      pregnant rats using microarray to identify the genes involved in the injury and
      recovery of the fetal CNS. RESULTS: The up-regulation of 21 genes in injury and
      15 genes in recovery phases and down-regulation of 5 genes in injury and 3 genes
      in recovery phases were identified. The genes up-regulated in the injury phase
      contained p53-target genes that mediate apoptosis and cell cycle arrest, and
      those in the recovery phase contained cell proliferation-promoting genes. The
      genes down-regulated in the injury phase contained cholesterol biosynthesis
      related genes. In addition, there were some genes that have not been identified
      to be involved in the CNS injury and recovery. CONCLUSIONS: The present study
      will provide a better understanding of the mechanisms of development,
      regeneration and carcinogenesis of the CNS as well as the mechanisms of ENU
      induced fetal CNS injury and recovery.

PMID- 15954087
TI  - Effects of hyperthermia and boric acid on skeletal development in rat embryos.
AB  - BACKGROUND: The individual effects of boric acid (BA) and hyperthermia on the
      development of the axial skeleton have been reported previously. Both cause an
      increased incidence of axial skeletal defects including a decrease in the total
      number of ribs and vertebrae. Because of the similarity in the effects of the two
      agents, we examined their interaction when given in combination to pregnant rats
      on gestational day (GD) 10. METHODS: Dams were treated on GD 10 with BA (0, 250,
      or 500 mg/kg) and hyperthermia (37, 41, or 42 degrees C) and allowed to deliver
      their pups. Doses of BA were based on results from a dose-finding study. Litters
      were evaluated on postnatal days (PND) 1 and 3 for number, gender, and weight of
      pups. On PND3, pups were examined externally and viscerally, and double-stained
      for skeletal evaluation. RESULTS: A dose-dependent, statistically significant
      increase in fetal skeletal defects was seen on PND 3 with BA or hyperthermia
      alone with even greater effects when given in combination. Defects included rib
      and vertebral fusions, split vertebral centra in the thoracic and lumbar areas,
      and a decrease in the total number of ribs and vertebrae. CONCLUSIONS: The
      increased incidence of skeletal defects resulting from combined exposure to
      hyperthermia and BA was additive for segmentation defects and synergistic for the
      reduction in numbers of vertebrae.

PMID- 15954088
TI  - Critical window of male reproductive tract development in rats following
      gestational exposure to di-n-butyl phthalate.
AB  - BACKGROUND: Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous
      environmental contaminant, has been shown to interfere with the development of
      the male reproductive tract by acting as an antiandrogen. This study was
      conducted to identify the critical days for the abnormal development of the male
      reproductive tract, specifically the testis and epididymis. METHODS: Timed
      pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation
      day (GD) 14 and 15, 15 and 16, 16 and 17, 17 and 18, 18 and 19, or 19 and 20 (GD
      0=plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and
      13, while areloa number was recorded on PND 13 only. After weaning, males were
      allowed to mature to PND 90 at which time they were necropsied. Areloa number and
      AGD were recorded and testes, epididymides, seminal vesicles, prostate gland,
      kidneys, and liver weighed. Blood serum was collected and assayed for total
      testosterone concentration. RESULTS: There were no observable effects on litter
      size, sex ratio, serum testosterone concentration, or mortality of pups.
      Statistically significant permanent reductions in AGD were seen in males exposed
      prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present
      in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20.
      However, permanent retention occurred only in males after DBP exposure on GD 16
      and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal
      weights; while exposure on only GD 16 and 17 caused a significant increase in the
      weights of the testes due to edema. In this study, epididymal and testicular
      malformations were most prevalent after exposure to DBP on any gestational day.
      Epididymal malformations, characterized by agenesis of various regions and small
      or flaccid testes were significantly increased in DBP-exposed males only on GD 16
      and 17. CONCLUSIONS: These findings suggest that 2-day DBP exposure is highly
      detrimental to the developing reproductive tract of the male fetus and the
      critical window for abnormal development is GD 16-18.

PMID- 15954089
TI  - Recombinant shark natural antibodies to thyroglobulin.
AB  - As cartilaginous fish are the vertebrates most distal from man to produce
      antibodies, fundamental information regarding conservation and variation of the
      antigen binding site should be gained by comparing the properties of antibodies
      directed against the same antigen from the two species. Since monoclonal cell
      lines cannot be generated using shark B cells, we isolated antigen binding
      recombinant single chain Fv antibodies (scFv) comprising of the complete variable
      regions from shark light and heavy chains. Thyroglobulin was used as the
      selecting antigen as both sharks and humans express natural antibodies to
      mammalian thyroglobulin in the absence of purposeful immunization. We report that
      recombinant sandbar shark (Carcharhinus plumbeus) scFvs that bind bovine
      thyroglobulin consist of heavy chain variable regions (VH) homologous to those of
      the human VHIII subset and light chain variable regions (VL) homologous to those
      of the human Vlambda6 subgroup. The homology within the frameworks is sufficient
      to enable the building of three-dimensional models of the shark VH/VL structure
      using established human structures as templates. In natural antibodies of both
      species, the major variability lies in the third complementarity determining
      region (CDR3) of both VH and VL.

PMID- 15954090
TI  - Viral and host factors in early hepatitis C virus infection.
AB  - Since 1980, the Transfusion-transmitted Viruses Study (TTVS) (1974-1980) has
      continued to maintain its computerized database and stored sera to enable ongoing
      study of new transfusion events since the 1970s. Most recently, we have used this
      resource to study parameters of acute hepatitis C virus (HCV) infection among 94
      donor-recipient pairs in which there was transmission. In addition, frequent
      recipient observations permitted further characterization of the early phase of
      the infection's course. Donor RNA load ranged from 3.7 to 3,160,000 IU/mL. Onset
      of recipient viremia was judged from a total of 67 sera collected during the 4th
      through 8th days posttransfusion; only 2 of the 67 sera were still RNA
      nonreactive by that time. The recipients' latent periods to an alanine
      aminotransferase (ALT) elevation of > or =90 IU/L ranged from 6 to 112 days
      (median, 46 days) and was shorter with higher donor RNA levels. Descriptors of
      the recipient's illness showed several strongly positive and negative
      correlations. The latent period tended to be shorter in the 37% of cases that
      were clinically overt. Attributes of donors with genotypes 1 and non-1 and
      subtypes 1a and 1b did not differ significantly. Recipients with genotype 1
      strains had shorter latent intervals than non-1 strains. On multivariate
      analysis, latent period was significantly associated (negatively) only with the
      highest ALT level during the first 120 days of follow-up (P = .014). In
      conclusion, host factors are more important determinants of acute HCV infection
      dynamics than virus-associated factors.

PMID- 15954091
TI  - Interview with Dr Evelyn Fox Keller [Interview by Marleen Wynants].

PMID- 15954092
TI  - Chromosome chains and platypus sex: kinky connections.
AB  - Mammal sex determination depends on an XY chromosome system, a gene for testis
      development and a means of activating the X chromosome. The duckbill platypus
      challenges these dogmas.(1,2) Gutzner et al.(1) find no recognizable SRY sequence
      and question whether the mammalian X was even the original sex chromosome in the
      platypus. Instead they suggest that the original platypus sex chromosomes were
      derived from the ZW chromosome system of birds and reptiles. Unraveling the
      puzzles of sex determination and dosage compensation in the platypus has been
      complicated by the fact that it has a surplus of sex chromosomes. Rather than a
      single X and Y chromosome, the male platypus has five Xs and five Ys.

PMID- 15954093
TI  - Beta1 integrins and neural stem cells: making sense of the extracellular
      environment.
AB  - Neural Stem Cells (NSC) are present in the developing and adult CNS. In both the
      embryonic and adult neurogenic regions, beta1 integrins may act as sensors for
      the changing extracellular matrix. Here we highlight the integrative functions
      that beta1 integrins may play in the "niche" by regulating NSC growth factor
      responsiveness in a timely and spatially controlled manner. beta1 integrins may
      provide NSC with the capacity to react to a dynamic "niche", and to respond
      adequately by either remaining as stem cells or by differentiating and migrating
      away to shape the developing cortex.

PMID- 15954094
TI  - Cartilage formation in growth plate and arteries: from physiology to pathology.
AB  - Vascular calcifications are the consequence of several pathological conditions
      such as atherosclerosis, diabetes, hypercholesterolemia and chronic renal
      insufficiency. They are associated with risks of amputation, ischemic heart
      disease, stroke and increased mortality. A growing body of evidence indicates
      that vascular smooth muscle cells (VSMCs) undergo chondrogenic commitment
      eventually leading to vascular calcification, by mechanisms similar to those
      governing ossification in the cartilage growth plate. Our knowledge of the
      formation of cartilage growth plate can therefore help us to understand why and
      how arteries calcify and, consequently, develop new therapeutic strategies.
      Reciprocally, thorough consideration of the events leading to ectopic chondrocyte
      differentiation appears crucial to further increase our understanding of growth
      plate formation. In this context, we will review the effects of known or
      suspected factors that promote chondrogenic differentiation in growth plate and
      arteries.

PMID- 15954095
TI  - Proliferation of dinoflagellates: blooming or bleaching.
AB  - The dinoflagellates, a diverse sister group of the malaria parasites, are the
      major agents causing harmful algal blooms and are also the symbiotic algae of
      corals. Dinoflagellate nuclei differ significantly from other eukaryotic nuclei
      by having extranuclear spindles, no nucleosomes and enormous genomes in liquid
      crystal states. These cytological characteristics were related to the acquisition
      of prokaryotic genes during evolution (hence Mesokaryotes), which may also
      account for the biochemical diversity and the relatively slow growth rates of
      dinoflagellates. The fact that the proliferation of many dinoflagellates is
      sensitive to turbulence may be due to the physiological requirements of the
      genome's liquid crystal states. Mechanical stress and anti-microtubule drugs
      induce cell cycle arrest mainly in G1, implicating a role for the permanent
      cortical microtubular cytoskeleton in mechanotransduction. The cell cycles of
      photosynthetic dinoflagellates are also gated by the circadian rhythm, with cell
      division occurring mainly at the end of the dark phase. Cell growth and the
      biosynthesis of many toxins occur during the light phase, corresponding to G1 in
      the cell cycle. The dinoflagellates also embody several options for coupling cell
      cycle progression to cell growth, enabling them to make the best use of available
      resources and possibly preparing them for a symbiotic existence.

PMID- 15954096
TI  - What tangled web: barriers to rampant horizontal gene transfer.
AB  - Dawkins in his The Selfish Gene(1) quite aptly applies the term "selfish" to
      parasitic repetitive DNA sequences endemic to eukaryotic genomes, especially
      vertebrates. Doolittle and Sapienza(2) as well as Orgel and Crick(3) enlivened
      this notion of selfish DNA with the identification of such repetitive sequences
      as remnants of mobile elements such as transposons. In addition, Orgel and
      Crick(3) associated parasitic DNA with a potential to outgrow their host genomes
      by propagating both vertically via conventional genome replication as well as
      infectiously by horizontal gene transfer (HGT) to other genomes. Still later,
      Doolittle(4) speculated that unchecked HGT between unrelated genomes so
      complicates phylogeny that the conventional representation of a tree of life
      would have to be replaced by a thicket or a web of life.(4) In contrast,
      considerable data now show that reconstructions based on whole genome sequences
      are consistent with the conventional "tree of life".(5-10) Here, we identify
      natural barriers that protect modern genome populations from the inroads of
      rampant HGT.

PMID- 15954097
TI  - Hox and wings.
AB  - In many bilaterian phyla, appendages are morphological traits that characterise
      the identity of the various body parts. In pterygote insects, wings are dorsal
      appendages on the thorax. The famous "bithorax" fly created by Ed Lewis is the
      emblematic example of the role of Hox genes.1 Now, Tomoyasu et al.,2 using
      classical genetics, transgenesis and RNAi, have examined the function of thoracic
      Hox genes in the beetle Tribolium castaneum. Beetles have rigid elytra in place
      of the first pair of wings. Instead of the expected transformation of the elytron
      into a wing, loss of Hox genes' function leads to the homeotic transformation of
      the second pair of dorsal appendages, the wings, into elytra. This has important
      consequences for the way that we see the role of Hox genes in development and
      evolution.

PMID- 15954098
TI  - Association by guilt: identification of DLX5 as a target for MeCP2 provides a
      molecular link between genomic imprinting and Rett syndrome.
AB  - Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting
      almost exclusively girls. Although mutations in methyl-CpG-binding protein
      (MeCP2) are known to be associated with RTT, gene expression patterns are not
      significantly altered in MeCP2-deficient cells. A recent study1 identified MeCP2
      mediated histone modification and formation of a higher-order chromatin loop
      structure specifically associated with silent chromatin at the Dlx5-Dlx6 locus in
      normal cells, and its absence thereof in RTT patients. This altered expression of
      Dlx5 through loss of silent chromatin loop formation provides a molecular
      mechanism underlying RTT and proposes a novel role for MeCP2 in chromatin
      organization and imprinting.

PMID- 15954099
TI  - Chromosome ends: different sequences may provide conserved functions.
AB  - The structures of specific chromosome regions, centromeres and telomeres, present
      a number of puzzles. As functions performed by these regions are ubiquitous and
      essential, their DNA, proteins and chromatin structure are expected to be
      conserved. Recent studies of centromeric DNA from human, Drosophila and plant
      species have demonstrated that a hidden universal centromere-specific sequence is
      highly unlikely. The DNA of telomeres is more conserved consisting of a tandemly
      repeated 6-8 bp Arabidopsis-like sequence in a majority of organisms as diverse
      as protozoan, fungi, mammals and plants. However, there are alternatives to short
      DNA repeats at the ends of chromosomes and for telomere elongation by telomerase.
      Here we focus on the similarities and diversity that exist among the structural
      elements, DNA sequences and proteins, that make up terminal domains (telomeres
      and subtelomeres), and how organisms use these in different ways to fulfil the
      functions of end-replication and end-protection.

PMID- 15954100
TI  - Multiple but dissectible functions of FEN-1 nucleases in nucleic acid processing,
      genome stability and diseases.
AB  - Flap EndoNuclease-1 (FEN-1) is a multifunctional and structure-specific nuclease
      involved in nucleic acid processing pathways. It plays a critical role in
      maintaining human genome stability through RNA primer removal, long-patch base
      excision repair and resolution of dinucleotide and trinucleotide repeat secondary
      structures. In addition to its flap endonuclease (FEN) and nick exonuclease (EXO)
      activities, a new gap endonuclease (GEN) activity has been characterized. This
      activity may be important in apoptotic DNA fragmentation and in resolving stalled
      DNA replication forks. The multiple functions of FEN-1 are regulated via several
      means, including formation of complexes with different protein partners, nuclear
      localization in response to cell cycle or DNA damage and post-translational
      modifications. Its functional deficiency is predicted to cause genetic diseases,
      including Huntington's disease, myotonic dystrophy and cancers. This review
      summarizes the knowledge gained through efforts in the past decade to define its
      structural elements for specific activities and possible pathological
      consequences of altered functions of this multirole player.

PMID- 15954101
TI  - Triggering TGFbeta and notch signalling cross-talk.

PMID- 15954102
TI  - Novel mutations in type 2 Gaucher disease in Chinese and their functional
      characterization by heterologous expression.
AB  - We investigated 10 unrelated Chinese patients with type 2 Gaucher disease and
      performed ex vivo expression for the novel mutations to characterize their
      functional defects. These patients were diagnosed by enzymatic assays and
      clinicopathologic features over the past five years in a national centre in
      China. Genomic DNA was sequenced by a two-stage PCR approach for mutations in the
      functional GBA gene. Novel mutations were expressed with baculovirus-transfected
      Sf21 cells. Six novel mutations were found (in traditional nomenclature): P122L,
      Y363C, N382K, L383R, L385P, and M416V. Review of reported mutations indicated
      clustering of type 2 mutations in three regions of the GBA gene. Expression of
      novel mutations revealed that the enzyme defect could arise from one of two
      mechanisms: loss of catalytic activity (Y363C and M416V) or enzyme instability
      (P122L and N382K).

PMID- 15954103
TI  - Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome.
AB  - This study summarizes 47 novel mutations identified during routine molecular
      diagnostics for Alport syndrome. We detected 34 in COL4A5, the gene responsible
      for X-linked Alport syndrome, and 13 in COL4A3 and COL4A4, the genes responsible
      for autosomal recessive Alport syndrome. A high detection rate of 90% was
      achieved among patients with typical clinical symptoms and a characteristic
      family history in both X-linked and autosomal recessive forms, and it can be
      assumed that most relevant mutations have been identified. In numerous positively
      tested patients, genetic variations which are unknown were detected.

PMID- 15954104
TI  - Mutation analysis of the GJB2 (connexin 26) gene in Egypt.
AB  - Fifty to eighty percent of autosomal recessive deafness is due to mutations in
      the GJB2 gene encoding connexin 26. Among Caucasians, the c.35delG mutation in
      this gene accounts for up to 30 to 70% of all cases with early childhood
      deafness. In this study, we present the analysis of the GJB2 gene in 159
      Egyptians from 111 families with non-syndromic mild to profound hearing
      impairment. An additional family with Vohwinkel syndrome, a combination of
      hearing impairment and palmoplantar keratoderma with constriction of the digits,
      was also included. We used direct sequencing analysis to detect all possible
      coding GJB2 variants in this population. The presence of the g.1777179_2085947del
      mutation (hereafter called del(GJB6-D13S1830)) was also investigated as it was
      shown to be the second most common mutation causing non-syndromic prelingual
      hearing impairment in Spain. Sequencing analysis of one randomly chosen
      individual per family revealed that the c.35delG mutation was present in 24 out
      of 222 chromosomes (10.8%), making it the most frequent mutation in the GJB2 gene
      in Egypt. Five other mutations were already described previously [p.Thr8Met,
      p.Val37Ile, p.Val153Ile, c.333_334delAA, c.1-3172G>A (commonly designated as
      IVS1+1G>A)]. This study also revealed three other novel gene variants resulting
      in amino acid substitutions (p.Phe142del, p.Asp117His, p.Ala148Pro). In contrast
      with most populations, the del(GJB6-D13S1830) mutation upstream of the GJB2 gene
      was not present in this Egyptian population. A dominant mutation at a highly
      conserved residue, p.Gly130Val, was found in the family with Vohwinkel syndrome.

PMID- 15954106
TI  - Transcoronary transplantation of autologous mesenchymal stem cells and
      endothelial progenitors into infarcted human myocardium.
AB  - The aim of the study was to investigate whether a combination of mesenchymal stem
      cells (MSCs) capable of differentiating into cardiac myocytes and endothelial
      progenitors (EPCs) that mainly promote neoangiogenesis might be able to
      facilitate tissue repair in myocardial scars. Previous studies have shown that
      intracoronary transplantation of autologous bone marrow stem cells results in
      improvement of contractility in infracted areas of human myocardium. Eleven
      patients with an anteroseptal myocardial infarction (MI) underwent transcoronary
      transplantation of bone marrow-derived MSCs and EPCs to the infarcted area
      through the left anterior descending artery. Eleven age- and sex-matched patients
      served as controls. Wall motion score index was significantly lower at follow-up
      in the transplantation (P = 0.04) but not in the control group. On stress
      echocardiography, there was improvement of myocardial contractility in one or
      more previously nonviable myocardial segments in 5 out of 11 patients (all with
      recent infarctions) and in none of the controls (P = 0.01). Restoration of uptake
      of Tc(99m) sestamibi in one or more previously nonviable myocardial scars was
      seen in 6 out of 11 patients subjected to transplantation and in none of the
      controls (P = 0.02). Cell transplantation was an independent predictor of
      improvement of nonviable tissue. Intracoronary transplantation of MSCs and EPCs
      is feasible, safe, and may contribute to regional regeneration of myocardial
      tissue early or late following MI.

PMID- 15954109
TI  - Autoimmune hepatitis: effect of symptoms and cirrhosis on natural history and
      outcome.
AB  - Although the natural history of autoimmune hepatitis (AIH) has been
      characterized, little is known about patients who present asymptomatically.
      Consequently, whether they require immunosuppressive therapy with its associated
      complications is unclear. To compare the natural history of asymptomatic AIH with
      symptomatic AIH, a large cohort of patients from a single center was examined.
      All patients with a clinical diagnosis of AIH were reassessed using the revised
      criteria of the International Autoimmune Hepatitis Group. Liver histology,
      response to therapy, and survival were assessed. Patients asymptomatic at
      presentation (n = 31) had lower serum aminotransferase, bilirubin, and
      immunoglobulin G (IgG) values at baseline. Half of the asymptomatic patients
      received no therapy, and their survival was no different from that of the total
      cohort. Ten-year survival was 80.0% (62.5%-97.5%) in the asymptomatic group and
      83.8% (75.1%-92.6%) in the symptomatic patients (P = NS). Survival to liver
      related endpoints at 10 years was similar in both groups: 89.5% (75.7%-100%)
      asymptomatic and 83.8% (75.1%-92.6%) symptomatic patients (P = NS). Patients with
      cirrhosis at baseline had poorer 10-year survival (61.9% [CI 44.9%-78.9%]) than
      those without cirrhosis at presentation (94.0% [CI 87.4%-100%]) (P = .003)
      regardless of whether they presented with symptoms or whether they received
      immunosuppressive therapy. In conclusion, patients with AIH who are asymptomatic
      at presentation have a good prognosis and may not require immunosuppressive
      therapy. Cirrhosis on initial liver biopsy portends a poor prognosis in all
      patients with AIH.

PMID- 15954111
TI  - Identification of nine novel DHCR7 missense mutations in patients with Smith
      Lemli-Opitz syndrome (SLOS).
AB  - Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive, multiple congenital
      anomaly syndrome caused by deficiency of 7-dehydrocholesterol reductase (DHCR7),
      which catalyzes the last step of endogenous cholesterol synthesis. Surveys of
      SLOS patients have identified more than one hundred point mutations of the DHCR7
      gene, most of which are missense mutations. Here, we report the identification of
      nine novel missense mutations of the DHCR7 gene.

PMID- 15954110
TI  - Spondylo-mega-epiphyseal dysplasia with prominent upper limb mesomelia, punctate
      calcifications, and deafness.
AB  - We report on a previously undescribed form of skeletal dysplasia with rhizomelic,
      acromelic, and prominent mesomelic shortening, distal ulnar epiphyseal and pubic
      punctate calcifications (stippling), mega-epiphyses, platyspondyly, anterior
      beaking of the vertebrae, and sensorineural hearing loss. We compare this case to
      the other reported forms of skeletal dysplasias, particularly the mesomelic,
      acromesomelic, and mega-epiphyseal disorders.

PMID- 15954112
TI  - Sarcoglycanopathies and the risk of undetected deletion alleles in diagnosis.
AB  - We have designed Multiplex Amplifiable Probe Hybridization (MAPH) probes for 28
      exons of the sarcoglycan genes SGCA, SGCB, SGCG, and SGCD. The set was used to
      screen DNA from limb-girdle muscular dystrophy (LGMD) patients for the presence
      of pathogenic deletion or duplication mutations. An unexpected heterozygous
      deletion of SGCG exon 7 was detected in a patient from a consanguineous family in
      which a known c.525delT mutation segregates. The exon 7 deletion was inherited
      from the father, who was part of the consanguineous c.525delT branch of the
      family but who did not carry the c.525delT mutation. A similar, homozygous
      deletion had been identified in two unrelated LGMD patients from southern Italy.
      The deletion breakpoints were mapped, isolated, and sequenced, and were identical
      in all cases. Haplotype analysis showed the same alleles segregating with the
      mutation in all three patients, suggesting a common ancestor. Exonic deletions in
      sarcoglycanopathies appear to be rare events. However, we recommend screening for
      exonic deletions/duplications in patients where a mutation has not been
      identified in both alleles, as well as in seemingly homozygous cases where
      segregation of the mutations can not be confirmed in the parents.

PMID- 15954113
TI  - Helium-neon laser in viability of random skin flap in rats.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the role of
      helium-neon (He-Ne) laser random skin flap viability in rats. STUDY
      DESIGN/MATERIALS AND METHODS: Experimentally controlled randomized study. Forty
      eight Wistar-EPM rats were used, weighed, and divided into 4 groups with 12 rats
      each. The random skin flap was performed measuring 10 x 4 cm, with a plastic
      sheet interposed between the flap and the donor site. The Group 1 (control)
      underwent sham irradiation with He-Ne laser. The Group 2 was submitted to laser
      irradiation, using the punctual contact technique on the skin flap surface. The
      Group 3 was submitted to laser irradiation surrounding the skin flap, and the
      Group 4 was submitted to laser irradiation both on the skin flap surface and
      around it. The experimental groups were submitted to He-Ne laser irradiation with
      3 J/cm(2) energy density immediately after the surgery and for the four
      subsequent days. The percentage of necrotic area of the four groups was
      calculated at the 7th post-operative day, through a paper-template method.
      RESULTS: Group 1 reached an average necrotic area of 48.86%; Group 2, 38.67%;
      Group 3, 35.34%; and Group 4, 22.61%. After the statistic analysis, results
      showed that all experimental groups reached statistically significant values when
      compared to the control group, and Group 4 was the best one, when compared to all
      groups of this study (P<0.001). CONCLUSION: The He-Ne laser irradiation was
      efficient to increase random skin flap viability in rats.

PMID- 15954114
TI  - Effect of the 1,450 nm diode non-ablative laser on collagen expression in an
      artificial skin model.
AB  - BACKGROUND AND OBJECTIVE: The 1,450-nm Smoothbeam Laser is a diode laser equipped
      with a cryogen cooling spray. Primary objectives were to evaluate the effects of
      this non-ablative laser on Apligraf (bioengineered skin-substitute) and to
      document its use as a model for non-ablative procedures. We also measured the
      effects of laser fluence levels on collagen and elastin expression. STUDY
      DESIGN/MATERIALS AND METHODS: Three sheets of Apligraf were used for this study.
      Each received six separate laser applications at 4J, 6J, 8J, 10 J, 12J, and 14J.
      The sheets were then incubated with 10% CO(2) at 37 degrees C and samples were
      collected and analyzed 3 days later, using RT-PCR and immunofluorescent staining.
      RESULTS: Collagen III expressions significantly increased in both mRNA and
      protein levels at approximately 12 J. CONCLUSIONS: There appears to be a
      threshold effect where there is very little increased collagen III mRNA and
      protein expression until the laser fluence reaches around 12J.

PMID- 15954115
TI  - Cytologic and DNA-cytometric follow-up of oral leukoplakia after CO2- and Er:YAG
      laser assisted ablation: a pilot study.
AB  - BACKGROUND AND OBJECTIVES: The aim of the present pilot study was to determine
      therapeutic responses to Er:YAG- and CO(2)-laser ablation in patients with oral
      leukoplakia as evaluated by means of exfoliative cytology (EC) and DNA-image
      cytometry (DNA-I). STUDY DESIGN/MATERIALS AND METHODS: Ten patients exhibiting a
      total of 16 lesions affecting a variety of intraoral sites were randomly treated
      with either (1) an Er:YAG laser (300 mJ/pulse, 10 Hz, defocused mode) (ERL), or
      (2) an CO(2) laser (4-6 W, 20-50 Hz, focused mode) (CO). Brush (B) and incisional
      (I) biopsies were obtained from the respective lesions immediately before
      treatment (B, I) as well as 24-96 weeks postoperatively (B). In cases, in which
      EC revealed suspicious cells, nuclear DNA-contents were measured using a TV image
      analysis system. RESULTS: Both treatment approaches resulted in a complete (C) or
      partial (P) remission of all investigated lesions. In particular, ERL exhibited
      C(3), P(5), and CO C(5), P(3). However, in the CO group, two of eight lesions
      showed a recurrence 32-48 weeks following treatment. Among all investigated
      lesions, both histological and EC/DNA-I diagnosis revealed no sign of malignancy
      or dysplasia before or following laser assisted ablation. CONCLUSIONS: Within the
      limits of the present study, it may be concluded that both treatment approaches
      seem to have limitations to achieve predictable eradication of oral leukoplakia.

PMID- 15954116
TI  - Effect of kynurenine 3-hydroxylase inhibition on the dyskinetic and
      antiparkinsonian responses to levodopa in Parkinsonian monkeys.
AB  - Homeostatic interactions between dopamine and glutamate are central to the normal
      physiology of the basal ganglia. This relationship is altered in Parkinsonism and
      in levodopa-induced dyskinesias (LID), resulting in an upregulation of
      corticostriatal glutamatergic function. Kynurenic acid (KYNA), a tryptophan
      metabolite with antagonist activity at ionotropic glutamate receptors and the
      capability to inhibit glutamate release presynaptically, might therefore be of
      therapeutic value in LID. To evaluate this hypothesis, we used a pharmacological
      tool, the kynurenine 3-hydroxylase inhibitor Ro 61-8048, which raises KYNA levels
      acutely. Ro 61-8048 was tested in MPTP cynomolgus monkeys with a stable
      parkinsonian syndrome and reproducible dyskinesias after each dose of levodopa.
      Serum and CSF concentrations of KYNA and its precursor kynurenine increased dose
      dependently after Ro 61-8048 administration, alone or in combination with
      levodopa. Coadministration of Ro 61-8048 with levodopa produced a moderate but
      significant reduction in the severity of dyskinesias while maintaining the motor
      benefit. These results suggest that elevation of KYNA levels through inhibition
      of kynurenine 3-hydroxylase constitutes a promising novel approach for managing
      LID in Parkinson's disease.

PMID- 15954117
TI  - Systematic review of the literature of low-level laser therapy (LLLT) in the
      management of neck pain.
AB  - BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) is widely used in the
      treatment of musculoskeletal pain. However, there is controversy over its true
      efficacy. We aimed to determine the efficacy of LLLT in the treatment of neck
      pain through systematically reviewing the literature. STUDY DESIGN/MATERIALS AND
      METHODS: A search of computerized bibliographic databases covering medicine,
      physiotherapy, allied health, complementary medicine, and biological sciences was
      undertaken undertaken from date of inception until February 2004 for randomized
      controlled trials of LLLT for neck pain. A comprehensive list of search terms was
      applied and explicit inclusion criteria were developed a priori. Twenty studies
      were identified, five of which met the inclusion criteria. RESULTS: Significant
      positive effects were reported in four of five trials in which infrared
      wavelengths (lambda = 780, 810-830, 904, 1,064 nm) were used. Heterogeneity in
      outcome measures, results reporting, doses, and laser parameters precluded formal
      meta-analysis. Effect sizes could be calculated for only two of the studies.
      CONCLUSIONS: This review provides limited evidence from one RCT for the use of
      infrared laser for the treatment of acute neck pain (n = 71) and chronic neck
      pain from four RCTs (n = 202). Larger studies are required to confirm the
      positive findings and determine the most effective laser parameters, sites and
      modes of application.

PMID- 15954118
TI  - Characterization of small nodules in cirrhosis by assessment of vascularity: the
      problem of hypovascular hepatocellular carcinoma.
AB  - In a prospective study, we examined the impact of arterial hypervascularity, as
      established by the European Association for the Study of the Liver (EASL)
      recommendations, as a criterion for characterizing small (1-3 cm) nodules in
      cirrhosis. A total of 72 nodules (1-2 cm, n = 41; 2.1-3 cm, n = 31) detected by
      ultrasonography in 59 patients with cirrhosis were included in the study. When
      coincidental arterial hypervascularity was detected at contrast perfusional
      ultrasonography and helical computed tomography, the lesion was considered to be
      hepatocellular carcinoma (HCC) according to EASL criteria. When one or both
      techniques showed negative results, ultrasound-guided biopsy was performed. In
      cases with negative results for malignancy or high-grade dysplasia, biopsy was
      repeated when an increase in size was detected at the 3-month follow-up
      examination. Coincidental hypervascularity was found in 44 of 72 nodules (61%;
      44% of 1-2-cm nodules and 84% of 2-3-cm nodules). Fourteen nodules (19.4%) had
      negative results with both techniques (hypovascular nodules). Biopsy showed HCC
      in 5 hypovascular nodules and in 11 of 14 nodules with hypervascularity using
      only one technique. All nodules larger than 2 cm finally resulted to be HCC. Not
      satisfying the EASL imaging criteria for diagnosis were 38% of HCCs 1 to 2 cm
      (17% hypovascular) and 16% of those 2 to 3 cm (none hypovascular). In conclusion,
      the noninvasive EASL criteria for diagnosis of HCC are satisfied in only 61% of
      small nodules in cirrhosis; thus, biopsy frequently is required in this setting.
      Relying on imaging techniques in nodules of 1 to 2 cm would miss the diagnosis of
      HCC in up to 38% of cases. Any nodule larger than 2 cm should be regarded as
      highly suspicious for HCC.

PMID- 15954119
TI  - Properties of acrylic bone cements formulated with Bis-GMA.
AB  - Experimental cement formulations were prepared by replacing part of the
      methylmethacrylate (MMA) liquid phase of a conventional surgical cement with an
      equivalent weight of 2,2-bis [4(2-hydroxy-3-methacryloxypropoxy) phenyl] propane
      (Bis-GMA), which is the reaction product of diglycidyl ether of bisphenol A and
      methacrylic acid. It was found that up to 50 wt % of the MMA could be replaced by
      Bis-GMA without reductions in flow characteristics of the precured polymers.
      Cements containing 20, 30, 40, and 50 wt % of Bis-GMA in the liquid component
      were prepared. Over this range of Bis-GMA wt %, it was found that, relative to
      the unmodified cement, the volumetric shrinkage (DV), the peak temperature
      reached during the polymerization reaction (Tp), and the flexural strength
      (obtained in three-point bend tests) were each significantly reduced, the
      flexural modulus (obtained in three-point bend tests) increased significantly,
      the compressive strength increased slightly, while there were no significant
      effects on any of the other properties determined, namely, degree of conversion
      of the monomer during the polymerization reaction and the glass transition
      temperature. The drops in D(V) and Tp indicate that cements whose liquid monomers
      are modified using Bis-GMA hold promise for use in anchoring total joint
      replacements. The increase in the crosslinking density with increasing amount of
      Bis-GMA renders the polymer matrix more brittle. This feature was considered
      responsible for the reduced flexural strength.

PMID- 15954120
TI  - ED50 study of femtosecond terawatt laser pulses on porcine skin.
AB  - BACKGROUND AND OBJECTIVES: Terawatt (TW) lasers have become commonplace since the
      development of the chirped-pulse amplification method using Ti:sapphire and
      Nd:glass laser rods. We have measured the minimum visible lesion (MVL) thresholds
      for porcine1The animals involved in this study were procured, maintained, and
      used in accordance with the Federal Animal Welfare Act and the "Guide for the
      Care and Use of Laboratory Animals" prepared by the Institute of Laboratory
      Animal Resources-National Research Council. Brooks City-Base, TX has been fully
      accredited by the Association for Assessment and Accreditation of Laboratory
      Animal Care, International (AAALAC) since 1967. (Yucatan mini-pig) skin using TW
      laser pulses. STUDY DESIGN/MATERIALS AND METHODS: Our system produced laser
      pulses at 810 nm and sub-50 femtoseconds. These 1-2 TW laser pulses created
      multiple self-focusing (SF) filaments during propagation and were directed on the
      flanks of mini-pigs under anesthesia. We measured the pulse energies necessary to
      determine the ED(50) skin damage thresholds. RESULTS: The MVL ED(50) threshold at
      1 hour was 8 mJ and increased to 21 mJ after 24 hours. Histological sections were
      obtained after 1-hour and 24-hour readings. CONCLUSIONS: The damage patterns on
      the skin indicated the number of filaments in the laser pulse. Many of the pulses
      produced only superficial damage that disappeared in 24 hours and that nearly
      three times the pulse energy was required to cause subdural or cellular damage.
      With further research, non-thermal tissue ablation using TW laser pulses could
      provide a viable alternative to current techniques of laser use in dermatology.

PMID- 15954121
TI  - Progressive microvascular injury in liver and colorectal liver metastases
      following laser induced focal hyperthermia therapy.
AB  - BACKGROUND AND OBJECTIVES: Focal hyperthermia by laser or radiofrequency is
      currently the preferred method for local ablation of liver tumors. The underlying
      mechanism of action of focal hyperthermia, in particular the relationship between
      the microvascular and tissue effect is uncertain and was investigated in a murine
      model. STUDY DESIGN/MATERIALS AND METHODS: Focal hyperthermia produced by a
      Neodymium-Yttrium-Aluminium-Garnet laser (wavelength 1,064 nm) was applied to the
      normal liver and colorectal cancer liver metastases in inbred male CBA strain
      mice at 2 W for 50 seconds (100 J). Tissue injury was assessed at 0, 24, 48, 72,
      120, and 168 hours following therapy by measurements of necrosis in tissue
      sections stained for nicotinamide adenine dinucleotide (NADH) diaphorase
      activity. Characteristics of microvascular injury were assessed at the various
      time points by scanning electron microscopy (SEM) of vascular resin casts, Laser
      Doppler flowmetry, and confocal in vivo microscopy. RESULTS: Focal hyperthermia
      produced progressive tissue and vascular injury. There was an initial reduction
      in blood flow and increased vascular permeability in the microcirculation of both
      tumor and liver tissue immediately following heat application as assessed by
      laser Doppler flowmetry and confocal in vivo microscopy, respectively. SEM of
      vascular casts showed heterogeneous regions of microvascular injury immediately
      following heat application. The extent of initial vascular disruption or
      occlusion on SEM of vascular resin casts (mean+/-SE) was significantly less than
      the tissue necrosis in liver (1.9+/-0.1 mm vs. 3.0 mm+/-0.2 mm P<0.001), but was
      equivalent to the tissue injury in tumor tissue (3.5 mm+/-0.2 mm vs. 3.6 mm+/-0.1
      mm P = 0.907). This was followed by a progressive increase in both microvascular
      and tissue injury in liver and tumor that peaked by 72 hours following treatment.
      The peak microvascular injury and tissue damage in liver (6.6 mm+/-0.2 and 6.3
      mm+/-0.2 mm, respectively) was significantly greater than the extent of
      microvascular and tissue damage in tumors (4.8 mm+/-0.2 mm and 4.5 mm+/-0.2 mm,
      respectively) (P<0.001). The progression of microvascular injury in liver and
      tumor at times preceded the tissue injury. CONCLUSION: Focal hyperthermia
      produces both progressive microvascular and tissue damage in liver and colorectal
      liver metastases. An increase in tissue injury following focal hyperthermia may
      be a direct result of progressive microvascular damage. Tumor vessels appear more
      susceptible to direct focal hyperthermia destruction than liver sinusoids. The
      liver sinusoids are however more susceptible to progressive damage or occlusion
      following the initial laser thermal stimulus.

PMID- 15954122
TI  - Time-resolved autofluorescence spectroscopy for classifying normal and
      premalignant oral tissues.
AB  - BACKGROUND AND OBJECTIVES: Time-resolved autofluorescence spectroscopy has been
      used for effectively distinguishing normal tissues from precancers and cancers in
      various organs. The aim of this study was to find out the possibility of using
      time-resolved autofluorescence spectroscopy to differentiate normal oral mucosa
      (NOM) from oral premalignant lesions including verrucous hyperplasia (VH),
      epithelial hyperplasia (EH), and epithelial dysplasia (ED). STUDY
      DESIGN/MATERIALS AND METHODS: Time-resolved autofluorescence spectra at 633 nm
      under 410-nm excitation were recorded for 15 VH, 9 EH, 14 ED, and 38 NOM samples.
      The two-component lifetimes of the obtained curves were calculated, and a
      Fisher's discriminant analysis (FDA) was employed for distinguishing these tissue
      samples. RESULTS: After two-component lifetimes for all samples being calculated,
      a two-dimensional scatter plot was developed, in which 76 oral tissue samples
      were separated into three groups by FDA. With a leave-one-out method, the FDA
      algorithm gave an accuracy rate of 93% for ED, of 75% for VH and EH, and of 100%
      for NOM samples. In addition, all oral premalignant lesions (including VH, EH,
      and ED) could be distinguished from NOM samples by this FDA algorithm.
      CONCLUSIONS: We conclude that time-resolved autofluorescence spectroscopy at 633
      nm under 410-nm excitation, based on two-component lifetime calculation and FDA,
      is a very sensitive technique for in vivo diagnosis of oral premalignant lesions.
      .

PMID- 15954123
TI  - Enhanced extrastriate visual response to bandpass spatial frequency filtered
      fearful faces: time course and topographic evoked-potentials mapping.
AB  - We compared electrical brain responses to fearful vs. neutral facial expressions
      in healthy volunteers while they performed an orthogonal gender decision task.
      Face stimuli either had a broadband spatial-frequency content, or were filtered
      to create either low spatial-frequency (LSF) or high spatial-frequency (HSF)
      faces, always overlapped with their complementary SF content in upside-down
      orientation to preserve the total stimulus energy. We tested the hypothesis that
      the coarse LSF content of faces might be responsible for an early modulation of
      event-related potentials (ERPs) to fearful expressions. Consistent with previous
      findings, we show that broadband images of fearful faces, relative to neutral
      faces, elicit a higher global field power of approximately 130 ms poststimulus
      onset, corresponding to an increased P1 component over lateral occipital
      electrodes, with neural sources located within the extrastriate visual cortex.
      Bandpass filtering of faces strongly affected the latency and amplitude of ERPs,
      with a suppression of the normal N170 response for both LSF and HSF faces,
      irrespective of expression. Critically, we found that LSF information from
      fearful faces, unlike HSF information, produced a right-lateralized enhancement
      of the lateral occipital P1, without any change in the scalp topography, relative
      to unfiltered (broadband) fearful faces. These results demonstrate that an early
      P1 response to fear expression depends on a visual pathway preferentially tuned
      to coarse-magnocellular inputs, and can persist unchanged even when the N170
      generators are disrupted by SF filtering.

PMID- 15954124
TI  - Microglia in health and disease.
AB  - Microglia, one of three glial cell types in the central nervous system (CNS),
      play an important role as resident immunocompetent and phagocytic cells in the
      CNS in the event of injury and disease. It was del Rio Hortega in 1927 who
      determined that microglia belong a distinct glial cell type apart from astrocytes
      and oligodendrocytes, and since 1970s there has been wide recognition that
      microglia are immune effectors in the CNS that respond to pathological conditions
      and participate in initiation and progression of neurological disorders including
      Alzheimer's disease, Parkinson's disease, multiple sclerosis, and acquired immune
      deficiency syndrome dementia complex by releasing potentially cytotoxic molecules
      such as proinflammatory cytokines, reactive oxygen intermediates, proteinases and
      complement proteins. There is also evidence to suggest that microglia are capable
      of secreting neurotrophic or neuron survival factors upon activation via
      inflammation or injury. It is thus timely to review current status of knowledge
      on biology and immunology of microglia, and consider new directions of
      investigation on microglia in health and disease.

PMID- 15954125
TI  - Task-dependent modulation of silent period duration in focal hand dystonia.
AB  - Focal hand dystonia (FHD) is a movement disorder that is also associated with
      impaired sensory function and sensorimotor integration. The aim of this study was
      to assess the modulation of inhibitory function in the motor cortex during the
      performance of four motor tasks (isometric pinch grip, writing, texture
      discrimination, and a phasic control task) in 8 FHD and 8 control subjects. The
      affected hands of the FHD subjects and the dominant hands of the control subjects
      were tested. Inhibitory function was assessed using transcranial magnetic
      stimulation to evoke a silent period in the ongoing electromyographic activity of
      the target muscle (first dorsal interosseous). There was no difference between
      FHD subjects and control subjects in silent period duration, which was
      significantly longer during the phasic texture discrimination and phasic control
      task than during the isometric pinch or writing. This finding suggests that the
      phasic nature of the task may increase cortical inhibitory function, rather than
      the sensory discrimination task itself. The accuracy of texture discrimination
      was significantly lower in FHD subjects than in control subjects. Sensory
      discrimination tasks do not appear to directly modulate the inhibitory processes
      responsible for the duration of the silent period.

PMID- 15954126
TI  - Meige syndrome and pallidal deep brain stimulation.
AB  - The cause of primary Meige syndrome is unknown, and although gender and age
      predilections are different from idiopathic torsion dystonia, most investigators
      consider Meige syndrome a variant of that disorder. Interest in the use of
      stereotactic brain surgery for refractory forms of dystonia is thus increasing.
      There is little experience with the use of deep brain stimulation (DBS) in focal
      dystonias, and reports of its use in Meige syndrome are very rare. We report on a
      case of Meige syndrome successfully treated with bilateral pallidal DBS.

PMID- 15954127
TI  - Interaction between blood lead concentration and delta-amino-levulinic acid
      dehydratase gene polymorphisms increases the odds of essential tremor.
AB  - Blood lead (BPb) concentrations are elevated in essential tremor (ET) cases. The
      delta-amino-levulinic acid dehydratase (ALAD) gene codes for ALAD, the principal
      enzyme involved in lead kinetics. Carriers of the ALAD-2 allele may be more
      susceptible to lead toxicity. The objective of this study was to test, using a
      case-control design, whether an interaction between BPb concentration and ALAD
      allele status increases the odds of ET. Mean log BPb concentration was
      significantly higher in 63 cases than 101 controls (0.47+/-0.26 vs. 0.35+/-0.25
      microg/dl). Eighteen (28.6%) cases vs. 17 (16.8%) controls had an ALAD-2 allele
      (OR=1.98; 95% CI=0.93--4.21). In an adjusted logistic regression analysis, the
      interaction term (ALAD allele status x log BPb concentration) was associated with
      increased odds for ET. In stratified analyses, log BPb concentration was not
      associated with odds of ET in individuals with two ALAD-1 alleles (OR=2.69; 95%
      CI=0.61--11.82), but in individuals with an ALAD-2 allele, BPb concentration was
      significantly associated with odds of ET (OR=80.29; 95% CI=3.08--2,096.36). There
      was an interaction between BPb concentration and ALAD allele status; the odds of
      ET were greatly elevated in individuals with both an ALAD-2 allele and an
      elevated BPb concentration. The presence of increased circulating BPb
      concentrations along with a greater potential for lead toxicity (ALAD-2 allele)
      could result in greater cerebellar damage, thereby increasing the risk of
      developing tremor.

PMID- 15954128
TI  - Frequency of movement disorders in an Ethiopian university practice.
AB  - There is little information on the frequency of movement disorders seen by
      physicians in the continent of Africa. We performed a medical record review of
      all patients seen in a university-based neurology clinic in Addis Ababa,
      Ethiopia, over 1 year to determine the frequency of movement disorders seen,
      disease characteristics, diagnostic evaluations, and treatment. A total of 15.1%
      of the neurological patients were seen for movement disorders. Of these, most
      were for parkinsonism (47.7%), followed by ataxia (16.5%), dystonia (8.3%),
      essential tremor (8.3%), chorea (7.3%), and miscellaneous (11.9%). Diagnostic
      evaluations were limited, but treatment was available, although expensive. In
      spite of the limitations, patients with movement disorders require and seek care
      in Ethiopia in proportions comparable to developed nations. This finding
      underlines the need for adequate training in movement disorders for physicians
      and neurologists in Africa.

PMID- 15954129
TI  - Three brothers with a very-late-onset writer's cramp.
AB  - Writer's cramp (WC) is a form of focal task-specific dystonia, which is brought
      on by writing. Although most cases are sporadic, a positive family history is
      present in 5% to 20% of cases. To date, WC has been reported in several families
      with primary torsion dystonia, including DYT7, a pure focal dystonia, and in the
      mixed dystonias, DYT1, DYT6, and DYT13. We describe a family of Bulgarian descent
      with three brothers presenting with a very-late-onset dystonic WC, compatible
      with linkage to chromosome 18p.

PMID- 15954130
TI  - Normalization of voice in spasmodic dysphonia during transient global amnesia.
AB  - We report on the case of a 69-year-old woman with Parkinson's disease and long
      standing history of spasmodic dysphonia that reversed during an episode of
      transient global amnesia (TGA). To our knowledge, this phenomenon has not been
      reported before. We suggest possible mechanisms by which the pathophysiology of
      dystonia could reverse during TGA.

PMID- 15954131
TI  - Heat-related morbidity in patients with orthostatic hypotension and primary
      autonomic failure.
AB  - We investigated the effects of high-external-temperature exposure on neurogenic
      orthostatic hypotension (OH). Thirty-one patients with autonomic failure (AF) and
      pharmacologically treated OH related to probable multiple-system atrophy (n=7),
      Parkinson's disease (n=10), pure autonomic failure (n=7), and diffuse Lewy body
      disease (n=7) and 26 parkinsonians without AF were included. Prevalence and
      severity of clinical events were studied during the August 2003 heat wave and the
      2004 summer. The prevalence of OH-related events was significantly higher in 2003
      [45.1 vs. 11.5%; P=0.0052; OR=6.31 (1.35--33.53)] and 2004 [42.3 vs. 12.0%;
      P=0.014; OR=5.40 (1.28--22.68)] in AF than in controls. The mean severity score
      for clinical events was significantly higher in AF than in controls during 2003
      heat wave (1.2+/-1.4 vs. 0.2+/-0.5) but similar in summer 2004 (0.7+/-1.0 vs.
      0.1+/-0.3). Severe events (unusual home care, assistance, or hospitalization)
      were only observed in AF patients. A nonstatistically significant higher
      prevalence of clinical events was observed in AF patients prescribed
      fludrocortisone (66.7%) by comparison to heptaminol (42.9%), midodrine (45.5%),
      or midodrine plus fludrocortisone (28.6%). This study shows that AF patients have
      a poor clinical outcome when exposed to high temperatures and that heat exposure
      is a risk factor for OH worsening.

PMID- 15954132
TI  - Management of the extrapyramidal syndrome in chronic acquired hepatocerebral
      degeneration (CAHD).

PMID- 15954133
TI  - Clinical characteristics in early Parkinson's disease in a central California
      population-based study.
AB  - There is considerable variation in the phenotypic appearance of individuals with
      idiopathic Parkinson's disease (PD), which may translate into differences in
      disease progression in addition to underlying disease etiology. In this
      publication, we report on the demographic and clinical characteristics of 162
      individuals diagnosed with clinically probable PD from January 1998 to June 2003
      who resided in predominantly rural communities in central California. The
      majority of the subjects were Caucasian, male, and between 60 and 79 years of
      age. The akinetic-rigid and tremor-dominant subtypes were more common than the
      mixed subtype. The majority of subjects displayed motor signs of rigidity
      (92.0%), bradykinesia (95.7%), and gait problems (87.0%), whereas less than half
      (43.3%) of the subjects displayed a tremor. Three fourths of patients received a
      Hoehn and Yahr Scale score of Stage 2 or higher. One third of the patients were
      treated with levodopa, and patients under 60 years of age were more likely to be
      treated with dopamine agonists. Within 3 years after first diagnosis, 13% of
      subjects showed some signs of depression and 17% of subjects met criteria for
      mild dementia. Among our subjects, 17.3% reported a family history of PD in first
      or second-degree relatives,15.4% a family history of essential tremor, and 14.2%
      of Alzheimer's disease. This study represents the most extensive phenotypic
      description of rural U.S. residents in the initial stages of PD who were
      recruited in a population-based manner; future follow-up may provide valuable
      information regarding the prognostic indication of these symptoms/signs and
      improve our understanding of the underlying etiology of PD.

PMID- 15954134
TI  - Efficacy and safety of repeated doses of botulinum toxin type B in type A
      resistant and responsive cervical dystonia.
AB  - Efficacy of botulinum toxin type B (BoNT B) for the treatment of type A-resistant
      (AR) and non-A-resistant (NAR) cervical dystonia (CD) has been demonstrated in
      several single injection studies. There is little data available on long-term
      therapy with repeated injection sessions and it is unknown if AR and NAR patients
      respond in a similar manner over time. To evaluate the long-term efficacy and
      safety of BoNT B in AR and NAR CD patients, we carried out a prospective, open
      label study examining 10 repeated dosing sessions of BoNT B in 34 patients with
      CD (15 AR and 19 NAR). Dosing was started at 10,000 units and could be increased
      to 25,000. Assessments included the Toronto Western Spasmodic Torticollis Rating
      Scale (TWSTRS) and a patient global assessment at each baseline (injection) and
      Week 4 (peak effect) visit. Change in TWSTRS total was the primary efficacy end
      point. Data was analyzed using repeated-measures analysis of variance. BoNT B
      therapy resulted in an overall significant improvement of CD (P<0.001) and
      improvement was seen in all 10 individual sessions (2.5 years). The magnitude of
      response decayed over time (P<0.001). There was no difference between AR and NAR
      patients with regard to dose, treatment effect, or decay in response. The AR
      group perceived (patient global) treatment as being less effective (P=0.047). Dry
      mouth frequency decreased with each session despite increasing doses whereas flu
      like syndrome and weakness increased. BoNT B therapy provides long-term benefit
      for CD patients but the magnitude of response diminishes over time. The cause of
      this decay is probably multifactorial. AR and NAR CD patients respond in a
      similar fashion.

PMID- 15954135
TI  - Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa
      induced dyskinesias in Parkinson's disease.
AB  - We evaluated the tolerability and preliminary efficacy of levetiracetam (LEV;
      Keppra) in reducing levodopa-induced dyskinesias in Parkinson's disease (PD) in
      an open-label pilot study. Nine PD patients who were experiencing peak-dose
      dyskinesias for at least 25% of the awake day and were at least moderately
      disabling were treated with LEV in doses up to 3,000 mg for up to 60 days. The
      primary outcome measure was the percent of the awake day that patients spent on
      without dyskinesia or with nontroublesome dyskinesia (good on time). The mean
      dose of LEV at endpoint was 625+/-277 mg/day. LEV significantly improved percent
      of the awake day on without dyskinesia or with nontroublesome dyskinesia at
      endpoint compared to baseline (43% +/- 12% vs. 61% +/- 17%; P=0.02). Percent on
      time with troublesome dyskinesia decreased from 23% +/- 10% at baseline to 11% +/
      6% at endpoint, although not significantly. There was no significant increase in
      off time from baseline to endpoint. There was a 56% dropout rate, mostly due to
      somnolence. In PD patients who experienced peak-dose dyskinesia for at least 25%
      of the awake day, LEV significantly improved on time without dyskinesia or with
      nontroublesome dyskinesia.

PMID- 15954136
TI  - Parkinsonism and nigrostriatal dysfunction are associated with spinocerebellar
      ataxia type 6 (SCA6).
AB  - SCA6 is a slowly progressive, late-onset cerebellar ataxia due to a trinucleotide
      expansion in the CACNA1A gene. We describe two unrelated cases that presented
      with Parkinsonism and cerebellar ataxia. One case was L-dopa-responsive with a
      pattern of (18)F-dopa uptake similar to Parkinson's disease, and the second case
      was not L-dopa-responsive and had an atypical pattern of nigrostriatal
      dysfunction. We suggest that SCA6, in common with SCA2 and SCA3, may be
      associated with Parkinsonism attributable to nigral loss and dopaminergic
      dysfunction. Moreover, isolated cases may be confused with multiple system
      atrophy.

PMID- 15954137
TI  - Antidepressant studies in Parkinson's disease: a review and meta-analysis.
AB  - The objective of this study was to determine effect sizes for both antidepressant
      treatment and placebo for depression in Parkinson's disease (PD), and to compare
      the findings with those reported in elderly depressed patients without PD. Recent
      reviews have concluded that there is little empiric evidence to support the use
      of antidepressants in PD; however, available data has not been analyzed to
      determine the effect size for antidepressant treatment in PD depression. A
      literature review identified antidepressant studies in PD. Suitable studies were
      analyzed using meta-analytic techniques, and effect sizes were compared with
      those from antidepressant studies in elderly patients without PD. Large effect
      sizes were found for both active treatment and placebo in PD, but there was no
      difference between the two groups. In contrast, active treatment was superior to
      placebo in depressed elderly patients without PD. In PD, increasing age and a
      diagnosis of major depression were associated with better treatment response.
      Results also suggest that newer antidepressants are well tolerated in PD. Despite
      the high prevalence of depression and antidepressant use in PD, controlled
      treatment research has been almost nonexistent. Meta-analysis results suggest a
      large but nonspecific effect for depression treatment in PD. In addition, PD
      patients may benefit less from antidepressant treatment, particularly selective
      serotonin reuptake inhibitors, than do elderly patients without PD.

PMID- 15954138
TI  - Visual evoked potentials recovered from fMRI scan periods.
AB  - Simultaneous electroencephalography (EEG) and functional magnetic resonance
      imaging (fMRI) may allow functional imaging of the brain at high temporal and
      spatial resolution. Artifacts generated in the EEG signal during MR acquisition,
      however, continue to pose a major challenge. Due to these artifacts, an
      interleaved modus has often been used for "evoked potential" experiments, i.e.,
      only EEG signals recorded between MRI scan periods were assessed. An obvious
      disadvantage of this approach is the loss of a portion of the EEG information,
      which might be relevant for the specific scientific issue. In this study,
      continuous, simultaneous EEG-fMRI measurements were carried out. Visual evoked
      potentials (VEPs) could be reconstructed reliably from periods during MR scanning
      and in between successive scans. No significant differences between both VEPs
      were detected. This indicates sufficient artifact removal as well as
      physiological correspondence of VEPs in both periods. Simultaneous continuous VEP
      fMRI recordings are thus shown to be feasible.

PMID- 15954140
TI  - Methodological issues relating to in vivo cortical myelography using MRI.
AB  - The relationship between neocortical structure and function is a key area of
      research in neuroscience. Most studies of neural function, whether using
      neurophysiology or neuroimaging methods, are interpreted with relation to the
      underlying cortical myelo- and cytoarchitecture. For functional neuroimaging
      studies this often means using cytoarchitectonic maps based on the study of a
      limited number of brains, despite evidence for substantial interindividual
      variation. Improvements in MR technology, resulting in wider availability of high
      field MRI systems, have led to an increase in the achievable resolution in MR
      scans. Several groups have reported the in vivo detection of myelination patterns
      within the cortex, consistent with those observed in postmortem tissue. This
      leads to the possibility of predefining areas for fMRI analysis based on the
      cortical architecture. To do this it is essential to know, in a quantitative way,
      how reliably myeloarchitectonic areas and boundaries can be detected using MRI.
      Here we investigate the striate cortex, known to be coincident with V1, to assess
      the detectability of the stria of Gennari across V1 and across subjects. Under
      optimal conditions, 80% of the stria of Gennari was visualized using our
      methodology, although there was considerable variability in the level of
      detection across subjects. We discuss the limitations of the methodology and
      propose ways to improve the detection level of cortical myeloarchitecture more
      generally.

PMID- 15954139
TI  - Altered resting state networks in mild cognitive impairment and mild Alzheimer's
      disease: an fMRI study.
AB  - Activity and reactivity of the default mode network in the brain was studied
      using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals
      with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease
      (AD), and 41 healthy elderly controls (HC). The default mode network was
      interrogated by means of decreases in brain activity, termed deactivations,
      during a visual encoding task and during a nonspatial working memory task.
      Deactivation was found in the default mode network involving the anterior
      frontal, precuneus, and posterior cingulate cortex. MCI patients showed less
      deactivation than HC, but more than AD. The most pronounced differences between
      MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the
      reactivity and adaptation of the network. The default mode network response in
      the anterior frontal cortex significantly distinguished MCI from both HC (in the
      medial frontal) and AD (in the anterior cingulate cortex). The response in the
      precuneus could only distinguish between patients and HC, not between MCI and AD.
      These findings may be consistent with the notion that MCI is a transitional state
      between healthy aging and dementia and with the proposed early changes in MCI in
      the posterior cingulate cortex and precuneus. These findings suggest that altered
      activity in the default mode network may act as an early marker for AD pathology.

PMID- 15954141
TI  - Human brain activation during passive listening to sounds from different
      locations: an fMRI and MEG study.
AB  - Recent animal and human studies indicate the existence of a neural pathway for
      sound localization, which is similar to the "where" pathway of the visual system
      and distinct from the sound identification pathway. This study sought to
      highlight this pathway using a passive listening protocol. We employed fMRI to
      study cortical areas, activated during the processing of sounds coming from
      different locations, and MEG to disclose the temporal dynamics of these areas. In
      addition, the hypothesis of different activation levels in the right and in the
      left hemispheres, due to hemispheric specialization of the human brain, was
      investigated. The fMRI results indicate that the processing of sound, coming from
      different locations, activates a complex neuronal circuit, similar to the sound
      localization system described in monkeys known as the auditory "where" pathway.
      This system includes Heschl's gyrus, the superior temporal gyrus, the
      supramarginal gyrus, and the inferior and middle frontal lobe. The MEG analysis
      allowed assessment of the timing of this circuit: the activation of Heschl's
      gyrus was observed 139 ms after the auditory stimulus, the peak latency of the
      source located in the superior temporal gyrus was at 156 ms, and the inferior
      parietal lobule and the supramarginal gyrus peaked at 162 ms. Both hemispheres
      were found to be involved in the processing of sounds coming from different
      locations, but a stronger activation was observed in the right hemisphere.

PMID- 15954142
TI  - Repetition-induced changes in BOLD response reflect accumulation of neural
      activity.
AB  - Recent exposure to a stimulus improves performance with subsequent identification
      of that same stimulus. This ubiquitous, yet simple, memory phenomenon is termed
      priming and has been linked to another widespread phenomenon called repetition
      suppression, which is a repetition-induced reduction in human brain activation as
      measured using fMRI. Here, competing models of the neural basis of repetition
      suppression were tested empirically. In a backward masking paradigm, we found
      that effectively masked object stimuli showed repetition enhancement of brain
      activation instead of suppression. This finding is consistent with an
      Accumulation model, but is inconsistent with a Suppression model of neural
      activity. Enhanced activation and the improved behavioral performance usually
      associated with priming are both explained by a shift in peak latency of the
      population neural activity elicited during identification.

PMID- 15954143
TI  - Reply: Lack of association between progressive supranuclear palsy and arterial
      hypertension: a clinicopathological study.

PMID- 15954145
TI  - Aligning Au nanorods by using carbon nanotubes as templates.

PMID- 15954144
TI  - NeuroAIDS: contributions of the human immunodeficiency virus-1 proteins Tat and
      gp120 as well as CD40 to microglial activation.
AB  - Microglia are the resident phagocytes of the brain and are an important source of
      proinflammatory mediators. Human immunodeficiency virus (HIV)-1 infects the
      central nervous system early in the course of disease, and it is believed that
      this occurs, in part, through the transmigration of HIV-1-infected cells across
      the blood-brain barrier. Infected cells release viral proteins, such as Tat and
      gp120. After microglia interact with these proteins, they become activated and
      secrete chemokines; up-regulate key surface receptors, such as CD40, and also
      activate resident cells. This review focuses on the consequences of microglial
      activation in NeuroAIDS, with an emphasis on chemokine production and CD40 up
      regulation after interaction with tat or gp120. The importance of microglial CD40
      in two other neurological diseases, Alzheimer's disease and multiple sclerosis,
      is also discussed.

PMID- 15954146
TI  - Total synthesis of glycocinnasperimicin D.

PMID- 15954147
TI  - Enantio- and diastereoselective catalytic Mannich-type reaction of a glycine
      schiff base using a chiral two-center phase-transfer catalyst.

PMID- 15954148
TI  - A neutral mixed-valent conducting polymer formed by electron transfer between
      metal d and ligand pi orbitals.

PMID- 15954149
TI  - The binding of single-stranded DNA and PNA to single-walled carbon nanotubes
      probed by flow linear dichroism.
AB  - The binding of single-stranded DNAs and a neutral DNA analogue (peptide nucleic
      acid, PNA) to single-walled carbon nanotubes in solution phase has been probed by
      absorbance spectroscopy and linear dichroism. The nanotubes are solubilised by
      aqueous sodium dodecyl sulfate, in which the nucleic acids also dissolve. The
      linear dichroism (LD) of the nanotubes, when subtracted from that due to the
      nanotubes/nucleic acid samples, gives the LD of the bound nucleic acid. The
      binding of the single-stranded DNA to the single-walled nanotubes is quite
      different from that previously observed for double-stranded DNA. It is likely
      that the nucleic acid bases lie flat on the nanotube surface with the backbone
      wrapping round the nanotube at an oblique angle in the region of 45 degrees . The
      net effect is like beads on a string. The base orientation with the single
      stranded PNA is inverted with respect to that of the single-stranded DNA, as
      shown by their oppositely signed LD signals.

PMID- 15954150
TI  - Dramatic change in the tertiary structure of giant DNA without distortion of the
      secondary structure caused by pteridine-polyamine conjugates.
AB  - Pteridine-polyamine conjugates, such as 2-polyamine (1,3-diaminopropane and
      spermine) substituted 6,7-dimethyl-3H-pteridine-4-one, induce a folding
      transition of a giant DNA molecule more effectively than the corresponding
      polyamines. However, since neither a DNA high-temperature shift of denaturation
      (Tm) curve nor distortion of the UV/fluorescence spectra is observed in a mixture
      of these compounds with DNA, they do not interact with the DNA duplex strongly.

PMID- 15954151
TI  - Synthesis of the C(1)-C(11) polyene fragment of apoptolidin with a new sulfur
      dioxide-based organic chemistry.
AB  - A new sulfur dioxide-based organic chemistry has been developed as a novel
      approach for the stereoselective synthesis of polyene fragments based on our one
      pot, four-component synthesis of polyfunctional epsilon-alkanesulfonyl
      gamma,delta-unsaturated ketones. The flexibility and efficiency of this
      methodology are illustrated by the preparation of (+)-methyl (2E,4E,6E,8R,9S)-9
      {[(tert-butyl)dimethylsilyl]oxy}-2,4,6,8-tetramethyl-11-(triethylsilyl)undeca
      2,4,6-trien-10-ynoate, a synthetic intermediate of Nicolaou and co-workers, that
      corresponds to the C(1)-C(11) fragment of apoptolidin, which was used by the
      authors in their total synthesis of this promising anticancer agent.

PMID- 15954152
TI  - 2,5-Dioxido-1,4-benzoquinonediimine (H2L2-), a hydrogen-bonding noninnocent
      bridging ligand related to aminated topaquinone: different oxidation state
      distributions in complexes [{(bpy)2Ru}2(mu-H2L)]n (n=0,+,2+,3+,4+) and
      [{(acac)2Ru}2(mu-H2L)]m (m=2-,-,0,+,2+).
AB  - The symmetrically dinuclear title compounds were isolated as diamagnetic
      [(bpy)2Ru(mu-H2L)Ru(bpy)2](ClO4)2 (1-(ClO4)2) and as paramagnetic [(acac)2Ru(mu
      H2L)Ru(acac)2] (2) complexes (bpy=2,2'-bipyridine; acac- = acetylacetonate = 2,4
      pentanedionato; H2L = 2,5-dioxido-1,4-benzoquinonediimine). The crystal structure
      of 22 H2O reveals an intricate hydrogen-bonding network: Two symmetry-related
      molecules 2 are closely connected through two NH(H2L2-)O(acac-) interactions,
      while the oxygen atoms of H2L2- of two such pairs are bridged by an (H2O)8
      cluster at half-occupancy. The cluster consists of cyclic (H2O)6 arrangements
      with the remaining two exo-H2O molecules connecting two opposite sides of the
      cyclo-(H2O)6 cluster, and oxido oxygen atoms forming hydrogen bonds with the
      molecules of 2. Weak antiferromagnetic coupling of the two ruthenium(III) centers
      in 2 was established by using SQUID magnetometry and EPR spectroscopy. Geometry
      optimization by means of DFT calculations was carried out for 1(2+) and 2 in
      their singlet and triplet ground states, respectively. The nature of low-energy
      electronic transitions was explored by using time-dependent DFT methods. Five
      redox states were reversibly accessible for each of the complexes; all odd
      electron intermediates exhibit comproportionation constants K(c)>10(8). UV
      visible-NIR spectroelectrochemistry and EPR spectroscopy of the electrogenerated
      paramagnetic intermediates were used to ascertain the oxidation-state
      distribution. In general, the complexes 1n+ prefer the ruthenium(II)
      configuration with electron transfer occurring largely at the bridging ligand (mu
      H2Ln-), as evident from radical-type EPR spectra for 13+ and (+. Higher metal
      oxidation states (iii, iv) appear to be favored by the complexes 2m; intense long
      wavelength absorption bands and RuIII-type EPR signals suggest mixed-valent
      dimetal configurations of the paramagnetic intermediates 2+ and 2-.

PMID- 15954153
TI  - Methylene-azaphosphirane as a reactive intermediate.
AB  - Reaction of the transient phosphinidene complexes R-P=W(CO)5 with N-substituted
      diphenylketenimines leads unexpectedly to the novel 2-aminophosphindoles, as
      confirmed by an X-ray crystal structure determined for one of the derivatives.
      Experimental evidence for a methylene-azaphosphirane intermediate was found by
      using the iron-complexed phosphinidene iPr2N-P=Fe(CO)4, which affords the 2
      aminophosphindole together with the novel methylene-2,3-dihydro-1H
      benzo[1,3]azaphosphole. Analysis of the reaction pathways with DFT indicates that
      the initially formed methylene-azaphosphirane yields both phosphorus heterocycles
      by way of a [1,5]- or [1,3]-sigmatropic shift, respectively, followed by a H
      shift. Strain underlies both rearrangements, which causes these remarkably
      selective conversions that can be tuned by changing the substituents.

PMID- 15954154
TI  - Strategies for targeting protein-protein interactions with synthetic agents.
AB  - The development of small-molecule modulators of protein-protein interactions is a
      formidable goal, albeit one that possesses significant potential for the
      discovery of novel therapeutics. Despite the daunting challenges, a variety of
      examples exists for the inhibition of two large protein partners with low
      molecular-weight ligands. This review discusses the strategies for targeting
      protein-protein interactions and the state of the art in the rational design of
      molecules that mimic the structures and functions of their natural targets.

PMID- 15954155
TI  - Supramolecular coordination assemblies of dinuclear Fe(III) complexes.

PMID- 15954156
TI  - Proteomic analysis of redox- and ErbB2-dependent changes in mammary luminal
      epithelial cells using cysteine- and lysine-labelling two-dimensional difference
      gel electrophoresis.
AB  - Differential protein expression analysis based on modification of selected amino
      acids with labelling reagents has become the major method of choice for
      quantitative proteomics. One such methodology, two-dimensional difference gel
      electrophoresis (2-D DIGE), uses a matched set of fluorescent N
      hydroxysuccinimidyl (NHS) ester cyanine dyes to label lysine residues in
      different samples which can be run simultaneously on the same gels. Here we
      report the use of iodoacetylated cyanine (ICy) dyes (for labelling of cysteine
      thiols, for 2-D DIGE-based redox proteomics. Characterisation of ICy dye
      labelling in relation to its stoichiometry, sensitivity and specificity is
      described, as well as comparison of ICy dye with NHS-Cy dye labelling and several
      protein staining methods. We have optimised conditions for labelling of
      nonreduced, denatured samples and report increased sensitivity for a subset of
      thiol-containing proteins, allowing accurate monitoring of redox-dependent thiol
      modifications and expression changes. Cysteine labelling was then combined with
      lysine labelling in a multiplex 2-D DIGE proteomic study of redox-dependent and
      ErbB2-dependent changes in epithelial cells exposed to oxidative stress. This
      study identifies differentially modified proteins involved in cellular redox
      regulation, protein folding, proliferative suppression, glycolysis and
      cytoskeletal organisation, revealing the complexity of the response to oxidative
      stress and the impact that overexpression of ErbB2 has on this response.

PMID- 15954157
TI  - Determination of sulfates of androsterone and epiandrosterone in human serum
      using isotope diluted liquid chromatography-electrospray ionization-mass
      spectrometry.
AB  - A promising liquid chromatography-electrospray ionization-mass spectrometry (LC
      ESI-MS) for analysis of the sulfates of 5alpha-androgen, androsterone and
      epiandrosterone (A-S and EpiA-S) in human serum was developed. The method was
      used to assess one of the markers of 5alpha-reductase activity of males including
      patients with prostate cancer (PC). After deproteinization with acetonitrile, the
      androgen sulfates and the internal standard, [7,7,16,16
      2H4]dehydroepiandrosterone-S, were extracted from human serum using a solid-phase
      extraction cartridge and washed with hexane. The extract was reconstituted and
      applied to the LC/ESI-MS system operated in the selected ion monitoring mode. The
      method was validated over the range 0.02-5 microg/mL (A-S) and 0.005-1.5
      microg/mL (EpiA-S) using 10 microL of human serum. The method was a concise
      procedure without chemical or enzymatic hydrolysis of the conjugates,
      purification by high-performance liquid chromatography and/or derivatization, and
      proved to be satisfactory in its reproducibility and accuracy. The levels of
      these androgen sulfates tended to decrease during aging, and the A-S levels in
      the sera obtained from both healthy males and patients with PC were correlated
      with their EpiA-S levels.

PMID- 15954158
TI  - Synthesis of benzofurazan derivatization reagents for carboxylic acids and its
      application to analysis of fatty acids in rat plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - The derivatization regents for carboxylic acids, DAABD-AE (4-[2-(N,N
      dimethylamino)ethylaminosulfonyl]7-(2-aminoethylamino)-2,1,3-benzoxadiazole),
      MePZBD-AE ([4-(4-N-methyl)piperazinosulfonyl]-7-(2-aminoethylamino)-2,1,3
      benzoxadiazole) and APZBD-NHMe ([4-(4-N-aminoethyl)piperazinosulfonyl]-7
      methylamino-2,1,3-benzoxadiazole) were developed for electrospray ionization-mass
      spectrometry (ESI-MS). The derivatization reaction with fatty acids was completed
      at 60 degrees C within 30 min. The derivatives of fatty acids were separated on a
      reversed-phase column and detected with ESI-MS. The detection limits attained for
      fatty acids were femtomol range and the calibration curves were linear over the
      range from 0.1 to 100 pmol (r2 > 0.992) for DAABD-AE and MePZBD-AE. DAABD-NHMe
      was applied to the analysis of fatty acids in rat plasma samples.

PMID- 15954159
TI  - Investigation of copper-azamacrocyclic complexes by high-performance liquid
      chromatography.
AB  - The use of copper radioisotopes in imaging and therapy has prompted an increased
      interest in chelators which form stable copper complexes, such as Cu(II)
      azamacrocyclic complexes. The effects of charge, stability and the size of the
      macrocyclic backbone of the Cu(II)-azamacrocyclic complexes on biological
      behavior have been evaluated. Here we report a reversed-phase high-performance
      liquid chromatography (HPLC) method to separate several Cu(II)-azamacrocyclic
      complexes, including Cu(II) complexes of 1,4,8,11-tetraazacyclotetradecane
      1,4,8,11-tetraacetic acid (TETA), 4,11-bis(carboxymethyl)-1,4,8,11
      tetraazabicyclo[6.6.2]hexadecane (CB-TE2A) and 4,10-bis(carboxymethyl)-1,4,7,10
      tetraazabicyclo[5.5.2]tetradecane (CB-DO2A). Absorbance at 280 nm was used to
      monitor the complexes as they eluted from the reversed-phase column. The effects
      of the concentration of the buffer, the pH of the buffered mobile phase and the
      concentration of the organic modifier, methanol, on the separation were
      investigated. Separation of these copper complexes by ion-pair HPLC with the use
      of a mass spectrometry-compatible ion-pair reagent, triethylammonium acetate, in
      the mobile phase at pH 6.3 is also presented. The reversed-phase chromatographic
      conditions utilized also allow the pK(a)s of Cu-TETA and the log(k'w) values of
      Cu-CB-TE2A, Cu-TETA and Cu-CB-DO2A to be estimated.

PMID- 15954160
TI  - A high-performance liquid chromatographic method for determination of the
      niguldipine analogue DHP-014.
AB  - A simple and reliable reversed-phase high-performance liquid chromatography
      method was developed and validated for the determination of DHP-014, a
      niguldipine analogue with potent P-glycoprotein inhibitory and negligible calcium
      channel blocking properties, in rat plasma. DHP-014 and niguldipine hydrochloride
      (the internal standard) were extracted from rat plasma by liquid extraction using
      hexane. DHP-014 was then separated by HPLC on a C18 column and quantified by
      ultraviolet detection at 238 nm. The mobile phase consisted of acetonitrile
      aqueous 5 mM phosphate buffer (65:35, v/v) containing 0.4% (v/v) triethylamine
      adjusted to pH 7.0. The mean extraction efficiency of DHP-014 was 109.0 +/- 12.9,
      97.7 +/- 8.0 and 102.9 +/- 7.5% for DHP-014 concentrations of 10, 50 and 100 nM,
      respectively (n = 5). The method was linear over the concentration range 2.5-200
      nM with a regression coefficient of 0.998. The limit of detection of DHP-014 in
      rat plasma was 1.0 nM. The intra- and inter-day coefficients of variation for DHP
      014 in rat plasma were 4.7-7.9 and 6.9-9.9%, respectively. The intra- and inter
      day accuracy was 98.2-99.5 and 97.9-103%, respectively. The bioanalytical
      technique was used to determine DHP-014 in plasma samples in a pharmacokinetic
      study of DHP-014 administered to female Sprague-Dawley rats.

PMID- 15954161
TI  - Determination of rizatriptan in human plasma by liquid chromatographic
      eletrospray tandem mass spectrometry: application to a pharmacokinetic study.
AB  - A sensitive liquid chromatographic-tandem mass spectrometry(LC-MS/MS) method was
      developed for the determination of rizatriptan in human plasma. The analytes were
      extracted from plasma samples by liquid-liquid extraction, separated on a Zorbax
      XDB C8 column (150 x 4.6 mm i.d.) and detected by tandem mass spectrometry with
      an electrospray ionization interface. Zomitriptan was used as the internal
      standard. The method had a lower limit of quantitation of 50 pg/mL for
      rizatriptan, which showed more sensitivity and speed of analysis compared with
      reported methods. The within- and between-day precision was measured to be below
      11.71% and accuracy between -5.87 and 0.86% for all quality control samples. This
      quantitation method was successfully applied to the evaluation of the
      pharmacokinetic profiles of rizatriptan after single oral administration of 5, 10
      and 15 mg rizatriptan tablets to 10 healthy volunteers (five males and five
      females).

PMID- 15954162
TI  - Pharmacokinetics of timolol in aqueous humor sampled by microdialysis after
      topical administration of thermosetting gels.
AB  - In order to develop a thermosetting gel-based formulation, the ocular
      pharmacokinetics of timolol was studied utilizing microdialysis sampling
      technique after topical administration. A linear microdialysis probe was
      characterized and implanted in the anterior chamber of a rabbit. Dialysate
      samples collected from the aqueous humor (AH) were directly injected into the
      HPLC system without any pre-treatment and no interference was observed in the
      blank sample. The measured in vitro recovery of the probe was 57.67%; however,
      the in vivo recovery significantly decreased to 16.78% when assessed by the
      retrodialysis method, which was used to calculate the timolol concentration in
      AH. Although in the initial 15 min the drug concentrations in AH were comparable
      to that of the timolol solution, increased Cmax and significantly improved ocular
      bioavailability were obtained for the gel. When sodium deoxycholate (DC) was
      incorporated in the gel as a penetration enhancer, a 2-fold increment in the
      ocular bioavailability was achieved with an increased Cmax and significantly
      suspended Tmax. The results demonstrated that microdialysis coupled to HPLC is a
      powerful tool to investigate the ocular pharmacokinetic, and hence facilitates
      the design of ophthalmic formulations.

PMID- 15954163
TI  - Liquid chromatographic assay for the protease inhibitor atazanavir in plasma.
AB  - Atazanavir is the most recently introduced protease inhibitor for the suppression
      of the anti-human immunodeficiency virus. A sensitive and selective reversed
      phase liquid chromatographic assay for this drug in human plasma has been
      developed and validated. Atazanavir was isolated from a 500 microL plasma sample
      using liquid-liquid extraction with dichloromethane. After evaporation and
      reconstitution of the extract the sample was analysed using liquid chromatography
      and ultraviolet detection at 280 nm. In the evaluated concentration range (44
      4395 ng/mL atazanavir), intra-day precisions were < or =7% and inter-day
      precisions were < or =14%. Accuracies between 96 and 106% were found. The lower
      limit of quantification was 44 ng/mL with an intra-day precision of 7%, an inter
      day precision of 14% and an accuracy of 87%. There was no interference from 32
      tested potentially co-administrated drugs and metabolites. The usefulness of the
      assay was demonstrated for samples obtained from an HIV-infected patient treated
      with atazanavir.

PMID- 15954164
TI  - Some advances in the knowledge of grape, wine and distillates chemistry as
      achieved by mass spectrometry.
AB  - Mass spectrometry plays a very important role in acquiring knowledge of the
      chemistry of grape and its derivative products. By liquid mass spectrometry,
      anthocyanins of grape were studied, and in hybrid grape extracts, delphinidin,
      cyanidin, petunidin and malvidin 3-O-(6-O-p-coumaroyl)-5-O-diglucosides were
      found. A semiquantitative procedure to estimate the amounts and percentages of
      monoglucoside and diglucoside anthocyanins without chromatography was developed.
      By gas chromatography mass spectrometry (GC/MS), aroma compounds of grape, wine
      and the distillate Italian grappa were studied, and molecular structures
      characterized. The representative aroma profile of Muscat grape was characterized
      by 23 terpenols, present in both free and bonded form, and direct correlation
      between aroma and genetic profile permitted to distinguish between different
      Muscat grape varieties. Aroma of Italian grappa resulted from and was
      characterized by several compounds linked to the grape variety, such as
      vitispiranes, terpenols, ethyl cinnamate, salicylic esters, benzaldehyde and
      farnesol. Synthesis of O-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine (PFBOA)
      derivatives and GC/MS analysis resulted in a sensitive and selective method to
      study carbonyl compounds at the low levels occurring in wine.

PMID- 15954165
TI  - ERbeta isoform expression in colorectal carcinoma: an in vivo and in vitro study
      of clinicopathological and molecular correlates.
AB  - Colorectal carcinoma shows several sex-related differences with regard to
      incidence, response to chemotherapy and microsatellite instability. These
      differences may relate to differential expression of ERbeta1 (wild-type) as well
      as the truncated ERbeta2 and ERbeta5 splice variant isoforms, which have recently
      been detected in normal and malignant colorectal epithelium. This hypothesis was
      tested through the study of ERbeta isoform protein and/or mRNA expression amongst
      91 primary colorectal carcinoma cases and 20 colorectal carcinoma cell lines.
      Study of the latter showed an absolute correlation between mRNA and protein
      expressions for ERbeta1 and ERbeta2. ERbeta1 and ERbeta2 protein expression was
      lost in 22% and 49%, respectively, of the primary colorectal carcinomas. By
      contrast, ERbeta5 expression was found in all primary colorectal carcinomas and
      all colorectal carcinoma cell lines studied. Lower ERbeta1 protein expression was
      associated with poorer differentiation, higher pT stage and absence of
      microsatellite instability. Higher ERbeta2 protein expression was associated with
      right-sided location and presence of lymph node metastases. Protein expression of
      ERbeta1 correlated positively with expression of the oestrogen-responsive protein
      trefoil factor 1 (TFF1). There was no correlation between ERbeta protein isoform
      expression and response to 5-fluorouracil therapy, tumour proliferation, or
      thymidylate synthase expression. These data suggest that ERbeta1 and/or ERbeta2
      isoform expression may have prognostic value and may explain sex-related
      differences in microsatellite instability and colorectal carcinoma. The opposing
      associations shown by ERbeta1 and/or ERbeta2 in relation to colorectal carcinoma
      are in keeping with differential activities shown by the two isoforms.

PMID- 15954166
TI  - Chromatographic characterization of substance P endopeptidase in the rat brain
      reveals affected enzyme activity following heat stress.
AB  - This paper describes a study of substance P endopeptidase (SPE)-like activity in
      various regions of the brain from male rats subjected to heat stress (HS). The
      enzyme activity was found to be affected in several brain areas including
      cerebellum, cerebral cortex, hippocampus, hypothalamus[sol ]thalamus and the
      spinal cord following HS. Significant increases in SPE activity were observed in,
      for example, hippocampus and the spinal cord. SPE-containing extracts from
      hippocampus were pooled and subsequently purified by size exclusion
      chromatography (using a Superdex 75 HR column) and by anion-exchange
      chromatography (using Resource Q column). The gel permeation chromatography
      separated the SPE-like activity into two fractions, one of which was suggested to
      be identical to neutral endopeptidase owing to its molecular size and inhibitory
      profile. The other active enzyme fraction behaved in conformity with SPE,
      previously identified in human cerebrospinal fluid. The activity of the purified
      fraction of these two enzymes was found to be increased (27%) in HS-treated
      animals.

PMID- 15954167
TI  - Interactions of drugs and an oligonucleotide with charged membranes analyzed by
      immobilized liposome chromatography.
AB  - We studied the effect of charged lipids or detergent on the retention of drugs
      and an oligonucleotide by immobilized liposome chromatography to characterize
      solute-membrane interactions. This is a novel approach in analysis of
      oligonucleotide-liposome interactions. The charged lipids (phosphatidylserine or
      distearoyltrimethylammoniumpropane) or detergent (sodium dodecylsulfate)
      interacted electrostatically in a concentration-dependent matter with the
      solutes. The oligonucleotide ions presumably bound to the liposomes by multipoint
      interactions, which was saturable. Sodium dodecylsulfate seemed to affect the
      drug-membrane interactions more strongly than phosphatidylserine did, probably
      due to different positioning in the bilayer.

PMID- 15954168
TI  - Simultaneously quantifying parent drugs and screening for metabolites in plasma
      pharmacokinetic samples using selected reaction monitoring information-dependent
      acquisition on a QTrap instrument.
AB  - Bioanalytical support of plasma pharmacokinetic (PK) studies for drug discovery
      programs primarily involves the quantitative analysis of dosed compounds using
      liquid chromatography/atmospheric pressure ionization tandem mass spectrometry
      (LC/MS/MS) operated in selected reaction monitoring (SRM) mode. However, there is
      a growing need for information on the metabolism of new chemical entities (NCEs),
      in addition to the time-concentration profiles from these studies. In this paper,
      we present a novel approach to not only quantify parent drugs with SRM, but also
      simultaneously screen for metabolites using a hybrid triple quadrupole/linear ion
      trap (QqQ(LIT)) instrument. This was achieved by incorporating both the
      conventional SRM-only acquisition of parent compounds and the SRM-triggered
      information-dependent acquisition (IDA) of potential metabolites within the same
      scan cycle during the same LC/MS/MS run. Two test compounds were used to
      demonstrate the applicability of this approach. Plasma samples from PK studies
      were processed by simple protein precipitation and the supernatant was diluted
      with water before injection. The fast scanning capability of the linear ion trap
      allowed for the information-dependent acquisition of metabolite MS/MS spectra (<1
      s/scan), in addition to the collection of adequate data points for SRM-only
      channels. The MS/MS spectra obtained from potential metabolites in post-dose
      samples correlated well with the spectra of the parent compounds studied,
      therefore providing additional confirmatory structure information without the
      need for repetitive analyses. Relative quantitative time-concentration profiles
      of identified metabolites were also obtained. Furthermore, this articulated
      SRM+SRM-IDA approach generated equivalent quantitative results for parent
      compounds to those obtained by conventional SRM-only analysis. This approach has
      been successfully used to support discovery PK screening programs.

PMID- 15954169
TI  - Some fundamental and technical aspects of the quantitative analysis of
      pharmaceutical drugs by matrix-assisted laser desorption/ionization mass
      spectrometry.
AB  - The purpose of the present paper was to study some of the underlying physical and
      technical aspects of high-throughput quantitative matrix-assisted laser
      desorption/ionization (MALDI) of small drug molecules. A prototype MALDI-triple
      quadrupole instrument equipped with a high repetition rate laser was employed.
      Initially, the detection limits and dynamic ranges for the quantitation of four
      drugs (quinidine, danofloxacin, ramipril and nadolol) were determined. Internal
      standards were carefully chosen for each of these analytes in terms of structure
      similarity and fragmentation pathways. Three organic matrices were tested for
      these assays, resulting in different crystallization behaviors and measurement
      reproducibilities. alpha-Cyano-4-hydroxycinnamic acid yielded the best results
      and was subsequently employed for the quantitative determination of all four
      analytes. Further experiments considered the role of laser energy and pulse rate
      on the ablated areas as well as ion signals. Light microscope and scanning
      electron microscope images allowed the examination of the ablated area of the
      MALDI spots. The images showed convincing evidence that the ablated area was
      virtually void of crystals after analysis, with no preferential removal of
      material in the center of the laser's path. Average values for the amount of
      material ablated were determined to be 3.9+/-0.5% of the total spot size, and as
      low as 19.5 attomoles of analyte were detectable for our most sensitive analyte,
      ramipril. It was calculated that, under these assay conditions, it was possible
      to accurately quantify less than 1 femtomole of all analytes with the use of
      appropriately pure internal standards. These studies showed very promising
      results for the quantitative nature of MALDI for small molecules with molecular
      weights less than 500 Da.

PMID- 15954171
TI  - A strategy for identification of drug metabolites from dried blood spots using
      triple-quadrupole/linear ion trap hybrid mass spectrometry.
AB  - Discovery stage studies that address issues of absorption, distribution,
      metabolism and excretion (ADME) are vital for lead optimization resulting in new
      drug candidates. Often pharmacokinetics (PK) is assessed in these experiments
      without regard for the metabolism of the compound or the potential for
      metabolites to circulate in vivo. This work presents a strategy for drug level
      determination and detection of metabolites using dried blood spots for sample
      collection. Initially, metabolites are detected from microsomal incubations and
      characterized using tandem mass spectrometry. Data dependent enhanced MS and
      enhanced product ion (EMS-EPI) scanning with dynamic background subtraction was
      used on a hybrid quadruple linear ion trap mass spectrometer. On-the-fly
      background subtraction greatly improved the detection of metabolites. These data
      were used to build a multiple reaction monitoring (MRM) method for the parent and
      metabolites. MRM-EPI scanning was used to analyze the extracted dried blood spots
      from the PK study. Circulating metabolites were detected using MRM and their
      identities confirmed on the basis of fragment ion spectra collected
      simultaneously. The use of dried blood spots provides a means for re-analysis of
      PK samples for metabolite identification without the need for complex sample
      storage and preparation. Both parent compound and metabolite information can be
      collected in these studies, resulting in a savings of time and resources.

PMID- 15954173
TI  - Intact human holo-transferrin interaction with oxaliplatin.
AB  - We report the interaction of intact human holo-transferrin (holo-Tf) with
      oxaliplatin (an anticancer drug), and the characterization of a complex composed
      of (1:1) intact holo-Tf and the parent oxaliplatin molecule using
      nanoelectrospray ionization quadrupole time-of-flight mass spectrometry (nanoESI
      QTOF-MS). The molecular weight of this complex was determined to be 80,077 Da,
      which was an increase of 397 mass units compared to the protein alone (79,680
      Da), suggesting that a parent drug molecule was bound to the intact protein. We
      further examined the interaction between the intact protein and oxaliplatin using
      size-exclusion high-performance liquid chromatography/inductively coupled plasma
      mass spectrometry (HPLC/ICPMS). The protein complex and free oxaliplatin were
      separated by HPLC and quantitatively determined by simultaneous monitoring of
      both 195Pt and 56Fe using ICPMS. The HPLC/ICPMS detected both Pt and Fe signals
      at retention time of 2.6 min, identifying the protein-drug complex. The Fe signal
      at 2.6 min did not change with the increase in incubation time of the reaction
      mixture containing holo-Tf and oxaliplatin, while the Pt signal at the same
      retention time increased over time, further demonstrating that the formation of
      this complex does not affect the protein-bound Fe. The binding constant of the
      (1:1) intact human holo-Tf-oxaliplatin complex was determined to be 7.7x10(5) M
      1. Both nanoESI-MS and HPLC/ICPMS results support that the holo-Tf and parent
      oxaliplatin molecules form complexes through non-covalent binding, suggesting
      that holo-Tf may be a useful carrier for oxaliplatin delivery.

PMID- 15954174
TI  - Alteration of the carbon and nitrogen stable isotope composition of beef by
      substitution of grass silage with maize silage.
AB  - This study investigated the effect of substituting grass silage (C3
      photosynthetic plant product) with maize silage (C4 photosynthetic plant product)
      on the natural abundance carbon (delta13C) and nitrogen (delta15N) stable isotope
      composition of bovine muscle tissue. Forty-five continental crossbred heifers
      were assigned to one of three diets consisting of 3 kg of a barley-based
      concentrate plus grass silage, maize silage or an equal mixture (dry matter
      basis) of grass silage and maize silage, fed ad libitum, for 167 days.
      Substitution resulted in less negative delta13C values (P<0.001) in lipid-free
      muscle and in lipid, and also a lower delta15N (P<0.001) in lipid-free muscle.
      Feeding of maize silage was clearly reflected in the delta13C of muscle, with
      each 10% difference in the dietary C4 carbon intake resulting in a 0.9 to 1.0 per
      thousand shift of delta13C in lipid-free muscle and a 1.0 to 1.2 per thousand in
      lipid. Minimum detectable mean differences (95% confidence, power 0.80, n=15) in
      this experiment were about 0.5 per thousand and 1.0 per thousand for delta13C of
      lipid-free muscle and lipid, respectively, and about 0.5 per thousand for
      delta15N of lipid-free muscle. The power analysis presented here is useful for
      estimating minimum isotopic differences that can be detected between any two
      groups of beef samples with a given number of replicates. It is concluded that
      carbon stable isotope ratio analysis of meat can be used to quantify C3/C4
      dietary constituents in beef production.

PMID- 15954175
TI  - First results of a quantitative study of DNA adducts of melphalan in the rat by
      isotope dilution mass spectrometry using capillary liquid chromatography coupled
      to electrospray tandem mass spectrometry.
AB  - Rats were intravenously injected with a single high dose (10 mg/kg) of the
      alkylating agent melphalan in order to study DNA-adduct formation. Quantitation
      of a dGuo-melphalan adduct was done by isotope dilution mass spectrometry using
      capillary liquid chromatography/mass spectrometry (LC/MS) and [15N5]-labeled dGuo
      melphalan as internal standard. DNA-adduct levels were studied in bone marrow,
      liver and kidney. The instrumental detection limit of the method was determined
      to be 900 fg (S/N 3, pure standard). These first results clearly show a 10 times
      higher adduct level in bone marrow compared to kidney and a 6 times higher level
      compared to liver. More experiments will be necessary to gather more information
      on the pharmacokinetics of melphalan-DNA adducts under in vivo conditions.

PMID- 15954176
TI  - Analysis of 7-methylguanine using isotope dilution and gas
      chromatography/electron-capture negative chemical ionization mass spectrometry.
AB  - This paper presents results obtained for in vivo endogenous and exogenous 7
      methylguanine (7-MG) analyzed using a method incorporating gas chromatography
      with electron-capture negative chemical ionization mass spectrometry and isotope
      dilution (GC/EC-ID-MS). 13C4-Labeled 7-MG was synthesized to serve as an internal
      standard to improve accuracy of quantitation, and was used to analyze 7-MG in
      livers of control mice and dacarbazine-treated mice. The results confirm that 7
      MG in tissue DNA can be measured using this GC/EC-ID-MS method with excellent
      sensitivity and specificity. Administration of 0, 30, and 60 mg/kg dacarbazine to
      mice led to dose-dependent increases in the formation of 7-MG. The results
      indicate that this method could be applied to the analysis of endogenous and
      exogenous 7-MG in human tissues for future molecular epidemiology studies on
      potential health effects caused by methylating agents.

PMID- 15954177
TI  - Electron ionization mass spectral fragmentation of cholestane-3beta,4alpha,5alpha
      triol and cholestane-3beta,5alpha,6alpha/beta-triol bis- and tris-trimethylsilyl
      derivatives.
AB  - The electron ionization (EI) mass spectral fragmentation of the bis- and tris
      trimethylsilyl derivatives of cholestane-3beta,4alpha,5alpha-triol, cholestane
      3beta,5alpha,6beta-triol and cholestane-3beta,5alpha,6alpha-triol was
      investigated. The EI mass spectrum of the 3beta,4alpha-bis-trimethylsilyl
      derivative of cholestane-3beta,4alpha,5alpha-triol exhibits interesting fragment
      ions at m/z 142 and 332 resulting from the initial loss of TMSOH between the
      carbons 2 and 3 and subsequent retro-Diels-Alder (RDA) cleavage of the ring A.
      Trimethylsilyl transfer between the 4alpha- and the 5alpha-hydroxy groups acts
      significantly before RDA cleavage affording an ion at m/z 404. Complete
      silylation of cholestane-3beta,4alpha,5alpha-triol strongly stabilizes the
      molecule, affording an abundant molecular ion at m/z 636 and decreasing the
      abundance of the RDA cleavage. Loss of water (from the non-silylated 5alpha
      hydroxy group) plays a very important role during the decomposition of the
      molecular ion of 3beta,6alpha/beta-bis-trimethylsilyl derivatives of cholestane
      3beta,5alpha,6alpha/beta-triols. These derivatives appear to be very useful in
      assigning the configuration of the carbon 6. This assignment is based on the
      abundance of the fragment ions at m/z 321, 367 and 403, which are more prominent
      in the EI mass spectrum of the beta-isomer. In contrast, EI mass spectra of the
      tris-trimethylsilyl derivatives of cholestane-3beta,5alpha,6beta-triol and
      cholestane-3beta,5alpha,6alpha-triol differ only slightly and appear to be poorly
      informative.

PMID- 15954180
TI  - A gas chromatographic/mass spectrometric method for tracing the microbial
      conversion of glucose into amino sugars in soil.
AB  - Amino sugars in soils are heterogeneous and have been used as microbial residue
      biomarkers to investigate the microbial contribution to soil organic matter.
      However, it is not clear what the available carbon source is and how glucose is
      utilized for the synthesis of soil amino sugars. This paper presents a new gas
      chromatography/mass spectrometry (GC/MS) approach for the identification of 13C
      incorporation into three amino sugars, D-glucosamine, D-galactosamine, and
      muramic acid, in soil incubated with U-13C-glucose. Method evaluation showed that
      the chemical ionization (CI) mode was suitable for all these amino sugars, but
      that electron impact (EI) mode was applicable only to glucosamine and
      galactosamine. The 13C conversion rate was estimated based on the abundance ratio
      of the ions corresponding to the masses of the ions F+n and F (where n is the
      skeleton carbon number in the fragment ions F of the amino sugars) and calculated
      as atom percentage excess. The reproducibility of the method was excellent and
      clearly adequate for the present purpose. In addition, the new approach is highly
      accurate as tested with mixtures of U-13C-glucose and natural glucose.

PMID- 15954179
TI  - Liquid chromatography/electrospray ionization mass spectrometry method for the
      quantification of valproic acid in human plasma.
AB  - A simple, sensitive and rapid liquid chromatography/electrospray ionization mass
      spectrometry (LC/ESI-MS) method was developed and validated for the
      quantification of valproic acid, an antiepileptic drug, in human plasma using
      benzoic acid as internal standard (IS). Following solid-phase extraction, the
      analytes were separated using an isocratic mobile phase on a reversed-phase C18
      column and analyzed by MS in the single ion monitoring mode using the respective
      [M-H]- ions, m/z 143 for valproic acid and m/z 121 for the IS. The assay
      exhibited a linear dynamic range of 0.5-60 microg/mL for valproic acid in human
      plasma. The lower limit of quantification was 500 ng/mL with a relative standard
      deviation of less than 10%. Acceptable precision and accuracy were obtained for
      concentrations over the standard curve range. The average absolute recoveries of
      valproic acid and the IS from spiked plasma samples were 96.1+/-4.2 and 95.6+/
      2.7%, respectively. A run time of 4.5 min for each sample made it possible to
      analyze more than 250 human plasma samples per day. The validated method has been
      successfully used to analyze human plasma samples for application in
      pharmacokinetic, bioavailability and bioequivalence studies.

PMID- 15954183
TI  - At issue: The future of cognitive rehabilitation of schizophrenia.
AB  - Cognitive rehabilitation is becoming an increasingly popular intervention in
      treatment programs for people with schizophrenia. Despite this increased
      acceptance, however, the evidence base on its effectiveness is not impressive.
      Moreover, given the evidence of cognitive recovery in treated patients who do not
      receive cognitive rehabilitation--from newer medications and from other evidence
      based psychosocial interventions--it is not clear whether cognitive
      rehabilitation is worth its expense in time and resources. We believe that the
      slow progress in the field of cognitive rehabilitation of schizophrenia is
      related to failure to address several critical issues: (1) the importance of
      manipulating stimulus and context structure in rehabilitative interventions; (2)
      the need to base a cognitive rehabilitation of schizophrenia on cognitive
      neuroscience as opposed to neuropsychology; (3) the importance of systematically
      addressing motivation, self-esteem, and affective factors when designing
      cognition-enhancing interventions; (4) the need to move beyond one-size-fits-all
      interventions and develop individualized treatments; and (5) the need to address
      abnormalities in the experience of the self when designing interventions to
      optimize cognitive and behavioral performance. Suggestions for addressing these
      issues are discussed.

PMID- 15954181
TI  - Automatic repositioning of single voxels in longitudinal 1H MRS studies.
AB  - An automatic procedure, allowing the prospective registration of brain MRI images
      and the acquisition of nearly identical brain volumes (coverage and orientation)
      in longitudinal exams, is presented. This procedure, based on a fast registration
      algorithm and a tailored pulse sequence, is used to reposition single voxels for
      1H MRS data acquired in vivo. The impact of the repositioning method on the
      extent of voxel overlap and on the reproducibility of metabolite concentration
      measurements is studied. A statistically significant increase in voxel overlap
      and generally decreased short-term measurement variability (decreased
      coefficients of variation and increased reproducibility coefficients) are
      observed. Differences in the long-term variances of metabolite concentrations and
      concentration ratios measured using the eye and automatic repositioning scheme,
      however, do not reach statistical significance. The improved workflow associated
      with the use of the automatic repositioning process, which obviates the need for
      skilled operator intervention for voxel repositioning, suggests that approaches
      similar to the one presented here may be a standard element in tomorrow's
      longitudinal MRI and MRS exams.

PMID- 15954184
TI  - Performance of schizophrenia patients on time-, event-, and activity-based
      prospective memory tasks.
AB  - The present study aimed to determine whether individuals with long-term
      schizophrenia have impaired prospective memory (PM), the ability to remember to
      perform intended actions in the future. Three PM tasks (time-, event-, and
      activity-based) were administered to 60 schizophrenia patients and 60 matched
      controls. Patients performed significantly more poorly than controls on all three
      tasks. The between-group difference was disproportionately larger on the time
      based task, a task that required a prefrontal lobe process called self-initiated
      retrieval. To examine the relationship between PM and prefrontal lobe functions,
      subjects were also administered the Design Fluency Test (DFT), the Tower of
      London (TOL), and the Wisconsin Card Sorting Test (WCST). For patients,
      performance on the event-based task was found to correlate significantly with
      performance on the DFT, and performance on the time-based task was found to
      correlate significantly with performance on the TOL. Results of this study
      support the importance and contribution of prefrontal lobe processes in
      prospective remembering and have implications for the assessment and treatment of
      individuals with schizophrenia.

PMID- 15954185
TI  - Dynamic testing in schizophrenia: does training change the construct validity of
      a test?
AB  - Dynamic testing typically involves specific interventions for a test to assess
      the extent to which test performance can be modified, beyond level of baseline
      (static) performance. This study used a dynamic version of the Wisconsin Card
      Sorting Test (WCST) that is based on cognitive remediation techniques within a
      test-training-test procedure. From results of previous studies with schizophrenia
      patients, we concluded that the dynamic and static versions of the WCST should
      have different construct validity. This hypothesis was tested by examining the
      patterns of correlations with measures of executive functioning, secondary verbal
      memory, and verbal intelligence. Results demonstrated a specific construct
      validity of WCST dynamic (i.e., posttest) scores as an index of problem solving
      (Tower of Hanoi) and secondary verbal memory and learning (Auditory Verbal
      Learning Test), whereas the impact of general verbal capacity and selective
      attention (Verbal IQ, Stroop Test) was reduced. It is concluded that the
      construct validity of the test changes with dynamic administration and that this
      difference helps to explain why the dynamic version of the WCST predicts
      functional outcome better than the static version.

PMID- 15954186
TI  - Latent inhibition and overswitching in schizophrenia.
AB  - Attention disorders in schizophrenia are manifested in two different ways. On the
      one hand, the schizophrenia patient tends to keep a learned response even after
      it ceases to be relevant (perseveration). On the other hand, the schizophrenia
      patient tends to replace an adaptive response without being given a reason to do
      so (overswitching). In the present study, overswitching was investigated in
      relation to latent inhibition (LI), which is the normal ability to ignore
      nonrelevant stimuli. A new tool--the Combined Attention Test--was used for this
      purpose in a group of 41 unmedicated schizophrenia patients, divided into
      subgroups of patients with predominantly positive and negative symptoms, and 24
      normal controls. The results show that positive schizophrenia patients, who
      exhibited high levels of overswitching, also revealed impaired LI, while the
      negative schizophrenia group, as well as normal controls, exhibited intact LI.
      These findings suggest that overswitching is a specific attention deficit in
      positive schizophrenia. We discuss the possibility that impaired LI is a
      consequence of overswitching and comment on the putative neurophysiology.

PMID- 15954187
TI  - The role of attention in affect perception: an examination of Mirsky's four
      factor model of attention in chronic schizophrenia.
AB  - Attentional skills among people with schizophrenia may be related to deficits in
      affect perception. Such deficits can dramatically inhibit appropriate social
      functioning. We examined attention and affect perception in a sample of 65 people
      diagnosed with chronic schizophrenia. We used Mirsky's four factor model of
      attention to assess attentional functioning. To measure affect perception, we
      used two reliable measures of emotion recognition, the Bell-Lysaker Emotion
      Recognition Test and the Face Emotion Identification Test. Multiple regression
      analysis showed that all four attentional factors and a diagnosis of paranoid
      schizophrenia were significantly predictive of affect perception scores. In
      contrast, psychiatric symptoms, medication levels, demographic variables, verbal
      fluency, and face recognition scores were not predictive of affect perception
      scores. The four factors of attention accounted for 78 percent of the variance in
      affect perception scores. These results emphasize the role that attentional
      abilities play in affect perception for people with schizophrenia.

PMID- 15954188
TI  - First person account: schizophrenia and motherhood.
AB  - With this article I want to give insight into what having children and dealing
      with schizophrenia is like. I go from a young woman wanting to experience
      motherhood, to being diagnosed with schizophrenia, to marrying and having two
      children. It is not easy dealing with schizophrenia and mothering, but the
      rewards are wonderful. In my case, I had one very serious schizophrenia episode,
      and I became homeless and my children went to live with their father. I
      eventually got better and reunited with my children, but our lives had changed.
      In this article I describe the adjustments we all had to make, the heartaches,
      the struggles, and finally the love that has prevailed. Today, especially with
      the newer medications, more persons suffering with mental illness are marrying,
      and the possibility of starting families is very real. Perhaps a young person
      with a diagnosis of mental illness will read my factual account, and it will help
      her to make a decision that will change the rest of her life. In closing the
      article, I raise the question, "If I had to do it over again, would I?" I also
      share the reason for my decision.

PMID- 15954189
TI  - Sexuality and schizophrenia: a review.
AB  - Sexual functioning has received little attention as an important aspect of
      patient care for those suffering from severe mental disorders such as
      schizophrenia. Yet, it has been implicated as one of the major factors
      contributing to noncompliance with antipsychotic medications and is documented by
      people with schizophrenia to be one of the areas of treatment with the most unmet
      needs. A stronger focus on sexuality and preventing sexual dysfunction in
      schizophrenia would likely be a major benefit for improving treatment. This
      review will describe possible mechanisms for sexual dysfunction, describe sexual
      disturbances that have been documented in the literature of people who have
      schizophrenia, and summarize and discuss assessment measures available. Moreover,
      a focus on second-generation antipsychotics (SGA) and their association with
      sexual functioning is described. Each SGA (clozapine, risperidone, olanzapine,
      quetiapine, ziprasidone, and aripiprazole) will be described for its prolactin
      effects, documented sexual disturbances associated with use, and product labeling
      regarding sexual function. Treatment options and psychosocial issues pertaining
      to sexuality also are presented.

PMID- 15954190
TI  - Elevated levels of schizotypal features in parents of patients with a family
      history of schizophrenia spectrum disorders.
AB  - There is some evidence that schizotypal traits are related to a genetic or
      familial liability to develop schizophrenia. However, it is unclear whether the
      number of schizotypal traits is elevated in parents of schizophrenia patients
      compared with controls. This study used the Schizotypal Personality Questionnaire
      to investigate the difference in number of schizotypal traits between both
      parents of 36 patients with schizophrenia (n = 72 persons) and 26 healthy married
      control couples (n = 52 persons). Parents of patients had a lower score on the
      positive dimension of schizotypy than healthy controls. There was no difference
      on the negative or disorganization dimension between groups. The difference on
      the positive dimension might have been caused by a difference in response style
      between parents of patients and controls due to the fact that parents are more
      familiar with schizophrenia than controls. Of interest, parents with a family
      history of schizophrenia spectrum disorders had more positive and negative
      schizotypal traits than parents without a family history of schizophrenia
      spectrum disorders. Because these two groups of parents differ in only genetic
      risk, not familiarity with schizophrenia, results suggest that the negative and
      positive dimension of schizotypy are related to a familial or genetic
      vulnerability to schizophrenia.

PMID- 15954191
TI  - The correlates of comorbid antisocial personality disorder in schizophrenia.
AB  - More than 15 years ago, findings from the Epidemiological Catchment Area Study
      indicated that antisocial personality disorder (APD) is more prevalent among
      persons with schizophrenia than in the general population. The present study
      analyzed data from a multisite investigation to examine the correlates of APD
      among 232 men with schizophrenic disorders, three-quarters of whom had committed
      at least one crime. Comparisons of the men with and without APD revealed no
      differences in the course or symptomatology of schizophrenia. By contrast,
      multivariate models confirmed strong associations of comorbid APD with substance
      abuse, attention/concentration problems, and poor academic performance in
      childhood; and in adulthood with alcohol abuse or dependence and deficient
      affective experience (a personality style indexed by lack of remorse or guilt,
      shallow affect, lack of empathy, and failure to accept responsibility for one's
      own actions). At first admission, men with schizophrenia and APD presented a long
      history of antisocial behavior that included nonviolent offending and substance
      misuse, and an emotional dysfunction that is thought to increase the risk of
      violence toward others. Specific treatments and management strategies are
      indicated.

PMID- 15954192
TI  - Suicide in schizophrenia: a retrospective case-control study of 51 suicides.
AB  - The aim of this study was to identify factors associated with suicide in patients
      with schizophrenia who required inpatient admission and to compare these factors
      with the risk profile of patients with other diagnoses also requiring inpatient
      care. A retrospective, matched case-control study of 51 patients with
      schizophrenia requiring psychiatric inpatient care was undertaken. A priori
      specified risk factors were investigated within the schizophrenia group and
      compared with those of patients with other psychiatric diagnoses. The results
      show that previous suicide attempts are associated with an increased risk of
      suicide across all diagnoses. The presence of depressive symptoms and involvement
      of police with the index admission become more significant factors in patients
      with schizophrenia, compared to those with other diagnoses. Supportive mental
      health accommodation is associated with a reduced risk of suicide. Suicide of
      individuals is difficult to predict in patients with schizophrenia. Young men
      appear particularly vulnerable at times of inpatient care. Depressive symptoms
      and previous suicide attempts are significant risk factors.

PMID- 15954193
TI  - Deficit versus negative syndrome in schizophrenia: prediction of attentional
      impairment.
AB  - Findings on neuropsychological associates of the negative syndrome of
      schizophrenia have been inconsistent. The "deficit syndrome," a
      reconceptualization of the negative syndrome, was developed in part to address
      this inconsistency. The purpose of this study was (1) to replicate previous
      findings relating the deficit syndrome to impairment of certain kinds of
      attentional abilities, and (2) to compare the negative and deficit syndromes in
      their associations with performance on tests of attention. Data from 40
      individuals with schizophrenia were analyzed. Results provide evidence to suggest
      that impairment of certain attentional processes is associated with severity of
      deficit symptomatology, while impairment of other attentional processes is not.
      Moreover, the negative and deficit syndromes differed in their respective
      associations with attentional task performance at a trend level or above for five
      of seven tasks, suggesting that the negative and deficit syndromes do indeed have
      different underlying neuropsychological correlates.

PMID- 15954194
TI  - Age-at-first-registration for affective psychosis and schizophrenia.
AB  - We compared the age-at-first-registration for patients with schizophrenia and
      affective psychosis in a statewide mental health register. After excluding those
      receiving (1) a diagnosis of both schizophrenia (ICD-9 295.x) and affective
      psychosis (ICD-9 296.x), or (2) a diagnosis of ICD-9 296.1 (which can cover
      "major depressive episode"), we adjusted the distributions for the age structure
      of the background general population. We found that all distributions showed a
      wide age range of onset, with a similar male modal age group of 20-24 for
      schizophrenia and 25-29 for affective psychosis. The female modal age group was
      50-54 for both diagnoses. Although more individuals were diagnosed with
      schizophrenia (males = 2,434, females = 1,609) than with affective psychosis
      (males = 670, females = 913), the shape of the two distributions was similar.
      This finding suggests that factors influencing age-at-first-registration for
      schizophrenia and affective psychosis may be similar, especially for females.

PMID- 15954195
TI  - Five latent factors underlying schizophrenia: analysis and relationship to
      illnesses in relatives.
AB  - Clinical signs and symptoms in a sample of 1,043 individuals with schizophrenia
      or schizoaffective disorder were subjected to latent class factor analysis.
      Positive, negative, disorganized, and affective factors were similar in content
      to factors described in a number of other studies, while a fifth factor
      representing early onset/developmental signs provided a new area for
      investigation. The five sets of factor scores were logistically regressed on
      psychiatric illness indicators in first and second degree relatives. Relatives of
      probands with higher positive or negative symptom factor scores had a lower risk
      of depressive illness. Higher affective factor scores in probands predicted more
      mania and depression in relatives. Both the disorganized and the early
      onset/developmental factors were related to increased risk of psychiatric
      hospitalization in relatives, as well as increased risk of psychosis (marginally
      so for the disorganization factor). Increased early onset/developmental signs in
      the proband were also associated with increased risk for depression in relatives.
      These findings suggest a possible endophenotypic role for the factor scores in
      future studies.

PMID- 15954196
TI  - Developmental pathology, dopamine, and stress: a model for the age of onset of
      schizophrenia symptoms.
AB  - It is unknown why the onset of schizophrenia is typically during late adolescence
      or early adulthood. The fact that numerous brain maturational processes normally
      occur during this age period has led researchers to postulate how such processes
      may be related to the onset of symptoms. To help elucidate the question of age of
      onset, we selectively review schizophrenia-associated abnormalities of dopamine
      and related systems, including glutamate and hypothalamic-pituitary-adrenal
      systems; relevant models of pathophysiology; and the systems' developmental
      aspects. Based on current findings and conceptualizations, a model is then
      proposed in which, during adolescence, interactive pathological and normal
      adolescence-associated processes trigger a positive feedback system that results
      in a rapid increase in pathology that is proposed to underlie the development of
      active psychotic symptoms during late adolescence or early adulthood.

PMID- 15954197
TI  - Aggregability of red blood cells of schizophrenia patients with negative syndrome
      is selectively enhanced.
AB  - Schizophrenia patients can be categorized into positive and negative syndromes
      (PS and NS) by the behavioral criteria of the Positive and Negative Syndrome
      Scale (PANSS), but these symptoms can also be evaluated as a continuous trait.
      Both types exhibit cerebral microcirculatory disorders, which are ameliorated by
      drug treatment in PS but not in NS patients. Red blood cell (RBC) aggregability
      plays a major role in the microcirculation. Previously reported changes in RBC
      membrane phospholipid composition indicate a difference in aggregability between
      RBCs of NS and PS patients. In this study the aggregability of PS RBCs and NS
      RBCs was analyzed using a computerized cell flow-properties analyzer, as a
      physiological marker of NS and PS. Results showed that while the aggregability of
      PS RBCs was normal, that of NS RBCs was markedly enhanced and strongly correlated
      with the NS score. The results exhibited stability and reproducibility over 1 to
      8 weeks test-retest and were independent of gender, age at testing and onset of
      illness, fibrinogen levels, smoking, and current medication. NS RBCs have
      constitutively elevated aggregability, which can contribute to cerebral
      microcirculatory disorders and may be a biological marker for distinguishing
      between PS and NS in genetic studies of schizophrenia.

PMID- 15954198
TI  - Increased nitric oxide radicals in postmortem brain from patients with
      schizophrenia.
AB  - Alterations in antioxidant status in schizophrenia suggest free radical-mediated
      neurotoxicity; this finding can be a consequence of increased free radical
      production. There are multiple pathways to excess free radical generation and
      subsequent oxidative stress. One such pathway is the formation of peroxynitrite
      by a reaction of nitric oxide (NO) and superoxide radical. NO is formed from L
      arginine by nitric oxide synthase (NOS). A constitutive cytosolic isoform,
      neuronal NOS (nNOS), appears to be fairly stable in the postmortem brain tissues.
      Utilizing a sensitive fluorometric assay, NO levels were measured by its stable
      metabolites, nitrate and nitrite, in the caudate region of postmortem brain
      tissues from patients and control subjects. In the human brain, NO is metabolized
      primarily in the form of nitrate. A significantly increased level of NO was found
      in schizophrenia patients (241 +/- 146 pmol/mg dry weight, n = 18) than was found
      in those of normal (142 +/- 65 pmol/mg dry weight, n = 20) and psychiatric
      controls without schizophrenia (125 +/- 83 pmol/mg dry weight, n = 16) (analysis
      of covariance [ANCOVA], F = 6.446, df = 2,51, p = 0.003). These findings were
      independent of age, brain weight, postmortem interval (PMI), sample storage time,
      or cigarette smoking. Elevated NO levels in the brains of schizophrenia patients
      lend further support for the free radical pathology in schizophrenia.

PMID- 15954199
TI  - Caffeine intake in outpatients with schizophrenia.
AB  - Several studies suggest that caffeine intake is high in patients with
      schizophrenia and a few of them suggest that caffeine may contribute to
      schizophrenia symptomatology. None of these studies control for the effect of
      tobacco smoking, which is associated with induction of caffeine metabolism.
      Therefore, the high amount of caffeine intake among patients with schizophrenia
      may be due to their high prevalence of smoking. This is the first large study to
      explore whether caffeine intake in patients with schizophrenia is related to
      tobacco (or alcohol) use or to the severity of schizophrenia symptomatology. The
      sample included 250 consecutive consenting outpatients with a diagnosis of DSM-IV
      schizophrenia from Granada, Spain. Fifty-nine percent (147/250) of patients
      consumed caffeine. Current caffeine intake was associated with current smoking
      and alcohol use. As none of the females used alcohol, the association with
      alcohol was only present in males with schizophrenia. Among caffeine consumers,
      smoking was associated with the amount of caffeine intake. Cross-sectional
      schizophrenia symptomatology was not associated with caffeine intake.

PMID- 15954200
TI  - Alcohol consumption and the CAGE test in outpatients with schizophrenia or
      schizoaffective disorder and in the general population.
AB  - We conducted a survey of 151 outpatients with schizophrenia or schizoaffective
      disorder in Geneva, Switzerland, in 2000, and a mail survey in a representative
      sample of the general population of Geneva in 1996 (n = 742), to compare alcohol
      consumption and alcoholism in these two samples. Fewer patients with
      schizophrenia than participants in the general population drank alcohol daily
      (9.9% vs. 18.3%, p < 0.001). Excluding participants who said they currently never
      drank, alcohol consumption was similar in both groups (3 vs. 4 glasses/week, p =
      0.22). However, more patients with schizophrenia than participants in the
      population sample had a CAGE score > or = 2 (21.2% vs. 10.1%, p < 0.001),
      indicating a suspicion of alcoholism. Thus, asking about alcohol consumption
      produced different results from assessing hidden alcoholism with the CAGE. Either
      patients with schizophrenia under-reported their alcohol consumption, or the CAGE
      produced higher scores in these patients, for any given level of alcohol
      consumption. Previous research has shown, however, that the CAGE is a valid test
      in patients with schizophrenia, which suggests that in Geneva, alcoholism is more
      prevalent in patients with schizophrenia than in the general population.

PMID- 15954201
TI  - Sleep in untreated patients with schizophrenia: a meta-analysis.
AB  - The present meta-analysis investigated the characteristics of sleep in patients
      with schizophrenia without neuroleptic treatment at the time of sleep recording.
      The 20 selected studies included 652 participants (321 patients with
      schizophrenia and 331 healthy subjects). Effect sizes were evaluated using d
      values for the following sleep variables: sleep latency (SL), total sleep time
      (TST), sleep efficiency index (SEI), total awake time (TAT), stage 2 percentage
      (S2%), stage 4 percentage, slow-wave-sleep percentage, rapid-eye-movement (REM)
      percentage, and REM latency. The initial meta-analysis revealed that patients
      with schizophrenia have the following sleep disorders: increased SL, decreased
      TST, and decreased SEI. A moderator analysis revealed that these sleep disorders
      were worse for the neuroleptic-withdrawal group relative to the never-treated
      group. However, only never-treated patients showed significantly increased TAT
      and diminished S2%. These results confirm that patients with schizophrenia have
      sleep disorders that are not necessarily a consequence of neuroleptic treatments,
      suggesting that sleep disorders are an intrinsic feature of schizophrenia.
      However, it must be noted that some sleep disorders may be amplified by residual
      effects of neuroleptic withdrawal, while others appear to be dampened by
      neuroleptic treatment.

PMID- 15954203
TI  - At issue: A model for academic/industry collaboration.
AB  - Relationships between academia and industry are increasingly intimate and
      commercial. While opportunities are created for each partner, there are also
      important conflict of interest issues. Particularly challenging is ensuring that
      universities maintain their traditional role in public science while partnering
      with a commercial entity with a tradition of proprietary science. We describe a
      collaboration where the interests and values of each partner were articulated in
      advance and conflict of interest issues were resolved before legal and business
      arrangements were established in a contract. We discuss the principles involved
      and the resolutions achieved in the hope that it may provide a useful model for
      addressing academic/industry scientific collaborations.

PMID- 15954202
TI  - Current and future forecasts of service use and expenditures of Medicaid-eligible
      schizophrenia patients in the state of Georgia.
AB  - This study linked all claims data for reimbursable medical services and drugs of
      a cohort of 16,227 Medicaid-eligible recipients diagnosed with schizophrenia
      residing in the State of Georgia, with the treatment history file and Hospital
      Medical Information System file of each of the ten Georgia State psychiatric
      hospitals (Georgia Department of Human Resources [DHR]), which do not routinely
      bill Medicaid for services rendered. This provided a comprehensive picture of the
      medical resources consumed for each schizophrenia patient, allowing determination
      of expenditure use patterns, as well as forecast of future medical costs. Patient
      level data were aggregated by category of service and reported as costs per
      member per month (PMPM). Autoregressive integrated moving average time series
      models described the temporal pattern of expenditures for 8 years of total cost
      data and were used to forecast expenditures 5 years into the future. From 1990 to
      1997, total cumulative expenditures were over 1.09 billion dollars, expressed in
      1995 constant dollars. DHR institutional care dominated the cost of care, but
      expenditures significantly decreased over time. Apparently offsetting this
      decrease was an increase in prescription drug cost between 1990 and 1995, from
      5.7 percent of total expenditures to 10.5 percent. Total Medicaid and Medicare
      expenditures in 1995 dollars were relatively constant at approximately 700
      dollars PMPM. Prescription expenditures increased from 50 dollars in 1990 to 100
      dollars PMPM in 1997 and were projected to increase to 150 dollars in 2002.
      Expenditures were lower for persons continuously eligible for Medicaid than for
      the total cohort. Trends include a significant increase in prescription
      expenditures over time concurrent with decreases in inpatient expenditures and
      relatively stable changes in community mental health center expenditures.

PMID- 15954204
TI  - Measuring delusional ideation: the 21-item Peters et al. Delusions Inventory
      (PDI).
AB  - There is increasing evidence that in the general population there are schizotypal
      traits and symptoms that can be measured psychometrically. Norms are reported for
      a new 21-item version of the Peters et al. Delusions Inventory (PDI; Peters et
      al. 1999b). The PDI, originally based on the Present State Examination,
      incorporates the multidimensionality of delusions by including measures of
      distress, preoccupation, and conviction. A total of 444 healthy individuals
      completed the 21-item PDI and two other questionnaires measuring florid delusions
      and social desirability. A subsample also filled out an in-depth schizotypal
      personality scale. Thirty-three deluded inpatients also completed the PDI. The
      PDI's psychometric properties confirmed that it remains a reliable and valid
      instrument to measure delusional ideation in the general population. Consistent
      with the 40-item PDI, it was normally distributed, no sex differences were found,
      and there was an inverse relationship with age. Individual items were endorsed by
      just over one in four healthy adults. Although the deluded sample scored
      significantly higher, the range of scores overlapped considerably, with 11
      percent of healthy adults scoring higher than the mean of the deluded group. As
      with our previous findings, the two samples were differentiated by their ratings
      on the distress, preoccupation, and conviction scales. These results suggest that
      these dimensions may be more important than the content of belief alone for
      placing an individual on the continuum between normal and delusional thinking.

PMID- 15954205
TI  - Validation of polypharmacy process measures in inpatient schizophrenia care.
AB  - The influence of combining antipsychotics and different classes of psychotropic
      drugs on treatment outcome in schizophrenia remains unclear. As part of a
      comprehensive quality management program, we prospectively evaluated two
      schizophrenia polypharmacy performance measures in a cohort of 1,075
      consecutively recruited individuals with schizophrenia in seven psychiatric
      hospitals. Multiple concurrent antipsychotic and overall psychotropic
      polypharmacy rates were noticeably high. In case-mix-adjustment models
      controlling for a variety of confounding baseline parameters, patients discharged
      with more than one antipsychotic had significantly poorer outcomes with respect
      to both mental state and social functioning. Prescription of more than three
      psychotropic agents did not adversely affect social functioning when patients
      taking more than three were compared to patients given fewer medications. Case
      mix models suggest that antipsychotic polypharmacy, while used more often for
      individuals with chronic disease and more thought disturbance, is only partly a
      reaction to disease severity. The antipsychotic polypharmacy process measure may
      be used to identify treatment problems in order to find alternatives to
      polypharmacy. The measure can be easily assessed in a variety of settings and
      does not depend on the availability of case-mix data. The rising trend toward
      polypharmacy in schizophrenia care, which is not supported by current guideline
      recommendations, warrants critical appraisal.

PMID- 15954206
TI  - At issue: will the term brain disease reduce stigma and promote parity for mental
      illnesses?
AB  - The author questions both the scientific evidence and potential effect of the
      current trend to change the language used to describe certain serious mental
      illnesses (schizophrenia, schizoaffective disorder, or bipolar affective
      disorder) to "brain diseases." It is argued that changing nomenclature will not
      be effective in reducing stigma unless the treatment and financial circumstances
      of the seriously mentally ill are improved. Finally, it is suggested that we need
      to expand our understanding and treatment of "physical illnesses" to encompass
      the social and psychological dimensions, not narrow our view of psychiatric
      illnesses.

PMID- 15954207
TI  - The stereotype of schizophrenia and its impact on discrimination against people
      with schizophrenia: results from a representative survey in Germany.
AB  - This study aims at assessing the prevalence of different components of the
      stereotype of schizophrenia among the general public and examining their impact
      on the preference for social distance and the acceptance of structural
      discrimination--that is, imbalances and injustices inherent in legal regulations
      and the provision of health care. In spring 2001, a representative survey was
      carried out in Germany involving individuals of German nationality aged 18 years
      and older and living in noninstitutional settings (n = 5,025). A personal, fully
      structured interview was conducted, including a list of items covering the
      various aspects of the stereotype, a social distance scale, and items assessing
      respondents' agreement with structural discrimination. Among the five stereotype
      components, the perception of people with schizophrenia as being unpredictable
      and incompetent was most frequently endorsed by the public, followed by perceived
      dangerousness. While the desire for social distance was best predicted by these
      two stereotype components, holding the individual responsible for the illness was
      the most powerful predictor of the acceptance of structural discrimination.

PMID- 15954209
TI  - Private sector, lawmakers push for Health I.T. reform.

PMID- 15954208
TI  - First person account: My dream life, a normal life.

PMID- 15954210
TI  - Umbilical cord clamping in preterm infants.

PMID- 15954211
TI  - [Non-manifested stages of schizophrenia: psychopathology and therapy].
AB  - Presented is a hypothesis that allows to interpret non-manifested stages of
      schizophrenia: prodromes and remissions characterized negative schizophrenia and
      reflected a slow progress of the endogenous process; formation of residual states
      indicated a change of stereotypy of development of the disease with attenuation
      of its destructive tendencies and transition to evolution, comparable to
      personality disorders dynamics. Using clinically differentiated models (the
      dimensional model of schizophrenia and model of personality disorders dynamics),
      the arguments for the hypothesis are presented. According to this hypothesis, a
      dual-purpose psychopharmacotherapeutic model appears to be an optimal strategy.
      One of the therapeutic aims is arrest of psychosis; the other is preventing, or
      at least delaying, manifestation or next exacerbation of positive disorders and
      slowing down the disease progression in the non-psychotic stages.

PMID- 15954212
TI  - [Some indices of congenital and acquired immunity in patients with endogenous
      diseases of schizophrenic spectrum disorders].
AB  - Indices of congenital leukocyte elastase (LE) activity and adaptive immunity (a
      level of autoantiboies to nerve growth factor--AabNGF) in blood serum of patients
      with schizophrenia (attack-like, continuous and slow progressive types) and
      schizoaffective psychosis have been compared with clinical presentations of the
      disorders. A patient's state was assessed by clinico-psychopathological methods
      and with the Positive and Negative Syndromes Scale (PANSS). All schizophrenia
      types and schizoaffective psychosis were accompanied by LE activity elevation. An
      increase of AabNGF level was observed only in attack like and continuous
      schizophrenia. Correlations between AabNGF level and negative symptoms evaluated,
      using the PANSS, suggest a relation of autoimmune reactions against NGF to the
      progression of schizophrenic process. Differences in AabNGF level between
      schizoaffective psychosis and attack-like schizophrenia confirm nosologic
      independence of schizoaffective psychosis and demand for additional differential
      laboratory diagnosis of these disorders.

PMID- 15954213
TI  - [The 60th anniversary of Institute of Neurology of Russian Academy of Medical
      Sciences].

PMID- 15954214
TI  - ["Off-label-use"].

PMID- 15954215
TI  - Stumbling around in the dark.

PMID- 15954216
TI  - Patient choice in clinical trials.

PMID- 15954217
TI  - AMREF: good news for Africa.

PMID- 15954218
TI  - Latin America's urbanisation is boosting obesity.

PMID- 15954219
TI  - Aid workers warn of North Korea's forgotten health crisis.

PMID- 15954220
TI  - China rejects internet claims of human cases.

PMID- 15954221
TI  - Concentration and particle size of airborne toxic algae (brevetoxin) derived from
      ocean red tide events.
AB  - Red tides in the Gulf of Mexico are formed by blooms of the dinoflagellate
      Karenia brevis, which produces brevetoxins (PbTx). Brevetoxins can be transferred
      from water to air in the wind-powered whitecapped waves during red tide episodes.
      Inhalation exposure to marine aerosol containing PbTx causes respiratory
      problems. A liquid chromatograph/ tandem mass spectrometric method was developed
      for the detection and quantitation of several PbTxs in ambient samples collected
      during red tide events. This method was complemented by a previously developed
      antibody assay that analyzes the entire class of PbTx compounds. The method
      showed good linearity, accuracy, and reproducibility, allowing quantitation of
      PbTx compounds in the 10 pg/m3 range. Air concentrations of PbTxs and brevenal
      for individual samples ranged from 0.01 to 80 ng/m3. The particle size showed a
      single mode with a mass median diameter between 6 and 10 microm, which was
      consistent for all of the PbTx species that were measured. Our results imply that
      individual PbTxs were from the same marine aerosol or from marine aerosol that
      was produced from the same process. The particle size indicated the likelihood of
      high deposition efficiency in the respiratory tract with the majority of aerosol
      deposited in the upper airways and small but not insignificant deposition in the
      lower airways.

PMID- 15954222
TI  - Polybrominated diphenyl ethers in the sediments of the Great Lakes. 2. Lakes
      Michigan and Huron.
AB  - Sediment cores were taken in 2002 in Lakes Michigan and Huron at six locations. A
      total of 75 samples were characterized, dated using 210Pb, and analyzed for 10
      congeners of polybromodiphenyl ether (PBDE) including BDE209, as well as 39
      congeners of polychlorinated biphenyls (PCBs). The concentrations of nine tri-
      through hepta-BDE congeners (Sigma9PBDE) in the surficial sediments range from
      1.7 to 4 ng g(-1) for Lake Michigan and from 1.0 to 1.9 ng g(-1) for Lake Huron,
      on the basis of the dry sediment weight. The Sigma9PBDEs fluxes to the sediment
      around the year 2002 are from 36 to 109 pg cm(-2) yr(-1) in Lake Michigan and
      from 30 to 73 pg cm(-2) yr(-1) in Lake Huron, with spatial variations in both
      lakes. The flux of BDE209 ranges from 0.64 to 2.04 ng cm(-2) yr(-1) and from 0.67
      to 1.41 ng cm(-2) yr(-1) in Lake Michigan and Lake Huron, respectively. Dramatic
      increases in PBDE concentrations and fluxes upward toward the sediment surface
      and the present time are evident at all locations. The inventory of PBDEs in both
      lakes appears to be dependent upon latitude and the proximity to populated areas,
      implying that north-bound air plumes from urban areas are the major sources of
      PBDEs found in the lake sediments at locations away from the shores. Heavier
      congeners are more abundant in the sediments than in air and fish samples in the
      region. BDE209 is about 96% and 91% of the total PBDEs on a mass basis in Lake
      Michigan and Lake Huron, respectively; both are higher than the 89% found in Lake
      Superior, although a t test shows that the value for Lake Huron is not
      statistically different from that for Lake Superior at the 95% confidence level.

PMID- 15954223
TI  - Environmental stresses and skeletal deformities in fish from the Willamette
      River, Oregon.
AB  - The Willamette River, one of 14 American Heritage Rivers, flows through the most
      densely populated and agriculturally productive region of Oregon. Previous
      biological monitoring of the Willamette River detected elevated frequencies of
      skeletal deformities in fish from certain areas of the lower (Newberg pool [NP],
      rivermile [RM] 26 - 55) and middle (Wheatland Ferry [WF], RM 72 - 74) river,
      relative to those in the upper river (Corvallis [CV], RM 125-138). The objective
      of this study was to determine the likely cause of these skeletal deformities. In
      2002 and 2003, deformity loads in Willamette River fishes were 2-3 times greater
      at the NP and WF locations than at the CV location. There were some differences
      in water quality parameters between the NP and CV sites, but they did not readily
      explain the difference in deformity loads. Concentrations of bioavailable metals
      were below detection limits (0.6 - 1 microg/ L). Concentrations of bioavailable
      polychlorinated biphenyls (PCBs) and chlorinated pesticides were generally below
      0.25 ng/L. Concentrations of bioavailable polycyclic aromatic hydrocarbons were
      generally less than 5 ng/L. Concentrations of most persistent organic pollutants
      were below detection limits in ovary/oocyte tissue samples and sediments, and
      those that were detected were not significantly different among sites. Bioassay
      of Willamette River water extracts provided no evidence that unidentified
      compounds or the complex mixture of compounds present in the extracts could
      induce skeletal deformities in cyprinid fish. However, metacercariae of a
      digenean trematode were directly associated with a large percentage of
      deformities detected in two Willamette River fishes, and similar deformities were
      reproduced in laboratoryfathead minnows exposed to cercariae extracted from
      Willamette River snails. Thus, the weight of evidence suggests that parasitic
      infection, not chemical contaminants, was the primary cause of skeletal
      deformities observed in Willamette River fish.

PMID- 15954224
TI  - Congener-specific tissue distribution of aroclor 1254 and a highly chlorinated
      environmental PCB mixture in rats.
AB  - Polychlorinated biphenyl (PCB) mixtures were synthesized and marketed in Eastern
      European countries, but little is known abouttheir composition, distribution,
      ortoxicity. PCB-contaminated soil from the former production site of the Polish
      PCB mixture Chlorofen was collected, and the PCBs were extracted. An in vivo
      study was performed to investigate the PCB tissue distribution and biochemical
      effects of this soil extract in immature male Sprague-Dawley rats. Rats were
      administered 0.05 mmol/kg soil-extracted PCBs or Aroclor 1254 and sacrificed 7
      days later, and congener-specific PCB profiles in selected tissues were
      determined. Distribution of SigmaPCBs (sum of 120 congeners) in tissues was
      primarily a function of lipid content of the tissues, except for the spleen,
      which retained more PCB than other tissues. Multivariate analysis of the PCB
      congener data showed that (a) congener profiles in tissues had changed, as
      compared to the parent mixture; (b) disposition and redistribution of individual
      congeners in vivo differed between both mixtures; and (c) more highly chlorinated
      congeners were retained in the spleens of both treatment groups. Differences in
      the induction of cytochrome P-450 1A and 2B subfamilies reflected the homologue
      composition of the respective mixtures and predict a different toxicity profile
      for Chlorofen than for Aroclor 1254.

PMID- 15954225
TI  - Photochemical transformations of benzo[e]pyrene in solution and adsorbed on
      silica gel and alumina surfaces.
AB  - The photodegradation of benzo[e]pyrene (BeP), a ubiquitous polycyclic aromatic
      hydrocarbon (PAH) contaminant, was investigated in solution and adsorbed on
      surfaces modeling the atmospheric particulate matter to provide fundamental
      information that could help to clarify its fate in the atmosphere. Diones, diols,
      and hydroxy derivatives were identified as the major photoproducts of BeP
      irradiated under simulated atmospheric conditions. The relative distribution of
      the products and the photodegradation rates of BeP were affected by the average
      pore size of the surface. Major photoproducts characterized in samples adsorbed
      on silica gel and alumina surfaces were not observed in irradiated solutions of
      BeP in hexane. In acetonitrile, the photodegradation rate was faster than in
      hexane, and one of the diones was observed. Different photoreaction pathways seem
      to take place in polar versus nonpolar microenvironments.

PMID- 15954226
TI  - Percutaneous absorption of 4-cyanophenol from freshly contaminated soil in vitro:
      effects of soil loading and contamination concentration.
AB  - Despite the skin's excellent barrier function, dermal exposure to soil
      contaminated with toxic chemicals can represent a significant health hazard
      (e.g., via multiple work related contacts in the farming and waste disposal
      industries). The development of environmental standards or limits for chemical
      levels in soil has been impeded because quantification of percutaneous uptake
      from this medium has not been well-defined. The objective of the research
      described here, therefore, was to better characterize the rate and extent of
      dermal penetration as a function of soil loading and degree of soil
      contamination. The absorption of a model compound (4-cyanophenol, CP) across
      hairless mouse skin in vitro has been determined at four different soil loadings
      (5, 11, 38 and 148 mg cm-2) and at six levels of soil contamination
      (concentrations ranging from 0.19 to 38 mg/g soil). Following 8 h of exposure,
      the amount of CP absorbed was independent of soil loading when CP concentration
      was constant, implying that the quantity of soil presentwas always sufficientto
      provide atleast a single layer of tightly packed particles. At the lowest
      loadings, however, with increasing times of exposure, the CP transport rate fell
      off due to depletion of chemical from the soil. At constant soil loading (38 mg
      cm(-2)), CP flux (Jss) across the skin was linearly proportional to the level of
      contamination (C(o)soil) over the range 0.19 to 23.5 mg of CP per gram of soil:
      Jss (micorg cm(-2) h(-1)) = (1.1 x 10(-5) g cm(-2) h(-1)) x Csoil (microg/g
      soil). At the highest CP contamination concentration, however, the transport rate
      was about an order of magnitude higher than expected, possibly due to the
      presence of pure CP crystals. In conclusion, these results provide new
      quantifications of the characteristics of dermal uptake from chemically
      contaminated soils and important information with which to develop and verify
      predictive models of dermal absorption.

PMID- 15954227
TI  - Seladin-1 as a target of estrogen receptor activation in the brain: a new gene
      for a rather old story?
AB  - Experimental evidence indicates that estrogen exerts neuroprotective effects.
      According to the fact that Alzheimer's disease (AD) is more common in post
      menopausal women, estrogen treatment has been proposed. However, the beneficial
      effect of estrogen or selective estrogen receptor modulators (SERMs) in
      preventing or treating AD is a controversial issue, which will be summarized in
      this review. Recently, a novel gene, named selective AD indicator-1 (seladin-1),
      has been isolated and found to be down-regulated in brain regions affected by AD.
      Seladin-1, which is considered the human homolog of the plant protein
      DIMINUTO/DWARF1, confers protection against beta-amyloid-mediated toxicity and
      from oxidative stress and is an effective inhibitor of caspase 3 activity, a key
      mediator of apoptosis. This review will present the up-to-date findings regarding
      seladin-1 and DIMINUTO/DWARF1. In addition, the possibility that seladin-1 may be
      a downstream effector of estrogen receptor activation in the brain, based on our
      recent experimental findings using a human fetal neuronal model, will be
      addressed.

PMID- 15954228
TI  - Declining fertility in the lethal yellow mouse is related to progressive
      hyperleptinemia and leptin resistance.
AB  - Mice possessing the lethal yellow mutation (C57BL/6J A(y)/a) become obese and
      develop hyperleptinemia and leptin resistance as they age. To determine the
      relationship between altered leptin physiology and reproductive function in these
      mice, we compared body weight (BW), serum leptin concentration, ovulation rate,
      and in vitro blastocyst development among 120- and 180-d-old lethal yellow and
      black non-mutant (a/a) mice. Estrous female yellow and black mice were mated with
      fertile black males. Oviducts were flushed approximately 36 h after mating and
      the recovered embryos were cultured for 96 h. BW, serum leptin levels, and the
      leptin:BW ratio differed among groups as follows: 180-d yellow > 120-d yellow >
      180-d black = 120-d black. Ovulation rate was similar among 120-d yellow and
      black, and 180-d black mice. Among 180-d yellow mice, five of twelve mice failed
      to ovulate, but the other seven mice ovulated a similar number of oocytes as
      their black counterparts (8.4 +/- 0.9 versus 8.0 +/- 1.3). Non-ovulators had
      higher (P < 0.05) leptin levels (56.6 +/- 1.8 ng x mL(-1)) than ovulators (46.2
      +/- 3.5), but BW did not differ significantly. Fewer embryos from 180-d yellow
      mice reached the blastocyst stage in culture than did the embryos from black mice
      (55% versus 83%, P < 0.05). Moreover, blastocyst development in 180-d old yellow
      mice negatively correlated with leptin levels (r = -0.797, P = 0.032) and
      leptin:BW ratio (r = -0.847, P = 0.016), but not with BW. Declining reproductive
      function in lethal yellow mice appears to be related to increasing levels of
      leptin and progression of leptin resistance.

PMID- 15954229
TI  - Ovarian effects of a high lactose diet in the female rat.
AB  - Young women with galactosemia experience ovarian failure at a very early age
      raising concern about the ovarian toxicity of galactose. While galactose may be
      present in the diet as a monosaccharide, it is predominantly derived from
      cleavage of the disaccharide lactose within the intestine. Our previous studies
      in animals have shown that high galactose diets inhibit ovarian follicular
      development and long-term exposure to high lactose diets retards growth of rats.
      The objective of the present study was to determine whether galactose exposure in
      the form of dietary lactose mimics the effects found previously with diets rich
      in galactose. Sixty female Long-Evans rats (25-day-old) were randomly assigned to
      two groups and fed a control diet (41.9% glucose in AIN93G [American Institute of
      Nutrition], CON) before lactose treatment. Unilateral ovariectomy (uOVX) was
      performed on half of the rats in each group to determine baseline ovarian
      follicle numbers. The study diet was a high lactose diet (HLD) containing 41.9%
      lactose in AIN93G. Study diet exposure started 1 month after uOVX (3 months old)
      and continued for 7 months in the treatment group. The control group remained on
      the 41.9% glucose diet throughout. Vaginal cytology, ovarian morphometric
      analyses, and serum concentrations of estradiol and progesterone were examined.
      Long-term exposure to the HLD decreased the body weights of animals and
      progesterone concentrations in the serum but produced no harmful effects on
      ovarian morphology or function. Beginning at 5 months of age (two months of
      lactose treatment) increasing numbers of females began to cycle irregularly but
      there was no difference between the glucose and lactose diet groups. These
      negative findings imply that administration of galactose in the form of lactose
      seems to be much less toxic than when galactose is fed to animals. From a human
      health perspective, these results are somewhat reassuring, since in general,
      women eat lactose-containing foods rather than foods that contain large amounts
      of free galactose.

PMID- 15954230
TI  - [A study on the module using pendulum combined with straight wire appliance in
      Angle class II and skeletal class I malocclusion].
AB  - OBJECTIVE: To investigate morphologic changes of Angle class II and skeletal
      class I patients during pendulum and straight wire appliances treatment and to
      analyze the mechanism of this treatment protocol. METHODS: 10 patients with Angle
      class II and skeletal class I malocclusion were recruited. The lateral
      cephalometric radiographs were evaluated to determine if there were significant
      differences among pre-treatment (T1), after molar distalization (T2), and post
      treatment (T3) variables including skeletal, dental and soft tissue
      relationships. RESULTS: Differences between the T1 and T2 means were significant
      for distal movement and distal angulation of the maxillary molars (P < 0.01),
      mesial angulation of the maxillary incisors (P < 0.05), mesial movement of the
      maxilla (P < 0.01) . There were no significant changes between T1 and T3 in
      respect saggital position and angulation of the maxillary molars (P > 0.05) .
      Only the mesial movement of lower first molars and upper and lower jaws were
      significant (P < 0.01) during the whole treatment. No upper second molar
      impaction was detected after treatment. CONCLUSION: The upper molars
      distalization could be achieved by pendulum appliance. The class I molar
      relationship could be obtained by the differential growth of jaws and the
      differential movement of upper and lower molars.

PMID- 15954231
TI  - [Regional meeting of the Japanese Society of Otolaryngology. Japan.  22003-2004.
      Abstracts].

PMID- 15954233
TI  - Findings of scientific misconduct.

PMID- 15954232
TI  - [The 47th annual meeting of the Japanese Society of Child Neurology. Kumamoto,
      Japan. May 19-21, 2005. Program and Abstracts].

PMID- 15954234
TI  - The Bariatric Quality of Life index: a measure of well-being in obesity surgery
      patients.
AB  - BACKGROUND: Quality of life (QoL) is considered to be the true measure for the
      effectiveness of a surgical procedure, but there are only a few validated
      instruments available for bariatric surgery. Therefore, a new diseasespecific 30
      item instrument was created, which was called Bariatric Quality of Life (BQL)
      questionnaire. METHODS: To validate the BQL, we studied 133 patients after 4
      different types of bariatric surgery. Initially, mean body mass index (BMI) was
      47.2 +/-7.6 kg/m2 and mean age was 38.8 +/-11.0 years. At baseline, and 1, 6, and
      12 months after surgery, patients filled in the BQL, the SF-12 (Short Form of SF
      36 Health Survey), the GIQLI (Gastrointestinal Quality of Life Index), and the
      BAROS (Bariatric Analysis and Reporting Outcome System). RESULTS: Internal
      consistency of the BQL was found to be good, with Cronbach's alpha ranging
      between 0.71 and 0.86. Factor analyses suggested that the BQL included a highly
      consistent set of QoL items and a second part on co-morbidities and
      gastrointestinal symptoms. At the 12 months follow-up, the BQL was closely
      correlated to SF 12 (Pearson's r = 0.86), GIQLI (0.68), BAROS (0.71), and excess
      weight loss (0.55). Standardized effect sizes over time were larger for the BQL
      (1.39 and 1.58) than for the other instruments. CONCLUSIONS: The BQL
      questionnaire is a validated instrument ready for clinical use.

PMID- 15954236
TI  - Chronic constrictive pericarditis: is tuberculosis still a cause?

PMID- 15954235
TI  - Prospective audit of the quality of ENT emergency clinic notes before and after
      introduction of a computerized template.
AB  - This study evaluated the accuracy of notes in an ENT urgent referral clinic,
      based on a standard of note keeping established within the trust. The results
      initially failed to meet the set standard and a change of practice was initiated
      by introduction of a computerized template that allowed for easier and more
      accurate data entry. After re-evaluation, the notes were found to be accurate and
      to contain relevant demographic data in more than 90 per cent of cases.

PMID- 15954237
TI  - Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of
      Thrombosis and Haemostasis.

PMID- 15954238
TI  - Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of
      Thrombosis and Haemostasis.

PMID- 15954239
TI  - Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of
      Thrombosis and Haemostasis.

PMID- 15954240
TI  - Vitamin E and Health. Proceedings of a conference, May 22-24, 2004, Boston,
      Massachusetts, USA.

PMID- 15954241
TI  - Child neurology: workforce and practice characteristics.
AB  - For more than a decade, reports have indicated that the supply of child
      neurologists is inadequate to provide care for the growing number of children
      with acquired and genetic neurological conditions. It is critical to understand
      how the shortages affect the practice of child neurology, the attitudes of child
      neurologists, and ability of the field to attract new members. This Issue Brief
      examines these workforce issues, and profiles the attitudes and practice
      characteristics of child neurologists and trainees.

PMID- 15954242
TI  - Staying ahead of the feds: EPA proposes cap-and-trade to cut back on mercury
      emissions, but many states think they have a quicker, better solution.

PMID- 15954243
TI  - Managed care: in it for the long term. Using managed care for Medicaid long-term
      care is once again getting states' attention.

PMID- 15954244
TI  - Determination of microbial volatile organic compounds adsorbed on house dust
      particles and gypsum board using SPME/GC-MS.
AB  - Adsorption of microbial volatile organic compounds (MVOCs) on house dust was
      analyzed by performing solid phase microextraction (SPME) in combination with gas
      chromatography-mass spectrometry (GC-MS). Settled dust samples were exposed to
      five selected MVOCs and to cultures of the molds Stachybotrus chartarum,
      Aspergillus versicolor, and Chaetomium globosum. Considerable desorption of the
      MVOCs adsorbed on the dust occurred spontaneously within a few hours at room
      temperature and within several days or weeks after storage at -20 degrees or -80
      degrees C. Similar results were found for a sample of a gypsum board cultivated
      with A. versicolor. SPME/GC-MS analysis performed immediately after sampling
      revealed several of the studied MVOCs on gypsum board and settled dust collected
      in a house garage with visible mold growth. MVOCs adsorbed on respirable
      particles of house dust can be inhaled and reach deep into the respiratory
      system, which may partly explain health effects that have been found to be
      associated with the presence of low concentrations of MVOCs in air. Particle
      bound MVOCs can easily be detected by SPME/GC-MS analysis, thus this technique
      may prove to be very useful in indoor air research for identifying factors that
      affect human health. PRACTICAL IMPLICATIONS: We used SPME combined with GC-MS to
      study the adsorption and desorption of MVOCs on house dust particles that had
      been exposed to cultivated molds and molds in a damp building. Adsorbed MVOCs
      desorb spontaneously but this process can be slowed down by storing samples at 
      20 degrees or -80 degrees C. This opens up a possibility to apply SPME/GC-MS to
      reveal mold growth in buildings and to determine MVOCs in respirable dust
      particles that may reach deep in the respiratory system and lead to respiratory
      illnesses.

PMID- 15954245
TI  - The poor state of health care quality in the U.S.: is malpractice liability part
      of the problem or part of the solution?

PMID- 15954246
TI  - Retaining versus removing natural teeth.

PMID- 15954247
TI  - The in vitro performance of laser fluorescence and caries-detector dye for
      detecting residual carious dentin during tooth preparation.
AB  - OBJECTIVE: The aim of this in vitro study was to compare the performance of a
      laser fluorescence device (DIAGNOdent) and a caries-detector dye for detecting
      residual dentinal caries. METHODS AND MATERIALS: Forty extracted human molar
      teeth with deep dentinal carious lesions on their approximal surfaces were used
      for the study. The caries were removed by a new chemomechanical system, Carisolv.
      Three independent observers checked all cavities for residual caries using caries
      detector dye and DIAGNOdent. The presence or absence of residual caries was
      verified using polarized light microscopy as the gold standard. Three observers
      recorded two different measurements at the same site after 2 weeks to determine
      intra- and interexaminer reproducibility of the DIAGNOdent. RESULTS: Average
      kappa values of 0.61 for interexaminer reproducibility and 0.94 for intraexaminer
      reproducibility were determined. The specificity of caries-detector dye was found
      to be 100% and the specificity of the DIAGNOdent was 86%. CONCLUSION: Although
      DIAGNOdent showed greater sensitivity than caries-detector dye (P < .05), low
      sensitivity values for each diagnostic system may lead to teeth with residual
      caries being undetected. Therefore, it might be advisable to reconsider the
      criteria for detecting residual caries during tooth preparation.

PMID- 15954248
TI  - Cervical lymphadenopathy in the dental patient: a review of clinical approach.
AB  - Lymph node enlargement may be an incidental finding on examination, or may be
      associated with a patient complaint. It is likely that over half of all patients
      examined each day may have enlarged lymph nodes in the head and neck region.
      There are no written guidelines specifying when further evaluation of
      lymphadenopathy is necessary. With such a high frequency of occurrence, oral
      health care providers need to be able to determine when lymphadenopathy should be
      investigated further. Although most cervical lymphadenopathy is the result of a
      benign infectious etiology, clinicians should search for a precipitating cause
      and examine other nodal locations to exclude generalized lymphadenopathy. Lymph
      nodes larger than 1 cm in diameter are generally considered abnormal. Malignancy
      should be considered when palpable lymph nodes are identified in the
      supraclavicular region, or when nodes are rock hard, rubbery, or fixed in
      consistency. Patients with unexplained localized cervical lymphadenopathy
      presenting with a benign clinical picture should be observed for a 2- to 4-week
      period. Generalized lymphadenopathy should prompt further clinical investigation.
      This article reviews common causes of lymphadenopathy, and presents a methodical
      clinical approach to a patient with cervical lymphadenopathy.

PMID- 15954249
TI  - Management of hypodontia: restorative considerations. Part III.
AB  - This paper, the third in the series, initially details the role of the
      restorative dentist in treating patients with hypodontia. (See Quintessence Int
      2005;36:263-270 and 345-353 for the first two papers.) A range of treatment
      options, including implants, adhesive techniques, and removable prostheses, are
      covered. The investigators have detailed the clinical indications, and noted
      their relative advantages and disadvantages.

PMID- 15954250
TI  - Subgingival debridement with a teflon-coated sonic scaler insert in comparison to
      conventional instruments and assessment of substance removal on extracted teeth.
AB  - OBJECTIVE: Previous studies have shown that endotoxins are located on the
      periodontally diseased root cementum and not within it. To what extent a Teflon
      tubed sonic scaler was capable of removing bacterial deposits in comparison to
      conventional scaling instruments, and the resulting root surface roughness and
      root surface topography, were recently assessed. The objective of the present
      study was to evaluate how much root cementum is removed with these instruments.
      METHODS AND MATERIALS: Eighty-two teeth were treated subgingivally on one
      approximal site either with a Teflon-coated sonic scaler insert (tSS), a Gracey
      curette, a conventional sonic scaler (SS), a piezoelectric ultrasonic scaler
      insert (US), or an oscillating Periotor insert (PT) before extraction. The
      untreated site served as control. The width and length of cementum removal were
      compared histomorphometrically. Nonparametric analyses were carried out for
      statistical comparison. RESULTS: The US, PT, and tSS inserts removed less
      substance than the curettes or SS inserts. The cementum removed was 40 microm for
      root surfaces treated with the curette or SS, 30 microm for those treated with
      US, 20 microm for PT, and 17 microm for tSS. CONCLUSION: The Teflon-coated sonic
      scaler inserts can be a reasonable choice for gentle maintenance treatment of
      compliant patients with good plaque control, and little or no subgingival
      deposits.

PMID- 15954251
TI  - Dental caries and obesity in children: different problems, related causes.

PMID- 15954252
TI  - Thickness and stiffness characteristics of custom-made mouthguard materials.
AB  - OBJECTIVES: The purpose of this investigation was to determine the thickness of
      different types of custom-made mouthguards after processing and the deformational
      changes after simulated occlusal loading. MATERIALS AND METHODS: Ten mouthguards
      were fabricated for the same dental arch using the following materials and
      processing techniques: Group I: vacuum-formed (4 mm), Colored Mouthguard; Group
      II: vacuum-formed (4 mm), Proform; and Group III: pressure-laminated (3 + 3 mm),
      Drufosoft. After processing, the thickness was measured in three places: lingual
      cusps of the first molar, distal marginal ridge of the first premolar; and facial
      of central incisor. The stiffness of each group was determined by applying a
      simulated clenching force to the first molar lingual cusp areas on an Instron
      test machine with a blunt probe. The corresponding penetration was measured with
      a dial gauge. Thickness and force-deflection measurements of the different
      mouthguard groups were compared using analysis of variance and post hoc tests.
      RESULTS: The mean thicknesses at the molar for Groups I and II were 1.55 and 1.52
      mm, respectively, and were significantly smaller then the corresponding thickness
      for Group III (3.48 mm). The mean thicknesses at the facial of the incisors for
      Groups I and II were similar (2.05 and 2.06 mm, respectively), and were
      significantly smaller than the corresponding thickness for Group III (3.29 mm).
      Groups I and II demonstrated similar stiffness that was significantly higher than
      that for Group III. CONCLUSION: These results show that vacuum-formed mouthguards
      produced smaller thicknesses than the pressure-laminated mouthguards. The
      pressure-laminated mouthguards produced material thicknesses that were previously
      shown to be adequate to protect athletes from trauma.

PMID- 15954254
TI  - Glycemic control in patients with diabetes mellitus upon admission to a dental
      clinic: considerations for dental management.
AB  - OBJECTIVE: The purpose of this study was to determine the level of glycemic
      control in dental patients with diabetes upon admission to a dental school
      clinic. METHODS AND MATERIALS: One hundred patients (mean age: 57.7 years) of the
      Oral Diagnosis-Admissions Clinic at the University of Minnesota School of
      Dentistry, Minneapolis, Minnesota, with diabetes mellitus were chosen as
      subjects. Fasting blood glucose was measured using a portable blood glucose
      monitoring device as a part of their initial dental examination. RESULTS: Twenty
      eight of the 100 patients were found to be hyperglycemic (> or = 126 mg/dl; 174.8
      +/- 40.8 mg/dl; mean +/- SEM); 2 patients were found to be hypoglycemic (< 70
      mg/dl). Of the 8 patients with type 1 diabetes in the cohort, 3 (37.5%) were very
      hyperglycemic, with fasting blood glucose levels > 250 mg/dl. CONCLUSIONS: This
      is important information for dental practitioners because patients with diabetes
      may not be under good glycemic control, and dentists may have to take special
      precautions before, during, and after treatment. This paper reviews the
      pathogenesis of diabetes, the detection of patients with undiagnosed or poorly
      controlled diabetes, and the management of patients with diabetes during dental
      treatment.

PMID- 15954253
TI  - In vitro cariostatic effect of whitening toothpastes in human dental enamel
      microhardness evaluation.
AB  - OBJECTIVE: The aim of this study was to evaluate, in vitro, the cariostatic
      effect of whitening toothpastes. METHODS AND MATERIALS: Ninety-five dental
      fragments were obtained from nonerupted third molars. The fragments were embedded
      in polystyrene resin and sequentially polished with abrasive papers (400-, 600-,
      and 1,000-grit) and diamond pastes of 6, 3, and 1 microm. The fragments were
      assigned in five groups according to toothpaste treatment: G1 = Rembrandt Plus
      with Peroxide; G2 = Crest Dual Action Whitening; G3 = Aquafresh Whitening Triple
      Protection; and the control groups: G4 = Sensodyne Original (without fluoride);
      G5 = Sensodyne Sodium Bicarbonated (with fluoride). The initial enamel
      microhardness evaluations were done. For 2 weeks the fragments were submitted
      daily to a de-remineralization cycle followed by a 10-minute toothpaste slurry.
      After that, the final microhardness tests were done. The percentage of mineral
      loss of enamel was determined for statistical analysis. Analysis of variance and
      the Tukey test were applied. RESULTS: The results did not show statistically
      significant differences in mineral loss among groups G1, G2, G3, and G5, which
      statistically differ from G4 (toothpaste without fluoride). G4 showed the highest
      mineral loss (P < or = .05). CONCLUSION: The whitening toothpastes evaluated
      showed a cariostatic effect similar to regular, nonwhitening toothpaste.

PMID- 15954255
TI  - Hemifacial hyperplasia: a case report.
AB  - Hemifacial hyperplasia is a developmental disorder characterized by a marked
      unilateral asymmetry. The etiology is unknown, although several factors have been
      described. It involves not only the hard tissues of the face, but the soft
      tissues as well. A case report of an adult woman with hemifacial hyperplasia
      highlighting the clinical significance is presented.

PMID- 15954256
TI  - Dentigerous cyst associated with an impacted mandibular third molar.

PMID- 15954257
TI  - Probabilistic environmental risk assessment.

PMID- 15954258
TI  - Screening for the presence of estrogenic compounds and polycyclic aromatic
      hydrocarbons in experimental flue gas matrices.

PMID- 15954259
TI  - Engineering disease resistance in plants using the CF9-AVR9 two component system.

PMID- 15954260
TI  - Computer assisted track analysis of nuclear migration in living root hairs.

PMID- 15954261
TI  - Application of accelerated aging test to compare winter wheat seed vigour.

PMID- 15954262
TI  - The influence of adjuvants on flat fan spray nozzles.

PMID- 15954263
TI  - Synthesis of trans-4-aryl-3-(omega-chloroalkyl) -2-azetidinones.

PMID- 15954264
TI  - Quality determination on juveniles sole (Solea senegalensis), reared with non
      protein energy diets.

PMID- 15954265
TI  - Multifunctionality in agriculture: supply of and demand for landscape amenities.

PMID- 15954266
TI  - Prevalence of malnutrition and anaemia among infants aged 4 - 12 months in Kilosa
      district-rural Tanzania.

PMID- 15954267
TI  - Ploidy and colour pattern coincide in azalea bicoloured sports: spatial
      determination?

PMID- 15954268
TI  - Genetic variation within and among patches of the clonal species, Phragmites
      australis.

PMID- 15954269
TI  - Aniline and 3-chloroaniline degrading bacteria: genetics and possible
      applications.

PMID- 15954270
TI  - Characterisation of proteins secreted by the plant-parasitic nematode Heterodera
      schachtii.

PMID- 15954271
TI  - Rhizoremediation of a 3,4-dichloroaniline contaminated soil.

PMID- 15954272
TI  - Electrochemical post-treatment of anaerobic digested slurries: removal of
      refractory compounds in a closed nutrient cycle (LSS).

PMID- 15954273
TI  - Do long-term herbicide treatments alter the soil bacterial diversity and
      community structure?

PMID- 15954274
TI  - Biological membrane assisted carbon filtration for reuse of wastewater treatment
      plant effluent.

PMID- 15954275
TI  - Development of a simulation model for the growth and the qualitative evaluation
      of a rose crop.

PMID- 15954276
TI  - Effect of water stress induced by adding polyethylene glycol (PEG 6000) in the
      nutrient solution on the photosynthesis rate of tomato plants (Lycoperiscon
      esculentum cv Nikita).

PMID- 15954277
TI  - Soil respiration in a bio-energy plantation.

PMID- 15954278
TI  - Impact of dewatering and afforestation of contaminated dredged sediment on metal
      fractionation and mobility.

PMID- 15954279
TI  - Field trial setup for heavy metal removal from dredged sediments using intensive
      cultures of the willow Salix viminalis.

PMID- 15954280
TI  - Relationship between heavy metal contents in the spider Pirata piraticus and
      substrate characteristics along the Scheldt estuary.

PMID- 15954281
TI  - Heavy metal contents in reed plants (Phragmites australis) along the river
      Scheldt.

PMID- 15954282
TI  - Seasonal groundwater nitrate dynamics and nitrogen isotope discrimination in a
      riparian zone.

PMID- 15954283
TI  - Identification and quantification of nitrogen removal in a rotating biological
      contactor by 15N tracer techniques.

PMID- 15954284
TI  - Adhesion of bacteria to silicone membranes.

PMID- 15954285
TI  - Adsorption and photocatalytic degradation of trichloroethylene on titanium
      dioxide.

PMID- 15954286
TI  - Removal of mixed chlorinated ethenes and heavy metals in zero valent iron
      systems.

PMID- 15954287
TI  - Bioavailability and ecotoxicity of nickel: effects of water quality
      characteristics.

PMID- 15954288
TI  - Acclimation of the freshwater crustacean Daphnia magna to copper: changes in
      tolerance and energy allocation.

PMID- 15954289
TI  - Retinol and retinyl palmitate as biomarkers of health of environment in Gambusia
      holbrooki in Gharb field, Morocco.

PMID- 15954290
TI  - Sardine oil rich in retinyl esters to fight vitamin a deficiency in Kingdom of
      Morocco.

PMID- 15954291
TI  - River management applications of ecosystem models predicting aquatic
      acroinvertebrate communities based on artificial neural networks (ANNS).

PMID- 15954292
TI  - River restoration simulations by ecosystem models predicting aquatic
      macroinvertebrate communities based on J48 classification trees.

PMID- 15954293
TI  - Application of genetic algorithms for input variables selection of decision tree
      models predicting Mollusca in unnavigable Flemish watercourses.

PMID- 15954294
TI  - Development of a fuzzy expert system for the prediction of macroinvertebrate
      taxa.

PMID- 15954295
TI  - Predicting Gammaridae (Crustaceae, Isopoda) in the Zwalm river basin (Flanders,
      Belgium) by means of fuzzy logic models.

PMID- 15954296
TI  - Short-term behaviour of an experimental constructed wetland at low temperatures.

PMID- 15954297
TI  - Dynamic exposure assessment and modeling.

PMID- 15954298
TI  - Combined nitrate and titrimetric measurements for identification of the
      denitrification process: in calibration of ASMs for BNR systems.

PMID- 15954299
TI  - Modelling greenhouse temperature using ARMAX and ARX systems.

PMID- 15954300
TI  - Effect of spices and herbs towards Shigella sonnei and S. flexneri.

PMID- 15954301
TI  - Modelling of the crystallization kinetics of cocoa butter.

PMID- 15954302
TI  - The effect of phospholipids and water on the isothermal crystallisation behaviour
      of milk fat.

PMID- 15954303
TI  - Two Streptomyces sp. strains able to hydrolyse the Clavibacter exopolymer,
      clavan.

PMID- 15954304
TI  - Screening for grass cell wall polysaccharide converting microorganisms.

PMID- 15954305
TI  - Development of an immunological method to assess bisphenol A migration.

PMID- 15954306
TI  - Nutritional problems of infants in Kilosa district, rural Tanzania, and
      appropriate interventions.

PMID- 15954307
TI  - Evaluation of the influence of bacteria on protein and lipid metabolism in short-
      and long-ripened dry fermented sausages.

PMID- 15954308
TI  - Clover saponins as methane inhibitors and their effect on rumen n utilisation
      efficiency as studied in vitro and in vivo.

PMID- 15954309
TI  - In vitro study of lipolysis and biohydrogenation in cattle: which inoculum to
      use?

PMID- 15954310
TI  - Improving the fatty acid composition of the intramuscular fat of Belgian Blue
      double-muscled bulls.

PMID- 15954311
TI  - Development of an oligidic diet for Orius laevigatus nymphs using a deletion
      addition approach.

PMID- 15954312
TI  - Development of Iphiseius degenerans Berlese (Acari: Phytoseiidae) on four
      different kinds of food sources.

PMID- 15954313
TI  - Ion leakage and wheat seed quality.

PMID- 15954314
TI  - The discarding problem in the North Sea brown shrimp (Crangon Crangon) fishery.

PMID- 15954315
TI  - Consumers and GM food: a divergent relation.

PMID- 15954316
TI  - VOC abatement by means of atmospheric pressure plasmas.

PMID- 15954317
TI  - Construction and characterization of a PPC (phosphoenolpyruvate carboxylase)
      knockout mutant of Escherichia coli.

PMID- 15954318
TI  - [Genetic analysis of atopic diseases].

PMID- 15954319
TI  - [Toll-like receptor (TLR)].

PMID- 15954320
TI  - [Role of mast cells in allergic diseases].

PMID- 15954321
TI  - [Role of eosinophils in allergic inflammation].

PMID- 15954322
TI  - [IgE and allergic diseases].

PMID- 15954323
TI  - [Roles of leukotrienes in immunological and allergic disorders].

PMID- 15954324
TI  - [Pathogenesis of asthma].

PMID- 15954325
TI  - [Role of T cells on the development of airway hyperreactivity].

PMID- 15954326
TI  - [Molecular medicine in asthma].

PMID- 15954327
TI  - [Intractability and remodeling in bronchial asthma].

PMID- 15954328
TI  - [DNA vaccines to allergic diseases and upcoming clinical application].

PMID- 15954329
TI  - [Mechanism of pathogenesis in atopic dermatitis].

PMID- 15954330
TI  - [Skin barrier dysfunction in atopic dermatitis].

PMID- 15954331
TI  - [Mechanism to induce intractable condition of atopic dermatitis].

PMID- 15954332
TI  - [Allergic rhinitis].

PMID- 15954333
TI  - [Allergic sinusitis].

PMID- 15954334
TI  - [Allergic conjunctival disorders].

PMID- 15954335
TI  - [Aspirin-induced asthma (AIA)].

PMID- 15954336
TI  - [Alcohol-induced asthma].

PMID- 15954337
TI  - [Atopic myelitis].

PMID- 15954338
TI  - [Contact dermatitis].

PMID- 15954339
TI  - [Angioneurotic edema, angioedema].

PMID- 15954340
TI  - [Food allergy].

PMID- 15954341
TI  - [Management and treatment of pollinosis in clinic].

PMID- 15954342
TI  - [Drug allergy].

PMID- 15954343
TI  - [Hypersensitivity pneumonitis].

PMID- 15954344
TI  - [Allergic granulomatosis angiitis].

PMID- 15954345
TI  - [Latex allergy, contact urticaria, anaphylaxis, latex-fruit syndrome, powder-free
      gloves].

PMID- 15954346
TI  - [Chemical sensitivity (CS)].

PMID- 15954347
TI  - [Autoantibodies in connective tissue diseases].

PMID- 15954348
TI  - [Identification of disease-susceptible genes of rheumatic diseases].

PMID- 15954349
TI  - [Mechanism for synovial hyperplasia in rheumatoid arthritis].

PMID- 15954350
TI  - [SLE caused by DNase 1 gene mutation].

PMID- 15954351
TI  - [Role of cytokine in the pathogenesis of lupus nephritis].

PMID- 15954352
TI  - [Pathogenesis of granulomatous arteritis].

PMID- 15954353
TI  - [Role of PD-1-mediated signals in regulating autoimmunity].

PMID- 15954354
TI  - [Clearance of apoptotic cells and autoimmunity].

PMID- 15954355
TI  - [Anti-cytokine therapy for connective tissue disease].

PMID- 15954356
TI  - [Cyclosporin for the treatment of systemic autoimmune diseases].

PMID- 15954357
TI  - [Pathogenesis of systemic lupus erythematosus].

PMID- 15954358
TI  - [Pharmacotherapy of SLE].

PMID- 15954359
TI  - [Rheumatoid arthritis].

PMID- 15954360
TI  - [Malignant rheumatoid arthritis].

PMID- 15954361
TI  - [Juvenile rheumatoid arthritis].

PMID- 15954362
TI  - [Felty's syndrome].

PMID- 15954363
TI  - [Palindromic rheumatism].

PMID- 15954364
TI  - [Adult Still's disease: recent progress in basic and clinical research].

PMID- 15954365
TI  - [Scleroderma].

PMID- 15954366
TI  - [Idiopathic inflammatory myopathies].

PMID- 15954367
TI  - [Sjogren's syndrome].

PMID- 15954368
TI  - [Mixed connective tissue disease].

PMID- 15954369
TI  - [Polyarteritis nodosa (PAN)].

PMID- 15954370
TI  - [Recent clinicopathophysiological status and treatment in Wegener's
      granulomatosis].

PMID- 15954371
TI  - [Microscopic polyangiitis].

PMID- 15954372
TI  - [Aortitis syndrome].

PMID- 15954373
TI  - [Temporal arteritis].

PMID- 15954374
TI  - [Henoch-Schonlein purpura].

PMID- 15954375
TI  - [Rheumatic fever (RF)].

PMID- 15954376
TI  - [Polymyalgia rheumatica].

PMID- 15954377
TI  - [Ankylosing spondylitis].

PMID- 15954378
TI  - [Sarcoidosis--immunological features and clinical issues].

PMID- 15954379
TI  - [Behcet's disease].

PMID- 15954380
TI  - [Erythema nodosum].

PMID- 15954381
TI  - [Secondary amyloidosis in patients with rheumatoid arthritis].

PMID- 15954382
TI  - [Kawasaki disease (Kawasaki syndrome)].

PMID- 15954383
TI  - [Goodpasture syndrome].

PMID- 15954384
TI  - [Interstitial pneumonia].

PMID- 15954386
TI  - [Multiple sclerosis and regulatory cells].

PMID- 15954385
TI  - [Myasthenia gravis].

PMID- 15954387
TI  - [Guillain-Barre syndrome].

PMID- 15954388
TI  - [Autoimmune hemolytic anemia].

PMID- 15954389
TI  - [Idiopathic thrombocytopenic purpura].

PMID- 15954390
TI  - [Cold agglutinin disease and paroxysmal cold hemoglobinuria].

PMID- 15954391
TI  - [Paroxysmal nocturnal hemoglobinuria].

PMID- 15954392
TI  - [Autoimmune-associated hemophagocytic syndrome].

PMID- 15954393
TI  - [Autoimmune neutropenia].

PMID- 15954394
TI  - [Chronic graft-versus-host disease].

PMID- 15954395
TI  - [Hyper-IgE syndrome].

PMID- 15954396
TI  - [Antiphospholipid syndrome].

PMID- 15954397
TI  - [Primary biliary cirrhosis (PBC)].

PMID- 15954398
TI  - [Autoimmune hepatitis].

PMID- 15954399
TI  - [Primary sclerosing cholangitis].

PMID- 15954400
TI  - [Ulcerative colitis and Crohn's disease].

PMID- 15954401
TI  - [Autoimmune myocarditis].

PMID- 15954402
TI  - [IgA nephropathy].

PMID- 15954403
TI  - [Nephrotic syndrome].

PMID- 15954404
TI  - [Membranoproliferative glomerulonephritis].

PMID- 15954405
TI  - [Anti-GBM disease].

PMID- 15954406
TI  - [Autoimmune thyroid disease].

PMID- 15954407
TI  - [Autoimmune blistering diseases].

PMID- 15954408
TI  - [Classification of immunodeficiency diseases].

PMID- 15954409
TI  - [Primary immunodeficiency diseases].

PMID- 15954410
TI  - [Severe combined immunodeficiency diseases].

PMID- 15954411
TI  - [Ataxia telangiectasia].

PMID- 15954412
TI  - [Human immunodeficiency virus infection (HIV infection)].

PMID- 15954413
TI  - [Development of vaccine and its immunological mechanism].

PMID- 15954414
TI  - [Vaccine adverse events and causal relationship].

PMID- 15954415
TI  - [Influenza vaccine].

PMID- 15954416
TI  - [Poliomyelitis vaccine].

PMID- 15954417
TI  - [Rubella vaccine].

PMID- 15954418
TI  - [Mumps vaccine].

PMID- 15954419
TI  - [Varicella-zoster virus vaccine].

PMID- 15954420
TI  - [Cholera vaccine].

PMID- 15954421
TI  - [Hepatitis A vaccine].

PMID- 15954422
TI  - [Hepatitis B vaccine].

PMID- 15954423
TI  - [Pneumococcal vaccine].

PMID- 15954424
TI  - [Japanese encephalitis vaccine].

PMID- 15954425
TI  - [Rabies vaccine].

PMID- 15954426
TI  - [HIV vaccine].

PMID- 15954427
TI  - [Cyclosporin].

PMID- 15954428
TI  - [Tacrolimus].

PMID- 15954429
TI  - [Corticosteroids].

PMID- 15954430
TI  - [Mycophenolate mofetil in renal transplantation].

PMID- 15954431
TI  - [Azathioprine].

PMID- 15954432
TI  - [Methotrexate].

PMID- 15954433
TI  - [Mizoribine].

PMID- 15954434
TI  - [Anti IL-2 receptor antibody--basiliximab].

PMID- 15954435
TI  - [Rapamycin].

PMID- 15954436
TI  - [Anti-IL-6 receptor antibody].

PMID- 15954437
TI  - [CD20 antibody for the treatment of systemic autoimmune diseases].

PMID- 15954438
TI  - [Anti-TNF-alpha antibody].

PMID- 15954439
TI  - [Muromonab CD3].

PMID- 15954440
TI  - [CTLA4-Ig].

PMID- 15954441
TI  - Healing architecture.

PMID- 15954442
TI  - REHAB, center for spinal cord and brain injuries Basel, Switzerland.

PMID- 15954443
TI  - Dalseth family dental clinic Apple Valley, Minnesota.

PMID- 15954444
TI  - Yawkey Center for Outpatient Care Boston, Massachusetts.

PMID- 15954446
TI  - Tooth whitening--an update.

PMID- 15954447
TI  - Maxillary alveolar ridge augmentation using distraction osteogenesis: a
      literature review and case report.
AB  - The restoration of the edentulous atrophic anterior maxillary ridge has proved
      difficult. The absence of both gingival and bony alveolar tissue contributes to
      these problems. Numerous techniques to address these issues have been described.
      We report a case of a patient who sustained multiple facial injuries as a
      consequence of an accident, including the loss of the maxillary incisor teeth and
      associated alveolus. This patient underwent fixed implant supported prosthetic
      rehabilitation, following the use of distraction osteogenesis in the
      reconstruction of the edentulous atrophic anterior maxillary ridge.

PMID- 15954448
TI  - A survey of undergraduate orthodontic training and orthodontic practices by
      general dental practitioners.
AB  - PURPOSE OF THE STUDY: To assess satisfaction with undergraduate orthodontic
      training, the variety of treatments undertaken in general practice,
      practitioners' perceived competence in orthodontics and the level of interest in
      continuing education in orthodontics. DESIGN: Cross-sectional questionnaire-based
      study. MATERIALS AND METHODS: A questionnaire was mailed to 520 general
      practitioners in Dublin, Kildare and Wicklow as listed in Irish Dental Council
      Register of Dentists 2003. RESULTS: Forty-six percent of dentists responded. More
      than half (54 per cent) of the respondents were satisfied with both academic and
      clinical aspects of undergraduate training. Twenty-nine percent regularly perform
      orthodontic treatment. Only 60 percent feel comfortable treating orthodontic
      emergencies. Over 70 percent have either already attended or aspire to attend
      further training in orthodontic diagnosis and interceptive orthodontics.
      CONCLUSIONS: Our study indicates that in the greater Dublin area, graduates
      (those qualified less than 10 years) are increasingly satisfied with
      undergraduate teaching. Orthodontic treatment is performed regularly in general
      dental practice with interceptive procedures most often carried out. While
      ability to deal with orthodontic emergencies is not universal, practitioners do
      appear confident to perform a variety of orthodontic procedures. Interest in
      continuing education in orthodontics is very high. Our study indicates that
      participation in continuing education in orthodontics appears to translate into
      greater provision of orthodontic care in general practice.

PMID- 15954449
TI  - The middle mesial canal of mandibular first molars.

PMID- 15954450
TI  - Managing absenteeism--easier than pulling teeth?

PMID- 15954452
TI  - The last step towards a paperless surgery.

PMID- 15954453
TI  - History of the Burn Center of the FNsP Hospital in Ostrava.

PMID- 15954454
TI  - Our first experience with Integra.
AB  - The advantages of Integra have lead to an increase in its use after extensive
      burn injuries, in reconstructive surgery after burns, and abroad in general
      reconstructive surgery as well. At the Burn Center of FNsP Hospital in Ostrava
      Integra was used for the first time in March 2003. Since then, seven patients
      have undergone operations, involving the use of Integra in 14 body areas. In four
      of the patients scars after burns were corrected--on the neck, axilla, two on the
      trunk, two in the popliteal area and one between the toes. In three patients the
      artificial skin was applied after necronectomy. In a 7-month-old baby and in a 2
      year-old child with burn injuries exceeding 25% of the body surface it was
      applied twice on the trunk, once on the upper extremity and once on the lower
      extremity. In an adult female Integra was applied on her neck and axilla after
      burns to a lesser extent. We have evaluated the scars one year after surgery in
      two patients. Cosmetic appearance was good in both of them. We have noted good
      functional result after the reconstruction of axilla. After reconstruction in the
      neck area and reconstruction of the necrectomy in the neck area and axilla, the
      functional results were average. The average functional results in both patients
      are probably due to poor compliance with the immobilization and following
      rehabilitation program.

PMID- 15954455
TI  - Surgical treatment of electrical burns by local flap plastic surgery.
AB  - Electrical burns are a serious problem within burn medicine even though they are
      relatively uncommon. The size of the burn is small, but the wound is often deep,
      and frequently the patient has systemic complications as well. In the majority of
      patients with such injuries immediate surgical intervention is essential,
      consisting of escharotomy, fasciotomy, and debridement of the devitalized
      tissues, necrectomy of the burn area, and closure of the defect by a direct
      suture, a dermo-epidermal graft, or local flap. Our report consists of three case
      studies. The patients underwent local flap plastic surgery after a full thickness
      soft tissue loss. All three patients healed primarily and did not require further
      correction of flaps. Final functional and aesthetic results are very good if the
      local flap is used appropriately.

PMID- 15954456
TI  - Burn injury in children.
AB  - The authors have analyzed the data files of 580 child patients up to 15 years of
      age who were hospitalized at the Burn Center of the FNsP Hospital in Ostrava in
      the years 1999 - 2003. The authors focused on mechanisms of burn injury in
      relation to the age of a child as well as extent, depth, localization, and local
      treatment of the injury. The data file was divided to four age groups: up to two
      years of age, 2 - 5 years of age, 5 - 10 years of age, and 10 - 15 years of age.
      As regards the mechanisms of injury, the authors have analyzed scalding by hot
      liquids, burns due to contact with a hot object, burns due to electric current,
      explosion, and injury caused by burning clothing. Injury by scalding prevails to
      a very significant degree in the youngest children. In the second age group the
      incidence of burn following contact with hot objects increases, as does the
      percentage of children injured by burning of clothing in children aged 5 - 10.
      The older children have increased prevalence of injuries caused by explosions.
      The greatest average extent of an injury is from burning of clothing. Most of the
      areas are burned deeply, localized in more areas of the body, and almost half of
      the cases required surgical intervention. Scalding comes second in terms of
      average extent of an injury. More than half of the injured areas are superficial,
      and areas of injury are different in the individual age groups. We addressed
      about a fifth of the cases surgically. The explosion of combustible materials
      caused a smaller extent of injury, on average, taking third place. The injuries
      were predominantly superficial, most commonly involving the head, trunk, and
      upper extremities. In none of the cases it was necessary for us to operate. Burn
      injuries caused by contact with hot objects are of a smaller extent. More than
      half of the burned areas are deep, localized most commonly in the upper
      extremities. Surgical intervention was necessary in more than half the cases. In
      terms of average extent of an injury, the smallest burn injuries are caused by
      electric current. However, these injuries are deep, and surgical intervention was
      necessary in all cases.

PMID- 15954457
TI  - Critical and severe burn injury in children.
AB  - The authors present a data file of 279 children with severe and critical burn
      injury, hospitalized in the Intensive Care Unit or the Pediatric Resuscitation
      Unit of the FNsP Hospital in Ostrava in the years 1999 - 2003. The severity of
      the burn trauma in children is determined by age, extent, depth, localization,
      circumstances of the injury, its mechanism, and by other serious illnesses of a
      child. The authors have divided the data file into two groups, severe and
      critical, using classification of a burn injury in children according to the
      extent of injury as well as localization and other circumstances (1). Complex
      therapy of extensive burn injuries in children is based on adequate fluid
      resuscitation, treatment of burned areas, algosedation, and appropriate
      antibiotic therapy. The authors have unequivocally confirmed that in the group of
      children with diagnosis of critical burns complications occur more often, while
      the overall course of illness is serious and requires more therapeutical
      interventions than in the group of children with severe burns.

PMID- 15954458
TI  - Social aspects of children hospitalized with a burn trauma.
AB  - Unfavorable socioeconomic conditions lead to an increase of the number of
      injuries in children from a high-risk environment. Based on the literature,
      inappropriate care for children is classified into groups. Various modes of
      behavior of deprived children are supported by practical examples. The negative
      and positive attitudes of nursing personnel towards these children are
      considered.

PMID- 15954459
TI  - Burn injury in senior citizens over 75 years of age.
AB  - This is a retrospective analysis of a group of 67 senior citizens over 75 years
      of age who had been hospitalized at the Burn Center of the FNsP Hospital in
      Ostrava--Poruba in the years 1999 - 2003. We have studied a group of males and
      females, noting their average age, most common causes of burn injuries,
      mechanisms of burn injuries, average extent of burn injuries, and most commonly
      burned body parts. We have also reviewed the seriousness of burn injury in senior
      citizens, factors that complicated the course of treatment as well as its impact
      on the final therapeutic effect. The importance of specific approach and
      individual therapeutic strategy is emphasized. We would also like to emphasize
      the need for complex therapy approach due to secondary diseases that are very
      common in this age group. The treatment of burn patients in this age group is
      very challenging from a personal and economic point of view. The goals of therapy
      are a full recovery and the return of the patient to normal life. However, goals
      and therapeutic results are determined and limited by the above-mentioned
      factors. Nevertheless, every therapeutic success, although partial, should be
      perceived as positive. For the patient, every success from the point of view of
      the ability to take care of himself or herself and the overall quality of life is
      fundamental.

PMID- 15954460
TI  - First experience with the use of vacuum assisted closure in the treatment of skin
      defects at the burn center.
AB  - Morykwas and Argenta developed Vacuum Assisted Closure (VAC) in the early 90s for
      the treatment of tissue defects. In 2004, for the first time at our workplace, we
      used this method in the treatment of six patients between 54 and 91 years of age.
      Two of the patients were treated for a varicose ulcer on a lower extremity, two
      patients for loss of skin after an inflammation secondary to infection, one high
      risk patient for deep burns, and one patient for a deep defect caused by an
      inappropriate medical care. We observed blood circulation improvement in all
      patients, which permitted an early dermo-epidermal graft.

PMID- 15954461
TI  - Comparative study of mandibular glands of Melipona bicolor queens obtained from
      polygynic and monogynic colonies.
AB  - The aim of the present study was analyze, by histological and morphometrical
      studies, mandibular glands of Melipona bicolor queens collected from monogynic
      and polygynic colonies and compare their level of development. The results showed
      that the glands ofphysogastric queens from monogynic colony present a higher
      level of activity in relation to the queens of polygynic colonies; this is
      explained by the fact that just a unique queen controls the monogynic colony. In
      the polygynic colonies, the queens may divide such control to each other.

PMID- 15954462
TI  - Effects of filgrastim on granulopoietic cells of mice pretreated with
      methotrexate.
AB  - We have evaluated the effect of filgrastim on proliferation and differentiation
      activity of granulopoietic cells in mice pretreated with methotrexate. Filgrastim
      was injected daily, from day 8 to 28 after cytotoxic agent administration. The
      granulopoiesis changes were measured by assessment of GM-CFU cells content,
      marrow and spleen granuloid cells pool as well as circulating neutrophils. In MTX
      pretreated mice, bone marrow GM-CFU oscillating values were higher than normal
      values, but these changes were not followed by high proliferative activity in
      granuloid precursor cell compartment. After MTX treatment, filgrastim
      administration was unable to stimulate marrow granulopoiesis as observed in
      normal mice. In the spleen, MTX led to dramatic changes in the proliferative
      activity of GM-CFU cells, but did not result in spleen granuloid cell changes.
      However, filgrastim treatment induced a spleen granuloid amplification, similar
      to the changes observed in circulating neutrophils values. We suggest that these
      findings can be explained by inhibition of differentiation of marrow GM-CFU cells
      into the more mature granulopoietic cells and/or by an inhibited proliferative
      activity of marrow granuloid cells. They can be also explained in terms of an
      unfavorable marrow microenvironment for granulopoiesis, contrary to a supportive
      spleen microenvironment.

PMID- 15954463
TI  - Reduction of beta-glucuronidase and nitroreductase activity by yoghurt in a
      murine colon cancer model.
AB  - Yoghurt feeding inhibits induced colon cancer in mice. Several studies showed the
      immunomodulatory effect of yoghurt which can explain this inhibition. It is
      possible that yoghurt bacteria can also affect gut flora enzymes related to colon
      carcinogenesis as reported for other probiotics in different animal tumours. The
      aim of this work was to evaluate the role of yoghurt starter bacteria and their
      cell-free fermentation products on the reduction of procarcinogen enzyme
      activities (beta-glucuronidase and nitroreductase). Mice injected with 1,2
      dimethylhydrazine (DMH) and fed with yoghurt were used for this study. Mice given
      milk or yoghurt supernatant (cell free extract) were used to evaluate if the
      yoghurt antitumour effect is due to the starter bacteria or other components
      released during fermentation, that could inhibit these enzymes. We determined
      that yoghurt by itself maintained enzymes activities similar or lower than non
      treatment control group, and the enzyme activity was also lower than milk or
      yoghurt supernatant groups. DMH increased the activity of the enzymes. Mice
      injected with DMH and fed cyclically with yoghurt presented lower enzymes
      activities than the tumour control group. Feeding yoghurt decreased
      procarcinogenic enzyme levels in the large intestine contents of mice bearing
      colon tumour. The results of this study provide another mechanism by which
      yoghurt starter bacteria interact with the large intestine of the mice and
      prevent colon cancer.

PMID- 15954464
TI  - Fine structural analysis of the epithelial cells in the hepatopancreas of
      Palaemonetes argentinus (Crustacea, Decapoda, Caridea) in intermoult.
AB  - The aim of this study is to describe the ultrastructure of the hepatopancreas of
      P. argentinus in intermoult. P. argentinus hepatopancreas was studied using
      standard TEM techniques. Each tubule consists of four cellular types: E
      (embryonic), F (fibrillar), R (resorptive) and B (blister like). E-cells have
      embryonic features and some of them were found in mitosis. F, R and B cells
      possess an apical brush border. F-cells have a central or basal nucleus, a
      conspicuous RER, and dilated Golgi cisternae. R cells show a polar organization
      of organelles in three areas: apical, with numerous mitochondria and sER tubules,
      a central area with the nucleus and RER, and a basal area containing a sER-like
      tubule system and mitochondria. B-cells were observed at different stages of
      their life cycle. In an early differentiation stage they comprise an apical
      endocytotic complex and Golgi vesicles. The fusion of endocytotic and Golgi
      vesicles originates subapical vacuoles. During maturation, a big central vacuole
      is formed by coalescence of subapical vacuoles. The central vacuole is eliminated
      by holocrine secretion. The ultrastructure suggests that F-cells synthesize
      proteins, R-cells storage nutrients and B-cells have a secretory or excretory
      function, and confirms the independent origin of F, B and R cells from the
      embryonic cells.

PMID- 15954465
TI  - Comparative study of DNA synthesis and nucleolar organizer regions of sinusoid
      littoral cells in mouse regenerating liver.
AB  - Variations in DNA synthesis (DNAs) and Nucleolar Organizer Regions (NORs) were
      studied in the littoral cell population from regenerating liver of C3HS inbred
      mice standardized for periodicity analysis. Immunohistochemical detection of
      Bromodeoxyuridine (BrdU) with a monoclonal antibody and silver staining of NORs
      (AgNORs) were assessed by means of a digital image analysis system in
      histological sections. Tissue samples were obtained every four hours from the
      30th to the 54th hours after a partial hepatectomy. The results showed, in both
      parameters, a gradual increment of the values during the period studied, with
      highest values (DNAs 107.1 +/- 16.1 SE; AgNORs 77.3 +/- 3.4 SE) located at
      16:00/54 Time of Day / Hours Post-Hepatectomy (TD/HPH), which were significantly
      different (p <0.001) from the values of the first sample (DNAs 38.1 +/- 9.5 SE;
      AgNORs 27.3 +/- 1.0 SE) taken at 16:00/30 TD/HPH. The results of our experiment
      demonstrate the existence of a strong correlation of DNA synthesis measured by
      BrdU immunohistochemistry and AgNORs numbers in sinusoid littoral cells from
      mouse regenerating liver.

PMID- 15954466
TI  - Morphoquantitative evaluation of the duodenal myenteric neuronal population in
      rats fed with hypoproteic ration.
AB  - The purpose of this work was to analyze the morphoquantitative behavior of the
      neurons of the myenteric plexus, as well as the morphometry of the duodenal wall,
      in adult rats fed with normoproteic (22%) and hypoproteic (8%) rations, killed at
      the age of 345 days. For neuronal assessments duodenal whole-mounts stained with
      the Giemsa method were used, and for the evaluation of the duodenal wall routine
      histological processing and staining with Hematoxilin-Eosin were employed. The
      means of the number of neurons in 80 microscopic fields (12.72 mm2) and of the
      size of the neuronal cell bodies did not reveal statistically significant
      differences between the groups, but there was a greater incidence of large
      neurons in the protein restriction group (RP). The duodenum was markedly smaller
      in the RP group and, although there was no difference in the thickness of its
      wall, the mucosa was larger and the muscular layer was smaller in group RP. It
      was concluded that the neuronal and non-neuronal components of the duodenum
      adjust themselves to the nutritional condition, assuring the maintenance of their
      functions.

PMID- 15954467
TI  - Extracellular matrix of ostrich articular cartilage.
AB  - The composition and organization of the extracellular matrix of ostrich articular
      cartilage was investigated, using samples from the proximal and distal surfaces
      of the tarsometatarsus. For morphological analysis, sections were stained with
      toluidine blue and analyzed by polarized light microscopy. For biochemical
      analysis, extracellular matrix components were extracted with 4 M guanidinium
      chloride, fractionated on DEAE-Sephacel and analyzed by SDS-PAGE.
      Glycosaminoglycans were analyzed by electrophoresis in agarose gels. Structural
      analysis showed that the fibrils were arranged in different directions,
      especially on the distal surface. The protein and glycosaminoglycan contents of
      this region were higher than in the other regions. SDS-PAGE showed the presence
      of proteins with molecular masses ranging from 17 to 121 kDa and polydisperse
      components of 67, 80-100, and 250-300 kDa in all regions. The analysis of
      glycosaminoglycans in agarose-propylene diamine gels revealed the presence of
      only chondroitin-sulfate. The electrophoretic band corresponding to putative
      decorin was a small proteoglycan containing chondroitin-sufate and not dermatan
      sulfate, unlike other cartilages. The higher amounts of proteins and
      glycosaminoglycans and the multidirectional arrangement of fibrils seen in the
      distal region may be correlated with the higher compression normally exerted on
      this region.

PMID- 15954468
TI  - [Molecular-genetic approaches to diagnosis and intraspecific typing of causative
      agents of glanders and melioidosis].
AB  - Pathogenic Burkholderia--Burkholderia mallei and Burkholderia pseudomallei--are
      causative agents of glanders and melioidosis, severe infectious diseases of man
      and animals. They are regarded as potential agents of bioterrorism. The existing
      bacteriological and immunological methods of identification of B. mallei and B.
      pseudomallei are not efficient enough for the rapid diagnosis and typing of
      strains. Described in the paper are molecular methods of detection of the agents
      by PCR, hybridization and strain typing made on the basis of bacterial total cell
      protein profiles, RAPD, ribotyping as well as of plasmid and DNA microrestriction
      analyses.

PMID- 15954469
TI  - [Possible mechanisms of implementation of toxic potential of lipopolysaccharides
      of pathogenic bacteria].
AB  - The significance of variability of biological properties of lipopolysaccharides
      (LPS) is discussed in the paper within the pathogenesis of infectious process. On
      the basis of an analysis of published data and of results of independent research
      of two microorganisms (Yersinia pestis and Francisella tularensis) a conclusion
      is made on that a biologically inert LPS form (with a weak cytokine-inducing
      ability, apirogenicity and non-toxicity etc.) is typical of highly pathogenic
      bacteria. It is suggested that the above phenomenon is biologically expedient.
      Presumably, the inert LPS transforms to the active form inside a sensitive host
      and, according to an infection stage, each of them being functionally
      significant. It is the inert status of LPS that enables the pathogens, at the
      initial stages, to surmount freely the humoral and cell barriers of host. As the
      infection progressively aggravates and the proliferation of bacteria modifies
      itself due to LPS micro- and macroorganisms, its chemical structure and
      biopolymer conformation change. Both modification mechanisms enhance the LPS
      toxic potential. In case of a sensitive host, such variations transform the
      biologically inert LPS into a toxically active form with its function of
      endotoxin being realized. There is no LPS modification in a host insensitive to
      such infection, which entails either recovery or prolonged persistence of the
      pathogen inside the microorganism.

PMID- 15954470
TI  - [A study of action of subinhibiting concentrations of antibiotics on the
      expression of genes regulating production of pathogenicity factors in
      Burkholderia cepacia and Pseudomonas aeruginosa].
AB  - Described in the paper are the results of a study of differential expression of
      pathogenicity of B. cepacia and P. aeruginosa in subinhibiting concentrations
      (SIC) of cyprofloxacyne. While identifying genes expressing differentially in the
      antibiotic SIC, genes cepR B. cepacia and P. aeruginosa expressing without
      cyprofloxacyne in the cultivation medium and not expressing in the antibiotic SIC
      were detected. Finally, involvement of cepR B. cepacia in regulating the
      pathogenicity expression factors according to "quorum sensing" is under
      discussion.

PMID- 15954471
TI  - [Different species of Legionella plasmids and virulence].
AB  - Plasmids with a molecular weight of 2.5 to 80 MD were shown to be present in a
      significant portion of different-type Legionella strains including high-virulence
      isolates L. pneumophila, serogroup 1, and L. bozemanii detected both in Russia
      and abroad in different sources. Plasmid-free derivative were obtained from the
      L. pneumophila strains each carrying only one different-size plasmid DNA. The
      variants had the same virulence as the original cultures for chicken embryos and
      guinea pigs, when the latter were infected in the bile sac or through
      intraperitoneal routes, respectively; their virulence was also similar to that of
      strains resistant to the normal serum of guinea pigs. Hence, the infection models
      used by us failed to show any action of plasmids on the virulence of Legionella.

PMID- 15954472
TI  - [Clinical application of VNTR-typing of Mycobacteria tuberculosis strains:
      monitoring of treatment quality and of laboratory service].
AB  - An early diagnosis of super-infection and mixed infection of Mycobacteria
      tuberculosis is highly important for the correction of an assigned treatment and
      for a positive prognostication. An analysis of loci with varying tandem repeats
      (VNTR) is a simple in use and reproducible method of M. tuberculosis genotyping.
      Thirty-seven serial isolates of M. tuberculosis from 12 patients with pulmonary
      tuberculosis including changing resistance to TB drugs registered in follow-up
      and treatment underwent VNTR-typing for 6 loci: ETR-A, C, E, V1, V3 and V4. Both
      super-infection and mixed infection were shown in 33.3% of cases to cause changes
      in the profile of resistance to TB drugs. In 3 patients, changes in the drug
      resistance profile were accompanied by a substitution of a colonizing strain for
      an epidemic clonal variant of the Beijing family with the 445446 genotype.
      Whereas in one patient, there was a substitution of the Beijing strain for the
      genotype 222422 strain, which is typical of M. tuberculosis with the S42
      spoligotype. One intermediate serial isolate from the above patient had a mixed
      culture of 2 polyresistant strains of M. tuberculosis (445476 + 222422). In one
      case, the substitution of the infecting strain for a strain with changed
      genotypes and profiles of resistance to antibiotics occurred twice within an
      interval of 5-6 months. The 343543 genotype strain changed for the 452562
      genotype strain and then--for the 445466 genotype strain; the final genotype
      variant belonged to the Beijing family. Serial isolates from 8 patients retained
      their original genotype (Beijing). In such cases, the changing spectrum of
      resistance to TB drugs can be associated with the secondary drug resistance
      acquired by strains in the process of treatment or with errors of laboratory
      equipment. Finally, the VNTR analysis is a rapid, easy-in-use and effective tool
      for the systemic typing of M. tuberculosis isolates in clinical practice.

PMID- 15954473
TI  - [Comparative analysis of total cell protein electrophoregram of pathogenic
      Burkholderia].
AB  - Whole-cell proteins of 22 strain of Burkhoderia pseudomallei, including 13 B.
      mallei, 5 B. cepacia strains and 14 strains of opportunistically pathogenic
      Pseudomonas defined by 1D SDC-PAAG electrophoresis. Electrophoregrams contained
      35 to 45 protein fractions sized 19 to 130 kDa, which were highly reproductive.
      On the basis of computer-aided comparative analysis of protein patterns the
      interspecies and intraspecies grouping of studied microorganisms was made. The
      cluster analysis of the similarity matrix of protein spectra made it possible to
      allocate two groups of strains at the level of similarity of 78%. Group I was
      formed by Burkholderia species that previously belonged to the II RNA-DNA
      homology group of Pseudomonas: B. pseudomallei, B. mallei, B. cepacia. All
      Pseudomonas species were added to the 2nd Group: P. aeruginosa, P. stutzeri, P.
      testosterone, P. fluorescens, P. putida, P. mendocina. Four phenons were isolated
      among the strains of B. pseudomallei and 2 phenons--among the strains of B.
      mallei at the threshold similarity level (89%). The authors conclude that the
      comparative analysis of electrophoregrams of whole-cell proteins can be useful in
      the identification and typing of pathogenic Burkholderia.

PMID- 15954474
TI  - [Designing of the pp65 recombinant antigen of human cytomegalovirus and
      investigation of its immunochemical properties].
AB  - The primary and secondary structures of the pp65 phosphoprotein of human
      cytomegalovirus coded by the UL83 gene were studied by the methods of computer
      aided analysis. An immunodominant protein fragment with 3 antigenic determinant
      was detected. The UL83 fragment coding the selected region was amplified and
      cloned in bacterial expressing vector. The recombinant protein was obtained and
      purified. On the basis of ELISA findings it was acknowledged as possible to use
      the pp65 recombinant protein jointly with pp150 and p52 in the diagnosis of
      antibodies specific to human cytomegalovirus.

PMID- 15954475
TI  - [Antiviral action of membranotropic compounds modified by adamantane and
      norbornene pharmacophores exerted on different HIV-1 strains].
AB  - The anti-HIV activity of new membranotropic compounds, i.e. of the
      polycarboxylate matrix and of its derivatives modified by adamantane and
      norbonene, was studied in respect of HIV-1 strains, whose tropicity to
      coreceptors CCR5 and CXCR4 was different, as well as in respect of HIV-1 variants
      resistant to azidothymidine (AZT) in a continuous culture of human lymphoid cells
      (MT-4) and in mononuclear cells of peripheral blood from healthy donors. Testing
      of complex compounds in a culture of infected MT-4 human lymphoid cells showed an
      effective inhibition of viral reproduction of LAV.04 (CXCR4-tropic variant) and
      of HIV11(EVK) as well as AZT-resistant variants. The studied pharmacophores
      modified compounds displayed, in infection of the primary culture of human
      mononuclear cells of the HIV-1 R5 and X4 strains, a notable antiviral activity
      with their HIV efficiency significantly exceeding the one of the original matrix.

PMID- 15954476
TI  - [Cytokine TNFalpha-induced stimulation of bacterial growth in vitro].

PMID- 15954477
TI  - A survey of vaccine coverage among Iranian final-year medical students.

PMID- 15954478
TI  - Polymicrobial deep joint replacement infection temporally associated with
      building construction: a case series.

PMID- 15954479
TI  - Toward better benchmarking.

PMID- 15954480
TI  - Hospital-related determinants for surgical-site infection following hip
      arthroplasty.
AB  - OBJECTIVE: To determine hospital-related risk factors for surgical-site infection
      (SSI) following hip arthroplasty. DESIGN: Prospective, multicenter cohort study
      based on surveillance data and data collected through a structured telephone
      interview. With the use of multilevel logistic regression, the independent effect
      of hospital-related characteristics on SSI was assessed. SETTING: Thirty-six
      acute care hospitals in the Dutch surveillance network for nosocomial infections
      (PREZIES), from 1996 to 2000. PATIENTS: Thirteen thousand six hundred eighty
      patients who underwent total or partial hip arthroplasty. RESULTS: A high annual
      volume of operations was associated with a reduced risk of SSI (risk-adjusted
      risk ratio [RR] per 50 extra operations, 0.85; 95% confidence interval [CI95],
      0.74-0.97). With each extra full-time-equivalent infection control staff member
      per 250 beds available for prevention of SSI, the risk for SSI was decreased (RR,
      0.48; CI95, 0.16-1.44), although the decrease was not statistically significant.
      Hospital size, teaching status, university affiliation, and number of surgeons
      and their years of experience showed no important association with the risk of
      SSI. CONCLUSION: Undergoing surgery in a hospital with a low volume of operations
      increases a patient's risk of SSI.

PMID- 15954481
TI  - Rates of surgical-site infection: an international comparison.
AB  - OBJECTIVES: To quantify the occurrence of surgical-site infections (SSIs) in an
      Italian region and to estimate the proportion of potentially avoidable infections
      through benchmarking comparison. DESIGN: Prospective study during 1 month based
      on a convenience sample of surgical patients admitted to 31 public hospitals. All
      of the patients undergoing an intervention included among the 44 operative
      procedures of the National Nosocomial Infections Surveillance (NNIS) System were
      enrolled. Ninety-five percent of the patients were actively observed after
      discharge for up to 30 days for all of the operations and for up to 1 year for
      operations involving implantation. RESULTS: Among the 6,167 operative procedures
      studied, 290 infections were recorded (4.7 per 100 procedures), 206 (71%) of
      which were SSIs (3.3 per 100 procedures; 95% confidence interval, 2.9-3.9). One
      hundred thirty-five SSIs (65.5%) were superficial infections, 53 (25.7%) were
      deep infections, and 12 (5.8%) were organ-space infections; in 6 cases (2.9%),
      the type of SSI was not recorded. The frequency of SSIs observed in this study
      was significantly higher for several procedures than that expected when the NNIS
      System rates (standardized infection ratio [SIR] ranging from 1.77 to 6.42) or
      the Hungarian rates (SIR ranging from 1.28 to 3.04) were applied to the study
      population. CONCLUSIONS: The high intensity of postdischarge surveillance can in
      part explain the differences observed. To allow for meaningful benchmarking
      comparison, in addition to intrinsic patient risk, data on the intensity of
      postdischarge surveillance should be included in published reports.

PMID- 15954482
TI  - Surgical-site infections following cesarean section in an Estonian university
      hospital: postdischarge surveillance and analysis of risk factors.
AB  - OBJECTIVES: To evaluate a multi-method approach to postdischarge surveillance of
      surgical-site infections (SSIs) and to identify infection rates and risk factors
      associated with SSI following cesarean section. DESIGN: Cross-sectional survey.
      SETTING: Academic tertiary-care obstetric and gynecology center with 54 beds.
      PATIENTS: All women who delivered by cesarean section in Tartu University Women's
      Clinic during 2002. METHODS: Infections were identified during hospital stay or
      by postdischarge survey using a combination of telephone calls, healthcare worker
      questionnaire, and outpatient medical records review. SSI was diagnosed according
      to the criteria of the Centers for Disease Control and Prevention National
      Nosocomial Infections Surveillance System. RESULTS: The multi-method approach
      gave a follow-up rate of 94.8%. Of 305 patients, 19 (6.2%; 95% confidence
      interval [CI95], 3.8-9.6) had SSIs. Forty-two percent of these SSIs were detected
      during postdischarge surveillance. We found three variables associated with
      increased risk for developing SSI: internal fetal monitoring (odds ratio [OR],
      16.6; CI95, 2.2-125.8; P = .007), chorioamnionitis (OR, 8.8; CI95, 1.1-69.6; P =
      .04), and surgical wound classes III and IV (OR, 3.8; CI95, 1.2-11.8; P = .02).
      CONCLUSIONS: The high response rate validated the effectiveness of this kind of
      surveillance method and was most suitable in current circumstances. A challenge
      exists to decrease the frequency of internal fetal monitoring and to treat
      chorioamnionitis as soon as possible.

PMID- 15954483
TI  - Molecular characterization of Streptococcus pyogenes isolates to investigate an
      outbreak of puerperal sepsis.
AB  - OBJECTIVE: To describe microbiological characteristics and epidemiologic features
      of an outbreak of postpartum endometritis. METHODS: Various markers were
      investigated in five patients and three throat carriage isolates of Streptococcus
      pyogenes obtained during an outbreak of endometritis occurring in a 13-week
      period. Molecular characterization included biotyping, T-serotyping, emm gene
      sequence and restriction, pulsed-field gel electrophoresis (PFGE), and random
      amplified polymorphic DNA (RAPD) analysis. RESULTS: Biotype, T-serotype, and
      genotypic data (emm analysis, PFGE, and RAPD analysis) revealed a close
      relationship among the isolates from three patients, suggesting that cross
      contamination had occurred. These isolates were biotype 1, T type 28, and emm
      type 28. The isolates from one patient and one carrier differed from those of the
      index patient by minor variations of the emm amplicon restriction pattern, PFGE
      pattern, or RAPD pattern. The remaining isolates were phenotypically and
      genetically different. CONCLUSION: Identification of different isolates
      demonstrated that different strains may circulate simultaneously during a true
      outbreak and that the predominant strain might persist for several months.

PMID- 15954484
TI  - The wound care team: a new source of group a streptococcal nosocomial
      transmission.
AB  - BACKGROUND: In August 2001, the Centers for Disease Control and Prevention (CDC)
      notified the Texas Department of Health (TDH) of an unusually high number of
      wounds infected with group A streptococci (GAS) in an acute care facility. The
      TDH initiated an investigation, ultimately identifying 28 cases of non
      pharyngeal, non-community-acquired GAS that had occurred between December 2000
      and August 2001 and resulted in 3 deaths and 4 nonfatal cases of invasive
      disease. Ten specimens were sent to the CDC for emm typing; all isolates were emm
      type 114. However, the source of the outbreak could not be confirmed through
      laboratory testing at that time. METHODS: A case-control study was conducted
      comparing the 10 case-patients with 52 control-patients with wounds that were not
      infected with GAS. Age, gender, type of wound, underlying medical conditions, and
      treatment by the wound care team were examined for association with GAS
      infection. RESULTS: The odds of having wound care team treatment versus not
      having it were 424.2 (95% confidence interval, 19.0 to 9,495.2) among case
      patients when compared with control-patients. No other risk factor showed this
      magnitude of association. CONCLUSIONS: This study provided overwhelming
      epidemiologic evidence that the wound care team was the means of transmission.
      One year later, when two patients receiving wound care were concurrently
      diagnosed as having GAS, a member of the wound care team was found to be GAS
      positive for the matching emm type. This is the first report of a GAS hospital
      outbreak linked to a wound care team.

PMID- 15954485
TI  - Surgical-site infection after cardiac surgery: incidence, microbiology, and risk
      factors.
AB  - OBJECTIVE: To identify risk factors associated with surgical-site infection
      according to the depth of infection, the cardiac procedure, and the National
      Nosocomial Infections Surveillance System risk index. DESIGN: Prospective survey
      conducted during a 12-month period. SETTING: A 48-bed cardiac surgical department
      in a teaching hospital. PATIENTS: Patients admitted for cardiac surgery between
      February 2002 and January 2003. RESULTS: Surgical-site infections were diagnosed
      in 3% of the patients (38 of 1,268). Of the 38 surgical-site infections, 20 were
      superficial incisional infections and 18 were mediastinitis for incidence rates
      of 1.6% and 1.4%, respectively. Cultures were positive in 28 cases and the most
      commonly isolated pathogen was Staphylococcus. A National Nosocomial Infections
      Surveillance System risk index score of 2 or greater was associated with a risk
      of surgical-site infection (relative risk, 2.4; P < .004). Heart transplantation,
      mechanical circulatory assistance, coronary artery bypass graft with the use of
      internal mammary artery, and reoperation for cardiac tamponade or pericard
      effusion were independent risk factors associated with surgical-site infection.
      CONCLUSIONS: Data surveillance using incidence rates stratified by cardiac
      procedure and type of infection is relevant to improving infection control
      efforts. Risk factors in patients who developed superficial infection were
      different from those in patients who developed mediastinitis. Coronary artery
      bypass graft using internal mammary artery was associated with a high risk of
      surgical-site infection, and independent factors such as reoperation for cardiac
      tamponade or pericard effusion increased the risk of infection.

PMID- 15954486
TI  - Incidence of and risk factors for surgical-site infections in a Peruvian
      hospital.
AB  - OBJECTIVE: To determine the incidence of and risk factors for surgical-site
      infections (SSIs) after abdominal surgery. DESIGN: A cohort study was conducted
      from January to June 1998. CDC criteria for SSI and the NNIS System risk index
      were used. SETTING: A tertiary-care hospital in Peru. PATIENTS: Adult patients
      undergoing abdominal surgery who consented were enrolled and observed until 30
      days after surgery. Patients who had undergone surgery at another hospital or who
      died or were transferred to another hospital within 24 hours after surgery were
      excluded. RESULTS: Four hundred sixty-eight patients were enrolled. Their mean
      age was 37.2 years. One hundred twenty-five patients developed SSIs, 18% of which
      were identified after discharge. The overall incidence rate (IR) was 26.7%. The
      IR was 13.9% for clean, 15.9% for clean-contaminated, 13.5% for contaminated, and
      47.2% for dirty interventions. The IR was 3.6% for NNIS System risk index 0 and
      60% for index 3. Risk factors for SSI on logistic regression analysis were dirty
      or infected wound (RR, 3.8; CI95, 1.7-8.4), drain use longer than 9 days (RR,
      6.0; CI95, 2.5-12.5), and length of surgery greater than the 75th percentile (RR,
      2.1; CI95, 1.0-4.4). Patients with SSI had a longer hospital stay than did non
      infected patients (14.0 vs 6.1 days; p < .001). CONCLUSIONS: SSI is a major
      problem in this hospital, which has a higher IR (especially for clean
      interventions) than those of developed countries. In developing countries,
      prevention of SSI should include active surveillance and interventions targeting
      modifiable risk factors.

PMID- 15954487
TI  - Evaluation of hospital and patient factors that influence the effective
      administration of surgical antimicrobial prophylaxis.
AB  - OBJECTIVE: To analyze and model the patient and healthcare system factors that
      may interfere with the appropriate administration of surgical antimicrobial
      prophylaxis. DESIGN: Between 1994 and 1998, surgical-site surveillance data were
      collected prospectively for a cohort of eligible surgical patients. For all
      cases, and each individual procedure (cardiothoracic, colonic, gynecologic,
      orthopedic, or vascular), forward stepwise multiple logistic regression was
      applied to relate key hospital and patient factors to an effective first
      prophylactic dose (ie, appropriate administration time, dose, route, and drug).
      SETTING: A 450-bed, tertiary-care teaching hospital in Canada. PATIENTS: A total
      of 4,835 patients admitted for surgical procedures who required antimicrobial
      prophylaxis. RESULTS: Factors positive for an effective first prophylactic dose
      for all cases were when an order was written (OR, 19.7; CI95, 9.1-42.7; P < .001)
      and given in the operating room (OR, 13.9; CI95, 7.5-25.6; P < .001). Factors
      negative for an effective first prophylactic dose were beta-lactam allergy (OR,
      0.49; CI95, 0.4-0.61; P < .001) and same-day surgery (OR, 0.57; CI95, 0.4-0.82; P
      < .001). CONCLUSIONS: With few exceptions, the four factors included in the
      procedure models showed that when a preoperative order was written or the
      antibiotic was given in the operating room, a patient was more likely to receive
      an effective first prophylactic dose. Conversely, when a patient had a beta
      lactam allergy or the surgery was performed on the day the patient was admitted,
      the administration of an effective first prophylactic dose was less likely.

PMID- 15954488
TI  - A comparative study of ethylene oxide gas, hydrogen peroxide gas plasma, and low
      temperature steam formaldehyde sterilization.
AB  - OBJECTIVE: To compare the efficacies of ethylene oxide gas (EOG), hydrogen
      peroxide gas plasma (PLASMA), and low-temperature steam formaldehyde (LTSF)
      sterilization methods. METHODS: The efficacies of EOG, PLASMA, and LTSF
      sterilization were tested using metal and plastic plates, common medical
      instruments, and three process challenge devices with narrow lumens. All items
      were contaminated with Bacillus stearothermophilus spores or used a standard
      biological indicator. RESULTS: EOG and LTSF demonstrated effective killing of B.
      stearothermophilus spores, with or without serum, on plates, on instruments, and
      in process challenge devices. PLASMA failed to adequately sterilize materials on
      multiple trials in several experiments, including two of three plates, two of
      three instruments, and all process challenge devices. CONCLUSIONS: Our results
      suggest that PLASMA sterilization may be unsuccessful under certain conditions,
      particularly when used for items with complex shapes and narrow lumens.
      Alternatively, LTSF sterilization demonstrates excellent efficacy and is
      comparable to EOG sterilization. LTSF could potentially act as a substitute if
      EOG becomes unavailable due to environmental concerns.

PMID- 15954489
TI  - Peracetic acid in the disinfection of a hospital water system contaminated with
      Legionella species.
AB  - OBJECTIVE: To assess the efficacy of an alternative disinfection method for
      hospital water distribution systems contaminated with Legionella. METHODS:
      Disinfection with peracetic acid was performed in a small hospital contaminated
      with L. pneumophila serotype 1. The disinfectant was used at concentrations of 50
      ppm (first three surveillance phases) and 1,000 ppm (fourth surveillance phase)
      for 30 minutes. RESULTS: Environmental monitoring revealed that disinfection was
      maintained 1 week after treatment; however, levels of recontamination surpassing
      baseline values were detected after approximately 1 month. Comparison of water
      temperatures measured at the distal outlets showed a statistically significant
      association between temperature and bacterial load. The circulating water
      temperature was found to be lower in the two wards farthest away from the hot
      water production plant than in other wards. It was thought that the lower water
      temperature in the two wards promoted the bacterial growth even after
      disinfection. CONCLUSION: Peracetic acid may be useful in emergency situations,
      but does not provide definitive protection even if used monthly.

PMID- 15954490
TI  - Duration of virus shedding after trivalent intranasal live attenuated influenza
      vaccination in adults.
AB  - OBJECTIVE: To characterize the probability and duration of viral shedding among
      adults given trivalent live attenuated influenza vaccine (LAIV). DESIGN:
      Prospective surveillance study. METHODS: Nasal wash samples were collected from
      adult volunteers at baseline and on days 3, 7, and 10 and between days 17 and 21
      following intranasal LAIV vaccination. The presence, titer, and identification of
      each specific strain of influenza virus shed were determined by standard
      methodology. RESULTS: Twenty subjects received LAIV. No samples were positive for
      influenza virus at baseline. After LAIV vaccination, influenza virus was
      recovered from 10 of 20 vaccinees on day 3, from 1 of 18 vaccinees on day 7, and
      from none of the samples on days 10 or 17 through 21. Vaccinees who shed vaccine
      virus were significantly younger than those who did not (mean age, 26.4 vs 38.6
      years; P < .01). Although the presence of specific mucosal immunoglobulin A to
      influenza B was associated with significantly less shedding of influenza B after
      vaccination (P = .02), associations of shedding with other measures of immunity
      were not detected. CONCLUSION: The duration of shedding of vaccine virus after
      LAIV in adults i s limited and may be associatedwith an individual's prior
      influenza vaccination history.

PMID- 15954491
TI  - Conserved 5S and variable 45S rDNA chromosomal localisation revealed by FISH in
      Astyanax scabripinnis (Pisces, Characidae).
AB  - Fluorescence in situ hybridisation (FISH) and double FISH experiments were
      carried out to ascertain the chromosomal distribution pattern of the 45S and 5S
      ribosomal (r) DNAs in four populations of the characid fish Astyanax scabripinnis
      -a group considered to be a species complex for its wide karyotypical and
      morphological diversity. The results regarding the 45S rDNA agreed with this
      hypothesis, since these sites showed intra- and inter-populational, numerical and
      positional variations. However, the data obtained with the 5S rDNA probe revealed
      a highly conserved chromosomal distribution pattern of these sequences among
      individuals of each population, as well as among the populations analysed. We
      consider this contrasting situation as a functional divergence between 45S and 5S
      ribosomal DNAs, which may reflect the localisation of these sequences in distinct
      nuclear compartments, leading them to undergo differentiated evolutionary
      processes.

PMID- 15954492
TI  - Polytene chromosomes of an archipelagic subgenus, Inseliellum (Diptera:
      Simuliidae).
AB  - The black fly subgenus Inseliellum is present on a series of archipelagos in the
      South Pacific. In this study, larval polytene chromosome maps of six Inseliellum
      species are presented. Chromosomal relationships among taxa were determined
      through shared fixed inversions or chromosomal landmark positioning. Three fixed
      inversions (IL-2, IIS-1, and IIIS-1) were shared among species, as was the
      position of the nucleolar organizer (NO) (IL or IIL). Comparisons to two
      previously studied species of Inseliellum are included to produce a cytological
      transformation series among eight taxa. The NO position defines two clades in the
      phylogeny of Inseliellum, herein named the NO-IL and NO-IIL clades. The utility
      of this cytological data set is discussed.

PMID- 15954493
TI  - Chromosomal diversification of reef fishes from genus Centropyge (Perciformes,
      Pomacanthidae).
AB  - The genus Centropyge is remarkable for species richness, composing a highly
      specialized fish group amongst members from family Pomacanthidae. However,
      cytogenetical reports are nearly absent in these animals. New data are provided
      from karyotypical studies carried out on Centropyge aurantonotus from the
      Brazilian coast of the Atlantic Ocean and C. ferrugatus from the Philippines Sea
      of the Indo-Pacific Ocean. Both species present 2n = 48 but karyotypes are
      differentiated by fundamental number. C. aurantonotus has a great number of
      biarmed chromosomes (4 m + 14 sm + 16 st + 4 a), while C. ferrugatus presents
      only acrocentric chromosomes. Single nucleolar organizer regions (NORs) are
      located at interstitial position of an acrocentric pair in C. ferrugatus and on
      short arms of a subtelocentric pair in C. aurantonotus, as confirmed by
      fluorescent in situ hybridization (FISH) with 18S rDNA probes. Heterochromatin is
      distributed over NOR and centromeric regions in both species, but additional GC
      rich heterochromatic blocks on short arms of up to eight chromosomal pairs can be
      detected in C. aurantonotus. 5S rDNA segments were located interstitially on two
      chromosomal pairs in C. ferrugatus and on nine pairs in C. aurantonotus, mostly
      equivalent to heterochromatic blocks on short arms of biarmed chromosomes. C.
      ferrugatus can be considered a species in which basal chromosomal features
      proposed for modern Teleosteans were conserved. The derived karyotype pattern of
      C. aurantonotus seems to be determined by pericentric inversions and
      heterochromatin addition which probably determined the notorious dispersion of 5S
      rRNA (pseudo)genes. It is demonstrated that, even within a group generally
      characterized by cytogenetical homogeneity as the family Pomacanthidae,
      diversified karyotypes can be found.

PMID- 15954494
TI  - GENEHUNTER versus SimWalk2 in the context of an extended kindred and a
      qualitative trait locus.
AB  - GENEHUNTER and SimWalk2 are among the most commonly used software for parametric
      multipoint linkage analysis. In the context of extended kindred analysis,
      GENEHUNTER has a limitation in terms of the number of individuals it can handle.
      One solution is to manually split the kindred into smaller pedigrees. SimWalk2
      can handle a much larger number of individuals. However, its major drawback is
      the time it takes to process the data when compared to GENEHUNTER. Aside from the
      limitations of each program, when studying extended kindreds researchers are
      typically confronted with missing data. In this work we used simulated genotype
      data based on the structure of a real extended pedigree in order to compare the
      results obtained through GENEHUNTER and SimWalk2, evaluate the effect of
      discarding individuals and splitting the kindred on the logarithm of odds (lod)
      score, and to assess how missing data affect the performance of each program. Our
      results show that (1) for pedigrees of a moderate size, GENEHUNTER and SimWalk2
      produce nearly the same results; (2) when using GENEHUNTER, either splitting the
      kindred into smaller sub-pedigrees or discarding individuals has an adverse
      effect when compared to the results obtained when using SimWalk2 with the whole
      pedigree; and (3) the performance of both programs is qualitatively similar in
      the missing data scenario. These conclusions are based on the sample
      distributions of the lod score values and of the estimates of the recombination
      fraction.

PMID- 15954495
TI  - Molecular and chromosomal analysis of ribosomal cistrons in two cartilaginous
      fish, Taeniura lymma and Raja montagui (Chondrichthyes, Batoidea).
AB  - We used silver nitrate staining, CMA3 and FISH to study the chromosomal
      localization of both the major ribosomal genes and the nucleolar organizer
      regions as well as that of the minor ribosomal genes (5S rDNA) in two species of
      Batoidea, Taeniura lymma (Dasyatidae) and Raja montagui (Rajidae). In both
      species, all the metaphases examined showed the presence of multiple NOR-bearing
      sites, while the gene for 5S rRNA proved to be localized on two chromosome pairs.
      Furthermore, one of the two 5S rDNA sites in T. lymma was shown to be co
      localized with the major ribosomal cluster. The presence of multiple nucleolar
      organizer regions in the two species might be interpreted as being the result of
      intraspecific polymorphisms, or as a phenomenon of the amplified transposition of
      mobile elements of the genome. We also determined the nucleotide sequence of the
      5S rRNA gene, consisting of 564 bp in R. montagui and 612 bp in T. lymma. We also
      found TATA-like and (TGC)n trinucleotides, (CA)n dinucleotides and (GTGA)n
      tetranucleotides, which probably influence gene regulation.

PMID- 15954496
TI  - Quantitative assessment of heteroplasmy levels in Senecio vulgaris chloroplast
      DNA.
AB  - Heteroplasmy in coding chloroplast DNA was only recently shown to occur and was
      so far not quantitatively assessed. We present a quantitative analysis of cpDNA
      heteroplasmy levels at a triazine-resistance determining site within and between
      individual Senecio vulgaris plants. Detectable levels of heteroplasmic haplotypes
      were observed in all tested plants. As expected, the levels of heteroplasmy vary
      greatly between plants. However, even within individual plants, the fraction of
      one haplotype may cover a range from below 1% to well over 90%. Our results
      suggest that heteroplasmy may be a common phenomenon in S. vulgaris. Possible
      consequences for molecular diagnostics of chloroplast encoded traits as well as
      evolutionary consequences of chloroplast heteroplasmy are discussed.

PMID- 15954497
TI  - Microclinal variation for ovariole number and body size in Drosophila
      melanogaster in 'Evolution Canyon'.
AB  - Sites that display strong environmental contrasts in close proximity, such as
      'Evolution Canyon' on Mt. Carmel, Israel, are natural theatres for investigating
      adaptive evolution in action. We reared Drosophila melanogaster from collection
      sites along altitudinal transects on the north- and south-facing canyon slopes in
      each of three temperature environments, and assessed genetic variation in
      ovariole number and body size between and within collection sites, and
      temperature plasticity. Both traits exhibited significant genetic variation
      within collection sites and phenotypic plasticity in response to temperature, but
      not genetic variation for plasticity. Between-site genetic variation in ovariole
      number was negatively correlated with altitude on both slopes of the canyon, and
      collections from the north- and south-facing slopes were genetically
      differentiated for male, but not female, body size. Genetic variation between
      sites within easy dispersal range is consistent with the action of strong natural
      selection, although neither the selective agent(s) nor the direct targets of
      selection are known.

PMID- 15954498
TI  - Allozyme relationships in hypostomines (Teleostei: Loricariidae) from the Itaipu
      Reservoir, Upper Rio Parana basin, Brazil.
AB  - In an allozyme electrophoresis survey of 15 hypostomine species from the Itaipu
      Hydroelectric Reservoir, 25 loci from 14 enzyme systems were scored. Allozyme
      data allowed recording diagnostic genetic markers for all species analyzed and
      for some species groups within Hypostomus, a taxon which is taxonomically still
      unresolved in the Upper Rio Parana basin. The mean expected heterozygosity of the
      species was considerably variable and hypotheses to tentatively explain this
      variation are discussed. A cladogram based upon the allelic frequencies of the
      species analyzed was produced by the continuous maximum likelihood method:
      Rhinelepis aspera and M. parananus were separated from the species of
      Hypostominae by a long branch length. Pterygoplichthys anisitsi was the sister of
      all the representatives of the genus Hypostomus. Within Hypostomus, two main
      clades were produced: in the first, H. cochliodon was the sister of the species
      comprising the H. plecostomus group, and in the second, the tree showed the
      following relationships: (H. albopunctatus (H. regani + Hypostomus sp. 3) + (H.
      margaritifer (H. microstomus (Hypostomus sp. 1 (H. ternetzi + Hypostomus sp. 2)).
      Hypostomus ternetzi and Hypostomus sp. 2 are referred to here as representatives
      of the H. ternetzi group.

PMID- 15954499
TI  - Evidence for introgression in differentiated North-American and Finnish
      Drosophila montana populations.
AB  - The virilis group species Drosophila montana is widely distributed around the
      northern hemisphere. Here we show that it consists of at least two well
      differentiated populations (Finnish and North-American populations) that have
      been diverging for the last 0.55-0.95 My. These populations show significant
      chromosomal, behavioural and morphological differences, but no apparent
      postzygotic isolation. Evidence for introgression is found for both Finnish and
      North-American populations at two out of the three X-linked genes (fused, elav
      and su(s)) studied here. In the light of these findings, previously reported
      evidence for selective sweeps in D. montana populations is re-evaluated.

PMID- 15954500
TI  - CAG repeat length in an infertile male population of Irish origin.
AB  - The androgen receptor (AR) gene, located on the X chromosome, is an important
      regulator of human spermatogenesis. In the past decade, the link between the CAG
      polyglutamine tract, situated on exon one of the AR gene, and reduced
      spermatogenesis has become a controversial one. Alterations in the length of the
      CAG polyglutamine tract have been associated with prostate cancer at a reduced
      intrinsic length and neuromuscular diseases at a CAG repeat length of > or = 40.
      Minimal intermediate increases have been linked with depressed spermatogenesis in
      infertile males. Asian and Australian groups have published an association
      between increased CAG repeat length and reduced spermatogenesis while many
      European studies have found no such association. The aim of this study was to
      document the association between increased CAG repeat length and reduced
      spermatogenesis in a group of Irish infertile males and controls known to have
      fathered at least one child. The study employed the ABI 377 DNA sequencer to size
      the CAG repeat region of exon one of the AR gene in each group. Statistical
      analysis revealed no actual link between the length of the CAG tract and a
      reduction of spermatogenesis in a cohort of infertile patients (n = 66) of Irish
      ethnic origin when compared to a fertile control group (n = 77) (p = 0.599).

PMID- 15954501
TI  - Secale cereale inter-microsatellites (SCIMs): chromosomal location and genetic
      inheritance.
AB  - The polymerase chain reaction (PCR) was used to locate Sectale cereale (inter
      simple sequence repeat ISSR) or Secale cereale inter-microsatellite (SCIM)
      markers using wheat-rye addition lines in order to develop a set of molecular
      markers distributed on the seven rye chromosomes. The number of SCIM markers
      located on 1R, 2R, 3R, 4R, 5R, 6R and 7R chromosomes were 4, 3, 12, 3, 2, 9 and
      8, respectively. Therefore, a total of 41 new SCIMs were located on the seven rye
      chromosomes. The segregation of the 63 different SCIM markers in three different
      F2 was studied. The observed ISSR segregations were the 3:1 (50.7%), the 15:1
      (12.7%) and the 1:1 (14.2%). The linkage analysis carried out indicated that
      seven of the segregating SCIMs were linked to chromosome 7R and two were linked
      to chromosome 4R. The use of the SCIM markers as a source of molecular markers
      that could be linked to interesting genes or other important agronomic traits is
      discussed.

PMID- 15954502
TI  - Cchobo, a hobo-related sequence in Ceratitis capitata.
AB  - A hobo-related sequence, Cchobo, with high similarity to the Drosophila
      melanogaster HFL1 and hobo108 elements was isolated from the medfly. Thirteen PCR
      derived clones, which share 97.9-100% DNA identity, were sequenced, seven of
      which do not show frame-shift or stop codon mutations in their conceptual
      translations. The consensus sequence has 99.7% DNA identity with the D.
      melanogaster hobo element HFLI. In a phylogenetic analysis with other hobo
      related elements, Cchobo clusters with the HFL1 and hobo108 elements from D.
      melanogaster and hobo-related elements from D. simulans, D. mauritiana and
      Mamestra brassicae. These elements may have undergone horizontal transfer in the
      recent past. The genomic distribution of Cchobo was studied by FISH to mitotic
      and polytene chromosomes, which revealed that Cchobo is distributed within both
      the heterochromatin and euchromatin. Intra- and interstrain polymorphisms were
      detected both at euchromatic and heterochromatic sites. These findings suggest
      that active copies of the element may be present in the medfly genome.

PMID- 15954503
TI  - Vive la difference!

PMID- 15954504
TI  - Technology at the crossroads with care and costs: the implantation of the
      automatic internal cardiac defibrillator.

PMID- 15954505
TI  - Physical function and quality of life in older adults: sex differences.

PMID- 15954506
TI  - Ejection fraction and QRS width as predictors of event rates in patients with
      implantable cardioverter defibrillators.
AB  - OBJECTIVES: The Multicenter Automatic Defibrillator Implantation Trial II in 2002
      recommended implantable cardioverter defibrillators (ICDs) prophylactically for
      all patients with a prior myocardial infarction and ejection fraction (EF) of 30%
      or less. In June of 2003, the Centers for Medicare and Medicaid Services approved
      reimbursement for ICD placement in patients with an EF of 30% or less who have a
      QRS interval greater than 120 ms. The purpose of this study was therefore to
      determine the value of QRS duration in predicting the occurrence of ventricular
      arrhythmias within the first year after ICD implantation. These ICDs were placed
      over the past 5 years for various indications. METHODS: EF cut points of 30% or
      less and 31% or greater and QRS duration of 120 ms or less and 121 ms or greater
      were used to assess the risk of events. RESULTS: There was a significant increase
      in events in subjects with EF of 30% or less, compared with patients with EF of
      31% or greater (P < 0.05), and there was a trend toward increased likelihood of
      arrhythmias in patients with widened QRS width. CONCLUSIONS: This study confirms
      the conclusion of the Multicenter Automatic Defibrillator Implantation Trial II
      and implies that the Centers for Medicare and Medicaid Services criteria for
      reimbursement may not be scientifically valid.

PMID- 15954507
TI  - Distribution of pleural effusion in congestive heart failure: what is atypical?
AB  - OBJECTIVES: This study was performed to determine the distribution of pleural
      effusion between the right and left hemithorax in patients with uncomplicated
      congestive heart failure, and to determine whether left-sided pleural effusion
      actually constitutes an atypical distribution in congestive heart failure.
      METHODS: The study group consisted of 120 consecutive patients with both clinical
      and radiographic evidence of uncomplicated congestive heart failure, and whose
      chest radiographs at the time of presentation also showed evidence of pleural
      effusion. The presence or absence of pleural effusion in the right and left
      hemithorax was recorded for each case, as was the size of each pleural effusion,
      and the distribution of pleural effusion in these 120 patients was entered into a
      2 x 2 table and analyzed by chi2 analysis. RESULTS: There were 207 total pleural
      effusions, with 105 on the right and 102 on the left. Isolated right-sided
      pleural effusions occurred in 18 patients, there were bilateral pleural effusions
      larger on the right than the left in 25, there were bilateral pleural effusions
      of roughly equal size on each side in 36, there were bilateral pleural effusions
      larger on the left side than the right in 26, and there were isolated left-sided
      pleural effusions in 15. The difference was not statistically significant (chi2 =
      0.316; P < or = 1.0). CONCLUSIONS: Left-sided pleural effusion is not an atypical
      finding in congestive heart failure and is not, in and of itself, an indication
      for further clinical or imaging evaluation.

PMID- 15954508
TI  - Does the use of standardized history and physical forms improve billable income
      and resident physician awareness of billing codes?
AB  - OBJECTIVES: Resident physician knowledge of financial reimbursement guidelines
      for patient encounters is limited. We determined whether the use of standardized
      history and physical examination forms by residents for hospital admissions plus
      a brief lecture would increase the level of billing codes, increase billable
      income, and increase resident awareness of billing guidelines. METHODS: Residents
      used history and physical examination forms after a brief documentation lecture.
      Pretrial and posttrial surveys measured awareness of billing guidelines. The
      admission billing codes for a 6-month period were obtained, and the percentages
      were compared with a control 6-month period. RESULTS: There was an absolute
      increase of 14.5% in the highest code between the two study periods (P < 0.0001).
      Billable income increased by $10,385. Resident documentation awareness also
      increased (P < 0.001). CONCLUSIONS: The use of history and physical examination
      forms, combined with a brief lecture, significantly increased the percentage of
      highest billing codes, which increased billable income. Resident awareness of
      documentation requirements significantly improved.

PMID- 15954509
TI  - Relation of residency selection factors to subsequent orthopaedic in-training
      examination performance.
AB  - OBJECTIVES: Orthopaedic surgery remains one of the most competitive specialties,
      with more than a 99% match fill rate in the past several years. An oversupply of
      qualified applicants leads to intense competition for these residency spots,
      allowing program directors to be more selective in choosing their future
      residents. Although many previous studies have documented factors important to
      program directors in the admission process, less is known about how preselection
      factors correlate with subsequent performance in a residency program. METHODS:
      The relation of both demographic and academic factors with subsequent performance
      on the Orthopaedic In-Training Examination (OITE) were studied. These factors
      include United States Medical Licensing Examination (USMLE) step I scores, Alpha
      Omega Alpha (AOA) status, research publications, age entering residency, marital
      status, and medical school affiliation. RESULTS: In this study, the only
      statistically significant correlations to OITE scores were USMLE step I
      performance and marital status. Those residents who had previously scored above
      220 on the USMLE step I had higher average OITE scores than those scoring below
      220. Residents who were married also had higher average OITE scores. A trend with
      regard to AOA status also was found, with residents scoring slightly higher on
      the OITE if they were members of AOA. CONCLUSIONS: Few preresidency variables
      correlate to success during an orthopaedic residency.

PMID- 15954510
TI  - Statin therapy in rheumatoid arthritis.
AB  - Rheumatoid arthritis, a chronic inflammatory polyarthritis that destroys synovial
      joints, is associated with systemic as well as local inflammation and with an
      increased risk of cardiovascular disease and death not fully explained by
      traditional cardiac risk factors. Statins (HMG-coA reductase inhibitors),
      medications originally designed to lower cholesterol, have been shown to have
      powerful effects on decreasing cardiovascular mortality rates in the general and
      high-risk populations. Not all of this protective benefit appears to be mediated
      by lowered cholesterol levels. Statins also influence multiple steps in the
      inflammatory process, including leukocyte migration and adhesion, T-cell
      stimulation, nitric oxide bioavailability, generation of free radicals, and
      angiogenesis. Recent studies show that statins may provide mild anti-inflammatory
      benefit in rheumatoid arthritis, in addition to reducing cardiovascular risk.

PMID- 15954511
TI  - Thyroid disorders in elderly patients.
AB  - Thyroid disorders are common in the elderly and are associated with significant
      morbidity if left untreated. Typical symptoms may be absent and may be
      erroneously attributed to normal aging or coexisting disease. Physical
      examination of the thyroid gland may not be helpful, as the gland is often
      shrunken and difficult to palpate. Usually only myxedema coma requires
      levothyroxine parenterally; all other forms of hypothyroidism can be treated with
      oral levothyroxine. Low-dose levothyroxine should be initiated and increased
      gradually over several months. In unstable elderly patients with hyperthyroidism,
      antithyroid medication can quickly produce a euthyroid state. Radioactive iodine
      therapy is more definitive and is well tolerated, effective, and preferred.
      Surgical thyroid ablation may be necessary in patients who fail to respond to
      radioactive iodine therapy and in patients with multinodular goiter. If there is
      a suspicion of malignant disease, early biopsy or fine needle aspiration for
      cytology should be considered.

PMID- 15954512
TI  - Abuse of supraphysiologic doses of anabolic steroids.
AB  - The following article is a literature review of supraphysiologic doses of
      anabolic-androgenic steroids (AAS). This article contains a brief review of the
      history of AAS, the chemistry of the varying forms of AAS, and proposed
      mechanisms of action. The article then focuses on how AAS are used in an illicit
      manner by the general population. Terms such as "stacking" and "pyramiding" are
      discussed. The article concludes by looking at the major detrimental side
      effects, such as liver damage and cardiovascular changes, which physicians may
      encounter when treating AAS abusers.

PMID- 15954513
TI  - Removal of vena caval filter at 224 days.
AB  - Patients at risk of pulmonary embolism usually receive anticoagulants, which are
      contraindicated in trauma victims. A woman with extensive deep venous thrombosis
      after a vehicle accident had a nitinol Recovery Filter inserted prophylactically.
      After her recovery, she requested filter removal because of her intention to
      become pregnant. The filter was removed percutaneously without difficulty 224
      days after implantation.

PMID- 15954514
TI  - Determining functional significance of subclavian artery stenosis using exercise
      thallium-201 stress imaging.
AB  - Subclavian artery stenosis (SAS) is a rare lesion accounting for nearly 2.5% of
      all extracranial arterial occlusions. Symptoms from SAS usually relate to
      subclavian steal, and include syncope, vertigo, ataxia, and, rarely, upper limb
      paralysis or hemipareses. Upper extremity ischemia may result in intermittent or
      constant arm pain. The majority of patients with SAS are asymptomatic. Upper
      extremity ischemia is particularly unusual. More commonly, patients with
      significant SAS have symptoms of cerebral ischemia, which are usually triggered
      by vigorous motion of the arm on the side of the severe proximal subclavian
      obstruction. Stress exercise radionuclide imaging appears to be a valuable
      modality in determining the functional significance of SAS. We describe a case in
      which radionuclide imaging with thallium-201 after stress of the upper
      extremities was used for risk stratification of subclavian stenosis, and to help
      decide treatment options.

PMID- 15954515
TI  - Ludwig's angina: an uncommon cause of chest pain.
AB  - A 71-year-old male with coronary artery disease, hypertension, diabetes mellitus,
      tobacco and opioid dependence came to the emergency room complaining of one
      episode of retrosternal chest pain oppressive in nature of one day of evolution.
      He had acute respiratory distress and required mechanical ventilation. The
      initial impression was myocardial ischemia, but electrocardiography and cardiac
      enzymes ruled it out. During the following hours, neck and tongue edema
      developed. He was started on broad-spectrum antibiotics empirically. Neck
      computed tomography scan revealed a left parapharyngeal and submandibular
      abscess. The abscess was drained. The source of infection was found on the second
      molar of the left lower jaw. The patient improved and was successfully weaned
      from mechanical ventilation. Despite advances in therapy, Ludwig's angina remains
      a potentially lethal infection in which early recognition plays a crucial role.

PMID- 15954517
TI  - Foix-Alajouanine syndrome: an uncommon cause of myelopathy from an anatomic
      variant circulation.
AB  - Foix-Alajouanine syndrome is a rare cause of myelopathy caused by dural
      arteriovenous malformation of the spinal cord, mostly lower thoracic and lumbar.
      Patients are usually over 50 years of age and can present with acute lower
      extremity dysesthesias or intermittent sciatica. Progression to paraplegia may be
      slow. Spinal angiography is needed for definitive diagnosis, based on the clues
      provided by the symptoms. If diagnosed early, vascular embolization or
      neurosurgical excision may be curative.

PMID- 15954516
TI  - Infliximab-induced headache and infliximab-induced meningitis: two ends of the
      same spectrum?
AB  - This report describes a case of aseptic meningitis induced by the tumor necrosis
      factor-alpha inhibitor infliximab. The patient, a 51-year-old female, was being
      treated for Crohn's disease. After an infliximab infusion, she had headache,
      fever, arthralgia, myalgia, and meningismus. Cerebrospinal fluid analysis was
      remarkable for a neutrophilic pleocytosis and elevated protein. Other potential
      causes of meningitis were excluded. Her symptoms completely resolved within 24
      hours of presentation. Because infliximab commonly causes headache and is very
      immunogenic, we infer that infliximab-induced meningitis is immune-mediated and
      underrecognized. Potential risk factors and means for minimizing its occurrence
      are offered.

PMID- 15954518
TI  - Sweet syndrome associated with furosemide.
AB  - This case report describes a case of Sweet syndrome (SS) related to use of
      furosemide in a 46-year-old female who was admitted for treatment of congestive
      heart failure. Three days after administration of furosemide, the patient had a
      fever and a skin eruption appeared on her wrists, forearms, and legs. Biopsy of
      the skin lesion was consistent with SS. Infection was thought to be unlikely
      because of negative blood cultures, echocardiography, and other imaging studies.
      Careful review of her medications revealed that the patient received furosemide
      before the appearance of the skin eruption and fever. After discontinuation of
      furosemide, the patient's skin lesion and fever resolved. A MEDLINE search from
      June 1966 to May 2004 revealed only one reference documenting the association of
      SS with furosemide administration. Patients who have development of SS without an
      obvious cause should have their medication list closely reviewed.

PMID- 15954519
TI  - Isolated intraperitoneal bladder rupture following minor trauma after alcohol
      ingestion.
AB  - The authors describe a case of intraperitoneal bladder rupture in a 41-year-old
      male caused by trauma from a fall after alcohol ingestion. The patient presented
      on the day following the fall with signs of acute urinary retention, and 500 mL
      of urine was drained after catheterization. Signs of peritonitis appeared on the
      following day, and emergency computed tomography revealed intraperitoneal
      rupture. Laparotomy revealed a laceration of the bladder in the fundus.

PMID- 15954520
TI  - Cronkhite-Canada syndrome with hypothyroidism.
AB  - Cronkhite-Canada syndrome is a rare, noninherited gastrointestinal polyposis
      syndrome associated with characteristic ectodermal abnormalities. This report
      describes a 60-year-old female who was diagnosed with Cronkhite-Canada syndrome
      with hypothyroidism after presenting with chronic diarrhea, alopecia,
      intermittent abdominal pain, generalized gastrointestinal polyposis,
      hyperpigmentation, and nail dystrophy. Endoscopic examination of the stomach and
      duodenum showed multiple sessile polyps and mucosal erosion associated with
      evidence of chronic inflammation. Colonoscopy also revealed mucosal edema and
      diffuse polyposis.

PMID- 15954521
TI  - Mastoiditis in an immunocompetent adult.
AB  - A 20-year-old white male presented to the family practice department with a 1
      month history of right ear pain and loss of hearing. During the month, he had
      been seen in emergency rooms twice and also by his dentist. He had been treated
      with pain medications, tooth extraction, and finally, antibiotics. On
      presentation to the clinic, his right mastoid area showed erythema, tenderness,
      and swelling that displaced the pinna. He was immediately referred to the
      otolaryngology department. Imaging studies confirmed coalescent mastoiditis and
      subperiosteal abscess. He was taken to surgery, where he underwent cortical
      mastoidectomy and right pressure equalization tube placement. Intraoperative and
      postoperative intravenous cefotaxime was given. Recovery was complete and
      uneventful.

PMID- 15954522
TI  - Effect of advanced age in subjective surgical outcome of patients undergoing
      spine surgery.

PMID- 15954523
TI  - Sclerosing hemangioma.

PMID- 15954524
TI  - Polymicrobial peritonitis including Pantoea agglomerans from teething on a
      catheter.

PMID- 15954525
TI  - Memories from my years in public practice.

PMID- 15954526
TI  - The patient's page.

PMID- 15954527
TI  - Formation of a parasitophorous vacuole in a nonadequate experimental host:
      electron microscopical and X-ray microanalytical study.
AB  - An unusual mechanism of formation of a parasitophorous vacuole as a result of
      interaction between an invasive stage of a parasite (merozoites of a protozoon,
      Mattesia dispora) and defense response of an insect host, Galleria mellonella is
      reported. The entire ontogenesis of parasitophorous vacuole can be divided into
      five morphologically clearly discernible stages. They differed, e.g., in the
      contents and distribution of elements at subcellular level, as determined by
      direct in situ elemental analysis of single organelles (electron microprobe X-ray
      analysis). The method was used in conjunction with electron microscopy to
      investigate the relationship between the host and the parasite.

PMID- 15954528
TI  - Properties of Saccharopolyspora erythraea strains after protoplast regeneration.
AB  - Protoplast formation, stabilization and regeneration was improved for 4 strains
      (erythromycin producers) of Saccharopolyspora erythraea. A modified medium was
      developed for protoplast regeneration. Parental and protoplast-regenerated
      strains exhibited changes in morphology, ultrastructure, and antibiotic
      production.

PMID- 15954529
TI  - Generation of landomycin D-producing strain Streptomyces globisporus LD3.
AB  - Rhodinosyl transferase gene lndGT4, governing the conversion of the disaccharide
      oligoketide ('polyketide') landomycin D into a trisaccharide derivative
      landomycin E, was deleted in Streptomyces globisporus 1912 genome. Possible
      resistance mechanisms that protect the resulting landomycin D-producing mutant
      strain S. globisporus LD3 against the toxic action of landomycins were
      determined.

PMID- 15954530
TI  - Lipid analysis of the plasma membrane and mitochondria of brewer's yeast.
AB  - The plasma membrane and mitochondria of bottom fermenting brewer's yeast obtained
      as a by-product of industrial beer production were isolated and the lipid
      fraction was analyzed. The phospholipid content accounted for 78 mg/g protein in
      the plasma membrane and 59 mg/g protein in the mitochondria. Major phospholipids
      in both preparations were phosphatidylinositol, phosphatidylcholine and
      phosphatidylethanolamine but their proportions differed significantly. In the
      plasma membrane phosphatidylinositol, and in the mitochondria phosphatidylcholine
      were present in the highest concentration (37 and 30%, respectively). The main
      classes of neutral lipids (triacylglycerols, ergosterol, squalene and steryl
      esters) were twice more abundant in the plasma membrane than in the mitochondria
      (61 and 33 mg/g protein, respectively). A characteristic of the neutral lipid
      composition of both organelles was the low content of ergosterol (12 and 7 mg/g
      protein, respectively) and a high content of squalene (25 and 22 mg/g protein).
      The main feature of the fatty acid composition of both organelles was the
      preponderance of saturated fatty acids (78 and 79%, respectively), among which
      palmitic acid was the principal one. The most expressed characteristics of lipid
      fractions of the analyzed plasma membranes and mitochondria, high concentration
      of squalene and preponderance of saturated fatty acids are the consequences of
      anaerobic growth conditions. The lack of oxygen had possibly the strongest effect
      on the lipid composition of the plasma membranes and mitochondria of bottom
      fermenting brewer's yeast.

PMID- 15954531
TI  - Improved method of detection and molecular typing of Borrelia burgdorferi sensu
      lato in clinical samples by polymerase chain reaction without DNA purification.
AB  - A simple assay by polymerase chain reaction was used for the of detection of
      Borrelia burgdorferi, causative agent of Lyme borreliosis (LB). It involves no
      DNA purification and is based on the amplification of a specific region of ospA
      gene of B. burgdorferi, followed by direct detection of the PCR product with SYBR
      Green I by agarose gel electrophoresis. The method was used to analyze samples
      from patients with LB diagnosis, with presumable infection with the LB
      spirochete, those with unclear clinical symptoms and after the course of an
      antibiotic treatment. Spirochetal DNA was detected by PCR even in contaminated
      samples in which B. burgdorferi was overgrown by fungi and other bacteria.
      Spirochetal DNA was detected and borrelia species was identified in cerebrospinal
      fluid of two patients hospitalized with the diagnosis "fever of unknown origin".
      Western blot and ELISA were negative in both cases. Total analysis of 94 samples
      from the hospital in Ceske Budejovice (South Bohemia, Czechia) showed infection
      with B. burgdorferi sensu stricto in 11% and B. garinii in 15% of cases. The
      highest prevalence was found for B. afzelii (43%). Co-infection was confirmed in
      24 % of the analyzed symplex; 7% of samples that were B. burgdorferi sensu lato
      positive gave no results in DNA amplification with B. burgdorferi sensu stricto-,
      B. garinii- and B. afzelii-specific primers. The proposed reliable, rapid,
      unexpensive and specific technique could form the basis of laboratory tests for
      routine detection and identification of Lyme-disease spirochete in different
      samples.

PMID- 15954532
TI  - Curli expression of enterotoxigenic Escherichia coli.
AB  - One hundred and four enterotoxin producing Escherichia coli strains of wide
      geographical origin were tested for the expression of curli fimbriae by
      transmission electronmicroscopy and by ELISA using curli-specific antibodies, as
      well as for the presence of curli-specific gene sequences by PCR. All isolates,
      irrespective of the production of the fimbriae, carried sequences specific for
      the structure (csgA) and for one of the regulator genes (crl) of curli
      expression, respectively. Curli fimbriae were detected in 56 strains (53.8 %).
      Thirty-six strains expressed curli only when growing at 30 degrees C, 4 isolates
      were weakly curliated at 37 degrees C only, while on 16 strains curli was
      observed at both temperatures. On isolates carrying curli at both temperatures
      the expression of the fimbria was significantly stronger at 30 degrees C than at
      37 degrees C. Curli proficiency significantly, but not completely, correlated
      with the binding of the Congo Red dye. The expression of curli did not confer
      epithelial cell invasiveness to ETEC strains but, once expressed at 30 degrees C,
      it facilitated the adherence of the bacteria to plastic surfaces. Curli present
      in more than half of the ETEC strains and expressed preferentially at low
      temperatures could be a factor facilitating the environmental survival of this
      food- and water-borne pathogen.

PMID- 15954534
TI  - Assessing the pathogenic effect of Fusarium, Geosmithia and Ophiostoma fungi from
      broad-leaved trees.
AB  - Phytopathogenic effect of Geosmithia pallida, G. langdonii, Ophiostoma
      grandicarpum, O. querci, two isolates of O. piceae, and two isolates of Fusarium
      solani was compared using plant growth test (stem and root length of garden cress
      plants seeded on mycelium-covered potato carrot agar); Ophiostoma spp. and F.
      solani were isolated from oak, Geosmithia spp. from galleries of Scolytus
      intricatus on beech. All fungi inhibited more the root elongation than that of
      stems. F. solani led to plant collapse after briefly stimulating the growth of
      stem and in one case also root. G. langdonii inhibited stem and root growth to
      20% and led to plant collapse. G. pallida inhibited root growth to 25% whereas
      stem growth was almost unimpaired. Ophiostoma spp. reduced stem growth to
      approximately 60-80% and root growth to 25-60%. O. piceae and O. querci caused
      plant collapse after 15-20 d.

PMID- 15954533
TI  - Characterization of the alternative sigma factor sigmaG in Streptomyces
      coelicolor A3(2).
AB  - Using the previously established two-plasmid system for the identification of
      promoters recognized by a particular sigma factor, we identified two positive DNA
      fragments that were active only after induced sigG, encoding sigma factor sigmaG
      of Streptomyces coelicolor A3(2). High-resolution S1-nuclease mapping in the
      Escherichia coli two-plasmid system identified potential promoters, PG45 and
      PG54, whose sequences were similar to the consensus sequence of Bacillus subtilis
      promoters recognized by the general stress-response sigma factor sigmaB. However,
      both putative sigmaG-dependent promoters were not active in S. coelicolor.
      Sequence analysis of the regions potentially governed by the promoters revealed a
      gene encoding a hypothetical protein SCO5555 and the rrnE gene encoding rRNA
      operon. To confirm that sigG encodes sigma factor, the sigmaG protein was
      overproduced in E. coli and purified. In an in vitro transcription assay, sigmaG,
      after complementation with S. coelicolor core RNA polymerase, was able to
      recognize both sigmaG-dependent promoters and initiate transcription.

PMID- 15954535
TI  - Quantitative analysis of streptococcal exoprotein flow to the host receptor-
      exact basis for therapy of tumors and Alzheimer's disease.
AB  - The basis of a bacterial pathogenic process consists in the change of a certain
      host structure to a completely different one. This is accomplished by binding of
      a bacterial protein product to the host structure. Streptococcal NAD+
      nucleosidase was explored as to its binding to the host receptor represented by
      beef heart extract. The bacterial product was found to bind to the host structure
      until the available host structure was fully saturated. The similarity of the
      above flows of macromolecules with some models of morphogenesis indicates the
      existence of diseases associated with the flow of a protein to the undesirable
      site in the organism. In such a case therapy with low-molar-mass substances is
      wrong in principle.

PMID- 15954536
TI  - Possible role of procathepsin D in human cancer.
AB  - For the past ten years, our research has been focused on elucidating the
      mechanism by which procathepsin D (pCD) impacts cancer development. Various
      studies have shown that pCD is overexpressed and secreted by numerous cancer cell
      lines. After secretion, it exhibits "growth hormone-like" activity on cancerous
      cells but the exact mechanism of this mitogenic activity is not yet understood.
      The activation peptide of pCD (APpCD) (which is cleaved off upon activation of
      the zymogen) is responsible for the mitogenic function of pCD. Various in vitro
      and in vivo studies support our theory that the APpCD interacts with both parent
      and neighborhood cancer cells and thus functions as an autocrine mitogen. We
      propose a model of pCD mitogenic function and also some possible approaches for
      treatment and prevention of certain types of cancer.

PMID- 15954537
TI  - Comparison of protective effect of protein and DNA vaccines hsp90 in murine model
      of systemic candidiasis.
AB  - Preventive vaccination by a hsp90-expressing DNA vaccine and recombinant hsp90
      protein vaccine, both derived from the Candida albicans hsp90 using BALB-c mouse
      model of systemic candidiasis, was performed. Hsp90 mRNA was cloned from a
      clinical isolate of C. albicans, converted to cDNA and cloned into vaccination
      plasmid pVAX1. Two methods of DNA application were tested: intramuscular (i.m.)
      and intradermal (i.d.) injection. Recombinant protein was applied by i.d.
      injection with Freund's adjuvant; the control groups received PBS or Freund's
      adjuvant only. Mice were vaccinated and after 19 d re-vaccinated. After 3 weeks,
      the mice were challenged with the live C. albicans in a dose of 5 x 10(6) CFU per
      mouse. After the challenge, the mice vaccinated i.d. with DNA vaccine survived
      for 39 and 64% longer compared to those receiving Freund's adjuvant and/or PBS,
      respectively. The i.m. application of the DNA vaccine did not provide any
      significant protectivity. The serum level of anti-candida-hsp90 serum IgG
      antibodies correlated with the survival rate in both i.d. protein and DNA
      vaccination approaches. We stressed the importance of specific humoral immunity
      in the mouse model of systemic candidiasis.

PMID- 15954538
TI  - Lipopolysaccharide-mediated protection against Klebsiella pneumoniae-induced
      lobar pneumonia: intranasal vs. intramuscular route of immunization.
AB  - Immunoprotective potential of delivered lipopolysaccharide (LPS) preparation from
      Klebsiella pneumoniae was determined in a murine model of lobar pneumonia.
      Protection was assessed with three doses of LPS (25, 50 and 100 microg; without
      any adjuvant) administered intranasally or intramuscularly. After evaluation of
      lung tissue (bacterial load and histopathology), no significant protection was
      observed at 25 microg with either application. A significant decrease in lung
      bacterial load coupled with fall in severity of lung lesions was observed with 50
      microg (again both applications). At 100 microg dose, with intramuscular route, a
      further decrease in the lung bacterial load was shown compared to the 50 microg
      dose. In contrast, 100 microg LPS, when given intranasally, resulted in a higher
      bacterial colonization of the lung tissue and higher lung pathology; thus we
      recommend intramuscular instead of the intranasal route for developing protection
      against K. pneumoniae-mediated pneumonia with intact LPS-based vaccines.

PMID- 15954539
TI  - Comparison of different tests to diagnose feline infectious peritonitis.

PMID- 15954540
TI  - Clostridium difficile-associated disease.

PMID- 15954541
TI  - Spontaneous hypoadrenocorticism in a dog after a diagnosis of
      hyperadrenocorticism.

PMID- 15954542
TI  - Potential for control of oxidative injury by administration of antioxidants in
      veterinary medicine.

PMID- 15954543
TI  - The effects of S-adenosylmethionine on clinical pathology and redox potential in
      the red blood cell, liver, and bile of clinically normal cats.
AB  - S-adenosylmethionine (SAMe), an important hepatic metabolite and glutathione
      (GSH) donor, has been studied mechanistically in vitro, in humans with clinical
      liver disease, and in experimental animal models of liver disease. Collective
      findings encourage its therapeutic use in necroinflammatory and cholestatic liver
      disorders. A chronic longitudinal study (pre- and posttreatment parameters
      compared) was undertaken with 15 clinically healthy cats given a stable 1,4
      butanedisulfonate (S'S isomer) SAMe salt (enteric coated tablets providing 180 mg
      SAMe), dosage 48 mg/kg PO q24h, on an empty stomach for 113 days. Routine
      physical and clinicopathologic assessments, red blood cell (RBC) osmotic
      fragility, liver function and histology, hepatic concentrations of reduced GSH
      (RGSH) and its oxidized disulfide form (GSSG), protein, glycogen, and
      deoxyribonucleic acid, GSH concentrations in RBCs, total bile acids in serum and
      bile, oxidative membrane products (TBARS) in RBCs and liver, and plasma SAMe
      concentrations were evaluated. SAMe administered PO significantly increased
      plasma SAMe concentrations, and peak concentrations usually occurred 2-4 hours
      after dosing. Chronic SAMe administration did not change peak or cumulative
      plasma SAMe concentrations and did not [corrected] cause overt signs of toxicity.
      A positive influence on RBC and hepatic redox status (RBC TBARS reduced 21.1% [P
      < .002], liver GSH increased 35% [P < .002], liver RGSH: GSSG ratio increased 69%
      [P < .03]) and improved RBC resilience to osmotic challenge (P < .03) were
      observed. Results prove that this SAMe PO product is enterically available and
      suggest that it imparts biologic effects that might be useful for attenuating
      systemic or hepatic oxidant challenge.

PMID- 15954544
TI  - Histopathologic features of canine uremic gastropathy: a retrospective study.
AB  - Uremic gastritis is a term commonly used to describe the gastrointestinal signs
      and histopathologic changes associated with renal failure in the dog. This
      retrospective study reviews the clinical, serum biochemical, and postmortem
      histopathologic data from 28 dogs with renal failure to determine the prevalence
      of gastric histopathology, characterize the gastric histopathology, and identify
      associations between gastric histopathology and serum concentrations of blood
      urea nitrogen (BUN), creatinine (Cr), calcium-phosphorus product (Ca x Phos), and
      hematocrit. Affected and control dogs with available renal and gastric tissue,
      serum biochemistry data, and urinalysis data were identified over a 10-year
      period (1992-2002) in the pathology department postmortem examination database at
      the Cornell University College of Veterinary Medicine. The serum biochemistry
      data and histopathologic findings were scored as normal, mild, moderate, and
      severe. All affected dogs had derangements of BUN, Cr, or Ca x Phos with gastric
      histopathology in 22 of 28 dogs (79%). Dogs with renal failure had a higher
      prevalence of gastric histopathologic changes compared with the control group.
      Associated histopathologic changes in the stomach were edema (P = .008),
      mineralization (P = .03), and vasculopathy (P = .03). Only 1 dog had evidence of
      gastric ulceration. Gastric necrosis was an uncommon finding (4/28, 14%). Gastric
      histopathology appears to be common in dogs with renal failure and is associated
      with increasing severity in the serum biochemistry data. Unlike humans with renal
      failure, in whom gastric ulceration predominates, gastric necrosis and ulceration
      appear to be uncommon in dogs with renal failure.

PMID- 15954545
TI  - Inherited congenital extrahepatic portosystemic shunts in Cairn terriers.
AB  - The pathogenesis of congenital portosystemic shunt (CPSS) in dogs still is
      incompletely understood. In Irish Wolfhounds and Yorkshire Terriers, CPSS is
      reported to be hereditary. The aim of this study was to investigate a possible
      genetic basis and the mode of inheritance of CPSS in Cairn Terriers. Between July
      1990 and July 2001, 6-week-old pups of the Dutch Cairn Terrier population were
      screened by measuring venous ammonia concentrations and in the presence of
      hyperammonemia by ultrasonography, autopsy, portal vein angiography, or
      exploratory celiotomy. The same successfully operated female was used 3 times in
      test matings with an unrelated affected male, her unaffected sire, and an
      affected offspring. The prevalence of CPSS in the general Cairn Terrier
      population, the direct progeny of frequently used males, and the offspring of the
      test matings were tested for significant differences. In total, 6,367 Cairn
      Terriers were screened; 32 males and 26 females had CPSS. In 3 large family
      groups, significantly higher prevalences were found compared with the general
      population (P < .0001, P < .0001, and P < .044). The prevalence of CPSS in the
      offspring of the test matings was significantly higher (P < .002) than in the
      general population. No sex predisposition occurred among the affected dogs. The
      higher prevalence of CPSS in the test matings and the 3 family groups compared
      with the general population indicates that CPSS in Cairn Terriers is a genetic
      disease. The inheritance is autosomal and most likely polygenic or monogenic with
      variable expression.

PMID- 15954546
TI  - Sideroblastic anemia in 7 dogs (1996-2002).
AB  - Sideroblastic anemia is an anemic condition characterized by chronic hypochromic
      anemia and the presence of large iron deposits in erythroid cells. Seven dogs
      with sideroblastic anemia were evaluated retrospectively. Historical, clinical,
      and clinicopathologic findings were reviewed to determine whether the condition
      was idiopathic or associated with disease conditions or drug or toxin exposure.
      Associated diseases were identified in 6 affected dogs and included acute
      hepatitis, pancreatitis, acute hepatitis and pancreatitis, inflammatory disease,
      glomerulonephritis, and myelofibrosis. None of the dogs had a history of recent
      exposure to drugs or toxins. One dog had no evidence of associated disease.
      Regardless of the associated disease condition, sideroblastic anemia was
      characterized by moderate to severe nonregenerative and frequently hypochromic
      anemia with prominent dysplastic features in bone marrow that were most prominent
      in the erythroid series. Survival varied from days to years. Identification of
      large numbers of siderocytes or sideroblasts in blood or bone marrow is
      inconsistent with a diagnosis of iron deficiency and should prompt a search for
      inflammatory disease conditions, including hepatitis, pancreatitis, and
      glomerulonephritis.

PMID- 15954547
TI  - Feline lymphoma in the post-feline leukemia virus era.
AB  - Lymphoma (lymphosarcoma or malignant lymphoma) is the most common neoplasm of the
      hematopoietic system of cats and reportedly the cat has the highest incidence for
      lymphoma of any species. A 21-year retrospective survey of feline lymphoma
      covering the period 1983-2003 was conducted with the patient database at the
      Veterinary Medicine Teaching Hospital (VMTH) at the University of California,
      Davis, School of Veterinary Medicine. This period comprises the post-feline
      leukemia virus (FeLV) era. Feline lymphoma historically has been highly
      associated with retrovirus infection. Mass testing and elimination and quarantine
      programs beginning in the 1970s and vaccination programs in the 1980s
      dramatically reduced the subsequent FeLV infection rate among pet cats. The
      results of this survey confirm a significant decrease in the importance of FeLV
      associated types of lymphoma in cats. In spite of this decrease in FeLV
      infection, the incidence of lymphoma in cats treated at the VMTH actually
      increased from 1982 to 2003. This increase was due largely to a rise in the
      incidence of intestinal lymphoma, and to a lesser degree, of atypical lymphoma. A
      high incidence of mediastinal lymphomas in young Siamese or Oriental breeds also
      was observed, supporting previous studies. Associations of intestinal lymphoma
      and inflammatory bowel disease and diet should be further considered.

PMID- 15954548
TI  - Synovial fluid changes in induced infectious arthritis in calves.
AB  - The objective was to develop an experimental model of septic arthritis in calves
      and to evaluate the effect of treatment on cytologic and bacteriologic variables
      of synovial fluid. The right tarsus of 7 healthy Holstein bull calves were
      inoculated with 10(8) colony-forming units of viable Escherichia coli of a pap
      positive strain (day 1). On day 2, joint lavage was performed and antibiotic
      treatment was instituted. Cytologic examinations, bacterial cultures, and pap
      factor determinations by polymerase chain reaction (PCR) were performed on
      synovial fluid samples that were collected daily until day 4, then every 4 days
      until day 24. Results of physical examination, the severity of lameness, and
      swelling were recorded. Clinical signs of septic arthritis appeared on day 2 and
      persisted until day 9 for all calves. Bacterial cultures from all calves were
      positive for E. coli on day 2, and remained positive until day 3 for 1 calf and
      until day 4 for 5 calves. In addition, PCR results were positive for all calves,
      with 6 positive through day 3 and 1 positive through day 4, after which a
      positive result was again obtained on day 24. Synovial fluid neutrophil counts
      and white blood cell counts were significantly increased on days 2-4; however,
      synovial total protein concentrations were increased (P < .05) throughout the
      experiment in comparison to day 1. Results of all bacterial cultures were
      negative on day 8, although clinicopathologic signs of inflammation persisted
      until day 20. This model successfully induced acute septic arthritis in calves.
      Rapid recovery occurred within 1 week when an appropriate treatment was
      instituted early in the course of the disease.

PMID- 15954549
TI  - Acute hemoperitoneum in horses: a review of 19 cases (1992-2003).
AB  - The medical records of 19 horses with acute hemoperitoneum were reviewed. The
      causes for the hemoperitoneum were idiopathic (8 horses), splenic hematoma with
      capsular tear (7), bleeding from the reproductive tract (3), multicentric
      hemangiosarcoma (1), and systemic amyloidosis (1). The affected horses were
      between 4 and 32 years of age (median 11.5 years). The most consistent findings
      on initial examination were depression, tachycardia, tachypnea, pale mucous
      membranes, prolonged capillary refill time, colic, and abdominal discomfort. Less
      common clinical signs included abdominal distention, profuse sweating, ataxia,
      and broad ligament mass palpated on rectal examination. Clinicopathologic
      abnormalities commonly detected were anemia, neutrophilia, lymphopenia,
      thrombocytopenia, hypoproteinemia, hypocalcemia, azotemia, increased creatinine
      kinase, and sorbitol dehydrogenase activity. Hemoperitoneum was diagnosed on the
      basis of abdominocentesis, transabdominal ultrasonography, and postmortem
      examination. Sixteen horses were treated, and 3 horses were euthanized at owners'
      request because of severe clinical signs. The treatment consisted of the
      administration of intravenous fluids, plasma or blood transfusion, nonsteroidal
      drugs, antimicrobial drugs, and antifibrinolytic and procoagulant agents. Rapid
      clinical deterioration was observed in 2 horses, necessitating euthanasia. The
      remaining 14 horses survived the abdominal bleeding (survival rate 74%) and were
      discharged 3-15 days (median 7.0 days) after presentation. Postmortem examination
      of the 6 nonsurvivors showed massive abdominal hemorrhage from splenic hematoma
      with capsular tear (2 horses), multicentric hemangiosarcoma with liver rupture
      (1), systemic amyloidosis with splenic hematoma and capsular tear (1), and
      bilateral ruptured ovarian hematomas (1). In one horse, no origin of the bleeding
      could be determined during postmortem examination.

PMID- 15954550
TI  - The use of sarmazenil in the treatment of a moxidectin intoxication in a foal.

PMID- 15954551
TI  - Unique radiographic appearance of bone marrow metastasis of an insulin-secreting
      beta-cell carcinoma in a dog.

PMID- 15954552
TI  - Hyperaldosteronism and hyperprogesteronism in a cat with an adrenal cortical
      carcinoma.

PMID- 15954553
TI  - Platelet function defect in a thoroughbred filly.

PMID- 15954554
TI  - Malignant hyperthermia in a horse anesthetized with halothane.

PMID- 15954555
TI  - Semilobar holoprosencephaly in a Morgan horse.

PMID- 15954556
TI  - Spinal cord granuloma due to Coccidioides immitis in a cat.

PMID- 15954557
TI  - Assessment and management of proteinuria in dogs and cats: 2004 ACVIM Forum
      Consensus Statement (small animal).
AB  - Emerging data indicate that more attention should be given to the detection,
      evaluation, monitoring, and treatment of dogs and cats with proteinuria. The
      purposes of this consensus statement are to describe an appropriate approach for
      accomplishing these tasks and to provide specific recommendations for assessing
      and managing dogs and cats with proteinuria based on data that are currently
      available. Because proteinuria and albuminuria have numerous possible causes,
      they must be assessed appropriately to determine their implications for the
      patient. This assessment involves localization of the origin of the proteinuria
      as well as determination of its persistence and magnitude. Because persistent
      renal proteinuria usually indicates presence of chronic kidney disease, which
      sometimes is a progressive disorder, its detection identifies dogs and cats that
      have increased risk for adverse health outcomes. Thus, urine testing that will
      detect proteinuria should be a component of the clinical evaluations of dogs and
      cats under all circumstances that prompt their veterinarians to also perform
      comprehensive hematologic and serum biochemical evaluations. At a minimum, this
      testing should consist of a complete urinalysis that includes a satisfactorily
      accurate semiquantitative test for protein, and positive reactions should be
      properly followed with further testing. The appropriate response to persistent
      renal proteinuria depends on the magnitude of proteinuria and the status of the
      patient. The recommended response generally involves continued monitoring,
      further investigation, and therapeutic intervention, which should be implemented
      as an escalating series of inclusive, stepwise responses.

PMID- 15954558
TI  - The European biotechnology funding map.
AB  - Biotechnology is an industry with very strong links to basic science. Therefore,
      the commercialisation of biotechnology draws heavily on public funded research.
      All European countries have developed policies to support biotechnology. This
      contribution gives an overview of public funding activities in all European
      member states during the 90s and identifies the biotechnology areas which
      received funding in the different countries. About 50% of all funds were
      channelled to biomedical research. Plant biotechnology, industrial biotechnology,
      and the cell factory were other important targets of public funding. Other fields
      such as animal biotechnology, environmental biotechnology, and non-technical
      areas of biotechnology were largely ignored by public funding in most European
      countries. Future funding trends indicate that this pattern will be mainly
      preserved.

PMID- 15954559
TI  - New experimental and theoretical tools for metabolic engineering of micro
      organisms.
AB  - Presently an increasing gap is developing between our experimental capabilities
      in metabolic engineering of microbial metabolism and our quantitative theoretical
      understanding of the kinetic interaction between primary metabolism and product
      pathways. Such theoretical understanding is absolutely needed for a rational
      design of said metabolic engineering experiments and targets. To obtain such
      understanding in-vivo kinetic experiments and in-vivo kinetic models are needed.
      To this end the following new methods for in-vivo kinetic studies of
      Saccharomyces cerevisiae have recently been developed. The Bioscope device allows
      the reliable and repeated perturbation (e.g. glucose pulse, or inhibitor etc.) of
      steady state biomass outside the fermentor and subsequent sampling and quenching
      to measure glycolytical intermediates and nucleotides in a time frame of 0-70
      seconds. Dynamic modelling of fermentor off-gas O2/CO2-measurements allows to
      calculate O2 uptake and CO2 production rates in such a perturbation experiment (0
      70 seconds time windows). A new LC-MSMS based method has been developed to
      measure large sets of intracellular metabolites in said in-vivo kinetic
      experiments. It has been shown for the first time that in long chemostat
      cultivation (up to 800 hrs.) intracellular metabolites levels drop, showing
      absence of a real steady state. A new kinetic format, lin log kinetics, has been
      developed for describing the intracellular kinetic behavior of metabolic
      networks. This format allows general analytical solutions of networks flux,
      metabolic levels. From simulation studies it appears that this approach is
      remarkable accurate in describing intracellular metabolite dynamics and in
      metabolic design questions of where to change enzyme levels and how much to
      achieve a desired change in fluxes and metabolite levels. At this moment these
      tools are being applied in metabolic engineering studies of Saccharomyces
      cerevisiae and Penicillin chrysogenum.

PMID- 15954560
TI  - Biotechnology and the consumer.

PMID- 15954561
TI  - Development of molecular monitoring methods for the evaluation of the activity of
      sulfate- and metal reducing bacteria (SMRBS) as an indication of the in situ
      immobilisation of heavy metals and metalloids.
AB  - Sulfate- and metal reducing bacteria (SMRBs) are known for their capacity to
      reduce and precipitate heavy metals and metalloids (HMM) as metalsulfides
      (Luptakova A et al, 1998), which have the characteristic of forming stable
      precipitates due to their very low solubility product. Therefore, we examined the
      potential of using the activity of SMRBs to create a bioreactive zone or barrier
      for the in situ precepitation of heavy metals as a remediation strategy for heavy
      metal contaminated groundwater. In order to obtain insight in the ongoing
      biological processes for using this information to direct or optimize the in situ
      HMM- precipitation process, a monitoring strategy for sulfate- reduction activity
      of SMRBs must be designed using molecular methods. Here, we report the results of
      batch and column experiments which demonstrate the feasibility to stimulate the
      endogenous SRB- population, resulting in the in situ precipitation of HMM as
      sulfide complexes. Moreover, the sustainability of the in situ HMM precipitation
      wa s shown. For the development of molecular monitoring methods, the community
      structures of different bacterial consortia, obtained from bioreactors, was
      analysed by shotgun cloning of total community DNA followed by sequencing of the
      16S rRNA- gene. The SRB- specific 16S rRNA- primerset SRB385R- 907F was used but
      this specificity to specifically amplify the 16S rRNA- gene of SRBs was low.
      Also, the dsr (dissimilatory sulfite reductase)- gene specific DSR1F- DSR4R
      primerset showed sometimes after amplification of the dsr- genes as part of the
      community structure analysis satellite bands on agarose gel. Present work is
      concentrating on the isolation and identification of SRB- strains in the
      different bacterial cultures. Shotgun cloning of the 16S rRNA- and dsr- gene of
      the strains and total community DNA will give the information that is necessary
      for the optimization of existing SRB- specific primers and design of new primers.
      These primers will be used for the development of monitoring techniques.

PMID- 15954562
TI  - Start-up and long-term performance of a gas phase biofilter packed with an inert
      carrier.
AB  - Several parameters affecting the performance and characteristics of alkylbenzene
      fed biofilters were checked when using perlite as inert carrier material. The
      influence of the inoculum on startup and long term performance was studied using
      both non defined as well as defined cultures. The inoculated pure cultures, which
      were still detected in the biofilter after several months operation, allowed
      shortening the start-up period Qualitative and quantitative biomass distribution
      appeared to be uneven along the biofilter bed in long term operation studies. The
      biofilter could withstand a drying period of several weeks although such
      operating condition led to a shift in dominant microbial populations in the
      biofilm which was followed by an increase of the biofilter performance. Although
      a water content of 55-60% appeared to be optimal with perlite, peformance data
      were still satisfactory down to a water content around 35-40%.

PMID- 15954563
TI  - Efficient control of activated sludge filamentous bulking by means of a multi
      component additive.
AB  - A multi-component additive formulated for a more efficient control of activated
      sludge filamentous bulking was evaluated at a full-scale treatment plant
      experiencing a severe filamentous bulking. It was found that, besides offering an
      immediate improvement of sludge settling, the multi-component additive was able
      to eliminate the filamentous bacteria causing the bulking. Hence, contrarily to
      ordinary additives, this novel additive yielded immediate as well as long-term
      improvement of sludge sedimentation upon a few additions.

PMID- 15954564
TI  - Towards on-line quantification of flocs and filaments by means of image analysis
      for optimization and control of activated sludge plants.
AB  - One of the main reasons for failing of the sedimentation process in activated
      sludge waste water treatment systems is filamentous bulking. This is a problem of
      world-wide nature that occurs when the ratio of filamentous to floc forming
      bacteria is too large. A fully automatic image analysis method for recognizing
      flocs and filaments in an activated sludge sample is presented. Computer
      generated images of flocs and filaments, as well as images of activated sludge,
      are used to assess the capability of simple shape descriptors to distinguish
      between flocs and filaments. Five different shape descriptors are scrutinized,
      three of which are derived from size descriptors, namely, the aspect ratio, the
      roundness, and the form factor. The fractal dimension and the reduced radius of
      gyration complete the list. The results yield that the form factor is the least
      suitable and the reduced radius of gyration is the most suitable shape descriptor
      to accurately identify flocs and filaments in a random activated sludge sample.
      Based on this, the ratio of flocs to filaments can be estimated automatically.
      Furthermore, it is proposed that by combining this information with a total
      biomass concentration measurement, the individual concentrations of flocs and
      filaments can be determined. Consequently, the method presented may form the
      basis for a sensor that acts as an early warning system for filamentous bulking.

PMID- 15954565
TI  - Enhanced sludge dewatering by electrofiltration. A feasibility study.
AB  - Sludge treatment is a major issue in today's waste water treatment. One of the
      problems encountered is the limiting dewaterability of mainly biological sludges,
      causing high final treatment costs for incineration or landfill. Although during
      recent years, improvements are realised in the field of dewatering, the actual
      dry solids content after dewatering remains at a maximum value of about 35%. In
      order to increase the dry solids content, the technique of electrofiltration was
      investigated. Electrofiltration is the combination of two known techniques,
      traditional pressure filtration and electroosmotic/electrophoretic dewatering.
      Pressure filtration is based on pressure as the driving force for dewatering a
      sludge. Limitations hereby lie in the clogging of the filter cloth due to the
      build-up of the filtercake. Electroosmotic/electrophoretic dewatering is based on
      an electric field to separate sludge colloid particles from the surrounding
      liquid by placing the sludge liquor between two oppositely charged electrodes. In
      this case, mobile sludge particles will move to one electrode due to their
      natural surface charge, and the liquid phase will be collected at the oppositely
      charged electrode. Combination of both techniques makes it possible to create a
      more homogeneous filter cake and prevent the filter from clogging, resulting in
      higher cake dry solids contents and shorter filtration cycles. To investigate the
      feasibility of this technique for the dewatering of activated sludge, a filter
      unit was developed for investigations on lab scale. Multiple dewatering tests
      were performed in which the electric parameters for electrofiltration were
      varied. It was derived from these experiments that very high filter cake dry
      solids contents (to more than 60%), and short filtration cycles were attainable
      by using a relatively small electric DC field. The power consumption was very low
      compared to the power needed to dewater sludge by thermal drying techniques. For
      this reason, this technique seems very promising for the dewatering of biological
      sludges.

PMID- 15954566
TI  - Use of a nitrifying culture to shorten the activation time of biofilters for the
      removal of ammonium and nitrite in freshwater aquaria.
AB  - The removal of ammonia (NH3) through nitrification in intensive aquaculture
      systems is an important process as the total ammonia nitrogen (TAN, compromising
      NH4+ and NH3) concentration often is the key limiting water quality parameter in
      these intensive aquaculture systems. In this study, the performance
      characteristics of a suspension of nitrifying cells (named ABIL) have been
      explored This aqueous suspension contains a highly active, nitrifying microbial
      consortium and is stable for several months when preserved at 4 degrees C. Tests
      were performed in freshwater at lab scale (70 L, 20 - 24 degrees C). Results
      showed that the application of the consortium at a dose of 5 mg Volatile
      Suspended Solids (VSS) L(-1) assures a total removal of ammonium and nitrite
      species from 10 mg N L(-1) to below the detection limit within a period of four
      days. Experimentally, at a substrate level of 10 mg TAN L(-1), a rate of
      biological ammonium and nitrite conversion of the order of 0.3 - 0.5 g TAN g(-1)
      VSS(-1) d(-1) could be achieved by the consortium in the freshwater aquaria
      systems tested Provided adequate aeration and dissolved oxygen levels of 6 mg per
      L or more, no important intermediary nitrite concentrations were noticed Only a
      small amount of TAN was not found back as nitrate and might have been lost due to
      ammonia stripping After 12 months preservation of the inoculum at 4 degrees C, no
      important decrease in ammonium removal activity and only a minor decrease in the
      nitrite removal rate of the consortium were noticed.

PMID- 15954567
TI  - Membranebioreactor with external membranes.
AB  - The recent development of less expensive and more performant ultrafiltration
      membranes has generated a new concept in biological treatment known as membrane
      bioreactors (MBR). In the field of wastewater treatment, the MBR process is used
      as a modification of the conventional activated sludge (CAS) process, where the
      clarifier is replaced by a membrane module for the separation of the solid and
      the liquid phase. Membrane technology can, amongst others, be applied for the
      fast retrofit of relatively high loaded activated sludge systems to nutrient
      removal. In the last year Aquafin has built up extensive experience with
      submerged membrane systems. The research presented here was aimed at evaluating a
      particular external tubular membrane unit for MBR. More specifically it was
      evaluated whether higher stable flux levels could compensate the higher energy
      consumption, typical for external membrane systems. Both (1) treatment
      performance and (2) possible operational drawbacks were tested on a 5 m3/h
      activated sludge pilot-scale. The membrane bioreactor was tested in parallel with
      a conventional activated sludge system.

PMID- 15954568
TI  - Re-use of biologically treated wastewater of a brewery.
AB  - Despite excessive rainfalls, Flanders is dealing with a water deficiency. A
      rational use of water is a necessity. Apart from the prevention principle, the re
      use of biologically treated wastewater (bio-effluent) is increasingly considered.
      From earlier research it is known that reverse osmosis (RO) is necessary for the
      elimination of salts and low molecular compounds from the bio-effluent. A
      thorough pretreatment is necessary to remove drastically the suspended solids,
      which are harmful to the reverse osmosis modules. This case study describes the
      experiments performed by SEGHERSbetter technology for Water N.V. on the treatment
      of wastewater effluent from a brewery. A comparative study between sand
      filtration (SF), in-line coagulation with sand filtration and ultrafiltration
      (UF) as a pretreatment was made. UF proved to be the best pretreatment for RO for
      the treatment of brewery bio-effluent. Finally, an economic evaluation of the
      membrane system (UF followed by RO) was made. The calculated total cost for the
      system is 0.26 Euros per m3 produced water. Investment costs and operation cost
      are also discussed.

PMID- 15954569
TI  - Renovation of the WWTP hove.
AB  - The provision of reliable treatment has always been a priority in sanitary
      engineering. However, there is an ever-increasing pressure to meet desirable
      standards at reduced costs. This paper sets out a methodology to enhance the
      likelihood of a satisfactory allocation of the resources while providing reliable
      treatment. The procedure was gradually developed to optimise the massive capital
      investment of the Flemish Government to comply with the effluent standards set in
      the EU Directive 271/91. The methodology makes an extended use of dynamic
      modelling. To facilitate the identification and estimation of the uncertainty, a
      probabilistic Monte Carlo engine is coupled to the dynamic models. In doing so
      this approach provides a way of explicitly incorporating uncertainty and
      variability in the process analysis. The procedure is examined in an upgrade of a
      conventional WWTP towards stricter effluent norms on nutrients. The results
      suggest that the procedure can support the decision-making process under
      uncertainty conditions and enhance the likelihood of meeting effluent standards
      not entailing above-normal capital investments. The analysis led to reducing the
      capital investment by 43%, producing savings of more than 1.2 million Euros.

PMID- 15954570
TI  - A new process for integrated treatment of industrial wastewater at municipal
      wastewater treatment plants.
AB  - A new process for integrated treatment of industrial wastewater at a municipal
      WWTP is presented. The process uses the ability of heterotrophic bacteria of
      rapid substrate uptake and storage. The excess sludge from the municipal
      treatment line is fed to a contact tank, which receives the industrial wastewater
      via a separate pipeline. The contact tank is aerated to such a degree that
      secures complete substrate uptake but minimises oxygen consumption due to instant
      substrate degradation. The sludge from the contact tank is mechanically pre
      thickened and then fed to an anaerobic digester. Hence, the major portion of the
      incoming COD load of the industrial wastewater is transferred to the anaerobic
      digester, where it contributes to an increased biogas production. The back load
      of the industrial wastewater treatment process to the municipal treatment line is
      very low.

PMID- 15954571
TI  - Mesophilic and thermophilic biological post treatment of anaerobic pretreated
      paper process water in a closed cycle paper mill.
AB  - Thermophilic treatment systems are gaining more and more interest due to
      increasing system closure and higher process water temperatures. The use of
      activated sludge as a suitable post treatment system for anaerobically pretreated
      paper process was studied at 30 and 55 degrees C. Two lab-scale plug flow
      activated sludge reactors were run in parallel for 6 months at 30 and 55 degrees
      C. Both reactors were operated simultaneously at a 20, 15 and 10 days SRT. The
      effects of temperature and SRT on sludge settleability and COD removal
      efficiencies of different fractions were studied. Total COD removal percentages
      over the whole experimental period were 58 +/- 5% at 30 degrees C and 48 +/- 10%
      at 55 degrees C. The effect of the SRT on the total COD removal was negligible.
      Differences in total COD removal between both systems were due to a lesser
      removal of soluble and colloidal COD at 55 degrees C compared to the reference
      system. Two major characteristics of the thermophilic reactor were: 1. a lesser
      removal of soluble COD compared to the mesophilic reactor and 2. a turbid
      effluent compared to the mesophilic reactor. Thermophilic effluent turbidity was
      caused by a combination of influent colloidal particles that were not effectively
      retained in the sludge flocs and an erosion of thermophilic activated sludge
      itself, as shown by DGGE profiles. DGGE patterns of mesophilic sludge differed
      from the thermophilic sludge indicating that different microbial communities were
      present in both reactor systems.

PMID- 15954572
TI  - Bioelectrosynthesis of organic chemicals and fuels.

PMID- 15954573
TI  - Anaerobic treatment of brewery wastewater with an internal membrane bioreactor.
AB  - Anaerobic treatment is growing very popular these days because of low sludge
      production compared to activated sludge processes. The drawback of the process is
      the risk of sludge washout, especially when the formation of granular sludge is
      not expected. By using an internal anaerobic bioreactor this problem can be
      overcome. A lab scale internal anaerobic membrane bioreactor was operated at
      SEGHERSbetter technology for Water N.V. to which brewery wastewater was fed
      (COD=2300 mg/l). Hollow fibres were inserted into the anaerobic bioreactor, from
      which the effluent was extracted by underpressure. The COD-removal was excellent
      and very constant at a value of 95%. No suspended solids were present in the
      effluent. The membrane permeability stabilised at relatively low value of 18
      l/m2.h.bar due to an irreversible adhesion of constituents in the bioreactor. No
      growth of biomass was found during two months of operation. Inocculated granular
      sludge fell apart into loose flocs within several weeks of the startup, not
      affecting biological performance. The internal anaerobic membrane bioreactor is a
      promising new area within the field of wastewater treatment. It is expected that
      this process will have an important future.

PMID- 15954574
TI  - Wastewater treatment with the internal MEMBIOR.
AB  - At SEGHERSbetter technology for Water n.v., an internal aerobic membrane
      bioreactor was developed with submerged flat membrane plates: the internal
      MEMBIOR. This system has several advantages compared to a conventional wastewater
      such as: compactness, reduced sludge production and very high effluent quality.
      Both laboratory and pilot scale installations are available for respectively
      feasibility and on-site pilot tests. The data obtained from these pilot tests
      allow an optimal design and dimensioning of the MEMBIOR technology, resulting in
      proper investments cost with guarantees and performance. Research on the internal
      MEMBIOR technology is based upon biological and membrane performance, aeration
      linked aspects and sludge morphology. A brewery bio-effluent was obtained using
      an internal MEMBIOR superior to a conventional wastewater treatment plant,
      absolutely free of suspended solids. A significant shift in sludge morphology
      over time was observed. Lower oxygen transfer coefficients were found when the
      sludge concentration increased, giving rise to the need for an additional
      aeration. Membrane performance was enhanced using an additional module aeration
      system.

PMID- 15954575
TI  - Assessment of the fouling potential of wastewater treatment plant effluent using
      a modified capillary suction time measurement.
AB  - A new technique was developed to measure membrane fouling, which is derived from
      the capillary suction time (CST)--a parameter often used to indicate the
      dewaterability of sludge--and which is called the modified CST (CSTm). The
      results indicate a good repeatability and reproducibility of the test. Spiking
      tests with suspended solids and humic acid, which have a high fouling potential,
      resulted in a significant rise of the CSTm value, indicating a sensitive
      assessment of these fouling components. However, the CSTm measurement is mainly
      indicative for the colloidal fouling of the sample.

PMID- 15954576
TI  - Optimisation of the discrete conductivity and dissolved oxygen monitoring using
      continuous data series obtained with automated measurement stations.
AB  - During the last five years, research on the relation between pollution loads and
      ecological river water quality has been done on the Dender river. In addition to
      biological sampling of macroinvertebrates and fish, automated measurement
      stations were used too to investigate the spatio-temporal variability of physical
      chemical water pollution. This study on on-line water quality data collection is
      based on a measurement campaign during March-April 2000 with two automated
      measurement stations at two different sites: the flow control weirs at
      Geraardsbergen and Denderleeuw. These measurement stations contain sensors for
      temperature, turbidity, conductivity, pH, redoxpotential and dissolved oxygen.
      Short wave radiation as well as rainfall were monitored by means of pyranometers
      and rain gauges. A refrigerated sampler with 24 bottles allowed to take samples
      for additional laboratory analyses. In this study, continuous measurements of two
      physical-chemical parameters, conductivity and dissolved oxygen, were analysed to
      evaluate the adequacy of the current monitoring frequency in Flanders. Analysis
      showed that discrete conductivity measurements can be sufficient for trend
      detection, but the measuring frequency must be highly increased from one
      measurement per month to at least 8 measurements. Continuous measurements for
      conductivity are preferred because extreme values are obtained as well. For
      dissolved oxygen, a single measurement per month in not enough. The percentage of
      dissolved oxygen showed a strong diurnal variation with maxima in the late
      afternoon (photosynthesis) and minima at night (respiration). This parameter also
      differed significantly from day to day. Continuous measurements are therefore
      necessary for a reliable assessment of the dissolved oxygen budget of surface
      waters. When using discrete measurements for dissolved oxygen, a set time should
      be introduced to eliminate diurnal variation.

PMID- 15954577
TI  - Carbon, nitrogen and phosphorus removal in a sequential batch reactor operated
      with high frequency oxygen oscillations.

PMID- 15954578
TI  - In situ bioremediation of soil contaminated with oil and heavy metals.
AB  - An experimental plot of soil contaminated with crude oil and heavy metals
      (copper, zinc and cadmium) was subjected to bioremediation using the activity of
      the indigenous soil microflora. The oil was light, rich in paraffins and with a
      very low content of asphaltene-resinous substances. Copper, zinc and cadmium were
      present mainly as sulfide minerals but also in forms more amenable to biological
      and chemical leaching. Their contents in the soil exceeded approximately 1.5-3
      times the relevant permissible levels. The soil microflora contained different
      oil-degrading and metal-solubilizing microorganisms. The activity of this
      microflora was enhanced by suitable changes in the levels of some essential
      environmental factors such as oxygen, water and nutrient contents in the soil.
      The oil content in the plot was decreased from the initial 12.50 g/kg dry soil to
      1.25 g/kg dry soil within 8 months of treatment. Simultaneously, the contents of
      copper, zinc and cadmium were decreased below the relevant permissible levels for
      soil of such type.

PMID- 15954579
TI  - First steps in microbiological calcium removal from calcium-rich industrial
      wastewater.
AB  - A novel application for the process of microbial carbonate precipitation (MCP)
      was developed. It facilitates the removal of soluble calcium from calcium-rich
      industrial wastewater. It was shown that via the urea hydrolysis pathway,
      mediated by autochthonous bacteria, calcium removal exceeding 90% could be
      maintained in a semi-continuous reactor system.

PMID- 15954580
TI  - Bacterial Ca2+ metabolism as the key to microbial carbonate precipitation.
AB  - Ca2+ -ATPase enzymes facilitate active trans-membrane transport of Ca2+ in micro
      organisms. This study investigates the hypothesis that active calcium metabolism
      under conditions of alkaline stress is a key element of microbial carbonate
      precipitation, and that the latter plays an integral part in survival of bacteria
      under alkaline conditions.

PMID- 15954581
TI  - Clinoptilolite as an ammonia binder in pig slurry.
AB  - Six gilts and six barrows are used in a 2 x 2 experiment with two phase feeding
      versus multiphase feeding and celite addition versus clinoptilolite addition.
      Nitrogen and ammonia concentration in the slurry on dry matter basis was reduced
      by 30% and 35% respectively by multiphase feeding, together with a decreased
      ratio of ammonia over nitrogen. Ammonia fixation in pig slurry by clinoptilolite
      increased from 21% after 14 days of supplementation upto 35% at 8 weeks after the
      supplementation period.

PMID- 15954582
TI  - Bacterial bioavailability and biodegradability of high-molecular weight
      hydrocarbons from oil refinery wastes.
AB  - A general problem for oil refineries is the proper disposal of production sludges
      generated during the processing of crude oil. Dumping of sludges leads to
      environmental pollution, and particularly to sediment contamination. High
      molecular weight-PAHs are important constituents of refinery wastes. These are
      toxic and recalcitrant pollutants, several of them being known mutagens or
      carcinogens. Research on biodegradability of the compounds is hampered by the
      insolubility in aqueous media. We analysed the chemical composition of a refinery
      waste sludge and determined the contents of mineral oils and PAHs. In a microbial
      investigation of the same sludge fractions we isolated several bacterial strains
      having a significant potential for breakdown of mineral oils and PAHs. Many
      techniques have already been applied to offer these compounds as substrates for
      microorganisms. Linking of the water-insoluble substrates (the PAHs, fluoranthene
      and chrysene, or the mineral oils) to Chromosorb beads and supplying them in a
      fluidised bed reactor as a single carbon source to bacterial isolates, offers a
      practical alternative in research on biodegradation. Even, this system resembles
      the common soil conditions, where bio-availability is reduced by linking of the
      contaminants to soil particles or accumulation of the products in hydrophobic
      pockets. After incubation of the carrier beads in an appropriate medium, the
      liquid fraction from the fluidised bed reactor and the carrier beads were
      collected separately and analysed for longchain hydrocarbons and for PAHs. In six
      days of incubation in an adapted broth formulation, biodegradation amounts 60.1%
      for fluoranthene and 47.2% for chrysene. Heavy hydrocarbons ranging from C10 up
      to C40 have been utilised in a thirty-day period for 72.4%. This project is a
      logical extension of our previous studies on the bio-availability of PAHs in
      contaminated sediments. We evaluate the potential use of pure cultures as a
      remedial solution to enhance the solubility and biodegradation of residual PAHs
      due to contamination by heavy fuels.

PMID- 15954583
TI  - The use of natural bio-agents for the control of cotton phytopathogens.
AB  - The use of natural antagonists as means of pre-sowing seed treatment showed high
      biological efficacy by improving seed germination, growth and productivity of
      cotton plants, and by decreasing infection by major cotton pathogens: Xanthomonas
      malvacearum, Rhizoctonia solani, Fusarium oxysporum f. sp. vasinfectum,
      Verticillium dahliae. Studies of anti-microbial properties of antagonists
      revealed significant inhibitory activity of Bacillus subtilis strains and their
      metabolites against cotton pathogens. Obtained results prove the prospective from
      the use of B. subtilis for developing complex, ecological products for biological
      control of cotton and other agricultural plants.

PMID- 15954584
TI  - Evaluation of the intrinsic mtbe biodegradation potential in MTBE-contaminated
      soils.
AB  - MTBE has only recently being used as an octane enhancer in gasoline in Europe and
      is considered as a more recent groundwater contaminant on this continent. In this
      study we examined if during the recent contamination history, European MTBE
      contaminated aquifers had developed MTBE degrading microbial communities.
      Different MTBE contaminated and non-contaminated aquifers and soils were tested
      for their intrinsic biodegradation potential. The role of the oxygen
      concentration, the availability of nutrients and the influence of the presence of
      a co-contaminant like benzene on the MTBE biodegradation capabilities of the
      indigenous microorganisms were examined. All studied soil samples showed
      degradation of benzene under all tested conditions. On the other hand only one
      aquifer showed the capacity to degrade MTBE as demonstrated by the disappearance
      of MTBE and the production of TBA, the main degradation product of MTBE.

PMID- 15954585
TI  - Kinetics of enzymatic hydrolysis of polysaccharides.

PMID- 15954586
TI  - Microbial degradation of cellulose wastes in continuous bioreactors.
AB  - This paper reports on experiments concerning the biodegradation of cellulose
      wastes from wine-producing industries, as well as from cereal crops processing in
      agricultural farms, using cellulolytic bacterial and fungal species immobilized
      on radiopolymerized hydrogels. There are described three types of such
      bioreactors and their main features. The immobilization procedures have been
      achieved using the following species of microorganisms: Bacillus subtilis and B.
      licheniformis, from bacteria, as well as Pleurotus ostreatus and Trichoderma
      viride, from filamentous fungi. The immobilization matrices were prepared by
      radiopolymerization, using a 60Co radioactive source, designed for gamma
      irradiation. A consistent increasing of dry weight loss correlated with a
      correspondent enhancement of biodegradation rate by 10 - 20%, have revealed
      significant differences of metabolic activities between these immobilized
      bacteria and fungi on radiopolymerized hydrogels and those free cells cultures of
      the same microorganisms, which were grown on agar-agar gels and used as control
      references, in all performed experiments. Regarding the enzymatic activity of
      immobilized microorganisms the registered results have revealed an increasing of
      total reducing sugars with 20 - 30 mg g(-1). The enhancement of cellulolytic
      activity was higher with 0.1 - 0.3 U min(-1), in comparison with those values
      determined for the same process performed by the same microorganisms, used as
      control.

PMID- 15954587
TI  - Monitoring of denitrification performance with combined nitrate and titrimetric
      measurements.
AB  - A sensor based on on-line measurement of nitrate and acid/base titration is
      proposed for anoxic activated sludge monitoring. The data probed from the
      preliminary experiments with denitrifying activated sludge samples using anoxic
      titrimetric sensor are information-rich with high data frequency that can be used
      further in model-based data interpretation and parameter estimation of
      denitrification process. Moreover, the sensor was able to detect intermediate
      accumulation, which is an often-observed phenomenon during the denitrification
      process. It therefore offers the possibility for use in overall performance
      evaluation of biological nutrient removal plants.

PMID- 15954588
TI  - Individual wastewater treatment in Flanders (Belgium).
AB  - In Flanders, it is not possible to centralise the infrastructure for handling all
      wastewater. Decentralised treatment should be considered an essential part of an
      overall regional policy. Decentralised wastewater treatment can be small-scale
      (20 to 2,200 Inhabitant Equivalent (IE)) or individual (less than 20 IE). This
      paper deals with the operation, performances, technological aspects and costs of
      Individual Wastewater Treatment Plants (IWTPs) in Flanders. Different treatment
      systems are described and tentatively evaluated. The total costs (capital and
      operation) can be of the same order of those of centralised systems, i.e. 100
      EURO/IE.year. In terms of overall performance, most of the systems tested in
      Flanders, i.e. aerobic biological filter, activated sludge system, submerged
      aerated filter, biorotor and percolation reed bed, appear capable to perform well
      in principle. However, there remain problems to be solved. The effluent quality
      differs 'in situ' considerably, depending on the care and attention given by the
      owner. Hence, the legislator should not only focus on certification of
      installations as such, but foremost give attention to regular validation of the
      performance at the household. In this respect, there is an urgent need for the
      design and the logistic management of proper performance control systems.

PMID- 15954589
TI  - Biocatalysis for fine chemicals.

PMID- 15954590
TI  - Metabolic engineering to produce fine chemicals in Escherichia coli.

PMID- 15954591
TI  - Determination of metabolic fluxes during glucose catabolism in Propionibacterium
      freudenreichii subsp. shermanii.
AB  - In vivo 13C Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate
      the pathways of glucose metabolism, non-invasively, in living cell suspensions of
      Propionibacterium freudenreichii subsp. shermanii. This species is the main
      ripening flora of the Swiss-type cheeses and is widely used as propionic acid and
      vitamin B12 industrial producer. The flow of labelled [1-13C]glucose was
      monitored in living cell suspensions and enrichment was detected in main products
      like [1-13C]glycogen, [6-13C]lycogen, [1-13C]trehalose, [6-13C]trehalose, [1
      13C]propionate, [2-13C]propionate, [3-13C]propionate, [1-13C]acetate, [2
      13C]acetate, [1-13C]succinate, [2-13C]succinate and [1-13C]CO2. alpha and beta
      glucose consumption could be examined separately and were catabolized at the same
      rate. Three intermediates were also found out, namely [1-13C]glucose-6-phosphate,
      [6-13C]glucose-6-phosphate and [1-13C]glucose-1-phosphate. From the formation of
      intermediates such as [6-3C]glucose-6-phosphate and products like [6-13C]glycogen
      from [1-13C]glucose we concluded the bidirectionality of reactions in the first
      part of glycolysis and the isomerization at the triose-phosphate level.
      Comparison of spectra obtained after addition of [1-13C]glucose or [U-12C]glucose
      revealed production of [1-13C]CO2 which means that pentose phosphates pathway is
      active under our experimental conditions. From the isotopic pattern of trehalose,
      it could be postulated that trehalose biosynthesis occurred either by direct
      condensation of two glucose molecules or by gluconeogenesis. A chemically defined
      medium was elaborated for the study and trehalose was the main osmolyte found in
      the intracellular fraction of P. shermanii grown in this medium.

PMID- 15954592
TI  - Racemic resolution of RS-baclofen using lipase from Candida cylindracea.
AB  - Baclofen is chemically (RS)-beta-(aminomethyl)-4-chlorobenzene propanoic acid. It
      is used in therapy of pain and as a muscle relaxant. Baclofen produces analgesia
      by increasing the concentration of gamma amino butyric acid (GABA), the major
      rapid inhibitory transmitter. Both the isomers of baclofen have different
      therapeutic activity with respect to their interaction to the receptors at the
      site of action. Lipase from Candida cylindracea has been used as a catalyst for
      resolving racemic mixtures of numerous drug molecules. The present investigation
      deals with the racemic resolution of RS-baclofen using lipase from Candida
      cylindracea and a study of the factors affecting resolution.

PMID- 15954593
TI  - A study of extracellular inulinase activity in strains of genus Kluyveromyces.
AB  - Fructo-oligosaccharide represent one of the major classes of bifidogenic
      oligosaccharides in term of their production volume, because of their favorable
      functional properties. These include: a/ improving the intestinal microflora; b/
      relieving the constipation; c/ decreasing the total cholesterol and lipid in
      serum; d/ the promotion of animal growth and e/ as low calorie non-cariogenic
      sweeteners (Chen and Liu, 1996). FOS are manufactured by two differing processes
      which result in slightly different end products--using either microbial fructosyl
      transferase (EC 2.4.1.9) or beta-fructofuranosidase (EC 3.2.1.26) with high
      transfructosylation activity. The present study reports on the biosynthesis of an
      extracellular inulinase by yeasts from genus Kluyveromyces. The strains were
      isolated from different dairy products. Some of the studied strains produced
      large amounts of extracellular inulinase activity when grown on inulin ar sucrose
      as carbon source. In addition, the effect of C/N ratio on the production of
      extracellular inulinase was studied. Thin layer chromatography showed that
      inulinase from K. species 19 was capable of hydrolyzing inulin, releasing
      monosaccharides and oligosaccharides.

PMID- 15954594
TI  - Electricity production during anaerobic waste treatment in microbial fuel cells.

PMID- 15954595
TI  - Crossflow filtration for CHO cell separation by microfiltration using crossflow
      systems.
AB  - Chinese Hamster Ovary (CHO) cells are used for fermentation of high value
      proteins in the pharmaceutical- and biotechnology industry. During the
      fermentation process the cells are grown under specific conditions in a defined
      media. The CHO cells produce extra cellular proteins. Separation and purification
      of these proteins result in the final product of high value. The production steps
      utilized in any bio-pharmaceutical process must deliver the target protein with
      high purity and yield. The first step in the production process is the separation
      of cells from the rest of the fermentation broth. Currently, stacked depth
      filters are used in this separation. The disadvantages with this method are:- 1)
      low product yield (high hold-up/wetting volume) and 2) the messy "clean-up" that
      is inherent with stacked filters. One of the main process requirements is that
      the CHO cell removal be accomplished with low cell mortality. This eases the
      subsequent process steps to purify the target protein with high yields free of
      DNA and other intracellular proteins. Additionally, the CHO cells can be reused.

PMID- 15954596
TI  - Directed evolution and Phenomics screening of new biocatalysts.
AB  - Biodiversity screening and directed evolution are two fruitful complementary
      approaches for the discovery and design of novel biocatalysts. A new technology
      for directed evolution, L-Shuffling, has been designed and patented by Proteus. L
      Shuffling technology offers several competitive advantages over other
      technologies including (i) directed evolution of large genes: L-Shuffling" means
      "Large-Shuffling"; (ii) high fidelity recombination and (iii) Control over
      location and frequency of recombination. The thousands of new recombinants
      generated by L-Shuffling can be further screened for their biochemical
      characteristics using Phenomics. Phenomics is a proprietary functional HTS
      technology designed and patented by Proteus for the screening of natural
      biodiversity as well as biodiversity generated by combinatorial biology.
      Phenomics is a function to gene structure approach which provides an alternative
      to genomics and proteomics. The traditional limits of expression libraries are
      thereby circumvented especially those related to cytotoxic products in usual or
      specific surrogate hosts. The quality of the answer given by the screening is
      directed dependent on the quality of the question asked. Thanks to a new
      substrates synthesis technology named CLIPS-O, the company can design highly
      specific molecules simulating the chemical structure and energetic state of the
      industrial substrates. The whole process of novel biocatalysts discovery has been
      automated using commercially available high throughput robotics.

PMID- 15954597
TI  - A new xylanase from Penicillium griseofulvum.
AB  - A new xylanase (pgxynA) from Penicillium griseofulvum A160 has been isolated and
      characterised using a screening method based on the ability to digest a complex
      substrate. The enzyme belongs to the hydrolase family 11 or G and shows an
      optimum pH of 5.0 and an optimum temperature of 50 degrees C. The xylanase breaks
      down the xylan to very small oligosaccharides. The corresponding gene (PGXYNA)
      was cloned and expressed in Aspergillus oryzae. A second xylanase gene with 66%
      identity to PGXYNA has also been isolated from P. griseofulvum A160. The
      recombinant pgxynA xylanase has been tested in some industrial applications. In
      bread making, hard rolls volume increased significantly using this enzyme. In
      wheat flour processing, the enzyme improved the separation of gluten from starch.
      In poultry, the addition of the A160 xylanase to a wheat-based diet led to an
      higher body weight as well as to a better feed conversion ratio.

PMID- 15954598
TI  - Recombinant lipoxygenases as biocatalysts for natural flavour production.
AB  - We identified a lipoxygenase expressed early during almond seed development.
      Biochemical and molecular characterisation showed that the enzyme produces almost
      exclusively 9-hydroperoxides which have been demonstrated to be important factors
      for the production of characteristic aromas in several fruits. An almond LOX cDNA
      was identified by RT-PCR using RNA extracted from immature almond seeds. Sequence
      analysis revealed that the identified gene is closely related to tomato fruit and
      potato tuber lipoxygenases. The isolated cDNA was cloned into pET24a and the
      expression of recombinant protein was induced in E. coli. The presence of an
      active LOX was confirmed in cells containing the recombinant vector. HPLC
      analysis of the reaction products of recombinant almond LOX confirmed that the
      isolated cDNA encodes a 9-LOX.

PMID- 15954599
TI  - Substrate specyfity of peptidases synthesised by Enterococcus facieum.
AB  - The strain Enterococcus faecium successfully used in youghurt production was the
      subject of studies. It results from the comparison of the activities of
      peptidases synthesised by E. faecium that aminopeptidases dominated Their average
      activity was about 2.5-fold higher than the average activity of dipeptidases. The
      presence of carboxy- and tripeptidases is also important from the technological
      point of view.

PMID- 15954600
TI  - Enzyme application development.
AB  - The range of enzyme applications has grown considerably in the last 10 years and
      new techniques are required to discover and evaluate the future areas of use. A
      number of different aspects of enzyme application are evaluated and consideration
      given as to how we may develop these new areas.

PMID- 15954601
TI  - Tremellan: a yeast polysaccharide with novel application potential.

PMID- 15954602
TI  - Beta-galactosidase formation in Aspergillus nidulans.

PMID- 15954603
TI  - Microbial aerobic conversion of grass cell wall polysaccharides: screening and
      strain characterization.
AB  - A screening for microorganisms able to metabolize insoluble plant cell wall
      constituents was performed. As plant material, grass (Poaceae) was chosen. The
      selectivity of the screening medium was increased by previously extracting
      soluble sugars and proteins with 1 M phosphate buffer, pH 7. About 45 bacterial
      and 44 fungal strains were isolated. A gravimetrical method had to be optimized
      to determine microbial growth and the grass cell wall material converted, since
      conventional methods couldn't be applied due to interference of the grass
      particles. The selected fungi are the most promising group for the degradation of
      insoluble plant cell wall polymers; up till 30% conversion within 7 days was
      observed with the best fungal strains.

PMID- 15954604
TI  - Sugar beet Ca-pectate gel as a cost-effective immobilized-cell matrix for metal
      biosorption.
AB  - Whole bacterial (Pseudomonas putida) and yeast (Saccharomyces cerevisiae) cells
      were immobilized by entrapment in gel beads of Ca-pectate obtained from sugar
      beet pulp and gel beads of commercial Ca-alginate (of algal origin). These
      immobilized-cell particles were tested for Cd2+ removal from dilute aqueous
      solutions and their mechanical properties were evaluated. Only Ca-pectate gel
      beads loaded with yeast cells displayed enhanced cadmium-binding efficiency (13.8
      mg Cd2+ per g dry matter) as compared to sterile beads (10.7 mg/g). Sterile Ca
      pectate gel beads were noticeably more brittle than algal alginate counterparts.
      The presence of cells reduced the mechanical resistance of both types of beads,
      however. The practical use of cell-loaded sugar beet Ca-pectate gel as a metal
      biosorbent is discussed in light of these results.

PMID- 15954605
TI  - Enzymatic extraction of carotenoids from plant material using two immiscible
      liquid phases.
AB  - The kinetics of extraction of carotenoids from orange flavedo was investigated.
      Extraction was carried out using a mixture of degrading enzymes and an edible oil
      as the solvent. More than 70 microg of carotenoids per g of wet flavedo were
      extracted within the first 3-4 hours. The results obtained were interpreted by a
      simple kinetic model considering the unsteady mass transfer of carotenoids in the
      two-phase system.

PMID- 15954606
TI  - Bioreactors based on immobilized cells.
AB  - For purification of oil-containing sewage water of oil-proceeding enterprises it
      has been elaborated by authors the laboratory bioreactor on the basis of
      immobilized mycelial Mucor miehei fungus cells with periodical and constant
      supply of purified solution. The purification process is tested on model and real
      oil-containing liquid wastes. It has been established that under true bioreactor
      exploitation, 1 g of Mucor miehei immobilized cells enables to purify more than
      100 L of sewage water, containing 0.1-0.15% of lipid substances.

PMID- 15954607
TI  - Three-factor response surface optimization of the production of dextran
      dextrinase by Gluconobacter oxydans.
AB  - Response surface methodology (RSM) and a five-level three-factor central
      composite rotatable design (CCRD) were used to evaluate the effect of glycerol
      and peptone concentration and initial pH on dextran dextrinase (DDase) production
      by Gluconobacter oxydans. Optimal fermentation conditions were 20.59 g/l of
      glycerol, 6.67 g/l of mycological peptone and an initial pH of 6.14. The
      predicted DDase yield of the optimised fermentation was 0.207 U/ml, whereas an
      actual experimental yield of 0.208 +/- 0.025 U/ml was obtained.

PMID- 15954608
TI  - In vitro studies on some probiotic properties of immobilised lactic acid bacteria
      after freezing and freeze-drying.

PMID- 15954609
TI  - Enzymatic reduction of phenylproprionaldehyde.

PMID- 15954610
TI  - Functionality of endo-beta-xylanase produced by recombinant Escherichia coli and
      Saccharomyces cerevisiae strains in bread-making.

PMID- 15954611
TI  - Molecular weight characteristics of alginate produced by Azotobacter vinelandii
      in a membrane bioreactor.
AB  - A membrane bioreactor which combines a continuous fermentor and a cross-flow
      microfiltration module enabling continuous cell recycling and removal of the
      fermentation products freed of microbial cells was tested for the production of
      alginate by Azotobacter vinelandii. The molecular weight characteristics of the
      polysaccharide produced were investigated. The macromolecular characteristics of
      alginate recovered by first filtering batch fermentation broths through different
      microporous ceramic membranes with pore sizes varying from 0.45 to 1.4 microm
      seemed to be independent of the MPS. The 0.8-microm membrane pore size (MPS) was
      selected for continuous alginate production in the membrane bioreactor. A mean
      yield value of 0.21 g alginate g(-1) saccharose was obtained and an increase in
      alginate polydispersity as incubation proceeded was observed, probably due to
      enzymatic degradation of the polysaccharide.

PMID- 15954612
TI  - Thermophilic lactic acid production on hemicellulose hydrolysate.
AB  - Lactic acid has many applications. It can be utilised as road-deicing agent, in
      the food industry or--after polymerisation--as a biodegradable plastic. The use
      of lignocellulose biomass will significantly increase the competitiveness of
      lactic acid-based polymers compared to conventional petroleum based plastics. The
      Institute for Agrobiotechnology in Tulln (IFA-Tulln) developed a process to apply
      renewable resources as cheap feedstock for production of lactic acid. The
      utilisation of thermophiles combined with a suitable pretreatment method enables
      a fermentation under non sterile conditions with detoxified hemicellulosic
      hydrolysates. This paper presents growth toxicity tests and batch experiments
      with bagasse hydrolysate, which were conducted to determine the fermentability of
      thermophilic wild type strains.

PMID- 15954613
TI  - Properties of cold-adapted subtilisine-like proteinase of endemic yeast
      Leucosporidium antarcticum.
AB  - An extracellular serine proteinase from psychrophilic marine Antarctic yeast L.
      antarcticum has been purified to homogeneity and characterized. The enzyme
      specificity, which resembles both chymotrypsin and subtilisin, as well as kinetic
      (topt of 25 degrees C, activity up to -20 degrees C, pHoptBzTyrOEt of 8.0-8.5),
      and thermodynamic properties conferring cold-adaptation of the proteinase, were
      determined The comparison of N-terminal sequence of 35 amino acid residues with
      known sequences of serine proteinases indicates that the enzyme can be
      preliminarly classified as a subtilisin-like proteinase, belonging to the
      proteinase K subfamily (clan SB, family S8, subfamily C).

PMID- 15954614
TI  - Metabolic engineering of Escherichia coli: construction and characterization of a
      gltA (citrate synthase) knockout mutant.
AB  - E. coli is one of the most important host organisms for recombinant protein
      production. However, growth and recombinant protein production can be limited by
      acetate accumulation during high-cell-density fermentations. Some of the
      strategies used to overcome this problem are based on the alteration of the
      genotype of the host. This paper discusses the construction and characterization
      of an E. coli gltA- knockout mutant. The knockout of the gene was confirmed by
      the loss of citrate synthase activity in an enzyme assay. Also the growth rate of
      the mutant on Luria Broth and Luria Broth + acetate was reduced.

PMID- 15954615
TI  - Biotechnology for aerobic production of bio-organic fertilizer.

PMID- 15954616
TI  - Biosynthesis of ergosterol by yeast Candida.

PMID- 15954617
TI  - Streptomyces strains as a source of enzymes, able to hydrolyse the Clavibacter
      exopolymer, clavan.
AB  - Two soil isolates, identified as Streptomyces sp. and designated as Streptomyces
      sp. YSDL-10 and Streptomyces sp. YSDL-20, were among the few microorganisms and
      able to hydrolyse and grow on clavan as sole carbon source. This biopolymer, very
      rich in L-fucose, is produced in by Clavibacter michiganensis subsp.
      michiganensis LMG 5604. The enzyme activity tentatively called clavanase was
      mainly detected in the culture liquid. However, qualitative tests showed that
      this activity was very weak in the supernatant. In order to test whether this
      activity was dependent of induction, several homo- and heteropolysaccharides as
      well as clavan were used as sole carbon source: the strains were grown on 10 g/l
      clavan, starch, cellulose, pectin, polygalacturonic acid, xylan or starch. After
      5 days of growth, samples were centrifuged (10.000 rpm, 20 min) and the
      supernatants were lyophilised This lyophilised preparation was used as crude
      enzyme source. This preparation was dissolved in 500 microl phosphate buffer (pH
      7.0) and added to 500 microl of clavan (0.5% w/v). Upon incubation of this
      mixture at 30 degrees C during 30 minutes, reducing sugars and L-fucose levels
      were quantified. The clavanase activity was relatively high in terms of reducing
      sugar content, but was weak in terms of L-fucose liberated. Nevertheless,
      qualitative tests performed on solid screening clavan medium showed large
      clearing zones around Streptomyces colonies. This indicates that clavan is split
      into oligosaccharides with sugar reducing moieties. The glycosidase activities
      detected in Czapek Dox-clavan medium were also weak, except for beta-D
      xylosidase. This suggests that this enzyme activity could have some role in the
      clavanase enzyme complex.

PMID- 15954618
TI  - Modulation of the gut microflora of monogastrics by feed additives.

PMID- 15954619
TI  - PCR-TGGE: a method for fingerprinting the microbial flora in the small intestine
      of pigs.
AB  - The bacterial flora of the small intestine is still not fully understood. This is
      also due to the fact that a lot of these gut inhabitants aren't cultivable. PCR
      TGGE (Temperature Gradient Gel Electrophoresis) is a molecular tool by which the
      16S ribosomal DNA of a bacterial community can be studied for its diversity.
      Based on sequence differences in the variable region V6-V8, 16S ribosomal DNA
      fragments are separated during a TGGE run. This study shows that PCR-TGGE is a
      valuable tool as it gives additional information about the flora composition that
      could not be found with classical bacteriological techniques.

PMID- 15954620
TI  - Analysis of fatty acid isomers in ruminant tissues by silver thin layer
      chromatography followed by gas chromatography.
AB  - A method for the analysis of trans fatty acids is described in this paper.
      Separation of trans isomers from the corresponding cis was based on the different
      facility with which the double bonds in the alkyl chains of both types of fatty
      acids form polar complexes with silver, and it was carried out by Thin Layer
      Chromatography (TLC), using silver nitrate impregnated plates. Further
      separation, identification and quantification of the individual C18:1 isomers,
      analysed as methyl esters, was carried out by Gas Chromatography (GC). The
      determination of the content of the isomer t11-C18:1 in ruminant tissues can
      contribute to try to elucidate the metabolic pathway formation of conjugated
      linoleic acid (CLA), shown as a fatty acid of beneficial health effects.
      Furthermore, the analysis of trans fatty acids in other dietary foods seems to be
      interesting due to their influence on the modification of the serum lipids
      profile and the role of this type of compounds in human health.

PMID- 15954621
TI  - Prevalence of Salmonella, Campylobacter and VTEC on pig farms.
AB  - Four different pig farms were sampled for the prevalence of Salmonella,
      Campylobacter and verotoxigenic E. coli (VTEC). Pigs of different age groups and
      pigs of the same age were tested by taking rectal swabs. The farm environment was
      tested by examining overshoes, and the feed and drinking water in the pens. From
      a total of 215 rectal samples of individual pigs, 15 rectal samples taken from
      animals at the same farm were positive for Salmonella. The Salmonella status of
      the pigs at this farm differed from one age group to another. S. Typhimurium was
      isolated from all the positive rectal samples and S. Typhimurium and S.
      Schwarzengrund were isolated from the environment. On two other farms Salmonella
      was only present in the environment with S. London and S. Typhimurium as
      serotypes. The presence of Campylobacter was tested in 150 rectal swabs, 51 of
      these, spread over the four farms, turned out to be positive. At all four pig
      farms Campylobacter was isolated from the environment as well. All the strains
      were identified as Campylobacter coli by a species-specific PCR. To determine if
      pigs are a reservoir of VTEC a total of 289 samples were screened for the
      presence of VTEC and 54 strains were isolated that each carried one virulence
      gene. Thirty-one strains carried the vt2e variant of the vt2 gene wich causes the
      endema disease in young pigs, four strains harboured the hlyA gene and 19 the
      eaeA gene.

PMID- 15954622
TI  - Do conventionally and biologically cultivated soils differ in bacterial diversity
      and community structure?
AB  - The effects of a long-term herbicide treatment on the microbial community of an
      agricultural soil were investigated. Therefor, molecular techniques were used to
      evaluate the structure and diversity of the soil microbial community. Eubacterial
      and group-specific primers for methanotrophs type I and II were used to amplify
      16S rRNA gene fragments from total soil DNA. These fragments were subsequently
      separated by denaturing gradient gel electrophoresis (DGGE). The structure of the
      methanotrophic community was affected by the herbicides as the patterns obtained
      from a herbicide treated soil (conventional) clustered separately from the
      control soil (biological). It seems that group-specific PCR followed by DGGE is a
      very powerful and sensitive technique to differentiate fields, which have
      received a herbicide treatment from those who did not. The diversity of the
      methanotrophic community was quantified by calculating the Shannon-Weaver index
      of biodiversity. The type I methanotrophs showed a significant decreased
      biodiversity due to the herbicide treatment but the diversity of the
      methanotrophs type II was slightly higher in the herbicide treated soil.

PMID- 15954623
TI  - Application of PCR for agriculture needs.

PMID- 15954624
TI  - Silencing of invertedly repeated transgenes in Arabidopsis thaliana.
AB  - Locus KH15, containing two invertedly repeated beta-glucuronidase (gus) genes
      separated by a palindromic sequence showed low gus expression in both hemizygous
      and homozygous seedlings, in all plant tissues tested and throughout development
      assayed up to 70 days after sowing. Removal of one of the gus genes by Cre
      mediated recombination resulted in a 10- to 100-fold increase of gus expression,
      confirming that inverted repeats and transgene silencing are strictly correlated.
      Crosses between the locus KH15 and highly expressing gus transformants further
      revealed that invertedly repeated gus genes could induce in trans silencing of
      gus copies at allelic and nonallelic positions. Double-stranded RNA produced by
      this KH15 may be responsible for this in trans inactivation.

PMID- 15954625
TI  - Linkage map construction in the outcrossing species Lolium perenne.
AB  - Genetic maps have proven useful tools in several fields of application. First of
      all, they allow to get insight into the genome organization of a species, and to
      compare the genome structures of different species. Genetic maps are also useful
      for the identification of genomic regions involved in physiological processes,
      and are valuable tools for the positional cloning of genes. In the framework of a
      project with the aim of identifying genomic regions involved in disease
      resistance in Lolium spp., we constructed genetic maps using different marker
      systems. In the ryegrass species L. perenne and L. multiflorum self-pollination
      is prevented by a very efficient self incompatibility system. This has clear
      implications in mapping studies: inbred lines and double haploids are difficult
      to produce, and if produced low seed yields are obtained. For this reason, we
      created several mapping populations by crossing two highly heterozygous unrelated
      plants. This implies that at any given locus, up to four different alleles might
      be segregating in the offspring. Different marker systems were used for the
      construction of the genetic maps. In first instance, AFLP was used as a high
      throughput marker system. This allowed to generate a high number of DNA-markers
      useful for map construction in a quick way. The drawback of the AFLP technique is
      twofold: AFLP markers are 'anonymous', and are dominant (not all alleles at a
      locus can be detected). Co-dominant marker systems, which allow to detect all
      alleles present at any locus, are much more informative and are required for the
      construction of detailed linkage maps in outcrossers. In this study, we used
      three co-dominant marker systems: SSR, STS and RFLP. The RFLP markers were
      generated using heterologous probes derived from other monocots, what should
      allow to analyze the syntenic relationships between ryegrass and other monocots.
      Using these markers generated with different techniques, a genetic map of
      ryegrass has been constructed suitable for QTL analysis and comparative genetics.

PMID- 15954626
TI  - The drl1 gene, a signal identified by transposon tagging is important for leaf
      growth.
AB  - Control of leaf shape and size was studied at the molecular level by a mutational
      approach in Arabidopsis thaliana. Mutations that affected leaf growth allowed the
      identification of genes that are important in that morphological process. The
      Activator/Dissociation (Ac/Ds) transposable element system of maize was modified
      to be used as mutagen of the Arabidopsis genome. We isolated the drl 1-2 mutation
      that is characterized by narrow leaf blades. We describe the mutant phenotype and
      have cloned and analyzed the gene. These combined analyses will give insight into
      the molecular mechanisms that control leaf growth.

PMID- 15954627
TI  - Refining of soy bean oil: detection of DNA.

PMID- 15954628
TI  - The presence of Acetobacter sp. in ensiled forage crops and ensiled industrial
      byproducts.
AB  - The presence of acetic acid bacteria (AAB) in whole crop maize silage, whole crop
      wheat silage, pressed sugar beet pulp silage, grass silage and brewer's grains
      silage was investigated. AAB could be isolated from whole crop maize silage,
      whole crop wheat silage and pressed sugar beet pulp silage, but could not be
      detected in grass silage (> 100 silo's tested) or brewer's grains silage (5
      silo's tested). Thirty AAB isolates were characterized to genus level. All
      isolates, i.e. 20 from whole crop maize silage, 5 from whole crop wheat silage
      and 5 from pressed sugar beet pulp silage, belonged to the genus Acetobacter. Two
      isolates from maize silage were further characterized. Partial 16S rRNA analyses
      revealed that one isolate was closely related to Acetobacter aceti (98% sequence
      homology), the other to Acetobacter pomorum (98% sequence homology). These
      results combined with the substrate utilization profiles indicate that these
      isolates probably represent thus far undescribed species of Acetobacter.

PMID- 15954629
TI  - Addition of formic acid or starter cultures to liquid feed. Effect on pH,
      microflora composition, organic acid concentration and ammonia concentration.
AB  - Some of the charateristics of good quality fermented liquid feed (FLF) are low
      pH, high numbers of lactic acid bacteria, and low numbers of enterobacteria. In
      order to test strategies to avoid a proliferation of enterobacteria during the
      initial phase of FLF elaboration, two in vitro studies were carried out. Addition
      of various doses of formic acid or two different starter cultures were tested.
      Adding 0.1% formic acid or L. plantarum VTT E-78076 to the liquid feed seemed to
      be addecuate ways of inhibiting the growth of enterobacteria, without depleting
      the growth of lactic acid bacteria.

PMID- 15954630
TI  - Improvement of sorghum transformation efficiency for increasing nutritional
      quality.

PMID- 15954631
TI  - Gene flow from a large scale release of genetically modified herbicide tolerant
      and hybrid winter oilseed rape (Brassica napus L.).
AB  - One of the major concerns regarding the cultivation of transgenic crops is the
      uncontrolled spread of transgenes among fields or to related wild species. To
      address this concern a long-term study has been set up to assess the amount of
      gene flow that is occurring from a large scale field trial of genetically
      modified herbicide tolerant and hybrid (GMHTH) oilseed rape. During the first
      year of the project, outcrossing of the herbicide tolerance gene from a large
      scale release of GMHTH winter oilseed rape to a non-transgenic oilseed rape crop
      in the vicinity and to wild relatives in the environment has been monitored.
      After harvesting seeds on oilseed rape plants or wild relatives, the seeds are
      sown in the greenhouse. Seedlings are sprayed with the herbicide on two different
      occasions. In this way escapes of the first treatment that are not transgenic
      will be eliminated. To confirm the transgene state of the surviving plants, leaf
      material is collected from resistant plants. DNA is extracted and the material is
      examined for the presence of the herbicide tolerance gene by means of a PCR
      assay. Results on the levels of cross pollination will be discussed.

PMID- 15954632
TI  - Characterization of carotenoid biosynthesis in Rhododendron luteum.
AB  - In the color chart of Rhododendron simsii hybrids (Belgian pot azalea), yellow is
      not yet present, although this color is wanted by growers and consumers.
      Carotenoid pigments, which are absent in azalea, are responsible for this yellow
      color of the flower petals. The first objective of this project is characterizing
      the pathway of carotenoid biosynthesis in the yellow flowers of Rhododendron
      luteum.

PMID- 15954633
TI  - Wheat transformation with glutenin gene.
AB  - The rheological properties of wheat grains are associated with the composition of
      the starchy endosperm in high molecular weight (HMW) glutenin proteins. The HMW
      glutenin 1xDy12 subunit gene was co introduced with the screenable bar and the
      reporter gus marker genes in the commercial spring wheat Minaret cultivar (cv).
      The gene of interest and the marker genes were carried by two separated plasmids,
      the pBS10BH1 and the pAhC25 respectively. Seven days old calli initiated from
      immature embryos were bombarded by use of the PDS-1000/He device. A number of
      different bombardment and culture conditions were tested. These parameters were
      evaluated on the basis of GUS transient expression. Among those a 4 degrees C
      cold pre-treatment of the spikes before immature embryos were excised, the
      culture medium incorporating activated charcoal, silver nitrate and glucose
      yielded higher GUS transient expression rate. The selective agent bialaphos was
      maintained at various stages during culture from induction of somatic
      embryogenesis to rooting of regenerated plantlets. 137 bialaphos resistant plants
      were obtained among which 109 were carried to maturity. Transgenic plants were
      characterized by PCR, Southern and SDS-PAGE analysis of the glutenin content.

PMID- 15954634
TI  - Ploidy analysis of azalea flower colour sports.
AB  - Flower colour variegation is not only a phenomenon of importance to horticulture,
      the phenotype involved is also often used as a scientific model system for the
      study of complex gene regulation processes. In the course of such studies on
      azalea, we observed a correlation between flower colour patterns, flower
      morphology and somatic polyploidy. Using high-resolution flow cytometry of
      nuclear DNA, the ploidy level was determined in flowers of different azalea sport
      families. Sports exhibiting variegated flowers with broad (> 7mm), differently
      coloured, petal edges (picotee type) proved to be tetraploid in the petal edge
      while diploid in the rest of the flower tissue. Neither flower colour pattern nor
      ploidy differences are chimeral in origin, but seem to be correlated with the
      topographic location of the cells within the flower tissue, i.e. the margin of
      the petals. The possible role of gene dosage effects and cell size involved in
      the remarkable correlation between somatic polyploidy, (flavonoid) gene
      expression and the flower morphology is discussed.

PMID- 15954635
TI  - In vitro polyploidy induction in Rhododendron simsii-hybrids.
AB  - Three in vitro protocols for the induction of tetraploid Rhododendron simsii
      hybrids were evaluated. The most successful technique was a daily application of
      mitotic poison on the apical meristem of seedlings. However, this technique was
      rather labour intensive. Direct sowing on media enriched with these compounds
      required less work but was less efficient. Mitotic inhibitors, when added to
      multiplication media, induced ploidy chimeras of existing genotypes.

PMID- 15954636
TI  - Characterisation of the gastrointestinal bacterial community in pigs fed
      fermented liquid feed and dry feed: composition and fermentation capacity
      (phenotypic fingerprint).
AB  - Feeding pigs with fermented liquid feed (FLF) has been shown to reduce the number
      of enteropathogens such as Salmonella and Brachyospira hyodysenteriae as well as
      coliform bacteria in general in the gastrointestinal tract (GIT). Also the
      commensal bacterial populations have been shown to respond to the use of FLF,
      e.g. the total counts of anaerobes, including lactic acid bacteria are reduced.
      In the present work we demonstrate that the capacity to ferment a series of
      substrates (mainly low-molecular weight carbohydrates) is reduced in caecum,
      colon and faeces of pigs fed FLF compared to pigs fed dry feed. This reduction
      could be due to the fact that these substrates are partially depleted by
      fermentation in the liquid feed prior to entering the animal. Therefore nutrient
      availability may be limited in the large intestine of pigs fed FLF, which may
      again affect bacterial enzyme synthesis and growth and thus the possibility for
      pathogenic and zoonotic bacteria to establish.

PMID- 15954637
TI  - The aerobic stability of silages influenced by metabolites of lactic acid
      bacteria.
AB  - The stability of silages after opening the silo depends strongly on the products
      formed by the microorganism flora present during the conservation process. A
      silage additive developed at IFA-Tulln showed best results on different crops. In
      the starting phase of silage fermentation, acetic acid was formed by the
      heterofermentative lactic acid bacteria L. brevis from sugars. In the later
      stages, L. buchneri converts also lactic acid into acetic acid. Several trials
      involving different formulations of starters with varying amounts of single homo-
      and heterofermentative lactic acid bacteria were tested in laboratory and clump
      silos. Finally, an optimum composition of lactic acid bacteria, which reliably
      increases aerobic stability of silages and still guaranties highest quality, was
      evaluated.

PMID- 15954638
TI  - Molecular characterisation of Arabidopsis lines tagged with a promoterless gus
      gene.
AB  - Promoter trapping has been performed through integration of a T-DNA containing a
      promoterless beta-glucuronidase (gus) reporter gene into the genome of
      Arabidopsis thaliana. A collection of T-DNA-tagged Arabidopsis lines has been
      produced with the vector pdeltagusBin19. Part of this collection was screened for
      lines with specific gus expression patterns. Here we report on the identification
      of two lines with gus expression in anthers and seeds. Both lines harbour complex
      T-DNA inserts. In one line, the integration of the T-DNA causes a male sterility
      phenotype and gus expression is developmentally regulated in anthers and flower
      bases. In the other line expression of gus is seen in the anther and seed
      endosperm.

PMID- 15954639
TI  - Effect of a bacterial xylanase and/or antibiotic growth promoter on zootechnical
      performances of piglets fed arabinoxylan rich diets.
AB  - 272 cross bred piglets (Saw (wbp x pbz) x Boar (Hamp x Pietr) were fed a basal
      diet rich in arabinoxylans from 29 days old to 84 days old. In the prestarter
      period (29 to 42 d) the basal diet was formulated with 27% wheat, 10% barley, 10%
      maize, 18% soybean meal and 22% milk products and the analytical content was
      adjusted at 13.81 MJ/kg metabolisable energy, 19.6% crude protein, 12.4% lactose,
      1.38% lysine and 0.88% SAA. During the starter period (43 to 84 d) the basal diet
      was formulated with 53% wheat, 25% barley and 16% soybean meal and the analytical
      content was adjusted at 12.91 MJ/kg metabolisable energy, 16.7% crude protein,
      1.09% lysine, 0.62% SAA.

PMID- 15954640
TI  - Use of cloned DNA fragments as reference materials for event specific
      quantification of genetically modified organisms (GMOs).
AB  - For the quantification of genetically modified organisms (GMOs) in foods and
      feeds, real-time PCR is currently the most widely applied technique. To obtain a
      % of GMO, a GMO-specific target sequence is quantified relatively to a species
      specific sequence. The correctness and reliability of the obtained quantitative
      results fully depend on the reference materials used as standards for setting up
      external calibration curves. We introduced a completely new type of standards for
      quantification of GMOs, based on cloned plasmid DNA solutions with well-known
      amounts of the sequences of interest, expressed as copy numbers. Moreover, the
      junction sequence between inserted DNA and plant DNA was used as 'unique
      identifier'. In this study, the model was applied for Roundup Ready soybean.

PMID- 15954641
TI  - Fish quality assessment with ion mobility based gas detector.
AB  - Measurement of the mixture of extractable volatile compounds of the gills of
      vendace was used in the fish freshness evaluation (Coregonus albula L.). MGD-1
      gas detector was used for the detection of volatile compound profiles of hexane
      extracts of gills. The measuring principle of MGD-1 is ion mobility distribution
      and is based on IMCELL technique. A 2.5 microl sample of hexane extract was
      heated on a ceramic plate and the vapour was carried with a constant flow (2.5
      I/min) of active carbon filtered air to the detector. The ion mobility
      distribution spectrum was measured every 1 second for 2 minutes. For reference,
      the microbial counts of gills, ATP-breakdown products (K-value) of fish flesh,
      electrical properties (Torrymeter scores) of fish skin and sensory evaluation
      scores were measured. The ion mobility distribution profiles of gills changed
      significantly during the 7 days storage period The findings related to freshness
      evaluation were supported by the reference methods. There is, however, a seasonal
      difference in the freshness probably due to seasonal variation of microbial
      flora. Besides the evaluation of fish quality, ion mobility distribution based
      technique provides a new analytical tool for food quality assessment.

PMID- 15954643
TI  - A combination of high oxygen atmosphere and equilibrium modified atmosphere
      packaging to improve the keeping quality of red fruits.
AB  - When high-barrier material is used to package fresh whole fruit in high oxygen
      atmospheres, shelf life is limited due to the accumulation of its produced CO2
      and its creation of an anaerobic atmosphere. In this study, the effect of the
      combination of High Oxygen Atmosphere and Equilibrium Modified Atmosphere
      Packaging was tested on the shelf life of two non-climacteric red fruits,
      particularly strawberries and raspberries, at 7 degrees C. Herefor, the following
      packaging systems are compared: the conventional method of packaging in a
      macroperforated high-barrier film (air conditions) (1), Equilibrium Modified
      Atmosphere (EMA, i.e. 3-5% O2 and 5-10% CO2-balance N2) (2) and two novel
      modified atmospheres: High Oxygen Atmosphere (HOA, i.e. > 70% O2-balance N2) in a
      high-barrier film (3) and HOA in a EMA film with an adjusted film permeability
      (4). The shelf life of the fruits was determined by evaluating the evolution of
      the internal oxygen, carbon dioxide and ethylene concentrations in the packages,
      the microbial and sensorial quality during the storage, the loss of weight due to
      transpiration and respiration of the fruit and the loss of marketable fruit due
      to visual decay or to Botrytis growth. The High Oxygen Atmosphere in the EMA film
      re-established after five days to an equilibrium of 3% O2 and 5% CO2. The High
      Oxygen Atmosphere in the high-barrier film remained high during the first five
      days of storage, but decreased then rapidly to anaerobic conditions, resulting in
      off-flavours and odours. To avoid an accumulation of ethylene inside the high
      barrier package, an ethylene adsorbing monolayer was added. Shelf life of
      strawberries and raspberries, packed in air conditions, was limited by growth of
      moulds and yeasts, rather than by sensorial unacceptance. On the other hand,
      sensorial properties limited the shelf life of the fruits packed under modified
      atmosphere. Especially High Oxygen Atmosphere improved the microbial quality, due
      to the inhibiting effect on yeasts and moulds. However, when oxygen was depleted
      and carbon dioxide had accumulated, sensorial quality (odour, taste andfirmness)
      was deteriorated. As this is not the case with high O2 in an EMA film, the latter
      can be assumed as a promising configuration for respiring fresh produce,
      combining the beneficial effect of high O2 and EMAP.

PMID- 15954642
TI  - The impedimetric technique for quality and hygiene control in the brewery.

PMID- 15954644
TI  - Current trends in predictive modelling of microbial lag phenomena.
AB  - This paper summarises recent trends in predictive modelling of microbial lag
      phenomena. The lag phase is approached from both a qualitative and quantitative
      point of view. Major modelling approaches and experimental results are critically
      assessed. This review mainly focuses on the influence of temperature and culture
      history on the lag phase during growth of bacteria.

PMID- 15954645
TI  - Effect of high pressure on some properties of lactic acid bacteria present in
      kefir.
AB  - The aim of the work was to determine the effect of pressurization under 700 and
      1000 MPa on the following: biochemical and antibacterial activity of individual
      strains of streptococci and lactobacilli, isolated from kefir inoculum, and of
      kefir microflora. After pressurization under 1000 MPa, the studied microorganisms
      lost their ability to inhibit the growth of the test strains, preserving the
      aroma-producing ability at the same time. The pressure of 1000 MPa caused also
      the changes in conformation of lactic acid, produced by the bacteria in skim milk
      culture. The changes in metabolism of the isolated bacteria, as being the result
      of pressurization under 700 MPa were dependent on the strain of microorganisms.

PMID- 15954646
TI  - Biosynthesis of exopolysaccharides by two strains of Lactobacillus bulgaricus in
      whey-based media.
AB  - Exopolysaccharides /EPS/ produced by lactic acid bacteria /LAB/ play a role in
      the rheology and texture of fermented milks (Cerning 1990) and could also provide
      a new source of safe additives for use in various food products. The physical
      properties of EPS, such as rheology and behaviour, depend on several factors,
      including sugar composition, type of sugar linkages, the presence of organic or
      inorganic substituents, the degree of polymerization and the length of the side
      chains. On the other hand certain physiological properties of lactic bacteria are
      of particular importance in the mechanism of their probiotic functioning:
      metabolism leading to accumulation of organic acids and other fermentation
      products in the media; resistance to those metabolites; competitive assimilation
      of the major nutrients of the media. The significant antimicrobial effect of
      probiotics towards pathogens and potentially pathogenic microorganisms is
      outlined in this context. This study was conducted on LAB strains with
      experimentally established preventive effect in control of chemical
      carcinogenesis induced by dimethylhydrazine, heavy metals and nitrites. The
      present study reports the biosynthesis of EPS by strains with proved anticancer
      effect Lactobacillus bulgaricus LB3 and Lactobacillus bulgaricus LBs on whey
      based media. A study on the action of different nitrogen sources (yeast extract
      and peptone) on the productivity of EPS and the rheological properties of medium
      was done. When whey-based medium was used the highest production of EPS was
      determined at 1% peptone--145 mg/g(-1). The carbohydrate substrate influenced the
      EPS composition. Not only the concentration but also the structure of the EPS is
      important for its thickening effect. The functional properties of the EPS
      produced could be modified by influencing the growth conditions. The influence of
      the different content of glucose on the fermentation process and the viscosity of
      the whey was performed.

PMID- 15954647
TI  - Spore-formers in foods and the food processing chain.

PMID- 15954648
TI  - Inhibitory effects of spices and herbs towards Shigella sonnei and S. flexneri.
AB  - The use of spices and herbs, their essential oils or their active compounds as
      means of control of pathogens constitutes an alternative to chemical additives In
      the present study the antibacterial activities of cloves, thyme, oregano,
      rosemary and basil on Shigella have been established. Although in a model system
      in agar media addition of 1% basil could contribute to the 'hurdle' principle and
      delay outgrowth of Shigella sp. this was not confirmed in real food conditions:
      the presence of 1% basil did not affect growth of Shigella in potato puree at 22
      degrees C or survival at 7 degrees C in spaghetti sauce. Thyme and essential oils
      and thymol and carvacrol showed inhibition of Shigella sp. in the agar well
      diffusion method (MIC 0.1-1.0%) and they have potential to be used as a
      desinfectant in the washing water e.g. in the process line of minimal processed
      vegetables. However, more studies combining sensoric properties with microbial
      analysis are needed to investigated the possible use of these compounds.

PMID- 15954650
TI  - A quality analysis of commercial probiotic products.

PMID- 15954649
TI  - Growth of Salmonella in egg white.
AB  - Six non-S. Enteritidis strains and eleven S. Enteritidis strains of which 8 were
      isolated from eggs, were tested on their growth behaviour in fresh eggs and in
      eggs of 2 and 3 weeks old hold at 20 degrees C. The growth of Salmonella at 20
      degrees C was measured at days 6, 13 and 23 after inoculation. Taking the average
      growth of the different S. Enteritidis and of the non-S. Enteritidis strains, we
      found that both groups grew very well in fresh eggs. S. Enteritidis strains grew
      as good in eggs of 2 weeks as in fresh eggs, non-S. Enteritidis strains grew
      less. When keeping the eggs 3 weeks before inoculation, both groups showed still
      a relatively high growth. Additional experiments were done on the growth of
      Salmonella in a minimal medium with an iron source together with the iron
      chelator conalbumin, and in a medium without iron and conalbumin, to overcome
      variations in viscosity and in egg composition. After 12 hours incubation at 37
      degrees C, both S. Enteritidis and non-S. Enteritidis strains grew better in the
      presence of iron than in the absence. S. Enteritidis egg isolates behaved more
      variable than S. Enteritidis non-egg isolates in the presence of iron. To check
      the influence of pH changes during ageing of eggs, we measured the growth of
      Salmonella in minimal media (with iron) of pH 8, 8.5, 9 and 9.5. All salmonellae
      seemed to grow well independently of the pH. Thus the fact that Salmonella grew
      best in fresh egg white and showed a decreasing growth in stored egg white, is
      probably not due to a pH effect. We also investigated if the presence of the yolk
      had an influence on the growth of Salmonella. We saw no general correlation so it
      seems that no components that could promote the growth of Salmonella diffuse from
      the yolk. We studied the influence of the egg sources on the variability in
      growth by comparing experiments done in eggs of 3 different sources. For the
      different strains we found a variable growth. But in general, the most important
      conclusion of our experiments is that all Salmonella strains do grow better in
      fresh egg white than in egg white of 2 or 3 weeks old. These results are
      contradictory with findings in literature (Humphrey et al., 1993) and must be
      checked with the European guidelines concerning the storage of eggs. Moreover, we
      found that even non-S. Enteritidis strains can grow well in egg white. These are
      not found in naturally contaminated eggs. It doesn't seem probable that S.
      Enteritidis could penetrate the egg shell easier than other serotypes so we
      suppose that horizontal transmission of Salmonella in eggs is of less importance
      than the vertical transmission.

PMID- 15954652
TI  - In situ delivery of therapeutic cytokines by genetically engineered Lactococcus
      lactis.

PMID- 15954651
TI  - Antimicrobial potential of probiotic lactic acid bacteria.
AB  - Antibacterial activity is an important characteristic of probiotics. A possible
      way to achieve this antibacterial activity is through the production of
      bacteriocins. This study shows that the commercial probiotic strains
      Lactobacillus johnsonii LA1 and Lactobacillus casei YIT 9029 produce
      bacteriocins. The nature of the antimicrobial compound could be derived from its
      behaviour: a narrow inhibitory spectrum (only active against closely related
      strains), loss of activity when treated with proteinases, and rather small
      molecular masses (around 6000 Da or less). Further, three bacteriocins produced
      by Lb. johnsonii LA1, Lb. casei YIT 9029 and Lactobacillus amylovorus DCE 471
      showed inhibitory activity against the human gastric pathogen Helicobacter
      pylori. However, a fourth bacteriocin produced by Lactobacillus acidophilus IBB
      801 was not able to inhibit H. pylori. This indicates that some bacteriocins
      produced by specific probiotic strains can fulfil a role in the inhibition of
      this common pathogen.

PMID- 15954653
TI  - Applications of probiotics.
AB  - Although not all action mechanisms of probiotics are fully understood, different
      beneficial health effects related to the consumption of probiotics are proven and
      accepted by the scientific world. These effects have to be put in the framework
      of a healthy diet, prevention and an improvement of the general well being. In
      this short overview, some health-beneficial effects of the regular ingestion of
      the probiotic strain Lactobacillus casei Shirota by both healthy persons and
      subjects with specific complaints is reported.

PMID- 15954654
TI  - On the enzymatic hydrolysis of whey proteins brought about by cardosin a from
      Cynara carduncunlus.

PMID- 15954655
TI  - Characterisation of lab in typical Salento Pecorino cheese.
AB  - Twenty-nine strains of Lactic Acid Bacteria isolated from the typical Pecorino
      cheese of the Salento area of Italy, were identified and grouped according to
      their genetic similarity. A preliminary characterisation of the strains was
      conducted by means of morphological and biochemical analysis, but molecular
      approaches were necessary for the clear identification of the species. For the
      species detection, the amplification and sequencing of the 16S rDNA gene was
      employed In addition, restriction analysis of amplified rDNA (ARDRA) and PCR and
      AFLP fingerprinting enabled inter- and intra-specific variation to be estimated
      UPGMA cluster analysis was used to divide the strains into distinct clusters
      which corresponded with the species delineation obtained by molecular
      identification. The data obtained show that the community of lactobacilli
      responsible for the fermentation and aging of Pecorino cheese is composed of a
      limited number of species. The main identified strains were Lactobacillus brevis,
      L. plantarum, L. casei, L. sakei, L. pentosus, L. farciminis and Leuconostoc
      mesenteroides.

PMID- 15954656
TI  - The sensory properties of gouda-type cheese depending on the degree of paracasein
      degradation.
AB  - The proteolysis in cheeses produced with working starter was different than in
      those produced with concentrate. Different dynamics of proteolysis (N-soluble)
      and peptolysis (N-amino acid) during ripening resulted in different sensory
      properties of gouda-type cheeses. Visible differences occurred in eye formation
      and texture. The cheeses produced from milk with added lisozyme were
      characterised by more soft, elastic texture compared with respective cheeses from
      milk with saltpetre.

PMID- 15954657
TI  - Effect of environmental factors on the droplet size of o/w emulsion stabilised by
      beta-lactoglobulin.
AB  - The effect of environmental factors (protein concentration, pH, ionic strength)
      on emulsification properties of beta-lactoglobulin (beta-Lg) was analysed. The
      protein was obtained from phospholipoprotein-free whey 25-fold concentrated by
      ultrafiltration (10 kDa cut off) after precipitation of alpha-lactalbumin (alpha
      La) with 6% trichloroacetic acid. The Sauter diameter D(vs) of oil droplets in
      the emulsion stabilised by beta-Lg was found to increase with increases in the
      protein concentration in the range of 0.5 to 2.0% and medium acidity in the pH
      range of 5.0 to 7.0. An increase in ionic strength in the range of 0 to 100 mM
      caused that the emulsification properties of the protein worsened as compared
      with control emulsion.

PMID- 15954658
TI  - Coalescence stability of alpha-lactalbumin-stabilised emulsion.
AB  - The effects of acidity (pH 5.0 to 7.0) and protein concentration (0.5 to 2.0%) on
      coalescence stability of o/w emulsion stabilised by alpha-lactalbumin (alpha-La),
      that was salted out from rennet whey with 7% NaCl at pH 2.0, were studied
      Irrespective of pH and alpha-La concentration, the Sauter diameter (D(vs)) of an
      oil droplet was found to increase on storing the emulsion for 4 h at room
      temperature and the conditions preventing from creaming and accelerating
      destabilisation of the emulsion. The effect of pH on emulsion coalescence
      stability was greater than that of protein concentration.

PMID- 15954659
TI  - Identification of whey proteins in tradional Bulgarian yougurt.
AB  - Functional foods hold a great promise for future trends in human nutrition.
      Consumption of milk and milk products have a pronounced probiotic effects
      together with the expected modification of allergenic properties of milk due to
      the process of fermentation. The proteolytic system of lactic acid bacteria
      consists a cell wall bound proteinase and several intracellular peptidases, and
      can contribute to the liberation of bioactive peptides. Food-derived bioactive
      peptides are claimed to be health enhancing components which can be used for
      functional food. In our study we focused our attention on beta-lactoglobulin and
      alpha-lactalbumin in early stages of yogurt fermentation of traditional Bulgarian
      products. Biochemical techniques were used to measure the concentration of these
      two whey proteins during fermentation. At a result of the done study alteration
      in the concentration of beta-lactoglobulin and alpha-lactalbumin were detected.
      The studied proteolytic activity of the strains, used in the fermentation process
      confirmed the received results.

PMID- 15954660
TI  - Survival rate of preserved cultures contained in baker's vaccine.
AB  - The studies comprised the preparation and preservation, by the method of spray
      drying, of baker's vaccine composed of lactic acid bacteria. The selection of
      particular strains was conducted taking into consideration the fermentation
      activity and growth dynamics of Lactobacillus rods isolated from plant material.
      Mixed vaccine was composed of chosen monocultures, characterized by the highest
      acidifying activity (4 strains). Before the vaccine was preserved, it had been
      used for making bread leaven (of rye flour) whose activity and usefulness for rye
      bread production was then determined The vaccine was subjected to spray-drying.
      The survival rate of Lactobacillus rods was determined directly after drying and
      during storage. It was found that the parameters of spray-drying applied in the
      experiment caused a considerable reduction in the number of vaccine components-
      by 2 log on average.

PMID- 15954661
TI  - Influence of temperature and acidity of milk on the degree of transfer of
      coagulating preparations from milk to the cheese grain.
AB  - The effect of temperature, milk acidity and time of curd holding on the degree of
      passage of enzymic coagulating preparations, was studied. It was found that the
      degree of the passage of the examined preparations was increasing together with
      the rise of temperature and milk acidity. Any significant effect of the curd's
      holding on the quantity of the preparation in the cheese grain was not found.

PMID- 15954662
TI  - Effect of Lactobacillus plantarum bacteriocin on gram-negative rods.
AB  - The antibacterial effect of bacteriocins synthesized by Lactobacillus plantarum
      isolated from fermented carrot juice on Enterobacteriaceae rods coming from food
      was studied in the experiment. Their antibacterial activity was determined
      employing the diffusion method, well technique. The results show that the
      bacteriocins examined were characterized by a different effect on test strains
      whose development was inhibited at the activity level from 256AU/ml to 4AU/mL.

PMID- 15954663
TI  - Use of lactic and propionic acid bacteria in the production of fermented parsley
      juice.
AB  - Taking into consideration the proliferation rate of Propionibacterium sp. cells,
      pH changes and sensory properties of the fermented product obtained, selection of
      propionic acid bacteria (PAB) was made in order to determine their usefulness for
      the production of fermented parsley juice. The analysis included 12 strains,
      belonging to the following species: P. thoenii (4 strains), P. jensenii (6
      strains), P. freudenreichii (1 strain) and P. acidipropionici (1 strain). The
      experiments show that many strains of propionic acid rods develop well in parsley
      juice, allowing to achieve the desired taste qualities of the product. The
      Propionibacterium strains selected by elimination were used as components of
      vaccine containing: Lactobacillus plantarum, Lactococcus lactis ssp. lactis,
      Saccharomyces cerevisiae.

PMID- 15954664
TI  - Evaluation of the antioxidant activity and ascorbic acid content during the room
      temperature storage of apple subjected to a combined preservation technology.

PMID- 15954665
TI  - Advances of the WITY system: yeast performance evaluation during the production
      of sweet wine using Mavrodafni and Carbarnet sauvignon.
AB  - The production of sweet wine from the Mavrodafni and Cabernet sauvignon varieties
      was explored. External inoculation with oenological yeast strains was employed.
      The performance of the two yeast strains were studied under batch and continuous
      mode and in free and immobilised states. The kinetics of the different
      carbohydrates was studied and the main oenological parameters were measured.

PMID- 15954666
TI  - Activity of adventitious Enterococcus strains on model curdled caprine milk:
      microbial growth and evolution of concentration of organic acids and lactose
      throughout time.
AB  - Enterococci offer a few unique advantages when compared with other lactic acid
      bacteria in that they are resistant to phages, stable lactose fermenters,
      tolerant to relatively high concentrations of sodium chloride and optimal growers
      at relatively high temperatures (Franz et al., 1999). Such genus occurs and grows
      in a variety of cheeses, especially artisanal cheeses produced in Southern Europe
      usually from raw milk; they are claimed to play a major role in ripening and
      aroma development in such cheeses (Freitas et al., 1995; Macedo et al., 1995).
      Enterococci can produce lactic, acetic, propionic and succinic acids (Ocando et
      al., 1994), compounds that have been correlated with flavor characteristics of
      cheese; hence strains of Enterococcus have been successfully used as starters for
      different cheese (Franz et al., 1999).

PMID- 15954667
TI  - Synergistic and antagonistic properties of selected cultures of lactic acid and
      propionic acid bacteria. Part II. Proteolytic activity.
AB  - The objective of this work was to study the dynamics of proteolytic activity for
      selected cultures of propionic acid and lactic acid bacteria used in the rennet
      cheese production. The studies were carried out in two model systems, with CH-N
      19, Nizostar and their associated cultures in two media differing in the nitrogen
      compound structure. The addition of coagulating enzyme to the medium accelerated
      the proteolytic processes occurring upon the contribution of the examined
      cultures but did not influence the changes in the aminopeptidase specificity
      towards the substrates used (Leu-pNA for LAB and Pro-pNA for PAB).

PMID- 15954668
TI  - Synergistic and antagonistic properties of selected cultures of lactic acid and
      propionic acid bacteria. Part I. Fermentation activity.
AB  - The objective of this work was to study the dynamics of fermentation activity of
      selected cultures of lactic acid and propionic acid bacteria used in the cheese
      production. At the same time, it was decided to follow their interactions. The
      studies were conducted in two model systems with CH-N-19, Nizostar, and their
      associated cultures in two media. On a basis of the evaluation of physiological
      and fermentation activities, the antagonistic properties between the examined
      culture systems were not found and the differences observed only resulted from
      specific traits of the examined microorganisms.

PMID- 15954669
TI  - Assessment of results replicability of staphylococci identification in lactic
      acid cheese under various diagnostic methods.

PMID- 15954670
TI  - Extraction and PCR analysis of soy DNA in chocolate.
AB  - The manner in which to discriminate between genetically modified (GM) versus non
      modified foodstuffs is based on the presence of newly introduced genes at the
      protein or DNA level. Current available methods are almost exclusively based on
      the polymerase chain reaction (PCR). These methods consist of three steps: DNA
      isolation, amplification of the desired DNA fragment and visualisation of the
      obtained amplification products. The first and crucial step is the DNA isolation.
      In this study three different methods are described for the isolation of DNA from
      chocolate, two of which are commercial kits. The results indicate that both kits,
      in contrast with the non-commercial method, are suitable for the isolation of DNA
      from chocolate, provided that the adapted PCR conditions are applied.

PMID- 15954671
TI  - Extractibility of the protein and peptide fraction for different types of dry
      fermented sausages in relation to GPC-analysis.
AB  - The use of GPC (gel filtration chromatography) for investigating the proteolysis
      during fermentation and ripening of dry fermented sausages (Northern and
      Mediterranean type) and the choice of a suitable extraction solvent for this
      technique was evaluated. Solvents in a wide range of acidity were used in this
      experiment (pH 0.5-13). A calculation of the percentage extracted
      nitrogencompounds for each solvent and a comparison of the GPC-profile for each
      extract select the HCl-dilutions with a pH 1 to 3 as the most suitable extraction
      solvent. Although very basic solvents extract most of the protein and peptide
      fraction, they lead to some degradation of the proteins and peptides and are not
      reliable. Clear differences between the GPC-profiles for both types of sausages
      were not observed.

PMID- 15954672
TI  - Vibrations in milk transportation.
AB  - During transport of milk in three-cell tank truck, the vibrating acceleration
      ranged generally on the level of 0.5 to 2g (0.5 to 20 m/s2) at the vibrating
      frequency 2 to 60 Hz. The vibration increased proportionally to the driving speed
      of tank truck, being dependent on the type and surface condition of road and the
      efficiency of space filling in the container, with lower vibration levels at
      lower filling.

PMID- 15954673
TI  - Influence of vibrations on fat-phase of milk.
AB  - Model studies are presented on the influence of vertical and horizontal
      vibrations of different frequency (10 to 60 Hz), constant acceleration 1 g, and
      constant exposition time 60 min on changes in the lipid fraction of milk. It was
      found that the changes in the examined characteristics of milk fat were dependent
      on and intensified with the frequency.

PMID- 15954674
TI  - Effect of high pressure on the survival rate and antibacterial activity of
      Bifidobacterium strains.
AB  - The effect of pressures of 1000, 700 and 400 MPa/15 min on the survival rate of
      Bifidobacterium infantis 1/1 was studied. 24 h milk cultures, Garsch cultures,
      and yogurt--to which centrifuged cell biomass of these bacteria was introduced-
      were subjected to pressurization. It was found that a pressure of 1000 MPa
      inactivated populations from 10(7) to 10(9) cfu/ml in all the environments
      examined. Only tens of cells in milk cultures survived a pressure of 700 MPa.
      Populations reduced by 4 or 5 log, depending on the environment, survived a
      pressure of 400 MPa. The greatest number of cells died in yogurt, where
      population reduction was 5 log. Bifidobacterium infantis 1/1 in milk cultures
      produced antibacterial metabolites active towards 89% of pathogenic bacteria
      strains: Enterobacteriaceae rods and species S. aureus, L. monocytogenes, B.
      cereus. Garsch cultures inhibited the growth of 67% of the same test strains. The
      antibacterial effect of experimental yogurt was much weaker than that of
      cultures, but it inhibited the growth of a higher number of test strains than
      control yogurt. Culture and yogurt pressurization with 700 MPa caused
      inactivation of antibacterial metabolites in all the environments.

PMID- 15954675
TI  - Effect of Propionibacterium acidipropionici on the growth of Yersinia
      enterocolitica.
AB  - The antibacterial effect of Propionibacterium acidipropionici culture on a whey
      medium was determined in preparations subjected to cell inactivation with UV
      radiation and chloroform treatment; in concentrated biomass, centrifuged and
      suspended in sterile water; in a preparation subjected to cell inactivation with
      chloroform. The test strain was Yersinia enterocolitica 8. The preparations and
      culture were added, as biopreservatives, to broth media where the test strain was
      cultured, checking periodically the population development. It was found that a
      whey culture of P. acidipropionici was characterized by antibacterial activity of
      64 AU/ml, but after cell inactivation this activity decreased to 16 and 8 AU/ml,
      depending on the method employed. The activity of concentrated biomass of live
      cells was at a level of 128 AU/ml, and after inactivation with chloroform--8
      AU/ml. An addition of biopreservatives to the growth medium caused inhibition of
      test strain proliferation. Its degree depended on the antibacterial activity of
      the environment and population size. In the environment with activity of 42.7
      AU/ml the strain Y. enterocolitica 8 whose population was hundreds of cells per
      ml died after 8 hours of incubation. A larger population, i.e. 10(5) cfu/ml,
      survived under these conditions, but did not proliferate during 24 hours of
      culturing.

PMID- 15954676
TI  - Science on the fringe: ESP, UFOs and reincarnation are treated with respect at
      the world's most bizarre scientific conference.

PMID- 15954677
TI  - Inside the Korean cloning lab.

PMID- 15954678
TI  - Stress related factors among primary and part-time caregiving grandmothers of
      Kenyan grandchildren.
AB  - The present study examined whether the total stress experienced by 241 caregiving
      grandmothers was linked to levels of care provided, child behavioral difficulty,
      and perceived availability of emotional and instrumental support. One hundred and
      twenty eight of these participants adopted their orphaned grandchildren on full
      time basis. The rest (n = 113) were grandmothers providing partial parenting
      roles in households that also included one of these children's biological
      parents. The results indicated that the full-time grandmothers experienced
      significantly higher levels of stress than did the part-time caregivers. The
      total stress experienced was related to these participants' perception of child
      behavioral difficulty and limited instrumental support.

PMID- 15954679
TI  - Depression and caregiver mastery in grandfathers caring for their grandchildren.
AB  - Kin caregiving research tends to focus on the experiences of grandmothers. Often
      unnoticed and underserved are grandfathers who also take on this responsibility.
      Here, two groups of grandfathers participated in focus group interviews to
      discuss their experiences as caregivers to their grandchildren. Common themes for
      the grandfathers were the feeling of missing freedom, experiencing child rearing
      differently now than they had with their own children, and fear of what would
      happen to the children should their health fail. Thirty-three grandfathers also
      answered questions about themselves; their grandchild; need, use, and
      satisfaction with formal services; depression; and caregiving mastery. A sample
      of 33 grandmothers selected from a previous study was matched to the grandfathers
      on age, race, and marital status. Differences in depressive symptoms between the
      grandfathers and grandmothers were statistically significant. There was no
      statistically significant difference between the grandparent caregivers on
      caregiving mastery. These findings suggest that there may be differences in the
      impact of caregiving for grandmothers and grandfathers. These differences should
      be further investigated.

PMID- 15954680
TI  - The responsibility continuum: never primary, coresident and caregiver-
      heterogeneity in the African-American grandmother experience.
AB  - This article examines diversity among 542 African-American grandmothers from the
      Woodlawn Longitudinal Study. Women were categorized on the basis of their
      household composition, degree of care provided to grandchildren, and status of
      primary caregiver to grandchildren during lifetime. Overall, 67.7% of the sample
      engaged in parenting and exchange behaviors at high or moderate levels. Twenty
      seven percent of the sample coresided with and provided care to grandchildren,
      28% did not coreside but had been primary caregivers in the past, and 45% did not
      coreside and had never been primarily responsible for a grandchild. Heterogeneity
      was found among seven grandmother types on economic measures, life events, and
      grandchild characteristics. Grandmothers with earlier primary responsibility and
      those currently in homes of three or more generations were associated with poor
      outcomes. Policy and practice can be informed by additional research on status,
      context, and timing of assumption of responsibilities for grandchildren.

PMID- 15954681
TI  - Latina grandmothers raising grandchildren: acculturation and psychological well
      being.
AB  - Grandparent involvement in raising grandchildren has become increasingly
      prevalent and represents the family's strength for managing crises and
      transitions. This study examined acculturation, socioeconomic resources, and
      family factors related to well-being among 357 Latina caregiving grandmothers.
      Positive affect was related to greater language acculturation and factors
      suggesting participation in mainstream society-income and health. In contrast,
      higher life satisfaction and lower negative affect were more evident among the
      less acculturated. These relationships disappeared with controls, explained by
      greater social resources among less acculturated grandmothers: more were married
      and had the parent at home; fewer assumed care because of the parent's substance
      related problems. The parent's presence in the household was related to a higher
      level of grandmother's well-being until more sensitive family factors were
      considered. Furthermore, raising grandchildren with behavior problems was related
      to the grandmother's negative affect. Results suggest that professions should
      target economic needs of new immigrants, as well as assisting with troubled
      grandchildren and dysfunctional parents.

PMID- 15954682
TI  - Grandmothers' diaries: a glimpse at daily lives.
AB  - Little information exists about the daily lives of women who are grandmothers,
      and the differences in daily stresses based on caregiving status to
      grandchildren. This content analysis examines the stresses of 64 grandmothers as
      grouped by caregiver status (grandmothers raising grandchildren, grandmothers
      living in multigeneration homes, non-caregivers to grandchildren) as recorded in
      three-week diaries. The nature of salient issues and stressful interactions
      differed by caregiver groups. Grandmothers raising grandchildren reported more
      stresses related to grandchildren's routines, activities, and school progress,
      more time pressure, and difficult interactions with grandchildren. The diary
      entries of grandmothers in multigenerational homes reflected their supplemental
      role in childcare, and sometimes stressful interactions with other family
      members. Grandmothers with no routine caregiving to grandchildren reported more
      involvement with those outside the immediate family. Many general concerns about
      the well-being of the family represent commonalities in grandmothers despite
      differences in current caregiving roles to grandchildren.

PMID- 15954683
TI  - Canadian First Nations grandparents raising grandchildren: a portrait in
      resilience.
AB  - Between 1991 and 2001, there was a 20% increase in the number of Canadian
      children under 18 years old who were living with their grandparents without a
      parent present in the home. Recent research revealed that Canadians of First
      Nations origin, including North American Indians, Metis, and Inuit, were vastly
      over-represented among grandparents raising grandchildren in skipped generation
      households (households which include only grandparents and grandchildren). Using
      custom tabulation data from the 1996 Canadian Census, this article presents a
      profile of First Nations Canadian grandparents raising grandchildren in skipped
      generation households. Despite extremely high rates of poverty and disability,
      one-third of First Nations Canadian skipped generation families were raising two
      or more grandchildren. In comparison to other grandparent caregivers, First
      Nations custodial caregivers were more likely to also be caring for a senior
      (23%) and to spend more than 30 hours a week on childcare duties (46%) and on
      housework (41%). Implications for policy, practice, and research are discussed.

PMID- 15954684
TI  - African-American grandmothers as health educators in the family.
AB  - More than 18,000 adolescents die each year in the United States from bicycle,
      motorcycle, car, and truck accidents. This study sought to understand the role of
      African-American grandmothers as prevention-oriented health educators in the
      family. Full Model Fitted Regression Analyses were conducted on a sample of
      African-American grandmothers (N = 105) with 10- to 19-year-old grandchildren.
      Findings suggest that grandmothers who adopt a proactive, teaching role with
      their grandchildren are more committed to doing so, confident about doing so, and
      in a context to do so. In particular, grandmothers who co-reside with their
      grandchildren are more likely to teach them about how to prevent transportation
      accidents than those who do not co-reside. These findings could contribute to
      innovations in existing grandparent education curricula.

PMID- 15954685
TI  - Smile on wings: a tsunami relief mission.

PMID- 15954686
TI  - Principles of external fixation of the femur.
AB  - External fixation may be indicated for a variety of traumatic and reconstructive
      conditions involving the femur. Regardless of underlying pathology and type of
      external fixator used, fixator placement requires a clear understanding of the
      unique skeletal and soft-tissue anatomy of the femur. In this review, we outline
      the principles of safe and effective placement of external fixation for the
      femur. By following these guidelines regarding femur anatomy and alignment,
      proper pin-insertion techniques, and aftercare, surgeons should be able to obtain
      satisfactory results for the majority of appropriately selected patients.

PMID- 15954687
TI  - Minimally invasive spine surgery.
AB  - This article reviews the rationale, suggested benefits, and techniques of
      minimally invasive surgery (MIS) of the spine. While the efficacy and outcomes of
      open spinal decompression and fusion procedures have been validated in numerous
      longitudinal studies, these surgeries typically involve significant soft-tissue
      dissection and muscle retraction. MIS techniques aim to minimize iatrogenic
      damage to the soft tissues around the spine while allowing surgeons to perform
      effective decompression and fusion procedures. Here we summarize the rationale
      for the trend toward spinal MIS and highlight the more common procedures.

PMID- 15954688
TI  - Remodeling of the proximal femur after varus osteotomy.
AB  - The purpose of this study was to measure the remodeling of the proximal femur
      after varus osteotomy and to determine the factors that may affect the degree of
      angular correction. In addition, we wanted to determine the degree of remodeling
      over time. One hundred nine varus proximal osteotomies were performed on 66
      children with hip dysplasia. Neck-shaft angles were measured on preoperative,
      immediate postoperative, and follow-up radiographs. Remodeling of the proximal
      femur occurred after varus osteotomy as long as the physes of the proximal femur
      continued growing. Patients' remodeling varied widely; however, gender,
      ambulatory status, and original diagnosis had little effect on the magnitude of
      remodeling. Results from this study reinforce the need to follow patients with
      periodic hip radiographs until growth is complete.

PMID- 15954689
TI  - Symptomatic unilateral os hamuli proprium.

PMID- 15954690
TI  - Ipsilateral complex dorsal dislocations of the index and long finger
      metacarpophalangeal joint.

PMID- 15954691
TI  - Internal torsion of the distal femur as a cause of habitual dislocation of the
      patella: a case report and a review of causes of patellar dislocation.

PMID- 15954692
TI  - Leiomyosarcoma of bone.

PMID- 15954693
TI  - Temporal and geographic variation in hip fracture rates for people aged 65 or
      older, New York State, 1985-1996.
AB  - We describe temporal and regional variation in hip fracture rates for people aged
      65 or older in New York state (NYS) from 1985 to 1996. Our descriptive study was
      of all hip fracture cases admitted to NYS hospitals during that period. Case data
      were obtained from the Statewide Planning and Research Cooperative System
      (SPARCS) of the NYS Department of Health. US Census Bureau population estimates
      were obtained for each year from 1985 to 1996 to compute the annual hip fracture
      rate for each NYS county. These rates were adjusted for differences in age,
      gender, and race and were compared using logistic regression. Approximately
      14,000 hip fractures occurred annually from 1985 to 1996. The annual rate (number
      of hip fractures per 1000 population) decreased from 6.4 in 1985 to 5.3 in 1996.
      White women aged 85 or older had the highest rate (26/1000); nonwhite men aged 65
      to 69 had the lowest rate (<1/1000). Statewide annual rates decreased slightly
      over time, but this change was not reflected in all age, gender, and race
      subgroups. There was important, consistent variation in county rates after
      adjustment for age, gender, and race. Other researchers have identified
      geographic variation in national rates, but the postulated environmental and
      weather-related factors (eg, water fluoridation use; rainfall and sunshine
      amounts) have explained only a small proportion of this variation. Identification
      of risk factors that can better explain regional rate variation may lead to
      development of intervention strategies that could significantly reduce the risk
      for hip fracture among people 65 or older.

PMID- 15954694
TI  - [The evolution of orthodontic thought from 1728 to 2004].

PMID- 15954695
TI  - [Tweed-Merrifield technique and vertical dimension in hyperdivergent Class II].
AB  - The cases presented in this paper share a common skeletal characteristic,
      hyperdivergence, a common therapeutic strategy, similar diagnostic elements, and
      a common choice of non-symmetrical extractions. Interceptive treatment is
      especially useful for this type of malocclusion to prevent deep over-bites,
      atypical habits, and severe malocclusion. In the Tweed-Merrifeld technique,
      orthodontists use careful dental, occlusal, cephalometric, and esthetic
      evaluations to establish an appropriate treatment plan and therapeutic strategy
      whose goal will be: to eliminate unhealthy compensations, re-position, if
      necessary, alveolar structures on basal bone, reduce anterior-posterior and
      vertical discrepancies, favor anterior mandibular rotation, improve facial
      esthetics, restore functional occlusion, and assure stability of results. Because
      of its consistent capability of achieving predictable resolution of the most
      varied and complex orthodontic disorders, the author has chosen this technique
      for routine use in his daily orthodontic practice.

PMID- 15954696
TI  - [Control of vertical dimension in the Root technique. Part 2. Class II].
AB  - Hyperdivergent, or high angle, Class II skeletal malocclusions require a
      reduction in that angle so that an optimal counter-reduction of the mandible can
      be obtained. Four of these types of cases are analyzed here to show: in the
      first, treated without extractions, the limitations of this approach: the poor
      esthetic result derives from the incomplete retraction of incisors because of the
      occlusal deficits further correction would have incurred; in the second, treated
      with extractions of upper and lower first bicuspids, that a reduction of the
      angles SNM from 45 degrees to 40 degrees, FMA from 27 degrees to 24 degrees and
      ANB from 90 to 40 was obtained; in the third case, treated with extractions of
      the upper first bicuspids and the lower second bicuspids, that a counter-rotation
      of the mandible was required in order not to aggravate the esthetic problem while
      the dental deformity was being corrected. Angle SNM was reduced from 30 degrees
      to 25 degrees, FMA from 26 degrees to 20 degrees, and ANB from 7 degrees to 2
      degrees; and, in the fourth case, where an atypical extraction scheme was
      elected, that an effective orthodonticsurgical alternative is available. Thanks
      to an anchorage conception specifically designed for this case by T. Root
      allowing for extraction of upper first molars, angle SNM was reduced from 38
      degrees to 35 degrees, FMA was changed from 28 degrees to 23 degrees, and ANB
      dropped from 10 degrees to 3.5 degrees.

PMID- 15954697
TI  - [Respiration in orthodontic practice].
AB  - In this paper, the author presents his method of dealing with breathing problems
      when he conducts an orthodontic consultation. Because they can interfere with
      growth, the author believes that ventilation disorders should be dealt with
      promptly so that they cannot cause skeletal discrepancies. After having reviewed
      the literature, the author presents his clinical procedures for uncovering and
      treating breathing disorders and then shows treated cases to illustrate his
      techniques, one of the most important of which, palate splitting, is simple,
      effective and virtually without risk. In addition to its clear orthodontic
      benefits, rapid palate expansion can prevent the growth problems that frequently
      accompany breathing disorders. He believes that the Delaire's facial mask is the
      ideal preventive device for dealing with problems associated with skeletal Class
      III malocclusions. He asserts that, when indicated, the device can work well in
      conjunction with palatal expansion.

PMID- 15954698
TI  - Evaluation of fertilization-to-planting and fertilization-to-harvest intervals
      for safe use of noncomposted bovine manure in Wisconsin vegetable production.
AB  - Fresh bovine manure was mechanically incorporated into loamy sand and silty clay
      loam Wisconsin soils in April 2004. At varying fertilization-to-planting
      intervals, radish, lettuce, and carrot seeds were planted; crops were harvested
      90, 100, 110 or 111, and 120 days after manure application. As an indicator of
      potential contamination with fecal pathogens, levels of Escherichia coli in the
      manure-fertilized soil and presence of E. coli on harvested vegetables were
      monitored. From initial levels of 4.0 to 4.2 log CFU/g, E. coli levels in both
      manure-fertilized soils decreased by 2.4 to 2.5 log CFU/g during the first 7
      weeks. However, E. coli was consistently detected from enriched soil samples
      through week 17, perhaps as a result of contamination by birds and other
      wildlife. In the higher clay silty clay loam soil, the fertilization-to-planting
      interval affected the prevalence of E. coli on lettuce but not on radishes and
      carrots. Root crop contamination was consistent across different fertilization-to
      harvest intervals in silty clay loam, including the National Organic Program
      minimum fertilization-to-harvest interval of 120 days. However, lettuce
      contamination in silty clay loam was significantly (P < 0.10) affected by
      fertilization-to-harvest interval. Increasing the fertilization-to-planting
      interval in the lower clay loamy sand soil decreased the prevalence of E. coli on
      root crops. The fertilization-to-harvest interval had no clear effect on
      vegetable contamination in loamy sand. Overall, these results do not provide
      grounds for reducing the National Organic Program minimum fertilization-to
      harvest interval from the current 120-day standard.

PMID- 15954699
TI  - Comparison of the microflora on organically and conventionally grown spring mix
      from a California processor.
AB  - Considerable speculation has occurred concerning the potential for higher numbers
      of foodborne pathogens on organically grown produce compared with produce not
      grown organically. The microflora composition of spring mix or mesclun, a mixture
      of multiple salad ingredients, grown either by organic or conventional means was
      determined. Unwashed or washed spring mix was obtained from a commercial
      California fresh-cut produce processor who does not use manure in their
      cultivation practices. Fifty-four samples of each type of product were supplied
      over a 4-month period. Analysis included enumeration of total mesophiles,
      psychrotrophs, coliforms, generic Escherichia coli, lactic acid bacteria, yeasts,
      and molds. In addition, spring mix was analyzed for the presence of Salmonella
      and Listeria monocytogenes. The mean populations of mesophilic and psychrotrophic
      bacteria, yeasts, molds, lactic acid bacteria, and coliforms on conventionally
      grown spring mix were not statistically different (P > 0.05) from respective mean
      populations on organically grown spring mix. The mean population of each
      microbial group was significantly higher on unwashed spring mix compared with the
      washed product. Of the 14 samples found to contain E. coli, eight were from
      nonwashed conventional spring mix, one was from washed conventional spring mix,
      and four were from nonwashed organic spring mix. Salmonella and L. monocytogenes
      were not detected in any of the samples analyzed.

PMID- 15954700
TI  - A study of the prevalence and enumeration of Salmonella enterica in cattle and on
      carcasses during processing.
AB  - Salmonella prevalence and counts were estimated for samples from the oral cavity,
      hide, rumen, and feces of 100 cattle at slaughter and from the pre- and postchill
      carcasses of these cattle. Samples were collected from 25 consecutively
      slaughtered cattle from each of four unrelated groups slaughtered at a single
      abattoir on different days. Ten additional fecal samples from each group were
      collected from their respective abattoir holding pens prior to slaughter. The
      prevalence of Salmonella was estimated using automated immunomagnetic separation,
      and the counts were estimated using a combination of most probable number (MPN)
      and automated immunomagnetic separation. A total of 606 samples were collected
      with Salmonella isolated from 157 (26%), including 29% of oral cavities, 68% of
      hides, 16% of feces collected after evisceration, 25% of rumen samples, 2% of
      prechill carcasses, 3% of postchill carcasses, and 48% of feces collected from
      holding pens. The prevalence and count of Salmonella varied between the different
      groups of animals tested. The highest count obtained was from a rumen sample (1.1
      x 10(4) MPN/g). Other counts were generally low, with a maximum count in feces
      collected after evisceration and in the abattoir holding pens of 93 and 23 MPN/g,
      respectively. The highest count on hides, in oral cavities, and on carcasses was
      4.8 MPN/cm2, 23 MPN/g, and 0.31 MPN/cm2, respectively. Even though Salmonella was
      present on the hides and in the rumen and feces of at least one animal from each
      group of cattle, the processing of animals at this abattoir resulted in few
      contaminated carcasses, and when contamination occurred, Salmonella was detected
      at low numbers.

PMID- 15954701
TI  - Growth history influences starvation-induced expression of uspA, grpE, and rpoS
      and subsequent cryotolerance in Escherichia coli O157:H7.
AB  - In this study, we investigated the effect of starvation on cryotolerance of
      Escherichia coli O157:H7 grown in tryptic soy broth (TSB) and Luria-Bertani broth
      (LB). Starved cells (cells suspended in water at 37 degrees C for 6 h) and
      control cells (cells in TSB or LB) were frozen at -18 degrees C for up to 240 h
      in their respective growth media. The E. coli grown in TSB showed a greater
      starvation effect (the difference in percent survival of starved and control
      cells) and cryotolerance. The starved E. coli grown in TSB showed a 30% increase
      in their ability to survive frozen storage for 24 h at -18 degrees C. The
      corresponding increase in survival for LB-grown E. coli was only 3.8%.
      Cryotolerance induced by starvation of TSB- and LB-grown E. coli was correlated
      with the expression of genes involved in general stress response pathways, such
      as uspA, grpE, and rpoS. The expression of uspA, grpE, and rpoS was quantified by
      measuring the green fluorescence generated from autofluorescent E. coli harboring
      puspA::gfp, pgrpE::gfp, and prpoS::gfp gene fusions. The results obtained in this
      study indicate that uspA, grpE, and rpoS were induced on starvation when E. coli
      was grown in TSB, and their expression correlated well with subsequent induction
      of cryotolerance developed at -18 degrees C. In contrast, cells grown in LB and
      subsequently exposed to starvation conditions showed no increase in expression of
      uspA, grpE, or rpoS, and, as expected, these cells did not exhibit increased
      cryotolerance at -18 degrees C. Knowledge of molecular mechanisms involved in
      cross-protection might make it possible to devise strategies to limit their
      effects and lead to ways to predict the survival of foodborne pathogens in
      stressful environments.

PMID- 15954702
TI  - Influence of dietary vitamin E on behavior of Listeria monocytogenes and color
      stability in ground turkey meat following electron beam irradiation.
AB  - There is growing concern that the free radical scavenging effect of antioxidants
      added to meats might reduce the antimicrobial effectiveness of ionizing
      radiation. A study was conducted to determine the effect of vitamin E on the
      behavior (growth) of Listeria monocytogenes and color stability in turkey meat
      following electron beam irradiation. Raw ground turkey breast meat from birds fed
      diets containing 0 (control), 50, 100, and 200 IU/kg of vitamin E was inoculated
      with a five-strain mixture of L. monocytogenes to give approximately 10(7) CFU/g.
      Inoculated samples were irradiated at 0, 0.5, 1, and 2 kGy and stored aerobically
      (12 days) or under vacuum (42 days) at 4 degrees C. L. monocytogenes survivors
      were determined by plating samples on modified Oxford medium and counting
      colonies on modified Oxford medium plates after 48 h at 35 degrees C. Meat color
      was measured using a colorimeter. Irradiation at 2.0 kGy resulted in an
      approximately 3.5-log reduction of initial numbers of L. monocytogenes. There
      were no significant differences in D-values (decimal reduction times) for L.
      monocytogenes in meat irrespective of vitamin E treatment (P > 0.05). Also,
      vitamin E treatments did not affect growth of the pathogen in aerobic or vacuum
      packaged samples following irradiation (P > 0.05). Compared with controls,
      irradiated meat from birds fed 100 or 200 IU/kg of vitamin E demonstrated
      significant improvement in color stability (lightness and redness values) during
      aerobic storage (P < 0.05). Dietary vitamin E (100 to 200 IU/kg) has good
      potential for improving the color stability of turkey meat without compromising
      the microbial safety of the irradiated product.

PMID- 15954703
TI  - Efficacy of gaseous chlorine dioxide as a sanitizer for killing Salmonella,
      yeasts, and molds on blueberries, strawberries, and raspberries.
AB  - Gaseous chlorine dioxide (ClO2) was tested for its effectiveness in killing
      Salmonella, yeasts, and molds on blueberries, strawberries, and red raspberries.
      An inoculum (100 microl, 6.0 to 6.8 log CFU/g of fruit) that contained five
      serotypes of Salmonella enterica was deposited on the skin, calyx tissue, or stem
      scar tissue of blueberries, skin or stem scar tissue of strawberries, and skin of
      red raspberries, dried for 2 h at 22 degrees C, then held for 20 h at 4 degrees C
      and 2 h at 22 degrees C before treatment. Sachets that contained reactant
      chemicals were formulated to release gaseous ClO2 at concentrations of 4.1, 6.2,
      and 8.0 mg/ liter of air within treatment times of 30, 60, and 120 min,
      respectively, at 23 +/- 1 degrees C. Lethality of ClO2 to Salmonella, yeasts, and
      molds was measured when fruits were in an atmosphere that contained 75 to 90%
      relative humidity. Treatment with 8.0 mg/liter of ClO2 significantly (alpha =
      0.05) reduced the population of Salmonella on blueberries by 2.4 to 3.7 log
      CFU/g. Lethality was higher to cells in inoculum placed on the skin compared with
      the stem scar tissue. Populations of Salmonella on strawberries treated with 8.0
      mg/liter of ClO2 were reduced by 3.8 to 4.4 log CFU/g; a significant reduction of
      1.5 log CFU/g of raspberries was achieved. Treatment with 4.1 to 8.0 mg/liter of
      ClO2 caused reductions in populations of yeast and molds on blueberries,
      strawberries, and raspberries of 1.4 to 2.5, 1.4 to 4.2, and 2.6 to 3.0 log
      CFU/g, respectively. Treatment with 4.1 mg/liter of ClO2 did not markedly affect
      the sensory quality of fruits stored for up to 10 days at 8 degrees C. Results
      indicate that gaseous ClO2 has promise as a sanitizer for small fruits.

PMID- 15954704
TI  - Evaluation of gaseous chlorine dioxide as a sanitizer for killing Salmonella,
      Escherichia coli O157:H7, Listeria monocytogenes, and yeasts and molds on fresh
      and fresh-cut produce.
AB  - Gaseous chlorine dioxide (ClO2) was evaluated for effectiveness in killing
      Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes on fresh-cut
      lettuce, cabbage, and carrot and Salmonella, yeasts, and molds on apples,
      peaches. tomatoes, and onions. Inoculum (100 microl, ca. 6.8 log CFU) containing
      five serotypes of Salmonella enterica, five strains of E. coli O157:H7, or five
      strains of L. monocytogenes was deposited on the skin and cut surfaces of fresh
      cut vegetables, dried for 30 min at 22 degrees C, held for 20 h at 4 degrees C,
      and then incubated for 30 min at 22 degrees C before treatment. The skin surfaces
      of apples, peaches, tomatoes, and onions were inoculated with 100 microl of a
      cell suspension (ca. 8.0 log CFU) containing five serotypes of Salmonella, and
      inoculated produce was allowed to dry for 20 to 22 h at 22 degrees C before
      treatment. Treatment with ClO2 at 4.1 mg/liter significantly (alpha = 0.05)
      reduced the population of foodborne pathogens on all produce. Reductions
      resulting from this treatment were 3.13 to 4.42 log CFU/g for fresh-cut cabbage,
      5.15 to 5.88 log CFU/g for fresh-cut carrots, 1.53 to 1.58 log CFU/g for fresh
      cut lettuce, 4.21 log CFU per apple, 4.33 log CFU per tomato, 1.94 log CFU per
      onion, and 3.23 log CFU per peach. The highest reductions in yeast and mold
      populations resulting from the same treatment were 1.68 log CFU per apple and
      2.65 log CFU per peach. Populations of yeasts and molds on tomatoes and onions
      were not significantly reduced by treatment with 4.1 mg/liter ClO2. Substantial
      reductions in populations of pathogens on apples, tomatoes, and onions but not
      peaches or fresh-cut cabbage, carrot, and lettuce were achieved by treatment with
      gaseous ClO2 without markedly adverse effects on sensory qualities.

PMID- 15954705
TI  - Vibrio vulnificus load reduction in oysters after combined exposure to Vibrio
      vulnificus--specific bacteriophage and to an oyster extract component.
AB  - Oysters infected with Vibrio vulnificus can present a serious health risk to
      diabetic, immunocompromised, and iron-deficient individuals. Numerous studies
      have been conducted with the goal of eliminating this organism from raw oysters.
      We utilized two natural oyster-associated components: pooled Vibrio vulnificus
      specific bacteriophage and an extract of the eastern oyster (Crassostrea
      virginica) that contains an antimicrobial component we named anti-Vibrio
      vulnificus factor, which is bactericidal for V. vulnificus. Although each
      component alone can reduce V. vulnificus numbers independently, the simultaneous
      use of both components in an in vitro system successfully more effectively
      reduced V. vulnificus bacterial loads.

PMID- 15954706
TI  - Ice immersion as a postharvest treatment of oysters for the reduction of Vibrio
      vulnificus.
AB  - Vibrio vulnificus produces serious illnesses that are commonly associated with
      shellfish consumption, particularly raw oysters. Ingestion can result in fatal
      septicemia in susceptible individuals with hepatitis, cirrhosis, immune
      dysfunction, diabetes, or hemochromatosis (metabolic iron overload). Therefore,
      postharvest treatments to reduce vibrio levels in oysters have been recommended.
      In this study, rapid chilling by immersion of unwashed whole oysters in ice for 3
      h was assessed as a postharvest treatment for reduction of V. vulnificus. Treated
      oysters were subsequently refrigerated at 45 degrees F (7.2 degrees C), whereas
      control oysters were not iced but were maintained at 45 degrees F throughout the
      study. Homogenized meats were monitored for total heterotrophic aerobic bacteria,
      V. vulnificus, and fecal coliform content before and after treatment over a 2
      week period. V. vulnificus was enumerated by DNA probe hybridization of colonies
      from standard plate counts on nonselective medium, and recovery was compared for
      several media. Loss of plating efficiency was observed on standard selective and
      differential media compared with nonselective agars. Numbers of V. vulnificus
      generally declined in treated samples compared with controls; however, increases
      in total heterotrophic bacteria and fecal coliforms were also observed in treated
      samples at some time points. This study does not support the use of ice immersion
      as a postharvest method because of the relatively small declines in V. vulnificus
      numbers and the possibility of concomitant increases in fecal coliform and total
      bacterial contamination.

PMID- 15954707
TI  - Outbreak of Escherichia coli O157:H7 infections associated with nonintact blade
      tenderized frozen steaks sold by door-to-door vendors.
AB  - Steaks have not been recognized as an important vehicle of Escherichia coli
      O157:H7 infection. During 11 to 27 June 2003, the Minnesota Department of Health
      (MDH) identified four O157 infection cases with the same pulsed-field gel
      electrophoresis (PFGE) subtype. All four case patients consumed brand A vacuum
      packed frozen steaks sold by door-to-door vendors. The steaks were blade
      tenderized and injected with marinade (i.e., nonintact). Information from single
      case patients in Michigan and Kansas identified through PulseNet confirmed the
      outbreak. The MDH issued a press release on 27 June to warn consumers, prompting
      a nationwide recall of 739,000 lb (335,506 kg) of frozen beef products. The
      outbreak resulted in six culture-confirmed cases (including one with hemolytic
      uremic syndrome) and two probable cases in Minnesota and single confirmed cases
      in four other states. The outbreak PFGE subtype of O157 was isolated from
      unopened brand A bacon-wrapped fillets from five affected Minnesota households. A
      fillet from one affected household was partially cooked in the laboratory, and
      the same O157 subtype was isolated from the uncooked interior. The tenderizing
      and injection processes likely transferred O157 from the surface to the interior
      of the steaks. These processing methods create new challenges for prevention of
      O157 infection. Food regulatory officials should reevaluate safety issues
      presented by nonintact steak products, such as microbiologic hazards of
      processing methods, possible labeling to distinguish intact from nonintact
      steaks, and education of the public and commercial food establishments on the
      increased risk associated with undercooked nonintact steaks. Information on
      single cases of O157 infection in individual states identified through PulseNet
      can be critical in solving multistate outbreaks in a timely manner.

PMID- 15954708
TI  - Modeling the effect of ethanol vapor on the germination time of Penicillium
      chrysogenum.
AB  - The influence of ethanol vapor on germination of Penicillium chrysogenum was
      determined on yeast nitrogen base plus glucose agar medium at 25 degrees C.
      Ethanol vapors were generated by 0 to 6% (wt/wt) ethanol solutions at the bottom
      of hermetically closed petri dishes. The logistic equation was used to describe
      the data as the percentage of germination versus time and to estimate the
      germination time. The effect of ethanol concentration on germination time was
      described by a new reparameterized equation, resulting in an estimated limiting
      ethanol concentration of 4.3%. Up to 3% ethanol, all spores germinated, and the
      germination time increased with increasing ethanol concentration. At 3.5 and 4%,
      some spores formed abnormal germ tubes and others were inhibited at the swelling
      stage. The inhibiting effect of ethanol was reversible under these experimental
      conditions.

PMID- 15954709
TI  - Food protective effect of acaricidal components isolated from anise seeds against
      the stored food mite, Tyrophagus putrescentiae (Schrank).
AB  - The acaricidal activity of anise seed-isolated anisaldehyde and commercially
      available components of anise seed was examined against Tyrophagus putrescentiae
      adults and compared with those of synthetic acaricides, benzyl benzoate, dibutyl
      phthalate, and N,N-diethyl-m-toluamide (DEET). On the basis of LD50 (50% lethal
      dose) values, the compound most toxic to T. putrescentiae adults was anisaldehyde
      (LD50, 0.96 microg/cm2), followed by benzyl benzoate (LD50, 11.3 microg/cm2),
      anethole (LD50, 12.3 microg/cm2), dibutyl phthalate (LD50, 13.3 microg/cm2), DEET
      (LD50, 13.5 microg/cm2), estragole (LD50, 17.4 microg/cm2), and myrcene (LD50,
      56.2 microg/cm2). Anisaldehyde was about 11.8 and 14 times more toxic than benzyl
      benzoate and DEET against T. putrescentiae adults, respectively. The results
      suggested that anisaldehyde, anethole, estragole, and myrcene derived from anise
      seeds are useful as a lead compound to development new agents for selective
      control of the stored food mite.

PMID- 15954710
TI  - Fungal infections of fresh-cut fruit can be detected by the gas chromatography
      mass spectrometric identification of microbial volatile organic compounds.
AB  - There is a large and rapidly growing market for fresh-cut fruit. Microbial
      volatile organic compounds indicate the presence of fungal or bacterial
      contamination in fruit. In order to determine whether microbial volatile organic
      compounds can be used to detect contamination before fruit becomes unmarketable,
      pieces of cantaloupe, apple, pineapple, and orange were inoculated with a variety
      of fungal species, incubated at 25 degrees C, then sealed in glass vials. The
      volatiles were extracted by headspace solid-phase microextraction and analyzed by
      gas chromatography-mass spectrometry. Forty-five compounds were identified that
      might serve as unique identifiers of fungal contamination. Fungal contamination
      can be detected as early as 24 h after inoculation.

PMID- 15954711
TI  - Quantitative detection of species-specific DNA in feedstuffs and fish meals.
AB  - A sensitive and rapid method for the quantitative detection of bovine-, ovine-,
      swine-, and chicken-specific mitochondrial DNA sequences based on real-time PCR
      has been developed. The specificity of the primers and probes for real-time PCR
      has been tested using DNA samples of other vertebrate species that may also be
      present in rendered products. The quantitative detection was performed with dual
      labeled probes (TaqMan) using absolute quantification with external standards of
      single species meat-and-bone meals. This method facilitates the detection of
      0.01% of the target species-derived material in concentrate feed mixtures and
      fish meals.

PMID- 15954712
TI  - Assessment of the effects of Nurmi-type cultures and a defined probiotic
      preparation on a Salmonella typhimurium 29E challenge in vivo.
AB  - The effects of treatment with an undefined commercial Nurmi-type culture (NTC),
      cultured cecal contents, and a dual-strain probiotic, containing Enterococcus
      faecalis and Pediococcus pentosaceus, on Salmonella Typhimurium colonization were
      evaluated in a specific-pathogen-free bird model. Two sets of trials were
      performed, and each study was arranged as a randomized complete block design with
      three treatments. Treatments consisted of (i) control, (ii) commercial NTC, and
      (iii) cultured cecal contents in the first set of trials and (i) control, (ii)
      defined probiotic, and (iii) cultured cecal contents in the second set. On day 1,
      birds were administered 1.2 x 10(7) CFU of the appropriate treatment by oral
      gavage. On day 3, all birds were challenged with 1 x 10(6) CFU of Salmonella
      Typhimurium 29E (nalidixic acid resistant). Chicks were asphyxiated with argon
      gas on day 10, and ceca were aseptically removed. Salmonella Typhimurium counts
      (CFU per milliliter of cecal contents) were determined on brilliant green agar
      containing 30 mg of nalidixic acid per liter, and CFU counts were log transformed
      prior to analysis. Cecal pH and volatile fatty acid concentrations were also
      determined. Data were analyzed by one-way analysis of variance, and means were
      compared by Tukey's pairwise analysis. Commercial NTC and cultured cecal contents
      treatments resulted in a significant decrease (P < or = 0.05) in Salmonella
      Typhimurium 29E colonization, with the NTC offering a higher level of protection.
      In the second set of trials, the defined probiotic tended to reduce colonization
      by Salmonella Typhimurium (P = 0.07), while chicks treated with cultured cecal
      contents displayed a significant decrease (P = 0.03) when compared to the
      negative control. No significant change was observed in cecal pH or in acetate
      and propionate concentrations; however, a significant increase in butyrate
      concentrations in both the cultured cecal contents and defined probiotic
      treatment groups was observed when compared to the control birds. These
      observations suggest that defined cultures are less effective Salmonella control
      agents than are preparations generated from the complete cecal microflora.

PMID- 15954713
TI  - Raw and processed fish show identical Listeria monocytogenes genotypes with
      pulsed-field gel electrophoresis.
AB  - A total of 257 raw fish samples at two different sites were examined for the
      presence of Listeria monocytogenes. The prevalence of L. monocytogenes was 4%.
      From 11 positive samples, nine different L. monocytogenes pulsed-field gel
      electrophoresis genotypes were recovered. From nine pulsotypes recovered from raw
      fish and 32 pulsotypes shown by 101 fish product isolates, two raw fish and fish
      product pulsotypes were indistinguishable from each other. Although the
      prevalence of L. monocytogenes in raw fish is low, the range of L. monocytogenes
      strains entering the processing plant in large amounts of raw material is wide.
      This indicates that the raw material is an important initial contamination source
      of L. monocytogenes in fish processing plants. This postulation is supported by
      the identical pulsotypes recovered from both raw and processed fish. Some L.
      monocytogenes strains entering a plant may thus contaminate and persist in the
      processing environment, causing recurrent contamination of the final products via
      processing machines.

PMID- 15954714
TI  - Inactivation of Pseudomonas fluorescens in skim milk by combinations of pulsed
      electric fields and organic acids.
AB  - Pseudomonas fluorescens suspended in skim milk was inactivated by application of
      pulsed electric fields (PEF) either alone or in combination with acetic or
      propionic acid. The initial concentration of microorganisms ranged from 10(5) to
      10(6) CFU/ml. Addition of acetic acid and propionic acid to skim milk inactivated
      0.24 and 0.48 log CFU/ml P. fluorescens, respectively. Sets of 10, 20, and 30
      pulses were applied to the skim milk using exponentially decaying pulses with
      pulse lengths of 2 micros and pulse frequencies of 3 Hz. Treatment temperature
      was maintained between 16 and 20 degrees C. In the absence of organic acids, PEF
      treatment of skim milk at field intensities of 31 and 38 kV/cm reduced P.
      fluorescens populations by 1.0 to 1.8 and by 1.2 to 1.9 log CFU/ml, respectively.
      Additions of acetic and propionic acid to the skim milk in a pH range of 5.0 to
      5.3 and PEF treatment at 31, 33, and 34 kV/cm, and 36, 37, and 38 kV/cm reduced
      the population of P. fluorescens by 1.4 and 1.8 log CFU/ml, respectively. No
      synergistic effect resulted from the combination of PEF with acetic or propionic
      acid.

PMID- 15954715
TI  - Evaluation of gaseous ozone and hydrogen peroxide treatments for reducing
      Fusarium survival in malting barley.
AB  - The use of Fusarium-infected barley for malting can lead to mycotoxin production
      and decreased malt quality. Methods for treatment of Fusarium-infected barley
      might prevent these safety and quality defects and allow use of otherwise good
      quality barley. Gaseous ozone and hydrogen peroxide (HP) were evaluated for
      effectiveness in reducing Fusarium survival while maintaining germinative energy
      (GE) in barley. Gaseous ozone treatments (GOT) included concentrations of 11 and
      26 mg/g for 0, 15, 30, and 60 min. HP treatments included 0, 5, 10, and 15%
      concentrations with exposure times of 0, 5, 10, 15, 20, and 30 min. For GOT, in
      naturally Fusarium-infected barley, a statistically significant (P < 0.05)
      decrease (24 to 36%) of Fusarium survival occurred within 15 min of exposure at
      either concentration. GE was significantly (P < 0.05) affected by 30 min at both
      concentrations in naturally Fusarium-infected barley, but not in sound barley.
      GOT did not cause any significant (P > 0.05) effect on GE in sound barley at
      either concentration over the full 30-min exposure time. For HP, Fusarium
      survival was significantly decreased (50 to 98%) within 5 min of exposure. With
      the exception of two treatments (10 and 15% HP agitated for 20 min), GE was not
      statistically significantly different from the control in naturally Fusarium
      infected barley. In sound barley, HP had no significant (P > 0.05) effect on GE.
      The results suggest that GOT and HP might have potential for treatment of
      Fusarium-infected malting barley.

PMID- 15954716
TI  - Quantum dots as fluorescent labels for quantitative detection of Salmonella
      typhimurium in chicken carcass wash water.
AB  - Fluorescent semiconductor quantum dots have recently emerged as a novel and
      promising class of fluorescent labels for biological detection. In this study,
      quantum dots were used as fluorescent labels in immunoassays for quantitative
      detection of foodborne pathogenic bacteria. Salmonella Typhimurium cells were
      separated from chicken carcass wash water using anti-Salmonella antibody coated
      magnetic beads and reacted to secondary biotin-labeled anti-Salmonella antibody.
      Quantum dots coated with streptavidin were added to react with biotin on the
      secondary antibody. Measurement of the intensity of fluorescence produced by
      quantum dots provided a quantitative method for microbial detection. A linear
      relationship between Salmonella Typhimurium cell number (log N) in the samples of
      chicken carcass wash water and the fluorescence intensity (FI) was found for the
      cell numbers ranging from 10(3) to 10(7) CFU/ml. The regression model can be
      expressed as FI = 198.6 Log N - 639.03 with R2 = 0.96. The detection limit of
      this method was 10(3) CFU/ml.

PMID- 15954717
TI  - Raffinose family of oligosaccharides from lupin seeds as prebiotics: application
      in dairy products.
AB  - The raffinose family of oligosaccharides (RFOs) isolated from lupin seeds
      (Lupinus albus var. Multolupa) was evaluated for bifidogenic effects during the
      manufacture of probiotic fermented milk. A mixed starter inoculum was composed of
      Bifidobacterium lactis Bb-12 and Lactobacillus acidophilus (1:1). Lupins are a
      rich source of RFOs that can be used as functional food ingredients. The addition
      of RFOs to milk increased B. lactis Bb-12 and L. acidophilus populations at the
      final fermentation time compared with controls. Final fermentation products are
      positively affected by addition of RFOs, and time of fermentation was reduced
      from 12 to 10 h. When RFOs were added to milk, they were preferentially used as a
      carbon source (57.7%) compared with lactose (23.7%) at the end of fermentation.
      These results suggest that the eventual choice of B. lactis Bb-12 and L.
      acidophilus in a mixed culture at a 1:1 ratio and addition of RFOs to produce a
      fermented milk product would have the advantages of rapid growth and
      acidificationrate and would likely increase the probiotic effect of the final
      functional product.

PMID- 15954718
TI  - Science and technology based countermeasures to foodborne terrorismt:
      introduction.

PMID- 15954719
TI  - Methods for detection of Clostridium botulinum toxin in foods.
AB  - Botulism is a deadly disease caused by ingestion of the preformed neurotoxin
      produced from the anaerobic spore-forming bacteria Clostridium botulinum.
      Botulinum neurotoxins are the most poisonous toxins known and have been a concern
      in the food industry for a long time. Therefore, rapid identification of
      botulinum neurotoxin using molecular and biochemical techniques is an essential
      component in the establishment of coordinated laboratory response systems and is
      the focus of current research and development. Because of the extreme toxicity of
      botulinum neurotoxin, some confirmatory testing with the mouse bioassay is still
      necessary, but rapid methods capable of screening large numbers of samples are
      also needed. This review is focused on the development of several detection
      methods for botulinum neurotoxins in foods.

PMID- 15954720
TI  - Staphylococcal enterotoxin and its rapid identification in foods by enzyme-linked
      immunosorbent assay-based methodology.
AB  - The problem of Staphylococcus aureus and other species as contaminants in the
      food supply remains significant on a global level. Time and temperature abuse of
      a food product contaminated with enterotoxigenic staphylococci can result in
      formation of enterotoxin, which can produce foodborne illness when the product is
      ingested. Between 100 and 200 ng of enterotoxin can cause symptoms consistent
      with staphylococcal intoxication. Although humans are the primary reservoirs of
      contamination, animals, air, dust, and food contact surfaces can serve as
      vehicles in the transfer of this pathogen to the food supply. Foods may become
      contaminated during production or processing and in homes or food establishments,
      where the organism can proliferate to high concentrations and subsequently
      produce enterotoxin. The staphylococcal enterotoxins are highly heat stable and
      can remain biologically active after exposure to retort temperatures. Prior to
      the development of serological methods for the identification of enterotoxin,
      monkeys (gastric intubation) and later kittens (intravenous injection) were used
      in assays for toxin detection. When enterotoxins were identified as mature
      proteins that were antigenic, serological assays were developed for use in the
      laboratory analysis of foods suspected of containing preformed enterotoxin. More
      recently developed methods are tracer-labeled immunoassays. Of these methods, the
      enzyme-linked immunosorbent assays are highly specific, highly sensitive, and
      rapid for the detection of enterotoxin in foods.

PMID- 15954721
TI  - Chips and SNPs, bugs and thugs: a molecular sleuthing perspective.
AB  - Recent events both here and abroad have focused attention on the need for
      ensuring a safe and secure food supply. Although much has been written about the
      potential of particular select agents in bioterrorism, we must consider seriously
      the more mundane pathogens, especially those that have been implicated previously
      in foodborne outbreaks of human disease, as possible agents of bioterrorism.
      Given their evolutionary history, the enteric pathogens are more diverse than
      agents such as Bacillus anthracis, Francisella tularensis, or Yersinia pestis.
      This greater diversity, however, is a double-edged sword; although diversity
      affords the opportunity for unequivocal identification of an organism without the
      need for whole-genome sequencing, the same diversity can confound definitive
      forensic identification if boundaries are not well defined. Here, we discuss
      molecular approaches used for the identification of Salmonella enterica,
      Escherichia coli, and Shigella spp. and viral pathogens and discuss the utility
      of these approaches to the field of microbial molecular forensics.

PMID- 15954722
TI  - Threat assessment of mycotoxins as weapons: molecular mechanisms of acute
      toxicity.
AB  - Mycotoxins are impractical as tactical weapons, butthey can be used by small poor
      terrorist organizations to poison food and water sources or can be released in
      crowded, confined areas. Crude concentrated or dried extracts of readily grown
      fungal cultures can be used as weapons. The production of fungal weapons does not
      require elaborate facilities for the growth of fungi, sophisticated equipment for
      the purification of the toxins, or highly trained personnel. Aflatoxin B1,
      fumonisin B1, ochratoxin A, and the trichothecenes T-2 toxin and deoxynivalenol
      could be weaponized for bioterrorism. Knowledge of the symptoms of intoxication
      and the biochemical mechanisms of action of mycotoxins is necessary for the rapid
      identification of the toxins, the development of prophylactic antidotes, and the
      design of effective treatments of affected persons. All of these mycotoxins
      except deoxynivalenol are carcinogens (Stark, A. A., Annu. Rev. Microbiol. 34:235
      262, 1980; Stark, A. A., p. 435-445, in P. S. Steyn and R. Vleggaar, ed.,
      Mycotoxins and phycotoxins, 1986; Stark, A. A., p. 47-60, in C. L. Wilson and S.
      Droby, ed., Microbial food contamination, 2000; Stark, A. A., and N. Paster, p.
      60-64, in M. L. Wahlqvist, A. S. Truswell, R. Smith, and P. L. Nestel, ed.,
      Nutrition in a sustainable environment, 1994). Because immediate and widespread
      death, illness, or panic is the goal of bioterrorists, the mechanisms by which
      mycotoxins exert acute toxicity are the focus of this article.

PMID- 15954723
TI  - Feasibility of immunodiagnostic devices for the detection of ricin, amanitin, and
      T-2 toxin in food.
AB  - Qualitative and quantitative comparisons were conducted of commercially available
      immunodiagnostic devices for the detection of three select agents with oral LD50
      values > or = 0.1 mg/kg of body weight. Ricin (oral LD50 > 1 mg/kg), amanitin
      (oral LD50 approximately 0.1 mg/kg), and T-2 toxin (oral LD50 > 1 mg/kg) were
      spiked into beverages, produce, dairy, and baked goods and assayed using
      commercially available enzyme-linked immunosorbent assays (ELISAs) and lateral
      flow devices. In all cases, the commercial diagnostic kits successfully detected
      all three select agents at concentrations below what might be a health concern.
      The considerable difference between the limit of detection of the
      immunodiagnostic devices employed (typically < or = 0.020 microg/g) and the
      amount of the select agent necessary to pose a health threat in a single serving
      of food facilitated the design of protocols for the high throughput screening of
      food samples. These protocols entailed simple extraction methods followed by
      sample dilution. Lateral flow devices and sandwich ELISAs for the detection of
      ricin had no significant background problems due to the food matrices.
      Competitive ELISAs, which typically have unacceptably high background reactions
      with food samples, successfully detected amanitin and T-2 toxin.

PMID- 15954724
TI  - Risk assessment of malicious biocontamination of food.
AB  - Throughout the last decades of the 20th century, the biological threat evolved
      from primarily a government-controlled weapon to a tool of terrorism. One of the
      consequences of this trend is the near impossibility of foreseeing when and how
      an act of bioterrorism will occur. The suitability of food products for such an
      act stems from the multitude of microorganisms that may be used for contamination
      and the vulnerability of the products during and after processing. Tests that
      would enable the detection of a large variety of microorganisms quickly,
      reliably, and economically should also provide satisfactory means to prevent acts
      of malicious biocontamination of food products. Until such means become
      available, a priority-based approach to the problem is probably the most
      practical. Priorities should be determined based on a systematic risk assessment
      to define the relative likelihood of a certain microorganism being used in an act
      of malicious food contamination. Criteria to be evaluated are availability,
      weaponization processes, delivery of an effective dose, probability of early
      detection, and the microorganism's resistance to the conditions to which it will
      be exposed. Because the results of such an assessment may vary according to
      prevailing conditions, the assessment must be based on the existing
      circumstances. The results of the assessment should then be applied to the
      various procedures of food processing, which should further reduce the number of
      potential microbial threats. Existing methods of screening food for contaminating
      microorganisms and existing food safety and security procedures such as hazard
      analysis and critical control point programs may have to be modified to become
      suitable for the detection of acts of bioterrorism.

PMID- 15954725
TI  - Sampling uncertainties for the detection of chemical agents in complex food
      matrices.
AB  - Using uncertainty associated with detection of aflatoxin in shelled corn as a
      model, the uncertainty associated with detecting chemical agents intentionally
      added to food products was evaluated. Accuracy and precision are two types of
      uncertainties generally associated with sampling plans. Sources of variability
      that affect precision were the primary focus of this investigation. Test
      procedures used to detect chemical agents generally include sampling, sample
      preparation, and analytical steps. The uncertainty of each step contributes to
      the total uncertainty of the test procedure. Using variance as a statistical
      measure of uncertainty, the variance associated with each step of the test
      procedure used to detect aflatoxin in shelled corn was determined for both low
      and high levels of contamination. For example, when using a 1-kg sample, Romer
      mill, 50-g subsample, and high-performance liquid chromatography to test a lot of
      shelled corn contaminated with aflatoxin at 10 ng/g, the total variance
      associated with the test procedure was 149.2 (coefficient of variation of
      122.1%). The sampling, sample preparation, and analytical steps accounted for
      83.0, 15.6, and 1.4% of the total variance, respectively. A variance of 149.2
      suggests that repeated test results will vary from 0 to 33.9 ng/g. Using the same
      test procedure to detect aflatoxin at 10,000 ng/g, the total variance was 264,719
      (coefficient of variation of 5.1%). The sampling, sample preparation, and
      analytical steps accounted for 41, 57, and 2% of the total variance,
      respectively. A variance of 264,719 suggests that repeated test results will vary
      from 8,992 to 11,008 ng/g. Foods contaminated at low levels reflect a situation
      in which a small percentage of particles is contaminated and sampling becomes the
      largest source of uncertainty. Large samples are required to overcome the "needle
      in-the-haystack" problem. Aflatoxin is easier to detect and identify in foods
      intentionally contaminated at high levels than in foods with low levels of
      contamination because the relative standard deviation (coefficient of variation)
      decreases and the percentage of contaminated kernels increases with an increase
      in concentration.

PMID- 15954726
TI  - Authentication, antitamper, and track-and-trace technology options to protect
      foods.
AB  - Many security technologies (Anonymous, Effective supply chain protection, 2002)
      have been developed to protect a wide range of products, documents, and
      individuals. The food industry has very specialized needs, and food products may
      be affected by criminal activities such as tampering, relabeling, unauthorized
      diversion, and counterfeiting. It is important to understand the attributes
      associated with security technologies so that the benefits may be weighed against
      the restrictions that arise when selecting appropriate solutions to protect the
      food supply chain. Security technology may be split into a number of categories:
      authentication, coding, tamper evidence, and tracking. Within each category the
      technology may be subdivided into overt, covert, and forensic features. No single
      technology provides an infallible solution to all problems, so the most enduring
      and effective solutions almost always comprise a combination of technologies that
      provide deterrence, aid detection, and assist with subsequent prosecution of
      perpetrators.

PMID- 15954727
TI  - Pay for performance: is this the cure for Medicare's ills?

PMID- 15954728
TI  - [Patient with intestinal suboclusion syndrome].

PMID- 15954730
TI  - [CD11b-positive cells expression in rectal mucosa from ovalbumin sensitized and
      challenged rabbits].
AB  - Rabbit MAC-1 receptor, homologue to human CD11b is present in macrophages. The
      aim of the study was to determine quantitative and distributive modifications of
      CD11b-positive cells that participate in immune response at rectal mucosa, in an
      animal model of mucosal immunity. New Zealand rabbits were divided into three
      groups. G1: control; G2: ovalbumin (OVA) sensitized; G3: OVA-senstitized and
      rectal challenged. Animals were subcutaneously sensitized twice with 70 microg
      OVA and 30 ml aluminium hydroxide in 2 ml saline solution. Rectal challenge was
      developed with a solution of 50 mg OVA in 5 ml saline solution. Sensitized groups
      (G2 and G3) showed a positive PCA (Passive Cutaneous Anaphylaxis) at 1/160 fold
      dilutions. In G3 we observed a patchy mucosal edema, lymphangiectasis and
      eosinophil leucocyte infiltration. Cells were counted as the number of cells per
      high power field. G1: 9.64 (SE 0.22); G2: 18.10 (SE 0.09) and G3: 23.60 (SE
      0.29). (G2 vs G1 p < 0.001; G3 vs G1 p < 0.001; G3 vs G2 p < 0.001). We conclude
      that there is a close relationship between the food antigen OVA penetration
      (after challenge) and the increase of CD11b positive cells in rectal mucosa. This
      fact could be due to the cellular influx to the inflammatory site by the action
      of chemotactic factors released after challenge.

PMID- 15954731
TI  - Increased oxygen consumption caused by cAMP- and Ca(2+)-mediated chloride
      secretion in rat distal colon.
AB  - Epithelial ion transport is dependent on ATP supply provided by aerobic
      metabolism. In the rat distal colon chloride secretion accounts for the largest
      portion of electrogenic transport measured as the short-circuit current (I(SC)).
      Inhibition of basal chloride secretion decreases epithelial oxygen consumption
      (QO2) in this tissue, while serotonin (5-hydroxytryptamine) proportionally
      increases both Isc and QO2. The effect of serotonin in this tissue is mainly
      mediated by 5HT4 receptors linked to adenylate cyclase through a stimulant G
      protein (GS). This work assessed whether the chloride secretion-induced increase
      in QO2 is a common characteristic of secretagogues, which act through either cAMP
      dependent or Ca(2+)-dependent mechanisms. The effects of phosphodiesterase
      inhibitor 3-isobutyl-1-methylxantine (IBMX) and muscarinic agonist carbachol
      (both 0.1 mmol/L) were studied in rat distal colon isolated mucosa mounted in an
      Ussing chamber adapted for continuous measurement of oxygen concentration,
      allowing determination of QO2. Baseline I(SC) and QO2 were compared with I(SC)
      and QO2 after addition of either serotonin as an active control, IBMX, carbachol
      or IBMX plus carbachol. Each drug increased proportionally Isc and QO2. Although
      the effect of IBMX alone was modest and that of carbachol was short-lived, a
      synergic effect on Isc and QO2 was seen when both drugs were simultaneously
      added. Linear regression analysis showed a significant correlation between
      increases in I(SC) and QO2 (r2 = 0.746; P < 0.0001). Thus, stimulation of
      chloride secretion increases QO2 regardless of the intracellular pathway
      involved. These results extend previous findings, corroborating the close
      coupling between chloride secretion and QO2 in this epithelium.

PMID- 15954732
TI  - [Gastric antral vascular ectasia:clinical presentation and therapeutic
      management].
AB  - The gastric antral vascular ectasia (GAVE) or watermelon stomach is an
      increasingly recognized cause of persistent upper gastrointestinal bleeding,
      which has typical endoscopic and histological findings. This disease is most
      frequent in elderly women, and several associated conditions have been well
      established. Some patients with severe portal hypertensive gastropathy may have a
      GAVE like appearence. Nevertheless, a correct diagnosis is relevant in order to
      choose an appropiate treatment. The objective of the current study is to analyze
      the clinical features and treatment of a group of patients with GAVE evaluated at
      our Institution. A review of the current literature was also performed. Six women
      and three men with GAVE were admitted at the Buenos Aires British Hospital
      between November 1998 and January 2004. Endoscopic biopsy was performed in eight
      patients and was consistent with GAVE in all cases. Four patients with chronic
      anaemia as unique manifestation were successfully treated with iron supplements.
      Endoscopic treatment was performed in 4 patients, 3 of them were treated with
      bipolar electrocautery and 1 with argon plasma coagulation. An antrectomy was
      carried out in the ninth patient. The resolution of the bleeding was observed in
      all cases with the different therapeutics options used.

PMID- 15954733
TI  - [Gastro-duodenal trichobezoars: a rare cause of obstruction of the
      gastrointestinal tract].
AB  - BACKGROUND: Trichobezoars represent 55% of human bezoars. Patients are women in
      90% of cases and have some psychiatric disorder in 40%. OBJECTIVE: To study the
      clinical features, diagnostic methodology and treatment in patients with
      trichobezoars. DESIGN: Retrospective analysis of clinical records and case
      report. METHOD: Four patients were included between January 2000 and March 2004,
      3 women and 1 man, with a mean age of 32.3 years (range 22 to 73 years). RESULTS:
      All patients had an epigastric mass, dyspepsia, vomiting, and weight loss of 5 to
      25 kg, without pain. Three patients underwent barium studies, and all of them
      ultrasonography, computerized tomography and upper gastrointestinal endoscopy.
      All of them received endoscopic procedures without treatment success. Any patient
      referred trichophagy and all of them had psychiatric disorders. The surgical
      treatment was gastrotomy and removal of the bezoar. The average weight was 1,100
      g (range 700 to 1,500 g). CONCLUSIONS: The trichobezoar is a rare cause of
      obstruction of the gastrointestinal tract. The diagnosis should be suspected with
      the clinical and barium study findings, and confirmed by computerized tomography
      and endoscopy. Surgery is the treatment of choice. However, other treatments have
      been described, such as endoscopic fragmentation, extracorporeal lithotripsy and
      laparoscopic extraction.

PMID- 15954734
TI  - [Activity index in Crohn's disease].
AB  - The gold standard to quantify Crohn's disease activity is still not defined and a
      world consensus to unify criteria is necessary. Criticism has been directed
      towards every existing indexes. We summarize some of the currently used criteria
      for the assessment of disease activity, point out the controversies and issues
      that will need further investigations, and discuss their usefulness based on our
      experience.

PMID- 15954735
TI  - The world map of celiac disease.

PMID- 15954736
TI  - [Antibiotic prophylaxis in acute pancreatitis: a still open controversy].

PMID- 15954737
TI  - [Percutaneous management of the biliary tract].

PMID- 15954738
TI  - Biosensors for heavy metals.
AB  - A biosensor is an analytical device that consists of an immobilized biocomponent
      in conjunction with a transducer, and represents a synergistic combination of
      biotechnology and microelectronics. This review summarizes the use of biosensors
      for detecting and quantifying heavy metal ions. Heavy metal contamination is of
      serious concern to human health since these substances are non-biodegradable and
      retained by the ecological system. Conventional analytical techniques for heavy
      metals (such as cold vapour atomic absorption spectrometry, and inductively
      coupled plasma mass spectrometry) are precise but suffer from the disadvantages
      of high cost, the need for trained personnel and the fact that they are mostly
      laboratory bound. Biosensors have the advantages of specificity, low cost, ease
      of use, portability and the ability to furnish continuous real time signals. The
      analysis of heavy metal ions can be carried out with biosensors by using both
      protein (enzyme, metal-binding protein and antibody)-based and whole-cell
      (natural and genetically engineered microorganism)-based approaches.

PMID- 15954739
TI  - Susceptibility of insulinoma cells to cadmium and modulation by L-type calcium
      channels.
AB  - Cadmium (Cd), a toxic metal that induces apoptosis and necrosis in a variety of
      cells, accumulates in pancreas and may be a cause of diabetes in humans. In the
      insulinoma cells line HIT-T15 (HIT), we measured internal calcium (Ca) and Cd
      levels by the fluorescent dye Fura-2 and confirm that L-type voltage-dependent
      calcium channels (VDCC) play a major role in glucose response and represent a
      pathway of Cd influx in these cells. Therefore we examined the role of VDCC in
      acute Cd poisoning by comparing its accumulation and cytotoxic effect in HIT
      cells and in epithelial-like VDCC-free HeLa cells. Cultures were incubated with
      10-300 microM Cd for 15 min-6 h. While negligible at the end of the treatment,
      HIT cell death was evident after 18-24 h, and it was time-, dose- and serum
      dependent. Short (< or = 60 min) Cd treatments with lower doses (< or = 100
      microM in serum-free medium) induced delayed apoptotic cell death, as
      demonstrated by DNA fragmentation on agarose gels and segmentation of DAPI
      stained nuclei. Longer incubations and/or higher concentrations caused mainly
      necrosis. The same treatments were largely harmless in HeLa cells, in which
      neither death nor DNA fragmentation was observed. The Ca antagonist nimodipine
      was capable to prevent HIT cell death at lower doses of Cd and to restore the
      apoptotic condition at higher doses, indicating that reduction of Cd flux through
      VDCC modulates Cd toxicity. These data demonstrate a specific sensitivity to Cd
      of insulinoma cells that can be significant for pancreatic beta-cell pathology.

PMID- 15954740
TI  - Studies on structure activity relationship of some dihydroxy-4-methylcoumarin
      antioxidants based on their interaction with Fe(III) and ADP.
AB  - Three dihydroxy-4-methylcoumarin (DHMC) derivatives, namely 7,8-DHMC, 6,7-DHMC
      and 5,7-DHMC alone and complexed with Fe(III) and ADP have been tested for their
      antioxidative potential. Chemical speciation studies and formation constants
      reveal the formation of strong DHMC-Fe-ADP (1:1:1) ternary complex. In vitro
      studies were done for their antioxidative property by scavenging the superoxide
      radicals (O2*-) generated by xanthine + xanthine oxidase (XO) reaction. The IC50
      values for 7,8-DHMC, 6,7-DHMC and 5,7-DHMC and their ternary complexes with
      Fe(III)-ADP worked out to be 34.0 microM, 62.0 microM, 8.80 mM and 10.5, 11.5 and
      148.5 microM, respectively. The results indicate that O2*- scavenging potential
      of all the three DHMCs increased significantly after forming the ternary complex
      with Fe(III) and ADP. The structure activity relationship studies suggest that
      the introduction of hydroxyl group at 7th and 8th positions in the coumarins,
      irrespective of Fe(III)-ADP complexation, increases the antioxidative efficacy.
      No change in uric acid production in the reactions done for all studies further
      reveals that the coumarin derivatives and their complexes were the only causative
      factors for O2*- scavenging and not the suppression of the enzyme, xanthine
      oxidase.

PMID- 15954741
TI  - A comparative evaluation of the biological effects of environmental cadmium
      contaminated control diet and laboratory-cadmium supplemented test diet.
AB  - This study was designed to examine the effects of a diet contaminated by
      environmental cadmium on organ/body weight ratio and selected toxicological
      indices. It was also designed to permit a comparative analysis of the effects of
      the diet contaminated by environmental cadmium and that of cadmium supplemented
      diet based on the same parameters. Our results show that even though the cadmium
      content of the environmental cadmium contaminated diet was 300% less than that of
      the cadmium supplemented diet, the former caused statistically significant
      changes in Superoxide dismutase (SOD) activity (P < 0.025), Na+/K+ ATPase
      activity (P < 0.005) and Malondialdehyde (MDA) level (P < 0.025) when values at
      the end of 1 month exposure were compared to the values at the end of 3 months
      exposure. These parameters were altered in the same manner by the cadmium content
      of the supplemented diet in addition to significant reduction in liver/body
      weight ratio (P < 0.005) within the exposure periods examined. By virtue of the
      very close nature of the values of these parameters in rats exposed to the two
      different diets, it appears that the background cadmium (cadmium from the
      environment) content of the diets is largely responsible for the observed
      changes, except in the case of liver/body weight ratio.

PMID- 15954742
TI  - Myocardial content of selected elements in experimental anthracycline-induced
      cardiomyopathy in rabbits.
AB  - Cardiotoxicity represents the main drawback of clinical usefulness of
      anthracycline antineoplastic drugs. In this study, a content of selected elements
      (Ca, Mg, K, Se, Fe) in the post-mortem removed samples of the myocardial tissue
      was studied in three groups of rabbits: 1) control group (i.v. saline; n = 10);
      2) daunorubicin-receiving animals (DAU; 3 mg/kg, i.v; n = 11); 3) animals
      receiving cardioprotective iron-chelating agent dexrazoxane (DEX; 60 mg/kg, i.p.;
      n = 5) prior to DAU. Drugs were administered once weekly for 10 weeks. 5-7 days
      after the last administration, cardiac left ventricular contractility (dP/dtmax)
      was significantly decreased in DAU-treated animals (745 +/- 69 versus 1245 +/- 86
      kPa/s in the control group; P < 0.05), while in the DEX + DAU group it was
      insignificantly increased (1411 +/- 77 kPa/s). Of the myocardial elements'
      content studied, a significant increase in total Ca against control (16.2 +/- 2.4
      versus 10.6 +/- 0.9 microg/g of dry tissue; P < 0.05) was determined in the DAU
      group, which was accompanied with significant decreases in Mg and K. In the heart
      tissue of DEX-pretreated animals, no significant changes of elements' content
      were found as compared to controls, while the Ca content was in these animals
      significantly lower than in the DAU group (9.1 +/- 0.4 versus 16.2 +/- 2.4
      microg/g; P < 0.05). Hence, in this study we show that systolic heart failure
      induced by chronic DAU administration is primarily accompanied by persistent
      calcium overload of cardiac tissue and the protective action of DEX is associated
      with the restoration of normal myocardial Ca content.

PMID- 15954743
TI  - Stability, protein binding and thiol interaction studies on [2-acetoxy-(2
      propynyl)benzoate]hexacarbonyldicobalt.
AB  - Cobalt-alkyne complexes are a new class of potent cytotoxic drugs. The lead
      compound [2-acetoxy-(2-propynyl)benzoate]hexacarbonyldicobalt (Co-ASS) showed
      high effects on several human cancer cell lines. In order to evaluate further the
      in-vitro properties and reactivity of this substance we performed stability and
      protein binding studies and investigated the interaction of this complex with 1,2
      ethanedithiol, L-cysteine and glutathione. UV-Vis, HPLC and AAS studies showed
      that the compound was sufficiently stable under in-vitro conditions. Binding to
      human serum albumin increased from approximately 25% at the beginning to over 50%
      after 48 h of incubation as determined by ethanol preciptation and size exclusion
      chromatography. The interaction with thiols resulted in disulfide bond formation
      of the thiols.

PMID- 15954744
TI  - Heavy metal interference with growth hormone signalling in trout hepatoma cells
      RTH-149.
AB  - We have studied the effects of heavy metals (Hg2+, Cu2+, Cd2+) on growth hormone
      (GH) activation of tyrosine kinase and Ca2+ signaling in the trout (Oncorhynchus
      mykiss) hepatoma cell line RTH-149. Molecular cloning techniques using primer
      designed on Oncorhynchus spp. growth hormone receptor (GHR) genes allowed to
      isolate a highly homologous cDNA fragment from RTH-149 mRNA. Thereafter, cells
      were analysed by Western blotting or, alternatively, with Ca2+ imaging using fura
      2/AM. Exposure of cells to ovine GH alone produced a stimulation of the
      JAK2/STAT5 pathway and intracellular free Ca2+ variations similar to what has
      been observed in mammalian models. Cell pre-exposure to Cu2+, Hg2+ or Cd2+
      affected cell response to GH by enhancing (Cu2+) or inhibiting (Cd2+) the
      phosphorylation of JAK2 and STAT5. Heavy metals induced the activation of the MAP
      kinase p38, and pre-exposure to Hg2+ or Cu2+ followed by GH enhanced the effect
      of metal alone. Image analysis of fura2-loaded cells indicated that pre-treatment
      with Hg2+ prior to GH produced a considerable increase of the [Ca2+]i variation
      produced by either element, while using Cu2+ or Cd2+ the result was similar but
      much weaker. Data suggest that heavy metals interfere with GH as follows: Hg2+ is
      nearly ineffective on JAK/STAT and strongly synergistic on Ca2+ signaling; Cu2+
      is activatory on JAK/STAT and slightly activatory on Ca2+; Cd2+ is strongly
      inhibitory on JAK/STAT and slightly activatory on Ca2+; heavy metals could
      partially activate STAT via p38 independently from GH interaction.

PMID- 15954745
TI  - Characterization of iron compounds in tumour tissue from temporal lobe epilepsy
      patients using low temperature magnetic methods.
AB  - Excess iron accumulation in the brain has been shown to be related to a variety
      of neurodegenerative diseases. However, identification and characterization of
      iron compounds in human tissue is difficult because concentrations are very low.
      For the first time, a combination of low temperature magnetic methods was used to
      characterize iron compounds in tumour tissue from patients with mesial temporal
      lobe epilepsy (MTLE). Induced magnetization as a function of temperature was
      measured between 2 and 140 K after cooling in zero-field and after cooling in a
      50 mT field. These curves reveal an average blocking temperature for ferritin of
      10 K and an anomaly due to magnetite at 48 K. Hysteresis measurements at 5 K show
      a high coercivity phase that is unsaturated at 7 T, which is typical for
      ferritin. Magnetite concentration was determined from the saturation remanent
      magnetization at 77 K. Hysteresis measurements at various temperatures were used
      to examine the magnetic blocking of magnetite and ferritin. Our results
      demonstrate that low temperature magnetic measurements provide a useful and
      sensitive tool for the characterisation of magnetic iron compounds in human
      tissue.

PMID- 15954746
TI  - Can industry spread its green fever?

PMID- 15954748
TI  - Pitfalls for parents.

PMID- 15954747
TI  - The big pill pitch.

PMID- 15954749
TI  - "Volatilizable" supports for high-throughput organic synthesis.
AB  - The concepts and use of "volatilizable" solid supports are presented. Such
      supports, which are completely removed by volatilization following decomposition,
      improve the efficiency of the solid-phase synthesis of both individual and
      mixtures of low-molecular weight acyclic and heterocyclic compounds as well as
      peptides, peptidomimetics, and protected peptide fragments. The "volatilizable"
      silica-based solid supports and linkers used to illustrate this concept were
      found to be completely removed by their decomposition and ultimate
      "volatilization" during the final cleavage step of synthetic process to yield
      solely the desired synthetic product(s) in the final reaction vessel.

PMID- 15954750
TI  - Generation of N-heterocyclic carbenes by metal-mediated coupling of
      propargylamine and isocyanides.
AB  - A new method for the synthesis of heterocyclic carbenes of imidazol-2-ylidene and
      oxazol-2-ylidene types implying a cycloaddition reaction of propargylamine and
      propargylic alcohol, respectively, to coordinated isocyanide ligands has been
      developed.

PMID- 15954752
TI  - A basket tetradecavanadate cluster with blue luminescence.
AB  - A blue luminescent tetradecavanadate compound, [Et4N]5[V14O36Cl], has been
      synthesized. It possesses an unprecedented half-open basket framework. Through
      the {ABAB}-type stacking, the {V14O36} clusters form infinite one-dimensional
      channels with considerable accessible volume in the crystalline state.

PMID- 15954751
TI  - Template-synthesized DNA nanotubes.
AB  - There is considerable interest in DNA-functionalized nanotubes with proposed
      applications that include use as gene delivery vehicles, in DNA-assisted
      separation and assembly of carbon nanotubes, and in nanotube-based DNA sensing
      and separations. In all of these previous cases, the DNA molecules were attached
      to a nanotube composed of a second material, typically carbon; however, it might
      also be advantageous to have nanotubes composed entirely, or predominately, of
      DNA itself. We describe here a template synthesis method for preparing such DNA
      nanotubes. The synthetic strategy builds on prior work, where we used Mallouk's
      layer-by-layer alpha,omega-diorganophosphonate (alpha,omega-DOP) Zr(IV) chemistry
      to deposit layered alpha,omega-DOP/Zr(IV) nanotubes along the pore walls of an
      alumina template membrane. The DNA nanotubes described here have an outer skin of
      one or more of these alpha,omega-DOP/Zr(IV) layers, to provide structural
      integrity, surrounding an inner core of multiple double-stranded DNA layers held
      together by hybridization between the layers. The DNA molecules comprising these
      nanotubes can be varied at will, and the DNA can be released from the nanotube by
      melting of the DNA duplexes comprising the nanotubes.

PMID- 15954753
TI  - Observation of an Fe(II) spin-crossover in a cesium iron hexacyanochromate.
AB  - In this work, we observed a spin-crossover phenomenon in a cesium iron
      hexacyanochromate, which is a Prussian blue analogue. This compound showed a
      thermal phase transition with transition temperatures of 211 K (T1/2 downward
      arrow) and 238 K (T1/2 upward arrow) due to a spin-crossover on FeII sites. This
      spin-crossover phase transition is accompanied by a lattice contraction of 0.38
      A, but maintains a face-centered cubic structure (F3m). This is the first
      observation of FeII spin-crossover in a series of Prussian blue analogues.

PMID- 15954754
TI  - Unique toroidal morphology from composition and sequence control of triblock
      copolymers.
AB  - The mechanism by which the unique toroidal supramolecular assemblies were formed
      for triblock copolymers of acrylic acid (AA), methyl acrylate (MA), and styrene
      (S), PAA99-b-PMA73-b-PS66, was probed in this study by investigating the
      influences of the block copolymer compositions and sequences. Two triblock
      copolymers, PAA99-b-PMA73-b-PS66 and PAA99-b-PS76-b-PMA62, and two diblock
      copolymers, PAA99-b-PMA155 and PAA99-b-PS133, were studied under experimental
      solution-state conditions that involved a range of solvent/nonsolvent
      (tetrahydrofuran/water) compositions, each in the presence of 2,2'
      (ethylenedioxy)bis(ethylamine). The resulting morphologies were determined by
      transmission electron microscopy. The failures to afford toroidal supramolecular
      assemblies from both diblock copolymers having comparable lengths of the total
      hydrophobic chain segment, either entirely PMA or entirely PS, and from the
      triblock copolymer having a reversed connection sequence for the hydrophobic (PMA
      and PS) segments demonstrate the unique self-assembly behaviors of triblock
      copolymers and the importance of the block copolymer sequence.

PMID- 15954755
TI  - Electrostatic control of aromatic stacking interactions.
AB  - A supramolecular approach has been used to investigate the free energies of
      intermolecular aromatic stacking interactions. Chemical double mutant cycles have
      been used to measure the effect of a range of substituents on face-to-face
      stacking interactions with phenyl and pentafluorophenyl rings. Electrostatic
      effects dominate the trends in interaction energy.

PMID- 15954756
TI  - Ion transfer at nanointerfaces between water and neat organic solvents.
AB  - Nanopipet voltammetry was used for the first study of ion transfer (IT) reactions
      between aqueous solutions and neat organic solvents. An extremely wide (
      approximately 10 V) polarization window obtained with no electrolyte added to the
      organic phase allows one to probe charge transfer reactions, which are not
      normally accessible by electrochemical techniques, for example, the transfer of l
      alaninamide cation from water to 1,2-dichloroethane (DCE). While anions (e.g.,
      chloride) and relatively hydrophobic cations (e.g., tetraalkylammonium ions) can
      be transferred from water to less polar neat solvents such as DCE, the transfers
      of strongly hydrated metal cations occur only in the presence of organic
      supporting electrolyte.

PMID- 15954757
TI  - Single molecule visualization of coordination-assembled porphyrin macrocycles
      reinforced with covalent linkings.
AB  - Coordination-assembled porphyrin macrocycles reinforced with covalent bondings
      were deposited on a metal surface by a pulse injection method, and their scanning
      tunneling microscopy (STM) images were recorded under ultrahigh vacuum conditions
      at liquid nitrogen temperature. The decamer ring consisting of 30 porphyrins gave
      clear circular STM images with hollow structure, whereas that without covalent
      linking did not give clear circular images, showing that covalent linking of the
      coordination pairs by ring-closing metathesis reaction was effective to reinforce
      the supramolecular structure on a metal surface. This strategy will be applicable
      to a variety of supramolecular assemblies.

PMID- 15954758
TI  - Chemoselective covalent coupling of oligonucleotide probes to self-assembled
      monolayers.
AB  - A chemoselective route to routinely and rapidly attach oligonucleotide probes to
      well-defined surfaces is presented. Cu(I) tris(benzyltriazolylmethyl)amine
      catalyzed coupling of terminal acetylenes to azides on a self-assembled monolayer
      is used instead of traditional nucleophilic-electrophilic coupling reactions. The
      reaction proceeds well even in the presence of purposely introduced nucleophilic
      and electrophilic impurities. The density of oligonucleotide probes can be
      controlled by controlling the amount of azide functionality. Although most of our
      work was done on gold surfaces, this technique should be readily applicable to
      any surface on which an azide-containing monolayer can be assembled as we have
      preliminarily demonstrated by derivatizing azidotrimethoxysilane-modified glass
      slides with fluorescein-containing oligonucleotides.

PMID- 15954759
TI  - Direct asymmetric Zn-aldol reaction of methyl vinyl ketone and its synthetic
      applications.
AB  - A direct catalytic asymmetric aldol reaction of methyl vinyl ketone is described
      using our dinuclear zinc catalyst. The obtained aldol adduct functions as a
      bifunctional building block by utilization of the vinyl functionality. For
      example, convergent fragment coupling methods have been demonstrated via highly
      diastereoselective cycloaddition of nitrile oxide after reduction into 1,3-diol
      or via cross-metathesis reaction.

PMID- 15954760
TI  - Primary products and mechanistic considerations in alkane metathesis.
AB  - Alkane metathesis, a reaction catalyzed by the silica-supported tantalum hydride
      [(SiO)2Ta-H], 1, which transforms acyclic alkanes into their higher and lower
      homologues, was reported in 1997. New studies conducted in a continuous flow
      reactor in the case of propane indicate that, by varying the contact time,
      hydrogen and olefins are primary products. This crucial observation, as well as
      the known properties of tantalum alkyls to perform alpha-H or beta-H
      eliminations, supports the proposition of a new mechanism involving
      metallacyclobutane intermediates just like in olefin metathesis. The observed
      selectivities for linear and branched Cn+1 and Cn+2 products as well as the
      linear/branched ratio can be well-explained on the basis of the minimization of
      steric interactions between 1,2- or 1,3-substituents in the various
      tantallacyclobutane intermediates or during their formation. Hydrogen plays a
      specific role in the cleavage of metal alkyls to complete the catalytic cycle.

PMID- 15954761
TI  - Conformational change in unsolvated Trp-cage protein probed by fluorescence.
AB  - We report the first direct measurements of the unfolding of a protein, Trp-cage,
      in the gas phase using laser-induced fluorescence of protein ions in a heated
      quadrupole ion trap. The changes in enthalpy and entropy associated with the
      observed conformational change are obtained by fitting a two-state model of
      protein unfolding to the fluorescence intensities plotted versus temperature. The
      enthalpy and entropy changes for the 2+ and 3+ charge states are greater than the
      values measured in solution and depend on charge state.

PMID- 15954762
TI  - Mechanism of benzylsuccinate synthase: stereochemistry of toluene addition to
      fumarate and maleate.
AB  - Benzylsuccinate synthase catalyzes a highly unusual reaction: the addition of
      toluene to fumarate to form (R)-benzylsuccinic acid. The stereochemistry of this
      reaction has been examined using [d3-methyl]toluene and either fumarate or its
      cis stereoisomer, maleate, as the substrates. We demonstrate that when fumarate
      is the cosubstrate, deuterium is transferred from toluene to the C-3 pro-(R)
      position of benzylsuccinate, implying a syn addition of toluene to the double
      bond of fumarate. However, when maleate is the cosubstrate, the addition of
      toluene occurs in an anti fashion, so that deuterium transfer to the C-3 pro-(R)
      position of benzylsuccinate is also observed. This is consistent with the
      formation of the C-3 radical of benzylsuccinate as an intermediate, in which
      rotation about the C-2-C-3 bond can occur to relieve the sterically unfavorable
      cis conformation of the carboxylate groups when maleate is the cosubstrate.

PMID- 15954763
TI  - Double-cuvette ISES: in situ estimation of enantioselectivity and relative rate
      for catalyst screening.
AB  - Described is a new method for the screening of an array of catalysts, in situ, to
      estimate enantioselectivity and relative rates. We term this approach "double
      cuvette ISES (in situ enzymatic screening)". The Co(III)-salen mediated
      hydrolytic kinetic resolution (HKR) of (+/-)-propylene oxide is used as a model
      reaction to demonstrate proof of principle. In two parallel cuvettes, a lower
      CHCl3-based organic layer is loaded with the epoxide and the chiral salen
      catalyst. Aqueous reporting layers, containing distinct "reporting enzymes" and
      their nicotinamide cofactors, are layered above the organic layers. The 1,2
      propanediol enantiomers formed by the chiral catalyst diffuse into the aqueous
      layer and are oxidized there by the reporting enzymes at rates dependent upon the
      diol concentration, the R:S ratio of the diol, and the enantioselectivity of the
      reporting enzymes. A focused chiral salen library was constructed from seven
      chiral 1,2-diamines, derived from amino acid, terpenoid, and carbohydrates
      skeletons, and seven salicylaldehyde derivatives. Double-cuvette ISES identified
      a couple of interesting combinatorial hits in this salen array, wherein either
      the sense or magnitude of enantioselection for a given chiral diamine depends
      significantly upon the choice of "salicylaldehyde" partner. A comparison of
      predicted ee's and relative rates using this new screening tool with those
      independently measured is provided.

PMID- 15954764
TI  - Design, synthesis, and reactivity of 1-hydrazinodienes for use in organic
      synthesis.
AB  - A new 1-hydrazinodiene (1) has been developed and utilized in Lewis acid
      catalyzed, intermolecular Diels-Alder reactions with various electron-deficient
      alkenes. The hydrazine can then be deprotected, and a molecule of methanesulfinic
      acid is eliminated to provide a putative diazene intermediate (4), which then
      spontaneously undergoes a suprafacial 1,5-sigmatropic shift to yield
      stereochemically complex cyclohexenes. This method has been applied to the
      synthesis of a constitutionally and stereochemically complex decalin derivative.

PMID- 15954765
TI  - n-Type field-effect transistors made of an individual nitrogen-doped multiwalled
      carbon nanotube.
AB  - We report on the fabrication and characterization of field-effect transistor
      based on an individual multiwalled nitrogen-doped carbon nanotube. Our
      measurements show that the N-doped carbon nanotubes have n-type properties. The
      contact properties of the tube and Pt electrodes are also studied in detail.
      Temperature dependence of two-terminal transport experiments suggests that
      transport is dominated by thermionic emission and tunneling through a 0.2 eV
      Schottky contact barrier.

PMID- 15954766
TI  - Protein structure determination by high-resolution solid-state NMR spectroscopy:
      application to microcrystalline ubiquitin.
AB  - High-resolution solid-state NMR spectroscopy has become a promising method for
      the determination of three-dimensional protein structures for systems which are
      difficult to crystallize or exhibit low solubility. Here we describe the
      structure determination of microcrystalline ubiquitin using 2D (13)C-(13)C
      correlation spectroscopy under magic angle spinning conditions. High-resolution
      (13)C spectra have been acquired from hydrated microcrystals of site-directed
      (13)C-enriched ubiquitin. Inter-residue carbon-carbon distance constraints
      defining the global protein structure have been evaluated from 'dipolar-assisted
      rotational resonance' experiments recorded at various mixing times. Additional
      constraints on the backbone torsion angles have been derived from chemical shift
      analysis. Using both distance and dihedral angle constraints, the structure of
      microcrystalline ubiquitin has been refined to a root-mean-square deviation of
      about 1 A. The structure determination strategies for solid samples described
      herein are likely to be generally applicable to many proteins that cannot be
      studied by X-ray crystallography or solution NMR spectroscopy.

PMID- 15954767
TI  - Heats of formation of xenon fluorides and the fluxionality of XeF(6) from high
      level electronic structure calculations.
AB  - Atomization energies at 0 K and heats of formation at 0 and 298 K are predicted
      for XeF(+), XeF(-), XeF(2), XeF(4), XeF(5)(-), and XeF(6) from coupled cluster
      theory (CCSD(T)) calculations with new correlation-consistent basis sets for Xe.
      To achieve near chemical accuracy (+/-1 kcal/mol), up to four corrections were
      added to the complete basis set binding energies based on frozen core coupled
      cluster theory energies: a correction for core-valence effects, a correction for
      scalar relativistic effects, a correction for first-order atomic spin-orbit
      effects, and in some cases, a second-order spin-orbit correction. Vibrational
      zero-point energies were computed at the coupled cluster level of theory. The
      structure of XeF(6) is difficult to obtain with the C(3)(v)() and O(h)()
      structures having essentially the same energy. The O(h)() structure is only 0.19
      kcal/mol below the C(3)(v)() one at the CCSD(T)/CBS level using an approximate
      geometry for the C(3)(v)() structure. With an optimized C(3)(v)() geometry, the
      C(3)(v)() structure would probably become slightly lower in energy than the
      O(h)() one. The calculated heats of formation for the neutral XeF(n)() fluorides
      are less negative than the experimental values from the equilibrium measurements
      by 2.0, 7.7, and 12.2 kcal/mol for n = 2, 4, and 6, respectively. For the
      experimental values, derived from the photoionization measurements, this
      discrepancy becomes even larger, suggesting a need for a redetermination of the
      experimental values. Evidence is presented for the fluxionality of XeF(6) caused
      by the presence of a sterically active, free valence electron pair on Xe.

PMID- 15954768
TI  - A study of the mechanism and kinetics of cyclooctene epoxidation catalyzed by
      iron(III) tetrakispentafluorophenyl porphyrin.
AB  - A study has been conducted of the mechanism and kinetics of cyclooctene
      epoxidation by hydrogen peroxide catalyzed by iron(III) tetrakispentafluorophenyl
      [F(20)TPPFe(III)] porphyrin. The formation of cyclooctene oxide, the only
      product, was determined by gas chromatography, and the consumption of hydrogen
      peroxide was determined by (1)H NMR. UV-visible spectroscopy was used to identify
      the state of the porphyrin as a function of solvent composition and reaction
      conditions and to follow the kinetics of porphyrin degradation. F(20)TPPFe(III)
      was found to be inactive in the chloride-ligated form, but became active when the
      chloride ligand was replaced by a methoxide ligand. The methoxide-ligated form of
      F(20)TPPFe(III) reacts with hydrogen peroxide to form an iron(III) hydroperoxide
      species, which then undergoes both heterolytic and homolytic cleavage to form
      iron(IV) pi-radical cations and iron(IV) oxo species, respectively. The iron(IV)
      pi-radical cations are responsible for the epoxidation of cyclooctene, whereas
      the iron(IV) oxo species are responsible for hydrogen peroxide decomposition. The
      kinetics of cyclooctene epoxidation and hydrogen peroxide decomposition developed
      from the proposed mechanism describe the experimentally observed kinetics
      accurately. The rate parameters derived from a fit of the model to the
      experimental data are consistent with previous estimates of the magnitude of
      these parameters.

PMID- 15954769
TI  - Selective synthesis of 5- or 6-aryl octahydrocyclopenta[b]pyrroles from a common
      precursor through control of competing pathways in a Pd-catalyzed reaction.
AB  - The Pd/phosphine-catalyzed reaction of 1 with aryl bromides leads to the
      selective synthesis of either 6-aryl octahydrocyclopenta[b]pyrroles (3), the
      corresponding 5-aryl isomers 5, diarylamine 2, or hexahydrocyclopenta[b]pyrrole 4
      depending on the structure of the phosphine ligand. These transformations are
      effective with a variety of different aryl bromides and provide 3-5 with
      excellent levels of diastereoselectivity (dr > or = 20:1). The changes in product
      distribution are believed to derive from the influence of Pd-catalyst structure
      on the relative rates of reductive elimination, beta-hydride elimination, alkene
      insertion, and alkene displacement processes in a mechanistically complex
      reaction. The effect of phosphine ligand structure on product distribution is
      described in detail, along with analysis of a proposed mechanism for these
      transformations.

PMID- 15954770
TI  - An efficient unnatural base pair for a base-pair-expanded transcription system.
AB  - For the site-specific incorporation of artificial components into RNA by
      transcription, an efficient, unnatural base pair between 2-amino-6-(2
      thiazolyl)purine (denoted as v) and 2-oxo(1H)pyridine (denoted as y) was
      developed. The substrates of y and 5-substituted y were site-specifically
      incorporated into RNA by T7 RNA polymerase opposite v in templates. The
      efficiency and fidelity of the v-y pairing in transcription were as high as those
      of the natural A-T(U) and G-C pairings. Furthermore, RNAs containing two adjacent
      y bases were also transcribed from DNA templates containing two v bases. This
      specific transcription allows the large-scale preparation of artificial RNAs and
      can be combined with other systems to simultaneously incorporate several
      different components into a transcript.

PMID- 15954771
TI  - High purity anatase TiO(2) nanocrystals: near room-temperature synthesis, grain
      growth kinetics, and surface hydration chemistry.
AB  - High purity, spherical anatase nanocrystals were prepared by a modified sol-gel
      method. Mixing of anhydrous TiCl(4) with ethanol at about 0 degrees C yielded a
      yellowish sol that was transformed into phase-pure anatase of 7.7 nm in size
      after baking at 87 degrees C for 3 days. This synthesis route eliminates the
      presence of fine seeds of the nanoscale brookite phase that frequently occurs in
      low-temperature formation reactions and also significantly retards the phase
      transformation to rutile at high temperatures. Heating the as-is 7.7 nm anatase
      for 2 h at temperatures up to 600 degrees C leads to an increase in grain size of
      the anatase nanoparticles to 32 nm. By varying the calcination time from 2 to 48
      h at 300 degrees C, the particle size could be controlled between 12 and 15.3 nm.
      The grain growth kinetics of anatase nanoparticles was found to follow the
      equation, D(2) - D(0)(2) = k(0)t(m)e((-)(E)(a)/(RT)) with a time exponent m =
      0.286(+/-9) and an activation energy of E(a) = 32 +/- 2 kJ x mol(-)(1).
      Thermogravimetric analysis in combination with infrared and X-ray photoemission
      spectroscopies has shown the anatase nanocrystals at different sizes to be
      composed of an interior anatase lattice with surfaces that are hydrogen-bonded to
      a wide set of energetically nonequivalent groups. With a decrease in particle
      size, the anatase lattice volume contracts, while the surface hydration
      increases. The removal of the surface hydration layers causes coarsening of the
      nanoparticles.

PMID- 15954772
TI  - Mechanistic insights in charge-transfer-induced luminescence of 1,2-dioxetanones
      with a substituent of low oxidation potential.
AB  - We have investigated the decomposition pathway of dioxetanones 1c with a
      phenoxide anion group by the B3LYP/6-31+G(d) method together with the second
      order multireference Moller-Plesset perturbation (MRMP) theory and propose charge
      transfer-induced luminescence (CTIL) with polarization-induced branching
      excitation processes. In the gas phase, the thermal decomposition of 1c occurs by
      an asynchronous two-stage pathway without a discrete intermediate; that is, the
      initial O-O bond breaking to generate a charge-transfer (CT) diradical species is
      immediately followed by the subsequent C-C bond breaking with simultaneous back
      CT, which is responsible for the surface crossing at the avoided crossing. The
      activation energy is dramatically reduced from 19.4 to 3.8 kcal mol(-)(1) by the
      deprotonation of phenol meta-1d to its anion meta-1c, showing an important role
      of the endothermic CT. The odd/even selection rule for the chemiluminescence
      efficiency can be explained by the orbital interaction for the back CT between
      the carbonyl pi orbital and either a HOMO or a LUMO of the generated light
      emitters. To examine the accessibility of the chemically initiated electron
      exchange luminescence (CIEEL) route, we considered the solvent effects on the
      free-energy change of meta-1c by using continuum solvent models. The bending
      vibration mode of the CO(2) fragment is specifically considered. Borderline
      features emerges from the solution-phase CT reaction of meta-1c, which depends on
      the solvent polarity: one is a nonadiabatic or adiabatic back CT process
      (polarization-induced concerted CTIL), and the other is a radical dissociation,
      i.e., complete one-electron-transfer process (CIEEL).

PMID- 15954773
TI  - Neutral structures with a planar tetracoordinated carbon based on spiropentadiene
      analogues.
AB  - Neutral hydrocarbon structures containing a planar tetracoordinated carbon atom
      are proposed on the basis of quantum chemical calculations. The planarity at the
      central carbon atom is achieved by using aromaticity for stabilizing a positively
      charged core moiety that contains the planar atom. This charge is compensated by
      negatively charged cyclopentadienyl rings fused on the structure, leading to
      neutral structures. These are found to be stable from a dynamic point of view and
      are potentially synthesizable through carbene chemistry. These structures can
      lead to new breakthroughs in the chemical structure theory. A family of species
      derived from this model is also presented.

PMID- 15954774
TI  - Synthesis and identification of small molecules that potently induce apoptosis in
      melanoma cells through G1 cell cycle arrest.
AB  - Late-stage malignant melanoma is a cancer that is refractory to current
      chemotherapeutic treatments. The average survival time for patients with such a
      diagnosis is 6 months. In general, the vast majority of anticancer drugs operate
      through induction of cell cycle arrest and cell death in either the DNA synthesis
      (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms
      that melanocytes possess to protect cells from DNA damage often confer resistance
      to drugs that derive their toxicity from S or M phase arrest. Described herein is
      the synthesis of a combinatorial library of potential proapoptotic agents and the
      subsequent identification of a class of small molecules (triphenylmethylamides,
      TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell
      cycle. Several of these TPMAs are quite potent inducers of apoptotic death in
      melanoma cell lines (IC(50) approximately 0.5 muM), and importantly, some TPMAs
      are comparatively nontoxic to normal cells isolated from the bone marrow of
      healthy donors. Furthermore, the TPMAs were found to dramatically reduce the
      level of active nuclear factor kappa-B (NFkappaB) in the cell; NFkappaB is known
      to be constitutively active in melanoma, and this activity is critical for the
      proliferation of melanoma cells and their evasion of apoptosis. Compounds that
      reduce the level of NFkappaB and arrest cells in the G1 phase of the cell cycle
      can provide insights into the biology of melanoma and may be effective
      antimelanoma agents.

PMID- 15954775
TI  - Structures and displacement of 1-adamantanethiol self-assembled monolayers on
      Au{111}.
AB  - We have designed monolayers with weak intermolecular interactions for use as
      placeholders in intelligent self- and directed-assembly. We have shown that these
      1-adamantanethiolate monolayers are labile with respect to displacement by
      exposing them to dilute solutions of alkanethiols. These self-assembled
      monolayers (SAMs) of 1-adamantanethiol on Au{111} were probed using ambient
      scanning tunneling microscopy (STM), and their assembled order was determined.
      Solution deposition of the molecules results in a highly ordered hexagonally
      close-packed molecular lattice with a measured nearest neighbor distance of 6.9
      +/- 0.4 A. The SAMs exhibit several rotational domains, but lack the protruding
      domain boundaries typical of alkanethiolate SAMs, and are similarly stable at
      room temperature. Co-deposition of alkanethiol and 1-adamantanethiol from
      solution results in alkanethiolate SAMs, except when using extremely low
      alkanethiol to 1-adamantanethiol concentration ratios. Facile displacement of low
      interaction strength SAMs can be exploited to enhance patterning using soft
      nanolithography.

PMID- 15954776
TI  - Protein boson peak originated from hydration-related multiple minima energy
      landscape.
AB  - The boson peak is a broad peak found in the low-frequency region of inelastic
      neutron and Raman scattering spectra in many glassy materials, including
      biopolymers below approximately 200 K. Here, we give a novel insight into the
      origins of the protein boson peak, which may also be valid for materials other
      than proteins. Molecular simulation reveals that the structured water molecules
      around a protein molecule increase the number of local minima in the protein
      energy landscape, which plays a key role in the origin of the boson peak. The
      peak appears when the protein dynamics are trapped within a local energy minimum
      at cryogenic temperatures. This trapping causes very low frequency collective
      motions to shift to higher frequencies. We demonstrate that the characteristic
      frequency of such systems shifts higher as the temperature decreases also in
      model one-dimensional energy surfaces with multiple minima.

PMID- 15954777
TI  - Spectroscopic and computational studies of the ATP:corrinoid adenosyltransferase
      (CobA) from Salmonella enterica: insights into the mechanism of adenosylcobalamin
      biosynthesis.
AB  - CobA from Salmonella enterica is a member of an enzymatic system responsible for
      the de novo biosynthesis of adenosylcobalamin (AdoCbl), catalyzing the formation
      of the essential Co-C bond by transferring the adenosyl group from a molecule of
      ATP to a transient Co(1+)corrinoid species generated in the enzyme active site. A
      particularly fascinating aspect of this reaction is that the flavodoxin in vivo
      reducing agent that serves as the electron donor to CobA possesses a reduction
      potential that is considerably more positive than that of the Co(2+/1+) couple of
      the corrinoid substrate. To explore how CobA may overcome this challenge, we have
      employed electronic absorption, magnetic circular dichroism, and electron
      paramagnetic resonance (EPR) spectroscopies to probe the interaction between
      Co(3+)- and Co(2+)corrinoids and the enzyme active site. Our data reveal that
      while Co(3+)corrinoids interact only weakly with CobA, Co(2+)corrinoids undergo
      partial conversion to a new paramagnetic species that can be obtained in nearly
      quantitative yield when CobA is preincubated with the co-substrate ATP. This
      "activated" species is characterized by a distinct set of ligand field
      transitions in the near-IR spectral region and EPR parameters that are
      unprecedented for Co(2+)corrinoids. Analysis of these data on the basis of
      qualitative spectral correlations and density functional theory computations
      reveals that this unique Co(2+)corrinoid species possesses an essentially square
      planar Co(2+) center that lacks any significant axial bonding interactions.
      Possible implications of these findings for the mechanism of Co(2+) --> Co(1+)
      reduction employed by CobA and Co-C bond-forming enzymes in general are explored.

PMID- 15954778
TI  - Immobilization of rhodium complexes at thiolate monolayers on gold surfaces:
      catalytic and structural studies.
AB  - Chiral rhodium-diphosphine complexes have been incorporated into self-assembled
      thiolate monolayers (SAMs) on gold colloids. Catalysts of this type are of
      interest because they combine properties of homogeneous and heterogeneous
      systems. In addition, it should be possible to influence the catalytic properties
      of the metal center by the neighboring thiolate molecules. Colloids with a
      diameter of ca. 3 nm, coated with a mixed monolayer of n-octanethiolates and
      thiolates with chiral rhodium-PYRPHOS end groups, were studied as hydrogenation
      catalysts. With methyl alpha-acetamido-cinnamate as substrate, virtually the same
      enantioselectivities (up to 93% ee) and full conversion were obtained as with the
      corresponding homogeneous [Rh(COD)(PYRPHOS)]BAr(F) catalyst. The colloids were
      easily recovered by filtration and reused as catalysts three times without loss
      of enantioselectivity. STM studies of analogous SAMs on Au(111) gave a detailed
      picture of the structure and dynamics of mixed monolayers of this type. The STM
      images showed that the catalyst-bearing thiolates are distributed statistically
      on the surface and that the ordered structure of the n-octanethiolate SAM can be
      retained during incorporation of the catalyst-bearing thiols using the place
      exchange methodology.

PMID- 15954779
TI  - Crystal structures, electronic properties, and pressure-induced superconductivity
      of the tetrahedral cluster compounds GaNb(4)S(8), GaNb(4)Se(8), and GaTa(4)Se(8).
AB  - The crystal structures of the tetrahedral cluster compounds GaNb(4)S(8) and
      GaTa(4)Se(8) were determined by single-crystal X-ray diffraction. They
      crystallize in the cubic GaMo(4)S(8) structure type (F3m), which can be derived
      from the spinel type by shifting the metal atoms off the centers of the chalcogen
      octahedra along [111]. Electrical resistivity and magnetic susceptibility
      measurements show that the electronic conduction originates from hopping of
      localized unpaired electrons (S = (1)/(2)) among widely separated Nb(4) or Ta(4)
      clusters, and thus these materials represent a new class of Mott insulators.
      Under high pressure we find that GaNb(4)S(8) undergoes a transition from the Mott
      insulating to a superconducting state with T(C) up to 4 K at 23 GPa, similar to
      GaNb(4)Se(8) and GaTa(4)Se(8). High-pressure single-crystal X-ray studies of
      GaTa(4)Se(8) reveal that the superconducting transition is connected with a
      gradual decrease of the octahedral distortion with increasing pressure. DFT band
      structure calculations show that weakly coupled cluster orbitals are responsible
      for a high density of states at the Fermi level. The correct insulating magnetic
      ground state for GaNb(4)S(8) with mu(eff) = 1.73 mu(B) is for the first time
      achieved by the LDA+U method using U = 6 eV and rhombohedral symmetry.

PMID- 15954780
TI  - Polymorphism in AB(13) nanoparticle superlattices: an example of semiconductor
      metal metamaterials.
AB  - Colloidal crystallization of nanoparticles with different functionalities into
      multicomponent assemblies provides a route to new classes of ordered
      nanocomposites with novel properties tunable by the choice of the constituent
      building blocks. While theories based on hard sphere approximation predict
      crystallization of only a few stable binary phases (NaCl-, AlB(2)- and NaZn(13)
      type), we find that additional polymorphs of lower packing density are possible.
      We demonstrate that PbSe and Pd nanoparticles can be reproducibly crystallized
      into two polymorphs with AB(13) stoichiometry. One polymorph is isostructural
      with the intermetallic compound NaZn(13) and is consistent with dense packing of
      hard spheres driven by entropy. The second unanticipated polymorph is of lower
      packing density. This observation underscores the shortcomings of applying simple
      space-filling principles to the crystallization of organically passivated
      nanocrystals and further motivates the development of models that incorporate
      combinations of hard-sphere, van der Waals, dipolar, and hydrophobic forces. This
      work demonstrates that ordered periodic structures with lower packing density are
      achievable and provides the first example of a binary semiconductor-metal
      superlattice using a combination of PbSe-Pd nanocrystals.

PMID- 15954781
TI  - Understanding the template preorganization step of an artificial arginine
      receptor.
AB  - A biomimetic complex which mimics the arginine-phosphonate diester interaction of
      the arginine fork is investigated with respect to structure and energetics of
      stable configurations. Within this work, we provide knowledge on local minima of
      the isolated system obtained from first-principles calculations. Non-negligible
      solvation effects are studied in a microsolvation approach. The interactions
      which govern the structural patterns of molecular recognition in this tweezer
      guest complex can be significantly modulated by the action of hydrogen bond
      accepting and donating solvent molecules, such as dimethyl sulfoxide or water,
      which were present in experimental investigations on this system. Different
      tweezer-guest structures are evaluated with respect to their temperature
      dependent thermodynamical properties as products of the first association
      reaction step of the bisphosphonate tweezer template and the guanidinium moiety.

PMID- 15954782
TI  - Bilayers and interdigitation in block copolymer vesicles.
AB  - Amphiphilic block copolyethers assemble into membranes with thickness between 2.4
      and 7.5 nm. The vesicular morphology has been confirmed by small-angle X-ray
      scattering combined with electron microscopy for diblock copolymers and triblock
      copolymers of both architectures. The scaling of the membrane thicknesses with
      the length of the hydrophobic block is in good agreement with the strong
      segregation theory for block copolymer melts, indicating a mixed and stretched
      conformation of the hydrophobic chain inside the vesicle membrane. This result is
      in contrast to previously published results where the hydrophobic membranes were
      observed to have bilayer geometry and polymer chains that are relatively
      unperturbed from their ideal Gaussian dimensions.

PMID- 15954783
TI  - Theoretical analysis of factors controlling the nonalternating CO/C(2)H(4)
      copolymerization.
AB  - A [P-O]Pd catalyst based on o-alkoxy derivatives of diphenylphosphinobenzene
      sulfonic acid (I) has recently been shown by Drent et al. to perform
      nonalternating CO/C(2)H(4) copolymerization with subsequent incorporation of
      ethylene units into the polyketone chain. The origin of the nonalternation is
      investigated in a theoretical study of I, where calculated activation barriers
      and reaction heats of all involved elementary steps are used to generate a
      complete kinetic model. The kinetic model is able to account for the observed
      productivity and degree of nonalternation as a function of temperature.
      Consistent with the energy changes obtained for the real catalyst model, the
      selectivity toward a nonalternating distribution of both comonomers appears to be
      mainly a result of a strong destabilization of the Pd-acyl complex.

PMID- 15954784
TI  - Fluorescence correlation spectroscopy, a tool to investigate supramolecular
      dynamics: inclusion complexes of pyronines with cyclodextrin.
AB  - The control of supramolecular systems requires a thorough understanding of their
      dynamics on a molecular level. We present fluorescence correlation spectroscopy
      (FCS) as a powerful spectroscopic tool to study supramolecular dynamics with
      single molecule sensitivity. The formation of a supramolecular complex between
      beta-cyclodextrin (beta-CD) as host and pyronines Y (PY) and B (PB) as guests is
      studied by FCS. Global target analysis of full correlation curves with a newly
      derived theoretical model yields in a single experiment the fluorescence
      lifetimes and the diffusion coefficients of free and complexed guests and the
      rate constants describing the complexation dynamics. These data give insight into
      the recently published surprising fact that the association equilibrium constant
      of beta-CD with PY is much lower than that with the much bulkier guest PB. FCS
      shows that the stability of the complexes is dictated by the dissociation and not
      by the association process. The association rate constants are very similar for
      both guests and among the highest reported for this type of systems, although
      much lower than the diffusion-controlled collision rate constant. A two-step
      model including the formation of an encounter complex allows one to identify the
      unimolecular inclusion reaction as the rate-limiting step. Simulations indicate
      that this step may be controlled by geometrical and orientational requirements.
      These depend on critical molecular dimensions which are only weakly affected by
      the different alkyl substituents of PY and PB. Diffusion coefficients of PY and
      PB, of their complexes, and of rhodamine 110 are given and compared to those of
      similar molecules.

PMID- 15954785
TI  - (4,2)D Projection--reconstruction experiments for protein backbone assignment:
      application to human carbonic anhydrase II and calbindin D(28K).
AB  - Projection-reconstruction NMR experiments have been shown to significantly reduce
      the acquisition time required to obtain protein backbone assignment data. To
      date, this concept has only been applied to smaller (15)N/(13)C-labeled proteins.
      Here, we show that projection-reconstruction NMR techniques can be extended to
      larger protonated and perdeuterated proteins. We present a suite of (4,2)D triple
      resonance experiments for protein backbone assignment and a Hybrid
      Backprojection/Lower-Value algorithm for reconstructing data with relatively weak
      signal-to-noise ratios. In addition, we propose a sampling theorem and discuss
      its implication on the choice of projection angles. We demonstrate the efficacy
      of this approach using the 29 kDa protein, human carbonic anhydrase II and the 30
      kDa protein, calbindin D(28K).

PMID- 15954786
TI  - CdO as the archetypical transparent conducting oxide. Systematics of dopant ionic
      radius and electronic structure effects on charge transport and band structure.
AB  - A series of yttrium-doped CdO (CYO) thin films have been grown on both amorphous
      glass and single-crystal MgO(100) substrates at 410 degrees C by metal-organic
      chemical vapor deposition (MOCVD), and their phase structure, microstructure,
      electrical, and optical properties have been investigated. XRD data reveal that
      all as-deposited CYO thin films are phase-pure and polycrystalline, with features
      assignable to a cubic CdO-type crystal structure. Epitaxial films grown on single
      crystal MgO(100) exhibit biaxial, highly textured microstructures. These as
      deposited CYO thin films exhibit excellent optical transparency, with an average
      transmittance of >80% in the visible range. Y doping widens the optical band gap
      from 2.86 to 3.27 eV via a Burstein-Moss shift. Room temperature thin film
      conductivities of 8,540 and 17,800 S/cm on glass and MgO(100), respectively, are
      obtained at an optimum Y doping level of 1.2-1.3%. Finally, electronic band
      structure calculations are carried out to systematically compare the structural,
      electronic, and optical properties of the In-, Sc-, and Y-doped CdO systems. Both
      experimental and theoretical results reveal that dopant ionic radius and
      electronic structure have a significant influence on the CdO-based TCO crystal
      and band structure: (1) lattice parameters contract as a function of dopant ionic
      radii in the order Y (1.09 A) < In (0.94 A) < Sc (0.89 A); (2) the carrier
      mobilities and doping efficiencies decrease in the order In > Y > Sc; (3) the
      dopant d state has substantial influence on the position and width of the s-based
      conduction band, which ultimately determines the intrinsic charge transport
      characteristics.

PMID- 15954787
TI  - Three-dimensional structure of nanocomposites from atomic pair distribution
      function analysis: study of polyaniline and (polyaniline)(0.5)V(2)O(5) x 1.0
      H(2)O.
AB  - The three-dimensional structures of emeraldine base polyaniline (PANI) and
      (polyaniline)(0.5)V(2)O(5) x 1.0 H(2)O have been determined by total X-ray
      scattering experiments. Atomic pair distribution functions (PDF) were measured to
      obtain experimental observables against which structural models were tested and
      refined. The PDF approach is necessary because of the limited structural
      coherence in these nanostructured materials. Polyaniline possesses a well-defined
      local atomic arrangement that can be described in terms of an 84-atom
      orthorhombic unit cell. The nanocomposite (PANI)(0.5)V(2)O(5) x 1.0 H(2)O too is
      locally well ordered and may be described in terms of a small number of structure
      sensible parameters. The PDF approach allows the construction of structure models
      of PANI and (PANI)(0.5)V(2)O(5) x 1.0 H(2)O on the basis of which important
      materials' properties can be explained predicted and possibly improved.

PMID- 15954788
TI  - A chemical sensor for the liquid-ordered phase.
AB  - The mixing properties of exchangeable phospholipids, derived from 1,2-dipalmitoyl
      sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3
      phosphoethanolamine, with an exchangeable form of cholesterol have been used to
      monitor the transition from the liquid-disordered to the liquid-ordered phase in
      cholesterol-containing bilayers, made from 1,2-dipalmitoyl-sn-glycero-3
      phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphocholine, respectively.

PMID- 15954789
TI  - Combined ruthenium(II) and lipase catalysis for efficient dynamic kinetic
      resolution of secondary alcohols. Insight into the racemization mechanism.
AB  - Pentaphenylcyclopentadienyl ruthenium complexes (3) are excellent catalysts for
      the racemization of secondary alcohols at ambient temperature. The combination of
      this process with enzymatic resolution of the alcohols results in a highly
      efficient synthesis of enantiomerically pure acetates at room temperature with
      short reaction times for most substrates. This new reaction was applied to a wide
      range of functionalized alcohols including heteroaromatic alcohols, and for many
      of the latter, enantiopure acetates were efficiently prepared for the first time
      via dynamic kinetic resolution (DKR). Different substituted cyclopentadienyl
      ruthenium complexes were prepared and studied as catalysts for racemization of
      alcohols. Pentaaryl-substituted cyclopentadienyl complexes were found to be
      highly efficient catalysts for the racemization. Substitution of one of the aryl
      groups by an alkyl group considerably slows down the racemization process. A
      study of the racemization of (S)-1-phenylethanol catalyzed by ruthenium hydride
      eta(5)-Ph(5)CpRu(CO)(2)H (8) indicates that the racemization takes place within
      the coordination sphere of the ruthenium catalyst. This conclusion was supported
      by the lack of ketone exchange in the racemization of (S)-1-phenylethanol
      performed in the presence of p-tolyl methyl ketone (1 equiv), which gave <1% of 1
      (p-tolyl)ethanol. The structures of ruthenium chloride and iodide complexes 3a
      and 3c and of ruthenium hydride complex 8 were confirmed by X-ray analysis.

PMID- 15954790
TI  - Enantioselective organocatalytic alpha-fluorination of aldehydes.
AB  - The first direct enantioselective catalytic alpha-fluorination of aldehydes has
      been accomplished. The use of enamine catalysis has provided a new
      organocatalytic strategy for the enantioselective fluorination of aldehydes to
      generate alpha-fluoro aldehydes, an important chiral synthon for medicinal agent
      synthesis. The use of imidazolidinone 1 as the asymmetric catalyst has been found
      to mediate the fluorination of a large variety of aldehyde substrates with N
      fluorobenzenesulfonimide serving as the electrophilic source of fluorine. A
      diverse spectrum of aldehyde substrates can also be accommodated in this new
      organocatalytic transformation. While catalyst quantities of 20 mol % were
      generally employed in this study, successful halogenation can be accomplished
      using catalyst loadings as low as 2.5 mol %.

PMID- 15954791
TI  - Influence of inter- and intramolecular hydrogen bonding on kemp decarboxylations
      from QM/MM simulations.
AB  - The Kemp decarboxylation reaction for benzisoxazole-3-carboxylic acid derivatives
      has been investigated using QM/MM calculations in protic and dipolar aprotic
      solvents. Aprotic solvents have been shown to accelerate the rates of reaction by
      7-8 orders of magnitude over water; however, the inclusion of an internal
      hydrogen bond effectively inhibits the reaction with near solvent independence.
      The effects of solvation and intramolecular hydrogen bonding on the reactants,
      transition structures, and the rate of reaction are elucidated using two
      dimensional potentials of mean force (PMF) derived from free energy perturbation
      calculations in Monte Carlo simulations (MC/FEP). Free energies of activation in
      six solvents have been computed to be in close agreement with experiment. Solute
      solvent interaction energies show that poorer solvation of the reactant anion in
      the dipolar aprotic solvents is primarily responsible for the observed rate
      enhancements over protic media. In addition, a discrepancy for the experimental
      rate in chloroform has been studied in detail with the conclusion that ion
      pairing between the reactant anion and tetramethylguanidinium counterion is
      responsible for the anomalously slow reaction rate. The overall quantitative
      success of the computations supports the present QM/MM/MC approach, which
      features PDDG/PM3 as the QM method.

PMID- 15954792
TI  - Tuning first molecular hyperpolarizabilities through the use of proaromatic
      spacers.
AB  - In this paper, we describe the second-order nonlinear optical properties of a
      series of 1,3-dithiole-based electron donor-acceptor systems incorporating
      proaromatic donor and spacer groups. Modification of the proaromaticity of the
      quinoid spacer gives rise to NLO-phores with mubeta values ranging from -2000 x
      10(-)(48) esu to +3000 x 10(-)(48) esu. Quite surprisingly, compounds with a p
      benzoquinoid spacer and a strong acceptor group show negative mubeta values,
      usually associated to zwitterionic ground states, and yet they are largely
      quinoid, as evidenced by crystallographic data and theoretical calculations.
      Progressive benzoannulation of the spacer and introduction of alkylsulfanyl
      substituents on the dithiole donor unit result in a shift to more positive mubeta
      values. DFT and ab initio calculations verify these empirical trends.

PMID- 15954793
TI  - Synthesis of stable and cell-type selective analogues of cyclic ADP-ribose, a
      Ca(2+)-mobilizing second messenger. Structure--activity relationship of the N1
      ribose moiety.
AB  - We previously developed cyclic ADP-carbocyclic ribose (cADPcR, 2) as a stable
      mimic of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. A
      series of the N1-ribose modified cADPcR analogues, designed as novel stable
      mimics of cADPR, which were the 2"-deoxy analogue 3, the 3"-deoxy analogue 4, the
      3"-deoxy-2"-O-(methoxymethyl) analogue 5, the 3"-O-methyl analogue 6, the 2",3"
      dideoxy analogue 7, and the 2",3"-dideoxydidehydro analogue 8, were successfully
      synthesized using the key intramolecular condensation reaction with
      phenylthiophosphate-type substrates. We investigated the conformations of these
      analogues and of cADPR and found that steric repulsion between both the adenine
      and N9-ribose moieties and between the adenine and N1-ribose moieties was a
      determinant of the conformation. The Ca(2+)-mobilizing effects were evaluated
      systematically using three different biological systems, i.e., sea urchin eggs,
      NG108-15 neuronal cells, and Jurkat T-lymphocytes. The relative potency of Ca(2+)
      mobilization by these cADPR analogues varies depending on the cell-type used:
      e.g., 3"-deoxy-cADPcR (4) > cADPcR (2) > cADPR (1) in sea urchin eggs; cADPR (1)
      >> cADPcR (2) approximately 3"-deoxy-cADPcR (4) in T-cells; and cADPcR (2) >
      cADPR (1) > 3"-deoxy-cADPcR (4) in neuronal cells, respectively. These indicated
      that the target proteins and/or the mechanism of action of cADPR in sea urchin
      eggs, T-cells, and neuronal cells are different. Thus, this study represents an
      entry to cell-type selective cADPR analogues, which can be used as biological
      tools and/or novel drug leads.

PMID- 15954794
TI  - Divergent mechanisms of suicide inactivation for ethanolamine ammonia-lyase.
AB  - Ab initio molecular orbital calculations have been used to study the mechanism of
      suicide inactivation of ethanolamine ammonia-lyase induced by three different
      substrate analogues. Analysis of the normal catalytic mechanism with 2
      aminoethanol (ethanolamine) as substrate predicts that both the hydrogen
      abstraction and hydrogen-reabstraction steps involving the B(12)-cofactor are
      likely to be exothermic. On the other hand, the proposed inactivation mechanism
      for the first substrate analogue, glycolaldehyde, leads to a highly stabilized
      radical that results in a very endothermic (by ca. 90 kJ mol(-)(1)) hydrogen
      reabstraction step, which is thought to halt the normal function of the enzyme.
      Curiously, the energy requirements for a catalytically imposed mechanism in the
      case of the second substrate analogue, 2-hydroxyethylhydrazine (HEH), parallel
      those for the catalytic substrate, despite the fact that HEH is found to
      inactivate EAL experimentally. However, further analysis reveals the presence of
      a lower energy pathway for HEH that leads to the formation of the highly
      stabilized hydrazinium radical cation. In a manner similar to when glycolaldehyde
      is the substrate analogue, this results in an endothermicity for the hydrogen
      reabstraction step that is prohibitively large. In contrast to these related
      inactivation mechanisms, the third substrate analogue, 2-aminoacetaldehyde,
      apparently accomplishes the inactivation of EAL in an entirely different manner.
      A pathway for the experimentally observed formation of acetic acid and ammonium
      cation has been identified and appears catalytic in the sense that 5'
      deoxyadenosyl radical is regenerated. However, mechanisms to account for the
      subsequent formation of 4',5'-anhydroadenosine and degradation of the corrinoid
      ring of the cofactor have not been elucidated.

PMID- 15954795
TI  - Single-step covalent functionalization of polylactide surfaces.
AB  - A single-step, nondestructive, and versatile technique for the grafting and
      chemical surface modification of biodegradable polymers such as polylactide is
      described. The substrates are subjected to the vapor phase of any of three
      investigated vinyl monomers: acrylamide, maleic anhydride, and N
      vinylpyrrolidone, and grafting is induced by photoinitiation of benzophenone
      under solvent free conditions. The modified surfaces exhibit higher wettability,
      and the grafting is verified by X-ray photoelectron spectroscopy, attenuated
      total reflection Fourier-transform IR, contact-angle measurements, and scanning
      electron microscopy. The graft-chain pendant groups remain functional and can
      subsequently be modified so that a tailor-made surface with desired properties
      may be achieved.

PMID- 15954796
TI  - The total synthesis of coleophomones B, C, and D.
AB  - Members of the coleophomone family of natural products all possess several
      intriguing and challenging architectural features, as well as exhibit unusual
      biological activity. They, therefore, constitute attractive targets for
      synthesis. In this Article, we describe the total synthesis of coleophomones B
      (2), C (3), and D (4). The highly strained and congested 11-membered macrocycle
      of coleophomones B (2) and C (3) was constructed using an impressive olefin
      metathesis reaction. Furthermore, both of the requisite geometric isomers of the
      Delta(16,17) within the macrocycle could be accessed from a common precursor,
      facilitating a divergence that lent the coleophomone B (2)/C (3) synthesis an
      unusually high degree of efficiency. The synthesis of coleophomone D (4)
      confirmed that it exists as a dynamic mixture of isomeric forms with a different
      aromatic substitution pattern from the other family members.

PMID- 15954797
TI  - Designed ferromagnetic, ferroelectric Bi(2)NiMnO(6).
AB  - A newly designed ferromagnetic, ferroelectric compound, Bi(2)NiMnO(6), was
      prepared by high-pressure synthesis at 6 GPa. The crystal structure, as
      determined by synchrotron X-ray powder diffraction, is a heavily distorted double
      perovskite with Ni(2+) and Mn(4+) ions ordered in a rock-salt configuration. The
      presence of 6s(2) lone pairs of Bi(3+) ions and the covalent Bi-O bonds give
      ferroelectric properties with T(CE) of 485 K, while -Ni(2+)-O-Mn(4+)-O-Ni(2+)-
      magnetic paths lead to a ferromagnetism with T(CM) of 140 K. This simple material
      design to distribute two magnetic elements with and without e(g) electrons on B
      sites of Bi- and Pb-based perovkites can be applied to other Bi(2)M(2+)M'(4+)O(6)
      and Pb(2)M(3+)M'(5+)O(6) systems to search for newer ferromagnetic
      ferroelectrics.

PMID- 15954798
TI  - Thickness transition of a rigid supramolecular polymer.
AB  - A low molecular weight bisurea in nonpolar solvents is shown to self-assemble by
      hydrogen bonding into two distinct high molecular weight structures. At low
      temperature and high concentration, the most stable structure is a thick
      cylindrical assembly, responsible for the very high viscosity of the solution. At
      higher temperature or lower concentration, the thick filaments disappear in favor
      of thinner filaments, leading to a lower viscosity. The reversible transition
      occurs over a temperature range of 5 degrees C only, showing that it is highly
      cooperative. The structural switch can also be triggered by changing the nature
      of the solvent or the composition in the case of a mixture of two bisureas. The
      high cooperativity and the tunability of this transition are useful for the
      design of responsive materials.

PMID- 15954800
TI  - Self-assembling peptide detergents stabilize isolated photosystem I on a dry
      surface for an extended time.
AB  - We used a class of designed peptide detergents to stabilize photosystem I (PS-I)
      upon extended drying under N2 on a gold-coated-Ni-NTA glass surface. PS-I is a
      chlorophyll-containing membrane protein complex that is the primary reducer of
      ferredoxin and the electron acceptor of plastocyanin. We isolated the complex
      from the thylakoids of spinach chloroplasts using a chemical detergent. The
      chlorophyll molecules associated with the PS-I complex provide an intrinsic
      steady-state emission spectrum between 650 and 800 nm at -196.15 degrees C that
      reflects the organization of the pigment-protein interactions. In the absence of
      detergents, a large blue shift of the fluorescence maxima from approximately 735
      nm to approximately 685 nm indicates a disruption in light-harvesting subunit
      organization, thus revealing chlorophyll-protein interactions. The commonly used
      membrane protein-stabilizing detergents, N-dodecyl-beta-D-maltoside and N-octyl
      beta-D-glucoside, only partially stabilized the approximately 735-nm complex with
      approximately 685-nm spectroscopic shift. However, prior to drying, addition of
      the peptide detergent acetyl-AAAAAAK at increasing concentration significantly
      stabilized the PS-I complex. Moreover, in the presence of acetyl-AAAAAAK, the PS
      I complex is stable in a dried form at room temperature for at least 3 wk.
      Another peptide detergent, acetyl-VVVVVVD, also stabilized the complex but to a
      lesser extent. These observations suggest that the peptide detergents may
      effectively stabilize membrane proteins in the solid-state. These designed
      peptide detergents may facilitate the study of diverse types of membrane
      proteins.

PMID- 15954801
TI  - Rab7 associates with early endosomes to mediate sorting and transport of Semliki
      forest virus to late endosomes.
AB  - Semliki forest virus (SFV) is internalized by clathrin-mediated endocytosis, and
      transported via early endosomes to late endosomes and lysosomes. The
      intracellular pathway taken by individual fluorescently labeled SFV particles was
      followed using immunofluorescence in untransfected cells, and by video-enhanced,
      triple-color fluorescence microscopy in live cells transfected with GFP- and RFP
      tagged Rab5, Rab7, Rab4, and Arf1. The viruses progressed from Rab5-positive
      early endosomes to a population of early endosomes (about 10% of total) that
      contained both Rab5 and Rab7. SFV were sequestered in the Rab7 domains, and they
      were sorted away from the early endosomes when these domains detached as separate
      transport carriers devoid of Rab5, Rab4, EEA1, Arf1, and transferrin. The process
      was independent of Arf1 and the acidic pH in early endosomes. Nocodazole
      treatment showed that the release of transport carriers was assisted by
      microtubules. Expression of constitutively inactive Rab7T22N resulted in
      accumulation of SFV in early endosomes. We concluded that Rab7 is recruited to
      early endosomes, where it forms distinct domains that mediate cargo sorting as
      well as the formation of late-endosome-targeted transport vesicles.

PMID- 15954802
TI  - Precise temporal modulation in the response of the SOS DNA repair network in
      individual bacteria.
AB  - The SOS genetic network is responsible for the repair/bypass of DNA damage in
      bacterial cells. While the initial stages of the response have been well
      characterized, less is known about the dynamics of the response after induction
      and its shutoff. To address this, we followed the response of the SOS network in
      living individual Escherichia coli cells. The promoter activity (PA) of SOS genes
      was monitored using fluorescent protein-promoter fusions, with high temporal
      resolution, after ultraviolet irradiation activation. We find a temporal pattern
      of discrete activity peaks masked in studies of cell populations. The number of
      peaks increases, while their amplitude reaches saturation, as the damage level is
      increased. Peak timing is highly precise from cell to cell and is independent of
      the stage in the cell cycle at the time of damage. Evidence is presented for the
      involvement of the umuDC operon in maintaining the pattern of PA and its temporal
      precision, providing further evidence for the role UmuD cleavage plays in
      effecting a timed pause during the SOS response, as previously proposed. The
      modulations in PA we observe share many features in common with the oscillatory
      behavior recently observed in a mammalian DNA damage response. Our results, which
      reveal a hitherto unknown modulation of the SOS response, underscore the
      importance of carrying out dynamic measurements at the level of individual living
      cells in order to unravel how a natural genetic network operates at the systems
      level.

PMID- 15954803
TI  - Review: Cromer and DAF: role in health and disease.
AB  - The antigens of the Cromer blood group system are located on the protein decay
      accelerating factor (DAF). This system consists of ten high-prevalence and three
      low-prevalence antigens; the molecular basis for all of these antigens is a
      single nucleotide polymorphism in the DAF gene. DAF is a 70,000-Da plasma
      membrane protein that is widely distributed on all blood cells and on endothelial
      and epithelial tissues. The physiological role of DAF is to inhibit the
      complement cascade at the level of the critical C3 convertase step. By this
      mechanism,DAF acts to protect autologous cells and tissues from complement
      mediated damage and hence can play a role in preventing or modulating autoimmune
      disease and inflammation. The use of recombinant DAF as a therapeutic agent in
      autoimmunity and inflammation, and of DAF transgenic animals in
      xenotransplantation, is being actively investigated. Additionally, DAF serves as
      a receptor for certain strains of Escherichia coli and certain types of
      enteroviruses. The DAF protein that contains the Cromer antigens serves important
      roles in health and disease.

PMID- 15954805
TI  - Review: acute Donath-Landsteiner hemolytic anemia.

PMID- 15954804
TI  - Novel molecular basis of an Inab phenotype.
AB  - The Cromer blood group system consists of ten high-prevalence and three low
      prevalence antigens carried on decay-accelerating factor (DAF). DAF is found in
      the cell membranes of RBCs, granulocytes, platelets, and lymphocytes and is
      widely represented in other body tissues. Sequence analyses of DNA were performed
      on a blood sample from a 91-year-old Japanese woman whose serum contained an
      alloantibody to a high-prevalence antigen in the Cromer blood group system (anti
      IFC). A blood sample from her daughter was also studied. Sequence analysis
      revealed a substitution of 508C7>T in exon 4 of DAF in the proband. The proband's
      daughter was heterozygous for 508C/T. This study describes an Inab phenotype in
      which the 508C>T nonsense mutation is predicted to change arginine at amino acid
      residue 136 to a stop codon. This change is in SCR 3 of DAF. This study reports
      on the molecular basis of a new proband with the Inab phenotype who had no
      history of intestinal disorders.

PMID- 15954806
TI  - Severe hemolytic anemia due to auto anti-N.
AB  - Auto anti-N is infrequently encountered and, in most reported cases, does not
      cause clinical hemolysis. This case reports an auto anti-N associated with severe
      hemolytic anemia (Hb=2.7 g/dL) in a 6-year-old Caucasian girl with a history of
      vomiting, fever, and abdominal pain. Upon admission, she was found to have a
      metabolic acidosis, secondary to her severe anemia, with abnormal liver function
      tests. As in three other case reports, the autoimmune hemolytic anemia resolved,
      with disappearance of the auto anti-N, after corticosteroid therapy.

PMID- 15954807
TI  - Analysis of SERF in Thai blood donors.
AB  - The Cromer blood group system consists of nine high-prevalence and three low
      prevalence antigens carried on decay-accelerating factor (DAF). We recently
      described one of these Cromer highprevalence antigens,SERF, the absence of which
      was found in a Thai woman. The lack of SERF antigen in this proband was
      associated with a substitution of nucleotide 647C>T in exon 5 of DAF, which is
      predicted to be a change of proline to leucine at amino acid position 182 in
      short consensus repeat (SCR) 3 of DAF. This study reports on PCR-RFLP analysis of
      the SERF allele with BstNI restriction endonuclease on more than one thousand
      Thai blood donor samples. One new donor homozygous (647T) and 21 donors
      heterozygous (647C/T) for the SERF allele were found. Among this cohort of random
      Thai blood donors, the SERF allele frequency was 1.1 percent. Thus, like other
      alleles in the Cromer blood group system, SERF is found in a certain ethnic
      group.

PMID- 15954808
TI  - Review: the Scianna blood group system.

PMID- 15954810
TI  - Burn healing with a diode laser: 670 nm at different doses as compared to a
      placebo group.
AB  - OBJECTIVE: A study on burn healing in rats was initiated using a diode laser at
      varied doses for determination of optimum dosimetry and treatment schedule.
      MATERIALS AND METHODS: A number of male Sprague-Dawley rats were randomly
      assigned to several groups. Anesthesia (a mixture of ketamine HCl and Xylocaine)
      was administered intraperitoneally. Burn on both flanks was created using a
      preheated metal probe and measured daily using a caliper. The right side of the
      treated rats was irradiated five times and three times per week. Slopes from the
      actual burn areas were obtained and compared against the control with the healing
      rate calculated and expressed in percent. RESULTS: In reference to the control
      group, no significant difference in healing was observed. In comparing both
      treatment schedules, there was likewise no significant difference at any day in
      both age-groups. Notably in younger rats, accelerated healing was observed with
      the highest rate in the lower range of doses (1 and 5 J/cm2), 12.4% and 11.6%,
      respectively. CONCLUSION: This experiment affirms that the beneficial effect on
      burn healing in rats is indeed affected by an interplay of several factors.

PMID- 15954811
TI  - Biological effects of helium-neon laser irradiation on normal and wounded human
      skin fibroblasts.
AB  - OBJECTIVE: This study aimed to investigate a number of structural, cellular, and
      molecular responses to heliumneon (632.8 nm) laser irradiation following a single
      dose of 0.5, 2.5, 5, or 10 J/cm2 on normal and wounded human skin fibroblasts.
      BACKGROUND DATA: Low-level laser therapy (LLLT) is a form of phototherapy,
      involving the application of low-power monochromatic and coherent light to
      injuries and lesions to stimulate healing. 1 This therapy has been successfully
      used for pain attenuation and to induce wound healing in nonhealing defects. 2
      METHODS: Changes in normal and wounded fibroblast cell morphology were evaluated
      by light microscopy. Cellular parameters evaluated cell proliferation, cell
      viability, and cytotoxicity while molecular parameters assessed the extent of DNA
      damage. RESULTS: The results clearly demonstrate that LLLT has an effect on
      normal and wounded(3) human skin fibroblasts. The parameters showed that doses of
      0.5, 2.5, 5, and 10 J/cm2 were sufficient to produce measurable changes in
      fibroblast cells. CONCLUSION: A dose of 10 J/cm2 appeared to produce a
      significant amount of cellular and molecular damage, which could be an important
      consideration for other therapies, such as photodynamic therapy.

PMID- 15954812
TI  - Shear bond strength to enamel of primary teeth irradiated with varying Er:YAG
      laser energies and SEM examination of the surface morphology: an in vitro study.
AB  - OBJECTIVE: This study aimed to assess in vitro the influence of Er:YAG laser
      energy on the shear bond strength of a total-etch adhesive system to lased enamel
      of primary teeth, and to observe by SEM the morphological appearance of laser
      ablated enamel surfaces. MATERIALS AND METHODS: For the SBS test, primary canines
      were assigned to four groups (n = 12): a control (G1) and three groups irradiated
      with different Er:YAG laser energies- 60 mJ/2 Hz (G2), 80 mJ/2 Hz (G3), and 100
      mJ/2 Hz (G4). In all groups, enamel surfaces were acidetched, Single Bond was
      applied, and resin cylinders were fabricated from Z250 resin. Bond strength was
      tested in shear (0.5 mm/min). For morphological analysis, 21 specimens were
      irradiated using the same energies, with or without acid-etching, and observed by
      SEM. RESULTS: SBS means, in MPa, were: G1-14.28 (+/-3.24); G2-18.48 (+/-4.58); G3
      17.82 (+/-4.38); G4-16.59 (+/-5.40). Overall, Er:YAG laser ablation of primary
      teeth enamel, prior to the adhesive protocol, influenced the shear bond strength.
      Bond strengths recorded after irradiation with energies of 60 and 80 mJ were
      statistically similar among them (p > 0.05), and both were superior to those
      yielded by the acid-etched control group (p < 0.05). No significant difference (p
      < 0.05) was found between bond strengths recorded for control specimens and those
      irradiated with 100 mJ. SEM analysis revealed that the increase of laser energy
      resulted in increasingly uneven and microroughened surfaces, regardless of acid
      etching association. CONCLUSIONS: The favorable results of the present study
      suggest that Er:YAG laser irradiation may be a viable approach for the
      preparation and treatment of primary teeth enamel prior to the placement of
      adhesive restorative systems.

PMID- 15954813
TI  - Effects of 670-nm phototherapy on development.
AB  - OBJECTIVE: The objective of the present study was to assess the survival and
      hatching success of chickens (Gallus gallus) exposed in ovo to far-red (670-nm)
      LED therapy. BACKGROUND DATA: Photobiomodulation by light in the red to near
      infrared range (630-1000 nm) using low-energy lasers or light-emitting diode
      (LED) arrays has been shown to accelerate wound healing and improve recovery from
      ischemic injury. The mechanism of photobiomodulation at the cellular level has
      been ascribed to the activation of mitochondrial respiratory chain components
      resulting in initiation of a signaling cascade that promotes cellular
      proliferation and cytoprotecton. MATERIALS AND METHODS: Fertile chicken eggs were
      treated once per day from embryonic days 0-20 with 670-nm LED light at a fluence
      of 4 J/cm2. In ovo survival and death were monitored by daily candling (after Day
      4). RESULTS: We observed a substantial decrease in overall and third-week
      mortality rates in the light-treated chickens. Overall, there was approximately a
      41.5% decrease in mortality rate in the light-treated chickens (NL: 20%; L:
      11.8%). During the third week of development, there was a 68.8% decrease in the
      mortality rate in light-treated chickens (NL: 20%; L: 6.25%). In addition, body
      weight, crown-rump length, and liver weight increased as a result of the 670-nm
      phototherapy. Light-treated chickens pipped (broke shell) earlier and had a
      shorter duration between pip and hatch. CONCLUSION: These results indicate that
      670-nm phototherapy by itself does not adversely affect developing embryos and
      may improve the hatching survival rate.

PMID- 15954814
TI  - Protection of skeletal muscles from ischemic injury: low-level laser therapy
      increases antioxidant activity.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of low-level laser
      therapy (LLLT) on ischemic-reperfusion (I-R) injury in the gastrocnemius muscle
      of the rat. BACKGROUND DATA: Ischemic injury in skeletal muscle is initiated
      during hypoxia and is aggravated by reoxygenation during blood reperfusion and
      accumulation of cytotoxic reactive oxygen superoxides. LLLT has been found to
      biostimulate various biological processes, such as attenuation of ischemic injury
      in the heart. MATERIALS AND METHODS: The injury was induced in the gastrocnemius
      muscles of 106 rats by complete occlusion of the blood supply for 3 h, followed
      by reperfusion. Another group of intact rats served to investigate the effect of
      LLLT on intact nonischemic muscles. Creatine phosphokinase, acid phosphatase, and
      heat shock protein were determined 7 days after I-R injury and antioxidant levels
      2 h after reperfusion. RESULTS: Laser irradiation (Ga-As, 810 nm) was applied to
      the muscles immediately and 1 h following blood supply occlusion. It was found
      that laser irradiation markedly protects skeletal muscles from degeneration
      following acute I-R injury. This was evident by significantly (p < 0.05) higher
      content of creatine phosphokinase activity and lower (p < 0.05) activity of acid
      phosphatase in the LLLT-treated muscles relative to the injured non-irradiated
      ones. The content of antioxidants and heat shock proteins was also higher (p <
      0.05) in the LLLT-treated muscles relative to that of injured non-irradiated
      muscles. CONCLUSION: The present study describes for the first time the ability
      of LLLT to significantly prevent degeneration following ischemia/reperfusion
      injury in skeletal muscles, probably by induction of synthesis of antioxidants
      and other cytoprotective proteins, such as hsp-70i. The elevation of antioxidants
      was also evident in intact muscle following LLLT. The above phenomenon may also
      be of clinical relevance in scheduled surgery or microsurgery requiring extended
      tourniquet applications to skeletal muscle followed by reperfusion.

PMID- 15954815
TI  - Effects of laser irradiation on tensile strength of bovine dentin.
AB  - OBJECTIVE: The purpose of the present study was to investigate the tensile
      strengths of dentin after laser irradiation using three kinds of dental lasers to
      elucidate the laser-irradiation effect on dentin properties. BACKGROUND DATA:
      Different kinds of laser devices have been developed in dentistry. The
      characteristics of each laser are determined by its original wavelength; however,
      one common feature is to generate heat in irradiated tissues, and such heat
      possibly affects dentin collagen, which contributes to tensile strength of the
      tissues. MATERIALS AND METHODS: Er:YAG, CO2, and diode (GaAlAs) lasers were used
      to irradiate bovine dentin. Subsequently, tensile test specimens were made from
      the irradiated dentin and tensile tests were conducted. The tensile strengths
      were analyzed using the paired-t test and Weibull analysis. Irradiated dentin was
      also observed transversally using light microscopy. RESULTS: The tensile
      strengths of the lased dentin and the control group for the Er:YAG, CO2, and
      diode lasers were 73.1 and 78.5, 70.3 and 74.3, and 64.3 and 71.0 MPa,
      respectively. The tensile strength of the dentin had a tendency to decrease with
      laser irradiation. Weibull analysis indicated that the laser influence was
      different among the three kinds of laser apparatuses and seemed to correspond to
      the depths the laser beam reached, which were suggested by light microscopy
      observation. CONCLUSION: Laser irradiation could possibly decrease dentin tensile
      strength, which suggests the importance of careful use of laser for hard tissue
      treatment, considering its energy-transforming characteristics.

PMID- 15954816
TI  - Comparison of 980- and 1064-nm wavelengths for interstitial laser thermotherapy
      of the liver.
AB  - OBJECTIVE: Interstitial laser thermotherapy (ILT) of liver tumors is generally
      performed using neodyium yttrium-aluminium-garnet (Nd-YAG) lasers. More versatile
      diode units, developed predominantly for other clinical applications, may be
      equally suitable for ILT. This study compares the efficacy of diode and Nd-YAG
      lasers in achieving maximum tissue necrosis, at low power, in a murine model.
      METHODS: Thermal ablation was induced in the liver of CBA strain mice by diode
      (980-nm wavelength) and Nd-YAG (1064-nm wavelength) lasers using 400-microm
      diameter bare fibers. Treatment time prior to tissue charring was determined for
      both lasers at a power output of 2 W. Tissue temperature was recorded upon
      completion of therapy 3 mm from the fiber insertion site. The maximum diameter of
      necrosis was accurately assessed by nicotinamide adenine dinucleotide (NADH)
      diaphorase tissue staining. RESULTS: Maximum diameter of tissue necrosis prior to
      charring occurred at 20 s (40 J) with the diode laser compared to 50 s (100 J)
      with the Nd-YAG laser. The maximum diameter of necrosis (mean [SEM]) produced by
      the diode laser, 5.9 mm (0.14), was equivalent to the necrosis induced by the Nd
      YAG laser, 5.9 mm (0.14) (p = 0.963). Tissue temperature 3 mm from the fiber
      application site immediately following ILT in the diode laser group, 40.8 degrees
      C (0.93), was not statistically different than that of the Nd-YAG laser group,
      39.0 degrees C (0.86) (p = 0.452). Tissue charring consistently prevented
      treatment beyond 20 s at 2W by the diode laser. CONCLUSION: Low power ILT with
      diode and Nd-YAG lasers achieves equivalent maximal necrosis when applied to the
      liver by a bare fiber. Treatment time to produce maximal necrosis is however
      significantly shorter with the diode laser.

PMID- 15954817
TI  - Low-level laser therapy accelerates collateral circulation and enhances
      microcirculation.
AB  - OBJECTIVE: To evaluate the efficacy of low-level laser therapy (LLLT) on
      collateral circulation and microcirculation if a blood vessel is occluded.
      BACKGROUND DATA: Investigators have attempted prostaglandin and ultrasound
      therapy to promote improvements in the vascular bed of deprived tissue after an
      injury, which may lead to occlusion of the blood vessels. MATERIALS AND METHODS:
      Thirty-four adult rabbits were used in this study, two of them considered 0-h
      reading group, while the rest were divided into two equal groups, with 16 rabbits
      each: control and those treated with LLLT. Each rabbit underwent two surgical
      operations; the medial aspect of each thigh was slit, the skin incised and the
      femoral artery exposed and ligated. The site of the operation in the treated
      group was irradiated directly following the operation and for 3 d after, one
      session daily for 10 min/session. The laser system used was a gallium-aluminum
      arsenide (Ga-Al-As) diode laser with a wavelength of 904 nm and power of 10 mW.
      Blood samples collected from the femoral artery above the site of the ligation
      were sent for examination with high-performance liquid chromatography (HPLC) to
      determine the levels of adenosine, growth hormone (GH) and fibroblast growth
      factor (FGF). Tissue specimens collected from the site of the operation,
      consisting of the artery and its surrounding muscle fibers, were sent for
      histopathological examination to determine the fiber/capillary (F/C) ratio and
      capillary diameter. Blood samples and tissue specimens were collected at 4, 8,
      12, 16, 20, 24, 48 and 72 h postoperatively from the animals of both groups,
      control and treated. RESULTS: Rapid increases in the level of adenosine, GH, and
      FGF occurred. The F/C ratio and capillary diameter peaked at 12-16 h; their
      levels declined gradually, reaching normal values 72 h after irradiation in the
      treated group. Numerous collateral blood vessels proliferated the area, with
      marked increases in the diameters of the original blood vessels. CONCLUSIONS: The
      results indicated that LLLT accelerated collateral circulation and enhanced
      microcirculation and seemed to be unique in the normalization of the functional
      features of the injured area, which could lead to occlusion of the regional blood
      vessels.

PMID- 15954818
TI  - Er:YAG laser: antimicrobial effects in the root canals of dogs' teeth with pulp
      necrosis and chronic periapical lesions.
AB  - OBJECTIVE: Our goal in this study was to evaluate the antimicrobial effect of
      Er:YAG laser applied after biomechanical preparation of the root canals of dog's
      teeth with apical periodontitis. BACKGROUND DATA: Various in vitro studies have
      reported effective bacterial reduction in infected root canals using Er:YAG
      laser. However, there is no in vivo research to support these results. METHODS:
      Forty root canals of dogs' premolar teeth with pulp necrosis and chronic
      periapical lesions were used. An initial microbiological sample was taken, and
      after biomechanical preparation was carried out, a second microbiological sample
      was taken. The teeth were divided into two groups: Group I-biomechanical
      preparation was taken of root canals without Er:YAG laser application; Group II
      biomechanical preparation was taken of root canals with Er:YAG laser application
      using 140-mJ input, 63-mJ output/15 Hz. After coronal sealing, the root canals
      were left empty for 7 days at which time a third microbiological sample was
      taken. The collected material was removed from the root canal with a #40 K file
      and placed in transport media. It was serially diluted and seeded on culture
      dishes selective for anaerobes, aerobes, and total streptococci. Colony-forming
      units per milliliter (CFU/mL) were counted. RESULTS: Groups I and II showed an
      increase of CFU/mL for all microorganisms 7 days after treatment, being
      statistically significant for anaerobes in Group I and for anaerobes and total
      streptococci in Group II. When comparing CFU/mL of Groups I and II, there was a
      statistically significant increase after 7 d for total streptococci in Group II.
      CONCLUSION: Er:YAG laser applied after biomechanical preparation did not reduce
      microorganisms in the root canal system.

PMID- 15954819
TI  - Laser light is capable of inducing proliferation of carcinoma cells in culture: a
      spectroscopic in vitro study.
AB  - OBJECTIVE: The objective of this work was to evaluate the influence of time,
      treatment, and wavelength, through the assessment of the cellular viability with
      MTT, on the proliferation of H.Ep.2 cells subjected to laser irradiation or not
      (lambda685 and lambda830 nm) with the same energy density (4 J/cm2). BACKGROUND
      DATA: Although malignant lesions have been studied for some time, there is not
      yet a definitive cure. Mortality could be reduced if lesions were diagnosed on
      initial phases of development. MATERIALS AND METHODS: H.Ep.2 cells were cultured
      in flasks and maintained in DMEN medium (10% FBS, 1% L-glutamine, and 1%
      antibiotic solution). For irradiation, cells were kept in 24 wells of the 96-well
      plaques containing DMEM medium (5% FBS, 1% L-glutamine, and 1% antibiotic
      solution), irradiated with lasers at lambda685- and lambda830-nm wavelength, and
      stained at 0, 6, 12, 24, and 48 h after irradiation. RESULTS: There was
      significant differences when the three groups were compared (p = 0.0087). There
      was significant difference for both irradiated groups, lambda685 nm (p = 0.0202)
      and lambda830 nm (p = 0.0324). Time of irradiation significantly influenced only
      the lambda685-nm group (p = 0.04). The wavelength had a significant influence (p
      = 0.013). CONCLUSION: Time, treatment, and wavelength significantly influenced
      the proliferation process of H.Ep.2 cells.

PMID- 15954820
TI  - Influence of Er:YAG laser surface treatment and primer application methods on
      microtensile bond strength self-etching systems.
AB  - OBJECTIVE: The aim of this in vitro study was to evaluate how surface preparation
      and primer application technique can influence the microtensile bond strength of
      self-etching system. BACKGROUND DATA: One of the possible applications of dental
      lasers includes increasing the quality of bond strength. MATERIALS AND METHODS:
      12 extracted, sound human molars were ground flat to expose occlusal dentin and
      were then divided into six groups (G1-G6)(n = 30-36) according to surface
      preparation and primer application (active or passive): G1-diamond bur (DB) +
      active primer (AP); G2-DB + passive primer (PP); G3-Er:YAG laser (EL) + AP; G4-EL
      + PP; G5-#600-grit paper disc (PD) + AP; G6-PD + PP. After adhesive procedure, 5
      mm high composite buildups were created with Z 250. After storage in water at 37
      degrees C for 24 h, teeth were vertically sectioned into serial 1- mm2 sticks.
      Samples were tested for tension in an Instron machine at 0.5 mm/min. Nine
      additional molars were prepared to morphological analysis. Regular grit diamond
      bur, Er:YAG laser, or #600-grit SiC paper was used for SEM observations of dentin
      surfaces of each group before and after treatment with self-etching primers.
      Microtensile data were submitted to statistical analysis. RESULTS: G1-43.85 +/-
      9.60 MPa; G2-24.28 +/- 8.90 MPa; G3-24.11 +/- 4.05 MPa; G4-23.30 +/- 4.21 MPa; G5
      55.64 +/- 8.50 MPa; G6-56.45 +/- 12.05 MPa. CONCLUSIONS: (1) Er:YAG laser and
      diamond burs are able to create distinct smear layers; however the resistance of
      dentin/adhesive interface is similar. In this way, we can use both instruments
      clinically without diminishing bond strength; (2) the #600-grit sandpaper disc
      least affects resistance and is highly recommended for in vitro studies to
      achieve standard preparation of dentinal surface; (3) active primer application
      is the method most recommended, despite the type of dentin preparation instrument
      used.

PMID- 15954821
TI  - Marginal leakage in class V cavities pretreated with different laser energy
      densities.
AB  - The purpose of the present study was to evaluate in vitro the degree of marginal
      leakage in Class V cavities involving the cementoenamel junction. Cavities were 4
      mm wide and 2 mm deep. The specimens received dentin pretreatment (37% phosphoric
      acid) followed by the Single Bond (3M) adhesive system application. The 40
      specimens were then divided into four groups: Group 1 (control); Group 2 (Nd:YAG
      laser at 120 mJ/pulse, frequency of 10 Hz, power of 1.2 W); Group 3 (Nd:YAG laser
      at 140 mJ/pulse, frequency of 10 Hz, power of 1.4 W); Group 4 (Nd:YAG laser at
      160 mJ/pulse, frequency of 10 Hz, power of 1.6 W). The cavities were restored
      with Z100 composite resin (3M) and light cured at 300-600 mW/cm2 light intensity.
      Specimens were thermocycled to 500 cycles from 2-50 degrees C. After that, they
      were dried and sealed with nail varnish, respecting 1 mm around the restorations,
      and immersed in 0.5% methylene blue solution for 4 h. After this period, the
      teeth were rinsed, dried, sectioned, and analyzed in a stereoscopic loupe. The
      highest leakage scores were considered for each specimen. The results were
      statistically analyzed by the analysis of variance (ANOVA) - Kruskal-Wallis test
      to the 5% level. For both the enamel and cementum, there was a decrease in
      marginal leakage with the application of laser energy; no significant differences
      were observed for Groups 2, 3, and 4. The results also showed a smaller tendency
      to marginal leakage on the cementum than on the enamel.

PMID- 15954822
TI  - Effects of copper vapor laser radiation on the root canal wall of human teeth: a
      scanning electron microscope study.
AB  - OBJECTIVE: The aim of this study is to analyze the effects of copper vapor laser
      radiation on the radicular wall of human teeth. MATERIALS AND METHODS:
      Immediately after the crowns of 10 human uniradicular teeth were cut along the
      cement-enamel junction, a chemical-surgical preparation of the radicular canals
      was completed. Then the roots were longitudinally sectioned to allow for
      irradiation of the surfaces of the dentin walls of the root canals. The hemi
      roots were separated into two groups: one (control) with five hemi-roots that
      were not irradiated, and another (experimental) with 15 hemi-roots divided into
      three subgroups that were submitted to the following exposure times: 0.02, 0.05,
      and 0.1 s. A opper vapor laser (510.6 nm) with a total average power of 6.5 W in
      green emission, frequency of 16.000 Hz, and pulse duration of 30 ns was used.
      RESULTS: The results obtained by scanning electron microscope analysis showed the
      appearance of a cavity in the region of laser beam impact, with melting,
      recrystallization, and cracking on the edges of the dentin of the cavity due to
      heat diffusion. CONCLUSIONS: We determined that the copper vapor laser produces
      significant morphologic changes in the radicular wall of human teeth when using
      the parameters in this study. However, further research should be done to
      establish parameters that are compatible with dental structure in order to
      eliminate thermal damages.

PMID- 15954823
TI  - 808-nm laser with exogenous chromophores for the treatment of benign oral
      lesions.
AB  - OBJECTIVE: The aim of this study was to verify the effectiveness and safety of
      the 808-nm wavelength for use on benign lesions of the oral cavity that are
      stained with toluidine blue solution. MATERIALS AND METHODS: The toluidine blue
      solution according to Mashberg is used in stomatology for the detection of leuko
      erythroplasic lesions. In our experience, we have used it to stain even serous
      cysts, angiomas, and fibromas. We chose a 808-nm wavelength emitted from a power
      diode laser, because it is well absorbed by the blue color and barely by the
      healthy mucosa. The non-contact photocoagulation kept the surrounding borders
      intact when we used the pulsed-emission, 50 ms 7 W, without anesthesia. No
      sutures were needed. The leukoplasic borders of the lesions were histologically
      examined before and after the treatment. RESULTS: The vaporized lesions healed
      completely in about 5-7 days without any kind of treatment, leaving some slight
      elastic white scars. A mild edema-erythema followed the treatment for 5-7 days.
      CONCLUSIONS: The selective results confirm the effectiveness of this therapeutic
      procedure on pigmented benign lesions, pre-treated with exogenous chromophores
      and photocoagulated without bleeding, with a minimum energy 808-nm laser.

PMID- 15954824
TI  - Effect of low-level laser therapy on Candida albicans growth in patients with
      denture stomatitis.
AB  - OBJECTIVE: The purpose of our report is to present the effect of low-level laser
      therapy on Candida albicans growth and palatal inflammation in two patients with
      denture stomatitis. BACKGROUND DATA: The most common oral mucosal disorder in
      denture wearers is denture stomatitis, a condition that is usually associated
      with the presence of the yeast Candida albicans. Different treatment methods have
      been suggested to treat this symptom, none of which is proven to be absolutely
      effective. METHODS: Two denture-wearing patients, both with palatal inflammation
      diagnosed as Newton type II denture stomatitis were treated with low-power
      semiconductor diode laser (BTL-2000, Prague, Czech Republic) at different
      wavelengths (685 and 830 nm) for 5 d consecutively. In both patients, palatal
      mucosa and acrylic denture base were irradiated in noncontact mode (probe
      distance of 0.5 cm from irradiated area) with different exposure times-5 min (830
      nm, 3.0 J/cm2, 60 mW) and 10 min (685 nm, 3.0 J/cm2, 30 mW). The effect of laser
      light on fungal growth in vivo was evaluated after the final treatment using the
      swab method and semiquantitative estimation of Candida albicans colonies growth
      on agar plates. The severity of inflammation was evaluated using clinical
      criteria. RESULTS: After lowlevel laser treatment, the reduction of yeast
      colonies on the agar plates was observed and palatal inflammation was diminished.
      CONCLUSION: LLLT is effective in the treatment of denture stomatitis. Further
      placebo controlled studies are in progress.

PMID- 15954826
TI  - Laser literature watch.

PMID- 15954825
TI  - An option for prostatectomy in the thrombocytopenic patient: a continued role for
      the Nd:YAG laser.

PMID- 15954829
TI  - Laparoscopic tension-free repair of large paraesophageal hiatal hernias with a
      composite A-shaped mesh: two-year follow-up.
AB  - BACKGROUND: Surgical repair of large hiatal hernias is associated with a high
      recurrence rate when the repair is made by simple cruroplasty. The use of a mesh
      goes from a reinforcement of a simple cruroplasty to a tension-free repair. We
      discuss the evolution of this approach and evaluate the outcomes of 27 patients
      with type II (n = 9), type III (n = 16), and type IV (n = 2) hiatal hernias
      treated laparoscopically. METHODS: Between November 1999 and October 2003, 27
      patients (18 women and 9 men) received laparoscopic repair of large hiatal
      hernias by means of an A-shaped polypropylene-polytetrafluoroethylene mesh. A
      total or a partial fundoplication was associated in all cases. The mean age was
      60.1 years (range, 36-76 years). The patients presented with symptoms of 2 months
      to 10 years in duration. Preoperative assessment included an upper
      gastrointestinal endoscopy, esophageal manometry, 24 hour pH monitoring, and
      barium swallow. Concomitant esophagitis was found in 16 patients and impaired
      esophageal peristalsis in 2 patients. Four patients had concomitant gallbladder
      disease treated at the same time. RESULTS: No conversions occurred in our series.
      There was no perioperative mortality, and morbidity was low. Follow-up averaged
      27 months (range, 6-46 months). There has been 1 recurrence (3.7%), prolonged
      dysphagia in 4 cases, and no mesh erosion. CONCLUSION: Early results confirm the
      feasibility of the tension-free repair of large hiatal hernias and the
      effectiveness of the composite A-shaped mesh. Long-term follow-up for all
      patients is necessary to determine the real incidence of recurrence.

PMID- 15954830
TI  - Early experience with laparoscopic inguinal hernia repair in a district general
      National Health Services hospital.
AB  - The introduction of laparoscopic hernia repair into the National Health Services
      (NHS) gave us an opportunity to study the feasibility and practicality of
      carrying out this modern hernia repair technique in a district general NHS
      hospital. The laparoscopic tension-free transabdominal preperitoneal (TAPP)
      method of hernia repair, as we do it, is cost-effective and efficacious. Most
      patients can be treated as day cases. We discovered incidental hernias in 18.8%
      of patients, which were treated simultaneously. A low recurrence rate (0.17%)
      with low morbidity makes it an attractive method for routine treatment of groin
      hernias in the NHS.

PMID- 15954831
TI  - Vaginohysteroscopy, a patient-friendly technique for outpatient hysteroscopy:
      experience of the first 100 cases.
AB  - OBJECTIVE: To evaluate the feasibility and tolerability of the vaginoscopic
      approach for office hysteroscopy. DESIGN: Prospective observational study.
      SETTING: Tertiary care hospital. SUBJECTS: Unselected, consecutive 100 patients
      scheduled for diagnostic hysteroscopy. INTERVENTION: Hysteroscopy with a
      vaginoscopic approach using a 5-mm rigid hysteroscope with single inflow channel,
      and normal saline for distension. OUTCOME MEASURES: Successful hysteroscopy by
      the vaginoscopic approach; operative time; and degree of pain experienced.
      RESULTS: The vaginoscopic technique was successful in 79% of the patients. The
      median operative time was 120 seconds in successful cases and 360 seconds in
      those in which the vaginoscopic approach was unsuccessful and had to be performed
      by the conventional technique with or without dilatation, the difference being
      statistically significant (P < 0.001). The procedure took < or = 2 minutes in
      91.1% (72/79) of the successful cases. No pain or mild pain was experienced by
      97.5% (77/79) of patients in whom vaginohysteroscopy was successful. CONCLUSION:
      Hysteroscopy with the vaginoscopic approach is the ideal method for outpatient
      hysteroscopy. It is feasible, quick, and very well tolerated, obviating the need
      for any analgesia or local anesthesia.

PMID- 15954832
TI  - Is minilaparoscopic inguinal hernia repair feasible? A preliminary experience.
AB  - INTRODUCTION: Laparoscopy has rapidly emerged as the preferred surgical approach
      to a number of different diseases because it allows for a correct diagnosis and
      proper treatment. It seems to be moving toward the use of mini-instruments (5 mm
      or less in diameter). The aim of this paper is to illustrate retrospectively the
      results of an initial experience of minilaparoscopic transabdominal preperitoneal
      (miniTAPP) repair of groin hernia defects performed at two institutions.
      MATERIALS AND METHODS: Between February 2000 and December 2003, a total of 303
      patients (mean age, 45 years) underwent a miniTAPP procedure: 213 patients
      (70.2%) were operated on bilaterally and 90 (28.7%) for a unilateral defect, with
      a total of 516 hernia defects repaired. The primary endpoint was the feasibility
      rate for miniTAPP. The secondary endpoint was the incidence of mini-TAPP-related
      complications. RESULTS: No conversions to laparoscopy or an anterior open
      approach were required. There were no major complications, while minor
      complications ranged as high as 0.3%. CONCLUSION: While limited by its
      retrospective design, the present study indicates that the minilaparoscopic
      approach to groin hernia repair is safe and effective, making miniTAPP a
      challenging alternative to laparoscopy in the approach to groin hernia repair.

PMID- 15954833
TI  - Laparoscopic common bile duct exploration with T-tube choledochotomy for the
      management of choledocholithiasis.
AB  - Although laparoscopic cholecystectomy (LC) has become the gold standard for the
      management of gallstone disease, the application of laparoscopic common bile duct
      exploration (LCBDE) for choledocholithiasis has been slower. The aim of this
      study is to determine the feasibility and effectiveness of LCBDE. A retrospective
      cohort study was conducted to compare LCBDE (n = 82) with conventional common
      bile duct exploration (CCBDE) (n = 75) and endoscopic sphincterotomy (EST) (n =
      80) in the management of choledocholithiasis. All our LCBDEs were performed
      through choledochotomy with T-tube placement. The mean operative time of the
      LCBDE group (124 +/- 48 minutes) was not significantly longer then the CCBDE
      group (118 +/- 35 minutes), while the postoperative hospitalization was shorter
      in both the LCBDE (8 +/- 5 days) and EST (9 +/- 4 days) groups than in the CCBDE
      (13 +/- 6 days) group. In the LCBDE group, 14 patients (17.1%) required
      postoperative choledochoscopy to clear residual stones through the T-tube tract.
      The only mortality occurred in the CCBDE group. The morbidity rate was 3.7%
      (3/82) in the LCBDE group, including bile leakage in 1 case and bile peritonitis
      in 2 cases; 6.7% (5/75) in the CCBDE group, including atlectasis in 2 cases,
      sepsis in 1, and wound infection in 2. There were 2 cases of postoperative
      pancreatitis (2.5%; 2/80) in the EST group. The difference in the average number
      of sessions needed for complete clearance of choledocholithiasis in each group
      was statistically significant (EST, 1.46 +/- 0.67; LCBDE, 1.23 +/- 0.42; and
      CCBDE, 1.09 +/- 0.28; P < 0.0001). Our results suggested that EST and LCBDE
      tended to require more therapeutic sessions then CCBDE, although these sessions
      were less invasive. The benefits of LCBDE include minimal invasiveness,
      concurrent treatment of gallbladder stone and CBD stones in a single session, and
      a shorter postoperative hospital stay. However a longer learning curve is needed.
      Selection of the most suitable therapeutic option for individual patients by an
      experienced surgeon gives the most benefits to patients.

PMID- 15954834
TI  - Laparoscopic treatment of Morgagni-Larrey hernia: technical details and report of
      a series.
AB  - Three patients with Morgagni-Larrey hernia were admitted to the surgical
      department between August 2000 and September 2003 with slight chest pain and
      dyspnea. Laparoscopic repair of the diaphragmatic hernia was performed using a
      tension-free closure of the defects with either Vicryl-Prolene or dual facing
      mesh fixed by Prolene extracorporeal knots and Endostitch devices. The patients
      were discharged on postoperative day 5 without complications. Mean follow-up has
      been 23 months (range, 15-36 months) and no recurrence or morbidity related to
      the procedure has been seen. Laparoscopic repair of Morgagni-Larrey hernia
      represents an attractive alternative to open surgery. The benefits are gentle and
      easy manipulation of the content of the sac, reduced surgical trauma, and rapid
      and uneventful recovery.

PMID- 15954835
TI  - Laparoscopic nephroureterectomy for tuberculous nonfunctioning kidneys compared
      with laparoscopic nephroureterectomy for other diseases.
AB  - OBJECTIVE: To summarize the results of 8 consecutive laparoscopic
      nephroureterectomies (LNUs) for tuberculous nonfunctioning kidneys and compare
      them with 10 LNUs performed for other benign etiologies (control group).
      MATERIALS AND METHODS: From November 1999 to February 2004, 8 patients underwent
      LNU for tuberculous ureteric stricture with a nonfunctioning kidney at our
      center. During the same time period, 10 LNUs were performed for other benign
      conditions. Hospital records were reviewed to obtain demographic data. In
      addition, operative time, intraoperative and postoperative complications,
      duration of postoperative ileus, and hospital stay was recorded. The outcomes of
      surgery for tuberculosis were compared with that for the control group. Patients
      were followed up for long-term complications of laparoscopic surgery. RESULTS:
      The two groups had a comparable demographic data. Nephroureterectomy was
      successfully performed laparoscopically in all 8 patients with tuberculosis. One
      patient in the control group, with a large staghorn renal and ureteral calculus,
      required conversion to open surgery due to dense perinephric adhesions. The
      outcome of surgery for tuberculosis was compared with outcomes in the control
      group using SPSS software. The mean operative time, blood loss, analgesic
      requirement, duration of postoperative ileus, and hospital stay of both groups
      was comparable, and the differences between them were statistically
      insignificant. CONCLUSION: The results of this study indicate that LNU for a
      tuberculous nonfunctioning kidney is a safe, effective, and less invasive
      treatment modality. Comparing our results with those of nephroureterectomy for
      other, benign diseases shows that the procedure has similar safety and efficacy
      even for tuberculous kidneys. Tuberculosis should not be considered a
      contraindication for a laparoscopic approach. Laparoscopic nephroureterectomy
      should be offered as the treatment modality of choice to all patients with
      tuberculous nonfunctioning kidney whose disease involves the kidney and ureters.

PMID- 15954836
TI  - Limitations of fluoroscopic intraoperative cholangiography in cases suggestive of
      choledocholithiasis.
AB  - BACKGROUND: Fluoroscopic intraoperative cholangiography (IOC) has been proposed
      as a safe and accurate screening method for choledocholithiasis, with a
      sensitivity and specificity of nearly 100% in selected cases. In the present
      study we retrospectively reviewed the diagnostic accuracy of IOC in cases highly
      suggestive of choledocholithiasis. MATERIALS AND METHODS: Between January 1999
      and December 2002, 103 patients underwent IOC as an imaging method for common
      bile duct (CBD) stone detection. We did not routinely perform IOC in all patients
      who were submitted to laparoscopic cholecystectomy, reserving the method for
      patients with a high probability of choledocholithiasis, namely patients with a
      history or the presence of painful obstructive jaundice at the time of referral,
      patients with a history of mild acute pancreatitis of biliary origin, and
      patients with abnormalities in their liver biochemistry profile as measured by
      liver function tests (LFT). RESULTS: The mean rates of sensitivity, specificity,
      positive predictive value (PPV), and negative predictive value (NPV) for IOC were
      98%, 94%, 94.5%, and 98% for the whole series, respectively. The diagnostic
      accuracy was 100% in patients with a history of obstructive jaundice or liver
      biochemical derangement, but was less in patients with a history of biliary
      pancreatitis. There were 3 false positive cases and 1 case of false negative
      results, all of which occurred in the subgroup of patients with a history of
      pancreatitis. CONCLUSION: Selective fluoroscopic IOC is generally feasible and
      safe, as well as highly accurate (100%) for CBD stone detection in patients with
      obstructive jaundice or abnormal LFT. The PPV of the method decreases in patients
      with a history of pancreatitis (75%), while a negative result is highly
      suggestive of the absence of CBD stones (NPV = 98%). The present study concluded
      in a higher incidence of false results in patients with a normal size CBD,
      suggesting that the diagnostic accuracy of IOC is probably related to the size of
      the CBD rather than the indication for its performance.

PMID- 15954837
TI  - Retained common bile duct stone as a consequence of a fundus-first laparoscopic
      cholecystectomy.
AB  - The fundus-first technique for laparoscopic cholecystectomy provides an
      alternative to the conventional dissection technique in patients at high risk for
      conversion to open cholecystectomy or at risk for bile duct injury. We report the
      complication of a retained common bile duct (CBD) stone after utilizing this
      technique. Intraoperative cholangiography (IOC) was not performed due to the
      concern for causing CBD injury in a patient with significant periductal
      inflammation and no risk factors for CBD stones. Following discharge, the patient
      developed scleral icterus 3 days later and returned for evaluation. He required
      endoscopic retrograde cholangiopancreatography for removal of a CBD stone. None
      of the four series reporting on this technique have described this complication.
      It should now be recognized that there is a risk of displacing a gallstone into
      the CBD in utilizing this technique. This report highlights the importance of
      intraoperative imaging of the CBD when using this technique, even in patients
      considered to be at low risk for having CBD stones. If IOC is considered
      hazardous, then intraoperative ultrasound should be the modality of choice.

PMID- 15954838
TI  - Single-session laparoscopic radical and contralateral partial nephrectomy.
AB  - Renal tumor is likely to become one of the most important indications for
      laparoscopic surgery. We present an old woman, who underwent single-session
      laparoscopic nephrectomy and contralateral partial nephrectomy due to bilateral
      kidney tumor. The advantages of simultaneous bilateral intervention are reduced
      psychological stress, single anaesthesia, less medication, less blood loss,
      shorter hospital stay and convalescence, and considerable cost-effectiveness.

PMID- 15954839
TI  - Laparoscopic resection of appendiceal mucinous cystadenoma.
AB  - Mucinous cystadenoma is a rare lesion of the vermiform appendix and is seldom
      diagnosed before surgery, although radiologic and ultrasonographic findings have
      been reported. We present the case of a 65-year-old female with rheumatoid
      arthritis who presented with general malaise, poor appetite, fever, and right
      upper and lower quadrant pain of about one week's duration. Abdominal sonography
      and computed tomography revealed an 8 x 4 x 3 cm cystic lesion of the appendix.
      Laparoscopic evaluation confirmed this finding and the lesion was resected
      without rupturing the tumor during manipulation. Laparoscopic surgery provides
      the advantages of good exposure and evaluation of entire abdominal cavity, as
      well as more rapid recovery. It is important to avoid tumor rupture during
      manipulation, and formation of pseudomyxoma peritonei, in case the tumor is
      malignant.

PMID- 15954840
TI  - Nontraumatic perforation of the bile duct treated with laparoscopic surgery.
AB  - Nontraumatic perforation of the bile duct (NPB), which has also been reported as
      spontaneous perforation of the bile duct, is a disease in which spontaneous
      perforation occurs in the wall of the extrahepatic or intrahepatic duct without
      any traumatic or iatrogenic injury. Although NPB in adults is extremely rare, we
      have treated two such patients using a laparoscopic technique. Both cases
      presented with intra-abdominal abscesses associated with common bile duct stones,
      and laparoscopic surgery for those conditions was initially performed. During the
      procedure, NPB was identified in the right intrahepatic duct in one case and in
      the left intrahepatic duct in the other case. Laparoscopic surgery consisting of
      common bile duct exploration, T-tube placement, cholecystectomy, and abscess
      drainage was safely performed in both cases. Both patients eventually recovered
      without major complications. Although NBP is an uncommon disease, it can be
      treated successfully with a laparoscopic procedure.

PMID- 15954841
TI  - Tracheal reaction to three different intraluminal stents in an animal model of
      tracheomalacia.
AB  - Three different internal airway stents were studied in an animal model of
      tracheomalacia: the Palmaz stent (Johnson & Johnson, Warren, New Jersey) and the
      NIR stent (Medinol Ltd., Tel Aviv, Israel)--both made of stainless steel in the
      form of tubular mesh--and the Nitinol stent, made of nickel-titanium formed into
      a spiral shape. All three stents could be adequately stabilized in the malacic
      tracheal segment. The Nitinol stent (Medinol Ltd., Tel Aviv, Israel) proved to be
      less reactive to the tracheal mucosa, demonstrated higher biocompatibility with
      significantly less granulation tissue formation, and showed superior radial
      resistance. Extraction of the Nitinol stent also proved to be much smoother. This
      stent may be the stent of choice in the treatment of tracheo- and bronchomalacia.

PMID- 15954842
TI  - Empyema management: twelve years' experience since the introduction of video
      assisted thoracoscopic surgery.
AB  - We reviewed empyema management at our center since video-assisted thoracoscopic
      surgery (VATS) was introduced. Between 1991 and 2003, 58 patients (34 male, 24
      female) ages 1 day to 17 years (median, 6 years) were identified. The median
      interval from the onset of symptoms to presentation was 7 days; 31% of patients
      received inpatient care at another hospital, and 24% were from northern
      communities, including the Arctic. Symptoms included fever (100%), cough (66%),
      shortness of breath (46%), chest pain (38%), and abdominal pain (17%). Most
      patients (96%) had pneumonia. The most common organisms were Streptococcus
      pneumoniae (22%), group A streptococcus (8%), and Mycobacterium tuberculosis
      (3%). No organisms were identified in 31% of patients. One empyema was trauma
      related and one was due to complications of esophageal stricturoplasty. All
      patients received intravenous antibiotics (median, 17 days). Three patients had
      thoracentesis, 17 had chest tubes, 3 had thoracentesis and chest tubes, 26 had
      VATS, 6 had thoracotomy, and 3 had minithoracotomy. Median operative times were
      86 minutes for VATS, 90 minutes for thoracotomy, and 75 minutes for
      minithoracotomy. Median total length of stay (LOS) was 15 days for VATS, 20.5
      days for thoracotomy, and 21 days for minithoracotomy. The median preoperative
      LOS was longer for thoracotomy (10 days) than for VATS (5 days) or
      minithoracotomy (1 day). The median postoperative LOS was 14 days for VATS, 9.5
      days for thoracotomy, and 8 days for minithoracotomy. Our experience shows that
      VATS is a safe and effective approach to managing children with empyema. The
      shorter preoperative LOS for VATS is likely due to earlier surgical referral and
      intervention using less invasive surgical procedures.

PMID- 15954843
TI  - Removal of an unexpected tracheal foreign body after five months.
AB  - Foreign body aspiration can produce serious pulmonary diseases. Timely diagnosis
      and appropriate treatment is important to prevent long-term complications in
      affected children. We report the case of a 15-month-old child with a 5-month
      history of regurgitation, vomiting, recurrent tracheobronchitis, and pneumonia.
      The diagnosis was gastroesophageal reflux. The laryngotracheal endoscopy revealed
      a rabbit vertebra partially obstructing the airway at the level of the cricoid
      cartilage. With a rigid bronchoscope and forceps equipped with a telescope, it
      was possible to disengage and extract the foreign body. Six months later
      endoscopic control revealed no residual alterations in the larynx and trachea.

PMID- 15954844
TI  - Protein families and their evolution-a structural perspective.
AB  - We can now assign about two thirds of the sequences from completed genomes to as
      few as 1400 domain families for which structures are known and thus more ancient
      evolutionary relationships established. About 200 of these domain families are
      common to all kingdoms of life and account for nearly 50% of domain structure
      annotations in the genomes. Some of these domain families have been very
      extensively duplicated within a genome and combined with different domain
      partners giving rise to different multidomain proteins. The ways in which these
      domain combinations evolve tend to be specific to the organism so that less than
      15% of the protein families found within a genome appear to be common to all
      kingdoms of life. Recent analyses of completed genomes, exploiting the structural
      data, have revealed the extent to which duplication of these domains and
      modifications of their functions can expand the functional repertoire of the
      organism, contributing to increasing complexity.

PMID- 15954845
TI  - Amphotericin B deoxycholate: time to retire our old standard?

PMID- 15954849
TI  - Oritavancin: a new avenue for resistant Gram-positive bacteria.
AB  - Oritavancin, a new semisynthetic glycopeptide has a spectrum of activity similar
      to vancomycin, although it exhibits potent antimicrobial activity against
      vancomycin-resistant staphylococci and enterococci species. It has a long
      terminal half-life of 360 h, is highly protein bound and has been dosed once
      daily in clinical trials. Oritavancin has been studied in complicated skin and
      skin structure infections where it was noninferior to the comparator group of
      vancomycin/cephalexin. Thus far, oritavancin has a favorable side-effect profile
      and appears promising in the treatment of multidrug resistant Gram-positive
      bacteria.

PMID- 15954850
TI  - Sertaconazole: updated review of a topical antifungal agent.
AB  - Sertaconazole is an imidazole-type antifungal agent that has shown considerable
      in vitro activity against pathogenic fungi. Various studies carried out in animal
      models, clinical and toxicologic trials have confirmed the value of sertaconazole
      in the topical treatment of superficial mycoses in dermatology and gynecology.
      After several years of clinical experience in the topical treatment of
      dermatophytosis and Tinea versicolor, the substance has been approved for
      gynecologic candidiasis in Europe. Sertaconazole has a wide action spectrum that
      includes yeasts and dermatophyte fungi, and it is also active against bacteria,
      mainly Gram-positive cocci, making it highly efficient in the treatment of
      polymicrobial infections. The recent approval of the molecule by the US Food and
      Drug Administration, and the appearance of a new formulation of sertaconazole for
      the treatment of onychomycoses on a weekly administrative basis, are all data
      relevant to the process of marketing the product.

PMID- 15954851
TI  - Role of linezolid in the treatment of orthopedic infections.
AB  - Gram-positive organisms, particularly staphylococci and streptococci, are
      responsible for the majority of bone and joint infections. The rising incidence
      of antimicrobial resistance among Staphylococcus aureus, coagulase-negative
      staphylococci and enterococci means that novel antibiotics with unique mechanisms
      of antimicrobial activity are needed, especially in orthopedic infections.
      Linezolid is the first of the oxazolidinones, a new class of antibacterial agents
      particularly effective against Gram-positive infections including methicillin-
      and vancomycin-resistant strains. With an excellent oral bioavailability and
      acceptable safety profile, linezolid offers a valuable alternative to more
      traditional therapies, such as glycopeptides. No large randomized trials have
      been published on its use in patients with orthopedic infections, but early
      results are encouraging. Reported adverse events, especially bone marrow
      suppression and optic neuropathy seen with prolonged administration, mean that
      treatment of such patients must be undertaken with careful follow-up of
      laboratory tests. Until now, little resistance has been reported.

PMID- 15954853
TI  - Pharmacokinetic/pharmacodynamic evaluation of anti-infective agents.
AB  - Pharmacokinetic/pharmacodynamic modeling has become an extremely important tool
      in evaluating and optimizing anti-infective therapy. By systematically linking
      the pharmacokinetic and pharmacodynamic properties of the anti-infective agent,
      it is possible to make educated decisions about the correct drug to be used,
      correct dosing regimen and to estimate the probability of success with the
      selected dose regimen. This article gives an overview of the current
      pharmacokinetic/pharmacodynamic approaches for anti-infective agents and
      discusses their use in optimizing drug therapy.

PMID- 15954852
TI  - Extended release amoxicillin/clavulanate: optimizing a product for respiratory
      infections based on pharmacodynamic principles.
AB  - Acute bacterial respiratory tract infections cause a great deal of human
      morbidity and mortality. Treatment guidelines for these infections include
      macrolides, doxycycline, beta-lactams and beta-lactam/beta-lactamase inhibitor
      combinations such as amoxicillin/clavulanic acid to provide coverage for the
      common respiratory pathogens, including penicillin and macrolide nonsusceptible
      Streptococcus pneumoniae, as well as beta-lactamase-producing Haemophilus
      influenzae and Moraxella catarrhalis. In response to recent guidelines
      recommending higher dose amoxicillin to extend coverage to a higher percentage of
      S. pneumoniae, a new formulation of amoxicillin/clavulanic acid was developed.
      This formulation includes a higher amoxicillin dose, with part of the amoxicillin
      dose being in an extended release formulation, without increasing the clavulanate
      dose, for twice-daily oral treatment of these infections. Clinical studies of
      community-acquired pneumonia and acute rhinosinusitis have shown that the new
      formulation is well tolerated and highly efficacious, with clinical outcomes
      equivalent to comparators.

PMID- 15954854
TI  - Therapy of hepatitis C in patients with HIV infection.
AB  - Hepatitis C is found in approximately a third of patients infected with HIV.
      Therapy of hepatitis C in HIV patients is very important from several view
      points. First, hepatitis C in the setting of immunosuppression may progress
      faster, although recent data show that mortality from liver disease was decreased
      in highly active antiretroviral therapy. HIV/hepatitis C coinfection is
      associated with more frequent elevation in liver tests (drug-induced liver
      injury) during highly active antiretroviral therapy, and in some studies,
      hepatitis C has been associated with lower CD4+ recoveries. The therapeutic
      standard of care is a combination of peginterferon and ribavirin at a fixed dose,
      800 mg/day, although higher ribavirin doses may further improve virologic
      outcomes. In patients that do not respond virologically, maintenance therapy with
      peginterferon monotherapy is a potential avenue to stem the advance of liver
      fibrosis, although controlled data in coinfected patients are needed to issue
      formal recommendations.

PMID- 15954855
TI  - Antiviral therapy for genital herpes infections in pregnancy.
AB  - One of the most deleterious consequences of maternal infection with herpes
      simplex virus is neonatal herpes, which results in death or significant
      neurodevelopmental impairment in the majority of infected babies. Herpes simplex
      virus infection during pregnancy can also impact the psychologic health of the
      mother. The ability to minimize the risk of herpes simplex virus transmission has
      improved in tandem with advances in understanding of the mechanisms and
      epidemiology of acquisition of neonatal herpes simplex virus. In particular,
      antiviral pharmacotherapy is now recognized as an important option both for
      reducing the risk of transmission of herpes simplex virus from a seropositive to
      a seronegative partner and, potentially, for modifying several risk factors for
      transmission of the virus from a herpes simplex virus-infected mother to the
      neonate. This review discusses the consequences and management of herpes simplex
      virus infection during pregnancy, with a focus on the evolving role of antiviral
      therapy.

PMID- 15954856
TI  - Prevention of infectious complications in severe acute pancreatitis with systemic
      antibiotics: where are we now?
AB  - Infectious complications are the leading cause of death in patients with severe
      acute pancreatitis. Currently, there is controversy concerning the therapeutic
      possibilities to reduce the incidence of bacterial infection in this disease.
      Numerous studies are available which apparently support the prophylactic use of
      antibiotics in patients with necrotizing pancreatitis. The results, however, are
      contradicting and interpretation is difficult as these studies have used various
      antibiotic drugs with different application schemes and heterogeneous study end
      points. This article gives a critical overview of the background of antibiotic
      treatment in severe acute pancreatitis, the published data on antibiotic
      treatment and an outlook on the topics that need to be addressed by future
      research.

PMID- 15954857
TI  - Cephalosporin resistance among animal-associated Enterobacteria: a current
      perspective.
AB  - Beta-lactam antimicrobials are an important class of drugs used for the treatment
      of infection. Resistance can arise by several mechanisms, including the
      acquisition of genes encoding beta-lactamases from other bacteria, alterations in
      cell membrane permeability and over expression of endogenous beta-lactamases. The
      acquisition of beta-lactamase resistance genes by both Salmonella and Escherichia
      coli appears to be on the rise, which may pose potential problems for the
      treatment of infections in both human and animal medicine. The prudent use of
      clinically important antimicrobials is therefore critical to maintain their
      effectiveness. Where possible, the use of newer generation cephalosporins should
      be limited in veterinary medicine.

PMID- 15954858
TI  - Therapeutic strategies for human microsporidia infections.
AB  - Over the past 20 years, microsporidia have emerged as a cause of infectious
      diseases in AIDS patients, organ transplant recipients, children, travelers,
      contact lens wearers and the elderly. Enterocytozoon bieneusi and the
      Encephalitozoon spp., Encephalitozoon cuniculi, Encephalitozoon hellem and
      Encephalitozoon intestinalis, are the most frequently identified microsporidia in
      humans, and are associated with diarrhea and systemic disease. The microsporidia
      are small, single-celled, obligately intracellular parasites that have been
      identified in water sources, as well as in wild, domestic and food-producing farm
      animals, thereby raising concerns for waterborne, foodborne and zoonotic
      transmission. Current therapies for microsporidiosis include albendazole, a
      benzimidazole that inhibits microtubule assembly and is effective against several
      microsporidia, including the Encephalitozoon spp., although it is less effective
      against Encephalitozoon bieneusi. Fumagillin, an antibiotic and antiangiogenic
      compound produced by Aspergillus fumigatus, is more broadly effective against
      Encephalitozoon spp. and E. bieneusi; however, is toxic when administered
      systemically to mammals. Recent studies are also focusing on compounds that
      target the microsporidia polyamines (e.g., polyamine analogs), methionine
      aminopeptidase 2 (e.g., fumagillin-related compounds), chitin inhibitors (e.g.,
      nikkomycins), topoisomerases (e.g., fluoroquinolones) and tubulin (e.g.,
      benzimidazole-related compounds).

PMID- 15954859
TI  - Management of Pneumocystis pneumonia in patients with inflammatory disorders.
AB  - Pneumocystis jirovecii is an atypical fungus that causes Pneumocystis pneumonia
      in immunocompromised patients. Underlying diseases associated with Pneumocystis
      pneumonia mainly consist of hematologic malignancies, solid tumors, organ
      transplant recipients and inflammatory disorders. Currently, inflammatory
      disorders represent 20% of underlying diseases. Corticosteroids are considered as
      a major risk factor. Recently introduced immunosuppressive drugs, such as
      antitumor necrosis factor monoclonal antibodies, could enhance the risk of
      Pneumocystis pneumonia. In patients with inflammatory disorders, lymphopenia is
      probably a determining factor but CD4+ T-cell count associated with the risk of
      Pneumocystis pneumonia remains unassessed. The diagnosis is based upon clinical,
      radiologic and biologic data. The identification of P. jirovecii usually requires
      a lower respiratory tract specimen, even if oral washes samples seem to be
      promising. According to recent data, immunofluorescent stains should be
      considered as the new gold standard, and specialized techniques such as PCR
      should be applied for sputum samples or oral washes. Recommendations on
      prophylaxis remains controversial except in patients with Wegener's
      granulomatosis and systemic lupus erythematosus. Cotrimoxazole is the preferred
      agent for prophylaxis as well as for treatment. An adjunctive corticosteroid
      therapy is usually prescribed despite the lack of evidence for utility in
      patients with inflammatory disorders. As person-to-person transmission is the
      most likely mode of acquiring P. jirovecii, isolation precautions should be
      advised.

PMID- 15954860
TI  - Role of inhaled antibacterials in hospital-acquired and ventilator-associated
      pneumonia.
AB  - Inhaled antibiotics are not usually considered outside the setting of cystic
      fibrosis or Pneumocystis jiroveci prophylaxis. However, because they deliver high
      drug concentrations at the site of infection with negligible systemic absorption
      and toxicity, they are logical compliments to standard intravenous therapy for
      severe nosocomial pneumonias -- particularly those caused by multiresistant
      organisms. Older studies that have shown marginal or no benefit have either
      applied inhaled antibiotics indiscriminately to low risk populations, or have
      used crude delivery systems, such as hand atomizers or poured it into the
      endotracheal tube. Although inhaled antibiotics cannot be recommended for
      prevention of nosocomial pneumonia at this time, a few studies involving
      prophylaxis have shown promising trends, particularly in high-risk patients with
      predisposing conditions. The greatest potential of inhaled antibiotics lies in
      the treatment of severe healthcare-associated pneumonia caused by a
      multiresistant organism. The method of delivery is extremely important. Trials
      that have shown the most benefit, even against pathogens most difficult to
      eradicate and in damaged lungs, have used optimized delivery systems. Most
      authorities recommend using ultrasonic or vibrating disk nebulizers to generate
      particle sizes between 1 and 5 microm that are crucial for deposition in terminal
      bronchioles and alveoli. Inhaled liposomal amphotericin has also demonstrated
      encouraging results in animal trials. Recently, inhaled phytochemicals were
      successfully employed in the treatment of a patient with primary pulmonary
      tuberculosis. When used selectively in high-risk patients, or in the treatment of
      established pneumonia, inhaled antibiotics have not been associated with
      development of resistant organisms.

PMID- 15954861
TI  - Enhanced catabolism of mitochondrial superoxide/hydrogen peroxide and aging in
      transgenic Drosophila.
AB  - The generation of superoxide anion radicals (O2*-) and hydrogen peroxide (H2O2)
      during mitochondrial respiration has been widely postulated to be causally linked
      to the aging process. The hypothesis that a specific enhancement of mitochondrial
      O2*-/H2O2 catabolism would delay age-associated physiological changes and extend
      the lifespan was tested by simultaneous overexpression of MnSOD (manganese
      superoxide dismutase) and catalase, ectopically targeted to the mitochondrial
      matrix of transgenic Drosophila melanogaster. The increased activities of these
      antioxidative enzymes resulted in a decrease of mitochondrial H2O2 release and
      enhancement of free methionine content. The MnSOD/mitochondrial catalase
      transgenic flies displayed an enhanced resistance to experimental oxidative
      stress, induced by dietary H2O2 administration or by exposure to 100% ambient
      oxygen. However, the lifespan of the flies was decreased, by up to 43%, and this
      effect coincided with (i) an overall decrease in physical fitness, as measured by
      the speed of walking, and (ii) an age-related decrease in mitochondrial state 3
      (ADP-stimulated) respiration. These findings support the notion that
      mitochondrial O2*-/H2O2 production at physiological levels is essential for
      normal biological processes leading to the attainment of a normal lifespan.

PMID- 15954862
TI  - Conformational changes in dynamin on GTP binding and oligomerization reported by
      intrinsic and extrinsic fluorescence.
AB  - The effects of guanine nucleotides on the intrinsic and extrinsic fluorescence
      properties of dynamin were assessed. The intrinsic Trp (tryptophan) fluorescence
      spectra of purified recombinant dynamin-1 and -2 were very similar, with a
      maximum at 332 nm. Collisional quenching by KI was weak (approximately 30%),
      suggesting that the majority of Trp residues are buried. Binding of guanine
      nucleotides decreased intrinsic fluorescence by 15-20%. Titration of the effects
      showed that GTP and GDP bound to a single class of non-interacting sites in
      dynamin tetramers with apparent dissociation constants (K(d)) values of 5.4 and
      7.4 microM (dynamin-1) and 13.2 and 7.1 microM (dynamin-2) respectively. Similar
      dissociation constant values for both nucleotides were obtained by titrating the
      quenching of IAEDANS [N-iodoacetyl-N'-(5-sulpho-1-naphthyl)ethylenediamine]
      labelled dynamin-2. Despite the similar binding affinities, GTP and GDP result in
      different conformations of the protein, as revealed by sensitivity to proteinase
      K fragmentation. Dynamins contain five Trp residues, of which four are in the PH
      domain (pleckstrin homology domain) and one is in the C-terminal PRD
      (proline/arginine-rich domain). Guanine nucleotides quenched fluorescence
      emission from a truncated (DeltaPRD) mutant dynamin-1 to the same extent as in
      the full-length protein, suggesting conformational coupling between the G
      (groove)-domain and the PH domain. Efficient resonance energy transfer from PH
      domain Trp residues to bound mant-GTP [where mant stands for 2'-(3')-O-(N
      methylanthraniloyl)] suggests that the G-domain and PH domain are in close
      proximity (5-6 nm). Promotion of dynamin-2 oligomerization, by reduction in ionic
      strength or increasing protein concentration, had little effect on intrinsic
      dynamin fluorescence. However, fluorescence emission from IAEDANS.dynamin-2
      showed a significant spectral shift on oligomerization. In addition, energy
      transfer was observed when oligomerization was promoted in mixtures of
      IAEDANS.dynamin-2 and 4-(4-dimethylaminophenylazo)benzoic acid-coupled dynamin-2,
      an effect that was counteracted by GTP but not GDP.

PMID- 15954864
TI  - A novel alpha-glucosidase from the acidophilic archaeon Ferroplasma acidiphilum
      strain Y with high transglycosylation activity and an unusual catalytic
      nucleophile.
AB  - Ferroplasma acidiphilum strain Y (DSM 12658), a ferrous iron-oxidizing,
      acidophilic and mesophilic archaeon, was found to produce a membrane-bound alpha
      glucosidase (alphaGluFa) showing no significant similarity to any of the known
      glycoside hydrolases classified in different families and having an unusual
      catalytic site consisting of a threonine and a histidine residue. The highest
      alpha-glucosidase activity was found at low pH, 2.4-3.5, and the substrate
      preference order was: sucrose>maltose>maltotriose >>maltotetraose>>malto
      oligosaccharides from maltopentaose to maltoheptaose>>>soluble starch (kcat/K(m)
      was 293.0, 197.0, 18.8, 0.3 and 0.02 s(-1) x mM(-1) respectively). The enzyme was
      able to transfer glucosyl groups from maltose as donor, to produce exclusively
      maltotriose (up to 300 g/l). Chemical modification and electrospray ionization MS
      analysis of 5-fluoro-alpha-D-glucopyranosyl-enzyme derivatives, coupled with site
      directed mutagenesis, strongly suggested that the putative catalytic nucleophile
      in this enzyme is Thr212. Iron was found to be essential for enzyme activity and
      integrity, and His390 was shown to be essential for iron binding. These results
      suggest that the metalloenzyme alphaGluFa is a new member of the glycosyl
      hydrolase family that uses a novel mechanism for sugar glycosylation and/or
      transglycosylation.

PMID- 15954863
TI  - Ras plasma membrane signalling platforms.
AB  - The plasma membrane is a complex, dynamic structure that provides platforms for
      the assembly of many signal transduction pathways. These platforms have the
      capacity to impose an additional level of regulation on cell signalling networks.
      In this review, we will consider specifically how Ras proteins interact with the
      plasma membrane. The focus will be on recent studies that provide novel spatial
      and dynamic insights into the micro-environments that different Ras proteins
      utilize for signal transduction. We will correlate these recent studies
      suggesting Ras proteins might operate within a heterogeneous plasma membrane with
      earlier biochemical work on Ras signal transduction.

PMID- 15954865
TI  - An essential dimer-forming subregion of the endoplasmic reticulum stress sensor
      Ire1.
AB  - The luminal domain of the type I transmembrane protein Ire1 senses endoplasmic
      reticulum stress by an undefined mechanism to up-regulate the signalling pathway
      for the unfolded protein response. Previously, we proposed that the luminal
      domain of yeast Ire1 is divided into five subregions, termed subregions I-V
      sequentially from the N-terminus. Ire1 lost activity when internal deletions of
      subregion II or IV were made. In the present paper, we show that partial
      proteolysis of a recombinant protein consisting of the Ire1 luminal domain
      suggests that subregions II-IV are tightly folded. We also show that a
      recombinant protein of subregions II-IV formed homodimers, and that this
      homodimer formation was impaired by an internal deletion of subregion IV.
      Furthermore, recombinant fragments of subregion IV exhibited a self-binding
      ability. Therefore, although its sequence is little conserved evolutionarily,
      subregion IV plays an essential role to promote Ire1 dimer formation.

PMID- 15954867
TI  - Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review*.
AB  - OBJECTIVES: To assess and quantify the relationship between polycystic ovaries
      (PCOs) and ovarian hyperstimulation syndrome (OHSS). DATA SOURCES: Published
      studies, any language, identified through MEDLINE, EMBASE, BIOSIS, Web of
      Science, and bibliographies. Studies were selected if exposure (ultrasound
      findings of PCO before treatment) and outcome (OHSS) could be abstracted to two
      by-two tables. RESULTS: Ten studies, meeting inclusion and exclusion criteria,
      were analyzed. When PCO were present, the combined odds ratio for OHSS was 6.8
      (95% confidence interval 4.9-9.6). CONCLUSION: There is a significant and
      consistent relationship between PCO and OHSS. When PCO are present before
      treatment with assisted reproduction, deliberate policies to moderate treatment
      appear justified.

PMID- 15954866
TI  - Weaning induces NOS-2 expression through NF-kappaB modulation in the lactating
      mammary gland: importance of GSH.
AB  - At the end of lactation the mammary gland undergoes involution, a process
      characterized by apoptosis of secretory cells and tissue remodelling. To gain
      insight into this process, we analysed the gene expression profile by
      oligonucleotide microarrays during lactation and after forced weaning. Up
      regulation of inflammatory mediators and acute-phase response genes during
      weaning was found. Expression of IkappaBalpha (inhibitory kappaBalpha), a protein
      known to modulate NF-kappaB (nuclear factor-kappaB) nuclear translocation, was
      significantly up-regulated. On the other hand, there was a time-dependent
      degradation of IkappaBalpha protein levels in response to weaning, suggesting a
      role for NF-kappaB. Furthermore, we have demonstrated, using chromatin
      immunoprecipitation assays, binding of NF-kappaB to the NOS-2 (inducible nitric
      oxide synthase) promoter at the early onset of events triggered during weaning.
      The three isoforms of NOS are constitutively present in the lactating mammary
      gland; however, while NOS-2 mRNA and protein levels and, consequently, NO
      production are increased during weaning, NOS-3 protein levels are diminished.
      Western blot analyses have demonstrated that protein nitration is increased in
      the mammary gland during weaning, but this is limited to a few specific tyrosine
      nitrated proteins. Interestingly, inhibition of GSH synthesis at the peak of
      lactation partially mimics these findings, highlighting the role of NO production
      and GSH depletion during involution.

PMID- 15954868
TI  - The effect of magnesium sulfate treatment on serum cardiac troponin I levels in
      preeclamptic women.
AB  - AIM: To investigate serum cardiac troponin I levels before and after magnesium
      sulfate treatment in preeclamptic pregnant women. MATERIALS AND METHODS: Fifty
      five pregnant women were included in the prospectively planned study. Study group
      patients (n = 25) were pregnant women hospitalized with a preeclampsia diagnosis
      while the control group (n = 30) were pregnant women with no medical or obstetric
      problem who had been attending the antenatal clinic. Serum cardiac troponin I
      levels were compared in the normal pregnant women and in preeclamptic pregnant
      women. These levels were also compared in the preeclamptic women before and after
      magnesium sulfate treatment. Mann-Whitney U-test was used for statistical
      analysis. RESULTS: Groups were similar with respect to age, gravity, parity, and
      gestational age. The median serum cardiac troponin I levels in preeclamptic
      patients was 0.20 ng/ml (0.02-4.53) before treatment and 0.09 ng/ml (0.02-3.91)
      after treatment, while it was 0.02 ng/ml (0.0-0.05) in the control group. The
      serum cardiac troponin I level in the preeclamptic group was significantly high
      (P < 0.01), and pretreatment values in this group were significantly higher
      compared with post-treatment values (P < 0.01) CONCLUSION: Cardiac troponin I is
      a sensitive parameter for indicating minor myocardial damage which may occur in
      preeclampsia and for evaluating the efficiency of magnesium sulfate treatment.

PMID- 15954869
TI  - Period of gestational diabetes mellitus diagnosis and maternal and fetal
      morbidity.
AB  - BACKGROUND: The aim of the study was to analyze the association between the
      period of diagnosis of gestational diabetes mellitus (GDM) and maternal and
      neonatal outcome. METHODS: In this retrospective study, 1708 offspring (1571
      singleton, 119 twins, and 18 triplets) born to women with GDM who attended the
      Diabetic and Pregnancy Clinic were included. Pregnancies were divided into three
      groups according to the gestational age at GDM diagnosis. The association of the
      period of diagnosis with maternal and fetal outcome was assessed adjusting for
      potentially confounding variables (logistic regression analysis). RESULTS: The
      period of diagnosis was a predictor in two out of three maternal outcomes
      (pregnancy-induced hypertension and insulin treatment) and in four out of 12
      fetal outcomes (preterm birth, 5-min Apgar <7, perinatal mortality, and
      hyperbilirubinemia). Whereas pregnancy-induced hypertension was higher in women
      diagnosed with GDM in the second period, the other outcomes displayed higher
      occurrences with earlier diagnosis. CONCLUSIONS: Diagnosis of GDM earlier in
      pregnancy is a predictor of adverse maternal and neonatal outcome.

PMID- 15954870
TI  - Outpatient misoprostol cervical ripening without subsequent induction of labor to
      prevent post-term pregnancy.
AB  - BACKGROUND: Interventions that may help shorten the duration of pregnancy in an
      African setting where facilities for fetal monitoring in post-term pregnancy are
      limited, and induction is not without its hazards, are needed. AIM: To determine
      whether outpatient administration of intravaginal misoprostol safely decreases
      the interval to delivery in postdate pregnancies. DESIGN: Open randomized
      controlled trial. SETTING: Zonal district hospitals, Kwale, Southern Nigeria
      (August 2000 to October 2001). METHODS: Seventy-seven women were randomized at 40
      weeks gestation to receive either 25 microg misoprostol intravaginally (38) or
      gentle cervical assessment only (39) on an outpatient basis. Subjects were then
      allowed to go into spontaneous labor unless an indication for induction
      developed. MAIN OUTCOME MEASURES: Interval to delivery, duration of labor, and
      incidence of side-effects. RESULTS: Misoprostol was associated with significant
      decrease in mean time to delivery (4.5 +/- 4.1 versus 7.4 +/- 5.2 days; P =
      0.008), earlier gestational age at delivery (40.6 +/- 0.6 versus 41.4 +/- 0.05
      weeks; P < 0.001) and shorter duration of active labor (6.1 +/- 4.0 versus 8.2 +/
      5.3 h; P = 0.028), without any significant increase in fetal distress, low Apgar
      score at delivery or other side-effects. CONCLUSION: Outpatient administration of
      low-dose misoprostol can safely shorten the length of gestation in postdate
      pregnancies.

PMID- 15954871
TI  - Interleukin-6 in preterm premature rupture of membranes as an indicator of
      neonatal outcome.
AB  - BACKGROUND: The aim of this study was to investigate whether the levels of
      interleukin-6 (IL-6) can be used as markers of adverse outcome in preterm
      neonates born after preterm premature rupture of membranes (PPROM). METHODS: This
      study involved 109 preterm neonates and their mothers. The PPROM group consisted
      of 58 neonates who were born after PPROM, and the control group consisted of 51
      neonates. IL-6 levels were measured in umbilical cord blood, maternal blood
      sampled during delivery and in neonatal blood taken on the fourth day of life.
      RESULTS: In the PPROM group, IL-6 concentrations in maternal blood, cord blood,
      and neonatal blood were significantly higher in neonates with sepsis, compared
      with those without sepsis (P < 0.001). Choosing 108.5 pg/ml as a cut-off
      concentration of IL-6 in umbilical cord blood for neonatal sepsis resulted in
      sensitivity 95%, specificity 100%, positive predictive value 100%, and negative
      predictive value 97.4%. Concerning IL-6 in maternal blood, a cut-off
      concentration of 81 pg/ml showed sensitivity 90%, specificity 97.4%, positive
      predictive value 94.7%, and negative predictive value 94.9%. Eighteen of 20
      neonates with early sepsis and seven of nine neonates, who died in the PPROM
      group, were born of mothers with IL-6 levels above the cut-off concentration in
      their blood during delivery. CONCLUSIONS: IL-6 in umbilical cord blood was the
      most significant variable for predicting early onset sepsis in preterm neonates.
      IL-6 in maternal blood was indicative of intrauterine environmental threats and
      might be used to identify pregnancies where intervention would be appropriate.

PMID- 15954872
TI  - Socioeconomic status and use of postmenopausal hormone replacement therapy among
      Danish women.
AB  - BACKGROUND: Observational studies on hormone replacement therapy (HRT) have shown
      cardioprotective effects that have not been replicated in randomized controlled
      trials, perhaps due to unaccounted confounding by socioeconomic factors. To
      resolve this discrepancy, we examined the association between socioeconomic
      status (SES) and HRT use in a large population of Danish postmenopausal women.
      METHODS: We conducted a register-based cross-sectional study based on all women
      aged 40 or more with a permanent address in the North Jutland County, Denmark on
      1 January 1999 (n = 122 584). The women were classified according to SES through
      the Prevention Registry at Statistics Denmark. Through the Pharmaco
      epidemiological Prescription Database, we identified all reimbursed HRT
      prescriptions in North Jutland County for women aged 40 or more in the study
      population during 1999. We calculated 1-year prevalence proportions of HRT use
      for all socioeconomic groups. Between-group comparisons were made by log-risk
      analysis with adjustment for age. RESULTS: The estimated overall user-prevalence
      of HRT in 1999 among Danish postmenopausal women was 14.9%[95% confidence
      interval (CI) 14.7-15.1]. No substantial socioeconomic gradient was found in the
      study. The adjusted relative prevalence proportions (RPPs) varied between 0.90
      and 1.14 among the different groups when using salaried employees, basic level,
      as the reference group. CONCLUSIONS: Our findings suggest that recent
      observational studies on the use of hormone replacement therapy among women in
      Denmark may not have suffered from strong confounding by socioeconomic status.

PMID- 15954873
TI  - The effect of gynecologic age, body mass index and psychosocial environment on
      menstrual regularity among teenaged females.
AB  - BACKGROUND: The aim was to study the prevalence of menstrual irregularity at an
      early postmenarcheal age and various biopsychosocial factors associated with
      menstrual irregularity. METHODS: The study was conducted in Tartu, Estonia. The
      70-item questionnaire and the 21-item Beck Depression Inventory (BDI) were
      completed by 580 female students of grades 9-12 in four high schools. Their
      height and weight were measured and body mass index (BMI) calculated. The effects
      associated with regularity of the menstrual cycle were studied. RESULTS:
      Irregularity of the menstrual cycle was reported by 40% of respondents at an
      early postmenarcheal age. The risks for irregular menstrual cycles (IRM) were BMI
      <17.5 kg/m(2)[odds ratio (OR) 2.06; 95% confidence interval (95% CI) 1.06-4.00],
      low economic status IRM [OR 1.77 (95% CI 1.41-2.20)], insufficient communication
      with parents [OR 1.46 (95% CI 1.02-2.09)], and never pleased to go to school [OR
      1.27 (95% CI 1.03-1.56)]. Comparison of the answers to the BDI with the
      regularity of periods revealed a difference in the total score [OR 1.54 (95% CI
      1.21-1.97)], with a mean score of 8.3 +/- 0.4 for the respondents with regular
      menstrual cycles (RM) vs. 10.6 +/- 0.5 for the respondents with IRM. CONCLUSION:
      Menstrual irregularity at an early postmenarcheal age can be considered as an
      indicator of difficulties in psychosocial adaptability of teenaged females.

PMID- 15954874
TI  - Is preoperative vaginal cleansing necessary for control of infection after first
      trimester vacuum curettage?
AB  - BACKGROUND: Traditionally, the vagina is cleansed, before a curettage is
      performed. A previous study, comparing cleansing with chlorhexidine solution and
      cleansing with saline solution before vacuum aspiration in the first trimester,
      did not show any difference in the frequency of postoperative pelvic inflammatory
      disease. We wanted to investigate whether this was true also for vaginal
      cleansing with chlorhexidine, compared to no vaginal cleansing at all. METHODS:
      Consecutive women having surgical first trimester legal abortions were randomized
      to vulvar and vaginal cleansing with chlorhexidine or vulvar cleansing only. The
      frequency of postabortion pelvic inflammatory disease was evaluated with patient
      questionnaires and study of medical records. RESULTS: Of the 486 patients
      included in the study, vaginal cleansing was performed on 246 and no vaginal
      cleansing on 240. The frequency of probable pelvic inflammatory disease was 2.4%
      with cleansing and 2.1% without cleansing (no significant difference).
      CONCLUSIONS: Under certain conditions, preoperative vaginal cleansing can be
      safely omitted.

PMID- 15954875
TI  - High birthweight and shoulder dystocia: the strongest risk factors for
      obstetrical brachial plexus palsy in a Swedish population-based study.
AB  - BACKGROUND: Obstetrical brachial plexus palsy (OBPP) is a serious form of
      neonatal morbidity. OBJECTIVE: The aim of this work was to study the incidence of
      OBPP and to analyze its risk factors. METHODS: This is a population-based
      retrospective case-control study. All deliveries recorded in the Swedish Medical
      Birth Registry between 1987 and 1997 (n = 1 213 987) were investigated. Cases (n
      = 2399) with OBPP were compared to all other cases. RESULTS: The incidence of
      OBPP increased from 0.17 in 1987 to 0.27% in 1997 (p = 0.002). During the same
      time period, the mean birthweight increased from 3483 to 3525 g. Birthweight
      increasing from 4000 g was associated with a progressive rise in OBPP risk. Other
      significant risk factors associated with the injury were shoulder dystocia,
      breech presentation in vaginal delivery, operative vaginal delivery, diabetes
      mellitus, induction of labor, protracted active phase, secondary arrest of
      dilatation, and epidural anesthesia. Cesarean section was associated with a
      decreased risk of OBPP. If 5000 g is chosen as cut-off for cesarean section, 85%
      of the infants in this weight class are underestimated using ultrasonography.
      Approximately, 331 abdominal deliveries have to be performed to avoid one case of
      OBPP. CONCLUSIONS: Shoulder dystocia and infant birthweight of 4500 g and more
      are the strongest risk factors for OBPP in a Swedish population.

PMID- 15954876
TI  - Use of Sengstaken-Blakemore tube in massive postpartum hemorrhage: a series of 17
      cases.
AB  - BACKGROUND: To evaluate the efficacy and identify the indications of intrauterine
      tamponade with a Sengstaken-Blakemore tube in acute postpartum hemorrhage.
      METHODS: Retrospective study was performed in 17 female patients with massive
      postpartum hemorrhage despite appropriate medical treatment, and requiring
      surgery (embolization techniques were not available in our hospital). Patients
      were treated by inserting a Sengstaken-Blakemore tube in the uterus through the
      vagina in case of vaginal delivery or through the hysterotomy incision in case of
      cesarean section. The esophageal balloon was inflated with 250 ml of isotonic
      saline solution. Patients underwent regional or general anesthesia. A preventive
      treatment with broad-spectrum antibiotics was systematically administered.
      RESULTS: Tamponade treatment prevented surgery in 88% of patients, hemorrhage was
      controlled in 71% of cases (reducing the need for embolization by 80%), and
      waiting for a transfer for embolization was made possible for 18% of patients.
      CONCLUSION: Intrauterine tamponade with a Sengstaken-Blakemore tube appears as a
      simple, low-cost, readily available and effective means of treating life
      threatening postpartum hemorrhage. The only apparent contraindication is the
      discovery of an infection during delivery.

PMID- 15954877
TI  - Mode of delivery in pregnant women with hypertensive disorders and unfavorable
      cervix following induction of labor with vaginal application of prostaglandin E.
AB  - BACKGROUND: Our aim was to evaluate the mode of delivery in pregnant women with
      hypertensive disorders and unfavorable cervix following induction of labor with
      vaginal application of prostaglandin E(2) (PGE(2)) near or at term, and to define
      the predictors of successful vaginal delivery in such women. METHODS: In a
      retrospective case-controlled study, pregnant women with hypertension, who
      underwent labor induction with PGE(2) tablets (study group, n = 284), were
      compared with women, who underwent elective induction of labor (group 2, n =
      115), and women with normal spontaneous onset of labor (group 3, n = 510).
      RESULTS: The rate of cesarean section (CS) was significantly higher in the study
      group (25.3%) than in group 2 (14.8%) and in group 3 (9%). Exclusion of the
      nulliparous women from the study and control groups yielded similar CS rates in
      the study group (16.9%) and in group 2 (11.1%). Women with pre-eclampsia and the
      women with chronic hypertension or pregnancy-induced hypertension had similar
      rates of CS. In logistic regression model, nulliparity, induction of labor with
      PGE(2), and maternal age, but not hypertensive disorders, were independently and
      significantly associated with increased risk of CS. CONCLUSIONS: PGE(2) induction
      of labor is successful in approximately 75% of patients with hypertensive
      disorders and unfavorable cervix, with apparently no serious maternal or fetal
      complications. The induction of labor by itself, and not the hypertensive
      disorders in pregnancy, is independent risk factor for CS.

PMID- 15954878
TI  - Lack of proinflammatory effects of free fatty acids on human umbilical cord vein
      endothelial cells and leukocytes.
AB  - AIM: To determine whether the free fatty acids (FFAs), oleic, linoleic, and
      palmitic acid, found elevated before 20 weeks of pregnancy in those women who
      later develop preeclampsia, induced changes in expression of the vascular cell
      adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), or E
      selectin in cultured human umbilical cord vein endothelial cells (HUVEC), and
      integrin subunit CD11b, L-selectin or intracellular reactive oxygen species (ROS)
      in leukocytes. METHODS: The VCAM-1, ICAM-1, and E-selectin expression were
      measured using ELISA in HUVEC after incubation with 100 micromol of either oleic,
      linoleic, or palmitic acid for 6 hr and 24 hr. The co-reactivity with
      lipopolysaccharide (LPS), the amount of VCAM-1 mRNA in the cells, and soluble
      VCAM-1 in the incubation medium were measured as well. Leukocyte adhesion
      molecules and ROS were measured after incubation with 750 microm of either of the
      FFAs in a whole blood model using flow cytometry. RESULTS: No effects of the FFAs
      tested were found on the HUVEC or leukocyte adhesion molecule expression or
      intracellular ROS. The only exception to this was palmitic acid incubation, which
      significantly lowered the VCAM-1 expression in HUVEC after 24-hr incubation and
      also slowed the decay of VCAM-1 expressed after stimulation with LPS.
      CONCLUSIONS: The lack of significant proinflammatory changes of the FFAs tested
      might indicate that the elevated plasma levels of FFAs seen in preeclampsia most
      probably are products of the preeclamptic process rather than a causative factor.

PMID- 15954879
TI  - Tumor suppressor and growth regulatory genes are overexpressed in severe early
      onset preeclampsia--an array study on case-specific human preeclamptic placental
      tissue.
AB  - BACKGROUND: Preeclampsia is an important clinical condition with unknown
      etiology. We used DNA array technique to compare placental gene expression
      profile in severe early-onset preeclampsia from 25 to 27 gestational weeks with
      strictly non-affected placental samples from similar gestational weeks. METHOD:
      DNA arrays were validated by showing the up-regulation of several genes typical
      for preeclampsia such as chorionic gonadotrophin beta-chain, tissue factor
      pathway inhibitor, and intercellular adhesion molecule-1. In DNA array, 5% of
      genes displayed less than or equal to twofold increase in expression level and
      only 0.2% of genes showed < or =0.5-fold decrease in expression in preeclampsia
      versus control. Signs of immunological factors, hypoxia, apoptosis, oxidative
      stress and altered thrombosis, coagulation as well as endothelial injury were
      seen in the gene expression profile. RESULTS: As a new finding, we identified a
      group of 13 genes with a function in tumor suppression and growth regulation
      which were significantly up-regulated in preeclampsia. Three out of the five most
      highly up-regulated genes belonged to this group which included genes, such as
      protein phosphatase 2, phospholipid scramblase 1, transcription elongation
      factor, melanoma adhesion molecule, retinoic acid receptor responder 3, and
      RANTES. CONCLUSIONS: It is concluded that up-regulation of tumor suppressor and
      growth regulatory genes may play an important role in the pathogenesis of severe
      early-onset preeclampsia.

PMID- 15954880
TI  - Panniculectomy in gynecologic cancer surgical procedures by using a harmonic
      scalpel.
AB  - OBJECTIVE: To demonstrate that panniculectomy in obese gynecologic oncology
      patients undergoing surgical gynecologic procedures reduces operative time, gives
      better surgical exposure and does not increase the number of operative
      complications. METHODS: A retrospective review of 90 patients who had
      panniculectomy at the time of gynecologic surgery between 1992 and June 2003.
      Analyzed data included indication for surgery, patient's weight, operative times,
      blood loss and complications. RESULTS: Panniculectomy was performed in 20
      patients operated because of uterine cervix cancer and 70 because of uterine body
      cancer. The mean age was 57.3 years, weight 126.7 kg and body mass index (BMI) 47
      kg/m(2). The following procedures were performed: radical hysterectomy by the
      Wertheim-Meigs method (22 cases), total hysterectomy (68 cases) with bilateral
      salpingoophorectomy, pelvic lymphadenectomy and also periaortal lymphadenectomy
      (four cases). The mean operative time was 169 min, including from 20 to 25 min
      opening and closing time, and blood transfusion was undertaken in 15.6% of
      patients. The average weight of removed panniculus was 4900 g. In 82.2% of
      patients there were no wound complications, in 17.8% the healing was delayed.
      Daily drains secretion was 65.3 mL (range 0-300 mL). One patient died because of
      pulmonary embolism, and another because of myocardial infarction. There were no
      cases of damage to the urinary tract, intestines or large vessels. During the
      histopathological examination metastatic carcinoma in lymph nodes was found in
      29.3% of the cases. CONCLUSIONS: Massively obese women can safely undergo
      gynecologic oncological surgery with simultaneous panniculectomy. Panniculectomy
      improves surgical access and facilitates radical surgery.

PMID- 15954881
TI  - Autotransplantation of cryopreserved ovarian tissue to the right forearm 4(1/2)
      years after autologous stem cell transplantation.

PMID- 15954882
TI  - Use of traditional Chinese herbal medicine during pregnancy: a prospective
      survey.

PMID- 15954883
TI  - Abdominal pregnancy: ultrasound diagnosis aided by the balloon of a Foley
      catheter.

PMID- 15954884
TI  - Orbital metastases of unknown origin: HPV typing identifies the primary tumor.

PMID- 15954885
TI  - A benign leiomyoma causing paraparesis: a case report and histopathogenesis.

PMID- 15954886
TI  - Pure primary squamous cell carcinoma of the ovary: a case report and review of
      the literature.

PMID- 15954887
TI  - Sphincter rupture and anal incontinence.

PMID- 15954888
TI  - Obesity and pregnancy.

PMID- 15954891
TI  - Chronic renal allograft rejection: pathophysiologic considerations.
AB  - Chronic rejection is currently the most prevalent cause of renal transplant
      failure. Clinically, chronic rejection presents by chronic transplant
      dysfunction, characterized by a slow loss of function, often in combination with
      proteinuria and hypertension. The histopathology is not specific in most cases
      but transplant glomerulopathy and multilayering of the peritubular capillaries
      are highly characteristic. Several risk factors have been identified such as
      young recipient age, black race, presensitization, histoincompatability, and
      acute rejection episodes, especially vascular rejection episodes and rejections
      that occur late after transplantation. Chronic rejection develops in grafts that
      undergo intermittent or persistent damage from cellular and humoral responses
      resulting from indirect recognition of alloantigens. Progression factors such as
      advanced donor age, renal dysfunction, hypertension, proteinuria, hyperlipidemia,
      and smoking accelerate deterioration of renal function. At the tissue level,
      senescence conditioned by ischemia/reperfusion (I/R) may contribute to the
      development of chronic allograft nephropathy (CAN). The most effective option to
      prevent renal failure from chronic rejection is to avoid graft injury from both
      immune and nonimmune mechanism together with nonnephrotoxic maintenance
      immunosuppression.

PMID- 15954892
TI  - Pathophysiology of contrast medium-induced nephropathy.
AB  - BACKGROUND: Contrast medium-induced nephropathy (CIN) is a well-known cause of
      acute renal failure, but the development of CIN remains poorly understood. A
      number of studies have been performed with the one aim, to shed some light onto
      the pathophysiology of CIN. These have led to manifold interpretations and
      sometimes contradicting conclusions. METHODS: This review critically surveys
      mechanisms believed to mediate CIN by highlighting the complex pathophysiologic
      entity, including altered rheologic properties, perturbation of renal
      hemodynamics, regional hypoxia, auto- and paracrine factors [adenosine,
      endothelin, and reactive oxygen species (ROS)], and direct cytotoxic effects.
      Moreover, the importance of physicochemical properties of contrast media are made
      clear. RESULTS: The more recently developed iso-osmolar contrast media are
      dimers, not monomers as the widely used nonionic low osmolar contrast media. The
      dimers have physicochemical features different from other contrast media which
      may be of clinical importance, not only with respect to osmolality. The viscosity
      of the commercially available dimers is considerably higher than blood.
      CONCLUSION: Many experimental studies provide evidence for a greater perturbation
      in renal functions by dimeric contrast media in comparison to nonionic monomeric
      contrast media. Clinical trials have yielded conflicting results.

PMID- 15954893
TI  - Fish mesonephric model of polycystic kidney disease in medaka (Oryzias latipes)
      pc mutant.
AB  - BACKGROUND: Polycystic kidney disease (PKD) is a common hereditary disease. A
      number of murine and zebrafish mutants have been generated and used for the study
      of PKD as metanephric and pronephric models, respectively. Here, we report a
      medaka (Oryzias latipes) mutant that develops numerous cysts in the kidney in
      adulthood fish in an autosomal-recessive manner as a mesonephric model of PKD.
      METHODS: The phenotypes of the medaka pc mutant were described in terms of
      morphologic, histologic, and ultrastructural features. The pc see-through stock
      was produced by crossing a pc mutant and a fish from the see-through stock and
      used for observing the kidney through the transparent body wall of a live fish.
      RESULTS: The mutant developed bilateral massive enlargement of the kidney in
      adulthood. They sexually matured normally within 2 months of age and died within
      6 months of age. The affected kidney was occupied by numerous, fluid-filled
      cysts, which were lined by attenuated squamous epithelial cells. Developmentally,
      cystic formation began in the pronephros in 10-day-old fry and in the mesonephros
      in 20-day-old fry at the microscopic level. The pc see-through stock was useful
      in observing disease progression in live fish. CONCLUSION: The kidney disorder
      that develops in the medaka pc mutant is a mesonephric counterpart of PKD,
      particularly an autosomal-dominant PKD, based on its morphologic, histologic, and
      ultrastructural features, and slow progression.

PMID- 15954894
TI  - Lipoxin A4 inhibits TNF-alpha-induced production of interleukins and
      proliferation of rat mesangial cells.
AB  - BACKGROUND: Studies have shown that lipoxin A(4) (LXA(4)) and its analogues
      inhibited proliferation of glomerular mesangial cells induced by leukotriene D(4)
      (LTD(4)) or platelet-derived growth factor (PDGF), reduced the production of
      proinflammatory cytokines such as interleukin (IL)-1beta and IL-6 in renal tissue
      of ischemic injury. In the present studies, we examine whether LXA(4) have
      inhibitory effects on tumor necrosis factor-alpha (TNF-alpha)-induced productions
      of IL-1beta and IL-6 and proliferation of glomerular mesangial cells of rat, and
      explore the molecular mechanisms of signal pathway of LXA(4). METHODS: Cultured
      glomerular mesangial cells were treated with TNF-alpha (10 ng/mL), with or
      without preincubation with LXA(4) at the different concentrations. Cell
      proliferation was assessed by [(3)H]-thymidine incorporation. Proteins of IL
      1beta and IL-6 in supernatant were analyzed by enzyme-linked immunosorbent assay
      (ELISA). Expressions of mRNA of IL-1beta and IL-6 were determined by real-time
      polymerase chain reaction (PCR) and cyclin E by reverse transcription (RT)-PCR.
      Proteins of cyclin E, threonine phosphorylated Akt(1) at 308 site (Thr(308)) and
      p27(kip1) were analyzed by Western blotting studies. Activities of signal
      transducers and activators of transcription-3 (STAT(3)), nuclear factor-kappaB
      (NF-kappaB) were determined by electrophroretic mobility shift assay (EMSA).
      Expression of Src homology (SH) 2-containing protein-tyrosine phosphatase (SHP-2)
      was assessed by immunoprecipitation and immunoblotting. RESULTS: TNF-alpha
      stimulated proliferation, release of proteins and expressions of mRNA of IL-1beta
      and IL-6 in mesangial cells were inhibited by LXA(4) in a dose-dependent manner.
      The marked increments in mRNA expression and protein synthesis of cyclin E
      induced by TNF-alpha in parallel with proliferation of mesangial cells were down
      regulated by LXA(4). LXA(4) antagonized the phosphorylation of SHP-2 and activity
      of NF-kappaB induced by TNF-alpha. Pretreatment of the cells with NF-kappaB
      inhibitor pyrrolidine dithio-carbamate (PDTC) blocked the productions of IL
      1beta, IL-6, and activation of NF-kappaB induced by TNF-alpha. Stimulation of
      mesangial cells with TNF-alpha resulted in enhanced DNA-binding activity of
      STAT(3). This increment was inhibited by LXA(4) in a dose-dependent manner.
      Threonine phosphorylated Akt(1) protein at 308 site stimulated by TNF-alpha was
      reduced by LXA(4.) TNF-alpha-induced decrement in expression of p27(kip1) protein
      was ameliorated by LXA(4) in a dose-dependent manner. CONCLUSION: TNF-alpha
      induced proliferation and increment of cyclin E of rat mesangial cells can be
      inhibited by LXA(4), and these inhibitory effects might be through the mechanisms
      of STAT(3) and Akt(1)/p27(kip1) pathway-dependent signal transduction. LXA(4)
      also antagonized TNF-alpha-stimulated IL-1beta and IL-6 synthesis, and these
      antagonisms were related to SHP-2 and NF-kappaB pathway-dependent signal
      transduction.

PMID- 15954895
TI  - Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced
      chronic glomerulosclerosis.
AB  - BACKGROUND: A critical role of soluble guanylate cyclase and nitric oxide
      dependent cyclic 3',5'-guanosine monophosphate (cGMP) production for glomerular
      matrix expansion has recently been documented in a rat model of acute anti-thy1
      glomerulonephritis. The present study analyzes the renal activity of the nitric
      oxide-cGMP signaling cascade in and the effect of the specific soluble guanylate
      cyclase stimulator Bay 41-2272 on a progressive model of anti-thy1-induced
      chronic glomerulosclerosis. METHODS: Anti-thy1 glomerulosclerosis was induced by
      injection of anti-thy1 antibody into uninephrectomized rats. One week after
      disease induction, animals were randomly assigned to chronic glomerulosclerosis,
      chronic glomerulosclerosis plus Bay 41-2272 (10 mg/kg body weight/day) or chronic
      glomerulosclerosis plus hydralazine (15 mg/kg body weight/day). In week 16,
      analysis included effects on systolic blood pressure, proteinuria, kidney
      function, glomerular and tubulointerstitial matrix protein accumulation,
      expression of transforming growth factor-beta1 (TGF-beta1), fibronectin and
      plasminogen activator inhibitor type 1 (PAI-1), macrophage infiltration, cell
      proliferation, basal and nitric oxide-stimulated cGMP production as well as
      tubulointerstitial mRNA expression of alpha 1 and beta 1 soluble guanylate
      cyclase. RESULTS: The moderately elevated systolic blood pressure seen in the
      chronic glomerulosclerosis group was comparably decreased by both treatments.
      Compared to normal controls, soluble guanylate cyclase mRNA expression and nitric
      oxide-stimulated cGMP production were up-regulated in the tubulointerstitium of
      the untreated chronic glomerulosclerosis animals, while its activity was
      decreased in glomeruli. Bay 41-2272 treatment enhanced glomerular and
      tubulointerstitial nitric oxide-cGMP signaling significantly. This went along
      with markedly reduced glomerular and tubulointerstitial macrophage infiltration,
      number of proliferating cells, matrix expression and accumulation, as well as
      improved kidney function. In contrast, hydralazine therapy did not significantly
      affect renal nitric oxide-cGMP signaling, macrophage number, cell proliferation,
      matrix protein expression and accumulation. CONCLUSION: Glomerular and
      tubulointerstitial soluble guanylate cyclase activity are discordantly altered in
      anti-thy1-induced chronic glomerulosclerosis. Stimulation of soluble guanylate
      cyclase signaling by Bay 41-2272 limits the progressive course of this model
      toward tubulointerstitial fibrosis and impaired renal function at least in part
      in a blood pressure-independent manner. The results suggest that soluble
      guanylate cyclase activation counteracts fibrosis and progression in chronic
      renal disease.

PMID- 15954896
TI  - Chemokine response to febrile urinary tract infection.
AB  - BACKGROUND: Mucosal CXC chemokines recruit inflammatory cells to the infected
      urinary tract. The chemokine response repertoire of the urinary tract and the
      relationship to disease severity have not been examined, however. METHODS: This
      study quantified CXC (CXCL1, CXCL3, CXCL5, CXCL8, CXCL9, and CXCL10) and CC
      (CCL2, CCL4, and CCL5) chemokines in sequential urine samples obtained from 50
      patients with febrile urinary tract infections during 24 hours after diagnosis.
      RESULTS: All patients had elevated chemokine levels, but bacteremic infections
      caused higher CXCL1, CXCL3, CXCL5, CXCL8, and CCL2 responses. CCL2 and CXCL8
      levels were higher in patients with acute pyelonephritis symptoms and CCL2,
      CXCL3, CCL4, CXCL5, and CXCL10 were significantly correlated to C-reactive
      protein (CRP) and temperature. Women and men showed different chemokine
      responses. CONCLUSION: Febrile urinary tract infections are accompanied by a
      complex chemokine response. The response magnitude reflects disease severity, and
      the repertoire is influenced by gender and underlying disease.

PMID- 15954897
TI  - Hyaluronan is apically secreted and expressed by proliferating or regenerating
      renal tubular cells.
AB  - BACKGROUND: Hyaluronan has diverse biologic functions in the body, varying from
      structural tasks to cell stress-induced CD44-mediated activation of intracellular
      signaling pathways. Hyaluronan biology is relatively unexplored in the kidney.
      Previously, we identified hyaluronan as binding molecule for crystals in the
      renal tubules. Crystal retention is a crucial early event in the etiology of
      kidney stones. The present study was performed to determine the polarized
      distribution of hyaluronan and CD44 by renal tubular cells. METHODS: Madin-Darby
      canine kidney (MDCK) strain I and primary cultures of human renal tubular cells
      were grown on permeable supports in a two-compartment culture system. Studies
      were performed during growth and after scrape-injury. Metabolic labeling studies
      and an enzyme-linked hyaluronan -binding assay were used to measure the molecular
      mass and the amount of secreted hyaluronan in apical and basal medium. Confocal
      microscopy was applied to detect membrane hyaluronan and CD44. Hyaluronan
      synthase (HAS) mRNA expression was studied with reverse transcriptase-polymerase
      chain reaction (RT-PCR). The in vitro expression profile of hyaluronan was
      compared with that in biopsies of transplanted human kidneys with acute tubular
      necrosis. RESULTS: Proliferating cells produced more hyaluronan (M(r) > 10(6) Da)
      than growth-inhibited cells in intact monolayers and up to 85% was targeted to
      the apical compartment, which was accompanied by increased HAS2 mRNA expression
      and slightly decreased HAS3 mRNA, while HAS1 mRNA remained undetectable.
      Hyaluronan and CD44 were exclusively expressed at the apical surface of
      proliferating/regenerating cells. After (re)establishment of tight junctions,
      hyaluronan was no longer detectable while CD44 was targeted to basolateral
      membrane domains. In vivo in inflamed human kidneys hyaluronan was abundantly
      expressed in the cortical tubulointerstitial space as well as at the luminal
      surface of regenerating renal tubular cells. CONCLUSION: These results
      demonstrate that the production of hyaluronan by renal tubular cells is activated
      during proliferation and in response to mechanical injury and that hyaluronan and
      CD44 expression is highly polarized. The targeted delivery of hyaluronan to the
      apical compartment suggests that hyaluronan produced by renal tubular cells
      supports proliferation/regeneration in the renal tubules, but that it does not
      contribute to hyaluronan accumulation in the renal interstitium. These data
      further support the concept that mitogen/stress-induced hyaluronan deposition in
      the renal tubules increases the risk for crystal retention and stone formation.

PMID- 15954898
TI  - Citrullination preferentially proceeds in glomerular Bowman's capsule and
      increases in obstructive nephropathy.
AB  - BACKGROUND: Peptidylarginine deiminases (PADs) are a group of posttranslational
      modification enzymes that citrullinate (deiminate) protein arginine residues,
      yielding citrulline residues. Citrullination of arginine residues abolishes their
      positive charge, markedly altering their structure. We undertook this study to
      investigate the actions of PADs in the kidney. METHODS: In male rats, we ligated
      the unilateral ureter, then analyzed the obstructed and contralateral kidneys 1
      week later. Controls were rats simultaneously given sham operations. In another
      experiment, we ligated unilateral ureters of eight rats, four of which received a
      ureter-bladder anastomosis 1 week later. These rats were subjected to histologic
      examinations 5 weeks after unilateral ureteral obstruction (UUO). RESULTS:
      Reverse transcription-polymerase chain reaction (RT-PCR) revealed that, of PADs
      (type I, II, III, and IV), only PAD type II was expressed in kidneys. Western
      blot study showed that PAD type II expression and citrullinated protein content
      increased greatly in kidneys that underwent unilateral ureteral ligation compared
      to that in contralateral or sham-operated kidneys. Immunohistochemical analyses
      revealed that PAD type II was preferentially expressed by parietal epithelial
      cells and that only in Bowman's capsule were proteins citrullinated.
      Additionally, these PAD type II and citrullinated proteins in obstructed
      nephropathy were significantly attenuated by the release of the obstruction.
      Proteome analysis revealed that one of citrullinated proteins in the kidney
      should be actin. CONCLUSION: This result indicates that PAD type II and
      citrullinated proteins are suitable markers of Bowman's capsule. Not only are
      these markers preferentially expressed in Bowman's capsules but their expression
      is also increased in damaged kidneys by UUO, features that promise the further
      clarification of kidney diseases.

PMID- 15954899
TI  - The antifibrotic effects of relaxin in human renal fibroblasts are mediated in
      part by inhibition of the Smad2 pathway.
AB  - BACKGROUND: The peptide hormone relaxin has been demonstrated to exert
      antifibrotic effects in renal and extrarenal tissues. The aims of this study were
      to identify potential anti-fibrotic effects of relaxin on human renal fibroblasts
      in vitro and to analyze their mechanisms. METHODS: All experiments were performed
      in established renal fibroblast cell lines and in primary cortical fibroblasts.
      Effects of relaxin were analyzed on cell proliferation, apoptosis, activation of
      renal fibroblasts, synthesis and secretion of collagen type I and fibronectin, as
      well as on the secretion of matrix metalloproteinases (MMPs). Effects on
      transforming growth factor-beta1 (TGF-beta1) receptor binding were analyzed by
      flow cytometry and on TGF-beta1 signal transduction by immunoblot analyses for
      Smad4 and 7, translocation from cytosol to nucleus for Smad2 and 3 as well as for
      phosphorylated and unphosphorylated forms of p38, c-Jun NH2 terminal kinase (JNK)
      and extracellular-regulated protein kinase (ERK). Finally, specific siRNAs for
      Smad2 and 3 were applied to assess the signal transduction pathway. RESULTS:
      After stimulation with relaxin, tyrosine phosphorylation of a 220 kD protein was
      demonstrated, indicating interaction with the receptor. Relaxin had only modest
      inhibitory effects on cell proliferation, and no effects on apoptosis.
      Conversely, relaxin exerted robust effects on TGF-beta1-induced fibroblast to
      myofibroblast transformation as well as on matrix synthesis and secretion even at
      the smallest dose tested. The secretion of MMP-2 and MMP-9 was induced noticeably
      by all investigated relaxin concentrations. TGF-beta1 receptor binding was not
      influenced by relaxin; however, it prevented Smad2 phosphorylation, translocation
      to nucleus, and complex formation between Smad2 and 3 indicating a possible
      interaction with TGF-beta1 signaling. These findings were corroborated by studies
      using siRNAs to Smad2 and 3 where siRNA to Smad2 but not to Smad3 inhibited the
      TGF-beta1 induction of fibronectin synthesis. There was no influence of relaxin
      on intracellular Smad3, Smad4, and Smad7 translocation or phosphorylation of
      mitogen-activated protein (MAP) kinases. CONCLUSION: Relaxin is a potent
      inhibitor of TGF-beta1-induced extracellular matrix (ECM) synthesis and secretion
      as well as fibroblast activation. Furthermore, it induces ECM degradation by
      induction of MMP-2 and MMP-9. These effects are mediated, at least in part, by
      inhibition of TGF-beta1 signaling.

PMID- 15954900
TI  - Shedding of endothelial protein C receptor contributes to vasculopathy and renal
      injury in lupus: in vivo and in vitro evidence.
AB  - BACKGROUND: Candidate biomarkers for vasculopathy in systemic lupus erythematosus
      (SLE) include circulating endothelial cells and the recently identified
      endothelial protein C receptor (EPCR) which, when shed, promotes a thrombotic
      diathesis. This study sought correlation between plasma levels of soluble EPCR
      and disease manifestation/severity, with a focus on lupus nephritis. METHODS: In
      81 SLE patients (evaluated cross-sectionally and longitudinally) and 59 healthy
      controls, levels of soluble EPCR and soluble E-selectin were assessed by sandwich
      enzyme-linked immunosorbent assay (ELISA), circulating endothelial cells isolated
      by immunomagnetic separation, and EPCR gene polymorphisms determined. Mechanisms
      of vascular injury were addressed in vitro in human aortic endothelial cells
      (HAEC) cultured in the presence and absence of interferon-gamma (IFN-gamma).
      RESULTS: The mean level of soluble EPCR was significantly higher in SLE patients
      (263 +/- 13 ng/mL) than controls (174 +/- 11 ng/mL) (P < 0.0001). Patients with
      active or past renal involvement had significantly higher mean soluble EPCR
      levels (306 +/- 21 ng/mL) (N= 40) than patients without nephritis (228 +/- 14
      ng/mL) (N= 41) (P= 0.0033). Mean soluble EPCR correlated positively with serum
      creatinine (R= 0.3429, P < 0.0001). The prevalence of the enhanced-shedding EPCR
      polymorphism A6936G was higher in SLE (41%) (N= 27) than controls (7%) (N= 29)
      (P= 0.0039). Patient and control plasma were also interrogated for soluble E
      selectin, a comparator plasma marker. The results suggest that soluble E-selectin
      and soluble EPCR are not equivalent end points of vasculopathy and endothelial
      perturbation in SLE. Although in SLE patients the absence or diminished
      expression of membrane EPCR on circulating endothelial cells varied, the rare
      circulating endothelial cells detected in controls invariably expressed membrane
      bound EPCR. IFN-gamma-treated HAEC expressed less membrane-bound EPCR [133
      relative fluorescence units (rfu)] than untreated HAEC (275 rfu); more soluble
      EPCR was detected in IFN-gamma-treated (1.1 ng/10(6) cells) than untreated HAEC
      (0.65 ng/10(6) cells) (P= 0.027). CONCLUSION: The results obtained from this
      cross-sectional/longitudinal study support the hypothesis that the vascular
      dysfunction characteristic of SLE may be related to a dramatically altered
      distribution of EPCR, both soluble and membrane-bound forms.

PMID- 15954901
TI  - Kidneys with heavy proteinuria show fibrosis, inflammation, and oxidative stress,
      but no tubular phenotypic change.
AB  - BACKGROUND: Sustained proteinuria is a major factor leading to kidney fibrosis
      and end-stage renal failure. Tubular epithelial cells are believed to play a
      crucial role in this process by producing mediators leading to fibrosis and
      inflammation. Congenital nephrotic syndrome of the Finnish type (NPHS1) is a
      genetic disease caused by mutations in a podocyte protein nephrin, which leads to
      constant heavy proteinuria from birth. In this work we studied the
      tubulointerstitial changes that occur in NPHS1 kidneys during infancy. METHODS:
      The pathologic lesions and expression of profibrotic and proinflammatory factors
      in nephrectomized NPHS1 kidneys were studied by immunohistochemistry, Western
      blotting, and cytokine antibody array. Oxidative stress in kidneys was assessed
      by measurement of gluthatione redox state. RESULTS: The results indicated that
      (1) severe tubulointerstitial lesions developed in NPHS1 kidneys during infancy;
      (2) tubular epithelial cells did not show transition into myofibroblasts as
      studied by the expression of vimentin, alpha-smooth muscle actin (alpha-SMA),
      collagen, and matrix metalloproteinases 2 and 9 (MMP-2 and -9); (3) the most
      abundant chemokines in NPHS1 tissue were neutrophil activating protein-2 (NAP-2),
      macrophage inhibiting factor (MIF), and monocyte chemoattractant protein-1 (MCP
      1); (4) monocyte/macrophage cells expressing CD14 antigen were the major
      inflammatory cells invading the interstitium; (5) the arteries and arterioles
      showed intimal hypertrophy, but the microvasculature in NPHS1 kidneys remained
      quite normal; and (6) excessive oxidative stress was evident in NPHS1 kidneys.
      CONCLUSION: Heavy proteinuria in NPHS1 kidneys was associated with interstitial
      fibrosis, inflammation, and oxidative stress. The tubular epithelial cells,
      however, were resistant to proteinuria and did not show epithelial-mesenchymal
      transition.

PMID- 15954902
TI  - ATRA induces podocyte differentiation and alters nephrin and podocin expression
      in vitro and in vivo.
AB  - BACKGROUND: Podocytes are terminally differentiated and highly specialized
      epithelial cells. The factors governing podocyte differentiation are poorly
      understood. We tested the hypothesis that all-trans retinoic acid (ATRA), a
      vitamin A derivative, induces podocyte differentiation in vitro and in vivo.
      METHODS: We tested the effects of ATRA on podocytes. Primary rat, primary mouse,
      and immortalized mouse podocytes were exposed to ATRA (1, 5, 10, 20, 40, 50, 80,
      160, and 200 micromol/L) or control (ethanol) for 72 hours. Cell morphology was
      examined by electron microscopy, the expression of podocyte specific proteins was
      measured by immunoflourescence and Western blot analysis, cell number and
      apoptosis were measured by 3-[4,5] dimethylthiazol-2,5-diphenyltetrazolium
      bromide (MTT) assay and Hoechst staining, respectively. To determine if ATRA
      alters podocyte differentiation in vivo, experimental injury was induced in
      C57BL6 mice using the antiglomerular antibody. Animals were given either daily
      intraperitoneal ATRA (16 mg/kg) or vehicle (corn oil). For end points, we
      measured proteinuria, podocyte-specific protein immunostaining, and proliferation
      [proliferating cell nuclear antigen (PCNA)] at days 5 and 14 (N= 5/group/time
      point). RESULTS: ATRA induced podocyte process formation in vitro, and
      significantly increased the expression of nephrin and podocin. This coincided
      with a reduction in proliferation. ATRA also significantly prevented the decrease
      in staining for synaptopodin, nephrin, and podocin in experimental animals (P <
      0.05 vs. control). This was accompanied by reduced proteinuria and decreased
      podocyte proliferation (P < 0.05 vs. control). CONCLUSION: ATRA induces podocyte
      differentiation in vitro and in vivo and alters the expression of certain
      podocyte-specific proteins. Further studies are ongoing to delineate the
      mechanism of this effect.

PMID- 15954903
TI  - Apatite plaque particles in inner medulla of kidneys of calcium oxalate stone
      formers: osteopontin localization.
AB  - BACKGROUND: We have previously shown that interstitial plaque particles appear
      first in the basement membranes of thin loops of Henle and then in the
      interstitial space. However, it is not known if the plaque in the basement
      membrane of thin loops of Henle is of the same or different form than the
      interstitial plaque. Thus our purpose here is to detail the structure of the
      interstitial and membrane-bound plaque and explore the relationship of plaque
      apatite to osteopontin, a well-known crystal-associated urine protein. METHODS:
      Deep papillary biopsy tissue was studied from all 15 calcium oxalate stone
      formers and four nonforming subjects that we previously reported on [Evan et al,
      J Clin Ivest, 2003]. Routine light and transmission electron microscopy (TEM) as
      well as light microscopy and TEM immunohistochemical localization of osteopontin
      antibody were performed on all 19 subjects. RESULTS: In the basement membrane,
      plaque particles are individual and appear laminated with alternating light
      regions of crystal and electron-dense organic layers. In the interstitium,
      individual particles are not abundant but are instead aggregated to form regions
      of attached particles and in some regions what appears to be a fusion or
      syncytium in which crystal islands float in an organic sea. By light microscopy
      immunohistochemistry, osteopontin was localized to cells of the loops of Henle
      and collecting ducts as well as on sites of plaque. By immunoelectron microscopy,
      osteopontin immunogold label was found mainly on the surfaces of apatite crystal
      phase, at the junction of the crystal/organic layers. A similar immunogold
      labeling pattern was seen in the particles forming the syncytial islands of
      interstitial plaque. CONCLUSION: If indeed we accept the hypothesis that apatite
      plaque may be an anchored site on which calcium oxalate stones form and grow, the
      present work makes clear that it is unlikely that the surface of plaque presented
      to the final urine will be apatite crystal per se. However, our findings clearly
      show osteopontin is one of the crystal-associated urine proteins involved in the
      formation of the organic layers of the plaque particles.

PMID- 15954904
TI  - Renal expression of SIBLING proteins and their partner matrix metalloproteinases
      (MMPs).
AB  - BACKGROUND: Three members of the small integrin-binding ligand N-linked
      glycoprotein (SIBLING) family of proteins have recently been shown to bind and
      activate specific promatrix metalloproteinases (MMPs) and to overcome the
      inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with
      mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when
      known, are coexpressed in salivary gland ductal cells. The present study examined
      the expression patterns of both the SIBLINGs and their MMP partners in adult
      kidney. METHODS: The expression patterns of all five SIBLINGs known to date, and
      their MMP partners were determined in monkey kidney using immunohistochemistry
      and in situ hybridization techniques. RESULTS: Bone sialoprotein (BSP) and its
      partner, MMP-2, were coexpressed in both the proximal and distal tubules.
      Osteopontin, as previously shown, was expressed in the distal tubules while its
      partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin
      matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron,
      including both parietal cells of Bowman's capsule and the thin limb of the loop
      of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular
      phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal
      tubule, and proximal tubule, respectively. CONCLUSION: In contrast to salivary
      gland in which all SIBLINGs and their MMP partners were coexpressed throughout
      the length of the ducts, these proteins were differentially expressed within the
      normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in
      the normal turnover of cell surface proteins and/or pericellular matrix proteins
      such as those in basement membranes.

PMID- 15954905
TI  - Aberrantly glycosylated serum IgA1 are closely associated with pathologic
      phenotypes of IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is the most common glomerulonephritis with
      various histologic and clinical phenotypes. The mechanisms underlying the
      pathogenesis of IgAN remained unclear. But now altered O-glycosylation of serum
      IgA1 observed in these patients was considered to be a key contributory factor.
      The aim of the current study is to investigate whether aberrantly glycosylated
      IgA1 was associated with pathologic phenotypes of IgAN. METHODS: Sera from 107
      patients with IgAN recently diagnosed were collected. Fifty patients were with
      mild mesangial proliferative IgAN, the others were with focal proliferative and
      sclerosing IgAN. Sera from 22 normal blood donors were used as normal controls.
      Biotinylated lectins were used in enzyme-linked immunosorbent assay (ELISA) to
      examine different glycans on IgA1 molecules. The alpha2,6 sialic acid was
      detected by elderberry bark lectin (SNA), the exposure of terminal galactose
      (Gal) and N-acetylgalactosamine (GalNAc) were detected by arachis hypogaea
      [peanut agglutinin (PNA)] and vilsa villosa lectin (VVL), respectively. The serum
      IgA1 glycans levels corrected by serum IgA1 concentrations were compared between
      patients and controls. RESULTS: Reduced terminal alpha2,6 sialic acid (1.16 +/-
      0.21 vs. 0.98 +/- 0.31) (P= 0.008) and galactosylation (0.30 +/- 0.29 vs. 0.16 +/
      0.19) (P= 0.029) increased exposure of (GalNAc) (0.00 vs. 0.03) (P= 0.024) were
      demonstrated in serum IgA1 from patients with IgAN as compared with those in
      controls. More important, the exposures of 2,6 sialic acid and Gal were
      significantly decreased, especially in patients with focal proliferative and
      sclerosing IgAN compared with that in patients with mild mesangial proliferative
      IgAN (0.91 +/- 0.34 vs. 1.05 +/- 0.25) (P= 0.014) (0.108 +/- 0.137 vs. 0.221 +/-
      0.219) (P= 0.018). However, no significant difference was found between patients
      with mild mesangial proliferative IgAN and normal controls (P > 0.05). The
      exposure of GalNAc of serum IgA1 from patients with focal proliferative and
      sclerosing IgAN was significantly higher than that of controls (P= 0.017), but
      had no statistical difference with that of patients with mild mesangial
      proliferative IgAN. CONCLUSION: The desialylation and degalactosylation of IgA1
      in sera of patients with IgAN were closely associated with pathologic phenotypes.

PMID- 15954906
TI  - Carbamylated low-density lipoprotein induces death of endothelial cells: a link
      to atherosclerosis in patients with kidney disease.
AB  - BACKGROUND: The presence of accelerated atherosclerosis in patients with kidney
      disease cannot be entirely explained by traditional cardiovascular risk factors.
      Exposure to urea, which is normally present in human blood plasma and elevated in
      patients with kidney disease, leads to the carbamylation of proteins. We
      postulated that low-density lipoprotein (LDL) carbamylated by urea has biologic
      effects relevant to atherosclerosis. METHODS: To produce carbamylated LDL (cLDL),
      human native LDL (nLDL) was chemically modified in vitro by exposure to potassium
      cyanate. Human coronary artery endothelial cells (HCAECs) and human coronary
      artery smooth muscle cells (CASMCs) were treated in vitro with cLDL or nLDL.
      Irreversible cell death was measured using the lactate dehydrogenase (LDH) assay,
      apoptosis was assessed by annexin V binding, and proliferation was determined
      using bromodeoxyuridine (BrdU) incorporation. Total plasma protein carbamylation
      and plasma cLDL were measured in hemodialysis patients using the homocitrulline
      assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: Our studies
      demonstrated that cLDL but not nLDL induced dose-dependent vascular cell injuries
      relevant to atherosclerosis, which included the proliferation of vascular smooth
      muscle cells and endothelial cell death. Under light microscopy, endothelial
      cells treated with cLDL showed signs of morphologic alterations. The injury to
      endothelial cells measured by LDH release was time-dependent and correlated with
      the degree of LDL carbamylation. At least a part of the endothelial cell
      population treated with cLDL died by apoptosis. In patients with advanced renal
      disease on hemodialysis, total plasma protein carbamylation and plasma cLDL were
      several times higher than in control healthy individuals. CONCLUSION:
      Collectively these data suggest the potential role of carbamylated LDL in
      accelerated atherosclerosis in patients with chronic renal disease and, possibly,
      in healthy individuals.

PMID- 15954907
TI  - Antihypertensive response to prolonged tempol in the spontaneously hypertensive
      rat.
AB  - INTRODUCTION: Tempol is a permeant nitroxide superoxide dismutase (SOD) mimetic
      that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats
      (SHRs). We investigated the hypothesis that the antihypertensive response entails
      a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1
      (ET-1), or catecholamines or correction of oxidative stress as indexed by 8
      isoprostane prostaglandin F(2alpha) (PGF(2alpha)) (8-Iso). METHODS: Groups (N= 6
      to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min)
      or given tempol (2 mmol/L) in drinking water. RESULTS: Tempol infusion reduced
      the MAP of anesthetized SHRs (150 +/- 5 vs. 126 +/- 6 mm Hg) (P < 0.005). Oral
      tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23
      +/- 6 mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion
      increased the PRA (2.2 +/- 0.2 vs. 5.0 +/- 0.9 ng/mL/hour) (P < 0.005), did not
      change excretion of nitric oxide (NO) [NO(2)+ NO(3) (NOx)], ET-1, or
      catecholamines but reduced excretion of 8-Iso (13.2 +/- 1.4 vs. 9.6 +/- 0.9 ng/24
      hours; P < 0.01). Cumulative Na(+) balance and gain in body weight were unaltered
      by tempol infusion. Tempol prevented a rise in MAP with high salt intake.
      CONCLUSION: Tempol corrects hypertension without a compensatory sympathoadrenal
      activation or salt retention. The response is independent of nitric oxide,
      endothelin, or catecholamines and occurs despite increased PRA. It is accompanied
      by a reduction in oxidative stress and is maintained during increased salt
      intake.

PMID- 15954908
TI  - A novel type of encephalopathy associated with mushroom Sugihiratake ingestion in
      patients with chronic kidney diseases.
AB  - BACKGROUND: The etiology of encephalopathy in uremic patients is multiple. We
      recently encountered a novel type of encephalopathy which occurred exclusively in
      patients with chronic kidney diseases after ingestion of a mushroom called
      Sugihiratake. While the exact etiology of this encephalopathy remained
      mysterious, we aimed to describe its clinical features. METHODS: A total of 32
      patients with chronic kidney diseases who had presented with encephalopathy
      following ingestion of Sugihiratake were enrolled from seven prefectures in
      Japan., with 24 of the 32 patients undergoing regular hemodialysis. The patient's
      clinical data were from surveillance by The Japanese Society of Nephrology.
      RESULTS: There was a significant association between Sugihiratake ingestion and
      the occurrence of encephalopathy in 524 hemodialysis patients questioned for a
      recent ingestion of this mushroom (P= 0.0006). The latent asymptomatic period
      before the onset of symptoms varied from 1 to 31 days (mean 9.1 +/- 7.3) days.
      The patient's symptoms consisted of disturbed consciousness in 30 patients
      (93.8%), convulsions in 25 (78.1%), myoclonus in 15 (46.9%), dysarthria in ten
      (31.3%), ataxia in eight (25.0%), paresis or paralysis in seven (21.9%), and skin
      parasthesia in two patients (6.3%). Nine (27.2%) patients died, mostly due to
      respiratory failure. The other patients were either discharged or still in
      hospitals with various degrees of clinical improvement. CONCLUSION: Patients with
      chronic kidney diseases are at risk of having serious encephalopathy following
      Sugihiratake ingestion and must refrain from eating it. Physicians, in those
      parts of the world, where this mushroom harvesting is common, should be aware of
      this complication.

PMID- 15954909
TI  - Impact of diabetic nephropathy and angiotensin II receptor blockade on urinary
      polypeptide patterns.
AB  - BACKGROUND: New insights into the pathogenesis and treatment of diabetic renal
      disease may emerge from recent advances in proteomics using high-throughput mass
      spectrometry (MS) of urine. METHODS: Using a combination of online capillary
      electrophoresis (CE) and MS we evaluated urinary polypeptide patterns in four
      groups of type 2 diabetic patients matched for age, gender, and diabetes
      duration, including 20 normoalbuminuric patients with and 20 without diabetic
      retinopathy, 20 microalbuminuric patients with diabetic retinopathy, and 18
      macroalbuminuric patients with diabetic retinopathy. Furthermore, changes in
      urinary polypeptide patterns during treatment with the angiotensin II receptor
      blocker (ARB) candesartan were evaluated in the macroalbuminuric patients in a
      randomized double-blinded, cross-over trial where each patient received treatment
      with placebo, candesartan 8, 16, and 32 mg daily each for 2 months. RESULTS:
      Overall, 4551 different polypeptides were found in the samples. Urinary
      polypeptide patterns were comparable in normo- (with and without diabetic
      retinopathy) and microalbuminuric patients, whereas distinct differences were
      found in macroalbuminuric patients. Differences in urinary polypeptide patterns
      between normo- and macroalbuminuric patients permitted the establishment of a
      "diabetic renal damage" pattern consisting of 113 polypeptides. Eleven of these
      polypeptides had been sequenced and identified. Candesartan treatment in
      macroalbuminuric patients significantly changed 15 of the 113 polypeptides in the
      diabetic renal damage pattern toward levels in normoalbuminuric patients. Change
      in the diabetic renal damage pattern was not candesartan dose-dependent but
      individual changes correlated with changes in urinary albumin excretion at each
      dose level. CONCLUSION: CE-MS serves as a fast and sensitive tool for
      identification of biomarkers and urinary polypeptide patterns specific for
      macroalbuminuric type 2 diabetic patients and may be used to explore and monitor
      renoprotective effects of ARB.

PMID- 15954910
TI  - Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant
      polycystic kidney disease.
AB  - BACKGROUND: The fluid filling renal cysts in human polycystic kidneys is secreted
      chiefly by the tubular epithelium lining the cysts via secondary chloride
      transport. Inhibiting this process by somatostatin therapy should induce
      shrinking of renal cysts. METHODS: In this randomized, cross-over, placebo
      controlled trial we compared the risk/benefit profile of 6-month treatment with
      long-acting somatostatin (octreotide-LAR, 40 mg intramuscularly every 28 days) or
      placebo in autosomal-dominant polycystic kidney disease (ADPKD) patients with
      mild-to-moderate renal insufficiency and no evidence of other kidney disease.
      Volumes of kidney structures were evaluated by a two-slice computed tomography
      (CT) scanner; while glomerular filtration rate (GFR) was estimated by iohexol
      plasma clearance. RESULTS: One patient on somatostatin and one on placebo were
      prematurely withdrawn because of nonsymptomatic, reversible colelithiasis and
      asthenia, respectively. In the remaining 12 patients somatostatin was well
      tolerated. Kidney volume increased by 71 +/- 107 mL (P < 0.05) on somatostatin
      and by 162 +/- 114 mL (P < 0.01) on placebo. The percent increase was
      significantly lower on somatostatin (2.2 +/- 3.7% vs. 5.9 +/- 5.4%) (P < 0.05).
      Cystic volume tended to increase less on somatostatin than on placebo (3.0 +/-
      6.5% vs. 5.6 +/- 5.8%). The "parenchymal" volume nonsignificantly increased by
      2.5 +/- 8.4% on placebo and slightly decreased by 4.4 +/- 8.9% on somatostatin.
      The GFR did not change significantly during both treatment periods. CONCLUSION:
      In ADPKD patients, 6-month somatostatin therapy is safe and may slow renal volume
      expansion. This may reflect an inhibited growth in particular of smallest cysts
      beyond the detection threshold of CT scan evaluation. Whether this effect may
      prove renoprotective in the long term should be tested in additional trials of
      longer duration.

PMID- 15954911
TI  - C-reactive protein as predictor of death in end-stage diabetic nephropathy: role
      of peripheral arterial disease.
AB  - BACKGROUND: Patients with diabetes type 2 receiving dialysis therapy have a poor
      survival prognosis, mainly due to cardiovascular events. Increased C-reactive
      protein (CRP) levels, important in atherosclerosis, are associated with an
      increased risk for cardiovascular events. However, to date no study has shown the
      predictive value of CRP in relation to peripheral arterial disease stage.
      METHODS: We enrolled all 445 prevalent patients with diabetic nephropathy
      receiving maintenance hemodialysis in 30 centers in Southern Germany from August
      1999 to January 2000 for prospective study until December 2003. At inclusion, CRP
      and a complete clinical phenotype, including peripheral arterial disease Fontaine
      Stage were determined. The primary end point was all-cause mortality. RESULTS: A
      total of 305 (68.5%) patients died. An increased log CRP at study inclusion was
      significantly associated with an increase in hazard ratio (HR) by multivariate
      Cox regression for all-cause (HR = 1.5, P= 0.002) and cardiac death (HR = 1.76,
      P= 0.02) in the entire collective. This result was applicable only to patients
      with peripheral arterial disease Fontaine stage IV (N= 190, multivariate HR =
      1.75 for all-cause mortality, P= 0.006). Possibly due to inadequate power, we
      observed only an insignificant trend for CRP as predictor of all-cause death in
      patients without peripheral arterial disease or with less severe forms of
      peripheral arterial disease (HR = 1.36, P= 0.08). CONCLUSION: In contrast to
      patients with peripheral arterial disease stage IV, patients with less severe
      atherosclerosis and elevated CRP are, if any, at less risk for cardiovascular
      mortality, possibly due to the difference in extent of affected vasculature and
      thus activated platelets and coagulation. Before judging the predictive value of
      CRP for mortality, peripheral vessel status should be determined.

PMID- 15954912
TI  - Chronic kidney disease and cardiovascular disease in a general Japanese
      population: the Hisayama Study.
AB  - BACKGROUND: Chronic kidney disease has been shown to be an independent risk
      factor for cardiovascular disease in high-risk populations. However, this
      relationship is inconclusive in community-based populations. METHODS: To clarify
      this issue, we followed 2634 community-dwelling individuals without
      cardiovascular disease, aged 40 years or older, for 12 years and examined the
      relationship between chronic kidney disease and the incidence of cardiovascular
      disease. RESULTS: During the follow-up period, 99 subjects (56 men and 43 women)
      experienced coronary heart disease, 137 subjects (60 men and 77 women) ischemic
      stroke, and 60 subjects (26 men and 34 women) hemorrhagic stroke. In men, the age
      adjusted incidence of coronary heart disease was significantly higher in subjects
      with chronic kidney disease than in those without it (6.2 vs. 2.9 per 1000 person
      years) (P < 0.05), but such a relationship was not observed with ischemic stroke.
      In contrast, in women, the age-adjusted incidence of ischemic stroke was
      significantly higher in subjects with chronic kidney disease than in those
      without it (3.4 vs. 2.5) (P < 0.05), while that of coronary heart disease was
      not. Chronic kidney disease was not found to be associated with the incidence of
      hemorrhagic stroke. In multivariate analysis, even after adjustments for
      traditional and nontraditional cardiovascular disease risk factors, chronic
      kidney disease was found to be an independent risk factor for the occurrence of
      coronary heart disease in men [hazard ratio (HR), 2.26; 95% CI, 1.06-4.79], and
      for the occurrence of ischemic stroke in women (HR, 1.91; 95% CI, 1.15-3.15).
      CONCLUSION: Our findings suggest that chronic kidney disease is an independent
      risk factor for the occurrence of cardiovascular disease in the general Japanese
      population.

PMID- 15954913
TI  - Biomarkers of inflammation and progression of chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease is associated with higher levels of
      inflammatory biomarkers. Statins have anti-inflammatory properties and may
      attenuate loss of kidney function. Although inflammation may mediate progressive
      renal injury, the relation between statin use, markers of inflammation, and the
      rate of kidney function loss has not been elucidated. We examined the association
      between pravastatin use, levels of C-reactive protein (CRP), soluble tumor
      necrosis factor receptor II (sTNFrii), and the rate of kidney function loss.
      METHODS: We performed a post hoc analysis of data from a randomized placebo
      controlled trial of pravastatin 40 mg daily in people with previous myocardial
      infarction. Glomerular filtration rate (GFR) was estimated using the Modification
      of Diet in Renal Disease Study (MDRD) GFR equation. We studied 687 subjects with
      chronic kidney disease (GFR < 60 mL/min/1.73 m(2)) who did not experience a
      cardiovascular event during follow-up. Multivariate linear regression was used to
      study the relation between baseline CRP and sTNFrii and the rate of kidney
      function loss in mL/min/1.73 m(2)/year. Cross-product interaction terms were used
      to determine if these relations varied with pravastatin use. RESULTS: Median
      baseline GFR was 54.5 mL/min/1.73 m(2) (interquartile range 49.7, 57.8) and
      median duration of follow-up was 58 months. Higher baseline CRP level was
      independently associated with more rapid kidney function loss (highest tertile
      0.6 mL/min/1.73 m(2) per year faster than lowest tertile) (P= 0.001). A similar
      independent relation was observed between tertile of sTNFrii and rate of kidney
      function loss (highest tertile 0.5 mL/min/1.73 m(2) per year faster than lowest
      tertile) (P= 0.006). Subjects with both CRP and sTNFrii in the highest tertile
      ("inflamed" status) appeared to derive more renal benefit from pravastatin than
      those without (P for interaction 0.047). In these 108 subjects, renal function
      loss in pravastatin recipients was 0.8 mL/min/1.73 m(2)/year slower than placebo
      (95% CI 0 to 1.5 mL/min/1.73 m(2)/year slower) (P= 0.039). CONCLUSION: Higher CRP
      and sTNFrii are independently associated with faster rates of kidney function
      loss in chronic kidney disease. Pravastatin appears to prevent loss of kidney
      function to a greater extent in individuals with greater evidence of
      inflammation, although this was of borderline significance. These data suggest
      that inflammation may mediate the loss of kidney function among subjects with
      chronic kidney disease and concomitant coronary disease.

PMID- 15954914
TI  - Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney
      disease: effect of long-term therapy with erythropoietin.
AB  - BACKGROUND: Erythrocytes represent an important component of the antioxidant
      capacity of blood, comprising, in particular, intracellular enzymes, including
      platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase
      (Gpx). We evaluated the erythrocyte PAF-AH and Gpx activities in various stages
      of chronic kidney disease (CKD), and further investigated whether erythropoietin
      (EPO) administration in these patients has any influence on the enzyme
      activities. METHODS: Thirty-six patients (19 men and 17 women) with CKD (stages 1
      to 5) participated in the study. Thirteen of them presented with CKD stage 1 to 2
      (group I), whereas 23 patients presented with CKD stage 3 to 5 and randomized
      into two groups (i.e., groups II and III). Patients of group II (N= 11) were
      administered EPO subcutaneously, 50 units per kg once per week. In group III (N=
      12), EPO was initiated only when the hemoglobin (Hb) levels decreased during
      follow-up to less than 9 g/dL. All patients were seen on an outpatient basis at 2
      and 4 months. Fifteen normolipidemic age- and sex-matched healthy volunteers also
      participated in the study and were used as controls. The PAF-AH and Gpx
      activities were determined in isolated washed erythrocytes. RESULTS: The
      erythrocyte-associated PAF-AH and Gpx activities were higher in all CKD patient
      groups at baseline compared to controls, the groups II and III exhibiting
      significantly higher enzyme activities compared with group I. In all studied
      populations, both enzyme activities were negatively correlated with the
      creatinine clearance values. Importantly, the PAF-AH and Gpx activities were
      progressively decreased during the follow-up in patients not treated with EPO
      (group III), a phenomenon not observed in patients receiving EPO (group II), or
      in patients of group I. This reduction in enzyme activities was positively
      correlated with the decrease in the creatinine clearance values in patients of
      group III. CONCLUSION: Significant alterations in the erythrocyte-associated PAF
      AH and Gpx activities related to the disease stage are observed in CKD patients.
      Administration of EPO prevented the reduction in enzyme activities observed
      during the progression of the renal insufficiency, thus preserving the
      erythrocyte defense mechanisms against oxidative stress.

PMID- 15954915
TI  - Identification of podocin (NPHS2) gene mutations in African Americans with
      nondiabetic end-stage renal disease.
AB  - BACKGROUND: Podocin, encoded by NPHS2 and mapped to 1q25.2, is an integral
      membrane protein exclusively expressed in glomerular podocytes. Mutations in the
      NPHS2 gene cause autosomal-recessive nephrotic syndrome and have been associated
      with proteinuria in several populations. Evidence for linkage of end-stage renal
      disease (ESRD) to chromosome 1q25-31 in the region of NPHS2 has been identified
      in a genome-wide scan in African American (AA) siblings. METHODS: To investigate
      the potential role of this gene in ESRD, we sequenced all coding regions and
      approximately 2 kb of upstream promoter sequence of NPHS2 in 96 unrelated AA
      nondiabetic ESRD cases and 96 healthy population-based AA controls, and assessed
      several single nucleotide polymorphisms (SNPs) for association in a larger case
      control sample. RESULTS: Fifty-five variants were identified with minor allele
      frequencies ranging from <1% to 44%. Twenty-three polymorphisms were located in
      the promoter region, 11 were exonic, 13 were intronic, and 8 were in the 5' and
      3'- untranslated regions. Two novel nonsynonymous coding SNPs were identified
      (A44E and A61V). An insertion polymorphism in intron 3, IVS3+9insA, was detected
      in 6 ESRD patients and in no controls. This variant, and 4 other common SNPs,
      were evaluated in a larger sample of 288 AA ESRD cases and 278 AA controls. The
      overall minor allele frequencies for the insertion allele were 0.018 in cases and
      0.002 in controls. Significant evidence of association of IVS3+9insA was observed
      (P= 0.012), and the haplotype containing the insertion allele in cases was also
      associated. CONCLUSION: These results suggest that uncommon variants of the NPHS2
      gene may play a role in the development of nondiabetic ESRD in AAs.

PMID- 15954916
TI  - Factors influencing the progression of renal damage in patients with unilateral
      renal agenesis and remnant kidney.
AB  - BACKGROUND: Although some studies have shown that the risk to develop proteinuria
      and renal insufficiency is increased in patients with a remnant kidney (RK) or
      unilateral renal agenesis (URA), other patients maintain normal renal function
      and negative proteinuria, and the reasons to explain these different outcomes are
      not known. METHODS: We performed a retrospective study of 54 patients with a
      severe reduction in renal mass (33 patients with URA and 21 with RK). Follow-up
      was 100 +/- 72 months. RESULTS: Twenty patients (group 1) showed normal renal
      function at presentation, whereas the 34 remaining (group 2) had proteinuria, and
      some of them renal insufficiency. Group 2 patients were older and had a higher
      blood pressure and BMI than group 1 patients. Eleven patients of group 1 remained
      normal throughout follow-up (group 1A), whereas the remaining 9 developed
      proteinuria/renal insufficiency (group 1B). BMI at presentation was significantly
      higher in group 1B: 27 +/- 3.6 kg/m(2) versus 21.6 +/- 2.6 kg/m(2), and BMI was
      the only factor statistically associated with the risk to develop
      proteinuria/renal insufficiency in group 1. Among group 2 patients, renal
      function remained stable in 20 (group 2A), and deteriorated (>50% increase of
      baseline serum creatinine) in the remaining 14 patients (group 2B). BMI at
      presentation and treatment with ACEI during follow-up were the only factors
      statistically associated with the risk for renal failure progression among group
      2 patients. CONCLUSION: Overweight plays a fundamental role in the appearance of
      proteinuria and renal damage in patients with severe renal mass reduction.

PMID- 15954917
TI  - Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney
      disease (CKD) due to type 2 diabetes.
AB  - BACKGROUND: Cardiovascular calcification (CVC) is common and severe in patients
      with end-stage renal disease on dialysis. However, the prevalence and severity of
      CVC is less well documented in patients with chronic kidney disease (CKD) not yet
      on dialysis. METHODS: Fifty-eight nondialyzed HA with type 2 diabetes and CKD
      were enrolled. They comprise 29 patients with stages 1 and 2 CKD (early CKD
      group) and 26 patients with stages 4 and 5 CKD (advanced CKD group). Coronary
      artery calcification (CAC) was measured by ultrafast spiral computed tomography,
      while peripheral artery calcification (PAC) was evaluated by plain x-ray of the
      chest, pelvis, thighs, and lower extremities. RESULTS: The prevalence of CAC and
      PAC were significantly higher in the advanced CKD group compared to the early CKD
      group (73% vs. 38%; P < 0.01 and 85% vs. 35%; P < 0.0001, respectively). The
      median CAC scores were 18-fold greater in the advanced CKD group (138.9 vs. 7.8,
      respectively). By linear regression analysis, a strong association was found
      between the level of renal function and ln total volume of CAC. CONCLUSION: Our
      data indicate that CAC and PAC are common and severe in HA diabetic patients with
      CKD not previously treated with dialysis, calcium-based phosphate binders, or
      vitamin D analogues. Lower level of renal function is associated with increased
      burden of vascular calcification in predialysis patients with CKD.

PMID- 15954918
TI  - Interleukin-1 gene cluster polymorphisms predict risk of ESRD.
AB  - BACKGROUND: Patients with chronic kidney disease manifest an inflammatory state
      relative to healthy individuals. Inflammation is regulated in part by genes of
      the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this
      gene cluster may be associated with risk of end-stage renal disease (ESRD).
      METHODS: Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239
      racially diverse hemodialysis (HD) patients and 252 controls. These individuals
      were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and
      beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1
      receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic
      regression for their independent associations with ESRD, and the effect of allele
      dose of IL-1RN on risk for ESRD was examined. The interaction between race and
      genotype was also investigated. RESULTS: A logistic regression model demonstrated
      that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats
      (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005).
      The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and
      of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated
      with ESRD, but this is accounted for by race (P= 0.04). CONCLUSION: Two
      polymorphisms within the IL-1 gene cluster are associated with ESRD independent
      of race. This finding is one of the strongest associations between genotype and
      ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect
      the risk of development of ESRD.

PMID- 15954919
TI  - A pilot randomized controlled trial of renal protection with pioglitazone in
      diabetic nephropathy.
AB  - BACKGROUND: Diabetic nephropathy progresses relentlessly to end-stage renal
      disease (ESRD). Animal experiments have found that peroxisome proliferator
      activated receptor-gamma (PPAR-gamma)-based therapy can have a glucose
      independent effect on renal protection. We hypothesized that PPAR-gamma-based
      antidiabetic therapy would result in greater reduction in proteinuria compared to
      sulfonylurea-based therapy. METHODS: In 44 patients with overt diabetic
      nephropathy, an open-label, blinded end point trial was conducted in which
      subjects were randomized to either pioglitazone or glipizide to achieve similar
      glucose control. Proteinuria was assessed by two collections of 24-hour urine
      samples each month for 4 months. RESULTS: The glipizide group had an adjusted
      mean increase in proteinuria of 6.1% (95% CI -11.7%, 23.8%), whereas the
      pioglitazone group had a reduction of 7.2% (95% CI -24.9%, 10.6%). The adjusted
      reduction with pioglitazone of 13.2% (95% CI -38.4%, 11.9%) was not statistically
      significant (P= 0.294). Baseline proteinuria, diastolic ambulatory blood
      pressure, and serum albumin concentration were independent predictors of
      reduction in proteinuria. The frequency and patterns of adverse events were
      similar in the two groups. CONCLUSION: In patients with advanced diabetic
      nephropathy, we found no reduction in proteinuria over 4 months. These data are
      useful to design larger studies with longer duration of follow-up to demonstrate
      renal protection of PPAR-gamma agonists.

PMID- 15954920
TI  - Atherosclerotic renovascular disease in United States patients aged 67 years or
      older: risk factors, revascularization, and prognosis.
AB  - BACKGROUND: Although atherosclerotic renovascular disease is increasingly
      recognized in chronic kidney disease, few national level studies have examined
      its clinical epidemiology. METHODS: Claims data from a 5% random sample of the
      United States Medicare population were used to select patients without
      atherosclerotic renovascular disease in the 2 years preceding December 31, 1999
      (N= 1,085,250), followed until December 31, 2001. RESULTS: The incidence of
      atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major
      antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5]
      included chronic kidney disease (adjusted HR 2.54), hypertension (2.42),
      peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70).
      Adverse event rates after incident atherosclerotic renovascular disease greatly
      exceeded those in the general population (P < 0.0001): atherosclerotic heart
      disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population);
      peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5
      (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs.
      52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3).
      Among atherosclerotic renovascular disease patients, 16.2% underwent a renal
      revascularization procedure, percutaneously in 96%. Revascularization was not
      associated with renal replacement therapy, congestive heart failure, or death but
      was associated with atherosclerotic heart disease (adjusted HR 1.42) (P= 0.004)
      and peripheral vascular disease (adjusted HR 1.38) (P= 0.002). CONCLUSION:
      Atherosclerotic renovascular disease is strongly associated with cardiovascular
      disease, both past and future. Absolute cardiovascular risk exceeds that of renal
      replacement therapy. Renal revascularization is used selectively and shows
      inconsistent associations with cardiovascular outcomes, renal replacement
      therapy, and death.

PMID- 15954921
TI  - Th2 cytokines increase and stimulate B cells to produce IgG4 in idiopathic
      membranous nephropathy.
AB  - BACKGROUND: The predominant deposition of IgG4 in idiopathic membranous
      nephropathy indicates that its presence characterizes the systemic immune
      response of the disease. METHODS: We analyzed the expressions of CD3, CD19, CD4,
      and CD8 on peripheral blood mononuclear cells (PBMCs) by flow cytometry, and the
      levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interferon (IFN)
      gamma, interleukin (IL)-4, IL-10, and IL-13 mRNAs in PBMCs using real-time
      reverse transcription-polymerase chain reaction (RT-PCR) in 14 patients with
      idiopathic membranous nephropathy and 14 normal control donors. The levels of IgG
      subclasses in the B-cell culture supernatant in the presence or absence of
      cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Idiopathic membranous nephropathy patients showed an increased CD4(+)/CD8(+)
      ratio, although the numbers of peripheral T and B cells were comparable to those
      of the normal control group. IL-10 and IL-13 mRNA expression levels increased in
      the idiopathic membranous nephropathy group. The levels of spontaneous production
      of each IgG subclass by B cells were identical in the two groups. In the presence
      of Th2 cytokines, B cells from several individuals of the idiopathic membranous
      nephropathy group augmented the production of IgG4. When the individual levels of
      each IgG subclass in the presence of cytokines were compared with those in the
      absence of cytokines in each sample, a significant increase in the production of
      IgG4 in the presence of IL-4 was observed in the idiopathic membranous
      nephropathy group. CONCLUSION: These results indicate that the altered functions
      of T cells to produce Th2 cytokines and the increased production of IgG4 by B
      cells in response to these cytokines characterize the immune response in
      idiopathic membranous nephropathy.

PMID- 15954922
TI  - Septicemia, access and cardiovascular disease in dialysis patients: the USRDS
      Wave 2 study.
AB  - BACKGROUND: Microinflammation is linked to cardiovascular disease, and is highly
      prevalent in dialysis patients. It is logical to postulate that septicemia, a
      common macroinflammatory occurrence in dialysis patients, contributes to their
      large burden of cardiovascular disease. METHODS: The Dialysis Morbidity and
      Mortality Wave 2 was a randomly selected prospective cohort of incident dialysis
      patients. Admission claims data were used to define and calculate rates of
      septicemia or bacteremia and cardiovascular events in those with Medicare as the
      primary payer. Utilizing Cox proportional hazard models we determined the
      association between baseline access and the development of bacteremia or sepsis,
      and also the association between bacteremia or sepsis episodes and subsequent
      cardiovascular events. RESULTS: The 2358 (59%) patients with Medicare as primary
      payer were older and more likely to have heart failure than those with other
      payers, but had similar comorbidity-adjusted mortality hazards. Rates of first
      septicemia, bacteremia, or either condition, were 7.0, 5.9 and 10.4 events per
      100-patient years, respectively. Cox regression identified initial dialysis
      access as the main antecedent of septicemia or bacteremia. Hazards ratios for
      hemodialysis with permanent catheters, temporary catheters, and grafts were 1.95
      (95% CI 1.47-2.57), 1.76 (95% CI 1.29-2.41), and 1.05 (95% CI 0.82-1.35),
      respectively, while that for peritoneal dialysis was 0.96 (95% CI 0.75-1.23)
      (reference arteriovenous fistula). After adjustment for baseline factors,
      septicemia or bacteremia, as a time-dependent covariate, was associated with
      subsequent death [hazards ratio (HR) 2.33, 95% CI 1.38-2.28], myocardial
      infarction (HR 1.78, 95% CI 1.38-2.28), heart failure (HR 1.64, 95% CI 1.39
      1.95), peripheral vascular disease (HR 1.64, 95% CI 1.34-2.0), and stroke (HR
      2.04, 95% CI 1.27-3.28). CONCLUSION: Septicemia appears to be an important,
      potentially preventable, cardiovascular risk factor in dialysis patients.

PMID- 15954923
TI  - Impact of initial dialysis modality and modality switches on Medicare
      expenditures of end-stage renal disease patients.
AB  - BACKGROUND: The number of end-stage renal disease (ESRD) enrollees and Medicare
      expenditures have increased dramatically. Pathways and associated Medicare
      expenditures in ESRD treatment need to be examined to potentially improve the
      efficiency of care. METHODS: This study examines the impact of initial dialysis
      modality choice and subsequent modality switches on Medicare expenditure in a 3
      year period. The Dialysis Morbidity and Mortality Study Wave 2 data by the United
      States Renal Data System (USRDS) is used along with the USRDS Core CD and USRDS
      claims data. RESULTS: A total of 3423 incident dialysis patients (approximately
      equal number of peritoneal dialysis and hemodialysis) were included in the
      analysis. Unadjusted average annual Medicare expenditure (in 2004 dollars) for
      peritoneal dialysis as first modality was 53,277 dollars(95% CI 50,626 dollars
      55,927 dollars), and 72,189 dollars (95% CI 67,513 dollars-76,865 dollars) for
      hemodialysis. Compared to "hemodialysis, no switch" subgroup, "peritoneal
      dialysis, no switch" had a significantly lower annual expenditure (44,111 dollars
      vs. 72,185 dollars) (P < 0.001). "Peritoneal dialysis, with at least one switch"
      and "hemodialysis, with at least one switch" had a lower or similar annual
      expenditure of 66,639 dollars and 72,335 dollars, respectively. After adjusting
      for patient characteristics, annual Medicare expenditure was still significantly
      lower for patients with peritoneal dialysis as the initial modality (56,807
      dollars vs. 68,253 dollars) (P < 0.001). Similarly, compared to "hemdialysis, no
      switch" subgroup, "peritoneal dialysis, no switch" and "peritoneal dialysis, with
      at least one switch" had a significantly lower total expenditure. Further
      analysis showed that time-to-first switch also independently impacted total
      expenditure. CONCLUSION: Initial modality choice (peritoneal dialysis or
      hemodialysis) and subsequent modality switches had significant implications for
      Medicare expenditure on ESRD treatments.

PMID- 15954924
TI  - Kidney transplantation and wait-listing rates from the international Dialysis
      Outcomes and Practice Patterns Study (DOPPS).
AB  - BACKGROUND: The international Dialysis Outcomes and Practice Patterns Study
      (DOPPS I and II) allows description of variations in kidney transplantation and
      wait-listing from nationally representative samples of 18- to 65-year-old
      hemodialysis patients. The present study examines the health status and
      socioeconomic characteristics of United States patients, the role of for-profit
      versus not-for-profit status of dialysis facilities, and the likelihood of
      transplant wait-listing and transplantation rates. METHODS: Analyses of
      transplantation rates were based on 5267 randomly selected DOPPS I patients in
      dialysis units in the United States, Europe, and Japan who received chronic
      hemodialysis therapy for at least 90 days in 2000. Left-truncated Cox regression
      was used to assess time to kidney transplantation. Logistic regression determined
      the odds of being transplant wait-listed for a cross-section of 1323 hemodialysis
      patients in the United States in 2000. Furthermore, kidney transplant wait
      listing was determined in 12 countries from cross-sectional samples of DOPPS II
      hemodialysis patients in 2002 to 2003 (N= 4274). RESULTS: Transplantation rates
      varied widely, from very low in Japan to 25-fold higher in the United States and
      75-fold higher in Spain (both P values <0.0001). Factors associated with higher
      rates of transplantation included younger age, nonblack race, less comorbidity,
      fewer years on dialysis, higher income, and higher education levels. The
      likelihood of being wait-listed showed wide variation internationally and by
      United States region but not by for-profit dialysis unit status within the United
      States. CONCLUSION: DOPPS I and II confirmed large variations in kidney
      transplantation rates by country, even after adjusting for differences in case
      mix. Facility size and, in the United States, profit status, were not associated
      with varying transplantation rates. International results consistently showed
      higher transplantation rates for younger, healthier, better-educated, and higher
      income patients.

PMID- 15954925
TI  - Nocturnal hemodialysis increases arterial baroreflex sensitivity and compliance
      and normalizes blood pressure of hypertensive patients with end-stage renal
      disease.
AB  - BACKGROUND: Impaired neural control of heart rate, elevated arterial stiffness,
      and hypertension place patients with end-stage renal disease (ESRD) at increased
      risk of cardiovascular mortality. Nocturnal hemodialysis (6 x 8 hours/week), a
      more intense program than conventional hemodialysis (3 x 4 hours/week), lowers
      blood pressure and restores brachial dilator responses to hyperemia and nitrates.
      METHODS: We hypothesized that nocturnal hemodialysis would increase arterial
      baroreflex sensitivity for heart rate of hypertensive ESRD patients by an
      afferent vascular mechanism. Ten consecutive hypertensive ESRD patients (age 42
      +/- 4) (mean +/- SEM) receiving conventional hemodialysis were studied before and
      2 months after conversion to nocturnal hemodialysis. Regression slopes relating
      RR interval responses to rises or falls in systolic blood pressure were averaged
      to derive spontaneous baroreflex sensitivity for heart rate for each patient, and
      the stroke volume/pulse pressure ratio was used to estimate total arterial
      compliance. RESULTS: Dialysis dose (Kt/V per session) increased from 1.2 +/- 0.05
      to 2.1 +/- 0.1 (P < 0.05). Despite withdrawal of antihypertensive medications
      (from 2.9 to 0.1 drugs/patient), nocturnal hemodialysis lowered systolic blood
      pressure (from 143 +/- 4 to 120 +/- 6 mm Hg) (P= 0.001). Both baroreflex
      sensitivity (from 4.76 +/- 1.1 msec/mm Hg to 6.91 +/- 1.1 msec/mm Hg) (P= 0.04)
      and total arterial compliance (from 0.98 +/- 0.13 mL/mm Hg to 1.43 +/- 0.2 mL/mm
      Hg) (P= 0.02) were higher following conversion to nocturnal hemodialysis.
      Increases in baroreflex sensitivity correlated with increases in stroke
      volume/pulse pressure (r= 0.845, P= 0.002). CONCLUSION: These findings are
      consistent with the concept that nocturnal hemodialysis increases baroreflex
      sensitivity via greater afferent baroreceptor responsiveness to pulsatile
      pressure. A more favorable risk profile, due to enhanced baroreflex regulation of
      the circulation and vascular compliance, may translate into lower cardiovascular
      event rates in ESRD patients receiving nocturnal hemodialysis.

PMID- 15954926
TI  - Modifiable factors predicting patient survival in elderly kidney transplant
      recipients.
AB  - BACKGROUND: Elderly transplant candidates represent an increasingly important
      group on the waiting list for kidney transplantation. Yet the factors that
      determine posttransplantation outcomes in this population remain poorly defined.
      METHODS: We performed a population-based retrospective cohort study involving all
      patients aged 60 years or older who received a first cadaveric kidney
      transplantation between 1985 and 2000 in the province of Quebec. The main
      outcomes were patient survival, overall graft survival, and treatment failure
      (patient death or graft loss within the first posttransplant year). Survival
      analyses were performed using a Cox proportional hazard model. Logistic
      regression identified factors predicting treatment failure. RESULTS: On
      multivariate analysis, the modifiable factors associated with patient survival
      were active smoking at transplantation [hazard ratio (HR) 2.09, 95% confidence
      interval (CI) 1.22-3.60)], body mass index (BMI) (HR 1.34 for a 5-point increase,
      95% CI 1.05-1.67), and time on dialysis before transplantation (HR 1.10 for a 1
      year increase, 95% CI 1.02-1.18). The only modifiable factor associated with
      graft survival was active smoking at transplantation (HR 2.04, 95% CI 1.24-3.30).
      Treatment failure was associated with time on dialysis before transplantation
      (odds ratio for dialysis >/=2 years 3.28, 95% CI 1.34-7.9). CONCLUSION: Our
      results show that active smoking, obesity, and time on dialysis before
      transplantation are modifiable risk factors associated with an increased risk of
      mortality after transplantation in elderly recipients. They represent potential
      targets for interventions aimed at improving patient and graft survival in
      elderly patients.

PMID- 15954927
TI  - Skeletal muscle mRNA for IGF-IEa, IGF-II, and IGF-I receptor is decreased in
      sedentary chronic hemodialysis patients.
AB  - BACKGROUND: Maintenance hemodialysis patients often display evidence for protein
      energy malnutrition, inflammation, and sarcopenia. We therefore investigated
      whether sedentary maintenance hemodialysis patients have decreased skeletal
      muscle mRNA levels and muscle and serum protein concentrations of certain growth
      factors. METHODS: Fifty-one clinically stable maintenance hemodialysis patients
      (32 men and 19 women), and 21 normal adults (16 men and five women) of similar
      age, gender mix, racial/ethnic backgrounds, serum albumin, body composition, and
      level of sedentary activity were studied. Individuals underwent biopsy of the
      right vastus lateralis muscle, and real-time polymerase chain reaction (PCR)
      amplification of mRNAs for insulin-like growth factor-I (IGF-I), IGF-II, IGF-I
      receptor (IGF-IR), IGF-IIR, and myostatin (44 patients) was performed. Serum and
      muscle IGF-I and IGF-II, serum proinflammatory cytokines, and leg muscle
      strength, power, and fatigability were measured. RESULTS: Maintenance
      hemodialysis patients displayed significantly reduced mRNA levels for IGF-IEa
      mRNA (P < 0.05), IGF-II (P < 0.001), and IGF-IR (P < 0.001), and no difference in
      mRNAs for IGF-IEc, IGF-IIR, or myostatin as compared to normal controls. Muscle
      mRNA levels, in general, followed the same pattern in male and female maintenance
      hemodialysis patients considered separately. In the maintenance hemodialysis
      patients, muscle IGF-I protein, serum IGF-II and tumor necrosis factor-alpha (TNF
      alpha) were each increased, whereas serum C-reactive protein (CRP) and
      interleukin-6 (IL-6) were normal. Muscle strength and power, but not
      fatigability, were reduced in the maintenance hemodialysis patients. CONCLUSION:
      In sedentary, clinically stable maintenance hemodialysis patients as compared to
      sedentary normal individuals, the mRNA levels for IGF-IEa, IGF-II, and the IGF-I
      receptor are decreased in vastus lateralis muscle. Protein levels for muscle IGF
      I and serum IGF-II are increased.

PMID- 15954928
TI  - Survival of liver transplant candidates with acute renal failure receiving renal
      replacement therapy.
AB  - BACKGROUND: Acute renal failure (ARF) in the setting of end-stage liver disease
      has a dismal prognosis without liver transplantation. Renal replacement therapy
      (RRT) is a common bridge to liver transplant despite a paucity of supportive
      data. We investigated our single-center patient population to determine efficacy
      of RRT in liver transplant candidates with ARF. METHODS: We identified 102 liver
      transplant candidates receiving RRT for ARF between April 30, 1999 and January
      31, 2004. Patients that had initiated RRT intra- or postoperatively or received
      outpatient hemodialysis or peritoneal dialysis prior to admission were excluded.
      Survival to liver transplant, short-term mortality following liver transplant,
      and selected clinical characteristics were examined. RESULTS: Of patients who
      received RRT, 35% survived to liver transplant or discharge. Mortality was 94% in
      patients not receiving a liver and was associated with a higher Acute
      Physiological and Chronic Health Evaluation (APACHE) II, lower mean arterial
      pressure, and the use of continuous renal replacement therapy (CRRT). Patients
      receiving CRRT had greater severity of illness than those on hemodialysis. The 1
      year mortality of patients initiating RRT prior to liver transplant was 30%
      versus 9.7% for all other liver recipients (P < 0.0045). CONCLUSION: RRT is
      justifiable for liver transplant candidates with ARF. Though mortality was high,
      a substantial percentage (31%) of patients survived to liver transplant.
      Postoperative mortality is increased compared with all other liver transplant
      recipients, but is acceptable considering the near-universal mortality without
      transplantation.

PMID- 15954929
TI  - Different responses by cultured aortic and venous smooth muscle cells to gamma
      radiation.
AB  - BACKGROUND: Stenosis of hemodialysis arteriovenous grafts is usually focal and
      caused by the proliferation of vascular smooth muscle cells (SMCs). External
      radiation of the graft is a potential strategy to prevent stenosis; however, the
      relative responsiveness of arterial and venous SMCs to radiation is unknown.
      METHODS: Human aortic and saphenous vein SMCs were cultured in a medium
      containing growth factors and serum and treated with 0 to 50 Gy in a gamma
      irradiator. At 2 to 20 days post-irradiation, cell counting,
      methylthiazoletetrazolium dye reduction, [(3)H]-thymidine uptake, and
      bromodeoxyuridine (BrdU) incorporation assays were performed. RESULTS: All assays
      showed that 1 to 50 Gy inhibited the proliferation of both aortic and venous SMCs
      in a dose-dependent manner. Importantly, venous cells were less susceptible to
      radiation in all assays, compared to aortic cells. At day 10, 1 to 50 Gy of
      radiation inhibited the increase in the number of aortic cells by 24% to 66% and
      venous cells by 8% to 25% (P < 0.01) (aortic vs. venous). The differences between
      aortic and venous cells varied among different assays and were most pronounced in
      the BrdU assay. CONCLUSION: Inasmuch as myointimal hyperplasia occurs at both
      arterial and venous anastomoses, future strategies using radiation to prevent
      hemodialysis vascular access stenosis should take these differences into
      consideration.

PMID- 15954930
TI  - Patient education and access of ESRD patients to renal replacement therapies
      beyond in-center hemodialysis.
AB  - BACKGROUND: Nephrologists report that patients' choice should play an important
      role in the selection of renal replacement therapy (RRT) for end-stage renal
      disease (ESRD). In the United States, kidney transplant rates remain low and <10%
      of patients utilize home dialysis therapies. This study examined the effect of
      pre-ESRD processes on the selection of RRT among incident ESRD patients. METHODS:
      Using surveys, data were collected for all patients admitted to 229 dialysis
      units in ESRD Network 18 between April 1, 2002 and May 31, 2002. A total of 1365
      patients began chronic dialysis and 1193 facility (87%) and 428 patient (31%)
      surveys were returned. RESULTS: Substantial proportions of patients were unaware
      of their kidney disease (36%) or were not seeing a nephrologist (36%) until <4
      months before first dialysis. The presentation of treatment options was delayed
      (48% either after or < 1 month before the first dialysis). The majority of ESRD
      patients were not presented with chronic peritoneal dialysis, home hemodialysis,
      or renal transplantation as options (66%, 88%, and 74%, respectively). Using
      multivariate analyses, variables significantly associated with selection of
      chronic peritoneal dialysis as dialysis modality were the probability of chronic
      peritoneal dialysis being presented as a treatment option and the time spent on
      patient education. CONCLUSION: An incomplete presentation of treatment options is
      an important reason for under-utilization of home dialysis therapies and probably
      delays access to transplantation. Improvements in and reimbursement for pre-ESRD
      education could provide an equal and timely access for all medically suitable
      patients to various RRTs.

PMID- 15954931
TI  - Can murine diabetic nephropathy be separated from superimposed acute renal
      failure?
AB  - BACKGROUND: Streptozotocin (STZ) is commonly used to induce diabetes in
      experimental animal models, but not without accompanying cytotoxic effects. This
      study was undertaken to (1) determine an optimal dose and administration route of
      STZ to induce diabetic nephropathy in wild-type mice but without the concurrent
      acute renal injury resulting from cytotoxic effects of STZ and (2) evaluate the
      pattern of tubular injury and interstitial inflammation in this model. METHODS:
      Male Balb/c mice received either (1) STZ (225 mg/kg by intraperitoneal
      injection.); or (2) two doses of STZ 5 days apart (150 mg/150 mg/kg; 75 mg/150
      mg/kg; 75 mg/75 mg/kg; and 100 mg/100 mg/kg by intravenous injection). Another
      strain of mice, C57BL/6J, also received STZ (200 mg/kg intravenously or
      intraperitoneally). Renal function and histology were examined at weeks 1, 2, 4,
      and 8 after induction of diabetes. In initial optimization studies, animals were
      sacrificed at week 1 or week 2 and histology examined for acute renal injury.
      RESULTS: Following a single intraperitoneal injection of 225 mg/kg of STZ, only
      two thirds of animals developed hyperglycemia, yet the model was associated with
      focal areas of acute tubular necrosis (ATN) at week 2. ATN was also observed in
      C57BL/6J mice given a single intravenous or intraperitoneal dose of STZ (200
      mg/kg), at week 2 post-diabetes. At an optimal diabetogenic dose and route (75
      mg/150 mg/kg by intravenous injection 5 days apart), all mice developed diabetes
      and no ATN was observed histologically. However, even with this regimen,
      glomerular filtration rate (GFR) was significantly impaired from week 2. This
      regimen was accompanied by progressive histologic changes, including tubular and
      glomerular hypertrophy, mesangial area expansion, as well as interstitial
      macrophage, CD4+ and CD8+ T-cell accumulation. CONCLUSION: By careful
      optimization of STZ dose, a stable and reproducible diabetic murine model was
      established. However, even in this optimized model, renal functional impairment
      was observed. The frequency of ATN and functional impairment casts doubt on
      conclusions about experimental diabetic nephropathy drawn from reports in which
      ATN has not been excluded rigorously.

PMID- 15954932
TI  - The use of the kidneys in secular and ritual practices according to ancient Greek
      and Byzantine texts.
AB  - The use of kidneys in secular and spiritual practices was very common for
      centuries. In this article we present some references on their employment as
      sacrificial offers, as plain food or as a source for medicaments. Our material
      derives from Greek texts of the Classical, Hellenistic, Roman, and Byzantine
      eras. Relevant extracts from the Old Testament are also included, as they have
      become part of a common cultural heritage in that period of syncretism, when Jews
      were Hellenized and Greeks orientized. From the fragments cited in this article,
      it is obvious that the practical use of kidneys by priests, doctors, and lay
      persons in the periods under discussion was widespread. The sacrificial offering
      was based on the religious significance of the organ. The dietary consumption of
      the kidneys was limited by their function as urine producers. Their medicinal use
      was dictated first, by the abundance of the adipose tissue surrounding them,
      which was an ideal warming and binding substance. Second, it may be explained by
      the deeply rooted conviction that eating a particular organ led to the
      incorporation of its strength, thus protecting the corresponding eater's organs.
      Those practices should not surprise us in view of their corresponding modern use.
      Currently, kidney donors offer their organs in a sacrificial gesture, kidneys are
      consumed as a delicacy worldwide, and renal tissue is therapeutically used in
      transplantations and, until very recently, as a source for hormonal substances.

PMID- 15954933
TI  - Relaxin: exploring the antifibrotic potential of a pregnancy hormone.

PMID- 15954934
TI  - Vasculopathy and renal injury in lupus erythematosus: does shedding of the
      endothelial protein C receptor play a role?

PMID- 15954935
TI  - Hypotonic fluids should not be used in volume-depleted children.

PMID- 15954936
TI  - Antiretroviral drugs and the kidney: further precisions.

PMID- 15954938
TI  - Active vitamin D agents and refractory hyperparathyroidism in dialysis patients.

PMID- 15954939
TI  - Continuous renal replacement therapy in the critically ill patient.

PMID- 15954940
TI  - Combination of intravenous iron sucrose and ascorbic acid in hemodialysis
      patients.

PMID- 15954941
TI  - Dehydration versus volume depletion.

PMID- 15954942
TI  - Herb-associated carcinogenicity and chronic renal failure in Asian patients with
      kidney cancer and hypertension.

PMID- 15954943
TI  - Ethnicity and renal disease.

PMID- 15954945
TI  - Metabolic acidosis: an unrecognized cause of morbidity in the patient with
      chronic kidney disease.
AB  - In patients with chronic kidney disease, metabolic acidosis can occur as a result
      of insufficient ammoniagenesis within the damaged kidney. This, in turn, can
      bring about a variety of sequella that have their basis in hormonal and cellular
      abnormalities that effect stunted growth, loss of muscle and bone mass, and
      negative nitrogen balance. Cellular mechanisms accounting for these findings are
      reviewed. In bone, metabolic acidosis causes direct dissolution of bone;
      ostoeclastic activity is increased while osteoblastic activity is suppressed. In
      muscle, branched-chain amino acid oxidation is increased and the ubiquitin
      proteasome pathway is activated: muscle wasting results. Even a modest degree of
      metabolic acidosis can be harmful and can initiate a series of maladaptive
      responses that are not easily reversed, although there is evidence that alkali
      therapy can be beneficial in reversing these responses.

PMID- 15954946
TI  - An introduction to phosphate binders for the treatment of hyperphosphatemia in
      patients with chronic kidney disease.
AB  - Chronic kidney disease has the potential to induce sequelae that can have severe
      and mortal outcomes. In particular, impaired glomerular filtration can cause a
      hyperphosphatemic state, which, if left unchecked, can lead to secondary
      hyperparathyroidism, vascular calcification, and renal osteodystrophy.
      Therapeutic management of hyperphosphatemia must maintain both phosphorus and
      calcium serum concentrations within the recommended guidelines. The balance of
      both minerals is regulated by parathyroid hormone; thus, an imbalance of one
      affects the other. In end-stage renal disease, patients often present with
      hypocalcemic levels due to the kidneys' inability to generate active vitamin D to
      promote calcium absorption in the intestine. Absorption of calcium can be
      increased by the administration of active vitamin D analogues. Minimizing
      phosphorus intake through a strict dietary regimen, combined with the use of
      phosphate binders to absorb excess ingested phosphate, can help to maintain serum
      phosphate levels near the recommended concentration of 5.5 mg/dL. Phosphate
      binding compounds have evolved from the original aluminum-based binders pioneered
      in the 1970s to calcium-based binders such as calcium acetate, and more recently,
      to the following additions to the nephrologist's armamentarium: sevelamer--a
      polyhydrochloride polymer, and lanthanum carbonate. One of the top 2 common
      clinical treatments for hyperphosphatemia, calcium acetate, has an established
      history of efficacy since the 1980s, and has been shown to be cost effective and
      well tolerated, as well.

PMID- 15954947
TI  - Cinacalcet HCl: a novel treatment for secondary hyperparathyroidism in stage 5
      chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) alters the regulation of calcium and
      phosphate homeostasis, leading to secondary hyperparathyroidism, metabolic bone
      disease, soft tissue calcifications, and other metabolic derangements that have a
      significant impact on morbidity and mortality. The parathyroid gland is the
      central organ responsible for regulating these adaptive responses. Suppression of
      parathyroid hormone (PTH) secretion, hypertrophy, and hyperplasia are a major
      goal of treatment of CKD. METHODS: Current literature was reviewed and combined
      with the author's experience to address a number of issues regarding the optimal
      treatment of secondary hyperparathyroidism in hemodialysis patients. RESULTS: The
      calcium sensing receptor (CASR) is the most important factor regulating
      parathyroid gland function, and allosteric modulators of CASR, called
      calcimimetics, provide a novel drug therapy to suppress PTH secretion. The
      current use of active vitamin D analogues to suppress PTH is often limited by
      hypercalcemia and hyperphosphatemia. Clinical trials of cinacalcet HCl, the first
      calcimimetic to be approved for treatment of secondary hyperparathyroidism in
      CKD, have demonstrated suppression of circulating PTH levels without increments
      in the calcium-phosphorus (Ca x P) product, making it easier to achieve the
      stringent management guidelines proposed for subjects with CKD by the National
      Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI).
      CONCLUSION: The management of disordered calcium and phosphate homeostasis in CKD
      patients is evolving based on our knowledge of the major importance of the
      calcium sensing receptor (CASR) in controlling parathyroid gland function and the
      potent actions of calcimimetics to target CASR. The purpose of this presentation
      is to provide an overview of the role of the CASR in regulation of parathyroid
      gland function, to examine the mechanisms whereby calcimimetics target the CASR,
      and to review the clinical trials that support the use of cinacalcet HCl for the
      treatment of secondary hyperparathyroidism in stage 5 chronic kidney disease
      (CKD).

PMID- 15954948
TI  - Phosphate binder therapy for attainment of K/DOQI bone metabolism guidelines.
AB  - Hyperphosphatemia in patients with chronic kidney disease leads to secondary
      hyperparathyroidism and renal osteodystrophy, and it is independently associated
      with mortality risk. The exact mechanism by which hyperphosphatemia increases
      mortality risk is unknown, but it may relate to enhanced cardiovascular
      calcification. The National Kidney Foundation Kidney Disease Outcomes Quality
      Initiative (K/DOQI) Clinical Practice Guidelines for Bone Metabolism and Disease
      in Chronic Kidney Disease recommends maintenance of serum phosphorus below 5.5
      mg/dL, calcium-phosphorus (Ca x P) product less than 55 mg(2)/dL(2), intact
      parathyroid hormone (iPTH) 150 pg/mL to 300 pg/mL, and bicarbonate (HCO(3))
      greater than 22 mEq/L. Although calcium-based phosphate binders (CBPB) are cost
      effective, there are long-term safety concerns pertaining to their postulated
      role in the progression of cardiovascular calcification. Sevelamer hydrochloride
      has been recommended as an alternative noncalcium phosphate binder. Results from
      the Calcium Acetate Renagel Evaluation (CARE) study indicate that calcium acetate
      is more effective than sevelamer hydrochloride in controlling serum phosphorous,
      Ca x P product, and HCO(3) in hemodialysis patients. In the Treat-to-Goal study,
      dialysis patients treated with sevelamer hydrochloride had slower progression of
      coronary and aortic calcification than patients treated with CBPB. The mechanism
      underlying the beneficial effect of sevelamer hydrochloride is unknown but may
      relate to decreased calcium loading, or to dramatic reductions in low-density
      lipoprotein (LDL) cholesterol in sevelamer hydrochloride-treated patients. At
      present, evidence incriminating CBPB in the progression of cardiovascular
      calcification in end-stage renal disease (ESRD) remains largely circumstantial.
      As calcium acetate is more efficacious and cost effective than sevelamer
      hydrochloride, it remains an accepted first-line phosphate binder. This review
      examines these issues and provides rational guidelines for the use of CBPB in
      patients on maintenance hemodialysis.

PMID- 15954949
TI  - Disclosure.

PMID- 15954950
TI  - Aftermath of an adverse event: supporting health care professionals to meet
      patient expectations through open disclosure.
AB  - An important element of how adverse events are handled is effective communication
      between health care providers and patients and their families. This review
      addresses the main questions: What do patients expect in the aftermath of an
      adverse event? What is known about the practice of open disclosure? How can
      organizations support health care providers in the aftermath of an adverse event,
      both professionally and personally? Patients clearly expect open disclosure to
      include an explanation of what happened, an apology for harm done, that
      appropriate remedial action will be taken and an explanation of what will be done
      to learn from the event and to prevent recurrence. Research has found that open
      disclosure is not very common although the ethical duty to disclose is widely
      acknowledged. Barriers to open disclosure include discomfort and a lack of
      training how to disclose, a fear of litigation, a culture of infallibility among
      health professionals, and inadequate systems for analysis, discussion and
      learning from mistakes. Significant commitment is required from health care
      organizations and managers to develop frameworks for open disclosure to occur, to
      assure its quality and to support health care providers in this process.
      Organizations also need to address the emotional needs of health care
      professionals in the aftermath of an adverse event. Last but not least, adequate
      systems for debriefing and incident analysis need to be in place to learn from
      adverse events and to avoid recurrence.

PMID- 15954951
TI  - Emotional and interpersonal factors are most important for patient satisfaction
      with anaesthesia.
AB  - BACKGROUND: Questionnaires to evaluate patient satisfaction with anaesthesia
      mainly consider physiological aspects. This study was performed to identify the
      items of value for patients having anaesthesia (pilot phase) and to validate the
      questionnaire built on these findings in a new group of inpatients. METHODS: In
      the pilot phase, 100 surgical patients were interviewed and asked whether each of
      the 23 items selected by a panel of providers was relevant (score 1) and to rank
      these from 1 (additional score 6) to 5 (additional score 2). The resulting 10
      item final instrument was administered to 219 consecutive inpatients by
      interview, after recent anaesthesia, asking them how much of each item they
      received (item received) and the level of satisfaction with the same item, using
      Numerical Rating Scales (range 0-10). RESULTS: In the pilot phase, gender, age,
      education and surgery did not influence the score enough to change the first 10
      rank-ordered items. The 219 patients subsequently studied did not differ from
      those missing the questionnaire administration. The patients aged less than 55
      years showed lower satisfaction scores than those aged 55 years or more (P =
      0.019). In all items, except 'feeling anxious/frightened', the item received was
      significantly associated with the satisfaction reported. 'Kindness/regard of
      caregivers' together with 'information given by anaesthetist' and 'feeling safe'
      predicted 47% of the variance in total patient satisfaction. CONCLUSIONS:
      Inpatients value highly those elements of care that pertain to emotional and
      interpersonal relationships.

PMID- 15954952
TI  - Xenon anaesthesia may preserve cardiovascular function in patients with heart
      failure.
AB  - BACKGROUND: The hypothesis that xenon anaesthesia provided haemodynamic stability
      was tested in patients with heart failure in a prospective, randomized, single
      blind design. METHODS: Twenty-six patients scheduled for implantation of a
      cardioverter-defibrillator (ICD) received xenon 60-65% in oxygen (xenon group, n
      = 12) or propofol 3 mg/kg/h (propofol group, n = 14), both combined with
      remifentanil 0.2 microg/kg/min. After induction of anaesthesia with etomidate and
      remifentanil, heart rate (HR), mean arterial pressure (MAP) and left ventricular
      ejection fraction (LVEF) were recorded. After 60 min of propofol or xenon
      anaesthesia, the same parameters were recorded. RESULTS: While HR decreased in
      both groups, MAP was unchanged with xenon (73 vs. 76 mmHg) and decreased with
      propofol (from 78 to 64 mmHg, P < 0.02). LVEF was stable in both groups [32% vs.
      37%, xenon (NS), and 30% vs. 34%, propofol (NS)]. Preload, as measured by end
      diastolic volume (EDV), did not change (66 vs. 63 ml with xenon; 79 vs. 81 ml
      with propofol, both NS). Afterload, as determined by end-systolic pressure-volume
      product (ESPV), decreased with propofol (6760 vs. 4920 ml mmHg) but not with
      xenon (4060 vs. 3780 ml mmHg, P < 0.01 between groups). CONCLUSION: With
      propofol, MAP is reduced and LVEF is not increased in spite of reduced afterload.
      In contrast, MAP and LVEF are maintained with xenon.

PMID- 15954953
TI  - Cerebral state index during anaesthetic induction: a comparative study with
      propofol or nitrous oxide.
AB  - BACKGROUND: Confidently predicting the depth of anaesthesia for the individual
      patient and independently of drug(s) type using EEG-based monitors has proven
      difficult. This open, randomized, explorative study of day surgical patients
      evaluates the ability of the Cerebral State Monitor (Danmeter AB, Odense,
      Denmark) of anaesthetic depth to identify loss of response (LOR) using either
      propofol or N(2)0 for induction. METHODS: In this open, randomized study, day
      surgical patients (n=10 in each group) were studied using the Cerebral State
      Index Monitor. After baseline measurements, induction to LOR was achieved with
      either repeated 30-mg boluses of propofol every second minute or with N(2)0
      (after premedication 5 min before with 30 mg propofol) increased every other
      minute in 15% increments (max. 75%). Sedation level was evaluated every other
      minute using the Observer's Assessment of Alertness/Sedation scale. RESULTS:
      Baseline values were 91 (82-98) and 94 (82-100) for N(2)0 and propofol patients,
      respectively. During induction CSI decreased with increasing sedation in patients
      given propofol (P<0.001) but not in patients given nitrous oxide. Median value at
      LOR was 56 (40-76) and 95 (87-100) for the propofol and nitrous oxide group of
      patients, respectively. CONCLUSION: The Cerebral State Index(trade mark) behaves
      as other depth of anaesthesia monitors with a progressive decrease during
      propofol induction but loss of consciousness with N(2)0 results in no change in
      CSI.

PMID- 15954954
TI  - Desflurane induces more cerebral vasodilation than isoflurane at the same A-line
      autoregressive index level.
AB  - BACKGROUND: Clinical use of desflurane in neuroanesthesia remains under debate.
      Comparison of dose-dependent vasodilatory properties between desflurane and
      isoflurane, the more traditional volatile agent for clinical neuroanesthesia,
      requires equianesthetic dosing of the agents. Reproducible neurophysiological
      measurements of the level of anesthesia in an individual, e.g. the A-line
      autoregressive index (AAI), can be used for an equipotent dosage of two volatile
      agents in the same individual. METHODS: Desflurane and isoflurane, in randomized
      order, were titrated to a stable AAI level of 15-20 in 18 ASA I or II patients.
      The mean flow velocity (Vmca) and pulsatility index (PI) in the middle cerebral
      artery were then measured with transcranial Doppler at an end-tidal CO(2)
      concentration of 4.4%. RESULTS: For desflurane Vmca was 11% higher [95%
      confidence interval (CI), 5-18%; P = 0.0020] and PI was 13% lower (95% CI, 3-23%;
      P = 0.0083) than for isoflurane. The mean arterial blood pressure did not differ
      between the agents. The fraction of MAC necessary for the intended AAI level was
      35% lower (95% CI, 20-49%; P = 0.00016) with desflurane than with isoflurane.
      CONCLUSION: Desflurane was associated with more cerebral vasodilation than
      isoflurane at the same depth of anesthesia, as indicated by the AAI. This
      attributes further reason for caution in the use of desflurane in clinical
      neuroanesthesia. The difference between desflurane and isoflurane in the MAC
      fractions required for the same AAI level confirms the limitations of MAC in
      defining the level of anesthesia.

PMID- 15954955
TI  - Relationship between arterial and end-tidal carbon dioxide pressures during
      anesthesia using a laryngeal tube.
AB  - BACKGROUND: The Laryngeal Tube (LT), (VBM Medizintechnik, Sulz, Germany) is a
      relatively new supraglottic device for controlling the airway. Arterial carbon
      dioxide tension (PaCO(2)) can be estimated by monitoring the end-tidal tension of
      carbon dioxide (PETCO(2)). The relationship between PETCO(2) and PaCO(2) during
      controlled ventilation via the LT has not been reported. METHODS: During general
      anesthesia, 45 patients were mechanically ventilated using an LT. PETCO(2) and
      PaCO(2) were measured once PETCO(2) had reached a steady state. The LT was then
      removed and the trachea intubated using an endotracheal tube (ETT), and the
      identical ventilatory variables were resumed. Following stabilization, PETCO(2)
      was again determined and PaCO(2) estimated. RESULTS: The mean PETCO(2) and
      PaCO(2) values were 4.43 +/- 0.26 kPa and 4.67 +/- 0.32 kPa, respectively, during
      LT ventilation, and 4.36 +/- 0.23 kPa and 4.61 +/- 0.26 kPa, respectively, during
      ETT ventilation. Analysis of differences between the PETCO(2) and PaCO(2) values
      using the Bland and Altman method revealed a bias +/- precision of 0.24 +/- 0.15
      kPa for LT and 0.27 +/- 0.15 kPa for ETT. The root mean square error was 0.28 for
      the LT and 0.30 for the ETT. CONCLUSION: This study suggests that for healthy
      adult patients mechanically ventilated via the LT, the PETCO(2) value reflects
      the PaCO(2) value as closely as when patients are ETT ventilated, allowing
      capnometry to be used to evaluate the adequacy of ventilation.

PMID- 15954956
TI  - Intrathecal picrotoxin minimally alters electro-encephalographic responses to
      noxious stimulation during halothane and isoflurane anesthesia.
AB  - BACKGROUND: Isoflurane and halothane act in the spinal cord to blunt ascending
      transmission of impulses to the brain resulting from noxious stimulation. Because
      intrathecal picrotoxin (an antagonist at the gamma-aminobutyric acid-A receptor)
      partially reverses the immobilizing effect of isoflurane and halothane, we
      hypothesized that the electroencephalographic response to noxious stimulation
      would likewise be partially reversed by intrathecal picrotoxin. METHODS: Rats
      were anesthetized with isoflurane (n = 8) or halothane (n = 8) and a laminectomy
      performed. Following determination of minimum alveolar concentration (MAC), the
      electroencephalogram (EEG) was recorded during separate applications of a hindpaw
      clamp, tail clamp and electrical current to the tail at 0.8 and 1.2 MAC.
      Picrotoxin was then applied to the exposed spinal cord and the EEG response to
      noxious stimulation again determined. RESULTS: The EEG was more active during
      halothane anesthesia than isoflurane (spectral edge frequency for 95% power: 25.6
      +/- 2.1 Hz vs. 23.1 +/- 1.6 Hz, P < 0.05). Noxious stimulation usually caused the
      EEG to shift to higher frequencies (e.g. for 0.8 MAC halothane, median edge
      frequency for 50% power: from 7.6 +/- 3.1 Hz to 10.7 +/- 2.6 Hz, P < 0.05).
      Picrotoxin minimally affected this response. CONCLUSIONS: Noxious stimulation
      evokes an EEG response that is minimally altered by intrathecal picrotoxin. This
      suggests that isoflurane and halothane do not have GABAergic actions in the
      spinal cord that indirectly suppress the EEG response.

PMID- 15954957
TI  - Nociceptin system does not affect MAC of volatile anaesthetics.
AB  - BACKGROUND: Nociceptin is the endogenous agonist of the opioid receptor-like
      (ORL) 1 receptor (NOP), and both nociceptin and NOP are widely expressed in the
      brain and spinal cord, which are target organs of general anaesthetics. As
      nociceptin has been reported to be involved in modulating pain mechanisms and
      stress responses, it is possible that the activity of the nociceptin system
      affects the anaesthetic potency of general anaesthetics. To address this
      possibility, we investigated the minimum alveolar concentrations (MACs) of
      various volatile anaesthetics in nociceptin receptor knockout mice (NOP-/-) and
      wild-type mice (NOP+/+). METHODS: We used male NOP-/- mice and NOP+/+ mice. MACs
      for halothane, isoflurane and sevoflurane were determined by the tail-clamp
      method. RESULTS: MACs for halothane, isoflurane and sevoflurane in NOP-/- mice
      were 1.60 (SD 0.06), 1.68 (0.08) and 3.36 (0.07)%, respectively. In NOP+/+ mice,
      MACs for halothane, isoflurane and sevoflurane were 1.59 (SD 0.07), 1.72 (0.07)
      and 3.38 (0.09)%, respectively. CONCLUSION: MACs in NOP-/- mice did not
      significantly differ from those in NOP+/+ mice for halothane, isoflurane and
      sevoflurane. This result suggests that the nociceptin system does not affect the
      anaesthetic potency of volatile anaesthetics.

PMID- 15954958
TI  - Auditory-evoked potentials in general anesthesia monitoring: baseline study of
      availability in relation to hearing function in awake status.
AB  - BACKGROUND: It has been confirmed that middle latency auditory-evoked potentials
      are good indicators of the hypnotic level in patients undergoing general
      anesthesia. The focal point for the evocation of auditory-evoked potentials is
      the presence of a serviceable hearing function. The aim of the study was to
      evaluate the limit of hearing loss above which the test could not be applied.
      METHODS: To determine the limit of applicability of the technique, 100 subjects
      were studied. Twenty of them were normally hearing and 80 were affected by
      sensorineural hearing loss of various degrees. Each subject was submitted to pure
      tone audiometry, to determine hearing threshold, and then, in awake status, to
      auditory-evoked potentials recording using acoustic stimuli of 85 dB HL. RESULTS:
      All the 20 normally hearing subjects showed a reliable auditory-evoked
      potentials. Among the 80 subjects affected by hearing loss, only five had no
      potentials. These five subjects presented a pure tone audiometry threshold
      greater than 85 dB HL. CONCLUSION: The study demonstrated that middle latency
      auditory-evoked potentials recorded using an A-Line (software version 1.4) AEP
      monitor (Danmeter, Odense, Denmark) can be carried out even in presence of
      hearing loss if the pure tone threshold is less than 85 dB HL.

PMID- 15954959
TI  - Positive end-expiratory pressure improves arterial oxygenation during prolonged
      pneumoperitoneum.
AB  - BACKGROUND: Laparoscopic surgery usually requires the use of a pneumoperitoneum
      by insufflating gas in the peritoneal space. The gas most commonly used for
      insufflation is carbon dioxide. Increased intra-abdominal pressure causes
      cephalad displacement of the diaphragm resulting in compressed lung areas, which
      leads to formation of atelectasis, especially during mechanical ventilation. The
      aim of this prospective study was to investigate the effect of prolonged
      intraperitoneal gas insufflation on arterial oxygenation and hemodynamics during
      mechanical ventilation with and without positive end-expiratory pressure (PEEP).
      METHODS: Twenty patients undergoing totally endoscopic robot-assisted radical
      prostatectomy were randomly allocated to one of two groups. In the PEEP group (n
      = 10) a constant PEEP of 5 cmH(2)O was used, whereas in the ZPEEP group (n = 10)
      no PEEP was used. RESULTS: Application of PEEP (5 cmH(2)O) resulted in
      significantly higher P(a)O(2) levels after 3 h (182 +/- 49 vs. 224 +/- 35 mmHg)
      and 4 h (179 +/- 48 vs. 229 +/- 29 mmHg) of pneumoperitoneum; after desufflation,
      P(a)O(2) values decreased significantly below preinsufflation values. While there
      were no significant differences in heart rate, central venous pressure (CVP) and
      mean arterial blood pressure (MAP) during pneumoperitoneum between both groups,
      baseline values in CVP and MAP differed significantly between both groups with
      higher levels in the ZPEEP group. CONCLUSION: The application of a constant
      positive airway pressure of 5 cmH(2)O preserves arterial oxygenation during
      prolonged pneumoperitoneum.

PMID- 15954960
TI  - Propofol attenuates responses of the auditory cortex to acoustic stimulation in a
      dose-dependent manner: a FMRI study.
AB  - BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level
      dependent (BOLD) contrasts is a common method for studying sensory or cognitive
      brain functions. The aim of the present study was to assess the effect of the
      intravenous anaesthetic propofol on auditory-induced brain activation using BOLD
      contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were
      presented binaurally in a block design. Imaging was performed under five
      conditions: no propofol (or wakefulness) and propofol plasma target
      concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During
      wakefulness we found activations in the superior temporal gyrus (STG)
      corresponding to the primary and secondary auditory cortex as well as in regions
      of higher functions of auditory information processing. The BOLD response
      decreased with increasing concentrations of propofol but remained partially
      preserved in areas of basic auditory processing in the STG during propofol 2.0
      microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of
      central processing of auditory information after propofol administration. These
      results are consistent with electrophysiological findings measuring neuronal
      activity directly, thus suggesting a dose-dependent impairment of central
      processing of auditory information after propofol administration. However,
      propofol did not totally blunt primary cortical responses to acoustic
      stimulation, indicating that patients may process auditory information under
      general anaesthesia.

PMID- 15954961
TI  - Effects of ephedrine on intubating conditions following priming with rocuronium.
AB  - BACKGROUND: Onset of action of muscle relaxants is influenced by cardiac output
      and muscle blood flow. Ephedrine reduces the onset time of rocuronium. Onset is
      also shortened by priming. Accordingly, we hypothesized that priming combined
      with ephedrine is superior to either technique used separately. METHODS: Four
      groups of randomly allocated patients (n = 31), ASA I - II, were induced with
      propofol 2.5 mg kg(-1). In groups I and II, 0.04 mg kg(-1) of rocuronium was
      followed by a 3-min priming interval. Induction was followed by an intubation
      dose of 0.04 mg kg(-1). Then a 30-s intubation was attempted. In groups III and
      IV the same sequence was repeated except for sham priming and an intubation dose
      of 0.44 mg kg(-1). In groups I and II, ephedrine (210 microg kg(-1)) was injected
      before propofol. In groups II and V, an equivalent volume of normal saline was
      injected. Jaw relaxation, vocal cord position, and diaphragmatic response were
      used to assess intubating conditions. RESULTS: All patients of group I were
      intubated 30 s after the intubating dose and within a 20-s interval compared with
      74% of patients in groups II and III, and 84% of patients in group IV. Intubating
      conditions were graded good to excellent in all patients in group I compared with
      42% of those in group II, 35% in group III and 52% in group IV (P < 0.01 vs.
      group I). During the priming interval, no adverse effects were observed or
      reported. CONCLUSIONS: Ephedrine in combination with propofol significantly
      improved clinical intubating conditions at 30 s following priming with rocuronium
      compared with priming with ephedrine without priming.

PMID- 15954962
TI  - Palmar skin conductance compared to a developed stress score and to noxious and
      awakening stimuli on patients in anaesthesia.
AB  - BACKGROUND: The number of fluctuations in the skin conductance per s (NFSC) as a
      measure of the sympathetic nervous system may be a tool for monitoring
      physiological stress during surgery and general anaesthesia. The purpose of this
      study was to find the sensitivity and specificity of the NFSC when compared to a
      peroperative clinical stress score. Moreover, different patterns of skin
      conductance responses were compared with the BIS score to find out if the mean
      level of skin conductance (SC) and NFSC monitoring could differentiate between
      awakening and noxious stimuli. METHODS: Fourteen patients were studied during
      stressful or non-stressful registration periods. During each registration period,
      the NFSC was compared to a five-point clinical stress score (CSS) (systolic blood
      pressure >130 mmHg, cough, tears, EMG in the forehead >50 or movements) and BIS
      score. RESULTS: The NFSC and the CSS both indicated physiological stress at 12
      registrations and no stress at 186 registrations. The NFSC indicated
      physiological stress without signs of clinical stress (CSS = 0) in 28
      registrations, whereas signs of clinical stress (CSS > 0) were indicated on two
      occasions without signs of stress in the NFSC. The sensitivity of the NFSC when
      compared to the CSS was 86% and the specificity was 86%. Moreover, in all
      situations (n = 16) where NFSC indicated stress and the BIS score >50, the SC
      increased. This was different from situations (n = 13) where NFSC indicated
      stress and the BIS score <50, then the SC did not increase (P < 0.001).
      CONCLUSION: The NFSC is sensitive to clinical stress during surgical stimulation.
      Moreover, the combined use of SC and NFSC may have a potential to differentiate
      between situations of stress due to inadequate hypnotic effect vs. inadequate
      analgesic effect.

PMID- 15954963
TI  - Plasma propofol concentrations during orthotopic liver transplantation.
AB  - OBJECTIVE: The aim of this study was to investigate the changes in plasma
      concentrations of propofol in three phases (the paleohepatic, anhepatic, and
      neohepatic phases) during orthotopic liver transplantation (OLT) using target
      controlled infusion (TCI). METHODS: Ten patients undergoing OLT without
      venovenous bypass were studied (age 29-53 years, weight 56-79 kg). After
      intubation, a non-hypnotic target concentration of propofol 0.5 microg ml(-1)
      using a Diprifusor pump (Zeneca Pharmaceuticals, Macclesfield, UK) was
      administered as a supplement anesthesia throughout the procedure. Plasma samples
      were obtained in each phase for propofol assay, respectively. Performance
      parameters for the Diprifusor system in each phase, the percentage median
      performance error (MDPE), the percentage median absolute performance error
      (MDAPE), and the percentage median absolute constancy error (MDACE) were
      evaluated. RESULTS: In all patients, measured plasma propofol concentrations were
      several times higher than Diprifusor values in each phase during the procedure.
      In nine patients, propofol concentrations in the anhepatic phase were higher than
      those in the paleohepatic or neohepatic phase (P < 0.05). There were no
      significant differences between the paleohepatic and neohepatic phases.
      Interindividual variation of the plasma propofol concentrations was significant
      (P < 0.05). Percentage median performance error of Diprifusor in each phase, as
      well as MDAPE, was large (>300%) and was significantly higher in the anhepatic
      phase (P < 0.01), whereas MDACE was relatively small and there was no significant
      difference between phases. CONCLUSIONS: Models used by Diprifusor are not
      suitable for liver transplantation patients. A further study should be performed
      in order to determine all pharmacokinetic parameters of propofol in these
      patients.

PMID- 15954964
TI  - Does repetition of post-tetanic count every 3 min during profound relaxation
      affect accelerographic recovery of atracurium blockade?
AB  - BACKGROUND: Post-tetanic count is a valuable method to assess profound
      neuromuscular blockade. However, subsequent responses to repetitive stimulation
      might be altered due to post tetanic facilitation (PTF). To avoid PTF, it has
      been advocated to limit the interval of stimulation from 6 to 10 min. The impact
      of PTF on 90% recovery of the TOF ratio has not been evaluated. Therefore, we
      assessed the effect of repetitive PTC stimulation on atracurium blockade with the
      primary outcome being the time to reach 90% TOF recovery in comparison to
      classical TOF stimulation. METHODS: After informed consent 20 patients ASA I-II,
      scheduled for peripheral surgery under general anaesthesia and requiring tracheal
      intubation were enrolled into the study. Anaesthesia was induced with fentanyl,
      propofol, and atracurium, 0.5 mg kg(-1). Neuromuscular characteristics were
      assessed at the adductor pollicis by a TOF Watch((R)) accelerometer (Organon,
      Teknika, Holland) on each arm. After onset of maximum neuromuscular blockade,
      repetitive PTC every 3 min on one arm and repetitive TOF stimulation every 15 s
      on the opposite arm was performed. The following parameters were recorded: onset
      of maximum blockade, mean time of PTC stimulation, the maximum number of
      responses to PTC, time of the first and second TOF responses, and recovery
      profile until 90% TOF ratio. RESULTS: Time to reach 90% TOF recovery was similar
      on both arms (48 +/- 9 min), with a difference of 16 +/- 38 s between the arms (P
      = 0.64). The first and second responses of the TOF on the PTC-stimulated arm
      appeared at 29 +/- 8 min and 33 +/- 7 min, respectively. On the other arm the
      responses appeared at 30 +/- 8 min and 35 +/- 8 min, respectively (P < 0.05).
      CONCLUSION: Repetitive PTC stimulation every 3 min hastened the first and second
      responses of the TOF stimulation but we could not detect a significant difference
      in the 90% recovery of TOF ratio during atracurium blockade.

PMID- 15954965
TI  - Carbon monoxide production from desflurane and six types of carbon dioxide
      absorbents in a patient model.
AB  - BACKGROUND: Desflurane is known to produce high concentrations of carbon monoxide
      (CO) in desiccated sodalime or Baralyme (Allied Healthcare Products, St. Louis,
      MO). Desiccated absorbents without strong bases like potassium hydroxide or
      sodium hydroxide are reported to produce less or no CO at all. The purpose of
      this study is to compare the concentration of CO in an anesthesia circuit for
      desflurane with six different types of completely desiccated CO(2) absorbents
      with less strong bases than sodalime. METHODS: A patient model was simulated
      using a circle anesthesia system connected to an artificial lung. Completely
      desiccated CO(2) absorbent (950 g) was used in this system. A low flow anesthesia
      (500 ml min(-1)) was maintained using desflurane. For immediate quantification of
      CO production a portable gas chromatograph was used. RESULTS: Peak concentrations
      of CO were very high in Medisorb (Datex-Ohmeda, Hoevelaken, The Netherlands) and
      Spherasorb (Intersurgical, Uden, The Netherlands) (13317 and 9045 p.p.m.,
      respectively). It was lower with Loflosorb (Intersurgical, Uden, The Netherlands)
      and Superia (Datex-Ohmeda, Hoevelaken, The Netherlands) (524 and 31 p.p.m.,
      respectively). Amsorb (Armstrong, Coleraine, N. Ireland) and lithium hydroxide
      produced no CO at all. CONCLUSION: Medisorb and Spherasorb are capable of
      producing large concentrations of CO when desiccated. Loflosorb and Superia
      produce far less CO under the same conditions. Amsorb and lithium hydroxide
      should be considered safe when desiccated.

PMID- 15954966
TI  - Effects of phosphodiesterase-III inhibitors on sevoflurane-induced impairment of
      rat diaphragmatic function.
AB  - BACKGROUND: Volatile anesthetics are known to cause diaphragmatic dysfunction
      using a whole body model. The first aim of the current study was to compare the
      impairing effect of halothane and sevoflurane on diaphragmatic contractile
      functions under unfatigued and fatigued conditions. The second purpose was to
      determine whether phosphodiesterase-III inhibitors can attenuate sevoflurane
      potentiated reduction of contractility after fatigue. METHODS: Using rat-isolated
      muscle strips, diaphragmatic twitch characteristics and tetanic contractions were
      measured before and after muscle fatigue, which was induced by repetitive tetanic
      contraction with or without exposure to halothane (1-3 MAC) or sevoflurane (1-3
      MAC). Diaphragmatic functions were further assessed with exposure to 3 MAC
      sevoflurane in the presence and absence of milrinone, or olprinone. Cyclic
      adenosine monophosphate (cAMP) concentrations in the fatigued diaphragm were also
      measured. RESULTS: Halothane (1-3 MAC) or sevoflurane (1-2 MAC) did not induce a
      direct inotropic effect under unfatigued and fatigued conditions. Sevoflurane at
      3 MAC enhanced fatigue-induced impairment of twitch and tetanic tensions.
      Clinically relevant concentrations of olprinone improved the sevoflurane-induced
      potentiation of diaphragmatic dysfunction following fatigue, accompanied by
      restoration of diaphragmatic cAMP levels, although milrinone failed to do so.
      CONCLUSION: Our findings suggest that sevoflurane has a greater decreasing effect
      on diaphragmatic contractility after fatigue than halothane, and that the
      clinical dose of olprinone surmounts the disadvantage of sevoflurane in various
      conditions where diaphragmatic fatigue is predisposed.

PMID- 15954967
TI  - Mixed venous oxygen desaturation during early mobilization after coronary artery
      bypass surgery.
AB  - BACKGROUND: Early postoperative mobilization induces a marked reduction in mixed
      venous oxygen saturation (S(v)O(2)) after aortic valve replacement. We
      investigated whether a similar desaturation occurs among coronary artery bypass
      grafting (CABG) patients, and if the desaturation was related to the preoperative
      ejection fraction (EF). METHODS: Thirty-one CABG patients with a wide range in EF
      were included in an open observational study. We recorded hemodynamic and
      oxygenation variables during mobilization on postoperative day 1 and day 2 using
      a pulmonary artery catheter. RESULTS: Patients with an EF ranging from 24 to 87%
      were mobilized without clinical problems. S(v)O(2) at rest was 65.4 +/- 4.9%
      (mean +/- SD) on day 1 and 64.3 +/- 5.8% on day 2 (NS). During mobilization,
      cardiac index and oxygen delivery were reduced while oxygen consumption was
      increased (P-values: 0.000, 0.007 and 0.000, respectively). Consequently, oxygen
      extraction increased, resulting in a marked reduction in S(v)O(2)-42.9 +/- 8.3%
      on day 1 and 47.4 +/- 8.5% on day 2 (P = 0.025 between days). Several pre-, intra
      and postoperative factors were tested as possible predictors for S(v)O(2) during
      mobilization. No factor contributed substantially. CONCLUSION: Patients with CABG
      exhibit a marked desaturation during early postoperative mobilization.
      Preoperative ejection fraction did not affect S(v)O(2) during exercise. The
      clinical consequences and underlying mechanism require further investigation.

PMID- 15954968
TI  - Effects of sevoflurane and desflurane on cytokine response during tympanoplasty
      surgery.
AB  - BACKGROUND: This study was devised to compare the effects of sevoflurane and
      desflurane anaesthesia on the cytokine response. METHODS: Sixty ASA I-II
      patients, scheduled for tympanoplasty, were randomly allocated to be
      anaesthetized with either sevoflurane or desflurane at maintenance inspiratory
      concentrations of 1-1.5 MAC of either agent. Blood samples were taken for plasma
      tumour necrosis factor alpha (TNFalpha), interleukin 1beta and interleukin-6
      assay before induction of anaesthesia, before surgery, and at the end of surgery.
      Alveolar cells were obtained after induction of anaesthesia and at the end of
      surgery. RESULTS: Plasma TNFalpha was greater with desflurane than sevoflurane
      both before surgery (45.1 +/- 3.5 pg ml(-1) for desflurane vs. 23.2 +/- 2.5 pg
      ml(-1) for sevoflurane, P < 0.01) and (62.0 +/- 5.3 pg ml(-1) vs. 35.5 +/- 4.6 pg
      ml(-1), P < 0.001). Interleukin 1beta was similarly greater with desflurane than
      sevoflurane before (39.3 +/- 4.0 pg ml(-1) vs. 17.4 +/- 3.0 pg ml(-1); P < 0.01)
      and after surgery (46.0 +/- 3.4 pg ml(-1) vs. 23.3 +/- 3.2 pg ml(-1), P < 0.001).
      There were similar results for interleukin 6 before (42.3 +/- 3.5 pg mls(-1).
      29.0 +/- 2.6 pg ml(-1), P < 0.001) and after surgery (86.0 +/- 4.5 pg ml(-1) vs.
      45.9 +/- 6.3 pg ml(-1), P < 0.001). Alveolar cell TNFalpha concentrations after
      surgery were also greater with desflurane than sevoflurane (96.3 +/- 12.4 pg ml(
      1) vs. 64.8 +/- 10.1 pg ml(-1), P < 0.001), as were interleukin 1beta (75.4 +/-
      6.2 pg ml(-1) vs. 32.0 +/- 8.3 pg ml(-1), P < 0.001) and interleukin 6
      concentrations (540.1 +/- 65.3 pg ml(-1) vs. 363.6 +/- 29.2 pg ml(-1), P <
      0.001). CONCLUSION: Desflurane appears to cause a greater systemic and
      intrapulmonary pro-inflammatory response than sevoflurane during anaesthesia for
      ear surgery.

PMID- 15954969
TI  - Characterization of inhibition of platelet function by paracetamol and its
      interaction with diclofenac in vitro.
AB  - BACKGROUND: Paracetamol (acetaminophen) is an effective analgesic and a weak
      inhibitor of cyclo-oxygenase (COX). Clinically paracetamol is often used together
      with traditional NSAIDs, which are strong inhibitors of COX. We studied binding
      of paracetamol to COX and its action on platelet function together with
      diclofenac. METHODS: Blood was collected from healthy donors and platelet
      function was assessed by photometric aggregometry, a platelet function analyser
      (PFA-100, Dade Behring, Deerfield, IL) and by measuring the release of
      thromboxane B(2) (TxB(2)), the stable metabolite of thromboxane A(2), after
      addition of paracetamol (10-80 microg ml(-1)). A concentration-inhibition
      relationship was established and the inhibition coefficient (K(i)) demonstrating
      50% binding to COX was determined using a Schild-plot. Interaction of paracetamol
      (5-20 microg ml(-1)) and diclofenac (0.1-0.8 microg ml(-1)) was determined and an
      isobolographic analysis was performed. RESULTS: Paracetamol added to platelet
      rich plasma (PRP) caused a concentration-dependent inhibition of platelet
      function. Photometric aggregometry and TxB(2) release was significantly inhibited
      by paracetamol from 10 microg ml(-1) onwards. The PFA-100 closure time was
      significantly prolonged by paracetamol at a high concentration only. K(i) was
      15.2 microg ml(-1) with a 95% confidence interval of 11.8-18.6 microg ml(-1).
      Inhibition of aggregation by diclofenac was augmented by paracetamol.
      Isobolographic analysis showed synergism. CONCLUSIONS: The 95% confidence
      interval of K(i) equals the antipyretic plasma concentration of paracetamol, i.e.
      10-20 microg ml(-1). High doses of paracetamol and a combination of diclofenac
      and paracetamol cause platelet inhibition and thus may increase risk of surgical
      bleeding.

PMID- 15954970
TI  - Effect of low-dose N-acetyl-cysteine infusion on tourniquet-induced ischaemia
      reperfusion injury in arthroscopic knee surgery.
AB  - BACKGROUND: Temporary occlusion of blood flow is used during arthroscopic knee
      surgery in order to provide a bloodless surgical field. The resulting ischaemia
      reperfusion causes lipid peroxidation, which contributes to tissue injury. The
      aim of the study was to investigate the effect of low-dose n-acetyl cysteine
      (NAC) infusion on oxidative stress by determining malondialdehyde (MDA) levels
      during arthroscopic knee surgery. METHODS: Thirty patients, ASA I - II,
      undergoing arthroscopic knee debridement under a tourniquet were divided into NAC
      and control groups. Anaesthesia was induced with propofol, fentanyl and
      vecuronium bromide and maintained with desflurane in an equal parts O(2)-N(2)O
      mixture. In the NAC group, an infusion of NAC, 5 mg kg(-1).h(-1), was started
      after intubation, and continued until extubation. An equal volume of saline was
      infused to the control group. Duration of ischaemia, anaesthesia time, total dose
      of NAC infused were also recorded. Venous blood and synovial membrane tissue
      samples were obtained 10 min after the onset of NAC infusion but before
      tourniquet inflation (t1), after 30 min of ischaemia (t2), and after 5 min of
      reperfusion following tourniquet release (t3). RESULTS: Plasma MDA levels were
      significantly lower in the NAC group on reperfusion. There were no differences
      between the groups in tissue MDA levels at ischaemia and reperfusion times.
      CONCLUSION: Low-dose n-acetyl cysteine infusion attenuates lipid peroxidation and
      ischaemia-reperfusion injury in arthroscopic knee surgery requiring tourniquet
      application.

PMID- 15954971
TI  - Comparison of the effects of isoflurane and sevoflurane on protein tyrosine
      phosphorylation-mediated vascular contraction.
AB  - BACKGROUND: Isoflurane induces greater effects on vasodilation and decreasing
      blood pressure than sevoflurane. Tyrosine kinase-catalyzed protein tyrosine
      phosphorylation plays an important role in regulating vascular smooth muscle
      contraction. The aim of the present study was to compare the effects of
      isoflurane and sevoflurane on tyrosine phosphorylation-mediated vascular
      constriction, by assessing the degree of sodium orthovanadate (Na(3)VO(4),
      tyrosine phosphatase inhibitor)-induced contraction and protein tyrosine
      phosphorylation of rat aortic smooth muscle. METHODS: Na(3)VO(4)-induced
      contraction and protein tyrosine phosphorylation of rat aortic smooth muscle were
      measured in the presence of genistein, a tyrosine kinase inhibitor, and different
      concentrations of isoflurane and sevoflurane, using isometric force measurement
      and Western blot, respectively. RESULTS: Na(3)VO(4) (10(-4) M) induced sustained
      contraction and tyrosine phosphorylation of substrates that were both markedly
      attenuated in the presence of genistein (5 x 10(-5) M). Isoflurane and
      sevoflurane dose-dependently (1, 2, 3 MAC) attenuated the Na(3)VO(4)-induced
      contraction (P < 0.05-0.005, n = 8), with a greater degree of inhibition by
      isoflurane than sevoflurane at 2 MAC (P < 0.01) and 3 MAC (P < 0.05). Both
      anesthetics also attenuated the total band density of the Na(3)VO(4)-induced,
      tyrosine-phosphorylated substrates in a concentration-dependent manner (P < 0.05
      0.005, n = 4), with much greater attenuation by isoflurane than sevoflurane at 1
      and 2 MAC (P < 0.05), respectively. CONCLUSION: The results of the present study
      demonstrate that isoflurane exhibits a greater degree of inhibition on the
      Na(3)VO(4)-stimulated contraction and protein tyrosine phosphorylation of rat
      aortic smooth muscle compared with sevoflurane. These findings suggest that
      isoflurane depresses the protein tyrosine phosphorylation-mediated contraction of
      vascular smooth muscle to a greater degree than sevoflurane.

PMID- 15954972
TI  - Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and
      creatine kinase in critically ill patients with rhabdomyolysis.
AB  - BACKGROUND: (I) To investigate the kinetics of the myoglobin and creatine kinase
      (CK) in rhabdomyolysis. Especially to describe those patients in whom an isolated
      increase in the myoglobin or the CK occurred at a later stage. (II) To evaluate
      the sensitivity of the myoglobin and the CK as prognostic tools for the
      development of Acute renal failure (ARF). (III) To investigate the effect of
      continuous venovenous haemodiafiltration (CVVHDF) on the myoglobin elimination in
      ARF. PATIENTS AND METHODS: Prospective and retrospective cohort study carried out
      in an ICU of a university hospital. A total of 47 critically ill patients with
      rhabdomyolysis and a plasma myoglobin > 5000 microg l(-1) were admitted between
      July 1998 and July 2003. RESULTS: (I) The myoglobin peaked 0.66 +/- 0.6 days
      before the CK. The elimination kinetics of the myoglobin was faster than for the
      CK. (II) Fifty percent developed ARF. Mortality in the ARF patients was 52%
      compared to 14% in the non-ARF patients. The sensitivity and specificity of
      developing ARF were higher with the myoglobin in comparison to the CK. (III) In
      non-ARF, t(1/2) CK was 25.5 h and t(1/2) myoglobin was 17 h (13-23). In those
      with ARF treated with CVVHDF, t(1/2) CK was 24.8 and t(1/2) myoglobin was 21 h
      (17-29). CONCLUSION: (I) The myoglobin peaked earlier than the CK. (II) The
      myoglobin was a better prognostic tool than the CK. However, the myoglobin also
      has a wide interindividual range. (III) Though the myoglobin is eliminated in
      ultrafiltration t(1/2) myoglobin, it was not faster in patients with ARF treated
      with CVVHDF compared to non-ARF patients.

PMID- 15954973
TI  - Randomized, double-blind study comparing postoperative effects of treatment
      timing with histamine H-receptor antagonist cimetidine.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of timing of
      preoperative, postoperative, and placebo administration of the H(2)-antagonist
      cimetidine on postoperative pain management and the incidence of side-effects.
      METHODS: One hundred and twenty ASA I to II patients, undergoing major
      gynaecological abdominal surgery, were randomly divided into three groups, and
      received a standardized general anaesthesia. The patients in the preoperative
      ('Pre') group received an intravenous infusion of cimetidine 4 mg kg(-1) prior to
      anaesthesia induction; the postoperative ('Post') group received the same volume
      of normal saline. Postoperatively, the patients in the Post group received an
      intravenous infusion of cimetidine 4 mg kg(-1); the patients in the Pre group
      received the same volume of normal saline. The Control group received the same
      volume of normal saline prior to anaesthesia induction and after the end of
      operation. Postoperatively, all patients were treated with a patient-controlled
      intravenous analgesia system, which was programmed to deliver 1 mg of morphine on
      demand for three consecutive days. RESULTS: Pain intensity, morphine consumption,
      sedation score, and side-effects were recorded and evaluated. We found no
      difference among the three groups with respect to pain intensities, morphine
      usage, sedation scores, and the incidence of nausea, vomiting, pruritus, or
      dizziness. CONCLUSIONS: Our results suggested that neither preoperative nor
      postoperative administration of cimetidine 4 mg kg(-1) provided a pre-emptive or
      preventive analgesic advantage for postoperative pain or morphine consumption,
      and that the use of cimetidine failed to reduce the incidence of nausea or
      vomiting.

PMID- 15954974
TI  - Safety of mixture of morphine with ketamine for postoperative patient-controlled
      analgesia: an audit with 1026 patients.
AB  - BACKGROUND: Adding ketamine to morphine for patient-controlled analgesia (PCA)
      may be useful. However, data on this drug combination have been collected on
      small sample sizes. In order to evaluate the safety of the combination morphine-
      ketamine, we conducted a prospective study on a large patient population.
      METHODS: Patient-controlled analgesia was performed with 1026 patients using
      morphine and ketamine in a dose ratio of 1:1. All patients were treated in the
      ward. Prospectively collected data included incidence of complications and side
      effects, verbal pain scores at rest and during mobilization (0 = no pain to 4 =
      very strong pain), consumption of morphine and ketamine and patient satisfaction
      (0 = very un-satisfied to 3 = very satisfied). RESULTS: The study included 462
      women and 564 men who underwent, on average, 71.8 h (+/-56.1) of PCA. There were
      698 orthopaedic, 160 abdominal, 96 thoracic, 20 vascular, 16 plastic, 15
      neurosurgical, 11 urologic and 10 other surgical procedures. No complication was
      observed. Incidence of side-effects was: 1.2% respiratory depression, 23.5%
      nausea, 6.2% vivid dreams and/or hallucinations, 21.4% sedation and 10.3%
      pruritus. Reasons for discontinuing the PCA were side-effects (7.0%) and other
      (0.5%). Mean pain scores over the whole period were 0.44 (+/-0.54) at rest and
      1.36 (+/-0.62) during mobilization. Mean satisfaction score was 2.52 (+/-0.69).
      CONCLUSION: Patient-controlled analgesia with morphine and ketamine is safe. It
      produces side-effects which, however, are infrequently a reason for discontinuing
      the regimen. It is also associated with low pain scores and high patient
      satisfaction.

PMID- 15954975
TI  - Remifentanil patient-controlled analgesia following cardiac surgery.
AB  - BACKGROUND: Remifentanil is increasingly used as a component of cardiac
      anaesthesia. Following cardiac surgery remifentanil is often substituted for
      alternative opioids on the intensive care unit. We were interested to evaluate
      postoperative continuation of remifentanil in the form of remifentanil patient
      control analgesia (RPCA) for those patients who received intraoperative
      remifentanil. The objectives of this study were to assess the safety, efficacy
      and feasibility of the RPCA. METHODS: Ten patients who received an intravenous
      infusion of remifentanil perioperatively for coronary artery bypass graft surgery
      (CABG) had their remifentanil infusion converted to RPCA following extubation on
      the intensive care unit. Remifentanil patient control analgesia delivered an
      initial background infusion consistent with the infusion rate at extubation and
      with a bolus facility of 50 microg administered over 5 min followed by a 5-min
      lockout. Data collection included sedation and pain scores, respiratory rate,
      arterial blood gases, number of successful/unsuccessful attempts and the
      background infusion rate for each subject over a period of 12 h following
      extubation. RESULTS: The data from nine male and one female patient were analyzed
      by using SPSS11 for Windows. During the study period the patients achieved
      adequate pain control and made more RPCA attempts at lower background infusion
      rates. No episodes of apnoea, SpO(2) less than 95% or a rise in PaCO(2) greater
      than 6.5 kPa were observed. CONCLUSION: Remifentanil patient control analgesia
      with a background infusion was effective and safe for postoperative pain relief
      in this group of spontaneously breathing ICU patients following cardiac surgery.

PMID- 15954976
TI  - Improved resuscitation outcome by EMS systems with earlier and greater use of
      sodium bicarbonate.

PMID- 15954977
TI  - Is halothane epileptogenic?

PMID- 15954978
TI  - Emergency medicine experiences of a Danish anaesthetist.

PMID- 15954979
TI  - Failed gastric tube insertion in the LMA-ProSeal.

PMID- 15954980
TI  - Severe hypokalemia occurring during barbiturate coma therapy in a patient with
      severe acute head injury.

PMID- 15954981
TI  - 'Condition critical (?)': assessing the condition of US critical care.

PMID- 15954982
TI  - A case of unusually prolonged hyperbaric spinal anesthesia.

PMID- 15954985
TI  - Effect of cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca
      ATPase, on skeletal muscles from normal and mdx mice.
AB  - AIM: In this study, we investigated Ca2+ loading by the sarcoplasmic reticulum in
      skeletal muscle from mdx mice, an animal model of human Duchenne's muscular
      dystrophy, at two stages of development: 4 and 11 weeks. METHOD: Experiments were
      conducted on fast- (extensor digitorum longus, EDL) and slow- (soleus) twitch
      muscles expressing different isoforms of Ca2+-ATPase, which is responsible for
      the uptake of Ca2+ by the sarcoplasmic reticulum. RESULTS: In sarcoplasmic
      reticulum vesicles, the ATP-dependent activity and sensitivity to cyclopiazonic
      acid (CPA), an inhibitor of the sarcoplasmic reticulum Ca2+-ATPase, were similar
      in mdx and normal EDL muscle. Furthermore, in chemically-skinned fibres from both
      normal and mdx muscles, the presence of CPA induced a decrease in Ca2+ uptake by
      the sarcoplasmic reticulum. However, the sensitivity to CPA was lower in mdx EDL
      muscle than in normal muscle. In addition, in EDL muscle from 4-week-old mdx
      mice, the expression of the slow Ca2+-pump isoform (SERCA2a) was significantly
      increased, without any accompanying change in slow myosin expression. In
      contrast, the expression and function of the Ca2+-ATPase in mdx soleus muscles at
      4- and 11-weeks of development did not differ from those in age-matched controls.
      CONCLUSION: These findings show that in dystrophic muscle, where the Ca2+
      homeostasis was perturbed, the Ca2+ handling by the sarcoplasmic reticulum was
      altered in fast-twitch muscle, and this was associated with the expression of the
      slow isoform of SERCA. In these muscles, reduced Ca2+ uptake could then
      contribute to an elevated concentration of Ca2+ in the cytosol, and also to Ca2+
      depletion of the sarcoplasmic reticulum.

PMID- 15954986
TI  - Myocardial interstitial choline and glutamate levels during acute myocardial
      ischaemia and local ouabain administration.
AB  - AIM: Noradrenaline (NA) uptake transporters are known to reverse their action
      during acute myocardial ischaemia and to contribute to ischaemia-induced
      myocardial interstitial NA release. By contrast, functional roles of choline and
      glutamate transporters during acute myocardial ischaemia remain to be
      investigated. Because both transporters are driven by the normal Na+ gradient
      across the plasma membrane in a similar manner to NA transporters, the loss of
      Na+ gradient would affect the transporter function, which would in turn alter
      myocardial interstitial choline and glutamate levels. The aim of the present
      study was to examine the effects of acute myocardial ischaemia and the inhibition
      of Na+,K+-ATPase on myocardial interstitial glutamate and choline levels.
      METHODS: In anaesthetized cats, we measured myocardial interstitial glutamate and
      choline levels while inducing acute myocardial ischaemia or inhibiting Na+,K+
      ATPase by local administration of ouabain. RESULTS: The choline level was not
      changed significantly by ischaemia (from 0.93 +/- 0.06 to 0.82 +/- 0.13 microm,
      mean +/- SE, n = 6) and was decreased slightly by ouabain (from 1.30 +/- 0.06 to
      1.05 +/- 0.07 microm, P < 0.05, n = 6). The glutamate level was significantly
      increased from 9.5 +/- 1.9 to 34.7 +/- 6.1 microm by ischaemia (P < 0.01, n = 6)
      and from 8.9 +/- 1.0 to 15.9 +/- 2.3 microm by ouabain (P < 0.05, n = 6).
      Inhibition of glutamate transport by trans-L-pyrrolidine-2,4-dicarboxylate (t
      PDC) suppressed ischaemia- and ouabain-induced glutamate release. CONCLUSION:
      Myocardial interstitial choline level was not increased by acute myocardial
      ischaemia or by Na+,K+-ATPase inhibition. By contrast, myocardial interstitial
      glutamate level was increased by both interventions. The glutamate transporter
      contributed to glutamate release via retrograde transport.

PMID- 15954987
TI  - N-acetylcysteine fails to modulate the in vitro function of sarcoplasmic
      reticulum of diaphragm in the final phase of fatigue.
AB  - AIM: In the present study, we tested the hypothesis whether N-acetylcysteine
      (NAC), a non-specific antioxidant, might influence fatigue by modulating Ca2+
      handling capacity by the sarcoplasmic reticulum (SR). METHODS: In the presence
      (10 mm) or absence of NAC, bundles of rat diaphragm were stimulated with tetanic
      trains (350 ms, 30-40 Hz) at 1 train every 2 s for 300 s. SR functions, as
      assessed by SR Ca2+-uptake and release rates and SR Ca2+-ATPase activity, were
      measured in vitro on muscle homogenates. RESULTS: Following the 300-s
      stimulation, the force developed by NAC-treated muscles is approximately 1.8-fold
      higher (P < 0.05) than that of muscles without NAC treatment. Stimulation
      elicited an 18-30% depression in SR function (P < 0.05). Despite the differing
      degrees of fatigue between NAC-treated and non-treated muscles, SR functions in
      these muscles were reduced to similar extents. CONCLUSIONS: These results suggest
      that modulation of SR function measured in vitro may not be a major contributor
      to inhibition of diaphragmic fatigue with antioxidant, at least, in the final
      phase of fatigue where force output is remarkably reduced.

PMID- 15954988
TI  - Effects of lengthening contraction on calcium kinetics and skeletal muscle
      contractility in humans.
AB  - AIM: We have tested the hypothesis that the altered muscle contractility after
      lengthening contractions (LC) is caused by altered calcium (Ca2+) kinetics.
      METHODS: Subjects (n = 8) performed 100 drop jumps and muscle contractility was
      measured pre- and post-exercise by maximal voluntary contraction (MVC) and
      transcutaneous electrical stimulation (1, 20 and 50 Hz). Muscle biopsies were
      analysed for muscle metabolites, rates of SR Ca(2+) uptake (CaU) and release
      (CaR) and myosin heavy chain (MHC) composition. RESULTS: The rates of torque
      relaxation and CaU were positively related to muscle fibre type composition (%
      MHC II). Muscle creatine (Cr) decreased and the ratio between phosphocreatine
      (PCr) and Cr increased 3 and 24 h post-exercise (P < 0.05 vs. pre-exercise). LC
      resulted in reduced MVC (-19%), twitch torque (-41%) and 20/50 Hz torque ratio (
      30%) and a faster relaxation rate (P < 0.05). The contractile parameters
      recovered partially but remained altered 24 h post-exercise (P < 0.05). The
      average CaR was unchanged after LC (P > 0.05). However, the response varied
      between subjects and the relative post-exercise CaR was significantly related to
      the degree of LFF (post/pre 20/50 Hz force ratio) and to the decline in twitch
      force (post/pre twitch ratio). CaU was lower in seven of eight subjects after LC
      (P > 0.05). CONCLUSION: The decline in torque after LC could not be explained by
      metabolic factors since PCr/Cr ratio increased. The relation between CaR and
      fatigue suggests that the mechanism of fatigue in part may be attributed to
      intrinsic changes in the SR Ca2+ release channel. The faster torque relaxation
      after LC could not be explained by an increased rate of CaU.

PMID- 15954989
TI  - Regulation of oxidative enzyme activity and eukaryotic elongation factor 2 in
      human skeletal muscle: influence of gender and exercise.
AB  - AIM: To investigate gender-related differences in the responses of oxidative
      enzymes and eukaryotic elongation factor-2 (eEF2) to exercise. METHODS: The
      influence of exercise (90 min, 60%VO(2peak)) on citrate synthase (CS) and beta
      hydroxyacyl-CoA dehydrogenase (HAD) activity and mRNA content, together with eEF2
      expression and phosphorylation at rest, were assessed in skeletal muscle of
      untrained (UT) and endurance trained (ET) females and males. RESULTS: Citrate
      synthase and HAD mRNA were higher in females than in males (27% and 48%,
      respectively, P < 0.05) whereas CS and HAD activity did not differ between
      females and males (NS). In females only, CS activity was enhanced (P < 0.05) by
      90 min exercise. Resting CS mRNA content did not differ between UT and ET but,
      nevertheless, CS activity was 56% higher in ET than in UT volunteers (P < 0.001).
      HAD mRNA and activity were not influenced by training status (NS). In UT, CS mRNA
      was enhanced 37% (P < 0.05) by exercise whereas exercise did not change CS mRNA
      in ET (NS). eEF2 expression was 31% higher (P < 0.05) and eEF2 Thr56
      phosphorylation (which leads to translation inhibition) was 24% lower (P < 0.05)
      in females than in males. eEF2 expression and phosphorylation were unaffected by
      training status (NS). CONCLUSION: Basal transcriptional, translational, and/or
      post-translational control of CS and HAD seems to be gender-dependent. Also,
      gender differences in translation and/or post-translational protein modification
      of CS occur during exercise. Accordingly, the potential for peptide-chain
      elongation, based on eEF2 expression and phosphorylation, appears to be higher in
      females than in males.

PMID- 15954990
TI  - Effects of sodium intake on plasma potassium and renin angiotensin aldosterone
      system in conscious dogs.
AB  - AIMS: The operating range of the renin-angiotensin-aldosterone system is ill
      defined. This study quantifies renin-angiotensin-aldosterone system activity as a
      function of sodium intake. METHODS: Renin-angiotensin-aldosterone system
      variables were measured daily after a sudden reduction in sodium intake (3.0-0.5
      mmol kg(-1) day(-1)) or at steady states generated by eight levels of sodium
      intake (0.5-8.0 mmol kg(-1) day(-1)). Potassium intake was 2.79 +/- 0.03 mmol kg(
      1) day(-1). Arterial blood pressure was measured invasively. Hormone
      concentrations were determined by radioimmunoassays. Glomerular filtration rate
      and plasma volume were determined by standard methods. RESULTS: Sudden sodium
      intake reduction doubled plasma renin activity and angiotensin II, and tripled
      aldosterone on day 1 with only small non-significant additional changes on the
      following days. Different levels of sodium intake did not affect arterial blood
      pressure, heart rate, and plasma concentrations of sodium, angiotensinogen,
      atrial natriuretic peptide, vasopressin, glomerular filtration rate and diuresis.
      With increasing sodium intake, plasma volume increased by 0.47 +/- 0.04 mL (kg
      body mass)(-1) (unit increase in Na intake)(-1) (P < 0.01), and plasma potassium
      decreased with the slope -0.038 mm [(mmol Na+ intake) (kg body mass)(-1) day(
      1)](-1) (P = 0.001) while plasma renin-activity, angiotensin II, and aldosterone
      decreased systematically as expected. CONCLUSIONS: A step reduction in sodium
      intake alters renin-angiotensin-aldosterone system activity on day 1 with little
      further change the subsequent 4 days. Week-long increases in sodium intake
      decreases renin-angiotensin-aldosterone system activity, increases plasma volume,
      and decreases plasma potassium. Isolated decreases in sodium intake increase
      aldosterone secretion via volume-mediated action on the renin-angiotensin system
      and via increases in plasma potassium.

PMID- 15954991
TI  - Skeletal muscle contractility is preserved in COPD patients with normal fat-free
      mass.
AB  - AIM: Peripheral muscle dysfunction often occurs in patients with chronic
      obstructive pulmonary disease (COPD). The muscle dysfunction may be caused by a
      loss of force-generating capacity, resulting from a loss of muscle mass, as well
      as by other alterations in contractile properties of skeletal muscle. METHODS:
      The maximal isometric voluntary strength and fatigability were determined in hand
      grip and quadriceps muscles from nine male COPD patients (FEV(1) 30-50%
      predicted) and control subjects matched for fat-free mass (FFM), physical
      activity level and age. Contractile properties and fatigability of the quadriceps
      muscle were also studied with electrically evoked isometric contractions.
      RESULTS: The maximal voluntary force (MVC) and fatigability of the handgrip
      muscle did not differ between the COPD patients and control subjects. Also the
      MVC of the quadriceps muscle and the rate of force rise, contraction time, force
      frequency relationship and fatigability, as determined with electrically evoked
      contractions, were similar in patients with COPD and control subjects.
      CONCLUSION: Skeletal muscle strength, contractile properties and fatigability are
      preserved in patients with moderate COPD and a normal FFM and activity level.
      This suggests that skeletal muscle dysfunction does not take place during
      moderate COPD until cachexia and/or a decline in physical activity occur.

PMID- 15954992
TI  - Nitrite transport into pig erythrocytes and its potential biological role.
AB  - AIM: To study nitrite transport and its oxygenation dependency in pig
      erythrocytes, as this is fundamental to the possible participation of nitrite in
      blood flow regulation via its reduction to nitric oxide by deoxygenated
      haemoglobin (Hb). METHODS: Pig red blood cells (RBCs) were tonometer-equilibrated
      to physiological pCO2 in oxygenated and deoxygenated states. Nitrite was added
      and the kinetics of NO2- influx and methaemoglobin (metHb) formation were
      assessed at variable temperature and haematocrit. RESULTS: Nitrite quickly
      permeated and equilibrated across the membrane, and then continued to enter RBCs
      as a consequence of its intracellular removal (via reactions with Hb to form
      nitrate and metHb in oxygenated cells, and NO and metHb in deoxygenated cells).
      The membrane permeation as such showed little oxygenation dependency, but as
      metHb formation was significantly higher in oxygenated than deoxygenated RBCs,
      nitrite transport tended to be largest into oxygenated RBCs. This contrasts with
      a preferential permeation of deoxygenated RBCs in some fish species. Nitrite
      transport showed low temperature sensitivity but was speeded up at low
      haematocrit via more rapid intracellular nitrite removal (metHb formation).
      Nitrite influx was not affected by inhibitors of facilitated diffusion (DIDS,
      phloretin and PCMB) and may occur via conductive transport. Extracellular pH was
      stable during nitrite transport. CONCLUSION: Nitrite extensively permeates both
      oxygenated and deoxygenated pig RBCs, which may enable a dual function of nitrite
      entry: viz. conversion to NO at low pO2 to promote blood flow and detoxification
      to non-toxic nitrate at inappropriate high nitrite levels.

PMID- 15954993
TI  - Drinking volume and patterns: back to basics.

PMID- 15954994
TI  - Cannabis potency in Europe.

PMID- 15954996
TI  - Banning smoking in taverns and restaurants--a research opportunity as well as a
      gain for public health.

PMID- 15954997
TI  - Australia and alcohol: living down the legend.

PMID- 15954998
TI  - Conversation with Elisaldo Luiz de Araujo Carlini (E. A. Carlini).

PMID- 15954999
TI  - Effects of a sustained heroin shortage in three Australian States.
AB  - BACKGROUND: In early 2001 in Australia there was a sudden and dramatic decrease
      in heroin availability that occurred throughout the country that was evidenced by
      marked increases in heroin price and decreases in its purity. AIM: This study
      examines the impact of this change in heroin supply on the following indicators
      of heroin use: fatal and non-fatal drug overdoses; treatment seeking for heroin
      dependence; injecting drug use; drug-specific offences; and general property
      offences. The study was conducted using data from three Australian States [New
      South Wales (NSW), Victoria (VIC) and South Australia (SA)]. METHODS: Data were
      obtained on fatal and non-fatal overdoses from hospital emergency departments
      (EDs), ambulance services and coronial systems; treatment entries for heroin
      dependence compiled by State health departments; numbers of needles and syringes
      distributed to drug users; and data on arrests for heroin-related incidents and
      property-related crime incidents compiled by State Police Services. Time-series
      analyses were conducted where possible to examine changes before and after the
      onset of the heroin shortage. These were supplemented with information drawn from
      studies involving interviews with injecting drug users. RESULTS: After the
      reduction in heroin supply, fatal and non-fatal heroin overdoses decreased by
      between 40% and 85%. Despite some evidence of increased cocaine, methamphetamine
      and benzodiazepine use and reports of increases in harms related to their use,
      there were no increases recorded in the number of either non-fatal overdoses or
      deaths related to these drugs. There was a sustained decline in injecting drug
      use in NSW and VIC, as indicated by a substantial drop in the number of needles
      and syringes distributed (to 1999 levels in Victoria). There was a short-lived
      increase in property crime in NSW followed by a sustained reduction in such
      offences. SA and VIC did not show any marked change in the categories of property
      crime examined in the study. CONCLUSIONS: Substantial reductions in heroin
      availability have not occurred often, but in this Australian case a reduction had
      an aggregate positive impact in that it was associated with: reduced fatal and
      non-fatal heroin overdoses; reduced the apparent extent of injecting drug use in
      VIC and NSW; and may have contributed to reduced crime in NSW. All these changes
      provide substantial benefits to the community and some to heroin users.
      Documented shifts to other forms of drug use did not appear sufficient to produce
      increases in deaths, non-fatal overdoses or treatment seeking related to those
      drugs.

PMID- 15955000
TI  - Learning from uncommon events: comment on Degenhardt et al. 2005.

PMID- 15955001
TI  - More panic in needle park.

PMID- 15955002
TI  - Avoiding simplistic interpretations: comment on Degenhardt et al. 2005.

PMID- 15955003
TI  - Availability as a law of addiction.

PMID- 15955004
TI  - Heroin, supply side interventions and crime.

PMID- 15955005
TI  - Supply control does work: the case from Australia.

PMID- 15955006
TI  - Supply control policy, harm reduction and context dependence.

PMID- 15955007
TI  - The benefits of structural modeling of the Australian heroin drought.

PMID- 15955009
TI  - Drinking patterns, drinking contexts and alcohol-related aggression among late
      adolescent and young adult drinkers.
AB  - AIMS: The main objectives of this study were to determine: (1) the relative roles
      of heavy episodic drinking (HED), drinking frequency and drinking volume in
      explaining alcohol-related aggression and (2) whether drinking context variables
      (i.e. usual drinking locations, typical drinking companions and extent of peer
      drinking) confound or modify the relationship between HED and alcohol-related
      aggression or whether they predict alcohol-related aggression independently.
      DESIGN: A secondary analysis of the US National Longitudinal Survey of Youth was
      conducted. Alcohol-related aggression (denoted fights after drinking) was
      measured based on self-reports of arguments or fights that occurred during or
      after drinking in the previous 12 months. PARTICIPANTS: A composite sample of
      drinkers, ages 17-21, from the 1994, 1996 and 1998 Young Adult surveys (n = 738)
      was used. FINDINGS: Frequency of drinking and drinking volume largely confounded
      the association between HED and fights after drinking. Usually drinking in public
      locations away from home versus private locations was found to be significantly
      associated with a greater likelihood of fights after drinking among females.
      Among males, usual drinking location modified the relationship between drinking
      frequency and alcohol-related aggression, with the greatest risk of aggression
      for males who drank frequently and usually drank in public locations away from
      home. CONCLUSIONS: Programs designed to reduce drinking frequency in this
      population and to increase the safety of drinking locations in public places away
      from home may prove to be beneficial in reducing alcohol-related aggression.

PMID- 15955010
TI  - Level of impaired control predicts outcome of moderation-oriented treatment for
      alcohol problems.
AB  - AIMS: To examine the ability of the Impaired Control Scale (ICS) to predict
      outcome of moderation-oriented treatment for alcohol problems and to compare this
      predictive ability directly with that of a widely used measure of alcohol
      dependence, the Severity of Alcohol Dependence Questionnaire (SADQ). DESIGN:
      Prospective follow-up study. SETTING: Out-patient treatment centres.
      PARTICIPANTS: A combined sample 154 problem drinkers taking part in two clinical
      trials of Moderation-oriented Cue Exposure in the UK and Australia. Clients were
      followed-up 6 (UK) and 8 (Australia) months after the end of treatment.
      MEASUREMENTS: Outcome was categorized by combining drinking behaviour at follow
      up with changes on the Alcohol Problems Questionnaire from before treatment to
      follow-up. Controlling for research site, baseline scores on Part 2 of the ICS
      (substitution method) and the SADQ-C were entered in logistic regression analyses
      with three outcome dichotomies as dependent variables. FINDINGS: Five per cent of
      clients were abstinent at follow-up, 13% non-problem drinkers, 25% much improved,
      24% somewhat improved and 34% unimproved. Location of treatment and ICS2 scores
      were significant predictors of whether or not clients achieved a successful
      outcome (abstinence or non-problem drinking). Using a cut-point of 25 on the ICS,
      two-thirds of outcomes were classified correctly as either treatment successes or
      failures. SADQ-C score was not a significant predictor of treatment outcome.
      CONCLUSIONS: The ICS predicts outcome of moderation-oriented treatment among
      moderately dependent problem drinkers recruited mainly via newspaper
      advertisements. The ICS should replace the SADQ as the basis for advice to
      clients in this population of problem drinkers regarding whether or not a
      moderation goal of treatment should be pursued.

PMID- 15955011
TI  - Alcohol expectancies, conduct disorder and early-onset alcoholism: negative
      alcohol expectancies are associated with less drinking in non-impulsive versus
      impulsive subjects.
AB  - AIMS: Research suggests that positive alcohol expectancies promote excessive
      alcohol use while negative alcohol expectancies discourage excessive alcohol use.
      Evidence suggests that disinhibitory characteristics, such as conduct disorder
      and impulsivity, are associated with a general neglect of long-term negative
      outcomes. This study assessed whether negative expectancies would be associated
      more strongly with lower levels of alcohol use for low- compared with high
      impulsive individuals. DESIGN: Positive and negative alcohol expectancies,
      alcohol use and impulsivity were assessed in a sample of 99 young adults with
      alcohol dependence (AD) and conduct disorder (CD), 77 with AD and no CD and 124
      controls. FINDINGS: AD/CD subjects had higher proximal (same day) and distal
      (next day) negative alcohol expectancies, even though they drank more alcohol,
      compared with AD-alone and control subjects. Distal negative expectancies were
      associated more strongly with lower levels of drinking for low-impulsive compared
      with high-impulsive subjects. Proximal negative expectancies were associated more
      strongly with higher alcohol consumption for high- versus low-impulsive subjects.
      CONCLUSIONS: Impulsivity and conduct disorder may be important factors in
      determining how much distal negative alcohol expectancies may discourage
      excessive alcohol consumption.

PMID- 15955012
TI  - First cannabis use: does onset shift to younger ages? Findings from 1988 to 2003
      from the Dutch National School Survey on Substance Use.
AB  - AIMS: To investigate the hypothesis that changes in cannabis prevalence among
      Dutch secondary school students (aged 12-17 years) were paralleled by shifts in
      the age of first cannabis use. DESIGN AND PARTICIPANTS: Data were derived from
      five waves (1988, 1992, 1996, 1999 and 2003) of the Dutch National School Survey
      on Substance Use, a nationally representative cross-sectional study, with a total
      of 32,777 respondents. MEASUREMENTS: Written questionnaires on cannabis, tobacco,
      alcohol, other drug use and socio-demographic and behavioural variables were
      administered in classroom settings. FINDINGS: Survival analysis showed a strong
      increase in cumulative incidences by age of first cannabis use from 1988 to 1992,
      a further increase in 1996 and stabilization in 1999, continuing into 2003. From
      1992 to 1996, age of onset shifted towards younger ages. Onset peaked at age 15
      in 1992 and age 14 in 1996. The proportion of life-time cannabis users starting
      at age 13 or younger increased from 26% in 1992 to 41% in 1996. The overall trend
      was similar for boys and girls. CONCLUSIONS: The study largely confirmed the
      expectation that the increase in cannabis use from 1988 to 1996 was paralleled by
      a decrease in the age of first cannabis use. From 1996 to 2003 age of first
      cannabis use and prevalence stabilized, possibly occasioned by a change in
      cannabis policy in the mid-1990s.

PMID- 15955013
TI  - Cannabis 'tinny' houses in New Zealand: implications for the use and sale of
      cannabis and other illicit drugs in New Zealand.
AB  - AIM: To examine the impact of the emergence of cannabis 'tinny' houses on the use
      and sale of cannabis and other illicit drugs in New Zealand. METHOD: A national
      sample of 5800 people aged 13-45 years were interviewed about their drug use
      using a computer-assisted telephone interview (CATI) system as part of the 2001
      National Drug Survey. A question on cannabis procurement was used to create two
      subgroups of cannabis buyers for further analysis: (i) 'tinny' house buyers-
      those who had purchased 'some', 'most' or 'all' of their cannabis from a 'tinny'
      house (n = 145) and (ii) personal market buyers--those who had purchased 'none'
      or 'hardly any' of their cannabis from a 'tinny' house (n = 342). The two groups
      of cannabis buyers were compared for a range of variables. ['Tinny' houses are
      residential properties converted for the 'supermarket' sale of cannabis and other
      illicit drugs to anyone who attends the premises with cash.] FINDINGS: Those
      purchasing cannabis from 'tinny' houses were significantly more likely than those
      purchasing cannabis from the personal market to smoke one joint or more on a
      typical occasion, to purchase cannabis weekly or more often, to purchase small
      weights of cannabis, to be sold lower quality cannabis than they paid for, to
      know their cannabis dealer sells other illicit drug types and to use high potency
      strains of cannabis. There was no significant difference between the 'tinny'
      house and personal market cannabis buyers with respect to the frequency of
      cannabis use, prices paid for the same weights of cannabis, levels of other
      victimization, levels of other drug use or levels of encouragement by cannabis
      sellers to purchase other drug types. Those purchasing cannabis from 'tinny'
      houses were more likely to be aged 15-17 years old and to be of Maori ethnicity
      than those purchasing cannabis from the personal market. CONCLUSION: Cannabis
      'tinny' houses attracted more adolescent and more Maori clientele. However,
      'tinny' houses did not appear to be contributing to the spread of the use of
      other drug types either through the active marketing of other drugs or by having
      these drugs available for sale at these locations.

PMID- 15955014
TI  - Evaluating the impact of methadone maintenance programmes on mortality due to
      overdose and aids in a cohort of heroin users in Spain.
AB  - AIMS: To assess the relationship between methadone treatment (MT) and overdose
      and HIV/AIDS mortality among heroin users resident in Barcelona city. DESIGN: All
      patients who started treatment in any treatment centre between 1992 and 1997 were
      included in a cohort the first time they were admitted for heroin addiction
      treatment. Follow-up controls were carried out every 9 months, on average, until
      31 December 1999. Variables, both constant and varying over time, were fitted
      into Cox regression models. FINDINGS: The study recruited 5049 patients, which
      provided 23,048.2 person-years. Fifty per cent were in MT during the study
      period; of the total cohort 1005 patients died: 38.4% due to AIDS, 34.7% to
      overdose and 27% to other causes. Overall mortality decreased from 5.9 deaths per
      100 person-years in 1992 to 1.6 in 1999. Globally, life expectancy at birth was
      39 years, 38 years lower than that of the general population. The main factor for
      overdose mortality was not being in MT at the time of death [relative ratio (RR)
      = 7.1]; other factors were being a current injector at baseline and being HIV
      positive. For AIDS mortality, the main factor was the calendar year (RR for 1996
      versus 1999 = 4.6), the next major factor was more than 10 years of heroin
      consumption, followed by not being in MT, being unemployed, then having a prison
      record. CONCLUSIONS: The observed mortality decline could be linked to the
      effectiveness of low-threshold MT. The life expectancy of heroin users increased
      by 21 years during the study period.

PMID- 15955015
TI  - The relationship between non-injection drug use behaviors on progression to AIDS
      and death in a cohort of HIV seropositive women in the era of highly active
      antiretroviral therapy use.
AB  - AIMS: To evaluate the effects of longitudinal patterns and types of non-injection
      drug use (NIDU) on HIV progression in the highly active antiretroviral therapy
      (HAART) era. DESIGN: Women's Interagency HIV Study (WIHS), a prospective cohort
      study conducted at six US sites. METHODS: Data were collected semi-annually from
      1994 to 2002 on 1046 HIV(+) women. Multivariate Cox proportional hazards modeling
      was used to estimate relative hazards for developing AIDS and for death by
      pattern and type of NIDU. FINDINGS: During follow-up, 285 AIDS events and 287
      deaths, of which 177 were AIDS-related, were reported. At baseline, consistent
      and former NIDU was associated with CD4(+) counts of < 200 cells/microl (43% and
      46%, respectively) and viral load > 40,000 copies/ml (53% and 55%, respectively).
      Consistent NIDU reported less HAART use (53%) compared with other NIDU patterns.
      Stimulant use was associated with CD4(+) cell counts of < 200 cells/microl (53%)
      and lower HAART initiation (63%) compared with other NIDU types. In multivariate
      analyses, progression to AIDS was significantly higher among consistent (RH =
      2.52), inconsistent (RH = 1.63) and former (RH = 1.56) users compared with never
      users; and for stimulant (RH = 2.04) and polydrug (RH = 1.65) users compared with
      non-users. Progression to all-cause death was higher only among former users (RH
      = 1.48) compared with never users in multivariate analysis. NIDU behaviors were
      not associated with progression to AIDS-related death. CONCLUSIONS: In this
      study, pattern and type of NIDU were associated with HIV progression to AIDS and
      all-cause mortality. These differences were associated with lower HAART
      utilization among consistent NIDU and use of stimulants, and poor baseline
      immunological and virological status among former users.

PMID- 15955016
TI  - Depressive symptoms and smoking among Hong Kong Chinese adolescents.
AB  - AIMS: To examine associations among depressive symptoms, smoking, smoking
      trajectories and quitting smoking in Hong Kong. DESIGN: Prospective longitudinal
      design, with wave 1 at baseline (T1) and wave 2 (T2) 12 months later. SETTING AND
      PARTICIPANTS: Form 1 (equivalent to 7th grade in the United States) students,
      mean age = 12.7 years, n = 1894. MEASUREMENTS: Self-reported smoking status,
      attempts to quit and depressive symptoms. FINDINGS: At both waves, current as
      well as ex-smokers had higher depressive symptoms than never smokers. T1 smoking
      predicted T2 depressive symptoms among those with low baseline depressive
      symptoms. Depressive symptoms at T1 predicted smoking at T2 among non-smokers at
      T1. Trajectories were defined by separating participants who were never smokers
      at both waves ('non-smokers'), those who smoked at both waves ('persistent
      smokers'), those who smoked at one time but were not smoking at either wave
      ('past smokers), and those who had never smoked at T1 but reported smoking a year
      later ('new smokers'). Persistent, past and new smokers had higher depressive
      symptoms at both waves than non-smokers. Smokers who reported not wanting or
      trying to quit and those who had been unsuccessful at quitting had higher
      depressive symptoms at T2 than those who successfully quit. CONCLUSION: Our
      results suggest that depressive symptoms promote tobacco use in Asian adolescents
      by making it more likely that an adolescent will begin smoking and less likely
      that she or he will quit. These findings elucidate risk factors in Hong Kong for
      two important public health concerns for adolescents: smoking and depression.

PMID- 15955017
TI  - Reimbursement for smoking cessation treatment may double the abstinence rate:
      results of a randomized trial.
AB  - AIMS: Few smokers who try to quit smoking use smoking cessation treatment (SCT),
      and cost could be one factor. To increase the number of successful quitters, we
      assessed whether financial reimbursement for SCT would encourage the use of SCT
      and would as a result increase the 6-month point abstinence rate. SETTING AND
      PARTICIPANTS: We recruited smokers aged over 18 years from a random sample of
      Dutch inhabitants insured by one health insurance company. INTERVENTION AND
      DESIGN: The smokers were assigned randomly to the intervention group (n = 632) or
      control group (n = 634). Respondents in the intervention group received an offer
      of reimbursement for nicotine replacement therapy, bupropion and behavioural
      counselling. No reimbursement was offered to the control group. To preclude a
      change of behaviour due to disappointment in the control group, we used a
      randomized consent design. FINDINGS: During the reimbursement period, 10.8%
      smokers in the intervention group reported having used SCT compared with 4.1% in
      the control group (OR = 2.9, 95% CI 1.8-4.7). In the intervention group, 23.4%
      smokers tried to stop compared with 20.8% in the control group (OR = 1.2, 95% CI
      0.9-2.4). After 6 months, the biochemically validated 7-day point prevalence
      abstinence rate was 5.5% in the intervention group and 2.8% in the control group
      (OR = 2.3, 95% CI 1.2-4.1). CONCLUSIONS: Reimbursement for SCT seems efficacious
      in increasing the use of SCT and may double the number of successful quitters.

PMID- 15955018
TI  - Smoking habits and obesity in young adults.
AB  - AIMS: The aim of this work was to study the association between obesity and
      smoking habits in young adults. Specifically, we tested the hypothesis that
      obesity does not prevent young adults from smoking and conversely smoking does
      not protect against obesity. DESIGN AND SETTING: Trained nurses interviewed
      participants concerning demographic data and health behaviors such as smoking. At
      the time of the interview, weight and height were measured. Data were analyzed
      retrospectively. PARTICIPANTS: A representative sample of Israel Defense Force
      (IDF) personnel upon discharge from compulsory service, usually at the age of 20
      21 years. FINDINGS: Overall, 29 745 participants were included during the 13-year
      study (16,363 males and 13,382 females). Smoking rates were higher among obese
      participants than among overweight and non-obese participants (34.9%, 37.1%,
      43.6% for non-obese, overweight and obese, respectively; P < 0.001). Mean number
      of cigarettes smoked per day were also higher among smokers that were obese and
      overweight compared to the non-obese (15.2 +/- 9.2, 15.6 +/- 10.7, 18.0 +/- 9.8,
      respectively; P < 0.001). Overweight and obesity were associated with the
      father's lower academic educational level. In logistic regression analysis,
      obesity, year of study and parental academic education were correlated
      independently with smoking (P < 0.001). CONCLUSION: The positive association
      between obesity and smoking suggests that obesity is not a deterrent to smoking
      and also that smoking does not help to prevent obesity.

PMID- 15955019
TI  - A comment on allowing saturday sales in the Swedish retail monopoly.

PMID- 15955020
TI  - Blame the counselling, not the implant. A response to Oliver, Horspool & Keen
      (2005).

PMID- 15955021
TI  - Driving capacity of patients treated with methadone and slow-release oral
      morphine.

PMID- 15955027
TI  - The effects of apigenin-7-O-beta-D-glucuronopyranoside on reflux oesophagitis and
      gastritis in rats.
AB  - 1. This study evaluated the inhibitory action of apigenin-7-O-beta-D
      glucuronopyranoside (AGC), apigenin, and omeprazole on reflux oesophagitis and
      gastritis in rats. AGC was isolated from Clerodendron trichotomum leaves. 2.
      Oesophagitis and gastritis were induced by surgical procedure and the
      administration of indomethacin, respectively. The intraduodenal (i.d.)
      administration of AGC decreased the volume of gastric juice and increased the
      gastric pH compared with apigenin and omeprazole. The acid output was more
      inhibited by AGC in a dose-dependent manner than by apigenin and omeprazole.
      Compared with apigenin and omeprazole, AGC significantly decreased the size of
      gastric lesions, which were induced by exposure of the gastric mucosa to
      indomethacin. 3. Malondialdehyde (MDA) content, which is the end product of lipid
      peroxidation, was increased significantly after the induction of reflux
      oesophagitis. The MDA content was decreased by AGC (i.d. 3 mg kg(-1)), but not by
      either apigenin or omeprazole. This suggests that AGC has an antioxidative
      effect. In the oesophagitis group, the mucosal levels of glutathione (GSH) were
      significantly lower than that in the normal group. However, the GSH levels were
      preserved after administering the AGC, suggesting that AGC possesses scavenging
      activity. 4. In summary, AGC is more potent than apigenin and omeprazole at
      inhibiting reflux oesophagitis and gastritis and may therefore be a promising
      drug for their treatment.

PMID- 15955028
TI  - Neuronal nitric oxide synthase activity in rat urinary bladder detrusor:
      participation in M3 and M4 muscarinic receptor function.
AB  - 1. The aim of this paper was to determine the different signalling cascades
      involved in contraction of the rat urinary bladder detrusor muscle mediated via
      muscarinic acetylcholine receptors (muscarinic AChR). Contractile responses,
      phosphoinositides (IPs) accumulation, nitric oxide synthase (NOS) activity and
      cyclic GMP (cGMP) production were measured to determine the reactions associated
      with the effect of cholinergic agonist carbachol. The specific muscarinic AChR
      subtype antagonists and different inhibitors of the enzymatic pathways involved
      in muscarinic receptor-dependent activation of NOS and cGMP were tested. 2.
      Carbachol stimulation of M(3) and M(4) muscarinic AChR increased contractility,
      IPs accumulation, NOS activity and cGMP production. All of these effects were
      selectively blunted by 4-DAMP and tropicamide, M(3) and M(4) antagonists
      respectively. 3. The inhibitors of phospholipase C (PLC), calcium/calmodulin
      (CaM), neuronal NOS (nNOS) and soluble guanylate cyclase, but not of protein
      kinase C and endothelial NOS (eNOS), inhibited the carbachol action on detrusor
      contractility. These inhibitors also attenuated the muscarinic receptor-dependent
      increase in cGMP and activation of NOS. 4. In addition, sodium nitroprusside and
      8-bromo-cGMP, induced negative relaxant effect. 5. The results obtained suggest
      that carbachol activation of M(3) and M(4) muscarinic AChRs, exerts a contractile
      effect on rat detrusor that is accompanied by an increased production of cGMP and
      nNOS activity. The mechanism appears to occur secondarily to stimulation of IPs
      turnover via PLC activation. This in turn, triggers cascade reactions involving
      CaM, leading to activation of nNOS and soluble guanylate cyclase. They, in turn,
      exert a modulator inhibitory cGMP-mediated mechanism limiting the effect of
      muscarinic AChR stimulation of the bladder.

PMID- 15955029
TI  - Postjunctional alpha1-adrenoceptors in the vasculature of the pithed mouse are of
      the alpha1A-subtype.
AB  - 1. The pressor action of noradrenaline and its blockade by selective alpha(1)
      adrenoceptor antagonists in the pithed mouse were evaluated. 2.
      Chloroethylclonidine (alpha(1B/D)-adrenoceptor alkylating agent) or BMY 7378
      (alpha(1D)-adrenoceptor antagonist), both at 1 mg kg(-1), did not block the
      increase in blood pressure induced by noradrenaline. 3. 5-Methylurapidil
      (alpha(1A)-adrenoceptor antagonist), at 0.1 mg kg(-1), displaced the dose
      response curve approximately six-fold to the right. 4. The results support the
      idea that the pithed mouse vasculature express alpha(1A)-adrenoceptors and
      suggest that it is a good model to study the roles of alpha(1)-adrenoceptors in
      gene knockout or overexpression.

PMID- 15955030
TI  - Differential effects of nifedipine and verapamil on non-adrenergic non
      cholinergic relaxations at different levels of active tone: assessment of the
      contribution of nerve-derived hyperpolarizing factor.
AB  - 1. The objective was to investigate a possible contribution of a nerve-derived
      hyperpolarizing factor to the differences between non-adrenergic non-cholinergic
      (NANC) nerve-mediated relaxations in different states of active tone in the rat
      gastric fundus. 2. NANC relaxations induced by electrical field stimulation (ES:
      0.1, 0.5 and 1 Hz; 25 V; 1 ms; 10 s) in 40% contracted strips (S40) were greater
      when compared with those in 80% contracted strips (S80). 3. ES-induced
      relaxations were effectively attenuated by N(omega)-nitro-L-arginine (L-NNA; 100
      microm) in S40 and S80. Percentage reduction of the responses obtained in the
      presence of L-NNA in S40 group was less than that of S80. 4. In S40 group,
      nifedipine (0.5-1 microm) and verapamil (0.5-1 microm) inhibited the responses to
      0.1 and 0.5 Hz. Nifedipine (1 microm) and verapamil (0.5 microm) caused no change
      in the responses to ES in S80. 5. In S40, when L-NNA (100 microm) and nifedipine
      or verapamil, either in 1 microm concentration, were administered together, the
      inhibition on the electrical relaxations were more than that of each drug alone.
      6. In conclusion, NANC nerve-mediated relaxations are increased when studied in
      an active state of 40%, and a factor, sensitive to nifedipine seems to be
      responsible for this distinction.

PMID- 15955031
TI  - Postjunctional modulation by muscarinic M2 receptors of responses to electrical
      field stimulation of rat detrusor muscle preparations.
AB  - 1. The aim of the present study was to examine the modulator influence of
      muscarinic M(2) receptors on responses of rat urinary bladder detrusor muscle
      evoked by endogenous stimuli, i.e. by stimulation of the bladder innervation. 2.
      Responses were evoked by electrical field stimulation (EFS; 2-20 Hz, 0.8 ms, 60
      V) of isolated strip preparations mounted in organ baths. The tension of the
      muscle strips was recorded digitally. EFS was performed by applying stimulation
      with either a short duration (5 s) or a longer duration (to reach peak response;
      approximately 20 s). 3. Effects of muscarinic receptor antagonists (muscarinic
      M(1)/M(3) receptor selective: 4-diphenylacetoxy-N-methylpiperidine methobromide
      (4-DAMP); muscarinic M(2) receptor selective: methoctramine), a beta-adrenergic
      antagonist (propranolol) and an adenosine receptor antagonist (8-p
      sulfophenyltheophylline) were assessed on contractile activity and on
      poststimulatory relaxations. 4. Low concentrations of methoctramine (10(-8) m)
      reduced or tended to reduce the EFS-induced contraction, e.g. at 2 Hz by 12%
      while methoctramine at 10(-7) m had no significant effect. In addition, in the
      presence of 4-DAMP (10(-9) m), which tended to inhibit contractions at all
      frequencies (2-20 Hz; -17 to -25%), methoctramine at 10(-8) and 10(-7) m induced
      a further reduction of the contractile responses (-5 to -10%; 2-20 Hz). 5. The
      beta-adrenergic receptor antagonist propranolol (10(-6) m) and the adenosine
      receptor antagonist 8-p-sulfophenyltheophylline (10(-6) m) both increased
      contractile responses by 9-21% (2-10 Hz, long duration; P < 0.05-0.001) as a
      consequence of antagonizing relaxatory stimuli. Neither antagonist affected the
      contractile responses to EFS with the short duration stimulation. Poststimulatory
      relaxations were reduced by 30-60% (P < 0.05) by propranolol and by 40-60% (P <
      0.001) by 8-p-sulfophenyltheophylline, but for 8-p-sulfophenyltheophylline only
      after stimulation with the short duration. 6. In the presence of methoctramine
      (10(-7) m), the 8-p-sulfophenyltheophylline-induced increases of the contractile
      response to long duration EFS were significantly enhanced at 10 Hz (+12 +/- 4%; P
      < 0.05), whereas no such enhancement of the propranolol inhibitory effect
      occurred in the presence of methoctramine. However, poststimulatory beta
      adrenoceptor-evoked relaxations after short duration EFS were increased by about
      35% in the presence of methoctramine, but not those after long duration. 7. Thus,
      muscarinic M(2) receptor activation inhibits adenosine receptor- and beta
      adrenoceptor-evoked relaxations of the rat detrusor muscle. The inhibition occurs
      via a transient postjunctional mechanism that mainly affects responses with a
      short latency.

PMID- 15955032
TI  - A comparison of the effects of the 5HT1A antagonists MM-77 and WAY-100635 on the
      mouse isolated vasa deferentia.
AB  - 1. Experiments were carried out to characterize the possible adrenergic
      properties of the 5-HT(1A) antagonists WAY 100635 and MM-77 using the mouse
      isolated vasa deferentia preparation. 2. When vasa deferentia were preincubated
      for 10 min in the presence of MM-77 (10(-8)-10(-6) m) or WAY100635 (10(-8)-7 x
      10(-7) m), a concentration-dependent inhibition of the contractile response to
      submaximal electrical field stimulation (10 Hz, 50 V, 50 ms) was observed with
      pIC(50) values of 7.05 +/- 0.01 and 6.85 +/- 0.1 respectively. 3. MM-77 (10(-8)
      10(-6) m) antagonized the contractile responses of the vasa deferentia to
      phenylephrine (PE) (10(-6)-10(-3) m) in a concentration-dependent manner. Schild
      plots of these data were linear and yielded a mean rhoA(2) value of 6.81 +/-
      0.084. The mean slope was 1.42 +/- 0.22. 4. WAY100635 (10(-8)-10(-6) m)
      antagonized the contractile responses of the vasa deferentia to PE (10(-6)-10(-3)
      m) in a concentration-dependent manner. Schild plots of these data were linear
      and yielded a mean rhoA(2) value of 7.05 +/- 0.08. The mean slope was 0.97 +/-
      0.1. 5. The results suggest that while WAY100635 acts as a competitive antagonist
      at alpha(1)-adrenoceptors, MM-77 displays non-competitive antagonist
      characteristics at this receptor subtype. 6. These results may have important
      implications for the use of these compounds as 5-HT(1A) receptor antagonists in
      in vivo studies.

PMID- 15955033
TI  - Medication overuse is more than just taking too much.

PMID- 15955034
TI  - Migraine days decline with duration of illness in adolescents with transformed
      migraine.
AB  - The aim of this study was to assess the proportion of subjects with transformed
      migraine (TM) who have 15 or more migraine days per month as a function of
      duration of chronic daily headache (CDH) in an adolescent sample. CDH is a
      syndrome characterized by 15 or more headache days per month. In specialty care,
      TM is the most common type of CDH. Most adults who meet criteria for TM do not
      meet the International Headache Society (IHS) criteria for chronic migraine (CM).
      TM criteria require 15 or more headache days per month (not necessarily
      migraine), with a current or past history of migraine. CM requires 15 or more
      migraine days per month. As TM develops, attack frequency increases and the
      number of migraine features diminishes. If this observation is correct,
      individuals who meet criteria for TM but not CM may be at a later stage in the
      evolution of the disease, compared with those who meet criteria for CM. We
      reviewed charts of 267 adolescents (13-17 years) seen in a headache centre, to
      identify 117 with TM. We divide subjects with TM into those with recent onset
      (</=1 year) vs. longer duration (>1 year) and examined the number of migraine
      days per month and demographic features. We modelled predictors of CM (>15
      migraine days per month) using logistic regression. Of 117 adolescents with TM,
      55 (47%) had recent-onset (<1 year) and 62 (53%) had long-duration TM. Those with
      recent-onset TM were much more likely also to meet criteria for CM (74.5% vs.
      25.8%, P < 0.001). This was verified in the TM with medication overuse subgroup
      (recent onset 66.7%, vs. long duration 37%, P = 0.01) and in the TM without
      medication overuse subgroup (62.2% vs. 19.2%, P = 0.001). Modelling the
      dichotomous outcome of CM (>15 days of migraine/month) in logistic regression, CM
      was predicted by recent onset of CDH, recent onset of migraine (<36 months), and
      younger ages (</=15 years), but not gender or use of migraine preventive drugs or
      medication overuse. Among adolescents with TM, CM is more likely in individuals
      who are young, whose episodic headache began recently, and with CDH of recent
      onset. These findings suggest that early in the process of transformation,
      migraine is more frequent, and that as CDH evolves, fewer typical attacks of IHS
      migraine occur.

PMID- 15955035
TI  - Investigation into sleep disturbance of patients suffering from cluster headache.
AB  - The new discoveries relating to cluster headache (CH) encouraged the study of the
      relationship of the hypothalamus to respiratory physiology and its comorbidity
      with sleep apnoea. The question is whether the apnoeas are more frequent during
      REM sleep and the desaturations could be involved as triggers of the cluster
      attacks. Furthermore, could the connection with the hypothalamus, already proved,
      be responsible for an alteration in the structure of REM sleep and a
      chemoreceptor dysfunction. We set out to analyse when polysomnography
      investigation is necessary in patients with CH. We studied 37 patients suffering
      from episodic CH, 31 (83.8%) men and six (16.2%) women. For the control group, we
      selected 35 individuals, 31 (88.6%) men and four (11.4%) women. There was a
      greater percentage of obstructive sleep apnoea (OSA) in patients with CH (58.3%)
      compared with the control group (14.3%) and with the general population (2-4%).
      In cases of pain during sleep, the majority is deflagrated during the REM phase,
      following a desaturation episode. A stratified analysis of the apnoea/hypnoea
      index relating to body mass index (BMI) and age showed that patients with CH have
      8.4 times more chance of exhibiting OSA than normal individuals (P < 0001). This
      risk increases to 24.38 in patients with a BMI > 25 kg/m(2) and increases to 13.5
      in patients > 40 years old. Surprisingly, the risk decreases sharply in patients
      with a BMI < 25 kg/m(2) and who are < 40 years old. Due to the fact that
      polysomnography is a complex, costly and sometimes difficult examination, we
      suggest, in concordance with the results, that it should be carried out routinely
      in patients with CH that exhibit a BMI of > 25 kg/m(2) and/or in patients who are
      > 40 years of age.

PMID- 15955036
TI  - Prevalence, pattern and predictors of use of complementary and alternative
      medicine (CAM) in migraine patients attending a headache clinic in Italy.
AB  - The use of complementary and alternative medicine (CAM) in migraine is a growing
      phenomenon about which little is known. This study was undertaken to evaluate the
      rates, pattern and presence of predictors of CAM use in a clinical population of
      patients with different migraine subtypes. Four hundred and eighty-one
      migraineurs attending a headache clinic were asked to undergo a physician
      administered structured interview designed to gather information on CAM use. Past
      use of CAM therapies was reported by 31.4% of the patients surveyed, with 17.1%
      having used CAM in the previous year. CAM therapies were perceived as beneficial
      by 39.5% of the patients who had used them. A significantly higher proportion of
      transformed migraine patients reported CAM treatments as ineffective compared
      with patients suffering from episodic migraine (73.1% vs. 50.7%, P < 0.001). The
      most common source of a recommendation of CAM was a friend or relative (52.7%).
      In most cases, migraineurs' recourse to CAM treatments was specifically for their
      headache (89.3%). Approximately 61% of CAM users had not informed their medical
      doctors of their CAM use. The most common reason for deciding to try a CAM
      therapy was that it offered a 'potential improvement of headache' (47.7%). The
      greatest users of CAM treatments were: patients with a diagnosis of transformed
      migraine; those who had consulted a high number of specialists and reported a
      higher lifetime number of conventional medical visits; those with a comorbid
      psychiatric disorder; those with a high income; and those whose headache had been
      either misdiagnosed or not diagnosed at all. Our findings suggest that headache
      clinic migraine patients, in their need of and quest for care, seek and explore
      both conventional and CAM approaches. Physicians should be made aware of this
      patient-driven change in the medical climate in order to prevent misuse of
      healthcare resources and to be better equipped to meet patients' needs.

PMID- 15955037
TI  - MR-spectroscopic imaging during visual stimulation in subgroups of migraine with
      aura.
AB  - Migraine pathophysiology possibly involves deficient mitochondrial energy reserve
      and diminished cortical habituation. Using functional magnetic resonance
      spectroscopic imaging (fMRSI), we studied cortical lactate changes during
      prolonged visual stimulation to search for different pathophysiological
      mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy
      volunteers (HV) and 10 migraine patients were investigated interictally: five
      with visual aura (MA) and five with visual symptoms and at least one of the
      following: paraesthesia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5
      T) (1)H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual
      and non-visual cortex, with the first and fifth measurements in darkness and the
      second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased
      only during stimulation, only in visual cortex; in MA resting lactate was high in
      visual cortex, without further increase during stimulation. This is compatible
      with an abnormal metabolic strain during stimulation in MAplus, possibly due to
      dishabituation, and a predominant mitochondrial dysfunction in MA.

PMID- 15955038
TI  - Psychiatric comorbidity in the evolution from migraine to medication overuse
      headache.
AB  - We set out to study the role of psychiatric comorbidity in the evolution of
      migraine to medication overuse headache (MOH) by a comparative study of 41
      migraineurs (MIG) and 41 patients suffering from MOH deriving from migraine.
      There was an excess risk of suffering from mood disorders [odds ratio (OR) = 4.5,
      95% confidence interval (CI) 1.5, 13.5], anxiety (OR = 5, 95% CI 1.2, 10.7) and
      disorders associated with the use of psychoactive substances other than
      analgesics (OR = 7.6, 95% CI 2.2, 26.0) in MOH compared with MIG. Retrospective
      study of the order of occurrence of disorders showed that in the MOH group,
      psychiatric disorders occurred significantly more often before the transformation
      from migraine into MOH than after. There was no crossed-family transmission
      between MOH and psychiatric disorders, except for substance-related disorders.
      MOH patients have a greater risk of suffering from anxiety and depression, and
      these disorders may be a risk factor for the evolution of migraine into MOH.
      Moreover, MOH patients have a greater risk of suffering from substance-related
      disorders than MIG sufferers. This could be due to the fact that MOH is part of
      the spectrum of addictive disorders.

PMID- 15955039
TI  - When should an epidural blood patch be performed in postlumbar puncture headache?
      A theoretical approach based on a cohort of 79 patients.
AB  - The aim of the present study was to decide on which day in the course of
      postlumbar puncture headache (PPH) an epidural blood patch (EBP) should be
      performed to minimize suffering. A cohort of 79 patients (64 female, 15 male) was
      followed prospectively for 14 days and the consequences of performing an EBP on
      different days were studied. If no EBP was performed, the patients would
      accumulate 141 days with PPH5 (bedridden most of the day), 216 days with PPH4-5
      (bedridden more than half the day), and 293 days with PPH3-5 (bedridden half the
      day or more). If these patients were patched on day 2, 3 or 4 after an initial
      observation of the PPH grade on day 1, the expected suffering was substantially
      reduced, and the more the earlier in the course the EBP was performed. If the
      strategy was to treat only patients with PPH5 with an expected 90% success rate,
      the reduction compared with no treatment was 50% if treated on day 2, 37% if
      treated on day 3, and 29% if treated on day 4. The corresponding figures for
      treating patients with PPH4-5 was a 51, 44 and 29% reduction, and for PPH3-5 the
      reduction was 62, 49 and 35%, respectively. Irrespective of strategy, the
      expected reduction of suffering in the cohort was greatest when the EBP was
      performed early in the course of PPH. It is suggested that the decision to
      perform an EBP should be made at an early stage and offered to patients who have
      to lie in bed for more than half a day despite conservative treatment.

PMID- 15955040
TI  - The impact of migraine on epilepsy: a prospective prognosis study.
AB  - The effect of migraine on the prognosis of epilepsy has not been reported. The
      aim of this prospective 5-10-year follow-up study was to examine some outcome
      measures and the cumulative probability of being seizure-free in epilepsy
      patients with migraine, and to compare their results with those of epilepsy
      patients without migraine. Fifty-nine patients (40 women; mean age 25 years) were
      diagnosed with both epilepsy and migraine (EM group). The control group consisted
      of 56 patients with epilepsy but without migraine (E group). Both groups were
      recruited and followed up over similar periods. We compared the outcome variables
      in the EM group with those in the E group. Kaplan-Meier methods were used to
      assess the seizure-free curves. The EM group had a significantly lower cumulative
      probability of being seizure-free over 10 years compared with the E group. The
      other epilepsy outcome measures at follow-up differed significantly between the
      groups, with the EM group having a longer duration of epilepsy, a lower early
      treatment response, and a higher incidence of intractable epilepsy and achieving
      remission with polytherapy, and more seizure control and medication problems for
      at least the last 2 years of follow-up. Comorbid migraine had a negative effect
      on the prognosis of epilepsy.

PMID- 15955041
TI  - Platelet activation and platelet-leucocyte interaction in patients with migraine.
      Subtype differences and influence of triptans.
AB  - As migraine is the result of an inflammatory mechanism with serotonergic
      signalling, leucocyte function, platelet function and intercellular communication
      between those cells is likely to be connected to the final pathway of the
      disease. We examined P-selectin expression on platelets (platelet activation) and
      leucocyte-platelet aggregate formation in 72 migraine patients during their
      attack-free interval and controls using a flow cytometric assay. Patients
      suffering from migraine without aura had a significantly increased platelet
      activation and leucocyte-platelet aggregation compared with the control group,
      unlike the migraine patients with aura. Patients who had taken a triptan within 3
      days prior to the investigation showed platelet activation values similar to the
      control group. The variations in platelet activation patterns of migraine
      subgroups could indicate different pathomechanisms. Even outside an attack,
      migraine patients, particularly those without aura, show an increased level of
      platelet activation which seems to be down-regulated by triptans. This mechanism
      may account for the triptan-induced increases in headache frequency. The
      involvement of proinflammatory platelet-leucocyte cross-talk suggests a possible
      therapeutic strategy using anti-inflammatory drugs.

PMID- 15955042
TI  - Migraine headache in patients with Sydenham's chorea.
AB  - We compared the frequency of migraine among Sydenham's chorea (SC) patients,
      rheumatic fever (RF) patients without neurological symptoms and matched controls.
      Migraine was more frequent in SC patients (12/55, 21.8%) than in controls (9/110,
      8.1%) and as common as in the RF group (10/55, 18.2%). Our data are in agreement
      with previous studies reporting higher frequency of migraine in other basal
      ganglia disorders, such as essential tremor and Tourette's syndrome.

PMID- 15955043
TI  - Medication overuse headache (MOH) is a biobehavioural disorder.

PMID- 15955044
TI  - Paroxysmal hemicrania-tic syndrome responsive to acetazolamide.

PMID- 15955045
TI  - Isolated sudden-onset hearing loss as a manifestation of recurrent CSF leak.

PMID- 15955046
TI  - Vertebral artery vascular loop in SUNCT and concomitant trigeminal neuralgia.
      Case report.

PMID- 15955048
TI  - Meningeal enhancement and low CSF pressure headache. An MRI study.

PMID- 15955050
TI  - CTTH patients under pressure.

PMID- 15955052
TI  - Methods to monitor the quaternary structure of G protein-coupled receptors.
AB  - A wide range of approaches has been applied to examine the quaternary structure
      of G protein-coupled receptors, the basis of such protein-protein interactions
      and how such interactions might modulate the pharmacology and function of these
      receptors. These include co-immunoprecipitation, various adaptations of resonance
      energy transfer techniques, functional complementation studies and the analysis
      of ligand-binding data. Each of the available techniques has limitations that
      restrict interpretation of the data. However, taken together, they provide a
      coherent body of evidence indicating that many, if not all, G protein-coupled
      receptors exist and function as dimer/oligomers. Herein we assess the widely
      applied techniques and discuss the relative benefits and limitations of these
      approaches.

PMID- 15955053
TI  - The study of G-protein coupled receptor oligomerization with computational
      modeling and bioinformatics.
AB  - To achieve a structural context for the analysis of G-protein coupled receptor
      (GPCR) oligomers, molecular modeling must be used to predict the corresponding
      interaction interfaces. The task is complicated by the paucity of detailed
      structural data at atomic resolution, and the large number of possible modes in
      which the bundles of seven transmembrane (TM) segments of the interacting GPCR
      monomers can be packed together into dimers and/or higher-order oligomers.
      Approaches and tools offered by bioinformatics can be used to reduce the
      complexity of this task and, combined with computational modeling, can serve to
      yield testable predictions for the structural properties of oligomers. Most of
      the bioinformatics methods take advantage of the evolutionary relation that
      exists among GPCRs, as expressed in their sequences and measurable in the common
      elements of their structural and functional features. These common elements are
      responsible for the presence of detectable patterns of motifs and correlated
      mutations evident from the alignment of the sequences of these complex biological
      systems. The decoding of these patterns in terms of structural and functional
      determinants can provide indications about the most likely interfaces of
      dimerization/oligomerization of GPCRs. We review here the main approaches from
      bioinformatics, enhanced by computational molecular modeling, that have been used
      to predict likely interfaces of dimerization/oligomerization of GPCRs, and
      compare results from their application to rhodopsin-like GPCRs. A compilation of
      the most frequently predicted GPCR oligomerization interfaces points to specific
      regions of TMs 4-6.

PMID- 15955054
TI  - The impact of G-protein-coupled receptor hetero-oligomerization on function and
      pharmacology.
AB  - Although highly controversial just a few years ago, the idea that G-protein
      coupled receptors (GPCRs) may undergo homo-oligomerization or hetero
      oligomerization has recently gained considerable attention. The recognition that
      GPCRs may exhibit either dimeric or oligomeric structures is based on a number of
      different biochemical and biophysical approaches. Although much effort has been
      spent to demonstrate the mechanism(s) by which GPCRs interact with each other,
      the physiological relevance of this phenomenon remains elusive. An additional
      source of uncertainty stems from the realization that homo-oligomerization and
      hetero-oligomerization of GPCRs may affect receptor binding and activity in
      different ways, depending on the type of interacting receptors. In this brief
      review, the functional and pharmacological effects of the hetero-oligomerization
      of GPCR on binding and cell signaling are critically analyzed.

PMID- 15955055
TI  - Allosteric functioning of dimeric class C G-protein-coupled receptors.
AB  - Whereas most membrane receptors are oligomeric entities, G-protein-coupled
      receptors have long been thought to function as monomers. Within the last 15
      years, accumulating data have indicated that G-protein-coupled receptors can form
      dimers or even higher ordered oligomers, but the general functional significance
      of this phenomena is not yet clear. Among the large G-protein-coupled receptor
      family, class C receptors represent a well-recognized example of constitutive
      dimers, both subunits being linked, in most cases, by a disulfide bridge. In this
      review article, we show that class C G-protein-coupled receptors are multidomain
      proteins and highlight the importance of their dimerization for activation. We
      illustrate several consequences of this in terms of specific functional
      properties and drug development.

PMID- 15955056
TI  - Pharmacology of vascular endothelium. Delivered on 27 June 2004 at the 29th FEBS
      Congress in Warsaw.
AB  - Sir John Vane named vascular endothelium 'the maestro of blood circulation'.
      Recently, 'the maestro' has become a target for pharmacotherapy of
      atherothrombotic and diabetic vasculopathies with well known cardio-vascular
      drugs belonging to the families of Angiotensin Converting Enzyme inhibitors, HMG
      CoA reductase inhibitors or beta1-Adrenoceptor antagonists. These drugs became
      upgraded to a position of the pleiotropic endothelial drugs. It is not a simple
      verbal change in the nomenclature. It means that these drugs apart from their
      well defined mechanisms of action, as indicated in their regular names, in
      addition they act in an unknown mechanism at the level of vascular endothelium
      preventing angina, myocardial infarction and stroke. Many biochemical events take
      place in endothelial cells. I chose for a closer inspection the nitric
      oxide/prostacyclin defensive system to explain the endothelial pleiotropism of
      the drugs in question. I tried to examine the validity of this conception
      according to the general rule: in vitro cognitio sed in vivo veritas.

PMID- 15955057
TI  - Substrate positioning by His92 is important in catalysis by purple acid
      phosphatase.
AB  - Proteolysis of single polypeptide mammalian purple acid phosphatases (PAPs)
      results in the loss of an interaction between the loop residue Asp146 and the
      active site residues Asn91 and/or His92. While Asn91 is a ligand to the divalent
      metal of the mixed-valent di-iron center, the role of His92 in the catalytic
      mechanism is unknown. Site-directed mutagenesis of His92 was performed to examine
      the role of this residue in single polypeptide PAP. Conversion of His92 into Ala,
      which eliminates polar interactions of this residue with the active site,
      resulted in a 10-fold decrease in catalytic activity at the optimal pH.
      Conversely, conversion of this residue into Asn, which cannot function as either
      a proton donor or acceptor, but can provide hydrogen-bonding interactions,
      resulted in a three-fold increase in activity at the optimal pH. Both mutant
      enzymes had more acidic pH optima, with pK(es,1) values consistent with the
      involvement of an iron(III) hydroxide unit or a hydroxide in the second
      coordination sphere in catalysis. These results, together with EPR data, support
      a role of His92 in positioning either the nucleophile or the substrate, rather
      than directly in acid or base catalysis. The existence of an extensive hydrogen
      bonding network that could fine-tune the position of His92 is consistent with
      this proposal.

PMID- 15955058
TI  - Calcium modulates endopeptidase 24.15 (EC 3.4.24.15) membrane association,
      secondary structure and substrate specificity.
AB  - The metalloendopeptidase 24.15 (EP24.15) is ubiquitously present in the
      extracellular environment as a secreted protein. Outside the cell, this enzyme
      degrades several neuropeptides containing from 5 to 17 amino acids (e.g.
      gonadotropin releasing hormone, bradykinin, opioids and neurotensin). The
      constitutive secretion of EP24.15 from glioma C6 cells was demonstrated to be
      stimulated linearly by reduced concentrations of extracellular calcium. In the
      present report we demonstrate that extracellular calcium concentration has no
      effect on the total amount of the extracellular (cell associated + medium)
      enzyme. Indeed, immuno-cytochemical analyses by confocal and electron microscopy
      suggested that the absence of calcium favors the enzyme shedding from the plasma
      membrane into the medium. Two putative calcium-binding sites on EP24.15 (D93 and
      D159) were altered by site-directed mutagenesis to investigate their possible
      contribution to binding of the enzyme at the cell surface. These mutated
      recombinant proteins behave similarly to the wild-type enzyme regarding enzymatic
      activity, secondary structure, calcium sensitivity and immunoreactivity. However,
      immunocytochemical analyses by confocal microscopy consistently show a reduced
      ability of the D93A mutant to associate with the plasma membrane of glioma C6
      cells when compared with the wild-type enzyme. These data and the model of the
      enzyme's structure as determined by X-ray diffraction suggest that D93 is located
      at the enzyme surface and is consistent with membrane association of EP24.15.
      Moreover, calcium was also observed to induce a major change in the EP24.15
      cleavage site on distinctive fluorogenic substrates. These data suggest that
      calcium may be an important modulator of ep24.15 cell function.

PMID- 15955059
TI  - Inhibition of the D-alanine:D-alanyl carrier protein ligase from Bacillus
      subtilis increases the bacterium's susceptibility to antibiotics that target the
      cell wall.
AB  - The surface charge as well as the electrochemical properties and ligand binding
      abilities of the Gram-positive cell wall is controlled by the D-alanylation of
      the lipoteichoic acid. The incorporation of D-Ala into lipoteichoic acid requires
      the D-alanine:D-alanyl carrier protein ligase (DltA) and the carrier protein
      (DltC). We have heterologously expressed, purified, and assayed the substrate
      selectivity of the recombinant proteins DltA with its substrate DltC. We found
      that apo-DltC is recognized by both endogenous 4'-phosphopantetheinyl
      transferases AcpS and Sfp. After the biochemical characterization of DltA and
      DltC, we designed an inhibitor (D-alanylacyl-sulfamoyl-adenosine), which is able
      to block the D-Ala adenylation by DltA at a K(i) value of 232 nM vitro. We also
      performed in vivo studies and determined a significant inhibition of growth for
      different Bacillus subtilis strains when the inhibitor is used in combination
      with vancomycin.

PMID- 15955060
TI  - Diverging regulation of pyruvate dehydrogenase kinase isoform gene expression in
      cultured human muscle cells.
AB  - The pyruvate dehydrogenase complex occupies a central and strategic position in
      muscle intermediary metabolism and is primarily regulated by
      phosphorylation/dephosphorylation. The identification of multiple isoforms of
      pyruvate dehydrogenase kinase (PDK1-4) and pyruvate dehydrogenase phosphatase
      (PDP1-2) has raised intriguing new possibilities for chronic pyruvate
      dehydrogenase complex control. Experiments to date suggest that PDK4 is the major
      isoenzyme responsible for changes in pyruvate dehydrogenase complex activity in
      response to various different metabolic conditions. Using a cultured human
      skeletal muscle cell model system, we found that expression of both PDK2 and PDK4
      mRNA is upregulated in response to glucose deprivation and fatty acid
      supplementation, the effects of which are reversed by insulin treatment. In
      addition, insulin directly downregulates PDK2 and PDK4 mRNA transcript abundance
      via a phosphatidylinositol 3-kinase-dependent pathway, which may involve glycogen
      synthase kinase-3 but does not utilize the mammalian target of rapamycin or
      mitogen-activated protein kinase signalling pathways. In order to further
      elucidate the regulation of PDK, the role of the peroxisome proliferators
      activated receptors (PPAR) was investigated using highly potent subtype selective
      agonists. PPARalpha and PPARdelta agonists were found to specifically upregulate
      PDK4 mRNA expression, whereas PPARgamma activation selectively decreased PDK2
      mRNA transcript abundance. PDP1 mRNA expression was unaffected by all conditions
      analysed. These results suggest that in human muscle, hormonal and nutritional
      conditions may control PDK2 and PDK4 mRNA expression via a common signalling
      mechanism. In addition, PPARs appear to independently regulate specific PDK
      isoform transcipt levels, which are likely to impart important metabolic
      mediation of fuel utilization by the muscle.

PMID- 15955061
TI  - Unusual venom phospholipases A2 of two primitive tree vipers Trimeresurus
      puniceus and Trimeresurus borneensis.
AB  - To explore the venom diversity of Asian pit vipers, we investigated the structure
      and function of venom phospholipase A2 (PLA2) derived from two primitive tree
      vipers Trimeresurus puniceus and Trimeresurus borneensis. We purified six novel
      PLA2s from T. puniceus venom and another three from T. borneensis venom. All
      cDNAs encoding these PLA2s except one were cloned, and the molecular masses and N
      terminal sequences of the purified enzymes closely matched those predicted from
      the cDNA. Three contain K49 and lack a disulfide bond at C61-C91, in contrast
      with the D49-containing PLA2s in both venom species. They are less thermally
      stable than other K49-PLA2s which contain seven disulfide bonds, as indicated by
      a decrease of 8.8 degrees C in the melting temperature measured by CD
      spectroscopy. The M110D mutation in one of the K49-PLA2s apparently reduced its
      edematous potency. A phylogenetic tree based on the amino-acid sequences of 17
      K49-PLA2s from Asian pit viper venoms illustrates close relationships among the
      Trimeresurus species and intergeneric segregations. Basic D49-PLA2s with a unique
      Gly6 substitution were also purified from both venoms. They showed edema-inducing
      and anticoagulating activities. It is notable that acidic PLA2s from both venoms
      inhibited blood coagulation rather than platelet aggregation, and this inhibition
      was only partially dependent on enzyme activity. These results contribute to our
      understanding of the evolution of Trimeresurus pit vipers and the structure
      function relationships between various subtypes of crotalid venom PLA2.

PMID- 15955062
TI  - Slc12a2 is a direct target of two closely related homeobox proteins, Six1 and
      Six4.
AB  - Six genes are homologs of Drosophila sine oculis and encode transcription factors
      that are characterized by a conserved Six domain and homeodomain. Of the six
      family members (Six1-Six6) in mice, Six1 and Six4 show similar expression
      patterns during embryogenesis. Six1-/- mice show defective formation of various
      organs such as inner ear, nose, skeletal muscle, kidney and thymus, whereas Six4
      /- mice show little anomaly in organogenesis. To understand the molecular basis
      for the differential function of Six1 and Six4 in vivo, we screened target genes
      of Six1 and Six4 and found that Six1 and Six4 differentially regulated a set of
      target genes. Gel-retardation assays indicated that the promoter region of one of
      the targets, sodium-potassium-chloride cotransporter 1 (Slc12a2), contains
      multiple Six1-binding sites and one common binding site of Six1 and Six4,
      suggesting that the DNA-binding specificity of Six1 is distinct from that of
      Six4. This underlies the differential regulation of common target genes by Six1
      and Six4. Furthermore, in situ hybridization demonstrated that the expression of
      Slc12a2 was reduced in the developing dorsal root ganglia of Six1-/-/Six4-/-
      mice, suggesting that Six1 and Six4 regulate Slc12a2 in vivo.

PMID- 15955063
TI  - Interaction of human stefin B in the prefibrillar oligomeric form with membranes.
      Correlation with cellular toxicity.
AB  - Protein aggregation is central to most neurodegenerative diseases, as shown by
      familial case studies and by animal models. A modified 'amyloid cascade'
      hypothesis for Alzheimer's disease states that prefibrillar oligomers, also
      called amyloid-beta-derived diffusible ligands or globular oligomers, are the
      responsible toxic agent. It has been proposed that these oligomeric species, as
      shown for amyloid-beta, beta2-microglobulin or prion fragments, exert toxicity by
      forming pores in membranes, initiating a cascade of detrimental events for the
      cell. Interaction of granular aggregates and globular oligomers of an
      amyloidogenic protein, human stefin B, with model lipid membranes and monolayers
      was studied. Prefibrillar oligomers/aggregates of stefin B are shown to cause
      concentration-dependent membrane leaking, in contrast to the homologous stefin A.
      Prefibrillar oligomers/aggregates of stefin B also increase the surface pressure
      at an air-water interface, i.e. they have amphipathic character and are surface
      seeking. In addition, they show stronger interaction with 1,2-dioleoyl-sn-glycero
      3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)]
      monolayers than native stefin A or nonaggregated stefin B. Prefibrillar
      aggregates interact predominantly with acidic phospholipids, such as
      dioleoylphosphatidylglycerol or dipalmitoylphosphatidylserine, as shown by
      calcein release experiments and surface plasmon resonance. The same preparations
      are toxic to neuroblastoma cells, as determined by the 3-(4,5-dimethylthiazol-2
      yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, again in
      contrast to the homologue stefin A, which does not aggregate under any of the
      conditions studied. This study is aimed to contribute to the general model of
      cellular toxicity induced by prefibrillar oligomers of amyloidogenic proteins,
      not necessarily involved in pathology.

PMID- 15955064
TI  - Two short protein domains are responsible for the nuclear localization of the
      mouse spermine oxidase mu isoform.
AB  - In mouse, at least two catalytically active splice variants (mSMOalpha and
      mSMOmicro) of the flavin-containing spermine oxidase enzyme are present. We have
      demonstrated previously that the cytosolic mSMOalpha is the major isoform, while
      the mSMOmicro enzyme is present in both nuclear and cytoplasmic compartments and
      has an extra protein domain corresponding to the additional exon VIa. By amino
      acid sequence comparison and molecular modeling of mSMO proteins, we identified a
      second domain that is necessary for nuclear localization of the mSMOmicro splice
      variant. A deletion mutant enzyme of this region was constructed to demonstrate
      its role in protein nuclear targeting by means of transient expression in the
      murine neuroblastoma cell line, N18TG2.

PMID- 15955065
TI  - Evolutionary and experimental analyses of inorganic phosphate transporter PiT
      family reveals two related signature sequences harboring highly conserved
      aspartic acids critical for sodium-dependent phosphate transport function of
      human PiT2.
AB  - The mammalian members of the inorganic phosphate (P(i)) transporter (PiT) family,
      the type III sodium-dependent phosphate (NaP(i)) transporters PiT1 and PiT2, have
      been assigned housekeeping P(i) transport functions and are suggested to be
      involved in chondroblastic and osteoblastic mineralization and ectopic
      calcification. The PiT family members are conserved throughout all kingdoms and
      use either sodium (Na+) or proton (H+) gradients to transport P(i). Sequence logo
      analyses revealed that independent of their cation dependency these proteins
      harbor conserved signature sequences in their N- and C-terminal ends with the
      common core consensus sequence GANDVANA. With the exception of 10 proteins from
      extremophiles all 109 proteins analyzed carry an aspartic acid in one or both of
      the signature sequences. We changed either of the highly conserved aspartates,
      Asp28 and Asp506, in the N- and C-terminal signature sequences, respectively, of
      human PiT2 to asparagine and analyzed P(i) uptake function in Xenopus laevis
      oocytes. Both mutant proteins were expressed at the cell surface of the oocytes
      but exhibited knocked out NaP(i) transport function. Human PiT2 is also a
      retroviral receptor and we have previously shown that this function can be
      exploited as a control for proper processing and folding of mutant proteins. Both
      mutant transporters displayed wild-type receptor functions implying that their
      overall architecture is undisturbed. Thus the presence of an aspartic acid in
      either of the PiT family signature sequences is critical for the Na+-dependent
      P(i) transport function of human PiT2. The conservation of the aspartates among
      proteins using either Na+- or H+-gradients for P(i) transport suggests that they
      are involved in H+-dependent P(i) transport as well. Current results favor a
      membrane topology model in which the N- and C-terminal PiT family signature
      sequences are positioned in intra- and extracellular loops, respectively,
      suggesting that they are involved in related functions on either side of the
      membrane. The present data are in agreement with a possible role of the signature
      sequences in translocation of cations.

PMID- 15955066
TI  - A DmpA-homologous protein from Pseudomonas sp. is a dipeptidase specific for beta
      alanyl dipeptides.
AB  - We have determined the nucleotide sequence of a DNA fragment covering the
      flanking region of the R-stereoselective amidase gene, ramA, from the Pseudomonas
      sp. MCI3434 genome and found an additional gene, bapA, coding for a protein
      showing sequence similarity to DmpA aminopeptidase from Ochrobactrum anthropi
      LMG7991 (43% identity). The DmpA (called L-aminopeptidase D-Ala-esterase/amidase)
      hydrolyzes alanine-p-nitroanilide, alaninamide, and alanine methylester with a
      preference for the D-configuration of the alanine, whereas the enzyme acts as an
      L-stereoselective aminopeptidase on a tripeptide Ala-(Gly)2, indicating a reverse
      stereoselectivity [Fanuel L, Goffin C, Cheggour A, Devreese B, Van Driessche G,
      Joris B, Van Beeumen J & Frere J-M (1999) Biochem J341, 147-155]. A recombinant
      BapA exhibiting hydrolytic activity toward D-alanine-p-nitroanilide was purified
      from the cell-free extract of an Escherichia coli transformant overexpressing the
      bapA gene and characterized. The purified enzyme contained two polypeptides
      corresponding to residues 1-238 (alpha-peptide) and 239-366 (beta-peptide) of the
      precursor as observed for DmpA. On gel-filtration chromatography, BapA in the
      native form appeared to be a tetramer. It had maximal activity at 60 degrees C
      and pH 9.0-10.0, and was inactivated in the presence of p-chloromercuribenzoate,
      N-ethylmaleimide, dithiothreitol, Zn2+, Ag+, Cd2+ or Hg2+. The enzyme hydrolyzed
      D-alanine-p-nitroanilide more efficiently than L-alanine-p-nitroanilide the same
      as DmpA. Furthermore, BapA was found to hydrolyze peptide bonds of beta-alanyl
      dipeptides including beta-Ala-L-Ala, beta-Ala-Gly, beta-Ala-L-His (carnosine),
      beta-Ala-L-Leu, and (beta-Ala)2 with high efficiency compared to D-alanine-p
      nitroanilide. Beta-alaninamide was also efficiently hydrolyzed, but the enzyme
      did not act on the peptides containing proteinogenic amino acids or their D
      counterparts for N-terminal residues. Based on its unique substrate specificity,
      the enzyme should not be called L-aminopeptidase D-Ala-esterase/amidase but beta
      Ala-Xaa dipeptidase.

PMID- 15955067
TI  - Adenylyl cyclase Rv0386 from Mycobacterium tuberculosis H37Rv uses a novel mode
      for substrate selection.
AB  - Class III adenylyl cyclases usually possess six highly conserved catalytic
      residues. Deviations in these canonical amino acids are observed in several
      putative adenylyl cyclase genes as apparent in several bacterial genomes. This
      suggests that a variety of catalytic mechanisms may actually exist. The gene
      Rv0386 from Mycobacterium tuberculosis codes for an adenylyl cyclase catalytic
      domain fused to an AAA-ATPase and a helix-turn-helix DNA-binding domain. In
      Rv0386, the standard substrate, adenine-defining lysine-aspartate couple is
      replaced by glutamine-asparagine. The recombinant adenylyl cyclase domain was
      active with a V(max) of 8 nmol cAMP.mg(-1).min(-1). Unusual for adenylyl
      cyclases, Rv0386 displayed 20% guanylyl cyclase side-activity with GTP as a
      substrate. Mutation of the glutamine-asparagine pair either to alanine residues
      or to the canonical lysine-aspartate consensus abolished activity. This argues
      for a novel mechanism of substrate selection which depends on two non-canonical
      residues. Data from individual and coordinated point mutations suggest a model
      for purine definition based on an amide switch related to that previously
      identified in cyclic nucleotide phosphodiesterases.

PMID- 15955068
TI  - 7-Ketocholesterol-induced apoptosis. Involvement of several pro-apoptotic but
      also anti-apoptotic calcium-dependent transduction pathways.
AB  - Oxysterols, and particularly 7-ketocholesterol, appear to be strongly involved in
      the physiopathology of atherosclerosis. These molecules are suspected to be
      cytotoxic to the cells of the vascular wall and monocytes/macrophages,
      particularly by inducing apoptosis. Previous studies have demonstrated that 7
      ketocholesterol-induced apoptosis is triggered by a sustained increase of
      cytosolic-free Ca2+, which elicits the mitochondrial pathway of apoptosis by
      activation of the calcium-dependent phosphatase calcineurin, leading to
      dephosphorylation of the 'BH3 only' protein BAD. However, thorough study of the
      results suggests that other pathways are implicated in 7-ketocholesterol-induced
      cytotoxicity. In this study, we demonstrate the involvement of two other calcium
      dependent pathways during 7-ketocholesterol-induced apoptosis. The activation of
      the MEK-->ERK pathway by the calcium-dependent tyrosine kinase PYK 2, a survival
      pathway which delays apoptosis as shown by the use of the MEK inhibitor U0126,
      and a pathway involving another pro-apoptotic BH3 only protein, Bim. Indeed, 7
      ketocholesterol treatment of human monocytic THP-1 cells induces the release of
      Bim-LC8 from the microtubule-associated dynein motor complex, and its association
      with Bcl-2. Therefore, it appears that 7-ketocholesterol-induced apoptosis is a
      complex phenomenon resulting from calcium-dependent activation of several pro
      apoptotic pathways and also one survival pathway.

PMID- 15955069
TI  - Mechanism of binding of serum response factor to serum response element.
AB  - Serum response factor (SRF) is a MADS transcription factor that binds to the CArG
      box sequence of the serum response element (SRE). Through its binding to CArG
      sequences, SRF activates several muscle-specific genes as well as genes that
      respond to mitogens. The thermodynamic parameters of the interaction of core-SRF
      (the 124-245 fragment of serum response factor) with specific oligonucleotides
      from c-fos and desmin promoters, were determined by spectroscopy. The rotational
      correlation time of core-SRF labeled with bis-ANS showed that the protein is
      monomeric at low concentration (10(-7) m). The titration curves for the
      fluorescence anisotropy of fluorescein-labeled oligonucleotide revealed that
      under equilibrium conditions, the core-SRF monomers were bound sequentially to
      SRE at very low concentration (10(-9) m). Curve-fitting data showed also major
      differences between the wild-type sequence and the oligonucleotide sequences
      mutated within the CArG box. The fluorescence of the core-SRF tyrosines was
      quenched by the SRE oligonucleotide. This quenching indicated that under
      stoichiometric conditions, core-SRF was bound as a dimer to the wild-type
      oligonucleotide, and as a monomer or a tetramer to the mutant oligonucleotides.
      Far-UV CD spectra indicated that the flexibility of core-SRF changed profoundly
      upon its binding to its specific target SRE. Lastly, the rotational correlation
      time of fluorescein-labeled SRE revealed that formation of the specific complex
      was accompanied by a change in the SRE internal dynamics. These results indicated
      that the flexibility of the two partners is crucial for the DNA-protein
      interaction.

PMID- 15955070
TI  - Regulation of arginase II by interferon regulatory factor 3 and the involvement
      of polyamines in the antiviral response.
AB  - The innate antiviral response requires the induction of genes and proteins with
      activities that limit virus replication. Among these, the well-characterized
      interferon beta (IFNB) gene is regulated through the cooperation of AP-1, NF
      kappaB and interferon regulatory factor 3 (IRF-3) transcription factors. Using a
      constitutively active form of IRF-3, IRF-3 5D, we showed previously that IRF-3
      also regulates an IFN-independent antiviral response through the direct induction
      of IFN-stimulated genes. In this study, we report that the arginase II gene
      (ArgII) as well as ArgII protein concentrations and enzymatic activity are
      induced in IRF-3 5D-expressing and Sendai virus-infected Jurkat cells in an IFN
      independent manner. ArgII is a critical enzyme in the polyamine-biosynthetic
      pathway. Of the natural polyamines, spermine possesses antiviral activity and
      mediates apoptosis at physiological concentrations. Measurement of intracellular
      polyamine content revealed that expression of IRF-3 5D induces polyamine
      production, but that Sendai virus and vesicular stomatitis virus infections do
      not. These results show for the first time that the ArgII gene is an early IRF-3
      regulated gene, which participates in the IFN-independent antiviral response
      through polyamine production and induction of apoptosis.

PMID- 15955071
TI  - An alcohol acyl transferase from apple (cv. Royal Gala), MpAAT1, produces esters
      involved in apple fruit flavor.
AB  - Apple flavor is characterized by combinations of ester compounds, which increase
      markedly during fruit ripening. The final step in ester biosynthesis is catalyzed
      by alcohol acyl transferases (AATs) that use coenzyme A (CoA) donors together
      with alcohol acceptors as substrates. The gene MpAAT1, which produces a predicted
      protein containing features of other plant acyl transferases, was isolated from
      Malus pumila (cv. Royal Gala). The MpAAT1 gene is expressed in leaves, flowers
      and fruit of apple. The recombinant enzyme can utilize a range of alcohol
      substrates from short to medium straight chain (C3-C10), branched chain, aromatic
      and terpene alcohols. The enzyme can also utilize a range of short to medium
      chain CoAs. The binding of the alcohol substrate is rate limiting compared with
      the binding of the CoA substrate. Among different alcohol substrates there is
      more variation in turnover compared with K(m) values. MpAAT1 is capable of
      producing many esters found in Royal Gala fruit, including hexyl esters, butyl
      acetate and 2-methylbutyl acetate. Of these, MpAAT1 prefers to produce the hexyl
      esters of C3, C6 and C8 CoAs. For the acetate esters, however, MpAAT1 preference
      depends upon substrate concentration. At low concentrations of alcohol substrate
      the enzyme prefers utilizing the 2-methylbutanol over hexanol and butanol, while
      at high concentrations of substrate hexanol can be used at a greater rate than 2
      methylbutanol and butanol. Such kinetic characteristics of AATs may therefore be
      another important factor in understanding how the distinct flavor profiles of
      different fruit are produced during ripening.

PMID- 15955072
TI  - Calcium-induced contraction of sarcomeres changes the regulation of mitochondrial
      respiration in permeabilized cardiac cells.
AB  - The relationships between cardiac cell structure and the regulation of
      mitochondrial respiration were studied by applying fluorescent confocal
      microscopy and analysing the kinetics of mitochondrial ADP-stimulated
      respiration, during calcium-induced contraction in permeabilized cardiomyocytes
      and myocardial fibers, and in their 'ghost' preparations (after selective myosin
      extraction). Up to 3 microm free calcium, in the presence of ATP, induced strong
      contraction of permeabilized cardiomyocytes with intact sarcomeres, accompanied
      by alterations in mitochondrial arrangement and a significant decrease in the
      apparent K(m) for exogenous ADP and ATP in the kinetics of mitochondrial
      respiration. The V(max) of respiration showed a moderate (50%) increase, with an
      optimum at 0.4 microm free calcium and a decrease at higher calcium
      concentrations. At high free-calcium concentrations, the direct flux of ADP from
      ATPases to mitochondria was diminished compared to that at low calcium levels.
      All of these effects were unrelated either to mitochondrial calcium overload or
      to mitochondrial permeability transition and were not observed in 'ghost'
      preparations after the selective extraction of myosin. Our results suggest that
      the structural changes transmitted from contractile apparatus to mitochondria
      modify localized restrictions of the diffusion of adenine nucleotides and thus
      may actively participate in the regulation of mitochondrial function, in addition
      to the metabolic signalling via the creatine kinase system.

PMID- 15955073
TI  - Translational incorporation of L-3,4-dihydroxyphenylalanine into proteins.
AB  - An Escherichia coli cell-free transcription/translation system was used to
      explore the high-level incorporation of L-3,4-dihydroxyphenylalanine (DOPA) into
      proteins by replacing tyrosine with DOPA in the reaction mixtures. ESI-MS showed
      specific incorporation of DOPA in place of tyrosine. More than 90% DOPA
      incorporation at each tyrosine site was achieved, allowing the recording of clean
      15N-HSQC NMR spectra. A redox-staining method specific for DOPA was shown to
      provide a sensitive and generally applicable method for assessing the cell-free
      production of proteins. Of four proteins produced in soluble form in the presence
      of tyrosine, two resulted in insoluble aggregates in the presence of high levels
      of DOPA. DOPA has been found in human proteins, often in association with various
      disease states that implicate protein aggregation and/or misfolding. Our results
      suggest that misfolded and aggregated proteins may result, in principle, from
      ribosome-mediated misincorporation of intracellular DOPA accumulated due to
      oxidative stress. High-yield cell-free protein expression systems are uniquely
      suited to obtain rapid information on solubility and aggregation of nascent
      polypeptide chains.

PMID- 15955074
TI  - Relationship between the structure of guanidines and N-hydroxyguanidines, their
      binding to inducible nitric oxide synthase (iNOS) and their iNOS-catalysed
      oxidation to NO.
AB  - The binding of several alkyl- and aryl-guanidines and N-hydroxyguanidines to the
      oxygenase domain of inducible NO-synthase (iNOS(oxy)) was studied by UV/Vis
      difference spectroscopy. In a very general manner, monosubstituted guanidines
      exhibited affinities for iNOS(oxy) that were very close to those of the
      corresponding N-hydroxyguanidines. The highest affinities were observed for the
      natural substrates, L-arginine and N(omega)-hydroxy-L-arginine (K(d) at the
      microm level). The deletion of either the CO2H or the NH2 function of their amino
      acid moiety led to dramatic decreases in the affinity. However, alkylguanidines
      with a relatively small alkyl chain exhibited interesting affinities, the best
      being observed for a butyl chain (K(d) =20 microM). Arylguanidines also bound to
      iNOS(oxy), however, with lower affinities (K(d) > 250 microm). Many N-alkyl- and
      N-aryl-N'-hydroxyguanidines are oxidized by iNOS with formation of NO, whereas
      only few alkylguanidines led to significant production of NO under identical
      conditions, and all the arylguanidines tested to date were unable to lead to the
      production of NO. The k(cat) values of NO production from the oxidation by iNOS
      of the studied N-hydroxyguanidines were found to vary independently of their
      affinity for the protein. The k(cat) values determined for the two-step oxidation
      of alkylguanidines to NO were not clearly related to the K(d) of these substrates
      toward iNOS(oxy). However, there is a qualitative relationship between these
      k(cat) values and the apparent rate constants of dissociation of the complex
      between iNOS(oxy) and the corresponding N-alkyl-N'-hydroxyguanidine (k(off)
      (app)) that were determined by stopped-flow UV/Vis spectroscopy. These data
      indicate that a key factor for efficient oxidation of a guanidine by iNOS to NO
      is the ability of the corresponding N-hydroxyguanidine to bind to the active site
      without being too rapidly released before its further oxidation. This explains
      why 4,4,4-trifluorobutylguanidine is so far the best non-alpha-amino acid
      guanidine substrate of iNOS with formation of NO, because the k(off) (app) of the
      corresponding N-hydroxyguanidine is particularly low. This suggests that the
      rational design of guanidines as new NO donors upon in situ oxidation by NOSs
      should take into account both thermodynamic and kinetic characteristics of the
      interaction of the protein not only with the guanidine but also with the
      corresponding N-hydroxyguanidine.

PMID- 15955075
TI  - Conformational properties of bacterial DnaK and yeast mitochondrial Hsp70. Role
      of the divergent C-terminal alpha-helical subdomain.
AB  - Among the eukaryotic members of the Hsp70 family, mitochondrial Hsp70 shows the
      highest degree of sequence identity with bacterial DnaK. Although they share a
      functional mechanism and homologous co-chaperones, they are highly specific and
      cannot be exchanged between Escherichia coli and yeast mitochondria. To provide a
      structural basis for this finding, we characterized both proteins, as well as two
      DnaK/mtHsp70 chimeras constructed by domain swapping, using biochemical and
      biophysical methods. Here, we show that DnaK and mtHsp70 display different
      conformational and biochemical properties. Replacing different regions of the
      DnaK peptide-binding domain with those of mtHsp70 results in chimeric proteins
      that: (a) are not able to support growth of an E. coli DnaK deletion strain at
      stress temperatures (e.g. 42 degrees C); (b) show increased accessibility and
      decreased thermal stability of the peptide-binding pocket; and (c) have reduced
      activation by bacterial, but not mitochondrial co-chaperones, as compared with
      DnaK. Importantly, swapping the C-terminal alpha-helical subdomain promotes a
      conformational change in the chimeras to an mtHsp70-like conformation. Thus,
      interaction with bacterial co-chaperones correlates well with the conformation
      that natural and chimeric Hsp70s adopt in solution. Our results support the
      hypothesis that a specific protein structure might regulate the interaction of
      Hsp70s with particular components of the cellular machinery, such as Tim44, so
      that they perform specific functions.

PMID- 15955076
TI  - Determinants of the nucleocytoplasmic shuttling of muscle glycogen synthase.
AB  - Muscle glycogen synthase (MGS) presents a nuclear speckled pattern in primary
      cultured human muscle and in 3T3-L1 cells deprived of glucose and with depleted
      glycogen reserves. Nuclear accumulation of the enzyme correlates inversely with
      cellular glycogen content. Although the glucose-induced export of MGS from the
      nucleus to the cytoplasm is blocked by leptomycin B, and therefore mediated by
      CRM1, no nuclear export signal was identified in the sequence of the protein.
      Deletion analysis shows that the region comprising amino acids 555-633 of human
      MGS, which encompasses an Arg-rich cluster involved in the allosteric activation
      of the enzyme by Glc6P, is crucial for its nuclear concentration and aggregation.
      Mutation of these Arg residues, which desensitizes the enzyme towards Glc6P,
      interferes with its nuclear accumulation. In contrast, the known phosphorylation
      sites of MGS that regulate its activity are not involved in the control of its
      subcellular distribution. Nuclear human MGS co-localizes with the promyelocytic
      leukaemia oncoprotein and p80-coilin, a marker of Cajal bodies. The subnuclear
      distribution of MGS is altered by incubation with transcription inhibitors. These
      observations suggest that, in addition to its metabolic function, MGS may
      participate in nuclear processes.

PMID- 15955077
TI  - Modular usage of the HLA-DRA promoter in extra-hematopoietic and hematopoietic
      cell types of transgenic mice.
AB  - Class II MHC genes (for example, the human HLA-DRA gene) are expressed at the
      cell surface in many professional and nonprofessional antigen-presenting cells in
      a variety of anatomical locations. Here, we report about 13 mouse transgenic
      lines (11 of which have not been previously described) generated with four
      distinct sets of DRA transgenes carrying progressive, informative 5' and 3'
      deletions. DRA expression was assessed in B lymphocytes, dendritic cells,
      macrophages, and extra-hematopoietic cells (particularly kidney epithelial
      cells). A compact transcriptional unit was identified that efficiently directs
      DRA expression [both constitutive and interferon (IFN)-gamma induced] in extra
      hematopoietic tissues and dendritic cells. It extends from position -266 upstream
      of the transcription initiation site to position +119 downstream of the last DRA
      exon. The same fragment, however, did not efficiently direct IFN-gamma-induced
      DRA expression in macrophages, that required additional 5' sequences. Thus, IFN
      gamma uses distinct promoter segments and mechanisms to up-regulate class II in
      different cell lineages. In contrast to previous results in transgenic mice
      expressing murine class II transgenes, we were unable to generate reproducible
      patterns of HLA-DRA expression in B cells.

PMID- 15955081
TI  - Inflammation and cancer: is the link as simple as we think?

PMID- 15955082
TI  - Resurgent clinical science (and it's all about health).

PMID- 15955083
TI  - Stratum corneum moisturization at the molecular level: an update in relation to
      the dry skin cycle.

PMID- 15955085
TI  - Towards dissecting the pathogenesis of retinoid-induced hair loss: all-trans
      retinoic acid induces premature hair follicle regression (catagen) by
      upregulation of transforming growth factor-beta2 in the dermal papilla.
AB  - Diffuse hair loss ranks among the most frequent and psychologically most
      distressing adverse effects of systemic therapy with retinoids, which severely
      limits their therapeutic use even where clinically desired. Since the underlying
      mechanisms of retinoid-induced effluvium are as yet unknown, we have investigated
      the influence of the prototypic retinoid all-trans retinoic acid (ATRA,
      tretinoin) on the growth of human scalp hair follicles (HF) in culture. HF in the
      anagen VI stage of the hair cycle were cultured in the presence of 10(-8) or 10(
      10) M ATRA. Compared with controls, hair shaft elongation declined significantly
      already after 2 d in the ATRA-treated group, and approximately 80% of the ATRA
      treated HF had prematurely entered catagen-like stage at day 6, compared with 30%
      in the control group. This corresponded to an upregulation of apoptotic and a
      downregulation of Ki67-positive cells in ATRA-treated HF. Since transforming
      growth factor (TGF)-beta has been implicated as a key inducer of catagen, we next
      studied whether ATRA treatment had any effect on follicular expression. TGF-beta2
      immunoreactivity was detected in the outer root sheath of anagen VI scalp HF. In
      catagen follicles, TGF-beta2 was also expressed in the regressing epithelial
      strand. After 4 d of ATRA treatment, TGF-beta2 was significantly upregulated in
      anagen HF in the dermal papilla (DP) and the dermal sheath, 7, and TGF-beta
      neutralizing antibody partially abrogated at RA induced hair growth inhibition.
      Real-time PCR confirmed a significant upregulation of TGF-beta2 transcripts in
      ATRA-treated hair bulbs. This study is the first to provide direct evidence that
      ATRA can indeed induce a catagen-like stage in human HF and suggests that this
      occurs, at least in part, via upregulation of TGF-beta2 in the DP. Therefore,
      topical TGF-beta2/TGF-beta receptor II antagonists deserve to be explored for the
      prevention and management of retinoid-induced hair loss.

PMID- 15955084
TI  - Size polymorphisms in the human ultrahigh sulfur hair keratin-associated protein
      4, KAP4, gene family.
AB  - Hair keratin-associated proteins (KAP) are a major structural component of the
      hair fiber. In humans, five clusters of KAP genes have been identified, leading
      to the isolation of more than 80 individual KAP members. Of these, a cluster of
      high/ultrahigh sulfur KAP has been characterized on chromosome 17q12-21. Within
      this cluster, however, there was an incompletely sequenced region in which the
      ultrahigh sulfur KAP4 genes were located. A recently reported human bacterial
      artificial chromosome clone, AC100808, finally covered the gap, which enabled us
      to characterize the complete set of KAP4 genes in this cluster. Analysis of the
      nucleotide sequences of AC100808, together with PCR amplification, allowed us to
      identify numerous size polymorphisms in the KAP4 genes, which were mainly due to
      variations in the sequences encoding cysteine-rich repeat segments. Taken
      together, the data indicate that the polymorphic alleles of the KAP4 genes may
      have arisen through intragenic deletion and/or duplication of sequences encoding
      the repeat structures during evolution.

PMID- 15955086
TI  - Expression of perilipin A on the surface of lipid droplets increases along with
      the differentiation of hamster sebocytes in vivo and in vitro.
AB  - To clarify the involvement of perilipin, a lipid-droplet-surface protein
      associated with adipocytes and steroidogenic cells, in the differentiation of
      sebocytes, we investigated the expression of perilipin in sebaceous glands in
      vivo and in vitro. Perilipin was expressed in sebaceous glands of the hamster
      auricle in vivo and was localized at the surface of intracellular lipid droplets
      in differentiated hamster sebocytes in vitro. Western blot analysis showed that
      perilipin with a molecular weight of approximately 57 kDa, which was identical to
      that in differentiated mouse 3T3-L1 adipocytes, was detected in cultured
      sebocytes, indicating that sebaceous glands expressed perilipin A. In addition,
      the production of perilipin A in cultured sebocytes was transcriptionally
      augmented by sebocytic-lipogenesis stimulators, insulin, and 5alpha
      dihydrotestosterone, whereas it was decreased by a suppressor of sebocytic
      differentiation, epidermal growth factor. Furthermore, hamster sebocytes were
      found to express peroxisome proliferation-activating receptor alpha and gamma1,
      the activation of which by WY14643 and troglitazone, respectively, caused the
      transcriptional augmentation of perilipin A expression along with an increase in
      levels of triacylglycerols in lipid droplets in sebocytes. Therefore, these
      results provide novel evidence that the expression of perilipin A increases on
      the surface of intracellular lipid droplets augmented along with the
      differentiation of hamster sebocytes.

PMID- 15955087
TI  - Amphiregulin causes functional downregulation of adherens junctions in psoriasis.
AB  - Overexpression of amphiregulin (AR) has been linked to psoriasis in mouse and
      man. Since psoriasis is marked by hyperproliferation of keratinocytes and loss of
      epidermal barrier function with infiltration of inflammatory cells into the
      epidermis and dermis, we hypothesized that AR might contribute to the
      pathogenesis of psoriasis by affecting the integrity of cell-cell junctions. We
      find that there is a marked reduction of functional E-cadherin in psoriatic
      lesions from both INV-AR mice and individuals with psoriasis. Total E-cadherin
      levels are dramatically reduced in psoriatic lesions from INV-AR mice. Compared
      with normal skin, psoriatic lesions from individuals with psoriasis exhibit
      downregulation of the cytoskeletal-associated triton-insoluble pool of E-cadherin
      and the appearance of an 80 kDa ectodomain fragment in the cytoplasmic triton
      soluble pool. There is reduced immunohistochemical staining for E-cadherin in the
      basal epidermis of human psoriatic lesions. Moreover, there is enhanced
      transmigration of human neutrophils through polarized epithelial cell monolayers
      of MDCK cells after administration of AR, but not transforming growth factor
      alpha, further supporting a specific role for AR in the pathogenesis of
      psoriasis.

PMID- 15955088
TI  - CpG oligodeoxynucleotides prevent the development of scleroderma-like syndrome in
      tight-skin mice by stimulating a Th1 immune response.
AB  - Tight-skin (Tsk/+) mice develop a disease similar to human scleroderma,
      characterized by the spontaneous appearance of cutaneous hyperplasia, anti
      nuclear antibodies, and emphysema. T helper (Th) 2 cells secreting interleukin
      (IL)-4 are known to play a critical role in the etiopathogenesis of this disease.
      Th2-mediated responses can be blocked by treatment with synthetic
      oligodeoxynucleotides (ODN) containing immunomodulatory CpG motifs. Thus, we
      examined whether CpG ODN might be of therapeutic benefit in Tsk/+ mice.
      Administering CpG ODN to Tsk/+ mice every 3 wk starting at 1 wk of age abrogated
      skin fibrosis. This reduction in skin thickness persisted even after the
      cessation of therapy, and was accompanied by increased serum levels of IL-12 and
      an increased ratio of T cells available to secrete interferon-gamma rather than
      IL-4. CpG ODN therapy also reduced autoantibody production, but did not inhibit
      the incidence of lung emphysema. Delaying the initiation of CpG ODN treatment
      until 6 wk of age failed to prevent skin disease. These results indicate that by
      preferentially promoting the development of a Th1-biased immune milieu in young
      Tsk/+ mice, CpG ODN can ameliorate Th2-driven scleroderma-like syndrome.

PMID- 15955089
TI  - Topical application of 17beta-estradiol increases extracellular matrix protein
      synthesis by stimulating tgf-Beta signaling in aged human skin in vivo.
AB  - To investigate the effects of topically applied 17beta-estradiol on the
      expression of extracellular matrix proteins in aged human skin, 17beta-estradiol
      (0.01%) and its vehicle (70% propylene glycol, 30% ethanol) were applied to aged
      (68-82 y, eight females and five males) human buttock skin under occlusion for 2
      wk (three times per week). Topical 17beta-estradiol was found to increase the
      expression of type 1 procollagen mRNA and protein significantly in human aged
      skin in vivo. In addition, metalloproteinase (MMP-1 protein levels were reduced
      by topical 17beta-estradiol. The expressions of TGF-beta1, TGF-beta type II
      receptor, and Sma and Mad related (Smad)3 were increased by topical 17 beta
      estradiol in aged human skin, and TGF-beta1 neutralizing antibody inhibited
      17beta-estradiol-induced procollagen synthesis in cultured fibroblasts. We also
      found that the expressions of tropoelastin and fibrillin-1 mRNA and protein, and
      elastic fibers in aged skin were also increased by topical 17beta-estradiol.
      Topical 17beta-estradiol also increased keratinocyte proliferation and the
      epidermal thickness in aged human skin. We also observed the same effects of
      topical 17beta-estradiol in young skin. In conclusion, our results suggest that
      topical 17beta-estradiol treatment may improve the cutaneous function of aged
      human skin by improving the connective tissue and increasing epidermal thickness.

PMID- 15955090
TI  - Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate
      transforming growth factor-beta-induced expression of connective tissue growth
      factor in human fibroblasts.
AB  - Connective tissue growth factor (CTGF) is secreted by fibroblasts stimulated with
      transforming growth factor-beta (TGF-beta). CTGF is a potent enhancer of
      fibroblast proliferation, chemotaxis, and extracellular matrix deposition, and it
      is thought to mediate some of the fibrogenic effects of TGF-beta. Here, we have
      elucidated signaling pathways involved in regulating the TGF-beta-induced
      production of CTGF in primary fibroblasts. TGF-beta induced the expression of
      CTGF messenger RNA and protein in human gingival fibroblasts after 2 h of
      treatment. Adenoviral overexpression of Smad3 enhanced the TGF-beta-elicited
      expression of CTGF, whereas Smad7 and dominant-negative Smad3 suppressed the
      effects of TGF-beta on CTGF and Cyr61 expression. Pre-treatment of cells with
      PD98059, an inhibitor for extracellular signal-regulated kinase (ERK)1/2
      activator mitogen-activated protein kinase (MAPK)/ERK kinase (MEK)1, potently
      inhibited the TGF-beta-induced expression of CTGF. Furthermore, co-expression of
      Smad3 with constitutively active MEK1 resulted in potent induction of CTGF
      production without exogenous TGF-beta stimulation. Together, these results
      demonstrate that Smad3 and ERK1/2 coordinately mediate TGF-beta-induced release
      of CTGF by fibroblasts. It is conceivable that the crosstalk between Smad3 and
      ERK1/2 signaling cascades plays an important role in regulating CTGF expression,
      e.g., in wound repair and tissue fibrosis and could be exploited in therapeutic
      targeting of fibrotic conditions.

PMID- 15955091
TI  - A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted
      by a mosaic sire.
AB  - A mechanobullous skin disorder was identified in the progeny of a 3-y-old
      Friesian-Jersey crossbred bull. The condition presented as loss of skin and
      mucosa from contact areas and inflammation. Examination of skin samples under
      light microscopy revealed separation of the epidermis from the dermis. Electron
      microscopic analysis refined the site of cleavage to above the basement membrane
      involving lysis of basal keratinocytes. These observations were consistent with
      the simplex form of epidermolysis bullosa (EB) in humans. Candidate genes based
      on human gene mutations were assessed, resulting in keratin 5 being identified as
      the most likely candidate gene. The sequence of bovine keratin 5 was established
      and sequencing led to identification of a G to A substitution in all affected
      animals. This mutation leads to an amino acid change of glutamic acid to lysine
      in the final E (478) of the KLLEGE motif of the protein. The sire carried a de
      novo mutation and was mosaic, explaining his asymptomatic status and the less
      than expected frequency of affected offspring. Remarkably, the same mutation has
      been previously described in EB simplex in humans.

PMID- 15955092
TI  - Genetics of psoriasis in Iceland: evidence for linkage of subphenotypes to
      distinct Loci.
AB  - Psoriasis is a chronic inflammatory skin disease with overlapping subphenotypes.
      It has a strong complex genetic component, but has been problematic to
      identifying significant loci. We evaluated 1000 patients with chronic plaque
      psoriasis and documented several subphenotypes. Here we report results of genome
      wide linkage scans for psoriasis genes in 238 Icelandic families with 874
      patients. MHC linkage was confirmed with LOD score of 10.9. When the entire
      cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed
      on 16q and 4q, respectively. Stratification into subphenotypes revealed
      additional loci with LOD scores exceeding or approaching significance. A LOD
      score of 5.7 appeared on 16q in PsA patients with analysis conditioned on
      parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred
      at or older than 17 y, our median cohort age. This locus was defined by a marker
      near one reportedly displaying significant linkage in a Chinese psoriasis
      population and near suggestive linkage in a Caucasian population. A LOD of 3.0
      was observed on 10q when disease onset occurred in the scalp. Furthermore,
      clinical stratification either revealed or increased LOD scores when compared to
      unstratified analysis and some coincided with previous reports.

PMID- 15955093
TI  - Mutation analysis of the ADAR1 gene in dyschromatosis symmetrica hereditaria and
      genetic differentiation from both dyschromatosis universalis hereditaria and
      acropigmentatio reticularis.
AB  - Dyschromatosis symmetrica hereditaria (DSH) (also called "reticulate
      acropigmentation of Dohi") is a pigmentary genodermatosis of autosomal dominant
      inheritance. We have clarified for the first time four pathological mutations of
      the double-stranded RNA-specific adenosine deaminase gene (ADAR1 or DSRAD) in
      four DSH pedigrees. In this paper, we report 16 novel mutations containing six
      missense substitutions (p.V906F, p.K1003R, p.G1007R, p.C1036S, p.S1064F,
      p.R1078C), two splice site mutations (IVS2+2T>G, IVS8+2T>A), six frameshift
      mutations (p.H216fs, p.K433fs, p.G507fs, p.P727fs, p.V955fs, p.K1201fs), and two
      nonsense mutations (p.R426X, p.Q600X) found in Japanese patients with DSH. We did
      not establish any clear correlation between the clinical phenotypes and the
      genotypes of ADAR1 gene mutations in our examination of 16 cases plus four
      pedigrees. None of the different mutations identified in our studies of 20 cases
      suggested any founder effect. Furthermore, we did not identify any mutations in
      the ADAR1 gene of three patients with dyschromatosis universalis hereditaria or
      three patients with acropigmentatio reticularis, indicating that the two diseases
      are completely different from DSH, although they have sometimes been suggested to
      be phenotypical variations of DSH.

PMID- 15955094
TI  - Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix
      deposition of mutant tropoelastin.
AB  - Cutis laxa (CL) is a heterogeneous group of genetic and acquired disorders with
      at least two autosomal dominant forms caused by mutations in the elastin and
      fibulin-5 genes, respectively. To define the molecular basis of CL in patients
      negative for point mutations in the elastin gene, metabolic labeling and
      immunoprecipitation experiments were used to study the synthesis of elastin in
      dermal fibroblasts. In addition to the normal 68 kDa tropoelastin (TE) protein,
      an abnormal, 120 kDa polypeptide was detected in the proband and her affected
      daughter in a CL family characterized by hernias and unusually severe and early
      onset pulmonary disease including bronchiectasis and pulmonary emphysema.
      Mutational and gene expression studies established that affected individuals in
      this family carried a partial tandem duplication in the elastin locus.
      Immunoprecipitation experiments showed that the mutant TE was partially secreted
      and partially retained intracellularly. A polyclonal antibody raised against a
      unique peptide in the mutant TE molecule showed both intracellular and matrix
      staining. We conclude that elastin mutations can cause CL associated with a
      severe pulmonary phenotype. Synthesis of abnormal TE may interfere with elastic
      fiber function through a dominant-negative or a gain of function mechanism.

PMID- 15955095
TI  - A novel nonsense mutation and polymorphisms in the mouse hairless gene.
AB  - A novel autosomal recessive mutation arose spontaneously in a breeding colony of
      Chinese Kunming mice. The characteristics of these mutant mice include
      progressive irreversible hair loss soon after birth, rhinocerotic appearance, and
      shorter life span. Histological evaluation of skin revealed the homogeneous
      enlargement of utriculi, and the formation of several rows of large cysts.
      Sequencing the complete cDNA of the hairless gene identified two polymorphisms
      and a homozygous transition for a G-->A at nucleotide position 3110 (exon 12)
      leading to the substitution of tryptophan by a nonsense codon, designated W911X.
      This allele was named rhinocerotic and short-lived, with the symbol hr(rhsl).
      Addition of hairless gene mutation into the expanding hairless mutation database
      allows further development of genotype/phenotype correlations towards
      understanding inherited atrichia.

PMID- 15955096
TI  - Transcriptional regulation of ATP2C1 gene by Sp1 and YY1 and reduced function of
      its promoter in Hailey-Hailey disease keratinocytes.
AB  - Hailey-Hailey disease (HHD) is a blistering skin disease caused by malfunction of
      the Ca2+-dependent ATPase, ATP2C1. In this study, key regulatory regions
      necessary for the expression of the gene encoding human ATP2C1 were investigated.
      The transient reporter assay demonstrated that region +21/+57 was necessary for
      activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay
      demonstrated that the region was recognized by the transcription factors, Sp1 and
      YY1. In accordance with this result, when Sp1 or YY1 was overexpressed in
      keratinocytes, an obvious increase in ATP2C1 promoter activity was observed,
      which was in contrast with the case where a mutant promoter lacking the binding
      sites for Sp1 and YY1 was used as the reporter. Ca2+-stimulation signal increased
      nuclear Sp1 proteins and ATP2C1 mRNA levels in normal keratinocytes. In contrast,
      both these increases were suppressed in keratinocytes from HHD patients. These
      results indicate that Sp1 and YY1 transactivate the human ATP2C1 promoter via cis
      enhancing elements and that incomplete upregulation of ATP2C1 transcription
      contributes to the keratinocyte-specific pathogenesis of HHD. This is a report
      describing the regulation of the expression of ATP2C1.

PMID- 15955097
TI  - CD34+ cells in the peripheral blood transport herpes simplex virus DNA fragments
      to the skin of patients with erythema multiforme (HAEM).
AB  - Herpes simplex virus (HSV)-associated erythema multiforme (HAEM) is a recurrent
      disease characterized by the presence and expression of HSV DNA fragments in
      lesional skin. Our studies examined the mechanism of viral DNA transport to the
      skin of HAEM patients. CD34+ cells were isolated from the blood of normal
      subjects and HSV and HAEM patients during acute lesions and at quiescence. They
      were cultured with cytokines that favor their differentiation into Langerhans
      cells (LC) precursors (CD1a+/CD14-) and examined for HSV replication, HSV-induced
      cellular alterations, viral DNA fragmentation, and clearance. CD34+ cells from
      all study groups were non-permissive for HSV replication but infection favored
      their differentiation into CD1a+/CD14- LC precursors and upregulated E-cadherin
      expression, thereby assisting LC targeting to the skin. Only HAEM patients had
      CD34+ cells that retained viral DNA fragments, notably polymerase DNA, for at
      least 7 d of in vitro culture. The percentages of circulating CD34+ (and
      CD34+/CLA+) cells were significantly higher in HAEM patients at the time of acute
      lesions. A similar increase was not seen for HSV patients. The data are the first
      report implicating CD34+ cells in HAEM pathogenesis, likely by transporting HSV
      DNA fragments to lesional skin.

PMID- 15955098
TI  - Human keratinocytes respond to interleukin-18: implication for the course of
      chronic inflammatory skin diseases.
AB  - Interleukin (IL)-18 has been described to play a role in several inflammatory
      skin diseases such as eczema and psoriasis. In this study, we aimed to elucidate
      keratinocytes as potential targets for IL-18 effects. In human primary
      keratinocytes expression of IL-18Ralpha as well as responses to IL-18 were
      determined. In keratinocytes freshly isolated from skin biopsies of lesional
      atopic dermatitis or psoriasis, we observed a significantly higher expression of
      the IL-18Ralpha as compared with keratinocytes from normal donors. A marked
      upregulation was induced in vitro upon stimulation with interferon
      (IFN)gamma+tumor necrosis factor (TNF)alpha or poly I:C. IL-4 led to
      downregulation of IL-18Ralpha. IL-18-induced CXCL10/IP-10 production in freshly
      isolated keratinocytes from lesional psoriasis as well as in cultured normal
      keratinocytes. Furthermore, IL-18 upregulated major histocompatibility complex
      (MHC) class II expression on IFNgamma-stimulated keratinocytes. This was of
      functional significance as verified in coculture experiments with CD4+ T cells in
      the presence of superantigen. T cells produced significant amounts of IFNgamma
      after coculture with IL-18-induced MHC class II expressing keratinocytes. In
      conclusion, we have shown that keratinocytes functionally respond to IL-18 with
      upregulation of MHC II and production of the chemokine CXCL10/IP-10. These
      findings further support an important role of IL-18 in inflammatory skin diseases
      in the epidermal compartment.

PMID- 15955099
TI  - Additional evidence that pityriasis rosea is associated with reactivation of
      human herpesvirus-6 and -7.
AB  - To elucidate the role of human herpesvirus (HHV)-6 and -7 (HHV-7) in pityriasis
      rosea (PR), we measured their DNA load in plasma, peripheral blood mononuclear
      cells (PBMC), and tissues using a calibrated quantitative real-time PCR assay. We
      also studied HHV-6- and HHV-7-specific antigens in skin by immunohistochemistry
      and anti-HHV-7 neutralizing activity using a syncytia-inhibition test. Plasma and
      PBMC were obtained from 31 PR patients (14 children, 17 adults), 12 patients with
      other dermatites, and 36 blood donors. Skin biopsies were obtained from 15 adults
      with PR and 12 with other dermatites. HHV-6 and HHV-7 DNA were detected in 17%
      and in 39% of PR plasmas, respectively, but in no controls. HHV-7 viremia was
      associated with a higher PBMC load and, in adults, with systemic symptoms. HHV-7,
      but not HHV-6, levels in PBMC were higher in PR patients than in controls. HHV-6
      and HHV-7 antigens were found only in PR skin (17% and 67% of patients analyzed,
      respectively), indicating a productive infection. Syncytia-neutralizing
      antibodies were found in PR patients and controls, but their titers were lower in
      patients with HHV-7 viremia. These data confirm the causal association between PR
      and active HHV-7 or, to a lesser extent, HHV-6 infection.

PMID- 15955100
TI  - Role of the chemokine receptor CCR4 and its ligand thymus- and activation
      regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus
      erythematosus.
AB  - Skin-infiltrating T lymphocytes are thought to play a major role in the
      pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we
      investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus-
      and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in
      inflamed skin of patients with CLE. We found significant numbers of CCR4+ T
      lymphocytes in the skin of all patients with CLE. Interestingly, a subset of
      patients with disseminated scarring skin involvement were characterized by both
      lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal
      and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T
      cells invading basal layers of the epidermis where keratinocytes showed apoptotic
      death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and
      elevated in the serum of CLE patients. The functional relevance of lymphocytic
      CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration
      assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the
      pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4
      appear to be involved in scarring subtypes of CLE.

PMID- 15955101
TI  - Salivary lactoferrin is recognized by the human herpesvirus-8.
AB  - Human herpesvirus-8 (HHV-8) is commonly detected in all epidemiologic forms of
      Kaposi's sarcoma. Despite the broad cellular tropism of HHV-8, studies on mucosal
      shedding of HHV-8 have shown that infectious particles are restricted to saliva
      isolated from the oropharynx. We used biotinylated purified HHV-8 particles in a
      direct binding assay to whole clarified human salivary samples isolated from HHV
      8-infected and uninfected individuals. We found that the major binding activity
      was carried out by a protein of 78-kDa size, which was further characterized as
      human lactoferrin (hLf) using 2-D electrophoresis and MALDI-ToF analysis.
      Preliminary comparison of HHV-8 binding activity of 76 salivary samples from HHV
      8-infected and uninfected individuals showed that 7.8% of the uninfected
      population exhibited a form of Lf not recognized by HHV-8. Deglycosylation of hLf
      by PNGase F did not reduce HHV-8 binding activity, whereas endoproteinase
      cleavage of native hLf generated a non-glycosylated 8-kDa peptide recognized by
      HHV-8 particles and was located at the position Ala606-Tyr679 in the native hLf
      amino acid sequence, corresponding to the C-terminal region of the glycoprotein.
      This work identify the lactoferrin in saliva as a ligand for HHV-8 and suggests
      that this glycoprotein could be used as a carrier for the viral particles.

PMID- 15955102
TI  - Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase
      and lipase.
AB  - Retinoic acid influences epidermal morphology and function through its ability to
      control transcription. Because the circulation presents the epidermis with
      micromolar amounts of retinol that can be converted to retinoic acid, regulating
      retinol access is imperative. In keratinocytes the majority of retinol is
      sequestered as long chain fatty acid esters. Although much has been learned about
      the major esterifying enzyme, little is known about the hydrolase that accesses
      retinol from its storage depot. Murine carboxylesterases and hormone sensitive
      lipase have been shown to have this activity. We found that their in vitro
      sensitivity to bis-p-nitrophenyl phosphate (BNPP), however, was not shared by the
      epidermal hydrolase activity. We therefore produced and screened two keratinocyte
      cDNA expression libraries and identified a previously sequenced gene (GS2) as a
      keratinocyte retinyl ester (RE) hydrolase insensitive to BNPP. The enzyme also
      catalyzes fattyacyl CoA-dependent and -independent retinol esterification. The
      hydrolysis reaction is greater at neutral pH, whereas the esterification reaction
      is greater at acidic pH. These activities are consistent with the increased RE
      content that accompanies epidermal maturation. In addition, this enzyme utilizes
      triolein as substrate and generates diacylglyceride and free fatty acid.

PMID- 15955103
TI  - Counter-regulation of interleukin-1alpha (IL-1alpha) and IL-1 receptor antagonist
      in murine keratinocytes.
AB  - Interleukin-1alpha (IL-1alpha) is a potent proinflammatory cytokine
      constitutively expressed by keratinocytes, which also synthesize a specific
      inhibitor of IL-1 activity, intracellular IL-1 receptor antagonist (IL-1ra).
      Although homeostatic regulation of the IL-1 system in keratinocytes has long been
      suspected, there is currently little evidence for this. To explore this issue,
      the PAM212 murine keratinocyte cell line was exposed to increasing concentrations
      of either IL-1alpha or IL-1ra and the opposing ligand was assessed by ELISA.
      Release of IL-1ra was induced following stimulation by murine IL-1alpha in a
      concentration-dependent manner and, conversely, IL-1ra stimulation increased IL
      1alpha release. To determine whether a similar homeostatic circuit operates in
      vivo, epidermis from transgenic mice in which overexpression of IL-1alpha or IL
      1ra was targeted to keratinocytes was analyzed. Epidermal sheets derived from IL
      1alpha transgenic mice released eight times more IL-1ra than those from wild-type
      mice following ex vivo culture and similarly, IL-1alpha release was increased 3-4
      fold in epidermal sheets derived from IL-1ra transgenic epidermis, Use of
      specific neutralizing antibodies against type I and type II IL-1 receptors
      indicated that the counter-regulation mechanism is mediated extracellularly
      through the type I IL-1 receptor alone. Taken together, these observations
      provide the first demonstration of mutual counter-regulation of IL-1 receptor
      ligands in keratinocytes.

PMID- 15955104
TI  - Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic
      epidermis and downregulation of NF-kappaB in response to treatment with
      etanercept.
AB  - Etanercept, a recombinant human tumor necrosis factor (TNF) receptor fusion
      protein, is FDA approved for psoriasis and psoriatic arthritis. TNFalpha
      increases the synthesis of proinflammatory cytokines and leads to the activation
      of multiple signaling pathways, including nuclear factor kappa B (NF-kappaB). The
      Rel/NF-kappaB transcription factors play a central role in numerous cellular
      processes, including the stress response and keratinocyte proliferation and
      differentiation. Utilizing a phosphorylation-specific antibody, we examined the
      expression of active nuclear NF-kappaB/RelA via immunohistochemistry in normal
      skin, non-lesional psoriatic skin, lesional psoriatic skin, and lesional skin
      from patients treated with etanercept. There was no expression of active nuclear
      NF-kappaB in the normal epidermis, whereas a basal level of constitutive active
      phosphorylated NF-kappaB/RelA was present in uninvolved epidermis from psoriasis
      patients. There was also significant upregulation of active phosphorylated NF
      kappaB/RelA in the epidermis from psoriatic plaques. Serial biopsies from
      psoriasis patients treated with etanercept at 1, 3, and 6 mo demonstrated a
      significant downregulation of phosphorylated NF-kappaB/RelA, which correlated
      with decreases in epidermal thickness, restoration of normal markers of
      keratinocyte differentiation, and clinical outcomes. These data suggest that
      activation of NF-kappaB plays a significant role in the pathogenesis of psoriasis
      and that a potential mechanism of action for TNF-targeting agents is
      downregulation of NF-kappaB transcriptional activity.

PMID- 15955105
TI  - Inverse regulation of the nuclear factor-kappaB binding to the p53 and
      interleukin-8 kappaB response elements in lesional psoriatic skin.
AB  - Nuclear factor-kappaB (NF-kappaB) is an inducible nuclear transcription factor
      regulating a range of cellular processes. An imbalance of the DNA binding
      activity of NF-kappaB may, therefore, be part of the pathophysiological
      mechanisms in psoriasis. The purpose of this study was to determine the NF-kappaB
      DNA binding activity in psoriatic skin using three different kappaB sites and to
      determine how DNA binding activity was modulated by the anti-psoriatic drug
      calcipotriol. By electrophoretic mobility shift assay, we demonstrated that the
      NF-kappaB DNA binding to the p53 kappaB site was decreased, whereas the NF-kappaB
      DNA binding to the interleukin-8 (IL-8) kappaB site was increased in lesional
      psoriatic skin compared with non-lesional psoriatic skin. No regulation was seen
      on the NF-kappaB DNA binding to the major histocompatibility complex class I
      kappaB site. These changes were paralleled by a similar decrease in p53
      expression and an increase in IL-8 expression in involved psoriatic skin compared
      with uninvolved skin as determined by quantitative RT-PCR. The alteration in NF
      kappaB DNA binding activity was neither accompanied by any change in the
      expression of the inhibitor kappaB (IkappaB) kinases, IKKalpha, IKKbeta, and
      IKKgamma nor in the expression of the NF-kappaB inhibitor proteins, IkappaBalpha
      and IkappaBbeta. Immunofluorescence analysis revealed that p65 was sequestered in
      the cytoplasm of keratinocytes, whereas p50 exhibited a cytoplasmic as well as a
      nuclear localization. Interestingly, this distribution of p50 and p65 was similar
      in lesional and non-lesional psoriatic skin. Topical application of calcipotriol
      to lesional psoriatic skin for 4 d resulted in increased NF-kappaB binding to the
      p53 kappaB site and decreased NF-kappaB binding to the IL-8 kappaB site. Taken
      together, our data demonstrate that the NF-kappaB DNA binding activity is
      regulated in a specific manner in psoriatic skin depending on the kappaB sites
      investigated, and that topical treatment of psoriatic skin normalizes the
      abnormal NF-kappaB binding activity seen in lesional psoriatic skin.

PMID- 15955106
TI  - The non-receptor-associated tyrosine kinase Syk is a regulator of metastatic
      behavior in human melanoma cells.
AB  - Melanoma is one of the most aggressive neoplastic transformations and
      characterized by a high metastatic potential. The current study was performed to
      assess the impact of "spleen tyrosine kinase" (Syk), a non-receptor-associated
      tyrosine kinase, on growth and metastatic behavior of melanoma cells in vitro and
      in a severe combined immunodeficient (SCID)-mouse/human-melanoma
      xenotransplantation model in vivo. Syk was expressed in melanocytes but was found
      to be downregulated in melanoma cells. Vector-driven expression of Syk in two
      different melanoma cell lines did not influence growth speed, but significantly
      reduced the invasive growth potential of both cell lines in a Matrigel assay in
      vitro. In a SCID-mouse/human melanoma xenotransplantation model, Syk expressing
      Mel-Juso cells exhibited delayed and reduced tumor growth. After intravenous as
      well as subcutaneous injection of tumor cells, Syk-transfected cells formed
      significantly fewer metastatic tumor lesions than control cells. The presented
      data define Syk as a novel regulator of metastatic behavior of melanoma cells.

PMID- 15955107
TI  - Clusterin regulates drug-resistance in melanoma cells.
AB  - Clusterin has recently been shown to act as an antiapoptotic protein that confers
      drug-resistance in models of epithelial tumors. The aim of our work was to
      provide an insight into a possible role of clusterin in the regulation of drug
      resistance in melanoma. In tissue samples, clusterin expression was low in nevi,
      but high in primary melanoma and melanoma metastases. Clusterin was also strongly
      expressed in melanoma cell lines, but was barely detectable in cultured
      melanocytes. To elucidate a possible role of clusterin in drug-resistance of
      melanoma, clusterin expression was regulated by either plasmid-driven
      overexpression or by antisense-mediated downregulation. Clusterin overexpression
      was associated with an increase in drug-resistance, i.e., with an increased
      survival of melanoma cells in the presence of cytotoxic drugs. In contrast,
      downregulation of clusterin by 2'-O-(2-methoxy)ethyl (2'MOE)-modified antisense
      oligonucleotides (AS-ODN) directed against clusterin mRNA significantly reduced
      drug-resistance, i.e., decreased survival of melanoma cells in the presence of
      cytotoxic drugs. To evaluate the effects of clusterin-antisense treatment in
      vivo, we applied an SCID-mouse/human-melanoma xenotransplantation model. Pre
      treatment of mice with the 2'MOE-modified clusterin AS-ODN was associated with a
      significantly improved tumor response to dacarbazine as compared with animals
      pretreated with a scrambled control oligonucleotide. Taken together, we show that
      clusterin is strongly expressed in melanoma. Downregulation of clusterin reduces
      drug-resistance, i.e., reduces melanoma cell survival in response to cytotoxic
      drugs in vitro and in vivo. Thus, reducing clusterin expression may provide a
      novel tool to overcome drug-resistance in melanoma.

PMID- 15955108
TI  - The effect of solar-simulated radiation on the elicitation phase of contact
      hypersensitivity does not differ between controls and patients with polymorphic
      light eruption.
AB  - It has been suggested that polymorphic light eruption (PLE) is characterized by a
      failure of ultraviolet radiation (UVR)-induced immunosuppression, resulting in a
      type-IV hypersensitivity response to photoinduced antigens. We measured the
      effect of solar-simulated radiation (SSR) on the elicitation phase of contact
      hypersensitivity to 2,4-dinitrochlorobenzene (DNCB), in ten PLE patients and 11
      controls. Subjects were given a sensitizing dose of DNCB, and 3 wk later were
      exposed to 0.75 and 2 minimum erythema doses (MED) of SSR on the upper inner arm.
      Immediately and 24 h later these sites, and a non-irradiated control site, were
      challenged with DNCB. The resulting increase in skin thickness was measured with
      high-frequency ultrasound. Overall, 2 MED caused 17%-20% suppression of
      elicitation responses (compared with 93% suppression of sensitization reported
      previously), but the effect of SSR varied greatly between subjects, with some
      subjects showing potentiated responses, which may be of relevance to false
      positive reactions in photopatch testing. In a repeated measures general linear
      model, SSR overall caused significant suppression of responses (p<0.001); there
      was less suppression in older subjects (p=0.009) but there was no significant
      difference between PLE patients and age-matched normal controls. These results
      contrast with our previous finding of a resistance to UVR-induced suppression of
      sensitization to DNCB in PLE. This difference may reflect the greater importance
      of Langerhans cells in the sensitization phase, and is consistent with the
      hypothesis that PLE arises from impaired suppression of Langerhans cell
      activation or migration.

PMID- 15955109
TI  - Ultraviolet radiation-induced impairment of tumor rejection is enhanced in
      xeroderma pigmentosum a gene-deficient mice.
AB  - Xeroderma pigmentosum (XP)A gene-deficient mice display dermatologic
      abnormalities similar to human XP, such as enhanced ultraviolet (UV)-induced
      acute inflammation and high incidence of UVB-induced skin cancer. We have
      previously reported that UVB-induced immunosuppression of contact
      hypersensitivity was greatly enhanced in XPA mice. In the present study, we
      examined the effects of UVB radiation on tumor rejection in XPA mice. Tumor cells
      established from UVB-induced squamous cell carcinoma in XPA mice were injected
      subcutaneously. No difference in the development of tumors was observed between
      the non-irradiated XPA and wild-type mice. Tumors developed, grew in size, and
      reached the maximum at 7-10 d after the inoculation. Thereafter, all tumors
      decreased in size and were completely rejected by 4 wk in both strains of mice.
      When tumor cells were inoculated into the skin that had been irradiated with 50
      150 mJ per cm2 of UVB, tumor grew in 60% (12 of 20) of the XPA mice, but only in
      4% (one of 23) of wild-type mice. Phenotyping of tumor-infiltrating cells
      revealed that the migration of natural killer cells and CD8+ T cells was
      inhibited in UVB-irradiated XPA mice. These data suggest that enhanced UVB
      induced impairment of tumor rejection could be partially involved in the cancer
      development of XP patients.

PMID- 15955110
TI  - Role of p38 MAPK in UVB-induced inflammatory responses in the skin of SKH-1
      hairless mice.
AB  - The p38 mitogen-activated protein kinase (MAPK) signaling pathway is activated by
      numerous inflammatory mediators and environmental stresses. We assessed the
      effects of ultraviolet B (UVB) on the p38 MAPK pathway and determined whether
      cyclooxygenase (COX)-2 expression is downstream of this kinase in the skin of UVB
      irradiated SKH-1 mice. SKH-1 mice were irradiated with a single dose of UVB (360
      mJ per cm2), and activation of the epidermal p38 MAPK pathway was assessed. UVB
      induced phosphorylation of p38 MAPK occurred in a time-dependent manner.
      Phosphorylation of MAPK-activated protein kinase-2 (MAPKAPK-2) also was detected
      and correlated with an increase in its kinase activity. Phosphorylation of heat
      shock protein 27 (HSP27), a substrate for MAPKAPK-2, also was detected post
      irradiation. Oral administration of the p38 inhibitor, SB242235, prior to UVB
      irradiation, blocked activation of the p38 MAPK cascade, and abolished MAPKAPK-2
      kinase activity and phosphorylation of HSP27. Moreover, SB242235 inhibited
      expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL
      8) and COX-2. Our data demonstrate that UVB irradiation of murine skin activates
      epidermal p38 MAPK signaling and induces a local pro-inflammatory response.
      Blockade of the p38 MAPK pathway may offer an effective approach to reducing or
      preventing skin damage resulting from acute solar radiation.

PMID- 15955111
TI  - Mechanisms of skin tanning in different racial/ethnic groups in response to
      ultraviolet radiation.
AB  - Ultraviolet radiation stimulates pigmentation in human skin, but the mechanism(s)
      whereby this increase in melanin production (commonly known as tanning) occurs is
      not well understood. Few studies have examined the molecular consequences of UV
      on human skin of various racial backgrounds in situ. We investigated the effects
      of UV on human skin of various races before and at different times after a single
      1 minimal erythemal dose UV exposure. We measured the distribution of DNA damage
      that results, as well as the melanin content/distribution and the expression of
      various melanocyte-specific genes. The density of melanocytes at the
      epidermal:dermal junction in different types of human skin are remarkably similar
      and do not change significantly within 1 wk after UV exposure. The expression of
      melanocyte-specific proteins (including TYR (tyrosinase), TYRP1 (tyrosinase
      related protein 1), DCT (tyrosinase-related protein 2), MART1 (melanoma antigens
      recognized by T-cells) gp100 (Pmel17/silver), and MITF (micropthalmia
      transcription factor)) increased from 0 to 7 d after UV exposure, but the melanin
      content of the skin increased only slightly. The most significant change,
      however, was a change in the distribution of melanin from the lower layer upwards
      to the middle layer of the skin, which was more dramatic in the darker skin.
      These results provide a basis for understanding the origin of different skin
      colors and responses to UV within different races.

PMID- 15955112
TI  - SCN9A mutations define primary erythermalgia as a neuropathic disorder of voltage
      gated sodium channels.
AB  - Primary erythermalgia is a rare disorder characterized by recurrent attacks of
      red, warm and painful hands, and/or feet. We previously localized the gene for
      primary erythermalgia to a 7.94 cM region on chromosome 2q. Recently, Yang et al
      identified two missense mutations of the sodium channel alpha subunit SCN9A in
      patients with erythermalgia. The presence of voltage-gated sodium channels in
      sensory neurons is thought to play a crucial role in several chronic painful
      neuropathies. We examined four different families and two sporadic cases and
      detected missense sequence variants in SCN9A to be present in primary
      erythermalgia patients. A total of five of six mutations were located in highly
      conserved regions. One family with autosomal dominantly inherited erythermalgia
      was double heterozygous for two separate SCN9A mutations. These data establish
      primary erythermalgia as a neuropathic disorder and offers hope for treatment of
      this incapacitating painful disorder.

PMID- 15955115
TI  - Visceral fat and respiratory complications.

PMID- 15955116
TI  - Development and application of rodent models for type 2 diabetes.
AB  - The increasing worldwide incidence of diabetes in adults constitutes a global
      public health burden. It is predicted that by 2025, India, China and the United
      States will have the largest number of people with diabetes. According to the
      2003 estimates of the International Diabetes Federation, the diabetes mellitus
      prevalence in the USA is 8.0% and approximately 90-95% of diabetic Americans have
      type 2 diabetes - about 16 million people. Type 2 diabetes is a complex,
      heterogeneous, polygenic disease characterized mainly by insulin resistance and
      pancreatic beta-cell dysfunction. Appropriate experimental models are essential
      tools for understanding the molecular basis, pathogenesis of the vascular and
      neural lesions, actions of therapeutic agents and genetic or environmental
      influences that increase the risks of type 2 diabetes. Among the animal models
      available, those developed in rodents have been studied most thoroughly for
      reasons such as short generation time, inherited hyperglycaemia and/or obesity in
      certain strains and economic considerations. In this article, we review the
      current status of most commonly used rodent diabetic models developed
      spontaneously, through means of genetic engineering or artificial manipulation.
      In addition to these models, the Psammomys obesus, rhesus monkeys and many other
      species are studied intensively and reviewed by Shafrir, Bailey and Flatt and
      Hansen.

PMID- 15955117
TI  - Genetic and clinical characteristics of maturity-onset diabetes of the young.
AB  - Genetic factors play an important role in various forms of diabetes mellitus
      (DM), but inheritance is complex and interacts with environmental factors.
      Although in most cases type 2 DM (T2DM) and T1DM are polygenic disorders, several
      monogenic forms have been identified. Among them, maturity-onset diabetes of the
      young (MODY) has been the most intensively investigated. MODY is a group of six
      different forms of monogenic diabetes, characterized by insulin secretion defects
      in pancreatic beta-cells, supposed to be responsible for 2-5% of all cases of
      diabetes. The most common are MODY2 and MODY3, caused by mutations in the genes
      encoding glucokinase and hepatocyte nuclear factor 1-alpha respectively. MODY2 is
      characterized by glucose sensing defects, leading to an increase in insulin
      secretion threshold. This causes lifelong sustained and mild hyperglycaemia from
      birth, most often in non-diabetic levels. Diagnosis is incidental in most cases.
      These patients are asymptomatic, seldom need treatment and rarely present chronic
      complications. MODY3 is characterized by a severe insulin secretion defect in
      response to glucose. Diagnosis is made usually in adolescence and early
      adulthood, often by osmotic symptoms. Hyperglycaemia is progressive, and patients
      frequently need treatment with oral drugs or insulin some time in their follow
      up. This group seems to have a marked sensitivity to sulphonylureas compared to
      other types of diabetes. The recognition of MODY as a monogenic disorder and a
      thorough understanding of its pathophysiology are important for correct diagnosis
      and treatment, with great impact on prognosis. Besides, the study of these forms
      of diabetes brings important contributions to the understanding of glucose
      homeostasis as a whole.

PMID- 15955118
TI  - The appetite-suppressant effect of nicotine is enhanced by caffeine.
AB  - AIM: To test whether the anorectic effect of nicotine may be amplified by
      caffeine. METHODS: Chewing gums with nicotine and caffeine were administered to
      12 healthy young men of normal weight. Different combinations of 0, 1 or 2 mg of
      nicotine and 0, 50 or 100 mg of caffeine were applied during a 2-h period in a
      randomized, double blind, cross over design. Appetite sensations were measured
      using visual analogue scales. RESULTS: Hunger and prospective food consumption
      were negatively associated with the increasing doses of nicotine, whereas satiety
      and fullness were positively associated with the increasing doses of nicotine (p
      < 0.05). Caffeine appeared to amplify the effects of nicotine on hunger and
      fullness as a caffeine x nicotine x time interaction was observed in these scores
      (p < 0.05). The 2-mg dose of nicotine in combination with the 100-mg dose of
      caffeine caused nausea in four of the non-smokers. However, the effects of
      nicotine and the caffeine x nicotine x time interaction persisted after the
      exclusion of these subjects. CONCLUSION: Caffeine added to nicotine chewing gum
      appears to amplify its attenuating effects on appetite and the combinations of 1
      mg of nicotine with caffeine seem to be well tolerated.

PMID- 15955119
TI  - NADPH oxidase inhibitor, apocynin, restores the impaired endothelial-dependent
      and -independent responses and scavenges superoxide anion in rats with type 2
      diabetes complicated by NO dysfunction.
AB  - OBJECTIVE: We investigated the effect of apocynin, an NADPH oxidase inhibitor, in
      the impairment of vascular responses in Otsuka Long-Evans Tokushima Fatty (OLETF)
      rats (type 2 diabetic rat model) with or without (w/wo) N-nitro-l-arginine methyl
      ester treatment. METHODS: Male OLETF and littermate Long-Evans Tokushima Otsuka
      (LETO) (28 weeks old) rats were separated as follows: LETO w/wo apocynin (Gp C,
      Gp C-apo), OLETF w/wo apocynin (Gp DM, Gp DM-apo) and OLETF plus l-nitro arginine
      acetate ester w/wo apocynin (Gp DMLN, Gp DMLN-apo). Five days after, peritoneal
      macrophages were stimulated with thioglycolate. Two days after, they were
      evaluated. RESULTS: Plasma glucose and lipid levels remained unchanged.
      Acetylcholine-induced nitric oxide-dependent (NO-dependent) relaxation and
      nitroglycerin-induced NO-independent relaxation were improved in the Gp DMLN-apo,
      compared with that in Gp DMLN. Tone-related basal NO release and plasma NO(2) (-)
      and NO(3) (-) tended to be lower in Gp DM and Gp DMLN groups. The increased
      amount of superoxide anion released from macrophages in Gp DM and Gp DMLN was
      restored by apocynin. Intimal thickening was observed in aortae of Gp DM and Gp
      DMLN animals; however, there was little in aortae of Gp DM-apo and Gp DMLN(-) apo
      rats. Increased tumour necrosis factor-alpha (TNF-alpha) in the Gp DM and Gp DMLN
      was also restored by apocynin treatment. CONCLUSION: Apocynin restores the
      impairment of endothelial and non-endothelial function in diabetic angiopathy in
      OLETF without changing plasma glucose and lipid levels. NO and O(2) (-) may play
      a role in this process by decreasing TNF-alpha levels.

PMID- 15955120
TI  - Electrical muscle stimulation acutely mimics exercise in neurologically intact
      individuals but has limited clinical benefits in patients with type 2 diabetes.
AB  - BACKGROUND: Electrical muscle stimulation mimics exercise in individuals with
      neurological injury or disease and improves measures of fitness and glucose
      metabolism. Physical activity improves features of the metabolic syndrome in
      patients with type 2 diabetes but many patients find it difficult to exercise.
      AIMS: To determine whether use of an electrical muscle stimulator mimics exercise
      in neurologically intact individuals and has metabolic benefits in patients with
      type 2 diabetes. METHODS: Acute changes in pulse, blood pressure and energy
      expenditure were measured in 33 healthy volunteers using the muscle stimulator.
      Acute changes in glucose uptake were measured in five subjects with type 2
      diabetes. Body composition, features of the metabolic syndrome and measures of
      insulin sensitivity were measured before and after 12 weeks daily use of the
      stimulator in four subjects with type 2 diabetes. RESULTS: The muscle stimulator
      acutely increased pulse, blood pressure, energy expenditure and glucose uptake.
      Daily use over 12 weeks improved insulin stimulated nonesterified fatty acid
      suppression but did not result in changes in body composition or clinical
      parameters. CONCLUSION: Although the muscle stimulator acutely mimics exercise,
      limitations in the size of the stimulating current mean that the magnitude of
      these changes is too small to produce clinical benefit.

PMID- 15955121
TI  - Analysis of criteria for metabolic syndrome in a population-based study of
      Japanese-Brazilians.
AB  - OBJECTIVE: Criteria for metabolic syndrome (MS) differ particularly regarding the
      definition of central obesity and consequently, there could be differences in the
      assessment of cardiovascular risk. We estimated the prevalence of metabolic
      syndrome, compared the agreement of the World Health Organization (WHO) criteria
      with the standard and a modified National Cholesterol Education Program (NCEP)
      criterion and investigated whether additional factors were associated with the
      diagnosis of the syndrome in a Japanese descendant population. METHODS: In this
      cross-sectional, population-based survey, 1166 Japanese-Brazilians (533 men, 633
      women) aged 57.4 +/- 12.4 years with mean body mass index (BMI) and waist of 25.2
      +/- 4.0 kg/m(2) and 84.5 +/- 10.6 cm, respectively, were included. McNemar and
      kappa statistics were used to assess the concordance between WHO criteria with
      the standard and a modified NCEP criteria (waist of 90 and 80 cm, for men and
      women, respectively). In logistic regression analysis, a number of metabolic
      variables and albumin-to-creatinine ratio were included to test independent
      associations with metabolic syndrome defined by the modified NCEP criteria.
      RESULTS: According to WHO, 55.4% (95% CI 52.5-58.2%) of the subjects had MS and
      to NCEP 47.4% (95% CI 44.6-50.0%). WHO criterion detected 48.3% of central obese
      subjects while NCEP only 14.0%. Kappa statistics showed a good strength of
      agreement (k = 0.67, p < 0.01) between WHO and NCEP standard definitions of MS.
      Using the modified NCEP criterion for Asians, more subjects with metabolic
      syndrome were identified (58%) and agreement with WHO was improved (k = 0.72, p <
      0.001). However, similar Framingham risk scores were attributed to the subsets of
      subjects classified by any of the three criteria. Areas under the receiver
      operating characteristic curves, obtained for the modified waist values to
      diagnose metabolic syndrome according to WHO, were > 0.80 and corresponded,
      respectively, to sensitivity and specificity of 63 and 83% for men and 77 and 72%
      for women. In final logistic regression model, age, male sex, BMI and homeostasis
      model assessment-insulin resistance but not with albumin-to-creatinine ratio
      (ACR) were independently associated with the syndrome. CONCLUSIONS: High
      prevalence of MS, independent of the criterion considered, was found in this
      Japanese-Brazilian population. The replacement of waist cutoff by those proposed
      by WHO for Asians lead to this diagnosis in a higher number of subjects with
      elevated cardiovascular risk. Our data did not support that ACR should be
      included in the classical definition of MS in Japanese descendants as previously
      suggested by WHO.

PMID- 15955122
TI  - Topiramate ameliorates hyperglycaemia and improves glucose-stimulated insulin
      release in ZDF rats and db/db mice.
AB  - Topiramate (TPM) is a novel neurotherapeutic agent. Clinical studies reported
      that TPM treatment reduced body weight and decreased fasting blood glucose levels
      in obese patients with or without type 2 diabetes. It is unclear whether the
      blood glucose-normalizing phenomenon observed during TPM treatment is a primary
      effect or the consequence of reduced food intake and weight loss. In the present
      studies, we chronically treated female Zucker diabetic fatty (ZDF) rats (fed with
      a diabetogenic diet) and db/db mice with TPM (30-300 mg/kg/day) to examine the
      effect of TPM on hyperglycaemia and its relationship with food intake and body
      weight gain. Our data showed that TPM treatment markedly reduced blood glucose
      levels in both ZDF rats and db/db mice without a significant reduction in body
      weight gain. Pair-fed db/db mice treated with the vehicle alone did not exhibit a
      significant decrease in blood glucose levels compared with mice fed ad libitum.
      TPM treatment increased glucose-stimulated insulin release by 2-3-fold during an
      oral glucose tolerance test in both ZDF rats and db/db mice. We also observed a
      1.4-fold increase of pancreatic insulin content and heightened insulin
      immunostaining in pancreatic beta cells in db/db mice treated with TPM. Our data
      suggest that the antidiabetic effect of TPM is independent of the changes in body
      weight gain and food intake. Improved glucose-induced insulin release may, in
      part, underlie the mechanisms by which TPM ameliorates the hyperglycaemia.

PMID- 15955123
TI  - Abdominal diameter index: a more powerful anthropometric measure for prevalent
      coronary heart disease risk in adult males.
AB  - AIM: The authors wished to compare the strength of association of several
      anthropometric measures of body size and fat distribution among themselves and in
      comparison with other known risk factors for prevalent coronary heart disease
      (CHD). METHODS: Prevalent CHD was assessed in 466 middle-aged, male, multiracial
      Triborough Bridge and Tunnel Authority officers in New York City by verified
      history, electrocardiogram or exercise stress test. Anthropometric measures
      included body mass index, waist, hip and thigh circumferences, waist-hip ratio,
      waist-thigh ratio, sagittal abdominal diameter and abdominal diameter index
      (sagittal abdominal diameter/thigh circumference). Results were compared with
      other CHD risk factors measured simultaneously (history of diabetes, smoking,
      blood pressure, lipid profile, apolipoproteins A and B, lipoprotein (a),
      homocysteine, fibrinogen, urinary microalbumin, serum vitamin E and ferritin) and
      a calculated 10-year CHD risk using a Framingham algorithm (10-year Framingham
      CHD risk). RESULTS: CHD was found in 29 individuals. Of the six anthropometric
      measures, abdominal diameter index gave the largest and most significant
      standardized odds ratio (OR) for CHD [1.80, 95% confidence interval (CI) 1.20,
      2.71], equivalent to 10-year Framingham CHD risk. Men in the highest compared
      with the lowest tertile of abdominal diameter index had a univariate OR of 5.47
      (95% CI 1.55, 19.28) which was the only anthropometric measure that remained
      significant after adjusting for 10-year Framingham CHD risk. CONCLUSIONS: For
      middle-aged American men, abdominal diameter index may be the most powerful
      anthropometric measure of risk for prevalent CHD.

PMID- 15955124
TI  - The effect of metformin and rosiglitazone on postprandial lipid metabolism in
      obese insulin-resistant subjects.
AB  - INTRODUCTION: Obese insulin-resistant individuals exhibit a dyslipidaemia due to
      raised levels of both hepatically and intestinally derived lipoproteins. However,
      little is known about the related dysregulation of intestinally derived
      lipoproteins. We examined whether the insulin-sensitizing agents, metformin and
      rosiglitazone, improve intestinal lipoprotein metabolism in obese insulin
      resistant individuals. METHODS: Thirty male obese (body mass index > 26; waist
      circumference > 100 cm) insulin-resistant [homeostasis model assessment (HOMA)
      score > 2.0] subjects were randomized to either a metformin (1 g bd),
      rosiglitazone (4 mg bd) or control treatment group for a period of 8 weeks.
      Fasting and postprandial lipid metabolism was studied before and after the
      intervention period. RESULTS: Metformin and rosiglitazone both significantly
      improved insulin sensitivity, but this was not paralleled by improvement in
      dyslipidaemia. With rosiglitazone relative to control there was a significant (p
      < 0.05) increase in the area under the apolipoprotein (apo) B48 curve following
      the oral fat load and a decrease in the ratio of triglyceride to apo B48 levels
      postprandially following rosiglitazone treatment. CONCLUSION: In obese insulin
      resistant subjects metformin and rosiglitazone both improve insulin sensitivity,
      as measured by HOMA, without improvement in lipid metabolism. Rosiglitazone may
      have a detrimental effect on chylomicron metabolism by an increase in
      postprandial apo B48 levels, and this requires further investigation.

PMID- 15955125
TI  - Coronary arterial calcification is associated with albuminuria in type 2 diabetic
      patient.
AB  - AIM: Although microalbuminuria has been suggested as an independent risk factor
      for ischemic heart disease, the relationship between diabetic nephropathy and
      macroangiopathy remains unclear. Previously, we reported that coronary artery
      calcification detected by electron beam computed tomography (EBCT) could indicate
      the degree of coronary atherosclerosis in type 2 diabetic patients. In this
      study, we examine the association between coronary arterial calcification and
      microalbuminuria and aortic calcification and microalbuminuria. METHODS: Two
      hundred and fifty-six patients, including 177 type 2 diabetic patients (106
      patients with normoalbuminuria, 71 with microalbuminuria) and 79 non-diabetic
      patients were evaluated by assessing the urinary albumin excretion rate and using
      EBCT to determine a coronary calcification score (CCS) and an aortic
      calcification score (ACS). RESULTS: No differences were observed regarding age,
      smoking index or BMI. Diabetic patients exhibited a greater CCS than non-diabetic
      subjects (non-diabetes 33 +/- 75 vs. diabetes 203 +/- 467, p < 0.05). Diabetic
      patients with microalbuminuria exhibited the most advanced CCS (253 +/- 491, p <
      0.05). In contrast, no difference was observed in ACS among three groups.
      Multiple regression analysis showed that CCS is significantly associated with
      urinary albumin excretion rate as well as age, duration of diabetes and serum
      creatinine (R(2) = 0.31), while ACS is strongly associated with age, smoking,
      serum creatinine, systolic blood pressure and low-density lipoprotein cholesterol
      level (R(2) = 0.29). CONCLUSION: Increased urinary albumin excretion is
      associated with coronary arterial calcification in diabetic patients.

PMID- 15955126
TI  - The prevalence of the metabolic syndrome in Greece: the MetS-Greece Multicentre
      Study.
AB  - BACKGROUND: The Third Report (ATP III) of the National Cholesterol Education
      Program Expert Panel (NCEP) highlighted the importance of identifying and
      treating patients with the metabolic syndrome (MetS) to prevent cardiovascular
      disease (CVD) and progression to diabetes mellitus. Limited information is
      available about the prevalence of MetS, as defined by the NCEP ATP III, in
      Europe, especially in Greece. OBJECTIVE: To estimate the prevalence of the MetS
      in Greece, The MetS-Greece Study. DESIGN AND PARTICIPANTS: A cross-sectional
      analysis of a representative sample of Greek adults (4153 participants older than
      18 years). One group consisting of military personnel (n = 300) and another one
      from a Greek Muslim Community (n = 300) were used for comparison. In all, 4753
      subjects were included in the final analysis. RESULTS: All subjects from the
      general population were Caucasian men (49%) and women (51%), living in urban (n =
      2243, 54%), semi-urban (n = 1038, 25%) and rural (n = 872, 21%) areas. The age
      standardized prevalence of the MetS was 23.6%[95% confidence interval (CI): 22.4
      25.1%]. This was similar in men (24.2%, 95% CI: 22.3-25.2%) and women (22.8%, 95%
      CI: 21.4-25.0%) (p = 0.3). The prevalence increased with age in both sexes, 4.8%
      among participants aged 19-29 years and 43% for participants over 70 years old (p
      for trend < 0.0001). There was a 14.7-fold increase in odds ratio for having MetS
      in the age group > 70 years old compared with that of 19-29 years old (p <
      0.0001) Most of those with MetS had three components of the syndrome (61%), 29%
      had four and 10% had all five components. Abdominal obesity (82%) and arterial
      hypertension (78%) were the most common abnormalities in both sexes. The Greek
      Muslim Community, on a high-saturated fat diet, had the highest prevalence of the
      MetS (35.2%, 95% CI: 30.4-40.3%), and the military group, with a high physical
      activity level and a diet 'close' to Mediterranean, had the lowest (9.4%, 95% CI:
      6.2-13.1%). According to the 2001 Census, about 2.3 million Greeks may have the
      MetS. CONCLUSIONS: These results show that the MetS is highly prevalent in the
      Greek adult population. This may have major implications for the incidence of
      CVD. Promoting healthy diets, low caloric intake and physical activity must be
      urgently undertaken.

PMID- 15955127
TI  - Association of adiponectin and resistin with adipose tissue compartments, insulin
      resistance and dyslipidaemia.
AB  - AIM: In this study, we investigated the association of plasma adiponectin and
      resistin concentrations with adipose tissue compartments in 41 free-living men
      with a wide range of body mass index (22-35 kg/m(2)). METHODS: Using enzyme
      immunoassays, plasma adiponectin and resistin were measured. Intraperitoneal,
      retroperitoneal, subcutaneous abdominal and posterior subcutaneous abdominal
      adipose tissue masses (IPATM, RPATM, SAATM and PSAATM, respectively) were
      determined using magnetic resonance imaging. Total adipose tissue mass (TATM) was
      measured using bioelectrical impedance. Insulin resistance was estimated with the
      help of homeostasis model assessment (HOMA) score. RESULTS: In univariate
      regression, plasma adiponectin levels were inversely related to IPATM (r = 
      0.389, p < 0.05), SAATM (r = -0.500, p < 0.001), PSAATM (r = -0.502, p < 0.001),
      anterior SAATM (r = -0.422, p < 0.01) and TATM (r = -0.421, p < 0.01). In
      multiple regression models, adiponectin was chiefly correlated with PSAATM.
      Plasma adiponectin concentrations were also inversely correlated with HOMA score
      (r = -0.540, p < 0.001) and triglyceride (r = -0.632, p < 0.001), and positively
      correlated with high-density lipoprotein cholesterol (r = 0.508, p < 0.001).
      There were no significant correlations between resistin levels and adipose tissue
      masses, insulin resistance or dyslipidaemia. CONCLUSIONS: In men, total body fat
      is significantly correlated with plasma adiponectin, but not with plasma resistin
      levels. Low plasma adiponectin levels appear to be chiefly determined by the
      accumulation of posterior subcutaneous abdominal fat mass, as opposed to intra
      abdominal fat, and are strongly predictive of insulin resistance and
      dyslipidaemia.

PMID- 15955128
TI  - Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic
      patterns induced in the normal rat by feeding an adequate diet containing
      fructose as sole carbohydrate.
AB  - Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor
      to the development of glucose intolerance, dyslipidaemia and hypertension in non
      insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle,
      consumption of energy-rich diet, obesity, longer lifespan, etc., are important
      reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous
      extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS)
      and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert
      hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical
      setting. As no work has been carried out so far to assess the effect of PM, OS
      and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and
      hypertriglyceridaemia, we undertook this study to assess whether these extracts
      attenuate the metabolic alteration induced by fructose-rich diet in rats. Five
      groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose
      diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200
      mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days.
      Fructose feeding to normal rats for 30 days significantly increased serum
      glucose, insulin and triglyceride levels in comparison with control. Treatment
      with all the three plants extract for 30 days significantly lowered the serum
      glucose levels in comparison with control group. However, only PM extract
      substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and
      FG had no significant effect on these parameters. Results of this study, in
      addition to previous clinical benefits of PM seen in NIDDM subjects, are
      suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the
      associated disorder of type 2 diabetes; however, OS and FG may not be useful.
      Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and
      pterostilbene) have been identified in the PM, yet future studies are required to
      certify their efficacy and safety before clinical scenario.

PMID- 15955129
TI  - Inverse association between plasma homocysteine, sulphonylurea exposure and
      physical activity: a community-based sample of type 2 diabetes patients in the
      Skaraborg hypertension and diabetes project.
AB  - AIM: This study aimed to investigate levels of Homocysteine (tHcy) and folate in
      a population-based sample of patients with type 2 diabetes. In particular, the
      study explored modifiable determinants such as treatment for diabetes, life
      style, glucose control and kidney function. PATIENTS AND METHODS: In a community
      based surveillance of patients with type 2 diabetes, 196 men and 191 women were
      consecutively identified in primary care and characterized by cardiovascular
      disease (CVD) risk factors focusing on components in the metabolic syndrome. For
      categorical associations plasma tHcy was dichotomized using the upper 10
      percentiles of the distribution. RESULTS: Treatment with sulphonylurea was
      associated with lower serum levels of tHcy compared to those on diet alone. The
      association was confined to women [odds ratio 0.14; confidence interval 0.03-0.8]
      and remained significant when differences in factors related to the metabolic
      syndrome, life style and previous CVD were accounted for, but was lost when
      adjusted for HbA1c. There was an inverse dose-related association between
      physical activity and plasma levels of tHcy (men p = 0.006, women p = 0.034), and
      a positive association with serum levels of creatinine (men p = 0.004, women p <
      0.001). CONCLUSIONS: The association with physical activity might be one
      contributing explanation for its well-known protective effect on cardiovascular
      disease. The over risk for vascular complications in diabetic patients with
      kidney disease may be partially explained by high levels of tHcy and should be
      further explored. Prospective studies are particularly needed on various
      treatment for type 2 diabetes and tHcy to explore possible implications for
      clinical procedures and for public health.

PMID- 15955130
TI  - Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in
      achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic
      patients with or without the metabolic syndrome in the MERCURY I trial.
AB  - AIM: The metabolic syndrome (MS) increases the risk of coronary heart disease,
      yet few data are available on the effects of statin treatment in improving lipid
      measures in patients with the syndrome. This analysis compares the effects of
      statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal
      achievement and lipid levels in hypercholesterolaemic patients with or without
      the MS. METHODS: The Measuring Effective Reductions in Cholesterol Using
      Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with
      atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8
      weeks in patients with coronary or other atherosclerotic diseases or diabetes who
      had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l.
      Modified National Cholesterol Education Program Adult Treatment Panel III (ATP
      III) criteria for the MS were met by 1342 (43%) of 3140 patients. RESULTS: LDL-C
      goal achievement rates and reductions in LDL-C, total cholesterol and non-high
      density lipoprotein cholesterol (HDL-C) were similar in patients with and without
      the MS within statin treatment groups; triglycerides were reduced more and HDL-C
      tended to be increased more in patients with the MS, as expected. Treatment with
      rosuvastatin 10 mg was more effective in allowing patients with and without the
      MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg,
      simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons);
      consistently produced greater reductions in LDL-C, total cholesterol and non-HDL
      C, compared to these treatments; and produced similar or greater reductions in
      triglycerides and increases in HDL-C, compared to the other treatments.
      CONCLUSIONS: Statin therapy is effective in allowing LDL-C goal achievement and
      improving the lipid profile in hypercholesterolaemic high-risk patients with the
      MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and
      lipid lowering over other statins at commonly used doses in patients both with
      and without the MS.

PMID- 15955131
TI  - Predictors of programme adherence and weight loss in women in an obesity
      programme using meal replacements.
AB  - OBJECTIVE: To explore predictors of programme adherence and weight loss in
      patients participating in a weight management programme using meal replacements
      (MR). DESIGN: One hundred and fifty healthy obese women, age 48.5 years (s.d. =
      8.3); weight, 97.6 kg (13.4); body mass index (BMI) 36.5 (3.7), participated in a
      longitudinal study with a 16-week acute weight loss phase (Phase 1) followed by 1
      year of a trial of weight-loss maintenance (Phase 2). Energy intake during Phase
      1 totaled 900 kcal (3.7 MJ) a day from a diet including two MR. Energy intake
      during Phase 2 consisted of either MR or a low-fat diet with a calculated energy
      deficit of 600 kcal/day (2.5 MJ). METHODS: Weight, height and waist circumference
      were measured and body composition assessed by air plethysmography (Bodpod).
      Glucose and insulin were measured by standard immunoassays and insulin
      sensitivity assessed by homeostatic model assessment. RESULTS: At the end of 16
      weeks, 114 subjects (76%) completed Phase 1 and achieved a mean weight loss of
      8.95 kg (3.38). Adherence to Phase 1 was predicted by weight loss over the first
      2 weeks (p < 0.001). Weight loss during Phase 1 was predicted by initial weight
      and initial systolic blood pressure. Adherence to Phase 2 was not predicted by
      physiological measures. Weight loss maintenance in Phase 2 (not gaining more than
      3% of the weight at start of phase 2) was predicted by cholesterol and
      triglyceride measured at the start of Phase 2 but otherwise was not predicted by
      the physiological measures. Initial insulin sensitivity did not predict weight
      loss in either phase. CONCLUSION: Participants whose weight loss over the first 2
      weeks falls in the bottom third may need additional intervention if they are to
      continue in this type of programme. A battery of physiological measures at entry
      to a MR weight loss and maintenance programme explains only a very small
      proportion of the variation in weight loss.

PMID- 15955132
TI  - High-fat diet enhances visceral advanced glycation end products, nuclear O-Glc
      Nac modification, p38 mitogen-activated protein kinase activation and apoptosis.
AB  - High-fat diet intake often leads to obesity, insulin resistance and hypertension,
      which present a common and detrimental health problem. However, precise mechanism
      underlying tissue damage due to high-fat diet-induced obesity has not been
      carefully elucidated. The present study was designed to examine the effect of
      high-fat diet intake on visceral advanced glycation end products (AGEs)
      formation, nuclear O-Glc-NAc modification and apoptosis in heart, liver and
      kidney. Adult male Sprague-Dawley weight-matched rats were fed for 12 weeks with
      a high-fat diet (45% kcal from fat) or an isocaloric low-fat diet (10% kcal from
      fat). High-fat diet feeding significantly elevated body weight. Blood pressure
      and heart rate were comparable between the two rat groups. Competitive enzyme
      linked immunosorbent assay showed significantly elevated serum AGE levels,
      visceral AGE formation, caspase-3 activation and cytoplasmic DNA fragmentation in
      heart and liver but not kidney samples of high-fat diet fed rats compared with
      those from low-fat diet fed group. Western blot analysis further revealed that
      high-fat diet feeding induced overt nuclear O-Glc-NAc modification and p38
      mitogen-activated protein kinase activation in heart and liver although not in
      kidney samples of the high-fat diet-fed rats. Collectively, our results indicated
      that high-fat diet intake is associated with obesity accompanied by elevated
      serum and visceral AGEs, visceral post-translational nuclear O-Glc-NAcylated
      modification and apoptosis, which may contribute to high-fat diet-induced tissue
      damage.

PMID- 15955133
TI  - No association of the 94T/G polymorphism in the adiponectin gene with diabetic
      complications.
AB  - AIM: This study examined a possible association of the T/G polymorphism at
      nucleotide 94 in the adiponectin gene with the prevalence of diabetic
      complications. METHODS: The study was performed in 696 patients with type 1
      diabetes and type 2 diabetes. Genotyping was performed by means of polymerase
      chain reaction and subsequent cleavage by using SmaI restriction endonuclease.
      RESULTS: The 94G/G genotype was significantly more prevalent in patients with
      type 2 diabetes (2.2%) than in type 1 diabetics (0.0%) (p = 0.02), whereas no
      differences were found for frequencies of the 94T/T and the 94G/T genotypes,
      respectively. In patients with type 1 diabetes, 45 of 239 patients were
      heterozygous for the 94T/G polymorphism (carrier rate (CR): 18.8%; allele
      frequency (AF): 0.094). In type 2 diabetics, 71 of 457 patients were heterozygous
      and 10 patients were homozygous for the 94G/G genotype (CR: 17.7%; AF: 0.10). No
      association with diabetic nephropathy, diabetic neuropathy or diabetic
      retinopathy was found for either genotype in patients with type 1 and type 2
      diabetes. CONCLUSIONS: The 94T/G polymorphism in the adiponectin gene is not
      associated with diabetic complications. The significance of a higher prevalence
      of the G allele in type 2, compared to type 1 diabetes remains to be clarified.

PMID- 15955137
TI  - Advances in the diagnosis, evaluation, and management of malignant pleural
      mesothelioma.
AB  - Malignant mesothelioma is an insidious neoplasm arising from the mesothelial
      surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica
      vaginalis. A total of 80% of all cases are pleural in origin. The predominant
      cause of malignant mesothelioma is inhalational exposure to asbestos, although
      evidence is increasing to support the hypothesis that simian virus-40 virus plays
      a role in cocarcinogenesis. Immunohistochemical markers such as calretinin, WT-1,
      and cytokeratin 5/6 are becoming established diagnostic markers. Preliminary data
      suggests that a soluble form of mesothelin could serve as a serum marker for
      established and early cases of mesothelioma. Positron emission tomography with 18
      fluorodeoxyglucose in conjunction with computed tomograhy scanning has improved
      preoperative imaging and staging. Prognostic factors have been identified and
      verified. Negative indicators include thrombocytosis, high leukocyte counts, poor
      performance status, and nonepithelial histology. For the first time, there is now
      evidence that some treatments are increasing the quality and quantity of life for
      patients with mesothelioma. Chemotherapy, with the new multi-targeted antifolate
      drug Pemetrexed, combined with cisplatin, has shown superior survival rates in a
      large phase III trial when compared to cisplatin alone. High-dose intensity
      modulated radiotherapy when administered after extrapleural pneumonectomy has
      resulted in excellent local control. Multimodality treatment programs that
      combine surgical cytoreduction with novel forms of radiation therapy and more
      effective chemotherapy combinations may offer significant increases in survival
      for certain subgroups of mesothelioma patients. Innovative palliative approaches
      have proved successful in alleviation of the significant symptoms experienced by
      many mesothelioma patients. Experimental treatments such as immunotherapy and
      gene therapy present a window of hope for all mesothelioma patients, and in the
      future, may be combined with 'standard therapy' in multimodality protocols.
      Patients with adequate performance status should be enrolled into clinical trials
      where possible. Over the past decade, significant advances have been made on
      several fronts that have improved the ability to diagnose a stage, define
      prognosis, and treat malignant pleural mesothelioma.

PMID- 15955138
TI  - Treatment of idiopathic pulmonary fibrosis: is there anything new?
AB  - Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing
      interstitial pneumonia of unknown aetiology and is associated with the
      histological picture of usual interstitial pneumonia. Treatment in most cases is
      unsatisfactory and the prognosis remains poor. There is insufficient evidence to
      suggest that any treatment, apart from lung transplantation, improves survival or
      halts disease progression for IPF patients. Data on treatment response are
      limited by the paucity of clinical trails, the lack of homogenous clinical
      features, the small number of patients, and the absence of histological and
      radiological documentation in many cases. Anti-inflammatory medications such as
      corticosteroids, azathioprine and cyclophosphamide remain the commonly used
      medications. More recently, it has been proposed that IPF is a primary fibrotic
      disease rather than an inflammatory condition. Antifibrotic agents such as
      colchicine, pirfenidone and interferon-gamma (IFN-gamma) have been tried.
      However, a recent placebo-controlled trial has failed to demonstrate a
      significant effect of IFN-gamma on disease progression, lung function or quality
      of life in IPF patients, though a clinically significant survival benefit of the
      drug could not be ruled out.

PMID- 15955139
TI  - Levels of tumour necrosis factor-alpha and IL-1alpha in newly diagnosed and
      multidrug resistant tuberculosis.
AB  - BACKGROUND: The pro-inflammatory cytokines tumour necrosis factor (TNF)-alpha and
      IL-1alpha play key roles in host defence against tuberculosis (TB) but there is
      little knowledge of their levels in multidrug resistant TB (MDR-TB). The aim of
      the present study was to investigate the levels of TNF-alpha and IL-1alpha and
      their relationship with the levels of T helper (CD4+), T suppressor (CD8+) and
      total lymphocytes (CD45+) in newly diagnosed TB (N-TB) and MDR-TB. METHODOLOGY:
      This study assessed 19 N-TB patients (M/F : 17/2) and 11 MDR-TB patients (M/F :
      10/1). Serum TNF-alpha and IL-1alpha were assessed by ELISA. Lymphocyte
      expression of CD45, CD4, CD8, CD3, CD23, CD19 and CD95 were determined by flow
      cytometry. RESULTS: The levels of TNF-alpha, IL-1alpha, and CD4, CD4/CD8, CD45,
      CD19, CD23 and CD95 positive lymphocytes were lower in MDR-TB than in N-TB
      patients (P < 0.05). Statistically, there was a positive correlation between TNF
      alpha and IL-1alpha (r = 0.92) for both MDR-TB and N-TB. For both groups, both
      TNF-alpha and IL-1alpha correlated with CD4+ lymphocytes (r = 0.48). TNF-alpha
      and IL-1alpha showed negative correlations with CD8+ lymphocytes (r = -0.81, r = 
      0.73) (P < 0.01) in MDR-TB patients. CONCLUSION: The lower levels of cytokines
      and numbers of T helper lymphocytes in MDR-TB compared with N-TB implies that the
      immune profiles of the two groups are different, and may be important in the
      natural history of the disease.

PMID- 15955140
TI  - Serum IL-18 levels in tuberculosis: comparison with pneumonia, lung cancer and
      healthy controls.
AB  - OBJECTIVE: The aim of the present study was to document the serum IL-18 levels in
      patients with pulmonary tuberculosis (P-TB), extrapulmonary tuberculosis (EP-TB),
      pneumonia, lung cancer and in healthy controls, and to investigate whether it may
      assist in the differential diagnosis of P-TB. METHODOLOGY: A total of 116
      patients were included in the study. The study population consisted of patients
      with P-TB, EP-TB, pneumonia and lung cancer and controls. P-TB patients were
      graded according to sputum positivity and extent of disease. Serum levels of IL
      18 (ELISA) were compared between groups and with other clinical measures of
      disease. RESULTS: Compared with the controls, all groups of patients had
      increased serum levels of IL-18. The highest mean concentration of IL-18 was
      observed in P-TB. Serum levels of IL-18 in the patients with P-TB correlated well
      with the extent of disease. CONCLUSIONS: Although increased serum levels of IL-18
      were not specific for TB, the increased levels may favour active TB in
      radiologically advanced disease where CXR findings are difficult to interpret,
      and sputum smears or cultures are not helpful.

PMID- 15955141
TI  - Clinical usefulness of serum pyridinoline cross-linked carboxyterminal
      telopeptide of type I collagen for diagnosis of bone metastases in patients with
      primary lung cancer.
AB  - OBJECTIVE: Recently, various blood and urine markers of bone metabolism have been
      developed and applied to the diagnosis of bone metastases. However, the cut-off
      values for each parameter have not yet been completely defined. In this study,
      the usefulness of serum pyridinoline cross-linked carboxyterminal telopeptide of
      type I collagen (I CTP) was assessed for detecting bone metastases from primary
      lung cancer and the most efficient cut-off value for I CTP based on the receiver
      operating characteristic curve was calculated. METHODOLOGY: Over a 1-year period,
      serum I CTP and serum alkaline phosphatase (ALP) were assayed for 87 primary lung
      cancer patients, including 21 bone metastases-positive cases at Nagoya Ekisaikai
      Hospital, Nagoya, Japan. RESULTS: I CTP was significantly higher in patients with
      bone metastases than in the group without bone metastases. In contrast, there was
      no significant difference in serum ALP between the two groups. The most efficient
      cut-off value for I CTP computed in this study was 6.4 ng/mL. This was higher
      than the recommended value (4.5 ng/mL) based on the data from the summated values
      obtained for lung cancer, breast cancer and prostate cancer, as well as the
      maximum value for healthy controls (4.9 ng/mL). CONCLUSION: These results suggest
      that measurement of serum I CTP is a useful test for diagnosing bone metastases
      from lung cancer. Each type of cancer has a different pattern of bone turnover at
      the site of bone metastases. Considering that lung cancer mainly metastasizes to
      bone in an osteolytic pattern, it is proposed to set a higher cut-off value for
      lung cancer patients than the currently recommended value.

PMID- 15955142
TI  - Antioxidant enzyme activities in healthy Chinese adults: influence of age, gender
      and smoking.
AB  - OBJECTIVE: Specific antioxidant enzymes play a vital role in regulating and
      maintaining oxidant species. The aim of this study was to determine these
      antioxidant enzyme activities (i.e. catalase (CAT), superoxide dismutase (SOD)
      and glutathione peroxidase (GPx)) in erythrocytes from a group of healthy Chinese
      subjects and to study the influence of age, gender and smoking habits on the
      enzyme activities. METHODOLOGY: Chinese healthy subjects (n = 276) were grouped
      according to their age range, gender differences and smoking habits. Antioxidant
      enzyme activities were measured spectrophotometrically using standard kinetic
      methods. RESULTS: There was a significant decrease in erythrocyte GPx activity in
      ever-smokers compared with non-smokers (47.10 +/- 1.33 mU/g haemoglobin (Hb) vs.
      51.41 +/- 1.64 mU/g Hb, P < 0.05). Age-related significant increases in
      erythrocyte CAT and SOD activities were found in non-smokers but not in ever
      smokers. There was no age-related difference in erythrocyte GPx activity in
      either non-smokers or ever-smokers. Among those >60 years old, erythrocyte CAT
      and GPx activities were significantly lower in ever-smokers than in non-smokers
      (29.70 +/- 3.07 mU/g Hb vs. 41.63 +/- 4.92 mU/g Hb (P < 0.05), and 47.55 +/- 2.00
      mU/g Hb vs. 55.30 +/- 3.60 mU/g Hb (P < 0.05), respectively). It was also found
      that females had higher erythrocyte GPx activity than males but this difference
      did not reach significance in non-smokers. CONCLUSION: From the results of this
      study, it is concluded that oxidative stress seems to be present in elderly ever
      smokers among the Chinese population.

PMID- 15955143
TI  - Predictive equations and the reliability of the impulse oscillatory system in
      Japanese adult subjects.
AB  - BACKGROUND: The impulse oscillation system (IOS) measures respiratory impedance
      (Zrs) in terms of resistance (Rrs) and reactance (Xrs) at multiples of 5 Hz.
      These measurements can be used clinically to help diagnose and monitor
      respiratory disorders, independent of effort. METHODOLOGY: The predictive
      equation for resistance at 5 and 20 Hz and impedance at 5 Hz (R5, R20, X5), for
      the first time, in 299 Japanese adult subjects was determined. In addition, the
      within single day variation and between day variation were determined. RESULTS:
      The predictive equation for R5, R20 and X5 revealed a clear difference with
      respect to the subject's smoking history (lifelong non-smoker, n = 166, adjusted
      r = 0.55, 0.46 and 0.57, respectively, vs. smoker, n = 133, adjusted r = 0.47,
      0.42 and 0.47, respectively). This difference was less obvious with respect to
      gender (female, n = 120, adjusted r = 0.42, 0.20 and 0.47, respectively, vs.
      male, n = 179, adjusted r = 0.46, 0.37 and 0.47, respectively). The predictive
      equations were dependent on the log of height (H) for both R5 and R20, and on age
      and log of height for X5. The equations were: R5 (KPa/L/s) = -3.841167 x logH +
      8.671580; R20 (KPa/L/s) = -2.546561 x logH + 5.841867; and X5 (KPa/L/s) = 
      0.000097 x Age + 1.018597 x logH - 2.343672. For these parameters there were no
      statistically significant differences for within day repeatability or between day
      variations (P > 0.05), suggesting a high degree of reproducibility for IOS
      measurements. CONCLUSION: It was possible to determine a predictive equation and
      confirm a high degree of reliability of IOS parameters in Japanese adult
      subjects.

PMID- 15955144
TI  - High resolution CT and bronchial reversibility test for diagnosing COPD.
AB  - BACKGROUND: COPD is defined by airflow limitation that is not fully reversible
      and is associated with relevant risk factors. The diagnosis requires that other
      causes of chronic airflow limitation (CAL) be excluded. We assessed the
      diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator
      reversibility to assist in making a diagnosis of COPD. METHODOLOGY: We
      investigated 516 consecutive patients whose FEV1/FVC was less than 70% after
      inhalation of bronchodilator. HRCT was performed on all subjects and a final
      diagnosis was made only after 3 months of treatment and repeated spirometry.
      RESULTS: Of 516 cases, 54.3% had COPD, 19.8% had asthma plus emphysema, and 13.2%
      had chronic asthma. The remaining 12.7% of patients with CAL had diffuse
      panbronchiolitis, bronchiectasis, bronchiolitis obliterans, or other
      miscellaneous diseases. In these minor diseases HRCT was essential in making a
      definitive diagnosis. The sensitivities of emphysema on HRCT and of absence of
      bronchodilator response for the diagnosis of COPD were 81% and 90%, respectively,
      and the specificities of the tests were 57% and 37%, respectively. In addition,
      HRCT revealed considerable heterogeneity of COPD. Emphysema was not recognized on
      HRCT in 18.6% of COPD patients. HRCT also revealed that 17.5% of COPD patients
      had other pulmonary complications including lung fibrosis compatible with usual
      interstitial pneumonia in the lung bases. CONCLUSIONS: HRCT and the bronchial
      reversibility test had reasonable sensitivities but low specificities for
      diagnosing COPD. HRCT has some additional advantages in detecting heterogeneity
      and concomitant lung diseases in COPD.

PMID- 15955145
TI  - Comparison of existing symptom-based questionnaires for identifying COPD in the
      general practice setting.
AB  - OBJECTIVE: Underdiagnosis of COPD is widespread, at least in part due to underuse
      of spirometry. Symptom-based questionnaires may be helpful as an adjunct to
      spirometry. The aim of this study was to determine which types of questions might
      aid in identifying COPD. METHODOLOGY: Questionnaires were identified by
      literature review and input from a multinational advisory board of primary care
      providers. Questions were placed into groups and evaluated with respect to their
      ability to perform in two scenarios: (i) to identify persons with COPD from a
      general population (Case-finding scenario); and (ii) to distinguish persons with
      COPD from those with asthma (Differential Diagnosis scenario). Questions were
      retrospectively validated using the Third National Health and Nutrition
      Examination Survey data. Potential predictive ability was examined in bivariate
      and multivariate frameworks. RESULTS: Four published question sets and six
      additional documents were included. There was agreement in the use of smoking and
      symptom-based questions, but important differences in the use of demographic,
      personal history and other information. Most question types had significant
      bivariate relationships with airway obstruction. In multivariate analysis, age,
      BMI, smoking status and pack-years, symptoms (cough, phlegm, dyspnoea, wheeze),
      and prior diagnosis consistent with asthma or COPD all showed significant ability
      to discriminate between persons with and without obstruction in a general
      population. CONCLUSION: Simple self-administered questionnaires can be used to
      identify persons for whom spirometric testing may be especially appropriate.
      Development of such questionnaires will require additional study, including
      prospective validation of items in an appropriate clinical setting and policy
      recommendations on the use of these tools.

PMID- 15955146
TI  - Outcomes and health-related quality of life following hospitalization for an
      acute exacerbation of COPD.
AB  - OBJECTIVE: The purpose of this study was to understand the outcomes for patients
      admitted to hospital for an acute exacerbation of COPD, and to determine the
      factors influencing quality of life and health service utilization of patients
      with COPD. METHODOLOGY: Hospital outcomes of 282 patients with moderate and
      severe COPD, for an acute exacerbation, were retrospectively evaluated. After 24
      months of follow up, health-related quality of life (QoL) and health service
      utilization (emergency room (ER) visit and readmission) in 54 patients admitted
      previously, were surveyed by questionnaires. RESULTS: Of 282 COPD patients
      admitted for an acute exacerbation, 28 patients (9.9%) died during
      hospitalization, 241 patients (85.5%) were discharged home, and only 13 patients
      (4.6%) needed long-term care facilities. Although over 50% of the patients had
      survived over 2 years after discharge, their QoL was poor. Patients who
      frequently went to the ER or were admitted, were those with poor QoL, severe
      dyspnoea and frequent exacerbation. COPD exacerbation and dyspnoea were the main
      factors influencing QoL of the patients. Age, comorbidity, QoL, FEV1, frequency
      of COPD exacerbation, long-term oxygen therapy, and family doctor were the
      factors determining the likelihood of patients visiting the ER. Frequency of COPD
      exacerbation, family doctor and living alone were the factors determining which
      patients were likely to be admitted to hospital. CONCLUSION: The outcomes and QoL
      of patients admitted for an acute exacerbation of COPD were poor. The major
      factors influencing QoL were frequency of COPD exacerbation and severity of
      dyspnoea. Improvement of social and medical networks (e.g. reducing the number of
      patients living alone and providing family doctors for patients) may reduce
      health care service utilization.

PMID- 15955147
TI  - Patterns of care for COPD by Japanese physicians.
AB  - OBJECTIVE: COPD treatment guidelines are available worldwide, yet it is not known
      how widely they are followed. This study evaluated the clinical care of COPD
      patients in Japan as compared to guideline recommendations. METHODS: A sample of
      general and specialist physicians was selected from private outpatient clinics
      and public hospitals in Japan. Physicians were provided two clinical vignettes
      (COPD and asthma) and asked to make a diagnosis. They were next asked to define
      diagnostic tests and treatment recommendations specifically for a COPD patient.
      Responses were compared to recommendations from current COPD guidelines. RESULTS:
      For the COPD unknown vignette, 6.2% of physicians diagnosed COPD while 54%
      diagnosed chronic bronchitis or emphysema. For COPD diagnosis, 81.9% of
      physicians recommended a CXR, 49.1% spirometry, and 17.7% a computed tomography
      scan. The most frequently recommended medication for a newly diagnosed COPD
      patient was theophylline (37.2%) followed by expectorants (32.1%) and inhaled
      anticholinergics (25.9%). Inhaled beta-agonists were recommended by fewer than
      20% of all physicians. CONCLUSION: Care for COPD patients by selected Japanese
      physicians diverges from published practice guidelines. COPD is an infrequently
      used diagnostic label; diagnostic evaluation is characterized by a high use of
      computed tomography scans, particularly by specialists; and bronchodilator use
      was low.

PMID- 15955148
TI  - The efficacy of incentive spirometry in patients with COPD.
AB  - OBJECTIVE: Although incentive spirometry (IS) is frequently used to prevent
      postoperative pulmonary complications, its efficacy in patients with COPD has not
      been documented. The aim of this study was to evaluate the effects of IS on
      pulmonary function tests, arterial blood gases, dyspnoea and health-related
      quality of life in patients hospitalized for COPD. METHODOLOGY: A total of 27
      consecutive patients (mean age, 68.4 +/- 7.9 years; 26 males) admitted for COPD
      exacerbations were recruited for the study. In total, 15 (IS treatment group)
      used IS for 2 months, together with medical treatment. The remaining 12 (medical
      treatment group) were given only medical treatment. Pulmonary function and blood
      gases were measured. Assessment of dyspnoea by visual analogue scale (VAS) and
      quality of life using the St. George's Respiratory Questionnaire (SGRQ) were
      performed at admission and after 2 months of treatment. RESULTS: The activity,
      impact and total scores for the SGRQ improved (all P < or = 0.0001), PaCO2 values
      decreased (P = 0.02), PaO2 and PAO2 values increased (P = 0.02 and P = 0.01,
      respectively) in the IS treatment group. However, there were no significant
      differences between the measurements made pretreatment and after 2 months of
      medical therapy in the medical treatment group, with regards to pulmonary
      function, blood gases, SGRQ scores and VAS. CONCLUSION: The use of IS appears to
      improve arterial blood gases and health-related quality of life in patients with
      COPD exacerbations, although it does not alter pulmonary function parameters.

PMID- 15955149
TI  - Prevalence and clinical features of cough variant asthma in a general internal
      medicine outpatient clinic in Japan.
AB  - OBJECTIVE: The aims of the present study were to examine the prevalence and
      clinical features of cough variant asthma (CVA) among patients with chronic and
      persistent cough at an outpatient clinic in Japan, and the efficacy of treatment
      with an inhaled corticosteroid. METHODOLOGY: This prospective study was conducted
      at a general internal medicine outpatient clinic in Japan over a 12-month period.
      CVA was diagnosed as chronic cough without wheezing or any apparent cause, that
      had persisted for more than 8 weeks, with a normal CXR and spirometry but with
      bronchial hyperresponsiveness to methacholine, and relief of cough after
      bronchodilator treatment. We also examined the effects of inhaled beclomethasone
      propionate on symptoms and differences in PEF between early morning and evening.
      RESULTS: Of 55 patients suffering from chronic cough, 23 satisfied the criteria
      for CVA. Their cough occurred more frequently at night and early in the morning.
      Early morning PEF was significantly lower than evening PEF with a mean
      variability of 11.5 +/- 4.1%. Treatment with beclomethasone propionate improved
      coughing and significantly increased early morning PEF, reducing variability to
      less than 10%. CONCLUSIONS: These findings suggest that CVA is most common among
      patients with chronic cough not due to any apparent cause. The efficacy of
      inhaled corticosteroid suggests that early intervention is effective in the
      treatment of CVA.

PMID- 15955150
TI  - Cough symptoms in children aged 5-14 years in Sydney, Australia: non-specific
      cough or unrecognized pertussis?
AB  - OBJECTIVE: The aim of this study was to estimate the community prevalence of
      coughing symptoms, consistent with surveillance definitions for pertussis, and
      doctor-diagnosed pertussis in children aged 5-14 years. METHODOLOGY: A telephone
      survey of a cross-sectional community sample of parents regarding their child's
      cough symptoms in the previous 12 months was undertaken in a representative
      Australian urban region. RESULTS: In 2020 interviews, parents reported that 22%
      of children had a cough lasting 2 weeks or longer in the preceding 12 months, and
      14% (283) had additional symptoms meeting the Centers for Disease Control (CDC)
      case definition for pertussis. A cough meeting the case definition was
      significantly more commonly reported by parents of children aged 5-9 years (17%;
      P < 0.001) but reported exposure to diagnosed pertussis in such cases was
      significantly more common in children aged 10-14 years (4.3%; odds ratio 12.8; P
      < 0.01). Parents of 90% of children meeting the CDC case definition sought
      medical advice. A diagnosis of pertussis was reported in only 1.2% of cases,
      which extrapolates to an annual incidence of doctor-diagnosed pertussis of
      347/100,000 (95% confidence interval, 140-714 per 100,000). This contrasts with
      29/100,000 notified cases in the same age group, time period and geographic area.
      CONCLUSION: Cough episodes meeting a clinical case definition for pertussis
      commonly used in surveillance are reported by a high proportion of carers of
      school-aged children in Australia. The majority of children who met the CDC and
      Australian case definitions for pertussis and sought medical attention were not
      identified as potentially having pertussis, suggesting underdiagnosis of
      pertussis. Even if less than half of this is true pertussis, the potential impact
      in terms of transmission of pertussis in the community is likely to be high. The
      reported incidence of doctor-diagnosed disease estimated from this survey was at
      least five and up to 20 times the official notification rate. More work needs to
      be done in raising awareness among medical practitioners of pertussis as a
      differential diagnosis in older children and adolescents with cough.

PMID- 15955151
TI  - Inflammatory profile in nasal secretions of infants hospitalized with acute lower
      airway tract infections.
AB  - OBJECTIVE: The aim of this study was to determine whether the regulatory immune
      response (interleukin (IL)-10 response) differed between children hospitalized
      with acute respiratory infections and wheezing. METHODOLOGY: Infants with signs
      and symptoms of acute viral respiratory infection, admitted during winter 2000 to
      Princess Margaret Hospital for Children, Perth, WA, Australia, were enrolled in
      this study. Nasopharyngeal aspirates were collected in the first 48 h of
      admission. Total cell count and differential cell counts were assessed. Samples
      were tested for the presence of respiratory viruses. The concentrations of the
      anti-inflammatory cytokine IL-10, and pro-inflammatory cytokines IL-8, interferon
      gamma, and IL-11 were determined by ELISA. RESULTS: Children with acute
      bronchiolitis (AB; n = 36), recurrent wheeze (RW; n = 17) and upper respiratory
      infection (URI; n = 18) were enrolled. Respitory syncytial virus was the most
      commonly detected virus in all groups. IL-10 concentrations were significantly
      increased in AB (median, 0.019 ng/mL) when compared to URI (median, 0.006 ng/mL)
      or to RW (median, 0.007 ng/mL; P < 0.05). Neutrophils were the predominant cells
      in the cytological analysis in all subjects. CONCLUSION: These data argue that
      host-response factors are important in determining the clinical phenotype,
      independent of the causative virus.

PMID- 15955152
TI  - Addition of macrolide in treating adult hospitalized community-acquired
      pneumonia.
AB  - OBJECTIVES: Current clinical practice guidelines, including those in south Asia,
      recommend the addition of a macrolide to a broad-spectrum antibiotic for the
      treatment of severe hospitalized community-acquired pneumonia (CAP). The aim of
      this study was to observe the influence of macrolide addition on clinical
      outcomes of hospitalized adult patients with CAP. METHODOLOGY: Over a 16-month
      period between 2002 and 2004, 141 eligible patients were prospectively recruited
      from an urban-based teaching hospital in Malaysia. RESULTS: Of the 141 patients,
      63 (44.7%) patients (age (standard deviation (SD)) 56 (20.0) years; 50.8% male)
      received a macrolide-containing antibiotic regimen, while 78 (55.3%; age (SD) 57
      (20.2) years; 52.6% male) were on a single broad-spectrum antibiotic only. In
      total, 39 (27.7%) and 102 (72.3%) patients had severe and 'non-severe' pneumonia,
      respectively. Irrespective of whether they had severe or non-severe pneumonia,
      there were no significant differences in mortality (non-severe pneumonia, 6.5%
      vs. 5.4%, P = 0.804; severe pneumonia, 17.6% vs. 18.2%, P = 0.966), need of
      ventilation (non-severe pneumonia, 8.7% vs. 3.6%, P = 0.274; severe pneumonia,
      23.5% vs. 13.6%, P = 0.425) or median length of hospital stay (non-severe
      pneumonia, 5.5 vs. 5 days, P = 0.954; severe pneumonia, 7 vs. 6 days, P = 0.401)
      between the two treatment regimens. CONCLUSION: This observational, non
      randomized study suggests that addition of a macrolide may not convey any extra
      clinical benefits in adult hospitalized patients with CAP.

PMID- 15955153
TI  - Factors related to recurrence of spontaneous pneumothorax.
AB  - OBJECTIVES: The purpose of this retrospective study was to identify factors
      associated with recurrent spontaneous pneumothorax (SP) in southern China, and to
      compare the therapeutic effectiveness of different procedures. METHODS: A total
      of 182 consecutive patients (89.0% male; mean age, 38.9 years), admitted with
      their first episode of pneumothorax, were reviewed retrospectively. Follow up was
      available in 138 patients (75.8%), including 68 treated by chemical pleurodesis
      and 70 by chest tube drainage alone. The cumulative recurrence rates with
      different therapeutic procedures and different chemical sclerosing agents were
      compared, and the factors that influenced the recurrence rate were analysed using
      Cox's proportional hazard model. RESULTS: The most common pre-existing lung
      disease responsible for pneumothorax was COPD (69.7%), followed by tuberculosis
      (16.5%). Recurrence was significantly more common in taller patients, patients
      with lower weight, and patients with secondary spontaneous pneumothorax. The
      cumulative recurrence rates in the pleurodesis therapy group after 6 months, 1
      and 3 years were 13, 16 and 27%, respectively, whereas in the chest tube drainage
      group the recurrence rates were 26, 33 and 50%, respectively (P < 0.05). There
      was no significant difference in the recurrence rate for those receiving
      tetracycline compared with those who received gentamicin. CONCLUSIONS:
      Spontaneous pneumothorax patients who are taller, weigh less or have secondary
      spontaneous pneumothorax are more likely to have recurrences. The risk of
      recurrence is reduced in patients who undergo chemical pleurodesis. Since there
      was no significant difference between intrapleural tetracycline and gentamicin,
      gentamicin should be considered as a potential chemical sclerosing agent.

PMID- 15955154
TI  - Successful withdrawal of inhaled corticosteroids in childhood asthma.
AB  - OBJECTIVE: Although inhaled corticosteroids are useful and effective in the
      prophylaxis of childhood asthma, there is a dearth of information regarding the
      duration of treatment. The present study was undertaken to assess the possibility
      of successful withdrawal of inhaled corticosteroids in childhood asthma following
      good control of the disease. METHODOLOGY: The study was carried out at the Asiri
      Hospital, Colombo, Sri Lanka and was a prospective observational clinical study.
      The participants were consecutive children with documented moderately severe and
      severe asthma seen over a period of 4 years from January 1990 and followed up to
      December 2003. Patients were allocated randomly to receive either beclomethasone
      dipropionate or budesonide. Initial dose of the selected drug was 300, 400 or 600
      microg/day, depending on the child's age. After a period of stabilization, the
      dose was reduced from the starting dose to a maintenance level of 200, 300 or 400
      microg/day, respectively. Once sustained control had been maintained for a period
      ranging from 9 to 18 months, gradual withdrawal was attempted. The dosage was
      reduced by 50-100 microg each time, at intervals of 3 months. Long-term follow up
      was maintained following withdrawal of inhaled corticosteroids. Breakthrough
      wheezing, acute severe attacks, hospitalization for wheezing and absence from
      school were used to assess the response. RESULTS: Eighty-six children were
      recruited into the study. Eighty children responded well. The initial period on a
      high dose of corticosteroid was 8.4 months (range 4-12 months) and the average
      period of maintenance dosing was 11.7 months (range 9-18 months). The average
      time taken for withdrawal was 12.6 months (range 9-18 months). Successful
      withdrawal was achieved in 73 children. In this group, the mean total duration of
      treatment was 27.4 months (range 20-44 months). Up to December 2003, the subjects
      had been observed for an average period of 97.1 months (range 86-121 months)
      following withdrawal of inhaled corticosteroids. Of the 73 children in whom
      corticosteroids were withdrawn, 57 (78%) have remained well without any episodes
      of wheezing, and 14 (19%) have had mild episodes of wheezing that were easily
      controlled by bronchodilators. No patient needed hospitalization, long-term
      treatment or systemic corticosteroids. In two (3%) patients, it was necessary to
      restart inhaled corticosteroids because of troublesome recurrences. CONCLUSION:
      It is possible to gradually withdraw inhaled corticosteroids in a significant
      proportion of asthmatic children once good control has been sustained on a
      maintenance dose for a considerable period.

PMID- 15955155
TI  - Pulmonary involvement in Erdheim-Chester disease.
AB  - Erdheim-Chester disease is a disseminated non-Langerhans' cell histiocytosis
      involving multiple organs with characteristic sclerotic musculoskeletal lesions.
      This is the report of the case of a 53-year-old woman with extensive and
      progressive pulmonary disease. Computed tomography scans revealed diffuse
      infiltrative lung disease. Thoracoscopic lung biopsy and a biopsy of the right
      femur lesion were performed. The histopathology revealed that she had non
      Langerhans' cell histiocytosis; Erdheim-Chester disease. The characteristic
      lesions of Erdheim-Chester disease, including involvement of the orbit,
      pericardium, periaorta, and bone were detected. This helped to further confirm
      that the patient had Erdheim-Chester disease with associated pulmonary
      involvement. As Erdheim-Chester disease is a rare non-Langerhans' cell
      histiocytosis that may be misdiagnosed as interstitial lung disease or other
      pulmonary disorders, this diagnosis should be considered in the differential
      diagnosis of such lung lesions.

PMID- 15955156
TI  - Successful treatment of invasive pulmonary aspergillosis in an immunocompetent
      host.
AB  - Immunocompromised individuals are susceptible to pulmonary Aspergillus infection,
      but invasive Aspergillus infection is extremely rare in the presence of normal
      immunity. A case of invasive pulmonary aspergillosis in an immunocompetent 57
      year-old female who was successfully treated with liposomal amphotericin-B is
      reported here.

PMID- 15955157
TI  - Aspergillus pacemaker endocarditis presenting as pulmonary embolism.
AB  - Pacemaker endocarditis (PME) is a rare but severe complication of endocardial
      pacemaker implantation. Fungal PME is extremely uncommon. The case of a 66-year
      old female patient who was diagnosed as having a pulmonary embolus based upon the
      patient's clinical presentation and computed tomography angiography findings is
      presented. Transthoracic echocardiography demonstrated a huge vegetation attached
      to the pacemaker wire. The pacemaker system was removed surgically during
      cardiovascular bypass. The vegetation was cultured, the results of which were
      positive for Aspergillus spp. No risk factors for Aspergillus infection were
      found in the patient. She was treated with liposomal amphotericin B for 3 weeks,
      followed by itraconazole for 40 weeks. At 1 year later, the patient remains
      asymptomatic.

PMID- 15955158
TI  - Pneumocystis carinii pneumonia infection in a patient with known chronic
      mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis is a disorder of the skin, nails or mucous
      membranes in the absence of another cause of the infection. It is also associated
      with autoimmune endocrinopathies in 40% of patients. It is thought to be due to a
      T-cell defect, although no precise mechanism has been elucidated. There have been
      two previous cases of Pneumocystis carinii pneumonia reported with this
      condition. We report a fatal case in a 34-year-old male.

PMID- 15955159
TI  - Causes and management of pleural fibrosis.

PMID- 15955160
TI  - Familial spontaneous pneumothorax.

PMID- 15955162
TI  - Proceedings of the 8th Clinicopathological Conference on Renal Allograft
      Pathology. July 10, 2004, Tokyo, Japan.

PMID- 15955163
TI  - The morphological compensatory change of peritubular capillary network in chronic
      allograft rejection.
AB  - To clarify the compensatory hemodynamic alterations in the interstitium of renal
      allograft biopsies with chronic rejection, we evaluated the morphological changes
      in the peritubular capillary (PTC) network. Seven renal biopsy specimens from
      recipients with chronic rejection presenting with elevation of serum creatinine
      of 1.9 +/- 0.5 mg/dL were examined. Renal biopsy specimens from their counterpart
      donors were used as normal controls. In each specimen, non-pathological
      interstitial areas without fibrosis, tubular atrophy or cell infiltration were
      compared with pathological areas (PA) showing fibrosis and/or tubular atrophy
      using a computer image analysis. Morphological measurements revealed that the
      mean cut surface area of the PTC in the non-pathological and pathological
      interstitial areas in the recipient biopsies were significantly larger than that
      of the normal controls (p < 0.001 and 0.001, respectively). In the recipient
      biopsies, both of the mean cut surface areas of the tubules and PTC in the non
      pathological areas were significantly higher than those in the PA (p < 0.001).
      The mean glomerular diameter in the recipient biopsies was also significantly
      higher than that of the donors (p < 0.01). In this study, we provided
      pathological evidence for the compensatory interstitial and glomerular
      hemodynamic alterations in kidney graft with chronic rejection and the condition
      as single kidney.

PMID- 15955164
TI  - Post-transplant early recurrent proteinuria in patients with focal
      glomerulosclerosis--angiotensin II immunostaining and treatment outcome.
AB  - We reviewed the transplantation data and results of histopathological studies
      with additional angiotensin II (AII) immunostaining of renal graft biopsies of
      nine cases (10 grafts) with recurrent proteinuria and three controls without
      recurrent proteinuria that received renal transplantation for primary focal
      segmental glomerulosclerosis (FSGS) between 1986 and 2002. Recurrent FSGS was
      confirmed in six grafts from nine cases by light microscopy. In cases with
      recurrent proteinuria, loss of graft function was noted in all six renal grafts
      received between 1986 and early 1992 but in none of four grafts received between
      late 1992 and 2002. Two of four patients of the late group but none of those of
      the early group received angiotensin converting enzyme (ACEI) or angiotensin II
      receptor blocker (ARB) with plasma exchange (PE). In control cases without
      proteinuria, AII immunostaining was detected in tubules but not in glomeruli in 1
      hour biopsies as well as later on. In cases with recurrent proteinuria, AII
      immunostaining was detected in both tubules and glomeruli, although glomerular
      AII staining was not observed in 1-hour biopsies. Our results suggest that
      effective treatment of post-transplantation recurrent FSGS requires ACEI or ARB
      with PE in the absence of another etiology.

PMID- 15955165
TI  - Peritubular capillaritis in early renal allograft is associated with the
      development of chronic rejection and chronic allograft nephropathy.
AB  - Peritubular capillaritis (PTCitis) has been recognized as one form of
      acute/active allograft rejection, and its relation to humoral immunity has been
      suggested. However, its mechanisms remain to be fully clarified, and there are no
      criteria for evaluating the extent of PTCitis in a biopsied allograft. In this
      study, we first evaluated the extent of PTCitis in early allografts in patients
      presenting with acute cellular rejection (ACR) and antibody-mediated rejection
      (AbAR). We also included patients who showed no evidence of ACR and/or AbAR.
      Next, we investigated whether or not PTCitis persisted and if peritubular
      capillary basement membrane (PTCBM) thickening was present in their follow-up
      biopsy specimens. We adopted the scoring system of PTCitis, which was presented
      at the Seventh Banff Conference on Allograft Pathology in 2003. In total, 53
      patients were included in this study. At first biopsy, 17 showed ACR, eight
      showed AbAR, 16 showed mild PTCitis only, and 14 were without significant
      pathologic changes. The PTC score was the highest in the AbAR group, and in some
      patients the score gradually increased during the follow-up period. Similar
      changes were also observed in the group with mild PTCitis only. In late
      allografts, half of the patients with AbAR developed chronic rejection (CR), and
      the PTCBM score was the highest in that group. Surprisingly, CR was present in
      more than 30% of patients without ACR and/or AbAR but mild PTCitis only. In the
      control group, only a few showed CR and/or chronic allograft nephropathy (CAN).
      In conclusion, it became clear that we should carefully monitor for mild PTCitis
      in early allografts. In addition, our data also proved the usefulness of the PTC
      score and PTCBM score.

PMID- 15955166
TI  - Complement C4d deposition in transplanted kidneys: preliminary report on long
      term graft survival.
AB  - The effects of antibody-mediated rejection on long-term graft survival have not
      been fully investigated. The aim of this study is to clarify the influence on
      long-term survival of deposition of the complement split product C4d in
      allografts using polyclonal anti-C4d antibody. Inclusion criteria were recipients
      who underwent graft biopsy during acute deterioration of graft function within
      the first 2 yr after transplantation. Patients whose graft did not survive more
      than 1 yr and who received graft from an human leucocyte antigen (HLA)-identical
      sibling or an ABO-incompatible donor were excluded. Among the 92 recipients
      investigated, 22 (23.9%) had peritubular capillary C4d deposition, 15 (16.3%) had
      glomerular capillary C4d deposition and seven (7.6%) had both peritubular and
      glomerular capillary C4d deposition. Twenty of these 22 patients revealed acute
      cellular rejection, including borderline changes. There was no significant
      relationship between pathological severity of acute rejection and presence or
      absence of peritubular capillary C4d deposition. Graft survival was inferior in
      patients with peritubular capillary C4d deposition to that in patients without
      C4d deposition (p = 0.0419). Graft survival in patients with glomerular C4d
      deposition did not differ from that in patients without C4d deposition. In
      conclusion, C4d deposition in peritubular capillaries has a substantial impact on
      long-term graft survival.

PMID- 15955167
TI  - Long-term course of post-transplant mesangial IgA deposition: clinicopathologic
      study of nine cases.
AB  - We conducted the present study to elucidate the fate of post-transplant mesangial
      IgA deposit under the long-term observation. Out of a total of 45 cases with post
      transplant mesangial IgA deposition, nine cases with more than 4 yr of follow-up
      term were enrolled in this study, and clinicopathologic characteristics were
      described. The study included three men and six women with a mean age of 34.2 yr.
      The average observation time from the detection of mesangial IgA deposition was
      6.1 yr. Three cases were categorized as recurrent IgA nephropathy, while six
      cases were classified into latent mesangial IgA deposition. One case with
      hypertension developed end-stage renal disease. The significant improvement in
      microscopic hematuria was observed in one recurrent IgA nephropathy case.
      Microscopic findings included mild mesangial stalk thickening in all but one
      case. IgA deposition demonstrated a significant decrease in three latent
      mesangial IgA deposition cases. No apparent reduction in dense deposit quantity
      was observed on electron microscopy. There was no association between
      clinicopathologic findings and the regimen of anti-immunosuppressive agents. This
      study showed the improvement of the disease activity did occur in both recurrent
      IgA nephropathy and latent mesangial IgA deposition. Further investigation of
      latent mesangial IgA deposition may present the important clue to the
      pathogenesis of IgA nephropathy.

PMID- 15955168
TI  - Latent IgA deposition from donor kidney is the major risk factor for recurrent
      IgA nephropathy in renal transplantation.
AB  - BACKGROUND: Previous studies have recognized risk factors for recurrent IgA
      nephropathy (r-IgAN) in renal transplantation. However the clinical significance
      of latent IgA deposition from the donor kidney remains to be determined. PATIENTS
      AND METHODS: Between 1992 and 1999, 0-hour allograft biopsies were performed in
      510 renal transplantation recipients at the Kidney Center of Tokyo Women's
      Medical University. Among these 510 patients, there were 49 whose primary disease
      was identified as IgAN. Among these 49 patients, 13 patients (26.5%) were
      diagnosed as having r-IgAN based on renal biopsy. We compared risk factors of r
      IgAN, including IgA deposition, between the r-IgAN and non-r-IgAN groups.
      RESULTS: We assessed factors previously reported to be risk factors for r-IgAN,
      such as follow-up period after transplantation, sex, ages of donors and
      recipients, donor type, ABO compatible or incompatible transplantation, number of
      HLA-A, B, and DR mismatches, number of donors with HLA-A2, B35, B46, and/or DR4,
      duration to end stage renal disease, duration of dialysis, and latent IgA
      deposition from donor kidneys. Latent IgA deposition was the only risk factor
      that differed significantly in frequency between patients with and without
      recurrence (38.5% in r-IgAN group vs. 9.1% in non-r-IgAN group, p = 0.037). Other
      factors did not differ significantly between the two groups. Clinical factors,
      such as urinary protein excretion, urinary red blood cell sediment and serum
      creatinine, were significantly worse and the number of patients who required
      hemodialysis 5 yr after transplantation was significantly higher in the r-IgAN
      group than in the non-r-IgAN group (38.5 vs. 5.6%, p = 0.001). Four of the five
      patients who required hemodialysis in the r-IgAN group had latent IgA deposition
      from the donor kidney. CONCLUSION: Our data suggest that 26.5% out of patients
      with primary IgAN will develop recurrence within 5 yr after transplantation.
      Latent IgA deposition from the donor kidney was one of the risk factors of r-IgAN
      and it would lead to the development of r-IgAN. Moreover, r-IgAN will compromise
      graft survival, especially in cases with latent IgA deposition from the donor
      kidney.

PMID- 15955169
TI  - Clinicopathological evaluation of renal allograft treated with anti-CD25
      monoclonal antibody.
AB  - Twenty-seven living-donor kidney recipients were treated with the antibody
      against CD25 as the induction immunosuppressive agent. They did not develop acute
      rejection within 1 month after transplantation, and mean serum creatinine level
      at 1 month was 1.0 +/- 0.4 mg/dL. There were no findings of acute rejection or
      drug-induced nephrotoxicity in protocol biopsies at 1 month following
      transplantation. After 1 month had passed, acute rejection occurred in three
      cases. The pathological grade of acute rejection varied from borderline to grade
      III by Banff classification. The careful inspection is necessary to find out the
      occurrences of acute rejection more than 2 months after transplantation because
      immunological situation has been changing around this period.

PMID- 15955170
TI  - Quadruple immunosuppression with basiliximab, tacrolimus, mycophenolate mofetil
      and prednisone is safe and effective for renal transplantation.
AB  - INTRODUCTION: Recent immunosuppression with tacrolimus and mycophenolate mofetil
      has improved the results of renal transplantation. In this study, we analyzed the
      effect and safety of basiliximab as an induction therapy. MATERIAL AND METHODS:
      Forty-nine kidney recipients were given tacrolimus, mycophenolate mofetil and
      prednisone (non-Bas group), and 31 recipients were given basiliximab as an
      induction therapy in addition to the triple immunosuppressants (Bas group). Graft
      function, incidence of acute rejection (AR), findings of protocol graft biopsy
      and adverse effects were compared. RESULTS: Serum creatinine within 1 yr post
      transplant was comparable between the two groups. Incidence of biopsy-proven AR
      within 6 months post-transplant was less in the Bas group than in the non-Bas
      group. Borderline change at 3 months post-transplant was less in the Bas group
      when compared to the non-Bas group. The frequency and severity of tubulitis were
      higher in the non-Bas group than in the Bas group. The addition of basiliximab
      did not increase opportunistic infection, but reduced tacrolimus nephrotoxicity.
      CONCLUSION: The addition of basiliximab to the tacrolimus-based triple
      immunosuppressive regimen enabled us to reduce the doses of immunosuppressants
      and tacrolimus nephrotoxicity without increasing early rejection or infection.
      This regimen is safe and effective for application during the early period after
      renal transplantation.

PMID- 15955171
TI  - Recurrent nephrotic syndrome after living-related renal transplantation resistant
      to plasma exchange: report of two cases.
AB  - We encountered two patients of recurrent nephrotic syndrome (NS) after renal
      transplantation that was resistant to plasma exchange (PEX). Case 1 was a 34-year
      old man with a living-related renal transplant for type-I membranoproliferative
      glomerulonephritis (MPGN) related end-stage renal disease (ESRD). He developed
      overt proteinuria 7 months post-transplant and presented with NS 5 months later.
      Biopsy of the transplant kidney revealed recurrent type I MPGN, but no features
      of acute rejection (AR) or chronic allograft nephropathy (CAN). He was treated
      with cyclophosphamide (CP), oral prednisolone (40 mg/d), an anti-platelet agent,
      heparin sulfate, and PEX, but the nephrotic state persisted and renal function
      was deteriorated. He recommenced hemodialysis 3 yr and 9 months after renal
      transplant. Case 2 was a 47-year-old male who underwent living-related renal
      transplant for ESRD due to focal segmental glomerulosclerosis (FSGS). He
      presented with proteinuria shortly after renal transplantation. He also had
      frequent episodes of AR. Graft biopsy revealed recurrent FSGS. Treatment of pulse
      methylprednisolone and PEX was transiently effective, but NS relapsed shortly
      after PEX. Graft biopsy at our hospital showed features of CAN with moderate
      interstitial fibrosis and tubular atrophy, presence of intraglomerular foam cells
      but no segmental sclerosis. Treatment with 12 courses of low-density lipoprotein
      apheresis (LDL-A) reduced proteinuria from 9.6 to 2.0 g/d, and incomplete
      remission has been maintained for more than 1 yr after LDL-A with slowly
      progressive renal dysfunction. Despite recent therapeutic advances, including the
      use of immunosuppressants and PEX, treatment of recurrent disease remains
      difficult. The LDL-A might be useful in cases with recurrent FSGS resistant to
      PEX.

PMID- 15955172
TI  - A case of acute humoral rejection with various depositions of C4d, IgG, IgM, and
      C3c in peritubular capillaries and/or glomerular capillaries.
AB  - A 41-year-old Japanese male patient with end-stage renal disease received ABO
      compatible living related kidney transplantation from his sister on April 2003.
      The kidney functioned immediately after kidney transplantation. Protocol
      allograft biopsy at 1 yr after kidney transplantation was performed on April
      2004. His serological data was not particular and he did not suffer with chronic
      inflammation. The allograft biopsy specimen revealed moderate accumulations of
      polymorphonuclear leukocytes in peritubular capillaries (PTCs), dilatation of
      PTCs and moderate infiltrations of polymorphonuclear and/or mononuclear cell in
      glomeruli (Transplant glomerulitis, moderate). Immunofluorescent study (IF) of a
      frozen section of the allograft biopsy specimen showed a strong, diffusely
      distributed endothelial-staining pattern in PTCs for C4d. The C4d was also
      strongly detected in a linear glomerular basement membrane (GBM) pattern. And
      widespread moderate C3c deposits, weak IgM, and IgG deposits were also seen in
      PTCs. Immunofluorescent study also showed granularly peripheral and mesangial
      deposits of strong IgM, C1q, and moderate IgG in glomeruli, IgA and C3c were
      faintly positive. The panel reactive antibody, which had been negative before
      transplantation, was positive for both HLA classes I and II at that time. We
      diagnosed as acute humoral rejection (AHR) and he was treated with course of
      steroid pulses and 5 d of gusperimus (DSG); and a total of three times Plasma
      exchange (PE) treatment was added. The level of serum creatinine, once increased
      to 1.7 mg/dL, decreased gradually to 1.4 mg/dL. He has a stable graft function.
      This is the only case of various depositions of immunoglobulins and complements
      in PTC and/or glomerular capillaries during AHR.

PMID- 15955173
TI  - Renal graft loss with plasma cell-rich acute rejection in cadaveric renal
      transplantation: a case report.
AB  - We reported a case of renal graft loss in cadaveric renal transplantation. An
      episode biopsy with renal dysfunction showed plasma cell predominant inflammatory
      infiltration in the interstitium without a finding of vascular or glomerular
      rejection, and was diagnosed as plasma cell-rich acute rejection (PCAR). Despite
      intensive immunosuppressive therapy, the renal histology of repeated biopsies
      showed persistent plasma cell infiltration and the graft was finally lost.
      Immunohistological staining and immunoglobulin gene rearrangement studies to
      estimate the clonality of inflammatory cells revealed that the infiltrating
      plasma cells were polyclonal in origin. Epstein-Barr virus was not detected by in
      situ hybridization. From these results, we excluded the possibility of post
      transplant lymphoproliferative disorder (PTLD); however, a precise definition and
      differential diagnosis between PCAR and PTLD has not yet been fully determined.
      As therapeutic regimens for PCAR and PTLD are different, definite guidelines for
      diagnosis and treatments of PCAR need to be established.

PMID- 15955174
TI  - A new concept of accommodation in ABO-incompatible kidney transplantation.
AB  - This work focuses on the mechanism of acute antibody-mediated rejection leading
      to graft loss and the mechanisms of accommodation permitting graft survival in
      ABO-incompatible kidney transplantation. As previously noted, accommodation
      occurs only with (i) post-transplant suppression of glycosyltransferase, a
      product of ABO histo-blood group genes in the graft and (ii) prevention of
      antigen-antibody reactions and delayed hyperacute rejection due to reduced
      antigenicity of enzyme-regulated histo-blood group antigens. This article
      discusses the mechanism of ABO histo-blood group glycosyltransferase suppression.
      Accommodation is always established in successful ABO-incompatible organ grafts
      and ABO-minor mismatch bone marrow transplantation. In the former, accommodation
      develops even though ABO histo-blood types of the recipient and the donor are
      incompatible. In the latter, infusion of donor-derived bone marrow causes the
      recipient's blood to be eventually replaced by blood of the donor's type.
      However, the recipient's organs retain their original tissue type. In successful
      bone marrow engraftment, accommodation is established regardless of ABO
      incompatibility. In organ transplantation the recipient's ABO histo-blood type
      regulates the graft's ABO histo-blood type, while in bone marrow transplantation
      the new ABO histo-blood type from the donor suppresses and regulates the ABO
      histo-blood type in recipient organs. In other words, bone marrow-derived histo
      blood type regulates the histo-blood type of the organs.

PMID- 15955175
TI  - How quickly can a renal transplant pathological diagnosis be completed? The
      demands of clinicians and the objections of pathologists.
AB  - This analyzer symposium was held in order to clarify whether pathologists were
      satisfying the demands of clinicians in renal transplant care in Japan. Thirty
      one questions were prepared as to "Background", "Transplant results", "Basic
      issues concerning renal transplant biopsy diagnoses", "Renal transplant biopsy
      and diagnosis, and actual treatment", and "Diagnostic support". By analyzing the
      answers of all the questions, the current status of renal transplant treatment in
      Japan has been clarified as follows. Most institutions can produce a renal
      transplant optical microscope section 1 or 2 days after the biopsy. Over 90% of
      those on the clinical side would like to have the diagnosis on the same day as
      the biopsy or at the latest the day after. Therefore, in fact a 24 hour time lag
      was observed between the pathological diagnosis and the request from the clinical
      side. No clinicians required a pathologist to decide whether to perform a
      transplant or not. Nearly all clinicians provide treatment based on the renal
      transplant biopsy diagnosis. As renal transplant pathological diagnosis is
      difficult, all pathologists need a diagnostic support system. The creation of
      this system was thought to be a pressing matter.

PMID- 15955176
TI  - Abstracts of the American Society for Neurochemistry, 36th Annual Meeting,
      Madison, Wisconsin, USA, 25-29 June, 2005. Abstracts.

PMID- 15955178
TI  - Left ventricular lead performance in cardiac resynchronization therapy: impact of
      lead localization and complications.
AB  - INTRODUCTION: Cardiac resynchronization therapy (CRT) using left ventricular (LV)
      pacing from the coronary sinus tributary is increasingly and frequently used in
      patients with severe congestive heart failure. The present study investigates LV
      lead performance in different anatomic locations. METHODS: The LV pacing site was
      defined by bi-plane fluoroscopy. In the left anterior oblique view, the coronary
      sinus is encircling the mitral ring with the tributaries radiating out like the
      hands of a watch. Using this clockwise method, Group A had an LV pacing site
      before 3 o'clock and Group B at or after 3 o'clock. In right anterior oblique
      view, the LV was divided into three segments: basal, mid-ventricular, and apical.
      RESULTS: LV lead implantation was successful in all of 120 consecutive patients.
      Mean follow-up was 16.7 months. Implantation time decreased from mean 190 to 80
      minutes during the period (P = 0.01). The mean LV lead stimulation threshold
      increased initially and stabilized afterwards. The threshold measured at last
      follow-up was higher than at implantation (2.3 vs 2.7 microJ, P = 0.04). Useful
      venograms were obtained in 94 patients. No significant difference in thresholds
      was observed between Groups A and B. Phrenic nerve stimulation was most commonly
      seen in Group B (8/70 vs 1/24, P = 0.001). CONCLUSION: Implantation of an LV lead
      for CRT is possible in patients with congestive heart failure and associated with
      an acceptable low complication rate. LV lead implantation is associated with a
      learning curve. At mid-term follow-up, LV lead performance is stable and
      unrelated to the LV implantation site.

PMID- 15955179
TI  - Use of preshaped sheath to plan and facilitate cannulation of the coronary sinus
      for the implantation of cardiac resynchronization therapy devices: preshaped
      sheath for implantation of biventricular devices.
AB  - OBJECTIVES: The aim of the study is to describe a new technique for facilitating
      the implantation of cardiac resynchronization therapy (CRT) devices. BACKGROUND:
      CRT, by simultaneous pacing of the right and left ventricles has proven to be a
      useful treatment for patients with advanced heart failure and left ventricular
      (LV) systolic dysfunction, who have concomitant LV dyssynchrony. One of the
      greatest challenges to the wide applications of this therapy has been the
      technical difficulty encountered with implantation of the left ventricular lead.
      This is mainly due to the varied anatomy of the coronary venous system, which is
      further complicated by distortion of the anatomy in patients with advanced heart
      failure. METHODS: Details of the coronary venous anatomy are initially assessed
      by cannulating the coronary sinus (CS) using a specialized long preshaped sheath
      introduced from the femoral approach. Occlusive venography is performed in three
      views, and then the guide wire or the deflated balloon catheter is left in the CS
      for guidance. The most suitable equipment for the anatomy is chosen. Then, the
      operative site is prepped and the CS is approached from above. RESULTS: From
      November 2003 until December 2004, we have used this approach on all patients
      presenting for CRT device implantation at Prince Sultan Cardiac Center (n = 25).
      The CS was cannulated using the preshaped catheter in less than 5 minutes in all
      cases. After delineation of the anatomy, successful CRT implantation was achieved
      in all patients. Mean procedure time for the implantation was 110 +/- 18 minutes.
      Uncomplicated minor CS dissection related to the use of the preshaped sheath was
      observed in 1 patient without consequences. CONCLUSIONS: The use of preshaped
      sheath from the femoral approach facilitates planning the successful and safe
      implantation of CRT systems.

PMID- 15955180
TI  - Utilization of intracardiac echocardiography to access the coronary sinus for
      left ventricular lead placement.
AB  - This is a presentation of a case series of 10 consecutive patients undergoing
      implantation of cardiac resynchronization therapy defibrillator (CRT-D).
      Intracardiac echocardiography (ICE) is utilized to gain access to the coronary
      sinus. The method used is detailed with a brief discussion of observations gained
      from this early experience.

PMID- 15955181
TI  - Detection of the defibrillation threshold using the upper limit of vulnerability
      following defibrillator implantation.
AB  - OBJECTIVE: This study was designed to test defibrillation threshold (DFT) with
      the least number of fibrillation inductions using upper limit of vulnerability
      (ULV) and to describe the most practical set of ICD during DFT following
      implantation. BACKGROUND: Although the correlation between ULV and DFT has been
      well described, there has been no uniform DFT testing protocol taking the
      advantage of ULV after defibrillator (ICD) implantation. METHODS: A total of 26
      patients undergoing a new ICD implantation had a DFT induced with scanned T wave
      shock. The hypothesis that ventricular fibrillation (VF) could be defibrillated
      with 5 J higher than the highest T wave shock needed to induce VF or with 10 J if
      the T wave shock needed to induce VF was less than 5 J, was tested and 20
      patients fulfilled these criteria. The methodology is improved by detecting peak
      T wave with 12-lead ECG, applying biphasic T wave shock and scanning the T wave
      shock in a wider window. RESULTS: Five patients in the first group (n = 15) and
      one patient in the second group (n = 11) did not fulfill the above hypothesis.
      The common features of six patients who did not fulfill the hypothesis were that
      T wave shock needed to induce VF was either under 5 J (5 patients) or high (1
      patient). CONCLUSION: This study revealed the importance of methodology in
      studies regarding ULV and DFT. Following ICD implantation, we propose the first
      biphasic T wave detected by 12-lead ECG and rescue shock set at 10 and 15 J,
      respectively. If any of the scanned T wave (40 ms before and 40 ms after the peak
      T wave with decrements and increments of 20 ms) shocks could not induce VF, then
      the T wave and the first rescue shock should be set at 5 and 10 J, respectively.
      If the induction of VF has been unsuccessful with T wave shock at 5 J, then a
      safe defibrillation with 10 J should be expected in majority.

PMID- 15955182
TI  - Characteristics associated with low treatment satisfaction in patients with
      implanted cardioverter defibrillators: results from the LICAD study.
AB  - The evaluation of low treatment satisfaction (LTS) with an implanted cardioverter
      defibrillator (ICD) remains a neglected area of clinical research. However, a
      trustful attitude toward an ICD is crucial. Within the scope of ICD health
      technology assessment, we searched for predictors of LTS. Of 195 ICD patients
      enrolled (mean 59.8 years, standard deviation 12.6), 163 (83.6%) were men and 26
      (16.4%) were women. We measured anxiety, helplessness, and depression with
      standardized instruments and LTS with 11 dichotomous items concerning a
      mistrustful attitude, a negative body image, and low appraisal. A total of 47
      (24.1%) patients were considered as LTS patients. Multivariate logistic
      regression was used for assessment of LTS. Adjusted for age and survey, LTS was
      significantly more prevalent in depressed, anxious, and phobic patients.
      Multivariate logistic regression including medical and psychological covariates
      revealed the experience of > or =5 shocks with an odds ratio (OR) of 10.17 (95%
      CI 3.57-29.00, P < or = 0.001), being employed with an OR of 8.07 (95% CI 2.39
      27.19, P < or = 0.001), and feelings of helplessness (OR 4.61, 95% CI 1.79-11.90,
      P < or = 0.002) as the most important predictors for LTS. Women had a slightly
      not significant effect on LTS. Age, educational status, and depression were not
      significant. LTS patients required more support for living with the ICD (P < or =
      0.001). Thus, LTS serves as surrogate measure for deteriorated psychic health.
      Clinicians should be advised to identify LTS patients and to consider
      psychotherapeutic counseling for them.

PMID- 15955183
TI  - Effect of inter-electrode distance on bipolar intramural radiofrequency ablation.
AB  - OBJECTIVES: We aimed at evaluating bipolar radiofrequency ablation by correlating
      inter-electrode distance (ILD) with lesion dimensions and continuity. BACKGROUND:
      Previous reports indicated that bipolar radiofrequency (RF) current applied to
      two adjacent sites in vitro, synergistically increased lesion sizes greater than
      that observed for unipolar RF current delivery using the same electrodes.
      METHODS: Ablations were performed intramurally to ensure that each electrode
      surface (radius = 0.4 mm, area = 3.52 mm(2)) provided consistent contact with the
      myocardium. Ninety-six ablations were performed in four greyhounds using bipolar
      ablation needles with ILDs of 1, 2, 3, and 4 mm. An epicardial approach was used
      to ensure accurate positioning of the needles within the myocardium. Lesions were
      created using temperature-controlled RF delivery for a duration of 60 seconds to
      achieve 90 degrees C at the electrode proximal to the needle base. Lesion
      dimensions were determined histologically. RESULTS: Increasing the ILD, decreased
      lesion width (P = 0.003) but increased lesion depth (P = 0.001). Lesions remained
      continuous with ILDs of 1-3 mm but became discontinuous at 4 mm. Energy
      requirements during ablation increased with increasing ILDs. CONCLUSION: Using
      the above parameters (electrode radius, RF power delivery, time) during bipolar
      ablation, lesion continuity was critically dependent on the ILD. The maximum ILD
      threshold to create contiguous overlapping lesions was 3 mm. Lesions of greater
      width were created using shorter ILDs. Clinically, greater control over lesion
      dimensions can be obtained by manipulating the ILD distance.

PMID- 15955184
TI  - Reduction of right ventricular pacing in patients with sinus node dysfunction
      using an enhanced search AV algorithm.
AB  - BACKGROUND: Dual chamber pacing typically results in a high percentage of
      ventricular pacing. A number of studies have been conducted suggesting
      detrimental effects of ventricular desynchronization produced by long-term RV
      pacing. Pacemaker algorithms that extend the AV interval to uncover intrinsic AV
      conduction have been utilized to reduce ventricular pacing. These algorithms are
      often limited to AV intervals below 250 ms limiting the ventricular pacing
      reduction. We hypothesized that by allowing AV intervals to extend beyond 300 ms,
      a marked reduction in RV pacing can be achieved. METHODS: A total of 30 patients
      (17 men, mean age 71 +/- 9) with standard Brady indications, and implanted with a
      Medtronic Kappa 700 pacemaker, were randomized to 2-week treatments with default
      Search AV (KSAV) parameters or Enhanced Search AV (ESAV) parameters. The Enhanced
      Search AV algorithm included the capability for continuous adjustment of AV
      delays and the ability to auto disable in patients with persistent AV block.
      RESULTS: Among patients with intact AV conduction, percent VP was greater in KSAV
      versus ESAV (70 +/- 40% vs 19 +/- 28%, P < 0.001). In patients with persistent AV
      block, the algorithm suspended appropriately and there was no significant change
      in the percent VP between both arms of the study. In 18/22 patients, percent VP
      was reduced below 40%. CONCLUSIONS: Substantial reduction in ventricular pacing
      can be achieved by allowing the AV interval parameters to extend beyond 300 ms
      using the ESAV algorithm. In patients with AV block, ESAV suspended and patients
      were paced at their nominal settings.

PMID- 15955185
TI  - Cerebral oxygenation during defibrillator threshold testing of implantable
      cardioverter defibrillators.
AB  - BACKGROUND: The induction of ventricular fibrillation (VF) during defibrillator
      threshold testing of implantable cardioverter defibrillators (ICD) provokes
      global cerebral hypoperfusion and impaired oxygen delivery. Limited data are
      available on the neurophysiological effects of defibrillator threshold testing.
      Near infrared spectroscopy (NIRS) can noninvasively measure changes in specific
      chromophores, which reflect cerebral oxygenation at the intravascular and
      mitochondrial levels. We performed a prospective trial using NIRS to analyze
      cerebral cortical oxygenation during defibrillator threshold testing. METHODS:
      Eleven patients (men = 9; age = 64 +/- 11 years: LVEF = 44 +/- 11%) underwent
      subpectoral ICD implantation and defibrillator threshold testing under general
      anesthesia. A NIRO 300 spectrometer was used to measure the absolute changes in
      the concentrations of oxyhemoglobin, de-oxyhemoglobin, and cytochrome c oxidase
      copper moiety during each procedure. The mean arterial blood pressure was
      monitored simultaneously. RESULTS: The mean number of defibrillator threshold
      tests was two (range 2-6). Twenty-six episodes of VF (duration 13.1 +/- 9.7
      seconds; cycle length 230.2 +/- 20.8 ms) and two episodes of VT (duration 15 +/-
      2.8 seconds; cycle length 320 +/- 11.3 ms) were induced. Each episode of VF and
      VT resulted in a decrease in the mean arterial blood pressure to 23.9 +/- 7.5
      mmHg (p < or = 0.05) and oxyhemoglobin (-4.2 +/- 1.7 micromol/L; p < or = 0.05)
      and an increase in de-oxyhemoglobin (2.7 +/- 1.4 micromol/L). There was no change
      in the cytochrome c oxidase copper moiety redox status (0.09 +/- 0. 30
      micromol/L). CONCLUSION: Our results suggest that impaired oxygen delivery during
      induced VF and VT does not affect oxygen availability at the cellular intra
      mitochondrial level.

PMID- 15955186
TI  - Brain perfusion assessed by 99mTc-ECD SPECT imaging in pediatric patients with
      neurally mediated reflex syncope.
AB  - BACKGROUND: The involvement of cardiogenic and neurogenic mechanisms in neurally
      mediated reflex syncope is well documented. In our previous studies in patients
      with neurally mediated reflex syncope, we have found evidence for differential
      regulation of the noradrenergic receptors in tilt-positive and tilt-negative
      patients. The present work concentrates on the observations of differences in
      regional brain perfusion using brain SPECT via injecting the patient at the
      completion of the tilt test. METHODS AND RESULTS: The following study was
      designed to assess the reduction and regional differences in cerebral blood flow
      by means of SPECT using technetium-99m labeled V-oxo-1,2-N1ethylenedylbisl
      cysteine diethylester (ECD) in patients with an injection during tilt testing.
      Twenty patients with NMS were included in the study with a mean age of 12.2 years
      (age range; 8-16 years). HUT was positive in 10 patients and negative in 10
      patients. When tilt (+) and tilt (-) were evaluated together, regional
      cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical
      areas with highest variability of perfusion index in left frontoparietal cortex.
      The lowest perfusion index values were observed in the left anterior frontal
      region followed by the left prefrontal-frontoparietal-anterior, parietal-orbito
      frontal, and anterior temporal regions where perfusion is predominantly supplied
      via the anterior and middle cerebral arteries, while these differences did not
      reach statistical significance in a single dominant region compared to the other
      regions examined using ANOVA (P > 0.05) with this sample size. Decreases in
      [99mTc]ECD uptake were more widespread regionally on the left hemisphere than
      were decreases in right side of the brain. However when tilt- and tilt+ groups
      were compared, perfusion was significantly lower in the right periinsular
      posterior parietal and temporal regions (P < 0.05) in tilt + group. CONCLUSION:
      These tilt induced regional differences in brain perfusion suggest the distinct
      roles of middle cerebral artery dominant territory-related vasodepressor
      compensation mechanisms in neurally mediated reflex syncope phenomena where
      cerebral lateralization of cardiac control and insular ischemia may play an
      important role.

PMID- 15955187
TI  - Electromagnetic interference of implantable unipolar cardiac pacemakers by an
      induction oven.
AB  - Induction ovens have been reported to exert electromagnetic interference on
      implanted cardiac pacemakers. In an attempt to quantitatively investigate the
      electromagnetic interference caused by an induction oven on implantable unipolar
      cardiac pacemakers, we measured the distribution profile of the magnetic field
      intensity, both with and without a pan on the induction oven. We also performed
      the inhibition test and asynchronous test using four kinds of pacemakers housed
      in the standardized Irnich human body model, and measured the maximal distance
      from the induction oven up to which the interference occurred. In the pan
      detection mode of the oven in the absence of a pan, the distribution profile of
      the magnetic field intensity peaked at the center of the cooking plate, and
      during induction heating of a pan placed on the induction oven, it was the
      largest at the circular top-edge of the pan. Pacemaker pulses were inhibited by
      the induction oven, or generated by the reversion mechanism. The maximal
      interference distance from the oven was 34 cm for one of the pacemakers. Thus,
      the safe distance from an induction oven of a patient with an implanted cardiac
      pacemaker is considered to be 50 cm or more. In conclusion, in the pan-detection
      mode of the oven in the absence of a pan, the distribution profile of the
      magnetic field intensity peaked at the center of the cooking plate, and during
      the induction heating of a pan placed on the oven, it peaked at the circular edge
      of the pan. The induction oven asynchronized or generated pulses in implantable
      unipolar cardiac pacemakers up to a maximal distance of 34 cm from the induction
      oven.

PMID- 15955188
TI  - Prevalence and clinical course of the juveniles with Brugada-type ECG in Japanese
      population.
AB  - BACKGROUND: Although many studies on Brugada syndrome have been done, with many
      reports of genetic findings and clinical features, little evidence exists to
      support the role of this syndrome in sudden cardiac death in a juvenile
      population. We sought to determine the prevalence and clinical course in children
      exhibiting Brugada-type ECG in a community-based population. METHODS: Our study
      population comprised 21,944 subjects (11,282 boys and 10,662 girls) who underwent
      ECG during their first-year elementary school health examinations between 1992
      and 2001 in Izumi City, Osaka. Brugada-type ECG was defined as demonstrating ST
      segment elevation (coved or saddle-back type, J wave amplitude > or =0.2 mV) in
      the right precordial leads. We also divided Brugada-type ECGs into three types
      according to a consensus report. Type 1: coved ST-segment elevation displaying
      high J wave amplitude followed by a negative T wave; Type 2: high take-off and
      gradually descending ST-segment elevation (remaining > or =1 mm) followed by a
      positive or biphasic T wave; and Type 3: ST-segment elevation of <1 mm of both
      types. RESULTS: Four subjects showed Brugada-type ECG (0.02%) (2 boys and 2
      girls). Only one subject, a girl, met Type 1 criteria (0.005%). No history of
      structural heart disease was documented in these four subjects. During 6.8 +/-
      1.0 years of follow-up, no episode of unexpected sudden death, syncopal attack,
      and fatal arrhythmia occurred. CONCLUSIONS: The prevalence of Brugada-type ECG in
      a juvenile population was extremely low. To investigate when the typical Brugada
      type ECG might be manifested, it could be necessary to check ECGs after
      adolescence.

PMID- 15955189
TI  - Electrogram configuration and detection of supraventricular tachycardias by a
      morphology discrimination algorithm in single chamber ICDs.
AB  - BACKGROUND: Inappropriate ICD therapy for supraventricular tachycardia (SVT)
      remains a significant problem. A morphology-based algorithm (Wavelet) compares
      baseline and tachycardia electrograms (EGM). For this analysis different EGM
      sources can be programmed. This study evaluates the performance of Wavelet using
      two different EGM configurations (SVC-Can and RV-Can) for the detection of
      exercise-induced SVT. METHODS: Patients with a Medtronic model 7230 single
      chamber ICD and a dual coil lead were included. For each EGM source (SVC-Can or
      RV-Can), a baseline EGM template was acquired and the morphology similarity to
      this template (match percentage) was evaluated for 10-15 beats at different heart
      rates during exercise testing. The lower VT detection limit was programmed to 600
      ms (therapies off). RESULTS: A total of 28 patients (66.9 +/- 4.7 years, 93% men)
      and 5,824 intracardiac QRS complexes were analyzed. With the RV-Can source, a
      consistently high similarity to the baseline EGM template was observed (< or =100
      bpm: 90.90 +/- 0.56%; >100 bpm: 90.24 +/- 0.55%, P > 0.05). In contrast, SVC-Can
      was associated with a lower match percentage at baseline and a significant
      decrease at higher heart rates (< or =100 bpm: 77.91 +/- 2.65%; >100 bpm: 59.05
      +/- 5.65%, P < 0.005). Accordingly, the specificity for appropriate detection of
      exercise-induced SVT was higher with RV-Can (21/21 episodes) than with SVC-Can
      (8/18 episodes, specificity 100% vs 44%; P < 0.0001). CONCLUSION: The RV-Can
      configuration appears to be superior to SVC-Can as EGM source for appropriate SVT
      detection with the Wavelet algorithm.

PMID- 15955190
TI  - Pacing-induced electrophysiological remodeling in hypertrophic obstructive
      cardiomyopathy--observations on cardiac memory.
AB  - BACKGROUND: Hypertrophic cardiomyopathy carries an increased risk for sudden
      cardiac death. While pacing therapy reduces the left ventricular outflow tract
      gradient and improves symptoms in a subgroup of hypertrophic obstructive
      cardiomyopathy (HOCM) patients, its electrophysiological consequences are unknown
      and were therefore assessed in this prospective study. METHODS AND RESULTS:
      Fifteen consecutive HOCM patients were studied and compared with 14 patients
      without HOCM paced because of sinus bradycardia. ECG intervals were measured
      before pacemaker implantation and after > or =3 months of DDD pacing in HOCM
      patients and > or =5 weeks in controls. Both groups showed similar ECG signs of
      cardiac memory development. In HOCM patients, with baseline QTc 447 +/- 33 ms,
      cardiac memory development was not associated with any significant changes in ECG
      intervals. In contrast, baseline repolarization in control patients was
      significantly prolonged by 6% (QTc 429 +/- 33 vs 454 +/- 46 ms; P < 0.05).
      Furthermore, in HOCM patients repolarization was 7% shorter during DDD pacing
      compared to sinus rhythm (JTc 329 +/- 25 vs 353 +/- 21 ms; P < 0.05), despite a
      significantly prolonged ventricular activation time (QRS duration 155 +/- 16 vs
      91 +/- 9 ms; P < 0.01). CONCLUSIONS: Importantly, the development of cardiac
      memory-induced different repolarization responses depending on baseline structure
      and electrophysiology. In HOCM patients repolarization was shorter during right
      ventricular apical pacing than during normal activation despite prolonged
      activation time.

PMID- 15955191
TI  - Wide and narrow QRS complex tachycardia with identical heart rates: what is the
      mechanism?

PMID- 15955192
TI  - Mysterious loss of resynchronization during biventricular pacing.

PMID- 15955193
TI  - Development of implantable devices for continuous ambulatory monitoring of
      central hemodynamic values in heart failure patients.
AB  - BACKGROUND: Care and management of patients with congestive heart failure (CHF)
      is a major health-care challenge. The value of acute hemodynamic data in
      assessing heart failure has been questioned in some studies, while more intensive
      hemodynamic monitoring has been reported to improve patient care in others. A
      series of patient studies are reported here that were conducted to identify
      device requirements and verify the feasibility of continuous hemodynamic
      monitoring in CHF patients and devices for remote transfer and use of these data.
      METHODS AND RESULTS: The results of four separate studies in 68 CHF patients who
      received systems for chronic hemodynamic monitoring between 1992 and the present
      are reviewed. One early study was with five patients followed for 7-16 months and
      another study was with nine patients followed for 4-22 months. A third study
      included 21 patients followed up to 39 months, and the fourth study included 32
      patients implanted in 1998-99 with many of them still in follow-up. These studies
      support the technical feasibility of implanted devices and the external
      instrumentation required to transfer and manage the collected data. They also
      support the long-term stability and accuracy of these systems. Three additional
      acute studies conducted with 30 patients and chronic data from 53 of the 68
      patients with the implanted systems are presented that support the feature
      included in the newer monitors--the ability to reliably estimate pulmonary artery
      diastolic pressures from the right ventricular pressure signal. CONCLUSIONS:
      Development of implantable technology to measure several hemodynamic variables in
      ambulatory CHF patients is feasible. External instrumentation needed to remotely
      acquire data from the implanted devices has been verified. The potential to
      eliminate the uncertainties associated with the use of acute, invasive
      hemodynamics and the ability to evaluate long-term ambulatory hemodynamic
      patterns is provided. These findings set the stage for determining the potential
      clinical value of these systems in impacting the care of chronic CHF patients.

PMID- 15955194
TI  - Cross-ventricular pacemaker-mediated tachycardia by myopotential induction during
      biventricular pacing.
AB  - BACKGROUND: Patients in permanent atrial fibrillation treated for heart failure
      and ventricular asynchrony can be implanted with conventional dual chamber
      pacemakers (DDD) pacemakers used in the biventricular mode. The left ventricular
      lead is connected to the atrial channel. CASE REPORT: We report the case of a
      patient who developed ventriculo-ventricular pacemaker-mediated tachycardia (PMT)
      induced by myopotential sensing in the atrial channel, inhibiting left
      ventricular pacing. CONCLUSION: In the absence of specifically designed
      pacemakers, the use of DDD pacemakers in the biventricular mode requires certain
      precautions, such as anti-PMT mode activation, disabling automatic sensitivity,
      and lengthening the postventricular atrial refractory period (PVARP), or mode
      switch to DVIR.

PMID- 15955195
TI  - His-bundle pacing in a patient with persistent left superior vena cava.
AB  - The presence of a persistent left superior vena cava was encountered in a 53-year
      old woman undergoing a dual-chamber pacemaker implant for sick sinus syndrome.
      Active fixation leads were used and positioned in the right atrium and right
      ventricle via the left superior vena cava draining into the coronary sinus. The
      natural course of the right ventricular lead riding up the lateral atrial wall
      and curving backward toward the septum as it exits from the coronary sinus os was
      found to facilitate the positioning of the lead tip close to the His bundle
      without the use of a specially designed guiding catheter.

PMID- 15955196
TI  - Pregnancy in postural orthostatic tachycardia syndrome.
AB  - INTRODUCTION: Postural orthostatic tachycardia syndrome (POTS) is a rare disease
      characterized by syncope, sinus tachycardia, and orthostasis due to autonomic
      dysfunction. METHODS AND RESULTS: Two women aged 26 and 24 years with severe POTS
      became pregnant. Both women experienced hyperemesis gravidarum with subsequent
      marked improvement in their POTS symptoms until 6 months gestation, when their
      syncope and sinus tachycardia caused clinical decompensation. Both patients
      delivered healthy babies at 37 weeks by elective cesarean section. CONCLUSION: In
      long-term follow-up, both women reported improvement in their prepartum symptoms.
      We describe the first report, to our knowledge, of two successful pregnancy
      outcomes in severe POTS, including the first report of midodrine use in pregnant
      women.

PMID- 15955197
TI  - Radiofrequency catheter ablation therapy of swallowing-induced atrioventricular
      nodal reentrant tachycardia: report of two cases.
AB  - We describe two patients who presented with a history of recurrent palpitations
      on swallowing of solid food. The event-recorder and Holter monitoring documented
      episodic supraventricular tachycardia (SVT) initiated by atrial premature
      contractions (APCs). During electrophysiological study (EPS), swallowing of solid
      food consistently induced APCs and their activation sequence, morphology of P
      wave were suggestive of their right atrial origin in them. Drug challenge did not
      affect the APC onset during the swallowing. During EPS, slow-fast variety of
      atrioventricular nodal reentrant tachycardia (AVNRT) was induced and successful
      radiofrequency (RF) catheter ablation of slow pathway resulted in total relief of
      their symptoms.

PMID- 15955198
TI  - Right atrial tachycardia in a patient with severe atrial conduction disturbances
      and an anatomically normal heart.
AB  - We describe a case of abnormal right atrial (RA) conduction in a patient with
      atrial tachycardia (AT) but no history of structural heart disease or cardiac
      surgery. Following ablation of AT, the patient experienced typical atrial flutter
      (AFL) and a postcardioversion ECG suggestive of low atrial rhythm. Repeat EPS and
      three-dimensional electroanatomic activation mapping showed unusual RA activation
      during SR. This case illustrates the possibility that abnormal intraatrial
      conduction may lead to unusual patterns of activation in the RA which can serve
      as a necessary substrate for the initiation and maintenance of macro-reentry
      circuits.

PMID- 15955199
TI  - Supraventricular tachycardia with a baseline ECG pattern of Brugada syndrome.
AB  - The typical arrhythmias found in patients with the Brugada syndrome is either
      ventricular fibrillation or polymorphic ventricular tachycardia. We report the
      case of a patient who presented with supraventricular tachycardia accompanied by
      ECG features of the Brugada syndrome (BrS) during both tachyarrhythmia and sinus
      rhythm. This case lends support to the recently reported association between
      supraventricular tachyarrhythmia and BrS and the hypothesis that the
      arrhythmogenic substrate in BrS is not limited to the ventricular level.

PMID- 15955201
TI  - No correlation between atrial natriuretic concentration and echocardiographic
      measurements.

PMID- 15955202
TI  - Transcatheter arterial embolization for hemorrhage caused by injury of the
      hepatic artery.

PMID- 15955203
TI  - Factors influencing stem cell differentiation into the hepatic lineage in vitro.
AB  - A major area of research in transplantation medicine is the potential application
      of stem cells in liver regeneration. This would require well-defined and
      efficient protocols for directing the differentiation of stem cells into the
      hepatic lineage, followed by their selective purification and proliferation in
      vitro. The development of such protocols would reduce the likelihood of
      spontaneous differentiation of stem cells into divergent lineages upon
      transplantation, as well as reduce the risk of teratoma formation in the case of
      embryonic stem cells. Additionally, such protocols could provide useful in vitro
      models for studying hepatogenesis and liver metabolism. The development of
      pharmokinetic and cytotoxicity/genotoxicity screening tests for newly developed
      biomaterials and drugs, could also utilize protocols developed for the hepatic
      differentiation of stem cells. Hence, this review critically examines the various
      strategies that could be employed to direct the differentiation of stem cells
      into the hepatic lineage in vitro.

PMID- 15955204
TI  - Histone deacetylase inhibitors, anticancerous mechanism and therapy for
      gastrointestinal cancers.
AB  - Histone acetylation regulates gene transcription. Histone acetylation is a
      reversible process: histone acetyltransferases (HAT) transfer the acetyl moiety
      from acetyl coenzyme A to the lysine, and histone deacetylases (HDAC) remove the
      acetyl groups re-establishing the positive charge in the histones. HDAC
      inhibitors have antiproliferative activity against human cancer cells via cell
      cycle arrest, pro-differentiation, and pro-apoptosis. In recent years, many
      studies have shown that specific HDAC inhibitors are helpful for gastrointestinal
      cancer therapy.

PMID- 15955205
TI  - Changing prevalence of gastroesophageal reflux with changing time: longitudinal
      study in an Asian population.
AB  - BACKGROUND: The purpose of the present paper was to study previously obtained
      population-based data on the prevalence of reflux symptoms in a random sample of
      community adults in Singapore. This sample was re-investigated 5 years later to
      determine changes in the prevalence of reflux symptoms. METHODS: In 1999, 237
      (34%) of the original cohort of 696 persons who were interviewed in 1994, were re
      interviewed using a validated Gastrointestinal Symptoms Questionnaire. The
      original cohort was a race-stratified random sample of residents in a Singaporean
      town. Reflux was defined as heartburn and/or acid regurgitation occurring at
      least once a month. RESULTS: Among the 237 respondents (aged 25-89 years; male :
      female, 49:51; Chinese n = 106, 45%; Malay n = 69, 29%; Indian n = 60, 25%),
      reflux was reported by 25 respondents, giving a prevalence of 10.5 +/- 2.0%. This
      compared with the prevalence of 5.5 +/- 1.5% (odds ratio [OR], 2.2; 95%
      confidence interval [CI]: 1.0-5.2; P = 0.05) among the same 237 respondents in
      the 1994 survey. Of the 25 subjects who reported reflux in the current survey, 22
      (88.0%) did not complain of reflux symptoms in the 1994 survey. The ethnic
      adjusted prevalence of reflux in 1999 was estimated to be 9.9 +/- 1.9%. This was
      an increase above the prevalence in 1994 of 1.6 +/- 1.0% (P = 0.051). The upward
      trend in the prevalence of reflux was not related to age, smoking, alcohol
      consumption, or increase in bodyweight. CONCLUSIONS: There is a rising trend of
      reflux symptoms frequency in the general population of Singapore over a 5-year
      period.

PMID- 15955206
TI  - Enteral nutrition via percutaneous endoscopic gastrostomy and nutritional status
      of patients: five-year prospective study.
AB  - BACKGROUND: Since it was described in 1980, percutaneous endoscopic gastrostomy
      (PEG) has been a widely used method for insertion of a gastrostomy tube in
      patients who are unable to swallow or maintain adequate nutrition. The aim of the
      present paper was to determine the complications of PEG insertion and to study
      pre- and post-procedural nutritional status. METHODS: During the period of March
      1999-September 2004, placement of PEG tube was performed in 85 patients (22 women
      and 63 men). Patient nutritional status was assessed before and after PEG
      insertion via anthropometric measurements. RESULTS: The most frequent indication
      for PEG insertion was neurological disorders (65.9%). Thirty patients died due to
      primary disease and two patients due to PEG-related complications within 5 years.
      There were 14 early complications in 10 patients (15.2%; <30 days), and 18 late
      complications in 12 patients (19.6%). Total mortality was 37.6%. All
      complications other than four were minor. Before PEG insertion, patients were
      assessed with subjective global assessment and it was determined that 43.2% of
      them had severe, and 41.9% of them had mild malnutrition. After PEG insertion,
      significant improvements on patient nutrition levels was observed. CONCLUSION:
      Percutaneous endoscopic gastrostomy is a minimally invasive gastrostomy method
      with low morbidity and mortality rates, is easy to follow up and easy to replace
      when clogged.

PMID- 15955207
TI  - Duodenal ulcer in South Africa: home-pounded versus milled maize.
AB  - BACKGROUND: In South Africa there is suggestive evidence that home-pounded maize
      protects against duodenal ulceration. Therefore the purpose of the present paper
      was to test, in an animal model, whether oil from home-pounded maize gives
      protection against ulceration and whether this effect is present in commercially
      prepared maize oil. METHODS: Gastric ulceration was induced in rats with topical
      ethanol 1 h after giving oil prepared either from fresh-pounded or from
      commercially treated maize. The lengths of the linear ulcers produced were
      measured with a planimeter and summed in each rat. Control observations were made
      using arachis oil (which is known not to be ulceroprotective) and horse gram
      lipid (which is known to be strongly ulceroprotective). Statistical comparisons
      were performed mainly with the Mann-Whitney U-test, but also with reference to
      the normal distribution. Thin-layer chromatography (TLC) was performed on the oil
      from fresh maize, and the fractions similarly investigated for ulceroprotective
      activity. RESULTS: Fresh maize oil was strongly ulceroprotective (P = 0.0039),
      commercial maize oil was not (P = 0.2864). The active ingredient in the fresh
      maize oil was located in the fraction near the solvent front. CONCLUSION: These
      findings support the hypothesis that home-pounded maize protects against duodenal
      ulceration.

PMID- 15955208
TI  - Comparative study of the speed of acid-suppressing effects of oral administration
      of cimetidine and famotidine.
AB  - BACKGROUND AND AIM: H2 histamine receptor antagonists (H2RAs) are widely used in
      patients with acid-related diseases, and the onset of antisecretory activity of
      H2RAs is reported to be faster than that of proton pump inhibitors (PPIs). The
      aim of this study was to compare the rapidity of onset of antisecretory activity
      of cimetidine and famotidine when orally administered. METHODS: Fifteen healthy
      male Japanese volunteers (five H. pylori-positive and 10 H. pylori-negative)
      participated in a randomized cross-over study. All subjects were examined three
      times by ambulatory 6-h pH monitoring (from 17:30 to 23:30) with no medication or
      oral administration of 400 mg of cimetidine or 20 mg of famotidine. Drugs were
      administered at 19:30 after eating a standard meal, and plasma concentrations
      were also examined for 4 h periods. RESULTS: The plasma concentration of
      cimetidine increased rapidly after oral administration, while that of famotidine
      increased gradually. Intragastric pH was increased and percentage time with pH <
      4.0 decreased significantly 2 h after administration of either cimetidine or
      famotidine. There was no statistically significant difference in acid-suppressing
      effect between cimetidine and famotidine during the short-term post
      administration period. CONCLUSION: Rapidity of antisecretory activity did not
      differ between oral cimetidine and famotidine administered orally.

PMID- 15955209
TI  - Sulfasalazine inhibits activation of nuclear factor-kappaB in patients with
      ulcerative colitis.
AB  - BACKGROUND: Although sulfasalazine is widely used to treat inflammatory bowel
      disease, its mechanisms of action remain unclear. Activation of transcription
      factor nuclear factor (NF)-kappaB, which controls transcription of various pro
      inflammatory cytokine genes, has been shown to play a critical role in the
      pathogenesis of inflammatory bowel disease. The purpose of the present study was
      to determine whether sulfasalazine therapy affected NF-kappaB activation and the
      expression of pro-inflammatory cytokines in patients with ulcerative colitis.
      METHODS: A total of 38 patients with moderate ulcerative colitis were
      investigated. Twenty-one patients received sulfasalazine. Seventeen patients did
      not receive any medication. Biopsy specimens were obtained from inflamed mucosa
      and analyzed for NF-kappaB DNA binding activity, NF-kappaBp65/IkappaBalpha
      protein expression and the levels of pro-inflammatory cytokine mRNA using
      electrophoretic mobility shift assay, western blot analysis, immunohistochemical
      staining and reverse transcription-polymerase chain reaction (RT-PCR) analysis,
      respectively. RESULTS: Increased activation of NF-kappaB and high levels of the
      expression of interleukin (IL)-1beta mRNA and IL-8 mRNA were detected in biopsy
      specimens from patients with ulcerative colitis. Therapeutic administration of
      sulfasalazine effectively downregulated the activation of NF-kappaB and the
      expression of IL-1beta mRNA and IL-8 mRNA while IkappaBalpha levels were stable.
      CONCLUSION: The therapeutic benefits for ulcerative colitis of sulfasalazine
      might at least in part be attributed to its ability to inhibit NF-kappaB
      activation, resulting in the downregulation of pro-inflammatory cytokine mRNA
      expression.

PMID- 15955210
TI  - Prehepatic portal hypertension produces increased mast cell density in the small
      bowel and in mesenteric lymph nodes in the rat.
AB  - BACKGROUND: Because most of the characteristics of the portal hypertensive
      enteropathy can be explained on the basis of increased levels of mast cell
      mediators, the purpose of the present paper was to study mast cell splanchnic
      infiltration. METHODS: Duodenum, jejunum, ileum and mesenteric lymph node complex
      infiltration by mast cells was assayed by a stereological technique in control
      rats (group I; n = 5) and in an experimental model of portal hypertension (the
      portal vein-stenosed rat, group II; n = 5) at 6 weeks after operation. RESULTS:
      Intestinal and mesenteric lymph node complex infiltration by mast cells increased
      in the animals with partial portal vein ligation. The mast cell density
      progressively increased distally along the small bowel. The mast cell increase in
      the mesenteric lymph node complex in portal vein-stenosed rats was greater than
      in the duodenum (P = 0.001), jejunum (P = 0.006) and ileum. CONCLUSION: The rise
      of mast cells density in the small bowel and mesenteric lymph node complex in
      rats with partial portal vein ligation suggests that these cells are involved in
      the etiopathogenesis of experimental portal prehepatic hypertensive enteropathy.

PMID- 15955211
TI  - Ketotifen abrogates local and systemic consequences of rat intestinal ischemia
      reperfusion injury.
AB  - BACKGROUND: Mast cell-derived vasoactive and pro-inflammatory mediators,
      particularly histamine, might contribute to local tissue damage and multiorgan
      dysfunction induced by intestinal ischemia/reperfusion (I/R). The purpose of the
      present study was to evaluate the effects of the mast cell stabilizer, ketotifen,
      on leukocyte adhesion within, and tissue leakage from the mucosal villous
      microcirculation after intestinal I/R. METHODS: Superior mesenteric arteries of
      untreated and ketotifen-pretreated (1 mg/kg orally twice daily for 3 days, and 90
      min prior to ischemia) Piebald-Viral-Glaxo (PVG) rats were clamped for 30 min (n
      = 12 per group; sham operated controls n = 12). Mucosal surfaces of exteriorized
      ileal segments were visualized, and leukocyte adherence in, and macromolecular
      leakage (MML) from individual villi were followed for 2 h after clamp removal
      using in vivo microscopy. Blood pressure and heart rate were monitored, and lung
      tissue damage was assessed by histology. RESULTS: Ten untreated animals subjected
      to intestinal I/R failed to survive the reperfusion period, leukocyte adhesion (P
      < 0.001) and MML (P < 0.001) were increased at all time-points and blood flow
      stasis eventually ensued. In contrast, all ketotifen-pretreated I/R animals
      survived the duration of the study. Ketotifen abrogated I/R-induced leukocyte
      adherence within the villus mucosal capillaries and supplying arterioles and
      largely prevented pulmonary injury, yet surprisingly had no effect on intestinal
      vascular leakage. CONCLUSIONS: This is the first study to demonstrate that
      ketotifen is a powerful inhibitor of I/R-induced leukocyte adhesion and can
      prevent localized and reduce remote organ damage after intestinal I/R injury.
      However, its effects are manifested in the absence of any influence on intestinal
      I/R-induced vascular leakage.

PMID- 15955212
TI  - Expression of Ep-CAM in intestinal metaplasia, gastric epithelial dysplasia and
      gastric adenocarcinoma.
AB  - BACKGROUND: The epithelial cell adhesion molecule (Ep-CAM) is widely associated
      with human carcinomas. However, the expression and distribution of Ep-CAM in
      gastric premalignant and malignant lesions are not well known. METHOD: We
      examined the expression of Ep-CAM in 99 cases of gastric adenocarcinoma and
      associated uninvolved gastric mucosa, 39 cases of gastric biopsy specimens with
      chronic gastritis (CG) with or without intestinal metaplasia (IM) (25 cases) and
      gastric epithelial dysplasia (GED) (14 cases) by immunohistochemical staining. In
      gastric adenocarcinoma, we correlated the results with established prognostic
      factors, and in IM and GED, with Hepatocyte paraffin 1 (Hep Par 1) expression,
      introduced as a marker of IM. RESULTS: Ep-CAM overexpression was noted in 0% of
      normal epithelia, 93.9% of IM, 42.9% of GED and 34.3% of adenocarcinoma. The
      average immunostaining score of normal epithelia, IM, GED and gastric
      adenocarcinoma was 0.14 (+/- 0.26), 7.18 (+/- 1.93), 5.67 (+/- 2.29) and 4.09 (+/
      1.89), respectively. There were significant differences among the groups. Ep-CAM
      overexpression in adenocarcinoma correlated with Lauren classification and
      histologic grade, but not with tumor stage, lymph node metastasis and p53
      expression. Both Ep-CAM and Hep Par 1 expressions showed excellent correlations
      with IM (P < 0.0001). Ep-CAM expression was consistently observed in all cases of
      GED with a moderate to strong intensity, and Hep Par 1 weakly in 10 out of 14
      cases. CONCLUSION: Our findings suggest that increased levels of Ep-CAM represent
      an early event in gastric carcinogenesis, and seem to have a specific relation
      with the development of IM as a morphoregulatory molecule.

PMID- 15955213
TI  - Neutral lipid isolated from endosperm of Job's tears inhibits the growth of
      pancreatic cancer cells via apoptosis, G2/M arrest, and regulation of gene
      expression.
AB  - BACKGROUND: The neutral lipid isolated from the endosperm of Job's tears (NLEJ)
      has been known to possess an anticancer activity with relatively low toxicity.
      The present study was designed to examine its antiproliferative effects in the
      PaTu-8988 and SW1990 human pancreatic cancer cells and to investigate its
      potential mechanism(s). METHODS: Pancreatic cancer cells were treated with NLEJ
      to evaluate cell viability, cell cycle progression, nuclear morphology, DNA
      fragmentation and annexin V binding analysis. Regulation of gene expression was
      determined by using cDNA microarrays and western immunoblotting. RESULTS: The
      NLEJ induced a dose- and time-dependent inhibition of proliferation in both PaTu
      8988 and SW1990 cell lines. Further studies were carried out with only the PaTu
      8988 cells. Flow cytometry analysis showed that NLEJ blocked cell cycle
      progression at the G(2)/M phase. There was also an increase in annexin V binding
      and DNA fragmentation, indicative of apoptosis. The cDNA microarray analysis with
      cell cycle- and apoptosis-targeted arrays showed that the expression signals of
      24 genes were found to be significantly altered at 24 h of NLEJ treatment. These
      genes are involved in cell cycle control (e.g. p21, p27, CDK2, and cyclins),
      apoptosis regulation (e.g. bcl-2 and bax), and signal transduction (e.g. ATM,
      RAD50, and p53). Some of these results were confirmed by western blot analysis.
      CONCLUSIONS: These data show that NLEJ inhibits pancreatic cancer cell growth
      through induction of apoptosis and cell cycle arrest as well as regulation of
      gene expression in vitro. Therefore, NLEJ might be a chemotherapeutic agent
      against pancreatic cancer.

PMID- 15955214
TI  - Pilot study using transcutaneous electrical stimulation (interferential current)
      to treat chronic treatment-resistant constipation and soiling in children.
AB  - BACKGROUND: Chronic constipation in children may have organic or behavioral
      causes. The purpose of the present study was to investigate the effect of
      treatment with transcutaneous electrical stimulation (using interferential
      current) in children with chronic treatment-resistant constipation with proven
      organic disorders. METHODS: Eight children (7-16 years) with at least 4 years of
      chronic treatment-resistant constipation and soiling, who had failed diet,
      laxative treatment and behavioral therapy were given 1 month of transcutaneous
      electrical stimulation. The three most severe cases had appendicostomies with
      antegrade washouts every 2-3 days to prevent impaction and reduce their soiling.
      Children and carers kept a daily diary of bowel habits, recording number of
      spontaneous defecations, episodes of soiling, use of bowel washouts and
      medications. Transcutaneous stimulation using interferential current was applied
      three times per week for 3-4 weeks using four surface electrodes, two to the
      paraspinal area of T9-10 to L2 and one to either side of the anterior abdominal
      wall beneath the costal margin. Diaries were recorded for 1 month before, during,
      and after stimulation and for 2 weeks 3 months later. RESULTS: Transcutaneous
      electrical stimulation using interferential current stopped soiling in 7/8
      children and increased the frequency of spontaneous defecations in 5/8.
      Defecations remained high and soiling low for 3 months in 3/6 children (with
      data). CONCLUSIONS: These results suggest that transcutaneous electrical
      stimulation using interferential current has a beneficial effect for children
      with chronic treatment-resistant constipation. Further trials using larger series
      of patients are needed to confirm this benefit, to determine the ideal
      stimulation parameters and to investigate why electrical stimulation might be
      effective.

PMID- 15955215
TI  - Transcatheter arterial embolization for hemorrhage caused by injury of the
      hepatic artery.
AB  - BACKGROUND: The aims of the study were to compare (i) the effects of
      transcatheter arterial embolization on initial hemostasis and the control of
      rebleeding in the treatment of hemorrhage due to hepatic artery injury; and (ii)
      the outcomes of embolization by different locations. METHODS: Subjects were 32
      patients with suspected hepatic artery injury who were transferred to Chi-Mei
      Foundation Medical Center for hepatic angiography and embolization. The causes of
      arterial injury included liver trauma (n = 15) and iatrogenic injury (n = 17).
      The sites of embolization were classified into four groups: group 1 (n = 8) was
      classified as 'combined outlet, target and inlet control' with embolization of
      the vascular lesion (target) and hepatic artery distal (outlet) and proximal
      (inlet) to the vascular lesion simultaneously; group 2 (n = 11) as 'combined
      target and inlet control'; group 3 (n = 8) as 'combined outlet and inlet
      control'; group 4 (n = 5) as 'inlet control' only. RESULTS: Successful initial
      hemostasis was achieved in 30 of the 32 patients (93.8%), with two failures, both
      of which were caused by liver injury and occurred in subjects in group 4.
      Rebleeding was seen in three patients who had successful initial hemostasis: two
      of them in group 4 (66.7%) and one in group 1 (12.5%). All rebleedings were
      successfully managed by repeat embolization. Abscess formation was found in two
      group 1 patients, and both were successfully managed by percutaneous drainage.
      CONCLUSIONS: Transcatheter arterial embolization is an effective method for
      hemostasis in hepatic artery hemorrhage for both patients with liver trauma and
      patients with iatrogenic injuries to the hepatic artery. Based on this
      experience, embolization of the vascular lesion and/or the arterial lumen distal
      to the vascular lesion combined with inlet control is recommended for preventing
      recurrent hemorrhage, but studies with larger sample sizes will be required to
      validate this conclusion.

PMID- 15955216
TI  - Biliary excretion of taurocholate, organic anions and vinblastine in rats with
      alpha-naphthylisothiocyanate-induced cholestasis.
AB  - BACKGROUND AND AIMS: alpha-Naphthylisothiocyanate (ANIT) is known to cause
      cholestasis due to injury of the bile duct epithelial cells. The aim of the
      present study was to examine the effect of a single dose of ANIT on the biliary
      excretion of various cholephilic compounds and on the amount of canalicular
      transporters. METHODS: Twenty-four hours after the oral administration of ANIT
      (100 mg/kg), the biliary excretion of taurocholate, leukotriene C(4), pravastatin
      and vinblastine was studied. The protein levels of the bile salt export pump and
      multidrug resistance protein 2 and the immunostaining of multidrug resistance
      protein 2 in the liver were also examined. RESULTS: The ANIT treatment markedly
      decreased the biliary excretion of tracer amounts of taurocholate, leukotriene
      C(4), pravastatin and vinblastine. The biliary excretory maximum of taurocholate
      was also markedly decreased after ANIT treatment. The ANIT treatment had no
      effect on the protein levels of bile salt export pump and multidrug resistance
      protein 2 and the immunostaining of multidrug resistance protein 2 in the liver.
      CONCLUSIONS: These findings support canalicular transporters having little effect
      on the marked impairment of biliary excretion of cholephilic compounds in ANIT
      induced cholestasis.

PMID- 15955217
TI  - Effects of somatostatin, terlipressin and somatostatin plus terlipressin on
      portal and systemic hemodynamics and renal sodium excretion in patients with
      cirrhosis.
AB  - BACKGROUND AND AIM: Terlipressin and somatostatin are the most preferable agents
      for the control of variceal bleeding in cirrhotic patients. The present study
      evaluated the hemodynamic effects of somatostatin, terlipressin and somatostatin
      plus terlipressin in cirrhotic patients with portal hypertension, as well as the
      effect of each regimen on renal sodium excretion. METHODS: Twenty-four patients
      with esophageal varices were randomly assigned to receive either an intravenous
      infusion of a placebo (n = 12) or somatostatin 250 microg/h after an initial
      bolus of 250 microg (n = 12) for 60 min. Thereafter, each patient received an
      intravenous injection of terlipressin 2 mg while the intravenous infusion of
      either somatostatin or placebo was maintained. Portal and systemic hemodynamic
      parameters, assessed by Doppler sonography, and urinary sodium excretion were
      evaluated at baseline, 60 min after placebo or somatostatin, and 30 min after
      terlipressin. RESULTS: Placebo had no effect on the patients studied. After
      terlipressin, portal vein velocity, portal flow volume and cardiac output (CO)
      significantly decreased (0.09 vs 0.15 m/s, 0.56 vs 1 L/min and 6.4 vs 7.6 L/min,
      respectively [values are medians]), while mean arterial pressure (MAP) and
      systemic vascular resistance significantly increased (103.3 vs 89.9 mmHg and 1541
      vs 1108dyn.s/cm(5), respectively). Fractional sodium excretion significantly
      increased in patients without ascites (0.43 vs 0.16%) while it did not change in
      patients with ascites. Somatostatin did not alter portal hemodynamics whereas it
      significantly reduced MAP, heart rate (HR) and CO (86.9 vs 98.6 mmHg, 65 vs 73
      bpm and 8.4 vs 9.1 L/min, respectively) and, in patients with ascites, sodium
      excretion (0.13 vs 0.23%). The addition of terlipressin to somatostatin induced
      similar changes to those observed after terlipressin alone. The magnitude of
      increase in MAP was significantly higher in patients receiving terlipressin alone
      than in those receiving somatostatin plus terlipressin (15 vs 5.3%), while CO was
      conversely affected (-28.5 vs-20.9%). CONCLUSIONS: Combined treatment with
      somatostatin and terlipressin does not exert an additive portal hypotensive
      effect in cirrhotic patients as compared to terlipressin alone, whereas
      somatostatin alone may impair systemic hemodynamics. Compared with somatostatin,
      terlipressin exerts a more beneficial effect on renal sodium excretion in
      patients with or without ascites.

PMID- 15955218
TI  - Hepatitis C virus prevalence and outcomes among injecting drug users on opioid
      replacement therapy.
AB  - OBJECTIVES: To determine hepatitis C virus (HCV) prevalence among injecting drug
      users (IDUs) receiving opioid replacement therapy in a referred office setting,
      and assess potential needs for hepatitis C treatment and care. METHODS: Data were
      collected on 178 IDUs receiving opioid replacement therapy who underwent clinical
      assessment between January 2002 and June 2003. Standard clinic protocols included
      HCV and hepatitis B virus (HBV) serology, liver biochemistry and HCV RNA analysis
      for patients with a positive HCV antibody and normal alanine aminotransferase
      (ALT) levels. RESULTS: HCV prevalence was 75.3%, similar for males (75.5%) and
      females (74.4%), and increased with age from 60.8% for 19-30 years to 93.9% above
      40 years. Among patients with HCV antibodies and no prior HCV antiviral therapy
      (n = 130), 53.1% had normal ALT levels and 25.4% were HCV-RNA negative. Older
      patients were more likely to have normal ALT levels (P = 0.02), and be HCV-RNA
      negative (P = 0.02). Younger patients were more likely to have been HBV
      vaccinated (P < 0.001), however, were less likely to have either vaccine or
      natural immunity (P = 0.006). Of 97 patients with probable chronic HCV infection,
      58 patients met pre-liver biopsy criteria for HCV treatment, 34 had relative
      contraindications to treatment and 6 had been referred for treatment assessment.
      CONCLUSION: Clinical characterization in a setting of high HCV prevalence has
      enabled the differentiation of patients into groups with no evidence of HCV
      viraemia, with chronic HCV infection, and those most appropriate for HCV
      treatment referral. These clinical assessments along with appropriate referral
      should be instituted in drug dependency treatment settings.

PMID- 15955219
TI  - Outbreak of hepatitis C virus infection in an outpatient clinic.
AB  - BACKGROUND: From January through September 2001, seven patients were admitted to
      Fukaya Red Cross Hospital with typical clinical manifestations of acute
      hepatitis. Six were outpatients of the clinic, which is located near the
      hospital. An extensive survey of clinic outpatients conducted by the local health
      department revealed six more new acute hepatitis cases during this period.
      METHODS: A case control study was carried out to identify potential risk factors
      for infection. In total, 1946 outpatients with clinic records were scheduled to
      undergo hepatitis C virus (HCV)-antibody testing. For the HCV-Ab positive
      patients, HCV-RNA was subtyped and quantified, and sequences of HCV hypervariable
      region 1 were determined. RESULTS: Ultimately, 12 patients with acute hepatitis
      and two asymptomatic subjects were found to be a part of this outbreak. HCV
      isolates were divided into three major groups using phylogenetic tree analysis.
      Only a past history of visiting the clinic was significantly associated with
      acute hepatitis. The timing of the parenteral medical procedure at the clinic and
      the onset of acute hepatitis strongly suggested association of the two events.
      CONCLUSIONS: Our findings suggest that nosocomial HCV infection can occur in an
      outpatient clinic, even in countries where post-transfusion hepatitis has been
      almost entirely eliminated.

PMID- 15955220
TI  - Immunological alterations in pregnant women with acute hepatitis E.
AB  - BACKGROUND: Infection with hepatitis E virus (HEV) is a major cause of acute
      viral hepatitis in several developing countries. Although usually self-limiting
      and benign, the disease is particularly severe among pregnant women, with
      mortality rates reaching 15-20%. METHODS: Immune parameters among pregnant women
      with acute hepatitis E (P-HEV) were investigated and compared with those in non
      pregnant patients with hepatitis E (N-HEV), and healthy pregnant (PC) and non
      pregnant (NPC) women. RESULTS: Peripheral blood mononuclear cells (PBMC) from P
      HEV patients had lower lymphocyte proliferation response to phytohemagglutinin
      (PHA) than those in the PC and NPC groups. A positive lymphocyte proliferation
      response to HEV antigen (HEVAg), a mixture of eight peptides derived from HEV
      proteins, was observed in 7/19 (37%) P-HEV patients, 3/9 (33%) N-HEV patients and
      only 2/21 (10%) PC and 2/14 (14%) NPC subjects; the stimulation indices in the P
      HEV group were similar to the N-HEV group and higher than the PC group.
      Measurement of cytokine production by PBMC in response to PHA and HEVAg showed a
      reduction in production of T-helper 1 (Th1) cytokines and an increase in that of
      Th2 cytokines in the P-HEV group. Cytokine mRNA levels showed similar changes.
      CONCLUSION: These results show the existence of a Th2 bias in pregnant women with
      acute hepatitis E. The role of this Th2 bias in the greater severity of hepatitis
      E among pregnant women needs further investigation.

PMID- 15955221
TI  - Association of functional gene polymorphisms of matrix metalloproteinase (MMP)-1,
      MMP-3 and MMP-9 with the progression of chronic liver disease.
AB  - BACKGROUND AND AIMS: Matrix metalloproteinases (MMP) play an important role in
      the progression of liver fibrosis in addition to fibrogenesis. MMP-1, MMP-3, and
      MMP-9 gene polymorphisms have been shown to influence the transcriptional
      activity of their respective gene promoter in an allele-specific manner. The aim
      of this study was to examine the possible association of MMP-1, MMP-3, and MMP-9
      gene polymorphisms with the progression of chronic liver disease in the Japanese
      population. METHODS: We examined 91 patients with HCV-related chronic hepatitis
      and 89 patients with HCV-related liver cirrhosis. We determined MMP-1 1G/2G, MMP
      3 5A/6A, and MMP-9 C/T polymorphisms using polymerase-chain reaction based
      assays. RESULTS: In MMP-1 genotypes, the 2G homozygotes were significantly more
      in cirrhotic group than in chronic hepatitis group. In MMP-3 genotypes, there
      were no significant differences in genotype distributions and allele frequencies
      between chronic hepatitis and liver cirrhosis groups. However, 5A carriers had a
      significantly lower age at liver cirrhosis diagnosis and a higher Child-Pugh
      score compared with the 6A homozygotes. In MMP-9 genotypes, the C homozygotes and
      C allele frequencies were significantly more in liver cirrhosis group than in
      chronic hepatitis group. CONCLUSION: These findings suggest that MMP-1, MMP-3,
      and MMP-9 gene polymorphisms account for some of the variability in the
      progression of HCV-related chronic liver diseases.

PMID- 15955222
TI  - Hydroxyproline content of needle biopsies as an objective measure of liver
      fibrosis: Emphasis on sampling variability.
AB  - BACKGROUND: Needle liver biopsy is essential for the diagnosis of liver fibrosis
      and cirrhosis. However, sampling variability has been reported by
      semiquantitative methods. The aim of the present study was to investigate
      quantitatively the sampling variability of needle liver biopsy on the assessment
      of liver fibrosis/cirrhosis. METHODS: Liver samples of 12 patients undergoing
      autopsy, liver transplantation, or liver tumor resection were investigated. Nine
      to 10 liver biopsies at least 5 mm apart were taken from each of 12 removed human
      livers using Trucut needles. Hydroxyproline level of each liver core was
      determined. Sections >1 cm(2) and stained by Sirius red were used for the
      reference staging of liver fibrosis in each patient according to the METAVIR
      scoring system. RESULTS: Hydroxyproline levels for the three groups, F0-1, F2-3,
      and F4, were significantly elevated as the fibrosis score increased. There was a
      wide range of hydroxyproline contents for the 9-10 biopsy samples from each
      liver, the coefficient of variation being between 13% and 36% (mean, 23%).
      Several differences were noted between the amount of collagen present according
      to hydroxyproline measurement and the stages of fibrosis according to histology.
      CONCLUSIONS: Although increases in collagen content (by hydroxyproline)
      approximately paralleled increases in fibrosis stage (by histology), there was
      considerable overlap and some discrepancies. Much work remains to be done to
      clarify the significance of the apparent huge variations in fibrosis within
      diseased livers. It is advisable for clinicians to interpret staging diagnoses by
      histological staging with some caution.

PMID- 15955223
TI  - Brain natriuretic peptide and severity of disease in non-alcoholic cirrhotic
      patients.
AB  - BACKGROUND: Cirrhotic patients have a hyperdynamic systemic circulation. They
      have insidious cardiac problems besides well-known complications. Brain
      natriuretic peptide (BNP) relaxes vascular smooth muscle and has a portal
      hypotensive action. The relations between BNP levels and severity of disease,
      cardiac dysfunction and esophageal varices were studied in non-alcoholic
      cirrhotic patients. METHODS: Fifty-two non-alcoholic cirrhotic patients were
      evaluated for decompensation component of cirrhosis. The BNP concentration of
      echocardiographically examined patients was determined. RESULTS: The BNP levels
      were significantly higher in ascites, spontaneous bacterial peritonitis and
      hepatic encephalopathy history group (P = 0.033, P < 0.001, P = 0.014,
      respectively), but no significant difference were observed for presence of
      esophageal varices and bleeding history (P = 0.267, P = 0.429). A significant
      correlation was observed between BNP concentration and Child score (r = 0.427, P
      = 0.012), interventricular septal thickness (r = 0.497, P < 0.001) and left
      ventricular posterior wall thickness (r = 0.526, P < 0.001). According to Child
      Pugh classification there were no significant difference between groups for
      echocardiographic measurements and blood pressure (P > 0.05), but plasma BNP
      levels were significantly higher in Child class B and C patients compared with
      class A patients (P < 0.05). CONCLUSION: Increased levels of BNP are more likely
      related to the severity of disease in non-alcoholic cirrhotic patients. The
      advanced cirrhosis is associated with more advanced cardiac dysfunction and BNP
      has prognostic value in progression of cirrhosis.

PMID- 15955224
TI  - Images of interest. Gastrointestinal: acute gastric anisakiasis.

PMID- 15955225
TI  - Images of interest. Gastrointestinal: early endoscopic findings in watermelon
      stomach identified by the magnifying endoscopy-adaptive IHb color enhancement
      technique.

PMID- 15955226
TI  - Images of interest. Gastrointestinal: inflammatory myoglandular polyp of the
      colon.

PMID- 15955227
TI  - Images of interest. Hepatobiliary and pancreatic: colonic manifestations of
      portal hypertension.

PMID- 15955228
TI  - Images of interest. Hepatobiliary and pancreatic: colonic obstruction and hepatic
      encephalopathy.

PMID- 15955229
TI  - Hepatic natural killer and natural killer T cells markedly decreased in two cases
      of drug-induced fulminant hepatic failure rescued by living donor liver
      transplantation.
AB  - The human liver contains significant numbers of innate immune cells, such as
      natural killer (NK) cells and natural killer T (NKT) cells, which express both T
      cell receptors and NK-cell receptors simultaneously. It has been suggested that
      the innate immune system plays a crucial role in the liver. In this report, the
      distribution of NK and NKT cells in the liver and peripheral blood of two
      patients with drug-induced fulminant hepatic failure (FHF) who had undergone
      living donor liver transplantation was examined. In both the liver and peripheral
      blood, the proportions of NK and NKT cells markedly decreased compared with those
      in healthy donors. It was also revealed that, unlike murine NKT cells, human
      CD56(+) T cells and CD57(+) T cells did not constitutively express CD28, which is
      one of the important costimulatory molecules on T cells. Additionally, the
      residual CD56(+) T cells and CD57(+) T cells in the patients expressed more CD28
      than in controls. This result suggests that NKT cells might be more activated in
      FHF. Although the accumulation of further cases is required, it is suggested that
      both NK and NKT cells might be involved in hepatic injury in FHF.

PMID- 15955230
TI  - Facial nerve palsy due to temporal bone metastasis from hepatocellular carcinoma.

PMID- 15955231
TI  - Flt3/Itd mutation is not associated with gastrointestinal stromal tumors (gists).

PMID- 15955232
TI  - Prospective analysis of German patients with hepatocellular carcinoma undergoing
      transcatheter arterial chemoembolization with or without prophylactic antibiotic
      therapy.

PMID- 15955233
TI  - Fibrolamellar carcinoma of the liver in a Japanese hepatitis B virus carrier.

PMID- 15955234
TI  - 'Fat burner' herb, usnic acid, induced acute hepatitis in a family.

PMID- 15955235
TI  - Computational optical biopsy.
AB  - Optical molecular imaging is based on fluorescence or bioluminescence, and
      hindered by photon scattering in the tissue, especially in patient studies. Here
      we propose a computational optical biopsy (COB) approach to localize and quantify
      a light source deep inside a subject. In contrast to existing optical biopsy
      techniques, our scheme is to collect optical signals directly from a region of
      interest along one or multiple biopsy paths in a subject, and then compute
      features of an underlying light source distribution. In this paper, we formulate
      this inverse problem in the framework of diffusion approximation, demonstrate the
      solution uniqueness properties in two representative configurations, and obtain
      analytic solutions for reconstruction of both optical properties and source
      parameters.

PMID- 15955236
TI  - Response shift and glycemic control in children with diabetes.
AB  - BACKGROUND: The purpose of this study was to investigate the scale recalibration
      construct of response shift and its relationship to glycemic control in children
      with diabetes. METHODS: At year 1, thirty-eight children with type 1 diabetes
      attending a diabetes summer camp participated. At baseline and post-camp they
      completed the Problem Areas in Diabetes (PAID) questionnaire. Post-camp, the PAID
      was also completed using the 'thentest' method, which requires a retrospective
      judgment about their baseline functioning. At year 2, fifteen of the original
      participants reported their HbA1c. RESULTS: PAID scores significantly decreased
      from baseline to post-camp. An even larger difference was found between thentest
      and post-camp scores, suggesting scale recalibration. There was a significant
      positive correlation between year 1 HbA1c and thentest scores. Partial
      correlation analysis between PAID thentest scores and year 2 HbA1c, controlling
      for year 1 HbA1c, showed that higher PAID thentest scores were associated with
      higher year 2 HbA1c. CONCLUSION: Results from this small sample suggest that
      children with diabetes do show scale recalibration, and that it may be related to
      glycemic control.

PMID- 15955237
TI  - Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide
      excision repair in breast tissue and blood lymphocytes.
AB  - BACKGROUND: Screening mammography has had a positive impact on breast cancer
      mortality but cannot detect all breast tumors. In a small study, we confirmed
      that low power magnetic resonance imaging (MRI) could identify mammographically
      undetectable tumors by applying it to a high risk population. Tumors detected by
      this new technology could have unique etiologies and/or presentations, and may
      represent an increasing proportion of clinical practice as new screening methods
      are validated and applied A very important aspect of this etiology is genomic
      instability, which is associated with the loss of activity of the breast cancer
      predisposing genes BRCA1 and BRCA2. In sporadic breast cancer, however, there is
      evidence for the involvement of a different pathway of DNA repair, nucleotide
      excision repair (NER), which remediates lesions that cause a distortion of the
      DNA helix, including DNA cross-links. CASE PRESENTATION: We describe a breast
      cancer patient with a mammographically undetectable stage I tumor identified in
      our MRI screening study. She was originally considered to be at high risk due to
      the familial occurrence of breast and other types of cancer, and after diagnosis
      was confirmed as a carrier of a Q1200X mutation in the BRCA1 gene. In vitro
      analysis of her normal breast tissue showed no differences in growth rate or
      differentiation potential from disease-free controls. Analysis of cultured blood
      lymphocyte and breast epithelial cell samples with the unscheduled DNA synthesis
      assay (UDS) revealed no deficiency in nucleotide excision repair (NER).
      CONCLUSION: As new breast cancer screening methods become available and cost
      effective, patients such as this one will constitute an increasing proportion of
      the incident population, so it is important to determine whether they differ from
      current patients in any clinically important ways. Despite her status as a BRCA1
      mutation carrier, and her mammographically dense breast tissue, we did not find
      increased cell proliferation or deficient differentiation potential in her breast
      epithelial cells, which might have contributed to her cancer susceptibility.
      Although NER deficiency has been demonstrated repeatedly in blood samples from
      sporadic breast cancer patients, analysis of blood cultured lymphocytes and
      breast epithelial cells for this patient proves definitively that heterozygosity
      for inactivation of BRCA1 does not intrinsically confer this type of genetic
      instability. These data suggest that the mechanism of genomic instability driving
      the carcinogenic process may be fundamentally different in hereditary and
      sporadic breast cancer, resulting in different genotoxic susceptibilities,
      oncogene mutations, and a different molecular pathogenesis.

PMID- 15955238
TI  - Evaluation of the similarity of gene expression data estimated with SAGE and
      Affymetrix GeneChips.
AB  - BACKGROUND: Serial Analysis of Gene Expression (SAGE) and microarrays have found
      a widespread application, but much ambiguity exists regarding the evaluation of
      these technologies. Cross-platform utilization of gene expression data from the
      SAGE and microarray technology could reduce the need for duplicate experiments
      and facilitate a more extensive exchange of data within the research community.
      This requires a measure for the correspondence of the different gene expression
      platforms. To date, a number of cross-platform evaluations (including a few
      studies using SAGE and Affymetrix GeneChips) have been conducted showing a
      variable, but overall low, concordance. This study evaluates these overall
      measures and introduces the between-ratio difference as a concordance measure
      pergene. RESULTS: In this study, gene expression measurements of Unigene clusters
      represented by both Affymetrix GeneChips HG-U133A and SAGE were compared using
      two independent RNA samples. After matching of the data sets the final comparison
      contains a small data set of 1094 unique Unigene clusters, which is unbiased with
      respect to expression level. Different overall correlation approaches, like
      Up/Down classification, contingency tables and correlation coefficients were used
      to compare both platforms. In addition, we introduce a novel approach to compare
      two platforms based on the calculation of differences between expression ratios
      observed in each platform for each individual transcript. This approach results
      in a concordance measure per gene (with statistical probability value), as
      opposed to the commonly used overall concordance measures between platforms.
      CONCLUSION: We can conclude that intra-platform correlations are generally good,
      but that overall agreement between the two platforms is modest. This might be due
      to the binomially distributed sampling variation in SAGE tag counts, SAGE
      annotation errors and the intensity variation between probe sets of a single gene
      in Affymetrix GeneChips. We cannot identify or advice which platform performs
      better since both have their (dis)-advantages. Therefore it is strongly
      recommended to perform follow-up studies of interesting genes using additional
      techniques. The newly introduced between-ratio difference is a filtering
      independent measure for between-platform concordance. Moreover, the between-ratio
      difference per gene can be used to detect transcripts with similar regulation on
      both platforms.

PMID- 15955239
TI  - A census of membrane-bound and intracellular signal transduction proteins in
      bacteria: bacterial IQ, extroverts and introverts.
AB  - BACKGROUND: Analysis of complete microbial genomes showed that intracellular
      parasites and other microorganisms that inhabit stable ecological niches encode
      relatively primitive signaling systems, whereas environmental microorganisms
      typically have sophisticated systems of environmental sensing and signal
      transduction. RESULTS: This paper presents results of a comprehensive census of
      signal transduction proteins--histidine kinases, methyl-accepting chemotaxis
      receptors, Ser/Thr/Tyr protein kinases, adenylate and diguanylate cyclases and c
      di-GMP phosphodiesterases--encoded in 167 bacterial and archaeal genomes,
      sequenced by the end of 2004. The data have been manually checked to avoid false
      negative and false-positive hits that commonly arise during large-scale automated
      analyses and compared against other available resources. The census data show
      uneven distribution of most signaling proteins among bacterial and archaeal
      phyla. The total number of signal transduction proteins grows approximately as a
      square of genome size. While histidine kinases are found in representatives of
      all phyla and are distributed according to the power law, other signal
      transducers are abundant in certain phylogenetic groups but virtually absent in
      others. CONCLUSION: The complexity of signaling systems differs even among
      closely related organisms. Still, it usually can be correlated with the
      phylogenetic position of the organism, its lifestyle, and typical environmental
      challenges it encounters. The number of encoded signal transducers (or their
      fraction in the total protein set) can be used as a measure of the organism's
      ability to adapt to diverse conditions, the 'bacterial IQ', while the ratio of
      transmembrane receptors to intracellular sensors can be used to define whether
      the organism is an 'extrovert', actively sensing the environmental parameters, or
      an 'introvert', more concerned about its internal homeostasis. Some of the
      microorganisms with the highest IQ, including the current leader Wolinella
      succinogenes, are found among the poorly studied beta-, delta- and epsilon
      proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true
      introverts, probably due to their capacity to conduct oxygenic photosynthesis,
      using a complex system of intracellular membranes. The census data, available at
      http://www.ncbi.nlm.nih.gov/Complete_Genomes/SignalCensus.html, can be used to
      get an insight into metabolic and behavioral propensities of each given organism
      and improve prediction of the organism's properties based solely on its genome
      sequence.

PMID- 15955240
TI  - Genome-wide structural and evolutionary analysis of the P450 monooxygenase genes
      (P450ome) in the white rot fungus Phanerochaete chrysosporium: evidence for gene
      duplications and extensive gene clustering.
AB  - BACKGROUND: Phanerochaete chrysosporium, the model white rot basidiomycetous
      fungus, has the extraordinary ability to mineralize (to CO2) lignin and detoxify
      a variety of chemical pollutants. Its cytochrome P450 monooxygenases have
      recently been implied in several of these biotransformations. Our initial P450
      cloning efforts in P. chrysosporium and its subsequent whole genome sequencing
      have revealed an extraordinary P450 repertoire ("P450ome") containing at least
      150 P450 genes with yet unknown function. In order to understand the functional
      diversity and the evolutionary mechanisms and significance of these hemeproteins,
      here we report a genome-wide structural and evolutionary analysis of the P450ome
      of this fungus. RESULTS: Our analysis showed that P. chrysosporium P450ome could
      be classified into 12 families and 23 sub-families and is characterized by the
      presence of multigene families. A genome-level structural analysis revealed 16
      organizationally homogeneous and heterogeneous clusters of tandem P450 genes.
      Analysis of our cloned cDNAs revealed structurally conserved characteristics
      (intron numbers and locations, and functional domains) among members of the two
      representative multigene P450 families CYP63 and CYP505 (P450foxy). Considering
      the unusually complex structural features of the P450 genes in this genome,
      including microexons (2-10 aa) and frequent small introns (45-55 bp), alternative
      splicing, as experimentally observed for CYP63, may be a more widespread event in
      the P450ome of this fungus. Clan-level phylogenetic comparison revealed that P.
      chrysosporium P450 families fall under 11 fungal clans and the majority of these
      multigene families appear to have evolved locally in this genome from their
      respective progenitor genes, as a result of extensive gene duplications and
      rearrangements. CONCLUSION: P. chrysosporium P450ome, the largest known to date
      among fungi, is characterized by tandem gene clusters and multigene families.
      This enormous P450 gene diversity has evolved by extensive gene duplications and
      intragenomic recombinations of the progenitor genes presumably to meet the
      exceptionally high metabolic demand of this biodegradative group of
      basidiomycetous fungi in ecological niches. In this context, alternative splicing
      appears to further contribute to the evolution of functional diversity of the
      P450ome in this fungus. The evolved P450 diversity is consistent with the known
      vast biotransformation potential of P. chrysosporium. The presented analysis will
      help design future P450 functional studies to understand the underlying
      mechanisms of secondary metabolism and oxidative biotransformation pathways in
      this model white rot fungus.

PMID- 15955241
TI  - Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial
      pneumonia.
AB  - BACKGROUND: Heat shock protein (HSP) 47, a collagen-specific molecular chaperone,
      is involved in the processing and/or secretion of procollagens, and its
      expression is increased in various fibrotic diseases. The aim of this study was
      to determine whether quantitative immunohistochemical evaluation of the
      expression levels of HSP47, type I procollagen and alpha-smooth muscle actin
      (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP)
      from UIP associated with collagen vascular disease (CVD) and idiopathic
      nonspecific interstitial pneumonia (NSIP). METHODS: We reviewed surgical lung
      biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP
      and 16 with idiopathic NSIP and assigned a score for the expression of HSP47,
      type I procollagen and alpha-SMA in type II pneumocytes and/or lung fibroblasts
      (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). RESULTS: The
      expression level of HSP47 in type II pneumocytes of idiopathic UIP was
      significantly higher than in CVD-associated UIP and idiopathic NSIP. The
      expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and
      idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen
      in type II pneumocytes was significantly higher in idiopathic UIP than in
      idiopathic NSIP. The expression of type I procollagen in fibroblasts was not
      different in the three groups, while the expression of alpha-SMA in fibroblasts
      was significantly higher in idiopathic UIP than in idiopathic NSIP. CONCLUSION:
      Our results suggest the existence of different fibrotic pathways among these
      groups involved in the expression of HSP47 and type I procollagen.

PMID- 15955242
TI  - A large left ventricular pseudoaneurysm in Behcet's disease: a case report.
AB  - BACKGROUND: Behcet's disease is a collagen-vascular disease most commonly seen in
      Asia and Mediterranean area. Different organs and systems including
      cardiovascular system could be involved. Pseudoaneurysm is the most common form
      of arterial involvement in Behcet's disease; however, cardiac pseudoaneurysm is
      rare. CASE PRESENTATION: A rare case of 13 years old boy with a 4-year history of
      Behcet's disease with development of a huge left ventricular pseudoaneurysm is
      reported who had been admitted because of cough, chills, fever, and chest pain.
      Findings obtained on echocardiography, magnetic resonance imaging, chest computed
      tomography and coronary angiography confirmed a left ventricular pseudoaneurysm.
      There was no complication for next 24 months follow up period after surgical
      treatment. CONCLUSION: Considering its fatality and nonspecific manifestations,
      one should consider cardiac pseudoaneurysms as a potential risk in any patient
      with Behcet's disease.

PMID- 15955243
TI  - High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by
      human immunodeficiency virus.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) infection is very prevalent in
      Brazil. HIV therapy has been recently associated with coronary heart disease
      (CHD). Dyslipidemia is a major risk factor for CHD that is frequently described
      in HIV positive patients, but very few studies have been conducted in Brazilian
      patients evaluating their lipid profiles. METHODS: In the present work, we
      evaluated the frequency and severity of dyslipidemia in 257 Brazilian HIV
      positive patients. Two hundred and thirty-eight (93%) were submitted to
      antiretroviral therapy (224 treated with protease inhibitors plus nucleoside
      reverse transcriptase inhibitors, 14 treated only with the latter, 12 naive and 7
      had no records of treatment). The average time on drug treatment with
      antiretroviral therapy was 20 months. None of the patients was under lipid
      lowering drugs. Cholesterol, triglyceride, phospholipid and free fatty acids were
      determined by enzymatic colorimetric methods. Lipoprotein profile was estimated
      by the Friedewald formula and Fredrickson's phenotyping was obtained by serum
      electrophoresis on agarose. Apolipoprotein B and AI and lipoprotein "a" were
      measured by nephelometry. RESULTS: The Fredrickson phenotypes were: type IIb
      (51%), IV (41%), IIa (7%). In addition one patient was type III and another type
      V. Thirty-three percent of all HIV+ patients presented serum cholesterol levels
      >or= 200 mg/dL, 61% LDL-cholesterol >or= 100 mg/dL, 65% HDL-cholesterol below 40
      mg/dL, 46% triglycerides >or= 150 mg/dL and 10% have all these parameters above
      the limits. Eighty-six percent of patients had cholesterol/HDL-cholesterol ratio
      >or= 3.5, 22% increased lipoprotein "a", 79% increased free fatty acids and 9%
      increased phospholipids. The treatment with protease inhibitors plus nucleoside
      reverse transcriptase inhibitors increased the levels of cholesterol and
      triglycerides in these patients when compared with naive patients. The HDL
      cholesterol (p = 0.01) and apolipoprotein A1 (p = 0.02) levels were inversely
      correlated with the time of protease inhibitor therapy while total cholesterol
      levels had a trend to correlate with antiretroviral therapy (p = 0.09).
      CONCLUSION: The highly varied and prevalent types of dyslipidemia found in
      Brazilian HIV positive patients on antiretroviral therapies indicate the urgent
      need for their early diagnosis, the identification of the risk factors for CHD
      and, when needed, the prompt intervention on their lifestyle and/or with drug
      treatment.

PMID- 15955245
TI  - A survey of training and practice patterns of massage therapists in two US
      states.
AB  - BACKGROUND: Despite the growing popularity of therapeutic massage in the US,
      little is known about the training or practice characteristics of massage
      therapists. The objective of this study was to describe these characteristics.
      METHODS: As part of a study of random samples of complementary and alternative
      medicine (CAM) practitioners, we interviewed 226 massage therapists licensed in
      Connecticut and Washington state by telephone in 1998 and 1999 (85% of those
      contacted) and then asked a sample of them to record information on 20
      consecutive visits to their practices (total of 2005 consecutive visits).
      RESULTS: Most massage therapists were women (85%), white (95%), and had completed
      some continuing education training (79% in Connecticut and 52% in Washington).
      They treated a limited number of conditions, most commonly musculoskeletal (59%
      and 63%) (especially back, neck, and shoulder problems), wellness care (20% and
      19%), and psychological complaints (9% and 6%) (especially anxiety and
      depression). Practitioners commonly used one or more assessment techniques (67%
      and 74%) and gave a massage emphasizing Swedish (81% and 77%), deep tissue (63%
      and 65%), and trigger/pressure point techniques (52% and 46%). Self-care
      recommendations, including increasing water intake, body awareness, and specific
      forms of movement, were made as part of more than 80% of visits. Although most
      patients self-referred to massage, more than one-quarter were receiving
      concomitant care for the same problem from a physician. Massage therapists rarely
      communicated with these physicians. CONCLUSION: This study provides new
      information about licensed massage therapists that should be useful to physicians
      and other healthcare providers interested in learning about massage therapy in
      order to advise their patients about this popular CAM therapy.

PMID- 15955246
TI  - Construction of a bacterial artificial chromosome library from the spikemoss
      Selaginella moellendorffii: a new resource for plant comparative genomics.
AB  - BACKGROUND: The lycophytes are an ancient lineage of vascular plants that
      diverged from the seed plant lineage about 400 Myr ago. Although the lycophytes
      occupy an important phylogenetic position for understanding the evolution of
      plants and their genomes, no genomic resources exist for this group of plants.
      RESULTS: Here we describe the construction of a large-insert bacterial artificial
      chromosome (BAC) library from the lycophyte Selaginella moellendorffii. Based on
      cell flow cytometry, this species has the smallest genome size among the
      different lycophytes tested, including Huperzia lucidula, Diphaiastrum digita,
      Isoetes engelmanii and S. kraussiana. The arrayed BAC library consists of 9126
      clones; the average insert size is estimated to be 122 kb. Inserts of chloroplast
      origin account for 2.3% of the clones. The BAC library contains an estimated ten
      genome-equivalents based on DNA hybridizations using five single-copy and two
      duplicated S. moellendorffii genes as probes. CONCLUSION: The S. moellenforffii
      BAC library, the first to be constructed from a lycophyte, will be useful to the
      scientific community as a resource for comparative plant genomics and evolution.

PMID- 15955247
TI  - Transforming growth factor beta-1 (TGFB1) and peak bone mass: association between
      intragenic polymorphisms and quantitative ultrasound of the heel.
AB  - BACKGROUND: Variance of peak bone mass has a substantial genetic component, as
      has been shown with twin studies examining quantitative measures such as bone
      mineral density (BMD) and quantitative ultrasound (QUS). Evidence implicating
      single nucleotide polymorphisms (SNPs) of the transforming growth factor beta-1
      (TGFB1) gene is steadily accumulating. However, a comprehensive look at multiple
      SNPs at this locus for their association with indices of peak bone mass has not
      been reported. METHODS: A cohort of 653 healthy Caucasian females 18 to 35 years
      old was genotyped for seven TGFB1 SNPs. Polymorphisms were detected by
      restriction endonuclease digestion of amplified DNA segments. RESULTS: The
      frequencies of the least common allele at G-800A, C-509T, codon 10 (L10P), codon
      25 (R25P), codon 263 (T263I), C861-20T, and 713-8 delC loci were 0.07, 0.33,
      0.41, 0.08, 0.04, 0.25 and 0.01, respectively. A significant association was seen
      between QUS Stiffness Index (QUS-SI) and the SNP at codon 10 and the linked
      promoter SNP, C-509T. This association remained significant after multiple
      regression was used to incorporate important clinical covariates--age, BMI, level
      of activity, family history, and caffeine intake--into the model. CONCLUSION: The
      association of QUS-SI with -509T is consistent with a gene-dose effect, while
      only individuals homozygous for the codon 10P allele showed a significant
      increase. In this cohort of young healthy Caucasian females, the T allele at
      position -509 is associated with greater bone mass as measured by calcaneal
      ultrasound.

PMID- 15955248
TI  - Application of direct agglutination test (DAT) and fast agglutination screening
      test (FAST) for sero-diagnosis of visceral leishmaniasis in endemic area of Minas
      Gerais, Brazil.
AB  - BACKGROUND: The direct agglutination test (DAT) has proved to be a very important
      sero-diagnostic tool combining high levels of intrinsic validity and ease of
      performance. Otherwise, fast agglutination screening test (FAST) utilises only
      one serum dilution making the test very suitable for the screening of large
      populations. RESULTS: We have tested FAST and DAT for the detection anti
      Leishmania antibodies in serum samples from patients with American visceral (AVL)
      and cutaneous leishmaniases (ACL) in Minas Gerais State, Brazil. The DAT on serum
      and blood samples of confirmed AVL patients found all samples positive at a serum
      dilution of > or = 1:800. This dilution was subsequently used as cut off value in
      the study. The blood and serum samples of these confirmed patients could also be
      clearly read in FAST using a 1:100 dilution with the same high sensitivity. DAT
      and FAST were not able to detect significant amounts of antibodies in samples
      from ACL patients and are not suitable for the diagnosis of this manifestation of
      the disease. CONCLUSION: We suggest that both DAT and FAST are very practical
      diagnostic tools for the sero-diagnosis of AVL under rural conditions as both
      serological tests do not require sophisticated equipment, a cold chain and are
      very simple to perform.

PMID- 15955249
TI  - Municipal health expectancy in Japan: decreased healthy longevity of older people
      in socioeconomically disadvantaged areas.
AB  - BACKGROUND: Little is known about small-area variation in healthy longevity of
      older people and its socioeconomic correlates. This study aimed to estimate
      health expectancy at 65 years (HE65) at the municipal level in Japan, and to
      examine its relation to area socio-demographic conditions. METHODS: HE65 of
      municipalities (N = 3361) across Japan was estimated by a linear regression
      formula with life expectancy at 65 years and the prevalence of those certificated
      as needing nursing care. The relation between HE65 and area socio-demographic
      indicators was examined using correlation coefficients. RESULTS: The estimated
      HE65 (years) ranged from 13.13 to 17.39 for men and from 14.84 to 20.53 for
      women. HE65 was significantly positively correlated with the proportion of
      elderly and per capita income, and negatively correlated with the percentage of
      households of a single elderly person, divorce rate, and unemployment rate. These
      relations were stronger in large municipalities (with a population of more than
      100,000) than in small and medium-size municipalities. CONCLUSION: A decrease in
      healthy longevity of older people was associated with a higher percentage of
      households of a single elderly person and divorce rate, and lower socioeconomic
      conditions. This study suggests that older people in urban areas are susceptible
      to socio-demographic factors, and a social support network for older people
      living in socioeconomically disadvantaged conditions should be encouraged.

PMID- 15955250
TI  - Evaluation of amplified rDNA restriction analysis (ARDRA) for the identification
      of Mycoplasma species.
AB  - BACKGROUND: Mycoplasmas are present worldwide in a large number of animal hosts.
      Due to their small genome and parasitic lifestyle, Mycoplasma spp. require
      complex isolation media. Nevertheless, already over 100 different species have
      been identified and characterized and their number increases as more hosts are
      sampled. We studied the applicability of amplified rDNA restriction analysis
      (ARDRA) for the identification of all 116 acknowledged Mycoplasma species and
      subspecies. METHODS: Based upon available 16S rDNA sequences, we calculated and
      compared theoretical ARDRA profiles. To check the validity of these theoretically
      calculated profiles, we performed ARDRA on 60 strains of 27 different species and
      subspecies of the genus Mycoplasma. RESULTS: In silico digestion with the
      restriction endonuclease AluI (AG--CT) was found to be most discriminative and
      generated from 3 to 13 fragments depending on the Mycoplasma species. Although 73
      Mycoplasma species could be differentiated using AluI, other species gave
      undistinguishable patterns. For these, an additional restriction digestion,
      typically with BfaI (C--TAG) or HpyF10VI (GCNNNNN--NNGC), was needed for a final
      identification. All in vitro obtained restriction profiles were in accordance
      with the calculated fragments based on only one 16S rDNA sequence, except for two
      isolates of M. columbinum and two isolates of the M. mycoides cluster, for which
      correct ARDRA profiles were only obtained if the sequences of both rrn operons
      were taken into account. CONCLUSION: Theoretically, restriction digestion of the
      amplified rDNA was found to enable differentiation of all described Mycoplasma
      species and this could be confirmed by application of ARDRA on a total of 27
      species and subspecies.

PMID- 15955251
TI  - The clinical course of acute otitis media in high-risk Australian Aboriginal
      children: a longitudinal study.
AB  - BACKGROUND: It is unclear why some children with acute otitis media (AOM) have
      poor outcomes. Our aim was to describe the clinical course of AOM and the
      associated bacterial nasopharyngeal colonisation in a high-risk population of
      Australian Aboriginal children. METHODS: We examined Aboriginal children younger
      than eight years who had a clinical diagnosis of AOM. Pneumatic otoscopy and
      video-otoscopy of the tympanic membrane (TM) and tympanometry was done every
      weekday if possible. We followed children for either two weeks (AOM without
      perforation), or three weeks (AOM with perforation), or for longer periods if the
      infection persisted. Nasopharyngeal swabs were taken at study entry and then
      weekly. RESULTS: We enrolled 31 children and conducted a total of 219
      assessments. Most children had bulging of the TM or recent middle ear discharge
      at diagnosis. Persistent signs of suppurative OM (without ear pain) were present
      in most children 7 days (23/30, 77%), and 14 days (20/26, 77%) later. Episodes of
      AOM did not usually have a sudden onset or short duration. Six of the 14 children
      with fresh discharge in their ear canal had an intact or functionally intact TM.
      Perforation size generally remained very small (<2% of the TM). Healing followed
      by re-perforation was common. Ninety-three nasophyngeal swabs were taken. Most
      swabs cultured Streptococcus pneumoniae (82%), Haemophilus influenzae (71%), and
      Moraxella catarrhalis (95%); 63% of swabs cultured all three pathogens.
      CONCLUSION: In this high-risk population, AOM was generally painless and
      persistent. These infections were associated with persistent bacterial
      colonisation of the nasopharynx and any benefits of antibiotics were modest at
      best. Systematic follow up with careful examination and review of treatment are
      required and clinical resolution cannot be assumed.

PMID- 15955252
TI  - Inhibition or knock out of inducible nitric oxide synthase result in resistance
      to bleomycin-induced lung injury.
AB  - BACKGROUND: In the present study, by comparing the responses in wild-type mice
      (WT) and mice lacking (KO) the inducible (or type 2) nitric oxide synthase
      (iNOS), we investigated the role played by iNOS in the development of on the lung
      injury caused by bleomycin administration. When compared to bleomycin-treated
      iNOSWT mice, iNOSKO mice, which had received bleomycin, exhibited a reduced
      degree of the (i) lost of body weight, (ii) mortality rate, (iii) infiltration of
      the lung with polymorphonuclear neutrophils (MPO activity), (iv) edema formation,
      (v) histological evidence of lung injury, (vi) lung collagen deposition and (vii)
      lung Transforming Growth Factor beta1 (TGF-beta1) expression. METHODS: Mice
      subjected to intratracheal administration of bleomycin developed a significant
      lung injury. Immunohistochemical analysis for nitrotyrosine revealed a positive
      staining in lungs from bleomycin-treated iNOSWT mice. RESULTS: The intensity and
      degree of nitrotyrosine staining was markedly reduced in tissue section from
      bleomycin-iNOSKO mice. Treatment of iNOSWT mice with of GW274150, a novel, potent
      and selective inhibitor of iNOS activity (5 mg/kg i.p.) also significantly
      attenuated all of the above indicators of lung damage and inflammation.
      CONCLUSION: Taken together, our results clearly demonstrate that iNOS plays an
      important role in the lung injury induced by bleomycin in the mice.

PMID- 15955253
TI  - Spatial analysis of lung, colorectal, and breast cancer on Cape Cod: an
      application of generalized additive models to case-control data.
AB  - BACKGROUND: The availability of geographic information from cancer and birth
      defect registries has increased public demands for investigation of perceived
      disease clusters. Many neighborhood-level cluster investigations are
      methodologically problematic, while maps made from registry data often ignore
      latency and many known risk factors. Population-based case-control and cohort
      studies provide a stronger foundation for spatial epidemiology because potential
      confounders and disease latency can be addressed. METHODS: We investigated the
      association between residence and colorectal, lung, and breast cancer on upper
      Cape Cod, Massachusetts (USA) using extensive data on covariates and residential
      history from two case-control studies for 1983-1993. We generated maps using
      generalized additive models, smoothing on longitude and latitude while adjusting
      for covariates. The resulting continuous surface estimates disease rates relative
      to the whole study area. We used permutation tests to examine the overall
      importance of location in the model and identify areas of increased and decreased
      risk. RESULTS: Maps of colorectal cancer were relatively flat. Assuming 15 years
      of latency, lung cancer was significantly elevated just northeast of the
      Massachusetts Military Reservation, although the result did not hold when we
      restricted to residences of longest duration. Earlier non-spatial epidemiology
      had found a weak association between lung cancer and proximity to gun and mortar
      positions on the reservation. Breast cancer hot spots tended to increase in
      magnitude as we increased latency and adjusted for covariates, indicating that
      confounders were partly hiding these areas. Significant breast cancer hot spots
      were located near known groundwater plumes and the Massachusetts Military
      Reservation. DISCUSSION: Spatial epidemiology of population-based case-control
      studies addresses many methodological criticisms of cluster studies and generates
      new exposure hypotheses. Our results provide evidence for spatial clustering of
      breast cancer on upper Cape Cod. The analysis suggests further investigation of
      the potential association between breast cancer and pollution plumes based on
      detailed exposure modeling.

PMID- 15955254
TI  - A systematic review of how homeopathy is represented in conventional and CAM peer
      reviewed journals.
AB  - BACKGROUND: Growing popularity of complementary and alternative medicine (CAM) in
      the public sector is reflected in the scientific community by an increased number
      of research articles assessing its therapeutic effects. Some suggest that
      publication biases occur in mainstream medicine, and may also occur in CAM.
      Homeopathy is one of the most widespread and most controversial forms of CAM. The
      purpose of this study was to compare the representation of homeopathic clinical
      trials published in traditional science and CAM journals. METHODS: Literature
      searches were performed using Medline (PubMed), AMED and Embase computer
      databases. Search terms included "homeo-pathy, -path, and -pathic" and "clinical"
      and "trial". All articles published in English over the past 10 years were
      included. Our search yielded 251 articles overall, of which 46 systematically
      examined the efficacy of homeopathic treatment. We categorized the overall
      results of each paper as having either "positive" or "negative" outcomes
      depending upon the reported effects of homeopathy. We also examined and compared
      15 meta-analyses and review articles on homeopathy to ensure our collection of
      clinical trials was reasonably comprehensive. These articles were found by
      inserting the term "review" instead of "clinical" and "trial". RESULTS: Forty-six
      peer-reviewed articles published in a total of 23 different journals were
      compared (26 in CAM journals and 20 in conventional journals). Of those in
      conventional journals, 69% reported negative findings compared to only 30% in CAM
      journals. Very few articles were found to be presented in a "negative" tone, and
      most were presented using "neutral" or unbiased language. CONCLUSION: A
      considerable difference exists between the number of clinical trials showing
      positive results published in CAM journals compared with traditional journals. We
      found only 30% of those articles published in CAM journals presented negative
      findings, whereas over twice that amount were published in traditional journals.
      These results suggest a publication bias against homeopathy exists in mainstream
      journals. Conversely, the same type of publication bias does not appear to exist
      between review and meta-analysis articles published in the two types of journals.

PMID- 15955255
TI  - Perceptions of substance use, treatment options and training needs among Iranian
      primary care physicians.
AB  - In order to be optimally effective, continuing training programmes for health
      care professionals need to be tailored so that they target specific knowledge
      deficits, both in terms of topic content and appropriate intervention strategies.
      A first step in designing tailored treatment programmes is to identify the
      characteristics of the relevant health-care professional group, their current
      levels of content and treatment knowledge, the estimated prevalence of drug and
      alcohol problems among their patients and their preferred options for receiving
      continuing education and training. This study reports the results of a survey of
      53 primary care physicians working in Iran. The majority were male, had a mean
      age of 44 years and saw approximately 94 patients per week. In terms of their
      patients' drug use, primary care physicians thought most patients with a
      substance use problem were male, women were most likely to use tobacco (52%),
      opium (32%) and marijuana/hashish and young people were most likely to use
      tobacco, alcohol, marijuana and heroin. Counselling and nicotine patches were the
      treatments most commonly provided. Although the majority (55%) reported referring
      patients to other services, more than a third did not. Most primary care
      physicians reported being interested in attending further training on substance
      abuse issues. The implications of these data for ongoing education and training
      of primary care physicians in Iran are discussed.

PMID- 15955256
TI  - Pregnancy-induced obsessive compulsive disorder: a case report.
AB  - Pregnancy is a well-recognised risk factor in precipitating obsessive-compulsive
      disorder. We present and discuss a case with the onset of obsessive-compulsive
      disorder in the fourth month of gestation, which fully recovered two weeks after
      delivery. The phenomenology of the observed disorder was similar to earlier
      reports of obsessive-compulsive disorder in pregnancy, i.e. the obsessions and
      compulsions were predominantly related to the concern of contaminating the foetus
      resulting in washing compulsions. Despite the initial success with anti
      obsessional drugs, the patient stopped the medication in the last month of
      gestation. Nevertheless, she fully recovered two weeks after the delivery without
      any psychiatric intervention. There were no obsessive-compulsive symptoms at one
      year follow up. The possible mechanisms involved in the aetiology of this case,
      and future research directions in understanding the role of pregnancy in OCD are
      discussed.

PMID- 15955258
TI  - Internationally trained dentists in Canada: an alternative view.

PMID- 15955257
TI  - Does treating obesity stabilize chronic kidney disease?
AB  - BACKGROUND: Obesity is a growing health issue in the Western world. Obesity, as
      part of the metabolic syndrome adds to the morbidity and mortality. The incidence
      of diabetes and hypertension, two primary etiological factors for chronic renal
      failure, is significantly higher with obesity. We report a case with morbid
      obesity whose renal function was stabilized with aggressive management of his
      obesity. CASE REPORT: A 43-year old morbidly obese Caucasian male was referred
      for evaluation of his chronic renal failure. He had been hypertensive with well
      controlled blood pressure with a body mass index of 46 and a baseline serum
      creatinine of 4.3 mg/dl (estimated glomerular filtration rate of 16 ml/min). He
      had failed all conservative attempts at weight reduction and hence was referred
      for a gastric by-pass surgery. Following the bariatric surgery he had
      approximately 90 lbs. weight loss over 8-months and his serum creatinine
      stabilized to 4.0 mg/dl. CONCLUSION: Obesity appears to be an independent risk
      factor for renal failure. Targeting obesity is beneficial not only for better
      control of hypertension and diabetes, but also possibly helps stabilization of
      chronic kidney failure.

PMID- 15955259
TI  - Clinical management of 3 mandibular incisors with 2 separate canals and foramina:
      case report.
AB  - This case report describes the root canal treatment of 3 mandibular incisors,
      each with 2 separate canals and foramina, in 1 patient. The case demonstrates an
      unusual morphological configuration of the root canal system and supplements
      previous reports of the existence of such configurations in mandibular incisors.

PMID- 15955260
TI  - Supernumerary premolars associated with dens evaginatus: report of 2 cases.
AB  - Dens evaginatus is a dental anomaly found predominantly in people of Mongoloid
      origin. Dentists practising in Western countries should also be aware of this
      condition because of the increasing migration of people from Asia. Supernumerary
      premolars are uncommon but may be found incidentally during radiographic
      examination of teeth with dens evaginatus. This article reports 2 cases of
      concomitant occurrence of supernumerary premolars and dens evaginatus. The
      presence of a supernumerary premolar in 1 quadrant is an indication for
      radiographic examination of all other premolar regions.

PMID- 15955261
TI  - Residual neonatal teeth: a case report.
AB  - A case is presented in which an infant required extraction of 2 residual neonatal
      teeth. Some authors suggest routine curettage of the extraction sites of natal
      and neonatal teeth to prevent the development of residual teeth. In light of the
      rare occurrence of such residual teeth, this may represent overtreatment.
      Curettage at the time of extraction is recommended only in cases where the
      administration of an injectable local anesthetic is required because of greater
      gingival attachment.

PMID- 15955262
TI  - Tobacco use among young North American aboriginal athletes.
AB  - Tobacco use remains a major cause of preventable illness and death in North
      America. Although reported smoking rates have decreased, they remain high among
      the young and among Aboriginal people. As part of an oral health promotion
      project, a convenience sample of 163 Aboriginal athletes participating in the
      2002 North American Indigenous Games completed a self-administered questionnaire
      addressing tobacco use and knowledge of tobacco effects. Mean age of athletes was
      19.6 years (SD 7.4); most were male and Canadian citizens. Only 22 participants
      reported current smoking; past use of tobacco was more common, with 58 reporting
      a history of smoking. Although age was not associated with current smoking, older
      athletes were significantly more likely (p <or=0.05) to have smoked. Twenty-three
      athletes reported ever using smokeless tobacco, with 9 reporting current daily
      use. Athletes were knowledgeable about tobacco effects on oral health. This study
      shows substantially lower tobacco use among this group of young Aboriginal
      athletes than the North American average. These findings suggest that
      participation in organized sports may be a protective factor against tobacco use
      in a population known to have high smoking rates.

PMID- 15955263
TI  - Class I and Class II silver amalgam and resin composite posterior restorations:
      teaching approaches in Canadian faculties of dentistry.
AB  - A 10-question survey was mailed to the 10 Canadian faculties of dentistry to
      determine current approaches to teaching undergraduates about silver amalgam and
      resin composite for posterior restorations in adults and children. Responses were
      received from all 10 pedodontic programs and from 8 of the 10 operative and
      restorative programs. The use of silver amalgam and posterior composite for
      restorations of primary and permanent teeth is covered in the curricula of all
      dental schools, but the relative emphasis on the 2 materials varies. In the
      operative and restorative programs, curriculum time devoted to silver amalgam is
      either greater than or equal to that devoted to posterior composite. Five of the
      8 schools reported greater educational emphasis on silver amalgam for the
      permanent dentition; however, course directors noted that the preference among
      patients seen in clinics is tending toward composite restorations. Curricula
      appear designed to educate students about the optimal use of both materials.
      Requirements for performance of restorations during training generally do not
      specify the type of material; these requirements range from 60 restorations to
      250 surfaces. Five of the 8 schools conduct clinical competency tests with both
      materials. The responses from the pedodontic programs were more diverse. The
      proportion of curriculum time devoted to each type of material in these programs
      ranged from less than 25% to more than 75%. Five schools reported more emphasis
      on silver amalgam, 3 schools reported equal emphasis, and 2 schools reported more
      emphasis on posterior composite. No clinical requirements were specified in any
      of the undergraduate pedodontic programs. Within some of the faculties, there
      were differences between the operative and restorative program and the pedodontic
      program with respect to emphasis on different materials for the posterior
      dentition.

PMID- 15955264
TI  - Neonatal HSV infections: the global picture.

PMID- 15955265
TI  - Neonatal HSV infection Part I: continuing challenges.
AB  - Neonatal herpes still presents diagnostic and management problems in view of
      continuing high mortality and morbidity rates, even though effective antiviral
      therapy is now available. This article, which reviews current knowledge and
      progress, provides practical guidelines for the diagnosis, management and
      treatment of neonatal herpes, based on the literature and decades of experience.
      It is advisable to focus at the local level on detecting maternal cervical
      infection, applying the available diagnostic tools and obtaining appropriate
      medical specialty consultations, as well as improving health worker and patient
      education about detecting and managing herpes simplex virus infections.

PMID- 15955266
TI  - Epidemiological, clinical and laboratory aids for the diagnosis of neonatal
      herpes -- an Australian perspective.
AB  - Neonatal herpes is rare in Australia, possibly because of the older average age
      at pregnancy compared with other developed countries, low herpes simplex virus
      (HSV)-2 seroprevalence in the general community, low risk of HSV-2 acquisition
      during pregnancy and relatively high HSV-1 seroprevalence in adults. Guidelines
      on herpes management in pregnancy have been produced by the Australian Society
      for Infectious Diseases and endorsed by the Australian College of Obstetricians
      and Gynaecologists. However, diagnosing and managing neonatal infection remains
      difficult. Until an effective strategy to prevent neonatal herpes is developed,
      our efforts should focus on improving early diagnosis of HSV disease in the
      neonate and developing more effective strategies to reduce early reactivation and
      long-term morbidity.

PMID- 15955267
TI  - Neonatal HSV infection Part II: Obstetric considerations -- a tale of hospitals
      in two cities (Seattle and Atlanta, USA).
AB  - This article presents various aspects of maternal genital and neonatal herpes
      simplex virus (HSV)-1 and HSV-2 infection for hospitals in two cities in the USA 
      Seattle and Atlanta - to serve as models for the different subpopulations within
      developed and developing countries. Reasons are given for the disparity between
      the increasing rates of genital HSV-1 and HSV-2 infections observed in several
      areas of the world and the general low rates of newborn herpes noted in sites
      other than some hospitals in Seattle, Atlanta, Cincinnati and Helsinki. A key
      reason for the disparity appears to be the continuing difficulty in diagnosing
      maternal genital herpes and neonatal herpes. Contributing factors include the
      variability in different communities in sexual behaviour patterns, and in the
      rates of maternal genital HSV infection, caesarean sections and postmortem
      procedures. Unresolved challenges in the obstetric management of genital herpes
      aimed at preventing neonatal herpes are also presented.

PMID- 15955268
TI  - Management of genital herpes during pregnancy: the French experience.
AB  - The prevalence and incidence of genital herpes are increasing worldwide.
      Conversely, the incidence of neonatal herpes shows global discrepancies: very
      higher numbers of cases are reported in parts of the USA, whereas rates remain
      low across much of Europe. As illustrated by the French experiences reported
      here, regionally appropriate management strategies for genital herpes during
      pregnancy do not alone account for differences in neonatal herpes rates.

PMID- 15955269
TI  - Expert commentary: genital herpes transmission.

PMID- 15955270
TI  - HHV-8 infection in African children.
AB  - Human herpesvirus 8 (HHV-8) is prevalent in Africa and parts of southern Europe,
      but less common elsewhere. It is analogous to its distant relative, the Epstein
      Barr virus, in that it rarely causes disease in the immunocompetent host but is
      highly oncogenic when associated with immunosuppression or HIV-1 infection. HHV-8
      infection is endemic in sub-Saharan Africa, where high seroprevalence rates of up
      to 58% in young children were found in Ghana, Tanzania, Cameroon, Uganda and
      Egypt. Paediatric HHV-8 transmission has been studied in various African
      populations. Frequent detection of the virus from oral secretions suggests the
      horizontal route is the most common way to acquire the virus during childhood. A
      clinical presentation characterized by a self-limited maculopapular rash and
      fever was associated with HHV-8 primary infection in Egyptian children.

PMID- 15955271
TI  - Intravenous immunoglobulins in MS: a panacea lacking approval?

PMID- 15955272
TI  - Education and MS.

PMID- 15955273
TI  - Intravenous Immunoglobulins in MS.
AB  - High-dose intravenous immunoglobulins (IVIg) have become a successful new
      treatment regimen in neurological autoimmune diseases. Most autoimmune disorders
      are heterogeneous, implicating cellular and humoral immune mechanisms, and this
      pathogenesis also applies to MS. Many in vivo and in vitro experimental studies
      have shown that IVIg can therapeutically interfere with the immune system at
      several levels, but only some are likely to be relevant in MS. Clinical trials of
      IVIg have investigated the effect on different disease courses and stages of MS.
      Data show that IVIg have beneficial effects in relapsing-remitting disease, but
      probably no effect during the secondary progressive phase. IVIg are, therefore,
      currently considered in some countries as secondline treatments for patients with
      relapsing-remitting disease when first-line drugs are not tolerated. Despite
      promising data from animal experiments that IVIg may induce remyelination, human
      treatment trials have not demonstrated a clinically relevant improvement.

PMID- 15955274
TI  - Pathological differences in acute inflammatory demyelinating diseases of the
      central nervous system.
AB  - This article reviews the different pathological and immunological features of MS,
      acute variants of MS and acute disseminated encephalomyelitis (ADEM). T-cell
      mediated inflammatory reactions are involved in all acute inflammatory diseases
      of the central nervous system, but the diseases discussed also exhibit distinct
      immunopathological features. The perivascular infiltrate of T-cells and
      macrophages seen in ADEM resembles the pathological pattern found in experimental
      autoimmune encephalomyelitis. In addition, there is evidence that humoral
      mechanisms play a crucial role in some acute MS lesions, Devics syndrome and
      Marburgs syndrome. Analysis of acute MS lesions shows many different structural
      and immunological features, indicating that different mechanisms may be involved
      in lesion formation. Distinct subtypes of acute lesions exhibit either
      similarities with T-cell-mediated autoimmune encephalomyelitis or signs of
      primary oligodendrocyte damage.

PMID- 15955275
TI  - Medical education and MS: getting the training right.
AB  - Medical education needs continuous improvements to meet the changing demands of
      medical practice in the 21st century. We need to review the teaching methods used
      and the curriculum taught during various stages of a doctors training. General
      practitioners need to recognize the symptoms indicative of MS and refer the
      patient to a specialist; neurologists should confirm the diagnosis, and
      effectively treat, manage and support the patient. Training should be adapted to
      reflect these different tasks and equip the physician accordingly. We suggest a
      training programme for undergraduate students comprising three lectures and two
      interactive sessions. These would provide the student with a basic knowledge of
      MS and its management. For those wishing to specialize in neurology, we recommend
      a series of eight lectures, interactive sessions discussing case reports with
      typical and atypical presentations, two magnetic resonance imaging reading
      sessions with a specialist neuroradiologist and active practice in an MS clinic.

PMID- 15955276
TI  - MS Management in Complex Cases: report from the MS Forum satellite symposium at
      the 20th ECTRIMS Congress, 6 October 2004, Vienna, Austria.
AB  - The disease course of MS is varied and unpredictable. Patients, therefore, need
      'expert' advice, which puts a great burden on the physician, especially when
      results from large-scale studies are unavailable. Educational forums, such as MS
      Forum symposia, are ideal opportunities to discuss diagnosing, treating and
      managing complex MS.

PMID- 15955277
TI  - Interferons in MS Treatment: report from the Canadian MS Forum symposium, 26-29
      August 2004, Quebec, Canada.
AB  - The epidemiology of MS in Newfoundland and Labrador was one of the topics
      discussed at the first Canadian MS Forum symposium, held in St John's,
      Newfoundland, Canada. Also discussed were the benefits of neuroprotection and
      neuroregeneration in MS, and diagnosis using the McDonald criteria. The efficacy
      of interferon beta-1b treatment and evidence on new disease hypotheses were
      reviewed. Latest news on the growing success and reach of the MS Forum was also
      presented, with the aim of providing a link between MS experts and institutions.

PMID- 15955278
TI  - MS Across Continents: Challenging our Knowledge of MS in Asia and the Middle
      East. Report from the 2nd MS Forum Pan-Asian Conference, 19-20 November 2004, Ho
      Chi Minh City, Vietnam.
AB  - Multiple sclerosis in Asia and the Middle East shares many similarities with the
      disease seen in Caucasian populations, but there are notable and important
      differences. These need to be characterized and defined to enable correct
      diagnosis. Classifying and diagnosing MS in Asian and Middle Eastern populations
      were themes of the 2nd MS Forum Pan-Asian conference. Participants also discussed
      other 'hot topics', such as health economics and research outcome, diagnostic red
      flags and pitfalls with diagnostic imaging, early magnetic resonance imaging
      changes, pathology and axonal loss, neuroprotection and childhood MS.

PMID- 15955279
TI  - Genetic immunisation of cattle against bovine herpesvirus 1: glycoprotein gD
      confers higher protection than glycoprotein gC or tegument protein VP8.
AB  - Bovine herpesvirus 1 (BoHV-1) has frequently been used as a model for testing
      parameters affecting DNA immunisation in large animals like cattle. However, the
      selection of target antigens has been poorly studied, and most of the experiments
      have been conducted in mice. In the present study, we demonstrated in cattle that
      a DNA vaccine encoding BoHV-1 glycoprotein gD induces higher neutralising
      antibody titres than vaccines encoding BoHV-1 gC. Additionally, we show that a
      DNA vaccine encoding a secreted form of gD induces a higher immune response than
      a vaccine encoding full-length gD. However, the enhanced immunogenicity
      associated with the secretion of gD could not be extended to the glycoprotein gC.
      The current study also describes for the first time the development and the
      evaluation of a DNA vaccine encoding the major tegument protein VP8. This
      construct, which is the first BoHV-1 plasmid vaccine candidate that is not
      directed against a surface glycoprotein, induced a high BoHV-1 specific cellular
      immunity but no humoral immune response. The calves vaccinated with the
      constructs encoding full-length and truncated gD showed a non-significant tenfold
      reduction of virus excretion after challenge. Those calves also excreted virus
      for significantly (p < 0.05) shorter periods (1.5 days) than the non-vaccinated
      controls. The other constructs encoding gC and VP8 antigens induced no
      virological protection as compared to controls. Altogether the DNA vaccines
      induced weaker immunity and protection than conventional marker vaccines tested
      previously, confirming the difficulty to develop efficient DNA vaccines in large
      species.

PMID- 15955280
TI  - Discrepancies between the isolation of Salmonella from mesenteric lymph nodes and
      the results of serological screening in slaughter pigs.
AB  - Most Salmonella control programmes are based on serological testing in the
      slaughterhouse. However, from a point of view of carcass contamination, it is
      rather the presence of Salmonella spp. in the animal at the time of slaughter
      that is important. The aim of this cross-sectional study was to investigate the
      possible discrepancies between the isolation of Salmonella spp. in the mesenteric
      lymph nodes and the results of serological screening. In total, 1821 fattening
      pigs originating from 60 Belgian farrow-to-finish herds were sampled in the
      slaughterhouse. The serum samples were analysed using an indirect mix-ELISA for
      the presence of Salmonella antibodies and evaluated at 3 cut-off values namely
      10, 20, and 40% Optical Density (OD). All mesenteric lymph node samples were
      submitted to qualitative Salmonella isolation and a representative number of
      isolates was serotyped. From each herd, 30 animals were screened both
      serologically and bacteriologically and the herd was considered as positive when
      at least one sample was positive. At the herd level, 83.6% (cut-off OD 40%) to
      100.0% (cut-off OD 10%) of the herds from which Salmonella had been isolated were
      evaluated as seropositive. At the individual level, only 34.5% (cut-off OD 40%)
      to 82.8% (cut-off OD 10%) of the animals from which Salmonella had been isolated
      were seropositive. Overall, a weak agreement was found between bacteriology and
      serology for Salmonella diagnosis. If pig herds are categorised using serological
      tests in the slaughterhouse, one should be aware of the fact that slaughter pigs
      can still harbour Salmonella spp. in the mesenteric lymph nodes, without being
      detected in serological tests. The cut-off value used to evaluate a sample as
      serologically positive and the number of samples per herd are of major importance
      to classify herds correctly in order to protect human health.

PMID- 15955281
TI  - Depletion of pulmonary intravascular macrophages partially inhibits
      lipopolysaccharide-induced lung inflammation in horses.
AB  - Horses are unique in their extreme sensitivity to endotoxin-induced cardio
      pulmonary shock and mortality. The mechanisms behind increased sensitivity of the
      horse to endotoxin remain unknown. Pulmonary intravascular macrophages (PIMs) are
      pro-inflammatory cells occurring in horses. Because the functions of equine PIMs
      in endotoxemia remain unknown, we studied the role played by equine PIMs in
      endotoxin-induced pulmonary pathophysiology. We achieved this by using a recently
      developed protocol to deplete PIMs in order to compare lipopolysaccharide (LPS)
      induced pulmonary responses in horses with or without PIMs. Horses treated with
      gadolinium chloride (GC; 10 mg/kg intravenous) to deplete PIMs or endotoxin-free
      saline (n = 4) were injected with Escherichia coli LPS (E. coli LPS; 50 ng/kg
      intravenously) 48 h after GC or saline. Control horses (n = 5) received two
      injections of endotoxin-free saline at 48 h intervals. All the horses were
      euthanized 2 h after LPS or saline challenge. Immunohistology for the PIMs showed
      their reduced numbers in GC-treated horses. The LPS treatment of normal and GC
      treated horses increased diastolic and systolic pulmonary arterial pressures at
      30 min compared to the saline-treated horses (P < 0.05). However, horses pre
      treated with GC did not have an LPS-induced increase in mean pulmonary arterial
      pressure compared to the LPS-treated horses (P < 0.05). Light and electron
      microscopic immunocytochemistry detected extensive labeling for LPS in PIMs of
      LPS-treated horses. Both the LPS-treated groups had more alveolar septal cells
      positive for TNF-alpha and IL-1beta compared to control horses, which did not
      receive LPS (P < 0.05). However, GC-treated horses challenged with the LPS showed
      less IL-1beta-positive cells (P < 0.05). Immuno-electron microscopy localized TNF
      alpha and IL-1beta in PIMs. These new data show that PIMs endocytose LPS and
      contain TNF-alpha and IL-1beta and their depletion partially inhibits LPS-induced
      pulmonary inflammatory responses.

PMID- 15955282
TI  - Immunomodulatory effect of plasmids co-expressing cytokines in classical swine
      fever virus subunit gp55/E2-DNA vaccination.
AB  - The aim of this study was to determine the immunomodulatory effects of IL-12, IL
      18 and CD154 (CD40 ligand, CD40L) in DNA-vaccination against the classical swine
      fever virus. Four recombinant plasmids were constructed including the CSFV coding
      region for the glycoprotein gp55/E2 alone or together with porcine IL-12, IL-18
      or CD154 genes. Five groups of four pigs each were immunized intramuscularly
      (i.m.) three times with the respective constructs. The control group was
      inoculated with empty plasmid DNA. Eighteen days after the final immunization,
      the pigs were challenged with a lethal dose of CSFV strain Eystrup and monitored
      for a further 16 days. This study showed that co-delivery of IL-18 and CD154
      induced an earlier appearance of serum antibodies, reduced B-cell deficiency
      after infection and protected pigs against a lethal CSFV infection. In contrast,
      co-delivery of IL-12 led to a reduced titer of neutralizing antibodies and
      protection against a lethal CSFV challenge in comparison to the other pigs and to
      pigs that were immunized with a gp55/E2 plasmid alone.

PMID- 15955283
TI  - Avirulence of viable but non-culturable Listeria monocytogenes cells demonstrated
      by in vitro and in vivo models.
AB  - The virulence of Viable But Non-Culturable (VBNC) cells of 4 strains of Listeria
      monocytogenes was investigated in both a human adenocarcinoma cell line (HT-29)
      and a mouse model. LO 28, ATCC 19115 and CNL 895807 strains of Listeria
      monocytogenes became VBNC when incubated in microcosm water at 20 degrees C and
      Scott A strain at 4 degrees C. No culturable bacteria were detected in the VBNC
      state, although 104 active cells/mL were found by the Direct Viable Count (DVC)
      and CTC-DAPI double staining methods. A comparison of virulence in both human
      adenocarcinoma cell line HT-29 and the mouse model showed that culturable
      controls were more virulent than VBNC cells, which appeared to be avirulent
      regardless of the virulence methods applied. Pathogenicity was tested in each
      model and was lost concomitantly with culturability, whereas some cells were
      still metabolically active (determined by CTC and DVC). Moreover, amplification
      of a 388 bp fragment with Immunocapture-PCR revealed the presence of Listeria
      monocytogenes DNA in all mixed spleen samples after intravenous injection of VBNC
      cells. These results demonstrate that VBNC cells were present in the mouse
      spleens. The results of the study suggest that Listeria monocytogenes strains
      might remain in the aquatic environment for prolonged periods in the VBNC state
      but these cells were not pathogenic in the conditions tested. These findings
      demonstrate the value of VBNC studies and show the need to investigate the role
      of VBNC cells in environmental transmission of Listeria monocytogenes. Further
      studies are needed in order to investigate the virulence of VBNC cells of
      Listeria monocytogenes after recovery of a culturable state.

PMID- 15955284
TI  - Epizootic Rabbit Enteropathy: experimental transmission and clinical
      characterization.
AB  - In late 1996 in France, a severe digestive disease appeared in fattening domestic
      rabbits. Named the Epizootic Rabbit Enteropathy (ERE), this digestive syndrome
      has become the main cause of mortality in rabbit farming. The diagnosis in field
      conditions is difficult because co-infection with other common rabbit pathogens
      is frequent. By using specific pathogenic free (SPF) rabbits and starting from a
      field sample of intestinal contents of diseased animals, a virulent material
      (inoculum) was obtained free of almost all known pathogens but reproduced the
      symptoms and lesions of ERE. Four hundred and seven SPF rabbits were used in five
      trials to describe the disease. ERE is characterized by a high contagiousness, 30
      to 40% mortality in a few days and about 100% morbidity whatever the dose of the
      inoculum used. Clinical signs and lesions evolved acutely with the first sign
      (rambling noise) appearing one day after inoculation and the disease peaking 4 to
      6 days later. Growth was strongly lowered from the second day to the end of the
      second week. Rambling noise and distended abdomen were frequent, mucus excretion
      and cecal impaction were frequent but not constant. ERE at necropsy was
      characterized by the absence of any inflammatory or congestive lesions on the gut
      or on other organs but with the typical presence of a stomach and/or duodenum
      dilated by liquid and gas and by the absence of specific histological lesions.
      The etiological agent has not been identified yet, but we demonstrate that the
      intestinal content was infectious as early as the second day. This work
      constitutes the experimental basis for studies on this emerging disease within
      the framework of etiological research led in different European laboratories
      working with the infectious material.

PMID- 15955285
TI  - Poultry, pig and the risk of BSE following the feed ban in France--a spatial
      analysis.
AB  - A spatial analysis was carried out in order to analyse the reason why the risk of
      Bovine Spongiform Encephalopathy (BSE) was spatially heterogeneous in France,
      during the period following the feed ban of Meat and Bone Meal to cattle. The
      hypothesis of cross-contamination between cattle feedstuff and monogastric
      feedstuff, which was strongly suggested from previous investigations, was
      assessed, with the assumption that the higher the pig or poultry density is in a
      given area, the higher the risk of cross-contamination and cattle infection might
      be. The data concerned the 467 BSE cases born in France after the ban of meat and
      bone meal (July 1990) and detected between July 1st, 2001 and December 31, 2003,
      when the surveillance system was optimal and not spatially biased. The disease
      mapping models were elaborated with the Bayesian graphical modelling methods and
      based on a Poisson distribution with spatial smoothing (hierarchical approach)
      and covariates. The parameters were estimated by a Markov Chain Monte Carlo
      simulation method. The main result was that the poultry density did not
      significantly influence the risk of BSE whereas the pig density was significantly
      associated with an increase in the risk of 2.4% per 10 000 pigs. The areas with a
      significant pig effect were located in regions with a high pig density as well as
      a high ratio of pigs to cattle. Despite the absence of a global effect of poultry
      density on the BSE risk, some areas had a significant poultry effect and the risk
      was better explained in some others when considering both pig and poultry
      densities. These findings were in agreement with the hypothesis of cross
      contamination, which could take place at the feedstuff factory, during the
      shipment of food or on the farm. Further studies are needed to more precisely
      explore how the cross-contamination happened.

PMID- 15955286
TI  - Neutrophil apoptosis during experimentally induced Staphylococcus aureus
      mastitis.
AB  - The objective of this study was to determine whether neutrophil apoptosis and
      their consequent elimination by macrophages from the mammary gland is modulated
      by an infection caused by Staphylococcus aureus (S. aureus). The study was
      performed on twenty mammary glands of 5 virgin heifers. A buffered physiological
      solution (PBS) was administered as a means of control into the mammary glands of
      the heifers and after 168 h, the glands were inoculated with S. aureus. The
      samples of cell populations were obtained by lavages of the mammary glands in 4
      intervals (24, 48, 72 and 168 h) after the experimental infection. Flow cytometry
      was used for determination of Annexin-V positivity and propidium iodide (PI)
      negativity of neutrophils. Light microscopy was used for determination of
      neutrophil karyopyknosis. Cytochemistry was used for the detection of
      myeloperoxidase-positive (MPO+) macrophages. Instillation of S. aureus resulted
      in an intramammary infection which persisted during the following experimental
      period. The total number of both Annexin-V-positive and PI negative neutrophils
      and karyopyknotic neutrophils peaked at 24 h after both of PBS and S. aureus
      administration. The highest percentages of Annexin-V-positive and PI negative
      neutrophils and karyopyknotic neutrophils were detected 48 and 168 h after PBS
      and S. aureus administration, respectively. The total number of MPO+ macrophages
      was the highest 24 h and 48 h after PBS and S. aureus administration,
      respectively; the percentage of MPO+ macrophages was the highest at 72 h in both
      cases. The dynamics of resolution of mastitis caused by S. aureus was very
      similar to the resolution of inflammatory response of the mammary gland after PBS
      administration. Mechanisms of cell pathogen elimination as well as inflammation
      resolution were very intensively involved; nevertheless, the mammary gland
      infection persisted. An early inclusion of the mechanisms of an acute
      inflammatory resolution thus paradoxically led to chronic infection.

PMID- 15955287
TI  - Salmonella in sows: a longitudinal study in farrow-to-finish pig herds.
AB  - Besides finishing pigs, sows are also believed to be important in the
      epidemiology of Salmonella. The study objective was to investigate the prevalence
      of Salmonella excretion in sows during an entire reproductive cycle. In 3 farrow
      to-finish herds, groups of 34, 40 and 32 sows, respectively, were sampled
      serially. Faecal samples, environmental swabs and feed samples were taken and
      submitted to a qualitative Salmonella isolation. All isolates were characterised
      using RAPD and a representative number of isolates was serotyped. The prevalence
      of Salmonella excretion was < 10% during gestation, around farrowing and during
      lactation, but a significant increase in the number of Salmonella excreting sows
      was found in herds A (p < 0.01) and C (p = 0.02) after weaning. S. Infantis was
      the most prevalent serotype in herd A, S. Derby in herds B and C. Except for the
      S. Infantis group in herd A, all isolates within each group of the RAPD analysis
      belonged to the same serotype. Three sows in herd A and 1 sow in herd C shed
      different serotypes at different time points. The present results indicate that
      sows can maintain Salmonella infections in farrow-to-finish herds and that culled
      sows, leaving the herd after weaning, may constitute a substantial risk for
      contamination of their carcasses with Salmonella.

PMID- 15955288
TI  - The negative acute phase response of serum transthyretin following Streptococcus
      suis infection in the pig.
AB  - Transthyretin (TTR) is a serum protein which is a negative acute phase reactant
      in humans and levels of TTR are routinely measured as an indicator of health
      status. Such tests have yet to be established for the pig. In order to measure
      serum TTR in the pig during an acute phase response an assay was developed using
      anti-human TTR antibodies which cross reacted with porcine TTR. The assay had a
      detection limit of 32 microg/mL while the mean concentration of transthyretin
      measured in healthy pig serum was 302 +/- 8 microg/mL (n = 63). There was no
      significant difference in the serum concentration of TTR in three different age
      groups from 10 to 25 weeks. Following Streptococcus suis type 2 infection
      transthyretin showed a negative acute phase response with serum concentrations
      reaching a significantly lower level at two days following infection.

PMID- 15955290
TI  - Potential increased risk of hypersensitivity pneumonitis (HP) in complementary
      medicine practitioners associated with handling exotic mushroom varieties.

PMID- 15955291
TI  - Petit bourgeois health care? The big small-business of private complementary
      medical practice.
AB  - Although small business private complementary medicine (CAM) has grown to be a
      significant provider of health care in many Western societies, there has been
      relatively little research on the sector in business terms and on its wider socio
      economic position and role. Using a combined questionnaire and interview survey,
      and the concept of small business petit bourgeoisie as a framework, this paper
      considers the character of therapists and their businesses in England and Wales.
      The findings suggest that typical of the core characteristics of both the petit
      bourgeoisie and therapists are the selling of goods with a considerable market
      viability, at the same time financial insecurity; the modest size of businesses;
      small amounts of direct employment generation and business owners undertaking
      everyday 'hands-on' work themselves. Certain of the therapists' and business
      characteristics depart from the stereotypical image of a small businesses class,
      such as the high incidence of part-time self-employment and incomes being
      supplemented often by unrelated waged employment. However, given the acknowledged
      diversity of the petit bourgeoisie between societies and over time, the framework
      is arguably appropriate in this context, and private CAM a latest guise. Indeed,
      just as the petit bourgeoisie have traditionally found market niches either
      neglected or rejected by bigger business, small business CAM has provided the
      forms of health care neglected and sometimes rejected by orthodox medicine.

PMID- 15955292
TI  - Complementary and alternative medicine use in patients with haematological
      malignancies in Europe.
AB  - This study reports upon a descriptive cross-sectional survey assessing the use of
      complementary and alternative medicine (CAM) in patients with haematological
      cancers. Twelve European countries contributed data from patients with
      haematological cancers, as part of a larger study. Sixty-eight patients with
      haematological cancer participated. Among the participants, 26.5% used some form
      of CAM after the cancer diagnosis. The most common therapies used were homeopathy
      (38.9%), herbal medicine (22.2%) various psychic therapies, such as use of
      mediums, healers, rebirthing or past life regression therapy (22.2%). A
      particular profile of a CAM user was not evident in the sample. Moderate levels
      of satisfaction with CAM were reported. Patients commonly used CAM to increase
      the ability of their body to fight cancer and to improve physical and emotional
      well-being. Information about CAM was received mainly from friends or family. As
      CAM use in patients with haematological malignancies is common, clinicians should
      assist patients who want to use CAM to make an appropriate decision, and improve
      communication with them about CAM use in an open and non-judgemental dialogue.

PMID- 15955293
TI  - Informing nurses of the lived experience of acupuncture treatment: a
      phenomenological account.
AB  - Acupuncture is a component of Traditional Chinese Medicine, focusing on a
      holistic, energy-based approach to the individual, rather than a disease
      oriented, diagnostic, and treatment model. Nurses are increasingly involving
      themselves in the use of acupuncture as practitioners and as supporters of
      acupuncture in mainstream health care. This project described the lived
      experience of acupuncture treatment, with specific objectives to: inform nurses
      of people's experiences of having acupuncture; give nurses the language to
      explain to patients the experience of having acupuncture; and create
      possibilities for offering acupuncture as an informed choice of treatment in
      nursing and health care. The phenomenon of experiencing acupuncture was located
      within the participants' accounts of what it was like for them before, during,
      and after treatment.

PMID- 15955294
TI  - Acupuncture use for pre-birth treatment. A literature review and audit-based
      research.
AB  - Traditionally acupuncture at four points, Yanglingquan GB-34, Zusanli ST-36,
      Sanyinjiao SP-6 and Zhiyin BL-67, has been used for pre-birth treatments
      (Maciocia and West (eds.), Acupuncture in Pregnancy and Childbirth, Churchill
      Livingston, New York, 2000, pp. 559-575, Chapter 44). These points are
      specifically used to prepare the woman's body for birth, with an emphasis on
      preparing the cervix and pelvis for labour. Midwives in one District Health Board
      region in New Zealand who have had basic training in acupuncture techniques have
      been providing treatments for their clients prior to the estimated delivery date
      (EDD). A retrospective audit of the midwives practicing this technique was
      conducted to cover a 12-month period and a decrease in medical inductions and
      caesarean sections compared to the overall maternity report figures was apparent.
      The research was further informed by a literature review. This paper discusses
      both the audit and the literature review.

PMID- 15955295
TI  - Awareness and practice of complementary therapies in hospital and community
      settings within Essex in the United Kingdom.
AB  - Enhanced public interest calls for integration of Complementary treatments within
      allopathic medicine. The Foundation of Integrated Medicine issued guidelines for
      the use of complementary therapies in June 2003. The National Institute of
      Clinical Excellence (NICE) backed the use of Alternative Therapies in a paper in
      November 2003. The nursing and midwifery council (NMC) issued a position
      statement (December 2000) advocating all nurses and midwives using complementary
      or alternative therapies must ensure that they are individually competent to
      practice. For the service user, the NMC stipulated that these therapies needed to
      be safe and used as part of the therapeutic process. This included the recipient
      consenting to treatment. This has enabled nurses to expand their practice to
      integrate Complementary treatments into nursing care within the National Health
      Service. High-quality care is focused on client's individualized needs, based on
      current government initiatives (Making a Difference, 2000; Government response to
      the House of Lords select committee's report on complementary and alternative
      medicine, CM5124, The Stationary Office, London) (NHS Choice Agenda 2004).
      Following the Patient's charter (DoH, 1991) and the more recent NHS Plan (2001),
      service users are no longer intimidated by the authority-based structure and
      speak out against various decisions and the right to take part in decision
      making. This study investigated the awareness of complementary therapies by
      healthcare professionals currently employed by a local healthcare Trust. Data
      were also gathered on qualifications in complementary therapy and hospital and
      community sites of practice. We found a mismatch between the referrals staff
      recommended to clients and the treatment available within the practice areas. On
      the basis of our findings, we developed a new policy [Richardson J, Brennan AM.
      Complementary therapies in the N.H.S. service development in a local district
      general hospital. Complement Ther Nursing Midwifery 1995;1:89-92] for the
      provision of complementary therapies within the local health service.

PMID- 15955296
TI  - ATC policy on the conservation of plants used in aromatherapy.

PMID- 15955298
TI  - Functional consequences of heterogeneous gap junction channel formation and its
      influence in health and disease.
AB  - The capacity of multiple connexins to hetero-oligomerize into functional
      heterogeneous gap junction channels has been demonstrated in vivo, in vitro, and
      in nonmammalian expression systems. These heterogeneous channels display gating
      activity, channel conductances, selectivity and regulatory behaviors that are
      sometimes not predicted by the behaviors of the corresponding homogeneous
      channels. Such observations suggest that heteromerization of gap junction
      proteins offers an efficient cellular strategy for finely regulating cell-to-cell
      communication. The available evidence strongly indicates that heterogeneous gap
      junction assembly is important to normal growth and differentiation, and may
      influence the appearance of several disease states. Definitive evidence that
      heterogeneous gap junction channels differentially regulate electrical conduction
      in excitable cells is absent. This review examines the prevalence, regulation,
      and implications of gap junction channel hetero-oligomerization.

PMID- 15955299
TI  - Connexins and their environment: effects of lipids composition on ion channels.
AB  - Intercellular communication is mediated through paired connexons that form an
      aqueous pore between two adjacent cells. These membrane proteins reside in the
      plasma membrane of their respective cells and their activity is modulated by the
      composition of the lipid bilayer. The effects of the bilayer on connexon
      structure and function may be direct or indirect, and may arise from specific
      binding events or the physicochemical properties of the bilayer. While the
      effects of the bilayer and its constituent lipids on gap junction activity have
      been described in the literature, the underlying mechanisms of the interaction of
      connexin with its lipidic microenvironment are not as well characterized. Given
      that the information regarding connexons is limited, in this review, the specific
      roles of lipids and the properties of the bilayer on membrane protein structure
      and function are described for other ion channels as well as for connexons.

PMID- 15955300
TI  - Connexin phosphorylation as a regulatory event linked to gap junction channel
      assembly.
AB  - Gap junctions, composed of proteins from the connexin family, allow for
      intercellular communication between cells and are important in development and
      maintenance of cell homeostasis. Phosphorylation has been implicated in the
      regulation of gap junctional communication at several stages of the cell cycle
      and the connexin "lifecycle", such as trafficking, assembly/disassembly,
      degradation, as well as in the gating of "hemi" channels or intact gap junction
      channels. This review focuses on how phosphorylation can regulate the early
      stages of the connexin life cycle through assembly of functional gap junctional
      channels. The availability of sequences from the human genome databases has
      indicated that the number of connexins in the gene family is approximately 20,
      but we know mostly about how connexin43 (Cx43) is regulated. Recent technologies
      and investigations of interacting proteins have shown that activation of several
      kinases including protein kinase A, protein kinase C (PKC), p34(cdc2)/cyclin B
      kinase, casein kinase 1 (CK1), mitogen-activated protein kinase (MAPK) and
      pp60(src) kinase can lead to phosphorylation of the majority of the 21 serine and
      two of the tyrosine residues in the C-terminal region of Cx43. While many studies
      have correlated changes in kinase activity with changes in gap junctional
      communication, further research is needed to directly link specific
      phosphorylation events with changes in connexin oligomerization and gap junction
      assembly.

PMID- 15955301
TI  - Connexin phosphorylation as a regulatory event linked to channel gating.
AB  - The main proteins required for functional gap junction channels are known as
      connexins and most of their isoforms indicate that they can become
      phosphorylated. Connexin phosphorylation has been reported to participate in
      modifying junctional communication and the mechanisms involved apparently depend
      on which kinase becomes involved. Although multiple reports have suggested a
      strong influence of phosphorylation on channel gating, not enough physiological
      studies have been performed to determine precisely the gating mechanisms
      implicated. Moreover, gap junction channels follow other various gating
      mechanisms, including voltage gating and chemical gating, where phosphorylation
      could act as a modulator. The quest for this chapter has been to discriminate
      those instances where phosphorylation acts directly as a gating trigger and where
      it acts indirectly or only as a modulator. Despite recent efforts, the mechanisms
      involved in all these cases are barely understood.

PMID- 15955302
TI  - Connexin phosphorylation as a regulatory event linked to gap junction
      internalization and degradation.
AB  - Gap junction proteins, connexins, are dynamic polytopic membrane proteins that
      exhibit unprecedented short half-lives of only a few hours. Consequently, it is
      well accepted that in addition to channel gating, gap junctional intercellular
      communication is regulated by connexin biosynthesis, transport and assembly as
      well as the formation and removal of gap junctions from the cell surface. At
      least nine members of the 20-member connexin family are known to be
      phosphorylated en route or during their assembly into gap junctions. For some
      connexins, notably Cx43, evidence exists that phosphorylation may trigger its
      internalization and degradation. In recent years it has become apparent that the
      mechanisms underlying the regulation of connexin turnover are quite complex with
      the identification of many connexin binding molecules, a multiplicity of protein
      kinases that phosphorylate connexins and the involvement of both lysosomal and
      proteasomal pathways in degrading connexins. This paper will review the evidence
      that connexin phosphorylation regulates, stimulates or triggers gap junction
      disassembly, internalization and degradation.

PMID- 15955303
TI  - Sensitivity of the brain transcriptome to connexin ablation.
AB  - Extensive studies on mice with total or partial disruption of either connexin43
      (Cx43) or connexin32 (Cx32) have detected only subtle changes in central nervous
      system structure, growth, development, or function. We have used high density
      cDNA arrays to analyze the regulation, control, and coordination of the
      abundances of 7446 distinct transcripts in four brains, each of Cx43 null (K43),
      Cx43 heterozygous (H43), and Cx32 null (K32) mice as compared to the brains of
      wildtype (W) mice. The use of multiple samples allowed the determination of the
      statistical significance of gene regulation. Significantly regulated genes
      encoded proteins of all functional categories, extending beyond those that might
      be expected to depend on junctional communication. Moreover, we found a high
      degree of similarity between genes regulated in the K43 and H43 brains and a
      remarkable overlap between gene regulation in brains of K43 and K32. The
      regulated genes in both K43 and H43 brains showed an outstanding inverse
      coordination with the levels of expression of Cx43 in W brain, indicating that
      the regulated genes are largely predictable from their co-variance with Cx43 in
      the wildtype samples. These findings lead to the hypothesis that connexin
      expression may represent a central node in the regulation of gene expression
      patterns in brain.

PMID- 15955304
TI  - Gap junctional communication in tissue inflammation and repair.
AB  - Local injury induces a complex orchestrated response to stimulate healing of
      injured tissues, cellular regeneration and phagocytosis. Practically,
      inflammation is defined as a defense process whereby fluid and white blood cells
      accumulate at a site of injury. The balance of cytokines, chemokines, and growth
      factors is likely to play a key role in regulating important cell functions such
      as migration, proliferation, and matrix synthesis during the process of
      inflammation. Hence, the initiation, maintenance, and resolution of innate
      responses depend upon cellular communication. A process similar to tissue repair
      and subsequent scarring is found in a variety of fibrotic diseases. This may
      occur in a single organ such as liver, kidneys, pancreas, lung, skin, and heart,
      but fibrosis may also have a more generalized distribution such as in
      atherosclerosis. The purpose of this review is to summarize recent advances on
      the contribution of gap junction-mediated intercellular communication in the
      modulation of the inflammatory response and tissue repair.

PMID- 15955305
TI  - Gap junction- and hemichannel-independent actions of connexins.
AB  - Connexins have been known to be the protein building blocks of gap junctions and
      mediate cell-cell communication. In contrast to the conventional dogma, recent
      evidence suggests that in addition to forming gap junction channels, connexins
      possess gap junction-independent functions. One important gap junction
      independent function for connexins is to serve as the major functional component
      for hemichannels, the un-apposed halves of gap junctions. Hemichannels, as
      independent functional units, play roles that are different from that of gap
      junctions in the cell. The other functions of connexins appear to be gap junction
      and hemichannel-independent. Published studies implicate the latter functions of
      connexins in cell growth, differentiation, tumorigenicity, injury, and apoptosis,
      although the mechanistic aspects of these actions remain largely unknown. In this
      review, gap junction- and hemichannel-independent functions of connexins are
      summarized, and the molecular mechanisms underlying these connexin functions are
      speculated and discussed.

PMID- 15955307
TI  - Report on the 2nd EMBO Workshop on "Pathogenesis of Amoebiasis: From Genomics to
      Disease" held at Ein Gedi, Israel, November 16-20, 2004.

PMID- 15955306
TI  - Connexin-based gap junction hemichannels: gating mechanisms.
AB  - Connexins (Cxs) form hemichannels and gap junction channels. Each gap junction
      channel is composed of two hemichannels, also termed connexons, one from each of
      the coupled cells. Hemichannels are hexamers assembled in the ER, the Golgi, or a
      post Golgi compartment. They are transported to the cell surface in vesicles and
      inserted by vesicle fusion, and then dock with a hemichannel in an apposed
      membrane to form a cell-cell channel. It was thought that hemichannels should
      remain closed until docking with another hemichannel because of the leak they
      would provide if their permeability and conductance were like those of their
      corresponding cell-cell channels. Now it is clear that hemichannels formed by a
      number of different connexins can open in at least some cells with a finite if
      low probability, and that their opening can be modulated under various
      physiological and pathological conditions. Hemichannels open in different kinds
      of cells in culture with conductance and permeability properties predictable from
      those of the corresponding gap junction channels. Cx43 hemichannels are
      preferentially closed in cultured cells under resting conditions, but their open
      probability can be increased by the application of positive voltages and by
      changes in protein phosphorylation and/or redox state. In addition, increased
      activity can result from the recruitment of hemichannels to the plasma membrane
      as seen in metabolically inhibited astrocytes. Mutations of connexins that
      increase hemichannel open probability may explain cellular degeneration in
      several hereditary diseases. Taken together, the data indicate that hemichannels
      are gated by multiple mechanisms that independently or cooperatively affect their
      open probability under physiological as well as pathological conditions.

PMID- 15955308
TI  - Entamoeba histolytica: observations on metabolism based on the genome sequence.
AB  - The sequencing of the genome of Entamoeba histolytica has allowed a
      reconstruction of its metabolic pathways, many of which are unusual for a
      eukaryote. Based on the genome sequence, it appears that amino acids may play a
      larger role than previously thought in energy metabolism, with roles in both ATP
      synthesis and NAD regeneration. Arginine decarboxylase may be involved in
      survival of E. histolytica during its passage through the stomach. The usual
      pyrimidine synthesis pathway is absent, but a partial pyrimidine degradation
      pathway could be part of a novel pyrimidine synthesis pathway. Ribonucleotide
      reductase was not found in the E. histolytica genome, but it was found in the
      close relatives Entamoeba invadens and Entamoeba moshkovskii, suggesting a recent
      loss from E. histolytica. The usual eukaryotic glucose transporters are not
      present, but members of a prokaryotic monosaccharide transporter family are
      present.

PMID- 15955309
TI  - Entamoeba histolytica: construction and applications of subgenomic databases.
AB  - Knowledge about the influence of environmental stress such as the action of
      chemotherapeutic agents on gene expression in Entamoeba histolytica is limited.
      We plan to use oligonucleotide microarray hybridization to approach these
      questions. As the basis for our array, sequence data from the genome project
      carried out by the Institute for Genomic Research (TIGR) and the Sanger Institute
      were used to annotate parts of the parasite genome. Three subgenomic databases
      containing enzymes, cytoskeleton genes, and stress genes were compiled with the
      help of the ExPASy proteomics website and the BLAST servers at the two genome
      project sites. The known sequences from reference species, mostly human and
      Escherichia coli, were searched against TIGR and Sanger E. histolytica sequence
      contigs and the homologs were copied into a Microsoft Access database. In a
      similar way, two additional databases of cytoskeletal genes and stress genes were
      generated. Metabolic pathways could be assembled from our enzyme database, but
      sometimes they were incomplete as is the case for the sterol biosynthesis
      pathway. The raw databases contained a significant number of duplicate entries
      which were merged to obtain curated non-redundant databases. This procedure
      revealed that some E. histolytica genes may have several putative functions.
      Representative examples such as the case of the delta-aminolevulinate
      synthase/serine palmitoyltransferase are discussed.

PMID- 15955310
TI  - Entamoeba histolytica: comparative genomics of the pre-mRNA 3' end processing
      machinery.
AB  - We report here the pre-mRNA 3' end processing machinery in Entamoeba histolytica.
      Comparative analysis of the putative sequences participating in the pre-mRNA 3'
      end processing of E. histolytica genes shows similitude and differences to those
      described for yeast and human transcripts. By a genomic survey, we identified 16
      putative genes encoding for cleavage/polyadenylation factors in this parasite. E.
      histolytica pre-mRNA 3' end processing machinery does not seem to contain
      homologous genes coding for human Symplekin, CFIm59, and CFIm68 proteins, neither
      sequences related to yeast Pta1p and Hrp1p. Protein sequence comparisons among E.
      histolytica, yeast, and human showed little variation in their functional domains
      through evolutive scale. E. histolytica pre-mRNA 3' end processing machinery
      appears to be in an intermediate evolutionary position between mammals and yeast.
      From these analyses, we propose a hypothetical working model for the pre-mRNA 3'
      end processing machinery in E. histolytica.

PMID- 15955311
TI  - Entamoeba histolytica: analysis of the trophozoite proteome by two-dimensional
      polyacrylamide gel electrophoresis.
AB  - The Entamoeba histolytica genome project carried out at TIGR and the Sanger
      Institute has produced a near-complete set of deduced open reading frame
      sequences. These data provide strong support for the identification of signals
      from proteomic analyses such as two-dimensional electrophoresis by protein
      sequencing and/or mass spectrometric methods. To carry out an initial
      investigation of the E. histolytica proteome, appropriate sample preparation and
      silver staining protocols were adapted. After preparation of protein extracts
      from E. histolytica HM-1:IMSS trophozoites, solubilized proteins were separated
      in the first dimension in IPG (immobilized pH gradient) strips depending on their
      pI and subsequently in the second dimension according to their molecular weight
      by SDS-polyacrylamide gel electrophoresis. Of the more than 1500 protein spots
      visualized, several landmark spots were isolated from the gels and identified by
      either tryptic cleavage and subsequent MALDI-TOF mass spectrometry or by protein
      sequencing.

PMID- 15955312
TI  - Genomic DNA microarrays for Entamoeba histolytica: applications for use in
      expression profiling and strain genotyping.
AB  - The parasite Entamoeba histolytica is a causative agent of dysentery and liver
      abscesses. Found predominantly in developing countries, this parasitic infection
      is responsible for significant morbidity and mortality. We have developed a
      genomic DNA microarray for E. histolytica. The array composed of 11,328 clones
      contains >2000 unique genes and was utilized for expression profiling and
      comparative genomic hybridizations of Entamoeba strains. We present a synopsis of
      our results to date and potential future applications of microarray technology
      for the study of Entamoeba biology.

PMID- 15955313
TI  - Entamoeba invadens: restriction of ploidy by colonic short chain fatty acids.
AB  - The DNA content of Entamoeba parasites appears to be regulated by an unusual
      mechanism. This conclusion, however, was based on experiments that examined
      parasites grown in media that did not contain short chain fatty acids (SCFAs)
      normally found in the colonic lumen. Since one of these SCFAs, butyrate, is known
      to affect DNA replication in eukaryotic cells, we examined the effect of SCFAs on
      Entamoeba trophozoite DNA content. Similar to reports from others, we found that
      Entamoeba invadens trophozoite cultures grown in conventional medium (TYI-S-33)
      contained cells with 2N, 4N, 8N, and 16N amounts of DNA. In contrast, cultures
      grown in TYI medium containing colonic SCFAs added in place of glucose contained
      a minor population with 2N, a major population with 4N, and very few cells with
      higher amounts of DNA. SCFAs also prevented the normal increase in the number of
      nuclei per cell in trophozoites that were induced to encyst. These results
      suggest that E. invadens trophozoite stage parasites growing in the intestine in
      the presence of high amounts of SCFAs have a ploidy range restricted to 2N/4N.
      Axenic growth of trophozoites in the absence of SCFAs, however, appears to allow
      trophozoites to increase the amount of DNA per cell, which they must do during
      the normal encystment process.

PMID- 15955314
TI  - The LINEs and SINEs of Entamoeba histolytica: comparative analysis and genomic
      distribution.
AB  - Autonomous non-long terminal repeat retrotransposons are commonly referred to as
      long interspersed elements (LINEs). Short non-autonomous elements that borrow the
      LINE machinery are called SINES. The Entamoeba histolytica genome contains three
      classes of LINEs and SINEs. Together the EhLINEs/SINEs account for about 6% of
      the genome. The recognizable functional domains in all three EhLINEs included
      reverse transcriptase and endonuclease. A novel feature was the presence of two
      types of members-some with a single long ORF (less frequent) and some with two
      ORFs (more frequent) in both EhLINE1 and 2. The two ORFs were generated by
      conserved changes leading to stop codon. Computational analysis of the immediate
      flanking sequences for each element showed that they inserted in AT-rich
      sequences, with a preponderance of Ts in the upstream site. The elements were
      very frequently located close to protein-coding genes and other EhLINEs/SINEs.
      The possible influence of these elements on expression of neighboring genes needs
      to be determined.

PMID- 15955315
TI  - Entamoeba histolytica: Characterization of human collagen type I and Ca2+
      activated differentially expressed genes.
AB  - Earlier it was demonstrated that the Entamoeba histolytica trophozoites, when
      incubated with human collagen and Ca2+, expressed and released the collagenolytic
      activity [Munoz, M.L., Calderon, J., Rojkind, M., 1982. The collagenase of
      Entamoeba histolytica. Journal of Experimental Medicine 155, 42-51], a virulence
      factor involved in the pathogenesis of amoebiasis. In this study, attempts have
      been made to identify and characterize the gene(s) that are upregulated by the
      human collagen type I and Ca2+ interaction. A comparative evaluation of gene
      expression pattern of the parasite before and after treatment with human collagen
      type I was done using the differential display reverse transcription-PCR
      technique. The cDNA fragments that were overexpressed in collagen treated
      trophozoites compared to collagen untreated trophozoites were characterized.
      Northern blot hybridization and RT-PCR amplification using gene-specific primers
      validated the differential expression. Sequence analyses and database searches
      revealed homology with known virulence factor genes of E. histolytica such as
      amoebapore C and cysteine proteinase 5, along with stress-induced protein HSP70,
      and ribosomal protein L27a (known to be involved in protein synthesis). The study
      provides the experimental evidence that interaction of E. histolytica with human
      collagen type I and Ca2+ triggers the transcriptional activation of at least two
      important genes responsible for pathogenesis of amoebiasis.

PMID- 15955316
TI  - Proteomic analysis of Gal/GalNAc lectin-associated proteins in Entamoeba
      histolytica.
AB  - Contact-dependent killing and phagocytosis of target cells by Entamoeba
      histolytica trophozoites is mediated by the galactose (Gal) and N-acetyl-d
      galactosamine (GalNAc)-inhibitable lectin. Previous work has suggested that this
      lectin functions as part of a signal transduction complex. To identify proteins
      that might be part of this complex, amebic trophozoites were bound to GalNAc-BSA
      labeled magnetic beads and lysed. Bound proteins were eluted from the beads and
      analyzed by tandem mass spectrometry. Along with the Gal/GalNAc lectin subunits,
      several cytoskeletal proteins, potential signaling proteins, and a novel
      transmembrane protein, consistently purified with the GalNAc-BSA beads.

PMID- 15955317
TI  - Entamoeba histolytica: cloning and expression of the poly(A) polymerase EhPAP.
AB  - In eukaryotes, polyadenylation of pre-mRNA 3' end is essential for mRNA export,
      stability, and translation. Here we identified and cloned a gene codifying for a
      putative nuclear poly(A) polymerase (EhPAP) in Entamoeba histolytica. Protein
      sequence alignments with eukaryotic PAPs showed that EhPAP has the RNA-binding
      region and the PAP central domain with the catalytic nucleotidyl transferase
      domain described for other nuclear PAPs. Recombinant EhPAP expressed in bacteria
      was used to generate specific antibodies, which recognized two EhPAP isoforms of
      60 and 63kDa in nuclear and cytoplasmic extracts by Western blot assays. RT-PCR
      assays showed that EhPap mRNA expression varies in multidrug-resistant
      trophozoites growing in different emetine concentrations. Moreover, EhPap mRNA
      expression is about 10- and 7-fold increased in G1 and S phase, respectively,
      through cell cycle progression. These results suggest the existence of a link
      between EhPAP expression and MDR and cell cycle regulation, respectively.

PMID- 15955318
TI  - Entamoeba histolytica: functional characterization of the -234 to -196 bp
      promoter region of the multidrug resistance EhPgp1 gene.
AB  - The multidrug resistance EhPgp1 gene is constitutively expressed in drug
      resistant trophozoites from Entamoeba histolytica. It has been demonstrated that
      two CCAAT/enhancer binding sites located in the EhPgp1 gene promoter control its
      transcriptional activation. However, functional assays of the 5' end of its
      promoter showed that region from -234 to -196 bp (38 bp) is also important for
      the EhPgp1 gene transcription. Here, we demonstrated that in the 38 bp region
      putative cis-activator sequences are located. In silico analysis showed the
      presence of GATA1, Gal4, Nit-2, and C/EBP consensus sequences. Additionally, we
      identified three specific DNA-protein complexes, which were competed by a C/EBP,
      GATA1, and HOX oligonucleotides. Finally, we partially purified three proteins of
      64.4, 56.7, and 27.4 kDa. Further investigations are currently in progress to
      determine the identity of these nuclear factors and how they are interacting with
      the EhPgp1 gene promoter.

PMID- 15955319
TI  - The diversity of Rab GTPases in Entamoeba histolytica.
AB  - Rab proteins are ubiquitous small GTP-binding proteins that form a highly
      conserved family and regulate vesicular trafficking. Recent completion of the
      genome of the enteric protozoan parasite Entamoeba histolytica enabled us to
      identify an extremely large number (>90) of putative Rab genes. Multiple
      alignment and phylogenic analysis of amebic, human, and yeast Rab showed that
      only 22 amebic Rab proteins including EhRab1, EhRab2, EhRab5, EhRab7, EhRab8,
      EhRab11, and EhRab21 showed significant similarity to Rab from other organisms.
      The 69 remaining amebic Rab proteins showed only moderate similarity (<40%
      identity) to Rab proteins from other organisms. Approximately one-third of Rab
      proteins including Rab7, Rab11, and RabC form 15 subfamilies, which contain up to
      nine isoforms. Approximately 70% of amebic Rab genes contain single or multiple
      introns, and this proportion is significantly higher than that of common genes in
      this organism. Twenty-five Rabs possess an atypical carboxyl terminus such as
      CXXX, XCXX, XXCX, XXXC, and no cysteine. We propose annotation of amebic Rab
      genes and discuss biological significance of this extraordinary diversity of
      EhRab proteins in this organism.

PMID- 15955320
TI  - Entamoeba histolytica: identification of EhGPCR-1, a novel putative G protein
      coupled receptor that binds to EhRabB.
AB  - EhRabB is an Entamoeba histolytica protein involved in phagocytosis. However,
      proteins that regulate the EhRabB activity are unknown. Here, we report the
      identification of a putative G protein-coupled receptor of E. histolytica (EhGPCR
      1) that binds to EhRabB. By two-hybrid screening, we found a 372-bp cDNA fragment
      that encodes the C-terminus of EhGPCR-1. The cloning and sequence of the full
      length cDNA revealed that it predicts a polypeptide with two tyrosine-based
      sorting signals for endocytosis and seven transmembranal domains. These results
      suggest that EhGPCR-1 could be a GPCR involved in phagocytosis. EhGPCR-1 could be
      a member of the Rhodopsin family, characterized by a short N-terminus without
      cysteine residues.

PMID- 15955321
TI  - Entamoeba histolytica: alterations in EhRabB protein in a phagocytosis deficient
      mutant correlate with the Entamoeba dispar RabB sequence.
AB  - We analyzed the expression and location of EhRabB in clone L-6, a phagocytosis
      deficient mutant of Entamoeba histolytica, in comparison with the wild-type clone
      A. Intriguingly, trophozoites of clone L-6 express more EhRabB than those of
      clone A. However, the majority of EhRabB-containing vesicles remained in the
      cytoplasm of clone L-6 during phagocytosis. To investigate molecular alterations
      in EhRabB of clone L-6 we compared the EhrabB gene sequences from clones L-6 and
      A. We also isolated, sequenced and compared the RabB protein of Entamoeba dispar.
      Results showed that EhrabB gene of clone L-6 is 98.2 and 94.1% identical to rabB
      genes of E. dispar and clone A, respectively. The rabB genes from clone A and E.
      dispar have 92.2% identity. Four out of five amino acids changes in RabB proteins
      of clone L-6 and E. dispar are shared. These changes may alter the binding of
      effector proteins and the specific subcellular location of EhRabB.

PMID- 15955322
TI  - Molecular characterization of Entamoeba histolytica RNase III and AGO2, two RNA
      interference hallmark proteins.
AB  - Entamoeba histolytica, a protozoan parasite with variable DNA content and complex
      ploidity, has defied most efforts aimed at gene depletion using classical genetic
      methods. In this study, we identified and characterized two proteins involved in
      the RNA interference (RNAi) pathway, RNase III and AGO2. Our results strengthen
      the findings that an RNAi pathway does exist in this parasite.

PMID- 15955323
TI  - A novel protease from Entamoeba histolytica homologous to members of the family
      S28 of serine proteases.
AB  - Serine proteases are one of the biologically most important and widely
      distributed enzyme families. A protease capable of degrading the substrate Suc
      AAF-AMC was isolated from axenically grown trophozoites of Entamoeba histolytica.
      The enzyme was purified by ion-exchange chromatography and electroelution, and
      appeared on 2D-PAGE as a spot of 60 kDa and pI of 4.65. Data obtained from
      zymogram suggest the active protease is present either as homodimer (130 kDa) or
      homotetramer (250 kDa). The optimal temperature of the enzyme was 37 degrees C,
      and it exhibited activity over a broad pH range. The protease was strongly
      inhibited by TPCK and chelating agents. The enzymatic activity was restored upon
      addition of calcium. BLAST analysis with the sequence of internal peptides of the
      protein revealed two open reading frames within the genome of E. histolytica,
      homologous to members of the family S28, clan SC of serine proteases.

PMID- 15955324
TI  - Entamoeba histolytica: identification and characterization of an N-ethylmaleimide
      sensitive fusion protein homologue.
AB  - Entamoeba histolytica is a phagocytic cell with numerous vesicles of different
      sizes and shapes but without a well-defined Golgi apparatus. Despite this, genes
      implied in membrane trafficking have been identified in the genome of this
      parasite. One of these genes is homologous to the N-ethylmaleimide sensitive
      fusion factor (NSF), whose protein has been shown to play an important role in
      vesicle fusion in other eukaryotic cells. In this report, we investigated the NSF
      homologue gene from a pathogenic E. histolytica, characterized its protein
      product and two of its activities, ATPase and in vitro intra-Golgi transport. The
      finding of an active NSF protein in E. histolytica indicates that a simple or
      primordial Golgi apparatus probably exists in this microorganism, as has been
      proposed by others.

PMID- 15955325
TI  - Entamoeba histolytica: structural and functional analysis of the Ehadh112 gene
      promoter.
AB  - The Entamoeba histolytica Ehcp112 and Ehadh112 genes that encode the EhCPADH
      complex are separated by a non-coding 188pb region. Their proximity suggests a
      coordinated expression regulation for both genes. Here, we studied the structure
      and function of 996 bp (p996CAT) upstream the ATG start codon of the Ehadh112
      gene. The p996CAT plasmid drove CAT transcription with a 78% of the activity
      showed by actin promoter. Deletion of 330 bp at the 5' end of p966CAT to produce
      the p776CAT plasmid, decreased activity to 40% in relation to actin promoter and
      to 50% of p996CAT, suggesting the presence of a silencer in this region.
      Interestingly, deletion of other 297 bp to the p776CAT to generate the p469CAT
      plasmid, augmented activity in 2.5-fold compared with p776CAT construction,
      showing the presence of a proximal enhancer promoter. Transcription initiation
      sites (-69 and -150 bp), TATA like box, GAAC, and Inr elements, as well as
      putative DNA binding motifs, were mapped in the -1 to -469 bp core promoter
      region.

PMID- 15955326
TI  - The Entamoeba histolytica Ehcp112 gene has a distal and weak promoter.
AB  - Ehcp112 encodes the Entamoeba histolytica EhCP112 cysteine protease that is part
      of the EhCPADH complex. By in silico analysis we identified putative
      transcription factor-binding sites along 837 bp upstream the Ehcp112 gene ATG
      codon. A TATA-like motif (TATATAAA) was located at -36 to -29 bp, a GAAC box
      (GAACC) was found at -10 to -14 bp and an Inr sequence (TTCAAC) at -8 to -2 bp.
      These tripartite promoter elements are in non-canonical positions, downstream the
      transcription initiation site (-280 bp). We cloned four Ehcp112 promoter
      fragments in pBSCAT-ACT plasmid to obtain pI (355 bp), pII (681 bp), pIII (833
      bp), and pIV (554 bp) constructs. In transfected trophozoites, only pIII drove
      CAT activity with 44% efficiency in relation to actin promoter activity. Our
      results showed the presence of a distal and weak promoter in the Ehcp112 gene.
      The active DNA region is inside the open reading frame of the Ehrab B gene,
      suggesting that expression of both genes could be coordinately regulated.

PMID- 15955327
TI  - Functional characterization of EhADH112: an Entamoeba histolytica Bro1 domain
      containing protein.
AB  - EhADH112 is part of the EhCPADH complex, a protein involved in key events of the
      Entamoeba histolytica host invasion. EhADH112 participates in trophozoite
      adherence to target cells and in phagocytosis. We report here the finding of two
      EhADH112 homologues in the E. histolytica genome (EhADH112-like proteins).
      EhADH112 and its relatives have a Bro1 domain at their amino-terminus and a
      consensus context for phosphorylation by Src-tyrosine kinases, both involved in
      signal transduction processes in other organisms. Our findings associate EhADH112
      to supplementary functions related to those reported for the Alix/AIP1 family. To
      elucidate the precise function of EhADH112, we studied the phenotypes displayed
      by trophozoites transfected with the Ehadh112 full gene. Transfected trophozoites
      overexpressed a 78 kDa protein, which was mainly targeted to the EhCPADH complex.
      Moreover, these trophozoites exhibited enhanced phagocytic rates, providing
      further evidence of EhADH112 contribution to adhesion and phagocytosis
      activities.

PMID- 15955328
TI  - Species- and strain-specific probes derived from repetitive DNA for
      distinguishing Entamoeba histolytica and Entamoeba dispar.
AB  - Entamoeba histolytica and Entamoeba dispar are two morphologically
      indistinguishable species that are found in the human gut. Of the two, E.
      histolytica is considered to be pathogenic while E. dispar is nonpathogenic. To
      generate molecular probes to detect and distinguish between the two species, we
      utilized repeat sequences present in Entamoeba genome. We have developed probes
      and primers from rDNA episomes, and unidentified Entamoeba EST1 repeat for this
      purpose, and used them for dot blot hybridization and PCR amplification. To
      investigate the possible existence of invasive and noninvasive strains of E.
      histolytica, the ability to differentiate individual isolates is necessary. For
      this purpose, we have utilized a modification of the AFLP procedure called
      'Transposon display,' which generates and displays large number of genomic bands
      associated with a transposon. We have used the abundant retrotransposon, EhSINE1,
      for this purpose,and demonstrated its potential as a marker to study strain
      variation in E. histolytica. This technique could suitably be employed in
      carrying out significant molecular epidemiological studies and large-scale typing
      of this parasite.

PMID- 15955329
TI  - Entamoeba histolytica: mechanism of decrease of virulence of axenic cultures
      maintained for prolonged periods.
AB  - Intraportal injection of non-virulent E. histolytica (derived from prolonged
      axenic culture of virulent E. histolytica) strain HM1-IMSS in normal hamsters
      results in no liver lesions and disappearance of the parasites 48-72 h after
      injection. Viability of non-virulent E. histolytica after 2 h of in vitro
      incubation in either fresh or decomplemented hamster serum is the same as control
      virulent E. histolytica (50-90%). In hamsters made leukopenic, or both
      leukopenic+hypocomplementemic, or hypocomplementemic+sephadex microspheres (to
      produce focal liver ischemia) intraportally injected non-virulent E. histolytica
      cause no lesions and disappear after 24 h. In addition, neither
      hypocomplementemia nor immunosuppression with cyclosporin A prolonged the
      survival of non-virulent E. histolytica. Methyl prednisolone treatment of
      hamsters resulted in survival of large numbers of non-virulent E. histolytica in
      the liver, with little inflammation and minimal tissue damage, for up to 7 days.
      Inflammatory cells (macrophages) would appear to be chiefly responsible for
      elimination of non-virulent E. histolytica. Parallel experiments with E. dispar
      suggest a different mechanism for its non-pathogenicity.

PMID- 15955330
TI  - Entamoeba histolytica: the serine-rich gene polymorphism-based genetic
      variability of clinical isolates from Georgia.
AB  - It is generally accepted that a majority of individuals infected by Entamoeba
      histolytica do not develop symptomatic disease. However, the parasite and the
      host factors contributing to the development of the disease, remain undetermined.
      It is also unclear why certain individuals develop extra-intestinal amebiasis
      without exhibiting apparent intestinal symptoms. An outbreak of amebic liver
      abscess in Tbilisi, Georgia in 1998-1999 suggested that the causative E.
      histolytica strain had an unusual propensity for extra-intestinal spread. To
      correlate the genetic differences with pathogenic potential of the parasite, we
      have examined the SREHP gene polymorphisms among Georgian E. histolytica
      isolates. Comparison of polymorphic patterns revealed the presence of several
      different genotypes of E. histolytica, thus preventing an association of a single
      genotype with hepatic disease, but supporting the previous finding of extensive
      genetic diversity among E. histolytica isolates from the same geographic origin.

PMID- 15955331
TI  - Entamoeba invadens: in vitro axenic encystation with a serum substitute.
AB  - The current media for axenic cultivation of Entamoeba histolytica and Entamoeba
      invadens are supplemented with bovine or equine serum, which provides several
      essential nutrients to amoebas. Serum has also been considered an essential
      component in encystation media for E. invadens. A substitute of serum, PACSR has
      been described as an alternative for growth of E. histolytica and also maintains
      growth of E. invadens. When PACSR was used instead of serum for encystation of E.
      invadens the efficiency was the same as for serum. Our present data show that
      PACSR can support the growth and induction of encystation of E. invadens strain
      IP-1.

PMID- 15955332
TI  - Comparison of two methods (microscopy and enzyme-linked immunosorbent assay) for
      the diagnosis of amebiasis.
AB  - Diagnosis of amebiasis is usually performed on a clinical basis alone in most
      endemic countries having limited economic resources. This epidemiological study
      was conducted using modern diagnostic tests for amebiasis in the southeastern
      region of Turkey, an endemic area for amebiasis. The population of this study
      included patients with symptomatic diarrhea/dysentery attending both Yuzuncu Yil
      University, Van and Harran University, Sanliurfa, Turkey. A total of 380 stool
      specimens were collected and examined for Entamoeba by light microscopy (fresh,
      lugol, and trichrome staining) and stool antigen detection based- enzyme-linked
      immunosorbent assay (EIA) test (TechLab Entamoeba histolytica II). 24% (91/380)
      of stool specimens were positive for E. histolytica/Entamoeba dispar
      trophozoites/cysts microscopically using trichrome staining. 13% (51/380) of the
      stool specimens were found to be positive for E. histolytica by the EIA test,
      including 15% (14/91) of microscopy (+) stool specimens and 13% (37/289) of
      microscopy (-) stool specimens. Enteric parasites were common in these
      populations with 66% (251/380) of the study population harboring more than one
      parasite. In addition to the 13% (51/380) of patients determined to have E.
      histolytica by EIA, eighty-six patients (22.6%) had Blastocystis hominis, 54
      (14.2%) Entamoeba coli, 44 (11.5%) Giardia lamblia, 16 (4.2%) Chilomastix
      mesnili, 15 (3.9%) Iodamoeba butschlii, 12 (3.1%) Hymenolepis nana, 9 (2.3%)
      Endolimax nana, 9 (2.3%) Dientamoeba fragilis, and 8 (2.1%) had Ascaris
      lumbricoides. We concluded that E. histolytica infection was found in 13% of the
      patients presenting with diarrhea in Van and Sanliurfa Turkey.

PMID- 15955333
TI  - Entamoeba histolytica and Entamoeba dispar: prevalence infection in a rural
      Mexican community.
AB  - The frequency of Entamoeba histolytica and Entamoeba dispar infection was
      analyzed in a rural community in the state of Morelos, Mexico, through PCR
      technique by using specie specific primer. The E. histolytica specie was detected
      in 33 of 290 analyzed stool samples (11.4%), E. dispar specie was observed in 21
      samples (7.2%) and both species of Entamoeba were detected in seven samples
      (2.4%). So a higher E. histolytica than E. dispar frequency infection was
      detected (13.8 versus 9.6%). Even though in our design we did not considered the
      follow-up of included individuals, the absence of invasive amebiasis cases in the
      studied population during our stay in town was unexpected.

PMID- 15955334
TI  - Entamoeba histolytica and/or Entamoeba dispar: infection frequency in HIV+/AIDS
      patients in Mexico city.
AB  - The objective of this work was to evaluate the frequency of Entamoeba
      histolytica/Entamoeba dispar intestinal infection in HIV+/AIDS subjects and their
      HIV- close relatives or sexual partners. Enteric parasites were investigated in
      stool samples by microscopic examination and E. histolytica and E. dispar were
      identified by PCR. We found by microscopic analysis in HIV+/AIDS group that the
      E. histolytica/E. dispar complex was present in 5.9% of the members, while in the
      HIV- group was 2.9%. With PCR we found that the E. histolytica prevalence was
      25.3% in the HIV+/AIDS group and 18.5% in the HIV-group. The difference in the
      results obtained with the microscopic and PCR is due to the different sensibility
      of the procedures. Besides, we found patients who were infected with E.
      histolytica in both groups were asymptomatic cyst passers. Our results suggest
      that E. histolytica strains prevalent in the studied community appear to be of
      low pathogenic potential.

PMID- 15955335
TI  - Effect of high temperature and water stress on in vitro germination and growth in
      isolates of the entomopathogenic fungus Beauveria bassiana (Bals.) Vuillemin.
AB  - In non-irrigated agricultural fields in tropical zones, high temperature and
      water stress prevail during the main cropping season. Natural epizootics of
      Beauveria bassiana on lepidopteran pests occur during winter. Application of B.
      bassiana during hot months when pest populations are at their climax may prove an
      effective management strategy. Therefore, 29 isolates of B. bassiana were tested
      for their ability to germinate and grow in temperature and water availability
      conditions prevailing during the pest season in these fields. The effect of
      temperature cycles with 8 h duration of high temperature fluctuating with 16 h
      duration of lower temperature (similar to field conditions); low water
      availability; and a combination of these two stress conditions was studied.
      Germination and growth assays were done at fluctuating temperature cycles of 32,
      35, 38, and 42+/-1 degrees C (8 h)/25+/-1 degrees C (16 h) and in media with
      water stress created by 10, 20, 30, and 40% polyethylene glycol (PEG 6000).
      Assays set at a continuous temperature of 25+/-1 degrees C with no PEG in the
      medium served as controls. Stress was assessed as percentage germination or as
      growth relative to control. Isolates showing 90% growth relative to the control
      at temperature cycles including high temperatures of 35 and 38+/-1 degrees C were
      identified. One isolate (ARSEF 2860) had a thermal threshold above 43 degrees C.
      At 25 degrees C, all but one isolate of B. bassiana showed >90% growth relative
      to the control in 10% PEG (-0.45 MPa). Some isolates were found with >90% growth
      relative to control in medium having 30% PEG with water availability (1.33 MPa),
      nearly equivalent to that in soils which induce permanent wilting point of
      plants. When isolates that showed >90% growth relative to the control at both
      stress conditions, were stressed simultaneously, a decrease in growth was
      observed. Growth was reduced by approximately 20% at 35+/-1 degrees C (8 h)/25+/
      1 degrees C (16 h) and 10% PEG and was affected to a greater degree in
      combinations of harsher stress conditions. The isolate ARSEF 2860 with a thermal
      threshold of >43 degrees C showed approximately 80% relative growth at a combined
      stress of 38+/-1 degrees C (8 h)/25+/-1 degrees C (16 h) and 10% PEG. These
      findings will aid the selection of isolates for use in field trials in hot or dry
      agricultural climates.

PMID- 15955336
TI  - Genotypic variation and presence of rare genotypes among Douglas-fir tussock moth
      multicapsid nucleopolyhedrovirus (OpMNPV) isolates in British Columbia.
AB  - The Douglas-fir tussock moth (Orgyia pseudotsugata) multicapsid
      nucleopolyhedrovirus (OpMNPV) is periodically applied to suppress Douglas-fir
      tussock moth populations in British Columbia and in the western United States.
      The strain of OpMNPV in the product currently used for suppression is not
      genetically distinct from naturally occurring OpMNPV. To separate the mortality
      caused by the applied virus from that caused by the naturally occurring virus, a
      rare and genetically distinct strain of OpMNPV must be applied. To learn more
      about the genotypic diversity of OpMNPV populations in BC and to identify rare
      strains in this region, viral DNA was extracted from larvae reared from 208 field
      collected egg masses found in five geographic regions of British Columbia and
      subjected to REN analysis. Nine, 12, and 9 different genotypes were detected
      using PstI, SalI, and HindIII, respectively. When the PstI, SalI, and HindIII
      profiles for each pure (single strain) isolate were grouped and considered as a
      combined PstI-SalI-HindIII genotype, 23 different genotypes were identified among
      185 isolates. Nine rare OpMNPV genotypes were selected as ideal candidates for
      use as a potential 'marker strain' to accurately determine the efficacy of the
      treatment.

PMID- 15955337
TI  - First report of three protozoan parasites (a haplosporidian, Marteilia sp. and
      Marteilioides sp.) from the Manila clam, Venerupis (=Ruditapes) philippinarum in
      Japan.
AB  - Recently, natural stocks of the Manila clam, Venerupis (=Ruditapes)
      philippinarum, have been drastically reduced in Japan. To clarify the reason for
      this decline in number, clams were sampled monthly from Yamaguchi and processed
      for histological observations, during which three protozoan parasites were
      discovered. Transmission electron microscopy revealed that these parasites were
      unidentified haplosporidian in the connective tissues, Marteilia sp. in the
      digestive gland and Marteilioides sp. in the oocytes. Histopathological
      observations suggest that Marteilia sp. and Marteilioides sp. were not pathogenic
      to the host. However, infection with a haplosporidian may have a negative impact
      on the clams. The prevalence of these parasites was low and further
      investigations should be undertaken to clarify their taxonomic status and
      establish any pathogenicity to clams.

PMID- 15955338
TI  - Oral toxicity of Photorhabdus toxins against thrips species.
AB  - The oral toxicity of excretion products of several Photorhabdus and Xenorhabdus
      strains was tested on two thrips species: Frankliniella occidentalis and Thrips
      tabaci. Out of 46 Photorhabdus isolates and six Xenorhabdus isolates only six
      North American P. temperata isolates were toxic to the thrips species. After 7
      days of drinking from P. temperata supernatant a mortality of 90% could be
      reached. Thrips were also killed after sucking from leaves covered with the
      toxins. Toxins have a negative effect on thrips fecundity. Possibilities of using
      P. temperata in the control of thrips will be discussed.

PMID- 15955339
TI  - Mass harvesting of the entomopathogenic fungus, Neozygites fresenii, from natural
      field epizootics in the cotton aphid, Aphis gossypii.
AB  - Epizootics caused by insect pathogens sometimes occur over wide areas and result
      in millions of infected insects. Naturally infected insects can be considered a
      natural resource for harvesting insect pathogens. We developed methods to mass
      harvest the fungal pathogen Neozygites fresenii (Entomophthorales: Neozygitaceae)
      from epizootics in Aphis gossypii (Homoptera: Aphididae) in a commercial cotton
      field in Arkansas. A total of 30,722 aphids infected with N. fresenii in the
      mature hyphal body or early conidiophore stages were harvested, dried, and
      frozen. Three desiccants were compared: silica gel, dry rock salt, and wet rock
      salt. Silica gel was the superior material because it more rapidly and thoroughly
      dried cotton leaves and aphids. Using this method a mean of 193.4 infected aphids
      could be harvested per hour from cotton leaves dried over silica gel. The quality
      of harvested infected aphids was high and resulted in a mean of 70.4% sporulation
      from infected aphids harvested from the silica gel desiccant.

PMID- 15955340
TI  - Tropical soil microflora of spice-based cropping systems as potential antagonists
      of root-knot nematodes.
AB  - Suppression of plant parasitic nematodes with nematode predators, parasites or
      antagonists is an eco-friendly approach than the toxic chemicals. In a study,
      soil borne fungi from the rhizosphere of major spice crops were collected from
      diverse cropping systems prevailing in three southern states of India. A series
      of in vitro studies were conducted using 73 freshly collected fungal isolates and
      76 isolates obtained from other sources. Out of this 67 isolates were not
      parasitic on females of root-knot nematodes whereas 115 isolates, though
      colonized the egg masses, did not show any signs of parasitism on nematode eggs.
      Fifty-nine isolates showed 50-90% inhibition in egg hatch. Pochonia
      chlamydospora, Verticillium lecanii, Paecilomyces lilacinus, and few isolates of
      Trichoderma spp. showed >25% parasitism on root-knot nematode eggs. The most
      promising isolates in this study were one isolate each of Aspergillus (F.45),
      Fusarium (F.47), and Penicillium (F.59); three each isolates of Trichoderma (F.3,
      F.52, and F.60) and Pochonia (F.30 and Vc.3) Verticillium (Vl); and two isolates
      of fungi that could not be identified (F.28 and F.62). Parasitism by Aspergillus
      tamarii, Aspergillus ustus, Drechslera sp., Humicola sp., and Scopulariopsis sp.
      on root-knot nematode eggs or females, reported in the present study, are new
      reports.

PMID- 15955341
TI  - First record of entomopathogenic nematodes (Steinernematidae and
      Heterorhabditidae) in Costa Rica.
AB  - A survey of entomopathogenic nematodes was conducted in the north Pacific
      (Guanacaste Conservation Area) and southeast Caribbean (Gandoca-Manzanillo
      Natural Refuge) regions of Costa Rica. Out of a total of 41 soil samples, 5 were
      positive for entomopathogenic nematodes (20.5%), with 3 (12.3%) containing
      Steinernema and 2 (8.2%) Heterorhabditis isolates. Morphological and molecular
      studies were undertaken to characterize these isolates. The Heterorhabditis
      isolates were identified as Heterorhabditis indica and the three Steinernema
      isolates were identified as two new undescribed species. H. indica was recovered
      from a coastal dry forest. Steinernema n. sp. 1 was isolated from a rainforest
      valley, between volcanoes. Steinernema sp. n. 2 was isolated from sand dunes in
      the Caribbean Coast (Punta Uva) near the rainforest strip along the coast.
      Although limited to two geographic regions, this study suggests entomopathogenic
      nematodes may be diverse and perhaps widely distributed in Costa Rica. A more
      intensive survey, covering all geographic regions is currently undergoing.

PMID- 15955342
TI  - Solenopsis invicta virus-1A (SINV-1A): distinct species or genotype of SINV-1?
AB  - We have cloned and sequenced a 2845 bp cDNA representing the 3'-end of either a
      new picorna-like virus species or genotype of Solenopsis invicta virus-1 (SINV
      1). Analysis of the nucleotide sequence revealed 1 large open reading frame. The
      amino acid sequence of the translated open reading frame was most identical to
      structural proteins of SINV-1 (97%), followed by the Kashmir bee virus (KBV,
      30%), and acute bee paralysis virus (ABPV, 29%). A PCR-based survey for SINV-1
      and the new species or genotype (tentatively named S. invicta virus-1A, SINV-1A)
      using RNA extracts of S. invicta collected around Gainesville, Florida, revealed
      a mean colony infestation rate of 25% by SINV-1 and 55% by SINV-1A. Both SINV-1
      and SINV-1A were found to co-infect 17.5% of the nests surveyed. Although the
      data preclude definitive species or genotype assignment, there is no doubt that
      SINV-1A is distinct from SINV-1, identifiable, and infects S. invicta. We provide
      a simple RT-PCR technique capable of discerning SINV-1 and SINV-1A infection of
      S. invicta.

PMID- 15955343
TI  - Characterization and polyhedrin gene cloning of Lymantria xylina multiple
      nucleopolyhedrovirus.
AB  - A baculovirus has been isolated from infected larvae of the casuarina moth,
      Lymantria xylina Swinehoe (Lepidoptera: Lymantriidae) in Taiwan. Ultrastructural
      observation revealed that this virus is a multiple nucleopolyhedrovirus (MNPV),
      and the name L. xylina MNPV (LyxyMNPV) was proposed. Restriction endonuclease
      (BamHI, EcoRI, and EcoRV) profiles of LyxyMNPV genome differed from those of
      other known NPVs. The size of the LyxyMNPV genome was estimated to be 154+/-1.26
      kbp (mean+/-SE). The polyhedrin gene is located in the BamHI-D, EcoRI-C, and
      EcoRV-K fragments of LyxyMNPV genome. The gene organization of the LyxyMNPV EcoRV
      K fragment and the phylogenetic analysis based on the polyhedrin gene sequences
      showed that LyxyMNPV is closely related to the L. dispar MNPV (LdMNPV).
      Furthermore, a rapid assay method was developed to distinguish LyxyMNPV from
      LdMNPV based on PCR-RFLP (polymerase chain reaction-restriction fragment length
      polymorphism) analysis of polyhedrin genes.

PMID- 15955344
TI  - Multiple symbiotes in larval black flies (Diptera: Simuliidae): associations of
      trichomycete fungi with ichthyosporeans, mermithid nematodes, and microsporidia.
AB  - Studies of the interactions between two or more species of symbiotic
      microorganisms in a single host animal have lagged behind those involving
      interactions between hymenopteran or dipteran parasitoids. We screened the larvae
      of four species of black flies (Cnephia ornithophilia, Simulium furculatum,
      Simulium innoxium, and Simulium vandalicum) to determine if the colonization and
      prevalence of trichomycete fungi were influenced by ichthyosporeans, mermithid
      nematodes, microsporidia, or other species of trichomycetes. Differences in the
      layering of the peritrophic matrix of microsporidian-infected larvae, compared
      with that of uninfected larvae, were associated with greater levels of
      colonization by the midgut-inhabiting trichomycete Harpella melusinae.
      Colonization levels of different species of trichomycetes were significantly
      correlated with one another in only 2 of 11 cases. Aside from the consistent
      attachment of the trichomycete Simuliomyces microsporus to the ichthyosporean
      Paramoebidium chattoni, we found little evidence that prevalence and colonization
      levels of trichomycetes were influenced by other symbiotes, including other
      trichomycetes. This trend might reflect the physical separation of trichomycetes,
      which are gut specific, from other symbiotes. In addition, any combinations of
      symbiotes that were wholly incompatible would not have been observed in our field
      collected material.

PMID- 15955345
TI  - Impact of the entomopathogenic fungus Verticillium lecanii on development of an
      aphid parasitoid, Aphidius colemani.
AB  - The parasitoid Aphidius colemani developed normally (approximately 90% adult
      emergence) when its cotton aphid (Aphis gossypii) host was treated with
      Verticillum lecanii conidia 5 or 7 days after parasitization. Fungus exposure 1
      day before or up to 3 days after parasitization, however, reduced A. colemani
      emergence from 0 to 10%. Also, numbers of spores and mycelial fragments in aphid
      homogenates were much higher in aphids exposed to the fungus up to 3 days after
      parasitization than in aphids treated after 5 or 7 days. Our results suggest that
      the parasitoid and fungus may be used together for aphid biocontrol as long as
      fungus applications are timed to allow late-instar development of the parasitoid.

PMID- 15955346
TI  - DNA isolation from museum and type collection slides of microsporidia.
AB  - DNA from 19 species of microsporidia was isolated and amplified from infected
      host tissue that were originally prepared between the years 1946 and 1996. The
      smears, on glass microscope slides, were either Giemsa-stained or unstained.
      Methanol-fixed, Giemsa-stained smears proved to be suitable for DNA isolation;
      DNA was amplified from only two of 14 unstained slides. The isolated DNA was
      successfully amplified in PCRs using small subunit and large subunit rDNA primers
      and sequenced. The high efficiency of DNA isolation demonstrates the usefulness
      of archival and type collection slides for some molecular biology and molecular
      taxonomy studies.

PMID- 15955347
TI  - Effect of Gregarina sp. parasitism on the susceptibility of Blattella germanica
      to some control agents.
AB  - Gregarines are enteric parasites of invertebrates but little is known about the
      negative effects of this parasitism on host species. The present study evaluates
      the influence of the parasitism of Gregarina sp. on the survival of Blattella
      germanica and methods for elimination of gregarine infection in laboratory
      rearing systems. Insects were dissected and the infection was detected in 80% of
      a sample of 50 adults. Diseased cockroaches had swollen abdomens, slower movement
      at high incidences of the protozoan, and short antennas. Dead cockroaches showed
      darkened body and putrid smell, indicating septicaemia. Infected insects were
      more susceptible than healthy cockroaches when treated with Metarhizium
      anisopliae and triflumuron.

PMID- 15955348
TI  - Apoptotic processes during mammalian preimplantation development.
AB  - The paper provides a review of the current state of knowledge on apoptosis during
      normal preimplantation development based on the literature and on the authors'
      own findings. Information is focused on the occurrence and the characteristics of
      spontaneous apoptotic processes. Reports concerning the chronology and the
      incidence of programmed cell death in mouse, cow, pig and human embryos in early
      preimplantation stages up to the blastocyst stage are summarized. In addition,
      specific attributes of the apoptotic process in mammalian preimplantation
      development are provided, including the description of both morphological and
      biochemical features of cell death.

PMID- 15955349
TI  - Relationship between non-return rate and chromatin condensation of deep frozen
      bull spermatozoa.
AB  - This study analyzes the relationship between chromatin condensation and field
      fertility, expressed as 90 days non-return rate (NRR), of bulls actively used by
      AI studs. Frozen-thawed semen from five bulls (six ejaculates per bull, three
      straws per ejaculate), that showed a non-return rate between 60 and 80%, were
      analyzed to assess sperm chromatin condensation and stability. The chromatin
      condensation was determined by flow cytometry using propidium iodide as
      fluorochrome, and the chromatin stability was evaluated by inducing its
      decondensation with SDS and EDTA. Coefficient of variation among replicates was
      less than 7% and 5% for chromatin condensation and stability, respectively. No
      correlation was present between chromatin condensation and NRR. However,
      significant correlation was found between chromatin stability and NRR. Chromatin
      stability was higher (P < 0.05) in those bulls that showed higher fertility. The
      results obtained in this study conclude that assessment of stability could be a
      valuable tool for routine evaluation and identification of ejaculates with high
      levels of sperm chromatin abnormalities and to detect animals of higher
      reproductive potential.

PMID- 15955350
TI  - Factors affecting gestation duration in the bitch.
AB  - A retrospective analysis was performed to determine the effects of age, breed,
      parity, and litter size on the duration of gestation in the bitch. Bitches at two
      locations were monitored from breeding to whelping. A total of 764 litters
      whelped from 308 bitches (36 large hounds, 34 Golden Retrievers, 23 German
      Shepherd Dogs (GSD), and 215 Labrador Retrievers). By breed, the number of
      whelpings was 152, 72, 58, and 482 for the hounds, Golden Retrievers, German
      Shepherd Dogs, and Labrador Retrievers, respectively. Whelping was predicted to
      be 57 d from the first day of cytologic diestrus in the hounds or 65 d from the
      initial progesterone rise in the other breeds. The average gestation duration
      (calculated as 8 d prior to Day 1 of cytologic diestrus in hounds or measured
      from the initial progesterone rise in other breeds) by breed (days +/- S.D.) was
      66.0 +/- 2.8, 64.7 +/- 1.5, 63.6 +/- 2.1, and 62.9 +/- 1.3 for the hounds, Golden
      Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. The
      relationship of age, breed, parity, and litter size with the difference in
      gestation duration was evaluated using log linear modeling. Age or parity had no
      effect on gestation duration. Compared to Labrador Retrievers, the German
      Shepherd Dogs, Golden Retrievers and hounds were more likely to have a longer
      gestation duration; three, four and nearly eight times as likely, respectively.
      Bitches whelping four or fewer pups were significantly more likely to have a
      longer gestation duration than those whelping five or more pups; the prolongation
      averaging 1 d.

PMID- 15955351
TI  - Effect of solid storage at 15 degrees C on the subsequent motility and fertility
      of rabbit semen.
AB  - We conducted two studies to improve preservation of rabbit semen. The objective
      of the first study was determine whether a glucose- and fructose-based extender
      with two different amounts of gelatin would solidify at 15 degrees C, and to
      evaluate the influence of gelatin supplementation on sperm motility parameters
      after storing semen up to 10 days at 15 degrees C. The fertility of rabbit semen
      diluted in the best gelatin-supplemented extender established in Study 1 and
      stored for up to 5 days was evaluated in the second study. In Study 1, semen was
      collected with an artificial vagina from 40 bucks. Each ejaculate was diluted to
      (80-100) x 10(6) spermatozoa/mL (1:3, semen/extender) at 37 degrees C in one of
      the three following glucose- and fructose-based extenders: control (standard
      liquid extender), semi-gel or gel (0.7 or 1.4 g gelatin in 100 mL extender,
      respectively). Pools of semen were allocated among 0.6 mL plastic artificial
      insemination (AI) guns. Thirty (10 per extender group) AI doses were immediately
      analyzed (0 h) and the remainder stored in a refrigerator (15 degrees C) for 12,
      24, 36, 48, 72, 96, or 240 h. All doses with gelatin extenders solidified at 15
      degrees C. Semen samples, prewarmed to 37 degrees C, were evaluated with a
      computer-assisted sperm analysis (CASA) system. The percentage of motile cells
      was significantly lower using the liquid compared to the gel extenders during
      semen storage from 0 to 96 h. Although significance was lost, these differences
      persisted after 240 h of storage. Motility of spermatozoa in the semi-gel
      extender was intermediate between that of liquid and gel extender throughout the
      study. Study 2 was performed on 1250 multiparous lactating does. Five homogeneous
      groups of 250 does previously synchronized were inseminated using semen
      previously stored for 120, 96, 72, 48 or 24 h, respectively. Rabbit does
      receiving 24 h-stored semen (diluted with the control extender used in Study 1)
      served as controls. The remaining females received seminal doses supplemented
      with 1.4 g/100mL gelatin (gel extender used in Study 1). Kindling rates for
      rabbit does inseminated with gelatin-supplemented (solid) semen doses stored for
      48 h (88%) or 72 h (83%) were similar to those recorded for liquid controls
      stored for 24 h (81%), whereas rates significantly decreased when the semen was
      solid and stored for 96 h (64%) or 120 h (60%) before AI. In conclusion, rabbit
      spermatozoa were effectively stored in the solid state at 15 degrees C, with
      fertility preserved for up to 5 days. Solid storage of rabbit semen would
      facilitate commercial distribution.

PMID- 15955352
TI  - Role of cumulus cells during maturation of porcine oocytes in the rise in
      intracellular Ca2+ induced by inositol 1,4,5-trisphosphate.
AB  - At the time of fertilization, release of inositol 1,4,5-trisphosphate (IP3) into
      the cytoplasm of oocytes is said to be induced by hydrolysis of
      phosphatidylinositol bis phosphate (PI2) via activation of phospholipase C and is
      responsible for the Ca2+ oscillation in oocytes immediately after sperm
      penetration. On the other hand, cumulus cells have been reported to play an
      important role in cytoplasmic maturation of mammalian oocytes and to affect
      embryonic development after fertilization. To obtain more information on the role
      of cumulus cells in cytoplasmic maturation of oocytes, the effects of cumulus
      cells on the rise in [Ca2+]i and the rates of activation and development of
      porcine mature oocytes induced by IP3 injection were investigated. Mature porcine
      oocytes that had been denuded of their cumulus cells in the early stage of the
      maturation period had a depressed rise in [Ca2+]i (4.0-6.0) and reduced rates of
      activation (31.4-36.8%) and development (10.0-24.4%) induced by IP3 injection
      compared with those of their cumulus-enclosed counterparts (7.3, 69.1% and 43.8%;
      P < 0.05). The [Ca2+]i rise and the rates of activation and development depressed
      by the removal of cumulus cells were restored by adding pyruvate to the
      maturation medium. Furthermore, the IP3 injection-induced depression of [Ca2+]i
      rise in mature oocytes derived from cumulus-denuded oocytes (DOs) was restored
      when they were cultured in a medium with pyruvate (3.9-6.3, P < 0.05). Also,
      mature oocytes from cumulus-oocyte complexes (COCs) cultured in a medium without
      glucose had a lower rise in [Ca2+]i than that in mature oocytes from COCs
      cultured with glucose (7.4-6.0, P < 0.05). Cumulus cells supported porcine
      oocytes during maturation in the rise in [Ca2+]i induced by IP3 and the following
      activation and development of porcine oocytes after injection of IP3. Moreover,
      we inferred that a function of cumulus cells is to produce pyruvate by
      metabolizing glucose and to provide oocytes with pyruvate during maturation,
      thereby promoting oocyte sensitivity to IP3.

PMID- 15955353
TI  - SNARE proteins and caveolin-1 in stallion spermatozoa: possible implications for
      fertility.
AB  - Proteins implicated in the "SNARE hypothesis" for membrane fusion have been
      characterized in the acrosome of several mammalian species, and a functional role
      for these proteins during the acrosome reaction has been proposed. We have
      investigated the presence of SNAREs in equine sperm, using semen samples obtained
      from stallions with varying fertility. Immunocytochemical analysis revealed that
      members of different SNARE families can be detected on the acrosome of equine
      sperm, notably in the acrosomal cap and equatorial segment. These proteins
      include the t-SNARE syntaxin, the v-SNARE synaptobrevin/VAMP, the calcium sensor
      synaptotagmin, and the ATPase NSF. Also present is caveolin-1, a component of
      lipid rafts. Stallions with fertility problems presented the worst quality of
      sperm and acrosomal membrane, and had less sperm cells stained positively for
      SNAREs and caveolin-1, than sperm from fertile donors (p < 0.001). Ubiquitin
      surface staining was also performed and it seemed to inversely correlate with
      stallion fertility, supporting data obtained with the negative staining
      technique. A male-related problem was confirmed when mares that had failed to
      impregnate with samples from an infertile stallion were successfully inseminated
      with sperm from a fertile donor. Furthermore NSF, synaptotagmin and caveolin-1
      staining seemed to be useful in predicting stallion fertility, i.e. significantly
      more sperm cells stained positively for these proteins in samples from fertile
      males. Although these results need to be expanded on a larger scale, they suggest
      that acrosomal and surface staining of equine sperm with novel probes may
      constitute useful tools in predicting stallion fertility.

PMID- 15955354
TI  - Incidence of spontaneous ovulation and development of the corpus luteum in non
      mated dromedary camels (Camelus dromedarius).
AB  - The occurrence of spontaneous ovulation in dromedaries was examined in two
      separate studies including 20 non-lactating, barren and 12 lactating dromedaries,
      respectively. Lactating camels were milked twice a day with an automatic bucket
      milking machine. Ovarian activity was monitored by repeated ultrasonography.
      Blood samples for progesterone were collected daily or two to three times a week.
      To compare CL development after spontaneous and induced ovulations, ovulation was
      induced by a GnRH analogue in eight lactating dromedaries. Spontaneous ovulation
      was observed in one non-lactating camel (1 of 20 camels, 5%; 1 of 70 follicular
      waves, 1.4%), whereas, spontaneous ovulation was detected more frequently in
      lactating dromedaries (5 of 12 camels, 41.7%; 13 of 91 follicular waves, 14.3%).
      In one lactating camel, spontaneous ovulation occurred repeatedly for nine times.
      There was a significant effect of type of ovulation (spontaneous versus induced,
      P < 0.05) and day (P < 0.001) on serum progesterone concentration. Mean serum
      progesterone levels and total progesterone production (AUC) were higher after
      induced ovulation. Luteal diameter and serum progesterone concentration were
      positively correlated (r = 0.71, P < 0.001), but there was a significant
      difference between morphological and functional development of the CL. In
      dromedaries, morphological development starts earlier, morphological regression
      starts later and last longer than functional development and regression of the
      CL. Compared to induced ovulation, functional development of the CL after
      spontaneous ovulation might be altered but the morphological development is not
      affected.

PMID- 15955355
TI  - Does multivariate analysis of post-thaw sperm characteristics accurately estimate
      in vitro fertility of boar individual ejaculates?
AB  - The objective of this study was to determine if a multivariate pattern analysis
      of frozen-thawed sperm characteristics of boar semen of unknown fertility, thus
      identifying groups of ejaculates as "good" or "bad" freezers, would estimate
      their fertilizing potential in an in vitro embryo production (IVP) system. Frozen
      thawed spermatozoa from a single ejaculate collected from 46 boars were evaluated
      for sperm motility and kinematic patterns, for sperm viability and for early
      changes in sperm membrane stability. All data generated were used for a
      multivariate pattern analysis (PATN; CSIRO, Canberra, Australia) which
      objectively classified all ejaculates within a data set in to one of two groups,
      categorised as "good" (n = 25) or "bad" (n = 21) according with their
      freezability. In vitro matured oocytes were exposed to 2000 or 4000 frozen-thawed
      spermatozoa per oocyte for 6h and then cultured in embryo culture medium for
      either 6h (assurance of fertilization) or 7 days (to collect data on embryo
      development). Rates of sperm oocyte penetration and of embryo development
      significantly (p < 0.05) increased in a sperm:oocyte ratio-dependent manner. A
      similar pattern was observed when sperm characteristics were grouped. Indeed,
      ejaculates classified as "good" showed significantly (p < 0.05) higher rates of
      oocyte penetration, cleavage and of blastocyst formation than those classified as
      "bad". However, variation was still present among individuals (ejaculates, boars)
      in their ability to produce blastocysts in vitro. It is therefore concluded that
      despite the presence of a relationship for ejaculates with good semen quality
      post-thaw (thus grouped as "good") to higher IVP-results, the presence of
      individual variation does not allow for an accurate estimation of in vitro
      fertility based solely on the frozen-thawed semen quality parameters of a single
      ejaculate from a given boar.

PMID- 15955357
TI  - Growth and fertility of bulls cloned from the somatic cells of an aged and
      infertile bull.
AB  - In the present study, somatic cell cloning technology was used to produce eight
      newborn calves from an aged, infertile bull. Average birth weight of these calves
      was significantly higher than that of calves produced using AI. Four of the
      cloned calves died during the peripartum period; the remaining four (Clones A-D)
      survived and were used in this study. Two of the surviving calves (Clones C and
      D) were castrated; growth rates of the intact and castrated clones were similar
      to those of intact and castrated bulls, respectively, that had been derived by
      AI. Both uncastrated bulls (Clones A and B) began to produce normal semen at
      approximately 12 months of age. Semen produced by these clones, and their nuclear
      donor, was subsequently used for IVF; the proportion of IVM-IVF oocytes
      developing to the blastocyst stage was 23.4% (50/214), 28.4% (52/183) and 30.9%
      (63/204), respectively. Conception rates for AI were 54.5% (12/22) and 62.7%
      (64/102) for semen derived from Clone A and from the nuclear donor, respectively.
      The length of pregnancy and birth weight of the calves derived from semen
      collected from clones were similar to those of calves obtained by conventional AI
      using semen from their nuclear donor. Therefore, sires cloned from the somatic
      cells of an aged and infertile bull had normal fertility.

PMID- 15955356
TI  - Bovine oocyte vitrification before or after meiotic arrest: effects on
      ultrastructure and developmental ability.
AB  - The nuclear stage at which oocytes are cryopreserved influences further
      development ability and cryopreservation affects ultrastructure of both cumulus
      cells and the oocyte. In this work, we analyze the effects of vitrification at
      different nuclear and cytoplasmic maturation stages on the oocyte ultrastructure
      and developmental ability. Culture in TCM199 + PVA with roscovitine 25 M during
      24h led to meiotic arrest (MA) in cumulus-oocyte complexes (COCs), while
      permissive in vitro maturation (IVM) was performed in TCM199, 10% FCS, FSH-LH and
      17beta-estradiol for 24 h. Oocytes were vitrified using the open pulled straw
      method (OPS) with minor modifications. Fresh and vitrified/warmed COCs were fixed
      as immature, after IVM, after meiotic arrest (MA) and after MA + IVM.
      Vitrification combined with MA followed by IVM produced the highest rates of
      degeneration, regardless of the vitrification time. As a consequence, lower
      proportions of embryos cleaved in these groups, although differences were
      eliminated at the five-eight cell stage. Development rates up to day 8 were
      similar in all experimental groups, being significantly lower than those in fresh
      controls. Only oocytes vitrified after IVM were able to give blastociysts. The
      morphological alterations observed can be responsible for compromised
      development. More research is needed to explain the low survival rates of the
      bovine oocyte after vitrification and warming.

PMID- 15955358
TI  - Efficacy of either a single or split treatment of PGF2alpha after a 14 day
      melengestrol acetate treatment to synchronize estrus and induce luteolysis in Bos
      indicus x Bos taurus heifers.
AB  - Two experiments evaluated a modified delivery of prostaglandin F2alpha
      (PGF2alpha) after a melengestrol acetate (MGA) treatment in Angus and Bos indicus
      x Bos taurus (BI) heifers. Experiment 1 was replicated three times with yearling
      BI heifers (n = 695). Heifers received MGA (0.5 mg head(-1) day(-1)) for 14 days.
      In Replications 1 and 2, heifers received either 25 mg of PGF2alpha im 19 days
      after MGA (single) or 12.5 mg of PGF2alpha im 19 and 20 days after MGA (split).
      In Replication 3, heifers received the same treatments, with PGF2alpha initiated
      either 18 or 19 days after MGA. Estrus was detected for 72 h after PGF2alpha,
      with AI commencing 8-12 h after a detected estrus. Heifers not observed in estrus
      by 72 h were timed-AI concomitant with GnRH (100 microg im). Heifers from
      Replication 2 (n = 146) had blood samples collected at the initial PGF2alpha and
      at timed-AI to determine corpus luteum (CL) regression by evaluating plasma
      progesterone concentrations. The interval from MGA withdrawal to PGF2alpha did
      not have a significant effect on any variable in Replication 3 and there were no
      treatment by replication effects for any variables, therefore data were pooled.
      Modifying the PGF2alpha treatment from a single treatment to two treatments on
      consecutive days increased (P < 0.05) 72 h estrous response (43.2% versus 50.1%),
      timed-AI (23.9% versus 33.5%) and total-AI pregnancy rates (34.5% versus 42.5%),
      and CL regression (79.1% versus 92.5%), respectively. In Experiment 2, yearling
      Angus (n = 66) and 2-year-old BI (n = 68) heifers were synchronized as per
      Experiment 1 (with the initial PGF2alpha 19 days after MGA). Neither breed nor
      PGF2alpha treatment effected (P > 0.05) 72 h estrous response, total-AI pregnancy
      rate, or CL regression rate. In conclusion, treating yearling BI heifers with
      split treatments of PGF2alpha (given on two consecutive days) improved estrous
      response and pregnancy rates by increasing PGF2alpha-induced luteolysis.

PMID- 15955359
TI  - The effect of gamete co-incubation time during in vitro fertilization with frozen
      thawed unsorted and sex-sorted ram spermatozoa on the development of in vitro
      matured adult and prepubertal ewe oocytes.
AB  - In vitro matured adult (Experiment 1) and prepubertal (Experiment 2) ewe oocytes
      were co-incubated with unsorted or sex-sorted frozen-thawed spermatozoa for 2 to
      3 h (short) or 18 to 20 h (long) to determine the effects of reducing the gamete
      co-incubation time during IVF on subsequent embryonic development in vitro. For
      oocytes derived from adult ewes, there were no differences in oocyte
      fertilization and cleavage at 24 h post insemination (hpi) between types of
      spermatozoa or co-incubation times (P > 0.05). By 48 hpi, oocyte cleavage was
      higher after a short (390/602, 64.8%) compared with a long (381/617, 61.7%) co
      incubation (P < 0.05), and was not significantly different for unsorted (266/372,
      71.5%) and sex-sorted (505/849, 59.9%) spermatozoa. Blastocyst formation from
      cleaved oocytes was similar for unsorted (150/266, 56.4%) and sex-sorted
      (295/505, 58.4%) spermatozoa, but was higher after a short (240/390, 61.5%) than
      long (205/381, 53.8%) co-incubation (P < 0.05). Oocyte development to the
      blastocyst stage was not different for unsorted (150/372; 40.3%) and sex-sorted
      (295/847; 34.8%) spermatozoa but was significantly increased by a short (240/602,
      39.9%) compared with a long (205/617, 33.2%) co-incubation. Fertilization of
      oocytes from prepubertal ewes was similar for types of spermatozoa and for
      duration of co-incubation. Oocyte cleavage (48 hpi) was similar for a short
      (241/377, 63.9%) and long (226/349, 64.8%) co-incubation with unsorted
      spermatozoa, but was increased (P < 0.05) by a long co-incubation (286/500, 57.2%
      versus 163/517, 31.5%) with sex-sorted spermatozoa. Blastocyst formation from
      cleaved oocytes was similar for unsorted (230/467, 49.3%) and sex-sorted
      (186/449, 41.4%) spermatozoa, and a short (200/404, 49.5%) or long (216/512,
      42.1%) co-incubation. However, oocyte development to the blastocyst stage was
      higher (P < 0.05) after IVF with unsorted (230/726, 37.1%) than sex-sorted
      (186/1017, 18.3%) spermatozoa. Reducing the duration of gamete co-incubation did
      not deleteriously affect the in vitro development of adult and prepubertal ewe
      derived oocytes after IVF with unsorted and sex-sorted spermatozoa. In general,
      sex-sorting had no substantial influence on fertilization and embryo development
      rates.

PMID- 15955360
TI  - Exogenous hyaluronic acid enhances porcine parthenogenetic embryo development in
      vitro possibly mediated by CD44.
AB  - Exogenous hyaluronic acid (HA) has been reported to improve early embryo
      development in vitro in pigs and cows. Although early embryo development in vitro
      is improved by exogenous HA, the mechanism mediating the action of HA is not
      clearly defined. In the present study, two possible HA actions on early embryo
      development were proposed to understand interactions between HA and the embryos
      using porcine parthenotes. We hypothesized that improvement of early embryo
      development mediated by HA would be caused by embryo-derived growth factors due
      to the high molecular weight of HA or cellular response through its receptor
      (CD44). We examined the effects of HA molecular weight on parthenogenetic embryo
      development, permeability of HA into the zona pellucida, expression of CD44 in
      porcine parthenotes at various stages, and blocking interactions between HA and
      CD44 by monoclonal anti-CD44 antibody (mCD44Ab). As a result, although
      development of porcine parthenotes to the blastocyst stage was significantly
      enhanced by exogenous HA with various molecular weights, there was no difference
      in blastocyst formation among the various molecular weights (P < 0.05).
      Immunofluorescence revealed that exogenous HA was accessible to CD44 through the
      zona pellucida, irrespective of the oocyte activation and that CD44 was also
      expressed in both oocytes and parthenotes at all developmental stages. In
      addition, development of parthenotes was partially blocked by mCD44Ab. In
      conclusion, we demonstrated that exogenous HA enhanced development of porcine
      parthenotes in vitro. This improvement mediated by exogenous HA on
      parthenogenetic embryo development was possibly caused by cellular response via
      CD44.

PMID- 15955361
TI  - The temporal relationship between patterns of LH and FSH secretion, and
      development of ovulatory-sized follicles during the mid- to late-luteal phase of
      sheep.
AB  - The aim of the present study was to investigate the temporal relationship between
      the secretory pattern of serum LH and FSH concentrations and waves of ovarian
      antral follicles during the luteal phase of the estrous cycle in sheep. The
      growth pattern of ovarian antral follicles and CL were monitored by transrectal
      ultrasonography and gonadotropin concentrations were measured in blood samples
      collected every 12 min for 6 h/d from 7 to 14 d after ovulation. There were two
      follicular waves (penultimate and final waves of the cycle) emerging and growing
      during the period of intensive blood sampling. Mean and basal LH concentrations
      and LH pulse frequency increased (P < 0.001) with decreasing progesterone
      concentration at the end of the cycle. Mean and basal FSH concentrations reached
      a peak (P < 0.01) on the day of follicular wave emergence before declining to a
      nadir by 2 d after emergence. None of the parameters of pulsatile LH secretion
      varied significantly with either the emergence of the final follicular wave or
      with the end of the growth phase of the largest follicle of the penultimate wave
      of the cycle. However, mean and basal LH concentrations did increase (P < 0.05)
      after the end of the growth phase of the largest follicle of the final follicular
      wave of the cycle. Furthermore, the end of the growth phase of the largest
      follicle of the final wave coincided with functional luteolysis. In summary,
      there was no abrupt or short-term change in pulsatile LH secretion in association
      with the emergence or growth of the largest follicle of a wave. We concluded that
      the emergence and growth of ovarian antral follicles in follicular waves do not
      require changes in LH secretion, but may involve changes in sensitivity of
      ovarian follicles to serum LH concentrations.

PMID- 15955362
TI  - Relationship between semen quality and pixel-intensity of testicular
      ultrasonograms after scrotal insulation in beef bulls.
AB  - The objective of this study was to determine the relationship between semen
      quality and testicular pixel-intensity derived from image analysis of
      ultrasonograms after scrotal insulation in bulls. In addition, the ability to
      predict semen quality based on testicular pixel-intensity was evaluated. Sixteen
      beef bulls were selected on the basis of satisfactory semen quality and normal
      testicular ultrasonogram appearance. Bulls were allocated into two groups for
      scrotal insulation for 4 days (group 1) or 8 days (group 2). Semen was collected
      and evaluated twice weekly and testicular ultrasonograms were evaluated once
      weekly for 8 weeks after removal of scrotal insulation. In general, the
      percentages of motile and morphologically normal spermatozoa decreased below pre
      insulation levels from 1 to 5 weeks after scrotal insulation removal. Overall,
      group 1 had greater (P < 0.01) percentages of motile and normal spermatozoa than
      group 2. Mean testicular pixel-intensity (PI), and the number of pixels
      corresponding to the intensity that occurs most frequently (NP) decreased in the
      first 2-3 weeks after scrotal insulation, coincidently with the decrease in sperm
      motility and normal morphology. When the entire data set was evaluated, there was
      no association between testicular PI or NP with semen quality observed at the
      same week of ultrasound examinations. However, regression models indicated that
      testicular PI and NP accounted for 13-25% of the variation in sperm motility and
      morphology in ejaculates collected 2-4 weeks after ultrasound exam. Testicular PI
      and NP had moderate sensitivity and negative predictive values (64.5-82.6%), but
      low specificity and positive predictive values (33.3-61.2%) as predictors of
      satisfactory semen quality (> or = 60% motile spermatozoa and > or = 70%
      morphologically normal spermatozoa) for ejaculates collected 2-4 weeks after
      ultrasound exam. In conclusion, the deleterious effects of scrotal insulation on
      semen quality were dependent on the length of the period of insulation and were
      associated with changes in testicular ultrasonogram pixel-intensity. Testicular
      ultrasonogram pixel-intensity had a better association with future semen quality
      than with present semen quality and was a better predictor of unsatisfactory
      semen quality than satisfactory semen quality.

PMID- 15955363
TI  - Activity, substrate detection and immunolocalization of glutathione peroxidase
      (GPx) in bovine reproductive organs and semen.
AB  - The purpose of the current study was to further investigate the role of the
      antioxidant selenium-dependent enzyme glutathione peroxidase (GPx) in
      reproductive organs and semen from bulls. To this end a fast and convenient
      combined method for immune detection and substrate localization was adapted,
      which allows the assessment of both molecular weight and peroxidase activity of
      proteins on one and the same SDS-PAGE gel plate. After routine semen analysis of
      ejaculates, a spectrophotometrical assay of GPx activity in bovine semen was
      performed. For the immunological analyses performed, a rabbit polyclonal
      monospecific antibody against GPx was raised. Substrate detection and
      immunolocalization of GPx in lysates from bovine testis, epididymis, spermatozoa,
      and seminal plasma was performed. In order to determine the localization of GPx
      in spermatozoa, immunofluorescence analysis was performed. A positive correlation
      was established between GPx activity in semen and the number of motile
      spermatozoa. A negative correlation was observed between GPx activity and the
      number of immotile spermatozoa. The combined method for immunodetection and
      substrate localization was tested and proved reliable. Both tetramer and monomer
      forms of GPx were detected in lysates from testis, epididymis, and spermatozoa.
      We found no GPx activity in seminal plasma. Immunofluorescence shows the presence
      of GPx chiefly in the mitochondrial and in the acrosome regions of spermatozoa.
      GPx activity remained stable under the extreme experimental conditions.

PMID- 15955364
TI  - Comparison of fertility and embryo mortality following artificial insemination of
      common duck females (Anas Platyrhynchos) with semen from common or Muscovy
      (Cairina Moschata) drakes.
AB  - The purpose of this study was to compare fertility and early embryo mortality
      rates (< or = 5 days of incubation) following artificial insemination (AI) of
      common duck females (Anas Platyrhynchos) with semen from either common or Muscovy
      (Cairina Moschata) drakes at various periods of the reproductive season (Period
      I, 27-35 weeks; Period II, 39-43 weeks and Period III, 49-56 weeks). Based on
      observations performed by stereomicroscopy on eggs laid from Days 2 to 10 after
      AI, we confirmed that fertility was significantly lower in the interbred compared
      to the purebred cross at each of the periods tested (purebred 58.1, 61.2 and 54.2
      versus crossbred 31.0, 40.4 and 39.5 at Periods I, II and II, respectively; 0.01
      < P < 0.001). In a complementary experiment, we demonstrated that the number of
      perivitelline spermatozoa (NPS) was markedly lower in mule (crossbred) eggs
      compared to common (purebred) eggs, a strong indication that initial sperm
      selection occurring in the lower oviduct is probably more intense after crossbred
      compared to purebred insemination. Comparison of early embryo mortality (EEM)
      between mule and common duck eggs indicated that increased levels of EEM in mule
      embryos corresponded to Stages II-IV of the Eyal-Giladi and Kochav classification
      (EGK). While a similar age-dependent increase in early embryo mortality was
      observed in eggs from both genetic origins during the latter periods of the
      reproductive season, it was also established that embryo mortality due to
      parental age was related rather to Stages X-XIV of the EGK classification in eggs
      from both genetic origins. It is concluded that the relative subfertility of mule
      compared to common duck eggs is probably the consequence of a more intense rate
      of selection of heterologous than homologous spermatozoa occurring in the vaginal
      portion of the oviduct while the causal origins of EEM in mule duck eggs can at
      least in part be identified on the basis of precise staging (by stereomicroscopy)
      of dead embryos.

PMID- 15955365
TI  - Evaluation of rapidly disintegrating tablets manufactured by phase transition of
      sugar alcohols.
AB  - The aim of the present study was to assess the properties of rapidly
      disintegrating (RD) tablets manufactured by the phase transition method. RD
      tablets were produced by compressing powder containing erythritol (melting point:
      122 degrees C) and xylitol (melting point: 93 approximately 95 degrees C), and
      then heating at about 93 degrees C for 15 min. The hardness and oral
      disintegration time of the heated tablets increased with an increase of the
      xylitol content. These results suggested that the heating process and xylitol
      content might influence the properties of RD tablets. Then we evaluated the
      physicochemical properties of the RD tablets, including the median pore size,
      crystallinity, hardness, and oral disintegration time of tablets made with and
      without heating. After heating, the median pore size of the tablets was increased
      and tablet hardness was also increased. The increase of tablet hardness with
      heating and storage did not depend on the crystal state of the lower melting
      point sugar alcohol. It is concluded that a combination of low and high melting
      point sugar alcohols, as well as a phase transition in the manufacturing process,
      are important for making RD tablets without any special apparatus.

PMID- 15955366
TI  - Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel-
      effect of additives.
AB  - Injectable polymeric formulation for paclitaxel was studied. Poly ricinoleic acid
      and sebacic acid were synthesized. The effect of additives on the viscosity of
      polymer, paclitaxel release, and polymer degradation was investigated both in
      vitro and in vivo. Additives that were used in this study were ricinoleic acid,
      phospholipid, PEG 400, and PEG 2000. Addition of 20% ricinoleic acid to
      P(SA:RA)3:7 liquefied the formulation and allowed injection of the formulation
      containing paclitaxel via a 22-G needle at room temperature with no effect on
      paclitaxel release rate. Addition of PEG 400, PEG 2000, and phospholipid to the
      formulation did not affect the paclitaxel release from the formulation. The
      degradation of modified formulations with paclitaxel and additives was examined
      in vitro and by subcutaneous injection of liquid formulations to the backspace
      via a 22-G needle into seven groups of four C3H mice. In vivo formulations with
      additives (20% ricinoleic acid and PEG or phospholipid) and 5% paclitaxel content
      degraded faster than the formulation with only 20% ricinoleic acid and the same
      paclitaxel content: 51% and 54% versus 43%. The slowest degradation (26% in 1
      week) was of the formulation containing 10% paclitaxel. The release rate in vivo
      was affected by the paclitaxel content; the higher the content, the slower was
      the release. By using additives, we could adjust the physical characteristics of
      the surgical paste while maintaining a desirable system for sustained paclitaxel
      release.

PMID- 15955367
TI  - Role of zinc in formulation of PLGA/PLA nanoparticles encapsulating betamethasone
      phosphate and its release profile.
AB  - The purpose of this study was to develop poly(D,L-lactic/glycolic acid) (PLGA) or
      poly(D,L-lactic acid) (PLA) nanoparticles of less than 200 nm in diameter that
      encapsulated water-soluble corticosteroid derivatives for sustained release and
      targeting to inflammatory sites. Nanoparticles were prepared with PLGA (or PLA),
      zinc, betamethasone phosphate and surfactant by an oil-in-water solvent diffusion
      method. With this method, the efficiency of encapsulating betamethasone phosphate
      in the nanoparticles and the particle size were significantly affected by various
      factors, such as the concentration of PLGA (or PLA) and the amount of zinc added.
      Nanoparticles ranging from 80 to 250 nm in diameter could be prepared, with a
      maximum betamethasone phosphate content of 8% (w/w). Betamethasone phosphate was
      gradually released from the nanoparticles in diluted serum, and the release rate
      depended on the glycolic/lactic acid ratio and on the molecular weight of PLGA or
      PLA. Betamethasone was gradually released over at least 8 days from murine
      macrophages that had internalized betamethasone phosphate-encapsulated
      nanoparticles in vitro, and the rate of release was slower than from
      nanoparticles prepared without zinc. These results suggest that zinc increases
      the efficiency of encapsulating betamethasone phosphate in nanoparticles and also
      promotes sustained release of betamethasone phosphate from the nanoparticles.

PMID- 15955369
TI  - Genetics of type 2 diabetes mellitus.
AB  - The clinical picture of type 2 diabetes mellitus (T2DM) is formed by impairment
      in insulin secretion and resistance to insulin action. As a result of intensive
      efforts of the scientists around the world mutations and polymorphisms in a
      number of genes were linked with monogenic and polygenic forms of T2DM. Two major
      strategies were used in this research: genome scanning and the candidate gene
      approach. Monogenic forms, despite their rarity, constitute a field where
      substantial progress has been made in the dissection of the molecular background
      of T2DM. Monogenic forms of T2DM with profound defect in insulin secretion
      include subtypes of maturity onset diabetes of the young (MODY), maternally
      inherited diabetes with deafness (MIDD) caused by mitochondrial mutations, and
      rare cases resulting from insulin gene mutations. The majority of proteins
      associated with MODY are transcription factors, such as hepatocyte nuclear factor
      4alpha (HNF-4alpha), HNF-1alpha, insulin promoter factor-1 (IPF-1), HNF-1beta,
      and NEUROD1. They influence expression of the other genes through regulation of
      mRNA synthesis. Only MODY2 form is associated with glucokinase, a key regulatory
      enzyme of the beta cell. There are striking differences in the clinical picture
      of MODY associated with glucokinase and MODY associated with transcription
      factors. Three monogenic forms of T2DM characterized by severe insulin resistance
      are the consequence of mutations in the PPARgamma, ATK2, and insulin receptor
      genes. Patients with monogenic T2DM, particularly with MODY, sometimes, develop
      discrete extra-pancreatic phenotypes; for example, lipid abnormalities or a
      variety of cystic renal diseases. Efforts aiming to identify genes responsible
      for more common, polygenic forms of T2DM were less effective. These forms of T2DM
      have a middle/late age of onset and occur with both impaired insulin secretion
      and insulin resistance. Their clinical picture is created by the interaction of
      environmental and genetic factors, such as frequent polymorphisms of many genes,
      not just of one. These polymorphisms may be localized in the coding or regulatory
      parts of the genes and are present, although with different frequencies, in T2DM
      patients as well as in healthy populations. Sequence differences in a few genes
      have been associated, so far, with complex, polygenic forms of T2DM, for example,
      calpain 10, PPARgamma, KCJN11, and insulin. In addition, some evidence exists
      that genes, such as adiponectin, IRS-1, and some others may also influence the
      susceptibility to T2DM. It is expected that in the nearest future more T2DM
      susceptibility genes will be identified.

PMID- 15955370
TI  - Metabolic syndrome in relationship to type 2 diabetes and atherosclerosis.
AB  - Metabolic syndrome affects approximately one quarter of population in developed
      countries. Its presence is a major risk for development of both type 2 diabetes
      (T2DM) and atherosclerosis. The prevalence of cardiovascular disease is 2-3 times
      higher in individuals with metabolic syndrome than in age-matched controls. Most
      important components of metabolic syndrome are insulin resistance with or without
      glucose intolerance, abdominal obesity, atherogenic dyslipidaemia, hypertension,
      prothrombotic state and proinflammatory state. Early identification of subjects
      with metabolic syndrome is very important, since they represent a target group
      for multiple lifestyle and pharmacological interventions. Lifestyle
      interventions, antiobesity drugs and drugs increasing insulin sensitivity
      prevented development of T2DM in subjects with impaired glucose tolerance in
      randomized trials. Treatment of atherogenic dyslipidaemia to the therapeutic
      goals defined for diabetic patients seems reasonable and both statins and
      fibrates could be used based on evidence from clinical trials. Treatment of
      hypertension should also aim for target levels similar to those in diabetic
      patients. Using drugs affecting renin-angiotensin II axis, as first choice seems
      reasonable based on evidence from clinical trials showing the ability of these
      drugs to prevent T2DM and decrease albuminuria.

PMID- 15955371
TI  - Pathophysiology of type 2 diabetes: rationale for different oral antidiabetic
      treatment strategies.
AB  - Type 2 diabetes mellitus is a chronic metabolic disorder that results from
      defects in both insulin secretion and insulin action. Both insulin resistance and
      beta-cell failure are genetically determined to some extent; however,
      environmental factors contribute to exacerbate both abnormalities. Type 2
      diabetic individuals are also characterised by reduced beta-cell mass likely due
      to increased cellular apoptosis. The early use of insulin therapy in type 2
      diabetes may prove beneficial to prevent further beta-cell loss and need for
      exogenous insulin. Treatment options with oral agents are quite diverse,
      including insulin sensitizers, alpha-glucosidase inhibitors, and beta-cell
      secretagogues. Although in recent years the emphasis on initial therapy has been
      shifting from insulin secretagogues to insulin sensitizers such as metformin and
      thiazolidinediones, questions remain as to genetic and/or phenotypic factors may
      dictate a different choice of the first antidiabetic drug to be used. It is not
      totally clear whether monotherapy should be pursued until the maximally effective
      dose of a given drug or combination therapy should be used to target distinct
      pathogenic defects in a single patient. Individual phenotypic and genetic
      characterisation of the patients may help to solve this conundrum, eventually
      providing tailored treatment algorithms.

PMID- 15955372
TI  - Early use of insulin in type 2 diabetes.
AB  - Type 2 diabetes is a disease characterised by peripheral insulin resistance, as
      well as by pancreatic beta cell dysfunction. This process is in part due to
      elevated blood glucose and free fatty acids--termed glucolipotoxicity. The
      traditional pathway of treating type 2 diabetes in a stepwise manner, beginning
      with life style modifications and continuing with oral hypoglycaemic agents leads
      to a protracted period of unnecessary hyperglycaemia. A new approach, targeted at
      alleviating the deleterious effects of hyperglycaemia and elevated free fatty
      acids by acutely lowering both with intensive insulin therapy, has yielded
      prolonged remissions in therapy in which only diet was necessary to maintain
      normoglycaemia. This new approach, its rationale, benefits and misgivings are
      discussed in this review.

PMID- 15955373
TI  - Prevention and treatment of diabetic nephropathy.
AB  - Increasing number of diabetic patients develop different stages of renal failure.
      However, often an inappropriate parameter, the serum creatinine is measured as a
      marker of glomerular function. Calculated glomerular filtration rate or
      endogenous creatinine clearance are suggested to be used for the estimation of
      the glomerular function. Important structures preventing proteinuria in the
      kidney are glomerular basement membrane, podocytes and proximal tubular cells. In
      diabetes mellitus loss of nephrin of podocytes can play a role in the development
      of microalbuminuria, and podocyte desquamation may result in the progression to
      proteinuria. In diabetes mellitus there is an increased formation of advanced
      glycation endproducts (AGE), of which the only elimination organ is the kidney.
      The AGE induce proteinuria and atherosclerosis. Therefore, in diabetes mellitus a
      vicious circle develops due to proteinuria, nephron loss and accumulation of AGE,
      which play a role in the initiation and progression of diabetic nephropathy and
      atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin
      receptor blockers having antiproteinuric effect may decrease the risk of diabetic
      nephropathy and atherosclerosis. Improvement of carbohydrate metabolism with a
      consequential decrease in the formation of AGE is an important contributor to the
      prevention and treatment of diabetic nephropathy and atherosclerosis.

PMID- 15955374
TI  - Learning from large cardiovascular clinical trials: classical cardiovascular risk
      factors.
AB  - The number of cardiovascular risk factors significantly influences age adjusted
      cardiovascular death rates according to the data of the MRFIT Trial. Up to 60% of
      patients with Type 2 diabetes have concomitant hypertension. In the HOT
      (Hypertension Optimal Treatment) Study lowering of blood pressure was
      particularly beneficial in the subgroup of diabetes mellitus: there was a 51%
      reduction in major cardiovascular events in target group<or=80 mmHg, compared
      with target group<or=90 mmHg (p=0.005). Analysis of the diabetic patient group in
      the CAPPP (The CAPtopril Prevention Project) showed that captopril was superior
      for preventing cardiovascular events in hypertensive patients with diabetes. In
      the diabetic cohort of the LIFE Study losartan was more effective than athenolol
      in reducing cardiovascular morbidity and mortality as well as mortality from all
      causes in patients with hypertension, diabetes and left ventricular hypertrophy.
      In the Heart Protection Study 5963 people with diabetes were studied. For the
      first occurrence of any major vascular events among diabetic participants, there
      was a 22% reduction in the event rate simvastatin-allocated versus placebo
      allocated patients (p<0.0001). DAIS (Diabetes Atherosclerosis Intervention Study)
      data suggest that treatment with fenofibrate reduces the angiographic progression
      of coronary artery disease in patients with Type 2 diabetes. According to results
      on multifactorial intervention in patients with Type 2 diabetes (the STENO-2
      study) the overall cardiovascular risk reduction was 53%. In conclusion,
      management of cardiovascular risk factors should be considered as the cornerstone
      of diabetes care.

PMID- 15955375
TI  - Can the atherosclerosis prevention targets be achieved in type 2 diabetes?
AB  - Type 2 diabetes mellitus is beside hyperglycemia frequently accompanied by
      dyslipidemia, arterial hypertension, obesity and other atherosclerosis risks. The
      article summarizes current status demonstrating that we are far from recommended
      targets, especially with diabetes, blood pressure and lipid controls. More
      aggressive drug treatment together with life style changes will be necessary to
      reach our goals in Type 2 diabetic patients.

PMID- 15955377
TI  - Influence of insulin treatment on insulin sensitivity in insulin requiring type 2
      diabetes patients.
AB  - Insulin resistance in type 2 diabetes subjects was investigated before and 6
      months after insulin administration in 43 type 2 diabetes patients (28 females
      and 15 males). Their age was 56.1+/-8.6 years, diabetes duration 11.7+/-6.8
      years, BMI 29.5+/-5.3 kg/m2. All patients were on maximal dosage of oral
      hypoglycaemic agents and had poor metabolic control (HbA1c 11.2+/-1.6%). Insulin
      sensitivity was measured by euglycaemic clamp (insulin infusion rate 1 mU kg-1
      min-1). The glucose disposal rate (M-value) was considerably lower in patients
      (2.4+/-1.6 mg kg-1 min-1, 0.2-8.1) compared with healthy subjects (7.1+/-0.2 mg
      kg-1 min-1, p<0.01). M-value was strongly associated with WHR (r=-0.41, p<0.05).
      The patients with poorest insulin sensitivity had the highest level of total
      cholesterol (r=-0.41, p=0.02) and LDL-cholesterol (r=-0.38, p=0.03). After 6
      months of insulin treatment BMI was 30.3+/-4.2 kg/m2 (p<0.05), mean weight
      increase was 2.7+/-0.8 kg. M-value was substantially increased to 4.5+/-2.3 mg kg
      1 min-1 (p<0.001), the degree of improvement depended on basal insulin
      sensitivity (r=-0.55, p<0.01). HbA1c was reduced to 7.7+/-1.4% (p<0.01), the
      correlation M-value with change of HbA1c (r=-0.59, p<0.01) was shown. Total
      cholesterol decreased from 6.3+/-1.1 to 5.4+/-1.1 mmol/l, LDL-cholesterol from
      4.1+/-1.1 to 3.4+/-1.0 mmol/l, triglycerides from 2.6+/-1.6 to 1.6+/-0.7 mmol/l
      (p<0.001). In conclusion, insulin treatment of type 2 diabetes patients leads to
      decrease in insulin resistance due to reduction in glucose toxicity and plasma
      atherogenicity despite weight gain.

PMID- 15955378
TI  - Correlation of serum ghrelin levels with body mass index and carbohydrate
      metabolism in patients treated with atypical antipsychotics.
AB  - The prevalence of diabetes mellitus and metabolic syndrome is higher in patients
      with schizophrenia than in the normal population. Atypical antipsychotic drugs
      are used in psychiatry since the beginning of 1990. These drugs differ from the
      "typical" antipsychotics used previously, as they have less extrapyramidal side
      effects, and because of this they are tolerated better, but are associated with
      weight-gain and disturbances in carbohydrate metabolism. Ghrelin is an orexigen
      hormone partaking in body weight regulation. It is produced in the
      enteroendocrine P/D1 cells of the gastric mucosa and secreted to the circulation.
      The aim of our study was to determine ghrelin levels of atypical antipsychotic
      treated patients in relationship with their body mass index (BMI) and
      carbohydrate metabolism. We measured the fasting serum ghrelin levels in 56
      patients (male/female: 16/40, age mean+/-S.D.: 50.6+/-5.6 years) treated with
      atypical antipsychotics (clozapine, olanzapine, risperidon and quetiapine), and
      in 75 healthy control subjects, age and gender matched (RIA Linco, USA) in
      relationship with their BMI and their fasting and 75 g OGTT 120 min blood glucose
      values. The serum ghrelin levels of the patient group were notably higher (1333+/
      659 pg/ml) than in the control group (368+/-103, p<0.0001; Mann-Whitney). We
      found no difference among the four antipsychotics in weight-gain, diabetes
      prevalence and the serum ghrelin levels. The BMI of the patient group was
      significantly higher (29.3+/-7.2 kg/m2 versus 24.3+/-3.7 kg/m2, p<0.0001; Mann
      Whitney); 32% of them had blood glucose abnormality (18/56). There was no
      difference between the ghrelin levels in diabetic and non-diabetic patients. We
      found a significant negative linear correlation between the serum ghrelin and BMI
      (r=-0.35, p=0.0078; Spearman), the ghrelin and fasting blood glucose (r=-0.32,
      p=0.015) and OGTT 75 g 120 min blood glucose levels (r=-0.27, p=0.036). The
      orexigen effect of elevated serum ghrelin levels can contribute to the weight
      gain and high diabetes prevalence associated with atypical antipsychotic
      treatment. The link between atypical antipsychotic treatment and elevated serum
      ghrelin levels is unknown so far, but a dysregulation of the central feedback
      mechanism can be hypothesised.

PMID- 15955379
TI  - Role of endothelial dysfunction in the development of cardiorenal syndrome in
      patients with type 1 diabetes mellitus.
AB  - We examined the role of endothelial dysfunction in the development and
      progression of cardiorenal syndrome in 93 patients with type 1 diabetes mellitus.
      PATIENTS: According to the stage of renal insufficiency all patients were divided
      into equal groups: those with normal albumin excretion rate, with
      microalbuminuria, with proteinuria, and with chronic renal failure. We analyzed
      endothelial flow-mediated dilation of the brachial artery, levels of endothelin
      1, von Willerbrand factor, C-reactive protein, renal:albumin and protein
      excretion rates, glomerular filtration rate (GFR), and cardiovascular (ECG,
      echocardiography, blood pressure monitoring) functions. RESULTS: There were
      negative correlations between the GFR, BP level and endothelial dysfunction
      markers. At the same time GFR correlated positively with the coefficient of
      sensitivity of endothelium to shear stress. There were also positive correlations
      between BP, permeability of glomerular filter and endothelial dysfunction markers
      and negative correlation with the coefficient of sensitivity of endothelium to
      shear stress and GFR. Left ventricle mass correlated with markers of endothelial
      dysfunction and stage of renal disease. Patients with chronic renal failure had
      negative correlations between LVM and GFR, ILVM and GFR and a positive
      correlation between ejection fraction and GFR. CONCLUSIONS: There is a close
      relationship between endothelial dysfunction and development and progression of
      renal and cardiovascular pathology in patients with type 1 diabetes mellitus.

PMID- 15955380
TI  - Can type 2 diabetes mellitus be considered preventable?
AB  - The primary prevention of type 2 diabetes mellitus (T2DM) is of great importance.
      There is now substantial evidence that T2DM can be prevented or delayed by
      lifestyle modification. A statistically significant reduction of relative risk of
      newly diagnosed T2DM was observed in large clinical trials with metformin,
      acarbose or orlistat in subjects with impaired glucose tolerance as well as with
      troglitazone in women with previous gestational diabetes. A relative risk
      reduction of newly diagnosed diabetes was observed in prospective, double blind
      clinical studies evaluating the effect of different antihypertensive drugs (ACE
      inhibitors, angiotensin repector blockers, calcium channel blockers) or that of
      lipid-lowering agents (pravastatin) on the cardiovascular morbidity and mortality
      in high risk patients. In studies with postmenopausal hormone replacement therapy
      a relative risk reduction of newly developed T2DM was also observed. Thus, T2DM
      should be considered as a preventable disease. Nevertheless, it is noteworthy
      that oral antidiabetic drugs with an indication of preventing T2DM are not
      registered in several countries at present, so that drug therapy should not be
      used as a routine for preventing diabetes. On the other hand, patients with pre
      diabetes (impaired fasting glycaemia, impaired glucose tolerance) should be given
      counseling on weight loss as well as instruction for increasing physical activity
      in order to prevent T2DM.

PMID- 15955381
TI  - Possible novel index determined by the glucose clamp test for selection of a
      suitable therapy for each type 2 diabetic patient.
AB  - The hallmark of type 2 diabetes is insulin resistance and insufficient insulin
      secretion, and appropriate therapy should be selected for each patient. In this
      study, to establish some index to select suitable therapy for each patient, we
      evaluated insulin sensitivity and insulin secretion with euglycemic
      hyperinsulinemic clamp and hyperglycemic clamp tests, respectively, and found
      that specific GIR index (GIRxIRI (90)) could be a useful marker to select
      suitable therapy for each type 2 diabetic patient (GIR: glucose infusion rate in
      euglycemic hyperinsulinemic clamp test; IRI (90): plasma insulin level 90 min
      after starting the hyperglycemic clamp test).

PMID- 15955382
TI  - A comparison of the effects of pioglitazone and rosiglitazone combined with
      glimepiride on prothrombotic state in type 2 diabetic patients with the metabolic
      syndrome.
AB  - OBJECTIVE: To compare the effects of glimepiride plus pioglitazone or plus
      rosiglitazone in diabetic patients with the metabolic syndrome on coagulation and
      fibrinolysis parameters. STUDY DESIGN AND METHODS: 91 type 2 diabetic patients
      with the metabolic syndrome participated. All patients took a fixed dose of
      glimepiride, 4 mg/day. We administered pioglitazone (15 mg/day) or rosiglitazone
      (4 mg/day) in a randomized, controlled, double-blind clinical study. We compared
      body mass index (BMI), glycemic control, coagulation and fibrinolysis parameters,
      and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 87
      completed the study (pioglitazone n=45 or rosiglitazone n=42). Body mass index
      increased after 12 months compared to baseline (p<0.05) in both groups. A
      significant decrease in glycated haemoglobin (HbA(1c)) was observed after 9
      (p<0.05), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean
      fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were
      lower in both groups (p<0.05 and 0.01, respectively), as were fasting plasma
      insulin (FPI) and postprandial plasma insulin (PPI) (p<0.05 and p<0.01,
      respectively). An improvement in the homeostasis model assessment index (HOMA
      index) was seen at 9 and 12 months (p<0.05 and 0.01, respectively) compared to
      the baseline value in both groups. Plasminogen activator inhibitor 1 (PAI-1) was
      significant lower (p<0.05) in both groups after 12 months compared to the
      baseline values. No changes in tissue-plasminogen activator (t-PA) and fibrinogen
      (Fg) were seen during the study nor were there any changes in transaminases.
      CONCLUSIONS: We conclude that the addition of a thiazolinedione to glimepiride
      treatment in type 2 diabetic subjects with the metabolic syndrome is associated
      with a slight but significant reduction of PAI-1 value, related to a similar
      reduction in insulinresistance.

PMID- 15955383
TI  - Characteristics of basal insulin requirements by age and gender in Type-1
      diabetes patients using insulin pump therapy.
AB  - Establishment of appropriate basal insulin levels is an essential component of
      intensive insulin therapy. While the existence of a "dawn phenomenon" is widely
      recognized, the present study sought to establish whether diurnal basal insulin
      patterns exist in Type-1 diabetes, and whether these patterns vary by age and
      gender. Participant data was drawn from 322 Type-1 insulin pump users treated at
      a private diabetes education practice in suburban Philadelphia. All participants
      completed a battery of fasting tests designed to match basal insulin levels to
      endogenous glucose production and insulin sensitivity. Analysis of resultant
      basal patterns revealed significant differences between juvenile (age < or =20)
      and adult (age >20) basal insulin patterns. The younger group exhibited a more
      pronounced and sustained night-time peak; the older group exhibiting a briefer
      and less pronounced early-morning peak. Lower overall basal insulin requirements
      were found in the youngest (age < or =10) and oldest (age >60) groups. No
      noteworthy gender differences were found. Results can serve as a guide for
      clinicians when initiating and fine-tuning patients who utilize basal/bolus
      insulin therapy.

PMID- 15955384
TI  - Characteristics of childhood and adult-onset type 1 diabetes in a multi-ethnic
      population.
AB  - OBJECTIVE: To compare patients with classic type 1 diabetes (T1D) diagnosed in
      childhood and adulthood regarding clinical presentation, GADA and HLA DR B1*03/04
      prevalence in a multi-ethnic population. METHODS: We studied 83 Brazilian
      patients with classic T1D divided in 2 groups: (1) diagnosed before 20 years old
      (n=42); (2) diagnosed at age 20 and up (n=41). All were interviewed and blood was
      sampled for GADA measurement and HLA DR B1 typing. RESULTS: The study population
      comprised 52 women and 31 men, 52 white and 31 non-white individuals with mean
      age of 29.94 (+/-10.95) years and mean disease duration of 10.37 (+/-7.37) years.
      The mean age at onset in groups 1 and 2 were, respectively, 11.48 and 27.2 years
      old. There were no significant differences between groups regarding diabetic
      ketoacidosis at presentation. A longer symptomatic period preceding the diagnosis
      was observed in group 2 (p=0.039). The prevalence of GADA and HLA DR B1*03/04 was
      similar between groups. HLA DR B1*13 was significantly more common in the group 1
      (p=0.024). GADA was more prevalent among patients with HLA DR B1*03 (p=0.02).
      CONCLUSION: In this study, T1D diagnosed in adulthood was associated with longer
      symptomatic period preceding diagnosis and lower prevalence of HLA DR B1*13, but
      there were no differences regarding ketoacidosis as a form of disease
      presentation, GADA (+) or HLA DR B1* 03/04.

PMID- 15955385
TI  - Relationship of obesity and visceral adiposity with serum concentrations of CRP,
      TNF-alpha and IL-6.
AB  - OBJECTIVE: To investigate the relationship between serum concentrations of the
      cytokines C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, and
      interleukin (IL)-6, and obesity and visceral adiposity. METHODS: A cross
      sectional study of 100 Korean adults free from pre-existing inflammatory disease
      or cancer was performed. Body mass index (BMI), waist circumference, and serum
      concentrations of CRP, TNF-alpha and IL-6 were measured. In 46 obese subjects,
      fat mass was assessed by bioimpedance analysis and abdominal fat distribution was
      determined by computerized tomography scan. RESULTS: Overall, serum
      concentrations of CRP, TNF-alpha and IL-6 were significantly correlated with
      weight, BMI, waist circumference, hip circumference, and waist-hip ratio. In
      obese subjects, CRP and IL-6 were significantly correlated with BMI, waist
      circumference and visceral adipose tissue. Multiple regression analysis showed
      that CRP was significantly associated with BMI, whereas IL-6 was significantly
      related with visceral adiposity in obese subjects. CONCLUSIONS: The positive
      associations of obesity and visceral adiposity with elevated cytokine levels
      suggest the importance of reducing obesity and visceral adiposity to prevent
      elevations in cytokine levels.

PMID- 15955386
TI  - Metabolic response to oral lipid overload in diabetes and impaired glucose
      tolerance.
AB  - Post-prandial hyperglycemia and hypertriglyceridemia have been related to
      atherogenesis. The aim of this study was to evaluate the response of plasma
      lipoproteins to a lipid overload in subjects with diabetes (DM), impaired glucose
      tolerance (IGT) and normals (N). Seventy-seven subjects were selected, 36-85
      years, plasma glucose (G)<140 mg/dl and triglycerides (TG)<150 mg/dl; those
      without diabetes underwent a glucose tolerance test (GTT), which classified them
      into three groups: N, 2h G<140 mg/dl, n=37; IGT, 2h G 140-200mg/dl, n=20; and DM,
      previous diabetes or 2h G>200mg/dl, n=20. They were submitted to a clinical
      evaluation and an oral lipid overload (1000 kcal, 58% fat). Fasting, 4 and 6-h
      blood samples after the meal were collected for G, insulinaemia (I), TG,
      cholesterol and their fractions, and HOMA-IR. Fasting and post-lipid overload
      lipoproteins were similar between groups, but 6h TG was still high in DM versus
      IGT and N as compared to their 4h values. There was a positive correlation
      between fasting TG versus 6h TG (r=0.78, p<0.001). We conclude that individuals
      with impaired glucose tolerance and with diabetes mellitus have a slower plasma
      reduction of triglycerides after lipid overload, as well as an altered glucose
      and post-prandial insulin response.

PMID- 15955387
TI  - Predictive values of anthropometric measurements for multiple metabolic disorders
      in Asian populations.
AB  - OBJECTIVE: Asians have a unique feature characterized by a low frequency of
      obesity, but a high frequency of diabetes and metabolic syndrome. It is important
      to develop simple and reliable anthropometric measurement tools for multiple
      metabolic disorders, but the cut-off values of anthropometric measurements for
      Asians have been less clear than those for Caucasians. RESEARCH DESIGN: Data from
      361 Japanese and 252 Mongolians aged 30-60 years were investigated for the
      relationship between multiple metabolic disorders parameters and anthropometric
      measurements. Pearson's correlation coefficients and receiver operating
      characteristic (ROC) analysis were done. RESULTS: Mongolians of both genders had
      significantly higher values for all anthropometric measurements than did the
      Japanese. The Japanese anthropometric measurements showed the highest correlation
      coefficient of the area under the curve (AUC) from an ROC analysis for HDL-C and
      triglyceride, while the Mongolians showed the highest values for HOMA-IR. BMI and
      waist circumference (WC) for both ethnic groups showed relatively higher AUCs for
      the multiple metabolic disorders parameters. Optimal cut-off values predicting
      multiple metabolic disorders in the Japanese were estimated at 24 BMI and 82 cm
      WC (men) and 23 BMI and 73 cm WC (women); for the Mongolian, 27 BMI and 92 cm WC
      (men) and 27 BMI and 84 cm WC (women). CONCLUSIONS: There were great differences
      in diagnostic accuracy for the anthropometric measurements by ethnicity, and a
      relatively lower magnitude of differences by kind of anthropometric measurement.
      The present study suggests that BMI and WC were useful for predicting multiple
      metabolic disorders in non-diabetic Mongolians and Japanese, while the use of
      plasma triglyceride and HDL-cholesterol levels in combination with BMI and WC may
      enhance the ability of predicting metabolic parameters in the Japanese.

PMID- 15955388
TI  - Prevalence and risk factors associated with the metabolic syndrome and
      dyslipidemia in White, Black, Amerindian and Mixed Hispanics in Zulia State,
      Venezuela.
AB  - Studies have highlighted the association between insulin resistance (IR) and
      several cardiovascular (CV) risk factors, including hypertension (HTN), obesity,
      dyslipidemia (i.e. high triglyceride and low HDL-cholesterol) and glucose
      intolerance, in a cluster known as the metabolic syndrome (MS). There are few
      data on the frequency of the MS and dyslipidemia in developing countries, and
      none in South America. To estimate the prevalence of the MS and its components in
      Zulia State, Venezuela, and to establish associated demographic and clinical
      factors, we evaluated 3108 Hispanic men and women aged 20 years or older from a
      cross-sectional survey of a random representative sample from each health
      district in Zulia State, Venezuela (1999-2001). Prevalence of the MS and
      dyslipidemia was defined according to the National Cholesterol Education Program
      (NCEP)/Adult Treatment Panel III (ATP III) criteria. The age-adjusted prevalence
      of MS and dyslipidemia was 31.2% and 24.1%, respectively, with higher rates in
      men than in women. Prevalence rates increased with age and with the degree of
      obesity. MS prevalence was lower in Amerindian (17.%) compared to Black (27.2%),
      White (33.3%) and Mixed (37.4%) men, but no differences were found among women.
      Overall, low HDL-cholesterol (65.3%), abdominal obesity (42.9%) and HTN (38.1%)
      were the most frequent MS components. After adjusting for age, sex and race
      groups, family history of diabetes, obesity and HTN were associated with the MS.
      Sedentary lifestyle also increased the risk of MS, event after adjusting for the
      same covariates, obesity and the degree of IR. These results suggest that MS is
      found in approximately one-third of the Venezuelan adult population in Zulia
      State, with higher prevalence in men related to the presence of dyslipidemia.
      Lifestyle interventions in MS subjects are needed in Venezuela to halt the burden
      of CV disease and diabetes.

PMID- 15955389
TI  - Treatment regimen determines the relationship between depression and glycemic
      control.
AB  - Several recent studies have suggested that depression is related to poorer
      glycemic control in patients with type 1 diabetes, but not in type 2 diabetes. We
      hypothesize that complexity of self-care regimen rather than the type of
      diabetes, is more important in determining this relationship of depression to
      glycemic control. METHODS: One thousand thirty-four adults with diabetes were
      recruited for the study. These patients were treated with: diet and exercise,
      oral medications, oral medications and insulin, 1-2 daily injections of insulin,
      and > or =3 daily injections. All participants completed the Beck depression
      inventory (BDI) and had a hemoglobin A(1c) (HbA(1c)) performed as part of routine
      clinical care. RESULTS: Pearson correlations between BDI scores and HbA(1c) were
      low and insignificant in all groups (0.015< or =r< or =0.066) except for those
      administering three or more daily shots of insulin (r=0.284; p=0.034).
      DISCUSSION: The results of this study clearly show that while depressive symptoms
      are significantly correlated to glycemic control in patients taking three or more
      insulin injections per day, there is no relationship in patients who are taking
      fewer than three injections per day.

PMID- 15955390
TI  - Ten-year mortality and glucose tolerance status in an elderly Finnish population.
AB  - The aim of this study was to determine the 10-year mortality rate of an elderly
      population aged 70 years or over (n=379) with reference to glucose tolerance
      status, taking into account other determinants of excess mortality. The baseline
      examination during 1991-1992 included a postal questionnaire, a physical
      examination and a 2h OGTT, which was classified according to both the 1985 WHO
      criteria and the 1999 WHO criteria. Follow-up was continued until death or until
      31 December 2001. 66% of men and 51% of women died within 10 years. In men, the
      cumulative mortalities were 84% for previously diagnosed diabetes, 67% for
      undiagnosed diabetes, 67% for impaired glucose tolerance (IGT) and 60% for normal
      glucose tolerance (NGT). The corresponding percentages for women were 76, 52, 49,
      and 40%. Male gender, poor self-rated health and previously diagnosed diabetes
      were the most powerful predictors of mortality. When adjustments were made for
      age, gender, BMI, cardiovascular disease, hypertension, physical exercise and
      self-rated health, the estimated relative mortality rate was 2.0 (95% CI 1.5-2.7)
      among previously diagnosed diabetic subjects, 1.3 (CI 0.8-2.2) among undiagnosed
      diabetic subjects and 1.1 (0.8-1.5) among IGT subjects compared to NGT subjects.
      These relative mortalities were higher in women than in men. When abnormal
      glucose tolerance was pooled into one category, the OR for excess mortality was
      1.4 (95% CI 1.1-1.9).

PMID- 15955391
TI  - Association between fasting glucose and C-reactive protein in a Japanese
      population: the Minoh study.
AB  - To investigate the association between fasting glucose and C-reactive protein
      (CRP), we examined 1715 Japanese individuals (723 men and 992 women) aged 40-69
      years who did not have medication for hypertension, diabetes, or dyslipidemia, a
      history of cardiovascular disease or CRP levels>10mg/l. There was a statistically
      significant unadjusted correlation between CRP and each component of the
      metabolic syndrome, including fasting glucose, fasting insulin, body mass index,
      systolic blood pressure, diastolic blood pressure, high-density lipoprotein
      cholesterol (negative), and triglycerides in both men and women. With adjustment
      for age, cigarette smoking, alcohol intake, and other components of the metabolic
      syndrome, the CRP increments (as back-transformed) compared with the lowest
      tertile of normal fasting glucose were 0.99, 1.05, 1.21, and 1.34mg/l (P for
      trend=0.008) with the second lowest and highest tertiles of normal fasting
      glucose, impaired fasting glucose, and type-2 diabetes, respectively in men. The
      respective adjusted CRP increments were 1.12, 1.23, 1.33, and 1.93mg/l (P for
      trend<0.001) in women. In the stratified analyses of CRP levels by sex, obesity
      status, and fasting glucose category or the number of components of the metabolic
      syndrome, an increase in CRP levels was greater in women than men with obesity
      and higher fasting glucose category (gender interaction: P<0.001) or an increased
      number of components of the metabolic syndrome (gender interaction: P=0.003).
      These results indicate that CRP levels increase continuously across the spectrum
      of fasting glucose in both sexes. This association is more pronounced in women.

PMID- 15955392
TI  - What do we (not) know about apoB, type 2 diabetes and obesity?

PMID- 15955393
TI  - A comparative analysis of drug safety withdrawals in the UK and the US (1971
      1992): implications for current regulatory thinking and policy.
AB  - By going beyond individual case studies and solely quantitative surveys, this
      paper systematically examines why there were over twice as many new prescription
      drugs withdrawn from the market on grounds of safety in the UK as there were in
      the US between 1971 and 1992. Drawing on interviews with regulators, industry
      scientists and others involved, and on regulatory data never before accessed
      outside governments and companies, five key hypotheses which might explain this
      difference in drug safety withdrawals are analysed. These are: (1) simply because
      the UK approved more new drugs than the US; (2) because of an industrial
      corporate strategy to seek approval of 'less safe' drugs in the UK earlier; (3)
      because British regulators were more vigilant at spotting post-marketing safety
      problems than their US counterparts; (4) because the slowness of the US in
      approving new drugs enabled regulators there to learn from, and avoid, safety
      problems that had already emerged in the UK or European market; and (5) because
      more stringent regulation in the US meant that they approved fewer unsafe drugs
      on to the market in the first place. It is concluded that the main explanation
      for fewer drug safety withdrawals in the US is that the regulatory agency there
      applied more stringent pre-market review and/or standards, which took longer than
      UK regulatory checks, but prevented unsafe drugs marketed in the UK from entering
      the US market. Contrary to the claims frequently made by the pharmaceutical
      industry and regulatory agencies on both sides of the Atlantic, these results
      imply that it is likely that acceleration of regulatory review times in the US
      and the UK since the early 1990s is compromising drug safety.

PMID- 15955394
TI  - Global trade, public health, and health services: stakeholders' constructions of
      the key issues.
AB  - Focusing mainly on the United States and Latin America, we aimed to identify the
      constructions of social reality held by the major stakeholders participating in
      policy debates about global trade, public health, and health services. In a multi
      method, qualitative design, we used three sources of data: research and archival
      literature, 1980-2004; interviews with key informants who represented major
      organizations participating in these debates, 2002-2004; and organizational
      reports, 1980-2004. We targeted several types of organizations: government
      agencies, international financial institutions (IFIs) and trade organizations,
      international health organizations, multinational corporations, and advocacy
      groups. Many governments in Latin America define health as a right and health
      services as a public good. Thus, the government bears responsibility for that
      right. In contrast, the US government's philosophy of free trade and promoting a
      market economy assumes that by expanding the private sector, improved economic
      conditions will improve overall health with a minimum government provision of
      health care. US government agencies also view promotion of global health as a
      means to serve US interests. IFIs have emphasized reforms that include reduction
      and privatization of public sector services. International health organizations
      have tended to adopt the policy perspectives of IFIs and trade organizations.
      Advocacy groups have emphasized the deleterious effects of international trade
      agreements on public health and health services. Organizational stakeholders hold
      widely divergent constructions of reality regarding trade, public health, and
      health services. Social constructions concerning trade and health reflect broad
      ideologies concerning the impacts of market processes. Such constructions
      manifest features of "creed," regarding the role of the market in advancing human
      purposes and meeting human needs. Differences in constructions of trade and
      health constrain policies to address the profound changes generated by global
      trade.

PMID- 15955395
TI  - Income inequality and adult nutritional status: anthropometric evidence from a
      pre-industrial society in the Bolivian Amazon.
AB  - Evidence has been accumulated about the adverse effects of income inequality on
      individual health in industrial nations, but we know less about its effect in
      small-scale, pre-industrial rural societies. Income inequality should have modest
      effects on individual health. First, norms of sharing and reciprocity should
      reduce the adverse effects of income inequality on individual health. Second,
      with sharing and reciprocity, personal income will spill over to the rest of the
      community, attenuating the protective role of individual income on individual
      health found in industrial nations. We test these ideas with data from Tsimane'
      Amerindians, a foraging and farming society in the Bolivian Amazon. Subjects
      included 479 household heads (13+ years of age) from 58 villages. Dependent
      variables included anthropometric indices of short-run nutritional status (body
      mass index (BMI), and age- and sex-standardized z-scores of mid-arm muscle area
      and skinfolds). Proxies for income included area deforested per person the
      previous year and earnings per person in the last 2 weeks. Village income
      inequality was measured with the Gini coefficient. Income inequality did not
      correlate with anthropometric indices, most likely because of negative indirect
      effects from the omission of social-capital variables, which would lower the
      estimated impact of income inequality on health. The link between BMI and income
      and between skinfolds and income resembled a U and an inverted U; income did not
      correlate with mid-arm muscle area. The use of an experimental research design
      might allow for better estimates of how income inequality affects social capital
      and individual health.

PMID- 15955396
TI  - Selfhood and social distance: toward a cultural understanding of psychiatric
      stigma in Egypt.
AB  - Psychiatric stigma is a concept that is often used uncritically by policy-makers
      to explain the underutilization of professional psychiatric services in non
      Western societies. Stigma, however, is a multi-determined process manifestations
      and effects of which cannot be viewed separately from the larger social and
      cultural context. The present paper presents the results of a qualitative study
      of psychiatric stigma in Egypt from the perspective of lay respondents. A
      vignette method was used to elicit judgments of social distance and qualitative
      responses to stories depicting psychosis, depression, alcohol abuse and a
      'possession state' from 208 respondents recruited through their places of work.
      The results indicated that while stigma does exist in Egypt, the form that it
      takes must be understood with reference to Egyptian notions of selfhood that
      locate behavioral disturbances in the intersubjective rather than intrapsychic
      realm. On the one hand, individual blame is diffused as responsibility for the
      illness and its cure is placed in the social, not personal (or biological) realm.
      On the other, behavioral disorders that threaten the social fabric of society are
      particularly stigmatized and often met with social rejection.

PMID- 15955397
TI  - Social capital and mental health: an interdisciplinary review of primary
      evidence.
AB  - An interdisciplinary interrogation of primary evidence linking social capital and
      mental health sought to establish: (1) 'quality of evidence' (assessed in terms
      of study design, methods used to address stated questions, rigor of data
      analysis, and logic and clarity of interpretation of results), and (2)
      applicability of the evidence to public health policy and practice with respect
      to mental health. It is found that social capital, a complex and compound
      construct, can be both an asset and a liability with respect to mental health of
      those in receipt of and those providing services and other interventions. The
      most meaningful assessment of social capital or components thereof may examine
      individual access to rather than possession of social capital, a property of
      groups, and therefore an ecological variable. Theoretical advances in research on
      social capital serve to identify mainly two types of social capital: bonding
      (between individuals in a group) and bridging (between groups). Each type of
      social capital has cognitive and/or structural component(s) and may operate at
      micro and/or macro level(s). Effective mental health policy and service provision
      may build or strengthen bridging social capital and benefit from both bonding and
      bridging social capital where either or both exist. Established indicators of
      social capital are amenable to quantitative and qualitative assessment,
      preferably in tandem. However studies that employ combined research design are
      rare or non-existent. Interdisciplinary multi-method investigations and analyses
      are called for in order to unravel mechanisms whereby social capital and mental
      health might be meaningfully associated.

PMID- 15955398
TI  - Neighborhood disorder, psychological distress, and heavy drinking.
AB  - Studies show that residents of disadvantaged neighborhoods drink more heavily
      than residents of more affluent neighborhoods. However, explanations for this
      association are not well developed. Using data collected from a sample of low
      income women with children from Boston, Chicago, and San Antonio, we explore the
      possibility that perceptions of neighborhood disorder encourage heavy drinking.
      Drawing on Conger's (Q. J. Stud. Alcohol 17 (1956) 296) tension reduction
      hypothesis, we propose that the stress of living in a neighborhood characterized
      by problems with drugs, crime, teen pregnancy, unemployment, idle youth,
      abandoned houses, and unresponsive police can be psychologically distressing and
      lead some people to consume alcohol as a means of palliative escape, to regulate
      feelings of anxiety and depression. In support of the tension reduction
      hypothesis, we find that the positive association between neighborhood disorder
      and heavy drinking is largely mediated by anxiety and depression.

PMID- 15955399
TI  - Obtaining sensitive information from a wary population: a comparison of telephone
      and face-to-face surveys of welfare recipients in the United States.
AB  - Recent studies reveal the benefits of technological developments such as audio
      computer assisted self-interviewing (A-CASI) in interview methodology, especially
      for surveys of sensitive behavior and information. However, we believe that the
      selection of mode of administration depends not only on the technology available
      and the behavior of interest, but also on the specific population under study. We
      therefore assess survey mode effects on reported rates of alcohol and drug use
      among welfare recipients, an especially important group for scholars and public
      health agencies. The sample consisted of adult recipients of Temporary Assistance
      to Needy Families (TANF) in Oklahoma, January 2001. Adjusting for demographic
      characteristics, employment, and education, we employ odds ratios to compare 30
      day, 1 year, and lifetime prevalence estimates from telephone and face-to-face
      surveys. Telephone methodology yields similar or higher estimates for lifetime
      prevalence of alcohol, marijuana, and hard drug use and abuse, though lower
      estimates of recent use. We discuss our findings in relation to underfunded
      public health agencies that must efficiently assess and respond to local levels
      of drug abuse and we conclude that mode selection may depend upon the population
      under study.

PMID- 15955400
TI  - Third-party informed consent in research with adolescents: the good, the bad and
      the ugly.
AB  - Third-party informed consent for child and adolescent participation in research
      is a legal requirement that has been questioned by authors who argue that
      children over 10 are fully able to make decisions regarding this matter. The
      extent to which this requirement encumbers survey researches in this age range
      has not been fully reported. In order to understand the reasons for the
      inconsistent use of condoms among adolescent students in Rio de Janeiro, we
      designed a survey based on an anonymous self-reported questionnaire. Two informed
      consent terms were distributed: one for the adolescent and one for the legal
      representative signature. Participation was offered to all students aged 12-18
      attending class at the day of the consent term distribution. Among 906
      distributed legal represents consent terms, 734 (81%) were not returned. The
      final sample probably presented a bias of selection. Researchers must foresee
      third-party consent as a major encumbrance. There is a need for the definition of
      a range of interventions in which the adolescent might have the legal recognition
      of autonomy for decision about his/her voluntary participation.

PMID- 15955401
TI  - Moving beyond the mother-child dyad: women's education, child immunization, and
      the importance of context in rural India.
AB  - The argument that maternal education is critical for child health is commonplace
      in academic and policy discourse, although significant facets of the relationship
      remain empirically and theoretically challenged. While individual-level analyses
      consistently suggest that maternal education enhances child health outcomes,
      another body of literature argues that the observed causality at the individual
      level may, in fact, be spurious. This study contributes to the debate by
      examining the contextual effects of women's education on children's immunization
      in rural districts of India. Multilevel analyses of data from the 1994 Human
      Development Profile Index and the 1991 district-level Indian Census demonstrate
      that a positive and significant relationship exists between the proportion of
      literate females in a district and a child's complete immunization status within
      that district, above and beyond the child's own mother's education as well as
      district-level socioeconomic development and healthcare amenities. However,
      results also indicate that the effect of maternal education cannot be downplayed.
      Thus, increasing women's literacy at the community level, in addition to mother's
      access to higher education-such as matriculation and beyond-at the individual
      level, emerge as effective developmental tools.

PMID- 15955402
TI  - Pregnancy outcomes, site of delivery, and community schisms in regions affected
      by the armed conflict in Chiapas, Mexico.
AB  - The Zapatista armed conflict began in the state of Chiapas, Mexico, in 1994, and
      overlaps pre-existing local disputes about land, religion, and other issues.
      Related disruptions in access to and utilization of health services have been
      alleged to have compromised local health status, particularly in vulnerable
      subgroups such as indigenous women and infants. The study objective was to
      measure maternal and perinatal mortality ratios and utilization of pregnancy
      related health services in the region affected by the Zapatista conflict, and to
      describe associations between these primary outcome measures, socioeconomic and
      demographic factors, and factors associated with inter-party and intra-community
      conflict. A cross-sectional, population-based survey was conducted in 46
      communities in three regions. The study subjects were 1227 women, 13-49 years
      old, who had been pregnant during the preceding 2 years (1999-2001). Principal
      outcome measures were maternal and perinatal mortality, and site of delivery.
      Secondary analyses explored associations between primary outcomes and
      socioeconomic, demographic, and conflict-related factors. Most births (87.1%)
      occurred at home. The crude observed maternal and perinatal mortality ratios were
      607/100,000 and 23.5/1000 live births, respectively. Those who died had
      difficulty accessing emergency obstetrical care. Both home birth and mortality
      were associated with descriptors of intra-community conflict. Observed maternal
      and perinatal mortality ratios were substantially higher than those officially
      reported for Mexico or Chiapas. Reduction of high reproductive mortality ratios
      will require attention to socioeconomic and conflict-related problems, in
      addition to improved access to emergency obstetrical services.

PMID- 15955403
TI  - Physician-patient communication following invasive procedures: an analysis of
      post-angiogram consultations.
AB  - Although rarely studied, physician-patient interactions immediately following
      diagnostic tests are significant medical events because during these encounters
      the physician and patient often make decisions about major and sometimes invasive
      treatment. This investigation analyzed patterns of physician-patient
      communication following coronary angiography with particular attention to
      behaviors important to decision-making: physician information-giving, physician
      use of partnership-building, and active forms of patient participation (e.g.,
      asking questions, being assertive, expressing concerns). We were particularly
      interested in effects related to the patient's race in light of documented
      evidence of racial disparities in cardiac care and outcomes. From audiotape
      recordings, 93 physician-patient interactions after coronary angiogram in a
      catheterization laboratory in a large US Veterans Affairs Medical Center were
      coded to measure the frequency of physicians' information-giving and partnership
      building and the frequency of active patient participation. We also stratified
      these behaviors according to whether the behavior was prompted (e.g., physician
      information in response to a patient's question; a patient's opinion solicited by
      the doctor) or self-initiated. Several findings were noteworthy. First, these
      interactions were very brief and dominated by the physician. Second, although
      physician information-giving increased with more active patient participation,
      which in turn was correlated with physicians' use of partnership-building,
      proportionally little of the physicians' information (8%) and active patient
      participation (9%) was directly prompted by the other interactant. Finally, there
      was a tendency for physicians to self-initiate less information giving to black
      patients and for black patients to self-initiate less active participation than
      white patients. Although these differences were attenuated when other variables
      (e.g., the physician's training, disease severity) were included in the analysis,
      the pattern suggests a potential cycle of passivity where certain patients tend
      to receive fewer informational resources and these patients in turn do less to
      prompt the doctor for more.

PMID- 15955404
TI  - The social structural production of HIV risk among injecting drug users.
AB  - There is increasing appreciation of the need to understand how social and
      structural factors shape HIV risk. Drawing on a review of recently published
      literature, we seek to describe the social structural production of HIV risk
      associated with injecting drug use. We adopt an inclusive definition of the HIV
      'risk environment' as the space, whether social or physical, in which a variety
      of factors exogenous to the individual interact to increase vulnerability to HIV.
      We identify the following factors as critical in the social structural production
      of HIV risk associated with drug injecting: cross-border trade and transport
      links; population movement and mixing; urban or neighbourhood deprivation and
      disadvantage; specific injecting environments (including shooting galleries and
      prisons); the role of peer groups and social networks; the relevance of 'social
      capital' at the level of networks, communities and neighbourhoods; the role of
      macro-social change and political or economic transition; political, social and
      economic inequities in relation to ethnicity, gender and sexuality; the role of
      social stigma and discrimination in reproducing inequity and vulnerability; the
      role of policies, laws and policing; and the role of complex emergencies such as
      armed conflict and natural disasters. We argue that the HIV risk environment is a
      product of interplay in which social and structural factors intermingle but where
      political-economic factors may play a predominant role. We therefore emphasise
      that much of the most needed 'structural HIV prevention' is unavoidably political
      in that it calls for community actions and structural changes within a broad
      framework concerned to alleviate inequity in health, welfare and human rights.

PMID- 15955405
TI  - Decolonization and the movement for institutionalization of Chinese medicine in
      Hong Kong: a political process perspective.
AB  - This paper focuses on the question of why the social and political acceptance of
      Chinese medicine has grown in the former British colony of Hong Kong since the
      late 1980s. To supplement the conventional explanations for the
      institutionalization of alternative medicines, we propose a political process
      perspective that highlights the effects of political changes amidst the
      decolonization process in Hong Kong. During the late 1980s and early 1990s, the
      weakening of the political position of the established elite, the opening up of
      political space for previously excluded groups, and the competition for support
      among the new political elite, all stimulated the indigenous Chinese medicine
      organizations to mobilize for the institutionalization of Chinese medicine. By
      the mid-1990s academics from leading tertiary institutions began to take over the
      leadership of the movement and in doing so carried it to a higher level. In the
      conclusion, we briefly consider the implications of this movement for the future
      development of alternative medicine in Hong Kong and other societies.

PMID- 15955406
TI  - Family, kinship, memory and temporality in the age of the new genetics.
AB  - The new genetics has now become an integral part of contemporary biomedicine,
      promising great advances in alleviating disease. Like any scientific endeavor,
      beliefs in the new genetics tend to give new meanings to people's lives and
      therefore have significant implications for people's lived experience. Drawing on
      fieldwork in the USA and research in various literatures, the aim of this article
      is to explore the role the new genetics plays in mainstream American society as
      revealed in people's narratives of their families' medical histories. An
      anthropological analysis of these narratives illuminates multilayered cultural
      meanings of genetic inheritance and the role biomedical conceptualizations play
      not only in explaining disease etiologies and treatment, but also in addressing
      concerns that bear on the postmodern experience of family, kinship, choice,
      memory, time-space, relatedness, sociality and immortality.

PMID- 15955407
TI  - Mothers, daughters and sexual agency in one low-income South African community.
AB  - Statistics indicate that sexual health problems like HIV/AIDS and teenage
      pregnancies are prevalent among young South African low-income women. To improve
      the effectiveness of preventative programmes for adolescents it is important to
      focus on adolescents' own understanding and experience of their sexual behaviour
      within the contexts in which it occurs. Female adolescents' experiences of their
      own sexuality are shaped by a range of contexts: from the very specific context
      of their intimate relationships to the broader contexts of gender, ethnicity and
      social class. It is therefore imperative to adopt a research approach that
      stratifies groups and develops interventions that are based on the needs,
      interests, sexual beliefs and behaviours of specific communities rather than
      developing general educational messages. The current paper is part of a larger
      study exploring female adolescent sexuality in a South African low-income rural
      coloured community. Twenty-five adolescent coloured women aged 14-18 years were
      interviewed about how they viewed their sexuality. The grounded theory analysis
      indicated that the participants demonstrated a limited sense of sexual agency in
      these constructions of their sexuality. The mothers of these young women were
      powerful agents in the young womens' constructions of their own sexuality and
      they unintentionally contributed to their daughters' limited sense of sexual
      agency. Mothers presented sex as a dangerous activity to their daughters. This
      discourse of sex as danger contributed towards a mutual understanding that sex
      should not be talked about. Daughters' deception of their mothers about their
      sexual activity maintained mother-daughter connections, but left them without an
      interactional space where they could talk freely to their mothers about
      sexuality.

PMID- 15955408
TI  - Expectations regarding length and health related quality of life: some empirical
      findings.
AB  - Own expectations regarding length and future quality of life can differ from
      objective measures such as actuarial life expectancy. If so, this may have
      implications for health behaviour, seeking medical care and for methods used in
      health economic research. In this paper, we present evidence on own expectations
      regarding length and quality of life, using data obtained from a Dutch
      convenience sample (n=600). Data were obtained through a written questionnaire
      and a web-based survey. Own expectations regarding future quality of life were
      obtained by using the EQ-5D descriptive system on which respondents could
      indicate expected health profiles for the ages 60-90. We find that respondents
      significantly overestimate life expectancy (by 4.1 years, males 7.0 years and
      females 1.7 years), but appear to underestimate future quality of life from the
      age 70 onward. Regression analysis is used to explain individual expectations.
      Age, current health status and the perception of current lifestyle are especially
      important explanatory variables of people's own expectations regarding length and
      quality of life. Average age of death of relatives moreover explains self
      estimated life expectancy, whereas self-estimated life expectancy explains
      expectations regarding quality of life. Given the influence inaccurate
      expectations may have on actual behaviour, more research on own expectations and
      their relation with actual behaviour is needed.

PMID- 15955409
TI  - Men, sport, spinal cord injury, and narratives of hope.
AB  - Drawing on data from a life history study of a small group of men who have
      suffered spinal cord injury and become disabled through playing sport, this
      article explores the meanings of hope in their lives. It focuses upon the life
      stories of 14, white, predominantly working-class men, aged 26-51. The most
      common kinds of hope used by the men were shaped by three powerful narrative
      types that circulate in Western cultures. These were 'concrete hope' (the most
      common form), shaped by the restitution narrative; 'transcendent hope', shaped by
      the quest narrative; and 'despair' or loss of any kind of hope, shaped by the
      chaos narrative. The implications of this dynamic process for their identity
      reconstruction as disabled men are considered.

PMID- 15955410
TI  - 'That's like chopping off a finger because you're afraid it might get broken':
      disease and illness in women's views of prophylactic mastectomy.
AB  - While data are accumulating on the efficacy of prophylactic mastectomy as a means
      to reduce breast cancer risk in high risk women, the effectiveness of the
      procedure depends on women's interest in undergoing the procedure. We report on
      women's responses to this surgical option as a prevention tool. Data derive from
      a multi-method study of women's interest in and understandings about genetic
      testing for breast cancer susceptibility. The sample comprises 246 women of
      varying ethnicities and familial breast cancer risk from Seattle, USA. In this
      paper, quantitative data are presented on the sociodemographic and risk
      perception correlates of degree of interest in taking a genetic test for breast
      cancer if prophylactic mastectomy were the only treatment option. In addition, we
      report results of a content analysis of women's open-ended responses to the
      question of whether and why they could imagine undergoing prophylactic
      mastectomy. Our analysis of these data benefits from a central distinction in
      medical anthropology between the concepts of illness and disease. We suggest that
      while prophylactic mastectomy may prevent the "disease" of breast cancer, it may
      be of little interest to women who see this surgery as itself mimicking the
      "illness" of breast cancer.

PMID- 15955411
TI  - Protective effect of serofendic acid on glutamate-induced neurotoxicity in rat
      cultured motor neurons.
AB  - We have previously reported that a sulfur-containing neuroprotective substance
      named serofendic acid was purified and isolated from lipophilic extract of fetal
      calf serum (FCS). In the present study, we investigated the effect of serofendic
      acid on glutamate neurotoxicity using embryonic rat spinal cord culture. When
      cultures were exposed to glutamate (20 microM) with a glutamate transporter
      inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC; 40 microM) for 24 h, motor
      neurons were injured through both N-methyl-D-aspartate and alpha-amino-3-hydroxy
      5-methylisoxazole/kainate receptors. This glutamate neurotoxicity was attenuated
      by nitric oxide (NO) synthase inhibitors. Serofendic acid (0.1-5 microM)
      prevented glutamate neurotoxicity in a concentration-dependent manner. S
      Nitrosocysteine (SNOC; 10 microM), an NO donor, induced motor neuronal death.
      Serofendic acid (5 microM) also prevented SNOC-induced neurotoxicity. These
      results indicate that serofendic acid protects cultured motor neurons from
      glutamate neurotoxicity by reducing the cytotoxic action of NO.

PMID- 15955412
TI  - High- and low-affinity binding of S-citalopram to the human serotonin transporter
      mutated at 20 putatively important amino acid positions.
AB  - The serotonin transporter (SERT) is responsible for terminating or modulating the
      action of serotonin released from the presynaptic neuron and is the major target
      for most antidepressants including the tricyclic antidepressants and the
      selective serotonin uptake inhibitors. Two binding sites for uptake inhibitors
      and serotonin (5-HT) have been found on SERT. At one site, uptake inhibitors bind
      with high-affinity to SERT, thereby blocking the uptake of 5-HT. The other site
      is a low-affinity allosteric site, which influences the dissociation of uptake
      inhibitors, such as imipramine, paroxetine, and citalopram from the first site,
      when occupied by 5-HT and a few uptake inhibitors like paroxetine and citalopram.
      In this study, the connection between the high-affinity binding site and the
      allosteric affinity-modulating site was investigated by introducing 20 single
      amino acid substitutions into positions of presumed importance. Binding of S
      citalopram, both to the high-affinity-binding site and to the allosteric binding
      site, was measured in these mutants with the purpose of investigating the
      connection between the two binding sites. The amino acid substitutions did not
      introduce large changes in the two binding sites, but the results indicate that
      the two binding sites are independent as mutants were found in which the two
      binding sites were affected differently. Mutations were found which destabilised
      the high-affinity binding without changing the allosteric effect (e.g., G128A);
      mutations which destabilised the high-affinity binding but increased the
      allosteric effect (e.g., G100A), and mutations which were without effect on the
      high-affinity binding, but which increased the allosteric effect (e.g., Q562A).
      It is concluded that the allosteric binding site is independent of the high
      affinity-binding site; it may therefore represent a new drug target.

PMID- 15955413
TI  - Cocaine pre-exposure enhances CRF-induced expression of c-fos mRNA in the central
      nucleus of the amygdala: an effect that parallels the effects of cocaine pre
      exposure on CRF-induced locomotor activity.
AB  - There is evidence that cocaine pre-exposure produces changes in the responsivity
      of central corticotropin-releasing factor (CRF) systems and that these systems
      mediate some of the drug-related behavioural effects of acute stressors. The
      present experiment was conducted to assess the effects of repeated cocaine
      exposure on CRF-induced neuronal activation within two regions of the extended
      amygdala, the central nucleus of the amygdala (CeA) and lateral bed nucleus of
      the stria terminalis (BNST). In addition, CRF-induced neuronal activation was
      compared with CRF-induced locomotor activity. Rats were injected for 7 days with
      cocaine (days 1 and 7 in test chambers; days 2-6 in homecages) or saline. After
      10 drug-free days, locomotor responsiveness to intracerebroventricular (i.c.v.)
      injections of CRF and Vehicle was assessed over 2-h test periods. Twenty-four to
      48 h following testing for locomotor activity, animals were injected with either
      CRF or Vehicle, 30 min before being sacrificed. Subsequently, the brains were
      processed by in situ hybridization for c-fos mRNA, a widely used marker of
      neuronal activation, in the CeA and BNST. In CeA, i.c.v. CRF enhanced the
      expression of c-fos mRNA in cocaine, but not saline, pre-exposed animals; in the
      same animals, i.c.v. CRF resulted in enhanced locomotor activity in cocaine, but
      not saline, pre-exposed animals. The results demonstrate that repeated exposure
      to cocaine changes the neuronal response to CRF in the CeA; furthermore, they
      suggest that these changes in the CeA could potentially be of functional
      significance in the effects of repeated cocaine exposure on CRF-induced locomotor
      activity.

PMID- 15955414
TI  - Tyramine-immunoreactive neuronal structures in the rat brain: abundance in the
      median eminence of the mediobasal hypothalamus.
AB  - Immunoreactivity to p-tyramine, one of the natural trace amines, was studied in
      the rat brain by an anti-p-tyramine antibody. Immunoreactivity to this amine is
      very weak in the nigrostriatal dopaminergic neurons and terminals, and weak in
      the locus coeruleus noradrenergic ones. It was intensified in these structures
      after monoamine oxidase inhibition. On the other hand, this amine was highly
      concentrated in the median eminence of the mediobasal hypothalamus, in which its
      physiological function on prolactin release has been demonstrated.

PMID- 15955415
TI  - Mutation screen of GABRA1, GABRB2 and GABRG2 genes in Japanese patients with
      absence seizures.
AB  - Absence seizures are classified into typical and atypical absences according to
      clinical and EEG characteristics. Although missense mutations in the GABA(A)
      receptor gamma2 subunits (GABRG2) gene have recently been detected in two
      families with typical absence seizures, no study has been carried out to clarify
      the relationship between atypical absence and GABA(A) receptors. We performed
      mutation analysis of all the coding exons of GABA(A) receptor alpha1, beta2 and
      gamma2 subunit (GABRA1, GABRB2 and GABRG2) genes by direct sequencing to clarify
      whether there was common molecular biological mechanism underlying both typical
      and atypical absences. We recruited 52 unrelated Japanese patients, thirty-eight
      with typical absences and 14 with atypical absences. They consisted of 38 with
      childhood absence epilepsy, three with Lennox-Gastaut syndrome, two with epilepsy
      with myoclonic-astatic seizures and nine with epilepsy with continuous spike
      waves during slow wave sleep. All of the subjects were idiopathic or cryptogenic
      cases without any organic brain lesions or underlying diseases. We detected five
      polymorphisms (T156C in GABRA1, C1194T in GABRB2, and C315T, T588C and C1230T in
      GABRG2), and they are silent mutations. In conclusion, mutations in GABRA1,
      GABRB2 and GABRG2 do not seem to be a major genetic cause of epilepsy with
      typical and atypical absences in Japanese subjects.

PMID- 15955417
TI  - The role of norepinephrine and nitric oxide in activities of rat arginine
      vasopressin neurons in response to immune challenge.
AB  - To explore the potential role of norepinephrine (NE) and nitric oxide (NO) in
      activities of rat hypothalamus arginine vasopressin (AVP) neurons in response to
      immune challenge, we observed the effect of prazosin, an antagonist of alpha1
      adrenergic receptor, and the specific nitric oxide synthase (NOS) inhibitor
      N(w)nitro-L-arginine-methylester (L-NAME) on the Fos expression in AVP neurons
      induced by systemic lipopolysaccharide (LPS) using double immunohistochemistry.
      Intravenous (i.v.) injection of LPS induced Fos expression in AVP neurons mainly
      in the hypothalamus paraventricular nucleus (PVN) and in the supraoptic nucleus
      (SON). The percentage of Fos-positive AVP neurons was dose-dependent.
      Pretreatment with prazosin (5 mg/kg) effectively suppressed the Fos expression
      induced by LPS (5 microg/kg), whereas L-NAME (30 mg/kg) did not influence the Fos
      expression in the AVP neurons induced by LPS (0.25, 0.5, 1, 5 microg/kg). Our
      results suggest that the activation of central AVP neurons caused by systemic LPS
      may be mediated by NE through alpha1-adrenergic receptors, but could not be
      changed by NO.

PMID- 15955416
TI  - Development, characterisation and epitope mapping of novel monoclonal antibodies
      for DJ-1 (PARK7) protein.
AB  - Mutations in DJ-1 (PARK7) were recently identified as the cause for an autosomal
      recessive early onset form of familial Parkinson's disease, however, the function
      of the protein in the brain is yet to be elucidated. Here we report on the
      development, characterisation and epitope mapping, of two novel monoclonal
      antibodies to DJ-1. One of them (DJ-1 "clone16") has its epitope between amino
      acids 56-78 of the human DJ-1 protein and has very similar properties to a
      commercially available DJ-1 antibody clone 3E8. The second antibody recognised
      both the rat and human DJ-1 (DJ-1 "clone 48") and its epitope is between amino
      acids 26-56. We have used immunohistochemistry with these two antibodies to
      compare the distribution of DJ-1 in human and rat brain tissue. Both antibodies
      gave similar patterns of labelling in human brain with marked astrocytic
      expression. Neuronal labelling was weak or absent and the antibodies did not
      label Lewy bodies or Lewy neurites. In the rat brain, DJ-1 was ubiquitously
      expressed in neurones but exhibited low expression in astrocytes. These
      antibodies could be exploited as important tools in dissecting out DJ-1
      expression in different species and examination of the role of DJ-1 in
      Parkinson's disease.

PMID- 15955419
TI  - Reliability of a practicable EMG-moment model for antagonist moment prediction.
AB  - Although the use of practicable EMG-moment models for knee joint moment
      prediction appears promising, the repeatability of the estimated forces remains
      unclear. The purpose of this study was to apply an EMG-moment model to predict
      the antagonist moment of the knee flexors (Mflx) during maximal isometric knee
      extension efforts. Nine healthy males performed maximal isometric knee extension
      and flexion contractions at 0 degrees , 45 degrees and 90 degrees angles with
      recordings of the net moment and EMG of thigh muscles. Calibration knee flexion
      efforts were performed at different levels of intensity and the resulting EMG
      moment curves were fitted using second-order polynomials. The polynomials were
      then used to predict Mflx. This procedure was repeated a week after. The results
      indicated non-significant differences in test-retest Mflx. Intraclass correlation
      coefficients ranged from 0.852 to 0.912 indicating high test-retest reliability
      of the estimated Mflx. For isometric contractions, the present model is suitable
      as a method to estimate antagonist muscle moments.

PMID- 15955418
TI  - TMS-responses during anticipatory postural adjustment in bimanual unloading in
      humans.
AB  - Transcranial magnetic brain stimulation (TMS) was used to assess the influence of
      the corticospinal system on motor output during forearm unloading in humans.
      Unloading was obtained either "passively" by the experimenter, or "actively" with
      the subjects' own contralateral arm. Anticipatory postural adjustments consisted
      of changes in the activity of a forearm flexor muscle prior to active unloading
      of the limb and acted to stabilize the forearm position. Motor evoked potentials
      (MEPs) were recorded in the forearm flexor at different times during active and
      passive unloading, static forearm loading, and during lifting of an equivalent
      weight by the contralateral arm while the ipsilateral forearm was statically
      loaded and held stationary. In active unloading, MEP amplitude decreased with the
      decrease of muscle activity. Passive unloading resulted in a similar decrease of
      MEP as with active unloading. During stationary forearm loading, the change in
      MEP corresponded to the degree of loading. If during static loading the
      contralateral arm has lifted a separate, equivalent weight, the amplitude of MEP
      decreased. A possible role of direct corticospinal volley and the motor command
      mediated by subcortical structures in anticipatory postural adjustments is
      discussed.

PMID- 15955420
TI  - Immunohistochemical and immunoblot analysis of gamma-aminobutyric acid B receptor
      in the prefrontal cortex of subjects with schizophrenia and bipolar disorder.
AB  - Immunohistochemical and immunoblot techniques were employed to examine the
      distribution and expression of GABA(B) receptors in the prefrontal cortex of
      postmortem subjects with schizophrenia and bipolar disorder. GABA(B)R1a/b
      immunoreactivity was observed in the neuronal soma and dendrites as well as in
      the neuropil in the control subjects. GABA(B)R1a/b immunolabeling in neurons from
      the subjects with schizophrenia and bipolar disorder was less intense than in
      those from the control subjects. In control subjects, the distribution of
      GABA(B)R2 immunoreactivity was found to be similar to that of GABA(B)R1a/b.
      GABA(B)R2 immunolabeling in neurons from the bipolar disorder group appeared less
      intense than that of the normal controls as well as that in schizophrenic groups.
      Immunoblot analysis demonstrated a significant decrease in GABA(B)R1a levels in
      schizophrenic subjects, while there was a significant decrease in GABA(B)R1a,
      GABA(B)R1b, and GABA(B)R2 levels in bipolar subjects compared with the controls.
      The present study suggests that the GABA(B) receptor is involved in the
      pathophysiology of schizophrenia and bipolar disorder, and further suggests that
      the patterns of changes in GABA(B) receptor subtypes are different between these
      two disorders.

PMID- 15955421
TI  - Chronic-stress induced modulation of different states of anxiety-like behavior in
      female rats.
AB  - Stress facilitates emotionality and consolidation of aversive memories in male
      rodents. In addition, considerable sexual dimorphism has been observed in animal
      and clinical literature, both in response to stress and predisposition to anxiety
      disorders thought to be exacerbated by stress. In view of this, we investigated
      effects of chronic immobilization stress and chronic unpredictable stress on
      anxiety-like behavior exhibited by female Wistar rats, using the elevated plus
      maze. Neither of the stress paradigms employed in this study significantly
      influenced anxiety, as manifested by similar open-arm exploration in control and
      treated animals. Previous studies have reported that in males, exposure to
      elevated plus-maze during an initial trial significantly reduces open-arm
      exploration in subsequent retesting, an effect attributed to consolidation of
      aversive experience of the initial exposure. Control female animals, during a
      second exposure to the maze 72 h after the first trial, displayed a similar shift
      to a state of enhanced anxiety. Furthermore, exposure to stress did not affect
      such consolidation of anxiety, as evidenced by similar reduction in open-arm
      exploration between control and stressed animals during retesting. We conclude
      that female rats are insensitive to chronic stress in terms of facilitation and
      consolidation of anxiety.

PMID- 15955422
TI  - Human auditory event-related potentials predict duration judgments.
AB  - Internal clock models postulate a pulse accumulation process underlying timing
      activities, with more accumulated pulses resulting in longer perceived durations.
      We investigated whether this accumulation is reflected in the amplitude of event
      related brain potentials (ERPs) elicited by auditory stimuli with durations of
      400-600 ms. In a duration discrimination paradigm, we found more negative
      amplitudes to physically identical stimuli when they were judged as longer than
      the memorized standard duration (500 ms) as compared to being classified as
      shorter. This sustained negativity was already developing during the first 100 ms
      after stimulus onset. It could not be explained as a bias to respond with a
      particular hand (lateralized readiness potential), but rather reflects a
      processing difference between the tones to be judged as shorter or longer. Our
      results are in line with models of time processing which assume that higher
      numbers of accumulated pulses of a temporal processor result in an increase in
      perceived duration.

PMID- 15955423
TI  - Activation of melanocortin receptors accelerates the gonadotropin-releasing
      hormone pulse generator activity in goats.
AB  - The present study aims to elucidate whether the central melanocortin receptors
      [melanocortin-3 and -4 receptors (MC3/4-R)] are involved in regulating GnRH pulse
      generator activity in female goats. The GnRH pulse generator activity was
      electrophysiologically assessed at the intervals of characteristic increases in
      multiple-unit activity (MUA volleys) in the mediobasal hypothalamus. In
      ovariectomized goats, all doses (0.02, 0.2 and 2 nmol) of MT II, an MC3/4-R
      agonist, injected into the lateral ventricle significantly shortened MUA volley
      intervals. The duration of the period during which MT II accelerated MUA volleys
      was positively correlated with the dose of MT II injected. The stimulatory effect
      of MT II on the GnRH pulse generator activity was attenuated in the presence of
      estrogen. Intracerebroventricular injection of SHU9119, an MC3/4-R antagonist,
      significantly prolonged MUA volley intervals at 1 nmol. MT II (0.2 nmol)-induced
      acceleration of MUA volleys was partially blocked by the antagonism of MC3/4-R
      with pre-administered SHU9119 (1 nmol). The present findings demonstrate that
      MC3/4-R are involved in maintaining GnRH pulse generator activity in goats.

PMID- 15955424
TI  - Rejuvenation of antioxidant system in central nervous system of aged rats by
      grape seed extract.
AB  - Oxidative stress is considered as a major risk factor that contributes to age
      related increase in lipid peroxidation and declined antioxidants in the central
      nervous system during aging. Grape seed extract, one of the bioflavonoid, is
      widely used for its medicinal properties. In the present study, we evaluated the
      role of grape seed extract on lipid peroxidation and antioxidant status in
      discrete regions of the central nervous system of young and aged rats. Male
      albino rats of Wistar strain were divided into four groups: Group I-control young
      rats, Group II-young rats treated with grape seed extract (100 mg/kg body weight)
      for 30 days, Group III-aged control rats and Group IV-aged rats supplemented with
      grape seed extract (100 mg/kg body weight) for 30 days. Age-associated increase
      in lipid peroxidation was observed in the spinal cord, cerebral cortex, striatum
      and the hippocampus regions of aged rats (Group III). Activities of antioxidant
      enzymes like superoxide dismutase, catalase, glutathione peroxidase and levels of
      non-enzymic antioxidants like reduced glutathione, Vitamin C and Vitamin E were
      found to be significantly decreased in all the brain regions studied in aged rats
      when compared to young rats. However, normalized lipid peroxidation and
      antioxidant defenses were reported in the grape seed extract-supplemented aged
      rats. These findings demonstrated that grape seed extract enhanced the
      antioxidant status and decreased the incidence of free radical-induced lipid
      peroxidation in the central nervous system of aged rats.

PMID- 15955425
TI  - Mutations in the hemochromatosis gene (HFE) and multiple sclerosis.
AB  - In the present study we have investigated whether HFE gene polymorphism may play
      a role in the disease process of Croatian and Slovenian MS patients and their
      potential genetic susceptibility to MS. We genotyped 314 MS patients and 400
      healthy controls for the C282Y and H63D mutations by polymerase chain
      reaction/restriction fragment length polymorphism (PCR-RFLP) analysis. Our
      results showed no significant differences in the distribution of the two
      mutations between MS patients and controls, suggesting that HFE polymorphisms do
      not contribute to the susceptibility to MS. Also, there was no significant
      correlation between HFE polymorphism and the disease progression index. However,
      we observed that MS patients carrying the mutant C282Y allele exhibited earlier
      onset of disease symptom relative to other genotypes, but it warrants further
      study in a larger series of MS patients.

PMID- 15955426
TI  - TrkA NGF receptor plays a role in the modulation of p75NTR expression.
AB  - The cellular response to nerve growth factor (NGF) is mediated by two
      structurally unrelated receptors, TrkA and p75 neurotrophin receptor (p75NTR),
      which have been shown to interact resulting in reciprocal modulation of function.
      In this study, we have examined the modulation of p75NTR protein expression by
      specific TrkA autophosphorylation sites in the presence or absence of NGF. We
      have used cell lines derived from PC12 cells that express either no endogenous
      TrkA (PC12nnr5) or TrkA receptors mutated via site-directed mutagenesis to
      abrogate individual tyrosine autophosphorylation sites on the cytoplasmic tail
      (Y490F, Y785F and Y490/785F). Results indicate that in the absence of TrkA in
      PC12nnr5 cells there is reduced constitutive p75NTR expression, which can be
      restored to different degrees by transfection of the Y490F TrkA or the Y490/785F
      TrkA, but not by transfection of the Y785F TrkA. In addition, the expression of
      p75NTR was upregulated in the presence of NGF in the parental and Y490F cell
      lines only. Together these results indicate a role for the individual tyrosine
      autophosphorylation sites of TrkA in regulating p75NTR expression.

PMID- 15955427
TI  - Auditory evoked fields to variations of interaural time delay.
AB  - Auditory motion can be simulated by presenting binaural sounds with time-varying
      interaural time delays. Human cortical responses to the rate of auditory motion
      were studied by recording auditory evoked magnetic fields with a 122-channel
      whole-head magnetometer. Auditory motion from central to right and then to
      central was produced by varying interaural time differences between ears. The
      results showed that the N1m latencies and amplitudes were not affected by the
      fluctuation of interaural time delay; however, the peak amplitude of P2m
      significantly increased as a function of fluctuation of the interaural time
      delay.

PMID- 15955428
TI  - Role of GABA in electro-acupuncture therapy on cerebral ischemia induced by
      occlusion of the middle cerebral artery in rats.
AB  - This study investigated the possible involvement of gamma-aminobutyric acid
      (GABA) in the therapeutic effect of cerebral ischemia by electro-acupuncture (EA)
      using the rat model with middle cerebral artery occlusion (MCAO). By
      immunohistochemistry, the changes of GABA expression level in the primary infarct
      area and its penumbral regions were examined. The changes in infarct area and
      survival neuron percentages were also assessed using haematoxylin and eosin
      stained sections after picrotoxin (PTX) injection, a GABA receptor's antagonist.
      Our results showed that EA markedly decreased the ischemic damaged areas in the
      cerebral cortex and hippocampus. Concomitant to this was an up-regulation of GABA
      immunoexpression in MCAO rats with EA treatment (P < 0.05). Furthermore,
      injection of PTX in rats subjected to MCAO or MCAO followed by EA treatment
      increased the infarct area and decreased survival cell percentage significantly
      when compared with those without PTX injection. In the light of these findings,
      it is suggested that EA on specific and established acupoints that are commonly
      used in clinical management of cerebral ischemia may have elicited an up
      regulated expression of GABA that would have a neuroprotective effect.

PMID- 15955429
TI  - Normalization of hypothalamic serotonin (5-HT 1B) receptor and NPY in cancer
      anorexia after tumor resection: an immunocytochemical study.
AB  - Tumor growth leads to anorexia and decreased food intake, the regulation of which
      is via the integrated hypothalamic peptidergic and monoaminergic system.
      Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in
      hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We
      previously reported that 5-HT 1B-receptors are up regulated while NPY is down
      regulated in tumor-bearing (TB)-related anorexia, contributing to food intake
      reduction. In anorectic TB rats we hypothesize that after tumor resection when
      food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY
      will occur. The aim of this study was to demonstrate normalization of these
      hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after
      tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT
      1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase
      antiperoxidase immunocytochemical methods. Image analysis of immunostaining was
      performed and the data were statistically analyzed. Immunostaining specificity
      was controlled by omission of primary or secondary antibodies and pre-absorption
      test. Our results show that after TB-R versus Controls a normalization of food
      intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These
      data, discussed in context with our previous studies, support the hypothesis that
      tumor resection results not only in normalization of food intake but also in
      reversible changes of anorectic and orexigenic hypothalamic modulators.

PMID- 15955431
TI  - Troubleshooting poor reproductive performance in large herds.

PMID- 15955432
TI  - Reproductive record analysis.

PMID- 15955433
TI  - Nutrition and reproduction in dairy herds.

PMID- 15955434
TI  - Breeding strategies to optimize reproductive efficiency in dairy herds.

PMID- 15955435
TI  - Breeding strategies to optimize reproductive efficiency in beef herds.

PMID- 15955436
TI  - Venereal diseases of cattle: natural history, diagnosis, and the role of vaccines
      in their control.

PMID- 15955437
TI  - The effect of semen quality on reproductive efficiency.

PMID- 15955438
TI  - Potential applications and pitfalls of reproductive ultrasonography in bovine
      practice.

PMID- 15955439
TI  - Embryonic death in cattle.

PMID- 15955440
TI  - Diagnosis of fetal loss caused by bovine viral diarrhea virus and Leptospira spp.

PMID- 15955441
TI  - Neosporosis in cattle.

PMID- 15955442
TI  - Management of transition cows to optimize reproductive efficiency in dairy herds.

PMID- 15955443
TI  - Management of periparturient disorders in dairy cattle.

PMID- 15955444
TI  - A rational basis for therapy in the sick postpartum cow.

PMID- 15955445
TI  - Reducing calf losses in beef herds.

PMID- 15955447
TI  - Reduced urinary excretion of sulfated polysaccharides in diabetic rats.
AB  - The aim of the present study was to further understand the changes in renal
      filtration that occur in the early stages of diabetes mellitus. Diabetes was
      induced in male Wistar rats by a single injection of streptozotocin. Glycemia,
      body weight, 24-h urine volume and urinary excretion of creatinine, protein and
      glycosaminoglycans were measured 10 and 30 days after diabetes induction. All the
      diabetic animals used in the present study were hyperglycemic, did not gain
      weight, and presented proteinuria and creatinine hyperfiltration. In contrast,
      the glycosaminoglycan excretion decreased. Dextran sulfates of different
      molecular weights (6.0 to 11.5 kDa) were administered to the diabetic rats, and
      to age-matched, sham-treated controls. Most of the dextran sulfate was excreted
      during the first 24 h, and the amounts excreted in the urine were inversely
      proportional to the dextran sulfate molecular weight for all groups.
      Nevertheless, diabetic rats excreted less and accumulated more dextran sulfate in
      kidney and liver, as compared to controls. These differences, which were observed
      only for the dextran sulfates of higher molecular weights (>7 kDa), increased
      with the duration of diabetes. Our findings suggest differential renal processing
      mechanisms for proteins and sulfated polysaccharides, with the possible
      involvement of kidney cells.

PMID- 15955446
TI  - Expression of cell survival/death genes: Bcl-2 and Bax at the rate of colon
      cancer prognosis.
AB  - The rate of tumour growth is dependent on the balance between proliferation and
      apoptosis at all stages of carcinogenesis. Apoptosis inhibition, in turn, depends
      partly on the balance between expression of two cell death regulatory genes, Bcl
      2 and Bax. Colon cancer has long been associated with disturbances in apoptosis
      regulation. The aim of our study was to determine the expression levels of Bcl-2
      and Bax mRNAs in 1 microg sample of total RNA obtained from normal colon and
      colon adenocarcinoma. This study was intended to evaluate possible differences in
      Bcl-2 and Bax mRNA levels at particular stages of colon adenocarcinoma classified
      according to Duke's system. The apoptotic frequency (represented by Bax mRNA copy
      number) was inversely proportional to the decrease of Bcl-2 gene expression.
      Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was
      performed to confirm apoptosis.

PMID- 15955448
TI  - Dermal fibroblasts from pseudoxanthoma elasticum patients have raised MMP-2
      degradative potential.
AB  - Cultured fibroblasts from the dermis of normal subjects and of Pseudoxanthoma
      elasticum (PXE) patients were analysed for enzyme activity, protein and mRNA
      expression of metalloproteases (MMP-2, MMP-3, MMP-9, MT1-MMP) and of their
      specific inhibitors (TIMP-1, TIMP-2 and TIMP-3). MMP-3, MMP-9 and TIMP-3 mRNAs
      and proteins failed to be detected in both the medium and the cell layer of both
      controls and PXE patients. MMP-2 mRNA was significantly more expressed in PXE
      than in control cell lines, whereas MT1-MMP, TIMP-1 and TIMP-2 mRNAs appeared
      unchanged. MMP-2 was significantly higher in the cell extracts from PXE
      fibroblasts than in control cells, whereas differences were negligible in the
      cell medium. Data suggest that PXE fibroblasts have an increased proteolytic
      potential, and that MMP-2 may actively contribute to connective tissue
      alterations in this genetic disorder.

PMID- 15955449
TI  - HIV-1 interaction with human mannose receptor (hMR) induces production of matrix
      metalloproteinase 2 (MMP-2) through hMR-mediated intracellular signaling in
      astrocytes.
AB  - Astrocytes are susceptible to HIV-1 infection. We have recently demonstrated that
      human mannose receptor (hMR) is directly involved in CD4-independent HIV-1
      infection of astrocytes. The apparent paradox between the vivid binding affinity
      of HIV-1 gp120 protein to hMR and the low efficiency of hMR-mediated HIV-1
      infection raises the possibility that HIV-1 binding to hMR alone may negatively
      affect astrocyte function. In this study, we examined the relationship between
      HIV-1 interaction with hMR and the production of matrix metalloproteinases (MMPs)
      in astrocytes. We took advantage of an astroglial cell line U87.MR stably
      expressing hMR as an in vitro astrocyte model system and human primary
      astrocytes, and demonstrated that HIV-1 binding to astrocytes induced the
      production of MMP-2. This induction appeared to be most potent with M-tropic HIV
      1 viruses. Increased MMP-2 production was not due to hMR-mediated HIV-1 entry
      and/or HIV-1 viral gene expression, as the transfection of HIV-1 proviral DNA did
      not result in MMP-2 production, and the infection of AT-2-treated HIV-1 viruses
      did not inhibit MMP-2 production. Direct involvement of hMR in HIV-induced MMP-2
      production was confirmed by the inhibition of the yeast mannan, an hMR ligand
      antagonist, and an anti-hMR serum. Furthermore, HIV-induced MMP-2 production in
      astrocytes was shown to involve hMR-mediated intracellular signaling. Taken
      together, these results suggest that HIV-1 binding to astrocytes in the absence
      of HIV-1 viral entry is sufficient to alter astrocyte function through hMR
      mediated intracellular signaling. In addition, these results provide new evidence
      to support the notion that hMR is capable of eliciting intracellular signaling
      upon ligand binding.

PMID- 15955450
TI  - The hepatitis B virus X protein up-regulates lymphotoxin alpha expression in
      hepatocytes.
AB  - Hepatitis B virus X protein (HBx) is involved in intrahepatic inflammatory
      processes by inducing several pro-inflammatory cytokines. It has been suggested
      that these inflammatory processes play an important role in causing
      hepatocarcinogenesis. In this study, we investigated the role of HBx in the
      expression of lymphotoxin alpha (LTalpha) in hepatoma cells such as Huh-7 and
      Chang. Our experiments showed that (i) transient HBx expression in Huh-7 cells up
      regulated LTalpha mRNA expression; (ii) this up-regulation was predominantly
      affected by HBx-induced nuclear factor-kappaB (NF-kappaB) activation. In
      addition, the HBx-induced NF-kappaB activation was decreased by the treatment of
      LTalpha neutralizing antibodies in a dose-dependent manner. We conclude that HBx
      up-regulates LTalpha expression at the transcriptional level through an NF-kappaB
      dependent mechanism and, therefore, the up-regulated LTalpha may be secreted and
      involved in the HBx-induced NF-kappaB activation.

PMID- 15955451
TI  - Cloning, characterization and DNA immunization of an Onchocerca volvulus
      glyceraldehyde-3-phosphate dehydrogenase (Ov-GAPDH).
AB  - In the search for Onchocerca volvulus antigens possibly involved in protection
      against human onchocerciasis, partial amino acid sequence analysis of one of the
      O. volvulus antigens of the serologically identified proteins showed a close
      relationship to the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein
      family. Subsequent adult worm cDNA library screening and cloning produced a clone
      of 1650 bp. An open reading frame spans over 1020 bp encoding for a protein of
      340 amino acids with an apparent molecular weight of 38000. Comparison of the
      complete amino acid sequence identified this protein as a member of the GAPDH
      protein family. The recombinantly expressed protein shows GAPDH enzymatic
      activity as well as plasminogen-binding capacity. DNA sequence analysis of the
      corresponding gene revealed the presence of two introns. Using immunohistology Ov
      GAPDH was observed in microfilariae, infective larvae, and adult male and female
      worms. Most striking was the labelling of the musculature of the body wall.
      Labelling was also observed in the pseudocoeloma cavity and in a subset of cell
      nuclei, suggesting additional, non-glycolytic functions of the Ov-GAPDH. Gene gun
      immunization with the DNA-construct in cattle led to specific humoral immune
      responses. Thus, the protective potential of the DNA-construct of Ov-GAPDH can be
      evaluated in vaccination trials using animal models such as the cattle/Onchocerca
      ochengi model.

PMID- 15955452
TI  - Elevated formation of pyridinoline cross-links by profibrotic cytokines is
      associated with enhanced lysyl hydroxylase 2b levels.
AB  - The hallmark of fibrosis is the excessive accumulation of collagen. The deposited
      collagen contains increased pyridinoline cross-link levels due to an
      overhydroxylation of lysine residues within the collagen telopeptides. Lysyl
      hydroxylase 2b (LH2b) is the only lysyl hydroxylase consistently up-regulated in
      several forms of fibrosis, suggesting that an enhanced LH2b level is responsible
      for the overhydroxylation of collagen telopeptides. The present paper reports the
      effect of profibrotic cytokines on the expression of collagen, lysyl hydroxylases
      and lysyl oxidase in normal human skin fibroblasts, as well as the effect on
      pyridinoline formation in the deposited matrix. All three isoforms of TGF-beta
      induce a substantial increase in LH2b mRNA levels, also when expressed relatively
      to the mRNA levels of collagen type I alpha2 (COL1A2). The TGF-beta isoforms also
      clearly influence the collagen cross-linking pathway, since higher levels of
      pyridinoline cross-links were measured. Similar stimulatory effects on
      LH2b/COL1A2 mRNA expression and pyridinoline formation were observed for IL-4,
      activin A, and TNF-alpha. An exception was BMP-2, which has no effect on
      LH2b/COL1A2 mRNA levels nor on pyridinoline formation. Our data show for the
      first time that two processes, i.e., up-regulation of LH2b mRNA levels and
      increased formation of pyridinoline cross-links, previously recognized to be
      inherent to fibrotic processes, are induced by various profibrotic cytokines.

PMID- 15955453
TI  - Chronic depletion of glutathione (GSH) and minimal modification of LDL in vivo:
      its prevention by glutathione mono ester (GME) therapy.
AB  - A decline in reduced glutathione (GSH) level is associated with aging and free
      radical mediated diseases. The objective of this study was to determine whether
      the chronic depletion of extra cellular GSH causes oxidative damage to the
      circulating macromolecules such as lipoproteins. Decreased concentrations of
      plasma glutathione, vitamin E and ascorbic acid were recorded in the rats treated
      with buthionine sulfoximine (BSO), a selective GSH inhibitor. In LDL isolated
      from BSO-treated animals, the concentration of malondialdehyde (MDA) and
      conjugated dienes were significantly increased (P<0.01), whereas the levels of
      vitamin E were decreased (P<0.01). The analysis of total and LDL cholesterol
      revealed significant changes between the control and experimental groups. Of
      interest, altered concentrations of lyso-phosphatidyl choline (Lyso-PC) and
      phosphatidyl choline (PC) were recorded from the BSO mediated minimally modified
      LDL. A negative correlation between LDL-BDC/MDA and its antioxidant capacity was
      noted. Upon in vitro oxidation with CuSO(4), the electrophoretic behavior of
      purified LDL-apoprotein-B on agarose gel showed an increased mobility in BSO
      treated rats, indicative of in vivo modification of LDL to become susceptible for
      in vitro oxidation. The increased mobility of LDL (after in vitro oxidation)
      isolated from the BSO-treated animals correlates with a decrease in its amino
      groups, as determined by the trinitrobenzene sulfonic acid (TNBS) reactants.
      However, the mobility of LDL molecule was not altered due to BSO treatment in
      vivo. Interestingly, the minimal modification on LDL does not lead to any
      vascular damage in the dorsal aorta of the rats injected with BSO. The
      administration of glutathione monoester (GME), at a dose of 5 mmol/kg body
      weight, twice a day, for 30 days, to animals treated with l-buthionine-SR
      sulfoximine (BSO, 4 mmol/kg body weight, twice a day, for 30 days) normalized the
      antioxidant status and prevented the minimal modifications on LDL. Thus,
      increasing the cellular GSH levels may trigger beneficial effects against
      oxidative stress.

PMID- 15955455
TI  - Carnosine protects against the inactivation of esterase induced by glycation and
      a steroid.
AB  - Carnosine, an endogenous histidine-containing dipeptide, protects protein from
      oxidation and glycation, which may contribute to a potential treatment for some
      conformational diseases including cataract. Glycation, the non-enzymic reaction
      of sugars with proteins, promotes cross-linking and further aggregation.
      Prolonged use of glucocorticoids is a risk factor for cataract, as is diabetes.
      Esterase activity in the lens is decreased in senile cataract and diabetes.
      Previously, we reported that glycation and a steroid inactivate esterase. Here we
      tested the inactivation of esterase with fructose, fructose 6-phosphate (F6P) and
      ribose as model glycation reactions and prednisolone-21-hemisuccinate (P-21-H) as
      a model steroid and investigated the ability of carnosine to protect esterase
      against inactivation. The activity of esterase was measured by a
      spectrophotometric assay using p-nitrophenyl acetate as the substrate. The
      modified esterase was examined electrophoretically. The esterase was
      progressively inactivated by F6P, fructose, ribose and P-21-H. P-21-H was more
      effective than the sugars. Carnosine significantly inhibited the inactivation of
      esterase induced by all four compounds. Carnosine decreased the extent of the
      cross-linking. These results provide further evidence for carnosine's role as an
      anti-glycation compound. It is also proposed that carnosine may be an anti
      steroid agent.

PMID- 15955454
TI  - Inhibition of T cell MAPKs (Erk 1/2, p38) with thermal injury is related to down
      regulation of Ca2+ signaling.
AB  - We evaluated MAPK (Erk 1/2 and p38) signaling mechanisms of altered T-cell
      mediated immune responses in thermal injury condition. Rats were subjected to 30%
      body surface scald burn, and their mesenteric lymph node (MLN) and Peyer's patch
      (PP) T cells were purified using nylon wool method. Activation of MAPKs, Erk 1/2
      and p38 was assessed in T cells by determining its phosphorylation using
      immunoblot analysis, intracellular immunostaining and confocal microscopy. The
      results showed a down-regulation of Erk 1/2 and p38 activation in anti-CD3
      stimulated T cells from thermally injured animals, compared to Erk 1/2 and p38 in
      sham rat T cells. The down-regulation of MAPKs in T cells was reversed by
      treatment of T cells with calcium agonist, ionomycin. These data indicate that
      attenuated MAPKs (Erk 1/2, p38) activation in thermally injured animals' T cells
      could result from derangement of Ca(2+) mobilization. This finding suggests that
      T cell signaling derangements with thermal injury involve an altered cross-talk
      between Ca(2+) mobilization and MAPK signaling mechanisms.

PMID- 15955456
TI  - Bigendothelin-1 via p38-MAPK-dependent mechanism regulates adult rat ventricular
      myocyte contractility in sepsis.
AB  - We tested the hypothesis that exogenous administration of the ET-1 precursor,
      bigET-1, would regulate adult rat ventricular myocyte (ARVM) contractility in a
      p38-mitogen activated protein kinase (p38-MAPK)-dependent mechanism during
      sepsis. Ventricular myocytes from adult rat hearts (both sham and septic) were
      stimulated to contract at 0.5 Hz and mechanical properties were evaluated using
      an IonOptix Myocam system. Immunoblot analysis was used to determine the
      phosphorylation of p38-MAPK and extracellular signal-regulated kinase 1/2
      (ERK1/2). ARVMs were treated with vehicle, bigET-1 and inhibitors for 24 h and
      then subjected to functional and biochemical estimations. Septic ARVM displayed a
      distorted cell membrane and irregular network within the cells along with
      increased cell contractility as evidenced by elevated peak shortening (PS),
      maximal velocity of shortening (+dL/dt) and relengthening (-dL/dt) in comparison
      to sham ARVM. BigET-1 treatment caused ARVM enlargement in both sham and sepsis
      groups. BigET-1 (100 nM) produced an increase in ARVM contractility in sham group
      as compared to vehicle treatment. However, septic ARVM treated with bigET-1
      exhibited unaltered ARVM contractility, and upregulated ET(B) receptors as
      compared to respective sham group. BigET-1 increased the concentration of ET-1
      and upregulated phosphorylation of p38-MAPK but not of ERK1/2 in sham and septic
      ARVM. Furthermore, inhibition of p38-MAPK by SB203580 (10 microM) increased ARVM
      contractility in sham but not in sepsis group. BigET-1 reversed SB203580-induced
      increase in PS in sham group but accentuated it in sepsis group. BigET-1 also
      reversed SB203580-induced inhibition of p38-MAPK phosphorylation in sham but not
      in septic ARVM. SB203580 pretreatment followed by bigET-1 administration
      significantly decreased p38-MAPK phosphorylation and downregulated ET(B) receptor
      expression as compared to bigET-1 treatment per se in sepsis group but not in
      sham. We concluded that a bigET-1-induced non-responsive effect on septic ARVM
      contractile function could be due to upregulation of p38-MAPK phosphorylation and
      ET(B) receptor expression.

PMID- 15955457
TI  - Protection against amyloid beta-peptide (1-42)-induced loss of phospholipid
      asymmetry in synaptosomal membranes by tricyclodecan-9-xanthogenate (D609) and
      ferulic acid ethyl ester: implications for Alzheimer's disease.
AB  - Amyloid-beta (1-42) [Abeta (1-42)] deposition in the brain is a hallmark of
      Alzheimer's disease (AD) and has been shown to induce apoptosis and disrupt
      cellular ion homeostasis. Abeta (1-42) induces membrane lipid peroxidation, and 4
      hydroxynonenal (HNE) and 2-propenal (acrolein) are the two reactive products of
      lipid peroxidation, which structurally modify proteins by covalent interaction
      and inhibit enzyme function. Phosphatidylserine (PS), an aminophospholipid, is
      sequestered in the inner leaflet of the plasma membrane in nonstimulated cells.
      An early signal of synaptosomal apoptosis is the loss of phospholipid asymmetry
      and the appearance of phosphatidylserine in the outer leaflet of the membrane.
      The ATP-requiring enzyme, flippase, maintains phospholipid asymmetry of PS. Here,
      we have investigated the inactivation of the transmembrane enzyme
      aminophospholipid-translocase (or flippase) by Abeta (1-42). Flippase activity
      depends on a critical cysteine residue, a putative site of covalent modification
      by the Abeta (1-42)-induced lipid peroxidation products, HNE or acrolein. The
      present study is aimed to investigate the protective effects of tricyclodecan-9
      xanthogenate (D609) and ferulic acid ethyl ester (FAEE) on Abeta (1-42) induced
      modulation in phospholipid asymmetry in the synaptosomal membranes. Pretreatment
      of synaptosomes with D609 and FAEE significantly protected Abeta (1-42)-induced
      loss of phospholipid asymmetry in synaptosomal membranes. Our results suggest
      that D609 and FAEE exert protective effects against Abeta (1-42) induced
      apoptosis. The increase in intracellular Ca(2+) might not be the sole cause for
      the loss of flippase activity. Rather, other mechanisms that could modulate the
      function of flippase might be important in the modulation of phospholipid
      asymmetry. The results of this study are discussed with relevance to neuronal
      loss in the AD brain.

PMID- 15955458
TI  - The finding of new genetic polymorphism of UCP-1 A-1766G and its effects on body
      fat accumulation.
AB  - A-1766G polymorphism, for the first time, has been found in the sequencing of
      pooled and individual genomic DNA of Korean subjects at the 5' flanking region of
      the UCP-1 gene. The effects of new polymorphism on body fat were elucidated among
      387 Korean female subjects. It was shown that the genotypes AA, AG, and GG were
      consisted of 57.4%, 37.7%, and 4.9%, respectively, which was in agreement with
      Hardy-Weinberg equilibrium (P=0.327). The frequency of major A allele was 0.762
      and that of minor G allele was 0.238. It is found that the waist-hip ratio (WHR)
      (P=0.008), body fat mass (P=0.023), and percent body fat (P=0.014) are
      significantly higher in the AG/GG type compared to the AA type. When the subjects
      were analyzed using computerized tomography, there were significant increases in
      the AG/GG type compared to the AA type in the abdominal subcutaneous fat
      (P=0.015) and the abdominal visceral fat (P=0.013), respectively. A-1766G is
      approximately 2 kb downstream from the well-known A-3826G polymorphism, and no
      linkage between them was found (D'=0.929, R(2)=0.283). Three haplotypes
      (frequency >0.05) were examined from two polymorphisms and studied for their
      physiological effects. It was found that haplotype [GG] was significantly
      associated with increased body fat, while haplotype [GA] was associated with
      decreased body fat.

PMID- 15955459
TI  - A combined defect in the biosynthesis of N- and O-glycans in patients with cutis
      laxa and neurological involvement: the biochemical characteristics.
AB  - Based on our preliminary observation of abnormal glycosylation in a cutis laxa
      patient, nine cutis laxa patients were analyzed for congenital defects of
      glycosylation (CDG). Isoelectric focusing of plasma transferrin and
      apolipoproteinC-III showed that three out of nine patients had a defect in the
      biosynthesis of N-glycans and core 1 mucin type O-glycans, respectively. Mass
      spectrometric N-glycan analyses revealed a relative increase of glycans lacking
      sialic acid and glycans lacking sialic acid and galactose residues. Mutation
      analysis of the fibulin-5 gene (FBLN5), which has been reported in cases of
      autosomal recessive cutis laxa, revealed no mutations in the patients' DNA.
      Evidence is presented that extracellular matrix (ECM) proteins of skin are likely
      to be highly glycosylated with N- and/or mucin type O-glycans by using algorithms
      for predicting glycosylation. The conclusions in this study were that the
      clinical phenotype of autosomal recessive cutis laxa seen in three patients is
      not caused by mutations in the FBLN5 gene. Our findings define a novel form of
      CDG with cutis laxa and neurological involvement due to a defect in the
      sialylation and/or galactosylation of N- and O-glycans. Improper glycosylation of
      ECM proteins of skin may form the pathophysiological basis for the cutis laxa
      phenotype.

PMID- 15955460
TI  - Oxidative modification of rat eye lens proteins by peroxyl radicals in vitro:
      protection by the chain-breaking antioxidants stobadine and Trolox.
AB  - In an attempt to model the processes of free radical-mediated cataractogenesis,
      we investigated the oxidative modification of rat eye lens proteins by peroxyl
      radicals generated by thermal decomposition of 2,2'-azobis(2
      amidinopropane)hydrochloride (AAPH) under aerobic conditions. When incubated with
      AAPH, the soluble eye lens proteins precipitated in a time-dependent manner. The
      insolubilisation was accompanied by the accumulation of protein free carbonyls
      and the diminution of sulfhydryls, yet the processes were shifted in time. The
      SDS-PAGE analysis of the AAPH-treated proteins revealed the presence of high
      molecular weight cross-links and, to a lesser extent, fragments. The aggregation
      and cross-linking of proteins along with the generation of free carbonyls was
      significantly inhibited by the chain-breaking antioxidants stobadine and Trolox.
      On the other hand, the AAPH-initiated sulfhydryl consumption was much less
      sensitive to the antioxidants studied. The results point to a complex mechanism
      of peroxyl-radical-mediated modification of eye lens proteins with implications
      for cataract development and they indicate a potentially protective role of
      antioxidants.

PMID- 15955461
TI  - Loss of ecto-5'nucleotidase from porcine endothelial cells after exposure to
      human blood: Implications for xenotransplantation.
AB  - The endothelial cell surface expression of ecto-5'-nucleotidase (E5'N, CD73) is
      thought to be essential for the extracellular formation of cytoprotective, anti
      thrombotic and immunosuppressive adenosine. Decreased E5'N activity may play a
      role in xenograft acute vascular rejection, preventing accommodation and
      tolerance mechanisms. We investigated the extent of changes in E5'N activity and
      other enzymes of purine metabolism in porcine hearts or endothelial cells when
      exposed to human blood or plasma and studied the role of humoral immunity in this
      context. Pig hearts, wild type (WT, n = 6) and transgenic (T, n = 5) for human
      decay accelerating factor (hDAF), were perfused ex vivo with fresh human blood
      for 4 h. Pig aortic endothelial cells (PAEC) were exposed for 3 h to autologous
      porcine plasma (PP), normal (NHP) or heat inactivated human plasma (HHP), with
      and without C1-inhibitor. Enzyme activities were measured in heart or endothelial
      cell homogenates with an HPLC based procedure. The baseline activity of E5'N in
      WT and T porcine hearts were 6.60 +/- 0.33 nmol/min/mg protein and 8.54 +/- 2.10
      nmol/min/mg protein respectively (P < 0.01). Ex vivo perfusion of pig hearts with
      fresh human blood for 4 h resulted in a decrease in E5'N activity to 4.01 +/-
      0.32 and 4.52 +/- 0.52 nmol/min/mg protein (P < 0.001) in WT and T hearts
      respectively, despite attenuation of hyperacute rejection in transgenic pigs. The
      initial PAEC activity of E5'N was 9.10 +/- 1.40 nmol/min/mg protein. Activity
      decreased to 6.76 +/- 0.57 and 4.58 +/- 0.47 nmol/min/mg protein (P < 0.01) after
      3 h exposure of HHP and NHP respectively (P < 0.05), whereas it remained
      unchanged at 9.62 +/- 0.88 nmol/min/mg protein when incubated with PP controls.
      C1-inhibitor partially preserved E5'N activity, similar to the effect of HHP.
      Adenosine deaminase, adenosine kinase and AMP deaminase (other enzymes of purine
      metabolism) showed a downward trend in activity, but none were statistically
      significant. We demonstrate a specific decrease in E5'N activity in pig hearts
      following exposure to human blood which impairs adenosine production resulting in
      a loss of a cytoprotective phenotype, contributing to xenograft rejection. This
      effect is triggered by human humoral immune responses, and complement contributes
      but does not fully mediate E5'N depletion.

PMID- 15955462
TI  - Herbal remedies in the management of diabetes: lessons learned from the study of
      ginseng.
AB  - The only example of an approved antidiabetic drug that was developed from a
      herbal source with a long history of use for diabetes is the biguanide Metformin
      from French lilac (Galega officinalis). Clinical data are beginning to emerge
      that support antidiabetic indications for several other herbs. This viewpoint
      discusses the state of the evidence for their clinical antidiabetic efficacy. One
      of the most studied herbs, ginseng (Panax spp.), is used as a model to illustrate
      the challenges associated with achieving reproducible clinical efficacy. It is
      concluded that the best evidence for clinical efficacy in diabetes remains for
      ginseng. But overall insufficient evidence exists to claim a diabetes indication
      for herbs. The experience with ginseng suggests that although reproducible
      efficacy may be achieved using an acute postprandial clinical screening model to
      select an efficacious ginseng batch, dose, and time of administration, there is a
      need to develop a basis for standardization that ties the composition of herbs to
      efficacy. In absence of such standardization, the use of herbs in diabetes must
      be approached cautiously.

PMID- 15955463
TI  - Effect of antiatherogenic L-aspartate and L-glutamate on serum lipoproteins
      cholesterol and apolipoproteins A-1 and B in rabbits fed with high cholesterol
      diet.
AB  - BACKGROUND AND AIM: It has been shown that aspartate and glutamate inhibit
      mononuclear cell adhesion to the endothelium and formation of foam cells in the
      intima of thoracic aorta in cholesterol-fed rabbits. The purpose of the present
      study was to investigate whether a high cholesterol diet supplemented with
      aspartate and glutamate may alter lipoproteins cholesterol and apolipoproteins A
      1 and B levels in rabbits. METHODS AND RESULTS: Serum total cholesterol (TC),
      high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol
      (LDL-C), triglycerides (TG), apolipoprotein A-1 (apoA-1), apolipoprotein B
      (apoB), atherogenic index (AI) and apoA-1/apoB ratio were determined in 17 male
      New Zealand white rabbits fed a cholesterol plus corn oil diet (control group) or
      the same diet supplemented with aspartate and glutamate (Asp+Glu group) for 4
      weeks. Both diets were found to increase TC, LDL-C, apoB and AI, while apoA
      1/apoB ratio was decreased compared to baseline values. TG did not seem to be
      affected in the 4 weeks time in both groups. There was a significant increase of
      HDL-C in Asp+Glu group and a marked decrease of apoA-1 in control group during
      the study. CONCLUSIONS: Oral administration of aspartate and glutamate has been
      shown to inhibit fatty streak initiation in cholesterol-fed rabbits. The two
      amino acids did not have any effect on serum TC, LDL-C, TG and apoB
      concentrations. However, they increased HDL-C and maintained apoA-1 levels. Their
      antiatherogenic effect probably may be explained by different mechanisms than
      these related to the atherogenic lipids lowering, and it is possible to involve
      HDL-C and apoA-1.

PMID- 15955464
TI  - Hypoxia/reoxygenation alters essential fatty acids metabolism in cultured rat
      cardiomyocytes: protection by antioxidants.
AB  - BACKGROUND AND AIMS: Peroxidation of membrane lipids, altering cell integrity and
      function, plays an important part in the onset and development of cardiac damage
      following ischemia and reperfusion. Cells maintain their membrane lipid
      homeostasis by substituting peroxidized lipids with new polyunsaturated fatty
      acids. The microsomal enzymatic system converting essential fatty acids to highly
      unsaturated fatty acids (HUFAs) contributes to this repairing mechanism. The
      membrane of the endoplasmic reticulum could be one of the potential targets of
      free radicals generated in ischemia/reperfusion, thus causing a reduced efficacy
      of the system required for HUFA biosynthesis. To verify this hypothesis, and the
      consequent modification in fatty acid composition, we exposed cultured rat
      cardiomyocytes to different periods of hypoxia (H), eventually followed by
      reoxygenation (R). Furthermore, the effectiveness of antioxidants like alpha
      tocopherol and a green tea extract in counteracting H/R damage towards HUFA
      biosynthesis was tested. METHODS AND RESULTS: Linoleic (LA) and alpha-linolenic
      acid (ALA) conversion was measured by pre-labelling cells with [1-14C]LA or [1
      14C]ALA for 1 h; total lipid fatty acid composition was determined by gas
      chromatographic analysis. H profoundly affected HUFA biosynthesis, and this
      effect was much more evident on LA than on ALA. Conversion of both substrates was
      partially restored during R due to the readmission of the final acceptor of the
      desaturating complex. Fatty acid composition data were in agreement with the
      modifications observed in essential fatty acid conversion. Antioxidant protection
      appeared to be related to the duration of H, and to be more effective during H
      than during R. CONCLUSION: This study points out the importance of possessing
      good antioxidant defenses not only after, but mainly prior to the onset of H.

PMID- 15955465
TI  - Effect of dietary supplementation with glucomannan on plasma total cholesterol
      and low density lipoprotein cholesterol in hypercholesterolemic children.
AB  - AIM: This paper evaluates the effect of the adjunct of the hydrosoluble fiber
      glucomannan to a Step-One-Diet in 40 plasma hypercholesterolemic children, during
      a randomized controlled trial, to reduce plasma cholesterol. METHODS: All the
      subjects recruited underwent an 8-week run in diet period; a Step-One-Diet was
      prescribed. After that, they were randomly allocated to one of two groups: Step
      One-Diet only (control), and Step-One-Diet plus glucomannan in gelatine capsules.
      After another 8 weeks of treatment, the results were compared within and between
      the two groups. RESULTS: Glucomannan treated group showed decreased values in
      plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) vs.
      control group after 8 weeks of treatment. The percentage decrease showed a
      statistically significant difference between sex groups. Decreases were observed
      in favor of female vs. male children in TC (24% vs. 9%) and LDL-C (30% vs. 9%).
      CONCLUSIONS: These results suggest that glucomannan may represent a rationale
      adjunct to diet therapy in primary prevention in high risk hypercholesterolemic
      children.

PMID- 15955466
TI  - Cardiovascular risk factors in overweight German children and adolescents:
      relation to gender, age and degree of overweight.
AB  - OBJECTIVE: So far in Europe, no large studies have been published on the
      frequencies of the cardiovascular risk factors hypertension and dyslipidaemia in
      overweight children. METHODS: Diagnosis of hypertension, decreased HDL
      cholesterol, increased triglycerides, total and LDL-cholesterol were documented
      for 1004 overweight children and adolescents (aged 4-8 years, 52% girls, BMI-SDS
      in median 2.43) referred to four obesity centres. Hypertension and dyslipidaemia
      were defined by cut off points above the 95th percentile of healthy children.
      Multivariate linear regression was conducted for the dependent variables systolic
      and diastolic blood pressure, triglycerides, HDL-, LDL-, and total cholesterol,
      including gender, degree of overweight (SDS-BMI) and age as independent
      variables. RESULTS: Thirty-seven percent of the children studied suffered from
      hypertension, 27% displayed increased total cholesterol, 26% increased LDL
      cholesterol, 20% increased triglycerides and 18% decreased HDL-cholesterol.
      Seventy percent of all children had at least one unfavourable cardiovascular risk
      factor. Hypertension and dyslipidaemia were observed in any age group and in any
      degree of overweight at least twofold above the suspected rate of 5%. SDS-BMI was
      significantly related to blood pressure (systolic: coefficient 7.26, p < 0.001,
      diastolic: coefficient 3.21, p < 0.001), weakly to triglycerides (coefficient
      0.12, p = 0.007), slightly negatively to HDL-cholesterol (coefficient -0.06, p =
      0.001) and not related to total and LDL-cholesterol. Age was positively related
      to blood pressure (systolic: coefficient 2.436, p < 0.001, diastolic: coefficient
      0.54, p < 0.001) and negatively to HDL cholesterol (coefficient -0.02, p <
      0.001). CONCLUSION: Cardiovascular risk factors were frequently present in a
      large collective of overweight European children and adolescents. They occurred
      mostly independently of age, gender and degree of overweight. Therefore,
      screening for cardiovascular risk factors seems meaningful at any age and degree
      of overweight in childhood.

PMID- 15955467
TI  - Dietary and serum vitamins and minerals as predictors of myocardial infarction
      and stroke in elderly subjects.
AB  - BACKGROUND AND AIM: According to a widespread hypothesis, antioxidative vitamins
      and trace elements may protect the body against atherosclerotic diseases,
      especially in the elderly. We assessed dietary and serum vitamins and minerals
      for prediction of acute myocardial infarction (AMI) and stroke in elderly
      subjects. METHODS AND RESULTS: In a population-based health survey with special
      emphasis on the diet, subjects aged 65-99 years were followed up for up to 10
      years. The study population consisted of 361 men and 394 women. Information on
      individual food consumption was elicited by means of dietary history interviews.
      Serum vitamins and mineral elements were analysed utilizing commonly applied
      biochemical methods. Prediction analyses were based on 130 cases accumulated in
      the AMI group, 70 subjects in the stroke group, and corresponding control
      subjects. The cases were determined on the basis of revised information from the
      National Register of Cases of Death, and from the National Hospital Discharge
      Register. Low intake of vitamin D (p = 0.011) and low serum levels of 1,25
      dihydroxy-vitamin D (p = 0.0053) were significantly predictive of stroke when
      adjusted for age, gender, smoking and functional capacity. On the other hand,
      high dietary intakes of two flavonoids, luteolin (p = 0.0096) and kaempferol (p =
      0.002) were associated with lowered risk of AMI. Furthermore, low serum levels of
      iron predicted both AMI (p = 0.013) and stroke (p = 0.019). The results remained
      essentially unchanged when adjusted for additional major risk factors of
      atherosclerosis. CONCLUSIONS: From the items in the dietary interview, low
      intakes of vitamin D and certain flavonoids emerged as the sole predictors of AMI
      and stroke. In biochemical analyses, on the other hand, these disorders were
      predicted only by low levels of 1,25-dihydroxy-vitamin D and iron in the serum.

PMID- 15955468
TI  - Laparoscopic gastric banding and body composition in morbid obesity.
AB  - BACKGROUND AND AIM: Gastric banding induced considerable and rapid weight loss in
      morbid obesity. Nevertheless data on changes in body composition following
      gastric banding are scanty. In this study, we evaluated the 2-year changes in
      body composition in a small group of morbidly obese women treated by laparoscopic
      adjustable gastric banding (LAGB) associated with a well balanced low-calorie
      diet. METHODS AND RESULTS: We studied 20 premenopausal morbid obese women with
      BMI ranging from 35 to 57 (kg/m2) before, and 6, 12 and 24 months after
      laparoscopic adjustable gastric banding (LAGB). A well balanced 5.4 MJ/day
      hypocaloric diet was prescribed after surgery. Total body water (TBW), fat-free
      mass (FFM) and fat mass (FM) were investigated using conventional bioelectrical
      impedance analysis (BIA). Tissue hydration was also assessed by impedance vector
      analysis and the RXc graph method. The subjects showed a total weight loss of 28%
      of baseline body weight. In the first 6 months after surgery, patients lost
      18.5+/-5.9 kg of body weight (17.6+/-6.2 kg of FM and 0.7+/-1.4 kg of FFM). From
      6 to 12 months, a further 12.5+/-7.5 kg of body weight was lost (10.5+/-8.2 kg of
      FM and 2.2+/-3.8 kg of FFM). During the last 12 months, weight loss was 3.0+/-2.3
      kg (1.9+/-3.7 kg of FM and 1.1+/-2.9 kg of FFM). The weight loss observed after
      LAGB was mainly due to a decrease in FM, whereas TBW, FFM and BCM were only
      slightly and non-significantly reduced. No changes in body hydration status were
      observed after surgery. CONCLUSIONS: LAGB associated with a well balanced low
      calorie diet achieved a satisfactory 2-year weight loss, while sparing FFM and
      not causing body fluid alterations.

PMID- 15955470
TI  - Effects of subtotal fasting on plasmatic coagulation, fibrinolytic status and
      platelet activation: a controlled pilot study in healthy subjects.
AB  - BACKGROUND AND AIM: There is considerable controversy as to whether fasting can
      be recommended to patients with cardiovascular disease. The objective of this
      study was to determine whether a well-known method of 1-week subtotal fasting
      affects hemostasis in healthy subjects. METHODS AND RESULTS: Analyses were
      carried out before, four times during and 3 days after fasting in 12 fasting
      subjects (< 300 kcal/day, only from carbohydrates) (group 1), and 8 control
      subjects (group 2). Plasmatic coagulation (prothrombin time, partial
      thromboplastin time, p < or = 0.001) and fibrinolysis (plasminogen, plasmin
      antiplasmin-complex, p < 0.05) increased during fasting but remained within the
      normal limits. While the platelet count was similar in both groups, platelet
      sensitivity to stimulators was reduced in group 1 (P-selectin and activated GP
      IIb/IIIa on ADP-stimulated platelets, p < or = 0.01). Furthermore, soluble P
      selectin (p < or = 0.01) and C-reactive protein were decreased in comparison to
      group 2 (p < or = 0.05). CONCLUSIONS: Hemostasis and inflammation parameters
      during 1-week subtotal fasting do not imply an increase in cardiovascular risk.

PMID- 15955469
TI  - Cardiovascular risk factors and metabolic control in type 2 diabetic subjects
      attending outpatient clinics in Italy: the SFIDA (survey of risk factors in
      Italian diabetic subjects by AMD) study.
AB  - BACKGROUND AND AIM: To perform an observational, cross-sectional study aiming to
      assess multiple cardiovascular risk factors and metabolic control in a very large
      and representative sample of type 2 diabetic subjects attending diabetes
      outpatient clinics (DOCs) in Italy. METHODS AND RESULTS: Two hundred and sixty
      one clinics were involved, representing about one-third of the whole number of
      DOCs in the Country. Each clinic recruited on a random basis from 50 to 100 type
      2 diabetic patients aged 35-70 years, diagnosed more than six months before the
      start of the study. Demographic and clinical data were collected and blood
      pressure, lipids, HbA(1c), fasting blood glucose (FBG), and microalbuminuria were
      measured. Overall, 12,222 type 2 diabetic patients were recruited in 253 DOCs.
      Female subjects showed higher FBG, HbA 1c, blood pressure, lipid levels, and a
      longer duration of disease. The proportion of patients with BMI > or = 30 was
      33.3% among males and 45.9% among females; 40.9% of male patients had a waist
      circumference greater than 102 cm, while 79% of female patients had a waist
      circumference over 88 cm. More than two-third of the patients (74.4%) had
      systolic blood pressure values of > or = 130 mmHg, and one-third (33.2%) had
      diastolic values > or = 85 mmHg. The mean value of HbA(1c) was 7.6+/-1.6, and
      23.7% of the observed population had an HbA 1c level > 8.5%. More than half of
      the study population had total cholesterol levels > or = 5.2 mmol/l, 47% had LDL
      cholesterol values of 3.3 mmol/l or greater and 9.6% had HDL cholesterol level
      lower than 0.90 mmol/l. The presence of multiple lipid alterations was associated
      with markedly higher HbA 1c levels, in both subjects treated with lipid lowering
      drugs and untreated subjects. Finally, even moderate increases in HbA 1c levels
      (i.e. HbA 1c > 7.5%) were associated with a statistically significant greater
      risk of systolic blood pressure levels > or = 160 mmHg in women (OR = 1.40; 95%
      CI 1.09-1.80) but not in men (OR = 1.21; 95% CI 0.96-1.54). CONCLUSIONS: The
      SFIDA study provides a clear indication of the need to orient diabetes care
      towards the control of global cardiovascular risk. Only a stricter adherence to
      the existing guidelines and a much stronger attention to the attainment of the
      desired therapeutic goals will allow a decrease in morbidity and mortality as
      well as in the costs related to diabetes.

PMID- 15955471
TI  - Gene polymorphisms affecting HDL-cholesterol levels in the normolipidemic
      population.
AB  - BACKGROUND AND AIM: HDL-cholesterol (HDL-C) is inversely related to the risk of
      ischemic heart disease. Many genes are reported to affect HDL-C serum levels in
      both hyperlipidemic and normolipidemic populations, though the data are
      controversial. We examined the effect of common gene polymorphisms known to
      interfere with HDL-C metabolism (apolipoprotein E, cholesterol ester transfer
      protein and apolipoprotein A-IV gene polymorphisms) on HDL-C plasma levels in
      normolipidemic subjects. METHODS AND RESULTS: The study population consisted of
      200 normolipidemic individuals visiting our clinic for a routine check-up. None
      of the above gene polymorphisms affected HDL-C levels in our population. However,
      participants carrying the allele E4 of the apolipoprotein (apo) E gene, the
      allele B1 of the TaqIB polymorphisms in the cholesterol ester transfer protein
      (CETP) gene and the allele T of the apoA-IV gene (A to T polymorphism at site
      347) (n = 28) had statistically significantly lower HDL-C levels compared to
      those not carrying the above allele combination (0.99+/-0.33 vs 1.28+/-0.35
      mmol/L, p = 0.04). CONCLUSION: In this study, we describe a subgroup of
      normolipidemic individuals with low HDL-C levels due to genetic variability, and
      we discuss the underlying possible mechanisms involved.

PMID- 15955472
TI  - Gene-diet interaction in relation to the prevention of obesity and type 2
      diabetes: evidence from the Finnish Diabetes Prevention Study.
AB  - Both genetic and environmental factors are involved in the pathogenesis of
      obesity and type 2 diabetes. Most of the genetic studies on common obesity are
      confined to the links between a given gene polymorphism or gene loci and
      different phenotypes of obesity or anthropometric measures. Some studies indicate
      that genetic factors modify the weight reduction response to energy restriction
      or weight gain in the long-term. Only a few studies have focused on gene-diet
      interaction in the development of type 2 diabetes. The Finnish Diabetes
      Prevention Study shows (DPS) that the success of a lifestyle intervention depends
      also on the polymorphisms of those genes, which are suggested to play a role in
      energy metabolism, lipid metabolism, insulin resistance or insulin secretion.
      This review deals with selected genes examined so far in the DPS.

PMID- 15955473
TI  - Evaluation of alpha-tocopherol contained in plasma lipoproteins: How should the
      data be expressed?

PMID- 15955474
TI  - Diabetes prevention strategy in offspring of type 2 diabetic patients with a
      direct involvement of the diseased parents.

PMID- 15955475
TI  - A systematic investigation of the functional neuroanatomy of auditory and visual
      phonological processing.
AB  - Neuroimaging studies of auditory and visual phonological processing have revealed
      activation of the left inferior and middle frontal gyri. However, because of task
      differences in these studies (e.g., consonant discrimination versus rhyming), the
      extent to which this frontal activity is due to modality-specific linguistic
      processes or to more general task demands involved in the comparison and storage
      of stimuli remains unclear. An fMRI experiment investigated the functional
      neuroanatomical basis of phonological processing in discrimination and rhyming
      tasks across auditory and visual modalities. Participants made either
      "same/different" judgments on the final consonant or rhyme judgments on
      auditorily or visually presented pairs of words and pseudowords. Control tasks
      included "same/different" judgments on pairs of single tones or false fonts and
      on the final member in pairs of sequences of tones or false fonts. Although some
      regions produced expected modality-specific activation (i.e., left superior
      temporal gyrus in auditory tasks, and right lingual gyrus in visual tasks),
      several regions were active across modalities and tasks, including posterior
      inferior frontal gyrus (BA 44). Greater articulatory recoding demands for
      processing of pseudowords resulted in increased activation for pseudowords
      relative to other conditions in this frontal region. Task-specific frontal
      activation was observed for auditory pseudoword final consonant discrimination,
      likely due to increased working memory demands of selection (ventrolateral
      prefrontal cortex) and monitoring (mid-dorsolateral prefrontal cortex). Thus, the
      current study provides a systematic comparison of phonological tasks across
      modalities, with patterns of activation corresponding to the cognitive demands of
      performing phonological judgments on spoken and written stimuli.

PMID- 15955476
TI  - Differential activation of pre-SMA and SMA proper during action observation:
      effects of instructions.
AB  - Many neurophysiological studies give evidence for a matching system between
      action observation and imitation. We used functional MRI to investigate the
      effects of different instructions for observing identical stimuli of whole-body
      gymnastics movements. The imitative-like observation mode asked normal human
      participants to observe the sequence containing repetitive parts and to
      subsequently imagine the observed movements in the first-person perspective. The
      evaluative observation mode asked the participants to carefully observe and judge
      movement accuracy and consistency in the repetitive sequence. We hypothesized
      that the supplementary motor area would be specifically involved in performing
      the observational tasks. Results indicate that the SMA proper is generally
      activated during observation of whole-body gymnastic movements and shows
      pronounced activation in imitative-like observation mode. Pre-SMA activity can be
      differentially modulated by instructions related to the observation task.

PMID- 15955477
TI  - Estimating intensity variance due to noise in registered images: applications to
      diffusion tensor MRI.
AB  - Image registration techniques which require image interpolation are widely used
      in neuroimaging research. We show that signal variance in interpolated images
      differs significantly from the signal variance of the original images in native
      space. We describe a simple approach to compute the signal variance in registered
      images based on the signal variance and covariance of the original images, the
      spatial transformations computed by the registration procedure, and the
      interpolation or approximation kernel chosen. The method is general and could
      handle various sources of signal variability, such as thermal noise and
      physiological noise, provided that their effects can be assessed in the original
      images. Our approach is applied to diffusion tensor (DT) MRI data, assuming only
      thermal noise as the source of variability in the data. We show that incorrect
      noise variance estimates in registered diffusion-weighted images can affect DT
      parameters, as well as indices of goodness of fit such as chi-square maps. In
      addition to DT-MRI, we believe that this methodology would be useful any time
      parameter extraction methods are applied to registered or interpolated data, such
      as in relaxometry and functional MRI studies.

PMID- 15955478
TI  - Intraoperative functional MRI: implementation and preliminary experience.
AB  - For a non-invasive identification of eloquent brain areas in neurosurgical
      procedures up to now only preoperative functional brain mapping techniques are
      available. These are based, e.g., on preoperative functional magnetic resonance
      imaging (fMRI) investigations in awake patients. The aim of this study was to
      investigate the feasibility to perform fMRI during neurosurgical procedures in
      anesthetized patients. For that purpose, a passive stimulation paradigm with
      peripheral nerve stimulation was applied. A 1.5-T MR scanner placed in a
      radiofrequency-shielded operating room with an adapted operating table was used
      for intraoperative fMRI. The fMRI data were analyzed during acquisition by an
      online statistical evaluation package installed on the MR scanner console. In
      addition, phase reversal of somatosensory evoked potentials was used for
      verification of intraoperative fMRI. In four anesthetized patients with lesions
      in the vicinity of the central region a total of 11 fMRI measurements were
      successfully acquired and analyzed online. Activation was found in the
      somatosensory cortex, which could be confirmed by intraoperative phase reversal
      for each measurement. Furthermore, statistical parametric mapping (SPM) was
      employed for an extensive offline data analysis. We did not observe any
      neurological deterioration or complications due to the stimulation technique.
      Intraoperative fMRI is technically feasible allowing a real-time identification
      of eloquent brain areas despite brain shift.

PMID- 15955479
TI  - Multiple components of lateral posterior parietal activation associated with
      cognitive set shifting.
AB  - Posterior parietal activation has commonly been observed in previous neuroimaging
      studies in association with flexible shifting of cognitive set. However, it is
      not clear whether the parietal activation reflects cognitive processes intrinsic
      to the shifting itself or other confounding factors such as spatial attention. To
      address this issue, the Wisconsin Card Sorting Task (WCST) was modified such that
      spatial components were eliminated from the sensory and motor aspects of the
      task. Moreover, a visual instruction of a next dimension was introduced to
      eliminate cognitive processes related to trial and error identification of a next
      rule, and a control null-instruction was also introduced to eliminate
      perceptual/oddball effects of the instruction cue. Localizer scans using a
      visually guided saccade task were also conducted to identify eye movement/spatial
      attention-related areas. Activity related to set shifting with trial and error
      was revealed in the lateral parts of the intraparietal regions, while activity
      related to eye movements/spatial attention was revealed in the medial parts of
      the intraparietal regions, confirming little spatial contribution to the modified
      WCST as indexed by the double dissociation. The lateral intraparietal activity
      was bilateral, but when the instructed shifting was contrasted with the null
      instructed shifting to purify the shift-related activity further, the left
      intraparietal activation was significantly greater than that in the right
      hemisphere. These results reveal the left hemisphere dominance of purified
      shifting-related activity in the lateral posterior parietal cortex that may
      cooperate with the lateral prefrontal cortex whose left hemisphere dominance has
      already been reported.

PMID- 15955480
TI  - Effects of language experience: neural commitment to language-specific auditory
      patterns.
AB  - Linguistic experience alters an individual's perception of speech. We here
      provide evidence of the effects of language experience at the neural level from
      two magnetoencephalography (MEG) studies that compare adult American and Japanese
      listeners' phonetic processing. The experimental stimuli were American English
      /ra/ and /la/ syllables, phonemic in English but not in Japanese. In Experiment
      1, the control stimuli were /ba/ and /wa/ syllables, phonemic in both languages;
      in Experiment 2, they were non-speech replicas of /ra/ and /la/. The behavioral
      and neuromagnetic results showed that Japanese listeners were less sensitive to
      the phonemic /r-l/ difference than American listeners. Furthermore, processing
      non-native speech sounds recruited significantly greater brain resources in both
      hemispheres and required a significantly longer period of brain activation in two
      regions, the superior temporal area and the inferior parietal area. The control
      stimuli showed no significant differences except that the duration effect in the
      superior temporal cortex also applied to the non-speech replicas. We argue that
      early exposure to a particular language produces a "neural commitment" to the
      acoustic properties of that language and that this neural commitment interferes
      with foreign language processing, making it less efficient.

PMID- 15955481
TI  - Functional MRI of galvanic vestibular stimulation with alternating currents at
      different frequencies.
AB  - Functional MRI was performed in 28 healthy volunteers to study the effects of
      galvanic vestibular stimulation with alternating currents (AC-GVS) of different
      frequencies on brain activation patterns. The aims of this study were (1) to
      identify specific areas within the vestibular cortical network that are involved
      in the processing of frequency-specific aspects by correlation analyses, (2) to
      determine the optimal frequency for stimulation of the vestibular system with
      respect to perception, and (3) to analyze whether different frequencies of AC-GVS
      are mediated in different cortical areas or different sites within the vestibular
      cortex. AC-GVS was performed using sinusoidal stimulation currents with an
      amplitude of +/-2.5 mA, and frequencies of 0.1 Hz, 0.3 Hz, 0.8 Hz, 1.0 Hz, 2.0
      Hz, and 5.0 Hz were applied. Regardless of the applied stimulation frequency, AC
      GVS elicited activations within a network of multisensory areas similar to those
      described in earlier studies using direct currents. No mapping of different
      stimulation frequencies to different cortical locations was observed. Additional
      activations of somatosensory cortex areas were observed during stimulation with 5
      Hz only. The strongest vestibular sensations were reported during stimulation
      with 1 Hz and 2 Hz. Correlation analyses between blood oxygenation level
      dependent (BOLD) signal changes and stimulation frequency revealed a positive
      dependency in areas of the supramarginal gyrus, posterolateral thalamus,
      cerebellar vermis, posterior insula, and in the hippocampal region/uncus. These
      regions represent areas involved in the processing of vestibular information for
      head and body orientation in space.

PMID- 15955482
TI  - Directing spatial attention in mental representations: Interactions between
      attentional orienting and working-memory load.
AB  - Orienting spatial attention to locations in the extrapersonal world has been
      intensively investigated during the past decades. Recently, it was demonstrated
      that it is also possible to shift attention to locations within mental
      representations held in working memory. This is an important issue, since the
      allocation of our attention is not only guided by external stimuli, but also by
      their internal representations and the expectations we build upon them. The
      present experiment used behavioural measures and event-related functional
      magnetic resonance imaging to investigate whether spatial orienting to mental
      representations can modulate the search and retrieval of information from working
      memory, and to identify the neural systems involved, respectively. Participants
      viewed an array of coloured crosses. Seconds after its disappearance, they were
      cued to locations in the array with valid or neutral cues. Subsequently, they
      decided whether a probe stimulus was presented in the array. The behavioural
      results indicated that orienting of spatial attention within working memory
      attenuates the well-known effect of decreasing performance when memory load is
      increased. So "internal" spatial orienting seems to highlight information or
      facilitate search within working memory, which leads to advantages in retrieval.
      Imaging enabled the separation of brain areas supporting spatial orienting
      functions from those sensitive to working-memory load. Orienting of spatial
      attention to the contents of working memory activated posterior parietal cortex
      bilaterally, the insula, and lateral and medial frontal cortices.

PMID- 15955483
TI  - In vivo and ex vivo MRI detection of localized and disseminated neural stem cell
      grafts in the mouse brain.
AB  - The application of stem cells as delivery vehicles opens up the opportunity for
      targeting therapeutic proteins to the damaged or degenerating central nervous
      system. Neural stem cell (NSC) lines have been shown to engraft, differentiate
      and correct certain central nervous system diseases. The present study was
      performed to test the ability of magnetic resonance imaging (MRI) in detecting
      transplanted NSCs under conditions of limited migration in the normal adult mouse
      brain versus widespread migration when the cells are transplanted neonatally. The
      C17.2 NSC line was labeled in vitro with superparamagnetic iron oxide (SPIO)
      particles and the labeled cells were implanted intracranially. Serial in vivo
      gradient echo MR imaging was performed using a 4.7 T horizontal bore magnet. High
      resolution ex vivo images of the isolated brains were performed at 9.4 T, and the
      presence of iron was correlated with Prussian blue staining in histological
      sections. Adult animals injected with SPIO-labeled stem cells exhibited
      hypointense regions near the injection site that were observed up to 32 days
      after injection. In neonatally transplanted animals, MR signal intensity from
      transplanted NSCs was not apparent in in vivo imaging but ex vivo MR images
      revealed small hypointense regions throughout the brain including the olfactory
      bulbs, cortex and the cerebellum, reflecting the wide distribution of the
      engrafted cells. These regions were correlated with Prussian blue staining, which
      confirmed the presence of SPIO particles inside the engrafted cells. We have
      shown that MRI is capable of differentiating localized and widespread engraftment
      of C17.2 stem cells in the central nervous system.

PMID- 15955484
TI  - Motor facilitation of the human cortico-spinal system during observation of bio
      mechanically impossible movements.
AB  - Neurophysiological and neuroimaging studies in the human and the monkey brain
      indicate that links between action observation and execution are much tighter
      than previously believed. Indeed, the mere observation of movements performed by
      other individuals brings about a clear increase in activity in specific fronto
      parietal neural networks (mirror system). Here, we report a series of four single
      pulse transcranial magnetic stimulation studies of the motor system, which show
      that observation of index and little finger movements brings about a facilitation
      of potentials recorded from muscles that would be involved in the actual
      execution of the observed action. Remarkably, however, a clear representational
      selectivity was found also during observation of bio-mechanically impossible
      index or little finger movements. Thus, in movement observation tasks, the human
      cortico-spinal system reacts similarly to the vision of bio-mechanically possible
      and impossible movements but it is able to detect which muscle would be involved
      in the actual execution of the observed movement. Importantly, this system may be
      more related to coding body part movements than precisely simulating their
      execution.

PMID- 15955485
TI  - Reproducibility of cortex-muscle coherence.
AB  - Cortex-muscle coherence is a frequency-analysis technique that has been
      increasingly applied in the investigation of movement disorders. To study the
      intra- and inter-session stability of the cortex-muscle coherence, we recorded
      from 12 healthy subjects magnetoencephalographic (MEG) and surface
      electromyographic (EMG) signals during unilateral isometric contractions of the
      left- and right-hand muscles. Two identical measurements were performed during
      one session, and the session was repeated once after about 1 year. In one
      experienced subject, the recordings were repeated seven times within 20 months.
      The MEG-EMG coherence exceeded the noise level in 10 out of 12 subjects. Both the
      frequency (correlation coefficient r = 0.77-0.93, P < 0.01) and strength (r =
      0.78-0.91, P < 0.01) of coherence were well reproducible within each session for
      both left- and right-sided contractions. The inter-session reproducibility was
      high for the mean of cumulative coherence frequency (r = 0.90-0.95, P < 0.01),
      but relatively low for coherence strength (r = 0.43-0.59, P > 0.05). The results
      for one subject participating in 8 repeated sessions strongly supported the
      results of the whole group. Thus, intra-session reproducibility of both strength
      and frequency of the cortex-muscle coherence is good and studies comparing
      different conditions at the group level within one session are feasible. However,
      caution is needed when interpreting absolute levels or changes in the strength of
      coherence in single subjects between the sessions.

PMID- 15955486
TI  - Fiber tracking by diffusion tensor imaging in corticospinal tract stroke:
      Topographical correlation with clinical symptoms.
AB  - Fiber tracking of the white matter using diffusion tensor imaging is a new
      imaging technique to visualize the integrity of the white matter. This study
      investigated the capability of this technique to localize the lacunar
      infarctions, particularly with respect to the body parts affected, by correlating
      the location of the lesion with the clinical symptoms topographically. Twenty
      seven patients with capsular and pericapsular small acute infarctions underwent
      diffusion tensor imaging and subsequent fiber tracking of the corticospinal tract
      (CST). According to the lesion topography with regard to the CST, the infarctions
      were classified into four types: (1) the anterior type (n = 9) involving the
      anterior part of the CST, (2) the central type (n = 9) involving the middle or
      whole part of the CST, (3) the posterior type (n = 5) involving the posterior
      part of the CST and (4) the intact type (n = 4) not involving the CST. Motor
      weakness of the face, upper extremities and lower extremities was found at 100%,
      67% and 44%, respectively in the anterior type, at 89%, 100% and 89%,
      respectively in the central type and at 20%, 80% and 100%, respectively in the
      posterior type. The intact type was not associated with motor weakness. In
      conclusion, the fiber tracking technique of the CST enables the specific
      localization of capsular and pericapsular infarctions with regard to the body
      parts affected. These results also confirm the topographical accuracy of the
      fiber tracking of the CST.

PMID- 15955487
TI  - Gray matter volume reduction in the chronic fatigue syndrome.
AB  - The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology.
      The symptomatology of CFS (central fatigue, impaired concentration, attention and
      memory) suggests that this disorder could be related to alterations at the level
      of the central nervous system. In this study, we have used an automated and
      unbiased morphometric technique to test whether CFS patients display structural
      cerebral abnormalities. We mapped structural cerebral morphology and volume in
      two cohorts of CFS patients (in total 28 patients) and healthy controls (in total
      28 controls) from high-resolution structural magnetic resonance images, using
      voxel-based morphometry. Additionally, we recorded physical activity levels to
      explore the relation between severity of CFS symptoms and cerebral abnormalities.
      We observed significant reductions in global gray matter volume in both cohorts
      of CFS patients, as compared to matched control participants. Moreover, the
      decline in gray matter volume was linked to the reduction in physical activity, a
      core aspect of CFS. These findings suggest that the central nervous system plays
      a key role in the pathophysiology of CFS and point to a new objective and
      quantitative tool for clinical diagnosis of this disabling disorder.

PMID- 15955489
TI  - Oscillatory motor cortex-muscle coupling during painful laser and nonpainful
      tactile stimulation.
AB  - Noxious stimulation activates-in addition to the brain structures related to
      sensory, emotional, and cognitive components of pain-also the brain's motor
      system. Effect of noxious input on the primary motor (MI) cortex remains,
      however, poorly understood. To characterize this effect in more detail, we
      quantified the ongoing oscillatory communication between the MI cortex and hand
      muscles during selectively noxious laser stimulation. The subjects maintained an
      isometric contraction of finger muscles while receiving the laser stimuli to the
      dorsum of the hand. Tactile stimuli with well-known effects on the MI cortex
      reactivity served as control stimuli. Cortex-muscle coherence was computed
      between magnetoencephalographic (MEG) signals from the contralateral MI and
      electromyographic (EMG) signals from the hand muscles. Statistically significant
      coherence at approximately 20 Hz was found in 6 out of 7 subjects. The coherence
      increased phasically after both types of stimuli but significantly later after
      laser than tactile stimuli (mean +/- SEM peak latencies 1.05 +/- 0.12 s vs. 0.58
      +/- 0.06 s; P < 0.05), and the coherence increase lasted longer after laser than
      tactile stimuli (0.87 +/- 0.09 s vs. 0.50 +/- 0.06 s, P < 0.05). The observed
      coherence increase could be related to stabilization of the motor-cortex control
      after sensory input. Our findings add to the clinically interesting evidence
      about the cortical pain-motor system interaction.

PMID- 15955490
TI  - Cerebellum and M1 interaction during early learning of timed motor sequences.
AB  - We used positron emission tomography (PET) to examine within-day learning of
      timed motor sequences. The results of this experiment are novel in showing an
      interaction between cerebellum and primary motor cortex (M1) during learning that
      appears to be mediated by the dentate nucleus (DN) and in demonstrating that
      activity in these regions is directly related to performance. Subjects were
      scanned during learning (LRN) across three blocks of practice and during
      isochronous (ISO) and perceptual (PER) baseline conditions. CBF was compared
      across blocks of learning and between the LRN and baseline conditions. Results
      demonstrated an interaction between the cerebellum and M1 such that earlier,
      poorer performance was associated with greater activity in the cerebellar
      hemispheres and later, better performance was associated with greater activity in
      M1. Inter-regional correlation analyses confirmed that as CBF in the cerebellum
      decreases, blood flow in M1 increases. Importantly, these analyses also revealed
      that activity in cerebellar cortex was positively correlated with activity in
      right DN and that DN activity was negatively correlated with blood flow in M1.
      Activity in the cerebellar hemispheres early in learning is likely related to
      error correction mechanisms which optimize movement kinematics resulting in
      improved performance. Concurrent DN activity may be related to encoding of this
      information and DN output to M1 may play a role in consolidation processes that
      lay down motor memories. Increased activity in M1 later in learning may reflect
      strengthening of synaptic connections associated with changes in motor maps that
      are characteristic of learning in both animals and humans.

PMID- 15955488
TI  - Hemispheric differences in hemodynamics elicited by auditory oddball stimuli.
AB  - Evidence from neuroimaging studies suggests that the right hemisphere of the
      human brain might be more specialized for attention than the left hemisphere.
      However, differences between right and left hemisphere in the magnitude of
      hemodynamic activity (i.e., 'functional asymmetry') rarely have been explicitly
      examined in previous neuroimaging studies of attention. This study used a new
      voxel-based comparison method to examine hemispheric differences in the amplitude
      of the hemodynamic response in response to infrequent target, infrequent novel,
      and frequent standard stimuli during an event-related fMRI auditory oddball task
      in 100 healthy adult participants. Processing of low probability task-relevant
      target stimuli, or 'oddballs', and low probability task-irrelevant novel stimuli
      is believed to engage in orienting and attentional processes. It was hypothesized
      that greater right-hemisphere activation compared to left would be observed to
      infrequent target and novel stimuli. Consistent with predictions, greater right
      hemisphere than left frontal, temporal, and parietal lobe activity was observed
      for target detection and novelty processing. Moreover, asymmetry effects did not
      differ with respect to age or gender of the participants. The results (1) support
      the proposal that the right hemisphere is differentially engaged in processing
      salient stimuli and (2) demonstrate the successful use of a new voxel-based
      laterality analysis technique for fMRI data.

PMID- 15955491
TI  - Parahippocampal activation evoked by masked traumatic images in posttraumatic
      stress disorder: a functional MRI study.
AB  - Posttraumatic stress disorder (PTSD) has been widely studied, but its neural
      mechanism is still unclear. The purpose of this study is to identify
      dysfunctional areas in PTSD throughout the whole brain to help to elucidate the
      neural mechanisms of PTSD. Sixteen patients with PTSD and sixteen healthy
      controls participated in this study. Traumatic images under perceptual threshold
      including scenes of earthquakes, traffic accidents, ambulances, emergency rooms,
      and crimes were presented to the participants, and brain activation was measured
      using functional MRI. Functional brain images of both groups were evaluated with
      random effect analysis for the whole brain. In the control group, activation in
      the ventral frontoparietal areas correlated significantly with presentation of
      the masked traumatic stimuli. In the PTSD group, activation was not observed in
      these areas, but significant activation correlated with the masked traumatic
      stimuli in the parahippocampal region including the left parahippocampal gyrus
      and tail of the left hippocampus. These results suggest that in PTSD patients
      activation in the ventral frontoparietal network associated with visual attention
      processing is attenuated, while the left hippocampal area associated with
      episodic and autobiographical memory is abnormally easily activated. This pattern
      of activation corresponds well to the clinical characteristics of PTSD, in which
      even slight traumatic stimuli tend to induce intrusive recollection or
      flashbacks, despite a general decrease in attention and ability to concentrate.

PMID- 15955492
TI  - Mean diffusivity and fractional anisotropy histogram analysis of the cervical
      cord in MS patients.
AB  - The spinal cord is frequently involved in multiple sclerosis (MS), and cord
      damage may be an important contributor to disability. Diffusion tensor magnetic
      resonance imaging (DT-MRI) provides quantitative information about the structural
      and orientational features of the central nervous system. In order to assess
      whether diffusion tensor-derived measures of cord tissue damage are related to
      clinical disability, mean diffusivity (MD) and fractional anisotropy (FA)
      histograms from the cervical cord were acquired from a large cohort of MS
      patients. Diffusion-weighted sensitivity-encoded (SENSE) echo planar images of
      the cervical cord, and brain dual-echo and diffusion-weighted scans were acquired
      from 44 patients with MS and 17 healthy controls. Cord and brain MD and FA
      histograms were produced. An analysis of variance model, adjusting for cord
      volume and patient age, was used to compare cord DT-MRI parameters from controls
      and patients. A multivariate linear regression model was used to identify DT-MRI
      variables independently associated with disability. Average cervical cord FA was
      significantly lower in MS patients compared to controls. Cord cross-sectional
      area, average FA and average MD were all significantly correlated with the degree
      of disability (r values ranging from 0.36 to 0.51). The multivariate linear
      regression model retained average cord FA and average brain MD as variables
      independently associated with disability, with a correlation coefficient of 0.73
      (P < 0.001). DT-MRI reveals a loss of cervical cord tissue structure in MS
      patients. The strong correlation found between a composite DT-MRI score and
      disability suggests that a full and accurate assessment of cervical cord damage
      in MS provides information that usefully contributes to an explanation of the
      clinical manifestations of the disease.

PMID- 15955493
TI  - Emotional context during encoding of neutral items modulates brain activation not
      only during encoding but also during recognition.
AB  - In general, encoding of neutral material includes the context in which the
      respective material is learned. The effect of emotional context on successfully
      encoded neutral material has been investigated only recently in few studies, but
      the main underlying mechanisms are still fairly unknown. In the present study, we
      investigated the effect of positive and negative emotional context on encoding
      and later recognition of neutral items. We could demonstrate that brain
      activation not only during encoding but also during recognition of neutral items
      depended on the emotional valence of the encoding context. Whereas activation of
      medial temporal lobe structures during encoding specifically predicted subsequent
      memory when learning appears in a positive emotional context, activation of the
      anterior temporal cortex in a region with afferent input to the amygdala
      predicted memory for material learned in negative context. Recognition of items
      encoded in positive emotional context revealed activation of hippocampal and
      medial prefrontal regions, recognition of items encoded in negative emotional
      context revealed activation of the caudate nucleus. We assume that our findings
      reflect the recruitment of different brain circuits depending on the emotional
      context during learning.

PMID- 15955494
TI  - Unified segmentation.
AB  - A probabilistic framework is presented that enables image registration, tissue
      classification, and bias correction to be combined within the same generative
      model. A derivation of a log-likelihood objective function for the unified model
      is provided. The model is based on a mixture of Gaussians and is extended to
      incorporate a smooth intensity variation and nonlinear registration with tissue
      probability maps. A strategy for optimising the model parameters is described,
      along with the requisite partial derivatives of the objective function.

PMID- 15955495
TI  - Comparison of fMRI activation as measured with gradient- and spin-echo EPI during
      visual perception.
AB  - In this study, we compared fMRI activation measured with gradient- and spin-echo
      based fMRI during visual perception of faces, which is mediated by neural
      activation within a distributed cortical network. With both fMRI techniques,
      bilateral activation was observed in multiple regions including the inferior
      occipital gyrus, fusiform gyrus, superior temporal sulcus, amygdala, inferior
      frontal gyrus, and orbitofrontal cortex. When compared with the gradient-echo
      sequence, activation measured with the spin-echo sequence was significantly
      reduced. This decrease was manifested by smaller cluster size, lower statistical
      significance, smaller amplitude of the fMRI signal, and smaller number of
      subjects who showed activation in all face-responsive regions. In orbitofrontal
      cortex, a region prone to susceptibility-related signal dephasing, the spin-echo
      acquisition considerably restored the signal, but did not reveal stronger
      activation when compared with the gradient-echo acquisition. Our data indicate
      that optimized GE sequences that reduce susceptibility artefacts are sufficient
      to detect activation in regions such as the orbitofrontal cortex.

PMID- 15955496
TI  - Cognitive control and brain resources in major depression: an fMRI study using
      the n-back task.
AB  - Several neuroimaging studies have reported 'hypofrontality' in depressed patients
      performing a cognitive challenge compared to control subjects. Hypofrontality in
      depression is likely associated with an impaired behavioral performance. It is
      unclear whether this impaired performance is the consequence or the cause of
      hypofrontality. Consequently, we proposed to compare the cerebral activity of
      depressed patients and healthy subjects while controlling for the level of
      performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10
      healthy controls were tested with a verbal version of the n-back task during fMRI
      scanning. The working memory load was manipulated across the experiment (1,2,3
      back) to increase the cognitive demands. fMRI data were acquired on a 1.5-T GE
      scanner and analyzed using SPM99 software. We did not find any difference between
      groups in both performance and reaction times for each level of complexity of the
      n-back task. Depressed patients and control subjects showed bilateral activation
      of the lateral prefrontal cortex, anterior cingulate and parietal cortex.
      Activation of these regions was modulated by the complexity of the task. Within
      this n-back neural network, depressed patients showed greater activation of the
      lateral prefrontal cortex and the anterior cingulate compared to healthy
      subjects. This study provides evidence that depressed patients need greater
      activation within the same neural network to maintain a similar level of
      performance as controls during a working memory task. Our findings suggest that
      depression may impair the cognitive capacity of depressed patients by recruiting
      more brain resources than controls during cognitive control.

PMID- 15955497
TI  - Bayesian analysis of the neuromagnetic inverse problem with l(p)-norm priors.
AB  - Magnetoencephalography (MEG) allows millisecond-scale non-invasive measurement of
      magnetic fields generated by neural currents in the brain. However, localization
      of the underlying current sources is ambiguous due to the so-called inverse
      problem. The most widely used source localization methods (i.e., minimum-norm and
      minimum-current estimates (MNE and MCE) and equivalent current dipole (ECD)
      fitting) require ad hoc determination of the cortical current distribution (l(2)
      , l(1)-norm priors and point-sized dipolar, respectively). In this article, we
      perform a Bayesian analysis of the MEG inverse problem with l(p)-norm priors for
      the current sources. This way, we circumvent the arbitrary choice between l(1)-
      and l(2)-norm prior, which is instead rendered automatically based on the data.
      By obtaining numerical samples from the joint posterior probability distribution
      of the source current parameters and model hyperparameters (such as the l(p)-norm
      order p) using Markov chain Monte Carlo (MCMC) methods, we calculated the spatial
      inverse estimates as expectation values of the source current parameters
      integrated over the hyperparameters. Real MEG data and simulated (known) source
      currents with realistic MRI-based cortical geometry and 306-channel MEG sensor
      array were used. While the proposed model is sensitive to source space
      discretization size and computationally rather heavy, it is mathematically
      straightforward, thus allowing incorporation of, for instance, a priori
      functional magnetic resonance imaging (fMRI) information.

PMID- 15955498
TI  - Omission of serial arterial blood sampling in neuroreceptor imaging with
      independent component analysis.
AB  - We have previously proposed a statistical method for extracting a plasma time
      activity curve (pTAC) from dynamic PET images, named EPICA, for kinetic analysis
      of cerebral glucose metabolism. We assumed that the dynamic PET images consist of
      a blood-related component and a tissue-related component which are spatially
      independent in a statistical sense. The aim of this study is to investigate the
      utility of EPICA in imaging total distribution volume (DVt) and binding potential
      (BP) with Logan plots in a neuroreceptor mapping study. We applied EPICA to
      dynamic [(11)C]MPDX PET images in 25 subjects, including healthy subjects and
      patients with brain diseases, and validated the estimated pTACs. [11C]MPDX is a
      newly developed radiopharmaceutical for mapping cerebral adenosine A1 receptors.
      EPICA successfully extracted pTAC for all 25 subjects. Parametric images of DVts
      were estimated by applying Logan plots with the EPICA-estimated pTAC and then
      used to define a reference region. The BPs estimated using EPICA were evaluated
      in 18 subjects by ROI-based comparison with those obtained using the nonlinear
      least squares method (NLSM). The calculated BPs were identical to the estimates
      using NLSM in each subject. We conclude that EPICA is a promising technique that
      generates parametric images of DVt and BP in neuroreceptor mapping without
      requiring arterial blood sampling.

PMID- 15955499
TI  - Frontal circuitry degradation marks healthy adult aging: Evidence from diffusion
      tensor imaging.
AB  - In vivo study of white matter microstructural integrity through magnetic
      resonance diffusion tensor imaging (DTI) permits examination of degradation of
      axonal circuitry that may underlie functional decline of frontally-based
      processes in normal adult aging. Determination of the pattern of age-related
      degradation of white matter microstructure requires quantitative comparison of
      the rostral-caudal and superior-inferior extents of the brain's white matter. To
      date, this has not been accomplished, probably because of significant artifacts
      from spatial distortion and poor signal resolution that precludes accurate
      analysis in prefrontal and inferior brain regions. Here, we report a profile
      analysis of the integrity of white matter microstructure across the
      supratentorium and in selected focal regions using DTI data collected at high
      field strength (3 T), with isotropic voxel acquisition, and an analysis based on
      a concurrently-acquired field map to permit accurate quantification of artifact
      prone, anterior and inferior brain regions. The groups comprised 10 younger and
      10 older individuals; all were high functioning, highly educated, and in
      excellent health. The DTI profile analysis revealed a robust frontal distribution
      of low white matter anisotropy and high bulk mean diffusivity in healthy older
      compared with younger adults. In contrast to frontal fiber systems, posterior
      systems were largely preserved with age. A second analysis, based on focal
      samples of FA, confirmed that the age-related FA decline was restricted to
      frontal regions, leaving posterior and inferior brain regions relatively intact.
      The selective decline of anterior anisotropy with advancing age provides evidence
      for the potential of a microstructural white matter mechanism for the commonly
      observed decline in frontally-based functions.

PMID- 15955500
TI  - Age- and sex-related effects on the neuroanatomy of healthy elderly.
AB  - Effects of age and sex, and their interaction on the structural brain anatomy of
      healthy elderly were assessed thanks to a cross-sectional study of a cohort of
      662 subjects aged from 63 to 75 years. T1- and T2-weighted MRI scans were
      acquired in each subject and further processed using a voxel-based approach that
      was optimized for the identification of the cerebrospinal fluid (CSF)
      compartment. Analysis of covariance revealed a classical neuroanatomy sexual
      dimorphism, men exhibiting larger gray matter (GM), white matter (WM), and CSF
      compartment volumes, together with larger WM and CSF fractions, whereas women
      showed larger GM fraction. GM and WM were found to significantly decrease with
      age, while CSF volume significantly increased. Tissue probability map analysis
      showed that the highest rates of GM atrophy in this age range were localized in
      primary cortices, the angular and superior parietal gyri, the orbital part of the
      prefrontal cortex, and in the hippocampal region. There was no significant
      interaction between "Sex" and "Age" for any of the tissue volumes, as well as for
      any of the tissue probability maps. These findings indicate that brain atrophy
      during the seventh and eighth decades of life is ubiquitous and proceeds at a
      rate that is not modulated by "Sex".

PMID- 15955501
TI  - FDG PET in the differential diagnosis of parkinsonian disorders.
AB  - The differential diagnosis of parkinsonian disorders can be challenging,
      especially early in the disease course. PET imaging with [(18)F]
      fluorodeoxyglucose (FDG) has been used to identify characteristic patterns of
      regional glucose metabolism in patient cohorts with idiopathic Parkinson's
      disease (PD), as well as variant forms of parkinsonism such as multiple system
      atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal
      degeneration (CBGD). In this study, we assessed the utility of FDG PET in the
      differential diagnosis of individual patients with clinical parkinsonism. 135
      parkinsonian patients were referred for FDG PET to determine whether their
      diagnosis could be made accurately based upon their scans. Imaging-based
      diagnosis was obtained by visual assessment of the individual scans and also by
      computer-assisted interpretation. The results were compared with 2-year follow-up
      clinical assessments made by independent movement disorders specialists who were
      blinded to the original PET findings. We found that blinded computer assessment
      agreed with clinical diagnosis in 92.4% of all subjects (97.7% early PD, 91.6%
      late PD, 96% MSA, 85% PSP, 90.1% CBGD, 86.5% healthy control subjects).
      Concordance of visual inspection with clinical diagnosis was achieved in 85.4% of
      the patients scanned (88.4% early PD, 97.2% late PD, 76% MSA, 60% PSP, 90.9%
      CBGD, 90.9% healthy control subjects). This study demonstrates that FDG PET
      performed at the time of initial referral for parkinsonism accurately predicted
      the clinical diagnosis of individual patients made at subsequent follow-up.
      Computer-assisted methodologies may be particularly helpful in situations where
      experienced readers of FDG PET images are not readily available.

PMID- 15955502
TI  - Delayed hemodynamic responses in schizophrenia.
AB  - While there are many reports of reduced amplitude of hemodynamic responses in
      schizophrenia, there are no reports of delayed hemodynamic responses, in spite of
      event-related brain potential (ERP) evidence of slowed neural responses.
      Recently, Henson et al. (2002) [Henson, R., Price, C., Rugg, M., Turner, R.,
      Friston, K., 2002. Detecting latency differences in event-related BOLD responses:
      application to words versus nonwords and initial versus repeated face
      presentations. NeuroImage, 15:83-97] proposed a new method for testing small
      latency effects (<2 s) in hemodynamic responses. fMRI data were collected during
      a visual oddball task with infrequent (12%) targets (K) and frequent (88%)
      standards (X), presented every 1-3 s pseudorandomly, with 7-24 s between targets.
      SPM99 yielded parameter estimates for the hemodynamic response and its temporal
      derivative (TD). Beta images reflecting hemodynamic response magnitude to target
      stimuli were minimally thresholded (P < 0.05, uncorrected), and latencies were
      estimated for surviving voxels using TD and hemodynamic response beta values. DSM
      IV schizophrenia patients (n = 12) and sex- and age-matched healthy control
      subjects (n = 12) were recruited from the community. Although groups differed
      only minimally in activation height, hemodynamic responses were significantly
      delayed in basal ganglia, thalamus, and anterior cingulate in patients with
      schizophrenia. Psychomotor slowing reflected in reaction times to targets
      recorded outside the magnet was related to hemodynamic slowing in basal ganglia,
      anterior cingulate, thalamus, as well as left cerebellum in controls. Delays in
      the hemodynamic response have far-reaching implications for understanding the
      pathophysiology of schizophrenia from slowed neural responses to slowed substrate
      delivery, and depending of the degree of delay, may raise methodological issues
      regarding modeling hemodynamic responses in patients and controls.

PMID- 15955503
TI  - Functional network in the prefrontal cortex during episodic memory retrieval.
AB  - A recent consistent finding in neuroimaging studies of human memory is that the
      prefrontal cortex (PFC) is activated during episodic memory retrieval. To date,
      however, there has been no direct evidence to explain how activity in the right
      and left PFC and in the anterior and posterior PFC are functionally
      interconnected. The goal of the present study was to obtain such evidence by
      event-related functional magnetic resonance imaging (MRI) and the functional
      connectivity method. Subjects were first asked to try to remember a series of
      associate-word lists outside the MRI scanner in preparation for a later
      recognition test. In the MRI scanning phase, they were asked to make recognition
      judgments in regard to old words, semantically related lure words, and unrelated
      new words. The analysis of functional connectivity revealed that the posterior
      PFC in each hemisphere had strong functional interconnections with the
      contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only
      weak functional interconnections with the contralateral anterior PFC. No strong
      functional interconnections were found between the anterior and posterior PFC in
      either hemisphere. These findings support the hypothesis of an associative
      contribution of the bilateral posterior PFC to episodic memory retrieval and a
      dissociative contribution of the bilateral anterior PFC.

PMID- 15955504
TI  - Functional MRI BOLD response to Tower of London performance of first-episode
      schizophrenia patients using cortical pattern matching.
AB  - Due to its three-dimensional folding pattern, the human neocortex poses a
      challenge for accurate co-registration of grouped functional brain imaging data.
      The present study addressed this problem by employing three-dimensional continuum
      mechanical image-warping techniques to derive average anatomical representations
      for co-registration of functional magnetic resonance brain imaging data obtained
      from 10 male first-episode schizophrenia patients and 10 age-matched male healthy
      volunteers while they performed a version of the Tower of London task. This novel
      technique produced an equivalent representation of blood oxygenation level
      dependent (BOLD) response across hemispheres, cortical regions, and groups,
      respectively, when compared to intensity average co-registration, using a
      deformable Brodmann area atlas as anatomical reference. Somewhat closer
      association of Brodmann area boundaries with primary visual and auditory areas
      was evident using the gyral pattern average model. Statistically-thresholded BOLD
      cluster data confirmed predominantly bilateral prefrontal and parietal, right
      frontal and dorsolateral prefrontal, and left occipital activation in healthy
      subjects, while patients' hemispheric dominance pattern was diminished or
      reversed, particularly decreasing cortical BOLD response with increasing task
      difficulty in the right superior temporal gyrus. Reduced regional gray matter
      thickness correlated with reduced left-hemispheric prefrontal/frontal and
      bilateral parietal BOLD activation in patients. This is the first study
      demonstrating that reduction of regional gray matter in first-episode
      schizophrenia patients is associated with impaired brain function when performing
      the Tower of London task, and supports previous findings of impaired executive
      attention and working memory in schizophrenia.

PMID- 15955505
TI  - Changes in brain electrical activity during extended continuous word recognition.
AB  - Twenty healthy subjects (10 men, 10 women) participated in an EEG study with an
      extended continuous recognition memory task, in which each of 30 words was
      randomly shown 10 times and subjects were required to make old vs. new decisions.
      Both event-related brain potentials (ERPs) and induced band power (IBP) were
      investigated. We hypothesized that repeated presentations affect recollection
      rather than familiarity. For the 300- to 500-ms time window, an 'old/new' ERP
      effect was found for the first vs. second word presentations. The correct
      recognition of an 'old' word was associated with a more positive waveform than
      the correct identification of a new word. The old/new effect was most pronounced
      at and around the midline parietal electrode position. For the 500- to 800-ms
      time window, a linear repetition effect was found for multiple word repetitions.
      Correct recognition after an increasing number of repetitions was associated with
      increasing positivity. The multiple repetitions effect was most pronounced at the
      midline central (Cz) and fronto-central (FCz) electrode positions and reflects a
      graded recollection process: the stronger the memory trace grows, the more
      positive the ERP in the 500- to 800-ms time window. The ERP results support a
      dual-processing model, with familiarity being discernable from a more graded
      recollection state that depends on memory strengths. For IBP, we found 'old/new'
      effects for the lower-2 alpha, theta, and delta bands, with higher bandpower
      during 'old' words. The lower-2 alpha 'old/new' effect most probably reflects
      attentional processes, whereas the theta and delta effects reflect encoding and
      retrieval processes. Upon repeated word presentations, the magnitude of induced
      delta power in the 375- to 750-ms time window diminished linearly. Correlation
      analysis suggests that decreased delta power is moderately associated with faster
      decision speed and higher accuracy.

PMID- 15955506
TI  - Motion or activity: their role in intra- and inter-subject variation in fMRI.
AB  - Functional MRI (fMRI) carries the potential for non-invasive measurements of
      brain activity. Typically, what are referred to as activation images are actually
      thresholded statistical parametric maps. These maps possess large inter-session
      variability. This is especially problematic when applying fMRI to pre-surgical
      planning because of a higher requirement for intra-subject precision. The purpose
      of this study was to investigate the impact of residual movement artefacts on
      intra-subject and inter-subject variability in the observed fMRI activation. Ten
      subjects were examined using three different word-generation tasks. Two of the
      subjects were examined 10 times on 10 different days using the same paradigms. We
      systematically investigated one approach of correcting for residual movement
      effects: the inclusion of regressors describing movement-related effects in the
      design matrix of a General Linear Model (GLM). The data were analysed with and
      without modeling the residual movement artefacts and the impact on inter-session
      variance was assessed using F-contrasts. Inclusion of motion parameters in the
      analysis significantly reduced both the intra-subject as well as the inter
      subject-variance.

PMID- 15955507
TI  - Sex differences in N-acetylaspartate correlates of general intelligence: an 1H
      MRS study of normal human brain.
AB  - Researchers have long attempted to determine brain correlates of intelligence
      using available neuroimaging technology including CT, MRI, PET, and fMRI.
      Although structural and functional imaging techniques are well suited to assess
      gross cortical regions associated with intelligence, the integrity and
      functioning of underlying white matter networks critical to coordinated cortical
      integration remain comparatively understudied. A relatively recent neuroimaging
      advance is magnetic resonance spectroscopy (MRS) which allows for interrogation
      of biochemical substrates of brain structure and function in vivo. In this study,
      we examined twenty-seven normal control subjects (17 male, 10 female) to
      determine whether N-acetylaspartate (NAA), a metabolite found primarily within
      neurons, is related to intelligence as assessed by the Wechsler Adult
      Intelligence Scale-III. Of the three white matter regions studied (i.e., left
      frontal, right frontal, left occipito-parietal), we found that a model including
      only left occipito-parietal white matter predicted intellectual performance
      [F(1,25) = 8.65, P = .007; r2 = .26], providing regional specificity to our
      previous findings of NAA-IQ relationships. Moreover, we found that a complex
      combination of left frontal and left occipito-parietal NAA strongly predicted
      performance in women, but not men [F(2,7) = 21.84, P < .001; adjusted r2 = .82].
      Our results highlight a biochemical substrate of normal intellectual performance,
      mediated by sex, within white matter association fibers linking posterior to
      frontal brain regions.

PMID- 15955508
TI  - The importance of time scale and multiple refugia: incipient speciation and
      admixture of lineages in the butterfly Erebia triaria (Nymphalidae).
AB  - Evidence of four different Quaternary glacial stages has been found in NW Iberia.
      The different magnitude of these episodes probably conditioned the distribution
      of currently montane species. We examined if the population history of NW Iberian
      Erebia triaria butterflies reflected such an influence of different glacial
      stages. We also investigated whether these populations were post-glacially
      colonised from a single refugial area or several sources. For this, we performed
      phylogenetic analyses and coalescence simulations on mitochondrial DNA sequences
      of individuals from five NW Iberian locations. We analysed three additional
      populations as reference, i.e., Central Spain, the Pyrenees, and the Alps. One of
      the NW Iberian populations, a subspecies endemic to a particular mountain range
      (Xistral), showed a high level of genetic divergence from all other populations,
      regardless of their geographic distance. Isolation after an ancient glacial
      stage, and followed by allopatric differentiation, may account for such high
      differentiation. The genetic pattern shown by the rest of the NW Iberian
      population samples consisted of two lineages, likely reflecting that the
      ancestors of these populations sought for refuge in at least two different areas
      during a subsequent glacial stage. We showed evidence of both temporal and
      spatial divisions in the phylogeography of these butterflies. The congruence of
      this pattern with the geological history suggests that the Iberian Peninsula
      hosted several refugial areas that differed in area and location depending on the
      glacial stage.

PMID- 15955509
TI  - Non-monophyletic taxa and cryptic species--evidence from a molecular phylogeny of
      leaf-warblers (Phylloscopus, Aves).
AB  - The avian taxa Cryptigata and Acanthopneuste have been treated either as
      subgenera within Phylloscopus (leaf-warblers), or as a distinct genus and an
      informal group, respectively. The circumscriptions of these taxa have varied
      between authors. We estimated the phylogeny, based on the mitochondrial
      cytochrome b and 12S genes and the nuclear myoglobin intron II, of all except two
      of the species placed in the Cryptigata and Acanthopneuste groups, as well as two
      recently described species and representatives of all subgenera and major clades
      in Phylloscopus and Seicercus recognized by previous studies. Neither Cryptigata
      nor Acanthopneuste is found to be monophyletic. The polytypic species P.
      reguloides and P. davisoni show deep divergences between some of their respective
      subspecies, and the latter species is non-monophyletic. We propose that the
      former be split into three species and the latter into two species. Seicercus
      xanthoschistos is nested in a clade that includes only Phylloscopus, and we
      recommend that it be placed in Phylloscopus. The rate of morphological divergence
      varies considerably among the taxa in this study. Our results emphasize the
      importance of dense taxon sampling in intrageneric phylogenetic studies.

PMID- 15955510
TI  - Impact of glaciations and geographic distance on the genetic structure of a
      tropical estuarine fish, Ethmalosa fimbriata (Clupeidae, S. Bowdich, 1825).
AB  - We assayed the mtDNA phylogeography [196 base pairs (bp) of the cytochrome b] and
      population structure (n = 680) in the estuarine fish, Ethmalosa fimbriata, from
      its whole distribution range: 14 locations along the West African coasts were
      sampled. Specifically, we considered Pleistocene glaciations as well as the
      hydrodynamics and climatic conditions of the estuarine environments in order to
      identify the main evolutionary forces that have shaped the genetic variation in
      mtDNA, i.e., the contemporary or the historical gene flow. There was an overall
      significant population differentiation among estuaries (Fst = 0.10). Although E.
      fimbriata showed a significant pattern of isolation by distance over the entire
      sampled range, this genetic structure did not mirror contemporary gene flow but
      the colonization sequence of the present distribution range. Finally, the mtDNA
      genetic structure traced the past historic dispersion that occurred at the end of
      the Pleistocene glaciations. The central part of the present distribution area
      was probably the species origin and due to difference in the historic migration
      rate northward and southward, isolation of a South group occurred first, 110,000
      190,000 years ago, before the divergence of the North group 47,000-82,000 years
      ago.

PMID- 15955512
TI  - Phylogenetic relationships and evolutionary traits in Ranunculus s.l.
      (Ranunculaceae) inferred from ITS sequence analysis.
AB  - Ranunculus is a large genus with a worldwide distribution. Phylogenetic analyses
      of c. 200 species of Ranunculus s.l. based on sequences of the nrITS using
      maximum parsimony and Bayesian inference yielded high congruence with previous
      cpDNA restriction site analyses, but strongly contradict previous
      classifications. A large core clade including Ranunculus subg. Ranunculus, subg.
      Batrachium, subg. Crymodes p.p., Ceratocephala, Myosurus, and Aphanostemma is
      separated from R. subg. Ficaria, subg. Pallasiantha, subg. Coptidium, subg.
      Crymodes p.p., Halerpestes, Peltocalathos, Callianthemoides, and Arcteranthis.
      Within the core clade, 19 clades can be described with morphological and
      karyological features. Several sections are not monophyletic. Parallel evolution
      of morphological characters in adaptation to climatic conditions may be a reason
      for incongruence of molecular data and morphology-based classifications. In some
      mountainous regions, groups of closely related species may have originated from
      adaptive radiation and rapid speciation. Split decomposition analysis indicated
      complex patterns of relationship and suggested hybridization in the apomictic R.
      auricomus complex, R. subg. Batrachium, and the white-flowering European alpines.
      The evolutionary success of the genus might be due to a combination of
      morphological plasticity and adaptations, hybridization and polyploidy as
      important factors for regional diversification, and a broad range of reproductive
      strategies.

PMID- 15955513
TI  - High divergence among Drosophila simulans mitochondrial haplogroups arose in
      midst of long term purifying selection.
AB  - We characterize the type of selection acting within and among mitochondrial
      lineages in five closely related Drosophila species. We focus on D. simulans,
      where three genetically distinct mitochondrial haplogroups show high
      interhaplogroup divergence and low intrahaplogroup polymorphism. Using maximum
      likelihood models we find that the branches leading to these three distinct
      mitochondrial groups show a significantly reduced rate of nonsynonymous relative
      to synonymous substitution. This interhaplogroup rate is significantly reduced
      compared to the intrahaplogroup rate, and closely resembles the rate observed
      between distinct species. The data suggest that slightly deleterious mutations
      segregating within D. simulans haplogroups are removed by selection prior to
      their fixation among haplogroups. We explore several hypotheses to explain how
      lineages within a single species can be compatible with this model of slightly
      deleterious mutation. The most likely hypothesis is that D. simulans haplogroups
      have persisted in isolation, perhaps due to association with the bacterial
      symbiont Wolbachia and/or demographic history, introducing a bias against the
      fixation of slightly deleterious mutations.

PMID- 15955511
TI  - Phylogeny and comparative biogeography of Pionopsitta parrots and Pteroglossus
      toucans.
AB  - Studies of Neotropical birds, and their distributions and areas of endemism, in
      particular, have been central in the formulation of hypotheses proposed to
      explain the high species diversity in the Neotropics. We used mtDNA sequence data
      (ATPase 6 and 8, COI, and cyt b) to reconstruct the species-level phylogenies for
      two genera, Pionopsitta (Aves: Psittacidae) and Pteroglossus (Aves:
      Ramphastidae), compare our results with previous morphology-based phylogenetic
      analyses, and estimate the absolute timing of lineage and biogeographic
      divergences. Both the Pionopsitta and Pteroglossus phylogenies support a
      hypothesis of area relationships in which a divergence of the Serra do Mar
      (Atlantic Forest, Brazil) region of endemism is followed by the divergence of cis
      and trans-Andean regions, then a split between the upper and lower Amazon basin,
      next the divergence of the Guyana area, and finally diversification of taxa in
      the upper Amazon basin's areas of endemism. Phylogenies of both genera support a
      hypothesis of area relationships that is similar to that proposed by Prum [XIX
      International Ornithological Congress (1988), 2562] for high-vagility species,
      but while they agree on the relative timing of area divergence (vicariance)
      events, they yield different absolute time estimates for those divergences when
      the typical avian mtDNA clock calibration is used. Taken at face value, the time
      estimates indicate that both genera began to diversify before the start of the
      Pleistocene, and that climatic and habitat shifts alone do not account for the
      diversification of these taxa.

PMID- 15955514
TI  - Complex evolutionary history of a Neotropical lowland forest bird (Lepidothrix
      coronata) and its implications for historical hypotheses of the origin of
      Neotropical avian diversity.
AB  - Here we apply a combination of phylogeographic and historical demographic
      analyses to the study of mtDNA sequence variation within the Blue-crowned Manakin
      (Lepidothrix coronata), a widespread Neotropical bird. A high degree of
      phylogeographic structure allowed us to demonstrate that several vicariant
      events, including Andean uplift, the formation of riverine barriers, and
      climatically induced vegetational shifts, as well as a non-vicariant process,
      range expansion, have all acted, at varying spatial and temporal scales, to
      influence genetic structure within L. coronata, suggesting that current
      historical hypotheses of the origin of Neotropical avian diversity that focus on
      single vicariant mechanisms may be overly simplistic. Our data also support an
      origin (>2 mybp) that is substantially older than the late Pleistocene for the
      genetic structure within this species and indicate that phylogeographic patterns
      within the species are not concordant with plumage-based subspecific taxonomy.
      These data add to a growing body of evidence suggesting that the origin of
      several Neotropical avian species may have occurred in the mid-Pliocene, thus,
      geological arguments surrounding putative Pleistocene vicariant events, while
      interesting in their own right, may have little relevance to Neotropical avian
      diversification at the species level.

PMID- 15955515
TI  - Molecular phylogeny of the African pygmy mice, subgenus Nannomys (Rodentia,
      Murinae, Mus): implications for chromosomal evolution.
AB  - Molecular phylogenies based on sequences of mitochondrial cytochrome b and
      nuclear IRBP genes are assessed on a comprehensive taxonomic sampling of African
      pygmy mice (subgenus Nannomys of the genus Mus). They represent a taxonomically
      diversified group of morphologically similar species, and exhibit an important
      chromosomal diversity, particularly involving sex-autosome translocations, one of
      the rarest and most deleterious chromosomal changes among mammals. The results
      show that the species sampled are genetically well differentiated, and that
      chromosomal rearrangements offer accurate diagnostic characters for
      discriminating most species. Furthermore, the species carrying different sex
      autosome translocations appear monophyletic, suggesting that a genome
      modification allowing a higher rate of occurrence and/or fixation of such
      translocations took place, leading to the emergence of this lineage. In addition
      to taxonomic and biogeographical clarifications, we provide a temporal framework
      within which patterns of genic and chromosomal evolution are discussed.

PMID- 15955516
TI  - Phylogenetic relationships and evolutionary history of the reef fish family
      Labridae.
AB  - The family Labridae (including scarines and odacines) contains 82 genera and
      about 600 species of fishes that inhabit coastal and continental shelf waters in
      tropical and temperate oceans throughout the world. The Labridae (the wrasses) is
      the fifth largest fish family and second largest marine fish family, and is one
      of the most morphologically and ecologically diversified families of fishes in
      size, shape, and color. Labrid phylogeny is a long-standing problem in
      ichthyology that is part of the larger question of relationships within the
      suborder Labroidei. A phylogenetic analysis of labrids was conducted to
      investigate relationships among the six classical tribes of wrasses, the
      affinities of the wrasses to the parrotfishes (scarines), and the broad
      phylogenetic structure among labrid genera. Four gene fragments were sequenced
      from 98 fish species, including 84 labrid fishes and 14 outgroup taxa. Taxa were
      chosen from all major labrid clades and most major global ocean regions where
      labrid fishes exist, as well as cichlid, pomacentrid, and embiotocid outgroups.
      From the mitochondrial genome we sequenced portions of 12S rRNA (1000 bp) and 16S
      rRNA (585 bp), which were aligned by using a secondary structure model. From the
      nuclear genome, we sequenced part of the protein-coding genes RAG2 (846 bp) and
      Tmo4C4 (541 bp). Maximum likelihood, maximum parsimony, and Bayesian analyses on
      the resulting 2972 bp of DNA sequence produced similar topologies that confirm
      the monophyly of a family Labridae that includes the parrotfishes and
      butterfishes and strong support for many previously identified taxonomic
      subgroups. The tribe Hypsigenyini (hogfishes, tuskfishes) is the sister group to
      the remaining labrids and includes odacines and the chisel-tooth wrasse Pseudodax
      moluccanus, a species previously considered close to scarines. Cheilines and
      scarines are sister-groups, closely related to the temperate Labrini, and
      pseudocheilines and cheilines are split in all phylogenies. The razorfishes
      (novaculines) and temperate pseudolabrines form successive sister clades to the
      large crown group radiation of the Julidini. The cleaner wrasses (Labrichthyini)
      are nested within this radiation and several julidine genera do not appear to be
      monophyletic (e.g., Coris and Halichoeres). Invasion of temperate water by this
      predominantly tropical group has occurred multiple times and the reconstruction
      of biogeography assuming an Indo-Pacific ancestor results in five different
      lineages invading the Atlantic/Caribbean region. Functional novelties in the
      feeding apparatus have allowed labrid fishes to occupy nearly every feeding guild
      in reef environments, and trophic variation is a central axis of diversification
      in this family.

PMID- 15955517
TI  - Phylogeny and character evolution of endemic Australian carabid beetles of the
      genus Pamborus based on mitochondrial and nuclear gene sequences.
AB  - The phylogeny of carabid beetles in the genus Pamborus (Coleoptera: Carabidae),
      which is endemic to Australia, was studied using one nuclear (phosphoenolpyruvate
      carboxykinase) and two mitochondrial (16S ribosomal RNA and NADH dehydrogenase
      subunit 5) gene sequences, with a cladistic analysis of morphological data.
      Fourteen species that were morphologically distinguishable were used as ingroup
      taxa, and Maoripamborus fairburni from New Zealand was assigned as the outgroup.
      Simultaneous analysis of three gene sequences resulted in well-resolved trees
      that were largely consistent with the cladogram generated from the morphological
      data. Based on a clock-like tree calibrated to the New Zealand
      Australia/Antarctica split 85 million years ago, it was estimated that extant
      Pamborus differentiated after the Oligocene, primarily since the mid-Miocene with
      the onset of a more arid climate and forest fragmentation in Australia. The
      ancestral Pamborus may have been small, whereas medium to large Pamborus species
      with exaggerated male genitalia constitute derived groups and are now dominant.

PMID- 15955518
TI  - Testing species boundaries in the Antrodiaetus unicolor complex (Araneae:
      Mygalomorphae: Antrodiaetidae): "paraphyly" and cryptic diversity.
AB  - The inability to correctly identify species has far reaching implications in
      nearly all areas of biology, yet few studies investigate methods for delineating
      species boundaries. Moreover, once these boundaries have been hypothesized,
      little thought has been given to how these constructs can be further evaluated.
      We employ a molecular phylogenetic approach using nuclear 28S rRNA and
      mitochondrial cytochrome c oxidase subunit I genes to test the general efficacy
      of species boundaries in the Antrodiaetus unicolor spider species complex. Our
      analyses provide evidence that An. unicolor is "paraphyletic" with respect to An.
      microunicolor, indicating that morphological criteria used to delineate species
      boundaries undersplits actual species-level diversity in this group of spiders.
      These analyses also demonstrate that individuals from geographically proximate
      populations sometimes exhibit considerable molecular divergence, strongly
      suggesting that An. unicolor is a cryptic species complex. Finally, this
      molecular approach has provided the phylogenetic framework that is necessary to
      begin interpreting the vast amount of morphological variation observed in these
      spiders based upon findings from previous studies. Our approach using multiple
      genes appears to be a rigorous method to critically examine species boundaries
      originally based on traditional morphological approaches to spider taxonomy.

PMID- 15955520
TI  - Passenger complaints about driver behaviors.
AB  - Fifty-two couples were surveyed about their behavior while driving together. Each
      was asked to individually rate the driver's behavior, the passenger's amount of
      complaining about the driver's behavior, the effect of that complaining on the
      driver, the driver's use of vengeance while driving, and the driver's ability and
      safety. Drivers and passengers gave similar responses: the riskier the driver's
      behavior, the more the passenger complained. The more the passenger complained,
      the less both reported that it helped. Judged ability of the driver was not
      related to the driver's risky behavior by either the drivers or passengers,
      although passengers, but not drivers, saw more risky driving behaviors as less
      safe.

PMID- 15955519
TI  - Molecular phylogeny of the medaka fishes genus Oryzias (Beloniformes:
      Adrianichthyidae) based on nuclear and mitochondrial DNA sequences.
AB  - The phylogenetic relationships among medaka fishes of 2 genera, Oryzias and
      Xenopoecilus, were studied using the nuclear tyrosinase and mitochondrial 12S and
      16S rRNA genes. Of the 23 species currently described for these genera, 13
      species of Oryzias and 2 species of Xenopoecilus were examined. The tree
      topologies obtained from the nuclear and mitochondrial data were consistent,
      indicating that Xenopoecilus is a polyphyletic genus nested within Oryzias. This
      result suggested the necessity for a systematic study and taxonomic revision of
      Xenopoecilus. The combined data analysis of all data partitions resulted in a
      well-resolved tree, with most internal branches supported by high statistical
      values. Based on our combined data phylogeny, we divided the Oryzias species into
      three major species groups, namely the latipes, javanicus, and celebensis groups.
      These three groups corresponded to the three chromosomal groups (biarmed,
      monoarmed, and fused chromosome groups) previously proposed from karyological
      analyses. The phylogeographic pattern suggests historical vicariance between
      Sulawesi Island and the continental shelf.

PMID- 15955521
TI  - Behavior differences in drivers with attention deficit hyperactivity disorder:
      the driving behavior questionnaire.
AB  - Attention deficit hyperactivity disorder (ADHD) has been linked to an increased
      number of driving citations, especially for speeding and a four-fold increase in
      accident risk. Using three factors--errors, lapses and violations--found in prior
      work, we ran regression analyses to explore the impact of ADHD status, gender and
      age on error, lapse and violation report scores. The results indicate that ADHD
      status is positively and significantly related to error, lapse and violation
      scores. In the cases of errors and violations, however, interactions between ADHD
      status and age are significant such that older participants with ADHD do not
      differ statistically from controls. There were no significant effects of age on
      error, lapse or violation scores for control participants. Consistent with
      earlier work, gender was significantly related to violation scores, but not to
      errors or lapses, such that men were more likely than women to report higher
      violation scores, controlling for ADHD status and age. We consider possible
      explanations for these findings and discuss the implications of these results for
      the accident risk of individuals with ADHD as they age.

PMID- 15955522
TI  - Trypanosoma cruzi: the effects of dehydroepiandrosterone (DHEA) treatment during
      experimental infection.
AB  - The aim of this study was to evaluate the efficacy of the immunomodulator
      dehydroepiandrosterone (DHEA) in the treatment of Trypanosoma cruzi infection and
      the possible biochemistry alterations in male and female Wistar rats. DHEA also
      known as the steroid of multiple actions has attracted distinct medical areas.
      Prior studies show that DHEA enhances immune responses against a wide range of
      viral, bacterial and parasitic pathogens. Furthermore, administration of DHEA
      seems to protect animals against obesity and diabetes. Male animals subcutaneous
      treated with 40 mg/kg body weight/day of DHEA displayed a significant reduction
      in blood parasites during parasitaemia peak, when compared to untreated animals
      (P<0.001). For female group parasitaemia was also reduced although values are not
      statistically significant (P>0.05). Sexual dimorphism was also observed, since
      females displayed lesser parasitaemia levels compared to males group treated
      (P>0.05) and untreated (P<0.001). Enhanced leucocytes number was observed in
      control females when compared to control males (P<0.05). DHEA treatment did not
      triggered any significant alterations in leucocytes levels (P>0.05). DHEA
      administration induced an enhanced number of macrophages in infected male
      (P<0.01). DHEA administration causes a decrease in glucose (P<0.001). Cholesterol
      and tryglicerides levels did not display results statistically significant
      (P>0.05) during the treatment. These results suggest that DHEA treatment enhances
      the immune response as evidenced here by reduced levels of parasites. Up
      regulation of the immune system by exogenous DHEA may be useful in the treatment
      of American tripanosomiasis.

PMID- 15955523
TI  - Malaria vaccines. Evaluation and implementation.
AB  - Development of an effective malaria vaccine that could be deployed widely in
      endemic areas has proved to be more difficult than was anticipated, when the
      first clinical trials of malaria vaccines were conducted 30 years ago.
      Substantial progress has been made during the past few years and one candidate
      vaccine, RTS,S/AS02, shows promise. However, during the period that malaria
      vaccine development has been taking place, alternative methods of malaria control
      including insecticide treated bednets and intermittent preventive treatment in
      infancy and childhood have been developed and shown to be partially effective.
      Malaria vaccines will need to be more effective or more cost effective than these
      alternative control strategies or be able to provide substantial added value,
      when deployed with them if they are to be adopted widely.

PMID- 15955524
TI  - FMDV-2A sequence and protein arrangement contribute to functionality of CYP2B1
      reporter fusion protein.
AB  - Two optimized forms of green fluorescence proteins (GFP), enhanced GFP (EGFP) and
      humanized Renilla GFP (hrGFP), were used to track expression of cytochrome P450
      2B1 (CYP2B1), an endoplasmic reticulum membrane-bound protein. In transiently
      expressing HEK293 cells we show that CYP2B1-GFP fusion proteins are stable and
      functional, whereas the vice-versa-arranged GFP-CYP2B1 fusions are not. The
      CYP2B1-hrGFP fusion protein is characterized by reduction in mean fluorescence
      intensity (MFI) to less than 20% of that of the hrGFP protein alone, accompanied
      by a 50% loss of CYP2B1 activity. Exchanging the linker for an alpha-helical
      peptide structure between CYP2B1 and hrGFP does not improve fusion protein
      activity. Insertion of a short linker (five amino acids) increases reporter
      protein fluorescence intensity twofold without improving CYP2B1 activity.
      Introduction of the foot and mouth disease virus 2A sequence providing
      cotranslational cleavage led to an unstable hrGFP-2A protein, whereas the
      corresponding EGFP-2A protein was stable and yielded an MFI superior to those of
      all other fusion constructs tested. CYP2B1 activity of the EGFP-2A-CYP2B1 protein
      was in the range of that of the unmodified CYP2B1. These data indicate that the
      protein arrangement EGFP-2A-CYP2B1 is superior to others, since it is most active
      and visible, which is essential for an effective tracking of the CYP2B1 enzyme.

PMID- 15955525
TI  - Removal of phospholipid contaminants through precipitation of
      glycosylphosphatidylinositols.
AB  - Parasitic glycosylphosphatidylinositols (GPIs) are thought to be involved in
      induced cell signaling that leads to proinflammatory responses. Increasing
      interest in elucidation of the mechanisms involved in signaling pathways drives
      the finding of rapid and reliable methods to purify GPIs. GPIs are usually
      extracted using mixtures of chloroform/methanol/water, followed by a phase
      partition between water and water-saturated n-butanol. GPIs recovered in the
      butanol phase are separated by thin-layer chromatography, scraped, eluted from
      the silica, and used for studying the structure-function relationship. The
      presence of phospholipid contaminants or other hydrophobic components in the
      samples cannot be excluded. Furthermore, the standard procedures to purify GPIs
      harbor several drawbacks, including the need to handle large amounts of culture,
      poor yields, time-consuming, and interfering contaminants. Here we report on the
      development of a simple and reliable method to isolate and purify both free and
      bound GPIs from one cell pellet. We exploited the low solubility of GPIs in water
      saturated n-butanol to remove the phospholipid contaminants completely. After
      delipidation, GPI proteins were solubilized from the pellet using a mixture of
      organic solvent containing ethanol and water.

PMID- 15955526
TI  - Comparison of the lipid composition of porcine buccal and esophageal permeability
      barriers.
AB  - Pig esophageal mucosa has been shown to be a useful and practical substitute for
      buccal mucosa in in vitro permeability studies in that it offers a larger surface
      area and it is much easier to prepare. Further, the tissues demonstrate similar
      histological characteristics. The objectives of this work were to characterize
      the lipid composition of the esophageal mucosa, to compare it to that of the
      buccal tissue, and to correlate lipid composition with the membranes'
      permeability to fentanyl. The major lipid classes of buccal and esophageal
      epithelia were separated and analysed by automated multiple development high
      performance thin-layer chromatography (AMD-HPTLC). The two epithelia presented a
      very similar lipid pattern. In general, there were more polar lipids than non
      polar; glycosylceramides were relatively abundant whereas the amount of ceramides
      present was very small. The flux of fentanyl applied as the citrate in aqueous
      solution was comparable across the buccal and esophageal barriers. Lipid
      extraction provoked a significant increase in permeability. In conclusion, this
      research confirms the suitability of the esophageal mucosa as a model for buccal
      permeability studies.

PMID- 15955527
TI  - Interruption of the Calvin cycle inhibits the repair of Photosystem II from
      photodamage.
AB  - In photosynthetic organisms, impairment of the activities of enzymes in the
      Calvin cycle enhances the extent of photoinactivation of Photosystem II (PSII).
      We investigated the molecular mechanism responsible for this phenomenon in the
      unicellular green alga Chlamydomonas reinhardtii. When the Calvin cycle was
      interrupted by glycolaldehyde, which is known to inhibit phosphoribulokinase, the
      extent of photoinactivation of PSII was enhanced. The effect of glycolaldehyde
      was very similar to that of chloramphenicol, which inhibits protein synthesis de
      novo in chloroplasts. The interruption of the Calvin cycle by the introduction of
      a missense mutation into the gene for the large subunit of ribulose-1,5
      bisphosphate carboxylase/oxygenase (Rubisco) also enhanced the extent of
      photoinactivation of PSII. In such mutant 10-6C cells, neither glycolaldehyde nor
      chloramphenicol has any additional effect on photoinactivation. When wild-type
      cells were incubated under weak light after photodamage to PSII, the activity of
      PSII recovered gradually and reached a level close to the initial level. However,
      recovery was inhibited in wild-type cells by glycolaldehyde and was also
      inhibited in 10-6C cells. Radioactive labelling and Northern blotting
      demonstrated that the interruption of the Calvin cycle suppressed the synthesis
      de novo of chloroplast proteins, such as the D1 and D2 proteins, but did not
      affect the levels of psbA and psbD mRNAs. Our results suggest that the
      photoinactivation of PSII that is associated with the interruption of the Calvin
      cycle is attributable primarily to the inhibition of the protein synthesis
      dependent repair of PSII at the level of translation in chloroplasts.

PMID- 15955528
TI  - Comparative molecular dynamics simulations of uncomplexed, 'agonist-bound' and
      'antagonist-bound' alpha1A adrenoceptor models.
AB  - Molecular dynamics simulations (2 ns) were conducted on a homology model of the
      alpha1A adrenoceptor complexed with agonists and antagonists to examine the
      various receptor conformations induced. These simulations yield insights into the
      binding site interactions of the active and inactive states of the receptor.
      Furthermore, our analysis allowed for the selection of candidate sites for future
      mutagenesis experiments such as of Glu-180, which may be important for antagonist
      binding. The interactions of conserved residues of the DRY motif in TM-III and
      the NPxxY motif in TM-VII in the alpha1A adrenoceptor complexes were also
      examined. The major differences lie in the role of residue Arg-124, which for the
      agonist complexes formed additional interactions with residues of intracellular
      loops I and II. Alternatively, for the antagonist complexes, additional
      interactions were observed for Asn-322 with residues of TM-II and TM-VII.

PMID- 15955529
TI  - Influence of nonspecific reaction on determination of H2O2 using Trinder
      reagents.
AB  - BACKGROUND: We examined two enzymatic reagents for cholesterol measurement that
      contained cholesterol oxidase. One of the reagents gave higher values by up to 11
      mg/dl in samples of 109 out of 3119 patients examined. We found that the positive
      errors were caused by a nonspecific reaction that has not previously been
      recognized in the determination of H(2)O(2) using Trinder reagents, and we
      further discovered its mechanism. METHODS: We compared the total cholesterol
      concentration in 3119 patients between the 2 reagents. By examining the
      characteristics of the interferrent-susceptible reagent and affected patients'
      samples, we identified the cause and mechanism of the influence of the
      nonspecific reaction. RESULTS: The existence of potassium ferrocyanide in the
      reagent gave rise to positive errors when the concentration of unsaturated iron
      binding capacity (UIBC) in the patients' sample was <70 microg/dl. Moreover,
      ceruloplasmin in the patients' sample was found to cause a nonspecific reaction
      and its influence was proportional to the serum copper concentration. The two
      types of reagents compared in the present study included buffers with different
      metal chelating capacities; the one with the lower capacity gave an erroneous
      measurement. The buffer in the reagent without influence had been acting as a
      chelating agent. Therefore, the influence of the interferrent-susceptible reagent
      could be prevented by addition of a chelating agent (e.g. EDTA). CONCLUSIONS:
      Trinder reagents containing potassium ferrocyanide have been widely used for
      clinical diagnostic tests such as creatinine, uric acid and so on. These reagents
      would have similar problems. Some test items might have a greater influence than
      cholesterol reagent. Physicians should be aware of the risks of diagnostic
      mistakes due to these errors of measurement.

PMID- 15955530
TI  - Clp upregulates transcription of engA gene encoding a virulence factor in
      Xanthomonas campestris by direct binding to the upstream tandem Clp sites.
AB  - In Xanthomonas campestris, the causative agent of black rot in crucifers, the
      endoglucanase level is greatly decreased in the mutant deficient in Clp, a
      homologue of cyclic AMP receptor protein (CRP). It is established that Clp has
      the same DNA binding specificity as CRP at positions 5, 6, and 7 (GTG motif) of
      the DNA half site. In this study, the engA transcription initiation site was
      determined by the 5' RACE method, and two consensus Clp-binding sites, site I and
      site II centered at -69.5 and -42.5, respectively, were located. Transcriptional
      fusion assays indicated that Clp greatly activates engA transcription. Site
      directed mutagenesis indicated that position 5 of GTG motif in site II is
      essential for both DNA-protein complex formation in electrophoretic mobility
      shift assays and engA transcription in vivo. In addition, mutation at position 5
      of site I drastically reduces the promoter activity, indicating that binding of
      Clp to site I exerts a synergistic effect on the transcription activation by site
      II. engA appears to be the first X. campestris gene known to be activated by Clp
      via a direct binding to the promoter.

PMID- 15955532
TI  - The secondary electron acceptor of photosystem I in Gloeobacter violaceus PCC
      7421 is menaquinone-4 that is synthesized by a unique but unknown pathway.
AB  - The secondary electron acceptor of photosystem (PS) I in the cyanobacterium
      Gloeobacter violaceus PCC 7421 was identified as menaquinone-4 (MQ-4) by
      comparing high performance liquid chromatograms and absorption spectra with an
      authentic compound. The MQ-4 content was estimated to be two molecules per one
      molecule of chlorophyll (Chl) a', a constituent of P700. Comparative genomic
      analyses showed that six of eight men genes, encoding phylloquinone/MQ
      biosynthetic enzymes, are missing from the G. violaceus genome. Since G.
      violaceus clearly synthesizes MQ-4, the combined results indicate that this
      cyanobacterium must have a novel pathway for the synthesis of 1,4-dihydroxy-2
      naphthoic acid.

PMID- 15955531
TI  - Cross-talk between the TGFbeta and Wnt signaling pathways in murine embryonic
      maxillary mesenchymal cells.
AB  - The transforming growth factor beta (TGFbeta) and Wnt signaling pathways play
      central roles regulating embryogenesis and maintaining adult tissue homeostasis.
      TGFbeta mediates its cellular effects through types I and II cell surface
      receptors coupled to the nucleocytoplasmic Smad proteins. Wnt signals via binding
      to a cell surface receptor, Frizzled, which in turn activates intracellular
      Dishevelled, ultimately leading to stabilization and nuclear translocation of
      beta-catenin. Previous studies have demonstrated several points of cross-talk
      between the TGFbeta and Wnt signaling pathways. In yeast two-hybrid and GST-pull
      down assays, Dishevelled-1 and Smad 3 have been shown to physically interact
      through the C-terminal one-half of Dishevelled-1 and the MH2 domain of Smad 3.
      The current study demonstrates that co-treatment of murine embryonic maxillary
      mesenchyme (MEMM) cells with Wnt-3a and TGFbeta leads to enhanced reporter
      activity from TOPflash, a Wnt-responsive reporter plasmid. Transcriptional
      cooperation between TGFbeta and Wnt did not require the presence of a Smad
      binding element, nor did it occur when a TGFbeta-responsive reporter plasmid
      (p3TP-lux) was transfected. Overexpression of Smad 3 further enhanced the
      cooperation between Wnt and TGFbeta while overexpression of dominant-negative
      Smads 2 and 3 inhibited this effect. Co-stimulation with TGFbeta led to greater
      nuclear translocation of beta-catenin, providing explanation for the effect of
      TGFbeta on Wnt-3a reporter activity. Wnt-3a exerted antiproliferative activity in
      MEMM cells, similar to that exerted by TGFbeta. In addition, Wnt-3a and TGFbeta
      in combination led to synergistic decreases in MEMM cell proliferation. These
      data demonstrate a functional interaction between the TGFbeta and Wnt signaling
      pathways and suggest that Wnt activation of the canonical pathway is an important
      mediator of MEMM cell growth.

PMID- 15955533
TI  - Multiple variants of the ING1 and ING2 tumor suppressors are differentially
      expressed and thyroid hormone-responsive in Xenopus laevis.
AB  - The tumor suppressor candidate, inhibitor of growth (ING) is implicated in the
      control of apoptosis, cell cycle progression, chemosensitivity, and senescence.
      There are at least five different genes in mammals, ING1-ING5, and there is
      limited evidence that multiple transcript variants exist for ING1 that encode
      proteins with different functions. No variants have yet been reported for other
      ING genes. Here, we report the isolation of seven Xenopus laevis (x)ING1 and
      three xING2 transcript variants and give the first evidence for their independent
      regulation by thyroid hormone (TH). Comparison with mammalian genes reveals
      conservation in gene structure. xING1 and xING2 transcript variants are
      differentially expressed in adult tissues with the greatest number of variants
      expressed at high levels in brain, testis, and eye. During metamorphosis of the
      tadpole into a frog, the hindlimb, tail, and brain undergo growth, apoptosis, or
      remodeling, respectively. We show that xING1 and xING2 transcript variants are
      significantly reduced in the hindlimb while many variants increase in the tail.
      These transcript variants remain largely unchanged in the brain during this
      developmental period. By exposing premetamorphic tadpoles to TH, a precocious
      metamorphosis is induced. We identify specific variants whose steady state levels
      are significantly affected by TH at 24 and 48h of exposure. Although several of
      the variants show expression patterns reminiscent of that observed in natural
      metamorphosis, the results indicate that additional factors may be involved to
      influence the steady state transcript levels during development.

PMID- 15955534
TI  - Effect of 20-hydroxyecdysone on cannibalism, sexual behavior, and contact sex
      pheromone in the solitary female spider, Tegenaria atrica.
AB  - We investigated the effect of exogenously administered 20-hydroxyecdysone (20E)
      on sexual behavior and on contact sex signals of adult females of the spider
      Tegenaria atrica. In untreated or control females cannibalism occurred in 36-47%
      of encounters, whereas no cannibalism at all was observed with 20E-treated
      females. The frequency of sexual receptivity was low (42%) in untreated or
      control females and high (100%) in 20E-treated females. Variability of female
      sexual behavior could be related to quantitative changes in web and cuticular
      compounds. We showed that 20E altered the production of polar contact sex
      pheromones on web and cuticle: methylesters and fatty acids are produced in
      higher amounts in 20E-treated females. Bioassays demonstrated clearly that
      methylesters and fatty acids of webs and cuticles were involved in attraction of
      males. Moreover, bioassays with synthetic substances showed that four fatty acids
      (myristic, pentadecanoic, hexadecanoic, and oleic acids) and one methylester
      (methyl stearate) are particularly effective in eliciting sexual behavior in
      males. In T. atrica, 20E inhibits cannibalism during sexual activity and changes
      sex pheromone production.

PMID- 15955535
TI  - Hormonal and experiential control of female-male mounting in the female rat.
AB  - Mounting behavior in the female rat has been studied extensively in same-sex
      interactions, but not in the heterosexual dyad. The present study examined the
      display of female mounting of castrated noncopulating male rats (FMM).
      Ovariectomized (OVX) sexually naive female rats (N = 80) were given either
      estrogen (E) + progesterone (P), E + oil (O), P + O, or O + O treatment for five
      tests with castrated male rats. FMMs were observed in both the E + P and E + O
      females. The influence of the ovarian cycle on FMM was also investigated. Vaginal
      smears from sexually naive females (N = 16) were taken daily for 12 days
      immediately after testing with castrated males. FMM frequency was greatest during
      Proestrus. Finally, OVX females (N = 30) treated with E + P were given either 0,
      1, 10 multi-ejaculatory heterosexual experiences with intact, sexually
      experienced males, prior to tests with intact, copulating or castrated,
      noncopulating males for five tests. Sexually naive females displayed a greater
      number of mounts relative to the sexually experienced females when tested with
      castrated, noncopulating males. In contrast, very few FMMs were observed in
      females of any group tested with intact, copulating males. These data suggest
      that FMM occurs naturally in rats as a "super-solicitational" behavior that is
      modified by hormone treatment and prior heterosexual experience.

PMID- 15955536
TI  - Predictions of summer diapause in the redlegged earth mite, Halotydeus destructor
      (Acari: Penthaleidae), in Australia.
AB  - A prediction for the onset of a summer diapause in the eggs of the redlegged
      earth mite, Halotydeus destructor, was developed for Australia. In this species
      diapause eggs pass the summer in the cadavers of adult female mites. Adult female
      mites were collected for several weeks from pastures in spring at 18 sites in
      south-western Australia and dissected to determine the timing of the production
      of diapause eggs. Some sites were sampled for several years between 1990 and
      1997. A model was developed to predict the time for onset of diapause. The week
      at which 90% of eggs were in diapause was predicted best by daylength (80.1% of
      the variability), then by duration of the long-term plant growing season (10.4%,
      of variability), leaving 9.5% due to other factors. A single chemical spray in
      spring 2 weeks before the production of 90% diapause eggs resulted in 99% fewer
      mites present in autumn 7-8 months later at three sites. The timing of the spring
      spray was the factor leading to successful control. This model was tested at 17
      sites across the whole geographical distribution of the redlegged earth mite in
      Australia between 1998 and 2001. The observed week of 90% diapause was within 1
      week of the predicted week on 81% of occasions, and 2 weeks earlier on 15% of
      occasions. A database was created for the predicted date of onset of 90% diapause
      for the whole distribution of the redlegged earth mite in southern Australia on a
      10 km(2) grid. Australian farmers are using this for timing a spring spray to
      control mites in the following autumn.

PMID- 15955537
TI  - The effects of acclimation on thermal tolerance, desiccation resistance and
      metabolic rate in Chirodica chalcoptera (Coleoptera: Chrysomelidae).
AB  - Despite much focus on species responses to environmental variation through space
      and time, many higher taxa and geographic areas remain poorly studied. We report
      the effects of temperature acclimation on thermal tolerance, desiccation rate and
      metabolic rate for adult Chirodica chalcoptera (Coleoptera: Chrysomelidae)
      collected from Protea nerifolia inflorescences in the Fynbos Biome in South
      Africa. After 7 days of acclimation at 12, 19 and 25 degrees C, critical thermal
      maxima (mean+/-s.e.: 41.8+/-0.2 degrees C in field-fresh beetles) showed less
      response (<1 degrees C change) to temperature acclimation than did the onset of
      the critical thermal minima (0.1+/-0.2, 1.0+/-0.2 and 2.3+/-0.2 degrees C,
      respectively). Freezing was lethal in C. chalcoptera (field-fresh SCP -14.6
      degrees C) and these beetles also showed pre-freeze mortality. Survival of 2 h at
      -10.1 degrees C increased from 20% to 76% after a 2 h pre-exposure to -2 degrees
      C, indicating rapid cold hardening. Metabolic rate, measured at 25 degrees C and
      adjusted by ANCOVA for mass variation, did not differ between males and females
      (2.772+/-0.471 and 2.517+/-0.560 ml CO2 h(-1), respectively), but was higher in
      25 degrees C-acclimated beetles relative to the field-fresh and 12 degrees C
      acclimated beetles. Body water content and desiccation rate did not differ
      between males and females and did not respond significantly to acclimation. We
      place these data in the context of measured inflorescence and ambient
      temperatures, and predict that climate change for the region could have effects
      on this species, in turn possibly affecting local ecosystem functioning.

PMID- 15955538
TI  - Role of the isoprenoid pathway in ras transforming activity, cytoskeleton
      organization, cell proliferation and apoptosis.
AB  - The isoprenoid pathway, by its end-products lipids, has an important role in the
      control of ras transforming activity, cytoskeleton organization, cell
      proliferation and apoptosis. In particular, prenylation, a post-translational
      addition of farnesol and geranylgeraniol, is an important event for the
      biological activity of many proteins that play critical roles in signal
      transduction and cytoskeletal regulation, as well as in cell proliferation and
      apoptosis. We have been interested in studying the: (a) regulation of the
      isoprenoid pathway in the processing of cellular transformation induced by the K
      ras oncogene, (b) role of the isoprenoid pathway in the control of cell
      proliferation and apoptosis, (c) role of the isoprenoid pathway in the control of
      cytoskeleton organization and (d) control of Rab expression by the isoprenoid
      pathway.

PMID- 15955539
TI  - A double dissociation between sensitivity to changes in object identity and
      object orientation in the ventral and dorsal visual streams: a human fMRI study.
AB  - We used an event-related fMR-adaptation paradigm to investigate changes in BOLD
      activity in the dorsal and ventral visual streams as a function of object
      identity and object orientation. Participants viewed successive paired images of
      real-world, graspable objects, separated by a visual mask. The second image of
      each pair was either: (i) the same as the first image, (ii) different only in
      identity, (iii) different only in orientation, or (iv) different in both identity
      and orientation. A region in the parieto-occipital cortex (dorsal stream) showed
      a selective increase in BOLD activity with changes in object orientation, but was
      insensitive to changes in object identity. In contrast, a region in the temporo
      occipital cortex (ventral stream) showed a selective increase in activity with
      changes in identity, but was insensitive to changes in orientation. The
      differential sensitivity to orientation and identity is consistent with the idea
      that the dorsal stream plays a critical role in the visual control of object
      directed actions while the ventral stream plays a critical role in object
      perception.

PMID- 15955540
TI  - Corpus callosum size correlates with asymmetric performance on a dichotic
      listening task in healthy aging but not in Alzheimer's disease.
AB  - Alzheimer's disease (AD) involves not only gray matter but also white matter
      pathology, as reflected by atrophy of the corpus callosum (CC). Since decreased
      CC size may indicate reduced functional interhemispheric connectivity,
      differences in callosal size may have cognitive consequences that may become
      specifically apparent in neuropsychological tasks that tap hemispheric
      laterality. In the present study, we examined callosal functioning with a
      dichotic listening task in 25 Alzheimer patients, 20 healthy elderly and 20
      healthy elderly with subjective memory complaints. We found decreased
      performance, increased ear asymmetry, and decreased callosal size in the AD group
      compared to healthy elderly. As expected, in the healthy elderly, we found
      significant negative correlations between ear asymmetry and callosal size,
      specifically in the anterior and posterior callosal subareas. While the
      association with the posterior subareas (isthmus and splenium) points at
      involvement of temporal areas mediating language processing, the association with
      the anterior subarea (the rostrum and genu) points at involvement of frontal
      areas mediating attention and executive functions. Remarkably however, in
      contrast to the healthy elderly, callosal size was not related to ear asymmetry
      in the AD group. The absence of an association between callosal atrophy and ear
      asymmetry implies that other pathological processes, next to reduced callosal
      functioning, attribute to ear asymmetry in AD. Difficulties to attend
      specifically to the left ear during dichotic listening in some of the AD
      patients, points at decreased attention and executive functions and suggests that
      pathology of specifically the frontal areas is involved.

PMID- 15955541
TI  - A benzoisofuranone derivative and carbazole alkaloids from Murraya koenigii and
      their antimicrobial activity.
AB  - A benzoisofuranone derivative, 3xi-(1xi-hydroxyethyl)-7-hydroxy-1
      isobenzofuranone, and a dimeric carbazole alkaloid, 3,3'-[oxybis(methylene)]bis(9
      methoxy-9H-carbazole), along with six known carbazole alkaloids and three known
      steroids were isolated from the stem bark of Murraya koenigii. The structures of
      these compounds were established unambiguously by UV, IR, MS and a series of 1D
      and 2D NMR analyses. The minimum inhibitory concentrations (MIC) of these
      compounds were found to be in the range 3.13-100 microg/ml.

PMID- 15955542
TI  - Hemlock alkaloids from Socrates to poison aloes.
AB  - Hemlock (Conium maculatum L. Umbelliferae) has long been known as a poisonous
      plant. Toxicity is due to a group of piperidine alkaloids of which the
      representative members are coniine and gamma-coniceine. The latter is the more
      toxic and is the first formed biosynthetically. Its levels in relation to coniine
      vary widely according to environmental conditions and to provenance of the
      plants. Surprisingly, these piperidine alkaloids have turned up in quite
      unrelated species in the monocotyledons as well as the dicotyledons. Aloes, for
      instance, important medicinal plants, are not regarded as poisonous although some
      species are very bitter. Nevertheless a small number of mostly local species
      contain the alkaloids, especially gamma-coniceine and there have been records of
      human poisoning. The compounds are recognized by their characteristic mousy
      smell. Both acute and chronic symptoms have been described. The compounds are
      neurotoxins and death results from respiratory failure, recalling the effects of
      curare. Chronic non-lethal ingestion by pregnant livestock leads to foetal
      malformation. Both acute and chronic toxicity are seen with stock in damp meadows
      and have been recorded as problems especially in North America. The alkaloids
      derive biosynthetically from acetate units via the polyketide pathway in contrast
      to other piperidine alkaloids which derive from lysine.

PMID- 15955543
TI  - Assignment of avian reovirus temperature-sensitive mutant recombination groups B,
      C, and D to genome segments.
AB  - We recently generated a new set of avian orthoreovirus (ARV) temperature
      sensitive (ts) mutants after chemical mutagenesis of wild-type strain ARV138 and
      described mutants in the A recombination group. Here, each prototype ts mutant
      from ARV recombination groups B, C, and D was crossed with wild-type ARV strain
      176 to generate reassortant clones that were used to map the ts lesions in the
      respective mutants. Reassortant clones were identified by comparison of segment
      mobility to parental markers in polyacrylamide gels. An efficiency of plating
      (EOP) value, which measures the capacity of a virus clone to grow under non
      permissive conditions, was used to assign reassortant clones to either a ts group
      or non-ts group. Analysis of EOP values and parental origin of genome segments in
      the reassortant clones revealed that the group B lesion in tsB31 was located on
      the M2 genome segment; the group C lesion in tsC37 was on the S3 genome segment;
      and the group D lesion in tsD46 was on the L2 genome segment. The assignments of
      tsB31 and tsC37 were further confirmed by sequence analysis and amino acid
      substitutions in the corresponding muB and sigmaB proteins localized within the
      recently determined homologous mammalian reovirus mu1/sigma3 heterohexameric
      crystal structure.

PMID- 15955544
TI  - In situ bioremediation of a cis-dichloroethylene-contaminated aquifer utilizing
      methane-rich groundwater from an uncontaminated aquifer.
AB  - At a trichloroethylene (TCE)-contaminated site in Chikura, Chiba, Japan, TCE had
      spread over to the first and second aquifers over years. After 8 years of pumping
      and treatment, finally derivative of TCE, cis-dichloroethylene (c-DCE) remained
      only in the second aquifer. In this study, feasibility of a low cost in situ
      bioremediation utilizing groundwater of the third aquifer, which contained
      natural dissolved methane possibly derived from natural gas field nearby, to
      stimulate methane-oxidizing bacteria was examined. In vitro experiment showed
      that a mixture of the groundwater from the second and third aquifers stimulated a
      growth of methane oxidizing bacteria and enhanced c-DCE degradation. The
      groundwater of the third aquifer was introduced into the second aquifer in situ.
      The population of methanotrophs with high V(max) and K(m) for methane uptake
      increased, resulting in successful degradation of c-DCE at a monitoring well 2m
      downgradient of the injection well.

PMID- 15955545
TI  - Vertical distribution of sediment enzyme activities involved in the cycling of
      carbon, nitrogen, phosphorus and sulphur in three boreal rural lakes.
AB  - Vertical distribution of eleven hydrolytic enzyme activities were investigated
      with fluorogenic model substrates in boreal rural lake sediments, Lake Uurainen
      (13 km(2)), Lake Jamijarvi (9 km(2)) and Lake Pyylampi (0.068 km(2)), in Finland.
      The eleven hydrolytic enzyme activities were high into deep sediment layers
      indicating potential for turnover of organic matter in the permanently anoxic
      zones. The activities of beta-glucosidase, sulphatase and N-acetyl
      glucosaminidase were similar in the three lakes independent on the ecological
      status of the lake. Acetate- and butyrate-esterase were more active than the
      other enzymes in the three lakes. These unspecific esterases had sediment
      activities in forest Lake Pyylampi close to those reported for boreal coniferous
      forest soils in Finland. Similar beta-cellobiosidase activities throughout the
      sediment depths indicated constant depolymerisation potential for cellulose.

PMID- 15955546
TI  - Glycation, ageing and carnosine: are carnivorous diets beneficial?
AB  - Non-enzymic protein glycosylation (glycation) plays important roles in ageing and
      in diabetes and its secondary complications. Dietary constituents may play
      important roles in accelerating or suppressing glycation. It is suggested that
      carnivorous diets contain a potential anti-glycating agent, carnosine (beta
      alanyl-histidine), whilst vegetarians may lack intake of the dipeptide. The
      possible beneficial effects of carnosine and related structures on protein
      carbonyl stress, AGE formation, secondary diabetic complications and age-related
      neuropathology are discussed.

PMID- 15955547
TI  - Protein methionine content and MDA-lysine adducts are inversely related to
      maximum life span in the heart of mammals.
AB  - Aging affects all organisms and its basic mechanisms are expected to be conserved
      across species. Oxidation of proteins has been proposed to be one of the basic
      mechanisms linking oxygen radicals with the basic aging process. If oxidative
      damage to proteins is involved in aging, long-lived animals (which age slowly)
      should show lower levels of markers of this kind of damage than short-lived ones.
      However, this possibility has not been investigated yet. In this study, steady
      state levels of markers of different kinds of protein damage--oxidation (glutamic
      and aminoadipic semialdehydes), mixed glyco- and lipoxidation (carboxymethyl- and
      carboxyethyllysine), lipoxidation (malondialdehydelysine) and amino acid
      composition--were measured in the heart of eight mammalian species ranging in
      maximum life span (MLSP) from 3.5 to 46 years. Oxidation markers were directly
      correlated with MLSP across species. Mixed glyco- and lipoxidation markers did
      not correlate with MLSP. However, the lipoxidation marker malondialdehydelysine
      was inversely correlated with MLSP (r2=0.85; P<0.001). The amino acid
      compositional analysis revealed that methionine is the only amino acid strongly
      correlated MLSP and that such correlation is negative (r2=0.93; P<0.001). This
      trait may contribute to lower steady-state levels of oxidized methionine residues
      in cellular proteins. These results reinforce the notion that high longevity in
      homeothermic vertebrates is achieved in part by constitutively decreasing the
      sensitivity of both tissue proteins and lipids to oxidative damage. This is
      obtained by modifying the constituent structural components of proteins and
      lipids, selecting those less sensitive to oxidative modifications.

PMID- 15955548
TI  - Copper and zinc concentrations in serum of healthy Greek adults.
AB  - Serum copper and zinc concentrations of 506 (414 males and 92 females) apparently
      healthy Greek blood donors aged 18-60 years old were determined by flame atomic
      absorption spectrometry. The mean copper and zinc concentrations were 115.46+/
      23.56 microg/dl and 77.11+/-17.67 microg/dl, respectively. The mean value for
      copper and zinc in females was higher than in males, although the difference for
      zinc was smaller than the one observed for copper. When the subjects were divided
      into various age groups there appeared to be some increase in copper
      concentration as a function of age, whereas zinc concentration did not change.
      There were no significant variations in serum copper and zinc concentrations due
      to place of residence, occupation and socioeconomic status. This study is the
      first one evaluating the serum status of copper and zinc in healthy Greeks and it
      has shown that they are at the highest concentration range for copper and the
      lowest for zinc compared to literature data on copper and zinc levels for various
      countries.

PMID- 15955549
TI  - 8-OH-DPAT-induced effects on prepulse inhibition: pre- vs. post-synaptic 5-HT1A
      receptor activation.
AB  - Prepulse inhibition (PPI) is a measure of sensorimotor gating that is deficient
      in schizophrenia. In rats, administration of the serotonin-1A (5-HT1A) receptor
      agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), causes a disruption
      of PPI. It is unclear whether this effect is due to the activation of pre- or
      post-synaptic 5-HT1A receptors, however pre-synaptic receptors located in the
      dorsal raphe nucleus (DRN) may play a role. Our previous research showed that
      castrated rats have a reduced sensitivity to 8-OH-DPAT-induced disruptions of
      PPI. Therefore, in , male Sprague-Dawley rats were sham-operated or castrated and
      micro-injected with 8-OH-DPAT directly into the DRN. In , male rats were sham
      operated or received a selective serotonergic, 5,7-dihydroxytryptamine lesion of
      the DRN. 8-OH-DPAT was injected subcutaneously in these rats. In both sham
      operated and castrated rats, a micro-injection of 8-OH-DPAT into the DRN did not
      disrupt PPI. Instead, in castrated rats, 8-OH-DPAT treatment tended to increase
      PPI. A DRN lesion caused a significant reduction in 5-HT content in the frontal
      cortex (70% reduction), striatum (69%) and ventral hippocampus (76%). In both
      sham-operated and DRN-lesioned rats, systemic 8-OH-DPAT significantly disrupted
      PPI. Taken together, these data suggest that the disruption of PPI observed in
      rats with systemic 8-OH-DPAT treatment is predominantly due to an activation of
      post-synaptic, rather than pre-synaptic, 5-HT1A receptors.

PMID- 15955550
TI  - Influence of vedaprofen (Quadrisol) on quality and freezability of stallion
      semen.
AB  - The objective of this study was to evaluate the effect of the non-steroidal anti
      inflammatory drug (NSAID) vedaprofen (Quadrisol) on quality and freezability of
      stallion semen. Experiments were performed using 22 Franches Montagnes stallions
      from the National Stud in Avenches (Switzerland) randomly divided into a control
      and test group. Vedaprofen was given orally to all stallions of the test group at
      the recommended therapeutic dose (initial dose of 2mg/kg followed by 1mg/kg body
      weight every 12h) for 14 days. Control animals received the same amount of
      carrier substance. During treatment, blood samples of five stallions in both test
      and control group were collected for PGF(2 alpha)-metabolite (PG-metabolite)
      determination. Ejaculates from all stallions were collected and cryopreserved
      weekly for 14 weeks from September to December. Concentrations of PG-metabolite,
      PGF and PGE were measured in the seminal plasma of ejaculates collected 2 weeks
      before, during and 2 weeks after treatment. In fresh semen the volume,
      concentration, motility and number of normal sperm and sperm with major defects
      (acrosome defects, abnormal heads, nuclear vacuoles, proximal droplets, midpiece
      defects) were evaluated. In frozen-thawed semen samples motility as well as
      viability (SYBR-14/PI) were tested and the hypoosmotic swelling test (HOS) was
      performed. Results demonstrate that vedaprofen had no effect on blood plasma
      concentration of PG-metabolite but significantly inhibited both, PGF and PGE
      concentrations in seminal plasma. Furthermore, all quality parameters in fresh
      and frozen-thawed semen were not affected by vedaprofen treatment but the time of
      semen collection had a significant (P<0.05) effect on motility, normal sperm and
      sperm with nuclear vacuoles in fresh semen.

PMID- 15955551
TI  - Theoretical aspects of canine semen cryopreservation.
AB  - Changes in canine sperm cells during freezing and thawing can cause damage to the
      cells resulting in cell death. No standardized freezing or thawing method appears
      to be ideal for all dogs and all ejaculates, because intrinsic variations in
      properties such as osmotic sensitivity between sperm cells from different dogs
      and ejaculates makes the cellular response to cryopreservation unpredictable
      according to the normal physics of cryobiology. Research in canine semen
      cryopreservation is difficult because the low ejaculate volume makes multiple
      comparisons from a single ejaculate difficult. True fertility data is also very
      limited on cryopreserved canine ejaculates. Despite this, the cottage industry
      that has evolved to cryopreserve dog sperm has been very successful using
      empirically derived methods that accommodate most ejaculates. Therefore, the
      practitioner must follow the recommendations supplied by the freezing center to
      achieve the best potential results.

PMID- 15955553
TI  - Welfare aspects of theriogenology: investigating alternatives to
      electroejaculation of bulls.
AB  - Evaluation of the breeding soundness of bulls is an important management tool.
      Electroejaculation has been a reliable method of obtaining a semen sample for the
      purpose of evaluating breeding soundness, but is considered by some to be
      inhumane on the grounds that it is painful. This paper provides a review of
      studies conducted to find ways to both measure, as well as lessen, pain
      associated with electroejaculation, and to explore alternatives to
      electroejaculation in bulls. Changes in heart rate, serum cortisol, serum
      progesterone, relative aversion, and degrees of vocalization, struggling and
      lying down have been used to assess the pain associated with electroejaculation.
      Transrectal massage and artificial vaginas, and oxytocin and cloprostenol have
      been investigated as alternatives to, and facilitators of electroejaculation,
      respectively. Epidural, intravenous and topical anesthetics have been used to
      ameliorate the pain associated with electroejaculation. Serum progesterone and
      degrees of vocalization are useful for measuring the pain associated with
      electroejaculation in bulls. Transrectal massage and artificial vaginas are not
      as efficacious as electroejaculation for obtaining a semen sample and drugs used
      to facilitate or decrease pain associated with electroejaculation have not been
      efficacious enough to warrant use. Transrectal massage of the ampullae may be of
      some use as an alternative to electroejaculation in docile bulls and may be also
      be used to decrease the duration of subsequent electroejaculation. Pain
      associated with electroejaculation may be influenced by operator technique;
      therefore, operators of electroejaculator equipment must strive to apply
      electrical stimulation as gently as possible.

PMID- 15955552
TI  - Normal calves produced after transfer of in vitro fertilized embryos cultured
      with an antiviral compound.
AB  - Bovine viral diarrhea virus (BVDV) replicates in embryo co-culture systems and
      remains associated with developing IVF bovine embryos, despite washing and
      trypsin treatment. Previous research demonstrated that 2-(4-[2
      imidazolinyl]phenyl)-5-(4-methoxyphenyl)furan (DB606) inhibits replication of
      BVDV in cultured cells. The objective of this study was to evaluate the
      capability of IVF embryos to develop into normal, weaned calves after exposure to
      antiviral concentrations of DB606 during IVC. Oocytes were obtained from cows via
      transvaginal, ultrasound-guided follicular aspiration. Presumptive zygotes (n =
      849) that resulted from fertilization of these oocytes were cultured for 7 d in
      medium supplemented with 0.4 microM DB606 or medium lacking antiviral agent. All
      blastocysts (n = 110) were transferred individually into the uterus of a
      synchronized recipient. The pregnancy status of recipients was determined using
      transrectal ultrasonography at 21-23 d after embryo transfer. Additional
      pregnancies as controls (n = 21) were initiated by natural breeding. Developing
      fetuses and resulting calves were evaluated every 27-34 d. Blastocyst
      development, pregnancies per transferred embryo, pregnancies maintained per
      pregnancies established, gestation length, gender ratio, birth weights, viability
      of neonates, complete blood counts, and serum chemistry profiles at 3 mo of age
      and adjusted 205 d weaning weights were compared for research treatments.
      Development to weaning after exposure to DB606 did not differ significantly from
      controls. In conclusion, bovine embryo cultures can be safely supplemented with
      antiviral concentrations of DB606; addition of DB606 agent might prevent viral
      transmission if BVDV were inadvertently introduced into the embryo culture
      system.

PMID- 15955554
TI  - Compatibility of lyotropic liquid crystals with viruses and mammalian cells that
      support the replication of viruses.
AB  - We report a study that investigates the biocompatibility of materials that form
      lyotropic liquid crystals (LCs) with viruses and mammalian cells that support the
      replication of viruses. This study is focused on aqueous solutions of
      tetradecyldimethyl-amineoxide (C(14)AO) and decanol (D), or disodium cromoglycate
      (DSCG; C(23)H(14)O(11)Na(2)), which can form optically birefringent, liquid
      crystalline phases. The influence of these materials on the ability of vesicular
      stomatitis virus (VSV) to infect human epitheloid cervical carcinoma (HeLa) cells
      was examined by two approaches. First, VSV was dispersed in aqueous C(14)AO+ D or
      DSCG, and then HeLa cells were inoculated by contacting the cells with the
      aqueous C(14)AO + D or DSCG containing VSV. The infectivity of VSV to the HeLa
      cells was subsequently determined. Second, VSV was incubated in LC phases of
      either C(14)AO + D or DSCG for 4 h, and the concentration (titer) of infectious
      virus in the LC was determined by dilution into cell culture medium and
      subsequent inoculation of HeLa cells. Using these approaches, we found that the
      LC containing C(14)AO + D caused inactivation of virus as well as cell death. In
      contrast, we determined that VSV retained its infectivity in the presence of
      aqueous DSCG, and that greater than 74-82% of the HeLa cells survived contact
      with aqueous DSCG (depending on concentration of DSCG). Because VSV maintained
      its function (and we infer structure) in LCs formed from DSCG, we further
      explored the influence of the virus on the ordering of the LC. Whereas the LC
      formed from DSCG was uniformly aligned on surfaces prepared from self-assembled
      monolayers (SAMs) of HS(CH(2))(11)(OCH(2)CH(2))(4)OH on obliquely deposited films
      of gold in the absence of VSV, the introduction of 10(7)-10(8) infectious virus
      particles per milliliter caused the LC to assume a non-uniform orientation and a
      colorful appearance that was readily distinguished from the uniformly aligned
      LCs. Control experiments using cell lysates with equivalent protein
      concentrations but no virus did not perturb the uniform alignment of the LC.

PMID- 15955555
TI  - Surface charge and the effect of excess calcium ions on the hydroxyapatite
      surface.
AB  - This paper describes the use of surface titration as a more direct probe of the
      surface chemistry of hydroxyapatite (HA) than zeta-potential measurements. The
      variation in HA surface charge with pH for two different KCl electrolyte
      concentrations was determined titrimetrically and the point of zero charge (PZC)
      found to be at a pH of 7.3 +/- 0.1. The curves also demonstrated that HA
      accumulates positive charge more readily below the PZC than it accumulates
      negative charge above it. Extended titration data indicated that dissolution
      occurred more rapidly in increasingly acidic conditions, but was inhibited by
      increasing electrolyte strength. Similar experiments with 2.5 mM Ca(2+) in the
      electrolyte show that Ca(2+) adsorption balances loss of H(+) to give a near
      neutral surface at any pH above 7 (subject to availability of calcium ions and
      adsorption sites). The mechanism for adsorption has been shown to be
      deprotonation of adjacent surface HPO(4)(2-) sites and subsequent adsorption of a
      calcium ion to the lattice surface site. Furthermore, inhibition of dissolution
      under alkaline conditions in the presence of Ca(2+) suggested that dissolution
      was driven by desorption of Ca(2+). Modelling of the adsorption/desorption
      processes demonstrated that in both pure water and under physiological conditions
      phosphate groups will predominate at the HA surface. Furthermore, the (200) plane
      was identified as the likely form of the HA surface. These methodologies and
      findings are particularly relevant to investigation of biological response with
      respect to modification of surface hydrophobicity and surface energy or charge.

PMID- 15955556
TI  - Tuning the sol-gel microenvironment for acetylcholinesterase encapsulation.
AB  - The effect of the sol-gel microenvironment on the activity of
      acetylcholinesterase, an enzyme of high bio-analytical interest, is presented and
      is correlated to the overall analytical performance of corresponding biosensors.
      The sol-gel membranes are initially optimized with respect to the catalyst and
      the TEOS:H2O ratio (r), for mechanical stability, porosity, and hydrophobicity as
      well as in terms of enzymatic activity. FT-IR and electrochemical impedance
      spectroscopy (EIS) are used to probe the configuration and rotational mobility of
      the enzyme within the sol-gel matrices. Overall, it is observed that the
      rotational mobility of the protein can be correlated with the sensitivity of the
      biosensor. Optimum biosensor performance is obtained for base-catalyzed sol-gels
      with r values close to 2. The biosensor has sensitivity of 2.5 microA/mm, a
      linear range of response between 1 and 3mm, response time of about 30s, and
      sensor-to-sensor reproducibility (RSD) of 3%. These analytical characteristics
      are far superior to previously reported sol-gel biosensors.

PMID- 15955557
TI  - Chlorhexidine-releasing methacrylate dental composite materials.
AB  - Light curable antibacterial, dental composite restoration materials, consisting
      of 80 wt% of a strontium fluoroaluminosilicate glass dispersed in methacrylate
      monomers have been produced. The monomers contained 40-100 wt% of a 10 wt%
      chlorhexidine diacetate (CHXA) in hydroxyethylmethacrylate (HEMA) solution and 60
      0 wt% of a 50/50 mix of urethane dimethacrylate (UDMA) and triethyleneglycol
      dimethacrylate (TEGDMA). On raising HEMA content, light cure polymerisation rates
      decreased. Conversely, water sorption induced swelling and rates of diffusion
      controlled CHXA release from the set materials increased. Experimental composites
      with 50 and 90 wt% of the CHXA in HEMA solution in the monomer were shown, within
      a constant depth film fermentor (CDFF), to have slower rates of biofilm growth on
      their surfaces between 1 and 7 days than the commercial dental composite Z250 or
      fluoride-releasing dental cements, Fuji II LC and Fuji IX. When an excavated
      bovine dentine cylinder re-filled with Z250 was placed for 10 weeks in the CDFF,
      both bacteria and polymers from the artificial saliva penetrated between the
      material and dentine. With the 50 wt% experimental HEMA/CHXA formulation, this
      bacterial microleakage was substantially reduced. Polymer leakage, however, still
      occurred. Both polymer and bacterial microleakage were prevented with a 90 wt%
      HEMA/CHXA restoration in the bovine dentine due to swelling compensation for
      polymerisation shrinkage in combination with antibacterial release.

PMID- 15955558
TI  - Characteristics of Poly-L-Ornithine-coated alginate microcapsules.
AB  - Poly-L-Lysine (PLL) is the most widely used biomaterial for providing perm
      selectivity in alginate microcapsules for islet transplantation. We had
      previously reported that Poly-L-Ornithine (PLO) is less immunogenic than PLL, and
      in the present study, we have compared the physical characteristics of PLO- and
      PLL-coated hollow alginate microcapsules. Microspheres made with 1.5% alginate
      were divided into 2 groups that were first coated with either 0.1% PLO or PLL,
      followed by a second coating with 0.25% alginate. After liquefaction of the inner
      alginate core with sodium citrate, the microcapsules were washed with saline and
      used for experiments. Pore size exclusion studies were performed with FITC
      labeled lectins incubated with encapsulated pig islets followed by examination
      for fluorescence activity. Mechanical strength was assessed by an osmotic
      pressure test and by 36 h of mechanical agitation of microcapsules with inert
      soda lime beads. The pore size exclusion limit of microcapsules after 20 min of
      coating was significantly smaller with PLO. While the mean +/- SEM diameter of
      PLL-coated microcapsules increased from 718+/-17 to 821 +/- 17 microm (p < 0.05)
      during 14 days incubation at 37 degrees C, the PLO group did not change in size.
      Also, PLL group had a higher percentage of broken capsules (52.7 +/- 4.9%)
      compared to 3.1 +/- 2.05% for PLO capsules (p < 0.0001,n = 6). We conclude that
      PLO-coated alginate microcapsules are mechanically stronger and provide better
      perm-selectivity than PLL-coated microcapsules.

PMID- 15955559
TI  - Expression of von Hippel Lindau (pVHL) protein in placentae from normal pregnant
      women and women with preeclampsia.
AB  - The hypoxia inducible transcription factors, HIF-1alpha and -2alpha proteins, are
      overexpressed in placentae from women with preeclampsia (Biol Reprod 2001;64:499
      506; Biol Reprod 2001;64:1019-1020). Normally, these proteins are regulated in an
      oxygen-dependent manner being rapidly degraded by the ubiquitin-mediated
      proteasomal pathway. Recent studies have shown that the tumor suppressor protein,
      von Hippel Lindau (VHL), targets HIF for ubiquitinylation under nonhypoxic
      conditions. The objectives of the present work were: (1) to investigate VHL
      protein expression in normal pregnant (NP), preeclamptic (PE), and preterm
      (without PE) placentae, (2) to test whether VHL protein is hypoxia inducible in
      term and first trimester placental villous explants, and (3) to analyze the
      ontogeny of VHL protein expression in the human placenta. To begin evaluating the
      potential contribution of VHL to HIF overexpression in preeclamptic placentae, we
      analyzed the levels of the VHL protein in both normal and preeclamptic placentae
      (n=7 each). We hypothesized a deficiency of VHL protein in preeclamptic
      placentae. Eight biopsy sites were tested in each placenta and protein extracts
      were made. Western analysis was performed using VHL specific antibodies. Human
      renal adenocarcinoma (ACHN) cell extracts and extracts from COS-7 cells
      transfected with a VHL expression vector were used as positive controls. In a
      total of 112 biopsy sites that were analyzed (56 each for normal and preeclamptic
      placentae), the composite densitometry ratios (PE/NP) for the long (28 kDa) and
      short (19 kDa) forms of VHL were 1.09+/-0.2 and 1.16+/-0.11, respectively (both
      p=NS vs 1.0). A ratio of 1.0 indicates equal expression by preeclamptic and
      normal placentae. The same placentae exhibited composite densitometry (PE/NP)
      ratios of 1.97+/-0.23 and 1.68+/-0.20 for HIF-1alpha and -2alpha proteins,
      respectively (both p<0.05 vs 1.0). In a separate analysis, the protein expression
      of the short form of VHL was also comparable among NP, PE and preterm (n=6)
      placentae. VHL immunoreactivity was localized to cells within the basal plate and
      the syncytiotrophoblast. Despite induction of HIF proteins by hypoxia in first
      and term villous explants, there was no significant upregulation of VHL proteins.
      Finally, the expression of both the short and long forms of VHL protein decreased
      with gestational age (both p<0.05 by ANOVA), and in villous tissue from first
      trimester placentae VHL immunoreactivity was predominantly localized to the
      cytotrophoblast. These results suggest that (1) deficiency of VHL protein does
      not account for HIF-alpha overexpression in preeclamptic placentae, (2) VHL
      protein is not regulated by hypoxia in either first trimester or term placental
      villous explants, and (3) VHL protein expression in the placenta decreases as a
      function of gestational age.

PMID- 15955560
TI  - Expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors TGF-betaRI and
      TGF-betaRII in placentomes of artificially inseminated and nuclear transfer
      derived bovine pregnancies.
AB  - Bovine nuclear transfer pregnancies are characterized by a high incidence of
      placental abnormalities, notably, increased placentome size and deficiencies in
      trophoblast cell function and establishment of placental vasculature. Alterations
      in gene expression during placental growth and development may contribute to the
      appearance of large placentomes in pregnancies derived from nuclear transfer. The
      placenta synthesizes a number of cytokines and growth factors, including the
      transforming growth factor-betas (TGF-betas) that are involved in the
      establishment, maintenance and/or regulation of pregnancy. All forms of TGF-beta
      and their receptors are present at the fetal-maternal interface of the bovine
      placentome, where they are thought to play an important role in regulating
      growth, differentiation, and function of the placenta. Using real-time RT-PCR, we
      have examined the expression of TGF-beta1, TGF-beta2, TGF-beta3 and the receptors
      TGF-betaRI and TGF-betaRII in placentomes of artificially inseminated (AI) and
      nuclear transfer (NT)-derived bovine pregnancies at days 50, 100 and 150 of
      gestation. TGF-beta1, TGF-beta2 and TGF-beta3 mRNA expression increased by 2.0
      2.8-fold, while TGF-betaRI and TGF-betaRII mRNA expression decreased by 1.7-2.0
      fold in NT placentomes compared to AI controls at all gestational ages examined.
      These findings indicate that NT placentomes may be resistant to the growth
      suppressive effects of TGF-betas and could contribute to the placental
      proliferative abnormalities observed in NT-derived placentas. Alternatively,
      deficiencies in placentation may provide a mechanism whereby TGF-betas are
      dysregulated in NT pregnancies.

PMID- 15955561
TI  - Rapamycin and FK506 reduce skeletal muscle voltage sensor expression and
      function.
AB  - FK506 and rapamycin are immunosuppressant drugs that disrupt the interaction of
      FK506-binding proteins (FKBPs) with ryanodine receptors (RyR1), which form
      homotetrameric Ca2+ release channels in the sarcoplasmic reticulum (SR) of
      skeletal muscle. Here, we characterized the effects of short-term treatment (2 h)
      of skeletal myotubes with either 20 microM FK506 or 20 microM rapamycin on
      excitation-contraction (EC) coupling, sarcolemmal dihydropyridine receptor (DHPR)
      function, resting intracellular Ca2+, and levels of SR Ca2+ content. Both
      rapamycin and FK506 produced remarkably similar effects. Specifically, both drugs
      reduced the maximal amplitude of voltage-gated SR Ca2+ release ((DeltaF/F)max) by
      70-75% in parallel with a 50% reduction in both maximal immobilization resistant
      charge movement (Qmax) and L-type Ca2+ channel conductance (Gmax). Neither
      immunosupressant significantly altered steady-state levels of either resting
      myoplasmic Ca2+ or SR Ca2+ content. Thus, store depletion does not account for
      the observed reduction in Ca2+ release during EC coupling. Instead, the
      inhibitory effect on voltage-gated SR Ca2+ release is explained by significant
      reductions in both the number of functional sarcolemmal voltage sensors and the
      intrinsic gain of voltage-gated Ca2+ release (i.e. the maximal rate of Ca2+
      release per unit gating charge).

PMID- 15955562
TI  - Status and outlook of ecological soil classification and assessment concepts.
AB  - This article provides an outlook for the further development of ecological soil
      classification and assessment systems, based on the insights of an international
      group of authors working on the development of such systems for their respective
      governments. It is shown that a lot may be learned from the assessment of the
      quality of aquatic ecosystems. Parallel to the approach applied there, an
      approach based on extensive monitoring and ecological insights is proposed for
      soils. The article also contains recommendations for research to be done to
      derive optimal terrestrial monitoring networks, derivation of descriptions of
      reference locations, derivation of ecological quality criteria, the development
      of indicators, and an optimal exchange of data.

PMID- 15955563
TI  - Differential regulation of dendritic cell-T cell cross talk in the gut-associated
      lymphoid tissue.
AB  - Dendritic cells (DC) play a central role in the regulation of immune responses by
      processing and presenting antigens to naive T cells. It has been proposed that
      after the initial interaction between DC and T cells, T cell-induced DC apoptosis
      serves as a down-regulatory mechanism that prevents the otherwise continuous
      activation of T cells by antigen-bearing DC. Our aim was to investigate and
      compare the susceptibility of Peyer's patch (PP)-derived and systemic (splenic)
      DC to antigen-specific T cell-mediated apoptosis in mice of different genetic
      background. Freshly isolated CD11c(+/hi)B220(-) DC from intestinal Peyer's patch
      and spleen from Balb/c and C3H/HeJ mice were co-cultured with syngeneic antigen
      specific T cells in the presence or absence of the relevant antigen. In both
      mouse strains PP-DC showed higher susceptibility to T cell-mediated apoptosis
      compared to splenic ones, but levels of DC apoptosis were overall higher in
      C3H/HeJ mice compared to Balb/c. DC apoptosis was induced by both Th1 and Th2
      antigen-specific clones and was strictly MHC class II-dependent in both strains,
      and interestingly we observed that although CD95-CD95L ligation played an overall
      minor part in T cell-induced DC apoptosis its role varied according to the mouse
      strain. Here, we demonstrated that PP-DC and splenic DC significantly differed in
      regard to their susceptibility to T cell-mediated killing. We interpreted these
      data as showing that the reciprocal regulation between DC and T cells in the
      gastrointestinal immune system is under stricter control compared to the systemic
      immune system and we hypothesized that these events are likely to contribute to
      the generation of fine balanced responses to intestinal antigens.

PMID- 15955564
TI  - Cloning and characterization of the human CD200 promoter region.
AB  - CD200 is a type I membrane glycoprotein which is expressed on a number of cell
      types uniquely relevant to the inflammatory and immune cascade; included in those
      are dendritic cells, endothelial cells and activated T cells. Previous studies
      have shown that CD200 plays an important role in prevention of graft rejection,
      autoimmune diseases and spontaneous abortion. The molecular mechanism(s)
      controlling expression of CD200 are yet to be defined. We report below the
      cloning and characterization of the 5'-flanking region of the human CD200 gene,
      including an exon1/intron1 boundary region and various transcriptional initiation
      sites. Serial deletion analysis revealed a 169 bp region responsible for
      constitutive expression of CD200. Positive regulatory domains (PRDs) were
      identified in the core promoter using linker-scanning mutagenesis. EMSA
      documented clear evidence for C/EBPbeta as being important in transcriptional
      regulation of CD200.

PMID- 15955565
TI  - The platelet P2 receptors as molecular targets for old and new antiplatelet
      drugs.
AB  - Platelet activation by ADP and ATP plays a crucial role in haemostasis and
      thrombosis, and their so-called P2 receptors are potential targets for
      antithrombotic drugs. The ATP-gated channel P2X1 and the 2 G protein-coupled P2Y1
      and P2Y12 ADP receptors selectively contribute to platelet aggregation. The P2Y1
      receptor is responsible for ADP-induced shape change and weak and transient
      aggregation, while the P2Y12 receptor is responsible for the completion and
      amplification of the response to ADP and to all platelet agonists, including
      thromboxane A2 (TXA2), thrombin, and collagen. The P2X1 receptor is involved in
      platelet shape change and in activation by collagen under shear conditions. Due
      to its central role in the formation and stabilization of a thrombus, the P2Y12
      receptor is a well-established target of antithrombotic drugs like ticlopidine or
      clopidogrel, which have proved efficacy in many clinical trials and experimental
      models of thrombosis. Competitive P2Y12 antagonists have also been shown to be
      effective in experimental thrombosis as well as in several clinical trials.
      Studies in P2Y1 and P2X1 knockout mice and experimental thrombosis models using
      selective P2Y1 and P2X1 antagonists have shown that, depending on the conditions,
      these receptors could also be potential targets for new antithrombotic drugs.

PMID- 15955566
TI  - Immunostimulatory DNA activates production of type I interferons and interleukin
      6 in equine peripheral blood mononuclear cells in vitro.
AB  - This study aimed to evaluate different nucleic acid preparations as cytokine
      inducers in equine cells. To induce cytokine production, bacterial plasmid DNA or
      short synthetic oligodeoxyribonucleotides (ODN), with or without the transfection
      reagent lipofectin, were added to cultures of purified equine peripheral blood
      mononuclear cells (PBMC). Cytokine activity was detected with bioassays in cell
      culture supernatants after 24h of induction and cytokine mRNA expression was
      detected using RT-PCR at 6h post induction. For IFN-alpha/beta it was found that
      both plasmid DNA and phosphodiester ODN, containing an unmethylated CpG-motif,
      were able to induce IFN production in the presence of lipofectin but not without.
      The levels of IFN varied with individuals and were often quite low. Moreover,
      methylation or removal of the CpG sequence completely abolished IFN induction.
      CpG-containing ODN with poly-guanine (G) sequences in the 5' and 3' ends induced
      considerably higher levels of IFN, especially when the poly-G sequences had a
      phosphorothioate backbone. ODN with poly-G sequences also had the ability to
      induce IFN in the absence of lipofectin but the levels of IFN induced were
      radically reduced compared to those induced with lipofectin. In contrast to IFN,
      which was only detected upon induction, low spontaneous IL-6 production was
      observed in unstimulated control cultures. Nevertheless, plasmid DNA and CpG
      containing ODN were able to increase the IL-6 production threefold. All the IFN
      inducing ODN also induced IL-6 production and the levels of IL-6 induced seemed
      influenced by addition of lipofectin and presence of poly-G sequences in the same
      way as was observed for the IFN-production. However, a complete phosphorothioate
      ODN with a central CpG-motif and poly-C sequences, that did not induce IFN,
      readily induced IL-6 both in the presence and absence of lipofectin. In addition,
      there was also evidence that some ODN induced increased expression of IL-12p40
      mRNA. To conclude, equine PBMC were able to recognize CpG-DNA and respond with
      both IFN-alpha/beta and/or IL-6 production. The levels of cytokine induced, and
      sometimes which cytokine induced, varied with, e.g., CpG-motifs used, the
      presence of poly-G sequences, ODN backbone chemistry and presence of lipofectin.

PMID- 15955567
TI  - Thermal injury and sepsis modulates beta-adrenergic receptors and cAMP responses
      in monocyte-committed bone marrow cells.
AB  - We have previously reported that adrenergic stimulation enhances monocytopoiesis
      following experimental burn injury and sepsis (BI/S). In the present work we
      measured beta-adrenergic receptor number and affinity in bone marrow committed
      monocyte progenitor cells (CD59(+)) following BI/S. We find that BI/S treatment
      significantly decreased monocyte progenitor cell beta-adrenergic receptors but
      significantly increased receptor binding affinity and isoproterenol-stimulated
      cAMP production. CD14 expression in macrophages derived in vitro from CD59(+)
      cells following BI/S was significantly increased by epinephrine and this change
      was blocked by beta(2)-adrenergic receptor antagonist. PCR analysis suggests the
      presence of beta(2)- but not beta(1)-adrenergic receptors. Enhanced adrenergic
      receptor signaling in CD59(+) bone marrow cells following BI/S may be important
      in macrophage development.

PMID- 15955568
TI  - Acoustic rhinometric measurements in children undergoing rapid maxillary
      expansion.
AB  - OBJECTIVE: To evaluate geometric changes of nasal cavities in children undergoing
      rapid maxillary expansion and to assess the effect of this procedure on nasal
      airway size by means of acoustic rhinometry. METHOD: We recruited 14 mouth
      breather children (mean age 8.2 years) presenting constricted maxillary arches
      and scheduled for rapid maxillary expansion in the orthodontics department of our
      hospital. Clinical history did not reveal any allergic diseases and ENT
      examination was completely normal with a well-aligned nasal septum. Nasal
      measurements were obtained using acoustic rhinometry, which was performed before
      the expansion treatment and after 1-year follow-up. A postero-anterior radiograph
      of the skull was also performed in all patients for cephalometric analysis before
      and 3 months after the treatment. RESULTS: We observed a satisfactory increment
      in the transverse dimension of the maxilla in all patients but one who manifested
      a relapse after 4 months from the treatment and required a second procedure.
      Similarly, acoustic rhinometric measurements and cephalometric tracings showed a
      statistically significant increase respectively in decongested total nasal
      volumes (p=0.047) and in binasal cavity width (p=0.001). However, only eight
      children switched their respiration from oral to nasal breathing mode.
      CONCLUSIONS: Rapid maxillary expansion is an effective method for increasing the
      width of narrow maxillary vault and it is also associated with a significant
      increment in nasal volumes and in the transverse diameter of the maxilla. With
      regard to breathing posture, the role of this procedure still remains debatable.
      To date this is the first study aimed at analysing the effects of rapid maxillary
      expansion on nasal dimensions by means of acoustic rhinometry.

PMID- 15955569
TI  - Management of parapharyngeal minor salivary neoplasms in children: a case report
      and review.
AB  - Parapharyngeal neoplasms are rare entities in children. Benign minor salivary
      gland neoplasms of the parapharyngeal space have been described in the adult
      literature, but there is little guidance in the pediatric literature. We present
      the case of an adolescent male with a primary minor salivary gland pleomorphic
      adenoma presenting as an enlarging, asymptomatic parapharyngeal mass. We discuss
      the clinical presentation, radiologic findings, differential diagnosis and our
      surgical management with a summary of the current literature on the topic.

PMID- 15955570
TI  - Intractable pulmonary aspiration in children: which operation?
AB  - Intractable aspiration is a life-threatening medical problem. There are many
      surgical procedures for the treatment of intractable aspiration. Our experience
      with three children was reported here. After failing initial conservative
      measures, the first two patients had supraglottic laryngeal closure performed
      through an endoscopic approach with a small hole left superiorly for phonation.
      However, both of them developed dehiscence of the closure postoperatively,
      necessitating a more definitive procedure to stop the aspiration. Their symptoms
      of aspiration were only relieved after they underwent laryngotracheal separation.
      In the third child, laryngotracheal separation was performed as the initial
      procedure and the symptoms of recurrent aspiration were relieved. In conclusion,
      the treatment of intractable aspiration requires a definitive procedure from the
      outset and we would suggest, based on literature review and on our experience,
      that laryngotracheal separation is the most effective and reliable option, albeit
      lack of phonation is inevitable. A comprehensive review of all procedures used
      for treatment of this condition was also undertaken.

PMID- 15955571
TI  - Unusual aero-digestive foreign bodies: tribulations and tragedies.
AB  - Aero-digestive foreign bodies are a common occurrence in infants and children.
      The manifestations, hazards and consequences depend upon the location, nature of
      the foreign body and the time lapse. This communication reports a series of four
      cases with unusual course and consequences of aero-digestive foreign bodies.
      These were generalized tetanus, hypernatremia and metabolic acidosis with intra
      cranial hemorrhage and severe pneumonia and empyema. Awareness of these
      consequences would help treating doctors to take appropriate steps in devising
      preventive and therapeutic strategies.

PMID- 15955572
TI  - Speech perception of children using Nucleus, Clarion or Med-El cochlear implants.
AB  - OBJECTIVE: The purpose of this study was to present speech perception
      achievements of implanted children using commercially available cochlear implant
      devices: Nucleus, Clarion or Med-El. STUDY DESIGN: A retrospective analysis.
      METHODS: Speech perception data of 96 hearing-impaired children: 27 with Clarion,
      49 with Nucleus and 20 with Med-El were collected. Speech tests included the
      Hebrew Infant Toddlers Meaningful Auditory Integration Scale (HIT-MAIS) for the
      infants, the Hebrew Early Speech Perception (HESP) closed-set word-identification
      test and Hebrew Arthur Boothroyd (HAB) open-set one-syllable word recognition
      test were used for the older children. RESULTS: I HIT-MAIS: (1) Infants showed
      similar rate of progress, regardless of device. (2) Children implanted under two
      years of age reached performance within normal development on this test. II HAB:
      (1) Most children achieved open set results with mean HAB between 40 and 50%,
      within 1-1.5 years post implantation. (2) Linear regression analyses revealed no
      statistical differences between the Clarion the Nucleus and the Med-El devices on
      the mean final measurement of this test. (3) Age of implantation and mode of
      communication were significant covariate variables: (a) the younger the child is
      implanted the better the results and (b) oral communication prior to implantation
      results in better performance than sign language. CONCLUSIONS: There are no
      apparent differences in speech perception performance between implant devices
      when considering background variables. The data have important implications on
      the rehabilitation process of hearing impaired children with cochlear implants in
      relation to device selection, age at implantation and mode of communication prior
      to implantation.

PMID- 15955573
TI  - Acute otitis media-diagnosis and treatment in the era of antibiotic resistant
      organisms: updated clinical practice guidelines.
AB  - The treatment of children with AOM has to rely on an accurate diagnosis and a
      clear discrimination between AOM and serous otitis media. The last decade has
      seen major changes in the epidemiology of AOM with an earlier onset of disease
      and a greater proportion of children with recurrent/complicated AOM. The
      processes of changing susceptibility of bacterial pathogens added a major problem
      in treatment selection. Tastier, more efficient, safe and conveniently-dosing as
      well as cost effective drugs are required to achieve adherence to therapy. The
      recent published guidelines for the treatment of AOM in the present era of
      pneumoccocal resistance represent a major step forward in the approach to the
      management of this disease by establishing a clear hierarchy among the various
      therapeutic agents. A 48-72 h observation option without use of antibacterial
      therapy in selected children with uncomplicated AOM should be promoted.
      Immunization against S. pneumoniae with the heptavalent pneumococcal conjugated
      vaccines was showed to result in a decrease in the frequency of AOM caused by
      this pathogen, including AOM caused by antibiotic-resistant S. pneumoniae.

PMID- 15955574
TI  - Lingual cyst lined by squamous epithelium.
AB  - Lingual choristomas or foregut duplication cysts are infrequently reported
      congenital anomalies that typically present in the perinatal period, and can
      cause respiratory or feeding problems. These cysts are lined by epithelial cells
      characteristic of the upper aerodigestive tract. We describe two children who
      presented shortly after birth with lingual cysts lined with squamous epithelium
      and foci of respiratory epithelium. Unlike previously reported lingual
      choristomas, these cysts did not contain gastrointestinal epithelium. In both
      these cases, the lingual cysts were successfully excised via a transoral
      approach. This article will discuss the histological findings in these two cases,
      the differential diagnosis and attempt to classify these lesions in the context
      of existing terminology.

PMID- 15955575
TI  - Hearing and speech assessment of cleft palate patients after palatal closure.
      Long-term results.
AB  - OBJECTIVE: The goal of this study was the development of a clinical methodology
      to assess speech and hearing impairment 5 years after the primary surgical repair
      of the cleft and, further, to determine the relative importance and long-term
      consequences of each cleft type and age to the velopharyngeal and eustachian tube
      function in patients who did not undergo pharyngeal flap surgery following
      primary palatoplasty. MATERIALS AND METHODS: We evaluated with a certain
      assessment protocol hearing and speech abilities of 42 patients between 5 and 15
      years of age: 9 with CP (cleft of the soft and hard palate), 19 with unilateral
      cleft lip and palate (UCLP), 14 with bilateral cleft lip and palate (BCLP),
      surgically treated by a team of surgeons using two different surgical techniques
      between 18 and 24 months of age. ACCORDING TO OUR RESULTS WE WERE ABLE TO
      EVALUATE: (a) the impact of hearing impairment to the development of speech in
      these patients. (b) The relation of hypernasality with compansatory articulation.
      (c) The influence of cleft type, by means of extent of the cleft palatal
      musculature, to speech integrity. RESULTS: Sixty-nine percent of our patients
      presented with mild and moderate hearing loss. Hypernasality was observed in
      40.5%, compensatory articulation in 28.5% of our patients. CONCLUSIONS: Our
      findings indicated: (a) a simultaneous appearance of speech and hearing
      impairment at the same age for each cleft type post-surgically in our patients;
      (b) that the muscular and vomer complex rather than the anatomic extent of the
      cleft is a significant factor for speech outcome after surgical repair; and (c)
      that hypernasality is exacerbated by compensatory articulation.

PMID- 15955576
TI  - Rapid human metapneumovirus microneutralization assay based on green fluorescent
      protein expression.
AB  - We describe a simple and expedited microneutralization assay for human
      metapneumovirus virus (HMPV) based on a recombinant HMPV expressing the enhanced
      green fluorescent protein (rHMPV-GFP). Test serum dilutions were incubated with
      fixed amounts of rHMPV-GFP and inoculated onto Vero cells, and the growth of non
      neutralized rHMPV-GFP was visualized by fluorescent microscopy of living cells. A
      preliminary titer could be determined following 3 days of incubation. GFP
      expression was sufficient to be read by an automated scanner after 4-5 days of
      incubation, which also provided a permanent record. In comparison, the
      conventional serum neutralization assay requires a longer incubation time plus
      the additional steps of fixation and staining or immunostaining. rHMPV-GFP-based
      titers could be determined by the 50% infectivity endpoint method of Reed and
      Muench [Reed, L.J., Muench, H., 1938. A simple method of estimating fifty per
      cent endpoint. Am. J. Hyg. 27, 493-497], or by automated scanning and non-linear
      regression to determine the 50% endpoint of GFP fluorescence. The latter method
      was two- to three-fold more sensitive. This assay also permits automation and up
      scaling, making it suitable for broad HMPV seroepidemiology studies and
      experiments that require large scale serology, such as vaccine studies.

PMID- 15955578
TI  - Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential
      roles of dardarin.
AB  - The past decade has been a fruitful one for geneticists involved in Parkinson's
      disease (PD) research. The initial hurdle of identifying the first gene
      underlying parkinsonism was cleared with apparent ease in 1997 and four
      additional genes have since been found to contain mutations causing this
      disorder. Driving this research is the belief that these data will highlight
      disease mechanisms and directly implicate a pathway amenable to therapeutic
      intervention. This article will focus on recent genetic advances in the field,
      focusing on data that suggest alpha-synuclein expression is key in the etiology
      of PD. In addition, it will discuss the recent identification of LRRK2 mutation
      as a cause of PD and the potential of this finding to provide further insight
      into disease.

PMID- 15955577
TI  - Retinoic acid induction of ES-cell-derived neurons: the radial glia connection.
AB  - Neuronal induction by retinoic acid (RA) is commonly used in embryonic stem (ES)
      cell differentiation. Two recent papers show that this paradigm induces a
      population of neurogenic precursors with properties of radial glia. Upon
      differentiation, RA-treated cells give rise to a defined and developmentally
      restricted neuronal lineage. This role of RA in cell fate specification provides
      new perspectives for studying the radial glia-neuron transition and for
      generating homogenous populations of neurons from ES cells.

PMID- 15955579
TI  - Acclimation to Cu in fathead minnows: does age influence the response?
AB  - This study had two primary objectives. The first was to determine if the length
      of exposure necessary for acclimation to Cu to develop in larval fathead minnows
      (Pimephales promelas) is different than that for juveniles. The second objective
      was to determine whether the acclimatory response, as determined by organism
      survival, is consistent with acclimation as determined by whole-body Na+. Six
      experiments were conducted: four using larval (<20-d-old) and two using juvenile
      (<60-d-old) fathead minnows. Within each experiment, fish were allocated to one
      of four groups: unexposed, continuously exposed, episodically exposed or naively
      exposed. The continuous group was exposed to a sublethal Cu exposure (125
      microg/L) for 8, 12, 16 or 20 d and then subjected to a survival test at a lethal
      dose (375 microg/L). Fish in the episodic group were exposed to the sublethal
      dose for either 4 or 8 d, given a depuration period of varying lengths (4-16 d)
      then subjected to a survival test. Naive minnows were maintained in clean water
      then given the survival challenge. Results from survival tests show that the
      larvae acclimate after only a 4-d sublethal exposure to Cu. In contrast,
      juveniles require a 16-d exposure to acclimate. Once acclimation had developed,
      there was a strong relationship between larval survival and whole-body Na+.
      Acclimated larvae maintained whole-body Na+ relative to unexposed fish, while
      unacclimated larvae did not. Interestingly, this was not the case for juveniles,
      as acclimated and unacclimated groups did not differ with respect to whole-body
      Na+ concentrations. The results of this study show that age influences the time
      course and possibly the mechanisms of acclimation in fathead minnows exposed to
      Cu.

PMID- 15955580
TI  - Purification and characterization of photosensitizing hemolytic toxin from
      harmful red tide phytoplankton, Heterocapsa circularisquama.
AB  - We have previously found that the methanol extract prepared from Heterocapsa
      circularisquama, a harmful red rid dinoflagellate, showed light-dependent
      hemolytic activity toward rabbit erythrocytes. Interestingly, the cytotoxicity of
      the extract against HeLa cells was also strictly light-dependent, and no
      significant toxic effect was observed even at very high concentration in the
      dark. In this study, the hemolytic agents present in the extract were purified by
      several chromatographic procedures. Final HPLC analysis revealed that there are
      at least two hemolytic toxins with different retention times (H2-a and H3-a),
      which have similar absorption spectra. Although H3-a fraction was contaminated by
      a trace amount of H2-a, H2-a fraction gave a single peak on a three-dimensional
      chromatogram. The results of fast atom bombardment (FAB)-mass spectrometry (MS)
      and electrospray ionization quadrupole time-of-flight (ESI Q-TOF) mass
      spectrometry analyses suggested that the molecular weight of H2-a was 566. Since
      nuclear magnetic resonance analysis indicated the presence of a pyrrole ring in
      H2-a molecule, H2-a may be a porphyrin derivative with similar structure of
      pyropheophorbide a methyl ester, a well-known photosensitizing hemolytic
      compound. However, some structural and physicochemical differences were observed
      between H2-a and pyropheophorbide a methyl ester. Since H2-a showed potent
      photosensitizing cytotoxicity toward HeLa cells in a concentration-dependent
      manner as well as hemolytic activity, H2-a may be a novel porphyrin derivative
      with photosensitizing hemolytic cytotoxicity.

PMID- 15955581
TI  - Stressed worms: responding to the post-genomics era.
AB  - Nematodes are among the most successful organisms in withstanding stress
      conditions associated with water loss, and viable individuals have been recovered
      from dry desert soils. Little is known about the biochemical and molecular events
      underpinning nematodes' physiological responses to dehydration. Post-genomics
      research in Caenorhabditis elegans may offer an opportunity to understand the
      stress response better. This review focuses on recent progress in understanding
      the molecular mechanisms of water-loss associated stress response in the model
      nematode C. elegans and in parasitic nematodes and discusses the scope for
      applying the knowledge and tools derived from a model organism for the study of
      wild, environmentally-adapted, parasitic nematodes, in the light of the emergence
      of genomics research of non-model organisms.

PMID- 15955582
TI  - Microalgae: the "self-synchronized" eukaryotes.

PMID- 15955583
TI  - P50 sensory gating: impact of high vs. low schizotypal personality and smoking
      status.
AB  - Sensory gating deficits are seen in individuals with schizophrenia and
      schizotypal disorders, yet smoking influence, regional or lateral difference
      effects are rarely assessed. We examined sensory gating in smokers and non
      smokers within university-level high and low schizotypal personality (HiS and
      LoS) groups using [Raine, A., 1991. The Schizotypal Personality Questionnaire
      (SPQ): A measure of schizotypal personality based on DSM-III-R criteria.
      Schizophr. Bull. 17, 555-564] Schizotypal Personality Questionnaire. Among 39 (18
      men; 19 smokers) right-handed undergraduates, a paired-tone paradigm (40 pairs;
      10 s ISI; 70 dB, 1000 Hz) was presented in two conditions (smokers while
      abstaining and after smoking). Sensory gating [S2(P50-N40)/S1(P50-N40)] was
      assessed at frontal, fronto-central, central, centro-parietal, and parietal
      midline and lateralized sites. Sensory gating was better at (1) midline than
      left/right hemispheric sites, and (2) fronto-central and central midline sites.
      At fronto-central/central lateral sites, (1) among non-smokers, better sensory
      gating occurred in LoS than HiS, (2) among smokers, better sensory gating
      occurred in HiS than LoS, and (3) among LoSs, smokers showed less sensory gating
      than non-smokers. No acute smoking effects emerged. Unlike schizophrenia studies,
      smoking did not impact sensory gating. Differences among smokers and non-smokers
      in LoS and HiS groups reinforce need to evaluate both smoking and schizotypal
      characteristics, as well as midline and lateral sites in anterior to posterior
      regions, in sensory gating studies.

PMID- 15955584
TI  - Application of response surface methodology to the modeling of alpha-amylase
      purification by aqueous two-phase systems.
AB  - Mathematical models concerning the purification of alpha-amylase from the
      cultivation supernatant of Bacillus subtilis in a polyethylene glycol-citrate
      aqueous two-phase system (ATP) are established with response surface methodology.
      The PEG3350, citrate and sodium chloride concentrations were selected as
      variables to evaluate the purification impact factors in aqueous two-phase
      system, including partition coefficients of alpha-amylase, total protein,
      purification factor and alpha-amylase yield. An experimental space with two-fold
      purification and over 90% yield of alpha-amylase is achieved through the
      optimized condition basing on the model. Two systems with low viscosity within
      said space were further selected to perform alpha-amylase purification and the
      experimental results coincide well with the calculation of the models, which
      indicates that the model provides a promising tool for experimental design of
      protein purification by aqueous two-phase system.

PMID- 15955585
TI  - A new innovative process to produce lactose-reduced skim milk.
AB  - The research field for applications for lactose hydrolysis has been investigated
      for some decades. Lactose intolerance, improvement for technical processing of
      solutions containing lactose and utilisation of lactose in whey are main topics
      in development of biotechnological processes. In this article, the establishment
      of a hollow fiber membrane reactor process for enzymatic lactose hydrolysis is
      reported. Mesophilic beta-galactosidases were circulated abluminally during
      luminal flow of skim milk. The main problem, microorganisms growth in the enzyme
      solution, was minimised by sterile filtration and UV irradiation. In order to
      characterise the process parameters, such as skim milk concentration, enzyme
      activity and flow rates were varied. In comparison to a batch process, enzyme
      activity could be used longer and enzyme rest into the product should not occur.
      Furthermore, the three-dimensional separation of the substrate from the enzyme
      solution minimise blocking and washing out effects, which restrict processes with
      immobilised enzymes. A conversion rate of 78.11% was achieved at a skim milk flow
      rate of 9.9l h(-1), enzyme activity of 120 Uml(-1) and a temperature of 23+/-2
      degrees C in a hollow fiber reactor with a membrane area of 4.9 m2.

PMID- 15955586
TI  - Transcription and identification of a novel envelope protein (VP124) gene of
      shrimp white spot syndrome virus.
AB  - White spot syndrome virus (WSSV) is one of the most virulent pathogens in shrimp
      culture worldwide. Combining SDS-PAGE with mass spectrometry, a novel envelope
      protein from WSSV was identified to match an open reading frame (ORF) of WSSV
      genome. This ORF contained 3582nt, encoding 1194 aa, and was termed the vp124
      gene. One part of the whole gene (named vp124p) was cloned into pET-GST vector
      and expressed as a fusion protein with glutathione S-transferase (GST) in
      Escherichia coli strain BL21 (DE3). Specific antibodies were raised using the
      purified fusion protein (GST-VP124P). Temporal transcription analysis revealed
      that the vp124 gene was a late gene. Western blot analysis showed that the mouse
      anti-GST-VP124P antibodies reacted specifically with VP124 present either in the
      WSSV virions or in the viral envelopes, and did not react with the proteins of
      the viral nucleocapsids. VP124 was located in the WSSV virions as an envelope
      protein using immunoelectron microscopy.

PMID- 15955587
TI  - Type 1 diabetes developed in a type 2 diabetic patient with severe insulin
      resistance.
AB  - We report a 38-year-old female with severe insulin resistance who developed type
      1 diabetes after being diagnosed with type 2 diabetes. At the initial
      examination, BMI was 31.8 kg/m(2) and HbA1c 10.8%. Her insulin secretion was
      sufficient (urinary CPR 80 microg/day) and the GAD antibody was negative.
      Following treatment with insulin and glimepiride, HbA1c decreased to 6.3%, though
      diabetic control deteriorated after 1 year (HbA1c, 11.0%) and her body weight was
      reduced in a short period, from 78 to 67 kg. Re-examination revealed that the GAD
      antibody was high (1870 U/mL, normal <1.5) and the anti-islet cell antibody
      positive, and insulin secretion decreased (urinary CPR 18 microg/day). Further, a
      hyperinsulinemic-euglycemic cramp study using an artificial pancreas showed that
      the patient had severe insulin resistance [glucose infusion rate 1.8 mg/(min kg);
      normal, 7.4+/-2.4 (mean+/-S.D.)]. An HLA-analysis showed that she was a
      homozygote of haplotype DRB1*0901-DQB1*0303. In spite of strict insulin therapy,
      glucose control was not improved. Pioglitazone could not be used because of side
      effects, however, metformin was effective for glucose control. The accumulation
      of case reports of patients with type 1 diabetes and insulin resistance is
      important for studying the relationship between the onset of the disease and
      insulin resistance, and for developing an effective treatment strategy.

PMID- 15955588
TI  - Postprandial hypertriglyceridemia and carotid intima-media thickness in north
      Indian type 2 diabetic subjects.
AB  - Hypertriglyceridemia is an important risk factor for coronary heart disease (CHD)
      and in the development of atherosclerosis, especially in subgroups of the
      population like those with type 2 diabetes. Although triglycerides are generally
      increased in the postprandial period, the association between postprandial
      triglyceride (ppTG) levels and atherosclerosis has not been investigated in north
      Indian type 2 diabetic subjects known to have a very high prevalence rate of
      premature CHD and insulin resistance. To investigate the role of ppTG levels in
      atherosclerosis in type 2 diabetes, we examined the correlation between ppTG
      levels and carotid intima-media thickness (IMT). Carotid IMT was determined by
      high resolution B-mode ultrasonography in 86 newly detected type 2 diabetic
      subjects (1-12 months duration) having good glycemic control (HbA(1C)<7%) and 45
      non-diabetic subjects matched according to age and body mass index (BMI). Plasma
      glucose, insulin, total cholesterol, LDL-cholesterol, HDL-cholesterol and
      triglycerides were measured after overnight fasting. Plasma insulin and glucose
      were also measured 2h and plasma triglycerides 4h after breakfast. The mean
      carotid IMT in diabetic subjects was higher than those in non-diabetic subjects
      (0.77+/-0.15 mm versus 0.53+/-0.16 mm, P<0.001). Based on the fasting and
      postprandial triglyceride levels, the diabetic subjects were divided into three
      groups: normo-normo (NN); normo-hyper (NH); hyper-hyper (HH) [NN: fTG<1.70 mmol/L
      and ppTG<2.30 mmol/L; NH: fTG<1.70 mmol/L and ppTG>2.30 mmol/L; HH: fTG>1.70
      mmol/L and ppTG>2.30 mmol/L]. Carotid IMT was significantly increased in the NH
      (0.79+/-0.09 mm) and HH (0.82+/-0.06 mm) groups compared with the NN group
      (0.59+/-0.09 mm, P<0.001). Although ppTG, age, fasting LDL-cholesterol, HOMA
      estimated insulin resistance, HbA(1C) were all independently correlated with
      carotid IMT, age and ppTG levels had the strongest statistical influence
      (P<0.002).

PMID- 15955589
TI  - Developing a healthy ageing policy for Ireland: the view from below.
AB  - There is a healthy ageing programme in a place in Ireland since 1998. However,
      there has never been a systematic review of healthy ageing policy in the country
      or of the impact of the new programme on the sector. This paper uses both a
      quantitative and qualitative survey methodology to elicit the views of
      participants and stakeholders on current policy and future priorities for healthy
      ageing in Ireland. The data are based on extensive consultation with stakeholders
      in the field of healthy ageing and adheres to a participative model of research
      in keeping with best practice in health promotion investigation. New information
      is provided on the nature and structure of healthy ageing activity in the country
      and on the major issues for stakeholders in respect of resource allocation,
      priorities and best practice. The results suggest that current policy needs to be
      recalibrated in favour of greater public support for projects in the social
      environment. Overall funding also needs to be increased for the sector and
      genuine partnerships between policy-makers and older people need to be
      established. Finally, the paper reports a worrying concern among stakeholders of
      the deleterious effect of ageism on the participation of older people at all
      levels of society.

PMID- 15955590
TI  - Content-based image database system for epilepsy.
AB  - We have designed and implemented a human brain multi-modality database system
      with content-based image management, navigation and retrieval support for
      epilepsy. The system consists of several modules including a database backbone,
      brain structure identification and localization, segmentation, registration,
      visual feature extraction, clustering/classification and query modules. Our newly
      developed anatomical landmark localization and brain structure identification
      method facilitates navigation through an image data and extracts useful
      information for segmentation, registration and query modules. The database stores
      T1-, T2-weighted and FLAIR MRI and ictal/interictal SPECT modalities with
      associated clinical data. We confine the visual feature extractors within
      anatomical structures to support semantically rich content-based procedures. The
      proposed system serves as a research tool to evaluate a vast number of hypotheses
      regarding the condition such as resection of the hippocampus with a relatively
      small volume and high average signal intensity on FLAIR. Once the database is
      populated, using data mining tools, partially invisible correlations between
      different modalities of data, modeled in database schema, can be discovered. The
      design and implementation aspects of the proposed system are the main focus of
      this paper.

PMID- 15955591
TI  - Bootstrap confidence intervals for the mode of the hazard function.
AB  - In many applications of lifetime data analysis, it is important to perform
      inferences about the mode of the hazard function in situations of lifetime data
      modeling with unimodal hazard functions. For lifetime distributions where the
      mode of the hazard function can be analytically calculated, its maximum
      likelihood estimator is easily obtained from the invariance properties of the
      maximum likelihood estimators. From the asymptotical normality of the maximum
      likelihood estimators, confidence intervals can be obtained. However, these
      results might not be very accurate for small sample sizes and/or large proportion
      of censored observations. Considering the log-logistic distribution for the
      lifetime data with shape parameter beta>1, we present and compare the accuracy of
      asymptotical confidence intervals with two confidence intervals based on
      bootstrap simulation. The alternative methodology of confidence intervals for the
      mode of the log-logistic hazard function are illustrated in three numerical
      examples.

PMID- 15955592
TI  - Stromal cell-derived factor-1 (SDF-1) gene and susceptibility of Iranian patients
      with lung cancer.
AB  - Stromal cell derived factor-1 (SDF-1), a CXC chemokine that play important roles
      in tumor growth, angiogenesis and metastasis of tumor cells, has a polymorphism
      at position 801 of its 3'-untranslated region, known as SDF1-3'A. This
      polymorphism has been investigated in HIV-1 infection and the susceptibility to
      breast cancer. In this investigation 72 lung cancer patients and 262 cases of
      normal healthy control were investigated for the genotype frequency of SDF-1
      gene. Genotype frequency was carried out by PCR-RFLP method. Of 72 cancer
      patients 9 (12.5%) cases were emerged with AA genotype, 38 (52.8%) patients with
      AG and 25 (34.7%) with GG genotype. Comparison of these data with genotype
      frequency of SDF-1 gene of 262 normal healthy controls indicates a significant
      difference among patient and control groups (P=0.008). Results also showed that
      the frequency of AA and AG genotypes was higher among patients, while the
      frequency of GG genotype was lower compared to the controls. By considering the
      importance of SDF-1 in several physiological processes and also its significant
      biological behavior in cancer metastasis and on the basis of the results of this
      study we conclude that AA and AG genotypes of SDF-1 may be considered as factors
      increasing the susceptibility of Iranian patients to lung cancer.

PMID- 15955593
TI  - Int7G24A variant of the TGFBR1 gene and cancer risk: a meta-analysis of three
      case-control studies.

PMID- 15955594
TI  - Gefitinib, an EGFR tyrosine kinase inhibitor, directly inhibits the function of P
      glycoprotein in multidrug resistant cancer cells.
AB  - Gefitinib (Iressa) is a selective epidermal growth factor receptor tyrosine
      kinase inhibitor and is used for the treatment of lung cancer. Recently, we
      discovered that it inhibits the breast cancer resistance protein, which is an ATP
      binding cassette transporter. P-glycoprotein (Pgp) also pumps multiple types of
      drugs out of the cell using energy generated from ATP, and confers multidrug
      resistance on cancer cells. This study was designed to examine whether gefitinib
      inhibits the function of Pgp. We used multidrug resistant PC-6/PTX lung cancer
      and MCF-7/Adr breast cancer cells which overexpress Pgp and measured their drug
      sensitivity and drug-efflux function by tetrazolium assay and flowcytometry,
      respectively. In addition, the drug-stimulated ATPase activity of Pgp was
      measured using insect membranes that express human Pgp. Epidermal growth factor
      receptor was expressed in MCF-7/Adr, but not in PC-6/PTX cells, and the
      overexpression of Pgp did not confer resistance to gefitinib to both cell types.
      However, clinically achievable levels of gefitinib moderately reversed the Pgp
      mediated resistance to paclitaxel and docetaxel in Pgp overexpressing cells. In
      addition, gefitinib increased the intracellular accumulation of the Pgp substrate
      rhodamine-123 in resistant cells, and activated ATPase in a preparation of pure
      Pgp-expressing membrane. These findings suggest that gefitinib directly interacts
      with Pgp and inhibits its function. Gefitinib may clinically inhibit the
      excretion of Pgp substrate drugs including anticancer agents, and its drug
      interaction should therefore be considered.

PMID- 15955595
TI  - Short acidic peptides isolated from wheat sprout chromatin and involved in the
      control of cell proliferation. Characterization by infrared spectroscopy and mass
      spectrometry.
AB  - Low molecular weight peptides were isolated from the chromatin of wheat sprouts.
      Following gel filtration the peptide fraction shows a sharp inhibiting activity
      on the growth of HeLa cancer cells. Infrared (IR) spectroscopy and mass
      spectrometry have been utilized to characterize the wheat sprout peptides in an
      attempt to recognize the peptide sequence involved in the control of cell growth.
      The quantitative presence of a peptide with MH+=572 appears proportional to the
      cell growth inhibition activity. This compound has been subjected to extensive
      mass spectrometry analysis. The automatic computational analysis of the ions of
      second, third and fourth generations indicate a peptide sequence, AcHis-Asp-Ser
      Glu-, that binds at the C-terminal a molecule of ethanolamine. Moreover, the
      results show that some sequences of the wheat sprout peptide family are present
      in the peptide fractions isolated from several other tissues, thus supporting the
      hypothesis of ubiquitous regulatory peptides.

PMID- 15955596
TI  - Expression of nicotinic receptors on primary cultures of rat astrocytes and up
      regulation of the alpha7, alpha4 and beta2 subunits in response to nanomolar
      concentrations of the beta-amyloid peptide(1-42).
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are thought to be involved in
      the pathogenesis of Alzheimer's disease (AD). Interestingly, in the brains of
      patients with this disease, losses of several subtypes of nAChRs on neurons have
      been reported, while an increase in alpha7 nAChRs was recently detected in the
      astrocytes. However, little is presently known about the expressions of
      individual subunits of nAChR on rat astrocytes in primary culture or the possible
      influence of exposure to beta-amyloid peptide (Abeta), a neuropathological
      hallmark of AD, on this expression. Thus, in the present investigation the levels
      of individual nAChR subunits on primary rat astrocytes and the possible direct
      influence of Abetas on the receptors were examined by RT-PCR, Western blotting,
      monitoring intracellular free calcium and immunohistochemistry. The alpha4,
      alpha7, beta2 and beta3 subunits and related calcium channel responses were found
      in these cells, whereas neither alpha2 nor alpha3 could be detected. Elevation in
      the levels of alpha7, alpha4 and beta2 mRNAs and proteins were observed in
      astrocytes exposed to 0.1-100nM Abeta(1-42). In contrast, incubation with 1muM
      Abeta(1-42) or Abeta(35-25) did not affect these levels. We propose that the
      enhanced expression of alpha7, alpha4 and beta2 nAChRs by astrocytes stimulated
      directly by nanomolar concentrations of Abeta(1-42) might be related to ongoing
      defensive or compensative mechanisms.

PMID- 15955598
TI  - Imipramine and citalopram facilitate amyloid precursor protein secretion in
      vitro.
AB  - Comorbid depression of Alzheimer's disease (AD) is a common mood disorder in the
      elderly and a broad spectrum of antidepressants have been used for its treatment.
      Abeta peptides and other derivatives of the amyloid precursor protein (APP) have
      been implicated as central to the pathogenesis of AD. However, the functional
      relationship of APP and its proteolytic derivatives to antidepressant therapy is
      not known. In this study, Western blotting was used to test the ability of the
      tricyclic antidepressant (TCA) imipramine or the selective serotonin reuptake
      inhibitor (SSRI) citalopram to change the release of APP and the protein kinase C
      (PKC) content. Both antidepressants increased APP secretion in primary rat
      neuronal cultures. Imipramine or citalopram enhanced the level of secreted APP by
      3.2- or 3.4-fold, respectively. Increases in PKC level were observed only after
      imipramine treatment. These in vitro data suggest that both TCA and SSRI are able
      to interfere with the APP metabolism. Imipramine promotes the non-amyloidogenic
      route of APP processing via stimulatory effects on PKC. We propose that PKC is
      not involved in the mechanism underlying the effects of citalopram on the APP
      metabolism. Since the secreted APP is not further available for the pathological
      cleavage of beta- and gamma-secretases, antidepressant medication might be
      beneficial in AD therapy.

PMID- 15955597
TI  - Distinct signaling pathways for induction of type II NOS by IFNgamma and LPS in
      BV-2 microglial cells.
AB  - Nitric oxide (NO) release upon microglial cell activation has been implicated in
      the tissue injury and cell death in many neurodegenerative diseases. Recent
      studies have indicated the ability of interferon-gamma (IFNgamma) and
      lipopolysaccharides (LPS) to independently induce type II nitric oxide synthase
      (iNOS) expression and NO production in BV-2 microglial cells. However, a detailed
      comparison between the signaling pathways activating iNOS by these two agents has
      not been accomplished. Analysis of PKC isoforms revealed mainly the presence of
      PKCdelta, iota and lambda in BV-2 cells. Although both IFNgamma and LPS could
      specifically enhance the tyrosine phosphorylation of PKCdelta, treatment with
      IFNgamma induced a steady increase of phospho-PKCdelta for up to 1h, whereas
      treatment with LPS elevated phospho-PKCdelta levels only transiently, with peak
      activity at 5 min. Rottlerin, a specific inhibitor for PKCdelta, dose-dependently
      inhibited IFNgamma- and LPS-induced NO production. Despite the common involvement
      of PKCdelta, IFNgamma- but not LPS-induced NO production involved extracellular
      signal-regulated kinases (ERK1/2) cascade and IFNgamma-induced phosphorylation of
      ERK1/2 was mediated through PKC. On the other hand, LPS- but not IFNgamma-induced
      NO production was through stimulation of NF-kappaB activation and nuclear
      translocation to interact with DNA. These results demonstrated distinct signaling
      pathways for induction of iNOS by IFNgamma and LPS in BV-2 microglial cells.

PMID- 15955600
TI  - Enhancement of cell mediated immune responses using lipid depleted lentivirus as
      immunogen: a novel approach for inducing recognition of new viral epitopes.
AB  - We tested the hypothesis that removal of viral lipids using diisopropylether can
      enhance antigenicity of SIVmac251. DIPE delipidation removed cholesterol from
      SIVmac251 without significant loss of viral protein or RNA. Mice immunized with
      the same SIV preparation but boosted with delipidated SIVmac251 exhibited
      significantly broader and higher cellular and humoral immune responses compared
      to live or AT-2-inactivated virus. As little as 1microg (total protein) of
      delipidated virus was sufficient to induce such enhanced immune responses. Thus,
      solvent treated lentivirus may provide a novel strategy to generate immune
      responses to additional viral epitopes.

PMID- 15955599
TI  - Age effect on olfactory discrimination in a non-human primate, Microcebus
      murinus.
AB  - In order to characterize age-related cognitive changes, olfactory discrimination
      was assessed in Microcebus murinus, a prosimian primate. We compared young (n =
      10) and old (n = 8) animals for individual performance on three olfactory tasks.
      Animals had to perform a detection, a transfer, and a reversal learning task
      using a go, no go conditioning procedure. No differences were observed between
      the two groups, indicating that aging is not inevitably associated with a decline
      in cognitive function. We did, however, observe two aged animals showing altered
      behavior. One animal displayed impairments in the reversal learning task, and the
      other showed impairments in both the transfer and reversal tasks. Transfer
      impairment may be due to a hippocampal alteration, whereas the perseverative
      tendency noted in the reversal task may be associated with frontal lobe
      dysfunction. Because some aged M. murinus display lesions that are pathognomonic
      of Alzheimer's disease, our observations highlight its potential utility as a
      primate model for studying cognitive deficits in relation to age and associated
      pathologies.

PMID- 15955601
TI  - Effectiveness of the B subunit of cholera toxin in potentiating immune responses
      to the recombinant hemagglutinin/adhesin domain of the gingipain Kgp from
      Porphyromonas gingivalis.
AB  - The hemagglutinin/adhesin HArep domain is present in the gingipains HRgpA and Kgp
      and in the hemagglutinin HagA of Porphyromonas gingivalis and is felt to be
      important in the virulence of this bacterium. In the present study, we determined
      the immunogenicity of recombinant HArep from the gingipain Kgp (termed Kgp
      rHArep) and the effectiveness of the B subunit of cholera toxin (CTB), compared
      to other adjuvants in potentiating a specific response to Kgp-rHArep following
      intranasal (i.n.) immunization of mice. Furthermore, we determined the
      effectiveness of anti-Kgp-rHArep antibodies in protection against P. gingivalis
      invasion of epithelial cells. Evidence is provided that Kgp-rHArep was effective
      in inducing immune responses following systemic or mucosal immunization. Kgp
      rHArep induced both a Th1- and Th2-type response following i.n. immunization.
      Immunization of mice with Kgp-rHArep and CTB, either admixed or chemically
      conjugated to the antigen, via the i.n. route, resulted in a significant
      augmentation of the systemic and mucosal immune response to Kgp-rHArep, which was
      similar to or higher than the responses seen in mice immunized with antigen and
      the other adjuvants tested. CTB and the heat-labile toxin of Escherichia coli
      potentiated a Th1- and Th2-type response to Kgp-rHArep, whereas the adjuvant
      monophosphoryl lipid A preferentially promoted a Th1-type response to the
      antigen. Furthermore, anti-Kgp-rHArep antibodies were shown to protect against P.
      gingivalis invasion of epithelial cells in an in vitro system. These results
      demonstrate the effectiveness of certain mucosal adjuvants in potentiating and in
      altering the nature of the immune response to Kgp-rHArep following i.n.
      immunization, and provide evidence for the potential usefulness of Kgp-rHArep for
      the development of a vaccine against periodontal disease.

PMID- 15955602
TI  - Atmospheric dry deposition fluxes of trace elements measured in Bursa, Turkey.
AB  - Trace element dry deposition fluxes were measured using a smooth, greased, knife
      edge surrogate surface (KSS) holding greased Mylar strips in Bursa, Turkey.
      Sampling program was conducted between October 2002 and June 2003 and 46 dry
      deposition samples were collected. The average fluxes of crustal metals (Mg, Ca,
      and Fe) were one to four orders of magnitude higher than the fluxes of
      anthropogenic metals. Trace element fluxes ranged from 3 (Cd) to 24,230 (Ca)
      microg m(-2) d(-1). The average trace element dry deposition fluxes measured in
      this study were similar to those measured in other urban areas. In addition,
      ambient air samples were also collected simultaneously with flux samples and
      concentrations of trace elements, collected with a TSP sampler, were between 0.7
      and 4900 ng m(-3) for Cd and Ca, respectively. The overall trace element dry
      deposition velocities, calculated by dividing the fluxes to the particle phase
      concentrations ranged from 2.3+/-1.7 cm s(-1) (Pb) to 11.1+/-6.4 cm s(-1) (Ni).
      These values are in good agreement with the values calculated using similar
      techniques. The anthropogenic and crustal contributions were estimated by
      employing enrichment factors (EFs) calculated relative to the average crustal
      composition. Low EFs for dry deposition samples were calculated. This is probably
      due to contamination of local dust and its important contribution to the
      collected samples.

PMID- 15955603
TI  - Efficacy and toxicity of self-polishing biocide-free antifouling paints.
AB  - The ban on harmful substances in antifouling paints requires the development of
      new antifouling strategies. Alternatives should be as effective as conventional
      paints but of lower toxicity. In the present study two commercially available,
      self-polishing antifouling paints were examined in order to get information on
      their antifouling properties and toxicological potential. Efficacy was shown in
      settlement assays with the marine barnacle species Balanus amphitrite, however,
      efficacy was related to toxic effects observed on target and non-target
      organisms. Toxicity of the paint extracts was concentration-dependent and
      differed according to the paint and the species investigated. Toxicity could at
      least partially be attributed to zinc leached from the paints. Effects of a water
      soluble paint were more pronounced in larvae of B. amphitrite, Artemia salina and
      in the green algae Dunaliella tertiolecta. Embryos of the freshwater species
      Danio rerio and Vibrio fisheri were more affected by a paint based on organic
      solvents.

PMID- 15955604
TI  - The focus group method: insights from focus group interviews on sexual health
      with adolescents.
AB  - This article concerns the manner in which group interaction during focus groups
      impacted upon the data generated in a study of adolescent sexual health. Twenty
      nine group interviews were conducted with secondary school pupils in Ireland, and
      data were subjected to a qualitative analysis. In exploring the relationship
      between method and theory generation, we begin by focusing on the ethnographic
      potential within group interviews. We propose that at times during the
      interviews, episodes of acting-out, or presenting a particular image in the
      presence of others, can be highly revealing in attempting to understand the
      normative rules embedded in the culture from which participants are drawn.
      However, we highlight a specific problem with distinguishing which parts of the
      group interview are a valid representation of group processes and which parts
      accurately reflect individuals' retrospective experiences of reality. We also
      note that at various points in the interview, focus groups have the potential to
      reveal participants' vulnerabilities. In addition, group members themselves can
      challenge one another on how aspects of their sub-culture are represented within
      the focus group, in a way that is normally beyond reach within individual
      interviews. The formation and composition of focus groups, particularly through
      the clustering of like-minded individuals, can affect the dominant views being
      expressed within specific groups. While focus groups have been noted to have an
      educational and transformative potential, we caution that they may also be a
      source of inaccurate information, placing participants at risk. Finally, the
      opportunities that focus groups offer in enabling researchers to cross-check the
      trustworthiness of data using a post-interview questionnaire are considered. We
      conclude by arguing that although far from flawless, focus groups are a valuable
      method for gathering data about health issues.

PMID- 15955605
TI  - Community-based participatory research (CBPR) in South Africa: engaging multiple
      constituents to shape the research question.
AB  - Community engagement is an on-going, arduous, and necessary process for
      developing effective health promotion programs. The challenges are amplified when
      the particular health issue or research question is not prominent in the
      consciousness of the targeted community. In this paper, we explore the community
      based participatory research (CBPR) model as a means to negotiate a mutual agenda
      between communities and researchers. The paper is focused on the (perceived) need
      for cervical cancer screening in an under-resourced community in Cape Town, South
      Africa. Cervical cancer is a significant health problem in this community and
      elsewhere in South Africa. Unlike HIV-AIDS, however, many Black South Africans
      have not been educated about cervical cancer and the importance of obtaining
      screening. Many may not consider screening a priority in their lives. Our
      research included extensive consultations and informal interviews with diverse
      community and regional stakeholders. Following these, we conducted 27 focus
      groups and 106 demographic surveys with randomly selected youth, parents, local
      health care personnel, educators and school staff. Focus group data were
      summarized and analyzed cross-sectionally. Community stakeholders were involved
      throughout this research. Our consultations, interviews, and focus group data
      were key in identifying the concerns and priorities of the community. By engaging
      community stakeholders, we developed a research framework that incorporated the
      community's concerns and priorities, and stressed the intersecting roles of
      poverty, violence, and other cultural forces in shaping community members' health
      and wellbeing. Community members helped to refocus our research from cervical
      cancer to 'cervical health,' a concept that acknowledged the impact on women's
      bodies and lives of HIV-AIDS and STDs, sexual violence, poverty, and multiple
      social problems. We conclude that the research agenda and questions in community
      based health research should not be considered immutable. They need to be open to
      negotiation, creativity, and constant reinvention.

PMID- 15955606
TI  - Contesting stigma and contested emotions: personal experience and public
      perception of specific phobias.
AB  - This paper draws on interviews with members of the United Kingdom National
      Phobics Society to explore the implications of the contested nature of specific
      phobias for their experience and perception. In common with other chronic and
      contested conditions such as Chronic Fatigue Syndrome, phobias are stigmatised
      and subjected to widespread judgmental attitudes in both medical and lay
      populations. In contrast, however, phobic experience is rarely characterised by
      difficulty in describing symptoms and obtaining a diagnosis: core fearful
      reaction to and avoidance of particular objects is usually obvious and
      uncontested. The crucial difference is that phobias are constituted by emotions
      and behaviours considered irrational and inconsequential, and it is their
      (perceived absence of) significance that raises questions and eyebrows. In other
      words, what does it matter and who cares if you happen to be scared of snakes?
      Using phobics' own words as far as possible, the paper explores the processes
      through which phobic emotions are constructed as contested, and examines phobic
      means of managing experience and perception of these emotions. It reveals that
      many respondents are resourceful and resistant, continually renegotiating their
      positioning as irrational, incapable and emotionally weak.

PMID- 15955607
TI  - The role of astroglia in Pb-exposed adult rat brain with respect to glutamate
      toxicity.
AB  - Astrocytes maintain neuronal homeostasis in brain and controlling of the released
      glutamate is one of the most important functions. Since it is suggested that
      glutamatergic component underlies lead-induced neurotoxic effects and
      simultaneously, astrocytes serve as a cellular lead (Pb) deposition site, it was
      of interest to investigate the functioning of astroglia in adult rat brain after
      short-term exposure to Pb. We examined the expression of main astrocytic
      glutamate/aspartate transporters--GLAST and GLT-1, which regulate extracellular
      glutamate concentration. Molecular evidence is provided which indicates
      overexpression of GLAST mRNA and protein. Simultaneously, decreased expression of
      GLT-1 mRNA and protein was observed, indicating that of the two glial
      transporters, GLT-1 is more susceptible to the toxic Pb effect. Protein
      expression of glutamine synthetase (GS), which converts toxic glutamate to non
      toxic glutamine, was doubly enhanced. Moreover, Na+-dependent transport of
      radioactive glutamine to astroglia-derived fraction was affected in Pb-exposed
      rats. Both the rate of accumulation and the efflux of amino acid were diminished.
      Additionally, we observed enhanced expression of glutathione-protein complexes
      after Pb treatment what suggests activation of S-glutathionylation processes. The
      results of current studies indicate that lead toxicity in adult rat brain
      activates astrocytic processes connected with the controlling of glutamate
      homeostasis. The response of astroglia is rather of neuroprotective character
      however, downexpression of GLT-1 glutamate transporter and activation of S
      glutathionylation processes lead to the question about their significance in Pb
      induced neurotoxicity.

PMID- 15955608
TI  - Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding
      protein and lactate in adult rat in vitro.
AB  - Polychlorinated biphenyls (PCBs) are persistent and bioaccumulative environmental
      toxicants. Previous studies suggested that PCBs (Aroclor 1254) induce toxic
      effects including reproductive toxicity. The present study was designed to
      investigate the impact of Aroclor 1254 on Sertoli cellular function and
      antioxidant system of adult rat in vitro. Sertoli cells were isolated from adult
      rat testes and treated with various concentrations (10(-10) to 10(-7) M) of
      Aroclor 1254 for 6, 12 and 24 h. After the treatment period, cell viability was
      assessed and the Sertoli cellular antioxidant enzymes such as superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), gamma-glutamyl
      transpeptidase (gamma-GT) and glutathione reductase (GR) and lipid peroxidation
      (LPO) were assayed. In addition, androgen binding protein (ABP) and lactate
      secretions were also quantified in Sertoli cell culture medium. Sertoli cellular
      viability and activity of antioxidant enzymes were significantly reduced in
      Aroclor 1254 (10(-10) to 10(-7) M) treatment for 6, 12 and 24 h whereas, the
      Sertoli cellular lipid peroxidation was significantly increased in a dose and
      duration dependent manner. In addition, ABP secretion diminished and lactate
      secretion was significantly elevated in the same manner. To conclude, the present
      study suggested that Aroclor 1254 disrupts Sertoli cellular metabolic functions
      such as ABP, lactate secretions and activity of antioxidant enzymes.

PMID- 15955609
TI  - The use of routine laboratory data to predict in-hospital death in medical
      admissions.
AB  - The ability to predict clinical outcomes in the early phase of a patient's
      hospital admission could facilitate the optimal use of resources, might allow
      focused surveillance of high-risk patients and might permit early therapy. We
      investigated the hypothesis that the risk of in-hospital death of general medical
      patients can be modelled using a small number of commonly used laboratory and
      administrative items available within the first few hours of hospital admission.
      Matched administrative and laboratory data from 9497 adult hospital discharges,
      with a hospital discharge specialty of general medicine, were divided into two
      subsets. The dataset was split into a single development set, Q(1) (n=2257), and
      three validation sets, Q(2), Q(3) and Q(4) (n(1)=2335, n(2)=2361, n(3)=2544).
      Hospital outcome (survival/non-survival) was obtained for all discharges. An
      outcome model was constructed from binary logistic regression of the development
      set data. The goodness-of-fit of the model for the validation sets was tested
      using receiver-operating characteristics curves (c-index) and Hosmer-Lemeshow
      statistics. Application of the model to the validation sets produced c-indices of
      0.779 (Q(2)), 0.764 (Q(3)) and 0.757 (Q(4)), respectively, indicating good
      discrimination. Hosmer-Lemeshow analysis gave chi(2)=9.43 (Q(2)), chi(2)=7.39
      (Q(3)) and chi(2)=8.00 (Q(4)) (p-values of 0.307, 0.495 and 0.433) for 8 degrees
      of freedom, indicating good calibration. The finding that the risk of hospital
      death can be predicted with routinely available data very early on after hospital
      admission has several potential uses. It raises the possibility that the
      surveillance and treatment of patients might be categorised by risk assessment
      means. Such a system might also be used to assess clinical performance, to
      evaluate the benefits of introducing acute care interventions or to investigate
      differences between acute care systems.

PMID- 15955610
TI  - Very high survival among patients defibrillated at an early stage after in
      hospital ventricular fibrillation on wards with and without monitoring
      facilities.
AB  - BACKGROUND: The association between the interval between collapse and
      defibrillation and outcome is well described in out of hospital cardiac arrest
      but not as well in in-hospital cardiac arrest. We report the outcome among
      patients who suffered an in-hospital cardiac arrest and were found in ventricular
      fibrillation (VF) with the emphasis on the delay to defibrillation. METHODS AND
      RESULTS: In patients who suffered an in-hospital cardiac arrest at Sahlgrenska
      University Hospital in Goteborg between 1994 and 2002 there were 1.570 calls for
      the rescue team of which 71% had suffered a cardiac arrest. Among cardiac arrests
      47% took place on monitored wards. The proportion of patients found in VF was 59%
      on wards with monitoring facilities and 45% on wards without (p<0.0001).
      Approximately 90% of these patients were defibrillated <or=3 min after collapse
      on monitored wards compared with 54% on non-monitored wards (p<0.0001). Among all
      patients, there was a strong relationship between the interval between collapse
      to the first defibrillation and survival to discharge from hospital (p<0.0001):
      66% were discharged alive if defibrillated <or=3 min compared with 20% if
      defibrillated >12 min. On monitored wards, the survival was 63% if defibrillated
      <or=3 min compared with 60% if defibrillated >3 min after collapse (NS). The
      corresponding values for non-monitored wards were 72% and 35%, respectively
      (p=0.0003). Cerebral function among survivors at discharge appeared to be good
      among the majority of patients both in monitored and non monitored wards.
      CONCLUSION: If patients with in hospital VF were defibrillated early in both
      monitored and non monitored wards survival to hospital discharge was high. This
      highlights the importance of being prepared for the rapid defibrillation on wards
      without monitoring facilities.

PMID- 15955611
TI  - Are US informed consent requirements driving resuscitation research overseas?
AB  - Following a 2-year federally imposed moratorium on acute resuscitation research
      due to concern regarding the inability of patients in cardiac arrest to provide
      prospective, informed consent to participate in such research, the United States
      federal government in 1996 released regulations with provisions for exemption of
      prospective informed consent in certain types of emergency research. While very
      few acute resuscitation research studies have been attempted in the United States
      since that time, such research has continued overseas. We discuss one large multi
      center, out-of-hospital trial of a device intended to improve the hemodynamics of
      cardiopulmonary resuscitation. After pilot implementation overseas, this trial
      could not be conducted in the United States, largely due to the difficulties and
      costs involved in implementing the requirements of the 1996 regulations. A recent
      European Union directive on the conduct of clinical trials may halt European
      research on patients who are unable to provide prospective, informed consent. The
      directive contains no provisions for exceptions or waiver of informed consent,
      and may hinder acute resuscitation research in Europe to an even greater degree
      than the 1996 regulations have in the United States.

PMID- 15955612
TI  - Quality of life of elderly patients after prehospital thrombolytic therapy.
AB  - We studied the long-term outcome and quality of life of elderly patients after
      prehospital thrombolysis to treat acute ST-elevation myocardial infarction. Data
      of 218 patients after prehospital thrombolytic therapy given by two physician
      staffed Helicopter Emergency Medical Service (HEMS) units were collected
      prospectively. Physical and mental status was evaluated at 4--6 months after
      discharge, and 1-year mortality was determined. Patients older than 65 years were
      compared with those younger than 65 years. There were 112 elderly and 106 younger
      patients. The elderly patients had more previous coronary events and more
      medications. Pain to therapy times between the two groups were equal (<65 years:
      108+/-93 min (range 27--500 min) versus >65 years: 108+/-70 min (20-357 min)).
      After 4--6 months, the Barthel Daily Living Index or the Beck Depression
      Inventory (BDI) (depression, if BDI >/=10) showed no differences between the two
      groups (<65 years: 99+/-5 (range 65--100) versus >65 years: 98+/-12 (10--100);
      BDI>/=10, 18% versus 9%). One-year survival was lower among the elderly (79%
      versus 93%; p=0.001). No differences in the frequency of arrhythmias,
      haemodynamic problems during thrombolysis or complications such as intracranial
      haemorrhage after thrombolysis were detected. We concluded that elderly patients
      treated with prehospital thrombolysis for acute ST-elevation myocardial
      infarction recover mentally and physically as well as younger patients.

PMID- 15955613
TI  - Mechanisms of neurotransmitter release by amphetamines: a review.
AB  - Amphetamine and substituted amphetamines, including methamphetamine,
      methylphenidate (Ritalin), methylenedioxymethamphetamine (ecstasy), and the herbs
      khat and ephedra, encompass the only widely administered class of drugs that
      predominantly release neurotransmitter, in this case principally catecholamines,
      by a non-exocytic mechanism. These drugs play important medicinal and social
      roles in many cultures, exert profound effects on mental function and behavior,
      and can produce neurodegeneration and addiction. Numerous questions remain
      regarding the unusual molecular mechanisms by which these compounds induce
      catecholamine release. We review current issues on the two apparent primary
      mechanisms--the redistribution of catecholamines from synaptic vesicles to the
      cytosol, and induction of reverse transport of transmitter through plasma
      membrane uptake carriers--and on additional drug effects that affect
      extracellular catecholamine levels, including uptake inhibition, effects on
      exocytosis, neurotransmitter synthesis, and metabolism.

PMID- 15955614
TI  - Hysterocolpectomy with colpocleisis for massive genital prolapse in women aged
      over 70 years.
AB  - OBJECTIVES: We report long-term objective and subjective outcomes after
      hysterocolpectomy in elderly patients. METHODS: We conducted a retrospective
      study of colpocleisis procedures performed between January 1, 1989 and January 1,
      1999 in patients over 70 years of age. Patient characteristics, operative data
      and objective outcome data were obtained from the patients' records. Subjective
      outcome data were obtained by a standardized telephone interview. RESULTS: During
      the 10-year study period, 30 subjects aged between 70 and 89 years (78.1 +/- 5.8,
      average +/- S.D.) with complete uterovaginal prolapse were treated by
      colpocleisis, hysterocolpectomy, suburethral plication, anterior, posterior
      colporrhaphy and high levator plication. The median operating time and median
      decrease in hemoglobin were, respectively, 79 min (range, 50-160 min) and 2.2
      mg/dl (range, 0.2-3.6 mg/dl). No intraoperative complications occurred. The
      median hospital stay was 8 days (range, 4-20 days). Objective cure, defined as
      the absence of prolapse to the hymen, was achieved in all 30 patients. Median
      office follow-up time was 7.7 months (range, 1-21 months). Symptoms of stress
      incontinence persisted in four cases (13%) and appeared de novo in two cases
      (6.6%). Median telephone follow-up was 35 +/- 48 months (range 13-161 months).
      Five of the 30 patients died during the follow-up period. Subjective cure,
      defined as a response of "satisfied" or "very satisfied", was achieved in 25
      patients (83%). Eighty-eight percent of patients reported being very satisfied or
      satisfied. CONCLUSION: Colpocleisis with colpohysterectomy appears to be an
      effective treatment for massive uterogenital prolapse in elderly women.

PMID- 15955615
TI  - The distribution of intra-twin birth weight discordance and its association with
      total twin birth weight, gestational age, and neonatal mortality.
AB  - OBJECTIVE: To determine an appropriate cutoff value to differentiate physiologic
      and pathologic birth weight discordance, to determine the prevalence of birth
      weight discordance > or =25% among twin pregnancies in different sub-populations,
      and to examine its clinical significance. STUDY DESIGN: Historical cohort study
      of 147,262 twin sets registered in the United States between 1995 and 1997.
      RESULTS: The prevalence of birth weight discordance > or =25% among twin
      pregnancies was 8.6%. The prevalence of birth weight discordance > or =25% was
      significantly decreased with increasing total twin birth weight deciles, was more
      frequently found in twins with discordant gender (9.1%) than in those twins with
      concordant gender (8.3%) and in mothers whose age was 30 years or older (9.1%)
      than those of younger mothers (8.1%). Birth weight discordance > or =25% was
      associated with earlier gestational age at delivery (35.0 weeks versus 36.0
      weeks) and higher neonatal mortality (5.4% versus 2.3%) as compared to twins with
      lower birth weight discordance. CONCLUSIONS: The prevalence of birth weight
      discordance > or =25% among twin pregnancies was 8.6%, which is associated with
      lower gestational age at delivery and higher neonatal mortality rates, and may
      represent a pathologic process.

PMID- 15955616
TI  - The effects of hormone therapy, estrogen therapy and tibolone on apoptosis and
      cyclin D1 expression in postmenopausal vaginal epithelium.
AB  - OBJECTIVE: To investigate the effects of hormone therapy, estrogen therapy and
      tibolone on markers of apoptosis including bcl-2, and bax and cyclin D(1)
      expression in postmenopausal vaginal epithelium. STUDY DESIGN: Thirty
      postmenopausal women were randomized to the treatment protocols (0.625 mg
      conjugated equine estrogen (CEE) + 2.5 mg medroxyprogesterone acetate (MPA); 2mg
      estradiol valerate; 2.5mg tibolone). After baseline vaginal biopsy, control
      biopsies were performed after 70 days following the initiation of the therapy.
      Bcl-2, bax, Bcl-2/bax ratio, cyclin D(1) measurements were performed
      immunohistochemically. Data were analyzed by Kruskal-Wallis, Mann-Whitney U and
      Wilcoxon tests. RESULTS: After the treatment period the above-mentioned
      parameters were not different among the groups except for cyclin D(1) levels.
      Cyclin D(1) expression was found to be strong in patients with treated estradiol
      valerate. CONCLUSIONS: The effects of estrogen on cyclin D(1) expression were not
      detected with tibolone or with the addition of progesterone to estrogen in the
      vaginal epithelium. Cyclin D(1) appeared to have stronger effects on the estrogen
      related proliferation compared to apoptotic markers in vaginal epithelial cells.

PMID- 15955617
TI  - Outcomes of labours augmented with oxytocin.
AB  - OBJECTIVE: To highlight the differences in mode of delivery between women
      augmented with intravenous oxytocin because of failure to progress in labour with
      those who labour without the need for augmentation. STUDY DESIGN: An incidence
      study over a 5-year-period in a tertiary referral hospital comparing 1097
      nulliparous women who were augmented in labour with 2745 nulliparous women who
      did not need augmentation. Only labours of spontaneous onset in the pregnancies
      of women at term were studied. The incidence of pregnancy outcomes were assessed
      by presenting estimates of relative risk (RR) and their 95% confidence intervals
      (CI). RESULTS: Only 51.1% of women who received augmentation achieved a normal
      vaginal delivery compared with 76.5% of women who did not need augmentation (RR
      0.67; CI 0.63-0.71). Contributory factors to this disparity included a greater
      number of Caesarean sections (14.4% versus 6.6%; RR 2.18 CI 1.74-2.67), forcep
      deliveries (12.8% versus 5.3%; RR 2.41 CI 1.93-3.01) and ventouse deliveries
      (21.7% versus 11.5%; RR 1.89 CI 1.62-2.21) being performed among augmented
      labours as compared to normal progressive labours. CONCLUSION: Significant
      improvements in the management of labours which fail to progress are needed if
      normal vaginal delivery rates are to approach those seen in labours which
      progress without the need for augmentation.

PMID- 15955618
TI  - Models of ovarian cancer--are we there yet?
AB  - Ovarian cancer is the most lethal of all gynecological cancers and arises most
      commonly from the surface epithelium. Successful clinical management of patients
      with epithelial ovarian cancer is limited by the lack of a reliable and specific
      method for early detection, and the frequent recurrence of chemoresistant
      disease. Experimental models are of crucial importance not only to understand the
      biological and genetic factors that influence the phenotypic characteristics of
      the disease but also to utilize as a basis for developing rational intervention
      strategies. Ovarian cancer cell lines derived from ascites or primary ovarian
      tumors have been used extensively and can be very effective for studying the
      processes controlling growth regulation and chemosensitivity or evaluating novel
      therapeutics, both in vitro and in xenograft models. While our limited knowledge
      of the initiating events of ovarian cancer has restricted the development of
      models in which the early pathogenic events can be studied, recent advances in
      the ability to manipulate gene expression in ovarian surface epithelial cells in
      vitro and in vivo have begun to provide insights into the molecular changes that
      may contribute to the development of ovarian cancer. This review highlights the
      strengths and weaknesses of some of the current models of ovarian cancer, with
      special consideration of the recent progress in modeling ovarian cancer using
      genetically engineered mice.

PMID- 15955619
TI  - Genistein potentiates the growth inhibitory effects of 1,25-dihydroxyvitamin D3
      in DU145 human prostate cancer cells: role of the direct inhibition of CYP24
      enzyme activity.
AB  - In a search for improved therapies for prostate cancer, we investigated the
      effect of genistein in combination with 1alpha-25-dihydroxyvitamin D3
      [1,25(OH)2D3], on the growth of DU145 human prostate cancer cells. DU145 cells
      were very resistant to the growth inhibitory action of 1,25(OH)2D3 or genistein
      when administered individually. However, the combination caused a significant
      growth inhibition seen at lower concentrations of both agents. 1,25(OH)2D3
      induces the expression of the CYP24 gene, which codes for the enzyme that
      initiates the catabolism of 1,25(OH)2D3. We showed for the first time that
      genistein at low doses (50-100 nM) directly inhibited CYP24 at the enzyme level.
      Addition of genistein to mitochondrial preparations inhibited CYP24 enzyme
      activity in a noncompetitive manner. CYP24 inhibition by genistein increased the
      half-life of 1,25(OH)2D3 thereby augmenting the homologous up-regulation of the
      vitamin D receptor (VDR) both at the mRNA and protein levels. Genistein co
      treatment enhanced 1,25(OH)2D3-mediated transactivation of the vitamin D
      responsive reporters OC-Luc and OP-Luc transfected into DU145 cells. Consistent
      with the growth inhibition due to the combination treatment, significant changes
      in the expression of genes involved in growth arrest and apoptosis were seen. We
      conclude that genistein potentiates the antiproliferative actions of 1,25(OH)2D3
      in DU145 cells by two mechanisms: (i) an increase in the half-life of 1,25(OH)2D3
      due to the direct inhibition of CYP24 enzyme activity and (ii) an amplification
      of the homologous up-regulation of VDR. Together these two effects lead to a
      substantial enhancement of the cellular responses to the growth inhibitory and
      pro-apoptotic signaling by 1,25(OH)2D3.

PMID- 15955620
TI  - Directional secretion and transport of leptin and expression of leptin receptor
      isoforms in human placental BeWo cells.
AB  - Placental leptin secretion has important implications for maternal adaptation to
      pregnancy, fetal growth and development, and local autocrine/paracrine actions
      within trophoblast. In this study we used a cell culture insert model to examine
      directional secretion of leptin from the basal and apical surfaces of human
      choriocarcinoma BeWo cells, and to assess the effects of dexamethasone and
      syncytialization. Additionally, the effects of dexamethasone on transcellular
      passage of leptin across BeWo monolayers, and on expression of the leptin
      receptor isoforms Ob-Rs and Ob-RL were examined. Leptin was secreted into both
      the basal and apical chambers and was stimulated by dexamethasone. Treatment of
      BeWo cells with forskolin induced syncytialization and loss of monolayer
      integrity, but resulted in a marked increase in total leptin secretion, an effect
      further enhanced by co-treatment with dexamethasone. Bidirectional transfer of
      125I-leptin between the apical and basal chambers of BeWo cell cultures was low
      but indicative of specific transcellular passage of leptin; transfer was
      unaffected by dexamethasone. Treatment of BeWo cells with forskolin increased Ob
      Rs mRNA expression, whilst Ob-RL mRNA expression increased in response to
      forskolin only in the presence of dexamethasone. In conclusion, our data show
      that leptin is secreted from both the apical and basal surfaces of BeWo placental
      cells and is increased by both syncytialization and glucocorticoids. Moreover,
      transport of exogenous leptin occurred in both the apical to basal and reverse
      directions, suggesting the potential for maternal-fetal exchange of leptin across
      the human placenta.

PMID- 15955621
TI  - Thioredoxin reductase as a novel molecular target for cancer therapy.
AB  - Tumor cell proliferation, de-differentiation, and progression depend on a complex
      combination of altered cell cycle regulation, excessive growth factor pathway
      activation, and decreased apoptosis. The understanding of these complex
      mechanisms should lead to the identification of potential targets for therapeutic
      intervention. Redox-sensitive signaling factors also regulate multiple cellular
      processes including proliferation, cell cycle, and pro-survival signaling
      cascades, suggesting their potential as molecular targets for anticancer agents.
      These observations suggest that redox-sensitive signaling factors may be
      potential novel molecular markers. We hypothesized that thioredoxin reductase-1
      (TR), a component of several redox-regulated pathways, may represent a potential
      molecular target candidate in response to agents that induce oxidative stress.
      There have been numerous biological studies over the last decade investigating
      the cell biological, biochemical, and genetic properties of TR both in culture
      and in in vivo models. In addition, using a series of permanent cell lines that
      express either a wild-type TR or a dominant mutant TR gene or a chemical agent
      that inhibits TR we demonstrated that TR meets most criteria that would identify
      a molecular target. Based on these results we believe TR is a potential molecular
      target and discuss potential clinical possibilities.

PMID- 15955622
TI  - Parp-1 deficiency does not enhance liver carcinogenesis induced by 2-amino-3
      methylimidazo[4,5-f]quinoline in mice.
AB  - The susceptibility of poly(ADP-ribose) polymerase-1 (Parp-1) knockout mice to 2
      amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced liver carcinogenesis was
      analyzed. Twelve-week-old male Parp-1(+/+), Parp-1(+/-) and Parp-1(-/-) mice of
      the C57BL/6 congenic strain were fed a diet containing IQ at a concentration of
      300 ppm or a control diet for 60 weeks. Hepatocellular carcinomas were observed
      only in 1/19, 2/18 and 1/17 of the Parp-1(-/-), Parp-1(+/-) and Parp-1(+/+) mice,
      respectively. Parp-1 deficiency did not affect the susceptibility of mice to
      carcinogenicity of IQ, which produces bulky DNA adducts that are repaired mainly
      through the nucleotide excision repair pathway. This result is in sharp contrast
      to the increased susceptibility of Parp-1(-/-) mice to carcinogenesis induced by
      alkylating agents that produce DNA damage repaired mainly through base excision
      repair and DNA strand break repair pathways.

PMID- 15955623
TI  - Recycling Fe(III)/Cr(III) hydroxide, an industrial solid waste for the removal of
      phosphate from water.
AB  - Industrial solid waste, Fe(III)/Cr(III) hydroxide, was investigated to assess the
      capacity for the removal of phosphate from aqueous solution. Langmuir and
      Freundlich isotherms were used to model the adsorption equilibrium data. The
      system follows both isotherms. Adsorption capacity was found to be 6.5 mg/g.
      Kinetic studies show that the adsorption obeyed second order kinetics.
      Thermodynamic parameters were evaluated. Overall adsorption process was
      endothermic and spontaneous. Optimum pH for phosphate adsorption was found to be
      4.0. Effect of coexisting anions has also been examined.

PMID- 15955624
TI  - Batch and column studies on biosorption of acid dyes on fresh water macro alga
      Azolla filiculoides.
AB  - The biosorption of Acid red 88 (AR88), Acid green 3 (AG3) and Acid orange 7 (AO7)
      by deactivated fresh water macro alga Azolla filiculoides was investigated in
      batch mode. Langmuir and Freundlich adsorption models were used for the
      mathematical description of the batch biosorption equilibrium data and model
      constants were evaluated. The adsorption capacity was pH dependent with a maximum
      value of 109.0 mg/g at pH 7 for AR88, 133.5 mg/g at pH 3 for AG3 and 109.6 mg/g
      at pH 3 for AO7, respectively, was obtained. The pseudo first and second order
      kinetic models were also applied to the experimental kinetic data and high
      correlation coefficients favor pseudo second order model for the present systems.
      The ability of A. filiculoides to biosorb AG3 in packed column was also
      investigated. The column experiments were conducted to study the effect of
      important design parameters such as initial dye concentration (50-100 mg/L), bed
      height (15-25 cm) and flow rate (5-15 mL/min) to the well-adsorbed dye. At
      optimum bed height (25 cm), flow rate (5 mL/min) and initial dye concentration
      (100 mg/L), A. filiculoides exhibited 28.1mg/g for AG3. The Bed Depth Service
      Time model and the Thomas model were used to analyze the experimental data and
      the model parameters were evaluated.

PMID- 15955625
TI  - Activated carbons from sewage sludge and discarded tyres: production and
      optimization.
AB  - This is a study about making use of two residual materials such as sludges from a
      sewage treatment plant and discarded tyres to generate activated carbons and
      later optimize the production process. H2SO4 and ZnCl2 were used as chemical
      activating agents. Liquid-phase adsorption tests were made using the produced
      carbons to retain methylene blue and iodine. The best precursor was sludge
      activated with ZnCl2. After optimization studies, the best production methodology
      involved a 1:1 ratio of sludge and ZnCl2, a heating rate of 5 degrees C/min up to
      650 degrees C and a residence time of 5 min. The resulting materials adsorbed up
      to 139.4 mg/g of methylene blue and 1358.5 mg/g of iodine. Nevertheless these
      carbons may leach Zn while using. To avoid this two treatments were carried out:
      one consisting of a coating with a polymer and another involving an intensive
      washing, which was seen to be more efficient.

PMID- 15955626
TI  - Vestibular afferent innervation in the vestibular efferent nucleus of rats.
AB  - To delineate the vestibular afferent innervation in the vestibular efferent
      nucleus in the brainstem, neurobiotin or biotinylated dextran amine was injected
      into the superior Scarpa's ganglion of Sprague-Dawley rats. The locations of
      vestibular efferent neurons in the brainstem were identified by neutral red or
      choline acetyltransferase staining. Of the three pairs of vestibular efferent
      nuclei, labeled fibers and bouton-like endings were found only within the
      dorsolateral vestibular efferent nucleus on the ipsilateral side. Labeled
      afferent terminals with bouton-like varicosities were observed in the vicinity of
      cell bodies or dendrites of these efferent neurons. Our findings suggest that
      vestibular primary afferents may exert direct influence on vestibular efferent
      neurons, constituting an ipsilateral close-loop arrangement in the central
      vestibular system.

PMID- 15955627
TI  - Periadolescent nicotine administration produces enduring changes in dendritic
      morphology of medium spiny neurons from nucleus accumbens.
AB  - The objective of the current study was to examine how periadolescent nicotine
      exposure affects dendritic morphology of medium spiny neurons from the nucleus
      accumbens shell. Male Long-Evans hooded rats were chronically administered
      nicotine or saline for a period extending from postnatal day 22 (p22) to p69.
      Nicotine and saline administration was via subcutaneously implanted osmotic
      pumps. At p144, 75 days after conclusion of nicotine administration, brains were
      processed for Golgi-Cox staining. Medium spiny neurons from the nucleus accumbens
      shell were digitally reconstructed. It was found that neurons from nicotine
      treated animals possessed significantly longer dendrites and a greater number of
      dendritic segments than control animals. A branch order analysis indicated that
      differences in dendritic length and segment number were most pronounced in third
      and fourth order segments. A subsequent behavioral experiment suggests that the
      observed anatomical changes are associated with enduring psychomotor differences.
      These findings indicate that periadolescent exposure to nicotine can result in
      long-lasting structural changes in the nucleus accumbens shell and are consistent
      with behavioral data suggesting that adolescent nicotine exposure may result in
      vulnerability to nicotine addiction in adulthood.

PMID- 15955628
TI  - Gastrin-releasing peptide induces c-Fos in the hamster suprachiasmatic nucleus.
AB  - The suprachiasmatic nuclei (SCN) contain the dominant circadian pacemaker in the
      mammalian brain. Retinal illumination at specific circadian phases resets the
      circadian pacemaker and induces the expression of several transcription factors,
      including c-Fos, in SCN neurons. Gastrin-releasing peptide (GRP) is made by SCN
      neurons and exogenous GRP mimics the resetting actions of photic stimuli on
      behavioural and cellular rhythms. We assessed the effects of microinjection of
      GRP into the SCN region at three phases of the circadian cycle on c-Fos
      immunoreactivity (-ir) in this structure. Microinjections of GRP increased levels
      of c-Fos-ir in the SCN. A distinct pattern of c-Fos-ir was seen following GRP
      administration in the early subjective night, with immunostaining localized to a
      dorsolateral region of the SCN. Pre-treatment with a GRP receptor antagonist
      failed to block GRP-evoked increases in c-Fos-ir and the antagonist alone was
      found to increase c-Fos-ir in the dorsolateral SCN. These results indicate that a
      subpopulation of SCN neurons is particularly sensitive to microinjection of GRP;
      activation of these neurons may be important for GRP's phase-delaying actions.
      Future studies using GRP receptor antagonists that lack intrinsic agonist
      activity will be needed to fully evaluate the role of these cells in photic
      entrainment.

PMID- 15955629
TI  - The G2019S LRRK2 mutation is uncommon in an Asian cohort of Parkinson's disease
      patients.
AB  - A common heterozygous leucine-rich repeat kinase 2 (LRRK2) mutation 6055G > A
      transition (G2019S) accounts for about 3-7% of familial Parkinson's disease (PD)
      and 1-1.6% sporadic PD in a number of European populations. To determine the
      prevalence of the G1019S mutation in our Asian population, we conducted genetic
      analysis of this mutation in 1000 PD and healthy controls. The G2019S mutation
      was not detected in any of our study subjects. The prevalence of G2019S mutation
      is rare (< 0.1%) in our population, suggesting that occurrence of this mutation
      may vary amongst different ethnic races. This has important clinical implication
      when implementing guidelines for genetic testing.

PMID- 15955631
TI  - Incidence of Cryptosporidium parvum in the dairy cattle population in a New York
      City Watershed.
AB  - A longitudinal study of 2-year duration was conducted to determine the risk, as
      measured by incidence rate, of Cryptosporidium parvum infection among dairy
      cattle in the Catskill/Delaware Watershed of New York City (NYC), and the factors
      that predispose animals to the likelihood of infection. A proportional sampling
      scheme with follow up at quarterly farm visits was employed for heifers and cows.
      Additionally, all calves born on the 39 study farms were sampled once during the
      first four weeks of life and at least once more before weaning. Samples were
      analyzed for the presence of C. parvum using a quantitative centrifugation
      concentration flotation technique and a C. parvum-specific enzyme-linked
      immunosorbent assay (ELISA). Of the 9914 fecal samples collected, 747 were found
      to contain C. parvum. The average number of oocysts detected was 1.3x10(5)/g
      (range: 1.0/g--8.2x10(6)/g). The average age at time of first detection of the
      organism was 15.0 days with a standard deviation of 6.59 days. The age range of
      animals infected with C. parvum in the study population was 3--60 days
      (inclusive). The unadjusted (crude) incidence rate of C. parvum among the entire
      study population was 2.05 per 1000 animal-days. The unadjusted incidence rate
      among pre-weaned calves was 15.55 per 1000 animal-days. After controlling for age
      and prior protozoal risk level, no seasonal impact on the incidence of C. parvum
      was detected among animals less than 61 days by negative binomial regression. A
      seasonal impact was identified among the oocyst counts of infected animals after
      controlling for age and prior protozoal risk level.

PMID- 15955630
TI  - Genotype combinations for monoamine oxidase-B intron 13 polymorphism and dopamine
      D2 receptor TaqIB polymorphism are associated with ever-smoking status among men.
AB  - Tobacco smoke inhibits monoamine oxidase-B (MAO-B) activity in vitro and in vivo,
      suggesting that MAO-B inhibition is a possible contributing factor to tobacco
      smoke addiction. Thus, MAO-B is a possible candidate gene for predisposition to
      smoking. The TaqIB polymorphism for the Dopamine D2 Receptor gene (DRD2) has been
      previously associated with smoking status, although with some contradictory
      results. We investigated whether genetic variants of MAO-B intron 13 and DRD2
      TaqIB polymorphism could be associated with smoking status among control
      subjects. There was no association of the intron 13 polymorphism itself with
      smoking status in either men or women. Similarly, no association with smoking
      status was observed for the TaqIB polymorphism of DRD2 itself. However, among
      men, there was an interaction between MAO-B intron 13 polymorphism and the DRD2
      TaqIB polymorphisms, in which subjects carrying MAO-B allele A and genotype B12
      of DRD2 were 2.50 times (95% CI=1.05-5.95) more likely to be ever-smokers than
      the pool of men carrying all other genotype combinations. These results
      demonstrate that particular combinations of genotypes for MAO-B and DRD2 genes
      are associated with significantly higher risk for smoking behavior in men, but
      not in women.

PMID- 15955632
TI  - Molecular analysis of the nitrile catabolism operon of the thermophile Bacillus
      pallidus RAPc8.
AB  - The gene cluster containing the nitrile hydratase (NHase) and amidase genes of a
      moderate thermophile, B. pallidus RAPc8 has been cloned and sequenced. The (5.9
      kb) section of cloned DNA contained eight complete open reading frames, encoding
      (in order), amidase (belonging to the nitrilase related aliphatic amidase
      family), nitrile hydratase beta and alpha subunits (of the cobalt containing
      class), a 122-amino acid accessory protein, designated P14K, a homologue of the
      2Fe-2S class of ferredoxins and three putative proteins with distinct homology to
      the cobalt uptake proteins cbiM, cbiN and cbiQ of the S. typhimurium LT2
      cobalamin biosynthesis pathway. The amidase and nitrile hydratase genes were
      subcloned and inducibly expressed in Escherichia coli, to levels of approximately
      37 U/mg and 49 U/mg, respectively, without the co-expression of additional
      flanking genes. However, co-expression of P14K with the NHase structural genes
      significantly enhanced the specific activity of the recombinant NHase. This is
      the first description of an accessory protein involved in thermostable NHase
      expression. Modelling of the P14K protein structure has suggested that this
      protein functions as a subunit-specific chaperone, aiding in the folding of the
      NHase alpha subunit prior to alpha-beta subunit association and the formation of
      alpha(2)beta(2) NHase holoenzyme.

PMID- 15955633
TI  - "Flypaper technique" a modified expansion method for preparation of postage stamp
      autografts.
AB  - The gold standard for management of extensive burn has been early excision,
      temporary allografting and final autografting. However, "lack of donor skin" is a
      challenge condition when autografting in the treatment of extensive burns.
      Designing an efficient and easy to apply expansion method may improve burn care
      quality and shorten the hospital stay period. From December 1998 to May 2004, we
      have performed fly paper technique postage stamp skin autografting for eight
      major burn patients in the Kaohsiung Medical University Hospital. By using a
      quick cutting plate, chessboard tray and petrolatum gauze, the skin islands can
      be uniformly located and correctly oriented on gauze. Then, the gauze with skin
      islands was grafted on to the wound. The wound healing time depends on the size
      of skin islands and expansion ratio. This method allows true expansion ratio up
      to nine times. The average wound healing times are 27.2 days for six times
      expansion and 34 days for nine times expansion. However, the burn scar needs
      further compression therapy to improve the cosmetic result. In comparison with
      the mesh technique, the skin islands are independent of each other, any
      dislodgement of a skin island will not interfere with the surrounding skin
      squares. When compared with the modified Meek technique, this method also offers
      rapid wound reepithilization but with lower cost. This flypaper technique is
      worthy of consideration in dealing with the extensive burns.

PMID- 15955634
TI  - Results of a protocol of transfusion threshold and surgical technique on
      transfusion requirements in burn patients.
AB  - INTRODUCTION: Blood loss and high rates of transfusion in burn centers remains an
      area of ongoing concern. Blood use brings the risk of infection, adverse
      reaction, and immunosuppression. METHODS: A protocol to reduce blood loss and
      blood use was implemented. Analysis included 3-year periods before and after
      institution of the protocol. All patients were transfused for a hemoglobin below
      8.0 gm/dL. RESULTS: Operations per admission did not change during the two time
      periods (0.78 in each). Overall units transfused per operation decreased from
      1.56+/-0.06 to 1.25+/-0.14 units after instituting the protocol (p<0.05). Also,
      units transfused per admission decreased from 1.21+/-0.15 to 0.96+/-0.06 units of
      blood (p<0.05). This was noticed particularly in burns of less than 20% surface
      area, declining from 386 to 46 units after protocol institution, from 0.37 to
      0.04 units per admission, and from 0.79 to 0.08 units per operation in this group
      of smallest burns. There was no change noted in the larger burns. CONCLUSIONS:
      This study suggests that a defined protocol of hemostasis, technique, and
      transfusion trigger should be implemented in the process of burn excision and
      grafting. This will help especially those patients with the smallest burns,
      essentially eliminating transfusion need in that group.

PMID- 15955635
TI  - Costal cartilage necrosis--an unusual complication of electric injury.

PMID- 15955636
TI  - Cerium nitrate in the management of burns.
AB  - BACKGROUND: The introduction of early excision of the burn eschar has contributed
      to a reduction in burn-related mortality but is not appropriate in all
      circumstances. Cerium nitrate has been used since 1976, usually in combination
      with silver sulphadiazine, to improve outcome where early excision is not
      performed. However, has still not gained universal acceptance. The evidence for
      its use is reviewed. METHODS: A MEDLINE search was performed for the years 1966
      2003 using keywords 'cerium', 'sulphadiazine', 'Flammacerium', 'lanthanides' and
      'topical therapy for burns'. The reference lists of key articles were then sifted
      for other relevant articles. RESULTS: Cerium has been shown to reduce mortality
      and morbidity in the treatment of severe burns. This benefit is derived from its
      action on the burn eschar. It binds and denatures the lipid protein complex
      liberated from burnt skin that is responsible for the profound immunosuppression
      associated with major cutaneous burns. It has only limited antimicrobial
      properties. CONCLUSIONS: Cerium nitrate is an excellent topical treatment for
      most cutaneous burns not undergoing immediate excision and closure.

PMID- 15955637
TI  - Subjective indicators as a gauge for improving organizational well-being. An
      attempt to apply the cognitive activation theory to organizations.
AB  - Globally, organizations are undergoing substantial changes, commonly resulting in
      significant employee stress. However, facing similar stressors and challenges,
      departments within an organizations, as well as companies within the same area of
      business, vary in the way they cope with change. It was hypothesized that
      collective uncertainty about the future as well as unclear organizational goals
      contribute to chronic stress in organizations exposed to change. Applying the
      theoretical cognitive activation theory of stress--CATS--model by Ursin and
      Eriksen at an organizational level, support was found for the above hypothesis.
      Changes in chronic stress indicators between two assessments were related to
      clarity of organizational goals. It is suggested that the CATS model might be
      fruitful, not only in understanding variations in individual stress responses and
      experiences, but also to interpret and manage organizational stress. By doing so,
      both organizational health and well-being will improve, creating enterprises with
      healthy employees and healthy productivity and economic results.

PMID- 15955638
TI  - CNS depressant activity of Lecaniodiscus cupanioides.
AB  - The aqueous root extract of Lecaniodiscus cupanioides was used to study the
      central nervous system depressant activity pattern of the plant. The extract
      protected mice from strychnine-induced convulsion at 400 mg/kg p.o. and 100 mg/kg
      i.p. A dose-dependent prolongation of seizure latency was produced at 400 mg/kg,
      p.o. and 100 mg/kg i.p. for strychnine-induced seizure; and at 400 mg/kg p.o. and
      100 mg/kg i.p. for picrotoxin-induced seizure. Moreover, the CNS depressant
      activity of the extract (200 mg/kg p.o. and 50 mg/kg i.p.) was demonstrated by a
      significant prolongation of 40 mg/kg, pentobarbitone sleeping time, and
      significant reduction in exploratory behavior of mice at a dose of 400 mg/kg
      p.o., with both effects comparable to effects produced by 4 mg/kg chlorpromazine.
      Acute oral toxicity test, up to 14 days, did not produce any visible signs of
      toxicity; however, acute (24 h) i.p toxicity test produced a dose-dependent
      mortality with LD50 of 455.2 mg/kg.

PMID- 15955639
TI  - Differential modulation of ochratoxin A absorption across Caco-2 cells by dietary
      polyphenols, used at realistic intestinal concentrations.
AB  - The effect of polyphenols (PPs) on the absorption of ochratoxin A (OTA), a food
      borne mycotoxin, was investigated in an in vitro model of the human intestinal
      barrier based on Caco-2 cells cultivated in a bicameral system. Two intraluminal
      concentrations of OTA approaching physiological levels were chosen (0.75 nM and
      7.5 nM) through calculations based on estimated daily intakes. The transport of
      OTA from the apical to the basolateral side of Caco-2 cells, i.e. absorption, was
      directly proportional to its initial apical concentration. Very significant
      increase in both OTA absorption and cellular accumulation was observed upon co
      incubation with certain PPs, i.e. chrysin, quercetin, genistein, biochanin A,
      resveratrol, at concentrations that should be encountered in the gastrointestinal
      tract, as well as with MK571, a specific inhibitor of MRPs efflux pumps. As these
      PPs have been reported to be metabolized in Caco-2 cells into substrates of MRP
      2, we hypothesize that PPs and/or metabolites could impair the OTA efflux,
      previously proposed to be mediated by the MRP-2, through competitive inhibition
      for the pump. These data imply that interactions between OTA and PPs may lead to
      a greater bioavailability of the mycotoxin in the bloodstream with possible
      adverse effects for human health.

PMID- 15955640
TI  - GnRH analogues--agonists and antagonists.
AB  - GnRH analogues have achieved widespread clinical use for the control of
      reproduction in animals. Over 2000 analogues of GnRH have been developed and
      tested over the last 30 years. Paradoxical anti-fertility effects are seen when
      the more potent agonists are delivered continuously to animals. The evaluation of
      agonist potency depends largely on the model used and wide varying potencies are
      reported for the same agonist. The design of analogues has centered on improving
      the receptor-binding and subsequent activation for agonists. Antagonists have
      been produced with strong receptor binding but without activation. Deslorelin is
      classified as a superagonist, with a potency perhaps 100 times that of GnRH. The
      interactions between agonist potency, dose and duration of treatment largely
      determine whether pro- or anti-fertility effects are induced. Due to the peptide
      nature of the synthetic analogues oral administration and potential
      gastrointestinal enzymatic degradation poor bioavailability results necessitating
      a parenteral delivery system. Some GnRH antagonists have been associated with
      significant histamine release, inhibiting their widespread use. More recently,
      antagonists have been developed that avoid this side effect without compromising
      potency. However the GnRH antagonist development has lagged behind that of the
      agonists, in part related to their high cost of production. In conclusion, GnRH
      agonists have achieved widespread clinical use in animals for controlling
      reproduction in either pro- or anti-fertility roles, yet antagonist development
      has been slower.

PMID- 15955641
TI  - Estimated numbers of postmenopausal women treated by hormone therapy in France.
AB  - OBJECTIVES: To estimate the number of women aged 50-69 years treated by hormone
      therapy (HT) in France before Women's Health Initiative's (WHI) results and to
      evaluate the potential decrease of HT prescriptions since the publication of WHI
      clinical trial. METHODS: We used data from eight computerized databases of French
      cohort studies providing information on HT and constituted by women aged over 50
      years living in metropolitan France. From these, we used direct standardization
      on the French population to estimate the prevalence of HT users across 5 years
      age groups. Data from the National Health Insurance Agency on two time-periods
      November 2002-January 2003 and November 2003-January 2004 were used to evaluate
      the evolution of HT prescriptions since WHI's publication among women aged 50-69
      years living in the Rhone-Alpes region. RESULTS: The crude prevalence of HT users
      among women aged 50-69 years was 52.3% (51.8-52.8) and corresponds to a
      standardized prevalence of 35.7% (35.1-36.4), that is about 2.56 (2.51-2.59)
      million women. Standardized prevalence was the highest in 50-54 years age group
      then it decreased significantly across the older age groups (p<10(-6)). HT
      reimbursements decreased significantly between the two studied time-periods in
      the Rhone-Alpes region (p<10(-6)) from -14 to -45%, depending on the considered
      age groups (65-69 or 50-54 years). CONCLUSIONS: Although WHI results have been
      criticized by French professional societies based on the fact that treatments
      used were different in France--mainly transdermal estrogens--and that French
      postmenopausal women were at lower vascular risk than those of the WHI, the
      release of this study had effect on the prescription before the French regulatory
      agency (AFSSAPS) edited limiting recommendations for HT prescription. Further
      efforts have to be made to collect systematically information on preventive
      treatments used at menopause followed by evaluation studies.

PMID- 15955642
TI  - The association between early menopause and risk of ischaemic heart disease:
      influence of Hormone Therapy.
AB  - Randomised clinical trials find no protection against development of ischaemic
      heart disease by use of Hormone Therapy (HT) after the age of 50 years.
      Observational studies suggest that early menopause is a risk factor for ischaemic
      heart disease. Yet, a clinical very relevant question is whether HT reduces this
      risk associated with early menopause. OBJECTIVE: To analyse whether early
      menopause based on various causes are independent risk factors for ischaemic
      heart disease, and to investigate whether the risks are modified by use of HT.
      METHODS: In a prospective cohort study questionnaires were mailed to Danish
      female nurses above 44 years of age in 1993. Information on menopause, use of HT
      and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the
      questionnaire, among them 10.533 were postmenopausal with definable menopausal
      age, free of previous ischaemic heart disease, stroke or cancer. Through
      individual linkage to national register incident cases of ischaemic heart disease
      were identified until end of 1998. RESULTS: Menopause below both age 40 and 45
      was associated with an increased risk of ischaemic heart disease, seeming most
      pronounced for women who had an early ovariectomy but also among spontaneous
      menopausal women. Generally HT did not reduce the risk except for the early
      ovariectomised women, where no increased risk of ischaemic heart disease for HT
      users was found. CONCLUSION: We found an increased risk of ischaemic heart
      disease associated with early removal of the ovaries that might be reduced with
      HT. The present study need confirmation from other studies but suggests that
      early ovariectomised women could benefit from HT.

PMID- 15955643
TI  - Structural characteristics and crystal polymorphism of three local anaesthetic
      bases crystal polymorphism of local anaesthetic drugs: part VII.
AB  - Benzocaine (BZC), butambene (BTN) and isobutambene (BTI) are basic local
      anaesthetic agents of the ester type, preferentially used for surgery and dental
      procedures. The compounds, official in the USP (BZC and BTN) and Ph. Eur. (BZC),
      were each found to exist in two polymorphic crystal forms and their solid state
      characteristics have been determined by thermomicroscopy, differential scanning
      calorimetry (DSC), FTIR-, FT-Raman-spectroscopy as well as X-ray powder
      diffractometry. This work further emphasizes the comparison of solid state
      characteristics of three compounds with closely related structural features on
      molecular level, leading to opportunities for the investigation of structure
      property relationships. Mod. I0 is the particular thermodynamically stable form
      at room temperature in all of the three systems. This form is present in
      commercial products and can be crystallized from solvents at room conditions.
      Mod. II can be obtained by annealing the supercooled melt or fast cooling of a
      saturated solution, respectively. The endothermic transformation of mod. II to
      mod. I0 upon heating confirms that mod. I0 is thermodynamically stable at ambient
      conditions (heat of transition rule) whereas mod. II is enantiotropically related
      to mod. I0, i.e. is metastable at temperatures above the transition temperature.
      The metastable forms show different kinetic stabilities at room temperature.

PMID- 15955644
TI  - The examination of polysaccharides as potential antioxidative compounds for
      topical administration using a lipid model system.
AB  - Aim of this study was the detection of polysaccharides with antioxidative
      properties as potential lipid protectors for topical administration. The effects
      of eight different polysaccharides on UV irradiation induced lipid peroxidation
      were investigated in a concentration dependent manner. An aqueous linolenic acid
      dispersion was used as an in vitro test system to examine the influences of
      acacia gum, agar agar, alginic acid, guar gum, novelose 330 and xanthan gum on
      the lipid peroxidation level after UV exposure. Four different samples of pectin
      and locust bean gum resulting from a swing mill grinding series were tested as
      well. Iron ions were added as transition metal catalysts. A UV irradiation device
      was used to create high level radiation. The amount of lipid peroxidation
      secondary products was quantified by the thiobarbituric acid assay detecting
      malondialdehyde. All of the tested polysaccharides showed antioxidative effects
      at least at one concentration. For acacia and xanthan gum, a concentration
      dependency of the protective effects was measured. The samples of agar agar, guar
      gum and novelose 330 acted antioxidatively without showing any concentration
      dependency. For alginic acid, prooxidative effects were determined. A correlation
      between grinding time and the effects of pectin and locust bean gum on the model
      lipid was not observed. The administration of lipid protective polysaccharides in
      cosmetic formulations or sunscreens could be helpful for the protection of the
      human skin against UV induced damage. In vivo experiments with the lipid
      protective polysaccharides found in this study should follow.

PMID- 15955645
TI  - Significance of lipid matrix aging on in vitro release and in vivo
      bioavailability.
AB  - A polyglycolised glyceride carrier, Gelucire 50/13, was incorporated with
      paracetamol as a model drug, filled into hard gelatin capsules and stored at
      three different temperatures for various lengths of time. The resultant
      solidified matrix within the capsule was subjected to thermal analysis using
      differential scanning calorimetry (DSC) to ascertain its supramolecular
      structure. Polymorphic transformations towards more stable gelucire forms were
      observed upon aging the matrices, with samples stored at a temperature near the
      melting range of the lower temperature gelucire melting fraction showing the most
      profound changes. The increase in the rate of drug release from aged samples
      could be correlated to the alterations to the supramolecular structure of the
      gelucire. Accelerated drug release from aged samples could also be seen from in
      vivo studies using healthy human volunteers, although the extent of absorption
      was not affected. Therefore, even though the sustainability of release may be
      compromised by aging the gelucire matrices, the bioavailability of the
      incorporated drug is unlikely to be affected.

PMID- 15955646
TI  - Hepatoprotective activity of Gundelia tourenfortii.
AB  - Gundelia tourenfortii (L.), is used as an occasional food, and its extracts have
      been used for prevention and treatment of liver diseases in Iran. The effects of
      different concentrations of the hydroalcoholic extract of dried powdered
      footstalks of Gundelia tourenfortii were investigated on CCl4-induced
      hepatotoxicity using in vivo model in rats and isolated rat hepatocytes. Rats
      received different concentrations of the Gundelia tourenfortii extract by i.p.
      injection for three consecutive days before the injection of CCl4 (i.p.). After
      24 h, they were bled and their livers were dissected for biochemical and
      histopathological studies. The results showed that the Gundelia tourenfortii
      extract could protect the liver against CCl4-induced damages with doses of 200
      and 300 mg/kg, but concentrations higher than 300 mg/kg were less effective. For
      in vitro studies, the extract was added to the suspension of freshly isolated rat
      hepatocytes incubated in Krebs-Henseleit buffer under a flow of 95% O2 and 5%
      CO2, 20 min before the addition of 10mM of CCl4. The Gundelia tourenfortii
      extract with concentrations of 0.2-0.8 mg/ml protected the cells against CCl4
      induced cytotoxicity, and its maximum protective effect was about 0.5 mg/ml, but
      concentrations of 1.0 mg/ml and higher increased the CCl4-induced cytotoxicity.
      The Gundelia tourenfortii extract itself was toxic towards isolated hepatocytes
      with concentrations above 1.0 mg/ml. Therefore, the results of the present study
      support the traditional believes on hepatoprotective effects of Gundelia
      tourenfortii, however, high concentrations were hepatotoxic.

PMID- 15955647
TI  - Hypolipidaemic and antioxidant effect of Enicostemma littorale Blume aqueous
      extract in cholesterol fed rats.
AB  - Enicostemma littorale aqueous extract (1.5 g/100 g body weight/day, p.o.) was
      administered to rats along with hypercholesterolaemic diet for 6 weeks and the
      hypolipidaemic and antioxidant effect was evaluated. Feeding cholesterol
      increased serum cholesterol, serum triglycerides, LDL, VLDL and decreased HDL
      levels as compared to normal diet fed rats. Enicostemma littorale treatment
      increased HDL levels and decreased serum cholesterol, triglyceride, LDL, VLDL,
      LDL/HDL ratio. In addition, treatment with the extract showed a decrease in
      activities of erythrocyte catalase, superoxide dismutase and lipid peroxidation
      levels, with an increase in reduced glutathione levels as compared to cholesterol
      fed untreated rats. Liver and kidney cholesterol levels and triglyceride levels
      were also decreased in Enicostemma littorale treated rats. Hepatic HMG CoA
      reductase activity was significantly reduced in the extract treated
      hypercholesterolemic rats. Lovastatin was used as a reference drug. The
      hypolipidaemic and antioxidant effect of Enicostemma littorale aqueous extract in
      cholesterol fed rats is being reported for the first time.

PMID- 15955648
TI  - Antihypertensive effect of Lepidium sativum L. in spontaneously hypertensive
      rats.
AB  - The antihypertensive and diuretic effects of the aqueous extract of Lepidium
      sativum L. (LS) were studied both in normotensive (WKY) and spontaneously
      hypertensive rats (SHR). Daily oral administration of the aqueous LS extract
      (20mg/kg for 3 weeks) exhibited a significant decrease in blood pressure (p<0.01)
      in SHR rats while in WKY rats, no significant change was noted during the period
      of treatment. The systolic blood pressure was decreased significantly from the
      7th day (p<0.05) to the end of treatment (p<0.01) in SHR rats. The aqueous LS
      extract enhanced significantly the water excretion in WKY rats (p<0.001) but no
      statistically significant change was observed in SHR rats. Furthermore, oral
      administration of aqueous LS extract at a dose of 20mg/kg produced a significant
      increase of urinary excretion of sodium (p<0.05), potassium (p<0.01) and
      chlorides (p<0.01) in WKY rats. In spontaneously hypertensive rats, the aqueous
      LS extract administration induced a significant increase of urinary elimination
      of sodium (p<0.01), potassium (p<0.001) and chlorides (p<0.001). Glomerular
      filtration rate showed a significant increase after oral administration of LS in
      normal rats (p<0.001) while in SHR rats, no significant change was noted during
      the period of treatment. Furthermore, no significant changes were noted on heart
      rate after LS treatment in SHR as well as in WKY rats. Our results suggest that
      daily oral administration of aqueous LS extract for 3 weeks exhibited
      antihypertensive and diuretic activities.

PMID- 15955649
TI  - Recognition by forensic facial approximation: case specific examples and
      empirical tests.
AB  - The skeletal remains of one individual found near Adelaide in 1994, although not
      known at the time, were the first evidence of what was to be a serial killing
      reported to have resulted in the highest casualty list to date in Australia (12
      victims). Since the usual methods of identification could not be used or were
      unsuccessful on these remains, facial approximations were produced and advertised
      over the 4-year period following their discovery, in an attempt to help to
      identify them. However, no identification was made. In 1999, the remains were
      reported to be identified by radiographic comparison. Approximately 3 months
      before this identification was made, another facial approximation was produced by
      the first author (CNS), but this face was never advertised in the media. Although
      rarely reported in the literature, this paper provides an example where facial
      approximation methods were not successful in a forensic scenario. The paper also
      reports on empirical tests of the facial approximation created by the first
      author to determine if this facial approximation might have been useful had it
      been advertised. The results provide further evidence that high resemblance of a
      facial approximation to the target individual does not indicate recognizability,
      as the facial approximation was poorly recognized even though it bore good
      resemblance to the target individual. The usefulness of facial approximation
      techniques is discussed within the context of this case and more broadly. Methods
      used to assess the accuracy of facial approximations are also discussed and
      further evaluated.

PMID- 15955650
TI  - Extraction and analysis of flunitrazepam/7-aminoflunitrazepam in blood and urine
      by LC-PDA and GC-MS using butyl SPE columns.
AB  - The forensic toxicology community has recognized flunitrazepam and its metabolite
      (7-aminoflunitrazepam) as compounds of concern for several years. In this
      procedure, the analytes were extracted from whole blood and urine onto single
      mode solid phase cartridges (butyl) using nitrazepam as an internal standard. The
      columns were washed with distilled water and hexane. All three compounds were
      eluted from the sorbent using an ethyl acetate-methanol solvent mixture. After
      collection and evaporation of the solvent, the residue was dissolved in A, 0.1%
      (v/v) aqueous trifluoroacetic acid for HPLC-PDA analysis or B, ethyl acetate for
      derivatization with pentafluoropropionic anhydride (PFPA) for analysis by gas
      chromatography-mass spectrometry (selected ion monitoring, SIM). A limit of
      quantitation for this method using HPLC-PDA was found to be 5 and 1.0 ng mL(-1)
      by SIM.

PMID- 15955651
TI  - 12 Y-chromosomal STR haplotypes in Japanese.
AB  - Haplotypes and allele frequencies of 12 Y-STRs were examined in a population
      sample of 381 Japanese male volunteers. A total of 315 haplotypes were
      identified, of which 288 haplotypes were unique, and 18, three, three, two, one
      and one were found in two, three, four, five, eight and 18 individuals,
      respectively. Total gene diversity was 0.997.

PMID- 15955652
TI  - Criminalystic: effectiveness of lysochromes on the developing of invisible
      lipstick-contaminated lipmarks on human skin. A preliminary study.
AB  - Latent prints are an important evidence for identification. Nowadays, the
      technical means, the implementation of image processing techniques and the use of
      database makes it possible to detect and get information from some prints that
      seem to be useless at first sight. On the other hand, the possibility of using
      the print as a DNA source has to be considered, so as to double its identifying
      value. Human skin is a particularly difficult surface for developing this kind of
      evidences. Although different methods for locating and developing latent
      fingerprints on the skin have been already described, it has not been found any
      method, at the revised bibliography, to obtain and develop invisible lipmarks,
      that is, lipmarks from protective lipstick, or permanent or long-lasting
      lipstick. The aim of the work that follows is to determine the effectiveness of
      several reagents for developing invisible lipmarks on the corpses' skin.
      Preliminary results show that, under the described experimental conditions, the
      reagents used, Sudan III, Oil Red O and Sudan Black, are effective for obtaining
      recent latent lip prints on corpse's skin.

PMID- 15955653
TI  - A study of the effectiveness of chemosurgery with trichloroacetic acid for
      Japanese cedar pollenosis in terms of the chemical mediator levels in the nasal
      discharge and results of nasal provocation testing.
AB  - OBJECTIVE: The purpose of the present study was to investigate the effectiveness
      of chemosurgery with 80w/v% trichloroacetic acid (TCA) for the treatment of
      Japanese cedar pollenosis. The effectiveness of this treatment was evaluated in
      terms of the levels in the nasal washings of the chemical mediators histamine and
      eosinophil cationic protein, and the reactivity in the nasal provocation test.
      METHODS: Patients of cedar pollenosis were divided into two groups, the TCA
      treated group (n=90) and the group that was not treated with TCA (nonTCA-treated
      group) (n=79), according to whether or not they received TCA treatment. In both
      the groups, the levels of the two aforementioned mediators in the nasal washings
      were measured during the pollen dispersal season. In addition, allergen
      provocation tests were performed using the disk method in volunteers from both
      the groups during the non-pollen dispersal season. The results of the above two
      determinations were compared statistically between the two groups. RESULTS: The
      results revealed significantly lower levels of the two mediators in the TCA
      treated group than in the nonTCA-treated group (p<0.01). There was also a greater
      tendency for the subjects in the TCA-treated group as compared to those in the
      nonTCA-treated group to show negative reactivity in the allergen provocation test
      (p<0.01). CONCLUSION: Regional suppression of the allergic reaction to Japanese
      cedar pollen appears to occur as a result of chemosurgery with TCA performed as a
      day surgery.

PMID- 15955654
TI  - The galenic venous system: surgical anatomy and its angiographic and magnetic
      resonance venographic correlations.
AB  - OBJECTIVE: This study aims at evaluating the adequacy of digital subtraction
      angiography and magnetic resonance venography in imaging of the galenic venous
      system for surgical planning of approaches to the pineal region. Anatomical
      dissections were carried out in 10 cadavers of several age groups and these were
      compared to imaging findings in 10 living subjects. METHODS: The presence or
      absence of 10 predetermined veins or vein groupings belonging to the galenic
      venous system were prospectively analyzed in 10 cadaver dissections and imaging
      findings of 10 age matched human subjects. The studied vessels were the vein of
      galen, the internal cerebral veins, both basal vein of Rosenthals, internal
      occipital vein, occipitotemporal veins, precentral cerebellar veins, tectal
      veins, pineal veins, superior vermian veins (including superior cerebellar veins
      (SCVs)) and posterior pericallosal veins. Each of the subjects had both digital
      subtraction angiography and magnetic resonance venography studies performed.
      Diagnostic digital subtraction angiography was performed using the transfemoral
      route and the venous phase was used for the study. Magnetic resonance venography
      was performed in 1.5 T MRI equipment using the 2D-TOF sequence. All studies were
      reported to be normal. RESULTS: There was wide variation in the anatomy of the
      galenic venous system. There were interpersonal, intrapersonal and age related
      variations. Both the digital subtraction angiography and the magnetic resonance
      venography were efficient at demonstrating large veins. However, smaller veins
      were less readily demonstrated in either study. The general sensitivities of the
      digital subtraction angiography and the magnetic resonance venography for the
      galenic venous system were 45.5% and 32.5%, respectively. Surgically important
      veins were missed in most studies. CONCLUSIONS: Anatomically, the galenic venous
      system is highly variable. This variability is caused by interpersonal,
      intrapersonal and age related differences and causes each individual galenic
      venous system to be unique. Therefore, modern neurosurgical procedures require
      anatomical information on individual differences. Current radiological methods of
      digital subtraction angiography and magnetic resonance venography fail short of
      providing the necessary information. New and more sophisticated MRI technology
      may fulfill this need.

PMID- 15955655
TI  - Utilization of luminescent technology to develop a kinase assay: Cdk4 as a model
      system.
AB  - Protocols to assess kinase activity generally include radioactive methods,
      fluorescent polarization technology and the use of specific antibodies. Here, a
      simple, effective, non radioactive method to measure kinase activity of
      immunoprecipitated proteins is described. Cdk4, a cell cycle dependent enzyme,
      was immunoprecipitated from whole cell extracts and used in kinase reactions.
      This system has been developed taking advantage of the kinase-Glo reagent
      (Promega), based on ATP depletion technology, but with a wider range of
      applications. The original aim of the commercial kit is the evaluation of kinase
      activity of highly purified enzymes, while this system enabled the evaluation of
      native kinases, retrieved by immunoprecipitation. This method was highly
      homogeneous and did not require any kind of separation or purification as well.
      Moreover, it was suitable for basic research and may be useful for low-medium
      throughput pharmaceutical screening of chemical libraries.

PMID- 15955656
TI  - A validated HPLC stability-indicating method for the determination of diacerhein
      in bulk drug substance.
AB  - A novel stability-indicating high-performance liquid chromatographic (HPLC)
      method was developed and validated for the assay of diacerhein in bulk forms.
      Diacerhein was found to degrade in alkaline and acidic conditions and also under
      oxidative stress. The drug was stable to dry heat and in presence of light.
      Resolution of drug, its potential impurities and degradation products were
      achieved on a RP18 (endcapped) column utilizing 0.1 M phosphoric acid and
      methanol (40:60, v/v) as eluent at the detection wavelength of 254 nm. The
      validation studies were carried out fulfilling International Conference on
      Harmonisation (ICH) requirements. The procedure was found to be specific, linear,
      precise (including intermediate precision), accurate and robust.

PMID- 15955657
TI  - Fear-relevant change detection in spider-fearful and non-fearful participants.
AB  - Features of threatening stimuli are proposed to be processed fast and
      automatically, as they call for immediate attention. Phobic patients typically
      exhibit these attentional biases for stimuli that are relevant for their
      particular type of fear. In the present study, it was examined whether a change
      detection paradigm can be used to study attentional bias for fear-related
      stimuli. Twenty-five spider-fearful and 25 non-fearful participants were
      confronted with a series of pictures, in which sometimes a spider gradually
      appeared, sometimes a fear-irrelevant stimulus appeared, and sometimes no change
      occurred. Participants had to indicate whenever they noticed a change in the
      picture. Results showed a pattern of fear-relevant change detection. That is,
      spider changes were more frequently detected than fear-irrelevant changes, and
      spider-fearful participants detected more spider changes than non-fearful
      controls. Further, it was found that high-trait anxious participants did not
      detect more changes than low-trait anxious participants.

PMID- 15955658
TI  - Panic and epilepsy.
AB  - Research is presented to support a hypothesis that panic attacks, when they have
      the same clinical signs as the epileptic consciousness, should be diagnosed as
      partial seizures with a psychic content. After setting out the four clinical
      signs defining it (suddenness, automatic nature, great intensity and
      strangeness), an extensive review of the literature is made in search of
      scientific information to support the hypothesis, which reveals a wealth of
      concurring scientific evidence, at both the clinical and preclinical levels, to
      support the hypothesis presented here. In conclusion, new research is proposed
      with a view to drawing up interviews and clinical scales in order to quantify the
      four clinical signs objectively.

PMID- 15955659
TI  - Effects of long-term psychostimulant medication on growth of children with ADHD.
AB  - The objective was to assess the effects of long-term psychostimulant medication
      on growth parameters in children with attention deficit hyperactivity disorder
      (ADHD). Eighty-nine children diagnosed with ADHD treated by prescribed
      psychostimulant medications were followed with repeated growth measures over a 3
      years duration. Anthropometric measurements were recorded at baseline, 3, 6, 12,
      24, and 36 months. Medical records were reviewed for demographic information,
      medication side effects and appetite suppression. Body mass index (BMI) and z
      scores were determined at each follow up visit. Descriptive and analytical
      analyses by repeated measures analysis of varianc were performed. Significant
      weight loss was documented mostly during the first few months of treatment with
      stimulants. Although z-scores for weight showed significant changes over the 2
      years of treatment, further analysis of the changes did not reach clinical
      significance. BMI growth was within normal limits throughout the duration of
      treatment. Baseline weight predicted weight loss for heavier children only. Pre
      pubertal children were more subject to weight loss than children during puberty,
      as well as children for which appetite suppression was reported. No long-term
      impact on height was noted. Different stimulant medication did not differ in
      their effects on growth. Generally, parents and providers can be reassured that
      growth changes with long-term stimulant therapy are not clinically significant
      for a diverse group of children with ADHD.

PMID- 15955660
TI  - Neurobehavioral evaluation of rhesus monkey infants fed cow's milk formula, soy
      formula, or soy formula with added manganese.
AB  - The possible neurobehavioral effects of excess manganese in soy formula were
      studied. Male rhesus monkeys (n=8/group) were fed a commercial cow's milk based
      formula (Control), a commercial soy protein based formula (Soy), or the soy
      formula with added manganese (Soy+Mn) from birth to 4 months of age. Soy formulas
      naturally have higher manganese (Mn) content than cow's milk formulas. Monkeys
      received behavioral evaluations, growth measurements, and cerebrospinal fluid
      (CSF) sampling from birth to 18 months of age. Soy and Soy+Mn groups engaged in
      less play behavior and more affiliative clinging in social dyadic interactions.
      These groups also had shorter wake cycles and shorter periods of daytime
      inactivity than controls. An impulsivity test was sensitive to the Soy group
      diet. The Soy+Mn group also had a blunted response to the dopamine agonist
      apomorphine. Groups did not differ significantly in CSF dopamine and serotonin
      metabolite concentrations, but these concentrations were correlated with several
      tasks affected by experimental formula. This experiment suggests that components
      of soy formula, including Mn, may influence brain development as reflected in
      behavioral measures.

PMID- 15955661
TI  - Ultrasound guided lithotripsy of salivary calculi using an electromagnetic
      lithotriptor.
AB  - Sialolithiasis is a common disease of the major salivary glands. A supplement to
      the traditional therapies is extracorporeal shock wave lithotripsy of the
      calculus. This method has been adopted from the therapy of renal or bladder
      calculi. Patients with a solitary calculus of parotid or submandibular gland were
      treated with a specially designed lithotriptor. In a retrospective study the
      results of this therapy were analysed. The success rate was far better for
      parotid gland calculi than for submandibular calculi. We could not find better
      results than those published in literature with other devices. In our therapeutic
      concept, sialolithotripsy is the therapy of first choice for single parotid gland
      calculi. For submandibular gland calculus this method is advisable in selected
      cases only.

PMID- 15955662
TI  - Peroxiredoxin I expression in tongue squamous cell carcinomas as involved in
      tumor recurrence.
AB  - Peroxiredoxin (Prx) I is an antioxidant protein expressed in proliferating cells.
      We investigated Prx I as marker for tongue cancer status by correlating clinical
      features with Prx I expression. Samples from 132 patients with squamous cell
      carcinoma in the tongue were examined by immunohistochemistry with an anti-Prx I
      antibody. Correlations between Prx I expression and the clinical features of
      tumors were statistically determined using univariate and multivariate analyses.
      Univariate analysis showed Prx I was significantly associated with local
      recurrence (P=0.033). By multiple logistic regression analysis, Prx I expression
      was associated with local recurrence (odds ratio: 2.84; 95% confidence interval:
      1.09-7.43; P=0.034) and lymph node recurrence (odds ratio: 2.86; 95% confidence
      interval: 1.02-8.01; P=0.046). Our results suggested that Prx I expression
      indicates tumors with a high potential for recurrence. Prx I may be used
      clinically to guide treatment for squamous cell carcinoma of the tongue.

PMID- 15955663
TI  - A five-year retrospective study of odontogenic maxillofacial infections in a
      large urban public hospital.
AB  - The aim of this study was to analyze the etiology, presentation, management and
      outcome of odontogenic maxillofacial infections seen in an urban population that
      has only one major public hospital, which is also the only level I trauma center.
      All patients admitted to the Oral and Maxillofacial Surgery Service of San
      Francisco General Hospital with odontogenic infections over a 5-year period were
      included. Age, gender, site of infection, investigations performed, treatment
      carried out and outcomes were studied. Length of hospital stay and any
      readmissions were also noted. A total of 250 patients were admitted with
      maxillofacial infections, and in 157 cases the infection was odontogenic in
      origin. Males outnumbered females (102:55). Children had a preponderance of
      maxillary buccal infections whilst adults had more mandibular infections.
      Hospital stays ranged from 1 to 23 days, and only one patient required re
      admission. A wide range of antibiotics were prescribed and 122 patients required
      dental extractions. Odontogenic maxillofacial infections are a public and
      personal health issue with potential life-threatening complications. This study
      identifies potential risk factors and suggests that early dental extraction,
      incision and drainage, coupled with intravenous antibiotic therapy, is the most
      effective treatment. Antibiotic therapy can be empirical since in no case where
      cultures were performed did this alter the antibiotic management.

PMID- 15955664
TI  - Blindness and visual impairment from severe midface trauma in Nigerians.
AB  - Reports have shown that severe midface trauma causes blindness and visual
      impairment but information from sub-Saharan Africa is sparse. A retrospective
      analysis was carried out of patients who sustained trauma to the midface and
      subsequently lost vision in one or both eyes. There were 25 males and 7 females
      whose ages ranged from 5 to 65 years (mean +/- SD, 33 +/- 13.3 years). All
      patients presented between 1 h and 7 days of sustaining injury (mean +/- SD, 1.9
      +/- 1.9 days). Road traffic accidents (37.5%) and gunshot injuries (34.4%) were
      the commonest causes. Of the 32 patients identified with loss of vision, half
      sustained fractures of the zygomatic complex while a total of 54 soft-tissue and
      bony injuries were recorded. The majority of patients (68.8%) had a ruptured
      globe, followed by vitreoretinal haemorrhage and traumatic optic neuropathy in
      18.7% and 12.5%, respectively. Visual acuity ranged from 6/60 to 'no light
      perception'. Surgical exploration, enucleation, evisceration or exenteration was
      the treatment method used for those with ruptured globes. About 10.8% of patients
      with severe midface trauma also sustained loss of vision in one eye. Loss of
      vision associated with severe midface trauma is most likely to occur with road
      traffic accidents and gunshot injuries. High impact from such incidents often
      causes extensive damage to the eyeball resulting in immediate and irreversible
      blindness.

PMID- 15955665
TI  - Chondroma of the cheek: A case report.
AB  - An extremely rare case of soft tissue chondroma occurring in the right cheek of a
      47-year-old woman is reported. The localized nodular tumor was encapsulated and
      composed of hyalinized cartilage with fine calcifications. Most tumor cells were
      positive for vimentin and S-100 protein, but negative for cytokeratin, factor
      VIII, and smooth muscle actin. It seems likely that the tumor cells arise from
      uncommitted mesenchymal stem cells by metaplastic process.

PMID- 15955666
TI  - Evaluation of different treatments for oroantral/oronasal communications:
      experience of 112 cases.
AB  - This retrospective study analyzed the etiologic factors, location and treatments
      for patients with oroantral or oronasal communications (OAC or ONC). Data
      analysis extended to gender, age, etiology, location, type of treatment and short
      term complications from January 1988 to May 2004. A total of 112 patients with
      101 (90%) OAC and 11 (10%) ONC were included. The main etiology for OAC was tooth
      extraction (95%) with similar prevalence between right (49%) and left (51%) side.
      For ONC, pathological conditions (27%) and exodontia (27%) were the most
      prevalent. For the treatment of OAC, suture was the technique most frequently
      used (60%), followed by buccal fat pad (28%), buccal flap (9%), palatal flap (2%)
      and one dental transplant (1%). For ONC, the following treatments were used:
      suture (46%), buccal flap (36%) and palatal flap (18%). Failure to eliminate the
      communication occurred in six (6%) patients of the OAC group and three (27%) of
      the ONC group. The results confirm that tooth extraction was the most common
      etiologic factor for ONC and OAC. Suture, when the communication was small (3-5
      mm), and the use of a buccal fat pad (100% successful), when a larger
      communication existed (>5 mm), seemed to be the two best choices for treatment.

PMID- 15955667
TI  - Re: Dimitroulis, G: The role of surgery in the management of disorders of the
      temporomandibular joint: a critical review of the literature. Part I. Int J Oral
      Maxillofac Surg 2005;34:107-13.

PMID- 15955668
TI  - Free-grafting of mandibular condyle fractures: clinical outcomes in 10
      consecutive patients.
AB  - "Free-grafting" of the superior segment, either alone or in combination with a
      posterior ramus osteotomy, is occasionally required when managing displaced
      condylar neck fractures. This allows ideal reduction and fixation, but carries
      the risk of proximal segment resorption, possibly requiring secondary
      reconstruction. The purpose of this study was to evaluate the clinical and
      radiographic outcomes of this technique in all patients who underwent this
      procedure during a seven-year period at a tertiary care centre. Ten patients who
      had undergone 11 free graft procedures were included in the study. Three patients
      required secondary costochondral reconstruction due to advanced resorption of the
      free-grafted condylar segment, this occurring from 3 to 9 months following the
      initial trauma surgery. All but one of the remaining patients exhibited varying
      degrees of condylar resorption/flattening radiographically, occurring within the
      first year only. However, no occlusal changes occurred in this group either
      objectively or subjectively during this year or during the subsequent follow-up
      period. The mean inter-incisal opening was 47mm (range 40-56). With the exception
      of one patient that had a non-painful reciprocal click of the treated side, no
      patients demonstrated either objective or subjective signs of TMJ pathology. No
      patients reported dietary limitations, and all reported satisfaction with
      treatment to date. Based on objective and subjective evaluation, free grafting of
      the fractured condylar segment in this patient population had a 70% success rate.
      All failures occurred within 9 months and required secondary costochondral
      reconstruction.

PMID- 15955669
TI  - Reduced anticonvulsant efficacy of valproic acid in dopamine beta-hydroxylase
      knockout mice.
AB  - Valproic acid (VPA) is a widely used treatment for both epilepsy and bipolar
      disorders, although its therapeutic mechanism of action is not fully understood.
      Because norepinephrine (NE) is implicated in seizure susceptibility and affective
      disorders, and given previous findings indicating that VPA can act on the NE
      system, it is possible that NE may mediate some of the therapeutic actions of
      VPA. To test this hypothesis, we measured flurothyl-induced seizure
      susceptibility and severity parameters after both acute and chronic VPA
      treatments in dopamine beta-hydroxylase knockout (Dbh -/-) mice that lack NE. We
      found that the protective effects of acute VPA on seizure susceptibility, as
      measured by latency to first myoclonic jerk, were attenuated in Dbh -/- mice.
      Further, while acute VPA reduced the number of control mice that progressed to
      tonic extension, VPA did not reduce seizure severity in Dbh -/- mice. The
      carryover anticonvulsant effects following cessation of chronic VPA treatment
      were similar in both genotypes. Therefore, we conclude that NE is involved in
      some of the anticonvulsant effects of VPA, especially the effect of acute VPA on
      seizure severity.

PMID- 15955670
TI  - Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive
      care patients with intra-abdominal sepsis.
AB  - This study aimed to investigate whether fluid shifts alter ciprofloxacin
      pharmacokinetics in critically ill patients over time. Patients > or = 18 years,
      with normal renal function, requiring intensive care treatment and parenteral
      antibiotics were enrolled. Group A (22 patients) included patients with
      documented intra-abdominal infections. Group B (18 patients) included patients
      with severe sepsis from other causes. All patients received intravenous
      ciprofloxacin 400 mg every 8 h infused over 60 min. Eight timed blood specimens
      were taken on days 0, 2 and 7. Ciprofloxacin plasma concentrations were
      determined using high performance liquid chromatography. There were no
      significant differences between the pharmacokinetics of the two groups or over
      time. Ciprofloxacin pharmacokinetics in critically ill patients do not change
      over time, and intra-abdominal sepsis does not alter ciprofloxacin
      pharmacokinetic parameters to a greater degree than sepsis from other causes in
      critically ill patients.

PMID- 15955671
TI  - Antileishmanial activity of HIV protease inhibitors.
AB  - The proteasomes of some protozoa are possible targets for chemotherapy.
      Leishmaniasis is a major health problem in human immunodeficiency virus (HIV) co
      infected subjects. Two HIV protease inhibitors (PI), indinavir and saquinavir,
      have been shown to block proteasome functions; we therefore investigated their
      effects on the growth of two Leishmania spp. (Leishmania major and Leishmania
      infantum). After 24 h of treatment, both drugs exhibited a dose-dependent
      antileishmanial activity, with 50% lethal dose (LD50) values of, respectively,
      8.3 microM and 7 microM on L. major; minor activity was observed on L. infantum.
      These results add new in vitro insights into the wide-spectrum efficacy of PI and
      suggest studying their action on amastigote forms of leishmania within
      macrophages in order to validate their potential contribution against
      opportunistic infections in treated seropositive patients.

PMID- 15955672
TI  - Co-trimoxazole and quinolone resistance in Escherichia coli isolated from urinary
      tract infections over the last 10 years.
AB  - Over the last 10 years the treatment of choice for urinary tract infections
      (UTIs) in Turkey has changed from co-trimoxazole to quinolones owing to the rate
      of resistance to co-trimoxazole and its high level of therapeutic failure. The
      resistance ratio of 1939 UTI Escherichia coli from outpatients (1994-2003) was
      evaluated by Kirby-Bauer disc diffusion method for the aforementioned antibiotics
      to determine the change in resistance. The co-trimoxazole resistance ratio
      decreased during this period, with the highest ratio in 1996 (69.3%) and the
      lowest ratio in 2003 (38.5%) (P < 0.001). The lowest resistance ratios occurred
      in 1995 (4.1%) for ofloxacin and in 1996 (5.2%) for ciprofloxacin, and the
      highest resistance ratios occurred in 2002 (25.3% and 27.6%) for ofloxacin and
      ciprofloxacin, respectively (P < 0.001, P < 0.001). These findings emphasise that
      antibiotic usage policies, especially empirical therapies, should be based on
      antimicrobial resistance surveillance studies.

PMID- 15955673
TI  - Antibiotic resistance and class 1 integron patterns of non-typhoidal human
      Salmonella serotypes isolated in Hungary in 2002 and 2003.
AB  - The antibiotic resistance profiles of 5178 Salmonella strains representing 19 non
      typhoidal serotypes isolated from human salmonellosis cases in Hungary in 2002
      and 2003 were analysed for resistance to 10 antibiotic agents. The most frequent
      resistances were to nalidixic acid (Nx), streptomycin (S), tetracycline (Tc),
      ampicillin (Amp) and chloramphenicol (Cm) (ranging from 27% to 13%). Forty-five
      percent of the Salmonella Typhimurium strains were multiple resistant and
      belonged mainly to the definitive phage types 104 and U302. A prevalence of 83
      94% of strains of serotypes S. Infantis, S. Hadar and S. Virchow was observed
      with the NxSTc resistance pattern, sometimes complemented with other resistances.
      Multiple resistance was uncommon in S. Enteritidis; nevertheless, 20% of the
      strains, most of which belonged to phage type 4, were nalidixic acid resistant.
      One strain of S. Typhimurium was found to be resistant to ciprofloxacin. Four S.
      Typhimurium strains were resistant to cefotaxime and produced extended-spectrum
      beta-lactamase. Selected isolates were screened for the presence of class 1
      integrons by polymerase chain reaction (PCR). Nucleotide sequencing of the PCR
      products revealed nine different variable regions. One resistance gene was
      identified in five variable regions (aadA1, aadA2, aadA23, dfrV and pse-1), and
      four variable regions carried two resistance gene cassettes (aadB-catB3, dhfrI
      aadA, dfrA17-aadA5 and oxa-1-aadA1).

PMID- 15955674
TI  - Acidified nitrite as a potential antifungal agent.
AB  - The use of acidified nitrite as a potential antifungal agent was investigated by
      exposing clinical isolates of Candida albicans, Candida glabrata, Candida
      tropicalis, Cryptococcus neoformans, Aspergillus fumigatus and Rhodotorula to
      varying concentrations of acidified nitrite at different pH levels to determine
      the minimal fungicidal concentration after 10 min exposure.

PMID- 15955675
TI  - In vitro antimycobacterial activity of newly synthesised S
      alkylisothiosemicarbazone derivatives and synergistic interactions in combination
      with rifamycins against Mycobacterium avium.
AB  - The antimycobacterial activities of two new S-alkylisothiosemicarbazone
      derivatives (1i and 1f) against 32 Mycobacterium avium isolates were
      investigated. The minimum inhibitory concentrations (MICs) were significantly
      lower than those of rifampicin and other reference drugs. The two derivatives
      also showed excellent intracellular activity against M. avium residing in the
      macrophage-like J774 cells. Interestingly, the combination of subinhibitory
      concentrations of 1i and rifabutin or rifampicin induced a potent synergistic
      effect, as determined by the fractional inhibitory concentration indexes (FICIs)
      ranging between 0.103 and 0.412. Such synergistic effect resulted in a 81-fold
      and 139-fold reduction of the MICs of rifabutin and rifampicin, respectively.
      Enhancement of intracellular activity of rifabutin by the S
      alkylisothiosemicarbazone derivative 1i was also observed. Results indicate that
      S-alkylisothiosemicarbazones can be useful in the therapy and prophylaxis of M.
      avium infections and can represent a template for the development of novel
      antimycobacterial drugs. Furthermore, as a consequence of their ability to
      enhance the activity of rifamycins, a reduction of drug interactions following
      the co-administration of protease inhibitors could be achieved by lower doses of
      rifampicin and rifabutin.

PMID- 15955676
TI  - Prevalence of dementia in the elderly in Europe.
AB  - Dementia is an important public health problem as it is one of the most common
      diseases in the elderly and a major cause of disability and mortality. This
      review on dementia is restricted to European Union countries where the
      overwhelming majority of studies have been undertaken, and will also refer to the
      EURODEM publications which may be considered to be the principal European
      reference point in this area. In subjects aged over 65, crude prevalence rates
      for dementia varied between 5.9% and 9.4%. We discuss the major problems limiting
      the use of these estimations, limits which may differ according to the area of
      application, be it etiological research or care provision.

PMID- 15955677
TI  - Problematic drug use and drug use disorders in EU countries and Norway: an
      overview of the epidemiology.
AB  - OBJECTIVE: To estimate the prevalence of drug use disorders in the European Union
      and Norway. METHOD: Based on a systematic literature search and an expert survey,
      publications after 1990 on prevalence of drug use disorders (DUD, defined as drug
      dependence and drug abuse or harmful use) in EU countries and Norway were
      reviewed. The search included both direct estimations based on general population
      surveys using the DSM-IIIR, DSM-IV, or ICD-10 definitions of DUD; and indirect
      estimates based on other epidemiological methods, such as multiplier procedures
      based on treatment or legal data and capture-recapture techniques. The indirect
      methods did not use diagnostic criteria, but criteria based on duration and
      pattern of use, labelled as problematic drug use as a meaningful approximation.
      RESULTS: The majority of DUD as estimated from direct methods using general
      population surveys were cannabis use disorders, usually not included in indirect
      estimates. The prevalence of thus defined disorders can be as high as 3%. For
      disorders other than cannabis use disorders (i.e. opioid, cocaine and amphetamine
      use disorders), indirect estimates of prevalence were consistently higher than
      those based on direct estimates, and ranged between 0.3% and 0.9% in European
      Union countries and Norway. Men have higher prevalence rates of DUD than women,
      but the difference was much less pronounced in general population surveys.
      Younger age (18-25 years) is the age group with the highest estimates.
      CONCLUSION: General population surveys typically result in a serious
      underestimation of the prevalence of DUD other than cannabis use disorders,
      because many people with DUD are not reached by these surveys (hidden
      populations). Based on the more valid indirect estimates, it is concluded that
      problem drug use constitutes a relatively high burden of disease and social
      problems in Europe.

PMID- 15955678
TI  - Effects of RM-beta-CD on sublingual bioavailability of Delta9
      tetrahydrocannabinol in rabbits.
AB  - The purpose of the present study was to develop novel cyclodextrin-containing
      sublingual formulations of cannabinoids. Complexation of model cannabinoids,
      Delta(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD), with randomly
      methylated beta-cyclodextrin (RM-beta-CD) and hydroxypropyl-beta-cyclodextrin (HP
      beta-CD), were studied by the phase-solubility method. Due to better complexation
      efficiency, RM-beta-CD was selected for further studies. Solid THC/RM-beta-CD and
      CBD/RM-beta-CD complexes were prepared by freeze-drying. The dissolutions of both
      THC and CBD in the presence and absence of RM-beta-CD were determined. THC was
      selected for in vivo studies: the pharmacokinetics of THC after both sublingual
      and oral administrations of ethanolic THC and THC/RM-beta-CD complex solutions
      were studied in rabbits. The aqueous solubility of CBD and THC increased as a
      function of CD concentration, showing A(L)- and A(P)-type diagrams for HP-beta-CD
      and RM-beta-CD, respectively. Dissolution rates of THC/RM-beta-CD and CBD/RM-beta
      CD complexes were significantly (p < 0.05) higher than those of plain THC and
      plain CBD, respectively. The absolute bioavailability (F) of THC decreased in the
      following order: sublingual THC/RM-beta-CD solution (F = 12.1+/-1.4%; mean+/
      S.D.; n = 4) > oral THC/RM-beta-CD solution (F = 4.0+/-6.0%) > or = sublingual
      ethanolic THC solution (F = 3.8+/-2.8%) > oral ethanolic THC solution (F = 1.3+/
      1.4%). These results demonstrate that RM-beta-CD increases both the aqueous
      solubility and dissolution rate of these cannabinoids, making the development of
      novel sublingual formulation possible. These results also suggest that the
      sublingual administration of a THC/RM-beta-CD complex substantially increases the
      bioavailability of THC in rabbits.

PMID- 15955679
TI  - Insights into structure-activity relationships from lipophilicity profiles of
      pyridin-2(1H)-one analogs of the cardiotonic agent milrinone.
AB  - The pH-dependent distribution profiles of a series of pyridin-2(1H)-one analogs
      of the inotropic/vasodilator agent milrinone, determined in 1-octanol/water (and
      for a number of them also in chloroform-water) using a pH-metric technique,
      showed that partition coefficients of the neutral forms (logP(N)) significantly
      encode for 2-pyridone/2-hydroxypyridine tautomerism. A comparison between
      experimental and calculated logP (CLOG P) values indicated that electron
      withdrawing substituents, at the C(6) position, and to a lesser extent at the
      C(3) and C(5) positions, push up logPs toward the values of the more lipophilic 2
      hydroxypyridine tautomers. RP-HPLC parameters (log k'omega) carry for large part
      similar information related to tautomerism-dependent lipophilicity, but they were
      also found to reasonably correlate with the solute molar volumes (r2 = 0.75).
      Investigating the implications of ionization and partition properties in
      modulating the in vitro cardiotonic activity of the examined compounds revealed
      that a high fraction of the neutral species at physiological pH, predominantly in
      the more polar pyridone (OX) tautomer, increases the positive inotropic potency.

PMID- 15955680
TI  - Geometric mean ratio-dependent scaled bioequivalence limits with leveling-off
      properties.
AB  - In this study, novel approaches for the design of bioequivalence (BE) limits are
      developed. The new BE limits scale with intrasubject variability but only until a
      geometric mean ratio (GMR)-dependent plateau value and combine the classic (0.80
      1.25) and expanded (0.70-1.43) BE limits into a single criterion. Plots of the
      extreme GMR values accepted as a function of coefficient of variation (CV) have a
      convex shape, similar to the classic unscaled 0.80-1.25 limits. The performance
      of the novel approaches in comparison to the classic unscaled 0.80-1.25 limits as
      well as the two expanded BE limits, i.e., 0.70-1.43 and 0.75-1.33 was assessed
      using simulated data. Two-period crossover BE investigations with 12, 24 or 36
      subjects were simulated with assumptions of CV 10%, 20%, 30% or 40%. At low CV
      values, the performance of the novel BE limits is almost identical to the 0.80
      1.25 criterion. On the contrary, the expanded BE limits are very permissive even
      at high GMR values. For high CV% values (30% and 40%), the new BE limits show a
      much greater probability of declaring BE when GMR = 1 in comparison to the
      classic 0.80-1.25 limits. In addition, when the drug products differ more than
      25%, the new BE limits show much lower percentage of acceptance than the expanded
      0.70-1.43 limits. One of the major advantages of the new BE limits is their
      gradual expansion with variability until a GMR-dependent plateau value. Finally,
      the continuity and leveling-off properties of the new BE limits make them
      suitable for the assessment of BE studies, irrespective of the level of
      variability encountered.

PMID- 15955681
TI  - Initial characterization of the microenvironment that regulates connective tissue
      degradation in amniochorion during normal human labor.
AB  - Extracellular matrix degradation in fetal membranes leading to its rupture is
      coupled to myometrial activity and cervical ripening during human normal labor.
      Mechanisms which modulate collagen degradation in amniochorion during labor have
      not been elucidated. Initial characterization of the effect of different blood
      compartments on connective tissue degradation in amniochorion during human labor
      was explored. Amniochorion explants were stimulated with plasma of maternal
      venous blood, umbilical cord blood or placental blood, obtained from women with
      pregnancies at term, with or without labor. MMP-2 and MMP-9 activities were
      quantified in conditioned media by gelatin-zymography as an index of connective
      tissue degradation. Collagen content was measured in tissue explants and collagen
      fibrils distribution was examined by electron microscopy. Placental plasma from
      term pregnancies, with or without labor, is enriched with soluble signals that
      enhance the in vitro MMP-9 production by amniochorion. Accompanying
      ultrastructural distortion of collagen fibers and demonstration of collagen
      degradation fragments confirmed induction of extracellular matrix degradation.
      Control experiments in which MMP-9 activity was blocked with TIMP-1 resulted in
      inhibition of all the above mentioned changes. These results suggest that
      placental intervillous space is a functional compartment in which mediators
      capable to induce collagen degradation in amniochorion are selectively expressed
      during human labor.

PMID- 15955682
TI  - Alarmins: chemotactic activators of immune responses.
AB  - The recruitment and activation of antigen-presenting cells are critical early
      steps in mounting an immune response. Many microbial components and endogenous
      mediators participate in this process. Recent studies have identified a group of
      structurally diverse multifunctional host proteins that are rapidly released
      following pathogen challenge and/or cell death and, most importantly, are able to
      both recruit and activate antigen-presenting cells. These potent
      immunostimulants, including defensins, cathelicidin, eosinophil-derived
      neurotoxin, and high-mobility group box protein 1, serve as early warning signals
      to activate innate and adaptive immune systems. We propose to highlight these
      proteins' unique activities by grouping them under the novel term 'alarmins', in
      recognition of their role in mobilizing the immune system.

PMID- 15955683
TI  - Immunological techniques: ex vivo characterization of T cell-mediated immune
      responses in cancer.

PMID- 15955684
TI  - Host-pathogen interactions in the 21st century.

PMID- 15955685
TI  - Molecular tracking of antigen-specific T-cell clones during immune responses.
AB  - Despite extended international efforts, the mechanisms governing T-cell receptor
      repertoire selection and kinetics in response to foreign or tumour antigens
      remain poorly characterized. A central goal of current research is to develop
      improved, reliable, immunological monitoring methods that measure and combine
      such parameters as the frequency of antigen-specific T cells and their functional
      capacities, as well as their clonal expansion during immune responses. Detecting
      and tracking defined anti-viral- and anti-tumour-specific T-cell responses ex
      vivo should lead to improvements in therapeutic strategies against viral
      infection or cancer in the future. During the past few years, highly sensitive
      tools have been developed to enable the molecular dissection and tracking of
      clonal T-cell expansion in animal models as well as in humans.

PMID- 15955686
TI  - Viral and host factors in the pathogenesis of HIV infection.
AB  - Recent studies suggest that the pathogenesis of HIV infection and AIDS involves
      two distinct phases. During acute infection, massive depletion of CD4+CCR5+
      memory T cells within the mucosal-associated lymphoid tissue leads to major and
      potentially irreversible damage to CD4+ T-cell-mediated immune functions. The
      emergence of potent, but ultimately ineffective, cell-mediated and humoral
      responses to HIV leads to the chronic phase of infection, which is characterized
      by partial control of viral replication, chronic immune activation, progressive
      decline of the naive and memory T-cell pool, and systemic CD4+ T-cell depletion.
      The identification of these two pathogenic phases of HIV infection could have
      important implications in terms of HIV therapy and vaccine development.

PMID- 15955687
TI  - Pathogenesis of viral hemorrhagic fever.
AB  - Single-stranded RNA viruses from four different families cause a syndrome of
      fever and malaise, 'capillary leak' with loss of plasma volume, and coagulation
      defects which can lead to bleeding. Although direct cytopathic effects can
      contribute to disease severity, most features of illness are caused by innate
      immune responses, as the systemic spread of virus to macrophages and dendritic
      cells leads to the release of mediators that modify vascular function and have
      procoagulant activity. The synthesis of tissue factor by infected cells can also
      trigger coagulation. Failure of adaptive immunity through impaired dendritic cell
      function and lymphocyte apoptosis can have a crucial role in fatal infection.

PMID- 15955688
TI  - Cochrane systematic reviews of treatments for lung cancer.
AB  - Morbidity and mortality from lung cancer is a major burden to global health. The
      integration of expert clinical experience, patient preference and high-quality
      evidence, including Cochrane systematic reviews, can only help improve outcomes
      from this highly lethal condition.

PMID- 15955689
TI  - Effect of protein orientation on electron transfer between photosynthetic
      reaction centers and carbon electrodes.
AB  - A new type of monolayer of photosynthetic reaction centers (RC) with the primary
      donor facing the carbon electrode has been constructed using a new bifunctional
      linker and genetically engineered protein. Comparison of protein in two different
      orientations with linkers binding to the opposite sides of the protein
      demonstrates the possibility of utilizing the constructed surfaces as
      photoelectronic devices. The results show improvement of the electron transfer
      efficiency when RC is bound with the primary donor (P) facing the electrode (P
      side). In either protein orientation, electron transfer within the protein is
      unidirectional and when applying a voltage RC operates as a photorectifier.
      Electron transfer between the protein and carbon electrodes in the constructed
      devices is most likely occurring by tunneling.

PMID- 15955690
TI  - A prospective study on predictive factors linked to the presence of BRCA1 and
      BRCA2 mutations in breast cancer patients.
AB  - We prospectively screened a hospital-based population of 1000 successive breast
      cancer patients receiving adjuvant radiotherapy for predictive factors associated
      with the presence of BRCA1 and BRCA2 mutations. We offered genetic counseling and
      DNA analysis to selected patients. About 52% of patients showed at least one
      presumed predictive factor. Hundred and thirty-seven patients underwent DNA
      analysis. We identified 14 deleterious mutations (10.2%, 95% CI: 5.2-15.3%): 8
      BRCA1 mutations and 6 BRCA2 mutations and 14 variants of uncertain clinical
      significance. Ovarian cancer in the family history was the only factor
      significantly associated with the presence of a disease-causing mutation (P <
      0.01). Eight of the 14 (57%) mutation carriers had no affected first-degree
      relatives and in 4 of these there was no family history of breast or ovarian
      cancer. Clinicians should offer genetic counseling and DNA testing to breast
      cancer patients from families with breast and ovarian cancer, and to patients who
      are younger than 45 years when they are diagnosed with breast cancer.

PMID- 15955691
TI  - Full-length sequence and expression analysis of estrogen receptor alpha mRNA in
      feline mammary tumors.
AB  - We report here on the isolation and sequencing of feline estrogen receptor alpha
      (ER-alpha) mRNA. Feline ER-alpha showed three alternative 5' untranslated exons
      and a common transcript of 6183 base pairs (bp). The putative coding sequence
      (1788 bp) and the unusually long 3' untranslated (3'-UTR) region (4305 bp)
      displayed high sequence similarity with human ER-alpha. A highly conserved
      sequence block was found in the 3'-UTR corresponding to a putative regulatory
      element for mRNA stability. In addition to wild-type ER-alpha mRNA, several exon
      deleted splicing variants (ERDeltaE2, ERDeltaE3, ERDeltaE4, ERDeltaE5, ERDeltaE6,
      ERDeltaE7) were found in various feline tissues. This is similar to what observed
      in human tissues and opposite to the near absence of exon-deleted isoforms in
      rodents. Expression analysis of exon-deleted variants was also conducted on 24
      samples of feline mammary carcinoma (FMC) and 15 normal mammary gland (NMG)
      controls, using a "splice targeted approach". The prevalence of some variants was
      similar for human and feline ER-alpha, while other isoforms were expressed at
      different frequencies in the two species. Two of the most frequent isoforms
      (ERDeltaE4, ERDeltaE7) were significantly less frequent in FMCs than in NMGs,
      likely as a consequence of decreased expression of ER-alpha in FMCs.

PMID- 15955692
TI  - Analysis of spatiotemporal regulation of aromatase in the brain using transgenic
      mice.
AB  - Brain aromatase is widely distributed in the vertebrates, from fish to mammals,
      and plays important roles in functional reproductive behavior through production
      of estrogen as a neurosteroid. It is expressed only in the nerve cells of
      specific brain regions with a transient peak in the neonatal period when sexual
      behavior becomes organized, and therefore provides a good model system to study
      regulatory mechanism of cell-specific, brain region-specific, and developmental
      stage-specific expression. To elucidate spatiotemporal regulation of brain
      aromatase, we prepared transgenic mice carrying a reporter gene under the
      promoter of brain-specific exon 1f of the mouse aromatase gene. The reporter
      transgene carrying a 6.5 kb upstream region of the brain-specific promoter
      accurately reproduced the spatiotemporal expression patterns of aromatase in
      mouse brain, whereas transgenes carrying smaller fragments of the promoter showed
      ambiguous or inconsistent expression patterns. The binding sites of Aro-AI, Aro
      AII, and Aro-B for nuclear factors were also identified in the proximal region of
      the exon 1f brain-specific promoter. Introduction of a mutation into the Aro-AII
      site in the reporter transgene carrying -6.5 kb promoter region of exon 1f caused
      complete alteration of the spatiotemporal expression pattern of the reporter gene
      in the transgenic mice. These results indicate that the -6.5 kb promoter region
      of exon 1f is the minimal essential element for brain-specific regulation, with
      both proximal and distal promoter regions required for accurate spatiotemporal
      expression of aromatase in the mouse brain.

PMID- 15955693
TI  - Aromatase inhibitors--socio-economical issues.
AB  - Novel, third-generation aromatase inhibitors are currently implemented for
      treatment of postmenopausal breast cancer in the metastatic and adjuvant setting
      and, potentially, for breast cancer prevention. Introduction of novel therapeutic
      strategies to large patient groups may add significant costs to health care
      budgets, forcing institutions to focus entirely on costs or the cost-utility of
      implementing such novel strategies. Breast cancer is the most frequent cancer in
      the female population in western societies, and its incidence is currently
      increasing in other parts of the world as well. Due to the proven efficacy and
      limited side effects of endocrine therapy in the adjuvant setting, the
      indications for use have been successively broadened. Currently, the majority of
      postmenopausal women treated for an estrogen-receptor positive breast cancer will
      be offered adjuvant endocrine therapy; thus, a general change of practice may
      cause significant implications to healthcare costs. This may relate to direct
      drug costs as well as indirect costs related to prevention of side effects, like
      additional use of bisphosphonates to prevent enhanced bone loss. The aim of this
      paper is to overview these considerations and put them into perspective by simple
      illustrations taken from current cost estimates.

PMID- 15955694
TI  - Synthesis of free and sulphoconjugated 16-androstene steroids by the Leydig cells
      of the mature domestic boar.
AB  - This study examined the involvement of sulphoconjugation in the biosynthesis of
      the 16-androstene steroids in Leydig cells of the mature boar, since the
      formation of steroid sulphoconjugates can reduce the levels of these steroids
      that accumulate in fatty tissue. Leydig cells were purified from testes of mature
      male pigs and incubated with pregnenolone, or various individual 16-androstene
      steroids for 10 min, 1, 4 and 8h. Sulphoconjugated steroids were recovered by
      solid-phase extraction followed by solvolysis. Profiles of unconjugated and
      sulphoconjugated steroids were analysed by HPLC. Steroids present in the
      sulphoconjugated fractions were purified, derivatised as O
      methoxime/trimethylsilyl ethers (MO-TMS), and subsequently identified using gas
      chromatography-mass spectrometry (GC-MS). The principal metabolite produced from
      incubations with pregnenolone, androstadienol, androstadienone and 5alpha
      androstenone was 3beta-androstenol. 16-Androstene steroids that were
      sulphoconjugated included 5alpha-androstenone, 3beta-androstenol and 3alpha
      androstenol. Approximately 70% of the total amount of each 16-androstene steroid
      was in its sulphoconjugated form after incubations for 4h or more. The finding
      that sulphoconjugated 5alpha-androstenone was present in large amounts suggests
      that this steroid may be converted from a 3-keto to a 3-enol form which is
      subsequently sulphoconjugated. These findings emphasise the need to consider the
      impact of sulphoconjugation of the 16-androstene steroids and their role in
      contributing to boar taint.

PMID- 15955695
TI  - Positive and negative transcriptional regulation of aromatase expression in human
      breast cancer tissue.
AB  - By performing primer-specific RT-PCR analyses, three laboratories including ours
      have found that exons I.3 and PII are the two major exon Is present in aromatase
      mRNAs isolated from breast tumors. These results suggest that promoters I.3 and
      II are the major promoters directing aromatase expression in breast tumors. The
      characterization of transcription factors that interact with the two elements
      near promoters I.3 and II, i.e., S1 and CREaro, helps us better understand the
      mechanism of the switch of promoter usage between normal breast tissue and cancer
      tissue. The positions of the two regulatory regions were mapped by DNase I
      footprinting and DNA deletion analyses. We applied the yeast one-hybrid approach
      to screen a human breast tissue hybrid cDNA expression library for genes encoding
      the proteins binding to these regions. Our results suggest that in normal breast
      tissue, the function of promoters I.3 and II is suppressed through the binding of
      EAR-2, COUP-TFI, and RARgamma to S1, and through the binding of Snail/Slug
      proteins to their binding site that quenches the CREaro activity. In cancer
      tissue, the expression levels of EAR-2, COUP-TF1, EARgamma, Snail, and Slug
      decrease, and aromatase expression is then up-regulated through the binding of
      ERRalpha to S1 and the binding of CREB1 or related factors to CREaro. In a
      separate study, we found that estrogen could up-regulate aromatase expression in
      breast cancer cells by a non-genomic action of ERalpha via cross-talk with growth
      factor-mediated pathways. Our preliminary results suggest that protein kinase C
      delta participates in this ERalpha-growth factor mediated regulation. To further
      understand the regulatory mechanism, we have recently initiated an in vivo
      footprinting analysis of the -260/+76 bp region of promoter I.3. The experiments
      were conducted with both MCF-7 and MDA-MB-231 breast cancer cells. Our results
      revealed several footprinted sites. Five regions (sites 1-5) were then selected
      for functional analysis through DNA site-directed mutagenesis experiments. This
      analysis has also confirmed the promoter I.3 TATA site and Snail/Slug binding
      site. These mutants showed higher luciferase activity when compared to the wild
      type, indicating that the proteins binding to these sites were acting as
      repressors. By reviewing findings from our laboratory and other laboratories, a
      detailed mechanism for the transcriptional regulation of aromatase expression in
      breast cancer tissue is summarized and discussed.

PMID- 15955696
TI  - Estrogen receptor alpha is required for mammary development and the induction of
      mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice.
AB  - Aromatase transgenic mice exhibit hyperplastic and dysplastic changes, attesting
      to the importance of local estrogen in breast carcinogenesis. These mice also
      show increased levels of the estrogen receptor alpha and beta (ERalpha, ERbeta)
      suggesting that this receptor may play an important role in the initiation of
      estrogen-mediated mammary hyperplasia observed in these mice. To address the
      specific role of ERalpha in the mammary development and in the induction of
      estrogen-mediated hyperplasia in aromatase transgenic mice, we have generated
      MMTV-aromatase x ERalpha knockout cross (referred as aromatase/ERKO). Even though
      ERbeta is expressed in aromatase/ERKO mice, lack of ERalpha leads to impaired
      mammary growth in these mice. The data suggest that ERalpha plays an important
      role in the mammary gland development as well as in the induction of mammary
      hyperplasia in aromatase transgenic mice. Lack of ERalpha expression in the
      aromatase/ERKO mice resulted in a decrease in the expression of Cyclin D1, PCNA
      and TGFbeta relative to the aromatase parental strain. The studies involving
      aromatase/ERKO mice show that lack of ERalpha results in impaired mammary
      development even in the presence of continuous tissue estrogen, suggesting
      estrogen/ERalpha-mediated actions are critical for mammary development and
      carcinogenesis.

PMID- 15955697
TI  - Synthesis and biological evaluation of benzothiazole derivatives as potent
      antitumor agents.
AB  - Based on 2-methyl-4-nitro-2H-pyrazole-3-carboxylic acid[2
      (cyclohexanecarbonylamino)benzothiazol-6-yl]amide (1), which shows selective
      cytotoxicity against tumorigenic cell lines, 2,6-dichloro-N-[2
      (cyclopropanecarbonylamino)benzothiazol-6-yl]benzamide (13b) was designed and
      synthesized as a biologically stable derivative containing no nitro group. The
      highly potent derivative 13b exhibited excellent in vivo inhibitory effect on
      tumor growth.

PMID- 15955698
TI  - The identification, synthesis, protein crystal structure and in vitro biochemical
      evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors.
AB  - High-throughput screening identified the 3,4-diarylpyrazole CCT018159 as a novel
      and potent (7.1 microM) inhibitor of Hsp90 ATPase activity. Here, we describe the
      synthesis of CCT018159 and a number of close analogues together with data on
      their biochemical properties. Some initial structure-activity relationships are
      discussed, as well as the crystal structure of CCT018159 bound to Hsp90.

PMID- 15955699
TI  - (1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-ylamine derivatives: further
      optimisation as highly potent and selective MSK-1-inhibitors.
AB  - The novel imidazo[4,5-c]pyridine 1,2,5-oxadiazol-3-yl template affords an
      excellent start point for identification of inhibitors of a number of protein
      kinases. Here we report on its optimisation for mitogen and stress-activated
      protein kinase-1 (MSK-1) inhibitory activity, and selectivity over other kinases.

PMID- 15955700
TI  - A family with a novel frameshift mutation in the PMP22 gene (c.433_434insC)
      causing a phenotype of hereditary neuropathy with liability to pressure palsies.
AB  - Hereditary neuropathy with liability to pressure palsies is usually due to PMP22
      deletion. Point mutations of PMP22 causing an hereditary neuropathy with
      liability to pressure palsies phenotype are rare. We describe a clinical and
      electrodiagnostic phenotype of hereditary neuropathy with liability to pressure
      palsies in a 21-year-old woman, which led to our detecting a novel frameshift
      mutation of PMP22. This mutation was also found in her mother and brother and
      corresponded to an insertion of one cytidine between nucleotides 433 and 434 in
      the last coding exon (c.433_434insC). The mutated PMP22 protein lacks the last 15
      amino acids and has a modified C terminus lengthened to 221 residues instead of
      160 (Leu145fsX222). The mother and the proband had a clinical and
      electrophysiological hereditary neuropathy with liability to pressure palsies
      phenotype. The brother was asymptomatic, but the results of electrodiagnostic
      tests were suggestive of hereditary neuropathy with liability to pressure
      palsies. This observation of a new mutation mostly leading to a PMP22
      haploinsufficiency provides further evidence of the diversity of phenotypes
      associated with frameshift PMP22 mutations.

PMID- 15955701
TI  - Automated feature assessment in instrumented gait analysis.
AB  - A methodological modular framework is presented for automated assessment of gait
      patterns. The processing steps of data selection, gait parameter calculation and
      evaluation are not limited to a specific field of application and are largely
      independent of case-based clinical expert knowledge. For these steps, a variety
      of mathematical methods was used and the validity of the approach to assess gait
      parameters tested by applying it to the clinical problem of Botulinum Toxin A
      (BTX-A) treatment of the spastic equinus foot. A set of 3670 parameters was
      ranked by relevance for classification of a group of 42 diplegic cerebral palsy
      (CP) patients and an age-matched reference group. The same procedure was
      performed for pre- and post-therapeutic data sets of these patients. Gait
      parameters of high relevance coincided well with results of previous studies
      based on partly manual and more subjective parameter selection. A norm distance
      measure is introduced to facilitate the quantification of deviations from a
      normal walking pattern and can be used as an overall scalar measure to evaluate
      differences in gait patterns or as a set of measures attributing each joint angle
      separately.

PMID- 15955702
TI  - Recent advances in tumor-targeting anticancer drug conjugates.
AB  - Traditional cancer chemotherapy relies on the premise that rapidly proliferating
      cancer cells are more likely to be a killed by cytotoxic agent. In reality,
      however, cytotoxic agents have very little or no specificity, which leads to
      systemic toxicity, causing severe undesirable side effects. Therefore, various
      drug delivery protocols and systems have been explored in the last three decades.
      Tumor cells overexpress many receptors and biomarkers, which can be used as
      targets to deliver cytotoxic agents into tumors. In general, a tumor-targeting
      drug delivery system consists of a tumor recognition moiety and a cytotoxic
      warhead connected directly or through a suitable linker to form a conjugate. The
      conjugate, which can be regarded as 'prodrug', should be systemically non-toxic.
      This means that the linker must be stable in circulation. Upon internalization
      into the cancer cell the conjugate should be readily cleaved to regenerate the
      active cytotoxic agent. Tumor-targeting conjugates bearing cytotoxic agents can
      be classified into several groups based on the type of cancer recognition
      moieties. This review describes recent advances in tumor-targeting drug
      conjugates including monoclonal antibodies, polyunsaturated fatty acids, folic
      acid, hyaluronic acid, and oligopeptides as tumor-targeting moieties.

PMID- 15955703
TI  - Synthesis and antitubercular activities of bis-glycosylated diamino alcohols.
AB  - Conjugate addition of diamines to glycosyl olefinic esters 1a and 1b followed by
      reduction of resulting bis-glycosyl beta-amino esters (2-7 and 14-19) with
      lithium aluminium hydride led to the respective glycosyl amino alcohols (8-13 and
      20-25) in moderate to good yields. All the compounds were evaluated for
      antitubercular activity against Mycobacterium tuberculosis H(37)Ra and H(37)Rv.
      Few of the compounds exhibited antitubercular activity with MIC as low as 6.25
      3.12microg/mL in virulent and avirulent strains. Compound 13 was found to be
      active against MDR strain and showed mild protection in mice.

PMID- 15955704
TI  - (83m)Kr radioactive source based on (83)Rb trapped in cation-exchange paper or in
      zeolite.
AB  - The mono-energetic conversion electrons from the decay of (83m)Kr represent a
      unique tool for energy calibration and systematic studies of the tritium beta
      spectrum measured in neutrino mass determination experiments. For this reason,
      the corresponding parent isotope was produced in reactions (nat)Kr(p,xn)(83)Rb.
      The behaviour of (83)Rb (T(1/2)=86.2d) and its daughter product (83m)Kr
      (T(1/2)=1.83h) was examined, when the (83)Rb was trapped in a cation-exchanger
      chromatographic paper or in zeolite. Using gamma spectroscopy measurements,
      recommendations for the production of a (83)Rb/(83m)Kr radionuclide generator
      based on these cation-exchangers and suitable for the neutrino mass determination
      experiment KATRIN were deduced.

PMID- 15955705
TI  - A new method for radiochemical separation of arsenic from irradiated germanium
      oxide.
AB  - Radioarsenic labelled radiopharmaceuticals could be a valuable asset to Positron
      Emission Tomography (PET). In particular, the long half-lives of (72)As
      (T(1/2)=26 h) and (74)As (T(1/2)=17.8 d) allow to investigate slow physiological
      or metabolical processes, like the enrichment and distribution of antibodies in
      tumor tissue. This work describes the direct production of no-carrier-added (nca)
      arsenic isotopes *As, with *=71, 72, 73, 74 or 77, the reaction to [*As]AsI(3)
      and its radiochemical separation from the irradiated solid germanium oxide via
      polystyrene-based solid-phase extraction. The germanium oxide target, irradiated
      at a cyclotron or a nuclear reactor, is dissolved in concentrated HF and Ge is
      separated almost quantitatively (99.97%) as [GeF(6)](2-). [*As]AsI(3) is formed
      by addition of potassium iodide. The radiochemical separation yield for arsenic
      is >90%. [*As]AsI(3) is a versatile radioarsenic labelling synthon.

PMID- 15955706
TI  - Chronic treatment with agents that stabilize cytosolic IkappaB-alpha enhances
      survival and improves resting membrane potential in MDX muscle fibers subjected
      to chronic passive stretch.
AB  - The potential pathogenic role of increased NFkappaB signaling in passively
      stretched dystrophic skeletal muscle was examined by treating adult mdx mice with
      an agent that stabilized cytosolic IkappaB-alpha (pyrollidine dithiocarbamate,
      PDTC)and examining the effects of this treatment on the chronically stretched mdx
      triangularis sterni (TS) muscle. Daily PDTC treatment significantly increased the
      number of surviving striated TS fibers regardless of age. TS fibers from
      untreated mdx mice had significantly lower resting potentials (RPs) than
      nondystrophic mice. Treatment with GdCl3 to block resting Ca2+ influx had no
      effect on RP in either nondystrophic or mdx preparations. Daily treatment with
      PDTC significantly improved the RP regardless of age. These results are
      consistent with the hypothesis that passive stretch activates an NFkappaB
      mediated pathogenic mechanism in dystrophic muscle and suggest that agents which
      stabilize cytosolic IkappaB-alpha levels may be useful for treating Duchenne and
      related muscular dystrophies.

PMID- 15955709
TI  - Relation between insulin resistance and serum concentrations of IL-6 and TNF
      alpha in overweight or obese women with early stage breast cancer.
AB  - Insulin resistance (IR) and obesity may be risk factors for breast cancer. The
      mechanism of IR in patients with cancer has not been fully clarified yet. This
      study was conducted to evaluate the possible role of circulating cytokines; tumor
      necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6) in inducing IR in 20
      overweight or obese patients with early stage breast cancer and to compare their
      levels with that of body mass index matched 20 healthy controls. IR was
      calculated by homeostasis model assessment (HOMA) method. Four groups were formed
      according to a 2.7 HOMA-IR cut-off value as breast cancer with or without IR and
      controls with or without IR. IL-6 and HOMA-IR values were found to be higher in
      breast cancer patients with IR compared to other groups. There was no significant
      difference in TNF-alpha levels between groups. HOMA-IR values correlated with
      estradiol and IL-6 levels in all breast cancer patients but not TNF-alpha. HOMA
      IR values, serum insulin, estradiol and IL-6 levels in the receptor positive
      group were significantly higher than those of the receptor negative group. These
      results suggested a possible contribution of endogenous IL-6 production and
      hyperinsulinemia to the development of breast cancer in overweight or obese
      patients with prominent IR.

PMID- 15955711
TI  - Dendritic cell heterogeneity: developmental plasticity and functional diversity.

PMID- 15955712
TI  - Monocyte-derived dendritic cells.
AB  - It has been recently demonstrated that, in addition to function as macrophage
      precursors, monocytes have the capacity to differentiate into dendritic cells
      (DCs), and therefore they play an essential role in both the innate and adaptive
      immunity. Monocytes display a remarkable functional diversity, allowing them to
      perform multiple defense functions, from pathogen elimination by phagocytosis, to
      the induction of antigen-specific T cell responses. This functional potential
      relies essentially in their developmental plasticity, permitting monocytes to
      differentiate into different subsets of macrophages and DCs. Although recent data
      suggest that the acquisition of functional specialization by monocytes is
      controlled by chemotactic, activation and differentiation factors, how monocyte
      differentiation occurs under physiological conditions remains largely unknown.

PMID- 15955710
TI  - Gene expression profiling of serum- and interleukin-1 beta-stimulated primary
      human adult articular chondrocytes--a molecular analysis based on chondrocytes
      isolated from one donor.
AB  - In order to understand the cellular disease mechanisms of osteoarthritic
      cartilage degeneration it is of primary importance to understand both the
      anabolic and the catabolic processes going on in parallel in the diseased tissue.
      In this study, we have applied cDNA-array technology (Clontech) to study gene
      expression patterns of primary human normal adult articular chondrocytes isolated
      from one donor cultured under anabolic (serum) and catabolic (IL-1beta)
      conditions. Significant differences between the different in vitro cultures
      tested were detected. Overall, serum and IL-1beta significantly altered gene
      expression levels of 102 and 79 genes, respectively. IL-1beta stimulated the
      matrix metalloproteinases-1, -3, and -13 as well as members of its intracellular
      signaling cascade, whereas serum increased the expression of many cartilage
      matrix genes. Comparative gene expression analysis with previously published in
      vivo data (normal and osteoarthritic cartilage) showed significant differences of
      all in vitro stimulations compared to the changes detected in osteoarthritic
      cartilage in vivo. This investigation allowed us to characterize gene expression
      profiles of two classical anabolic and catabolic stimuli of human adult articular
      chondrocytes in vitro. No in vitro model appeared to be adequate to study overall
      gene expression alterations in osteoarthritic cartilage. Serum stimulated in
      vitro cultures largely reflected the results that were only consistent with the
      anabolic activation seen in osteoarthritic chondrocytes. In contrast, IL-1beta
      did not appear to be a good model for mimicking catabolic gene alterations in
      degenerating chondrocytes.

PMID- 15955713
TI  - Quantile estimation to derive optimized test thresholds for random field
      statistics.
AB  - We present a numerical method to estimate the true threshold values in random
      fields needed to determine the significance of apparent signals observed in noisy
      images. To accomplish this, a quantile estimation algorithm is applied to derive
      the threshold with a predefined confidence interval from a large number of
      simulated random fields. Also, a computationally efficient method for generating
      a random field simulation is presented using resampling techniques. Applying
      these techniques, thresholds have been determined for a large variety of
      parameter settings (smoothness, voxel size, brain shape, type of statistics). By
      means of interpolation techniques, thresholds for additional arbitrary settings
      can be quickly derived without the need to run individual simulations. Compared
      to the parametric approach of Worsley et al. (1996) (Worsley, K.J., Marrett, S.,
      Neelin P., Vandal, A.C., Friston, K.J., Evans, A.C., 1996. A unified statistical
      approach for determining significant signals in images of cerebral activation.
      Hum. Brain Mapp. 4, 58-73) and Friston et al. (1991) (Friston, K.J., Frith, C.D.,
      Liddle, P.F., Frackowiak, R.S. 1991. Comparing functional (PET) images: the
      assessment of significant change. J. Cereb. Blood Flow Metab. 11(4), 690-699),
      and to the Bonferroni approach, these optimized thresholds lead to higher levels
      of significance (i.e., lower p values) with a specific amount of activation
      especially with fields of moderate smoothness (i.e., with a relative full width
      half maximum between 2 and 6). Alternatively, the threshold for a specified level
      of significance can be lowered. This improved statistical sensitivity is
      illustrated by the analysis of an actual event related functional magnetic
      resonance data set, and its limitations are tested by determining the false
      positive rate with experimental MR noise data. The grid of estimated threshold
      values as well as the interpolation algorithm to derive thresholds for arbitrary
      parameter settings are made available over the internet (http://neuro2.med.uni
      magdeburg.de/quantile_estimation).

PMID- 15955714
TI  - Self-perception of factors that precipitate or inhibit seizures in juvenile
      myoclonic epilepsy.
AB  - PURPOSE: To assess self-perception of factors that precipitate or inhibit
      seizures in patients with juvenile myoclonic epilepsy (JME). PATIENTS AND
      METHODS: Thirty-six males and 39 females with JME and mean age of 25.8+/-8.7
      years were analysed. All patients completed a standardized questionnaire to
      assess for the presence or absence of precipitant or inhibitory factors for their
      seizures in a face-to-face interview. These data were statistically analysed
      through logistic and linear regression models and Phi coefficient. RESULTS:
      Ninety-two percent of the patients identified at least one precipitating factor
      (PF). In order of frequency the following PFs were recorded: stress (83%), sleep
      deprivation (77%), specific thoughts/mental concentration (23%), performance of
      hand activities and complex finger movements (20%), flashing lights and playing
      games (15%), speaking out in public (11%) and alcohol intake (11%), reading (7%),
      calculating and writing (5%), playing musical instruments (4%), drawing (3%), and
      specific types of music (1%). Menstrual cycle was the third most important PF in
      the women (33%). Although PFs were easily recognized, 77% of the patients stated
      that they were unable to avoid the occurrence of the seizures. CONCLUSIONS:
      Structured questionnaire is useful in stimulating patients to self-report seizure
      precipitants. Patients with higher education and uncontrolled seizures identified
      them more easily. The presence of a significant number of uncommon PFs, such as
      mental and motor hand tasks, considered uncommon for other epileptic syndromes,
      suggests that the role of these factors may be under-recognized in JME.

PMID- 15955715
TI  - Muco-cutaneous candidiasis in two pigs with postweaning multisystemic wasting
      syndrome.
AB  - In two distinct commercial swine herds, poor weight gain and an increased number
      of animals showing wasting were observed among nursery and growing pigs. Cases of
      postweaning multisystemic wasting syndrome (PMWS) and infection with Haemophilus
      parasuis had been previously diagnosed in these herds. One growing wasted pig
      from each herd was necropsied and showed enlarged lymph nodes. Pseudomembranous
      material adhered to the dorsum of the tongue, soft and hard palate in case 1, and
      in case 2, fibrinous material was seen as whitish plaques on the oesophageal
      surface with hyperkeratosis of the non-glandular stomach. The main histological
      lesions in both cases were found in lymphoid tissues with a multifocal
      accentuated lymphohistiocytic infiltrate, areas of lymphoid depletion and
      intracytoplasmic inclusions in histiocytic cells in lymph nodes and Payer's
      patches. Focally, extensive ulceration was found in the stratified pavement
      epithelium of the tongue with necrosis and necrosuppurative infiltrate in case 1;
      in case 2, there was ulceration in the stomach with lymphohistiocytic infiltrate
      in the submucosa and ulceration in the mucosa of the oesophagus associated with
      yeast cells and pseudo-hyphae. Candida albicans was isolated from the oral cavity
      lesions. Immunohistochemistry of the lymph nodes was positive for porcine
      circovirus 2 (PCV2). The association between PMWS and mucocutaneous candidiasis
      reported here supports the potential immunosuppressive state of PMWS infected
      pigs.

PMID- 15955716
TI  - Addition of inhaled corticosteroid on combined bronchodilator therapy in patients
      with COPD.
AB  - PURPOSE: Bronchodilator therapy is the first step treatment in patients with
      COPD. The beneficial effects of corticosteroids either in health status or in
      airway inflammation in COPD have been previously studied. The aim of this study
      was to evaluate whether adding inhaled corticosteroids to combined bronchodilator
      therapy has additive clinical and anti-inflammatory effects in COPD patients.
      SUBJECTS AND METHODS: Thirty patients with COPD were included in the study. All
      patients were receiving inhaled anticholinergic and long-acting beta-2 agonist.
      Inhaled corticosteroid (budesonide 800 microg daily) was added to their current
      medications for 12 weeks. Before and after this treatment period, spirometric
      values and arterial blood gas parameters were determined, blood was drawn for
      measurement of serum inflammatory markers and sputum was induced. RESULTS: All
      patients were male, mean age was 67.7+/-8.7 years and duration of disease was
      9.7+/-4.3 years. The induced sputum total cell counts, eosinophil and neutrophil
      counts decreased with corticosteroid treatment. The induced sputum IL-8 and TNF
      alpha levels decreased significantly (IL-8; 835.9+/-217 versus 378.4+/-105 pg/ml,
      p=0.0001, TNF-alpha; 320.7+/-129 versus 201.3+/-52 pg/ml, p=0.003). Serum
      inflammatory markers and sputum LTB4 levels did not change with treatment.
      CONCLUSION: These results suggested that the addition of inhaled corticosteroids
      to combined bronchodilator therapy might have anti-inflammatory effects in
      patients with COPD.

PMID- 15955717
TI  - Adaptive branchial mechanisms in the sturgeon Acipenser naccarii during
      acclimation to saltwater.
AB  - Variations of Na(+)/K(+)-ATPase activity and fatty-acid composition in the gills
      of the sturgeon Acipenser naccarii subjected to progressive acclimation to full
      seawater (35 ppt) were determined in relation to the hypo-osmoregulatory capacity
      of this species in the hyperosmotic medium. Blood samples were taken and gills
      arches were removed at intermediate salinity levels between 0 and 35 ppt and
      after 20 days at constant salinity (35 ppt). Plasma osmolality and Na(+)/K(+)
      ATPase activity increased significantly with growing environmental salinity.
      Total saturated fatty acids (SFAs) decreased, while total polyunsaturated fatty
      acids (PUFAs) increased significantly with increasing salinity due mainly to
      changes in n-3 PUFAs (20:5n-3 and 22:6n-3). The n-3/n-6 ratio increased
      significantly during the acclimation process. The results show a direct
      relationship between salinity, increased gill Na(+)/K(+)-ATPase activity and
      ultrastructural changes of the gill chloride cells. Changes in the fatty-acid
      composition in gills of A. naccarii during progressive acclimation to full
      seawater suggest that variations of gill fatty acids may also have a role in
      osmoregulatory mechanisms.

PMID- 15955718
TI  - An AOTF-based dual-modality hyperspectral imaging system (DMHSI) capable of
      simultaneous fluorescence and reflectance imaging.
AB  - An acousto-optic tunable filter (AOTF)-based system for dual-modality
      hyperspectral imaging (DMHSI) has been developed for use in characterization of
      normal and malignant mouse tissue. The system consists of a laser, endoscope,
      AOTF, and two cameras coupled with optics and electronics. Initial results show
      that the system can delineate normal and malignant mouse tissues real-time. The
      analysis shows that malignant tissues consistently exhibit less fluorescent
      intensity in the wavelength band from 440 to 540 nm with a peak intensity of
      around 490 nm. The analysis also shows key spectroscopic differences between
      normal and malignant tissues. Further, these results are compared to real-time
      spectroscopic data and show good correlation.

PMID- 15955719
TI  - Gene therapy in the cornea.
AB  - Technological advances in the field of gene therapy has prompted more than three
      hundred phase I and phase II gene-based clinical trials for the treatment of
      cancer, AIDS, macular degeneration, cardiovascular, and other monogenic diseases.
      Besides treating diseases, gene transfer technology has been utilized for the
      development of preventive and therapeutic vaccines for malaria, tuberculosis,
      hepatitis A, B and C viruses, AIDS, and influenza. The potential therapeutic
      applications of gene transfer technology are enormous. The cornea is an excellent
      candidate for gene therapy because of its accessibility and immune-privileged
      nature. In the last two decades, various viral vectors, such as adeno, adeno
      associated, retro, lenti, and herpes simplex, as well as non-viral methods, were
      examined for introducing DNA into corneal cells in vitro, in vivo and ex vivo.
      Most of these studies used fluorescent or non-fluorescent marker genes to track
      the level and duration of transgene expression in corneal cells. However, limited
      studies were directed to evaluate prospects of gene-based interventions for
      corneal diseases or disorders such as allograft rejection, laser-induced post
      operative haze, herpes simplex keratitis, and wound healing in animal models. We
      will review the successes and obstacles impeding gene therapy approaches used for
      delivering genes into the cornea.

PMID- 15955720
TI  - Does living in rural areas make a difference for health in Quebec?
AB  - This study offers an overview of the health status of rural populations and its
      major determinants in Quebec. A wide range of indicators are examined along a
      spatial grid that allows rural-urban as well as intrarural comparisons.
      Differences between urban and rural populations mainly concern specific health
      problems and determinants, while notable variations on these are noted within
      rural areas. Some avenues for further research and public health policies in
      Quebec are presented.

PMID- 15955721
TI  - Ubiquitin-proteasome-dependent proteolytic activity remains elevated after
      zymosan-induced sepsis in rats while muscle mass recovers.
AB  - We studied the role of the ubiquitin-proteasome system in rat skeletal muscle
      during sepsis and subsequent recovery. Sepsis was induced with intraperitoneal
      zymosan injections. This model allows one to study a sustained and reversible
      catabolic phase and mimics the events that prevail in septic and subsequently
      recovering patients. In addition, the role of the ubiquitin-proteasome system
      during muscle recovery is poorly documented. There was a trend for increased
      ubiquitin-conjugate formation in the muscle wasting phase, which was abolished
      during the recovery phase. The trypsin- and chymotrypsin-like peptidase
      activities of the 20S proteasome peaked at day 6 following zymosan injection
      (i.e. when both muscle mass and muscle fiber cross-sectional area were reduced
      the most), but remained elevated when muscle mass and muscle fiber cross
      sectional area were recovering (11 days). This clearly suggests a role for the
      ubiquitin-proteasome pathway in the muscle remodeling and/or recovery process.
      Protein levels of 19S complex and 20S proteasome subunits did not increase
      throughout the study, pointing to alternative mechanisms regulating proteasome
      activities. Overall these data support a role for ubiquitin-proteasome dependent
      proteolysis in the zymosan septic model, in both the catabolic and muscle
      recovery phases.

PMID- 15955722
TI  - A unified model for perceptual learning.
AB  - Perceptual learning in adult humans and animals refers to improvements in sensory
      abilities after training. These improvements had been thought to occur only when
      attention is focused on the stimuli to be learned (task-relevant learning) but
      recent studies demonstrate performance improvements outside the focus of
      attention (task-irrelevant learning). Here, we propose a unified model that
      explains both task-relevant and task-irrelevant learning. The model suggests that
      long-term sensitivity enhancements to task-relevant or irrelevant stimuli occur
      as a result of timely interactions between diffused signals triggered by task
      performance and signals produced by stimulus presentation. The proposed mechanism
      uses multiple attentional and reinforcement systems that rely on different
      underlying neuromodulators. Our model provides insights into how neural
      modulators, attentional and reinforcement learning systems are related.

PMID- 15955723
TI  - Nod factor signaling genes and their function in the early stages of Rhizobium
      infection.
AB  - A lipochitosaccharide-based signal molecule that is secreted by Rhizobium, named
      Nod factor (NF), induces root nodule formation in legumes. This molecule is also
      essential for the establishment of bacterial infection. Genetic analyses in the
      legume species Lotus japonicus and Medicago truncatula have led to the
      identification of many components of the NF signaling cascade. At least three of
      these genes do not function exclusively in the Rhizobium symbiosis but are also
      essential for the formation of mycorrhiza, an endosymbiosis found in many higher
      plant species. Recent studies have advanced our understanding of the functions of
      NF signaling genes in the Rhizobium infection process and the extent to which
      these genes are unique to legumes.

PMID- 15955724
TI  - EPR investigations on radiation induced chemical transformations in Pd(ClO4)2/i
      PrOH/HClO4 system from 77 to 300 K.
AB  - The EPR studies have been carried out on gamma irradiated samples of Pd(ClO4)2 in
      9 M/4M HClO4 in the presence and absence of isopropanol [i-PrOH (5%, v/v)], in
      the temperature range of 77-300 K. The EPR studies revealed the formation of Pd+
      complex, Pd3+ complex and several radicals such as H., OH., ClO3., ClO4. and O3-
      on radiolysis of these systems. Reduction of Pd2+ to Pd clusters could not be
      observed in the absence of i-PrOH and warming of the irradiated sample finally
      resulted in recovery of Pd2+ complex. However, in the presence of 5% i-PrOH,
      strongly oxidizing radicals like OH., ClO3. and ClO4. are suppressed and
      (CH3)2C.OH radical was produced along with reducing species like H.. EPR spectra
      in these strongly reducing conditions showed formation of Pd+ complex, which on
      heating above 230 K, disproportionated into Pd0 and Pd2+ complex and finally lead
      to formation of Pd metal aggregates. Simultaneously, pulse radiolysis technique
      has been employed as an alternative method to verify the EPR observations.

PMID- 15955725
TI  - On the dynamics of the TPPS4 aggregation in aqueous solutions: successive
      formation of H and J aggregates.
AB  - The dynamics of aggregation of meso-tetrakis (p-sulfonatofenyl) porphyrin (TPPS4)
      in function of its concentration, pH and ionic strength was studied by optical
      absorption, fluorescence and resonance light scattering (RLS) techniques. In the
      region of pH, where TPPS4 exists in biprotonated form, the addition of NaCl
      induces the TPPS4 aggregation due to the formation of the "cloud" of counter ions
      around the TPPS4 molecule thus reducing electrostatic repulsion between the
      porphyrin molecules. The formation of this "cloud" shifts the pKa value to acid
      region (from 5.0 in the absence of salt to 4.5 at [NaCl] = 0.4 M), reduces the
      TPPS4 absorption in all spectral range and quantum yield and lifetime of
      fluorescence (from 0.27 to 0.17 and from 4.00+/-0.04 to 3.00+/-0.03 ns in the
      absence of salt and in the presence of NaCl, respectively). The aggregation
      process involves two successive stages: initially H aggregates are formed, which
      in time are transformed in J ones. The existence of these two stages was
      confirmed by the fluorescence and RLS data. The kinetics of the formation of J
      aggregates is characterized by the induction time t1 and the average growth time
      t2, which depend on both TPPS4 and salt concentrations. The induction period t1
      appears as a result of initial formation of H aggregates and their successive
      transformation in J ones. At very high TPPS4 concentrations, the J aggregates are
      united in more complex structures such as hollow cylinders or helixes.

PMID- 15955726
TI  - Spectroscopic identification of S-Au interaction in cysteine capped gold
      nanoparticles.
AB  - This study deals with the synthesis of cysteine capped gold nanoparticles with an
      average size of 12 nm by borohydride reduction and spectroscopic identification
      of SAu interaction. We have studied the interaction of thiol with gold
      nanoparticles in aqueous medium by employing UV-vis, Raman, NMR, and FT-IR
      spectroscopy. The shifting of gold plasmon resonance in the UV-vis spectra shows
      the stabilization of gold nanoparticles by cysteine. The disappearance of S-H
      stretching in both the IR and Raman spectra and the shifting of the NMR signals
      of the protons in close proximity to the metal center supported the existence of
      the S-Au interaction in cysteine capped gold nanoparticles. The TEM images shows
      cysteine capped gold nanoparticles as distinct and spherical entities as compared
      to free colloidal gold nanoparticles.

PMID- 15955727
TI  - Synthesis, spectral characterization and biological studies of some organotin(IV)
      complexes of L-proline, trans-hydroxy-L-proline and L-glutamine.
AB  - New organotin(IV) complexes of the general formula R3Sn(L) (where R=Me, n-Bu and
      HL=L-proline; R=Me, Ph and HL=trans-hydroxy-L-proline and L-glutamine) and
      R2Sn(L)2 (where R=n-Bu, Ph and HL=L-proline; R=Ph, HL=trans-hydroxy-L-proline)
      have been synthesized by the reaction of RnSnCl(4-n) (where n=2 or 3) with sodium
      salt of the amino acid (HL). n-Bu2Sn(Pro)2 was synthesized by the reaction of n
      Bu2SnO with L-proline under azeotropic removal of water. The bonding and
      coordination behavior in these complexes have been discussed on the basis of IR
      and 119Sn Mossbauer spectroscopic studies in the solid-state. Their coordination
      behavior in solution has been discussed with the help of multinuclear (1H, 13C
      and 119Sn) NMR spectral studies. The 119Sn Mossbauer and IR studies indicate that
      L-proline and trans-hydroxy-L-proline show similar coordination behavior towards
      organotin(IV) compounds. Pentacoordinate trigonal-bipyramidal and hexacoordinate
      octahedral structures, respectively, have been proposed for the tri- and
      diorganotin(IV) complexes of L-proline and trans-hydroxy-L-proline, in which the
      carboxylate group acts as bidentate group. L-glutamine shows different
      coordination behavior towards organotin(IV) compounds, it acts as monoanionic
      bidentate ligand coordinating through carboxylate and amino group. The
      triorganotin(IV) complexes of L-glutamine have been proposed to have trigonal
      bipyramidal environment around tin. The newly synthesized complexes have been
      tested for their antiinflammatory and cardiovascular activities. Their LD50
      values are >1000 mg kg-1.

PMID- 15955728
TI  - Synthesis, characterization and biological activity of some transition metals
      with Schiff base derived from 2-thiophene carboxaldehyde and aminobenzoic acid.
AB  - Metal complexes of Schiff base derived from 2-thiophene carboxaldehyde and 2
      aminobenzoic acid (HL) are reported and characterized based on elemental
      analyses, IR, 1H NMR, solid reflectance, magnetic moment, molar conductance and
      thermal analysis (TGA). The ligand dissociation as well as the metal-ligand
      stability constants were calculated pH metrically at 25 degrees C and ionic
      strength mu=0.1 (1M NaCl). The complexes are found to have the formulae
      [M(HL)2](X)n.yH2O (where M=Fe(III) (X=Cl, n=3, y=3), Co(II) (X=Cl, n=2, y=1.5),
      Ni(II) (X=Cl, n=2, y=1) and UO2(II) (X=NO3, n=2, y=0)) and [M(L)2] (where
      M=Cu(II) (X=Cl) and Zn(II) (X=AcO)). The molar conductance data reveal that
      Fe(III) and Co(II), Ni(II) and UO2(II) chelates are ionic in nature and are of
      the type 3:1 and 2:1 electrolytes, respectively, while Cu(II) and Zn(II)
      complexes are non-electrolytes. IR spectra show that HL is coordinated to the
      metal ions in a terdentate manner with ONS donor sites of the carboxylate O,
      azomethine N and thiophene S. From the magnetic and solid reflectance spectra, it
      is found that the geometrical structure of these complexes are octahedral. The
      thermal behaviour of these chelates shows that the hydrated complexes losses
      water molecules of hydration in the first step followed immediately by
      decomposition of the anions and ligand molecules in the subsequent steps. The
      activation thermodynamic parameters, such as, E*, DeltaH*, DeltaS* and DeltaG*
      are calculated from the DrTG curves using Coats-Redfern method. The synthesized
      ligands, in comparison to their metal complexes also were screened for their
      antibacterial activity against bacterial species, Escherichia coli, Pseudomonas
      aeruginosa, Staphylococcus pyogones and Fungi (Candida). The activity data show
      that the metal complexes to be more potent/antibacterial than the parent Schiff
      base ligand against one or more bacterial species.

PMID- 15955729
TI  - Dielectric relaxation spectroscopy of heteronuclear cobalt(II)-copper(II) complex
      of 1-phenyl-3-methyl-5-pyrazolone.
AB  - A bright green CoCu(PMP)(OH)2(H2O)2 complex was synthesized. Its structure was
      elucidated and characterized by different spectroscopic techniques. Both cobalt
      and copper atoms attain tetrahedral geometry. The complex was investigated by the
      dielectric relaxation spectroscopy. The dielectric parameters are discussed in
      terms of temperature and frequency changes. The conductivity of the complex
      decreased as the temperature increased in the temperature range 30-100 degrees C,
      while above this temperature range stepwise increase in the conductivity was
      observed.

PMID- 15955730
TI  - Structural and thermal characterization of cerium, thorium and uranyl complexes
      of sulfasalazine.
AB  - Cerium(IV), Thorium(IV) and Uranyl(II) complexes with the ammonium salt of
      sulfasalazine drug (H2SSZ, HL-) have been studied. The structures of the
      complexes were elucidated using elemental analysis, IR and mass spectroscopy and
      thermal analysis. The complexes were isolated in 1:1 and 1:2 (M:L) ratios. The
      solid monocomplexes (1:1) (M:H(2)SSZ) were isolated in the general formulae
      [UO2(L)(H2O)2].2H2O and [M(L)(X)z(H2O)n].yH2O (M=Ce(IV) and Th(IV) (X=NO3, z=2,
      n=2, y=0-3)). The biscomplexes (1:2) (M:H2SSZ) solid chelates found to have the
      general formulae [UO2(HL)2].2H2O and [M(L)2(H2O)2] (M=Ce(IV) and Th(IV)). The
      thermal decomposition of the complexes should be discussed in relation to
      structure, and the thermodynamic parameters of the decomposition stages were
      evaluated applying Coats-Redfern and Horwitz-Mitzger methods.

PMID- 15955731
TI  - Spectrophotometric determination of the dissociation constants of crown ethers
      with grafted acridone unit in methanol based on Benesi-Hildebrand evaluation.
AB  - As potential chromo- and fluorophores for optical sensors a number of acridone
      grafted crown ethers containing NO2 group(s) and/or Br or Cl atom(s) in the
      aromatic rings (compounds) were studied by spectrophotometric method. In the
      first step of this work the acid-base and complexing properties of these
      compounds as well as those of the acridone, thioacridone and 4,5-dinitroacridone
      were investigated. Compounds proved to be very week acids and therefore the
      conventional spectrophotometric method based on the measurement of the ratio of
      the protonated/deprotonated forms of the compounds was not applicable for the
      determination of the dissociation constants (pKa values). Thus, a new
      spectrophotometric approach was elaborated for the pKa determination of these
      compounds, which is based on spectrophotometric titration in methanol with strong
      base and the titration results were evaluated by the Benesi-Hildebrand method.
      (In the studies with TEAOH, TMAOH and LiOMe, the complex formation between the
      ionophores and the cations of the bases could be excluded.) As it was expected,
      the experimentally determined pKa values depended on the nature of the
      substituents of the acridone moiety and pKa values ranged between 12.6 and 14.9.
      The lower pKa value of thioacridone compared to the acridone can be explained by
      the larger size of the sulfur atom. The outstandingly larger pKa value for 4,5
      dinitroacridone can be attributed to the formation of intramolecular hydrogen
      bonds between the ortho-position nitro group and the NH proton. As a trend, the
      strong electron withdrawing nitro substituents decreased considerably the pKa
      values of compounds and compared to that of the halogen (Cl and Br) atoms (for
      example compounds and) of weaker withdrawing effect.

PMID- 15955732
TI  - Implementation of automated signal generation in pharmacovigilance using a
      knowledge-based approach.
AB  - Automated signal generation is a growing field in pharmacovigilance that relies
      on data mining of huge spontaneous reporting systems for detecting unknown
      adverse drug reactions (ADR). Previous implementations of quantitative techniques
      did not take into account issues related to the medical dictionary for regulatory
      activities (MedDRA) terminology used for coding ADRs. MedDRA is a first
      generation terminology lacking formal definitions; grouping of similar medical
      conditions is not accurate due to taxonomic limitations. Our objective was to
      build a data-mining tool that improves signal detection algorithms by performing
      terminological reasoning on MedDRA codes described with the DAML+OIL description
      logic. We propose the PharmaMiner tool that implements quantitative techniques
      based on underlying statistical and bayesian models. It is a JAVA application
      displaying results in tabular format and performing terminological reasoning with
      the Racer inference engine. The mean frequency of drug-adverse effect
      associations in the French database was 2.66. Subsumption reasoning based on
      MedDRA taxonomical hierarchy produced a mean number of occurrence of 2.92 versus
      3.63 (p < 0.001) obtained with a combined technique using subsumption and
      approximate matching reasoning based on the ontological structure. Semantic
      integration of terminological systems with data mining methods is a promising
      technique for improving machine learning in medical databases.

PMID- 15955733
TI  - Aspirin and steroids: new mechanistic findings and avenues for drug discovery.
AB  - The inflammatory response is a life-saving protective process mounted by the body
      to overcome pathogen infection and injury; however, in chronic inflammatory
      pathologies, this response can become deregulated. Aspirin and glucocorticoids
      are two examples of drugs developed over the years to rectify deregulated
      inflammatory reactions. Interestingly, both these prototypes of anti-inflammatory
      therapeutics have been 'borrowed' from Mother Nature, identified from the plant
      and animal world, respectively. In the past century, systematic organic chemistry
      has been the major approach for producing new drugs, and vast quantities of
      aspirin and prednisolone have been synthesized, packaged and sold. However, the
      fascination provoked by these often life-saving drugs has not subsided, and
      recent work into the endogenous control of the host inflammatory response has
      revitalized these compounds. Thus, epi-lipoxins, produced after aspirin
      acetylation of inducible cyclooxygenase-2, and glucocorticoid-regulated annexin 1
      appear to be important endogenous mediators of their respective anti-inflammatory
      effects. In addition, aspirin-triggered epi-lipoxins and glucocorticoid-regulated
      annexin 1 might act on the same G-protein-coupled receptor, thus rendering this
      shared receptor a more likely and worthwhile target for fruitful drug discovery.

PMID- 15955734
TI  - Recent progress in targeting the Raf/MEK/ERK pathway with inhibitors in cancer
      drug discovery.
AB  - Since the discovery that activating mutations of the Ras GTPase were associated
      with 30% or more of human cancers, the RAF/MEK/ERK pathway has been the focus of
      intense drug discovery effort. Within the new class of molecularly targeted anti
      cancer agents progressing through the late stages of clinical development, BAY 43
      9006 and PD0325901 have shown considerable promise.

PMID- 15955735
TI  - Anti-adhesion therapies.
AB  - Cell adhesion molecules are key mediators of inflammatory processes and are
      attractive targets for discovery of novel therapeutics. There have been
      significant positive advances in both basic research and clinical development in
      this area. Basic research has yielded detailed insight into the structural basis
      of cell adhesion molecule function, especially the interaction of integrins with
      their ligands. Co-crystals of several integrin-ligand complexes have been
      published, including alpha v beta3 with ligand fragments, alpha IIb beta3 with
      multiple therapeutic ligands and alpha L beta2 (leukocyte function-associated
      antigen-1 [LFA-1]) with its cell-based ligand intercellular adhesion molecule-1.
      This has stimulated development of models of integrin function and also the mode
      of action of small-molecule inhibitors. The most exciting recent advances in the
      field of clinical development have come with the successful approval of two new
      anti-adhesion therapeutics: efalizumab (Raptiva) targeting LFA-1 for the
      treatment of chronic plaque psoriasis, and natalizumab (Tysabri/Antegren)
      targeting very late antigen-4 for the treatment of relapsing-remitting multiple
      sclerosis. However, the latter therapeutic ran into a surprising safety issue
      earlier this year and was withdrawn from the market, casting a shadow over what
      had seemed a promising new drug.

PMID- 15955736
TI  - Targeting the DNA repair defect of BRCA tumours.
AB  - Carriers of heterozygous mutations in BRCA1 or BRCA2 are strongly predisposed to
      breast and ovarian cancers. Cancers arising in these individuals have
      consistently lost the wild-type allele during tumour progression, and are
      therefore deficient in BRCA1 or BRCA2 function. Both BRCA1 and BRCA2 proteins
      have been implicated in the repair of double-strand DNA breaks by homologous
      recombination. This functional role in DNA repair could be exploited in the
      treatment of BRCA-deficient cancers by targeting the tumours with drugs that
      create DNA damage highly reliant on BRCA1 or BRCA2 for repair.

PMID- 15955737
TI  - Identification of G-protein-coupled receptors involved in inflammatory disease by
      genetic association studies.
AB  - G-protein-coupled receptors are not only highly tractable drug targets but also
      attractive candidates for genetic association studies because they are more
      polymorphic than most other classes of gene and these polymorphisms frequently
      lead to functional changes in the levels of expression or biological activity
      that can predispose to common diseases. A large-scale study to identify
      functional variants in G-protein-coupled receptors associated with inflammatory
      diseases has highlighted a spectrum of novel biological insights that range from
      identifying the involvement of orphan receptors in certain diseases through to
      highlighting new therapeutic indications for existing drugs.

PMID- 15955738
TI  - Tumour invasion and metastasis: challenges facing drug discovery.
AB  - Initial attempts at directly targeting metastatic spread using inhibitors of
      matrix metalloproteases failed to deliver the promise of anti-invasive therapy. A
      new generation of targeted agents with the potential to act as anti-invasives has
      recently entered the clinic but there is, as yet, no clear route to demonstrate
      an effect upon tumour metastasis. Because advances with monoclonal antibodies are
      likely to increase the number of potential anti-invasive agents, more clinically
      predictive drug discovery cascades are required to reduce the perceived risks
      associated with their generation. Once they reach the clinic, new approaches will
      be essential to help early indicators of clinical response meet ethical standards
      and avoid unnecessary clinical failures.

PMID- 15955739
TI  - mTOR--beyond transplantation.
AB  - mTOR kinase plays a central role in the activation of many cell types, and
      blocking mTOR function with rapamycin results in arrest of the cell cycle at the
      G1 phase. Recently, several additional molecules have been identified in the mTOR
      pathway, providing further opportunities to interfere with cell activation and
      develop novel therapeutic agents. Under certain conditions and in specific cell
      types, activation can occur independently of mTOR and in the presence of
      rapamycin. Selective inhibition of cell activation in the appropriate setting
      might prove to be beneficial for several autoimmune or inflammatory diseases.

PMID- 15955740
TI  - Siglecs in innate immunity.
AB  - Siglecs are sialic acid-binding Ig-like lectins expressed in a highly specific
      manner, and which are implicated in signaling and adhesive functions. The CD33
      related siglecs represent a distinct subgroup that is undergoing rapid evolution
      within the innate immune system, with the potential to trigger apoptosis and
      provide inhibitory signals. CD22 is a well-characterised B cell restricted siglec
      that has been shown to mediate both sialic acid-dependent and -independent
      signaling functions in B cell regulation. As endocytic receptors, siglecs provide
      portals of entry for certain viral and bacterial pathogens, as well as
      therapeutic opportunities for targeting innate immune cells in disease.

PMID- 15955741
TI  - Rehabilitation of cancer through oncogene inactivation.
AB  - The inactivation of the MYC oncogene alone can reverse tumorigenesis. Upon MYC
      inactivation, tumors stereotypically reverse, undergoing proliferative arrest,
      cellular differentiation and/or apoptosis. The precise consequences of MYC
      inactivation appear to depend upon both genetic and epigenetic parameters. In
      some types of cancer following MYC inactivation, tumor cells become well
      differentiated and biologically and histologically normal, inducing sustained
      tumor regression. However, in some cases, these normal-appearing cells are
      actually dormant tumor cells and upon MYC reactivation they rapidly recover their
      tumorigenic properties. Future therapies to treat cancer will need to address the
      possibility that tumor cells can camouflage a normal phenotype following
      treatment, resting in a dormant, latently cancerous state.

PMID- 15955742
TI  - Response to Rigato et al.: bilirubin and non-hepatic disease--a jaundiced view.

PMID- 15955743
TI  - NOD2 mutation and mice: no Crohn's disease but many lessons to learn.
AB  - Many patients with ileal Crohn's disease, a chronic intestinal inflammation,
      carry mutations in the gene encoding NOD2 (CARD15), but the mechanistic details
      of how this mutation leads to disease are not fully understood. NOD2 is expressed
      in antigen-presenting cells and Paneth cells, which are secretory epithelial
      cells of the small intestine. Two complementary studies using genetically
      engineered murine models help to explain the association of NOD2 malfunction and
      mucosal disease. One study observes a dysregulation of proinflammatory responses,
      suggesting that the most common NOD2 mutation in humans results in a gain of
      function. The other study determined that NOD2-null mutations impair the Paneth
      cell antimicrobial response, which is consistent with recent findings in humans.
      Together, these studies fuel optimism that new therapeutic directions might
      emerge to better treat this severe mucosal disease.

PMID- 15955744
TI  - Uterus-conserving surgery for invasive cervical cancer.
AB  - Standard treatment for cervical cancer is either radical hysterectomy or
      radiotherapy to the pelvis. Either will inevitably compromise fertility,
      rendering future childbearing impossible. Precise staging and magnetic resonance
      imaging can indicate the site and location of the tumour. Radical wide local
      excision of early-stage small tumours can allow conservation of the uterine
      corpus and the potential for fertility preservation. An isthmic vaginal
      anastomosis restores continuity of the vaginal canal after insertion of an
      isthmic cerclage. This will keep the isthmus competent but still allow
      menstruation. Pelvic lymphadenectomy is performed laparoscopically. This new
      approach combines current developing minimal access techniques with laparoscopic
      pelvic sidewall dissection and lymphadenectomy. The bottom or inferior part of a
      traditional radical vaginal hysterectomy is performed simultaneously. Over 400
      cases have been reported with 100 live births. Premature rupture of the membranes
      is a risk. Delivery is by classical Caesarean section. Fertility rates are good
      and recurrence rates are low at 4%. This technique appears to be safe in well
      selected cases and when performed in centres with suitable experience of radical
      vaginal surgery and laparoscopic techniques. Obstetric management in high-risk
      feto-maternal units is necessary in view of the risk of prematurity.

PMID- 15955745
TI  - Vascular endothelin in hypertension.
AB  - Endothelins are powerful vasoconstrictor peptides that also play numerous other
      functions in many different organs. Endothelin-1 (ET-1) is the most abundant and
      important of this family of peptides in blood vessels. Production of ET-1 is
      increased in the endothelium and the kidney in salt-dependent models of
      hypertension (e.g.: DOCA-salt rats and Dahl salt-sensitive rats, in salt-loaded
      SHR-SP, in angiotensin II-infused and in diabetic rats). ET-1 elicits an
      inflammatory response by increasing oxidant stress in the vascular wall, which
      induces vascular remodeling and endothelial dysfunction found in the hypertensive
      models that exhibit an endothelin-mediated component. Endothelin receptor
      antagonism reduces blood pressure and vascular hypertrophic remodeling present in
      these hypertensive models. Patients with stage 2 hypertension have enhanced
      vascular expression of ET-1. Endothelin receptor antagonists lower blood pressure
      in hypertensive patients. They could become therapeutic agents for prevention of
      target organ damage in hypertension and in type 2 diabetes, chronic renal failure
      and congestive heart failure. Side effects of endothelin receptor blockers have
      prevented up to the present their development for these indications. New
      endothelin antagonists devoid of these side effects, or alternatively inhibitors
      of the endothelin converting enzymes that generate ET-1 may in the future become
      available to block the endothelin system. However, to date endothelin antagonists
      have been approved only for the treatment of primary pulmonary hypertension, a
      rapidly fatal condition in which the endothelin system plays an important role
      and endothelin antagonists exert favorable effects.

PMID- 15955746
TI  - Neurotransmission and neuromodulation in the chemosensory carotid body.
AB  - The mammalian carotid body is a small chemosensory organ that helps maintain the
      chemical composition of arterial blood via reflex control of ventilation. Thus,
      in response to decreased PO2 (hypoxia), increased PCO2 (hypercapnia), or
      decreased pH (acidity), chemoreceptor glomus or type I cells become stimulated
      and release neuroactive agents that excite apposed sensory terminals of the
      carotid sinus nerve. The resulting increase in afferent discharge ultimately
      leads to corrective changes in ventilation so as to maintain blood gas and pH
      homeostasis. Recent evidence that the organ can also sense low glucose further
      emphasizes its role as a polymodal sensor of blood-borne stimuli. The
      chemoreceptors occur in organized cell clusters that receive sensory innervation
      from petrosal afferents and are intimately associated with the blood supply.
      Additionally, synaptic specializations between neighboring receptor cells allow
      for autocrine and paracrine regulation of the sensory output. Though not without
      controversy, significant progress has been made in elucidating the various
      chemotransductive pathways, as well as the neurotransmitter and neuromodulatory
      mechanisms that translate the receptor potential into an afferent sensory
      discharge. Progress in the latter has been hampered by the presence of a wide
      variety of endogenous ligands, and an even broader spectrum of receptor subtypes,
      that apparently help shape the chemoreceptor output and afferent discharge. This
      review will highlight recent advances in understanding the role of these
      neuroactive ligands in carotid body function.

PMID- 15955747
TI  - Heterogenous changes in neuropeptide Y, norepinephrine and epinephrine
      concentrations in the hearts of diabetic rats.
AB  - The changes in concentrations of neuropeptide Y (NPY), norepinephrine and
      epinephrine were investigated in the rat hearts 1, 2, 4, 6, 9 and 12 months after
      administration of streptozotocin (STZ; 65 mg/kg i.v.). About 30% of diabetic
      animals displayed symptoms of partial spontaneous recovery, i.e. decreasing blood
      glucose levels and increasing insulin concentrations in the plasma and pancreas.
      NPY concentrations in the atria of diabetic rats did not differ from those in age
      matched control rats 1, 2, 4, 6 months in the right atria and even 9 months after
      STZ in the left atria. However, uncompensated diabetes led to a significant
      decrease in NPY levels 9 and 12 months after STZ administration in the right and
      left atria, respectively. In the ventricles, NPY concentrations were
      significantly decreased 6 months after the onset of diabetes. Interestingly,
      partial spontaneous recovery of diabetes was associated with increased NPY levels
      in the atria. Myocardial norepinephrine concentrations increased 1 month after
      STZ and then declined reaching approximately 60% of the respective control values
      12 months after the onset of the disease. Partial spontaneous recovery of
      diabetes had no effect on norepinephrine concentrations. Myocardial epinephrine
      concentrations did not differ from those found in controls till month 9 of the
      disease and they became significantly lower at month 12. Partial recovery of
      diabetes resulted in epinephrine concentrations not differing from the control
      values at month 12 of diabetes. Regarding to preferential localization of
      norepinephrine in the sympathetic postganglionic fibers and that of NPY also in
      intrinsic ganglion neurons, intrinsic neuronal circuits seem to be less
      susceptible to STZ-induced damage than extrinsic nerves and they might be able to
      recover after amelioration of diabetes.

PMID- 15955748
TI  - Distribution and mixing of a liquid bolus in pleural space.
AB  - Distribution and mixing time of boluses with labeled albumin in pleural space of
      anesthetized, supine rabbits were determined by sampling pleural liquid at
      different times in various intercostal spaces (ics), and in cranial and caudal
      mediastinum. During sampling, lung and chest wall were kept apposed by lung
      inflation. This was not necessary in costo-phrenic sinus. Here, 10 min after
      injection, lung inflation increased concentration of labeled albumin by 50%. Lung
      inflation probably displaces some pleural liquid cranio-caudally, increasing
      labeled albumin concentration caudally to injection point (6th ics), and
      decreasing it cranially. Boluses of 0.1-1 ml did not preferentially reach
      mediastinal regions, as maintained by others. Time for an approximate mixing was
      approximately 1 h for 0.1 ml, and approximately 30 min for 1 ml. This relatively
      long mixing time does not substantially affect determination of contribution of
      lymphatic drainage through stomata to overall removal of labeled albumin from 0.3
      ml hydrothoraces lasting 3 h [Bodega, F., Agostoni, E., 2004. Contribution of
      lymphatic drainage through stomata to albumin removal from pleural space. Respir.
      Physiol. Neurobiol. 142, 251-263].

PMID- 15955749
TI  - Characterization of a thermostable alkaline phosphatase from a novel species
      Thermus yunnanensis sp. nov. and investigation of its cobalt activation at high
      temperature.
AB  - A thermostable alkaline phosphatase with high specific activity and thermal
      resistance was purified from a novel species of Thermus sp. named as Thermus
      yunnanensis sp. nov. The enzyme contains a single peptide with a molecular mass
      of about 52 kDa on SDS-PAGE analysis and appears to be a homodimer in solution
      with the molecular mass of 104 kDa. The optimal pH and temperature for its
      activities are pH 8.0-10.0 and 70-80 degrees C, respectively. The catalytic
      activities of the enzyme are metal ion dependent, and Mg2+, Zn2+ and Co2+ are the
      main activators. Among these, Co2+ is the most active stimulator and has unique
      activation effect at high temperature. Metal binding analysis showed the binding
      of Mg2+ at the metal binding site was easy to loss in the thermoinactivation, and
      Co2+ was apt to bind at that site and kept the favorable configuration of
      catalysis, which would result high activation in the incubation with Co2+ at high
      temperature. According to this study, a model was proposed for the explanation of
      the activation and the results of actual experiments demonstrated the validity of
      the model.

PMID- 15955750
TI  - Conformational detours during folding of a collapsed state.
AB  - The protein S6 is a useful model to probe the role of partially folded states in
      the folding process. In the absence of salt, S6 folds from the denatured state D
      to the native state N without detectable intermediates. High concentrations of
      sodium sulfate induce the accumulation of a collapsed state C, which is off the
      direct folding route. However, the mutation VA85 enables S6 to fold from C
      directly to N through the transition state TS(C). According to the denaturant
      dependence of this reaction, TS(C) and C are equally compact, but the data are
      difficult to deconvolute. Therefore, I have measured the heat capacities
      (DeltaC(p)) for the D-->C and C-->TS(C) transitions. The DeltaC(p)-values suggest
      that C needs to increase its surface area in order to fold directly to N. This
      underlines that it is a misfolded state that can only fold by at least partial
      unfolding. In contrast to the C-state formed by S6 wildtype, the VA85 C-state is
      just as compact as the native state, and this may be a prerequisite for direct
      folding. Individual "gatekeeper" residues may thus play a disproportionately
      large role in guiding proteins through different folding pathways.

PMID- 15955751
TI  - Older hospitalised patients at risk of malnutrition: correlation with quality of
      life, aid from the social welfare system and length of stay?
AB  - BACKGROUND: malnutrition is regarded as a major risk factor for complications and
      delayed recovery in hospitalised elderly patients. OBJECTIVE: to examine the
      prevalence of malnutrition in hospitalised elderly patients and evaluate simple
      clinical screening criteria. To investigate whether malnutrition was related to
      lack of care from the health care or social welfare system, quality of life and
      hospital length of stay (LOS). SETTING: non-acute geriatric hospital. SUBJECTS:
      294 elderly patients admitted for rehabilitation after acute hospital care; 244
      patients were available for assessment. METHODS: questionnaire interview about
      nutrition, social network and quality of life. Anthropometric and biochemical
      measurements, assessment of physical and cognitive function, recording of LOS,
      discharge destination and diagnosis. RESULTS: 126 patients (51.6%) were at risk
      of malnutrition using the criteria of body mass index<22 kg/m2 and/or weight
      loss>or=5%/6 months. Poor quality of life in women (P<0.04) and loss of the
      health of a spouse (P<0.02) correlated with weight loss. No differences were
      found in patients at risk regarding LOS, discharge destination, or aid from the
      social welfare system. CONCLUSIONS: this study confirms a high prevalence of
      malnutrition risk in hospitalised elderly patients. The health care and social
      welfare system appeared to be unaware of the problem. Poor quality of life in
      females and loss of the health of a spouse were related to malnutrition risk. The
      screening variables that were used appeared not to predict hospital length of
      stay or discharge destination.

PMID- 15955752
TI  - Why do we have different urinary catheter use in European home care?

PMID- 15955753
TI  - Spirituality and ageing: the health implications of religious belief and
      practice.

PMID- 15955754
TI  - PEG treatment: an increasing dilemma.

PMID- 15955755
TI  - Is stroke unit care portable? A systematic review of the clinical trials.
AB  - BACKGROUND: It is not known if mobile stroke teams can achieve the good results
      seen in trials of geographically discrete stroke wards (stroke units). OBJECTIVE:
      To establish the effectiveness of mobile stroke teams. DESIGN: Systematic review
      of controlled clinical trials that compared peripatetic systems of organised
      stroke care (stroke team care) with alternative hospital services. METHODS:
      Systematic review and meta-analysis (using Cochrane Collaboration methodology and
      involving the primary trialists). Clinical outcomes included death, dependency,
      the need for institutional care and measures of the process of care such as the
      delivery of key investigations and treatments. RESULTS: Six clinical trials
      (1,085 patients) were identified; five (781 patients) compared some form of
      stroke team care with conventional care in general medical wards and one (304
      patients) compared team care with a comprehensive stroke unit. Compared with care
      in general wards, stroke team care improved some aspects of the process of care,
      but clinical outcomes were similar. Compared with a comprehensive stroke unit,
      stroke team patients were significantly less likely to survive (P <0.001), return
      home (P < 0.001) or regain independence (P < 0.0001). Most aspects of the process
      of care were also poorer than in the stroke unit. CONCLUSIONS: Care from a mobile
      stroke team had no major impact on death, dependency or the need for
      institutional care.

PMID- 15955756
TI  - Early assessment by a mobile stroke team: a randomised controlled trial.
AB  - BACKGROUND: There is overwhelming evidence of the effectiveness of specialist
      stroke rehabilitation, but more limited evidence of the effectiveness of
      organised stroke care during the acute phase of stroke. OBJECTIVE: To determine
      the impact on outcome of access to a mobile team during the acute phase of stroke
      among patients admitted to general wards. STUDY POPULATION: 308 patients admitted
      to one of two hospitals within 5 days of the onset of a clinically diagnosed
      stroke. STUDY DESIGN: Randomised controlled trial. STUDY GROUPS: Following
      admission, patients in the intervention arm were visited by members of a mobile
      stroke team who advised clinical staff on appropriate and timely investigation
      and management. They co-ordinated early input from therapy groups and identified
      those ready for transfer to the stroke rehabilitation unit. Patients in the
      control arm were not visited by the mobile stroke team. MAIN OUTCOME MEASURE: All
      cause mortality measured at 6 weeks and 12 months. RESULTS: There was no
      statistically significant difference observed between study groups in mortality
      at 6 weeks (95% CI(adj) -7.4 to 7.4%) nor at 12 months ( 95% CI(adj) -4.1 to
      15.9%). There were also no differences observed between study groups in morbidity
      outcomes or health-related quality of life measured at 12 months. CONCLUSION: The
      trial was terminated before the necessary sample size was collected but findings
      suggest that the mobile stroke team failed to confer significant long-term
      mortality benefit compared with general ward-based care alone.

PMID- 15955757
TI  - Post-discharge home-based support for older cardiac patients: a randomised
      controlled trial.
AB  - BACKGROUND: Hospital and exercise-based cardiac rehabilitation programmes do not
      suit many older patients and home-based rehabilitation may be more effective.
      OBJECTIVE: To evaluate a home-based intervention for patients aged 65 years or
      over discharged home from hospital after emergency admission for suspected
      myocardial infarction. DESIGN: A single-blind randomised controlled trial
      comparing home-based intervention by a nurse with usual care. SUBJECTS: Patients
      aged 65 years or over discharged home after hospitalisation with suspected
      myocardial infarction (n= 324). INTERVENTION: Home-based intervention (n = 163)
      consisted of home visits at 1-2 and 6-8 weeks after hospital discharge by a nurse
      who encouraged compliance with and knowledge of their treatment regimen, offered
      support and guidance about resuming daily activities, and involved other
      community services as appropriate. MEASUREMENTS: Up to 100 days after admission,
      data were collected on deaths, hospital readmissions and use of outpatient
      services. Survivors were sent a postal questionnaire to assess activities of
      daily living and quality of life. RESULTS: At 100 day follow-up there was no
      difference in deaths, activities of daily living or overall quality of life, but
      those in the intervention group scored significantly better on the confidence and
      self-esteem subsections. The intervention group had fewer hospital readmissions
      (35 versus 51, relative risk 0.68, 95% CI 0.47-0.98, P < 0.05) and fewer days of
      hospitalisation after initial discharge (mean difference -1.7, 95% CI -2.09 to 
      1.31, P < 0.05). A total of 42/43 individuals in the intervention group had
      resumed driving at follow-up, compared with 32/43 in the usual care group
      (observed difference between proportions 23%, 95% CI 9-37%, P < 0.05).
      CONCLUSION: Amongst older patients discharged home after hospitalisation for
      suspected myocardial infarction, home-based nurse intervention may improve
      confidence and self-esteem, and reduce early hospital readmissions.

PMID- 15955758
TI  - Prediction of delirium in fractured neck of femur as part of routine preoperative
      nursing care.

PMID- 15955759
TI  - The impact of stroke nurse specialist input on risk factor modification: a
      randomised controlled trial.

PMID- 15955760
TI  - Non-valvular atrial fibrillation and cognitive function--baseline results of a
      longitudinal cohort study.

PMID- 15955761
TI  - Tolerability of spironolactone as adjunctive treatment for heart failure in
      patients over 75 years of age.

PMID- 15955762
TI  - Are depression, anxiety and health beliefs important predictors of older people's
      primary care consulting?

PMID- 15955763
TI  - The effects of positioning after stroke on physiological homeostasis: a review.

PMID- 15955764
TI  - Religious attendance and 12-year survival in older persons.

PMID- 15955765
TI  - Parkinson's tremor mimicking ventricular tachycardia.
AB  - We report the case of an elderly lady with Parkinson's tremor whose
      electrocardiographic (ECG) appearance simulated ventricular tachycardia. As a
      result she underwent unnecessary clinical intervention. We also highlight the
      difficulty in correctly identifying a tremor-induced ECG artefact with regard to
      Parkinson's disease, due to the diverse range of possible clinical scenarios
      presented by patients with this condition.

PMID- 15955766
TI  - Nonagenarian's use of emergency departments.

PMID- 15955767
TI  - Managing the challenge of atrial fibrillation and stroke prevention in older
      people: new drugs or new approaches to improve outcomes?

PMID- 15955768
TI  - Evidence of ageism in the management of acute coronary syndromes.

PMID- 15955770
TI  - Interventions for sarcopenia and muscle weakness in older people.

PMID- 15955772
TI  - Methods to check correct placement of a nasogastric tube: beware of the pitfalls.

PMID- 15955774
TI  - Re: 'Avoidance hierarchies and preferences for anticoagulation--semi-qualitative
      analysis of older patients' views about stroke prevention and the use of
      warfarin'.

PMID- 15955775
TI  - Geriatric wards in acute hospitals.

PMID- 15955776
TI  - Can screening and simple written advice reduce excessive alcohol consumption
      among emergency care patients?
AB  - AIMS: Emergency care patients have an overrepresentation of risky drinkers.
      Despite the evidence on the effectiveness of a short feedback on screening or
      self-help material, most studies performed so far have required considerable time
      from staff and thus been difficult to implement in the real world. The present
      study evaluates the effect of the screening and whether simple written advice has
      any additional effect on risky drinking. METHODS: An alcohol screening routine
      was implemented among injury patients in a Swedish emergency care department.
      Over 12 months, two cohorts were invited to answer an alcohol screening
      questionnaire in the waiting room. In the first 6 months, 771 patients were
      screened without any written advice (cohort A) and in the following 6 months, 563
      were screened and in addition received simple written advice about sensible
      drinking (cohort B). None of the patients received one-to-one feedback. Six
      months after the screening, a follow-up interview by telephone explored the
      changes in drinking. RESULTS: In cohort A 182 (24%) of the patients were defined
      as risky drinkers and in cohort B 125 (22%). Reached at follow-up after 6 months
      were 81 (44%) risky and 278 (47%) non-risky drinkers in cohort A, and 40 (32%)
      risky and 220 (50%) non-risky drinkers in cohort B. The number of patients with
      heavy episodic drinking decreased significantly in cohort A from 76 (94% of the
      risky drinkers) to 49 (59%). In cohort B a similar change was seen from 37 (92%)
      to 27 (68%). Only in cohort B, was a significant increase in readiness to change
      drinking habits seen [from 3 (8%) to 9 (23%)]. The reduction in heavy episodic
      drinking was comparable with previous reports from more extensive interventions.
      However, at the time of follow-up, drinking among non-risky drinkers at baseline
      had increased. When considering the greater numbers of non-risky drinkers, the
      total consumption in the study group increased during the study period.
      CONCLUSIONS: Owing to the reported difficulties of integrating more time
      consuming alcohol interventions in emergency departments, it is suggested that at
      least screening for drinking should be implemented as routine in emergency
      departments. More research is needed in order to establish the optimal balance
      between effective alcohol intervention, and acceptable time and effort
      requirement from staff.

PMID- 15955777
TI  - Should we consider an acceptable drinking level specifically for postmenopausal
      women? Preliminary findings from the postmenopausal health disparities study.
AB  - AIMS: There are substantial neuroendocrine differences between postmenopausal
      (PMP) women and women with cyclic ovarian function; thus there are differences in
      hormonal responses to 'acceptable' levels of drinking, i.e. 7 total weekly drinks
      (TWD). The aim is to evaluate whether alcoholic beverage consumption for PMP
      women should be the same for all women, as is currently the case, or different
      from that for women with cyclic ovarian function. METHODS: Carefully collected
      and cross-checked current drinking data in 318 PMP women from a spectrum of
      racial and ethnic groups have been analysed to determine if a plateau in
      estradiol (E2) levels at a particular alcohol consumption level other than 7 TWD
      can be identified as the drinking level above which no additional benefit in E2
      levels occurs. RESULTS: Levels of E2 are significantly different among abstainers
      and among drinkers within all racial and ethnic groups, with the disturbing
      exception of black PMP women. Although there are significant differences among
      racial and ethnic groups in the proportions of women who drink, there are no
      differences in TWD consumed during the previous month. Between < or =5 TWD and <
      or =6 TWD, a plateau in the correlation of E2 with increasing drinks/week occurs,
      and the range of the unstandardized multiple regression coefficient +/- the
      standard error do not overlap between these same two drinking levels (P < 0.05).
      CONCLUSIONS: Consideration should be given to lowering the acceptable level of
      drinking for PMP women 5 TWD. Additional studies in which sample sizes for each
      minority racial and ethnic are larger need to be performed in the future.

PMID- 15955778
TI  - Divergence of natural killer cell receptor and related molecule in the decidua
      from sporadic miscarriage with normal chromosome karyotype.
AB  - The aim of this cohort study was to investigate immunophenotypic characteristics
      of natural killer (NK) cells by assessing specific molecules expressed in the
      decidua of sporadic miscarriages and induced abortions. The deciduae were
      obtained from 29 consecutively seen women whose pregnancies ended in first
      trimester miscarriages (MS), and the fetal chromosome karyotype of these MS was
      analysed. Additionally, 13 deciduae were obtained from induced abortion (IA) with
      informed consent. The expression of perforin, CD94, CD161, CD158a, CD158b, CD244
      on CD3-CD56+NK cells, and perforin on CD3+CD8+ T cells was analysed by flow
      cytometry. The CD158a (mean+/-SD, 26.2+/-14.7%) and CD94 (50.2+/-25.7%)
      expressions in MS with normal chromosome karyotype (MSNK; n=11) were
      significantly decreased as compared with those (41.5+/-19.5%, 71.4+/-20.4%) in MS
      with abnormal karyotype (MSAK; n=18) and those (44.3+/-21.9%, 80.8+/-17.5%) in IA
      (n=13). Conversely, the perforin expression on CD3-CD8-CD56+NK cells (76.3+/
      11.0%) and CD3+CD8+T cells (30.6+/-9.2%) in MSNK was significantly increased as
      compared with those (66.8+/-16.6%, 23.6+/-8.7%) in MSAK and those (62.9+/-11.6%,
      19.7+/-8.1%) in IA. A positive correlation between CD94 and CD158a expressions on
      NK cells, negative correlations between CD94 on NK cells and perforin on NK
      cells/T cells, and between CD158a on NK cells and perforin on T cells were found
      in the decidua. A divergence of NK cell repertoire in the decidua might be
      related to aetiology of sporadic MSNK.

PMID- 15955779
TI  - IUPred: web server for the prediction of intrinsically unstructured regions of
      proteins based on estimated energy content.
AB  - Intrinsically unstructured/disordered proteins and domains (IUPs) lack a well
      defined three-dimensional structure under native conditions. The IUPred server
      presents a novel algorithm for predicting such regions from amino acid sequences
      by estimating their total pairwise interresidue interaction energy, based on the
      assumption that IUP sequences do not fold due to their inability to form
      sufficient stabilizing interresidue interactions. Optional to the prediction are
      built-in parameter sets optimized for predicting short or long disordered regions
      and structured domains.

PMID- 15955780
TI  - Improving sequence-based fold recognition by using 3D model quality assessment.
AB  - MOTIVATION: The ability of a simple method (MODCHECK) to determine the sequence
      structure compatibility of a set of structural models generated by fold
      recognition is tested in a thorough benchmark analysis. Four Model Quality
      Assessment Programs (MQAPs) were tested on 188 targets from the latest LiveBench
      9 automated structure evaluation experiment. We systematically test and evaluate
      whether the MQAP methods can successfully detect native-like models. RESULTS: We
      show that compared with the other three methods tested MODCHECK is the most
      reliable method for consistently performing the best top model selection and for
      ranking the models. In addition, we show that the choice of model similarity
      score used to assess a model's similarity to the experimental structure can
      influence the overall performance of these tools. Although these MQAP methods
      fail to improve the model selection performance for methods that already
      incorporate protein three dimension (3D) structural information, an improvement
      is observed for methods that are purely sequence-based, including the best
      profile-profile methods. This suggests that even the best sequence-based fold
      recognition methods can still be improved by taking into account the 3D
      structural information. CONTACT: d.jones@cs.ucl.ac.uk

PMID- 15955781
TI  - Statistical analysis of antigen receptor spectratype data.
AB  - MOTIVATION: The effectiveness of vertebrate adaptive immunity depends crucially
      on the establishment and maintenance of extreme diversity in the antigen receptor
      repertoire. Spectratype analysis is a method used in clinical and basic
      immunological settings in which antigen receptor length diversity is assessed as
      a surrogate for functional diversity. The purpose of this paper is to describe
      the systematic derivation and application of statistical methods for the analysis
      of spectratype data. RESULTS: The basic probability model used for spectratype
      analysis is the multinomial model with n, the total number of counts,
      indeterminate. We derive the appropriate statistics and statistical procedures
      for testing hypotheses regarding differences in antigen receptor distributions
      and variable repertoire diversity in different treatment groups. We then apply
      these methods to spectratype data obtained from several healthy donors to examine
      the differences between normal CD4+ and CD8+ T cell repertoires, and to data from
      a thymus transplant patient to examine the development of repertoire diversity
      following the transplant.

PMID- 15955782
TI  - A semantic analysis of the annotations of the human genome.
AB  - The correct interpretation of any biological experiment depends in an essential
      way on the accuracy and consistency of the existing annotation databases. Such
      databases are ubiquitous and used by all life scientists in most experiments.
      However, it is well known that such databases are incomplete and many annotations
      may also be incorrect. In this paper we describe a technique that can be used to
      analyze the semantic content of such annotation databases. Our approach is able
      to extract implicit semantic relationships between genes and functions. This
      ability allows us to discover novel functions for known genes. This approach is
      able to identify missing and inaccurate annotations in existing annotation
      databases, and thus help improve their accuracy. We used our technique to analyze
      the current annotations of the human genome. From this body of annotations, we
      were able to predict 212 additional gene-function assignments. A subsequent
      literature search found that 138 of these gene-functions assignments are
      supported by existing peer-reviewed papers. An additional 23 assignments have
      been confirmed in the meantime by the addition of the respective annotations in
      later releases of the Gene Ontology database. Overall, the 161 confirmed
      assignments represent 75.95% of the proposed gene-function assignments. Only one
      of our predictions (0.4%) was contradicted by the existing literature. We could
      not find any relevant articles for 50 of our predictions (23.58%). The method is
      independent of the organism and can be used to analyze and improve the quality of
      the data of any public or private annotation database.

PMID- 15955783
TI  - FoldIndex: a simple tool to predict whether a given protein sequence is
      intrinsically unfolded.
AB  - An easy-to-use, versatile and freely available graphic web server, FoldIndex is
      described: it predicts if a given protein sequence is intrinsically unfolded
      implementing the algorithm of Uversky and co-workers, which is based on the
      average residue hydrophobicity and net charge of the sequence. FoldIndex has an
      error rate comparable to that of more sophisticated fold prediction methods.
      Sliding windows permit identification of large regions within a protein that
      possess folding propensities different from those of the whole protein.

PMID- 15955784
TI  - HEGESMA: genome search meta-analysis and heterogeneity testing.
AB  - SUMMARY: Heterogeneity and genome search meta-analysis (HEGESMA) is a
      comprehensive software for performing genome scan meta-analysis, a quantitative
      method to identify genetic regions (bins) with consistently increased linkage
      score across multiple genome scans, and for testing the heterogeneity of the
      results of each bin across scans. The program provides as an output the average
      of ranks and three heterogeneity statistics, as well as corresponding
      significance levels. Statistical inferences are based on Monte Carlo permutation
      tests. The program allows both unweighted and weighted analysis, with the weights
      for each study as specified by the user. Furthermore, the program performs
      heterogeneity analyses restricted to the bins with similar average ranks.
      AVAILABILITY: http://biomath.med.uth.gr.

PMID- 15955785
TI  - Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a
      new entity of hereditary colorectal cancer.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically
      defined by familial clustering of colorectal cancer and other associated tumours.
      METHODS: By thorough molecular and clinical evaluation of 41 families, two
      different groups were characterised: group 1, 25 families with truncating
      mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam
      positive families without mutations in these genes and without microsatellite
      instability in their corresponding tumours. RESULTS: Significant clinical
      differences between these two groups were found. Firstly, earlier age of onset
      for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours
      (median 43 v 56 years; p = 0.022) was observed, comparing groups 1 and 2.
      Secondly, 68% of the index colorectal cancers were localised proximally of the
      splenic flexure in group 1 compared with 14% in group 2 (p < 0.010). Thirdly,
      more synchronous and metachronous colorectal (p = 0.017) and extracolorectal
      tumours (p < 0.001) were found in group 1. Fourthly, a higher colorectal
      adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronous or
      metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower
      progression of adenomas to carcinomas. As three mutation negative tumours
      revealed chromosomal instability after comparative genomic hybridisation, these
      tumours may be caused by one or more highly penetrant disease alleles from the
      chromosomal instability pathway. CONCLUSION: These data show that HNPCC includes
      at least two entities with clinical and molecular differences. This will have
      implications for surveillance programmes and for cancer research.

PMID- 15955786
TI  - Polymorphisms in the DLG5 and OCTN cation transporter genes in Crohn's disease.
AB  - BACKGROUND AND AIMS: Recent data suggest identification of causal genetic
      variants for inflammatory bowel disease in the DLG5 gene and in the organic
      cation transporter (OCTN) cluster, both situated in previously described linkage
      regions. PATIENTS AND METHODS: The polymorphisms in DLG5 (113 G-->A, 4136 C-->A,
      and DLG5_e26), SLC22A4 (1672 C-->T), and SLC22A5 (-207 G-->C) were assessed in
      625 patients with Crohn's disease (CD), 363 patients with ulcerative colitis
      (UC), and 1012 healthy controls. Association with disease susceptibility,
      clinical phenotypes, and possible genetic interactions of these polymorphisms
      with disease associated CARD15/NOD2 mutations was analysed. RESULTS: No
      significant association of DLG5 polymorphisms with CD or UC was observed.
      Homozygosity for the OCTN-TC haplotype was associated with an increased CD risk
      (OR = 1.65), which was even greater in the presence of CARD15 mutations. Genotype
      phenotype analysis revealed that this association was particularly strong in
      patients with colonic disease. The TC haplotype was associated with non
      fistulising non-fibrostenotic disease, an earlier age of disease onset, and
      reduced need for surgery. CONCLUSION: Our observations argue against a role of
      DLG5 polymorphisms in the susceptibility for inflammatory bowel disease, whereas
      the OCTN polymorphisms are associated with CD. However, due to the comparable
      weak association observed herein, extended linkage disequilibrium analyses of
      these variants with the IBD5 haplotype tagged single nucleotide polymorphims
      might be advisable before definitive conclusions about their causative role in CD
      can be drawn.

PMID- 15955788
TI  - Analysis of indole-3-butyric acid-induced adventitious root formation on
      Arabidopsis stem segments.
AB  - Root induction by auxins is still not well understood at the molecular level. In
      this study a system has been devised which distinguishes between the two active
      auxins indole-3-butyric acid (IBA) and indole-3-acetic acid (IAA). IBA, but not
      IAA, efficiently induced adventitious rooting in Arabidopsis stem segments at a
      concentration of 10 microM. In wild-type plants, roots formed exclusively out of
      calli at the basal end of the segments. Root formation was inhibited by 10 microM
      3,4,5-triiodobenzoic acid (TIBA), an inhibitor of polar auxin transport. At
      intermediate IBA concentrations (3-10 microM), root induction was less efficient
      in trp1, a tryptophan auxotroph of Arabidopsis with a bushy phenotype but no
      demonstrable reduction in IAA levels. By contrast, two mutants of Arabidopsis
      with measurably higher levels of IAA (trp2, amt1) show root induction
      characteristics very similar to the wild type. Using differential display,
      transcripts specific to the rooting process were identified by devising a
      protocol that distinguished between callus production only and callus production
      followed by root initiation. One fragment was identical to the sequence of a
      putative regulatory subunit B of protein phosphatase 2A. It is suggested that
      adventitious rooting in Arabidopsis stem segments is due to an interaction
      between endogenous IAA and exogenous IBA. In stem explants, residual endogenous
      IAA is transported to the basal end of each segment, thereby inducing root
      formation. In stem segments in which the polar auxin transport is inhibited by
      TIBA, root formation does not occur.

PMID- 15955787
TI  - Accuracy of endoscopic ultrasonography in diagnosing ascites and predicting
      peritoneal metastases in gastric cancer patients.
AB  - BACKGROUND: Preoperative diagnosis of peritoneal metastases (PM) is difficult in
      patients with gastric cancer (GC). AIMS: To assess the accuracy of endoscopic
      ultrasonography (EUS) in diagnosing ascites and its predictability for the
      presence of PM in GC patients. SUBJECTS: Consecutive patients with newly
      diagnosed GC from 1998 to 2004 were studied. METHODS: All patients underwent EUS,
      ultrasound (US), and computed tomography (CT) scan for preoperative staging and
      the presence of ascites. The results were compared with operative findings. The
      diagnosis of PM was confirmed by histopathology or peritoneal fluid cytology.
      RESULTS: A total of 301 patients were recruited and in 250 patients the presence
      of ascites (n = 93) and PM (n = 71) were confirmed. EUS was more sensitive
      (87.1%) than combined US and CT scan examinations (16.1%) and operative findings
      (laparoscopy or laparotomy) (40.9%) in diagnosing ascites. Sensitivity,
      specificity, positive and negative predictive values, and accuracy for predicting
      the presence of PM were 73%, 84%, 64%, 89%, and 81% by EUS; 18%, 99%, 87%, 75%,
      and 76% by combining US and CT scan; and 77%, 94%, 83%, 91%, and 89% by operative
      findings, respectively. In multivariate logistic regression analysis, EUS
      detected ascites was the only significant independent predictor for the presence
      of PM (p<0.001; odds ratio 4.7 (95% confidence interval 2.0-11.2)). CONCLUSION:
      EUS is a sensitive method for diagnosing ascites which is an important predictive
      factor for the presence of PM in GC patients.

PMID- 15955789
TI  - Hydrogen peroxide and expression of hipI-superoxide dismutase are associated with
      the development of secondary cell walls in Zinnia elegans.
AB  - A special form of a CuZn-superoxide dismutase with a high isoelectric point (hipI
      SOD; EC 1.15.1.1) and hydrogen peroxide (H2O2) production were studied during the
      secondary cell wall formation of the inducible tracheary element cell-culture
      system of Zinnia elegans L. Confocal microscopy after labelling with 2',7'
      dichlorofluorescin diacetate showed H2O2 to be located largely in the secondary
      cell walls in developing tracheary elements. Fluorescence-activated cell sorting
      analysis showed there were lower levels of H2O2 in the population containing
      tracheary elements when H2O2 scavengers such as ascorbate, catalase, and reduced
      glutathione were applied to the cell culture. Inhibitors of NADPH oxidase and SOD
      also reduced the amount of H2O2 in the tracheary elements. Furthermore, addition
      of these compounds to cell cultures at the time of tracheary element initiation
      reduced the amount of lignin and the development of the secondary cell walls.
      Analysis of UV excitation under a confocal laser scanning microscope confirmed
      these results. The expression of hipI-SOD increased as the number of tracheary
      elements in the cell culture increased and developed. Additionally,
      immunolocalization of a hipI-SOD isoform during the tracheary element
      differentiation showed a developmental build-up of the protein in the Golgi
      apparatus and the secondary cell wall. These findings suggest a novel hipI-SOD
      could be involved in the regulation of H2O2 required for the development of the
      secondary cell walls of tracheary elements.

PMID- 15955790
TI  - Different ethylene receptors show an increased expression during the ripening of
      strawberries: does such an increment imply a role for ethylene in the ripening of
      these non-climacteric fruits?
AB  - Notwithstanding the economic importance of non-climacteric fruits like grape and
      strawberry, little is known about the mechanisms that regulate their ripening. Up
      to now no growth regulator has emerged with a primary role similar to that played
      by ethylene in the ripening of the climacteric fruits. Strawberries can produce
      ethylene, although in limited amounts. Two cDNAs coding for enzymes of the
      ethylene biosynthetic pathway (i.e. FaACO1 and FaACO2), and three cDNAs encoding
      different ethylene receptors have been isolated. Two receptors (i.e. FaEtr1 and
      FaErs1) belong to the type-I while the third (i.e. FaEtr2) belongs to the type-II
      group. The expression of both the ACO and the receptor-encoding genes has been
      studied in fruits at different stages of development and in fruits treated with
      hormones (i.e. ethylene and the auxin analogue NAA). All the data thus obtained
      have been correlated to the known data about ethylene production by strawberry
      fruits. Interestingly, a good correlation has resulted between the expression of
      the genes described in this work and the data of ethylene production. In
      particular, similarly to what occurs during climacteric fruit ripening, there is
      an increased synthesis of receptors concomitant with the increased synthesis of
      ethylene in strawberries as well. Moreover, the receptors mostly expressed in
      ripening strawberries are the type-II ones, that is those with a degenerate
      histidine-kinase domain. Since the latter domain is thought to establish a weaker
      link to the CTR1 proteins, even the little ethylene produced by ripening
      strawberries might be sufficient to trigger ripening-related physiological
      responses.

PMID- 15955791
TI  - Expression of genes encoding cell wall modifying enzymes is induced by cold
      storage and reflects changes in pear fruit texture.
AB  - Preclimacteric 'Rocha' pears stored under chilling conditions, had a larger
      increase of ACO (1-aminocyclopropane-1-carboxylate oxidase) activity and softened
      faster than those treated with ethylene. Non-treated fruit did not ripen or
      soften, acquired a rubbery texture, and showed barely detectable levels of ACO
      activity. The transcript accumulation of seven genes encoding cell wall modifying
      enzymes was followed during fruit growth, ripening, and senescence, and in fruit
      that failed to ripen, by quantitative real-time PCR. Transcripts from 'Rocha'
      pear polygalacturonase1 and 2 (PcPG1, PcPG2), beta-galactosidase (PcbetaGAL) and
      beta-xylosidase (PcXYL) genes accumulated up to 1000-fold at the climacteric
      onset, while low transcript levels were detected in growing fruit. In fruit that
      did not ripen, this transcript accumulation was lower compared with fruits that
      ripened normally. Transcripts for expansin1 and 2 (PcEXPA1, PcEXPA2) accumulated
      in growing fruit, but about 10-fold more in fruit after rewarming. Xyloglucan
      endotransglucosylase/hydrolase (PcXTH) had the highest basal expression levels in
      all samples, showing only a small increase during fruit growth and ripening.
      PcEXPA2 and PcXTH transcripts accumulated in untreated fruit, 21 d after harvest,
      to levels similar to those of fruit that ripened normally. Since in untreated
      fruit ACO activity was barely detectable, it is likely that the activation of
      these genes might occur at very low ethylene levels. Results suggest that PcXTH
      and PcEXPA2 gene induction might be associated with cell wall maintenance during
      'Rocha' pear development and ripening, while PcEXPA1, PcPG1, PcPG2, PcbetaGAL,
      and PcXYL expression is likely to be related to cell wall disassembly and
      loosening.

PMID- 15955792
TI  - 'I can't do any serious exercise': barriers to physical activity amongst people
      of Pakistani and Indian origin with Type 2 diabetes.
AB  - Type 2 diabetes is at least 4 times more common among British South Asians than
      in the general population. South Asians also have a higher risk of diabetic
      complications, a situation which has been linked to low levels of physical
      activity observed amongst this group. Little is known about the factors and
      considerations which prohibit and/or facilitate physical activity amongst South
      Asians. This qualitative study explored Pakistani (n = 23) and Indian (n = 9)
      patients' perceptions and experiences of undertaking physical activity as part of
      their diabetes care. Although respondents reported an awareness of the need to
      undertake physical activity, few had put this lifestyle advice into practice. For
      many, practical considerations, such as lack of time, were interwoven with
      cultural norms and social expectations. Whilst respondents reported health
      problems which could make physical activity difficult, these were reinforced by
      their perceptions and understandings of their diabetes, and its impact upon their
      future health. Education may play a role in physical activity promotion; however,
      health promoters may need to work with, rather than against, cultural norms and
      individual perceptions. We recommend a realistic and culturally sensitive
      approach, which identifies and capitalizes on the kinds of activities patients
      already do in their everyday lives.

PMID- 15955793
TI  - Immunology of type 1 diabetes.

PMID- 15955794
TI  - Immune response genes in the post-Q-fever fatigue syndrome, Q fever endocarditis
      and uncomplicated acute primary Q fever.
AB  - BACKGROUND: The influence of immune response gene variations on the development
      of chronic complications of Q fever is presently unclear. AIM: To compare the
      frequencies of allelic polymorphisms in immune response genes in different Q
      fever patient groups. DESIGN: Genetic association study. METHODS: We measured the
      frequencies of immune response gene variants in: (i) an expanded group of 31 post
      Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and
      (iii) 22 patients who made an uncomplicated recovery from their initial attack of
      primary acute Q fever, comparing them with various standard control panels from
      the general population. RESULTS: There were significant differences between the
      three Q fever groups. QFS patients differed from both QFE and uncomplicated
      patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2
      genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA
      DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses
      from PBMC stimulated with ligand in short-term culture. QFE showed differences in
      the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF
      alpha receptor II 196R polymorphism. Q fever patients who had made an
      uncomplicated recovery differed from those with QFS or QFE, but were not
      significantly different in allelic frequencies to the control panels. DISCUSSION:
      These immunogenetic differences support the concept of different immune states in
      chronic Q fever, determined by genetic variations in host immune responses,
      rather than by solely properties of Coxiella burnetii.

PMID- 15955795
TI  - Variation in the diagnostic performance of D-dimer for suspected deep vein
      thrombosis.
AB  - BACKGROUND: Numerous studies have evaluated the accuracy of D-dimer in diagnosing
      suspected deep vein thrombosis (DVT), but results are conflicting. AIM: To
      overview estimates of the diagnostic accuracy of D-dimer and identify causes of
      variation. DESIGN: Systematic review, meta-analysis and meta-regression. METHODS:
      We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of
      Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of
      Effectiveness, the ACP Journal Club, citation lists, and contacted manufacturers.
      We selected studies that compared D-dimer to a reference standard in patients
      with suspected DVT. Data were analysed by random effects meta-analysis and meta
      regression. RESULTS: We included 97 studies reporting 198 assays in 99 different
      patient groups. Overall estimated sensitivity and specificity of D-dimer were
      90.5% and 54.7%, but both estimates were subject to significant heterogeneity (p
      < 0.001). Meta-regression identified that some heterogeneity was explained by
      study setting, exclusion criteria, whether recruitment was consecutive or the
      study prospective, whether D-dimer and the reference standard were measured
      blind, and whether the D-dimer threshold was determined a priori. Sensitivity and
      specificity also varied between ELISA (94% and 45% respectively), latex (89% and
      55%) and whole blood agglutination assays (87% and 68%). Sensitivity was higher
      for proximal than distal DVT. Specificity was dependent upon whether clinical
      probability of DVT was high (specificity 51%), intermediate (67%) or low (78%).
      DISCUSSION: D-dimer has good sensitivity, but poor specificity, for DVT.
      Estimates are subject to substantial heterogeneity from various sources. D-dimer
      specificity appears to be strongly dependent upon the pre-test clinical
      probability of DVT.

PMID- 15955796
TI  - Initial oxygen management in patients with an exacerbation of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: The Norfolk and Norwich University Hospital (NNUH) is situated in
      rural Norfolk, and ambulance journey times are often >30 min. Longer ambulance
      journeys could lead to a greater risk of hypercapnia, if inappropriately high
      concentrations of oxygen are given during an exacerbation of COPD. AIM: To
      investigate the effect of high concentration oxygen (HCO, FiO(2) > 0.28) on COPD
      patients, and the outcome of instituting a simple protocol to reduce such
      exposure. DESIGN: Retrospective audit. METHOD: An audit was conducted of all
      patients admitted with an exacerbation of COPD to the NNUH during the 2 months
      from 1 December 2001 to 31 January 2002 (n = 108). Results were shared with
      paramedics, and guidelines agreed for the initial provision of lower
      concentrations of oxygen (LCO, FiO(2) < or = 0.28). A second audit was conducted
      a year later between 1 December 2002 and 31 January 2003 (n = 103). RESULTS: HCO
      caused significant (p < 0.01) acidosis and inappropriately high PaO(2) and
      PaCO(2), compared to initial LCO therapy. There was a significantly increased
      complication rate during admission (p < 0.01) in those COPD patients receiving
      HCO compared to LCO, particularly when ambulance journeys exceeded 30 min. The
      second audit demonstrated a significant (p < 0.001) reduction in the number of
      patients initially receiving HCO, but the complication rate was unaltered.
      DISCUSSION: A simple intervention, such as providing paramedics with 28% Venturi
      masks, can reduce the number of COPD patients exposed to HCO. A randomized
      controlled trial is long overdue to establish whether HCO or LCO as initial
      management is associated with the most favourable prognosis in different hospital
      settings.

PMID- 15955797
TI  - Diagnostic approach to a patient with hyponatraemia: traditional versus
      physiology-based options.
AB  - The usual diagnostic approach to a patient with hyponatraemia is based on the
      clinical assessment of the extracellular fluid (ECF) volume, and laboratory
      parameters such as plasma osmolality, urine osmolality and/or urine sodium
      concentration. Several clinical diagnostic algorithms (CDA) applying these
      diagnostic parameters are available to the clinician. However, the accuracy and
      utility of these CDAs has never been tested. Therefore, we performed a survey in
      which 46 physicians were asked to apply all existing, unique CDAs for
      hyponatraemia to four selected cases of hyponatraemia. The results of this survey
      showed that, on average, the CDAs enabled only 10% of physicians to reach a
      correct diagnosis. Several weaknesses were identified in the CDAs, including a
      failure to consider acute hyponatraemia, the belief that a modest degree of ECF
      contraction can be detected by physical examination supported by routine
      laboratory data, and a tendency to diagnose the syndrome of inappropriate
      secretion of antidiuretic hormone prior to excluding other causes of
      hyponatraemia. We conclude that the typical architecture of CDAs for
      hyponatraemia represents a hierarchical order of isolated clinical and/or
      laboratory parameters, and that they do not take into account the
      pathophysiological context, the mechanism by which hyponatraemia developed and
      the clinical dangers of hyponatraemia. These restrictions are important for
      physicians confronted with hyponatraemic patients and may require them to choose
      different approaches. We therefore conclude this review with the presentation of
      a more physiology-based approach to hyponatraemia, which seeks to overcome some
      of the limitations of the existing CDAs.

PMID- 15955798
TI  - Under-use of beta-blockers in patients with ischaemic heart disease and
      concomitant chronic obstructive pulmonary disease.
AB  - BACKGROUND: Beta-blockers (BB) improve morbidity and mortality in ischaemic heart
      disease. There is a general reluctance to use BB, especially in patients with
      chronic obstructive pulmonary disease (COPD), which is perceived as an absolute
      contraindication. As large numbers of patients are labelled with COPD without
      objective evidence, they may miss out on the benefit from these drugs. AIM: To
      assess the use of BB in patients with COPD admitted with acute coronary syndrome
      (ACS), and to assess the supporting evidence for the diagnosis of COPD in these
      patients. METHOD: Case-note review and retrospective analysis of 457 consecutive
      patients admitted with troponin-positive ACS between October 2002 and October
      2003. RESULTS: Of 457 ACS patients studied, 246 (54%) were discharged on a BB.
      Cardiologists prescribed BB in ACS patients more frequently than did general
      physicians, (70% vs. 30%, respectively). The reasons for withholding BB were: not
      documented 27%, COPD 33%, heart failure 24%, others 16%. Ninety-four patients
      (21%) had a diagnosis of COPD; only 58 (62%) of these had been reviewed by a
      chest physician or had previous pulmonary function tests. Of the 94 patients with
      COPD, only 15 (16%) were prescribed BB during the admission: 9 by cardiologists
      and 6 by non-cardiologists. BB were discontinued in two patients due to an
      increase in dyspnoea. CONCLUSION: Many patients with a diagnosis of COPD have no
      objective evidence to support the diagnosis and are denied the prognostic
      benefits of BB when presenting with ACS. Before withholding beta-blockers, COPD
      and reversibility should be ascertained by pulmonary function testing. The
      overall use of beta-blockers remains sub-optimal and could be improved in this
      setting.

PMID- 15955799
TI  - Leprosy in Britain: 50 years experience in Liverpool.
AB  - BACKGROUND: Leprosy is a chronic infection that presents with varying dermal and
      neurological symptoms, and which can lead to extensive disability and morbidity,
      often with accompanying social stigma. AIM: To review the patients presenting to
      the Liverpool School of Tropical Medicine (LSTM) between 1946 and 2003, looking
      specifically at country of birth and of infection, details of clinical
      presentation, diagnosis, management and reactions. DESIGN: Retrospective record
      review. METHODS: We retrieved all available clinical records for patients seen
      between 1946 and 2003 (n = 50), consisting of letters, hospital and LSTM
      casenotes, and some radiographs and photographs. Any history of tuberculosis or
      diabetes was recorded. RESULTS: Most patients (64%) were born in the Indian
      subcontinent, and most were thought to have contracted the disease there (62%).
      Features at presentation included anaesthetic skin lesions in 19 (36%),
      hypopigmentation in 15 (30%), and peripheral nerve enlargement in 25 (50%).
      Diagnoses were made by a combination of clinical data and biopsy (60%), and slit
      skin smears were positive for acid-fast bacilli in 61% of multibacillary
      patients. Initial presentation was with a leprosy reaction in five cases (10%),
      and reactions were documented in 42% of all patients. Treatments were varied,
      progressing from traditional Eastern medicine to the WHO-approved multidrug
      therapy in use today, with prophylaxis for children and close contacts.
      DISCUSSION: Leprosy remains an important diagnosis to consider in patients with a
      history of work or travel in the tropics, and is a diagnosis with far-reaching
      medical, social and emotional consequences.

PMID- 15955800
TI  - N-terminal connective tissue growth factor is a marker of the fibrotic phenotype
      in scleroderma.
AB  - BACKGROUND: Over-expression of connective tissue growth factor (CTGF) is a
      hallmark of fibrotic disease, including scleroderma. CTGF acts with the pro
      fibrotic cytokine TGFbeta to promote sustained fibrotic responses in vivo.
      Elevated production of CTGF might be responsible for maintenance of the fibrotic
      phenotype in scleroderma. Assays of CTGF or of its fragments are potential non
      invasive measures of the fibrotic response in scleroderma. AIM: To determine the
      utility of whole, N-terminal, and C-terminal CTGF as surrogate markers for
      fibrosis in scleroderma. DESIGN: Cross-sectional controlled study. METHODS:
      Plasma was collected prospectively from 47 scleroderma patients (26 diffuse
      scleroderma, 21 limited scleroderma) and 18 healthy controls. At the same time,
      dermal interstitial fluid was derived by a suction blister technique from the
      lesional skin of scleroderma patients, and from the forearm skin of healthy
      controls. Whole, N-terminal, and C-terminal CTGF were assayed by ELISA, using
      monoclonal antibodies specific for N- and C-terminal epitopes. RESULTS: N
      terminal cleavage products of CTGF were present at elevated levels in the plasma
      and dermal interstitial fluid of scleroderma patients, compared to healthy
      controls. N-terminal CTGF levels in plasma and dermal interstitial fluid
      correlated with severity of skin disease and (negatively) with disease duration.
      Whole and C-terminal CTGF levels were low in blister fluid and plasma levels were
      not elevated in disease. DISCUSSION: These results support a role for CTGF in
      scleroderma-associated fibrosis and the utility of N-terminal CTGF as a marker of
      fibrosis.

PMID- 15955801
TI  - Osteoporosis and atherosclerosis: biological linkages and the emergence of dual
      purpose therapies.
AB  - Osteoporosis and atherosclerosis are both widely prevalent in an ageing
      population, and induce serious morbidities and death. There is growing evidence
      that in addition to their relationship to ageing, osteoporosis and
      atherosclerosis are also linked by biological associations. This article reviews
      their clinical interrelations, discusses the basic biology of bone and the
      arterial wall, and presents five examples that illustrate their biological
      linkages. Current therapeutic approaches emerging from these linkages, including
      statins, bisphosphonates, and the thiazolidinediones, have dual effects on bone
      and the vasculature. Additional therapies derived from experimental studies that
      enhance bone density and reduce atherogenesis hold further promise to diminish
      the morbidity and mortality of osteoporosis and atherosclerosis, with attendant
      benefits to society.

PMID- 15955802
TI  - Human serum IgM glycosylation: identification of glycoforms that can bind to
      mannan-binding lectin.
AB  - The glycoprotein IgM is the major antibody produced in the primary immune
      response to antigens, circulating in the serum both as a pentamer and a hexamer.
      Pentameric IgM has a single J chain, which is absent in the hexamer. The mu
      (heavy) chain of IgM has five N-linked glycosylation sites. Asn-171, Asn-332, and
      Asn-395 are occupied by complex glycans, whereas Asn-402 and Asn-563 are occupied
      by oligomannose glycans. The glycosylation of human polyclonal IgM from serum has
      been analyzed. IgM was found to contain 23.4% oligomannose glycans GlcNAc2Man5-9,
      consistent with 100% occupancy of Asn-402 and 17% occupancy of the variably
      occupied site at Asn-563. Mannan-binding lectin (MBL) is a member of the
      collectin family of proteins, which bind to oligomannose and GlcNAc-terminating
      structures. A commercial affinity chromatography resin containing immobilized MBL
      has been reported to be useful for partial purification of mouse and also human
      IgM. Human IgM glycoforms that bind to immobilized MBL were isolated; these
      accounted for only 20% of total serum IgM. Compared with total serum IgM, the MBL
      binding glycoforms contained 97% more GlcNAc-terminating structures and 8% more
      oligomannose structures. A glycosylated model of pentameric IgM was constructed,
      and from this model, it became evident that IgM has two distinct faces, only one
      of which can bind to antigen, as the J chain projects from the non-antigen
      binding face. Antigen-bound IgM does not bind to MBL, as the target glycans
      appear to become inaccessible once IgM has bound antigen. Antigen-bound IgM
      pentamers therefore do not activate complement via the lectin pathway, but MBL
      might have a role in the clearance of aggregated IgM.

PMID- 15955803
TI  - Antigenic properties of peptide mimotopes of HIV-1-associated carbohydrate
      antigens.
AB  - The glycan shield of the human immunodeficiency virus (HIV) envelope protein
      presents many potential epitopes for vaccine development. To augment immune
      responses to HIV, type 1 (HIV-1), envelope-associated carbohydrate antigens, we
      are defining peptide mimics of HIV-associated carbohydrate antigens that function
      as antigen mimotopes that upon immunization will induce antibodies cross-reactive
      with carbohydrate antigens. We have previously defined peptides with a putative
      sequence tract RYRY that mimic concanavalin A-binding glycans. To imitate the
      multivalent binding of carbohydrates, we compared the avidity of a linear (911)
      and cyclic peptide (D002) reactive with concanavalin A presented in a multiple
      antigen peptide (MAP) format. The affinity of the MAP-D002 peptide was higher
      than that of the peptide MAP-911, whereas the avidity of D002 peptide was lower
      than that of 911. Serum from mice immunized with MAP-911 had lower titer for
      oligomannose-9 than those elicited by MAP-D002 under the same conditions, but
      both immunogens elicited antibodies that can block the binding of GP120 to
      dendritic cells. Antibodies that bind to the studied MAPs were found in a
      preparation of normal human immunoglobulin for intravenous use. Those that were
      purified on 911 bound back to 911 and D002, whereas anti-D002 antibodies were
      specific only for D002. Human antibodies reactive with both mimotopes and with a
      mannosyl preparation were observed to bind to envelope protein. These results
      suggested the potential to fine-tune the antibody response to carbohydrate
      antigens by modifying structural features of peptide mimotope-based immunogens.

PMID- 15955804
TI  - The sarcolemmal calcium pump inhibits the calcineurin/nuclear factor of activated
      T-cell pathway via interaction with the calcineurin A catalytic subunit.
AB  - The calcineurin/nuclear factor of activated T-cell (NFAT) pathway represents a
      crucial transducer of cellular function. There is increasing evidence placing the
      sarcolemmal calcium pump, or plasma membrane calcium/calmodulin ATPase pump
      (PMCA), as a potential modulator of signal transduction pathways. We demonstrate
      a novel interaction between PMCA and the calcium/calmodulin-dependent
      phosphatase, calcineurin, in mammalian cells. The interaction domains were
      located to the catalytic domain of PMCA4b and the catalytic domain of the
      calcineurin A subunit. Endogenous calcineurin activity, assessed by measuring the
      transcriptional activity of its best characterized substrate, NFAT, was
      significantly inhibited by 60% in the presence of ectopic PMCA4b. This inhibition
      was notably reversed by the co-expression of the PMCA4b interaction domain,
      demonstrating the functional significance of this interaction. PMCA4b was,
      however, unable to confer its inhibitory effect in the presence of a
      calcium/calmodulin-independent constitutively active mutant calcineurin A
      suggesting a calcium/calmodulin-dependent mechanism. The modulatory function of
      PMCA4b is further supported by the observation that endogenous calcineurin moves
      from the cytoplasm to the plasma membrane when PMCA4b is overexpressed. We
      suggest recruitment by PMCA4b of calcineurin to a low calcium environment as a
      possible explanation for these findings. In summary, our results offer strong
      evidence for a novel functional interaction between PMCA and calcineurin,
      suggesting a role for PMCA as a negative modulator of calcineurin-mediated
      signaling pathways in mammalian cells. This study reinforces the emerging role of
      PMCA as a molecular organizer and regulator of signaling transduction pathways.

PMID- 15955805
TI  - Characterization of the intraflagellar transport complex B core: direct
      interaction of the IFT81 and IFT74/72 subunits.
AB  - Required for the assembly and maintenance of eukaryotic cilia and flagella,
      intraflagellar transport (IFT) consists of the bidirectional movement of large
      protein particles between the base and the distal tip of the organelle.
      Anterograde movement of particles away from the cell body is mediated by kinesin
      2, whereas retrograde movement away from the flagellar tip is powered by
      cytoplasmic dynein 1b/2. IFT particles contain multiple copies of two distinct
      protein complexes, A and B, which contain at least 6 and 11 protein subunits,
      respectively. In this study, we have used increased ionic strength to remove four
      peripheral subunits from the IFT complex B of Chlamydomonas reinhardtii,
      revealing a 500-kDa core that contains IFT88, IFT81, IFT74/72, IFT52, IFT46, and
      IFT27. This result demonstrates that the complex B subunits, IFT172, IFT80,
      IFT57, and IFT20 are not required for the core subunits to stay associated.
      Chemical cross-linking of the complex B core resulted in multiple IFT81-74/72
      products. Yeast-based two-hybrid and three-hybrid analyses were then used to show
      that IFT81 and IFT74/72 directly interact to form a higher order oligomer
      consistent with a tetrameric complex. Similar analysis of the vertebrate IFT81
      and IFT74/72 homologues revealed that this interaction has been evolutionarily
      conserved. We hypothesize that these proteins form a tetrameric complex,
      (IFT81)2(IFT74/72)2, which serves as a scaffold for the formation of the intact
      IFT complex B.

PMID- 15955806
TI  - A novel mechanism for the suppression of a voltage-gated potassium channel by
      glucose-dependent insulinotropic polypeptide: protein kinase A-dependent
      endocytosis.
AB  - The mechanisms involved in glucose regulation of insulin secretion by ATP
      sensitive (K(ATP)) and calcium-activated (K(CA)) potassium channels have been
      extensively studied, but less is known about the role of voltage-gated (K(V))
      potassium channels in pancreatic beta-cells. The incretin hormone, glucose
      dependent insulinotropic polypeptide (GIP) stimulates insulin secretion by
      potentiating events underlying membrane depolarization and exerting direct
      effects on exocytosis. In the present study, we identified a novel role for GIP
      in regulating K(V)1.4 channel endocytosis. In GIP receptor-expressing HEK293
      cells, GIP reduced A-type peak ionic current amplitude of K(V)1.4 via activation
      of protein kinase A (PKA). Using mutant forms of K(V)1.4 with Ala-Ser/Thr
      substitutions in a potential PKA phosphorylation site, C-terminal phosphorylation
      was shown to be linked to GIP-mediated current amplitude decreases. Proteinase K
      digestion and immunocytochemical studies on mutant K(V)1.4 localization following
      GIP stimulation demonstrated phosphorylation-dependent rapid endocytosis of
      K(V)1.4. Expression of K(V)1.4 protein was also demonstrated in human beta-cells;
      GIP treatment resulting in similar decreases in A-type potassium current peak
      amplitude to those in HEK293 cells. Transient overexpression in INS-1 beta-cells
      (clone 832/13) of wild-type (WT) K(V)1.4, or a T601A mutant form resistant to PKA
      phosphorylation, resulted in reduced glucose-stimulated insulin secretion; WT
      K(V)1.4 overexpression potentiated GIP-induced insulin secretion, whereas this
      response was absent in T601A cells. These results strongly support an important
      novel role for GIP in regulating K(V)1.4 cell surface expression and modulation
      of A-type potassium currents, which is likely to be critically important for its
      insulinotropic action.

PMID- 15955807
TI  - Human T cell leukemia virus envelope binding and virus entry are mediated by
      distinct domains of the glucose transporter GLUT1.
AB  - The glucose transporter GLUT1, a member of the multimembrane-spanning
      facilitative nutrient transporter family, serves as a receptor for human T cell
      leukemia virus (HTLV) infection. Here, we show that the 7 amino acids of the
      extracellular loop 6 of GLUT1 (ECL6) placed in the context of the related GLUT3
      transporter were sufficient for HTLV envelope binding. Glutamate residue 426 in
      ECL6 was identified as critical for binding. However, binding to ECL6 was not
      sufficient for HTLV envelope-driven infection. Infection required two additional
      determinants located in ECL1 and ECL5, which otherwise did not influence HTLV
      envelope binding. Moreover the single N-glycosylation chain located in ECL1 was
      not required for HTLV infection. Therefore, binding involves a discrete
      determinant in the carboxyl terminal ECL6, whereas post-binding events engage
      extracellular sequences in the amino and carboxyl terminus of GLUT1.

PMID- 15955808
TI  - Structural basis for interaction between the Ubp3 deubiquitinating enzyme and its
      Bre5 cofactor.
AB  - The Bre5 protein is a cofactor for the deubiquitinating enzyme Ubp3, and it
      contains a nuclear transfer factor 2 (NTF2)-like protein recognition module that
      is essential for Ubp3 activity. In this study, we report the x-ray crystal
      structure of the Bre5 NTF2-like domain and show that it forms a homodimeric
      structure that is similar to other NTF2-like domains, except for the presence of
      an intermolecular disulfide bond in the crystals. Sedimentation equilibrium
      studies reveal that under non-reducing conditions, the Bre5 NTF2-like domain is
      exclusively dimeric, whereas a disulfide bond-deficient mutant undergoes a
      monomer-dimer equilibrium with a dissociation constant in the midnanomolar range,
      suggesting that dimer formation and possibly also disulfide bond formation may
      modulate Bre5 function in vivo. Using deletion analysis, we also identify a novel
      N-terminal domain of Ubp3 that is necessary and sufficient for interaction with
      Bre5 and use isothermal titration calorimetry to show that Bre5 and Ubp3 form a
      2:1 complex, in contrast to other reported NTF2-like domain/protein interactions
      that form 1:1 complexes. Finally, we employ structure-based mutagenesis to map
      the Ubp3 binding surface of Bre5 to a region near the Bre5 dimer interface and
      show that this binding surface of Bre5 is important for Ubp3 function in vivo.
      Together, these studies provide novel insights into protein recognition by NTF2
      like domains and provide a molecular scaffold for understanding how Ubp3 function
      is regulated by Bre5 cofactor binding.

PMID- 15955809
TI  - A high throughput screen to identify substrates for the ubiquitin ligase Rsp5.
AB  - Ubiquitin-protein ligases (E3s) are implicated in various human disorders and are
      attractive targets for therapeutic intervention. Although most cellular proteins
      are ubiquitinated, ubiquitination cannot be linked directly to a specific E3 for
      a large fraction of these proteins, and the substrates of most E3 enzymes are
      unknown. We have developed a luminescent assay to detect ubiquitination in vitro,
      which is more quantitative, effective, and sensitive than conventional
      ubiquitination assays. By taking advantage of the abundance of purified proteins
      made available by genomic efforts, we screened hundreds of purified yeast
      proteins for ubiquitination, and we identified previously reported and novel
      substrates of the yeast E3 ligase Rsp5. The relevance of these substrates was
      confirmed in vivo by showing that a number of them interact genetically with
      Rsp5, and some were ubiquitinated by Rsp5 in vivo. The combination of this
      sensitive assay and the availability of purified substrates will enable the
      identification of substrates for any purified E3 enzyme.

PMID- 15955810
TI  - Insulin regulates the membrane arrival, fusion, and C-terminal unmasking of
      glucose transporter-4 via distinct phosphoinositides.
AB  - Insulin increases glucose uptake into muscle via glucose transporter-4 (GLUT4)
      translocation to the cell membrane, but the regulated events in GLUT4 traffic are
      unknown. Here we focus on the role of class IA phosphatidylinositol (PI) 3-kinase
      and specific phosphoinositides in the steps of GLUT4 arrival and fusion with the
      membrane, using L6 muscle cells expressing GLUT4myc. To this end, we detected the
      availability of the myc epitope at the cell surface or intravesicular spaces and
      of the cytosol-facing C-terminal epitope, in cells and membrane lawns derived
      from them. We observed the following: (a) Wortmannin and LY294002 at
      concentrations that inhibit class IA PI 3-kinase reduced but did not abate the C
      terminus gain, yet the myc epitope was unavailable for detection unless lawns or
      cells were permeabilized, suggesting the presence of GLUT4myc in docked, unfused
      vesicles. Accordingly, GLUT4myc-containing vesicles were detected by
      immunoelectron microscopy of membranes from cells pretreated with wortmannin and
      insulin, but not insulin or wortmannin alone. (b) Insulin caused greater
      immunological availability of the C terminus than myc epitopes, suggesting that C
      terminus unmasking had occurred. Delivering phosphatidylinositol 3,4,5
      trisphosphate (PI(3,4,5)P(3)) to intact cells significantly increased lawn
      associated myc signal without C terminus gain. Conversely, phosphatidylinositol 3
      phosphate (PI3P) increased the detection of C terminus epitope without any myc
      gain. We propose that insulin regulates GLUT4 membrane arrival, fusion, and C
      terminus unmasking, through distinct phosphoinositides. PI(3,4,5)P(3) causes
      arrival and fusion without unmasking, whereas PI3P causes arrival and unmasking
      without fusion.

PMID- 15955811
TI  - Biphasic functions of the kinase-defective Ephb6 receptor in cell adhesion and
      migration.
AB  - EphB6 is a unique member in the Eph family of receptor tyrosine kinases in that
      its kinase domain contains several alterations in conserved amino acids and is
      catalytically inactive. Although EphB6 is expressed both in a variety of
      embryonic and adult tissues, biological functions of this receptor are largely
      unknown. In the present study, we examined the function of EphB6 in cell adhesion
      and migration. We demonstrated that EphB6 exerted biphasic effects in response to
      different concentrations of the ephrin-B2 ligand; EphB6 promoted cell adhesion
      and migration when stimulated with low concentrations of ephrin-B2, whereas it
      induced repulsion and inhibited migration upon stimulation with high
      concentrations of ephrin-B2. A truncated EphB6 receptor lacking the cytoplasmic
      domain showed monophasic-positive effects on cell adhesion and migration,
      indicating that the cytoplasmic domain is essential for the negative effects.
      EphB6 is constitutively associated with the Src family kinase Fyn. High
      concentrations of ephrin-B2 induced tyrosine phosphorylation of EphB6 through an
      Src family kinase activity. These results indicate that EphB6 can both positively
      and negatively regulate cell adhesion and migration, and suggest that tyrosine
      phosphorylation of the receptor by an Src family kinase acts as the molecular
      switch for the functional transition.

PMID- 15955812
TI  - Dual roles of P2 purinergic receptors in insulin-stimulated leptin production and
      lipolysis in differentiated rat white adipocytes.
AB  - ATP is co-localized with norepinephrine at the sympathetic nerve terminals and
      may be released simultaneously upon neuronal stimulation, which results in
      activation of purinergic receptors. To examine whether leptin synthesis and
      lipolysis are influenced by P2 purinergic receptor activation, the effects of ATP
      and other nucleotides on leptin secretion and glycerol release have been
      investigated in differentiated rat white adipocytes. Firstly, insulin-induced
      leptin secretion was inhibited by nucleotide treatment with the following
      efficacy order: 3'-O-(4-benzoyl)benzoyl ATP (BzATP) > ATP >> UTP. Secondly,
      treatment of adipocytes with ATP increased both intracellular Ca(2+)
      concentration and cAMP content. Intracellular calcium concentration was increased
      by ATP and UTP, but not BzATP, an effect attributed to phospholipase C-coupled
      P2Y(2). On the other hand, cAMP was generated by treatment with BzATP and
      ATPgammaS, but not UTP, indicating functional expression of adenylyl cyclase
      coupled P2Y(11) receptors in white adipocytes. Thirdly, lipolysis was
      significantly activated by BzATP and ATP, which correlated with the
      characteristics of the P2Y(11) subtype. Taken together, the data presented here
      suggest that white adipocytes express at least two different types of P2Y
      receptors and that activation of P2Y(11) receptor might be involved in inhibition
      of leptin production and stimulation of lipolysis, suggesting that purinergic
      transmission can play an important role in white adipocyte physiology.

PMID- 15955813
TI  - Tudor domains bind symmetrical dimethylated arginines.
AB  - The Tudor domain is an approximately 60-amino acid structure motif in search of a
      function. Herein we show that the Tudor domains of the spinal muscular atrophy
      gene product SMN, the splicing factor 30 kDa (SPF30), and the Tudor domain
      containing 3 (TDRD3) proteins interacted with arginine-glycine-rich motifs in a
      methylarginine-dependent manner. The Tudor domains also associated with
      methylarginine-containing cellular proteins, providing evidence that methylated
      arginines represent physiological ligands for this protein module. In addition,
      we report that spliceosomal small nuclear ribonucleoprotein particles core Sm
      proteins accumulated in the cytoplasm when arginine methylation was inhibited
      with adenosine dialdehyde or in the presence of an excessive amount of
      unmethylated arginine-glycine-rich peptides. These data provide in vivo evidence
      in support of a role for arginine methylation in the proper assembly and
      localization of spliceosomal Sm proteins.

PMID- 15955814
TI  - A lipomannan variant with strong TLR-2-dependent pro-inflammatory activity in
      Saccharothrix aerocolonigenes.
AB  - Lipomannans (LMs) are powerful pro-inflammatory lipoglycans found in mycobacteria
      and related genera, however the molecular bases of their activity are not fully
      understood. We report here the isolation and the structural and functional
      characterization of a new lipomannan variant present in the Pseudonocardineae,
      Saccharothrix aerocolonigenes, designated SaeLM. Using a range of chemical
      degradations, NMR experiments, and mass spectrometry analyses, SaeLM revealed a
      mannosylphosphatidyl-myo-inositol (MPI) anchor glycosylated by an original
      carbohydrate structure whereby an (alpha1-->6)-Manp backbone is substituted at
      >80% of the O-2 position by side chains composed of Manp-(alpha1-->2)-Manp
      (alpha1-->. Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry analysis indicated a distribution of SaeLM glyco-forms ranging from
      19 to 61 Manp units, which centered on species containing 37 or 40 Manp units.
      SaeLM induced a Toll-like receptor 2 (TLR-2)-dependent production of tumor
      necrosis factor-alpha (TNF-alpha) by human THP-1 monocyte/macrophage cell lines
      and interestingly was found to be the strongest inducer of this pro-inflammatory
      cytokine when compared with other LAM/LM-like molecules. We previously
      established that a linear (alpha1-->6)-Manp chain, linked to the MPI anchor, is
      sufficient in providing pro-inflammatory activity. We demonstrate here that by
      adding side chains and increasing their size, one may potentiate this activity.
      These findings should enable a better understanding of the structure/function
      relationships of TLR-2-dependent lipoglycan signaling.

PMID- 15955815
TI  - Down-regulation of 7SL RNA expression and impairment of vesicular protein
      transport pathways by Leishmania infection of macrophages.
AB  - The parasitic protozoan Leishmania specifically manipulates the expression of
      host macrophage genes during initial interactions, as revealed by mRNA
      differential display reverse transcription-PCR and cDNA microarray analyses. The
      genes that are down-regulated in mouse (J774G8) or human (U937) macrophages upon
      exposure to Leishmania include small RNA transcripts from the short interspersed
      element sequences. Among the short interspersed element RNAs that are down
      regulated is 7SL RNA, which is the RNA component of the signal recognition
      particle. Because the microbicidal functions of macrophages profoundly count on
      vesicular protein transport processes, down-regulation of 7SL RNA may be
      significant in the establishment of infection by Leishmania in macrophage
      phagolysosomes. To evaluate whether down-regulation of 7SL RNA results in
      inhibition of signal recognition particle-mediated vesicular protein transport
      processes, we have tested and found that the targeting of proteins to the
      endoplasmic reticulum and plasma membrane and the secretion of proteins by
      macrophages are compromised in Leishmania-infected J774G8 and U937 cells.
      Knocking down 7SL RNA using small interfering RNA mimicked the effect of exposure
      of macrophages to Leishmania. The overexpression of 7SL RNA in J774G8 or U937
      cells made these cells resistant to Leishmania infection, suggesting the possible
      biological significance of down-regulation of 7SL RNA synthesis in the
      establishment of infection by Leishmania. We conclude that Leishmania down
      regulates 7SL RNA in macrophages to manipulate the targeting of many proteins
      that use the vesicular transport pathway and thus favors its successful
      establishment of infection in macrophages.

PMID- 15955816
TI  - Cooperation between small nuclear RNA-activating protein complex (SNAPC) and TATA
      box-binding protein antagonizes protein kinase CK2 inhibition of DNA binding by
      SNAPC.
AB  - Protein kinase CK2 regulates RNA polymerase III transcription of human U6 small
      nuclear RNA (snRNA) genes both negatively and positively depending upon whether
      the general transcription machinery or RNA polymerase III is preferentially
      phosphorylated. Human U1 snRNA genes share similar promoter architectures as that
      of U6 genes but are transcribed by RNA polymerase II. Herein, we report that CK2
      inhibits U1 snRNA gene transcription by RNA polymerase II. Decreased levels of
      endogenous CK2 correlates with increased U1 expression, whereas CK2 associates
      with U1 gene promoters, indicating that it plays a direct role in U1 gene
      regulation. CK2 phosphorylates the general transcription factor small nuclear RNA
      activating protein complex (SNAP(C)) that is required for both RNA polymerase II
      and III transcription, and SNAP(C) phosphorylation inhibits binding to snRNA gene
      promoters. However, restricted promoter access by phosphorylated SNAP(C) can be
      overcome by cooperative interactions with TATA-box-binding protein at a U6
      promoter but not at a U1 promoter. Thus, CK2 may have the capacity to
      differentially regulate U1 and U6 transcription even though SNAP(C) is
      universally utilized for human snRNA gene transcription.

PMID- 15955817
TI  - Experimental and in silico analyses of glycolytic flux control in bloodstream
      form Trypanosoma brucei.
AB  - A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was
      developed previously on the basis of all available enzyme kinetic data (Bakker,
      B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol.
      Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular
      metabolite concentrations as measured in non-growing trypanosomes and the major
      contribution to the flux control exerted by the plasma membrane glucose
      transporter. Surprisingly, a large overcapacity was predicted for hexokinase
      (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our
      further analysis of the control of glycolytic flux in bloodstream form T. brucei.
      First, the model was optimized and extended with recent information about the
      kinetics of enzymes and their activities as measured in lysates of in vitro
      cultured growing trypanosomes. Second, the concentrations of five glycolytic
      enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes
      were changed by RNA interference. The effects of the knockdown of these enzymes
      on the growth, activities, and levels of various enzymes and glycolytic flux were
      studied and compared with model predictions. Data thus obtained support the
      conclusion from the in silico analysis that HXK, PFK, and PYK are in excess,
      albeit less than predicted. Interestingly, depletion of PFK and enolase had an
      effect on the activity (but not, or to a lesser extent, expression) of some other
      glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like
      organelles harboring the first seven enzymes of the glycolytic pathway of
      trypanosomes) and in the cytosol were affected. These data suggest the existence
      of novel regulatory mechanisms operating in trypanosome glycolysis.

PMID- 15955818
TI  - Structure of plant photosystem I revealed by theoretical modeling.
AB  - Photosystem (PS) I is a large membrane protein complex vital for oxygenic
      photosynthesis, one of the most important biological processes on the planet. We
      present an "atomic" model of higher plant PSI, based on theoretical modeling
      using the recent 4.4 angstroms x-ray crystal structure of PSI from pea. Because
      of the lack of information on the amino acid side chains in the x-ray structural
      model and the high cofactor content in this system, novel modeling techniques
      were developed. Our model reveals some important structural features of plant PSI
      that were not visible in the crystal structure, and our model sheds light on the
      evolutionary relationship between plant and cyanobacterial PSI.

PMID- 15955819
TI  - Interdomain communication in hepatitis C virus polymerase abolished by small
      molecule inhibitors bound to a novel allosteric site.
AB  - The hepatitis C virus (HCV) polymerase is required for replication of the viral
      genome and is a key target for therapeutic intervention against HCV. We have
      determined the crystal structures of the HCV polymerase complexed with two indole
      based allosteric inhibitors at 2.3- and 2.4-Angstroms resolution. The structures
      show that these inhibitors bind to a site on the surface of the thumb domain. A
      cyclohexyl and phenyl ring substituents, bridged by an indole moiety, fill two
      closely spaced pockets, whereas a carboxylate substituent forms a salt bridge
      with an exposed arginine side chain. Interestingly, in the apoenzyme, the
      inhibitor binding site is occupied by a small alpha-helix at the tip of the N
      terminal loop that connects the fingers and thumb domains. Thus, these molecules
      inhibit the enzyme by preventing formation of intramolecular contacts between
      these two domains and consequently precluding their coordinated movements during
      RNA synthesis. Our structures identify a novel mechanism by which a new class of
      allosteric inhibitors inhibits the HCV polymerase and open the way to the
      development of novel antiviral agents against this clinically relevant human
      pathogen.

PMID- 15955820
TI  - Varicella-zoster virus IE63 protein phosphorylation by roscovitine-sensitive
      cyclin-dependent kinases modulates its cellular localization and activity.
AB  - During the first stage of Varicella-Zoster virus (VZV) infection, IE63 (immediate
      early 63 protein) is mostly expressed in the nucleus and also slightly in the
      cytoplasm, and during latency, IE63 localizes in the cytoplasm quite exclusively.
      Because phosphorylation is known to regulate various cellular mechanisms, we
      investigated the impact of phosphorylation by roscovitine-sensitive cyclin
      dependent kinase (RSC) on the localization and functional properties of IE63. We
      demonstrated first that IE63 was phosphorylated on Ser-224 in vitro by CDK1 and
      CDK5 but not by CDK2, CDK7, or CDK9. Furthermore, by using roscovitine and CDK1
      inhibitor III (CiIII), we showed that CDK1 phosphorylated IE63 on Ser-224 in
      vivo. By mutagenesis and the use of inhibitors, we demonstrated that
      phosphorylation on Ser-224 was important for the correct localization of the
      protein. Indeed, the substitution of these residues by alanine led to an
      exclusive nuclear localization of the protein, whereas mutations into glutamic
      acid did not modify its subcellular distribution. When transfected or VZV
      infected cells were treated with roscovitine or CiIII, an exclusive nuclear
      localization of IE63 was also observed. By using a transfection assay, we also
      showed that phosphorylation on Ser-224 and Thr-222 was essential for the down
      regulation of the basal activity of the VZV DNA polymerase gene promoter.
      Similarly, roscovitine and CiIII impaired these properties of the wild-type form
      of IE63. These observations clearly demonstrated the importance of CDK1-mediated
      IE63 phosphorylation for a correct distribution of IE63 between both cellular
      compartments and for its repressive activity toward the promoter tested.

PMID- 15955822
TI  - Leukocyte function-associated antigen 1-mediated adhesion stability is
      dynamically regulated through affinity and valency during bond formation with
      intercellular adhesion molecule-1.
AB  - Neutrophil rolling and transition to arrest on inflamed endothelium are
      dynamically regulated by the affinity of the beta(2) integrin CD11a/CD18
      (leukocyte function associated antigen 1 (LFA-1)) for binding intercellular
      adhesion molecule (ICAM)-1. Conformational shifts are thought to regulate
      molecular affinity and adhesion stability. Also critical to adhesion efficiency
      is membrane redistribution of active LFA-1 into dense submicron clusters where
      multimeric interactions occur. We examined the influences of affinity and
      dimerization of LFA-1 on LFA-1/ICAM-1 binding by engineering a cell-free model in
      which two recombinant LFA-1 heterodimers are bound to respective Fab domains of
      an antibody attached to latex microspheres. Binding of monomeric and dimeric ICAM
      1 to dimeric LFA-1 was measured in real time by fluorescence flow cytometry. ICAM
      1 dissociation kinetics were measured while LFA-1 affinity was dynamically
      shifted by the addition of allosteric small molecules. High affinity LFA-1
      dissociated 10-fold faster when bound to monomeric compared with dimeric ICAM-1,
      corresponding to bond lifetimes of 25 and 330 s, respectively. Downshifting LFA-1
      into an intermediate affinity state with the small molecule I domain allosteric
      inhibitor IC487475 decreased the difference in dissociation rates between
      monomeric and dimeric ICAM-1 to 4-fold. When LFA-1 was shifted into the low
      affinity state by lovastatin, both monomeric and dimeric ICAM-1 dissociated in
      less than 1 s, and the dissociation rates were within 50% of each other. These
      data reveal the respective importance of LFA-1 affinity and proximity in tuning
      bond lifetime with ICAM-1 and demonstrate a nonlinear increase in the bond
      lifetime of the dimer versus the monomer at higher affinity.

PMID- 15955823
TI  - A new functional role of the fibrinogen RGD motif as the molecular switch that
      selectively triggers integrin alphaIIbbeta3-dependent RhoA activation during cell
      spreading.
AB  - A number of RGD-type integrins rely on a synergistic site in addition to the
      canonical RGD site for ligand binding and signaling, although it is still unclear
      whether these two recognition sites function independently, synergistically, or
      competitively. Experimental evidence has suggested that fibrinogen binding to the
      RGD-type integrin alphaIIbbeta3 occurs exclusively through the synergistic
      gamma(400-411) sequence, thus questioning the functional role of the RGD
      recognition site. Here we have investigated the respective role of the fibrinogen
      gamma(400-411) sequence and the RGD motif in the molecular events leading to
      ligand-induced alphaIIbbeta3-dependent Chinese hamster ovary (CHO) cell or
      platelet spreading, by using intact fibrinogen and well characterized plasmin
      generated fibrinogen fragments containing either the RGD motif (fragment C) or
      the gamma(400-411) sequence (fragment D), and CHO cells expressing resting wild
      type (alphaIIbbeta3wt), constitutively active (alphaIIbbeta3T562N), or non
      functional (alphaIIbbeta3D119Y) receptors. Our data provide evidence that the
      gamma(400-411) site by itself is able to initiate alphaIIbbeta3 clustering and
      recruitment of intracellular proteins to early focal complexes, mediating cell
      attachment, FAK phosphorylation, and Rac1 activation, while the RGD motif
      subsequently acts as a molecular switch on the beta3 subunit to trigger cell
      spreading. More importantly, we show that the premier functional role of the RGD
      site is not to reinforce cell attachment but, rather, to imprint a conformational
      change on the beta3 subunit leading to maximal RhoA activation and actin
      cytoskeleton organization in CHO cells as well as in platelets. Finally,
      alphaIIbbeta3-dependent RhoA stimulation and cell spreading, but not cell
      attachment, are Src-dependent and phosphoinositide 3-kinase-independent and are
      inhibited by the Src antagonist PP2.

PMID- 15955821
TI  - Characterization of a thermostable UvrD helicase and its participation in
      helicase-dependent amplification.
AB  - Helicase-dependent amplification (HDA) is an isothermal in vitro DNA
      amplification method based upon the coordinated actions of helicases to separate
      double-stranded DNA and DNA polymerases to synthesize DNA. Previously, a
      mesophilic form of HDA (mHDA) utilizing the Escherichia coli UvrD helicase, DNA
      polymerase I Klenow fragment, two accessory proteins, MutL and single-stranded
      DNA-binding protein (SSB), was developed (1). In an effort to improve the
      specificity and performance of HDA, we have cloned and purified a thermostable
      UvrD helicase (Tte-UvrD) and the mutL homolog (Tte-MutL) from Thermoanaerobacter
      tengcongensis. Characterization of the Tte-UvrD helicase shows that it is stable
      and active from 45 to 65 degrees C. We have found that the Tte-UvrD helicase
      unwinds blunt-ended DNA duplexes as well as substrates possessing 3'- or 5'-ssDNA
      tails. Tte-UvrD was used to develop athermophilichelicase-dependent amplification
      (tHDA) system to selectively amplify target sequences at 60-65 degrees C. The
      tHDA system is more efficient than mHDA, displaying heightened amplification
      sensitivity without the need for the MutL and SSB accessory proteins.
      Amplification independent of MutL corresponds with studies demonstrating that
      maximal Tte-UvrD helicase activity does not require the mutL homolog. The tHDA
      system allows for rapid amplification and detection of targets present in genomic
      DNA. The expeditious nature and simplistic design of the tHDA platform makes the
      technology ideal for use in diagnostic applications requiring rapid
      identification of organisms at the point-of-need.

PMID- 15955824
TI  - mu-Calpain regulates receptor activator of NF-kappaB ligand (RANKL)-supported
      osteoclastogenesis via NF-kappaB activation in RAW 264.7 cells.
AB  - To clarify the role of calpain in the receptor activator of NF-kappaB ligand
      (RANKL)-supported osteoclastogenesis, RANKL-induced calpain activation was
      examined by using murine RAW 264.7 cells and bone marrow-derived
      monocyte/macrophage progenitors. We found that calpain activity increased in
      response to RANKL in both cell types based on alpha-spectrinolysis and that mu
      calpain, rather than m-calpain, was activated during RANKL-supported
      osteoclastogenesis in RAW 264.7 cells. Overexpression of mu-calpain clearly
      augmented RANKL-supported osteoclastogenesis in RAW 264.7 cells, thereby
      implicating its pivotal role in this process. Cell-permeable calpain inhibitors,
      including calpastatin and calpeptin, were sufficient to suppress RANKL-supported
      osteoclastogenesis based on decreased expression of the osteoclastogenic marker,
      matrix metalloproteinase 9, and the generation of tartrate-resistant acid
      phosphatase-positive multinucleated cells in both cell types. Calpain inhibitors
      suppressed NF-kappaB activation via inhibition of the cleavage of inhibitor of NF
      kappaB(IkappaBalpha)in RAW 264.7 cells. Taken together, our findings suggest that
      mu-calpain is essential to the regulation of RANKL-supported osteoclastogenesis
      via NF-kappaB activation.

PMID- 15955825
TI  - Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral
      blood and cord blood: proliferation, Oct4 expression, and plasticity.
AB  - In this study, we used a common procedure to assess the potential of mobilized
      peripheral blood (MPB) and umbilical cord blood (UCB) as sources of mesenchymal
      stem cells (MSCs) in comparison with bone marrow (BM). We tested three methods:
      plastic adhesion supplemented with 5% of BM-MSC conditioned medium,
      unsupplemented plastic adhesion, and selection of CD133-positive cells. MSCs
      derived from MPB or UCB are identified by their positive expression of
      mesenchymal (SH2, SH3) and negative expression of hematopoietic markers (CD14,
      CD34, CD45, HLA-DR). We observed that the CD133-positive cell fraction contains
      more MSCs with high proliferative potential. Placed in appropriate conditions,
      these cells proved their capacity to differentiate into adipocytes, osteocytes,
      chondrocytes, and neuronal/glial cells. MPB- and UCB-MSCs express Oct4, a
      transcriptional binding factor present in undifferentiated cells with high
      proliferative capacity. The selection of CD133-positive cells enabled us to
      obtain a homogeneous population of MSCs from UCB and MPB. These sources may have
      a major clinical importance thanks to their easy accessibility.

PMID- 15955826
TI  - Hematopoietic progenitor cells and cellular microenvironment: behavioral and
      molecular changes upon interaction.
AB  - Cell-cell contact between stem cells and cellular determinants of the
      microenvironment plays an essential role in controlling cell division. Using
      human hematopoietic progenitor cells (CD34+/CD38-) and a stroma cell line
      (AFT024) as a model, we have studied the initial behavioral and molecular sequel
      of this interaction. Time-lapse microscopy showed that CD34+/CD38- cells actively
      migrated toward and sought contact with stroma cells and 30% of them adhered
      firmly to AFT024 stroma through the uropod. CD44 and CD34 are colocalized at the
      site of contact. Gene expression profiles of CD34+/CD38- cells upon cultivation
      with or without stroma for 16, 20, 48, or 72 hours were analyzed using our human
      genome cDNA microarray. Chk1, egr1, and cxcl2 were among the first genes
      upregulated within 16 hours. Genes with the highest upregulation throughout the
      time course included tubulin genes, ezrin, c1qr1, fos, pcna, mcm6, ung, and
      dnmt1, genes that play an essential role in reorganization of the cytoskeleton
      system, stabilization of DNA, and methylation patterns. Our results demonstrate
      directed migration of CD34+/CD38- cells toward AFT024 and adhesion through the
      uropod and that upon interaction with supportive stroma, reorganization of the
      cytoskeleton system, regulation of cell division, and maintenance of genetic
      stability represent the most essential steps.

PMID- 15955827
TI  - Derivation and growing human embryonic stem cells on feeders derived from
      themselves.
AB  - Human embryonic stem cells (hESCs) are pluripotent. They have the potential to
      differentiate into every cell type of an organism. Since many human somatic cell
      types have the ability to support the growth of hESCs, cells differentiated from
      hESCs may also be able to support the growth of themselves. We tested this
      hypothesis by growing hESCs on feeders derived from themselves and demonstrated
      that such feeders did constitute an environment suitable for the derivation and
      long-term growth of hESCs. hESCs maintained in this system expressed all the
      markers indicative of the undifferentiated state and gave rise to cell types
      representative of all three primary germ layers upon differentiation. By
      modifying the genome of hESCs, feeders with special features can be derived and
      mass produced. The system will facilitate large-scale production of hESCs in a
      standardized animal pathogen-free environment.

PMID- 15955828
TI  - Growth hormone-induced stimulation of multilineage human hematopoiesis.
AB  - Growth hormone (GH) has been shown to have significant positive effects on hemato
      lymphopoiesis in rodent models and, more recently, to increase thymic mass and
      circulating naive CD4+ T cells in humans infected with the human immunodeficiency
      virus, type 1. To determine whether the latter effects on human T lymphopoiesis
      might be due, at least in part, to effects on the bone marrow (BM), we examined
      the specific effects of GH and its proximal mediator, insulin-like growth factor
      I (IGF-I), on human multilineage hematopoiesis in fetal BM (FBM). Using in vitro
      analysis, we found that GH and IGF-I each stimulated the expansion of primitive
      multilineage CD34+CD38- hematopoietic progenitor cells and increased yields of
      several hematopoietic subpopulations, including CD34+CD38+CD10+ lymphoid
      progenitor cells. Additionally, GH and IGF-I had direct effects on FBM stromal
      elements, inducing the expansion of myeloid-like CD45+CD14+ FBM stromal cells and
      enhancing production of the hematopoietic cytokine interleukin-3 by fibroblast
      like CD45-CD10+ FBM stromal cells. Surface expression of GH and type-I IGF
      receptors correlated with the observed biologic responses to these hormones.
      Whereas GH enhanced the proliferation of FBM progenitors and stroma, IGF-I
      exerted a predominantly antiapoptotic effect. Finally, both GH and IGF-I
      stimulated the generation of hematopoietic colony forming cells. These findings
      identify specific targets of GH and IGF-I within human FBM, and demonstrate
      direct and indirect effects that may contribute to GH-mediated enhancement of
      human hemato-lymphopoiesis.

PMID- 15955829
TI  - Expression and potential role of fibroblast growth factor 2 and its receptors in
      human embryonic stem cells.
AB  - Although the detection of several components of the fibroblast growth factor
      (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported,
      the functionality of that pathway and effects on cell fate decisions are yet to
      be established. In this study we characterized expression of FGF-2, the
      prototypic member of the FGF family, and its receptors (FGFRs) in
      undifferentiated and differentiating hESCs; subsequently, we analyzed the effects
      of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have
      determined that undifferentiated hESCs are abundant in several molecular-mass
      isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged
      under conditions that induce hESC differentiation. Significantly, FGF-2 is
      released by hESCs into the medium, suggesting an autocrine activity. Expression
      of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being
      the most abundant species and other receptors showing lower expression in the
      following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of
      differentiation is accompanied by profound changes in FGFR expression,
      particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF
      2, extracellular signal-regulated kinases are phosphorylated and thereby
      activated. However, the presence or absence of exogenous FGF-2 does not
      significantly affect the proliferation of hESCs. Instead, increased concentration
      of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in
      culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether
      FGF-2 that is released by hESCs exerts its activities via autocrine pathways.
      Strikingly, the resultant inhibition of FGFR suppresses activation of downstream
      protein kinases and causes rapid cell differentiation, suggesting an involvement
      of autocrine FGF signals in the maintenance of proliferating hESCs in the
      undifferentiated state. In conclusion from our data, we propose that this
      endogenous FGF signaling pathway can be implicated in self-renewal or
      differentiation of hESCs.

PMID- 15955830
TI  - Homologous feeder cells support undifferentiated growth and pluripotency in
      monkey embryonic stem cells.
AB  - In the present study, five homologous feeder cell lines were developed for the
      culture and maintenance of rhesus monkey embryonic stem cells (rESCs). Monkey ear
      skin fibroblasts (MESFs), monkey oviductal fibroblasts (MOFs), monkey follicular
      granulosa fibroblast-like (MFG) cells, monkey follicular granulosa epithelium
      like (MFGE) cells, and clonally derived fibroblasts from MESF (CMESFs) were
      established and compared with the ability of mouse embryonic fibroblasts (MEFs)
      to support rESC growth. MESF, MOF, MFG, and CMESF cells, but not MFGE cells, were
      as good as or better than MEFs in supporting undifferentiated growth while
      maintaining the differentiation potential of the rESCs. In an effort to
      understand the unique properties of supportive feeder cells, expression levels
      for a number of candidate genes were examined. MOF, MESF, and MEF cells highly
      expressed leukemia inhibitory factor, ciliary neurotrophic factor, basic
      fibroblast growth factor, stem cell factor, transforming growth factor beta1,
      bone morphogenetic protein 4, and WNT3A, whereas WNT2, WNT4, and WNT5A were
      downregulated, compared with MFGE cells. Additionally, all monkey feeder cell
      lines expressed Dkk1 and LRP6, antagonists of the WNT signaling pathway, but not
      WNT1, WNT8B, or Dkk2. rESCs grown on homologous feeders maintained normal
      karyotypes, displayed the characteristics of ESCs, including morphology, alkaline
      phosphatase, Oct4, the cell surface markers stage-specific embryonic antigen
      (SSEA)-3, SSEA-4, tumor-related antigen (TRA)-1-60, and TRA-1-81, and formed
      cystic embryoid bodies in vitro that included differentiated cells representing
      the three major germ layers. These results indicate that the four homologous
      feeder cell lines can be used to support the undifferentiated growth and
      maintenance of pluripotency in rESCs.

PMID- 15955831
TI  - Transcriptional profiling of human hematopoiesis during in vitro lineage-specific
      differentiation.
AB  - To better understand the transcriptional program that a ccompanies orderly
      lineage-specific hematopoietic differentiation, we performed serial
      oligonucleotide microarray analysis of human normal CD34+ bone marrow cells
      during lineage-specific differentiation. CD34+ bone marrow cells isolated from
      healthy individuals were selectively stimulated in vitro with the cytokines
      erythropoietin (EPO), thrombopoietin (TPO), granulocyte colony-stimulating factor
      (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF). Cells
      from each of the lineages were harvested after 4, 7, and 11 days of culture for
      expression profiling. Gene expression was analyzed by oligonucleotide microarrays
      (HG-U133A; Affymetrix, Santa Clara, CA). Experiments were done in triplicates. We
      identified 258 genes that are consistently upregulated or downregulated during
      the course of lineage-specific differentiation within each specific lineage
      (horizontal change). In addition, we identified 52 genes that contributed to a
      specific expression profile, yielding a genetic signature specific for successive
      stages of differentiation within each of the three lineages. Analysis of
      horizontal changes selected 21 continuously upregulated genes for EPO-induced
      differentiation (including GTPase activator proteins RAP1GA1 and ARHGAP8, which
      regulate small Rho GTPases), 21 for G-CSF-induced/GM-CSF-induced differentiation,
      and 91 for TPO-induced differentiation (including DLK1, of which the role in
      normal hematopoiesis is not defined). During the lineage-specific
      differentiation, 58 (erythropoiesis), 30 (granulopoiesis), and 37
      (thrombopoiesis) genes were significantly downregulated, respectively. The
      expression of selected genes was confirmed by real-time polymerase chain
      reaction. Our data encompass the first extensive transcriptional profile of human
      hematopoiesis during in vitro lineage-specific differentiation.

PMID- 15955832
TI  - Comparative analysis of sequence-specific DNA recombination systems in human
      embryonic stem cells.
AB  - The great potential of human embryonic stem cells (hESCs) in basic research,
      regenerative medicine, and gene therapy is widely recognized. Controlled
      manipulation of hESC genomes through sequence-specific DNA recombination (SSR)
      may play a significant role in future hESC applications. However, very little is
      known about the functionality of SSR systems in hESCs. We demonstrate here that
      mutant phage lambda integrase, phage P1 Cre recombinase, and mutant gammadelta
      resolvase displayed distinct activities on episomal recombination substrates.
      Interestingly, cofactor-independent lambda integrase catalyzed the integrative
      pathway five times more efficiently than the excisive pathway. Such a degree of
      directionality in hESCs could be explored for sequential gene insertions into
      predetermined genomic sequences. We also report an improved, easy-to-use plasmid
      transfection system that employs silica microspheres and, in combination with
      SSR, could be applied to hESC genome engineering.

PMID- 15955833
TI  - Development of functional neurons from postnatal stem cells in vitro.
AB  - In order for stem cells to fulfill their clinical promise, we must understand
      their developmental transitions and it must be possible to control the
      differentiation of stem cells into specific cell fates. To understand the
      mechanism of the sequential restriction and multipotency of stem cells, we have
      established culture conditions that allow the differentiation of multipotential
      neural stem cells from postnatal stem cells. We used immunocytochemistry,
      fluorescence microscopy, and calcium imaging to demonstrate that progeny of adult
      rat neural stem cells develop into functional neurons that release excitatory
      neurotransmitters. We also found that the nontoxic heavy chain fragment of
      tetanus toxin, a toxin that targets neurons with high specificity, retained the
      specificity toward neural stem cell-derived neurons. These studies show that
      neural stem cells derived from adult tissues retain the potential to
      differentiate into functional neurons with morphological and functional
      properties of mature central nervous system neurons.

PMID- 15955834
TI  - Temporal expression patterns and corresponding protein inductions of early
      responsive genes in rabbit bone marrow-derived mesenchymal stem cells under
      cyclic compressive loading.
AB  - Our recent study suggested that cyclic compressive loading may promote
      chondrogenesis of rabbit bone-marrow mesenchymal stem cells (BM-MSCs) in agarose
      cultures through the transforming growth factor (TGF)-beta signaling pathway. It
      has been shown that the activating protein 1 (AP-1) (Jun-Fos) complex mediated
      autoinduction of TGF-beta1 and its binding activity was essential for promoting
      chondrogenesis of mesenchymal cells, whereas Sox9 was identified as an essential
      transcription factor for chondrogenesis of embryonic mesenchymal cells. The
      objective of this study was to examine temporal expression patterns of early
      responsive genes (Sox9, c-Fos, c-Jun, and TGF-beta type I and II receptors) and
      induction of their corresponding proteins in agarose culture of rabbit BM-MSCs
      subjected to cyclic compressive loading. The rabbit BM-MSCs were obtained from
      the tibias and femurs of New Zealand White rabbits. Cell-agarose constructs were
      made by suspending BM-MSCs in 2% agarose gel (10(7) cells/ml) for cyclic,
      unconfined compression tests performed in a custom-made bioreactor. In the
      loading experiment, specimens were subjected to sinusoidal loading with a
      magnitude of 15% strain at a frequency of 1 hertz for 4 hours per day.
      Experiments were conducted for 2 consecutive days. This study showed that cyclic
      compressive loading promoted gene expressions of Sox9, c-Jun, and both TGF-beta
      receptors and productions of their corresponding proteins, whereas those gene
      expressions exhibited different temporal expression patterns among genes and
      between 2 days of testing. The gene expression of c-Fos was detected only in the
      samples subjected to1-hour dynamic compressive loading. These findings suggest
      that the TGF-beta signal transduction and activities of AP-1 and Sox9 are
      involved in the early stage of BM-MSC chondrogenesis promoted by dynamic
      compressive loading.

PMID- 15955835
TI  - Variable reprogramming of the pluripotent stem cell marker Oct4 in mouse clones:
      distinct developmental potentials in different culture environments.
AB  - A prevailing view of cloning by somatic-cell nuclear transfer is that
      reprogramming of gene expression occurs during the first few hours after
      injection of the nucleus into an oocyte, that the process is stochastic, and that
      the type of reprogramming needed for cloning success is foreign and unlikely to
      be readily achieved in the ooplasm. Here, we present evidence that the release of
      reprogramming capacity is contingent on the culture environment of the clone
      while the contribution of aneuploidy to altered gene expression is marginal. In
      particular, the rate of blastocyst formation in clones and the regional
      distribution of mRNA for the pluripotent stem cell marker Oct4 in clonal
      blastocysts was highly dependent on the culture environment after cumulus cell
      nuclear transfer, unlike that in genetically equivalent zygotes. Epigenetic
      modifications of genetically identical somatic nuclei continue after the first
      cell division of the clones and are amenable to a degree of experimental control,
      and their development to the blastocyst stage and appropriate expression of Oct4
      predict further outcome, such as derivation of embryonic stem (ES) cells, but not
      fetal development. This observation indicates that development to the blastocyst
      stage is not equivalent to full reprogramming and lends support to the novel
      concept that ES cells are not the equivalent of the inner cell mass, hence the
      discrepancy between ES cell derivability and fetal development of clones.

PMID- 15955836
TI  - Importance of integrin LFA-1 deactivation for the generation of immune responses.
AB  - The dynamic regulation of ligand binding is considered crucial for integrin
      function. However, the importance of activity regulation for integrin function in
      vivo is largely unknown. Here, we have applied gene targeting to delete the GFFKR
      sequence of the lymphocyte function-associated antigen-1 (LFA-1) alpha(L) subunit
      cytoplasmic domain in mouse germline. Lymphocytes from Lfa-1(d/d) mutant mice
      showed constitutive activation of LFA-1-mediated cell adhesion and impaired de
      adhesion from intercellular adhesion molecule-1 that resulted in defective cell
      migration. In contrast, signaling through LFA-1 was not affected in Lfa-1(d/d)
      cells. T cell activation by superantigen-loaded and allogeneic APCs, cytotoxic T
      cell activity, T-dependent humoral immune responses, and neutrophil recruitment
      during aseptic peritonitis were impaired in Lfa-1(d/d) mice. Thus, deactivation
      of LFA-1 and disassembly of LFA-1-mediated cell contacts seem to be vital for the
      generation of normal immune responses.

PMID- 15955837
TI  - Leukotriene B4, an activation product of mast cells, is a chemoattractant for
      their progenitors.
AB  - Mast cells are tissue-resident cells with important functions in allergy and
      inflammation. Pluripotential hematopoietic stem cells in the bone marrow give
      rise to committed mast cell progenitors that transit via the blood to tissues
      throughout the body, where they mature. Knowledge is limited about the factors
      that release mast cell progenitors from the bone marrow or recruit them to remote
      tissues. Mouse femoral bone marrow cells were cultured with IL-3 for 2 wk and a
      range of chemotactic agents were tested on the c-kit(+) population. Cells were
      remarkably refractory and no chemotaxis was induced by any chemokines tested.
      However, supernatants from activated mature mast cells induced pronounced
      chemotaxis, with the active principle identified as leukotriene (LT) B(4). Other
      activation products were inactive. LTB(4) was highly chemotactic for 2-wk-old
      cells, but not mature cells, correlating with a loss of mRNA for the LTB(4)
      receptor, BLT1. Immature cells also accumulated in vivo in response to
      intradermally injected LTB(4). Furthermore, LTB(4) was highly potent in
      attracting mast cell progenitors from freshly isolated bone marrow cell
      suspensions. Finally, LTB(4) was a potent chemoattractant for human cord blood
      derived immature, but not mature, mast cells. These results suggest an autocrine
      role for LTB(4) in regulating tissue mast cell numbers.

PMID- 15955838
TI  - Shifts in targeting of class switch recombination sites in mice that lack mu
      switch region tandem repeats or Msh2.
AB  - The mechanisms that target class switch recombination (CSR) to antibody gene
      switch (S) regions are unknown. Analyses of switch site locations in wild-type
      mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4
      5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for
      switching independent of Smu sequences. This CSR-accessible domain is reminiscent
      of the promoter-defined domains that target somatic hypermutation. Within the 4-5
      kb CSR domain, the targeting of S site locations also depends on the Msh2
      mismatch repair protein because Msh2-deficient mice show an increased focus of
      sites to the Smu tandem repeat region. We propose that Msh2 affects S site
      location because sequences with few activation-induced cytidine deaminase targets
      generate mostly switch DNA cleavages that require Msh2-directed processing to
      allow CSR joining.

PMID- 15955839
TI  - Properties and protective value of the secondary versus primary T helper type 1
      response to airborne Mycobacterium tuberculosis infection in mice.
AB  - Mice immunized against Mycobacterium tuberculosis (Mtb) infection by curing them
      of a primary lung infection were compared with naive mice in terms of the ability
      to generate a Th1 cell immune response and to control growth of an airborne Mtb
      challenge infection. Immunized mice generated and expressed Th1 cell immunity
      several days sooner than naive mice, as demonstrated by an earlier increase in
      the synthesis in the lungs of mRNA for Th1 cytokines and for inducible nitric
      oxide synthase, an indicator of macrophage activation. This Th1 cytokine/mRNA
      synthesis was accompanied by an earlier accumulation of Mtb-specific Th1 cells in
      the lungs and the presence of CD4 T cells in lesions. An earlier generation of
      immunity was associated with an earlier inhibition of Mtb growth when infection
      was at a 1-log lower level. However, inhibition of Mtb growth in immunized, as
      well as in naive, mice was not followed by resolution of the infection, but by
      stabilization of the infection at a stationary level. The results indicate that
      there is no reason to believe that the secondary response to an Mtb infection is
      quantitatively or qualitatively superior to the primary response.

PMID- 15955841
TI  - Long-term caloric restriction abrogates the age-related decline in skeletal
      muscle aerobic function.
AB  - The purpose of this study was to determine the effect of long-term caloric
      restriction (CR) on the age-associated decline of skeletal muscle aerobic
      function. Skeletal muscle maximal aerobic performance (VO2max) was assessed in ad
      libitum (AL) and CR rats aged 8-10 months and 35 months using a pump-perfused
      hindlimb model to match oxygen delivery to muscle mass between groups. Whereas
      there was a 46% decline in muscle mass-specific VO2max between 8-10 mo (524+/-13
      micromol x min(-1) x 100 g(-1); mean+/- SE) and 35 mo (281+/-54 micromol x min(
      1) x 100 g(-1)) in AL rats, not only did CR rats begin at the same point in 8-10
      mo old rats (490+/-42 micromol x min(-1) x 100 g(-1)), we found no decline in 35
      mo old CR animals (484+/-49 micromol x min(-1) x 100 g(-1)). Interestingly,
      although most markers of oxidative capacity began at a lower point in young adult
      CR animals, CR rats exhibited a higher in situ activity of complex IV at VO2max.
      This activity allows the young adult CR animals to exhibit normal aerobic
      capacity despite the lower oxidative enzyme activities. In stark contrast to the
      19-41% decline in activities of citrate synthase, complexes I-III, and complex IV
      in homogenates prepared from the plantaris muscle and mixed region of
      gastrocnemius muscle with aging in AL rats, no age-related decline was found in
      CR animals. Thus, our results showed that CR preserves aerobic function in aged
      skeletal muscles by facilitating a higher in situ function of complex IV and by
      preventing the age-related decline in mitochondrial oxidative capacity.

PMID- 15955840
TI  - Identification of eosinophil lineage-committed progenitors in the murine bone
      marrow.
AB  - Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in
      the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors
      (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the
      single cell level. Within the short-term culture of GMPs, the eosinophil
      potential was found exclusively in cells activating the transgenic reporter for
      GATA-1, a transcription factor capable of instructing eosinophil lineage
      commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c
      Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c
      Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly
      increased in number in response to helminth infection, suggesting that the EoP
      stage is physiologically involved in eosinophil production in vivo. EoPs
      expressed eosinophil-related genes, such as the eosinophil peroxidase and the
      major basic protein, but did not express basophil/mast cell-related mast cell
      proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not
      enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs
      displayed normal neutrophil/monocyte differentiation in the presence of IL-5
      alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a
      result of commitment into the eosinophil lineage. The newly identified EoPs could
      be the cellular target in the treatment of a variety of disorders mediated by
      eosinophils.

PMID- 15955842
TI  - Chemoattractant induces LFA-1 associated PI 3K activity and cell migration that
      are dependent on Fyn signaling.
AB  - The activation state of integrins on leukocytes is tightly controlled by the
      association of intracellular molecules to the cytoplasmic domain of the integrin.
      To identify signaling intermediates involved in chemoattractant receptor-induced
      integrin activation, we analyzed the ability of LFA-1 integrin to associate with
      members of Src tyrosine kinase and phosphatidylinositol 3Kinase (PI 3K) families
      following fMLP stimulation of a lymphoid T cell line stably expressing the fMLP
      receptor (fPR). fMLP-induced cell activation resulted in a rapid increase of
      integrin-associated PI 3Kinase activity in G protein and Src kinase dependent
      manner. We show, upon fMLP-stimulation, a rapid and transient association of the
      Src tyrosine kinase Fyn with LFA-1. Also, by transiently expressing mutant forms
      of this kinase, we demonstrated that Fyn is required for the integrin associated
      PI 3K activity. Furthermore, overexpression of the mutant form of Fyn resulted in
      a significant impairment of fMLP-induced cell migration through ICAM-1-coated
      filters, while ICAM-1 independent migration was not affected. Our observations
      indicate that chemoattractant receptor engagement induces Fyn-dependent PI 3K
      activation in association with LFA-1 and suggests that Fyn is necessary to
      initiate and/or to regulate chemoattractant-mediated LFA-1 activation to promote
      directional migration.

PMID- 15955843
TI  - Effects of RNA degradation on gene expression analysis of human postmortem
      tissues.
AB  - The Affymetrix GeneChip platform was used to build a gene expression database of
      the normal human body. Postmortem human tissues represent a valuable source of
      biological materials for this type of study, but their use entails some delays
      before harvesting such tissues. We first evaluated the RNA quality obtained from
      tissues obtained 3-5 h postmortem and found variations that were both tissue and
      donor-dependent. RNAs extracted from brain regions were of higher quality than
      those obtained from the gut, while the cause of death was a significant factor in
      donor-dependent differences. To avoid these variables, we used rat duodenum to
      determine the effects of RNA degradation on the analysis of gene expression.
      Surprisingly, even samples exhibiting significant RNA degradation yielded robust
      gene expression results, comparable to those obtained using intact samples at a
      certain signal intensity cutoff. We extended these findings to our human
      expression database and obtained similar results, indicating that the Affymetrix
      platform, which is biased to the 3' end of transcripts for detection, can
      tolerate significant RNA degradation, while still yielding high quality
      expression data. Our resulting body index expression database is a valuable
      research tool. As examples of potential uses, we report novel expression sites
      for four potential therapeutic targets--CCL27, GPR22, GPR113 and GPR128--and as
      well as a set of thymus-specific genes, including three not previously associated
      with the thymus.

PMID- 15955844
TI  - Leptin pulsatility in formerly obese women.
AB  - Plasma leptin and growth hormone (GH) profile and pulsatility have been studied
      in morbidly obese subjects before and 14 months after bilio-pancreatic diversion
      (BPD), a bariatric technique producing massive lipid malabsorption. The maximum
      leptin diurnal variation (acrophase) decreased (10.27+/-1.70 vs. 22.60+/-2.79 ng
      x ml(-1); P=0.001), while its pulsatility index (PI) increased (1.084+/-0.005 vs.
      1.050+/-0.004 ng x ml(-1) x min(-1); P=0.02) after BPD. Plasma GH acrophase
      increased (P=0.0001) from 0.91+/-0.20 to 4.58+/-0.80 microg x l(-1) x min(-1)
      after BPD as well as GH PI (1.70+/-0.13 vs. 1.20+/-0.04 microg x l(-1) x min(-1);
      P=0.024). Whole-body glucose uptake (M), assessed by euglycemic-hyperinsulinemic
      clamp, almost doubled after BPD (from 0.274+/-0.022 to 0.573+/-0.027 mmol x
      kgFFM(-1) x min(-1); P<0.0001), while 24 h lipid oxidation was significantly
      (P<0.0001) reduced (131.94+/-35.58 vs. 44.56+/-15.10 g). However, the average
      lipid oxidation was 97.2+/-3.1% (P<0.01) of the metabolizable lipid intake after
      the bariatric operation, while it was 69.2+/-8.5% before. After the operation,
      skeletal muscle ACC2 mRNA decreased (P<0.0001) from 452.82+/-76.35 to 182.45+/
      40.69% of cyclophilin mRNA as did the malonyl-CoA (from 0.28+/-0.02 to 0.16+/
      0.01 nmol x g(-1); P<0.0001). Leptin changes negatively correlated with M changes
      (R2=0.69, P<0.001). In a stepwise regression (R2=0.87, P=0.0055), only changes in
      24 h free fatty acids (B=0.105+/-0.018, P=0.002) and glucose/insulin ratio
      (B=0.247+/-0.081, P=0.029) were the best predictors of leptin variations. In
      conclusion, the reversion of insulin resistance after BPD might allow reversal of
      leptin resistance, restoration of leptin pulsatility, and consequent inhibition
      of ACC2 mRNA expression, translating to a reduced synthesis of malonyl-CoA,
      which, in turn, results in increased fatty acid oxidation. Finally, since leptin
      inhibits GH secretion, a reduction of circulating leptin levels might have
      produced an increase in GH secretion, as observed in our series.

PMID- 15955845
TI  - G protein beta interacts with the glucocorticoid receptor and suppresses its
      transcriptional activity in the nucleus.
AB  - Extracellular stimuli that activate cell surface receptors modulate
      glucocorticoid actions via as yet unclear mechanisms. Here, we report that the
      guanine nucleotide-binding protein (G protein)-coupled receptor-activated WD
      repeat Gbeta interacts with the glucocorticoid receptor (GR), comigrates with it
      into the nucleus and suppresses GR-induced transactivation of the glucocorticoid
      responsive genes. Association of Ggamma with Gbeta is necessary for this action
      of Gbeta. Both endogenous and enhanced green fluorescent protein (EGFP)-fused
      Gbeta2 and Ggamma2 proteins were detected in the nucleus at baseline, whereas a
      fraction of EGFP-Gbeta2 and DsRed2-GR comigrated to the nucleus or the plasma
      membrane, depending on the exposure of cells to dexamethasone or somatostatin,
      respectively. Gbeta2 was associated with GR/glucocorticoid response elements
      (GREs) in vivo and suppressed activation function-2-directed transcriptional
      activity of the GR. We conclude that the Gbetagamma complex interacts with the GR
      and suppresses its transcriptional activity by associating with the
      transcriptional complex formed on GR-responsive promoters.

PMID- 15955846
TI  - The exocyst component Sec5 is present on endocytic vesicles in the oocyte of
      Drosophila melanogaster.
AB  - The exocyst is an octameric complex required for polarized secretion. Some
      components of the exocyst are found on the plasma membrane, whereas others are
      recruited to Golgi membranes, suggesting that exocyst assembly tethers vesicles
      to their site of fusion. We have found that in Drosophila melanogaster oocytes
      the majority of the exocyst component Sec5 is unexpectedly present in clathrin
      coated pits and vesicles at the plasma membrane. In oocytes, the major substrate
      for clathrin-dependent endocytosis is the vitellogenin receptor Yolkless. A
      truncation mutant of Sec5 (sec5(E13)) allows the formation of normally sized
      oocytes but with greatly reduced yolk uptake. We find that in sec5(E13) oocytes
      Yolkless accumulates aberrantly in late endocytic compartments, indicating a
      defect in the endocytic cycling of the receptor. An analogous truncation of the
      yeast SEC5 gene results in normal secretion but a temperature-sensitive defect in
      endocytic recycling. Thus, the exocyst may act in both Golgi to plasma membrane
      traffic and endocytic cycling, and hence in oocytes is recruited to clathrin
      coated pits to facilitate the rapid recycling of Yolkless.

PMID- 15955847
TI  - Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3beta in
      migrating epithelial cells.
AB  - Proteins that in cells specifically bind to growing microtubule plus ends (+TIPs)
      are thought to play important roles in polarization of the cytoskeleton. However,
      most +TIPs do not show a bias of their microtubule-binding behavior toward
      different subcellular regions. Here, we examine the dynamics of the +TIP CLASP in
      migrating PtK1 epithelial cells. We find that, although CLASPs track microtubule
      plus ends in the cell body, they dynamically decorate the entire microtubule
      lattice in the leading edge lamella and lamellipodium. Microtubule lattice
      binding is mediated by the COOH-terminal region of the CLASP microtubule-binding
      domain and is regulated downstream of Rac1. Phosphorylation of sites in the NH2
      terminal part of the microtubule-binding domain by glycogen synthase kinase 3beta
      likely regulates the affinity of CLASPs for microtubule lattices. These results
      demonstrate the striking difference of the microtubule cytoskeleton in the
      lamella as compared with the cell body and provide the first direct observation
      of subcellular regulation of a microtubule-associated protein in migrating cells.

PMID- 15955848
TI  - A positive feedback loop between Dumbfounded and Rolling pebbles leads to myotube
      enlargement in Drosophila.
AB  - In Drosophila, myoblasts are subdivided into founders and fusion-competent
      myoblasts (fcm) with myotubes forming through fusion of one founder and several
      fcm. Duf and rolling pebbles 7 (Rols7; also known as antisocial) are expressed in
      founders, whereas sticks and stones (SNS) is present in fcm. Duf attracts fcm
      toward founders and also causes translocation of Rols7 from the cytoplasm to the
      fusion site. We show that Duf is a type 1 transmembrane protein that induces
      Rols7 translocation specifically when present intact and engaged in homophilic or
      Duf-SNS adhesion. Although its membrane-anchored extracellular domain functions
      as an attractant and is sufficient for the initial round of fusion, subsequent
      fusions require replenishment of Duf through cotranslocation with Rols7
      tetratricopeptide repeat/coiled-coil domain-containing vesicles to the
      founder/myotube surface, causing both Duf and Rols7 to be at fusion sites between
      founders/myotubes and fcm. This implicates the Duf-Rols7 positive feedback loop
      to the occurrence of fusion at specific sites along the membrane and provides a
      mechanism by which the rate of fusion is controlled.

PMID- 15955850
TI  - Effect of endocardial trabeculae on left ventricular measurements and measurement
      reproducibility at cardiovascular MR imaging.
AB  - PURPOSE: To prospectively assess the effect of including or excluding endocardial
      trabeculae in left ventricular (LV) measurements and the reproducibility of these
      measurements at cine cardiovascular magnetic resonance (MR) imaging with true
      fast imaging with steady-state precession (FISP). MATERIALS AND METHODS: The
      study was approved by the local ethics committee, and each subject gave informed
      consent before participating. Twenty healthy subjects and 20 consecutive patients
      underwent 1.5-T cardiovascular MR imaging. Seven to 12 short-axis views
      encompassing the entire LV were acquired by using true FISP. Endocardial and
      epicardial contours were traced manually. The data sets in each patient were
      analyzed twice: with inclusion of endocardial trabeculae in the LV cavity volume
      and with exclusion of endocardial trabeculae from the cavity volume. On the basis
      of these two contour sets, the end-diastolic (ED) and end-systolic (ES) LV
      volumes, ejection fraction (EF), and LV mass were calculated. Additionally,
      interobserver and interexamination reproducibility was assessed by using Bland
      Altman analysis. RESULTS: Compared with exclusion of trabeculae, inclusion of
      trabeculae in the LV cavity volume resulted in significantly larger ED and ES LV
      volumes (mean differences, 21 mL +/- 11 [standard deviation] and 19 mL +/- 33,
      respectively; P < .001) and lower EFs (mean difference, -2% +/- 2; P < .001). The
      calculated LV mass was significantly smaller with inclusion than with exclusion
      of trabeculae (mean difference, -21 g +/- 12; P < .001). All interobserver and
      interexamination limits of agreement based on inclusion of trabeculae, except
      those for EF measurements, were superior to those based on exclusion of
      trabeculae. At measurement reproducibility comparisons, differences in
      interobserver ED LV volume and LV mass and interexamination LV mass were
      statistically significant, favoring the inclusion of trabeculae in the LV cavity
      volume. CONCLUSION: Trabeculae significantly affect quantifications of LV volume
      and mass. The superior reproducibility of LV measurements with the inclusion of
      endocardial trabeculae in the cavity volume favors this tracing algorithm for
      clinical use.

PMID- 15955849
TI  - Unzipped and loaded: the role of DNA helicases and RFC clamp-loading complexes in
      sister chromatid cohesion.
AB  - It is well known that the products of chromosome replication are paired to ensure
      that the sisters segregate away from each other during mitosis. A key issue is
      how cells pair sister chromatids but preclude the catastrophic pairing of
      nonsister chromatids. The identification of both replication factor C and DNA
      helicases as critical for sister chromatid pairing has brought new insights into
      this fundamental process.

PMID- 15955851
TI  - True versus false left ventricular aneurysm: differentiation with MR imaging-
      initial experience.
AB  - PURPOSE: To assess the usefulness of cardiac magnetic resonance (MR) imaging for
      differentiation of true from false left ventricular aneurysm in patients after
      myocardial infarction. MATERIALS AND METHODS: Cardiac MR images obtained in 22
      sequential patients (20 men, two women; mean age, 63 years; age range, 45-75
      years) with pathologically proved left ventricular true aneurysm (n = 18) or
      false aneurysm (n = 4) after myocardial infarction were retrospectively analyzed.
      The MR imaging protocol included steady-state cine imaging followed by perfusion
      measurement and delayed contrast-enhanced imaging with delays of 15 and 20
      minutes. Differences between true and false aneurysms with regard to maximal
      internal width of orifice, maximal parallel internal diameter, ratio of maximal
      orifice to maximal internal diameter, presence of mural thrombus and delayed
      enhancement of pericardium, left ventricular end-diastolic volume, and left
      ventricular ejection fraction were analyzed by using the Mann-Whitney U test or
      Fisher exact test, as appropriate. RESULTS: Inferior wall location was noted in
      two of four patients with false aneurysm and in none of 18 patients with true
      aneurysm (P = .03). The remaining aneurysms were apicoanterior (two false, 10
      true) or apical (eight true). False aneurysms had a ratio of maximal internal
      width of the orifice to maximal parallel internal diameter that was significantly
      lower than that of true aneurysms (0.73 vs 1.00, P < .001) and had a
      significantly higher left ventricular end-diastolic volume (median, 202 vs 136
      mL/m(2); P = .001), as well as a nonsignificant tendency toward lower left
      ventricular ejection fraction (17% vs 28%, P = .15). Mural thrombus was
      identified in all four patients with false aneurysm and in seven of 18 patients
      with true aneurysm (P = .09). Delayed enhancement of pericardium was noted in all
      four patients with false aneurysm and in three of 18 patients with true aneurysm.
      Resultant sensitivity of MR imaging for the detection of false left ventricular
      aneurysm was four of four, specificity was 15 of 18, accuracy was 19 of 22, and
      positive and negative predictive values were four of seven and 15 of 15 patients,
      respectively. CONCLUSION: Initial experience with a small number of patients
      suggests that marked delayed enhancement of the pericardium is a characteristic
      feature of false aneurysm. Study with a larger patient sample is required to
      further assess this feature.

PMID- 15955852
TI  - Pulmonary candidiasis after hematopoietic stem cell transplantation: thin-section
      CT findings.
AB  - PURPOSE: To retrospectively evaluate thin-section computed tomographic (CT)
      findings in hematopoietic stem cell transplant (ie, bone marrow transplant)
      patients with histopathologically proved pulmonary candidiasis. MATERIALS AND
      METHODS: Ethical approval was obtained from the institutional review board of
      each of the three institutions; informed consent was not required. The study
      included 17 hematopoietic stem cell transplant recipients with proved pulmonary
      candidiasis. Histopathologic specimens were acquired at transbronchial biopsy (n
      = 8), open lung biopsy (n = 6), and autopsy (n = 3). The patients included seven
      men and 10 women (age range, 20-62 years; mean age, 37 years). The thin-section
      CT scans were retrospectively reviewed by two thoracic radiologists for the
      presence, appearance, and distribution of parenchymal abnormalities. RESULTS:
      Multiple nodules were present in 15 (88%) patients, including centrilobular
      nodules and tree-in-bud pattern in seven (41%) patients. Nodules were bilateral
      in 12 patients and unilateral in three. An associated halo of ground-glass
      opacity was identified in five (33%) patients. Nodules were the only CT finding
      in five patients (29%). Areas of air-space consolidation were identified in 11
      (65%) patients. Areas of ground-glass opacity were seen in six (35%) of 17
      patients and were always associated with other abnormalities. Other less common
      CT findings included pleural effusion (n = 3), thickening of the bronchial walls
      (n = 2), and cavitation (n = 1). CONCLUSION: The most common thin-section CT
      findings of pulmonary candidiasis in hematopoietic stem cell transplant patients
      are multiple bilateral nodular opacities often associated with areas of
      consolidation.

PMID- 15955853
TI  - Carotid artery stenosis: intraindividual correlations of 3D time-of-flight MR
      angiography, contrast-enhanced MR angiography, conventional DSA, and rotational
      angiography for detection and grading.
AB  - PURPOSE: To compare three-dimensional (3D) time-of-flight (TOF) MR angiography,
      contrast-enhanced MR angiography, digital subtraction angiography (DSA), and
      rotational angiography for depiction of stenosis. MATERIALS AND METHODS: The
      study had Ethics Committee approval, and each patient gave written informed
      consent. Forty-nine patients (18 women, mean age, 67.2 years +/- 9.1 [+/-
      standard deviation], and 31 men, mean age, 63.1 years +/- 8.0) with symptomatic
      stenosis of internal carotid artery (ICA) diagnosed at duplex ultrasonography
      underwent transverse 3D TOF MR angiography with sliding interleaved kY
      acquisition and coronal contrast-enhanced MR angiography, followed by DSA and
      rotational angiography within 48 hours. MR angiography was performed at 1.5-T
      with a cervical coil. Contrast-enhanced MR angiograms were obtained after a bolus
      injection of 20 mL of gadobenate dimeglumine. Maximum ICA stenosis on maximum
      intensity projection and source images was quantified according to NASCET
      criteria. Correlations for 3D TOF MR angiography, contrast-enhanced MR
      angiography, DSA, and rotational angiography were determined by means of cross
      tabulation, and accuracy for detection and grading of stenoses were calculated.
      Data were evaluated with analysis of variance, Wilcoxon signed rank test, and
      McNemar test, all at significance of P < .05. RESULTS: Ninety-eight ICAs were
      evaluated at contrast-enhanced MR angiography, DSA, and rotational angiography,
      and 97 were evaluated at 3D TOF MR angiography. Correlations for contrast
      enhanced MR angiography, 3D TOF MR angiography, and DSA relative to rotational
      angiography were r2 = 0.9332, r2 = 0.9048, and r2 = 0.9255, respectively. Lower
      correlation (r2 = 0.8593) was noted for contrast-enhanced MR angiography and DSA.
      Respective sensitivity and specificity for detection of hemodynamically relevant
      stenosis relative to rotational angiography were 100% and 90% for contrast
      enhanced MR angiography, 95.5% and 87.2% for 3D TOF MR angiography, and 88.6% and
      100% for DSA. Four of 31 severe stenoses were underestimated at DSA, and three
      were underestimated at contrast-enhanced MR angiography. Three severe stenoses
      were underestimated at 3D TOF MR angiography, and one was misclassified as
      occluded. Of 13 moderate (50%-69%) stenoses, one was overestimated at contrast
      enhanced MR angiography, two were underestimated and three overestimated at 3D
      TOF MR angiography, and two were underestimated at DSA. CONCLUSION: DSA results
      in an underestimation of ICA stenosis compared with rotational angiography.
      Contrast-enhanced MR angiography correlates best with rotational angiography.

PMID- 15955854
TI  - Endovascular brachytherapy: restenosis in de novo versus recurrent lesions of
      femoropopliteal artery--the Vienna experience.
AB  - PURPOSE: To determine the effectiveness of endovascular brachytherapy in the
      prevention of restenosis in recurrent versus de novo femoropopliteal lesions.
      MATERIALS AND METHODS: Ethics committee approval and patient informed consent
      were obtained. After they had undergone femoropopliteal angioplasty, 199 patients
      (mean age, 71.9 years +/- 9.6; 115 men, 84 women) were treated with either
      percutaneous transluminal angioplasty (PTA) and brachytherapy (n = 100) or PTA
      alone (n = 99). The patients were part of prospective randomized trials, the
      Vienna 2 and 3 trials, and were evaluated according to the stratification
      criterion of de novo or recurrent disease. Sixty-six of 134 patients with a de
      novo lesion and 34 of 65 patients with a recurrent lesion were randomly assigned
      to the PTA and brachytherapy arm; the remaining patients were treated with PTA
      alone. Outcomes were compared between the groups. The Student t test or one-way
      analysis of variance was used to compare continuous variables, and the chi2 test
      or Fisher exact test was used to assess dichotomous variables. Kaplan-Meier
      curves were calculated, and the log-rank test was performed to determine freedom
      from recurrence at 12 months in both groups. A multivariate Cox proportional
      hazard regression analysis was performed to evaluate the multivariate predictors
      of recurrence at 12-month follow-up. RESULTS: For patients with de novo lesions,
      the frequency of recurrence at 12 months was not significantly different between
      those who underwent brachytherapy and PTA and those who underwent PTA alone (24
      [36%] of 66 patients vs 30 [44%] of 68 patients, P = .32). For patients with
      recurrent lesions, however, the 12-month recurrence rate was significantly lower
      in those who received brachytherapy than in those who did not (nine [26%] of 34
      patients vs 22 [71%] of 31 patients, P = .004). CONCLUSION: Endovascular
      brachytherapy with gamma radiation significantly reduces the restenosis rate
      after femoropopliteal angioplasty of recurrent but not de novo lesions.

PMID- 15955855
TI  - Hydronephrotic kidney: pediatric three-dimensional US for relative renal size
      assessment--initial experience.
AB  - PURPOSE: To prospectively evaluate accuracy of three-dimensional (3D)
      ultrasonography (US) for assessment of relative renal size in infants and
      children with hydronephrosis. MATERIALS AND METHODS: Informed consent was
      obtained from parents and also from children who were older than 8 years. Study
      was approved by ethics committee. Two-dimensional (2D) US, 3D US, and
      scintigraphy were performed in 40 patients with hydronephrosis (age range,
      neonate to 16 years; seven girls, 33 boys) without acute renal disease. Twenty
      patients also underwent magnetic resonance (MR) urography. US and MR urography
      were performed by one experienced pediatric radiologist; 3D US and MR urographic
      volume calculations were performed by specifically trained radiologists. Three
      dimensional US was performed with integrated 3D volume probes or external system
      based on electromagnetic positioning devices. At 2D US, kidney volume was
      calculated with application of ellipsoid equation. At MR urography and 3D US,
      real renal parenchymal volume was calculated with subtraction of dilated
      collecting system. Split renal function was assessed with static renal
      scintigraphy. Three-dimensional US results were graded with respect to image
      quality and compared with results of 2D US, scintigraphy, and MR urography by
      using mean difference percentage and standard deviation of the difference. All
      investigations were performed with blinding. Inter- and intraobserver variability
      were calculated with coefficient of variation. RESULTS: In 76 of 80 kidneys, 3D
      US image of diagnostic quality was obtained. Three-dimensional US volume
      measurements compared well with MR urographic measurements (mean difference, 
      2.5% +/- 7.8 [standard deviation] vs 25.8% +/- 32.2 for 2D US) and with
      scintigraphically assessed split renal function (mean difference, 1.2% +/- 9.2 vs
      15.9% +/- 43.8 for 2D US). Intra- and interobserver variability were +/-6.4% and
      +/-9.9%, respectively. CONCLUSION: Initial experience with renal 3D US indicates
      that it is an accurate method for assessment of renal parenchymal volume and
      relative renal size, provided there is no acute renal disease.

PMID- 15955856
TI  - Treatment of hepatic venous outflow obstruction after piggyback liver
      transplantation.
AB  - PURPOSE: To evaluate retrospectively the endovascular management of hepatic
      venous outflow obstruction after piggyback orthotopic liver transplantation.
      MATERIALS AND METHODS: The study was performed with the approval and under the
      guidelines of the institutional review board and complied with the Health
      Insurance Portability and Accountability Act. Informed consent from patients was
      not required by the institutional review board for this retrospective study. From
      1995 to 2003, 13 patients (eight male, five female), including 12 adults and one
      adolescent (age range, 14-67 years; median age, 52 years), underwent endovascular
      treatment of hepatic venous outflow obstruction after piggyback orthotopic liver
      transplantation. Patients gave informed consent for all procedures. Eleven
      patients received whole livers, and two received living-related donor right liver
      lobes. Four underwent repeat piggyback orthotopic liver transplantation prior to
      intervention. Primary stent placement was performed in 12 patients. One patient
      refused primary stent placement and chose venoplasty alone, but required a stent
      5 months later. Short balloon-expandable stents (mean diameter, 14.6 mm +/- 1.1
      [standard deviation]) were used to minimize jailing of branch vessels and to
      resist recoil. Pre- and post-procedural pressure gradients were measured. Follow
      up included venography, cross-sectional imaging, and laboratory tests. The
      Wilcoxon signed rank test or the sign test was performed to compare pre- and post
      procedural pressure gradients, body weights, and laboratory values. RESULTS:
      Technical success (pressure gradient < or = 3 mm Hg) was achieved in 13 of 13
      patients, and clinical success, in 12 of 13. Mean pre- and post-procedural
      pressure gradients were 13.0 mm Hg +/- 1.4 and 0.8 mm Hg +/- 0.3. Mean interval
      from transplantation to intervention was 348 days +/- 159. Mean follow-up was 678
      days (range, 16-2880 days). Technical success did not result in clinical
      improvement in one patient. Biopsy demonstrated severe hepatic necrosis, likely
      from prolonged venous congestion, and the patient required repeat
      transplantation. Only one patient required reintervention for stent migration,
      and no other complications occurred. No significant restenosis was encountered
      after stent placement. CONCLUSION: Hepatic venous outflow obstruction is an
      uncommon but potentially fatal complication of piggyback orthotopic liver
      transplantation. Endovascular treatment with balloon-expandable stents is
      effective, safe, and apparently durable.

PMID- 15955857
TI  - Accurate differentiation of focal nodular hyperplasia from hepatic adenoma at
      gadobenate dimeglumine-enhanced MR imaging: prospective study.
AB  - PURPOSE: To prospectively determine the accuracy of differentiating benign focal
      nodular hyperplasia (FNH) from hepatic adenoma (HA) and liver adenomatosis (LA)
      by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging.
      MATERIALS AND METHODS: The ethics committee at each center approved the study,
      and all patients provided informed consent. Seventy-three patients with confirmed
      FNH and 35 patients with confirmed HA (n = 27) or LA (n = 8) underwent MR imaging
      before (T2-weighted half-Fourier rapid acquisition with relaxation enhancement or
      T2-weighted fast spin-echo and T1-weighted gradient-echo [GRE] sequences) and at
      25-30 seconds (arterial phase), 70-90 seconds (portal venous phase), 3-5 minutes
      (equilibrium phase), and 1-3 hours (delayed phase) after (T1-weighted GRE
      sequences only, with or without fat suppression) bolus administration of 0.1 mmol
      per kilogram of body weight gadobenate dimeglumine. The enhancement of 235
      lesions (128 FNH, 32 HA, and 75 LA lesions) relative to the normal liver
      parenchyma was assessed. Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), and overall accuracy for the
      differentiation of FNH from HA and LA were determined. RESULTS: Hyper- and
      isointensity on T2-weighted and iso- and hypointensity on T1-weighted GRE images
      were noted for 177 (88.9%) of 199 lesions visible on unenhanced images. On
      dynamic phase images after contrast material administration, 231 (98.3%) of 235
      lesions showed rapid strong enhancement during the arterial phase and appeared
      hyper- to isointense during portal venous and equilibrium phases. Accurate
      differentiation of FNH from HA and LA was not possible on the basis of
      precontrast or dynamic phase images alone. At 1-3 hours after contrast material
      enhancement, 124 (96.9%) of 128 FNHs appeared hyper- or isointense, while 107
      (100%) HA and LA lesions appeared hypointense. The sensitivity, specificity, PPV,
      NPV, and overall accuracy for the differentiation of FNH from HA and LA were
      96.9%, 100%, 100%, 96.4%, and 98.3%, respectively. CONCLUSION: Accurate
      differentiation of FNH from HA and LA is achievable on delayed T1-weighted GRE
      images after administration of gadobenate dimeglumine.

PMID- 15955858
TI  - Transjugular intrahepatic portosystemic shunts: adjunctive embolotherapy of
      gastroesophageal collateral vessels in the prevention of variceal rebleeding.
AB  - PURPOSE: To prospectively compare rebleeding rates in patients treated with
      transjugular intrahepatic portosystemic shunt (TIPS) creation alone and those
      treated with TIPS creation combined with adjunctive embolotherapy of
      gastroesophageal collateral vessels. MATERIALS AND METHODS: Informed consent and
      ethics committee approval were obtained. Between November 1991 and November 2002,
      the authors prospectively followed up 95 consecutive patients (61 men, 34 women;
      age range, 30-81 years) with variceal bleeding due to cirrhosis and portal
      hypertension. The patients were divided into two groups on the basis of
      splenoportographic findings after TIPS creation. The patients were treated with
      TIPS alone (group 1, 42 patients) or in combination with variceal embolotherapy
      (group 2, 53 patients). Embolotherapy with sclerosing agents in combination with
      coils was performed when varices continued to fill and the pressure gradient was
      more than 12 mm Hg. Rebleeding was defined as any hemorrhage necessitating a
      transfusion of 2 or more units of blood. Estimates for the cumulative patency,
      survival, and rebleeding rates were calculated by using life-table analysis; the
      log-rank test was used to compare the two treatment modalities. The prognostic
      relevance of treatment and selected variables with respect to rebleeding and
      survival were analyzed with multiple logistic regression. RESULTS: Mean follow-up
      time (+/- standard deviation) was 48.7 months +/- 37.8 (range, 1-127 months). The
      proportion of patients (Kaplan-Meier estimation) with TIPS who remained free of
      bleeding was 61% after 2 years and 53% after 4 years. Patients who underwent both
      the TIPS procedure and embolotherapy remained free of bleeding in 84% of cases
      after 2 years and in 81% of cases after 4 years. With respect to the rebleeding
      rate, the difference between the groups was statistically significant (log-rank
      test, P = .02). Results of multiple logistic regression analysis showed that
      variceal embolotherapy significantly reduced the risk of rebleeding (Wald test, P
      < .001). CONCLUSION: The results suggest that TIPS and adjunctive embolotherapy
      of gastroesophageal collateral vessels significantly lower the rebleeding rate in
      comparison to TIPS alone.

PMID- 15955859
TI  - Differentiating malignant from benign common bile duct stricture with multiphasic
      helical CT.
AB  - PURPOSE: To evaluate retrospectively the use of multiphasic helical computed
      tomography (CT) to differentiate malignant and benign common bile duct (CBD)
      strictures in patients with only a focal CBD stricture and to determine
      predictors for this differentiation. MATERIALS AND METHODS: Institutional review
      board approval and informed patient consent were not required. Fifty patients (35
      men, 15 women; age range, 35-87 years; mean age, 61.6 years) with only a focal
      CBD stricture comprised the sample for this study (32 malignant and 18 benign
      strictures). The diagnosis of all malignant and five benign CBD strictures was
      confirmed by reviewing patients' surgical and pathology records; in 13 benign CBD
      strictures, the diagnosis was confirmed by means of clinical features.
      Multiphasic CT findings were analyzed with regard to the wall thickness,
      location, length, and enhancement pattern of the involved CBD, the upstream CBD
      diameter, and other findings. CT features to identify benign and malignant CBD
      strictures were compared by means of univariate analysis and multivariable
      stepwise logistic regression analysis. RESULTS: Malignant strictures were longer
      (17.9 mm +/- 6.6 [+/- standard deviation]) than benign strictures (8.9 mm +/-
      6.8) (P < .0001), and upstream CBD diameters were larger in malignant cases (22.0
      mm +/- 5.4) than in benign cases (17.8 mm +/- 4.6) (P = .033). The involved wall
      thickness was more than 1.5 mm in 26 malignant cases and three benign cases (P <
      .0001). During both hepatic arterial and portal venous phases, greater
      enhancement than that in the normal CBD were more frequently observed in
      malignant cases (in 27 and 30 patients for hepatic arterial and portal venous
      phase scans, respectively) than in benign cases (in two and three patients,
      respectively) (P < .0001). Results of multivariable stepwise logistic regression
      analysis showed that hyperenhancement of the involved CBD during the portal
      venous phase was the only variable that could be used to independently
      differentiate malignant from benign strictures. CONCLUSION: Hyperenhancement of
      the involved CBD during the portal venous phase is the main factor distinguishing
      malignant from benign CBD strictures.

PMID- 15955860
TI  - Identification of Staphylococcus aureus brain abscesses: rat and human studies
      with 1H MR spectroscopy.
AB  - PURPOSE: To determine the feasibility of a statistical classification strategy
      (SCS) and the identity of metabolites of bacterial and host origins that
      potentially contributed to the most discriminatory regions of magnetic resonance
      (MR) spectra from Staphylococcus aureus abscesses of biopsy material from
      controls, gliomas, and staphylococcal abscesses. MATERIALS AND METHODS: Human and
      animal study received ethics committee approval, and informed patient consent was
      obtained. A rat model of S aureus brain abscess was developed. Histologic and
      microbiologic examination was performed to assess abscess development 3-4, 6-8,
      and 10-15 days after initiation. Metabolite profiles in pus (n = 62) and controls
      (n = 37) were characterized with ex vivo MR spectroscopy and compared with data
      from rat gliomas (n = 27). SCS, optimal region selection, and development of
      pairwise classifiers allowed MR spectra of abscesses (n = 42, day 6-8) to be
      distinguished from those of glioblastoma multiforme and controls. MR spectroscopy
      profiles of pus from animal abscesses were compared with in vivo MR spectra from
      patients with staphylococcal brain abscesses (n = 7, aged 6-67 years) and ex vivo
      pus MR spectra from patients with S aureus abscesses. RESULTS: Histologically
      confirmed abscesses were present 6-8 days after stereotactic injection of S
      aureus in 42 of 47 rats (89%). MR spectra of abscesses and glioblastoma
      multiforme in the animal model were similar. Typical metabolites of abscesses due
      to anaerobe bacteria (acetate, succinate, amino acids) were not detectable in S
      aureus abscesses in rats or humans. MR spectroscopic findings from controls,
      abscesses, and gliomas were distinguished by means of SCS with an accuracy of
      99%. Analysis of the most discriminatory regions with two-dimensional correlation
      spectra indicated that glutamine and/or glutamate and aspartate potentially
      contributed to successful classification. CONCLUSION: S aureus is detectable in
      abscesses with a non-culture-based method in an animal model.

PMID- 15955861
TI  - Acute myocardial infarction: assessment of left ventricular function with 16
      detector row spiral CT versus MR imaging--study in pigs.
AB  - PURPOSE: To assess global left ventricular (LV) function and regional wall motion
      with retrospective electrocardiographically gated 16-detector row computed
      tomography (CT) in comparison with magnetic resonance (MR) imaging. MATERIALS AND
      METHODS: In 15 pigs (mean weight, 53.9 kg +/- 9.5 [standard deviation]), acute
      myocardial infarction was induced with balloon occlusion of the left anterior
      descending coronary artery after approval was obtained from the committee on
      animal affairs. Thereafter, multi-detector row CT and MR imaging were performed
      with standardized examination protocols. From manually drawn endocardial and
      epicardial contours, LV volumes, including mean ejection fraction, peak filling
      rate (PFR), peak ejection rate (PER), time to PER, and time from end systole to
      PFR, were calculated. Regional wall motion was assessed from cine loops with a 16
      segment model of the left ventricle. LV function was analyzed by using Bland
      Altman plots, Student t test, and Pearson correlation coefficient. Regional wall
      motion scores were compared with weighted kappa statistic. RESULTS: LV volumes
      determined with multi-detector row CT correlated well with MR imaging results,
      with an ejection fraction of 46.1% +/- 6.5 for multi-detector row CT and 46.8% +/
      5.9 for MR imaging (r = 0.97). PER, PFR, time to PER, and time from end systole
      to PFR showed a wide range of scattering and significant differences between
      multi-detector row CT and MR imaging for PER and time from end systole to PFR (P
      < .05). Regional wall motion scores showed a very high level of agreement with a
      kappa value of 0.88. CONCLUSION: Although 16-detector row CT allows reliable
      assessment of LV volumes and regional wall motion at rest, it is not suited for
      assessment of all functional parameters.

PMID- 15955862
TI  - Pulmonary nodules: automated detection on CT images with morphologic matching
      algorithm--preliminary results.
AB  - Institutional review board approval was obtained. Informed patient consent was
      not required for this retrospective study, which involved review of previously
      obtained image data. Patient confidentiality was protected; the study was
      compliant with the Health Insurance Portability and Accountability Act. An
      automated pulmonary nodule detection program that takes advantage of three
      dimensional volumetric data was developed and tested with multi-detector row
      computed tomographic (CT) images from 20 patients (13 men, seven women; age
      range, 40-75 years) with pulmonary nodules. A total of 164 nodules 3 mm in
      diameter and larger were detected by two radiologists in consensus and were used
      as a reference standard to evaluate the computer-aided detection (CAD) program.
      The CAD algorithm was structured to process nodules that were categorized into
      three types: isolated, juxtapleural, and juxtavascular. Overall sensitivity for
      nodule detection with the CAD program was 95.1% (156 of 164 nodules). The
      sensitivity according to nodule size was 91.2% (52 of 57 nodules) for nodules 3
      mm to less than 5 mm and 97.2% (104 of 107 nodules) for nodules 5 mm and larger.
      The number of false-positive detections per patient was 6.9 for false nodule
      structures 3 mm and larger and 4.0 for false nodule structures 5 mm and larger.

PMID- 15955863
TI  - Automated detection of pulmonary nodules on CT images: effect of section
      thickness and reconstruction interval--initial results.
AB  - Institutional review board approval was obtained. Informed patient consent was
      not required. Study was compliant with HIPAA. Performance of an automated
      pulmonary nodule detection program was evaluated on multi-detector row CT images
      that were acquired once but reconstructed retrospectively at different section
      thicknesses and reconstruction intervals. From raw CT data in 10 patients with
      pulmonary nodules, three sets of CT images were reconstructed separately in each
      patient by selecting two section thickness and reconstruction combinations,
      respectively: thin group, 1 and 1 mm; overlap group, 5 and 1 mm; and thick group,
      5 and 5 mm. Nodules 3 mm in diameter and larger were detected in each group (thin
      group, 126 nodules; overlap group, 121 nodules; and thick group, 114 nodules) by
      means of consensus of two radiologists. Findings were used as the reference
      standard for evaluation of the computer-aided detection (CAD) program.
      Sensitivity and number of false-positive findings per patient by CAD were: thin
      group, 95.2% (120 of 126 nodules) and 5.4 findings; overlap group, 94.2% (114 of
      121 nodules) and 9.7 findings; and thick group, 88.6% (101 of 114 nodules) and
      23.6 findings, indicating that nodule detection degraded with increase in section
      thickness but improved substantially with a small reconstruction interval.

PMID- 15955864
TI  - Indeterminate ovarian mass at US: incremental value of second imaging test for
      characterization--meta-analysis and Bayesian analysis.
AB  - PURPOSE: To compare value of current diagnostic strategies in assessment of
      changes in posttest probability of ovarian cancer when menopausal status and
      combination and sequence of diagnostic imaging tests are considered. MATERIALS
      AND METHODS: Prevalence of ovarian cancer according to menopausal status in women
      with an ovarian mass and performance of combined gray-scale and Doppler
      ultrasonography (US), computed tomography (CT), and non-enhanced magnetic
      resonance (MR) imaging and contrast material-enhanced MR imaging after
      indeterminate results at gray-scale US were derived from meta-analysis by using
      MEDLINE database and institutional data. Study was approved by the institutional
      review board of University Hospital Geneva, Geneva, Switzerland; informed consent
      was waived. Posttest probability values were computed through Bayesian analysis
      and Monte Carlo simulation after initial gray-scale US and secondary combined
      gray-scale and Doppler US, CT, or MR imaging, while dependence of test results
      among imaging modalities was considered. Changes in posttest probability were
      compared among imaging modalities with summary receiver operating characteristic
      curves. RESULTS: Prevalence of ovarian cancer was 8.75% in premenopausal women
      and 32.40% in postmenopausal women with an ovarian mass. After characterization
      with initial gray-scale US, posttest probability in pre- and postmenopausal women
      changed, respectively, to 25% and 63% for indeterminate results and to 2% and 7%
      for benign results. Subsequent use of combined gray-scale and Doppler US, CT, or
      MR imaging had significant higher positive and lower negative posttest
      probability than did use of gray-scale US alone. In women with an indeterminate
      initial US result, posttest probability decreased after secondary testing with
      benign results for all imaging modalities to 2% in premenopausal women and to 8%
      10% in postmenopausal women. After secondary testing for suspicious lesions,
      posttest probability increased more after non-enhanced (premenopausal women, 70%;
      postmenopausal women, 92%) or contrast-enhanced MR imaging (premenopausal women,
      80%; postmenopausal women, 95%) than it did after combined gray-scale and Doppler
      US (premenopausal women, 30%; postmenopausal women, 69%) or CT (premenopausal
      women, 38%; postmenopausal women, 76%) (P < .001). CONCLUSION: In women with an
      indeterminate ovarian mass at gray-scale US, MR imaging results contributed to
      change in probability of ovarian cancer in both pre- and postmenopausal women
      more than did CT or combined gray-scale and Doppler US results.

PMID- 15955865
TI  - Rational development of histone deacetylase inhibitors as anticancer agents: a
      review.
AB  - The epigenome is defined by DNA methylation patterns and the associated post
      translational modifications of histones. This histone code determines the
      expression status of individual genes dependent upon their localization on the
      chromatin. The histone deacetylases (HDACs) play a major role in keeping the
      balance between the acetylated and deacetylated states of chromatin and
      eventually regulate gene expression. Recent developments in understanding the
      cancer cell cycle, specifically the interplay with chromatin control, are
      providing opportunities for developing mechanism-based therapeutic drugs.
      Inhibitors of HDACs are under considerable exploration, in part because of their
      potential roles in reversing the silenced genes in transformed tumor cells by
      modulating transcriptional processes. This review is an effort to summarize the
      nonclinical and clinical status of HDAC inhibitors currently under development in
      anticancer therapy.

PMID- 15955866
TI  - The Gln4863Ala mutation within a putative, pore-lining trans-membrane helix of
      the cardiac ryanodine receptor channel alters both the kinetics of ryanoid
      interaction and the subsequent fractional conductance.
AB  - The specific, high-affinity interaction of the plant toxin ryanodine with its
      molecular target the ryanodine receptor channel (RyR) has been instrumental in
      RyR research. Alanine scanning of putative pore regions of mouse RyR2 has
      highlighted the amino acid Gln4863, predicted to lie within trans-membrane helix
      TM10, as an important determinant of ryanodine binding. We have investigated the
      effects of several ryanodine derivatives, guanidinopropionylryanodine, 21-p
      nitrobenzoylamino-9alpha-hydroxyryanodine, 8beta-amino-9alpha-hydroxyryanodine,
      and 21-amino-9alpha-hydroxyryanodine, with the mouse Q4863A RyR2 mutant at the
      single-channel level. Our results demonstrate that the rate of dissociation of
      all ryanoids investigated is increased by the mutation. The modification of
      channel function after ryanoid binding is qualitatively similar for wild-type and
      mutant, but in several cases, single-channel conductances were increased with
      Q4863A. These novel findings have been interpreted within the framework of
      existing comparative molecular field analysis studies on ryanoids. We suggest
      that replacement of a glutamine by an alanine residue at position 4863 causes
      RyR2 to simultaneously alter interactions with both ends of the ryanoid molecule.

PMID- 15955867
TI  - Uridine binding and transportability determinants of human concentrative
      nucleoside transporters.
AB  - Human concentrative nucleoside transporters 1, 2, and 3 (hCNT1, hCNT2, and hCNT3)
      exhibit different functional characteristics, and a better understanding of their
      permeant selectivities is critical for development of nucleoside analog drugs
      with optimal pharmacokinetic properties. In this study, the sensitivity of a high
      throughput yeast expression system used previously for hCNT1 and hCNT3 was
      improved and used to characterize determinants for interaction of uridine (Urd)
      with hCNT2. The observed changes of binding energy between hCNT2 and different
      Urd analogs suggested that it interacts with C3'-OH, C5'-OH, and N3-H of Urd. The
      C2' and C5 regions of Urd played minor but significant roles for Urd-hCNT2
      binding, possibly through Van der Waals interactions. Because the yeast assay
      only provided information about potential transportability, the permeant
      selectivities of recombinant hCNT1, hCNT2, and hCNT3 produced in Xenopus laevis
      oocytes were investigated using a two-electrode voltage clamp assay. hCNT1
      mediated transport was sensitive to modifications of the N3, C3', and C5'
      positions of Urd. hCNT2 showed some tolerance for transporting Urd analogs with
      C2' or C5 modifications, little tolerance for N3 modifications, and no tolerance
      for any modifications at C3' or C5' of Urd. Although hCNT3 was sensitive to C3'
      modifications, it transported a broad range of variously substituted Urd analogs.
      The transportability profiles identified in this study, which reflected the
      binding profiles well, should prove useful in the development of anticancer and
      antiviral therapies with nucleoside drugs that are permeants of members of the
      hCNT protein family.

PMID- 15955868
TI  - Effects of quinine, quinidine, and chloroquine on alpha9alpha10 nicotinic
      cholinergic receptors.
AB  - In this study, we report the effects of the quinoline derivatives quinine, its
      optical isomer quinidine, and chloroquine on alpha9alpha10-containing nicotinic
      acetylcholine receptors (nAChRs). The compounds blocked acetylcholine (ACh)
      evoked responses in alpha9alpha10-injected Xenopus laevis oocytes in a
      concentration-dependent manner, with a rank order of potency of chloroquine (IC50
      = 0.39 microM) > quinine (IC50 = 0.97 microM) approximately quinidine (IC50= 1.37
      microM). Moreover, chloroquine blocked ACh-evoked responses on rat cochlear inner
      hair cells with an IC50 value of 0.13 microM, which is within the same range as
      that observed for recombinant receptors. Block by chloroquine was purely
      competitive, whereas quinine inhibited ACh currents in a mixed competitive and
      noncompetitive manner. The competitive nature of the blockage produced by the
      three compounds was confirmed by equilibrium binding experiments using
      [3H]methyllycaconitine. Binding affinities (Ki values) were 2.3, 5.5, and 13.0
      microM for chloroquine, quinine, and quinidine, respectively. Block by quinine
      was found to be only slightly voltage-dependent, thus precluding open-channel
      block as the main mechanism of interaction of quinine with alpha9alpha10 nAChRs.
      The present results add to the pharmacological characterization of alpha9alpha10
      containing nicotinic receptors and indicate that the efferent olivocochlear
      system that innervates the cochlear hair cells is a target of these ototoxic
      antimalarial compounds.

PMID- 15955869
TI  - Increased Bcl2 expression by antisense oligoribonucleotides targeting the adenine
      uridine-rich element motif.
AB  - RNA has become a promising target for pharmacological purposes. Most current
      strategies are directed toward down-regulating its functions. In this study, we
      provide evidence of the up-regulation of messenger RNA in a sequence-specific
      manner. The bcl2 (b)-ARE (adenine-uridine-rich element) in the 3'-untranslated
      region of the b-RNA that regulates the rate of RNA degradation has been targeted
      with three chemically modified oligoribonucleotides designed in the antisense
      orientation (asORNs). The three asORNs were studied by a cell-free degradation
      assay. All three slowed the rate of RNA decay in a dose-response fashion, they
      were specific to the b-ARE, and two of them were individually effective. asORNs
      were then transfected into the malignant cells in culture and b-RNA half-life was
      measured by real-time reverse transcriptase-polymerase chain reaction. We showed
      that by stabilizing b-RNA the three asORNs increased the expression of b-RNA and
      of the relevant protein in a dose-response fashion.

PMID- 15955870
TI  - CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.
AB  - The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1
      allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an
      intronic sequence (exon 3B) containing premature termination codons (PTCs)
      between exons 3 and 4. Two models were used to investigate the degradation of
      CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6
      transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2
      cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5
      mRNA decay. Splice variants containing exon 3B were more unstable than wild-type
      (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in
      transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of
      exon 3B-containing splice variants, suggesting the participation of nonsense
      mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1
      small interfering RNA was used to impair the NMD mechanism, the decay of the
      splice variant was reduced, confirming the involvement of NMD in the degradation
      of CYP3A5 splice variants. Induction could represent a source of variability for
      CYP3A5 expression and could modify the proportion of splice variants. The extent
      of CYP3A5 induction was investigated after exposure to barbiturates or steroids:
      CYP3A4 was markedly induced in a pediatric population compared with untreated
      neonates. However, no effect could be detected in either the total CYP3A5 RNA,
      the proportion of splice variant RNA, or the protein level. Therefore, in these
      carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in
      carriers of CYP3A5*3/*3.

PMID- 15955871
TI  - Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin.
AB  - Pitavastatin, a novel potent 3-hydroxymethylglutaryl coenzyme A reductase
      inhibitor, is distributed selectively to the liver and excreted into bile in
      unchanged form in rats. We reported previously that the hepatic uptake is mainly
      mediated by organic anion transporting polypeptide (OATP) 1B1, whereas the
      biliary excretion mechanism remains to be clarified. In the present study, we
      investigated the role of breast cancer resistance protein (BCRP) in the biliary
      excretion of pitavastatin. The ATP-dependent uptake of pitavastatin by human and
      mouse BCRP-expressing membrane vesicles was significantly higher compared with
      that by control vesicles with Km values of 5.73 and 4.77 microM, respectively.
      The biliary excretion clearance of pitavastatin in Bcrp1-/- mice was decreased to
      one-tenth of that in control mice. The biliary excretion of pitavastatin was
      unchanged between control and Eisai hyperbilirubinemic rats, indicating a minor
      contribution of multidrug resistance-associated protein (Mrp) 2. This observation
      differs radically from that for a more hydrophilic statin, pravastatin, of which
      biliary excretion is largely mediated by Mrp2. These data suggest that the
      biliary clearance of pitavastatin can be largely accounted for by BCRP in mice.
      In the case of humans, transcellular transport of pitavastatin was determined in
      the Madin-Darby canine kidney II cells expressing OATP1B1 and human canalicular
      efflux transporters. A significant basal-to-apical transport of pitavastatin was
      observed in OATP1B1/MDR1 and OATP1B1/MRP2 double transfectants as well as
      OATP1B1/BCRP double transfectants, implying the involvement of multiple
      transporters in the biliary excretion of pitavastatin in humans. This is in
      contrast to a previous belief that the biliary excretion of statins is mediated
      mainly by MRP2.

PMID- 15955872
TI  - CYP2C9 genotype-dependent effects on in vitro drug-drug interactions: switching
      of benzbromarone effect from inhibition to activation in the CYP2C9.3 variant.
AB  - The CYP2C9.3 variant exhibits marked decreases in substrate turnover compared
      with the wild-type enzyme, but little is known regarding the effect this variant
      form may have on the occurrence of drug-drug interactions. To examine this
      possibility, the effect of the potent CYP2C9 inhibitor, benzbromarone, was
      studied with regard to CYP2C9.1- and CYP2C9.3-mediated flurbiprofen metabolism to
      evaluate whether the variant enzyme exhibits differential inhibition kinetics.
      Although benzbromarone inhibited CYP2C9.1 activity as expected, CYP2C9.3-mediated
      flurbiprofen 4'-hydroxylation was activated in the presence of benzbromarone. T1
      relaxation studies revealed little change in distances of flurbiprofen protons
      from the heme iron of either CYP2C9.1 or CYP2C9.3 in the presence of
      benzbromarone compared with flurbiprofen alone. Spectral binding studies were
      also performed to investigate whether benzbromarone affected substrate binding,
      with the addition of benzbromarone having little effect on flurbiprofen-binding
      affinity in both CYP2C9.1 and CYP2C9.3. Docking studies with the 2C9.1 structure
      crystallized with a closed active site identified multiple but overlapping
      subsites with sufficient space for benzbromarone binding in the enzyme when
      flurbiprofen was positioned closest to the heme. If the closed conformation of
      2C9.3 is structurally similar to 2C9.1, as expected for the conservative I359L
      mutation, then the dynamics of benzbromarone binding may account for the
      switching of drug interaction effects. In conclusion, the I359L amino acid
      substitution found in CYP2C9.3 not only reduces metabolism compared with CYP2C9.1
      but can also dramatically alter inhibitor effects, suggesting that differential
      degrees of drug inhibition interactions may occur in individuals with this
      variant form of CYP2C9.

PMID- 15955873
TI  - Heme regulates allosteric activation of the Slo1 BK channel.
AB  - Large conductance calcium-dependent (Slo1 BK) channels are allosterically
      activated by membrane depolarization and divalent cations, and possess a rich
      modulatory repertoire. Recently, intracellular heme has been identified as a
      potent regulator of Slo1 BK channels (Tang, X.D., R. Xu, M.F. Reynolds, M.L.
      Garcia, S.H. Heinemann, and T. Hoshi. 2003. Nature. 425:531-535). Here we
      investigated the mechanism of the regulatory action of heme on heterologously
      expressed Slo1 BK channels by separating the influences of voltage and divalent
      cations. In the absence of divalent cations, heme generally decreased ionic
      currents by shifting the channel's G-V curve toward more depolarized voltages and
      by rendering the curve less steep. In contrast, gating currents remained largely
      unaffected by heme. Simulations suggest that a decrease in the strength of
      allosteric coupling between the voltage sensor and the activation gate and a
      concomitant stabilization of the open state account for the essential features of
      the heme action in the absence of divalent ions. At saturating levels of divalent
      cations, heme remained similarly effective with its influence on the G-V
      simulated by weakening the coupling of both Ca(2+) binding and voltage sensor
      activation to channel opening. The results thus show that heme dampens the
      influence of allosteric activators on the activation gate of the Slo1 BK channel.
      To account for these effects, we consider the possibility that heme binding
      alters the structure of the RCK gating ring and thereby disrupts both Ca(2+)- and
      voltage-dependent gating as well as intrinsic stability of the open state.

PMID- 15955874
TI  - An electrostatic engine model for autoinhibition and activation of the epidermal
      growth factor receptor (EGFR/ErbB) family.
AB  - We propose a new mechanism to explain autoinhibition of the epidermal growth
      factor receptor (EGFR/ErbB) family of receptor tyrosine kinases based on a
      structural model that postulates both their juxtamembrane and protein tyrosine
      kinase domains bind electrostatically to acidic lipids in the plasma membrane,
      restricting access of the kinase domain to substrate tyrosines. Ligand-induced
      dimerization promotes partial trans autophosphorylation of ErbB1, leading to a
      rapid rise in intracellular [Ca(2+)] that can activate calmodulin. We postulate
      the Ca(2+)/calmodulin complex binds rapidly to residues 645--660 of the
      juxtamembrane domain, reversing its net charge from +8 to -8 and repelling it
      from the negatively charged inner leaflet of the membrane. The repulsion has two
      consequences: it releases electrostatically sequestered phosphatidylinositol 4,5
      bisphosphate (PIP(2)), and it disengages the kinase domain from the membrane,
      allowing it to become fully active and phosphorylate an adjacent ErbB molecule or
      other substrate. We tested various aspects of the model by measuring ErbB
      juxtamembrane peptide binding to phospholipid vesicles using both a
      centrifugation assay and fluorescence correlation spectroscopy; analyzing the
      kinetics of interactions between ErbB peptides, membranes, and Ca(2+)/calmodulin
      using fluorescence stop flow; assessing ErbB1 activation in Cos1 cells; measuring
      fluorescence resonance energy transfer between ErbB peptides and PIP(2); and
      making theoretical electrostatic calculations on atomic models of membranes and
      ErbB juxtamembrane and kinase domains.

PMID- 15955875
TI  - Initial coupling of binding to gating mediated by conserved residues in the
      muscle nicotinic receptor.
AB  - We examined functional consequences of intrasubunit contacts in the nicotinic
      receptor alpha subunit using single channel kinetic analysis, site-directed
      mutagenesis, and structural modeling. At the periphery of the ACh binding site,
      our structural model shows that side chains of the conserved residues alphaK145,
      alphaD200, and alphaY190 converge to form putative electrostatic interactions.
      Structurally conservative mutations of each residue profoundly impair gating of
      the receptor channel, primarily by slowing the rate of channel opening. The
      combined mutations alphaD200N and alphaK145Q impair channel gating to the same
      extent as either single mutation, while alphaK145E counteracts the impaired
      gating due to alphaD200K, further suggesting electrostatic interaction between
      these residues. Interpreted in light of the crystal structure of acetylcholine
      binding protein (AChBP) with bound carbamylcholine (CCh), the results suggest in
      the absence of ACh, alphaK145 and alphaD200 form a salt bridge associated with
      the closed state of the channel. When ACh binds, alphaY190 moves toward the
      center of the binding cleft to stabilize the agonist, and its aromatic hydroxyl
      group approaches alphaK145, which in turn loosens its contact with alphaD200. The
      positional changes of alphaK145 and alphaD200 are proposed to initiate the
      cascade of perturbations that opens the receptor channel: the first perturbation
      is of beta-strand 7, which harbors alphaK145 and is part of the signature Cys
      loop, and the second is of beta-strand 10, which harbors alphaD200 and connects
      to the M1 domain. Thus, interplay between these three conserved residues relays
      the initial conformational change from the ACh binding site toward the ion
      channel.

PMID- 15955876
TI  - Functionally active t1-t1 interfaces revealed by the accessibility of
      intracellular thiolate groups in kv4 channels.
AB  - Gating of voltage-dependent K(+) channels involves movements of membrane-spanning
      regions that control the opening of the pore. Much less is known, however, about
      the contributions of large intracellular channel domains to the conformational
      changes that underlie gating. Here, we investigated the functional role of
      intracellular regions in Kv4 channels by probing relevant cysteines with thiol
      specific reagents. We find that reagent application to the intracellular side of
      inside-out patches results in time-dependent irreversible inhibition of Kv4.1 and
      Kv4.3 currents. In the absence or presence of Kv4-specific auxiliary subunits,
      mutational and electrophysiological analyses showed that none of the 14
      intracellular cysteines is essential for channel gating. C110, C131, and C132 in
      the intersubunit interface of the tetramerization domain (T1) are targets
      responsible for the irreversible inhibition by a methanethiosulfonate derivative
      (MTSET). This result is surprising because structural studies of Kv4-T1 crystals
      predicted protection of the targeted thiolate groups by constitutive high
      affinity Zn(2+) coordination. Also, added Zn(2+) or a potent Zn(2+) chelator
      (TPEN) does not significantly modulate the accessibility of MTSET to C110, C131,
      or C132; and furthermore, when the three critical cysteines remained as possible
      targets, the MTSET modification rate of the activated state is approximately 200
      fold faster than that of the resting state. Biochemical experiments confirmed the
      chemical modification of the intact alpha-subunit and the purified tetrameric T1
      domain by MTS reagents. These results conclusively demonstrate that the T1--T1
      interface of Kv4 channels is functionally active and dynamic, and that critical
      reactive thiolate groups in this interface may not be protected by Zn(2+)
      binding.

PMID- 15955877
TI  - The tarantula toxin psalmotoxin 1 inhibits acid-sensing ion channel (ASIC) 1a by
      increasing its apparent H+ affinity.
AB  - Acid-sensing ion channels (ASICs) are ion channels activated by extracellular
      protons. They are involved in higher brain functions and perception of pain,
      taste, and mechanical stimuli. Homomeric ASIC1a is potently inhibited by the
      tarantula toxin psalmotoxin 1. The mechanism of this inhibition is unknown. Here
      we show that psalmotoxin 1 inhibits ASIC1a by a unique mechanism: the toxin
      increases the apparent affinity for H(+) of ASIC1a. Since ASIC1a is activated by
      H(+) concentrations that are only slightly larger than the resting H(+)
      concentration, this increase in H(+) affinity is sufficient to shift ASIC1a
      channels into the desensitized state. As activation of ASIC1a has recently been
      linked to neurodegeneration associated with stroke, our results suggest chronic
      desensitization of ASIC1a by a slight increase of its H(+) affinity as a possible
      way of therapeutic intervention in stroke.

PMID- 15955878
TI  - Multiple facets of maxi-k+ channels: the heme connection.

PMID- 15955879
TI  - The Sperminator needed a magic number.

PMID- 15955880
TI  - Spermatogonial stem cell isolation, storage, and transplantation.

PMID- 15955882
TI  - Lions, tigers, and pandas, oh my.

PMID- 15955883
TI  - Diabetes in a bearded woman.

PMID- 15955884
TI  - A review of the physical and chemical properties of human semen and the
      formulation of a semen simulant.
AB  - A fluid medium was developed to simulate the salient physical and chemical
      properties of human semen. The composition of the medium was based upon an
      extensive review of the literature on constituents of human semen. In choosing
      the ingredients for this medium, the goal was to emphasize properties that
      influence interactions of human semen with topical contraceptive, prophylactic,
      or therapeutic products. Among these properties, pH and buffering capacity,
      osmolarity, ionic strength, and rheological properties play dominant roles in the
      physico-chemical processes that govern drug release kinetics and delivery vehicle
      distribution.

PMID- 15955885
TI  - Chimpanzee (Pan troglodytes) spermatozoa osmotic tolerance and cryoprotectant
      permeability characteristics.
AB  - Osmotic properties of chimpanzee spermatozoa were studied at 22 degrees C. An
      electronic particle counter was used to determine the isosmotic cell volume, and
      the volume response after exposure to four commonly used cryoprotectants:
      dimethyl sulfoxide, glycerol, propylene glycol, and ethylene glycol. The data
      were analyzed to determine the hydraulic conductivity and the permeability
      coefficients for the four cryoprotectants. The osmotically inactive volume
      fraction was determined using a Boyle van't Hoff plot of cells exposed to sodium
      chloride solutions. A computer-assisted semen analysis system was used to
      determine the osmotic tolerance of chimp spermatozoa, as well as the effects of a
      one-step addition and removal of 1 M permeating cryoprotectant on sperm motility.
      The isosmotic volume of chimpanzee sperm is 27.7 microm3. The osmotically
      inactive cell fraction is 69%. Hydraulic conductivity was higher in the presence
      of ethylene glycol: 4.09 +/- 0.76 (mean +/- SEM) and propylene glycol: 3.91 +/-
      0.71 as compared to dimethyl sulfoxide: 3.49 +/- 0.79 and glycerol: 2.83 +/- 0.40
      microm/min per atmosphere. The permeability of chimpanzee sperm in ethylene
      glycol (2.18 +/- 0.40 x 10(-3) cm/min) and propylene glycol (1.75 +/- 0.17 x 10(
      3) cm/min) was higher than in glycerol (1.42 +/- 0.12 x 10(-3) cm/min) and
      dimethyl sulfoxide (0.82 +/- 0.015 x 10(-3) cm/min). Although chimpanzee sperm
      tolerated osmotic stress in the range of 169-400 mOsm very well, loss of motility
      was observed as the solution concentrations diverged from isosmotic condition.
      Exposure to the four cryoprotectants at 1 M did not cause a significant reduction
      in sperm motility. This information on membrane permeability characteristics and
      cryoprotectant tolerance will aid in designing more reliable cryopreservation
      protocols for chimpanzee sperm.

PMID- 15955886
TI  - The stimulatory role of estrogen on sperm motility in the male golden hamster
      (Mesocricetus auratus).
AB  - To clarify the physiological roles of estrogens in the regulation of sperm
      motility in the golden hamster, two different approaches were used. In the first
      experiment, silastic tubes containing either low (low E2 group) or high (high E2
      group) amount of estradiol-17beta were implanted (Exp 1). In the second
      experiment, male golden hamsters were actively immunized against estradiol-17beta
      (Exp 2). In Exp 1, all sperm motility parameters (including motility, straight
      velocity, curvilinear velocity, beat/cross frequency, and mean amplitude of
      lateral head displacement) were significantly increased except linear index in
      the high E2 group as compared with controls at 20 days after the treatment. In
      the high E2 group, plasma concentrations of luteinizing hormone (LH)
      significantly increased, whereas levels of circulating testosterone decreased
      significantly. Plasma concentrations of follicle-stimulating hormone (FSH) and
      immunoreactive inhibin were not affected by the treatment with estradiol-17beta.
      In the Exp 2, titer of circulating antibodies to estradiol-17beta consistently
      increased after the second immunization until the end of experiment (16 weeks).
      The sperm motility, straight velocity, and curvilinear velocity were
      significantly decreased after active immunization to estradiol-17beta.
      Concentrations of circulating LH and FSH were also decreased significantly by the
      treatment. In conclusion, the current observations indicate that estradiol-17beta
      affects sperm motility in adult male golden hamsters.

PMID- 15955887
TI  - Cellular localization of GABA and GABAB receptor subunit proteins during
      spermiogenesis in rat testis.
AB  - The GABAergic system, a major inhibitory regulator in the central nervous system,
      may also play important roles in peripheral nonneuronal tissues and cells. Recent
      studies showed that GABAB receptor is expressed in testis and sperm. To
      understand the role of the GABAergic system in spermiogenesis, we examined
      cellular localization of GABA and GABAB receptor subunits in rat spermatids by
      immunocytochemistry. Immunoreactivity for GABA was detected around acrosomal
      granules of spermatids during the Golgi and cap phases. GABAB1 immunoreactivity
      was observed in the acrosomal vesicle of spermatids in Golgi phase, and during
      cap phase, this reactivity expanded to the entire region of the acrosome covering
      the nuclear membrane. The level of reactivity decreased gradually with maturation
      of spermatids. In contrast, GABAB2 immunoreactivity was not observed in
      spermatids during Golgi phase but was detected in the equatorial region during
      cap phase. Both GABA immunoreactivity and GABAB2 immunoreactivity were
      transferred to the residual cytoplasm during the release of spermatozoa. Electron
      microscopic immunocytochemistry revealed that, during cap phase, GABA and GABAB1
      were distributed within the whole acrosomal vesicle but not in the acrosomal
      granule. GABAB2 immunoreactivity was observed in the narrow space between the
      inner acrosomal and nuclear membrane and was limited to the equatorial region of
      the spermatid head. These results indicate that the GABAergic system might be
      involved in regulation of spermiogenesis.

PMID- 15955888
TI  - Follicle-stimulating hormone receptor gene haplotype distribution in
      normozoospermic and azoospermic men.
AB  - The human follicle-stimulating hormone (FSH) receptor (FSHR) gene possesses
      single nucleotide polymorphisms (SNP) in exon 10, which influence serum FSH
      levels in women, but not in men. In the present study we extend our previous
      investigation and for the first time analyze a novel, common SNP at position -29
      of the FSHR core promoter in men. The SNP in codon 680 was analyzed in 438 men
      with nonobstructive azoospermia and in 304 controls. The SNP in codon 307 and at
      position -29 was analyzed in 345 men with nonobstructive azoospermia and 186
      controls. SNPs were determined by allelic discrimination. No significant
      difference in the frequency of the polymorphism at position 680 and serum FSH
      levels was found. At position -29 (A/G) the A(-29) allele was less frequent than
      the G(-29) allele both in controls (25% vs 75%) and in patients (30% vs 70%) (P
      not significant). Together the three SNPs form four discrete haplotypes (A-Thr
      Asn, G-Thr-Asn, A-Ala-Ser, and G-Ala-Ser) occurring in 10 combinations. A
      statistically significant difference in the allelic distribution between controls
      and azoospermic men was found (P < .05 by chi2 test). The A-Ala-Ser allele was
      more frequent in patients (9.1%) than in controls (5.4%), whereas the G-Thr-Asn
      allele was less frequent in patients (33.1%) than in controls (40.6%) (P < .01 by
      Fisher's exact test). No significant correlation between serum FSH levels and
      FSHR allele was found. We conclude that the FSHR haplotype does not associate
      with different serum FSH levels but it is differently distributed in normal and
      azoospermic men. The A-Ala-Ser and the G-Thr-Asn allele might represent genetic
      factors contributing to phenotypic expression of severe spermatogenetic
      impairment.

PMID- 15955889
TI  - Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced
      prostate specific antigen gene expression and prostate tumor cell growth by
      estrogens.
AB  - Androgens via the androgen receptor (AR) play crucial roles in prostate
      physiology and pathophysiology. These androgen actions can be either inhibited or
      potentiated by estrogens. The mechanisms of these seemingly opposing estrogen
      effects are unclear. We studied the effects of estrogens on the modulation of
      androgen induction of prostate specific antigen (PSA) gene expression and
      prostate tumor cell growth. Cotransfection analyses in CV-1, DU-145, and PC-3
      cells showed that dihydrotestosterone (DHT)-induced PSA transcription activity
      was inhibited by 17beta-estradiol, diethylstilbestrol, ICI182780, and 17alpha
      estradiol, but not by tamoxifen via estrogen receptor alpha (ERalpha). In the
      presence of ERbeta, 17beta-estradiol and diethylstilbestrol had no significant
      effect, while 17alpha-estradiol inhibited and ICI182780 and tamoxifen potentiated
      DHT action. When both ERalpha and ERbeta were present, all ER-ligands except
      tamoxifen inhibited DHT action. The inhibition of DHT action by 17beta-estradiol
      via ERalpha was mainly dependent on the DNA binding domain, while the 17alpha
      estradiol effect was mainly dependent on the ERalpha carboxyl terminus. Treatment
      with DHT in LAPC-4 prostate tumor cells that express a wild-type AR and both
      ERbeta and ERalpha greatly increased the PSA gene expression and cell growth.
      These DHT effects were significantly attenuated by the addition of 17alpha
      estradiol, 17beta-estradiol, or cyproterone acetate in a dose-dependent manner.
      These results indicate that estrogens produce an ER-isoform- and ER-ligand
      specific modulation of DHT induction of PSA gene expression and prostate tumor
      cell growth, providing a molecular basis for designing favorable agents for the
      prevention and control of prostate cancer.

PMID- 15955891
TI  - Identification of human HAPRIN potentially involved in the acrosome reaction.
AB  - The acrosome reaction in sperm is an exocytotic event required for fertilization.
      Previously, we isolated a novel haploid-germ-cell-specific gene in the mouse;
      this gene, named haprin, encodes the RING-finger, B-box-type zinc finger and
      coiled-coil domain (RBCC) motif protein and may be involved in the acrosome
      reaction. Here we report the molecular cloning and characterization of a human
      haprin ortholog. The deduced amino acid sequence of human haprin had 91% identity
      with the mouse ortholog. Transcripts of human haprin were detected exclusively in
      the testes. Western blot and immunocytochemical analyses detected HAPRIN protein
      in the testes and sperm. The protein was localized in the acrosomal region of
      sperm and disappeared after the acrosome reaction. Our results indicate that the
      function of HAPRIN is highly conserved in humans and mice and that the protein
      could play an important role in the regulation of the acrosome reaction.

PMID- 15955892
TI  - The proacrosin binding protein, sp32, is tyrosine phosphorylated during
      capacitation of pig sperm.
AB  - Mammalian sperm must undergo capacitation, a preparation period in the female
      reproductive tract or in vitro, in order to fertilize. We have previously
      described a Mr 32 000 tyrosine phosphorylated protein, "p32," that appears in pig
      sperm during capacitation. The identity of p32 remains unknown; if and how it is
      involved during capacitation is not understood. The objective of the present
      study was to identify p32 by proteomic techniques. Western blotting of proteins
      separated successively under nonreducing and then reducing conditions showed the
      appearance of the tyrosine phosphorylated p32 only when sperm were incubated in
      capacitating conditions. The spot was sequenced by mass spectrometry/mass
      spectrometry and identified as "sp32," a protein implicated in proacrosin
      maturation. The same membranes probed with anti-sp32 antibody demonstrated that
      sp32 is present in both noncapacitating and capacitating conditions and revealed
      exactly the same spot as p32. Immunoprecipitation with either anti
      phosphotyrosine or anti-sp32 antibody corroborated these results. Indirect
      immunofluorescence with anti-phosphotyrosine antibody or anti-sp32 antibody show
      similar labeling of capacitated sperm, supporting the hypothesis that p32 is a
      tyrosine phosphorylated form of sp32. After ionophore treatment to induce the
      acrosome reaction, anti-sp32 and anti-phosphotyrosine labeling on the acrosome
      disappeared. These results demonstrate that sp32, a (pro)acrosin binding protein,
      is the p32, a tyrosine phosphorylated protein related to capacitation. We will
      now focus on the significance of tyrosine phosphorylation on sp32 function during
      fertilization-related events.

PMID- 15955893
TI  - Hybrid GPCR/cadherin (Celsr) proteins in rat testis are expressed with cell type
      specificity and exhibit differential Sertoli cell-germ cell adhesion activity.
AB  - Spermatogenesis requires Sertoli cell-germ cell adhesion for germ cell survival
      and maturation. Cadherins are a diverse superfamily of adhesion proteins;
      structurally unique members of this superfamily (celsr cadherins) are hybrid
      molecules containing extracellular cadherin repeats connected to a G protein
      coupled receptor transmembrane motif. Here we demonstrate postnatal testicular
      mRNA expression of the 3 celsr paralogs (celsr1, celsr2, and celsr3), protein
      localization of celsr2 and celsr3, and functional analysis of celsr2 adhesion
      activity in primary Sertoli cell-germ cell co-cultures. Evaluation of celsr mRNA
      levels during a postnatal time course indicated that celsr1 and celsr2 were
      Sertoli cell and/or early-stage germ cell products, whereas celsr3 was expressed
      in later-stage germ cells. Cell type-specific expression was verified using the
      Sertoli cell line 93RS2, where celsr1 and celsr2 mRNA, but not celsr3, were
      detected. Immunostaining of testicular cryosections resulted in celsr2 protein
      localization to a spokelike pattern in the basal seminiferous epithelium and
      punctate figures in the apical epithelium, consistent with both Sertoli cell and
      germ cell expression. Celsr3 localized to punctate structures in the adluminal
      epithelium from postnatal day 40, consistent with elongate spermatid expression.
      The subcellular localization of celsr2 was examined further to define its
      localization in Sertoli cells and germ cells. Celsr2 localized to the Golgi
      complex in Sertoli cells and germ cells. In addition, germ cell celsr2 localized
      to a rab7-positive structure, which may be an endocytic compartment. Neither
      celsr2 nor celsr3 immunostaining was present at classic cadherin-based adhesion
      junctions. Nonetheless, the addition of a recombinant celsr2 protein fragment
      consisting of extracellular cadherin domains 4 through 8 to Sertoli cell-germ
      cell co-cultures resulted in germ cell detachment from Sertoli cells.
      Collectively, these data indicate that celsr cadherins have a cell type-specific
      expression pattern, and celsr2 may mediate Sertoli cell-germ cell adhesion
      outside of classic cadherin-based adhesion junctions.

PMID- 15955894
TI  - Immunocytochemical localization and biochemical characterization of two seminal
      plasma proteins that protect ram spermatozoa against cold shock.
AB  - We have already shown that seminal plasma proteins in the ram can repair cold
      shock sperm membrane damage and that the addition of seminal plasma proteins
      before cold-shock treatment prevents sperm membrane injury. In this study, we
      prove that 2 protein bands of approximately 14 (P14) and 20 (P20) kd isolated
      from seminal plasma are responsible for this protective effect. In vitro
      capacitation (CA) and acrosome reaction (AR) modified the content of both
      proteins on the sperm surface. P20 release began at the beginning of CA, and the
      induction of the AR accounted for an additional release of both proteins; not
      more than 35% of these proteins remained on acrosome-reacted sperm. Cytochemical
      analysis detected that there are several binding sites for P14 and P20 on the
      sperm surface and that membrane alterations induced by CA and the AR accounted
      for the loss and redistribution of both proteins to the equatorial and
      postequatorial regions. The P14-sequenced fragment showed a high homology with
      several seminal plasma proteins of different species and contained the FN 2
      domain like bovine PDC-109. However, the sequence of the P20 fragment was not
      homologous with any reported protein. By immunochemical analysis, we obtained
      evidence that P14 is phosphorylated in serine and threonine residues and that P20
      is a glycosylated protein. These results suggest that both proteins are involved
      in sperm CA and gamete interaction, first by stabilizing the sperm membrane and
      then by participating in CA in the female reproductive tract. The protective
      effect of P14 and P20 could be related to their decapacitating role.

PMID- 15955896
TI  - Processing color figures: that was then, this is now.

PMID- 15955895
TI  - Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking
      men.
AB  - Oxidative stress is detrimental to sperm function and a significant factor in the
      etiology of male infertility. This report examines the association between
      dietary and supplementary intake of the antioxidants vitamin C, vitamin E, and
      beta-carotene and sperm chromatin integrity. Eighty-seven healthy male volunteers
      donated semen samples, completed food-frequency questionnaires, and provided
      information about their sociodemographic characteristics, medical and
      reproductive histories, and lifestyle habits. Sperm chromatin integrity was
      measured using the DNA fragmentation index (DFI) and related parameters, obtained
      from the sperm chromatin structure assay (SCSA). SCSA measures the susceptibility
      of sperm DNA to acid-induced denaturation in situ. After adjusting for age and
      duration of abstinence, there was no dose-response association between any DFI
      outcome and any antioxidant intake measure. Non-dose-related associations were
      found between beta-carotene intake and both the standard deviation of DFI (SD
      DFI) and the percent of immature sperm. Participants with moderate, but not high,
      beta-carotene intake had an increase in SD DFI compared with participants with
      low intake (adjusted means 206.7 and 180.5, respectively; P = .03), as well as an
      increase in the percentage of immature sperm (adjusted means 6.9% and 5.0%,
      respectively; P = .04). If antioxidant intake in the range studied is indeed
      beneficial for fertility in healthy men, it does not appear to be mediated
      through the integrity of sperm chromatin. The results of this study do not
      preclude possible beneficial effects of high antioxidant intake on sperm
      chromatin integrity for men with fertility problems.

PMID- 15955897
TI  - Capacitative calcium entry: a central role in hypoxic pulmonary vasoconstriction?

PMID- 15955898
TI  - Objective response rate as a surrogate end point: a commentary.

PMID- 15955899
TI  - Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily
      pretreated patients with locally advanced or metastatic breast cancer.
AB  - PURPOSE: In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of
      the mammalian target of rapamycin, were evaluated for efficacy, safety, and
      pharmacokinetics in patients with locally advanced or metastatic breast cancer
      who had been heavily pretreated. PATIENTS AND METHODS: Patients (n = 109) were
      randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute
      intravenous infusion. Patients were evaluated for tumor response, time to tumor
      progression, adverse events, and pharmacokinetics of temsirolimus. RESULTS:
      Temsirolimus produced an objective response rate of 9.2% (10 partial responses)
      in the intent-to-treat population. Median time to tumor progression was 12.0
      weeks. Efficacy was similar for both dose levels but toxicity was more common
      with the higher dose level, especially grade 3 or 4 depression (10% of patients
      at the 250-mg dose level, 0% at the 75-mg dose level). The most common
      temsirolimus-related adverse events of all grades were mucositis (70%),
      maculopapular rash (51%), and nausea (43%). The most common, clinically important
      grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia
      (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). CONCLUSION: In
      heavily pretreated patients with locally advanced or metastatic breast cancer, 75
      and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a
      generally tolerable safety profile.

PMID- 15955900
TI  - Phase I safety, pharmacokinetics, and clinical activity study of lapatinib
      (GW572016), a reversible dual inhibitor of epidermal growth factor receptor
      tyrosine kinases, in heavily pretreated patients with metastatic carcinomas.
AB  - PURPOSE: This study (EGF10004) assessed the safety/tolerability,
      pharmacokinetics, and clinical activity of daily oral dosing with lapatinib
      (GW572016) in patients with ErbB1-expressing and/or ErbB2-overexpressing advanced
      stage refractory solid tumors. PATIENTS AND METHODS: Heavily pretreated patients
      with ErbB1-expressing and/or ErbB2-overexpressing metastatic cancers were
      randomly assigned to one of five dose cohorts of lapatinib administered once
      daily. Pharmacokinetic samples were obtained on days 1 and 20. Clinical response
      was assessed every 8 weeks. RESULTS: Sixty-seven patients with metastatic solid
      tumors were treated with lapatinib. The most frequently reported drug-related
      adverse events were diarrhea (42%) and rash (31%). No grade 4 drug-related
      adverse events were reported. Five grade 3 drug-related toxicities
      (gastrointestinal events and rash) were experienced by four patients. Drug
      related interstitial pneumonitis or cardiac dysfunction associated with other
      ErbB-targeted therapies was not reported. Four patients with trastuzumab
      resistant metastatic breast cancer-two of whom were classified as having
      inflammatory breast cancer-had partial responses (PRs). Twenty-four patients with
      various other carcinomas experienced stable disease, of whom 10 received
      lapatinib for > or = 6 months. The relationships between lapatinib dose or serum
      concentration and clinical response could not be adequately characterized due to
      the limited response data. The incidence of diarrhea increased with increasing
      dose, whereas the incidence of rash was not related to dose. CONCLUSION:
      Lapatinib was well tolerated at doses ranging from 500 to 1,600 mg once daily.
      Clinical activity was observed in heavily pretreated patients with ErbB1
      expressing and/or ErbB2-overexpressing metastatic cancers, including four PRs in
      patients with trastuzumab-resistant breast cancers and prolonged stable disease
      in 10 patients.

PMID- 15955901
TI  - Combination antibody therapy with epratuzumab and rituximab in relapsed or
      refractory non-Hodgkin's lymphoma.
AB  - PURPOSE: To explore the safety and therapeutic activity of combination anti-B
      cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL). PATIENTS AND
      METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22
      epratuzumab 360 mg/m(2) and anti-CD20 rituximab 375 mg/m(2) monoclonal antibodies
      weekly for four doses each. Sixteen patients had indolent histologies (15 with
      follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell
      lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to
      six) prior treatment, with 31% refractory to their last therapy and 81% with high
      risk Follicular Lymphoma International Prognostic Index scores. Patients with
      DLBCL had a median of three (range, one to eight) prior regimens (14% resistant
      to last treatment) and 71% had high intermediate-risk or high-risk International
      Prognostic Index scores. All patients were rituximab naive. RESULTS: Treatment
      was well tolerated, with toxicities principally infusion-related and
      predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an
      objective response (OR), including nine of 15 (60%) with complete responses (CRs
      and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved
      an OR, including three (50%) CRs. Median time to progression for all indolent NHL
      patients was 17.8 months. CONCLUSION: The full-dose combination of epratuzumab
      with rituximab was well tolerated and had significant clinical activity in NHL,
      suggesting that this combination should be tested in comparison with single-agent
      treatment.

PMID- 15955902
TI  - Report of an international workshop to standardize baseline evaluation and
      response criteria for primary CNS lymphoma.
AB  - Standardized guidelines for the baseline evaluation and response assessment of
      primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical
      trials for newly diagnosed patients. The relative rarity of this tumor precludes
      rapid completion of large-scale phase III trials and, therefore, our reliance on
      the results of well-designed phase II trials is critical. To formulate this
      recommendation, an international group of experts representing hematologic
      oncology, medical oncology, neuro-oncology, neurology, radiation oncology,
      neurosurgery, and ophthalmology met to review current standards of reporting and
      to formulate a consensus opinion regarding minimum baseline evaluation and common
      standards for assessing response to therapy. The response guidelines were based
      on the results of neuroimaging, corticosteroid use, ophthalmologic examination,
      and CSF cytology. A critical issue that requires additional study is the optimal
      method to assess the neurocognitive impact of therapy and address the quality of
      life of PCNSL survivors. We hope that these guidelines will improve communication
      among investigators and comparability among clinical trials in a way that will
      allow us to develop better therapies for patients.

PMID- 15955903
TI  - Avascular necrosis of femoral and/or humeral heads in multiple myeloma: results
      of a prospective study of patients treated with dexamethasone-based regimens and
      high-dose chemotherapy.
AB  - PURPOSE: To assess the prevalence, time of onset, risk factors, and outcome of
      avascular necrosis (AVN) of bone in patients with multiple myeloma undergoing
      antineoplastic therapy. PATIENTS AND METHODS: A total of 553 consecutive
      assessable patients were enrolled onto a treatment protocol consisting of
      dexamethasone-containing induction chemotherapy, autologous stem-cell
      transplantation, consolidation chemotherapy, and maintenance with interferon
      alfa. Patients were randomly assigned to receive thalidomide (269 patients) or no
      thalidomide (284 patients) throughout the study period. RESULTS: With a median
      follow-up of 33 months (range, 5 to 114 months), AVN of the femoral head(s)
      developed in 49 patients (9%). Median time to onset of AVN was 12 months (range,
      2 to 41 months). Three risk factors for AVN were identified by multivariate
      analysis: cumulative dexamethasone dose (odds ratio [OR], 1.028; 95% CI, 1.012 to
      1.044; P = .0006 [per 40 mg dexamethasone]), male sex (OR, 0.390; 95% CI, 0.192
      to 0.790; P = .009), and younger age (OR, 0.961; 95% CI, 0.934 to 0.991 per year;
      P = .0122). Thalidomide-treated patients had a prevalence of AVN similar to that
      of the control group (8% v 10%, respectively; P = .58). AVN-related pain and
      limited range of motion of the affected joint were present in only nine and four
      patients, respectively, and four patients underwent hip replacement because of
      AVN. Fluorine-18 fluorodeoxyglucose positron emission tomography failed to detect
      abnormal uptake in the AVN-affected bones. CONCLUSION: AVN is a rare and usually
      asymptomatic complication during myeloma therapy. Cumulative dexamethasone dose,
      male sex, and younger age, but not thalidomide, increase the risk of AVN.

PMID- 15955904
TI  - Hodgkin's lymphoma in elderly patients: a comprehensive retrospective analysis
      from the German Hodgkin's Study Group.
AB  - PURPOSE: With improved prognosis for patients with Hodgkin's lymphoma (HL),
      interest increasingly focuses on high-risk groups such as elderly patients. We
      thus performed a retrospective analysis using the German Hodgkin's Study Group
      (GHSG) database to determine clinical risk factors, course of treatment, and
      outcome in elderly HL patients in comparison with younger adults. PATIENTS AND
      METHODS: A total of 4,251 patients included in the GHSG studies HD5 to HD9 were
      analyzed, of whom 372 (8.8%) were 60 years or older and 3,879 (91.2%) were
      younger than 60 years. Patient characteristics, treatment results, toxicity,
      freedom from treatment failure (FFTF), and overall survival (OS) were compared.
      RESULTS: Elderly patients more often had mixed cellularity subtype, "B" symptoms,
      elevated erythrocyte sedimentation rate, and poorer performance status. Less
      frequently observed were nodular sclerosis subtype, large mediastinal mass, and
      bulky disease. Acute toxicity during chemotherapy was generally higher in elderly
      patients. This was most obvious for severe infections (grade 3 or 4; 15% v 6%)
      correlating with more severe leukopenia in elderly patients (grade 4; 38% v 23%).
      As a result, significantly fewer elderly patients received the intended full
      chemotherapy dose (75% v 91%). The survival analysis showed a significantly
      poorer treatment outcome for elderly patients in terms of 5-year OS (65% v 90%),
      FFTF (60% v 80%), and HL-specific FFTF (73% v 82%). CONCLUSION: Elderly patients
      have a poorer risk profile compared with younger HL patients and experience more
      severe treatment-associated toxicity. Higher mortality during treatment as well
      as lower dose-intensity are the major factors explaining the poorer overall
      outcome of elderly HL patients.

PMID- 15955905
TI  - Introduction of combined CHOP plus rituximab therapy dramatically improved
      outcome of diffuse large B-cell lymphoma in British Columbia.
AB  - PURPOSE: For more than two decades, cyclophosphamide, doxorubicin, vincristine,
      and prednisone (CHOP) has been the standard therapy for diffuse large B-cell
      lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve
      outcome in elderly patients with DLBCL. We conducted a population-based analysis
      to assess the impact of this combination therapy on adult patients with DLBCL in
      the province of British Columbia (BC). METHODS: We compared outcomes during a 3
      year period; 18 months before (prerituximab) and 18 months after (postrituximab)
      institution of a policy recommending the combination of CHOP and rituximab for
      all patients with newly diagnosed advanced-stage (stage III or IV or stage I or
      II with "B" symptoms or bulky [> 10 cm] disease) DLBCL. RESULTS: A total of 292
      patients were evaluated; 140 in the prerituximab group (median follow-up, 42
      months) and 152 in the postrituximab group (median follow-up, 24 months). Both
      progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and
      overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were
      significantly improved in the postrituximab group. After controlling for age and
      International Prognostic Index score, era of treatment remained a strong
      independent predictor of progression-free survival (risk ratio, 0.59; 95% CI,
      0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to
      0.66; P < .001). The benefit of treatment in the postrituximab era was present
      regardless of age. CONCLUSION: The addition of rituximab to CHOP chemotherapy has
      resulted in a dramatic improvement in outcome for DLBCL patients of all ages in
      the province of BC.

PMID- 15955908
TI  - ASPB's response to the NIH's Public Access Policy.

PMID- 15955906
TI  - Objective response to chemotherapy as a potential surrogate end point of survival
      in metastatic breast cancer patients.
AB  - PURPOSE: To assess the validity of objective response to chemotherapy as a
      surrogate end point for survival in metastatic breast cancer. PATIENTS AND
      METHODS: We carried out a meta-analysis on individual data from 2,126 metastatic
      breast cancer patients who were enrolled onto 10 randomized trials comparing
      standard versus intensified epirubicin-containing chemotherapy. RESULTS: The
      intensified chemotherapy was associated with a significantly higher tumor
      response rate compared with standard chemotherapy (pooled odds ratio for
      nonresponse, 0.60; 95% CI, 0.51 to 0.72). The intensified regimens also led to
      better (although not significant) survival (pooled odds ratio, 0.94; 95% CI, 0.86
      to 1.04; P = .22). Tumor response was a highly significant predictor of survival
      (P < .0001). When tumor response was introduced in the Cox model, the hazard
      ratio in favor of experimental treatment changed from 0.94 to 1.005 (95% CI, 0.91
      to 1.11; P = .92), indicating that no residual effect of the experimental
      treatment on survival was present once tumor response was adjusted for. This
      suggests that the overall survival benefit of intensified epirubicin was a result
      of the increase in response rate. The median survival time of patients with
      complete response and partial response was 28.8 months (95% CI, 25.4 to 45.3
      months) and 21.3 months (95% CI, 19.2 to 22.4 months), respectively; whereas, the
      median survival time of patients with no response was 14.6 months (95% CI, 13.9
      to 15.4 months). CONCLUSION: These results support the hypothesis that the
      achievement of an objective response to chemotherapy in metastatic breast cancer
      is associated with a true survival benefit. The potential role of objective
      response as a surrogate end point for survival in chemotherapy trials of
      metastatic breast cancer warrants further investigation.

PMID- 15955909
TI  - Genetic networks.

PMID- 15955910
TI  - Comparative plant genomics. Frontiers and prospects.

PMID- 15955911
TI  - Developmental networks.

PMID- 15955912
TI  - Systems biology for the virtual plant.

PMID- 15955913
TI  - Genetically encoded FRET sensors for visualizing metabolites with subcellular
      resolution in living cells.

PMID- 15955914
TI  - Dude, where's my phenotype? Dealing with redundancy in signaling networks.

PMID- 15955915
TI  - Prospects and challenges in proteomics.

PMID- 15955916
TI  - Adding precision tools to the plant biologists' toolbox with chemical genomics.

PMID- 15955917
TI  - Small RNAs and Arabidopsis. A fast forward look.

PMID- 15955918
TI  - Natural variation in Arabidopsis. How do we find the causal genes?

PMID- 15955919
TI  - Bioinformatics. Current limitations and insights for the future.

PMID- 15955920
TI  - ChemMine. A compound mining database for chemical genomics.

PMID- 15955921
TI  - Evolutionary and ecological genomics of Arabidopsis.

PMID- 15955922
TI  - High-throughput RNA isolation technologies. New tools for high-resolution gene
      expression profiling in plant systems.

PMID- 15955923
TI  - Update on proteomics in Arabidopsis. Where do we go from here?

PMID- 15955924
TI  - Genome organization of more than 300 defensin-like genes in Arabidopsis.
AB  - Defensins represent an ancient and diverse set of small, cysteine-rich,
      antimicrobial peptides in mammals, insects, and plants. According to published
      accounts, most species' genomes contain 15 to 50 defensins. Starting with a set
      of largely nodule-specific defensin-like sequences (DEFLs) from the model legume
      Medicago truncatula, we built motif models to search the near-complete
      Arabidopsis (Arabidopsis thaliana) genome. We identified 317 DEFLs, yet 80% were
      unannotated at The Arabidopsis Information Resource and had no prior evidence of
      expression. We demonstrate that many of these DEFL genes are clustered in the
      Arabidopsis genome and that individual clusters have evolved from successive
      rounds of gene duplication and divergent or purifying selection. Sequencing
      reverse transcription-PCR products from five DEFL clusters confirmed our gene
      predictions and verified expression. For four of the largest clusters of DEFLs,
      we present the first evidence of expression, most frequently in floral tissues.
      To determine the abundance of DEFLs in other plant families, we used our motif
      models to search The Institute for Genomic Research's gene indices and identified
      approximately 1,100 DEFLs. These expressed DEFLs were found mostly in
      reproductive tissues, consistent with our reverse transcription-PCR results.
      Sequence-based clustering of all identified DEFLs revealed separate tissue- or
      taxon-specific subgroups. Previously, we and others showed that more than 300
      DEFL genes were expressed in M. truncatula nodules, organs not present in most
      plants. We have used this information to annotate the Arabidopsis genome and now
      provide evidence of a large DEFL superfamily present in expressed tissues of all
      sequenced plants.

PMID- 15955925
TI  - Phylogenomic analysis of the receptor-like proteins of rice and Arabidopsis.
AB  - The tomato (Lycopersicon esculentum) Cf-9 resistance gene encodes the first
      characterized member of the plant receptor-like protein (RLP) family. Other RLPs
      such as CLAVATA2 and TOO MANY MOUTHS are known to regulate development. The
      domain structure of RLPs consists of extracellular leucine-rich repeats, a
      transmembrane helix, and a short cytoplasmic region. Here, we identify 90 RLPs in
      rice (Oryza sativa) and compare them with functionally characterized RLPs from
      different plant species and with 56 Arabidopsis (Arabidopsis thaliana) RLPs,
      including the downy mildew resistance protein RPP27. Many RLPs cluster into four
      distinct superclades, three of which include RLPs known to be involved in plant
      defense. Sequence comparisons reveal diagnostic amino acid residues that may
      specify different molecular functions in different RLP subtypes. This analysis of
      rice RLPs thus identified at least 73 candidate resistance genes and four genes
      potentially involved in development. Due to the synteny between rice and other
      Gramineae, this analysis should provide valuable tools for experimental studies
      in rice and other cereals.

PMID- 15955927
TI  - Maturation of the ground tissue of the root is regulated by gibberellin and
      SCARECROW and requires SHORT-ROOT.

PMID- 15955926
TI  - Immunopurification of polyribosomal complexes of Arabidopsis for global analysis
      of gene expression.
AB  - Immunoaffinity purification of polyribosomes (polysomes) from crude leaf extracts
      of Arabidopsis (Arabidopsis thaliana) was achieved with transgenic genotypes that
      overexpress a translational fusion of a ribosomal protein (RP) with a His(6)-FLAG
      dual epitope tag. In plants with a cauliflower mosaic virus 35S:HF-RPL18
      transgene immunopurification with anti-FLAG agarose beads yielded 60-Svedberg
      ribosomal subunits, intact 80-Svedberg monosomes and polysomes. Sucrose density
      gradient fractionation of the purified complexes demonstrated that the
      distribution of polysome size was similar in crude cell extracts and the purified
      complexes. The immunopurified complexes included putative cytosolic RPs of
      Arabidopsis and ribosome-associated proteins, as well as full-length transcripts
      of high and low abundance. Whole-genome profiling using long DNA oligonucleotide
      based microarrays provided a high level of reproducibility between polysomal mRNA
      samples immunopurified from two independent biological replicates (r
      approximately 0.90). Comparison of immunopurified and total cellular RNA samples
      revealed that for most of the genes, the mRNAs were associated with the epitope
      tagged polysomal complexes, with an average relative level of association of
      62.06% +/- 4.39%. The results demonstrate that the immunopurification of
      polysomes can be a valuable tool for the quantification of mRNAs present in
      translation complexes in plant cells. This technology can be extended to
      evaluation of mRNA populations at the cell- or tissue-specific level by
      regulation of the tagged RP with distinct promoters.

PMID- 15955929
TI  - Leukoaraiosis: the brain under pressure: target for treatment?

PMID- 15955930
TI  - Antiepileptic drugs for the elderly: using the old to focus on the new.

PMID- 15955931
TI  - Diagnostic criteria for schwannomatosis.
AB  - The neurofibromatoses are a diverse group of genetic conditions that share a
      predisposition to the development of tumors of the nerve sheath. Schwannomatosis
      is a recently recognized third major form of neurofibromatosis (NF) that causes
      multiple schwannomas without vestibular tumors diagnostic of NF2. Patients with
      schwannomatosis represent 2.4 to 5% of all patients requiring schwannoma
      resection and approximately one third of patients with schwannomatosis have
      anatomically localized disease with tumors limited to a single limb or segment of
      spine. Epidemiologic studies suggest that schwannomatosis is as common as NF2,
      but that familial occurrence is inexplicably rare. Patients with schwannomatosis
      overwhelmingly present with pain, and pain remains the primary clinical problem
      and indication for surgery. Diagnostic criteria for schwannomatosis are needed
      for both clinicians and researchers, but final diagnostic certainly will await
      the identification of the schwannomatosis locus itself.

PMID- 15955932
TI  - Ambulatory blood pressure and the brain: a 5-year follow-up.
AB  - OBJECTIVE: To determine if initial values of casual and ambulatory systolic blood
      pressure (SBP) predict white matter hyperintensities, insular subcortex
      hyperintensities, and brain atrophy 5 years later in a group of healthy elderly
      individuals. METHODS: The authors studied 155 healthy men and women, aged 55 to
      79 years. Two 24-hour ambulatory blood pressure (BP) sessions assessed BP level
      and variability during waking and sleep. Hyperintensities and total brain volume
      were quantified by MRI. Procedures were repeated 5 years later in 78% (121) of
      subjects. RESULTS: Hyperintensities and brain atrophy increased over time, with
      greater increases among older subjects. The presence of increased BP level and
      variability initially and again 5 years later had negative consequences for the
      brain. Independent of age, the greater the initial SBP, the greater the
      likelihood that individuals would have severe white matter hyperintensities after
      5 years. Also, elevated casual SBP was associated with severe insular subcortex
      hyperintensities and greater SBP sleep variability with increased brain atrophy.
      CONCLUSIONS: Among healthy elderly individuals whose initial, average, casual
      blood pressure (BP) was relatively low (116.9/71.1 mm Hg), small increases in
      casual and 24-hour ambulatory BP measures were associated with greater brain
      atrophy and subcortical lesions after 5 years.

PMID- 15955933
TI  - Neuropsychological tests accurately predict incident Alzheimer disease after 5
      and 10 years.
AB  - OBJECTIVE: To determine whether neuropsychological tests accurately predict
      incident Alzheimer disease (AD) after 5 and 10 years in participants of the
      Canadian Study of Health and Aging (CSHA) who were initially nondemented.
      METHODS: The CSHA was conducted in three waves: CSHA-1 (1991 to 1992), CSHA-2
      (1996 to 1997), and CSHA-3 (2001 to 2002). The 10-year prediction study included
      those who completed neuropsychological testing at CSHA-1 and received a
      diagnostic assessment at CSHA-3 (n = 263). The 5-year prediction study included
      those who completed neuropsychological testing at CSHA-2 and received a
      diagnostic assessment at CSHA-3 (n = 551). The diagnostic workup for dementia at
      CSHA-3 was formulated without knowledge of neuropsychological test performance at
      CSHA-1 or CSHA-2. The authors excluded cases with a baseline diagnosis of
      dementia or a prior history of any condition likely to affect the brain. Age and
      education were included in all analyses as covariates. RESULTS: In the 10-year
      follow-up study, only one test (short delayed verbal recall) emerged from the
      forward regression analyses. The model with this test and two covariates was
      significant, chi2 (3) = 31.61, p < 0.0001 (sensitivity = 73%, specificity = 70%).
      In the 5-year follow-up study, three tests (short delayed verbal recall, animal
      fluency, and information) emerged from the forward logistic regression analyses.
      The model was significant, chi2 (5) = 91.34, p < 0.0001 (sensitivity = 74%,
      specificity = 83%). Both models were supported with bootstrapping estimates.
      CONCLUSIONS: In a large epidemiologic sample of nondemented participants,
      neuropsychological tests accurately predicted conversion to Alzheimer disease
      after 5 and 10 years.

PMID- 15955934
TI  - Reduced hippocampal metabolism in MCI and AD: automated FDG-PET image analysis.
AB  - BACKGROUND: To facilitate image analysis, most recent 2-[18F]fluoro-2-deoxy-d
      glucose PET (FDG-PET) studies of glucose metabolism (MRglc) have used automated
      voxel-based analysis (VBA) procedures but paradoxically none reports hippocampus
      MRglc reductions in mild cognitive impairment (MCI) or Alzheimer disease (AD).
      Only a few studies, those using regions of interest (ROIs), report hippocampal
      reductions. The authors created an automated and anatomically valid mask
      technique to sample the hippocampus on PET (HipMask). METHODS: Hippocampal ROIs
      drawn on the MRI of 48 subjects (20 healthy elderly [NL], 16 MCI, and 12 AD) were
      used to develop the HipMask. The HipMask technique was applied in an FDG-PET
      study of NL (n = 11), MCI (n = 13), and AD (n = 12), and compared to both MRI
      guided ROIs and VBA methods. RESULTS: HipMask and ROI hippocampal sampling
      produced significant and equivalent MRglc reductions for contrasts between MCI
      and AD relative to NL. The VBA showed typical cortical effects but failed to show
      hippocampal MRglc reductions in either clinical group. Hippocampal MRglc was the
      only discriminator of NL vs MCI (78% accuracy) and added to the cortical MRglc in
      classifying NL vs AD and MCI vs AD. CONCLUSIONS: The new HipMask technique
      provides accurate and rapid assessment of the hippocampus on PET without the use
      of regions of interest. Hippocampal glucose metabolism reductions are found in
      both mild cognitive impairment and Alzheimer disease and contribute to their
      diagnostic classification. These results suggest re-examination of prior voxel
      based analysis 2-[18F]fluoro-2-deoxy-d-glucose PET studies that failed to report
      hippocampal effects.

PMID- 15955936
TI  - Antiepileptic drug use of women with epilepsy and congenital malformations in
      offspring.
AB  - OBJECTIVE: To compare the risk for congenital malformations in offspring between
      women with epilepsy being treated with antiepileptic drugs (AEDs) during
      pregnancy and those who discontinued their antiepileptic medication before
      pregnancy in a population-based cohort of female patients with epilepsy. METHODS:
      All patients with epilepsy (n = 20,101) eligible for AED reimbursement for the
      first time during 1985 to 1994 were identified from the Social Insurance
      Institution of Finland. Information on births during 1991 to 2000 was obtained
      from the National Medical Birth Registry. Information on AED use during pregnancy
      and on pregnancy outcomes was abstracted from medical records. RESULTS:
      Congenital malformations were more common among offspring of women on
      antiepileptic medication (65/1,411; 4.6%) than among offspring of untreated
      patients (26/939; 2.8%) (p = 0.02). The risk of malformations was substantially
      higher in the offspring of patients using valproate as monotherapy (OR = 4.18;
      95% CI: 2.31, 7.57) or valproate as polytherapy (OR = 3.54; 95% CI: 1.42, 8.11)
      than of untreated patients. Polytherapy without valproate was not associated with
      increased risk of malformations. CONCLUSION: Excess risk was confined to patients
      using valproate during pregnancy. The risk for malformations was not elevated in
      offspring of mothers using carbamazepine, oxcarbazepine, or phenytoin (as
      monotherapy or polytherapy without valproate).

PMID- 15955935
TI  - New onset geriatric epilepsy: a randomized study of gabapentin, lamotrigine, and
      carbamazepine.
AB  - OBJECTIVE: To determine the relative tolerability and efficacy of two newer
      antiepileptic drugs, lamotrigine (LTG) and gabapentin (GBP), as compared to
      carbamazepine (CBZ) in older patients with epilepsy. METHODS: This was an 18
      center, randomized, double-blind, double dummy, parallel study of 593 elderly
      subjects with newly diagnosed seizures. Patients were randomly assigned to one of
      three treatment groups: GBP 1,500 mg/day, LTG 150 mg/day, CBZ 600 mg/day. The
      primary outcome measure was retention in trial for 12 months. RESULTS: Mean age
      was 72 years. The most common etiology was cerebral infarction. Patients had
      multiple medical conditions and took an average of seven comedications. Mean
      plasma levels at 6 weeks were as follows: GBP 8.67 +/- 4.83 microg/mL, LTG 2.87
      +/- 1.60 microg/mL, CBZ 6.79 +/- 2.92 microg/mL. They remained stable throughout
      the trial. Early terminations: LTG 44.2%, GBP 51%, CBZ 64.5% (p = 0.0002).
      Significant paired comparisons: LTG vs CBZ: p < 0.0001; GBP vs CBZ: p = 0.008.
      Terminations for adverse events: LTG 12.1%, GBP 21.6%, CBZ 31% (p = 0.001).
      Significant paired comparisons: LTG vs CBZ: p < 0.0001; LTG vs GBP: p = 0.015.
      There were no significant differences in seizure free rate at 12 months.
      CONCLUSIONS: The main limiting factor in patient retention was adverse drug
      reactions. Patients taking lamotrigine (LTG) or gabapentin (GBP) did better than
      those taking carbamazepine. Seizure control was similar among groups. LTG and GBP
      should be considered as initial therapy for older patients with newly diagnosed
      seizures.

PMID- 15955937
TI  - Clinical and EEG features of patients with EEG wicket rhythms misdiagnosed with
      epilepsy.
AB  - BACKGROUND: EEG wicket rhythms are 6- to 11-Hz medium-to-high voltage bursts that
      are sometimes misidentified as epileptogenic activity. The authors determined the
      clinical and EEG features of patients with wicket rhythms who had been
      incorrectly diagnosed with epilepsy. METHODS: Electroencephalographers at an
      epilepsy center re-read EEGs for patients referred for epilepsy management and
      identified patients with wicket rhythms. On further evaluation, the majority
      (54%; 25/46) of these patients were found not to have epilepsy. The authors
      compared the clinical and EEG features for the 25 patients with wickets and
      nonepileptic episodes with those of age- and sex-matched patients with partial
      onset epilepsy using univariate and multivariate analysis. RESULTS: Several
      features distinguished patients with EEG wicket patterns and nonepileptic
      episodes (n = 25) from age- and sex-matched patients with epilepsy (n = 25): mid
      adult age at onset of episodes (mean 38.4 years vs 19.8 years), prolonged
      clinical episodes (mean 155 minutes vs 2.3 minutes), and long duration of EEG
      wicket patterns (mean 0.66 seconds vs 0.11 second spikes). After controlling for
      other factors, patients without major confusion during episodes were unlikely to
      have epilepsy. CONCLUSION: Wicket patterns are often interpreted as
      epileptogenic. This distinctive EEG pattern should be considered in patients with
      clinical episodes atypical for epilepsy.

PMID- 15955938
TI  - Gyratory seizures revisited: a video-EEG study.
AB  - PURPOSE: Gyratory seizures (GSs) have been rarely described in generalized as
      well as in focal epilepsies. They were defined as a rotation around the body axis
      during a seizure for at least 180 degrees. The mechanisms of generation are
      unknown and have been discussed controversially. The aim of this investigation
      was to further delineate seizure semiology and assess a possible lateralizing and
      localizing value of GSs. METHODS: The authors screened 277 consecutive patients
      with intractable epilepsies referred to a University Hospital for presurgical
      evaluation between 1998 and 2004 for GSs: 169 had temporal lobe epilepsy (TLE),
      47 frontal lobe epilepsy (FLE), 38 generalized epilepsies (GE), and 23 had
      extratemporal or multifocal epilepsy. RESULTS: Twelve patients showed gyratory
      movements in 17 seizures. Eight had FLE and four TLE (p < 0.001). In 58% (7/12),
      the gyratory movement was initiated by a forced versive movement of the head
      followed by a rotation toward the contralateral side of seizure onset. In 42%
      (5/12), the gyratory movement was not preceded by a forced head version. In these
      seizures, the direction of the rotation was toward the side of seizure onset.
      CONCLUSIONS: The direction of rotation lateralizes seizure onset zone in focal
      epilepsy depending on the seizure evolution: 1) gyratory seizures (GSs) starting
      with a forced version of the head ensuing into a body rotation lateralize seizure
      onset zone contralateral to the direction of rotation. 2) In GSs without a
      preceding gyratory forced head version, the direction of rotation is toward the
      side of seizure onset. GSs occur more frequently in frontal lobe epilepsy than
      temporal lobe epilepsy, while none of our patients with GSs had generalized
      epilepsies.

PMID- 15955939
TI  - Social isolation and outcomes post stroke.
AB  - OBJECTIVE: To assess the relationship between social isolation and stroke
      outcomes in a multiethnic cohort. METHODS: As part of the Northern Manhattan
      Stroke Study, the authors prospectively followed a cohort of patients with stroke
      for 5 years. Baseline data including social isolation were collected. At follow
      up, the authors documented outcome events as defined by the first occurrence of
      myocardial infarction (MI), stroke recurrence, or death. Cox hazard models were
      used to calculate the hazard ratio (HR, 95% CI) for prestroke predictors of post
      stroke outcomes. RESULTS: The authors followed 655 ischemic stroke cases for a
      mean of 5 years. The cohort was 55% women; 17% white, 27% African American, 54%
      Hispanic; mean age 69 +/- 12 years. There were 265 first outcome events. In
      univariate analysis, coronary artery disease (OR 1.3, 1.0 to 1.7), age > 70 years
      (OR 1.9, 1.5 to 2.5), atrial fibrillation (AF) (OR 1.8, 1.3 to 2.5), race
      ethnicity (white vs Hispanic) (OR 1.7, 1.1 to 2.9), physical inactivity (OR 1.3,
      1.1 to 2.6), help at home (OR 1.8, 1.4 to 2.4), and social isolation (OR 1.4, 1.2
      to 1.6) were associated with increased risk of an outcome event. No association
      was seen for hypertension, diabetes, education, sex, insurance, occupation,
      marital status, or primary care physician. In the multivariable model controlling
      for age, AF (OR 1.9, 1.5 to 2.5), help at home (OR 1.5, 1.1 to 2.0), and social
      isolation (OR 1.4, 1.1 to 1.8) predicted outcome events. CONCLUSION: Prestroke
      social isolation is a predictor of outcome events post stroke. Lack of social
      support may contribute to poorer outcomes due to poor compliance, depression, and
      stress.

PMID- 15955940
TI  - Serum and CSF vitamin A concentrations in idiopathic intracranial hypertension.
AB  - BACKGROUND: Elevated serum retinol, CSF retinol, and serum retinol binding
      protein (RBP) levels have been found in some patients with idiopathic
      intracranial hypertension (IIH), but serum and CSF retinol levels have not been
      studied in matched serum and CSF samples in patients with IIH. OBJECTIVE: To
      determine whether serum and CSF vitamin A concentrations are associated with IIH.
      METHODS: The serum and CSF retinol concentrations were prospectively assessed in
      20 patients with IIH and 20 control subjects. RESULTS: CSF retinol concentration
      was higher in the patient group (median 575.91 nM) vs the control group (median
      63.35 nM) (p < 0.05). There was no difference in serum retinol levels between
      control subjects (median 896.51 nM) and patients (median 1,002.62 nM) (p = 0.10).
      There was an association between higher vitamin A levels (> 250 nM) and IIH (p =
      0.039). There was a correlation between CSF and serum retinol levels in patients
      (r = 0.82) and control subjects (r = 0.66). CONCLUSION: Elevated CSF retinol
      concentration is associated with idiopathic intracranial hypertension (IIH), but
      serum retinol level is not associated with IIH.

PMID- 15955941
TI  - Benign positional nystagmus: a study of its three-dimensional spatio-temporal
      characteristics.
AB  - OBJECTIVE: To describe the spatial and temporal characteristics of benign
      positional nystagmus (BPN) subtypes in benign positional vertigo (BPV) due to
      vestibular lithiasis affecting one or more semicircular canals (SCCs).
      BACKGROUND: Activation of SCC receptors by sequestered otoconia, either freely
      moving (canalithiasis) or cupula-adherent (cupulolithiasis) during head position
      changes with respect to gravity, is the accepted cause of BPV. Although accurate
      identification and interpretation of BPN is critical to BPV therapy, no rigorous,
      kinematically correct three-dimensional spatio-temporal analysis of BPN in all
      its forms exists. METHODS: Using dual-search scleral coils, the authors recorded
      BPN provoked by Dix-Hallpike or supine ear-down test in a two-axis whole-body
      rotator in 44 patients with refractory BPV. To localize the SCC affected, BPN
      rotation axes were compared to SCC axes, axes orthogonal to average SCC planes.
      RESULTS: Sixteen patients had upbeat, geotropic-torsional BPN in the Dix-Hallpike
      test to one side and five to both sides, with BPN rotation axes clustered around
      the lowermost posterior SCC axis. Seven had direction-changing horizontal BPN,
      three geotropic (canalithiasis) and four apogeotropic (cupulolithiasis), with
      rotation axes around the lowermost and uppermost horizontal SCC axis. Seven had
      predominantly downbeating BPN with rotation axes clustered around one superior
      SCC axis. Nine had upbeat, horizontal-torsional BPN with rotation axes located
      between posterior and horizontal SCC axes of the lowermost ear suggesting
      simultaneous lithiasis in both SCCs. BPN vector-guided repositioning therapy was
      successful in 43 patients. CONCLUSION: Benign positional vertigo can affect one
      or more semicircular canals and three-dimensional recording with vector analysis
      of the benign positional nystagmus (BPN) can guide canalith repositioning therapy
      especially in refractory cases with atypical BPN.

PMID- 15955942
TI  - Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson
      disease.
AB  - OBJECTIVE: To explore the impact of dopaminergic therapy on facilitatory premotor
      motor interactions in patients with Parkinson disease (PD). METHODS: Ten patients
      with PD and 10 age-matched healthy volunteers received repetitive transcranial
      magnetic stimulation (rTMS) over the left dorsal premotor cortex (5 Hz, 1,500
      stimuli, 90% of active motor threshold). Patients were studied while "on" and
      "off" medication. Motor evoked potentials (MEPs) were recorded from the right
      first dorsal interosseus muscle before and after rTMS to quantify changes in
      motor cortical excitability. The after-effects of rTMS on motor function were
      assessed using the Unified Parkinson's Disease Rating Scale and the kinematics of
      ballistic wrist flexions. RESULTS: MEPs evoked from the ipsilateral motor cortex
      were increased after premotor rTMS in relaxed normal subjects, consistent with an
      increase in motor cortex excitability. In patients with PD, the effect of
      premotor rTMS was modified by medication. When patients were in a practically
      defined "off" state, premotor rTMS had no effect on MEPs, whereas when they were
      in the "on" state, premotor rTMS facilitated MEPs. Premotor rTMS had no effect on
      clinical parkinsonian symptoms or motor performance of ballistic wrist movements,
      regardless of whether patients were in the "on" or "off" state. CONCLUSIONS: In
      Parkinson disease, the ability of premotor-motor connections to increase motor
      cortical excitability is defective but restored to normal by dopaminergic
      medication. Dopamine deficiency in the basal ganglia may affect the way that
      frontal motor areas interact with each other.

PMID- 15955943
TI  - Changes in cortical excitability with thalamic deep brain stimulation.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for several
      movement disorders. However, its mechanism of action is largely unknown. Both
      lesioning and DBS of the ventralis intermedius (VIM) nucleus of thalamus improve
      essential tremor. Although DBS was initially thought to inhibit the target
      neurons, recent studies suggest that DBS activates neurons. OBJECTIVE: To test
      the hypothesis that thalamic DBS activates the target area in patients with
      essential tremor. METHODS: Cortical excitability was assessed in seven
      unmedicated patients with essential tremor using unilateral stimulators implanted
      in the VIM of the dominant hemisphere and in 11 healthy controls using
      transcranial magnetic stimulation (TMS). Patients were studied during optimal DBS
      (ON condition), half the optimal frequency (HALF), and with DBS off (OFF) in
      random order. Tremor was assessed after a change in DBS setting. Electromyography
      was recorded from the dominant hand, and TMS was applied over the contralateral
      motor cortex using single and paired pulses to elicit motor evoked potentials
      (MEPs). MEP recruitment was determined using stimulus intensities from 100% to
      150% of motor threshold. RESULTS: Tremor scores were significantly improved with
      DBS ON. Analysis of variance showed a significant interaction between condition
      (ON, HALF, OFF, Normal) and stimulus intensity on MEP amplitude. During DBS ON
      MEP amplitudes were significantly higher compared with controls at high but not
      at low TMS intensities. CONCLUSION: Because the ventralis intermedius (VIM)
      projects directly to the motor cortex, the high motor evoked potential amplitude
      with deep brain stimulation ON suggests that VIM DBS activates rather than
      inhibits the target area.

PMID- 15955944
TI  - Restless legs syndrome: a community-based study of prevalence, severity, and risk
      factors.
AB  - OBJECTIVE: To assess the prevalence and severity of restless legs syndrome (RLS)
      in the general community and to investigate its potential relationship with iron
      metabolism and other potential risk factors. METHODS: This was a cross-sectional
      study of a sex- and age-stratified random sample of the general population (50 to
      89 years; n = 701). The diagnosis of RLS was established by face-to-face
      interviews; severity was graded on the RLS severity scale. Each subject underwent
      a thorough clinical examination and extensive laboratory testing. RESULTS: The
      prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients
      with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression.
      None had been previously diagnosed or was on dopaminergic therapy. Free serum
      iron, transferrin, and ferritin concentrations were similar in subjects with and
      without RLS. However, soluble transferrin receptor (sTR) concentrations were
      different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female
      sex and high sTR independently predicted the risk of RLS. CONCLUSION: This large
      survey confirms the high prevalence, female preponderance, and underrecognition
      of restless legs syndrome in the general community. Although two-thirds of
      patients had moderate to severe disease, none was on current dopaminergic
      therapy.

PMID- 15955945
TI  - Parkinson disease: handedness predicts asymmetry.
AB  - OBJECTIVE: To determine the proportion of individuals in a clinic-based setting
      that present with asymmetric Parkinson disease (PD) and identify predictive
      factors associated with asymmetric symptoms. METHODS: The authors examined right
      vs left difference scores on the Unified Parkinson Disease Rating Scale motor
      subscale in a consecutive clinical series of 1,277 individuals diagnosed with PD.
      Predictors of asymmetry included sex, symptomatic disease duration, age at onset,
      initial motor symptom laterality, handedness, and medical history variables
      (e.g., family history of PD). RESULTS: Nearly half the sample (46%) met criteria
      for asymmetric disease based on a right vs left difference score of > or =5
      points, and 12% of the sample had a difference score of > or =10 (difference
      score: mean = 4, SD = 3.4). All three cardinal features of PD showed
      characteristics of asymmetric disease presentation. Multiple regression analyses
      showed that an increased discrepancy between right- and left-sided symptoms was
      significantly associated with a shorter disease duration, younger age at
      symptomatic onset, asymmetric initial symptom onset, hand dominance, and a
      positive self-reported family history of "other" neurodegenerative disorder. Hand
      dominance was related to the side of asymmetric disease such that left-handed
      individuals tended to have more severe disease on the left side of the body.
      CONCLUSION: Asymmetric presentation of Parkinson disease features was a common
      occurrence in the clinical cohort. Asymmetry was reliably predicted by several
      clinical characteristics, although the moderate level of explained variance
      (i.e., between 16 and 23%) highlighted the need for additional research examining
      predictive models of asymmetric disease. Recommendations for the classification
      and measurement of asymmetric disease are discussed.

PMID- 15955946
TI  - Detection of common and private mutations in the COL6A1 gene of patients with
      Bethlem myopathy.
AB  - BACKGROUND: Dominant mutations in COL6A1, COL6A2, and COL6A3, the three genes
      encoding collagen type VI, a ubiquitous extracellular matrix protein, are
      associated with Bethlem myopathy (BM) and Ullrich scleroatonic muscular
      dystrophy. METHODS: The authors devised a method to screen the entire coding
      sequence of the three genes by reverse transcriptase-PCR amplification of total
      RNA from skin fibroblasts and direct sequencing of the resulting 25 overlapping
      cDNA fragments covering 107 exons. RESULTS: Four splicing and four missense
      mutations were identified in 16 patients with BM, six of which are novel
      mutations in COL6A1. Both common and private mutations are localized in the
      alpha1 (VI) chain between the regions corresponding to the 3' end of the NH2
      globular domain and the 5' end of the triple helix, encoded by exons 3 through
      14. CONCLUSIONS: The clustering of the mutations in a relatively narrow area of
      the three collagen type VI chains in patients with Bethlem myopathy (BM) suggests
      that mutations in different regions could result in different phenotypes or in no
      phenotype at all. Moreover, the detection of mutations in only 60% of the
      patients suggests the existence of at least another gene associated with BM. The
      authors propose the direct sequencing of COL6 cDNAs as the first mutation
      screening analysis in BM, given the high number of exon-skipping events.

PMID- 15955947
TI  - The first organ transplant from a brain-dead donor.
AB  - In 1968, publication of the Harvard committee's report concerning "irreversible
      coma" established a paradigm for defining death by neurologic criteria (brain
      death [BD]). Five years earlier, Dr. Guy Alexandre, a Belgian surgeon, had not
      only adopted closely similar diagnostic criteria for BD but also applied those
      criteria in performing the first organ transplant from a brain-dead donor--a
      procedure many of his colleagues considered ethically unacceptable. To put those
      events into present-day perspective, the author reviewed the proceedings of a
      Ciba Symposium held in London in 1966 at which Alexandre introduced his
      pioneering view, obtaining information and documents from Alexandre and others
      who attended that meeting. Comparing Alexandre's approach with the Harvard report
      and later advances helps in understanding how both defining death by brain
      criteria and transplanting organs from a brain-dead donor have become morally
      tolerable today.

PMID- 15955948
TI  - Plexiform neurofibromas of the brachial plexuses.

PMID- 15955949
TI  - High titers of CA-125 may be associated with recurrent ischemic strokes in
      patients with cancer.
AB  - In addition to etiologies common in the general population, strokes in cancer
      patients may be caused by hypercoagulable states, hyperviscosity, cardiogenic
      embolism, and neoplastic vessel infiltration. Intravascular mucins were reported
      in patients with recurrent thromboembolism. The authors report four patients with
      metastatic cancer, brain infarcts, and other thromboembolic disease with markedly
      elevated levels of the tumor marker CA-125 and explore possible associations
      between this mucinous protein and strokes.

PMID- 15955950
TI  - TENS for the treatment of writer's cramp dystonia: a randomized, placebo
      controlled study.
AB  - Manipulation of afferent inputs may temporarily modulate dystonic spasms. Ten
      patients with writer's cramp were enrolled in a double-blind, randomized,
      crossover study in which the effects of transcutaneous electrical stimulation
      (TENS) and placebo treatment were compared. Patients were evaluated using four
      measures of dystonic impairment. The TENS group showed a significant improvement
      that persisted for 3 weeks in three of the four measures.

PMID- 15955951
TI  - A new botulinum toxin type A free of complexing proteins for treatment of
      cervical dystonia.
AB  - A new botulinum toxin type A free of complexing proteins (NT 201) was compared
      with BOTOX in patients with cervical dystonia by means of a double-blind
      noninferiority trial. Four hundred sixty-three patients received IM injections of
      70 to 300 U of NT 201 or BOTOX and were followed up over 16 weeks. The study
      clearly shows that NT 201 is at least as effective and safe as BOTOX.

PMID- 15955952
TI  - A novel TITF-1 mutation causes benign hereditary chorea with response to
      levodopa.
AB  - Presented is a pedigree with infancy-onset benign hereditary chorea (BHC) caused
      by a novel nonsense mutation in exon 3 (523G-->T, E175X) of the TITF-1 (Nkx2.1)
      gene. Four confirmed mutation carriers showed the typical movement disorder of
      BHC and congenital hypothyroidism. Surprisingly, treatment with levodopa improved
      gait dramatically and reduced chorea in two patients. Dopaminergic drugs should
      be considered a useful therapeutic option in BHC.

PMID- 15955953
TI  - Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset
      parkinsonism.
AB  - The authors performed PINK1 mutation analysis of 51 families with autosomal
      recessive Parkinson disease (ARPD). They found two novel PINK1 mutations: one was
      a homozygous deletion (13516-18118del) and the other a homozygous missense
      mutation (C388R). Clinically, the patients with the deletion had dementia. Thus,
      early-onset PD with dementia may be considered PINK1-linked parkinsonism.
      Furthermore, patients with PINK1 mutations form 8.9% of parkin- and DJ-1-negative
      ARPD families.

PMID- 15955954
TI  - The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease.
AB  - Mutations in the PINK1 gene cause autosomal recessive parkinsonism characterized
      by early onset and a variable phenotypic presentation. A patient homozygous for
      the Ala168Pro mutation has been fully characterized clinically. Apart from onset
      at age 39 years and the excellent and sustained response to levodopa, all
      clinical and laboratory features, including SPECT and assessment of autonomic
      function, were indistinguishable from typical idiopathic Parkinson disease.

PMID- 15955955
TI  - A neuropsychological assessment of phobias in patients with stiff person
      syndrome.
AB  - A neuropsychological assessment was performed in 10 patients with stiff person
      syndrome (SPS) to determine whether their anxiety and phobic symptoms precede
      stiffness and spasms or represent a reaction to disability. No neurocognitive
      dysfunction was noted. Patients perceived fears and anxiety as realistic and
      caused by SPS rather than due to an inherent phobic neurosis.

PMID- 15955956
TI  - A novel locus for X-linked recessive CMT with deafness and optic neuropathy maps
      to Xq21.32-q24.
AB  - The authors describe a Korean family with X-linked recessive Charcot-Marie-Tooth
      disease (CMT) having deafness and optic neuropathy. An X chromosome-wide linkage
      analysis identified a 15.2-cM candidate region flanked by DXS990 and DXS8067 on
      Xq21.32-q24 with the maximum lod score at DXS8077 (3.62, theta = 0.00). This
      locus does not overlap previously identified four loci for X-linked CMT, and the
      authors propose it as CMTX5.

PMID- 15955957
TI  - Quantitative myasthenia gravis score: assessment of responsiveness and
      longitudinal validity.
AB  - We prospectively tested the quantitative myasthenia gravis score (QMG) for
      responsiveness and longitudinal construct validity in 53 patients with myasthenia
      gravis. Index of responsiveness was high. Longitudinal construct validity was
      confirmed by the correlation between changes in QMG and manual muscle testing and
      by a difference in QMG changes across patients that were clinically unchanged,
      improved, or worse between two visits. Our results support QMG use for assessing
      clinical change in trials.

PMID- 15955958
TI  - Reversible impaired memory induced by pulsed methylprednisolone in patients with
      MS.
AB  - Thirty patients with multiple sclerosis were randomized to 500 or 2,000 mg of
      methylprednisolone (MP) over 5 days. They were prospectively studied
      neuropsychologically before and at days 6 and 60 after onset of the therapy,
      using a double-blind study design. Patients showed selective deterioration of
      declarative memory retrieval at day 6, which was fully reversible at day 60.
      Although the sample size was small, these effects were independent of the
      administered MP dose.

PMID- 15955959
TI  - Prognosis 30 years after temporal lobectomy.
AB  - To assess the long-term outcome after temporal lobectomy, the authors obtained
      information from 48 patients and families traced though the NIH Medical Records
      Department, Social Security, National Death Indices, and other sources.
      Preoperative evaluation, limited by current standards, was based mainly on
      interictal surface EEG. After a mean 29.9-year follow-up, 24 were seizure free,
      and 10 had died. Early seizure recurrence and invasive EEG studies predicted
      worse long-term outcome.

PMID- 15955960
TI  - Postictal neurogenic stunned myocardium.
AB  - Neurogenic left ventricular dysfunction is a recognized complication of
      subarachnoid hemorrhage, but this condition has not been reported after seizure
      activity. The authors present two cases of neurogenic stunned myocardium after
      convulsive seizures, suggesting that ictal activity can lead to sympathetically
      mediated cardiac injury.

PMID- 15955961
TI  - Induced hypertension improves cerebral blood flow in acute ischemic stroke.

PMID- 15955962
TI  - Sea wave-induced internal carotid artery dissection.

PMID- 15955963
TI  - Pseudo-ulnar sensory loss in a patient from a small cortical infarct of the
      postcentral knob.

PMID- 15955964
TI  - Seizures following reduction in phenytoin level after orally administered folic
      acid.

PMID- 15955965
TI  - Familial polyneuropathy with anti-myelin-associated glycoprotein antibodies.

PMID- 15955966
TI  - Hemiplegic ALS: Mills syndrome.

PMID- 15955967
TI  - Fiction: no laughing matter.

PMID- 15955968
TI  - Oral antispastic drugs in nonprogressive neurologic diseases: a systematic
      review.

PMID- 15955969
TI  - Association of genetic loci: replication or not, that is the question.

PMID- 15955970
TI  - Migraine and other headaches: associations with Rose angina and coronary heart
      disease.

PMID- 15955971
TI  - A 24-year follow-up of body mass index and cerebral atrophy.

PMID- 15955973
TI  - A focus on the synapse for neuroprotection in Alzheimer disease and other
      dementias.

PMID- 15955974
TI  - Clinical application of objective perimetry using multifocal visual evoked
      potentials in glaucoma practice.
AB  - OBJECTIVES: To evaluate the role of objective perimetry using multifocal visual
      evoked potentials (mVEPs) in glaucoma practice, and to assess its utility in
      patients with inconclusive standard automated perimetry findings. Method A
      retrospective case series of 436 consecutive subjects referred for glaucoma
      investigation who underwent testing with the AccuMap V1.3 mVEP system
      (ObjectiVision Pty, Ltd, Sydney, New South Wales, Australia) within a defined 12
      month period. Sensitivity was determined by comparing this testing with that of
      standard automated perimetry and that used in a subgroup in whom masked
      stereoscopic optic disc photographs were used as an alternative reference
      standard. Overall clinical diagnostic outcomes were assessed. RESULTS: The mVEP
      changes were correlated with the stage of disease and Humphrey mean deviation (r
      = 0.78). The overall sensitivity for detecting glaucoma with established
      subjective field loss was 97.5% (early glaucoma, 95.0%), whereas 92.2% of low
      risk suspects had normal mVEPs. When masked disc assessment alone was used for
      diagnosis of abnormality, sensitivity of mVEP (80.6%) and Humphrey visual field
      results (81.9%) were similar, but mVEP specificity was better (89.2% vs 79.5%).
      The mVEP was particularly useful in assessing excessive subjective field loss (45
      eyes) by showing a much closer correlation with the clinical picture.
      CONCLUSIONS: Multifocal VEP is an effective method for detecting visual field
      loss in glaucoma. It provides a valuable aid to the clinician in categorizing
      patients with unreliable, variable, unconfirmed, or excessive subjective field
      loss.

PMID- 15955975
TI  - Histologic, ultrastructural, and immunofluorescent evaluation of human laser
      assisted in situ keratomileusis corneal wounds.
AB  - OBJECTIVE: To evaluate human corneas after laser-assisted in situ keratomileusis
      at different postoperative intervals. METHODS: Thirty-eight postmortem corneas
      from 20 patients with postoperative intervals from 2 months to 6.5 years after
      laser-assisted in situ keratomileusis surgery were collected from eye banks. The
      corneas were trisected and processed for conventional histologic analysis,
      transmission electron microscopy, and immunofluorescence. RESULTS: Light
      microscopy and transmission electron microscopy showed focal undulations in
      Bowman layer, focal epithelial hypertrophic modifications, and a variably thick
      (range, 0.4-16.4-mum) lamellar stromal interface scar in all specimens. The flap
      wound margin, which was adjacent to the epithelium, healed by producing an
      approximately 8-mum-thick hypercellular fibrotic stromal scar, whereas the
      central and paracentral wound regions healed differently because a thinner
      (approximately 5-mum) hypocellular primitive stromal scar was present in all the
      corneas examined. Immunofluorescence identified increased type 3 collagen and
      myofibroblasts in the hypercellular fibrotic scar regions and decreased or absent
      levels of all corneal stromal components other than type 1 collagen in the
      hypocellular primitive scar regions. CONCLUSIONS: After laser-assisted in situ
      keratomileusis surgery, the keratocyte-mediated production of a variably thick
      lamellar corneal stromal scar occurs, resulting in 2 regional types of scarring.
      The hypercellular fibrotic scar at the wound margin is usually visible clinically
      and functions to hold the flap in place, while the more central hypocellular
      primitive scar is not visible clinically and allows easy lifting of the flap
      postoperatively.

PMID- 15955976
TI  - Computer classification of nonproliferative diabetic retinopathy.
AB  - OBJECTIVE: To propose methods for computer grading of the severity of 3 early
      lesions, namely, hemorrhages and microaneurysms, hard exudates, and cotton-wool
      spots, and classification of nonproliferative diabetic retinopathy (NPDR) based
      on these 3 types of lesions. METHODS: Using a computer diagnostic system
      developed earlier, the number of each of the 3 early lesions and the size of each
      lesion in the standard photographs were determined. Computer classification
      criteria were developed for the levels of individual lesions and for NPDR.
      Evaluation of the criteria was performed using 430 fundus images with normal
      retinas or any degree of retinopathy and 361 fundus images with no retinopathy or
      the 3 early lesions only. The results were compared with those of the graders at
      the University of Wisconsin Ocular Epidemiology Reading Center and an
      ophthalmologist. MAIN OUTCOME MEASURES: Agreement rates in the classification of
      NPDR between the computer system and human experts. RESULTS: In determining the
      severity levels of individual lesions, the agreement rates between the computer
      system and the reading center were 82.6%, 82.6%, and 88.3% using the 430 images
      and 85.3%, 87.5%, and 93.1% using the 361 images, respectively, for hemorrhages
      and microaneurysms, hard exudates, and cotton-wool spots. When the "questionable"
      category was excluded, the corresponding agreement rates were 86.5%, 92.3%, and
      91.0% using the 430 images and 89.7%, 96.3%, and 97.4% using the 361 images. In
      classifying NPDR, the agreement rates between the computer system and the
      ophthalmologist were 81.7% using the 430 images and 83.5% using the 361 images.
      CONCLUSIONS: The proposed criteria for computer classification produced results
      that are comparable with those provided by human experts. With additional
      research, this computer system could become a useful clinical aid to physicians
      and a tool for screening, diagnosing, and classifying NPDR.

PMID- 15955977
TI  - Macular retinoblastoma managed with chemoreduction: analysis of tumor control
      with or without adjuvant thermotherapy in 68 tumors.
AB  - OBJECTIVE: To evaluate the effectiveness of chemoreduction alone and
      chemoreduction with thermotherapy for macular retinoblastoma. DESIGN:
      Prospective, nonrandomized, single-center case series. SETTING: Ocular Oncology
      Service at Wills Eye Hospital of Thomas Jefferson University in conjunction with
      the Division of Oncology at the Children's Hospital of Philadelphia (Pa).
      PARTICIPANTS: There were 68 macular retinoblastomas in 62 eyes of 49 patients
      managed with chemoreduction from January 1995 through January 2003. Intervention
      All patients received 6 cycles of intravenous chemoreduction using vincristine,
      etoposide, and carboplatin. The patients were then treated according to 1 of 2
      approaches: chemoreduction alone with no adjuvant focal therapy (group A) or
      chemoreduction combined with adjuvant foveal-sparing thermotherapy to each
      macular retinoblastoma (group B). Main Outcome Measure Tumor recurrence. RESULTS:
      Of the 68 tumors, 28 were in group A and 40 were in group B. A comparison of both
      groups revealed that the tumors were similar with regard to clinical features.
      The mean tumor basal dimension was 12.3 mm for group A and 12.1 mm for group B,
      and the mean tumor thickness was 6.8 mm for group A and 6.1 mm for group B.
      Tumors in group A occupied a mean of 71% of the macula, and those in group B
      occupied 74% of the macula. Following treatment, Kaplan-Meier estimates revealed
      that group A tumors showed recurrence in 25% by 1 year and 35% by 4 years whereas
      those in group B showed recurrence in 17% by 1 year and 17% by 4 years. All
      recurrences were treated with additional focal thermotherapy, cryotherapy, or
      plaque radiotherapy except for 1 that required external beam radiotherapy and 1
      that required enucleation, both in group A. Univariate analysis revealed that
      predictors of tumor recurrence were intraretinal growth pattern (vs endophytic);
      small tumor basal dimension (less than 3 mm and occupying a smaller percentage of
      the macula); absence of subretinal fluid, subretinal seeds, and vitreous seeds;
      and chemoreduction response with less tumor calcification and tumor regression of
      type 0 (complete disappearance without a scar). By multivariate analysis, the
      most important factors predictive of tumor recurrence were smaller macular tumor
      size (judged by percentage of the macula occupied by the tumor), absence of
      subretinal or vitreous seeds, and unilateral disease. CONCLUSIONS: Treatment of
      macular retinoblastoma with chemoreduction plus adjuvant foveal-sparing
      thermotherapy provides tumor control of 83% by 4 years, and this is slightly more
      favorable than chemoreduction alone, which provides control of 65% by 4 years.
      Tumors most destined for recurrence are small tumors.

PMID- 15955978
TI  - Progression of age-related macular degeneration: prospective assessment of C
      reactive protein, interleukin 6, and other cardiovascular biomarkers.
AB  - BACKGROUND: Age-related macular degeneration (AMD) and cardiovascular disease
      share common risk factors. Inflammatory biomarkers, including C-reactive protein
      (CRP), interleukin 6 (IL-6), soluble tumor necrosis factor alpha receptor 2,
      soluble intercellular and vascular adhesion molecules (intercellular adhesion
      molecule 1 and vascular cell adhesion molecule 1), and lipid biomarkers,
      including lipoprotein(a) and apolipoprotein B, have all been associated with
      cardiovascular disease. We previously found an association between AMD and CRP in
      a cross-sectional analysis, but the prospective relationships between AMD, CRP,
      and the other cardiovascular disease markers are unknown. OBJECTIVE: To test the
      hypothesis that baseline cardiovascular disease biomarkers are associated with
      subsequent increased risk for progression of AMD. DESIGN, SETTING, AND
      PARTICIPANTS: This prospective cohort study involved 251 participants aged 60
      years and older who had some sign of nonexudative AMD and visual acuity of 20/200
      or better in at least one eye at baseline. The AMD status was assessed by
      standardized grading of fundus photographs, and stored fasting blood specimens
      obtained at baseline were analyzed for levels of the various biomarkers. The
      average follow-up time was 4.6 years. MAIN OUTCOME MEASURES: Relationship between
      biomarkers and incidence rates of progression of AMD. RESULTS: Comparing the
      highest quartile with the lowest quartile, CRP was associated with progression of
      AMD, with a multivariate adjusted relative risk (RR) of 2.10 (95% confidence
      interval [CI], 1.06-4.18; P for trend, .046) controlling for body mass index,
      smoking, and other cardiovascular variables and a multivariate adjusted RR of
      2.02 (95% CI, 1.00-4.04; P for trend, .06) controlling additionally for
      antioxidant nutrients. Interleukin 6 was also related to progression of AMD, with
      a multivariate adjusted RR of 1.81 (95% CI, 0.97-3.36; P for trend, .03).
      Comparing the highest quartile with the lowest quartile, the effect estimates for
      vascular cell adhesion molecule 1 (multivariate adjusted RR, 1.94) and
      apolipoprotein B (adjusted RR, 1.39) were in the positive direction but were not
      statistically significant (P for trend, .08 and .24, respectively). The CRP and
      IL-6 levels were both significantly related to higher body mass index and current
      smoking. CONCLUSIONS: Higher levels of the systemic inflammatory markers CRP and
      IL-6 are independently associated with progression of AMD.

PMID- 15955979
TI  - Delayed visual decline in patients with "stable" optic neuropathy.
AB  - BACKGROUND: Histological studies on the human optic nerve have documented
      decreasing axonal nerve fiber counts with age. In patients with optic atrophy, a
      nonpathological dropout of ganglion cell axons as part of the normal aging
      process may become clinically significant. OBJECTIVE: To describe the occurrence
      of delayed visual loss in patients with presumably "stable" optic neuropathy.
      METHODS: We reviewed the medical records of 3 patients who experienced slowly
      progressive visual loss in adulthood after suffering childhood optic nerve
      injury. RESULTS: All 3 patients had a monophasic illness in childhood that caused
      bilateral optic atrophy and visual impairment. Following decades of stability,
      each suffered a gradual, symptomatic visual decline that extended over years. No
      new ophthalmologic, systemic, or neurologic disorder was found that explained the
      visual decline in any of these patients. CONCLUSION: We hypothesize that the late
      visual decline in these 3 patients resulted from deleterious effects of age
      related axonal loss on an already depleted population of neurons.

PMID- 15955980
TI  - Blunt trauma of the aging eye: injury mechanisms and increasing lens stiffness.
AB  - OBJECTIVE: To investigate possible injury mechanisms in the eyes of elderly
      individuals and the effects of lens stiffness on model outputs indicative of
      injury as a function of age. METHODS: Three separate frontal impact scenarios, a
      foam particle (30 m/s), steering wheel (15 m/s), and air bag (67 m/s), were
      simulated with a validated finite-element model to determine the effects of
      changing lens stiffness on the eye when subjected to blunt trauma. The lens
      stiffness of the model was increased with increasing age using stiffness values
      determined from the literature for 3 age groups. RESULTS: The computational eye
      model demonstrated increasing peak stress in the posterior portion of the ciliary
      body and decreasing peak stress in the posterior portion of the zonules with
      increasing lens stiffness for the 2 most severe impact types, the air bag and
      steering wheel. Peak deformation of the lens decreased with increasing lens
      stiffness. CONCLUSIONS: On the basis of the computational modeling analysis, the
      risk of eye injury increases with age; as a result, the eyes of elderly patients
      may be more susceptible to ciliary body-related eye injuries in traumatic-impact
      situations. Clinical Relevance These data support the contention that trauma
      induced damage to the lens, ciliary body, and zonules may be related to increased
      stiffness of the lens. The data indicate that all people, especially elderly
      individuals, should use safety systems while driving an automobile and sit as far
      from the air bag as is comfortable. Those in sports or work environments
      requiring protective lenses should wear them. Designers of air bags and
      automobile companies should continue to work to reduce the potential that the air
      bag will contact the eye.

PMID- 15955981
TI  - Persistent fetal ocular vasculature in mice deficient in bax and bak.
AB  - BACKGROUND: The ocular fetal vasculature normally regresses by apoptosis but for
      unknown reasons fails to regress in the human disease persistent fetal
      vasculature. OBJECTIVE: To investigate whether proapoptotic Bcl-2 members, Bax
      and Bak, are involved in fetal vasculature regression. METHODS: Adult eyes from
      mice deficient in Bax and/or Bak were examined grossly and histologically for
      persistence of fetal vasculature. Vessels were identified by the presence of
      lumens and erythrocytes and by Factor VIII labeling. Eyes from postnatal day 7
      mice were processed for terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate nick-end labeling (TUNEL) analysis to determine if
      deficiency of Bax and Bak results in defective developmental apoptosis. RESULTS:
      Only bax(-/-)bak(-/-) eyes retained fetal vasculature into adulthood. This
      vasculature consisted of a hyaloid artery emerging from the optic nerve head and
      intravitreal and perilental vessels but not a pupillary membrane. At postnatal
      day 7, wild-type but not bax(-/-)bak(-/-) eyes had TUNEL-positive cells in the
      fetal vasculature. CONCLUSIONS: These data demonstrate that Bax and Bak serve
      overlapping functions in fetal vasculature regression, emphasizing the importance
      of apoptosis in developmental remodeling. Clinical Relevance Disruption of Bax
      and Bak results in persistent fetal vasculature in knockout mice, providing a
      model of the human disease persistent fetal vasculature to investigate its
      etiology and potential therapies.

PMID- 15955982
TI  - Age-related eye disease, quality of life, and functional activity.
AB  - OBJECTIVE: To examine the associations of measures of quality of life (Medical
      Outcomes Study Short Form Health Survey) and functional activities (activities of
      daily living, instrumental activities of daily living, and visual function) in
      persons with and without age-related eye diseases. METHODS: Two thousand, six
      hundred seventy persons participated in the 1998 through 2000 examinations of
      both the Beaver Dam Eye Study and the Epidemiology of Hearing Loss Study. Age
      related eye disease (age-related maculopathy, cataract, diabetic retinopathy,
      glaucoma, macula edema, occlusions, amblyopia, and macular holes) were assessed
      by fundus, slitlamp, and retroilluminated photographs and self-reported ocular
      history. Also administered was a standard interview that included the Medical
      Outcomes Study Short Form Health Survey, activities of daily living, instrumental
      activities of daily living, and visual function questionnaires and information on
      other medical conditions. RESULTS: After controlling for age and sex, we found
      that persons with an age-related eye disease had decreased scores in almost all
      the domains of the Medical Outcomes Study Short Form Health Survey, and persons
      with eye disease in both eyes had poorer scores than persons with eye disease in
      only 1 eye. Stratifying by age-related maculopathy and central cataract yielded
      similar results. Further adjustment for current visual acuity and the number of
      comorbid conditions explained most associations. Several of the mental scales
      were still marginally significantly lower (P<.10) in persons with age-related
      maculopathy after adjustment. Persons with an age-related eye disease were not
      more likely to have impaired activities of daily living or instrumental
      activities of daily living. After adjustment for current visual acuity and number
      of comorbidities, persons who had trouble reading small print or recognizing
      people across the street were more likely to have an age-related eye disease.
      Otherwise, there were no significant associations with the visual function
      questions and any of the specific ocular conditions. CONCLUSIONS: Many measures
      of general quality of life and functional activities were related to age-related
      eye diseases, but few associations remained significant after adjustments for
      vision and other comorbidities. Our data are compatible with the notion that
      decreased visual function, irrespective of the pathologic reason for the
      decrease, is associated with diminished quality of life and functional activities
      of living.

PMID- 15955983
TI  - Self-reported comorbidities and visual function in a population-based study: the
      Los Angeles Latino Eye Study.
AB  - OBJECTIVE: To assess the association of self-reported systemic and ocular
      comorbid disease and visual function in Latino subjects. METHODS: National Eye
      Institute 25-item Visual Function Questionnaire (NEI-VFQ-25) and eye examination
      data were obtained from 5380 participants in the Los Angeles Latino Eye Study, a
      population-based prevalence study of eye disease in Latino subjects 40 years and
      older. We developed and contrasted 5 comorbidity measures. One-way analysis of
      variance was used to assess the association between comorbidity and visual
      impairment and self-reported visual function. Regression analyses determined the
      association of sociodemographic variables, clinical variables, and the best
      measure of comorbidity with the NEI-VFQ-25 composite score. The main outcome
      measure was self-reported visual function as assessed by the NEI-VFQ-25 composite
      score. RESULTS: On average, visual function subscale scores were lowest for those
      participants with the most systemic comorbid conditions (P<.05). This was more
      evident in participants with moderate or severe visual impairment compared with
      those with mild or no visual impairment (P<.05). CONCLUSIONS: Self-reported
      systemic comorbidities were associated with self-reported visual function. This
      association was greater at more severe levels of visual impairment. Of the 5
      comorbidity measures assessed, the measure that summed the number of self
      reported systemic comorbidities correlated most with self-reported visual
      function.

PMID- 15955984
TI  - A population-based study on the visual outcome in 10-year-old preterm and full
      term children.
AB  - OBJECTIVES: To report the visual outcome in prematurely born and full-term
      children at the age of 10 years and to evaluate the effects of prematurity per
      se, retinopathy of prematurity (ROP), and cryotreatment on visual acuity.
      METHODS: The study included 216 prematurely born children and 217 children born
      at term from the same geographical area and study period. Best-corrected distance
      and near visual acuities were assessed with linear letter logarithm of the
      minimum angle of resolution charts. Crowding was evaluated. RESULTS: Prematurely
      born children had reduced distance and near visual acuities compared with full
      term children, even when children who had retinopathy of prematurity and
      neurologic disorders were excluded (P<.001). Children who had been treated with
      cryotherapy had the highest risk of a reduced visual acuity. Two percent of the
      prematurely born children were visually impaired (<20/60). CONCLUSIONS: Although
      we found an overall good visual outcome in the prematurely born cohort, the risk
      of reduced visual acuity was greater than in full-term children. Children who had
      been treated with cryotherapy had the highest risk, but prematurity per se was
      also associated with reduced visual acuity.

PMID- 15955985
TI  - Understanding eye trauma through computer modeling.

PMID- 15955986
TI  - Visuo-vestibular eye movements: infantile strabismus in 3 dimensions.
AB  - Infantile strabismus is accompanied by latent nystagmus, primary inferior oblique
      muscle overaction, and dissociated vertical divergence. If we examine the
      evolutionary underpinnings of these ocular rotations, we can construct a unifying
      mechanism for the sensorimotor abnormalities that arise in humans with infantile
      strabismus. Latent nystagmus, primary inferior oblique muscle overaction, and
      dissociated vertical divergence correspond to visual balancing reflexes that are
      operative in lateral-eyed animals in yaw, pitch, and roll, respectively. In
      humans with infantile strabismus, these subcortical visual reflexes are
      reactivated by a physiologic imbalance in binocular visual input, which resets
      central vestibular tone in 3-dimensional space. These visual reflexes reveal the
      evolutionary role of the eyes as sensory balance organs that can directly
      modulate central vestibular tone. Latent nystagmus, primary oblique muscle
      overaction, and dissociated vertical divergence should be reclassified as visuo
      vestibular eye movements.

PMID- 15955987
TI  - Ocular tuberculosis.

PMID- 15955988
TI  - Retinal metastasis presenting as a retinal hemorrhage in a patient with
      adenocarcinoma of the cecum.

PMID- 15955989
TI  - Late traumatic corneal wound dehiscence after penetrating keratoplasty.

PMID- 15955990
TI  - Aggressive retinal astrocytomas in 4 patients with tuberous sclerosis complex.

PMID- 15955991
TI  - Giant macular hole as an atypical consequence of a toxoplasmic chorioretinitis.

PMID- 15955992
TI  - Solitary choroidal tuberculoma in an immunocompetent patient.

PMID- 15955993
TI  - Multilobular choroidal melanoma following ruthenium 106 brachytherapy.

PMID- 15955995
TI  - Amyloid or asteroid?

PMID- 15955996
TI  - Koornneef's graded upper lid lengthening in Graves Disease.

PMID- 15955997
TI  - Ophthalmologists' referrals improve the lives of visually impaired patients.

PMID- 15955999
TI  - Screening for depression: this is the heart of the matter.

PMID- 15956000
TI  - Is proton pump inhibitor testing an effective approach to diagnose
      gastroesophageal reflux disease in patients with noncardiac chest pain?: a meta
      analysis.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) is common in patients with
      noncardiac chest pain (NCCP). Results of studies evaluating the accuracy of a
      proton pump inhibitor (PPI) treatment as a diagnostic test for GERD-related NCCP
      have varied. We evaluated the overall accuracy of this modality. METHODS: We
      searched the PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane databases to May 2004
      and included randomized, placebo-controlled studies evaluating the accuracy of
      findings from PPI testing in the diagnosis of GERD in patients with NCCP. The
      GERD diagnosis was confirmed by results of endoscopy and/or 24-hour esophageal pH
      monitoring. A summary diagnostic odds ratio and summary receiver operating
      characteristic curve analysis were used to estimate the overall accuracy and to
      explore any contributing factors. RESULTS: Six studies met the inclusion
      criteria. The overall sensitivity and specificity of a PPI test were 80% (95%
      confidence interval [CI], 71%-87%) and 74% (95% CI, 64%-83%), respectively,
      compared with 19% (95% CI, 12%-29%) and 77% (95% CI, 62%-87%), respectively, in
      the placebo group. The PPI test showed a significant higher discriminative power,
      with a summary diagnostic odds ratio of 19.35 (95% CI, 8.54-43.84) compared with
      0.61 (95% CI, 0.20-1.86) in the placebo group. The impact of the prevalence of
      GERD and treatment duration on the accuracy of the test could not be determined
      because of the lack of an adequate number of studies. CONCLUSION: The use of PPI
      treatment as a diagnostic test for detecting GERD in patients with NCCP has an
      acceptable sensitivity and specificity and could be used as an initial approach
      by primary care physicians to detect GERD in selected patients with NCCP.

PMID- 15956001
TI  - Coronary and aortic calcification in women with a history of major depression.
AB  - BACKGROUND: Although depression is a well-documented risk factor for clinical
      heart disease, its association with subclinical atherosclerosis is unclear. We
      hypothesized that middle-aged women with a history of recurrent major depression
      would show evidence of atherosclerosis. METHODS: Coronary and aortic
      calcification was measured by electron beam tomography in 58 African American and
      152 white healthy middle-aged women. Women were administered the Structured
      Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition and a self-report measure of current depressive symptoms. RESULTS:
      Coronary calcification was found in 103 women (49%) and aorta calcification in
      144 women (54%); high calcification scores were set at approximately 75% of the
      sample distribution (ie, at >/=10 for the coronary calcium score [n = 49 women]
      and at >100 for the aorta calcium score [n = 53 women]). Women with a history of
      recurrent major depression (n = 53) were more likely to have any coronary
      calcification or calcification in the high category at either site compared with
      women with a history of a single episode of depression or no depression. After
      stepwise forward adjustment for cardiovascular risk factors and sociodemographic
      characteristics, a history of recurrent major depression, compared with a single
      episode or no history, was associated with odds ratios (ORs) of 2.46 (95%
      confidence interval [CI], 1.06-5.67) for any coronary calcification, 2.71 (95%
      CI, 1.08-6.81) for high coronary calcification, and 3.39 (95% CI, 1.34-8.63) for
      high aortic calcification. Further adjustments for waist-hip ratio reduced the
      association between history of recurrent depression and any calcification (OR,
      2.24; 95% CI, 0.94-5.32) and high calcification (OR, 2.31; 95% CI, 0.89-5.99).
      CONCLUSIONS: In this sample of asymptomatic middle-aged women without known
      coronary disease, recurrent major depression was independently associated with
      coronary and aortic calcification. Waist-hip ratio in part mediated the
      association. Our findings suggest that recurrent major depression may be a risk
      factor for early atherosclerosis in women.

PMID- 15956002
TI  - Depressive symptoms and heart rate variability in postmenopausal women.
AB  - BACKGROUND: Depressive symptoms have been associated with increased cardiac
      morbidity and mortality rates, but the pathophysiologic mechanism linking
      depressive symptoms to cardiovascular outcome has yet to be fully understood.
      Lower heart rate variability has also been associated with increased risk of
      cardiac events in healthy individuals and in patients with coronary artery
      disease. Findings regarding a relationship between depressive symptoms and heart
      rate variability that could explain increased cardiovascular risk have been
      inconsistent across studies. METHODS: As an ancillary study to the Women's Health
      Initiative Observational Study, 3372 postmenopausal women aged 50 to 83 years
      were enrolled for further evaluation using 24-hour ambulatory
      electrocardiographic monitoring. A shortened version of the Center for
      Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule
      were administered. Women with adequate electrocardiographic data and depressive
      symptom information and without coronary artery disease were analyzed (n = 2627).
      RESULTS: Two hundred sixty-nine women (10.2%) had depressive symptoms as measured
      using the 2 instruments. Women with depressive symptoms had a higher mean +/- SD
      heart rate (77.4 +/- 9.6 vs 75.5 +/- 8.5 beats/min) and lower heart rate
      variability than women without depressive symptoms. All differences remained
      significant after adjusting for age (P<.01). CONCLUSIONS: Women with depressive
      symptoms had significant reductions in heart rate variability and higher heart
      rates, suggestive of increased sympathetic tone. These findings may contribute to
      the increased cardiac morbidity and mortality rates associated with depression in
      other studies.

PMID- 15956003
TI  - Calcium and vitamin D intake and risk of incident premenstrual syndrome.
AB  - BACKGROUND: Premenstrual syndrome (PMS) is one of the most common disorders of
      premenopausal women. Studies suggest that blood calcium and vitamin D levels are
      lower in women with PMS and that calcium supplementation may reduce symptom
      severity, but it is unknown whether these nutrients may prevent the initial
      development of PMS. METHODS: We conducted a case-control study nested within the
      prospective Nurses' Health Study II cohort. Participants were a subset of women
      aged 27 to 44 years and free from PMS at baseline in 1991, including 1057 women
      who developed PMS over 10 years of follow-up and 1968 women reporting no
      diagnosis of PMS and no or minimal menstrual symptoms. Intake of calcium and
      vitamin D was measured in 1991, 1995, and 1999 by a food frequency questionnaire.
      RESULTS: After adjustment for age, parity, smoking status, and other risk
      factors, women in the highest quintile of total vitamin D intake (median, 706
      IU/d) had a relative risk of 0.59 (95% confidence interval, 0.40-0.86) compared
      with those in the lowest quintile (median, 112 IU/d) (P = .01 for trend). The
      intake of calcium from food sources was also inversely related to PMS; compared
      with women with a low intake (median, 529 mg/d), participants with the highest
      intake (median, 1283 mg/d) had a relative risk of 0.70 (95% confidence interval,
      0.50-0.97) (P = .02 for trend). The intake of skim or low-fat milk was also
      associated with a lower risk (P<.001). CONCLUSIONS: A high intake of calcium and
      vitamin D may reduce the risk of PMS. Large-scale clinical trials addressing this
      issue are warranted. Given that calcium and vitamin D may also reduce the risk of
      osteoporosis and some cancers, clinicians may consider recommending these
      nutrients even for younger women.

PMID- 15956004
TI  - Prognostic value of combined exercise and recovery electrocardiographic analysis.
AB  - BACKGROUND: Heart rate-adjusted ST-segment depression (ST/HR) analysis improves
      the diagnostic accuracy of exercise testing, but its prognostic value has not
      been evaluated in unselected populations. We prospectively used comparative
      exercise-recovery ST/HR analysis to predict outcome in a consecutive cohort of
      outpatients referred for exercise testing. METHODS: The stress-recovery index,
      defined as the difference between ST/HR areas during exercise and recovery,was
      derived in 1163 patients (median age, 60 years; interquartile range, 54-65
      years). All-cause mortality and the combination of death or nonfatal myocardial
      infarction were target end points. The individual effect of clinical and exercise
      testing data on outcome was evaluated by Cox regression analysis using separate
      models for each group of variables. Model validation was performed using
      bootstrap methods adjusted by the degree of optimism in estimates. Survival
      analysis was performed with the product-limit Kaplan-Meier method. RESULTS:
      During a 33-month follow-up, 48 deaths and 72 nonfatal myocardial infarctions
      occurred. After adjusting for confounding variables, hypertension (hazard ratio,
      1.80; 95% confidence interval, 1.26-2.59), ST/HR index (hazard ratio, 1.32; 95%
      confidence interval, 1.04-1.66; for interquartile difference), and stress
      recovery index (hazard ratio, 0.75; 95% confidence interval, 0.65-0.86; for
      interquartile difference) were predictive of death or nonfatal myocardial
      infarction, whereas hypertension (hazard ratio, 3.67; 95% confidence interval,
      2.00-6.73) and stress-recovery index (hazard ratio, 0.55; 95% confidence
      interval, 0.48-0.63; for interquartile difference) were predictive of all-cause
      mortality. In addition, stress-recovery index increased the prognostic power of
      the model on top of clinical and exercise-testing variables and provided
      significant discrimination for survival. CONCLUSION: Combined evaluation of ST/HR
      analysis during exercise and recovery improves the prognostic capacity of
      standard exercise electrocardiography.

PMID- 15956005
TI  - Long-term risk for depressive symptoms after a medical diagnosis.
AB  - BACKGROUND: This study examines the risk of development of significant depressive
      symptoms after a new diagnosis of cancer, diabetes, hypertension, heart disease,
      arthritis, chronic lung disease, or stroke. METHODS: The study used 5 biennial
      waves (1992-2000) of the Health and Retirement Study to follow a sample of 8387
      adults (aged 51 to 61 years and without significant depressive symptoms in 1992)
      from 1994 to 2000. Time-dependent Cox regression models estimated adjusted hazard
      ratios (HRs) for an episode of significant depressive symptoms after a new
      diagnosis for each of the 7 medical conditions. RESULTS: Within 2 years of
      initial diagnosis, subjects with cancer had the highest hazard of depressive
      symptoms (HR, 3.55; 95% confidence interval [CI], 2.79-4.52), followed by
      subjects with chronic lung disease (HR, 2.21; 95% CI, 1.64-2.79) and heart
      disease (HR, 1.45; 95% CI, 1.09-1.93). The hazard for depressive symptoms for
      most of these diseases decreased over time; however, subjects with heart disease
      continued to have a higher risk for depressive symptoms even 2 to 4 years and 4
      to 8 years after diagnosis, and a significantly higher hazard for depressive
      symptoms developed for persons with arthritis 2 to 4 years after diagnosis (HR,
      1.46; 95% CI, 1.11-1.92). CONCLUSION: The findings identify several high-risk
      patient groups who might benefit from depression screening and monitoring to
      improve health outcomes in this vulnerable population facing new medical
      illnesses.

PMID- 15956006
TI  - Undertreatment of obese women receiving breast cancer chemotherapy.
AB  - BACKGROUND: Systematic undertreatment of breast cancer in overweight and obese
      women may contribute to the poorer prognosis in these women. The objective of
      this study was to investigate treatment patterns in overweight and obese women
      undergoing breast cancer adjuvant chemotherapy. METHODS: We performed a
      retrospective cohort study of 9672 women treated with doxorubicin hydrochloride
      and cyclophosphamide between 1990 and 2001. The main outcome measure was the
      quality of chemotherapy as measured by the use of reduced doses for the first
      treatment (compared with standard doses), the overall dose proportion (actual
      expected dose ratio), and relative dose intensity. RESULTS: First-cycle dose
      reductions (defined as a dose proportion of <0.9 compared with standard published
      doses) were administered to 9% of the healthy weight, 11% of the overweight, 20%
      of the obese, and 37% of the severely obese women (P<.001). First-cycle reduction
      was independently associated with being overweight (P = .03), obese (P<.001),
      severely obese (P<.001), older than 60 years (P<.001), and having a serious
      comorbid condition (P = .03). Practices varied greatly in the use of dose
      reductions in overweight and obese patients. Severe obesity was independently
      associated with a lower likelihood of admission for febrile neutropenia, even
      among those subjects given full weight-based doses (odds ratio, 0.61; 95%
      confidence interval, 0.38-0.97). CONCLUSIONS: Overweight and obese women with
      breast cancer often receive intentionally reduced doses of adjuvant chemotherapy.
      Administration of initial and overall full weight-based doses of adjuvant
      chemotherapy in overweight and obese women is likely to improve outcomes in this
      group of patients.

PMID- 15956007
TI  - Health-related quality of life as a predictor of hospital readmission and death
      among patients with heart failure.
AB  - BACKGROUND: We sought to examine the relationship between health-related quality
      of life (HRQL) and a first emergency rehospitalization and mortality in patients
      with heart failure (HF) having a wide variation in ventricular ejection fraction
      and functional status. METHODS: Prospective study conducted with 394 patients
      admitted for HF-related emergencies at 4 Spanish hospitals. Baseline HRQL was
      measured with a generic questionnaire, the Medical Outcomes Study 36-item Short
      Form Survey (SF-36), and with an HF-specific instrument, the Minnesota Living
      With Heart Failure (MLWHF) questionnaire. Cox proportional hazards models were
      used to calculate hazard ratios (HRs) for hospitalization and death on the basis
      of HRQL scores. RESULTS: During a median follow-up of approximately 6 months, 138
      patients (35.0%) underwent a first emergency rehospitalization and 70 (17.8%)
      died. After adjustment for biomedical, psychosocial, and health care variables,
      the frequency of hospital readmission was higher in patients with worse scores on
      the SF-36 physical functioning (HR, 1.65; 95% confidence interval [CI], 1.11
      2.44; P = .01), general health (HR, 1.73; 95% CI, 1.19-2.52; P = .003), and
      mental health (HR, 1.65; 95% CI, 1.10-2.47; P = .02) subscales. Results were
      similar for the mortality end point. For the MLWHF questionnaire, worse overall
      and worse physical and emotional summary scores were associated with higher
      mortality. CONCLUSIONS: Worse HRQL is associated with hospital readmission and
      death in patients with HF. The magnitude of this association, for both physical
      and mental HRQL components, is comparable to that for other well-known predictors
      of hospital readmission and death, such as personal history of diabetes, previous
      hospitalizations, and treatment with angiotensin-converting enzyme inhibitors.

PMID- 15956008
TI  - The quality of antipsychotic drug prescribing in nursing homes.
AB  - BACKGROUND: The prescribing of antipsychotic drugs has been increasing in nursing
      homes (NHs) since the availability of second-generation antipsychotic agents,
      also known as the atypicals, but there is little information on the
      appropriateness of such prescribing. METHODS: A retrospective analysis using the
      nationally representative data set of the Medicare Current Beneficiary Survey
      merged to Minimum Data Sets assessments, medication administration records, and
      Medicare claims. We identified a sample of 2.5 million Medicare beneficiaries in
      NHs during 2000-2001 (unweighted n = 1096) to assess prevalence of antipsychotic
      use, rates of adherence to NH prescribing guidelines, and changes in behavioral
      symptoms. RESULTS: Approximately 693 000 (unweighted n = 302), or 27.6%, of all
      Medicare beneficiaries in NHs received at least 1 prescription for antipsychotics
      during the study period: 20.3% received atypicals only; 3.7%, conventionals only;
      and 3.6%, both atypicals and conventionals. Less than half (41.8%) of treated
      residents received antipsychotic therapy in accordance with NH prescribing
      guidelines. One (23.4%) in 4 patients had no appropriate indication, 17.2% had
      daily doses exceeding recommended levels, and 17.6% had both inappropriate
      indications and high dosing. Patients receiving antipsychotic therapy within
      guidelines were no more likely to achieve stability or improvement in behavioral
      symptoms than were those taking antipsychotics outside the guidelines.
      CONCLUSIONS: This study detected the highest level of antipsychotic use in NHs in
      over a decade. Most atypicals were prescribed outside the prescribing guidelines
      and for doses and indications without strong clinical evidence. Failure to detect
      positive relationships between behavioral symptoms and antipsychotic therapy
      raises questions about the appropriateness of prescribing.

PMID- 15956009
TI  - Restless legs syndrome prevalence and impact: REST general population study.
AB  - BACKGROUND: Restless legs syndrome (RLS), a common sensorimotor disorder, has a
      wide range of severity from merely annoying to affecting sleep and quality of
      life severely enough to warrant medical treatment. Previous epidemiological
      studies, however, have failed to determine the prevalence of those with
      clinically significant RLS symptoms and to examine the life effects and medical
      experiences of this group. METHODS: A total of 16 202 adults (aged >/=18 years)
      were interviewed using validated diagnostic questions to determine the presence,
      frequency, and severity of RLS symptoms; respondents reporting RLS symptoms were
      asked about medical diagnoses and the impact of the disorder and completed the
      Short Form-36 Health Survey (SF-36). Criteria determined by RLS experts for
      medically significant RLS (frequency at least twice a week, distress at least
      moderate) defined "RLS sufferers" as a group most likely to warrant medical
      treatment. RESULTS: In all, 15 391 fully completed questionnaires were obtained;
      in the past year, RLS symptoms of any frequency were reported by 1114 (7.2%).
      Symptoms occurred at least weekly for 773 respondents (5.0%); they occurred at
      least 2 times per week and were reported as moderately or severely distressing by
      416 (2.7%). Of those 416 (termed RLS sufferers), 337 (81.0%) reported discussing
      their symptoms with a primary care physician, and only 21 (6.2%) were given a
      diagnosis of RLS. The SF-36 scores for RLS sufferers were significantly below
      population norms, matching those of patients with other chronic medical
      conditions. CONCLUSION: Clinically significant RLS is common (prevalence, 2.7%),
      is underdiagnosed, and significantly affects sleep and quality of life.

PMID- 15956010
TI  - Reduced loss of hand bone density with prednisolone in early rheumatoid
      arthritis: results from a randomized placebo-controlled trial.
AB  - BACKGROUND: Bone damage in rheumatoid arthritis presents as osteoporosis and
      joint erosions. Prednisolone has been shown to reduce the rate of hand joint
      destruction as seen on radiography but has not been shown to reduce the rate of
      hand bone loss. METHODS: In a double-blind study comparing oral prednisolone (7.5
      mg/d for 2 years) with placebo, hand bone density assessed with digital x-ray
      radiogrammetry was examined in 95 patients with rheumatoid arthritis with disease
      duration of less than 2 years. RESULTS: The mean loss of hand bone density was
      less in prednisolone-treated patients compared with placebo-treated patients at
      the 1-year follow-up (-0.011 vs -0.022 g/cm(2)) (P = .005) and at the 2-year
      follow-up (-0.026 vs -0.039 g/cm(2)) (P = .03). The mean percentage group
      difference in loss of hand bone density was 2.8% (P = .004) at the 1-year follow
      up and 3.5% (P = .01) at the 2-year follow-up. In the first year, C-reactive
      protein, a marker of inflammation, was strongly correlated with hand bone loss in
      placebo-treated patients but not in prednisolone-treated patients, suggesting
      that prednisolone breaks the link between bone loss and inflammation.
      CONCLUSIONS: To our knowledge, this is the first double-blind randomized study to
      show that disease-related loss of hand bone density in rheumatoid arthritis can
      be decelerated by prednisolone. This finding suggests that the deleterious effect
      of prednisolone on bone may be counteracted by its anti-inflammatory effect.

PMID- 15956011
TI  - Weight loss in overweight adults and the long-term risk of hypertension: the
      Framingham study.
AB  - BACKGROUND: Few studies address long-term effects of weight loss on risk of
      incident hypertension among overweight adults. METHODS: We evaluated weight loss
      among 623 overweight (body mass index [calculated as weight in kilograms divided
      by the square of height in meters] >/=25) middle-aged (aged 30-49 years) and 605
      overweight older (aged 50-65 years) adults in Framingham, Mass. Subjects were
      classified first according to amount of weight lost over 4 years: (1) weight
      changed by less than 1.8 kg (stable weight), (2) lost 1.8 to less than 3.6 kg,
      (3) lost 3.6 to less than 6.8 kg, and (4) lost 6.8 kg or more. We also classified
      weight loss according to whether it was sustained during the next 4 years.
      RESULTS: After adjusting for age, sex, education, baseline body mass index,
      height, activity, smoking, and alcohol intake, weight loss of 6.8 kg or more led
      to a 21% to 29% reduction in long-term hypertension risk. After adjusting for
      cancer or cardiovascular disease occurring during follow-up, weight loss of 6.8
      kg or more led to a 28% reduction in risk (relative risk [95% confidence
      interval], 0.72 [0.49-1.05]) for middle-aged adults and a 37% reduction (0.63
      [0.42-0.95]) for older adults. Sustained weight loss led to a 22% reduction in
      hypertension risk (0.78 [0.60-1.03]) among middle-aged and a 26% reduction (0.74
      [0.56-0.97]) in older adults. This risk reduction was strengthened by adjustment
      for prevalent cancer or cardiovascular disease during follow-up. CONCLUSION: A
      modest weight loss, particularly when sustained, substantially lowers the long
      term risk of hypertension in overweight adults.

PMID- 15956012
TI  - Circulating erythropoietin levels and prognosis in patients with congestive heart
      failure: comparison with neurohormonal and inflammatory markers.
AB  - BACKGROUND: Considerable morbidity and mortality are still associated with
      congestive heart failure (CHF) syndromes, despite improvement in therapy.
      Activation of neurohormonal, inflammatory, and oxidative mechanisms has been
      shown to contribute to the significant morbidity and mortality. Erythropoietin
      (EPO) is a cytokine known to regulate erythroid proliferation, attenuate
      apoptosis and oxidative stress, and promote angiogenesis. We prospectively
      evaluated the predictive value of baseline EPO, N-terminal pro-B-type natriuretic
      peptide, and C-reactive protein levels in patients with clinically controlled
      chronic CHF. METHODS: One hundred eighty-eight outpatients from a CHF clinic had
      baseline assessment of EPO, N-terminal pro-B-type natriuretic peptide, and C
      reactive protein levels and a complete clinical data profile. These patients were
      followed up for 24 months for any hospitalization due to CHF or mortality.
      RESULTS: Circulating EPO levels were higher in CHF patients and increased in
      subjects with higher New York Heart Association scores. Levels of EPO (at a
      cutoff of 23 mU/mL) and N-terminal pro-B-type natriuretic peptide (cutoff at the
      median of 1556 pg/mL) were found to be strong predictors of mortality and CHF
      hospitalization, whereas C-reactive protein levels (cutoff of 10 mg/L) predicted
      CHF hospitalizations but not mortality. Left ventricular ejection fraction was
      found to be a predictor of mortality but not of CHF hospitalizations. Serum
      levels of EPO were significantly correlated with N-terminal pro-B-type
      natriuretic peptide and C-reactive protein levels but not with left ventricular
      ejection fraction. CONCLUSION: If confirmed in large-scale clinical studies,
      determination of circulating EPO levels may aid in predicting morbidity and
      mortality in patients with clinically controlled congestive CHF.

PMID- 15956013
TI  - The (variable) definition of benefit in the case of clopidogrel vs aspirin.

PMID- 15956014
TI  - Heart failure management programs reduce readmissions and prolong survival.

PMID- 15956015
TI  - Can calcium channel blockers preserve renal function better than diuretics during
      antihypertensive treatment?

PMID- 15956016
TI  - Medical costs associated with chiropractic care.

PMID- 15956017
TI  - "Regression" of adiposity with more sleep.

PMID- 15956018
TI  - Quebec reports C. difficile mortality statistics.

PMID- 15956019
TI  - Osthole-mediated cell differentiation through bone morphogenetic protein-2/p38
      and extracellular signal-regulated kinase 1/2 pathway in human osteoblast cells.
AB  - The survival of osteoblast cells is one of the determinants of the development of
      osteoporosis in patients. Osthole (7-methoxy-8-isopentenoxycoumarin) is a
      coumarin derivative present in many medicinal plants. By means of alkaline
      phosphatase (ALP) activity, osteocalcin, osteopontin, and type I collagen, enzyme
      linked immunosorbent assay, we have shown that osthole exhibits a significant
      induction of differentiation in two human osteoblast-like cell lines, MG-63 and
      hFOB. Induction of differentiation by osthole was associated with increased bone
      morphogenetic protein (BMP)-2 production and the activations of SMAD1/5/8 and p38
      and extracellular signal-regulated kinase (ERK) 1/2 kinases. Addition of purified
      BMP-2 protein did not increase the up-regulation of ALP activity and osteocalcin
      by osthole, whereas the BMP-2 antagonist noggin blocked both osthole and BMP-2
      mediated ALP activity enhancement, indicating that BMP-2 production is required
      in osthole-mediated osteoblast maturation. Pretreatment of osteoblast cells with
      noggin abrogated p38 activation but only partially decreased ERK1/2 activation,
      suggesting that BMP-2 signaling is required in p38 activation and is partially
      involved in ERK1/2 activation in osthole-treated osteoblast cells. Cotreatment of
      p38 inhibitor SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)-1H-imidazole] or p38 small interfering RNA (siRNA) expression inhibited
      osthole-mediated activation of ALP but only slightly affected osteocalcin
      production. In contrast, the production of osteocalcin induced by osthole was
      inhibited by the mitogen-activated protein kinase kinase inhibitor PD98059 (2'
      amino-3'-methoxyflavone) or by expression of an ERK2 siRNA. These data suggest
      that BMP-2/p38 pathway links to the early phase, whereas ERK1/2 pathway is
      associated with the later phase in osthole-mediated differentiation of osteoblast
      cells. In this study, we demonstrate that osthole is a promising agent for
      treating osteoporosis.

PMID- 15956020
TI  - Protein-embedding technique: a potential approach to standardization of
      immunohistochemistry for formalin-fixed, paraffin-embedded tissue sections.
AB  - A serial study was performed to develop a protein-embedding technique for
      standardization of immunohistochemistry (IHC) on formalin-fixed, paraffin
      embedded (FFPE) tissue sections. A protein carrier matrix must have two phases, a
      liquid phase to allow uniform mixing of a protein and a solid phase forming a
      'block' that can be fixed and processed in the same manner as human tissue. This
      standardized protein block would serve as a source of thin sections for control
      of IHC and therefore must also withstand the boiling conditions of antigen
      retrieval (AR). After multiple experiments, a method was developed utilizing
      polymer microsphere (beads) as a support medium for protein. The method showed
      particular promise for quantitative IHC.

PMID- 15956021
TI  - Association between endocrine pancreas and ductal system. More than an
      epiphenomenon of endocrine differentiation and development?
AB  - Traditional histological descriptions of the pancreas distinguish between the
      exocrine and the endocrine pancreas, as if they were two functionally distinct
      glands. This view has been proven incorrect and can be considered obsolete.
      Interactions between acinar and islet tissues have been well established through
      numerous studies that reveal the existence of anatomical and functional
      relationships between these compartments of the gland. Less attention, however,
      has traditionally been paid to the relationships occurring between the endocrine
      pancreas and the ductal system. Associations between islet tissue and ducts are
      considered by most researchers as only a transient epiphenomenon of endocrine
      development. This article reviews the evidence that has emerged in the last 10
      years demonstrating the existence of stable, close, and systematic relationships
      between these two pancreatic compartments. Functional and pathophysiological
      implications are considered, and the existence of an "acinar-duct-islet" axis is
      put forward. The pancreas appears at present to be an integrated organ composed
      of three functionally related components of well-orchestrated endocrine and
      exocrine physiological responses.

PMID- 15956022
TI  - Standardization of the immunocytochemical detection of neuroblastoma cells in
      bone marrow.
AB  - Standard cytomorphological examination of bone marrow (BM) aspirates does not
      appear to be sensitive enough to detect single neuroblastoma cells. The SIOPEN
      Neuroblastoma Bone Marrow Committee developed a sensitive and reproducible anti
      GD2 immunocytochemical assay and introduced morphological and immunocytological
      criteria for the interpretation of results. Fixed cytospins were incubated with a
      commercially available anti-GD2 monoclonal antibody and an APAAP kit. Cells
      fulfilling all morphological and immunocytological criteria were called criteria
      positive cells (CPCs). Not convincingly interpretable cells fulfilled some, but
      not all, criteria, and negative cells displayed only exclusion criteria. The
      genetic profile of doubtful cells was checked by fluorescence in situ
      hybridization. Ideally, 3 x 10(6) cells were analyzed to reach a 95% probability
      of detecting one tumor cell in 1 x 10(6) mononuclear cells. Four quality control
      rounds were organized to validate the method. A total of 111 quality control
      samples were analyzed. Two main improvements were achieved: in discordant cases,
      the range between the lowest and highest reported result was reduced by half, and
      discordant results were only found in samples with less than 10 CPCs per 1 x
      10(6). This article describes the first internationally standardized protocol to
      detect and quantify rare neuroblastoma cells by immunocytochemistry. This method
      is an indispensable tool for multicenter studies evaluating the clinical
      significance of minimal residual disease in neuroblastoma.

PMID- 15956024
TI  - Differential cellular expression of galectin family mRNAs in the epithelial cells
      of the mouse digestive tract.
AB  - Galectin is an animal lectin that recognizes beta-galactosides of glycoconjugates
      and is abundant in the gut. This study revealed the cellular expression of
      galectin subtypes throughout the mouse digestive tract by in situ hybridization.
      Signals for five subtypes (galectin-2, -3, -4/6, and -7) were detected
      exclusively in the epithelia. In the glandular stomach, galectin-2 and -4/6 were
      predominantly expressed from gastric pits to neck of gastric glands, where mucous
      cells were the main cellular sources. The small intestine exhibited intense,
      maturation-associated expressions of galectin-2, -3, and -4/6 mRNAs. Galectin-2
      was intensely expressed from crypts to the base of villi, whereas transcripts of
      galectin-3 gathered at villous tips. Signals for galectin-4/6 were most intense
      at the lower half of villi. Galectin-2 was also expressed in goblet cells of the
      small intestine but not in those of the large intestine. In the large intestine,
      galectin-4/6 predominated, and the upper half of crypts simultaneously contained
      transcripts of galectin-3. Stratified epithelium from the lip to forestomach and
      anus intensely expressed galectin-7 with weak expressions of galectin-3. Because
      galectins in the digestive tract may be multi-functional, information on their
      cell/stage-specific expression contributes to a better understanding of the
      functions and pathological involvements of galectins.

PMID- 15956023
TI  - Histochemical analyses of altered fetal lung development following single vs
      multiple courses of antenatal steroids.
AB  - A single course of antenatal steroids is widely used during preterm labor to
      promote fetal lung maturation. However, little is known regarding efficacy and
      safety of multiple courses of antenatal steroids. In animal models and clinical
      trials, treatment with glucocorticoids can inhibit growth. The present study of
      single- vs multiple-course steroids in pregnant ewes analyzes the effects of
      steroids vs placebo on fetal lung histopathology. Single-course groups received
      dexamethasone (Dex) 6 mg or normal saline every 12 hr for 48 hr at 104-106 days
      of gestation (term = 150 days). Multiple-course groups received the first course
      at 76-78 days; this was repeated weekly for 5 weeks. At 108 days, lungs were
      analyzed using immunohistochemistry for alpha-smooth muscle actin, a
      myofibroblast marker and proliferating cell nuclear antigen. Cell injury/death
      was evaluated using TdT-mediated dUTP digoxigenin nick end labeling (TUNEL)
      analysis. Although fetal growth was restricted by either single or multiple
      courses of Dex, alveolar development was accelerated as measured by mean linear
      intercepts. Alveolar walls were thinner, developing septa were longer, and septal
      myofibroblasts were increased for both Dex groups compared with controls. Cell
      proliferation increased following multiple steroid courses, especially in the
      distal parenchyma, with a corresponding decrease in apoptosis. These observations
      suggest that Dex promotes alveolarization, whether given in single or multiple
      courses.

PMID- 15956025
TI  - Nuclear expression of thymidylate synthase in colorectal cancer cell lines and
      clinical samples.
AB  - Thymidylate synthase (TS) [TYMS; OMIM reference number (188,350)] is normally
      considered to be a cytoplasmic enzyme. However, a few reports have suggested it
      may also be present in the nucleus. To explore this in more detail, we used a
      highly specific polyclonal antibody to TS and a combination of techniques,
      including immunocytochemistry, confocal microscopy, cell fractionation, and
      Western blotting. We developed cell line HeLa-55, a HeLa derivative that grossly
      overexpresses TS. Although the vast majority of TS was in the cytoplasm, some TS
      also was seen in the nucleus. TS in parental HeLa cells and in normal human
      fibroblasts was seen exclusively in the cytoplasm. HeLa-55 cells exposed to 5
      fluorodeoxyuridine were fractionated and examined by Western blotting.
      Interestingly, both free TS and the ternary complex of TS were seen in the
      cytoplasmic fraction but only free TS was detected in the nuclear fraction.
      Amongst different cell lines examined, HCT-15 and normal fibroblasts showed no
      nuclear TS, HCC-2998 and SW-620 showed a small amount of nuclear TS, and HT-29,
      RKO, and HCT-116 showed a strong nuclear TS signal. Nuclear staining was clearly
      evident in some clinical colorectal specimens, both normal and malignant. This
      staining was definitively shown to be TS by competition with recombinant TS
      protein. A putative leucine-rich nuclear export sequence was identified but its
      function could not be confirmed. We conclude that small amounts of TS protein is
      present in the nucleus of some cell types but further work is needed to determine
      the significance of this observation.

PMID- 15956026
TI  - Immunoexpression of Tyro 3 family receptors--Tyro 3, Axl, and Mer--and their
      ligand Gas6 in postnatal developing mouse testis.
AB  - Tyro 3 family receptors contain three members-Tyro 3, Axl, and Mer-that are
      essential regulators of mammalian spermatogenesis. However, their exact
      expression patterns in testis are unclear. In this study, we examined the
      localizations of Tyro 3, Axl, Mer, and their ligand Gas6 in postnatal mouse
      testes by immunohistochemistry. All three members and their ligand were
      continuously expressed in different testicular cells during postnatal
      development. Tyro 3 was expressed only in Sertoli cells with a varied
      distribution during testis development. At day 3 postnatal, Tyro 3 was
      distributed in overall cytoplasmic membrane and cytoplasm of Sertoli cells. From
      day 14 to day 35 postnatal, Tyro 3 appeared on Sertoli cell processes toward the
      adlumenal compartment of seminiferous tubules. A stage-dependent Tyro 3
      immunoexpression in Sertoli cells was shown by adulthood testis at day 56
      postnatal with higher expression at stages I-VII and lower level at stages IX
      XII. Axl showed a similar expression pattern to Tyro 3, except for some
      immunopositive Leydig cells detected in mature testis. In contrast,
      immunostaining of Mer was detected mainly in primitive spermatogonia and Leydig
      cells, whereas a relative weak signal was found in Sertoli cells. Gas6 was
      strongly expressed in Leydig cells, and a relative weak staining signal was seen
      in primitive spermatogonia and Sertoli cells. These immunoexpression patterns of
      Tyro 3 family receptors and ligand in testis provide a basis to further study
      their functions and mechanisms in regulating mammalian spermatogenesis.

PMID- 15956027
TI  - Development of in situ zymography to localize active matrix metalloproteinase-7
      (matrilysin-1).
AB  - Matrix metalloproteinase-7 (MMP-7) is upregulated during carcinogenesis and its
      expression correlates with metastasis of human endometrial and gastrointestinal
      carcinomas. In the present study, we have developed a new method to localize the
      activity of MMP-7 within tissues. Polyethylene terephthalate films were uniformly
      coated with crosslinked carboxymethylated transferrin (CCm-Tf) as a substrate and
      incubated with frozen tissue sections mounted on the films. CCm-Tf on the films
      was degraded selectively by MMP-7, but showed little or no susceptibility to MMP
      1, -2, -3, -9, or -13; MT1-MMP; MT3-MMP; or ADAMTS4. Although some serine
      proteinases such as elastase also digested CCm-Tf, CCm-Tf films impregnated with
      serine proteinase inhibitors prevented the digestion. When frozen sections of
      human endometrial carcinoma and lung carcinoma tissues were incubated on CCm-Tf
      films or those treated with proteinase inhibitors, the activity was detected in
      the carcinoma cell nests, where MMP-7 was immunolocalized. The present in situ
      zymography using CCm-Tf may be a useful method to analyze the functions of MMP-7
      in pathophysiological conditions.

PMID- 15956028
TI  - Provinol prevents CsA-induced nephrotoxicity by reducing reactive oxygen species,
      iNOS, and NF-kB expression.
AB  - Cyclosporine A (CsA) use is associated with several side effects, the most
      important of which is nephrotoxicity that includes, as we previously showed,
      tubular injury and interstitial fibrosis. Recently, many researchers have been
      interested in minimizing these effects by pharmacological interventions. To do
      this, we tested whether the administration of a red wine polyphenol, Provinol
      (PV), prevents the development of CsA-induced nephrotoxicity. Rats were treated
      for 21 days and divided into four groups: control; group treated with PV (40
      mg/kg/day by oral administration in tap water); group treated with CsA (15
      mg/kg/day by subcutaneous injection); group treated with CsA plus PV. CsA
      produced a significant increase of systolic blood pressure; it did not affect
      urinary output, but caused a significant decrease in creatinine clearance. These
      side effects were associated with an increase in conjugated dienes, which are
      lipid peroxidation products, inducible NO-synthase (iNOS), and nuclear factor
      (NF)-kB, which are involved in antioxidant damage. However, PV prevented these
      negative effects through a protective mechanism that involved reduction of both
      oxidative stress and increased iNOS and NF-kB expression induced by CsA. These
      results provide a pharmacological basis for the beneficial effects of plant
      derived polyphenols against CsA-induced renal damage associated with CsA.

PMID- 15956029
TI  - Chemiluminescence quantitative immunohistochemical determination of MRP2 in liver
      biopsies.
AB  - Evaluation of protein expression in tissues and cells by electrophoretic and
      blotting techniques or by the quantification of the mRNA coding for the target
      protein is a common procedure in biochemistry research and clinical diagnoses. In
      this article, an alternative approach, based on an immunohistochemical procedure
      with chemiluminescent imaging detection, is described. The assay exploited the
      peculiar characteristics of the chemiluminescent detection of enzyme labels (high
      sensitivity and specificity, low background, easy quantification of the signal)
      for performing the direct, simple, and rapid quantitative evaluation of protein
      expression in tissues. When applied to the study of the levels of MRP2, a member
      of the human multidrug resistance-associated protein family, in samples obtained
      from formalin-fixed, paraffin-embedded liver biopsies, it allowed the reliable
      evaluation of the protein content of the tissue. Moreover, the analysis of
      clinical samples from patients with primary biliary cirrhosis under therapy with
      ursodeoxycholic acid gave results in line with those, previously reported in the
      literature, obtained with conventional protein expression analysis techniques.

PMID- 15956030
TI  - Discrimination of cell nuclei in early S-phase, mid-to-late S-phase, and G(2)/M
      phase by sequential administration of 5-bromo-2'-deoxyuridine and 5-chloro-2'
      deoxyuridine.
AB  - 5-Bromo-2'-deoxyuridine (BrdU) and 5-chloro-2'-deoxyuridine (CldU) were
      sequentially administered intraperitoneally into mice at 1-hr intervals. After
      one additional hr, the small intestines were resected, fixed, and embedded in
      paraffin. In histological sections stained with monoclonal antibody Br-3 reactive
      to both BrdU and CldU, and CldU antibody reactive only to CldU, three types of
      staining could be identified in the proliferating zone. Cells with nuclei stained
      only with Br-3 antibody were estimated to have completed DNA replication during
      the first 1 hr and were fixed in G(2)/M-phase. Those nuclei were frequently found
      in apical areas of the simple columnar epithelium of the intestine, whereas other
      nuclei were located basally in the cells. This observation suggested
      intracellular movement of cell nuclei in G(2)/M-phase. Identification of cells in
      early S-phase became possible using these antibodies in combination with DAB and
      fluorescence stainings. Replication sites in early S-phase nuclei were found to
      be numerous, whereas in late S-phase they were larger in size and much smaller in
      number.

PMID- 15956031
TI  - Localization of alpha-dystroglycan on the podocyte: from top to toe.
AB  - alpha-Dystroglycan (DG) is a negatively charged membrane-associated glycoprotein
      that links the cytoskeleton to the extracellular matrix. Previously, we described
      that alpha-DG covers the whole podocyte cell membrane in the rat. However, our
      finding was challenged by the description of a strictly basolateral localization
      in human kidney biopsies, using a different antibody against alpha-DG. Therefore,
      we studied the exact localization of glomerular alpha-DG by using these two
      antibodies in both species. The studies were performed by using monoclonal
      antibodies (MoAbs) IIH6 and VIA4.1 in immunofluorescence, confocal microscopy,
      and immunoelectron microscopy on both rat and human kidney sections, as well as
      on cultured mouse podocytes. The apical localization of alpha-DG on podocytes was
      more dominant than the basolateral localization. The basolateral staining with
      MoAb VIA4.1 was more pronounced than that of MoAb IIH6. With both MoAbs, the
      staining in rat kidneys was more prominent, in comparison to human kidneys. We
      conclude that alpha-DG is expressed at both the basolateral and apical sides of
      the podocyte. This localization suggests that alpha-DG plays a dual role in the
      maintenance of the unique architecture of podocytes by its binding to the
      glomerular basement membrane, and in the maintenance of the integrity of the
      filtration slit, respectively.

PMID- 15956032
TI  - Expression of a wild-type CFTR maintains the integrity of the
      biosynthetic/secretory pathway in human cystic fibrosis pancreatic duct cells.
AB  - The structural integrity of the Golgi complex is essential to its functions in
      the maturation, sorting, and transport of plasma membrane proteins. Previously,
      we demonstrated that in pancreatic duct CFPAC-1 cells, which express DeltaF508
      CFTR (cystic fibrosis transmembrane conductance regulator), the intracellular
      trafficking of carbonic anhydrase IV (CA IV), a membrane protein involved in
      HCO(3)(-) secretion, was impaired. To determine whether these abnormalities were
      related to changes in the Golgi complex, we examined the ultrastructure and
      distribution of Golgi compartments with regard to the microtubule cytoskeleton in
      CFPAC-1 cells transfected or not with the wild-type CFTR. Ultrastructural and
      immunocytochemical analysis showed that in polarized CFPAC-1 cells, Golgi stacks
      were disconnected from one another and scattered throughout the cytoplasm. The
      colocalization of CA IV with markers of Golgi compartments indicated the ability
      of stacks to transfer this enzyme. This Golgi dispersal was associated with
      abnormal microtubule distribution and multiplicity of the microtubule-organizing
      centers (MTOCs). In reverted cells, the normalization of Golgi structure,
      microtubule distribution, and MTOC number was observed. These observations
      suggest that the entire biosynthetic/secretory pathway is disrupted in CFPAC-1
      cells, which might explain the abnormal intracellular transport of CA IV. Taken
      together, these results point to the fact that the expression of DeltaF508 CFTR
      affects the integrity of the secretory pathway.

PMID- 15956033
TI  - Connective tissue growth factor and cardiac fibrosis after myocardial infarction.
AB  - The temporal and spatial expression of transforming growth factor (TGF)-beta(1)
      and connective tissue growth factor (CTGF) was assessed in the left ventricle of
      a myocardial infarction (MI) model of injury with and without angiotensin
      converting enzyme (ACE) inhibition. Coronary artery ligated rats were killed 1,
      3, 7, 28, and 180 days after MI. TGF-beta(1), CTGF, and procollagen alpha1(I)
      mRNA were localized by in situ hybridization, and TGF-beta(1) and CTGF protein
      levels by immunohistochemistry. Collagen protein was measured using picrosirius
      red staining. In a separate group, rats were treated for 6 months with an ACE
      inhibitor. There were temporal and regional differences in the expression of TGF
      beta(1), CTGF, and collagen after MI. Procollagen alpha1(I) mRNA expression
      increased in the border zone and scar peaking 1 week after MI, whereas collagen
      protein increased in all areas of the heart over the 180 days. Expression of TGF
      beta(1) mRNA and protein showed major increases in the border zone and scar
      peaking 1 week after MI. The major increases in CTGF mRNA and protein occurred in
      the viable myocardium at 180 days after MI. Long-term ACE inhibition reduced left
      ventricular mass and decreased fibrosis in the viable myocardium, but had no
      effect on cardiac TGF-beta(1) or CTGF. TGF-beta(1) is involved in the initial,
      acute phase of inflammation and repair after MI, whereas CTGF is involved in the
      ongoing fibrosis of the heart. The antifibrotic benefits of captopril are not
      mediated through a reduction in CTGF.

PMID- 15956034
TI  - The subcellular localization of syntaxin 17 varies among different cell types and
      is altered in some malignant cells.
AB  - Syntaxin 17 (STX17) is a divergent member of the syntaxin family of proteins
      first discovered by Scheller and colleagues in a yeast two-hybrid screen designed
      to identify novel mammalian SNAREs (soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors). We recently independently identified STX17 as a
      novel Ras-interacting protein, but immunohistochemical studies suggested that
      STX17 is localized to the nucleus in normal pancreatic ductal epithelial, acinar,
      and islet cells in contrast to previous reports of cytoplasmic localization,
      albeit in other cell types. Therefore, we have conducted a more thorough survey
      of various human and mouse tissues to better establish the expression pattern of
      STX17 in different tissues and cell types. Although RT-PCR experiments
      demonstrate ubiquitous expression of STX17, closer examination by
      immunohistochemistry reveal that STX17 expression is limited to certain cell
      types. Furthermore, in contrast to the cytoplasmic localization previously
      reported in a limited number of cell types, we find that in many other cell
      types, syntaxin 17 can be found in the nucleus. Finally, we demonstrate that in
      human hepatocellular carcinoma cell lines, STX17 localization is altered relative
      to normal hepatocytes, although the localization of STX17 differs even between
      these established human cancer cell lines and fresh human hepatocellular
      carcinoma cells, emphasizing the caution that must be exercised in drawing
      conclusions from data gathered in cell lines. The sequence divergence of STX17,
      the unexpected nuclear localization of STX17 in many cell types, and the altered
      localization of STX17 in malignant cells argue for a novel function of syntaxin
      17 distinct from its hypothesized role in mediating membrane fusion events.

PMID- 15956035
TI  - The EGFR mutation and its correlation with response of gefitinib in previously
      treated Chinese patients with advanced non-small-cell lung cancer.
AB  - BACKGROUND: The aim of the study was to evaluate the efficacy of gefitinib and
      the epidermal growth factor receptor (EGFR) mutation to gefitinib response in a
      series of Chinese patients with pretreated advanced non-small-cell lung cancer
      (NSCLC). METHODS: A total of 98 patients who had failed at least one platinum
      based regimen received gefitinib 250 mg once daily. The mutation analysis of the
      EGFR kinase domain was performed for 30 patients using paraffin-embedded tumor
      tissue. RESULTS: The response rate was 31.6% and the disease control rate was
      67.3%. Objective response was correlated with adenocarcinoma, female gender and
      non-smokers. Median progress free survival (PFS) was 7.0 months, median overall
      survival (OS) was 12.0 months and 1-year survival was 53.1%. The median PFS and
      OS were improved among patients with adenocarcinoma, gefitinib responders and non
      smokers. Active gene mutation was detected in 12 patients. Mutation rates were
      higher among gefitinib responders, non-smokers, patients with adenocarcinoma and
      female patients. OS was longer for patients with gene mutation than for patients
      without mutation. CONCLUSION: Gefitinib demonstrated significant antitumor
      activity with a favorable toxicity profile for pretreated Chinese patients with
      advanced NSCLC. The active mutation of the EGFR kinase domain was strongly
      associated with response to gefitinib and prolonged overall survival.

PMID- 15956036
TI  - Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric
      cancer.
AB  - BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer.
      This phase II study was designed to evaluate the activity and safety of an
      epirubicin, cisplatin and docetaxel combination in patients with this disease.
      PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with
      measurable distant metastasis were eligible for the study. Patients received
      epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60
      mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day
      subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for
      a maximum of eight courses. RESULTS: All patients were evaluable for response and
      toxicity. Two complete and 21 partial responses were observed, with an overall
      response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease
      was observed in 13 patients (28%) and progressive disease in 10 patients (22%).
      The median time to progression was 6 months (95% CI 5-7) and the median overall
      survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia,
      thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients,
      respectively. There were five episodes of febrile neutropenia in four patients.
      Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in
      four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac
      toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The
      epirubicin, cisplatin and docetaxel combination is an active and well tolerated
      novel chemotherapy regimen for treating metastatic gastric cancer and deserves
      further evaluation in randomized studies.

PMID- 15956037
TI  - Breast cancer recurrence dynamics following adjuvant CMF is consistent with tumor
      dormancy and mastectomy-driven acceleration of the metastatic process.
AB  - PURPOSE: The aim of this study was to better understand human breast cancer
      biology by studying how the timing of metastasis following primary resection is
      affected by adjuvant CMF (cyclophoshamide, methotrexate, 5-fluorouracil)
      chemotherapy. PATIENTS AND METHODS: Discrete hazards of recurrence and recurrence
      risk reductions for treated patients relative to controls were analyzed for all
      patients enrolled in two separate randomized clinical trials [study 1 (386
      women): no further treatment versus 12 cycles of CMF; study 2 (459 women): six
      versus 12 cycles of CMF] and a historical group (396 women: surgery alone) of
      axillary node-positive patients undergoing mastectomy. RESULTS: (i) Nearly all
      CMF benefit occurs during the first 4 years following resection/chemotherapy.
      (ii) The CMF recurrence rate reduction is largely restricted to two specific
      spans. These temporally separate recurrence clusters occur during the first and
      third year of follow-up, while the second-year recurrences are weakly affected.
      (iii) Prolonging adjuvant treatment from 6 to 12 months partially alters this
      recurrence timing, without appreciably affecting the overall recurrence rate.
      (iv) These effects upon the dynamics of post-resection occurrence are menopausal
      status-independent. CONCLUSIONS: At least two different therapeutically
      vulnerable proliferative events, resulting in clinical appearance of two
      metastasis temporally distinct clusters of post-resection cancer recurrence,
      apparently occur during the administration of adjuvant chemotherapy. Metastases
      that transpire outside of these temporal windows are refractory to adjuvant
      therapy. The dynamics of both post-treatment recurrence risk and CMF
      effectiveness are similar for both pre- and postmenopausal women, suggesting that
      post-resection mechanisms by which chemotherapy prevents metastases are similar,
      but of different magnitude in pre- and postmenopausal women. These findings are
      consistent with a metastasis model that includes tumor dormancy in specific
      micrometastatic phases (single cells and avascular foci) and with the
      acceleration of the metastatic process by the surgical resection of the primary
      breast cancer.

PMID- 15956038
TI  - Primary chemotherapy in operable breast carcinoma comparing CMF
      (cyclophosphamide, methotrexate, 5-fluorouracil) with an anthracycline-containing
      regimen: short-term responses translated into long-term outcomes.
AB  - BACKGROUND: The role of anthracyclines has been extensively studied in adjuvant
      chemotherapy, but much less in the primary chemotherapy of early breast
      carcinoma. This study, comparing CMF (cyclophosphamide, methotrexate, 5
      fluorouracil) with the rotational anthracycline-containing regimen CMFEV (CMF
      plus epirubicin and vincristine) administered as primary chemotherapy,
      demonstrated a significant increase in clinical complete response in
      premenopausal women. We report the long-term results. PATIENTS AND METHODS: Two
      hundred and eleven patients with stage I or II palpable breast carcinoma and a
      tumour diameter of >2.5 cm were randomised to receive CMF or CMFEV for four
      cycles before surgery. After surgery, the patients in both arms received adjuvant
      CMF for three cycles. RESULTS: In the study population as a whole, there was a
      non-significant 20% reduction in mortality and relapse rates in the CMFEV arm.
      However, the effect of the experimental regimen was only found in premenopausal
      patients, especially in terms of relapse-free survival (P=0.07) and locoregional
      relapse-free survival (P=0.0009), thus mirroring the effect on response rates.
      After 10 years, the proportions of premenopausal patients free from locoregional
      relapse as a first event in the CMF and CMFEV groups were 68% and 97%,
      respectively. No relevant differences were found in postmenopausal patients.
      CONCLUSION: The overall results of this study showed that the greater activity of
      the experimental anthracycline-containing combination over CMF as primary
      chemotherapy in premenopausal patients translated into long-term effects in the
      same subgroup.

PMID- 15956039
TI  - Pretreatment prognostic factors and treatment outcome in elderly patients with de
      novo acute myeloid leukemia.
AB  - BACKGROUND: Elderly patients with acute myeloid leukemia (AML) generally have an
      unfavorable clinical course and are under-represented in clinical trials. The aim
      of this study was to analyze the prognosis and treatment outcome of elderly AML
      patients. PATIENTS AND METHODS: We studied 205 AML patients aged 65 years or
      older at our hospital. Prior to study initiation, we designated 13 variables to
      be analyzed for their impact on complete remission (CR) rate and overall survival
      (OS). RESULTS: Induction regimen (standard chemotherapy) and good performance
      status (PS) (Eastern Cooperative Oncology Group PS 0-1) independently influenced
      the achievement of CR. Multivariate analysis also determined five poor prognostic
      factors for OS: poor PS (score 2-4), presence of comorbidities, elevated serum
      lactate dehydrogenase level (> or =2x upper normal limit), extreme leukocytosis
      (> or =100 x 10(9)/l) and marked thrombocytopenia (< or =20 x 10(9)/l). Age was
      not an independent contributing factor in terms of either CR attainment or OS
      duration. Low-risk patients, who possessed one or less non-leukocytosis poor
      prognostic factor, had significantly longer disease-free survival and OS than
      their high-risk counterparts. CONCLUSIONS: Elderly AML patients should be risk
      stratified at diagnosis. Anthracycline-based induction chemotherapy would be the
      best therapeutic option for such patients.

PMID- 15956040
TI  - Wavelength dependent responses of primary human keratinocytes to combined
      treatment with benzo[a]pyrene and UV light.
AB  - The major risk factor for skin cancer is exposure to UV radiation from sunlight,
      but other environmental exposures may also play a role in combination with UV. We
      have studied the effects of combined exposure of primary human skin cells in
      vitro to UVA, UVB or UVC with benzo[a] pyrene (BaP), an environmental carcinogen.
      Normal human keratinocytes were exposed to 5 microM BaP for 24 h followed by
      either 1 kJ/m(2) UVA, 100 J/m(2) UVB or 10 J/m(2) UVC. Only BaP + UVA caused
      increased cell death. BaP or UVA alone did not induce significant DNA damage as
      measured by comet assay but combined exposure induced 35.1 +/- 6.0% tail DNA,
      compared with 9.7 +/- 1.3% tail DNA in control cells. After including the Fapy
      DNA glycosylase enzyme incubation step to detect oxidized purines, % tail DNA
      increased another 11.2 +/- 2.9%. Combined exposure of BaP and UVB did not
      increase damage in the comet assay without Fapy-DNA glycosylase, but in the
      presence of this enzyme % tail DNA increased by 9.3 +/- 2.2%. BaP + UVB also
      abrogated the UVB-induced cell cycle G2 arrest. BaP + UVC had no effect on the
      keratinocytes compared with each treatment alone. These results show a wavelength
      dependent difference in the effects of combined exposure on normal human
      keratinocytes. Both UVA and UVB damage can be enhanced by BaP pre-exposure,
      although the effects seen with UVA were greater. These findings are important to
      understanding the role of UVA and UVB in skin carcinogenesis and may have
      implications for recommended sun exposure limits, especially in polluted areas.

PMID- 15956041
TI  - Radioprotective potential of ginseng.
AB  - A majority of potential radioprotective synthetic compounds have demonstrated
      limited clinical application owing to their inherent toxicity, and thus, the
      seeking of naturally occurring herbal products, such as ginseng, for their
      radioprotective capability has become an attractive alternative. In general,
      ginseng refers to the roots of the species of the genus Panax. As a medicinal
      herb, ginseng has been widely used in traditional Chinese medicine for its wide
      spectrum of medicinal effects, such as tonic, immunomodulatory, antimutagenic,
      adaptogenic and antiaging activities. Many of its medicinal effects are
      attributed to the triterpene glycosides known as ginsenosides (saponins). This
      review addresses the issue of the radioprotective effects of ginseng on mammalian
      cells both in vitro and in vivo. Results indicate that the water-soluble extract
      of whole ginseng appears to give a better protection against radiation-induced
      DNA damage than does the isolated ginsenoside fractions. Since free radicals play
      an important role in radiation-induced damage, the underlying radioprotective
      mechanism of ginseng could be linked, either directly or indirectly, to its
      antioxidative capability by the scavenging free radicals responsible for DNA
      damage. In addition, ginseng's radioprotective potential may also be related to
      its immunomodulating capabilities. Ginseng is a natural product with worldwide
      distribution, and in addition to its antitumor properties, ginseng appears to be
      a promising radioprotector for therapeutic or preventive protocols capable of
      attenuating the deleterious effects of radiation on human normal tissue,
      especially for cancer patients undergoing radiotherapy.

PMID- 15956042
TI  - The Genome Health Clinic and Genome Health Nutrigenomics concepts: diagnosis and
      nutritional treatment of genome and epigenome damage on an individual basis.
AB  - The evidence of a direct link between increased genome/epigenome damage and
      elevated risk for adverse health outcomes during the various stages of life, such
      as infertility, foetal development and cancer is becoming increasingly stronger.
      The latter is briefly reviewed against a background of evidence indicating that
      genome and epigenome damage biomarkers, in the absence of overt exposure of
      genotoxins, are themselves sensitive indicators of deficiency in micronutrients
      required as cofactors or as components of DNA repair enzymes, for maintenance
      methylation of CpG sequences and prevention of DNA oxidation and/or uracil
      incorporation into DNA. The latter is illustrated with cross-sectional and
      dietary intervention data obtained using the micronucleus assay and other
      efficient biomarkers for diagnosing genome and/or epigenome instability. The
      concept of recommended dietary allowances for genome stability and how this could
      be achieved is discussed. The 'Genome Health Nutrigenomics' concept is also
      introduced to define and focus attention on the specialized research area of how
      diet impacts on genome stability and how genotype determines nutritional
      requirements for genome health maintenance. The review concludes with a vision
      for a paradigm shift in disease prevention strategy based on the diagnosis and
      nutritional treatment of genome/epigenome damage on an individual basis, i.e. The
      Genome Health Clinic.

PMID- 15956043
TI  - Genotoxic damage in zebra fish (Danio rerio) by arsenic in waters from Zimapan,
      Hidalgo, Mexico.
AB  - The induction of micronuclei in gill cells of zebra fish (Danio rerio) maintained
      in calcium-magnesium bicarbonated waters from a reference well and 'Zimapan 5'
      well, the latter with an arsenic (As) content ranging from 0.395 to 0.630 p.p.m.,
      was studied. The specimens were studied during 180 days in three separated lots:
      in reference well-water (negative control), in reference water to which was added
      5 mg/l As(5+) (positive control); and in water from 'Zimapan 5' well, with 65
      specimens/lot. In waters an As concentration diminution was observed with time,
      whereas in fish there was an increase. After 30 days there was an As diminution
      in water from positive control of 1092.65 p.p.b. (36.42 p.p.b./day), whereas in
      fish it had increased to 523.81 p.p.b. (17.46 p.p.b./day). For the water from
      'Zimapan 5' well, there was a diminution of 211.40 p.p.b. (7.04 p.p.b./day), and
      in fish there was an increase of 74.73 p.p.b. (2.49 p.p.b./day). In relation to
      micronucleus frequency in gill cells, at the end of 180 days in the negative
      control there was a spontaneous generation of 0.8 micronuclei/1000 cells, in the
      positive control there was a micronucleus frequency 163.5 times greater than in
      the negative control, whereas for the fish exposed to 'Zimapan 5' well-water the
      micronucleus frequency was 56.25 times greater than in the negative control.
      Taken together these results demonstrate the genotoxicity to Danio rerio of As in
      the well water.

PMID- 15956044
TI  - Influence of orange juice over the genotoxicity induced by alkylating agents: an
      in vivo analysis.
AB  - There is considerable epidemiological evidence indicating an association between
      diets rich in fresh fruit and vegetables and a decreased incidence of cancers.
      Methyl methanesulfonate (MMS) and cyclophosphamide (CP) are alkylating agents
      that differ in their mode of action. MMS is a directly-acting, monofunctional
      agent, while CP is a bifunctional agent that requires metabolic activation to a
      reactive metabolite. To evaluate if orange juice could reduce DNA damage induced
      by these alkylating agents, mice were treated orally (by gavage) with MMS and CP,
      prior to and after treatment with orange juice. DNA damage was evaluated by the
      comet assay in peripheral white blood cells. Under these experimental conditions,
      orange juice reduced the extent of DNA damage caused by both mutagens. For MMS,
      the antigenotoxic effect of the orange juice was both protective (orange juice
      pre-treatment) and reparative (orange juice post-treatment); for CP, the effect
      was reparative only. The components of orange juice can have several biological
      effects, including acting as targets of toxicants and modulating
      metabolization/detoxification routes. Considering the different mechanisms of the
      action of the two drugs, different protective effects are suggested. These
      results demonstated the ability of the in vivo comet assay to detect in vivo
      modulation of MMS and CP mutagenicity by orange juice.

PMID- 15956045
TI  - The re-emerging burden of rickets: a decade of experience from Sydney.
AB  - AIM: To define the demographics and clinical characteristics of cases presenting
      with nutritional rickets to paediatric centres in Sydney, Australia. METHODS:
      Retrospective descriptive study of 126 cases seen from 1993 to 2003 with a
      diagnosis of vitamin D deficiency and/or confirmed rickets defined by long bone x
      ray changes. RESULTS: A steady increase was seen in the number of cases per year,
      with a doubling of cases from 2002 to 2003. Median age of presentation was 15.1
      months, with 25% presenting at less than 6 months of age. The most common
      presenting features were hypocalcaemic seizures (33%) and bowed legs (22%). Males
      presented at a younger age, with a lower weight SDS, and more often with
      seizures. The caseload was almost exclusively from recently immigrated children
      or first generation offspring of immigrant parents, with the region of origin
      predominantly the Indian subcontinent (37%), Africa (33%), and the Middle East
      (11%). Seventy nine per cent of the cases were born in Australia. Eleven cases
      (all aged <7 months) presented atypically with hyperphosphataemia. CONCLUSIONS:
      This large case series shows that a significant and increasing caseload of
      vitamin D deficiency remains, even in a developed country with high sunlight
      hours. Cases mirror recent immigration trends. Since birth or residence in
      Australia does not appear to be protective, screening of at risk immigrant
      families should be implemented through public health policies.

PMID- 15956046
TI  - Overweight and obesity trends from 1974 to 2003 in English children: what is the
      role of socioeconomic factors?
AB  - AIMS: To examine the childhood overweight and obesity prevalence trends between
      1974 and 2003 and to assess whether these trends relate to parental social class
      and household income. METHODS: A school based and a general population health
      survey: the National Study of Health and Growth in 1974, 1984, and 1994, and the
      Health Survey for England, yearly from 1996 to 2003. Participants were 14,587
      white boys and 14,014 white girls aged 5-10 years. Overweight and obesity
      prevalence were calculated using UK specific as well as international body mass
      index (kg/m2) cut-offs. Socioeconomic status was measured using the Registrar
      General's social class; household income (1997 onwards only) was adjusted for
      household size. RESULTS: The prevalence of obesity (UK specific definition) in
      boys increased from 1.2% in 1984 to 3.4% in 1996-97 and 6.0% in 2002-03. In
      girls, obesity increased from 1.8% in 1984 to 4.5% in 1996-97 and 6.6% in 2002
      03. Obesity prevalence has been increasing at accelerating rates in the more
      recent years. Children from manual social classes had marginally higher odds (OR
      1.14, 95% CI 0.98 to 1.33) and children from higher income households had lower
      odds (OR 0.74, 95% CI 0.61 to 0.89) to be obese than their peers from non-manual
      class, and lower income households, respectively. CONCLUSION: Childhood obesity
      is increasing rapidly into the 2000s in England and these increases are more
      marked among children from lower socioeconomic strata. There is an urgent need
      for action to prevent further increase in obesity among children.

PMID- 15956047
TI  - Milk versus medicine for the treatment of iron deficiency anaemia in hospitalised
      infants.
AB  - AIMS: To compare iron fortified follow-on milk (iron follow-on), iron fortified
      partially modified cows' milk (iron milk), and iron medicine for the treatment of
      iron deficiency anaemia (IDA) in hospitalised infants. METHODS: In a randomised
      controlled trial, infants aged 9-23 months with IDA and who were hospitalised
      with an acute illness received iron follow-on (12 mg/l ferrous iron), iron milk
      (12.9 mg/l ferrous iron), or iron medicine (ferrous gluconate at 3 mg/kg of
      elemental iron once daily). All interventions were given for three months.
      Changes in measures of iron status three months after hospital discharge were
      determined. RESULTS: A total of 234 infants were randomised. Iron status was
      measured at follow up in 59 (70%) iron medicine, 49 (66%) iron follow-on, and 54
      (70%) iron milk treated infants. There was a significant (mean, 95% CI) increase
      in haemoglobin (15 g/l, 13 to 16) and iron saturation (9%, 8 to 10) and decrease
      in ferritin (-53 microg/l, -74 to -31) in all three groups. Mean cell volume
      increased in iron follow-on (2 fl, 1 to 3) and iron milk (1 fl, 0.1 to 3) treated
      infants, but not in the iron medicine group (1 fl, -1 to 2). The proportion with
      IDA decreased in all three groups: iron medicine 93% to 7%, iron follow-on 83% to
      8%, and iron milk 96% to 30%. Adverse effects, primarily gastrointestinal,
      occurred in 23% of the iron medicine, 14% of the iron follow-on, and 13% of the
      iron milk group. CONCLUSIONS: Iron fortified follow-on milk, iron fortified
      partially modified cows' milk, and iron medicine all effectively treat IDA in
      infancy.

PMID- 15956048
TI  - Growth in children with Helicobacter pylori infection and dyspepsia.
AB  - AIMS: To compare the height, weight, and body mass index (BMI) of children
      presenting with dyspeptic symptoms and Helicobacter pylori infection, to those
      with dyspepsia but without the infection. METHODS: A retrospective chart review
      of 257 children was performed. 13C urea breath test was performed to detect H
      pylori infection; weight and height were recorded and BMI was calculated. Weight,
      height, and BMI SD scores were determined using the 1990 UK normative data. The
      Index of Multiple Deprivation 2004 (IMD 2004) scores, which measure deprivation
      at small area level, were calculated from the patients' postcodes. RESULTS:
      Ninety seven of the 257 children were H pylori positive. The mean age at
      diagnosis and presenting symptoms of H pylori positive and negative patients were
      similar. The mean IMD 2004 scores for children with H pylori infection were
      significantly higher compared to H pylori negative patients, suggesting that
      children with the infection came from relatively more deprived areas. The mean
      weight and height SD score were significantly lower for children with H pylori
      infection compared to those without. However, this difference was no longer
      significant after adjusting for socioeconomic deprivation and ethnic differences
      between the groups. CONCLUSION: Children with dyspepsia and H pylori infection
      were shorter and lighter than patients with similar symptoms but no infection.
      The differences in anthropometry may be due to socioeconomic and ethnic factors
      rather than H pylori infection.

PMID- 15956049
TI  - AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of
      starved/carbohydrate-refed rats.
AB  - Acute increases in the concentration of malonyl-CoA play a pivotal role in
      mediating the decrease in fatty acid oxidation that occurs in many tissues during
      refeeding after a fast. In this study, we assess whether such increases in
      malonyl-CoA in liver could be mediated by malonyl-CoA decarboxylase (MCD), as
      well as acetyl-CoA carboxylase (ACC). In addition, we examine how changes in the
      activity of ACC, MCD, and other enzymes that govern fatty acid and glycerolipid
      synthesis relate temporally to alterations in the activities of the fuel-sensing
      enzyme AMP-activated protein kinase (AMPK). Rats starved for 48 h and refed a
      carbohydrate chow diet for 1, 3, 12, and 24 h were studied. Refeeding caused a
      40% decrease in the activity of the alpha1-isoform of AMPK within 1 h, with
      additional decreases in AMPKalpha1 activity and a decrease in AMPKalpha2
      occurring between 1 and 24 h. At 1 h, the decrease in AMPK activity was
      associated with an eightfold increase in the activity of the alpha1-isoform of
      ACC and a 30% decrease in the activity of MCD, two enzymes thought to be
      regulated by AMPK. Also, the concentration of malonyl-CoA was increased by 50%.
      Between 1 and 3 h of refeeding, additional increases in the activity of ACC and
      decreases in MCD were observed, as was a further twofold increase in malonyl-CoA.
      Increases in the activity (60%) and abundance (12-fold) of fatty acid synthase
      occurred predominantly between 3 and 24 h and increases in the activity of
      mitochondrial sn-glycerol-3-phosphate acyltransferase (GPAT) and acyl
      CoA:diaclyglycerol acyltransferase (DGAT) at 12 and 24 h. The results strongly
      suggest that early changes in the activity of MCD, as well as ACC, contribute to
      the increase in hepatic malonyl-CoA in the starved-refed rat. They also suggest
      that the changes in these enzymes, and later occurring increases in enzymes
      regulating fatty acid and glycerolipid synthesis, could be coordinated by AMPK.

PMID- 15956050
TI  - Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs.
AB  - Hemorrhagic coagulopathy is involved in the morbidity and mortality of trauma
      patients. Nonetheless, many aspects of the mechanisms underlying this disorder
      are poorly understood. We have therefore investigated changes in fibrinogen
      metabolism and coagulation function after a moderate hemorrhagic shock, using a
      new stable isotope approach. Twelve pigs were randomly divided into the control
      (C) and hemorrhage (H) groups. Hemorrhage was induced by bleeding 35% total blood
      volume over a 30-min period. A primed constant infusion of [1-(13)C]phenylalanine
      (Phe), d5-phenylalanine, and alpha-[1-(13)C]-ketoisocaproate (KIC) was given to
      quantify fibrinogen synthesis and breakdown, together with measurements of
      circulating liver enzyme activities and coagulation function. Mean arterial
      pressure was decreased by hemorrhage from 89 +/- 4 mmHg in C to 47 +/- 4 mmHg in
      H (P < 0.05), followed by a rebound to 68 +/- 5 mmHg afterward. Fibrinogen
      fractional synthesis rate increased from 2.7 +/- 0.2%/h in C to 4.2 +/- 0.4%/h in
      H by Phe (P < 0.05) and from 3.1 +/- 0.4%/h in C to 4.4 +/- 0.5%/h in H by KIC (P
      < 0.05). Fibrinogen fractional breakdown rate increased from 3.6 +/- 1.0%/h in C
      to 12.9 +/- 1.8%/h in H (P < 0.05). The absolute breakdown rate accelerated from
      3.0 +/- 0.4 mg x kg(-1) x h(-1) in C to 5.4 +/- 0.6 mg x kg(-1) x h(-1) in H (P <
      0.05), but the absolute synthesis rate remained unchanged. These metabolic
      changes were accompanied by a reduction in blood clotting time to 92.7 +/- 1.6%
      of the baseline value by hemorrhage (P < 0.05). No changes were found in liver
      enzyme activities. We conclude that the observed changes in coagulation after
      hemorrhagic shock are mechanistically related to the acute acceleration of
      fibrinogen degradation.

PMID- 15956051
TI  - Comparative analysis of ACTH and corticosterone sampling methods in rats.
AB  - A frequently debated question for studies involving the measurement of stress
      hormones in rodents is the optimal method for collecting blood with minimal
      stress to the animal. Some investigators prefer the implantation of indwelling
      catheters to allow for frequent sampling. Others argue that the implantation of a
      catheter creates a chronic stress to the animal that confounds stress hormone
      measures and therefore rely on tail vein sampling. Moreover, some investigators
      measure hormones in trunk blood samples obtained after anesthesia, a practice
      that may itself raise hormone levels. To address these controversies, we 1)
      compared plasma ACTH and corticosterone (Cort) concentrations in pre- and
      poststress rat blood samples obtained via previously implanted vena cava
      catheters, tail vein nicks, or clipping the tip off the tail and 2) compared
      plasma ACTH and Cort in rat blood samples obtained by decapitation with and
      without anesthesia. Rats sampled via indwelling catheters displayed lower
      prestress ACTH levels than those sampled by tail vein nick if the time to acquire
      samples was not limited; however, elevated basal ACTH was not observed in samples
      obtained by tail clip or tail nick when the samples were obtained within 3 min.
      Baseline Cort levels were similar in all groups. After restraint stress, the
      profile of the plasma ACTH and Cort responses was not affected by sampling
      method. Decapitation with prior administration of CO2 or pentobarbital sodium
      increased plasma ACTH levels approximately 13- and 2-fold, respectively, when
      compared with decapitation without anesthesia. These data indicate that tail vein
      nicking, tail clipping, or indwelling venous catheters can be used for obtaining
      plasma for ACTH and Cort during acute stress studies without confounding the
      measurements. However, the elevation in basal ACTH seen in the tail vein nick
      group at baseline suggests that sampling needs to be completed rapidly (<3 min)
      to avoid the initiation of the pituitary stress response. Death by CO2 and
      pentobarbital sodium injection before trunk blood collection cause significant
      stress to animals, as reflected in the elevated plasma ACTH levels. These results
      support the use of either chronic vascular cannulas or sampling from a tail vein.
      However, collection of blood under pentobarbital sodium or CO2 anesthesia is
      likely to confound the results of stress studies when ACTH is an important
      endpoint.

PMID- 15956052
TI  - Role of high-voltage-activated calcium channels in glucose-regulated beta-cell
      calcium homeostasis and insulin release.
AB  - High-voltage-activated (HVA) calcium channels are known to be the primary source
      of calcium for glucose-stimulated insulin secretion. However, few studies have
      investigated how these channels can be regulated by chronically elevated levels
      of glucose. In the present study, we determined the level of expression of the
      four major HVA calcium channels (N-type, P/Q-type, L(C)-type, and L(D)-type) in
      rat pancreatic beta-cells. Using quantitative real-time PCR (QRT-PCR), we found
      the expression of all four HVA genes in rat insulinoma cells (INS-1) and in
      primary isolated rat islet cells. We then determined the role of each channel in
      insulin secretion by using channel-selective antagonists. Insulin secretion
      analysis revealed that N- and L-type channels are both involved in immediate
      glucose-induced insulin secretion. However, L-type was preferentially coupled to
      secretion at later time points. P/Q-type channels were not found to play a role
      in insulin secretion at any stage. It was also found that long-term exposure to
      elevated glucose increases basal calcium in these cells. Interestingly,
      chronically elevated glucose decreased the mRNA expression of the channels
      involved with insulin secretion and diminished the level of stimulated calcium
      influx in these cells. Using whole cell patch clamp, we found that N- and L-type
      channel currents increase gradually subsequent to lower intracellular calcium
      perfusion, suggesting that these channels may be regulated by glucose-induced
      changes in calcium.

PMID- 15956053
TI  - Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting
      neurons, causing elevated plasma oxytocin level in rats.
AB  - We examined the effects of intracerebroventricular (i.c.v.) administration of
      adrenomedullin 2 (AM2) on plasma oxytocin (OXT) and arginine vasopressin (AVP)
      levels in conscious rats. Plasma OXT levels were markedly increased 5 min after
      i.c.v. administration of AM2 (1 nmol/rat) compared with vehicle and remained
      elevated in samples taken at 10, 15, 30, and 60 min. By contrast, plasma AVP
      levels were not significantly elevated in samples taken between 5 and 180 min
      after i.c.v. administration of AM2 except at the 30-min time point. Fos-like
      immunoreactivity (Fos-LI) was observed in various brain areas, including the
      paraventricular (PVN) and the supraoptic nuclei (SON) after i.c.v. administration
      of AM2 (2 nmol/rat) in conscious rats (measured at 90 min post-AM2 infusion).
      Dual immunostaining for OXT/Fos and AVP/Fos showed that OXT-LI neurons
      predominantly exhibited nuclear Fos-LI compared with AVP-LI neurons in the PVN
      and the SON. In situ hybridization histochemistry showed that i.c.v.
      administration of AM2 (0.2, 1, and 2 nmol/rat) caused marked induction of the
      expression of the c-fos gene in the PVN and the SON. This induction was
      significantly reduced by pretreatment with both the calcitonin gene-related
      peptide (CGRP) antagonist CGRP-(8-37) (3 nmol/rat) and the AM receptor antagonist
      AM-(22-52) (27 nmol/rat). These results suggest that centrally administered AM2
      mainly activates OXT-secreting neurons in the PVN and the SON, at least in part
      through the CGRP and/or AM receptors with marked elevation of plasma OXT levels
      in conscious rats.

PMID- 15956054
TI  - IL-6 is not required for parathyroid hormone stimulation of RANKL expression,
      osteoclast formation, and bone loss in mice.
AB  - Continuous elevation of parathyroid hormone (PTH) increases osteoclast
      precursors, the number of osteoclasts on cancellous bone, and bone turnover. The
      essential molecular mediators of these effects are controversial, however, and
      both increased receptor activator of NF-kappaB ligand (RANKL) and IL-6 have been
      implicated. The goal of these studies was to determine whether continuous
      elevation of endogenous PTH alters IL-6 gene expression in vivo and whether IL-6
      is required for PTH-induced bone loss. To accomplish this, we generated
      transgenic mice harboring a luciferase reporter gene under the control of IL-6
      gene regulatory regions to allow accurate quantification of IL-6 gene activity in
      vivo. In these mice, induction of secondary hyperparathyroidism using a calcium
      deficient diet did not alter IL-6-luciferase transgene expression, whereas RANKL
      mRNA expression was elevated in bone tissue. Moreover, secondary
      hyperparathyroidism induced an equivalent amount of bone loss in wild-type and IL
      6-deficient mice, and PTH elevated RANKL mRNA and osteoclast formation to the
      same extent in bone marrow cultures derived from wild-type and IL-6-deficient
      mice. These results demonstrate that IL-6 is not required for the osteoclast
      formation and bone loss that accompanies continuous elevation of PTH.

PMID- 15956055
TI  - Insured but not protected: how many adults are underinsured?
AB  - Health insurance is in the midst of a design shift toward greater financial risk
      for patients. Where medical cost exposure is high relative to income, the shift
      will increase the numbers of underinsured people. This study estimates that
      nearly sixteen million people ages 19-64 were underinsured in 2003. Underinsured
      adults were more likely to forgo needed care than those with more adequate
      coverage and had rates of financial stress similar to those of the uninsured.
      Including adults uninsured during the year, 35 percent (sixty-one million) were
      under- or uninsured. These findings highlight the need for policy attention to
      insurance design that considers the adequacy of coverage.

PMID- 15956056
TI  - Revisiting mortality predictability of serum albumin in the dialysis population:
      time dependency, longitudinal changes and population-attributable fraction.
AB  - BACKGROUND: Hypoalbuminaemia is a marker of malnutrition-inflammation complex
      syndrome (MICS) and a strong predictor of cardiovascular (CV) death in
      maintenance haemodialysis (MHD) patients. However, serum albumin may change over
      time. Hence, its time-varying associations with outcome may be different.
      METHODS: Associations between 3-month averaged serum albumin levels, measured in
      a single laboratory using bromocresol green, and CV mortality were studied
      longitudinally in a 2-year cohort of 58,058 MHD patients. Mortality
      predictability of fixed baseline and trimonthly-varying serum albumin
      concentrations were compared. RESULTS: Hazard ratios (HRs) of CV death strictly
      increased across decrements of baseline serum albumin, whereas the HR for time
      varying serum albumin decrements below 3.8 g/dl did not differ. A drop in serum
      albumin in the first 6 months was associated with increasing all-cause and CV
      death risks in the subsequent 18 months, while a rise in serum albumin was a
      predictor of better survival independent of baseline serum albumin. The
      multivariate adjusted population-attributable fraction of death due to baseline
      serum albumin <3.8 g/dl was 19%. CONCLUSIONS: Time-varying hypoalbuminaemia
      predicts all-cause and CV death differently from fixed measures of serum albumin
      in MHD patients. An increase in serum albumin over time is associated with better
      survival independent of baseline serum albumin or other MICS surrogates. If this
      association is causal, an intervention that could increase serum albumin >3.8
      g/dl might reduce the number of MHD deaths in the USA by approximately 10,000
      annually. Nutritional interventions examining benefits of increasing serum
      albumin in MHD patients are urgently needed.

PMID- 15956057
TI  - A dramatic reduction of normalized protein catabolic rate occurs late in the
      course of progressive renal insufficiency.
AB  - BACKGROUND: Spontaneous reduction in dietary protein intake is a recognized
      feature of severe renal failure, and previous studies have suggested that this
      may occur at an early stage of renal functional decline. METHODS: We examined the
      effects of progressive renal insufficiency on the normalized protein catabolic
      rate (nPCR) in 1282 patients (mean age 55.8+/-15.5 years; 60.4% male) over a 7
      year period. All values of nPCR (n = 5082) obtained before commencement of
      dialysis were included. A total of 361 (28.2%) patients later developed end-stage
      renal failure and were started on dialysis. RESULTS: Cross-sectional analysis
      showed nPCR being significantly less at lower creatinine clearance. Mean nPCR was
      1.17+/-0.31 at a clearance >50, 1.04+/-0.27 at 25-50, 0.93+/-0.21 at 10-25 and
      0.74+/-0.18 at <10 ml/min. Mean nPCR in each clearance group was different from
      that in all other groups (P<0.001 in all cases). When nPCR was studied
      longitudinally in relation to time of initiation of dialysis, the fall in nPCR
      only became significant in the 3 months preceding initiation. Curve fitting
      suggested a two-phase exponential association between nPCR and renal function, a
      gentle decline of nPCR in mild and moderate renal failure culminating in a
      dramatic decline when CrCl reached 15 ml/min and weekly Kt/V(urea) 2.5. nPCR at
      dialysis initiation predicted survival on dialysis even when corrected for age,
      diabetes and non-renal co-morbid load. However, it was no longer significant when
      residual renal function was included in the model. The group initiating dialysis
      with a normal nPCR maintained this throughout the first 3 years on dialysis
      whilst the group initiating with a low nPCR, though improving initially,
      continued to have significantly lower nPCR levels throughout follow-up than their
      normal nPCR counterparts. CONCLUSION: A significant reduction of nPCR occurs late
      in progressive renal insufficiency and may predict the need for dialysis
      initiation. nPCR levels <0.8 at initiation predict future low nPCR levels and
      mortality on dialysis. The correlation between nPCR and CrCl in early renal
      insufficiency may be partly artefactual.

PMID- 15956058
TI  - Renal accumulation of pentosidine in non-diabetic proteinuria-induced renal
      damage in rats.
AB  - BACKGROUND: Advanced glycation end-products (AGEs) contribute to the pathogenesis
      of diabetic glomerulopathy. The role of AGEs in non-diabetic renal damage is not
      well characterized. First, we studied whether renal AGE accumulation occurs in
      non-diabetic proteinuria-induced renal damage and whether this is ameliorated by
      renoprotective treatment. Secondly, we investigated whether renal AGE
      accumulation was due to intrarenal effects of local protein trafficking. METHODS:
      Pentosidine was measured (by high-performance liquid chromatography) in rats with
      chronic bilateral adriamycin nephropathy (AN), untreated and treated with
      lisinopril. Age-matched healthy rats served as negative controls. Secondly, we
      compared renal pentosidine in mild proteinuric and non-proteinuric kidneys of
      unilateral AN and in age-matched controls at 12 and 30 weeks. Intrarenal
      localization of pentosidine was studied by immunohistochemistry. RESULTS: Renal
      pentosidine was elevated in untreated AN (0.14+/-0.04 micromol/mol valine) vs
      healthy controls (0.04+/-0.01 micromol/mol valine, P<0.01). In lisinopril-treated
      AN, pentosidine was lower (0.09+/-0.02 micromol/mol valine) than in untreated AN
      (P<0.05). In unilateral proteinuria, pentosidine was similar in non-proteinuric
      and proteinuric kidneys. After 30 weeks of unilateral proteinuria, pentosidine
      was increased in both kidneys (0.26+/-0.10 micromol/mol valine) compared with
      controls (0.18+/-0.06 micromol/mol valine, P<0.05). Pentosidine (AN, week 30) was
      also increased compared with AN at week 12 (0.16+/-0.06 micromol/mol valine,
      P<0.01). In control and diseased kidneys, pentosidine was present in the
      collecting ducts. In proteinuric kidneys, in addition, pentosidine was present in
      the brush border and cytoplasm of dilated tubular structures, i.e. at sites of
      proteinuria-induced tubular damage. CONCLUSION: Pentosidine accumulates in non
      diabetic proteinuric kidneys in damaged tubules, and renoprotective treatment by
      angiotensin-converting enzyme (ACE) inhibitors inhibits AGE accumulation,
      supporting a relationship between abnormal renal protein trafficking, proteinuria
      induced tubular damage and tubular pentosidine accumulation. Future studies,
      applying specific AGE inhibitors, should be conducted to provide insight into the
      pathophysiological significance of renal AGEs in non-diabetic renal disease.

PMID- 15956059
TI  - Membranous glomerulonephritis with monoclonal immune deposits and crescents.

PMID- 15956060
TI  - The safety of sodium ferric gluconate complex in haemodialysis patients has been
      extensively evaluated.

PMID- 15956061
TI  - Intrarenal arterial aneurysms with haematuria in a patient with tuberous
      sclerosis complex.

PMID- 15956062
TI  - L-carnitine and erythropoiesis: relationship with haeme oxygenase-1.

PMID- 15956063
TI  - MIBI scintigraphy, indicators of cell proliferation and histology of parathyroid
      glands in uraemic patients.
AB  - BACKGROUND: Although scintigraphy with (99m)Tc-sestamibi (MIBI) has been used to
      localize parathyroid glands prior to surgery for hyperparathyroidism, using it to
      evaluate parathyroid function remains controversial. The purpose of this study
      was to evaluate the possible association of MIBI uptake with gland weight,
      histological pattern and proliferative activity of parathyroid cells. METHODS: We
      studied 18 patients with secondary hyperparathyroidism (SHP); mean age 38+/-3
      years, 55% female, mean time on haemodialysis 7.7+/-0.9 years. All patients had
      parathyroidectomy (PTx). The weights of the removed glands were estimated, and
      parathyroid hyperplasia was classified as diffuse (n = 28) or nodular (n = 29).
      The expression of proliferative cell nuclear antigen (PCNA) was evaluated by
      immunohistochemistry. Before PTx, all patients underwent MIBI evaluation and were
      categorized using a 0-3 uptake scoring system. Low uptake (scores of 0 and 1) was
      seen in 39 glands and high uptake (scores of 2 and 3) in 18. RESULTS: Estimated
      gland weights, percentage of nodular hyperplasia and PCNA expression were greater
      in glands with high MIBI scores than in those with low scores (P<0.01). In glands
      with nodular hyperplasia, PCNA expression was higher (318+/-66 cells/mm2) than in
      those with diffuse hyperplasia (104+/-16 cells/mm2; P<0.001). CONCLUSIONS: High
      MIBI scores were associated with high estimated gland weight, degree of cell
      proliferation and presence of nodular hyperplasia. MIBI scintigraphy is useful in
      clinical practice for localizing parathyroid glands, and it could guide the
      management of SHP by indicating the degree of its severity.

PMID- 15956065
TI  - Is the term 'renal support therapy' more appropriate than 'renal replacement
      therapy'?

PMID- 15956064
TI  - Altered status of glutathione and its metabolites in cystinotic cells.
AB  - BACKGROUND: Cystinosis is an autosomal recessive disorder, caused by mutations of
      the lysosomal cystine carrier cystinosin, encoded by the CTNS gene (17p13). The
      concomitant intralysosomal cystine accumulation leads to multi-organ damage, with
      kidneys being the first affected. Altered mitochondrial oxidative phosphorylation
      has been demonstrated in animal proximal tubules loaded with cystine dimethyl
      ester, mimicking cystine accumulation in cystinosis, but has not been confirmed
      in cells of patients with cystinosis. Furthermore, the link between cystine
      accumulation and mitochondrial damage is also missing. We hypothesized that
      cytosolic cysteine deficiency resulting in intracellular glutathione (GSH)
      shortage might be involved in cellular dysfunction in cystinosis. METHODS:
      Components of the gamma-glutamyl cycle were measured in cultured skin fibroblasts
      (n = 9) and polymorphonuclear (PMN) leukocytes (n = 15) derived from patients
      with cystinosis and compared with the values in cultured fibroblasts (n = 9) and
      PMN cells (n = 18) of healthy controls. RESULTS: Cystine content in cystinotic
      fibroblasts and PMN cells was significantly elevated compared with the controls,
      consistent with the lysosomal cystine accumulation in these cells. Although no
      reduction of total intracellular GSH content was found in cystinotic cells, it
      inversely correlated with cystine levels. Furthermore, GSH disulfide (GSSG) was
      elevated in cystinotic cells, resulting in an increased GSSG/total GSH (%) ratio.
      No relationship between intracellular cystine and GSH was found in control
      fibroblasts and PMN cells. CONCLUSION: An elevated GSSG/total GSH (%) ratio might
      indicate increased oxidative stress present in cystinotic cells. Inverse
      correlation between cystine accumulation and intracellular GSH content indicates
      that under stress conditions such as intensive energy demand or increased
      oxidative insult, cystinotic cells may be more prone to GSH depletion.

PMID- 15956066
TI  - Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal
      syndrome: a retrospective study.
AB  - BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis and
      is associated with high mortality. Ornipressin and terlipressin are effective in
      treatment of HRS, but are not available in the USA. The efficacy of vasopressin
      (AVP) and octreotide (OCT) infusions, commonly utilized in the USA, in the
      treatment of HRS is unknown. This study aims to evaluate the effects of AVP and
      OCT on renal function, systemic haemodynamics and clinical outcomes in HRS.
      METHODS: This observational study evaluated patients receiving AVP or OCT therapy
      for HRS from January 2000 to December 2003. Recovery from HRS was defined as a
      decrease in the serum creatinine (SCr) to a value < or =1.5 mg/dl. RESULTS: Forty
      three patients were identified: eight received AVP, 16 received OCT and 19
      received both AVP and OCT. Patients who received AVP alone or in combination with
      OCT had significantly greater recovery rates than those receiving OCT monotherapy
      (42 vs 38 vs 0%, respectively, P = 0.01). The average time to response in serum
      creatinine (SCr) was 7+/- 2 days. The mean AVP doses were 0.23+/-0.19 U/min in
      patients demonstrating clinical response. Therapy with AVP was an independent
      predictor of recovery (odds ratio 6.4, 95% confidence interval 1.3-31.8).
      Patients who responded to therapy had significantly lower mortality (23 vs 67%, P
      = 0.008) and higher rates of liver transplantation (23 vs 0%, P = 0.005). No
      adverse effects related to AVP therapy were observed. CONCLUSION: When compared
      with OCT, HRS patients treated with AVP had significantly higher recovery rates,
      improved survival and were more likely to receive a liver transplant.

PMID- 15956067
TI  - Chronic organizing microangiopathy in a renal transplant recipient.

PMID- 15956068
TI  - Primary hyperoxaluria: from gene defects to designer drugs?

PMID- 15956069
TI  - Renal protection in IgA nephropathy requires strict blood pressure control.

PMID- 15956070
TI  - Sodium retention in rats with liver cirrhosis is associated with increased renal
      abundance of NaCl cotransporter (NCC).
AB  - BACKGROUND: Liver cirrhosis is associated with enhanced renal tubular sodium
      retention, the mechanism of which is still debated. We hypothesized that liver
      cirrhosis is associated with increased expression of renal epithelial sodium
      transporter(s). METHODS: Liver cirrhosis was induced by bile duct ligation (BDL)
      in rats. Steady state mRNA of ENaC subunits alpha, beta, gamma serum and
      glucocorticoid inducible kinase (Sgk1) were measured by TaqMan PCR in kidney
      homogenates at week 1, 2, 3 and 4 after BDL. Renal protein content of ENaC
      subunits, ubiquitin-protein-ligase Nedd4-2 and NaCl cotransporter (NCC) were
      assessed by western blot. Subcellular localization of ENaC subunits and NCC were
      analysed by immunohistochemistry. RESULTS: Steady state mRNA of ENaC alpha, beta
      and gamma were unchanged during the 4 weeks investigated, while ENaC protein
      decreased most prominently at week 2 (control vs BDL; alpha, -46%; beta, -81%;
      and gamma, -63%; n = 6). Subcellular localization of ENaC subunits was not
      altered at week 2. Sgk1 mRNA did not change, whereas Nedd4-2 protein was reduced
      by >50% 2-4 weeks after BDL. NCC protein significantly increased at week 1
      (control vs BDL: +66%, n = 6, P<0.05) and decreased at week 3 (control vs BDL: 
      85%, n = 6, P<0.0005). CONCLUSIONS: Enhanced abundance of NCC was observed in the
      initial stage after BDL, followed by a marked decrease. ENaC transcription,
      translation or cell surface abundance was not increased after BDL.

PMID- 15956071
TI  - Intravenous iron-gluconate during haemodialysis modifies plasma beta2
      microglobulin properties and levels.
AB  - BACKGROUND: Intravenous iron replacement therapy is routinely used for correction
      of anaemia in patients with end-stage renal failure. Free or labile iron, present
      both in parenteral iron formulations and in blood of haemodialysis (HD) patients,
      has the potential to induce severe oxidative processes. This study evaluated the
      acute in vivo effect of intravenous iron administration on the oxidation of
      plasma beta2-microglobulin (beta2m) and on its plasma levels after HD. METHODS:
      Iron-gluconate was administered intravenously to 14 patients receiving HD with
      low-flux cellulose-triacetate membranes during the first hour of the 4 h HD
      treatment. Each patient underwent three different dialysis treatments, during
      which an infusion of 62.5, 125 or 0 mg (control) of iron-gluconate was
      administered in random order. Plasma beta2m levels and iron parameters were
      monitored immediately before and after each HD treatment. The molecular isoforms
      of beta2m were studied by two-dimensional gel electrophoresis and western
      analysis. Levels of oxidized beta2m were evaluated by reaction with 2,4
      dinitrophenylhydrazine and western analysis. RESULTS: Both doses of iron
      gluconate caused remarkable changes in the molecular properties of beta2m,
      including shift in isoelectric point, molecular mass and degree of oxidation.
      Iron administration also limited the decline in plasma beta2m levels to <7.5%,
      compared with 27.9+/-2.7% during HD without iron. CONCLUSIONS: Intravenous iron
      gluconate led to a characteristic increase in molecular weight and in negative
      charge of beta2m, both of which can be assumed to be consistent with reduced
      membrane sieving coefficients and membrane adsorption, and thus with reduced
      clearance of beta2m.

PMID- 15956072
TI  - Close association of Chlamydia pneumoniae IgA seropositivity by ELISA with the
      presence of coronary artery stenosis in haemodialysis patients.
AB  - BACKGROUND: Traditional risk factors of cardiovascular disease do not fully
      explain the accelerated atherosclerosis present in patients with end-stage renal
      disease (ESRD). The goal of this study was to identify the association of
      clinical and laboratory factors including seropositivity for Chlamydia pneumoniae
      determined by a specific enzyme-linked immunosorbent assay (ELISA) with the
      presence of coronary artery disease identified by coronary angiography in ESRD
      patients. METHODS: We prospectively enrolled 161 consecutive ESRD patients
      undergoing haemodialysis for >6 months (106 men, 55 women; mean age 63.1+/-10.2
      years; mean dialysis duration 91.3+/-90.1 months). All patients underwent
      coronary angiography within 1 week after blood sampling. The associations of
      coronary artery disease with clinical parameters including C. pneumoniae IgA and
      IgG seropositivity were analysed using multiple logistic regression models.
      RESULTS: Coronary stenosis >50% was found in 102 of 161 haemodialysis patients
      (63.4%). Of the 102 patients, 75.5% were asymptomatic. Seropositivity for C.
      pneumoniae IgA was found in patients with coronary stenosis (77 out of 102,
      75.5%) more frequently (P<0.001) than in patients without coronary stenosis (10
      out of 59, 16.9%). Seropositivity for C. pneumoniae IgA but not IgG was strongly
      associated with the presence of coronary stenosis in multiple logistic regression
      analysis (odds ratio, 18.440; 95% confidence interval, 7.500-45.337),
      independently of the Framingham coronary risk factors, factors peculiar to ESRD
      or serum C-reactive protein levels. CONCLUSIONS: C. pneumoniae IgA seropositivity
      determined by ELISA is an independent laboratory factor indicating the presence
      of coronary artery stenosis in ESRD patients undergoing maintenance
      haemodialysis.

PMID- 15956073
TI  - Longitudinal follow-up of bone mineral density in children with nephrotic
      syndrome and the role of calcium and vitamin D supplements.
AB  - BACKGROUND: We previously have demonstrated that children with idiopathic
      nephrotic syndrome (INS) are at risk of metabolic bone disease (MBD). In this
      study, we report the longitudinal follow-up of these children and the role of
      calcium and vitamin D supplements. METHODS: We prospectively studied 100
      consecutive children with INS. They were treated with prednisone. All were
      subjected to a baseline clinical, biochemical and radiological evaluation. They
      were initiated on calcium (500 mg/day) and vitamin D3 (200 IU/day) supplements,
      followed by a repeat assessment. The primary outcome measure was the Deltaz score
      (difference between the initial and final z scores) on dual energy X-linked
      absorptiometry (DEXA). A univariate and multivariate analysis using stepwise
      linear regression was performed for factors predictive of an improved Deltaz
      score. RESULTS: Of the 88 children that completed the study, the majority (n =
      54) had improved bone mineral density (BMD) at the spine, and another 25 children
      had stable BMD on calcium and vitamin D3 supplements. The mean spinal BMD values
      were significantly better on follow-up (0.607+/-0.013 g/cm2) as compared with
      baseline values (0.561+/-0.010 g/cm2) (P<0.0001). The interval between initial
      and follow-up assessment was 1.5+/-0.07 years. Children who were on these
      supplements (n = 73) had a significantly improved z score as compared with those
      who did not receive them (n = 15) (P = 0.008). On multivariate analysis, the
      factors predictive of an improved z score were: younger age (P<0.0001), calcium
      and vitamin D3 supplement (P<0.0001), greater dietary calcium intake (P = 0.022)
      and lower interval steroid dose (P = 0.001). CONCLUSIONS: Children with greater
      steroid doses were likely to have low BMD on follow-up. Calcium and vitamin D
      supplements may help in improving BMD in children with INS.

PMID- 15956074
TI  - Partners' concerns, needs and expectations in ESRD: results of the CODIT Study.
AB  - BACKGROUND: The incidence of chronic kidney failure, like that of many chronic
      diseases, is on the increase with most patients today being treated at home.
      METHODS: The CODIT Study, based on a self-report questionnaire returned by 1815
      respondents, set out to assess the impact of this disease and its treatment on
      the lives of patients' partners. RESULTS: Transplantation significantly lightens
      the load on this population, with two in three partners of patients still on
      dialysis judging the overall impact on their own daily life as major, compared
      with only one in four of the partners of transplanted patients. Partners of
      patients on dialysis devote more time to the patient, are more likely to
      experience negative practical, relational, social, psychological and professional
      consequences and they judge their own quality of life as significantly lower than
      do the partners of transplanted patients. Nevertheless, this is not to say that a
      significant fraction of the latter group does not experience profound compromise
      in many areas of life. CONCLUSIONS: This study has identified clear differences
      in outlook and attitudes between dialysis and transplanted patient's partners.
      Quality of life of spouses of transplanted patients was significantly better.
      Indeed transplantation appears often like an outcome. On the contrary, needs in
      both groups were more material than psychological. Having highlighted needs and
      concerns of the spouses, it might be possible to fulfil them in order to optimize
      patient management.

PMID- 15956075
TI  - Clinical review: the strategy of immediate reoperation for transsphenoidal
      surgery for Cushing's disease.
AB  - CONTEXT: Transsphenoidal surgery is currently the primary therapeutic option for
      Cushing's disease. Despite considerable initial success, 10-30% of patients fail
      to achieve lasting remission. EVIDENCE ACQUISITION: We evaluated a strategy of
      immediate reoperation in surgical failures judged by plasma cortisol levels that
      did not fall to 2 microg/dl or less within 72 h of surgery. Of 215 patients with
      presumed ACTH microadenomas, treated between 1993 and 2004, 12 met inclusion
      criteria and had prompt (within 15 d) reoperation for residual or missed ACTH
      microadenoma. These 12 patients represent 28% of those who did not have evidence
      of postoperative adrenal insufficiency. EVIDENCE SYNTHESIS: Based on an outcome
      measure of sustained subnormal or normal plasma cortisol levels, eight of 12
      patients (67%) achieved remission from the two operations. Adjunctive therapies
      (radiotherapy, gamma knife radiosurgery, and adrenalectomy) led to remission in
      another three patients. It is recognized that this outcome required either total
      hypophysectomy (one patient) or postoperative hypopituitarism (all patients in
      remission). CONCLUSION: Magnetic resonance imaging was not usually helpful in
      determining therapeutic strategies; however, inferior petrosal sinus sampling was
      critical in providing confidence that the disease was of pituitary origin. A
      treatment algorithm is recommended, based on this study.

PMID- 15956076
TI  - Osteopontin is colocalized with the adhesion molecule CEACAM1 in the extravillous
      trophoblast of the human placenta and enhances invasion of CEACAM1-expressing
      placental cells.
AB  - CONTEXT: The human placenta is a complex tissue and possesses, through its
      capacity to proliferate and to invade maternal tissue, qualities that are usually
      found in malignant tumors. Osteopontin (OPN) and CEACAM1 may regulate these
      processes. OBJECTIVE: The present study was designed to investigate the
      expression pattern of OPN in the human placental components and to correlate it
      with CEACAM1 expression and function in placental cell invasiveness. DESIGN:
      Immunohistochemistry with an OPN-specific antibody and immunofluorescence were
      performed on normal placental samples to investigate the expression pattern of
      OPN and CEACAM1 in the human placenta. Extravillous trophoblast (EVT) hybridoma
      cells transfected with CEACAM1 and stimulated with OPN were studied using the
      Matrigel invasion assay. RESULTS: All placentae presented very strong expression
      of OPN in the EVT at the invasion front, where it colocalized with CEACAM1. In
      addition, OPN was also present in the villous trophoblast, with strongest
      expression in the cytotrophoblast of the first trimester. Transfection with
      CEACAM1 followed by stimulation with OPN resulted in increased invasiveness of
      EVT hybridoma cells. CONCLUSION: The present study shows the first systematic
      analysis of OPN expression pattern in the human placenta showing strong
      expression in the EVT at the invasion front. Colocalization of OPN with CEACAM1
      in the EVT indicates that they might act together to regulate invasiveness at the
      maternal-fetal interface. Using an in vitro model, we also demonstrated increased
      cellular invasiveness after OPN treatment. We speculate that OPN and CEACAM1 may
      act as a functional complex involved in the regulation of placental invasiveness.

PMID- 15956077
TI  - Parity and the risk of autoimmune thyroid disease: a community-based study.
AB  - CONTEXT: Recent studies have suggested that fetal microchimerism (transplacental
      passage of fetal cells followed by engraftment into maternal tissues) may play a
      role in the pathogenesis of autoimmune thyroid disease. If that is true, then
      parity should be a risk factor for autoimmune thyroid disease. OBJECTIVE: The
      objective of this study was to examine parity as a risk factor for autoimmune
      thyroid disease. DESIGN, SETTING, AND PARTICIPANTS: TSH, thyroid peroxidase
      antibody, and thyroglobulin antibody concentrations were measured on archived
      sera from 1045 female participants in a 1981 community health survey in
      Busselton, Western Australia. OUTCOME MEASURES: Odds ratios (ORs) for positive
      thyroid antibodies (increased concentration of either antibody) or thyroid
      dysfunction (abnormal serum TSH) were used. RESULTS: After adjustment for age,
      women who had previously been pregnant did not have a significantly increased
      risk of positive thyroid antibodies [OR, 1.20; 95% confidence interval (CI), 0.74
      1.97; P = 0.46], raised TSH (OR, 0.93; 95% CI, 0.46-1.87; P = 0.84), or reduced
      TSH (OR, 0.87; 95% CI, 0.33-2.30; P = 0.79) compared with women who had never
      been pregnant. For each additional pregnancy, the OR was 1.02 (95% CI, 0.94-1.11;
      P = 0.57) for positive antibodies, 1.02 (95% CI, 0.91-1.14; P = 0.67) for raised
      TSH, and 1.03 (95% CI, 0.87-1.22; P = 0.73) for reduced TSH. Analysis using
      number of live births gave similar results. The results were similar in younger
      and older women. CONCLUSIONS: Parity is not a risk factor for thyroid
      autoimmunity or thyroid dysfunction. These data do not support a key pathogenic
      role for fetal microchimerism in chronic autoimmune thyroid disease.

PMID- 15956078
TI  - Circulating resistin levels are not associated with fat redistribution, insulin
      resistance, or metabolic profile in patients with the highly active
      antiretroviral therapy-induced metabolic syndrome.
AB  - CONTEXT: The mechanisms underlying the development of the highly active
      antiretroviral therapy (HAART)-induced metabolic syndrome remain to be fully
      elucidated. OBJECTIVE: The objective of this study was to investigate whether the
      adipocyte-secreted hormone, resistin, is associated with anthropometric and
      metabolic abnormalities of the HAART-induced metabolic syndrome. DESIGN, SETTING,
      AND PATIENTS: We conducted a cross-sectional study of 227 HIV-positive patients
      (37 women and 190 men) recruited from the infectious diseases clinics. On the
      basis of history, physical examination, dual-energy x-ray absorptiometry, and
      single-slice computed tomography, patients were classified into four groups: non
      fat redistribution (n = 85), fat accumulation (n = 42), fat wasting (n = 35), and
      mixed fat redistribution (n = 56). MAIN OUTCOME MEASURES: The main outcome
      measures were serum resistin levels and anthropometric and metabolic variables.
      RESULTS: Mean serum resistin levels were not significantly different among
      subjects with fat accumulation, fat wasting, or mixed fat redistribution or
      between these groups and the non-fat redistribution group. We found a weak, but
      significant, positive correlation between resistin and percent total body fat (r
      = 0.20; P < 0.01), total extremity fat (r = 0.18; P < 0.01), and abdominal sc fat
      (r = 0.19; P < 0.01), but not abdominal visceral fat (r = -0.10; P = 0.16) or
      waist to hip ratio (r = -0.05; P = 0.43). When adjustments were made for gender
      (women, 3.92 +/- 2.71 ng/ml; men, 2.96 +/- 2.61 ng/ml; P = 0.05), correlations
      between resistin and the above parameters were no longer significant.
      Importantly, resistin levels were not correlated with fasting glucose, insulin,
      homeostasis model assessment of insulin resistance index, triglycerides, or
      cholesterol levels in the whole group. CONCLUSIONS: Resistin is related to
      gender, but is unlikely to play a major role in the insulin resistance and
      metabolic abnormalities of the HAART-induced metabolic syndrome.

PMID- 15956079
TI  - HRPT2 mutational analysis of typical sporadic parathyroid adenomas.
AB  - CONTEXT: Mutations of HRPT2 are frequent in sporadic parathyroid carcinomas and
      central to their pathogenesis. However, the potential diagnostic utility of HRPT2
      mutation status to distinguish between parathyroid carcinoma and adenoma hinges
      on the frequency of HRPT2 mutations in benign adenomas. Even a low rate of HRPT2
      mutation in adenomas would greatly alter diagnostic specificity, because adenomas
      are far more prevalent than carcinomas. The issue remains open because of the
      limited number of typical adenomas, not subjected to additional selection
      criteria, examined in previous studies. OBJECTIVE/DESIGN/PATIENTS: To determine
      the frequency of HRPT2 somatic mutations in a substantial series of typical,
      sporadic parathyroid adenomas, we directly sequenced coding and flanking splice
      junctional regions of all HRPT2 exons in solitary adenomas from 60 patients.
      RESULTS/CONCLUSIONS: No intragenic HRPT2 mutations were detected, strengthening
      the degree of specificity of HRPT2 mutation as a feature of sporadic parathyroid
      carcinoma as opposed to sporadic adenomas. Our observations encourage additional
      study of the diagnostic potential of HRPT2 in parathyroid neoplasia and support
      the view that HRPT2 inactivation is not an important participant in the
      pathogenesis of typical parathyroid adenomas.

PMID- 15956080
TI  - Extracellular matrix and hormones modulate DAX-1 localization in the human fetal
      adrenal gland.
AB  - CONTEXT: The orphan nuclear receptor DAX-1 is essential for human adrenal cortex
      development and functions as a transcriptional repressor of multiple genes
      implicated in steroidogenic pathways. OBJECTIVE: The aim of this study was to
      investigate the localization of the DAX-1 protein in human fetal adrenal glands
      and to assess whether this protein can be modulated by the extracellular matrix
      and hormones. RESULTS: DAX-1 is localized mainly in the nucleus in the outer
      definitive zone and in the cytoplasm in the fetal zone, whereas the number of DAX
      1 positive cells decreases from the external to the internal portion of the
      gland. When cultured on a collagen or a fibronectin matrix, DAX-1 is localized in
      the nucleus of the definitive cells and exhibits a nucleocytoplasmic distribution
      in the fetal cells. ACTH stimulation induces nuclear localization of DAX-1 in
      fetal cells cultured on collagen without modifying nucleocytoplasmic localization
      on fibronectin. In contrast, angiotensin II induces the protein to be localized
      only in the cytoplasm in fetal cells cultured on either collagen or fibronectin.
      CONCLUSIONS: The localization of DAX-1 is compatible with the known functional
      properties of DAX-1 regarding the steroidogenic activity of adrenal cells.
      Moreover, this study suggests that modulation of DAX-1 localization in the fetal
      adrenal gland by hormones and components of the extracellular matrix may
      represent a mechanism for controlling the expression of steroidogenic enzymes in
      the definitive and fetal zones.

PMID- 15956081
TI  - Decrease and senescence of endothelial progenitor cells in patients with
      preeclampsia.
AB  - BACKGROUND: In preeclampsia, the precise mechanism of impaired vascular function
      is still unclear. We hypothesized that cellular function of circulating
      endothelial progenitor cells (EPCs) might be impaired in patients with
      preeclampsia. OBJECTIVE: The objective of this study was to investigate the
      number and status of cellular senescence of EPCs in the circulation of women with
      preeclampsia. METHODS: Circulating EPCs were cultured from patients with
      preeclampsia (n = 8) and normotensive pregnant women (n = 7). EPC numbers were
      assessed by colony-forming unit (CFU) methodology as previously reported. In
      addition, to assess cellular senescence, we measured endogenous beta
      galactosidase activity. Moreover, we assessed whether the serum level of C
      reactive protein (CRP), a marker for systemic inflammation, was associated with
      cellular impairment of EPCs. RESULTS: The number of circulating EPCs was
      decreased in women with preeclampsia controls (median, 10.0 vs. 34.0 CFU; P <
      0.01). The rate of cellular senescence was significantly increased in patients
      with preeclampsia (33.9%) compared with that in controls (22.9%; P < 0.05).
      Patients with preeclampsia were divided into two subgroups: the CRP-negative
      group (CRP, <0.1 mg/dl; n = 4) and the CRP-positive group (CRP, > or =0.1 mg/dl;
      n = 4). Interestingly, EPC CFU counts were markedly decreased in CRP-positive
      patients compared with those in CRP-negative patients (5.0 and 25.0 CFU,
      respectively; P < 0.05). Median values for cellular senescence were greater in
      the CRP-positive group than in the CRP-negative group, although this did not
      achieve statistical significance (43.5% and 33.3%, respectively; P = 0.12).
      CONCLUSION: Depletion and cellular aging of EPCs in patients with preeclampsia
      might be associated with endothelial dysfunction and could be affected by
      systemic inflammation.

PMID- 15956082
TI  - Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter)
      syndrome.
AB  - CONTEXT: Klinefelter syndrome (KS; 47,XXY karyotype and variants) is
      characterized by tall stature and testicular failure, with marked variation in
      severity of the phenotype. Previous studies have proposed that genetic factors
      including mosaicism, parental origin of the supernumerary X-chromosome, skewed X
      inactivation, and androgen receptor (AR) polyglutamine repeat length may
      contribute to phenotypic variability in KS. OBJECTIVE: The objective of this
      study was to investigate the roles of these genetic factors in the variability of
      the KS phenotype. DESIGN: This was a cross-sectional study. SETTING: The study
      was performed at a pediatric endocrinology referral clinic. PATIENTS: Thirty-five
      KS boys and men, aged 0.1-39 yr, were studied. INTERVENTIONS: There were no
      interventions. MAIN OUTCOME MEASURES: Auxological measurements, biological
      indices of testicular function, and clinical assessment of muscle tone were the
      main outcome measures. Genetic studies included karyotyping to detect mosaicism,
      genotyping of microsatellite markers to determine parental origin of the
      supernumerary X-chromosome, and genotyping and methylation studies to measure AR
      polyglutamine (AR CAGn) repeat length and X inactivation ratio. RESULTS: The only
      genetic factor that significantly influenced the KS phenotype was the AR CAGn
      repeat length, which was inversely correlated with penile length, a biological
      indicator of early androgen action. Mosaicism, imprinting, and skewed X
      inactivation did not account for the variability of the KS phenotype.
      CONCLUSIONS: Normal genetic variation in the AR coding sequence may be clinically
      significant in the setting of early testicular failure and subnormal circulating
      testosterone levels, as occur in KS.

PMID- 15956083
TI  - Pancreastatin: multiple actions on human intermediary metabolism in vivo,
      variation in disease, and naturally occurring functional genetic polymorphism.
AB  - RATIONALE: The chromogranin A (CHGA) fragment pancreastatin (human CHGA250-301)
      impairs glucose metabolism, but the role of human pancreastatin in vivo remains
      unexplored. METHODS: We studied brachial arterial infusion of pancreastatin
      (CHGA273-301-amide at approximately 200 nm) on forearm metabolism of glucose,
      free fatty acids, and amino acids. Plasma pancreastatin was measured in obesity
      or type 2 diabetes. Systematic discovery of amino acid variation was performed,
      and the potency of one variant in the active carboxyl terminus (Gly297Ser) was
      tested. RESULTS: Pancreastatin decreased glucose uptake by approximately 48-50%;
      the lack of change in forearm plasma flow indicated a metabolic, rather than
      hemodynamic, mechanism. A control CHGA peptide (catestatin, CHGA352-372) did not
      affect glucose. Insulin increased glucose uptake, but pancreastatin did not
      antagonize this action. Pancreastatin increased spillover of free fatty acids by
      about 4.5- to 6.4-fold, but not spillover of amino acids. Insulin diminished
      spillover of both free fatty acids and amino acids, but these actions were not
      reversed by pancreastatin. Plasma pancreastatin was elevated approximately 3.7
      fold in diabetes, but was unchanged during weight loss. Proteolytic cleavage
      sites for pancreastatin in vivo were documented by matrix-assisted laser
      desorption ionization/time of flight mass spectrometry. Three pancreastatin
      variants were discovered: Arg253Trp, Ala256Gly, and Gly297Ser. The Gly297Ser
      variant had unexpectedly increased potency to inhibit glucose uptake.
      CONCLUSIONS: The dysglycemic peptide pancreastatin is specifically and potently
      active in humans on multiple facets of intermediary metabolism, although it did
      not antagonize insulin. Pancreastatin is elevated in diabetes, and the variant
      Gly297Ser had increased potency to inhibit glucose uptake. The importance of
      human pancreastatin in vivo as well as its natural variants is established.

PMID- 15956084
TI  - High fetal urocortin levels at term and preterm labor.
AB  - CONTEXT: Placental urocortin has a role in the cascade of events leading to
      parturition by stimulating myometrial contractility and placental uterotonins
      secretion. OBJECTIVE: The objective of this study was to evaluate urocortin
      levels in maternal and fetal [umbilical cord artery (UCA) and vein (UCV)] plasma
      at term and preterm labor. DESIGN: The study design was a controlled cross
      sectional study performed from November 2003 to June 2004. SETTING: This study
      was performed at the Division of Obstetrics and Gynecology, University of Siena
      (Siena, Italy). PATIENTS: Plasma samples were collected at term in the absence of
      labor (TNL; n = 27; 39.3 +/- 0.1 gestational weeks), at term spontaneous vaginal
      delivery (TL; n = 24; 40.1 +/- 0.2 gestational weeks), and at preterm labor (PTL;
      n = 19; 32.4 +/- 0.4 gestational weeks). Changes in urocortin mRNA expression
      were also evaluated in placentas collected from TNL (n = 11), TL (n = 11), and
      PTL (n = 10). INTERVENTION: Urocortin levels were measured by specific RIA.
      Changes in placental mRNA expression were determined by real-time quantitative RT
      PCR analysis. RESULTS: Maternal and UCA plasma urocortin levels were
      significantly (P < 0.0001 for all) higher in TL and PTL than in TNL. Furthermore,
      UCA concentrations were significantly (P < 0.0001 for all) higher than and
      correlated with maternal concentrations (TNL: r = 0.45; P < 0.05; TL: r = 0.959;
      P < 0.0001; PTL: r = 0.7719; P < 0.0001). UCV levels were significantly (P <
      0.001) higher in TL and PTL than in TNL and were significantly (P < 0.0001 for
      all) higher than and significantly (P < 0.0001 for all) correlated with maternal
      values, but were significantly (P < 0.0001 for all) lower than and correlated
      with UCA values (TNL: r = 0.9548; P < 0.0001; TL: r = 0.927; P < 0.0001; PTL: r =
      0.838; P < 0.0001). Placental urocortin mRNA expression did not differ among TNL,
      TL, and PTL samples. CONCLUSIONS: Fetal urocortin secretion is increased in term
      and preterm labor. Whether these changes are a consequence rather than a cause of
      human parturition remains to be addressed.

PMID- 15956085
TI  - PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) mutations and response
      to growth hormone therapy in children with Noonan syndrome.
AB  - CONTEXT: The cause of growth impairment in Noonan syndrome (NS) remains unclear.
      Mutations in PTPN11 (protein tyrosine phosphatase, nonreceptor type 11) that
      codify constitutively activated Src homology protein tyrosine phosphatase-2
      tyrosine phosphatase and may interfere with GH and IGF-I signaling were
      identified in approximately 40% of patients with NS. OBJECTIVE: The objective of
      this study was to evaluate the influence of PTPN11 status on response to human GH
      (hGH) treatment in NS children with short stature. SETTING: This study was
      performed at a university hospital. DESIGN: The study design was to conduct a
      retrospective analysis of 3 yr of hGH treatment and genotyping of PTPN11 in
      patients with NS. PATIENTS: Fourteen NS patients, half of them with PTPN11
      mutations in heterozygous state, were studied. At the beginning of treatment,
      there were no clinical or laboratory differences between groups with and without
      mutations in the PTPN11 gene. INTERVENTION: Patients were treated with hGH (47
      microg/kg.d). MAIN OUTCOME MEASURES: The main outcome measures were PTPN11
      genotype, change in IGF-I levels, and change in height sd score. RESULTS:
      Patients with mutations in PTPN11 presented a significantly smaller increment in
      IGF-I levels during the treatment compared with patients without mutations (86 +/
      67 and 202 +/- 93 microg/liter, respectively; P = 0.03). hGH treatment
      significantly improved growth velocity in both groups, with slightly better
      results observed in patients without mutations. This was translated into greater
      gains in height sd score relation to baseline during the 3 yr of treatment in
      patients without mutations (+1.7 +/- 0.1) compared with those with mutations
      (+0.8 +/- 0.4; P < 0.01). CONCLUSIONS: Our findings suggest that the presence of
      PTPN11 mutations in patients with NS indicates a reduced growth response to long
      term hGH treatment.

PMID- 15956086
TI  - Acute pressor and hormonal effects of beta-endorphin at high doses in healthy and
      hypertensive subjects: role of opioid receptor agonism.
AB  - CONTEXT: The opioid system is involved in blood pressure regulation in both
      normal humans and patients with essential hypertension. OBJECTIVE: The objective
      of the study was to investigate the effects of a high-dose infusion of beta
      endorphin, an opioid peptide, on blood pressure and on the hormonal profile in
      healthy subjects and in hypertensive patients and the mediation played by opioid
      receptor agonism. DESIGN, SETTING, AND PARTICIPANTS: According to a randomized
      double-blind design, 11 healthy subjects (controls) and 12 hypertensive
      inpatients (mean age, 38.9 and 40.4 yr, respectively) received 1-h iv infusion of
      beta-endorphin (250 mug/h) and, on another occasion, the same infusion protocol
      preceded by the opioid antagonist naloxone (8 mg). MAIN OUTCOME MEASURES:
      Hemodynamic and hormonal measurements were performed at established times during
      the infusion protocols. RESULTS: At baseline, circulating beta-endorphin,
      norepinephrine, and endothelin-1 in hypertensive patients were significantly (P <
      0.05) higher than in controls. In controls, beta-endorphin reduced blood pressure
      (P < 0.01) and circulating norepinephrine (P < 0.02) and increased plasma atrial
      natriuretic factor (P < 0.003) and GH (P < 0.0001). In hypertensive patients,
      beta-endorphin decreased systemic vascular resistance (P < 0.0001), blood
      pressure (P < 0.0001), and plasma norepinephrine (P < 0.0001) and endothelin-1 (P
      < 0.0001) and raised circulating atrial natriuretic factor (P < 0.0001), GH (P <
      0.0001), and IGF-I (P < 0.0001). These hemodynamic and hormonal responses to beta
      endorphin in hypertensive patients were significantly (P < 0.0001) greater than
      in controls but were annulled in all individuals when naloxone preceded beta
      endorphin infusion. CONCLUSIONS: High doses of beta-endorphin induce hypotensive
      and beneficial hormonal effects in humans, which are enhanced in essential
      hypertension and are mediated by opioid receptors.

PMID- 15956087
TI  - Increased density of ghrelin-expressing cells in the gastric fundus and body in
      Prader-Willi syndrome.
AB  - CONTEXT: The levels of ghrelin, an orexigenic hormone secreted by oxyntic cells
      in the digestive tract, are elevated in Prader-Willi syndrome (PWS) and GH
      deficiency (GHD) patients. In this study, we hypothesized that the
      hyperghrelinemia observed in PWS is related to IGF-I or GH/IGF axis deficiency.
      DESIGN: We investigated the densities of ghrelin-expressing cells (GECs), the
      amounts of ghrelin in gastric tissues, and ghrelin levels in plasma in 16 PWS
      patients and compared these results with those of 13 GHD patients and comparison
      groups (19 normal lean and 10 normal obese subjects). RESULTS: In the gastric
      body and fundus, 2- to 3-fold increases in the numbers of GECs (P < 0.001) and in
      the amounts of ghrelin (P < 0.018) were noted in PWS patients vs. comparison
      groups, whereas GEC numbers in GHD patients were similar to those of the
      comparison group despite elevated fasting plasma ghrelin levels. In addition, IGF
      I sd scores in PWS were not found to be correlated with GEC densities, the
      amounts of ghrelin expressed in gastric tissues, or plasma ghrelin levels.
      CONCLUSIONS: Our results suggest that IGF-I or GH/IGF axis deficiency appears to
      be unrelated to observed GEC increases in the stomach of patients with PWS.

PMID- 15956088
TI  - Lack of recording of systemic lupus erythematosus in the death certificates of
      lupus patients.
AB  - OBJECTIVE: To determine to what extent the diagnosis of systemic lupus
      erythematosus (SLE) in deceased lupus patients is under-reported in death
      certificates, and the patient characteristics associated with such an occurrence.
      METHODS: The death certificates of 76 of the 81 deceased SLE patients from two US
      lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for
      Carolina Lupus Study), including 570 and 265 patients, respectively, were
      obtained from the Offices of Vital Statistics of the states where the patients
      died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas).
      Both cohorts included patients with SLE as per the American College of
      Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of <
      or =5 yr. The median duration of follow-up in each cohort at the time of these
      analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were
      performed comparing patients with SLE recorded anywhere in the death certificate
      and those without it. A multivariable logistic regression model was performed to
      identify the variables independently associated with not recording SLE in death
      certificates. RESULTS: In 30 (40%) death certificates, SLE was not recorded
      anywhere in the death certificate. In univariable analyses, older age was
      associated with lack of recording of SLE in death certificates [mean age
      (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom
      SLE was omitted and included on the death certificates, respectively, P = 0.005].
      Patients without health insurance, those dying of a cardiovascular event and
      those of Caucasian ethnicity were also more likely to be in the non-recorded
      group. In the multivariable analysis, variables independently associated with not
      recording SLE as cause of death were older age [odds ratio = (95% confidence
      interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health
      insurance [4.649 (1.152-18.768); P = 0.031]. CONCLUSIONS: A high proportion of
      SLE diagnoses are not recorded in death certificates. Older patients and those
      without health insurance are more prone to have SLE not recorded. These findings
      do have implications for the assessment of the impact of this disease in
      epidemiological studies conducted using vital statistics records.

PMID- 15956089
TI  - Re: Aouba et al. Crowned dens syndrome misdiagnosed as polymyalgia rheumatica,
      giant cell arteritis, meningitis or spondylitis.

PMID- 15956090
TI  - Primary Sjogren's syndrome: current and emergent aetiopathogenic concepts.

PMID- 15956091
TI  - Does systemic-onset juvenile idiopathic arthritis belong under juvenile
      idiopathic arthritis?
AB  - 'Science is the systematic classification of experience' George Henry Lewes (1817
      78), English philosopher, critic, dramatist, scientist. Juvenile idiopathic
      arthritis (JIA) is prevalent in about 1 in 1000 children. The earliest formal
      description of this disease was by Sir George Frederick Still in 1897. This work
      was done when he was a registrar at the Hospital for Sick Children, Great Ormond
      Street, London. In this initial description of 19 patients he identified three
      patterns of arthritis, one of which came to be known later as Still's disease
      [now known as systemic-onset juvenile idiopathic arthritis (SoJIA)]. Over the
      next few decades it came to be appreciated that one form of arthritis in children
      is very different and dominated by the presence of systemic manifestations. Over
      the last two decades several paediatric rheumatologists have come together to
      classify juvenile arthritis for purposes of better disease identification and
      research. All along, the systemic form of juvenile arthritis was always
      recognized as belonging to a distinct group; in fact for several decades (and
      even now in some countries) the systemic form of juvenile arthritis was referred
      to as Still's disease. In this article we will attempt to highlight the reasons
      why we feel that SoJIA is perhaps not best retained in the company of JIA.

PMID- 15956092
TI  - Symptomatic renal tubular acidosis (RTA) in patients with systemic lupus
      erythematosus: an analysis of six cases with new association of type 4 RTA.
AB  - OBJECTIVES: We have analysed the association between different parameters of
      renal tubular acidosis (RTA) with clinical and laboratory parameters in patients
      with systemic lupus erythematosus (SLE). METHODS: Review of hospital database
      records between 1978 and 2003 revealed six SLE patients with RTA. Correlations
      and comparisons were done by Spearman rank correlation coefficient and the chi(2)
      test. RESULTS: Four patients had hypokalaemia (type 1 RTA) and two patients had
      hyperkalaemia (type 4 RTA). Three patients with type 1, but no patients with type
      4 RTA, had medullary nephrocalcinosis. The majority of SLE patients with distal
      RTA (type 1 and type 4) had nephritis with proteinuria. No seronegative SLE was
      noted, and all patients were negative for anticardiolipin antibodies. There was a
      noticeable trend of higher serum potassium levels with increased SLE Disease
      Activity Index (SLEDAI; P < 0.1) and nephritic manifestation (haematuria, P <
      0.1). The mean SLEDAI scores were 11.75 and 27.5 for type 1 and type 4 RTA
      patients, respectively. CONCLUSIONS: When present in patients with SLE, classic
      distal RTA (type 1) is the most common. In particular, we report here for the
      first time two cases of type 4 RTA in SLE patients with higher SLEDAI scores than
      patients with type 1 RTA. Medullary nephrocalcinosis or renal urolithiasis has
      not been found in our patients with type 4 RTA. Higher serum potassium levels
      seem to be associated with higher SLEDAI scores and more severe nephritic
      manifestations in patients with distal RTA.

PMID- 15956093
TI  - Modelling the effect of function and disease activity on costs and quality of
      life in rheumatoid arthritis.
AB  - OBJECTIVE: When treatments with the potential to change the natural history of a
      disease are introduced, their longer-term effect on costs and quality of life
      (utility) has to be estimated using economic models. However, to remain useful
      tools, models must be updated when new information becomes available. Our earlier
      models in rheumatoid arthritis (RA) have been based on functional status, but it
      has recently been shown that disease activity might have an independent effect on
      utility. The objective of this study was to improve the model by incorporating
      the effect of a subjective measure of disease severity and activity (global VAS).
      METHODS: A Markov model was constructed with five states according to functional
      status (HAQ), and each state was subdivided according to the VAS (<40 and >40).
      Disease development (transition probabilities between the states) was taken from
      a longitudinal cohort study of patients with early RA in Sweden. A recent
      population-based survey of 616 patients with RA provided data on costs and
      utilities. The model incorporates the full distribution of costs and utilities
      from the survey, and long-term projections are made using Monte Carlo simulation.
      RESULTS: The global VAS had a highly significant effect on utilities
      independently of HAQ. For resource consumption, only HAQ was a significant
      predictor, with the exception of sick leave, which was correlated with the VAS
      but not with HAQ. Using the cohort distribution from the longitudinal study,
      expected mean costs per patient over 10 yr were 106 034 euros (s.d. 5091 euros)
      (1 euro = SEK 9.20) and the expected number of quality-adjusted life years
      (QALYs) was 5.08 (s.d. 0.09). Patients starting at HAQ <0.6 but with consistently
      high VAS scores would have expected costs of 102 830 euros and 4.96 QALYs, while
      patients with low VAS scores would have costs of 81 603 euros and 6.01 QALYs.
      CONCLUSION: Our new model incorporates for the first time the effect of a
      subjective measure of disease severity and activity on both costs and utility,
      making it a sensitive tool to estimate the cost-effectiveness of disease
      modifying treatments. New data on resource consumption indicate a shift to higher
      direct costs, particularly in early disease, and lower indirect costs in more
      advanced disease. The large size of the data sets used in this model reduces the
      uncertainty and makes estimates very stable.

PMID- 15956094
TI  - Mechanisms of inflammation in gout.

PMID- 15956095
TI  - Neonatal cranial ultrasound versus MRI and neurodevelopmental outcome at school
      age in children born preterm.
AB  - AIM: To examine the correlation between neonatal cranial ultrasound and school
      age magnetic resonance imaging (MRI) and neurodevelopmental outcome. METHODS: In
      a prospective 2 year cohort study, 221 children (gestational age < or =32 weeks
      and/or birth weight < or =1500 g) participated at a median age of 8.1 years
      (inclusion percentage 78%). Conventional MRI, IQ (subtests of the WISC), and
      motor performance (Movement Assessment Battery for Children) at school age were
      primary outcome measurements. RESULTS: Overall, there was poor correspondence
      between ultrasound group classifications and MRI group classifications, except
      for the severe group (over 70% agreement). There was only a 1% chance of the
      children with a normal cranial ultrasound having a major lesion on MRI. Mean IQ
      (standard deviation) was significantly lower in children with major ultrasound or
      MRI lesions, but was also lower in children with minor lesions on MRI compared to
      children with a normal MRI (91+/-16, 100+/-13, 104+/-13 for major lesions, minor
      lesions, and normal MRI, respectively). Median total impairment score (TIS) was
      significantly higher in children with major lesions on ultrasound or MRI as well
      as in children with minor lesions on MRI (TIS 4.0 and 6.25 for normal and minor
      lesions on MRI, respectively; p<0.0001). CONCLUSIONS: A normal neonatal cranial
      ultrasound excluded a severe lesion on MRI in 99% of cases. MRI correlated more
      strongly with mean IQ and median TIS than ultrasound. Subtle white matter lesions
      are better detected with MRI which could explain the stronger correlation of MRI
      with IQ and motor performance.

PMID- 15956096
TI  - Cognitive development in low risk preterm infants at 3-4 years of life.
AB  - BACKGROUND: Major neurological handicaps and neuropsychological disturbances are
      more common in ex-preterm children than their counterparts born at term.
      OBJECTIVE: To establish in a prospective study whether a characteristic
      neuropsychological profile exists in ex-preterm children who do not exhibit
      neurodevelopmental deficits on routine clinical examination. METHODS: Thirty
      intellectually normal children born preterm (30-34 weeks gestation) without major
      neurological disabilities and a control group of term children matched for age,
      sex, and parental educational and occupational status were assessed at 3-4 years
      of age to obtain a complete neuropsychological profile. Intellectual ability,
      language comprehension and expression, perceptual and visual motor function,
      working memory, and attention and behavioural problems were investigated.
      RESULTS: Even in the absence of major neurological signs, children born preterm
      achieved lower mean scores than controls on the Stanford-Binet intelligence scale
      (110.8 v 121, p<0.001), visual perception test (33.8 v 42.7, p<0.001), visual
      motor integration test (42.6 v 47.4, p = 0.049), memory for location test (8.4 v
      9.5, p = 0.007), sustained attention test (41.6 v 51.5, p = 0.009), and the
      picture vocabulary test (33.3 v 44.7, p = 0.021). CONCLUSIONS: Neuropsychological
      abnormalities can be detected early in childhood in apparently normal ex-preterm
      children and are consistent with a growing body of evidence that prematurity may
      be associated with long term neuropsychological morbidity in childhood and
      adolescence.

PMID- 15956097
TI  - Linezolid: low pre-treatment platelet values could increase the risk of
      thrombocytopenia.

PMID- 15956098
TI  - Ciprofloxacin resistance among human Campylobacter isolates 1991-2004: an update.

PMID- 15956099
TI  - Effect of subinhibitory concentrations of ciprofloxacin on Mycobacterium
      fortuitum mutation rates.
AB  - OBJECTIVES: Fluoroquinolones have found a place in the management of
      mycobacterial diseases including tuberculosis. It has been previously shown that
      subinhibitory concentrations of quinolones increase the mutation rate in
      Escherichia coli and staphylococci. The purpose of this study is to extend this
      observation to mycobacteria and to quantify mutation rates. METHODS: The mutation
      rate in Mycobacterium fortuitum to ciprofloxacin, levofloxacin, moxifloxacin,
      rifampicin, erythromycin and gentamicin resistance was determined when grown with
      and without various sub-MIC concentrations of ciprofloxacin. RESULTS: M.
      fortuitum exposed to 1/2 MIC ciprofloxacin had an increase in the mutation rate
      of between 72- and 120-fold when selected on quinolones or other
      antimycobacterial antibiotics. Smaller, but significant increases in mutation
      rate were seen when the organism was exposed to lower concentrations (1/4 MIC and
      1/8 MIC). CONCLUSIONS: These data show that sub-MIC concentrations of
      fluoroquinolone significantly increase mutation rates and these data suggest that
      care must be taken to ensure that bacteria are not exposed to subinhibitory
      concentrations when adding quinolones to a regimen used to treat mycobacterial
      infection.

PMID- 15956100
TI  - Fluoroquinolone treatment of experimental Salmonella enterica serovar Typhimurium
      DT104 infections in chickens selects for both gyrA mutations and changes in
      efflux pump gene expression.
AB  - OBJECTIVES: To determine the efficacy of enrofloxacin (Baytril) in chickens in
      eradicating three different resistance phenotypes of Salmonella enterica and to
      examine the resistance mechanisms of resulting mutants. METHODS: In two separate
      replicate experiments (I and II), three strains of Salmonella enterica serovar
      Typhimurium DT104 [strain A, fully antibiotic-sensitive strain; strain B,
      isogenic multiple antibiotic-resistant (MAR) derivative of A; strain C,
      veterinary penta-resistant phenotype strain containing GyrA Phe-83], were
      inoculated into day-old chicks at approximately 10(3) cfu/bird. At day 10, groups
      of chicks (n =10) were given either enrofloxacin at 50 ppm in their drinking
      water for 5 days or water alone (control). Caecal contents were monitored for
      presence of Salmonella and colonies were replica plated to media containing
      antibiotics or overlaid with cyclohexane to determine the proportion of isolates
      with reduced susceptibility. The MICs of antibiotics and cyclohexane tolerance
      were determined for selected isolates from the chicks. Mutations in topoisomerase
      genes were examined by DHPLC and expression of marA, soxS, acrB, acrD and acrF by
      RT-PCR. RESULTS: In experiment I, but not II, enrofloxacin significantly reduced
      the numbers of strain A compared with the untreated control group. In experiment
      II, but not I, enrofloxacin significantly reduced the numbers of strain B.
      Shedding of strain C was unaffected by enrofloxacin treatment. Birds infected
      with strains A and B gave rise to isolates with decreased fluoroquinolone
      susceptibility. Isolates derived from strain A or B requiring >128 mg/L nalidixic
      acid for inhibition contained GyrA Asn-82 or Phe-83. Isolates inhibited by 16
      mg/L nalidixic acid were also less susceptible to antibiotics of other chemical
      classes and became cyclohexane-tolerant (e.g. MAR). CONCLUSIONS: These studies
      demonstrate that recommended enrofloxacin treatment of chicks rapidly selects for
      strains with reduced fluoroquinolone susceptibility from fully sensitive and MAR
      strains. It can also select for MAR isolates.

PMID- 15956101
TI  - Real-time monitoring of enzymatic DNA hydrolysis by electrospray ionization mass
      spectrometry.
AB  - A fast and direct method for the monitoring of enzymatic DNA hydrolysis was
      developed using electrospray ionization mass spectrometry. We incorporated the
      use of a robotic chip-based electrospray ionization source for increased
      reproducibility and throughput. The mass spectrometry method allows the detection
      of DNA fragments and intact non-covalent protein-DNA complexes in a single
      experiment. We used the method to monitor in real-time single-stranded (ss) DNA
      hydrolysis by colicin E9 DNase and to characterize transient non-covalent E9
      DNase-DNA complexes present during the hydrolysis reaction. The mass spectra
      showed that E9 DNase interacts with ssDNA in the absence of a divalent metal ion,
      but is strictly dependent on Ni2+ or Co2+ for ssDNA hydrolysis. We demonstrated
      that the sequence selectivity of E9 DNase is dependent on the ratio protein:ssDNA
      or the ssDNA concentration and that only 3'-hydroxy and 5'-phosphate termini are
      produced. It was also shown that the homologous E7 DNase is reactive with Zn2+ as
      transition metal ion and that this DNase displays a different sequence
      selectivity. The method described is of general use to analyze the reactivity and
      specificity of nucleases.

PMID- 15956102
TI  - Structure of RadB recombinase from a hyperthermophilic archaeon, Thermococcus
      kodakaraensis KOD1: an implication for the formation of a near-7-fold helical
      assembly.
AB  - The X-ray crystal structure of RadB from Thermococcus kodakaraensis KOD1, an
      archaeal homologue of the RecA/Rad51 family proteins, have been determined in two
      crystal forms. The structure represents the core ATPase domain of the RecA/Rad51
      proteins. Two independent molecules in the type 1 crystal were roughly related by
      7-fold screw symmetry whereas non-crystallographic 2-fold symmetry was observed
      in the type 2 crystal. The dimer structure in the type 1 crystal is extended to
      construct a helical assembly, which resembles the filamentous structures reported
      for other RecA/Rad51 proteins. The molecular interface in the type 1 dimer is
      formed by facing a basic surface patch of one monomer to an acidic one of the
      other. The empty ATP binding pocket is located at the interface and barely
      concealed from the outside similarly to that in the active form of the RecA
      filament. The model assembly has a positively charged belt on one surface
      bordering the helical groove suitable for facile binding of DNA. Electron
      microscopy has revealed that, in the absence of ATP and DNA, RadB forms a
      filament with a similar diameter to that of the hypothetical assembly, although
      its helical properties were not confirmed.

PMID- 15956104
TI  - Management of referred deep brain stimulation failures: a retrospective analysis
      from 2 movement disorders centers.
AB  - BACKGROUND: Since the Food and Drug Administration approved DBS, there has been a
      surge in the number of centers providing the procedure. There is currently no
      consensus regarding appropriate screening procedures, necessary training of
      individuals providing the therapy, the need for an interdisciplinary team, or
      guidelines for the management of complications. An increasing number of patients
      come to experienced DBS centers after unsatisfactory results from DBS surgery. An
      attempt is made herein to evaluate the reasons for DBS failure in a series of
      such patients and to make recommendations to improve overall DBS outcomes.
      OBJECTIVE: To improve outcomes of deep brain stimulation (DBS) surgery by
      analyzing a series of patients who had suboptimal results from DBS. METHODS:
      Forty-one consecutive patients complaining of suboptimal results from DBS surgery
      came to the University of Florida Movement Disorders Center, or to Beth Israel
      Movement Disorders Center, over a 24-month period. All patients had undergone
      implantation of DBS devices at outside medical centers. Each patient was
      evaluated by a movement disorders neurologist, and the complete medical record
      was reviewed. The DBS device for each patient was interrogated for adverse
      effects and programmed for maximal benefit. Postoperative imaging studies were
      evaluated whenever possible. RESULTS: The average age of patients was 63.4 years
      (range, 49-84 years). The indication for surgery (by record review) included 9
      patients with essential tremor, 31 with Parkinson disease, and 1 with dystonia.
      The diagnoses after referral examination included 5 with essential tremor, 26
      with Parkinson disease, 3 with Parkinson disease and dementia, 1 with Parkinson
      disease and essential tremor, 1 with corticobasal degeneration, 1 with dystonia,
      2 with multiple system atrophy, 1 with progressive supranuclear palsy, and 1 with
      myoclonus. Issues related to inadequate preoperative screening: Thirty (73%) of
      41 patients saw a movement disorders specialist prior to DBS implantation.
      Fourteen (34%) patients had neuropsychological testing, 4 (10%) did not have
      testing, and in 23 cases (56%), it could not be determined whether or not they
      were tested. Five (12%) of 41 patients had an inadequate medication trial, and 5
      patients (12%) had significant cognitive dysfunction prior to their DBS
      implantation. Surgical and device-related complications: Nineteen (46%) of 41
      patients had suboptimally placed electrodes. Seven electrodes (17%) were replaced
      with improvement. Three patients' devices had failed due to end of battery life,
      2 had infections, and 1 had a fractured lead. Programming and medication
      adjustments: Seven (17%) of 41 patients had no or poor access to programming. Two
      patients (5%) moved, and 2 physicians (5%) moved, creating issues with access to
      care. Eight patients (20%) required local follow-up (they flew to remote centers
      to have the surgery performed). Fifteen patients (37%) were inadequately
      programmed and improved significantly with reprogramming. Six patients (15%)
      experienced partial improvement with reprogramming, and 21 patients (51%) failed
      to improve despite extensive reprogramming. Thirty patients (73%) benefited from
      medication changes, 4 (10%) had antidepressants added to their regimens, and 1
      (2%) had donepezil hydrochloride added. One patient's carbidopa/levodopa (2%) was
      restarted after complete discontinuation. OUTCOMES: With the various
      postoperative interventions described, 21 (51%) of 41 patients had good outcomes,
      6 (15%) had modest clinical improvement, and 14 (34%) did not improve.
      CONCLUSIONS: With appropriate intervention, 51% of patients who complained of
      "failed" DBS procedures ultimately had good outcomes. Thirty-four percent of
      these patients had persistently poor outcomes despite maximal intervention. This
      case series provides important insights into reasons for "DBS failure" and
      proposes strategies to manage patients with DBS more effectively.

PMID- 15956103
TI  - Loss of G-A base pairs is insufficient for achieving a large opening of U4 snRNA
      K-turn motif.
AB  - Upon binding to the 15.5K protein, two tandem-sheared G-A base pairs are formed
      in the internal loop of the kink-turn motif of U4 snRNA (Kt-U4). We have reported
      that the folding of Kt-U4 is assisted by protein binding. Unstable interactions
      that contribute to a large opening of the free RNA ('k-e motion') were identified
      using locally enhanced sampling molecular dynamics simulations, results that
      agree with experiments. A detailed analysis of the simulations reveals that the k
      e motion in Kt-U4 is triggered both by loss of G-A base pairs in the internal
      loop and backbone flexibility in the stems. Essential dynamics show that the loss
      of G-A base pairs is correlated along the first mode but anti-correlated along
      the third mode with the k-e motion. Moreover, when enhanced sampling was confined
      to the internal loop, the RNA adopted an alternative conformation characterized
      by a sharper kink, opening of G-A base pairs and modified stacking interactions.
      Thus, loss of G-A base pairs is insufficient for achieving a large opening of the
      free RNA. These findings, supported by previously published RNA structure probing
      experiments, suggest that G-A base pair formation occurs upon protein binding,
      thereby stabilizing a selective orientation of the stems.

PMID- 15956106
TI  - Body mass index and ambulatory blood pressure monitoring.

PMID- 15956107
TI  - Differential effects of angiotensin II type-1 receptor antisense oligonucleotides
      on renal function in spontaneously hypertensive rats.
AB  - The effect of selectively decreasing renal angiotensin II type 1 (AT1) receptor
      expression on renal function and blood pressure has not been determined.
      Therefore, we studied the consequences of selective renal inhibition of AT1
      receptor expression in normotensive Wistar-Kyoto rats (WKY) and spontaneously
      hypertensive rats (SHR) in vivo. Vehicle, AT1 receptor antisense
      oligodeoxynucleotides (AS-ODN), or scrambled oligodeoxynucleotides were infused
      chronically into the cortex of the remaining kidney of conscious,
      uninephrectomized WKY and SHR on a 4% NaCl intake. Basal renal cortical membrane
      AT1 receptor protein was greater in SHR than in WKY. In WKY and SHR, AS-ODN
      decreased renal but not cardiac AT1 receptors. AT1 receptor AS-ODN treatment
      increased plasma renin activity to a greater extent in WKY than in SHR. However,
      plasma angiotensin II and aldosterone were increased by AS-ODN to a similar
      degree in both rat strains. In SHR, sodium excretion was increased and sodium
      balance was decreased by AS-ODN but had only a transient ameliorating effect on
      blood pressure. Urinary protein and glomerular sclerosis were markedly reduced by
      AS-ODN-treated SHR. In WKY, AS-ODN had no effect on sodium excretion, blood
      pressure, or renal histology but also modestly decreased proteinuria. The major
      consequence of decreasing renal AT1 receptor protein in the SHR is a decrease in
      proteinuria, probably as a result of the amelioration in glomerular pathology but
      independent of systemic blood pressure and circulating angiotensin II levels.

PMID- 15956109
TI  - Aldosterone promotes endothelial dysfunction via prostacyclin independent of
      hypertension.

PMID- 15956108
TI  - Participation of prostacyclin in endothelial dysfunction induced by aldosterone
      in normotensive and hypertensive rats.
AB  - The aim of the present study was to analyze the possible involvement of
      vasoconstrictors prostanoids on the reduced endothelium-dependent relaxations
      produced by chronic administration of aldosterone in Wistar Kyoto rats (WKY) and
      spontaneously hypertensive rats (SHR). For this purpose, acetylcholine (ACh)
      relaxations in aortic segments from both strains were analyzed in absence and
      presence of the cyclooxygenase-1 (COX-1) and COX-2 inhibitor indomethacin, the
      specific COX-2 inhibitor NS-398, the TP receptor antagonist (SQ 29 548), the
      thromboxane A2 (TXA2) synthase inhibitor furegrelate, and the prostacyclin (PGI2)
      synthesis inhibitor tranylcypromine (TCP). In addition, COX-2 protein expression
      was studied by Western blot analysis. Release of prostaglandin E2 (PGE2) and the
      metabolites of PGF2alpha, TXA2, and PGI2, 13,14-dihydro-15-keto PGF2a, TXB2, and
      6-keto-PGF1alpha, respectively, were measured. Treatment with aldosterone did not
      modify blood pressure levels in any strain. However, aldosterone markedly reduced
      (P<0.05) ACh-induced relaxations in segments from both strains in a similar
      extent. Indomethacin, NS-398, SQ 29 548, and TCP enhanced (P<0.05) ACh
      relaxations in both strains treated with aldosterone. Aortic COX-2 protein
      expression was higher in both strains of rats treated with aldosterone. In
      normotensive animals, aldosterone increases the ACh-stimulated aortic production
      of 13,14-dihydro-15-keto PGF2a, PGE2, and 6-keto-PGF1alpha (P<0.05). In SHR, ACh
      only increased the 6-keto-PGF1alpha production (P<0.05). It could be concluded
      that chronic treatment with aldosterone was able to produce endothelial
      dysfunction through COX-2 activation in normotensive and hypertensive conditions.
      PGI2 seems to be the main factor accounting for endothelial dysfunction in
      hypertensive rats, whereas other prostanoids besides PGI2 appear to be involved
      in endothelial dysfunction under normotensive conditions.

PMID- 15956110
TI  - High sodium intake increases blood pressure and alters renal function in
      intrauterine growth-retarded rats.
AB  - A suboptimal fetal environment increases the risk to develop cardiovascular
      disease in the adult. We reported previously that intrauterine stress in response
      to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and
      compromises renal development, leading to an altered renal function in the adult
      offspring. Here we tested the hypothesis that high dietary sodium intake in rats
      with impaired renal development attributable to intrauterine stress, results in
      increased blood pressure, altered renal function, and organ damage. In rats,
      intrauterine stress was induced by bilateral ligation of the uterine arteries at
      day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium
      drinking water (2% sodium chloride). At the age of 16 weeks, rats were
      instrumented for monitoring of blood pressure and renal function. After
      intrauterine stress, litter size and birth weight were reduced, whereas
      hematocrit at birth was increased. Renal blood flow, glomerular filtration rate,
      and the glomerular filtration fraction were increased significantly after
      intrauterine stress. High sodium intake did not change renal function and blood
      pressure in control animals. However, during high sodium intake in intrauterine
      stress offspring, renal blood flow, glomerular filtration rate, and the
      filtration fraction were decreased, and blood pressure was increased. In
      addition, these animals developed severe albuminuria, an important sign of renal
      dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal
      development, results in sodium-dependent hypertension and albuminuria.

PMID- 15956111
TI  - Modest salt reduction lowers blood pressure in isolated systolic hypertension and
      combined hypertension.
AB  - Many randomized trials have shown that a reduction in salt intake lowers blood
      pressure in hypertensive individuals. However, few have looked at the effects
      according to hypertension category. A recent analysis of the third and fourth
      National Health and Nutrition Examination Survey suggests that salt intake may
      not be related to blood pressure in isolated systolic or combined hypertension.
      To look at this further, we reanalyzed the data of our previous salt reduction
      trials. Hypertensive individuals were studied in randomized double-blind
      crossover studies: 1 month of usual salt intake compared with 1 month of reduced
      salt intake. In isolated systolic hypertension (n=24), blood pressure was reduced
      from 166+/-19/86+/-7 to 156+/-20/85+/-7 mm Hg (systolic P<0.001; diastolic
      P=0.459) with a reduction in urinary sodium from 175+/-51 to 87+/-38 mmol per 24
      hour period (10.3 to 5.1 g per day of salt). In combined hypertension (n=88),
      blood pressure was reduced from 161+/-16/100+/-9 to 154+/-17/96+/-9 mm Hg
      (P<0.001) with a reduction urinary sodium from 176+/-65 to 98+/-51 mmol per 24
      hour period (10.4 to 5.8 g per day of salt). These results demonstrate that salt
      reduction has a significant effect on blood pressure in isolated systolic and
      combined hypertension. The fall in systolic observed in isolated systolic
      hypertension would be predicted to reduce stroke by approximately one third,
      ischemic heart disease by one quarter, and heart failure by one quarter in the
      population between 60 and 80 years of age, in whom isolated systolic hypertension
      is the predominate form of hypertension and carries the highest risk. These
      results provide strong support for universal salt reduction in all hypertensives.

PMID- 15956112
TI  - Salt restriction in the treatment of isolated systolic and combined hypertension:
      is that enough?

PMID- 15956114
TI  - Aldosterone nongenomically worsens ischemia via protein kinase C-dependent
      pathways in hypoperfused canine hearts.
AB  - Rapid nongenomic actions of aldosterone independent of mineralocorticoid
      receptors (MRs) on vascular tone are divergent. Until now, the rapid nongenomic
      actions of aldosterone on vascular tone of coronary artery and cardiac function
      in the in vivo ischemic hearts were not still fully estimated. Furthermore,
      although aldosterone can modulate protein kinase C (PKC) activity, there is no
      clear consensus whether PKC is involved in the nongenomic actions of aldosterone
      on the ischemic hearts. In open chest dogs, the selective infusion of aldosterone
      into the left anterior descending coronary artery (LAD) reduced coronary blood
      flow (CBF) in the nonischemic hearts in a dose-dependent manner. Also, in the
      ischemic state that CBF was decreased to 33% of the baseline, the intracoronary
      administration of aldosterone (0.1 nmol/L) rapidly decreased CBF (37.4+/-3.8 to
      19.3+/-5.2 mL/100 g/min; P<0.05), along with decreases in fractional shortening
      (FS) (8.4+/-0.7 to 5.4+/-0.4%; P<0.05) and lactate extraction rate (LER) (-31.7+/
      2.9 to -41.4+/-3.7%; P<0.05). The decrease in CBF was reproduced by the infusion
      of bovine serum albumin-conjugated aldosterone. Notably, these aldosterone
      induced deteriorations of myocardial contractile and metabolic functions were
      blunted by the co-administration of GF109203X, an inhibitor of PKC, but not
      spironolactone. In addition, aldosterone activated vascular PKC. These results
      indicate that aldosterone nongenomically induces vasoconstriction via PKC
      dependent pathways possibly through membrane receptors, which leads to the
      worsening of the cardiac contractile and metabolic functions in the ischemic
      hearts. Elevation of plasma or cardiac aldosterone levels may be deleterious to
      ischemic heart disease through its nongenomic effects.

PMID- 15956113
TI  - Urine albumin excretion and subclinical cardiovascular disease. The Multi-Ethnic
      Study of Atherosclerosis.
AB  - We examined the association between urine albumin excretion (UAE) and common and
      internal carotid artery intima-media thickness (IMT), end-diastolic left
      ventricular (LV) mass, and coronary artery calcification (CAC) scores using data
      from the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study
      of 6814 adults aged 45 to 85 years without clinical cardiovascular disease (CVD).
      The mean age of the MESA participants was 62.7 years, 47% were male, and 15% had
      diabetes mellitus (DM). Sex-specific spot urine albumin/creatinine ratios were
      used to define 4 UAE categories: normal, high normal, microalbuminuria, and
      macroalbuminuria. CAC scores were log-transformed after adding 1 to all scores.
      Mean values of subclinical CVD measures were computed by level of UAE after
      adjustment for blood pressure, DM, and other covariates. After adjustment for all
      covariates, geometric mean CAC scores were higher among participants with high
      normal UAE (8.8; P=0.07), microalbuminuria (9.9; P=0.002), and macroalbuminuria
      (13.1; P=0.02) compared with normal UAE (7.4), but only microalbuminuria reached
      statistical significance. Mean LV mass (g/m2.7) was significantly higher in
      participants with high normal UAE (37.0; P=0.001), microalbuminuria (38.3; P< or
      =0.0001), and macroalbuminuria (42.3; P< or =0.0001) compared with normal UAE
      (36.0) after adjustment for all covariates. No significant difference in mean
      carotid IMT was found after adjustment for all covariates. Similar results were
      noted in MESA participants with and without DM. In conclusion, higher UAE,
      including levels below microalbuminuria, may reflect the presence of subclinical
      CVD among adults without established CVD.

PMID- 15956115
TI  - C-reactive protein elevation predicts pulse pressure reduction in hypertensive
      subjects.
AB  - Cross-sectional studies have shown a positive association between increased pulse
      pressure (PP) and an increased likelihood of a C-reactive protein (CRP) level >3
      mg/L. In a retrospective subgroup analysis of the hypertensive subjects of the
      multicenter double-blind study, REASON (PREterax in Regression of Arterial
      Stiffness in a ContrOlled Double-BliNd), in which fixed first-line
      antihypertensive combination therapy with an angiotensin converting enzyme (ACE)
      inhibitor, perindopril (2 mg), and a diuretic, indapamide (0.625 mg), proved
      significantly more effective than atenolol in normalizing PP, we sought to
      determine whether perindopril plus indapamide was also more effective than
      atenolol in lowering CRP levels and, if so, whether this effect correlated with a
      preferential reduction in PP. At the final visit (12 months) in the 269 patients
      studied, the decrease in PP was greater, and the proportion of patients with CRP
      >3 mg/L lower (17.9% versus 28. 9%, P=0.03; adjusted odds ratio, 1.02 to 4.08,
      P=0.01), in the perindopril plus indapamide group than in the atenolol group.
      After adjustment for confounders, patients with a baseline CRP >3 mg/L displaying
      the greatest decrease in PP were more likely (P=0.04) to have a CRP < or =3 mg/L
      at 12 months. No such relationship was found with systolic or diastolic blood
      pressure. Perindopril-indapamide combination therapy is more effective than beta
      blockade in lowering elevated CRP in hypertensive subjects. This effect is
      significantly associated with a more effective PP reduction in patients with
      baseline CRP >3 mg/L.

PMID- 15956116
TI  - Rapid effects of aldosterone: relevant in cardiac ischemia?

PMID- 15956117
TI  - Endothelin-1 (1-31) is an intermediate in the production of endothelin-1 after
      big endothelin-1 administration in vivo.
AB  - The precursor of endothelin-1, big endothelin-1, can be hydrolyzed by chymase to
      generate endothelin-1 (1-31) in vitro. In the present study, we explored the
      processes involved in the production of endothelin-1 (1-31) as well as its
      pharmacodynamic characteristics in the rabbit in vivo. Endothelin-1 (1-31) (1
      nmol/kg, injected into the left cardiac ventricle) induced a monophasic increase
      of mean arterial blood pressure similarly to big endothelin-1 (1-38), whereas
      endothelin-1 induces a biphasic response. Phosphoramidon, a dual neutral
      endopeptidase and endothelin-converting enzyme inhibitor, blocked both pressor
      responses to endothelin-1 (1-31) and big endothelin-1 but not those afforded by
      endothelin-1. Thiorphan, a neutral endopeptidase inhibitor, markedly inhibited
      the response to endothelin-1 (1-31) but only weakly reduced that of big
      endothelin-1. In contrast, CGS 35066, an endothelin-converting enzyme inhibitor,
      was significantly more efficient against the pressor response to big endothelin-1
      than to endothelin-1 (1-31). Furthermore, injection of big endothelin-1
      concomitantly with phosphoramidon induced an increase in endothelin-1 (1-31)
      plasma levels. Finally, intracardiac-administered endothelin-1 (1-31) induced an
      increase of endothelin-1 plasma levels, which are markedly reduced by
      phosphoramidon and thiorphan but not by CGS 35066. Our results thus demonstrate
      that endothelin-1 (1-31) is an alternate intermediate in the production of
      endothelin-1 after big endothelin-1 administration in the rabbit in vivo.

PMID- 15956118
TI  - Therapeutic potential of endothelial progenitor cells in cardiovascular diseases.
AB  - Endothelial dysfunction and cell loss are prominent features in cardiovascular
      disease. Endothelial progenitor cells (EPCs) originating from the bone marrow
      play a significant role in neovascularization of ischemic tissues and in re
      endothelialization of injured blood vessels. Several studies have shown the
      therapeutic potential of EPC transplantation in rescue of tissue ischemia and in
      repair of blood vessels and bioengineering of prosthetic grafts. Recent small
      scale trials have provided preliminary evidence of feasibility, safety, and
      efficacy in patients with myocardial and critical limb ischemia. However, several
      studies have shown that age and cardiovascular disease risk factors reduce the
      availability of circulating EPCs (CEPCs) and impair their function to varying
      degrees. In addition, the relative scarcity of CEPCs limits the ability to expand
      these cells in sufficient numbers for some therapeutic applications. Priority
      must be given to the development of strategies to enhance the number and improve
      the function of CEPCs. Furthermore, alternative sources of EPC such as chord
      blood need to be explored. Strategies for improvement of cell adhesion, survival,
      and prevention of cell senescence are also essential to ensure therapeutic
      viability. Genetic engineering of EPCs may be a useful approach to developing
      these cells into efficient therapeutic tools. In the clinical arena there is
      pressing need to standardize the protocols for isolation, culture, and
      therapeutic application of EPC. Large-scale multi-center randomized trials are
      required to evaluate the long-term safety and efficacy of EPC therapy. Despite
      these hurdles, the outlook for EPC-based therapy for cardiovascular disease is
      promising.

PMID- 15956120
TI  - Impaired elastic properties of the ascending aorta in newborns before and early
      after successful coarctation repair: proof of a systemic vascular disease of the
      prestenotic arteries?
AB  - BACKGROUND: Despite successful surgical correction, morbidity of patients with
      coarctation of the aorta is increased. It is well known that these patients have
      impaired elastic properties of the prestenotic arteries. To find out whether
      these abnormalities are primarily present or develop later, we studied 17
      newborns before and early after surgical repair. METHODS AND RESULTS: Aortic wall
      stiffness index and distensibility were calculated using ascending and abdominal
      aortic diameters determined by M-mode echocardiography and noninvasive estimation
      of aortic pulse pressure in the right arm and leg. Seventeen patients with aortic
      coarctation (mean age, 20+/-26 days) were compared with 17 normal neonates (mean
      age, 13+/-7 days) preoperatively and postoperatively (10+/-6 days after surgery).
      Ascending aortic distensibility in patients was significantly reduced
      preoperatively (79+/-58 versus 105+/-36; P=0.03) and postoperatively (65+/-24
      versus 105+/-36; P<0.005). Preoperative and postoperative ascending aortic
      stiffness index was higher in patients (preoperative, 5.2+/-4.4 versus 2.7+/-0.9;
      P=0.04; postoperative, 4.0+/-1.6 versus 2.7+/-0.9; P<0.005). Elastic properties
      of the descending aorta did not differ preoperatively or postoperatively compared
      with those in normal subjects. CONCLUSIONS: Elastic properties of the prestenotic
      aorta of patients with coarctation seem to be impaired primarily, even in
      neonates, and remain unchanged early after successful operation. Surgical
      correction does not resolve inborn pathology of the prestenotic aortic vascular
      bed.

PMID- 15956119
TI  - Rho-kinase mediates hyperglycemia-induced plasminogen activator inhibitor-1
      expression in vascular endothelial cells.
AB  - BACKGROUND: Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are
      associated with myocardial infarction and stroke, especially in patients with
      diabetes. The induction of PAI-1 expression by hyperglycemia involves oxidative
      stress and protein kinase C (PKC). However, the mechanism by which hyperglycemia
      increases PAI-1 expression is unknown. METHODS AND RESULTS: Compared with
      normoglycemia, exposure of human endothelial cells to hyperglycemia, but not
      mannitol, increased Rho-kinase activity in a time- and concentration-dependent
      manner. This increase was inhibited by a PKC inhibitor, GF109203X, and
      antioxidants N-acetylcysteine (NAC) and reduced form of glutathione (GSH). This
      correlated with inhibition of hyperglycemia-induced PAI-1 expression by
      GF109203X, NAC, and GSH. Hyperglycemia-increased PAI-1 mRNA and protein levels
      were inhibited by Rho-kinase inhibitors hydroxyfasudil and Y27632 and by a
      dominant-negative mutant of Rho-kinase. The mechanism for this inhibition occurs
      at the level of gene transcription because Rho-kinase inhibitors repress
      hyperglycemia-stimulated PAI-1 promoter activity without affecting mRNA
      stability. Hyperglycemia failed to stimulate Rho-kinase activity and PAI-1
      expression in heterozygous ROCK I-knockout murine endothelial cells. CONCLUSIONS:
      Hyperglycemia stimulates Rho-kinase activity via PKC- and oxidative stress
      dependent pathways, leading to increased PAI-1 gene transcription. These results
      suggest that inhibition of ROCK I may be a novel therapeutic target for
      preventing thromboembolic complications of diabetes and cardiovascular disease.

PMID- 15956121
TI  - Effects of exercise and ischemia on mobilization and functional activation of
      blood-derived progenitor cells in patients with ischemic syndromes: results of 3
      randomized studies.
AB  - BACKGROUND: Exercise training (ET) has been shown to improve regional perfusion
      in ischemic syndromes. This might be partially related to a regeneration of
      diseased endothelium by circulating progenitor cells (CPCs) or CPC-derived
      vasculogenesis. The aim of the present study was to determine whether ischemic
      stimuli during ET are required to promote CPC mobilization in patients with
      cardiovascular diseases. METHODS AND RESULTS: Patients with peripheral arterial
      occlusive disease (PAOD) were randomized to 4 weeks of daily ischemic ET or
      control (group A). Successfully revascularized patients with PAOD were randomized
      to 4 weeks of daily nonischemic ET or control (group B). Patients with stable
      coronary artery disease were subjected to 4 weeks of subischemic ET or control
      (group C). At baseline and after 4 weeks, the number of KDR+/CD34+ CPCs was
      determined by fluorescence-activated cell sorting analysis. Levels of vascular
      endothelial growth factor (VEGF) were measured by ELISA. A Matrigel assay was
      used to quantify CPC integration into vascular structures. Expression of the
      homing factor CXCR4 was determined by reverse transcription-polymerase chain
      reaction. In group A only, ischemic ET increased VEGF levels by 310% (P<0.05
      versus control) associated with an increase in CPCs by 440% (P<0.05 versus
      control), increased CXCR4 expression, and enhanced integration of CPCs into
      endothelial networks. In contrast, subischemic ET in groups B and C increased
      CXCR4 expression and CPC integration. CONCLUSIONS: In training programs,
      symptomatic tissue ischemia seems to be a prerequisite for CPC mobilization.
      However, ischemic and subischemic ET programs affect CXCR4 expression of CPCs,
      which might lead to an improved CPC integration into endothelial networks.

PMID- 15956122
TI  - Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of
      weight gain and blood pressure elevation over 5 years.
AB  - BACKGROUND: The genes responsible for obesity are candidate genes for obesity
      related diseases, such as hypertension. Functional polymorphisms in the beta2-
      and beta3-adrenergic receptors have been reported to be associated with
      hypertension and obesity. METHODS AND RESULTS: To longitudinally clarify the
      relevance to alterations in beta-adrenergic receptor polymorphisms related to
      weight gain, blood pressure (BP) elevation, and sympathetic nerve activity as
      measured by plasma norepinephrine level, we studied 160 young, nonobese,
      normotensive men. Changes in body weight, BP, plasma norepinephrine levels, and
      beta2-adrenergic (Arg16Gly, Gln27Glu) and beta3-adrenergic (Trp64Arg) receptor
      polymorphisms were measured periodically over a 5-year period. Weight gain and BP
      elevation were defined as > or =10% increases from entry levels over 5 years in
      body mass index or mean BP. The presence of the Gly16 allele of Arg16Gly was
      associated with a higher frequency of weight gain and BP elevation over the 5
      year period. The subjects carrying the Glu27 allele of Gln27Glu and the Trp64
      allele of Trp64Arg had a higher frequency of BP elevation. Significantly higher
      levels of plasma norepinephrine at entry and at year 5 were observed in the
      subjects with the Gly16 allele of Arg16Gly and the Glu27 allele of Gln27Glu
      compared with those without the Gly16 or the Glu27 alleles. CONCLUSIONS: These
      results demonstrate that the Gly16 allele is related to greater weight gain and
      BP elevation. Additionally, Glu27 and Trp64 alleles are linked to BP elevation.
      The subjects carrying the beta2-polymorphisms linked to weight gain and BP
      elevation also have higher plasma norepinephrine levels that are present at entry
      before weight gain and BP elevation. These findings suggest that beta2-adrenergic
      receptor polymorphisms in association with a heightened sympathetic nerve
      activity could predict the future onset of obesity and hypertension, as shown in
      the 5-year longitudinal study.

PMID- 15956123
TI  - Magnitude of and risk factors for in-hospital and postdischarge stroke in
      patients with acute coronary syndromes: findings from a Global Registry of Acute
      Coronary Events.
AB  - BACKGROUND: Stroke is a recognized complication after acute myocardial
      infarction, but few studies have investigated the incidence and outcome of stroke
      in patients with acute coronary syndrome (ACS). This study examined the incidence
      and outcomes of hemorrhagic and nonhemorrhagic stroke and risk factors associated
      with stroke in patients with ACS. METHODS AND RESULTS: Data were obtained from
      35,233 patients enrolled in the Global Registry of Acute Coronary Events (GRACE)
      with an ACS. In-hospital strokes occurred in 310 patients (0.9%), of which 100
      (32.6%) were fatal. The incidence of in-hospital stroke was significantly higher
      in patients with ST-segment-elevation myocardial infarction than in non-ST
      segment myocardial infarction or unstable angina (1.3%, 0.9%, 0.5%, respectively;
      P<0.001). Overall, 35.5% of in-hospital strokes occurred within 6 days of
      hospitalization. The strongest risk factor for in-hospital nonhemorrhagic stroke
      was in-hospital CABG, followed by in-hospital atrial fibrillation, previous
      stroke, initial enzyme elevation, and advanced age. Prior statin use was a
      protective factor. After controlling for potential confounders, in-hospital
      mortality was significantly higher among patients who experienced an in-hospital
      stroke (adjusted odds ratio, 8.3; 95% CI, 6.0 to 11.4). A total of 269 additional
      strokes (1.1%) occurred within 6 months after discharge from hospital, of which
      56 (20.9%) were fatal. The most important risk factor for postdischarge stroke
      was the occurrence of an in-hospital stroke. CONCLUSIONS: Stroke is an uncommon
      event in patients with ACS but is associated with high mortality. Despite current
      therapy, the incidence of postdischarge stroke is not low. New approaches are
      warranted to reduce the risk of stroke in patients with ACS.

PMID- 15956124
TI  - Trial to evaluate the management of paroxysmal supraventricular tachycardia
      during an electrophysiology study with tecadenoson.
AB  - BACKGROUND: Tecadenoson is a potent selective A1-adenosine receptor agonist with
      a dose-dependent negative dromotropic effect on the AV node. Tecadenoson
      terminates induced paroxysmal supraventricular tachycardia (PSVT) without the
      clinically significant side effects caused by stimulation of other adenosine
      receptors. This trial was designed to determine a safe and effective tecadenoson
      bolus for termination of electrophysiologically induced PSVT. METHODS AND
      RESULTS: Patients with a history of symptomatic PSVT and inducible PSVT at the
      time of a clinically indicated electrophysiology study were randomized into a
      multicenter, double-blind, placebo-controlled trial. Five 2-dose tecadenoson
      bolus regimens were evaluated versus placebo (75/150, 150/300, 300/600, 450/900,
      900 microg/900 microg). The second bolus was administered only if PSVT persisted
      for 1 minute after the first bolus. Each tecadenoson regimen resulted in a
      significant therapeutic conversion rate compared with placebo (range, 50.0% to
      90.3%, analysis of all patients dosed; n=181; P<0.0005). Conversion by the first
      bolus was dose related (range: placebo, 3.3% to 86.7% for 900 microg/900 microg).
      Time to conversion was dose dependent, with a median time of <1 minute for the 3
      highest dose regimens. Postconversion arrhythmias were transient, requiring no
      additional treatment in 4 regimens (including placebo). Transient second- and
      third-degree heart block occurred at higher doses (300/600, 450/900, 900
      microg/900 microg) and was supported with backup pacing when needed. No effect on
      blood pressure was observed. Ten patients with a history of asthma or chronic
      obstructive pulmonary disease tolerated tecadenoson without bronchospasm.
      CONCLUSIONS: We identified an optimal tecadenoson regimen (300 microg/600 microg)
      that effectively and rapidly converted 90% (28 of 31) of PSVT patients to normal
      sinus rhythm with no significant adverse effects.

PMID- 15956125
TI  - Short- and long-term success of substrate-based mapping and ablation of
      ventricular tachycardia in arrhythmogenic right ventricular dysplasia.
AB  - BACKGROUND: Multiple morphologies, hemodynamic instability, or noninducibility
      may limit ventricular tachycardia (VT) ablation in patients with arrhythmogenic
      right ventricular dysplasia (ARVD). Substrate-based mapping and ablation may
      overcome these limitations. We report the results and success of substrate-based
      VT ablation in ARVD. METHODS AND RESULTS: Twenty-two patients with ARVD were
      studied. Traditional mapping for VT was limited because of multiple/changing VT
      morphologies (n=14), nonsustained VT (n=10), or hemodynamic intolerance (n=5).
      Sinus rhythm CARTO mapping was performed to define areas of "scar" (<0.5 mV) and
      "abnormal" myocardium (0.5 to 1.5 mV). Ablation was performed in "abnormal"
      regions, targeting sites with good pace maps compared with the induced VT(s).
      Linear lesions were created in these areas to (1) connect the scar/abnormal
      region to a valve continuity or other scar or (2) encircle the scar/abnormal
      region. Eighteen patients had implanted cardioverter defibrillators, 15 had
      implanted cardioverter defibrillator therapies, and 7 had sustained VT (6 with
      syncope). VTs (3+/-2 per patient) were induced (cycle length, 339+/-94 ms), and
      scar was identified in all patients. Scar areas were related to the tricuspid
      annulus, proximal right ventricular outflow tract, and anterior/inferior-apical
      walls. Lesions connected abnormal regions to the annulus (n=12) or other scars
      (n=4) and/or encircled abnormal regions (n=13). Per patient, a mean of 38+/-22
      radiofrequency lesions was applied. Short-term success was achieved in 18
      patients (82%). VT recurred in 23%, 27%, and 47% of patients after 1, 2, and 3
      years' follow-up, respectively. CONCLUSIONS: Substrate-based ablation of VT in
      ARVD can achieve a good short-term success rate. However, recurrences become
      increasingly common during long-term follow-up.

PMID- 15956126
TI  - Long-term, randomized comparison of balloon angioplasty and surgery for native
      coarctation of the aorta in childhood.
AB  - BACKGROUND: The purpose of this study was to compare the long-term outcomes of
      children randomized to surgery or balloon angioplasty (BA) for native coarctation
      (CoA). A prior randomized, short-term comparison of BA and surgery for native CoA
      in 36 children demonstrated equivalent relief of obstruction. The risk of
      aneurysm formation and possibly restenosis was higher among patients treated with
      BA. METHODS AND RESULTS: Blood pressure, residual aortic obstruction, and
      exercise performance were evaluated. Need for repeat intervention was reviewed.
      Aortic arch anatomy was assessed with magnetic resonance angiography. For
      subjects who were not available to return for evaluation, the most recent
      clinical record was utilized. Among the 36 subjects initially randomized, 21
      returned for evaluation (11 BA, 10 surgery). The average time since initial
      intervention to evaluation for all subjects was 10.6+/-4.7 years for BA subjects
      and 11.3+/-3.7 years for surgical subjects. Resting blood pressure, CoA gradient,
      exercise performance, MRI analysis of the aortic arch, and need for repeat
      interventions were not different for the 2 treatment strategies. There was a
      higher incidence of aneurysm formation (35% versus 0%) and a greater difference
      in blood pressure between the right and left legs with exercise among BA
      subjects. Some aneurysms developed late, first being detected more than 5 years
      after the initial intervention. Only 50% of BA subjects remained free of both
      aneurysm formation and repeat intervention compared with 87.5% of surgical
      subjects (P=0.03). CONCLUSIONS: BA for the treatment of childhood CoA is
      associated with a higher incidence of aneurysm formation and iliofemoral artery
      injury than surgery. These differences should be considered when undertaking
      treatment for native CoA during childhood.

PMID- 15956127
TI  - Doppler estimation of left ventricular filling pressures in patients with mitral
      valve disease.
AB  - BACKGROUND: Conventional Doppler measurements have limitations in the prediction
      of left atrial pressure (LAP) in patients with mitral valve disease (MVD), given
      the confounding effect of valve area, left ventricular (LV) relaxation, and
      stiffness. However, the time interval between the onset of early diastolic mitral
      inflow velocity (E) and annular early diastolic velocity (Ea) by tissue Doppler
      imaging (TDI), T(E-Ea), which is well related to the time constant of LV
      relaxation (tau) in canine and clinical studies, is not subject to these
      variables. We therefore undertook this study to test its usefulness in a patient
      population. METHODS AND RESULTS: Two-dimensional Doppler and TDI echocardiography
      were performed simultaneously with right-heart catheterization in 51 consecutive
      patients (mean+/-SD age, 64+/-11 years) with MVD: 35 with moderately severe to
      severe mitral regurgitation (MR) and 16 with moderate to severe mitral stenosis
      (MS). Among several Doppler measurements, only the mitral E/A ratio,
      isovolumetric relaxation time (IVRT), and pulmonary venous Ar duration had
      significant relations with mean pulmonary capillary wedge pressure (PCWP). The
      ratio of IVRT to T(E-Ea) (for MR, r=-0.92; for MS, r=-0.88; both P<0.001) and the
      ratio of IVRT to tau (for MR, r=-0.74; for MS, r=-0.85; both P<0.001) had the
      best correlations with PCWP. In 54 repeat studies, including those performed
      after MV repair or replacement, these ratios tracked well the changes in PCWP and
      readily identified changes in mean PCWP by > or =5 mm Hg. A similar correlation
      was noted in 13 patients with atrial fibrillation (r=-0.92, P<0.01) and in a
      prospective group of 14 patients with MR (r=-0.93, P<0.001). CONCLUSIONS: The
      ratio of IVRT to T(E-Ea) or to tau can be readily applied for estimating mean
      PCWP in patients with MVD and can track changes in PCWP after valve surgery.

PMID- 15956128
TI  - Thoracic spinal cord stimulation reduces the risk of ischemic ventricular
      arrhythmias in a postinfarction heart failure canine model.
AB  - BACKGROUND: Thoracic spinal cord stimulation (SCS) is a promising therapy in
      treating refractory angina. This study was designed to investigate SCS with
      regard to the risk of arrhythmias during myocardial ischemia and its cardiac
      electrophysiological effects. METHODS AND RESULTS: We studied 22 dogs with healed
      anterior myocardial infarction (MI) and superimposed heart failure (HF) induced
      by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the
      spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial
      ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke
      ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation;
      VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly
      assigned to receive SCS or no SCS before the first or second ischemic episode.
      SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during
      transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626
      to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048),
      increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood
      pressure by 9.8+/-13.6 mm Hg (P=0.02). CONCLUSIONS: Thoracic SCS appears to
      protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced
      sinus rate and systolic blood pressure, changes consistent with the previously
      known antisympathetic effect of SCS, which may have contributed to the
      antiarrhythmic benefits.

PMID- 15956129
TI  - Impact of prosthesis-patient size on functional recovery after aortic valve
      replacement.
AB  - BACKGROUND: Prosthesis-patient size mismatch results when an implanted prosthetic
      aortic valve is of insufficient size for a patient's body surface area. The
      relation between prosthesis-patient size and functional capacity and adverse
      postoperative outcome is inconsistent. Our objectives were to examine the impact
      of valve replacement, continuous prosthesis-patient size, and other factors on
      functional recovery after aortic valve replacement (AVR) with the Duke Activity
      Status Index (DASI). METHODS AND RESULTS: From June 15, 1995, through May 14,
      1998, 1108 patients underwent AVR after completing a DASI survey. Of these, 1014
      completed a postoperative DASI survey at an average of 8.3 months
      postoperatively. Logistic ordinal regression was used to examine the influence of
      demographic variables, comorbidities, baseline DASI scores, indexed valve orifice
      area, standardized orifice size, and postoperative morbid events on postoperative
      DASI. There was overall improvement in postoperative functional recovery
      reflected by median preoperative and postoperative DASI scores of 29 and 46,
      P<0.001, respectively. Neither indexed orifice area, P=0.94, nor standardized
      orifice size, P=0.96, was associated with functional recovery. Female sex,
      increasing age, elevated serum creatinine, increased central venous pressure, and
      red blood cell transfusion were factors associated with poor postoperative
      functional recovery. CONCLUSIONS: A majority of patients report improvement in
      functional quality of life early after AVR. Similar functional recovery was
      demonstrated for patients along the full spectrum of valve sizes indexed to body
      size, even for values considered to represent severe mismatch for patient size.
      Factors other than prosthesis-patient size influence functional quality of life
      early after AVR.

PMID- 15956130
TI  - External beam radiation to prevent restenosis after superficial femoral artery
      balloon angioplasty.
AB  - BACKGROUND: Femoropopliteal percutaneous transluminal angioplasty (PTA) remains
      limited by restenosis. Although vascular brachytherapy may be effective in
      reducing restenosis, external beam radiation would be more practical to
      administer after PTA. METHODS AND RESULTS: After femoropopliteal PTA without
      stent placement, 99 patients were randomly assigned to 0 Gy (placebo; n=24), 7 Gy
      (n=24), 10.5 Gy (n=26), or 14 Gy (n=25) of external beam radiation of the PTA
      site (with a 3-cm margin at both extremities) in 1 session 24 hours after PTA.
      The primary end point was minimum lumen diameter on quantitative angiography 1
      year after PTA. One year after PTA, the mean minimum lumen diameter was 1.92,
      1.64, 1.92, and 2.91 mm, respectively, for the 0-, 7-, 10.5-, and 14-Gy groups
      (P=0.0072 for 0 versus 14 Gy). Mean luminal loss was 1.14, 1.27, 1.08, and 0.14
      mm, respectively, for the 4 groups (P=0.0072 for 0 versus 14 Gy). Restenosis >50%
      was present in 50%, 65%, 48%, and 25% of patients, respectively, for the 0-, 7-,
      10.5-, and 14-Gy groups (P=0.072). At 18 months, repeated revascularizations were
      required in 25% of patients in the 0-Gy group versus 12% of patients in the 14-Gy
      group (P=0.24). CONCLUSIONS: A single session of external beam radiation of 14 Gy
      of the femoropopliteal angioplasty site significantly reduces restenosis at 1
      year.

PMID- 15956131
TI  - Outcome of 622 adults with asymptomatic, hemodynamically significant aortic
      stenosis during prolonged follow-up.
AB  - BACKGROUND: This study assessed the long-term outcome of a large, asymptomatic
      population with hemodynamically significant aortic stenosis (AS). METHODS AND
      RESULTS: We identified 622 patients with isolated, asymptomatic AS and peak
      systolic velocity > or =4 m/s by Doppler echocardiography who did not undergo
      surgery at the initial evaluation and obtained follow-up (5.4+/-4.0 years) in
      all. Mean age (+/-SD) was 72+/-11 years; there were 384 (62%) men. The
      probability of remaining free of cardiac symptoms while unoperated was 82%, 67%,
      and 33% at 1, 2, and 5 years, respectively. Aortic valve area and left
      ventricular hypertrophy predicted symptom development. During follow-up, 352
      (57%) patients were referred for aortic valve surgery and 265 (43%) patients
      died, including cardiac death in 117 (19%). The 1-, 2-, and 5-year probabilities
      of remaining free of surgery or cardiac death were 80%, 63%, and 25%,
      respectively. Multivariate predictors of all-cause mortality were age (hazard
      ratio [HR], 1.05; P<0.0001), chronic renal failure (HR, 2.41; P=0.004),
      inactivity (HR, 2.00; P=0.001), and aortic valve velocity (HR, 1.46; P=0.03).
      Sudden death without preceding symptoms occurred in 11 (4.1%) of 270 unoperated
      patients. Patients with peak velocity > or =4.5 m/s had a higher likelihood of
      developing symptoms (relative risk, 1.34) or having surgery or cardiac death
      (relative risk, 1.48). CONCLUSIONS: Most patients with asymptomatic,
      hemodynamically significant AS will develop symptoms within 5 years. Sudden death
      occurs in approximately 1%/y. Age, chronic renal failure, inactivity, and aortic
      valve velocity are independently predictive of all-cause mortality.

PMID- 15956132
TI  - Hypothermia improves defibrillation success and resuscitation outcomes from
      ventricular fibrillation.
AB  - BACKGROUND: Induced hypothermia is recommended to improve neurological outcomes
      in unconscious survivors of out-of-hospital ventricular fibrillation (VF) cardiac
      arrest. Patients resuscitated from a VF arrest are at risk of refibrillation, but
      there are few data on the effects of already existing hypothermia on
      defibrillation and resuscitation. METHODS AND RESULTS: Thirty-two swine (mean+/
      SE weight, 23.0+/-0.6 kg) were divided into 4 groups: normothermia (n=8), mild
      hypothermia (35 degrees C) (n=8), moderate hypothermia (33 degrees C) (n=8), and
      severe hypothermia (30 degrees C) (n=8). Hypothermia was induced by surrounding
      the animal with ice, and VF was electrically induced. After 8 minutes of
      unsupported VF (no CPR), the swine were defibrillated (biphasic waveform) with
      successive shocks as needed and underwent CPR until resumption of spontaneous
      circulation or no response (> or =10 minutes). First-shock defibrillation success
      was higher in the moderate hypothermia group (6 of 8 hypothermia versus 1 of 8
      normothermia; P=0.04). The number of shocks needed for late defibrillation (> or
      =1 minute after initial shock) was less in all 3 hypothermia groups compared with
      normothermia (all P<0.05). None of the 8 animals in the normothermia group
      achieved resumption of spontaneous circulation compared with 3 of 8 mild
      hypothermia (P=NS), 7 of 8 moderate hypothermia (P=0.001), and 5 of 8 severe
      hypothermia (P=0.03) animals. Coronary perfusion pressure during CPR was not
      different between the groups. CONCLUSIONS: When VF was induced in the setting of
      moderate or severe hypothermia, resuscitative measures were facilitated with
      significantly improved defibrillation success and resuscitation outcome. The
      beneficial effect of hypothermia was not due to alteration of coronary perfusion
      pressure, which suggests that changes in the mechanical, metabolic, or
      electrophysiological properties of the myocardium may be responsible.

PMID- 15956133
TI  - Calcium concentration of individual coronary calcified plaques as measured by
      multidetector row computed tomography.
AB  - BACKGROUND: Characteristics of individual calcified plaques, especially calcium
      concentration (CC), may provide incremental value to global calcium scores in the
      assessment of plaque burden and risk of coronary events and evaluation of
      therapeutic intervention. In this study, therefore, we assessed the
      characteristics of individual calcified plaques and their relationship to other
      parameters derived from CT analysis of coronary calcium in a community-based
      cross-sectional cohort. METHODS AND RESULTS: Coronary artery calcium (CAC) was
      analyzed in 612 participants of the Framingham Heart Study (third-generation and
      offspring cohorts) using prospectively ECG-triggered multidetector CT. We
      determined the CC, Agatston score, calcified volume, and mineral mass of
      individual calcified plaques in each subject. Heterogeneity of CC was defined as
      the standard deviation of CC of all individual calcified plaques in a subject.
      CAC was detected in 274 of 605 subjects. After excluding 57 subjects (21%)
      because of motion artifacts, we identified a total of 956 calcified coronary
      plaques in 217 subjects (74 women, 143 men; mean age, 57.1+/-10.8 years) with
      detectable CAC and no image artifacts. CC of individual calcified plaques was
      independent of subject age (P=0.76) and sex (197.8+/-74.8 versus 183.6+/-52.8
      mg/cm3 for men versus women; P=0.21). Among a subgroup of 125 subjects with
      multiple (> or =3) individual calcified plaques, CC was heterogeneous within
      individual subjects (mean SD of CC, 43.6+/-23.1 mg/cm3). The degree of
      heterogeneity of CC in these subjects was independent of age (P=0.60), sex
      (P=0.99), and number of plaques (P=0.06). CONCLUSIONS: The CC of individual
      calcified plaques is independent of age and sex but heterogeneous within a
      subject, which may reflect that the pathological process of calcified plaque
      formation and progression is the same in men and women regardless of age. CC may
      have incremental value to global calcium scores in the assessment of plaque
      burden and risk of coronary events and the evaluation of therapeutic
      intervention. Further studies are warranted to confirm that individual plaque
      analysis is preferable to global CAC scores to evaluate progression of
      atherosclerosis and to assess whether individual plaque analysis may be
      complementary to global CAC measures to assess coronary event risk.

PMID- 15956134
TI  - Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at
      alphavbeta3 integrin after murine hindlimb ischemia.
AB  - BACKGROUND: Noninvasive imaging strategies play a critical role in assessment of
      the efficacy of angiogenesis therapies. The alpha(v)beta3 integrin is activated
      in angiogenic vessels and represents a potential target for noninvasive imaging
      of angiogenesis. METHODS AND RESULTS: We evaluated a 99mTc-labeled peptide
      (NC100692) targeted at alpha(v)beta3 integrin for imaging in an established
      murine model of angiogenesis induced by hindlimb ischemia. Control mice (n=9) or
      mice with surgical right femoral artery occlusion (n=29) were injected with
      NC100692 (1.5+/-0.2 mCi IV) at different times after femoral occlusion (1, 3, 7,
      and 14 days) for in vivo pinhole planar gamma camera imaging. Tissue from
      hindlimb proximal and distal to occlusion was excised for gamma well counting and
      for immunostaining. On in vivo pinhole images, increased focal NC100692 activity
      was seen distal to the occlusion at days 3 and 7. This increase in relative
      NC100692 activity was confirmed by gamma well counting. Lectin staining confirmed
      increased angiogenesis in the ischemic hindlimb at these time points. A
      fluorescent analogue of NC100692 was used to confirm specificity and localization
      of the targeted tracer in cultured endothelial cells. In addition, endothelial
      cell specificity was confirmed on tissue sections with the use of dual
      immunofluorescent staining of endothelium and the fluorescent analogue targeted
      at the alpha(v)beta3 integrin. CONCLUSIONS: A 99mTc-labeled peptide (NC100692)
      targeted at alpha(v)beta3 integrin selectively localized to endothelial cells in
      regions of increased angiogenesis and could be used for noninvasive serial "hot
      spot" imaging of angiogenesis. This targeted radiotracer imaging approach is a
      major advance in tracking therapeutic myocardial angiogenesis and has an
      important clinical potential.

PMID- 15956135
TI  - Assessment of endogenous and therapeutic arteriogenesis by contrast ultrasound
      molecular imaging of integrin expression.
AB  - BACKGROUND: We hypothesized that molecular imaging with contrast-enhanced
      ultrasound (CEU) and microbubbles targeted to endothelial integrins could be used
      to noninvasively assess early angiogenic responses to ischemia and growth factor
      therapy. METHODS AND RESULTS: Hindlimb ischemia was produced in 48 rats by
      ligation of an iliac artery. Half of the animals received intramuscular sustained
      release fibroblast growth factor-2 (FGF-2). Immediately after ligation and at
      subsequent intervals from 4 to 28 days, blood flow and oxygen tension in the
      proximal adductor muscles were measured by CEU perfusion imaging and phosphor
      quenching, respectively. Targeted CEU imaging of alpha(v)- and alpha5beta1
      integrin expression was performed with microbubbles bearing the disintegrin
      echistatin. Iliac artery ligation produced a 65% to 70% reduction in blood flow
      and oxygen tension. In untreated ischemic muscle, muscle flow and oxygen tension
      partially recovered by days 14 to 28. In these animals, signal from integrin
      targeted microbubbles was intense and peaked before flow increase (days 4 to 7).
      In comparison to untreated animals, FGF-2-treated muscle had a greater rate and
      extent of blood flow recovery and greater signal intensity from integrin-targeted
      microbubbles, which peaked before maximal recovery of flow. On immunohistology,
      arteriolar but not capillary density increased in the ischemic limb after
      ligation, the rate and degree of which were greater in FGF-2-treated rats.
      Immunofluorescence demonstrated intense staining for alpha(v) in arterioles, the
      temporal course of which correlated with targeted imaging. CONCLUSIONS: Targeted
      CEU can be used to assess endogenous and therapeutic arteriogenesis before
      recovery of tissue perfusion. These results suggest that molecular imaging of
      integrin expression may be useful for evaluating proangiogenic therapies.

PMID- 15956136
TI  - Local expression of platelet-activating factor-acetylhydrolase reduces
      accumulation of oxidized lipoproteins and inhibits inflammation, shear stress
      induced thrombosis, and neointima formation in balloon-injured carotid arteries
      in nonhyperlipidemic rabbits.
AB  - BACKGROUND: Platelet-activating factor (PAF) and PAF-like phospholipids are
      inactivated by PAF-acetylhydrolase (PAF-AH). Using nonhyperlipidemic animals, we
      tested whether local expression of PAF-AH into injured arteries might induce
      antithrombotic and antiinflammatory effects.Method and Results- Balloon-injured
      rabbit carotid arteries were infected at the time of injury with an adenovirus
      expressing either human plasma PAF-AH (AdPAF-AH) or bacterial beta-galactosidase
      (AdLacZ) or infused with saline. Seven days later, shear stress-induced
      thrombosis was observed in all AdLacZ-infected and saline-infused arteries
      (controls) but eliminated in AdPAF-AH-treated contralateral arteries, even in the
      presence of epinephrine or an inhibitor of NO production. Injury-induced
      expression of tissue factor was also significantly suppressed. In AdPAF-AH
      treated arteries compared with controls, the expressions of intercellular
      adhesion molecule-1 and vascular cell adhesion molecule-1 and macrophage
      infiltration were decreased by 66%, 66%, and 71%, respectively (P<0.01), and
      intimal area and intima/media ratio were decreased on day 21 by 43% and 52%,
      respectively (P<0.05). Within 1 week after injury, oxidized lipoproteins (OxLDL)
      had readily accumulated in the arterial wall. However, this was markedly reduced
      in the AdPAF-AH-treated arteries. No differences in the titers of autoantibodies
      to OxLDL or total cholesterol in blood were found between controls and AdPAF-AH
      treated rabbits. CONCLUSIONS: Our results show for the first time that OxLDL
      accumulates in arteries in nonhyperlipidemic animals within 1 week after injury
      and that local expression of PAF-AH reduces this accumulation and exerts
      antiinflammatory, antithrombotic, and antiproliferative effects without changing
      the plasma levels of PAF-AH activity or titers of autoantibodies to OxLDL.

PMID- 15956137
TI  - Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial
      hypertension: twelve-month clinical trial of a single-drug, open-label, pilot
      study.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive and fatal
      disease. Sildenafil is a type 5 phosphodiesterase inhibitor and pulmonary
      vasodilator. Therefore, we hypothesized that sildenafil would improve distance
      walked in 6 minutes and hemodynamics in children with PAH. METHODS AND RESULTS:
      After baseline assessment of hemodynamics by cardiac catheterization and distance
      walked in 6 minutes, we administered oral sildenafil at 0.25 to 1 mg/kg 4 times
      daily to 14 children (median age, 9.8 years; range, 5.3 to 18). Diagnoses were
      primary (n=4) and secondary (n=10) PAH. We repeated the 6-minute walk test at 6
      weeks and at 3, 6, and 12 months (n=14) and cardiac catheterization (n=9) after a
      median follow-up of 10.8 months (range, 6 to 15.3). During sildenafil therapy,
      the mean distance walked in 6 minutes increased from 278+/-114 to 443+/-107 m
      over 6 months (P=0.02), and at 12 months, the distance walked was 432+/-156 m
      (P=0.005). A plateau was reached between 6 and 12 months (P=0.48). Mean pulmonary
      artery pressure decreased from a median of 60 mm Hg (range, 50 to 105) to 50 mm
      Hg (range, 38 to 84) mm Hg (P=0.014). Median pulmonary vascular resistance
      decreased from 15 Wood units m2 (range, 9 to 42) to 12 Wood Units m2 (range, 5 to
      29) (P=0.024). CONCLUSIONS: Oral sildenafil has the potential to improve
      hemodynamics and exercise capacity for up to 12 months in children with PAH.
      Confirmation of these results in a randomized, controlled trial is essential.

PMID- 15956139
TI  - Cardiology patient page. How to respond to an implantable cardioverter
      defibrillator shock.

PMID- 15956138
TI  - Calcified rheumatic valve neoangiogenesis is associated with vascular endothelial
      growth factor expression and osteoblast-like bone formation.
AB  - BACKGROUND: Rheumatic heart disease is the most common cause of valvular disease
      in developing countries. Despite the high prevalence of this disease, the
      cellular mechanisms are not well known. We hypothesized that rheumatic valve
      calcification is associated with an osteoblast bone formation and
      neoangiogenesis. METHODS AND RESULTS: To test this hypothesis, we examined human
      rheumatic valves replaced at surgery (n=23), normal human valves (n=20) removed
      at cardiac transplantation, and degenerative mitral valve leaflets removed during
      surgical valve repair (n=15). Microcomputed tomography was used to assess
      mineralization fronts to reconstruct the extents of mineralization.
      Immunohistochemistry was used to localize osteopontin protein, alpha-actin,
      osteocalcin, vascular endothelial growth factor, von Willebrand factor, and CD68
      (human macrophage). Microcomputed tomography demonstrated complex calcification
      developing within the heavily calcified rheumatic valves, not in the degenerative
      mitral valves and control valves. Immunohistochemistry localized osteopontin and
      osteocalcin to areas of smooth muscle cells within microvessels and proliferating
      myofibroblasts. Vascular endothelial growth factor was present in areas of
      inflammation and colocalized with the CD68 stain primarily in the calcified
      rheumatic valves. Alizarin red, osteopontin, and osteocalcin protein expression
      was upregulated in the calcified rheumatic valves and was present at low levels
      in the degenerative mitral valves. CONCLUSIONS: These findings support the
      concept that rheumatic valve calcification is not a random passive process but a
      regulated, inflammatory cellular process associated with the expression of
      osteoblast markers and neoangiogenesis.

PMID- 15956140
TI  - Images in cardiovascular medicine. Reversible right ventricular hypertrophy due
      to cardiac sarcoidosis.

PMID- 15956141
TI  - Images in cardiovascular medicine. Three-dimensional imaging in rupture of
      papillary muscle after acute myocardial infarction.

PMID- 15956142
TI  - Images in cardiovascular medicine. Angiosarcoma of the pericardium: a fatal
      disease.

PMID- 15956143
TI  - Letter regarding article by Roguin et al, "Modern pacemaker and implantable
      cardioverter/defibrillator systems can be magnetic resonance imaging safe: in
      vitro and in vivo assessment of safety and function at 1.5 t".

PMID- 15956144
TI  - Letter regarding article by Armstrong et al, "Lessons learned from a clinical
      trial".

PMID- 15956146
TI  - Persistent social patterning of cardiovascular risk: rethinking the familiar.

PMID- 15956145
TI  - Infective endocarditis: diagnosis, antimicrobial therapy, and management of
      complications: a statement for healthcare professionals from the Committee on
      Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular
      Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and
      Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by
      the Infectious Diseases Society of America.
AB  - BACKGROUND: Despite advances in medical, surgical, and critical care
      interventions, infective endocarditis remains a disease that is associated with
      considerable morbidity and mortality. The continuing evolution of antimicrobial
      resistance among common pathogens that cause infective endocarditis creates
      additional therapeutic issues for physicians to manage in this potentially life
      threatening illness. METHODS AND RESULTS: This work represents the third
      iteration of an infective endocarditis "treatment" document developed by the
      American Heart Association under the auspices of the Committee on Rheumatic
      Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of
      the Young. It updates recommendations for diagnosis, treatment, and management of
      complications of infective endocarditis. A multidisciplinary committee of experts
      drafted this document to assist physicians in the evolving care of patients with
      infective endocarditis in the new millennium. This extensive document is
      accompanied by an executive summary that covers the key points of the diagnosis,
      antimicrobial therapy, and management of infective endocarditis. For the first
      time, an evidence-based scoring system that is used by the American College of
      Cardiology and the American Heart Association was applied to treatment
      recommendations. Tables also have been included that provide input on the use of
      echocardiography during diagnosis and treatment of infective endocarditis,
      evaluation and treatment of culture-negative endocarditis, and short-term and
      long-term management of patients during and after completion of antimicrobial
      treatment. To assist physicians who care for children, pediatric dosing was added
      to each treatment regimen. CONCLUSIONS: The recommendations outlined in this
      update should assist physicians in all aspects of patient care in the diagnosis,
      medical and surgical treatment, and follow-up of infective endocarditis, as well
      as management of associated complications. Clinical variability and complexity in
      infective endocarditis, however, dictate that these guidelines be used to support
      and not supplant physician-directed decisions in individual patient management.

PMID- 15956147
TI  - Tracking social and biological experiences: the social etiology of cardiovascular
      disease.

PMID- 15956148
TI  - Is rate control or rhythm control preferable in patients with atrial
      fibrillation? Rate control is preferable to rhythm control in the majority of
      patients with atrial fibrillation.

PMID- 15956149
TI  - Is rate control or rhythm control preferable in patients with atrial
      fibrillation? An argument for maintenance of sinus rhythm in patients with atrial
      fibrillation.

PMID- 15956152
TI  - Report of the National Heart, Lung, and Blood Institute working group on outcomes
      research in cardiovascular disease.
AB  - The National Heart, Lung, and Blood Institute convened a working group on
      outcomes research in cardiovascular disease (CVD). The working group sought to
      provide guidance on research priorities in outcomes research related to CVD. For
      the purposes of this document, "outcomes research" is defined as investigative
      endeavors that generate knowledge to improve clinical decision making and
      healthcare delivery to optimize patient outcomes. The working group identified
      the following priority areas: (1) national surveillance projects for high
      prevalence CV conditions; (2) patient-centered care; (3) translation of the best
      science into clinical practice; and (4) studies that place the cost of
      interventions in the context of their real-world effectiveness. Within each of
      these topics, the working group described examples of initiatives that could
      serve the Institute and the public. In addition, the group identified the
      following areas that are important to the field: (1) promotion of the use of
      existing data; (2) facilitation of collaborations with other federal agencies;
      (3) investigations into the basic science of outcomes research, with an emphasis
      on methodological advances; (4) strengthening of appropriate study sections with
      individuals who have expertise in outcomes research; and (5) expansion of
      opportunities to train new outcomes research investigators. The working group
      concluded that a dedicated investment in CV outcomes research could directly
      improve the care delivered in the United States.

PMID- 15956154
TI  - Fatal encephalitis due to rabies virus transmitted by organ transplantation.

PMID- 15956155
TI  - Glatiramer acetate therapy: the plot thickens.

PMID- 15956156
TI  - Hematopoietic stem cell transplantation for multiple sclerosis.

PMID- 15956157
TI  - Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple
      sclerosis: a consensus statement.
AB  - New criteria for the diagnosis of multiple sclerosis (MS) were published as the
      result of an internationally formed committee. To increase the specificity of
      diagnosis and to minimize the number of false diagnoses, the committee
      recommended the use of both clinical and paraclinical criteria, the latter
      involving information obtained from magnetic resonance imaging, evoked
      potentials, and cerebrospinal fluid (CSF) analysis. Although rigorous magnetic
      resonance imaging requirements were provided, the "new criteria paper" fell short
      in terms of guidelines as to how the CSF analysis should be performed and simply
      equated the IgG index with isoelectric focusing, without any justification. The
      spectrum of parameters analyzed and methods for CSF analysis differ worldwide and
      often yield variable results in terms of sensitivity, specificity, accuracy, and
      reliability, with no decided "optimal" CSF test for the diagnosis of MS. To
      address this question specifically, an international panel of experts in MS and
      CSF diagnostic techniques was convened and the result was this article,
      representing a consensus of all the participants. These recommendations for
      establishing a standard for the evaluation of CSF in patients suspected of having
      MS should greatly complement the new criteria in ensuring that a correct
      diagnosis of MS is being made.

PMID- 15956158
TI  - Rabies encephalomyelitis: clinical, neuroradiological, and pathological findings
      in 4 transplant recipients.
AB  - BACKGROUND: Three patients received solid organ transplants from a common donor
      and were subsequently discharged from the hospital following an uneventful
      hospital course. Within 30 days, all 3 organ recipients returned to the hospital
      with varying symptoms that progressed to rapid neurological deterioration, coma,
      and death. OBJECTIVE: To describe the clinical, neuroradiological, and
      pathological findings of rabies virus infection in organ transplant recipients
      infected from a common donor. DESIGN: Case series involving a common donor and 3
      organ recipients ascertained through review of clinical course and autopsy
      findings. A fourth case was determined by review of pending autopsy cases in
      which death occurred within the same time interval. Portions of postmortem
      central nervous system and organ tissues were frozen and formalin-fixed. Fluids
      and tissues were also collected for cultures, serology, and molecular studies.
      Postmortem fluids and tissues and antemortem fluids and tissues from all 4
      transplant recipients and serum and banked lymphocyte or spleen cells from the
      donors were sent to the Centers for Disease Control and Prevention for further
      evaluation. SETTING: Transplant unit of an urban teaching hospital. RESULTS:
      Antemortem cerebrospinal fluid analysis for 3 of the 4 recipients was consistent
      with a viral etiology. Neuroimaging and electroencephalogram studies were
      suggestive of an infectious encephalitis or a toxic encephalopathy. Initial
      laboratory testing did not demonstrate an infectious etiology. Postmortem
      histologic analysis, immunohistochemistry, electron microscopy, and direct
      fluorescence antibody testing revealed rabies virus infection. Serological
      testing done postmortem confirmed rabies virus infection in the common donor.
      CONCLUSIONS: These cases demonstrate a risk for transmitting rabies virus
      infection through solid organ and tissue transplantation, and this diagnosis
      should be considered in any rapidly progressing neurological disease.

PMID- 15956159
TI  - Bystander modulation of chemokine receptor expression on peripheral blood T
      lymphocytes mediated by glatiramer therapy.
AB  - BACKGROUND: Glatiramer acetate therapy is thought to be effective for multiple
      sclerosis (MS) by promoting T(H)2 cytokine deviation, possibly in the brain, but
      the exact mechanism and site of action are incompletely understood. Determining
      the site of action and effect of glatiramer on cell trafficking is of major
      importance in designing rational combination therapy clinical trials. OBJECTIVE:
      To determine whether glatiramer therapy will also act in the peripheral blood
      through bystander modulation of chemokine receptor (CKR) expression and cytokine
      production on T lymphocytes. DESIGN: Before-and-after trial. SETTING: A
      university MS specialty center. PATIENTS: Ten patients with relapsing-remitting
      MS. INTERVENTIONS: Treatment with glatiramer for 12 months and serial phlebotomy.
      MAIN OUTCOME MEASURES: Cytokine production, CKR expression, and cell migration.
      RESULTS: The glatiramer-reactive T cells were T(H)2 cytokine biased, consistent
      with previous studies. We found a significant reduction in the expression of the
      T(H)1 inflammation associated with the CKRs CXCR3, CXCR6, and CCR5 on glatiramer-
      and myelin-reactive T cells generated from patients with MS receiving glatiramer
      therapy vs baseline. Conversely, expression of the lymph node-homing CKR, CCR7,
      was markedly enhanced on the glatiramer-reactive T cells derived from patients
      with MS undergoing glatiramer therapy. There was a reduction in the percentage of
      CD4+ glatiramer-reactive T cells and an increase in the number of CD8+ glatiramer
      reactive T cells. CONCLUSIONS: Glatiramer may suppress autoreactive CD4+ effector
      memory T cells and enhance CD8+ regulatory responses, and bystander modulation of
      CKRs may occur in the periphery.

PMID- 15956160
TI  - Axonal injury and overall tissue loss are not related in primary progressive
      multiple sclerosis.
AB  - BACKGROUND: There is an increasing body of evidence that magnetic resonance
      imaging-occult tissue damage is an important component of primary progressive
      multiple sclerosis (PPMS) pathology. Proton magnetic resonance spectroscopy (1H
      MRS) can be used to measure in vivo whole-brain N-acetylaspartate (WBNAA)
      concentrations, the decrease of whose levels is considered a marker of neuronal
      axonal injury. OBJECTIVES: To study WBNAA 1H-MRS as a tool to provide information
      about irreversible brain damage in PPMS and to investigate the relationship
      between WBNAA and other magnetic resonance imaging measures of MS disease burden,
      including brain atrophy. METHODS: The following magnetic resonance pulse
      sequences of the brain were obtained from 32 patients with PPMS and 16 age
      matched healthy subjects: (1) dual-echo turbo spin-echo; (2) T1-weighted spin
      echo; and (3) 1H-MRS to measure WBNAA concentration. Brain total lesion volumes
      were measured. Normalized brain volumes were calculated using a fully automated
      technique. Absolute WBNAA amounts were calculated using a phantom replacement
      method and were then corrected for individual subjects' brain size. RESULTS:
      Levels of WBNAA concentrations and normalized brain volumes were significantly
      lower in patients with PPMS (mean values, 10.2 mm and 1500.0 mL, respectively)
      than in healthy controls (mean values, 12.9 mm and 1585.2 mL). Both WBNAA
      concentrations and normalized brain volumes were included as independent factors
      in the final model of a multivariable analysis predicting the subjects'
      condition. No significant correlations were found between WBNAA values and
      normalized brain volumes, WBNAA and T2-weighted or T1-weighted lesion volumes.
      CONCLUSIONS: Axonal-neuronal damage in the brain of patients with PPMS seems to
      occur, at least partially, independently of the burden of magnetic resonance
      imaging-visible lesions. Whole-brain N-acetylaspartate values and normalized
      brain volumes were unrelated in this cohort, thereby suggesting that 1H-MRS and
      atrophy assessment may provide in vivo complementary information about the actual
      extent of brain damage in PPMS.

PMID- 15956161
TI  - Intermittent vs continuous levodopa administration in patients with advanced
      Parkinson disease: a clinical and pharmacokinetic study.
AB  - BACKGROUND: Levodopa-related motor complications can be an important source of
      disability for patients with advanced Parkinson disease. Current evidence
      suggests that these motor complications are related to the relatively short half
      life of levodopa and its potential to induce pulsatile stimulation of striatal
      dopamine receptors. Motor complications can be diminished with a continuous
      infusion of levodopa. OBJECTIVE: To investigate the specific pharmacokinetic
      changes associated with the benefits of levodopa infusion. DESIGN: We performed
      an open-label study in 6 patients with Parkinson disease who experienced severe
      motor complications while receiving standard oral formulations of
      levodopa/carbidopa. Patients were subsequently treated for 6 months with
      continuous daytime intraintestinal infusions of levodopa methyl ester. Levodopa
      pharmacokinetic studies were performed at baseline and 6 months in 3 of these
      patients. RESULTS: Compared with treatment with intermittent doses of a standard
      oral formulation of levodopa, continuous infusion provided significant
      improvement in both "off periods" and dyskinesia. Results of plasma
      pharmacokinetic studies demonstrated that compared with oral administration,
      continuous levodopa infusion was associated with a significant increase in the
      levodopa area under the curve and avoided the low plasma trough levels seen with
      oral drug administration. CONCLUSIONS: This study confirms that a continuous
      levodopa infusion is associated with reduced motor complications compared with
      the standard oral formulation of the drug in patients with advanced PD.
      Pharmacokinetic studies demonstrate that reduced motor complications are
      associated with avoiding low plasma levodopa trough levels and are not adversely
      affected by relatively high plasma levodopa concentrations. We propose that if
      levodopa/carbidopa could be administered orally in a manner that mirrors the
      pharmacokinetic pattern of the infusion, it might lead to a similar reduction in
      motor complications.

PMID- 15956162
TI  - Expression profiling of substantia nigra in Parkinson disease, progressive
      supranuclear palsy, and frontotemporal dementia with parkinsonism.
AB  - BACKGROUND: Parkinson disease (PD) is characterized by loss of dopaminergic
      neurons in the substantia nigra. Genes contributing to rare mendelian forms of PD
      have been identified, but the genes involved in the more common idiopathic PD are
      not well understood. OBJECTIVES: To identify genes important to PD pathogenesis
      using microarrays and to investigate their potential to aid in diagnosing
      parkinsonism. DESIGN: Microarray expression analysis of postmortem substantia
      nigra tissue. PATIENTS: Substantia nigra samples from 14 unrelated individuals
      were analyzed, including 6 with PD, 2 with progressive supranuclear palsy, 1 with
      frontotemporal dementia with parkinsonism, and 5 control subjects. MAIN OUTCOME
      MEASURES: Identification of genes significantly differentially expressed (P<.05)
      using Affymetrix U133A microarrays. RESULTS: There were 142 genes that were
      significantly differentially expressed between PD cases and controls and 96 genes
      that were significantly differentially expressed between the combined progressive
      supranuclear palsy and frontotemporal dementia with parkinsonism cases and
      controls. The 12 genes common to all 3 disorders may be related to secondary
      effects. Hierarchical cluster analysis after exclusion of these 12 genes
      differentiated 4 of the 6 PD cases from progressive supranuclear palsy and
      frontotemporal dementia with parkinsonism. CONCLUSIONS: Four main molecular
      pathways are altered in PD substantia nigra: chaperones, ubiquitination, vesicle
      trafficking, and nuclear-encoded mitochondrial genes. These results correlate
      well with expression analyses performed in several PD animal models. Expression
      analyses have promising potential to aid in postmortem diagnostic evaluation of
      parkinsonism.

PMID- 15956163
TI  - Frontotemporal lobar degeneration: demographic characteristics of 353 patients.
AB  - BACKGROUND: Until recently, frontotemporal lobar degeneration (FTLD) was
      considered a rare neurodegenerative disorder that was difficult to diagnose. The
      publication of consensus criteria for FTLD, however, prompted systematic studies.
      The criteria categorize FTLD into 3 subgroups: frontotemporal dementia, semantic
      dementia, and progressive nonfluent aphasia. OBJECTIVE: To compare demographic
      characteristics of patients in the 3 FTLD subgroups. DESIGN: We compared
      diagnostic breakdown, age at onset, sex, Mini-Mental State Examination score at
      first visit, education, and neuropathological diagnoses in a large sample of FTLD
      patients from 3 different university dementia clinics, including 2 neurologic
      clinics in the United States and 1 psychiatric clinic in Germany. RESULTS: The
      frontotemporal dementia subgroup represented approximately half of all FTLD
      diagnoses. Patients diagnosed as having frontotemporal dementia (mean age, 57.5
      years) and semantic dementia (mean age, 59.3 years) had an earlier age at onset
      than patients diagnosed as having progressive nonfluent aphasia (mean age, 63.0
      years). There were significantly more men diagnosed as having frontotemporal
      dementia (63.5%) and semantic dementia (66.7%) when compared with progressive
      nonfluent aphasia (39.1%) (P = .005 for frontotemporal dementia vs progressive
      nonfluent aphasia and P = .002 for semantic dementia vs progressive nonfluent
      aphasia). Generally, the demographic features and diagnostic categories of the
      patient populations across the 3 sites were comparable. There were 68 deaths and
      37 autopsies. Frontotemporal lobar degeneration with ubiquitin-positive tau
      negative inclusions (48.5%), dementia lacking distinctive histopathological
      features (18.2%), and Pick disease (15.2%) were the most common neuropathological
      diagnoses. CONCLUSIONS: These findings show that cohorts of patients can be
      combined using new research criteria for FTLD and demonstrate striking
      demographic differences among FTLD subgroups. The sex and age-at-onset
      differences suggest that there may be biological differences among FTLD
      subgroups. In this sample, FTLD with ubiquitin-positive inclusions accounted for
      half of all neuropathological diagnoses.

PMID- 15956164
TI  - Posterior cerebral artery infarction from middle cerebral artery infarction.
AB  - BACKGROUND: While it is known that posterior cerebral artery (PCA) infarction may
      simulate middle cerebral artery (MCA) infarction, the frequency and localization
      of this occurrence are unknown. OBJECTIVE: To determine the frequency of PCA
      infarction mimicking MCA infarction and the territory of the PCA most commonly
      involved in this simulation. DESIGN: We studied 202 patients with isolated
      infarction in the PCA admitted to our stroke center to determine the frequency of
      PCA infarction simulating MCA infarction, the involved PCA territory, and the
      patterns of clinical presentation. RESULTS: We found 36 patients (17.8%) with PCA
      ischemic stroke who had clinical features suggesting MCA stroke. The PCA
      territory most commonly involved was the superficial PCA territory (66.7%),
      followed by the proximal PCA territory (16.7%) and both the proximal and the
      superficial PCA territories (16.7%). The principal stroke mechanism was
      cardioembolic (54.1%) in the superficial PCA territory, lacunar (46.2%) in the
      proximal PCA territory, and undetermined (40.2%) in both the proximal and the
      superficial territories. Among the 36 patients, the most common clinical
      associations were aphasia (13 patients), visuospatial neglect (13 patients), and
      severe hemiparesis (7 patients). CONCLUSIONS: Posterior cerebral artery
      infarction simulating MCA infarction is more common than previously thought.
      Early recognition of the different stroke subtypes in these 2 arteries may allow
      specific management.

PMID- 15956165
TI  - Regional reductions in serotonin 1A receptor binding in juvenile myoclonic
      epilepsy.
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME) is classified as primarily
      generalized epilepsy and as such is assumed to lack an anatomic substrate.
      Although neurochemical abnormalities are probable, few studies have investigated
      whether they exist in JME. Animal data and the high incidence of myoclonic
      seizures in serotonin-intoxicated patients suggest that the serotonin system may
      be disturbed in JME. OBJECTIVE: To test the hypothesis that JME is associated
      with a disturbed serotonin system and that this disturbance could be reflected in
      altered serotonin 1A receptor binding. DESIGN: The serotonin 1A receptor binding
      potential (BP) was measured with positron emission tomography and serotonin 1A
      receptor antagonist carbonyl-carbon 11-WAY-100635. The BP was calculated using a
      reference tissue model in several limbic and neocortical regions and the raphe
      nuclei. SETTING: Epilepsy clinics of the Karolinska University Hospital,
      Stockholm, Sweden. PATIENTS: Eleven patients with JME and 11 controls were
      studied. MAIN OUTCOME MEASURE: Serotonin 1A receptor BP calculated in a set of
      volumes of interest. RESULTS: The patients with JME showed a reduced BP in the
      dorsolateral prefrontal cortex, raphe nuclei, and hippocampus. CONCLUSIONS: The
      observed reductions in serotonin 1A receptor BP suggest that the serotonin system
      is affected in JME. Although the data give no definitive information about
      underlying mechanisms, they provide a strong argument for the view that not all
      brain regions are homogeneously involved in this condition, further questioning
      the current classification of primarily generalized epilepsy.

PMID- 15956166
TI  - Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive
      impairment.
AB  - BACKGROUND: Subjects with mild cognitive impairment (MCI) have been shown to have
      reduced hippocampal volumes relative to normal elderly control subjects. The
      presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated
      with greater hippocampal atrophy in women than in men with Alzheimer disease.
      This relationship has not been demonstrated in MCI. OBJECTIVE: To examine the
      relationship between APOE genotype and hippocampal volume in men and women with
      MCI. DESIGN: This study evaluated MCI in 193 subjects (86 women and 107 men)
      participating in a multicenter clinical trial, all of whom underwent magnetic
      resonance imaging at their baseline visit. We evaluated the association among the
      number of APOE*E4 alleles, memory performance, and hippocampal volume in men and
      women with tests of means and multiple linear regressions. RESULTS: Compared with
      MCI subjects with no APOE*E4 alleles, women with 1 or 2 APOE*E4 alleles were
      found to have significantly reduced hippocampal volume, whereas men only showed a
      significant reduction in hippocampal volume when carrying 2 APOE*E4 alleles.
      Worsening of performance on a delayed word recall task (Alzheimer's Disease
      Assessment Scale cognitive subscale) showed an identical pattern in association
      with APOE*E4 allele dose and sex. Furthermore, when controlling for memory
      performance on delayed word recall, the APOE*E4 effect on hippocampal volumes was
      attenuated in men, but remained significant in women. CONCLUSION: The APOE*E4
      genotype status appears to have a greater deleterious effect on gross hippocampal
      pathology and memory performance in women than in men.

PMID- 15956167
TI  - FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in
      multiple system atrophy.
AB  - BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), a novel disorder
      in male carriers of premutations of the fragile X mental retardation 1 gene
      (FMR1), was recently described. The clinical presentation of FXTAS most closely
      resembles multiple system atrophy (MSA) because both disorders manifest with
      cerebellar ataxia, intention tremor, autonomic dysfunction, and parkinsonism. It
      has been proposed that FXTAS might be a common neurodegenerative disorder.
      OBJECTIVE: To determine whether FXTAS accounts for patients currently diagnosed
      as having MSA or a related clinical diagnosis. DESIGN: Patients with MSA or
      related phenotypes were examined by experienced movement disorders neurologists,
      and DNA samples were obtained for genetic study. SETTING: Salpetriere Hospital.
      PATIENTS: Seventy-seven patients clinically diagnosed as having MSA, 19 as having
      olivopontocerebellar atrophy, and 27 as having cerebellar ataxia. MAIN OUTCOME
      MEASURE: The number of FMR1 repeats was determined in all patients by polymerase
      chain reaction. Alleles above 40 CGG repeats were controlled by Southern blot
      analysis. RESULTS: Two patients carried FMR1 premutations of 110 and 135 repeats:
      a man with a familial form of cerebellar ataxia and a woman diagnosed as having
      MSA-cerebellar type. In addition, 9 patients (7%) carried alleles in the
      intermediate size range, from 41 to 53 repeats. CONCLUSIONS: We confirm the
      recent initial description of FXTAS in women. Our data suggest that FXTAS is rare
      in MSA and indicate that FXTAS might be less prevalent than proposed.

PMID- 15956168
TI  - Brain gamma-aminobutyric acid changes in stiff-person syndrome.
AB  - BACKGROUND: Patients with stiff-person syndrome (SPS) have circulating antibodies
      against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the
      synthesis of gamma-aminobutyric acid (GABA). Although the patients' symptoms of
      stiffness and unexpected spasms can be explained on the basis of reduced or
      impaired inhibitory neurotransmitters, such as GABA, it is unclear whether the
      level of GABA in the brains of these patients is reduced and, if so, whether the
      reduction is due to anti-glutamic acid decarboxylase antibodies. OBJECTIVE: To
      measure GABA levels in the brains of patients with SPS. DESIGN: Prospective case
      control study. SETTING: National Institute of Neurological Disorders and Stroke,
      National Institutes of Health, Bethesda, Md. PATIENTS: Eight patients with SPS
      with high titers of circulating anti-glutamic acid decarboxylase antibodies and
      typical clinical symptoms of SPS and 16 control subjects. MAIN OUTCOME MEASURES:
      Results of brain magnetic resonance imaging and magnetic resonance spectroscopy,
      which measures GABA levels in specific brain regions. RESULTS: No abnormalities
      were noted on brain magnetic resonance images. A prominent and significant
      decrease in GABA level was, however, observed in the sensorimotor cortex and a
      smaller decrease in the posterior occipital cortex but not in the cingulate
      cortex or pons. CONCLUSIONS: The reduction of brain GABA in patients with SPS
      supports the clinical symptoms and indicates that the inhibitory GABAergic
      pathways are involved in the disease. Regardless of the responsible autoantigens,
      in SPS autoantibodies block the function of GABAergic neurons and interfere with
      the synthesis of GABA but do not cause structural changes in the brain.

PMID- 15956169
TI  - Predictive utility of apolipoprotein E genotype for Alzheimer disease in
      outpatients with mild cognitive impairment.
AB  - BACKGROUND: In cognitively impaired patients without dementia, the utility of
      apolipoprotein E (APOE) genotyping is unclear. OBJECTIVE: To evaluate the
      predictive utility of the APOE epsilon4 genotype for conversion to probable
      Alzheimer disease (AD). DESIGN: Naturalistic, longitudinal study. SETTING: Memory
      disorders outpatient clinic. PATIENTS: A total of 136 patients with memory
      complaints were determined to have mild cognitive impairment and were evaluated
      every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated
      annually. MAIN OUTCOME MEASURES: Primary outcome measures included conversion to
      AD. Secondary outcome measures included change over time in Mini-Mental State
      Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score.
      RESULTS: The APOE epsilon4 allele was present in 25% of patients and 21% of
      healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of
      136 patients converted to AD. APOE epsilon4 carrier status did not differ between
      converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the
      time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4
      homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a
      Cox proportional hazards model stratified by age quartiles, after controlling for
      sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased
      the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95%
      confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n
      = 79; P = .7). CONCLUSIONS: APOE epsilon4 carrier status was associated with
      conversion to AD in older outpatients after controlling for known demographic and
      clinical risk factors, and APOE epsilon4 homozygosity was associated with
      increased risk of conversion to AD. However, APOE epsilon4 carrier status by
      itself did not predict cognitive decline or conversion to AD, indicating that
      APOE genotyping in patients with mild cognitive impairment may have limited
      clinical applicability for prediction of outcome.

PMID- 15956170
TI  - Clinical and magnetic resonance imaging characteristics of sporadic cerebellar
      ataxia.
AB  - BACKGROUND: It is unknown whether multiple system atrophy of the cerebellar type
      (MSA-C) and idiopathic cerebellar ataxia with extracerebellar presentation (IDCA
      P) represent distinct entities. OBJECTIVE: To investigate the discriminative
      validity of magnetic resonance imaging in sporadic cerebellar ataxia. DESIGN:
      Basal ganglia and infratentorial structures were screened for signal
      abnormalities and atrophic changes. Magnetic resonance imaging raters were masked
      to the clinical diagnosis. SETTING: Outpatient clinic of a university hospital.
      PATIENTS: Forty-one individuals were diagnosed as having MSA-C (n = 30) or IDCA-P
      (n = 11) based on their clinical features. RESULTS: Shrinkage of the cerebellar
      vermis and hemispheres was found in both groups. Atrophy of the brainstem and
      middle cerebellar peduncles was significantly more frequent in patients with MSA
      C (P<.001). Hyperintensities of infratentorial structures were common in patients
      with MSA-C (middle cerebellar peduncles: 87%; pons: 97%) but were absent in
      patients with IDCA-P. Hypointensities or hyperintensities of basal ganglia
      structures did not reliably differentiate the groups. CONCLUSIONS: Patients with
      MSA-C were characterized by a higher frequency and severity of magnetic resonance
      imaging abnormalities (atrophic changes and additional hyperintense signal
      changes) of the middle cerebellar peduncles and pons. The presence of these
      magnetic resonance imaging features points to the diagnosis of MSA-C and helps
      differentiate MSA-C from other types of sporadic cerebellar ataxia with
      extracerebellar features.

PMID- 15956171
TI  - The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis.
AB  - BACKGROUND: Late-onset GM2 gangliosidosis (LGG) is a rare disease that is often
      considered in the differential diagnosis of adolescents and young adults who
      present with multiple realms of neurologic dysfunction. Cognitive disturbances
      are common but have not been systematically studied. OBJECTIVE: To determine the
      natural history of cognitive dysfunction in patients with LGG. DESIGN: Case
      series and literature review. SETTING: Urban tertiary referral clinic. PATIENTS:
      Individuals with hexosaminidase A deficiency as the origin of LGG. MAIN OUTCOME
      MEASURES: Cognitive dysfunction, psychiatric symptoms, and cerebellar, upper
      motor neuron, lower motor neuron, or extrapyramidal symptoms and signs. RESULTS:
      Historical and examination data from 62 patients were found. Forty-four percent
      of LGG patients had some degree of cognitive dysfunction. Cognitive dysfunction
      was associated with a greater number of other elemental neurologic deficits. In
      21 patients with acceptable longitudinal information, 8 (38%) had a static
      cognitive disorder, whereas progressive dementia was evident in 13 patients
      (62%), including 2 of our cases with serial neuropsychological testing.
      Neuroimaging often showed nonspecific cerebellar and/or cerebral atrophy.
      CONCLUSIONS: Cognitive dysfunction is a frequent manifestation of LGG. Patients
      who experience cognitive dysfunction are more likely to have a greater number of
      other neurologic manifestations of the disease. Cognitive dysfunction may take
      the form of static encephalopathy, but progressive dementia is more often
      encountered. The pathogenesis of cognitive dysfunction in this disease is
      unknown, highlighting the need for further study.

PMID- 15956172
TI  - Monozygotic twins discordant for Huntington disease after 7 years.
AB  - BACKGROUND: Huntington disease (HD) has only rarely been identified in identical
      twins. All described twins have had disease onset within 1 year of each other,
      suggesting that disease onset is determined solely by genetic influences.
      OBJECTIVE: To describe a unique set of monozygotic twins in whom clinical HD
      onset is at least 7 years apart. DESIGN: A 71-year-old woman was diagnosed as
      having HD based on medical history, physical examination results consistent with
      HD, and a CAG trinucleotide repeat number of 39 in the HD gene on chromosome 4.
      Her onset was 6 years earlier. Her genetically confirmed identical twin, carrying
      the same number of CAG repeats, was neurologically healthy when examined the next
      year. Only the HD-manifest twin had chronic bronchitis, rheumatoid arthritis,
      type 2 diabetes mellitus, and chronic anemia. Both had hypertension. CONCLUSIONS:
      To our knowledge, this is the first report of monozygotic twins discordant for HD
      by more than 2 years. The onset of HD symptoms in a patient with 39 triplet
      repeats at least 7 years earlier than her identical twin suggests the possibility
      that the disease may be initiated (or delayed) by environmental factors. We have
      identified increased cigarette use and longer exposure to various industrial
      toxins as potential explanations for the earlier onset in one twin.

PMID- 15956173
TI  - Anti-MuSK myasthenia gravis presenting with purely ocular findings.
AB  - BACKGROUND: Antibodies to a muscle-specific receptor tyrosine kinase (MuSK) have
      been found in approximately 40% of patients with generalized myasthenia gravis
      who are seronegative for the antiacetylcholine receptor antibody. Many of the
      patients with anti-MuSK antibodies have prominent oculobulbar symptoms or
      weakness of the neck and respiratory muscles, but patients with ocular myasthenia
      have not been described. OBJECTIVE: To report a case of ocular myasthenia due to
      anti-MuSK antibodies. PATIENT: A young woman with ocular myasthenia and
      antibodies to MuSK. RESULTS: Anti-MuSK antibody was detected by radioimmunoassay
      using highly purified MuSK recombinant antigen. CONCLUSION: Ocular myasthenia
      gravis is a presentation of the anti-MuSK antibody syndrome.

PMID- 15956174
TI  - Essential tremor associated with focal nonnigral Lewy bodies: a clinicopathologic
      study.
AB  - BACKGROUND: Essential tremor is one of the most common neurological diseases. Its
      links with Parkinson disease (PD) are often debated. There have been few
      published postmortem studies. OBJECTIVE: To study our first case of essential
      tremor through the recently established Essential Tremor Centralized Brain
      Repository. DESIGN: Report of a case of a patient with a diagnosis of severe
      essential tremor for 46 years who exhibited no signs of parkinsonism. RESULTS: On
      postmortem examination, gross brain sections showed no abnormalities. Results of
      microscopic examination of hematoxylin-eosin-stained sections revealed that the
      locus coeruleus contained multiple Lewy bodies (LBs), although none were found in
      the substantia nigra, dorsal vagal nuclei, thalamus, substantia innominata,
      inferior olivary nucleus, or cerebellum. Immunochemical staining using antibodies
      directed against alpha-synuclein confirmed the presence of many LBs in the locus
      ceruleus and showed rare LBs in the substantia innominata and dorsal vagal
      nuclei. There were no LBs in the substantia nigra. CONCLUSIONS: Our patient had a
      very focal presence of LBs in the locus ceruleus, an anatomically restricted form
      of LB disease. This study provides support for the link between essential tremor
      and LB disease and raises the question as to what proportion of patients with
      essential tremor might have unusual forms of LB disease.

PMID- 15956175
TI  - Seizures and cerebral schistosomiasis.
AB  - BACKGROUND: Schistosoma mansoni is a parasitic trematoid worm that infects
      humans. Schistosomiasis is endemic in parts of South America, sub-Saharan Africa,
      the Middle East, and some Caribbean islands. Disorders of the liver and
      gastrointestinal tract are the most common clinical manifestations. The central
      nervous system is not usually affected. The most common neurologic manifestation
      is transverse myelitis. In some circumstances, the eggs of S. mansoni are found
      in the brain, causing inflammatory reaction. OBJECTIVE: To describe a young
      Brazilian patient with partial epileptic seizures caused by a granulomatous
      lesion due to S. mansoni. CONCLUSION: In endemic areas or in patients with a
      positive epidemiological history, schistosomiasis must be considered as a
      possible diagnosis of seizures, particularly when they are associated with
      granulomatous lesions on magnetic resonance imaging.

PMID- 15956176
TI  - Idiopathic transverse myelitis.

PMID- 15956177
TI  - Magnetic resonance imaging findings in a patient with bilateral limbic
      encephalitis.

PMID- 15956178
TI  - Ring-enhancing lesion in central pontine myelinolysis.

PMID- 15956179
TI  - Ventricular obstruction from neurocysticercosis.

PMID- 15956181
TI  - Atomic-scale dynamical structures of fatty acid bilayers observed by ultrafast
      electron crystallography.
AB  - The structure and dynamics of a biological model bilayer are reported with atomic
      scale resolution by using ultrafast electron crystallography. The bilayer was
      deposited as a Langmuir-Blodgett structure of arachidic (eicosanoic) fatty acids
      with the two chains containing 40 carbon atoms (approximately = 50 angstroms), on
      a hydrophobic substrate, the hydrogen terminated silicon(111) surface. We
      determined the structure of the 2D assembly, establishing the orientation of the
      chains and the subunit cell of the CH2 distances: a0 = 4.7 angstroms, b0 = 8.0
      angstroms, and c0 = 2.54 angstroms. For structural dynamics, the diffraction
      frames were taken every 1 picosecond after a femtosecond temperature jump. The
      observed motions, with sub-angstroms resolution and monolayer sensitivity,
      clearly indicate the coherent anisotropic expansion of the bilayer solely along
      the aliphatic chains, followed by nonequilibrium contraction and restructuring at
      longer times. This motion is indicative of a nonlinear behavior among the
      anharmonically coupled bonds on the ultrashort time scale and energy
      redistribution and diffusion on the longer time scale. The ability to observe
      such atomic motions of complex structures and at interfaces is a significant leap
      forward for the determination of macromolecular dynamical structures by using
      ultrafast electron crystallography.

PMID- 15956182
TI  - Severe acute respiratory syndrome (SARS) S protein production in plants:
      development of recombinant vaccine.
AB  - In view of a recent spread of severe acute respiratory syndrome (SARS), there is
      a high demand for production of a vaccine to prevent this disease. Recent studies
      indicate that SARS-coronavirus (CoV) spike protein (S protein) and its truncated
      fragments are considered the best candidates for generation of the recombinant
      vaccine. Toward the development of a safe, effective, and inexpensive vaccine
      candidate, we have expressed the N-terminal fragment of SARS-CoV S protein (S1)
      in tomato and low-nicotine tobacco plants. Incorporation of the S1 fragment into
      plant genomes as well as its transcription was confirmed by PCR and RT-PCR
      analyses. High levels of expression of recombinant S1 protein were observed in
      several transgenic lines by Western blot analysis using specific antibodies.
      Plant-derived antigen was evaluated to induce the systemic and mucosal immune
      responses in mice. Mice showed significantly increased levels of SARS-CoV
      specific IgA after oral ingestion of tomato fruits expressing S1 protein. Sera of
      mice parenterally primed with tobacco-derived S1 protein revealed the presence of
      SARS-CoV-specific IgG as detected by Western blot and ELISA analysis.

PMID- 15956183
TI  - NMR study of a membrane protein in detergent-free aqueous solution.
AB  - One of the major obstacles to membrane protein (MP) structural studies is the
      destabilizing effect of detergents. Amphipols (APols) are short amphipathic
      polymers that can substitute for detergents to keep MPs water-soluble under mild
      conditions. In the present work, we have explored the feasibility of studying the
      structure of APol-complexed MPs by NMR. As a test MP, we chose the 171-residue
      transmembrane domain of outer MP A from Escherichia coli (tOmpA), whose x-ray and
      NMR structures in detergent are known. 2H,15N-labeled tOmpA was produced as
      inclusion bodies, refolded in detergent solution, trapped with APol A8-35, and
      the detergent removed by adsorption onto polystyrene beads. The resolution of
      transverse relaxation-optimized spectroscopy-heteronuclear single-quantum
      correlation spectra of tOmpA/A8-35 complexes was found to be close to that of the
      best spectra obtained in detergent solutions. The dispersion of chemical shifts
      indicated that the protein had regained its native fold and retained it during
      the exchange of surfactants. MP-APol interactions were mapped by substituting
      hydrogenated for deuterated A8-35. The resulting dipolar broadening of amide
      proton linewidths was found to be limited to the beta-barrel region of tOmpA,
      indicating that A8-35 binds specifically to the hydrophobic transmembrane surface
      of the protein. The potential of this approach to MP studies by solution NMR is
      discussed.

PMID- 15956184
TI  - Longitudinal analysis of the group A Streptococcus transcriptome in experimental
      pharyngitis in cynomolgus macaques.
AB  - Identification of the genetic events that contribute to host-pathogen
      interactions is important for understanding the natural history of infectious
      diseases and developing therapeutics. Transcriptome studies conducted on
      pathogens have been central to this goal in recent years. However, most of these
      investigations have focused on specific end points or disease phases, rather than
      analysis of the entire time course of infection. To gain a more complete
      understanding of how bacterial gene expression changes over time in a primate
      host, the transcriptome of group A Streptococcus (GAS) was analyzed during an 86
      day infection protocol in 20 cynomolgus macaques with experimental pharyngitis.
      The study used 260 custom Affymetrix (Santa Clara, CA) chips, and data were
      confirmed by TaqMan analysis. Colonization, acute, and asymptomatic phases of
      disease were identified. Successful colonization and severe inflammation were
      significantly correlated with an early onset of superantigen gene expression. The
      differential expression of two-component regulators covR and spy0680 (M1_spy0874)
      was significantly associated with GAS colony-forming units, inflammation, and
      phases of disease. Prophage virulence gene expression and prophage induction
      occurred predominantly during high pathogen cell densities and acute
      inflammation. We discovered that temporal changes in the GAS transcriptome were
      integrally linked to the phase of clinical disease and host-defense response.
      Knowledge of the gene expression patterns characterizing each phase of pathogen
      host interaction provides avenues for targeted investigation of proven and
      putative virulence factors and genes of unknown function and will assist vaccine
      research.

PMID- 15956185
TI  - Time-varying covariance of neural activities recorded in striatum and frontal
      cortex as monkeys perform sequential-saccade tasks.
AB  - Cortico-basal ganglia circuits are key parts of the brain's habit system, but
      little is yet known about how these forebrain pathways function as ingrained
      habits are performed. We simultaneously recorded spike and local field potential
      (LFP) activity from regions of the frontal cortex and basal ganglia implicated in
      visuo-oculomotor control as highly trained macaque monkeys performed sequences of
      visually guided saccades. The tasks were repetitive, required no new learning,
      and could be performed nearly automatically. Our findings demonstrate striking
      differences between the relative timing of striatal and cortical activity during
      performance of the tasks. At the onset of the visual cues, LFPs in the prefrontal
      cortex and the oculomotor zone of the striatum showed near-synchronous
      activation. During the period of sequential-saccade performance, however, peak
      LFP activity occurred 100-300 msec later in the striatum than in the prefrontal
      cortex. Peak prefrontal activity tended to be peri-saccadic, whereas peak
      striatal activity tended to be post-saccadic. This temporal offset was also
      apparent in pairs of simultaneously recorded prefrontal and striatal neurons. In
      triple-site recordings, the LFP activity recorded in the supplementary eye field
      shared temporal characteristics of both the prefrontal and the striatal patterns.
      The near simultaneity of prefrontal and striatal peak responses at cue onsets,
      but temporal lag of striatal activity in the movement periods, suggests that the
      striatum may integrate corollary discharge or confirmatory response signals
      during sequential task performance. These timing relationships may be signatures
      of the normal functioning of striatal and frontal cortex during repetitive
      performance of learned behaviors.

PMID- 15956186
TI  - Identification of a major restriction in HIV-1 intersubtype recombination.
AB  - Genetic recombination increases diversity in HIV-1 populations, thereby allowing
      variants to escape from host immunity or antiviral therapies. In addition to the
      currently described nine subtypes of HIV-1, many of the circulating strains are
      intersubtype recombinants. In this study, we determined the recombination rate
      between two HIV-1 subtype C viruses and between a subtype B virus and a subtype C
      virus during a single round of virus replication. Although HIV-1 subtype C
      recombines at a high rate, similar to that of HIV-1 subtype B, the recombination
      rate between a subtype B virus and a subtype C virus is much lower than the
      intrasubtype recombination rate. A 3-nt sequence difference in the dimerization
      initiation signal (DIS) region between HIV-1 subtypes B and C accounts for most
      of the reduction of intersubtype recombination. By matching the DIS sequences,
      the B/C intersub-type recombination rate was elevated 4-fold; by introducing
      mismatches in the 3-nt sequences, the B/B intrasubtype recombination rate was
      reduced 4-fold. Further analyses showed that the intermolecular template
      switching frequency was unaffected by the sequence identity of the DIS region.
      These results support the hypothesis that mismatched sequences in the DIS region
      alter the formation of heterozygous virions, thereby lowering the observable
      recombination rate. Here, we present the discovery of a major restriction in HIV
      1 intersubtype recombination. These results have important implications for virus
      evolution, the mechanism of HIV-1 RNA packaging, high negative interference in
      recombination, and the generation of circulating intersubtype recombinants within
      the infected population.

PMID- 15956187
TI  - Collecting duct-specific deletion of peroxisome proliferator-activated receptor
      gamma blocks thiazolidinedione-induced fluid retention.
AB  - The peroxisome proliferator-activated receptor subtype gamma (PPARgamma) ligands,
      namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have
      demonstrated great potential in the treatment of type II diabetes. However, their
      clinical applicability is limited by a common and serious side effect of edema.
      To address the mechanism of TZD-induced edema, we generated mice with collecting
      duct (CD)-specific disruption of the PPARgamma gene. We found that mice with CD
      knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced
      increases in body weight and plasma volume expansion found in control mice
      expressing PPARgamma in the CD. RGZ reduced urinary sodium excretion in control
      and not in conditional knockout mice. Furthermore, RGZ stimulated sodium
      transport in primary cultures of CD cells expressing PPARgamma and not in cells
      lacking this receptor. These findings demonstrate a PPARgamma-dependent pathway
      in regulation of sodium transport in the CD that underlies TZD-induced fluid
      retention.

PMID- 15956188
TI  - Charge transport in DNA in solution: the role of polarons.
AB  - Since the discovery a decade ago of rapid photoinduced electron transfer in DNA
      over a distance >4 nm, a large number of experiments and theories have been
      advanced in the attempt to characterize the transfer, mainly of a radical cation
      or hole. Particularly influential experiments were carried out by Giese [Giese,
      B. (2000) Acc. Chem. Res. 33, 631-636] on the sequence G(A)(n)GGG, where G is
      guanine and A is adenine. These experiments were interpreted as showing that for
      n > 3, after the holes tunnel through the first three As, they hop onto the
      bridge of As, where they are localized on a single A and travel further by
      hopping between neighboring As. Recent experiments of Barton and coworkers [Shao,
      F., O'Neill, M. A. & Barton, J. K. (2004) Proc. Natl. Acad. Sci. USA 101, 17914
      17919] have, however, established that the hole wavefunctions are delocalized.
      One of the mechanisms based on delocalized hole wavefunctions that had been
      investigated, both experimentally and theoretically, is transport by polarons.
      For one type of polaron, the properties are determined by polarization of the
      surrounding medium (water and ions, in this case). Theory predicts that this type
      of polaron is delocalized over approximately four bases in DNA. Transport by
      these polarons could explain the results of Giese et al. [Giese, B., Amaudrut,
      J., Kohler, A.-K., Spormann, M. & Wessely, S. (2001) Nature 412, 318-320], recent
      experimental results of O'Neill and Barton [O'Neill, M. A. & Barton, J. K. (2004)
      J. Am. Chem. Soc. 126, 11471-11483] concerning the size of the region over which
      the hole is delocalized, and other experimental observations.

PMID- 15956189
TI  - Tunneling rates in electron transport through double-barrier molecular junctions
      in a scanning tunneling microscope.
AB  - The scanning tunneling microscope enables atomic-scale measurements of electron
      transport through individual molecules. Copper phthalocyanine and magnesium
      porphine molecules adsorbed on a thin oxide film grown on the NiAl(110) surface
      were probed. The single-molecule junctions contained two tunneling barriers,
      vacuum gap, and oxide film. Differential conductance spectroscopy shows that
      electron transport occurs via vibronic states of the molecules. The intensity of
      spectral peaks corresponding to the individual vibronic states depends on the
      relative electron tunneling rates through the two barriers of the junction, as
      found by varying the vacuum gap tunneling rate by changing the height of the
      scanning tunneling microscope tip above the molecule. A simple, sequential
      tunneling model explains the observed trends.

PMID- 15956190
TI  - Scanning tunneling microscopy experiments on single molecular landers.
AB  - Molecular landers are molecules comprising of a central rigid molecular wire
      maintained above a metallic surface by organic spacers, which allows specific
      ultrahigh vacuum-scanning tunneling microscopy experiments to be performed at the
      single-molecule level. The understanding of the molecule-surface interactions,
      intramolecular mechanics, and the possibility to perform extremely precise tip
      induced manipulation permit these molecules to be brought in contact with a
      nanoelectrode and the resulting electronic interaction to be analyzed in well
      controlled conditions.

PMID- 15956191
TI  - Rapid plasticity of binocular connections in developing monkey visual cortex
      (V1).
AB  - The basic sets of cortical connections are present at birth in the primate visual
      system. The maintenance and refinement of these innate connections are highly
      dependent on normal visual experience, and prolonged exposure to binocularly
      uncorrelated signals early in life severely disrupts the normal development of
      binocular functions. However, very little is known about how rapidly these
      changes in the functional organization of primate visual cortex emerge or what
      are the sequence and the nature of the abnormal neural events that occur
      immediately after experiencing binocular decorrelation. In this study, we
      investigated how brief periods of ocular misalignment (strabismus) at the height
      of the critical period alter the cortical circuits that support binocular vision.
      After only 3 days of optically imposed strabismus, there was a striking increase
      in the prevalence of V1 neurons that exhibited binocular suppression, i.e.,
      binocular responses were weaker than monocular responses. However, the
      sensitivity of these neurons to interocular spatial phase disparity was not
      significantly altered. These contrasting results suggest that the first
      significant change in V1 caused by early binocular decorrelation is binocular
      suppression, and that this suppression originates at a site(s) beyond where
      binocular signals are initially combined.

PMID- 15956192
TI  - Molecular electronics: some views on transport junctions and beyond.
AB  - The field of molecular electronics comprises a fundamental set of issues
      concerning the electronic response of molecules as parts of a mesoscopic
      structure and a technology-facing area of science. We will overview some
      important aspects of these subfields. The most advanced ideas in the field
      involve the use of molecules as individual logic or memory units and are broadly
      based on using the quantum state space of the molecule. Current work in molecular
      electronics usually addresses molecular junction transport, where the molecule
      acts as a barrier for incoming electrons: This is the fundamental Landauer idea
      of "conduction as scattering" generalized to molecular junction structures.
      Another point of view in terms of superexchange as a guiding mechanism for
      coherent electron transfer through the molecular bridge is discussed. Molecules
      generally exhibit relatively strong vibronic coupling. The last section of this
      overview focuses on vibronic effects, including inelastic electron tunneling
      spectroscopy, hysteresis in junction charge transport, and negative differential
      resistance in molecular transport junctions.

PMID- 15956193
TI  - Probing pi-coupling in molecular junctions.
AB  - Charge transport characteristics for metal-molecule-metal junctions containing
      two structurally related pi-conjugated systems were studied to probe pi-pi
      interactions in molecular junctions. The first molecule contains a typical pi
      conjugated framework derived from phenylene vinylene units, whereas the second
      has the phenylene vinylene structure interrupted by a [2.2]paracyclophane (pCp)
      core. Electrochemical investigations were used to characterize the defects and
      packing density of self-assembled monolayers of the two molecules on gold
      surfaces and to enable quantitative comparison of their transport
      characteristics. Current-voltage measurements across molecular junctions
      containing the two species demonstrate that the pCp moiety yields a highly
      conductive break in through-bond pi-conjugation. The observed high conductivity
      is consistent with density functional theory calculations, which demonstrate
      strong through-space pi-pi coupling across the pCp moiety.

PMID- 15956194
TI  - Climatically driven macroevolutionary patterns in the size of marine diatoms over
      the Cenozoic.
AB  - Numerous taxonomic groups exhibit an evolutionary trajectory in cell or body
      size. The size structure of marine phytoplankton communities strongly affects
      food web structure and organic carbon export into the ocean interior, yet
      macroevolutionary patterns in the size structure of phytoplankton communities
      have not been previously investigated. We constructed a database of the size of
      the silica frustule of the dominant fossilized marine planktonic diatom species
      over the Cenozoic. We found that the minimum and maximum sizes of the diatom
      frustule have expanded in concert with increasing species diversity. In contrast,
      the mean area of the diatom frustule is highly correlated with oceanic
      temperature gradients inferred from the delta18O of foraminiferal calcite,
      consistent with the hypothesis that climatically induced changes in oceanic
      mixing have altered nutrient availability in the euphotic zone and driven
      macroevolutionary shifts in the size of marine pelagic diatoms through the
      Cenozoic.

PMID- 15956195
TI  - The cysteine-rich region of respiratory syncytial virus attachment protein
      inhibits innate immunity elicited by the virus and endotoxin.
AB  - The attachment protein (glycoprotein) of respiratory syncytial virus (RSV) has
      long been associated with disease potentiation and respiratory symptoms. The
      glycoprotein has a conserved cysteine-rich region (GCRR) whose function is
      unknown and which is not necessary for efficient viral replication. In this
      report, we show that the GCRR is a powerful inhibitor of the innate immune
      response against RSV, and that early secretion of glycoprotein is critical to
      modulate inflammation after RSV infection. Importantly, the GCRR is also a potent
      inhibitor of cytokine production mediated by several TLR agonists, indicating
      that this peptide sequence displays broad antiinflammatory properties. These
      findings have important implications for RSV pathogenesis and describe an
      inhibitor of TLR-mediated inflammatory responses that could have clinical
      applications.

PMID- 15956196
TI  - Swe1 regulation and transcriptional control restrict the activity of mitotic
      cyclins toward replication proteins in Saccharomyces cerevisiae.
AB  - Cyclin-dependent kinases (CDKs) drive the cell cycle through the phosphorylation
      of substrates that function in genome duplication and cell division. The
      existence of multiple cyclin subunits and their distinct cell cycle-regulated
      expression suggests that cyclins impart unique specificities to CDK-substrate
      interactions that are critical for normal cellular function. This study shows
      that the combination of early cell cycle expression and deletion of the CDK
      inhibitor Saccharomyces Wee1 (Swe1) enables the mitotic B-type (Clb) cyclins
      Clb2, Clb3, and Clb4 of Saccharomyces cerevisiae to initiate S phase with similar
      effectiveness as the S-phase cyclin Clb5. Although in vivo analysis indicates
      preferential phosphorylation of a replication substrate by Clb5-Cdk1, this
      difference is relatively minor compared with the impact of transcriptional
      control and Swe1 regulation. Indeed, early expressed Clb2-Cdk1 can activate all
      essential Clb-Cdk substrates in a strain lacking all other Clbs and Swe1. Thus,
      Swe1 regulation and expression timing are key mechanisms that sequester the broad
      activity of Clb2-Cdk1 from critical substrates. Furthermore, the ability of Swe1
      to inhibit the activity of different B-type cyclins in replication initiation
      correlates with the normal expression timing of those cyclins, with no apparent
      in vivo inhibition of Clb5 and Clb6, moderate inhibition of Clb3 and Clb4, and
      strong inhibition of Clb2. Hence, Swe1 appears to reinforce the temporal activity
      of cyclins established through transcriptional control. The conserved nature of
      CDK function suggests that similar mechanisms regulate CDK specificity in
      multicellular organisms.

PMID- 15956197
TI  - Diversifying the repertoire of G protein-coupled receptors through
      oligomerization.

PMID- 15956198
TI  - Gene duplication and the origin of novel proteins.

PMID- 15956199
TI  - Premature ovarian aging in mice deficient for Gpr3.
AB  - After becoming competent for resuming meiosis, fully developed mammalian oocytes
      are maintained arrested in prophase I until ovulation is triggered by the
      luteotropin surge. Meiotic pause has been shown to depend critically on
      maintenance of cAMP level in the oocyte and was recently attributed to the
      constitutive Gs (the heterotrimeric GTP-binding protein that activates adenylyl
      cyclase) signaling activity of the G protein-coupled receptor GPR3. Here we show
      that mice deficient for Gpr3 are unexpectedly fertile but display progressive
      reduction in litter size despite stable age-independent alteration of meiotic
      pause. Detailed analysis of the phenotype confirms premature resumption of
      meiosis, in vivo, in about one-third of antral follicles from Gpr3-/- females,
      independently of their age. In contrast, in aging mice, absence of GPR3 leads to
      severe reduction of fertility, which manifests by production of an increasing
      number of nondeveloping early embryos upon spontaneous ovulation and massive
      amounts of fragmented oocytes after superovulation. Severe worsening of the
      phenotype in older animals points to an additional role of GPR3 related to
      protection (or rescue) of oocytes from aging. Gpr3-defective mice may constitute
      a relevant model of premature ovarian failure due to early oocyte aging.

PMID- 15956200
TI  - Fire cycles in North American interior grasslands and their relation to prairie
      drought.
AB  - High-resolution analyses of a late Holocene core from Kettle Lake in North Dakota
      reveal coeval fluctuations in loss-on-ignition carbonate content, percentage of
      grass pollen, and charcoal flux. These oscillations are indicative of climate
      fuel-fire cycles that have prevailed on the Northern Great Plains (NGP) for most
      of the late Holocene. High charcoal flux occurred during past moist intervals
      when grass cover was extensive and fuel loads were high, whereas reduced charcoal
      flux characterized the intervening droughts when grass cover, and hence fuel
      loads, decreased, illustrating that fire is not a universal feature of the NGP
      through time but oscillates with climate. Spectral and wavelet analyses reveal
      that the cycles have a periodicity of approximately = 160 yr, although secular
      trends in the cycles are difficult to identify for the entire Holocene because
      the periodicity in the early Holocene ranged between 80 and 160 yr. Although the
      cycles are evident for most of the last 4,500 yr, their occasional muting adds
      further to the overall climatic complexity of the plains. These findings clearly
      show that the continental interior of North America has experienced short-term
      climatic cycles accompanied by a marked landscape response for several millennia,
      regularly alternating between dual landscape modes. The documentation of cycles
      of similar duration at other sites in the NGP, western North America, and
      Greenland suggests some degree of regional coherence to climatic forcing.
      Accordingly, the effects of global warming from increasing greenhouse gases will
      be superimposed on this natural variability of drought.

PMID- 15956201
TI  - Phenotype-genotype correlation in Hirschsprung disease is illuminated by
      comparative analysis of the RET protein sequence.
AB  - The ability to discriminate between deleterious and neutral amino acid
      substitutions in the genes of patients remains a significant challenge in human
      genetics. The increasing availability of genomic sequence data from multiple
      vertebrate species allows inclusion of sequence conservation and physicochemical
      properties of residues to be used for functional prediction. In this study, the
      RET receptor tyrosine kinase serves as a model disease gene in which a broad
      spectrum (> or = 116) of disease-associated mutations has been identified among
      patients with Hirschsprung disease and multiple endocrine neoplasia type 2. We
      report the alignment of the human RET protein sequence with the orthologous
      sequences of 12 non-human vertebrates (eight mammalian, one avian, and three
      teleost species), their comparative analysis, the evolutionary topology of the
      RET protein, and predicted tolerance for all published missense mutations. We
      show that, although evolutionary conservation alone provides significant
      information to predict the effect of a RET mutation, a model that combines
      comparative sequence data with analysis of physiochemical properties in a
      quantitative framework provides far greater accuracy. Although the ability to
      discern the impact of a mutation is imperfect, our analyses permit substantial
      discrimination between predicted functional classes of RET mutations and disease
      severity even for a multigenic disease such as Hirschsprung disease.

PMID- 15956202
TI  - Evasion of Toll-like receptor 5 by flagellated bacteria.
AB  - Toll-like receptor 5 (TLR5) recognizes an evolutionarily conserved site on
      bacterial flagellin that is required for flagellar filament assembly and
      motility. The alpha and epsilon Proteobacteria, including the important human
      pathogens Campylobacter jejuni, Helicobacter pylori, and Bartonella
      bacilliformis, require flagellar motility to efficiently infect mammalian hosts.
      In this study, we demonstrate that these bacteria make flagellin molecules that
      are not recognized by TLR5. We map the site responsible for TLR5 evasion to amino
      acids 89-96 of the N-terminal D1 domain, which is centrally positioned within the
      previously defined TLR5 recognition site. Salmonella flagellin is strongly
      recognized by TLR5, but mutating residues 89-96 to the corresponding H. pylori
      flaA sequence abolishes TLR5 recognition and also destroys bacterial motility. To
      preserve bacterial motility, alpha and epsilon Proteobacteria possess
      compensatory amino acid changes in other regions of the flagellin molecule, and
      we engineer a mutant form of Salmonella flagellin that evades TLR5 but retains
      motility. These results suggest that TLR5 evasion is critical for the survival of
      this subset of bacteria at mucosal sites in animals and raise the intriguing
      possibility that flagellin receptors provided the selective force to drive the
      evolution of these unique subclasses of bacterial flagellins.

PMID- 15956203
TI  - In vivo formation and repair of DNA double-strand breaks after computed
      tomography examinations.
AB  - Ionizing radiation can lead to a variety of deleterious effects in humans, most
      importantly to the induction of cancer. DNA double-strand breaks (DSBs) are among
      the most significant genetic lesions introduced by ionizing radiation that can
      initiate carcinogenesis. We have enumerated gamma-H2AX foci as a measure for DSBs
      in lymphocytes from individuals undergoing computed tomography examination of the
      thorax and/or the abdomen. The number of DSBs induced by computed tomography
      examination was found to depend linearly on the dose-length product, a
      radiodiagnostic unit that is proportional to both the local dose delivered and
      the length of the body exposed. Analysis of lymphocytes sampled up to 1 day
      postirradiation provided kinetics for the in vivo loss of gamma-H2AX foci that
      correlated with DSB repair. Interestingly, in contrast to results obtained in
      vitro, normal individuals repair DSBs to background levels. A patient who had
      previously shown severe side effects after radiotherapy displayed levels of gamma
      H2AX foci at various sampling times postirradiation that were several times
      higher than those of normal individuals. Gamma-H2AX and pulsed-field gel
      electrophoresis analysis of fibroblasts obtained from this patient confirmed a
      substantial DSB repair defect. Additionally, these fibroblasts showed significant
      in vitro radiosensitivity. These data show that the in vivo induction and repair
      of DSBs can be assessed in individuals exposed to low radiation doses, adding a
      further dimension to DSB repair studies and providing the opportunity to identify
      repair-compromised individuals after diagnostic irradiation procedures.

PMID- 15956204
TI  - Seeing what is not there shows the costs of perceptual learning.
AB  - Perceptual learning is an improvement in one's sensory abilities after training
      and is thought to help us to better adapt to the sensory environment. Here, we
      show that perceptual learning also can lead to misperceptions, such that subjects
      actually perceive stimuli when none are physically presented. After learning,
      subjects not only showed enhanced performance when tested with the motion
      direction of the trained stimulus but also often reported seeing dots moving in
      the trained direction when no stimulus was displayed. We further show that these
      misperceptions are not attributable to a response bias. These results show that
      there are costs as well as benefits to perceptual learning and that performance
      enhancements for a specific feature also can be accompanied by misperceptions of
      the visual environment.

PMID- 15956206
TI  - Vibrational inelastic scattering effects in molecular electronics.
AB  - We describe how to treat the interaction of traveling electrons with localized
      vibrational modes in nanojunctions. We present a multichannel scattering
      technique, which can be applied to calculate the transport properties for
      realistic systems, and we show how it is related to other methods that are useful
      in particular cases. We apply our technique to describe recent experiments on the
      conductance through molecular junctions.

PMID- 15956207
TI  - A quasi-Monte Carlo Metropolis algorithm.
AB  - This work presents a version of the Metropolis-Hastings algorithm using quasi
      Monte Carlo inputs. We prove that the method yields consistent estimates in some
      problems with finite state spaces and completely uniformly distributed inputs. In
      some numerical examples, the proposed method is much more accurate than ordinary
      Metropolis-Hastings sampling.

PMID- 15956205
TI  - Multiple subsets of side-chain packing in partially folded states of alpha
      lactalbumins.
AB  - Photochemically induced dynamic nuclear polarization NMR pulse-labeling
      techniques have been used to obtain detailed information about side-chain surface
      accessibilities in the partially folded (molten globule) states of bovine and
      human alpha-lactalbumin prepared under a variety of well defined conditions.
      Pulse labeling involves generating nuclear polarization in the partially folded
      state, rapidly refolding the protein within the NMR sample tube, then detecting
      the polarization in the well dispersed native-state spectrum. Differences in the
      solvent accessibility of specific side chains in the various molten globule
      states indicate that the hydrophobic clusters involved in stabilizing the alpha
      lactalbumin fold can be formed from interactions between a variety of different
      hydrophobic residues in both native and non-native environments. The multiple
      subsets of hydrophobic clusters are likely to result from the existence of
      distinct but closely related local minima on the free-energy landscape of the
      protein and show that the fold and topology of a given protein may be formed from
      degenerate groups of side chains.

PMID- 15956208
TI  - A single-molecule diode.
AB  - We have designed and synthesized a molecular rod that consists of two weakly
      coupled electronic pi -systems with mutually shifted energy levels. The asymmetry
      thus implied manifests itself in a current-voltage characteristic with pronounced
      dependence on the sign of the bias voltage, which makes the molecule a prototype
      for a molecular diode. The individual molecules were immobilized by sulfur-gold
      bonds between both electrodes of a mechanically controlled break junction, and
      their electronic transport properties have been investigated. The results indeed
      show diode-like current-voltage characteristics. In contrast to that, control
      experiments with symmetric molecular rods consisting of two identical pi-systems
      did not show significant asymmetries in the transport properties. To investigate
      the underlying transport mechanism, phenomenological arguments are combined with
      calculations based on density functional theory. The theoretical analysis
      suggests that the bias dependence of the polarizability of the molecule feeds
      back into the current leading to an asymmetric shape of the current-voltage
      characteristics, similar to the phenomena in a semiconductor diode.

PMID- 15956209
TI  - The molecular basis of ferroportin-linked hemochromatosis.
AB  - Mutations in the iron exporter ferroportin (Fpn) (IREG1, SLC40A1, and MTP1)
      result in hemochromatosis type IV, a disorder with a dominant genetic pattern of
      inheritance and heterogeneous clinical presentation. Most patients develop iron
      loading of Kupffer cells with relatively low saturation of plasma transferrin,
      but others present with high transferrin saturation and iron-loaded hepatocytes.
      We show that known human mutations introduced into mouse Fpn-GFP generate
      proteins that either are defective in cell surface localization or have a
      decreased ability to be internalized and degraded in response to hepcidin.
      Studies using co-immunoprecipitation of epitope-tagged Fpn and size-exclusion
      chromatography demonstrated that Fpn is multimeric. Both WT and mutant Fpn
      participate in the multimer, and mutant Fpn can affect the localization of WT
      Fpn, its stability, and its response to hepcidin. The behavior of mutant Fpn in
      cell culture and the ability of mutant Fpn to act as a dominant negative explain
      the dominant inheritance of the disease as well as the different patient
      phenotypes.

PMID- 15956210
TI  - Delays in Pseudomonas aeruginosa quorum-controlled gene expression are
      conditional.
AB  - Acyl-homoserine lactone (acyl-HSL) signaling is thought to mediate quorum sensing
      in many species of Proteobacteria. The opportunistic human pathogen Pseudomonas
      aeruginosa uses acyl-HSLs to regulate hundreds of genes, including many that code
      for extracellular virulence factors. The idea that the P. aeruginosa acyl-HSLs
      serve as quorum-sensing signals has been questioned recently because microarray
      experiments show that the addition of signals to cultures of P. aeruginosa does
      not advance the onset of transcription for most acyl-HSL-dependent genes. We show
      that, under specific conditions, the expression of many acyl-HSL-dependent genes
      can be triggered at low culture density by signal addition. If complex medium is
      conditioned by growth of a non-acyl-HSL-producing P. aeruginosa, signals can
      eliminate the delay in expression of a battery of acyl-HSL-dependent genes.
      Furthermore, for one representative gene, lasB, there is no delay when signals
      are added to P. aeruginosa growing in conditioned complex medium or in minimal
      medium. We conclude that complex medium contains an inhibitor or inhibitors that
      can prevent induction of many, but not all, acyl-HSL-regulated genes and that the
      inhibitor is consumed by P. aeruginosa. Our results show that acyl-HSL signals
      can trigger expression of a large number of acyl-HSL-dependent genes regardless
      of growth phase. In this way, signaling in P. aeruginosa appears similar to
      quorum signaling in other Proteobacteria.

PMID- 15956212
TI  - Recruitment of DNA methyltransferase I to DNA repair sites.
AB  - In mammalian cells, the replication of genetic and epigenetic information is
      directly coupled; however, little is known about the maintenance of epigenetic
      information in DNA repair. Using a laser microirradiation system to introduce DNA
      lesions at defined subnuclear sites, we tested whether the major DNA
      methyltransferase (Dnmt1) or one of the two de novo methyltransferases (Dnmt3a,
      Dnmt3b) are recruited to sites of DNA repair in vivo. Time lapse microscopy of
      microirradiated mammalian cells expressing GFP-tagged Dnmt1, Dnmt3a, or Dnmt3b1
      together with red fluorescent protein-tagged proliferating cell nuclear antigen
      (PCNA) revealed that Dnmt1 and PCNA accumulate at DNA damage sites as early as 1
      min after irradiation in S and non-S phase cells, whereas recruitment of Dnmt3a
      and Dnmt3b was not observed. Deletion analysis showed that Dnmt1 recruitment was
      mediated by the PCNA-binding domain. These data point to a direct role of Dnmt1
      in the restoration of epigenetic information during DNA repair.

PMID- 15956211
TI  - A cysteine-sulfinic acid in peroxiredoxin regulates H2O2-sensing by the
      antioxidant Pap1 pathway.
AB  - The Schizosaccharomyces pombe transcription factor Pap1 regulates antioxidant
      gene transcription in response to H2O2. Pap1 activation occurs only at low, but
      not elevated, H2O2 concentrations that instead strongly trigger the mitogen
      activated protein kinase Sty1 pathway. Here, we identify the peroxiredoxin Tpx1
      as the upstream activator of Pap1. We show that, at low H2O2 concentrations, this
      oxidant scavenger can transfer a redox signal to Pap1, whereas higher
      concentrations of the oxidant inhibit the Tpx1-Pap1 redox relay through the
      temporal inactivation of Tpx1 by oxidation of its catalytic cysteine to a
      sulfinic acid. This cysteine modification can be reversed by the sulfiredoxin
      Srx1, its expression in response to high doses of H2O2 strictly depending on
      active Sty1. Thus, Tpx1 oxidation to the cysteine-sulfinic acid and its reversion
      by Srx1 constitutes a previously uncharacterized redox switch in H2O2 signaling,
      restricting Pap1 activation within a narrow range of H2O2 concentrations.

PMID- 15956213
TI  - Richness of plant-insect associations in Eocene Patagonia: a legacy for South
      American biodiversity.
AB  - South America has some of the most diverse floras and insect faunas that are
      known, but its Cenozoic fossil record of insects and insect herbivory is sparse.
      We quantified insect feeding on 3,599 leaves from the speciose Laguna del Hunco
      flora (Chubut, Argentina), which dates to the early Eocene climatic optimum (52
      million years ago) and compared the results with three well preserved, rich, and
      identically analyzed early- and middle-Eocene floras from the following sites in
      North America: Republic, WA; Green River, UT; and Sourdough, WY. We found
      significantly more damage diversity at Laguna del Hunco than in the North
      American floras, whether measured on bulk collections or on individual plant
      species, for both damage morphotypes and feeding groups. An ancient history of
      rich, specialized plant-insect associations on diverse plant lineages in warm
      climates may be a major factor contributing to the current biodiversity of South
      America.

PMID- 15956214
TI  - Probing charge transport at the single-molecule level on silicon by using
      cryogenic ultra-high vacuum scanning tunneling microscopy.
AB  - A cryogenic variable-temperature ultra-high vacuum scanning tunneling microscope
      is used for measuring the electrical properties of isolated cyclopentene
      molecules adsorbed to the degenerately p-type Si(100)-2x1 surface at a
      temperature of 80 K. Current-voltage curves taken under these conditions show
      negative differential resistance at positive sample bias, in agreement with
      previous observations at room temperature. Because of the enhanced stability of
      the scanning tunneling microscope at cryogenic temperatures, repeated
      measurements can be routinely taken over the same molecule. Taking advantage of
      this improved stability, we show that current-voltage curves on isolated
      cyclopentene molecules are reproducible and possess negligible hysteresis for a
      given tip-molecule distance. On the other hand, subsequent measurements with
      variable tip position show that the negative differential resistance voltage
      increases with increasing tip-molecule distance. By using a one-dimensional
      capacitive equivalent circuit and a resonant tunneling model, this behavior can
      be quantitatively explained, thus providing insight into the electrostatic
      potential distribution across a semiconductor-molecule-vacuum-metal tunnel
      junction. This model also provides a quantitative estimate for the alignment of
      the highest occupied molecular orbital of cyclopentene with respect to the Fermi
      level of the silicon substrate, thus suggesting that this experimental approach
      can be used for performing chemical spectroscopy at the single-molecule level on
      semiconductor surfaces. Overall, these results serve as the basis for a series of
      design rules that can be applied to silicon-based molecular electronic devices.

PMID- 15956215
TI  - Arranging matter by magnetic nanoparticle assemblers.
AB  - We introduce a method for transporting colloidal particles, large molecules,
      cells, and other materials across surfaces and for assembling them into highly
      regular patterns. In this method, nonmagnetic materials are manipulated by a
      fluid dispersion of magnetic nanoparticles. Manipulation of materials is guided
      by a program of magnetic information stored in a substrate. Dynamic control over
      the motion of nonmagnetic particles can be achieved by reprogramming the
      substrate magnetization on the fly. The unexpectedly large degree of control over
      particle motion can be used to manipulate large ensembles of particles in
      parallel, potentially with local control over particle trajectory.

PMID- 15956216
TI  - WZsGreen/+: a new green fluorescent protein knock-in mouse model for the study of
      KIT-expressing cells in gut and cerebellum.
AB  - In the small intestine, interstitial cells of Cajal (ICC) surrounding the
      myenteric plexus generate the pacemaking slow waves that are essential for an
      efficient intestinal transit. The underlying molecular mechanisms of the slow
      wave are poorly known. KIT is currently the sole practical marker for ICC.
      Attempts to purify living ICC have so far largely failed, due to the loss of the
      KIT epitope during enzymatic dissociation. Aiming to identify and isolate living
      ICC, we designed a knock-in strategy to express a fluorescent tag in KIT
      expressing cells by inserting the sequence of the novel green fluorescent protein
      ZsGreen into the first exon of the c-Kit gene, creating a null allele called
      W(ZsGreen). In the gastrointestinal tract of heterozygous W(ZsGreen)/+ mice, tiny
      ZsGreen fluorescent dots were observed in all KIT-expressing ICC populations,
      with exception of ICC at the deep muscular plexus in small intestine. During
      development of the gastrointestinal tract, ZsGreen expression followed KIT
      expression in a spatiotemporal way. Stellate and basket KIT-expressing cells in
      the molecular layer of the cerebellum also exhibited ZsGreen dots, whereas no
      ZsGreen was detected in skin, testis, and bone marrow. ZsGreen dot-containing
      intestinal cells could be isolated from jejunum and maintained alive in culture
      for at least 3 days. ZsGreen is a suitable alternative to EGFP in transgenic
      animals. The novel W(ZsGreen)/+ model reported here appears to be a promising
      tool for live studies of KIT-expressing cells in the gastrointestinal tract and
      cerebellum and for the further analysis of pacemaker mechanisms.

PMID- 15956217
TI  - Association of Kir6.2 and INS VNTR variants with glucose homeostasis in young
      obese.
AB  - Although insulin secretion is commonly increased and glucose tolerance decreased
      in young obese patients, there is a wide individual variability of these
      parameters. We investigated whether common variants at the Kir6.2 (KCNJ11) and
      insulin variable number of tandem repeat (INS VNTR) loci are associated with
      insulin or glucose levels in 388 obese children. The E23K and INS VNTR alleles
      showed no significant association when each locus was examined individually but a
      clear effect when the two loci were combined for analysis. In obese children with
      Kir6.2 KK and class III VNTR alleles, fasting glucose was slightly but
      consistently greater (4.76 +/- 0.05 mM) than in those with Kir6.2 EE and class
      I/I VNTR alleles (4.63 +/- 0.06 mM, P = 6.10(-4)) or other genotypes (4.64 +/-
      0.03 mM, P = 1.10(-3)). Obese children with KK and class III VNTR genotypes also
      had an early response to oral glucose diminished by approximately 36%
      [insulinogenic index (IGI) = 50 +/- 4] compared with Kir6.2 EE and class I/I (IGI
      = 78 +/- 7, P = 0.026) or other genotypes (IGI = 69 +/- 3, P = 0.001). In young
      European obese, the polymorphisms of Kir6.2 and INS VNTR are thus associated with
      a trend for lower insulin and higher glucose levels, which may reveal a possible
      epistatic genetic effect that may influence a prediabetic trait in young obese
      children.

PMID- 15956218
TI  - Sensitivity variation of doped Fricke gel irradiated with monochromatic
      synchrotron X rays between 33.5 and 80 keV.
AB  - An experimental binary radiotherapy proposes the concomitant use of a high-Z
      compound and synchrotron X rays for enhancing radiation dose selectively in
      tumours by a photoelectric effect. This study aimed at measuring the resulting
      dose enhancement in irradiated material. A doped Fricke gel dosemeter model was
      manufactured with 10 mg ml(-1) of iodine (Telebrix) or barium (Micropaque).
      Samples were irradiated with a monochromatic synchrotron beam at 33.5, 50, 65 and
      80 keV. The ensuing enhancement of the sensitivity of the dosemeter was derived
      from the nuclear magnetic resonance relaxation rates measured at different X-ray
      doses. Our results demonstrate (1) the preservation of a linear relationship
      between relaxation rates and X-ray doses for dosemeters doped with high-Z atoms
      and (2) a clear energy-dependent sensitivity enhancement for barium-doped Fricke
      gels. This enhancement was neither reproducible with iodinated compounds nor
      clearly related to the expected dose enhancement factor. However 1% barium
      sulphate in the gel could significantly improve the gel's response when it was
      irradiated by low-energy X rays.

PMID- 15956219
TI  - Occupational exposures of Chinese medical radiation workers in 1986-2000.
AB  - Data on occupational exposures from medical uses of radiation in China during
      1986-2000 are presented. Individual dose monitoring results in the reports of
      monitoring centres in different provinces in China during 1986-2000 were
      collected as the basic data. These data were summarised and then analysed. From
      1986 to 2000, in diagnostic radiology, nuclear medicine and radiotherapy, the
      annual collective effective doses varied within the range 122.4-206.6, 5.4-9.3
      and 4.1-10.3 man Sv, respectively; the average annual effective dose in these
      categories varied within the range 1.5-2.2, 1.2-1.6 and 1.0-1.5 mSv,
      respectively. Almost all the average annual effective doses in medical uses of
      radiation were <3 mSv in 1986-2000, and no monitored workers were found to have
      received an occupational exposure >50 mSv in a single year or >100 mSv in a 5-y
      period. After 1990, the protection status of medical radiation workers in China
      was sufficient.

PMID- 15956220
TI  - Development of a radon trap device using a corona discharge.
AB  - Radon is one of the noble gases, which are chemically inert and do not make any
      reactants under normal conditions. In this experiment we demonstrated an
      enigmatic reaction between radon and fluorine when a corona discharge is used as
      a promoter. Distinctive changes in radon concentrations were caused by the
      discharge and a trap efficiency of >99.5% was estimated. The mass balance between
      the trapped and the released radon was found to be reasonable. This indicates the
      existence of chemical reactions with radon. This trap phenomenon has application
      as a technique for reducing radon concentration in radon-contaminated air. It is
      possible that this technique will be applicable to other noble gases.

PMID- 15956221
TI  - Comment: Promethazine adverse events after implementation of a medication
      shortage interchange.

PMID- 15956222
TI  - Zoledronic Acid and renal toxicity: data from French adverse effect reporting
      database.
AB  - BACKGROUND: Zoledronic acid-associated renal impairment leading to renal failure
      has been recently reported in a cohort of US patients. However, the presence of
      such toxicity in other populations has not yet been determined. OBJECTIVE: To
      analyze French cases of zoledronic acid-associated nephrotoxicity. METHODS: We
      evaluated available cases with acute deterioration of renal function associated
      with zoledronic acid therapy drawn from the French Adverse Event Reporting System
      database until July 1, 2004. RESULTS: We identified 4 men and 3 women between the
      ages of 52 and 70 years, with multiple myeloma or different types of metastatic
      cancer, who had experienced renal impairment during zoledronic acid therapy. Four
      patients developed de novo acute renal failure, while the other 3 patients
      experienced acute deterioration of preexisting chronic renal failure. Renal
      failure occurred after various durations of zoledronic acid therapy (1-120 days).
      Three patients completely recovered and one partially recovered their previous
      renal function after discontinuation of zoledronic acid, but renal impairment was
      associated with a fatal outcome in 2 cases; the outcome of the other case was
      unknown. Our data confirm the previously reported risk factors for zoledronic
      acid-associated nephrotoxicity such as advanced cancer, multiple myeloma,
      preexisting renal failure, diabetes, hypertension, and concomitant use of
      nephrotoxic drugs. CONCLUSIONS: These cases emphasize the need for regular
      monitoring of renal function during zoledronic acid treatment, with particular
      attention to patients with preexisting impaired renal function.

PMID- 15956227
TI  - Use of the transtheoretical model in the medication use process.
AB  - OBJECTIVE: To review articles published during the past 10 years relating to the
      transtheoretical model (TTM) and the medication use process, focusing on
      prescribing, dispensing, and using prescription and nonprescription medications
      for legitimate purposes. DATA SOURCES: MEDLINE, Cochrane database, PsychINFO,
      International Pharmaceutical Abstracts, and PubMed were searched from 1995 to
      August 2004 using the key terms models, psychological; prescriptions, drug;
      drugs, nonprescription; models, theoretical; self medication; patient compliance;
      medication compliance; decision making; drug therapy and behavior change.
      Additional searches included the following terms: pharmacists, community; TTM;
      transtheoretical model, pharmacy services, new practice patterns and physician
      practice patterns. STUDY SELECTION AND DATA EXTRACTION: Studies with empirical
      application of any aspect of TTM were included. Abstracts were reviewed by both
      authors, and data were independently abstracted including, for example, specific
      aspects of TTM used or tested, context for model use or setting, and results and
      authors' suggestions for future use of TTM. The reviewers came to consensus on
      all abstracted information. DATA SYNTHESIS: Eleven articles were identified that
      contained TTM and drug use; however, only 5 were empirical applications. There
      were 2 types of applications of TTM in medication use: measurement of stage of
      change regarding adherence and prediction of adherence using TTM concepts. A 1-
      and 2-item measure of adherence stage of change have been validated. Medication
      adherence stage of change varied by type of drug. The pros and cons of taking the
      medicine and stage of change were useful in predicting adherence. No intervention
      studies to improve adherence were identified. CONCLUSIONS: TTM has not been used
      extensively to examine the medication use process. Without further research, no
      clear recommendation can be provided as to the effectiveness of TTM in improving
      the drug use process, but it remains promising.

PMID- 15956228
TI  - Hemodialysis clearance of metronidazole following overdose.

PMID- 15956229
TI  - Efficacy and tolerability of levetiracetam treatment in an epileptic patient with
      SLE.

PMID- 15956230
TI  - Effect of the freezing conditions and microwave thawing power on the stability of
      cefuroxime in dextrose 5% infusion polyolefin bags at 4 degrees C.
AB  - BACKGROUND: Intravenous cefuroxime sodium solution could be prepared in advance
      by a centralized hospital pharmacy service to improve safety and time management.
      OBJECTIVE: To investigate the effect of freezing and microwave thawing on the
      solution stability of cefuroxime. METHODS: Cefuroxime 1.5 g in 100 mL of dextrose
      5% in polyolefin bags was frozen individually (group A) or in one package (group
      B) for 98 days at -20 degrees C. The solutions were then thawed using microwaves
      at 270 (light cycle) or 800 watts (hard cycle) and stored at 4 degrees C. The
      cefuroxime concentration was measured by HPLC. Visual inspection was performed
      and pH was measured at that time. Stability of the solution was defined as a
      concentration remaining superior to 90% of the initial concentration by
      regression analysis. RESULTS: No color change or precipitation in the solutions
      was observed. In group A, stability was at least 23 and 21 days after light and
      hard cycle thawing, respectively. In group B, stability was at least 21 and 18
      days, respectively, with the pH increasing without affecting chromatographic
      parameters. CONCLUSIONS: The optimal conditions for advance preparation of a
      solution containing cefuroxime 1.5% in dextrose 5% may be freezing of individual
      containers followed by a light cycle of microwave thawing.

PMID- 15956231
TI  - Once-daily abacavir in place of twice-daily administration.
AB  - OBJECTIVE: To review the safety and efficacy of a once-daily dosage regimen for
      abacavir, a nucleoside reverse transcriptase inhibitor. DATA SOURCES: English
      language MEDLINE and Iowa Drug Information Service database reports were accessed
      from 1966 to March 2005. International Pharmaceutical Abstracts was searched from
      1970 to March 2005. The key words used in all searches were abacavir and Ziagen.
      Article bibliographies were used to identify additional relevant articles. The
      Internet was searched to identify abstracts of poster and oral presentations that
      have not yet been published. The manufacturer was also contacted to obtain
      unpublished information. STUDY SELECTION AND DATA EXTRACTION: Publications were
      included that provided information related to the safety and efficacy of abacavir
      when used once daily. Preference was given to randomized, double-blind,
      controlled trials comparing once-daily abacavir regimens with other
      antiretroviral regimens. Abstracts from professional meetings were included for
      unpublished studies, and conference coverage reviews were included if the
      abstracts were not available. DATA SYNTHESIS: In trials directly comparing once-
      and twice-daily abacavir, little difference was shown in the efficacy of the 2
      regimens. Despite similar adverse effect profiles, significantly more severe
      hypersensitivity reactions and severe diarrhea were seen with once-daily abacavir
      in one trial. CONCLUSIONS: Once-daily administration of abacavir has not been
      shown to be inferior to twice-daily dosing, but it may put patients at increased
      risk for severe hypersensitivity reactions and diarrhea. More data are needed to
      confirm this risk.

PMID- 15956232
TI  - Tinzaparin in outpatients with pulmonary embolism or deep vein thrombosis.
AB  - BACKGROUND: The low-molecular-weight heparins (LMWHs) have been shown to be
      effective in the outpatient treatment of deep vein thrombosis (DVT). Data
      regarding outpatient use of any LMWH in pulmonary embolism (PE) or tinzaparin in
      DVT while transitioning therapy to a vitamin K antagonist are limited. OBJECTIVE:
      To determine the safety and efficacy of tinzaparin in patients with either DVT or
      PE being transitioned to warfarin during LMWH therapy in the outpatient setting.
      METHODS: All patients who were treated with at least one outpatient dose of
      tinzaparin for venous thromboembolism (VTE) were identified. Charts of all
      patients followed within the University of California Davis healthcare system
      were reviewed. The incidence of bleeding and recurrent thromboembolism over a
      minimum of the first 4 weeks to a maximum of 12 weeks after initiating
      anticoagulation was assessed. RESULTS: A total of 178 patients with acute VTE
      were treated with tinzaparin, and outcomes could be determined in 140 cases.
      Forty-seven percent of these patients had objectively documented PE. Only one
      (0.7%) case of recurrent VTE was observed. Major bleeding was documented in 5
      (3.6%) and minor bleeding in 8 (5.8%) patients. Two bleeding events, both major,
      occurred during tinzaparin therapy. CONCLUSIONS: Outpatient use of tinzaparin
      during transition to warfarin therapy in the treatment of VTE, including PE,
      appears to be feasible in patients who are judged candidates for home therapy.

PMID- 15956233
TI  - Acute liver failure with renal impairment related to the abuse of senna
      anthraquinone glycosides.
AB  - OBJECTIVE: To report a case of chronic ingestion of very large amounts of senna
      fruits as an herbal tea, possibly leading to severe hepatotoxicity. CASE SUMMARY:
      A 52-year-old woman who had ingested, for >3 years, one liter of an herbal tea
      each day made from a bag containing 70 g of dry senna fruits, developed acute
      hepatic failure and renal impairment requiring intensive care therapy. The
      severity of the hepatic failure was reflected by the increase in prothrombin time
      (international normalized ratio >7) and the development of encephalopathy. Liver
      transplantation was discussed, but the patient ultimately recovered with
      supportive therapy. Renal impairment was consistent with proximal tubular
      acidosis, also with marked polyuria refractory to vasopressin administration.
      Suprisingly, large amounts of cadmium were transiently recovered in the urine.
      DISCUSSION: Cassia acutifolia and angustifolia plants are widely used as
      laxatives. Their chronic abuse may be associated with serious manifestations,
      including fluid and electrolyte loss, with chronic diarrhea. Severe
      hepatotoxicity is unusual, but could be explained by the exposure of the liver to
      unusual amounts of toxic metabolites of anthraquinone glycosides (sennosides). An
      objective causality assessment suggests that hepatotoxicity was possibly related
      to senna laxative abuse. Regarding nephrotoxicity, there are no available human
      data on sennosides, while experimental models suggest that anthraquinone
      derivatives may also accumulate in the kidneys. The finding of high urinary
      concentrations of cadmium would suggest contamination of the herbal tea by
      metals, but this hypothesis could not be verified. CONCLUSIONS: Ingestion of
      large doses of senna laxatives may expose people to the risk of hepatotoxicity.

PMID- 15956234
TI  - Evidence-based practice by pharmacists: utilization and barriers.
AB  - BACKGROUND: Evidence-based medicine (EBM) is the use of the current best evidence
      from research to make practice and policy decisions. Little is known regarding
      the attitudes of pharmacists toward EBM. OBJECTIVE: To determine the attitudes of
      pharmacists toward EBM, the extent that pharmacists use evidence to make
      decisions, and identify barriers to the use of evidence. METHODS: A self
      administered questionnaire was mailed to 2000 randomly selected Illinois licensed
      pharmacists. The questionnaire assessed the pharmacists' attitudes toward EBM,
      the extent to which recommendations are based on primary and tertiary literature,
      and perceived barriers to the use of EBM. RESULTS: Completed responses were
      received from 323 pharmacists (17.2% response rate). Overall, respondents had
      positive attitudes toward EBM (58% positive, 32% somewhat positive). Respondents
      thought research findings were useful (42%) or very useful (42%) to daily
      practice. Nearly one-half (49.8%) of respondents had conducted a primary
      literature search within the past year. Hospital pharmacists and pharmacists in
      other practice settings were more likely than community pharmacists to conduct a
      literature search in the past year (75%, 61%, and 30%, respectively; p < 0.001).
      Although 86% of respondents reported having Internet access at home, only 42% of
      all respondents identified that they had PubMed access at home. Common barriers
      to the use of EBM include lack of time (45%), physician attitudes toward
      pharmacist recommendations (19%), and access to resources (11%). CONCLUSIONS:
      Pharmacist respondents have positive attitudes toward EBM and the application of
      research findings to practice.

PMID- 15956235
TI  - Relative thromboembolic risks associated with COX-2 inhibitors.
AB  - OBJECTIVE: To evaluate the clinical literature on cyclooxygenase-2 (COX-2)
      inhibitors to determine whether a greater incidence of thromboembolic events is
      universal within the drug class. DATA SOURCES: A MEDLINE search was conducted
      (1996-March 2005) for key articles in the English language assessing the efficacy
      or safety of these agents. STUDY SELECTION AND DATA EXTRACTION: Randomized,
      double-blind, and controlled trials, as well as case-control and retrospective
      cohort studies, that assessed the cardiovascular safety of COX-2 inhibitors were
      reviewed. DATA SYNTHESIS: Seventeen published studies were reviewed, and the
      cardiovascular safety data were extracted from each trial. The mechanism by which
      COX-2 inhibitors may induce a thromboembolic event is likely multifactorial
      involving (1) COX-2-specific isoform binding affinity, (2) drug dose, (3)
      duration of therapy, and (4) cardiovascular risk profile of the patient. Evidence
      supports an association between cardiovascular adverse events and the use of
      rofecoxib, valdecoxib, and celecoxib. However, this risk is not equally
      distributed among the drugs. Given the relative paucity of data, lumiracoxib and
      etoricoxib cardiovascular effects remain uncertain. CONCLUSIONS: Each COX-2
      inhibitor has a unique cardiovascular risk profile. Based on the current
      evidence, celecoxib is the safest COX-2 inhibitor when prescribed appropriately
      in the lowest possible dose for the shortest duration in the ideal target
      population.

PMID- 15956236
TI  - Possible colchicine rhabdomyolysis in a fluvastatin-treated patient.

PMID- 15956237
TI  - Effect of cyclobenzaprine on tricyclic antidepressant assays.
AB  - OBJECTIVE: To evaluate cyclobenzaprine interference on tricyclic antidepressant
      assays. DATA SOURCES: Literature was identified through a MEDLINE search (1966
      August 2004) using the search terms cyclobenzaprine, tricyclic antidepressant,
      toxicology, and assay. DATA SYNTHESIS: Cyclobenzaprine is structurally similar to
      tricyclic antidepressants and is often identified as a tricyclic antidepressant
      on toxicology assays. Older chromatographic assays demonstrate retention time
      differences of only seconds and nearly identical color stains between
      cyclobenzaprine and individual tricyclic antidepressants. In comparison,
      ultraviolet absorption ratios of 4.18 for amitriptyline and 1.85 for
      cyclobenzaprine are easily distinguished. Spectroscopy also consistently
      identifies cyclobenzaprine's unique mass-to-charge ratio peaks of 275 and 215
      compared with those of amitriptyline. Available bioanalytic techniques are
      reviewed for their ability to correctly identify cyclobenzaprine and
      differentiate the drug from tricyclic antidepressants. CONCLUSIONS: When assays
      are positive for tricyclic antidepressants without a history of their use, an
      attempt should be made to identify confounders, such as cyclobenzaprine. Newer
      bioanalytic techniques, such as ultraviolet absorption and mass spectroscopy,
      accurately identify cyclobenzaprine in such instances.

PMID- 15956238
TI  - Intentional and unintentional nonadherence to antihypertensive medication.
AB  - BACKGROUND: Hypertension is poorly controlled in the US due to medication
      nonadherence. Recent evidence suggests that nonadherence can be classified as
      intentional or unintentional and different patient characteristics, such as the
      experience of adverse effects, may be associated with each. OBJECTIVE: To examine
      associations between patient characteristics, including reported adverse effects,
      and both intentional and unintentional nonadherence among 588 hypertensive
      patients. METHODS: Baseline data from a clinical trial, the Veterans' Study To
      Improve the Control of Hypertension, were examined. Intentional and unintentional
      nonadherence were assessed using a self-report measure. Participants were
      presented with a list of adverse effects commonly associated with
      antihypertensive medication and asked to indicate which symptoms they had
      experienced. Logistic regression analyses were used to examine adjusted
      associations between patient characteristics and type of nonadherence. RESULTS:
      Approximately 31% of patients reported unintentional nonadherence and 9% reported
      intentional nonadherence. Non-white participants, individuals without diabetes
      mellitus, and individuals reporting > or = 5 adverse effects were more likely to
      report intentional nonadherence than their counterparts. Individuals with less
      than a 10th-grade education and non-white participants were more likely to report
      unintentional nonadherence than their counterparts. When symptoms of increased
      urination and wheezing/shortness of breath were reported, patients were more
      likely to report intentional and unintentional nonadherence compared with those
      who were adherent. Unintentional nonadherence was also associated with reports of
      dizziness and rapid pulse. CONCLUSIONS: Both intentional and unintentional
      nonadherence are common and related to perceived adverse effects. Furthermore,
      different interventions may be necessary to improve adherence in unintentionally
      and intentionally nonadherent patients.

PMID- 15956239
TI  - FDA policy on unapproved drug products: past, present, and future.
AB  - OBJECTIVE: To review the history of drug regulation by the Food and Drug
      Administration (FDA) as it relates to unapproved drugs and FDA policy, along with
      the FDA's efforts to avoid future incidents by amending and enforcing those
      policies that are already in place. DATA SOURCES: Data from FDA history
      documents, FDA guidances, Code of Federal Regulations Title 21, and presentations
      by the FDA's Office of Compliance were gathered. STUDY SELECTION AND DATA
      EXTRACTION: All information identified from the data sources was evaluated, and
      all information deemed relevant was included for this review. DATA SYNTHESIS:
      Contrary to popular belief, there are drugs on the market that have not been
      evaluated for safety or efficacy by the FDA. For almost a century, the FDA has
      taken action against public health threats posed by unapproved drug products, and
      today's drugs and vaccines are required to demonstrate both safety and efficacy
      prior to marketing. The FDA has taken great strides to ensure the welfare of
      Americans by reacting to disasters that have occurred in the past and being
      proactive by setting regulations that will prevent such catastrophes from
      occurring in the future. CONCLUSIONS: The FDA recognizes that drug regulation is
      an ongoing process and that, although we have come a long way, there is still
      much to be done.

PMID- 15956240
TI  - Anticoagulation monitoring part 2: Unfractionated heparin and low-molecular
      weight heparin.
AB  - OBJECTIVE: To review the availability, mechanisms, limitations, and clinical
      application of point-of-care (POC) devices used in monitoring anticoagulation
      with unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). DATA
      SOURCES: Articles were identified through a MEDLINE search (1966-August 2004),
      device manufacturer Web sites, additional references listed in articles and Web
      sites, and abstracts from scientific meetings. STUDY SELECTION AND DATA
      EXTRACTION: English-language literature from clinical trials was reviewed to
      evaluate the accuracy, reliability, and clinical application of POC monitoring
      devices. DATA SYNTHESIS: The activated partial thromboplastin time (aPTT) and
      activated clotting time (ACT) are common tests for monitoring anticoagulation
      with UFH. Multiple devices are available for POC aPTT, ACT, and heparin
      concentration testing. The aPTT therapeutic range for UFH will vary depending
      upon the reagent and instrument employed. Although recommended by the American
      College of Chest Physicians Seventh Conference on Antithrombotic and Thrombolytic
      Therapy, establishing a heparin concentration-derived therapeutic range for UFH
      is rarely performed. Additional research evaluating anti-factor Xa monitoring of
      LMWHs using POC testing is necessary. CONCLUSIONS: Multiple POC devices are
      available to monitor anticoagulation with UFH. For each test, there is some
      variability in results between devices and between reagents used in the same
      device. Despite these limitations, POC anticoagulation monitoring of UFH using
      aPTT and, more often, ACT is common in clinical practice, particularly when
      evaluating anticoagulation associated with interventional cardiology procedures
      and cardiopulmonary bypass surgery.

PMID- 15956241
TI  - A possible case of gynecomastia with fluoxetine.

PMID- 15956242
TI  - Aripiprazole prescribing and continuation rates during psychiatric
      hospitalization.

PMID- 15956243
TI  - Caspofungin and amphotericin B for disseminated Fusarium verticillioides in
      leukemia.

PMID- 15956245
TI  - Selective and irreversible cell cycle inhibition by diphenyleneiodonium.
AB  - Because cell proliferation is subject to checkpoint-mediated regulation of the
      cell cycle, pharmacophores that target cell cycle checkpoints have been used
      clinically to treat human hyperproliferative disorders. It is shown here that the
      flavoprotein inhibitor diphenyleneiodionium can block cell proliferation by
      targeting of cell cycle checkpoints. Brief exposure of mitotically arrested cells
      to diphenyleneiodonium induces a loss of the mitotic cell morphology, and this
      corresponds with a decrease in the levels of the mitotic markers MPM2 and phospho
      histone H3, as well as a loss of centrosome maturation, spindle disassembly, and
      redistribution of the chromatin remodeling helicase ATRX. Surprisingly, this
      mitotic exit resulted in a tetraploidization that persisted long after drug
      release. Analogously, brief exposure to diphenyleneiodonium also caused prolonged
      arrest in G(1) phase. By contrast, diphenyleneiodonium exposure did not abrogate
      S phase, although it did result in a subsequent block of G(2) cell cycle
      progression. This indicates that diphenyleneiodonium selectively targets
      components of the cell cycle, thereby either causing cell cycle arrest, or
      checkpoint override followed by cell cycle arrest. These irreversible effects of
      diphenyleneiodonium on the cell cycle may underlie its potent antiproliferative
      activity.

PMID- 15956244
TI  - Identification of genes and molecular pathways involved in the progression of
      premalignant oral epithelia.
AB  - An early interventional effort in oral premalignancy requires novel molecular
      targets and diagnostic biomarkers to delay or reverse incidences of malignant
      progression. Microarray-based transcriptional profiling in disease states
      provides global insight into the causal biomolecular processes and novel pathways
      involved. In this study, we investigated transcript profiles in precancerous oral
      lesions to identify nearly 1,700 genes as significantly overexpressed or
      underexpressed and a primarily affected metabolic pathway that may be responsible
      for irreversible transition to progressive stages of oral cancer. For the first
      time, we show a convergence of several genes and pathways known for their
      oncogenic capabilities, in progression of premalignant oral epithelial tissues.
      This study consequently provides a molecular basis for persistent proinflammatory
      conditions in oral premalignant tissues. We found that lipocalin-type
      prostaglandin D(2) synthase (PTGDS), a key enzyme in the arachidonic acid
      metabolism pathway, as repressed in premalignant stages. We show the protective
      role of these enzyme-derived metabolites in inhibiting cell proliferation using
      an in vitro oral cancer progression model. We have also confirmed the
      overexpression of two invasion-related biomarkers, psoriasin (PSOR1) and versican
      (CSPG2), in oral premalignant and malignant archival tissues. Our results clearly
      indicate that pharmacologic intervention with anti-inflammatory prostaglandin
      D(2)-like analogues may help prevent or delay oral epithelial carcinogenesis
      because of metabolic restoration of a negative feedback regulatory loop through
      its several cognate receptors or target molecules. Further studies directed
      toward a multitude of possible protective mechanisms of this lipocalin-type
      enzyme or its products in oral cancer progression are warranted.

PMID- 15956246
TI  - In vitro and in vivo irinotecan-induced changes in expression profiles of cell
      cycle and apoptosis-associated genes in acute myeloid leukemia cells.
AB  - OBJECTIVE: To study irinotecan (CPT-11)-induced changes in expression profiles of
      genes associated with cell cycle control and apoptosis in myeloid leukemia cells
      in vitro and in vivo. METHODS: HL60 cells were exposed to clinically achievable
      concentrations of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite
      of CPT-11, and blood sampled from patients with acute myeloid leukemia and
      chronic myeloid leukemia in myeloid blast transformation treated with CPT-11.
      Gene expression changes were studied by cDNA microarray and correlated with
      biological responses by studying DNA distributions by flow cytometry. RESULTS:
      cDNA microarray analysis showed down-regulation and up-regulation of specific
      cell cycle-associated genes, consistent with loss of S-phase cells and temporary
      delay of G(1)-S-phase transition seen by flow cytometry. Flow cytometry showed
      that cells in S phase during SN-38 exposure underwent apoptosis, whereas cells in
      G(2)-M and G(1) were delayed in G(1) and entered S phase only 6 to 8 hours after
      drug removal, consistent with the observed changes in gene expression.
      Proapoptotic changes in gene transcription included down-regulation of
      antiapoptotic genes and up-regulation of proapoptotic genes. Many gene expression
      changes observed following in vitro SN-38 exposure were also seen following in
      vivo administration of 10 or 15 mg/m(2) CPT-11; notably, proapoptotic changes
      included reduced transcription of survivin pathway-associated genes and increased
      transcription of death receptor 5. CONCLUSION: CPT-11-induced changes in gene
      expression profiles in vitro and in vivo are consistent with temporary delay in
      G(1)-S transition and enhanced responsiveness to apoptosis, both of which may
      contribute to the synergistic interactions of this drug with antimetabolites.

PMID- 15956247
TI  - Selective induction of apoptosis in mutant p53 premalignant and malignant cancer
      cells by PRIMA-1 through the c-Jun-NH2-kinase pathway.
AB  - PRIMA-1 (p53 reactivation and induction of massive apoptosis) is a chemical
      compound that was originally identified as a selective mutant p53-dependent
      growth suppressor by screening a library of low-molecular-weight compounds.
      However, its mechanism of action is unknown. In this study, we examined toxicity
      of PRIMA-1 to three premalignant human colorectal adenoma cell lines (RG/C2,
      BR/C1, and AA/C1) and four colorectal carcinoma cell lines (DLD-1, SW480, LOVO,
      and HCT116) and its mechanism of action. It selectively induced apoptosis only in
      the mutant p53 premalignant and malignant colon cell lines, but was not toxic to
      the wild-type p53 premalignant and malignant colon cell lines. Using stable
      transfectants of temperature-sensitive p53 mutant Ala(143) in null p53 H1299 lung
      cancer cells, we found that PRIMA-1 induced significantly more apoptosis in cells
      with mutant p53 conformation (37 degrees C) than the wild-type p53 conformation
      (32.5 degrees C). Cell cycle analysis indicated that its inhibition of cell
      growth was correlated with induction of G(2) arrest. Western blot analysis showed
      PRIMA-1 increased p21 and GADD45 expression selectively in the mutant p53 cells.
      However, Fas, Bcl-2 family proteins, and caspases were not involved in PRIMA-1
      induced cell death. The c-Jun-NH(2)-kinase (JNK) inhibitor SP 600125, but not p38
      mitogen-activated protein kinase inhibitor SB 203580 or extracellular signal
      regulated kinase inhibitor PD 98059, blocked PRIMA-1-induced apoptosis.
      Transfection with a dominant-negative phosphorylation mutant JNK, but not a
      dominant-negative p38 or wild-type JNK, inhibited PRIMA-1-induced cell death,
      suggesting that the JNK pathway plays an important role in PRIMA-1-induced
      apoptosis. PRIMA-1 is a highly selective small molecule toxic to p53 mutant cells
      and may serve as a prototype for the development of new p53-targeting agents for
      therapy of premalignant and malignant cells.

PMID- 15956248
TI  - ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels
      in carcinoid tumor cells.
AB  - Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that
      secrete bioactive hormones resulting in carcinoid syndrome. Few curative
      treatments exist outside of surgical resection. We have previously shown that
      activation of the Raf-1 signaling pathway can suppress hormone production in
      carcinoid tumor cells. In this study, we investigated a novel treatment for
      carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the
      compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in
      progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and
      extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372
      resulted in a significant reduction of bioactive hormone levels as well as the
      transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells.
      Furthermore, treatment with ZM336372 led to a marked suppression of cellular
      proliferation and induction of the cell cycle inhibitors p21 and p18. In summary,
      ZM336372 targets both proliferation and palliative issues associated with
      carcinoid tumor cells, and therefore, warrants further investigation as a
      possible therapeutic strategy for patients with carcinoid tumors.

PMID- 15956249
TI  - Farnesyltransferase inhibitors reverse altered growth and distribution of actin
      filaments in Tsc-deficient cells via inhibition of both rapamycin-sensitive and 
      insensitive pathways.
AB  - Farnesyltransferase inhibitors (FTI) have been developed as anticancer drugs and
      are currently being evaluated in clinical trials. In this study, we have examined
      the effects of FTIs on Tsc-null cells to gain insight into their effects on
      farnesylated Rheb GTPase. This protein is involved in the activation of mTOR/S6K
      signaling and is down-regulated by the Tsc1/Tsc2 complex. Both Tsc1(-/-) and
      Tsc2(-/-) mouse embryonic fibroblasts exhibit constitutive activation of S6K and
      grow in the absence of serum. Two different FTI compounds, the clinical compound
      BMS-214662 and the newly described BMS-225975, inhibit the constitutive
      activation of mTOR/S6K signaling and block serum-free growth of the Tsc-null
      mouse embryonic fibroblasts. We have also found that Tsc-null mouse embryonic
      fibroblasts grow under anchorage-independent conditions and that both FTI
      compounds inhibit this soft agar growth. These FTI effects are similar to those
      observed with rapamycin. Another interesting phenotype of Tsc-null mouse
      embryonic fibroblasts is that they are round and contain actin filaments
      predominantly at the cell periphery. The addition of FTIs, but not rapamycin, led
      to the reappearance of intracellular actin filaments and reduction of peripheral
      actin filaments. The ability of FTI to rearrange actin filaments seems to be
      largely mediated by the inhibition of Rheb protein, as induction of intracellular
      actin filaments by FTI was much less efficient in Tsc2-null cells expressing Rheb
      (M184L), a geranylgeranylated mutant Rheb that can bypass farnesylation. These
      results reveal that FTIs inhibit Rheb, causing two different effects in Tsc
      deficient cells, one on growth and the other on actin filament distribution.

PMID- 15956250
TI  - In vitro cytotoxicity of carcinoma cells with 111In-labeled antibodies to HER-2.
AB  - Antibodies conjugated to radionuclides emitting low-energy electrons, which
      include Auger electrons and some conversion electrons, were recently shown to
      efficiently kill cells bearing a high density of the antigen recognized. The
      primary purpose of this study was to determine if such killing could be obtained
      with anti-HER-2 antibodies conjugated to (111)In, using the chelator benzyl
      diethylenetriaminepentaacetic acid, or (125)I. Target cells were the breast
      carcinoma SK-BR-3 and the ovarian carcinoma SK-OV-3.ip1. In preliminary
      experiments, antibody accumulation and catabolism during a 2- to 3-day incubation
      with antibody was investigated. The level of antibody uptake, in terms of
      molecules per cell, was high enough such that killing seemed feasible. With an
      (125)I label, but not an (111)In label, increasing the antibody concentration
      past a certain point caused a decrease in total antibody accumulation, which
      might be attributed to effects of antibody binding. To test for cytotoxicity,
      cells were incubated for 2 days with the labeled antibody, then assayed for
      colony-forming units with a limiting dilution assay. SK-BR-3 cells were strongly
      killed ( approximately 3 logs) by antibody 21.1, and 100% kill was obtained by
      combining two noncompeting antibodies to HER-2 (21.1 and 4D5). SK-OV-3.ip.1 cells
      were more resistant to killing, but use of the two-antibody mixture produced a
      surviving fraction of approximately 0.002. (111)In-labeled antibodies to other
      high-density antigens, epithelial glycoprotein-1 and epithelial glycoprotein-2,
      also killed these target cells. In contrast, unlabeled antibodies or a
      nonreactive-labeled antibody produced much less cytotoxicity. The same experiment
      with an (131)I label (a beta-particle emitter) resulted in much greater levels of
      nonspecific cytotoxicity and essentially no specific cytotoxicity. This approach
      may be effective for therapy of micrometastases.

PMID- 15956251
TI  - Plasma vascular endothelial growth factor and interleukin-8 as biomarkers of
      antitumor efficacy of a prototypical erbB family tyrosine kinase inhibitor.
AB  - CI-1033 (N-[4-[N-(3-chloro-4-fluorophenyl)amino-7-[3-(4
      morpholynyl)propoxy]quinazolin-6-yl]acrylamide, PD 0183805-mesylate salt) was
      identified as a potent, selective inhibitor of erbB family tyrosine kinases,
      which are overexpressed in a number of solid tumors and have been shown to be
      involved in tumor progression. Because objective response of clinical patients to
      erbB-targeted therapies like CI-1033 has been observed only in a subset of cancer
      patients that exhibit the intended molecular targets, much emphasis has been
      placed on the identification of biomarkers of antitumor efficacy. Vascular
      endothelial growth factor (VEGF) and interleukin-8 (IL-8) were considered as
      potential biomarkers for CI-1033 due to ease of detection in patient plasma and
      showed roles in angiogenesis and cancer progression and positive regulation by
      the erbB receptor family. In the present studies, mice bearing established
      xenografts (A431 epidermoid carcinoma, H125 non-small cell lung carcinoma, SF767
      glioblastoma, and MDA-MB-468 mammary carcinoma) were treated with efficacious and
      subefficacious doses of CI-1033, and plasma levels and xenograft gene expression
      of VEGF and IL-8 were evaluated. Oral administration of CI-1033 to tumor-bearing
      mice at efficacious doses resulted in markedly decreased levels of VEGF and/or IL
      8 plasma levels and tumor mRNA levels relative to vehicle-treated control mice in
      xenograft models that exhibited evaluable levels of these markers. In contrast,
      subefficacious doses of CI-1033 did not significantly affect VEGF or IL-8 levels
      in any of the xenograft models. These studies indicate that plasma VEGF and IL-8
      may have use as biomarkers of antitumor efficacy for epidermal growth factor
      receptor/erbB-targeted therapies such as CI-1033 and suggest that further
      clinical study of these markers in cancer patients are warranted.

PMID- 15956252
TI  - A phase I clinical trial of a ribozyme-based angiogenesis inhibitor targeting
      vascular endothelial growth factor receptor-1 for patients with refractory solid
      tumors.
AB  - PURPOSE: This study intended to determine the maximum tolerated dose, safety,
      pharmacokinetic variables, clinical response, and pharmacodynamic markers of
      daily s.c. administration of Angiozyme. PATIENTS AND METHODS: Patients with
      refractory solid tumors were enrolled in a dose escalation and expanded cohort
      design. Dose escalation involved cohorts of patients at doses of 10, 30, 100, or
      300 mg/m(2)/d for 29 days. A second component enrolled 15 additional patients at
      a daily dose of 100 mg/m(2). Patients were eligible to continue on therapy until
      disease progression. RESULTS: Thirty-one patients were enrolled and 28 were
      evaluable (range, 29-505 days; median, 89.5 days). A maximum tolerated dose was
      not defined by toxicity but rather by the maximal deliverable dose of 300
      mg/m(2)/d. Grade 1 to 2 injection site reactions were the most common toxicities.
      One patient in the 300 mg/m(2) group experienced a reversible grade 3 injection
      site reaction. Angiozyme showed dose-dependent plasma concentrations with good
      bioavailability. Surrogate markers showed Angiozyme localization in tumor
      biopsies and a significant increase in serum von Willebrand factor antigen, a
      marker for endothelial cell dysfunction. Although Angiozyme-reactive antibody
      production was noted for some patients, no antibody-related adverse events were
      noted. Seven of 28 (25%) evaluable patients had stable disease for >or =6 months,
      with the longest treatment duration of > or =16 months. Two patients
      (nasopharyngeal carcinoma and melanoma) showed minor responses. CONCLUSION:
      Angiozyme was well tolerated with satisfactory pharmacokinetic variables for
      daily s.c. dosing. Results have provided the basis for subsequent clinical trials
      of this first-of-class biologically targeted therapeutic.

PMID- 15956253
TI  - Enhanced inhibition of murine tumor and human breast tumor xenografts using
      targeted delivery of an antibody-endostatin fusion protein.
AB  - Endostatin can inhibit angiogenesis and tumor growth in mice. A potential
      limitation of endostatin as an antitumor agent in humans is the short serum half
      life of the protein that may decrease effective concentration at the site of
      tumor and necessitate frequent dosing. In an effort to improve antitumor
      activity, endostatin was fused to an antibody specific for the tumor-selective
      HER2 antigen to create an antibody-endostatin fusion protein (anti-HER2 IgG3
      endostatin). Normal endostatin rapidly cleared from serum in mice (T(1/2)(2), =
      0.6-3.8 hours), whereas anti-HER2 IgG3-endostatin had a prolonged half-life (90%
      intact; T(1/2)(2), 40.2-44.0 hours). Antigen-specific targeting of anti-HER2 IgG3
      endostatin was evaluated in BALB/c mice implanted with CT26 tumors or CT26 tumors
      engineered to express the HER2 antigen (CT26-HER2). Radio-iodinated anti-HER2
      IgG3-endostatin preferentially localized to CT26-HER2 tumors relative to CT26
      tumors. Administration of anti-HER2 IgG3-endostatin to mice showed preferential
      inhibition of CT26-HER2 tumor growth compared with CT26. Anti-HER2 IgG3
      endostatin also markedly inhibited the growth of human breast cancer SK-BR-3
      xenografts in severe combined immunodeficient mice. Anti-HER2 IgG3-endostatin
      inhibited tumor growth significantly more effectively than endostatin, anti-HER2
      IgG3 antibody, or the combination of antibody and endostatin. CT26-HER2 tumors
      treated with the endostatin fusion protein had decreased blood vessel density and
      branching compared with untreated CT26-HER2 or CT26 treated with the fusion
      protein. The enhanced effectiveness of anti-HER2 IgG3-endostatin may be due to a
      longer half-life, improved serum stability, and selective targeting of endostatin
      to tumors, resulting in decreased angiogenesis. Linking of an antiangiogenic
      protein, such as endostatin, to a targeting antibody represents a promising and
      versatile approach to antitumor therapy.

PMID- 15956254
TI  - Sapphyrins induce apoptosis in hematopoietic tumor-derived cell lines and show in
      vivo antitumor activity.
AB  - Sapphyrins are pentapyrrolic, metal-free, expanded porphyrins. In the present
      study, the activity of sapphyrins as anticancer agents in hematopoietic-derived
      tumor cells was explored. It was found that a dihydroxylated water-soluble
      sapphyrin derivative (PCI-2000) is a potent inducer of apoptosis in a wide
      variety of tumor cell lines including lymphoma (Ramos, DHL-4, and HF-1), leukemia
      (Jurkat and HL-60), and myeloma (8226/S, 1-310, C2E3, and 1-414). PCI-2000
      triggers an apoptotic pathway in these tumor cells as shown by release of
      cytochrome c from mitochondria; activation of caspases 9, 8, and 3; cleavage of
      the caspase substrate poly(ADP-ribose) polymerase; and Annexin V binding.
      Apoptosis can be partially inhibited by overexpression of the antiapoptotic
      protein Bcl-2 or treatment with benzyloxycarbonyl-valine-alanine-aspartic acid
      fluoromethylketone, a cell-permeable caspase inhibitor. Both PCI-2000 and PCI
      2010, a tetrahydroxy bis-carbamate derivative of PCI-2000, result in increased
      levels of phosphorylated p38 mitogen-activated protein kinase. Inhibition of p38
      mitogen-activated protein kinase phosphorylation resulted in a synergistic
      increase of PCI-2000 cytotoxicity. PCI-2010 showed less toxicity in mice than PCI
      2000 and was active in slowing the growth of Ramos and HL-60 tumor xenografts in
      nude mice. These results provide preclinical rationale for the further study of
      sapphyrins for potential use in the treatment of hematopoietic-derived tumors.

PMID- 15956256
TI  - A highly epothilone B-resistant A549 cell line with mutations in tubulin that
      confer drug dependence.
AB  - A 95-fold epothilone B (EpoB)-resistant, but not dependent, A549 human lung
      carcinoma cell line, A549.EpoB40 (EpoB40), has a Gln to Glu mutation at residue
      292 that is situated near the M-loop of betaI-tubulin. Further selection of this
      cell line with higher concentrations of EpoB produced A549.EpoB480 (EpoB480),
      which is approximately 900-fold resistant to EpoB. This cell line, like EpoB40,
      exhibits cross-resistance to Taxol and extreme sensitivity to vinblastine, but in
      contrast to EpoB40 it is unusually dependent on EpoB, requiring a minimum of 125
      nmol/L EpoB to maintain normal growth. Sequence analysis of the beta-tubulin and
      Kalpha1-tubulin genes in EpoB480 showed that, in addition to the beta292
      mutation, beta60 was mutated from Val to Phe and alpha195 was mutated from Leu to
      Met. Mass spectrometry indicated that both the Val(60)Phe and Leu(195)Met
      mutations in betaI- and Kalpha1-tubulin, respectively, were expressed at the
      protein level. Molecular modeling indicated that beta60 is located at the end of
      the H1-S2 loop that has been implicated as a principal partner of the M-loop for
      contacts between protofilaments. A mutation at beta60 could inhibit the lateral
      contacts between protofilaments, thereby destabilizing microtubules. alpha195 is
      located at the external surface of the microtubule that has been proposed as the
      domain that interacts with a variety of endogenous proteins, such as stathmin and
      microtubule-associated protein 4. A mutation at alpha195 could modulate the
      interactions between tubulin and regulatory proteins. We propose that the
      betaVal(60)Phe mutation plays a critical role in the drug-dependent phenotype of
      EpoB480 cells.

PMID- 15956255
TI  - Potent and selective inhibitors of Akt kinases slow the progress of tumors in
      vivo.
AB  - The Akt kinases are central nodes in signal transduction pathways that are
      important for cellular transformation and tumor progression. We report the
      development of a series of potent and selective indazole-pyridine based Akt
      inhibitors. These compounds, exemplified by A-443654 (K(i) = 160 pmol/L versus
      Akt1), inhibit Akt-dependent signal transduction in cells and in vivo in a dose
      responsive manner. In vivo, the Akt inhibitors slow the progression of tumors
      when used as monotherapy or in combination with paclitaxel or rapamycin. Tumor
      growth inhibition was observed during the dosing interval, and the tumors regrew
      when compound administration was ceased. The therapeutic window for these
      compounds is narrow. Efficacy is achieved at doses approximately 2-fold lower
      than the maximally tolerated doses. Consistent with data from knockout animals,
      the Akt inhibitors induce an increase in insulin secretion. They also induce a
      reactive increase in Akt phosphorylation. Other toxicities observed, including
      malaise and weight loss, are consistent with abnormalities in glucose metabolism.
      These data show that direct Akt inhibition may be useful in cancer therapy, but
      significant metabolic toxicities are likely dose limiting.

PMID- 15956257
TI  - Transfection of melanoma cells with antisense PAX3 oligonucleotides additively
      complements cisplatin-induced cytotoxicity.
AB  - Advanced melanoma is difficult to treat, in part because of greater resistance to
      therapy compared with other cancer types. The mechanisms underlying this
      resistance are not well-understood. One factor that is reported to be involved in
      melanoma cell survival is PAX3, a transcription factor normally expressed during
      embryonic development, and which is critically required for development of neural
      crest-derivatives, including skin melanocytes. PAX3 expression is deregulated in
      primary melanomas and most melanoma cell lines. Here we have investigated whether
      targeting PAX3 expression in melanoma cell lines together with chemotherapeutic
      treatment increases susceptibility to therapeutic cell death. Using PAX3-specific
      antisense oligodeoxynucleotides (PAX3-AS) to treat melanoma cell lines in vitro,
      we showed dose-dependent reduction of proliferation of melanoma cells, and
      induction of apoptosis compared with control treatments. Induction of apoptosis
      was accompanied by the induction of active caspase-3 in UACC62 and M14 cells, and
      p53 protein in UACC62 cells. Treatment of melanoma cells with cisplatin induces
      DNA damage and cytotoxicity, which is thought to be via p53-dependent and 
      independent mechanisms. Treatment of either p53 mutant (M14) or wild-type
      (UACC62) melanoma cells with cisplatin, and varying doses of PAX3-AS, resulted in
      percentages of cells undergoing apoptosis equivalent to the sum of the individual
      treatments, irrespective of mutation status [e.g., UACC62, 43.8% (1 micromol/L
      PAX3-AS), 30.1% (20 micromol/L cisplatin), 69.6% (PAX3-AS + cisplatin); M14,
      12.6% (1 micromol/L PAX3-AS), 41.5% (40 micromol/L cisplatin), 50.2% (PAX3-AS +
      cisplatin)]. These data suggest that treatment of melanoma cells with PAX3-AS
      complements cytotoxicity induced by cisplatin.

PMID- 15956258
TI  - The sesquiterpene lactone parthenolide in combination with docetaxel reduces
      metastasis and improves survival in a xenograft model of breast cancer.
AB  - Parthenolide, a sesquiterpene lactone, shows antitumor activity in vitro, which
      correlates with its ability to inhibit the DNA binding of the antiapoptotic
      transcription factor nuclear factor kappaB (NF-kappaB) and activation of the c
      Jun NH(2)-terminal kinase. In this study, we investigated the chemosensitizing
      activity of parthenolide in vitro as well as in MDA-MB-231 cell-derived xenograft
      metastasis model of breast cancer. HBL-100 and MDA-MB-231 cells were used to
      measure the antitumor and chemosensitizing activity of parthenolide in vitro.
      Parthenolide was effective either alone or in combination with docetaxel in
      reducing colony formation, inducing apoptosis and reducing the expression of
      prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1 in vitro. In an
      adjuvant setting, animals treated with parthenolide and docetaxel combination
      showed significantly enhanced survival compared with untreated animals or animals
      treated with either drug. The enhanced survival in the combination arm was
      associated with reduced lung metastases. In addition, nuclear NF-kappaB levels
      were lower in residual tumors and lung metastasis of animals treated with
      parthenolide, docetaxel, or both. In the established orthotopic model, there was
      a trend toward slower growth in the parthenolide-treated animals but no
      statistically significant findings were seen. These results for the first time
      reveal the significant in vivo chemosensitizing properties of parthenolide in the
      metastatic breast cancer setting and support the contention that metastases are
      very reliant on activation of NF-kappaB.

PMID- 15956259
TI  - Conditionally replicative adenovirus expressing degradation-resistant p53 for
      enhanced oncolysis of human cancer cells overexpressing murine double minute 2.
AB  - Conditionally replicative adenoviruses (CRAd) are under investigation as
      anticancer agents. Previously, we found that the CRAd AdDelta24-p53, expressing
      the p53 tumor suppressor protein from its genome, more effectively killed most
      human cancer cells than did its parent AdDelta24. However, a minority of cancer
      cell lines poorly responded to the oncolysis-enhancing effect of p53. Here we
      show that refractory cell lines expressed high levels of the major negative p53
      regulator murine double minute 2 (MDM2). To obviate MDM2-mediated inactivation of
      CRAd-encoded p53, we constructed the new CRAd AdDelta24-p53(14/19) encoding a p53
      variant incapable of binding to MDM2. AdDelta24-p53(14/19) was approximately 10
      times more effective than AdDelta24-p53 in killing cancer cell lines with high
      levels of human MDM2, but not cells with low MDM2. This finding supports the
      notion that exogenous expression of functional p53 augments the anticancer
      efficacy of CRAds. In addition, it confirms that high MDM2 expression is a
      molecular determinant of resistance against oncolysis enhancement by exogenous
      wild-type p53. Moreover, it shows that efficacy enhancement by restoration of
      functional p53 can also be accomplished in cancer cells expressing a p53
      inhibitor. This further expands the utility of CRAds expressing functional p53
      variants for effective virotherapy of cancer and thus their possible contribution
      to the advancement of individualized molecular medicine.

PMID- 15956260
TI  - p53 alpha-Helix mimetics antagonize p53/MDM2 interaction and activate p53.
AB  - Overexpression or hyperactivation of MDM2 contributes to functional inactivation
      of wild-type p53 in nearly 50% of tumors. Inhibition of p53 by MDM2 depends on
      binding between an NH(2)-terminal (residues 16-28) p53 alpha-helical peptide and
      a hydrophobic pocket on MDM2, presenting an attractive target for development of
      inhibitors against tumors expressing wild-type p53. Here we report that novel p53
      alpha-helical peptide mimics based on a terphenyl scaffold can inhibit MDM2-p53
      binding in vitro and activate p53 in vivo. Several active compounds have been
      identified that inhibit MDM2-p53 binding in an ELISA assay with IC(50) of 10 to
      20 micromol/L and induce p53 accumulation and activation in cell culture at 15 to
      40 micromol/L. These results suggest that p53 alpha-helical mimetics based on the
      terphenyl scaffold may be developed into potent p53 activators.

PMID- 15956261
TI  - Identification of compounds that inhibit growth of 2-amino-1-methyl-6
      phenylimidazo(4,5-b)pyridine-resistant cancer cells.
AB  - The dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is
      a heterocyclic amine and is a common byproduct of cooked meat and fish. Although
      most cells undergo apoptosis when exposed to this mutagen, subsets develop
      resistance. Rather than die, these resistant cells persist and accumulate
      mutations, thereby driving tumorigenesis of exposed organs within the
      gastrointestinal tract. By applying a high-throughput cell-based screen of 32,000
      small molecules, we have identified a family of compounds that specifically
      inhibit the growth of PhIP-resistant cancer cells. These compounds may prove
      useful for the treatment or prevention of gastrointestinal tumors arising after
      exposure to PhIP and related carcinogens.

PMID- 15956263
TI  - Rates of clinical depression diagnosis, functional impairment, and nursing home
      placement in coexisting dementia and depression.
AB  - OBJECTIVE: Depression is commonly found as a coexisting condition in dementia. An
      earlier retrospective study by the authors found that patients with coexisting
      dementia and depression (CDD) were high utilizers of inpatient and nursing home
      care. The current prospective study was designed to investigate specific factors
      that might contribute to outcomes such as nursing home placement by examining the
      detection and course of CDD subjects as compared with subjects with either
      disorder alone. METHODS: Eighty-two subjects (N=29 with CDD, N=27 with Depression
      Alone, and N=26 with Dementia Alone) were recruited and reassessed at 3, 6, and
      12 months after baseline assessment. RESULTS: Lower rates of depression detection
      by treating (non-study) physicians were found in CDD subjects. Only 35% of the
      CDD group were correctly diagnosed and receiving adequate treatment for their
      depression. Although the CDD group did not differ in baseline dementia stage or
      cognitive functioning as compared with the dementia-only group, they had
      significantly higher levels of functional impairment. CDD subjects used nursing
      home care at significantly higher rates; nursing home placement correlated
      significantly with baseline severity of functional impairment and mood measures,
      but not with other factors, including dementia stage and medical burden.
      CONCLUSIONS: Undetected, untreated, or inadequately treated depression may result
      in higher rates of nursing home placement in patients with dementia by increasing
      their functional disability. Aggressive outpatient treatment of depression could
      improve the course of coexisting dementia and depression.

PMID- 15956264
TI  - Relationship of neuropsychological performance to functional status in nursing
      home residents and community-dwelling older adults.
AB  - OBJECTIVES: The authors examined the association between neuropsychological tests
      of executive functioning and episodic memory and functional disability in nursing
      home residents versus community-dwelling older adults. METHODS: The
      neuropsychological performance of 96 residents from the Jewish Home and Hospital,
      Bronx, NY and 192 gender- and age-matched older adults from residential
      communities in the New York metropolitan area was assessed in eight tasks (Word
      List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency,
      Trailmaking A and B, and Digit Symbol Substitution). Functional status was
      derived from the Clinical Dementia Rating scale (CDR) extended activities of
      daily living scores. Regression analyses were performed to test for differences
      in cross-sectional age-gradients for cognitive and functional status between
      nursing home residents and community-dwellers. Furthermore, regression analyses,
      controlling for age, gender, dementia status, and education, were performed to
      determine the association between neuropsychological performance and functional
      status, comparing domains of executive functioning and memory. RESULTS: Community
      dwelling older adults showed age-related deficits both in overall cognitive
      status and functional disability, which were larger in nursing home residents.
      Executive functioning was associated with functional disability beyond the
      effects of age, gender, education, dementia status, residential status, overall
      cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning
      is associated with functional deficits in both community-dwelling older adults
      and nursing home residents. Measures of executive functioning may prove useful in
      intervention studies aimed at delaying institutionalization.

PMID- 15956265
TI  - A cross-sectional study of neuropsychiatric symptoms in 435 patients with
      Alzheimer's disease.
AB  - OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD)
      are associated with significant patient and caregiver distress and increased
      likelihood of institutionalization. We attempted to characterize in detail these
      symptoms and the distress they cause to caregivers. METHODS: Patients with
      probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional
      Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver
      Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited.
      Neuropsychiatric symptoms of all types were highly prevalent. The most common and
      most persistent symptom was apathy (75%). Delusional symptoms were the least
      persistent. Depressive and apathetic symptoms were the earliest to appear, and
      hallucinations, elation/euphoria, and aberrant motor behavior were the latest
      symptoms to emerge. Hallucinations were significantly more common in severe
      dementia. Symptoms of irritability were most prevalent in early disease. Total
      Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST
      score. Caregivers rated their own emotional distress levels as moderate or severe
      for 10 out of 12 symptom domains. The sum total of caregiver distress was
      strongly correlated with total NPI-D but not cognition or functional state.
      Distress levels did not vary when analyzed according to the patients' place of
      residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are
      common in AD and represent a major source of distress among caregivers. The
      extent of neuropsychiatric symptomatology is seen to correlate with the level of
      functional and cognitive disability although some symptoms are variably
      persistent and related to disease stage.

PMID- 15956266
TI  - Neuropsychiatric symptoms and quality of life in Alzheimer disease.
AB  - OBJECTIVE: Authors examined the impact of neuropsychiatric symptoms in Alzheimer
      disease (AD) patients' and caregivers' quality of life (QOL) and assessed the
      relationship of caregiver distress to neuropsychiatric symptoms and caregiver
      QOL. METHODS: Sixty-two patients with probable or possible AD and their
      caregivers participated. Neuropsychiatric symptoms of patients were assessed with
      the Neuropsychiatric Inventory (NPI). QOL of both patients and caregivers was
      assessed using the QOL-Alzheimer's Disease (QOL-AD) scale. Each patient and
      caregiver completed patient QOL ratings; caregivers also completed caregiver QOL
      assessments. RESULTS: Caregiver QOL-AD was negatively correlated with
      agitation/aggression, anxiety, disinhibition, irritability/lability, and total
      NPI score. Patient QOL on both patient and caregiver ratings was negatively
      correlated with depression. Patient-reported QOL-AD ratings at different levels
      of cognitive functioning were not correlated with caregiver-reported ratings. The
      lack of relationship between patient and caregiver assessments of patient QOL was
      evident in both mildly and moderately affected patients. Caregiver QOL was
      negatively correlated with distress related to agitation/aggression,
      disinhibition, irritability/lability, and total NPI distress. CONCLUSION:
      Neuropsychiatric symptoms of AD patients adversely affect both patient and
      caregiver QOL. These results suggest that identifying and treating
      neuropsychiatric symptoms in AD may improve both patient and caregiver QOL.

PMID- 15956267
TI  - Functioning and health service use among elderly nursing home residents with
      alcohol use disorders: findings from the National Nursing Home Survey.
AB  - OBJECTIVE: The author asked whether older nursing home residents with alcohol use
      disorders differ from demographically-matched residents without alcohol use
      disorders on functioning, admission characteristics, and health services use.
      METHOD: National Nursing Home Survey data were used to compare nursing home
      residents with alcohol use disorders (N=216) with demographically-matched
      residents without alcohol use disorders (N=216) on functioning, admission
      characteristics, and health services use. RESULTS: Residents with alcohol use
      disorders functioned somewhat better than did residents in the demographically
      matched sample group, as indicated by performance of basic activities of daily
      living. However, they were significantly more likely to have lived alone before
      admission and to have obtained mental health and social services. There was a
      significant group x gender interaction on length of stay: men with alcohol use
      disorders had shorter lengths of stay than did men without alcohol use disorders;
      women with alcohol use disorders had longer lengths of stay than did women
      without such disorders. CONCLUSIONS: Having fewer social resources may contribute
      to elevated admission risk and need for mental health and social services among
      older nursing home residents who have alcohol use disorders. Duration and
      severity of alcohol problems may help explain gender differences in length of
      stay among these residents.

PMID- 15956268
TI  - How do patients with Alzheimer disease rate their overall quality of life?
AB  - OBJECTIVE: The authors asked how Alzheimer disease (AD) patients assess their
      overall quality of life (QOL) and sought to determine the characteristics
      associated with this assessment. METHODS: The authors performed a cross-sectional
      survey of 193 persons with mild-to-severe-stage AD in a University Memory
      Disorders Clinic using a single-item self-assessment of overall QOL. RESULTS: The
      181 of 193 patients (94%) able to complete a single-item QOL self-rating had less
      severe dementia than patients not able to complete, but some had Mini-Mental
      State Exam scores as low as 0. Most patients rated their QOL as "good" (35%) or
      "very good" (36%). Latino patients, patients with less education, and depressed
      patients were more likely to rate their QOL lower. Among patients able to
      estimate how they thought their family caregiver would rate their QOL (N=173;
      90%), there was moderate agreement between this estimate and their self-ratings.
      CONCLUSION: A single-item global rating of patient QOL could prove useful in
      assessing QOL of most mild-to-severe-stage AD patients. Affective impairment,
      more than cognitive or functional impairment, drives this assessment. Screening
      for and addressing depressive symptoms could improve AD patients' QOL. Despite
      impairments in insight, patients see a difference in how their caregivers would
      rate their QOL.

PMID- 15956269
TI  - Treatment of late-life depression complicated by alcohol dependence.
AB  - OBJECTIVES: Among elderly patients, mental and physical illness are often present
      along with alcohol dependence. The interaction between alcohol use and concurrent
      physical or mental disabilities is complex and complicates treatment planning.
      The aim of this study was to test the efficacy of naltrexone combined with
      sertraline for the treatment of older adults with major depression and alcohol
      dependence. METHODS: The sample was 74 subjects, age 55 and older, who met
      criteria for a depressive disorder along with alcohol dependence. All subjects
      were randomly assigned to 12 weeks of naltrexone 50 mg/day or placebo. Also, all
      subjects received sertraline 100 mg/day and individual weekly psychosocial
      support. Treatment response for alcohol consumption and depression was measured
      during the 12 weeks of treatment. RESULTS: At baseline, the average age of
      subjects was 63.4, and subjects were drinking an average of 10.7 drinks per
      drinking day. The overall results are encouraging; 42% of the subjects had a
      remission of their depression and had no drinking relapses during the trial.
      There was no evidence for an added benefit of naltrexone in combination with
      sertraline, but there was significant correlation between any alcohol relapse
      during the trial and poor response to depression treatment. CONCLUSION: Patients
      with concurrent mental disorders, such as major depression and alcohol
      dependence, are increasingly prevalent in clinical practice and have been
      demonstrated to show poorer treatment response and higher treatment costs. The
      results of this trial underscore the importance of addressing alcohol use in the
      context of treating late-life depression.

PMID- 15956270
TI  - Factors associated with falls among older, cognitively impaired people in
      geriatric care settings: a population-based study.
AB  - OBJECTIVE: The authors studied factors associated with falls among cognitively
      impaired older people in geriatric care settings. METHOD: This was a study using
      all geriatric care settings in a county in northern Sweden. Residents were
      assessed by means of the Multi-Dimensional Dementia Assessment Scale,
      supplemented with questions concerning the use of physical restraints, pain,
      previous falls during the stay, and falls and injuries during the preceding week.
      Data about both falls and cognition were collected in 3,323 residents age 65 and
      older. Of these residents 2,008 (60.4%) were cognitively impaired, and they
      became the study population. Of the participants, 69% were women; mean age: 83.5
      years. RESULTS: Of 2,008 cognitively impaired residents, 189 (9.4%) had fallen at
      least once during the preceding week. Being able to get up from a chair, previous
      falls, needing a helper when walking, and hyperactive symptoms were the factors
      most strongly associated with falls. CONCLUSION: Preventing falls in cognitively
      impaired older people is particularly difficult. An intervention strategy would
      probably have to include treatment of psychiatric and behavioral symptoms,
      improvement of gait and balance, and adjustment of drug treatment, as well as
      careful staff supervision.

PMID- 15956271
TI  - Health and psychosocial correlates of disordered gambling in older adults.
AB  - OBJECTIVE: A number of regional prevalence studies suggest that disordered
      gambling is a clinically significant problem among older adults. However, little
      research has evaluated whether older adults with a gambling disorder experience
      increased health, psychiatric, substance use, and social problems as compared
      with older adults without a gambling disorder. METHODS: A group of 48 older-adult
      disordered gamblers and 48 older adult non/infrequent gamblers, matched by age,
      sex, race, and recruitment site, completed the Addiction Severity Index (ASI),
      Brief Symptom Inventory (BSI), and Short Form-36 Health Survey (SF-36).
      Multivariate general-linear models evaluated between-group differences on these
      indices. RESULTS: Compared with non/infrequent gamblers, disordered gamblers
      reported increased severity of medical, family/social, psychiatric, and alcohol
      problems on the ASI. They also scored higher on depression, anxiety, paranoid
      ideation, and psychoticism subscales of the BSI, and lower on vitality, physical
      functioning, role-physical, general health, and social functioning subscales of
      the SF-36. CONCLUSIONS: These results suggest that older adults with a gambling
      disorder experience increased severity of health and psychosocial problems,
      compared with older adult non/infrequent gamblers matched by age, sex, race, and
      recruitment site.

PMID- 15956272
TI  - Symptoms of late-life depression: frequency and change during treatment.
AB  - OBJECTIVE: The authors determined the symptoms frequently present in older
      patients with major depression that showed the greatest change during treatment
      and that best correlated with an independent measure of improvement (the Clinical
      Global Impression scale [CGI]). METHODS: Subjects included 728 patients over the
      age of 60 years with major depression who were selected for entry into a clinical
      trial. Authors determined the frequency of symptoms on the 17-item Hamilton
      Rating Scale for Depression (Ham-D) and the effect size of symptom change during
      treatment. RESULTS: Nine symptoms were identified that were frequent, showed the
      greatest change during treatment, and best correlated with CGI. The items
      included depressed mood; loss of interest in work and activities; psychic
      anxiety; somatic symptoms, general (decreased energy); somatic anxiety; guilt;
      middle insomnia; late insomnia; and suicidal ideation. These nine items accounted
      for 92% of the variance in the 17-item Ham-D score, correlated with the CGI at a
      level similar to the 17-item Ham-D, and were at least as sensitive as the 17-item
      Ham-D for detecting drug-placebo differences. A comparison with five other
      similar approaches in non-geriatric samples suggested that the symptoms
      identified were relatively similar in both age-groups. CONCLUSIONS: Symptoms
      frequent in patients with late-life depression are similar to those in mixed-aged
      samples. Nine of the Ham-D items appear most useful for assessment of change
      during treatment.

PMID- 15956273
TI  - Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc
      analysis of pooled data from three large trials.
AB  - OBJECTIVE: The authors explored the effect of galantamine on behavioral symptoms
      in Alzheimer disease (AD). METHODS: Data were pooled from 2,033 subjects with
      mild-to-moderate AD who had participated in one of three randomized, double
      blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects
      included in this post hoc analysis had received treatment with either placebo
      (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg.
      Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory
      (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations;
      2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition,
      elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant
      motor behavior. RESULTS: At endpoint, mean changes from baseline in NPI scores
      were significantly different between galantamine-treated subjects and placebo
      treated subjects, favoring galantamine for several measures: total NPI,
      individual domains of agitation/aggression, anxiety, disinhibition, and aberrant
      motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was
      small. CONCLUSIONS: In this pooled sample of more than 2,000 subjects with mild
      to-moderate AD, those who received galantamine therapy experienced modestly
      better, but statistically significant, outcomes in their behavioral symptoms than
      placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and
      aberrant motor behaviors may represent a specific group of cholinergic-responsive
      behavioral symptoms.

PMID- 15956274
TI  - Serum anticholinergic activity and cognition in patients with moderate-to-severe
      dementia.
AB  - OBJECTIVE: The authors investigated the association between serum anticholinergic
      activity (SAA) and cognitive performance in a group of patients with moderate-to
      severe dementia. METHODS: SAA and cognitive performance were assessed in 26
      patients admitted to a geropsychiatric unit for the treatment of behavioral
      disturbances associated with dementia. SAA was measured by radioreceptor
      competitive binding assay. Cognition was tested with the Mini-Mental State Exam
      and the Severe Impairment Battery. RESULTS: Higher SAA was associated with lower
      cognitive performance. CONCLUSION: This study extends to patients with moderate
      to-severe dementia the finding that higher SAA is associated with lower cognitive
      performance.

PMID- 15956275
TI  - Screaming and physical aggression in nursing homes.

PMID- 15956276
TI  - Human peptidoglycan recognition protein S is an effector of neutrophil-mediated
      innate immunity.
AB  - Innate immune responses to bacteria require cooperative interactions between host
      recognition molecules and phagocytes. The peptidoglycan recognition proteins
      (PGRPs) are a large group of proteins found in insects and mammals that bind to
      bacterial peptidoglycan (PGN). PGRP-S is located with other antimicrobial
      proteins, such as lysozyme, in the granules of human neutrophils. Whereas both
      PGRP-S and lysozyme recognize PGN, the exact binding specificity of human PGRP-S,
      its functional activity, and its potential synergy with other neutrophil-derived
      bactericidal proteins such as lysozyme have not been determined. Here we show
      that human PGRP-S binds to and inhibits the growth of Staphylococcus aureus
      (containing lysine-type PGN) and Escherichia coli (containing mesodiaminopimelic
      acid-type PGN). The binding affinity and thus antimicrobial activity of PGRP-S is
      determined by the third amino acid in the PGN stem peptide. Furthermore, the
      antimicrobial effect of PGRP-S against E coli is synergistic with lysozyme, and
      lysozyme and PGRP-S colocalize in neutrophil extracellular traps (NETs),
      suggesting that these granule-derived proteins act together to kill bacteria
      trapped in the NETs. Taken together, these results indicate that human PGRP-S
      plays a role in innate immunity in the context of neutrophils by contributing to
      the killing of intracellular and extracellular bacteria.

PMID- 15956278
TI  - Patients with paroxysmal nocturnal hemoglobinuria have a high frequency of
      peripheral-blood T cells expressing activating isoforms of inhibiting superfamily
      receptors.
AB  - Patients with paroxysmal nocturnal hemoglobinuria (PNH) have a large clonal
      population of blood cells deriving from hematopoietic stem cells (HSCs) deficient
      in glycosylphosphatidylinositol (GPI)-anchored surface molecules. A current model
      postulates that PNH arises through negative selection against normal HSCs exerted
      by autoreactive T cells, whereas PNH HSCs escape damage. We have investigated the
      inhibitory receptor superfamily (IRS) system in 13 patients with PNH. We found a
      slight increase in the proportion of T cells expressing IRS. In contrast to what
      applies to healthy donors, the engagement of IRS molecules on T cells from
      patients with PNH elicited a powerful cytolytic activity in a redirected killing
      assay, indicating that these IRSs belong to the activating type. This was
      confirmed by clonal analysis: 50% of IRS+ T-cell clones in patients with PNH were
      of the activating type, while only 5% were of the activating type in healthy
      donors. Moreover, the ligation of IRS induces (1) production of tumor necrosis
      factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) and (2) brisk cytolytic
      activity against cells bearing appropriate IRS counter-ligands. In addition,
      these IRS+ T cells show natural killer (NK)-like cytolytic activity to which GPI-
      cells were less sensitive than GPI+ cells. Thus, T cells with NK-like features,
      expressing the activating isoforms of IRS, may include effector cells involved in
      the pathogenesis of PNH.

PMID- 15956279
TI  - Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic
      leukemia.
AB  - Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements
      of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment
      outcome. Therefore, novel therapeutic strategies are needed to improve prognosis.
      Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL).
      Here we demonstrate FLT3 expression in infants with MLL (n = 41) to be
      significantly higher compared to both infant (n = 8; P < .001) and noninfant
      patients with ALL (n = 23; P = .001) carrying germline MLL genes. Furthermore,
      leukemic cells from infants with MLL were significantly more sensitive to the Fms
      like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than
      noninfant ALL cells, and at least as sensitive as internal tandem duplication
      positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred
      in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However,
      measuring FLT3 phosphorylation in infants with MLL expressing varying levels of
      wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand
      independent FLT3 activation. This suggests that infant MLL cells displaying
      activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors
      such as PKC412. However, at concentrations of PKC412 minimally required to fully
      inhibit FLT3 phosphorylation, the cytotoxic effects were only fractional. Thus,
      PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of
      FLT3 inhibition alone but may involve inhibition of multiple other kinases by
      this drug.

PMID- 15956280
TI  - Dual targeting of transformed and untransformed HTLV-1-infected T cells by DHMEQ,
      a potent and selective inhibitor of NF-kappaB, as a strategy for chemoprevention
      and therapy of adult T-cell leukemia.
AB  - Human T-cell leukemia virus type I (HTLV-1) causes adult T-cell leukemia (ATL), a
      fatal T-cell leukemia resistant to chemotherapy, after more than 50 years of
      clinical latency from transmission through breast-feeding. Polyclonal expansion
      of virus-infected T cells predisposes them to transformation. Constitutive
      activation of nuclear factor-kappaB (NF-kappaB) in the leukemic cells is
      essential for their growth and survival. Blocking NF-kappaB has been shown to be
      a potential strategy to treat ATL. We tested this approach using a novel NF
      kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), and also examined its
      application to chemoprevention by selective purging of the HTLV-1-infected cells.
      DHMEQ inhibited NF-kappaB activation in primary ATL cells and cell lines derived
      from them and induced apoptotic cell death. NF-kappaB inhibition down-regulated
      expression of genes involved in antiapoptosis or cell-cycle progression. DHMEQ
      protected severe combined immunodeficiency (SCID) mice inoculated with HTLV-1
      transformed cells from death. In addition, DHMEQ selectively targeted HTLV-1
      infected cells in the peripheral blood of virus carriers in vitro, resulting in a
      decreased number of infected cells. We conclude that NF-kappaB is a potential
      molecular target for treatment and prevention of ATL. As a potent NF-kappaB
      inhibitor, DHMEQ is a promising compound allowing the translation of this
      strategy into clinical medicine.

PMID- 15956281
TI  - Altered body iron distribution and microcytosis in mice deficient in iron
      regulatory protein 2 (IRP2).
AB  - Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from
      late-onset neurodegeneration by an unknown mechanism. We report that young adult
      Irp2-/- mice display signs of iron mismanagement within the central iron
      recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with
      altered body iron distribution and compromised hematopoiesis. In comparison with
      wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum
      hemoglobin levels and hematocrit. Serum iron and transferrin saturation are
      unchanged, and hence microcytosis is not due to an overt decrease in systemic
      iron availability. The liver and duodenum are iron loaded, while the spleen is
      iron deficient, associated with a reduced expression of the iron exporter
      ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone
      marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic
      defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against
      degradation. This study links a classic regulator of cellular iron metabolism to
      systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this
      work uncovers aspects of mammalian iron metabolism that can or cannot be
      compensated for by the expression of IRP1.

PMID- 15956282
TI  - Tumor necrosis factor-alpha as trigger of platelet activation in patients with
      heart failure.
AB  - The clinical history of patients with heart failure (HF) is complicated by
      arterial thromboembolism. Platelet activation is reported in this population, but
      the underlying mechanism has not been clarified. Forty-two patients with HF
      scored according to New York Heart Association (NYHA) classification had higher
      levels of collagen-induced platelet aggregation, platelet tumor necrosis factor
      alpha (TNF-alpha) receptor expression, and serum thromboxane B2 and higher
      circulating levels of TNF-alpha than 20 healthy subjects. Coincubation of
      platelets from HF patients with an inhibitor of TNF-alpha receptors significantly
      reduced collagen-induced platelet aggregation. In vitro study demonstrated that
      TNF-alpha amplified the platelet response to collagen; this effect was inhibited
      by TNF-alpha receptor antagonist and inhibitors of arachidonic acid metabolism.
      This study showed that TNF-alpha behaves as a trigger of platelet activation
      through stimulation of the arachidonic acid pathway.

PMID- 15956284
TI  - In vitro sensitivity to imatinib-induced inhibition of ABL kinase activity is
      predictive of molecular response in patients with de novo CML.
AB  - Most patients with de novo chronic myeloid leukemia (CML) achieve good responses
      to imatinib, but the rate and degree of molecular response is variable. We
      assessed the inhibitory concentration 50% for imatinib (IC50imatinib) in 62
      patients with de novo chronic-phase CML as a predictor of molecular response.
      IC50imatinib was determined in pretherapy blood samples by measuring the in vitro
      imatinib-induced reduction of the phosphorylated form of the adaptor protein Crkl
      (CT10 regulator of kinase like). There was marked variability between patients,
      with IC50imatinib ranging from 0.375 to 1.8 microM (median, 0.6 microM). Patients
      with low IC50imatinib (IC50 < or = 0.6 microM; n = 36) had a 36% probability of
      achieving 2-log reduction in BCR-ABL (breakpoint cluster region-abelson) by 3
      months compared with 8% in patients with high IC50imatinib (n = 26) (P = .01).
      The IC50imatinib was also predictive of molecular response at 12 months, with 47%
      of patients in the low IC50imatinib group achieving 3-log reduction and 23% in
      the high IC50imatinib group (P = .03). The predictive power of IC50imatinib was
      particularly strong in patients with low Sokal scores. These data provide strong
      evidence that intrinsic sensitivity to imatinib is variable in previously
      untreated patients with CML, and the actual level of BCR-ABL kinase inhibition
      achieved is critical to imatinib response. The IC50imatinib potentially provides
      a new prognostic indicator for molecular response in patients treated with
      imatinib.

PMID- 15956283
TI  - Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for
      reactive oxygen production.
AB  - Dectin-1 is a lectin receptor for beta-glucan that is important for innate
      macrophage recognition of fungi and contributes to phagocytosis, reactive oxygen
      production, and induction of inflammatory cytokines. The mechanisms by which
      Dectin-1 mediates intracellular signaling are just beginning to be defined.
      Spleen tyrosine kinase (Syk) is a protein tyrosine kinase that is critical for
      adaptive immune responses where it mediates signaling through B-cell receptors, T
      cell receptors, and Fc receptors. Here we report that Dectin-1 activates Syk in
      macrophages and is important for Dectin-1-stimulated reactive oxygen production,
      but not for phagocytosis. Syk activation is restricted to a subpopulation of
      macrophages that is in equilibrium with cells that cannot activate the pathway.
      The proportion of macrophages using this signaling pathway can be modulated by
      cytokine treatment. Thus, Dectin-1 signaling reveals dynamic macrophage
      heterogeneity in inflammatory activation potential.

PMID- 15956285
TI  - Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a
      potent suppressor of dendritic-cell maturation and trafficking.
AB  - Triptolide (TPT) is a chemically defined, potent immunosuppressive compound
      isolated from an anti-inflammatory Chinese herbal medicine. TPT has been reported
      to inhibit autoimmunity, allograft rejection, and graft-versus-host disease
      (GVHD), and its efficacy was previously attributed to the suppression of T cells.
      Since dendritic cells (DCs) play a major role in the initiation of T-cell
      mediated immunity, we studied the effects of TPT on the phenotype, function, and
      migration of human monocyte-derived DCs. TPT treatment, over a pharmacologic
      concentration range, inhibited the lipopolysaccharide (LPS)-induced phenotypic
      changes, characteristic of mature DCs and the production of interleukin-12p70 (IL
      12p70). Consequently, the allostimulatory functions of DCs were impaired by TPT
      treatment. Furthermore, the calcium mobilization and chemotactic responses of LPS
      stimulated DCs to secondary lymphoid tissue chemokine (SLC)/CC chemokine ligand
      21 (CCL21) were significantly lower in TPT-treated than untreated DCs, in
      association with lower chemokine receptor 7 (CCR7) and higher CCR5 expression.
      Egress of Langerhans cells (LCs) from explanted mouse skin in response to
      macrophage inflammatory protein-3beta (MIP-3beta)/CCL19 was arrested by TPT. In
      vivo administration of TPT markedly inhibited hapten (fluorescein isothiocyanate
      [FITC])-stimulated migration of mouse skin LCs to the draining lymph nodes. These
      data provide new insight into the mechanism of action of TPT and indicate that
      the inhibition of maturation and trafficking of DCs by TPT contributes to its
      immunosuppressive effects.

PMID- 15956286
TI  - The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease
      in men by modulating platelet function and structure.
AB  - The discoid form of platelets is maintained by a marginal band of tightly coiled
      microtubules. beta1-tubulin is the major isoform within platelet and
      megakaryocyte microtubules. In 24.2% of 33 unrelated inherited
      macrothrombocytopenia patients and in 10.6% of 272 subjects of a healthy
      population a P for Q substitution in beta1-tubulin was found in the highly
      conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced
      platelet protein beta1-tubulin expression. Transfection of green fluorescent
      protein (GFP)-tagged Q43P beta1-tubulin in megakaryocytic MEG01 cells resulted in
      a disturbed tubulin organization. Electron microscopy revealed enlarged
      spherocytic platelets with a disturbed marginal band and organelle-free zones. In
      addition, platelets with the Q43P beta1-tubulin variant had reduced adenosine
      triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced
      aggregation and collagen adhesion. The prevalence of the Q43P beta1-tubulin
      variant was also 2 times higher (odds ratio, [OR] = 2.1;95% confidence interval
      [CI], 1.22-3.59) among control subjects than among patients with cardiovascular
      disease (10.4% versus 5.2%, P < .001). By analyzing this protective factor in men
      and women separately, this association was only found in men. This study thus
      presents the functional consequences of the platelet Q43P beta1-tubulin
      substitution that is frequent in the healthy population and may protect men
      against arterial thrombosis.

PMID- 15956287
TI  - Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in
      vivo: role of P-selectin.
AB  - The presence of activated platelets and platelet-leukocyte aggregates in the
      circulation accompanies major surgical procedures and occurs in several chronic
      diseases. Recent findings that activated platelets contribute to the inflammatory
      disease atherosclerosis made us address the question whether activated platelets
      stimulate normal healthy endothelium. Infusion of activated platelets into young
      mice led to the formation of transient platelet-leukocyte aggregates and resulted
      in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after
      infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of
      activated P-selectin-/- platelets did not induce leukocyte rolling, indicating
      that platelet P-selectin was involved in the endothelial activation. The
      endothelial activation did not require platelet CD40L. Leukocyte rolling was
      mediated solely by the interaction of endothelial P-selectin and leukocyte P
      selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with
      von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade
      bodies on infusion of activated platelets was indicated by both elevation of
      plasma VWF levels and by an increase in the in vivo staining of endothelial P
      selectin. We conclude that the presence of activated platelets in circulation
      promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and
      P-selectin-mediated leukocyte rolling.

PMID- 15956288
TI  - Thrombus formation induced by antibodies to beta2-glycoprotein I is complement
      dependent and requires a priming factor.
AB  - We monitored the number of intravascular platelet-leukocyte aggregates (PLAs) and
      thrombotic occlusions (TOs) by intravascular microscopy in the mesentery of rats
      receiving antiphospholipid (aPL) immunoglobulin G (IgG) purified from the sera of
      patients with antiphospholipid syndrome. aPL IgG had no procoagulant effect, but
      it caused rapid endothelial deposition of fibrinogen, followed by PLA and TO in
      rats receiving an intraperitoneal injection of bacterial lipopolysaccharide 3
      hours before IgG infusion. Anti-beta2-glycoprotein I-depleted aPL IgG failed to
      induce PLAs and TOs. C3 and C9 colocalized with aPL IgG on the mesenteric
      vessels. The number of PLAs and TOs was markedly reduced in C6-deficient rats and
      in animals treated with anti-C5 miniantibody, suggesting the contribution of the
      terminal complement (C) complex to the aPL antibody-mediated intravascular
      thrombosis. In conclusion, our data indicate that antibodies to beta2
      glycoprotein I trigger coagulation subsequent to a priming proinflammatory factor
      and that the terminal C complex is the main mediator of the coagulation process.

PMID- 15956289
TI  - Absence of inducible costimulator on alloreactive T cells reduces graft versus
      host disease and induces Th2 deviation.
AB  - Inducible costimulator (ICOS) is expressed on activated and memory T cells and is
      involved in the regulation of cytokine production. We studied the role of ICOS on
      alloreactive T cells in graft versus host disease (GVHD) and determined that ICOS
      expression was up-regulated on alloreactive T cells in recipients of an
      allogeneic hematopoietic stem cell transplantation (allo-HSCT) with GVHD. We
      compared ICOS-/- T cells with wild-type (WT) T cells in 2 GVHD models. In both
      models, recipients of ICOS-/- T cells demonstrated significantly less GVHD
      morbidity and mortality, which was associated with less intestinal and hepatic
      GVHD but increased cutaneous GVHD. In addition, recipients of ICOS-/- donor T
      cells displayed a slight decrease in graft versus leukemia (GVL) activity.
      Further analysis of alloreactive ICOS-/- T cells showed no defect in activation,
      proliferation, cytotoxicity, and target organ infiltration. Recipients of ICOS-/-
      T cells had decreased serum levels of interferon-gamma (IFN-gamma), while
      interleukin-4 (IL-4) and IL-10 levels were increased, suggesting that
      alloreactive ICOS-/- T cells are skewed toward T helper-2 (Th2) differentiation.
      These data suggest a novel role for ICOS in the regulation of Th1/Th2 development
      of activated T cells. In conclusion, alloreactive ICOS-/- donor T cells induce
      less GVHD due to a Th2 immune deviation while GVL activity is slightly
      diminished.

PMID- 15956291
TI  - Invited review: Bovine milk fat globule membrane as a potential nutraceutical.
AB  - For the last 15 yr, a great deal of knowledge has been accumulated on health
      beneficial factors, protein and nonprotein, of bovine milk fat globule membrane
      (MFGM). Among the health-beneficial components of the MFGM are cholesterolemia
      lowering factor, inhibitors of cancer cell growth, vitamin binders, inhibitor of
      Helicobacter pylori, inhibitor of beta-glucuronidase of the intestinal
      Escherichia coli, xanthine oxidase as a bactericidal agent, butyrophilin as a
      possible suppressor of multiple sclerosis, and phospholipids as agents against
      colon cancer, gastrointestinal pathogens, Alzheimer's disease, depression, and
      stress. All of the above compel us to consider bovine MFGM as a potential
      nutraceutical.

PMID- 15956290
TI  - Extraembryonic expression of EPCR is essential for embryonic viability.
AB  - The endothelial cell protein C receptor (EPCR) augments protein C activation by
      the thrombin-thrombomodulin complex. Deletion of the EPCR gene (Procr) in mice
      leads to embryonic lethality before embryonic day 10 (E10.0). EPCR is detected in
      the giant trophoblast cells at the feto-maternal boundary from E7.5 and weakly in
      embryonic aortic endothelial cells from E13.5, suggesting that extraembryonic
      EPCR expression may be essential for embryonic viability. Using conditional knock
      out strategies, we demonstrate that Procr-deficient embryos with EPCR expression
      on placenta giant trophoblasts can be carried to term and then develop normally.
      Conversely, EPCR expression in the embryo, without expression in the giant
      trophoblast cells, does not rescue the mice. In genetically modified mice with
      low tissue factor activity, Procr deficiency is not lethal to the embryo. As
      adults, Procr-deficient mice generate more thrombin and activate less protein C
      in response to procoagulant stimuli. Spontaneous thrombin formation in the
      deficient animals increases with age. These findings show that extraembryonic
      EPCR expression is critical for embryo development.

PMID- 15956292
TI  - Bioavailability of vitamin D from fortified process cheese and effects on vitamin
      D status in the elderly.
AB  - We conducted 2 studies to determine the effect of vitamin D-fortified cheese on
      vitamin D status and the bioavailability of vitamin D in cheese. The first study
      was designed to determine the effect of 2 mo of daily consumption of vitamin D3
      fortified (600 IU/d) process cheese on serum 25-hydroxyvitamin D (25-OHD),
      parathyroid hormone (PTH), and osteocalcin (OC) concentrations among 100 older (>
      or =60 yr) men and women. Participants were randomized to receive vitamin D
      fortified cheese, nonfortified cheese, or no cheese. Serum levels of 25-OHD, PTH,
      and OC were measured at the beginning and end of the study. There were no
      differences in 25-OHD, PTH, or OC after 2 mo of fortified cheese intake. The
      vitamin D-fortified cheese group had a greater decrease in 25-OHD than other
      groups, due to higher baseline 25-OHD. A second study was conducted to determine
      whether the bioavailability of vitamin D2 in cheese (delivering 5880 IU of
      vitamin D2/56.7-g serving) and water (delivering 32,750 IU/250 mL) is similar and
      whether absorption differs between younger and older adults. The second study was
      a crossover trial involving 2 groups of 4 participants each (younger and older
      group) that received single acute feedings of either vitamin D2-fortified cheese
      or water. Serial blood measurements were taken over 24 h following the acute
      feeding. Peak serum vitamin D and area under the curve were similar between
      younger (23 to 50 yr) and older (72 to 84 yr) adults, and vitamin D2 was absorbed
      more efficiently from cheese than from water. These studies demonstrated that
      vitamin D in fortified process cheese is bioavailable, and that young and older
      adults have similar absorption. Among older individuals, consuming 600 IU of
      vitamin D3 daily from cheese for 2 mo was insufficient to increase serum 25-OHD
      during limited sunlight exposure.

PMID- 15956293
TI  - Enhanced lactose cheese milk does not guarantee calcium lactate crystals in
      finished cheddar cheese.
AB  - Three experimental batches of Cheddar cheese were manufactured in duplicate, with
      standardization of the initial cheese-milk lactose content to high (5.24%),
      normal (4.72%, control), and low lactose (3.81%). After 35 d of aging at 4.4
      degrees C, the cheeses were subjected to temperature abuse (24 h at 21 degrees C,
      unopened) and contamination (24 h at 21 degrees C, packages opened and cheeses
      contaminated with crystal-containing cheese). After aging for 167 d, residual
      cheese lactose (0.08 to 0.43%) and L(+)-lactate concentrations (1.37 to 1.60%)
      were high and D(-)-lactate concentrations were low (<0.03%) for all cheeses. No
      significant differences in lactose concentrations were attributable to
      temperature abuse or contamination. No significant differences in L(+)- or D(-)
      lactate concentrations were attributable to temperature abuse. However,
      concentrations of L(+)-lactate were significantly lower and D(-)-lactate were
      significantly higher in contaminated cheeses than in control cheeses, indicating
      inoculation (at d 35) with heterofermentative nonstarter lactic acid bacteria
      able to racemize L(+)-lactate to D(-)-lactate. The fact that none of the cheeses
      exhibited crystals after 167 d demonstrates that high cheese milk or residual
      lactose concentrations do not guarantee crystal formation. Contamination with
      nonstarter lactic acid bacteria can significantly contribute to D(-)-lactate
      accumulation in cheese.

PMID- 15956294
TI  - Astringency of bovine milk whey protein.
AB  - Whey protein solutions at pH 3.5 elicited an astringent taste sensation. The
      astringency of whey protein isolate (WPI), the process whey protein (PWP) that
      was prepared by heating WPI at pH 7.0, and the process whey protein prepared at
      pH 3.5 (aPWP) were adjusted to pH 3.5 and evaluated by 2 sensory analyses (the
      threshold method and the scalar scoring method) and an instrumental analysis
      (taste sensor method). The taste-stimulating effects of bovine and porcine
      gelatin were also evaluated. The threshold value of astringency of WPI, PWP, and
      aPWP was 1.5, 1.0, and 0.7 mg/mL, respectively, whereas the gelatins did not give
      definite astringency. It was confirmed by the scalar scoring method that the
      astringency of these proteins increased with the increase in protein
      concentration, and these proteins elicited strong astringency at 10 mg/mL under
      acidic conditions. On the other hand, the astringency was not elicited at pH 3.5
      by 2 types of gelatin. A taste sensor gave specific values for whey proteins at
      pH 3.5, which corresponded well to those obtained by the sensory analysis.
      Elicitation of astringency induced by whey protein under acidic conditions would
      be caused by aggregation and precipitation of protein molecules in the mouth.

PMID- 15956295
TI  - Contributions of terminal peptides to the associative behavior of alphas1-casein.
AB  - The N- and C-terminal segments of bovine alphas1-casein-B (f1-23 and f136-196)
      were characterized under conditions that promoted or inhibited self-association
      to determine the relative contributions of each fragment to the interaction of
      alphas1-casein with itself or with other caseins. In earlier studies of f1-23,
      nuclear magnetic resonance (NMR) data and circular dichroism (CD) spectra showed
      that its conformation was thermostable between 10 degrees and 25 degrees C. In
      contrast, NMR studies of f136-196 indicated temperature sensitivity between 10
      and 60 degrees C, as did near-UV and far-UV CD data, suggesting a molten globule
      like structure at higher temperatures. To compare the effects of temperature on
      conformational attributes of alphas1-casein and its terminal peptides, additional
      CD studies were conducted over a broader temperature range (10 to 70 degrees C).
      The far-UV CD spectra indicated little temperature sensitivity for alphas1
      casein, and the N-terminal peptide remained thermostable. During molecular
      dynamics simulations, the N-terminal peptide conformation did not change
      significantly, but the conformation of the C-terminal peptide (f136-196) was
      dramatically altered. These changes are correlated with the thermal instability
      observed by both CD and NMR in f136-196. Analytical ultracentrifugation studies
      of the self-association reactions of genetic variants A, B, and C of alphas1
      casein showed that at 37 degrees C the associative state is primarily dimeric;
      the amounts of higher order polymers significantly decreased when temperature was
      increased from 20 to 37 degrees C. In all 3 genetic variants, the C-terminal
      portion of the whole molecule showed thermal instability with respect to
      aggregation to higher polymers, confirming the predictions of CD data and
      molecular dynamics simulations. The temperature dependency of these
      conformational changes suggests a possible function for alphas1-casein in
      facilitating casein-casein interactions in casein micelle formation.

PMID- 15956296
TI  - Composition, microstructure, and surface barrier layer development during brine
      salting.
AB  - The goal of this study was to characterize the changes in chemical composition,
      porosity, and structure that occur at the surface of a block of brine-salted
      cheese and their relationship to the rate at which salt is taken up from the
      brine. To create a difference in composition, salt uptake, and barrier layer
      properties, identical blocks of Ragusano cheese were placed in saturated and 18%
      salt brine at 18 degrees C for 12 d. The overall moisture content and porosity
      decreased, whereas salt and salt in moisture content increased near the surface
      of blocks of brine-salted Ragusano cheese for all treatments. The general
      appearance of the microstructure of the surface of the blocks of brine-salted
      cheese was much more compact than the microstructure 1 mm inside the block at
      both brine concentrations. Large differences in porosity of the barrier layer
      were produced by brine-salting cheese in 18% vs. saturated brine, with cheese in
      saturated brine having much lower porosity at the surface and taking up much less
      salt during brining. The macro network of water channels within the
      microstructure of the cheese was less open near the surface of the block for
      cheese in both saturated and 18% brine after 4 d. However, no large differences
      in the size of the macro channels in the cheese structure due to the difference
      in brine concentration were observed by scanning electron microscopy. It is
      possible that the shrinkage of the much smaller pore structure within the casein
      matrix of the cheese is more important and will become more limiting to the rate
      of salt diffusion. Further microstructure work at higher resolution is needed to
      answer this question. The calculated decrease in porosity at the exterior 1-mm
      portion of the block was 50.8 and 29.2% for cheeses that had been in saturated
      vs. 18% brine for 12 d, respectively. The difference in brine concentration had a
      very large impact on the salt in moisture content of the cheese. The exterior of
      the cheese in 18% brine reached a salt in moisture content almost identical to
      that of the brine very quickly (17.3% at 4 d), whereas the salt in moisture
      content at the surface of the cheese block in saturated brine was only 11.9% at 4
      d. There appears to be some critical concentration of salt in brine above which
      there is a large negative impact on salt uptake due to the creation of a barrier
      layer at the surface of the block of cheese.

PMID- 15956297
TI  - Use of an alpha-galactosidase gene as a food-grade selection marker for
      Streptococcus thermophilus.
AB  - The alpha-galactosidase gene (aga) of Lactococcus raffinolactis ATCC 43920 was
      previously shown to be an efficient food-grade selection marker in Lactococcus
      lactis and Pediococcus acidilactici but not in Streptococcus thermophilus. In
      this study, we demonstrated that the alpha-galactosidase of L. raffinolactis is
      thermolabile and inoperative at 42 degrees C, the optimal growth temperature of
      S. thermophilus. An in vitro assay indicated that the activity of this alpha
      galactosidase at 42 degrees C was only 3% of that at 30 degrees C, whereas the
      enzyme retained 23% of its activity at 37 degrees C. Transformation of Strep.
      thermophilus RD733 with the shuttle-vector pNZ123 bearing the aga gene of L.
      raffinolactis (pRAF301) generated transformants that were stable and able to grow
      on melibiose and raffinose at 37 degrees C or below. The transformed cells
      possessed 6-fold more alpha-galactosidase activity after growth on melibiose than
      cells grown on lactose. Slot-blot analyses of aga mRNA indicated that repression
      by lactose occurred at the transcriptional level. The presence of pRAF301 did not
      interfere with the lactic acid production when the transformed cells of Strep.
      thermophilus were grown at the optimal temperature in milk. Using the recombinant
      plasmid pRAF301, which carries a chloramphenicol resistance gene in addition to
      aga, we showed that both markers were equally efficient at differentiating
      transformed from nontransformed cells. The aga gene of L. raffinolactis can be
      used as a highly efficient selection marker in Strep. thermophilus.

PMID- 15956298
TI  - Antibacterial activities of peptides from the water-soluble extracts of Italian
      cheese varieties.
AB  - Water-soluble extracts of 9 Italian cheese varieties that differed mainly for
      type of cheese milk, starter, technology, and time of ripening were fractionated
      by reversed-phase fast protein liquid chromatography, and the antimicrobial
      activity of each fraction was first assayed toward Lactobacillus sakei A15 by
      well-diffusion assay. Active fractions were further analyzed by HPLC coupled to
      electrospray ionization-ion trap mass spectrometry, and peptide sequences were
      identified by comparison with a proteomic database. Parmigiano Reggiano, Fossa,
      and Gorgonzola water-soluble extracts did not show antibacterial peptides.
      Fractions of Pecorino Romano, Canestrato Pugliese, Crescenza, and Caprino del
      Piemonte contained a mixture of peptides with a high degree of homology. Pasta
      filata cheeses (Caciocavallo and Mozzarella) also had antibacterial peptides.
      Peptides showed high levels of homology with N-terminal, C-terminal, or whole
      fragments of well known antimicrobial or multifunctional peptides reported in the
      literature: alphaS1-casokinin (e.g., sheep alphaS1-casein (CN) f22-30 of Pecorino
      Romano and cow alphaS1-CN f24-33 of Canestrato Pugliese); isracidin (e.g., sheep
      alphaS1-CN f10-21 of Pecorino Romano); kappacin and casoplatelin (e.g., cow kappa
      CN f106-115 of Canestrato Pugliese and Crescenza); and beta-casomorphin-11 (e.g.,
      goat beta-CN f60-68 of Caprino del Piemonte). As shown by the broth microdilution
      technique, most of the water-soluble fractions had a large spectrum of inhibition
      (minimal inhibitory concentration of 20 to 200 microg/mL) toward gram-positive
      and gram-negative bacterial species, including potentially pathogenic bacteria of
      clinical interest. Cheeses manufactured from different types of cheese milk (cow,
      sheep, and goat) have the potential to generate similar peptides with
      antimicrobial activity.

PMID- 15956300
TI  - Short communication: Effect of feed barrier design on the behavior of loose
      housed lactating dairy cows.
AB  - The objective of this study was to evaluate the effects of 2 feed barrier systems
      on feeding and social behavior of dairy cows. Forty-eight lactating Holstein cows
      were subjected to each of 2 treatments in a cross-over design. The treatments
      were 2 types of feed-line barriers: 1) post-and-rail, and 2) headlock. Time-lapse
      video was used to quantify the feeding behavior and incidence of aggressive
      displacements of the cows at the feed bunk. Average daily feeding time did not
      differ when cows used the headlock barrier compared with the post-and-rail
      barrier. However, there were certain changes in feeding time during periods of
      peak feeding activity: cows that had lower feeding times relative to group mates
      when using the post-and-rail barrier showed more similar feeding times to group
      mates when using the headlock barrier. There were 21% fewer displacements at the
      feed bunk when cows accessed feed by the headlock barrier compared with the post
      and-rail barrier. These results suggest that using a headlock barrier reduces
      aggression at the feed bunk and improves access to feed for socially subordinate
      cows during peak feeding periods.

PMID- 15956299
TI  - Effect of carprofen treatment following experimentally induced Escherichia coli
      mastitis in primiparous cows.
AB  - Acute Escherichia coli mastitis is one of the major sources of economic loss in
      the dairy industry due to reduced milk production, treatment costs, discarded
      milk, and occasional fatal disease. Nonsteroidal anti-inflammatory drugs (NSAIDs)
      are frequently used as adjunctive therapy to antibiotics. The objective of the
      current study was to evaluate the effect of carprofen treatment following
      infusion of Escherichia coli into the mammary glands of primiparous cows during
      the periparturient period. Severity of mastitis was scored based on the average
      milk production in the uninfected quarters on d +2 postinoculation and a clinical
      severity score. Carprofen was administered intravenously at 9 h postchallenge,
      when clinical signs of mastitis appeared. In previous work, efficacy of NSAIDs
      was mainly evaluated using clinical symptoms. In the present study, the effect of
      carprofen on innate immune response was also assessed by quantification of
      inflammatory mediators. All primiparous cows reacted as moderate responders
      throughout the experimental period. Primiparous cows were intramammarily
      inoculated with 1 x 10(4) cfu of E. coli P4:O32 in 2 left quarters. Analysis of
      blood and milk parameters, including IL-8, complement component C5a,
      lipopolysaccharide-binding protein (LBP), soluble CD14, prostaglandin E2, and
      thromboxane B2 was performed from d 0 to d +6 relative to intramammary
      inoculation. Rectal temperature in carprofen-treated animals was lower than in
      control animals at 3 and 6 h posttreatment. Treatment also restored the decreased
      reticulorumen motility that occurs during E. coli mastitis to preinfection levels
      faster than in control animals. Carprofen treatment resulted in an earlier
      normalization of the clinical severity score. Eicosanoid (prostaglandin E2 and
      thromboxane B2) production in milk tended to be inhibited by carprofen. No
      significant differences in the kinetic patterns of somatic cell count, IL-8,
      complement component C5a, LBP, and soluble CD14 were observed. In conclusion,
      carprofen treatment improved general clinical condition by effective antipyrexia
      and restoration of reticulorumen motility but did not significantly inhibit
      eicosanoid production. Carprofen treatment did not result in a significant
      decrease of chemotactic inflammatory mediators, IL-8 and C5a, and early innate
      immune molecules, sCD14 and LBP. Therefore, major modulatory effects from NSAID
      administration were not observed in this mastitis model, although a larger study
      might confirm some apparent trends obtained in the present results.

PMID- 15956301
TI  - Freestall maintenance: effects on lying behavior of dairy cattle.
AB  - In a series of 3 experiments, we documented how sand-bedding depth and
      distribution changed within freestalls after new bedding was added and the effect
      of these changes on lying behavior. In experiment 1, we measured changes in
      bedding depth over a 10-d period at 43 points in 24 freestalls. Change in depth
      of sand was the greatest the day after new sand was added and decreased over
      time. Over time, the stall surface became concave, and the deepest part of the
      stall was at the center. Based on the results of experiment 1, we measured
      changes in lying behavior when groups of cows had access to freestalls with sand
      bedding that was 0, 3.5, 5.2, or 6.2 cm at the deepest point, below the curb,
      while other dimensions remained fixed. We found that daily lying time was 1.15 h
      shorter in stalls with the lowest levels of bedding compared with stalls filled
      with bedding. Indeed, for every 1-cm decrease in bedding, cows spent 11 min less
      time lying down during each 24-h period. In a third experiment, we imposed 4
      treatments that reflected the variation in sand depth within stalls: 0, 6.2, 9.9,
      and 13.7 cm below the curb. Again, lying times reduced with decreasing bedding,
      such that cows using the stalls with the least amount of bedding (13.7 cm below
      curb) spent 2.33 h less time per day lying down than when housed with access to
      freestalls filled with sand (0 cm below curb).

PMID- 15956302
TI  - Reproductive performance of anestrous dairy cows treated with progesterone and
      estradiol benzoate.
AB  - Anestrus is a major reproduction problem in pasture-based dairy operations that
      results in poorer reproductive outcomes than herdmates detected in estrus before
      the start of the seasonal breeding program. The objective of the current study
      was to assess a combined progesterone and estradiol benzoate treatment program
      including resynchrony with no treatment. Anestrous pasture-fed dairy cattle (n =
      756) in 9 herds were blocked by herd and age and assigned within sequentially
      presented pairs of cows to be treated with an intravaginal progesterone-releasing
      insert for 8 d plus 2 mg of estradiol benzoate injected i.m. at insert insertion
      and 1 mg of estradiol benzoate injected 1 d after insert removal (d -1). Those
      cows detected in estrus from 0 to 3 d had a used progester-one-releasing insert
      reinserted for 6 d commencing on d 16 with 0.5 mg of estradiol benzoate injected
      i.m. 1 d after insert removal (treatment). The other cow within the pair was left
      as an untreated control (control). Treatment increased the risk of insemination
      and pregnancy by 28 d into the breeding program and resulted in conception 15 d
      earlier compared with controls. In contrast, treatment did not increase the risk
      of pregnancy after 56 d into the breeding program or at the end of the breeding
      season. It is concluded that treatment of anestrous dairy cattle with
      progesterone and estradiol benzoate combined with reinsertion of the progesterone
      insert resulted in earlier conception, but no difference in the final pregnancy
      rate compared with no treatment.

PMID- 15956303
TI  - Reduced dry periods and varying prepartum diets alter postpartum ovulation and
      reproductive measures.
AB  - There has been substantial recent interest in shortening dry periods; however,
      the effects of this management change on reproduction have not been adequately
      evaluated. Holstein cows (n = 58) were assigned in a randomized block design to 1
      of 3 treatments: 1) traditional (T) dry period (approximately 56 d) in which cows
      were fed a low energy diet from 56 to 29 d prepartum followed by a moderate
      energy diet for 28 d; 2) shortened (S) dry period (approximately 28 d) in which
      cows were fed continuously a high energy diet; or 3) no planned (N) dry period in
      which cows were fed continuously a high energy diet. All cows received a high
      energy lactation diet after calving. Ovaries were evaluated by ultrasound and
      blood samples collected 3 times weekly beginning at d 6 or 7 postpartum until 7 d
      after second ovulation. Average days from calving until first detection of a 10
      mm follicle were fewer in N (8.0 d) and S (8.9 d) than in T (10.5 d) cows. Time
      from calving to first ovulation was earlier in N (13.2 d) than in S (23.8 d) and
      T (31.9 d) cows. A greater percentage of follicles of the first follicular wave
      ovulated in N (89%; 16/18) than in T (42%; 8/19), with S (62%; 13/21) cows being
      intermediate. Double ovulation rate at the first ovulation was greater in T (61%)
      than N (16%), with S (35%) intermediate. No difference was detected in double
      ovulation rate at second ovulation (13/56). Number of cows with persistent corpus
      luteum (>30 d; 15/56) was not different among groups; however, short luteal
      phases were greater in N (28%; 5/18) than S (0%; 0/20) cows. Days to first
      artificial insemination were fewer in N (69.4 d) and S (68.0 d) than in T (75.0
      d). First-service conception rate was greater in N (55%; 11/20) than in T (20%;
      4/20), with S (26%; 6/23) cows being intermediate. Days open in pregnant cows
      were fewer in N (93.8 d) than in T (145.4 d), with S (121.2 d) cows being
      intermediate. Thus, shortening or eliminating the dry period leads to earlier
      postpartum ovulation and the results highlight the need for future large field
      studies to accurately evaluate the effect of dry period length on reproductive
      performance of lactating dairy cows.

PMID- 15956304
TI  - Effects of estradiol on bovine thecal cell function in vitro: dependence on
      insulin and gonadotropins.
AB  - The objective of this study was to evaluate the influence of estradiol (E2) on
      proliferation and steroid production by thecal cells obtained from large (> or =8
      mm) follicles of cattle. Five experiments evaluated the effect of various doses
      of E2 during a 2-d exposure in serum-free medium on hormone-induced
      steroidogenesis and cell proliferation. In LH-treated thecal cells of experiment
      1, 300 ng/mL of E2 decreased progesterone production by 30% and increased
      androstenedione production to 5.8-fold of controls. In the absence of LH, both 3
      and 300 ng/mL of E2 increased progesterone production. In experiment 2, in the
      presence of insulin and LH, 3, 30, and 300 ng/mL of E2 decreased progesterone
      production (by 17 to 36%), whereas 3 ng/mL of E2 decreased and 300 ng/mL of E2
      increased androstenedione production. Doses of LH (3 to 30 ng/mL) tested in
      experiment 3 increased (to as much as 3.7-fold) progesterone production by thecal
      cells and E2 attenuated this stimulatory effect by 40%. In contrast, E2 amplified
      the stimulatory effect of LH on androstenedione production in experiment 3. In
      experiment 4, E2 (300 ng/mL) decreased IGF-I- and insulin-induced thecal cell
      progesterone production by 70 to 77%, whereas E2 increased basal, IGF-I, and
      insulin-induced androstenedione production. In experiment 5, in the presence of
      insulin, 10 to 1000 ng/mL of E2 had no effect on [(125)I]-IGF-I binding to thecal
      cells, whereas 10 and 100 ng/mL of E2 increased and 1000 ng/mL of E2 decreased
      progesterone production by thecal cells. Estradiol had no consistent effect on
      thecal cell numbers among the 5 experiments. These results support the hypothesis
      that E2 may act as a paracrine factor to directly regulate hormone-induced
      steroid production by thecal cells without affecting cell numbers or numbers of
      insulin-like growth factor type I receptors.

PMID- 15956305
TI  - Effects of induced clinical mastitis during preovulation on endocrine and
      follicular function.
AB  - The objective of the study was to determine if experimentally induced clinical
      mastitis before ovulation resulted in alterations of endocrine function,
      follicular growth, or ovulation. On d 8 (estrus = d 0), cows were challenged
      (TRT; n = 19) with Streptococcus uberis or were not challenged (control; n = 14).
      Forty-eight hours after induction of luteal regression on d 12, blood samples
      were collected to determine estradiol-17beta, LH pulse frequency, and occurrence
      of the LH surge. Ovaries were scanned to monitor follicular growth and ovulation.
      Cows with clinical mastitis (n = 12) had elevated rectal temperatures, somatic
      cell counts, and mammary scores. Estrus and ovulation occurred in 4 of 12
      clinically infected cows and in all control cows. Cows that were challenged but
      did not develop clinical mastitis (n = 5) displayed estrus and ovulated. Due to
      differences in expression of estrus, cows were further subdivided for analyses
      into 4 groups: control, TRT-EST (infected cows that displayed estrus; n = 4), TRT
      NOEST (infected cows that did not display estrus; n = 8), and NOMAS (cows that
      were inoculated but did not develop mastitis; n = 4). Ovulation rate was 100% for
      CON, NOMAS, and TRT-EST compared with 0% for TRT-NOEST cows. Size of the
      ovulatory follicle ("presumed" ovulatory follicle in TRT-NOEST cows) was similar
      for all groups. Frequency of LH pulses was decreased in TRT-NOEST compared with
      CON, TRT-EST, and NO-MAS. Estradiol-17beta increased over time in CON, NO-MAS,
      and TRT-EST cows, but did not increase in TRT-NOEST cows. Cows with clinical
      mastitis may exhibit estrus and ovulate normally or have disruptions in normal
      physiology including decreased LH pulsatility, absence of an LH surge and estrous
      behavior, suppressed estradiol-17beta, and failure to ovulate.

PMID- 15956306
TI  - Effects of seasonal climatic conditions on the diagnosis of Mycobacterium avium
      subspecies paratuberculosis in dairy cattle.
AB  - Validity of Johne's disease programs and control protocols that rely on
      established cut points [e.g., specified sample-to-positive (S/P) ratios] for
      ELISA serological tests depends on interpreted results that are not susceptible
      to variable test accuracy. It was hypothesized that seasonal variability exists
      in serological response to Mycobacterium avium subsp. paratuberculosis (MAP)
      infection. Further, a reciprocal response may occur, resulting in greater risk of
      fecal shedding in subclinically infected animals. A testing regimen was invoked
      that included multiple testing of individual adult cows during the 4 seasons.
      Serum was collected on a cyclic, monthly basis from 3 randomly selected cohorts
      of dairy cows, and fecal samples were collected from the 20% of cows with the
      greatest ELISA test S/P ratios. Staggered, quarterly sampling was continued for 1
      yr, and at the conclusion, serum was analyzed en masse. The ELISA outcome values
      (i.e., S/P ratio) were treated both as categorical and continuous variables. The
      potential lagged effects of temperature-related seasonality on S/P ratio, as well
      as the potential for a change in test result caused by temperature were assessed.
      Results for fecal culture were analyzed on a categorical scale and compared with
      the ELISA results to explore the possibility of reciprocal fecal shedding. No
      significant seasonal effects on either S/P ratios or the proportion of cows
      seropositive to MAP were observed. Furthermore, no evidence was found linking
      temperature-related seasonality to a reciprocal increase in the risk of fecal
      culture positivity for MAP.

PMID- 15956307
TI  - Predicting risk of ketosis in dairy cows using in-line measurements of beta
      hydroxybutyrate: a biological model.
AB  - Automated monitoring of individual cows to determine health status is a
      potentially valuable management tool, especially in large dairy herds. Herein is
      described the rationale, structure, and functionality of a biological model to
      predict risk of ketosis in individual cows using in-line measurements of the
      ketone body beta-hydroxybutyrate (BHBA) in milk. The model also uses acceleration
      in milk yield, body fatness at calving, diseases in current lactation, and
      incidences of ketosis in earlier lactations as additional risk factors for
      ketosis. However, the model is designed to function merely on the basis of milk
      BHBA in the absence of other data. Values of milk BHBA are smoothed using a state
      space model before these are used in calculations in the biological part of the
      model. The model is designed to be updated each time a new BHBA measurement or a
      disease occurrence is available and then uses previous and current data. Outputs
      of the model are the risk of ketosis (value between 0 and 1, where 0 = no risk
      and 1 = clinical ketosis) and how many days until the next milk sample should be
      taken and analyzed for BHBA. At higher risks for ketosis, more frequent milk
      sampling is the recommended output. Test examples from cows for which BHBA has
      been measured extensively were used to show the functionality of the model. The
      model performed equally well when reductions in sampling frequency were applied,
      and it was also relatively robust to the addition of up to +/- 2 residual SD of
      random noise in the BHBA values. This model has the potential to provide the
      basis for a useful disease monitoring and management tool. However, thorough
      validation awaits a much larger dataset and testing of the model under a variety
      of on-farm situations.

PMID- 15956308
TI  - Changes in feeding, drinking, and standing behavior of dairy cows during the
      transition period.
AB  - The aims of this study were to determine how measures of feeding, drinking, and
      standing behavior change over the period around calving, to derive objective meal
      and drinking bout criteria for transition cows, and to describe the within-cow
      consistency of these behavioral measures. Fifteen transition dairy cows were
      monitored from 10 d before until 10 d after calving. Meal criteria were
      calculated for each cow in both the pre- and postcalving periods and varied among
      cows from 5.3 to 105.2 min. There was a tendency for the average number of meals
      per day to be higher after calving than before calving, but time spent eating
      declined from 87 to 62 min/d from the precalving to the postcalving period. Time
      spent drinking before calving averaged 5.5 min/d and increased gradually after
      calving to an average of 6.8 min/d. Total daily standing times remained
      reasonably similar over the transition period but were highest at around calving
      (14.4 h) and lowest during the precalving period (12.3 h). On the day of calving,
      there was a dramatic increase in the number of standing bouts (21.8 bouts)
      compared with the pre- and postcalving averages of 11.7 and 13.1 bouts,
      respectively. In summary, changes in feeding behavior may help account for the
      well-documented changes in feed intake during transition. Documented changes in
      standing behavior suggest that cow comfort may be particularly important during
      the time around calving.

PMID- 15956309
TI  - Performance of dairy cows on Swiss farms with organic and integrated production.
AB  - Milk production of cows on farms in which milk was organically produced (OP)
      tends to be less than that on farms with conventional or integrated production
      (IP), but causes for the difference have not been thoroughly evaluated. We
      performed a study to investigate management, nutritional, metabolic, and
      endocrine risk factors that may be associated with lower milk production on OP
      farms. Fertility traits were also compared. In 60 OP and 60 IP farms, matched in
      size, location, and agricultural zone (altitude), 970 cows were selected. Body
      condition scores (BCS) and body weights (BW) were determined at approximately 29
      d prepartum (visit 1) and at 31 (visit 2) and 102 d postpartum (visit 3). Blood
      was sampled at visit 2 to determine plasma concentrations of glucose,
      nonesterified fatty acids, beta-hydroxybutyrate, albumin, urea, insulin-like
      growth factor-1 (IGF-I), and 3,5,3'-triiodothyronine. Metabolic and endocrine
      traits as well as milk yield, fertility, and feeding factors were compared among
      cows in the 2 production systems. A univariable and stepwise multivariable
      logistic regression model was used to identify risk factors for poor milk yield.
      Energy-corrected milk yield medians and milk urea concentrations were less in OP
      than in IP cows at visits 2 and 3. Organic farms provided less concentrates, and
      OP cows at all visits had lower BW than IP cows. Plasma albumin and urea
      concentrations were lower in OP than IP cows. The following factors were
      positively associated with low milk yield (below median): Simmental breed,
      greater BCS, positive California mastitis test in hindquarters, and sampling
      during summer. Factors associated with an elevated (above median) milk yield
      were: Holstein breed, greater BW and lactation number (age), weak udder
      suspension, greater blood albumin, milk fat and milk protein, more lactation
      persistency, longer calving intervals, routine teat dipping, and more outdoor
      access during winter. In conclusion, significant differences including milk yield
      were detected between Swiss OP and IP cows. Lower milk yields were due to a range
      of individual animal and farm-level factors such as breed, nutrition, management,
      and udder health.

PMID- 15956310
TI  - Relationships between urea dilution measurements and body weight and composition
      of lactating dairy cows.
AB  - The objective of the present study was to investigate the potential of the urea
      dilution technique, coupled with live animal measures to predict the body
      components of dairy cattle. The study involved 104 lactating Holstein-Friesian
      cows offered grass silage-based diets. Urea space volume (USV) was calculated
      from 2 collection periods of blood samples following infusion of urea at 12
      (USV12, kg) and 30 (USV30, kg) min after infusion, and then as a proportion of
      live weight (LW) or empty body weight (EBW). All cows were slaughtered within 2 d
      of the USV trials. Large ranges existed in EBW and empty body concentrations of
      water, crude protein (CP), lipid, ash, and gross energy (GE). The USV12 and USV30
      were both positively related to LW, EBW, and empty body component weights. The r2
      values for USV12 were greater than USV30. The r2 values in the relationships of
      EBW and empty body composition with USV, however, were smaller than those with
      LW. Nevertheless, the relationships were improved when both USV and LW were used
      as predictors, rather than using either alone. Adding milk yield and body
      condition score as supporting predictors to prediction equations using USV and LW
      data for EBW, lipid, and GE contents further improved the relationships (r2 =
      0.93, 0.66, and 0.77, respectively). Internal evaluation of one-third of the
      present data using equations developed from two-thirds of the present data
      indicated that using USV, live weight, and other live animal variables as
      predictors, rather than using USV alone, considerably improved the prediction
      accuracy. It was concluded that USV can be used to predict body composition, but
      the relationships with USV were poorer than those with LW. The USV can only be
      used as a supporting variable to live weight for prediction of body components in
      lactating dairy cows.

PMID- 15956311
TI  - Effects of 2-hydroxy-4-(methylthio) butanoic acid (HMB) and its isopropyl ester
      on milk production and composition by Holstein cows.
AB  - The esterification of 2-hydroxy-4-(methylthio)-butanoic acid (HMB) to isopropanol
      (HMBi) decreases the rate and extent of its ruminal breakdown. The modes of
      action of HMB and HMBi appear to be different. The quantification of the
      production response to HMBi has not been done. The objectives of this study were
      (1) to determine the lactation response to HMB, (2) to determine the lactation
      response to HMBi, and (3) to evaluate whether the response to HMBi is affected by
      HMB in the diet. Sixty-one Holstein cows (24 primiparous, 37 multiparous) were
      assigned to 1 of 4 dietary treatments 21 to 28 d after calving. The base diet
      consisted of [on a dry matter (DM) basis] 32.5% corn silage, 17.5% alfalfa hay,
      10% whole cottonseed, and 40% of a pelleted concentrate made primarily of ground
      corn, soybean meal, and blood meal, and was fed for 16 wk as a control diet. To
      prepare the dietary treatments, the base diet was supplemented with 0.1% of diet
      DM with HMB (treatment 2), with 0.15% HMBi (treatment 3), or with 0.045% HMB and
      0.15% HMBi (treatment 4). Results showed a significant increase in milk yield
      (2.9 kg/d), protein content (0.15%), protein yield (115 g/d), fat yield (165
      g/d), and lactose yield (182 g/d) from HMBi. Supplementation of HMB had small and
      nonsignificant effects on milk yield and composition. There were no significant
      interaction effects of HMB with HMBi on any of the production traits measured in
      this experiment. Plasma free Met as a proportion of essential amino acids was
      increased by HMBi, but not by HMB. Dietary supplementation of HMBi increased
      gross N efficiency expressed as the proportion of ingested N secreted in milk.
      Consequently, HMBi significantly improved N efficiency.

PMID- 15956312
TI  - Adipose tissue metabolism and production responses to calcium propionate and
      chromium propionate.
AB  - The objective was to determine action of calcium propionate and chromium
      propionate on lipogenesis and lipolysis in adipose tissue, dry matter (DM)
      intake, milk production and composition, and serum glucose and free fatty acids
      in Holstein dairy cattle treated from 21 d prepartum to 35 d postpartum. Twelve
      multiparous animals were assigned to each treatment: control (C), calcium
      propionate (CaP, 0.125 kg/d), chromium propionate (CrP, 10 mg of trivalent Cr/d),
      and both. All animals were switched to control at 36 days in milk (DIM) and the
      trial continued to 90 DIM. Biopsies of adipose tissue were taken at -7, 14, 28,
      and 56 d from calving. Control intake prepartum was 10.6 +/- 2 kg/d. Calcium
      propionate increased DM intake 11% prepartum and 13% postpartum; CrP increased DM
      intake 7 and 16%; and the combination treatment had no effect. Milk yield was
      44.2 kg/d for controls and 46.8 kg/d for d 1 to 90 for CrP-treated cows. Adipose
      tissue lipogenesis in cows treated with either CaP or CrP was 1.25 to 78 times as
      fast as controls from 14 to 56 d and had returned to prepartum rates by 56 d.
      From 14 to 28 d, basal lipolysis in CaP- or CrP-treated cows ranged from 27 to
      102% of control, whereas stimulated lipolysis was 61 to 113% of control. Milk fat
      yield was 92 to 95% of control on calcium and chromium propionate; the difference
      was similar to the net reduction in adipose lipolysis. Milk lactose, protein, and
      solids-not-fat did not differ among treatments. Providing a small amount of
      gluconeogenic precursors may reduce net lipolysis, allowing increased feed intake
      and milk production. The effect is thought to be through chromium acting to
      increase glucose flux into adipocytes.

PMID- 15956313
TI  - Effects of cinnamaldehyde and garlic oil on rumen microbial fermentation in a
      dual flow continuous culture.
AB  - Eight continuous culture fermentors inoculated with ruminal liquor from heifers
      fed a 50:50 alfalfa hay:concentrate diet (17.6% crude protein, 28.0% neutral
      detergent fiber) were used in 3 replicated periods to study the effects of
      cinnamaldehyde (CIN) and garlic oil (GAR) on rumen microbial fermentation.
      Treatments were no additive (negative control); 1.25 mg/L (MON) and 12.5 mg/L
      (MON10) of the ionophore antibiotic monensin (positive control); 31.2 mg/L CIN
      (CIN) and 312 mg/L (CIN10) of CIN; and 31.2 mg/L GAR (GAR) and 312 mg/L (GAR10)
      of GAR (Allium sativa). The MON10 caused expected changes in microbial
      fermentation patterns (a decrease in fiber digestion, ammonia N concentration,
      and proportions of acetate and butyrate; an increase in the proportion of
      propionate; and a trend to increase small peptide plus AA N concentration). The
      CIN decreased the proportion of acetate and branch-chained volatile fatty acids
      (VFA) and increased the proportion of propionate; CIN10 decreased the proportion
      of acetate and increased the proportion of butyrate compared with the control.
      The GAR10 increased the proportion of propionate and butyrate and decreased the
      proportion of acetate and branch-chained VFA compared with the control. The GAR10
      also increased the small peptide plus amino acid N concentration, although no
      effects were observed on large peptides or ammonia N concentrations. The CIN and
      GAR10 resulted in similar effects as monensin, with the exception of the effects
      on the molar proportion of butyrate, which suggests that they might have a
      different mode of action in affecting in vitro microbial fermentation.

PMID- 15956314
TI  - Dietary manganese for dry and lactating Holstein cows.
AB  - Apparent digestibility and retention of Mn by dairy cows was used to compare 2
      sources of Mn and to estimate Mn requirements. In experiment 1, Holstein cows at
      dry-off (60 d prepartum) were fed a basal diet with no supplemental Mn (43 mg of
      Mn/kg of dry matter) and received a daily bolus of 0 or 200 mg/d supplemental Mn
      from MnSO4 or from Mn-Met (6 cows per treatment) until parturition. Approximately
      30 d before parturition, cows were moved to metabolism stalls for total
      collection of feces and urine. No differences were observed between Mn sources,
      but apparent absorption of Mn (6.4 vs. 2.3%) tended to be greater, and apparent
      retention of Mn (44 vs. 12 mg/d) was greater, for cows given supplemental Mn
      compared with control cows. In the second experiment, apparent Mn digestibility
      data from 8 experiments conducted with lactating dairy cows (39 dietary
      treatments and 160 observations) were combined with data from experiment 1. The
      regression equation of intake of digestible Mn on Mn intake (i.e., Lucas test)
      was as follows: intake of digestible Mn (mg/d) = -151 + 0.26 x Mn intake (mg/d).
      Based on that equation, Mn intake had to equal 580 mg/d to meet the metabolic
      fecal Mn requirement. The corresponding dietary concentration, assuming dry
      matter intakes of 21 and 12 kg/d for lactating and dry cows, respectively, were
      28 and 49 mg/kg dry matter. These concentrations are approximately 1.6 and 2.7
      times higher than those needed to meet the Mn requirements for lactating and dry
      cows, respectively, as calculated using the 2001 National Research Council dairy
      requirements model.

PMID- 15956315
TI  - Effects of BioChlor and Fermenten on microbial protein synthesis in continuous
      culture fermenters.
AB  - Meta analysis models were constructed from a data-set of 15 continuous culture
      fermenter trials and 118 observations on studies with either BioChlor (n = 23
      observations) or Fermenten (n = 95) included at 10 and 3%, respectively, of
      dietary dry matter (DM) to evaluate effects of the ingredients BioChlor and
      Fermenten (B/F) on rumen function. Digestibility of crude protein was
      significantly increased by 11% with B/F treatment. This was reflected in
      significant increases in digestibility of DM and organic matter (OM) by 3.6 and
      7.9%, respectively. Increased amounts of sugar in the diet in the presence of B/F
      tended to reduce digestibility of non-structural carbohydrates (NSC); however,
      the net effect on NSC digestion was small. There was no effect of treatment on
      most individual volatile fatty acids (VFA) or total VFA production. Propionate
      production, however, was significantly reduced in treated fermenters. The main
      effect of B/F as well as of starch and soluble fiber when combined with the
      treatment was to increase propionate production; however, the interaction between
      B/F treatment and sugar decreased propionate production markedly, resulting in a
      net decrease. The acetate-to-propionate ratio increased by 6% with B/F, largely
      as a result of the decrease in propionate. Production of nonammonia nitrogen was
      1% less in B/F-treated fermenters, and interactions between treatment and starch,
      sugar, or soluble fiber were significant. Treated fermenters produced 15.7% more
      microbial nitrogen, in association with a significant 37% increase in rumen
      protein digestion. Interactions between treatment and starch, soluble fiber, or
      sugar influenced these results. The interaction of B/F and sugar resulted in a
      decrease in undegradable protein N and an increase in microbial nitrogen
      production. Ammonia nitrogen concentrations were increased by 24.6% in treated
      fermenters. Efficiency of microbial nitrogen production from DM, OM, or
      carbohydrate was significantly increased by B/F. Sugar content increased
      efficiency of microbial protein production/kg of OM digested or carbohydrate
      digested in the presence of treatment by >10 times the increase that was
      attributable to the interaction of treatment with starch. Treatment with B/F
      reduced moles of VFA produced/kg of microbial nitrogen produced by 16%. This
      effect was also substantially influenced by interactions between B/F and sugar.
      If the fermenter results are representative of those in vivo, milk production
      responses to treatment with B/F will depend on amounts of starch, soluble fiber,
      and, particularly, sugar in diets. Milk production responses will also depend on
      the quality of protein in the diet and the comparative benefit that increased
      flux of microbial nitrogen provides. Increased digestibility of OM should allow
      additional ruminant production benefits.

PMID- 15956316
TI  - Varying protein and starch in the diet of dairy cows. I. Effects on ruminal
      fermentation and intestinal supply of nutrients.
AB  - The main objective of this experiment was to examine the effects of the
      percentage and source of crude protein (CP) and the amount of starch in the diet
      of dairy cows on ruminal fermentation, nutrient passage to the small intestine,
      and nutrient digestibility. For this purpose, 6 multiparous Holstein cows
      fistulated in the rumen and duodenum that averaged 73 d in milk were used in a 6
      x 6 Latin square design with a 2 x 3 factorial arrangement of treatments. Two
      sources of CP [solvent-extracted soybean meal (SBM) and a mixture of SBM and a
      blend of animal-marine protein supplements plus ruminally protected Met (AMB)]
      and 3 levels of dietary protein (about 14, 16, and 18%) were combined into 6
      treatments. On a dry matter (DM) basis, diets contained 25% corn silage, 20%
      alfalfa silage, 10% cottonseed, 26.7 to 37% corn grain, and 4 to 13.5% protein
      supplement. Intakes and digestibilities in the rumen and total tract of DM,
      organic matter, acid and neutral detergent fiber were unaffected by treatments.
      Increasing dietary CP from 14 to 18% decreased the intake and apparent ruminal
      and total tract digestion of starch, but increased the proportion of starch
      consumed by the cows that was apparently digested in the small intestine. At 14%
      CP, starch intake and total tract digestion were higher for the AMB diet than for
      the SBM diet, but the opposite occurred at 16% CP. Across CP sources, increasing
      CP in the diet from 14 to 18% increased the intakes of N and amino acids (AA),
      and ruminal outflows of nonammonia N, nonammonia nonmicrobial N, each individual
      AA except Met, total essential AA, and total AA. Across CP percentages, replacing
      a portion of SBM with AMB increased the intake of Met and Val and decreased the
      concentration of ammonia N in the rumen, but did not affect the intake of other
      essential AA or the intestinal supply of any essential AA and starch. The ruminal
      outflow of microbial N, the proportional contribution of Lys and Met to total AA
      delivered to the duodenum, and milk yield were unaffected by treatments. Data
      suggest that the intake of N by high-producing dairy cows that consume sufficient
      energy and other nutrients to meet their requirements can be decreased to about
      600 to 650 g daily without compromising the supply of metabolizable protein if
      the source and amount of dietary CP and carbohydrate are properly matched.

PMID- 15956317
TI  - Varying protein and starch in the diet of dairy cows. II. Effects on performance
      and nitrogen utilization for milk production.
AB  - The main objective of this experiment was to examine the effects of the
      percentage and source of crude protein (CP) and the amount of starch in the diet
      of dairy cows on the lactational performance and use of N for milk production.
      Sixty multiparous Holstein cows were used in a 210-d lactational trial with a
      completely randomized design with a 2 x 3 factorial arrangement of treatments.
      Two sources of CP [solvent-extracted soybean meal (SBM) and a mixture of SBM and
      a blend of animal-marine protein supplements plus ruminally protected Met (AMB)]
      and 3 levels of dietary CP (means = 14.8, 16.8, and 18.7%) were combined into 6
      treatments. On a dry matter (DM) basis, diets contained 25.0% corn silage, 20.0%
      alfalfa silage, 10.0% cottonseed, 26.7 to 37.0% corn grain, and 4.8 to 13.5%
      protein supplement, plus minerals and vitamins. Across the 210 d of lactation,
      the productive response of dairy cows to the source of supplemental CP depended
      on the concentration of CP in the diet. At 18.7% CP, cows fed SBM consumed more
      DM and produced more milk, 3.5% fat-corrected milk, fat, and true protein, but
      had lower efficiency of feed use and body condition score than cows fed AMB. At
      16.8% CP, cows fed AMB produced more 3.5% fat-corrected milk, fat, and true
      protein than cows fed SBM. At 14.8% CP, cows fed SBM consumed more DM but
      produced less true protein and had lower feed efficiency than cows fed AMB.
      Across CP sources, cows fed 14.8% CP produced less fat-corrected milk and true
      protein than cows fed 16.8 and 18.7% CP. Across CP percentages, cows fed AMB
      produced more fat-corrected milk per kilogram of DM consumed than cows fed SBM.
      Despite these interactions, improvements in the gross efficiency of N use for
      milk production were achieved through reductions in the intake of N independently
      of the source of CP. Data suggest that the intake of N by high-producing dairy
      cows that consume sufficient energy and other nutrients to meet their
      requirements can be decreased to about 600 to 650 g daily if the source of RDP
      and RUP are properly matched with the source and amount of carbohydrate in the
      diet.

PMID- 15956318
TI  - Preventing bacterial contamination and proliferation during the harvest, storage,
      and feeding of fresh bovine colostrum.
AB  - The objectives of this study were to identify control points for bacterial
      contamination of bovine colostrum during the harvesting and feeding processes,
      and to describe the effects of refrigeration and use of potassium sorbate
      preservative on bacteria counts in stored fresh colostrum. For objective 1, first
      milking colostrum samples were collected aseptically directly from the mammary
      glands of 39 cows, from the milking bucket, and from the esophageal feeder tube.
      For objective 2, 15-mL aliquots of colostrum were collected from the milking
      bucket and allocated to 1 of 4 treatment groups: 1) refrigeration, 2) ambient
      temperature, 3) refrigeration with potassium sorbate preservative, and 4) ambient
      temperature with potassium sorbate preservative. Subsamples from each treatment
      group were collected after 24, 48, and 96 h of storage. All samples underwent
      bacteriological culture for total plate count and coliform count. Bacteria counts
      were generally low or zero in colostrum collected directly from the gland [mean
      (SD) log10 cfu/mL(udder) = 1.44 (1.45)]. However, significant bacterial
      contamination occurred during the harvest process [mean (SD) log10 cfu/mL(bucket)
      = 4.99 (1.95)]. No additional bacterial contamination occurred between the bucket
      and the esophageal feeder tube. Storing colostrum at warm ambient temperatures
      resulted in the most rapid increase in bacteria counts, followed by intermediate
      rates of growth in nonpreserved refrigerated samples or preserved samples stored
      at ambient temperature. The most effective treatment studied was the use of
      potassium sorbate preservative in refrigerated samples, for which total plate
      count and total coliform counts dropped significantly and then remained constant
      during the 96-h storage period.

PMID- 15956319
TI  - In vitro embryo production: growth performance, feed efficiency, and
      hematological, metabolic, and endocrine status in calves.
AB  - The potential management benefits of in vitro embryo production have been offset
      by an increased incidence of health-related problems in resulting calves
      [increased birth weight, congenital abnormalities, and peri- and postnatal
      mortality (large-offspring syndrome)] and of recipient cows (prolonged gestation,
      dystocia, increased hydroallantois, abortion). The aim of the present research
      was to determine whether relevant metabolic, endocrine, or hematological traits
      could be related to the causes of enhanced growth performance of in vitro
      fertilized calves. Growth performance and feed efficiency as well as
      hematological, metabolic, and endocrine traits studied in calves derived from in
      vitro-produced embryos (IVP; n = 11) and in calves derived from artificial
      insemination (AI; n = 8). Donor cows from which oocytes for in vitro
      fertilization were obtained had a heterogeneous background, thus excluding
      genetic maternal influences. On the other hand, semen for in vitro fertilization
      and for artificial insemination was from the same bull, and recipient cows were
      held under the same husbandry and feeding conditions as AI cows, thus reducing
      the variability. Blood samples were collected preprandially on d 1, 2, 3, 4, 7,
      14, 28, 56, and 112 of life and every 20 min between 0830 and 1630 h on d 7 and
      112 for the evaluation of growth hormone secretory patterns. Gestation of IVP
      cows was longer than that of AI cows, but birth weights were similar in both
      groups. Feed intake, average daily gain, and body length during the experimental
      period, body weight from wk 8 to 16, and gain/feed ratio during the first month
      of life were higher in IVP than in AI calves. At birth, potassium, 3,5,3'
      triiodothyronine, and thyroxine concentrations were lower in IVP than in AI
      calves. Concentrations of sodium and potassium on d 7, of triglycerides on d 28,
      and of albumin on d 56 were higher in IVP than in AI calves. In conclusion, IVP
      calves had higher feed intake and growth rate during the entire growth period and
      improved feed efficiency in the first month of life than AI calves, but this was
      not mirrored by consistent changes of hematological, metabolic, or endocrine
      traits, whose concentrations were in the normal range. Additional work is needed
      to study IVP calves under field conditions.

PMID- 15956320
TI  - Influence of living and autoclaved yeasts of Saccharomyces boulardii on in vitro
      ruminal microbial metabolism.
AB  - Experimental data on the effects of Saccharomyces boulardii on rumen microbial
      metabolism are scarce. The aim of this study was to examine whether S. boulardii
      had an effect on parameters of rumen microbial metabolism at different dosages
      and whether the yeast would be suitable as a probiotic agent for ruminants. To
      test whether the potential positive effects of S. boulardii could be attributed
      to the yeast's viability or to its content of nutrients, living and autoclaved
      yeasts were tested simultaneously. For this purpose, incubation trials were
      carried out using the long-term rumen simulation technique. Living and autoclaved
      yeasts were added to fermentation vessels at a concentration of 0.5 or 1.5 g/d.
      The addition of living and autoclaved yeasts stimulated microbial metabolism,
      with no major differences between the treatments. It was concluded that ruminal
      microbes digested the supplied yeast of S. boulardii as an additional substrate
      and that S. boulardii, at least in ruminants, is utilized as a prebiotic rather
      than as a probiotic agent.

PMID- 15956321
TI  - Short communication: Amino acids antagonistic to the amino acids inhibitory for
      growth rate of mixed ruminal bacteria.
AB  - Antagonism of some amino acids (AA) to the inhibitory effects of other AA (Ile,
      Phe, and Thr) on the growth rate of mixed ruminal bacteria was investigated. In
      vitro growth rate of the mixed ruminal bacteria was inhibited when the 3
      inhibitory AA (1 mM each) were each added to individual control treatments in
      which an ammonium salt was included as a sole N source. The inhibitory effect
      caused by Ile was relieved by addition of Leu or Val (equimolar to Ile), and no
      significant inhibition was shown when both Leu and Val were added together with
      Ile. The growth inhibition caused by Phe was also alleviated by supplementing
      with Trp, and was completely negated by adding Tyr. The inhibitory effect of Thr,
      on the other hand, was not affected by addition of Lys or Met (which are
      synthesized using a common pathway with Thr), but was mitigated by
      supplementation with Glu, Ser, Val, Ala, or Gln. Among the antagonistic AA, Leu,
      Val, Trp, Tyr, and Glu were indispensable for the maximum growth rate of the
      ruminal bacteria under the experimental condition of supplementation of amino-N,
      the removal of which from a mixture of 20 protein AA caused the growth rate to
      decline. Removals of Ile along with Leu or Val or both, of Phe along with Trp or
      Tyr, and of Thr along with Glu recovered the promotion of bacterial growth rate.
      It was concluded that inhibitions of the bacterial growth rate caused by Ile,
      Phe, or Thr could be antagonized by some other AA (Leu, Val, Tyr, Trp, or Glu),
      and the role of these latter AA as relievers of the inhibitory effects could
      explain why they are indispensable for maximum growth rate of ruminal bacteria.

PMID- 15956322
TI  - The effect of diets on milk production and composition, and on lactation curves
      in pastured dairy goats.
AB  - A 2-yr study investigated effects of different levels of concentrate
      supplementation on milk production, composition, and lactation curves in pastured
      dairy goats. For both years, 44 Alpine goats (Capra hircus; 55 +/- 11 kg body
      weight) were randomly allocated to 4 groups. Animals were supplemented with 0.66
      (treatments A and B), 0.33 (treatment C), or 0 kg of concentrate (treatment D)
      per kg of milk over 1.5 kg/d. Mixed vegetative forages were rotationally grazed
      by the goats (treatments B, C, and D), except that treatment A was confined and
      fed alfalfa hay. Individual milk production was recorded daily, and milk samples
      were collected once every 2 wk for the 7-mo period (March to September) and
      analyzed for fat, protein, lactose, urea-N, nonesterified fatty acids, and
      allantoin (second year only). Milk yield and composition varied among dietary
      treatments, with some measures affected by year. Average daily milk yield was
      lowest for treatment D. The increased level of concentrate supplementation in
      treatment A led to 22% greater milk yield compared with treatment D. Milk
      production increased by 1.7 and 0.9 kg for each additional kilogram of
      concentrate fed per day during the first and second years, respectively. Average
      peak yield, time of peak yield, and persistency were lower for treatment D than
      for other treatments. The percentage of milk fat was lower for treatment D than
      for other treatments. Concentration of milk protein was greater for treatments A
      and B during the first year, and was higher for treatment C than for other
      treatments during the second year. Average milk lactose concentration was higher
      for treatments B and C than for other treatments. However, milk urea-N
      concentration in treatment A was higher than other treatments. Milk allantoin,
      used to estimate microbial proteins synthesis, was 20 to 25% greater for
      treatment A than for other treatments. Averaged across year, plasma urea-N and
      nonesterified fatty acids concentration were lowest for treatment B. Average
      organic matter intake was similar among treatments during both years. Ratios of
      acetate and propionate concentrations for treatment A were lowest among
      treatments. In conclusion, milk production and composition were affected by the
      feeding treatment and year. Increased level of nutrition lead to an increase in
      daily milk yield, peak yield, time of peak yield, and persistency compared with
      treatment D. Alpine dairy goats grazing on fresh forages without concentrate
      supplementation can produce milk inexpensively, and response to concentrate
      supplementation is greater for low quality pasture.

PMID- 15956323
TI  - Genetic profile of total body energy content of Holstein cows in the first three
      lactations.
AB  - Weekly total body energy content (TBEC) was calculated for 444 Holstein cows in
      their first 3 lactations. These calculations were based on body lipid and protein
      changes predicted from weekly changes in body condition score and live weight of
      each cow. In first lactation, cows lost TBEC during the initial 8 wk, regained it
      by wk 22, and continued to build up their reserves until wk 37. Cows started
      lactations 2 and 3 with considerable reserves from the dry period that they used
      during the first 13 wk of lactation. Variance components for TBEC were estimated
      using random regression analysis allowing for heterogeneous residual variance.
      The genetic variance increased within each lactation, suggesting that the genetic
      component becomes more important as lactation progresses. The genetic
      correlations between very early (wk 1 to 4) and later stages of first lactation
      were near zero but they increased considerably between later lactation stages.
      Genetic correlations between TBEC on wk 5 of first lactation and the remainder of
      this lactation ranged from 0.64 for the more distant weeks to 0.99 for the
      immediately subsequent weeks. Genetic correlations with TBEC in second lactation
      were moderately high (0.68 to 0.70) for the early weeks (1 to 8) and decreased
      gradually to 0.56 for weeks at the end of lactation. For third lactation, these
      estimates ranged from 0.53 to 0.63. Genetic correlation estimates of TBEC in wk
      12 of first lactation with subsequent first-lactation weeks varied from 0.79 to
      0.99, whereas they ranged from 0.65 to 0.77 and from 0.57 to 0.68 in second and
      third lactations, respectively. The genetic correlation between TBEC in later
      weeks of first lactation and the rest of productive life increased as first
      lactation progressed, but the improvement diminished. Weekly genetic evaluations
      for first-lactation TBEC were used to predict second- and third-lactation energy
      content. The accuracy of these predictions increased with progressing weeks in
      first lactation, but about three-fourths of the improvement occurred by wk 5. Our
      results suggest that TBEC calculated after a month from the first calving may
      give useful information about the future energy content of a cow.

PMID- 15956324
TI  - Accuracy and stability of national and international somatic cell score
      evaluations.
AB  - Somatic cell score (SCS) evaluations have been published in the United States
      since 1994 and international evaluations have been available through Interbull
      since May 2001. The accumulated data provides an opportunity to investigate the
      accuracy and stability of SCS evaluations. United States domestic evaluations
      from January 1995 through August 2004, for 21,500 Holstein bulls were considered,
      over time and sequentially within bull, for changes to the November 2004
      evaluation. On average, predicted transmitting ability (PTA) SCS increased
      (worsened) by 0.002 from earlier evaluations to November 2004. Although bias was
      small, PTA changes were more than expected based on change in reliability. When
      looked at sequentially, bulls' earlier evaluations were generally lower (i.e.,
      merit was overestimated) relative to November 2004. Differences were small, and
      PTA SCS increased steadily with the addition of second-crop daughters. All
      524,081 evaluations were considered pairwise providing over 8,000,000 pairs of
      bulls' evaluations for analysis of PTA differences relative to change in
      reliability. Agreement of observed and expected SD improved for larger changes in
      reliability. The November 2004 US and Interbull PTA were matched with US and
      Interbull PTA from May 2001 (US04, IB04, US01, and IB01, respectively) for 14,652
      Holstein bulls. For bulls having only US daughters in IB01, correlations were
      similar for US01 and IB01 with US04, and IB01 with IB04. Corresponding
      regressions were all nearly 1.00. For bulls also having nonUS daughters in IB01,
      correlations with yield deviations calculated for later daughters (used as source
      of independent data) were higher (0.747 vs. 0.714) for IB01 than for US01. For
      bulls with added US daughters, correlation with US04 was also higher for IB01
      than US01, showing that inclusion of foreign data improved predictive value of
      SCS evaluations.

PMID- 15956325
TI  - Evaluation of autoregressive covariance structures for test-day records of
      Holstein cows: estimates of parameters.
AB  - The objective of this study was to compare test-day (TD) models with
      autoregressive covariance structures for the estimation of genetic and
      environmental components of variance for milk, fat and protein yields, and
      somatic cell score (SCS) in Holstein cows. Four models were compared: model I (CS
      model) was a simple TD repeatability animal model with compound symmetry
      covariance structure for environmental effects, model II (ARpe model) and model
      III (ARe model) had first-order autoregressive covariance structures for TD
      permanent or residual environmental effects, respectively, and model IV (305-d
      model) was a simple animal model using 305-d records. Data were 106,472 first
      lactation TD records of 12,071 Holstein cows calving from 1996 through 2001.
      Likelihood ratio tests indicated that ARpe and ARe models fit the data
      significantly better than the CS model. The ARe model resulted in slightly
      smaller estimates of genetic variance and heritability than did the CS model.
      Estimates of residual variance were always smaller with the CS model than with
      the ARe model with the autoregressive covariance structure among TD residual
      effects. Estimates of heritability with different TD models were in the range of
      0.06 to 0.11. The 305-d model resulted in estimates of heritability in the range
      of 0.11 to 0.36. The autoregressive covariance structure among TD residual
      effects may help to prevent bias in heritability estimates for milk, fat and
      protein yields, and SCS.

PMID- 15956326
TI  - In vitro peripheral blood mononuclear cell proliferation in a crossbred cattle
      population.
AB  - Immune function measured by Staphylococcus aureus- and phytohemagglutinin- (PHA-)
      induced cell proliferation was assessed in a population of 445 genetically
      defined, F2 and backcross Charolais-Holstein crossbred cattle when the animals
      were approximately 5 mo of age. Variation in Staph. aureus-induced, PHA-induced,
      and control proliferation [peripheral blood mononuclear cell (PBMC) and media
      only] was observed at d 2, 3, 4, 5, 9, and 10 of in vitro culture. The levels of
      Staph. aureus-induced, PHA-induced, and control proliferation were strongly
      positively correlated between days of culture within-assay (e.g., between d 2 and
      d 3 or between d 4 and d 5). Responses were also positively correlated when the
      same individuals were resampled and the assay repeated within 3 mo. Analyses
      fitting linear mixed models using REML showed that Staph. aureus-induced and PHA
      induced proliferation was significantly associated with control proliferation and
      the year of birth. The age of the animal at sampling influenced only Staph.
      aureus-induced proliferation, with Staph. aureus-induced proliferation increasing
      with the age of the animal. Control proliferation was influenced by a sex x cross
      interaction, although in this study, sex was confounded by management, as female
      cattle were housed and reared differently from male cattle. All 3 measures of
      immune function were influenced by sire, demonstrating that these traits are
      partially under genetic control, and indicating that it may ultimately be
      possible to identify quantitative trait loci for these measures of immunity.

PMID- 15956327
TI  - A Bayesian threshold-normal mixture model for analysis of a continuous mastitis
      related trait.
AB  - Mastitis is associated with elevated somatic cell count in milk, inducing a
      positive correlation between milk somatic cell score (SCS) and the absence or
      presence of the disease. In most countries, selection against mastitis has
      focused on selecting parents with genetic evaluations that have low SCS.
      Univariate or multivariate mixed linear models have been used for statistical
      description of SCS. However, an observation of SCS can be regarded as drawn from
      a 2- (or more) component mixture defined by the (usually) unknown health status
      of a cow at the test-day on which SCS is recorded. A hierarchical 2-component
      mixture model was developed, assuming that the health status affecting the
      recorded test-day SCS is completely specified by an underlying liability
      variable. Based on the observed SCS, inferences can be drawn about disease status
      and parameters of both SCS and liability to mastitis. The prior probability of
      putative mastitis was allowed to vary between subgroups (e.g., herds, families),
      by specifying fixed and random effects affecting both SCS and liability. Using
      simulation, it was found that a Bayesian model fitted to the data yielded
      parameter estimates close to their true values. The model provides selection
      criteria that are more appealing than selection for lower SCS. The proposed model
      can be extended to handle a wide range of problems related to genetic analyses of
      mixture traits.

PMID- 15956328
TI  - Management of Wisconsin dairy herds enrolled in milk quality teams.
AB  - A study was conducted to characterize Wisconsin dairy herds that enrolled in a
      team-based milk quality improvement program and to assess association of specific
      management practices with milking efficiency and milk quality. Management and
      financial data were obtained from dairy farms (n = 180) that participated in the
      program. Upon enrollment, herds reported a median bulk milk somatic cell count
      (SCC) of 333,500 cells/mL, an average of 125 lactating cows, and a mean rolling
      herd average of 10,100 kg. Many management practices and bulk milk SCC were
      strongly associated with herd size and facility type. Managers of herds housed in
      freestall barns adopted more standardized procedures and recommended management
      practices compared with managers of herds housed in stall barns. Those managers
      also reported less bulk milk SCC and greater milk yields, and had a tendency for
      lower prevalence of subclinical mastitis and reduced estimates of the incidence
      of clinical mastitis. Managers of freestall herds received more quality premiums
      for milk shipped, estimated that they had fewer financial losses related to
      mastitis, and reported more efficient milking performance. A more efficient
      milking performance did not increase estimates of clinical mastitis or bulk milk
      SCC. In herds having freestalls, frequent training of employees seemed to be the
      fundamental factor that increased milking efficiency. Bulk milk SCC was
      positively associated with standard plate count, estimated rate of clinical
      mastitis, prevalence of subclinical mastitis, numbers of cows culled for
      mastitis, and estimated financial losses attributable to mastitis. Herds
      reporting high bulk milk SCC had an increased prevalence of subclinical mastitis,
      but incidence did not differ among bulk milk SCC categories. Overall, herds did
      not discuss milk quality frequently with dairy professionals, and herds having
      greater bulk milk SCC reported less consultation with their herd veterinarian.

PMID- 15956329
TI  - Actions and outcomes of Wisconsin dairy farms completing milk quality teams.
AB  - Actions and outcomes of Wisconsin dairy farms (n = 113) that completed a team
      based milk quality improvement program were assessed. Selection of milk quality
      goals and adoption of management actions were evaluated. Management and financial
      data related to milk quality were compared between the beginning and end of the
      milk quality program. Milk quality premiums were reported to be the largest
      financial opportunity related to milk quality and reduction of bulk milk somatic
      cell count (SCC) was the most commonly listed goal. Recommended management
      practices were highly adopted upon completion of the program. Operators of herds
      housed in freestalls that were not using a recommended management practice at the
      beginning of the program were more likely to adopt it during the program than
      were operators of herds housed in stallbarns. Use of written protocols for
      treatment of clinical mastitis, microbiological analysis of milk obtained from
      cows having clinical mastitis, frequent training of milking personnel, and
      scheduled milking system analysis occurred more often in herds housed in
      freestalls. In general, herds completing the milk quality program reported
      significant reductions in measures of clinical and subclinical mastitis, reduced
      bacterial counts in bulk milk, and reduced culling of cows because of mastitis.
      At the end of the program, increased milk quality premiums and decreased losses
      attributable to mastitis resulted in improved estimates of financial performance.
      Herds beginning the program having high bulk milk SCC had greater improvements in
      milk quality during the program, including a greater reduction in bulk milk SCC
      and fewer losses attributable to mastitis. The majority of the herds considered
      themselves successful in achieving their goals for milk quality and intended to
      continue meeting with their teams.

PMID- 15956331
TI  - Quantitative real-time RT-PCR--a perspective.
AB  - The real-time reverse transcription polymerase chain reaction (RT-PCR) uses
      fluorescent reporter molecules to monitor the production of amplification
      products during each cycle of the PCR reaction. This combines the nucleic acid
      amplification and detection steps into one homogeneous assay and obviates the
      need for gel electrophoresis to detect amplification products. Use of appropriate
      chemistries and data analysis eliminates the need for Southern blotting or DNA
      sequencing for amplicon identification. Its simplicity, specificity and
      sensitivity, together with its potential for high throughput and the ongoing
      introduction of new chemistries, more reliable instrumentation and improved
      protocols, has made real-time RT-PCR the benchmark technology for the detection
      and/or comparison of RNA levels.

PMID- 15956332
TI  - Intra-domain communication between the N-terminal and DNA-binding domains of the
      androgen receptor: modulation of androgen response element DNA binding.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor that
      recognises and binds to specific DNA response elements upon activation by the
      steroids testosterone or dihydrotestosterone. In vitro, two types of response
      element have been characterised - non-selective elements that bind the androgen,
      glucocorticoid and progesterone receptors, and androgen receptor-selective
      sequences. In the present study, the allosteric effects of DNA binding on the
      receptor amino-terminal domain (NTD) were studied. Binding to both types of DNA
      response element resulted in changes in the intrinsic fluorescence emission
      spectrum for four tryptophan residues within the AR-NTD and resulted in a more
      protease-resistant conformation. In binding experiments, it was observed that the
      presence of the AR-NTD reduced the affinity of receptor polypeptides for binding
      to both selective and non-selective DNA elements derived from the probasin, PEM
      and prostatin C3 genes respectively, without significantly altering the protein
      base pair contacts. Taken together, these results highlight the role of intra
      domain communications between the AR-NTD and the DNA binding domain in receptor
      structure and function.

PMID- 15956333
TI  - Pharmacogenetic analysis of human steroid 5 alpha reductase type II: comparison
      of finasteride and dutasteride.
AB  - Human steroid 5 alpha-reductase type II is a prostate-specific, membrane
      associated enzyme that catalyzes the conversion of testosterone to
      dihydrotestosterone, the most potent androgen in the prostate gland. Genetic
      variants of this enzyme have been associated with both the development and the
      progression of prostate cancer. Both finasteride and dutasteride are competitive
      inhibitors of the type II steroid 5 alpha-reductase that have been effectively
      used for the treatment of benign prostatic hyperplasia. Finasteride has also been
      successfully utilized for prostate cancer chemoprevention. We here investigate 5
      alpha-reductase inhibition assays in vitro to measure the effect of incubation
      time on the apparent inhibition constant (Ki) for both constitutional and somatic
      (prostate cancer) enzyme variants. Our systematic pharmacogenetic analysis shows
      that both finasteride and dutasteride are slow, time-dependent inhibitors of
      steroid 5 alpha-reductase type II, and that the inhibition kinetics depend on the
      5 alpha-reductase genotype. We also show that, overall, dutasteride is a more
      efficient steroid 5 alpha-reductase inhibitor than finasteride. Based on our
      data, we are able to map areas of the enzyme that are responsible for this time
      dependent inhibition for either (or both) enzyme inhibitor(s). This comprehensive
      pharmacogenetic analysis of steroid 5 alpha-reductase variants unveiled
      significant pharmacogenetic variation for both finasteride and dutasteride and
      thus should be taken into account when designing protocols for treatment and/or
      chemoprevention of prostatic diseases with either one of these 5 alpha-reductase
      inhibitors since there is considerable pharmacogenetic variation for both drugs.

PMID- 15956334
TI  - Expression of glutaredoxin (thioltransferase) in the rat ovary during the
      oestrous cycle and postnatal development.
AB  - Glutaredoxins (Grxs) are low-molecular-weight proteins which participate in redox
      events in association with glutathione (GSH) and are involved in a variety of
      cellular processes. It is known that oxidative stress plays important
      physiological roles within the ovary. In the present study, we have prepared
      specific antibodies against rat Grx and have used them to localize the protein in
      the ovaries of rats during postnatal development and during the oestrous cycle,
      by immunohistochemical methods. We have also performed a quantitative analysis of
      Grx by ELISA and Western blotting in homogenates of whole ovaries of cycling and
      pseudopregnant rats. We have found a prominent presence of Grx in the oocytes and
      in corpora lutea (CL) during developmental and oestrous cycle changes. Grx was
      absent from the oocytes in the first days of postnatal life when marked oocyte
      degeneration takes place, but its presence was very conspicuous in the cytoplasm
      of oocytes in healthy and attretic follicles in rats from 10 days of age onward,
      independently of the day of oestrous cycle. Follicular cells were negative. Grx
      immunostaining in the CL was strong in infiltrating macrophages and in a
      population of steroidogenic cells that survived the apoptotic burst in regressing
      CL and in CL remnants, but was faint or absent in young CL of the current cycle
      and in CL during pseudopregnancy. Grx content and oxidoreductase activity in
      whole ovaries increased significantly during the phase transition from proestrous
      to oestrous along the cycle. These results support a role of Grx in the
      maintenance of functional oocytes and in luteal cells surviving the regression
      process, probably as a consequence of the demonstrated deglutathionylating
      function of this protein in an antioxidant and antiapoptotic context.

PMID- 15956335
TI  - Suppressor of cytokine signalling (SOCS) genes are expressed in the endometrium
      and regulated by conceptus signals during early pregnancy in the ewe.
AB  - It is established that the conceptus-endometrium dialogue involves cytokines,
      growth factors and hormones. Given the crucial functions of the suppressor of
      cytokine signaling (SOCS) family proteins in cytokine signalling, we analyzed the
      expression and the regulation of CIS and SOCSs 1-3 transcripts during early
      pregnancy in the ovine endometrium. An overall stimulation of the SOCS
      transcripts was described in the pregnant ewes with two specific patterns.
      Unilaterally pregnant ewes confirmed the conceptus-produced factors as regulators
      of the SOCSs 1-3 expression at day 16 of pregnancy. Intrauterine injection of
      recombinant ovine interferon tau (IFNtau) in cyclic ewes stimulated the
      expression of the SOCS mRNA with various potencies, therefore suggesting that the
      SOCS could take part in the negative regulation of the IFNtau signalling pathway.

PMID- 15956336
TI  - Disruption of the murine PIASx gene results in reduced testis weight.
AB  - PIASx belongs to the PIAS protein family, the members of which modulate
      activities of several transcription factors and act as E3 ligases in the
      sumoylation pathway. The PIASx gene is highly expressed in testis, suggesting a
      role in spermatogenesis. To investigate the function of PIASx in vivo, we have
      disrupted the PIASx gene in mice. Interestingly, the knockout mice were viable
      and fertile. Despite the normal fertility, the testis weight of the mutant
      animals was reduced and their number of apoptotic testicular cells was increased.
      Also, the sperm count of mutant mice tended to be reduced, but the quality of
      their sperm cells was normal. No significant changes were observed in the serum
      levels of LH and FSH or in the intratesticular testosterone concentration between
      the knockout animals and their wild-type littermates. Compensatory increases in
      other PIAS protein mRNAs were not observed in the knockout mice. These results
      imply that PIASx is required quantitatively rather than qualitatively for normal
      spermatogenesis.

PMID- 15956337
TI  - An arachidonic acid-preferring acyl-CoA synthetase is a hormone-dependent and
      obligatory protein in the signal transduction pathway of steroidogenic hormones.
AB  - We have described that, in adrenal and Leydig cells, the hormonal regulation of
      free arachidonic acid (AA) concentration is mediated by the concerted action of
      two enzymes: an acyl-CoA thioesterase (MTE-I or ARTISt) and an acyl-CoA
      synthetase (ACS4). In this study we analyzed the potential regulation of these
      proteins by hormonal action in steroidogenic cells. We demonstrated that ACS4 is
      rapidly induced by adrenocorticotropin (ACTH) and cAMP in Y1 adrenocortical
      cells. The hormone and its second messenger increased ACS4 protein levels in a
      time and concentration dependent way. Maximal concentration of ACTH (10 mIU/ml)
      produced a significant effect after 15 min of treatment and exerted the highest
      increase (3-fold) after 30 min. Moreover, (35)S-methionine incorporation showed
      that the increase in ACS4 protein levels is due to an increase in the de novo
      synthesis of the protein. On the contrary MTE-I protein levels in Y1 and MA-10
      cells did not change after steroidogenic stimuli. In contrast with the effect
      observed on protein levels, stimulation of both cell lines did not change ACS4
      RNA levels during the first hour of treatment, indicating that the effect of both
      stimuli is exerted at the level of ACS4 protein synthesis.StAR protein induction
      has a key role on the activation of steroidogenesis since this protein increases
      the rate of the limiting step of the whole process. In agreement with the fact
      that the inhibition of ACS4 activity by triacsin C blocks cAMP-stimulated
      progesterone production by MA-10 Leydig cells, here we demonstrated that ACS4
      inhibition also reduces StAR protein levels. Moreover, exogenous AA was able to
      overcome the effect of triacsin C on both events, StAR induction and
      steroidogenesis. These results were confirmed by experiments using ACS4-targeted
      siRNA which result in a reduction in both ACS4 and StAR protein levels. The
      concomitant decrease in steroid production was overcome by the addition of AA to
      the knocked-out cells. In summary, this study suggests that in adrenal and Leydig
      cells the hormonal action prompts the synthesis of a labile protein, ACS4, which
      activity is involved in the regulation of AA release and is essential for
      steroidogenesis and StAR protein induction.

PMID- 15956338
TI  - Differential effects of sex steroid hormones on the expression of multiple first
      exons including a novel first exon of prolactin receptor gene in the rat liver.
AB  - In addition to the known four alternative first exons E1(1), E1(2), E1(3) and
      E1(4) of the rat prolactin receptor (PRL-R) gene, a novel first exon, E1(5), was
      identified by cDNA cloning of the 5'-end region of PRL-R mRNA in the rat liver.
      Genomic fragments containing E1(5) and its 5'- or 3'-flanking regions were also
      cloned from rat kidney genomic DNA. A sequence search for E1(5) revealed that
      E1(5) is located 49 kb upstream of exon 2 of the PRL-R gene in rat chromosome
      2q16. RT-PCR analysis revealed that E1(5) was preferentially expressed in the
      liver, brain and kidney. Expression profiles of E1(2)-, E1(3)- and E1(5)-PRL-R
      mRNAs in the liver of male and female rats at 5 days of age and those at 8 weeks
      of age were examined by RT-PCR. The levels of E1(2)-PRL-R mRNA in the female rat
      increased remarkably in rats at 8 weeks of age compared with those at 5 days of
      age, and the levels of E1(5)-PRL-R mRNA in the male rat decreased markedly at 8
      weeks of age compared with those at 5 days of age. In the female rat, the levels
      of E1(2)-PRL-R mRNA at 8 weeks of age decreased with ovariectomy performed at 4
      weeks of age and recovered with the administration of beta-oestradiol. On the
      contrary, the levels of E1(5)-PRL-R mRNA increased with ovariectomy and decreased
      with the oestrogen treatment. In the male rat liver, the levels of E1(2)-PRL-R
      mRNA at 8 weeks of age increased strikingly with castration performed at 4 weeks
      of age and became undetectable with the administration of testosterone. The
      levels of E1(5)-PRL-R mRNA increased slightly with castration and were restored
      by testosterone treatment. Removal of gonadal tissues and sex steroid hormone
      treatment had no effect on the expression levels of E1(3)-PRL-R mRNA in both
      female and male rat livers. These results indicated that the expression of the
      PRL-R gene in the liver is regulated by the differential effects of sex steroid
      hormones on the transcription of the multiple first exons including the novel
      one.

PMID- 15956339
TI  - Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11 beta
      hydroxysteroid dehydrogenase type 1.
AB  - Two isozymes of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) interconvert
      active cortisol and inactive cortisone. 11 beta-HSD2 (renal) acts only as a
      dehydrogenase, converting cortisol to cortisone. 11 beta-HSD1 (liver) is a bi
      directional enzyme in cell homogenates, whereas in intact cells it typically
      displays oxo-reductase activity, generating cortisol from cortisone. We recently
      established that cortisone reductase deficiency is a digenic disease requiring
      mutations in both the gene encoding 11 beta-HSD1 and in the gene for a novel
      enzyme located within the lumen of the endoplasmic reticulum (ER), hexose-6
      phosphate dehydrogenase (H6PDH). This latter enzyme generates NADPH, the co
      factor required for oxo-reductase activity. Therefore, we hypothesized that H6PDH
      expression may be an important determinant of 11 beta-HSD1 oxo-reductase
      activity. Transient transfection of chinese hamster ovary (CHO) cells with 11
      beta-HSD1 resulted in the appearance of both oxo-reductase and dehydrogenase
      activities in intact cells. Co-transfection of 11 beta-HSD1 with H6PDH increased
      oxo-reductase activity whilst virtually eliminating dehydrogenase activity. In
      contrast, H6PDH had no effect on reaction direction of 11 beta-HSD2, nor did the
      cytosolic enzyme, glucose-6-phosphate dehydrogenase (G6PD) affect 11 beta-HSD1
      oxo-reductase activity. Conversely in HEK 293 cells stably transfected with 11
      beta-HSD1 cDNA, transfection of an H6PDH siRNA reduced 11 beta-HSD1 oxo-reductase
      activity whilst simultaneously increasing 11 beta-HSD1 dehydrogenase activity. In
      human omental preadipocytes obtained from 15 females of variable body mass index
      (BMI), H6PDH mRNA levels positively correlated with 11 beta-HSD1 oxo-reductase
      activity, independent of 11 beta-HSD1 mRNA levels. H6PDH expression increased 5.3
      fold across adipocyte differentiation (P < 0.05) and was associated with a switch
      from 11 beta-HSD1 dehydrogenase to oxo-reductase activity. In conclusion, H6PDH
      is a crucial determinant of 11 beta-HSD1 oxo-reductase activity in intact cells.
      Through its interaction with 11 beta-HSD1, H6PDH may represent a novel target in
      the pathogenesis and treatment of obesity.

PMID- 15956340
TI  - Interaction of insulin-like growth factor (IGF)-I and -II with IGF binding
      protein-2: mapping the binding surfaces by nuclear magnetic resonance.
AB  - The interaction of IGF binding protein-2 (IGFBP-2) with IGF-I and -II has been
      investigated in solution using nuclear magnetic resonance (NMR) spectroscopy.
      Chemical shift perturbations in 15N- and 2H/15N-labelled IGF-I or -II upon
      binding to unlabelled thioredoxin-tagged bovine IGFBP-2 (Trx(1-279)IGFBP-2) have
      been monitored to identify residues involved directly in the binding interaction
      as well as any affected by conformational changes associated with the
      interaction. A key step in obtaining high-quality spectra of the complexes was
      the use of transverse relaxation optimised spectroscopy (TROSY) methods with
      partially deuterated ligands. Indeed, because the effects of conformational
      averaging and aggregation are eliminated in IGF-I and -II bound to IGFBP-2, the
      spectra of the complexes are actually superior to those of the free ligands.
      Comparison of our results with the crystal structure of the complex between IGF-I
      and an N-terminal fragment of IGFBP-5 allowed identification of those residues
      perturbed by the C-domain of IGFBP-2. Other perturbations, such as those of Gly
      19 and Asp 20 of IGF-I (and the corresponding residues in IGF-II) - which are
      located in a reverse turn linking N-domain and C-domain interactive surfaces -
      are due to local conformational changes in the IGF-I and -II. Our results confirm
      that the C-domain of IGFBP-2 plays a key role in binding regions of IGF-I and -II
      that are also involved in binding to the type-1 IGF receptor and thereby blocking
      ligand binding to this receptor.

PMID- 15956341
TI  - IGF-I and vasoactive intestinal peptide (VIP) regulate cAMP-response element
      binding protein (CREB)-dependent transcription via the mitogen-activated protein
      kinase (MAPK) pathway in pituitary cells: requirement of Rap1.
AB  - In previous studies we demonstrated that vasoactive intestinal peptide (VIP)
      mediation, and interactions between mitogen-activated protein kinase (MAPK) and
      cAMP/protein kinase A (PKA) signaling pathways are implicated in insulin-like
      growth factor I (IGF-I)- and VIP-induced lactotroph proliferation. These facts
      led us to investigate the intracellular mechanisms involved in IGF-I- and VIP
      induced lactotroph proliferation. Exposure of cultured male rat pituitary cells
      to IGF-I (10(-7) M) or VIP (10(-7) M) stimulated the MAPK cascade. Studies in
      GH4C1 cells, with an expression vector for Rap1 GTPase-activating protein (Rap1
      GAP1), demonstrated reduced VIP-induced MAPK activation, indicating that VIP
      dependent activation of the extracellular signal-regulated kinase (ERK) pathway
      requires PKA-Rap1 signaling. IGF-I induced cAMP-response element (CRE)-binding
      protein (CREB) phosphorylation through the Ras-MAPK pathway, whereas VIP
      phosphorylated CREB directly via PKA. The mechanisms that regulate IGF-I-and VIP
      CREB-dependent gene transcription were examined using GH4C1 cells transiently
      transfected with a CRE reporter gene. IGF-I and VIP stimulation of CRE-mediated
      transcription required activation of both Ras-MAPK and cAMP/PKA signaling. This
      activation was blocked in the presence of Rap1 GAP1. In summary, we showed that
      IGF-I and VIP stimulated MAPK activity and the phosphorylation of CREB in
      pituitary cells. Furthermore, VIP-dependent activation of PKA-Rap1-ERK pathways
      mediated VIP and IGF-I effects on CREB-dependent transcription in GH4C1 cells.
      Thus, it is possible that VIP- and IGF-I-induced lactotroph proliferation may
      involve Rap1.

PMID- 15956342
TI  - Activation of the insulin-like growth factor binding protein-5 promoter by
      parathyroid hormone in osteosarcoma cells requires activation of an activated
      protein-2 element.
AB  - We have previously shown that parathyroid hormone (PTH) stimulates the expression
      of insulin-like growth factor binding protein-5 (IGFBP-5) transcript levels in
      the osteosarcoma cell-line, UMR106-01 cells. In the present study we examined the
      molecular basis for the PTH induction of IGFBP-5 mRNA in these cells. PTH had no
      effect on the half-life of the IGFBP-5 transcript but did stimulate the
      transactivation of the proximal 889 base pairs of the rat IGFBP 5' flanking
      region in a luciferase fusion construct, suggesting that PTH stimulates
      transcript levels through transcriptional mechanisms. Progressive 5' deletions to
      -59 base pairs of the proximal promoter region had no effect on PTH induction of
      transactivation, indicating that an element existed within the first -59 base
      pairs upstream of the transcription start site that was responsive to PTH. Within
      the -59 base pairs there are CCAAT/enhancer binding protein (C/EBP), E-box,
      nuclear factor-1 (NF-1) and activator protein-2 (AP-2) elements. Mutation of the
      C/EBP, E-box or NF-1 elements had no effect on the ability of PTH to induce the
      transactivation of the IGFBP-5 promoter. Mutation of the AP-2 element resulted in
      a 40% reduction of PTH-stimulated luciferase activity. When three tandem repeats
      of the AP-2 consensus sequence were fused to a luciferase reporter, PTH
      stimulated a 25% increase in reporter activity. Electrophoretic mobility shift
      assays using UMR106-01 cell nuclear extracts showed that PTH caused a prominent
      shifted band in a probe spanning the region containing all four elements. The
      shifted band was almost completely absent when the probe contained a mutated AP-2
      element. These results suggest that the AP-2 element functions in the PTH
      induction of IGFBP-5 gene expression.

PMID- 15956343
TI  - Signaling cross-talk between IGF-binding protein-3 and transforming growth factor
      (beta) in mesenchymal chondroprogenitor cell growth.
AB  - Cartilage formation is driven by mesenchymal chondroprogenitor cells (MCCs) that
      proliferate and differentiate into chondrocytes. The molecular mechanisms by
      which growth factors regulate MCC fate are not well defined. Insulin-like growth
      factor binding protein-3 (IGFBP-3) has intrinsic bioactivity that is independent
      of IGF binding. We previously reported that IGFBP-3 has IGF-independent
      antiproliferative and apoptotic effects in MCCs, and requires STAT-1 activation
      to mediate its apoptotic effect. Transforming growth factor-beta (TGF-beta) is a
      key chondroinductive growth factor. The objective of the study is to define the
      interactions between IGFBP-3 and TGF-beta in MCC growth and their intracellular
      signaling pathways. We used the RCJ3*1C5*18 mesenchymal chondrogenic cells that
      without biochemical or oncogenic transformation progress in culture from MCCs to
      differentiated chondrocytes. Cell proliferation was assessed in MCCs treated with
      IGFBP-3 or transfected with IGFBP-3, in the presence or absence of TGF-beta. To
      demonstrate that IGFBP-3 effects were IGF-independent an IGFBP-3 analog that
      lacks IGF binding was used (GGG-IGFBP-3). To determine the functional roles of
      the TGF-beta-mediated signaling and the STAT-1 pathway, cells were either stably
      transfected with a dominant negative TGF-beta type II receptor (MCC-DNTbetaRII)
      or treated with a STAT-1 morpholino antisense oligonucleotide. We found that in
      MCCs, TGF-beta antagonized the antiproliferative effect of IGFBP-3. IGFBP-3
      increased the cyclin-dependent kinase inhibitor p21 expression and this effect
      was abolished by TGF-beta. Furthermore, TGF-beta inhibited STAT-1 phosphorylation
      induced by IGFBP-3. Similarly to TGF-beta, STAT-1 antisense oligonucleotide
      inhibited the IGFBP-3 antiproliferative action. Although TGF-beta in MCC
      DNTbetaRII lacked Smad-mediated signaling, it persistently antagonized the IGFBP
      3 antiproliferative action. However, TGF-beta even in MCC-DNTbetaRII cells
      induced ERK1/2 phosphorylation, and treatment with MEK inhibitor, UO126,
      inhibited the antagonistic effects of TGF-beta on IGFBP-3. Furthermore, UO126
      blocked the TGF-beta inhibition of STAT-1 phosphorylation induced by IGFBP-3.
      Collectively, these results demonstrate cross-talk between the IGFBP-3-dependent
      STAT-1 signaling and the TGF-beta-dependent ERK pathway that regulates MCC
      proliferation.

PMID- 15956345
TI  - The secretin G-protein-coupled receptor family: teleost receptors.
AB  - Twenty-one members of the secretin family (family 2) of G-protein-coupled
      receptors (GPCRs) were identified via directed cloning and data-mining of the
      Fugu Genome Consortium database, representing the most comprehensive description
      of secretin GPCRs in a teleost fish to date. Duplicated genes were identified for
      many of the family members, namely the receptors for pituitary adenylate cyclase
      activating polypeptide (PACAP)/vasoactive intestinal peptide (VIP), calcitonin,
      calcitonin gene-related peptide (CGRP), growth hormone releasing hormone (GHRH),
      glucagon receptor/glucagon-like peptide (GLP) and parathyroid hormone-related
      peptide (PTHrP)/PTH. Mining of other teleost genomes (zebrafish and Tetraodon)
      revealed that the duplicated genes identified in the Takifugu genome were also
      present in these fish. Additional database searching of the Escherichia coli,
      yeast, Drosophila, Caenorhabditis elegans and Ciona genomes revealed that the
      family 2 of GPCRs were only present in the multicellular organisms. Orthologues
      of all the human secretin receptors were identified with the exception of
      secretin itself. Additional database searches in the Fugu Genome Consortium
      database also failed to reveal a secretin ligand and so it is hypothesised that
      both the receptor and the ligand evolved after the divergence of teleost/tetrapod
      lineages. Phylogenetic analysis at both the protein and the DNA level provided
      strong support for each of the individual receptor family groupings, but weak
      support between groups, making evolutionary inferences difficult. A more critical
      analysis of the PACAP/VIP receptor family confirmed previous hypotheses that the
      vasoactive intestinal peptide receptor (VPAC(1)R) gene is the ancestral form of
      the receptor.

PMID- 15956346
TI  - Five gonadotrophin-releasing hormone receptors in a teleost fish: isolation,
      tissue distribution and phylogenetic relationships.
AB  - Gonadotrophin-releasing hormone (GnRH) is the main neurohormone controlling
      gonadotrophin release in all vertebrates, and in teleost fish also of growth
      hormone and possibly of other adenohypophyseal hormones. Over 20 GnRHs have been
      identified in vertebrates and protochoordates and shown to bind cognate G-protein
      couple receptors (GnRHR). We have searched the puffer fish, Fugu rubripes, genome
      sequencing database, identified five GnRHR genes and proceeded to isolate the
      corresponding complementary DNAs in European sea bass, Dicentrachus labrax.
      Phylogenetic analysis clusters the European sea bass, puffer fish and all other
      vertebrate receptors into two main lineages corresponding to the mammalian type I
      and II receptors. The fish receptors could be subdivided in two GnRHR1 (A and B)
      and three GnRHR2 (A, B and C) subtypes. Amino acid sequence identity within
      receptor subtypes varies between 70 and 90% but only 50-55% among the two main
      lineages in fish. All European sea bass receptor mRNAs are expressed in the
      anterior and mid brain, and all but one are expressed in the pituitary gland.
      There is differential expression of the receptors in peripheral tissues related
      to reproduction (gonads), chemical senses (eye and olfactory epithelium) and
      osmoregulation (kidney and gill). This is the first report showing five GnRH
      receptors in a vertebrate species and the gene expression patterns support the
      concept that GnRH and GnRHRs play highly diverse functional roles in the
      regulation of cellular functions, besides the "classical" role of pituitary
      function regulation.

PMID- 15956344
TI  - Endocrinomic profile of neurointermediate lobe pituitary prohormone processing in
      PC1/3- and PC2-Null mice using SELDI-TOF mass spectrometry.
AB  - Pro-vasopressin and pro-oxytocin are prohormones processed in the
      neurointermediate lobe pituitary to form the biologically active peptide
      hormones, arginine vasopressin (AVP) and oxytocin. Neurointermediate lobe
      pituitaries from normal (+/+), heterozygous (+/-), PC2-Null (-/-), PC1/3-Null and
      oxytocin-Null mice were analyzed by SELDI-TOF mass spectroscopy for the peptide
      hormone products, AVP, oxytocin and neurophysin I and II. Molecular ion species
      with masses characteristic of oxytocin, AVP, neurophysin I and II, i.e. 1009.41,
      1084.5, 9677 and 9679 daltons respectively, were identified in all but the
      oxytocin-Null mice by comparison with synthetic standards or by C-terminal
      sequence analysis. Other ion species were found specifically in PC2-Null,
      heterozygote or normal mice. The results indicate that, in mice, both PC1/3 or
      PC2 enzyme activity are capable, but not required to correctly process pro
      vasopressin or pro-oxytocin to their constituent active peptide hormones.

PMID- 15956347
TI  - Molecular characterization of three forms of putative membrane-bound progestin
      receptors and their tissue-distribution in channel catfish, Ictalurus punctatus.
AB  - Membrane-bound progestin receptors (mPR) were recently cloned and characterized
      as a new class of steroid receptors that transduce cell-signals through
      alteration of MAP kinase- and cAMP-dependent pathways. To further develop our
      understanding of this new class of steroid receptors, we characterized the cDNAs
      and genes of thealpha, beta and gamma forms of the channel catfish mPRs (IpmPR).
      The predicted alpha and beta proteins have 49% sequence identity, whereas they
      only have 30% and 27% identities, respectively, with the gamma form. Furthermore,
      IpmPRalpha and IpmPRbeta genes have similar structures featuring intronless
      coding regions, while IpmPRgamma gene is composed of 8 exons and 7 introns. The
      5'-flanking region of each IpmPR gene differs, but each contains putative
      transcriptional regulatory elements of factors known to influence reproductive
      physiology and endocrine disruption, for example, responsive elements for cAMP
      and steroids and the recognition sites for steroidogenic factor-1 and for the
      aryl hydrocarbon receptor. The IpmPRalpha gene was detected in all the tissues
      tested with relatively greater expression in brain, pituitary, muscle and testis.
      The expression of IpmPRbeta was much lower than that of IpmPRalpha and the
      transcript was predominantly observed in brain, pituitary, ovary and testis. In
      contrast, the IpmPRgamma transcript was mainly detected in gill, ventral aorta,
      intestine, and trunk kidney. In conclusion, all the structural features of the
      IpmPRs strongly suggest that the closely related alpha and beta forms are
      distantly related to the gamma form. Additionally, regulatory features of the 5'
      flanking regions and the differences in tissue-specific expression of each IpmPR
      gene suggest that they are involved in different endocrine functions in catfish.

PMID- 15956348
TI  - Molecular cloning and functional characterization of a type-I neurotensin
      receptor (NTR) and a novel NTR from the bullfrog brain.
AB  - Neurotensin (NT) is a tridecapeptide that functions as a neurotransmitter and
      neuromodulator in the nervous system. To date, three different types of NT
      receptor (NTR), NTR1, NTR2 and NTR3, have been identified only in mammalian
      species. In the present study we isolated the cDNAs for an NTR1 and a novel NTR
      in the bullfrog brain, designated bfNTR1 and bfNTR4 respectively. bfNTR1 and
      bfNTR4 encode 422- and 399-amino acid residue proteins respectively. bfNTR1 has a
      64% amino acid identity with mammalian NTR1, and 34-37% identity with mammalian
      NTR2. bfNTR4 exhibits 43% and 45-47% identity with mammalian NTR1 and NTR2
      respectively. Both receptors are mainly expressed in the brain and pituitary.
      bfNTR1 triggers both CRE-luc, a protein kinase A (PKA)-specific reporter, and c
      fos-luc, a PKC-specific reporter, activities, indicating that bfNTR1 can activate
      PKA- and PKC-linked signaling pathways. However, bfNTR4 appears to be
      preferentially coupled to the PKA-linked pathway as it induces a higher CRE-luc
      activity than c-fos-luc activity. bfNTRs exhibit different pharmacological
      properties as compared with mammalian NTRs. Mammalian NTR1 but not NTR2 responds
      to NT, whereas both bfNTR1 and bfNTR4 show a high sensitivity to NT. SR 48692 and
      SR 142948A, antagonists for mammalian NTR1 but agonists for mammalian NTR2,
      function as antagonists for both bfNTR1 and bfNTR4. In conclusion, this report
      provides the first molecular, pharmacological and functional characterization of
      two NTRs in a non-mammalian vertebrate. These data should help to elucidate the
      phylogenetic history of the G protein-coupled NTRs in the vertebrate lineage as
      well as the structural features that determine their pharmacological properties.

PMID- 15956349
TI  - Cloning, heterologous expression and pharmacological characterization of a kappa
      opioid receptor from the brain of the rough-skinned newt, Taricha granulosa.
AB  - A full-length cDNA that encodes a kappa (kappa) opioid receptor has been isolated
      from the brain of a urodele amphibian, the rough-skinned newt Taricha granulosa.
      The deduced protein contains 385 amino acids and possesses features commonly
      attributed to G protein-coupled receptors, such as seven putative transmembrane
      domains. The newt kappa receptor has 75% sequence identity to kappa opioid
      receptors cloned from mammals, and 66% sequence identity to the kappa opioid
      receptor reported for the zebrafish, with the greatest divergence in the
      extracellular N-terminus, the second and third extracellular loops and the
      intracellular C-terminus. Membranes isolated from COS-7 cells expressing the newt
      kappa receptor possessed a single, high-affinity (Kd = 1.5 nM) binding site for
      the kappa-selective agonist U69593. In competition binding assays, the expressed
      newt kappa receptor displayed high affinity for the kappa-selective agonists
      GR89696, dynorphin A(1-13), U69593, U50488 and BRL52537, as well as the kappa
      selective antagonist nor-binaltorphimine and the non-selective antagonist
      naloxone. Rank order potencies and affinity constants were similar in competition
      binding studies that used either whole brain homogenates or membranes isolated
      from COS-7 cells expressing the newt kappa receptor. The expressed receptor
      displayed essentially no affinity for the delta-selective agonist DPDPE ([d
      penicillamine, d-penicillamine]enkephalin), but showed moderate affinity for the
      mu-selective agonist DAMGO ([d-Ala-MePhe, Gly-ol]enkephalin) and moderately high
      affinity for nociceptin (orphanin FQ), the endogenous ligand for the opioid
      receptor-like (ORL)1 receptor. These findings support the conclusions that a gene
      for the kappa opioid receptor is expressed in amphibians and that the
      pharmacology of the newt kappa receptor closely matches mammalian kappa opioid
      receptors. However, the functional dichotomy between the classic opioid receptors
      (kappa, delta, mu) and ORL1 appears less strict in amphibians than in mammals.

PMID- 15956350
TI  - Expression of prolactin-releasing peptide and prolactin in the euryhaline
      mudskippers (Periophthalmus modestus): prolactin-releasing peptide as a primary
      regulator of prolactin.
AB  - Prolactin (PRL)-releasing peptide (PrRP) is a strong candidate stimulator of
      pituitary PRL transcription and secretion in teleosts. However, the role in
      control of extrapituitary PRL expression is unclear even in mammals. To study the
      possible presence of PrRP-PRL axes not only in the brain-pituitary but also in
      peripheral organs, the expression patterns of PrRP, PRL and growth hormone (GH)
      were characterized in amphibious euryhaline mudskippers (Periophthalmus
      modestus). PrRP mRNA is abundantly expressed not only in the brain but also in
      the liver, gut and ovary, while less abundant expression was also detected in the
      skin and kidney. Corresponding to the distribution of PrRP mRNA, PRL mRNA was
      also detectable in these organs. During adaptation to different environments, the
      changes in mRNA levels of PrRP paralleled those in PRL in the brain-pituitary,
      liver and gut in an organ-specific manner. Brain PrRP mRNA and the pituitary PRL
      mRNA increased under freshwater and terrestrial conditions (P < 0.05); expression
      of PrRP and PRL in the gut of freshwater fish was higher (P < 0.05) than those in
      sea-water fish although there were no changes in fish kept out of water; no
      significant change was seen in the liver. Expressions of GH were not correlated
      with PrRP. In the gut, PrRP and PRL appear to be co-localized in the mucosal
      layer, especially in the mucous cells. Thus, PrRP may also be a local modulator
      of extrapituitary PRL expression and the PrRP-PRL axes in various organs may play
      an organ-specific role during environmental adaptation.

PMID- 15956351
TI  - TRAP220 is modulated by the antineoplastic agent 6-Mercaptopurine, and mediates
      the activation of the NR4A subgroup of nuclear receptors.
AB  - The NR4A1-3 (Nur77, NURR1 and NOR-1) subfamily of nuclear hormone receptors (NRs)
      has been implicated in Parkinson's disease, schizophrenia, manic depression,
      atherogenesis, Alzheimer's disease, rheumatoid arthritis, cancer and apoptosis.
      This has driven investigations into the mechanism of action, and the
      identification of small molecule regulators, that may provide the platform for
      pharmaceutical and therapeutic exploitation. Recently, we found that the purine
      antimetabolite 6-Mercaptopurine (6-MP), which is widely used as an anti
      neoplastic and anti-inflammatory drug, modulated the NR4A1-3 subfamily.
      Interestingly, the agonist-mediated activation did not involve modulation of
      primary coactivators' (e.g. p300 and SRC-2/GRIP-1) activity and/or recruitment.
      However, the role of the subsequently recruited coactivators, for example CARM-1
      and TRAP220, in 6-MP-mediated activation of the NR4A1-3 subfamily remains
      obscure. In this study we demonstrate that 6-MP modulates the activity of the
      coactivator TRAP220 in a dose-dependent manner. Moreover, we demonstrate that
      TRAP220 potentiates NOR-1-mediated transactivation, and interacts with the NR4A1
      3 subgroup in an AF-1-dependent manner in a cellular context. The region of
      TRAP220 that mediated 6-MP activation and NR4A interaction was delimited to amino
      acids 1-800, and operates independently of the critical PKC and PKA
      phosphorylation sites. Interestingly, TRAP220 expression does not increase the
      relative induction by 6-MP, however the absolute level of NOR-1-mediated trans
      activation is increased. This study demonstrates that 6-MP modulates the activity
      of the NR4A subgroup, and the coactivator TRAP220.

PMID- 15956352
TI  - Decreased expression of retinoid nuclear receptor (RAR alpha and RAR gamma) mRNA
      determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells
      of hypothyroid patients.
AB  - In vivo assessment of the cellular impact of thyroid hormones on target tissues
      might be of help for physiological studies and to evaluate the consequences of
      various diseases of the thyroid gland in humans. Given the tenuous relationship
      between retinoid and tri-iodothyronine (T3) status and that retinoids have also
      intracellular roles, the aim of this study was to determine the effect of
      hypothyroidism on the expression of T3 nuclear receptors (TR) and retinoic acid
      nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC).
      Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid
      (TR alpha and TR beta) and retinoid (RAR alpha, RAR gamma, and RXR alpha) nuclear
      receptors in PBMC of euthyroid (n = 22) compared with hypothyroid (n = 22)
      subjects. Classical plasma parameters (free T3 (FT3), free thyroxine (T4) (FT4),
      thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP)
      and transthyretin (TTR)) were also measured. In hypothyroid subjects, the
      concentration of TSH was elevated, and dramatically low T3 and T4 concentrations
      were associated with a decrease in the expression of TR beta. Expression of RAR
      alpha and RAR gamma significantly decreased in hypothyroid versus control
      subjects, while an increased concentration of ROH was emphasised by
      hypothyroidism. These results first indicated that primary hypothyroidism induces
      hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted
      by the plasma ROH level. Further investigations will be necessary to evaluate
      these parameters in very small changes in thyroid hormone production such as mild
      (subclinical) hypothyroidism.

PMID- 15956353
TI  - A haplotype of the CYP27B1 promoter is associated with autoimmune Addison's
      disease but not with Graves' disease in a UK population.
AB  - Previous studies have suggested an association between alleles of the CYP27B1 (1
      alpha hydroxylase) gene and autoimmune conditions. We have examined three single
      nucleotide polymorphisms (SNPs) that are located in the 5' region and promoter of
      the CYP27B1 gene for association in a cohort of Graves' disease and autoimmune
      Addison's disease subjects from the UK. Genomic DNA samples from white patients
      with autoimmune Addison's disease (n = 104) and healthy controls (n = 464) were
      genotyped by PCR-RFLP analysis for the SNPs at positions -1260 and -1077 5' of
      the coding CYP27B1 sequences. The -1260 SNP was also examined in a cohort of
      patients with Graves' disease (n = 446). Chi 2 testing of contingency tables was
      used to determine the significance of genotypes and alleles. Haplotype
      frequencies and linkage disequilibrium measures were estimated using the UNPHASED
      and HAPLOVIEW packages. Alleles at the three CYP27B1 markers were in tight
      linkage disequilibrium with each other and all showed association with autoimmune
      Addison's disease. The maximum evidence for association was with the -1260 C
      allele (76.0% in Addison's subjects versus 64.9% in controls; P = 0.003; odds
      ratio 1.71 (5-95% confidence intervals, 1.20-2.44). A global test of significance
      for the common -1918 T, -1260 C and -1077 G haplotype was significant in
      Addison's subjects compared with controls (P = 0.01). In contrast, there was no
      association of alleles at the -1260 SNP with Graves' disease. We are able to
      confirm that a CYP27B1 promoter allele is associated with autoimmune Addison's
      disease, and extend this finding to include an associated promoter haplotype.

PMID- 15956354
TI  - Expression of recombinant membrane-bound type I iodothyronine deiodinase in
      yeast.
AB  - The bioactivity of thyroid hormone is determined to a large extent by the
      monodeiodination of the prohormone thyroxine (T4) by the hepatic selenoenzyme
      type I iodothyronine deiodinase (D1), i.e. by outer ring deiodination (ORD) to
      the active hormone triiodothyronine (T3) or by inner ring deiodination (IRD) to
      the inactive metabolite reverse T3 (rT3). Since D1 is a membrane-bound protein
      with an N-terminal membrane-spanning domain, the enzyme is very difficult to
      purify in an active state. This study was undertaken in order to develop a
      heterologous (over)-expression system that would eventually allow the production
      of large amounts of purified active D1 protein. We have expressed a mutant rat D1
      protein, in which the selenocysteine residue in the core catalytic center was
      replaced by cysteine (D1 Cys) in yeast cells (Saccharomyces cerevisiae). After
      yeast cell fractionation, kinetic analysis was performed with dithiothreitol as
      reducing cofactor. ORD activity was associated with membrane fractions, while no
      activity could be detected in the cytosolic fraction. The D1 Cys protein
      displayed a tenfold increase in Km (2 microM) for rT3 as compared with native D1
      protein in rat liver microsomes. The D1 protein content is about 65 pmol/mg
      microsomal protein, as compared with about 3 pmol/mg in rat liver microsomal
      fraction. SDS-PAGE analysis of N-bromoacetyl-[125I]T3 affinity-labeled D1 protein
      showed several labeled protein isoforms with apparent molecular masses between 27
      and 32 kDa. Immunoblot analysis with a specific D1 antiserum confirmed the
      observed D1 protein heterogeneity. Site-directed mutagenesis of several potential
      N-linked glycosylation sites, phosphorylation sites and a unique myristoylation
      site established that D1 heterogeneity is not caused by N-linked glycosylation,
      but probably by a combination of O-linked glycosylation and phosphorylation.
      Deletion of the endoplasmic reticulum (ER)-signal sequence and the membrane
      spanning domain (amino acid residue 2-35), did not result in the production of a
      soluble D1 enzyme. Although this mutated D1 protein is inactive, the fact that it
      is still membrane bound indicates the existence of additional membrane attachment
      site(s) or membrane-spanning domains. Overall, our studies indicate that yeast
      cells provide a useful system for the expression of relatively high levels of D1
      protein which could be used for further structure-function analysis.

PMID- 15956355
TI  - Identification of a heterodimer-specific epitope present in human chorionic
      gonadotrophin (hCG) using a monoclonal antibody that can distinguish between hCG
      and human LH.
AB  - Human chorionic gonadotrophin (hCG) is secreted during early pregnancy and is
      required for implantation and maintenance of the pregnancy. Active or passive
      immunoneutralization of hCG results in termination of pregnancy and this forms
      the basis of the hCG-based female contraceptive vaccine. However, the beta
      subunit of hCG possesses 85% sequence homology with the first 114 amino acids of
      the beta subunit of pituitary human LH (hLH), which is required for ovulation and
      maintenance of the corpus luteum function during the menstrual cycle.
      Immunization against hCG or its beta subunit leads to generation of antibodies
      that can neutralize hLH due to many shared epitopes and hence may cause abnormal
      menstrual cycles. Therefore, it is essential to identify epitopes that are
      different in the two hormones. In the present study, we report a monoclonal
      antibody (MAb) specific for hCG that shows no binding to the isolated subunits.
      Interestingly, the MAb also does not bind hLH at all. The epitope mapping
      analysis revealed that this antibody recognizes a unique discontinuous epitope
      present only in the heterodimeric hCG and is distinct from the unique C-terminal
      extension of hCG beta that is absent in hLH beta. The MAb, either as IgG or its
      recombinant single-chain variable region fragment, inhibited the response to hCG,
      but not to hLH. Thus, the epitope recognized by this MAb is an ideal candidate
      antigen for immunocontraception.

PMID- 15956356
TI  - Gene expression profiling of bovine endometrium during the oestrous cycle:
      detection of molecular pathways involved in functional changes.
AB  - The endometrium plays a central role among the reproductive tissues in the
      context of early embryo-maternal communication and pregnancy. It undergoes
      typical changes during the sexual/oestrous cycle, which are regulated by the
      ovarian hormones progesterone and oestrogen. To identify the underlying molecular
      mechanisms we have performed the first holistic screen of transcriptome changes
      in bovine intercaruncular endometrium at two stages of the cycle--end of day 0
      (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A
      combination of subtracted cDNA libraries and cDNA array hybridisation revealed
      133 genes showing at least a 2-fold change of their mRNA abundance, 65 with
      higher levels at oestrus and 68 at dioestrus. Interestingly, genes were
      identified which showed differential expression between different uterine
      sections as well. The most prominent example was the UTMP (uterine milk protein)
      mRNA, which was markedly upregulated in the cranial part of the ipsilateral
      uterine horn at oestrus. A Gene Ontology classification of the genes with known
      function characterised the oestrus time by elevated expression of genes, for
      example related to cell adhesion, cell motility and extracellular matrix and the
      dioestrus time by higher expression of mRNAs encoding for a variety of enzymes
      and transport proteins, in particular ion channels. Searching in pathway
      databases and literature data-mining revealed physiological processes and
      signalling cascades, e.g. the transforming growth factor-beta signalling pathway
      and retinoic acid signalling, which are potentially involved in the regulation of
      changes of the endometrium during the oestrous cycle.

PMID- 15956357
TI  - Multidrug-resistant tuberculosis (MDR-TB): epidemiology, prevention and
      treatment.
AB  - Multidrug-resistant tuberculosis (MDR-TB) is an increasing global problem, with
      most cases arising from a mixture of physician error and patient non-compliance
      during treatment of susceptible TB. The extent and burden of MDR-TB varies
      significantly from country to country and region to region. As with TB itself,
      the overwhelming burden of MDR-TB is in high-burden resource-poor countries. The
      diagnosis depends on confirming the drug susceptibility pattern of isolated
      organisms, which is often only possible in resource-rich settings. There should
      be a strong suspicion of drug resistance, including MDR-TB, in persons with a
      history of prior treatment or in treatment failure cases. Treatment in developed
      countries is expensive and involves an individualized regimen based on drug
      susceptibility data and use of reserve drugs. In resource-poor settings a WHO
      retreatment regimen may be used, but increasingly the move is to a directly
      observed treatment based 'DOTS-plus' regimen in a supported national TB
      programme. However, even where such treatment is given, the outcome for patients
      is significantly worse than that for fully susceptible TB and has a much higher
      cost.

PMID- 15956359
TI  - Crossroads of estrogen receptor and NF-kappaB signaling.
AB  - Cellular homeostasis in higher organisms is maintained by balancing cell growth,
      differentiation, and death. Two important systems that transmit extracellular
      signals into the machinery of the cell nucleus are the signaling pathways that
      activate nuclear factor kappaB (NF-kappaB) and estrogen receptor (ER). These two
      transcription factors induce expression of genes that control cell fates,
      including proliferation and cell death (apoptosis). However, ER has anti
      inflammatory effects, whereas activated NF-kappaB initiates and maintains
      cellular inflammatory responses. Recent investigations elucidated a nonclassical
      and nongenomic effect of ER: inhibition of NF-kappaB activation and the
      inflammatory response. In breast cancer, antiestrogen therapy might cause
      reactivation of NF-kappaB, potentially rerouting a proliferative signal to breast
      cancer cells and contributing to hormone resistance. Thus, ER ligands that
      selectively block NF-kappaB activation could provide specific potential therapy
      for hormone-resistant ER-positive breast cancers.

PMID- 15956360
TI  - Rapid, estrogen receptor-mediated signaling: why is the endothelium so special?
AB  - Classical, ligand-activated genomic effects of estrogen receptors (ERs) were once
      thought to mediate all estrogen responses. It is now accepted that rapid,
      nongenomic responses, mediated by ER-containing membrane complexes, occur in many
      tissues. The endothelium is a major target of such responses and is the critical
      regulatory tissue that, when normally functional, determines a state of "vascular
      health." When dysfunctional, the phenotypic and functional alterations result in
      vascular pathology, the most common form of which is atherosclerosis. Nitric
      oxide (NO) is a vascular protective substance generated by endothelial NO
      synthase (eNOS) in endothelial cells. The engagement of membrane ERs by 17beta
      estradiol (E2) is a potent stimulus to eNOS activation and NO release. Here, we
      describe the multimolecular components of ER-containing membrane complex assembly
      and the mechanisms directing ER targeting to caveolae microdomains in the plasma
      membrane. We discuss the possibility that various ERalpha splice forms, expressed
      in endothelial cells, may be particularly efficient signal transducers and may
      use classical receptor domains for membrane targeting and insertion. Finally, we
      discuss the biomedical ramifications of ER-mediated endothelial activation,
      including the controversies surrounding hormone replacement therapy and
      cardiovascular disease.

PMID- 15956361
TI  - Human papillomaviruses and cell signaling.
AB  - Human papillomaviruses cause cancer of the stratified epithelium, and the
      incidence of infection with these viruses in the genital tract is high. The
      alterations in the biology of normal epithelial cells that lead to malignancy are
      a consequence of the activity of certain viral proteins, whose function is to
      create an environment conducive to the replication of the viral genome through
      inhibition of epithelial cell differentiation and stimulation of proliferation.

PMID- 15956362
TI  - Practical methods using boronic acid compounds for identification of class C beta
      lactamase-producing Klebsiella pneumoniae and Escherichia coli.
AB  - Detection of the resistance mediated by class C beta-lactamases remains a
      challenging issue, considering that transferable plasmid-mediated class C beta
      lactamases are of worldwide concern. Methods for the identification of strains
      that produce extended-spectrum beta-lactamases (ESBLs) or metallo-beta-lactamases
      (MBLs) have been developed and applied for routine use in clinical microbiology
      laboratories, but no practical methods for identification of plasmid-mediated
      class C producers have been established to date. We therefore developed three
      simple methods for clinical microbiology laboratories that allow identification
      of plasmid-mediated class C beta-lactamase-producing bacteria using a boronic
      acid derivative, 3-aminophenylboronic acid (APB), one of the specific inhibitors
      of class C beta-lactamases. Detection by the disk potentiation test was based on
      the enlargement of the growth-inhibitory zone diameter (by greater than or equal
      to 5 mm) around a Kirby-Bauer disk containing a ceftazidime (CAZ) or a cefotaxime
      (CTX) disk in combination with APB. In a double-disk synergy test, the
      discernible expansion of the growth-inhibitory zone around the CAZ or the CTX
      disk toward a disk containing APB was indicative of class C beta-lactamase
      production. A greater than or equal to eightfold decrease in the MIC of CAZ or
      CTX in the presence of APB was the criterion for detection in the microdilution
      test. By using these methods, Escherichia coli and Klebsiella pneumoniae isolates
      producing plasmid-mediated class C beta-lactamases, ACT-1, CMY-2, CMY-9, FOX-5,
      LAT-1, and MOX-1, were successfully distinguished from those producing other
      classes of beta-lactamases, such as ESBLs and MBLs. These methods will provide
      useful information needed for targeted antimicrobial therapy and better infection
      control.

PMID- 15956363
TI  - Pandemic serovars (O3:K6 and O4:K68) of Vibrio parahaemolyticus associated with
      diarrhea in Mozambique: spread of the pandemic into the African continent.
AB  - Forty-two episodes of Vibrio parahaemolyticus infections were detected in Beira,
      Mozambique, from January to May 2004. The majority of the isolates (81%) belonged
      to the pandemic serovars (O3:K6 and O4:K68) of V. parahaemolyticus. The pandemic
      serovars were positive by group-specific PCR (GS-PCR) and a PCR specific for open
      reading frame ORF8 (ORF8-PCR), which are molecular markers of the pandemic clone,
      and were positive for tdh but negative for trh. The remaining 19% of the strains
      also possessed the tdh gene but were GS-PCR and ORF8-PCR negative and did not
      belong to the pandemic serovars. Patients with V. parahaemolyticus infection were
      older (mean age, 27 years) than patients infected by other diarrheal agents (mean
      age, 21 years). Ten percent of diarrhea patients from whom no V. parahaemolyticus
      was cultured were severely dehydrated, but none of the V. parahaemolyticus cases
      were severely dehydrated. This is the first report of the isolation of pandemic
      strains of V. parahaemolyticus in sub-Saharan Africa and clearly indicates that
      the pandemic of V. parahaemolyticus has spread into the African continent.

PMID- 15956364
TI  - Comparison of the COBAS AMPLICOR MTB and BDProbeTec ET assays for detection of
      Mycobacterium tuberculosis in respiratory specimens.
AB  - The performances of the BDProbeTec ET (Becton Dickinson) and COBAS AMPLICOR MTB
      (Roche) were retrospectively evaluated for detecting Mycobacterium tuberculosis
      complex in various respiratory specimens. The BACTEC and MGIT liquid culture
      system (Becton Dickinson) was used as a reference method. A total of 824
      respiratory specimens, comprised of sputa, bronchoalveolar lavage fluid, and
      bronchial and tracheal aspirates from 580 patients, were evaluated. Out of 824
      clinical specimens, 109 specimens from 43 patients were culture positive for M.
      tuberculosis. Of these 109 specimens, 67 were smear positive, 85 were positive by
      the COBAS AMPLICOR MTB test, and 94 were positive by the BDProbeTec ET. Of the
      715 culture-negative specimens, 17 were positive by the auramine staining, 11
      were positive by the COBAS AMPLICOR MTB test, and 12 were positive by the
      BDProbeTec ET. After discrepancy analysis and review of the patients' clinical
      data, 130 specimens from 50 patients were considered "true-positive" specimens.
      This resulted in the following sensitivities: microscopy, 61.5%; COBAS AMPLICOR
      MTB test, 78.0%; and BDProbeTec ET, 86.2%. The specificities of each system,
      based on the clinical diagnosis, were 99.7% for microscopy, 99.9% for the COBAS
      AMPLICOR MTB test, and 99.9% for the BDProbeTec ET. The data presented represent
      a considerable number of specimens evaluated with a considerable number of
      culture- and auramine-positive and culture-positive and auramine-negative results
      and therefore give a realistic view of how the data should be interpreted in a
      daily routine situation. Specifically, the data with regard to the culture
      positive and auramine-negative specimens are useful, because in a routine
      situation, auramine-negative specimens are sometimes accepted, on clinical
      indications, to be analyzed by an amplification method.

PMID- 15956365
TI  - Use of the INNO-LiPA-MYCOBACTERIA assay (version 2) for identification of
      Mycobacterium avium-Mycobacterium intracellulare-Mycobacterium scrofulaceum
      complex isolates.
AB  - Using INNO-LiPA-MYCOBACTERIA (Lipav1; Innogenetics) and the AccuProbe (Gen-Probe
      Inc./bioMerieux) techniques, 35 Mycobacterium avium-Mycobacterium intracellulare
      Mycobacterium scrofulaceum (MAC/MAIS) complex strains were identified between
      January 2000 and December 2002. Thirty-four of 35 isolates were positive only for
      the MAIS complex probe by Lipav1 and were further analyzed by INNO-LiPA
      MYCOBACTERIA version 2 (Lipav2), hsp65 PCR restriction pattern analysis (PRA),
      and ribosomal internal transcribed spacer (ITS), hsp65, and 16S rRNA sequences.
      Lipav2 identified 14 of 34 strains at the species level, including 11 isolates
      positive for the newly specific MAC sequevar Mac-A probe (MIN-2 probe). Ten of
      these 11 isolates corresponded to sequevar Mac-A, which was recently defined as
      Mycobacterium chimerae sp. nov. Among the last 20 of the 34 MAIS isolates, 17 (by
      hsp65 PRA) and 18 (by hsp65 sequence) were characterized as M. avium. Ten of the
      20 were identified as Mac-U sequevar. All these 20 isolates were identified as M.
      intracellulare by 16S rRNA sequence except one isolate identified as
      Mycobacterium paraffinicum by 16S rRNA and ITS sequencing. One isolate out of 35
      isolates that was positive for M. avium by AccuProbe and that was Mycobacterium
      genus probe positive and MAIS probe negative by Lipav1 and Lipav2 might be
      considered a new species. In conclusion, the new INNO-LiPA-MYCOBACTERIA allowed
      the identification of 40% of the previously unidentified MAIS isolates at the
      species level. The results of the Lipav2 assay on the MAIS isolates confirm the
      great heterogeneity of this group and suggest the use of hsp65 or ITS sequencing
      for precise identification of such isolates.

PMID- 15956366
TI  - First reported outbreak of diarrhea due to adenovirus infection in a hematology
      unit for adults.
AB  - Numerous outbreaks of adenovirus infection from different types of health care
      settings, except a hematology unit, have been reported. This is the first report
      describing an outbreak of adenovirus infection causing diarrhea among adult
      hematopoietic stem cell transplant recipients. Six of 21 patients from the
      outbreak cohort were affected with diarrhea. Electron microscopy, cell culture,
      and direct DNA sequencing of amplicons generated from stool and blood samples
      were used to investigate this outbreak. Electron microscopy and cell culture
      detected adenovirus in stools from symptomatic patients. DNA sequencing of
      amplicons generated from stool samples confirmed nosocomial transmission of
      infection from a single index case. The outbreak strain was also detected in
      plasma of four of these patients, suggesting systemic infection. The outbreak
      strain was identified as type 12. Standard infection control measures were
      effective to control this outbreak.

PMID- 15956367
TI  - Identification, molecular characterization, and experimental transmission of a
      new hemoplasma isolate from a cat with hemolytic anemia in Switzerland.
AB  - Recently, there has been a growing interest in hemotropic mycoplasmal species
      (also known as the hemoplasmas), the causative agents of infectious anemia in
      several mammalian species. In felids, two different hemoplasma species have been
      recognized: Mycoplasma haemofelis (formerly Haemobartonella felis) and
      "Candidatus Mycoplasma haemominutum." Recently developed molecular methods have
      allowed sensitive and specific identification and quantification of these agents
      in feline blood samples. In applying these methods to an epidemiological study
      surveying the Swiss pet cat population for hemoplasma infection, we discovered a
      third novel and unique feline hemoplasma isolate in a blood sample collected from
      a cat that had exhibited clinical signs of severe hemolytic anemia. This agent
      was readily transmitted via intravenous inoculation to two specific-pathogen-free
      cats. One of these cats was immunocompromised by the administration of
      methylprednisolone acetate prior to inoculation, and this cat developed severe
      anemia. The other immunocompetent cat showed a moderate decrease in packed cell
      volume. Additionally, an increase in red blood cell osmotic fragility was
      observed. Sequencing of the entire 16S rRNA gene of the new hemoplasma isolate
      and phylogenetic analysis showed that the isolate was most closely related to two
      rodent hemotropic mycoplasmal species, M. coccoides and M. haemomuris. A
      quantitative real-time PCR assay specific for this newly discovered agent was
      developed, which will be a prerequisite for the diagnosis of infections with the
      new hemoplasma isolate.

PMID- 15956368
TI  - Flow cytometry susceptibility testing for the antifungal caspofungin.
AB  - Rapid antifungal susceptibility testing for the antifungal agent caspofungin can
      be performed using flow cytometry (FC). An FC procedure using acridine orange
      provided minimum inhibitory concentration (MIC) results within 7 to 9 h which
      were compared with results obtained using the NCCLS M27-A2 protocol. To evaluate
      the consistency of this method, susceptibility testing using caspofungin was
      performed using 73 isolates of eight different species of Candida from various
      clinical samples in Central California. Macrotiter or microdilution tests were
      performed according to the NCCLS M27-A2 protocol, and the MICs were compared to
      those provided by our flow cytometry method. All isolates tested had results
      within the sensitive interpretive category, and 90% of the results compared
      within 1 dilution, showing excellent agreement between the methods. The MIC at
      which 50% of the isolates tested were inhibited (MIC50) and the MIC90 of
      caspofungin for all eight Candida species were within 1 dilution. This flow
      cytometer 7-h protocol for testing the antifungal susceptibility of Candida
      species to caspofungin provided results equivalent to those obtained with the M27
      A2 protocol.

PMID- 15956369
TI  - Comparison of qualitative (COBAS AMPLICOR HCV 2.0 versus VERSANT HCV RNA) and
      quantitative (COBAS AMPLICOR HCV monitor 2.0 versus VERSANT HCV RNA 3.0) assays
      for hepatitis C virus (HCV) RNA detection and quantification: impact on diagnosis
      and treatment of HCV infections.
AB  - Quantitative measurements of serum hepatitis C virus (HCV) RNA are becoming
      increasingly important in the management of HCV-infected patients. Here we
      compared two quantitative assays, the COBAS AMPLICOR HCV Monitor 2.0 assay (Roche
      Diagnostics) and the branched DNA-based VERSANT HCV RNA 3.0 assay (Bayer
      Diagnostics) for HCV RNA measurement in 344 samples derived from 120 patients
      with chronic genotype 1 HCV infection. The overall concordance between the
      results of the two tests was 95%, and the HCV RNA titers within the dynamic
      ranges of the assays correlated very well (r2=0.86). Furthermore, both tests
      performed equally well in determining an early viral response at week 1 or 4
      during antiviral therapy. We also compared two qualitative HCV RNA detection
      assays: the COBAS AMPLICOR HCV 2.0 assay versus the transcription-mediated
      amplification (TMA)-based VERSANT HCV RNA qualitative assay. Stored samples from
      sustained responders to interferon-ribavirin therapy were retested by the HCV TMA
      assay and were found to contain no detectable HCV RNA, demonstrating complete
      concordance between the results of PCR and TMA. However, HCV RNA was detected by
      the TMA assay in end-of-treatment (ETR) samples from 33% of patients with
      relapses who were HCV RNA negative according to the COBAS AMPLICOR assay. This
      observation suggests that a TMA assay can lead to a more correct definition of
      the ETR response.

PMID- 15956370
TI  - Evaluation of a novel rapid one-step immunochromatographic assay for detection of
      monoclonal Helicobacter pylori antigen in stool samples from children.
AB  - A new rapid one-step immunochromatographic test using monoclonal antibodies for
      detection of Helicobacter pylori antigen in stool in children was evaluated on
      coded stool samples from 159 children (mean age, 9.7 +/- 5.0 years; 118 from
      Munich, 41 from Vienna): 86 children were H. pylori infected defined by positive
      culture and/or > or =2 other positive tests ([13C]urea breath test, histology,
      rapid urease test), and 73 children showed concordant negative results. Seventy
      nine patients (12.1 +/- 3.8 years; 42 from Munich; 37 from Vienna) were tested 6
      to 8 weeks after anti-Helicobacter pylori therapy with urea breath test and stool
      test. In Munich, all 160 tests (118 pre- and 42 posttreatment) were independently
      read by two observers. Equivocal results were excluded for calculation of
      sensitivity and specificity but were considered as false to assess accuracy. The
      two observers in Munich agreed in 63 out of 65 positive and 89 out of 95 negative
      results, while eight times (5.0%) they judged the test as equivocal. Pretreatment
      and posttreatment results for sensitivity were 88.1% (79.2 to 94.1) and 88.9%
      (51.8 to 99.7), specificity 88.1% (77.8 to 94.1) and 93.9% (85.2 to 98.3), and
      accuracy 83.5% and 81.5%, respectively. We conclude that the new monoclonal
      immunochromatographic quick test shows a good interobserver agreement, but
      equivocal results occur in 5%. Performance is comparable before and after
      therapy. The test may become a good alternative in children in settings where a
      [13C]urea breath test or a reliable enzyme immunoassay stool test are not
      available.

PMID- 15956371
TI  - Characterization of Clostridium botulinum strains associated with an infant
      botulism case in the United Kingdom.
AB  - The sixth case of infant botulism in the United Kingdom was reported in 2001. The
      case was caused by a type B strain of Clostridium botulinum. Strains of C.
      botulinum were isolated from the baby's feces and from foodstuffs in the
      household in an attempt to document transmission. The aims of this study were to
      characterize the strains of C. botulinum associated with the botulism case. This
      was performed using a variety of techniques, including C. botulinum culture
      phenotypic properties, neurotoxin characterization, and pulsed-field gel
      electrophoresis (PFGE) banding patterns. Cultures associated with this case as
      well as isolates from stored and historical samples were analyzed and compared.
      C. botulinum type B PFGE patterns from the infant and from an opened container of
      infant formula were indistinguishable, while the PFGE profile of a strain
      presumably isolated from an unopened archival container was unique. The results
      suggest that the unopened brand of formula was not the source for transmission of
      spores to the infant and that the strain was distinct from previous botulism
      cases in the United Kingdom. Since environmental testing was not performed, it is
      not possible to deduce other sources of transmission.

PMID- 15956372
TI  - Outbreak of dysentery associated with ceftriaxone-resistant Shigella sonnei:
      First report of plasmid-mediated CMY-2-type AmpC beta-lactamase resistance in S.
      sonnei.
AB  - We document the first report of plasmid-encoded CMY-2-type AmpC beta-lactamase
      identified among Shigella sonnei isolates resistant to ceftriaxone and obtained
      after an outbreak of bacillary dysentery in Taiwan. One hundred eighty-two
      children in two elementary schools in Yu-Li, Taiwan, where an outbreak occurred
      after a typhoon hit this area in 2001, were enrolled in this study. Clinical and
      epidemiologic data on the infected children were collected. Pulsed-field gel
      electrophoresis (PFGE) was performed on the isolates to determine the genetic
      relatedness of outbreak strains. Plasmid analysis and PCR were performed to
      identify beta-lactamase genes responsible for ceftriaxone resistance. Forty-seven
      children from the two elementary schools were culture positive for S. sonnei in
      this outbreak. Twenty-three children were asymptomatic. Of the total isolates
      55.3% were resistant to ampicillin. One hundred percent of the isolates obtained
      from children in school A were initially susceptible to both ampicillin and
      ceftriaxone. Of isolates obtained from school B 96.2% were nonsusceptible to
      ceftriaxone. However, two isolates from school A developed resistance to
      ampicillin during the course of treatment. All 18 available isolates showed
      closely related PFGE patterns (4, 4a, 4b, and 4c). CMY-2-type AmpC beta-lactamase
      was responsible for ceftriaxone resistance in ceftriaxone-nonsusceptible
      isolates; Southern blot hybridization confirmed that such a resistance gene was
      located on the plasmid. This is the first report of plasmid-mediated CMY-2-type
      AmpC beta-lactamase in S. sonnei. Ampicillin-resistant isolates can develop
      during the course of antibiotic treatment.

PMID- 15956373
TI  - Selection of strains for quality assessment of the disk induction method for
      detection of inducible clindamycin resistance in Staphylococci: a CLSI
      collaborative study.
AB  - A nine-laboratory collaborative study was conducted to select positive and
      negative quality assessment control strains for the detection of inducible
      clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus
      were tested as unknowns on 10 different days in each laboratory using the
      recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum
      purity control method. Strains contained either macrolide-lincosamide
      streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a
      macrolide resistance efflux pump encoded by msr(A). Based upon the results of
      this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A)
      is recommended as the positive control organism for inducible clindamycin
      resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux
      pump encoded by msr(A), is recommended as the negative control organism.

PMID- 15956374
TI  - Development, technical performance, and clinical evaluation of a NucliSens basic
      kit application for detection of enterovirus RNA in cerebrospinal fluid.
AB  - The combination of nucleic acid sequence-based amplification and
      electrochemiluminescence detection was used to develop an internally controlled,
      highly sensitive and specific assay for the detection of enterovirus (EV) RNA in
      cerebrospinal fluid (CSF). The analytical performance of the assay was determined
      using both in vitro-transcribed EV RNAs and viral culture isolates. The
      sensitivity of the assay was 10 EV RNA copies per amplification reaction. The
      assay detected all enteroviral isolates tested with no cross-reactivity to 21
      nonenteroviral species, including rhinovirus and parechovirus. The clinical
      performance of the assay was evaluated by testing 992 CSF specimens collected
      from adult and pediatric patients. NucliSens EV results from a subset of 327 CSF
      samples were compared to viral culture of nasopharyngeal specimens and rectal
      swabs (n = 195) and/or CSF (n = 212). Of the 212 CSF samples, 96 samples were
      positive by either the NucliSens EV assay (94/96; 97.9%) or culture (63/96;
      65.6%), and 61/96 (63.5%) were positive by both methods. The inclusion of an EV
      specific internal control monitored the entire process, including the efficiency
      of nucleic acid extraction, amplification, and detection. In total, only five
      blood-clotted CSF samples (0.5%) were inhibited. The NucliSens EV assay
      demonstrated superior sensitivity over viral culture (P < 0.001), excellent
      specificity, clear delineation of positive samples, and minimal amplification
      inhibition.

PMID- 15956375
TI  - Distribution of nocardia species in clinical samples and their routine rapid
      identification in the laboratory.
AB  - Eighty-six Nocardia strains isolated from clinical samples in Belgium were
      identified by 16S rRNA gene sequencing. Eighty-three (96%) strains belonged to
      only six Nocardia species: N. farcinica (38 [44%]), N. nova (19 [22%]), N.
      cyriacigeorgica (13 [15%]), N. brasiliensis (6 [6.9%]), N. abscessus (5 [5.8%]),
      and N. paucivorans (2 [2.3%]). A gallery of nine conventional and enzymatic tests
      was developed for the rapid identification of the most common species isolated
      during this survey. Pyrrolidonyl aminopeptidase, gamma-glutamyl aminopeptidase,
      alpha-mannosidase, and alpha-glucosidase were found to be highly discriminating
      and could be used to develop an identification scheme.

PMID- 15956376
TI  - Nationwide antibiogram analysis using NCCLS M39-A guidelines.
AB  - Lack of standardization in antibiogram (ABGM) preparation (the overall profile of
      antimicrobial susceptibility results of a microbial species to a battery of
      antimicrobial agents) has not been addressed until recently. The objective of
      this study was to analyze current antibiograms using the recently published NCCLS
      M39-A guidelines for preparation of antibiograms to identify areas for
      improvement in the reporting of antibiogram susceptibility data. Antibiograms
      from across the United States were obtained by various methods, including direct
      mailings, Internet searches, and professional contacts. Each ABGM collected was
      analyzed using prospectively defined elements from the M39-A guidelines.
      Additionally, seven quality indicators were also evaluated to look for the
      reporting of any atypical or inappropriate susceptibility data. The 209
      antibiograms collected from 149 institutions showed at least 85% compliance to 5
      of the 10 M39-A elements analyzed. Clinically relevant elements not met included
      annual analysis, duplicate isolate notation, and the exclusion of organisms with
      fewer than 10 isolates. As for the quality indicators evaluated, unexpected
      results included the 7% of antibiograms that reported <100% vancomycin
      susceptibility for Staphylococcus aureus, 24% that had inconsistent beta-lactam
      susceptibility for Staphylococcus aureus, 20% that reported <100% imipenem
      susceptibility for Escherichia coli, and 37% that reported >0% ampicillin
      susceptibility for Klebsiella pneumoniae. These findings suggest that
      antibiograms should be reviewed thoroughly by infectious disease specialists
      (physicians and pharmacists), clinical microbiologists, and infection control
      personnel for identification of abnormal findings prior to distribution.

PMID- 15956377
TI  - High frequency of gastric colonization with multiple Helicobacter pylori strains
      in Venezuelan subjects.
AB  - Multiple Helicobacter pylori strains may colonize an individual host. Using
      enzyme-linked immunosorbent assay and line probe assay (LiPA) techniques, we
      analyzed the prevalence of mixed H. pylori colonization in 127 subjects from
      Venezuela, a country of high H. pylori prevalence, from three regions
      representing different population groups: the Andes (Merida), where Caucasian
      mestizos predominate, a major city near the coast (Caracas), where Amerindian
      Caucasian-African mestizos predominate, and an Amazonian community (Puerto
      Ayacucho), where Amerindians predominate and mestizos reflect Amerindian and
      Caucasian ancestry. Among 121 H. pylori-positive persons, the prevalence of cagA
      positive strains varied from 50% (Merida) to 86% (Puerto Ayacucho) by LiPA. Rates
      of mixed colonization also varied, as assessed by LiPA of the vacA s (mean, 49%)
      and m (mean, 26%) regions. In total, 55% of the individuals had genotypic
      evidence of mixed colonization. vacA s1c, a marker of Amerindian (East Asian)
      origin, was present in all three populations, especially from Puerto Ayacucho
      (86%). These results demonstrate the high prevalence of mixed colonization and
      indicate that the H. pylori East Asian vacA genotype has survived in all three
      populations tested.

PMID- 15956378
TI  - Pet dogs and chicken meat as reservoirs of Campylobacter spp. in Barbados.
AB  - Campylobacter spp. are the second most common pathogen isolated from stools of
      patients with gastroenteritis in Barbados. The aim of this study was to identify
      reservoirs of Campylobacter and the likely source(s) of human infection. Fecal
      specimens from 596 animals and 311 samples of animal food products were analyzed
      for the presence of Campylobacter spp. by standard culture techniques. Isolates
      were characterized by conventional phenotypic tests, confirmed by latex
      agglutination and PCR with genus-specific primers, and identified by the use of
      species-specific primers. High isolation rates were obtained for chickens
      (94.2%), pigs (90.5%), dogs (46.9%), cats (37.3%), and wild birds (39.3%).
      Campylobacter was also recovered from monkeys (17.1%) and sheep (4.2%) but not
      from cows. Chicken meat was frequently contaminated with Campylobacter (58.4%),
      but its recovery from other animal food products was rare. Campylobacter jejuni
      was the most commonly identified species in humans (63.6%), chickens (86.6%),
      dogs (51.5%), and chicken meat (79.8%). Porcine isolates were predominantly C.
      coli (98.4%), while cats harbored mainly C. upsaliensis and C. helveticus. Wild
      birds alone carried urease-positive thermophilic campylobacters. C. jejuni and C.
      coli isolates from different sources were compared with isolates from humans by
      randomly amplified polymorphic DNA typing with the primers OPA 11 and HLWL 85.
      Genotyping revealed similarities between isolates from chicken meat and those
      from humans and could not distinguish between two clinical isolates and four
      canine strains. Our results suggest that dogs are significant reservoirs of
      Campylobacter and contribute to human enteric infections and that chicken meat is
      a likely vehicle for the transmission of campylobacters to humans.

PMID- 15956379
TI  - Novel chemically modified liquid medium that will support the growth of seven
      bartonella species.
AB  - Bacteria of the genus Bartonella, a member of the Alphaproteobacteria, are
      fastidious, gram-negative, aerobic bacilli that comprise numerous species,
      subspecies, and subtypes. In human and veterinary medicine, species isolation
      remains a vital component of the diagnostic and therapeutic management of
      Bartonella infection. We describe a novel, chemically modified, insect-based
      liquid culture medium that supports the growth of at least seven Bartonella
      species. This medium will also support cocultures consisting of different
      Bartonella species, and it facilitated the primary isolation of Bartonella
      henselae from blood and aqueous fluid of naturally infected cats. This liquid
      growth medium may provide an advantage over conventional direct blood agar
      plating for the diagnostic confirmation of bartonellosis.

PMID- 15956380
TI  - Novel PCR-restriction fragment length polymorphism method for determining
      serotypes or serogroups of Streptococcus pneumoniae isolates.
AB  - Serotyping Streptococcus pneumoniae is a technique generally confined to
      reference laboratories, as purchasing pneumococcal antisera is a huge investment.
      Many attempts have been made to modify serological agglutination techniques to
      make them more accessible, and more recently developments in serotyping have
      focused on molecular techniques. This paper describes a PCR assay which amplifies
      the entire capsulation locus between dexB and aliA. Amplicons are digested to
      produce serotype-specific patterns. We have shown, using 81 epidemiologically
      unrelated strains representing 46 different serotypes, that the patterns
      correlate with a 90 to 100% similarity range for the same serotype or serogroup.
      Prospective testing of 73 isolates of unknown serotype confirmed reliable
      serotype attribution, and serotype profiles are reproducible on repeated testing.
      Once our database contains all 90 serotypes, this technique should be fully
      portable, cost-effective, and useful in any laboratory with sufficient molecular
      experience.

PMID- 15956381
TI  - comparison of two commercial assays for detection of human papillomavirus (HPV)
      in cervical scrape specimens: validation of the Roche AMPLICOR HPV test as a
      means to screen for HPV genotypes associated with a higher risk of cervical
      disorders.
AB  - Certain high-risk (HR) human papillomavirus (HPV) types are a necessary cause for
      the development of cervical disorders. Women with persistent HR HPV infections
      have an increased risk of developing high-grade cervical lesions, compared with
      those who have no or low-risk HPV infections. Therefore, implementation of HPV
      detection into cervical screening programs might identify women at risk of
      cervical cancer. Several HPV detection methods with different sensitivities and
      specificities are available. Recently, a new PCR-based technique, the Roche
      AMPLICOR HPV Test, was developed. This test recognizes a group of 13 HR HPV types
      simultaneously. This study was undertaken to validate and compare HPV detection
      in 573 cervical scrape specimens by the AMPLICOR HPV Test and the INNO-LiPA HPV
      detection/genotyping assay (SPF10-LiPA system version 1). Human beta-globin was
      not detected in nine specimens, which were therefore excluded from the
      comparison. Eleven scrape specimens containing HPV type 53 or 66 were also
      excluded from the comparison because these (probably) HR HPV types cannot be
      detected by the AMPLICOR HPV Test. The results of HPV detection by the Roche
      AMPLICOR HPV Test were confirmed by INNO-LiPA HPV detection/genotyping assay in
      539/553 cases, showing an absolute agreement of 97.5% with a Cohen's kappa of
      0.9327, indicating almost complete similarity of the two tests. Like the INNO
      LiPA HPV detection/genotyping assay, the AMPLICOR HPV Test was sensitive,
      specific, feasible, and easy to handle. The value of the Roche AMPLICOR HPV Test
      with a broad-spectrum HR HPV detection has to be determined in prospective
      clinical studies.

PMID- 15956382
TI  - Use of the duplex TaqMan PCR system for detection of Shiga-like toxin-producing
      Escherichia coli O157.
AB  - Real-time PCR assays have been applied for the detection and quantification of
      pathogens in recent years. In this study two combinations of primers and
      fluorescent probes were designed according to the sequences of the
      rfb(Escherichia coli O157) and stx2 genes. Analysis of 217 bacterial strains
      demonstrated that the duplex real-time PCR assay successfully distinguished the
      Escherichia coli O157 serotype from non-E. coli O157 serotypes and that it
      provided an accurate means of profiling the genes encoding O antigen and Shiga
      like toxin 2. On the other hand, bacterial strains that lacked these genes were
      not detected by this assay. The quantitative ranges of the real-time PCR assay
      for these two genes were linear for DNA concentrations ranging from 10(3) to
      10(9) CFU/ml of E. coli O157:H7 in pure culture and milk samples. The real-time
      PCR allowed the construction of standard curves that facilitated the
      quantification of E. coli O157:H7 in feces and apple juice samples. The detection
      sensitivity of the real-time PCR assay ranged from 10(4) to 10(9) CFU/g (or 10(4)
      to 10(9) CFU/ml) for feces and apple juice and 10(5) to 10(9) CFU/g for the beef
      sample without enrichment. After enrichment of the food samples in a modified
      tryptic soy broth, the detection range was from 10(0) to 10(3) CFU/ml. The real
      time PCR assays for rfb(E. coli) (O157) and stx2 proved to be rapid tests for the
      detection of E. coli O157 in food matrices and could also be used for the
      quantification of E. coli O157 in foods or fecal samples.

PMID- 15956383
TI  - Multilocus sequence typing for studying genetic relationships among Yersinia
      species.
AB  - The intra- and interspecies genetic relationships of 58 strains representing all
      currently known species of the genus Yersinia were examined by multilocus
      sequence typing (MLST), using sequence data from 16S RNA, glnA, gyrB, recA, and Y
      HSP60 loci. Yersinia aldovae, Y. bercovieri, Y. intermedia, Y. pestis, Y.
      pseudotuberculosis, Y. rohdei, and Y. ruckeri were genetically more homogeneous
      than were Y. enterocolitica, Y. frederiksenii, Y. kristensenii, and Y.
      mollaretii. The MLST data concerning the genetic relatedness within and among
      various species of Yersinia support the idea that Y. pestis and Y.
      pseudotuberculosis are two lineages within the same species rather than two
      distinct species. Y. ruckeri is the genetically most distant species within the
      genus. There was evidence of O-antigen switching and genetic recombination within
      and among various species of Yersinia. The genetic relatedness data obtained by
      MLST of the four housekeeping genes and 16S RNA agreed in most, but not all,
      instances. MLST was better suited for determining genetic relatedness among
      yersiniae than was 16S RNA analysis. Some strains of Y. frederiksenii and Y.
      kristensenii are genetically less related to other strains within those species,
      compared to strains of all other species within the genus. The taxonomic standing
      of these strains should be further examined because they may represent currently
      unrecognized Yersinia species.

PMID- 15956384
TI  - Molecular epidemiology of endemic Clostridium difficile infection and the
      significance of subtypes of the United Kingdom epidemic strain (PCR ribotype 1).
AB  - We previously identified two subtypes of the epidemic strain Clostridium
      difficile PCR ribotype 1, one clindamycin-sensitive strain (arbitrarily primed
      PCR [AP-PCR] type Ia) and a closely related clindamycin-resistant strain (AP-PCR
      type Ib) in our institution. We have now carried out prospective epidemiological
      surveillance for 4 years, immediately following the relocation of two acute
      medicine wards for elderly patients (wards A and B), to determine the clinical
      epidemiology of subtypes of the epidemic C. difficile PCR ribotype 1 group. To
      maximize the chance of strain discrimination, we used three DNA fingerprinting
      methods, AP-PCR, ribospacer PCR (RS-PCR), and pulsed-field gel electrophoresis
      (PFGE), to analyze C. difficile isolates recovered from symptomatic patients and
      from repeated environmental samplings. On ward B the incidence of C. difficile
      infection correlated significantly with the prevalence of environmental C.
      difficile both in ward areas closely associated with patients and health care
      personnel (r = 0.53; P < 0.05) and in high-reach sites (r = 0.85; P < 0.05). No
      such relationships were found on ward A. Seventeen distinct C. difficile
      genotypes were identified, 17 by AP-PCR, 12 by PFGE, and 11 by RS-PCR, but only 4
      of 17 genotypes caused patient infection. Isolates recovered from the hospital
      ward environment were much more diverse (14 genotypes). AP-PCR type Ia
      represented >90% of the C. difficile isolates. In addition to this genotype, only
      two others were isolated from both patient feces and environmental surfaces. AP
      PCR type Ib (clindamycin-resistant PCR ribotype 1 clone) was not associated with
      any cases of C. difficile infection and was isolated from the environment on only
      two occasions, after having been implicated in a cluster of six C. difficile
      infections 5 months before this study. The disappearance of this strain implies
      that differences in virulence and/or selective pressures may exist for this
      strain and the closely related, widespread C. difficile AP-PCR type Ia strain.
      Our findings emphasize the need to understand the epidemiology and virulence of
      clinically significant strains to determine successful control measures for C.
      difficile infections.

PMID- 15956385
TI  - Novel multipurpose methodology for detection of mycobacteria in pulmonary and
      extrapulmonary specimens by smear microscopy, culture, and PCR.
AB  - A novel, robust, reproducible, and multipurpose universal sample processing (USP)
      methodology for highly sensitive smear microscopy, culturing on solid and liquid
      media, and inhibition-free PCR which is suitable for the laboratory diagnosis of
      both pulmonary and extrapulmonary tuberculosis (TB) has been developed. This
      method exploits the chaotropic properties of guanidinium hydrochloride for sample
      processing and involves incubating the specimen with USP solution, concentrating
      bacilli by centrifugation, and using the processed specimen for smear microscopy,
      culture, and PCR. The detection limit for acid-fast bacilli in spiked sputum by
      smear microscopy is approximately 300 bacilli per ml of specimen. USP solution
      treated specimens are fully compatible with culturing on solid and liquid media.
      High-quality, PCR-amplifiable mycobacterial DNA can be isolated from all types of
      clinical specimens processed with USP solution. The method has been extensively
      validated with both pulmonary and extrapulmonary specimens. Furthermore, the USP
      method is also compatible with smear microscopy, culture, and PCR of mycobacteria
      other than tubercle bacilli. In summary, the USP method provides smear
      microscopy, culture, and nucleic acid amplification technologies with a single
      sample-processing platform and, to the best of our knowledge, is the only method
      of its kind described to date. It is expected to be useful for the laboratory
      diagnosis of TB and other mycobacterial diseases by conventional and modern
      methods.

PMID- 15956386
TI  - Utility of universal sample processing methodology, combining smear microscopy,
      culture, and PCR, for diagnosis of pulmonary tuberculosis.
AB  - The universal sample processing (USP) multipurpose methodology was developed for
      the diagnosis of tuberculosis (TB) and other mycobacterial diseases by using
      smear microscopy, culture, and PCR (S. Chakravorty and J. S. Tyagi, J. Clin.
      Microbiol. 43:2697-2702, 2005). Its performance was evaluated in a blinded study
      of 571 sputa and compared with that of the direct and N-acetyl L-cysteine (NALC)
      NaOH methods of smear microscopy and culture. With culture used as the gold
      standard, USP smear microscopy demonstrated a sensitivity and specificity of
      98.2% and 91.4%, respectively, compared to 68.6% and 92.6%, respectively, for the
      direct method. For a subset of 325 specimens, the USP method recorded a 97.1%
      sensitivity and 83.2% specificity compared to the NALC-NaOH method, which had a
      sensitivity and specificity of 80.0% and 89.7%, respectively, with culture used
      as the gold standard. Thus, the USP method exhibited a highly significant
      enhancement in sensitivity (P < 0.0001) compared to the direct and NALC-NaOH
      methods of smear microscopy. The USP culture sensitivity was 50.1% and was not
      significantly different from that of conventional methods (53.6%). The
      sensitivity and specificity of IS6110 PCR were 99.1% and 71.2%, respectively,
      with culture used as the gold standard, and increased to 99.7% and 78.8%,
      respectively, when compared with USP smear microscopy. Thus, the USP methodology
      was highly efficacious in diagnosing TB by smear microscopy, culture, and PCR in
      a clinical setting.

PMID- 15956387
TI  - Transfer and evaluation of an automated, low-cost real-time reverse transcription
      PCR test for diagnosis and monitoring of human immunodeficiency virus type 1
      infection in a West African resource-limited setting.
AB  - There is an urgent need for low-cost human immunodeficiency virus type 1 (HIV-1)
      viral load (VL) monitoring technologies in resource-limited settings. An
      automated TaqMan real-time reverse transcription-PCR (RT-PCR) assay was
      transferred to the laboratory of the Centre de Diagnostic et de Recherches sur le
      SIDA, Abidjan, Cote d'Ivoire, and assessed for HIV-1 RNA VL testing in 806 plasma
      samples collected within four ANRS research programs. The detection threshold and
      reproducibility of the assay were first determined. The quantitative results
      obtained with this assay were compared with two commercial HIV-1 RNA kits (the
      Versant version 3.0 and Monitor version 1.5 assays) in specimens harboring mainly
      the circulating recombinant form 02 strain (CRF02). The clinical evaluation of
      this test was done in different situations including the early diagnosis of
      pediatric infection and the monitoring of antiretroviral-treated patients. The
      quantification limit of our method was 300 copies/ml. The HIV-1 RNA values
      obtained by real-time PCR assay were highly correlated with those obtained by the
      Versant kit (r = 0.901; P < 0.001) and the Monitor test (r = 0.856; P < 0.001)
      and homogeneously distributed according to HIV-1 genotypes. For the early
      diagnosis of pediatric HIV-1 infection, the sensitivity and specificity of the
      real-time PCR assay were both 100% (95% confidence intervals of 93.7 to 100.0 and
      98.3 to 100.0, respectively), compared to the Versant results. Following
      initiation of antiretroviral treatment, the kinetics of HIV-1 RNA levels were
      very comparable, with a similar proportion of adults and children below the
      detection limit during follow-up with our technique and the Versant assay. The
      TaqMan real-time PCR (12 dollars per test) is now routinely used to monitor HIV-1
      infection in our laboratory. This technology should be further evaluated in
      limited-resource countries where strains other than CRF02 are prevalent.

PMID- 15956388
TI  - Prospective study of the prevalence, genotyping, and clinical relevance of
      Dientamoeba fragilis infections in an Australian population.
AB  - A prospective study was conducted over a 30-month period, in which fecal
      specimens from 6,750 patients were submitted to the Department of Microbiology at
      St. Vincent's Hospital, Sydney, Australia. Trophozoites of Dientamoeba fragilis
      were detected in 60 (0.9%) patients by permanent staining, and confirmation was
      performed by PCR. Gastrointestinal symptoms were present in all patients, with
      diarrhea and abdominal pain the most common symptoms. Thirty-two percent of
      patients presented with chronic symptoms. The average age of infected patients
      was 39.8 years. No correlation was found between D. fragilis and Enterobius
      vermicularis, a proposed vector of transmission for D. fragilis. The genetic
      diversity of 50 D. fragilis isolates was examined by PCR, and the PCR products
      were analyzed for the presence of restriction fragment length polymorphisms.
      These results showed no variation in the small-subunit rRNA gene and demonstrated
      a single genotype for all Australian isolates. This study shows the potential
      pathogenic properties of D. fragilis and the need for all laboratories to
      routinely test for this organism.

PMID- 15956389
TI  - Novel approach for assessing performance of PCR cyclers used for diagnostic
      testing.
AB  - As part of a large international project for validation and standardization of
      PCR, the influence of thermocyclers on PCR was tested. Six brand-new, Peltier
      technology-driven 96-well thermocyclers were subjected to a novel and stringent
      in-tube (not block) physical testing. The temperature was directly monitored in
      PCR tubes containing 50 microl of distilled water at 13 different block
      positions. The certified temperature accuracy of the measurement system was +/
      0.3 degrees C. Finally, the results of the physical testing were compared to
      those of an amplification efficiency study running an in-house PCR assay. The
      cyclers did not perform within the manufacturer's specification. Premature
      timing, under- and overshooting, and spatial variation of heat transfer were
      found to be the critical factors. The physical testing allowed us to distinguish
      accurate from less-accurate (2/6) cyclers. The lack of thermal homogeneities
      became most evident at the denaturation level during the first 15 s. At the time
      point zero, the accurate cyclers showed temperature deviations of 0.5 to 1.5
      degrees C, whereas less-accurate cyclers failed to reach the set temperature by
      13 to 20 degrees C. Consequently, the two less-accurate cyclers could not gain
      positive PCR results by running an in-house PCR assay. However, by modifying the
      original temperature protocol by increasing the denaturation temperature and
      time, the amplification efficiency of these two cyclers could be improved
      significantly. The results have implication for laboratories using diagnostic PCR
      testing.

PMID- 15956390
TI  - Emergence of fluconazole resistance in a Candida parapsilosis strain that caused
      infections in a neonatal intensive care unit.
AB  - Candida parapsilosis is an increasing cause of bloodstream infections (BSIs) in
      neonatal intensive care units (NICUs). It has been a persistent problem in the
      NICU of Hospital for Children and Adolescents, Helsinki University Central
      Hospital, Helsinki, Finland, since 1987. Fluconazole prophylaxis has been used to
      control the problem. The number of new infections has, however, increased
      markedly since September 2000. We assessed fluconazole consumption and occurrence
      of all Candida species in the NICU from 1991 to 2002. C. parapsilosis bloodstream
      isolates obtained in the NICU from 1990 to 2002 (n = 26) were genotyped and their
      fluconazole susceptibility was defined. A low rate of C. parapsilosis BSIs was
      correlated with high rates of consumption of fluconazole. No emergence of Candida
      species with primary resistance to fluconazole was detected. However, genotyping
      with a complex DNA fingerprinting probe revealed that a single strain of C.
      parapsilosis with decreasing susceptibility to fluconazole was responsible for
      cross-infections that caused BSIs in the NICU over a 12-year period. The
      emergence of fluconazole resistance in that strain was observed after more than
      10 years of fluconazole prophylaxis.

PMID- 15956391
TI  - Characterization of Salmonella enterica serovar Typhimurium and monophasic
      Salmonella serovar 1,4,[5],12:i:- isolates in Thailand.
AB  - Duplex PCR was developed to screen Salmonella enterica serovar Typhimurium phage
      type DT104 and related strains in Thailand because a phage typing laboratory of
      serovar Typhimurium is not available. Of 46 isolates of serovar Typhimurium and
      32 isolates of S. enterica serovar 1,4,[5],12:i:-, 15 (33%) and 30 (94%) were
      duplex PCR positive, respectively. All isolates were submitted for phage typing
      to analyze the specificity of the PCR assay. Among serovar Typhimurium isolates
      that yielded positive duplex PCRs, only seven isolates were phage types DT104 or
      U302, and eight isolates were undefined types, whereas the negative PCR isolates
      were either other phage types, including DT7, DT12, DT66, DT79, DT166, DT170,
      DT193, and DT208 or an undefined type. The serovar Typhimurium and serovar
      1,4,[5],12:i:- isolates that were duplex PCR positive were further subtyped by
      using XbaI PFGE to reveal their genetic relatedness. All serovar Typhimurium
      phage type DT104 strains had indistinguishable chromosomal patterns. The isolates
      of phage type U302 and most of the serovar 1,4,[5],12:i:- isolates that were
      duplex PCR positive yielded similar pulsed-field gel electrophoresis patterns.
      The patterns of PCR-negative isolates distinctly differed from the patterns of
      PCR-positive isolates. A total of 26% of all isolates had a dominant R-type
      ACSSuTG that was not found in the isolates of phage type DT104.

PMID- 15956392
TI  - Increase in genetic diversity of Haemophilus influenzae serotype b (Hib) strains
      after introduction of Hib vaccination in The Netherlands.
AB  - Recently, there has been an increase in The Netherlands in the number of cases of
      invasive disease caused by Haemophilus influenzae serotype b (Hib). To study a
      possible change in the Hib population that could explain the rise in incidence, a
      multiple-locus variable number tandem repeats analysis (MLVA) was developed to
      genotype H. influenzae isolates. The MLVA enabled the differentiation of H.
      influenzae serotype b strains with higher discriminatory power than multilocus
      sequence typing (MLST). MLVA profiles of noncapsulated H. influenzae and H.
      influenzae serotype f strains were more heterogeneous than serotype b strains and
      were distinct from Hib, although some overlap occurred. The MLVA was used to
      genotype a collection of 520 H. influenzae serotype b strains isolated from
      patients in The Netherlands with invasive disease. The strains were collected
      from 1983 from 2002, covering a time period of 10 years before and 9 years after
      the introduction of the Hib vaccine in the Dutch national vaccination program.
      MLVA revealed a sharp increase in genetic diversity of Hib strains isolated from
      neonates to 4-year-old patients after 1993, when the Hib vaccine was introduced.
      Hib strains isolated from patients older than 4 years in age were genetically
      diverse, and no significant change in diversity was seen after the introduction
      of the vaccine. These observations suggest that after the introduction of the Hib
      vaccine young children no longer constitute the reservoir for Hib and that they
      are infected by adults carrying genetically diverse Hib strains.

PMID- 15956393
TI  - Molecular epidemiology of a hepatitis C virus outbreak in a hemodialysis unit.
AB  - We analyzed a hepatitis C virus (HCV) transmission case in the hemodialysis unit
      of a private clinic by sequencing two genome regions of virus isolates from a
      number of patients attending this unit and some external controls. The analysis
      of 337 nucleotides (nt) in the NS5B region did not provide enough resolution to
      ascertain which patients were actually involved in the outbreak and the potential
      source. Nevertheless, this region allowed the exclusion of several patients as
      putative sources of the transmission case based on their genotypes and
      phylogenetic relationships. On the other hand, the analysis of several 472-nt
      long clone sequences per sample in a more rapidly evolving region of the HCV
      genome, coding for the envelope proteins and encompassing hypervariable region 1,
      allowed us to establish the existence of at least two independent transmission
      events involving two different source patients and three recipients. The
      direction of the transmissions was further corroborated by different measures of
      genetic variability within and among samples.

PMID- 15956394
TI  - Central European Dobrava Hantavirus isolate from a striped field mouse (Apodemus
      agrarius).
AB  - Dobrava virus (DOBV) is a hantavirus that causes hemorrhagic fever with renal
      syndrome (HFRS) in Europe. It is hosted by at least two rodent species, Apodemus
      flavicollis and A. agrarius. According to their natural hosts they form the
      distinct genetic lineages DOBV-Af and DOBV-Aa, respectively. We have now
      established a DOBV isolate named Slovakia (SK/Aa) from an A. agrarius animal
      captured in Slovakia. The complete S and M and partial L segment nucleotide
      sequences of the new isolate were determined. Phylogenetic analyses showed that
      the SK/Aa isolate clustered together with the other DOBV-Aa sequences amplified
      from A. agrarius before and can be taken as the representative of this genetic
      lineage. SK/Aa, in comparison with a DOBV-Af isolate, was used for serotyping
      neutralizing antibodies of HFRS patients in Central Europe. Most patients' sera
      exhibited a higher endpoint titer when probed with our new isolate, suggesting
      that DOBV-Aa strains are responsible for most of the DOBV-caused HFRS cases in
      this region.

PMID- 15956395
TI  - Comparative analysis of the diagnostic performance of six major Echinococcus
      granulosus antigens assessed in a double-blind, randomized multicenter study.
AB  - The serodiagnosis of hydatid disease is a valuable instrument for clinical
      diagnosis and epidemiological surveillance of high-risk populations. In the past
      decade a wealth of reports on the diagnostic performance of numerous antigens
      have been produced. However, their diagnostic value has been estimated under
      different conditions, using different serum collection, therefore precluding
      their direct comparison. Here we report an unbiased comparison of the same batch
      of six major E. granulosus antigens, namely, hydatid cyst fluid (HCF), native
      antigen B (AgB), two recombinant AgB subunits, an AgB-derived synthetic peptide,
      and recombinant cytosolic malate dehydrogenase from E. granulosus (EgMDH),
      against the same serum collection. The double-blind analysis was performed using
      a standardized protocol and receiver operating characteristic (ROC) data analysis
      by a network of six South American laboratories. High intercenter reproducibility
      was attained, and the intralaboratory analysis allowed the comparative ranking of
      the antigen panel. HCF, AgB, and its AgB8/1 subunit exhibited equivalent
      diagnostic efficiencies, 81.4% +/- 0.5%, 81.3% +/- 0.6%, and 81.9% +/- 2.0%,
      respectively; with a more favorable balance toward specificity in the case of the
      last antigen. The diagnostic efficiencies for the other three antigens were 76.8%
      +/- 6.8%, 69.1% +/- 2.7%, and 66.8% +/- 2.1%, for the peptide, the AgB8/2
      subunit, and the EgMDH, respectively. The study also included an analysis of
      batch-to-batch variation in the diagnostic performance of different HCF regional
      preparations. Based on these results, a suggested recommendation on the use of
      these antigens was drawn.

PMID- 15956396
TI  - Comparison of Campylobacter jejuni lipooligosaccharide biosynthesis loci from a
      variety of sources.
AB  - Campylobacter jejuni strains exhibit significant variation in the genetic content
      of the lipooligosaccharide (LOS) biosynthesis loci with concomitant differences
      in LOS structure. The C. jejuni LOS loci have been grouped into six classes based
      on gene content and organization. Utilizing PCR amplifications of genes from
      these loci, we were able to classify a majority (80%) of the LOS biosynthesis
      loci from 123 strains of C. jejuni that included 39 of the Penner serotype
      reference strains. We found that a particular LOS class was not always associated
      with a specific Penner serotype, and 14 of 16 Guillain-Barre syndrome-associated
      isolates tested in this study shared the same LOS class. The remaining isolates
      that could not be classified were often distinguishable from each other based on
      the results of gene-specific PCR and the lengths of their LOS biosynthesis loci
      as determined by long (XL) PCR. Sequence analysis of two of these unique XL PCR
      products demonstrated two new LOS classes. These results support the hypothesis
      that the LOS locus is a hot spot for genetic exchange and rearrangements.
      Analysis of the LOS biosynthesis genes by PCR assays can be used for typing C.
      jejuni and offers the advantage of inferring potential LOS structures.

PMID- 15956397
TI  - Isolation and molecular characterization of Staphylococcus sciuri in the hospital
      environment.
AB  - Staphylococcus sciuri is a principally animal-associated bacterial species, but
      its clinical relevance for humans is increasing. Our study aimed to provide the
      first insight into the prevalence of this bacterium in a hospital environment. A
      3-month surveillance was conducted in a hospital located in Belgrade, Serbia, and
      1,028 samples taken from hands of medical personnel, medical devices, and various
      hospital surfaces were screened for S. sciuri presence. In total, 108 isolates
      were obtained, which resulted in a relatively high rate of colonization (10.5%).
      These isolates, along with 7 S. sciuri strains previously isolated in the same
      hospital (n = 115), were phenotypically and genotypically characterized.
      Antimicrobial susceptibility testing revealed that 73% of the strains were
      resistant to one or more antibiotics, with 4.3% strains displaying
      multiresistance. Examination of 16S-23S ribosomal DNA intergenic spacer length
      polymorphism identified the strains at the subspecies level, and 74 (64.3%)
      strains of S. sciuri subsp. sciuri, 37 (32.2%) strains of S. sciuri subsp.
      rodentium, and 4 (3.5%) strains of S. sciuri subsp. carnaticus were established.
      Pulsed-field gel electrophoresis (PFGE) analysis showed 21 distinct pulsotypes,
      including 17 main types and 4 subtypes. One dominant cluster with 62 strains was
      found, while 19 (90.5%) of the PFGE types and subtypes identified had 5 or fewer
      strains. The predominance of small PFGE clusters suggests that the ubiquitous
      presence of S. sciuri in the outside environment presents the continuous source
      for colonization of the hospital environment. The presence of one dominant PFGE
      cluster of strains indicates that some S. sciuri strains may be capable for
      adaptation to hospital environment conditions and continuous existence in this
      environment.

PMID- 15956398
TI  - Development of a real-time, TaqMan reverse transcription-PCR assay for detection
      and differentiation of lyssavirus genotypes 1, 5, and 6.
AB  - Several reverse transcription-PCR (RT-PCR) methods have been reported for the
      detection of rabies and rabies-related viruses. These methods invariably involve
      multiple transfers of nucleic acids between different tubes, with the risk of
      contamination leading to the production of false-positive results. Here we
      describe a single, closed-tube, nonnested RT-PCR with TaqMan technology that
      distinguishes between classical rabies virus (genotype 1) and European bat
      lyssaviruses 1 and 2 (genotypes 5 and 6) in real time. The TaqMan assay is rapid,
      sensitive, and specific and allows for the genotyping of unknown isolates
      concomitant with the RT-PCR. The assay can be applied quantitatively and the use
      of an internal control enables the quality of the isolated template to be
      assessed. Despite sequence heterogeneity in the N gene between the different
      genotypes, a universal forward and reverse primer set has been designed, allowing
      for the simplification of previously described assays. We propose that within a
      geographically constrained area, this assay will be a useful tool for the
      detection and differentiation of members of the Lyssavirus genus.

PMID- 15956399
TI  - Discrimination between primary and secondary dengue virus infection by an
      immunoglobulin G avidity test using a single acute-phase serum sample.
AB  - For clinical and epidemiological purposes, it is necessary to be able to classify
      serological responses during dengue virus infection. Thus, it is important to
      develop a test that can distinguish between primary and secondary serological
      responses. The hemagglutination inhibition (HI) test, which is currently
      recommended by the World Health Organization, is complicated to perform. We
      developed an enzyme-linked immunosorbent assay based on changes in the avidity of
      immunoglobulin G during the infectious episode. This test can discriminate
      between primary and secondary infections by using a single serum sample collected
      during the acute phase of infection. We took 1,140 avidity measurements with 118
      pairs of serum samples or sequential samples taken from patients classified as
      having primary or secondary infection according to World Health Organization
      laboratory criteria. The mean percent avidity was significantly lower during
      primary infection (25.9%) than during secondary infection (66.3%) (Student t
      test, P < 0.001). The test had a sensitivity of 82.7% (95% confidence interval
      [CI] = 79.0 to 86.6) and a specificity of 77.5% (95% CI = 73.3 to 81.7). Based on
      analysis of only blood samples collected between the third and seventh days of
      the illness, during which most clinical complications occur, the sensitivity and
      specificity of the test were 95.1% (95% CI = 92.6 to 97.7) and 80.0% (95% CI =
      75.3 to 84.7), respectively. This rapid and simple test appears to be an
      excellent alternative to the HI test for discriminating between primary and
      secondary dengue virus infections during the acute phase of dengue.

PMID- 15956400
TI  - Epidemiologic relationship between fluoroquinolone-resistant Salmonella enterica
      Serovar Choleraesuis strains isolated from humans and pigs in Taiwan (1997 to
      2002).
AB  - The emergence of ciprofloxacin-resistant Salmonella enterica serovar Choleraesuis
      in recent years has become an important public health issue in Taiwan. The
      resistant strains that cause human infections are considered to be from pigs. In
      this study, we characterized 157 swine and 42 human Salmonella serovar
      Choleraesuis isolates by pulsed-field gel electrophoresis (PFGE) and drug
      susceptibility testing to investigate the epidemiologic relationship among the
      isolates. By PFGE analyses, two major clusters (clusters GA and GB) were
      identified. Isolates in cluster GA were of both human and swine origins, while
      those in cluster GB were from pigs only. Among the various genotypes identified,
      genotype gt-1a was the most prevalent, which was found in 71% (30 of 42) and 48%
      (76 of 157) of human and swine isolates, respectively. The susceptibility tests
      for the 106 gt-1a isolates identified 44 susceptibility profiles and showed that
      73% of human isolates and 34% of swine isolates were resistant to three
      fluoroquinolones (ciprofloxacin, enrofloxacin, and norfloxacin). Our findings
      indicate that a clonal group of Salmonella serovar Choleraesuis may have been
      circulating in human and swine populations in Taiwan for years and that the
      fluoroquinolone-resistant Salmonella serovar Choleraesuis strains most likely
      evolved from a gt-1a clone that emerged in 2000 and that then caused widespread
      infections in humans and pigs. Nevertheless, it is still debatable whether those
      Salmonella infections in humans are caused by isolates derived from pigs, on the
      basis of the higher fluoroquinolone and other antimicrobial resistance
      percentages in human isolates than in pig isolates.

PMID- 15956401
TI  - Unique endemicity of cryptosporidiosis in children in Kuwait.
AB  - To understand the transmission of Cryptosporidium infection in children, fecal
      specimens from 62 Kuwaiti children with gastrointestinal symptoms found to be
      positive by microscopy were genotyped and subtyped with a small subunit rRNA
      based PCR-restriction fragment length polymorphism analysis and a 60-kDa
      glycoprotein-based DNA sequencing tool. The median age of infected children was
      4.5 years, and 77% of infections occurred during the cool season of November to
      April. Fifty-eight of the children (94%) had Cryptosporidium parvum, three (5%)
      had Cryptosporidium hominis, and one (1%) had both C. parvum and C. hominis.
      Altogether, 13 subtypes of C. parvum (belonging to four subtype allele families)
      and C. hominis (belonging to three subtype allele families) were observed, with
      92% of specimens belonging to the common allele family IIa and the unusual allele
      family IId. Thus, the transmission of cryptosporidiosis in Kuwaiti children
      differed significantly from other tropical countries.

PMID- 15956402
TI  - Matrix-assisted laser desorption ionization-time of flight (mass spectrometry)
      for hepatitis C virus genotyping.
AB  - Determination of the hepatitis C virus (HCV) genotype has become accepted as the
      standard procedure in laboratory practice. Genotype assignment helps in disease
      prognosis and assists in establishing the appropriate duration of treatment. More
      than 10 types and 70 subtypes of HCV have been described. In Russia the most
      common subtypes are 1a, 1b, 2a, and 3a, and the types 4 and 5 are relatively
      rare. The "gold standard" for testing is gene sequencing. However, a variety of
      other assays had been developed to provide more rapid and cheaper forms of
      testing. The aim of this study was to determine the HCV genotype by
      minisequencing followed by matrix-assisted laser desorption ionization-time of
      flight (MALDI-TOF) mass spectrometry. Fragments of 5' untranslated region of the
      HCV genome were amplified. Three oligonucleotide primers were designed to detect
      two sets of genotype-specific single nucleotide polymorphisms. The primer
      extension reaction was performed using modified thermostable DNA polymerase and
      in the presence of dideoxynucleosides. The molecular weights of the reaction
      products were analyzed with MALDI-TOF mass spectrometer. The HCV genotype was
      determined by registering the particles of the expected molecular weights. The
      method was used to genotype HCV from HCV-positive blood sera or plasma. The 1a,
      1b, 2a, 3a, and 4 genotype HCVs were determined in the samples examined. The data
      were confirmed by direct sequencing. Thus, we propose a new accurate and
      efficient method for HCV genotyping based on minisequencing followed by mass
      spectrometry.

PMID- 15956403
TI  - Internal transcribed spacer rRNA gene-based phylogenetic reconstruction using
      algorithms with local and global sequence alignment for black yeasts and their
      relatives.
AB  - Sequences of rRNA gene internal transcribed spacer (ITS) of a standard set of
      black yeast-like fungal pathogens were compared using two methods: local and
      global alignments. The latter is based on DNA-walk divergence analysis. This
      method has become recently available as an algorithm (DNAWD program) which
      converts sequences into three-dimensional walks. The walks are compared with, or
      fit to, each other generating global alignments. The DNA-walk geometry defines a
      proper metric used to create a distance matrix appropriated for phylogenetic
      reconstruction. In this work, the analyses were carried out for species currently
      classified in Capronia, Cladophialophora, Exophiala, Fonsecaea, Phialophora, and
      Ramichloridium. Main groups were verified by small-subunit rRNA gene data. DNAWD
      applied to ITS2 alone enabled species recognition as well as phylogenetic
      reconstruction reflecting clades discriminated in small-subunit rRNA gene
      phylogeny, which was not possible with any other algorithm using local alignment
      for the same data set. It is concluded that DNAWD provides rapid insight into
      broader relationships between groups using genes that otherwise would be hardly
      usable for this purpose.

PMID- 15956404
TI  - Antifungal activities of tacrolimus and azole agents against the eleven currently
      accepted Malassezia species.
AB  - The lipophilic yeast Malassezia is an exacerbating factor in atopic dermatitis
      (AD) and colonizes the skin surface of patients with AD. With the goal of
      reducing the number of Malassezia cells, we investigated the antifungal
      activities of a therapeutic agent for AD, tacrolimus, and the azole agents
      itraconazole and ketoconazole against Malassezia species in vitro. We examined
      125 strains of the 11 currently accepted Malassezia species by using the agar
      dilution method. All strains of the 11 Malassezia species were very susceptible
      to both azole agents, with MICs ranging from 0.016 to 0.25 mug/ml. Tacrolimus had
      antifungal activities against half of the strains, with MICs ranging from 16 to
      32 mug/ml. Two of the major cutaneous floras, Malassezia globosa and Malassezia
      restricta, have several genotypes in the intergenic spacer region of the rRNA
      gene; the azole agents had slightly higher MICs for specific genotype strains of
      both microorganisms. A combination of azole agents and tacrolimus had a
      synergistic effect against Malassezia isolates, based on a fractional inhibitory
      index of 0.245 to 0.378. Our results provide the basis for testing these agents
      in future clinical trials to reduce the number of Malassezia cells colonizing the
      skin surface in patients with AD.

PMID- 15956405
TI  - Molecular epidemiology of community- and health care-associated methicillin
      resistant Staphylococcus aureus in Manitoba, Canada.
AB  - Recently, acquisition of methicillin-resistant Staphylococcus aureus (MRSA) has
      been increasingly seen in community settings. Beginning in 1995, we have
      routinely conducted pulsed-field gel electrophoresis (PFGE) of MRSA isolates
      received at Cadham Provincial Laboratory (CPL) in Manitoba, Canada. Our diverse
      collection of isolates coupled with molecular subtype information allowed us to
      assess the extent to which MRSA isolates in general were associated with
      community acquisition and whether specific PFGE types were more likely to be
      found in community settings. Forty percent of the MRSA isolates in our analysis
      were designated community associated (CA), with two of the six most common PFGE
      types showing a greater likelihood to be CA-MRSA. Overall, CA-MRSA were more
      likely to show multiple sensitivity to antibiotics and to be associated with
      younger age groups. Mapping of specific CA-MRSA types over successive 5-year
      periods showed rapid temporal shifts in prevalence in different parts of the
      province.

PMID- 15956406
TI  - Analysis of Bordetella pertussis populations in European countries with different
      vaccination policies.
AB  - Despite the widespread use of pertussis vaccines during the last decades,
      pertussis has remained an endemic disease with frequent epidemic outbreaks.
      Currently two types of vaccines are used: whole-cell vaccines (WCVs) and recently
      developed acellular vaccines (ACVs). The long-term aim of our studies is to
      assess the effect of different vaccination policies on the population structure
      of Bordetella pertussis and ultimately on the disease burden in Europe. In the
      present study, a total of 102 B. pertussis isolates from the period 1998 to 2001
      from five European countries (Finland, Sweden, Germany, The Netherlands, and
      France) were characterized. The isolates were analyzed by typing based on
      variable number of tandem repeats (VNTR); by sequencing of polymorphic genes
      encoding the surface proteins pertussis toxin S1 and S3 subunits (ptxA and ptxC),
      pertactin (prn), and tracheal colonization factor (tcfA); and by fimbrial
      serotyping. The results reveal a relationship between geographic location and
      VNTR types, the frequency of the ptxC alleles, and serotypes. We have not
      observed a relationship between the strain characteristics we studied and
      vaccination programs. Our results provide a baseline which can be used to reveal
      changes in the B. pertussis population in Europe in the coming years.

PMID- 15956408
TI  - Optimized diagnosis of acute dengue fever in Swedish travelers by a combination
      of reverse transcription-PCR and immunoglobulin M detection.
AB  - The dengue viruses (genus Flavivirus, family Flaviviridae) are mosquito borne and
      cause 100 million cases of dengue fever each year in most tropical and
      subtropical areas of the world. Increased global travel has been accompanied by
      an increased import not only of dengue but also of severe fevers of unknown
      origin to Sweden. Fifty-seven Swedish travelers to dengue epidemic areas, with
      clinical and serologically diagnosed dengue fever, were included in this study.
      To find fast and reliable methods to diagnose dengue in the early phase of the
      disease, patient acute-phase sera were investigated for the presence of dengue
      specific immunoglobulin M (IgM) antibodies by enzyme-linked immunosorbent assay
      (ELISA) and also for dengue serotype (DEN-1 to DEN-4)-specific RNA by different
      PCR assays. The results showed that 15/20 (75%) of the samples collected 5 days
      or later post onset of disease, but only 5/37 (14%) of the samples collected on
      days 0 to 4, contained dengue-specific IgM. Of the samples collected on days 0 to
      4 post onset, dengue RNAs of subtypes 1, 2, and 3 were detected by multiplex
      and/or by TaqMan PCR in 29/37 (78%); of these PCR-positive samples, 93% (27/29)
      were found IgM negative. By a combination of IgM ELISA and PCR assays, 84%
      (48/57) of the acute-phase samples were found to be positive. Our results
      demonstrated that detection of dengue viral RNA by reverse transcription-PCR and
      Taq-Man PCR is an excellent tool for the early diagnoses of dengue fever and that
      the IgM assay is a reliable complement for samples collected from day 5 post
      onset.

PMID- 15956407
TI  - Community-wide outbreaks of clonally related CTX-M-14 beta-lactamase-producing
      Escherichia coli strains in the Calgary health region.
AB  - Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) typically
      cause nosocomial infections. Previous surveillance in the Calgary Health Region
      showed that Escherichia coli strains producing ESBLs were common among community
      patients. During the period (2000 to 2002): 23 of 157 (15%) of the strains were
      positive for blaCTX-M genes from the CTX-M-I group (CTX-M-1-like) and 87 of 157
      (55%) of the strains were positive for blaCTX-M genes from the CTX-M-III group
      (CTX-M-14-like). The objective of this study was to investigate the molecular
      epidemiology of these strains. The beta-lactamases were characterized, and the
      genetic relatedness of the isolates was analyzed by digesting genomic DNA with
      the restriction endonuclease XbaI and by performing pulse-field gel
      electrophoresis (PFGE). PFGE revealed two closely related restriction patterns
      (clusters CTXM14A and CTXM14AR) among 67 (77%) CTX-M-14 producers. These strains
      from CTXM14A had nearly identical susceptibility patterns and were isolated most
      often from urine samples obtained at community sites during 2000 and 2001.
      Strains from the CTX-M-1-like and CTX-M-negative groups were unrelated to
      clusters CTXM14, CTXM14AR, and CTXM14NR. We conclude that clonally related
      strains of E. coli producing CTX-M-14 beta-lactamases were responsible for a
      predominantly community-wide outbreak. Further studies are warranted to
      investigate whether community-onset diseases caused by ESBL-producing E. coli are
      related to a point source or transmission within the community.

PMID- 15956409
TI  - Shifts of Bordetella pertussis variants in Sweden from 1970 to 2003, during three
      periods marked by different vaccination programs.
AB  - The Swedish population of Bordetella pertussis strains was characterized from
      1,247 isolates covering a whole-cell vaccine program up to 1979, a 17-year period
      without vaccination (1979 to 1996), and a period after the introduction of
      general vaccination among newborns with acellular pertussis vaccines (1997 to
      2003). Strains were characterized by serotyping and genotyping of pertactin and
      ptxA and by means of pulsed-field gel electrophoresis (PFGE). With emphasis on
      vaccine-related markers, the vast majority of circulating strains were of
      nonvaccine type. There were shifts of serotype connected with shifts of
      vaccination program. Serotype Fim3 was most frequent during the periods with
      general vaccination schedules, whereas serotype Fim2 was predominant during the
      17-year vaccine-free period. Pertactin 1 was predominant during the pertussis
      whole-cell (Pw) vaccine period but was thereafter replaced by prn2 and has not
      reappeared after the introduction of acellular pertussis (Pa) vaccines. ptxA (1)
      was predominant over all three decades. There was a significant difference in the
      distribution of serotypes between vaccinated and unvaccinated individuals, but
      not for pertactin. A few PFGE profiles were predominant over the years: BpSR25
      (serotype Fim3 prn1/7) and BpSR18 (serotype Fim3 prn2) during the Pw period,
      BpSR1 (serotype Fim2 prn2) during the 17 years without general vaccination, and
      BpSR11 (serotype Fim3 prn2) after the reintroduction of general vaccination in
      1996. Despite differences between the pertactin and toxin types of Pa vaccines
      and circulating strains, there is no evidence that there is a threat, i.e., the
      vaccination program so far has been effective against whooping cough, and there
      seems to be no impact on the effectiveness of the vaccination program from the
      bacterial polymorphism.

PMID- 15956410
TI  - Use of a BJAB-derived cell line for isolation of human herpesvirus 8.
AB  - Establishment of latently infected cell lines from primary effusion lymphomas
      (PEL) presently is the most efficient system for the propagation of clinical
      strains of human herpesvirus 8 (HHV-8) in culture. Here we describe a new
      approach to culture productively replicating HHV-8 from patient samples. A BJAB
      derived B-cell line, BBF, was found to retain HHV-8 longer, to support the latent
      and lytic replication programs, and to produce transmissible virus. Supernatants
      from n-butyrate-treated peripheral blood mononuclear cells of 24 HHV-8
      seropositive renal transplant recipients were used to infect BBF cells, and
      replicating virus was detected in cultures from 11 patients. Moreover, BBF cells
      infected with saliva strains showed a highly productive profile regardless of the
      initial viral load, which confirms that infectious HHV-8 can be present in saliva
      and also suggests that saliva strains may exhibit a high tropism for B
      lymphocytes. In conclusion, we established an in vitro system that efficiently
      detects HHV-8 in samples with low viral loads and that produces infectious
      progeny. BBF cells can be used to propagate HHV-8 from different biological
      samples as well as to clarify important issues related to virus-cell interactions
      in a context distinct from endothelial and PEL-derived cell lines.

PMID- 15956411
TI  - Species-level identification of staphylococcal isolates by real-time PCR and melt
      curve analysis.
AB  - A real-time PCR assay was developed to identify common staphylococcal species. A
      single set of consensus primers was designed to amplify a portion of the 16S rRNA
      gene, and a pair of fluorescence resonance energy transfer probes was used to
      identify species based on the unique melt properties of the probes resulting from
      sequence variations in the amplicons from each species. Nine common
      staphylococcal strains (S. aureus, S. capitis, S. epidermidis, S. haemolyticus,
      S. hominis, S. lugdunensis, S. schleiferi, S. simulans, and S. warneri) were used
      for assay development. The species-specific melting profiles were validated by
      correctly identifying 36 of 37 coagulase-negative staphylococcal (CoNS) isolates
      identified by ribotyping. In a study of clinical isolates, the PCR/melt curve
      approach correctly identified 56/56 S. aureus isolates identified by
      coagulase/protein A latex agglutination. Fifty-four CoNS clinical isolates
      characterized using the API Staph assay were studied, with the PCR/melt curve
      approach yielding matching identifications for 32/54 (59%). The API Staph assay
      was unable to identify 18 CoNS isolates, and differing results were obtained for
      4 isolates. Sequencing of the 22 discrepant or unidentified CoNS samples revealed
      that the PCR/melt curve results were correct for all but one isolate. Thus,
      PCR/melt curve analysis achieved a nearly 100% accuracy and performed better than
      biochemical testing. Performance of the PCR/melt curve approach requires less
      than 2 h after colony selection. This method thus provides a rapid and accurate
      approach to the identification of staphylococcal species in the clinical
      laboratory.

PMID- 15956412
TI  - Multiple copies of the 16S rRNA gene in Nocardia nova isolates and implications
      for sequence-based identification procedures.
AB  - Molecular investigation of two Nocardia patient isolates showed unusual
      restriction fragment length polymorphism patterns with restriction endonuclease
      assays (REA) using an amplified portion of the 16S rRNA gene. Patterns typical of
      Nocardia nova were obtained with REA of an amplified portion of the 65-kDa heat
      shock protein gene. Subsequent sequence analysis of the 16S rRNA gene regions of
      these isolates showed the presence of ambiguous bases within an expected
      restriction endonuclease recognition site which were not able to be resolved on
      repeat testing. Cloning of amplified regions of the 16S rRNA genes and subsequent
      sequencing of the resulting clones from the two patient isolates showed three
      different 16S rRNA gene sequences which corresponded to sequences found in N.
      nova, a molecular variant of N. nova, and a previously undescribed sequence.
      Hybridization studies using a DNA probe corresponding to an 89-bp conserved
      region of the 16S rRNA gene confirmed the presence of at least two copies of the
      16S rRNA gene in the N. nova type strain, in a patient isolate identical to the
      molecular variant of N. nova, and in the two other patient isolates. All isolates
      were found to belong to the species N. nova as determined by DNA-DNA
      hybridization. Because minimal variation has been found in the 16S rRNA gene
      sequences of different species of Nocardia, those laboratories employing
      molecular methods for identification of these species must be aware of the
      potential identification complications that may be caused by the presence of
      differing 16S rRNA genes in the same isolate.

PMID- 15956413
TI  - Genomic analysis of vaccine-derived poliovirus strains in stool specimens by
      combination of full-length PCR and oligonucleotide microarray hybridization.
AB  - Sabin strains of poliovirus used in the manufacture of oral poliovirus vaccine
      (OPV) are prone to genetic variations that occur during growth in cell cultures
      and the organisms of vaccine recipients. Such derivative viruses often have
      increased neurovirulence and transmissibility, and in some cases they can
      reestablish chains of transmission in human populations. Monitoring for vaccine
      derived polioviruses is an important part of the worldwide campaign to eradicate
      poliomyelitis. Analysis of vaccine-derived polioviruses requires, as a first
      step, their isolation in cell cultures, which takes significant time and may
      yield viral stocks that are not fully representative of the strains present in
      the original sample. Here we demonstrate that full-length viral cDNA can be PCR
      amplified directly from stool samples and immediately subjected to genomic
      analysis by oligonucleotide microarray hybridization and nucleotide sequencing.
      Most fecal samples from healthy children who received OPV were found to contain
      variants of Sabin vaccine viruses. Sequence changes in the 5' untranslated region
      were common, as were changes in the VP1-coding region, including changes in a
      major antigenic site. Analysis of stool samples taken from cases of acute flaccid
      paralysis revealed the presence of mixtures of recombinant polioviruses, in
      addition to the emergence of new sequence variants. Avoiding the need for cell
      culture isolation dramatically shortened the time needed for identification and
      analysis of vaccine-derived polioviruses and could be useful for preliminary
      screening of clinical samples. The amplified full-length viral cDNA can be
      archived and used to recover live virus for further virological studies.

PMID- 15956414
TI  - Rapid detection and differentiation of dengue virus serotypes by a real-time
      reverse transcription-loop-mediated isothermal amplification assay.
AB  - The development and validation of a one-step, real-time, and quantitative dengue
      virus serotype-specific reverse transcription-loop-mediated isothermal
      amplification (RT-LAMP) assay targeting the 3' noncoding region for the rapid
      detection and differentiation of dengue virus serotypes are reported. The RT-LAMP
      assay is very simple and rapid, wherein the amplification can be obtained in 30
      min under isothermal conditions at 63 degrees C by employing a set of four
      serotype-specific primer mixtures through real-time monitoring in an inexpensive
      turbidimeter. The evaluation of the RT-LAMP assay for use for clinical diagnosis
      with a limited number of patient serum samples, confirmed to be infected with
      each serotype, revealed a higher sensitivity by picking up 100% samples as
      positive, whereas 87% and 81% of the samples were positive by reverse
      transcription-PCR and virus isolation, respectively. The sensitivity and
      specificity of the RT-LAMP assay for the detection of viral RNA in patient serum
      samples with reference to virus isolation were 100% and 93%, respectively. The
      optimal assay conditions with zero background and no cross-reaction with other
      closely related members of the Flavivirus family (Japanese encephalitis, West
      Nile, and St. Louis encephalitis viruses) as well as within the four serotypes of
      dengue virus were established. None of the serum samples from healthy individuals
      screened in this study showed any cross-reaction with the four dengue virus
      serotype-specific RT-LAMP assay primers. These findings demonstrate that RT-LAMP
      assay has the potential clinical application for detection and differentiation of
      dengue virus serotypes, especially in developing countries.

PMID- 15956415
TI  - Comparison of immunohistochemistry and virus isolation for diagnosis of west nile
      virus.
AB  - Immunohistochemistry and virus isolation were performed on 1,057 birds.
      Immunohistochemistry, virus isolation, or both found 325 birds to be West Nile
      virus positive. Of these, 271 were positive by both methods. These results
      indicate that virus isolation and immunohistochemistry are approximately equal in
      their ability to detect West Nile virus.

PMID- 15956416
TI  - Multicenter evaluation of a Candida albicans peptide nucleic acid fluorescent in
      situ hybridization probe for characterization of yeast isolates from blood
      cultures.
AB  - We evaluated aliquots from 244 clinical blood culture bottles that demonstrated
      yeasts on Gram stain using a Candida albicans peptide nucleic acid (PNA)
      fluorescent in situ hybridization (FISH) probe. The sensitivity, specificity,
      positive predictive value, and negative predictive value of the C. albicans PNA
      FISH test in this study were 99%, 100%, 100%, and 99.3%, respectively.

PMID- 15956417
TI  - Clinical Relevance of the vacA, iceA, cagA, and flaA genes of Helicobacter pylori
      strains isolated in Eastern Taiwan.
AB  - The genotypes of Helicobacter pylori flaA, cagA, vacA, and iceA were determined
      for DNA isolated from patients with chronic gastritis or peptic ulcer in eastern
      Taiwan. The vacA gene encoding the s1a subtype was found to predominate in peptic
      ulcer patients, and the iceA1 genotype was associated with chronic gastritis.
      cagA and flaA genes were not found to be associated with these types of disease.

PMID- 15956418
TI  - Surveillance of Staphylococcus aureus in veterinary teaching hospitals.
AB  - Staphylococcus aureus isolates (n = 70) from 65 patients (36 canine, 18 equine, 7
      bovine, 2 avian, and 2 feline) at seven veterinary teaching hospitals in the
      United States were studied. The majority of patients (83%) with an S. aureus
      infection were canine and equine, but this may have reflected a sample bias based
      on clinic case loads and diagnostic lab submissions at the participating
      institutions. Fourteen percent of patients with an S. aureus infection were
      infected with a methicillin-resistant S. aureus (MRSA) isolate. Six of seven
      institutions had at least one MRSA infection during the study. Pulsed-field gel
      electrophoresis on 63 of the 70 isolates yielded 58 unique strains of S. aureus.
      None of the strain types of the MRSA isolates matched each other or the type of
      any other S. aureus isolate. The proportions of patients infected with an MRSA
      isolate were not significantly different between institutions or animal species
      (P > or = 0.222). Methicillin-resistant S. aureus isolates in this study seemed
      to be community acquired rather than hospital acquired.

PMID- 15956419
TI  - Evaluation of a new molecular system for simultaneous identification of four
      Enterococcus species and their glycopeptide resistance genotypes.
AB  - We compared the performances of a new DNA-based strip assay and the VITEK 2
      system for identification of 105 enterococcal strains and differentiation of
      their van gene-associated resistance levels. Both methods provided excellent
      results. The molecular assay showed advantages in time to result for
      identification of van-associated genes.

PMID- 15956420
TI  - Dissemination of multisusceptible methicillin-resistant Staphylococcus aureus in
      Singapore.
AB  - Analysis of hospital-acquired methicillin-resistant Staphylococcus aureus strains
      isolated from a tertiary public hospital in Singapore revealed that
      multisusceptible strains had gradually started to replace the endemic
      multiresistant strain (ST239-MRSA-III) since 2002. Molecular typing showed that
      this was a predominantly clonal outbreak of a UK-EMRSA-15 strain (ST22-MRSA-IV).

PMID- 15956421
TI  - Distribution of Burkholderia cepacia complex species among isolates recovered
      from persons with or without cystic fibrosis.
AB  - We analyzed Burkholderia cepacia complex isolates recovered from 1,218 cystic
      fibrosis (CF) patients and 90 patients without CF. Although all B. cepacia
      complex species were found, some were rarely identified. The distribution of
      species differed between the CF and non-CF populations and appears to be changing
      over time among CF patients.

PMID- 15956422
TI  - Cryptococcus neoformans Galactoxylomannan contains an epitope(s) that is cross
      reactive with Aspergillus Galactomannan.
AB  - We report a case of cryptococcosis in which a serum enzyme-linked immunosorbent
      assay (ELISA) for Aspergillus galactomannan was positive, with no evidence of
      aspergillosis. Soluble antigens from 19 Cryptococcus neoformans strains and
      purified carbohydrates of C. neoformans capsule were thus assayed in the
      Aspergillus galactomannan ELISA. Antigens from all C. neoformans strains, and
      purified galactoxylomannan, gave a positive reaction, suggesting that C.
      neoformans galactoxylomannan contains an epitope(s) that is cross-reactive with
      Aspergillus galactomannan.

PMID- 15956423
TI  - Shortcut method for extraction of Staphylococcus aureus DNA from blood cultures
      and conventional cultures for use in real-time PCR assays.
AB  - PCR allows rapid determination of both the presence of Staphylococcus aureus and
      of methicillin resistance. I present here a simple method for direct extraction
      from blood cultures or colonies for use in real-time PCR, eliminating tedious,
      time-consuming methods of DNA extraction which may otherwise deter microbiology
      labs from offering PCR.

PMID- 15956424
TI  - Molecular detection of a new Anaplasma species closely related to Anaplasma
      phagocytophilum in canine blood from South Africa.
AB  - Canine DNA samples from South Africa were found to contain 16S rRNA gene
      nucleotide and citrate synthase gene nucleotide and deduced amino acid sequences
      that were most similar to Anaplasma phagocytophilum: 98%, 66%, and 69%
      similarity, respectively. This suggests that a new Anaplasma species closely
      related to A. phagocytophilum occurs in Africa.

PMID- 15956425
TI  - Four laboratory-associated cases of infection with Escherichia coli O157:H7.
AB  - An investigation of four cases of infection with Escherichia coli O157:H7 among
      laboratorians from different clinical laboratories revealed that the DNA
      fingerprint pattern of each case isolate was indistinguishable from that of an
      isolate handled in the laboratory prior to illness. These data suggest that the
      infections were laboratory acquired, and they demonstrate the importance of
      laboratorians strictly adhering to biosafety practices recommended for the
      handling of infectious materials.

PMID- 15956426
TI  - Enteropathogenic Escherichia coli strains carrying genes encoding the PER-2 and
      TEM-116 extended-spectrum beta-lactamases isolated from children with diarrhea in
      Uruguay.
AB  - We studied 13 extended-spectrum beta-lactamase (ESBL)-producing enteropathogenic
      Escherichia coli isolates from children suffering acute diarrhea in Uruguay. ESBL
      characterization in crude extracts showed a single band at pI 5.4. PCR
      amplification and sequencing data allowed identification of blaPER-2 and blaTEM
      116. Retrospective analysis suggests that these strains were disseminated in the
      community, even if unnoticed, prior to their access to the hospital environment
      more than a decade ago.

PMID- 15956427
TI  - Multiplex PCR for direct detection of Shiga toxigenic Escherichia coli strains
      producing the novel subtilase cytotoxin.
AB  - We have recently described a novel AB5 subtilase cytotoxin produced by certain
      Shiga toxigenic Escherichia coli (STEC) strains. This potentially lethal toxin
      may contribute to severe gastrointestinal and systemic disease in humans. In this
      study we have developed a trivalent PCR assay for the detection of the novel
      toxin A subunit gene subA, as well as stx1 and stx2. The three primer pairs used
      in the assay do not interfere with each other and generate amplification products
      of 556, 180, and 255 bp, respectively. The assay can be used for determining the
      toxin genotype of STEC isolates, as well as for direct detection of toxin genes
      in primary fecal culture extracts.

PMID- 15956428
TI  - Use of the genomic subtractive hybridization technique to develop a real-time PCR
      assay for quantitative detection of Prevotella spp. in oral biofilm samples.
AB  - Genomic subtractive hybridization was used to design Prevotella nigrescens
      specific primers and TaqMan probes. Based on this technique, a TaqMan real-time
      PCR assay was developed for quantifying four oral black-pigmented Prevotella
      species. The combination of real-time PCR and genomic subtractive hybridization
      is useful for preparing species-specific primer-probe sets for closely related
      species.

PMID- 15956429
TI  - Use of genotypic identification by sodA sequencing in a prospective study to
      examine the distribution of coagulase-negative Staphylococcus species among
      strains recovered during septic orthopedic surgery and evaluate their
      significance.
AB  - A total of 212 coagulase-negative Staphylococcus strains recovered prospectively
      during 119 surgeries for proven or suspected bone and joint infection (BJI) were
      identified by sodA sequencing. These strains were identified as 151
      Staphylococcus epidermidis isolates, 15 S. warneri isolates, 14 S. capitis
      isolates, 9 S. hominis isolates, 6 S. lugdunensis isolates, 5 S. haemolyticus
      isolates, 4 S. caprae isolates, 4 S. pasteuri isolates, 3 S. simulans isolates,
      and 1 S. cohnii isolate. Only S. epidermidis, S. lugdunensis, S. capitis, and S.
      caprae were found to be infecting organisms and were involved, respectively, in
      35 (81.4%), 3 (7.0%), 3 (7.0%), and 2 (4.6%) cases of BJI.

PMID- 15956430
TI  - Gene mutations responsible for overexpression of AmpC beta-lactamase in some
      clinical isolates of Enterobacter cloacae.
AB  - AmpC regulatory genes in 21 ceftazidime-resistant clinical isolates of
      Enterobacter cloacae (MICs of > or = 16 microg/ml) were characterized. All
      isolates exhibited AmpC overproduction due to AmpD mutation. Additionally, we
      found two AmpR mutants among the isolates. This is the first report of
      chromosomal ampR mutation in clinical isolates of E. cloacae.

PMID- 15956431
TI  - Molecular epidemiology investigation of outbreaks of fowl cholera in
      geographically related poultry flocks.
AB  - The present work describes two cases of consecutive fowl cholera outbreak series
      occurring in goose and turkey flocks. Most strains isolated from
      epidemiologically related outbreaks showed genetic relatedness, as revealed by
      enterobacterial repetitive intergenic consensus-PCR and pulsed-field gel
      electrophoresis, suggesting that the consecutive outbreaks were due to
      recurrences rather than reinfections.

PMID- 15956432
TI  - Quinolone-resistant uropathogenic Escherichia coli strains from phylogenetic
      group B2 have fewer virulence factors than their susceptible counterparts.
AB  - The prevalence of 31 virulence factors was analyzed among nalidixic acid
      susceptible and -resistant Escherichia coli strains from phylogenetic group B2.
      Hemolysin, cytotoxic necrotizing factor 1, and S and F1C fimbriae genes were less
      prevalent among nalidixic acid-resistant E. coli strains. Quinolone resistance
      may be associated with a decrease in the presence of some virulence factors.

PMID- 15956433
TI  - Occurrence of hlyA and sheA genes in extraintestinal Escherichia coli strains.
AB  - The association of a hemolytic phenotype with the carriage of the alpha-hemolysin
      gene (hlyA) and/or the silent hemolysin gene (sheA or clyA) among 540
      extraintestinal clinical isolates of Escherichia coli and 110 fecal isolates from
      healthy individuals was investigated. Though HlyA is an important virulence
      factor in extraintestinal E. coli infection, the role of SheA is not completely
      clarified. Two hemolytic sheA+ E. coli strains that lacked hlyA and possessed no
      other hemolysin genes were identified. No hlyA+ sheA+ strains were identified,
      suggesting that there is possible incompatibility between hlyA and sheA in the
      chromosome of E. coli.

PMID- 15956434
TI  - Survey of methicillin-resistant Staphylococcus aureus strains from two hospitals
      in El Paso, Texas.
AB  - Seventy-one percent of 76 methicillin-resistant Staphylococcus aureus (MRSA)
      strains isolated from two medical centers in El Paso, Texas, represent three
      similar pulsed-field gel electrophoresis types. Overall, six pulsed-field types
      were identified represented by multilocus sequence/staphylococcal chromosomal
      cassette DNA mec (SCCmec) types: ST5-MRSA-II; ST36-MRSA-II; ST8 (untypeable
      SCCmec); and a newly described clonal cluster 8 strain, ST507-MRSA-IV. This study
      demonstrates the presence of multiple-antibiotic-resistant epidemic MRSA clones
      in El Paso.

PMID- 15956435
TI  - Molecular diagnosis of lymphogranuloma venereum in patients with genital ulcer
      disease.
AB  - The detection of herpes, chancroid, and syphilis in genital ulcers is done by
      PCR. This is not so for lymphogranuloma venereum (LGV). We report on the use of a
      PCR with digestion that differentiates the LGV biovar from the trachoma biovar.
      Our findings suggest that the clinical description of LGV in current textbooks is
      incomplete.

PMID- 15956436
TI  - Isolation and characterization of Mycoplasma sphenisci sp. nov. from the choana
      of an aquarium-reared jackass penguin (Spheniscus demersus).
AB  - Strain UCMJ was isolated from the choana of a jackass penguin (Spheniscus
      demersus) with recurrent mucocaseous choanal discharge. Isolation of this
      mycoplasma expands the known range of species hosting mycoplasmas. The name
      Mycoplasma sphenisci sp. nov. is proposed for this new species, for which strain
      UCMJ is the type strain.

PMID- 15956437
TI  - Demonstration of a high level of parasite population homology by quantification
      of Plasmodium falciparum alleles in matched peripheral, placental, and umbilical
      cord blood samples.
AB  - Plasmodium falciparum msp-1 and msp-2 genes were quantified by fragment analysis
      in matched placental, peripheral, and cord blood samples. In the three
      compartments, the multiplicity of infection values were similar, and parasite
      populations only partially overlapped, as reported. However, identical alleles
      represented 80 to 95% of the overall parasite populations of each compartment,
      demonstrating much more homogenous parasite populations than previously thought.

PMID- 15956438
TI  - Prevalence of Helicobacter pullorum among patients with gastrointestinal disease
      and clinically healthy persons.
AB  - Feces from 531 patients with gastroenteritis and from 100 clinically healthy
      individuals were tested for Helicobacter pullorum by use of PCR. Samples positive
      by PCR were qualified for isolation. H. pullorum DNA was demonstrated to be
      present in feces from 4.3% of patients with gastrointestinal disease but also in
      feces from 4.0% of clinically healthy persons. One strain was isolated from one
      patient with gastrointestinal disease.

PMID- 15956439
TI  - Species-level molecular identification of invasive "Streptococcus milleri" group
      clinical isolates by nucleic acid sequencing in a centralized regional
      microbiology laboratory.
AB  - Organisms belonging to the "Streptococcus milleri" group are important invasive
      human pathogens. A detailed understanding of their pathogenesis in human
      infection has only recently been facilitated by the use of molecular methods to
      study this group of organisms.

PMID- 15956440
TI  - Cryptococcal antigen test revisited: significance for cryptococcal meningitis
      therapy monitoring in a tertiary chinese hospital.
AB  - For a total of 29 non-human immunodeficiency virus 1 cryptococcal meningitis
      cases, titer changes in the latex agglutination test before and after therapy
      were reviewed along with clinical manifestations, laboratory findings, and
      therapy regimens. The cryptococcal antigen titer decreased for every case after
      therapy and was correlated to fungal clearance as defined by fungus smear and/or
      culture. However, cryptococcal antigen can remain at low titers for long periods
      of time after therapy, even when fungus smears and/or cultures become negative.

PMID- 15956441
TI  - Multicenter evaluation of a semiautomated, standardized assay for detection of
      hepatitis B virus DNA in blood donations.
AB  - We evaluated the COBAS Ampliscreen hepatitis B virus (HBV) test using standards,
      seroconversion panels, consecutive donations, and samples from patients with
      abnormal alanine aminotransferase and chronic hepatitis C. Specificity was 100%
      and sensitivity was 20 IU/ml. In seroconversion panels, HBV DNA was detected up
      to 4 to 18 days before HBsAg, suggesting that this assay is useful in shortening
      the infectious window phase.

PMID- 15956442
TI  - Frequency of sample submission for optimal utilization of the cell culture
      cytotoxicity assay for detection of Clostridium difficile toxin.
AB  - We reviewed the results of repeated sample submissions within a 7-day time frame
      for Clostridium difficile toxin testing. A total of 2,940 samples were tested
      during a 3-month period using a cell culture cytotoxicity assay (CCCA). The
      results from all second samples (n = 1,101) were concordant with the original
      test result. In only two cases (0.8%; n = 247) was a third sample positive when
      the first two samples were negative. In this study, submission of multiple
      samples for CCCA did not increase detection of Clostridium difficile infection.

PMID- 15956443
TI  - Extraction of Mycobacterium tuberculosis DNA: a question of containment.
AB  - DNA fingerprinting of Mycobacterium tuberculosis by IS6110 restriction fragment
      length polymorphism analysis requires substantial high-quality DNA. We
      demonstrated that, despite extraction treatments that might be expected to
      inactivate this organism, M. tuberculosis remained viable during this process.
      These data suggest that the extraction of M. tuberculosis DNA should be performed
      within containment until complete.

PMID- 15956444
TI  - Shared genotypes of Achromobacter xylosoxidans strains isolated from patients at
      a cystic fibrosis rehabilitation center.
AB  - During a study examining transmission of Pseudomonas aeruginosa among 76 cystic
      fibrosis patients in a rehabilitation center, where patients stay in close
      contact during prolonged periods, several clusters of patients carrying
      genotypically identical P. aeruginosa, as well as two clusters of 4 and 10
      patients, respectively, colonized with genotypically identical Achromobacter
      xylosoxidans strains, were discovered.

PMID- 15956445
TI  - Inability to make a premortem diagnosis of Acanthamoeba species infection in a
      patient with fatal granulomatous amebic encephalitis.
AB  - Granulomatous amebic encephalitis (GAE), an infection of immunocompromised hosts,
      is almost uniformly fatal. A case of GAE in a patient who failed to mount a
      serologic response to Acanthamoeba polyphaga is presented. Although Acanthamoeba
      polyphaga that is sensitive to multiple antimicrobials grew from brain tissue, an
      inability to make a premortem diagnosis precluded therapy.

PMID- 15956446
TI  - First identification of Clostridium celerecrescens in liquid drained from an
      abscess.
AB  - We present the first report on the characterization of Clostridium celerecrescens
      isolated from liquid drained via abscess puncture from a 45-year-old man. The
      organism was identified by sequence comparison of 16S rRNA genes.

PMID- 15956447
TI  - Recurrent breast abscess caused by Gordonia bronchialis in an immunocompetent
      patient.
AB  - We present the first reported case of a recurrent breast infection caused by
      Gordonia bronchialis. The infection occurred in a 43-year-old immunocompetent
      female, and species level identification was obtained with 16S rRNA sequencing.

PMID- 15956448
TI  - Infection by Chlamydophilia avium in an elderly couple working in a pet shop.
AB  - Psittacosis infection is usually reported in adults aged around 30 to 60 years.
      We report here two cases of psittacosis in an elderly couple (76 and 77 years
      old) who jointly ran a pet shop. Psittacosis was diagnosed from a history of
      exposure to birds and from serological testing for Chlamydophilia avium.

PMID- 15956449
TI  - Atypical serological response marked by a lack of detectable anti-gp43 antibodies
      in a patient with disseminated paracoccidioidomycosis.
AB  - Serological tests are frequently used to diagnosis paracoccidioidomycosis. A
      glycoprotein of 43 kDa is considered to be the main diagnostic antigen, being
      recognized by virtually all patients' sera. A case of atypical serological
      response, consisting of a lack of detectable anti-gp43 antibodies, in a patient
      with disseminated paracoccidioidomycosis is presented.

PMID- 15956450
TI  - Disseminated coinfection with Actinomyces graevenitzii and Mycobacterium
      tuberculosis: case report and review of the literature.
AB  - We report the first case of disseminated infection with both Actinomyces
      graevenitzii and Mycobacterium tuberculosis and review the medical literature.
      Concomitant actinomycosis and tuberculosis is very rare. The potential of the
      facultatively aerobic, newly described A. graevenitzii for disseminated invasive
      infection needs to be evaluated.

PMID- 15956451
TI  - First reported case of endocarditis caused by Candida dubliniensis.
AB  - Candida dubliniensis is an uncommon cause of bloodstream infection. We describe
      the first reported case of endocarditis caused by C. dubliniensis and the use of
      a rapid and novel real-time PCR assay based on the internal transcribed spacer 2
      variable region of the rRNA operon that was used to identify this organism.

PMID- 15956452
TI  - New A/H3N2 influenza variant: a small genetic evolution but a heavy burden on the
      Italian population during the 2004-2005 season.

PMID- 15956453
TI  - Chlamydia pneumoniae in peripheral blood mononuclear cells isolated from
      individuals younger than 20 years or older than 60 years.

PMID- 15956454
TI  - Low positive predictive values and specificities of spoligotyping and
      mycobacterial interspersed repetitive unit-variable-number tandem repeat typing
      methods for performing population-based molecular epidemiology studies of
      tuberculosis.

PMID- 15956455
TI  - Evaluation of approaches to detect quantitative trait loci for growth, carcass,
      and meat quality on swine chromosomes 2, 6, 13, and 18. I. Univariate outbred F2
      and sib-pair analyses.
AB  - Results from univariate outbred F2 interval mapping and sib-pair analyses of 12
      growth and 28 carcass traits to identify QTL on SSC 2, 6, 13, and 18 were
      compared. Phenotypic and genetic data were recorded on a three-generation
      resource population including 832 F2 pigs from a cross between three Berkshire
      sires and 18 Duroc dams. Thirty markers with an average spacing of approximately
      16 cM were genotyped across the four chromosomes. The outbred F2 mixed model
      included the effects of sex, birth month, and year, one-QTL additive, dominance
      and imprinting coefficients calculated every 1 cM using interval mapping, and a
      random family effect. The general sib-pair model used to describe the phenotypic
      differences between sib-pairs included the same systematic and random effects and
      a one-QTL additive coefficient calculated every 1 cM. The outbred F2 analysis
      found significant evidence of QTL on SSC 2 associated with 105-d weight, backfat
      thicknesses, LM area, fat percent, shear force, juiciness, marbling, and
      tenderness. In addition, QTL were identified on SSC 6 relating to 42-d weight and
      LM area, and on SSC 18 for fat and moisture percents. In most instances, the
      outbred F2 approach offered greater power to detect QTL; however, the sib-pair
      analysis offered greater power in several instances. The trait-specific
      superiority could be due to the relative advantage of each model within a trait
      data set. The two approaches provided complementary evidence for QTL segregating
      between the Berkshire and Duroc breeds used in the study that may be used to aid
      marker-assisted introgression and selection and candidate gene studies to improve
      swine growth and meat quality characteristics.

PMID- 15956456
TI  - Biological responses to porcine respiratory and reproductive syndrome virus in
      pigs of two genetic populations.
AB  - One hundred pigs from the NE Index Line (NEI) and 100 Hampshire-Duroc cross pigs
      (HD) were inoculated intranasally with porcine respiratory and reproductive
      syndrome virus (PRRSV 97-7895 strain) at 26 d of age to determine whether genetic
      variation in response to PRRSV exists. An uninfected littermate to each infected
      pig served as a control. Pigs were from 163 dams and 83 sires. Body weight and
      rectal temperature were recorded, and blood samples were drawn from each pig on d
      0 before inoculation and on d 4, 7, and 14 after inoculation. Pigs were
      sacrificed on d 14. Lung and bronchial lymph nodes were collected, placed in
      optimal cutting temperature compound, and frozen at -80 degrees C. The presence
      of PRRSV in serum and in lung tissue and bronchial lymph nodes was determined by
      isolation in cell culture. The presence of antibodies in serum collected on d 14
      was determined by a commercial ELISA test. Lung tissue was examined
      microscopically and scored for incidence and severity of lesions (score of 1 to
      3; 1 = no or few lesions, and 3 = severe interstitial pneumonia). Data were
      analyzed with a mixed model that included random sire and dam effects. The
      interaction of line x treatment was significant (P < 0.001) for weight change and
      rectal temperature. Un-infected HD pigs gained 0.67 kg more from d 0 to 14 and
      averaged 0.32 degrees C higher rectal temperature than uninfected NEI pigs (P <
      0.001), whereas infected NEI pigs gained 0.34 kg more and had -0.54 degrees C
      lower temperature than infected HD pigs (P < 0.001). Viremic titer (cell culture
      infectious dose 50%/mL) was greater (P < 0.05) in HD than NEI at d 4 (10(4.52)
      vs. 10(4.22)), 7 (10(4.47) vs. 10(3.99)), and 14 (10(3.49) vs. 10(3.23)). Viral
      titer loads in lung (P = 0.11) and bronchial lymph nodes tended (P = 0.07) to be
      greater in HD than NEI pigs. Antibody signal-to-positive (S/P) ELISA ratios in
      infected pigs ranged from 0.18 to 3.38, and 88% had levels > or = 0.40, which is
      the positive threshold for this ELISA. The S/P range in uninfected pigs was 0 to
      1.11, and 99% had levels < or = 0.40. Mean S/P ratio for infected pigs was 0.23
      units higher in HD than in NEI (P < 0.001). The HD pigs had a greater incidence
      of interstitial pneumonia and 0.65 higher mean lesion scores than NEI pigs (P <
      0.001). In summary, responses of pigs of the two lines to infection with PRRSV
      differed, indicating that underlying genetic variation existed.

PMID- 15956457
TI  - Genotype x environment interaction effects on carcass traits in Japanese Black
      cattle.
AB  - The importance of genotype x environment (region or management system)
      interactions for carcass traits in Japanese Black cattle was investigated using
      both univariate and multivariate animal models. The univariate approach was used
      mainly to test the significance of interaction effects. The multivariate approach
      was used to estimate genetic correlations, which indicated the magnitude of
      genotype x environment (GE) interactions. The more a genetic correlation deviates
      from 1, the larger the interaction. From the univariate approach, the addition of
      genotype x environment (region or management system) interaction (co)variance
      components resulted in an improved fit of the model for all traits in both cases
      (P < 0.001). However, estimates of genetic correlation between regions obtained
      from the multivariate approach for hot carcass weight, LM area, rib thickness,
      s.c. fat thickness, and marbling score were 0.97, 0.95, 0.93, 0.97, and 0.93,
      respectively. The corresponding estimates between management systems were 0.84,
      0.92, 0.84, 0.90, and 0.97, respectively. These results indicate that GE
      interaction effects on carcass traits of Japanese Black cattle may be
      biologically unimportant. Therefore, breeding values obtained using the
      multivariate method would rank sires similarly in all environments. Consequently,
      carcass traits measured in these two different regions or management systems can
      be treated as the same traits.

PMID- 15956458
TI  - Estimates of genetic correlations between days to calving and reproductive and
      weight traits in Nelore cattle.
AB  - Data comprising 53,181 calving records were analyzed to estimate the genetic
      correlation between days to calving (DC), and days to first calving (DFC), and
      the following traits: scrotal circumference (SC), age at first calving (AFC), and
      weight adjusted for 550 d of age (W550) in a Nelore herd. (Co)variance components
      were estimated using the REML method fitting bivariate animal models. The fixed
      effects considered for DC were contemporary group, month of last calving, and age
      at breeding season (linear and quadratic effects). Contemporary groups were
      composed by herd, year, season, and management group at birth; herd and
      management group at weaning; herd, season, and management group at mating; and
      sex of calf and mating type (multiple sires, single sire, or AI). In DFC
      analysis, the same fixed effects were considered excluding the month of last
      calving. For DC, a repeatability animal model was applied. Noncalvers were not
      considered in analyses because an attempt to include them, attributing a penalty,
      did not improve the identification of genetic differences between animals.
      Heritability estimates ranged from 0.04 to 0.06 for DC, from 0.06 to 0.13 for
      DFC, from 0.42 to 0.44 for SC, from 0.06 to 0.08 for AFC, and was 0.30 for W550.
      The genetic correlation estimated between DC and SC was low and negative (-0.10),
      between DC and AFC was high and positive (0.76), and between DC and W550 was
      almost null (0.07). Similar results were found for genetic correlation estimates
      between DFC and SC (-0.14), AFC (0.94), and W550 (-0.02). The genetic correlation
      estimates indicate that the use of DC in the selection of beef cattle may promote
      favorable correlated responses to age at first mating and, consequently, higher
      gains in sexual precocity can be expected.

PMID- 15956459
TI  - Effect of docosahexaenoic acid and arachidonic acid on the expression of
      adipocyte determination and differentiation-dependent factor 1 in differentiating
      porcine adipocytes.
AB  - Adipocyte determination and differentiation-dependent factor 1 (ADD1) drives the
      expression of several lipogenic genes in mammals. Polyunsaturated fatty acids
      decrease ADD1 mRNA abundance in differentiating porcine adipocytes. The current
      study was designed to explore the mechanisms by which PUFA inhibit the expression
      of ADD1 in porcine adipocytes. Porcine preadipocytes were differentiated for 24 h
      with 0 or 100 microM of docosahexaenoic acid (DHA) and mixtures of different
      concentrations of antioxidants to investigate the effect of DHA and antioxidants
      on the ADD1 mRNA abundance. We found the relative mRNA abundance was decreased by
      the addition of 100 microM DHA to the medium for porcine differentiating
      adipocytes, and adding an antioxidant mixture to the medium prevented part of the
      decrease in ADD1 mRNA abundance. These data suggest that DHA decreased the steady
      state transcription factor ADD1 mRNA through a mechanism related to fatty acid
      peroxidation. Indeed, adding 7.5 microM vitamin E (a natural antioxidant) also
      restored the concentrations of ADD1 and fatty acid synthase mRNA, which were
      decreased by DHA treatment; however, the DHA or the antioxidant treatment did not
      change the expression of antioxidation genes (superoxide dismutase 1 and
      glutathione peroxidase 1) in porcine stromal vascular cells. When supplemented
      with the eicosanoid synthesis pathway inhibitors, the inhibition of the
      expression of ADD1 by arachidonic acid was partially recovered. These results
      suggest that the mechanism by which PUFA decrease ADD1 mRNA is due to the
      metabolic product of eicosanoids and peroxidation of these PUFA.

PMID- 15956460
TI  - Carcass composition, bone mechanical properties, and meat quality traits in
      relation to growth rate in rabbits.
AB  - The objective of this study was to characterize correlated responses in carcass
      composition, bone mechanical properties, and meat quality indicators to divergent
      selection for growth rate. Rabbits from low (LOW) or high (HIGH) lines
      divergently selected over five generations on 63-d BW and a control group (CONT)
      were used. Rabbits were slaughtered at an average BW of 2,306 +/- 65 g,
      corresponding to 63, 58, or 52 d of age in LOW (n = 41), CONT (n = 43), and HIGH
      (n = 44) groups, respectively. Postweaning ADG and G:F increased (P < 0.001) in
      the order LOW < CONT < HIGH groups. The lengths of the tibia and femur in rabbit
      legs decreased (P < 0.001) with increasing growth rate. Tibia and femur bone
      intrinsic stiffness, as assessed by a three-point flexure test, followed the
      order (P < 0.001) of HIGH < CONT < LOW groups. At the same BW, HIGH rabbits and
      CONT rabbits showed many similarities for dressing percent, carcass composition,
      and color and chemical composition of muscles or meat parts. In contrast, carcass
      yield and the relative proportion of hind part were 3% greater (P < 0.01) in LOW
      rabbits than in CONT and HIGH rabbits. The meat-to-bone ratio in the hind leg was
      11% greater (P < 0.001) in the LOW group compared with the CONT and HIGH groups.
      Yellow color index and moisture content in LM, a fast-twitch glycolytic muscle,
      were lower (P < 0.05) in LOW rabbits than in HIGH rabbits, but ultimate pH, WHC,
      and cooking loss did not differ between the two growth-selected lines. Ultimate
      pH in semitendinosus, a mixed slow- and fast-twitch oxidoglycolytic muscle, was
      less (P < 0.001) in HIGH rabbits than in CONT and LOW rabbits. However, lactate
      dehydrogenase and isocitrate dehydrogenase activities in this muscle (n = 21 per
      group), assessed at the time of slaughter as markers of glycolytic and oxidative
      capacities, respectively, did not differ among groups. Growth rate did not modify
      mean cross-sectional area and type frequency of myofibers in semitendinosus
      muscle. Finally, Warner-Bratzler shear force and total energy needed to achieve
      rupture did not differ among groups in semitendinosus muscle (n = 21 per group),
      whereas they were the least (P < 0.001) in LM (n = 128) from HIGH rabbits.
      Results from this study indicate that improvement of growth rate by selection has
      little effect in rabbit carcass and meat quality traits.

PMID- 15956461
TI  - Effect of feed withdrawal and handling intensity on longissimus muscle glycolytic
      potential and blood measurements in slaughter weight pigs.
AB  - This study was carried out to evaluate the effect of feed withdrawal and handling
      intensity on blood acid-base responses and muscle glycolytic potential in
      slaughter-weight pigs. Sixty crossbred pigs (BW = 107.7 +/- 0.56 kg; 44 barrows
      and 16 gilts) were used in a randomized complete block design with a 2 x 2
      factorial arrangement of treatments: 1) feed withdrawal (0 vs. 24 h), and 2)
      handling intensity (low vs. high). The high-intensity handling treatment
      consisted of moving the pigs through a passage (12.2 m long x 0.91 m wide) for
      eight laps using an electric goad two times per lap. Pigs in the low-intensity
      handling treatment were moved at their own pace through the passage for eight
      laps using a livestock panel and paddle. Biopsy samples were collected from the
      LM at the beginning of feed withdrawal, at the end of the handling procedure, and
      4 h after handling. Blood samples were collected 2 h before and immediately after
      the handling procedure. There were no interactions between feed withdrawal and
      handling intensity for any of the variables measured. Feed withdrawal decreased
      (P < 0.05) baseline and posthandling body temperature (38.85 vs. 38.65 degrees C;
      SEM = 0.060 and 39.70 vs. 39.37 degrees C; SEM = 0.04, respectively) and blood
      glucose, lowered (P < 0.05) baseline partial pressure of oxygen and partial
      pressure of carbon dioxide, and increased (P < 0.01) baseline and posthandling
      plasma free fatty acid concentrations. High-intensity handling produced higher (P
      < 0.01) posthandling lactate and glucose, and lower (P < 0.01) posthandling blood
      pH (7.33 vs. 7.18 +/- 0.02, respectively), bicarbonate, base excess, and total
      carbon dioxide than low-intensity handling. Longissimus muscle glycolytic
      potential of fasted pigs was lower (P < 0.01) than in fed pigs at the end of the
      handling procedure (177.2 vs. 137.0 micromol/g of wet tissue; SEM = 10.08,
      respectively). There was no effect of handling intensity on longissimus muscle
      glycolytic potential. Feed withdrawal did not attenuate the blood acid-base
      changes caused by handling; however, the combination of feed withdrawal and
      handling decreased muscle glycolytic potential.

PMID- 15956462
TI  - Technical Note: Transcervical deep cornual insemination of goats.
AB  - A newly developed technique for trans-cervical deep uterine insemination of goats
      is described. An experiment was conducted to compare this transcervical method
      with the laparoscopic intrauterine insemination using frozen-thawed semen. Of the
      46 primiparous and 21 multiparous estrus-synchronized Boer goat does inseminated
      transcervically, 71% (22/31) kidded compared with 53% (19/36) of does inseminated
      laparoscopically (P < 0.025). The corresponding litter sizes were 2.27 and 1.89
      (P < 0.01). In another 34 parous does inseminated transcervically without
      preceding hormone treatment, kidding rate and litter size were 71% and 1.76,
      respectively. We conclude that transcervically conducted bilateral deep cornual
      insemination may be considered a viable alternative to laparoscopic insemination.

PMID- 15956463
TI  - Fructooligosaccharide supplementation in the yearling horse: effects on fecal pH,
      microbial content, and volatile fatty acid concentrations.
AB  - Short-chain fructooligosaccharides (FOS) were supplemented to the diets of nine
      quarter horses ranging in age from 489 to 539 d with initial BW averaging 400.6
      +/- 21.2 kg. The objectives of this study were to determine the effects of
      dietary FOS on the fecal responses in terms of pH, the microbial population, and
      VFA concentrations. The horses were used in a 3 x 3 replicated Latin square
      design, fed according to NRC requirements, and their individual diets were
      supplemented with no FOS (CON), 8 g of FOS/d (LOW), or 24 g of FOS/d (HIGH) over
      three 10-d feeding periods. On the last 3 d of each 10-d feeding period, a single
      fecal sample was collected between 0730 and 0930. Fecal pH decreased linearly (P
      = 0.01) from 6.48 with the CON diet to 6.38 with the HIGH diet, but there was no
      change (P = 0.19 for linear effect) in fecal consistency among treatments. A
      quadratic effect (P < 0.01) was observed for fecal Escherichia coli population,
      but no difference (P = 0.88 for linear effect) was found in fecal Lactobacilli
      enumeration among treatments. The presence of fecal Bifidobacteria was unable to
      be confirmed and was therefore not reported. Fecal acetate concentrations
      increased linearly (P = 0.03), with means of 2.13, 2.18, and 2.52 mg/g of wet
      feces for CON, LOW, and HIGH treatments, respectively. Similarly, fecal
      propionate concentrations increased linearly (P = 0.01), with means of 0.58,
      0.64, and 0.73 mg/g for CON, LOW, and HIGH treatments, respectively. Fecal
      butyrate concentrations also increased linearly (P = 0.02), with means of 0.40,
      0.46, and 0.54 mg/g for CON, LOW, and HIGH treatments, respectively. Total VFA (P
      = 0.01) and lactate (P = 0.02) concentrations increased linearly, with total VFA
      means of 3.47, 3.69, and 4.25 mg/g for CON, LOW, and HIGH treatments,
      respectively, and lactate means of 0.36, 0.41, and 0.47 mg/g for CON, LOW, and
      HIGH treatments, respectively. Supplementing FOS in diets fed to yearling horses
      altered fecal microbial populations, fecal VFA concentrations, and pH.

PMID- 15956464
TI  - Effect of feed particle size and feed processing on morphological characteristics
      in the small and large intestine of pigs and on adhesion of Salmonella enterica
      serovar Typhimurium DT12 in the ileum in vitro.
AB  - A 2 x 2 factorial experiment with pigs was undertaken to investigate the effect
      of particle size (fine and coarse) and feed processing (pelleted and nonpelleted)
      on morphological characteristics in the small intestine, cecum, and colon of pigs
      and on the adhesion of Salmonella enterica serovar Typhimurium DT12 to the ileum
      in vitro. Ninety-six pigs (average BW = 33 +/- 7 kg) were fed the experimental
      diets. After 4 wk, 24 pigs were selected (six pigs per diet) and euthanized, and
      tissue samples were taken from the mid and distal small intestine, cecum, and
      distal colon. The effects of particle size and feed processing on villus height
      and crypt depth in the small intestine were minor. Feeding coarse diets increased
      (P = 0.05) the crypt depth in the colon. The crypt depth was 420 +/- 12 and 449
      +/- 12 microm in pigs fed finely and coarsely ground feed, respectively. Pigs fed
      pelleted diets had a larger (P = 0.01) staining area for neutral mucins, as well
      as for acidic and sulfomucins on the villi of the distal small intestine than
      pigs fed nonpelleted diets. The area was 41, 46, and 33% larger for neutral,
      acidic, and sulfomucins, respectively. The mucin-staining areas of the crypts in
      the cecum and the colon were not affected by the experimental diets. Examination
      of lectin binding characteristics of the distal small intestine and the cecum did
      not reveal any differences between the experimental diets. Using a pig intestine
      organ culture model, Salmonella adhered less (P < 0.05) to the ileal tissue of
      pigs fed the nonpelleted diets than to those fed pelleted diets; the adherence
      was 60% less in these pigs. Results of this study suggest that pigs fed pelleted
      diets secrete mucins that are capable of binding Salmonella enterica serovar
      Typhimurium DT12 and thereby allowing for colonization. Therefore, pigs fed a
      nonpelleted diet are better protected against Salmonella infections than pigs fed
      a pelleted diet.

PMID- 15956465
TI  - Technical Note: Improved technique for fitting pigs with steered ileocecal valve
      cannulas.
AB  - Collection of ileal digesta to evaluate AA digestibilities has become
      increasingly important in swine nutrition research. Steered ileocecal valve
      cannulation of pigs permits total collection of ileal digesta, while still
      allowing normal digesta flow during noncollection periods. This technique was
      modified and used with 64 crossbred barrows in five trials. Our procedural
      changes included preoperative i.v. administration of a broad-spectrum antibiotic
      and nonsteroidal antiinflammatory drug, sharp incision through the muscle layers
      of the laparotomy wound, use of a heparinized saline lavage solution, replacement
      of the guide ring with a stylette, and fixing the outer cannula barrel in place
      with a hose clamp. The current technique involves a right flank laparotomy,
      parallel and distal to the last rib, with the pig under general anesthesia. A
      stainless-steel ring (inner ring = 2.0 mm thick, 35.0 mm i.d.) is introduced into
      the ileal lumen through an enterotomy proximal to the origin of the ileocecal
      fold. A nylon string attached to this ring is threaded through the ileum and
      ileocecal valve into the cecum using a silastic stylette, which encases the
      string. A second stainless-steel ring (outer ring = 2.0 mm thick, 34 mm o.d.) is
      fixed in place around the ileum, distal to the inner ring and just proximal to
      the ileocecal valve. A polyurethane cannula barrel (barrel = 100 mm long, 26 mm
      i.d., 32 mm o.d.; flange = 70 mm o.d.) is introduced into the cecal lumen via an
      enterotomy through the lateral cecal band and secured in place with two purse
      string sutures. The cannula is exteriorized through an incision caudal and
      proximal to the intial laparotomy site, where it is plugged using a cylindrical
      stopper (26 mm o.d., 55 mm long) and held in place by a second cannula barrel
      (barrel = 43 mm length, 33 mm i.d., 41 mm o.d.; flange = 80 mm o.d.). Procedural
      changes decreased postsurgical complications, as evidenced by decreased seepage
      around the cannula and fewer and less severe adhesions noted at necropsy. Based
      on five trials, this technique is a reliable means of collecting ileal digesta
      for nutrient analyses.

PMID- 15956466
TI  - Influence of supplemental magnesium, tryptophan, vitamin C, and vitamin E on
      stress responses of pigs to vibration.
AB  - Our objectives were to investigate and compare the effects of supplemental Mg,
      Trp, vitamin E (vit E), and vitamin C (vit C) on stress responses of pigs
      undergoing transport simulation. In this study, 126 pigs (25.1 +/- 4.4 kg BW)
      were allocated to one of the six following treatments: 1) negative control (no
      supplementation); 2) positive control (i.m. injection with 0.5 mg of carazolol/20
      kg BW 12 h before vibration, beta-blocker); 3) Trp (additional amount of 6 g/kg
      of feed for 5 d, as-fed basis); 4) Mg (3 g/L drinking water for 2 d); 5) vit E
      (additional amount of 150 mg/kg of feed for 21 d, as-fed basis); 6) or vit C
      (additional amount of 300 mg/kg of feed for 21 d, as-fed basis). Pigs were
      treated in groups of three, and each treatment was replicated seven times. Feed
      and water intake were not different among treatments. Heart rate variables (mean,
      peak, and minimum heart rate, ventricular ectopic beats, and ST elevation of
      Channels A and B) and heart rate variability were registered from the night
      before vibration. Pigs were subjected to vibration in a transport simulator (8
      Hz, 3 m/s) for 2 h and allowed to recover for 2 h. Generally, the positive
      control pigs had the lowest heart rate values (mean, peak, minimum heart rate, ST
      elevation of Channel A; P < 0.05), whereas Mg and Trp decreased ventricular
      ectopic beats and ST elevation of Channel B, respectively. The effect of vit C
      and E as vagal stimulators was clearly visible, whereas carazolol and Mg clearly
      blocked the sympathetic pathways of the autonomic nervous system. During
      vibration, the negative control pigs lay the least, and Mg pigs the most (P <
      0.05). Salivary cortisol concentrations (taken before and after vibration and
      after recovery) showed that vit E pigs produced the least cortisol during stress
      periods. Intermediary metabolites (glucose, lactate, creatine kinase, and NEFA)
      were analyzed in plasma from blood taken before and after vibration. At the two
      sampling points, the vit E and Mg pigs had the lowest NEFA concentrations (P <
      0.05), and the vit E pigs also had the lowest lactate concentrations before
      vibration. Urine samples were collected before and after vibration to determine
      catecholamine concentrations; only negative control pigs had an increase (P =
      0.04) in epinephrine concentration, despite large individual variation. In
      general, these results indicate that the supplementation of Trp, Mg, vit E, or
      vit C improved coping ability of pigs during vibration comparison with the
      negative control treatment. A muscular injection of carazolol influenced only the
      heart rate variables.

PMID- 15956467
TI  - Performance of growing-finishing pigs fed diets containing YieldGard Rootworm
      corn (MON 863), a nontransgenic genetically similar corn, or conventional corn
      hybrids.
AB  - Two studies were conducted at two locations to evaluate growth performance and
      carcass characteristics of growing-finishing pigs fed diets containing either
      YieldGard Rootworm corn (MON 863), a non-transgenic genetically similar corn
      (RX670), or two conventional nontransgenic corn hybrids (DK647 and RX740). A
      randomized complete block design with a 2 x 4 factorial arrangement of treatments
      (two genders and four corn hybrids) was used. Study 1 used 72 barrows and 72
      gilts (progeny of Danbred sires x [Danbred x NE White line] dams grown from 22.7
      to 117.0 kg BW). Pigs were housed in a modified open-front building in single
      gender groups of six (six pens per dietary treatment). Study 2 used 80 barrows
      and 80 gilts (progeny of PIC 337 sires x C22 dams) grown from 29.5 to 114.9 kg
      BW. Pigs were housed in an environmentally controlled finishing building in
      single-gender groups of five (eight pens per dietary treatment). The test corns
      were included at a fixed proportion of the diet in both studies. Animals had ad
      libitum access to feed and water. Pigs were slaughtered at the end of the growth
      period using standard procedures, and carcass measurements were taken. There were
      no diet x gender interactions for growth performance or carcass measurements in
      either study. In both studies, overall ADG, ADFI, and G:F were not affected by
      corn hybrid. There was no effect of corn hybrid on carcass or LM quality
      measurements in Study 1. In Study 2, LM protein content was less (P< 0.05) for
      pigs fed RX740 compared with those fed either MON 863 or RX670; however, there
      was no effect of corn hybrid on other LM composition measures or on quality
      traits. In both studies, differences between barrows and gilts for growth and
      carcass traits were similar to previous research. These results suggest that the
      YieldGard Rootworm corn (MON 863) results in equivalent growth performance and
      carcass quality to nontransgenic corn hybrids in growing-finishing pigs.

PMID- 15956468
TI  - Models for estimating parameters of neutral detergent fiber digestion by ruminal
      microorganisms.
AB  - Model assumptions included number of concurrently degrading entities (or pools)
      and expected distributions of undegraded NDF. Degradation processes modeled
      included a single pool with ruminal age-constant rates (exponential
      distribution), a single pool with a ruminal age-dependent rate, two pools with
      age-constant rates, two pools with age-dependent and age-constant rates, and a
      continuum of pools with a gamma distribution of age-constant rates. Various sizes
      of ingestively masticated fragments of bermudagrass hay or corn silage were
      obtained via wet sieving of esophageal masticate and incubated in vitro with
      ruminal fluid for 0 h, every 6 h up to 48 h, and every 12 h up to 168 h. Models
      assuming a single pool of age-constant or age-dependent rates had larger mean
      residual mean squares (P < 0.05) than did the gamma mixture model or the two-pool
      models. Degradation rates estimated by the gamma mixture model indicated
      distribution of rates ranging from near exponential, age-constant distribution to
      a near normal bell-shaped distribution of age-constant rates for different
      datasets. Superior fit by the two-pool models in most datasets (83%) indicated
      that having two resolvable entities of potentially degradable NDF with different
      degradation rates was causal of a biphasic distribution of lifetimes. Increasing
      order of age-dependency modeled in the two-pool model improved fit and precision
      of estimation (standard error of estimate) for the limit parameters of time delay
      and indigestible NDF. Both the gamma mixture continuum of age-constant rate model
      and the two-pool, age-dependent models with a discrete time delay provided
      similar fit to data and flexibility for fitting data with lifetime distributions
      ranging from simple exponential to sigmodial. The two-pool, age-dependent and
      gamma-distributed, age-constant models were better in fitting the dominant
      biphasic lifetime distributions that occurred when the two pools of degrading
      entities were of similar size and in estimating the discrete time delay when
      strategic, quality data were available. Having fewer parameters (four), the gamma
      distributed, age-constant model was superior when data quality was limited.

PMID- 15956469
TI  - Effects of size of ingestively masticated fragments of plant tissues on kinetics
      of digestion of NDF.
AB  - Ingestively masticated fragments were collected and sized via sieving. Different
      sizes of esophageal masticate and ruminal digesta fragments, and ground fragments
      of larger masticated pieces were incubated in vitro, and undigested NDF remaining
      at intervals of up to 168 h of incubation was determined. The ruminal age
      dependent time delay (tau) for onset of digestion of NDF was positively
      correlated (P < 0.004) with the mean sieve aperture estimated to retain 50% of
      the fragments between successive sieve apertures (MRA). Degradation rate of
      potentially degradable NDF (PDF) and level of indigestible NDF were not related
      (P > 0.10) to MRA of masticated and ground fragments. Estimates of tau were
      positively related to MRA, with slopes of bermudagrass < corn silage < ruminal
      fragments of corn silage. It was concluded that fragment size-, and consequently,
      ruminal age-dependent onset of PDF degradation of a mixture of different fragment
      sizes results in an age-dependent rate of degradation of the more rapidly
      degrading of two subentities of PDF. Models are proposed that assume a tau before
      onset of simultaneous degradation of PDF from two pools characterized as having
      gamma-modeled age-dependency and age-constant rates. The ruminal age-dependent
      pool seems to be associated with the faster-degrading pool, and its rate
      parameter increases with range in MRA in the population of fragments.
      Conceptually, the ruminal age-dependent rate parameter for PDF degradation seems
      to represent a composite of several effects: 1) effects of the size-dependent
      tau; 2) range in MRA of the population of ingestively masticated fragments; and
      3) subentities of PDF that degrade via more rapid age-dependent rates compared
      with subentities of PDF that degrade via age-constant rates. The estimated
      fractional rates of ruminative comminution of ingestively masticated fragments
      (0.060 to 0.075/h) were of a magnitude similar to the mean fractional rates of
      PDF digestion (0.030 to 0.085/h), which implies that ruminative comminution may
      be first-limiting to fractional rate of PDF digestion. The in vivo roles of
      ingestive and ruminative mastication of fragments on PDF degradation must be
      considered in any kinetic system for estimating PDF digestion in the rumen. These
      results and others in the literature suggest that the rate of surface area
      exposure rather than intrinsic chemical attributes of PDF may be first-limiting
      to degradation rate of PDF in vivo.

PMID- 15956470
TI  - Changes in ruminal fermentation and protein degradation in growing Holstein
      heifers from 80 to 250 kg fed high-concentrate diets with different forage-to
      concentrate ratios.
AB  - Six Holstein heifers (initial BW = 65.2 +/- 1.8 kg) fitted with ruminal cannulas
      were used in a repeated measures trial to assess the effect of age and forage-to
      concentrate ratio on ruminal fermentation end products and in situ degradation
      kinetics of four plant protein supplements (soybean meal, sunflower meal, peas,
      and lupin seeds). Alfalfa hay also was incubated in situ to estimate NDF
      degradation. Three experimental periods were conducted at 13, 27, and 41 wk of
      age. Heifers were fed one of two diets, 12:88 vs. 30:70 forage-to-concentrate
      ratio (DM basis), offered as total mixed ration on an ad libitum basis. Intakes
      of DM, OM, CP, NDF, and ADG were not affected (P > or = 0.105) by diet. The 30:70
      diet resulted in faster (P = 0.045) fluid passage rate and decreased (P = 0.015)
      ammonia N concentration compared with the 12:88 diet, but no differences (P > or
      = 0.244) were detected in ruminal pH and total VFA concentration between diets.
      The rate of degradation and the effective degradability of N in protein
      supplements was greater with the 30:70 diet for peas (P < or = 0.008) and lupin
      seeds (P < or = 0.02), and in the 12:88 diet for sunflower meal (P < or = 0.06).
      Degradation of NDF of alfalfa hay was low with both diets (18.5 and 23.7 % for
      12:88 and 30:70, respectively); however, the rate and extent of DM and NDF
      degradation were greater (P < or = 0.016) with the 30:70 diet, suggesting a
      higher cellulolytic activity. Total VFA concentration and the proportion of
      propionate increased (P < or = 0.035), and the acetate proportion decreased (P =
      0.021) with age. Average pH, ammonia N concentration, and passage rates were not
      affected (P > or = 0.168) by age. Degradation rate and effective degradability of
      N of sunflower meal, peas, lupin seeds, and of DM of alfalfa hay increased (P <
      or = 0.08) with age, but degradation kinetics of NDF of alfalfa hay was not
      affected (P > or = 0.249). The increase in the rate and extent of N degradation
      with age would suggest an increase in proteolytic activity, and the changes in
      the fermentation pattern may reflect an increase in amylolytic activity caused
      mainly by an increase in the gross intake of nonstructural carbohydrates and by
      adaptation of ruminal microflora after long exposure to these nutrients.

PMID- 15956471
TI  - Effects of choline on blood metabolites associated with lipid metabolism and
      digestion by steers fed corn-based diets.
AB  - Ruminally cannulated steers (281 +/- 18 kg) were used to evaluate effects of
      choline on digestion and metabolism. Four steers were implanted with 24 mg of
      estradiol and 120 mg of trenbolone acetate, and four steers were not implanted.
      Cattle were assigned to concurrent 4 x 4 Latin squares. Dietary treatments were a
      2 x 2 factorial: 0 or 4% tallow (DM basis) in corn-based diets, and 0 or 5 g/d
      supplemental choline administered abomasally. Blood collected before and 6 h
      after the initial choline infusion was used to assess acute responses to choline.
      Digestibility and blood metabolites were measured after adaptation to choline, as
      well as after an abomasal dose of 100 g of lipid. Digestibilities of dietary DM
      (P = 0.29) and of dietary total fatty acids (P = 0.42) were not affected by
      choline. Apparent digestibilities of C18:0 and C18:1 fatty acids were greater (P
      < 0.05) when diets contained 4% tallow. Digestibilities of fatty acids in the
      lipid dose were less than those in the diet, and no biologically important
      differences in fatty acid disappearance resulted from the treatments. No
      significant acute responses to choline were detected. After adaptation to
      choline, no important differences in plasma metabolites occurred in response to
      choline infusion. Plasma urea was less (P < 0.05) for implanted cattle,
      reflecting increased deposition of protein. Plasma cholesterol was greater (P <
      0.05) for steers fed 4% tallow. Changes in plasma triglycerides in response to an
      abomasal lipid dose were less (P < 0.05) for steers fed 4% tallow, probably due
      to greater triglyceride concentrations at the time of lipid dosing. In summary,
      few responses to abomasally infused choline were observed in either digestion or
      plasma metabolites.

PMID- 15956472
TI  - Effects of dietary magnesium and short-duration transportation on stress
      response, postmortem muscle metabolism, and meat quality of finishing swine.
AB  - Crossbred pigs, heterozygous for the halothane gene, were used to determine the
      effects of long-term dietary supplementation of magnesium mica (MM) and short
      duration transportation stress on performance, stress response, postmortem
      metabolism, and pork quality. Pigs were blocked by weight, penned in groups (six
      pigs per pen), and pens (three pens per diet) were assigned randomly either to a
      control corn-soybean meal diet or the control diet supplemented with 2.5% MM (as
      fed basis; supplemented at the expense of corn). Diets were fed during the early
      finisher (0.95% lysine, as-fed basis; 43.7 to 68 kg) and late-finisher (0.85%
      lysine, as-fed basis; 68 to 103 kg) periods. At the conclusion of the 71-d
      feeding trial, 12 pigs from each dietary treatment were selected randomly and
      subjected either to no stress (NS) or 3 h of transportation stress (TS). Dietary
      MM had no effect (P > or = 0.40) on ADG or ADFI; however, G:F was improved (P <
      0.05) during the early-finisher period when pigs were fed MM-supplemented diets.
      Plasma glucose concentrations were increased in TS pigs fed the control diet, but
      transportation did not affect plasma glucose in pigs fed 2.5% MM (diet x
      transportation stress; P = 0.02). Dietary MM did not affect blood lactate,
      cortisol, insulin, NEFA, Ca, or Mg concentrations in response to TS (diet x
      transportation stress; P > or = 0.13); however, circulating lactate, cortisol,
      and glucose concentrations increased in TS pigs (transportation stress x time; P
      < 0.01). The LM from TS pigs fed MM had higher initial (0-min) and 45-min pH
      values than the LM from NS pigs fed the control diet (diet x transportation
      stress x time; P = 0.07). Lactic acid concentration and glycolytic potential were
      greater in the LM of TS pigs fed MM than TS pigs fed control diets (diet x
      transportation stress; P < or = 0.01). Although some trends were identified,
      neither MM (P > or = 0.15) nor TS (P > or = 0.11) altered the color or water
      holding capacity of the LM and semimembranosus. The transportation model elicited
      the expected changes in endocrine and blood metabolites, but dietary MM did not
      alter the stress response in pigs. Conversely, although pork quality traits were
      not improved by dietary MM, delaying postmortem glycolysis and elevating 0- and
      45-min muscle pH by feeding finishing diets fortified with MM may benefit the
      pork industry by decreasing the incidence of PSE pork in pigs subjected to short
      duration, routine stressors.

PMID- 15956473
TI  - Calpain 3/p94 is not involved in postmortem proteolysis.
AB  - Studies on the correlation between expression and/or autolysis of calpain and
      postmortem proteolysis in muscle have provided conflicting evidence regarding the
      possible role of calpain 3 in postmortem tenderization of meat. Thus, the
      objective of this research was to test the effect of postmortem storage on
      proteolysis and structural changes in muscle from normal and calpain 3 knockout
      mice. Knockout mice (n = 6) were sacrificed along with control mice (n = 6). Hind
      limbs were removed and stored at 4 degrees C; muscles were dissected at 0, 1, and
      3 d postmortem and subsequently analyzed individually for degradation of desmin.
      Pooled samples for each storage time and mouse type were analyzed for degradation
      of nebulin, dystrophin, vinculin, and troponin-T. In a separate experiment, hind
      limb muscles from knockout (n = 4) and control mice (n = 4) were analyzed for
      structural changes at 0 and 7 d postmortem using light microscopy. As an index of
      structural changes, fiber detachment, cracked or broken fibers, and the
      appearance of space between sarcomeres were quantified. Cumulatively, the results
      of the first experiment indicated that postmortem proteolysis of muscle occurred
      similarly in control and in calpain 3 knockout mice. Desmin degradation did not
      differ (P > 0.99), and there were no indications that degradation of nebulin,
      dystrophin, vinculin, and troponin-T were affected by the absence of calpain 3 in
      postmortem muscle. Structural changes were affected by time postmortem (P <
      0.05), but not by the absence of calpain 3 from the muscles. In conclusion, these
      results indicate that calpain 3 plays a minor role, if any, in postmortem
      proteolysis in muscle.

PMID- 15956474
TI  - Repeated handling of pigs during rearing. I. Refusal of contact by the handler
      and reactivity to familiar and unfamiliar humans.
AB  - Pigs housed in groups received different handling treatments for 40 d until
      slaughter age. Pigs of the human interaction (HI) and refusal of contact (RC)
      groups were individually introduced into a pen each day, where they remained for
      3 min in the presence of a squatted handler. The handler tried to increase
      progressively physical reciprocal interactions with the HI pigs using eye and
      body contact and voice. The handler remained immobile and avoided eye contact and
      use of voice with RC pigs. These pigs were pushed away when they touched the
      handler. Control pigs remained in their home pens. Over sessions, HI pigs
      progressively increased physical interactions with the handler, up to 35% of
      their time. The RC pigs were motivated to interact with the handler as they tried
      to establish physical contact with the handler throughout the experiment. They
      increased levels of locomotion, rubbing, immobility, and snout contact with the
      wall, suggesting that they were frustrated by the refusal of contact. At the end
      of the experimental period, all pigs were subjected to three human exposure
      tests, where pigs were exposed to the handler and two other persons, one of which
      was unfamiliar, in a Latin square design. During this test, behavior of the
      humans was the same as for the RC treatment. The HI pigs discriminated between
      the handler and the other persons as indicated by their increased approach
      behavior towards the handler. Part of the prior handling experience was
      generalized to other humans as indicated by higher levels of proximity of HI and
      RC pigs with the different persons compared with controls. Physical contact with
      the human was associated with increased heart rates. Two possibilities are that
      these two characteristics are part of a general behavioral/physiological reactive
      profile, or that contact with humans provokes an arousal or emotional response.
      Despite this, behavioral data show that pigs are motivated to be in physical
      contact with a handler, even when the handler consistently refuses contact.

PMID- 15956475
TI  - Repeated handling of pigs during rearing. II. Effect of reactivity to humans on
      aggression during mixing and on meat quality.
AB  - The present study was designed to determine whether reactivity toward humans can
      be used to predict a pig's reactivity to the slaughter procedure as measured by
      postmortem muscle metabolism. Forty-two pigs were group-reared in six pens with
      straw-bedding. Pigs received regular positive (HI) or mildly negative (RC)
      handling training in a separate pen for 40 d before slaughter. Control pigs
      remained in their home pens throughout rearing. Pigs were slaughtered at a
      commercial packing plant, and half of each treatment group (HI, RC, or controls)
      was accompanied by the handler throughout mixing and transportation, as well as a
      portion of the lairage time and introduction to the holding pens situated before
      the slaughter room, whereas the other half was not accompanied by the handler.
      Muscle pH and temperature, objective color (L*, a*, and b* values), and drip loss
      were measured on the LM, biceps femoris, semimembranosus, and adductor femoris.
      Prior handling experience did not in itself influence ultimate meat quality (P >
      0.37); however, the presence of the negative handler (RC pigs) at slaughter
      accelerated (P < 0.06) preslaughter glycogen breakdown in the LM. Fighting
      behavior during mixing explained between 13 and 32% of the variability of
      lightness (L* values) of the LM, biceps femoris, and semimembranosus. Visual
      contact with the handler at the start of the handling training and number of
      fights initiated explained between 31 and 42% of the variability in ultimate
      muscle pH. Latency to approaching the handler during human exposure tests
      explained 20% of the variability in initial muscle temperature of two muscles.
      Fighting behavior during mixing could be partly predicted from fighting during a
      food competition test conducted at the start of the rearing period. Results
      indicate that reactivity to humans and the tendency to fight determined, in part,
      meat quality in pigs of similar genetic and rearing backgrounds. These behavioral
      characteristics were, to some extent, determined early in life. Handling
      experience modified behavior toward the handler but correlations between
      behavioral characteristics and meat quality were not influenced by prior handling
      experience.

PMID- 15956476
TI  - Concentrations of fecal bacteria and nutrients in soil surrounding round-bale
      feeding sites.
AB  - An experiment was conducted over 7 mo (January to July 2003) to evaluate fecal
      bacteria and nutrient concentrations in soil surrounding round-bale feeders at 10
      winter feeding sites. Soil samples 15 cm in depth were taken monthly from each
      site at distances of 3, 12, 21, and 30 m from the feeder. Soil samples were taken
      before livestock access to the sites (January), during the feeding period
      (February, March, and April), and after cattle removal from the sites (May, June,
      and July). Results indicated that fecal bacteria concentrations increased over
      the feeding period and were greatest at close proximity to round-bale feeders.
      Fecal Escherichia coli concentrations were greater in April (P < 0.03) at 3 and
      12 m than in all other months, except March. At 21 and 30 m from the feeders,
      fecal E. coli concentrations were greater in April (P < 0.01) than in other
      months. At 3 m from the feeder, fecal Streptococci concentrations were greater in
      March and April (P < 0.01) than in other months. Although fecal E. coli
      concentrations in July had returned to levels similar to those in the prefeeding
      period, fecal Streptococci remained at higher concentrations (P < 0.05) than at
      the prefeeding period. The concentration of soil P at 3 m was greater in April (P
      < 0.02) than in January, February, and May. After cattle access to the sites,
      soil DM content was consistently less for samples taken at 3 m from the feeder
      compared with the other distances, with quadratic decreases (P < 0.02) noted in
      March, April, and July, and linear decreases (P < 0.01) in May and June, as
      distance from the feeder decreased.

PMID- 15956477
TI  - Influence of body weight, age, and weight gain on fertility and prolificacy in
      four breeds of ewe lambs.
AB  - Breeding ewes to lamb at 1 yr of age can improve profitability for some
      production systems. The first objective of this study was to evaluate the effect
      of age and weight at breeding and total postweaning weight gain on reproductive
      performance of ewe lambs. The second objective was to compare the effects of
      weight and age variables in four major sheep breeds (Columbia, Polypay,
      Rambouillet, and Targhee). Weights, ages, and the binary traits of fertility
      (pregnant or nonpregnant) and prolificacy (one lamb born vs. two or more) were
      collected on 2,055 ewe lambs at the U.S. Sheep Experiment Station, Dubois, ID,
      from 1984 through 1988. The effects of age and weight at breeding and total
      weight gain from weaning to breeding on fertility and prolificacy were analyzed
      with a logit model in a maximum likelihood analyses. Differences (P < 0.001)
      among breeds for fertility were identified, with a 93% fertility rate for Polypay
      ewe lambs compared with lower fertility rates in Columbia, Targhee, and
      Rambouillet ewe lambs (50, 60, and 75%, respectively). The percentage of multiple
      births (prolificacy rate) also was higher (P < 0.001) in the Polypay (47%) than
      in Columbia, Targhee, and Rambouillet breeds (1, 13, and 14%, respectively).
      Averaged across breeds, weight at breeding had a positive effect on fertility and
      prolificacy (P < 0.001), whereas total weight gain from weaning to breeding had a
      positive effect only on fertility (P < 0.027). In separate analyses for each
      breed, increasing age (P < 0.001) and weight at breeding (P < 0.001) increased
      the probability of pregnancy in Rambouillet ewe lambs. The probability of
      pregnancy for Targhee ewe lambs increased (P < 0.005) with weight at breeding.
      Increasing weight at breeding increased (P < 0.004) the probability of multiple
      births in all breeds. Increasing total postweaning weight gain increased (P <
      0.007) the probabilities of multiple births in Rambouillet and Targhee ewe lambs.
      In conclusion, Polypay ewe lambs were superior in fertility and prolificacy to
      Columbia, Rambouillet, and Targhee under Western range conditions. Improved
      reproductive performance of Columbia, Rambouillet, and Targhee ewe lambs may be
      achieved by increasing age and weight at breeding and postweaning gain.

PMID- 15956478
TI  - Effect of P.G. 600 on the timing of ovulation in gilts treated with altrenogest.
AB  - We previously reported that ovulation rate, but not pregnancy rate or litter size
      at d 30 after mating, was enhanced by treatment with P.G. 600 (400 IU of PMSG and
      200 IU of hCG, Intervet America, Inc., Millsboro, DE) in gilts fed the orally
      active progestin, altrenogest (Matrix, Intervet America, Inc.) to synchronize
      estrus. We hypothesized that in addition to increasing ovulation rate, P.G. 600
      may have altered the timing of ovulation. Therefore, mating gilts 12 and 24 h
      after first detection of estrus, as is common in the swine industry, may not have
      been the optimal breeding regimen, and as a consequence, pregnancy rate and
      litter size were not altered. The objective of the present study was to determine
      the effect of P.G. 600 on the timing of ovulation in gilts treated with
      altrenogest. Randomly cycling, crossbred gilts (5.5 mo old, 117 kg BW, and 14.7
      mm of backfat) were fed a diet containing altrenogest (15 mg/d) for 18 d. Twenty
      four hours after altrenogest withdrawal, gilts received i.m. injections of P.G.
      600 (n = 25) or saline (n = 25). Gilts were checked for estrus at 8-h intervals.
      After first detection of estrus, transrectal ultrasonography was performed at 8-h
      intervals to determine the time of ovulation. Gilts were killed 9 to 11 d after
      the onset of estrus to determine ovulation rate. All gilts displayed estrus by 7
      d after treatment with P.G. 600 or saline. Compared with saline, P.G. 600
      increased (P = 0.07) ovulation rate (14.8 vs. 17.5, respectively; SE = 1.1). The
      intervals from injection to estrus (110.9 vs. 98.4; SE = 2.7 h; P < 0.01) and
      injection to ovulation (141.9 vs. 128.6; SE = 3.2 h; P < 0.01) were greater in
      gilts treated with saline than in gilts treated with P.G. 600. Duration of estrus
      (54.4 vs. 53.7; SE = 2.5 h), the estrus-to-ovulation interval (30.2 vs. 31.7; SE
      = 2.2 h), and the time of ovulation as a percentage of estrus duration (55.8 vs.
      57.5; SE = 3.0%) did not differ for the P.G. 600 and saline-injected gilts,
      respectively. In summary, P.G. 600 advanced the onset of estrus and ovulation
      following termination of altrenogest treatment and increased ovulation rate;
      however, treatment of gilts with P.G. 600 had no effect on the timing of
      ovulation relative to the onset of estrus.

PMID- 15956479
TI  - Behavior, physiology, and performance of bulls mixed at the onset of finishing to
      form uniform body weight groups.
AB  - In some production settings, beef bulls are mixed at the beginning of the
      finishing period to obtain homogeneous groups to facilitate finishing and to
      produce more homogeneous carcasses. Given the stress induced by mixing, we
      questioned whether this practice was profitable. Sixty-four young bulls were
      finished in groups of four over 8 mo. They were either mixed or unmixed and had
      either homogeneous vs. heterogeneous BW at the beginning of finishing. Behavioral
      traits (social behavior following mixing and general activities during the
      finishing period), stress measurements (cortisol concentration, adrenal weight,
      catecholamine-synthesizing enzyme activity, and pain sensitivity), and production
      traits (growth rate, homogeneity, feed efficiency, and carcass measurements) were
      evaluated. Bulls reacted to the mixing with increased frequency of social
      interactions (agonistic interactions: 17.9 in mixed vs. 1.2 in unmixed bulls, P <
      0.001; sexual interactions: 9.6 vs. 1.7, P < 0.001; nonagonistic interactions:
      5.25 vs. 3.1, P < 0.05). Agonistic and sexual interactions were more frequent
      between bulls of homogeneous BW (P < 0.05). Throughout the finishing period, the
      synchronization of activity tended to be lower between mixed bulls (P = 0.09). At
      slaughter, the activity of tyrosine hydroxylase, a catecholamine-synthesizing
      enzyme, was increased in mixed bulls (1.52 vs. 1.16 nmol.h(-1).mg(-1), P < 0.05),
      which may indicate chronic stress. No differences were noted in ADG or carcass
      traits among treatments. The variability of BW within groups increased in groups
      that were initially homogeneous, whereas it decreased in groups that were
      initially heterogeneous. In conclusion, mixing young beef bulls at the beginning
      of the finishing period did not have detrimental effects on health and
      production, but mixing induced stress, perhaps due to decreased cohesion within
      groups. Thus, we failed to confirm the proposed benefit of mixing bulls to
      homogenize their BW at the onset of finishing because BW homogeneity within
      groups was not maintained throughout the finishing period.

PMID- 15956480
TI  - Effects of varying energy intake and sire breed on duration of postpartum
      anestrus, insulin like growth factor-1, and growth hormone in mature crossbred
      cows.
AB  - Objectives of this study were to evaluate effects of seven sire breed groups and
      three levels of daily ME intake (DMEI = 132 or 189 kcal ME/kg BW(0.75) or ad
      libitum), beginning 5 mo prepartum, on BCS, length of postpartum anestrus, and
      circulating concentrations of IGF-1 and GH in F1 cows (six to eight cows per sire
      breed in each DMEI group) out of Angus or Hereford dams. At the initiation of the
      study, BW were 522, 530, 548, 572, 575, 577, and 595 kg for cows sired by
      Longhorn, Galloway, 1960s Hereford or Angus, 1980s Hereford or Angus, or Nellore,
      Salers, and Shorthorn bulls, respectively (SE = 13; P < 0.001 for sire breed).
      After 4 mo on DMEI treatment during the pre-partum period, cows fed 132 kcal of
      ME/kg BW(0.75)gained little to no BW; cows fed 189 kcal ME/kg BW(0.75) gained 50
      kg; and cows fed ad libitum gained 70 kg (all groups differ P < 0.05).
      Concentrations of progesterone in weekly blood samples collected 2 to 14 wk after
      calving were used to establish when normal luteal function resumed to predict
      length of postpartum anestrus. Length of anestrus was affected by level of DMEI
      in cows sired by Galloway, Longhorn, and Nellore bulls, but not other breeds (P <
      0.02 for interaction of sire breed and DMEI). Level of DMEI, but not sire breed,
      affected (P < 0.01) BCS at wk 2 postpartum. Concentrations of IGF-1 at wk 2
      postpartum differed (P < 0.001) due to sire breed, and changes in concentrations
      of IGF-1 from wk 2 to 14 were influenced (P < 0.03) by the interaction of sire
      breed and level of DMEI; which was primarily the result of differences in rate of
      decrease over time among different sire breed x level of DMEI groupings.
      Concentrations of GH did not differ due to sire breed but varied (P < 0.001) due
      to the interaction of DMEI and week postpartum, for which concentrations of GH
      did not differ at wk 2 but increased over time at rates that were inversely
      proportional to level of DMEI. Length of anestrus was negatively associated (P <
      0.05) with day of calving, BCS, and BW. When effects of sire breed and level of
      DMEI were accounted for (residual correlation), length of anestrus was inversely
      associated (P < 0.01) with IGF-1 concentrations. Breed of sire influenced length
      of postpartum anestrus and energy balance, as predicted by IGF-1, in crossbred
      cows fed varying levels of DMEI.

PMID- 15956481
TI  - Influence of protein supplementation frequency on cows consuming low-quality
      forage: performance, grazing behavior, and variation in supplement intake.
AB  - The objectives of this research were to determine the influence of protein
      supplementation frequency on cow performance, grazing time, distance traveled,
      maximum distance from water, cow distribution, DMI, DM digestibility, harvest
      efficiency, percentage of supplementation events frequented, and CV for
      supplement intake for cows grazing low-quality forage. One hundred twenty
      pregnant (60 +/- 45 d) Angus x Hereford cows (467 +/- 4 kg BW) were used in a 3 x
      3 Latin square design for one 84-d period in each of three consecutive years.
      Cows were stratified by age, BCS, and BW and assigned randomly to one of three
      810-ha pastures. Treatments included an unsupplemented control (CON) and
      supplementation every day (D; 0.91 kg, DM basis) or once every 6 d (6D; 5.46 kg,
      DM basis) with cottonseed meal (CSM; 43% CP, DM basis). Four cows from each
      treatment (each year) were fitted with global positioning system collars to
      estimate grazing time, distance traveled, maximum distance from water, cow
      distribution, and percentage of supplementation events frequented. Collared cows
      were dosed with intraruminal n-alkane controlled-release devices on d 28 for
      estimation of DMI, DM digestibility, and harvest efficiency. Additionally, Cr2O3
      was incorporated into CSM on d 36 at 3% of DM for use as a digesta flow marker to
      estimate the CV for supplement intake. Cow BW and BCS change were greater (P < or
      = 0.03) for supplemented treatments compared with CON. No BW or BCS differences
      (P > or = 0.14) were noted between D and 6D. Grazing time was greater (P = 0.04)
      for CON compared with supplemented treatments, with no difference (P = 0.26) due
      to supplementation frequency. Distance traveled, maximum distance from water, cow
      distribution, DMI, DM digestibility, and harvest efficiency were not affected (P
      > or = 0.16) by protein supplementation or supplementation frequency. The
      percentage of supplementation events frequented and the CV for supplement intake
      were not affected (P > or = 0.58) by supplementation frequency. Results suggest
      that providing protein daily or once every 6 d to cows grazing low-quality forage
      increases BW and BCS gain, while decreasing grazing time. Additionally, protein
      supplementation and supplementation frequency may have little to no effect on cow
      distribution, DMI, and harvest efficiency in the northern Great Basin.

PMID- 15956482
TI  - Estimation of feeding value of four tropical forage species at two stages of
      maturity.
AB  - The feeding value of four tropical grasses was assessed through voluntary intake
      and digestibility studies using yearling Brahman x British steers (average BW =
      256 +/- 34 kg). The digestibility of OM was estimated using total fecal
      collection (TFC), in vitro OM digestibility (IVOMD), and by estimating fecal
      production using insoluble acid detergent fiber (IADF) as an indigestible marker.
      The four grasses consisted of bahiagrass (Paspalum notatum), limpograss
      (Hemarthria altissima), bermudagrass (Cynodon dactylon), and stargrass (Cynodon
      spp.). Grass was harvested at two stages of maturity (approximately 4 and 10 wk).
      Forages were ground (5 to 10 cm) and offered to steers ad libitum. Forage
      treatments were assigned randomly to steers over eight 28-d periods and repeated
      over two consecutive years. Total forage offered and refused was determined
      during a 14-d sample collection period. For determination of fecal output, steers
      were placed into metabolism crates for 7 d. Composited samples of forage offered,
      forage refused, and feces of each steer at each period were analyzed for DM, OM,
      NDF, ADF, IADF, IVOMD, and CP. All digestibility results were calculated on an OM
      basis. There were year x grass x maturity interactions (P < 0.01) for all
      measures of forage quality, except CP. Increased maturity resulted in a 37.8%
      decrease (P < 0.001) in CP concentration when averaged across all forages. Four
      week bermudagrass contained the greatest (P < 0.05) concentration of CP compared
      with all other grasses at both maturities, except 4-wk stargrass. Bahiagrass
      IVOMD did not differ among 4- and 10-wk maturities in both years; however, the
      IVOMD content of both stargrass and bermudagrass decreased (P < 0.05) when these
      forages matured from 4 to 10 wk. Apparent OM digestibility, determined by TFC,
      was greater (P < 0.05) than OM digestibility determined by IVOMD and IADF for all
      forages except bahiagrass, for which IADF did not differ from TFC. In Year 1, OM
      intake (OMI) of 10-wk limpograss was less (P < 0.05) than all other 4-wk forages.
      In Year 2, voluntary OMI of 10-wk limpograss was less (P < 0.05) than all grass x
      maturity combinations, except for 10-wk bermudagrass. These data suggest that
      important differences exist in changes in nutrient quality associated with
      increased maturity in tropical forages. Among the forages assessed in this study,
      bahiagrass seems to better retain nutrient quality when maturing from 4 to 10 wk.

PMID- 15956483
TI  - Ocular manifestations of cat-scratch disease: role of MR imaging.

PMID- 15956484
TI  - Is current imaging good enough to differentiate radiation-induced brain injury
      from tumor recurrence?

PMID- 15956485
TI  - USPIOs to enhance the diagnostic potential of ultrasound in tumor and other
      inflammatory lesions.

PMID- 15956487
TI  - When is the abnormal normal?

PMID- 15956486
TI  - Ischemia and multiple sclerosis: perfusion MR imaging provides insight into an
      underexplored pathophysiology.

PMID- 15956488
TI  - Optic neuropathy secondary to cat scratch disease: distinguishing MR imaging
      features from other types of optic neuropathies.
AB  - BACKGROUND AND PURPOSE: MR imaging characteristics of optic neuropathy caused by
      cat scratch disease have not yet been described; this lack of information may
      result in incorrect diagnosis and may contribute to initiation of inappropriate
      therapy. Our study was based on the hypothesis that cat scratch disease-related
      optic neuropathy has distinct MR imaging features compared with those of other
      types of optic neuropathies. METHODS: Eighty-two patients with various causes of
      optic neuropathy and available MR imaging examinations were included in this
      study. Two readers blinded to the diagnosis reviewed the MR images independently
      in regard to presence, location, and extent of optic nerve enhancement. The MR
      imaging findings were correlated with the final diagnosis. RESULTS: Eleven
      percent (9/82) of the patients received a final diagnosis of cat scratch disease.
      Optic nerve enhancement in patients with cat scratch disease (5/37) was localized
      to a 3- to 4-mm segment at the optic nerve-globe junction. All other patients
      with optic neuropathy (31/37) with one exception showed enhancement away from the
      optic nerve-globe junction or a long-segment enhancement when the optic nerve
      globe junction was also involved. Four patients with cat scratch disease did not
      show any optic nerve MR abnormalities. CONCLUSION: Unilateral, short-segment
      enhancement localized to the optic nerve-globe junction is highly specific for
      cat scratch disease as the underlying cause of optic neuropathy and may help in
      establishing the diagnosis of this condition.

PMID- 15956489
TI  - Foramen tympanicum, or foramen of Huschke: pathologic cases and anatomic CT
      study.
AB  - BACKGROUND AND PURPOSE: A persistent foramen tympanicum, or foramen of Huschke,
      is an anatomic variation of the tympanic portion of the temporal bone due to a
      defect in normal ossification in the first 5 years of life. The foramen is
      located at the anteroinferior aspect of the external auditory canal (EAC),
      posteromedial to the temporomandibular joint (TMJ). We sought to define its
      prevalence, location, and size on high-resolution spiral CT (HRCT). METHODS: We
      prospectively examined 102 consecutive HRCT studies of the temporal bone (204
      ears). HRCT was performed by using 120 kV, 400 mAs, an ultra-high-resolution
      filter, 0.6-mm section thickness, 0.3-mm section increment, 728 x 728 matrix, and
      160-mm field of view. We noted the size and location of the foramen tympanicum
      relative to the tympanic membrane and calculated its prevalence. Patients with
      focally decreased tympanic bone thickness of <1 mm at the anteroinferior EAC
      (between the 3- and 6-o'clock positions) were considered separately. RESULTS: We
      found a foramen tympanicum was found in six (4.6%) of 130 ears. Mean axial
      diameter was 4.2 mm, and mean sagittal diameter was 3.6 mm. Focally reduced bone
      thickness in the same location was found in 45 (35%) ears, with a female
      preponderance (P = .003). CONCLUSION: HRCT is sensitive for detection of the
      foramen tympanicum because of its thin sections, high spatial resolution, and
      multiplanar capabilities. Awareness of this anatomic entity may be useful in
      evaluating patients with transient otorrhea in whom no otologic cause (e.g., ear
      infection, TMJ disease) is identified.

PMID- 15956490
TI  - Otologic manifestations of petrous carotid aneurysms.
AB  - BACKGROUND AND PURPOSE: The petrous and cavernous segments of the extradural
      internal carotid artery take a complex course through the skull base before
      entering the subarachnoid space distal to the cavernous sinus. Despite the
      protection from trauma afforded by the anatomy, the petrous and carotid internal
      carotid artery (ICA) segments of the vessel remains subject to disease, the most
      important of which are aneurysms. Aneurysms affecting the petrous portion of the
      vessel are extremely uncommon, and presentation with otologic symptoms is
      unusual. These symptoms include hearing loss, tinnitus, and life threatening
      hemorrhage. This article emphasizes the need for a high level of suspicion for
      aneurysm as a potential cause for otologic symptoms. We report and discuss three
      cases of petrous carotid aneurysms with otologic manifestations to increase the
      awareness and aid in the diagnosis and treatment of this uncommon disorder.
      METHODS: The medical records and imaging studies of three patients presenting to
      our institution with aneurysms involving the petrous internal carotid artery were
      reviewed. One presented with progressive bilateral sensorineural hearing loss.
      The next patient presented with pulsatile tinnitus. The last patient presented to
      the emergency room unresponsive with severe epistaxis. RESULTS: All three
      patients had imaging studies revealing petrous carotid aneurysms. Each patient
      had symptoms related to the aneurysms ranging from hearing loss, tinnitus, and
      life-threatening hemorrhage. CONCLUSION: Petrous carotid aneurysms are rare, and
      presentation with otologic symptoms is unusual. Awareness of these lesions as a
      cause of otologic symptoms, however, is highly important. These cases also
      illustrate the usefulness of endovascular treatments for aneurysms of the petrous
      portion of the internal carotid artery, which are extremely difficult to treat by
      using an open surgical approach.

PMID- 15956491
TI  - Intraparotid facial nerve schwannoma: a report of five cases and an analysis of
      MR imaging results.
AB  - We present five cases of intraparotid facial nerve schwannoma. In four of the
      five cases, tumors arising from the main facial nerve trunk were centered just
      below the skull base near the stylomastoid foramen and had a small cranial
      extension into the lower facial nerve canal. In three cases, each tumor had
      higher signal intensity around the periphery on T2-weighted images (target sign).
      These findings may be highly suggestive of an intraparotid facial nerve
      schwannoma.

PMID- 15956492
TI  - Alveolar soft-part sarcoma of the head and neck: clinical and imaging features in
      five cases.
AB  - BACKGROUND AND PURPOSE: Alveolar soft-part sarcoma (ASPS) of the head and neck is
      an extremely rare malignancy. Although the clinical and imaging features of this
      tumor have been reported, a periodic review of unusual tumors is useful. The
      purpose of this study was to describe the clinical and imaging features of ASPS
      of the head and neck. METHODS: Between January 1990 and May 2004 at our
      institution, five head and neck ASPS were diagnosed in five patients (two male
      and three female patients; age range, 4-22 years). Clinical and imaging findings
      were reviewed retrospectively. Imaging studies consisted of contrast material
      enhanced CT (in four patients), MR imaging (in four patients), and digital
      subtraction angiography (in two patients). RESULTS: The locations of the tumor
      were tongue in two cases, larynx in one case, buccal space in one case, and
      paravertebral space in one case. This tumor appeared as a large lobulating
      contoured mass with high signal intensity and flow voids on T2-weighted images
      and showed strong enhancement on contrast-enhanced CT and MR images. Preoperative
      angiography showed high vascularity. Wide surgical excisions were performed in
      four cases. Mean follow-up periods were 16 months (range, 6-30 months), and no
      recurrence was noted except for the laryngeal case. CONCLUSION: ASPS should be
      included in the differential diagnosis of head and neck tumor when a slow
      growing, large mass with high signal intensity and flow voids on T2-weighted
      images and strong enhancement on contrast-enhanced CT or MR image is seen,
      particularly in young female patients.

PMID- 15956493
TI  - Cellular leiomyoma of the nasal cavity: findings of CT and MR imaging.
AB  - Nasal leiomyoma, a benign tumor composed of smooth muscle cells, is rare in the
      head and neck region. Cellular leiomyomas of the uterus exhibit high intensity on
      T2-weighted images. Here we present a case of nasal leiomyoma in which the
      pathologic findings are similar to those of cellular leiomyoma. The present case
      exhibited slightly elevated intensity on T2-weighted images and marked
      enhancement on postcontrast images. CT findings showed a soft tissue lesion
      without bone erosion. These findings appear to be characteristic of intranasal
      leiomyoma.

PMID- 15956494
TI  - Bilateral dystrophic ossification of the thyroid cartilage appearing as
      symmetrical laryngeal masses.
AB  - Primary cartilaginous lesions of the larynx are relatively uncommon. We present a
      case of bilaterally pseudocystic lesion of the thyroid cartilage that
      demonstrated progressive calcification. Pathologic analysis showed features
      suggesting a dystrophic lesion with no evidence of malignancy. We hypothesize
      that repetitive microtrauma related to muscular overuse probably led to
      inflammatory changes at tendinous insertions on the laryngeal cartilage and
      resulted in dystrophic ossification of the laryngeal cartilage.

PMID- 15956495
TI  - Three-dimensional packing with complex orbit coils for the endovascular treatment
      of intracranial aneurysms.
AB  - BACKGROUND AND PURPOSE: Endovascular treatment of intracranial aneurysms is too
      often associated with aneurysm recurrence due to coil compaction. High packing of
      coils prevents compaction. To increase the packing attenuation, we sought to
      evaluate the results of selective embolization of aneurysms with complex-shaped
      coils alone. METHODS: Twenty consecutive patients with an intracranial aneurysm
      were treated by selective embolization. There were 12 women and eight men, with a
      mean age of 48 years. Fourteen patients presented with subarachnoid hemorrhage,
      whereas six were asymptomatic. Mean size of aneurysms was 5 mm (range, 3-11 mm).
      In all cases, we tried to pack the aneurysm with complex coils only (Orbit,
      Cordis, Miami Lakes, FL), delivered in a concentric fashion. Remodeling technique
      was used in two cases of wide-neck aneurysms. Clinical and anatomic outcome were
      assessed by using the modified Glasgow outcome scale and 6-month MR angiography
      (MRA). RESULTS: From two to five complex coils were delivered within the
      aneurysms. Occlusion by using complex coils alone was successful in 16 patients,
      and resulted in 14 complete occlusions and two neck remnants. In four patients,
      additional helical Orbit coils or Guglielmi detachable coils were required to
      complete aneurysm obliteration. No technical complication occurred, and clinical
      outcome was excellent in 14 cases and good in two. Follow-up MRAs were obtained
      in all patients and showed only one slight recanalization. CONCLUSIONS:
      Intracranial aneurysms may be treated by selective embolization with complex
      coils only. Imaging follow-up at 6 months shows a low rate of coil compaction.

PMID- 15956496
TI  - MR angiography at 3T versus digital subtraction angiography in the follow-up of
      intracranial aneurysms treated with detachable coils.
AB  - BACKGROUND AND PURPOSE: Digital subtraction angiography (DSA) is used to follow
      up intracranial aneurysms treated with detachable coils to identify recurrence
      and determine need for additional treatment. However, DSA is invasive and
      involves a small risk of neurologic complications. We assessed the feasibility
      and usefulness of 3D time-of-flight (TOF) MR angiography (MRA) performed at 3T
      compared with DSA for the follow-up of coil-treated intracranial aneurysms.
      METHODS: In a prospective study, 20 consecutive patients with 21 intracranial
      aneurysms treated with coils underwent DSA and nonenhanced and enhanced multiple
      overlapping thin-slab acquisition 3D TOF MRA at 3T on the same day at a mean
      follow-up of 6 months (range, 4-14 months) after coil placement. MRA images were
      evaluated for presence of artifacts, presence and size of aneurysm remnants and
      recurrences, patency of parent and branch vessels, and added value of contrast
      material enhancement. MRA and DSA findings were compared. RESULTS: Interobserver
      agreement of MRA was good, as was agreement between MRA and DSA. All three
      recurrences that needed additional treatment were detected with MRA. Minor
      disagreement occurred in four cases: three coil-treated aneurysms were scored on
      MRA images as having a small remnant, whereas on DSA images these aneurysms were
      occluded; the other aneurysm was scored on MRA images as having a small remnant,
      whereas on DSA images this was a small recurrence. Use of contrast material had
      no additional value. Coil-related MR imaging artifacts were minimal and did not
      interfere with evaluation of the occlusion status of the aneurysm. CONCLUSION:
      High-spatial-resolution 3D TOF MRA at 3T is feasible and useful in the follow-up
      of patients with intracranial aneurysms treated with coil placement.

PMID- 15956498
TI  - Preventing spontaneous thrombosis of experimental sidewall aneurysms: the oblique
      cut.
AB  - In our experience with the canine model, sidewall aneurysms made with an oblique
      cut arteriotomy were less likely to thrombose than were those made with a
      standard technique.

PMID- 15956497
TI  - Selective intraarterial nimodipine treatment in an experimental subarachnoid
      hemorrhage model.
AB  - BACKGROUND AND PURPOSE: Cerebral vasospasm secondary to subarachnoid hemorrhage
      (SAH) has been a serious clinical problem. The aim of the present study is to
      evaluate the efficacy of selective intraarterial (IA) nimodipine treatment in a
      rabbit model of chronic cerebral vasospasm. METHODS: Twenty-two adult New-Zealand
      rabbits of either sex, weighing 2500-3800 g were used for this study. Following a
      control angiography, all animals received 1 mL of fresh unheparinized autologuous
      arterial blood into the cisterna magna. Three days later, the presence of
      vasospasm was demonstrated angiographically by selective vertebral artery
      injection. The experimental design was as follows: separate groups of animals (n
      = 5, in each group) received nimodipine (0.05 mg/kg), papaverine (6 mg/kg), or
      vehicle intraarterially, after placement of a microcatheter into the vertebral
      artery. Another group (n = 5) received nimodipine (0.05 mg/kg) directly into the
      cisterna magna, and vehicle injection was made into cisterna magna in two other
      animals. Thirty minutes after treatment, angiographies were repeated and changes
      in arterial diameter were expressed as percentages of control. RESULTS: IA
      nimodipine and IA papaverine were effective in relieving veretebral and basilary
      vasospasm (P < .05). IA nimodipine was more effective than IA papaverine (P <
      .05). IA nimodipine was not more effective than intrathecal (IT) nimodipine in
      relieving vertebral artery vasospasm, although it was more effective than IT
      nimodipine in basilar artery. Vehicle injections (IA or IT) failed to reverse the
      vasospasm induced by autologuous blood injection. CONCLUSION: This study showed
      that selective IA nimodipine treatment may be considered as an alternative in the
      treatment of chronic vasospasm following SAH.

PMID- 15956499
TI  - CT angiography with electrocardiographically gated reconstruction for visualizing
      pulsation of intracranial aneurysms: identification of aneurysmal protuberance
      presumably associated with wall thinning.
AB  - Electrocardiographically (ECG) gated multisection helical CT images were obtained
      in 23 patients with ruptured intracranial aneurysms. 4D-CTA (3D CT angiography
      plus phase data) images were generated by ECG-gated reconstruction. Four patients
      showed pulsation of an aneurysmal bleb. Clipping was performed in two of these
      patients, and the rupture site matched the pulsatile bleb seen in 4D-CTA.

PMID- 15956500
TI  - Extravasation from rupturing aneurysm demonstrated by 3D digital subtraction
      angiography.
AB  - We describe the 3D digital subtraction angiography (3D-DSA) image of
      extravasation from a rupturing aneurysm. This image clearly showed that the
      extravasation was coming from a pseudoaneurysm on an aneurysmal wall. To the best
      of our knowledge, this is the first demonstration of a 3D-DSA image of a
      rupturing aneurysm.

PMID- 15956501
TI  - Carotid ophthalmic aneurysm rupture after parent vessel occlusion.
AB  - We report causes leading to and rupture of a carotid ophthalmic aneurysm after
      treatment by parent vessel occlusion. The aneurysm was initially symptomatic but
      unruptured.

PMID- 15956502
TI  - Techniques for intracranial stent navigation in patients with tortuous vessels.
AB  - BACKGROUND AND PURPOSE: In some patients with stenosis of an intracranial artery,
      navigating the balloon or stent-delivery system is difficult of tortuous anatomy
      of the aortic arch, carotid arteries, or vertebral arteries Our purpose was to
      describe techniques of intracranial stent placement that help in navigating the
      stent-delivery system in tortuous vessels. METHODS: Between May 1998 and June
      2004, 73 symptomatic stenotic (>50%) intracranial arteries were successfully
      treated with stent-assisted angioplasty. In 11 cases, standard techniques of
      navigating the stent-delivery system into the intended lesion failed because of
      vascular tortuosity. In these difficult cases, several techniques were used to
      overcome the tortuosity. Five lesions were located in the middle cerebral
      arteries, four were in the supraclinoid internal carotid arteries, and two were
      in the distal vertebral arteries. RESULTS: In all difficult cases, stents were
      successfully placed in the intracranial artery by using several techniques: 1)
      waiting method in which we waited for 20-30 minutes after advancement of the
      microwire across the lesion, 2) the double-wire technique, and 3) the coaxial
      double-guiding catheter technique. The waiting method made smooth stent
      navigation possible in five cases, the double-wire technique was successful in
      four cases, and the coaxial double-guiding catheter technique was effective in
      two cases. No technique-related complications occurred. CONCLUSION: In difficult
      cases in which standard techniques of navigating the stent-delivery system into
      the intended lesion fail because of vascular tortuosity, our techniques were
      useful methods for intracranial stent navigation.

PMID- 15956503
TI  - Stent-assisted angioplasty of symptomatic intracranial vertebrobasilar artery
      stenosis: feasibility and follow-up results.
AB  - BACKGROUND AND PURPOSE: The natural history of symptomatic, untreated posterior
      circulation stenosis is dismal, with many patients experiencing significant
      morbidity or mortality. The purpose of this study was to evaluate the feasibility
      and results of stent-assisted angioplasty of symptomatic intracranial
      vertebrobasilar artery stenosis. METHODS: We reviewed the imaging findings and
      medical records of 17 consecutive patients who were treated with stent-assisted
      angioplasty for medically refractory vertebrobasilar artery stenosis. The
      location of the lesion, degree of stenosis, procedure-related complications, and
      clinical and short- and long-term angiographic results were assessed. RESULTS:
      The population included 17 cases (10 men, seven women; age range, 51-74 years;
      mean, 64 years). The locations of the lesions were intracranial vertebral artery
      (n = 13) and basilar artery (n = 6). The mean degree of stenosis decreased from
      76.1 +/- 14.6% before stent-assisted angioplasty to 1.3 +/- 2.8% (P < .05) after
      the procedure. Acute in-stent thrombosis developed in one case (6%, Mori type B
      lesion), which was successfully treated with intraarterial abciximab infusion and
      angioplasty. Another patient (6%, Mori type C lesion) developed immediate
      postprocedural transient diplopia and ataxia, which gradually resolved. No other
      patient showed symptoms related to the vertebrobasilar artery lesion at follow
      up. No significant restenosis was observed at short-term (five patients; follow
      up range, 0.5-6 months; mean, 4.3 months) or long-term (six patients; follow-up
      range, 12-41 months; mean, 21 months) angiographic follow-up. CONCLUSION: Stent
      assisted angioplasty is a feasible treatment method for vertebrobasilar artery
      stenosis. The patency of the stent-assisted angioplasty seems to be preserved in
      the long-term, with good clinical outcome.

PMID- 15956504
TI  - Treatment of vertebrobasilar occlusion by using a coronary waterjet thrombectomy
      device: a pilot study.
AB  - BACKGROUND AND PURPOSE: Despite improved patient outcomes because of
      intraarterial fibrinolysis, vertebrobasilar thromboembolism remains a fatal
      disease with a death rate of more than 50%. The outcome depends on the success of
      recanalization. Fibrinolysis achieves recanalization in only 50%-70% of the
      cases. Therefore, we investigated the feasibility of using a coronary mechanical
      device to increase the recanalization rate. METHODS: Twelve patients with acute
      vertebrobasilar occlusion were included in the pilot study. The older 5F and the
      new 4F versions of the Possis Angiojet catheter, which use a waterjet to attract,
      fragment, and extract the thrombus, were used. Inclusion depended on the presence
      of acute multisegmental intracranial or any extracranial vertebrobasilar
      occlusion. Exclusion criteria included coma lasting >8 hours and age >80. The
      Angiojet treatment did not exclude other therapeutic options. RESULTS: The
      Angiojet catheter accessed the thrombosed site in 10 of 12 patients. Combined
      treatment with the Angiojet and additional fibrinolysis or angioplasty resulted
      in a recanalization rate of 100%. Of 37 occluded vertebrobasilar segments, 30
      were primarily recanalized with the Angiojet. Three symptomatic and two
      asymptomatic hemorrhages were detected by CT. Five of the 12 patients died. Fifty
      percent of all patients obtained a moderate to excellent outcome (Modified Rankin
      Scale 0-3). CONCLUSIONS: Use of the coronary Angiojet in the vertebrobasilar
      system is feasible. The device has the potential to increase the recanalization
      rate, especially in cases of extensive thrombosis, and, thus, improve patient
      outcomes.

PMID- 15956505
TI  - Successful thrombectomy in acute terminal internal carotid occlusion using a
      basket type microsnare in conjunction with temporary proximal occlusion: a case
      report.
AB  - Recanalization therapy is controversial in patients with acute stroke due to
      terminal internal carotid artery (ICA) occlusion. A 78-year-old man underwent
      successful percutaneous transarterial microsnare-assisted thrombectomy (PMT) for
      the treatment of acute terminal ICA occlusion, which was recanalized completely.
      This case report suggests that PMT is a potential treatment for patients with
      acute embolic occlusion of the terminal ICA.

PMID- 15956506
TI  - Endovascular treatment of high-flow carotid cavernous fistulas by stent-assisted
      coil placement.
AB  - BACKGROUND AND PURPOSE: Endovascular techniques are the methods of choice for the
      treatment of patients with carotid cavernous fistulas. We report our experience
      using stent-assisted coil placement for treatment of patients with high-flow
      fistulas that are associated with severe laceration of the internal carotid
      artery. METHODS: In a retrospective review of an internal endovascular therapy
      database covering the interval between October 2001 and October 2003, we
      identified a total of 5 patients presenting with 6 high-flow type A carotid
      cavernous fistulas (one had a bilateral fistula) that were associated with severe
      laceration of the internal carotid artery. All were treated first with stenting
      of the injured segment of the internal carotid artery followed by transarterial
      (3/6) and/or transvenous (4/6) obliteration of the fistula with detachable
      platinum coils. In 2 cases, a liquid adhesive was also used. In all instances, a
      compliant balloon was inflated within the stented arterial segment during coil
      deposition to avoid extension of coils into the parent artery. RESULTS: All 6
      fistulas were obliterated, and each internal carotid artery was successfully
      reconstructed. Except for posttraumatic cranial nerve dysfunction in 1 patient,
      clinical outcome was very good. Follow-up angiograms in 3 of the 6 patients
      obtained at intervals between 3 and 6 months (mean, 4.5 months) revealed no
      fistula recurrence and no evidence of intimal hyperplasia within the stent.
      CONCLUSION: In this series of patients with high-flow carotid cavernous fistula
      associated with severe injury to the internal carotid artery, stent-assisted coil
      placement offered a safe and effective treatment. Stent-assisted coil placement
      may increase the ability to successfully treat fistulas with severe injury to the
      internal carotid artery with preservation of the parent artery.

PMID- 15956507
TI  - Feasibility of using hyperosmolar mannitol as a liquid tumor embolization agent.
AB  - BACKGROUND AND PURPOSE: This study assesses the cytotoxicity of hyperosmolar
      mannitol on human endothelial and meningioma cells in vitro and summarizes the
      initial clinical experience of using mannitol as a liquid tumor embolization
      agent. METHODS: Human umbilical vein endothelial cells and primary meningioma
      cells from surgical specimens were treated with 300, 600, 900, and 1200 mOsm of
      mannitol, mannitol and iohexol mixture, saline, and iohexol alone. Cell death was
      evaluated with a Live/Dead kit and quantified with thymidine incorporation. From
      1998 to 2004, 23 patients with meningioma were treated with mannitol and 31
      patients were treated with polyvinyl alcohol (PVA) particles alone. Angiographic
      results, procedural complications, intraoperative observation, and estimated
      blood loss during surgical resection were retrospectively evaluated. RESULTS:
      Minimal endothelial cell death was seen after incubation with 300 mOsm of
      mannitol for 15 minutes, but 43 +/- 2% of endothelial cells were damaged by 1200
      mOsm of mannitol after 30 minutes. Five meningioma cell lines exhibited
      significant cell death (22 +/- 2%; P < .05) after incubation with mannitol.
      Satisfactory angiographic results were obtained in all 23 patients. Tumor
      necrosis was observed intraoperatively and confirmed pathologically. There was no
      significant difference in estimated blood loss between mannitol- and PVA
      embolized patients (407 +/- 64 mL vs 381 +/- 50 mL; P > .75). CONCLUSION: High
      concentration of mannitol can injure endothelial cells and meningioma cells in a
      short period of time. It is feasible to use mannitol as a liquid embolic agent to
      treat meningioma.

PMID- 15956508
TI  - Neurologic complications after particle embolization of intracranial meningiomas.
AB  - BACKGROUND AND PURPOSE: Preoperative embolization of meningiomas is frequently
      used to facilitate surgery and to reduce intraoperative blood loss. The purpose
      of this study was to evaluate the frequency of procedure-related neurologic
      complications during and after particle embolization of intracranial meningiomas.
      METHODS: Between 1996 and 2004, 185 consecutive patients underwent particle
      embolization of an intracranial meningioma. Devascularization was performed by
      means of superselective probing of the tumor-feeding vessels and ensuing free
      flow embolization with spherical particles. All procedures were performed with
      systemic heparinization. RESULTS: Six patients (3.2%) had ischemic events with
      neurologic deficit. Two had amaurosis, and four patients presented with
      hemiparesis. Hemorrhage occurred in six patients (3.2%). In five of these
      patients, rapid microsurgical tumor removal resulted in a favorable outcome
      without persistent neurologic deficit. In one patient, massive intratumoral,
      subarachnoid, and subdural hemorrhage was lethal. CONCLUSION: Particle
      embolization of meningiomas is associated with a substantial risk of ischemic and
      hemorrhagic events. The individual risk-to-benefit ratio of embolization should
      be thoroughly considered.

PMID- 15956509
TI  - Efficacy and safety of the perclose closer s device after neurointerventional
      procedures: prospective study and literature review.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the efficacy and
      safety of the 6F Closer S device (Perclose; Redwood City, CA) versus manual
      compression to close arteriotomy sites after neurointerventional procedures in
      both virgin vessels and those previously treated with the device. METHODS: This
      single-center, multiple-operator, controlled, prospective study included 475
      procedures (337 patients) with the device and 79 procedures (79 patients) with
      manual compression. A substantial number of patients receiving anticoagulation
      and/or antiplatelet medications were included. Efficacy and safety were evaluated
      on the basis of the rate of hemostatic success and the incidence of clinically
      significant complications. The literature was reviewed by using MEDLINE. RESULTS:
      Overall success rates were 95% in the device group versus 96% in the manual
      compression group (P = 0.78), and clinically relevant complication rates were
      0.6% versus 2.5%, respectively (P = 0.15). Success rates significantly declined
      in vessels previously treated with the device three or more times. However,
      complication rates did not significantly change. Literature review yielded 12
      articles reporting complication rates of 3.2-35% for the device and 2.3%-33.3%
      for manual compression. CONCLUSION: The device was safe and effective for closing
      arteriotomy sites in patients undergoing neurointerventional procedures,
      including those receiving anticoagulation/antiplatelet therapy or those
      previously treated with the device one or two times.

PMID- 15956510
TI  - From patient to model: stereolithographic modeling of the cerebral vasculature
      based on rotational angiography.
AB  - We developed a method to produce tubular in vitro models of the cerebral vessels
      from real patient data. Three-dimensional data sets obtained from patients
      undergoing rotational angiography were used for stereolithographic biomodeling by
      using rapid prototyping technology. In a second step, tubular reproductions of
      the cerebral vessels were obtained by using the lost-wax technique. These
      reproductions can be useful for hemodynamic research and for the development and
      preclinical evaluation of new endovascular treatment methods.

PMID- 15956511
TI  - Stereolithographic vascular replicas from CT scans: choosing treatment
      strategies, teaching, and research from live patient scan data.
AB  - Our goal was to develop a system that would allow us to recreate live patient
      arterial pathology by using an industrial technique known as stereolithography
      (or rapid prototyping). In industry, drawings rendered into dicom files can be
      exported to a computer programmed to drive various industrial tools. Those tools
      then make a 3D structure shown by the original drawings. We manipulated CT scan
      dicom files to drive a stereolithography machine and were able to make replicas
      of the vascular diseases of three patients.

PMID- 15956512
TI  - Phase-sensitive T1 inversion recovery imaging: a time-efficient interleaved
      technique for improved tissue contrast in neuroimaging.
AB  - BACKGROUND AND PURPOSE: High tissue contrast and short acquisition time are
      desirable when scanning patients. The purpose of this report is to describe the
      implementation of a new technique for generating high gray matter (GM) and white
      matter (WM) contrast in a short scan time, make a quantitative evaluation of the
      contrast efficiency, and explore its potential applications in neuroimaging.
      METHOD: A fully interleaved T1-weighted inversion recovery (T1IR) sequence with
      phase-sensitive reconstruction (PS-T1IR) is implemented. This sequence is
      compared with conventional T1-weighted spin-echo imaging (T1SE) and T1-weighted
      fluid-attenuated inversion recovery (T1FLAIR). The time efficiency and contrast
      enhancement have been quantitatively analyzed in normal volunteers. The
      performance of the sequence is evaluated in >30 patients with neurologic
      disorders. The sensitivity of PS-T1IR relative to T1SE in detecting gadolinium
      enhancements is also evaluated. RESULTS: PS-T1IR is more time-efficient than T1SE
      and generates better GM-WM contrast. It results in the best contrast-to-noise
      ratio (CNR) efficiency (1.16) compared with T1FLAIR (0.73) and T1SE (0.23). For a
      typical clinical protocol, PS-T1IR takes only 1:30 minutes versus 2:40 minutes
      for T1SE imaging for the whole brain coverage. Although gadolinium enhancements
      are detected with comparable sensitivity on both PS-T1IR and T1SE sequences, in
      certain instances, the latter sequence appears to be more sensitive in
      demonstrating gadolinium enhancements within WM. CONCLUSION: PS-T1IR has the
      highest CNR efficiency compared with T1FLAIR and T1SE. It is a very practical
      technique for neuroradiologic applications.

PMID- 15956513
TI  - Reference values for long echo time MR spectroscopy in healthy adults.
AB  - BACKGROUND AND PURPOSE: There is a lack of information with regard to normal
      metabolic ratios acquired with MR spectroscopy utilizing a long echo time
      technique. Our purpose was to measure metabolic ratios in healthy adults to
      determine whether the metabolites varied across brain regions and by sex.
      METHODS: Single voxel proton spectra were acquired with an echo time of 135
      milliseconds in 10 brain regions of 72 healthy subjects ranging in age from 20 to
      44 years. Six gray matter sites in the cerebrum included four cortical areas in
      the frontal, parietal, temporal, and occipital lobes, and two deep nuclear sites
      in the basal ganglia and the thalamus. Two subcortical white matter regions were
      in the parietal and the frontal lobes. Two posterior fossa sites included the
      pons and the cerebellum. All 10 brain regions were not studied in each subject.
      For each spectrum, the metabolites n-acetylaspartate (NAA), creatine (Cr), and
      choline (Ch) were identified and ratios of NAA/Cr and Ch/Cr calculated for each
      brain region. A multifactorial analysis of variance was performed with the two
      metabolic ratios as dependent variables and with brain region and sex as
      independent variables. Post hoc statistical analysis consisted of the Scheffe F
      statistic for significant difference between pairs of brain regions for both
      metabolic ratios. RESULTS: There was significant regional variation for both the
      NAA/Cr ratio (P < .0001) and the Ch/Cr ratio (P < .0001). The NAA/Cr ratio was
      consistent within cortical gray and white matter but differed between cortical
      gray (smaller ratio) and white matter (larger ratio). The Ch/Cr ratio was
      variable in the gray matter, differed between some but not all gray and white
      matter regions, but was consistent within subcortical white matter regions. There
      was no difference between men and women for either metabolic ratio. CONCLUSION:
      There was variation of the NAA/Cr ratio and the Ch/Cr ratio across brain regions,
      but no sex differences were found. These findings provide the requisite normative
      values to use single voxel, long-echo-time MR spectroscopy in adult patients with
      neurologic disorders.

PMID- 15956514
TI  - Dynamic susceptibility-weighted perfusion imaging of high-grade gliomas:
      characterization of spatial heterogeneity.
AB  - BACKGROUND AND PURPOSE: The advent of new anti-angiogenic therapies has created
      the need for better defining regions of abnormal vascularity in order to add
      specificity to the classification of high-grade gliomas. This study investigated
      MR imaging parameters corresponding to the peak height and percent recovery of
      the T2* relaxivity curve to characterize angiogenesis and microvascular leakage
      within the T2 and contrast-enhancing abnormalities in high-grade gliomas.
      METHODS: Dynamic susceptibility-weighted MR imaging was performed in 41 patients
      with untreated high-grade glioma during the first pass and recirculation phase of
      a gadolinium bolus injection. Normalized peak height and percent recovery of the
      post-bolus signal were calculated on a voxel by voxel basis within the T2 and
      contrast-enhancing lesions (T2L, CEL) and compared between grade III and grade IV
      gliomas. RESULTS: Grade IV gliomas showed significantly larger volumes of
      abnormal peak height and recovery compared to grade III patients (P < .01).
      Within the CEL, grade IV gliomas exhibited significantly higher peak height
      values than grade III patients (P < .05). Enhancing grade III patients (n = 7)
      demonstrated higher minimum values of percent recovery within both regions
      compared to grade IV patients. Non-enhancing grade III gliomas (n = 11) had
      significantly elevated minimum percent recovery values when compared to the T2L
      CEL region in grade IV patients (n = 23; P < .05). CONCLUSION: Direct measurement
      of the spatial distribution of tumor microvasculature characteristics has shown
      considerable heterogeneity within different regions of grade III and grade IV
      gliomas. Peak height and percent recovery parameters help to improve the
      specificity for characterization of the degree of angiogenesis and microvascular
      leakage in these tumors and may be useful in evaluating response to treatment.

PMID- 15956515
TI  - Diffusion-weighted imaging of radiation-induced brain injury for differentiation
      from tumor recurrence.
AB  - BACKGROUND AND PURPOSE: Differentiation between tumor recurrence and treatment
      related brain injury is often difficult with conventional MRI. We hypothesized
      that the diffusion-weighted imaging (DWI) could help differentiate these 2
      conditions, because water diffusion may be greater for necrotic tissues in the
      treatment-related brain injury than for tumor tissues in recurrence. Our aim was
      to analyze whether DWI findings of recurrent tumor are distinct from those of
      radiation necrosis. METHODS: Seventeen patients were examined prospectively. Two
      readers assessed the images by consensus for homogeneity and signal intensity of
      the lesions. Five regions of interest were drawn within the lesions on trace DWI
      images and apparent diffusion coefficient (ADC) maps. The minimal, maximal, and
      mean values of each lesion were compared between the 2 groups. Findings in 12 of
      17 patients were verified histologically by surgery or biopsy; the diagnoses in
      the remaining 5 patients were made on the basis of follow-up MRI findings and
      clinical follow-up. RESULTS: There were a total of 20 lesions; 12 lesions were
      due to radiation necrosis and 8 lesions to tumor recurrence. In the radiation
      necrosis group, 8 lesions had marked hypointensity. In the recurrence group,
      however, no marked hypointensity was seen. The maximal ADC values within each
      lesion were significantly smaller for the recurrence group than for the necrosis
      group (P = .039). CONCLUSION: Radiation necrosis usually showed heterogeneity on
      DWI images and often included spotty, marked hypointensity. Significant
      difference was found in the maximal ADC values between radiation necrosis and
      tumor recurrence. DWI was useful in differentiating recurrent neoplasm from
      radiation necrosis.

PMID- 15956516
TI  - Mapping the functional anatomy of sentence comprehension and application to
      presurgical evaluation of patients with brain tumor.
AB  - BACKGROUND AND PURPOSE: The main clinical indication for functional MR imaging
      (fMRI) has been to preoperatively map the cortex. Motor paradigms to activate the
      cortex are simple and robust; however, language tasks show greater variability
      and difficulty. The aim of this study was to develop a language task with an
      adequate control task to engage the areas of the posterior temporal lobe
      responsible for sentence comprehension. METHODS: We performed a cloze paradigm
      requiring silent reading of a visually presented sentence-completion task based
      on semantic meaning versus a letter-scanning epoch requiring the completion of
      nonlinguistic strings or a rest period. Before this task was clinically used in
      two patients epilepsy and cavernous angioma, its feasibility and accuracy were
      tested in 14 healthy right-handed participants. RESULTS: Results showed
      significant activation of the posterior temporal cortex, including a broad area
      across the posterior left temporal cortex extending into the inferior parietal
      lobule. When the sentence completion-minus-letter string task was compared with
      the sentence completion-minus-rest task, increased activation was present in the
      posterior temporal lobe. CONCLUSION: Decreased significant activation during the
      sentence completion-minus-rest contrast may be attributed to increased noise from
      intersubject variability in the rest period. Our results suggest that this task
      elucidates areas important to reading comprehension in the posterior and inferior
      temporal regions that verbal fluency and auditory discrimination tasks do not.
      Data from two cases are summarized to exemplify the input of this task for
      neurosurgery.

PMID- 15956517
TI  - Iron particles enhance visualization of experimental gliomas with high-resolution
      sonography.
AB  - BACKGROUND AND PURPOSE: Intraoperative MR imaging and sonography are used for
      navigation during neurosurgical procedures. The purpose of this experimental
      study was to evaluate the potential of high-resolution sonography using
      superparamagnetic iron oxide (SPIO) particles as a contrast medium to delineate
      brain tumors and to relate these findings with those of MR imaging. METHODS: C6
      gliomas were implanted in 36 rats. Eleven days after tumor implantation, the
      animals underwent MR imaging with a 1.5-T MR imaging unit. Twelve animals
      received gadopentetate dimeglumine immediately before the MR examination, 12
      animals were injected with SPIO particles 24 hours before MR imaging, and 12
      animals received no contrast agent. Immediately after MR imaging, the animals
      were sacrificed and their brains were removed and placed in saline. Sonography
      was performed instantly after brain removal. Brains were embedded in paraffin,
      and sections were stained for iron with Perl's stain and for macrophages with ED
      1 immunohistochemistry. RESULTS: At MR imaging, the tumors appeared hyperintense
      on T2-weighted and gadolinium-enhanced T1-weighted images. After application of
      SPIO particles, they became markedly hypointense on T2-weighted images and hypo-
      to hyperintense on T1-weighted images. On sonograms, gliomas were iso- to
      slightly hyperechoic to normal brain parenchyma on nonenhanced and on gadolinium
      enhanced images. After application of SPIO particles, tumors became markedly
      hyperechoic and were distinctly demarcated from the surrounding brain tissue.
      CONCLUSION: SPIO particles improved the detection and demarcation of the
      experimental gliomas on sonograms, which may improve intraoperative
      neuronavigation with sonography.

PMID- 15956518
TI  - Well-circumscribed, minimally enhancing glioblastoma multiforme of the trigone: a
      case report and review of the literature.
AB  - Glioblastoma multiforme (GBM) is known to present within the lateral ventricle
      but is relatively infrequent and predominantly found in the frontal horn or body
      of the ventricle. A GBM located within the trigone is rare, and one that appears
      well-circumscribed, homogeneous, and minimally contrast enhancing, as
      demonstrated in this patient, is highly unusual.

PMID- 15956519
TI  - Automated method for generating the arterial input function on perfusion-weighted
      MR imaging: validation in patients with stroke.
AB  - BACKGROUND AND PURPOSE: The choice of arterial input function (AIF) can have a
      profound effect on the blood flow maps generated on perfusion-weighted MR imaging
      (PWI). Automation of this process could substantially reduce operator dependency,
      increase consistency, and accelerate PWI analysis. We created an automated AIF
      identification program (auto-AIF) and validated its performance against
      conventional manual methods. METHODS: We compared the auto-AIF against manually
      derived AIFs from multisection PWIs of 22 patients with stroke. Time to peak,
      curve width, curve height, and voxel location determined with both techniques
      were compared. The time to maximum of the tissue residue function (Tmax) and
      cerebral blood flow (CBF) were computed on a per-pixel basis for each AIF.
      Spatial patterns of 528 map pairs were compared by computing Pearson correlation
      coefficients between maps generated with each method. RESULTS: All auto-AIF
      derived PWI map parameters, including bolus peak, width, and height, were
      consistently superior to manually derived ones. Reproducibility of the auto-AIF
      based Tmax maps was excellent (r = 1.0). Paired Tmax maps and CBF maps from both
      techniques were well correlated (r = 0.82). Time to identify the AIF was
      significantly shorter with the auto-AIF method than with the manual technique
      (mean difference, 72 seconds; 95% confidence interval: 54, 89 seconds).
      CONCLUSION: An automated program that identifies the AIF is feasible and can
      create reliably reproducible and accurate Tmax and CBF maps. Automation of this
      process could reduce PWI analysis time and increase consistency and may allow for
      more effective use of PWI in the evaluation of acute stroke.

PMID- 15956520
TI  - Early detection of global cerebral anoxia: improved accuracy by high-b-value
      diffusion-weighted imaging with long echo time.
AB  - BACKGROUND AND PURPOSE: Early and accurate detection of global cerebral anoxia is
      important for determination of prognosis and further management. We evaluated
      whether accuracy in early detection of global cerebral anoxia was improved by
      high-b-value diffusion-weighted imaging (DWI) with long echo time (TE). METHODS:
      Routine DWI (b = 1000 s/mm(2); TE = 139 ms), high-b-value DWI (b = 3000 s/mm(2);
      TE = 190 ms), T2-weighted imaging (T2WI), and fluid-attenuated inversion recovery
      (FLAIR) imaging were acquired in six patients who experienced cardiopulmonary
      arrest within 24 hours and six volunteers. Region of interest-based analysis was
      performed. Regions of interest of patients showing significant decrease in
      apparent diffusion coefficient (ADC) values than volunteers were considered
      abnormal. Three neuroradiologists independently assessed images of the patients
      for conspicuity of hyperintensity within regions of interest. Receiver operating
      characteristic (ROC) analysis was performed, and the area under the curve (Az)
      was compared among sequences and observers. Average contrast and contrast-to
      noise ratios between abnormal regions of interest and regions of interest of
      normal surrounding parenchyma were calculated. RESULTS: For all observers, high-b
      value DWIs achieved the largest Az, and FLAIR imaging the lowest Az. Az of
      routine DWI and T2WI were between these values. High-b-value DWI and FLAIR
      imaging showed no significant interobserver variation in Az, whereas routine DWI
      and T2WI did. High-b-value DWI also achieved the largest contrast and contrast-to
      noise ratios. CONCLUSION: High-b-value DWI with long TE improved accuracy in
      early detection of global cerebral anoxia. Application of the sequence would
      facilitate early diagnosis.

PMID- 15956521
TI  - Highly diffusion-sensitized tensor imaging of unilateral cerebral arterial
      occlusive disease.
AB  - BACKGROUND AND PURPOSE: Selective neuronal death is a well-recognized
      histopathologic sequel to moderate ischemic brain damage. However, radiologic
      visualization of these changes has not been established, even with diffusion
      tensor imaging (DTI). We sought to determine whether DTI with b values > or =1900
      s/mm(2) reveals occult diffusion abnormalities in patients with cerebral arterial
      occlusive disease. METHODS: Six patients (five men, one woman; mean age +/-
      standard deviation, 66 +/- 8 years) with unilateral internal carotid or middle
      cerebral arterial occlusive disease but not parenchymal T2 hyperintensity
      underwent 3T fast DTI with b < or = 1300 s/mm(2) and slow DTI with b > or = 1900
      s/mm(2). We postprocessed mean diffusibility and fractional anisotropy (FA)
      images from the fast and slow DTI datasets. Standardized asymmetry indices (AIs)
      were used to identify regional asymmetries. Diagnostic accuracy among the DTI
      modalities was assessed by means of receiver operating characteristic analysis.
      RESULTS: In hemispheres ipsilateral to occluded vessel, AIs were significantly
      elevated on fast mean-diffusibility images of white matter at the levels of the
      internal capsule (95% confidence interval [CI]: 1.00, 1.09; P = .045) and corona
      radiata (95% CI: 1.01, 1.12; P = .034). AIs were significantly decreased on slow
      FA images at the internal capsule (95% CI: 0.84, 0.98; P = .018) and white matter
      at the internal capsule level (95% CI: 0.92, 1.00, P = .043). The slow FA map had
      the highest accuracy (89.8%) for detecting the hemisphere ipsilateral to arterial
      occlusion. CONCLUSION: Slow FA maps acquired by using DTI with high b values are
      useful for visualizing ischemic brain damage in apparently normal WM.

PMID- 15956522
TI  - Middle cerebral artery infarction: relationship of cavernous carotid artery
      calcification.
AB  - BACKGROUND AND PURPOSE: This study was designed to determine whether
      calcification of the cavernous carotid artery (CCA) is associated with
      cerebrovascular infarcts in the same way that coronary artery calcification
      scores indicate myocardial infarctions. We sought to correlate the grade of CCA
      calcification with infarctions in the middle cerebral artery (MCA) distribution.
      METHODS: Nonenhanced brain CT scans of 40 patients with MCA-distribution strokes,
      34 with non-MCA-distribution strokes, and 94 age-matched control subjects were
      reviewed. Circumferential calcification and thickness of calcification were
      graded for the CCAs on head CT scans. Scores were determined for the left and
      right CCAs. Mann-Whitney tests and Spearman correlation coefficients were used to
      detect differences between patients and control subjects and between patients
      with MCA and those with non-MCA strokes. RESULTS: CCA calcification scores did
      not significantly differ in the groups compared. The manner in which
      calcification was scored (by using circumference, thickness, or both) did not
      affect the results. No difference was noted between scores ipsilateral and those
      contralateral to the stroke. CONCLUSION: Circumferential degree or thickness of
      cavernous artery calcification was not correlated with MCA or non-MCA
      infarctions. CCA calcification scores did not differ between patients with stroke
      and those without stroke.

PMID- 15956523
TI  - Dilatation of the Virchow-Robin space is a sensitive indicator of cerebral
      microvascular disease: study in elderly patients with dementia.
AB  - BACKGROUND AND PURPOSE: Virchow-Robin spaces (VRSs) are CSF spaces that accompany
      blood vessels as they perforate the brain substance. Dilatation of VRS is
      associated with microangiopathy. Microvascular disease has a major etiologic and
      pathogenetic role in dementias. To our knowledge, no investigators have looked at
      the relationship between dilated VRS on MR imaging and cerebral microvascular
      disease. The aim of our study was to test the hypothesis that dilatation of VRS
      is associated with subcortical vascular dementia. METHODS: We recruited 75
      patients with Alzheimer's disease (n = 35), ischemic vascular dementia (n = 24),
      or frontotemporal dementia (n = 16) and 35 healthy volunteers. We assessed deep
      white matter and periventricular hyperintensities and the severity of VRS
      dilatation, as scored on MR images. Statistical group comparisons and multiple
      regression analyses were performed to quantify the relationship between imaging
      features and diagnoses. RESULTS: White matter lesions were more common in
      patients with ischemic vascular dementia than in those with Alzheimer's disease
      or healthy volunteers (P < .01). VRS scores were significantly higher in patients
      with vascular dementia than in patients with AD (P < .001), patients with FTD (P
      < .01), or healthy volunteers (P < .001). VRS scores accounted for 29% of the
      variance in the regression model, and scores for periventricular hyperintensity
      accounted for 2%. CONCLUSION: VRS dilatation is common in diseases associated
      with microvascular abnormality and can be used as a diagnostic tool to
      differentiate vascular dementias from degenerative dementias.

PMID- 15956524
TI  - A clinical example of the "limping brain" syndrome: a case report.
AB  - We present a case report of a patient presenting with persistent aphasia for 1
      week and cerebral hypoperfusion documented by single-photon emission tomography,
      both of which resolved completely after successful angioplasty of the symptomatic
      artery. This case represents a rare clinical example of "limping brain syndrome."

PMID- 15956525
TI  - Three-dimensional dynamic MR digital subtraction angiography using sensitivity
      encoding for the evaluation of intracranial arteriovenous malformations: a
      preliminary study.
AB  - BACKGROUND AND PURPOSE: Our aim was to develop 3D dynamic MR digital subtraction
      angiography with high temporal resolution without sacrificing spatial resolution
      by using sensitivity encoding for the evaluation of cerebral arteriovenous
      malformations. METHODS: Nineteen patients with 19 angiographically proven
      arteriovenous malformations (16 supratentorial and 3 infratentorial) were
      assessed by conventional catheter angiography and 3D dynamic MR digital
      subtraction angiography. A 3D contrast-enhanced gradient-echo sequence with
      sensitivity encoding based on a parallel imaging technique was performed and
      acquired 20 dynamic images, repeated 18 times every 1.7 seconds. Three
      dimensional dynamic MR digital subtraction angiograms were analyzed independently
      by two radiologists in a blinded fashion with regard to arteriovenous
      malformation nidus and venous drainage. Conventional catheter angiography was
      used as reference. RESULTS: All MR imaging examinations were assessable.
      Interobserver agreement was excellent for the detection of nidus and for the
      evaluation of nidus size (kappa = 1 and 0.875, respectively) but moderate for the
      visualization of the venous drainage (kappa = 0.56). All nidi detected on
      conventional catheter angiography were clearly depicted on 3D dynamic MR digital
      subtraction angiography. The evaluation of the size of the nidus by both
      techniques was similar. On 3D dynamic MR angiograms, veins were correctly
      analyzed in 17 of 19 arteriovenous malformations. CONCLUSION: Our preliminary
      study demonstrates that 3D dynamic MR digital subtraction angiography using
      sensitivity encoding with a high spatial resolution is appropriate for the
      assessment of arteriovenous malformations.

PMID- 15956526
TI  - Retrograde cortical and deep venous drainage in patients with intracranial dural
      arteriovenous fistulas: comparison of MR imaging and angiographic findings.
AB  - BACKGROUND AND PURPOSE: We assessed MR imaging, specifically contrast-enhanced
      three-dimensional (3D) magnetization-prepared rapid gradient-echo (MP-RAGE), in
      evaluating retrograde venous drainage in patients with intracranial dural
      arteriovenous fistulas (dAVFs) that may result in catastrophic venous infarction
      or hemorrhage. METHODS: Twenty-one patients with angiographically proved dAVFs
      underwent nonenhanced spin-echo (SE) and fast SE imaging, 3D fast imaging with
      steady-state precession, and enhanced SE and 3D MP-RAGE imaging. Retrograde
      venous drainage was categorized as cerebral cortical, deep cerebral, posterior
      fossa medullary, ophthalmic, or spinal venous. We assessed retrograde venous
      drainage and graded its severity. MR imaging and angiographic severities were
      correlated. Sensitivity, specificity, and accuracy were calculated to evaluate
      the diagnostic utility of each technique compared with conventional angiography.
      We retrospectively correlated angiograms and MR images. RESULTS: Enhanced 3D MP
      RAGE and T1-weighted SE images had higher diagnostic accuracy higher than
      nonenhanced images, especially when retrograde drainage involved cerebral
      cortical, posterior fossa, and spinal veins. Correlation of severity for enhanced
      MP-RAGE images and enhanced T1-weighted images with angiograms was good to
      excellent and better than that with nonenhanced images. All sequences had low
      diagnostic accuracy when drainage was via deep cerebral veins. On retrospective
      review, 3D MP-RAGE images showed two thrombotic inferior petrosal sinuses.
      CONCLUSION: Enhanced MR images were superior to nonenhanced images in assessing
      retrograde venous drainage in intracranial dAVFs. Enhanced 3D MP-RAGE is superior
      to enhanced T1-weighted SE imaging for determining the route and severity of
      venous reflux because of its increased spatial resolution and ability to
      contiguously delineate the venous system.

PMID- 15956527
TI  - Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis
      lesions: characterizing hemodynamic impairment and inflammatory activity.
AB  - BACKGROUND AND PURPOSE: Perfusion measurement in multiple sclerosis (MS) may cast
      light on the disease pathogenesis and lesion development since vascular pathology
      is frequently demonstrated in the disease. This study was performed to
      investigate the perfusion characteristics in MS lesions using dynamic
      susceptibility contrast MR imaging (DSC-MRI) to better understand the hemodynamic
      changes in MS. METHODS: Seventeen patients with relapsing-remitting MS were
      studied with DSC-MRI. Perfusion measurements included cerebral blood flow (CBF),
      cerebral blood volume (CBV), and mean transit time (MTT), were obtained in
      enhancing, non-enhancing lesions covered by DSC-MRI and contralateral normal
      appearing white matter (NAWM) in patients as well as normal white matter in
      seventeen control subjects. RESULTS: DSC-MRI data demonstrated reduced perfusion
      with significantly prolonged MTT (P < 0.001) in lesions and NAWM in patients
      compared with normal white matter in controls. Compared to contralateral NAWM,
      enhancing lesions demonstrate increased CBF (P = 0.007) and CBV (P < 0.0001),
      indicating inflammation-mediated vasodilatation. A K means cluster analysis was
      performed and identifies approximately 63.8% of non-enhancing lesions (Class 1)
      with significantly decreased perfusion (P < or = 0.0001) when compared with
      contralateral NAWM. In contrast, the remainder 36.2% non-enhancing lesions (Class
      2) show increased CBV (P = 0.02) in a similar fashion to enhancing lesions and
      can be observed on quantitative color-coded maps even without blood-brain barrier
      breakdown. CONCLUSION: DSC-MRI measurements demonstrate potential for
      investigating hemodynamic abnormalities that are associated with inflammatory
      activity, lesion reactivity and vascular compromise in MS lesions. Non-enhancing
      lesions showed both low and high perfusion suggesting microvascular abnormalities
      with hemodynamic impairment and inflammatory reactivity that cannot be seen on
      conventional MRI.

PMID- 15956528
TI  - Anti-tumor necrosis factor alpha-associated multiple sclerosis.
AB  - A case of multiple sclerosis presenting during anti-tumor necrosis factor
      treatment for rheumatoid arthritis is discussed. This association has been
      reported in the nonradiological literature, but is an important association for
      radiologists to be aware of, as they may be in a position to first suggest the
      diagnosis.

PMID- 15956529
TI  - Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt
      Jakob disease: high sensitivity and specificity for diagnosis.
AB  - BACKGROUND AND PURPOSE: Abnormalities on diffusion-weighted images (DWIs) and
      fluid-attenuated inversion recovery (FLAIR) images are reported in Creutzfeldt
      Jakob disease (CJD). To our knowledge, no large study has been conducted to
      determine the sensitivity and specificity of DWI and FLAIR imaging for diagnosing
      CJD. METHODS: Two neuroradiologists, blinded to diagnosis, retrospectively
      evaluated DWI and FLAIR images from 40 patients with probable or definite CJD and
      53 control subjects with other forms of dementia and rated the likelihood of CJD
      on the basis of the imaging findings. RESULTS: DWI and FLAIR imaging was 91%
      sensitive, 95% specific, and 94% accurate for CJD. Interrater reliability was
      high (kappa = 0.93). Sensitivity was higher for DWI than FLAIR imaging.
      Abnormalities involved cortex and deep gray matter (striatum and/or thalamus) in
      68% of patients with CJD, cortex alone in 24%, and deep gray matter alone in 5%.
      The most typical and specific patterns were corresponding hyperintensity on both
      FLAIR images and DWIs confined to the gray matter in the cortex, striatum, medial
      and/or posterior thalamus, or a combination of these areas. Narrow-window soft
      copy review of artifact-free DWIs and FLAIR images and recognition of the normal
      variation in cortical signal intensity proved critical for successful
      differentiation of CJD from other dementias. CONCLUSION: Because specific
      patterns of abnormality on DWI and FLAIR images are highly sensitive and specific
      for CJD, these sequences should be performed whenever CJD is suspected.

PMID- 15956530
TI  - Cerebral perfusion alterations during the acute phase of experimental generalized
      status epilepticus: prediction of survival by using perfusion-weighted MR imaging
      and histopathology.
AB  - BACKGROUND AND PURPOSE: Persistent generalized status epilepticus (SE) is
      associated with alterations of cerebral perfusion (CP). Because perfusion
      weighted MR imaging (PWI) allows noninvasive CP-determination, the aim of this
      study was to investigate CP alterations during acute experimental SE correlated
      with SE-induced neuronal cell loss. METHODS: The rat pilocarpine model was used
      to induce SE. Multilocal PWI was performed before (baseline) and 3, 15, 30, 60,
      and 120 minutes after onset of SE. Bolus-peak ratio (BPR) was calculated for the
      retrosplenial and piriform cortex, hippocampus, amygdala, and thalamus and
      compared with baseline. Neuronal cell loss was quantified at different time
      points after induction of SE by cresyle violet staining. RESULTS: Immediately
      after SE onset (3 minutes), BPR temporarily increased to 102%-130% in all
      regions, with a maximum in the amygdala (129 +/- 16%) and hippocampus (130 +/-
      21%). At 15, 30, and 60 minutes, BPR decreased continuously to 57%-76%. BPR
      values <55% in the parietal and/or temporal cortex resulted in death. In
      surviving animals, BPR recovered to 66%-79% and there was a good correlation
      between neuronal cell loss in specific brain regions at 2 weeks after SE onset
      and maximal decrease in BPR (r > 0.73). CONCLUSION: PWI demonstrated a transient
      cerebral hyperperfusion immediately after SE onset, followed by a significant
      continuous decline to different perfusion levels. In our experimental setting, a
      decline of cortical BPR below 55% of baseline seems to be a prognostic threshold
      value associated with subsequent death. In surviving animals, there is good
      correlation between the maximal decrease in BPR in the acute phase of SE and late
      neuronal cell loss.

PMID- 15956531
TI  - 1H MR spectroscopic characteristics of kernicterus: a possible metabolic
      signature.
AB  - BACKGROUND AND PURPOSE: MR examination of infants with kernicterus shows abnormal
      changes in signal intensity in various parts of the brain, including the globus
      pallidus and subthalamic regions. The purpose of this study was to
      retrospectively analyze proton ((1)H) MR spectroscopic data to see if the MR
      spectroscopic profiles of infants with hyperbilirubinemia and symptoms of
      kernicterus provide new insights into the pathophysiology of bilirubin
      neurotoxicity. METHODS: Six patients aged 3 days to 3 weeks, with
      hyperbilirubinemia and symptoms of kernicterus underwent MR imaging and MR
      spectroscopy with a single-voxel point-resolved spectroscopic sequence. The voxel
      of interest was centered in the basal ganglia with CSF excluded. Quantitative
      analysis was done by using LCModel. Between-subject comparisons were based on
      metabolite ratios relative to creatine. RESULTS: Ratios of taurine, glutamate and
      glutamine, and myoinositol relative to creatine were significantly elevated (P <
      .001), whereas the ratio of choline to creatine was significantly decreased (P <
      .001) compared with normal values published for this age group. Lactate levels
      were not significantly elevated. CONCLUSION: Kernicterus has a characteristic
      signature that is detectable on (1)H-MR spectroscopy. Our results are generally
      in agreement with what is known about bilirubin pathology, and the finding of
      increased glutamate and glutamine and decreased choline ratios indicates a
      possible link between hepatic encephalopathy and kernicterus. This observation
      may help in elucidating the pathophysiology of bilirubin neurotoxicity.

PMID- 15956532
TI  - Nasopharyngeal carcinoma: recognizing the radiographic features in children.
AB  - BACKGROUND AND PURPOSE: Children often present with enlargement of the
      nasopharyngeal soft tissues, which is usually due to benign hypertrophy of
      adenoids. The objective of this report is to emphasize that, although rare,
      nasopharyngeal carcinoma (NPC) does occur in children and can be diagnosed
      reliably when certain key radiographic features are recognized. METHODS: The
      presenting scans of 11 patients with biopsy proven NPC were reviewed
      retrospectively by a CAQ-certified neuroradiologist. The age range was 12-17
      years (median 15 years). Fifteen scans were reviewed, including 8 CT scans of the
      neck with intravenous contrast and 7 MR scans of the nasopharynx without and with
      gadolinium. RESULTS: All 11 patients had a nasopharyngeal mass. The
      nasopharyngeal mass had invaded the central skull base in 10 patients (91%).
      Widening of the petroclival fissure was present in 8 (73%) patients; all except
      one patient had accompanying skull base invasion. The tumor had extended into the
      adjacent parapharyngeal space in 6 (55%), the pterygopalatine fossa in 2 (18%),
      and the masticator space in 2 (18%). Unilateral cervical lymphadenopathy was
      present in 4 (36%) and bilateral in 7 (64%). Lateral retropharyngeal
      lymphadenopathy that measured greater than 1 cm in maximal transverse dimension
      was present in 10 (91%). CONCLUSION: Pediatric NPC is generally not suspected
      clinically until late into the disease process. Awareness that NPC can occur in
      children should prompt careful evaluation for distinctive radiographic features.
      Earlier diagnosis may then direct the patient to timely appropriate therapy when
      these key radiographic features are present and recognized.

PMID- 15956533
TI  - Diffuse cortical necrosis in a neonate with incontinentia pigmenti and an
      encephalitis-like presentation.
AB  - Incontinentia pigmenti is a rare neurocutaneous disorder that may present with
      neurologic symptoms, in addition to a characteristic vesicular rash within the
      first days of life. We describe a neonate girl presenting with a rash and an
      encephalopathy who was first thought to suffer from a viral infection and was
      only later recognized as being affected by incontinentia pigmenti. Cerebral MR
      imaging showed extensive cortical necrosis in the acute period. Incontinentia
      pigmenti should be included in the differential diagnosis of encephalopathy and
      cutaneous involvement in neonates, after a viral infection has been ruled out.

PMID- 15956534
TI  - Diffusion tensor imaging in lissencephaly.
AB  - Lissencephaly is a rare brain malformation characterized histologically by
      arrested neuronal migration such that the brain resembles that of a fetus before
      23-24 weeks gestation. We studied a neonate with lissencephaly by using diffusion
      tensor imaging and suggest the dysplastic densely cellular layer IV is visible as
      a band of anisotropic diffusion. Fiber tracking showed lack of connectivity
      between the cortex and deep white matter and an abnormal limbic system.

PMID- 15956535
TI  - MR diffusion tensor imaging and fiber tracking in spinal cord compression.
AB  - BACKGROUND AND PURPOSE: Spinal cord damage can result in major functional
      disability. Alteration of the spinal cord structural integrity can be assessed by
      using diffusion tensor imaging methods. Our objective is to evaluate the
      diagnostic accuracy of apparent diffusion coefficient (ADC), fractional
      anisotropy (FA), and fiber tracking in both acute and slowly progressive spinal
      cord compressions. METHODS: Fifteen patients with clinical symptoms of acute (n =
      2) or slowly progressive (n = 13) spinal cord compression and 11 healthy
      volunteers were prospectively selected. We performed T2-weighted fast spin echo
      (FSE) and diffusion tensor imaging by using a 1.5-T MR scanner. ADC and FA maps
      were computed. Regions of interest were placed at the cervical, upper and lower
      thoracic cord levels for the healthy subjects and on the area with abnormal T2
      weighted signal intensity in the patients with cord compression. In three
      patients, we used fiber tracking to locate the areas of cord compression
      precisely. Data were analyzed by using a mixed model. The sensitivity (SE) and
      specificity (sp) of imaging (T2, ADC, and FA maps) in the detection of spinal
      cord abnormality were statistically evaluated. RESULTS: For the healthy subjects,
      averaged ADC values ranged from 0.96 10(-3) mm(2)/s to 1.05 10(-3) mm(2)/s and
      averaged FA values ranged from 0.745 to 0.751. Ten patients had decreased FA
      (0.67 +/- 0.087), and one had increased FA values (0.831); only two patients had
      increased ADC values (1.03 +/- 0.177). There was a statistically significant
      difference in the FA values between volunteers and patients (P = .012). FA had a
      much higher sensitivity (SE = 73.3%) and specificity (sp = 100%) in spinal cord
      abnormalities detection compared with T2-weighted FSE imaging (se = 46.7%, sp =
      100%) and ADC (SE = 13.4%, sp = 80%). CONCLUSIONS: FA has the highest sensitivity
      and specificity in the detection of acute spinal cord abnormalities. Spinal cord
      fiber tracking is a useful tool to focus measurements on the compressed spinal
      cord.

PMID- 15956536
TI  - MRI findings after successful vertebroplasty.
AB  - BACKGROUND AND PURPOSE: Recurrent or residual back pain after vertebroplasty (VP)
      is common, and many patients with these symptoms are evaluated by MRI. The
      purpose of this report is to describe post-treatment MRI findings after
      successful VP. METHODS: We identified all patients who underwent VP at our
      institution and later presented with back pain and had a spine MRI. From these
      patients, we identified a cohort with uncomplicated procedures, in whom back pain
      at the site of the VP was not the dominant pain source at follow-up. Using the
      pre- and postoperative MRIs and the VP conventional radiographs, we assessed such
      features as interval height loss and changes in marrow edema in treated
      vertebrae. RESULTS: Thirty patients (51 treated vertebrae) met our clinical
      criteria for uncomplicated VP. Nine (18%) of 51 vertebrae lost additional height
      after the procedure. Neither patient demographics nor variables associated with
      the procedure itself, including volume of cement injected, correlated with
      additional height loss after VP. Moderate or severe marrow edema was demonstrated
      in 62% of vertebrae on preoperative MRI and in 33% of vertebrae on follow-up MRI.
      Twenty-one percent of vertebrae had new areas of marrow edema on follow-up.
      Twenty-two percent of vertebrae imaged >6 months after VP had moderate or severe
      edema. CONCLUSION: Progressive and persistent edema and interval height loss
      after successful VP are common and should not be interpreted as sufficient
      evidence of ongoing pathology at the treated vertebral level.

PMID- 15956537
TI  - New symptomatic vertebral compression fractures within a year following
      vertebroplasty in osteoporotic women.
AB  - BACKGROUND AND PURPOSE: Percutaneous vertebroplasty has been performed in the
      United States in an increasing volume since the mid-1990s. The purpose of this
      study is to analyze the risk of a new symptomatic vertebral compression fractures
      within 1 year of having an acute/subacute fracture treated with vertebroplasty.
      METHODS: A retrospective analysis was performed in which 253 female patients were
      found to have acute/subacute vertebral compression fractures secondary to
      osteoporosis treated with percutaneous vertebroplasty. Occurrences of new
      symptomatic vertebral compression fractures were recorded for a year following
      initial vertebroplasty. RESULTS: Fifty-five patients (21.7%) of the 253
      osteoporotic women with one or more initial fractures experienced a new
      symptomatic vertebral compression fracture within 1 year. CONCLUSION: Roughly one
      fifth of osteoporotic women with acute/subacute fracture treated with
      vertebroplasty will have a subsequent fracture within 1 year.

PMID- 15956538
TI  - Transient infundibular mass associated with temporary functional deficiency.

PMID- 15956541
TI  - RNA replication without RNA-dependent RNA polymerase: surprises from hepatitis
      delta virus.

PMID- 15956542
TI  - Compartmentalized human immunodeficiency virus type 1 present in cerebrospinal
      fluid is produced by short-lived cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system
      (CNS) during primary infection and persists in this compartment by unknown
      mechanisms over the course of infection. In this study, we examined viral
      population dynamics in four asymptomatic subjects commencing antiretroviral
      therapy to characterize cellular sources of HIV-1 in the CNS. The inability to
      monitor viruses directly in the brain poses a major challenge in studying HIV-1
      dynamics in the CNS. Studies of HIV-1 in cerebrospinal fluid (CSF) provide a
      useful surrogate for the sampling of virus in the CNS, but they are complicated
      by the fact that infected cells in local CNS tissues and in the periphery
      contribute to the population pool of HIV-1 in CSF. We utilized heteroduplex
      tracking assays to differentiate CSF HIV-1 variants that were shared with
      peripheral blood plasma from those that were compartmentalized in CSF and
      therefore presumably derived from local CNS tissues. We then tracked the relative
      decline of individual viral variants during the initial days of antiretroviral
      therapy. We found that HIV-1 variants compartmentalized in CSF declined rapidly
      during therapy, with maximum half-lives of approximately 1 to 3 days. These
      kinetics emulate the decline in HIV-1 produced from short-lived CD4+ T cells in
      the periphery, suggesting that a similarly short-lived, HIV-infected cell
      population exists within the CNS. We propose that short-lived CD4+ T cells
      trafficking between the CNS and the periphery play an important role in
      amplifying and maintaining HIV-1 populations in the CNS during the asymptomatic
      phase of infection.

PMID- 15956543
TI  - Junctional adhesion molecule a serves as a receptor for prototype and field
      isolate strains of mammalian reovirus.
AB  - Reovirus infections are initiated by the binding of viral attachment protein
      sigma1 to receptors on the surface of host cells. The sigma1 protein is an
      elongated fiber comprised of an N-terminal tail that inserts into the virion and
      a C-terminal head that extends from the virion surface. The prototype reovirus
      strains type 1 Lang/53 (T1L/53) and type 3 Dearing/55 (T3D/55) use junctional
      adhesion molecule A (JAM-A) as a receptor. The C-terminal half of the T3D/55
      sigma1 protein interacts directly with JAM-A, but the determinants of receptor
      binding specificity have not been identified. In this study, we investigated
      whether JAM-A also mediates the attachment of the prototype reovirus strain type
      2 Jones/55 (T2J/55) and a panel of field-isolate strains representing each of the
      three serotypes. Antibodies specific for JAM-A were capable of inhibiting
      infections of HeLa cells by T1L/53, T2J/55, and T3D/55, demonstrating that
      strains of all three serotypes use JAM-A as a receptor. To corroborate these
      findings, we introduced JAM-A or the structurally related JAM family members JAM
      B and JAM-C into Chinese hamster ovary cells, which are poorly permissive for
      reovirus infection. Both prototype and field-isolate reovirus strains were
      capable of infecting cells transfected with JAM-A but not those transfected with
      JAM-B or JAM-C. A sequence analysis of the sigma1-encoding S1 gene segment of the
      strains chosen for study revealed little conservation in the deduced sigma1 amino
      acid sequences among the three serotypes. This contrasts markedly with the
      observed sequence variability within each serotype, which is confined to a small
      number of amino acids. Mapping of these residues onto the crystal structure of
      sigma1 identified regions of conservation and variability, suggesting a likely
      mode of JAM-A binding via a conserved surface at the base of the sigma1 head
      domain.

PMID- 15956544
TI  - A cellular Drosophila melanogaster protein with similarity to baculovirus F
      envelope fusion proteins.
AB  - Baculovirus F (fusion) proteins are found in the envelopes of budded virions.
      Recently a Drosophila melanogaster gene (CG4715) that encodes a protein with
      sequence similarity to baculovirus F proteins was discovered. To examine
      similarities and differences with baculovirus F proteins, we cloned the D.
      melanogaster cellular F (Dm-cF) protein gene and analyzed Dm-cF expression and
      localization. The predicted Dm-cF protein sequence lacks a furin cleavage site,
      and transiently expressed Dm-cF showed no protein cleavage and no detectable
      membrane fusion activity. In cell localization studies, transiently expressed Dm
      cF was localized to intracellular organelles in D. melanogaster S2 cells, unlike
      baculovirus F proteins, which localize to cellular plasma membranes. Using
      reverse transcriptase PCR and Western blot analysis to examine Dm-cF expression
      in animals, we detected Dm-cF expression in both larval and adult D. melanogaster
      cells. However, Dm-cF expression was detected only in third instar larvae and
      adults, suggesting that Dm-cF expression may be developmentally regulated. We
      also identified genes related to Dm-cF in the genomes of two other Drosophila
      species, Drosophila yakuba and Drosophila pseudoobscura, and the mosquito
      Anopheles gambiae. These observations suggest that f genes may be present in the
      genomes of many insects. Conservation within and between 22 baculovirus and 4
      insect F proteins was examined in detail. These studies demonstrate that Dm-cF is
      expressed in D. melanogaster and suggest that if baculovirus f genes are derived
      from a host cellular f gene, the function appears to have changed substantially
      upon adaptation to the baculovirus infection cycle.

PMID- 15956545
TI  - Human immunodeficiency virus type 1 Vpr impairs dendritic cell maturation and T
      cell activation: implications for viral immune escape.
AB  - Antigen presentation and T-cell activation are dynamic processes involving
      signaling molecules present in both APCs and T cells. Effective APC function and
      T-cell activation can be compromised by viral immune evasion strategies,
      including those of human immunodeficiency virus type 1 (HIV-1). In this study, we
      determined the effects of HIV-1 Vpr on one of the initial target of the virus,
      dendritic cells (DC), by investigating DC maturation, cytokine profiling, and CD8
      specific T-cell stimulation function followed by a second signal. Vpr impaired
      the expression of CD80, CD83, and CD86 at the transcriptional level without
      altering normal cellular transcription. Cytokine profiling indicated that the
      presence of Vpr inhibited production of interleukin 12 (IL-12) and upregulated IL
      10, whereas IL-6 and IL-1beta were unaltered. Furthermore, DC infected with HIV-1
      vpr+ significantly reduced the activation of antigen-specific memory and recall
      cytotoxic-T-lymphocyte responses. Taken together, these results indicate that HIV
      1 Vpr may in part be responsible for HIV-1 immune evasion by inhibiting the
      maturation of costimulatory molecules and cytokines essential for immune
      activation.

PMID- 15956546
TI  - Inhibition of alpha/beta interferon signaling by the NS4B protein of
      flaviviruses.
AB  - Flaviviruses are insect-borne, positive-strand RNA viruses that have been
      disseminated worldwide. Their genome is translated into a polyprotein, which is
      subsequently cleaved by a combination of viral and host proteases to produce
      three structural proteins and seven nonstructural proteins. The nonstructural
      protein NS4B of dengue 2 virus partially blocks activation of STAT1 and
      interferon-stimulated response element (ISRE) promoters in cells stimulated with
      interferon (IFN). We have found that this function of NS4B is conserved in West
      Nile and yellow fever viruses. Deletion analysis shows that that the first 125
      amino acids of dengue virus NS4B are sufficient for inhibition of alpha/beta IFN
      (IFN-alpha/beta) signaling. The cleavable signal peptide at the N terminus of
      NS4B, a peptide with a molecular weight of 2,000, is required for IFN antagonism
      but can be replaced by an unrelated signal peptide. Coexpression of dengue virus
      NS4A and NS4B together results in enhanced inhibition of ISRE promoter activation
      in response to IFN-alpha/beta. In contrast, expression of the precursor NS4A/B
      fusion protein does not cause an inhibition of IFN signaling unless this product
      is cleaved by the viral peptidase NS2B/NS3, indicating that proper viral
      polyprotein processing is required for anti-interferon function.

PMID- 15956547
TI  - Pyrrolidine dithiocarbamate reduces coxsackievirus B3 replication through
      inhibition of the ubiquitin-proteasome pathway.
AB  - Coxsackievirus B3 (CVB3) is one of the most common pathogens for viral
      myocarditis. The lack of effective therapeutics for CVB3-caused viral diseases
      underscores the importance of searching for antiviral compounds. Pyrrolidine
      dithiocarbamate (PDTC) is an antioxidant and is recently reported to inhibit
      ubiquitin-proteasome-mediated proteolysis. Previous studies have shown that PDTC
      inhibits replication of rhinovirus, influenza virus, and poliovirus. In the
      present study, we report that PDTC is a potent inhibitor of CVB3. Coxsackievirus
      infected HeLa cells treated with PDTC showed a significant reduction of CVB3
      viral RNA synthesis, viral protein VP1 expression, and viral progeny release.
      Similar to previous observation that divalent ions mediate the function of PDTC,
      we further report that serum-containing copper and zinc are required for its
      antiviral activity. CVB3 infection resulted in massive generation of reactive
      oxygen species (ROS). Although PDTC alleviated ROS generation, the antiviral
      activity was unlikely dependent on its antioxidant effect because the potent
      antioxidant, N-acetyl-L-cysteine, failed to inhibit CVB3 replication. Consistent
      with previous reports that PDTC inhibits ubiquitin-proteasome-mediated protein
      degradation, we found that PDTC treatment led to the accumulation of several
      short-lived proteins in infected cells. We further provide evidence that the
      inhibitory effect of PDTC on protein degradation was not due to inhibition of
      proteasome activity but likely modulation of ubiquitination. Together with our
      previous findings that proteasome inhibition reduces CVB3 replication (H. Luo, J.
      Zhang, C. Cheung, A. Suarez, B. M. McManus, and D. Yang, Am. J. Pathol. 163:381
      385, 2003), results in this study suggest a strong antiviral effect of PDTC on
      coxsackievirus, likely through inhibition of the ubiquitin-proteasome pathway.

PMID- 15956548
TI  - Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirus boost
      immunization to human immunodeficiency virus Env and Gag immunogens.
AB  - A variety of gene-based vaccination approaches have been used to enhance the
      immune response to viral pathogens. Among them, the ability to perform
      heterologous immunization by priming with DNA and boosting with replication
      defective adenoviral (ADV) vectors encoding foreign antigens has proven
      particularly effective in eliciting enhanced cellular and humoral immunity
      compared to either agent alone. Because adenoviral vector immunization alone can
      elicit substantial cellular and humoral immune responses in a shorter period of
      time, we asked whether the immune response induced by the prime-boost
      immunization was different from adenoviral vaccines with respect to the potency
      and breadth of T-cell recognition. While DNA/ADV immunization stimulated the CD8
      response, it was directed to the same epitopes in Gag and Env immunogens of human
      immunodeficiency virus as DNA or ADV alone. In contrast, the CD4 response to
      these immunogens diversified after DNA/ADV immunization compared to each vector
      alone. These findings suggest that the diversity of the CD4 immune response is
      increased by DNA/ADV prime-boost vaccination and that these components work
      synergistically to enhance T-cell epitope recognition.

PMID- 15956550
TI  - Effects of a temperature sensitivity mutation in the J1R protein component of a
      complex required for vaccinia virus assembly.
AB  - Vaccinia virus J1R protein is required for virion morphogenesis (W. L. Chiu and
      W. Chang, J. Virol. 76:9575-9587, 2002). In this work, we further characterized
      the J1R protein of wild-type vaccinia virus and compared it with the protein
      encoded by the temperature-sensitive mutant virus Cts45. The mutant Cts45 was
      found to contain a Pro-to-Ser substitution at residue 132 of the J1R open reading
      frame, which is responsible for a loss-of-function phenotype. The half-life of
      the J1R-P132S mutant protein was comparable at both 31 and 39 degrees C,
      indicating that the P132S mutation did not affect the stability of the J1R
      protein. We also showed that the J1R protein interacts with itself in the virus
      infected cells. The N-terminal region of the J1R protein, amino acids (aa) 1 to
      77, interacted with the C-terminal region, aa 84 to 153, and the P132 mutation
      did not abolish this interaction, as determined by two-hybrid analysis.
      Furthermore, we demonstrated that J1R protein is part of a viral complex
      containing the A30L, G7L, and F10L proteins in virus-infected cells. In
      immunofluorescence analyses, wild-type J1R protein colocalized with the A30L,
      G7L, and F10L proteins in virus-infected cells but the loss-of-function P132
      mutant did not. Furthermore, without a functional J1R protein, rapid degradation
      of A30L and the 15-kDa forms of the G7L and F10L proteins was observed in cells
      infected with Cts45 at 39 degrees C. This study thus demonstrated the importance
      of the J1R protein in the formation of a viral assembly complex required for
      morphogenesis.

PMID- 15956549
TI  - Investigation by atomic force microscopy of the structure of Ty3 retrotransposon
      particles.
AB  - Ty3, a member of the Metaviridiae family of long-terminal-repeat retrotransposons
      found in Saccharomyces cerevisiae, encodes homologs of retroviral Gag and Gag-Pol
      proteins, which, together with genomic RNA, assemble into virus-like particles
      (VLPs) that undergo processing and reverse transcription. The Ty3 structural
      proteins, capsid and nucleocapsid, contain major homology and nucleocapsid motifs
      similar to retrovirus capsid and nucleocapsid proteins, but Ty3 lacks a matrix
      like structural domain amino terminal to capsid. Mass spectrometry analysis of
      Ty3 Gag3 processing products defined an acetylated Ser residue as the amino
      terminus of Gag3/p34, p27, and CA/p24 species and supported a model where p34 and
      p27 occur in phosphorylated forms. Using atomic force microscopy, VLPs were
      imaged from cells producing wild-type and protease and reverse transcriptase
      mutant Ty3. Wild-type VLPs were found to have a broad range of diameters, but the
      majority, if not all of the particles, exhibited arrangements of capsomeres on
      their surfaces which were consistent with icosahedral symmetry. Wild-type
      particles were in the range of 25 to 52 nm in diameter, with particles in the 42-
      to 52-nm diameter range consistent with T=7 symmetry. Both classes of mutant VLPs
      fell into a narrower range of 44 to 53 nm in diameter and appeared to be
      consistent with T=7 icosahedral symmetry. The smaller particles in the wild-type
      population likely correspond to VLPs that have progressed to reverse
      transcription or later stages, which do not occur in the protease and reverse
      transcriptase mutants. Ty3 VLPs did not undergo major external rearrangements
      during proteolytic maturation.

PMID- 15956551
TI  - Regulation of the translation initiation factor eIF4F by multiple mechanisms in
      human cytomegalovirus-infected cells.
AB  - As a viral opportunistic pathogen associated with serious disease among the
      immunocompromised and congenital defects in newborns, human cytomegalovirus
      (HCMV) must engage the translational machinery within its host cell to synthesize
      the viral proteins required for its productive growth. However, unlike many
      viruses, HCMV does not suppress the translation of host polypeptides. Here, we
      examine how HCMV regulates the cellular cap recognition complex eIF4F, a critical
      component of the cellular translation initiation apparatus that recruits the 40S
      ribosome to the 5' end of the mRNA. This study establishes that the cap binding
      protein eIF4E, together with the translational repressor 4E-BP1, are both
      phosphorylated early in the productive viral growth cycle and that the activity
      of the cellular eIF4E kinase, mnk, is critical for efficient viral replication.
      Furthermore, HCMV replication also induces an increase in the overall abundance
      of eIF4F components and promotes assembly of eIF4F complexes. Notably, increasing
      the abundance of select eIF4F core components and associated factors alters the
      ratio of active eIF4F complexes in relation to the 4E-BP1 translational
      repressor, illustrating a new strategy through which members of the herpesvirus
      family enhance eIF4F activity during their replicative cycle.

PMID- 15956552
TI  - Gene 5 of the avian coronavirus infectious bronchitis virus is not essential for
      replication.
AB  - The avian coronavirus Infectious bronchitis virus (IBV), like other
      coronaviruses, expresses several small nonstructural (ns) proteins in addition to
      those from gene 1 (replicase) and the structural proteins. These coronavirus ns
      genes differ both in number and in amino acid similarity between the coronavirus
      groups but show some concordance within a group or subgroup. The functions and
      requirements of the small ns gene products remain to be elucidated. With the
      advent of reverse genetics for coronaviruses, the first steps in elucidating
      their role can be investigated. We have used our reverse genetics system for IBV
      (R. Casais, V. Thiel, S. G. Siddell, D. Cavanagh, and P. Britton, J. Virol.
      75:12359-12369, 2001) to investigate the requirement of IBV gene 5 for
      replication in vivo, in ovo, and ex vivo. We produced a series of recombinant
      viruses, with an isogenic background, in which complete expression of gene 5
      products was prevented by the inactivation of gene 5 following scrambling of the
      transcription-associated sequence, thereby preventing the expression of IBV
      subgenomic mRNA 5, or scrambling either separately or together of the translation
      initiation codons for the two gene 5 products. As all of the recombinant viruses
      replicated very similarly to the wild-type virus, Beau-R, we conclude that the
      IBV gene 5 products are not essential for IBV replication per se and that they
      are accessory proteins.

PMID- 15956553
TI  - Hepatitis C virus E2-CD81 interaction induces hypermutation of the immunoglobulin
      gene in B cells.
AB  - Hepatitis C virus (HCV) is one of the leading causes of chronic liver diseases
      and B-lymphocyte proliferative disorders, including mixed cryoglobulinemia and B
      cell lymphoma. It has been suggested that HCV infects human cells through the
      interaction of its envelope glycoprotein E2 with a tetraspanin molecule CD81, the
      putative viral receptor. Here, we show that the engagement of B cells by purified
      E2 induced double-strand DNA breaks specifically in the variable region of
      immunoglobulin (V(H)) gene locus, leading to hypermutation in the V(H) genes of B
      cells. Other gene loci were not affected. Preincubation with the anti-CD81
      monoclonal antibody blocked this effect. E2-CD81 interaction on B cells triggered
      the enhanced expression of activation-induced cytidine deaminase (AID) and also
      stimulated the production of tumor necrosis factor alpha. Knockdown of AID by the
      specific small interfering RNA blocked the E2-induced double-strand DNA breaks
      and hypermutation of the V(H) gene. These findings suggest that HCV infection,
      through E2-CD81 interaction, may modulate host's innate or adaptive immune
      response by activation of AID and hypermutation of immunoglobulin gene in B
      cells, leading to HCV-associated B-cell lymphoproliferative diseases.

PMID- 15956554
TI  - Extensive syncytium formation mediated by the reovirus FAST proteins triggers
      apoptosis-induced membrane instability.
AB  - The fusion-associated small transmembrane (FAST) proteins of the fusogenic
      reoviruses are the only known examples of membrane fusion proteins encoded by non
      enveloped viruses. While the involvement of the FAST proteins in mediating
      extensive syncytium formation in virus-infected and -transfected cells is well
      established, the nature of the fusion reaction and the role of cell-cell fusion
      in the virus replication cycle remain unclear. To address these issues, we
      analyzed the syncytial phenotype induced by four different FAST proteins: the
      avian and Nelson Bay reovirus p10, reptilian reovirus p14, and baboon reovirus
      p15 FAST proteins. Results indicate that FAST protein-mediated cell-cell fusion
      is a relatively non-leaky process, as demonstrated by the absence of significant
      [3H]uridine release from cells undergoing fusion and by the resistance of these
      cells to treatment with hygromycin B, a membrane-impermeable translation
      inhibitor. However, diminished membrane integrity occurred subsequent to
      extensive syncytium formation and was associated with DNA fragmentation and
      chromatin condensation, indicating that extensive cell-cell fusion activates
      apoptotic signaling cascades. Inhibiting effector caspase activation or ablating
      the extent of syncytium formation, either by partial deletion of the avian
      reovirus p10 ecto-domain or by antibody inhibition of p14-mediated cell-cell
      fusion, all resulted in reduced membrane permeability changes. These observations
      suggest that the FAST proteins do not possess intrinsic membrane-lytic activity.
      Rather, extensive FAST protein-induced syncytium formation triggers an apoptotic
      response that contributes to altered membrane integrity. We propose that the FAST
      proteins have evolved to serve a dual role in the replication cycle of these
      fusogenic non-enveloped viruses, with non-leaky cell-cell fusion initially
      promoting localized cell-cell transmission of the infection followed by enhanced
      progeny virus release from apoptotic syncytia and systemic dissemination of the
      infection.

PMID- 15956555
TI  - Role of the hypervariable hinge region of phosphoprotein P of vesicular
      stomatitis virus in viral RNA synthesis and assembly of infectious virus
      particles.
AB  - The phosphoprotein (P protein) of vesicular stomatitis virus (VSV) is an
      essential subunit of the viral RNA-dependent RNA polymerase and has multiple
      functions residing in its different domains. In the present study, we examined
      the role of the hypervariable hinge region of P protein in viral RNA synthesis
      and recovery of infectious VSV by using transposon-mediated insertion mutagenesis
      and deletion mutagenesis. We observed that insertions of 19-amino-acid linker
      sequences at various positions within this region affected replication and
      transcription functions of the P protein to various degrees. Interestingly, one
      insertion mutant was completely defective in both transcription and replication.
      Using a series of deletion mutants spanning the hinge region of the protein, we
      observed that amino acid residues 201 through 220 are required for the activity
      of P protein in both replication and transcription. Neither insertion nor
      deletion had any effect on the interaction of P protein with N or L proteins.
      Infectious VSVs with a deletion in the hinge region possessed retarded growth
      characteristics and exhibited small-plaque morphology. Interestingly, VSV
      containing one P protein deletion mutant (PDelta7, with amino acids 141 through
      200 deleted), which possessed significant levels of replication and transcription
      activity, could be amplified only by passage in cells expressing the wild-type P
      protein. We conclude that the hypervariable hinge region of the P protein plays
      an important role in viral RNA synthesis. Furthermore, our results provide a
      previously unidentified function for the P protein: it plays a critical role in
      the assembly of infectious VSV.

PMID- 15956556
TI  - Novel nuclear export signal-interacting protein, NESI, critical for the assembly
      of hepatitis delta virus.
AB  - The process of host factor-mediated nucleocytoplasmic transport is critical for
      diverse cellular events in eukaryotes and the life cycle of viruses. We have
      previously identified a chromosome region maintenance 1-independent nuclear
      export signal (NES) at the C terminus of the large form of hepatitis delta
      antigen (HDAg), designated NES(HDAg-L) that is required for the assembly of
      hepatitis delta virus (HDV) (C.-H. Lee et al., J. Biol. Chem. 276:8142-8148,
      2001). To look for interacting proteins of the NES(HDAg-L), yeast two-hybrid
      screening was applied using the GAL4-binding domain fused to the NES(HDAg-L) as
      bait. Among the positive clones, one encodes a protein, designated NESI [NES(HDAg
      L) interacting protein] that specifically interacted with the wild-type NES(HDAg
      L) but not with the export/package-defective HDAg-L mutant, NES*(HDAg-L), in
      which Pro-205 has been replaced by Ala. Northern blot analysis revealed NESI as
      the gene product of a 1.9-kb endogenous mRNA transcript that is present
      predominantly in human liver tissue. NESI consists of 467 amino acid residues and
      bears a putative actin-binding site and a bipartite nuclear localization signal.
      Specific interaction between HDAg-L and NESI was further confirmed by
      coimmunoprecipitation and immunofluorescence staining. Overexpression of
      antisense NESI RNAs inhibited the expression of NESI and abolished HDAg-L
      mediated nuclear export and assembly of HDV genomic RNA. These data indicate a
      critical role of NESI in the assembly of HDV through interaction with HDAg-L.

PMID- 15956557
TI  - Longitudinal assessment of human immunodeficiency virus type 1 (HIV-1)-specific
      gamma interferon responses during the first year of life in HIV-1-infected
      infants.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection results in different
      patterns of viral replication in pediatric compared to adult populations. The
      role of early HIV-1-specific responses in viral control has not been well
      defined, because most studies of HIV-1-infected infants have been retrospective
      or cross-sectional. We evaluated the association between HIV-1-specific gamma
      interferon (IFN-gamma) release from the cells of infants of 1 to 3 months of age
      and peak viral loads and mortality in the first year of life among 61 Kenyan HIV
      1-infected infants. At 1 month, responses were detected in 7/12 (58%) and 6/21
      (29%) of infants infected in utero and peripartum, respectively (P = 0.09), and
      in approximately 50% of infants thereafter. Peaks of HIV-specific spot-forming
      units (SFU) increased significantly with age in all infants, from 251/10(6)
      peripheral blood mononuclear cells (PBMC) at 1 month of age to 501/10(6) PBMC at
      12 months of age (P = 0.03), although when limited to infants who survived to 1
      year, the increase in peak HIV-specific SFU was no longer significant (P = 0.18).
      Over the first year of life, infants with IFN-gamma responses at 1 month had peak
      plasma viral loads, rates of decline of viral load, and mortality risk similar to
      those of infants who lacked responses at 1 month. The strength and breadth of IFN
      gamma responses at 1 month were not significantly associated with viral
      containment or mortality. These results suggest that, in contrast to HIV-1
      infected adults, in whom strong cytotoxic T lymphocyte responses in primary
      infection are associated with reductions in viremia, HIV-1-infected neonates
      generate HIV-1-specific CD8+-T-cell responses early in life that are not clearly
      associated with improved clinical outcomes.

PMID- 15956558
TI  - Effect of CD8+ lymphocyte depletion on virus containment after simian
      immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239delta3
      vaccinated rhesus macaques.
AB  - Although live attenuated vaccines can provide potent protection against simian
      immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges,
      the specific immune responses that confer this protection have not been
      determined. To test whether cellular immune responses mediated by CD8+
      lymphocytes contribute to this vaccine-induced protection, we depleted rhesus
      macaques vaccinated with the live attenuated virus SIVmac239Delta3 of CD8+
      lymphocytes and then challenged them with SIVmac251 by the intravenous route.
      While vaccination did not prevent infection with the pathogenic challenge virus,
      the postchallenge levels of virus in the plasmas of vaccinated control animals
      were significantly lower than those for unvaccinated animals. The depletion of
      CD8+ lymphocytes at the time of challenge resulted in virus levels in the plasma
      that were intermediate between those of the vaccinated and unvaccinated controls,
      suggesting that CD8+ cell-mediated immune responses contributed to protection.
      Interestingly, at the time of challenge, animals expressing the Mamu-A*01 major
      histocompatibility complex class I allele showed significantly higher frequencies
      of SIV-specific CD8+ T-cell responses and lower neutralizing antibody titers than
      those in Mamu-A*01- animals. Consistent with these findings, the depletion of
      CD8+ lymphocytes abrogated vaccine-induced protection, as judged by the peak
      postchallenge viremia, to a greater extent in Mamu-A*01+ than in Mamu-A*01-
      animals. The partial control of postchallenge viremia after CD8+ lymphocyte
      depletion suggests that both humoral and cellular immune responses induced by
      live attenuated SIV vaccines can contribute to protection against a pathogenic
      challenge and that the relative contribution of each of these responses to
      protection may be genetically determined.

PMID- 15956559
TI  - Preliminary physical mapping of RNA-RNA linkages in the genomic RNA of Moloney
      murine leukemia virus.
AB  - Retrovirus particles contain two copies of their genomic RNA, held together in a
      dimer by linkages which presumably consist of a limited number of base pairs. In
      an effort to localize these linkages, we digested deproteinized RNA from Moloney
      murine leukemia virus (MLV) particles with RNase H in the presence of
      oligodeoxynucleotides complementary to specific sites in viral RNA. The cleaved
      RNAs were then characterized by nondenaturing gel electrophoresis. We found that
      fragments composed of nucleotides 1 to 754 were dimeric, with a linkage as
      thermostable as that between dimers of intact genomic RNA. In contrast, there was
      no stable linkage between fragments consisting of nucleotides 755 to 8332. Thus,
      the most stable linkage between monomers is on the 5' side of nucleotide 754.
      This conclusion is in agreement with earlier electron microscopic analyses of
      partially denatured viral RNAs and with our study (C. S. Hibbert, J. Mirro, and
      A. Rein, J. Virol. 78:10927-10938, 2004) of encapsidated nonviral mRNAs
      containing inserts of viral sequence. We obtained similar results with RNAs from
      immature MLV particles, in which the dimeric linkage is different from that in
      mature particles and has not previously been localized. The 5' and 3' fragments
      of cleaved RNA are all held together by thermolabile linkages, indicating the
      presence of tethering interactions between bases 5' and bases 3' of the cleavage
      site. When RNAs from mature particles were cleaved at nucleotide 1201, we
      detected tethering interactions spanning the cleavage site which are
      intramonomeric and are as strong as the most stable linkage between the monomers.

PMID- 15956560
TI  - Promoters, transcripts, and regulatory proteins of Mungbean yellow mosaic
      geminivirus.
AB  - Geminiviruses package circular single-stranded DNA and replicate in the nucleus
      via a double-stranded intermediate. This intermediate also serves as a template
      for bidirectional transcription by polymerase II. Here, we map promoters and
      transcripts and characterize regulatory proteins of Mungbean yellow mosaic virus
      Vigna (MYMV), a bipartite geminivirus in the genus Begomovirus. The following new
      features, which might also apply to other begomoviruses, were revealed in MYMV.
      The leftward and rightward promoters on DNA-B share the transcription activator
      AC2-responsive region, which does not overlap the common region that is nearly
      identical in the two DNA components. The transcription unit for BC1 (movement
      protein) includes a conserved, leader-based intron. Besides negative-feedback
      regulation of its own leftward promoter on DNA-A, the replication protein AC1, in
      cooperation with AC2, synergistically transactivates the rightward promoter,
      which drives a dicistronic transcription unit for the coat protein AV1. AC2 and
      the replication enhancer AC3 are expressed from one dicistronic transcript driven
      by a strong promoter mapped within the upstream AC1 gene. Early and constitutive
      expression of AC2 is consistent with its essential dual function as an activator
      of viral transcription and a suppressor of silencing.

PMID- 15956561
TI  - Isolation of a bovine plasma fibronectin-containing complex which inhibits the
      expression of bovine leukemia virus p24.
AB  - Bovine leukemia virus (BLV) is a deltaretrovirus that infects cattle worldwide.
      In agriculturally intensive regions, approximately 30% of dairy cows are BLV
      infected. Like the human T-cell leukemia virus (HTLV), there is a lengthy period
      of viral quiescence after initial infection with BLV. Unlike HTLV, BLV resides
      predominantly in B cells. Lymphoma is observed in less than 10% of BLV-infected
      adult cattle. Although viremia is undetectable in vivo, BLV-infected peripheral
      blood mononuclear cells readily become productive when cultured in vitro.
      Productivity is markedly diminished when cultures are supplemented with bovine
      plasma. This inhibitory activity of bovine plasma has been attributed to the
      "plasma blocking factor" (PBF). Here, we describe the purification of a PBF whose
      activity was resistant to heating to 65 degrees C for 10 min and was attributable
      to a fibronectin-containing complex of approximately 320 kDa under nonreducing
      conditions. By use of two-dimensional polyacrylamide gel electrophoresis and
      matrix-assisted laser desorption ionization-time of flight (mass spectrometry), a
      protein with a size of 220 kDa and a pI of 5.4 was identified as a member of the
      fibronectin group of molecules. Both the purified protein and the commercially
      available bovine fibronectin inhibited BLV production in naturally infected
      peripheral blood mononuclear cells, although the fibronectin was less
      biologically active.

PMID- 15956562
TI  - Limited sequence evolution within persistently targeted CD8 epitopes in chronic
      human immunodeficiency virus type 1 infection.
AB  - Studies in acute human immunodeficiency virus type 1 (HIV-1) infection indicate
      viral evolution under CD8 T-cell immune selection pressure, but the effects of
      ongoing immune pressure on epitope evolution during chronic infection are not
      well described. In this study, we performed a detailed longitudinal analysis of
      viral sequence variation within persistently targeted cytotoxic T-lymphocyte
      (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent
      viremia. Responses were quantitated using freshly isolated peripheral blood
      lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma)
      Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in
      each person. In the majority of cases, the dominant epitope sequence did not
      change over time, even in the presence of responses of sufficient magnitude that
      they were detectable using fresh peripheral blood mononuclear cells in direct
      lytic assays. Only 4 of the 14 autologous epitopes tested represented potential
      CTL escape variants; however, in most cases strong responses to these epitopes
      persisted for the 6 years of study. Although persistent IFN-gamma responses were
      detected to all epitopes, direct lytic assays demonstrated declining responses to
      some epitopes despite the persistence of the targeted sequence in vivo. These
      data indicate limited viral evolution within persistently targeted CD8 T-cell
      epitopes during the chronic phase of infection and suggest that these regions of
      the virus are either refractory to sequence change or that persistently activated
      CD8 T-cell responses in chronic infection exert little functional selection
      pressure.

PMID- 15956563
TI  - Development of a novel system to study hepatitis delta virus genome replication.
AB  - Hepatitis delta virus (HDV) genome replication requires the virus-encoded small
      delta protein (deltaAg). During replication, nucleotide sequence changes
      accumulate on the HDV RNA, leading to the translation of deltaAg species that are
      nonfunctional or even inhibitory. A replication system was devised where all
      deltaAg was conditionally provided from a separate and unchanging source. A line
      of human embryonic kidney cells was stably transfected with a single copy of cDNA
      encoding small deltaAg, with expression under tetracycline (TET) control. Next,
      HDV genome replication was initiated in these cells by transfection with a
      mutated RNA unable to express deltaAg. Thus, replication of this RNA was under
      control of the TET-inducible deltaAg. In the absence of TET, there was sufficient
      deltaAg to allow a low level of HDV replication that could be maintained for at
      least 1 year. When TET was added, both deltaAg and genomic RNA increased
      dramatically within 2 days. With clones of such cells, designated 293-HDV, the
      burst of HDV RNA replication interfered with cell cycling. Within 2 days, there
      was a fivefold enhancement of G1/G0 cells relative to both S and G2/M cells, and
      by 6 days, there was extensive cell detachment and death. These findings and
      those of other studies that are under way demonstrate the potential applications
      of this experimental system.

PMID- 15956564
TI  - Enhanced potency of plasmid DNA microparticle human immunodeficiency virus
      vaccines in rhesus macaques by using a priming-boosting regimen with recombinant
      proteins.
AB  - DNA vaccines have been used widely in experimental primate models of human
      immunodeficiency virus (HIV), but their effectiveness has been limited. In this
      study, we evaluated three technologies for increasing the potency of DNA vaccines
      in rhesus macaques. These included DNA encoding Sindbis virus RNA replicons
      (pSINCP), cationic poly(lactide-co-glycolide) (PLG) microparticles for DNA
      delivery, and recombinant protein boosting. The DNA-based pSINCP replicon
      vaccines encoding HIV Gag and Env were approximately equal in potency to human
      cytomegalovirus (CMV) promoter-driven conventional DNA vaccines (pCMV). The PLG
      microparticle DNA delivery system was particularly effective at enhancing
      antibody responses induced by both pCMV and pSINCP vaccines and had less effect
      on T cells. Recombinant Gag and Env protein boosting elicited rapid and strong
      recall responses, in some cases to levels exceeding those seen after DNA or
      DNA/PLG priming. Of note, Env protein boosting induced serum-neutralizing
      antibodies and increased frequencies of gamma interferon-producing CD4 T cells
      severalfold. Thus, PLG microparticles are an effective means of delivering DNA
      vaccines in nonhuman primates, as demonstrated for two different types of DNA
      vaccines encoding two different antigens, and are compatible for use with DNA
      prime-protein boost regimens.

PMID- 15956565
TI  - Differential sensitivity of murine leukemia virus to APOBEC3-mediated inhibition
      is governed by virion exclusion.
AB  - While members of the APOBEC3 family of human intrinsic resistance factors are
      able to restrict the replication of Vif-deficient forms of human immunodeficiency
      virus type 1 (HIV-1), they are unable to block replication of wild-type HIV-1 due
      to the action of Vif, which induces their degradation. In contrast, HIV-1 Vif is
      unable to block inhibition mediated by APOBEC3 proteins expressed by several
      heterologous species, including mice. Here, we have asked whether the simple
      retrovirus murine leukemia virus (MLV) is sensitive to restriction by the cognate
      murine or heterologous, human APOBEC3 proteins. We demonstrate that MLV is highly
      sensitive to inhibition by human APOBEC3G and APOBEC3B but resistant to
      inhibition by murine APOBEC3 or by other human APOBEC3 proteins, including
      APOBEC3F. This sensitivity fully correlates with the ability of these proteins to
      be packaged into MLV virion particles: i.e., human APOBEC3G and APOBEC3B are
      packaged while murine APOBEC3 and human APOBEC3F are excluded. Moreover, this
      packaging in turn correlates with the differential ability of these APOBEC3
      proteins to bind MLV Gag. Together, these data suggest that MLV Gag has evolved
      to avoid binding, and hence virion packaging, of the cognate murine APOBEC3
      protein but that MLV infectivity is still restricted by certain heterologous
      APOBEC3 proteins that retain this ability. Moreover, these results suggest that
      APOBEC3 proteins may help prevent the zoonotic infection of humans by simple
      retroviruses and provide a mechanism for how simple retroviruses can avoid
      inhibition by APOBEC3 family members.

PMID- 15956566
TI  - Recombinant human immunodeficiency virus type 1 integrase exhibits a capacity for
      full-site integration in vitro that is comparable to that of purified
      preintegration complexes from virus-infected cells.
AB  - Retrovirus preintegration complexes (PIC) in virus-infected cells contain the
      linear viral DNA genome (approximately 10 kbp), viral proteins including
      integrase (IN), and cellular proteins. After transport of the PIC into the
      nucleus, IN catalyzes the concerted insertion of the two viral DNA ends into the
      host chromosome. This successful insertion process is termed "full-site
      integration." Reconstitution of nucleoprotein complexes using recombinant human
      immunodeficiency virus type 1 (HIV-1) IN and model viral DNA donor substrates
      (approximately 0.30 to 0.48 kbp in length) that are capable of catalyzing
      efficient full-site integration has proven difficult. Many of the products are
      half-site integration reactions where either IN inserts only one end of the viral
      donor substrate into a circular DNA target or into other donors. In this report,
      we have purified recombinant HIV-1 IN at pH 6.8 in the presence of MgSO4 that
      performed full-site integration nearly as efficiently as HIV-1 PIC. The size of
      the viral DNA substrate was significantly increased to 4.1 kbp, thus allowing for
      the number of viral DNA ends and the concentrations of IN in the reaction
      mixtures to be decreased by a factor of approximately 10. In a typical reaction
      at 37 degrees C, recombinant HIV-1 IN at 5 to 10 nM incorporated 30 to 40% of the
      input DNA donor into full-site integration products. The synthesis of full-site
      products continued up to approximately 2 h, comparable to incubation times used
      with HIV-1 PIC. Approximately 5% of the input donor was incorporated into the
      circular target producing half-site products with no significant quantities of
      other integration products produced. DNA sequence analysis of the viral DNA
      target junctions derived from wild-type U3 and U5 coupled reactions showed an
      approximately 70% fidelity for the HIV-1 5-bp host site duplications. Recombinant
      HIV-1 IN successfully utilized a mutant U5 end containing additional nucleotide
      extensions for full-site integration demonstrating that IN worked properly under
      nonideal active substrate conditions. The fidelity of the 5-bp host site
      duplications was also high with these coupled mutant U5 and wild-type U3 donor
      ends. These studies suggest that recombinant HIV-1 IN is at least as capable as
      native IN in virus particles and approaching that observed with HIV-1 PIC for
      catalyzing full-site integration.

PMID- 15956567
TI  - An interplay between hypervariable region 1 of the hepatitis C virus E2
      glycoprotein, the scavenger receptor BI, and high-density lipoprotein promotes
      both enhancement of infection and protection against neutralizing antibodies.
AB  - Hepatitis C virus (HCV) circulates in the bloodstream in different forms,
      including complexes with immunoglobulins and/or lipoproteins. To address the
      significance of such associations, we produced or treated HCV pseudoparticles
      (HCVpp), a valid model of HCV cell entry and its inhibition, with naive or
      patient-derived sera. We demonstrate that infection of hepatocarcinoma cells by
      HCVpp is increased more than 10-fold by human serum factors, of which high
      density lipoprotein (HDL) is a major component. Infection enhancement requires
      scavenger receptor BI, a molecule known to mediate HDL uptake into cells as well
      as HCVpp entry, and involves conserved amino acid positions in hypervariable
      region 1 (HVR1) of the E2 glycoprotein. Additionally, we show that the
      interaction with human serum or HDL, but not with low-density lipoprotein, leads
      to the protection of HCVpp from neutralizing antibodies, including monoclonal
      antibodies and antibodies present in patient sera. Finally, the deletion or
      mutation of HVR1 in HCVpp abolishes infection enhancement and leads to increased
      sensitivity to neutralizing antibodies/sera compared to that of parental HCVpp.
      Altogether, these results assign to HVR1 new roles which are complementary in
      helping HCV to survive within its host. Besides immune escape by mutation, HRV1
      can mediate the enhancement of cell entry and the protection of virions from
      neutralizing antibodies. By preserving a balance between these functions, HVR1
      may be essential for the viral persistence of HCV.

PMID- 15956568
TI  - New DNA viruses identified in patients with acute viral infection syndrome.
AB  - A sequence-independent PCR amplification method was used to identify viral
      nucleic acids in the plasma samples of 25 individuals presenting with symptoms of
      acute viral infection following high-risk behavior for human immunodeficiency
      virus type 1 transmission. GB virus C/hepatitis G virus was identified in three
      individuals and hepatitis B virus in one individual. Three previously undescribed
      DNA viruses were also detected, a parvovirus and two viruses related to TT virus
      (TTV). Nucleic acids in human plasma that were distantly related to bacterial
      sequences or with no detectable similarities to known sequences were also found.
      Nearly complete viral genome sequencing and phylogenetic analysis confirmed the
      presence of a new parvovirus distinct from known human and animal parvoviruses
      and of two related TTV-like viruses highly divergent from both the TTV and TTV
      like minivirus groups. The detection of two previously undescribed viral species
      in a small group of individuals presenting acute viral syndrome with unknown
      etiology indicates that a rich yield of new human viruses may be readily
      identifiable using simple methods of sequence-independent nucleic acid
      amplification and limited sequencing.

PMID- 15956569
TI  - Lentivirus-specific cytotoxic T-lymphocyte responses are rapidly lost in
      thymectomized cats infected with feline immunodeficiency virus.
AB  - To what extent the thymus is needed to preserve the virus-specific cytotoxic T
      lymphocyte (CTL) response of lentivirus-infected adults is unclear. Presented
      here is the first definitive study using thymectomized (ThX) animals to directly
      evaluate the contribution of thymic function to lentivirus-specific CTL response
      and the control of lentivirus infections. ThX and mock-ThX cats were inoculated
      with feline immunodeficiency virus (FIV) and monitored for their FIV-specific CTL
      responses. Early in infection, both FIV-ThX and FIV-mock-ThX cats produced
      similar CTL responses, but surprisingly, after 20 weeks, the FIV-ThX cats showed
      a statistically significant loss of FIV-specific CTL activity, while FIV-infected
      cats with intact thymuses continued to maintain FIV-specific CTL. The loss of CTL
      did not affect plasma virus load, which remained elevated for both groups. These
      results emphasize the importance of thymic integrity in maintaining immunity to
      lentiviruses, but also bring into question the notion that virus load is
      regulated predominantly by the virus-specific CTL response.

PMID- 15956570
TI  - Avian sarcoma and leukosis virus cytopathic effect in the absence of TVB death
      domain signaling.
AB  - The cytopathic effect (CPE) seen with some subgroups of avian sarcoma and
      leukosis virus (ASLV) is associated with viral Env activation of the death
      promoting activity of TVB (a tumor necrosis factor receptor-related receptor that
      is most closely related to mammalian TNF-related apoptosis-inducing ligand
      [TRAIL] receptors) and with viral superinfection leading to unintegrated viral
      DNA (UVD) accumulation, which is presumed to activate a cellular DNA damage
      response. In this study, we employed cells that express signaling-deficient ASLV
      receptors to demonstrate that an ASLV CPE can be uncoupled from the death
      promoting functions of the TVB receptor. However, these cell-killing events were
      associated with much higher levels of viral superinfection and DNA accumulation
      than those seen when the virus used signaling-competent TVB receptors. These
      findings suggest that a putative cellular DNA damage response that is activated
      by UVD accumulation might act in concert with the death-signaling pathways
      activated by Env-TVB interactions to trigger cell death. Such a model is
      consistent with the well-established synergy that exists between TRAIL-signaling
      pathways and DNA damage responses which is currently being exploited in cancer
      therapy regimens.

PMID- 15956571
TI  - In-depth, longitudinal analysis of viral quasispecies from an individual triply
      infected with late-stage human immunodeficiency virus type 1, using a multiple
      PCR primer approach.
AB  - Co-infections with more than one human immunodeficiency virus type 1 (HIV-1)
      subtype appear to be the source of new recombinant strains and may be commonplace
      in high-risk cohorts exposed to multiple subtypes. Many potential dual infections
      have been identified during the HIV Superinfection Study in Mbeya, Tanzania,
      where 600 female bar workers who are highly exposed to subtypes A, C, and D have
      been evaluated every 3 months for over 3 years by use of the MHAacd HIV-1
      genotyping assay. Here we describe an in-depth, longitudinal analysis of the
      viral quasispecies in a woman who was triply infected with HIV-1 and who
      developed AIDS and passed away 15 months after enrollment. The MHA results
      obtained at 0, 3, 6, 9, and 12 months revealed dual-probe reactivities and shifts
      in subtype over time, indicating a potential dual infection and prompting further
      investigation. The multiple infection was confirmed by PCR amplification of three
      genome regions by a multiple primer approach, followed by molecular cloning and
      sequencing. A highly complex viral quasispecies was found, including several
      recombinant forms, with vpu/gp120 being the most diverse region. A significant
      fluctuation in molecular forms over time was observed, showing that the serial
      sample format is highly desirable, if not essential, for the identification of
      multiple infections. In a separate experiment, we confirmed that the detection of
      co-infections is more efficient with the use of multiple amplification primers to
      overcome the primer bias that results from the enormous diversity in the HIV-1
      genome.

PMID- 15956572
TI  - Characterization of a previously unidentified viral protein in porcine circovirus
      type 2-infected cells and its role in virus-induced apoptosis.
AB  - Porcine circovirus type 2 (PCV2) is the causative agent of postweaning
      multisystemic wasting syndrome in pigs. In this study, transcription and
      translation of a novel viral gene (termed ORF3 here) was detected during
      productive infection of PCV2 in PK15 cells. The results of infection with ORF3
      deficient PCV2 by site-directed mutagenesis indicated that the protein is not
      essential for viral replication. To investigate the underlying mechanism of cell
      death caused by replication of PCV2, apoptosis characterized by chromosomal
      condensation and fragmentation, formation of apoptotic bodies, and significant
      increase in hypodiploids were detected in infected cells. We further demonstrated
      that PCV2-induced apoptosis required the activation of caspase-8 but not caspase
      9. The activation of caspase-8 results in the activation of caspase-3 as shown by
      an increase in the cleavage of the caspase substrate in the infected cells. To
      determine whether ORF3 protein could trigger apoptosis, ORF3 as well as ORF1 and
      ORF2 genes were transiently expressed in PK15 and Cos-7 cells for apoptotic
      activity assay. Transfection of cells with the ORF3 alone induced apoptosis using
      a pathway similar to that described in the context of viral infection. This is
      further confirmed by a significant decrease in apoptotic activity of infected
      cells in the absence of the ORF3 expression, suggesting that the protein plays a
      major role in the induction of virus-induced apoptosis. Altogether, these results
      indicate that ORF3 is a novel PCV2 protein that is not essential for viral
      replication in cultured cells but is involved in PCV2-induced apoptosis by
      activating caspase-8 and caspase-3 pathways.

PMID- 15956573
TI  - Torovirus non-discontinuous transcription: mutational analysis of a subgenomic
      mRNA promoter.
AB  - Toroviruses (order Nidovirales) are enveloped positive-strand RNA viruses of
      mammals. The prototype torovirus, equine torovirus strain Berne (Berne virus
      [BEV]), uses two different transcription strategies to produce a 3'-coterminal
      nested set of subgenomic (sg) mRNAs. Its mRNA 2 carries a leader sequence derived
      from the 5' end of the genome and is produced via discontinuous transcription.
      The remaining three sg mRNAs, 3 to 5, are colinear with the 3' end of the genome
      and are made via non-discontinuous RNA synthesis. Their synthesis is supposedly
      regulated by short conserved sequence motifs, 5'-ACN3-4CUUUAGA-3', within the
      noncoding intergenic regions that precede the M, HE, and N genes (A. L. van
      Vliet, S. L. Smits, P. J. Rottier, and R. J. de Groot, EMBO J. 21:6571-6580,
      2002). We have now studied the--for nidoviruses unusual--non-discontinuous
      transcription mechanism in further detail by probing the role of the postulated
      transcription-regulating sequences (TRSs). To this end, we constructed a
      synthetic defective interfering (DI) RNA, carrying a 24-nucleotide segment of the
      intergenic region between the HE and N genes. We demonstrate that this DI RNA,
      when introduced into BEV-infected cells, directs the synthesis of a sg DI RNA
      species; in fact, a 16-nucleotide cassette containing the TRS already proved
      sufficient. Synthesis of this sg DI RNA, like that of mRNAs 3 to 5 of the
      standard virus, initiated at the 5'-most adenylate of the TRS. An extensive
      mutational analysis of the TRS is presented. Our results provide first and formal
      experimental evidence that the conserved motifs within the BEV intergenic
      sequences indeed drive sg RNA synthesis.

PMID- 15956574
TI  - Seroprevalence and genomic divergence of circulating strains of feline
      immunodeficiency virus among Felidae and Hyaenidae species.
AB  - Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline
      species and is closely related to human immunodeficiency virus (HIV) and simian
      immunodeficiency virus (SIV). Species-specific strains of FIV have been described
      for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo),
      leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a
      three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens)
      and PCR analysis to survey worldwide prevalence, distribution, and genomic
      differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae
      species. Although FIV infects a wide variety of host species, it is confirmed to
      be endemic in free-ranging populations of nine Felidae and one Hyaenidae species.
      These include the large African carnivores (lion, leopard, cheetah, and spotted
      hyena), where FIV is widely distributed in multiple populations; most of the
      South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and
      tigrina), which maintain a lower FIV-positive level throughout their range; and
      two Asian species, the Pallas' cat, which has a species-specific strain of FIV,
      and the leopard cat, which has a domestic cat FIV strain in one population.
      Phylogenetic analysis of FIV proviral sequence demonstrates that most species for
      which FIV is endemic harbor monophyletic, genetically distinct species-specific
      FIV strains, suggesting that FIV transfer between cat species has occurred in the
      past but is quite infrequent today.

PMID- 15956575
TI  - Innate STAT1-dependent genomic response of neurons to the antiviral cytokine
      alpha interferon.
AB  - Alpha/beta interferons (IFNs-alpha/beta) are cytokines that play an essential
      role in the host defense against viral infection. Our previous studies have shown
      that the key IFN signaling molecule STAT1 is highly elevated and activated in
      central nervous system neurons during viral infection and in transgenic mice with
      astrocyte production of IFN-alpha (glial fibrillary acidic protein [GFAP]-IFN
      alpha), suggesting that neurons are a very responsive target cell population for
      IFNs. To elucidate the genomic response of neurons to IFN-alpha, we undertook
      studies both in vitro and in vivo. Gene chip analysis was applied to RNA from IFN
      alpha-treated or untreated primary cortical neuronal cultures derived from
      embryonic day 15 fetal wild-type or STAT1 knockout (KO) mice. The expression of
      51 known and 5 unknown genes was increased significantly by more than twofold
      after exposure of wild-type but not STAT1 KO neurons to IFN-alpha. Some more
      highly expressed genes included IFN-induced 15-kDa protein, ubiquitin-specific
      protease 18, glucocorticoid attenuated response genes, IFN-induced GTPases, and
      the chemokine CXCL10. For several of these genes, the gene chip findings were
      confirmed by RNase protection assays. In addition, examination of the expression
      of some of these selected genes revealed that they were increased in neurons in
      the brain of either GFAP-IFN-alpha mice or mice infected with lymphocytic
      choriomeningitis virus. In conclusion, our study revealed a robust STAT1
      dependent genomic response of neurons to IFN-alpha, highlighting an innate
      potential of these cells to defend against viral infection in the brain.

PMID- 15956577
TI  - Characterization of hortulanus endogenous murine leukemia virus, an endogenous
      provirus that encodes an infectious murine leukemia virus of a novel subgroup.
AB  - Simple retroviruses present a unique opportunity for examining the host-virus
      relationship. Following exogenous infection and integration into the germ line,
      copies of these viruses can become fixed within the genome. The resulting
      endogenous proviral "fossils" represent a record of past retroviral infections
      and forms. Previous work in our laboratory has been directed at dissecting the
      extensive nonecotropic murine leukemia virus content of the mouse genome. One
      such provirus, hortulanus endogenous murine leukemia virus (HEMV), found in a
      single copy in the genome of Mus spicilegus, was remarkable for characteristics
      that suggested that it was ancient and related to the hypothetical common
      ancestor of murine leukemia viruses (MLVs) and other gammaretroviral species. In
      the present study, we have analyzed its functional properties. Transfection of a
      molecular clone of the HEMV provirus into mouse-derived cell lines revealed that
      it is replication competent. Furthermore, host range and interference studies
      revealed a strictly ecotropic host range and the use of a receptor distinct from
      those used by other classical MLVs. The identity of nucleotide sequence of the
      long terminal repeats (LTRs) further suggested that HEMV is a relatively recent
      insertion into the M. spicilegus genome at the distal end of chromosome 7.
      Although unique to M. spicilegus, its presence in a homozygous state in three
      individuals obtained from different regions implies that it has been present long
      enough to become fixed in this species. Exhaustive phylogenetic analysis of all
      regions of the HEMV genome supported the previously assigned ancestral position
      of HEMV relative to other MLV-related viruses. Thus, HEMV is a relatively recent
      introduction into the Mus germ line but is representative of a relatively
      ancestral MLV group.

PMID- 15956576
TI  - Control of translation by the 5'- and 3'-terminal regions of the dengue virus
      genome.
AB  - The genomic RNAs of flaviviruses such as dengue virus (DEN) have a 5' m7GpppN cap
      like those of cellular mRNAs but lack a 3' poly(A) tail. We have studied the
      contributions to translational expression of 5'- and 3'-terminal regions of the
      DEN serotype 2 genome by using luciferase reporter mRNAs transfected into Vero
      cells. DCLD RNA contained the entire DEN 5' and 3' untranslated regions (UTRs),
      as well as the first 36 codons of the capsid coding region fused to the
      luciferase reporter gene. Capped DCLD RNA was as efficiently translated in Vero
      cells as capped GLGpA RNA, a reporter with UTRs from the highly expressed alpha
      globin mRNA and a 72-residue poly(A) tail. Analogous reporter RNAs with
      regulatory sequences from West Nile and Sindbis viruses were also strongly
      expressed. Although capped DCLD RNA was expressed much more efficiently than its
      uncapped form, uncapped DCLD RNA was translated 6 to 12 times more efficiently
      than uncapped RNAs with UTRs from globin mRNA. The 5' cap and DEN 3' UTR were the
      main sources of the translational efficiency of DCLD RNA, and they acted
      synergistically in enhancing translation. The DEN 3' UTR increased mRNA
      stability, although this effect was considerably weaker than the enhancement of
      translational efficiency. The DEN 3' UTR thus has translational regulatory
      properties similar to those of a poly(A) tail. Its translation-enhancing effect
      was observed for RNAs with globin or DEN 5' sequences, indicating no codependency
      between viral 5' and 3' sequences. Deletion studies showed that translational
      enhancement provided by the DEN 3' UTR is attributable to the cumulative
      contributions of several conserved elements, as well as a nonconserved domain
      adjacent to the stop codon. One of the conserved elements was the conserved
      sequence (CS) CS1 that is complementary to cCS1 present in the 5' end of the DEN
      polyprotein open reading frame. Complementarity between CS1 and cCS1 was not
      required for efficient translation.

PMID- 15956578
TI  - Paracrine inhibition of prion propagation by anti-PrP single-chain Fv
      miniantibodies.
AB  - Prion diseases are characterized by the deposition of PrP(Sc), an abnormal form
      of the cellular prion protein PrP(C). A growing body of evidence suggests that
      antibodies to PrP(C) can antagonize deposition of PrP(Sc). However, host
      tolerance hampers the induction of immune responses to PrP(C), and cross-linking
      of PrP(C) by bivalent anti-PrP antibodies is neurotoxic. In order to obviate
      these problems, we explored the antiprion potential of recombinant single-chain
      antibody (scFv) fragments. scFv fragments derived from monoclonal anti-PrP
      antibody 6H4, flagged with c-myc and His6 tags, were correctly processed and
      secreted by mammalian RD-4 rhabdomyosarcoma cells. When cocultured with cells
      secreting anti-PrP scFv, chronically prion-infected neuroblastoma cells ceased to
      produce PrP(Sc), even if antibody-producing cells were physically separated from
      target cells in transwell cultures. Expression of scFv with irrelevant
      specificity, or of similarly tagged molecules, was not curative. Therefore,
      eukaryotically expressed scFv exerts a paracrine antiprion activity. The effector
      functions encoded by immunoglobulin constant domains are unnecessary for this
      effect. Because of their small size and their monovalent binding, scFv fragments
      may represent candidates for gene transfer-based immunotherapy of prion diseases.

PMID- 15956579
TI  - Envelope protein glycosylation status influences mouse neuroinvasion phenotype of
      genetic lineage 1 West Nile virus strains.
AB  - The introduction of West Nile virus (WNV) into North America has been associated
      with relatively high rates of neurological disease and death in humans, birds,
      horses, and some other animals. Previous studies identified strains in both
      genetic lineage 1 and genetic lineage 2, including North American isolates of
      lineage 1, that were highly virulent in a mouse neuroinvasion model, while other
      strains were avirulent or significantly attenuated (D. W. C. Beasley, L. Li, M.
      T. Suderman, and A. D. T. Barrett, Virology 296:17-23, 2002). To begin to
      elucidate the basis for these differences, we compared a highly virulent New York
      1999 (NY99) isolate with a related Old World lineage 1 strain, An4766 (ETH76a),
      which is attenuated for mouse neuroinvasion. Genomic sequencing of ETH76a
      revealed a relatively small number of nucleotide (5.1%) and amino acid (0.6%)
      differences compared with NY99. These differences were located throughout the
      genome and included five amino acid differences in the envelope protein gene.
      Substitution of premembrane and envelope genes of ETH76a into a NY99 infectious
      clone backbone yielded a virus with altered in vitro growth characteristics and a
      mouse virulence phenotype comparable to ETH76a. Further site-specific mutagenesis
      studies revealed that the altered phenotype was primarily mediated via loss of
      envelope protein glycosylation and that this was associated with altered
      stability of the virion at mildly acidic pH. Therefore, the enhanced virulence of
      North American WNV strains compared with other Old World lineage 1 strains is at
      least partly mediated by envelope protein glycosylation.

PMID- 15956580
TI  - Herpes simplex virus ICP27 activation of stress kinases JNK and p38.
AB  - We previously reported that herpes simplex virus type 1 (HSV-1) can activate the
      stress-activated protein kinases (SAPKs) p38 and JNK. In the present study, we
      undertook a comprehensive and comparative analysis of the requirements for viral
      protein synthesis in the activation of JNK and p38. Infection with the UL36
      mutant tsB7 or with UV-irradiated virus indicated that both JNK and p38
      activation required viral gene expression. Cycloheximide reversal or
      phosphonoacetic acid treatment of wild-type virus-infected cells as well as
      infection with the ICP4 mutant vi13 indicated that only the immediate-early class
      of viral proteins were required for SAPK activation. Infection with ICP4, ICP27,
      or ICP0 mutant viruses indicated that only ICP27 was necessary. Additionally, we
      determined that in the context of virus infection ICP27 was sufficient for SAPK
      activation and activation of the p38 targets Mnk1 and MK2 by infecting with
      mutants deleted for various combinations of immediate-early proteins.
      Specifically, the d100 (0-/4-) and d103 (4-/22-/47-) mutants activated p38 and
      JNK, while the d106 (4-/22-/27-/47-) and d107 (4-/27-) mutants did not. Finally,
      infections with a series of ICP27 mutants demonstrated that the functional domain
      of ICP27 required for activation was located in the region encompassing amino
      acids 20 to 65 near the N terminus of the protein and that the C-terminal
      transactivation activity of ICP27 was not necessary.

PMID- 15956581
TI  - Human cytomegalovirus UL130 protein promotes endothelial cell infection through a
      producer cell modification of the virion.
AB  - Human cytomegalovirus (HCMV) growth in endothelial cells (EC) requires the
      expression of the UL131A-128 locus proteins. In this study, the UL130 protein
      (pUL130), the product of the largest gene of the locus, is shown to be a luminal
      glycoprotein that is inefficiently secreted from infected cells but is
      incorporated into the virion envelope as a Golgi-matured form. To investigate the
      mechanism of the UL130-mediated promotion of viral growth in EC, we performed a
      complementation analysis of a UL130 mutant strain. To provide UL130 in trans to
      viral infections, we constructed human embryonic lung fibroblast (HELF) and human
      umbilical vein endothelial cell (HUVEC) derivative cell lines that express UL130
      via a retroviral vector. When the UL130-negative virus was grown in UL130
      complementing HELF, the infectivity of progeny virions for HUVEC was restored to
      the wild-type level. In contrast, the infectivity of the UL130-negative virus for
      UL130-complementing HUVEC was low and similar to that of the same virus infecting
      control noncomplementing HUVEC. The UL130-negative virus, regardless of whether
      or not it had been complemented in the prior cycle, could form plaques only on
      UL130-complementing HUVEC, not control HUVEC. Because (i) both wild-type and
      UL130-transcomplemented virions maintained their infectivity for HUVEC after
      purification, (ii) UL130 failed to complement in trans the UL130-negative virus
      when it was synthesized in a cell separate from the one that produced the
      virions, and (iii) pUL130 is a virion protein, models are favored in which pUL130
      acquisition in the producer cell renders HCMV virions competent for a subsequent
      infection of EC.

PMID- 15956582
TI  - Wild-type-like viral replication potential of human immunodeficiency virus type 1
      envelope mutants lacking palmitoylation signals.
AB  - Palmitoylation of the cytoplasmic domain of the human immunodeficiency type virus
      type 1 (HIV-1) envelope (Env) transmembrane protein, gp41, has been implicated in
      Env targeting to detergent-resistant lipid rafts, Env incorporation into the
      virus, and viral infectivity. In contrast, we provide evidence here to show that
      HIV-1 infectivity, Env targeting to lipid rafts, and Env incorporation into the
      virus are independent of cytoplasmic tail palmitoylation. The T-cell (T)-tropic
      HXB2-based virus, which utilizes CXCR4 as the entry coreceptor, carrying a Cys-to
      Ser mutation at residue 764 or 837 or at both replicated with wild-type (WT)
      virus replication kinetics in CD4+ T cells. The properties of Env expression,
      precursor processing, cell surface expression, and Env incorporation of these
      three mutant viruses were normal compared to those of the WT virus. These three
      mutant Env proteins all effectively mediated one-cycle virus infection. When the
      Cys residues were replaced by Ala residues, all single and double mutants still
      retained the phenotypes of infectivity, Env incorporation, and lipid raft
      localization of the WT Env. When Cys-to-Ala substitutions were introduced into
      the macrophage (M)-tropic ConB virus, which utilizes CCR5 as the coreceptor,
      these mutations did not affect the replication potential, Env phenotypes, lipid
      raft targeting, or Env assembly into the virus of the WT Env. These T- and M
      tropic mutants also productively replicated in human primary CD4+ T cells.
      Moreover, mutations at both Cys residues significantly reduced the level of
      palmitoylation of the Env. Our results together support the notion that
      palmitoylation of the cytoplasmic tail of the HIV-1 Env is not essential for the
      HIV-1 virus life cycle.

PMID- 15956583
TI  - Flavivirus activates phosphatidylinositol 3-kinase signaling to block caspase
      dependent apoptotic cell death at the early stage of virus infection.
AB  - Flaviviruses such as dengue virus (DEN) and Japanese encephalitis virus (JEV) are
      medically important in humans. The lipid kinase, phosphatidylinositol 3-kinase
      (PI3K) and its downstream target Akt have been implicated in the regulation of
      diverse cellular functions such as proliferation, and apoptosis. Since JEV and
      DEN appear to trigger apoptosis in cultured cells at a rather late stage of
      infection, we evaluated the possible roles of the PI3K/Akt signaling pathway in
      flavivirus-infected cells. We found that Akt phosphorylation was noticeable in
      the JEV- and DEN serotype 2 (DEN-2)-infected neuronal N18 cells in an early,
      transient, PI3K- and lipid raft-dependent manner. Blocking of PI3K activation by
      its specific inhibitor LY294002 or wortmannin greatly enhanced virus-induced
      cytopathic effects (CPEs), even at an early stage of infection, but had no effect
      on virus production. This severe CPE was characterized as apoptotic cell death as
      evidenced by TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin
      nick end labeling) staining and cleavage of caspase-3 and poly(ADP-ribose)
      polymerase (PARP). Mechanically, the initiator and effector caspases involved are
      mainly caspase-9 and caspase-6, since only a pan-caspase inhibitor and the
      inhibitors preferentially target caspase-9 and -6, but not the ones antagonizing
      caspase-8, -3, or -7 alleviated the levels of PARP cleavage after virus infection
      and PI3K blockage. Furthermore, Bcl-2 appears to be a crucial mediator downstream
      of PI3K/Akt signaling, since overexpression of Bcl-2 reduced virus-induced
      apoptosis even when PI3K activation was repressed. Collectively, our results
      suggest an anti-apoptotic role for the PI3K/Akt pathway triggered by JEV and DEN
      2 to protect infected cells from early apoptotic cell death.

PMID- 15956584
TI  - Role of N-linked glycans in the functions of hepatitis C virus envelope
      glycoproteins.
AB  - Hepatitis C virus (HCV) encodes two viral envelope glycoproteins. E1 contains 4
      or 5 N-linked glycosylation sites and E2 contains up to 11, with most of the
      sites being well conserved, suggesting that they play an essential role in some
      functions of these proteins. For this study, we used retroviral pseudotyped
      particles harboring mutated HCV envelope glycoproteins to study these glycans.
      The mutants were named with an N followed by a number related to the relative
      position of the potential glycosylation site in each glycoprotein (E1N1 to E1N4
      for E1 mutants and E2N1 to E2N11 for E2 mutants). The characterization of these
      mutants allowed us to define three phenotypes. For the first group (E1N3, E2N3,
      E2N5, E2N6, E2N7, and E2N9), the infectivities of the mutants were close to that
      of the wild type. The second group (E1N1, E1N2, E1N4, E2N1, and E2N11) contained
      mutants that were still infectious but whose infectivities were reduced to <50%
      that of the wild type. The third group (E2N2, E2N4, E2N8, and E2N10) contained
      mutants that had almost totally lost infectivity. The absence of infectivity of
      the E2N8 and E2N10 mutants was due to the lack of incorporation of the E1E2
      heterodimer into HCVpp, which was due to misfolding of the heterodimer, as shown
      by immunoprecipitation with conformation-sensitive antibodies and by a CD81 pull
      down assay. The absence of infectivity of the E2N2 and E2N4 mutants indicated
      that these two glycans are involved in controlling HCV entry. Altogether, the
      data indicate that some glycans of HCV envelope glycoproteins play a major role
      in protein folding and others play a role in HCV entry.

PMID- 15956585
TI  - Mobilization and mechanism of transcription of integrated self-inactivating
      lentiviral vectors.
AB  - Permanent genetic modification of replicating primitive hematopoietic cells by an
      integrated vector has many potential therapeutic applications. Both
      oncoretroviral and lentiviral vectors have a predilection for integration into
      transcriptionally active genes, creating the potential for promoter activation or
      gene disruption. The use of self-inactivating (SIN) vectors in which a deletion
      of the enhancer and promoter sequences from the 3' long terminal repeat (LTR) is
      copied over into the 5' LTR during vector integration is designed to improve
      safety by reducing the risk of mobilization of the vector genome and the
      influence of the LTR on nearby cellular promoters. Our results indicate that SIN
      vectors are mobilized in cells expressing lentiviral proteins, with the frequency
      of mobilization influenced by features of the vector design. The mechanism of
      transcription of integrated vector genomes was evaluated using a promoter trap
      design with a vector encoding tat but lacking an upstream promoter in a cell line
      in which drug resistance depended on tat expression. In six clones studied, all
      transcripts originated from cryptic promoters either upstream or within the
      vector genome. We estimate that approximately 1 in 3,000 integrated vector
      genomes is transcribed, leading to the inference that activation of cryptic
      promoters must depend on local features of chromatin structure and the
      constellation of nearby regulatory elements as well as the nature of the
      regulatory elements within the vector.

PMID- 15956586
TI  - A functional histidine-tagged replication initiator protein: implications for the
      study of single-stranded DNA virus replication in planta.
AB  - Replication initiation of nanoviruses, plant viruses with a multipartite circular
      single-stranded DNA genome, is triggered by the master Rep (M-Rep) protein. To
      enable the study of interactions between M-Rep and viral or host factors involved
      in replication, we designed oligohistidine-tagged variants of the nanovirus Faba
      bean necrotic yellows virus (FBNYV) M-Rep protein that allow affinity
      purification of enzymatically active M-Rep from plant tissue. The tagged M-Rep
      protein was able to initiate replication of its cognate and other FBNYV DNAs in
      Nicotiana benthamiana leaf disks and plants. The replicon encoding the tagged M
      Rep protein multiplied and moved systemically in FBNYV-infected Vicia faba plants
      and was transmitted by the aphid vector of the virus. Using the tagged M-Rep
      protein, we demonstrated the in planta interaction between wild-type M-Rep and
      its tagged counterpart. Such a tagged and fully functional replication initiator
      protein will have bearings on the isolation of protein complexes from plants.

PMID- 15956587
TI  - Attenuation of equine influenza viruses through truncations of the NS1 protein.
AB  - Equine influenza is a common disease of the horse, causing significant morbidity
      worldwide. Here we describe the establishment of a plasmid-based reverse genetics
      system for equine influenza virus. Utilizing this system, we generated three
      mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have
      previously shown that a recombinant human influenza virus lacking the NS1 gene
      (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting
      that the NS1 protein is responsible for IFN antagonist activity. Contrary to
      previous findings with human influenza virus, we found that in the case of equine
      influenza virus, the length of the NS1 protein did not correlate with the level
      of attenuation of that virus. With equine influenza virus, the mutant virus with
      the shortest NS1 protein turned out to be the least attenuated. We speculate that
      the basis for attenuation of the equine NS1 mutant viruses generated is related
      to their level of NS1 protein expression. Our findings show that the recombinant
      mutant viruses are impaired in their ability to inhibit IFN production in vitro
      and they do not replicate as efficiently as the parental recombinant strain in
      embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore,
      these attenuated mutant NS1 viruses may have potential as candidates for a live
      equine influenza vaccine.

PMID- 15956589
TI  - Virus isolates during acute and chronic human immunodeficiency virus type 1
      infection show distinct patterns of sensitivity to entry inhibitors.
AB  - We studied the effect of entry inhibitors on 58 virus isolates derived during
      acute and chronic infection to validate these inhibitors in vitro and to probe
      whether viruses at early and chronic disease stages exhibit general differences
      in the interaction with entry receptors. We included members of all types of
      inhibitors currently identified: (i) agents that block gp120 binding to CD4 (CD4
      IgG2 and monoclonal antibody [MAb] IgG1b12), (ii) compounds that block the
      interaction with CCR5 (the chemokine RANTES/CCL5, the small-molecule inhibitor
      AD101, and the anti-CCR5 antibody PRO 140), (iii) the fusion inhibitor
      enfuvirtide (T-20), and (iv) neutralizing antibodies directed against gp120 (MAb
      2G12) and gp41 (MAbs 2F5 and 4E10). No differences between viruses from acute and
      chronic infections in the susceptibility to inhibitors targeting the CD4 binding
      site, CCR5, or fusion or to MAb 2G12 were apparent, rendering treatment with
      entry inhibitors feasible across disease stages. The notable exceptions were
      antibodies 2F5 and 4E10, which were more potent in inhibiting viruses from acute
      infection (P = 0.0088 and 0.0005, respectively), although epitopes of these MAbs
      were equally well preserved in both groups. Activities of these MAbs correlated
      significantly with each other, suggesting that common features of the viral
      envelope modulate their potencies.

PMID- 15956590
TI  - Herpes simplex virus 1 ICP22 regulates the accumulation of a shorter mRNA and of
      a truncated US3 protein kinase that exhibits altered functions.
AB  - The U(S)3 open reading frame of herpes simplex virus 1 (HSV-1) was reported to
      encode two mRNAs each directing the synthesis of the same protein. We report that
      the U(S)3 gene encodes two proteins. The predominant U(S)3 protein is made in
      wild-type HSV-1-infected cells. The truncated mRNA and a truncated protein
      designated U(S)3.5 and initiating from methionine 77 were preeminent in cells
      infected with a mutant lacking the gene encoding ICP22. Both the wild-type and
      truncated proteins also accumulated in cells transduced with a baculovirus
      carrying the entire U(S)3 open reading frame. The U(S)3.5 protein accumulating in
      cells infected with the mutant lacking the gene encoding ICP22 mediated the
      phosphorylation of histone deacetylase 1, a function of U(S)3 protein, but failed
      to block apoptosis of the infected cells. The U(S)3.5 and U(S)3 proteins differ
      with respect to the range of functions they exhibit.

PMID- 15956588
TI  - Molecular interactions of human immunodeficiency virus type 1 with primary human
      oral keratinocytes.
AB  - Infection of the oral mucosa of human immunodeficiency virus type 1 (HIV-1)
      infected individuals remains an under-evaluated and somewhat enigmatic process.
      Nonetheless, it is of profound importance in the ongoing AIDS pandemic, based on
      its potential as a site of person-to-person transmission of the virus as well as
      a location of HIV-1 pathogenesis and potential reservoir of disease in the
      setting of virally suppressive highly active antiretroviral therapy. We utilized
      molecular and virological techniques to analyze HIV-1 infection of primary human
      mucosal cells and also evaluated the proapoptotic potential of selected HIV-1
      proteins in primary isolated human oral keratinocytes. Primary isolated human
      oral keratinocytes were plated on 0.4 microM polyethylenetetraphthalate cell
      culture inserts to form an in vitro oral mucosal layer. The strength of this
      layer in forming a barrier was determined by measuring trans-epithelial
      electrical current passage across the monolayer. The oral keratinocyte monolayers
      had trans-epithelial electrical resistance of approximately 176 to 208 omega. For
      viral infectivity assays, the macrophage-tropic (R5) HIV-1 strains, YU-2 and ADA,
      and T-cell-line-tropic (X4), NL4-3 virions, incubated with or without
      deoxynucleoside triphosphates (dNTPs) and/or the polyamines spermine and
      spermidine, were used to infect oral keratinocytes. Of importance, polyamines and
      dNTPs have been shown to enhance natural endogenous reverse transcription (NERT),
      a step essential for early lentiviral infection, and are abundantly present in
      human semen. The infectivities of HIV-1 strains YU-2, ADA, and NL4-3 for these
      primary keratinocytes were dramatically increased by the addition of
      physiological concentrations of dNTPs, spermine, and spermidine. Binding and
      viral internalization assay studies showed no differences in these oral mucosal
      cells, with or without NERT-altering agents. It was also observed that the
      recombinant, cell-free HIV-1 proteins Nef, Tat, and gp120 (R5) induced apoptosis
      in primary oral keratinocytes compared with the results seen with nontreated
      cells or cells treated with glutathione S-transferase protein as a control under
      similar conditions. Microarray analyses suggested that HIV-1 gp120 and Tat induce
      apoptosis in primary human oral keratinocytes via the Fas/FasL apoptotic pathway,
      whereas induction of apoptosis by Nef occurs through both Fas/FasL and
      mitochondrial apoptotic pathways. Thus, these findings suggest molecular
      mechanisms by which semen in particular, as well as other bodily fluids such as
      cervicovaginal secretions, could increase oral transmission of HIV-1 via
      increasing infectivity in confluent and low-replicating oral keratinocytes. As
      well, the induction of apoptosis in human oral keratinocytes with relevant HIV-1
      specific proteins suggests another potential complementary mechanism by which the
      oral mucosa barrier may be disrupted during HIV-1 infection in vivo.

PMID- 15956591
TI  - DNA vaccines expressing different forms of simian immunodeficiency virus antigens
      decrease viremia upon SIVmac251 challenge.
AB  - We have tested the efficacy of DNA immunization as a single vaccination modality
      for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further
      improve immunogenicity of the native proteins, we generated expression vectors
      producing fusion of the proteins Gag and Env to the secreted chemokine MCP3,
      targeting the viral proteins to the secretory pathway and to a beta-catenin
      (CATE) peptide, targeting the viral proteins to the intracellular degradation
      pathway. Macaques immunized with vectors expressing the MCP3-tagged fusion
      proteins developed stronger antibody responses. Following mucosal challenge with
      pathogenic SIVmac251, the vaccinated animals showed a statistically significant
      decrease in viral load (P = 0.010). Interestingly, macaques immunized with a
      combination of vectors expressing three forms of antigens (native protein and
      MCP3 and CATE fusion proteins) showed the strongest decrease in viral load (P =
      0.0059). Postchallenge enzyme-linked immunospot values for Gag and Env as well as
      gag-specific T-helper responses correlated with control of viremia. Our data show
      that the combinations of DNA vaccines producing native and modified forms of
      antigens elicit more balanced immune responses able to significantly reduce
      viremia for a long period (8 months) following pathogenic challenge with
      SIVmac251.

PMID- 15956592
TI  - Activation of the Kaposi's sarcoma-associated herpesvirus major latency locus by
      the lytic switch protein RTA (ORF50).
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) maintains a latent infection in
      primary effusion lymphoma cells but can be induced to enter full lytic
      replication by exposure to a variety of chemical inducing agents or by expression
      of the KSHV-encoded replication and transcription activator (RTA) protein. During
      latency, only a few viral genes are expressed, and these include the three genes
      of the so-called latency transcript (LT) cluster: v-FLIP (open reading frame 71
      [ORF71]), v-cyclin (ORF72), and latency-associated nuclear antigen (ORF73).
      During latency, all three open reading frames are transcribed from a common
      promoter as part of a multicistronic mRNA. Subsequent alternative mRNA splicing
      and internal ribosome entry allows for the expression of each protein. Here, we
      show that transcription of LT cassette mRNA can be induced by RTA through the
      activation of a second promoter (LT(i)) immediately downstream of the
      constitutively active promoter (LT(c)). We identified a minimal cis-regulatory
      region, which overlaps with the promoter for the bicistronic K14/v-GPCR delayed
      early gene that is transcribed in the opposite direction. In addition to a TATA
      box at -30 relative to the LT(i) mRNA start sites, we identified three separate
      RTA response elements that are also utilized by the K14/v-GPCR promoter.
      Interestingly, LT(i) is unresponsive to sodium butyrate, a potent inducer of
      lytic replication. This suggests there is a previously unrecognized class of RTA
      responsive promoters that respond to direct, but not indirect, induction of RTA.
      These studies highlight the fact that induction method can influence the precise
      program of viral gene expression during early events in reactivation and also
      suggest a mechanism by which RTA contributes to establishment of latency during
      de novo infections.

PMID- 15956593
TI  - Analysis of foot-and-mouth disease virus internalization events in cultured
      cells.
AB  - It has been demonstrated that foot-and-mouth disease virus (FMDV) can utilize at
      least four members of the alpha(V) subgroup of the integrin family of receptors
      in vitro. The virus interacts with these receptors via a highly conserved
      arginine-glycine-aspartic acid amino acid sequence motif located within the betaG
      betaH loop of VP1. While there have been extensive studies of virus-receptor
      interactions at the cell surface, our understanding of the events during viral
      entry into the infected cell is still not clear. We have utilized confocal
      microscopy to analyze the entry of two FMDV serotypes (types A and O) after
      interaction with integrin receptors at the cell surface. In cell cultures
      expressing both the alphaVbeta3 and alphaVbeta6 integrins, virus adsorbed to the
      cells at 4 degrees C appears to colocalize almost exclusively with the
      alphaVbeta6 integrin. Upon shifting the infected cells to 37 degrees C, FMDV
      capsid proteins were detected within 15 min after the temperature shift, in
      association with the integrin in vesicular structures that were positive for a
      marker of clathrin-mediated endocytosis. In contrast, virus did not colocalize
      with a marker for caveola-mediated endocytosis. Virus remained associated with
      the integrin until about 1 h after the temperature shift, when viral proteins
      appeared around the perinuclear region of the cell. By 15 min after the
      temperature shift, viral proteins were seen colocalizing with a marker for early
      endosomes, while no colocalization with late endosomal markers was observed. In
      the presence of monensin, which raises the pH of endocytic vesicles and has been
      shown to inhibit FMDV replication, viral proteins were not released from the
      recycling endosome structures. Viral proteins were not observed associated with
      the endoplasmic reticulum or the Golgi. These data indicate that FMDV utilizes
      the clathrin-mediated endocytosis pathway to infect the cells and that viral
      replication begins due to acidification of endocytic vesicles, causing the
      breakdown of the viral capsid structure and release of the genome by an as-yet
      unidentified mechanism.

PMID- 15956595
TI  - Histidine at residue 99 and the transmembrane region of the precursor membrane
      prM protein are important for the prM-E heterodimeric complex formation of
      Japanese encephalitis virus.
AB  - The formation of the flavivirus prM-E complex is an important step for the
      biogenesis of immature virions, which is followed by a subsequent cleavage of prM
      to M protein through cellular protease to result in the production and release of
      mature virions. In this study, the intracellular formation of the prM-E complex
      of Japanese encephalitis virus was investigated by baculovirus coexpression of
      prM and E in trans in Sf9 insect cells as analyzed by anti-E antibody
      immunoprecipitation and sucrose gradient sedimentation analysis. A series of
      carboxyl-terminally truncated prM mutant baculoviruses was constructed to
      demonstrate that the truncations of the transmembrane (TM) region resulted in a
      reduction of the formation of the stable prM-E complex by approximately 40% for
      the TM1 (at residues 130 to 147 [prM130-147]) truncation and 20% for TM2 (at
      prM153-167) truncation. Alanine-scanning site-directed mutagenesis on the prM99
      103 region indicated that the His99 residue was the critical prM binding element
      for stable prM-E heterodimeric complex formation. The single amino acid mutation
      at the His99 residue of prM abolishing the prM-E interaction was not due to
      reduced expression or different subcellular location of the mutant prM protein
      involved in prM-E interactions as characterized by pulse-chase labeling and
      confocal scanning microscopic analysis. Recombinant subviral particles were
      detected in the Sf9 cell culture supernatants by baculovirus coexpression of prM
      and E proteins but not with the prM H99A mutant. Sequence alignment analysis was
      further conducted with different groups of flaviviruses to show that the prM H99
      residues are generally conserved. Our findings are the first report to
      characterize the minimum binding elements of the prM protein that are involved in
      prM-E interactions of flaviviruses. This information, concerning a molecular
      framework for the prM protein, is considered to elucidate the structure/function
      relationship of the prM-E complex synthesis and provide the proper trajectory for
      flavivirus assembly and maturation.

PMID- 15956594
TI  - Early events in integrin alphavbeta6-mediated cell entry of foot-and-mouth
      disease virus.
AB  - We have shown that foot-and-mouth disease virus (FMDV) infection mediated by the
      integrin alphavbeta6 takes place through clathrin-dependent endocytosis but not
      caveolae or other endocytic pathways that depend on lipid rafts. Inhibition of
      clathrin-dependent endocytosis by sucrose treatment or expression of a dominant
      negative version of AP180 inhibited virus entry and infection. Similarly,
      inhibition of endosomal acidification inhibited an early step in infection.
      Blocking endosomal acidification did not interfere with surface expression of
      alphavbeta6, virus binding to the cells, uptake of the virus into endosomes, or
      cytoplasmic virus replication, suggesting that the low pH within endosomes is a
      prerequisite for delivery of viral RNA into the cytosol. Using immunofluorescence
      confocal microscopy, FMDV colocalized with alphavbeta6 at the cell surface but
      not with the B subunit of cholera toxin, a marker for lipid rafts. At 37 degrees
      C, virus was rapidly taken up into the cells and colocalized with markers for
      early and recycling endosomes but not with a marker for lysosomes, suggesting
      that infection occurs from within the early or recycling endosomal compartments.
      This conclusion was supported by the observation that FMDV infection is not
      inhibited by nocodazole, a reagent that inhibits vesicular trafficking between
      early and late endosomes (and hence trafficking to lysosomes). The integrin
      alphavbeta6 was also seen to accumulate in early and recycling endosomes on virus
      entry, suggesting that the integrin serves not only as an attachment receptor but
      also to deliver the virus to the acidic endosomes. These findings are all
      consistent with FMDV infection proceeding via clathrin-dependent endocytosis.

PMID- 15956596
TI  - Perforin and Fas cytolytic pathways coordinately shape the selection and
      diversity of CD8+-T-cell escape variants of influenza virus.
AB  - Antigenic variation is a viral strategy exploited to promote survival in the face
      of the host immune response and represents a major challenge for efficient
      vaccine development. Influenza viruses are pathogens with high transmissibility
      and mutation rates, enabling viral escape from immunity induced by prior
      infection or vaccination. Intense selection from neutralizing antibody drives
      antigenic changes in the surface glycoproteins, resulting in emergence of new
      strains able to reinfect hosts immune to previously circulating viruses. CD8+
      cytotoxic T cells (CTLs) also provide protective immunity from influenza virus
      infection and may contribute to the antigenic evolution of influenza viruses.
      Utilizing mice transgenic for an influenza virus NP366-374 peptide-specific T
      cell receptor, we demonstrated that the respiratory tract is a suitable site for
      generation of escape variants of influenza virus selected by CTL in vivo. In this
      report the contributions of the perforin and Fas pathways utilized by influenza
      virus-specific CTLs in viral clearance and selection of CTL escape variants have
      been evaluated. While transgenic CTLs deficient in either perforin- or Fas
      mediated pathways are efficient in initial pulmonary viral control, variant virus
      emergence was observed in all the mice studied, although the spectrum of viral
      CTL escape variants selected varied profoundly. Thus, a less-restricted
      repertoire of escape variants was observed in mice with an intact perforin
      cytotoxic pathway compared with a limited variant diversity in perforin pathway
      deficient mice, although maximal variant diversity was observed in mice having
      both Fas and perforin pathways intact. We conclude that selection of viral CTL
      escape variants reflects coordinate action between the tightly controlled
      perforin/granzyme pathway and the more promiscuous Fas/FasL pathway.

PMID- 15956597
TI  - Characterization of a novel vpu-harboring simian immunodeficiency virus from a
      Dent's Mona monkey (Cercopithecus mona denti).
AB  - We report the identification of a new simian immunodeficiency virus (SIV),
      designated SIVden, in a naturally infected Dent's Mona monkey (Cercopithecus mona
      denti), which was kept as pet in Kinshasa, capital of the Democratic Republic of
      Congo. SIVden is genetically distinct from the previously characterized primate
      lentiviruses. Analysis of the full-length genomic sequence revealed the presence
      of a vpu open reading frame. This gene is also found in the virus lineage of
      human immunodeficiency virus type 1 (HIV-1) and chimpanzee immunodeficiency virus
      (SIVcpz) and was recently described in viruses isolated from Cercopithecus
      nictitans, Cercopithecus mona, and Cercopithecus cephus. The SIVden vpu coding
      region is shorter than the HIV-1/SIVcpz and the SIVgsn, SIVmon, and SIVmus
      counterparts. Unlike Pan troglodytes schweinfurthii viruses (SIVcpzPts) and
      Cercopithecus monkey viruses (SIVgsn, SIVmon, and SIVmus), the SIVden Vpu
      contains the characteristic DSGXES motif which was shown to be involved in Vpu
      mediated CD4 and IkappaBalpha proteolysis in HIV-1 infected cells. Although it
      harbors a vpu gene, SIVden is phylogenetically closer to SIVdeb isolated from De
      Brazza's monkeys (Cercopithecus neglectus), which lacks a vpu gene, than to
      Cercopithecus monkey viruses, which harbor a vpu sequence.

PMID- 15956598
TI  - pH-induced conformational change of the rotavirus VP4 spike: implications for
      cell entry and antibody neutralization.
AB  - The rotavirus spike protein, VP4, is a major determinant of infectivity and
      neutralization. Previously, we have shown that trypsin-enhanced infectivity of
      rotavirus involves a transformation of the VP4 spike from a flexible to a rigid
      bilobed structure. Here we show that at elevated pH the spike undergoes a
      drastic, irreversible conformational change and becomes stunted, with a
      pronounced trilobed appearance. These particles with altered spikes, at a normal
      pH of 7.5, despite the loss of infectivity and the ability to hemagglutinate,
      surprisingly exhibit sialic acid (SA)-independent cell binding in contrast to the
      SA-dependent cell binding exhibited by native virions. Remarkably, a neutralizing
      monoclonal antibody that remains bound to spikes throughout the pH changes (pH 7
      to 11 and back to pH 7) completely prevents this conformational change,
      preserving the SA-dependent cell binding and hemagglutinating functions of the
      virion. A hypothesis that emerges from the present study is that high-pH
      treatment triggers a conformational change that mimics a post-SA-attachment step
      to expose an epitope recognized by a downstream receptor in the rotavirus cell
      entry process. This process involves sequential interactions with multiple
      receptors, and the mechanism by which the antibody neutralizes is by preventing
      this conformational change.

PMID- 15956599
TI  - Initiation and exacerbation of autoimmune demyelination of the central nervous
      system via virus-induced molecular mimicry: implications for the pathogenesis of
      multiple sclerosis.
AB  - Epidemiological studies indicate that infectious agents are important in the
      pathogenesis of multiple sclerosis (MS). Our previous reports showed that the
      infection of SJL mice with a nonpathogenic variant of Theiler's murine
      encephalomyelitis virus (TMEV) engineered to express a naturally occurring
      Haemophilus influenzae-encoded molecular mimic (HI574-586) of an immunodominant
      self-myelin proteolipid protein epitope (PLP139-151) induced a rapid-onset
      demyelinating disease associated with the activation of PLP139-151-specific Th1
      responses. The current results extend our previous findings in four critical
      respects. We show that disease initiation by the H. influenzae mimic is prevented
      by tolerance to the self PLP139-151 epitope, definitively proving the occurrence
      of infection-induced molecular mimicry. We demonstrate that the H. influenzae
      mimic epitope can be processed from the flanking sequences within the native
      mimic protein. We show that the H. influenzae mimic epitope only induces an
      immunopathologic self-reactive Th1 response and subsequent clinical disease in
      the context of the TMEV infection and not when administered in complete Freund's
      adjuvant, indicating that molecular mimicry-induced disease initiation requires
      virus-activated innate immune signals. Lastly, we show that the infection of SJL
      mice with TMEV expressing the H. influenzae mimic can exacerbate a previously
      established nonprogressive autoimmune disease of the central nervous system.
      Collectively, these findings illustrate the evolving mechanisms by which virus
      infections may contribute to both the initiation and exacerbation of autoimmune
      diseases, and they have important implications for MS pathogenesis.

PMID- 15956600
TI  - Identification of paramyxovirus V protein residues essential for STAT protein
      degradation and promotion of virus replication.
AB  - Some paramyxovirus V proteins induce STAT protein degradation, and the amino
      acids essential for this process in the human parainfluenza virus type 2 (hPIV2)
      V protein have been studied. Various recombinant hPIV2s and cell lines
      constitutively expressing various mutant V proteins were generated. We found that
      V proteins with replacement of Cys residues of the Cys cluster were still able to
      bind STATs but were unable to induce their degradation. The hPIV2 V protein binds
      STATs via a W-(X)3-W-(X)9-W Trp motif located just upstream of the Cys cluster.
      Replacements of two or more Trp residues in this motif resulted in a failure to
      form a V/STAT2 complex. We have also identified two Phe residues of the hPIV2 V
      protein that are essential for STAT degradation, namely, Phe207, lying within the
      Cys cluster, and Phe143, in the P/V common region of the protein. Interestingly,
      infection of BHK cells with hPIV2 led to the specific degradation of STAT1 and
      not STAT2. Other evidence for the cell species specificity of hPIV2-induced STAT
      degradation is presented. Finally, a V-minus hPIV2, which can express only the P
      protein from its P gene, was generated and partially characterized. In contrast
      to V-minus viruses of other paramyxovirus genera, this V-minus rubulavirus was
      highly debilitated, and its growth even in Vero cells was very limited. The
      structural rubulavirus V proteins, as expected, are thus clearly important in
      promoting virus growth, independent of their anti-interferon (IFN) activity.
      Interestingly, many of the residues that are essential for anti-IFN activity,
      e.g., the Cys of this cluster and Phe207 within this cluster, as well as the Trp
      of this motif, are also essential for promoting virus growth.

PMID- 15956601
TI  - Attenuation of recombinant yellow fever 17D viruses expressing foreign protein
      epitopes at the surface.
AB  - The yellow fever (YF) 17D vaccine is a live attenuated virus. Three-dimensional
      (3D) homology modeling of the E protein structure from YF 17D virus and its
      comparison with that from tick-borne encephalitis virus revealed that it is
      possible to accommodate inserts of different sizes and amino acid compositions in
      the flavivirus E protein fg loop. This is consistent with the 3D structures of
      both the dimeric and trimeric forms in which the fg loop lies exposed to
      solvents. We demonstrate here that YF 17D viruses bearing foreign humoral (17D/8)
      and T-cell (17D/13) epitopes, which vary in sequence and length, displayed growth
      restriction. It is hypothesized that interference with the dimer-trimer
      transition and with the formation of a ring of such trimers in order to allow
      fusion compromises the capability of the E protein to induce fusion of viral and
      endosomal membranes, and a slower rate of fusion may delay the extent of virus
      production. This would account for the lower levels of replication in cultured
      cells and of viremia in monkeys, as well as for the more attenuated phenotype of
      the recombinant viruses in monkeys. Testing of both recombinant viruses (17D/8
      and 17D/13) for monkey neurovirulence also suggests that insertion at the 17D E
      protein fg loop does not compromise the attenuated phenotype of YF 17D virus,
      further confirming the potential use of this site for the development of new live
      attenuated 17D virus-based vaccines.

PMID- 15956602
TI  - Actin is a component of the compensation mechanism in pseudorabies virus virions
      lacking the major tegument protein VP22.
AB  - Despite being a major component of the pseudorabies virus tegument, VP22 is not
      required for PRV replication, virulence, or neuroinvasion (T. del Rio, H. C.
      Werner, and L. W. Enquist, J. Virol. 76:774-782, 2002). In the absence of VP22,
      tegument assembly compensates in a limited fashion with increased incorporation
      of cellular actin. Infection of epithelial cell lines expressing fluorescent
      actin fusion proteins resulted in the incorporation of filamentous and
      nonfilamentous actin into individual virions that were predominately light,
      noninfectious particles. We conclude that cellular actin is incorporated in the
      tegument of wild-type virions and is part of a compensation mechanism for VP22
      null virions.

PMID- 15956604
TI  - Real-time detection of virus particles and viral protein expression with two
      color nanoparticle probes.
AB  - Respiratory syncytial virus (RSV) mediates serious lower respiratory tract
      illness in infants and young children and is a significant pathogen of the
      elderly and immune compromised. Rapid and sensitive RSV diagnosis is important to
      infection control and efforts to develop antiviral drugs. Current RSV detection
      methods are limited by sensitivity and/or time required for detection. In this
      study, we show that antibody-conjugated nanoparticles rapidly and sensitively
      detect RSV and estimate relative levels of surface protein expression. A major
      development is use of dual-color quantum dots or fluorescence energy transfer
      nanobeads that can be simultaneously excited with a single light source.

PMID- 15956603
TI  - A small interfering RNA targeting coxsackievirus B3 protects permissive HeLa
      cells from viral challenge.
AB  - We examined the ability of small interfering RNAs (siRNAs) to disrupt infection
      by coxsackievirus B3 (CVB3). The incorporation of siRNAs dramatically decreased
      cell death in permissive HeLa cells in parallel with a reduction in viral
      replication. Three of four siRNAs had potent anti-CVB3 activity. The present
      study thus demonstrates that the antiviral effect is due to the downregulation of
      viral replication. In addition, an effective CVB3-specific siRNA had similar
      antiviral effects in other related enteroviruses possessing sequence homology in
      the targeted region. Because the CVB3-specific siRNA is effective against other
      enteroviruses, siRNAs have potential for a universal anti-enterovirus strategy.

PMID- 15956605
TI  - Detection of human immunodeficiency virus type 1 Nef and CD4 physical interaction
      in living human cells by using bioluminescence resonance energy transfer.
AB  - CD4 down-regulation by human immunodeficiency virus type 1 (HIV-1) Nef protein is
      a key function for virus virulence. This activity may be mediated by a direct Nef
      CD4 interaction. We investigated the formation, in situ, of such a complex
      between proteins using bioluminescence resonance energy transfer technology and
      co-immunoprecipitations. Our data clearly demonstrate that Nef and CD4 interact
      in intact human cells. Moreover, our results clearly indicate that the dileucine
      motif of the CD4 cytoplasmic domain, critical for the Nef-induced CD4 down
      regulation, is not implicated in the Nef/CD4 complex formation in the cellular
      context.

PMID- 15956606
TI  - Whole-genome transcription profiling of rhesus monkey rhadinovirus.
AB  - Rhesus monkey rhadinovirus (RRV) and Kaposi's sarcoma-associated herpesvirus
      (KSHV; also called human herpesvirus 8) belong to the gamma-2 grouping of
      herpesviruses. RRV and KSHV share a high degree of sequence similarity, and their
      genomes are organized in a similar fashion. RRV serves as an excellent animal
      model system to study the gamma herpesvirus life cycle both in vitro and in vivo.
      We have developed a high-sensitivity, high-throughput, high-specificity real-time
      quantitative reverse transcriptase-based PCR assay for RRV and have used this
      assay to profile transcription from the whole RRV genome during de novo
      productive infection of rhesus fibroblasts. Using this assay, we demonstrate that
      the genome-wide transcription profile for RRV closely parallels the genome-wide
      transcription profile for KSHV.

PMID- 15956607
TI  - Growth of respiratory syncytial virus in primary epithelial cells from the human
      respiratory tract.
AB  - Respiratory syncytial virus (RSV) is the most important cause of lower
      respiratory tract disease in infants and children. To study RSV replication, we
      have developed an in vitro model of human nasopharyngeal mucosa, human airway
      epithelium (HAE). RSV grows to moderate titers in HAE, though they are
      significantly lower than those in a continuous epithelial cell line, HEp-2. In
      HAE, RSV spreads over time to form focal collections of infected cells causing
      minimal cytopathic effect. Unlike HEp-2 cells, in which wild-type and live
      attenuated vaccine candidate viruses grow equally well, the vaccine candidates
      exhibit growth in HAE that parallels their level of attenuation in children.

PMID- 15956608
TI  - Epstein-Barr virus (EBV) latent membrane protein 2A regulates B-cell receptor
      induced apoptosis and EBV reactivation through tyrosine phosphorylation.
AB  - Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong
      latent infection of B cells. Within the immune system, apoptosis is a central
      mechanism in normal lymphocyte homeostasis both during early lymphocyte
      development and in response to antigenic stimuli. In this study, we found that
      latent membrane protein 2A (LMP2A) inhibited B-cell receptor (BCR)-induced
      apoptosis in Burkitt's lymphoma cell lines. Genistein, a specific inhibitor of
      tyrosine-specific protein kinases, blocked BCR-induced apoptosis and EBV
      reactivation in the cells. These findings indicate that LMP2A blocks BCR-induced
      cell apoptosis and EBV reactivation through the inhibition of activation of
      tyrosine kinases by BCR cross-linking.

PMID- 15956609
TI  - Role of papillomavirus E1 initiator dimerization in DNA replication.
AB  - Viral initiator proteins are polypeptides that form oligomeric complexes on the
      origin of DNA replication (ori). These complexes carry out a multitude of
      functions related to initiation of DNA replication, and although many of these
      functions have been characterized biochemically, little is understood about how
      the complexes are assembled. Here we demonstrate that loss of one particular
      interaction, the dimerization between E1 DNA binding domains, has a severe effect
      on DNA replication in vivo but has surprisingly modest effects on most individual
      biochemical activities in vitro. We conclude that the dimer interaction is
      primarily required for initial recognition of ori.

PMID- 15956610
TI  - Vertical transmission of bovine spongiform encephalopathy prions evaluated in a
      transgenic mouse model.
AB  - In this work we show evidence of mother-to-offspring transmission in a transgenic
      mouse line expressing bovine PrP (boTg) experimentally infected by intracerebral
      administration of bovine spongiform encephalopathy (BSE) prions. PrP(res) was
      detected in brains of newborns from infected mothers only when mating was allowed
      near to the clinical stage of disease, when brain PrP(res) deposition could be
      detected by Western blot analysis. Attempts to detect infectivity in milk after
      intracerebral inoculation in boTg mice were unsuccessful, suggesting the
      involvement of other tissues as carriers of prion dissemination. The results
      shown here prove the ability of BSE prions to spread centrifugally from the
      central nervous system to peripheral tissues and to offspring in a mouse model.
      Also, these results may complement previous epidemiological data supporting the
      occurrence of vertical BSE transmission in cattle.

PMID- 15956613
TI  - Determination of muscle pH and glycolytic flux by magnetic resonance spectroscopy
      in contracting human skeletal muscle may have systematic errors.

PMID- 15956611
TI  - In vitro assembly of PB2 with a PB1-PA dimer supports a new model of assembly of
      influenza A virus polymerase subunits into a functional trimeric complex.
AB  - Influenza virus RNA-dependent RNA polymerase is a heterotrimeric complex of PB1,
      PB2, and PA. We show that the individually expressed PB2 subunit can be assembled
      with the coexpressed PB1-PA dimer in vitro into a transcriptionally active
      complex. Furthermore, we demonstrate that a model viral RNA promoter can bind to
      the PB1-PA dimer prior to assembly with PB2. Our results are consistent with a
      recently proposed model for the sequential assembly of viral RNA polymerase
      complex in which the PB1-PA dimeric complex and the PB2 monomer are transported
      into the nucleus separately and then assembled in the nucleus.

PMID- 15956614
TI  - The cover. Dr Horatio C. Wood.

PMID- 15956615
TI  - A piece of my mind. Informed consent.

PMID- 15956616
TI  - Pain and the brain: researchers focus on tackling pain memories.

PMID- 15956617
TI  - Body as art inspires body of art.

PMID- 15956618
TI  - NHLBI's new head: "unprecedented" chance to advance science to clinic.

PMID- 15956625
TI  - Safety of ximelagatran.

PMID- 15956626
TI  - Cost-effectiveness of ximelagatran for stroke prevention.

PMID- 15956627
TI  - Biotechnology products and university-based science.

PMID- 15956628
TI  - Biotechnology products and university-based science.

PMID- 15956629
TI  - Biotechnology products and university-based science.

PMID- 15956630
TI  - Shear hilarity leading to laugh syncope in a healthy man.

PMID- 15956631
TI  - Mechanical reperfusion in patients with acute myocardial infarction presenting
      more than 12 hours from symptom onset: a randomized controlled trial.
AB  - CONTEXT: No specifically designed studies have addressed the role of primary
      percutaneous coronary intervention in patients with acute ST-segment elevation
      myocardial infarction (STEMI) presenting more than 12 hours after symptom onset.
      Current guidelines do not recommend reperfusion treatment in these patients.
      OBJECTIVE: To assess whether an immediate invasive treatment strategy is
      associated with a reduction of infarct size in patients with acute STEMI,
      presenting between 12 and 48 hours after symptom onset, vs a conventional
      conservative strategy. DESIGN, SETTING, AND PATIENTS: International, multicenter,
      open-label, randomized controlled trial conducted from May 23, 2001, to December
      15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms
      admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom
      onset. INTERVENTIONS: Random assignment to either an invasive strategy (n=182)
      based predominantly on coronary stenting with abciximab or a conventional
      conservative treatment strategy (n=183). MAIN OUTCOME MEASURES: The primary end
      point was final left ventricular infarct size according to single-photon emission
      computed tomography study with technetium Tc 99m sestamibi performed between 5
      and 10 days after randomization in 347 patients (95.1%). Secondary end points
      included composite of death, recurrent MI, or stroke at 30 days. RESULTS: The
      final left ventricular infarct size was significantly smaller in patients
      assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%
      15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%
      27.0%; P<.001). The mean difference in final left ventricular infarct size
      between the invasive and conservative groups was -6.8% (95% confidence interval
      [CI], -10.2% to -3.5%). The secondary end points of death, recurrent MI, or
      stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12
      patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27
      1.62; P = .37). CONCLUSION: An invasive strategy based on coronary stenting with
      adjunctive use of abciximab reduces infarct size in patients with acute STEMI
      without persistent symptoms presenting 12 to 48 hours after symptom onset.

PMID- 15956632
TI  - Effect of orlistat on weight and body composition in obese adolescents: a
      randomized controlled trial.
AB  - CONTEXT: The prevalence of overweight and obesity in children and adolescents is
      increasing rapidly. In this population, behavioral therapy alone has had limited
      success in providing meaningful, sustained weight reduction, and pharmacological
      treatment has not been extensively studied. OBJECTIVE: To determine the efficacy
      and safety of orlistat in weight management of adolescents. DESIGN, SETTING, AND
      PATIENTS: Multicenter, 54-week (August 2000-October 2002), randomized, double
      blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI]
      >or=2 units above the 95th percentile) at 32 centers in the United States and
      Canada. INTERVENTIONS: A 120-mg dose of orlistat (n = 357) or placebo (n = 182) 3
      times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories),
      exercise, and behavioral therapy. MAIN OUTCOME MEASURES: Change in BMI; secondary
      measures included changes in waist and hip circumference, weight loss, lipid
      measurements, and glucose and insulin responses to oral glucose challenge.
      RESULTS: There was a decrease in BMI in both treatment groups up to week 12,
      thereafter stabilizing with orlistat but increasing beyond baseline with placebo.
      At the end of the study, BMI had decreased by 0.55 with orlistat but increased by
      0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of
      participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5%
      and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study
      end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo
      (P<.001). Dual-energy x-ray absorptiometry showed that this difference was
      explained by changes in fat mass. Waist circumference decreased in the orlistat
      group but increased in the placebo group (-1.33 cm vs +0.12 cm; P<.05). Generally
      mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of
      the orlistat group and in 1% to 13% of the placebo group. CONCLUSIONS: In
      combination with diet, exercise, and behavioral modification, orlistat
      statistically significantly improved weight management in obese adolescents
      compared with placebo. The use of orlistat for 1 year in this adolescent
      population did not raise major safety issues although gastrointestinal adverse
      events were more common in the orlistat group.

PMID- 15956633
TI  - Fish oil supplementation and risk of ventricular tachycardia and ventricular
      fibrillation in patients with implantable defibrillators: a randomized controlled
      trial.
AB  - CONTEXT: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have
      shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have
      antiarrhythmic effects. OBJECTIVE: To determine whether omega-3 PUFAs have
      beneficial antiarrhythmic effects in patients with a history of sustained
      ventricular tachycardia (VT) or ventricular fibrillation (VF). DESIGN AND
      SETTING: Randomized, double-blind, placebo-controlled trial performed at 6 US
      medical centers with enrollment from February 1999 until January 2003. PATIENTS:
      Two hundred patients with an implantable cardioverter defibrillator (ICD) and a
      recent episode of sustained VT or VF. INTERVENTION: Patients were randomly
      assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were
      followed up for a median of 718 days (range, 20-828 days). MAIN OUTCOME MEASURES:
      Time to first episode of ICD treatment for VT/VF, changes in red blood cell
      concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and
      predetermined subgroup analyses. RESULTS: Patients randomized to receive fish oil
      had an increase in the mean percentage of omega-3 PUFAs in red blood cell
      membranes from 4.7% to 8.3% (P<.001), with no change observed in patients
      receiving placebo. At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%)
      of patients randomized to receive fish oil had ICD therapy for VT/VF compared
      with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo
      (P = .19). In the subset of 133 patients whose qualifying arrhythmia was VT, 61%
      (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at
      6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients
      in the control group (P = .007). Recurrent VT/VF events were more common in
      patients randomized to receive fish oil (P<.001). CONCLUSION: Among patients with
      a recent episode of sustained ventricular arrhythmia and an ICD, fish oil
      supplementation does not reduce the risk of VT/VF and may be proarrhythmic in
      some patients.

PMID- 15956634
TI  - Apolipoprotein E and progression of chronic kidney disease.
AB  - CONTEXT: Apolipoprotein E (APOE) genetic variation has been implicated in
      diabetic nephropathy with the epsilon2 allele increasing and the epsilon4 allele
      decreasing risk. APOE allelic associations with chronic kidney disease beyond
      diabetic nephropathy are unknown, with no studies reported in high-risk African
      American populations. OBJECTIVE: To quantify the risk of chronic kidney disease
      progression associated with APOE in a population-based study including white,
      African American, diabetic, and nondiabetic individuals. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective follow-up (through January 1, 2003) of Atherosclerosis
      Risk in Communities (ARIC) study participants, including 3859 African American
      and 10,661 white adults aged 45 to 64 years without severe renal dysfunction at
      baseline in 1987-1989, sampled from 4 US communities. MAIN OUTCOME MEASURES:
      Incident chronic kidney disease progression, defined as hospitalization or death
      with kidney disease or increase in serum creatinine level of 0.4 mg/dL (35
      micromol/L) or more above baseline, examined by APOE genotypes and alleles.
      RESULTS: During median follow-up of 14 years, chronic kidney disease progression
      developed in 1060 individuals (incidence per 1000 person-years: 5.5 overall; 8.8
      in African Americans and 4.4 in whites). Adjusting for major chronic kidney
      disease risk factors, epsilon2 moderately increased and epsilon4 decreased risk
      of disease progression (likelihood ratio test, P = .03). Further adjustment for
      low- and high-density lipoprotein cholesterol and triglycerides did not attenuate
      relative risks (RRs) (epsilon2: 1.08 [95% CI, 0.93-1.25] and epsilon4: 0.85 [95%
      CI, 0.75-0.95] compared with epsilon3; likelihood ratio test, P = .008). Epsilon4
      decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]).
      Epsilon2 was associated with a decline in renal function (RR, 1.25 [95% CI, 1.02
      1.53]), though not with events, such as hospitalizations or end-stage renal
      disease. Risks were similar stratified by race, sex, diabetes, and hypertension
      (all P values for interaction >.05). Excess risk of chronic kidney disease in
      African Americans was not explained by APOE alleles. CONCLUSIONS: APOE variation
      predicts chronic kidney disease progression, independent of diabetes, race,
      lipid, and nonlipid risk factors. Our study suggests that nonlipid-mediated
      pathways, such as cellular mechanisms of kidney remodeling, may be involved in
      the association of APOE alleles and progression of chronic kidney disease.

PMID- 15956635
TI  - Do quality improvement organizations improve the quality of hospital care for
      Medicare beneficiaries?
AB  - CONTEXT: Quality improvement organizations (QIOs) are charged with improving the
      quality of medical care for Medicare beneficiaries. OBJECTIVE: To explore whether
      the quality of hospital care for Medicare beneficiaries improves more in
      hospitals that voluntarily participate with Medicare's QIOs compared with
      nonparticipating hospitals. DESIGN, SETTING, AND DATA: Data from 4 QIOs charged
      with improving the quality of care in 5 states (Maryland, Nevada, New York, Utah,
      and Washington) and the District of Columbia were used. Hospitals participate
      with the QIOs on quality improvement on a voluntary basis. A retrospective study
      was conducted comparing improvement in the quality of care of patients in
      hospitals that actively participated with the QIOs vs hospitals that did not. The
      medical records of approximately 750 Medicare beneficiaries per state in each of
      5 clinical areas (atrial fibrillation, acute myocardial infarction, heart
      failure, pneumonia, and stroke) were abstracted at baseline (1998) and follow-up
      (2000-2001). MAIN OUTCOME MEASURE: Fifteen quality indicators associated with
      improved outcomes in the prevention or treatment of the 5 clinical areas were
      used as quality of care measures. These 15 indicators were specifically targeted
      by the QIOs for quality improvement during the study period. RESULTS: Hospitals
      that voluntarily participate with the QIOs are more likely to be larger than
      nonparticipating hospitals (P<.05). At baseline, there were statistically
      significant (P<.05) differences between participating and nonparticipating
      hospitals on 5 of 15 quality indicators, with participating hospitals performing
      better on 3 of 5. There was no statistically significant difference in change
      from baseline to follow-up between participating and nonparticipating hospitals
      on 14 of 15 quality indicators. The one exception was that participating
      hospitals improved more on the pneumonia immunization indicator than
      nonparticipating hospitals (P = .005). CONCLUSION: Hospitals that participate
      with the QIO program are not more likely to show improvement on quality
      indicators than hospitals that do not participate.

PMID- 15956636
TI  - Routine vs selective invasive strategies in patients with acute coronary
      syndromes: a collaborative meta-analysis of randomized trials.
AB  - CONTEXT: Patients with unstable angina or non-ST-segment elevation myocardial
      infarction (NSTEMI) can be cared for with a routine invasive strategy involving
      coronary angiography and revascularization or more conservatively with a
      selective invasive strategy in which only those with recurrent or inducible
      ischemia are referred for acute intervention. OBJECTIVE: To conduct a meta
      analysis that compares benefits and risks of routine invasive vs selective
      invasive strategies. DATA SOURCES: Randomized controlled trials identified
      through search of MEDLINE and the Cochrane databases (1970 through June 2004) and
      hand searching of cross-references from original articles and reviews. STUDY
      SELECTION: Trials were included that involved patients with unstable angina or
      NSTEMI who received a routine invasive or a selective invasive strategy. DATA
      EXTRACTION: Major outcomes of death and myocardial infarction (MI) occurring from
      initial hospitalization to the end of follow-up were extracted from published
      results of eligible trials. DATA SYNTHESIS: A total of 7 trials (N = 9212
      patients) were eligible. Overall, death or MI was reduced from 663 (14.4%) of
      4604 patients in the selective invasive group to 561 (12.2%) of 4608 patients in
      the routine invasive group (odds ratio [OR], 0.82; 95% confidence interval [CI],
      0.72-0.93; P = .001). There was a nonsignificant trend toward fewer deaths (6.0%
      vs 5.5%; OR, 0.92; 95% CI, 0.77-1.09; P = .33) and a significant reduction in MI
      alone (9.4% vs 7.3%; OR, 0.75; 95% CI, 0.65-0.88; P<.001). Higher-risk patients
      with elevated cardiac biomarker levels at baseline benefited more from routine
      intervention, with no significant benefit observed in lower-risk patients with
      negative baseline marker levels. During the initial hospitalization, a routine
      invasive strategy was associated with a significantly higher early mortality
      (1.1% vs 1.8% for selective vs routine, respectively; OR, 1.60; 95% CI, 1.14
      2.25; P = .007) and the composite of death or MI (3.8% vs 5.2%; OR, 1.36; 95% CI,
      1.12-1.66; P = .002). But after discharge, the routine invasive strategy was
      associated with fewer subsequent deaths (4.9% vs 3.8%; OR, 0.76; 95% CI, 0.62
      0.94; P = .01) and the composite of death or MI (11.0% vs 7.4%; OR, 0.64; 95% CI,
      0.56-0.75; P<.001). At the end of follow-up, there was a 33% reduction in severe
      angina (14.0% vs 11.2%; OR, 0.77; 95% CI, 0.68-0.87; P<.001) and a 34% reduction
      in rehospitalization (41.3% vs 32.5%; OR, 0.66; 95% CI, 0.60-0.72; P<.001) with a
      routine invasive strategy. CONCLUSIONS: A routine invasive strategy exceeded a
      selective invasive strategy in reducing MI, severe angina, and rehospitalization
      over a mean follow-up of 17 months. But routine intervention was associated with
      a higher early mortality hazard and a trend toward a mortality reduction at
      follow-up. Future strategies should explore ways to minimize the early hazard and
      enhance later benefits by focusing on higher-risk patients and optimizing timing
      of intervention and use of proven therapies.

PMID- 15956637
TI  - Malignant hyperthermia: update on susceptibility testing.
AB  - Malignant hyperthermia (MH) is a pharmacogenetic clinical syndrome that manifests
      as a hypermetabolic crisis when a susceptible individual is exposed to an
      anesthetic triggering agent. Clinical signs include unexplained elevation of end
      tidal carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea,
      hyperthermia, and evidence of rhabdomyolysis. This process is a result of an
      abnormally increased release of calcium from the sarcoplasmic reticulum, which is
      often caused by an inherited mutation in the gene for the ryanodine receptor
      (RYR1) that resides in the membrane of the sarcoplasmic reticulum. The gold
      standard for determination of MH susceptibility is the caffeine-halothane
      contracture test. However, it is invasive, requiring skeletal muscle biopsy and
      is not widely available. Researchers have begun to map mutations within the
      ryanodine receptor gene (chromosome 19q13.1) responsible for conferring MH
      susceptibility. Ryanodine receptor mutations are found in at least 25% of known
      MH susceptible individuals in North America. Mutation analysis has recently
      become available in the United States and is expected to play an integral role in
      the diagnosis of MH susceptibility in the future.

PMID- 15956638
TI  - Acute PCI for ST-segment elevation myocardial infarction: is later better than
      never?

PMID- 15956639
TI  - Pharmacotherapy for adolescent obesity: a weighty issue.

PMID- 15956640
TI  - To cath or not to cath: that is no longer the question.

PMID- 15956641
TI  - JAMA patient page. Malignant hyperthermia.

PMID- 15956642
TI  - Development and validation of therapeutically relevant multi-gene biomarker
      classifiers.

PMID- 15956643
TI  - Erlotinib in gliomas: should selection be based on EGFR and Akt analyses?

PMID- 15956644
TI  - Trastuzumab trials steal show at ASCO meeting.

PMID- 15956645
TI  - FDA attempting to overcome major roadblocks in monitoring drug safety.

PMID- 15956646
TI  - Divide and conquer: new generation of drugs targets mitosis.

PMID- 15956647
TI  - Cancer data coming soon to laptops everywhere.

PMID- 15956648
TI  - Stat bite: Age-specific incidence of cancer in European children and adolescents.

PMID- 15956649
TI  - Epidermal growth factor receptor, protein kinase B/Akt, and glioma response to
      erlotinib.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor
      erlotinib (also known as Tarceva or OSI-774) has shown promising response rates
      in malignant gliomas. We investigated the association between expression of EGFR
      and downstream signaling components and the response of malignant gliomas to
      erlotinib in a phase I trial of erlotinib administered either alone or with the
      alkylating agent temozolomide. METHODS: Expression of EGFR and ligand-independent
      EGFRvIII mutant proteins and of phosphorylated protein kinase B (PKB)/Akt in
      specimens from glioma patients were assessed by immunohistochemistry. EGFR gene
      amplification was evaluated by fluorescence in situ hybridization. Mutations in
      PTEN and EGFR were assessed by polymerase chain reaction amplification and
      sequencing. Response was evaluated by sequential magnetic resonance imaging every
      2 months. The Cochran-Mantel-Haenzel test was used to assess associations between
      biomarker status and response. All statistical tests were two-sided. RESULTS: Of
      41 glioma patients, eight responded to treatment. Response to erlotinib was
      associated with EGFR expression (P = .07) and EGFR amplification (P = .08). These
      associations were stronger and statistically significant among the 29 patients
      initially diagnosed with glioblastoma multiforme (P = .03 and P = .02,
      respectively). Among six responders with sufficient tumor tissue, none had
      EGFRvIII mutations. None of the 22 tumors with high levels of phosphorylated
      PKB/Akt responded to erlotinib treatment, whereas eight of the 18 tumors with low
      levels of phosphorylated PKB/Akt responded to erlotinib treatment (P < .001). The
      level of phosphorylated PKB/Akt was also associated with time to progression (P <
      .001). CONCLUSIONS: Among glioma patients, those with glioblastoma multiforme
      tumors who have high levels of EGFR expression and low levels of phosphorylated
      PKB/Akt had better response to erlotinib treatment than those with low levels of
      EGFR expression and high levels of phosphorylated PKB/Akt.

PMID- 15956650
TI  - Cost-effectiveness of human papillomavirus DNA testing in the United Kingdom, The
      Netherlands, France, and Italy.
AB  - BACKGROUND: European countries with established cytology-based screening programs
      for cervical cancer will soon face decisions about whether to incorporate human
      papillomavirus (HPV) DNA testing and what strategies will be most cost-effective.
      We assessed the cost-effectiveness of incorporating HPV DNA testing into existing
      cervical cancer screening programs in the United Kingdom, The Netherlands,
      France, and Italy. METHODS: We created a computer-based model of the natural
      history of cervical carcinogenesis for each using country-specific data on
      cervical cancer risk and compared each country's current screening policy with
      two new strategies: 1) cytology throughout a woman's lifetime, using HPV DNA
      testing as a triage strategy for equivocal cytology results ("HPV triage"), as
      well as 2) cytology until age 30 years and HPV DNA testing in combination with
      cytology in women more than 30 years of age ("combination testing"). Outcomes
      included reduction in lifetime cervical cancer risk, increase in life expectancy,
      lifetime costs, and incremental cost-effectiveness ratios, expressed as cost per
      year of life saved. We explored alternative protocols and conducted sensitivity
      analysis on key parameters of the model over a relevant range of values to
      identify the most cost-effective options for each country. RESULTS: Both HPV DNA
      testing strategies, HPV triage and combination testing, were more effective than
      each country's status quo screening policy. Incremental cost-effectiveness ratios
      for HPV triage were less than $13,000 per year of life saved, whereas those for
      combination testing ranged from $9800 to $75,900 per year of life saved,
      depending on screening interval. We identified options that would be very cost
      effective (i.e., cost-effectiveness ratio less than the gross domestic product
      per capita) in each of the four countries. CONCLUSIONS: HPV DNA testing has the
      potential to improve health benefits at a reasonable cost compared with current
      screening policies in four European countries.

PMID- 15956651
TI  - Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE
      study.
AB  - BACKGROUND: Infection with human papillomavirus (HPV) is causally linked to the
      development of anal and cervical cancer. In the United States, the incidence of
      anal cancer among men who have sex with men (MSM) is higher than the incidence of
      cervical cancer among women. Anal squamous intraepithelial lesions (ASILs) are
      anal cancer precursors comprising low-grade squamous intraepithelial lesions
      (LSILs) and high-grade squamous intraepithelial lesions (HSILs). The prevalence
      of cervical cancer precursor lesions peaks at around 30 years of age. The age
      related prevalence of ASILs in HIV-negative MSM is unknown. METHODS: We conducted
      a cross-sectional analysis of the prevalence and determinants of ASILs in 1262
      HIV-negative MSM aged 18-89 years recruited from four U.S. cities. Anal cytology
      and behavioral data were obtained. Anal HPV infection status was assessed by
      polymerase chain reaction. Independent predictors of ASILs were identified using
      logistic regression. All statistical tests were two-sided. RESULTS: The
      prevalences of LSILs and HSILs were 15% and 5%, respectively, and did not change
      with age. In a multivariable analysis, the risk of LSILs was associated with
      having more than five male receptive anal sex partners (P = .03), any use of
      poppers (alkyl nitrites) in the previous 6 months [odds ratio (OR) = 1.6, 95%
      confidence interval (CI) = 1.1 to 2.5; P = .03] or use of injection drugs two or
      more times per month during the previous 6 months [OR = 19, 95% CI = 1.3 to 277;
      P = .03], older age at first receptive anal intercourse (P = .004), and infection
      with a greater number of HPV types (P < .001 for linear trend). The risk of HSILs
      was associated with any anal HPV infection (OR = 3.2, 95% CI = 1.1 to 9.4; P =
      .039) and infection with an increasing number of HPV types (P < .001 for linear
      trend). CONCLUSIONS: Sexually active HIV-negative MSM in all age groups have a
      high prevalence of ASILs, possibly reflecting their ongoing sexual exposure to
      HPV.

PMID- 15956652
TI  - Meat, fish, and colorectal cancer risk: the European Prospective Investigation
      into cancer and nutrition.
AB  - BACKGROUND: Current evidence suggests that high red meat intake is associated
      with increased colorectal cancer risk. High fish intake may be associated with a
      decreased risk, but the existing evidence is less convincing. METHODS: We
      prospectively followed 478 040 men and women from 10 European countries who were
      free of cancer at enrollment between 1992 and 1998. Information on diet and
      lifestyle was collected at baseline. After a mean follow-up of 4.8 years, 1329
      incident colorectal cancers were documented. We examined the relationship between
      intakes of red and processed meat, poultry, and fish and colorectal cancer risk
      using a proportional hazards model adjusted for age, sex, energy (nonfat and fat
      sources), height, weight, work-related physical activity, smoking status, dietary
      fiber and folate, and alcohol consumption, stratified by center. A calibration
      substudy based on 36 994 subjects was used to correct hazard ratios (HRs) and 95%
      confidence intervals (CIs) for diet measurement errors. All statistical tests
      were two-sided. RESULTS: Colorectal cancer risk was positively associated with
      intake of red and processed meat (highest [>160 g/day] versus lowest [<20 g/day]
      intake, HR = 1.35, 95% CI = 0.96 to 1.88; Ptrend = .03) and inversely associated
      with intake of fish (>80 g/day versus <10 g/day, HR = 0.69, 95 % CI = 0.54 to
      0.88; Ptrend<.001), but was not related to poultry intake. Correcting for
      measurement error strengthened the associations between colorectal cancer and red
      and processed meat intake (per 100-g increase HR = 1.25, 95% CI =1.09 to 1.41,
      Ptrend = .001 and HR = 1.55, 95% CI = 1.19 to 2.02, Ptrend = .001 before and
      after calibration, respectively) and for fish (per 100 g increase HR = 0.70, 95%
      CI = 0.57 to 0.87, Ptrend<.001 and HR = 0.46, 95% CI = 0.27 to 0.77, Ptrend =
      .003; before and after correction, respectively). In this study population, the
      absolute risk of development of colorectal cancer within 10 years for a study
      subject aged 50 years was 1.71% for the highest category of red and processed
      meat intake and 1.28% for the lowest category of intake and was 1.86% for
      subjects in the lowest category of fish intake and 1.28% for subjects in the
      highest category of fish intake. CONCLUSIONS: Our data confirm that colorectal
      cancer risk is positively associated with high consumption of red and processed
      meat and support an inverse association with fish intake.

PMID- 15956653
TI  - Hemochromatosis gene mutations, body iron stores, dietary iron, and risk of
      colorectal adenoma in women.
AB  - BACKGROUND: Some experimental evidence suggests that iron may play a role in
      colorectal carcinogenesis, but human data for this role have been conflicting,
      possibly because of problems related to study design or measurement of iron
      exposure. We assessed dietary iron intake and genetic and biochemical markers of
      iron status in a prospective, nested case-control study of women enrolled in the
      Nurses' Health Study. METHODS: Among 32 826 women who provided a blood specimen,
      we identified 527 women with colorectal adenoma and 527 matched control subjects
      who underwent endoscopy but were not diagnosed with adenoma after blood
      collection. We assessed iron intake, mutations in the HFE gene that are
      associated with hereditary hemochromatosis (i.e., H63D and C282Y), and plasma
      biochemical measures of total body iron, including transferrin saturation and the
      ratio of the concentrations of transferrin receptors to ferritin. Logistic
      regression models were used to estimate relative risks (RR) and 95% confidence
      intervals (CI). All statistical tests were two-sided. RESULTS: Women with any HFE
      gene mutation had higher total body iron stores, as reflected by higher
      transferrin saturations (P < .001) and lower levels of the ratio of transferrin
      receptors to ferritin (P = .02), than women with no HFE gene mutation. However,
      HFE gene mutations were not associated with risk of adenoma (multivariable RR =
      1.08, 95% CI = 0.83 to 1.39; P = .58). Moreover, comparison of extreme categories
      showed no associations between adenoma and the extent of transferrin saturation
      (multivariable RR = 0.96, 95% CI = 0.63 to 1.47; Ptrend = .66), the ratio of
      transferrin receptors to ferritin (multivariable RR = 0.98, 95% CI, 0.60 to 1.60;
      Ptrend = .99), or dietary iron intake (multivariable RR = 1.04, 95% CI = 0.68 to
      1.57; Ptrend = .94). CONCLUSIONS: Although our study used several distinct
      measures of iron status (i.e., genetic mutations, biochemical markers, and
      dietary intake) and a nested case-control design, we did not observe a role for
      iron in the pathogenesis of colorectal neoplasia in women.

PMID- 15956654
TI  - Limits of predictive models using microarray data for breast cancer clinical
      treatment outcome.
AB  - Data from microarray studies have been used to develop predictive models for
      treatment outcome in breast cancer, such as a recently proposed predictive model
      for antiestrogen response after tamoxifen treatment that was based on the
      expression ratio of two genes. We attempted to validate this model on an
      independent cohort of 58 patients with resectable estrogen receptor-positive
      breast cancer. We measured expression of the genes HOXB13 and IL17BR with real
      time-quantitative polymerase chain reaction and assessed the association between
      their expression and outcome by use of univariate logistic regression, area under
      the receiver-operating-characteristic curve (AUC), a two-sample t test, and a
      Mann-Whitney test. We also applied standard supervised methods to the original
      microarray dataset and to another independent dataset from similar patients to
      estimate the classification accuracy obtainable by using more than two genes in a
      microarray-based predictive model. We could not validate the performance of the
      two-gene predictor on our cohort of samples (relation between outcome and the
      following genes estimated by logistic regression: for HOXB13, odds ratio [OR] =
      1.04, 95% confidence interval [CI] = 0.92 to 1.16, P = .54; for IL17BR, OR =
      0.69, 95% CI = 0.40 to 1.20, P = .18; and for HOXB13/IL17BR, OR = 1.30, 95% CI =
      0.88 to 1.93, P = .18). Similar results were obtained with the AUC, a two-sample
      two-sided t test, and a Mann-Whitney test. In addition, estimates of
      classification accuracies applied to two independent microarray datasets
      highlighted the poor performance of treatment-response predictive models that can
      be achieved with the sample sizes of patients and informative genes to date.

PMID- 15956655
TI  - High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dube
      associated renal tumors.
AB  - The Birt-Hogg-Dube (BHD) syndrome is an inherited genodermatosis characterized by
      a predisposition to hamartomatous skin lesions, pulmonary cysts, and renal
      carcinoma. Seventy-seven renal tumors from 12 patients with germline BHD
      mutations were examined by DNA sequencing to identify somatic mutations in the
      second copy of BHD. Sequence alterations were detected in the majority of renal
      tumors (41 of 77, 53%), with loss of heterozygosity at the BHD locus in a
      minority of additional tumors (14 of 77, 17%). The somatic mutations were
      distributed across the entire gene, and the majority resulted in frameshifts that
      are predicted to truncate the BHD protein. These results support a role for BHD
      as a tumor suppressor gene that predisposes to the development of renal tumors
      when both copies are inactivated.

PMID- 15956656
TI  - Re: Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer
      (Lynch syndrome) and microsatellite instability.

PMID- 15956657
TI  - Re: Accuracy of screening mammography interpretation by characteristics of
      radiologists.

PMID- 15956658
TI  - Re: Clinical trials registration efforts gain some ground.

PMID- 15956659
TI  - Re: A study of the impact of adding HPV types to cervical cancer screening and
      triage tests.

PMID- 15956662
TI  - Portrait of a species: Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii, the first alga subject to a genome project, has been
      the object of numerous morphological, physiological, and genetic studies. The
      organism has two genetically determined mating types (plus and minus) and all
      stages of the simple life cycle can be evoked in culture. In the nearly 60 years
      since the first standard laboratory strains were isolated, numerous crosses and
      exchanges among laboratories have led to some confusion concerning strain
      genealogy. Here we use analyses of the nuclear internal transcribed spacer
      regions and other genetic traits to resolve these issues, correctly identify
      strains currently available, and analyze phylogenetic relationships with all
      other available similar chlamydomonad types. The presence of a 10-bp indel in
      ITS2 in some but not all copies of the nuclear ribosomal cistrons of an
      individual organism, and the changing ratios of these in crosses, provide a tool
      to investigate mechanisms of concerted evolution. The standard C. reinhardtii
      strains, plus C. smithii +, plus the new eastern North American C. reinhardtii
      isolates, comprise one morphological species, one biological species of high
      sexual intercompatibility, and essentially identical ITS sequences (except the
      tip of helix I of ITS2). However, variant RFLP patterns characterize strains from
      each geographic site.

PMID- 15956663
TI  - The [URE3] prion is not conserved among Saccharomyces species.
AB  - The [URE3] prion of Saccharomyces cerevisiae is a self-propagating inactive form
      of the nitrogen catabolism regulator Ure2p. To determine whether the [URE3] prion
      is conserved in S. cerevisiae-related yeast species, we have developed genetic
      tools allowing the detection of [URE3] in Saccharomyces paradoxus and
      Saccharomyces uvarum. We found that [URE3] is conserved in S. uvarum. In
      contrast, [URE3] was not detected in S. paradoxus. The inability of S. paradoxus
      Ure2p to switch to a prion isoform results from the primary sequence of the
      protein and not from the lack of cellular cofactors as heterologous Ure2p can
      propagate [URE3] in this species. Our data therefore demonstrate that [URE3] is
      conserved only in a subset of Saccharomyces species. Implications of our finding
      on the physiological and evolutionary meaning of the yeast [URE3] prion are
      discussed.

PMID- 15956664
TI  - The dominant inhibitory chalcone synthase allele C2-Idf (inhibitor diffuse) from
      Zea mays (L.) acts via an endogenous RNA silencing mechanism.
AB  - The flavonoid pigment pathway in plants has been used as a model system for
      studying gene regulatory mechanisms. C2-Idf is a stable dominant mutation of the
      chalcone synthase gene, c2, which encodes the first dedicated enzyme in this
      biosynthetic pathway of maize. Homozygous C2-Idf plants show no pigmentation.
      This allele also inhibits expression of functional C2 alleles in heterozygotes,
      producing a less pigmented condition instead of the normal deeply pigmented
      phenotype. To explore the nature of this effect, the C2-Idf allele was cloned.
      The gene structure of the C2-Idf haplotype differs substantially from that of the
      normal c2 gene in that three copies are present. Two of these are located in
      close proximity to each other in a head-to-head orientation and the third is
      closely linked. Previous experiments showed that the lower level of pigmentation
      in heterozygotes is correlated with reduced enzyme activity and low steady-state
      mRNA levels. We found that c2 transcription occurs in nuclei of C2-Idf/C2
      heterozygotes, but mRNA does not accumulate, suggesting that the inhibition is
      mediated by RNA silencing. Infection of C2-Idf/C2 heterozygotes with viruses that
      carry suppressors of RNA silencing relieved the phenotypic inhibition, restoring
      pigment production and mRNA levels. Finally, we detected small interfering RNAs
      (siRNAs) in plants carrying C2-Idf, but not in plants homozygous for the wild
      type C2 allele. Together, our results indicate that the inhibitory effect of C2
      Idf occurs through RNA silencing.

PMID- 15956661
TI  - Contrasting patterns of polymorphism and divergence on the Z chromosome and
      autosomes in two Ficedula flycatcher species.
AB  - In geographic areas where pied and collared flycatchers (Ficedula hypoleuca and
      F. albicollis) breed in sympatry, hybridization occurs, leading to gene flow
      (introgression) between the two recently diverged species. Notably, while such
      introgression is observable at autosomal loci it is apparently absent at the Z
      chromosome, suggesting an important role for genes on the Z chromosome in
      creating reproductive isolation during speciation. To further understand the role
      of Z-linked loci in the formation of new species, we studied genetic variation of
      the two species from regions where they live in allopatry. We analyzed patterns
      of polymorphism and divergence in introns from 9 Z-linked and 23 autosomal genes
      in pied and collared flycatcher males. Average variation on the Z chromosome is
      greatly reduced compared to neutral expectations based on autosomal diversity in
      both species. We also observe significant heterogeneity between patterns of
      polymorphism and divergence at Z-linked loci and a relative absence of
      polymorphisms that are shared by the two species on the Z chromosome compared to
      the autosomes. We suggest that these observations may indicate the action of
      recurrent selective sweeps on the Z chromosome during the evolution of the two
      species, which may be caused by sexual selection acting on Z-linked genes.
      Alternatively, reduced variation on the Z chromosome could result from
      substantially higher levels of introgression at autosomal than at Z-linked loci
      or from a complex demographic history, such as a population bottleneck.

PMID- 15956665
TI  - Molecular evidence for transcription of genes on a B chromosome in Crepis
      capillaris.
AB  - Dispensable, supernumerary (B) chromosomes are found in diverse eukaryotic
      species. The origin and genetic consequences of B chromosomes have been the
      subjects of speculation for more than a century. Until now, there has been no
      molecular evidence that B chromosome DNA is transcribed and there is no
      unequivocal evidence as to their origin. B chromosomes are considered to be
      genetically inert although they appear to cause a variety of phenotypic effects.
      We report that members of one of two ribosomal RNA gene families that are
      confined to the B chromosomes of a plant, Crepis capillaris, are transcribed-
      thus providing the first molecular evidence of gene activity on B chromosomes.
      Sequence analysis of part of the A and B chromosome rRNA genes, together with
      comparisons with related species, indicates that the B chromosome rRNA genes
      originate from the A chromosome.

PMID- 15956666
TI  - Identification of genetic loci that interact with cut during Drosophila wing
      margin development.
AB  - The Drosophila selector gene cut is a hierarchal regulator of external sensory
      organ identity and is required to pattern the sensory and nonsensory cells of the
      wing margin. Cut performs the latter function, in part, by maintaining expression
      of the secreted morphogen encoded by wingless (wg). We find that Cut is required
      for wing-margin sensory organ specification in addition to and independently of
      Wg maintenance. In addition, we performed a genetic modifier screen to identify
      other genes that interact with cut in the regulation of wing-margin patterning.
      In total, 45 genetic loci (35 gain-of-function and 10 loss-of-function loci) were
      identified by virtue of their ability to suppress the wing-margin defects
      resulting from gypsy retrotransposon-mediated insulation of the cut wing-margin
      enhancer. Further genetic characterization identified several subgroups of
      candidate cut interacting loci. One group consists of putative regulators of
      gypsy insulator activity. A second group is potentially required for the
      regulation of Cut expression and/or activity and includes longitudinals lacking,
      a gene that encodes a family of BTB-domain zinc-finger transcription factors. A
      third group, which includes a component of the Brahma chromatin remodeling
      complex encoded by moira, affects the level of Cut expression in two opposing
      ways by suppressing the gypsy-mediated ct(K) phenotype and enhancing the non
      gypsy ct(53d) phenotype. This suggests that the Brahma complex modulates both
      enhancer-controlled transcription and gypsy-mediated gene insulation of the cut
      locus.

PMID- 15956667
TI  - NinR- and red-mediated phage-prophage marker rescue recombination in Escherichia
      coli: recovery of a nonhomologous immlambda DNA segment by infecting lambdaimm434
      phages.
AB  - We examined the requirement of lambda recombination functions for marker rescue
      of cryptic prophage genes within the Escherichia coli chromosome. We infected
      lysogenic host cells with lambdaimm434 phages and selected for recombinant
      immlambda phages that had exchanged the imm434 region of the infecting phage for
      the heterologous 2.6-kb immlambda region from the prophage. Phage-encoded
      activity, provided by either Red or NinR functions, was required for the
      substitution. Red(-) phages with DeltaNinR, internal NinR deletions of rap-ninH,
      or orf-ninC were 117-, 12-, and 5-fold reduced for immlambda rescue in a Rec(+)
      host, suggesting the participation of several NinR activities. RecA was essential
      for NinR-dependent immlambda rescue, but had slight influence on Red-dependent
      rescue. The host recombination activities RecBCD, RecJ, and RecQ participated in
      NinR-dependent recombination while they served to inhibit Red-mediated immlambda
      rescue. The opposite effects of several host functions toward NinR- and Red
      dependent immlambda rescue explains why the independent pathways were not
      additive in a Rec(+) host and why the NinR-dependent pathway appeared dominant.
      We measured the influence of the host recombination functions and DnaB on the
      appearance of orilambda-dependent replication initiation and whether orilambda
      replication initiation was required for immlambda marker rescue.

PMID- 15956669
TI  - Genetic regulation of gene expression during shoot development in Arabidopsis.
AB  - The genetic control of gene expression during shoot development in Arabidopsis
      thaliana was analyzed by combining quantitative trait loci (QTL) and microarray
      analysis. Using oligonucleotide array data from 30 recombinant inbred lines
      derived from a cross of Columbia and Landsberg erecta ecotypes, the Arabidopsis
      genome was scanned for marker-by-gene linkages or so-called expression QTL
      (eQTL). Single-feature polymorphisms (SFPs) associated with sequence disparities
      between ecotypes were purged from the data. SFPs may alter the hybridization
      efficiency between cDNAs from one ecotype with probes of another ecotype. In
      genome scans, five eQTL hot spots were found with significant marker-by-gene
      linkages. Two of the hot spots coincided with classical QTL conditioning shoot
      regeneration, suggesting that some of the heritable gene expression changes
      observed in this study are related to differences in shoot regeneration
      efficiency between ecotypes. Some of the most significant eQTL, particularly
      those at the shoot regeneration QTL sites, tended to show cis-chromosomal
      linkages in that the target genes were located at or near markers to which their
      expression was linked. However, many linkages of lesser significance showed
      expected "trans-effects," whereby a marker affects the expression of a target
      gene located elsewhere on the genome. Some of these eQTL were significantly
      linked to numerous genes throughout the genome, suggesting the occurrence of
      large groups of coregulated genes controlled by single markers.

PMID- 15956668
TI  - Hypervariable noncoding sequences in Saccharomyces cerevisiae.
AB  - Compared to protein-coding sequences, the evolution of noncoding sequences and
      the selective constraints placed on these sequences is not well characterized. To
      compare the evolution of coding and noncoding sequences, we have conducted a
      survey for DNA polymorphism at five randomly chosen loci among a diverse
      collection of 81 strains of Saccharomyces cerevisiae. Average rates of both
      polymorphism and divergence are 40% lower at noncoding sites and 90% lower at
      nonsynonymous sites in comparison to synonymous sites. Although noncoding and
      coding sequences show substantial variability in ratios of polymorphism to
      divergence, two of the loci, MLS1 and PDR10, show a higher rate of polymorphism
      at noncoding compared to synonymous sites. The high rate of polymorphism is not
      accompanied by a high rate of divergence and is limited to a few small regions.
      These hypervariable regions include sites with three segregating bases at a
      single site and adjacent polymorphic sites. We show that this clustering of
      polymorphic sites is significantly greater than one would expect on the basis of
      the spacing between polymorphic fourfold degenerate sites. Although hypervariable
      noncoding sequences could result from selection on regulatory mutations, they
      could also result from transient mutational hotspots.

PMID- 15956670
TI  - Neurospora strains harboring mitochondrial disease-associated mutations in iron
      sulfur subunits of complex I.
AB  - We subjected the genes encoding the 19.3-, 21.3c-, and 51-kDa iron-sulfur
      subunits of respiratory chain complex I from Neurospora crassa to site-directed
      mutagenesis to mimic mutations in human complex I subunits associated with
      mitochondrial diseases. The V135M substitution was introduced into the 19.3-kDa
      cDNA, the P88L and R111H substitutions were separately introduced into the 21.3c
      kDa cDNA, and the A353V and T435M alterations were separately introduced into the
      51-kDa cDNA. The altered cDNAs were expressed in the corresponding null-mutants
      under the control of a heterologous promoter. With the exception of the A353V
      polypeptide, all mutated subunits were able to promote assembly of a functional
      complex I, rescuing the phenotypes of the respective null-mutants. Complex I from
      these strains displays spectroscopic and enzymatic properties similar to those
      observed in the wild-type strain. A decrease in total complex I amounts may be
      the major impact of the mutations, although expression levels of mutant genes
      from the heterologous promoter were sometimes lower and may also account for
      complex I levels. We discuss these findings in relation to the involvement of
      complex I deficiencies in mitochondrial disease.

PMID- 15956671
TI  - The dst1 gene involved in mushroom photomorphogenesis of Coprinus cinereus
      encodes a putative photoreceptor for blue light.
AB  - The homobasidiomycete Coprinus cinereus exhibits remarkable photomorphogenesis
      during fruiting-body development. Under proper light conditions, fruiting-body
      primordia proceed to the maturation phase in which basidia in the pileus undergo
      meiosis, producing sexual spores, followed by stipe elongation and pileus
      expansion for efficient dispersal of the spores. In the continuous darkness,
      however, the primordia do not proceed to the maturation phase but are etiolated:
      the pileus and stipe tissues at the upper part of the primordium remain
      rudimentary and the basal part of the primordium elongates, producing "dark
      stipe." In this study we genetically analyzed five strains that produce dark
      stipes even if light conditions promoting the maturation are given and then
      characterized one of them, Uar801 (dst1-1). The dst1 gene was cloned as a DNA
      fragment that rescues the dst1-1 mutation. Dst1 is predicted to be a protein of
      1175 amino acids that contains two PAS domains, a coiled-coil structure, and a
      putative, glutamine-rich, transcriptional activation domain (AD). One of the PAS
      domains exhibits significant similarity to the LOV domains of known blue-light
      receptors, suggesting that Dst1 is a blue-light receptor of C. cinereus. The dst1
      1 mutation is predicted to truncate the putative AD in the C-terminal region.

PMID- 15956672
TI  - RecD plays an essential function during growth at low temperature in the
      antarctic bacterium Pseudomonas syringae Lz4W.
AB  - The Antarctic psychrotrophic bacterium Pseudomonas syringae Lz4W has been used as
      a model system to identify genes that are required for growth at low temperature.
      Transposon mutagenesis was carried out to isolate mutant(s) of the bacterium that
      are defective for growth at 4 degrees but normal at 22 degrees . In one such cold
      sensitive mutant (CS1), the transposon-disrupted gene was identified to be a
      homolog of the recD gene of several bacteria. Trans-complementation and freshly
      targeted gene disruption studies reconfirmed that the inactivation of the recD
      gene leads to a cold-sensitive phenotype. We cloned, sequenced, and analyzed
      approximately 11.2 kbp of DNA from recD and its flanking region from the
      bacterium. recD was the last gene of a putative recCBD operon. The RecD ORF was
      694 amino acids long and 40% identical (52% similar) to the Escherichia coli
      protein, and it could complement the E. coli recD mutation. The recD gene of E.
      coli, however, could not complement the cold-sensitive phenotype of the CS1
      mutant. Interestingly, the CS1 strain showed greater sensitivity toward the DNA
      damaging agents, mitomycin C and UV. The inactivation of recD in P. syringae also
      led to cell death and accumulation of DNA fragments of approximately 25-30 kbp in
      size at low temperature (4 degrees ). We propose that during growth at a very low
      temperature the Antarctic P. syringae is subjected to DNA damage, which requires
      direct participation of a unique RecD function. Additional results suggest that a
      truncated recD encoding the N-terminal segment of (1-576) amino acids is
      sufficient to support growth of P. syringae at low temperature.

PMID- 15956673
TI  - Optimal allocation in designs for assessing heterosis from cDNA gene expression
      data.
AB  - Heterosis is defined as the superiority of a hybrid cross over its two parents.
      Plant and animals breeders have long been exploiting heterosis, but the causes of
      this phenomenon are as yet only partly understood. Recently, chip technology has
      opened up the opportunity to study heterosis at the gene expression level. This
      article considers the cDNA chip technology, which allows assaying two genotypes
      simultaneously on the same chip. Heterosis involves the response of at least
      three genotypes (two parents and their hybrid), so a chip or microarray
      constitutes an incomplete block, which raises a design problem specific to
      heterosis studies. The question to be answered is how genotype pairs should be
      allocated to chips. We address this design problem for two types of heterosis:
      midparent heterosis and better-parent heterosis. The general picture emerging
      from our results is that most of the resources should be allocated to parent
      hybrid pairs, while chips with parent-parent pairs or hybrid-reciprocal pairs
      should be used sparingly or not at all.

PMID- 15956674
TI  - Quantitative trait Loci analysis using the false discovery rate.
AB  - False discovery rate control has become an essential tool in any study that has a
      very large multiplicity problem. False discovery rate-controlling procedures have
      also been found to be very effective in QTL analysis, ensuring reproducible
      results with few falsely discovered linkages and offering increased power to
      discover QTL, although their acceptance has been slower than in microarray
      analysis, for example. The reason is partly because the methodological aspects of
      applying the false discovery rate to QTL mapping are not well developed. Our aim
      in this work is to lay a solid foundation for the use of the false discovery rate
      in QTL mapping. We review the false discovery rate criterion, the appropriate
      interpretation of the FDR, and alternative formulations of the FDR that appeared
      in the statistical and genetics literature. We discuss important features of the
      FDR approach, some stemming from new developments in FDR theory and methodology,
      which deem it especially useful in linkage analysis. We review false discovery
      rate-controlling procedures--the BH, the resampling procedure, and the adaptive
      two-stage procedure-and discuss the validity of these procedures in single- and
      multiple-trait QTL mapping. Finally we argue that the control of the false
      discovery rate has an important role in suggesting, indicating the significance
      of, and confirming QTL and present guidelines for its use.

PMID- 15956675
TI  - A comparison of three estimators of the population-scaled recombination rate:
      accuracy and robustness.
AB  - We have performed simulations to assess the performance of three population
      genetics approximate-likelihood methods in estimating the population-scaled
      recombination rate from sequence data. We measured performance in two ways:
      accuracy when the sequence data were simulated according to the (simplistic)
      standard model underlying the methods and robustness to violations of many
      different aspects of the standard model. Although we found some differences
      between the methods, performance tended to be similar for all three methods.
      Despite the fact that the methods are not robust to violations of the underlying
      model, our simulations indicate that patterns of relative recombination rates
      should be inferred reasonably well even if the standard model does not hold. In
      addition, we assess various techniques for improving the performance of
      approximate-likelihood methods. In particular we find that the composite
      likelihood method of Hudson (2001) can be improved by including log-likelihood
      contributions only for pairs of sites that are separated by some prespecified
      distance.

PMID- 15956676
TI  - Genome-wide characterization of Tetrahymena thermophila chromosome breakage
      sites. II. Physical and genetic mapping.
AB  - The chromosomes of the macronuclear (expressed) genome of Tetrahymena thermophila
      are generated by developmental fragmentation of the five micronuclear (germline)
      chromosomes. This fragmentation is site specific, directed by a conserved
      chromosome breakage sequence (Cbs element). An accompanying article in this issue
      reports the development of a successful scheme for the genome-wide cloning and
      identification of functional chromosome breakage sites. This article reports the
      physical and genetic characterization of 30 functional chromosome breakage
      junctions. Unique sequence tags and physical sizes were obtained for the pair of
      macronuclear chromosomes generated by fragmentation at each Cbs. Cbs-associated
      polymorphisms were used to genetically map 11 junctions to micronuclear linkage
      groups and macronuclear coassortment groups. Two pairs of junctions showed
      statistically significant similarity of the sequences flanking the Cbs,
      suggestive of relatively recent duplications of entire Cbs junctions during
      Tetrahymena genome evolution. Two macronuclear chromosomes that lose at least one
      end in an age-related manner were also identified. The whole-genome shotgun
      sequencing of the Tetrahymena macronucleus has recently been completed at The
      Institute for Genome Research (TIGR). By providing unique sequence from natural
      ends of macronuclear chromosomes, Cbs junctions will provide useful sequence tags
      for relating macro- and micronuclear genetic, physical, and whole-genome sequence
      maps.

PMID- 15956677
TI  - Genome-wide characterization of tetrahymena thermophila chromosome breakage
      sites. I. Cloning and identification of functional sites.
AB  - The chromosomes of the macronuclear (expressed) genome of Tetrahymena thermophila
      are generated by developmental fragmentation of the five micronuclear (germline)
      chromosomes. This fragmentation is site specific and directed by a conserved 15
      bp chromosome breakage sequence (Cbs element). This article reports the
      construction of a library enriched for chromosome breakage junctions and the
      development of a successful scheme for the genome-wide isolation and
      characterization of functional Cbs junctions. Twenty-three new Cbs junctions were
      characterized and each was assigned to a specific micronuclear chromosome or
      chromosome arm. Two distinct previously unreported variant chromosome breakage
      sequences were found, each in two or more functional Cbs elements. Analysis of
      natural Cbs junctions confirmed that microheterogeneity in the macronuclear
      telomere addition site is associated with chromosome fragmentation. The physical
      and genetic characterization of these functional chromosome breakage junctions is
      reported in the accompanying article in this issue. The whole-genome shotgun
      sequencing and auto-assembly phase of the Tetrahymena Genome Initiative has
      recently been completed at The Institute for Genome Research (TIGR). By providing
      unique sequence from the natural ends of macronuclear chromosomes, Cbs junctions
      characterized in the work reported here will serve as useful sequence tags for
      relating macro- and micronuclear genetic, physical, and sequence maps.

PMID- 15956679
TI  - Relaxin research in the postgenomic era.
AB  - Because of the coevolution of ligands and their cognate receptors, analysis of
      human genomic sequences allows prediction of the pairing of these elements.
      Initially, we identified a group of five human leucine-rich repeat-containing G
      protein-coupled receptor (LGR) genes homologous to LH, FSH, and TSH receptors.
      Based on common phenotypes of INSL3 null mice and transgenic mice with LGR8 gene
      deletion, we hypothesized that INSL3, relaxin, and related genes are likely
      ligands for the paralogous LGR7 and LGR8 genes. Matching the relaxin family
      peptides with these two orphan LGRs led to the finding that relaxin is capable of
      activating LGR7 and LGR8 through the Gs pathway. In addition, INSL3 and relaxin 3
      were found to be specific ligands for LGR8 and LGR7, respectively. Based on the
      known production of INLS3 by testicular Leydig cells and ovarian theca cells, we
      demonstrated the expression of the INSL3 receptor LGR8 in oocytes in ovary and in
      male germ cells in the testis. Furthermore, we found that LH stimulates INSL3
      transcripts in ovarian theca and testicular Leydig cells. INSL3, in turn, binds
      LGR8 expressed in germ cells to initiate the meiotic progression of arrested
      oocytes in preovulatory follicles in vitro and in vivo and to suppress male germ
      cell apoptosis in vivo. INSL3 interacts with germ cells to activate the
      inhibitory G protein, thus leading to decreases in cAMP production. Our data
      demonstrate the importance of the INSL3-LGR8 paracrine system in mediating
      gonadotropic actions in both ovary and testis.

PMID- 15956680
TI  - Characterization of the mouse and rat relaxin receptors.
AB  - Rodent models have been used for many years to probe the actions of relaxin.
      Identification of the orthologs of human leucine-rich repeat-containing g-protein
      coupled receptor 7 (LGR7), the relaxin receptor, in mouse and rat will enable
      characterization of the response of LGR7 to relaxin in these species. Partial
      LGR7 homologous sequences from mouse and rat were discovered in the Celera and
      NCBI gene databases, amplified, cloned, and sequenced. At the protein level,
      mouse and rat LGR7 are 85.2% and 85.7% identical to human LGR7. Mouse and rat
      LGR7 were able to bind to and be activated by relaxin ligands.

PMID- 15956678
TI  - Adult myogenesis in Drosophila melanogaster can proceed independently of myocyte
      enhancer factor-2.
AB  - Myocyte enhancer factor-2 (MEF2) is a transcription factor that is necessary for
      embryonic muscle development in Drosophila and vertebrates; however, whether this
      factor is required during later muscle development remains largely unknown. Using
      heteroallelic combinations of different Mef2 mutant alleles, we isolated and
      characterized a temperature-sensitive combination. Through temperature-shift
      experiments, we obtained adult animals that were lacking proper MEF2 function.
      Many of these individuals died as mature pupae, and those that eclosed showed
      poor locomotion and an inability to fly. Histological analysis of these animals
      revealed a requirement for MEF2 in skeletal muscle patterning, although these
      animals had strikingly normal amounts of muscle tissue. Using quantitative
      polymerase chain reaction, we determined that expression of the MEF2-regulated
      actin gene Act57B was severely reduced in these animals. By contrast myofibrillar
      actin genes unique to the adult stage were only mildly affected. Since MEF2
      mutant adults were still capable of forming muscle tissue, we conclude that MEF2
      is required for the expression of only a subset of muscle structural genes in the
      adult. These results indicate that additional muscle-specific factors function to
      control the myogenesis of complex and diverse muscle in the adult.

PMID- 15956681
TI  - Characterization of the rat INSL3 receptor.
AB  - Human LGR8, initially discovered as a low-affinity relaxin receptor, has now been
      characterized as the INSL3 receptor. To investigate LGR8 function in the rat, an
      LGR8 ortholog was identified in the rat genome, and the full-length sequence was
      cloned and expressed. Rat LGR8 bound INSL3 with high affinity, clearly
      demonstrating that it is the rat INSL3 receptor. Interestingly, native rat
      relaxin did not activate rat LGR8, indicating that relaxin is not an endogenous
      ligand for rat LGR8. LGR8 mRNA expression was demonstrated in the gubernaculum at
      the time of testis descent and in the testis associated with germ cells.

PMID- 15956682
TI  - Identification of binding sites with differing affinity and potency for relaxin
      analogues on LGR7 and LGR8 receptors.
AB  - This study defines the pharmacologic characteristics of LGR7 and LGR8, the
      receptors for H2 relaxin and INSL3 respectively, and determines the relative
      activity of relaxin-related peptides. We show, for the first time, the
      availability of two binding sites at LGR8 and confirm the presence of two sites
      at LGR7. Relaxin-related peptides had differing rank orders of affinity and
      potency at LGR7 and LGR8, but chimeric receptors were highly similar to their
      ectodomain-origin native receptors. The high-affinity site on the ectodomain
      coupled efficiently to cAMP production, whereas the low-affinity site in the
      transmembrane region coupled with decreased efficiency.

PMID- 15956683
TI  - LGR7-truncate is a splice variant of the relaxin receptor LGR7 and is a relaxin
      antagonist in vitro.
AB  - The relaxin receptor (LGR7) and the insulin-like peptide 3 (INSL3) receptor
      (LGR8) are unique LGR family members in possessing a single, functionally
      important amino terminal LDL-A module.1 Mouse and rat cDNA was screened for LGR7
      and LGR7 splice variant expression. A uterus-specific exon 4 deleted variant was
      identified and named LGR7-Truncate. Deletion of exon 4 results in a premature
      stop codon and a transcript that putatively encodes a secreted protein containing
      LGR7's LDL-A module. Expression of LGR7-Truncate with LGR7 in HEK-293T cells
      resulted in decreased relaxin-induced signaling of LGR7. LGR7-Truncate is
      potentially an endogenous regulator of LGR7 signaling.

PMID- 15956684
TI  - The human LGR7 low-density lipoprotein class A module requires calcium for
      structure.
AB  - The relaxin and INSL3 receptors, LGR7 and LGR8, are the only human G-protein
      coupled receptors to contain a low-density lipoprotein class-A (LDL-A) module.
      LDL-A modules are well characterized in a variety of diverse biological functions
      that involve ligand binding to elicit a response. Common features of the LDL-A
      modules characterized to date are the conservation of three disulfide bonds and
      the structural arrangement around a bound calcium ion. In this study we
      recombinantly produce the human LGR7 LDL-A module for NMR studies and demonstrate
      that calicum is required for the module to form a stable and correctly folded
      structure.

PMID- 15956685
TI  - Studies on soluble ectodomain proteins of relaxin (LGR7) and insulin 3 (LGR8)
      receptors.
AB  - The ectodomains of both the relaxin (LGR7) and the INSL3 (LGR8) receptors can be
      expressed on the cell surface using only a single transmembrane domain. These
      membrane-anchored proteins retain the ability to bind relaxin and can be cleaved
      from the cell surface. The subsequent LGR7 protein, 7BP, binds relaxin and can
      act as a functional relaxin antagonist. By contrast, the equivalent LGR8 protein
      8BP does not bind relaxin or antagonize LGR8 activity. The 7BP protein has been
      successfully immobilized onto chemically derivatized surfaces for the capture of
      relaxin peptides and subsequent identification via SELDI-MS analysis.

PMID- 15956686
TI  - The chemistry and biology of human relaxin-3.
AB  - A novel member of the human relaxin subclass of the insulin superfamily was
      recently discovered during a genomics database search and named relaxin-3. Like
      human relaxin-1 and relaxin-2, relaxin-3 is predicted to consist of a two-chain
      structure and three disulfide bonds in a disposition identical to that of
      insulin. To undertake detailed biophysical and biological characterization of the
      peptide, its chemical synthesis was undertaken. In contrast to human relaxin-1
      and relaxin-2, however, relaxin-3 could not be successfully prepared by simple
      combination of the individual chains, thus necessitating recourse to the use of a
      regioselective disulfide bond formation strategy. Solid phase synthesis of the
      separate, selectively S-protected A and B chains followed by their purification
      and the subsequent stepwise formation of each of the three disulfides led to the
      successful acquisition of human relaxin-3. Comprehensive chemical
      characterization confirmed both the correct chain orientation and the integrity
      of the synthetic product. Relaxin-3 was found to bind to and activate native
      relaxin receptors in vitro and stimulate water drinking through central relaxin
      receptors in vivo. Recent studies have demonstrated that relaxin-3 will bind to
      and activate human LGR7, but not LGR8, in vitro. Secondary structural analysis
      showed it to adopt a less ordered confirmation than either relaxin-1 or relaxin
      2, reflecting the presence in the former of a greater percentage of nonhelical
      forming amino acids. NMR spectroscopy and simulated annealing calculations were
      used to determine the three-dimensional structure of relaxin-3 and to identify
      key structural differences between the human relaxins.

PMID- 15956687
TI  - Recent progress in relaxin-3-related research.
AB  - Relaxin-3 (R3) is the latest member of the insulin (INSL) superfamily, which is
      composed of peptides with diverse sequences held together by characteristic
      disulfide links connecting A and B peptide chains. R3 has nearly exclusive
      expression in the brainstem and was demonstrated to be an additional ligand for
      LGR7. We recently identified R3 as a ligand for two orphan G-protein coupled
      receptors, GPCR135 and GPCR142. The predominant brain expression for both R3 and
      GPCR135, coupled with their high affinity interaction, strongly suggests that R3
      is the endogenous ligand for GPCR135. Both R3 and GPCR135 from different species
      are highly conserved from genetic sequences to in vitro pharmacology. By
      contrast, GPCR142 is a pseudogene in the rat, and the mouse gene is less
      conserved with human GPCR142, suggesting that GPCR142 may have a diminished role
      as a receptor for R3 in the rodent. In addition, the tissue expression pattern of
      GPCR142, which is primarily in peripheral tissue, is drastically different from
      that of R3, suggesting that GPCR142 may have an endogenous ligand other than R3.
      Sequence analysis among INSL/relaxin family members shows that INSL5 is the
      closest member of R3. We were able to demonstrate that INSL-5 is an agonist for
      GPCR142 but not for GPCR135. We also showed that the mRNA expression pattern of
      INSL-5 overlaps with that of GPCR142. By substituting the A chain of R3 with the
      A chain of INSL-5, we devised a chimeric peptide (R3/I5) that is about 1000-fold
      selective for GPCR135 and GPCR142 over LGR7. Autoradiographic distribution of
      GPCR135 binding sites using [125I]R3/I5 in rat brain shows that GPCR135 receptor
      is most prominent in areas known for the processing of sensory signals.

PMID- 15956688
TI  - Receptors for relaxin family peptides.
AB  - Recent studies have identified four receptors that are the physiological targets
      for relaxin family peptides. All are class I (rhodopsin like) G-protein-coupled
      receptors with LGR7 (RXFP1) and LGR8 (RXFP2) being type C leucine-rich repeat
      containing receptors, whereas GPCR135 (RXFP3) and GPCR142 (RXFP4) resemble
      receptors that respond to small peptides such as somatostatin and angiotensin II.
      The cognate ligands for the receptors have been identified: relaxin for RXFP1;
      INSL3 for RXFP2; relaxin 3 for RXFP3 and INSL5 for RXFP4. RXFP1 and RXFP2
      receptors produce increases in intracellular cAMP levels upon stimulation,
      although the response is complex and contains a component sensitive to PI-3
      kinase inhibitors. There is also evidence that RXFP1 can activate Erk1/2 and
      nitric oxide synthase, and relaxin has been reported to enter cells and activate
      glucocorticoid receptors. In contrast, RXFP3 and RXFP4 couple to Gi by a
      pertussis toxin-sensitive mechanism to cause inhibition of cAMP production. Now
      that the receptors for relaxin family peptides and their cognate ligands have
      been identified, we suggest a nomenclature for both the peptides and the
      receptors that we hope will be helpful to researchers in this rapidly advancing
      field.

PMID- 15956689
TI  - Expression of porcine prorelaxin in transgenic tobacco.
AB  - In vitro studies demonstrate that porcine relaxin may possess various therapeutic
      effects. In this study, we explore the possibility of expressing porcine relaxin
      in transgenic tobacco. Tobacco was selected because it is a non-food, non-feed
      crop, and recombinant protein production can readily be scaled up. The cDNA of
      porcine preprorelaxin was under the regulation of two different constitutive
      promoters. DNA analysis by polymerase chain reaction verified that all transgenic
      plants contained the correct size of gene insert. Preliminary studies showed the
      presence of putative prorelaxin bands in both silver-stained SDS-PAGE and western
      blot. The results also indicated that tobacco-produced prorelaxin may not be
      properly processed to yield the mature relaxin.

PMID- 15956690
TI  - Genetic targeting of relaxin and insl3 signaling in mice.
AB  - We studied ligand-receptor interactions between relaxin (RLN), insulin-like 3
      peptide (INSL3), and LGR7 and LGR8 receptors. The phenotypic effects of
      deficiency for Lgr7 and Lgr8 receptors, transgenic overexpression of Rln1 and
      Insl3, and different combinations of these mutations in mice were analyzed. It
      was reported that Rln1-deficient mice exhibit abnormal nipple development,
      prolonged parturition, age-related pulmonary fibrosis, and abnormalities in the
      testis and prostate. Mutation of Lgr8 or its cognate ligand Insl3 causes
      cryptorchidism. Mutant females deficient for the Lgr7 receptor have grossly
      undeveloped nipples and are unable to feed their progeny. Parturition is
      prolonged in these females, resulting in a significantly higher number of
      stillborn pups. Histologic analysis of Lgr7 mutant lung tissues demonstrates
      increased collagen accumulation and perivenular smooth muscle hypertrophy.
      However, Lgr7-deficient males do not exhibit abnormalities of male reproductive
      organs as seen in Rln1 knockout mice. Double-mutant males deficient for Lgr7 and
      Lgr8 have a normal prostate, suggesting that Lgr8 does not account for
      differences in Rln1-/- and Lgr7-/- phenotypes. We also produced mice with
      transgenic overexpression of Rln1 under rat insulin 2 promoter. Rln1 transgenic
      females exhibited increased nipple size, whereas Rln1 transgenic females
      deficient in Lgr7 had undeveloped nipples, indicating that Lgr7 is the only
      receptor for relaxin that mediates this effect. Transgenic overexpression of Rln1
      does not affect gonadal descent in females, and transgenic overexpression of
      Insl3 does not rescue the mutant phenotype of Lgr7-deficient mice, suggesting the
      non-overlapping functions of two signaling pathways. In summary, our data
      indicate that the Insl3/Lgr8 and Rln1/Lgr7 pathways are distinct and separate in
      vivo. Therefore, we propose to rename Lgr8 as Insl3r (Insl3 receptor) and Lgr7 as
      Rlnr (relaxin receptor).

PMID- 15956691
TI  - Mechanisms of relaxin action in the reproductive tract: studies in the relaxin
      deficient (Rlx-/-) mouse.
AB  - The major functions of relaxin (RLX) are associated with female reproductive
      tract physiology, namely, the regulation of biochemical processes involved in
      remodeling of extracellular matrix components in the cervix and vagina at term.
      Studies in RLX-deficient mice (Rlx-/-) demonstrate that although females give
      birth to live young without apparent dystocia, the pubic symphysis is not
      elongated, and they have abnormal cervical and vaginal morphology. The current
      study examined phenotypic differences in collagen, matrix metalloproteinases
      (MMP), and estrogen receptors (ERs) in the cervix and vagina of pregnant Rlx+/+
      and Rlx-/- mice. Neither collagen nor TGFbeta1 mRNA levels in the cervix and
      vagina differed significantly between Rlx+/+ and Rlx-/- at any stage of
      gestation, except on gestation day 18.5, with an increase in alpha(1)-I collagen
      and TGFbeta1 expression in Rlx-/- mice. MMP gene expression was also increased in
      Rlx-/- mice, especially at term. Administration of recombinant H2 RLX (0.05
      microg/microL/h) to Rlx-/- mice for 6 d from gestation day 12.5 caused a
      significant decrease in alpha1-I collagen and MMP-13 gene expression in the
      cervix and vagina, but it had no effect on TGFbeta1. There was also a significant
      reduction in ERbeta expression in RLX-treated Rlx-/- mice. Interestingly, RLX
      treatment caused a significant decrease in LGR7 expression in these reproductive
      tissues. In summary, these data show increases in MMP gene expression in Rlx-/-
      mice that are not correlated with changes in collagen expression. Furthermore, we
      report a novel ER phenotype in the cervix and vagina of Rlx-/- mice.

PMID- 15956692
TI  - Oxytocin and estrogen receptor expression in the myometrium of pregnant relaxin
      deficient (Rlx-/-) mice.
AB  - Relaxin decreases oxytocin-stimulated rat myometrial contractions in vitro. This
      study used pregnant relaxin-deficient (Rlx-/-) mice to investigate the
      interaction between relaxin, oxytocin receptor (OTR), and estrogen receptor (ER)
      expression in the myometrium. Myometrial OTRs were significantly decreased on
      gestation day 18.5 in Rlx-/- mice than in Rlx+/+ mice. An increase in ERalpha in
      Rlx+/+ mice at term was correlated with a decrease in ERbeta, which was not
      observed in Rlx-/- mice. Treatment of Rlx-/- mice with relaxin had no effect on
      OTR, LGR7, or ERalpha expression, but it caused a significant decrease in
      ERbetas.

PMID- 15956694
TI  - Effects of the sucking stimulus on relaxin receptor (LGR7) expression in the
      mammary apparatus of the tammar wallaby (Macropus eugenii).
AB  - Macropodid marsupials suckle young of different ages simultaneously, a phenomenon
      known as asynchronous lactation. The growth of the mammary glands supporting
      young of different ages varies considerably. This study investigates relaxin
      receptor (LGR7) expression in different mammary glands and nipples during early
      lactation in the wallaby. LGR7s were upregulated in the nipple and mammary gland
      supporting the neonate 5-11 d postpartum. LGR7 mRNA concentrations were also
      significantly higher in the gland supporting the newborn young than the older
      young. These data suggest that a local stimulus, that is, continuous sucking by
      the neonate, may influence LGR7 expression in the mammary apparatus.

PMID- 15956693
TI  - Relaxin regulates endometrial structure and function in the rhesus monkey.
AB  - The actions of relaxin are highly species specific. The role of relaxin in human
      endometrial function has not been well understood because of the paucity of in
      vivo studies in women or in suitable primate models. A model of early human
      pregnancy was established in ovariectomized, steroid-primed rhesus monkeys.
      Relaxin exerts dramatic uterine effects in this model, including a pronounced
      increase in uterine weight and stimulation of endometrial angiogenesis. In
      addition, relaxin negatively regulates expression of endometrial matrix
      metalloproteinases (MMP), causing decreased endometrial levels of MMP-1 and MMP-3
      proteins and increased protein levels of their endogenous inhibitor, tissue
      inhibitor of metalloproteinase 1. This results in maintenance of endometrial
      collagen content. The negative effects of relaxin on MMP expression in the
      endometrium are in distinct contrast to the positive regulation of MMPs
      previously shown in fibroblasts from other tissues including the cervix. Relaxin
      also significantly inhibits endometrial levels of estrogen receptor alpha and
      significantly inhibits levels of progesterone isoforms B and A. The findings that
      relaxin stimulates new blood vessel formation while maintaining endometrial
      connective tissue integrity are consistent with a significant role of relaxin in
      the establishment and/or maintenance of early pregnancy.

PMID- 15956695
TI  - Potential binding sites for relaxin in pregnant rabbits.
AB  - The purpose of this study was to identify tissues in the day 25 pregnant rabbit
      that bind relaxin. First, the clearance half-life of relaxin from the rabbit (n =
      6) was determined by injecting 10 g porcine relaxin via the marginal ear vein.
      One-milliliter blood samples were collected via a cannula in the central ear
      artery. Samples were collected at 10- and 5-min pre-relaxin and at 1-min
      intervals post-relaxin injection, and the relaxin concentrations determined by
      radioimmunoassay. The clearance half-life was 4 min. Next, pregnant rabbits were
      infused with [125I]-relaxin. Control rabbits (n = 3) received 10 g radio-inert
      relaxin via the marginal ear vein in order to saturate endogenous receptors. Ten
      minutes later, 10 ng [125I]-relaxin was similarly injected. Treated rabbits (n =
      3) received only [125I]-relaxin. After allowing sufficient time for clearance (24
      min), a 1-mL blood sample was removed via the central ear vein. Rabbits were
      euthanized, tissues of maternal and fetal origin excised, and cpm/mg of tissue
      divided by cpm/mL of blood was determined. Differences in uptake of [125I]
      relaxin between control and treated animals, using the Student paired t test,
      were found for the uterus (P < .05), uterine cervix (P < .03), and mammary gland
      (P < .05). These data suggest potential rabbit tissues with the LGR-7 receptor.

PMID- 15956696
TI  - Porcine and human relaxin bioactivity: bioactivities of porcine relaxin and human
      relaxin do not differ in mice and rats.
AB  - This study compares the bioactivity of porcine relaxin-1 to that of recombinant
      human relaxin-2 in mice and rats. The effects of the two hormone preparations on
      elongation of the mouse interpubic ligament and both the wet weight and the
      extensibility of the rat cervix were compared. No difference in bioactivity was
      detected between porcine relaxin-1 and recombinant human relaxin-2 in either
      rodent. Therefore, decisions concerning which of the two available forms of
      relaxin to employ for in vivo experimentation in mice and rats can be made
      without concerns about relative bioactivity.

PMID- 15956697
TI  - Tissue-specific effects of relaxin on the reproductive tract of neonatal gilts.
AB  - In the pig, relaxin treatment for 2 d from birth (postnatal day 0, PND 0) was not
      uterotrophic, but it increased cervical size. To understand the mechanism
      underlying this tissue-specific response, relaxin receptor (LGR7) expression in
      the neonatal uterus and cervix was investigated. At PND 2, quantitative RT-PCR
      analysis showed that LGR7 levels were higher in the cervix than in the uterus.
      Interestingly, relaxin decreased cervical LGR7 expression when compared to that
      of the controls. Differential expression of LGR7 between uterine and cervical
      tissues may contribute to tissue-specific relaxin responsiveness in the neonatal
      porcine reproductive tract.

PMID- 15956698
TI  - Increased expression of the relaxin receptor (LGR7) in human endometrium during
      the secretory phase of the menstrual cycle.
AB  - This study investigated localization and expression of relaxin and its receptor,
      LGR7, in the human endometrium during the proliferative and secretory phases of
      the menstrual cycle. H2 relaxin binding was identified in endometrium, but not
      myometrium, and particularly in the epithelium of the endometrial glands and
      uterine lumen. Binding sites increased in the early secretory phase of the
      menstrual cycle and were paralleled by similar increases in LGR7 mRNA measured by
      Q-PCR. The increase in LGR7 expression and H2 relaxin binding in the secretory
      phase of the menstrual cycle suggests a specific role for relaxin after ovulation
      in the human uterus.

PMID- 15956699
TI  - Relaxin-induced angiogenesis in ovary contributes to follicle development.
AB  - CD31-positive blood vessels increased in human ovarian cortical tissues cultured
      with relaxin than in tissues cultured without relaxin. The number of vWF-positive
      vessels counted in rat ovaries after relaxin injection (40.5 +/- 4.3)
      significantly increased compared to that in saline-injected rats (24.3 +/- 3.0).
      The proportion of primordial follicles was significantly decreased, that of
      primary follicles was significantly increased at 16 h, and that of early antral
      follicles was significantly increased at 24 h in rats after relaxin injection.
      These results suggest that relaxin may contribute to follicle development through
      the mechanism of angiogenesis in the ovary.

PMID- 15956700
TI  - Role of relaxin in maternal renal vasodilation of pregnancy.
AB  - The remarkable hemodynamic changes of normal pregnancy are briefly reviewed. In
      addition, new findings and current concepts related to the underlying hormonal
      and molecular mechanisms are presented. Finally, work that is in progress as well
      as future directions is briefly discussed.

PMID- 15956701
TI  - Recombinant human relaxin (rhRLX) modifies systemic arterial properties in
      conscious rats irrespective of gender, but in a biphasic fashion.
AB  - Chronic administration of recombinant human relaxin (rhRLX) to conscious female
      nonpregnant rats that reaches serum concentrations of 10-30 ng/mL increases
      cardiac output and reduces systemic arterial load comparable to levels observed
      in midterm pregnancy. Chronic administration of the hormone to male rats
      increases cardiac output and reduces systemic arterial load to a similar extent.
      Short-term or chronic administration of rhRLX to conscious female rats that
      reaches serum concentrations of approximately 80 ng/mL results in minimal and
      insignificant changes. We conclude that: (1) rhRLX increases cardiac output and
      reduces arterial load irrespective of gender, and (2)the rhRLX dose response is
      biphasic.

PMID- 15956702
TI  - Renal hemodynamic effects of relaxin in humans.
AB  - Rat studies have convincingly demonstrated the essential role of the ovarian
      hormone relaxin in mediating gestational renal hemodynamic and osmoregulatory
      changes in that species. We describe a model in nonpregnant volunteers using
      exogenous hCG to stimulate the production and release of ovarian relaxin in order
      to assess renal hemodynamic responses. Women (n = 10) were serially studied +/-
      hCG stimulation during menstrual cycles with measurement of inulin, PAH, and
      neutral dextran clearances (to determine glomerular filtration rate [GFR], renal
      plasma flow [RPF], and glomerular porosity, respectively). Controls were women
      without ovarian function (n = 6) and men (n = 10). GFR and RPF were increased in
      the luteal phase compared to the follicular phase (15.3% increase in GFR, P <
      0.005; 17.8% increase in RPF, P < 0.05). In controls, GFR and RPF were not
      significantly different between study occasions. Although exogenous hCG did not
      stimulate relaxin secretion in women without ovarian function or in men, it did
      so in normal women, but not into the pregnancy range. In no group were renal
      hemodynamics augmented by administered hCG. In naturally occurring cycles,
      increased serum relaxin is associated with augmented renal hemodynamics. As
      luteal stimulation with hCG failed to yield pregnancy relaxin levels, the use of
      exogenous relaxin for human administration is needed to further elucidate the
      renal vasodilatory properties of relaxin.

PMID- 15956703
TI  - The relaxin gene-knockout mouse: a model of progressive fibrosis.
AB  - Relaxin is well known for its actions on collagen remodeling. To improve our
      understanding of the physiologic role(s) of relaxin, the relaxin gene-knockout
      (RLX-KO) mouse was established by our group and subsequently phenotyped. Pregnant
      RLX-KO mice underwent inadequate development of the pubic symphysis as well as
      the mammary glands and nipples compared to wild-type mice, thus preventing
      lactation. Later studies showed that these deficiencies were associated with
      increased collagen, primarily in the nipple and vagina. Analysis of male RLX-KO
      mice also demonstrated inadequate reproductive tract development. The testis,
      epididymis, and prostate of RLX-KO mice showed delayed tissue maturation and
      growth associated with increased collagen deposition. In nonreproductive tissues,
      an age-related increase in interstitial collagen (fibrosis) was also detected in
      the lung, heart, and kidneys of RLX-KO mice and was associated with organ
      dysfunction. From 6-9 months of age and onwards, all organs of RLX-KO mice,
      particularly male mice, underwent progressive increases in tissue weight and
      collagen content (all P < .05) compared with wild-type animals. The increased
      fibrosis contributed to bronchiole epithelium thickening and alveolar congestion
      (lung), atrial hypertrophy and increased ventricular chamber stiffness (heart) in
      addition to glomerulosclerosis (kidney). Treatment of RLX-KO mice with
      recombinant human relaxin in early and developed stages of fibrosis caused the
      reversal of collagen deposition in the lung, heart, and kidneys. Together, these
      findings suggest that relaxin is a naturally occurring inhibitor of collagen
      deposition during normal development, aging, and pregnancy and can be used to
      prevent the progression of fibrosis.

PMID- 15956704
TI  - Relaxin regulates collagen overproduction associated with experimental
      progressive renal fibrosis.
AB  - Progressive fibrosis due to excess extracellular matrix (primarily collagen) is
      the final common pathway in all forms of chronic renal disease, regardless of
      etiology, and leads to tissue dysfunction, when normal tissue is replaced by scar
      tissue. Emerging work from ourselves and others suggests that the naturally
      occurring hormone relaxin has the potential to limit renal collagen production
      and reorganization, while increasing its degradation. The outlined studies
      demonstrate relaxin's potential as an antifibrotic agent against experimental
      progressive renal disease.

PMID- 15956705
TI  - Relaxin receptor expression in hepatic stellate cells and in cirrhotic rat liver
      tissue.
AB  - Relaxin has antifibrotic effects on the hepatic stellate cells (HSCs) responsible
      for collagen deposition in cirrhosis. The expression of relaxin receptors LGR7
      and LGR8 in HSCs and liver disease was examined. Activated and quiescent HSCs
      expressed LGR7, whereas only activated HSCs expressed LGR8. Relaxin, relaxin-3,
      or InsL3 treatment increased cAMP, suggesting activation of both receptors. LGR8
      and LGR7 were present in cirrhotic rat liver, but were undetectable in normal
      liver. In conclusion, both LGR7 and LGR8 are expressed in activated HSCs and
      cirrhotic liver, suggesting that relaxin, InsL3, or relaxin-3 may be useful in
      the treatment of hepatic fibrosis.

PMID- 15956706
TI  - Relaxin modulates fibroblast function, collagen production, and matrix
      metalloproteinase-2 expression by cardiac fibroblasts.
AB  - Cardiac fibrosis is a hallmark of heart disease and involves recruitment,
      proliferation, and differentiation of extracellular matrix-producing fibroblasts,
      leading to overproduction of collagen within the myocardium. In this study, the
      effects of relaxin in inhibiting these processes were investigated. We used
      neonatal rat atrial and ventricular fibroblasts, which respond to pro-fibrotic
      stimuli (i.e., transforming growth factor-beta and angiotensin II) and naturally
      express the relaxin receptor LGR7. Relaxin significantly inhibited TGF-beta- and
      angiotensin II-mediated fibroblast function and collagen production over a 72-h
      period, while increasing MMP-2 expression and activity in the presence of both
      profibrotic factors (all P < .05). These studies demonstrate that relaxin may
      have therapeutic potential in diseased states characterized by cardiac fibrosis.

PMID- 15956707
TI  - Investigating the role of relaxin in the regulation of airway fibrosis in animal
      models of acute and chronic allergic airway disease.
AB  - Airway remodeling is a characteristic feature of asthma that leads to chronic
      irreversible airway obstruction. Fibrosis in the basement membrane region is a
      hallmark of remodeling in asthma that is not found in other diseases. In the
      outlined studies, we investigated the relationship between relaxin and airway
      fibrosis in asthma using acute and chronic models of allergic airway disease.
      These studies confirm a critical role for relaxin, in the regulation of collagen
      deposition in the airway/lung in animal models of allergic airway disease.

PMID- 15956708
TI  - Localization of LGR7 gene expression in adult mouse brain using LGR7 knock
      out/LacZ knock-in mice: correlation with LGR7 mRNA distribution.
AB  - Knowledge of the distribution of the relaxin receptor, LGR7, in the brain
      provides a basis for studies of the physiologic actions of relaxin. LGR7 knock
      out (KO) mice were produced by the in-frame replacement of LGR7 exon 10 and 11
      with a LacZ-reporter cassette (knock-in [KI]), and in this study we used LGR7
      KO/LacZ-KI mice to determine the regional/cellular distribution of LGR7 gene
      expression in adult mouse brain by assessing beta-galactosidase activity in
      perfusion-fixed sections. High densities of beta-galactosidase-positive neurons
      were detected in anterior olfactory and claustrum/endopiriform nuclei, deep
      layers of cortex (particularly somatosensory), and the subiculum. Low to moderate
      densities were detected in olfactory bulb (periglomerular layer), cingulate
      cortex, subfornical organ, hippocampal CA2/dentate hilus, amygdala, hypothalamus,
      and thalamus. This LGR7/LacZ expression appears to recapitulate that of native
      LGR7 in wild-type mice and provides a model to further investigate the phenotype
      of LGR7-responsive neurons in the brain and to help reveal functions associated
      with central relaxin signaling.

PMID- 15956709
TI  - Localization of LGR7 (relaxin receptor) mRNA and protein in rat forebrain:
      correlation with relaxin binding site distribution.
AB  - Discrete neuronal populations in brain express relaxin and relaxin-3, and
      molecular studies have identified former-orphan, G-protein-coupled receptors LGR7
      and GPCR135 as their native receptors. To better understand the role of central
      relaxin systems, we began to assess the anatomic distribution of these receptors
      and ligands in brain. This study documents the widespread distribution of LGR7
      mRNA and LGR7-like immunoreactivity (LI) throughout adult rat forebrain areas
      shown to contain specific [33P]-relaxin binding sites. High densities of LGR7
      mRNA hybridization were detected in deep layers of neocortex, hypothalamic
      paraventricular and supraoptic nuclei and within hippocampal subiculum and CA3,
      the basolateral amygdala and subfornical organ. Low to moderate hybridization was
      detected in septum, midline thalamic nuclei, arcuate and supramammillary nuclei,
      and regions of the midbrain pons. Complementary expression of LGR7-LI was
      observed in cortical pyramidal neurons, hypothalamic magnocellular neurons, and
      hippocampal pyramidal and interneurons. These findings provide further evidence
      for actions of relaxin as a modulator in somatosensory, autonomic, and
      neuroendocrine pathways.

PMID- 15956710
TI  - Insulin-relaxin family peptide signaling and receptors in mouse brain membranes
      and neuronal cells.
AB  - Several orphan G-protein-coupled receptors (GPCRs), LGR7 and LGR8, GPCR135 and
      GPCR142, were recently identified as putative, native receptors for different
      relaxin-family peptides, and their cell signaling mechanisms were elucidated in
      stably transfected cell lines. Anatomic studies have demonstrated that discrete
      populations of neurons in rat brain express relaxin and relaxin-3 mRNA/peptide,
      relaxin and relaxin-3 binding sites, and LGR7 and GPCR135 mRNAs. Thus, we began
      to assess the ability of relaxin-family peptides to alter cAMP production in
      brain and the involvement of the different native receptors. In mouse cortical
      membranes, a fixed concentration of relaxin peptides (100 nM) inhibited forskolin
      induced cAMP production, but further studies in normal and receptor knockout
      mouse strains are required to assess the specificity of these effects. In
      addition, whole-cell signaling mechanisms are being investigated in a mouse
      hypothalamic cell line, GT1-7. Such studies will help to establish the actions of
      relaxin-family peptides via their different GPCRs in different brain pathways.

PMID- 15956711
TI  - Central effects of long-term relaxin expression in the rat.
AB  - A recombinant adenovirus containing the human H2 preprorelaxin (hH2) cDNA and a
      reporter gene was coinjected with a transactivator virus (Ad-tTA) into the
      lateral cerebral ventricles of female rats. Cardiovascular effects were measured
      over a 21-day period. Circulating vasopressin in the periphery was significantly
      greater (P < .0001) in the relaxin-treated group throughout the experimental
      period, compared with controls. There was a significant decrease in plasma
      osmolality (P < .05) by approximately 10 mmol/L in the treated group by day 14.
      Immunofluorescence for hH2 present in cryosections showed rAd transduction and
      hH2 expression from ependymal cells of the ventricular system. Adenovirus
      mediated delivery of hH2 to the brain is capable of producing bioactive relaxin
      that affects cardiovascular parameters.

PMID- 15956712
TI  - Relaxin pretreatment decreases infarct size in male rats after middle cerebral
      artery occlusion.
AB  - We studied the possible neuroprotective action of relaxin in a rat stroke model.
      Relaxin (10 ng in 200 nL saline) or saline was injected into the secondary
      somatosensory cortex of anesthetized rats. Thirty minutes after treatment, the
      right middle cerebral artery was occluded, causing ischemic conditions. Brains
      were removed 4 hours after stroke, and 1-mm coronal sections were stained using 2
      3-5-triphenoltetrazolium chloride. Digital photographs were taken of the
      sections, and the ratio of infarct area to ipsilateral hemispheric area was
      calculated. Relaxin treatment significantly (P < .05) reduced this ratio compared
      with that of saline-treated controls. Results suggest that relaxin may prevent
      ischemia-induced cell death.

PMID- 15956713
TI  - Relaxin inhibits central angiotensin II expression in killifish: a central
      osmoregulatory role for relaxin and angiotensin II in the killifish Fundulus
      heteroclitus.
AB  - We investigated whether relaxin and brain angiotensin II (AII) are osmoregulatory
      hormones in killifish. Four groups of killifish acclimatized to different saline
      environments (freshwater, 25% sea water, 50% sea water [brackish], and sea water)
      were euthanized and their brains were embedded in paraffin. A separate group of
      brackish water killifish were injected with relaxin 1 h before dissection and
      embedding. Serial sagittal sections were immunohistochemically stained for AII.
      Angiotensin II immunostaining did not differ between saline environments.
      Contrary to expectation, relaxin decreased the number of AII-immunoreactive cells
      in hypothalami of brackish water fish.

PMID- 15956714
TI  - New insight into the transcriptional regulation of vascular endothelial growth
      factor expression in the endometrium by estrogen and relaxin.
AB  - Increased uterine capillary permeability, which can be induced by both estrogen
      and relaxin, is required for endometrial growth and implantation. This effect is
      mediated in both cases by estrogen receptors (ERs), via stimulation of vascular
      endothelial growth factor (VEGF) expression. The sites on the VEGF promoter
      through which induction occurs, however, are completely unclear. We have used the
      technique of chromatin immunoprecipitation in vivo to localize the site of ER
      action and identify other transcription factors that are involved. We have found
      that ERa associates with Sp1/Sp3 at a GC-rich region of the promoter. More
      interesting, however, is the observation that estrogen also induces rapid,
      transient binding of hypoxia-inducible factor 1 (HIF-1), which mediates VEGF
      transcription in response to hypoxia, to the promoter. The estrogen-induced HIF-1
      binding closely matches the estrogen-induced pattern of VEGF expression in the
      uterus, suggesting that HIF-1 is involved in that induction, and probably that of
      many other genes as well (HIF-1 is now known to regulate the expression of more
      than 40 genes). It is likely that studies now under way will also link relaxin
      induced VEGF expression to HIF-1. This is based on the similarities in the
      effects of the two hormones on VEGF expression and on their shared ability to
      activate the PI3K and MAPK pathways, both of which can activate HIF-1.

PMID- 15956715
TI  - Effects of relaxin on neonatal porcine uterine growth and development.
AB  - Relaxin (RLX), a key reproductive hormone in pigs, stimulates uterine growth in
      pregnant and prepubertal gilts and in neonates 2 weeks after birth. The neonatal
      uterotrophic response to RLX is developmentally regulated and estrogen receptor
      dependent because RLX fails to increase uterine weight in the absence of estrogen
      receptor (ER)-alpha or when the ER is chemically inactivated. However, the role
      of RLX and insulin-like peptide-3 receptors, LGR7 and LGR8, respectively, in the
      neonatal uterotrophic response is unknown. Current studies focus on direct
      (LGR7/8-mediated) and indirect (ER-mediated) effects of RLX in the neonatal
      porcine uterus. Porcine LGR7 and LGR8 cDNAs were cloned and used as probes to
      identify uterine transcripts for LGR7 and LGR8, which increased from birth
      (postnatal day [PND] 0) to PND 14, a critical period for porcine uterine
      development. In situ hybridization showed that endometrial signals for both LGR7
      and LGR8 are predominantly stromal during this period. Administration of RLX on
      PND 0, before onset of uterine ER expression, increased uterine luminal
      epithelial height (P < .05) but not uterine weight in the LGR7/8-positive uterus
      on PND 2. However, RLX increased both uterine weight and luminal epithelial
      height by PND 14 (P < .05), after overt endometrial ER expression. Aberrant ER
      activation between PND 0 and 14 alters the uterine organizational program and
      affects the function of adult porcine uterine tissues. Present data suggest that
      crosstalk between LGR7/8 and ER may be involved in estrogen-sensitive
      morphoregulatory events that are central to the development of an optimally
      functional adult uterus in the pig.

PMID- 15956716
TI  - The pregnancy hormone relaxin binds to and activates the human glucocorticoid
      receptor.
AB  - The insulin-like peptide relaxin is a central hormone of pregnancy, but it also
      produces antifibrotic, myocardial, renal, central nervous, and vascular effects.
      Recently, two G-protein-coupled receptors, LGR7 and LGR8, were identified as
      relaxin receptors. Prompted by reports on the immunoregulatory effects of
      relaxin, we investigated possible interactions with the human glucocorticoid
      receptor (GR). Relaxin blunted the endotoxin-induced production of inflammatory
      cytokines (interleukin 1 [IL-1], IL-6, and tumor necrosis factor- alpha) by human
      macrophages, an effect that was suppressed by the GR antagonist RU-486. In three
      different cell lines, relaxin induced GR activation, nuclear translocation, and
      DNA binding as assessed in glucocorticoid response element (GRE)-luciferase
      assays. Coimmunoprecipitation experiments revealed physical interaction of
      endogenous and exogenous relaxin with cytoplasmic and nuclear GR. Relaxin
      competed with GR agonists for GR binding both in vivo, in whole-cell assays, and
      in vitro, in fluorescence polarization assays. In LGR7- and LGR8-free cells, the
      relaxin-mediated activation of GR was preserved. In conclusion, relaxin acts as a
      GR agonist, a pathway pivotal to relaxin's effects on cytokine secretion by human
      macrophages. These findings may deepen our understanding of relaxin's many
      physiologic actions as well as our insights into general principles of hormone
      signaling.

PMID- 15956718
TI  - Relaxin signaling from natural receptors.
AB  - The heterodimeric peptide hormone relaxin in most cells appears to signal through
      a G-protein-coupled receptor, LGR7. Whereas in artificial cell systems, made by
      transfection of receptor-expressing gene constructs into cells normally not
      presenting the receptor, classic activation of adenylate cyclase appears to be
      mediated by Gs, in cells naturally expressing the receptor, this type of coupling
      appears to be very weak. Instead, there is good evidence of other intermediate
      steps involving cytoplasmic components and tyrosine kinase activity. Part of the
      complexity of relaxin signaling is also manifest in the variable time course of
      cAMP production evident in the THP-1 cell line, which appears to depend on
      passage number and, hence, presumably on differentiation status. It is therefore
      important to distinguish between immediate early effects, short to mid-term
      responses, and long-term responses likely the consequences of specific gene
      upregulation.

PMID- 15956717
TI  - Relaxin stimulates multiple signaling pathways: activation of cAMP, PI3K, and
      PKCzeta in THP-1 cells.
AB  - Relaxin has been shown previously to stimulate cyclic AMP production and the
      activation of MAPK. We reported that phosphoinositide-3 kinase (PI3K) activity is
      required for biphasic stimulation of cAMP by relaxin and that relaxin treatment
      increased PI3K activity in THP-1 cells. A downstream target of PI3K is protein
      kinase C zeta (PKCzeta). Relaxin stimulated translocation of PKCzeta to the
      plasma membrane in THP-1, MCF-7, pregnant human myometrial (PHM1-31), and mouse
      mesangial (MMC) cells. PKCzeta translocation is PI3K dependent and independent of
      cAMP production. Pharmacological and antisense approaches, utilized to inhibit or
      knock down PKCzeta, resulted in a 40% inhibition of relaxin-stimulated cAMP
      production. The stimulation of PKCzeta by relaxin therefore is downstream of PI3K
      leading to increased cAMP production. To determine the role of PI3K/PKCzeta
      stimulation by relaxin on downstream-mediated events, we examined the increase in
      vascular endothelial growth factor (VEGF) gene expression by relaxin. Treatment
      of THP-1 or MMC cells with the PI3K inhibitor, LY294002, abolished the relaxin
      mediated stimulation of VEGF transcript levels. In summary, relaxin has
      pleiotropic signaling effects in THP-1 cells activating ERK1/2, cAMP, PI3K, and
      PKCzeta. We have described a novel bifurcated pathway by which relaxin stimulates
      Gs alpha and PI3K/PKCzeta leading to increased cAMP production and increased VEGF
      gene expression. Some, but not all, of these pathways are detected in other cell
      lines which may cause the unique diversity of downstream responses from this
      interesting hormone.

PMID- 15956719
TI  - Signal switching after stimulation of LGR7 receptors by human relaxin 2.
AB  - Previous studies have described a biphasic cAMP response after stimulation of
      LGR7 by human gene 2 (H2) relaxin, involving both adenylate cyclase and PI3
      kinase activity. The current study identifies the upstream involvement of Gi in
      the PI3-kinase-mediated response, likely the result of receptor signal switching.
      Amino acid sequence analysis of the LGR7 C-terminal tail and intracellular loops
      revealed multiple putative phosphorylation sites, suggesting that signal
      switching from Gs to Gi may occur after receptor phosphorylation. This study
      supports a time-dependent biphasic cAMP response: an initial short Gs-adenylate
      cyclase-mediated cAMP response is followed by receptor signal switching to a Gi
      PI3-kinase-mediated response.

PMID- 15956720
TI  - Signaling pathways of the LGR7 and LGR8 receptors determined by reporter genes.
AB  - Although much is known about the pleiotropic effects mediated by relaxin, the
      exact signaling pathways involved remain relatively elusive. This study examines
      LGR7 and LGR8 signaling using reporter gene technology. The greatest response was
      observed at the CRE reporter (indicates activation of cAMP-PKA and p38/JNK
      pathways), although INSL3 treatment of LGR8 produced a lower response than H2
      relaxin treatment of LGR7. AP1 (which indicates activation of JNK pathways) was
      stimulated to a lesser degree. Three other reporters produced no response. The
      reporter gene studies suggest that ligand stimulation of LGR7 and LGR8 involves
      cAMP-PKA and p38/JNK signaling.

PMID- 15956721
TI  - Relaxin stimulates cAMP production in MCF-7 cells upon overexpression of type V
      adenylyl cyclase.
AB  - Relaxin stimulates cAMP production and activation of ERK and PI3K in THP-1 cells.
      Relaxin also stimulates protein kinase C zeta (PKCzeta) translocation to the
      plasma membrane in a PI3K-dependent manner in THP-1 and MCF-7 cells. However,
      relaxin did not increase cAMP production in MCF-7 cells. We overexpressed
      different adenylyl cyclase (AC) isoforms in MCF-7 cells to examine coupling of
      endogenous relaxin receptors to cAMP production. Overexpression of types II and
      IV AC had no effect on cAMP production by relaxin. However, overexpression of
      type V AC, which is activated by PKCzeta, showed synergistic stimulation of cAMP
      by relaxin and forskolin.

PMID- 15956722
TI  - Pathways used by relaxin to regulate myometrial phospholipase C.
AB  - Relaxin exhibits pleiotropic effects on reproductive and nonreproductive tissues;
      the signaling mechanisms underlying these functions are still not well
      understood. Activation of protein kinase A and several other signal-regulated
      protein kinases results in the phosphorylation of phospholipase C (PLC)-beta3 and
      inhibit Galpha(q)-stimulated PLC activity. Therefore, PLCbeta3 may be targeted by
      both contractant and relaxant signaling pathways in myometrium and play a
      critical role in the balance between them. PHM1 cells express mRNA for relaxin
      receptor LGR7, and relaxin inhibits oxytocin-stimulated PLC activity in these
      cells. Thus, this model system may be useful in delineating signaling pathways
      used by relaxin. Here, we present evidence that relaxin stimulates
      phosphorylation of PLCbeta3 in PHM1 cells.

PMID- 15956723
TI  - A novel, adenylate cyclase, signaling mechanism of relaxin H2 action.
AB  - For the first time, the adenylate cyclase signaling mechanism (ACSM) of the
      action of relaxin H2 was revealed and deciphered in human and rat muscle tissues.
      The comparative study of signaling blocks forming the ACSM of relaxin and insulin
      (discovered earlier) showed that the postreceptor signaling chain of relaxin
      coincides with that of insulin. However, the type of relaxin receptor involved in
      ACSM remains obscure. Currently, the ACSM of relaxin may be represented as a
      signaling cascade: receptor --> Gi protein (betagamma-dimer) -->
      phosphatidylinositol 3-kinase (PI3K) --> protein kinase Czeta (PKCzeta) --> Gs
      protein --> adenylate cyclase.

PMID- 15956724
TI  - Relaxin restores altered ileal spontaneous contractions in dystrophic (mdx) mice.
AB  - We studied the effects of relaxin on ileal contractility in normal and dystrophic
      (mdx) mice. Ileal preparations from male normal and mdx mice showed spontaneous
      myogenic contractions whose amplitude was significantly higher in the latter
      ones. Relaxin added to the bath medium together with l-arginine depressed the
      amplitude of the spontaneous contractions in the mdx mice to a level similar to
      that of the normal mice. The nitric oxide synthase (NOS) inhibitor L-N(G)
      nitroarginine reverted this effect. In mdx mice pretreated for 18 hours with
      relaxin, spontaneous motility was greatly reduced in amplitude, resembling that
      of the normal mice. Concurrently, iNOS expression in the muscle coat was markedly
      increased. Therefore, in mdx mice, relaxin can restore an ileal motility pattern
      similar to that of the normal mice by upregulating endogenous NO biosynthesis.

PMID- 15956725
TI  - Effects of relaxin on vascular smooth muscle and endothelial cells in
      normotensive and hypertensive rats.
AB  - We tested the effects of relaxin on [Ca2+]i response to angiotensin II in smooth
      muscle (vSMC) and endothelial cells isolated from hypertensive (SHR) and
      normotensive (WKY) rats. Relaxin markedly reduced the [Ca2+]i response of vSMCs
      from WKY, but not from SHR rats. Western blots showed that cGMP-dependent protein
      kinase G was reduced in vSMCs from SHR as compared with WKY rats. Relaxin also
      blunted the [Ca2+]i response in endothelial cells from WKY, but not from SHR
      rats. However, in endothelial cells from SHR and WKY rats, protein kinase G was
      nearly unexpressed, thus accounting for an alternative pathway of the
      intracellular response to nitric oxide and relaxin. Hence, vSMCs and endothelial
      cells in SHR rats show a deficiency response to nitric oxide that may render them
      insensitive to relaxin.

PMID- 15956726
TI  - Relaxin induces matrix metalloproteinase-9 through activation of nuclear factor
      kappa B in human THP-1 cells.
AB  - Matrix metalloproteinase (MMP) and relaxin are important for tissue remodeling
      and wound repair. Macrophages populate wound sites and secrete MMPs. Nuclear
      factor kappa B (NF-kappaB) is linked to MMP gene regulation. Thus, a
      monocyte/macrophage cell line, THP-1, was used to study the mechanism of
      relaxin's action on MMPs. Relaxin increased MMP-9 protein and activity in THP-1
      cell-conditioned media, with no significant change in MMP-2 activity. NF-kappaB
      DNA binding activity was elevated in response to relaxin, and supershift assay
      showed activation of both NF-kappaB subunits p50 and p65. Relaxin also reduced NF
      kappaB inhibitor protein, IkappaB-alpha. In conclusion, these data suggest that
      relaxin-induced MMP-9 expression in THP-1 cells involves NF-kappaB activation.

PMID- 15956727
TI  - Does human relaxin-2 affect peripheral blood mononuclear cells to increase
      inflammatory mediators in pathologic bone loss?
AB  - This study was designed to test the hypothesis that relaxin stimulates bone
      resorption by regulating the production of several mediators that stimulate
      osteoclast formation. The levels of mediators were measured in response to
      differing relaxin concentrations in supernatants from peripheral blood
      mononuclear cells (PBMCs), MCF-7 breast cancer cells, and normal human
      osteoblasts. Although all cell types expressed mRNA for the relaxin receptor
      (LGR7), only PBMCs responded to relaxin at physiologic levels by increasing tumor
      necrosis factor-alpha and interleukin-1beta secretion. The findings indicate that
      PBMCs should be studied in relation to the effect of relaxin on inflammation and
      bone destruction caused by osteoclasts.

PMID- 15956728
TI  - Demonstration of upregulated H2 relaxin mRNA expression during neuroendocrine
      differentiation of LNCaP prostate cancer cells and production of biologically
      active mammalian recombinant 6 histidine-tagged H2 relaxin.
AB  - Relaxin was recently implicated as a regulator of breast and prostate cancer
      progression. We characterized upregulated H2 relaxin gene expression during
      neuroendocrine differentiation of the human prostate cancer model, LNCaP. To
      examine the impact of relaxin on host cells associated with prostatic
      adenocarcinomas, we generated recombinant 6 His-tagged relaxin (RLXH) in a
      mammalian expression system. This immunoreactive and biologically active relaxin
      preparation was used to screen a variety of cell types for cAMP responsiveness.
      Of the cell types screened, none was more responsive to RLXH than the well
      characterized monocyte/macrophage cell line THP-1.

PMID- 15956729
TI  - Is relaxin a calcium transporter/buffer?
AB  - Relaxin inhibits smooth muscle contractions by binding Ca2+ and making it
      unavailable to the contractile elements. Rat uterus sarcoplasmic reticulum (SR)
      was isolated, incubated with 45Ca in the presence and absence of porcine relaxin,
      and filtered. In the presence of relaxin, only 4% of the 45Ca was on the filter
      with the SR as compared to that measured on the filter with SR alone or in the
      presence of proteins of similar isoelectric point (cytochrome C) and size
      (insulin). A Sephadex G-25 column was equilibrated with buffer containing 45Ca,
      and 0.5 mL fractions were collected. Each fraction contained 240-250 K cpm.
      Relaxin was diluted in the buffer, added to the top of the column, and eluted. A
      peak of 45Ca (>600 K cpm) was found with the eluted relaxin. No peak of 45Ca was
      associated with cytochrome C or insulin under the same conditions. The eluted
      fractions containing 45Ca and relaxin were combined. A sample was incubated with
      rabbit anti-porcine relaxin serum and goat anti-rabbit serum and centrifuged, and
      45Ca in the pellet and supernatant was determined. Ninety-eight percent of the
      45Ca was found in the supernatant. Thus, 45Ca was not tightly bound to relaxin or
      the antibodies knocked the 45Ca off. Is relaxin a calcium transporter or buffer?

PMID- 15956730
TI  - Responses of GPCR135 to human gene 3 (H3) relaxin in CHO-K1 cells determined by
      microphysiometry.
AB  - This study examined the functional response to human relaxin 2 (H2 relaxin),
      human relaxin 3 (H3 relaxin), porcine relaxin, and human INSL3 in the cytosensor
      microphysiometer, using CHO-K1 cells stably expressing human GPCR135. CHO-K1
      cells stably expressing GPCR135 were generated by the serial dilution method and
      receptor properties were assessed. Saturation studies of [125I] H3 relaxin
      binding to GPCR135 in these cells gave a Bmax of 32.61 +/- 6.5 fmol/mg protein
      and Kd of 0.12 +/- 0.08 nM. The functional response to H3 relaxin and other
      relaxin/insulin peptides of GPCR135 expressed in CHO-K1 cells was measured in the
      cytosensor microphysiometer and analyzed using inhibitors of signal transduction
      proteins.

PMID- 15956731
TI  - Human decidual relaxin and preterm birth.
AB  - Relaxin in human pregnancy is both a systemic hormone from the corpus luteum and
      an autocrine/paracrine hormone at the maternal-fetal interface formed by the
      decidua/placenta and fetal membranes. We have focused our studies on the
      autocrine/paracrine roles of relaxin, especially in the preterm premature rupture
      of the fetal membranes, which causes 30-40% of preterm births. By using different
      techniques and different tissue collections, our laboratory has shown that
      expression of the relaxin genes and proteins in the decidua and placenta is
      increased in patients with preterm premature rupture of the fetal membranes.
      Relaxin binding and the expression of LGR7 are primarily in the chorion and
      decidua and are downregulated after spontaneous labor and delivery both at term
      and preterm. However, expression of LGR7 in the fetal membranes is significantly
      greater in all clinical situations at preterm than term, suggesting an important
      role for relaxin in these tissues at that time. The roles of the relaxin system
      in three potential causes of preterm birth are discussed: in the growth and
      proliferation of the membranes important for fetal membrane accommodation to
      fetal and placental growth, in acute infection, and in the inflammatory response
      leading to the initiation of labor.

PMID- 15956732
TI  - Mechanisms of relaxin-mediated premature birth.
AB  - In women, circulating relaxin is produced by the corpus luteum of pregnancy. The
      levels of relaxin are predominantly determined by the luteal mass, the number of
      corpora lutea present. Relaxin levels are highest after ovulation induction,
      which stimulates formation of many corpora lutea. Elevated relaxin levels in the
      first trimester of pregnancy are maintained throughout pregnancy and are linearly
      related to preterm birth. In an in vitro model of late human pregnancy cervix,
      relaxin increases MMP-1 and MMP-3 and decreases TIMP-1 levels, thus acting as a
      positive regulator of matrix metalloproteinases. In an in vivo rhesus monkey
      model of early pregnancy, relaxin decreases cervical collagen content, decreases
      cervical lumican levels, and stimulates MMP-7 levels. Early effects of relaxin in
      the uterus include increasing endometrial arteriole number and increasing the
      number of leukocytes, uterine natural killer cells, macrophages, and neutrophils.
      These cells release many cytokines which contribute to changes that stimulate and
      facilitate uterine contractility. If these changes persist in late pregnancy,
      relaxin may be a mediator of labor. Excess relaxin may produce these changes at
      an accelerated rate, causing preterm birth.

PMID- 15956733
TI  - Clinical use of relaxin to facilitate birth: reasons for investigating the
      premise.
AB  - In the United States, both medical and nonmedical factors have driven the
      cesarean section rate to over 26% of all deliveries. In addition to questions of
      increased cost associated with operative delivery, some have questioned the
      ethics of performing cesarean section for nonmedical reasons. Reduction of both
      the duration and the pain associated with vaginal delivery would likely bring
      about a decline in the rate of both medical and nonmedical cesarean sections.
      This chapter summarizes recent findings that support the premise that through its
      growth-promoting and softening effects on the cervix, short-term subcutaneous
      administration of pharmacologic amounts of relaxin to women at term holds promise
      as a means of reducing the duration and discomfort associated with delivery. Two
      recent studies conducted in pregnant rats demonstrated that the cervix is highly
      responsive to relaxin during the antepartum period and that short-term
      subcutaneous administration of the hormone to relaxin-deficient animals not only
      promotes growth and softening of the cervix, but also reduces the duration of
      labor and delivery. Moreover, recent human clinical trials examining the
      influence of 24 weeks of continuous subcutaneous administration of recombinant
      human relaxin for the treatment of scleroderma provided evidence not only that
      the human reproductive tract is responsive to relaxin, but also that the
      administration of the hormone does not cause serious adverse side effects. It is
      concluded that recent findings provide an impetus for an investigation into
      relaxin's potential for cervical remodeling and facilitating birth in women.

PMID- 15956734
TI  - Relaxin concentrations in serum and urine of endangered species: correlations
      with physiologic events and use as a marker of pregnancy.
AB  - Many mammalian species are facing extinction due to problems created by human
      encroachment, agriculture, pollution, and willful slaughter. Among those at risk
      are the Asian and African elephant, Sumatran rhinoceros, and giant panda.
      Conservation groups try to save species in the wild by preserving habitat and
      limiting animal-human conflicts, often with limited success. Another alternative
      is to preserve the extant gene pool through captive breeding as a hedge against
      extinction. Measurement of circulating reproductive hormones is impractical for
      most wildlife species; determination of urinary or fecal hormone metabolites
      provides a more viable approach. To aid breeding management, one important tool
      is the ability to diagnose and monitor pregnancy, especially in species with long
      gestations (e.g., rhinos over 15 mo and elephants over 20 mo). Unfortunately,
      measuring progestins often is not useful diagnostically, because concentrations
      are similar during at least part of the pregnancy and the nonpregnant luteal
      phase in some species (e.g., elephants, rhinoceroses, and giant pandas). As serum
      relaxin reliably distinguishes between pregnancy and pseudopregnancy in bitches,
      relaxin measurement might also provide a method for detecting a successful
      pregnancy in endangered species. Appropriate immunoassay reagents have enabled
      the estimation of relaxin concentrations in the serum of elephants and rhinos and
      the determination of pregnancy establishment and the outcome. Relaxin was also
      detected in panda serum and urine. However, the extreme variability of the time
      between observed mating and parturition and the confounding factors of delayed
      implantation, pseudopregnancy, and frequent fetal resorptions made it impossible
      to use the panda relaxin data as a specific marker of pregnancy.

PMID- 15956735
TI  - Use of relaxin in orthodontics.
AB  - BAS Medical is investigating the use of relaxin to improve ortho-dontic
      treatments. Relaxin is well known for its effects on remodeling soft tissue, and
      we believe relaxin will be clinically useful in speeding tooth movement and
      preventing relapse. We investigated the use of relaxin in preventing relapse in a
      dog model. Dog maxillary second incisors were orthodontically rotated an average
      of 42 degrees, and then relaxin was administered by gingival injection to relieve
      the rotational memory in the connective tissues. Teeth were retained for 30 days
      to allow fibers to reform. Teeth then were released and relapse was measured by a
      series of impressions. Animals receiving relaxin gingival injections (n = 8) were
      compared with placebo-treated animals (n = 8) (exhibiting high relapse) and
      gingival fiberotomies (n = 8) (low relapse). Gingival fiberotomy is a surgical
      procedure to cut the gingival connective tissues away from the tooth and has been
      shown to be effective in preventing relapse clinically and in animal models.
      There was a significant difference in relapse between the fiberotomy and the
      placebo control groups, and the relaxin-treated group had an intermediate
      response between the two groups (nonsignificant). Dose and treatment optimization
      may improve the response in future studies. To study the underlying mechanisms,
      we have localized relaxin receptors on gingival and periodontal ligament
      fibroblasts in tissue slices and cell cultures. Relaxin was found to stimulate
      collagenase production by relaxin in human gingival fibroblast cultures. Taken
      together, the data support a role for relaxin therapy to speed tooth movement and
      prevent relapse in orthodontic practice.

PMID- 15956736
TI  - Does human relaxin accelerate orthodontic tooth movement in rats?
AB  - Human relaxin was administered to young rats through either minipumps (group P)
      or subcutaneous injections (group I). Control rats received pump implants
      containing placebo (group C). Day 0 was the day of orthodontic appliance
      placement and activation to pull bilateral upper first molars forward, and day 14
      was the end time point. Cephalometric radiographs (three repeated exposures) were
      taken at 0, 3, 5, 7, 10, and 14 days. The total length of three maxillary molar
      segments and the space between the first and second molars were measured under a
      dissecting microscope postmortem. Both groups P and I showed rapid tooth movement
      at day 3. Movement slowed, but it still increased gradually in group P while
      decreasing in group I after that. Concurrent tooth lateral drifts to the buccal
      side were smaller in both groups P and I. The length and space were larger in
      both groups P and I. Thus, administration of human relaxin may accelerate the
      early stages of orthodontic tooth movement in rats.

PMID- 15956737
TI  - The use of relaxin improves healing in injured muscle.
AB  - To improve the functional recovery of injured skeletal muscle, we have focused
      our efforts on both enhancement of muscle regeneration and prevention of
      fibrosis. The polypeptide cytokine/growth factor relaxin can inhibit fibrous
      tissue formation in many tissues. As a member of the insulin-like growth factor
      family, relaxin also is a potential stimulator of muscle regeneration. In the
      current experiment, we examined the antifibrotic effect of relaxin in injured
      skeletal muscle. We also investigated if the injection of relaxin would influence
      muscle regeneration after injury. Our results demonstrate that relaxin treatment
      improved histologic and physiologic healing of muscles subjected to traumatic
      injury.

PMID- 15956738
TI  - Photonic monitoring in real time of vascular endothelial growth factor receptor 2
      gene expression under relaxin-induced conditions in a novel murine wound model.
AB  - Relaxin is known to promote vascular endothelial growth factor (VEGF) expression
      in reproductive tissue, and successful wound healing depends on good
      vascularization of wound sites, a process that relaxin may facilitate. Thus, the
      objective of this study was to evaluate the efficacy of relaxin on the
      development of vascular tissue at wound sites in a novel VEGF receptor 2-luc
      (VEGFR2-luc) transgenic mouse wound model by monitoring the rate of VEGFR2-luc
      mediated gene expression using bioluminescence and real-time imaging. To this
      end, 12 FVB/N VEGFR2-luc transgenic male mice were assigned to treatments (six
      per group): saline alone or relaxin (1 g/6 h/14 days) administered
      intraperitoneally (i.p.). On day 0, a set of full-thickness wounds (6-mm punch)
      were generated under anesthesia on the dorsal aspect of each mouse. Photonic
      emissions were recorded (5-min collection of photons) from wound sites 10 min
      after the administration of luciferin (150 mg/kg i.p.) on day 0 and on days 1, 2,
      4, 7, 9, 11, and 14 postwounding to quantify luciferase activity using an IVIS
      100 biophotonic imaging system. Animals were sacrificed (three per group) on day
      7 or 14, and wound tissue specimens were recovered for molecular and histologic
      analyses. Although photonic emission from wound sites increased (P < .001) over
      time with peak values obtained by day 7, no significant (P > .05) effect of
      relaxin treatment on VEGFR2-luc gene expression was noted at wound sites. Whereas
      measuring relaxin's effect on angiogenesis indirectly via the VEGFR2 model was
      not successful, photonic imaging provides an exciting new tool using alternative
      models (i.e., VEGF-luc mouse) to study relaxin-induced gene expression in normal
      (i.e., wound healing) or tumorigenic tissues in real time.

PMID- 15956739
TI  - Relaxin of prostatic origin might be linked to perineal hernia formation in dogs.
AB  - Perineal hernia occurs spontaneously in older male dogs after idiopathic
      weakening of the pelvic diaphragm. Hernias invariably contain cystic
      paraprostatic tissues. Castration reduces incidence and recurrence after surgical
      repair. Although cystic prostatic hypertrophy is a consistent feature in patients
      with perineal hernia, an endocrine link of the disease to steroid sex hormones
      has not been demonstrated. Employing immunohistochemistry, we found intense
      relaxin immunoreactivity in dogs with perineal hernia within the epithelia of
      hypertrophic prostates and in periprostatic tissues. The prostate of normal dogs
      exhibited similar but less intense relaxin staining. In neutered dogs with
      prostatic atrophy, relaxin immunostaining was weak or absent. Periprostatic cysts
      highly expressed relaxin precursors in the fluid phase as shown by SDS-gel
      electrophoresis. Relaxin of prostatic origin, therefore, is possibly a local
      factor in connective tissue weakening and subsequently in perineal hernia
      formation.

PMID- 15956740
TI  - Basic progress and future therapeutic perspectives of relaxin in ischemic heart
      disease.
AB  - Relaxin has been validated as a cardiotropic hormone, being produced by the heart
      and acting on specific heart receptors. Evidence is accumulating that it could
      hamper the pathophysiologic mechanisms of ischemic heart disease. Time is ripe to
      study relaxin as a cardiotropic drug, as recombinant human relaxin (hrRLX) is now
      available and previous clinical trials have shown a virtual lack of toxicity and
      adverse side effects, even at high doses. Our recent observations suggest that
      relaxin, besides being a preventative agent, may also be effective in the
      treatment of acute myocardial infarction and may be an adjuvant for precursor
      cell grafting to repair postinfarct myocardium. In a swine model of myocardial
      infarction currently used to test cardiotropic drugs due to its similarities with
      human ischemic heart disease, hrRLX, given at reperfusion upon 30 min of
      ischemia, markedly reduced serum and tissue markers of myocardial injury,
      cardiomyocyte apoptosis and leukocyte recruitment, resulting in overall
      improvement in cardiac performance compared with the controls. In in vitro mixed
      cultures of mouse skeletal myoblasts and adult rat cardiomyocytes, relaxin
      increased gap junction formation and potentiated gap junction-mediated
      intercellular exchanges and signaling between the coupled cells. In view of the
      therapeutic use of myoblast grafting for cardiac repair, relaxin could hence
      favor the electromechanical coupling of grafted myoblasts with the resident
      cardiomyocytes and facilitate their transdifferentiation towards a cardiac
      phenotype. Relaxin, therefore, shows promising therapeutic potential in
      cardiology and cardiac surgery.

PMID- 15956741
TI  - Human recombinant relaxin reduces heart injury and improves ventricular
      performance in a swine model of acute myocardial infarction.
AB  - This study shows that relaxin can be effective in the treatment of acute
      myocardial infarction. In a swine model of heart ischemia-reperfusion currently
      used to test cardiotropic drugs because of its similarities with human myocardial
      infarction, human recombinant relaxin (2.5 and 5 microg/kg body weight), given at
      reperfusion after a 30-min ischemia, markedly reduced the main serum markers of
      myocardial damage (myoglobin, CK-MB, and troponin T) and the metabolic and
      histopathologic parameters of myocardial inflammation and cardiomyocyte injury,
      resulting in overall improvement of ventricular performance (increased cardiac
      index) compared to the controls. These results provide a background for future
      clinical trials with human relaxin as adjunctive therapy to catheter-based
      coronary angioplasty in patients with acute myocardial infarction.

PMID- 15956742
TI  - Relaxin as an additional protective substance in preserving and reperfusion
      solution for liver transplantation, shown in a model of isolated perfused rat
      liver.
AB  - Reperfusion injury is a problem in organ transplantation. Relaxin causes vessel
      dilation and inhibition of platelet and mast cell activation. The study
      investigates the protective effect of relaxin on liver tissue against cell damage
      during organ preservation and reperfusion. Liver transplantation was simulated in
      a model of isolated perfused rat liver. Relaxin was applicated during reperfusion
      and/or preservation. To quantify cell damage, we examined the perfusate for
      malonyldialdehyde (MDA) and myeloperoxidase activity (MPO), and liver tissue
      underwent immunohistochemical study. Relaxin as an additional substance in
      preserving/reperfusion solution decreases MPO and MDA levels in the perfusate and
      immunohistochemical study. Relaxin seems to have a protective effect against cell
      damage in ischemia and reperfusion injury.

PMID- 15956743
TI  - Myocardial relaxin counteracts hypertrophy in hypertensive rats.
AB  - Current findings in male relaxin knockout mice indicate antifibrotic and positive
      lusitropic actions of relaxin on the myocardium. We investigated in 12-month-old
      male spontaneously hypertensive rats (SHR) and age-matched male Wistar-Kyoto rats
      (WKY) whether RLX shows antihypertrophic actions as well. SHR showed left heart
      hypertrophy and a selective elevation of left atrial and ventricular relaxin
      peptide which inversely correlated with the degree of hypertrophy. In adult rat
      cardiomyocytes, relaxin blunted phenylephrine-induced hypertrophy by inhibiting
      activated ERK-1/2 kinases. In conclusion, endogenous myocardial relaxin,
      upregulated in left heart hypertrophy, exerts antihypertrophic effects by
      inhibition of activated ERK-1/2 kinases.

PMID- 15956744
TI  - Relaxin favors the morphofunctional integration between skeletal myoblasts and
      adult cardiomyocytes in coculture.
AB  - We have investigated the interaction between mouse skeletal myoblasts and rat
      cardiomyocytes in coculture and the influence of relaxin. Connexin43 expression,
      Lucifer yellow microinjection, Ca2+ propagation, and electrophysiological
      analysis have shown that myoblasts and cardiomyocytes are coupled by functional
      gap junctions. Cardiomyocytes and relaxin upregulated connexin43 expression and
      gap junctional communication in myoblasts. Relaxin also increased transjunctional
      current between myoblasts and between myoblasts and cardiomyocytes. In
      conclusion, relaxin potentiates the intercellular coupling, upregulating the
      transcellular exchange of regulatory molecules between myoblasts and
      cardiomyocytes, including Ca2+. This could favor the transdifferentiation of
      myoblasts toward a cardiac phenotype.

PMID- 15956745
TI  - Relaxin adenylyl cyclase system of pregnant women with diabetes: functional
      defects in insulin and relaxin adenylyl cyclase signaling systems in myometrium
      of pregnant women with type 1 diabetes.
AB  - The study was conducted to reveal the functional disturbances in two novel
      insulin and relaxin adenylyl cyclase signaling mechanisms (ACSMs). It was shown
      for the first time that in myometrium of pregnant women with insulin
      insufficiency the functional defects of Gs-protein-AC coupling in insulin- and
      relaxin H2-regulated AC systems were developed. As a result, the sensitivity of
      the signaling systems to both hormones and potentiation of their AC effects by
      guanine nucleotides were markedly decreased compared with that in control group.
      These functional defects in ACSM may lead to violation of the process of insulin
      and relaxin signal transduction.

PMID- 15956746
TI  - Human medullary thyroid carcinoma: a source and potential target for relaxin-like
      hormones.
AB  - We investigated the expression of H1, H2 relaxin and INSL-3, mRNA and protein,
      and LGR7 and LGR8 transcripts in human C-cell hyperplasia, primary medullary
      thyroid carcinoma (MTC) tissues, MTC metastases, and the human MTC-TT and mouse
      MTC-M cell lines. Relaxin-like peptide hormones were detected in C-cell
      hyperplasia and in MTC tissues, but were absent in human normal parafollicular C
      cells of benign goiter tissues. In contrast to calcitonin, mRNA, and
      immunoreactive protein, no differences in the expression of relaxin and INSL3
      were observed in MTC tissues of different pTNM classification or between primary
      and metastatic MTC tissues studied. All MTC tissues constitutively expressed LGR7
      and LGR8 transcripts. Thus, relaxin-like hormones appear to be present early
      during C-cell hyperplasia and potentially functional relaxin/INSL3 ligand
      receptor systems are present in human MTC tissues and in MTC cell lines.

PMID- 15956747
TI  - Relaxin downregulates the calcium binding protein S100A4 in MDA-MB-231 human
      breast cancer cells.
AB  - Expressed in the human breast and in human breast cancer tissues, the
      heterodimeric peptide hormone relaxin is involved in extracellular matrix
      turnover. To investigate the role of relaxin in estrogen receptor-alpha negative
      human breast cancer cells, we established transfectants of the human MDA-MB-231
      breast cancer cell line stably overexpressing H2-relaxin (MDA-MB-231/pIRES-EGFP
      H2). These transfectants produced and secreted functional relaxin. Our
      investigations revealed downregulation of mRNA and protein of the calcium binding
      protein S100A4 (metastasin) in MDA-MB-231/pIRES-EGFP-H2 transfectants, indicating
      a distinct and novel role for relaxin in estrogen receptor-alpha negative human
      breast cancer cells.

PMID- 15956748
TI  - Relaxin does not influence the growth of human cervical adenocarcinoma (HeLa)
      cells in culture.
AB  - This study was performed to determine whether relaxin influences the growth of
      human adenocarcinoma (HeLa) cells of the cervix, which has been shown to contain
      relaxin-binding sites and proliferate by relaxin. Cells were maintained in
      Dulbecco's modified Eagle's medium with 5% fetal calf serum. Highly purified
      porcine relaxin was added at concentrations of 10(-11) to 10(-5) M and incubated
      for 44, 69, 94, and 118 h. Cell proliferation/cytotoxicity and endogenous nitric
      oxide production were determined using a colorimetric MTS assay and Griess assay,
      respectively. The results indicate that whereas relaxin promotes the growth rate
      of MCF-7 cells, which is in agreement with previous reports, at the doses and
      times of exposure used in this study relaxin does not significantly influence the
      number of viable HeLa cells. However, relaxin at nanomolar concentrations (10(-9)
      to 10(-8) M) promoted the growth of HeLa cells in the presence of both estrogen
      and progesterone to a small extent. In agreement with these results, relaxin did
      not affect nitric oxide production. We conclude that relaxin may have
      differential effects on the growth of two different cancer cell types, MCF-7 and
      HeLa cells.

PMID- 15956749
TI  - Effects of relaxin in a model of rat adjuvant-induced arthritis.
AB  - A reduction in the incidence and severity of rheumatoid arthritis is seen in
      pregnant women. Relaxin, a hormone of pregnancy, has been implicated in decreased
      immune responsiveness. Consequently, the effects of relaxin and estradiol
      valerate, alone or in combination, were assessed in the development of adjuvant
      induced arthritis in the rat. Combination hormone therapy reduced adjuvant
      induced paw inflammation. Radiographic analysis of the tarsal joints showed that
      estradiol valerate plus relaxin treatment minimized soft tissue damage and bone
      changes when compared to vehicle-treated arthritic controls. These results
      indicate that relaxin may be a factor in reducing inflammation during pregnancy.

PMID- 15956751
TI  - Insulin-like factor 3: a novel circulating hormone of testicular origin in
      humans.
AB  - Insulin-like factor 3 (INSL3) affects testicular descent. Mutations in the INSL3
      gene or its receptor, LGR8/GREAT, can cause cryptorchidism. Expression of
      LGR8/GREAT in different tissues and production of INSL3 by adult-type Leydig
      cells suggest additional roles for this hormonal system in adults. We used a
      novel radioimmunoassay kit to measure INSL3 concentrations in the serum of normal
      men and those with different testicular pathologies. We demonstrate that INSL3
      circulates in adult men and is almost exclusively of testicular origin. Subjects
      with severe testicular damage (infertility) produce small amounts of INSL3, and
      concentrations of this hormone seem to reflect the functional status of the
      Leydig cells. Analysis of men treated with different combinations of hormones of
      the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is
      related to the luteinizing hormone.

PMID- 15956750
TI  - Insulin-like factor 3: where are we now?
AB  - Insulin-like factor 3 (INSL3), previously known as the relaxin-like factor (RLF),
      is a major peptide hormone secreted from the testicular Leydig cells of adult men
      and circulating in the blood at a concentration of approximately 1 ng/mL. Women
      also produce INSL3 in the theca interna cells of ovarian follicles, but
      circulating levels remain below 100 pg/mL. INSL3 is structurally related to
      relaxin and insulin, but unlike the latter, signals through a novel G-protein
      coupled receptor, LGR8. Ablation of the gene for INSL3 leads primarily to
      cryptorchidism because of a defect in the first, transabdominal phase of
      testicular descent. In the adult knockout mouse, a mild phenotype is evident in
      the testis and ovary. We have developed a panel of antibodies specific for INSL3
      from various species, which are suitable for immunohistochemistry and, more
      recently, for immunoassays. INSL3 is an important marker for the mature Leydig
      cell phenotype, where it appears to be expressed constitutively, once the mature
      differentiation state is achieved. It is also an indicator of differentiation
      status not only for Leydig cells but also for the theca interna cells of the
      ovary.

PMID- 15956752
TI  - Immunohistochemical localization of relaxin-like factor/insulin-like peptide-3 in
      the bovine corpus luteum.
AB  - Relaxin-like factor/insulin-like peptide (INSL)-3 is highly expressed in the
      bovine corpus luteum throughout the estrous cycle and pregnancy. Demonstration of
      translation of the relaxin-like factor message was previously shown for the
      follicle but not the corpus luteum. In this study, relaxin-like factor mRNA was
      highly expressed in the corpus luteum on days 7 and 14 of pregnancy. Tissues were
      fixed in 10% neutral buffered formalin, and utilizing two different antibodies to
      relaxin-like factor, W3 rabbit anti-bovine and 2-8F mouse anti-bovine, relaxin
      like factor was localized in fibroblast-like cells. Staining was also observed in
      the Leydig cells of bovine testicular tissue. No staining was observed in small
      and large steroidogenic luteal cells, indicating a nonsteroidogenic source of
      luteal relaxin-like factor. Definitive cell type identification is currently
      being determined via electron microscopy.

PMID- 15956753
TI  - Restricted expression of LGR8 in intralaminar thalamic nuclei of rat brain
      suggests a role in sensorimotor systems.
AB  - LGR8 was recently identified as a cognate receptor for insulin-like peptide-3
      (INSL3), and INSL3-LGR8 signaling is best known for its role in testis descent
      during development. LGR8 mRNA has been detected in various human tissues
      including brain, but the regional and cellular distribution of LGR8 expression in
      the mammalian central nervous system is unknown. Therefore, in this study we
      investigated the presence and localization of LGR8 mRNA in rat brain using
      reverse transcription-polymerase chain reaction and in situ hybridization
      histochemistry. Results revealed a distinct distribution of LGR8 in forebrain,
      with transcripts principally restricted to the posterior thalamus and highest
      densities detected in the parafascicular nucleus of both adult and developing
      rats. Unexpectedly, INSL3 mRNA was not detected in brain by similar methods, but
      preliminary electrophysiologic studies of parafascicular neurons revealed that
      INSL3 altered their activity. These findings suggest that LGR8 signaling may be
      involved in sensorimotor control in the rat and perhaps other species,
      particularly via actions on parafascicular neurons that project to basal ganglia
      and are depleted in Parkinson's disease.

PMID- 15956754
TI  - Detection, localization, and action of the INSL3 receptor, LGR8, in rat kidney.
AB  - Recent molecular and pharmacologic studies have identified LGR8, a member of the
      leucine-rich repeat-containing G-protein-coupled receptor family, as a cognate
      receptor for insulin-like peptide-3 (INSL3). LGR8 mRNA has been detected in
      various tissues, but the precise roles of these INSL3-LGR8 systems are unknown.
      In this study we first investigated the presence and cellular localization of
      LGR8 mRNA in both adult and developing rat kidney and subsequently examined the
      possible role of INSL3-LGR8 signaling in cultured mesangial cells. LGR8 mRNA was
      detected in the kidney by polymerase chain reaction and localized by in situ
      hybridization in mature glomerular mesangial cells within the renal cortex, with
      highest levels detected at embryonic day 18 and lowest levels in adult kidney.
      Synthetic INSL3 inhibited the proliferation of mesangial cells in primary
      culture, indicating the presence of functional LGR8 on these cells. These
      findings suggest that INSL3/LGR8 signaling may be involved in the genesis and/or
      developmental maturation of renal glomeruli and in the regulation of mesangial
      cell density in the adult kidney.

PMID- 15956755
TI  - Evolution of the signaling system in relaxin-family peptides.
AB  - Recent studies have characterized two G-protein-coupled receptors (GPCRs), LGR7
      and LGR8, as relaxin receptors. Later studies have shown that LGR7 and LGR8 also
      are cognate receptors for the relaxin-family peptides, INSL7/relaxin3 and INSL3,
      respectively. In addition, INSL7/relaxin3 signals through two orphan GPCRs,
      GPCR135 and GPCR142, whereas INSL5 is a select ligand for GPCR142. These findings
      have greatly enhanced our understanding of the physiology and signaling of this
      unique group of peptide hormones. Phylogenetic analysis of relaxin-family
      peptides and their co-evolved receptors suggests that the ancestor relaxin gene
      duplicated multiple times in a vertebrate branch-specific manner. Among the seven
      human relaxin-family peptides (relaxin1, relaxin2, INSL3/RLF, INSL4/EPIL,
      INSL5/RIF2, INSL6/RIF1, and INSL7/relaxin3), INSL7 and INSL5 could represent the
      most ancient form. By contrast, the most widely studied family peptides, human
      relaxins H1 and H2, appear to be derived from recent gene duplication in mammals.
      Therefore, relaxin-family peptides could be important for the evolution and
      adaptation to lineage-specific physiologic processes during evolution. Duplicated
      relaxin-family genes assumed regulatory roles in newly evolved reproductive
      processes, and relaxin/LGR signaling was harnessed for signaling in the uterus
      and mammary gland in addition to other tissues. Although the precise evolutionary
      history of relaxin ligand/receptor pairs remains to be elucidated, these findings
      indicate that the expansion of relaxin-family genes and their specific regulatory
      functions have evolved during vertebrate evolution to allow the development of a
      tissue-specific regulatory mechanism in a lineage-specific manner and provide a
      revealing portrait of molecular evolution in action.

PMID- 15956756
TI  - Evolution of the relaxin-like peptide family: from neuropeptide to reproduction.
AB  - The relaxin-like peptide family consists of relaxin-1, relaxin-2, and relaxin-3
      and the insulin-like peptides (INSL)-3, INSL4, INSL5, and INSL6 (human relaxin-2
      is equivalent to relaxin-1 in other species). Evolution of this family has been
      contentious. We therefore sought to clarify the issue by performing phylogenetic
      analysis of all relaxin-like peptides from the genomic databases available.
      Surprisingly, the phylogeny, combined with previous biologic characterizations,
      suggest that although relaxin's original function was likely in the brain, its
      reproductive role was acquired just prior to the divergence of amphibians. This
      phylogeny also illuminates inconsistencies in relaxin evolution in invertebrates,
      chickens, and cows.

PMID- 15956757
TI  - Coevolution of the relaxin-like peptides and their receptors.
AB  - Currently, four relaxin peptide family receptors are known: LGR7 is the relaxin
      receptor, although it also interacts specifically with relaxin-3; LGR8 is the
      insulin-like factor 3 (INSL3) receptor; and GPCR135 or the somatostatin- and
      angiotensin-like peptide receptor (SALPR) and GPCR142 are both specific relaxin-3
      receptors. Because these receptors coevolved together with their relaxin ligands,
      phylogenetic analysis of these sequences can provide insight into peptide
      receptor interactions and even predict interacting partners for INSL4, INSL5, and
      INSL6, the receptors for which are unknown.

PMID- 15956759
TI  - High-soy diet decreases infarct size after permanent middle cerebral artery
      occlusion in female rats.
AB  - Estrogen is a powerful neuroprotective agent in rodent models of ischemic stroke.
      However, in humans, estrogen treatment can increase risk of stroke. Health risks
      associated with hormone replacement have led many women to consider alternative
      therapies including high-soy diets or supplements containing soy isoflavones,
      which act as estrogen receptor ligands to selectively mimic some of estrogen's
      actions. We hypothesized that a high-soy diet would share the neuroprotective
      actions of estrogen in focal cerebral ischemia. Female Sprague-Dawley rats were
      ovariectomized and divided into three groups: isoflavone-free diet + placebo (IF
      P), isoflavone-free diet + estradiol (IF-E), or high-soy diet + placebo (S-P).
      Two weeks after being placed on diets, rats underwent left permanent middle
      cerebral artery occlusion (MCAO). Reductions in ipsilateral cerebral blood flow
      were equivalent across groups ( approximately 50%). Twenty-four hours later
      neurological deficit was determined, and brains were collected for assay of
      cerebral infarct by TTC staining. In the IF-P rats MCAO produced a 50 +/- 4%
      cerebral infarct. Estrogen and high-soy diet both significantly reduced the size
      of the infarcts to 26 +/- 5% in IF-E rats and to 37 +/- 5% in S-P rats. Analysis
      at five rostro-caudal levels revealed that estrogen treatment was slightly more
      effective at reducing infarct size than high soy diet. Overall neurological
      deficit scores at 24 h correlated with infarct size; however, there were no
      statistically significant differences among the treatment groups. These data show
      that 2 wk of a high-soy diet is an effective prophylactic strategy for reducing
      stroke size in a rat model of focal cerebral ischemia.

PMID- 15956760
TI  - PKC-induced ERK1/2 interactions and downstream effectors in ovine cerebral
      arteries.
AB  - Both protein kinase C (PKC) and extracellular signal-regulated kinases (ERK1/2)
      are involved in mediating vascular smooth muscle contraction. We tested the
      hypotheses that in addition to PKC activation of ERK1/2, by negative feedback
      ERKs modulate PKC-induced contraction, and that their interactions modulate both
      thick and thin myofilament pathways. In ovine middle cerebral arteries (MCA), we
      measured isometric tension and intracellular free calcium concentration
      ([Ca(2+)](i)) responses to PKC stimulation [phorbol 12,13-dibutyrate (PDBu), 3 x
      10(-6) M] in the absence or presence of ERK1/2 inhibition (U-0126, 10(-5) M).
      After PDBu +/- ERK1/2 inhibition, we also examined by Western immunoblot the
      levels of total and phosphorylated ERK1/2, caldesmon(Ser789), myosin light
      chain(20) (MLC(20)), and CPI-17. PDBu induced significant increase in tension in
      the absence of increased [Ca(2+)](i). PDBu also increased phosphorylated ERK1/2
      levels, a response blocked by U-0126. In turn, U-0126 augmented PDBu-induced
      contractions. PDBu also was associated with significant increases in
      phosphorylated caldesmon(Ser789) and MLC(20) levels, each of which peaked at 5 to
      10 min. PDBu also increased phosphorylated CPI-17 levels, which peaked at 2 to 3
      min. Rho kinase inhibition (Y-27632, 3 x 10(-7) M) did not alter PDBu-induced
      contraction. These results support the idea that PKC activation can increase CPI
      17 phosphorylation to decrease myosin light chain phosphatase activity. In turn,
      this increases MLC(20) phosphorylation in the thick filament pathway and
      increases Ca(2+) sensitivity. In addition, ERK1/2-dependent phosphorylation of
      caldesmon(Ser789) was not necessary for PDBu-induced contraction and appears not
      to be involved in the reversal of caldesmon's inhibitory effect on actin-myosin
      ATPase.

PMID- 15956761
TI  - The melanocortin system as a central integrator of direct and indirect controls
      of food intake.

PMID- 15956762
TI  - Comments on "Do fever and anapyrexia exist? Analysis of set point-based
      definitions".

PMID- 15956763
TI  - Transcriptional reprogramming during reloading of atrophied rat soleus muscle.
AB  - The hypothesis was tested that differential, coregulated transcriptional
      adaptations of various cellular pathways would occur early with increased
      mechanical loading of atrophied skeletal muscle and relate to concurrent damage
      of muscle fibers. Atrophy and slow-to-fast fiber transformation of rat soleus
      muscle was provoked by 14 days of hindlimb suspension (HS). Subsequent reloading
      of hindlimbs caused a fourfold increase in the percentage of muscle fibers,
      demonstrating endomysial tenascin-C staining. Five days after reloading, when 10%
      of the fibers were damaged, the normal muscle weight and slow-type fiber
      percentage were reestablished. Microarray analysis revealed major, biphasic
      patterns of gene expressional alterations with reloading that distinguish between
      treatments and gene ontologies. Transcript levels of factors involved in protein
      synthesis and certain proteasomal mRNAs were increased after 1 day of reloading
      and correlated to the percentage of fibers surrounded by tenascin-C. By contrast,
      levels of gene messages for fatty acid transporters, respiratory chain
      constituents, and voltage-gated cation channels were transiently reduced after 1
      day of muscle loading and associated with the number of damaged fibers and the
      regain in muscle weight. This coregulation points toward important retooling of
      oxidative metabolism and the T- and SR-tubular systems with rebuilding of slow
      fibers. The observations demonstrate that early nuclear reprogramming with
      reloading of atrophic soleus muscle is coordinated and links to the processes
      involved in mechanical damage and regeneration of muscle fibers.

PMID- 15956764
TI  - Fetal alcohol syndrome: an assessment of the field.
AB  - Fetal exposure to alcohol is the major known cause of mental retardation in the
      Western world. For more than half of the 20th century, the placenta was widely
      believed to be an effective barrier against environmental agents. The discovery
      that offspring of pregnant women who were exposed to German measles or
      administered thalidomide were often malformed raised awareness that teratogens
      could be any environmental agent, including viruses and drugs, that caused
      abnormal development. Alcohol was not identified as a teratogen until the 1970s.
      Fetal exposure to alcohol can cause fetal alcohol syndrome (FAS), which is
      characterized by specific physical traits and central nervous system
      dysfunctions. The development of animal model systems has facilitated our study
      of the effects of fetal alcohol exposure and the elucidation of the mechanisms
      involved in alcohol-induced abnormal development. Despite our current
      understanding of the effects of fetal alcohol exposure, the occurrence of FAS and
      associated fetal alcohol spectrum disorders is still widespread and the
      associated health-care costs are staggering. This symposium provides an up-to
      date analysis of fetal exposure to alcohol and FAS. It is directed not only to
      investigators working in the field but to a diverse group of scientists working
      in the biological and biomedical fields to stimulate cross-disciplinary
      awareness, interest, and collaboration.

PMID- 15956765
TI  - Fetal alcohol spectrum disorders: an overview with emphasis on changes in brain
      and behavior.
AB  - Fetal alcohol spectrum disorders constitute a major public health problem. This
      article presents an overview of important issues that surround these disorders
      and emphasizes the structural and neurobehavioral consequences associated with
      prenatal exposure to alcohol. Diagnostic criteria are discussed, and possible
      moderating factors for the range of outcomes are mentioned. In addition, the
      prevalence of fetal alcohol spectrum disorders is described, and estimates of the
      financial impact of these disorders are given. Heavy prenatal alcohol exposure
      can severely affect the physical and neurobehavioral development of a child.
      Autopsy and brain imaging studies indicate reductions and abnormalities in
      overall brain size and shape, specifically in structures such as the cerebellum,
      basal ganglia, and corpus callosum. A wide range of neuropsychological deficits
      have been found in children prenatally exposed to alcohol, including deficits in
      visuospatial functioning, verbal and nonverbal learning, attention, and executive
      functioning. These children also exhibit a variety of behavioral problems that
      can further affect their daily functioning. Children exposed to alcohol
      prenatally, with and without the physical features of fetal alcohol syndrome,
      display qualitatively similar deficits. Determining the behavioral phenotypes
      that result from heavy prenatal alcohol exposure is critical, because the
      identification of these children is crucial for early interventions. In addition,
      knowing which brain areas are involved might enable the development of better
      intervention strategies. However, intervention needs to go beyond the affected
      individual to prevent future cases. As evidenced by the staggering financial
      impact these disorders have on society, prevention efforts need to be aimed at
      high-risk groups, and this issue needs to be made a high priority in terms of
      public health.

PMID- 15956766
TI  - Genesis of alcohol-induced craniofacial dysmorphism.
AB  - The initial diagnosis of fetal alcohol syndrome (FAS) in the United States was
      made because of the facial features common to the first cohort of patients. This
      article reviews the development of an FAS mouse model whose craniofacial features
      are remarkably similar to those of affected humans. The model is based on short
      term maternal treatment with a high dosage of ethanol at stages of pregnancy that
      are equivalent to Weeks 3 and 4 of human gestation. At these early stages of
      development, alcohol's insult to the developing face is concurrent with that to
      the brain, eyes, and inner ear. That facial and central nervous system defects
      consistent with FAS can be induced by more "realistic" alcohol dosages as
      illustrated with data from an oral alcohol intake mouse model in which maternal
      blood alcohol levels do not exceed 200 mg/dl. The ethanol-induced pathogenesis
      involves apoptosis that occurs within 12 hrs of alcohol exposure in selected cell
      populations of Day 7, 8, and 9 mouse embryos. Experimental evidence from other
      species also shows that apoptosis underlies ethanol-induced malformations. With
      knowledge of sensitive and resistant cell populations at specific developmental
      stages, studies designed to identify the basis for these differing cellular
      responses and, therefore, to determine the primary mechanisms of ethanol's
      teratogenesis are possible. For example, microarray comparisons of sensitive and
      resistant embryonic cell populations have been made, as have in situ studies of
      gene expression patterns in the populations of interest. Studies that illustrate
      agents that are effective in diminishing or exacerbating ethanol's teratogenesis
      have also been helpful in determining mechanisms. Among these agents are
      antioxidants, sonic hedgehog protein, retinoids, and the peptides SAL and NAP.

PMID- 15956767
TI  - Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and
      immune function.
AB  - Alcohol abuse is known to result in clinical abnormalities of endocrine function
      and neuroendocrine regulation. However, most studies have been conducted on
      males. Only recently have studies begun to investigate the influence of alcohol
      on endocrine function in females and, more specifically, endocrine function
      during pregnancy. Alcohol-induced endocrine imbalances may contribute to the
      etiology of fetal alcohol syndrome. Alcohol crosses the placenta and can directly
      affect developing fetal cells and tissues. Alcohol-induced changes in maternal
      endocrine function can disrupt maternal-fetal hormonal interactions and affect
      the female's ability to maintain a successful pregnancy, thus indirectly
      affecting the fetus. In this review, we focus on the adverse effects of prenatal
      alcohol exposure on neuroendocrine and immune function, with particular emphasis
      on the hypothalamic-pituitary-adrenal (HPA) axis and the concept of fetal
      programming. The HPA axis is highly susceptible to programming during fetal
      development. Early environmental experiences, including exposure to alcohol, can
      reprogram the HPA axis such that HPA tone is increased throughout life. We
      present data that demonstrate that maternal alcohol consumption increases HPA
      activity in both the maternal female and the offspring. Increased exposure to
      endogenous glucocorticoids throughout the lifespan can alter behavioral and
      physiologic responsiveness and increase vulnerability to illnesses or disorders
      later in life. Alterations in immune function may be one of the long-term
      consequences of fetal HPA programming. We discuss studies that demonstrate the
      adverse effects of alcohol on immune competence and the increased vulnerability
      of ethanol-exposed offspring to the immunosuppressive effects of stress. Fetal
      programming of HPA activity may underlie some of the long-term behavioral,
      cognitive, and immune deficits that are observed following prenatal alcohol
      exposure.

PMID- 15956768
TI  - Animal model systems for the study of alcohol teratology.
AB  - The incidence of fetal alcohol syndrome has not been declining even though
      alcohol has been established as a teratogen and significant efforts have been
      made to educate women not to abuse alcohol during pregnancy. In addition to
      further educational efforts, strategies to prevent or mitigate the damages of
      prenatal alcohol exposure are now under development. Animal models will play a
      significant role in the effort to develop these strategies. Because prenatal
      alcohol exposure causes damage by multiple mechanisms, depending on dose,
      pattern, and timing of exposure, and because no species of animal is the same as
      the human, the choice of which animal model to use is complicated. To choose the
      best animal model, it is necessary to consider the specific scientific question
      that is being addressed and which model system is best able to address the
      question. Animal models that are currently in use include nonhuman primates,
      rodents (rats, mice, guinea pigs), large animal models (pig and sheep), the
      chick, and simple animals, including fish, insects, and round worms. Each model
      system has strengths and weaknesses, depending on the question being addressed.
      Simple animal models are useful in exploring basic science questions that relate
      to molecular biology and genetics that cannot be explored in higher-order
      animals, whereas higher-order animal models are useful in studying complex
      behaviors and validating basic science findings in an animal that is more like
      the human. Substantial progress in this field will require the judicious use of
      multiple scientific approaches that use different animal model systems.

PMID- 15956769
TI  - Alcohol teratogenesis: mechanisms of damage and strategies for intervention.
AB  - There are multiple mechanisms by which alcohol can damage the developing brain,
      but the type of damage induced will depend on the amount and developmental timing
      of exposure, along with other maternal and genetic factors. This article reviews
      current perspectives on how ethanol can produce neuroteratogenic effects by its
      interactions with molecular regulators of brain development. The current evidence
      suggests that alcohol produces many of its damaging effects by exerting specific
      actions on molecules that regulate key developmental processes (e.g., L1 cell
      adhesion molecule, alcohol dehydrogenase, catalase), interfering with the early
      development of midline serotonergic neurons and disrupting their regulatory
      signaling function for other target brain structures, interfering with trophic
      factors that regulate neurogenesis and cell survival, or inducing excessive cell
      death via oxidative stress or activation of caspase-3 proteases. The current
      understanding of pathogenesis mechanisms suggests several strategic approaches to
      develop rational molecular prevention. However, the development of behavioral and
      biologic treatments for alcohol-affected children is crucial because it is
      unlikely that effective delivery of preventative interventions can realistically
      be achieved in ways to prevent prenatal damage in at-risk pregnancies. Toward
      that end, behavioral training that promotes experience-dependent neuroplasticity
      has been effective in a rat model of cerebellar damage induced by alcohol
      exposure during the period of brain development that is comparable to that of the
      human third trimester.

PMID- 15956770
TI  - General discussion at the fetal alcohol syndrome symposium.

PMID- 15956771
TI  - Propofol is cardioprotective in a clinically relevant model of normothermic blood
      cardioplegic arrest and cardiopulmonary bypass.
AB  - The general anesthetic propofol has been shown to be cardioprotective. However,
      its benefits when used in cardioplegia during cardiac surgery have not been
      demonstrated. In this study, we investigated the effects of propofol on metabolic
      stress, cardiac function, and injury in a clinically relevant model of
      normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized
      pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were
      surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest.
      Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60
      min aortic cross-clamped period. Propofol was continuously infused for the
      duration of CPB and was therefore present in blood cardioplegia. Myocardial
      biopsies were collected before, at the end of cardioplegic arrest, and 20 mins
      after the release of the aortic cross-clamp. Hemodynamic parameters were
      monitored and blood samples collected for cardiac troponin I measurements.
      Propofol infusion during CPB and before ischemia did not alter cardiac function
      or myocardial metabolism. Propofol treatment attenuated the changes in myocardial
      tissue levels of adenine nucleotides, lactate, and amino acids during ischemia
      and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced
      measurable hemodynamic dysfunction after cardioplegic arrest when compared to
      untreated controls. In conclusion, propofol protects the heart from ischemia
      reperfusion injury in a clinically relevant experimental model. Propofol may
      therefore be a useful adjunct to cardioplegic solutions as well as being an
      appropriate anesthetic for cardiac surgery.

PMID- 15956772
TI  - Targeted ablation of prostate carcinoma cells through LH receptor using Hecate
      CGbeta conjugate: functional characteristic and molecular mechanism of cell death
      pathway.
AB  - A Hecate-CGbeta conjugate (lytic peptide and beta-chorionic gonadotropin)
      selectively destroyed cells possessing LH receptors. This study described
      functional characteristics of the conjugate and the molecular mechanism of the
      cell death pathway in prostate cancer cells. Based on in vitro studies, we
      conclude that the conjugate kills cells possessing luteinizing hormone receptors
      (LHR) faster than Hecate alone. Competitive studies have shown that blocking of
      LHR by preincubation with chorionic gonadotropin (100 ng/ml) reduced toxicity of
      the conjugate in low concentrations. Further studies have also shown that the
      conjugate in treated cells both did not induce internucleosomal DNA fragmentation
      and did not induce morphological changes in cells characterized as having
      apoptotic features. These results proved that cells died by necrosis rather than
      apoptosis after the conjugate treatment.

PMID- 15956773
TI  - DNA damages in ovarian surface epithelial cells of ovulatory hens.
AB  - A cause-effect relationship between ovulation and common (surface) epithelial
      ovarian cancer has been suspected for many years. The ovarian surface epithelium
      apparently becomes exposed to genotoxins that are generated during the ovulatory
      process. Intensive egg-laying hens readily develop ovarian carcinomatosis.
      Indeed, elevated levels of potentially mutagenic 8-oxo-guanine adducts were
      detected in avian ovarian epithelial cells isolated from the apical surfaces and
      perimeters of pre-and postovulatory follicles, respectively. Internucleosomal DNA
      fragmentation indicative of apoptosis was evident in ovarian surface epithelial
      cells associated with the formative site of ovulation (stigma line) and
      regressive ruptured follicles. It is conceivable that a genetically altered
      progenitor cell with unrepaired DNA but not committed to death (i.e., a unifocal
      "escape") could give rise to a transformed phenotype. Hence, the high rate of
      ovarian cancer in egg-laying hens could be the consequence of genomic damages to
      the ovarian surface epithelium associated with incessant ovulations, thereby
      increasing the likelihood of mutation and clonal expansion.

PMID- 15956774
TI  - Effect of COX inhibitors and NO on renal hemodynamics following ischemia
      reperfusion injury in normotensive and hypertensive rats.
AB  - The processes involved in the renal damage resulting from ischemia-reperfusion
      injury are poorly understood. This study examined the contribution of
      prostaglandins and nitric oxide (NO) in the vascular responses to ischemia
      reperfusion injury in the kidneys of normotensive and hypertensive rats. Groups
      of Wistar and stroke-prone spontaneously hypertensive rats (SHRSP) were dosed
      with polyethylene glycol vehicle, aspirin (53.5 mg.kg(-1).day(-1)), NO-aspirin
      (100 mg.kg(-1).day(-1)), or celecoxib (10 mg.kg(-1).day(-1)) for 7 days. On day
      7, rats were anesthetized with chloralose/urethane and the left kidney was
      exposed to a 30-min period of ischemia followed by 90-min reperfusion. Renal
      cortical and medullary perfusions were monitored throughout using laser-Doppler
      flowmetry. In the vehicle- and celecoxib-treated Wistar rats, cortical and
      medullary postischemic perfusion was reduced to 66 and 62% and 53 and 62%,
      respectively (all P < 0.05), of baseline. The ischemia-induced reductions in
      cortical and medullary flux were ameliorated in the aspirin and NO-aspirin groups
      where flux fell to 96 and 78% and 105 and 83%, respectively (P < 0.05). There was
      a fall in cortical and medullary flux in the postischemic period in the vehicle
      treated SHRSP to 82 and 77% (P < 0.05). These findings show that nonselective
      cyclooxygenase (COX) inhibition, and to an even greater extent NO donation,
      provided protection to the renal vasculature from ischemic injury in the Wistar
      rat but not in the SHRSP. This would suggest that prostaglandins are less
      important in the development of renal ischemia-reperfusion injury during
      hypertension and both COX isoforms must be inhibited to offset the decrease in
      renal hemodynamics.

PMID- 15956775
TI  - Increased expression of ENaC subunits and increased apical targeting of AQP2 in
      the kidneys of spontaneously hypertensive rats.
AB  - In models of genetic hypertension, renal tubular dysfunction could be involved in
      the increased sodium and water reabsorption. However, the molecular basis for the
      increased renal sodium and water retention remains largely undefined in
      spontaneously hypertensive rats (SHR). We hypothesized that dysregulation of
      renal epithelial sodium channels (ENaC), sodium (co)transporters, or aquaporin-2
      (AQP2) could be involved in the pathogenesis of hypertension in SHR. Six-week-old
      or twelve-week-old SHR and corresponding age-matched Wistar-Kyoto control rats
      (WKY) were studied. In both SHR groups, systolic blood pressure was markedly
      increased, whereas urine output, creatinine clearance, and urinary sodium
      excretion were decreased compared with corresponding WKY. Moreover, urine
      osmolality and urine-to-plasma osmolality ratio were increased compared with WKY.
      Semiquantitative immunoblotting demonstrated that the protein abundance of beta-
      and gamma-subunits of ENaC was increased in the cortex and outer stripe of the
      outer medulla and inner stripe of the outer medulla (ISOM) in SHR, whereas alpha
      ENaC abundance was increased in ISOM. Immunoperoxidase microscopy confirmed the
      increased labeling of beta-ENaC and gamma-ENaC subunits in the late distal
      convoluted tubule, connecting tubule, and cortical and outer medullary collecting
      duct segments. In contrast, subcellular localization of alpha-ENaC, beta-ENaC,
      and gamma-ENaC was not changed. Expression of sodium/hydrogen exchanger type 3,
      bumetanide-sensitive Na-K-2Cl cotransporter, and thiazide-sensitive Na-Cl
      cotransporter was not altered in SHR. AQP2 levels were increased in the ISOM in
      SHR, and immunoperoxidase microscopy demonstrated an increased apical labeling of
      AQP2 in the inner medullary collecting duct in SHR. These results suggest that
      the increased protein abundance of ENaC subunits as well as the increased apical
      targeting of AQP2 may contribute to renal sodium and water retention observed
      during the development of hypertension in SHR.

PMID- 15956776
TI  - Involvement of tyrosine kinase and PI3K in the regulation of OAT3-mediated
      estrone sulfate transport in isolated rabbit renal proximal tubules.
AB  - It was shown previously that OAT3 activity was differentially regulated by
      protein kinases including MAPK, PKA, and PKC. The present study investigated the
      short-term effect of tyrosine kinase and phosphatidylinositol 3-kinase (PI3K) on
      OAT3-mediated organic anion transport in S2 segments of renal proximal tubules.
      Genistein, a tyrosine kinase inhibitor, and wortmannin, a PI3K inhibitor,
      inhibited transport of estrone sulfate, a prototypic substrate for OAT3, in a
      dose-dependent manner. Previously, we showed that epidermal growth factor (EGF)
      stimulated OAT3 activity via the MAPK pathway. In the present study, we
      investigated whether EGF-stimulated OAT3 activity was dependent on tyrosine
      kinase and PI3K. We showed that EGF stimulation of OAT3 was reduced by inhibition
      of tyrosine kinase or PI3K, suggesting that they play a role in the stimulatory
      process. Inhibitory effects also indicated that tyrosine kinase and PI3K are
      involved in the MAPK pathway for EGF stimulation of OAT3 in intact renal proximal
      tubules, with PI3K acting upstream and tyrosine kinase acting downstream of
      mitogen-activated/extracellular signal-regulated kinase kinase activation.

PMID- 15956777
TI  - Association of CD2AP with dynamic actin on vesicles in podocytes.
AB  - The docking protein CD2AP (CD2-associated protein) serves a nonredundant function
      in podocytes as CD2AP knockout mice die of renal failure at the age of 6-7 wk.
      Furthermore, haploinsufficiency due to mutation of the CD2AP gene is associated
      with focal segmental glomerulosclerosis in humans. Although CD2AP has been shown
      to interact with proteins regulating actin polymerization, with proteins of the
      slit diaphragm, and with the endocytic machinery, its critical function in
      podocytes remains unclear. In conditionally immortalized mouse podocytes, we
      demonstrate that CD2AP colocalizes with cortactin and F-actin in spots of < or
      =0.5-microm diameter. Confocal time-lapse microscopy in living podocytes
      expressing GFP-CD2AP or GFP-actin revealed that spots are motile, possess a
      limited lifetime, and are frequently associated with vesicles. A significant
      portion of spot-associated vesicles belongs to a later endosomal-sorting
      compartment, characterized by delayed uptake of fluorescent dextran (10 kDa) and
      by colocalization with Rab4, but not Rab5 and AP-2. Rapid accumulation of
      microinjected G-actin in spots and abrogation of spot motility by jasplakinolide
      demonstrate that spot movements depend on actin polymerization. Furthermore, a
      high turnover (half-time < 10 s) of CD2AP in spots was demonstrated by FRAP
      (fluorescence recovery after photobleaching). Our results demonstrate that CD2AP
      is associated with dynamic actin in a specific late endosomal compartment in
      podocytes, suggesting that CD2AP might be crucially involved in endosomal sorting
      and/or trafficking via regulation of actin assembly on vesicles.

PMID- 15956778
TI  - Activated IGF-1R inhibits hyperglycemia-induced DNA damage and promotes DNA
      repair by homologous recombination.
AB  - The IGF-1R is a genetic determinant of oxidative stress and longevity.
      Hyperglycemia induces an exponential increase in the production of a key danger
      signal, reactive oxygen intermediates, which target genomic DNA. Here, we report
      for the first time that ligand activation of the IGF-1R prevents hyperglycemia
      induced genotoxic stress and enhances DNA repair, maintaining genomic integrity
      and cell viability. We performed single gel electrophoresis (comet assay) to
      evaluate DNA damage in serum-starved SV40 murine mesangial cells (MMC) and normal
      human mesangial cells (NHMC), maintained at high ambient glucose concentration.
      Hyperglycemia inflicted an impressive array of DNA damage in the form of single
      strand breaks (SSBs) and double-strand breaks (DSBs). The inclusion of IGF-1 to
      culture media of MMC and NHMC prevented hyperglycemia-induced DNA damage. To
      determine whether DNA damage was mediated by reactive oxygen species (ROS), ROS
      generation was evaluated, in the presence of IGF-1, or the free radical scavenger
      n-acetyl-cysteine (NAC). IGF-1 and NAC inhibited hyperglycemic-induced ROS
      production and hyperglycemia-induced DNA damage. We next asked whether IGF-1
      promotes the repair of DSB under hyperglycemic conditions, by homologous
      recombination (HRR) or nonhomologous end joining (NHEJ). Repair of DSB by NHEJ
      and HRR was operative in MMC maintained under hyperglycemic conditions. IGF-1
      increased HRR by nearly twofold, whereas IGF-1 did not affect DNA repair by NHEJ.
      IGF-1R enhancement of HRR correlated with the translocation of Rad51 to foci of
      DNA damage. Inhibition of Rad51 expression by short interfering RNA experiments
      markedly decreased percentage of MMC positive for Rad51 nuclear foci and
      increased hyperglycemic DNA damage. We conclude that the activated IGF-1R rescues
      mesangial cells from hyperglycemia-induced danger signals that target genomic DNA
      by suppressing ROS and enhancing DNA repair by HRR.

PMID- 15956779
TI  - Hypoxia-inducible factor modulates tubular cell survival in cisplatin
      nephrotoxicity.
AB  - Hypoxia-inducible factor (HIF)-1 is a transcription factor mediating cellular
      response to hypoxia. Although it is expressed in tubular cells of the ischemic
      kidney, its functional role is not fully clarified in the pathological context.
      In this study, we investigated a role of HIF in tubular cell apoptosis induced by
      cisplatin. HIF-1alpha was expressed in tubular cells in the outer medulla 3 days
      after cisplatin (6 mg/kg) administration. With the in vivo administration of
      cobalt to activate HIF, the number of apoptotic renal tubular cells became much
      smaller in the outer medulla, compared with the vehicle group. We also examined
      the functional role of HIF-1 in vitro using immortalized rat proximal tubular
      cells (IRPTC). In hypoxia, IRPTC that express dominant-negative (dn) HIF-1alpha
      showed impaired survival in cisplatin injury at variable doses (25-100 microM, 24
      h), which was not obvious in normoxia. The observed difference in cell viability
      in hypoxia was associated with the increased number of apoptotic cells in dnHIF
      1alpha clones (Hoechst 33258 staining). Studies on intracellular signaling
      revealed that the degree of cytochrome c release, dissipation of mitochondrial
      membrane potentials, and caspase-9 activity were all more prominent in dnHIF
      1alpha clones than in control IRPTC, pointing to the accelerated signaling of
      mitochondrial pathways. We propose that HIF-1 mediates cytoprotection against
      cisplatin injury in hypoxic renal tubular cells, by reducing the number of
      apoptotic cells through stabilization of mitochondrial membrane integrity and
      suppression of apoptosis signaling. A possibility was suggested that activation
      of HIF-1 could be a new promising therapeutic target for hypoxic renal diseases.

PMID- 15956780
TI  - Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of
      PKA, which contributes to oxidative stress in rat kidney cortex.
AB  - The incidence of diabetic nephropathy has been increasing. Studies have shown
      that oxidative stress (due to increased oxidant production and/or decreased
      antioxidant activity) is a critical underlying mechanism. The principal
      intracellular reductant is NADPH whose production is mainly dependent on glucose
      6-phosphate dehydrogenase (G6PD) activity. Our work in cultured cells previously
      showed that high glucose caused activation of protein kinase A (PKA) and
      subsequent phosphorylation and inhibition of G6PD activity and hence decreased
      NADPH (Zhang Z, Apse K, Pang J, and Stanton RC. J Biol Chem 275:40042-40047,
      2000). The purpose of this study was to determine whether these findings occur in
      diabetic rats (induced by streptozotocin) compared with control. G6PD activity
      and accordingly NADPH levels and glutathione levels were significantly decreased
      in diabetic kidneys compared with control kidneys. Lipid peroxidation was
      significantly increased, which correlated with decreased G6PD activity (r =
      0.48). G6PD expression was significantly reduced, which correlated with decreased
      G6PD activity (r = 0.72). PKA activity and serine phosphorylation of G6PD were
      significantly increased and were closely correlated with decreased G6PD activity
      (r = 0.51 for PKA activity; r = 0.93 for serine phosphorylation of G6PD). Insulin
      treatment and/or correction of hyperglycemia ameliorated the changes caused by
      diabetes. In conclusion, chronic hyperglycemia caused inhibition of G6PD activity
      via decreased expression and increased phosphorylation of G6PD, which therefore
      led to increased oxidative stress.

PMID- 15956781
TI  - Oxidative stress and antioxidant treatment in hypertension and the associated
      renal damage.
AB  - Reactive oxygen species (ROS) are elevated in humans with hypertension many of
      which develop end-stage renal disease (ESRD), and antioxidant capacity is
      decreased. About one-half of essential hypertensives have a salt-sensitive type
      of hypertension, and the amount of renal damage that occurs in salt-sensitive
      hypertensives greatly exceeds that of non-salt-sensitive hypertensives.
      Antioxidant therapy can improve cardiovascular outcomes in humans but only if
      sufficient doses are used. Salt-sensitive hypertensive animal models, especially
      Dahl salt-sensitive rats, have been used to investigate the relationship between
      hypertension, ROS and end-stage renal damage. In experimental salt-sensitive
      hypertension, ROS increase and significant renal damage occur. In the Dahl salt
      sensitive (S) rat on high Na for 3 weeks, renal damage is mild, renal levels of
      superoxide dismutase are decreased, and treatment with Tempol reduces arterial
      pressure. In the Dahl S rat on high Na for 5 weeks, renal damage is severe, GFR
      and renal plasma flow are decreased, and renal superoxide production is high.
      Treatment with vitamins C and E decreases renal superoxide production and renal
      damage and prevents the decrease in renal hemodynamics. Antioxidant treatment
      reduces arterial pressure, aortic superoxide production and renal inflammation in
      DOCA-salt rats, and decreases blood pressure and aortic superoxide release and
      increases bioactive nitric oxide in SHR stroke-prone rats. In conclusion, in both
      human and experimental salt-sensitive hypertension, superoxide production and
      renal damage are increased, antioxidant capacity is decreased, and antioxidant
      therapy can be helpful.

PMID- 15956782
TI  - Mechanisms of suicidal erythrocyte death.
AB  - Erythrocyte injury such as osmotic shock, oxidative stress or energy depletion
      stimulates the formation of prostaglandin E2 through activation of cyclooxygenase
      which in turn activates a Ca2+ permeable cation channel. Increasing cytosolic
      Ca2+ concentrations activate Ca2+ sensitive K+ channels leading to
      hyperpolarization, subsequent loss of KCl and (further) cell shrinkage. Ca2+
      further stimulates a scramblase shifting phosphatidylserine from the inner to the
      outer cell membrane. The scramblase is sensitized for the effects of Ca2+ by
      ceramide which is formed by a sphingomyelinase following several stressors
      including osmotic shock. The sphingomyelinase is activated by platelet activating
      factor PAF which is released by activation of phospholipase A2.
      Phosphatidylserine at the erythrocyte surface is recognised by macrophages which
      engulf and degrade the affected cells. Moreover, phosphatidylserine exposing
      erythrocytes may adhere to the vascular wall and thus interfere with
      microcirculation. Erythrocyte shrinkage and phosphatidylserine exposure
      ('eryptosis') mimic features of apoptosis in nucleated cells which however,
      involves several mechanisms lacking in erythrocytes. In kidney medulla, exposure
      time is usually too short to induce eryptosis despite high osmolarity. Beyond
      that high Cl- concentrations inhibit the cation channel and high urea
      concentrations the sphingomyelinase. Eryptosis is inhibited by erythropoietin
      which thus extends the life span of circulating erythrocytes. Several conditions
      trigger premature eryptosis thus favouring the development of anemia. On the
      other hand, eryptosis may be a mechanism of defective erythrocytes to escape
      hemolysis. Beyond their significance for erythrocyte survival and death the
      mechanisms involved in 'eryptosis' may similarly contribute to apoptosis of
      nucleated cells.

PMID- 15956783
TI  - Rat brown adipose tissue thermogenic features are altered during mid-pregnancy.
AB  - Brown adipose tissue (BAT) thermogenesis is inhibited during late-pregnancy and
      lactation in the rat. However, scarce information concerning BAT functionality
      during mid-pregnancy is available. The aim of this work was to investigate
      uncoupling proteins and leptin expression during placentation in rat BAT as well
      as other key parameters in the thermogenic function of the tissue. BAT
      mitochondrial content was found to be reduced 50% in 11 and 13 day pregnant rats
      as compared to nonpregnant controls, although uncoupling protein 1 (UCP1) content
      was not modified. Furthermore, UCP3 mRNA levels were found to be highly increased
      during this period. beta3-adrenergic receptor (beta3-AR) decreased expression
      resulted in a higher alpha2/beta3 ratio. Finally, leptin mRNA levels in BAT were
      found to be 3-fold up-regulated in pregnant animals. In conclusion, we show the
      existence of profound changes in thermogenic features in BAT during gestational
      days 11 and 13, pointing to the importance of this tissue during mid-pregnancy.

PMID- 15956785
TI  - Metabolism of homovanillamine to homovanillic acid in guinea pig liver slices.
AB  - BACKGROUND/AIMS: Homovanillamine is a biogenic amine that it is catalyzed to
      homovanillyl aldehyde by monoamine oxidase A and B, but the oxidation of its
      aldehyde to the acid derivative is usually ascribed to aldehyde dehydrogenase and
      a potential contribution of aldehyde oxidase and xanthine oxidase is usually
      ignored. METHODS: The present investigation examines the metabolism of
      homovanillamine to its acid derivative by concurrent incubation with monoamine
      oxidase and aldehyde oxidase. In addition, the metabolism of homovanillamine in
      freshly prepared and cryopreserved liver slices is examined and the relative
      contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase
      activity by using specific inhibitors of each oxidizing enzyme is compared.
      RESULTS: Homovanillamine was rapidly converted mainly to homovanillic acid when
      incubated with both momoamine oxidase and aldehyde oxidase. Homovanillic acid was
      also the main metabolite in the incubations of homovanillamine with freshly
      prepared or cryopreserved liver slices, via the intermediate homovanillyl
      aldehyde. The acid formation was 70-75 % inhibited by disulfiram (specific
      inhibitor of aldehyde dehydrogenase), whereas isovanillin (specific inhibitor of
      aldehyde oxidase) inhibited acid formation to a lesser extent (50-55 %) and
      allopurinol (specific inhibitor of xanthine oxidase) had almost no effect.
      CONCLUSIONS: Homovanillamine is rapidly oxidized to its acid, via homovanillyl
      aldehyde, by aldehyde dehydrogenase and aldehyde oxidase with little or no
      contribution from xanthine oxidase.

PMID- 15956784
TI  - C2C12 skeletal muscle cells exposure to phosphatidylcholine triggers IGF-1 like
      responses.
AB  - Glucose uptake by cells in response to stimulation with either IGF-1 or insulin
      is associated with the translocation of GLUT (glucose transporter) proteins from
      intracellular cytoplasmic compartments to the plasma membrane. In response to
      such stimulation, GLUT4 and GLUT1 translocation to the plasma membrane is
      triggered through an increase in their exocytosis involving phospholipase D (PLD)
      activation, disrupting the recycling of intracellular GLUT-containing vesicles
      between the plasma membrane and internal compartments. In skeletal muscle,
      insulin resistance is observed in association with an increase of dipalmitoyl
      phosphatidylcholine, which is also known to interact with PLD. Based on evidence
      that the recycling process is important for GLUT translocation, we decided to
      address whether dipalmitoyl-phosphatidylcholine, a non-translocatable
      phospholipid known to alter the recycling of intracellular vesicles and to
      interact with PLD, can be involved in glucose metabolism. We show that an acute
      change in phospholipid composition, by addition of dipalmitoyl
      phophatidylcholine, leads to GLUT1 translocation to the plasma membrane in
      conjunction to an increase of Akt and GSK3beta phosphorylation, which are
      sensitive to PI3K and PLD inhibitors. Moreover, we also show that long-term
      change in phospholipid composition disrupts both the IGF-1 signalling pathway and
      GLUT1 partitioning within the cells.

PMID- 15956786
TI  - S-adenosylhomocysteine metabolism in different cell lines: effect of hypoxia and
      cell density.
AB  - BACKGROUND/AIMS: The methylation potential (MP) is defined as the ratio of S
      adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy). It was shown
      recently that hypoxia increases AdoMet/AdoHcy ratio in HepG2 cells (Hermes et
      al., Exp Cell Res 294: 325-334, 2004). In the present study, we compared
      AdoMet/AdoHcy ratio and energy metabolism in HepG2, HEK-293, HeLa, MCF-7 and SK
      HEP-1 cell lines under normoxia and hypoxia. METHODS: Metabolite concentrations
      were measured by HPLC. In addition, AdoHcy hydrolase (AdoHcyase) activity was
      determined photometrically. RESULTS: Under normoxia HepG2 cells show the highest
      AdoMet/AdoHcy ratio of 53.4 +/- 3.3 followed by MCF-7 and SK-HEP-1 cells with a
      AdoMet/AdoHcy ratio of 14.4 +/- 1.1 and 21.1 +/- 1.3, respectively. The lowest
      AdoMet/AdoHcy ratios are exhibited by HeLa and HEK-293 cells (6.6 +/- 0.7 and 7.1
      +/- 0.3). Hypoxia does not significantly change the MP in MCF-7 and HeLa cells,
      but alters the MP in HepG2, HEK-293 and SK-HEP-1 cells. These alterations are
      dependent on the cell density. Under normoxia HepG2 cells exhibit AdoHcyase
      activity of 2.5 +/- 0.2 nmol min(-1) mg(-1) protein. All other cell lines show 3
      5 times lower enzyme activity. Interestingly, hypoxia affects AdoHcyase activity
      only in HepG2 cells. CONCLUSIONS: Our data clearly show that the cell lines are
      characterized by different MP and different behavior under hypoxia. That implies
      that a lower MP is not necessarily associated with impaired transmethylation
      activity and cellular function.

PMID- 15956787
TI  - Assessment of relations between clinical outcome of ischemic stroke and activity
      of inflammatory processes in the acute phase based on examination of selected
      parameters.
AB  - BACKGROUND AND PURPOSES: Inflammatory factors play an important role in the
      pathogenesis of ischemic stroke. They may influence circulation during the acute
      phase of stroke and enhance the ischemic region. MATERIALS AND METHODS: We
      examined 51 patients--36 patients in the early stage of stroke, i.e. the first 24
      h after onset. Of these, 15 patients had infection and 21 had no infection during
      the week preceding stroke. There were 15 patients with noninflammatory diseases
      in the control group. We analyzed parameters of inflammation such as: activity of
      serum chitotriosidase by fluorimetric assay, C-reactive proteins (CRP), number of
      white body cells (WBCs), IgG and fibrinogen. We also assessed the neurological
      stage according to the Scandinavian Stroke Scale (SSS). RESULTS: In our study, we
      observed a statistically significant difference (p < 0.05) in the activity of
      most parameters of inflammation. This difference could be seen in the levels of
      CRP, number of WBCs and the activity of chitotriosidase, apart from IgG and
      fibrinogen, between the control group and groups with versus without infection. A
      significantly increased level of CRP (p < 0.0005) and fibrinogen (p > 0.01) was
      found on the first day in the stroke group as compared to the control group. The
      neurological stage on day 4 after stroke, assessed according to the SSS, was
      significantly worse in the group of patients with infection before stroke than in
      stroke patients without infection (p < 0.008). CONCLUSION: These results suggest
      the importance of active inflammatory processes in the pathogenesis of stroke. We
      observed increased activity of chitotioridase, a parameter of the inflammatory
      process, in stroke. This study is one more proof that inflammatory processes
      caused by infection may influence the occurrence of stroke and worsen its
      outcome. It could be another step towards understanding immunological processes
      during the acute phase of stroke. The study may also help establish new
      diagnostic and therapeutic strategies and could be a useful tool for prophylaxis.

PMID- 15956788
TI  - Hyperinsulinemia and insulin insensitivity in women with nonclassical congenital
      adrenal hyperplasia due to 21-hydroxylase deficiency: the relationship between
      serum leptin levels and chronic hyperinsulinemia.
AB  - BACKGROUND/AIM: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency (NC-CAH) is associated with hyperandrogenemia, chronic anovulation,
      hirsutism, acne and adrenal hyperplasia. A few studies have shown
      hyperinsulinemia and insulin insensitivity in NC-CAH. Hyperinsulinemia can
      stimulate leptin secretion, and androgens can inhibit leptin secretion. Thus, we
      designed a study to investigate the insulin levels and insulin sensitivity and
      the effect of chronic endogenous hyperinsulinemia and androgens on leptin in
      patients with NC-CAH. METHODS: Eighteen women with untreated NC-CAH and 26
      normally cycling control women with a similar body mass index (BMI) were studied.
      Basal hormones, fasted and fed insulin levels, leptin and stimulated 17
      hydroxyprogesterone (17-OHP) concentrations were studied. Homeostasis model
      assessment was used to assess insulin sensitivity. RESULTS: The basal 17-OHP, the
      free testosterone (fT) and dehydroepiandrosterone sulfate (DHEA-S) were
      significantly different in the 2 groups (p < 0.05). Fasting and fed insulin
      levels of the NC-CAH group were higher than those of the control group (p < 0.05)
      and insulin sensitivity was lower in NC-CAH than in controls (p < 0.05). Insulin
      levels were correlated with fT and 17-OHP (p < 0.05). Serum leptin levels for NC
      CAH (25.9 +/- 12.5 microg/l) did not differ from the controls (25.4 +/- 12.06
      microg/l) and were positively correlated with BMI (r = 0.725) and percent body
      fat (r = 0.710) for both groups (both p < 0.001). Leptin levels were not
      correlated with estrogen or androgens, gonadotropins or insulin levels.
      CONCLUSION: Hyperinsulinemia and insulin insensitivity associated with
      hyperandrogenism were detected in untreated NC-CAH patients as in previous
      reports, whereas serum leptin levels did not differ from those of controls.

PMID- 15956789
TI  - Comparative study of tolerance between unmodified and high doses of chemically
      modified allergen vaccines of Dermatophagoides pteronyssinus.
AB  - BACKGROUND: The physiochemical modification of allergens to reduce allergenicity,
      while retaining immunogenicity, provides a chance for the administration of
      higher doses of immunotherapy, with a decreased risk of systemic reactions.
      OBJECTIVE: To evaluate the safety of doses of depigmented glutaraldehyde
      polymerized vaccine of Dermatophagoides pteronyssinus increasing those used in
      normal clinical conditions in comparison with regular doses of a non-modified
      vaccine. MATERIALS AND METHODS: The study was double-blind, parallel and included
      two patient groups. Twenty-three patients were treated weekly during 9 visits for
      the build-up phase, followed by 2-weekly maintenance doses (a total of 11
      injections per patient). Eleven patients (mean age 22 years) received
      immunotherapy with the standardized modified vaccine. The maximum dose used was
      the result of depigmenting and polymerizing 100 times the maximum dose used with
      the native extract. The maximum concentration used was 990 mug/ml of freeze-dried
      material. Twelve patients (mean age 24 years) received a standardized, unmodified
      allergenic extract. The maximum concentration used was 70 mug of freeze-dried
      material/ml, with a potency of 10 HEP(L)/ml. The tolerance was evaluated
      recording all the side reactions related to immunotherapy and graded following
      the recommendations of the European Academy of Allergology and Clinical
      Immunology. RESULTS: In both groups, all immediate local reactions were
      clinically not relevant. Patients treated with the native extract experienced 42
      local immediate and 24 delayed reactions (1 of them had a diameter >10 cm),
      whereas patients treated with the modified extract experienced 30 local immediate
      and 21 delayed reactions (2 of them had a diameter >10 cm). Four systemic
      reactions in 2 patients, 1 immediate of grade 1 and 3 delayed of grade 2 were
      reported in the group treated with native extract and 1 delayed of grade 2 in the
      group treated with the modified preparation. CONCLUSIONS: The modified extract of
      D. pteronyssinus, used at concentrations which are 10 times higher than those
      regularly administered in clinical practice, demonstrated to be safe to treat D.
      pteronyssinus-sensitive patients. The majority of the local reactions (immediate
      and delayed) were clinically not relevant (diameter <5 cm). No systemic reactions
      of grade 3 or 4 were noted.

PMID- 15956790
TI  - Mice vaccinated with allergen-pulsed myeloid dendritic cells are not protected
      from developing allergen-induced Th2 responses.
AB  - BACKGROUND: Dendritic cells (DC) play a decisive role in the induction of
      allergen-induced Th1 and Th2 responses. Since the induction of allergen-specific
      Th1 responses has shown to inhibit allergen-induced Th2-type inflammation, in
      this study we investigated whether manipulated myeloid-derived DC pulsed with the
      specific allergen would predominantly induce allergen-specific Th1 responses
      thereby reducing the development of Th2 responses. METHODS: Murine bone marrow
      (BM)-DC were generated and pulsed with ovalbumin (OVA) and CpG
      oligodeoxynucleotides (CpG-ODN). Langerhans cells (LC) were also isolated and
      pulsed in vitro with OVA. Subsequently, mice were vaccinated intravenously with
      either CpG/OVA-pulsed BM-DC or OVA-pulsed LC, and the protocol to induce OVA
      specific Th2 responses using OVA/alum sensitization was initiated. Airway
      inflammation and OVA-specific serum antibody levels were evaluated 6 days after
      the intranasal challenge with OVA. RESULTS: The application ofCpG/OVA-pulsed BM
      DC was unable to reduce airway eosinophilia and inflammation in OVA/alum
      immunized mice. OVA-specific IgG1 or IgE serum levels were also not reduced. The
      experiments using LC pulsed with OVA yielded similar results. However, mice
      vaccinated with CpG/OVA-pulsed BM-DC had greatly enhanced levels of serum OVA
      specific IgG2a, suggesting the induction of allergen-specific Th1 responses in
      vivo. Moreover, allergen-induced mast cell degranulation was decreased using this
      approach. CONCLUSIONS: Taken together, our results demonstrated that the
      vaccination with OVA-pulsed BM-DC matured with CpG-ODN or OVA-pulsed LC did not
      result in a reduction in allergen-specific Th2 responses in a murine model of
      severe atopic asthma. Other DC-based vaccination strategies should be evaluated
      in order to prevent the development of allergic disorders.

PMID- 15956791
TI  - Accumulation of CXCR3-expressing eosinophils and increased concentration of its
      ligands (IP10 and Mig) in bronchoalveolar lavage fluid of patients with chronic
      eosinophilic pneumonia.
AB  - BACKGROUND: Since human peripheral eosinophils have been shown to migrate to the
      CXC chemokine receptor 3 (CXCR3) ligands IFN-gamma-inducible protein 10 (IP10)
      and monokine induced by IFN-gamma (Mig), this confirms that CXCR3 is functionally
      expressed on these cells. IP10 expression has been shown to be increased in the
      airways of asthmatics. Eosinophil accumulations are found in bronchoalveolar
      lavage fluid (BALF) from patients with chronic eosinophilic pneumonia (CEP). To
      examine the contribution of IP10 and Mig in the pathogenesis of CEP, we measured
      the concentration of IP10 and Mig, and evaluated the expression of CXCR3 on
      eosinophils in BALF taken from patients with CEP. METHODS: The concentrations of
      IP10 and Mig in BALF were measured by ELISA. The proportion of CXCR3-expressing
      CD4+ T cells and CD16-negative eosinophils was determined by flow cytometry.
      RESULTS: The BALF concentrations of IP10 and Mig were higher in patients with
      CEP, as well as in patients with sarcoidosis, when compared to healthy controls.
      The absolute number of CXCR3+ CD4+ T cells was significantly higher in the BALF
      of patients with sarcoidosis, but not in the patients with CEP, when compared to
      healthy volunteers. There were higher percentages of CXCR3-expressing eosinophils
      in the BALF than in the peripheral blood of patients with CEP. CONCLUSIONS: Our
      findings suggest that IP10 and Mig contribute to the accumulation of CXCR3
      expressing eosinophils in the lungs of patients with CEP, and modulate the
      eosinophilic inflammation of the lung.

PMID- 15956792
TI  - Why do lipid transfer protein-hypersensitive patients tolerate bean (and other
      legumes)?
AB  - BACKGROUND: Patients allergic to nonspecific lipid transfer protein (LTP)
      frequently score positive on SPT with legumes but virtually never report adverse
      reactions eating these foods. OBJECTIVE: This study investigated the IgE
      reactivity to legumes of LTP-allergic patients and aimed to establish whether
      legumes can be considered safe in LTP-allergic patients. METHODS: Skin reactivity
      as well as clinical allergy to bean and pea were evaluated in a large cohort of
      LTP-hypersensitive patients. Sera from 12 patients showing clinical allergy to a
      number of botanically unrelated plant-derived foods and high levels of IgE to
      peach LTP were employed in in vitro studies (ELISA, ELISA inhibition, SDS
      PAGE/immunoblot) aiming to investigate IgE reactivity to bean. RESULTS:
      Preabsorption of patients' sera with boiled bean extract did not cause any loss
      of IgE reactivity to peach LTP (whereas boiled apple totally abolished it).
      Immunoblot analysis did not show any IgE reactivity to bean proteins at about 10
      kDa, and the SDS profile of bean showed little or no staining at 10 kDa.
      CONCLUSION: Sera from LTP-allergic patients do not seem to show any IgE
      reactivity to 10-kDa proteins in bean. Whether this is caused by epitopic
      differences between Rosaceae and bean LTPs or by the fact that LTP is not
      expressed in bean remains to be established. This study explains why virtually
      all LTP-allergic patients tolerate legumes and suggests that these foods should
      be considered safe for patients sensitized to this protein.

PMID- 15956793
TI  - Significance of anti-hbc in the absence of other hepatitis B markers in a college
      aged population.
AB  - A study of 291 college students in the Houston (Tex., USA) area was performed to
      determine the relationship between alanine aminotransferase (ALT) level and
      antibodies to the hepatitis B virus (HBV) core antigen (anti-HBc) in the absence
      of other HBV markers (referred to as isolated anti-HBc). Participants were drawn
      from three groups: those positive only for anti-HBc (cases), those positive for
      hepatitis B surface antigen, a marker of acute/chronic HBV infection (control
      group 1), and those with no previous exposure to the HBV (control group 2). There
      were no significant differences between the groups in percentages of subjects
      with an elevated ALT level. The mean ALT level from active HBV infections was
      highest with HBV-negative controls having the lowest mean ALT concentration (p =
      0.06), but no significant differences were found between ALT levels of those with
      isolated anti-HBc and either control group. This study may further aid in
      determining the presence of any liver damage when testing positive only for the
      antibodies to HBc.

PMID- 15956794
TI  - Differential astrocyte response to Theiler's murine encephalomyelitis virus
      infection.
AB  - OBJECTIVES: We aimed to address if selective astrocyte apoptosis is involved in
      the lack of murine demyelinating disease following infection by the L*-1 variant
      of Theiler's virus. In addition, we investigated whether L*-1-infected astrocytes
      were able to selectively express molecules whose effects would play a role as
      pathogenic factors. METHODS: Murine cultured astrocytes were infected with two
      Theiler viruses, the DA strain and the mutated DA variant L*-1, which does not
      synthesize the out of frame L* protein. RESULTS: Neither DA nor L*-1 provoked
      apoptosis, although they replicated in astrocytes inducing GFAP and iNOS
      expression, as well as subsequent nitric oxide production. In addition, both
      viruses caused an enhanced expression of ICAM-1, VCAM-1 and decay accelerating
      factor (DAF). In this connection, values of VCAM-1 and DAF induced by L*-1 were
      higher and lower, respectively, than those induced by DA. CONCLUSIONS: Since no
      apoptosis was found, such mechanism would not be involved in the lack of TMEV
      induced demyelinating disease by L*-1. In contrast, selective expression of VCAM
      1 and DAF molecules induced by L*-1 could have a role in virus clearance from the
      central nervous system.

PMID- 15956795
TI  - Improved attachment of natural HCV isolate to Daudi cells upon elimination of
      immune complexes and close pH control.
AB  - OBJECTIVES: To study the viral requirements for attachment, entry and infection
      using natural isolates of HCV (infectious plasma of a patient infected with HCV
      from genotype 1b) and a cell line which has previously been shown to support HCV
      replication (Daudi cells). METHODS: We studied attachment of HCV to Daudi cells,
      a human B-cell line. Quantification was done by real-time RT-PCR. RESULTS: The
      best attachment levels were obtained using plasma depleted of immunocomplexes.
      Results of kinetics of HCV attachment to Daudi cells show that attachment is
      maximum at pH 7.0, and that it decreased drastically at any other pH studied
      (5.5, 6.0, 6.5, 7.5 and 8.0). CONCLUSIONS: Depletion of immunocomplexes and pH
      control during infection are important parameters to improve attachment of HCV to
      Daudi cells using plasma as a natural source of virus.

PMID- 15956796
TI  - Selective cytolysis of tumor cells by mumps virus S79.
AB  - We studied the sensitivity of several human cancer cell strains (HeLa, HT1080,
      SPC-A1, and ACHN) and normal cell strains (MRC-5 and Wish) to mumps virus (MuV)
      S79, a live attenuated vaccine strain. These cells exhibited a differential
      sensitivity to infection with MuV, and the susceptible sequences were ACHN > HeLa
      > HT1080 > SPC-A1 > Wish > MRC-5. In experiments in vivo, nude mice with HT1080
      fibrosarcoma xenografts were randomly divided into three groups for intratumoral
      treatment with MuVS79, UV-inactivated MuVS79, and PBS. At 10(7) PFU, live MuVS79
      injection caused in 7 of 9 mice complete regression by day 15 while rapid tumor
      growth occurred in all 9 mice treated with PBS. Rapid tumor progression also
      occurred in all 8 mice treated with UV-inactivated virus; however, tumor growth
      was delayed in the logarithmic phase relative to the PBS-treated tumors.

PMID- 15956797
TI  - Development and evaluation of a sensitive PCR-ELISA for detection of adenoviruses
      in feces.
AB  - OBJECTIVE: Most of the PCR-based assays for the detection of adenoviruses require
      gel electrophoresis for resolution, which is time- and work-consuming and
      interpretation difficulties often occur. Therefore our objective was to develop
      and evaluate a PCR-ELISA for broad detection of adenoviruses, that is easy to
      perform and leads to an increase of specificity in virus detection. METHODS: A
      total of 64 fecal specimens from patients with acute gastroenteritis, previously
      tested negative for other viruses than adenovirus and for bacterial pathogens,
      were tested for adenovirus in parallel with an Antigen-ELISA, virus isolation in
      cell culture, with a previously published hybridization-based PCR and our newly
      developed semi-nested PCR-ELISA. RESULTS: The new PCR-ELISA turned out to be the
      best method with 26 samples positive for adenovirus. Of these, 22 became positive
      by Ag-ELISA, 19 by virus isolation in cell culture and only 14 by the previously
      published hybridization-based PCR. CONCLUSION: The semi-nested PCR-ELISA is a
      sensitive, reliable and rapid method for the detection of enteric adenoviruses
      from fecal samples.

PMID- 15956798
TI  - Activation of interferon-stimulated response element in huh-7 cells replicating
      hepatitis C virus subgenomic RNA.
AB  - Interferon-alpha (IFN(alpha)) binds to receptors on the cell surface, which
      initiate a cascade of signal transduction pathways that leads to transcription of
      selected genes. This transduction pathway involves binding of transcription
      factors to a common cis-acting DNA sequence called IFN-stimulated response
      element (ISRE). To test whether these signaling pathways are functional in
      hepatitis C virus (HCV)-replicating cells, we studied the regulation of ISRE
      mediated transcription of firefly luciferase gene in stable replicon cell lines.
      A plasmid construct was prepared (pISRELuc) which contains four tandem repeats of
      9-27 ISRE sequences positioned directly upstream of the herpes virus 1 thymidine
      kinase promoter TATA box that drives the expression of firefly luciferase.
      Regulation of ISRE-mediated expression of firefly luciferase by IFN(alpha) was
      studied by transfecting this clone into Huh-7 cells replicating HCV subgenomic
      HCV RNA. The significance of ISRE-mediated transcriptional activation was studied
      in a replicon cell line by pretreatment of cells with actinomycin D, which
      inhibits cellular DNA-dependent RNA transcription. IFN treatment activates ISRE
      mediated expression of luciferase, indicating that this pathway is functional in
      Huh-7 cells. Activation of ISRE-mediated transcription of luciferase is
      relatively high in two Huh-7 stable cell lines replicating HCV subgenomic RNA.
      Inhibition of ISRE-mediated transcription of luciferase by actinomycin D also
      makes HCV replication totally resistant to IFN(alpha). These in vitro studies
      suggest that activation of IFN-inducible genes is important in mounting a
      successful antiviral response against HCV.

PMID- 15956799
TI  - Varicella-zoster virus infection influences expression and organization of actin
      and alpha-tubulin but does not affect lamin A and vimentin.
AB  - OBJECTIVE: The aim of this study was to examine the effects of varicella-zoster
      virus (VZV) infection on the cytoskeletal components actin, lamin A, alpha
      tubulin and vimentin. METHODS: The expression patterns of these four proteins
      during VZV infection were studied by Northern and Western blotting. The filaments
      were also studied in their cellular environment by immunofluorescence using
      confocal microscopy. Treatment with nocodazole and cytochalasin B was performed
      to examine the effects of the destruction of actin or tubulin networks on the VZV
      replicative cycle. RESULTS: The amounts of the mRNAs of actin, lamin A, alpha
      tubulin and vimentin decreased slightly at 48 h post infection (p.i.) with VZV.
      The cellular content of the lamin A protein appeared to remain stable during the
      time period analyzed, whereas the amounts of actin, alpha-tubulin and vimentin
      decreased slightly at 24 h p.i. until the end of the viral cycle. Rearrangement
      of microfilaments and microtubules was observed at 24 h p.i. The addition of
      nocodazole or cytochalasin B decreased viral replication. CONCLUSIONS: During the
      VZV replicative cycle, tubulin and actin networks undergo significant changes
      including fiber elongation. If destroyed intentionally, viral replication is
      diminished, suggesting that these systems are vital for an efficient infection
      and viral replication.

PMID- 15956800
TI  - Expression and characterization of rubella virus glycoprotein E1 in yeast cells.
AB  - OBJECTIVES: To express E1 glycoprotein of rubella virus (RuV) strain JR23 in
      yeast and develop a diagnostic assay using expressed E1 protein as coating
      antigen in comparison with other diagnostic assays. METHODS: cDNA of E1 open
      reading frame of RuV was PCR amplified using plasmid pMD18-T-E1 as template and
      cloned into plasmid pBluscriptII SK+. After being confirmed by PCR, restriction
      endonuclease digestion and sequencing, pBluscriptII SK(+)-E1 plasmid DNA was
      digested by restriction endonuclease EcoR I and Xba I, and a fragment of 1.5 kb
      was isolated and cloned into a yeast expression pGAPZ(alpha)A, resulting in
      pGAPZ(alpha)A-E1. After confirmation by sequencing, pGAPZ(alpha)A- E1 was
      transformed into yeast GS115 cells with LiCl method. E1 protein expression in
      GS115 was analyzed by SDS-PAGE and Western blot. An indirect ELISA was developed
      using the recombinant E1 protein as coating antigen for detecting RuV E1
      antibodies in 90 serum samples. To compare the specificity, sensitivity and
      reproducibility of the assay with other methods, the same serum samples were also
      assayed by RuV culture medium as coating antigen (Jingmei kit and German RECI
      kit). Statistical analyses were performed to compare the differences among these
      methods and to determine which coating antigen source, the recombinant E1 protein
      or RuV-infected culture medium, is more suitable for the assay. RESULTS: A
      fragment of 1.5 kb, corresponding to the full open reading frame of E1, was PCR
      amplified and cloned in yeast expression vector. The clone was confirmed by
      restriction digestion, PCR and sequencing. E1 as a secretive protein was
      successfully expressed by GS115. Its molecular weight was about 58 kDa. SDS-PAGE
      showed that the recombinant protein was expressed efficiently and constantly in
      Pichia pastoris GS115 cells. The expression level reached a peak 48 h after
      culturing and stabilized thereafter. E1 protein was detected in both supernatant
      and cells. Western blot showed that the secretive E1 protein in the supernatants
      could react with both the anti-RuV-positive serum and a monoclonal antibody
      against E1. However, E1 protein derived from cells could only react with the anti
      RuV-positive serum, polyclonal antibody, but not the monoclonal antibody.
      Compared with the German RECI kit, the sensitivity, specificity, and accordance
      rate of the assay using recombinant E1 protein as coating antigen were 67.11,
      71.43 and 67.78%, respectively, while those of the assay using RuV-infected
      culture medium as coating antigen were 50, 78.57 and 54.44%, respectively.
      Compared with the German RECI kit, the sensitivity, specificity, and accordance
      rate of the ELISA assay using the Jingmei kit were 84.71, 71.43 and 82.22%,
      respectively. The data indicated that recombinant E1 protein derived from the
      yeast expression system can serve as a better source than RuV-infected cell
      medium as coating antigen for detecting antibodies against RuV in the indirect
      ELISA assay. Statistical analysis of the data generated from two independent
      experiments using recombinant E1 protein as coating antigen indicated that the
      assay was very consistent with no statistically significant difference between
      the two experiments (p > 0.05). 76 out of 90 serum samples were detected positive
      using the German RECI kit, while 68, 55 and 41 samples were positive using the
      Jingmei kit, recombinant E1 and RuV-infected cell medium, respectively.
      Statistical analyses indicated that the positive rates were significantly
      different among all four assays (p < 0.05) except for one pair (German RECI kit
      and the Jingmei kit: p > 0.05). Comparing the positive rates obtained from the
      assay using recombinant E1 and that using RuV-infected cell medium, it seems that
      the recombinant E1 protein is a better source than RuV culture medium as coating
      antigen in the indirect ELISA assay for detection of RuV antibody. CONCLUSIONS:
      The recombinant yeast expression vector of RuV E1 glycoprotein was constructed
      successfully. The E1 protein as a secretive protein was successfully expressed by
      GS115 and maintained its antigenicity very well. As coating antigen, the
      recombinant E1 protein served a better source than RuV culture medium in the
      indirect ELISA method for the detection of RuV antibody.

PMID- 15956802
TI  - Inhibition of influenza-virus-induced apoptosis in chorion cells of human fetal
      membranes by nordihydroguaiaretic Acid.
AB  - OBJECTIVES: It has been postulated that the pathogenesis of influenza virus
      infection involves not only the virus-proliferation-mediated apoptotic cell death
      in infected cells, but also a direct reactive oxygen species (ROS)-induced
      cellular injury in the infected organs. We examined effects of an antioxidant,
      nordihydroguaiaretic acid (NDGA), on apoptosis induction and viral proliferation.
      Subsequently, the results were compared with those of pyrrolidine dithiocarbamate
      (PDTC), another antioxidant. METHODS: The levels of ROS production were measured
      with 2',7'-dichlorofluorescein diacetate; apoptosis induction and viral
      proliferation were analyzed by DNA fragmentation and plaque-forming assays,
      respectively. RESULTS: The treatment of infected cells with NDGA inhibited ROS
      overproduction, apoptotic DNA fragmentation and virus proliferation. The maximum
      inhibition against DNA fragmentation (76%) was observed with 500 microM NDGA. The
      antiviral activity of NDGA against influenza virus was more potent than that of
      PDTC. CONCLUSIONS: The present study, therefore, suggests for the first time that
      NDGA, a known antioxidant reagent, inhibits the induction of apoptosis in human
      fetal membrane chorion cells infected with influenza virus through the more
      potent antiviral activity than that of PDTC.

PMID- 15956801
TI  - Efficient therapeutic gene expression in cultured rat hippocampal neurons
      mediated by human foamy virus vectors: a potential for the treatment of
      neurological diseases.
AB  - Vectors derived from human foamy virus (HFV), with their nonpathogenic nature and
      a wide tissue tropism, have been successfully used as retroviral gene transfer
      vehicles. However, transduction of primary hippocampal neurons (HNs) with HFV
      vectors has little been studied. To investigate the potential of HFV-derived
      vector in gene therapy for neurological diseases, efficient foreign gene
      expression in cultured rat HNs was first demonstrated by successful enhanced
      green fluorescent protein (EGFP) transduction through a HFV vector bearing an
      EGFP expression cassette. Furthermore, we tested the effect on HNs that were
      transduced by a novel HFV vector expressing the human glutamic acid decarboxylase
      (GAD) cDNA, a therapeutic gene for neurological disorders such as epilepsy and
      Parkinson's disease. The transduced HNs showed significant increase in isoform
      specific expression of GAD, synthesis of gamma-aminobutyric acid (GABA) and
      stimulation-evoked GABA release. These findings indicated for the first time that
      cultured rat HNs could be efficiently transduced by HFV vectors, and the GAD
      expressing HFV vector has potential therapeutic value in the treatment of
      neurological diseases.

PMID- 15956804
TI  - Non-occlusive mesenteric ischemia in chronically dialyzed patients: a disease
      with multiple risk factors.
AB  - BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) can be a fatal complication
      in dialysis patients. Intradialytic hypotension is usually the precipitating
      factor. The occurrence of 16 cases in 5 years (1998-2002), compared with only 4
      in previous years, led us to investigate other risk factors contributing to NOMI.
      A control group of stable hemodialysis patients was used for comparison. RESULTS:
      20 patients were studied: 17 diagnosed surgically, and 3 clinically. The mean age
      was 70.8 +/- 1.8 years, and the male:female ratio 7:13. Nineteen patients were on
      hemodialysis. Clinically overt atherosclerosis was present in 17 patients.
      Preceding dialysis-associated hypotension was identified in all patients studied
      and access thrombosis in 6 patients. In all patients, abdominal pain was the
      presenting symptom. Initial abdominal examination was unimpressive in 16
      patients. The hemoconcentration, leukocytosis and metabolic acidosis were the
      most prominent laboratory findings. 5/11 abdominal sonograms showed intestinal
      pathology. 2/3 angiographies were diagnostic. Three patients responded to early
      fluid challenge and did not require surgery. Pathology was related to the area of
      the superior mesenteric artery in all 15 patients operated. Twelve (60%) patients
      died from the event. The 1-year mortality rate was 17/20 patients (85%). Possible
      contributing factors, other than dialysis-associated hypotension, included: high
      dose recombinant human erythropoietin (rhEPO) therapy (179 +/- 35 vs. 116 +/- 10
      U/kg/week in the control group, p < 0.05); metastatic calcifications (abdominal
      aorta 14/14, aortic valve 11/18; medial calcification of mesenteric arteries in
      2/11 pathology specimens); digoxin, and hypoalbuminemia. CONCLUSIONS: The
      increased incidence of NOMI in dialysis patients may be related to overly
      aggressive rhEPO therapy and the unsuspected presence of mesenteric arterial
      medial calcifications. Identification of patients at risk, prevention of
      intradialytic hypotension and a controlled increase in dry weight may help to
      reduce the incidence of NOMI in chronically dialyzed patients.

PMID- 15956803
TI  - Abnormal cytokine synthesis as a consequence of increased intracellular oxidative
      stress in children treated with dialysis.
AB  - BACKGROUND/AIM: End-stage renal disease (ESRD) induces a clinical state of
      immunodeficiency with a higher incidence of infections and higher mortality due
      to infectious complications compared with the normal population. The definite
      mechanism responsible for the host defense alterations is not well understood.
      The aim of the study was to investigate intracellularly the relationship between
      cytokine synthesis and oxidative stress in peripheral blood lymphocytes in
      children with ESRD. METHODS: Twenty-one children (age 11.7 +/- 5.8 years) with
      ESRD treated with hemodialysis (HD; n = 10) and peritoneal dialysis (PD; n = 11)
      were studied. Nine healthy children of comparable age formed the control group.
      To determine intracellular oxidative stress we used dihydrorhodamine-123 (DHR),
      which after oxidation to rhodamine-123 (RHO) emitted a bright fluorescent signal.
      Intracellular oxidation of DHR in T lymphocytes reflected intracellular oxidative
      stress. The intracellular synthesis of cytokines (IL-2, IFN-gamma, IL-4, IL-6)
      was also measured. Both parameters were detected at a single-cell level by flow
      cytometry. Lymphocyte subsets were evaluated using the monoclonal antibodies
      conjugated with fluorochromes. RESULTS: We found that in T lymphocytes the mean
      fluorescence intensity (MFI), which reflected intracellular oxidative stress, was
      increased in ESRD patients compared to the controls (CD3+: 34.77 +/- 11.55 vs.
      22.55 +/- 4.97, p < 0.01; CD3+CD8+: 34.31 +/- 12.17 vs. 20.77 +/- 4.89, p < 0.01;
      CD3+CD4+: 36.06 +/- 6.98 vs. 24.44 +/- 7.68, p < 0.001). HD patients showed
      slightly higher MFI compared to PD patients in CD3+ cells (39.32 +/- 11.70 vs.
      30.63 +/- 10.20, NS), in CD3+CD8+ cells (37.90 +/- 14.32 vs. 31.06 +/- 9.34, NS)
      and in CD3+CD4+ cells (40.10 +/- 2.28 vs. 29.33 +/- 7.06, p < 0.001). The
      intracellular synthesis of IL-2 was higher in ESRD patients compared to the
      controls, both in CD3+ cells (31.34 +/- 9.80 vs. 20.49 +/- 15.26%, p < 0.05) and
      in CD3+CD4+ cells (36.10 +/- 8.69 vs. 24.03 +/- 16.95%, p < 0.05). The
      intracellular synthesis of IFN-gamma, IL-4 and IL-6 was significantly lower in
      the ESRD group compared to the controls. Interestingly, in patients treated with
      HD, negative correlations between the degree of intracellular oxidative stress
      and intracellular cytokine synthesis in CD3+ lymphocytes were found. CONCLUSION:
      Our results show that patients with ESRD, especially those treated with HD,
      present increased oxidative stress in T lymphocytes, which may lead to decreased
      cytokine synthesis and abnormal immune response.

PMID- 15956805
TI  - Intravenous calcitriol therapy increases serum concentrations of fibroblast
      growth factor-23 in dialysis patients with secondary hyperparathyroidism.
AB  - BACKGROUND/AIMS: Fibroblast growth factor-23 (FGF-23) is a recently discovered
      phosphaturic factor. Although increased levels of serum FGF-23 have been reported
      in dialysis patients, the role of high FGF-23 levels remains unclear. Since FGF
      23 is associated also with vitamin D metabolism, we examined the changes of serum
      FGF-23 levels in chronic dialysis patients treated with intravenous calcitriol
      therapy. METHODS: Thirty patients with severe secondary hyperparathyroidism were
      treated with intravenous calcitriol (0.5-1.0 microg) two or three times per week
      for 6 months. The changes of serum levels of calcium, phosphate, intact PTH, and
      FGF-23 were evaluated. RESULTS: Baseline serum FGF-23 levels were markedly high.
      By intravenous calcitriol therapy, intact PTH levels decreased effectively in the
      first month (p < 0.001). In contrast, FGF-23 levels increased gradually during
      the study period (p = 0.027). The Delta serum FGF-23 level was significantly
      correlated with the total doses of calcitriol injected intravenously in 6 months
      in patients with refractory secondary hyperparathyroidism (R2 = 0.147; p =
      0.036). CONCLUSIONS: Intravenous calcitriol decreased serum intact PTH level and
      increased serum FGF-23 levels significantly. Extremely high levels of serum FGF
      23 in these patients may be attributed, at least in part, to the cumulative dose
      of vitamin D.

PMID- 15956806
TI  - Clinical research in primary stroke prevention: needs, opportunities, and
      challenges.
AB  - Most ( approximately 70%) of strokes are first-ever strokes, and hence to
      substantially reduce the neurological burden, primary prevention is crucial.
      Here, highlights of the National Institute of Neurological Disorders and Stroke
      workshop "Stroke Risk Assessment and Future Stroke Primary Prevention Trials"
      held January 12-13, 2004 are summarized. The Workshop discussions focused on
      stroke risk assessment; the high-risk vs. population-based approaches to primary
      prevention; desirable characteristics of candidate treatments and potential novel
      treatments, such as the 'polypill'; subclinical disease as risk assessment tool
      and as surrogate outcome, and methodological issues in stroke primary prevention
      trials. The importance of assessing cognitive decline as an important consequence
      of covert and overt vascular injury of the brain was emphasized. The scientific
      or logistic barriers to stroke primary prevention trials are challenging, but are
      not insurmountable.

PMID- 15956807
TI  - Is the effect of alcohol on risk of stroke confined to highly stressed persons?
AB  - BACKGROUND: Psychological stress and alcohol are both suggested as risk factors
      for stroke. Further, there appears to be a close relation between stress and
      alcohol consumption. Several experimental studies have found alcohol consumption
      to reduce the immediate effects of stress in a laboratory setting. We aimed to
      examine whether the association between alcohol and stroke depends on level of
      self-reported stress in a large prospective cohort. METHODS: The 5,373 men and
      6,723 women participating in the second examination of the Copenhagen City Heart
      Study in 1981-1983 were asked at baseline about their self-reported level of
      stress and their weekly alcohol consumption. The participants were followed-up
      until 31st of December 1997 during which 880 first ever stroke events occurred.
      Data were analysed by means of Cox regression modelling. RESULTS: At a high
      stress level, weekly total consumption of 1-14 units of alcohol compared with no
      consumption seemed associated with a lower risk of stroke (adjusted RR: 0.57, 95%
      CI: 0.31-1.07). At lower stress levels, no clear associations were observed.
      Regarding subtypes, self-reported stress appeared only to modify the association
      between alcohol intake and ischaemic stroke events. Regarding specific types of
      alcoholic beverages, self-reported stress only modified the associations for
      intake of beer and wine. CONCLUSIONS: This study indicates that the apparent
      lower risk of stroke associated with moderate alcohol consumption is confined to
      a group of highly stressed persons. It is suggested that alcohol consumption may
      play a role in reducing the risk of stroke by modifying the physiological or
      psychological stress response.

PMID- 15956808
TI  - Survival of patients with amyotrophic lateral sclerosis in a population-based
      registry.
AB  - OBJECTIVE: To evaluate the survival of patients with amyotrophic lateral
      sclerosis (ALS) in an Italian population and to assess the effects of selected
      prognostic indicators on survival. BACKGROUND: Median survival of ALS patients
      has been reported to range between 12 and 23 months from diagnosis and between 23
      and 36 months from onset of symptoms. Although several negative prognostic
      factors have been identified, the overall picture still needs clarification.
      METHODS: We included patients enrolled in an Italian ALS Regional Register
      (population 4,529,003) during the calendar year 1998. The diagnosis was confirmed
      by an ad hoc committee using the original El Escorial criteria. Each case was
      regularly followed up until death or December 31, 2002, whichever came first.
      Survival was assessed with the Kaplan-Meier method in the whole sample, by level
      of diagnostic certainty, and by selected prognostic indicators (age, sex, bulbar
      or spinal onset, and disease duration). Multivariate analysis was done with the
      Cox proportional hazard function. RESULTS: The sample comprised 79 patients (33
      female; 46 male) aged 28-85 years (mean age 64.4 years). Onset of symptoms was
      bulbar in 30% of cases. Mean symptom duration at diagnosis was 13.3 months. ALS
      was definite in 43%, probable in 29%, possible in 6%, and suspected in 22%. By
      December 31, 2002, 56 cases (71%) had died. The cumulative probability of
      surviving after diagnosis was 78% at 12 months, 56% at 24 months, and 32% at 48
      months. Median survival from onset was 39.2 months and from diagnosis 30.6
      months. Multivariate analysis confirmed definite ALS at diagnosis and older age
      as adverse prognostic factors. CONCLUSIONS: Survival of ALS patients in the
      present sample was slightly longer than previously reported. Better palliative
      care and supportive treatment may explain the difference. Older age and the
      presence of definite ALS at diagnosis are poor prognostic predictors.

PMID- 15956809
TI  - Case-control study on cellular and cordless telephones and the risk for acoustic
      neuroma or meningioma in patients diagnosed 2000-2003.
AB  - We performed a case-control study on the use of cellular and cordless telephones
      and the risk for brain tumors. We report the results for benign brain tumors with
      data from 413 cases (89% response rate), 305 with meningioma, 84 with acoustic
      neuroma, 24 with other types and 692 controls (84% response rate). For
      meningioma, analogue phones yielded odds ratio (OR) = 1.7, 95% confidence
      interval (CI) = 0.97-3.0, increasing to OR = 2.1, 95% CI = 1.1-4.3 with a >10
      year latency period. Also digital cellular phones and cordless phones increased
      the risk to some extent. For acoustic neuroma, analogue phones gave OR = 4.2, 95%
      CI = 1.8-10 increasing to OR = 8.4, 95% CI = 1.6-45 with a >15-year latency
      period, but based on low numbers. Digital phones yielded OR = 2.0, 95% CI = 1.05
      3.8, whereas for cordless phones OR was not significantly increased. In the
      multivariate analysis, analogue phones represented a significant risk factor for
      acoustic neuroma.

PMID- 15956810
TI  - SLC26A6 and SLC26A7 anion exchangers have a distinct distribution in human
      kidney.
AB  - BACKGROUND: The anion transporters SLC26A6 (PAT1) and SLC26A7, transporting at
      least chloride, oxalate, sulfate and bicarbonate, show a distinct expression and
      function in different mammalian species. They are expressed in kidney, but their
      exact localization in human kidney has not been studied. We therefore examined
      SLC26A6 and A7 expression in human kidneys. METHODS: The localization of SLC26A6
      and A7 in different segments of human nephrons was studied by RT-PCR and
      immunohistochemistry by comparing to the tubular markers PNRA, CD10, Tamm
      Horsfall antigen, high molecular weight cytokeratin, CK7, AQP2 and H(+)V-ATPase.
      RESULTS: In human kidney, SLC26A6 is expressed in distal segments of proximal
      tubules, parts of the thin and thick ascending limbs of Henle's loops, macula
      densa, distal convoluted tubules and a subpopulation of intercalated cells of
      collecting ducts. SLC26A7 is expressed in extraglomerular mesangial cells and a
      subpopulation of intercalated cells of collecting ducts. CONCLUSION: Our results
      show that in human kidney SLC26A6 and A7 have a distinct, partially overlapping
      expression in distal segments of nephrons. The distribution partly differs from
      that found previously in rodent kidneys.

PMID- 15956811
TI  - Natural products and derivatives affecting neurotransmission relevant to
      Alzheimer's and Parkinson's disease.
AB  - The two major neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's
      disease (PD) are characterised by low levels in the brain of the
      neurotransmitters acetylcholine (ACh) and dopamine (DA), respectively. Clinical
      treatment of these two conditions is palliative and relies, in most cases, on
      improving stimulation at the relevant receptors by either increasing levels of
      the endogenous neurotransmitter or by the use of substances which have a similar
      agonist response. Natural products continue to provide useful drugs in their own
      right but also provide templates for the development of other compounds. The
      major advances in the treatment of AD have been the use of acetylcholinesterase
      inhibitors such as galantamine, huperzine A, physostigmine and its derivatives to
      increase the levels of ACh rather than the use of cholinergic compounds, although
      compounds with nicotinic properties have attracted some interest. In contrast,
      the treatment of PD has relied on the elevation of DA levels by use of L-DOPA,
      its precursor, and by the administration of dopaminergic agonists, especially the
      ergot alkaloid derivatives. The use of inhibitors of enzymes that cause breakdown
      of DA is an avenue which is being explored. As well as the major natural products
      of clinical interest, the paper discusses the chemistry, activity and usage of
      the constituents of plants used in traditional medicine for the treatment of
      diseases presenting symptoms similar to those characteristic for Alzheimer's or
      Parkinson's disease.

PMID- 15956812
TI  - Regulation of neuroinflammation by herbal medicine and its implications for
      neurodegenerative diseases. A focus on traditional medicines and flavonoids.
AB  - Herbal medicine has long been used to treat neural symptoms. Although the precise
      mechanisms of action of herbal drugs have yet to be determined, some of them have
      been shown to exert anti-inflammatory and/or anti-oxidant effects in a variety of
      peripheral systems. Now, as increasing evidence indicates that neuroglia-derived
      chronic inflammatory responses play a pathological role in the central nervous
      system, anti-inflammatory herbal medicine and its constituents are being proved
      to be a potent neuroprotector against various brain pathologies. Structural
      diversity of medicinal herbs makes them valuable source of novel lead compounds
      against therapeutic targets that are newly discovered by genomics, proteomics,
      and high-throughput screening.

PMID- 15956813
TI  - Search for natural products related to regeneration of the neuronal network.
AB  - The reconstruction of neuronal networks in the damaged brain is necessary for the
      therapeutic treatment of neurodegenerative diseases. We have screened the neurite
      outgrowth activity of herbal drugs, and identified several active constituents.
      In each compound, neurite outgrowth activity was investigated under amyloid-beta
      induced neuritic atrophy. Most of the compounds with neurite regenerative
      activity also demonstrated memory improvement activity in Alzheimer's disease
      model mice. Protopanaxadiol-type saponins in Ginseng drugs and their metabolite,
      M1 (20-O-beta-D-glucopyranosyl-(20S)-protopanaxadiol), showed potent regeneration
      activity for axons and synapses, and amelioration of memory impairment.
      Withanolide derivatives (withanolide A, withanoside IV, and withanoside VI)
      isolated from the Indian herbal drug Ashwagandha, also showed neurite extension
      in normal and damaged cortical neurons. Trigonelline, a constituent of coffee
      beans, demonstrated the regeneration of dendrites and axons, in addition to
      memory improvement.

PMID- 15956814
TI  - Multifunctional activities of green tea catechins in neuroprotection. Modulation
      of cell survival genes, iron-dependent oxidative stress and PKC signaling
      pathway.
AB  - Many lines of evidence suggest that oxidative stress resulting in reactive oxygen
      species (ROS) generation and inflammation play a pivotal role in the age
      associated cognitive decline and neuronal loss in neurodegenerative diseases
      including Alzheimer's (AD), Parkinson's (PD) and Huntington's diseases. One
      cardinal chemical pathology observed in these disorders is the accumulation of
      iron at sites where the neurons die. The buildup of an iron gradient in
      conjunction with ROS (superoxide, hydroxyl radical and nitric oxide) are thought
      to constitute a major trigger in neuronal toxicity and demise in all these
      diseases. Thus, promising future treatment of neurodegenerative diseases and
      aging depends on availability of effective brain permeable, iron
      chelatable/radical scavenger neuroprotective drugs that would prevent the
      progression of neurodegeneration. Tea flavonoids (catechins) have been reported
      to possess potent iron-chelating, radical-scavenging and anti-inflammatory
      activities and to protect neuronal death in a wide array of cellular and animal
      models of neurological diseases. Recent studies have indicated that in addition
      to the known antioxidant activity of catechins, other mechanisms such as
      modulation of signal transduction pathways, cell survival/death genes and
      mitochondrial function, contribute significantly to the induction of cell
      viability. This review will focus on the multifunctional properties of green tea
      and its major component (-)-epigallocatechin-3-gallate (EGCG) and their ability
      to induce neuroprotection and neurorescue in vitro and in vivo. In particular,
      their transitional metal (iron and copper) chelating property and inhibition of
      oxidative stress.

PMID- 15956815
TI  - Unique properties of polyphenol stilbenes in the brain: more than direct
      antioxidant actions; gene/protein regulatory activity.
AB  - The 'French Paradox' has been typically associated with moderate consumption of
      wine, especially red wine. A polyphenol 3,4',5-trihydroxy-trans-stilbene (a
      member of the non-flavonoids family), better known as resveratrol, has been
      purported to have many health benefits. A number of these valuable properties
      have been attributed to its intrinsic antioxidant capabilities, although the
      potential level of resveratrol in the circulation is likely not enough to
      neutralize free radical scavenging. The brain and the heart are uniquely
      vulnerable to hypoxic conditions and oxidative stress injuries. Recently,
      evidence suggests that resveratrol could act as a signaling molecule within
      tissues and cells to modulate the expression of genes and proteins. Stimulation
      of such proteins and enzymes could explain some the intracellular antioxidative
      properties. The modulation of genes could suffice as an explanation of some of
      resveratrol's cytoprotective actions, as well as its influence on blood flow,
      cell death, and inflammatory cascades. Resveratrol stimulation of the expression
      of heme oxygenase is one example. Increased heme oxygenase activity has led to
      significant protection against models of in vitro and in vivo oxidative stress
      injury. Resveratrol could provide cellular resistance against insults; although
      more work is necessary before it is prescribed as a potential prophylactic in
      models of either acute or chronic conditions, such as stroke, amyotrophic lateral
      sclerosis, Parkinson, Alzheimer, and a variety of age-related vascular disorders.

PMID- 15956816
TI  - Neuroprotective effects of huperzine A. A natural cholinesterase inhibitor for
      the treatment of Alzheimer's disease.
AB  - Huperzine A (HupA), isolated from Chinese herb Huperzia serrata, is a potent,
      highly specific and reversible inhibitor of acetylcholinesterase. It has been
      found to reverse or attenuate cognitive deficits in a broad range of animal
      models. Clinical trials in China have demonstrated that HupA significantly
      relieves memory deficits in aged subjects, patients with benign senescent
      forgetfulness, Alzheimer's disease (AD) and vascular dementia (VD), with minimal
      peripheral cholinergic side effects compared with other AChEIs in use. HupA
      possesses the ability to protect cells against hydrogen peroxide, beta-amyloid
      protein (or peptide), glutamate, ischemia and staurosporine-induced cytotoxicity
      and apoptosis. These protective effects are related to its ability to attenuate
      oxidative stress, regulate the expression of apoptotic proteins Bcl-2, Bax, P53
      and caspase-3, protect mitochondria, and interfere with APP metabolism.
      Antagonizing effects on NMDA receptors and potassium currents may contribute to
      the neuroprotection as well. It is also possible that the non-catalytic function
      of AChE is involved in neuroprotective effects of HupA. The therapeutic effects
      of HupA on AD or VD are probably exerted via a multi-target mechanism.

PMID- 15956817
TI  - Reducing cardiovascular disease in patients with diabetes mellitus.
AB  - PURPOSE OF REVIEW: Patients with diabetes may be considered high-risk for
      management of cardiovascular risk factors not only because of increased rates of
      myocardial infarction but also because of a high prevalence of significant
      subclinical coronary artery disease and a poorer prognosis after myocardial
      infarction. RECENT FINDINGS: Appropriate management of hypertension and
      hyperlipidemia has been shown unequivocally to reduce cardiovascular events.
      Benefit has been demonstrated with multiple antihypertensive agents; however,
      some studies suggest an advantage for angiotensin-converting enzyme inhibitors or
      angiotensin II receptor blockers. Most data for management of lipid disorders in
      diabetes have been obtained using statins; the value of combination lipid
      lowering therapy remains to be validated. SUMMARY: The role of glucose control in
      managing cardiovascular risk in patients with diabetes remains unclear.
      Epidemiologic studies suggest a strong relation between markers of glycemia and
      cardiovascular risk, even extending into the nondiabetic spectrum. Ongoing trials
      are evaluating novel strategies for reducing cardiovascular events in patients
      with diabetes.

PMID- 15956818
TI  - Angiotensin-converting enzyme inhibitors and angiotensin II type I receptor
      blockers in the management of congestive heart failure patients: what have we
      learned from recent clinical trials?
AB  - PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors, angiotensin II
      receptor blockers and aldosterone antagonists have all been shown to decrease the
      morbidity and mortality related to heart failure. The population of patients with
      a diagnosis of heart failure represents a heterogeneous group, ranging from
      asymptomatic left ventricular dysfunction to chronic decompensation with advanced
      heart failure; and the clinical roles of these agents can vary within this
      diverse heart failure population. This article will review the recent
      developments pertaining to renin-angiotensin-aldosterone system modulation
      therapy and help to clarify some of the relevant issues surrounding the role and
      relevance of these drugs in the currently established multi-drug regimen of heart
      failure patients. RECENT FINDINGS: Clinical trials such as OPTIMAAL, VALIANT and
      EPHESUS have added insight into the role of angiotensin II receptor blockers and
      aldosterone in the post-myocardial infarct heart failure patient. The CHARM
      series has provided new information into the role of angiotensin II receptor
      blocker therapy in patients who are angiotensin-converting enzyme intolerant and
      those with heart failure and normal ejection fraction. In addition further data
      is now available about the benefits and risks when considering a strategy of
      either angiotensin-converting enzyme plus angiotensin II receptor blocker or
      angiotensin-converting enzyme plus aldactone in chronic heart failure patients.
      SUMMARY: Important recent clinical trials have helped to add insight on the role
      of renin-angiotensin-aldosterone system in heart failure. Choosing between a
      class of drug or particular strategy depends on knowledge of the patient
      populations studied in clinical trials as well as the inherent risks involved.

PMID- 15956820
TI  - Recent advances in hypertension, stroke, and cardiorenal disease.

PMID- 15956821
TI  - Angiotensin type-2 receptors and cardiovascular function: are angiotensin type-2
      receptors protective?
AB  - PURPOSE OF REVIEW: The renin-angiotensin system is a coordinated hormonal cascade
      of critical importance to the regulation of blood pressure and cardiovascular
      function. The major effector peptide, angiotensin II, binds to two major
      receptors, angiotensin type-1 and angiotensin type-2. Most of the actions of
      angiotensin II are mediated by the angiotensin type-1 receptor, but recent
      evidence strongly suggests that the angiotensin type-2 receptor opposes the
      angiotensin type-1 receptor, particularly by promoting vasodilatation instead of
      vasoconstriction. RECENT FINDINGS: Conclusive evidence has been presented
      indicating that the angiotensin type-2 receptor mediates vasodilatation in small
      resistance arterioles as well as in the coronary microcirculation. Substantial
      evidence also is available that the angiotensin type-2 receptor dilates large
      capacitance vessels, including the aorta, subjected to pressure-overload. The
      angiotensin type-2 receptor has recently been found to inhibit renin biosynthesis
      and secretion similar to the action of the angiotensin type-1 receptor. The
      angiotensin type-2 receptor appears to be cardioprotective, particularly in
      limiting cardiac remodeling following ischemic injury. SUMMARY: The angiotensin
      type-2 receptor represents an important area of cardiovascular investigation with
      potential therapeutic implications for cardiac disease and hypertension.

PMID- 15956822
TI  - Endothelial dysfunction: its role in hypertensive coronary disease.
AB  - PURPOSE OF REVIEW: Coronary artery disease is the major cause of death worldwide.
      Hypertension is a major risk factor for developing coronary disease. It is now
      recognized that endothelial dysfunction is an early marker of coronary artery
      disease before structural changes to the vessel wall are apparent on angiography
      or intravascular ultrasound and that it has a prognostic value in predicting
      cardiovascular events in hypertensive patients. This review addresses recent
      developments in hypertension-induced endothelial dysfunction. RECENT FINDINGS:
      Hyperaldosteronism causes endothelial dysfunction independent of high blood
      pressure. Exaggerated exercise blood pressure response has been related to
      endothelial dysfunction. Cyclosporin-A-induced endothelial dysfunction is related
      to reduced cholesterol content in caveolae. Chronic kidney disease induces
      changes in caveoli-1 and thus contributes to the reduced nitric oxide
      bioavailability, and causes oxidative stress independent of the high blood
      pressure. Asymmetric dimethylarginine plays a role in endothelial dysfunction in
      hypertensive patients independent of insulin resistance. 20
      Hydroxyeicosatetraenoic acid is an independent predictor of hypertension in
      postmenopausal women. Endothelial dysfunction precedes and predicts the
      development of hypertension in postmenopausal women. Oral treatment with L
      arginine improves endothelial dysfunction in hypertensives and lowers the blood
      pressure. SUMMARY: The pathophysiology of endothelial dysfunction in hypertension
      is multifactorial. Recent findings have contributed to our understanding of
      mechanisms of endothelial dysfunction and support a role for early intervention
      to prevent irreversible vascular and organ damage.

PMID- 15956823
TI  - An updated clinical primer on large artery mechanics: implications of pulse
      waveform analysis and arterial tonometry.
AB  - PURPOSE OF REVIEW: The use of pulse wave analysis with arterial tonometry has
      accelerated over the last year. Despite approval from the US Food and Drug
      Administration in 2001 on the use of generalized transfer function to generate
      the central (aortic) pressure wave from the radial waveform, this technique is
      still questioned. This review summarizes major findings on (a) value of arterial
      tonometry in determining indices of cardiovascular function, (b) use of these
      indices in outcome and drug studies, (c) relevance to major trials on blood
      pressure reduction. RECENT FINDINGS: Pulse pressure has emerged as a better
      predictor of cardiac ischemic events than systolic, diastolic, and mean brachial
      pressure. Central systolic and pulse pressure and augmentation index have shown
      an even better relation with cardiovascular events and with outcomes. The claim
      by specific angiotensin-converting enzyme inhibitor and angiotensin receptor
      blocker drugs of their benefits "beyond blood pressure lowering" has been
      challenged on the basis of greater reduction in central and aortic pressure
      compared with brachial pressure measured by cuff sphygmomanometer, as shown by
      the pREterax in regression of Arterial Stiffness in a contrOlled double-bliNd
      study. Augmentation index is higher in hypertension, is inversely related to body
      height, and can be reduced by exercise. Augmentation index shows a linear
      relation with age up to 60 years. Regrettably, recent major trials such as the
      Comparison of Amlodipine versus Enalapril to Limit Occurrences of Thrombosis,
      Prevention of Events with Angiotensin Converting Enzyme Inhibition, and Valsartan
      Antihypertensive Long-term Use Evaluation studies have not included pulse wave
      analysis to distinguish the relative benefit of different drugs. SUMMARY: Pulse
      wave analysis will assist in a better understanding of hypertension as well as in
      establishing the extent of cardiovascular disease and for monitoring therapy.

PMID- 15956824
TI  - Early recognition and treatment of hypertensive heart disease.
AB  - PURPOSE OF REVIEW: Hypertension leads to left ventricular hypertrophy, diastolic
      dysfunction, and eventually clinical heart failure (hypertensive heart disease).
      There is an important need for physicians to recognize this entity, understand
      its pathophysiology, and become fluent in treatment options available. This
      review of recent basic science and clinical data serves to accomplish this task.
      RECENT FINDINGS: In the past year, a number of exciting concepts have come to the
      forefront. First, data on the use of brain natriuretic peptide as a screening
      biomarker has shown promise in patients with symptoms of heart failure. For the
      earliest detection of structural changes, serum propeptide of procollagen type I,
      a marker of the deposition of type I collagen in the cardiac interstitium
      provides a noninvasive way to quantify myocardial fibrosis. Treatment options in
      the past few years have focused heavily on the anti-fibrotic effects of
      inhibitors of the renin-angiotensin-aldosterone system, perhaps supplanting beta
      blockers as first-line agents to regress left ventricular hypertrophy. The
      concept of aldosterone escape is discussed, highlighting the importance of
      aldosterone inhibitors in these patients. Lastly, we provide a comprehensive
      review of all antihypertensive classes and their effects on hypertensive heart
      disease. SUMMARY: The incidence of hypertensive heart disease is increasing.
      Earlier detection may be possible with newly studied serum biomarkers. All anti
      hypertensive treatments have shown improvement in regressing left ventricular
      hypertrophy, but inhibitors of the renin-angiotensin-aldosterone system possess
      the most potent anti-fibrotic effects. It is increasingly important for
      clinicians to identify and manage hypertensive heart disease to prevent increased
      morbidity and mortality.

PMID- 15956825
TI  - Physiologic evidence of renoprotection by antihypertensive therapy.
AB  - PURPOSE OF REVIEW: Hypertension is vastly prevalent worldwide and constitutes the
      second leading cause of end-stage renal disease. Therefore, treating hypertension
      and protecting the kidney from deterioration are exceedingly important. Although
      previous studies have explored the renal effects of various antihypertensive
      drugs in animal models and humans, recent clinical trials are all the more
      convincing. This review summarizes the latest data demonstrating the physiologic
      evidence of renoprotection by antihypertensive therapy. RECENT FINDINGS:
      Experimental studies in various models of hypertension with renal injury have
      demonstrated clearly that angiotensin-converting enzyme inhibitors, angiotensin
      II type 1 receptor blockers, or aldosterone antagonists promote beneficial renal
      actions, through hemodynamic and nonhemodynamic mechanisms. Of particular
      significance, recent clinical trials have demonstrated renoprotection by
      angiotensin II inhibition in patients with hypertension and chronic kidney
      disease. Angiotensin-converting enzyme inhibition and angiotensin II type 1
      receptor blockade have provided equivalent renal benefits, and their dual action
      seems to confer greater renoprotection. The available data on the renal outcomes
      of other antihypertensive drugs such as calcium antagonists have been
      inconsistent. SUMMARY: The results of the numerous experimental and clinical
      studies have established the renoprotective properties of renin-angiotensin
      aldosterone inhibitors, which confer greater benefit by virtue of their effects
      over and beyond blood pressure reduction. These findings provide the convincing
      basis for the recommendation of angiotensin-converting enzyme inhibitors,
      angiotensin II type 1 receptor blockers, or both as first-line therapy in
      hypertension with chronic kidney disease.

PMID- 15956826
TI  - Methods to improve medication adherence in patients with hypertension: current
      status and future directions.
AB  - PURPOSE OF REVIEW: Efficacious pharmacologic treatments are available for the
      management of hypertension, yet only about 50% of patients treated with
      antihypertensive medications have their blood pressure controlled. A key factor
      contributing to poor blood pressure control is suboptimal adherence to prescribed
      therapy. Despite numerous studies conducted over the last 50 years to identify
      the best method for increasing patient compliance, no single intervention has
      emerged as superior to the others. This article reviews the effectiveness of
      methods to improve antihypertensive medication adherence, discusses the effect of
      drug benefit caps on compliance, and proposes a framework for future clinical and
      research directions. RECENT FINDINGS: Several recent systematic reviews and meta
      analyses have attempted to quantify the effectiveness of various methods to
      improve adherence. As a result of the multiple factors influencing medication
      adherence, a patient-centered approach that tailors interventions aimed at
      overcoming barriers to adherence may be necessary. SUMMARY: Physicians and other
      health care professionals should consider nonadherence to medication when
      evaluating a patient with poor blood pressure control. In selecting an
      intervention to improve compliance to medications, clinicians should consider
      engaging the patient in an intervention that overcomes patient-specific barriers.
      Future research should target development of adherence models, which
      simultaneously examine the effects and interactions of social, psychological, and
      biologic variables on antihypertensive medication adherence.

PMID- 15956827
TI  - Drugs in development: targeting high-density lipoprotein metabolism and reverse
      cholesterol transport.
AB  - PURPOSE OF REVIEW: This review summarizes currently available therapies for
      raising high-density lipoprotein cholesterol (HDL-C) and expands on therapies
      currently in development that target high-density lipoprotein cholesterol. RECENT
      FINDINGS: In the realm of new high-density lipoprotein-raising therapies, there
      is a strong focus on high-density lipoprotein metabolism and the reverse
      cholesterol transport pathway. Several infusions of recombinant apoA-I
      Milano/phospholipid complexes appeared to reduce atheroma volume as measured by
      intravascular ultrasound. Both intravenous and oral apoA-I mimetic peptides are
      in early clinical trials. Next generation PPAR-alpha agonists are more potent at
      high-density lipoprotein-raising than currently available fibrates, and dual PPAR
      alpha/PPAR-gamma agonists are under investigation to help correct atherogenic
      dyslipidemia seen in many diabetics. Two small molecule inhibitors of the
      cholesteryl ester transfer protein have shown promise in clinical trials at
      substantially raising high-density lipoprotein cholesterol. SUMMARY: Larger scale
      clinical trials, including those with additional surrogate outcome measures as
      well as cardiovascular event outcomes are needed to further assess the benefit of
      newer high-density lipoprotein-raising therapies. Additional therapeutics are
      currently in development that target other parts of the reverse cholesterol
      transport pathway and, in addition to providing new potential pharmaceuticals,
      will help to further elucidate the atheroprotective mechanisms of high-density
      lipoprotein cholesterol.

PMID- 15956828
TI  - Pharmacologic augmentation of high-density lipoproteins: mechanisms of currently
      available and emerging therapies.
AB  - PURPOSE OF REVIEW: With the limited effects of low-density lipoprotein-based
      lipid intervention, more attention is being paid to drugs that augment or mimic
      high-density lipoprotein's beneficial effects. A thorough understanding of the
      anti-atherogenic effects of high-density lipoprotein, and the mechanisms of
      existing or emerging high-density lipoprotein-based therapies, is essential for
      rational strategy for the prevention of cardiovascular disease. RECENT FINDINGS:
      High-density lipoprotein mediates its beneficial effects through reverse
      cholesterol transport and direct anti-inflammatory effects of apolipoprotein AI
      and other component parts. Currently available drugs increase high-density
      lipoprotein-C through increasing apoAI synthesis (statins, fibrates) and
      decreasing apolipoprotein AI catabolism (niacin). Cholesteryl ester transfer
      protein inhibitors dramatically raise high-density lipoprotein-C, but clinical
      data are still required to verify their cardioprotective effects. Novel therapies
      such as apolipoprotein AImilano, apolipoprotein AI mimetic peptide, and exogenous
      phospholipids show tremendous promise as treatments for atherosclerosis. SUMMARY:
      High-density lipoprotein and its defining functional protein apoAI prevent
      atherosclerosis through reverse cholesterol transport and other direct effects.
      Research has led to the development of novel therapies that increase high-density
      lipoprotein-C or that mimic direct anti-atherogenic effects of apolipoprotein AI.
      As these emerging therapies find a place in clinical medicine, we can anticipate
      preventing a much higher degree of cardiovascular events.

PMID- 15956829
TI  - Low high-density lipoprotein cholesterol disorders and cardiovascular risk:
      contribution of associated low-density lipoprotein subclass abnormalities.
AB  - PURPOSE OF REVIEW: Discuss the contribution of low-density lipoprotein subclass
      abnormalities to cardiovascular risk among individuals with low high-density
      lipoprotein cholesterol levels. RECENT FINDINGS: Low high-density lipoprotein
      cholesterol levels are commonly encountered among patients with early onset
      cardiovascular disease. Most often, a low high-density lipoprotein cholesterol
      level is not an isolated abnormality, but it is usually associated with a number
      of other lipoprotein abnormalities. Data from the Framingham Offspring Study
      demonstrate that among subjects with high-density lipoprotein cholesterol, 1.0
      mmol/L (39 mg/dL), low-density lipoprotein particle numbers were considerably
      higher than indicated by the level of low-density lipoprotein cholesterol because
      these subjects had excess numbers of small cholesterol-depleted low-density
      lipoprotein particles. Elevated numbers of low-density lipoprotein particles
      identify individuals at highest risk for atherosclerotic vascular disease and
      cardiovascular events. SUMMARY: As high levels of low-density lipoprotein
      particles are a robust predictor of cardiovascular events, strategies targeted at
      raising low levels of high-density lipoprotein cholesterol must account for low
      density lipoprotein particle interactions.

PMID- 15956831
TI  - Bibliography. Current world literature. Clinical trials.

PMID- 15956830
TI  - Association between hematological parameters and high-density lipoprotein
      cholesterol.
AB  - PURPOSE OF REVIEW: The ability of high-density lipoprotein cholesterol to reverse
      atherosclerosis and reduce cardiovascular disease has been shown in several
      randomized controlled trials. One mechanism by which high-density lipoprotein
      cholesterol protects the vascular system includes hemorheology, the study of
      blood flow. RECENT FINDINGS: Blood viscosity, or the resistance of flow, can be
      altered by red blood cell aggregation, red blood cell deformability, and plasma
      viscosity. Elevated high-density lipoprotein cholesterol levels may improve all
      of these rheological mediators. An infusion of recombinant high-density
      lipoprotein cholesterol can immediately release nitric oxide, a potent
      vasodilator and responder to changes in rheology, into the arteries by activation
      of endothelial nitric oxide synthase. The stimulation of nitric oxide release by
      high-density lipoprotein cholesterol may also alter blood rheology. SUMMARY: In
      this article, we will review hemorheology, particularly blood viscosity along
      with other hemorheological factors, and examine their association with high
      density lipoprotein cholesterol.

PMID- 15956834
TI  - Classification of the spondyloarthropathies.
AB  - PURPOSE OF REVIEW: The spondyloarthropathies are a group of conditions which
      share similar clinical features. Classification criteria permit separation of the
      conditions, allow better targeting of therapies, better measurement of outcomes,
      and better prognostic information. Early diagnosis remains problematic, but
      validated criteria for established disease are now emerging. RECENT FINDINGS:
      Histopathology and histochemistry are providing a better understanding of the
      underlying process of inflammatory arthritis in spondyloarthropathy and other
      inflammatory arthritides. Early disease, however, continues to challenge current
      criteria. Sophisticated imaging with magnetic resonance imaging is being
      increasingly used and is proving useful for early diagnosis as well as helping to
      understand the pathophysiology of disease. Juvenile idiopathic arthritis
      continues to provide problems and criteria have recently been modified to allow a
      greater clinical utility and inclusion of more patients. Poststreptococcal
      reactive arthritis appears to be a heterogeneous clinical entity, with a group
      looking more like rheumatic fever and a group with spondyloarthropathy traits. It
      may be that the association is not streptococcal, but is a throat infection.
      Currently available criteria for psoriatic arthritis have been evaluated in a
      large cohort. Four of the criteria performed well with high specificity and
      sensitivity whereas the other two had moderate specificity and low sensitivity.
      It was shown that rheumatoid factor positivity does not exclude a diagnosis of
      psoriatic arthritis--the single most important clinical feature of this condition
      being the presence of psoriasis. SUMMARY: The spondyloarthropathy classification
      criteria continue to be an area of development. This is most apparent in juvenile
      arthritis and psoriatic arthritis. The latter is currently undergoing intense
      scrutiny to develop classification criteria and outcome measures.

PMID- 15956835
TI  - Pathogenesis of ankylosing spondylitis and reactive arthritis.
AB  - PURPOSE OF REVIEW: The hallmark of ankylosing spondylitis is acute and chronic
      spinal inflammation initiating in the sacroiliac joints, often coupled with
      enthesitis, presenting as chronic inflammation at the sites of ligamentous and
      tendinous insertions into bone. Peripheral joint synovitis can be a prominent
      feature as well. Reactive arthritis is a sterile synovitis arising after an extra
      articular infection of enteric or urogenital tracts. HLA-B27 has been known for
      about the past 30 years to be associated with ankylosing spondylitis and reactive
      arthritis, but the pathogenesis of ankylosing spondylitis and reactive arthritis
      is still not well defined. Although the clinical manifestations of ankylosing
      spondylitis and reactive arthritis may differ, this update discusses the two
      diseases together and focuses on recent evidence in both. RECENT FINDINGS: With
      respect to HLA-B27 several recent studies address arthritogenic peptides,
      molecular mimicry, and aberrant forms of B27. Several candidate genes in addition
      to B27 have been implicated in recent genetic studies. With respect to bacterial
      infection, recent findings in bacterial antigenicity, host response through
      interactions of antigen-presenting cells, T cells, and cytokines are providing
      new understanding of host-pathogen interactions and the pathogenesis of
      arthritis. Endogenous host factors such as proteoglycans may play a role as
      autoantigens and contribute to chronic inflammation on that basis. SUMMARY:
      Recent advances provide additional new insights into distinct pathogenetic
      mechanisms in AS and ReA that arise from a complex interplay between genetic
      factors including HLA-B27 and environmental factors.

PMID- 15956836
TI  - Pathogenesis of psoriatic arthritis.
AB  - PURPOSE OF REVIEW: Heterogeneity in clinical presentation and disease course has
      hindered understanding of disease mechanisms in psoriatic arthritis, but recent
      studies have provided insights into pathogenesis. This review examines relevant
      animal models and genetic factors implicated in disease susceptibility. Also,
      recent reports on mechanisms related to synovial and entheseal inflammation are
      discussed. RECENT FINDINGS: Two transgenic mouse models (amphiregulin, STAT-3)
      were reported that have features of psoriatic arthritis and psoriasis
      respectively. Genetic studies did not find associations between psoriatic
      arthritis and several class I major histocompatibility complex alleles, the
      caspase-activating recruitment domain 15 domain, or the major histocompatibility
      complex class I chain-related gene A9 allele, in sharp contrast to previous
      reports. The striking association of psoriatic arthritis with mutations in the
      killer immunoglobulin receptors on natural killer cells is particularly exciting
      but needs further study. Psoriatic arthritis has histopathologic features that
      are more characteristic of other forms of spondyloarthritis than rheumatoid
      arthritis. Moreover, several of these features correlate with clinical disease
      activity. Matrix metalloproteinases are strongly expressed in psoriatic arthritis
      synovium, and serum matrix metalloproteinases-3 may be a reliable biomarker for
      monitoring disease response. Finally, the concept of an 'enthesis organ' may
      explain the magnetic resonance imaging findings and clinical signs of psoriatic
      enthesitis and dactylitis. SUMMARY: Recent findings highlight the importance of
      innate immune mechanisms in disease pathogenesis. Moreover, psoriatic arthritis
      and rheumatoid arthritis synovium have divergent histopathologic features that
      indicate distinct disease mechanisms. The generation of appropriate animal models
      coupled with reliable biomarkers will result in a deeper understanding of disease
      pathogenesis and will facilitate the identification of new therapeutic targets.

PMID- 15956837
TI  - Imaging in spondylitis.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe and evaluate recent
      findings with respect to imaging in ankylosing spondylitis. The review includes
      articles from the literature that were published in 2004. RECENT FINDINGS: Three
      types of articles are described: methodological studies aimed at validating
      scoring methods for detecting inflammation and structural damage by plain
      radiography and magnetic resonance imaging, descriptive reviews on imaging in
      ankylosing spondylitis and two studies evaluating miscellaneous aspects of
      imaging. Methodological studies showed promising psychometric properties of
      scoring methods for assessing structural damage of the spine by plain
      radiography, and for assessing inflammation of the spine by magnetic resonance
      imaging. Based on methodological qualifications, a method of preference (the
      modified Stoke ankylosing spondylitis spine score) could be identified for
      assessing 2-year change in structural damage. A number of reviews outlined the
      particular potential of magnetic resonance imaging in evaluating characteristics
      of inflammation and structural changes in ankylosing spondylitis. Two unrelated
      studies showed the potential yields of multidetector computed tomography in
      detecting spinal fractures in ankylosing spondylitis, and of magnetic resonance
      imaging in detecting shoulder problems in ankylosing spondylitis. SUMMARY: MRI
      inflammation may become an important outcome measure in clinical trials in
      ankylosing spondylitis patients, and plain radiography may be used to assess 2
      year progression of structural damage of the spine in ankylosing spondylitis. The
      descriptive reviews may serve as an introduction in the field of imaging in
      ankylosing spondylitis, and the studies on multidetector computed tomography and
      magnetic resonance imaging in shoulder problems may have direct impact for the
      treatment of patients with ankylosing spondylitis in the clinical context.

PMID- 15956838
TI  - Management and treatment of ankylosing spondylitis.
AB  - PURPOSE OF REVIEW: Our purpose is to review the developments in the treatment of
      ankylosing spondylitis in 2004. RECENT FINDINGS: Tumor necrosis factor blockers
      have been shown to have rapid and persistent efficacy with limited additional
      toxicity up to 4 years with continuing therapy, but cessation of therapy results
      in relapse in most patients. Therapy is cost-effective. There are some
      differences between the different tumor necrosis factor blockers currently
      available. Other biologic therapies are not as promising. Algorithms have been
      developed to aid in early diagnosis. This may be relevant for future therapeutic
      strategies. SUMMARY: Tumor necrosis factor blockers are effective and safe in
      active spinal disease, but simple measures such as exercise and nonsteroidal anti
      inflammatory drug therapy are still considered the basis of standard therapy.
      Early disease diagnosis is becoming easier, and is likely to be important for
      optimal therapeutic responses. Future research will include the effect of tumor
      necrosis factor blockade on structural disease progression.

PMID- 15956839
TI  - Psoriatic arthritis therapy advances.
AB  - PURPOSE OF REVIEW: This paper will review the data published in 2004 on the
      treatment of psoriatic arthritis, which arthritis affects 6 to 39% of all
      patients with psoriasis. RECENT FINDINGS: New data from placebo-controlled trials
      of anti-tumor necrosis factor agents, etanercept, infliximab, and adalimumab
      continue to show sustained effectiveness of these therapies in their ability to
      control the symptoms and signs of both arthritis and psoriasis, improve quality
      of life and function, and inhibit disease progression as measured by radiologic
      changes. Medications that inhibit T cells have been approved for the treatment of
      psoriasis and have been studied in psoriatic arthritis. The effectiveness of one
      of these agents, efalizumab, did not achieve statistical significance in the
      treatment of psoriatic arthritis. The results of a trial with a second agent,
      alefacept are pending public review. SUMMARY: There has been a persistent
      increased focus on the diagnosis and treatment of psoriatic arthritis as newer
      and more effective drugs than traditional disease-modifying agents have become
      available.

PMID- 15956840
TI  - Early arthritis and infection.
AB  - PURPOSE OF REVIEW: To summarize the recent literature on the association of
      infection with early arthritis, and to discuss the possible role of such
      infections with respect to the development of chronic rheumatic complications.
      RECENT FINDINGS: Viral infections are frequently associated with arthritis.
      Alphaviruses belong to mosquito-borne viruses, one form of which (Sindbis virus)
      can in Scandinavia and Karelia cause acute arthritis with typical rash. The role
      of this infection leading to chronic erosive arthritis needs further prospective
      studies. Patients infected with HIV can have various forms of arthritis. The role
      of HIV virus as an arthritogenic agent is still debated. On the basis of
      population studies, Campylobacter infections seem to be increasing as causative
      infections in reactive arthritis. There is no role for prolonged antibiotic
      therapy to shorten the duration of acute reactive arthritis, but the possibility
      that such a treatment might reduce the development of chronic sequelae needs to
      be examined in a larger study. The role of preceding infection initiating the
      process of rheumatoid arthritis is still an option, the association being
      observed in about 20% of patients studied in the early phase of arthritis.
      SUMMARY: Viral and microbial infections play a role in acute arthritis. The role
      of these infections in the development of chronic arthritis needs further
      prospective controlled studies.

PMID- 15956841
TI  - Human immunodeficiencies that predispose to intracellular bacterial infections.
AB  - PURPOSE OF REVIEW: Patients treated with anti-tumour necrosis factor agents have
      an increased risk of active tuberculosis. Mycobacteria are bacterial pathogens
      capable of surviving and multiplying within macrophages; these infections are
      characterised by granulomatous inflammation. This review addresses the effects of
      inherited and acquired immunodeficiencies on the susceptibility to the
      development of intracellular bacterial infections. RECENT FINDINGS: Primary and
      secondary immunodeficiencies that result in severely impaired T cell function or
      macrophage activation result in an increased risk of mycobacterial and Salmonella
      infection. Conversely, inherited or acquired antibody or complement deficiency
      does not lead to increased susceptibility to these pathogens. Inherited defects
      in the interleukin-12/interleukin-23-dependent interferon-gamma pathway due to
      mutations in genes encoding the p40 chain common to interleukin-12 and
      interleukin-23, the beta1 chain shared by interleukin-12 and interleukin-23
      receptors, interferon-gamma receptor chains 1 or 2, or signal transducer and
      activator of transcription, predispose to severe infections caused by poorly
      pathogenic mycobacteria and Salmonella species. Acquired defects of cytokine
      function causing increased susceptibility to these pathogens include anti-tumor
      necrosis factor therapy and the generation of interferon-gamma-neutralising
      autoantibodies. Defective nuclear factor kappaB activation caused by hypomorphic
      mutations of the nuclear factor kappaB essential modulator gene, which
      compromises the function of Toll receptors, interleukin-IL receptors, and tumor
      necrosis factor-alpha receptors, also increases susceptibility to severe
      mycobacterial infections. Patients with inherited defects in the phagocyte
      nicotine-adenine dinucleotide phosphate oxidase system are highly susceptible to
      Salmonella infections but only exhibit slightly increased susceptibility to
      mycobacteria. SUMMARY: Collectively, these observations highlight immune
      mechanisms that are essential for protection against intracellular bacteria. This
      information provides clinicians with a framework for investigating patients with
      potentially life-threatening intracellular bacterial infections.

PMID- 15956842
TI  - Extrahepatic manifestations in patients with chronic hepatitis C virus infection.
AB  - PURPOSE OF REVIEW: Chronic hepatitis C virus infection often has autoimmune
      clinical and analytic features. This review analyzes recent data on the close
      association of chronic hepatitis C virus infection with autoimmune and
      lymphoproliferative processes. RECENT FINDINGS: Hepatitis C virus infection has
      been associated with both organ-specific (thyroiditis, diabetes) and systemic
      autoimmune diseases. Experimental, virologic, and clinical evidence has
      demonstrated a close association between hepatitis C virus infection and Sjogren
      syndrome, with hepatitis C virus-associated Sjogren syndrome being
      indistinguishable in most cases from the primary form. With respect to rheumatoid
      arthritis, patients with hepatitis C virus-related polyarthritis and positive
      rheumatoid factor may fulfill the classification criteria for rheumatoid
      arthritis. Hepatitis C virus has also been associated with an atypical
      presentation of antiphospholipid syndrome, as well as with the development of
      sarcoidosis. A higher prevalence of hematologic processes in patients with
      hepatitis C virus infection has recently been reported, including cytopenias and
      lymphoproliferative disorders. Recent data are available on the use of new
      immunosuppressive and biologic agents (mainly mycophenolate mofetil, anti-tumor
      necrosis factor agents, and rituximab) in patients with hepatitis C virus
      infection and autoimmune or lymphoproliferative manifestations. SUMMARY: There is
      increasing evidence of a close association of hepatitis C virus infection with
      autoimmune and hematologic processes. The sialotropism of hepatitis C virus may
      explain the close association with Sjogren syndrome, and its lymphotropism links
      the virus to cryoglobulinemia, autoimmune cytopenias, and lymphoma. The
      substantial overlap between cryoglobulinemic features and the classification
      criteria for some systemic autoimmune diseases (systemic lupus erythematosus,
      rheumatoid arthritis, and polyarteritis nodosa) make the differentiation between
      mimicking and coexistence difficult.

PMID- 15956843
TI  - Diagnosis and epidemiology of osteoporosis.
AB  - PURPOSE OF REVIEW: Osteoporosis remains a major public health problem through its
      association with fragility fractures. Recent data suggest that the annual cost in
      Europe is 13 billion euros, mainly accounted for by hospitalisation after
      fracture. Understanding the epidemiology of osteoporosis is an essential step in
      developing strategies to reduce the burden of osteoporotic fracture in the
      population. RECENT FINDINGS: This article will review recent advances surrounding
      the epidemiology of osteoporosis, the burden of fracture in children and adults
      in this country and abroad, morbidity associated with such fractures,
      associations of disease and medication with fragility fracture, and advances in
      diagnostic techniques and identification of at-risk groups. SUMMARY: The papers
      studied highlight the wealth of high-quality research in this field, and they
      help in the visualisation of strategies to identify individuals at high risk of
      fragility fracture and to quantify fracture risk by measurement of bone density,
      bone quality, and risk factor algorithms.

PMID- 15956844
TI  - The use of bisphosphonates in the treatment of osteoporosis.
AB  - PURPOSE OF REVIEW: The bisphosphonates alendronate and risedronate, given orally
      once weekly, are the cornerstone of treatment of postmenopausal osteoporosis, as
      well as of male and secondary osteoporosis. They reduce significantly the risk of
      vertebral and nonvertebral fractures; their effects appear early, within 6-12
      months, and appear to be sustained. Several questions remain unanswered, however.
      In addition, data on a new bisphosphonate became available in 2004. RECENT
      FINDINGS: The optimal duration of treatment has not been clearly established.
      Long-term data with alendronate are now available, indicating a persistence of
      alendronate effects on bone mineral density and bone turnover markers several
      years after stopping treatment given for 5 years. Whether these effects translate
      into sustained reduction of fractures needs to be further analyzed. Because of
      their efficacy, bisphosphonate use has been explored in other forms of
      osteoporosis, such as after androgen deprivation therapy for prostatic cancer.
      The challenge of long-term compliance with treatment of osteoporosis has
      triggered the use of intermittent bisphosphonate. The effects of intermittent
      oral and intravenous ibandronate on bone mineral density, bone turnover, and
      fractures have been recently reported. SUMMARY: The mechanism by which
      bisphosphonates improve bone strength is not yet fully understood but probably
      involves complex effects on different components of bone strength, such as
      microarchitecture.

PMID- 15956845
TI  - New perspectives on parathyroid hormone therapy.
AB  - PURPOSE OF REVIEW: The prevention and treatment of osteoporosis has traditionally
      involved the use of antiresorptive therapies. The introduction of parathyroid
      hormone, an anabolic agent that enhances bone formation, has been accompanied by
      new treatment strategies. This article reviews combination and sequential therapy
      approaches with parathyroid hormone and antiresorptive agents to optimize
      efficacy outcomes. RECENT FINDINGS: The distinguishing features of the anabolic
      and antiresorptive therapies for the treatment of osteoporosis has led to the
      hypothesis that the appropriate use of both agents, either in sequence or in
      combination, may result in superior fracture protection compared with either
      anabolic or antiresorptive treatment alone. This enthusiasm has been tempered by
      the observations that the transition from daily bisphosphonate therapy may blunt
      the efficacy of teriparatide. By contrast, more recent studies suggest that once
      weekly bisphosphonate therapy may provide a better option with parathyroid
      hormone either in combination or in sequence. These considerations are critical
      to understanding the benefits of sequential treatment (parathyroid hormone
      followed by an antiresorptive agent), which aims to maintain or build on the
      large gains in efficacy from short-term therapy with parathyroid hormone. Because
      patients may require an additional treatment course of parathyroid hormone in the
      future, the choice of antiresorptive agent should be carefully considered. In
      addition, more recent evidence suggests that the forms of parathyroid hormone may
      have important differences in action that influence combination and sequence
      outcomes. SUMMARY: Combination and sequential therapy with parathyroid hormone
      offers new options to maximize efficacy in patients at risk for osteoporotic
      fracture.

PMID- 15956846
TI  - Genetic determinants of osteoporosis.
AB  - PURPOSE OF REVIEW: Osteoporosis is a common disease with a strong genetic
      component characterised by reduced bone mass and an increased risk of fragility
      fractures. Several advances have been made over recent years in understanding the
      genetic basis of susceptibility to osteoporosis. This paper will review recent
      developments in this area. RECENT FINDINGS: Twin studies have shown that genetic
      factors contribute to osteoporosis by influencing bone mineral density and other
      determinants of fracture risk such as ultrasound properties of bone, skeletal
      geometry, and bone turnover. In the normal population, many different genes
      contribute to the regulation of these phenotypes by interacting with
      environmental factors such as diet and exercise. Whereas the effect size of
      individual genes is small, meta-analysis has been successfully used in many cases
      to define the role of individual polymorphisms in predisposing to osteoporosis.
      Linkage studies in humans and experimental animals have identified several
      quantitative trait loci that regulate osteoporosis-related phenotypes, and many
      genes that cause monogenic bone diseases have been identified by use of this
      approach. It has been found that subtle polymorphisms in some of these genes also
      contribute to regulation of bone mass in the normal population. SUMMARY: Research
      has recently begun to clarify the genes and genetic variants that predispose to
      osteoporosis and regulation of bone mass. Clinical applications of this research
      include the identification of genetic markers for assessment of fracture risk and
      the identification of novel molecular targets for the design of drugs that can be
      used to treat bone disease.

PMID- 15956847
TI  - Bibliography. Current world literature. Spondyloarthropathies.

PMID- 15956848
TI  - Exciting new research on recruitment and retention.

PMID- 15956850
TI  - United Ostomy Association provides help for ostomy patients and caregivers.

PMID- 15956851
TI  - Ethical support for culturally sensitive health care.
AB  - This month's column presents a case study of a Muslim patient and the
      considerations for culturally sensitive care that one nurse implemented. The
      interventions resolved potential cultural conflict and involved several
      departments within her agency. A brief review of the deliberations and decisions
      of the Institutional Ethics Committee identifies the supporting ethical arguments
      and the recommendations for developing cultural sensitivity within its healthcare
      organizations.

PMID- 15956852
TI  - What's the QT on the QT?: identifying torsades de pointes.

PMID- 15956853
TI  - How you can participate in advancing geriatric home care practice.

PMID- 15956854
TI  - The Medicare drug card.

PMID- 15956855
TI  - The importance of work environment: evidence-based strategies for enhancing nurse
      retention.
AB  - As the nation faces a growing nursing shortage, it is imperative that home care
      leaders implement evidence-based strategies to improve nurse recruitment and
      retention. Previous research indicates that characteristics of the work
      environment that support nursing practice enhance nurses' job satisfaction and
      reduce turnover. Yet, there is little evidence to assist in prioritizing
      initiatives to improve the work environment of nurses. In this nationwide survey,
      home care nurses were asked to rate the importance of specific agency work
      environment traits, as listed on the Nursing Work Index-Revised, in supporting
      their home care practice. The 10 agency traits rated as most important are
      presented, and evidence-based recommendations for creating a culture of nurse
      retention are discussed.

PMID- 15956856
TI  - Factors attracting and keeping nurses in home care.
AB  - The nursing shortage relates not only to recruiting nurses into the profession
      but also retaining nurses in practice. Although several studies have examined
      nurse retention in general, few have addressed retention as a home care issue.
      This descriptive study identifies factors that attracted nurses to home care and
      factors that contributed to job satisfaction and dissatisfaction in the state of
      Connecticut. These findings provide insights to home care agencies on issues that
      should be addressed to reduce turnover and improve retention in home care.

PMID- 15956857
TI  - Exercise of autonomous home care practice: the relationship with nurse
      characteristics.
AB  - This study examined how the value of autonomy is reflected in home healthcare
      agencies' practice models and how staff registered nurse (RN) characteristics
      (education, experience, certification) relate to the RNs' perception of their
      ability to exercise autonomous practice: control over practice decisions
      (clinical autonomy) and control over practice setting decisions (organizational
      autonomy). RNs (N = 82) from 11 agencies were found to have more control over
      practice decisions than practice setting decisions. No significant relationship
      was found between RN characteristics of education, RN experience, home healthcare
      experience, and specialty certification.

PMID- 15956859
TI  - The use of 'as-needed' range orders for opioid analgesics in the management of
      acute pain: a consensus statement of the American Society for Pain Management
      Nursing and the American Pain Society.
AB  - The use of "as-needed" or "PRN" range orders for opioid analgesics in the
      management of acute pain is a common clinical practice. This approach provides
      flexibility in dosing to meet individual patients' unique analgesic requirements.
      Range orders enable necessary and safe dose adjustments based on an individual's
      response to treatment. This paper presents the consensus statement of the
      American Society for Pain Management Nursing and the American Pain Society on the
      use of "as-needed" range orders for opioid analgesics in the management of acute
      pain.

PMID- 15956861
TI  - New dietary guidelines to help Americans make better food choices and live
      healthier lives.

PMID- 15956862
TI  - Selecting effective instructional resources.

PMID- 15956863
TI  - The "what it means" section in home health compare is not a realistic review of
      agency quality.

PMID- 15956864
TI  - The Journal of Developmental and Behavioral Pediatrics and the Society for
      Developmental and Behavioral Pediatrics.

PMID- 15956865
TI  - Two approaches to maternal depression screening during well child visits.
AB  - The US Preventive Services Task Force (USPSTF) has recommended depression
      screening for adults. Screening mothers has special importance to pediatricians
      because of the impact of maternal depression on children. The two screening
      questions endorsed by the USPSTF may allow pediatricians to screen mothers during
      routine well child care. This study explores the feasibility and yield of
      interview- and paper-based pediatric screening for maternal depression during
      well child visits. A structured interview script was developed to inquire about
      maternal depression. It included the two-question screen and required less than 1
      minute to administer. An alternative paper-based screen asked the two questions
      after a brief written introduction providing the rationale. Four community
      pediatric practices in New Hampshire and Maine were trained in both screening
      approaches and developed plans on how to respond to positive screens (either
      question positive). The 11 providers at these sites tested the two approaches on
      two different series of mothers at well child visits. The pediatricians also
      reported barriers to the screening inquiries, maternal responses, and subsequent
      clinician actions and referrals. The pediatricians screened 250 mothers via the
      scripted interview. In a second trial, 223 women had paper-based depression
      screening. Yields from the paper-based screen were 22.9% versus 5.7% for the
      interview-based screener. Pediatricians also took on the new role of discussion
      of possible depression in about two thirds of cases. Subsequently, 7.6% of all
      women with paper-based screening were referred to mental health versus 1.6% with
      the interview-based screening. With the interview, mothers of children younger
      than 1 year of age were less likely to screen positive than those with older
      children (1.9% vs. 8.5%, p = .04). With the paper-based screener, no age
      differences in positive screen rates occurred. While both approaches to screening
      were feasible in primary care, the yield from the two different approaches
      differed substantially. This finding deserves exploration in future studies. With
      either of these screening approaches, pediatricians could enhance their detection
      of mothers at risk of depression. The outcomes of pediatrician screening and the
      best approach to follow-up care still need to be determined.

PMID- 15956866
TI  - The physical, developmental, and mental health needs of young children in child
      welfare by initial placement type.
AB  - The American Academy of Pediatrics recommends comprehensive assessments for
      children entering foster care. These children may be placed with biological
      parents, kin, or in nonrelative foster care. It is not known whether health
      related needs differ by placement. Chart abstractions were conducted of child
      welfare and medical records of 1542 children, ages 3 months to 5 years 11 months,
      admitted to San Diego's sole emergency shelter/receiving facility from April 1,
      1998, through June 30, 1999, for investigation of alleged maltreatment. Children
      were discharged to three placement types: biological parents (28.5%), kinship
      caregivers (28.4%), or nonrelative foster parents (43.1%). Overall, 86.7% of
      children studied demonstrated physical, developmental, or mental health needs,
      with more than half displaying two or more problems. More than half of the
      children had a "Suspect" score on the Denver-II; 70.3% of children with "Suspect"
      scores were found to have delay on a developmental evaluation. Almost one tenth
      of the sample were diagnosed with one or more mental health conditions. Few
      differences were found for physical, developmental, or mental health concerns by
      placement. Results suggest that young children placed with biological parents or
      in kinship care have similar needs to those of children placed with foster
      parents. This study confirms the importance of comprehensive assessments for
      young children removed from their homes, regardless of placement. It also
      illustrates a need for standardized assessment criteria, particularly for
      developmental and mental health status, and for collaborative care models for all
      young children entering the child welfare system, regardless of their placement
      following investigation.

PMID- 15956867
TI  - Situational analysis of dietary challenges of the treatment regimen for children
      and adolescents with phenylketonuria and their primary caregivers.
AB  - A situational analysis was conducted to evaluate challenges with the treatment
      regimen (a low protein diet and special supplemental formula) for children and
      adolescents with phenylketonuria (PKU) and their caregivers. A semistructured
      interview was administered to 19 caregivers and 11 children with PKU to describe
      formula and dietary problems and their frequency, difficulty, and affective
      intensity. Information was also gathered on attempted solutions to problems and
      their perceived effectiveness. Caregivers who rated dietary problems as less
      frequent, difficult, and emotionally upsetting and strategies as more effective
      for solving problems had children with significantly lower phenylalanine (Phe)
      levels, a biological indicator of adherence (i.e., better adherence; all p values
      <.05). Caregivers who reported using strategies coded as representing an
      authoritarian parenting style to solve dietary problems were significantly more
      likely to have lower household incomes and older children with higher Phe levels
      than were those who did not report such strategies (all p values <.05).

PMID- 15956868
TI  - Effects of prenatal cocaine/polydrug use on maternal-infant feeding interactions
      during the first year of life.
AB  - The effects of prenatal cocaine use on quality of maternal-infant interactions
      were evaluated using the Nursing Child Assessment Feeding Scale (NCAFS). A total
      of 341 (155 cocaine using; 186 non-cocaine using) low socioeconomic, primarily
      African-American dyads were evaluated longitudinally at birth, 6.5, and 12
      months. Group differences over time were examined, controlling for covariates,
      using a mixed-model linear approach. Women who used cocaine during pregnancy were
      less sensitive to their infants than non-cocaine-using women at 6.5 and 12
      months. At 6.5 months, heavier prenatal cocaine users were less responsive to
      their infants than lighter users. In infants, prenatal cocaine exposure was
      related to poorer clarity of cues. There were no significant cocaine effects on
      maternal social-emotional growth fostering, cognitive growth fostering, or infant
      responsiveness to mother. Controlling for covariates, concentration of cocaine
      metabolites predicted maternal sensitivity to infant cues and infant clarity of
      cues at 1 year. Maternal cocaine use during pregnancy and other pre- and
      postnatal factors adversely affect maternal-infant interactions during the first
      year of life.

PMID- 15956869
TI  - Attention on inattention: the differential effect of caregiver education on
      endorsement of ADHD symptoms.
AB  - The impact of caregiver education level on endorsement of attention-deficit
      hyperactivity disorder (ADHD) symptoms for inattention (IA) and hyperactivity
      compulsivity (HA) in a sample of high-risk youths was examined. Participants were
      1347 caregivers of varying educational backgrounds who completed the ADHD module
      of the Diagnostic Interview Schedule for Children IV. The relationship of
      caregiver education to ADHD symptom endorsement was examined in three sets of
      analyses in which IA and HA symptoms were simultaneously regressed on caregiver
      years of education. Both multivariate analysis of covariance and logistic
      regression analyses revealed significantly lower rates of IA symptom endorsement
      by caregivers with less education, while there was no effect for HA symptoms. A
      multiple indicator multiple cause (MIMIC) model analysis also revealed that
      caregiver years of education was significantly positively associated with IA but
      not with HA symptoms, even when other demographic factors were controlled. There
      is a clear effect of caregiver education on ADHD symptom endorsement patterns,
      raising concerns that demographic factors related to symptom measurement may
      contribute to discrepancies in the assessment and treatment of ADHD.

PMID- 15956871
TI  - Emotional regulation and its impact on development in extremely low birth weight
      infants.
AB  - The purposes of this study were to compare the Bayley Scales of Infant
      Development (BSID-II) scores at 8 and 18-22 months adjusted age of a cohort of 47
      extremely low birth weight infants and to determine whether there was an
      association between changes in test scores and infant behavior as measured by the
      Behavioral Rating Scale of the BSID-II at 18-22 months adjusted age. Psychomotor
      Developmental Index scores did not differ between the two testing points (p =
      .17), whereas the Mental Developmental Index (MDI) scores dropped significantly
      (p = .006). Emotional regulation and low household income were both significantly
      associated with changes in MDI scores (p = .001 and p = .002, respectively).
      After adjusting for household income, the association between emotional
      regulation and changes in MDI scores remained significant (p = .02). Results
      suggest that infant behavioral characteristics, as well as family socioeconomic
      status, can adversely affect developmental outcome at 18-22 months adjusted age.

PMID- 15956873
TI  - Behavioral genetics and child temperament.
AB  - Most temperament theories presume a biological basis to those behavioral
      tendencies thought to be temperamental in origin. Behavioral genetic methods can
      be used to test this assumption. Twin and adoption studies suggest that
      individual differences in infant and child temperament are genetically
      influenced. However, behavioral genetics has much more to offer to the study of
      temperament than simple heritability estimates. The present paper describes some
      recent findings from behavioral genetics research in temperament that go well
      beyond the basic nature-nurture question. These findings include the importance
      of nonshared environmental influences on temperament, genetic continuity and
      environmental change during development, links between temperament and behavior
      problems, and harnessing the power of molecular genetics to identify specific
      genes responsible for genetic influence on early temperament.

PMID- 15956875
TI  - Lesbian mothers, gay fathers, and their children: a review.
AB  - There is a variety of families headed by a lesbian or gay male parent or same-sex
      couple. Findings from research suggest that children with lesbian or gay parents
      are comparable with children with heterosexual parents on key psychosocial
      developmental outcomes. In many ways, children of lesbian or gay parents have
      similar experiences of family life compared with children in heterosexual
      families. Some special considerations apply to the context of lesbian and gay
      parenting: variation in family forms, children's awareness of lesbian and gay
      relationships, heterosexism, and homophobia. These issues have important
      implications for managing clinical work with children of lesbian mothers or gay
      fathers.

PMID- 15956876
TI  - Self-injury and mental retardation in a 7-year-old boy.

PMID- 15956879
TI  - The future of developmental behavioral pediatrics.

PMID- 15956880
TI  - Hospital resource utilization in childhood cancer.
AB  - To describe the patterns and predictors of hospital resource utilization in a
      cohort of children with newly diagnosed cancer, a retrospective cohort study of
      195 consecutively diagnosed children with cancer at a single large Midwestern
      children's hospital was conducted. Patients were diagnosed between November 1995
      and March 1997. All hospital encounters for these patients starting from the time
      of diagnosis to 3 years from diagnosis were identified using hospital
      administrative data. The patients were categorized into four diagnostic groups:
      lymphoid malignancies (acute lymphoblastic leukemia and lymphoma), myeloid
      leukemias (acute myeloid leukemia and chronic myeloid leukemia), central nervous
      system tumors, and solid tumors. Hospital charges and length of stay for patients
      in each diagnostic category were described. Predictive models for total resource
      consumption (total hospital charges) and intensive care use were derived. One
      hundred sixty-five of the 195 were admitted to Riley Hospital for Children at
      least once during the 3-year period following diagnosis. Among these 165, mean
      age at diagnosis was 6.9 years (minimum newborn, maximum 18.7 years). The ratio
      of boys to girls was 99:66 (1.5:1). The distribution of 165 diagnoses was as
      follows: 65 (39%) with lymphoid malignancy, 13 (8%) with myeloid leukemia, 36
      (22%) with central nervous system tumors, and 51 (31%) with solid tumors. Sixty
      two patients (38%) used the pediatric intensive care unit (PICU) at least once;
      22 patients (13%) underwent stem cell transplantation. Sixty-five patients (39%)
      entered clinical trials. One hundred thirty-nine patients (84%) were alive at the
      end of 3 years. Three-year cumulative hospital charges were USD 16 million-
      almost USD 100,000/child hospitalized. Half of these charges were incurred in the
      first 4.5 months after diagnosis. Half of all hospital charges accrued to only
      12.7% of patients; these patients were more likely to have a diagnosis of myeloid
      leukemia, to have undergone stem cell transplantation, and to have used the PICU.
      There were three independent predictors of hospital charges (log transformed):
      stem cell transplantation, PICU utilization, and death within 3 years of
      diagnosis. PICU utilization was predicted by tumor type (myeloid leukemia and
      central nervous system tumors were positive predictors of PICU utilization;
      lymphoid malignancy and solid tumors were negative predictors), stem cell
      transplantation, and death within 3 years of diagnosis. The authors conclude that
      hospitalization for childhood cancer is common, costly in the short term, and to
      some extent predictable. These data suggest that failures of current treatment
      not only lead to death but also add significantly to hospital resource
      utilization.

PMID- 15956881
TI  - Immunohistochemical detection of the apoptosis-related proteins FADD, FLICE, and
      FLIP in Langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is characterized by an accumulation of
      dendritic Langerhans cells in granulomatous lesions in various organs. The
      etiology of LCH remains enigmatic. Fas/APO-1/CD95 belongs to the "death receptor"
      family of apoptosis regulators and has been implicated in the downregulation of
      immune responses. The authors examined the expression of three proteins that are
      engaged in the Fas signaling cascade-FADD/Fas-associated death domain-containing
      protein, FLICE/FADD-like interleukin-1beta-converting enzyme (both pro
      apoptotic), and FLIP/FLICE-inhibitory protein (anti-apoptotic)-in lesions from
      LCH patients. Immunohistochemistry was performed on paraffin-embedded tissue
      specimens from 43 children with LCH. The infiltrates were scored according to the
      amount of positive pathologic Langerhans cells (pLCs). In all investigated
      specimens, the majority of the pLCs expressed FADD, active FLICE, and FLIP. The
      clinical outcome of the disease could not be correlated to the expression of the
      investigated proteins. This study shows a high expression of the apoptosis
      related proteins FADD, active FLICE, and FLIP in pLCs. The authors previously
      showed that pLCs express Fas and Fas ligand. Taken together, these findings
      suggest that the Fas signaling pathway may be involved in the pathogenesis of
      LCH.

PMID- 15956882
TI  - Prospective evaluation of clinical and laboratory effects of intrathecal
      chemotherapy on children with acute leukemia.
AB  - The objective of this prospective 18-month study was to evaluate the clinical and
      laboratory effects of repeated intrathecal injections of chemotherapy in children
      with acute leukemia. All procedures were performed under general anesthesia, and
      complications were prospectively recorded. Laboratory measurements included
      lumbar puncture opening pressure, cerebrospinal fluid (CSF) chemistry, and cell
      count and morphology. Central venous pressure and ophthalmologic examinations
      were also performed. Forty-seven children underwent 247 intrathecal injections of
      chemotherapy. Adverse effects (13.7% of the procedures) included nausea and
      vomiting, back pain, and headache. One child each had transient cauda equina
      syndrome, transient communicating hydrocephalus, and persistent sacral plexus
      injury. The mean lumbar puncture opening pressure was significantly higher after
      intrathecal therapy than before (22 +/- 8 vs. 15 +/- 9 cm H2O, P = 0.02) and
      higher than reported in age-matched children without leukemia. All CSF
      chemistries, cell count, and morphology were normal. The overall incidence of
      complications was 13.7%. Most were mild and resolved quickly, but significant
      neurologic complications did occur. Lumbar puncture opening pressure was
      significantly higher in children with acute leukemia after intrathecal
      chemotherapy.

PMID- 15956883
TI  - CT-estimated volume of Wilms tumor can predict weight.
AB  - Wilms tumor weight was used to recruit patients in a recent National Wilms Tumor
      Study (NWTS) group trial. The authors hypothesized that a simple calculation of
      tumor volume based on a preoperative CT scan could predict tumor weight. The
      authors reviewed charts and CT images of patients with Wilms tumors who were
      treated at their institution between 1985 and 2002. Tumor volume was calculated
      as: V = 1/6pi x d (long axis) x d (short axis) x d (craniocaudal). Weight and
      calculated tumor volume were correlated using linear regression. Complete data of
      tumor weight and volume could be determined in 25 of the 49 patients. These were
      highly correlated (Spearman R = 0.97). Wilms tumor weight can be predicted based
      on a simple estimate of tumor volume on a preoperative CT scan. CT-estimated
      volume may replace weight as a prognostic factor and in guiding management.

PMID- 15956884
TI  - Height as a risk factor for osteosarcoma.
AB  - Previous investigations have suggested that osteosarcoma may be associated with a
      taller stature, but the relationship between height and osteosarcoma remains
      controversial. Height at diagnosis was evaluated in a continuous series of 962
      osteosarcoma subjects treated between 1981 and 2001. Patients diagnosed during
      growth (group 1) were separated from those diagnosed in adulthood (group 2).
      Height (H) and final height (FH) were expressed as standard deviation scores
      (SDS), calculated by national reference data. Group 1 subjects were above the
      50th centile and their mean H-SDS values (0.31 +/- 1.1) were significantly higher
      than the mean FH-SDS values (P < 0.0001) of the group 2 subjects, both in males
      and females. In contrast, the mean FH-SDS (0.01 +/- 1.1) of group 2 did not
      differ from that of the reference population. The highest incidence of
      osteosarcoma was at 12.5 years in females, 14.5 years in males. These data
      confirm previous observations of an association between osteosarcoma development
      and height, at least in growing individuals. The higher incidence during the
      pubertal spurt, in the anatomic sites of greater growth and in taller
      individuals, suggests that growth factors play an important role in the
      pathogenesis of this bone cancer.

PMID- 15956885
TI  - Management of asymptomatic anthracycline-induced cardiac damage after treatment
      for childhood cancer: a postal survey among Dutch adult and pediatric
      cardiologists.
AB  - Asymptomatic anthracycline-induced cardiac damage (A-CD) is a serious problem
      among young childhood cancer survivors. The aim of this survey was to assess the
      current treatment policy in these patients in the Netherlands. A questionnaire
      was sent to all 136 departments of adult or pediatric cardiology in the
      Netherlands. It was returned by 61% of the departments. Sixty-six percent of the
      respondents started medical treatment (ie, an ACE inhibitor and/or a beta
      blocker) in childhood cancer survivors with asymptomatic A-CD. Fifty-eight
      percent of the respondents indicated that their treatment decision was based on
      published findings in the literature, but none of them referred to studies
      evaluating the treatment of asymptomatic A-CD. A majority of adult and pediatric
      cardiologists started medical treatment in childhood cancer survivors with
      asymptomatic A-CD without knowledge of the benefits and risks of treatment in
      this patient group. Before ACE inhibitors and/or beta-blockers can be recommended
      as routine practice in childhood cancer survivors with asymptomatic A-CD,
      randomized controlled trials should be performed. Until then, the authors
      recommend centralizing the treatment of childhood cancer survivors with
      asymptomatic A-CD in a specialized center to cluster the available knowledge and
      experience.

PMID- 15956886
TI  - Platelet function disorder in Gardner-Diamond syndrome: a case report and review
      of the literature.
AB  - The Gardner-Diamond syndrome is a disorder characterized by recurrent spontaneous
      painful bruising in patients with underlying psychosis and neurosis. Despite the
      presence of other symptoms suggestive of an underlying disorder of primary
      hemostasis in a large percentage of reported patients, results of testing for von
      Willebrand disease or platelet function disorders are lacking. The authors
      describe a case of Gardner-Diamond syndrome in an adolescent girl who had
      abnormal platelet responses during platelet aggregation studies. A review of the
      literature revealed only three additional patients with Gardner-Diamond syndrome
      who have had platelet aggregation studies reported. To date, all patients with
      Gardner-Diamond syndrome reported to have undergone platelet aggregation studies
      have had abnormal results.

PMID- 15956887
TI  - The use of high-dose daily cabergoline in an adolescent patient with
      macroprolactinoma.
AB  - Prolactinomas are rare in children and adolescents but well studied in adults.
      Dopamine agonists are the treatment of choice for all ages. Bromocriptine is the
      only agonist approved for use in pediatric patients by the FDA. Cabergoline, a
      second-generation ergot derivative with a longer half-life, has been used in
      resistant prolactinomas and as first-line treatment in adults. The authors
      describe an adolescent boy with a pituitary macroadenoma with an initial
      prolactin level of 73,777 ng/mL. After failing to respond to bromocriptine and
      standard-dose cabergoline, he responded well to very high daily doses of
      cabergoline (1.5 mg daily), with a current prolactin level of 726 ng/mL and
      notable reduction in tumor size. Escalating doses of cabergoline should be
      considered in pediatric patients with dopamine-resistant prolactinomas.

PMID- 15956888
TI  - DDAVP-induced hyponatremia in young children.
AB  - Desmopressin (DDAVP) is used to improve hemostasis in patients with bleeding
      disorders. The side effects of DDAVP in adults and children are benign. However,
      there has been concern regarding the development of hyponatremia and seizures
      after the use of DDAVP in young children. The authors describe three children
      under 3 years of age who developed hyponatremia (two also developed seizures)
      following intravenous administration of DDAVP at a standard dose of 0.3 mug/kg.
      Fluid restriction, avoidance of hypo-osmolar fluid, and close monitoring of fluid
      and electrolytes for 12 to 24 hours after the administration of DDAVP in children
      younger than 3 years of age is recommended.

PMID- 15956889
TI  - Classic transient erythroblastopenia of childhood with human parvovirus B19
      genome detection in the blood and bone marrow.
AB  - The etiology of transient erythroblastopenia of childhood (TEC) remains unknown,
      although an association with viral infections has been proposed. The authors
      describe a 3.5-year-old girl with classic TEC concomitantly with human parvovirus
      B19 (HPV) infection. The infection was evident by detection of HPV genome in the
      blood and the bone marrow by polymerase chain reaction. Viral genome was no
      longer detected when the TEC resolved clinically. The patient was immunocompetent
      and the anemia has not recurred. To the authors' knowledge, this is one of the
      few documented cases of classic TEC attributable to HPV infection.

PMID- 15956890
TI  - Kikuchi-Fujimoto disease is a rare cause of lymphadenopathy and fever of unknown
      origin in children: report of two cases and review of the literature.
AB  - Kikuchi-Fujimoto disease, a benign and unusual self-limiting histiocytic
      necrotizing lymphadenitis of unknown origin, should be included in the
      differential diagnosis of lymphadenopathy and fever of unknown origin. This
      disease mostly affects young Asian women and has rarely been reported in
      children, thus remaining a poorly recognized entity that is frequently confused
      with malignant lymphoma. The authors describe two children with Kikuchi-Fujimoto
      disease, with particular attention to diagnostic approach and clinical and
      histologic features of the disease.

PMID- 15956891
TI  - Late presentation of opsoclonus-myoclonus-ataxia syndrome in a child with stage
      4S neuroblastoma.
AB  - Opsoclonus-myoclonus-ataxia syndrome (OMA) in children is most commonly
      associated with occult neuroblastoma (NB). Although children with OMA and NB have
      decreased mortality, they suffer from increased neurologic morbidity. The
      pathogenesis of OMA in NB is not well understood, but current research and
      treatments support an immune-mediated process. The authors describe an unusual
      presentation of OMA occurring following 6 months of chemotherapy in a child with
      stage 4S NB who presented with partial Horner syndrome. Histopathologic
      examination of his primary cervical tumor showed NB maturation, which may have
      played a role in precipitating OMA syndrome. Further study of unusual cases of
      OMA in NB may provide better understanding of the syndrome and additional
      treatment options for these children.

PMID- 15956892
TI  - Multifocal osteochondroma after repeated irradiation in a boy with Hodgkin
      disease.

PMID- 15956893
TI  - Complete evidence regarding major vascular injuries during laparoscopic access.
AB  - Recent reports by the Australian Safety and Efficacy Register for New
      interventions and Procedures (ASERNIP-S) and the Royal Australian and New Zealand
      College of Obstetricians and Gynaecologists (RANZCOG) concluded that insufficient
      evidence is available to assess the safety of the open versus closed laparoscopy
      in regard to major vascular and visceral injuries. The aim of this study was to
      assess the relative safety of open and closed laparoscopy with respect to rates
      of major vascular and visceral injuries. A combined prospective/retrospective
      review of a single-surgeon series of 5900 open laparoscopies was performed. A
      meta-analysis of all reported series of open and closed laparoscopy was conducted
      using PubMed and MEDLINE search engines to compare major vascular and visceral
      injury rates. Medicolegal and manufacturer device reports were also reviewed. The
      case series of 5900 open laparoscopies reported a single visceral injury and no
      major vascular injuries. The meta-analysis revealed 336 major vascular injuries
      in 760,890 closed laparoscopies, a mean rate of 0.044%, 1 injury per 2272 cases,
      compared with 0 injuries in 22,465 open laparoscopies (P = 0.003). Visceral
      injuries occurred more frequently, 515 injuries in 760,890 closed laparoscopies
      (mean rate, 0.07) and 11 injuries in 22,465 open laparoscopies (mean rate, 0.05;
      P = 0.18). Medicolegal and device reports revealed a further 647 major vascular
      injuries and 500 major visceral injuries. In contrast to the conclusion formed by
      the RANZCOG and ASERNIP-S, the available evidence shows that open laparoscopy
      eliminates the risk of major vascular injury and reduces the rate of major
      visceral injuries. Open laparoscopy using the Hasson cannula should be the
      preferred method of peritoneal access.

PMID- 15956894
TI  - Inflammatory response of interleukin-1beta and interleukin-6 in septic rats
      undergoing laparotomy and laparoscopy.
AB  - It is generally accepted that greater inflammatory response is observed after
      laparotomy than laparoscopy in animal models. However, in a previous study, we
      reported there are no significant differences in the systemic response of tumor
      necrosis factor (TNF)-alpha between the laparotomy and laparoscopy groups in a
      rat model of endotoxic shock. The present study extends this investigation to the
      inflammatory response of 2 additional proinflammatory mediators, interleukin (IL)
      1beta and IL-6, in septic rats after laparotomy and laparoscopy in the same
      animal model. Rats received lipopolysaccharide (LPS) intraperitoneally and
      underwent laparotomy (n = 5), laparoscopy (n = 5), or no surgical intervention (n
      = 5). A control group received anesthesia only (n = 5). Serum IL-1beta and IL-6
      levels were significantly higher at 2, 4, and 8 hours after LPS injection and
      were equally suppressed in the laparotomy and laparoscopic groups (P < 0.05).
      Liver IL-1beta mRNA and protein levels were significantly inhibited at 2, 4, and
      8 hours in the laparotomy and laparoscopic groups. Liver IL-6 mRNA (2 and 4
      hours) and protein (4 hours) levels were also suppressed significantly in both
      the laparotomy and laparoscopic groups (P < 0.05). There were no significant
      differences in hepatic levels of mRNA and protein of IL-beta and IL-6 in both the
      laparotomy and laparoscopic groups. These results extend our previous finding
      demonstrating the suppression of TNF-alpha in both the laparotomy and
      laparoscopic groups. The behavior of the markers used in our study demonstrated
      that the inflammatory response does not differ between laparotomy and
      laparoscopic surgery in our rat model of endotoxic shock.

PMID- 15956895
TI  - Long-term outcomes of laparoscopic heller cardiomyotomy without an anti-reflux
      procedure.
AB  - Certain technical features of laparoscopic Heller cardiomyotomy (LHM) remain
      controversial, including the extent of the myotomy and the indication for an
      antireflux procedure. We completed a retrospective chart review of all patients
      who underwent LHM for achalasia at 1 tertiary care institution to review our
      institutional experience with LHM without an antireflux procedure. Forty patients
      underwent a LHM performed by 2 surgeons, 65% of whom had previous medical
      management (Botox: 12 patients, LES dilatation: 14). The operating time was
      significantly increased in patients with Botox injections (98.3 vs. 71.1 minutes,
      P = 0.005). There were 3 intraoperative complications (mucosal injury in 3
      patients, 2 had Botox injections). Postoperative evaluation demonstrated a mean
      dysphagia score of 0.2, a mean heartburn score of 3.2, and a mean LES pressure of
      6.32 mm Hg. Thirty-two patients are maintained on acid-suppressing medications
      with good control of reflux symptoms. LHM without an antireflux procedure
      achieves excellent clinical outcomes in most patients with achalasia regardless
      of previous medical management. Previous medical management may present a greater
      technical challenge and may place patients at increased risk of mucosal injury.

PMID- 15956896
TI  - Value of contrast-enhanced magnetic resonance cholangiography in patients
      undergoing laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) is the preferred treatment for symptomatic
      gallstone disease. Biliary injury during LC is still a serious problem. Knowledge
      of anatomic detail is important for not encountering the injury. Magnetic
      resonance cholangiography (MRC) is a noninvasive method for imaging the biliary
      ducts. However, MRC has many drawbacks such as not showing anatomic structures in
      detail and respiratory motion. In this study, contrast-enhanced MRC was used to
      show cystic ducts that are not seen on MRC. Reasons for patient referral for MRC
      and contrast-enhanced MRC included suspicion of cholecystolithiasis,
      adenomyomatosis, and gallbladder polyp. Our results show that routine MRC
      revealed cystic ducts in 38 patients (77.5%) and contrast-enhanced MRC in 46
      patients (93.8%). Intraoperative cholangiography (IOC) was taken as gold standard
      for all patients. We found that contrast-enhanced MRC can provide a useful
      supplement to MRC in patients with cystic ducts not seen on MRC. To our
      knowledge, this is the first study of visualization of a cystic duct in patients
      undergoing LC depicted by both MRC and contrast-enhanced MRC.

PMID- 15956897
TI  - Laparoscopic splenectomy: a selected retrospective review.
AB  - Previous investigators have suggested that laparoscopic splenectomy should be the
      procedure of choice for the treatment of benign hematologic disorders
      unresponsive to medical therapy. To evaluate the safety and utility of
      laparoscopic splenectomy for a variety of splenic disorders, we reviewed our
      collective experience at 2 institutions. We studied our 8-year experience by
      retrospective chart review. Patient demographic data, splenic pathology,
      intraoperative events, concomitant procedures, and all adverse perioperative
      events were recorded. A total of 131 patients had laparoscopic splenectomy, and
      there were 8 conversions to open surgery. Pathology included 63 with idiopathic
      thrombocytopenic purpura (ITP), 23 malignancies, 12 thrombotic thrombocytopenic
      purpura (TTP), 10 autoimmune hemolytic anemia (AIHA), and 23 others. Accessory
      spleens were noted in 21 patients (16%). Concomitant surgical procedures included
      12 hepatic biopsies, 4 distal pancreatectomies, 4 cholecystectomies, and 7
      others. Mean operative time was 170 minutes. There were 16 major complications in
      16 patients and 2 deaths. Median postoperative length of stay was 3 days.
      Conversions, due mostly to bleeding, are related to splenic pathology and medical
      comorbidity and are not temporally related to surgical experience (learning
      curve). The morbidity, mortality, and conversion rates were low. Laparoscopic
      splenectomy permits an appropriate abdominal exploration and is associated with a
      short hospital stay. It is the procedure of choice for most indications for
      splenectomy.

PMID- 15956898
TI  - Laparoscopic resection of low rectal cancer with a mean follow-up of seven years.
AB  - The role of laparoscopic surgery in the management of cancer of the rectum
      remains controversial. The main concern is the risk of port-site metastasis and
      neoplastic dissemination. The aim of this study was to evaluate prospectively 29
      patients who underwent laparoscopic resection with total mesorectum excision for
      lower rectal carcinoma with a mean follow-up of 7 years. From January 1993 to
      December 1998, 29 patients with proven low (<10 cm from the anal verge) rectal
      cancer were operated by a laparoscopic approach. They were followed up at 1-, 3-,
      and then every 6-month intervals, postoperatively for an average of 7 years. Mean
      operative time was 157 +/- 46 minutes. The conversion rate was 13.7% (4 cases): 1
      for tumor invasion of adjacent structures, 2 for inadequate margins of resection,
      and 1 for locally advanced cancer. First flatus occurred after 37.3 +/- 11.5
      hours, and oral feeding started at 48.3 +/- 23 hours postoperatively. The length
      of the suprapubic incision for extraction of the specimen was 5.6 +/- 1.7 cm.
      Hospital stay was 7.2 +/- 3.0 days. There were no deaths. The morbidity rate was
      14.8%. Length of the specimen, lateral and distal margins, and the number of
      lymph nodes resected were comparable to those of an open surgical approach. The
      average postoperative follow-up was 7 years (5-10 years). The late complication
      rate was 3.7%. There were no port-site metastases. Five-year recurrence rates
      were 0%, 22%, and 37% for Duke's A, B, and C cancers, respectively. The 5-year
      survival rate was 100% for Duke's A, 89% for B, and 50% for C. Laparoscopic
      resection for low rectal cancer with total mesorectum excision can be performed
      with the same oncologic principles, low morbidity, and long-term complications.
      Five-year survival and recurrence rates are comparable to those of open surgery.

PMID- 15956899
TI  - Comparative cost-analysis of a propofol-cisatracurium-based anesthesia with
      remifentanil or fentanyl for laparoscopic surgery.
AB  - To compare the intraoperative costs of intravenous propofol-based anesthesia for
      laparoscopic cholecystectomy, a total of 42 patients were randomly assigned to
      receive remifentanil or fentanyl as adjuvant using the bispectral index
      anesthesia monitoring. The average anesthesia calculated costs per hour (and per
      minute) were 79.45 (1.32) in the fentanyl group and 65.36 (1.09) in the
      remifentanil group. The calculated mean cost per patient was 76.56 in the
      fentanyl group and 58.86 in the remifentanil group. In conclusion, for propofol
      cisatracurium-based anesthesia for laparoscopic surgery, when applying the
      bispectral index to guide the administration of hypnotic anesthetic drugs and
      ensure an adequate and stable depth of anesthesia, the cost of anesthesia is
      lower using remifentanil as an adjuvant rather than fentanyl. The clinical
      relevance is that it could be the intravenous anesthesia technique of choice in
      laparoscopic surgery for cholecystectomy from a cost-minimization standpoint.

PMID- 15956900
TI  - A standardized surgical technique for mastoscopic axillary lymph node dissection.
AB  - To standardize the surgical technique for mastoscopic axillary lymph node
      dissection (MALND). Mastoscopic lymph node dissection was performed consistently
      by a group of surgeons in 316 cases of breast cancer. The mean operation time was
      46.7 minutes with minimal bleeding, and the median number of lymph nodes
      dissected at each operation was 17.0. There were no operative complications in
      any case, nor did trocar implantation or tumor diffusion occurring during the
      mean follow-up time of 15.1 months. MALND is distinctive and practicable in
      operative anatomy as well as safe and convenient. The location of critical
      anatomy such as the intercostobrachial nerve, lateral thoracic artery, medial
      thoracic nerve, and thoracoepigastric vein should be clearly identified to avoid
      damage to them, so that is the great advantage of MALND.

PMID- 15956901
TI  - Transgastric laparoscopic resection of a giant esophageal lipoma.
AB  - We present an unusual case of a giant, pedunculated esophageal lipoma originating
      in the mid-esophagus ball-valving through the gastroesophageal junction resulting
      in intermittent obstruction and hemorrhage. Endoscopic ultrasonography revealed a
      1 cm in diameter vessel in the stalk of the polyp, and endoscopic resection was
      not performed. Transgastric laparoscopic resection with endoscopic guidance was
      successfully performed using 2 balloon-tipped laparoscopic trocars inserted
      laparoscopically into the gastric lumen through separate gastrotomies.
      Intraoperative esophagoscopy confirmed proper port placement and the exact
      location of the mass. Under direct visualization, a Snowden-Pencer grasper was
      used to pull the polyp down into the stomach and an Endo-GIA blue articulating
      stapler was used to transect its stalk. The polyp was retrieved via an endopouch
      placed through the intragastric laparoscopic port. We conclude that transgastric
      laparoscopy should be considered for the resection of a variety of pedunculated
      esophageal lesions when the use of standard endoscopic techniques is not
      possible.

PMID- 15956902
TI  - Laparoscopic transgastric resection of a gastric lipoma presenting as acute
      gastrointestinal hemorrhage.
AB  - A 71-year-old man was admitted to the emergency unit with upper gastrointestinal
      bleeding, due to a gastric lipoma, which was controlled with conservative
      measures. Endoscopy and computed tomography revealed a 4-cm submucosal mass
      located in the posterior wall of gastric antrum. The patient underwent an
      elective laparoscopic transgastric resection of the lipoma and discharged on
      postoperative day 6. Gastric lipomas are uncommon tumors that can be incidentally
      found. They produce symptoms similar to peptic ulcer disease and can lead to
      obstruction. Gastric lipomas, which may lead to life-threatening complications
      such as bleeding, can be safely and reliably treated by laparoscopic transgastric
      resection.

PMID- 15956903
TI  - Laparoscopic wedge resection for gastric ectopic pancreas.
AB  - Ectopic pancreas is pancreatic tissue found outside the usual anatomic location
      of the pancreas. It is often an incidental finding in clinical practice and can
      be found at different sites in the gastrointestinal tract. Although usually a
      silent anomaly, it may become clinically evident when complicated by pathologic
      changes such as inflammation, bleeding, obstruction, and malignant
      transformation. We describe a case of ectopic pancreas located in the stomach,
      treated with a laparoscopic approach that permitted isolation and complete
      resection of the lesion. The patient was discharged without complications and
      without recurrence of symptoms.

PMID- 15956904
TI  - Simultaneous laparoscopic treatment for diseases of the gallbladder, stomach, and
      colon.
AB  - We describe a successful simultaneous laparoscopic treatment of a gallstone and
      gastric and colonic neoplasms. The patient was a 72-year-old man with epigastric
      discomfort. Abdominal ultrasound revealed a gallstone 2 cm in diameter.
      Gastroscopy revealed a 3-cm protruding submucosal tumor in the gastric fundus and
      colonoscopy revealed a 2-cm sessile lesion in the sigmoid colon. He underwent
      simultaneous laparoscopic treatment of the 3 organs because of the high risk of
      perforation or bleeding after gastric or colonic resection. This required the use
      of 5 ports, and a 3.5-cm incision was made in the left lower quadrant to access
      the 3 organs. The laparoscopic procedures consisted of cholecystectomy, partial
      stapled resection of the gastric fundus, and partial resection of the sigmoid
      colon. The histopathologic diagnoses were chronic cholecystitis, leiomyoma of the
      stomach, and tubulovillous adenoma with severe dysplasia of the colon. The
      operation took 183 minutes and blood loss was minimal. The patient started oral
      intake from the second postoperative day and was discharged uneventfully. He had
      from no postoperative complications or abdominal symptoms during a 15-month
      follow-up period. To our knowledge, this is a first successful clinical report of
      simultaneous laparoscopic treatment of 3 organ disorders.

PMID- 15956905
TI  - Successful laparoscopic repair of spontaneous rectosigmoid rupture with an acute
      transanal small bowel evisceration.
AB  - This report describes the first successful laparoscopic approach for transanal
      small bowel evisceration secondary to spontaneous rectal rupture, indeed a very
      rare event. A brief description of our technique and the pathophysiologic
      features of this condition are given.

PMID- 15956906
TI  - Prevention and management of access port site hernia associated with the
      laparoscopic adjustable gastric band.
AB  - Access port site hernia is a rare complication associated with the laparoscopic
      adjustable gastric band (LAGB). Specifically, this unique problem occurs when a
      fascial defect allows herniation adjacent to the Silastic tubing connects the
      LAGB to the access port. A 48-year-old woman who had previously undergone
      placement of LAGB presented with a bulge lateral to the access port; physical
      examination revealed a hernia near the access port. At laparoscopy, a large
      portion of omentum was herniated lateral to the Silastic tubing at the port site.
      This was laparoscopically repaired by first reducing the omentum and then placing
      a surgical mesh underlay to cover the defect; the patient recovered uneventfully.
      Access port site hernia is a rare complication with only a single case report
      published in the literature. We present a case of access port site hernia that
      was laparoscopically repaired. In addition, we have identified several important
      technical aspects that may contribute to the development of access port site
      hernias.

PMID- 15956907
TI  - Internal hernia through the mesenteric opening after laparoscopy-assisted
      transverse colectomy.
AB  - We report a case of a rare complication in laparoscopic colectomy. A 55-year-old
      woman underwent a laparoscopy-assisted transverse colectomy for transverse colon
      cancer. On the 5th postoperative day, she developed bowel obstruction.
      Decompression by a long intestinal tube failed to resolve the bowel obstruction.
      She underwent operative intervention. Abdominal exploration showed jejunal loop
      caused by a strangulation forming on an internal hernia through the mesenteric
      opening at the anastomotic colonic stumps, which had not been sutured during the
      previous operation. Our experience might indicate the need for closure of small
      mesenteric opening after laparoscopic colectomy.

PMID- 15956908
TI  - Hemihepatic ischemia for laparoscopic liver resection.
AB  - Laparoscopic hepatectomy has been recently proposed for the treatment of liver
      tumors. However, because of technical difficulties such as control of hemorrhage
      from the transection plane and large intrahepatic veins, laparoscopic hepatectomy
      has not been widely developed. The technique of hemihepatic ischemia has been
      used by the authors in conventional liver resection over the past 10 years with
      reduced splanchnic congestion and excellent hemostatic control. To minimize both
      intraoperative bleeding and circulatory and biochemical disturbances due to the
      interruption of blood flow to the liver, the authors describe a new technique
      combining hemihepatic ischemia and laparoscopic liver resection.

PMID- 15956909
TI  - Re: Appendix retrieval after laparoscopic appendectomy: a safe and inexpensive
      technique. Surg Lap Endosc Percut Tech. 2003;13(5):322-324.

PMID- 15956916
TI  - What's new in carotid artery stenting.

PMID- 15956917
TI  - Endovascular treatment strategies for supra-aortic arterial occlusive disease.
AB  - Because of the focal nature of stenoses or occlusions in the supra-aortic
      vasculature, the high blood-pressures in this area and the very low morbidity
      rates related to percutaneous therapy have largely replaced surgical
      revascularization as the initial treatment of choice for patients with supra
      aortic arterial occlusive disease. The initial technical success and durability
      of percutaneous angioplasty (PTA) and stenting in these lesions is excellent.
      Nevertheless several factors can make PTA and stenting a complex procedure that
      requires advanced endovascular skills for a successful outcome. Profound
      knowledge of surgical reconstruction techniques or extra-anatomic bypasses
      remains mandatory, as it is occasionally required for failure of endovascular
      techniques or if contraindications exist.

PMID- 15956918
TI  - Techniques for carotid artery stenting under cerebral protection.
AB  - Carotid angioplasty and stenting is an alternative to carotid endarterectomy in
      the treatment of carotid artery stenosis. During the stenting process, however,
      distal embolization usually occurs, and the particles released may cause
      neurologic problems or death. Thus, the safety of carotid stenting depends partly
      on use of a cerebral protection device during the procedure. Three principal
      types of protection mechanisms have been developed: distal balloon occlusion,
      distal filtration, and proximal occlusion with or without reversal of flow.
      Products using these mechanisms have been manufactured by a variety of companies,
      and many are used routinely outside the United States (US). One distal filter,
      the RX Accunet, has been approved by the US Food and Drug Administration for
      clinical use. Large clinical trials of most of the newest carotid stents and
      cerebral protection devices are under way, and some initial results have been
      reported. Several clinical series in which cerebral protection was employed have
      also been described. Each type of protection device has advantages and
      disadvantages, which are discussed in this review.

PMID- 15956919
TI  - PRIAMUS--proximal flow blockage cerebral protectIon during carotid stenting:
      results from a multicenter Italian registry.
AB  - AIM: The aim of this Italian prospective registry was to evaluate the
      applicability and efficacy of the Mo.Ma Device (Invatec, Roncadelle, Italy) for
      the prevention of cerebral embolization during carotid artery stenting (CAS) in a
      real world population. METHODS: In 4 Italian centers, 416 patients (300 men; mean
      age 71.6+/-9 years) between October 2001 and March 2005 were enrolled in a
      prospective registry. Two-hundred and sixty-four symptomatic (63.46%) with >50%
      diameter stenosis and 152 (36.54%) asymptomatic patients with >70% diameter
      stenosis were included. The Mo.Ma Proximal Flow Blockage Embolic Protection
      System was used to perform protected CAS, achieving cerebral protection by
      endovascular clamping of the common carotid artery (CCA) and of the external
      carotid artery (ECA). RESULTS: Technical success, defined as the ability to
      establish protection with the Mo.Ma device and to deploy the stent, was achieved
      in 412 cases (99.03%). The mean duration of flow blockage was 4.91+/-1.1 min.
      Transient intolerances to flow blockage were observed in 24 patients (5.76%), but
      in all cases the procedure was successfully completed. No peri-procedural strokes
      and deaths were observed. Complications during hospitalization included 16 minor
      strokes (3.84%), 3 transient ischemic attacks (0.72%), 2 deaths (0.48%) and 1
      major stroke (0.24%). This resulted in a cumulative rate at discharge of 4.56%
      all strokes and deaths, and of 0.72% major strokes and deaths. All the patients
      underwent thirty-day follow-up. At thirty-day follow-up, there were no deaths and
      no minor and major strokes, confirming the overall cumulative 4.56% incidence of
      all strokes and deaths rate, and of 0.72% rate of major strokes and deaths at
      follow up. In 245 cases (58.89%) there was macroscopic evidence of debris after
      filtration of the aspirated blood. CONCLUSIONS: This Italian multicenter registry
      confirms and further supports the efficacy and applicability of the endovascular
      clamping concept with proximal flow blockage in a broad patient series. Results
      match favorably with current available studies on carotid stenting with cerebral
      protection.

PMID- 15956920
TI  - Advantages and indications of transcervical carotid artery stenting with carotid
      flow reversal.
AB  - AIM: The aim of this Italian prospective registry was to evaluate the
      applicability and efficacy of the Mo.Ma Device (Invatec, Roncadelle, Italy) for
      the prevention of cerebral embolization during carotid artery stenting (CAS) in a
      real world population. METHODS: In 4 Italian centers, 416 patients (300 men; mean
      age 71.6+/-9 years) between October 2001 and March 2005 were enrolled in a
      prospective registry. Two-hundred and sixty-four symptomatic (63.46%) with >50%
      diameter stenosis and 152 (36.54%) asymptomatic patients with >70% diameter
      stenosis were included. The Mo.Ma Proximal Flow Blockage Embolic Protection
      System was used to perform protected CAS, achieving cerebral protection by
      endovascular clamping of the common carotid artery (CCA) and of the external
      carotid artery (ECA). RESULTS: Technical success, defined as the ability to
      establish protection with the Mo.Ma device and to deploy the stent, was achieved
      in 412 cases (99.03%). The mean duration of flow blockage was 4.91+/-1.1 min.
      Transient intolerances to flow blockage were observed in 24 patients (5.76%), but
      in all cases the procedure was successfully completed. No peri-procedural strokes
      and deaths were observed. Complications during hospitalization included 16 minor
      strokes (3.84%), 3 transient ischemic attacks (0.72%), 2 deaths (0.48%) and 1
      major stroke (0.24%). This resulted in a cumulative rate at discharge of 4.56%
      all strokes and deaths, and of 0.72% major strokes and deaths. All the patients
      underwent thirty-day follow-up. At thirty-day follow-up, there were no deaths and
      no minor and major strokes, confirming the overall cumulative 4.56% incidence of
      all strokes and deaths rate, and of 0.72% rate of major strokes and deaths at
      follow up. In 245 cases (58.89%) there was macroscopic evidence of debris after
      filtration of the aspirated blood. CONCLUSIONS: This Italian multicenter registry
      confirms and further supports the efficacy and applicability of the endovascular
      clamping concept with proximal flow blockage in a broad patient series. Results
      match favorably with current available studies on carotid stenting with cerebral
      protection.

PMID- 15956921
TI  - Does carotid artery stenting work on the long run: 5-year results in high-volume
      centers (ELOCAS Registry).
AB  - AIM: Although the first long-term results of Carotid Artery Stenting (CAS) became
      available only recently, CAS has become an accepted treatment for carotid artery
      disease. We report CAS data up to 5 years, both late stroke rate and patency
      rates as observed in 4 high-volume European centers. METHODS: Between February 1,
      1993 and December 31, 2004, 2 172 patients were selected over the 4 participating
      centres, with intention to treat endovascularly. Conscientious follow-up was done
      according to the in-hospital stipulations of each centre and was entered into a
      database both retrospectively and prospectively. Long-term restenosis and stroke
      death rates were investigated and statistically analysed and stratified using the
      Kaplan-Meier method. RESULTS: Of the 2 172 patients with intention to treat 2 165
      (99.7%) were technically successful. Of these 306 (14.1%) were performed without
      and 1 859 (85.9%) with embolic protection device (EPD); 96 patients (4.4%)
      received balloon dilation only and stenting was performed in 2 069 (95.6%) cases.
      Kaplan-Meier analysis of major stroke/all death and of significant restenosis
      (>50%) for the total population showed stroke/death rates of 4.1% (nar=1 356),
      10.1% (nar=476) and 15.5% (nar=138); and restenosis rates of 1% (nar=1 363), 2%
      (nar=480) and 3.4% (nar=139), after 1, 3 and 5 years respectively. CONCLUSIONS:
      The patency and stroke/death rates resulting from our database analysis are
      pleasing and indicate that CAS also on longer term is a valuable treatment method
      for carotid artery disease. Due to the fact that our dataset contains prospective
      as well as retrospective data, it may have its limitations. Until this moment,
      data indicating that certain patient subgroups are at increased risk for
      neurological complications and in-stent restenosis during and after CAS are
      sparse. Further multivariant analysis on this unique dataset is mandatory in
      order to identify any potential links in between plaque morphology, preprocedural
      neurological complications, risk factor distribution, procedural steps and
      clinical outcome.

PMID- 15956922
TI  - Drug coated stents for carotid intervention.
AB  - Carotid endarterectomy has demonstrated its superiority over medical treatment of
      symptomatic as well as asymptomatic stenosis of the extracranial carotid artery.
      Although minimally invasive methods initially failed to produce similar results,
      stent implantation is becoming an alternative technique for stroke prophylaxis
      with technical advances, cerebral protection and careful patient selection. Even
      though restenosis does not seem to be a major limitation compared to coronary
      interventions, in-stent restenosis might occur more frequently with an increasing
      number of procedures performed and longer follow-up periods. Drug eluting stents
      have shown to attenuate this complication. Currently, no clinical data on drug
      eluting stents in carotid arteries are available. This article discusses the
      current literature on carotid artery stenting and the potential role of drug
      eluting stents in this field.

PMID- 15956923
TI  - Complications of carotid artery stenting.
AB  - AIM: The aim of this study was to deal with complications that can be managed by
      vascular surgery. METHODS: From March 2000 through May 2004, 171 patients (112
      male, 59 female, mean age 66.2 years) underwent carotid artery stenting (CAS). Of
      these 171 interventions, 154 were CAS with percutaneous trasluminal angioplasty
      (PTA), 5 CAS without PTA, and 12 patients had only a PTA. RESULTS: In 171
      patients who received CAS, 5 suffered a stroke within 7 days and 3 a transient
      ischemic attack. Twenty-one percent of the patients developed an in-stent
      restenosis >50% within 6 months following the intervention. Twenty-two patients
      with a recurrent in-stent restenosis were treated by re-PTA. Eight patients of
      this group of 22 re-PTAs developed a recurrent in-stent restenosis. They were
      converted with patch angioplasty or PTFE interposition. These 8 conversions were
      performed without morbidity or mortality. CONCLUSIONS: The preferable operative
      technique in patients with recurrent in-stent restenosis is open conventional
      operation with stent removal and patch angioplasty or graft interposition. The
      procedure can be performed at a low risk. In our series, we had no morbidity and
      mortality, and no cranial nerve lesion.

PMID- 15956924
TI  - Carotid endarterectomy in heart transplant patients.
AB  - AIM: The aim of this study was to determine the clinical outcome of carotid
      endarterectomy in heart transplant recipients and morphologic features of
      atherosclerotic plaques removed during operation. METHODS: Between April 1993 and
      October 2001 5 heart transplant patients with symptomatic carotid stenosis >70%
      underwent carotid endarterectomy with regional anesthesia, including a staged
      bilateral procedure in one patient. Cholesterol, triglycerides, HDL-cholesterol,
      LDL-cholesterol were evaluated in each patient. The plaques ( n=6) underwent
      histologic analysis after carotid endarterectomy. Carotid artery duplex imaging
      was added to the routine postoperative evaluation. RESULTS: Carotid plaques
      resulted to be echolucent on B-mode ultrasound examination. Cholesterol,
      triglycerides and LDL-cholesterol levels were found to be increased, while HDL
      cholesterol were decreased. All patients underwent successful carotid
      endarterectomy; there were no perioperative deaths, major neurologic or cardiac
      events. The mean length of stay was 2.2 days. The mean follow-up was 44 months.
      In 1 case, an asymptomatic restenosis >50% occurred 9 months later and, in 2
      other cases, a contralateral mild stenosis was found 12 and 36 months later. One
      patient had a progressive contralateral stenosis, requiring operation 18 months
      later. High lipid content and heterogeneous cellular infiltration were observed,
      including macrophages, T-lymphocytes, neutrophils, and also eosinophils in the
      rapidly progressing plaque. CONCLUSIONS: Heart transplant patients receiving
      immunosuppression may successfully undergo carotid endarterectomy, without
      increased risk, but progression of atherosclerotic disease in the carotid
      arteries seems to continue, despite lipid-lowering regimen and antiplatelet
      therapy.

PMID- 15956925
TI  - The expression of platelet-derived growth factor and connective tissue growth
      factor in different types of abdominal aortic aneurysms.
AB  - AIM: An atherosclerotic abdominal aortic aneurysms (AAAA) differ from
      inflammatory abdominal aortic aneurysms (IAAA), which are characterized by a non
      specific inflammatory reaction leading to considerable aneurysmal wall thickness
      from the media to adventitia and retroperitoneal fibrosis in the surrounding
      tissue. Platelet-derived growth factor (PDGF) and its receptor have been
      localized to specific cell types within atherosclerotic plaques. Human connective
      tissue growth factor (CTGF) is a cysteine rich polypeptide that has similar
      structures to PDGF and has been implicated in connective tissue formation. PDGF
      and CTGF may play a role in the development of aneurysmal walls in both AAAA and
      IAAA. METHODS: Using in situ hybridization technique with DIG-labeled RNA probes
      and immunostaining, we investigated CTGF gene expression, and expression of PDGF
      and its receptor protein, in human aneurysmal walls. RESULTS: Expression of CTGF
      mRNA was found on vascular smooth muscle cells (VSMC) in specimens from AAAA and
      IAAA. Strong CTGF expression was localized in VSMC around calcification in AAAA.
      In IAAA, strong expression of CTGF was observed around inflammatory cells. In the
      aneurysmal walls of AAAA, PDGF A and B chains were strongly stained on small
      vessels, and the PDGF beta receptor was also strongly stained on VSMC around
      calcification. In the aneurysmal wall of IAAA, weak expressions of PDGF A and B
      chains were observed in endothelial cells of vessel walls around the inflammatory
      cells, but the intensity of expression was much weaker than that on the vessel
      walls in AAAA. CONCLUSIONS: Such differences in fibrogenic cytokine expression
      may be involved in characteristic aneurysmal formation.

PMID- 15956926
TI  - Baseline oxygen delivery is associated with an increased risk of severe
      postoperative complications after elective open repair of abdominal aortic
      aneurysm.
AB  - AIM: Oxyhemodynamic parameters have been shown to have a relevant impact on the
      immediate postoperative outcome after major surgery, but it is not known their
      specific impact on the outcome after elective repair of abdominal aortic aneurysm
      (AAA). METHODS: One-hundred and forty-one patients underwent elective open repair
      of infrarenal AAA and hemodynamic parameters were monitored perioperatively.
      RESULTS: One patient (0.7%) died postoperatively, 23 (16.3%) experienced a
      myocardial ischemic event and 9 of them (6.4%) had a myocardial infarction.
      Baseline oxygen delivery was not predictive of such myocardial ischemic events.
      Thirty-three patients (23.4%) suffered severe postoperative complications. The
      median baseline oxygen delivery was 429.5 mL/min/m2 among patients who had severe
      postoperative complications, whereas it was 505.5 mL/min/m2 among those who did
      not have severe complications (p=0.03). However, this parameter did not retain
      its significance at multivariate analysis. When only the preoperative variables
      were included in the logistic regression model, the Glasgow Aneurysm Score
      (P=0.004, Oddsratio 1.94, 95% C.I. 1.24-3.05) was the only predictor of severe
      postoperative complications. The Glasgow Aneurysm Score was significantly
      correlated with baseline oxygen delivery (P=-0.256, P=0.003). CONCLUSIONS:
      Baseline oxygen delivery is associated with an increased risk of severe
      postoperative complications after elective open repair of AAA. The value of
      preoperative optimization of oxygen delivery should be evaluated in this patient
      population.

PMID- 15956927
TI  - Does adenosine pharmacologically precondition human myocardium during coronary
      bypass surgery?
AB  - AIM: Adenosine (Ado) triggers ischemic preconditioning. We investigated whether
      Ado provides additional myocardial protection in patients during intermittent
      aortic cross-clamping (IAC) bypass surgery. METHODS: The placebo group was made
      of 15 male of 66+/-8 years while the Ado group was made of 19 male of 65+/-10
      years. The patients of the Ado group had a 3-vessel heart disease and were
      treated with elective surgery. With the aortic cross-clamping, Ado or vehicle
      were infused over 10 min at systemic pressure together with sufficient blood via
      the aortic root. Blood samples before anaesthesia and onset of ECC, 1 hour after
      end of surgery, and on day 1 and 2 post-surgery to assess CK-MB and troponin I
      were performed. Hemodynamic measures (heart rate, left ventricular pressure,
      max/min pressure rise, central venous pressure) before installation and 15 min
      after completion of the coronary artery bypass. Different ECGs for
      electrophysiological analyses were performed. RESULTS: Hemodynamic and laboratory
      measures revealed no significant advantages of either protocol. Mortality rate
      was zero in both groups. CONCLUSIONS: The comparable outcome is likely due to
      cardioprotection provided by both IAC bypass surgery and hypothermia, which might
      obscure beneficial effects of pharmacological preconditioning in patients with
      good left ventricular function (ejection fraction >50%). As the benefit might
      have been marginal, it may well become apparent in a larger study on patients
      with more severe left ventricular dysfunction.

PMID- 15956928
TI  - Effects of adenosine and defibrotide adjunct to a standard crystalloid
      cardioplegic solution.
AB  - AIM: Adenosine has many actions potentially useful as adjunct to a cardioplegia.
      Defibrotide was recently shown to have protective effects during cardiac arrest.
      The aim of this study was to compare these 2 substances to delineate their
      profile of action in the setting of cardioplegic arrest. METHODS: A Langendorff
      model for isolated rat hearts was employed: 3 groups of 8 hearts each were used,
      respectively with plain St. Thomas cardioplegia as control (group C), and the
      same solution added with adenosine (group A) or defibrotide (group D). The hearts
      had a baseline perfusion for 30 minutes with Krebs-Henseleit solution at 37
      degrees C, cardioplegia administration for 3 minutes, then 30 minutes of ischemia
      without any perfusion and finally 30 minutes of reperfusion with Krebs-Henseleit
      solution at 37 degrees C. RESULTS: The time to attain heart arrest was 20%
      shorter in group A, but this difference did not reach statistical significance
      (A: 13.6+/-1.5; D: 16.8+/-2.7; C: 17.3+/-2.2 s). The heart rate during
      reperfusion in group A was almost identical to baseline, while in both group C
      and D it was significantly lower (A: 101%, D: 93.4%, C: 82.4%, p<0.01).A and D
      decreased significantly the release of creatine phospokinase compared to group C
      (p=0.006). Lactate dehydrogenase release was lower in both treatment groups,
      although statistical significance was not reached. Peak positive dP/dT decreased
      more in controls during reperfusion (A: -23+/-6%, D: -17+/-5%, C: -31+/-5%,
      p=ns). Negative dP/dT was significantly worse in controls compared to both
      treatments (A: -19+/-6%, D: -12+/-5%, C: -34+/-7%, p=0.035). CONCLUSIONS: Both
      adenosine and defibrotide have protective effects in an isolated model of
      cardioplegic arrest. Adenosine is significantly more active on heart rate while
      defibrotide is more active on contractily. Further studies are justified in order
      to test the combination of these 2 drugs.

PMID- 15956929
TI  - Creatine phosphate administration preserves myocardial function in a model of off
      pump coronary revascularization.
AB  - AIM: Off pump coronary artery bypass grafting (OPCAB) involves, and is
      occasionally impaired by obligatory regional myocardial ischemia, particularly
      with the use of proximal coronary in-flow occlusion techniques. Intracoronary
      shunts do not guarantee absence of distal ischemia given their small inner
      diameter and the presence of proximal coronary stenosis. Additional adjunctive
      measures to provide short-term myocardial protection may facilitate OPCAB. High
      energy phosphate supplementation with creatine phosphate prior to ischemia may
      attenuate ischemic dysfunction. METHODS: In a rodent model of a transient
      coronary occlusion and myocardial ischemia, 36 animals underwent preischemic
      intravenous infusion of either creatine phosphate or saline, 10 minutes of
      proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion.
      Rats underwent continuous intracavitary pressure monitoring and cellular ATP
      levels were quantified using a luciferin/luciferase bioluminescence assay.
      RESULTS: Within 2 minutes of ischemia onset, creatine phosphate animals exhibited
      statistically significant greater preservation of myocardial function compared to
      controls, an augmentation which persisted throughout the duration of ischemia and
      subsequent reperfusion. Furthermore, significantly greater cellular ATP levels
      were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue,
      n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014).
      CONCLUSIONS: A strategy of intravenous high-energy phosphate administration
      successfully prevented ischemic ventricular dysfunction in a rodent model of
      OPCAB.

PMID- 15956930
TI  - Myocardial protection in diabetics with left main stem disease: which is the best
      strategy?
AB  - AIM: Diabetes mellitus is a well known risk factor for extensive coronary
      disease. The optimal route for cardioplegia administration in patients with
      severe ischaemic heart disease undergone surgery, especially with left main stem
      disease (LMSD) is still under debate. Aim of the study is to compare 2 different
      strategies of myocardial protection in diabetics with LMSD. METHODS: Between
      January 2000 and June 2003 90 consecutive patients with type II diabetes mellitus
      and LMSD undergoing isolated myocardial revascularization were divided into 2
      groups according to the route of cardioplegia delivery: antegrade in 45 patients
      (group A), antegrade followed by intermittent retrograde in 45 (group B). ECG,
      Troponin I, MB-CPK, MB-CPK mass were performed at 12, 24, 48, and 72 hours
      postoperatively. Echocardiography was performed preoperatively and before
      hospital discharge. RESULTS: Groups were homogeneous in preoperative and
      intraoperative variables, apart from higher incidence of unstable angina and
      longer cardiopulmonary bypass time in Group B and hypertension in Group A.
      Hospital deaths, in intensive care units (ITU) stay, perioperative acute
      myocardial infarction, intra-aortic balloon pump support, postoperative recovery
      of left ventricle ejection fraction and wall motion score index were similar in
      both groups. In hospital stay proved shorter in group B (p=0.002), whereas
      postoperative atrial fibrillation was higher in group A (p<0.001), as
      postoperative inotropic support (p=0.006). Troponin I proved significantly higher
      in group A from the 12 degrees to the 72 degrees postoperative hour (p<0.0001).
      CONCLUSIONS: Despite major in hospital end-points did not differ with strategy of
      cardioplegia administration, combined route of intermittent blood cardioplegia
      allows better biochemical and perioperative results in diabetics with LMSD.

PMID- 15956931
TI  - G-CSF producing giant tumor in the lung.

PMID- 15956932
TI  - Inflammatory pseudotumor of the lung mimicking pleural fibrous mesothelioma.

PMID- 15956933
TI  - Predicted postoperative FEV1 in patients undergoing surgery for lung cancer: is
      it still useful?

PMID- 15956934
TI  - The role of somatostatin receptor scintigraphy (Octreoscan) during follow-up of
      patients after bronchial carcinoid resection. A prospective study.

PMID- 15956935
TI  - Subcutaneous hydatidosis due to iatrogenic spreading of cystic fluid during
      surgery.

PMID- 15956936
TI  - Pediatric ophthalmology and Strabismus in Brazil.

PMID- 15956938
TI  - The effect on pediatric ophthalmologists of the randomized trial of patching
      regimens for treatment of moderate amblyopia.
AB  - PURPOSE: To investigate the implementation of the recommendations of the
      randomized trial of patching regimens for treatment of moderate amblyopia in
      children. METHODS: A questionnaire was e-mailed to 380 members of the American
      Association for Pediatric Ophthalmology and Strabismus. RESULTS: Ninety responses
      were received. The majority of questionnaire respondents did not alter their
      clinical practice of patching subsequent to publication of the results of the
      patching trial. Thirty-nine percent made no modification whatsoever; an
      additional 33% made rare adjustments, and only 12% claimed to have adapted the
      amount of patching hours to the recommendations of the study. CONCLUSIONS: It is
      evident from the questionnaire results that the majority of pediatric
      ophthalmologists that replied to the questionnaire did not alter their clinical
      practice of patching subsequent to publication of the results of the patching
      trial.

PMID- 15956939
TI  - The effect of media press coverage on parental preferences in amblyopia
      treatment.
AB  - BACKGROUND: Amblyopia has traditionally been treated by full-time occlusion of
      the sound eye. Recent studies have looked at the efficacy of atropine
      penalization and less patching in the treatment of amblyopia. These studies have
      drawn much attention from the lay press. This media attention may influence
      parent treatment preferences. METHODS: We distributed two news releases recently
      published by national newspapers to parents presenting to an outpatient pediatric
      eye clinic. They were then asked to rank atropine drops, 2-hour, 6-hour, and full
      time patching (FTP) in order of preference. We then supplied additional
      information published in the scientific studies, but not mentioned in the lay
      press, and parents were asked to rerank their preferences. RESULTS: A total of 53
      surveys were completed. The frequency with which each method (atropine, 2-hour, 6
      hour, FTP) was initially ranked #1 was 66, 21, 2, and 11%, respectively. The
      frequency each was ranked #1 in the follow-up survey was 30, 26, 8, and 38%,
      respectively. The Wilcoxon matched-pair signed-ranks test demonstrated
      significant changes in treatment preferences (atropine, z = -4.204, P < 0.0001; 2
      hour patch, z = -2.574, P = 0.0101; 6-hour patch, z = 4.484, P < 0.0001; FTP, z =
      3.703, P = 0.0002). CONCLUSION: After having read press releases regarding
      amblyopia treatment, parents' preferences favored atropine and less patching.
      After being given additional information about the results of these studies,
      there was a strong shift in opinions in favor of more patching and away from
      atropine. The media appear to play an important role in influencing parent
      treatment preferences.

PMID- 15956940
TI  - The effects of L-dopa on the functional magnetic resonance imaging response of
      patients with amblyopia: a pilot study.
AB  - PURPOSE: We investigated the effects of a single dose of levodopa (L-dopa) on the
      level and extent of visual cortex activation of subjects with amblyopia and
      normal subjects using blood oxygenation level-dependent functional magnetic
      resonance imaging (fMRI). SUBJECTS AND METHODS: Six patients with amblyopia and 9
      control patients were recruited. A baseline fMRI session was followed by a second
      session 90 minutes after the dose of L-dopa. Visual stimuli included vertical
      sinusoidal gratings with spatial frequencies of 1 and 2 cpd that were
      counterphased at 4 Hz. Stimuli were presented monocularly and binocularly. The
      fMRI response was characterized by the total volume and the average level of
      activation within the occipital cortex. An interocular absolute difference (IDIF)
      was defined in terms of said measures for between-population analysis of
      monocular data. RESULTS: After the administration of L-dopa, visual acuity
      improved significantly ( P = 0.026) from 0.72 +/- 0.21 (mean +/- SD) to 0.64 +/-
      0.24 LogMAR in the amblyopic eye, although remaining the same in the dominant eye
      and in the eyes of control subjects. The response to L-dopa was found to be
      population-specific, as indicated by a significant treatment-by-population
      interaction for the volume of activation IDIF ( P = 0.018) measure: subjects with
      amblyopia exhibited a post-treatment increase in the volume of activation IDIF
      whereas control subjects showed a less prominent decrease. This post-treatment
      increase of IDIF in subjects with amblyopia may be explained by the decrease in
      the volume of activation found for the amblyopic eye after L-dopa ( P = 0.038).
      No L-dopa-related activation changes were detected for dominant eye or binocular
      stimulation in the amblyopic group, and no change was detected in control
      subjects. CONCLUSION: L-dopa elicits a population-specific modulation of the fMRI
      response, namely, a reduced total volume of activation from the amblyopic eye
      despite improvement in visual acuity.

PMID- 15956941
TI  - Correction of large amblyopiogenic refractive errors in children using the
      excimer laser.
AB  - PURPOSE: We sought to determine whether laser subepithelial keratomileusis
      (LASEK) and photorefractive keratectomy (PRK) are effective methods for
      correcting amblyopiogenic refractive errors in children. METHODS: Thirty-six eyes
      in 35 amblyopic children, who ranged in age from 4 to 16 years (mean, 8.4 years),
      received treatment for large magnitude ametropia. Seventy-two percent (25/35) of
      the children had a neurobehavioral disorder and/or were noncompliant with
      spectacle or contact lens wear. Myopia ranged from -3.25 to -24.25 D (mean, 
      11.48 D); one patient had hyperopia of +5.87 D. Correction was tailored to match
      the refractive error of the nonamblyopic eye. VISX Star S2/S3 excimer lasers were
      used in manual or auto-tracking modes, and corneal centration was achieved using
      brief, general anesthesia. Mean follow-up was 29.2 months (range, 4-42 months).
      RESULTS: Myopia correction averaged -8.95 +/- 2.89 D (range, -3.25 to -15.50).
      Eighty-nine percent (31 children) were corrected to within +/- 1.00 D of goal
      refraction and the remaining 11% to within 2.0 D of the goal (most were
      undercorrected). Acuity improved postoperatively in 97%; by 1 optotype line in
      37% and by 2 or more in 60%. No child lost acuity. Binocularity improved in 69%
      (24/35) and remained the same in 31%. Corneal haze measured grade 0-1 in 78%,
      grade 2 in 14%, and grade 3-4 in 8%. Myopic regression exceeding congruent with
      1.0 D/year (0.08 D/month) occurred in 50% (18/36) of eyes treated. No substantial
      differences were observed in PRK- (n = 18) versus LASEK- (n = 17) treated
      children. CONCLUSIONS: Laser refractive surgery is effective for correcting
      anisometropic myopia in amblyopic children. Recurrence of myopia is common.
      Further study is indicated to determine long-term stability and safety of the
      procedure in this population.

PMID- 15956942
TI  - Comparison of modified anchored "hang-back technique (HBT)" with conventional HBT
      in bimedial rectus recession.
AB  - PURPOSE: We conducted a retrospective study to establish whether bimedial rectus
      recession (BMR) using a modified "hang-back technique" (HBT) is comparable with
      conventional HBT. METHODS: Consecutive patients younger than the age of 16
      underwent BMR during 1999 and 2000 with at least a 6-month postoperative follow
      up period were included. In 1999, all patients had operations performed with
      conventional HBT, whereas those in 2000 were conducted with modified HBT. Angles
      of strabismus were measured preoperatively and at 2 weeks, 2 months, and 6 months
      postoperatively. RESULTS: Thirty-nine and 43 patients underwent BMR using
      conventional and modified HBT respectively. Preoperative angles for near and
      distance were 43.6 (PD) versus 43.5 PD and 36.4 PD versus 36.8 PD. At 6 months'
      postop, the mean angles for near and distance were 6.4 PD Eso (range, 35 PD Eso -
      40 PD Exo) and 5.4 PD Eso (range, 35 PD Eso - 35 PD Exo) in the conventional
      group: 8.1 PD Eso (range, 35 PD Eso - 20 PD Exo) and 6.3 PD Eso (range, 35 PD Eso
      - 25 PD Exo) in the modified group. The overall success rate (alignment to within
      10 PD of orthotropia for distance and near) was similar between the two groups
      (conventional HBT:69.2% vs. modified HBT: 67.4%, P = 0.352). However, modified
      HBT was found to be associated with significantly lower consecutive exotropia
      rate postoperatively at 6 months (4.7% vs. 20.5%, P = 0.031). CONCLUSION: BMR
      using modified HBT is as effective as conventional HBT but with a significantly
      lower consecutive exotropia rate.

PMID- 15956943
TI  - Anterior chamber intraocular lens (ACIOL) placement after pars plana lensectomy
      in pediatric Marfan syndrome.
AB  - INTRODUCTION: The management of subluxed crystalline lenses in patients with
      Marfan syndrome is challenging and may require lensectomy. Options for
      postoperative optical correction include aphakic spectacles, aphakic contact
      lens, posterior chamber IOLs sutured to the ciliary sulcus, and open-loop
      flexible anterior chamber IOLs (ACIOL). We recently began placing ACIOLs in all
      patients with Marfan Syndrome who were younger than 18 years of age and required
      lensectomy. METHODS: We used a retrospective chart review design for this study.
      RESULTS: Eight eyes of 5 patients were treated with pars plana vitrectomy, pars
      plana lensectomy, and primary ACIOL placement. Follow-up ranged from 9 to 16
      months, with a mean of 12.7 months. Ages ranged from 5 to 17 years with a mean of
      9 years. Three eyes were functionally aphakic at the time of surgery. Of the 5
      eyes with a portion of the lens remaining in the visual axis, none maintained
      accommodative function by near visual acuity testing. Best-corrected distance
      visual acuity preoperatively ranged from 20/50 to 20/400, with an average of
      20/80 (0.65 logMAR). Postoperative acuity ranged from 20/20 to 20/50, with an
      average acuity of 20/32 (0.20 logMAR). One patient had an iatrogenic sector
      iridectomy. No patients experienced corneal decompensation, increased intraocular
      pressure, persistent inflammation, IOL displacement, or explantation during the
      follow-up period. CONCLUSIONS: Although long-term follow-up data are unavailable,
      our cases of primary ACIOL placement in children with Marfan syndrome indicate
      that this therapy should be considered.

PMID- 15956944
TI  - Isolated superior oblique tucking: an effective procedure for superior oblique
      palsy with profound superior oblique underaction.
AB  - PURPOSE: To compare efficacy and complications of isolated unilateral superior
      oblique tucking in patients with unilateral superior oblique palsy (SOP). METHOD:
      A retrospective analysis of 24 cases of unilateral SOP, 13 Acquired (group 1),
      and 11 Congenital (group 2), who underwent isolated unilateral superior oblique
      tuck over a 13-year period was performed. RESULTS: The mean preoperative vertical
      deviation in primary gaze was 10 +/- 3 PD for group 1 and 12 +/- 5 PD for group 2
      and mean vertical deviation in lateral gaze of affected superior oblique was 19
      +/- 5 PD for group 1 and 21 +/- 9 PD for group 2. The mean postoperative vertical
      deviation in primary gaze for group 1 after a mean follow-up period of 15 +/- 21
      months was 1 +/- 3 PD; for group 2 after a mean follow-up period of 17 +/- 13
      months was 2 +/- 3 PD, and in lateral gaze of affected superior oblique was 3 +/-
      5 PD for group 1 and 5 +/- 6 PD for group 2. The mean correction of vertical
      deviation in primary gaze at last follow-up was 8 +/- 2 PD for group 1 and 9 +/-
      5PD for group 2 ( P > 0.05) and in the lateral gaze field of affected superior
      oblique muscle was 16 +/- 4 PD for group 1 and 15 +/- 5 PD for group 2 ( P >
      0.05). The mean preoperative torsion was 9 +/- 4 degrees for group 1 and 9 +/- 2
      degrees for group 2; mean postoperative torsion was 1.2 +/- 2.2 degrees for group
      1 and 1 +/- 1 degrees for group 2. The mean torsion corrected for group 1 was 8
      +/- 3 degrees and for group 2 was 8 +/- 2 degrees ( P > 0.05). Only one patient
      in group 1 and three patients in group 2 required reoperation to correct residual
      deviation. A mild postoperative limitation to elevation in adduction was seen in
      all cases but was asymptomatic and lessened over time. CONCLUSION: Isolated
      unilateral superior oblique tucking corrected a large amount of the vertical
      deviation and torsion with minimal complications in selective patients of both
      congenital and acquired superior oblique palsy. Superior oblique tucking is a
      safe and effective procedure and can be considered in patients with SOP meeting
      selective criteria.

PMID- 15956945
TI  - Cataract extraction and primary hydrophobic acrylic intraocular lens implantation
      in infants.
AB  - PURPOSE: We sought to report the incidence of visual axis opacification and to
      evaluate the complication and reoperation rates after intraocular lens
      implantation in infants. METHODS: Twenty-one infants (31 eyes) who had cataract
      extraction with primary hydrophobic acrylic IOL implantation between October 1996
      and May 2002 were reviewed. Posterior capsule was left intact in 14 eyes (group
      A); posterior capsulorrhexis or capsulotomy with anterior vitrectomy was
      performed in 17 eyes (group B). Complication and reoperation rates were compared
      with an age-matched control group of 17 patients (33 eyes) who were left aphakic
      after pars plicata lensectomy. Mean follow-up period was 41 months (range, 22-75
      months) in group A, 37 months (range, 10-75 months) in group B, and 52 months
      (range, 7-97 months) in the control group. RESULTS: Mean age of the patients was
      6.8 months (range, 3-10 months) in group A, 8.9 months (range, 3-18 months) in
      group B, and 4.9 months (range, 1-15 months) in the control group. Visual axis
      opacification was significantly higher in group A (86%) when compared with group
      B (17.6%; P < 0.0001). No significant difference was found in terms of pupillary
      irregularities and peripheral anterior synechiae formation between pseudophakic
      and aphakic group ( P = 0.43 and P = 0.306, respectively), whereas pigment
      dispersion and fibrinous reaction were significantly more common in the
      pseudophakic group ( P = 0.002). Serious complications, such as retinal
      detachment, pseudophakic bullous keratopathy, and secondary glaucoma, did not
      develop in any eye. Reoperation rate was significantly higher in group A (78%)
      when compared with group B (17%) and the control group (12%; P = 0.0011 and P <
      0.0001, respectively). CONCLUSIONS: Visual axis opacification requiring a
      reoperation was significantly more common in patients with an intact posterior
      capsule. To decrease the reoperation rate and maintain a clear visual axis,
      posterior capsulorrhexis with anterior vitrectomy should be performed. Even
      although early complications were quite frequent, serious late complications were
      not encountered in any eye. Therefore, under appropriate conditions, IOL
      implantation is a suitable alternative in infants.

PMID- 15956946
TI  - A retrospective review of 287 consecutive children in singapore presenting with
      intermittent exotropia.
AB  - BACKGROUND: Intermittent exotropia, X(T), is a relatively common form of
      strabismus among children in Singapore. The purpose of this study is to see how
      children presenting with this condition fared during a period of 5 years.
      METHODS: The medical records of all children younger than 16 years who presented
      to the eye clinic at the Singapore National Eye Centre with X(T) between January
      1992 and December 1995 were reviewed retrospectively. RESULTS: A total of 287
      patients satisfied the entry requirements of this study. Estimated age of onset
      of exotropia was documented in 161 subjects. The mean age of estimated onset was
      3.0 +/- 2.5 years. The mean age of presentation was 6.1 +/- 3.1 years. The mean
      amount of distant exotropia was 36.4 +/- 12.5 prism diopters (PD). Seventy-two
      percent of children had poor/no distant control. During a 3-year period, the size
      of exotropia appears to remain constant (within 5 PD of original) in 48% and
      improved >5 PD in 32%. Control of distant exotropia remained the same in 63%,
      improved in 17% and worsened in 20%. Near exotropia was initially present in only
      35.5%. The mean amount of near exotropia, when present, was 25.9 +/- 13.7PD. Near
      control remained the same in 65% and worsened in 22%. More variation was observed
      in subjects presenting before 5 years of age. One hundred sixty-two (56.4%)
      subjects underwent surgery. The mean age of surgery was 8.0 +/- 2.6 years.
      Surgery resulted in a final strabismus size between 10 PD exotropia and 5PD
      esotropia in 65.2% at 1 year postoperation. CONCLUSION: Half the subjects
      presenting with an intermittent exotropia eventually had surgery. In the
      remaining nonsurgical subjects, intermittent exotropia, once present, appeared to
      be a relatively stable condition.

PMID- 15956947
TI  - Iris hypoplasia and aorticopulmonary septal defect: a neurocristopathy.
AB  - BACKGROUND: Errors in neural crest development are responsible for a number of
      ocular disorders. In some cases, these ocular abnormalities may be associated
      with systemic disorders, some of which may be life threatening. METHODS: We
      reviewed the medical record of 3 children from 2 institutions with a similar
      constellation of ocular and cardiac abnormalities. RESULTS: All 3 children had
      iris hypoplasia with pupils 6-7 mm in diameter that had minimal or no response to
      light or pharmacological agents. The ocular examinations were otherwise normal.
      All 3 children also had large aorticopulmonary septal defects which were
      surgically repaired. CONCLUSIONS: We report an association between iris
      hypoplasia and aorticopulmonary septal defects. Like the iris stroma, the
      aorticopulmonary septum forms from neural crest cells during embryogenesis which
      divide the truncus arteriosus into the ascending aorta and pulmonary trunk.
      Children with iris hypoplasia should undergo an immediate cardiac evaluation. It
      is important that opthalmologists be aware of the association between these two
      disorders since an aorticopulmonary septal defect is a life-threatening disorder.

PMID- 15956948
TI  - Psychosocial aspects of mothers of children with strabismus.
AB  - PURPOSE: The aim of the study was to investigate the psychological profile of
      mothers of children with strabismus, their attitudes to their children, and their
      family functioning. METHODS: This study was conducted at Dokuz Eylul University
      School of Medicine, from 2000 to 2002 and involved a series of 30 children with
      strabismus and 31 healthy controls. All mothers were asked to complete Beck
      Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Parental
      Attitude Research Instrument (PARI), and Family Assessment Device (FAD). RESULTS:
      Mothers of the children with strabismus had significantly higher depression
      scores ( P = 0.042) compared with mothers of the control group. They demonstrated
      significantly lower scores in democratic attitude, meaning that they failed to
      constitute a supportive and friendship relation with their children, ( P =
      0.0001). These mothers had significantly higher scores in rejection of maternal
      role ( P = 0.017) as compared with mothers of the control group. They were
      nervous, distressed, and angry in the relationship with their children, with
      unhappiness and more dissatisfaction with respect to maternal role. Mothers of
      the children with strabismus had poor role functioning in the family, which is
      related to satisfying the food, clothing, and support needs ( P = 0.034). They
      also had poor affective responsiveness, which means the ability of family members
      to respond with appropriate emotion ( P = 0.003), and poor general functioning (
      P = 0.040) as compared with mothers of the control group. CONCLUSIONS: This study
      demonstrated that, for mothers who have children with strabismus, strabismus had
      an adverse effect on their lives, and their family relationships.

PMID- 15956949
TI  - Visual field defects in deformational posterior plagiocephaly.
AB  - PURPOSE: We sought to determine whether visual field abnormalities occur in
      infants with deformational posterior plagiocephaly and to assess whether there is
      a relationship between the severity and laterality of visual field abnormalities
      with the severity and laterality of skull deformity. METHODS: A retrospective
      chart review was performed on 40 consecutive infants with deformational posterior
      plagiocephaly. Each was tested with standardized binocular arc perimetry in the
      horizontal plane. Sixteen patients also had 3-dimensional computed tomography of
      the skull. Hemifield asymmetry of >/=20 degrees and/or a decrease in hemifield
      values by >/=20 degrees from established normal patients was considered abnormal.
      Visual field data from study patients was plotted against previously published
      normative data. Graphs comparing visual field defects and laterality to cranial
      asymmetry also were generated. RESULTS: Thirty-five percent of infants with
      deformational posterior plagiocephaly had constriction of one or both hemifields
      by at least 20 degrees from established normal patients. Hemifield asymmetry of
      20 degrees or more was found in 17.5% of infants tested. There was a significant
      difference in the worse hemifield values measured in each patient and the
      standard visual fields obtained from normative data ( P = 0.036). There was no
      correlation between the laterality of the visual fields to the laterality of the
      defects. A correlation between severity of hemifield constriction and % asymmetry
      on computed tomography was noted ( P = 0.209). CONCLUSIONS: Deformational
      posterior plagiocephaly may affect visual field development but neither the
      laterality nor the severity of skull deformity is predictive of the severity of
      visual field defects.

PMID- 15956950
TI  - Strabismus surgery under augmented topical anesthesia.
AB  - PURPOSE: Recently, topical lidocaine 2% jelly had been used in
      phacoemulsification and trabeculectomy surgeries. The purpose of this study is to
      evaluate the efficacy and stability of one-stage adjustable suture using topical
      lidocaine jelly 2% in combination with intravenous nalbuphine (Nubain). METHODS:
      Forty adult patients aged 16 to 46 years (median, 24 years) underwent adjustable
      rectus muscle surgery under topical lidocaine jelly 2% and intravenous 10 mg
      nalbuphine given 10 minutes before surgery. Adjustment was performed on the
      operating table before conjunctival closure. The stability of adjustment was
      studied by comparing the postadjustment deviation to that at 1 day, 1 week, and 3
      weeks postoperatively. Success was defined as alignment within 10 prism diopters
      on distant fixation. Analgesia was assessed using Verbal Description Scale.
      Changes in vital signs were recorded during surgery to evaluate the oculocardiac
      reflex. RESULTS: Forty rectus muscles were recessed, 22 muscles were resected, 3
      muscles were tucked, and 2 muscles were retrieved. During the operation, 35
      patients expressed no pain, 3 patients complained of discomfort, and 2 patients
      complained of distressing pain and required an additional 10 mg of intravenous
      nalbuphine. Thirty-eight patients (95%) were successfully aligned during the
      first postoperative day, 37 patients (92.5%) after 1 week, and 36 patients (90%)
      after 3 weeks. Intraoperative cardiac monitoring did not record positive
      oculocardiac reflex in any patient. CONCLUSION: Lidocaine jelly in combination
      with intravenous nalbuphine is an effective topical anesthesia strategy that
      provides for the patient's comfort and the surgeon's ability to fine-tune ocular
      alignment on the operating table.

PMID- 15956951
TI  - Isolated herpes simplex keratoconjunctivitis in a neonate born by cesarean
      delivery.
AB  - Herpes simplex virus (HSV) infection can be devastating in the neonate. The
      disease most commonly presents as 1 of 3 clinical manifestations: disseminated
      visceral infection (with and without central nervous system involvement),
      isolated meningoencephalitis, and infection limited to the skin, eyes, and/or
      mucous membranes (SEM). Exposure leading to neonatal infection typically occurs
      as peripartum vertical transmission, most typically by direct contact with
      urogenital lesions or infected genital secretions, or as an ascending infection
      exploiting disrupted chorioamniotic membranes. We present a novel case of a
      newborn girl who developed HSV-2 keratoconjunctivitis despite being delivered via
      an elective, uncomplicated, repeat cesarean over intact chorioamniotic membranes
      in the absence of active clinical maternal HSV infection and despite having a
      negative medical history of previous orolabial or genital herpetic infection.

PMID- 15956952
TI  - Pseudomonas aeruginosa endophthalmitis in a preterm infant.
AB  - Bacterial endophthalmitis is rare in the neonatal period. It occurs in
      susceptible individuals such as preterm infants. Pseudomonas aeruginosa, a Gram
      negative bacillus, has been identified as the causative organism in more than 75%
      of invasive neonatal eye infections. The source may be endogenous; secondary to
      septicemia or exogenous, including reports of nosocomial infections and those
      infections arising from the birth canal. We report the case of a preterm infant
      who developed pseudomonas endophthalmitis, septicemia, and meningitis after a
      corneal abrasion.

PMID- 15956953
TI  - Congenital retinal dystrophy and corneal opacity in trisomy 8 mosaicism.
AB  - Trisomy 8 mosaicism can present with a wide variety of systemic and
      ophthalmologic manifestations. We report a patient with an extinguished
      electroretinogram and diffuse retinal pigment epithelial abnormalities suggestive
      of a rod-cone dystrophy, which has not been previously reported in association
      with trisomy 8. A finding that has been described in several patients with
      trisomy 8 is a central corneal opacity, but there are no data regarding the
      natural history of this finding; the corneal opacity in our patient spontaneously
      improved. This case expands the clinical spectrum of this rare entity.

PMID- 15956954
TI  - Spontaneous carotid cavernous fistula in a pediatric patient: case report and
      review of literature.
AB  - A 14-year-old boy presented with spontaneous, painless proptosis of the right
      eye. Computed tomography and digital subtraction angiography revealed an indirect
      carotid cavernous fistula. Because there were no sight-threatening complications,
      we adopted a conservative approach. The condition resolved 1 month after initial
      presentation, with angiographically confirmed spontaneous obliteration of the
      fistula.

PMID- 15956955
TI  - Unilateral poliosis of the eyelashes in children associated with vitiligo.
AB  - Two children developed sudden progressive unilateral poliosis of their eyelashes
      during the course of a 1-month period. The poliosis occurred in the absence of
      any associated condition apart from vitiligo, both of which have remained
      isolated findings after 2 and 4 years of follow-up, respectively. Although it is
      important to exclude associated conditions, poliosis of the eyelashes may be a
      benign condition that may remain unilateral.

PMID- 15956957
TI  - Spectacle prescriptions for preschool children.

PMID- 15956959
TI  - Restoration of binocular single vision after long-term fusion disruption.

PMID- 15956960
TI  - Brain tumors in children: evaluation and management.
AB  - Brain and spinal cord tumors represent the most common solid tumors in children.
      Recent advances in imaging techniques, neurosurgical techniques, chemotherapy
      approaches, and radiation oncology have resulted in some improvement in overall
      survival and morbidity. However, the prognosis for many children with high-grade
      and malignant brain tumors remains guarded in terms of mortality and long-term
      sequelae. Given the rarity of tumors in children, patients are likely best served
      at tertiary center that can offer a comprehensive multidiscipline approach.

PMID- 15956962
TI  - Role of insulin-like growth factor 1 receptor signalling in cancer.
AB  - The insulin-like growth factor (IGF-1) signalling is highly implicated in cancer.
      In this signalling the IGF-1 receptor (IGF-1R) is unquestionable, the
      predominating single factor. IGF-1R is crucial for tumour transformation and
      survival of malignant cell, but is only partially involved in normal cell growth.
      This is in part due to the interactions with oncogenes. Recent findings suggest a
      close interplay with the p53/MDM2 pathway. Disturbances in components in the
      p53/MDM2/IGF-1R network may cause IGF-1R upregulation and growth advantage for
      the cancer cell. Targeting of IGF-1R is more and more seen as a promising option
      for future cancer therapy. Single chain antibodies and small molecules with
      selective effects on IGF-1R dependent malignant growth are of particular
      interest. Forthcoming clinical trials are welcome and will indeed be the only way
      to evaluate the impact of IGF-1R targeting in human cancer.

PMID- 15956963
TI  - Mammographic density and the risk of breast cancer in Japanese women.
AB  - Using an automated method for detecting mammographic mass, the authors evaluated
      the relation between quantitatively measured density and the risk of breast
      cancer in a case-control study among Japanese women. The case subjects were 146
      women newly diagnosed and histologically confirmed with breast cancer at a
      general hospital. A total of 659 control women were selected from those who
      attended a breast cancer mass screening at this hospital. Significantly increased
      odds ratios (ORs) of breast cancer were observed for breast densities of 25-49
      and 50-74%, but not for densities of 75-100% as compared with 0% in premenopausal
      women after controlling for covariates (ORs = 4.0, 4.3, and 1.4, respectively).
      In postmenopausal women, ORs were significantly increased for breast densities of
      25-50% (OR = 3.0) and 50-100% (OR = 4.2). Total breast area was significantly
      associated with the risk of breast cancer independent of density percent or dense
      area in postmenopausal women. These data suggested that mammographic density was
      associated with the risk of breast cancer in Japanese women as is the case in
      Caucasian women. However, the associations of the risk of breast cancer with
      breast size and a high breast density greater than 75%, needs to be confirmed in
      future studies.

PMID- 15956965
TI  - Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre
      clinical evidence.
AB  - Activation of the endothelin A receptor (ET(A)) by endothelin-1 (ET-1) mediates
      events that regulate mitogenesis, apoptosis, angiogenesis and metastasis in
      tumours. Specific blockade of ET(A) may have anticancer effects, while retaining
      beneficial endothelin B receptor (ET(B))-mediated effects such as apoptosis and
      clearance of ET-1. ZD4054 is an orally active, specific ET(A) antagonist in
      clinical development. In receptor-binding studies, ZD4054 specifically bound to
      ET(A) with high affinity; no binding was detected at ET(B). In a randomised
      placebo-controlled trial in eight healthy volunteers, a single oral dose of
      ZD4054 reduced forearm vasoconstriction in response to brachial artery infusion
      of ET-1, thus providing clinical evidence of ET(A) blockade. ET(B) blockade was
      assessed in an ascending, single-dose, placebo-controlled trial in 28 volunteers.
      For all doses of ZD4054, mean plasma ET-1 concentrations measured at 4 and 24 h
      were within the placebo reference range (a rise in ET-1 would indicate ET(B)
      blockade) and there was no evidence of dose-related changes. These data confirm
      the specificity of ZD4054 for ET(A), with no activity at ET(B) in a clinical or
      preclinical setting. As a result of this specificity, ZD4054 has the potential to
      block multiple ET(A)-induced pathological processes, while allowing beneficial
      ET(B)-mediated processes to continue, which may, in turn, lead to an effective
      cancer therapy.

PMID- 15956964
TI  - p53 status and response to radiotherapy in rectal cancer: a prospective
      multilevel analysis.
AB  - The aim of this study was to evaluate, in a prospective study, the predictive
      role of p53 status analysed at four different levels in identifying the response
      to preoperative radiotherapy in rectal adenocarcinoma. Before treatment, 70
      patients were staged and endoscopic forceps biopsies from the tumour area were
      taken. p53 status was assessed by total cDNA sequencing, allelic loss analysis,
      immunohistochemistry, and p53 antibodies. Neoadjuvant treatment was based on
      preoperative radiotherapy or radiochemotherapy. Response to therapy was evaluated
      after surgery by both pathologic downstaging and histologic tumour regression
      grade. In all, 35 patients (50.0%) had p53 gene mutations; 44.4% of patients had
      an allelic loss; nuclear p53 overexpression was observed in 39 patients (55.7%);
      and p53 antibodies were detected in 11 patients (16.7%). In the multilevel
      analysis of p53 status, gene mutations correlated with both nuclear protein
      overexpression (P < 0.0001) and loss of heterozygosity (P = 0.013). In all, 29
      patients (41.4%) were downstaged by pathologic analysis, and 19 patients (29.2%)
      were classified as tumour regression grade 1. Whatever the method of evaluation
      of treatment response, no correlation between p53 alterations and response to
      radiotherapy was observed. Our results do not support the use of p53 alterations
      alone as a predictive marker for response to radiotherapy in rectal carcinoma.

PMID- 15956966
TI  - Decreased expression of haemoglobin beta (HBB) gene in anaplastic thyroid cancer
      and recovery of its expression inhibits cell growth.
AB  - Anaplastic thyroid cancer (ATC) is one of the most fulminant and foetal diseases
      in human malignancies. However, the genetic alterations and carcinogenic
      mechanisms of ATC are still unclear. Recently, we investigated the gene
      expression profile of 11 anaplastic thyroid cancer cell lines (ACL) and
      significant decreased expression of haemoglobin beta (HBB) gene in ACL.
      Haemoglobin beta is located at 11p15.5, where loss of heterozygosity (LOH) was
      reported in various kinds of cancers, including ATC, and it has been suggested
      that novel tumour suppressor genes might exist in this region. In order to
      clarify the meaning of decreased expression of HBB in ATC, the expression status
      of HBB was investigated with ACL, ATC, papillary thyroid cancer (PTC) and normal
      human tissues. Haemoglobin beta showed significant decreased expression in ACLs
      and ATCs; however, in PTC, HBB expressed equal to the normal thyroid gland. In
      addition, HBB expressed in normal human tissues ubiquitously. To validate the
      tumour-suppressor function of HBB, cell growth assay was performed. Forced
      expression of HBB in KTA2 cell, which is a kind of ACL, significantly suppressed
      KTA2 growth. The mechanism of downregulation of HBB in ATC is still unclear;
      however, our results suggested the possibility of HBB as a novel tumour
      suppressor gene.

PMID- 15956967
TI  - Gene expression signatures for colorectal cancer microsatellite status and HNPCC.
AB  - The majority of microsatellite instable (MSI) colorectal cancers are sporadic,
      but a subset belongs to the syndrome hereditary non-polyposis colorectal cancer
      (HNPCC). Microsatellite instability is caused by dysfunction of the mismatch
      repair (MMR) system that leads to a mutator phenotype, and MSI is correlated to
      prognosis and response to chemotherapy. Gene expression signatures as predictive
      markers are being developed for many cancers, and the identification of a
      signature for MMR deficiency would be of interest both clinically and
      biologically. To address this issue, we profiled the gene expression of 101 stage
      II and III colorectal cancers (34 MSI, 67 microsatellite stable (MSS)) using high
      density oligonucleotide microarrays. From these data, we constructed a nine-gene
      signature capable of separating the mismatch repair proficient and deficient
      tumours. Subsequently, we demonstrated the robustness of the signature by
      transferring it to a real-time RT-PCR platform. Using this platform, the
      signature was validated on an independent test set consisting of 47 tumours (10
      MSI, 37 MSS), of which 45 were correctly classified. In a second step, we
      constructed a signature capable of separating MMR-deficient tumours into sporadic
      MSI and HNPCC cases, and validated this by a mathematical cross-validation
      approach. The demonstration that this two-step classification approach can
      identify MSI as well as HNPCC cases merits further gene expression studies to
      identify prognostic signatures.

PMID- 15956968
TI  - Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL
      mutations in renal cell carcinoma.
AB  - Epidermal growth factor receptor (EGFR) and tumour growth factor alpha (TGFalpha)
      are frequently overexpressed in renal cell carcinoma (RCC) yet responses to
      single-agent EGFR inhibitors are uncommon. Although von Hippel-Lindau (VHL)
      mutations are predominant, RCC also develops in individuals with tuberous
      sclerosis (TSC). Tuberous sclerosis mutations activate mammalian target of
      rapamycin (mTOR) and biochemically resemble VHL alterations. We found that RCC
      cell lines expressed EGFR mRNA in the near-absence of other ErbB family members.
      Combined EGFR and mTOR inhibition synergistically impaired growth in a VHL
      dependent manner. Iressa blocked ERK1/2 phosphorylation specifically in wt-VHL
      cells, whereas rapamycin inhibited phospho-RPS6 and 4E-BP1 irrespective of VHL.
      In contrast, phospho-AKT was resistant to these agents and MYC translation
      initiation (polysome binding) was similarly unaffected unless AKT was inhibited.
      Primary RCCs vs cell lines contained similar amounts of phospho-ERK1/2, much
      higher levels of ErbB-3, less phospho-AKT, and no evidence of phospho-RPS6,
      suggesting that mTOR activity was reduced. A subset of tumours and cell lines
      expressed elevated eIF4E in the absence of upstream activation. Despite similar
      amounts of EGFR mRNA, cell lines (vs tumours) overexpressed EGFR protein. In the
      paired cell lines, PRC3 and WT8, EGFR protein was elevated post-transcriptionally
      in the VHL mutant and EGF-stimulated phosphorylation was prolonged. We propose
      that combined EGFR and mTOR inhibitors may be useful in the subset of RCCs with
      wt-VHL. However, apparent differences between primary tumours and cell lines
      require further investigation.

PMID- 15956971
TI  - Phase II study of gemcitabine plus oxaliplatin as first-line chemotherapy for
      advanced non-small-cell lung cancer.
AB  - This phase II study evaluated the response rate and tolerability of gemcitabine
      oxaliplatin chemotherapy in non-small-cell lung cancer (NSCLC) patients.
      Chemonaive patients with stage IIIB or IV NSCLC received gemcitabine 1000 mg m(
      2) on days 1 and 8, followed by oxaliplatin 130 mg m(-2) on day 1. Cycles were
      repeated every 21 days for up to six cycles. From February 2002 to May 2004, 60
      patients were enrolled into the study in seven Italian institutions. We observed
      one complete response (1.7%) and 14 partial responses (23.3%), for an overall
      response rate of 25.0% (95% confidence interval, 14.7-37.9%). The median duration
      of response was 5.9 months (range 1.5-17.1 months). With a median follow-up of
      6.7 months, median time to progressive disease and overall survival were 2.7
      (range 1.9-3.4 months) and 7.3 months (range 7.2-8.6 months), respectively. The
      main grade 3-4 haematological toxicities were transient neutropenia in 11.7% and
      thrombocytopenia in 8.3% of the patients. Nausea/vomiting was the main grade 3-4
      nonhaematological toxicity, occurring in 10.0% of the patients. Two (3.3%)
      patients developed grade 3 neurotoxicity. Our results show that gemcitabine
      oxaliplatin chemotherapy is active and well tolerated in patients with advanced
      NSCLC, deserving further study, especially for patients not eligible to receive
      cisplatin.

PMID- 15956972
TI  - High-level expression of Rad51 is an independent prognostic marker of survival in
      non-small-cell lung cancer patients.
AB  - High-level expression of Rad51, a key factor in homologous recombination, has
      been observed in a variety of human malignancies. This study was aimed to
      evaluate Rad51 expression to serve as prognostic marker in non-small-cell lung
      cancer (NSCLC). A total of 383 non-small-cell lung tumours were analysed
      immunohistochemically on NSCLC tissue microarrays. High-level Rad51 expression
      was observed in 29.4% (100 out of 340) of cases. Patients whose tumours displayed
      high-level Rad51 expression showed a significantly shorter median survival time
      of 19 vs 68 months (P<0.0001, log-rank test). Similarly T status, N status, M
      status, clinical stage and histological tumour grade were significant prognostic
      markers in univariate Cox survival analysis. Importantly, Rad51 expression
      (P<0.0001) together with tumour differentiation (P<0.009), clinical stage
      (P=0.004) and N status (P=0.0001) proved to be independent prognostic parameters
      in multivariate analysis. Rad51 expression predicted the outcome of squamous cell
      cancer as well as adenocarcinoma of the lung. Our results suggest that Rad51
      expression provides additional prognostic information for surgically treated
      NSCLC patients. We hypothesise that the decreased survival of NSCLC patients with
      high-level expression of Rad51 is related to an enhanced propensity of tumour
      cells for survival, antiapoptosis and chemo-/radioresistance.

PMID- 15956973
TI  - Accumulation of mitochondrial DNA mutation with colorectal carcinogenesis in
      ulcerative colitis.
AB  - We recently reported that oxidative stress elicited by chronic inflammation
      increases the mutation of mitochondrial DNA (mtDNA) and possibly correlates with
      precancerous status. Since severe oxidative stress is elicited in the colorectal
      mucosa of individuals with ulcerative colitis (UC), the possible occurrence of an
      mtDNA mutation in the inflammatory colorectal mucosa and colitic cancer was
      investigated. Colorectal mucosal specimens were obtained from individuals with UC
      with and without colitic cancer and from control subjects. The frequency of mtDNA
      mutations was higher in colorectal mucosal specimens from patients with UC than
      that from control subjects. The levels of 8-hydroxy-2'-deoxyguanosine, a DNA
      adduct by reactive oxygen species, were significantly higher in UC than in
      control. Specimens from patients with colitic cancer contained a significantly
      higher number of mtDNA mutations. The present observations suggest that the
      injury followed by the regeneration of colorectal mucosal cells associated with
      chronic inflammation causes accumulation of mtDNA mutations. The increased
      instability of genes, including those on the mtDNA, is consistent with the high
      and multicentric incidence of colorectal cancer in individuals with UC. Thus,
      analysis of mtDNA could provide a new criterion for the therapeutic evaluation,
      and may be useful for the prediction of risk of carcinogenesis.

PMID- 15956975
TI  - Establishment of an immortalised human ovarian surface epithelial cell line
      without chromosomal instability.
AB  - Epithelial ovarian carcinoma is thought to derive from ovarian surface epithelium
      (OSE). The black box of the early molecular changes in ovarian carcinogenesis is
      being interpreted by the development of experimental systems employing
      immortalised human OSE cells. However, the existing cell lines of the OSE cells
      have limited utility due to chromosomal instability. Our goal was to establish
      new immortalised human OSE cells that retain the original characteristics of the
      primary cells without chromosomal alterations. Using primary human OSE cells
      obtained from a postmenopausal patient with endometrial cancer, five cell lines
      ('HOSE1' lines) were newly established by infection with retroviral expression
      vectors containing type 16 human papillomavirus (HPV-16) E6, E7, a variant E6
      (E6delta151), and Bmi1 polycomb gene, in combination with telomerase reverse
      transcriptase (hTERT). Consequently, five HOSE1s cell lines, HOSE1s-E6/hTERT, 
      E7/hTERT, -E6/E7/hTERT, -E6delta151/E7/hTERT, and -E6delta151/Bmi1/hTERT, grew
      beyond the population doubling number of 200. These cell lines, except for HOSE1
      E6/hTERT, essentially showed the original features of the primary human OSE
      cells. Of them, HOSE1-E7/hTERT preserved diploidy in a kariotype analysis, and
      did not show transformed phenotypes in anchorage-independent growth and tumour
      formation. Thus, HOSE1-E7/hTERT may provide a novel model system with which to
      investigate the mechanisms of early molecular changes.

PMID- 15956974
TI  - Overexpression of neuropilin-1 promotes constitutive MAPK signalling and
      chemoresistance in pancreatic cancer cells.
AB  - Neuropilin-1 (NRP-1) is a novel co-receptor for vascular endothelial growth
      factor (VEGF). Neuropilin-1 is expressed in pancreatic cancer, but not in
      nonmalignant pancreatic tissue. We hypothesised that NRP-1 expression by
      pancreatic cancer cells contributes to the malignant phenotype. To determine the
      role of NRP-1 in pancreatic cancer, NRP-1 was stably transfected into the human
      pancreatic cancer cell line FG. Signal transduction was assessed by Western blot
      analysis. Susceptibility to anoikis (detachment induced apoptosis) was evaluated
      by colony formation after growth in suspension. Chemosensitivity to gemcitabine
      or 5-fluorouracil (5-FU) was assessed by MTT assay in pancreatic cancer cells
      following NRP-1 overexpression or siRNA-induced downregulation of NRP-1.
      Differential expression of apoptosis-related genes was determined by gene array
      and further evaluated by Western blot analysis. Neuropilin-1 overexpression
      increased constitutive mitogen activated protein kinase (MAPK) signalling,
      possibly via an autocrine loop. Neuropilin-1 overexpression in FG cells enhanced
      anoikis resistance and increased survival of cells by > 30% after exposure to
      clinically relevant levels of gemcitabine and 5-FU. In contrast, downregulation
      of NRP-1 expression in Panc-1 cells markedly increased chemosensitivity, inducing
      > 50% more cell death at clinically relevant concentrations of gemcitabine.
      Neuropilin-1 overexpression also increased expression of the antiapoptotic
      regulator, MCL-1. Neuropilin-1 overexpression in pancreatic cancer cell lines is
      associated with (a) increased constitutive MAPK signalling, (b) inhibition of
      anoikis, and (c) chemoresistance. Targeting NRP-1 in pancreatic cancer cells may
      downregulate survival signalling pathways and increase sensitivity to
      chemotherapy.

PMID- 15956976
TI  - Pharmacokinetically guided phase I trial of topotecan and etoposide phosphate in
      recurrent ovarian cancer.
AB  - A pharmacokinetically guided phase I study of topotecan and etoposide phosphate
      was conducted in recurrent ovarian cancer. The scheduling of the topoisomerase I
      and II inhibitors was determined using in vitro activity data. All patients had
      recurrent disease following prior platinum-containing chemotherapy. Patients had
      a World Health Organisation performance status of 0-2 and adequate bone marrow,
      renal and hepatic function. Treatment was with topotecan intravenously for 5 days
      followed immediately by a 5-day intravenous infusion of etoposide phosphate (EP),
      with pharmacokinetically guided dose adjustment. Plasma etoposide levels were
      measured on days 2 and 4 of the infusion. A total of 21 patients entered the
      study. In all, 48% were platinum resistant and 71% had received prior paclitaxel.
      The main toxicities were haematological, short lived and reversible. A total of
      29% of patients experienced grade 4 thrombocytopenia and 66% grade 4 neutropenia
      after the first cycle. Neutropenia and thrombocytopenia was dose limiting. The
      maximum-tolerated dose was topotecan 0.85 mg m(-2) day(-1) days 1-5 followed
      immediately by a 5-day infusion of EP at a plasma concentration of 1 mug ml(-1).
      The response rate (RR) was 28% in 18 evaluable patients. There was marked
      interpatient variability in topoisomerase IIalpha levels measured from peripheral
      lymphocytes, with no observed increase following topotecan. This regimen of
      topotecan followed by EP demonstrated good activity in recurrent ovarian cancer
      and was noncrossresistant with paclitaxel. Both the toxicity and RR was higher
      than would be expected from the single agent data, in keeping with synergy of
      action.

PMID- 15956977
TI  - Role of netrin-1 and netrin-1 dependence receptors in colorectal cancers.
AB  - Although cancer is a multifaceted disease, all cancer types share identical
      molecular and cellular mechanisms. These mechanisms involve a collection of
      alterations critical to the normal physiological functioning of cells, such as
      alterations of growth factor signalling pathways, angiogenesis, cell adhesion
      signals, DNA replication and apoptotic cell death. Many genes involved in the
      processes enumerated above are functionally inactive in tumour cells, designating
      them as putative 'tumour suppressor genes'. Back in the early 1990s, Vogelstein
      and colleagues suggested that a gene called DCC (for Deleted in Colorectal
      Cancer) could be a tumour suppressor gene because it was found to be deleted in
      more than 70% of colorectal cancers, as well as in many other cancers. During the
      last 15 years, controversial data have failed to firmly establish whether DCC is
      indeed a tumour suppressor gene. However, the recent observations that DCC
      triggers cell death and is a receptor for netrin-1, a molecule recently
      implicated in colorectal tumorigenesis, have prompted a renewal of interest in
      the role of DCC in tumorigenesis and suggest that the netrin-1/receptor pairs act
      as novel negative regulators of tumour development.

PMID- 15956978
TI  - Understanding alternative splicing: towards a cellular code.
AB  - In violation of the 'one gene, one polypeptide' rule, alternative splicing allows
      individual genes to produce multiple protein isoforms - thereby playing a central
      part in generating complex proteomes. Alternative splicing also has a largely
      hidden function in quantitative gene control, by targeting RNAs for nonsense
      mediated decay. Traditional gene-by-gene investigations of alternative splicing
      mechanisms are now being complemented by global approaches. These promise to
      reveal details of the nature and operation of cellular codes that are constituted
      by combinations of regulatory elements in pre-mRNA substrates and by cellular
      complements of splicing regulators, which together determine regulated splicing
      pathways.

PMID- 15956979
TI  - The catalytic diversity of RNAs.
AB  - The natural RNA enzymes catalyse phosphate-group transfer and peptide-bond
      formation. Initially, metal ions were proposed to supply the chemical versatility
      that nucleotides lack. In the ensuing decades, structural and mechanistic studies
      have substantially altered this initial viewpoint. Whereas self-splicing
      ribozymes clearly rely on essential metal-ion cofactors, self-cleaving ribozymes
      seem to use nucleotide bases for their catalytic chemistry. Despite the overall
      differences in chemical features, both RNA and protein enzymes use similar
      catalytic strategies.

PMID- 15956980
TI  - Gene discovery by ribozyme and siRNA libraries.
AB  - Catalytic RNAs, also known as ribozymes, can be engineered to optimize their
      activities in the intracellular environment. The introduction of a library of
      active ribozymes into cells, and the subsequent screening for phenotypic changes,
      allows the rapid identification of gene function. For the determination of gene
      function, ribozyme technology complements another RNA-based tool that is based on
      libraries of small interfering RNAs.

PMID- 15956981
TI  - Crosstalk between RNA metabolic pathways: an RNOMICS approach.
AB  - Eukaryotic cells contain many different RNA species. Nuclear pre-mRNAs and
      cytoplasmic mRNAs carry genomic information to the protein synthesis machinery,
      whereas many stable RNA species have important functional roles. The mature,
      functional forms of these RNA species are generated by post-transcriptional
      processing, and evidence has been accumulating that there are functional links
      between the various processing pathways. This indicates that there are regulatory
      networks that coordinate different stages of RNA metabolism. This article
      describes the aims and results, to date, of the European RNOMICS project as an
      example of an integrated approach to investigate these links.

PMID- 15956982
TI  - Vector-based RNA interference against vascular endothelial growth factor-A
      significantly limits vascularization and growth of prostate cancer in vivo.
AB  - RNA interference technology is emerging as a very potent tool to obtain a
      cellular knockdown of a desired gene. In this work we used vector-based RNA
      interference to inhibit vascular endothelial growth factor (VEGF) expression in
      prostate cancer in vitro and in vivo. We demonstrated that transduction with a
      plasmid carrying a small interfering RNA targeting all isoforms of VEGF,
      dramatically impairs the expression of this growth factor in the human prostate
      cancer cell line PC3. As a consequence, PC3 cells loose their ability to induce
      one of the fundamental steps of angiogenesis, namely the formation of a tube-like
      network in vitro. Most importantly, our "therapeutic" vector is able to impair
      tumor growth rate and vascularization in vivo. We show that a single injection of
      naked plasmid in developing neoplastic mass significantly decreases microvessel
      density in an androgen-refractory prostate xenograft and is able to sustain a
      long-term slowing down of tumor growth. In conclusion, our results confirm the
      basic role of VEGF in the angiogenic development of prostate carcinoma, and
      suggest that the use of our vector-based RNA interference approach to inhibit
      angiogenesis could be an effective tool in view of future gene therapy
      applications for prostate cancer.

PMID- 15956983
TI  - Coexpression of CD40L and CD70 by semiallogenic tumor cells induces anti-tumor
      immunity.
AB  - The immune system is potentially qualified to detect and eliminate tumor cells,
      but various mechanisms developed by tumor cells allow tumor escape. Strategies
      selected to promote antitumor responses have included genetic modifications of
      tumor cells to induce expression of costimulatory molecules. Moreover,
      alloantigens can also act as strong enhancers of the immune response. In this
      work, we have associated the expression of two costimulatory members of the TNF
      superfamily, CD40L and CD70 along with an allogenic MHC Class I (H-2K(d))
      molecule expression on melanoma cells (B16F10, H-2(b)) to favor the antitumor
      immune response. B16F10 tumor growth slows significantly when CD40L and CD70 are
      coexpressed by tumor cells and the association with the allogenic molecule (H
      2K(d)) enhances this effect. Growth kinetics of mock and CD40L-CD70-H-2K(d)
      expressing B16F10 tumors in immunocompetent versus nu/nu and beige mice suggested
      that CD8(+) T lymphocytes and NK cells were involved in this antitumor immunity.
      A delay in mock tumor growth was observed when CD40L-CD70-H-2K(d)-expressing
      B16F10 cells and mock tumor cells were injected simultaneously and
      contralaterally. It was also shown that in vivo immunization of immunocompetent
      mice with CD40L-CD70-H-2K(d) B16F10 tumor cells improved the generation of
      cytotoxic lymphocytes against the wild-type melanoma cells expressing the
      syngenic MHC Class I molecule H-2K(b) (B16K1). These observations lay a path for
      new immunotherapeutic trials using semiallogenic fibroblasts expressing
      costimulatory molecules and tumor-associated antigens.

PMID- 15956984
TI  - Amoxapine as an atypical antipsychotic: a comparative study vs risperidone.
AB  - Amoxapine is marketed as an antidepressant. However, its in-vitro profile,
      receptor occupancy and preclinical effects are very similar to atypical
      antipsychotics. Amoxapine has also shown efficacy as an atypical antipsychotic in
      open trials. The objective of this study was to compare the antipsychotic and
      side effect profile of amoxapine and risperidone in a randomised assignment,
      standardized dosing, double-blind trial of acutely psychotic patients with
      schizophrenia. A total of 48 schizophrenic patients were enrolled and randomized
      in a double-blind 6-week trial to receive either risperidone (up to 5 mg/day) or
      amoxapine (up to 250 mg/day). Positive, negative, affective symptoms and motor
      side effects were measured using standardized weekly assessments. Prolactin
      levels were also determined at baseline and at the end of the study. A total of
      39 patients (amoxapine, n=22; risperidone, n=21) completed the trial. Both
      pharmacological treatments, amoxapine 228.0 mg/day (SD=34.6) and risperidone 4.5
      mg/day (SD=0.7), showed equivalent improvement in positive, negative, and
      depressive symptoms. Amoxapine was associated with less EPS and less prolactin
      elevation than risperidone. These data support previous reports about the
      efficacy of amoxapine as an atypical antipsychotic. Since amoxapine is off
      patent, it may be a valuable low-cost alternative to new atypical antipsychotics,
      particularly in low-income countries where the majority of the patients are still
      treated with typical antipsychotics.

PMID- 15956985
TI  - Prolonged central mu-opioid receptor occupancy after single and repeated
      nalmefene dosing.
AB  - The opioid antagonist nalmefene offers an alternative to traditional
      pharmacological treatments for alcoholism. The present study was designed to
      investigate the relationship between nalmefene plasma concentration and central
      mu-opioid receptor occupancy after a clinically effective dose (20 mg, orally).
      Pharmacokinetics and mu-opioid receptor occupancy of nalmefene after single and
      repeated dosing over 7 days was studied in 12 healthy subjects. Serial blood
      samples were obtained after both dosings, and pharmacokinetic parameters for
      nalmefene and main metabolites were determined. Central mu-opioid receptor
      occupancy of nalmefene was measured with positron emission tomography (PET) and
      [(11)C]carfentanil at four time points (3, 26, 50, 74 h) after both dosings.
      Nalmefene was rapidly absorbed in all subjects. The mean t(1/2) of nalmefene was
      13.4 h after single and repeated dosing. The accumulation of nalmefene and its
      main metabolites in plasma during the repeated dosing period was as expected for
      a drug with linear pharmacokinetics, and steady-state was reached for all
      analytes. Both nalmefene dosings resulted in a very high occupancy at mu-opioid
      receptors (87-100%), and the decline in the occupancy was similar after both
      dosings but clearly slower than the decline in the plasma concentration of
      nalmefene or metabolites. High nalmefene occupancy (83-100%) persisted at 26 h
      after the dosings. The prolonged mu-opioid receptor occupancy by nalmefene
      indicates slow dissociation of the drug from mu-opioid receptors. These results
      support the rational of administering nalmefene when needed before alcohol
      drinking, and they additionally suggest that a high mu-opioid receptor occupancy
      can be maintained when nalmefene is taken once daily.

PMID- 15956986
TI  - Characterization of the rapid-onset type of behavioral sensitization to
      amphetamine in mice: role of drug-environment conditioning.
AB  - A rapid-onset type of behavioral sensitization (ROBS) has been demonstrated in
      rats treated with a single 'priming' injection of amphetamine (AMP). In that
      species, however, this phenomenon was restricted to AMP-induced stereotyped
      behavior (SB), not occurring for the locomotor-stimulant effect (LSE) of AMP and
      not reflecting environment-specific sensitization. In the present study, the ROBS
      was characterized in the mouse. Mice received a single 'priming' intraperitoneal
      injection of 5.0 mg/kg AMP which was paired or not with environment. At different
      intervals (3, 4 or 5 h) subgroups were tested for AMP (1.5 or 5.0 mg/kg)-induced
      SB or AMP (1.5 mg/kg)-induced open-field LSE. Results showed that: (1) in the
      absence of drug-environment association, a priming injection of AMP increased the
      SB induced by a 1.5 mg/kg AMP challenge injection given 3 h (but not 4 or 5 h)
      later; (2) when the dose of AMP challenge injection was increased to 5.0 mg/kg,
      an enhancement of SB was verified at all the intervals tested (3, 4, and 5 h);
      (3) when animals were tested in an open field, the priming injection of AMP
      produced an increase in the LSE of a 1.5 mg/kg AMP challenge injection, given 4 h
      later; (4) drug-environment association increased both SB and locomotion after a
      saline challenge injection and potentiated the rapid-onset sensitization of both
      behaviors in AMP-challenged mice. Collectively, these results demonstrate that
      the ROBS phenomenon also occurs in mice, is extended to AMP-induced LSE, and is
      markedly potentiated by (but does not depend on) environmental conditioning.

PMID- 15956987
TI  - Relationship of mania symptomatology to maintenance treatment response with
      divalproex, lithium, or placebo.
AB  - Euphoric and mixed (dysphoric) manic symptoms have different response patterns to
      divalproex and lithium in acute mania treatment, but have not been studied in
      relationship to maintenance treatment outcomes. We examined the impact of initial
      euphoric or dysphoric manic symptomatology on maintenance outcome. Randomized
      maintenance treatment with divalproex, lithium, or placebo was provided for 372
      bipolar I patients, who met improvement criteria during open phase treatment for
      an index manic episode. The current analysis grouped patients according to the
      index manic episode subtype (euphoric or dysphoric), and evaluated the impact on
      maintenance treatment outcome. The rate of early discontinuation due to
      intolerance during maintenance treatment was higher for initially dysphoric
      patients (N=249) than euphoric patients (N=123; 15.7 vs 7.3%, respectively;
      p=0.032). Both lithium (23.2%) and divalproex (17.1%) were associated with more
      premature discontinuations due to intolerance than placebo (4.8%; p=0.003 and
      0.02, respectively) in the initially dysphoric patients. Among initially euphoric
      patients, treatment with lithium was associated with significantly more premature
      discontinuations due to intolerance compared to placebo (18.2 vs 0%; p=0.03), and
      divalproex was significantly (p=0.05) more effective than lithium, but not
      placebo in delaying time to a depressive episode. Initial euphoric mania appeared
      to predispose to better outcomes on indices of depression and overall function
      with divalproex maintenance than with either placebo or lithium. Dysphoric mania
      appeared to predispose patients to more side effects when treated with either
      divalproex or lithium during maintenance therapy.

PMID- 15956988
TI  - COMT polymorphisms and anxiety-related personality traits.
AB  - High neuroticism and low extraversion are characteristic of anxiety-prone
      individuals. A functional variant in the catechol-O-methyltransferase (COMT)
      gene, the Val158Met ('val/met') polymorphism, has been associated in some prior
      studies with several phenotypes, including neuroticism. We tested the hypothesis
      that the val158met polymorphism would be associated with both high neuroticism
      and low extraversion, making it a plausible candidate locus for anxiety
      susceptibility. To determine whether val158met is responsible for these effects,
      we also evaluated the association with haplotypes that included two other SNPs
      within the COMT gene. We collected a sample of 497 undergraduate college students
      who were phenotyped on a personality inventory (the NEO-Personality Inventory
      Raised (NEO-PI-R)). Subjects were genotyped for three COMT polymorphisms: the
      well-studied nonsynonymous SNP rs4680 that generates a valine-to-methionine
      substitution (val158met), rs737865 (near exon #1), and rs165599 (also functional,
      near the 3'-UTR). Together, these three SNPs define a haplotype that is
      associated with reduced COMT expression in human brain. Logistic regression
      analyses were used to examine the effects of individual SNPs on extraversion and
      neuroticism scores. Score tests for association between these traits
      (quantitatively and dichotomously considered) and haplotypes were also conducted.
      We evaluated potential for population stratification artifact by genotyping a set
      of 36 unlinked highly polymorphic markers previously demonstrated to distinguish
      sufficiently ancestry of major American populations. Two of the SNPs (rs4680
      ('val/met') and rs737865) were significantly associated with (low) extraversion
      and, less consistently, with (high) neuroticism, with effects confined to women.
      A significant association between COMT haplotype and (low) extraversion and
      (high) neuroticism was also observed. Formal testing showed that population
      structure did not explain the findings. These data suggest that involvement of
      the COMT locus in susceptibility to anxiety-related traits (ie low extraversion
      and high neuroticism) is unlikely to be wholly accounted for by the well-studied
      rs4680 ('val/met') polymorphism. Other functional variants may exist that
      contribute to this relationship. Possible sex-specific effects remain to be
      further studied and explained.

PMID- 15956990
TI  - Association study of a monoamine oxidase a gene promoter polymorphism with major
      depressive disorder and antidepressant response.
AB  - Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of
      biogenic amines, may be implicated in the pathogenesis of major depressive
      disorder (MDD) and be related to the therapeutic effects of antidepressants. To
      elucidate a genetic predisposition of MDD, we studied a variable-number-tandem
      repeat (VNTR) polymorphism in the promoter region of the MAOA gene in a Chinese
      population of 230 MDD patients and 217 controls. We also examined the association
      of this polymorphism and antidepressant therapeutic response in the MDD patients
      who underwent a 4-week fluoxetine treatment. Our results showed a significantly
      increased frequency of 4-repeat (4R) allele in MDD patients, especially in the
      female population. Furthermore, MDD female patients who were 3R homozygotes had a
      significantly better response to 4-week fluoxetine treatment when compared to 4R
      carriers (p=0.024), but there was a nonsignificant difference found in male
      patients (p=0.081). Since the 4R allele transcribed 2-10 times more efficiently
      than those with 3R allele, our findings suggest that the MAOA-uVNTR may be
      involved in the pathogenesis of MDD and the antidepressant therapeutic mechanisms
      in Chinese population, and that there may be a gender effect in this association.

PMID- 15956989
TI  - Self-administered heroin and cocaine combinations in the rat: additive
      reinforcing effects-supra-additive effects on nucleus accumbens extracellular
      dopamine.
AB  - The concurrent use of cocaine and opiate combinations (speedball) has increased
      since the 1970s and now represents a growing subset of intravenous drug abusers.
      An isobolographic analysis was applied to the ascending limb of the dose-effect
      curves for rat self-administration of cocaine, heroin, and their combination to
      determine the nature of the interaction. The addition of heroin to cocaine
      shifted the dose-effect curve for self-administration to the left, and the
      modulation in reinforcing efficacy of the combination of cocaine and heroin was
      found to be additive. A second experiment used microdialysis to determine the
      effects of this drug combination on nucleus accumbens (NAc) extracellular levels
      of dopamine ([DA](e)) in rats self-administering low doses of cocaine, heroin, or
      cocaine/heroin combinations. These doses of cocaine and cocaine/heroin
      combinations significantly increased NAc [DA](e), while heroin alone did not. The
      ratio of the % baseline of [DA](e) (or the dialysate concentrations of DA) to
      cocaine in the dialysate was higher during self-administration of cocaine/heroin
      combinations than with cocaine alone. These data indicate that although the
      interaction between cocaine and heroin in maintaining self-administration is
      additive, a potentiation of NAc dopaminergic neurotransmission is present,
      suggesting that NAc [DA](e) may not be a direct measure of reinforcing efficacy
      and/or it is not central to the mediation of the self-administration of this drug
      combination.

PMID- 15956991
TI  - Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b
      receptor knockout mice: reversal by antipsychotic drugs.
AB  - In the present study, we investigated whether mice lacking the arginine
      vasopressin (AVP) V1b receptor (V1bR) exhibit deficits of prepulse inhibition
      (PPI) of the startle reflex, reminiscent of the sensorimotor gating deficits
      observed in a large majority of schizophrenic patients. V1bR knockout (KO) mice
      displayed significantly reduced levels of PPI of the startle reflex. In addition
      to PPI deficits, V1bR KO mice showed increased acoustic startle response.
      However, acoustic startle response was not significantly correlated to the PPI of
      the startle reflex in V1bR KO mice. V1bR KO mice also showed a decrease in basal
      levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is
      thought to be an important brain region for PPI. Moreover, PPI deficits observed
      in the V1bR KO mice are significantly reversed by atypical antipsychotics such as
      risperidone and clozapine but not by a typical neuroleptic haloperidol, like in
      schizophrenic patients. By contrast, we did not observe any significant
      differences between V1bR KO mice and wild-type mice in the open-field,
      light/dark, elevated plus maze, and forced swimming tests. The results of the
      present study indicate that V1bR may be involved in the regulation of PPI of the
      startle reflex. The V1bR has been considered an important molecular target for
      the development of antipsychotic drugs.

PMID- 15956992
TI  - Constitutively active micro opioid receptors mediate the enhanced conditioned
      aversive effect of naloxone in morphine-dependent mice.
AB  - Naloxone administration produces a robust conditioned place aversion (CPA) in
      opiate-naive rodents by blocking the action of enkephalins at mu opioid
      receptors. This aversive response is potentiated by prior exposure to morphine.
      In vitro studies indicate that morphine treatment may promote constitutive
      activity of mu opioid receptors. We hypothesized that such enhanced constitutive
      activity in vivo may underlie the increased aversive property of naloxone by
      uncovering the inverse agonist property of this drug. The CPA produced by
      naloxone was compared with that produced by the neutral antagonists 6-alpha- and
      6-beta-naloxol in mice with and without prior morphine exposure. While all three
      drugs produced CPA, only naloxone CPA was enhanced by morphine given 20 h prior
      to each naloxone injection. Furthermore, only naloxone produced withdrawal
      jumping when given 20 h after morphine, even though 6-alpha-naloxol was able to
      produce jumping when given 4 h after morphine. These data suggest that morphine
      may enhance naloxone CPA by increasing levels of constitutively active mu
      receptors and further support the role of such constitutive activity in mediating
      naloxone-precipitated physical withdrawal. Such long-term changes in constitutive
      activity of the mu receptor induced by exogenous opiate exposure may thus be an
      important factor in hedonic homeostatic dysregulation proposed to underlie the
      addictive process.

PMID- 15956993
TI  - Heightened cocaine and food self-administration in female rats with neonatal
      isolation experience.
AB  - Previously, we demonstrated that the early life stress of neonatal isolation
      facilitates acquisition of cocaine and food self-administration in adult female
      rats. We now test whether it enhances responding for these reinforcers after
      operant performance is established. Adult female rats were derived from litters
      that were either subjected to neonatal isolation (1 h/day isolation; postnatal
      days 2-9) or were nonhandled and assigned to one of two experiments. In
      Experiment 1, female rats well trained to self-administer cocaine were tested
      under a fixed-ratio 3 (FR3) schedule with several cocaine doses (0.0625-1.0
      mg/kg/infusion) and under a progressive-ratio (PR) schedule (0, 0.5, and 1.0
      mg/kg/infusion cocaine). In Experiment 2, female rats well trained to respond for
      food reinforcers under an FR15 schedule were tested under two PR schedules.
      Results show that neonatal isolation enhanced responding for cocaine under both
      schedules of reinforcement and increased responding for food under a PR schedule
      of reinforcement. These data extend our previous acquisition study in female rats
      to show that neonatal isolation enhances responding under maintenance conditions.
      These enduring behavioral changes may relate to the ability of neonatal isolation
      to increase striatal dopamine responses to psychostimulants, effects we showed
      previously in infant and juvenile rats. Neuropsychopharmacology (2006) 31, 70-76.
      doi:10.1038/sj.npp.1300779; published online 1 June 2005.

PMID- 15956994
TI  - Neurochemical, electrophysiological and pharmacological profiles of the selective
      inhibitor of the glycine transporter-1 SSR504734, a potential new type of
      antipsychotic.
AB  - Noncompetitive N-methyl-D-aspartate (NMDA) blockers induce schizophrenic-like
      symptoms in humans, presumably by impairing glutamatergic transmission.
      Therefore, a compound potentiating this neurotransmission, by increasing
      extracellular levels of glycine (a requisite co-agonist of glutamate), could
      possess antipsychotic activity. Blocking the glycine transporter-1 (GlyT1)
      should, by increasing extracellular glycine levels, potentiate glutamatergic
      neurotransmission. SSR504734, a selective and reversible inhibitor of human, rat,
      and mouse GlyT1 (IC50=18, 15, and 38 nM, respectively), blocked reversibly the ex
      vivo uptake of glycine (mouse cortical homogenates: ID50: 5 mg/kg i.p.), rapidly
      and for a long duration. In vivo, it increased (minimal efficacious dose (MED): 3
      mg/kg i.p.) extracellular levels of glycine in the rat prefrontal cortex (PFC).
      This resulted in an enhanced glutamatergic neurotransmission, as SSR504734
      potentiated NMDA-mediated excitatory postsynaptic currents (EPSCs) in rat
      hippocampal slices (minimal efficacious concentration (MEC): 0.5 microM) and
      intrastriatal glycine-induced rotations in mice (MED: 1 mg/kg i.p.). It
      normalized activity in rat models of hippocampal and PFC hypofunctioning (through
      activation of presynaptic CB1 receptors): it reversed the decrease in
      electrically evoked [3H]acetylcholine release in hippocampal slices (MEC: 10 nM)
      and the reduction of PFC neurons firing (MED: 0.3 mg/kg i.v.). SSR504734
      prevented ketamine-induced metabolic activation in mice limbic areas and reversed
      MK-801-induced hyperactivity and increase in EEG spectral energy in mice and
      rats, respectively (MED: 10-30 mg/kg i.p.). In schizophrenia models, it
      normalized a spontaneous prepulse inhibition deficit in DBA/2 mice (MED: 15 mg/kg
      i.p.), and reversed hypersensitivity to locomotor effects of d-amphetamine and
      selective attention deficits (MED: 1-3 mg/kg i.p.) in adult rats treated
      neonatally with phencyclidine. Finally, it increased extracellular dopamine in
      rat PFC (MED: 10 mg/kg i.p.). The compound showed additional activity in
      depression/anxiety models, such as the chronic mild stress in mice (10 mg/kg
      i.p.), ultrasonic distress calls in rat pups separated from their mother (MED: 1
      mg/kg s.c.), and the increased latency of paradoxical sleep in rats (MED: 30
      mg/kg i.p.). In conclusion, SSR504734 is a potent and selective GlyT1 inhibitor,
      exhibiting activity in schizophrenia, anxiety and depression models. By targeting
      one of the primary causes of schizophrenia (hypoglutamatergy), it is expected to
      be efficacious not only against positive but also negative symptoms, cognitive
      deficits, and comorbid depression/anxiety states.

PMID- 15956995
TI  - Increased pituitary volume in antipsychotic-free and antipsychotic-treated
      patients of the AEsop first-onset psychosis study.
AB  - Subjects at their first psychotic episode show an enlarged volume of the
      pituitary gland, but whether this is due to hypothalamic-pituitary-adrenal (HPA)
      axis hyperactivity, or to stimulation of the prolactin-secreting cells by
      antipsychotic treatment, is unclear. We measured pituitary volume, using 1.5-mm,
      coronal, 1.5 T, high-resolution MRI images, in 78 patients at the first psychotic
      episode and 78 age- and gender-matched healthy controls. In all, 18 patients were
      antipsychotic-free (12 of these were antipsychotic-naive), 26 were receiving
      atypical antipsychotics, and 33 were receiving typical antipsychotics. As
      hypothesized, patients had a larger pituitary volume than controls (+22%, p<
      0.001). When divided by antipsychotic treatment, and compared to controls, the
      pituitary volume was 15% larger in antipsychotic-free patients (p=0.028), 17%
      larger in patients receiving atypicals (p=0.01), and 30% larger in patients
      receiving typicals (p<0.001). Patients receiving typicals not only had the
      largest pituitary volume compared to controls but also showed a trend for a
      larger pituitary volume compared to the other patients grouped together (+11%,
      p=0.08). When divided by diagnosis, and compared to controls, the pituitary
      volume was 24% larger in patients with schizophrenia/schizophreniform disorder
      (n=40, p<0.001), 19% larger in depressed patients (n=13, p=0.022), 16% larger in
      bipolar patients (n=16, p=0.037), and 12% larger in those with other psychoses
      (n=9, p=0.2). In conclusion, the first-episode of a psychotic disorder is
      associated with a larger pituitary independently of the presence of antipsychotic
      treatment, and this could be due to activation of the HPA axis. Typical
      antipsychotics exert an additional enlarging effect on pituitary volume, likely
      to be related to activation of prolactin-secreting cells. This activation of the
      hormonal stress response could participate to the important metabolic
      abnormalities observed in patients with psychosis.

PMID- 15956996
TI  - Lithium- and valproate-induced alterations in circadian locomotor behavior in
      Drosophila.
AB  - Lithium and valproate are commonly used mood stabilizers, but their action
      pathways are not clearly understood. They also suffer from multiple toxic effects
      that limit their utility. Elucidating their action mechanisms could lead to newer
      agents and better understanding of the etiopathogenesis of bipolar disorder. We
      have expanded the study of signaling mechanisms of lithium and valproate by using
      Drosophila circadian locomotor activity as a robust behavioral assay that is
      amenable to genetic manipulations. We demonstrate that lithium affects the
      circadian system of Drosophila similarly to what has been reported in the
      mammalian studies. We show that lithium and valproate share effects on the
      circadian locomotor activity of Drosophila: they lengthen the period of circadian
      rhythms and increase arrhythmicity. Valproate exerts these effects in a weaker
      fashion than does lithium. We also tested the circadian alterations in multiple
      mutant lines of Drosophila bearing defects in the GSK-3beta gene and other clock
      genes in response to lithium administration. We show that lithium partially
      rescues the shortening of circadian period when the GSK-3beta gene is
      overexpressed only in specific circadian pacemaker neurons, thus implicating GSK
      3beta as a component in lithium's effect on the circadian oscillator. Moreover,
      lithium also lengthens the period in GSK-3beta heterozygous mutants and
      doubletime long mutants. These results establish a basis for using Drosophila
      genetics to investigate more fully lithium and valproate action mechanisms.

PMID- 15956998
TI  - Effect of vitamin supplementation to HIV-infected pregnant women on the
      micronutrient status of their infants.
AB  - OBJECTIVE: We examined whether supplementation with vitamin A and/or vitamins B,
      C, and E to HIV-infected women during pregnancy and lactation is related to
      increased concentrations of vitamins A, B12, and E in their infants during the
      first 6 months of life. DESIGN: We carried out a randomized clinical trial among
      716 mother-infant pairs in Dar-es-Salaam, Tanzania. Women were randomly allocated
      to receive a daily oral dose of one of four regimens: vitamin A, multivitamins
      (B, C, and E), multivitamins including A, or placebo. Supplementation started at
      first prenatal visit and continued after delivery throughout the breastfeeding
      period. The serum concentration of vitamins A, E and B12 was measured in infants
      at 6 weeks and 6 months postpartum. RESULTS: Maternal vitamin A supplementation
      increased serum retinol in the infants at 6 weeks (mean difference=0.09
      micromol/l, P<0.0001) and 6 months (mean difference=0.06 micromol/l, P=0.0002),
      and decreased the prevalence of vitamin A deficiency, but had no impact on serum
      vitamins E or B12. Multivitamins increased serum vitamin B12 at 6 weeks and 6
      months (mean differences=176 pmol/l, P<0.0001 and 127 pmol/l, P<0.0001,
      respectively) and vitamin E (mean differences=1.8 micromol/l, P=0.0008 and 1.1
      micromol/l, P=0.004, respectively) and decreased the prevalence of vitamin B12
      deficiency. CONCLUSIONS: Vitamin supplementation to HIV-1-infected women is
      effective in improving the vitamin status of infants during the first 6 months of
      age.

PMID- 15956997
TI  - Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in
      mice.
AB  - Enhancing cholinergic function has been suggested as a possible strategy for
      ameliorating the cognitive deficits of schizophrenia. The purpose of this study
      was to examine the effects of acetylcholinesterase (AChE) inhibitors in mice
      treated with the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist,
      MK-801, which has been suggested as an animal model of the cognitive deficits of
      schizophrenia. Three separate experiments were conducted to test the effects of
      physostigmine, donepezil, or galantamine on deficits in learning and memory
      induced by MK-801. In each experiment, MK-801 (0.05 or 0.10 mg/kg) or saline was
      administered i.p. 20 min prior to behavioral testing over a total of 12 days. At
      30 min prior to administration of MK-801 or saline, one of three doses of the
      AChE inhibitor (ie physostigmine-0.03, 0.10, or 0.30 mg/kg; donepezil-0.10, 0.30,
      or 1.00 mg/kg; or galantamine-0.25, 0.50, or 1.00 mg/kg) or saline was
      administered s.c. Behavioral testing was performed in all experimental animals
      using the following sequence: (1) spatial reversal learning, (2) locomotion, (3)
      fear conditioning, and (4) shock sensitivity. Both doses of MK-801 produced
      impairments in spatial reversal learning and in contextual and cued memory, as
      well as hyperlocomotion. Physostigmine and donepezil, but not galantamine,
      ameliorated MK-801-induced deficits in spatial reversal learning and in
      contextual and cued memory in a dose-dependent manner. Also, physostigmine, but
      not donepezil or galantamine, reversed MK-801-induced hyperlocomotion.
      Galantamine, but not physostigmine or donepezil, altered shock sensitivity. These
      results suggest that AChE inhibitors may differ in their capacity to ameliorate
      learning and memory deficits produced by MK-801 in mice, which may have relevance
      for the cognitive effects of cholinomimetic drugs in patients with schizophrenia.

PMID- 15956999
TI  - Pedigree construction and disease confirmation: a pilot study in Wales exploring
      the role of nonclinical personnel.
AB  - Pedigree construction and disease confirmation are the means by which reported
      family histories are translated into a verified clinical tool informing risk
      assessment and management decisions by clinical genetics staff. In this study, we
      hypothesised that pedigree generation data processes do not generally require the
      clinical expertise of genetic counsellors and that they could be successfully
      transferred to nonclinical data administrators. We made a pragmatic comparison of
      two processes of pedigree generation by different personnel from 14 consecutive
      family history questionnaires containing 88 living and decease affected
      individuals. The pedigrees generated by the genetic counsellor and the data
      administrator were compared; discrepancies were quantified and their source
      determined. The information gathered by the data administrator mirrored that of
      the genetic counsellors in 89% of cases. Time was saved by permitting direct
      access to cancer registry and local oncology centre databases. Constructing a
      pedigree is not always a case of transferring clear-cut data. Decisions need to
      be made about which cancers to confirm. Notable differences emerged in the number
      of pieces of information not transferred. Ambiguous information was often
      interpreted differently, suggesting the need for clinical staff to review
      pedigrees after their initial plotting by the data administrator. This study
      demonstrates a good degree of concordance between pedigrees constructed by a
      nonclinical data administrator and those of experienced genetic counsellors.
      However, the redirection of all pedigree activity to nonclinical personnel up to
      the point of risk review is not possible at present.

PMID- 15957000
TI  - Combining the case-control methodology with the small size
      transmission/disequilibrium test for multiallelic markers.
AB  - Case-control studies compare marker-allele distributions in affected and
      unaffected individuals, and significant results may be due to linkage but can
      also simply reflect population structure. To test for linkage after obtaining a
      significant case-control finding, within-family analysis can be performed. In a
      transmission/disequilibrium test (TDT), genotypes of cases are compared to those
      of their parents to explore whether a specific allele, or marker, at a locus of
      interest is transmitted to a greater degree than Mendelian inheritance would
      warrant. For multiallelic markers, several authors have proposed extensions to
      the TDT. In this article, we propose a TDT test, utilizing the available
      information of a case-control study in the grouping of alleles for multiallelic
      markers, and thereby increase the statistical power of a TDT test with a small
      sample size.

PMID- 15957001
TI  - Male-to-male transmission of X-linked Alport syndrome in a boy with a 47,XXY
      karyotype.
AB  - Alport syndrome (AS) is a genetically heterogeneous renal hereditary disease.
      Male-to-male transmission has been considered fully indicative of autosomal
      dominant AS. We report a family with male-to-male transmission of X-linked AS due
      to an extra X chromosome of paternal origin in the proband. Linkage analysis
      excluded the autosomal loci and demonstrated segregation with the COL4A5 locus
      (Xq22.3). Sperm FISH analysis from his father detected an increased XY disomy.
      Mutation screening of the COL4A5 gene identified a splicing mutation, c.4688G>A.
      The proband and his paternal grandmother showed random X chromosome inactivation.
      However, a preferential expression of the aberrantly spliced transcript was
      detected in the proband when compared to his grandmother. This finding could
      explain why the AS phenotype of this 47,XXY boy resembles more an affected male
      than a female carrier. This is the first reported case of concurrence of Alport
      and Klinefelter syndromes.

PMID- 15957002
TI  - Communication of pharmacogenetic research results to HIV-infected treated
      patients: standpoints of professionals and patients.
AB  - The aim of pharmacogenetic studies is to adapt therapeutic strategies to
      individual genetic profiles, thus maximising their efficacy and minimising the
      likelihood of adverse side effects. Since the advent of personalised medicine,
      the issue of communicating research results to participants has become
      increasingly important. We addressed this question in the context of HIV
      infection, as patients and associations are particularly concerned by research
      and therapeutic advances. We explored the standpoints of both research
      professionals and participants involved in a pharmacogenetic study conducted in a
      cohort of HIV-infected patients. The setting of the research protocol was
      followed over a 2-year period. Participants' standpoints were collected through a
      questionnaire and interviews were conducted with research professionals. Of 125
      participants, 76% wished to receive individual results and 71% wished to receive
      collective results; 39% did not know when results might be expected.
      Communication of global research results is a principle that is generally
      accepted by professionals. Concerning individual feedback, the professionals felt
      that it was necessary if it could be of direct benefit to the participant, but
      they expressed doubts for situations with no recognised benefit. Our results
      highlight the necessity to consider this issue in greater detail. We suggest the
      need to anticipate the debates concerning individual feedback, to differentiate
      between situations and the importance of further investigations on the
      opportunities and modalities of communication. Finally, our work emphasised the
      opposite pressures between the pursuit of scientific knowledge and the
      therapeutic orientation of clinical trials.

PMID- 15957003
TI  - Scoring proteomes with proteotypic peptide probes.
AB  - Technologies for genome-wide analyses typically undergo a transition from a
      discovery phase to a scoring phase. In the discovery phase, the genomic universe
      is explored and all pertinent data are noted. In the scoring phase, relevant
      entities are screened to reveal groups of genes that are associated with specific
      biological processes or conditions. In this article, we propose that the
      transition from a discovery to a scoring phase is also essential, feasible and
      imminent for proteomics.

PMID- 15957004
TI  - Controlling nuclear receptors: the circular logic of cofactor cycles.
AB  - Nuclear receptors regulate many biologically important processes in development
      and homeostasis by their bimodal function as repressors and activators of gene
      transcription. A finely tuned modulation of the transcriptional activities of
      nuclear receptors is crucial for determining highly specific and diversified
      programmes of gene expression. Recent studies have provided insights into the
      molecular mechanisms that are required to switch between repression and
      activation functions, the combinatorial roles of the multiple cofactor complexes
      that are required for mediating transcriptional regulation, and the central
      question of how several different signalling pathways can be integrated at the
      nuclear level to achieve specific profiles of gene expression.

PMID- 15957005
TI  - Biological implications of cell fusion.
AB  - Until recently, cells were thought to be integral and discrete components of
      tissues, and their state was determined by cell differentiation. However, under
      some conditions, stem cells or their progeny can fuse with cells of other types,
      mixing cytoplasmic and even genetic material of different (heterotypic) origins.
      The fusion of heterotypic cells could be of central importance for development,
      repair of tissues and the pathogenesis of disease.

PMID- 15957006
TI  - A reduced rate of in vivo dopamine transporter binding is associated with lower
      relative reinforcing efficacy of stimulants.
AB  - A slow onset of action has been hypothesized to weaken the reinforcing effects of
      drugs. The present study evaluated this hypothesis with slow-onset cocaine
      analogs, WIN 35428, RTI 31, and RTI 51. When cocaine or a cocaine analog was made
      available to rhesus monkeys (n = 4 or 5) for self-administration under a
      progressive-ratio (PR) schedule with a 1-h time-out between injections, all the
      drugs functioned as positive reinforcers. The maximum number of injections was in
      the order of cocaine > WIN 35428 > RTI 31 > RTI 51. In in vivo binding in rat
      striatum, equipotent doses of cocaine, WIN 35428, RTI 31, and RTI 51 were
      estimated to displace 25% of [(3)H]WIN 35428 binding at the dopamine transporters
      (DAT), respectively, 5.8, 22.4, 30.8, and 44.1 min after the intravenous
      injection. Further, relative reinforcing efficacy was correlated with rate of DAT
      binding such that slower displacement of [(3)H]WIN 35428 was associated with a
      weaker reinforcing effect. In in vitro binding in monkey brain tissue, the
      cocaine analogs had higher affinity for monoamine transporter sites, but similar
      affinity ratios of 5-HTT/DAT, compared to cocaine. Lastly, RTI 31 was shown to
      function as a positive reinforcer in drug-naive rhesus monkeys under a fixed
      ratio 1 schedule. Collectively, the data support the hypothesis that a slow onset
      at the DAT is associated with reduced reinforcing efficacy of DAT ligands. The
      data under both the PR and FR schedules, however, suggest that a slow onset at
      the DAT influence reinforcing effect only to a limited extent.

PMID- 15957007
TI  - Effects of SCH-23390 infused into the amygdala or adjacent cortex and basal
      ganglia on cocaine seeking and self-administration in rats.
AB  - Amygdala D1 receptors have been implicated in the motivating effects of cocaine
      conditioned cues and cocaine itself, but the specific nucleus involved is
      unclear. Thus, we infused the D1 antagonist, SCH-23390, into the rostral
      basolateral amygdala (rBLA), caudal basolateral amygdala (cBLA), or central
      amygdala (CEA), and tested its effects on self-administration of cocaine, as well
      as reinstatement of extinguished cocaine-seeking behavior by cocaine-conditioned
      cues or cocaine itself. Two anatomical controls, the posterior regions of basal
      ganglia (BG) and somatosensory/insular cortices (CTX), were also examined.
      Cocaine self-administration was increased and cue and cocaine reinstatement were
      decreased by SCH-23390 infusion into every region when examined across the hour
      test session, with the exception that cBLA infusion did not alter cocaine
      reinstatement. In the first 20 min of the session, when SCH-23390 was more
      localized in the target sites, self-administration was increased by infusion into
      the CEA, cBLA, BG, and CTX, with lesser increases in the rBLA. Cocaine
      reinstatement was attenuated during the first 20 min only by infusion into the
      CEA, rBLA, and CTX. Cue reinstatement was not reliably observed in the first 20
      min, but there was a trend for attenuation by infusion into the cBLA, and
      surprisingly, significant attenuations in the BG and CTX. The findings suggest
      that D1 receptors in subregions of the amygdala play differential roles in the
      reinforcing/motivational effects of cocaine, while the cue reinstatement effects
      are less clear. Further research is needed to examine the novel findings that
      neighboring regions of the BG and CTX may play a role in motivation for cocaine.

PMID- 15957009
TI  - The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in
      cholinergic and serotonergic models of memory deficiency in the rat.
AB  - Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of
      learning and memory. Although the underlying mechanism(s) are not well
      understood, these effects may involve an increase in acetylcholine (ACh) levels.
      The present study sought to characterize the cognitive-enhancing effects of the 5
      HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H
      indole) in a rat object recognition task employing a cholinergic (scopolamine
      pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model,
      and compared its pattern of action with that of the acetylcholinesterase
      inhibitor metrifonate. Initial testing in a time-dependent forgetting task
      employing a 24-h delay between training and testing showed that metrifonate
      improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was
      inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and
      metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by
      scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively).
      In conclusion, although Ro4368554 did not improve a time-related retention
      deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting
      that both mechanisms may be involved in the facilitation of object memory by
      Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.

PMID- 15957008
TI  - Risperidone pretreatment prevents elevated locomotor activity following neonatal
      hippocampal lesions.
AB  - Long-standing behavioral abnormalities emerge after puberty in rats following
      neonatal hippocampal lesion, providing a developmental model of abnormal rat
      behavior that may have predictive validity in identifying compounds effective in
      treating symptoms of schizophrenia. We sought to test the predictive validity of
      the neonatal hippocampal lesion model in identifying preventive treatment for
      first-episode psychosis. We determined the effect of risperidone, recently
      studied for prevention of first-episode psychosis, on the development of elevated
      locomotor activity following neonatal hippocampal lesions. Rat pups received
      hippocampal or sham lesions on postnatal day 7, followed by treatment with
      risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in
      response to novelty, amphetamine, and nocturnal locomotion were determined on
      postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented
      elevated locomotor activity in some, but not all, of the behavioral tasks
      following neonatal hippocampal lesions. In contrast, higher risperidone
      pretreatment was less effective in preventing elevated locomotor activity
      following neonatal hippocampal lesions. Because low risperidone dosages were also
      found to be effective in preventing first-episode psychosis in human studies,
      these data support the predictive validity of the hippocampal lesion model in
      identifying medications for prevention of first-episode psychosis. Additionally,
      these data support the use of low-dose risperidone in psychosis prevention, and
      suggest the possibility that higher risperidone doses could be less effective in
      this application.

PMID- 15957010
TI  - [Cognition in dysthymia].
AB  - Depression is named as one of the most prevalent Mental Health problem, affecting
      almost 10 % of the population. According to Diagnostic and Statistical Manual of
      Mental Disorders (DSM-IV) different subtypes are included. Dysthymic Disorder is
      characterized by a depressed mood for most of the day, for more days than not, as
      indicated either by subjective account or observation by others, for at least 2
      years. The aim of this study was to investigate the neuropsychological profile of
      dysthymic disorder. Ninety three patients fulfilling criteria for dysthymia were
      examined on a variety of cognitive tasks, neurological exam and a semi-structured
      psychiatric interview. Forty one non-depressed individuals served as controls.
      Significant differences between groups were found in digit span; immediate and
      delayed recall of a story; and semantic and phonologic fluency. Logic memory was
      worse than serial learning task, and has a correlation with attention deficit and
      depressive features. CONCLUSIONS: This results indicate that the
      neuropsychological performance of patients with dysthymic disorder exhibit
      impairments in attention and memory. Attentional deficits appear to be the key of
      cognitive deficits in dysthymia.

PMID- 15957011
TI  - [Empirical validation of theoretical models and cognitive behavioral treatments
      for Generalized Anxiety Disorder].
AB  - The present article reviews cognitive-behavioral treatments efficacy studies for
      Generalized Anxiety Disorder, as well as theoretical suppositions that underlie
      such treatment models. Efficacy studies, carried out during the last ten years,
      are analyzed. They have been grouped according to theoretical models. Finally,
      the investigations that test this theoretical hypothesis are analyzed. The search
      was carried out in MedLine, EBSCO, PubMed and PsycLIT databases. The efficacy
      reported showed a great variability of outcomes, which varied from 45 to 77%. The
      degree of theoretical validation also varies thoroughly among different
      intervention models. Findings implications regarding therapeutic recommendations
      are discussed, as well as theoretical hypotheses that, hardly investigated, could
      improve our understanding of the disorder.

PMID- 15957012
TI  - [Heteroaggressiveness' assessment].
AB  - In this article we describe topics associated with violence and aggressiveness.
      We review the psychological, social and neurobiological bases of aggressiveness
      according to different theoretical views. Different ideas about dangerousness are
      listed, and at the same time we try to delimit this term within the forensic
      psychiatric field. We classify different types of dangerousness and their
      relation with related psychiatric disorders. Finally, we locate dangerousness in
      the Civil and the Criminal Code and we supply scales for its assessment.

PMID- 15957013
TI  - [Assessment of dynamic violent behavior risk factors].
AB  - Dynamic violent behavior risk factors have special significance since they
      constitute the main target for preventive intervention. Different dynamic factors
      as well as violent recidivism were assessed with, among other instruments, the
      environmental risk (Risk Management) section of the Argentinean version of the
      HCR-20 in 25 parolees from the Province of Buenos Aires Penitentiary System.
      Among other findings, the prevalence of the risk factors linked to substance
      abuse and socioeconomic deprivation, and the heterogeneous perception of the
      official institutions are very significant. Exposure to destabilizers was the
      factor most associated with violent recidivism.

PMID- 15957014
TI  - [Assessment of suicide risk: clinical and legal aspects].
AB  - Suicide is a multicausal phenomena, that can be studied from different points of
      view. This article reviews suicide risk factors and legal issues and tries to
      give physicians a guide of procedures taking into account the current legal
      framework in Argentina.

PMID- 15957015
TI  - [Malingering in the clinical setting].
AB  - This article presents an overview of advances in the clinical and
      neuropsychological assessment of malingering, issues in diagnostic differential,
      neuropsychological and psychodynamic test methods, and special issues presented
      by medical - legal context, and other factors which may affect presentations.
      Cautions and recommendations for practice are presented.

PMID- 15957016
TI  - [Difficulties for the medical and legal forensic evaluation in cases of sexual
      abuse].
AB  - The forensic evaluation of sexual offenders and their victims are a very complex
      task. This concern becomes even more relevant when children have to be assessed.
      The evaluation process should consider: children's motivation to deceive during
      forensic assessment; their perception of the assessment process and its influence
      on their deceptive tendencies; parental issues related to dissimulation among
      children and the induction of false memories. The article summarize these
      problems and gives physicians a practical guide for managing this issue.

PMID- 15957017
TI  - [Aging and civil competence: medico-legal note. 1929].

PMID- 15957018
TI  - [Ethical aspects of psychiatric practice in Argentina: a survey].
AB  - The following paper is the last one of three, whose primary target consists of
      reflecting on the present psychiatric practice and about the ethical questions
      that of her are given off. We expose the results of a study, made from a survey
      to a population of psychiatrists of Argentina that investigate our intellectual
      and clinical reality. We describe the different characteristics, some of which we
      considered essential for the clinical practice and tried to determine the
      relevance that formation and readings in ethics have for the psychiatrists, along
      with the relevance granted to the social and anthropological aspects of our
      specialty at the moment of clinical attention.

PMID- 15957019
TI  - Fast, easy, clean chemistry by using water as a solvent and microwave heating:
      the Suzuki coupling as an illustration.
AB  - Water is an excellent solvent for organic chemistry and microwave heating offers
      a very efficient way of heating reaction mixtures. In this article, by focusing
      on the Suzuki reaction, it is shown how these two methods, used alone or
      together, can impact modern synthetic chemistry, making reactions faster, easier
      and cleaner.

PMID- 15957020
TI  - Delicious not siliceous: expanded carbohydrates as renewable separation media for
      column chromatography.
AB  - Expansion of native corn starch produces a high surface area mesoporous material
      capable of acting as a novel stationary phase for separating various mixtures of
      compounds.

PMID- 15957021
TI  - A novel class of phosphorescent gold(III) alkynyl-based organic light-emitting
      devices with tunable colour.
AB  - A novel class of luminescent cyclometalated gold(III) alkynyl complexes has been
      demonstrated to possess EL properties and has been employed in the roles of
      electrophosphorescent emitters or dopants of organic light-emitting diodes
      (OLEDs) with high brightness and efficiency.

PMID- 15957023
TI  - Ethene hydroformylation with CO/H2O: nucleophilic attack by water on to a
      terminal CO of a Ru(II) acylcarbonyl complex.
AB  - The reaction with water of acyldicarbonyl-Ru(II) complexes relevant to ruthenium
      catalysed ethene hydrocarbonylation with CO/H2O is shown to consist of a
      nucleophilic attack and to proceed via coordination of propionate and CO to the
      Ru(II) species.

PMID- 15957022
TI  - The use of a continuous flow-reactor employing a mixed hydrogen-liquid flow
      stream for the efficient reduction of imines to amines.
AB  - Imines have been reduced to amines in high yield, and with excellent
      chemoselectivity, by catalytic hydrogenation in a continuous flow-reactor,
      utilising an electrochemically-generated hydrogen source to produce a mixed
      hydrogen-liquid flow stream.

PMID- 15957024
TI  - Mechanochemical and solution reactions between AgCH3COO and [H2NC6H10NH2] yield
      three isomers of the coordination network {Ag[H2NC6H10NH2]+}infinity.
AB  - Solid-state co-grinding of silver acetate and solid trans-1,4-diaminocyclohexane,
      [H2NC6H10NH2] yields two isomeric coordination networks depending on the
      crystallization conditions; a third isomeric form is obtained when the same
      reaction is carried out in solution.

PMID- 15957025
TI  - Biological agent inactivation in a flowing air stream by photocatalysis.
AB  - The first decontamination of a flowing air stream polluted by bacteria, via room
      temperature non-germicidal UV photocatalysis on titania, leads to a simple and
      99.1-99.8% efficient process.

PMID- 15957026
TI  - Charge-transport in crystalline organic semiconductors with liquid crystalline
      order.
AB  - We report the design and synthesis of a liquid crystalline material exhibiting
      highly ordered smectic phases and high charge carrier-mobility; by a process
      known as "paramorphosis" highly ordered smectic phases can be transferred to the
      amorphous crystalline state on crystallisation without the formation of
      significant crystal grain boundaries and deep traps.

PMID- 15957027
TI  - Naked eye detection of anions by alkynyl-ruthenium exo-receptors: selective
      recognition of fluoride anion.
AB  - Alkynyl-ruthenium complexes bearing terminal hydrogen-bonding receptors act as
      efficient anion sensors exhibiting large guest-induced colour changes and show
      unexpectedly high selectivity to fluoride ions.

PMID- 15957028
TI  - Synthesis and characterisation of a {Ni21Ag} cage.
AB  - An unusual {Ni21Ag} cluster is reported and demonstrates the importance of
      examining the "counter-ion" present in all reactions involving polymetallic
      complexes.

PMID- 15957029
TI  - The synthesis of head-to-tail (H-T) dimers of 3-substituted thiophenes by the
      hypervalent iodine(III)-induced oxidative biaryl coupling reaction.
AB  - The head-to-tail (H-T) dimers could be obtained selectively by the oxidative
      coupling reaction of 3-substituted thiophenes using a combination of hypervalent
      iodine(III) reagents and trimethylsilyl trifluoromethanesulfonate.

PMID- 15957030
TI  - Selective photocatalytic reduction of nitrate to nitrogen molecules in an aqueous
      suspension of metal-loaded titanium(IV) oxide particles.
AB  - Nitrate was photocatalytically reduced to nitrogen molecules with a high
      selectivity in a basic aqueous suspension of palladium and copper-loaded
      titanium(IV) oxide powders in the presence of oxalate anion as a hole scavenger.

PMID- 15957031
TI  - Structure and anti-HIV activity of micrandilactones B and C, new nortriterpenoids
      possessing a unique skeleton from Schisandra micrantha.
AB  - Two new highly oxygenated nortriterpenoids with a unique norcycloartane skeleton,
      micrandilactones B and C, were isolated from Schisandra micrantha;
      micrandilactone C exhibited an EC50 value of 7.71 microg/mL (SI > 25.94) against
      HIV-1 replication with minimal cytotoxicity, and the potent anti-HIV-1 activity
      and unique structural features of make it a promising lead for therapeutic
      development of a new generation of anti-HIV drug.

PMID- 15957032
TI  - An unprecedented copper(I,II)-octacyanotungstate(V) 2-D network: crystal
      structure and magnetism of [CuII(tren)]{CuI[W(V)(CN)8]} . 1.5H2O.
AB  - A novel two-dimensional cyanide-bridged polymer [CuII(tren)]{CuI[W(V)(CN)8]} .
      1.5H2O (tren = tris(2-aminoethyl)amine) formed via the simultaneous in situ metal
      ligand redox reaction of [Cu(tren)(OH2)]2+ and self-assembly with [W(V)(CN)8]3-
      consists of a {CuI[W(V)(CN)8]} square grid built of CuI centres of tetrahedral
      geometry coordinatively saturated by CN bridges and [W(V)(CN)8]3- capped by
      [CuII(tren)]2+ moieties; it exhibits ferromagnetic coupling J1 = +5.8(1) cm(-1)
      within the CuII-W(V) dinuclear subunits and weak antiferromagnetic coupling J2 = 
      0.03(1) cm(-1) between them through diamagnetic CuI spacers.

PMID- 15957033
TI  - Sustainable Mizoroki-Heck reaction in water: remarkably high activity of Pd(OAc)2
      immobilized on reversed phase silica gel with the aid of an ionic liquid.
AB  - Palladium acetate immobilized on reversed phase amorphous silica gel with the aid
      of an ionic liquid, [bmim]PF6, was highly efficient in the promotion of the
      Mizoroki-Heck reaction in pure water without a ligand up to the sixth re-use, in
      95% average yield with TON and TOF 1,600,000 and 71,000 (h(-1)), respectively.

PMID- 15957034
TI  - Preparation and structure of novel siloxene nanosheets.
AB  - We demonstrate the two-dimensional silicon backbone structure of siloxene
      nanosheets, which produces relatively monodisperse nanosheets with a thickness of
      0.7 nm and lengths in the range 100-200 nm; the thickness is an order of
      magnitude smaller than that of previously reported silicon nanoparticles prepared
      by a variety of other methods.

PMID- 15957035
TI  - Replication of biological organizations through a supercritical fluid route.
AB  - A novel and simple method to replicate biological organizations (cotton and
      pollen grains) with high precision was proposed, in which the precursor dissolved
      in supercritical CO2 reacted with the surface active groups and adsorbed surface
      water on biological templates, followed by in situ SCF extraction of the
      byproducts and unreacted precursor, resulting in inorganic replicas faithfully
      copying both the macro- and microstructures of the biotemplates.

PMID- 15957036
TI  - High yield method for nanocrystalline zeolite synthesis.
AB  - Nanocrystalline zeolites, such as silicalite-1 and zeolite Y, were synthesized in
      high yield by periodically removing nanocrystals from the synthesis solution and
      recycling the unused reagents, including the template and T-atom sources.

PMID- 15957037
TI  - Ion transfer processes at ionic liquid based redox active drop deposited on an
      electrode surface.
AB  - Ion transfer across the boundary formed at an ionic liquid drop deposited on an
      electrode immersed in aqueous solution, generated by electrochemical redox
      reaction at the electrode-ionic liquid interface, is studied to obtain
      information about the ability of anions to be transferred into a room temperature
      ionic liquid.

PMID- 15957038
TI  - Carbocycles via enantioselective inter- and intramolecular iridium-catalysed
      allylic alkylations.
AB  - Carbocycles with > 90% ee were prepared via Ir-catalysed asymmetric allylic
      alkylation/ring closing metathesis sequences or enantioselective Ir-catalysed
      intramolecular allylic alkylations.

PMID- 15957039
TI  - Iron porphyrins anchored to a thermosensitive polymeric core-shell nanosphere as
      a thermotropic catalyst.
AB  - A thermosensitive nanocatalyst was prepared in the reaction of water-soluble
      iron(III) porphyrins and thermosensitive polymeric nanospheres with a core-shell
      structure; its catalytic activity in cyclohexene oxidation by iodosylbenzene was
      dependent markedly on reaction temperatures in aqueous solution.

PMID- 15957040
TI  - Selective separation of Am(III) from lanthanides(III) by solvent extraction with
      hydrophobic field of "superweak" anion.
AB  - The weakly coordinating hydrophobic anion TFPB-, whose surface is covered with a
      hydrophobic field, gives rise to a selective separation of Am(III) from
      lanthanides(III) in their solvent extraction even with a hard-donor extractant
      that shows no selectivity for Am(III) in traditional solvent extraction.

PMID- 15957041
TI  - Nafion-stabilized magnetic nanoparticles (Fe3O4) for [Ru(bpy)3]2+(bpy =
      bipyridine) electrogenerated chemiluminescence sensor.
AB  - A highly sensitive and stable [Ru(bpy)3]2+ ECL sensor has been fabricated based
      on the multilayer films of Nafion-stabilized magnetic nanoparticles
      (Nafion/Fe3O4) formed on a platinum electrode surface by means of an external
      magnet.

PMID- 15957042
TI  - In situ hybridization of PNA/DNA studied label-free by electrochemical impedance
      spectroscopy.
AB  - The in situ hybridization kinetics of label-free DNA on mixed monolayers of
      peptide nucleic acid (PNA) and 6-mercapto-1-hexanol (MCH) on Au electrodes was
      investigated by electrochemical impedance spectroscopy (EIS) and used to
      discriminate the fully complementary DNA from the single-base mismatched hybrids.

PMID- 15957043
TI  - Self-assembly of beta-D glucose-stabilized Pt nanocrystals into nanowire-like
      structures.
AB  - In this work we demonstrate the self-assembly of beta-D glucose-protected Pt
      nanocrystals (average particle size = 4.1 nm) into nanowire-like assemblies under
      ambient conditions.

PMID- 15957044
TI  - Thermal, pressure and light switchable spin-crossover materials.
AB  - This article reviews the most relevant chemical and structural aspects that
      influence the spin-crossover phenomenon (SCO). Special attention is focussed on
      the recent development of SCO coordination polymers. The different approaches
      currently being explored in order to achieve multifunctionality in SCO materials
      are discussed.

PMID- 15957045
TI  - Palladium-gold oxo complexes.
AB  - Treatment of L2PdCl2(L2= 4,4-di-tert-butyl-2,2-bipyridine) with [(L'Au)3(mu3
      O)]BF4(L'= PPh3) has yielded cationic oxo complexes with core formulas Pd2Au2O2
      and Pd4AuO3 thereby doubling the number of structurally characterized Pd oxo
      complexes.

PMID- 15957046
TI  - Assembly of a tri-silver metallo-capsule incorporating a tripodal tris-pyridyl
      ligand.
AB  - A trinuclear metallo-capsule has been assembled from a new tripodal pyridyl
      ligand and three silver(I) ions; the X-ray structure shows the presence of a Ag
      Ag interaction in the solid state giving rise to a non-symmetric capsule
      arrangement while NMR evidence indicates that the structure in solution is
      symmetrical.

PMID- 15957047
TI  - Synthesis of mono- and geminal dimetalated carbanions of
      bis(phenylsulfonyl)methane using alkali metal bases and structural comparisons
      with lithiated bis(phenylsulfonyl)imides.
AB  - The alpha,alpha'-stabilized carbanion complexes [(PhSO2)2CHLi.THF]1,
      [(PhSO2)2CHNa.THF]2 and [(PhSO2)2CHK]3 were prepared by the direct deprotonation
      of bis(phenylsulfonyl)methane I in THF with one molar equivalent of MeLi, BuNa
      and BnK respectively. The geminal dianionic complexes [(PhSO2)2CLi2.THF]4,
      [(PhSO2)2CNa2.0.55THF]5 and [(PhSO2)2CK2]6 were similarly prepared by the
      reaction of I with two molar equivalents of MeLi, BuNa and BnK respectively in
      THF. NMR and MS solution studies of 1-3 are consistent with the formation of
      charge-separated species in DMSO media. Solutions studies of 4-6, in conjunction
      with trapping experiments, indicate that the dianions deprotonate DMSO and
      regenerate the monoanions 1-3. Crystallographic analysis of 1 revealed a 1D chain
      polymer in which the metal centers are chelated by the bis(sulfonyl) ligands and
      connect to neighboring units through Li-O(S) interactions. An unexpected feature
      of 1 is that the polymeric chains are homochiral, since the chelating ligands of
      the backbone adopt the same relative configuration. Also, the phenyl substituents
      of each chelate in 1 are oriented in a cisoid manner. The sodium derivative 2
      adopts a related solid-state structure, where enantiomeric pairs of chains
      combine to give a 1D ribbon motif. The lithium bis(phenylsulfonyl)imides
      [(PhSO2)2NLi.THF]9 and [(PhSO2)2NLi.Pyr2]10 were also prepared and structurally
      characterized. In the solid state 9 has a similar connectivity to that found for
      1 but with heterochiral chains. In comparison, the more highly solvated complex
      10 forms a 1D polymeric arrangement without chelation of the ligands and with the
      phenyl substituents oriented in a transoid fashion.

PMID- 15957048
TI  - Pt(II) mono-carbonyl complexes of a cyclometallating 2-(2'-thienyl)-(pyridinato
      C,3N') ligand: nature and dynamics of the lowest excited state of the chloro- and
      thiolato-complexes.
AB  - The synthesis of a cyclometallated Pt(II) thiolate carbonyl complex
      Pt(thpy)(CO)(mts), (thpy = 2-(2'-thienyl)-pyridinate, mts = methylthiosalicylate)
      is reported. A combination of emission and time-resolved infrared (TRIR)
      techniques revealed for both Pt(thpy)(CO)(mts) and its chloride analogue
      Pt(thpy)(CO)Cl the predominant intra 2-(2'-thienyl)-pyridinate 3pi pi* character
      of the lowest electronic excited state. The unusually short lifetime (780 ps) of
      the intraligand 3pi pi* lowest excited state of Pt(thpy)(CO)(mts) indicates that
      this electronic state is influenced by another close-lying excited state,
      probably charge-transfer in origin.

PMID- 15957049
TI  - A systematic investigation of aluminium ion speciation at high temperature. Part
      1. Solution studies.
AB  - Speciation diagrams of aluminium ions in aqueous solution (0.2 M) at high
      temperature (90 degrees C) have been obtained from 48 h time-resolved multi-batch
      titration experiments monitored by 27Al NMR spectroscopy, potentiometry and
      dynamic light scattering. The quantitative speciation patterns and kinetic data
      obtained offer a dynamic picture of the distribution of soluble and insoluble Al
      species as a function of hydrolysis ratio h(h=[OH-]/[Al3+]) over a very broad
      range of conditions (-1.0 < or =h < or = 4.0). Monomeric, small oligomeric,
      tridecameric (the 'Al13-mer') and the recently characterised 30-meric aluminium
      species (the 'Al30-mer') as well as aluminium hydroxide have been identified and
      quantified. The Al13-mer species dominates over a relatively broad range of
      hydrolysis ratios (1.5 < or =h< or = 2.7) during the first 6 h of experiment, but
      are gradually replaced by Al30-mers at longer reaction times. Kinetic profiles
      indicate that the formation of the Al30-mer is limited by the disappearance of
      the Al13 species at mildly acidic conditions. The estimated rate constants of
      both hydrolytic processes show good internal correlation at h> or = 1.5. The
      effect of local perturbations leading to the formation of aluminium hydroxide
      below the electroneutrality point (h= 3.0) has been estimated quantitatively.

PMID- 15957050
TI  - Oxidation reactions of an anionic gallium(I) N-heterocyclic carbene analogue with
      group 16 compounds.
AB  - The reactivity of an anionic gallium(I) heterocycle,
      [K(tmeda)][:Ga([N(Ar)C(H)]2)], Ar = C6H3Pr(i)2-2,6, towards sources of elemental
      chalcogens and diorgano-dichalcogenides has been investigated and comparisons
      drawn with the reactivity of the valence isoelectronic N-heterocyclic carbene
      class of ligand. The reactions of the heterocycle with N2O or (Te)PEt3 yielded
      the dimeric, dianionic gallium(III) complexes, [K(L)]2[(mu-E)Ga([N(Ar)C(H)]2)]2,
      E = O, L = tmeda; E = Te, L = THF. Treatment of [K(tmeda)][:Ga([N(Ar)C(H)]2)]
      with the diphenyl dichalcogenides, PhEEPh, E = Se or Te, gave the one dimensional
      polymer, [K[(PhSe)2Ga([N(Ar)C(H)]2)]]infinity and the monomeric complex,
      [K(OEt2)3][(PhTe)2Ga([N(Ar)C(H)]2)], respectively. The X-ray crystal structures
      of the four complexes are reported.

PMID- 15957051
TI  - Templated metal-organic frameworks: synthesis, structures, thermal properties and
      solid-state transformation of two novel calcium-adipate frameworks.
AB  - Two novel calcium-adipate framework materials have been synthesized
      hydrothermally. GWMOF-7 ([Ca(C6H8O4)(H2O)2]*(C10H8N2)) and GWMOF-8
      ([Ca(C6H8O4)(H2O)2]*(C12H12N2)) both formed three-dimensional structures and were
      characterized with single-crystal X-ray diffraction, powder X-ray diffraction, IR
      spectroscopy and elemental analysis. Thermal properties were also studied with
      thermogravimetric analysis, and show that these structures undergo a solid-state
      transformation into a denser three-dimensional framework.

PMID- 15957052
TI  - Amido-bridged double-cube nitrido complexes containing titanium and
      magnesium/calcium.
AB  - Treatment of the single cube nitrido complexes [(thf)x((Me3Si)2N)M((mu3-N)(mu3
      NH)2Ti3(eta5-C5Me5)3(mu3-N))](M = Mg, x= 0; Ca, x= 1) with one equivalent of
      anilines NH2Ar in toluene affords the arylamido complexes [(ArHN)M((mu3-N)(mu3
      NH)2Ti3(eta5-C5Me5)3(mu3-N))]n[M = Mg (3), n= 1, Ar = 4-MeC6H4; Ca (4), n= 2, Ar
      = 2,4,6-Me3C6H2]. The magnesium complex 3 has a single-cube structure whereas the
      X-ray crystal structure of the analogous calcium derivative 4 shows two cube-type
      azaheterometallocubane moieties Ca((mu3-N)(mu3-NH)2Ti3(eta5-C5Me5)3(mu3-N)) held
      together by two mu-2,4,6-trimethylanilido ligands. Complexes 3 and 4 react with
      chloroform-d1 at room temperature to give the metal halide adducts [Cl2M((mu3
      NH)3Ti3(eta5-C5Me5)3(mu3-N))](M = Mg, Ca). A solution of 3 in n-hexane gave
      complex [(Mg2(mu3-N)(mu3-NH)5[Ti3(eta5-C5Me5)3(mu3-N)]2)(mu-NHAr)3] which shows
      three mu-4-methylanilido ligands bridging two [MgTi3N4] cube type cores according
      to an X-ray crystal structure determination.

PMID- 15957053
TI  - Cyano-bridged gadolinium(III)-tungstate(V) bimetallic assembly with a one
      dimensional chain structure.
AB  - In this paper, we report the crystal structure and magnetic properties of the
      cyano-bridged gadolinium-tungstate bimetallic assembly, GdIII(DMF)6[WV(CN)8](DMF
      =N,N-dimethylformamide). X-Ray single crystal analysis shows that this compound
      crystallizes in the monoclinic system of space group P2(1)/c with cell constants
      a= 16.40(2)A, b= 11.08(1)A, c= 21.18(2)A, beta= 91.09(8) degrees, and Z= 4. The
      crystal consists of one-dimensional linear chains, in which [GdIII(DMF)6]3+ and
      [WV(CN)8]3- ions are linked in an alternating fashion. The magnetic data show
      that this compound is a paramagnet with an antiferromagnetic coupling of -0.58 cm
      1 between GdIII(S= 7/2) and WV(S= 1/2).

PMID- 15957054
TI  - Rhenium oxo compounds containing eta2-pyrazolate ligands.
AB  - Reaction of potassium salts of sterically demanding pyrazolates (pz = bis-3,5
      tert-butylpyrazolate, pz= bis-3,5-tert-butyl-4-methylpyrazolate) with Re2O7
      affords soluble eta2-pyrazolate complexes of the type [(eta2-pz)ReO3(THF)n](1:
      pz, n= 1 and 2: pz, n= 0). They were characterized by spectroscopic methods and
      by X-ray crystallography confirming the eta2-coordinate ligands. Complex 1
      employing the ligand with a proton in the 4-position retains one molecule of THF,
      whereas the additional methyl group in 2 leads to the base-free compound 2.
      Compound 1 reacts with pyridine and 3,5-dimethylpyridine to form Lewis base
      adducts of the type [(eta2-pz)ReO3(L)](3: L = py; 4: L = 3,5-Me2py). The
      pronounced sensitivity towards water of these complexes is demonstrated by the
      reaction of 1 with one equivalent of water forming the corresponding pyrazolium
      perrhenate [ReO4][pzH2](5). Its solid state structure shows a hydrogen bonded
      dimeric assembly. Catalytic activity of 1 is established in oxygen atom transfer
      reactions (OAT) from dimethylsulfoxide to triphenylphosphine, and in epoxidations
      of cyclooctene employing bis(trimethylsilyl) peroxide (BTSP).

PMID- 15957055
TI  - Selective oxygenation of amphiphilic thiacalix[3]pyridine Rh(I) diene complexes
      in both water and organic solvents.
AB  - Thiacalix[3]pyridine (Py3S3) reacted with [Rh(diene)(mu-Cl)]2(diene = 1,5
      cyclooctadiene (cod), 2,5-norbornadiene (nbd)) to give amphiphilic trigonal
      bipyramidal complexes, [Rh(Py3S3)(diene)]Cl. Sulfur bridges of the Py3S3 ligand
      in these complexes were selectively oxygenated by m-chloroperoxybenzoic acid in
      dichloromethane to give sulfinylcalix[3]pyridine complexes,
      [Rh(Py3(SO)3)(diene)]+, in which all three oxygen atoms of the SO groups occupy
      the equatorial positions. Structures of the complexes were analysed by X-ray
      crystallography and the oxidation reaction was investigated using 1H NMR
      spectroscopy and electrospray ionisation mass spectrometry showing that the
      oxygenation of the sulfur atoms in the ligand proceeded stepwise and further
      oxygenation of the SO moiety occurred only for the nbd complex having the smaller
      diene ligand resulting in [Rh(Py3(SO)2(SO2))(nbd)]+. On the other hand, the
      oxidation of [Rh(Py3S3)(cod)]+ by H2O2 in water did not result in oxygenation of
      the sulfur bridges but the cod ligand is hydroxygenated to give 1,4,5,6-eta4-2
      hydroxycycloocta-4-ene-1,6-di-yl.

PMID- 15957056
TI  - Kinetics and mechanism of the stepwise complex formation of Cu(II) with tren
      centered tris-macrocycles.
AB  - The stepwise complexation kinetics of Cu2+ with three tetratopic ligands L1, L2
      and L3, tren-centred macrocycles with different bridges connecting the 14
      membered macrocycles with the tren unit, have been measured by stopped-flow
      photodiode array techniques at 25 degrees C, I= 0.5 M (KNO3), and pH = 4.96. The
      reaction between the first Cu2+ and the ligand consists of several steps. In a
      rapid reaction Cu2+ first binds to the flexible and more reactive tren-unit. In
      this intermediate a translocation from the tren unit to the macrocyclic ring,
      which forms the thermodynamic more stable complex, takes place. This species can
      react further with a second Cu2+ to give a heterotopic dinuclear species with one
      Cu2+ bound by the tren-unit and the other coordinated by the macrocycle. A
      further translocation occurs to give the homoditopic species with two Cu2+ in the
      macrocycles. Finally a slow rearrangement of the dinuclear complex gives the
      final species. The rates of the translocation are dependent on the length and
      rigidity of the bridge, whereas the complexation rates with the tren unit are
      little affected by it. VIS spectra of the species obtained by fitting the kinetic
      results, EPR-spectra taken during the reaction, and ES mass spectra of the
      products confirm the proposed mechanism. The addition of a second, third and
      fourth equivalent of Cu2+ proceeds in an analogous way, but is complicated by the
      fact that we start and end with a mixture of species. These steps were evaluated
      in a qualitative way only.

PMID- 15957058
TI  - Synthesis, structure and catalytic activity of thioether-phosphane complexes of
      Pd(II) and Pt(II).
AB  - New thioether-phosphanes 2-RSC6H4CH2PPh2(RS-PPh2: R = Me, tBu, Ph) and the
      corresponding complexes [PdCl2(MeS-PPh2)], [PdCl2(tBuS-PPh2)], [PdCl2(PhS-PPh2)],
      [PdClMe(MeS-PPh2)] and [PtMe2(MeS-PPh2)] have been prepared, characterized and
      the X-ray crystal structures of all complexes determined. Whilst Pd(II) complexes
      of RS-PPh2 show low activity for CO/ethene copolymerisation, the complexes
      [PdCl2(RS-PPh2)] have been found to be very efficient for the Heck arylation of n
      butylacrylate with bromobenzene under aerobic conditions.

PMID- 15957057
TI  - Zirconium complexes having a chiral phosphanylamide in the co-ordination sphere.
AB  - The chiral phosphanylamido ligand, (N(CHMePh)(PPh2))-, has been introduced into
      co-ordination chemistry. As starting material the oily amines HN(R
      *CHMePh)(PPh2)(1a) and HN(S-*CHMePh)(PPh2)(1b) were used. To reconfirm their
      absolute structure, 1b was oxidized with H2O2 in air to obtain HN(S
      *CHMePh)(P(O)Ph2)(2) as a solid compound. The solid-state structure of 2 was
      established by single-crystal X-ray diffraction. The lithium salts of both
      enantiomers Li(N(R-*CHMePh)(PPh2))(3a) and Li(N(S-*CHMePh)(PPh2))(3b) were
      prepared by deprotonation reaction of 1a,b. Compounds 3a,b were further reacted
      with zirconocen dichloride to give the chiral metallocenes [(eta5
      C5H5)2Zr(Cl)(eta2-N(R-*CHMePh)(PPh2))](4a) and [(eta5-C5H5)2Zr(Cl)(eta2-N(S
      *CHMePh)(PPh2))](4b). In an alternative approach to give chiral zirconium
      compounds, the neutral amine 1b was reacted with [(PhCH2)4Zr] to give the
      enantiomeric pure complex [(PhCH2)3Zr(eta2-N(S-*CHMePh)(PPh2))](5). The solid
      state structures of all zirconium complexes were determined by single-crystal X
      ray diffraction.

PMID- 15957059
TI  - Reactions of halogens with Pt(II) complexes of N-alkyl- and N,N-dialkyl-N'
      benzoylthioureas: oxidative addition and formation of an I2 inclusion compound.
AB  - The treatment of cis-[Pt(II)(L(1a/b)-S,O)2] complexes of N,N-diethyl- (HL(1a))
      and N,N-di(n-butyl)-N'-benzoylthiourea (HL(1b)) with I2 or Br2 in chloroform,
      leads to rapid oxidative addition to yield several geometric isomers of [Pt(IV)(L
      S,O)(2)X(2)](X = I, Br); the reactions can be monitored by (195)Pt NMR and UV
      visible spectrophotometry. The products cis-[Pt(IV)(L(1a)-S,O)2I2] and cis
      [Pt(IV)(L(1a)-S,O)2Br2], which have been isolated and structurally characterized,
      are the first-reported crystal structures of complexes of Pt(iv) with this class
      of ligand. Molecules of 6 pack such that the I-Pt-I axes are essentially aligned,
      with unusually close nearest-neighbour iodide contacts (3.553(1)A). These short
      II intermolecular interactions lead to infinite chains of weakly connected
      molecules in crystals of the compound. No such interactions are evident in the
      corresponding crystals of . Reaction of the Pt(II) complex of N-propyl-N'
      benzoylthiourea (H2L(2a))cis-/trans-[Pt(II)(H2L(2a)-S)2Br2] with Br2 also results
      in oxidative addition, to yield trans-Pt(IV)(H2L(2a)-S)2Br4. By contrast,
      treatment of cis-/trans-[Pt(II)(H2L(2a)-S)2I2] with I2 does not lead to an
      oxidative addition product, yielding instead an interesting iodine inclusion
      compound of Pt(II), trans-[Pt(II)(H2L(2a)-S)2I2.I2. In 8, short intermolecular II
      distances of 3.453(1)A between I2 and coordinated iodide ions in trans
      [Pt(II)(H(2)L(2a)-S)(2)I(2)] molecules, result in infinite chains of weakly
      linked trans-[Pt(II)(H2L(2a)-S)2I2]...I2 groups in the lattice. However, the
      empirically estimated bond order of 0.75 for the included I2 molecules does not
      support the possible existence of discrete tetraiodide ions (I4(2-)) in the
      lattice of compound 8.

PMID- 15957060
TI  - Synthesis, structure and dynamics of methoxynaphthalene-substituted phospha
      ruthenocenes and -ferrocenes.
AB  - The syntheses of potassium 2-(2'-methoxynaphth-1'-yl)-3,4-dimethyl-5
      phenylphospholide 4 and eta5-pentamethylcyclopentadienyl(eta5-2-(2-methoxynaphth
      1-yl)-3,4-dimethyl-5-phenylphospholyl)-ruthenium(II)5 and -iron(II)6 are
      described. The barrier to rotation of the naphthyl group (79 kJ mol-1 and 72 kJ
      mol-1 in CD2Cl2 respectively) characterises 5 and 6 as potential tropos type
      ligands. Coordination of 5 to [PtCl2(PEt3)] gives two cis and two trans complexes
      [PtCl2(PEt3)5] wherein rotation about the phospholyl-naphthyl vector is slow.

PMID- 15957061
TI  - Syntheses and reactions of the bis-boryloxide O(Bpin)2(pin = O2C2Me4).
AB  - The reaction of the phosphine oxides, OPEt31 and OPn-Bu32 with pinacolborane
      (HBpin) results in phosphine oxide reduction and the formation of O(Bpin)23. In
      contrast, the phosphine oxide OPn-Bu3 reacts with HB(C6F5)2 or B(C6F5)3 to give
      only the donor-acceptor adducts. Compound 3 reacts with HNPt-Bu3 to give the
      phosphinimonium borate salt, [t-Bu3PNH2][(Bpin(OBpin)2]6, while reaction with
      Cp2ZrMe2 affords the species Cp2Zr(OBpin)27.

PMID- 15957063
TI  - Discovery of protein drugs from natural sources.

PMID- 15957062
TI  - Synthesis and structure of novel [Ph(RO)PSe2]- complexes.
AB  - Reaction of (PhPSe2)2(Woollins reagent) with NaOR (R = Me, Et, (i)Pr) gives the
      non-symmetric phosphonodiselenoato anions [Ph(RO)PSe2]- which can be complexed to
      a range of metals. The nickel complex Ni[Ph(MeO)PSe2]2 adopts a square-planar ML2
      structure while the cadmium complex Cd[Ph(MeO)PSe2]2 displays a dimeric M2L4
      structure. Two different lead complexes are observed, one consisting of PbL2
      units joined by Pb...Se interactions to form distinct dimeric pairs. The other
      displays a novel dimeric structure built around a central four-membered Pb2Se2
      ring. All new compounds have been characterised spectroscopically (31P, 1H, 13C
      NMR, IR, mass spectroscopy), by elemental analysis and five demonstrative X-ray
      structures are reported.

PMID- 15957064
TI  - American Chemical Society-222nd national meeting.

PMID- 15957066
TI  - American Chemical Society--222nd national meeting. Cannabinoids: a tale of use
      and abuse.

PMID- 15957065
TI  - American Chemical Society--222nd national meeting. Symposium highlights.

PMID- 15957067
TI  - American Chemical Society--222nd national meeting. Highlights from the oral
      sessions.

PMID- 15957068
TI  - American Chemical Society--222nd national meeting. Highlights from the poster
      sessions.

PMID- 15957069
TI  - American Chemical Society--222nd national meeting. Proteasome symposium.

PMID- 15957070
TI  - American Chemical Society--222nd national meeting. Growth hormone secretagogues.

PMID- 15957071
TI  - American Chemical Society--222nd national meeting. NPY antagonists and non-taxoid
      antitubule inhibitors.

PMID- 15957072
TI  - American Chemical Society--222nd national meeting. Division of computers in
      chemistry.

PMID- 15957073
TI  - RSC-SCI medicinal chemistry--11th symposium.

PMID- 15957074
TI  - RSC-SCI medicinal chemistry--11th symposium. Highlights from the poster
      presentations.

PMID- 15957075
TI  - RSC-SCI medicinal chemistry--11th symposium. New technologies and late-breaking
      science.

PMID- 15957076
TI  - RSC-SCI medicinal chemistry--11th symposium. Receptors and ion channels.

PMID- 15957077
TI  - European Association of Clinical Pharmacology and Therapeutics--Fifth Congress.
      Clinical pharmacology: from molecule to society--bridging the gap via Man.

PMID- 15957078
TI  - British Pharmacological Society/The Physiological Society--joint meeting.
      Advances in glutamatergic pharmacology.
AB  - As befits the coming together of two major national societies, the Bristol
      meeting attracted a significant array of eminent pharmacologists and
      physiologists. This was reflected in the presentation of over 350 poster and oral
      communications stretching over the 3 days, with the host institution contributing
      substantially to the proceedings. A significant number of communications relating
      to glutamatergic transmission were presented, which will be the focus of this
      review. New information was disclosed relating to a novel class of metabotropic
      glutamate receptor modulators, recent advances in Glu(K5) compounds, AMPA/kainate
      and AMPA/NMDA receptor discriminators, and NMDA receptor subtype-selective
      compounds. Disclosures pertain to therapeutic areas including epilepsy,
      Parkinson's disease, cognitive enhancement, analgesia and psychosis.

PMID- 15957079
TI  - AIDS vaccine 2001.
AB  - It has been reported that 5.4 million new HIV infections occur each year, 10% of
      which are in children and 50% in females. Over 90% of infections occur in the
      developing world where highly active antiretroviral therapy is unlikely to be
      readily available. Therefore, the need for a prophylactic vaccine for HIV is
      compelling. All sessions of 'AIDS Vaccine 2001' were valuable, but this report
      mainly considers two slide sessions where new candidate vaccines and vaccine
      strategies were discussed. It is of major importance that as many novel vaccine
      strategies as possible are explored, and that meaningful comparisons are made
      between the responses they induce. Even a vaccine that does not offer full
      sterilizing immunity to HIV infection could have a dramatic effect on the
      pathogenesis of HIV disease and on transmission of HIV from person to person.

PMID- 15957081
TI  - European Society of Cardiology--XXIII congress.

PMID- 15957080
TI  - AIDS Vaccine 2001. Advances in AIDS research.

PMID- 15957082
TI  - European Society of Cardiology--XXIII congress. New and established therapies.
AB  - The annual European Society of Cardiology XXIII Congress was an internationally
      represented meeting, focusing on the latest developments in cardiac
      pharmaceutical research and clinical applications. Poster and oral presentations
      displayed the importance of clinical trials for safety and efficacy of current
      drugs mainly acting on blocking of signaling pathways in the hyperactivated
      failing heart or prevention and reversion of vessel occlusions. Additionally,
      several new drug classes were introduced and tested in small-scale studies. In
      addition to improved surgical methods discussed at the congress, new classes of
      minimally invasive treatments were reported, including gene therapy and cell
      transplantation techniques which could provide additional future cure for cardiac
      patients.

PMID- 15957083
TI  - Gene therapy and molecular biology--international conference 2001.

PMID- 15957084
TI  - Hungarian-German-Italian-Polish joint meeting on medicinal chemistry.
AB  - The Hungarian-German-Italian-Polish Joint Meeting on Medicinal Chemistry, an
      internationally represented meeting of medicinal chemists, took place in the
      historic castle district of Budapest. Two previous joint meetings have been held
      in Italy and Poland. The main topics included significant challenges facing
      today's medicinal chemist. This report highlights novel results discussed at the
      meeting.

PMID- 15957085
TI  - Non-toxic immunogens for therapeutic anticytokine vaccines.
AB  - Over the last decade, the availability of purified cytokines and of cytokine
      antibodies (Abs) has prompted both scientists and pharmaceutical companies to
      develop anticytokine Ab therapy, and clinical trials have shown that anticytokine
      Abs are transiently effective. Active immunization may offer advantages over
      passive immunization in many situations. As anticipated from basic research,
      preclinical experiments and recent trials, such vaccines are safe and elicit high
      neutralizing anti-Ab titers. Repeated booster injections at 4 +/- 2 month
      intervals are however necessary to maintain long-term, high-affinity Ab response
      and efficacy. Anticytokine vaccines, alone or in combination with other
      therapies, represent potential treatments for chronic diseases such as AIDS,
      cancer, allergy and autoimmunity.

PMID- 15957086
TI  - Schizophrenia: etiology and pharmacotherapy.
AB  - Schizophrenia is one of the major psychiatric disorders. Psychosis, in its narrow
      definition, is restricted to delusions or hallucinations in the absence of
      insight into their pathological nature. Impairment in psychosocial function is an
      essential feature of schizophrenia. Research in the last decade has confirmed
      that schizophrenia is a brain disorder that cannot be attributed solely to
      psychosocial factors. It is widely accepted from twin and adoption studies that
      schizophrenia has a significant genetic component. In addition, it is a general
      belief that schizophrenia is caused by a biological abnormality, even though all
      attempts to identify that abnormality have been unsuccessful. A major landmark in
      the history of the understanding and treatment of schizophrenia was the discovery
      that dopamine D2-blocking agents can control the hallucinations and delusions of
      schizophrenic patients. However, clinicians have noticed that classical
      antipsychotics are generally ineffective against the negative symptoms that are
      prominent in patients with a chronic course. In this article, we will focus on
      the etiology and pharmacotherapy of schizophrenia.

PMID- 15957087
TI  - Lp-PLA2 inhibitors (GlaxoSmithKline).
AB  - GlaxoSmithKline is investigating a series of substituted pyrimidin-4-ones,
      including SB-435495, as reversible inhibitors of lipoprotein-associated
      phospholipase A(2) (Lp-PLA(2)) for the potential treatment of atherosclerosis
      [339220], [422380]. This series is being developed alongside a series of
      irreversible inhibitors such as SB-222657 and derivatives of SB-253514 [339220],
      [401355]. SB-435495 was discovered through the use of gene technology provided by
      Human Genome Sciences (HGS) [400047]. By October 2001, phase II trials of SB
      435495 had been initiated [424613].

PMID- 15957088
TI  - CTC-11 (Teijin).
AB  - Teijin and Chemo-Sero are codeveloping CTC-111 as a treatment for disseminated
      intravascular coagulation (DIC) due to protein C deficiency. The drug was
      launched for the treatment of protein C deficiency in Japan on January 31, 2001
      and as of October 2001 was awaiting approval for the treatment of DIC, also in
      Japan [426762]. CTC-111 was evaluated in a multicenter pharmacokinetic trial in
      venous thrombosis patients with inherited protein C deficiency. CTC-111 was
      effective in six of ten patients with venous thrombosis, six of seven patients
      with deep vein thrombosis and two of three patients with pulmonary embolism.
      Treatment was safe and effective and there were no serious adverse events
      [350149].

PMID- 15957089
TI  - Figures, tables, and references: integral but sometimes neglected components of
      scientific articles.

PMID- 15957090
TI  - Publication rates of scientific presentations in Turkish national radiology
      congresses.
AB  - PURPOSE: To investigate the publication rates of scientific presentations in
      Turkish radiology congresses. MATERIALS AND METHODS: The abstracts of
      presentations at Turkish national radiology congresses between 1995-2002 were
      reviewed. According to the congress abstract booklets, types of the presentation
      (oral or poster presentation), as well as body system-based categorization were
      used. The presentations were searched for publication in Medline(R) indexed
      journals using the PubMed server. The rates of publication of the abstracts, the
      journals in which the presentations have been published and the time between the
      presentation and publication were investigated. RESULTS: An overall number of 521
      publications were found originating from 4,413 presentations (11.81%). The
      publication numbers of 2,116 scientific research, 1,995 case report and 302
      educational exhibit type presentations were 261 (12.33%), 249 (12.49%) and 11
      (3.64%), respectively. For oral presentations the publication ratio was found as
      15.38% (116/754) and for posters it was 11.06% (405/3,659). The number of
      presentations and the number of publications were found to increase by years,
      however the ratio of publication to presentation remained the same. Mean time to
      publication was calculated as 24.4 months. In frequency of publication, Tanisal
      ve Girisimsel Radyoloji, European Radiology, European Journal of Radiology were
      the first three publication media of the presentations. CONCLUSION: The
      publication rates of abstracts presented at Turkish national radiology congresses
      are lower than the previously reported publication rates in radiology and other
      specialties.

PMID- 15957091
TI  - Correlation between the adverse reactions to intravenous iodinated contrast media
      and IgE levels.
AB  - PURPOSE: The adverse reactions of the iodinated contrast media are believed to be
      non-IgE mediated and the result of triggering of the release of the mast cell
      mediators directly. However, the exact mechanism is still controversial and
      purpose of this prospective study is not only to determine any possible
      correlation of adverse reactions with total baseline blood IgE levels, but also
      to investigate the change of the IgE levels in the blood after the administration
      of the IV iodinated contrast media and correlate this with the various side
      effects. MATERIALS AND METHODS: Blood samples were taken from 110 patients who
      underwent excretory urography just before the administration of the iodinated
      contrast media and on the 40th minute. Further blood samples were collected from
      13 randomly selected patients out of the total 110, a week after the
      examinations. Total IgE levels were calculated in all samples using
      electrochemiluminescense immunoassay method. RESULTS: IgE levels decreased
      statistically significantly using paired t test in all patients but one. The side
      effects were independent from the total baseline IgE levels according to the chi
      square testing. CONCLUSION: Results reveal that the measurement of the total
      baseline IgE levels can not be a prognostic factor for the adverse reactions to
      iodinated contrast media but the more a factor causes immuneglobuline to decrease
      after administration of iodinated contrast media, the less adverse reactions
      happen. Electrochemiluminescense immunoassay method ought to be scrutinized for
      the detection of IgE binded with iodinated contrast media.

PMID- 15957092
TI  - Spiral CT angiography in diagnosis of cerebral aneurysms of cases with acute
      subarachnoid hemorrhage.
AB  - PURPOSE: To investigate the diagnostic accuracy of spiral CT angiography (CTA) in
      detection of cerebral aneurysms in cases with acute subarachnoid hemorrhage
      (SAH). MATERIALS AND METHODS: Spiral CT angiography and DSA examinations were
      performed in 32 cases due to non-traumatic SAH. CTA data were obtained by maximum
      intensity projection (MIP) method. CTA and DSA findings were evaluated and
      compared in terms of existence of aneurysm, size and location. RESULTS: In 32
      patients, DSA detected 34 aneurysms with diameters ranging from 3 to 13 mm while
      four cases were free of aneurysms. With CTA, an aneurysm at anterior
      communicating artery location could not be demonstrated. In all other cases CTA
      correlated well with DSA in detecting the site, size and orientation of the
      aneurysms. It was found that CTA sensitivity was 97% and specificity was 100% in
      diagnosis of intracranial aneurysms. CONCLUSION: Spiral CTA is a highly accurate,
      cheap and non-invasive imaging method in diagnosis of intracranial aneurysms in
      cases with SAH and can be used as a safe alternative method to DSA when emergency
      surgery is needed.

PMID- 15957093
TI  - Primary cerebellar glioblastoma multiforme.
AB  - Primary glioblastoma multiforme of cerebellar hemispheres in adults is a rare
      condition. Most of them result from dedifferentiation of astrocytoma to
      glioblastoma. We present two cases of unusual de novo cerebellar glioblastomas,
      one of which is the giant-cell variant. We review their clinical behaviour with
      conventional MR imaging features and discuss the key findings that can lead to
      the correct diagnosis in sight of new MR imaging technologies.

PMID- 15957094
TI  - MR imaging and ultrasound of fetal cervical cystic lymphangioma: utility in
      antepartum treatment planning.
AB  - We present a case of fetal cystic lymphangioma that was initially diagnosed by
      ultrasonography and further evaluated by prenatal MR imaging. MR imaging findings
      aided in improved delineation of the neck mass. T2-weighted MR images revealed
      partial compression of the airway by the neck mass. This information was useful
      in the decision to use ex utero intrapartum treatment (EXIT) and helped surgeons
      in planning their approach to establish airway control during delivery.

PMID- 15957095
TI  - Superior mesenteric artery syndrome: CT and ultrasonography findings.
AB  - PURPOSE: The purpose of the study was to describe computed tomography (CT) and
      ultrasonography findings in superior mesenteric artery syndrome (SMAS). MATERIALS
      AND METHODS: The study was performed on 89 CT examinations. Ultrasonography was
      performed on 32 and barium study was performed on four of these subjects. Group A
      consisted of cases with one or more of the following complaints: postprandial
      epigastric pain, weight loss and vomiting. Group B consisted of the remaining
      cases. Cases who had all of the above-mentioned clinical findings and duodenal
      dilatation, to-and-fro barium movement and SMA indentation in barium study were
      diagnosed as having SMAS. Body mass index (BMI, kg/m2) was calculated. The
      distance between SMA and aorta, at the location where the duodenum passes from,
      was measured on CT and ultrasonography. The angle between SMA and aorta was
      measured on ultrasonography images. Group and gender differences were analyzed
      with t-test, the relationship between clinical and CT findings was analyzed with
      Mann Whitney U test and the relations between BMI-CT and CT-ultrasonography
      measurements were analyzed with Pearson coefficients. RESULTS: Of 13 cases in
      Group A, 3 were diagnosed as SMAS. Eight of the cases showed gastric and/or
      duodenal dilatation. In 6 cases, antrum had an abnormally high location at portal
      hilus. In Group A, the SMA-aorta distance was 6.6 +/- 1.5 mm and the SMA-aorta
      angle was 18.7 +/- 10.7 degrees . In Group B, these values were 16.0 +/- 5.6 mm
      and 50.9 +/- 25.4 degrees , respectively (p < 0.001). Cut-off values between SMAS
      and Group B were 8 mm (100% sensitivity and specificity), and 22 degrees (42.8%
      sensitivity, 100 % specificity). CT and ultrasonography measurements (p < 0.001)
      and SMA-aorta distance and BMI (p=0.004) were significantly correlated. The SMA
      aorta distance was significantly shorter in females (p=0.036). CONCLUSION:
      Gastric and/or duodenal dilatation and a diminished SMA-aorta distance have a
      significant correlation with clinical symptoms of SMAS that include postprandial
      pain, vomiting and weight loss.

PMID- 15957096
TI  - Transient hepatic attenuation differences at biphasic spiral CT examinations.
AB  - Transient hepatic attenuation difference (THAD) is a perfusion disorder that can
      sometimes be observed in hepatic arterial phase of a biphasic spiral CT
      examination. The involved site of liver by THAD appears as an area of high
      attenuation on the hepatic arterial phase image and returns to normal attenuation
      on portal venous phase image. The knowledge of the shape, distribution and causes
      of THAD is essential to differentiate the THAD from other pathologies such as
      neoplasm.

PMID- 15957097
TI  - Gastric stromal tumor.
AB  - Gastric stromal tumors are rare neoplasms of the stomach. In this report we
      present a gastric stromal tumor with an exophytic growth pattern, and describe
      magnetic resonance imaging and endoscopic ultrasonography findings.

PMID- 15957098
TI  - Automated measurement of intima-media thickness of carotid arteries in
      ultrasonography by computer software.
AB  - PURPOSE: Intima-media thickness (IMT) has been proposed to be a morphological
      criterion of atherosclerosis. The purpose of this study was to investigate the
      interobserver variability of manual and also of computer software measurements of
      IMT. MATERIALS AND METHODS: High-resolution common carotid artery (CCA) images of
      88 patients that have been obtained by a linear broadband L5-12 MHz transducer
      and archived in PACS were retrospectively evaluated. Two separate investigators,
      who were unaware of the former results, evaluated the same images by using
      computer software that had a dedicated tool for automatic measurement of IMT. The
      results of the investigators were compared. RESULTS: According to the two
      investigators who have performed manual measurements, mean values of IMT of right
      CCA were 0.6396 mm and 0.6356 mm; of the left CCA were 0.6662 mm and 0.6575 mm,
      respectively. The interobserver variability of measurements revealed the mean IMT
      as 0.6071 mm and 0.6048 mm for the right, 0.6216 mm and 0.6227 mm for the left
      CCA. Manual measurements of both investigators were found to be higher than the
      automatic measurements and the differences were statistically significant.
      Interobserver correlation of manual measurements was between 0.80-0.88 and of the
      automated measurements was between 0.93-0.98. CONCLUSION: Manual measurements
      reveal higher values than the automated measurements of IMT. The interobserver
      correlation of automated measurements is higher than manual measurements. The use
      of dedicated software may be proposed to reduce the measurement errors.

PMID- 15957099
TI  - Adverse effects of anesthesia in interventional radiology.
AB  - PURPOSE: The aim of the study was to evaluate adverse events related to the use
      of anesthesia and anesthetic procedures associated with interventional radiology.
      MATERIALS AND METHODS: We retrospectively evaluated 124 interventional
      radiological procedures performed with anesthesia within a one-year period.
      Patients were separated into four groups according to the duration of procedure,
      the type of procedure performed, anesthetic agents used, and complications
      associated with anesthesia. RESULTS: Of the 124 patients, 59 had neurovascular
      procedures, 10 underwent implantation of a tracheal stent, and 19 had painful
      procedures. Fifteen of 36 pediatric patients had diagnostic angiography, and 21
      had interventional procedures. Two patients in the neurovascular intervention
      group had cerebral hemorrhage and cerebral infarctions, and anaphylactic reaction
      developed in one patient, who underwent percutaneous hepatic hydatic cyst
      drainage. CONCLUSION: Interventional radiological procedures seem to be safe from
      an anesthesiologist's point of view. However, morbidity and mortality in this
      patient population can be reduced when the potential complications associated
      with interventional radiology are well understood by the anesthesia team.

PMID- 15957100
TI  - Gene therapy: applications in interventional radiology.
AB  - Gene therapy is a new and rapidly developing area in medicine. Although it is a
      new therapy method, recent studies look promising. Since vascular wall is a good
      target for this treatment, interventional radiologists should become familiar
      with this new therapy and be involved in this multidisciplinary collaboration.

PMID- 15957101
TI  - Endovascular stent graft treatment in a patient with splenic artery aneurysm.
AB  - Splenic artery aneurysms are rare but important vascular lesions that constitute
      approximately 60% of all visceral arterial aneurysms. Splenic artery is the third
      most common localization of intraabdominal aneurysm formation. Rupture is the
      main complication that occurs in 3%-10% of the cases. We describe a case with a
      proximal splenic artery aneurysm. To preserve splenic function and reduce the
      risk of aneurysmal rupture, we used stent-graft to embolize the aneurysm treated
      percutaneously. The follow up of patient was uneventful after embolization.
      Endovascular embolization of the splenic artery aneurysm may prevent the need for
      emergency surgery and also offer an effective alternative surgical treatment.

PMID- 15957102
TI  - Regulation of gut function varies with life-history traits in chuckwallas
      (Sauromalus obesus: Iguanidae).
AB  - We examined the effects of hibernation and fasting on intestinal glucose and
      proline uptake rates of chuckwallas (Sauromalus obesus) and on the size of organs
      directly or indirectly related to digestion. These lizards show geographic
      variation in body size and growth rate that parallels an elevational gradient in
      our study area. At low elevation, food is available only for a short time during
      the spring; at high elevation, food may also be available during summer and
      autumn, depending on rainfall conditions in a given year. We hypothesized that
      low-elevation lizards with a short season of food availability would show more
      pronounced regulation of gut size and function than high-elevation lizards with
      prolonged or bimodal food availability. Hibernating lizards from both elevations
      had significantly lower uptake rates per milligram intestine for both nutrients,
      and lower small intestine mass, than active lizards. The combination of these two
      effects resulted in significantly lower total nutrient uptake in hibernating
      animals compared to active ones. The stomach, large intestine, and cecum showed
      lower masses in hibernators, but these results were not statistically
      significant. The heart, kidney, and liver showed no difference in mass between
      hibernating and nonhibernating animals. Lizards from low elevations with a short
      growing season also showed a greater increase in both uptake rates and small
      intestine mass from the hibernating to the active state, compared to those from
      high elevations with longer growing seasons. Thus, compared to those from long
      growing season areas, lizards from short growing season areas have equal uptake
      capacity during hibernation but much higher uptake capacity while active and
      feeding. This pattern of regulation of gut function may or may not be an adaptive
      response, but it is consistent with variation in life-history characteristics
      among populations. In areas with a short season, those lizards that can extract
      nutrients quickly and then reduce the gut will be favored; in areas where food
      may be available later in the year, those lizards that maintain an active gut
      would be favored. While other researchers have found much greater magnitudes of
      gut regulation when making comparisons among species, we find the different
      patterns of change in gut function between different populations of chuckwallas
      particularly intriguing because they occur within a single species.

PMID- 15957103
TI  - Development of the blood and muscle oxygen stores in gray seals (Halichoerus
      grypus): implications for juvenile diving capacity and the necessity of a
      terrestrial postweaning fast.
AB  - To successfully transition from nursing to foraging, phocid seal pups must
      develop adequate diving physiology within the limited time between birth and
      their first independent foraging trip to sea. We studied the postpartum
      development of oxygen stores in gray seals (Halichoerus grypus, n=40) to better
      understand the ontogeny of diving capacity in phocids. Hemoglobin (Hb),
      hematocrit (Hct), blood volume (BV), and myoglobin (Mb) levels in newborn (3 d
      postpartum [DPP]) and newly weaned (17+/-0.4 DPP) pups were among the lowest
      measured across age classes. During the pups' terrestrial postweaning fast (PWF),
      Hb, Hct, mass-specific BV, and Mb increased by 28%, 21%, 13%, and 29%,
      respectively, resulting in a 35% increase in total body mass-specific oxygen
      stores and a 23% increase in calculated aerobic dive limit (CADL). Although Hb
      and Hct levels at the end of the PWF were nearly identical to those of yearlings,
      total body mass-specific oxygen stores and CADL of weaned pups departing for sea
      were only 66%-67% and 32%-62%, respectively, of those for yearlings and adult
      females. The PWF represents an integral component of the physiological
      development of diving capacity in phocids; however, newly independent phocids
      still appear to have limited diving capabilities at the onset of foraging.

PMID- 15957104
TI  - Juvenile southern elephant seals exhibit seasonal differences in energetic
      requirements and use of lipids and protein stores.
AB  - Growing juvenile animals undergo many morphological, physiological, and
      behavioural changes that influence their energetic requirements, patterns of
      energy use, and ultimately, their survival and reproductive success. We examined
      changes in mass loss and body composition of juvenile southern elephant seals (1-
      and 2-yr-olds) during their two annual haul-outs. At the start and end of the
      midyear and molt haul-outs, we caught, weighed, and measured 41 and 14 seals,
      respectively. We measured blubber depth using ultrasound to estimate body
      composition (lean and adipose tissue mass). Using energy densities of the adipose
      and lean tissue, we calculated total, lean, and adipose mass changes and energy
      expenditure. While molting, juvenile seals used more energy than during the
      midyear, which is related to the increased use of lean tissue for hair and skin
      regeneration. The amount of energy used increases with mass as individuals
      mature. We found sexual differences in energy use where females retained greater
      fat reserves than males by utilizing more lean tissue. These differences are most
      likely related to haul-out function and behavior, growth, and earlier development
      of females toward sexual maturity.

PMID- 15957105
TI  - Physical, physiological, and behavioral correlates of musth in captive African
      elephants (Loxodonta africana).
AB  - Although musth in male African elephants (Loxodonta africana) is known to be
      associated with increased aggressiveness, urine dribbling (UD), temporal gland
      secretion (TGS), and elevated androgens, the temporal relationship between these
      changes has not been examined. Here, we describe the pattern of musth-related
      characteristics in 14 captive elephant bulls by combining long-term observations
      of physical and behavioral changes with physiological data on testicular and
      adrenal function. The length of musth periods was highly variable but according
      to our data set not related to age. Our data also confirm that musth is
      associated with elevated androgens and, in this respect, show that TGS and UD are
      downstream effects of this elevation, with TGS responding earlier and to lower
      androgen levels than UD. Because the majority of musth periods were associated
      with a decrease in glucocorticoid levels, our data also indicate that musth does
      not represent a physiological stress mediated by the hypothalamic-pituitary
      adrenal axis. Furthermore, we demonstrate that the occurrence of musth is
      associated with increased aggression and that this is presumably androgen
      mediated because aggressive males had higher androgen levels. Collectively, the
      information generated contributes to a better understanding of what characterizes
      and initiates musth in captive African elephants and provides a basis for further
      studies designed to examine in more detail the factors regulating the intensity
      and duration of musth.

PMID- 15957106
TI  - Functional roles for the compartmentalization of the subcutaneous lymphatic sacs
      in anuran amphibians.
AB  - Compliance of the subcutaneous lymph sacs of the hindlimbs increases from distal
      to proximal, as does limb segment mass (and presumably rate of lymph formation),
      for the semiaquatic bullfrog Rana catesbeiana and the cane toad Bufo marinus but
      not the aquatic clawed toad Xenopus laevis. Subcutaneous lymph-sac compliances
      vary interspecifically. The distal-to-proximal increase in lymph-sac compliance
      and estimates of lymph formation rate in the various hindlimb segments indicate
      that partitioning of hindlimb subcutaneous lymphatic sacs establishes a
      differential decrease in the intra-lymph-sac pressure for R. catesbeiana and B.
      marinus. These pressure differentials constitute a "compliance pump" that drives
      distal-to-proximal intersac lymph flow. The compliance pump alone explains
      lymphatic return for the aquatic frog X. laevis but does not explain how lymph
      would reach the dorsally located lymph hearts for terrestrial anurans, so we
      hypothesize that skeletal muscle pumps return lymph from the femoral and pubic
      lymph sacs to the lymph heart. This is a fundamentally different role of the
      subcutaneous lymph-sac system than has been previously proposed. We suggest that
      the more proximal subcutaneous lymph sacs are important for fluid storage because
      they have a relatively high compliance.

PMID- 15957107
TI  - Do changing moisture levels during incubation influence phenotypic traits of
      hatchling snakes (Tropidonophis mairii, Colubridae)?
AB  - Phenotypic traits (e.g., size, strength, speed) of hatchlings in many reptile
      species are influenced by hydric conditions in the nest. Previous experiments
      have focused on comparisons between eggs maintained under constant (but
      different) conditions, but eggs in natural nests frequently experience strong
      temporal shifts in soil water content during incubation. Keelback snakes
      (Tropidonophis mairii) in the Australian wet-dry tropics nest over most of the
      year, so early nests experience decreasing water availability during development,
      late nests experience increases, and others (midyear) remain stable in this
      respect. We mimicked these three conditions and incubated 54 eggs (nine from each
      of six clutches) in a split-clutch design to maintain the same average water
      content but with differing trajectories through incubation. The experimental
      treatments significantly affected the total amount of water taken up by the eggs
      (and thus final egg mass), but incubation periods were unaffected. Hatchling size
      but not strength showed minor but statistically significant effects of incubation
      regimes. The ability of keelback eggs to take up excess water whenever it becomes
      available (either early or late in development) and to retain it even when
      conditions change buffers embryogenesis effectively (but not completely) against
      fluctuations in soil water conditions.

PMID- 15957108
TI  - Testosterone inhibits growth in juvenile male eastern fence lizards (Sceloporus
      undulatus): implications for energy allocation and sexual size dimorphism.
AB  - In the eastern fence lizard, Sceloporus undulatus, female-larger sexual size
      dimorphism develops because yearling females grow faster than males before first
      reproduction. This sexual growth divergence coincides with maturational increases
      in male aggression, movement, and ventral coloration, all of which are influenced
      by the sex steroid testosterone (T). These observations suggest that male growth
      may be constrained by energetic costs of activity and implicate T as a
      physiological regulator of this potential trade-off. To test this hypothesis, we
      used surgical castration and subsequent administration of exogenous T to alter
      the physiological and behavioral phenotypes of field-active males during the
      period of sexual growth divergence. As predicted, T inhibited male growth, while
      castration promoted long-term growth. Males treated with T also exhibited
      increased daily activity period, movement, and home range area. Food consumption
      did not differ among male treatments or sexes, suggesting that the inhibitory
      effects of T on growth are mediated by patterns of energy allocation rather than
      acquisition. On the basis of estimates derived from published data, we conclude
      that the energetic cost of increased daily activity period following T
      manipulation is sufficient to explain most (79%) of the associated reduction in
      growth. Further, growth may have been constrained by additional energetic costs
      of increased ectoparasite load following T manipulation. Similar studies of the
      proximate behavioral, ecological, and physiological mechanisms involved in growth
      regulation should greatly improve our understanding of sexual size dimorphism.

PMID- 15957109
TI  - Morphometric comparison of the respiratory organs in the South American lungfish
      Lepidosiren paradoxa (Dipnoi).
AB  - In light of the relationship of lungfish to the origin of tetrapods, information
      on the respiratory biology of lungfish can give insight into the functional
      morphological and physiological prerequisites for the conquest of land by the
      first tetrapods. Stereological methods were employed in order to determine the
      respiratory surface area and thickness of the water-blood barrier or air-blood of
      the gills, lungs, and skin, respectively, of the South American lungfish
      Lepidosiren paradoxa. The morphometric diffusing capacity was then determined by
      multiplying by the appropriate Krogh diffusion constants (K). Our results
      indicate a total diffusing capacity of all respiratory organs of 0.11 mL min(-1)
      mmHg(-1) kg(-1), which is more than twice the value of the physiological
      diffusion capacity (approximately 0.04 mL min(-1) mmHg(-1) kg(-1)). Of this,
      99.15% lies in the lungs, 0.85% in the skin, and only 0.0013% in the gills. Since
      K for CO(2) is 20-25 times greater than for O(2), diffusing capacity of CO(2)
      through the skin is potentially important. That of the gills, however, is
      negligible, raising the question as to their function. Our results indicate that
      the morphological prerequisites for terrestrial survival with regard to
      supporting aerobic metabolism already existed in the lungfish.

PMID- 15957110
TI  - Pulmonary oxygen diffusing capacity of the South American lungfish Lepidosiren
      paradoxa: physiological values by the Bohr method.
AB  - Lungfish (Dipnoi) may represent the sister group to all land vertebrates and are
      therefore important for reconstructing the conquest of land by tetrapods. We
      determined venous and arterial blood gases, pulmonary O(2) uptake, and the form
      of the hemoglobin-O(2) dissociation curves in the South American lungfish
      Lepidosiren paradoxa. Measurements were performed at 25 degrees and 35 degrees C.
      Based on this information, we calculated its pulmonary O(2) diffusing capacity
      (D(L)O(2)), using the Bohr integration procedure. D(L)O(2) increased with
      temperature to reach about 0.04 mL stpd kg(-1) min(-1) mmHg(-1) at 35 degrees C.
      This value represents about 40% of the morphometric diffusing capacity and is
      similar to physiological values in some amphibians and reptiles.

PMID- 15957111
TI  - Variable effects of yolk androgens on growth, survival, and immunity in eastern
      bluebird nestlings.
AB  - Female birds allocate androgens differentially within and among clutches, and it
      has been suggested that this is a strategy to maximize reproductive success. Only
      a few studies, however, have examined the effects of yolk testosterone (T) on the
      growth and development of nestlings, and none have reported on the immunological
      effects of yolk T nor have they examined several different effects in the same
      nestlings. To examine the effects of yolk T on nestling eastern bluebirds, we
      administered two doses of exogenous T to bluebird eggs and measured the growth
      and immunological responsiveness in the resulting nestlings. We found that yolk T
      is detrimental to developing embryos, with hatching success decreasing with
      increasing doses of yolk T. Moderate doses of yolk T stimulated skeletal growth
      during the embryonic period, while high doses of yolk T resulted in nestlings
      that weighed more and were more mature at fledging but had a compromised T-cell
      immune response to phytohemagglutinin. These data suggest that the alteration of
      reproductive success through the allocation of yolk T is a complicated phenomenon
      that involves the integration of several physiological effects.

PMID- 15957112
TI  - Metabolic and ventilatory acclimatization to cold stress in house sparrows
      (Passer domesticus).
AB  - Passerines that overwinter in temperate climates undergo seasonal acclimatization
      that is characterized by metabolic adjustments that may include increased basal
      metabolic rate (BMR) and cold-induced summit metabolism (M(sum)) in winter
      relative to summer. Metabolic changes must be supported by equivalent changes in
      oxygen transport. While much is known about the morphology of the avian
      respiratory system, little is known about respiratory function under extreme cold
      stress. We examined seasonal variation in BMR, M(sum), and ventilation in
      seasonally acclimatized house sparrows from Wisconsin. BMR and M(sum) increased
      significantly in winter compared with summer. In winter, BMR increased 64%, and
      M(sum) increased 29% over summer values. The 64% increase in winter BMR is the
      highest recorded for birds. Metabolic expansibility (M(sum)/BMR) was 9.0 in
      summer and 6.9 in winter birds. The metabolic expansibility of 9.0 in summer is
      the highest yet recorded for birds. Ventilatory accommodation under helox cold
      stress was due to changes in breathing frequency (f), tidal volume, and oxygen
      extraction efficiency in both seasons. However, the only significant difference
      between summer and winter ventilation measures in helox cold stress was f. Mean f
      in helox cold stress for winter birds was 1.23 times summer values.

PMID- 15957113
TI  - Chick development in free-living great tits Parus major in relation to calcium
      availability and egg composition.
AB  - Evidence from a number of avian studies suggests that limitation of exogenous
      calcium (Ca) may reduce egg quality and retard nestling growth. However, it is
      poorly understood whether reduction in chick growth in Ca-poor areas is due to
      insufficient intake of dietary Ca or caused by maternal Ca limitation mediated
      through subtle changes in composition of eggs. In this study, we provide new
      evidence that Ca availability during egg formation may indeed affect egg
      composition and influence chick development of the great tit Parus major at early
      developmental stages. Ca-supplemented birds breeding in base-poor pine forests
      produced eggs with elevated yolk Ca concentration compared with controls, while
      no such effect of supplementation was detected in case of eggshell thickness.
      Nestling tarsus length in the first half of the nestling period was positively
      influenced by both yolk dry mass and yolk Ca concentration. The effect of
      supplementary Ca did not persist throughout the nestling period; initial effects
      of egg components disappeared as nestlings aged. We conclude that apparently
      normal eggs may harbor poor nutrient and mineral conditions for chick growth.
      Such subtle changes in composition of eggs can depress chick growth, especially
      in harsh years.

PMID- 15957114
TI  - The cost of chronic stress: impacts of a nonhabituating stress response on
      metabolic variables and swimming performance in sturgeon.
AB  - Metabolic scope for activity (MSA) and critical swimming velocity (U(crit)) were
      measured in green sturgeon exposed to two stressors daily for 28 consecutive
      days. The results were compared with unstressed fish in an effort to measure the
      "cost" of chronic stress. Chronic stress was simulated by exposing fish to a
      randomized order of acute stressors: a 5-min chasing stressor, a 10-min water
      depth reduction stressor, or a 5-min confinement stressor. The acute cortisol
      response to each stressor was initially determined, and the maintenance of that
      response was verified in 7-d intervals during the chronic stress regime. Exposure
      to the chronic stress regime resulted in a 25% reduction of MSA caused by
      significantly increased maintenance metabolic rate (0.27+/-0.01 vs. 0.19+/-0.02
      mg O(2) h(-1) g(-1), chronic and control fish, respectively) but did not affect
      the U(crit) of sturgeon. In addition, a 50% reduction in liver glycogen levels
      and a twofold increase of resting plasma glucose levels were measured in
      chronically stressed fish. We conclude that our chronic stress regime resulted in
      a significant maintenance cost to green sturgeon, possibly because of their
      inability to habituate to the stressors, but did not decrease their swimming
      performance.

PMID- 15957115
TI  - Marine (Taeniura lymma) and freshwater (Himantura signifer) elasmobranchs
      synthesize urea for osmotic water retention.
AB  - The objective of this study was to elucidate whether the marine blue-spotted
      fantail ray, Taeniura lymma, and the freshwater white-edge whip ray, Himantura
      signifer, injected with NH(4)Cl intraperitoneally would excrete the majority of
      the excess ammonia as ammonia per se to ameliorate ammonia toxicity despite being
      ureogenic. To examine the roles of urea and the ornithine-urea cycle,
      experimental fishes were exposed to salinity changes after being injected with
      NH(4)Cl. The ammonia excretion rates of the marine ray, T. lymma, injected with
      NH(4)Cl followed by exposure to seawater (30 per thousand) or diluted seawater
      (25 per thousand) increased 13-fold and 10-fold, respectively, within the first 3
      h. Consequently, the respective percentage of nitrogenous wastes excreted as
      ammonia were 55% and 65% compared with 21% of the saline-injected control,
      indicating that T. lymma became apparently ammonotelic after injection with
      NH(4)Cl. By hour 6, large portions (70%-85%) of the ammonia injected into T.
      lymma exposed to seawater or diluted seawater had been excreted, and T. lymma
      excreted much more nitrogenous wastes (135%-180%), in excess of the ammonia
      injected into the fish, during the 24-h period. For T. lymma exposed to seawater,
      a small portion (30%) of the ammonia injected into the fish was detoxified to
      urea during the first 6 h, but there was an apparent suppression of urea
      synthesis thereafter, contributing partially to the large decrease (19%) in urea
      contents in its muscle at hour 24. A major contributing factor to the decrease in
      urea content was a reduction in ammonia production, as indicated by a large
      deficit between urea loss in the muscle and excess ammonia accumulated plus
      excess nitrogen excreted in the experimental fish. The freshwater ray, H.
      signifer, injected with NH(4)Cl followed by exposure to freshwater (0.7 per
      thousand) or brackish water (10 per thousand) was capable of excreting all the
      ammonia injected into the body, mainly as ammonia, within 12 h. Like T. lymma, it
      also excreted the injected ammonia mainly as ammonia during the first 3 h
      postinjection. During this period, the percentage of the injected ammonia
      excreted in fish exposed to brackish water (28.4%+/-4.6%) was significantly lower
      than those exposed to freshwater (56.1%+/-8.26%). In contrast, the percentage of
      nitrogenous wastes being excreted as urea in the former (38.4%) was significantly
      greater than that in the latter (14.1%). These results suggest that a portion of
      the ammonia injected into the fish was turned into urea, and urea synthesis was
      increased transiently in fish exposed to brackish water during the initial
      postinjection period. However, urea was not retained effectively by H. signifer.
      Taken together, these results suggest that the primary function of the ornithine
      urea cycle in ureogenic marine and freshwater elasmobranchs is to synthesize urea
      for osmotic water retention and not for ammonia detoxification.

PMID- 15957116
TI  - Nitrogen metabolism and excretion in the swamp eel, Monopterus albus, during 6 or
      40 days of estivation in mud.
AB  - Monopterus albus inhabits muddy ponds, swamps, canals, and rice fields, where it
      can burrow into the moist earth, and it survives for long periods during the dry
      summer season. However, it had been reported previously that mortality increased
      when M. albus was exposed to air for 8 d or more. Thus, the objective of this
      study was to elucidate the strategies adopted by M. albus to defend against
      ammonia toxicity during 6 or 40 d of estivation in mud and to evaluate whether
      these strategies were different from those adopted by fish to survive 6 d of
      aerial exposure. Ammonia and glutamine accumulations occurred in the muscle and
      liver of fish exposed to air (normoxia) for 6 d, indicating that ammonia was
      detoxified to glutamine under such conditions. In contrast, ammonia accumulation
      occurred only in the muscle, with no increases in glutamine or glutamate contents
      in all tissues, of fish estivated in mud for 6 d. Similar results were obtained
      from fish estivated in mud for 40 d. While estivating in mud prevented excessive
      water loss through evaporation, M. albus was exposed to hypoxia, as indicated by
      significant decreases in blood P(O(2)), muscle energy charge, and ATP content in
      fish estivated in mud for 6 d. Glutamine synthesis is energy intensive, and that
      could be the reason why M. albus did not depend on glutamine synthesis to defend
      against ammonia toxicity when a decrease in ATP supply occurred. Instead,
      suppression of endogenous ammonia production was adopted as the major strategy to
      ameliorate ammonia toxicity when M. albus estivated in mud. Our results suggest
      that a decrease in O(2) level in the mud could be a more effective signal than an
      increase in internal ammonia level during aerial exposure to induce a suppression
      of ammonia production in M. albus. This might explain why M. albus is able to
      estivate in mud for long periods (40 d) but can survive in air for only <10 d.

PMID- 15957117
TI  - The African sharptooth catfish Clarias gariepinus can tolerate high levels of
      ammonia in its tissues and organs during four days of aerial exposure.
AB  - The African sharptooth catfish Clarias gariepinus lives in freshwater, is an
      obligatory air breather, and can survive on land during drought. The objective of
      this study was to elucidate how C. gariepinus defends against ammonia toxicity
      when exposed to terrestrial conditions. During 4 d of aerial exposure, there was
      no accumulation of urea in its tissues, and the rate of urea excretion remained
      low. Thus, exposure to terrestrial conditions for 4 d did not induce ureogenesis
      or ureotely in C. gariepinus. Volatilization of NH(3) was not involved in
      excreting ammonia during aerial exposure. In addition, there were no changes in
      levels of alanine in the muscle, liver, and plasma of C. gariepinus; nor were
      there any changes in the glutamine levels in these tissues. However, there were
      extraordinarily high levels of ammonia in the muscle (14 micromol g(-1)), liver
      (18 micromol g(-1)), and brain (11 micromol g(-1)) of fish exposed to terrestrial
      conditions for 4 d. This is the first report on a fish adopting high tolerance of
      ammonia in cells and tissues as the single major strategy to defend against
      ammonia toxicity during aerial exposure. At present, it is uncertain how C.
      gariepinus tolerates such high levels of ammonia, especially in its brain, but it
      can be concluded that, contrary to previous reports on two air-breathing
      catfishes (Clarias batrachus and Heteropneustes fossilis) from India, C.
      gariepinus does not detoxify ammonia to urea or free amino acids on land.

PMID- 15957118
TI  - Antioxidant mechanisms of the Nereidid Laeonereis acuta (Anelida: Polychaeta) to
      cope with environmental hydrogen peroxide.
AB  - Hydrogen peroxide (H(2)O(2)) is a naturally occurring prooxidant molecule, and
      its effects in the macroinvertebrate infauna were previously observed. The
      existence of a gradient of antioxidant enzymes activity (catalase [CAT],
      glutathione peroxidase [GPx], superoxide dismutase [SOD], and glutathione-S
      transferase [GST]) and/or oxidative damage along the body of the estuarine
      polychaeta Laeonereis acuta (Polychaeta, Nereididae) was analyzed after exposure
      to H(2)O(2). Because this species secretes conspicuous amounts of mucus, its
      capability in degrading H(2)O(2) was studied. The results suggest that L. acuta
      deal with the generation of oxidative stress with different strategies along the
      body. In the posterior region, higher CAT and SOD activities ensure the
      degradation of inductors of lipid peroxidation such as H(2)O(2) and superoxide
      anion (O(2)(.-)). The higher GST activity in anterior region aids to conjugate
      lipid peroxides products. In the middle region, the lack of high CAT, SOD, or GST
      activities correlates with the higher lipid hydroperoxide levels found after
      H(2)O(2) exposure. Ten days of exposure to H(2)O(2) also induced oxidative stress
      (lipid peroxidation and DNA damage) in the whole animal paralleled by a lack of
      CAT induction. The mucus production contributes substantially to H(2)O(2)
      degradation, suggesting that bacteria that grow in this secretion provide this
      capability.

PMID- 15957119
TI  - Comparison of different approaches for the calculation of energy expenditure
      using doubly labeled water in a small mammal.
AB  - The doubly labeled water (DLW) method is an isotope-based technique for the
      estimation of the CO(2) production, and hence energy expenditure, of free-living
      animals and humans. Several methods are available for the calculation of CO(2)
      production from the isotope fluxes, depending on different assumptions about the
      behavior of isotopes during the elimination process. We used the DLW method to
      estimate the daily energy expenditures (DEE) of 55 field voles (Microtus
      agrestis) held in a captive facility at 8 degrees C. We calculated DEE using both
      plateau and intercept approaches for estimating the sizes of the isotope dilution
      spaces, three different assumptions about fractionation processes, and two ways
      of treating the different dilution spaces of the oxygen and hydrogen isotopes. We
      compared the resultant DEE estimates with metabolizable energy intake (MEI)
      measured during a 3-d feeding trial immediately before the DLW measurements,
      during which the animals were in energy balance. By making different assumptions
      about the apparent energy absorption efficiency, we generated a range of direct
      estimates of MEI. When we compared DEE and MEI, we found that the two-pool model
      formulations consistently underestimated energy demands by up to 29.8%, depending
      on the assumptions made in the reference calculation. However, while our data
      suggest that some correction for fractionation is necessary, with the present
      data we were unable to separate the two most common treatments of fractionation.
      These data strongly support the previous suggestion that for small mammals single
      pool models provide more accurate estimates of energy demands than two-pool
      formulation of the DLW method.

PMID- 15957120
TI  - Gabapentin-induced myopathy in 2 patients on short daily hemodialysis.
AB  - Gabapentin is an antiepileptic medication that also has been used for restless
      legs syndrome. The mechanism of action is unknown. The most commonly reported
      adverse effects of this medication include somnolence, dizziness, ataxia,
      fatigue, nystagmus, and tremor. Myalgia has been reported in 2% of gabapentin
      users compared with 1.9% of patients in placebo-controlled add-on trials. Two
      patients on short daily hemodialysis therapy developed neuromuscular symptoms and
      an elevation in creatine kinase levels after starting gabapentin therapy. To our
      knowledge, this is the first case report of an increase in creatine kinase level
      after the administration of gabapentin.

PMID- 15957121
TI  - Chromophobe renal cell carcinoma in a pediatric living-related kidney transplant
      recipient.
AB  - Renal cell carcinoma can occur in children who have received renal allografts
      from adults. Chromophobe renal cell carcinoma is a rare variant of renal
      carcinoma with distinct histochemical, ultrastructural, and genetic
      characteristics. We describe the incidental finding of a chromophobe renal cell
      carcinoma in a 13 1/2-year-old boy 5 years after receiving a living-related renal
      transplant. This tumor was found by serendipity during the evaluation of fever
      and inguinal lymphadenopathy, with the presumptive diagnosis of
      posttransplantation lymphoproliferative disorder. The patient was found to have
      cat-scratch disease. A renal cell carcinoma should be considered in the
      differential diagnosis of a pediatric recipient of an adult kidney with an
      incidental finding of a tumor in the graft.

PMID- 15957122
TI  - A case of thoracic hemorrhage due to ectopic parathyroid hyperplasia with chronic
      renal failure.
AB  - We report a case of secondary hyperparathyroidism in a 53-year-old man who had
      thoracic hemorrhage originating from an ectopic thymic parathyroid gland tumor.
      He was on long-term hemodialysis treatment and had persistent secondary
      hyperparathyroidism caused by 3 swollen parathyroid glands around the thyroid
      gland and a mediastinal ectopic parathyroid gland tumor. Parathyroidectomy and
      removal of the mediastinal tumor were planned. Preoperative chest x-ray and a
      computed tomographic scan obtained just before surgery showed left pleural
      effusion. Furthermore, diagnostic thoracentesis yielded hemorrhagic exudative
      fluid. Thoracoscopy confirmed the presence of a mediastinal tumor lesion that was
      bleeding into the thoracic cavity. The tumor was resected using thoracoscopic
      surgery, and ectopic thymic parathyroid gland hyperplasia associated with
      hemorrhage was pathologically diagnosed. A postoperative diagnostic chest
      computed tomographic scan and technetium 99m 2-methoxyisobutyl isonitrile
      scintigraphy showed successful removal of the ectopic parathyroid gland tumor.
      Subsequently, the secondary hyperparathyroidism could be clinically controlled by
      medical treatment, and total parathyroidectomy has been postponed indefinitely.
      We consider that hemorrhage from the ectopic parathyroid gland tumor resulted in
      thoracic bleeding. To our knowledge, this is the first case report of secondary
      hyperparathyroidism with thoracic hemorrhage originating from an ectopic
      mediastinal parathyroid gland.

PMID- 15957123
TI  - Quiz page. Renal "milk of calcium" syndrome.

PMID- 15957124
TI  - Rapid resolution of EPO-induced pure red cell aplasia after a course of
      immunoadsorption therapy using protein A columns.
AB  - Pure red cell aplasia (PRCA) is a rare, but important, complication of
      erythropoietin (EPO) replacement therapy in patients with renal disease. There is
      no consensus about the best way to treat this condition; however, recent reports
      indicated that immunosuppressive therapy is beneficial. We report a patient with
      EPO-induced PRCA treated with a regimen initially designed for antifactor VIII
      antibodies in patients with hemophilia. This regimen consists of immunoadsorption
      therapy using protein A columns, followed by oral prednisolone and single bolus
      infusions of intravenous immunoglobulin G and cyclophosphamide. Shortly after the
      course, a swift and rapid increase in reticulocyte count was evident; the patient
      became transfusion independent and has remained so during 2 years of follow-up.
      By means of this report, we wish to encourage others to consider this option when
      first-line treatments fail.

PMID- 15957125
TI  - Arterial stiffness in renal patients: an update.
AB  - According to recent data, arterial stiffness is a major independent risk factor
      for cardiovascular morbidity and mortality in both the general and renal
      populations. Because of several factors (vascular calcifications among them),
      large arteries are stiffer in patients with chronic kidney disease compared with
      the nonrenal population, contributing to the enormous cardiovascular mortality in
      renal patients. This review briefly analyzes methods for determination of
      arterial stiffness, focusing on 2 parameters, pulse wave velocity and the
      augmentation index, particularly useful in assessing arterial compliance in renal
      patients. Effects of different methods of renal replacement therapy on arterial
      wall properties also are discussed. Finally, the most promising novel and/or
      potential therapies regarding reduction of arterial stiffness in renal patients
      are reviewed.

PMID- 15957126
TI  - Metabolic acidosis of CKD: diagnosis, clinical characteristics, and treatment.
AB  - Metabolic acidosis is noted in the majority of patients with chronic kidney
      disease (CKD) when glomerular filtration rate (GFR) decreases to less than 20% to
      25% of normal, although as many as 20% of individuals can have acid-base
      parameters close to or within the normal range. Acidosis generally is mild to
      moderate in degree, with plasma bicarbonate concentrations ranging from 12 to 22
      mEq/L (mmol/L), and it is rare to see values less than 12 mEq/L (mmol/L) in the
      absence of an increased acid load. Degree of acidosis approximately correlates
      with severity of renal failure and usually is more severe at a lower GFR. The
      metabolic acidosis can be of the high-anion-gap variety, although anion gap can
      be normal or only moderately increased even with stage 4 to 5 CKD. Several
      adverse consequences have been associated with metabolic acidosis, including
      muscle wasting, bone disease, impaired growth, abnormalities in growth hormone
      and thyroid hormone secretion, impaired insulin sensitivity, progression of renal
      failure, and exacerbation of beta 2 -microglobulin accumulation. Administration
      of base aimed at normalization of plasma bicarbonate concentration might be
      associated with certain complications, such as volume overload, exacerbation of
      hypertension, and facilitation of vascular calcifications. Whether normalization
      of plasma bicarbonate concentrations in all patients is desirable therefore
      requires additional study. In the present review, we describe clinical and
      laboratory characteristics of metabolic acidosis, discuss potential adverse
      effects, and address benefits and complications of therapy.

PMID- 15957127
TI  - Home blood pressure monitoring in CKD.
AB  - BACKGROUND: Blood pressure (BP) control is the mainstay of stalling the
      progression of cardiorenal disease, yet the performance characteristics of BPs
      obtained in the clinic (CBPs) by routine or standardized methods or at home (HBP)
      in diagnosing hypertension or assessing its control are unknown. METHODS: Two
      hundred thirty-two patients (20% black; 4% women; mean age, 67 years; 35% with
      diabetes) with chronic kidney disease (CKD) underwent a single 24-hour ambulatory
      BP (ABP) monitoring (ABPM) and concomitant recording of CBP and HBP for 1 week.
      Hypertension is defined as systolic BP of 130 mm Hg or greater or diastolic BP of
      80 mm Hg or greater on average awake 24-hour ABPM. RESULTS: Average ABP was 135.2
      +/- 15.9/75.6 +/- 11.0 mm Hg. Thirty-five percent of patients had isolated
      systolic hypertension; 3%, isolated diastolic hypertension; 27%, combined
      systolic and diastolic hypertension; and 35%, normotension or well-controlled BP.
      The prevalence of "white-coat effect" was estimated as 28% to 30% by means of
      CBPs and 24% by means of HBPs. Well-controlled BP in the clinic, but poorly
      controlled BP by means of ABPM, masked hypertension, was seen in 26% to 29% by
      means of CBPs, but only 13% with HBP monitoring. CONCLUSION: In patients with
      CKD, HBP is superior in reducing the misclassification of hypertension caused by
      the white-coat effect and masked hypertension commonly seen with CBPs. An average
      HBP of approximately 140/80 mm Hg appears to be the best correlate of
      hypertension defined by means of ABPM.

PMID- 15957128
TI  - Outcomes after percutaneous coronary interventions in patients with CKD: improved
      outcome in the stenting era.
AB  - BACKGROUND: Percutaneous coronary intervention (PCI) with stenting reduces
      adverse events in the general population compared with balloon angioplasty. The
      benefit of stents in high-risk patients normally excluded from clinical trials
      has not been well studied. Outcomes after PCIs in patients with chronic kidney
      disease (CKD) before and after widespread use of stents were compared. METHODS:
      All patients undergoing PCIs at our center within 2 periods selected for high and
      low stent use were included. Demographic, kidney and cardiac function, and PCI
      data were collected. Kaplan-Meier curves were constructed, and Cox proportional
      hazards analysis was used to assess the effect of high stent use on major adverse
      cardiac event, a composite of cardiac revascularization, myocardial infarction,
      or death 3 years after PCI. RESULTS: A total of 1,879 patients (780 patients, low
      stent use; 1,099 patients, high stent use; 18% and 94.1% stent use, respectively)
      with a mean age of 63 years, 73% men, and 26% of patients with a glomerular
      filtration rate less than 60 mL/min were included. At baseline, there was a
      greater prevalence of severe CKD, cardiac risk factors, and cardiovascular
      disease in the high-stent-use cohort. Major adverse cardiac events were reduced
      in the contemporary cohort (hazard ratio, 0.61; 95% confidence interval, 0.52 to
      0.72); this benefit extended across all stages of kidney function. CONCLUSION:
      Patients with CKD undergoing PCI in the stenting era show improved outcomes.
      Additional studies are needed to determine optimal revascularization strategies
      in patients with CKD.

PMID- 15957129
TI  - Maternal urine albumin excretion and pregnancy outcome.
AB  - BACKGROUND: Vascular dysfunction has been hypothesized as a causal pathway for
      preeclampsia, impaired fetal growth, and early parturition. The relationship
      between increased urine albumin excretion (albuminuria), a marker of endothelial
      dysfunction, and preterm birth has not been fully evaluated. METHODS: We
      conducted a nested case-control study of 404 pregnancies from 1998 to 2000 within
      the Pregnancy, Infection and Nutrition cohort. Cases consisting of live births
      delivered before 37 weeks of gestation (preterm birth, n = 111) were compared
      with term births from the same cohort (n = 293). Albumin-creatinine ratio (in
      milligrams per gram) was measured in urine collected around 27 weeks of
      gestation. We compared risks for preterm birth in mothers with albuminuria with
      albumin levels of 3 to 20 mg/g and greater than 20 mg/g relative to those with
      albumin levels less than 3 mg/g by using logistic regression. RESULTS: Median
      albuminuria was albumin level of 2.7 and 4.3 mg/g for term and preterm births,
      respectively. Albuminuria was strongly associated with preterm birth in a dose
      response fashion, with adjusted odds ratios of 1.9 (95% confidence interval, 1.1
      to 3.1) and 4.7 (95% confidence interval, 1.7 to 12.6) for albuminuria with
      albumin of 3 to 20 mg/g and greater than 20 mg/g, respectively. The association
      was present for both spontaneous and medically induced preterm births, but the
      effect was decreased and the dose-response relationship was eliminated by
      excluding high-risk groups and those with pregnancy complications. CONCLUSION:
      Low levels of albuminuria are associated with preterm birth. The mechanism
      underlying this association warrants additional exploration.

PMID- 15957130
TI  - The relationship between albuminuria and hormone therapy in postmenopausal women.
AB  - BACKGROUND: Elevated urinary albumin excretion and hormone therapy (HT) are
      associated with increased risk for cardiovascular events. We assessed the
      relationship between albuminuria and the use of hormonal preparations in
      postmenopausal women. METHODS: Data from the Insulin Resistance Atherosclerosis
      Study were obtained at baseline and 5-year follow-up for analysis. The
      generalized estimating equation procedure accounting for repeated measures was
      used for this analysis. HT was the main predictor variable, and log(e) urine
      albumin-creatinine ratio (ACR) was the main outcome variable. RESULTS: Four
      hundred ninety-one menopausal women were included in the analysis, 36% (n = 179)
      of whom received HT (either oral estrogen, progesterone, or combination therapy).
      At baseline, abnormal albuminuria (ACR > or = 25 mg/g) was present in 11% of
      women on HT and 17% not on HT (P = 0.02). After adjusting for demographics, the
      presence of diabetes and hypertension, and kidney function, HT was associated
      with a 19% reduction in ACR (P = 0.008) and an odds ratio of 0.67 (95% confidence
      interval, 0.43 to 1.01; P = 0.06) for the presence of abnormal albuminuria. Other
      predictors of abnormal albuminuria included diabetes, blood pressure, and
      triglyceride level. CONCLUSION: Results of this study suggest that HT is
      associated with a reduction in urinary albumin excretion in postmenopausal women.

PMID- 15957131
TI  - Prevalence of calcidiol deficiency in CKD: a cross-sectional study across
      latitudes in the United States.
AB  - BACKGROUND: Recent Kidney Disease Outcomes Quality Initiative guidelines have
      raised concerns of 25-hydroxyvitamin D, or calcidiol, insufficiency and
      deficiency in patients with chronic kidney disease (CKD) not yet on dialysis
      therapy; however, no cross-sectional study across latitudes has been performed to
      support this assertion. METHODS: Baseline screening data from a prospective study
      were used to determine calcidiol levels in subjects with moderate to severe CKD
      not yet on dialysis therapy from 12 geographically diverse regions of the United
      States. Calcidiol deficiency is defined as levels less than 10 ng/mL (< 25
      nmol/L), and insufficiency, as levels of 10 to 30 ng/mL (25 to 75 nmol/L).
      RESULTS: Two hundred one subjects with a mean age 65 +/- 13 years and calculated
      glomerular filtration rate (GFR) of 27 +/- 11 mL/min (0.45 mL/s) were evaluated.
      Overall mean calcidiol level was 19.4 +/- 13.6 ng/mL (48 +/- 34 nmol/L), with a
      range of 0 to 65 ng/mL (0 to 162 nmol/L). Only 29% and 17% of subjects with
      moderate and severe CKD had sufficient levels, respectively. Mean calcidiol
      levels were less than sufficient levels in all geographic locations tested.
      Multivariate analysis found log calcidiol level correlated with calcium level (P
      = 0.016), log calcitriol level (P = 0.024), sex (P = 0.041), geographic location
      (P = 0.045), and inverse intact parathyroid hormone level (P = 0.013), but not
      calculated GFR or phosphorous level. Calcidiol levels changed modestly in 18
      patients who had calcidiol levels measured in winter and late summer after
      confirmed exposure to sunlight, with mean calcidiol levels of 17.9 +/- 11.7 to
      21.2 +/- 10.0 ng/mL (45 +/- 29 to 53 +/- 25 nmol/L; P = 0.015). CONCLUSION: This
      cross-sectional cohort study found a high prevalence of calcidiol deficiency and
      insufficiency in patients with moderate and severe CKD not on dialysis therapy
      regardless of geographic location.

PMID- 15957132
TI  - Expression of gremlin, a bone morphogenetic protein antagonist, in human diabetic
      nephropathy.
AB  - BACKGROUND: We report the induction of gremlin, a bone morphogenetic protein
      antagonist, in cultured human mesangial cells exposed to high glucose and
      transforming growth factor beta (TGF-beta) levels in vitro and kidneys from
      diabetic rats in vivo. METHODS: Gremlin expression was assessed in human diabetic
      nephropathy by means of in situ hybridization, immunohistochemistry, and real
      time polymerase chain reaction and correlated with clinical and pathological
      indices of disease. RESULTS: Gremlin was not expressed in normal human adult
      kidneys. Conversely, abundant gremlin expression was observed in human diabetic
      nephropathy. Although some gremlin expression was observed in occasional
      glomeruli, gremlin expression was most prominent in areas of tubulointerstitial
      fibrosis, where it colocalized with TGF-beta expression. Gremlin messenger RNA
      levels correlated directly with renal dysfunction, determined by means of serum
      creatinine level, but not with proteinuria level. There was a strong correlation
      between gremlin expression and tubulointerstitial fibrosis score. CONCLUSION: In
      aggregate, these results indicate that the developmental gene gremlin reemerges
      in the context of tubulointerstitial fibrosis in diabetic nephropathy and
      suggests a role for TFG-beta as an inducer of gremlin expression in this context.

PMID- 15957133
TI  - Subcutaneous terbutaline use in CKD to reduce potassium concentrations.
AB  - BACKGROUND: Acute hyperkalemia is a frequent and potentially life-threatening
      medical problem in patients on maintenance hemodialysis therapy. beta-Adrenergic
      receptor (betaAR) stimulation causes potassium cellular influx and a decline in
      plasma potassium concentrations. Therefore, betaAR agonists are used in the
      treatment of patients with hyperkalemia. The goal of this study is to evaluate
      the utility of weight-based subcutaneous terbutaline dosing to reduce plasma
      potassium concentrations in a group of subjects with chronic kidney disease (CKD)
      requiring hemodialysis. METHODS: Fourteen subjects with CKD receiving long-term
      hemodialysis were administered terbutaline, 7 microg/kg, subcutaneously. Heart
      rate measurements and blood samples for potassium concentration determinations
      were made serially for 420 minutes. Effects of terbutaline on heart rate and
      potassium responses were determined in each subject. RESULTS: Terbutaline
      significantly reduced plasma potassium concentrations and significantly increased
      heart rates during the time course of the study (P < 0.001, repeated-measures
      analysis of variance). Mean reduction in peak potassium concentration (-1.31 +/-
      0.5 [SD] mEq/L) and increase in peak heart rate (25.8 +/- 10.5 beats/min) were
      significantly different from baseline (P < 0.001, baseline versus peak for both
      responses). No subject reported significant adverse effects. CONCLUSION:
      Administration of subcutaneous terbutaline obviates the need for intravenous
      access and should be considered as an alternative to nebulized or inhaled beta
      agonists to treat acute hyperkalemia in patients with CKD. As with the use of any
      beta-adrenergic agonist, close cardiovascular monitoring is necessary to avoid or
      minimize toxicity during therapy.

PMID- 15957134
TI  - A cognitive behavioral group approach to enhance adherence to hemodialysis fluid
      restrictions: a randomized controlled trial.
AB  - BACKGROUND: Adhering to fluid restrictions represents one of the most difficult
      aspects of the hemodialysis treatment regimen. This report describes a randomized
      controlled trial of a group-based cognitive behavioral intervention aimed at
      improving fluid-restriction adherence in patients receiving hemodialysis. It was
      hypothesized that the intervention would improve adherence, measured by means of
      interdialytic weight gain (IWG), without impacting negatively on psychosocial
      functioning. METHODS: Fifty-six participants receiving hemodialysis from 4 renal
      outpatient settings were randomly assigned to an immediate-treatment group (ITG;
      n = 29) or deferred-treatment group (DTG; n = 27). Participants were assessed at
      baseline, posttreatment, and follow-up stages. Treatment consisted of a 4-week
      intervention using educational, cognitive, and behavioral strategies to enhance
      effective self-management of fluid consumption. RESULTS: No significant
      difference in mean IWGs was found between the ITG and DTG during the acute-phase
      analysis (F(1,54) = 0.03; P > 0.05). However, in longitudinal analysis, there was
      a significant main effect for mean IWG (F(1.76,96.80) = 9.10; P < 0.001) and a
      significant difference between baseline and follow-up IWG values (t55 = 3.85; P <
      0.001), reflecting improved adherence over time. No adverse effects of treatment
      were indicated through measures of psychosocial functioning. Some significant
      changes were evidenced in cognitions thought to be important in mediating
      behavioral change. CONCLUSION: The current study provides evidence for the
      feasibility and effectiveness of applying group-based cognitive behavior therapy
      to enhance adherence to hemodialysis fluid restrictions. Results are discussed in
      the context of the study's methodological limitations.

PMID- 15957135
TI  - Stroke in patients on maintenance hemodialysis: a 22-year single-center study.
AB  - BACKGROUND: Few studies have reported the detailed clinical features of stroke in
      patients with end-stage renal disease. We examined the frequency of the subtypes,
      mechanism, and outcome of stroke in patients receiving hemodialysis (HD).
      METHODS: We studied 151 consecutive patients who developed an acute stroke among
      the maintenance HD population in our kidney center during 22 years, divided into
      the initial 17-year (n = 61) and the more recent 5-year (n = 90) groups. For
      purposes of comparison, we also studied 1,017 stroke patients with normal renal
      function. RESULTS: Stroke patients receiving HD were younger (age, 64 +/- 10
      versus 67 +/- 13 years; P < 0.02) and more frequently had hypertension (87%
      versus 43%; P < 0.0001) and diabetes (53% versus 23%; P < 0.0001) compared with
      stroke patients with normal renal function. In the initial HD group, brain
      hemorrhage was the major subtype of stroke (52%), whereas in the more recent
      group, brain infarction (BI) replaced hemorrhage as the leading subtype (68%; P <
      0.005). In patients with BI, large-artery atherosclerosis was more prevalent in
      the more recent group than in the initial HD group (33% versus 12%; P < 0.05). A
      vertebrobasilar territory infarct was more prevalent for HD patients than for
      those with normal renal function (48% versus 33%; P < 0.05). BI (especially large
      artery atherosclerosis and cardioembolism) occurred more frequently during or
      less than 30 minutes after the dialysis procedure (34%) than brain hemorrhage
      (19%; P < 0.05). Receiving HD was an independent indicator for poor functional
      outcome and mortality after stroke. CONCLUSION: In our maintenance HD population,
      stroke showed several unique characteristics compared with the control
      population, including a predominance of vertebrobasilar arterial territory
      infarcts. The dialysis procedure itself seems to be associated more frequently
      with ischemic rather than hemorrhagic strokes.

PMID- 15957136
TI  - Nonfasting non-high-density lipoprotein cholesterol is adequate for lipid
      management in hemodialysis patients.
AB  - BACKGROUND: Guidelines for the management of dyslipidemia in patients with
      chronic kidney disease are based on results from the fasting lipid profile, which
      can be difficult to obtain from patients on an afternoon or night dialysis
      schedule. The present study tests the hypothesis that nonfasting non-high-density
      lipoprotein (HDL) cholesterol (total cholesterol-HDL cholesterol) results are
      similar to fasting non-HDL results as a basis for the management of dyslipidemia
      in hemodialysis patients. METHODS: Forty-eight long-term hemodialysis patients
      with a mean age of 63.6 years (42% with diabetes, 54% administered statins)
      participated in this study. For the lipid profile, blood samples were drawn after
      a 12-hour overnight fast (fasting) and again in a nonfasting state before the
      subsequent hemodialysis session. Data were analyzed by using paired t-test and
      regression analysis. RESULTS: Non-HDL cholesterol values were nearly identical
      regardless of whether the patient was fasting (r2 = 0.995). Only 2 patients (4%)
      had a nonfasting triglyceride (TG) level greater than 500 mg/dL (> 5.6 mmol/L),
      which would have required confirmation after an overnight fast. Non-HDL values
      had the greatest level of correlation (absolute relative difference, 5.7%). When
      comparing the subgroup of patients with a TG level less than 200 mg/dL (< 2.3
      mmol/L), nonfasting non-HDL cholesterol values identified 3 additional patients
      compared with fasting calculated low-density lipoprotein cholesterol for whom
      lipid-lowering therapy would have been introduced according to current
      guidelines. CONCLUSION: In our study, non-HDL cholesterol levels were equivalent
      whether evaluated in the fasting or nonfasting state. We recommend that
      nonfasting non-HDL cholesterol level be used for the management of dyslipidemia
      in hemodialysis patients without imposing a 12-hour fast period.

PMID- 15957137
TI  - High-calorie supplementation increases serum leptin levels and improves response
      to rHuEPO in long-term hemodialysis patients.
AB  - BACKGROUND: Dialysis patients with a high body mass index are less likely to
      experience severe anemia. Leptin, a hormone secreted by adipocytes, may have a
      role in protecting against renal anemia. The aim of the present study is to
      determine the effect of an increase in serum leptin levels by increasing energy
      intake on recombinant human erythropoietin (rHuEPO) response in long-term
      hemodialysis (HD) patients. METHODS: We enrolled 65 long-term HD patients to
      explore the association between leptin level and rHuEPO response by classifying
      them as either high- or low-leptin individuals (phase 1). Thereafter, 39 patients
      with malnutrition by means of Subjective Global Assessment were randomly assigned
      to high-energy and high-protein (an extra 475 kcal and 16.6 g of protein daily;
      group A; n = 12) or standard-energy, but high-protein (an extra 67.2 kcal and
      16.8 g of protein daily; group B; n = 27), supplementation for 12 weeks. Serial
      serum leptin levels, nutritional measures, and hematologic parameters were
      obtained. Age- and sex-matched well-nourished patients (group C; n = 16) not
      administered extra nutritional supplementation served as control subjects (phase
      2). RESULTS: In phase 1, a significantly lower erythropoietin dose, greater
      hematocrit, and better nutritional measures were observed in the high-leptin
      group (P < 0.001). In phase 2, there was a significant increase in body fat mass
      (P = 0.001) and median serum leptin levels (P < 0.001) in response to 12 weeks of
      high-energy supplementation in group A, accompanied by markedly improved
      erythropoiesis (P < 0.05) compared with groups B and C. CONCLUSION:
      Hyperleptinemia reflects better nutritional status and rHuEPO response in long
      term HD patients. Increasing energy intake improves erythropoiesis, which may be
      mediated in part by an increase in serum leptin levels.

PMID- 15957138
TI  - Infiltrating cell types in transplant glomerulitis: relationship to peritubular
      capillary C4d deposition.
AB  - BACKGROUND: Transplant glomerulitis may be part of the acute rejection process in
      some transplant recipients. Glomerular monocytes have been shown to be the
      predominant cell type in transplant glomerulitis associated with peritubular
      capillary C4d deposition. Whether this applies to peritubular capillary C4d
      negative (C4d-) biopsy specimens with transplant glomerulitis is unknown.
      METHODS: Forty-two biopsy specimens with acute rejection and transplant
      glomerulitis were immunostained for monocytes, T cells, and C4d. In each biopsy
      specimen, glomerular monocytes and T cells were counted, and mean numbers of
      monocytes per glomerulus and T cells per glomerulus were determined. RESULTS:
      Peritubular capillary C4d staining was present in 20 biopsy specimens (C4d
      positive [C4d+] group) and negative in 22 specimens (C4d- group). There was no
      significant difference between mean Banff 97 glomerular scores for the 2 groups
      (C4d+ , 1.60 +/- 0.80; C4d- , 1.77 +/- 0.90). Although the C4d+ group showed a
      significantly higher mean number of monocytes per glomerulus (3.01 +/- 2.35) than
      the C4d- group (0.95 +/- 1.00; P < 0.0001), the C4d- group showed a significantly
      higher mean number of T cells per glomerulus (4.05 +/- 3.05) than the C4d+ group
      (1.36 +/- 1.24; P = 0.0007). There were proportionately more C4d+ biopsy
      specimens with a monocyte-T-cell ratio greater than 1.0 (75%) than C4d- specimens
      (14%; P < 0.0001). Mean glomerular monocyte-T-cell ratio was 3.66 +/- 4.24 for
      the C4d+ group and 0.39 +/- 0.54 for the C4d- group; the difference was
      significant (P = 0.0009). CONCLUSION: In acute rejection with no peritubular
      capillary C4d deposition, the predominant infiltrating endocapillary cell in
      transplant glomerulitis is the T cell, unlike acute rejection with peritubular
      capillary C4d deposition, in which the predominant infiltrating glomerular cell
      is the monocyte.

PMID- 15957139
TI  - Steroid-responsive idiopathic glomerular capillary endotheliosis: case report and
      literature review.
AB  - Glomerular capillary endotheliosis is a lesion of endothelial cell injury.
      Morphological characteristics are endothelial swelling with glomerular
      hypertrophy and a reduction in capillary lumen size. This lesion commonly is
      found in patients with thrombotic microangiopathy, but similar histopathologic
      characteristics have been reported in patients with other diseases. A previously
      healthy 39-year-old woman presented with progressive lower-extremity swelling and
      arthralgias for 1 week. She had no other symptoms and denied prior illness. Her
      examination was remarkable for hypertension and pitting edema. Urine showed
      dysmorphic red blood cells and proteinuria. Serum creatinine level increased from
      1.1 to 2.0 mg/dL (97 to 177 micromol/L) during several weeks. She did not meet
      criteria for systemic lupus erythematosus. Other test results included a negative
      pregnancy test and normal complement levels. Additional workup was negative for
      other causes of glomerular capillary endotheliosis. She underwent 2 renal
      biopsies. The first showed marked endothelial cell swelling, and the second
      biopsy 2 months later showed disease progression. Both were consistent with
      glomerular capillary endotheliosis. Proteinuria and serum creatinine level
      elevation responded to methylprednisolone therapy within 1 week, recurred after
      steroid doses were tapered, and responded again after restarting steroid therapy
      with monthly cyclophosphamide infusions. The differential diagnosis for
      glomerular capillary endotheliosis is limited. Various causes have been
      implicated, such as dysregulation of vascular endothelial growth factor, abnormal
      collagen production, and endothelial abnormalities. We did not identify prior
      cases of idiopathic glomerular capillary endotheliosis in the literature.
      Idiopathic glomerular capillary endotheliosis may be a newly recognized entity
      potentially responsive to steroid and cytotoxic regimens.

PMID- 15957140
TI  - Detection of proximal tubular motile cilia in a patient with renal sarcoidosis
      associated with hypercalcemia.
AB  - In a normal human kidney, almost every cell type gives rise to a solitary primary
      cilium, an apical hair like nonmotile organelle that recently was linked to the
      pathogenesis of polycystic kidney disease. Motile cilia normally are not
      expressed by renal tubular cells in the mammalian kidney. Here, we report the
      unexpected detection of motile cilia arising from proximal tubular cells in a
      patient with sarcoidosis associated with hypercalcemia and renal impairment. The
      possible significance of this unusual finding is discussed.

PMID- 15957141
TI  - Novel familial WT1 read-through mutation associated with Wilms tumor and slow
      progressive nephropathy.
AB  - Wilms tumor gene 1 (WT1) is essential for normal urogenital development.
      Mutations in WT1 are involved in Wilms tumorigenesis and several associated
      syndromes, such as Denys-Drash, Frasier, or Wilms tumor, aniridia, genitourinary
      anomalies, and mental retardation syndrome. We report a novel familial WT1 point
      mutation in the stop codon of exon 10 (1730A/G; X450W) in 3 members of 1 family.
      The index patient is a 22-year-old woman in whom Wilms tumor and ureter duplex
      were diagnosed at the age of 9 years and who subsequently developed slow
      progressive nephropathy. Her mother also had late-onset nephropathy that led to
      end-stage renal failure, whereas renal function in 1 brother of the index patient
      was not impaired. We hypothesize that this type of mutation (read-through), which
      leads to an elongated, but otherwise unchanged, WT1 protein, may be associated
      with incomplete penetrance and a relatively late onset of both Wilms tumor and
      nephropathy in this family.

PMID- 15957142
TI  - Clinical pharmacists as multidisciplinary health care providers in the management
      of CKD: a joint opinion by the Nephrology and Ambulatory Care Practice and
      Research Networks of the American College of Clinical Pharmacy.

PMID- 15957143
TI  - Vitamin D deficiency in CKD: why should we care?

PMID- 15957144
TI  - Hemodialysis complications.

PMID- 15957145
TI  - A rare cause of posttransplantation nephrotic syndrome.

PMID- 15957146
TI  - Renal replacement therapies for acute renal failure: does dose matter?

PMID- 15957148
TI  - Continuous cycling peritoneal dialysis versus CAPD peritonitis rates:
      statistically or clinically significant differences?

PMID- 15957152
TI  - Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular
      pathology in characterization of an entity.
AB  - Immunohistochemical analysis of E-cadherin has changed the way lobular neoplasia
      is perceived. It has helped to classify difficult cases of carcinoma in situ with
      indeterminate features and led to the identification of new variants of lobular
      carcinoma. Pleomorphic lobular carcinoma (PLC) and pleomorphic lobular carcinoma
      in situ (PLCIS), recently described variants of invasive and in situ classic
      lobular carcinoma, are reported to be associated with more aggressive clinical
      behaviour. Although PLC/PLCIS show morphological features of classic lobular
      neoplasia and lack E-cadherin expression, it is still unclear whether these
      lesions evolve through the same genetic pathway as lobular carcinomas or are high
      grade ductal neoplasms that have lost E-cadherin. Here we have analysed a case of
      extensive PLCIS and invasive PLC associated with areas of E-cadherin-negative
      carcinoma in situ with indeterminate features, using immunohistochemistry,
      chromogenic in situ hybridization, high-resolution comparative genomic
      hybridization (CGH) and array-based CGH. We observed that all lesions lacked E
      cadherin and beta-catenin and showed gain of 1q and loss of 16q, features that
      are typical of lobular carcinomas but are not seen in high-grade ductal lesions.
      In addition, amplifications of c-myc and HER2 were detected in the pleomorphic
      components, which may account for the high-grade features in this case and the
      reported aggressive clinical behaviour of these lesions. Taken together, these
      data suggest that at least some PLCs may evolve from the same precursor or
      through the same genetic pathway as classic lobular carcinomas.

PMID- 15957153
TI  - Antipsychotic drug use: McLean Hospital, 2002.
AB  - OBJECTIVE: Major changes in antipsychotic treatment in recent years encouraged a
      survey of inpatient practice in 2002, compared with earlier samples. METHODS:
      Based on records of a random sample of McLean Hospital inpatients prescribed
      antipsychotics in 2002, the study recorded DSM-IV discharge diagnosis, all
      psychotropic treatments and doses, initial, peak and final doses of all
      antipsychotics, clinical status at admission and discharge, and adverse effects
      reported. Results were compared with similar data from our earlier surveys.
      RESULTS: Subjects were 344 inpatients (n = 202 women, 59%), diagnosed with
      psychotic (n = 102, 30%), bipolar (n = 93, 27%), major depressive (n = 67,
      19.5%), dementia (n = 19, 5.5%), substance-use (n = 28, 8%) or other psychiatric
      disorders (n = 35, 10%). Second-generation antipsychotics accounted for 88% of
      antipsychotic prescriptions; 17% of patients received > or = 2 antipsychotics and
      total CPZ-eq discharge does in 2002 averaged 291 +/- 305 mg/day (22% less than a
      1998 peak). Doses were unrelated to age, but higher in men, among psychotic vs
      major affective disorder patients, and with greater illness-severity and longer
      hospitalization. There was a 3.3-fold increase in the simultaneous use of > or =
      3 psychotropic agents since 1998. CONCLUSIONS: The use of second-generation
      antipsychotics dominates current inpatient practice. Total antipsychotic dosing
      has not increased recently, but the use of multiple psychotropics increased
      strikingly from 1998 to 2002.

PMID- 15957154
TI  - Rice proteomics: a cornerstone for cereal food crop proteomes.
AB  - Proteomics-a systematic study of proteins present in a cell, tissue, organ, or
      organism at a particular moment during the life cycle-that began with classical
      two-dimensional electrophoresis and its advancement during the 1990s, has been
      revolutionized by a series of tremendous technological developments in mass
      spectrometry (MS), a core technology. Proteomics is exerting its influence on
      biological function of genes and genomes in the era (21st century) of functional
      genomics, and for this reason yeast, bacterial, and mammalian systems are the
      best examples. Although plant proteomics is still in its infancy, evolving
      proteomic technologies and the availability of the genome sequences of
      Arabidopsis thaliana (L.) Heyhn, and rice (Oryza sativa L.), model
      dicotyledoneous and monocotyledoneous (monocot) species, respectively, are
      propelling it towards new heights, as evidenced by the rapid spurt in worldwide
      plant proteome research. Rice, with an immense socio-economic impact on human
      civilization, is a representative model of cereal food crops, and we consider it
      as a cornerstone for functional genomics of cereal plants. In this review, we
      look at the history and the current state of monocot proteomes, including barley,
      maize, and wheat, with a central focus on rice, which has the most extensive
      proteomic coverage to date. On one side, we highlight advances in technologies
      that have generated enormous amount of interest in plant proteomics, and the
      other side summarizes the achievements made towards establishing proteomes during
      plant growth & development and challenge to environmental factors, including
      disease, and for studying genetic relationships. In light of what we have learned
      from the proteomic journey in rice and other monocots, we finally reveal and
      assess their impact in our continuous strive towards completion of their full
      proteomes.

PMID- 15957155
TI  - Buprenorphine mortality, seizures and prescription data in the UK, 1980-2002.
AB  - Buprenorphine safety in overdose has been debated recently, but no mortality data
      related to this compound from the UK have been published. To gather together all
      of the buprenorphine mortality figures, a number of different sources have been
      checked. To inform on buprenorphine safety issues, accessible information related
      to its availability indicators (i.e. prescriptions; seizures) data for the 1980
      2002 time frame have been sought. In the UK, during this period, buprenorphine
      was mentioned in 43 fatalities. Typically, victims were males in the 25-44 age
      group. In 12 cases (28% of total), a verdict of suicide was given. Buprenorphine
      was detected on its own in seven cases; more frequently, it was found together
      with benzodiazepines and other opiates. Large quantities of buprenorphine were
      prescribed both in England in 1985-1989 and in 1991-1992 in Scotland, where
      seizures reached their highest levels. Buprenorphine prescriptions seemed to peak
      again after 1999, when high dose buprenorphine formulations entered the UK
      market. No positive correlation was found between the number of buprenorphine
      deaths over the years and either buprenorphine dispensings/prescriptions or
      seizures. However, an increase in buprenorphine-related deaths since 1999 was
      identified and this may be an issue which should be carefully monitored over the
      next few years.

PMID- 15957156
TI  - Investigations with cultured human microglia on pathogenic mechanisms of
      Alzheimer's disease and other neurodegenerative diseases.
AB  - Inflammation-mediated mechanisms for human neurodegenerative diseases such as
      Alzheimer's disease (AD) and Parkinson's disease (PD) have evolved from being on
      the fringe of medical hypotheses to mainstream thinking. Pioneering
      immunopathology studies with human brain tissues identified microglia associated
      with neuropathologic hallmarks of these diseases. As activated macrophages were
      known to produce many potential toxic products, this gave rise to the hypothesis
      that activated microglia (brain resident macrophages) could be contributing to
      the degeneration of key target neurons in these diseases, as well as potential
      vascular dysfunction. Studies with microglia derived from different sources,
      including human brains, have confirmed that activated microglia can mediate
      neuronal cell death. Based on these theories, a number of human clinical trials
      with antiinflammatory agents have been carried out on AD patients. Results to
      date have indicated a lack of effectiveness at slowing disease progression and
      have begun to cast doubt on the significance of inflammation in AD. It has been
      shown recently that activating microglia through immunization of amyloid plaque
      developing mice with amyloid beta peptide (Abeta) has promise as a therapeutic
      strategy and despite some setbacks, has potential as a treatment for AD patients.
      This article will consider experimental data with microglia to determine whether
      the additional targets need to be investigated. The use of human microglia
      cultures, in particular those derived from elderly diseased human brains, offers
      an experimental system that can closely model the cell type activated in human
      neurodegenerative diseases. Experimental data produced by our laboratory and
      others is reviewed to determine the contribution of this unique experimental
      model to understanding disease mechanisms and possibly discovering new
      therapeutic targets.

PMID- 15957157
TI  - Elevation of intracellular Ca2+ modulates A-currents in rat cerebellar granule
      neurons.
AB  - In the brain, the transient-inactivating voltage-gated potassium channel currents
      (called I(K(A)) or A-currents) are activated at subthreshold membrane potentials
      to control the excitability of neurons. In the current study, the effect of
      intracellular calcium on the A-current and the action mechanism of intracellular
      calcium was investigated by using the whole-cell voltage-clamp technique.
      Elevation of intracellular calcium by addition of 2 mM CaCl2 in the pipette
      solution significantly modulated both the peak amplitude and the kinetics of the
      A-current in rat granule neurons. The peak amplitudes of the A-current were 1,060
      +/- 87 pA and 1,972 +/- 16 pA under conditions of no Ca2+ and elevated
      intracellular Ca2+, respectively. The time to peak, the time course of fast
      inactivation, and the steady-state inactivation property of the A-current were
      all significantly altered by elevating the intracellular Ca2+. Replacement of the
      Ca2+ in the pipette solution with the same concentration of Co2+ did not mimic
      the effects of intracellular Ca2+ on the A-current amplitude and kinetics. These
      effects are similar to the behavior of the reconstituted Kv4/KChIP (K(V) channel
      interacting proteins) current induced by expression of KChIP and Kv4 together in
      a cell expression system. Application of 10 microM arachidonic acid, which can
      bind to the Kv4/KChIP complex, inhibited the A-current and eliminated the effects
      of intracellular Ca2+ on the A-current, suggesting that KChIP may be involved in
      the effects of Ca2+ on the A-current. Collectively, our results indicate that
      elevated intracellular Ca2+ modulates the amplitude, fast activation, and steady
      state inactivation characteristics of the A-current in rat cerebellar granule
      neurons, and this may occur via KChIP.

PMID- 15957158
TI  - Case reports of oculofaciocardiodental syndrome with unusual dental findings.
AB  - We report on two new cases of oculofaciocardiodental (OFCD) syndrome
      characterized by cataracts, microphthalmia, facial anomalies, cleft palate,
      cardiac septal defects, and canine radiculomegaly. We also review previous
      patients. The syndrome is caused by mutations in the BCOR gene, which maps to
      Xp11.4. Mutational analysis in one of our patients showed a deletion of a single
      nucleotide, c.2613delC, predicting a novel frameshift mutation with a premature
      stop codon, p.F871Lfs8X.

PMID- 15957159
TI  - Three cases with de novo 6q imbalance and variable prenatal phenotype.
AB  - We describe two families in which three fetuses had a de novo 6q imbalance and
      abnormal phenotypes. We determined the boundaries and the parental origin of the
      chromosomal alterations by segregation analysis using a panel of short tandem
      repeats (STRs) located on 6q. Cases 1 and 2 (family A) were two sibs with 6q
      imbalance involving different regions. Case 1 was a female fetus with
      arthrogryposis, who had a complex rearrangement resulting in two deleted regions
      (6q22 and 6q25.1-q25.2) and a duplication of 6q23-q25.1. This latter imbalance
      was reported previously and is associated with joint contractures and short neck,
      also present in this fetus. The sib (case 2) had intrauterine growth restriction
      (IUGR) and agenesis of the ductus venosus. This male died shortly after birth;
      postnatal karyotype and molecular investigations showed a 6q21 de novo deletion.
      Case 3 (family B) had a prenatally detected deletion of 6q14-q16. Autopsy of the
      fetus documented minor facial anomalies and contractures of the limbs. All
      rearrangements were de novo and of paternal origin. Our data and the consistent
      number of cases of de novo 6q alterations previously reported suggest that
      chromosome arm 6q could be prone to rearrangements resulting in heterogeneous
      phenotypes. In family A, chromosome 6q imbalances involving different chromosomal
      regions were present in two consecutive pregnancies. In such cases counseling
      should suggest the impossibility of excluding recurrence of a chromosomal
      imbalance, and should discuss the option of early prenatal diagnosis in
      subsequent pregnancies.

PMID- 15957160
TI  - Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated.
AB  - Uniparental disomy (UPD) describes the inheritance of a pair of chromosomes from
      only one parent. The concept was introduced in Medical Genetics by Engel (1980);
      Am J Med Genet 6:137-143. Aside UPD 15, which is the most frequent one, up to now
      (February 2005) 197 cases with whole chromosome maternal UPD other than 15 (124 X
      heterodisomy, 59 X isodisomy, and 14 cases without information of the mode of
      UPD) and 68 cases with whole chromosome paternal UPD other than 15 (13 X
      heterdisomy, 53 X isodisomy, and 2 cases without information of the mode of UPD)
      have been reported. In this review we discuss briefly the problems associated
      with UPD and provide a comprehensive clinical summary with a bibliography for
      each UPD other than 15 as a guide for genetic counseling.

PMID- 15957161
TI  - Farnesylthiosalicylic acid blocks mammalian target of rapamycin signaling in
      breast cancer cells.
AB  - Estradiol (E2) stimulates proliferation of hormone-dependent breast cancer and
      exerts downstream effects on growth factors and their receptors. Key among the
      pathways' mediating growth factor action is the MAP kinase signaling cascade and
      the PI-3 kinase pathway with its downstream effector mTOR. We postulated that
      farnesylthiosalicylic acid (FTS), a novel anti-Ras drug, could effectively
      inhibit hormone-dependent breast cancer because Ras activates both the MAP kinase
      and the PI3 kinase pathways. Wild-type MCF-7 cells and a long-term estrogen
      deprived subline (LTED) were used to examine the effect of FTS on cell growth and
      on several biochemical parameters. FTS inhibited growth of both cell lines by
      reducing proliferation and inducing apoptosis. These effects correlated best with
      blockade of phosphorylation of PHAS-I and p70 S6 kinase, 2 downstream effectors
      of mTOR. We observed only minimal inhibition of Akt, an effector upstream of
      mTOR. Taken together, these findings demonstrate a novel effect of FTS to inhibit
      mTOR signaling and also suggest that mTOR has a key role in breast cancer cell
      proliferation. Unexpectedly, only minimal inhibition of MAP kinase occurred in
      response to FTS at concentrations that markedly reduced cell growth. These later
      data provide support for the concept that FTS exerts its effects predominantly by
      blocking mTOR and to a lesser effect by inhibition of MAP kinase in breast cancer
      cells.

PMID- 15957162
TI  - Intrapulmonary solitary fibrous tumor in an eight-year-old male.
AB  - We describe an 8-year-old male who had an intrapulmonary solitary fibrous tumor
      (SFT). SFTs of the pleura are now thought to originate from subpleural
      mesenchymal cells, and a pathological diagnosis is obtained by a specific marker,
      i.e., CD34 expression on the tumor cells. The SFT reported here is an extremely
      rare phenotype in two respects: it originated in a child under age 10 years, and
      it expanded in an intrapulmonary fashion.

PMID- 15957163
TI  - Association of a single nucleotide polymorphism in the matrix metalloproteinase-1
      promoter with glioblastoma.
AB  - A key feature in the malignant behavior of glioblastoma is the tendency to invade
      host brain tissue surrounding the primary tumor site. Several members of the
      matrix metalloproteinase family are thought to contribute to this invasive
      capacity. A single nucleotide polymorphism has been described in the matrix
      metalloproteinase-1 (MMP-1) promoter that consists of either the presence or
      absence of a guanine nucleotide at position -1607. The presence of the guanine
      base creates a functional binding site for members of the ETS family of
      transcription factors and has been shown to increase MMP-1 transcription. The
      purpose of our study was to characterize this polymorphism in human glioblastoma.
      Promoter genotyping was performed on brain tumor tissue obtained from 81 patients
      and compared to 57 healthy individuals. The 2G/2G genotype is more prevalent in
      glioblastoma tissue compared to healthy individuals (p = 0.01). mRNA and protein
      expression were measured in a subset of brain tumor and normal brain tissue
      samples. MMP-1 protein levels are significantly higher in glioblastoma tissue
      compared to normal brain (p = 0.001). Electromobility shift assays and promoter
      assays were performed to assess binding capability and transcriptional activity,
      respectively. Proteins present in glioma cell lines can specifically bind the 2G
      promoter probe. MMP-1 transcription is significantly higher in cells transfected
      with the 2G promoter when compared to cells transfected with the 1G promoter
      (p<0.02). This polymorphism may provide a mechanism for increased expression of
      MMP-1 in malignant gliomas via elevation of MMP-1 mRNA transcription and may
      underlie the invasive phenotype.

PMID- 15957164
TI  - High constant incidence rates of second cutaneous melanomas.
AB  - The incidence of most epithelial cancers rises with a power of age. However,
      second breast cancers have a high constant incidence independent of age. The skin
      is one of the few other sites allowing examination of age incidence curves of
      second neoplasms of the same organ. We considered the risk of second primary
      cutaneous malignant melanoma (CMM) in a population-based series of 3,439 first
      CMM registered and followed-up between 1974 and 2003 in the Swiss Cantons of Vaud
      and Neuchatel (about 786,000 inhabitants). A total of 43 cases of second CMM were
      observed vs. 9.3 expected, corresponding to a standardized incidence ratio (SIR)
      of 4.6. The SIR was 8.5 under age 50, 5.7 at age 50-59 and 3.5 at age 60 or over.
      At 20 years, the cumulative risk of second CMM was 5%. Age-specific incidence
      rates of second primary CMM did not vary across age groups 30-39 through 80+,
      ranging between 1 and 2.5 per 1,000 person-years. Thus, the risk of CMM is
      substantially increased in subjects diagnosed with a CMM, and the relative risk
      is greater at younger age and declines with advancing age. The high constant
      incidence curve of second CMM is compatible with the occurrence of a single
      mutational event in a population of susceptible individuals.

PMID- 15957165
TI  - Tumor type M2 pyruvate kinase (TuM2-PK) as a novel plasma tumor marker in
      melanoma.
AB  - Proliferating cells express the pyruvate kinase isoenzyme type M2 (M2-PK). This
      enzyme exists as an active tetramer and an inactive dimer. The dimeric form is
      predominantly found in tumor cells and is therefore termed Tumor M2-PK (TuM2-PK).
      TuM2-PK molecules are released into the peripheral blood and may hereby function
      as a marker of tumor load in cancer patients. Our study was aimed to investigate
      TuM2-PK as a potential plasma marker in melanoma patients compared to the well
      established serum marker S100beta. We measured the concentration of TuM2-PK in
      plasma and S100beta in corresponding serum samples from 300 melanoma patients and
      53 healthy controls using a sandwich ELISA and an immunoluminometric assay,
      respectively. Plasma concentrations of TuM2-PK were significantly increased in
      melanoma patients compared to healthy controls (9.30 U/ml vs. 7.20 U/ml; p =
      0.0036) and correlated with tumor load (p < 0.0005) and disease stage (p <
      0.0005). Patients with elevated plasma TuM2-PK (cut-off = 15 U/ml) presented a
      reduced overall (p < 0.000005) and progression-free (p = 0.023) survival.
      Multivariate analysis revealed plasma TuM2-PK and serum S100beta as independent
      predictors of overall survival in metastasized patients. Neither plasma TuM2-PK
      nor serum S100beta showed prognostic relevance for tumor-free patients. Although
      the sensitivity and specificity to predict disease progression or death was
      higher for serum S100beta compared to plasma TuM2-PK, the combination of both
      markers improved the estimation of prognosis compared to that of serum S100beta
      alone.

PMID- 15957166
TI  - Expression of Com-1/P8 in human breast cancer and its relevance to clinical
      outcome and ER status.
AB  - Com-1 is a recently discovered molecule that has putative action on the
      metastatic nature of cancer cells. The molecular action and clinical implication
      in cancer and prognosis are yet to be established. The current study examined the
      role of Com-1 in a cohort of patients with breast cancer, with particular
      emphasis on its relationship with clinical outcomes and ER status. A panel of
      human breast cancer cell lines were tested. A cohort of breast cancer tumours (n
      120) with matched normal non-neoplastic mammary tissues (n = 32) were used.
      Expression of Com-1 in cancer cells and mammary tissues were studied using
      conventional and real-time quantitative PCR. Expression profile was analysed
      against clinical information including tumour grade, staging, nodal status, ER
      status and survival of the patients. Statistical analysis was Mann-Whitney U-test
      and Cox Proportion analysis. Com-1 was expressed in breast cancer cell lines. Com
      1 protein staining was primarily found in nucleus of epithelial cells of mammary
      tissues. Tumour cells in breast tissues exhibited a significant reduction in
      nuclear staining of Com-1, compared to normal epithelial cells (p = 0.0061).
      Breast tumour tissues expressed similar levels of Com-1, compared to normal non
      neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in
      tumours from patients with predicted good, moderate, to poor prognosis (using
      Nottingham Prognostic Index) (166 +/- 135 copies of Com1 transcript, 44.3 +/- 36
      and 0.64 +/- 0.24, respectively, p = 0.06 by Kruskal-Wallis test). Likewise, node
      positive tumours had low levels of Com-1, compared to node negative tumours.
      Tumours from patients who developed metastasis (11.4 +/- 7 copies of Com1
      transcript), had local recurrence (41.5 +/- 3.7 copies of Com1 transcript), or
      who died of breast cancer (0.058 +/- 0.03 copies of Com1 transcript) had lower
      levels of Com-1, when compared to tumours from patients who remained disease free
      (156 +/- 129 copies of Com1 transcript). There was no significant correlation
      between Com-1 and overall survival or disease free survival. When ER status were
      taken into consideration, it was demonstrated that low levels of Com-1 in ER-beta
      positive tumours were highly correlated with shorter overall survival of the
      patients (p = 0.018) (median follow-up 120 months). Com-1 is a nuclear protein,
      whose expression is reduced in human breast cancer tissues and cancer cell lines.
      The loss of Com-1 protein is primarily from the nuclear compartment in cancer
      cells. The expression levels of Com-1 in breast tumours are correlated with the
      prognosis of the patients and with the long term overall survival in association
      with ER status.

PMID- 15957167
TI  - Different impact from betel quid, alcohol and cigarette: risk factors for
      pharyngeal and laryngeal cancer.
AB  - The risks of betel quid chewing with or without tobacco, alcohol drinking and
      cigarette smoking have been well explored in the oral cavity but not in the
      pharynx and larynx. We conducted a case-control study to investigate the
      association of these three risk factors to cancers of the pharynx and larynx in
      Taiwan. A total cases of 148 pharyngeal cancer, 128 laryngeal cancer and 255
      hospital controls, all men, were recruited. Betel quid chewing was a significant
      independent risk factor (adjusted odds ratio [aOR] = 7.7; 95% confidence interval
      [CI] = 4.1-15.0) similar to that of alcohol drinking (aOR = 6.6; 95% CI = 3.5
      13.0) for pharyngeal cancer, but not for laryngeal cancer (aOR = 1.3; 95% CI =
      0.7-2.5) on which cigarette smoking (aOR = 7.1) exerts a stronger significant
      independent risk than alcohol drinking (aOR = 3.8). For pharyngeal cancers,
      chewers who consumed >20 quid/day, chewed with inflorescence in the quid or
      swallowed the betel quid juice were at higher risks; significant dose-response
      effects were found in daily quantity of drinking and chewing, and cumulative
      quantity of drinking. Synergistic effects from the 3 risk factors existed both on
      the pharynx (aOR = 96.9) and the larynx (aOR = 40.3), and attributed for 93.1%
      and 92.9% respectively. Our study is the first evidence to show that betel quid
      chewing without tobacco has different impact on the pharynx (digestive tract) and
      the larynx (airway), and supports the concept that exposure quantity and direct
      mucosal contact with the betel quid juice may contribute to carcinogenesis. Our
      results show an important insight into the impact of betel quid chewing on other
      sites of the digestive tract other than the oral cavity.

PMID- 15957168
TI  - Role for casein kinase 2 in the regulation of HIF-1 activity.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that
      plays a major role in cellular adaptation to hypoxia. The mechanisms regulating
      HIF-1 activity occurs at multiple levels in vivo. The HIF-1alpha subunit is
      highly sensible to oxygen and is rapidly degraded by the proteasome 26S in
      normoxia. Activation in hypoxia occurs through a multistep process including
      inhibition of HIF-1alpha degradation, but also increase in the transactivation
      activity of HIF-1. Several data indicate that phosphorylation could play a role
      in this regulation. In this report, we investigated the role of casein kinase 2
      (CK2), an ubiquitous serine/threonine kinase, in the regulation of HIF-1
      activity. Hypoxia was capable of increasing the expression of the beta subunit of
      CK2, of inducing a relocalization of this subunit at the plasma membrane, of
      inducing nuclear translocation of the alpha subunit and of increasing CK2
      activity. Three inhibitors of this kinase, DRB (5,6-dichloro-1-beta-D
      ribofuranosyl-benzimidazole), TBB (4,5,6,7-tetrabromotriazole) and apigenin, as
      well as overexpression of a partial dominant negative mutant of CK2alpha, were
      shown to inhibit HIF-1 activity as measured by a reporter assay and through
      hypoxia-induced VEGF and aldolase expression. This does not occur at the
      stabilization process since they did not affect HIF-1alpha protein level. DNA
      binding activity was also not inhibited. We conclude that CK2 is an important
      regulator of HIF-1 transcriptional activity but the mechanism of this regulation
      remains to be determined. Since HIF-1 plays a major role in tumor angiogenesis
      and since CK2 has been described to be overexpressed in tumor cells, this new
      pathway of regulation can be one more way for tumor cells to survive.

PMID- 15957169
TI  - Genetic and environmental determinants of risk for cholangiocarcinoma via
      Opisthorchis viverrini in a densely infested area in Nakhon Phanom, northeast
      Thailand.
AB  - Infection with Opisthorchis viverrini (OV) is associated with cholangiocarcinoma.
      OV is common in northeast Thailand, but less than 10% of the inhabitants develop
      cholangiocarcinoma. Animal experiments suggest that OV infection alone does not
      cause cholangiocarcinoma, and thus other environmental and genetic factors may
      play a role in causation. We conducted a population-based case-control study in
      which sex, age and place of residence were matched individually. Polymorphisms of
      GSTM1 and GSTT1 alone were not associated with risk for cholangiocarcinoma, while
      an elevated level of antibodies against OV (ELISA) > or = 0.200 was the strongest
      risk indicator (odds ratio as compared to that <0.200 = 27.09 [95% confidence
      interval (CI): 6.30-116.57]. Compared to subjects who had a normal antibody range
      and the wild-type GSTM1 gene, those who had elevated antibodies had higher odds
      ratios of 10.34 (95% CI: 1.31-81.63) [corrected] for wild-type GSTM1 and 18.00
      (95% CI: 3.33-97.40) [corrected] for the null variant thereof, respectively. Past
      and current regular drinkers of alcohol had higher risk [odds ratio = 5.39 (95%
      CI: 1.11-26.06) and 4.82 (95% CI: 1.29-18.06), respectively]. Eating fermented
      products was an independent risk factor. Smokers or consumers of fermented fish
      had substantially increased risk if they were past or current drinkers. Infection
      with OV correlates strongly with cholangiocarcinoma, susceptibility to which may
      be possibly associated with GSTM1 polymorphism. Alcohol may affect metabolic
      pathways of endogenous and exogenous nitrosamines.

PMID- 15957170
TI  - Alcohol consumption and risk of renal cell carcinoma: a prospective study of
      Swedish women.
AB  - Previous literature, although not consistent, suggests that moderate alcohol
      consumption might be associated with decreased risk of renal cell carcinoma (RCC)
      in women. Thus, we examined the association between alcohol intake and the
      incidence of RCC by analyzing data from the Swedish Mammography Cohort, a
      population-based prospective cohort of 59,237 women, aged 40-76 years, who, at
      baseline in 1987-1990, were cancer free and had completed a food-frequency
      questionnaire including questions about alcohol consumption. Through June 30,
      2004, 132 incident cases of RCC were diagnosed. We used the Cox proportional
      hazards model to estimate age and body mass index (BMI) adjusted rate ratios
      (RRs) and their 95% confidence intervals (CIs). Women who consumed >4.3 grams per
      day of alcohol (ethanol) had nonsignificantly lower risk of RCC than did women
      who consumed <2.5 g/d (RR = 0.71, 95% CI 0.42-1.19); among women > or = 55 years
      of age at entry into the cohort, corresponding risk estimates were RR = 0.33, 95%
      CI 0.10-1.05, p for trend = 0.04 and among women with BMI >25 kg/m2, RR = 0.30,
      95% CI 0.09-0.97, p for trend = 0.04. Consistent with these findings, women who
      drank 1 or more servings of total alcoholic beverages per week had lower RCC risk
      than did women who drank less (RR = 0.62, 95% CI 0.41-0.94); the corresponding
      estimate for women > or = 55 years of age was RR = 0.44, 95% CI 0.22-0.88.
      Results from our prospective cohort study of middle-aged and elderly women
      indicate that moderate alcohol consumption may be associated with decreased risk
      of RCC.

PMID- 15957171
TI  - Use of nonaspirin NSAIDs and risk of lung cancer.
AB  - Epidemiologic evidence is conflicting regarding the potential for nonsteroidal
      antiinflammatory drugs (NSAIDs) to lower the risk of lung cancer. We thus
      determined the incidence of lung cancer among a cohort of over 242,000 adults in
      Denmark who had been issued NSAID prescriptions during 1991-2002 and calculated
      the relative risks of this cancer according to the numbers of prescriptions
      received. Similar analyses were conducted among a subset with chronic obstructive
      pulmonary disease, of whom the large majority was assumed to have been smokers,
      as an indirect control for smoking. Utilization of Danish registries ensured
      essentially complete and unbiased ascertainment of prescriptions and cancer
      outcomes. The relative risks of lung cancer among NSAID users redeeming 10 or
      more prescriptions vs. nonusers in the general population and among chronic
      obstructive pulmonary disease patients were 1.51 (95% CI = 1.33-1.71) and 1.55
      (95% CI = 0.93-2.60) and tended to decline with decreasing numbers of NSAIDs
      prescribed. Separate analyses for adenocarcinoma and squamous cell carcinoma also
      failed to show reduced risks among NSAID users. Confounding by indication may
      have contributed to the increased risks, but the study provides no evidence to
      suggest that recent NSAID intake may be protective for lung cancer.

PMID- 15957172
TI  - Increased incidence of invasive breast cancer after the introduction of service
      screening with mammography in Sweden.
AB  - Screening with mammography has been shown to substantially reduce mortality from
      breast cancer. The incidence of invasive cancer will increase as screening
      starts, and it is desirable that it gradually returns to the same level as before
      screening. Age-specific incidence of invasive breast cancer in 11 Swedish
      counties, including 463,000 women aged 40-74 years, was analysed before and after
      the start of service screening with mammography. Incidence, as observed on
      average during 12.8 years from screening start, was compared to expected
      incidence based on the incidence during a 15-year period preceding screening
      start. The height of the incidence peak during the first screening round was
      increasing with increasing age, compatible with the accumulation in the
      population of slowly growing tumours by age. All analysed age groups showed an
      increased ratio between observed stabilised incidence 7-14 years after screening
      start and expected incidence. When relative risks were adjusted for lead time,
      the estimates were 1.54 (95% confidence interval [CI] 1.33-1.79) and 1.21 (95% CI
      1.04-1.41) for the age groups 50-59 and 60-69 years, respectively. In the age
      groups 40-49 and 70-74, no change was observed. The findings were further
      confirmed by the observation of a disappearance in the screened population of the
      notch in the increasing trend of age-specific breast cancer incidence for the
      ages after menopause. This notch could indicate hormone-related retardation in
      tumour growth around menopause. It appears that many of these clinically
      insignificant, retarded tumours are detected with screening mammography.

PMID- 15957173
TI  - Activating mutations in the extracellular domain of the melanoma inducing
      receptor Xmrk are tumorigenic in vivo.
AB  - Mutated versions or overexpression of receptor tyrosine kinases such as the
      epidermal growth factor receptor are found frequently in various cancers. In
      Xiphophorus the formation of hereditary melanoma is caused by the overexpression
      of the Xmrk oncogene locus. Xmrk is a mutationally altered version of the
      epidermal growth factor receptor. Two amino acid changes in the extracellular
      domain of the receptor were shown in vitro to be responsible for a constitutive,
      ligand-independent activity of Xmrk. To analyze whether these two mutations are
      indeed responsible for the in vivo oncogenic activity of the receptor, both were
      independently introduced into the wild-type, non-oncogenic Xiphophorus EGF
      receptor and tested in Medaka embryos for their tumorigenic capacity. Both
      mutations were sufficient to induce tumors after short latency periods and at a
      comparable frequency as the native Xmrk oncogene. The G359R mutation led to a
      significantly higher tumor rate than the C578S mutation. Our study shows that
      subtle point mutations of the EGF-receptor can lead to a highly tumorigenic
      oncoprotein.

PMID- 15957174
TI  - Risk of cervical cancer in women with a family history of breast and female
      genital tract neoplasms.

PMID- 15957175
TI  - Anti-inflammatory effect of albuterol enantiomers during respiratory syncytial
      virus infection in rats.
AB  - Every year in the United States, respiratory syncytial virus (RSV) infections in
      infants and young children cause more than 120,000 hospitalizations, often
      complicated by the need for mechanical ventilation; yet no effective therapy is
      currently available for this disease. We showed previously that RSV infection is
      associated with neurogenic inflammation in the lower respiratory tract. In the
      present study, we sought to determine whether aerosolized beta(2)-receptor
      agonists inhibit neurogenic-mediated albumin extravasation in the airways of RSV
      infected, mechanically ventilated rats, and to compare the anti-inflammatory
      effects of racemic albuterol ((RS)-albuterol) to its individual enantiomeric
      components (R)-albuterol and (S)-albuterol. Albumin extravasation evoked by
      sensorineural stimulation with capsaicin was inhibited only partially by 0.63 mg
      (RS)-albuterol, and higher doses had minimal incremental effects. In contrast,
      the anti-inflammatory effect of (R)-albuterol was already larger at the lowest
      dose of 0.31 mg, and complete inhibition of neurogenic exudation was observed at
      higher doses. (S)-albuterol had no significant inhibitory effect up to 1.25 mg,
      and had only partial inhibitory effect at higher doses. The anti-inflammatory
      effect of (R)-albuterol was independent from the expression of substance P
      neurokinin 1 receptors, suggesting a direct vascular effect. Our data show that
      (R)-albuterol has a much stronger inhibitory effect on neurogenic inflammation in
      RSV-infected airways when aerosolized in enantiomerically pure form, rather than
      in a racemic mixture with (S)-albuterol. Based on these data, we speculate that
      (R)-albuterol may be more effective than other adrenergic agents in the
      management of bronchiolitis.

PMID- 15957177
TI  - Analysis of human tear fluid by Fourier transform infrared spectroscopy.
AB  - The purpose of this research is to find some useful spectroscopic factors in
      human tear fluid contents to monitor diurnal changes of the physicochemical
      ocular conditions noninvasively. All tear fluid samples were collected with glass
      microcapillary tubes from both eyes of three donors and analyzed by Fourier
      transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR). We
      measured the peak intensities at 2852, 1735, 1546, and 1242 cm(-1), and the peak
      intensity ratios among those peaks in the second derivative spectra. We found
      significant diurnal and individual variations in those peak intensities for tear
      fluid obtained from right and left eyes. Among these variations, we observed
      significant changes in tear samples between right and left eyes. In this case the
      peak intensity ratio between 1242 (phosphate ester) and 2852 cm(-1) (fatty acid
      methylene) of right eye tear fluid was increased in the afternoon (1600 to 1900
      h), while that of left eye tear fluid did not change significantly. In the ratio
      between 1242 (phosphate ester) and 1546 cm(-1) (amide II), the difference was not
      observed between both eyes. We conclude that the difference in diurnal variations
      of biochemical constituents between right and left eye tear fluids could be
      monitored noninvasively and nondestructively by FTIR technique and this method
      could be useful in the future for tear diagnoses.

PMID- 15957176
TI  - Novel rearrangement of chromosome band 22q11.2 causing 22q11 microdeletion
      syndrome-like phenotype and rhabdoid tumor of the kidney.
AB  - The 22q11.2 microdeletion syndrome is the most frequent microdeletion syndrome in
      humans, yet its genetic basis is complex and is still not fully understood. Most
      patients harbor a 3-Mb deletion (typically deleted region [TDR]), but
      occasionally patients with atypical deletions, some of which do not overlap with
      each other and/or the TDR, have been described. Microduplication of the TDR leads
      to a phenotype similar, albeit not identical, to the deletion of this region.
      Here we present a child initially suspected of having 22q11 microdeletion
      syndrome, who in addition developed a fatal malignant rhabdoid tumor of the
      kidney. Detailed cytogenetic and molecular analyses revealed a complex de novo
      rearrangement of band q11 of the paternally derived chromosome 22. This
      aberration exhibited two novel features. First, a microduplication of the 22q11
      TDR was associated with an atypical 22q11 microdeletion immediately telomeric of
      the duplicated region. Second, this deletion was considerably larger than
      previously reported atypical 22q11 deletions, spanning 2.8 Mb and extending
      beyond the SMARCB1/SNF5/INI1 tumor suppressor gene, whose second allele harbored
      a somatic frameshift-causing sequence alteration in the patient's tumor. Two
      nonallelic homologous recombination events between low-copy repeats (LCRs) could
      explain the emergence of this novel and complex mutation associated with the
      phenotype of 22q11 microdeletion syndrome.

PMID- 15957178
TI  - Solution properties of (1-->3)-alpha-D-glucan and its sulfated derivative from
      Poria cocos mycelia via fermentation tank.
AB  - From Poria cocos mycelia yielded via a pilot scale facility-fermentation tank, a
      water-insoluble (1-->3)-alpha-D-glucan coded as Pi-PCM3-I was isolated by
      extraction with 0.5 M NaOH/0.01 M NaBH(4) aqueous solution. Nine fractions from
      F1 to F9 with a weight-average molecular mass (M(w)) range from 7.75 x 10(4) to
      57.3 x 10(4) were prepared from the Pi-PCM3-I sample by a nonsolvent addition
      method. The fractions were reacted with chlorosulfonic acid-pyridine complex to
      product water-soluble sulfated derivatives coded as S1 to S8 with M(w) from 2.36
      x 10(4) to 14.5 x 10(4) and degree of substitution (DS) of 0.86-1.38. M(w), z
      average radius of gyration (s(2) (z) (1/2)), the second virial coefficient
      (A(2)), and the intrinsic viscosity ([eta]) of the native and sulfated Pi-PCM3-I
      were measured by laser light scattering (LLS), size-exclusion chromatography
      combined with LLS (SEC-LLS), and viscometry at 25 degrees C. The Mark-Houwink
      equations for Pi-PCM3-I in 0.25 M LiCl/dimethylsulfoxide (DMSO) (Me(2)SO) and for
      its sulfated derivative in 0.15 M NaCl aqueous solution at 25 degrees C were
      established to be [eta] = 1.33 x 10(-2) M(w) (0.75+/-0.01) (mL g(-1)) and [eta] =
      1.46 x 10(-4) M(w) (1.13+/-0.01) (mL g(-1)), respectively. On the basis of
      theories for a wormlike cylinder model, the conformational parameters of the
      native and sulfated Pi-PCM3-I were calculated to be 760 +/- 50 and 1060 +/- 30
      nm(-1) for the molar mass per unit contour length (M(L)), 6.3 +/- 0.5 and 13.1 +/
      1 nm for the persistence length (q), and 14.9 +/- 0.2 and 31.8 +/- 1 for the
      characteristic ratio (C( proportional, variant)), respectively. The results
      revealed that Pi-PCM3-I existed as an extended flexible chain in 0.25 M
      LiCl/Me(2)SO, and its sulfated derivative existed as a semistiff chain in 0.15 M
      NaCl aqueous solution. Furthermore, Pi-PCM3-I possessed similar structure and
      molecular parameters to wc-PCM3-I from a rotary shaker; this suggests promising
      industrialization of Poria cocos polysaccharides.

PMID- 15957179
TI  - Electron pairing and chemical bonds. Electron fluctuation and pair localization
      in ELF domains.
AB  - This article reports the numerical comparison of the quantities characterizing
      the extent of electron fluctuation and pair localization in the domains
      determined by the direct minimization of electron fluctuation with the domains
      resulting from the partitioning of the molecules based on the topological
      analysis of the so-called electron localization function (ELF). Such a comparison
      demonstrates that the ELF partitioning can be regarded as a feasible alternative
      to computationally much more demanding direct optimization of minimum fluctuation
      domains. This opened the possibility of the systematic scrutiny of the electron
      pair model of the chemical bond, and as it was demonstrated, the previous
      pessimistic claims about the applicability of this model are not completely
      justified.

PMID- 15957180
TI  - Computational analyses of singlet-singlet and singlet-triplet transitions in
      mononuclear gold-capped carbon-rich conjugated complexes.
AB  - Density functional theory and CASSCF calculations have been used to determine
      equilibrium geometries and vibrational frequencies of metal-capped one
      dimensional pi-conjugated complexes (H3P)Au(C[triple chemical bond]C)(n)(Ph) (n =
      1-6), (H3P)Au(C[triple chemical bond]CC6H4)(C[triple chemical bond]CPh), and H3P-
      Au(C[triple chemical bond]CC6H4)C[triple chemical bond]CAu--PH3 in their ground
      states and selected low-lying pi(pi)* excited states. Vertical excitation
      energies for spin-allowed singlet-singlet and spin-forbidden singlet-triplet
      transitions determined by the time-dependent density functional theory show good
      agreement with available experimental observations. Calculations indicate that
      the lowest energy 3(pi(pi)*) excited state is unlikely populated by the direct
      electronic excitation, while the low-lying singlet and triplet states, slightly
      higher in energy than the lowest triplet state, are easily accessible by the
      excitation light used in experiments. A series of radiationless transitions among
      related excited states yield the lowest 3(pi(pi)*) state, which has enough long
      lifetimes to exhibit its photochemical reactivities.

PMID- 15957181
TI  - Persistent pulmonary hypertension of newborn due to congenital capillary alveolar
      dysplasia.
AB  - Congenital alveolar capillary dysplasia is a rare and fatal cause of pulmonary
      hypertension in neonates. We report on a term baby with severe pulmonary
      hypertension unresponsive to high-frequency ventilation and nitric oxide. A
      diagnosis of alveolar capillary dysplasia was established on autopsy. We review
      the literature regarding pathophysiology, clinical presentations, associated
      malformations, and treatment trials.

PMID- 15957182
TI  - Endoscopic findings in children with obstructive sleep apnea: effects of age and
      hypotonia.
AB  - Obstructive sleep apnea (OSA) syndrome is a common disorder among children and is
      often associated with significant morbidity. The causes of OSA are related to
      either fixed upper airway abnormalities such as adenotonsillar hypertrophy, or
      dynamic airway abnormalities such as laryngomalacia and pharyngeal wall collapse.
      The aim of the present study was to determine the prevalence of dynamic upper
      airway abnormalities, based on endoscopic findings, in normotonic and hypotonic
      children with polysomnographically documented OSA. The records of 39 consecutive
      children with OSA who underwent bronchoscopy (22 with normal tone, and 17 with
      hypotonia) were reviewed. The prevalence of dynamic defects among children with
      normal tone decreased with age. All 7 patients less than 1 year old had dynamic
      abnormalities (isolated or combined fixed/dynamic), compared to only 66% (6/9) of
      patients between 1-2 years old, and 17% (1/6) of children more than 2 years old.
      In contrast, dynamic abnormalities were very common among hypotonic children,
      independent of age. Since children with dynamic defects are less likely to
      respond to surgical treatments, it would be appropriate to identify these
      children prior to any intervention. Due to the higher frequency of dynamic
      defects in both infants (< 1 year) and hypotonic children, it may be appropriate
      to include endoscopy as part of the diagnostic evaluation of OSA in these
      subgroups.

PMID- 15957183
TI  - Trisomy 3q25.1-qter and monosomy 8p23.1-pter in a patient: cytogenetic and
      molecular analysis with delineation of the phenotype.
AB  - We describe a 4-year-old boy with partial 3q trisomy and distal 8p monosomy. The
      patient presented with mental retardation, dysmorphic face, congenital heart
      defect, brain and genital anomalies, and behavioral problems. The conventional
      cytogenetic analysis showed a 46,XY,add(8p) karyotype. Reverse painting and
      microsatellite analysis demonstrated a partial monosomy of 8p23.1 --> pter and a
      partial trisomy of 3q25.1 --> qter. The data suggest that the chromosomal
      rearrangement originated from a de novo translocation in a paternal germinal
      cell. The phenotype observed in our patient resulted from the combination of
      those defects described in the isolated dup(3q) and distal del(8p) syndromes.

PMID- 15957184
TI  - Comparison of lung area by chest radiograph, with estimation of lung volume by
      helium dilution during prone and supine positioning in mechanically ventilated
      preterm infants: a pilot study.
AB  - Measurement of lung volume may be useful in determining the degree of lung
      disease and for optimizing an infant's mechanical ventilator settings. A chest
      radiograph (CXR) is often used to estimate lung volume, because direct
      measurement, e.g., functional residual capacity (FRC), is neither practical nor
      possible in the neonatal intensive care unit. In supinely positioned infants,
      good correlation was found between lung area determined by CXR and lung volume,
      e.g., functional residual capacity (FRC). Whether this is true for the prone
      position is unknown. Since positioning may affect oxygenation and pulmonary
      function, we studied the relationship between lung area measured from CXR and FRC
      during both supine and prone positioning in 14 mechanically ventilated preterm
      infants. Lung area was determined from CXRs using computed radiography and FRCs
      obtained by helium dilution at end-expiration in both supine and prone positions.
      Reproducibility of lung area measurements was demonstrated by high correlations
      between two observers (R2 = 0.92 and 0.99 for supine and prone, respectively).
      When supine, lung area was 15.4 +/- 3.1 cm2, and FRC was 19.5 +/- 7.3 ml. In
      prone position, lung area was 16.7 +/- 4.2 cm2, and FRC 23.0 +/- 9.4 ml. There
      was a moderate to strong positive correlation between lung area and FRC for both
      positions (supine: r = 0.57, P < 0.03; prone: r = 0.63, P < 0.02). Lung area
      measured by computed radiography is a reproducible and practical method for
      estimating lung volume from routine chest X-rays in both supine and prone
      positions in mechanically ventilated preterm infants.

PMID- 15957185
TI  - Assessment of multiple displacement amplification for polymorphism discovery and
      haplotype determination at a highly polymorphic locus, MC1R.
AB  - The identification of common genetic variants such as single nucleotide
      polymorphisms (SNPs) in the human genome has become central in human population
      genetics and evolution studies, as well as in the study of the genetic basis of
      complex traits and diseases. Crucial for the accurate identification of genetic
      variants is the availability of high quality genomic DNA (gDNA). Since popular
      sources of gDNA (buccal cells, lymphocytes, hair bulb) often do not yield
      sufficient quantities of DNA for molecular genetic applications, whole genome
      amplification methods have recently been introduced to generate a renewable
      source of double-stranded linear DNA. Here, we assess the fidelity of one method,
      multiple displacement amplification (MDA), which utilizes bacteriophage Phi29 DNA
      polymerase to generate amplified DNA from an original source of gDNA, in a
      representative SNP discovery and genetic association study at the melanocortin 1
      receptor (MC1R) locus, a highly polymorphic gene in humans involved in skin and
      hair pigmentation. We observed that MDA has high fidelity for novel SNP discovery
      and can be a valuable tool in generating a potentially indefinite source of DNA.
      However, we observed an allele amplification bias that causes genotype miscalls
      at heterozygous sites. At loci with multiple polymorphic sites in linkage
      disequilibrium, such as at MC1R, this bias can create a significant number of
      heterozygote genotype errors that subsequently misrepresents haplotypes.

PMID- 15957186
TI  - Neurotensin and the neurotensin receptor-3 in microglial cells.
AB  - Microglia motility plays a crucial role in response to lesion or exocytotoxic
      damage of the cerebral tissue. The neuropeptide neurotensin elicited the
      migration of the human microglial cell line C13NJ by a mechanism dependent on
      both phosphatidylinositol-3 kinase (PI3 kinase) and mitogen-activated protein
      (MAP) kinases pathways. The effect of neurotensin on cell migration was blocked
      by the neurotensin receptor-3 propeptide, a selective ligand of this receptor.
      The type I neurotensin receptor-3 was the only known neurotensin receptor
      expressed in these microglial cells, and its activation led to the
      phosphorylation of both extracellular signaling-regulated kinases Erk1/2 and Akt.
      Furthermore, the effect of neurotensin on cell migration was preceded by a
      profound modification of the F-actin cytoskeleton, particularly by the rapid
      formation of numerous cell filopodia. Both the motility and the filopodia
      appearance induced by neurotensin were totally blocked by selective inhibitors of
      MAP kinases or PI3 kinase pathways. In the murine microglial cell line N11, the
      neurotensin receptor-3 is also the only neurotensin receptor expressed, and its
      activation by neurotensin leads to the phosphorylation of both Erk1/2 and Akt. In
      these cells, neurotensin induces the gene expression of several
      cytokines/chemokines, including MIP-2, MCP-1, interleukin-1beta and tumor
      necrosis factor-alpha. This induction is dependent on both protein kinases
      pathways. We observed that the effect of neurotensin on the cytokine/chemokine
      expression is also inhibited by the neurotensin receptor-3 propeptide. This is
      the demonstration that the neurotensin receptor-3 is functional and mediates both
      the migratory action of neurotensin and its induction of chemokines/cytokines
      expression.

PMID- 15957187
TI  - Immortalized human microglial cell line: phenotypic expression.
AB  - Microglia are a major neuroglial component of the CNS, playing an important role
      as resident immunocompetent and phagocytic cells in the CNS in the event of
      injury and disease. To understand the role of microglia in the CNS in health and
      diseases, we have recently established an immortalized clonal cell line of human
      microglia, HMO6, from human embryonic telencephalon tissue by using a retroviral
      vector encoding v-myc. This immortalized microglia HMO6 cell line exhibits cell
      type-specific antigens for microglia, including CD11b (Mac-1), CD68, CD86 (B7-2),
      HLA-ABC, HLA-DR, and RCA-1 lectin, and actively phagocytoses latex beads.

PMID- 15957189
TI  - CT-based description and phyletic evaluation of the archaic human calvarium from
      Ceprano, Italy.
AB  - The discovery in 1994, of a fossilized human calvarium near Ceprano, Italy, dated
      about 800-900 thousand years before present, opened a new page for the study of
      human evolution in Europe. It extended the continental fossil record over the
      boundary between Early and Middle Pleistocene for the first time and revealed the
      cranial morphology of humans that where probably ancestral to both Neanderthals
      and modern Homo sapiens. A tomographic analysis of the Italian specimen is
      reported here in order to describe size and shape, vascular traces, and other
      features of the endocranium, as well as some relevant ectocranial traits
      (particularly of the frontal region). Our results show that the Ceprano calvarium
      displays plesiomorphies shared by early Homo taxa, involving a general archaic
      phenotype. At the same time, the presence of some derived features suggests a
      phylogenetic relationship with the populations referred to the subsequent
      polymorphic species H. heidelbergensis. The morphology of the supraorbital
      structures is different from the double-arched browridge of the African H.
      ergaster, while its superior shape shows similarities with African Middle
      Pleistocene specimens (Bodo, Kabwe). In contrast, the relationship between
      supraorbital torus and frontal squama points to an archaic pattern of the
      relationship between face and vault, associated to moderately narrow frontal
      lobes and limited development of the upper parietal areas. Despite a nonderived
      endocranial shape, the increase of cranial capacity (related to a general
      endocranial widening) and the probable absence of a clear occipital projection
      also suggest an evolutionary independence from the Asian H. erectus lineage. This
      analysis therefore supports the conclusion that the Ceprano calvarium represents
      the best available candidate for the ancestral phenotype of the cranial variation
      observed among Middle Pleistocene fossil samples in Africa and Europe.
      Nevertheless, a proper taxonomic interpretation of this crucial specimen remains
      puzzling.

PMID- 15957190
TI  - Effect of sulforaphane on micronucleus induction in cultured human lymphocytes by
      four different mutagens.
AB  - Isothiocyanates (ITCs) are commonly found in cruciferous vegetables. A variety of
      biological activities have been ascribed to ITCs, such as inhibition of
      cytochrome P450 enzymes and induction of phase II enzymes in animal models. ITCs
      are also able to block cell-cycle progression and induce apoptosis in human
      cancer cells in vitro. In this study, we evaluated the ability of the ITC
      sulforaphane to protect cultured human lymphocytes from micronucleus (MN)
      induction by four different mutagens: ethyl methanesulfonate (EMS), vincristrine
      (VIN), H(2)O(2) and mitomycin C (MMC). To understand the mechanisms of action of
      sulforaphane, the cultures were treated with the compound before, during and
      after treatment with the mutagens; in addition, the cultures were evaluated for
      the induction of apoptosis. Up to 10 microM, sulforaphane was non-genotoxic by
      itself, while 30 microM sulforaphane reduced the replicative index of the cells
      by more than 60%. Moreover, 1-10 microM sulforaphane reduced the MN frequency
      induced by EMS, VIN, H(2)O(2) and MMC in at least one of the treatment protocols;
      it had no effect on H(2)O(2)-MN induction in the post-treatment protocol, and it
      increased MN induction by MMC in the pre-treatment protocol. Apoptosis was
      produced in the cultures treated with sulforaphane alone. The fraction of
      apoptotic cells was increased after co- or post-treatment with sulforaphane and
      EMS and MMC, suggesting that sulforaphane-mediated apoptosis may remove highly
      damaged cells induced by these agents. Other mechanisms are involved in the anti
      genotoxic activity of sulforaphane against VIN and H(2)O(2). Taken together, our
      findings indicate that under certain conditions sulforaphane possesses anti
      genotoxic activity in vitro and that further studies are warranted to
      characterize this property in vivo.

PMID- 15957191
TI  - Improved single-cell gel electrophoresis assay for detecting DNA damage in
      Eisenia foetida.
AB  - The earthworm (Eisenia foetida) is an attractive sentinel species for detecting
      genotoxicity in soil. In this study, an improved single-cell gel electrophoresis
      (SCGE) assay was developed for detecting DNA damage in the coelomocytes
      (lymphocytes) of earthworms. Coelomocytes were obtained from the coelomic fluid
      using a modified extrusion medium that did not include the mucolytic agent
      guaiacol. The extruded coelomocytes contained at least three types of cells:
      eleocytes (75% of the total), amoebocytes, and granulocytes. The DNA migration
      parameters were determined for untreated cells of each type in order that the
      assay could be performed with minimum inter- and intra-individual variation. In
      addition, lysis time was reduced to 10 min, and only one neutralization step was
      used. DNA damage was detected in isolated eleocytes treated with hydrogen
      peroxide and cadmium, and in eleocytes from earthworms exposed for up to 21 days
      to soil containing polycyclic aromatic hydrocarbons. The SCGE assay using
      earthworm eleocytes appears to be a sensitive biomarker for evaluating exposure
      to genotoxic compounds.

PMID- 15957193
TI  - Skull base approaches in the pediatric population.
AB  - BACKGROUND: This study aimed to examine the surgical, oncologic, and
      developmental results of infants and children undergoing extirpation of skull
      base tumors. METHODS: Sixty-seven children aged 0.5 to 18 years (mean, 11 years)
      who were operated on during a 6-year period made up the study cohort. Eighteen
      cases (27%) involved malignant tumors, and 49 (73%) involved benign tumors. The
      most common benign tumors were craniopharyngioma (n = 10) and juvenile
      nasopharyngeal angiofibroma (n = 8). The most common malignant tumor was sarcoma
      (n = 5). Thirty-six tumors (55%) involved the anterior skull base, and the rest
      involved the lateral (n = 24) and posterior (n = 7) skull base. Subcranial,
      transfacial, and subfrontal approaches were used for extirpation of anterior
      skull base tumors. Voluminous or malignant tumors were excised by use of combined
      approaches (subcranial-transfacial, subcranial-degloving, or pterional
      degloving). Twenty-two children underwent adjuvant therapy (chemotherapy,
      radiation, or both). Postoperative follow-up was 3 to 60 months. RESULTS: No
      severe postoperative complications (ie, meningitis, cerebrospinal fluid leak,
      tension pneumocephalus) and no perioperative mortality occurred. Two and a half
      years later, 54 of the children (80%) are alive and well. Five children, two with
      optic glioma and one each with squamous cell carcinoma, ependymoma, and
      germinoma, have died of their disease. The subcranial approach had no cosmetic
      impact on the craniofacial development of the patients. CONCLUSION: The
      extirpation of skull base tumors by use of conventional surgical techniques is
      feasible and safe among infants and children. The complication and mortality
      rates are lower than those in adults. The long-term cosmetic effect of the
      subcranial approach is negligible.

PMID- 15957192
TI  - Genotoxicity of acrylamide and its metabolite glycidamide administered in
      drinking water to male and female Big Blue mice.
AB  - The recent discovery of acrylamide (AA), a probable human carcinogen, in a
      variety of fried and baked starchy foods has drawn attention to its genotoxicity
      and carcinogenicity. Evidence suggests that glycidamide (GA), the epoxide
      metabolite of AA, is responsible for the genotoxic effects of AA. To investigate
      the in vivo genotoxicity of AA, groups of male and female Big Blue (BB) mice were
      administered 0, 100, or 500 mg/l of AA or equimolar doses of GA, in drinking
      water, for 3-4 weeks. Micronucleated reticulocytes (MN-RETs) were assessed in
      peripheral blood within 24 hr of the last treatment, and lymphocyte Hprt and
      liver cII mutagenesis assays were conducted 21 days following the last treatment.
      Further, the types of cII mutations induced by AA and GA in the liver were
      determined by sequence analysis. The frequency of MN-RETs was increased 1.7-3.3
      fold in males treated with the high doses of AA and GA (P < or = 0.05; control
      frequency = 0.28%). Both doses of AA and GA produced increased lymphocyte Hprt
      mutant frequencies (MFs), with the high doses producing responses 16-25-fold
      higher than that of the respective control (P < or = 0.01; control MFs = 1.5 +/-
      0.3 x 10(-6) and 2.2 +/- 0.5 x 10(-6) in females and males, respectively). Also,
      the high doses of AA and GA produced significant 2-2.5-fold increases in liver
      cII MFs (P < or = 0.05; control MFs = 26.5 +/- 3.1 x 10(-6) and 28.4 +/- 4.5 x
      10(-6)). Molecular analysis of the mutants indicated that AA and GA produced
      similar mutation spectra and that these spectra were significantly different from
      that of control mutants (P < or = 0.001). The predominant types of mutations in
      the liver cII gene from AA- and GA-treated mice were G:C-->T:A transversions and 
      1/+1 frameshifts in a homopolymeric run of Gs. The results indicate that both AA
      and GA are genotoxic in mice. The MFs and types of mutations induced by AA and GA
      in the liver are consistent with AA exerting its genotoxicity in BB mice via
      metabolism to GA.

PMID- 15957195
TI  - California stem-cell institute fights legal challenges.

PMID- 15957194
TI  - Clinical value of genetically diagnosed lymph node micrometastasis for patients
      with oral squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence and
      clinical significance of genetically diagnosed lymph node micrometastasis for
      patients with oral squamous cell carcinoma (SCC). METHODS: A total of 495 lymph
      nodes obtained from 21 patients with primary oral SCCs that had p53 mutations
      were examined for corresponding p53 mutations in lymph nodes using mutant allele
      specific amplification (MASA). RESULTS: Among 476 histologically negative nodes,
      44 were scored as positive for metastasis by MASA. All 19 histologically positive
      lymph nodes were genetically positive. Four of the 10 pN0 cases and nine of the
      11 pN-positive cases had genetically positive micrometastases. Four patients who
      had five or more genetically positive lymph nodes located in three or more
      levels, three with disease staged as pN0 or pN1, died of cancer. CONCLUSIONS:
      These results indicate that a high rate of micrometastasis in cervical lymph
      nodes of oral SCCs and patients with multiple or lower neck spread of
      micrometastases have a poor prognosis; they should be treated with postoperative
      adjuvant therapy.

PMID- 15957196
TI  - A six-factor model of cognition in schizophrenia and related psychotic disorders:
      relationships with clinical symptoms and functional capacity.
AB  - Confirmatory factor analysis was used to examine a proposed factor structure of a
      comprehensive neuropsychological battery used to study patients with
      schizophrenia and related psychotic disorders (n = 209). An a priori six-factor
      model and five nested models were evaluated successively, using maximum
      likelihood confirmatory factor analysis. In all multifactor models, the factors
      were significantly intercorrelated. A six-factor model with two pairs of
      correlated errors fit the neuropsychological data significantly better than
      competing models with fewer factors. The six factors included verbal
      crystallized, attention/working memory, verbal episodic memory, speed of
      information processing, visual episodic memory, and reasoning/problem solving.
      Severity of negative symptoms was significantly associated with worse performance
      on attention/working memory and verbal crystallized factors, but positive
      symptoms, depression, and a summary measure of psychopathology were not
      significantly related to neuropsychological performance. Impairment on a
      performance-based measure of functional capacity was significantly related to all
      neuropsychological factors. A simultaneous confirmatory factor analysis using the
      original sample and a group of healthy subjects (n = 131) demonstrated that the
      six-factor model of cognition was generalizable and applied equally well to both
      groups.

PMID- 15957197
TI  - At issue: Sex and gender in schizophrenia.
AB  - Using data collected in a study of sex differences in schizophrenia, I undertook
      this study to show the utility of distinguishing between sex and gender in the
      study of schizophrenia. Schizophrenia and schizoaffective disorder were combined
      to yield 213 patients (141 men, 72 women). There were 98 healthy controls (41
      men, 57 women). The relative contributions of sex and gender to the prediction of
      age of first hospitalization and neuropsychological functioning were examined in
      linear regression analyses. Sex, but not gender, was a significant predictor of
      age at first hospitalization, even when controlling for illness severity. Among
      patients, sex and gender significantly contributed to the prediction of
      neuropsychological performance, beyond the contributions of education, age, and
      illness severity. Comparable results were found among healthy controls, although
      gender was significant only for women. For both healthy subjects and patients,
      more frequent endorsement of female typical social roles predicted better
      neuropsychological functioning. Being female also predicted higher
      neuropsychological scores in patients. The findings suggest that some aspects of
      schizophrenia study, such as the disorder's onset, may be best pursued from a
      more biological (sex difference) perspective, while a sociocultural (gender
      difference) perspective may best serve other aspects of study, such as
      neuropsychological functioning.

PMID- 15957198
TI  - Are negative symptoms associated with functioning deficits in both schizophrenia
      and nonschizophrenia patients? A 10-year longitudinal analysis.
AB  - The current analyses assess the functional correlates of negative symptoms across
      diagnoses and across time to assess the appropriateness of a dimensional approach
      to the study of negative symptoms--specifically, whether negative symptoms should
      be studied as a single construct across diagnostic groups. Seventy-two
      schizophrenia/schizoaffective, 36 other psychotic, and 42 nonpsychotic depressed
      patients were recruited at index hospitalization and were followed up 4.5, 7.5,
      and 10 years later. At each followup assessment, data were collected on symptoms
      and adaptive and cognitive functioning. Analyses indicated that negative symptoms
      showed some similar functional associates in all three diagnostic groups,
      although results were strongest for the schizophrenia spectrum patients. Negative
      symptoms at the 10-year followup were associated with different patterns of
      social deficits prior to index hospitalization in the three diagnostic groups.
      The data provide some support for a dimensional approach to the study of mental
      illness, with negative symptoms associated with deficits across diagnosis, but
      also provide evidence of some diagnostic differences.

PMID- 15957199
TI  - Early treatment-induced improvement of negative symptoms predicts cognitive
      functioning in treatment-naive first episode schizophrenia: a 2-year followup.
AB  - Studying neuroleptic-naive first episode schizophrenia is a strategy for
      investigating clinical and neuropsychological abnormalities at a very early phase
      of the disease without confounding influences of illness duration and medication
      effects. We examined the clinical and neuropsychological time course over 2 years
      in 32 neuroleptic-naive first episode patients (20 males, 12 females) and 21
      healthy individuals with similar sociodemographic characteristics. Early
      treatment-induced reduction of negative symptoms predicted superior cognitive
      performance throughout followup in the domains of verbal fluency, attention, and
      non-verbal learning and memory. There were no associations between psychotic or
      disorganized symptoms and cognitive variables. These findings suggest an
      important relationship between treatment efficacy of antipsychotic medication and
      the longer term course of cognitive deficits in schizophrenia.

PMID- 15957200
TI  - Reduced red blood cell membrane essential polyunsaturated fatty acids in first
      episode schizophrenia at neuroleptic-naive baseline.
AB  - There is emerging evidence in schizophrenia of membrane abnormalities, primarily
      reductions in the essential omega-3 and omega-6 series of polyunsaturated fatty
      acids (PUFA). Because previous studies have largely been in chronic patients, it
      is not known whether these membrane abnormalities also occur early in illness. In
      the present study, red blood cell membrane fatty acid levels were determined by
      capillary gas chromatography from 24 neuroleptic-naive patients with first
      episode schizophrenia or schizoaffective disorder and 31 age-matched normal
      controls. Relative to normal subjects, patients had significant reductions in
      total PUFA (-13%) but not in monounsaturated or saturated fatty acids.
      Specifically, significant reductions were found in arachidonic acid (-18%),
      docosapentaenoic acid (-36%), and docosahexaenoic acid (-26%) concentrations.
      These reductions were not related to age, gender, smoking status, or cotinine
      levels. These results confirm previous findings of membrane deficits in
      schizophrenia and show that significant PUFA reductions occur early in the
      illness, prior to initiation of treatment, raising the possibility that these
      deficits are trait related. The findings also suggest that membrane fatty acid
      losses are quite specific to the highly unsaturated fatty acids.

PMID- 15957201
TI  - A randomized controlled trial of integrated versus parallel housing services for
      homeless adults with severe mental illness.
AB  - This study compared two contemporary approaches to linking housing and mental
      health services. In the integrated housing program, case management and housing
      services were provided by teams within a single agency and were closely
      coordinated. In the parallel housing condition, case management services were
      provided by mobile assertive community treatment teams and housing by routine
      community-based landlords. Adults with severe mental illness who were at high
      risk for homelessness (n = 121; 72.7% schizophrenia spectrum) were assigned
      randomly to integrated or parallel housing services and followed for 18 months.
      Integrated housing services led to more days of stable housing and greater life
      satisfaction than parallel housing services, especially for male participants.
      Integrated housing services were also associated with greater reductions in
      psychiatric symptoms. Closer integration between clinical and housing services,
      and greater use of supervised living settings, led to more time in stable housing
      for participants in the integrated housing services condition and was associated
      with greater gains in several outcome domains.

PMID- 15957202
TI  - Examining the factor structure of the recovery assessment scale.
AB  - This article follows up on earlier research examining the factor structure of a
      measure of recovery from serious mental illness. Exactly 1,824 persons with
      serious mental illness who were participating in the baseline interview for a
      multistate study on consumer-operated services completed the Recovery Assessment
      Scale (RAS) plus measures representing hope, meaning of life, quality of life,
      symptoms, and empowerment. Results of exploratory and subsequent confirmatory
      factor analyses of the RAS for random halves of the sample yielded five factors:
      personal confidence and hope, willingness to ask for help, goal and success
      orientation, reliance on others, and no domination by symptoms. Subsequent
      regression analyses showed that these five factors were uniquely related to the
      additional constructs assessed in the study. We compared these findings with
      those of other studies to summarize the factor structure that currently emerges
      on recovery.

PMID- 15957203
TI  - Bibliography. Current world literature. Pulmonology.

PMID- 15957204
TI  - Bibliography. Current world literature. Surgery.

PMID- 15957205
TI  - A hybrid coating of biomimetic apatite and osteocalcin.
AB  - A novel hybrid coating of biomimetic apatite(BAp) and osteocalcin (OC) was
      prepared by incubating BAp-coated Ti6A14V coupons in an osteocalcin-containing
      medium. A significant amount (up to 1.0 wt %) of OC was adsorbed by the BAp
      coating within 3 h of incubation as demonstrated by high-performance liquid
      chromatography. Characterizations of the hybrid coating with environmental
      scanning microscopy and X-ray diffraction indicated that protein adsorption does
      not alter the microstructure of the coating. The presence of OC in the hybrid
      coating was visualized with fluorescence microscopy using an immuno-labeling
      procedure. The affinity of OC to the BAp coating was examined using a 20-h
      elution test in phosphate-buffered saline and only a minimal amount (<10%) of the
      loaded OC was eluted out. When the coating was fully dissolved in hydrochloric
      acid solution after elution, about 78% of the loaded OC could be recovered.
      Enzyme-linked immunosorbent assay and peptide sodium dodecylsulfate
      polyacrylamide gel electrophoresis confirmed the integrity and activity of OC
      molecules throughout the tests. The preliminary cell culture tests showed a
      significant effect of OC on the attachment and proliferation of osteoblasts. The
      quick loading profile and high affinity of OC to the BAp coating make it an ideal
      candidate for the hybrid coating preparation in clinical environment.

PMID- 15957206
TI  - The question of forbidden knowledge.

PMID- 15957207
TI  - The question of forbidden knowledge.

PMID- 15957209
TI  - Abstracts of the 41st Annual Meeting of the American Society of Clinical Oncology
      (ASCO). May 13-17, 2005. Orlando, Florida, USA.

PMID- 15957208
TI  - New Dynamics of HIV Risk Among Drug-Using Men Who Have Sex With Men. Proceedings
      of a workshop. March 1-2, 2004.

PMID- 15957210
TI  - Abstracts of the 41st Annual Meeting of the American Society of Clinical Oncology
      (ASCO). May 13-17, 2005. Orlando, Florida, USA. (Part 2).

PMID- 15957211
TI  - Abstracts of the 8th International Symposium on Myelodysplastic Syndromes. May 12
      15, 2005, Nagasaki, Japan.

PMID- 15957212
TI  - Abstracts of the 5th Annual Meeting of the Federation of Clinical Immunology
      Societies. Boston, Massachusetts, USA. May 12-16, 2005.

PMID- 15957213
TI  - Molecular analysis of the En/Spm transposable element system of Zea mays.
AB  - The nucleotide sequence of the autonomous transposable element En-1 isolated from
      the wx-844::En-1 allele has been determined. En-1 is 8287 bp long. The structure
      of the mosaic gene 1, coding for the major En transcript, has been established.
      The promoter gene 1 is located in the highly structured left end of the element
      and the gene spans almost the entire length of En-1. The first intron of gene 1
      is 4434 nucleotides long and contains two large open reading frames, 2714 bp and
      761 bp in size, which hybridize to minor RNA species in Northern blot
      experiments.

PMID- 15957214
TI  - Molecular cloning of the c locus of Zea mays: a locus regulating the anthocyanin
      pathway.
AB  - The c locus of Zea mays, involved in the regulation of anthocyanin biosynthesis,
      has been cloned by transposon tagging. A clone (# 18En) containing a full size
      En1 element was initially isolated from the En element-induced mutable allele c
      m668655. Sequences of clone # 18En flanking the En1 element were used to clone
      other c mutants, whose structure was predicted genetically. Clone #23En (isolated
      from c-m668613) contained a full size En1 element, clone #3Ds (isolated from c
      m2) a Ds element and clone # 5 (isolated from c+) had no element on the cloned
      fragment. From these data we conclude that the clones obtained contain at least
      part of the c locus. Preliminary data on transcript analysis using a 1-kb DNA
      fragment from wild-type clone # 5 showed that at least three transcripts are
      encoded by that part of the locus, indicating that c is a complex locus.

PMID- 15957215
TI  - Mitotic spindle pulls but fails to separate chromosomes in type II DNA
      topoisomerase mutants: uncoordinated mitosis.
AB  - The fission yeast top2 locus is defined by five temperature-sensitive mutations
      that cause heat-labile activity of type II DNA topoisomerase in the cell
      extracts. We show that the top2 locus is a structural gene for type II
      topoisomerase by cloning a genomic DNA fragment that complements top2. The top2
      mutants at restrictive temperature produce abnormal chromosomes at the time of
      mitosis; these are transiently extended into filamentous structures along with
      the elongating mitotic spindle but are not separated. A primary defect in top2
      appears to be the formation of aberrant mitotic chromosomes inseparable by the
      force generated by the spindle apparatus. Consistently, the top2 cells that
      become lethal during mitosis contain a catenated dimer of an ARS plasmid. DNA and
      RNA continue to be synthesized if cytokinesis is blocked. Uncoordinated mitosis,
      that is the occurrence of spindle dynamics without chromosome separation, is
      revealed in top2, and is discussed in relation to mitotic regulation. Different
      phenotypes between top2 and top1-top2 described in the present paper can be
      explained by a previously proposed hypothesis that type II topoisomerase has dual
      in vivo functions: one that decatenates and unknots duplex DNAs is essential in
      mitosis, whereas the other which relaxes supercoils is required throughout the
      cell cycle if type I topoisomerase is absent.

PMID- 15957217
TI  - Secretion in yeast: translocation and glycosylation of prepro-alpha-factor in
      vitro can occur via an ATP-dependent post-translational mechanism.
AB  - In an in vitro system comprising a yeast cell-free translation system, yeast
      microsomes and mRNA encoding prepro-alpha-factor, the translocation of this
      protein across the membrane of the microsomal vesicle and its glycosylation could
      b uncoupled from its translation. Such post-translational processing is dependent
      upon the presence of ATP in the system. It is not, however, affected by a variety
      of uncouplers, ionophores or inhibitors, including carbonyl cyanide m
      chlorophenyl hydrazone (CCCP), valinomycin, nigericin, dinitrophenol (DNP),
      potassium cyanide (KCN) or N-ethyl maleimide (NEM). This mechanism of
      translocation is significant as it indicates that a protein of 18 000 daltons is
      capable of crossing an endoplasmic reticulum-derived membrane post
      translationally. For the moment, this phenomenon seems to be restricted to prepro
      alpha-factor in the yeast in vitro system. Neither invertase nor IgG chi light
      chain could be translocated post-translationally in yeast, nor was such
      processing observed for prepro-alpha-factor in a wheat germ system supplemented
      with canine pancreatic microsomes.

PMID- 15957216
TI  - Chromosome walking shows a highly homologous repetitive sequence present in all
      the centromere regions of fission yeast.
AB  - By cloning centromere-linked genes followed by partial overlapping hybridization,
      we constructed a 210-kb map encompassing the centromere in chromosome II and a 60
      kp map near the centromere of chromosome I in the fission yeast
      Schizosaccharomyces pombe which has three chromosomes. Integration of the cloned
      sequences into the chromosome and subsequent analyses of tetrads and dyads
      revealed an approximately 50 kb long domain located in the middle of the 210-kb
      map, tightly linked to the centromere and greatly reduced in meiotic
      recombination. This domain contained at least two classes of repetitive
      sequences. One, designated yn1, was specifically present in a particular
      chromosome and repeated three times in the 210-kb map of chromosome II. The
      other, designated dg, was located in all the centromere regions of three
      chromosomes. One (dgI) and two (dgIIa, dgIIb) copies of the dg were found in the
      maps of chromosomes I and II, respectively. The dgIIa and dgIIb were arranged
      with a 20-kb interval within the repetitive domain. In the centric region of
      chromosome II, 3-4 copies of the dg appeared to exist. By determining the
      nucleotide sequences of dgI and dgIIa, the dg was identified to be 3.8 kb long.
      The sequence homology was 99% between dgI and dgIIa. These extraordinarily
      homologous sequences seemed not to be transcribed into RNA nor to be encoding any
      protein. The larger part of the dg sequence was internally non-repetitious, a 600
      bp region existed which consisted of stretches of several short repeating units.
      The structures in or surrounding the centromeres of S. pombe appear to be much
      more complex than those of the budding yeast Saccharomyces cerevisiae.

PMID- 15957218
TI  - Archaebacteria: transcription and processing of ribosomal RNA sequences in
      Halobacterium cutirubrum.
AB  - The chromosome of Halobacterium cutirubrum contains a single ribosomal RNA gene
      cluster. The 5' to 3' organization of genes within this 6-kpb region is: 16S,
      alanine tRNA, 23S, 5S, cysteine tRNA. The entire gene cluster is transcribed as a
      single long primary transcript; processing of mature RNA sequences from the 5'
      region of the transcript begins prior to the completion of synthesis at the 3'
      end. There are five conserved octanucleotide direct repeats (TGCGAACG) in the 900
      bp 5'-flanking sequence in front of the 16S gene. The positions of these repeat
      sequences correspond to the different 5' ends of the primary transcript and
      probably represent the RNA polymerase start sites. The 16S and 23S rRNA genes are
      surrounded by long nearly perfect inverted repeat sequences. These sequences
      probably form duplex structures in the primary transcript and are recognized by
      an RNaseIII-like endonuclease activity that carries out the initial excision of
      the precursor 16S and 23S rRNA sequences. These precursors are rapidly trimmed
      tot he mature 16S and 23S molecules and assembled into ribosomal particles. The
      processing sites for 5S rRNA appear to be at or very near to the mature ends of
      the 5S molecule. The tRNA sequences are processed with reduced efficiency from
      the primary transcript. Nuclease cuts have been detected at the ends as well as
      in the middle of the cysteine tRNA sequence suggesting that there may be
      alternative processing pathways, one resulting in proper excision of the mature
      tRNA sequence and the other resulting in improper excision and degradation of the
      tRNA sequence. The transcription termination sequence is believed to be at or
      beyond an AT-rich sequence preceded by a GC-rich sequence located distal to the
      cysteine tRNA gene.

PMID- 15957219
TI  - [A soluble TNF-alpha receptor agent: etanercept].

PMID- 15957220
TI  - Administration and management training for laboratory animal residents.

PMID- 15957221
TI  - Balancing animal well-being, cost, and employee health and safety in caging
      design and selection.

PMID- 15957222
TI  - Implementing housing refinements in rhesus macaque colony.

PMID- 15957224
TI  - Abstracts of the 89th Meeting of the German Society of Pathology. 18-21 May 2005,
      Wuppertal, Germany.

PMID- 15957223
TI  - An NIRS matrix for detecting and correcting cerebral oxygen desaturation events
      during surgery and neuroendovascular procedures.
AB  - BACKGROUND: Transcranial cerebral oximetry was developed for early detection of
      cerebral hypoxia and to avoid cerebral dysfunctions. However, near infrared
      spectroscopy (NIRS) data obtained during surgery are subject to intrinsic and
      extrinsic influences that have to be accounted for when interpreting the
      recordings. METHODS: We developed an NIRS matrix to provide brief information for
      specific intervention to correct changes of cerebral oxygen saturation (COS).
      Selected vital data and the descriptors of cerebrovascular and neurofunctional
      status were linked to logistic chains. RESULTS: The matrix is horizontally and
      vertically grouped and contains five descriptors: 1. change of COS; 2. key
      variable (parameter related to the change of COS); 3. associated parameters
      (vital data that do not cause COS alterations); 4. interpretation of values or
      preconditions most probably due to COS changes; and 5. the intervention most
      likely to normalize the COS or return it to baseline. The descriptors are grouped
      horizontally to a logistics chain. CONCLUSION: The modular expandable NIRS matrix
      we describe has promise for clinical use in surgical, neurointerventional, and
      anaesthesiological contexts.

PMID- 15957225
TI  - Proceedings of the XXXII Congress of the Spanish Society of Physiological
      Sciences. 10-13 February 2005, Sevilla, Spain.

PMID- 15957226
TI  - The Functionally Univentricular Circulation: from analysis of fluid dynamics to
      surgical procedures. Proceedings of an international workshop. 25-26 October
      2002, Massa, Italy.

PMID- 15957227
TI  - Magnetic tweezers tease out dissociation.

PMID- 15957228
TI  - Detecting doping.

PMID- 15957229
TI  - Where the lipids are.

PMID- 15957230
TI  - A random walk through electron-transfer kinetics.

PMID- 15957231
TI  - Beyond the t-test: statistical equivalence testing.

PMID- 15957232
TI  - An outbreak of Escherichia coli O157:H7 associated with a children's water spray
      park and identified by two rounds of pulsed-field gel electrophoresis testing.

PMID- 15957233
TI  - A notable phenomenon recapitulated. A fusion product of a murine lymphoma cell
      and a leukemia virus-neutralizing antibody-producer host plasma cell formed
      spontaneously and secreting the specific antibody continuously.
AB  - In the mid-1960s the #620 cell passage line of a murine lymphoma-leukemia was
      developed at the Section of Clinical Tumor Virology and Immunology, Department of
      Medicine, The University of Texas M.D. Anderson Hospital in Houston, TX. The
      diploid lymphoma cells released a retrovirus and were antigenic in young adult
      Swiss (YAS) mice. Small lymphoma cell inocula were rejected with immunity
      acquired against large inocula of lymphoma cells. Tissue sections revealed the
      "starry sky" configurations. In one of the tissue cultures set up from lymphoma
      #620, a cell line consisting of large round poly- or tetraploid cells arose and
      was referred to as lymphoma cell line #818. The #818 cells grew in suspension
      cultures and in the form of large, lethal ascitic tumors in YAS mice. Diploid
      #620 lymphoma cells stained for retroviral antigens; #818 cells stained both for
      retroviral antigens and immunoglobulins. Fluids withdrawn from #818 cultures
      neutralized the leukemia virus in spleen focus assays. Immunoglobulin
      precipitated from #818 suspension culture fluids strongly and specifically
      neutralized the leukemia virus. The growth of #620 or #818 cells in YAS mice
      treated with rabbit anti-lymphoma cell immune sera was strongly inhibited but
      culture fluids of #818 cells showed weak and insignificant inhibition against
      leukemia-lymphoma #620 (in one experiment, unpublished). In two experiments #620
      lymphoma cells were co-inoculated with immune spleen cells into the peritoneal
      cavities of YAS mice. The immune spleen cells derived from mice that rejected
      #620 cell inocula or were actively immunized with a photodynamically inactivated
      mouse leukemia virus vaccine. In the peritoneal cavities of mice co-inoculated
      with #620 cells and immune spleen cells, clones of large round cells emerged with
      tetra- or polyploid chromosomal modes. These cells stained for leukemia viral
      antigens and immunoglobulins. When passaged in YAS mice these cells induced
      lethal ascites tumors. It was concluded as early as in 1968-69 that an immune
      plasma cell can fuse with a lymphoma cell, if the lymphoma cell expresses
      retroviral antigens against which the plasma cell is producing a specific
      antibody. Some human lymphoma-leukemia cells express retroviral antigens and/or
      budding retroviral particles, whether due to the acquisition of new env sequences
      by incomplete resident endogenous retroviral genomes or due to the entry of
      exogenous retroviruses into lymphopoietic stem cells. In the Discussion
      illustrations are provided for the human cell line #778 established from a
      patient with "lymphosarcoma cell leukemia" in 1966. The malignant cells released
      unidentified retrovirus-like particles and fused with one another and with
      reactive lymphoid cells of the host. It should be investigated further if human
      lymphoma-leukemia cells could fuse with an immune plasma cell of the host and
      thus alter the clinical course of the disease.

PMID- 15957234
TI  - Murine herpesvirus pathogenesis: a model for the analysis of molecular mechanisms
      of human gamma herpesvirus infections.
AB  - Murine herpes virus (MHV), a natural pathogen originally isolated from free
      living rodents, constitutes the most amenable animal model for human gamma
      herpesviruses. Based on DNA sequence homology, this virus was classified as Murid
      Herpesvirus 4 to subfamily Gammaherpesvirinae. Pilot studies in our laboratory,
      using mice inoculated by the intranasal route, showed that MHV infects
      macrophages, B lymphocytes, lung alveolar as well as endothelial cells. From the
      lungs the virus spreads via the bloodstream to spleen and bone marrow and via the
      lymphatics to the mediastinal lymph nodes. Similarly to other gamma
      herpesviruses, MHV established life-long latency maintained in host B lymphocytes
      and macrophages. An IM-like syndrome (per analogy to EBV) may develop during
      acute MHV infection, in which the atypical T/CD8+ lymphocytes eliminate viral DNA
      carrying B cells expressing the M2 latency associated protein. During latency,
      the MHV LANA (a KSHV LANA homologue) maintains the latent viral genome, assuring
      its copying and partition to new carrier cells in the course of division of the
      maternal cell. The nonproductive latency is turned onto virus replication by
      means of Rta protein. The chronic lymphoproliferative syndrome of unclear
      pathogenesis, which occurs in a certain part of latent MHV carriers, is related
      to the expression of gamma herpesvirus common latency-associated genes such as v
      cyclin and/or to that of a virus-specific (M11/bcl-2) gene. This review attempts
      to summarize our knowledge concerning the function of MHV genes (either gamma
      herpesvirus common or MHV specific) related to immune evasion, latency and
      lymphoproliferation when highlighting the unsolved problems and/or controversial
      opinions.

PMID- 15957235
TI  - "Who has first observed planctomyces" (or data to the history of Planctomyces
      bekefii).
AB  - The first description of Planctomyces bekefii was published in eighty years ago
      by N. Gimesi in Hungary. The history and importance of this species is revealed
      in this article.

PMID- 15957236
TI  - Incidence of oropharyngeal candidosis in stem cell transplant (SCT) patients.
AB  - Eighty persons with haematological malignancies receiving stem cell
      transplantation (SCT) were examined over a 24 months period. Hyposalivation, a
      common complaint in patients treated by intensive chemotherapy and radiotherapy
      can predispose to oral candidal colonisation as well. This study was focused on
      correlation between the fungal colonisation of the oral cavity and the total
      unstimulated saliva flow rate of 80 patients with haematological malignancies
      before and after stem cell transplantation and in addition, on their oral health
      state. Despite the fact that prior to being involved in the transplantation
      programme, the patients were subjected to dental examination and decayed teeth
      were found in 20 out of 80 patients (25%). From the 2233 different oropharyngeal
      specimens fungi were isolated before conditioning from 16 patients (20%), and
      during aplasia from 19 patients (23.7%). Objective xerostomia (unstimulated total
      saliva flow rate < or = 0.1 ml/min) was detected in 28 patients (35%). Stem cell
      transplant patients with pretransplant mouth dryness had higher incidence of
      Candida albicans and other fungal colonisation than those with normal saliva
      secretion.

PMID- 15957237
TI  - Being on the track of thimerosal. Review.
AB  - The common preservative thimerosal is one of the most important organic mercury
      compounds human populations are exposed to. It has toxic effect on several cell
      lines, and it also induces programmed cell death in in vitro experiments.
      Association is suggested between application of thimerosal-containing vaccines
      and the occurrence of neurodevelopmental disorders, like autism. While specific
      recommendations were made to eliminate thimerosal from vaccines, consistent
      evidence is still lacking for an association of exposure and disease.
      Unfortunately, it is very hard to study the molecular background of complex human
      diseases directly; however, investigations on more simple model organisms may
      lead to a better understanding of thimerosal as a possible disease inducing
      factor.

PMID- 15957238
TI  - Effect of herbizid and touchdown herbicides on soil fungi and on production of
      some extracellular enzymes.
AB  - Glucophilic and cellulose-decomposing fungi were significantly reduced in soil
      samples treated with 0.019-0.152 mg a.i./kg soil of the herbicides Herbizid and
      Touchdown. The decrease was regularly correlated with the doses of the two
      herbicides and persisted till the end of the experiment (12 weeks). The isolated
      fungi were found to be able to produce hydrolytic extracellular enzymes in solid
      media but with variable capabilities. The ability to produce enzymes was
      adversily affected by the incorporation of herbicides in culture media. Lower
      doses of herbicides were occasionally promotive to enzyme production and mycelial
      growth of some fungi. Incorporation of 50 ppm of Herbizid and Touchdown
      significantly activated amylase production and mycelial dry weight in cultures of
      Fusarium oxysporum, Mucor hiemalis and Penicillium chrysogenum. There was a
      significant increase in C1-cellulase produced by F. oxysporum and P.
      aurantiogriseum when cultures were treated with 50, 100 and 200 ppm of Herbizid
      which induced also more Cx-cellulase production by P. chrysogenum. Lipase and
      protease production was always lower in treated than in control fungal cultures.

PMID- 15957240
TI  - Winning strategies for a successful externship program.

PMID- 15957241
TI  - Respect in the relationship between nurses and clients.

PMID- 15957242
TI  - Experimental allergic encephalomyelitis in male Lewis rats subjected to calorie
      restriction.
AB  - This work analyzes the effect of calorie restriction on the development of
      experimental allergic encephalomyelitis (EAE) in Lewis rats. Plasma levels of
      ACTH, corticosterone, prolactin and growth hormone (GH) and mitogenic responses
      in submaxillary lymph nodes were measured. Male Lewis rats (6 weeks-old) were
      submitted to a calorie restriction equivalent to 66% of food restriction or to a
      normal diet. Fifteen days later, rats were injected with complete Freund's
      adjuvant plus spinal chord homogenate (SCH) or with complete Freund's adjuvant
      alone. Rats were monitored daily for clinical signs of EAE and were killed on day
      15 after immunization. Only rats subjected to normal diet exhibited clinical
      signs of the disease. The increase in plasma ACTH and corticosterone found after
      SCH immunization in controls was not detectable in calorie restricted rats.
      Likewise, the correlation between circulating ACTH and corticosterone was no
      longer found after calorie restriction. Generally, calorie restriction by itself
      augmented plasma ACTH or corticosterone and this increase was not further
      amplified by SCH immunization. Only calorie restricted rats exhibited augmented
      plasma prolactin levels after SCH immunization, and decreased plasma GH levels
      regardless of immunization. Calorie restriction depressed the mitogenic response
      of lymphoid cells to concanavalin A but not to lipopolysaccharide. Calorie
      restricted rats did not exhibit augmented mitogenic response to concanavalin A
      following SCH immunization as those found in controls. The results are compatible
      with the view that the course of EAE can be significantly modified by caloric
      restriction.

PMID- 15957243
TI  - Serum IL-10 and IL-6 levels at diagnosis as independent predictors of outcome in
      non-Hodgkin's lymphoma.
AB  - Interleukin 10 (IL-10) and interleukin 6 (IL-6) are widely investigated in solid
      tumors as being important prognostic factors. IL-10 and IL-6 serum levels were
      measured by enzyme-linked immunosorbent assay from sera taken from 40 non
      Hodgkin's lymphoma (NHL) patients before and after treatment and from 20 healthy
      controls. The patients had been observed for at least 18 months or until death.
      IL-10 and IL-6 were significantly higher in NHL patients compared to controls. IL
      6 was correlated with IL-10 (r = 0.451) and with B symptoms (weight loss > 10%
      during the last 6 months, unexplained fever and night sweats) (r = 0.447). IL-10
      and IL-6 were significantly higher in non survival compared to survival group.
      High pretreatment IL-10 and IL-6 was associated with poor overall survival. These
      results show that IL-10 and IL-6 levels are elevated in NHL patients and seem to
      suggest that simultaneous elevation of IL-10 and IL-6 is a powerful negative
      prognostic parameter in NHL.

PMID- 15957244
TI  - Effect of red wine on oxidative stress and hypercholesterolemia induced by
      feeding a high-cholesterol diet in rat.
AB  - The effect of red wine on oxidative stress and hypercholesterolemia induced by
      feeding a high-cholesterol diet (supplemented with 1.65% of cholesterol (w/w) for
      4 weeks) to female Wistar rats was examined. When red wine was simultaneously
      supplemented to high-cholesterol diet, total cholesterol, triglycerides,
      atherogenic index and lipid peroxidation products significantly decreased
      compared with the high-cholesterol diet alone, while GSH content and
      antioxidative enzymes activities were enhanced. In the hypercholesterolemic rat
      the excretion of fecal bile acids, as well as their plasma and hepatic
      concentrations were increased significantly. Administration of red wine enhanced
      these values, indicating an increase in the cholesterol degradation. These
      results suggest that red wine may have a protective effect against oxidative
      stress, hypercholesterolemia and atherogenic index induced by high-cholesterol
      diet.

PMID- 15957245
TI  - Creatine supplementation and performance in 6 consecutive 60 meter sprints.
AB  - Creatine is an ergogenic aid used in individual and team sports. The aim of this
      study is to analyze the effect of monohydrate creatine supplementation on
      physical performance during 6 consecutive maximal speed 60 meter races, and the
      changes induced in some characteristic biochemical and ventilatory parameters.
      The study was carried out on nineteen healthy and physically active male
      volunteers, and randomly distributed into two groups: Group C received a
      supplement of creatine monohydrate (20 g/day for 5 days) and group P received
      placebo. Tests were performed before and after supplementation. No significant
      changes were observed in weight or body water measured by bioimpedance or the sum
      of 7 skinfold or performance during the 60 meter races. Group C showed a
      statistically significant increase in plasma creatinine from 69.8 +/- 12.4 to
      89.3 +/- 12.4 micromol x L(-1) (p<0.05). In group C in the second control day
      (after creatine supplementation), expiratory volume V(E), O2 uptake and CO2
      production were lower after 2 minutes of active recovery period. These results
      indicate that creatine monohydrate supplementation does not appear to improve the
      performance in 6 consecutive 60 meter repeated races but may modify ventilatory
      dynamics during the recovery after maximal effort.

PMID- 15957246
TI  - Molecular identification of mutations in G6PD gene in patients with favism in
      Iran.
AB  - Glucose 6-phosphate dehydrogenase is a highly polymorphic enzyme encoded by a
      human X-linked gene (Xq2.8). This enzyme catalyses the first step of pentose
      phosphate pathway, that converts glucose 6-phosphate to 6-phosphogluconate with
      production of NADPH2. G6PD deficiency is the most common human metabolic inborn
      error affecting more than 400 million people world wide. The main clinical
      manifestations are acute hemolytic anemia and jaundice, triggered by infection or
      ingestion of Fava beans or oxidative drugs. A predominant variant of G6PD named
      Mediterranean is often associated with favism. This has been evident in several
      countries including Northern coastal provinces of Iran. Other current variants
      are Chatham and Cosenza. Molecular identification of the most prevalent mutations
      in G6PD gene was carried out in 71 males and females with G6PD deficiency. They
      were from Iranian Northern province of Golestan. DNA was extracted from blood
      samples and analyzed for known G6PD mutation by PCR and restriction fragment
      length polymorphisms (RFLP) technique. Adapting this method, revealed that
      Mediterranean mutation at nt 563(C-->T) is predominant in the area (69%) and
      26.7% of patients have Chatham mutation at nt 1003(G-->A). Findings indicate a
      higher prevalence of these mutations, in Golestan compared to Mazandaran (66.2%
      Mediterranean and 19% Chatham mutation) and Gilan (86.4% Mediterranean and 9.71%
      Chatham mutations). Cosenza mutation at nt 1376(G-->C), by PCR-RFLP technique was
      not found among other 3 samples (4.3%). The similarity of these results with
      mutations in Italy indicates probable existence of a common ancestral origin in
      the observed populations.

PMID- 15957247
TI  - Decreased splenic mRNA expression levels of TNF-alpha and IL-6 in diet-induced
      obese animals.
AB  - Obesity could be considered as a systemic low-grade inflammatory condition
      affecting inflammation markers. Adipose tissue synthesizes cytokines whose degree
      of elevation may depend on the obesity status. Recently, new information is
      collected on the cross-talking between immune system and adipose tissue in
      obesity. We report hereby that tumor necrosis factor alpha (TNF-alpha) and
      interleukin 6 (IL-6) gene expression in spleen of diet-induced obese animals were
      markedly decreased (more than 50%) as a consequence of the high fat feeding
      during five weeks. Interestingly, a very significant negative correlation was
      found between splenic TNF-alpha mRNA levels and total fat pads (r = -0.806, p =
      0.000). These findings support the hypothesis that TNF-alpha gene expression may
      follow different trends in obese animals adipocytes and splenocytes.

PMID- 15957250
TI  - Novel oxylipins formed from docosahexaenoic acid by potato lipoxygenase--10(S)
      hydroxydocosahexaenoic acid and 10,20-dihydroxydocosahexaenoic acid.
AB  - Potato tuber lipoxygenase (ptLOX) has been shown to catalyze the aerobic
      formation of at least four major oxygenated derivatives of DHA. Two of the
      products--7,17(S)- and 10,17(S)-dihydro(pero)xy-DHA [7,17- and 10,17-diH(P)DHA]-
      were formed from soybean 15-LOX-derived 17(S)-hydro(pero)xy-DHA [17(S)-H(P)DHA],
      whereas two novel oxylipin compounds--10(S)-hydro(pero)xy-DHA and 10,20
      dihydro(pero)xy-DHA [10(S)-H(P)DHA and 10,20-diH(P)DHA, respectively]--were the
      major direct products of DHA oxidation by ptLOX. The reactions proceeded
      relatively slowly but could be stimulated by catalytic amounts of SDS. Micromolar
      concentrations of 10(S)-HPDHA effectively abolished the kinetic lag period of
      ptLOX activation. Enzymatic activity with DHA or 17(S)-HPDHA as substrate was
      about 8% of that with linoleic acid--a standard natural ptLOX substrate--whereas
      17(S)-HDHA was converted at a rate of approximately 1%. The enzyme was relatively
      unstable and quickly inactivated during the reaction with DHA on with 17(S)-HPDHA
      (first-order kinetic constant of inactivation kin = 1.5 +/- 0.3 min(-1)), but not
      with 17(S)-HDHA. Both 7,17- and 10,20-diH(P)DHA were clearly products of double
      oxygenation catalyzed by soybean 15-LOX and/or ptLOX. Our observation that ptLOX
      could convert 17-HDHA to 10,17-diH(P)DHA indicates that this dihydroxylated
      derivative of DHA also can be formed via a double lipoxygenation mechanism.

PMID- 15957251
TI  - Effect of homocysteine, folates, and cobalamin on endothelial cell- and copper
      induced LDL oxidation.
AB  - Oxidation of LDL contributes to endothelial dysfunction and atherosclerosis. This
      process could be associated with hyperhomocysteinemia, a condition that can be
      reduced after folic acid treatment. Because a reduction in LDL oxidation may
      improve endothelial function, we studied the effect of some vitamins (folic acid,
      5-methyltetrahydrofolic acid, and vitamin B-12) on LDL oxidation, either in the
      presence or absence of homocysteine. For this purpose, two in vitro systems were
      used: an endothelial cell-catalyzed LDL oxidation system and a cell-free copper
      initiated LDL oxidation system. The kinetics of copper-catalyzed LDL oxidation
      was determined by continuous monitoring of the production of conjugated dienes in
      the reaction medium. TBARS production, a parameter of lipid peroxidation, was
      also evaluated. In both in vitro systems, only 5-methyltetrahydrofolic acid was
      able to decrease TBARS production in a concentration-dependent manner,
      independently of the presence or absence of homocysteine. In the copper-induced
      LDL oxidation system, vitamin B-12 and 5-methyltetrahydrofolic acid increased the
      lag time of conjugated diene production by 25 and 47%, respectively, suggesting
      that both vitamins in this system had antioxidant properties. Folic acid was
      unable to show antioxidant properties when included in either in vitro system.
      The results demonstrate that 5-methyltetrahydrofolic acid and vitamin B-12 are
      important protective agents against LDL oxidative modifications.

PMID- 15957248
TI  - p53: twenty five years understanding the mechanism of genome protection.
AB  - This year the p53 protein, also known as "guardian of the genome", turns twenty
      five years old. During this period the p53 knowledge have changed from an initial
      pro-oncogene activity to the tumorsupressor p53 function. p53 is activated upon
      stress signals, such as gamma irradiation, UV, hypoxia, virus infection, and DNA
      damage, leading to protection of cells by inducing target genes. The molecules
      activated by p53 induce cell cycle arrest, DNA repair to conserve the genome and
      apoptosis. The regulation of p53 functions is tightly controlled through several
      mechanisms including p53 transcription and translation, protein stability, post
      translational modifications, and subcellular localization. In fact, mutations in
      p53 are the most frequent molecular alterations detected in human tumours.
      Furthermore, in some degenerative processes, fragmentation and oxidative damage
      in DNA take place, and in these situations p53 is involved. So, p53 is considered
      a pharmacological target, p53 overexpression induces apoptosis in cancer and its
      expression blockage protects cells against lethal insults.

PMID- 15957252
TI  - Dietary conjugated linoleic acid increases endurance capacity and fat oxidation
      in mice during exercise.
AB  - Ingestion of CLA activates beta-oxidation and causes loss of body fat in rodents.
      We investigated the effects of dietary CLA on endurance capacity and energy
      metabolism during exercise in mice. Five-week-old male BALB/c mice were fed a
      control diet containing 1.0% linoleic acid or a diet containing 0.5% CLA that
      replaced an equivalent amount of linoleic acid for 1 wk. The maximum swimming
      time until fatigue was significantly higher in the CLA-fed group than in the
      control group. During treadmill running, the respiratory exchange ratio was
      significantly lower in the CLA-fed group, but oxygen consumption did not differ
      significantly between groups, suggesting that FA contributed more as an energy
      substrate in the CLA-fed mice. The muscle lipoprotein lipase activity was
      significantly higher in the CLA-fed group than in the control group. These
      results suggest that CLA ingestion increases endurance exercise capacity by
      promoting fat oxidation during exercise.

PMID- 15957253
TI  - Size and number of lymph particles measured by a particle sizer during absorption
      of structured oils in rats.
AB  - Chylomicrons transport absorbed fat from the intestine to the circulation. During
      dietary fat absorption, the chylomicrons become larger in diameter, and in some
      studies an increase in chylomicron number has been observed as well. In the
      present study, we compared particle size and number in rat lymph following
      administration of four different oils. We administered fish oil, medium-chain TAG
      (MCT), and two structured oils differing in intramolecular structure, with either
      medium-chain FA in the outer positions of the TAG and long-chain n-3 PUFA in the
      sn-2 position (MLM oil) or with the reverse structure (LML oil), to lymph
      cannulated rats and collected lymph in fractions for the following 8 h.
      Chylomicron size was measured by a particle size analyzer immediately after
      collection, and from these data the number of chylomicrons present was estimated.
      The number of particles in lymph increased during the absorption of oils
      containing long-chain PUFA (MLM, LML, and fish oil), whereas it was not affected
      by administration of MCT. The FA from MCT were probably absorbed via the portal
      vein; therefore, only a small number of particles were measured in lymph. When
      comparing the two structured oils, we observed a tendency toward a higher number
      of particles after LML administration, although the difference was not
      statistically significant. The highest number of particles after administration
      of all oils was observed in the size intervals 53-80 and 80-121 nm and probably
      represented small chylomicrons. Thus, the FA composition influenced the number of
      particles in lymph during absorption, whereas TAG structure had only a minor
      influence.

PMID- 15957249
TI  - Astonishing diversity of natural surfactants: 2. Polyether glycosidic ionophores
      and macrocyclic glycosides.
AB  - Polyether glycosidic ionophores and macrocyclic glycosides are of great interest,
      especially for the medicinal and pharmaceutical industries. These biologically
      active natural surfactants are good prospects for the future chemical preparation
      of compounds useful as antibiotics, anticancer agents, or in industry. More than
      300 interesting and unusual natural surfactants are described in this review
      article, including their chemical structures and biological activities.

PMID- 15957254
TI  - Metabolites of dietary triacylglycerol and diacylglycerol during the digestion
      process in rats.
AB  - The present study investigated the metabolic fate of dietary TAG and DAG and also
      their digestion products in the stomach and small intestine. A diet containing
      10% TAG or DAG oil, enriched in 1,3-DAG, was fed to Wistar rats ad libitum for 9
      d. After 18 h of fasting, each diet was re-fed ad libitum for 1 h. The weights of
      the contents of the stomach and small intestine were measured, and the
      acylglycerol and FFA levels were analyzed by GC at 0, 1, and 4 h after the 1-h re
      feeding. The amounts of re-fed diet ingested and the gastric and small intestinal
      content were not different between the two diet groups. In the TAG diet group,
      the main products were TAG and DAG, especially 1(3),2-DAG. In addition, 1,3-DAG
      and 1(3)-MAG were present in the stomach, and the 1,3-DAG levels increased over
      time after the re-feeding period. In the DAG diet group, the main products in the
      stomach were DAG, MAG, FFA, and TAG. There were significantly greater amounts of
      1,3-DAG, 1(3)-MAG, and FFA in the DAG diet group in the stomach compared with the
      TAG diet group. The amount of FFA in the stomach relative to the amount of
      ingested TAG plus DAG in the DAG diet group was higher than that in the TAG diet
      group. Acylglycerol and FFA levels were considerably lower in the small intestine
      than in the stomach. These results indicate that, in the stomach, where acyl
      migration might occur, the digestion products were already different between TAG
      and DAG oil ingestion, and that DAG might be more readily digested by lingual
      lipase compared with TAG. Furthermore, almost all of the dietary lipid was
      absorbed, irrespective of the structure of the acylglycerol present in the small
      intestine.

PMID- 15957255
TI  - Tissue-dependent alterations in lipid mass in mice lacking glycerol kinase.
AB  - Glycerol kinase (ATP:glycerol-3-phosphotransferase, EC 2.7.1.30, glycerokinase)
      (Gyk) has a central role in plasma glycerol extraction and utilization by tissues
      for lipid biosynthesis. Gyk deficiency causes various phenotypic changes ranging
      from asymptomatic hyperglycerolemia to a severe metabolic disorder with growth
      and psychomotor retardation. To better understand the potential role of Gyk in
      tissue lipid metabolism, we determined phospholipid (PL), cholesterol (Chol), and
      triacylglycerol (TG) mass in a number of tissues from mice lacking Gyk. We report
      a tissue-dependent response to Gyk gene deletion. Tissues with elevated total PL
      mass (brain, kidney, muscle) were characterized by the increased mass of
      ethanolamine glycerophospholipids (EtnGpl), choline glycerophospholipids, and
      phosphatidylserine (PtdSer). In heart, lipid changes were characterized by a
      reduction in total PL, including decreased EtnGpl, phosphatidylinositol, and
      PtdSer mass and decreased TG and FFA mass. In parallel with tissue PL
      alterations, tissue Chol was also changed, maintaining a normal Chol/PL ratio.
      Under conditions of Gyk deficiency, we speculate that glycerol-3-phosphate and
      lipid production is maintained via alternative biosynthesis, including
      glycolysis, glyceroneogenesis, or by direct acylation of glycerol in brain,
      muscle, kidney, and liver, but not in heart.

PMID- 15957256
TI  - Vaccenic acid metabolism in the liver of rat and bovine.
AB  - Hepatic metabolism of vaccenic acid (VA), especially its conversion into CLA, was
      studied in the bovine (ruminant species that synthesizes CLA) and in the rat
      (model for non-ruminant) by using the in vitro technique of liver explants. Liver
      tissue samples were collected from fed animals (5 male Wistar rats and 5
      Charolais steers) and incubated at 37 degrees C for 17 h under an atmosphere of
      95% O2/5% CO2 in medium supplemented with 0.75 mM of FA mixture and with 55
      microM [1-14C]VA. VA uptake was about sixfold lower in bovine than in rat liver
      slices (P< 0.01). For both species, VA that was oxidized to partial oxidation
      products represented about 20% of VA incorporated by cells. The chemical
      structure of VA was not modified in bovine liver cells, whereas in rat liver
      cells, 3.2% of VA was converted into 16:0 and only 0.33% into CLA. The extent of
      esterification of VA was similar for both animal species (70-80% of incorporated
      VA). Secretion of VA as part of VLDL particles was very low and similar in rat
      and bovine liver (around 0.07% of incorporated VA). In conclusion,
      characteristics of the hepatic metabolism of VA were similar for rat and bovine
      animals, the liver not being involved in tissue VA conversion into CLA in spite
      of its high capacity for FA desaturation especially in the rat. This indicates
      that endogenous synthesis of CLA should take place exclusively in peripheral
      tissues.

PMID- 15957257
TI  - Anticancer activity and possible mode of action of 4-O-podophyllotoxinyl 12
      hydroxyl-octadec-Z-9-enoate.
AB  - 4-O-Podophyllotoxinyl 12-hydroxyl-octadec-Z-9-enoate (PHEFE) is a structurally
      novel FA analog of podophyllotoxin. In the present study, in vitro effects of
      PHEFE on a panel of 60 human tumor cell lines and its potential modes of
      anticancer action were investigated. PHEFE exhibited strong growth-inhibitory
      action in a number of solid tumor cells in vitro. It did not inhibit tubulin
      polymerization as podophyllotoxin does; rather, it inhibited the catalytic
      activity of topoisomerase II. Flow cytometry and staining assay with 4,6
      diamidine-2-phenylindole dihydrochloride showed that PHEFE blocked the cell cycle
      at the G2/M phase and induced apoptosis in HL-60 cells. These analyses suggest
      that PHEFE has promising anticancer characteristics that differ from
      podophyllotoxin and etoposide.

PMID- 15957258
TI  - Distribution of polyunsaturated fatty acids including conjugated linoleic acids
      in total and subcellular fractions from healthy and cancerous parts of human
      kidneys.
AB  - Differences in the FA composition of subcellular fractions from healthy and
      cancerous kidney tissues from the same patients were examined. Only minor
      differences in CLA content were found between the healthy and the cancerous
      tissue portions. Regarding the distribution pattern, CLA incorporation into
      nuclei and cytosol was significantly higher than incorporation into plasma
      membranes and mitochondria, which could be correlated to the neutral lipid
      content of these fractions. The subcellular distribution pattern of CLA was
      similar to that observed with monounsaturated FA but unlike that found with 18:2n
      6, which underlines the different physiological properties of CLA and 18:2n-6.
      Because PUFA have been suggested to have an effect on cancer risk, the contents
      of n-3 and n-6 PUFA were determined in kidney and renal cell carcinoma (RCC). The
      18:2n-6 content and delta5 desaturase activity were significantly lower, and the
      18:3n-6, 20:3n-6, and 20:5n-3 contents and delta6 desaturase activity were
      significantly higher in RCC than in healthy renal tissue, indicating a changed
      PUFA metabolism in RCC. Previous research has suggested that CLA inhibits the
      elongation and desaturation of 18:2n-6 into 20:4n-6. In that case, one might
      speculate that a diet enriched in CLA would be a useful tool in preventing RCC.
      However, the involvement of CLA in preventing renal cancer could not be
      demonstrated definitively from the design of this experiment. Further
      understanding of the cause and/or consequence of the difference in FA metabolism
      may lead to a better understanding of RCC.

PMID- 15957259
TI  - Identification of delta7 phytosterols and phytosteryl glucosides in the wood and
      bark of several Acacia species.
AB  - The wood and bark of four Acacia species growing in Portugal, namely, A.
      longifolia, A. dealbata, A. melanoxylon, and A. retinodes, were investigated for
      their sterol content. The lipids fractions of the different wood and bark samples
      were isolated, and the sterols were identified and quantified by GC-MS. Two
      delta7 sterols, specifically, spinasterol and dihydrospinasterol, were the main
      sterols found in considerable amounts, particularly in wood tissues (more than
      0.5 g/kg of dry wood in the case of A. melanoxylon and A. retinodes). The
      corresponding unusual steryl glucosides were also identified in significant
      amounts in the wood and bark extracts.

PMID- 15957260
TI  - Foam fractionation of exo-lipases from a growing fungus (Pleurotus sapidus).
AB  - Active lipases were isolated from the culture supernatant of the basidiomycetous
      fungus Pleurotus sapidus by foam fractionation. The pH value, the gas flow, and
      the foaming period were systematically varied to optimize the transport of the
      enzymes into the foam phase. On a 70-mL scale, a maximum recovery of hydrolytic
      activity of 95% was obtained at pH 7.0 and 60 mL N2 min(-1) after 50 min. The
      procedure, with minor modifications, was also applicable to native pellet
      cultures of P. sapidus. The same recovery of 95% was achieved, with purification
      and enrichment factors of 11.6 and 28.0, respectively.

PMID- 15957261
TI  - Bisphosphonates, cancer, and osteonecrosis--a single practice experience.
AB  - Intravenous bisphosphonates have come into increasing use to protect cancer
      patients from adverse boney events. The prevalence of use, demographics of a
      treatment population, and occurrence of a particular side effect are explored in
      this article.

PMID- 15957262
TI  - The role of the hospital then and now.

PMID- 15957263
TI  - 'Radiology' piece a well written synopsis.

PMID- 15957264
TI  - Values based decision making in healthcare: introduction.

PMID- 15957265
TI  - Values based decision making: organizational mission and integrity.

PMID- 15957266
TI  - Values based decision making: a tool for achieving the goals of healthcare.
AB  - The recognition that the success of the healthcare organization depends on its
      achievement of two interrelated goals is a relatively recent phenomenon. In its
      mid-history the healthcare organization was largely able to ignore cost issues.
      In its latter history, many would argue that it ignored its quality goals as it
      pursued its cost goals (15). Either approach, given declining revenues and a
      competitive landscape, is incompatible with continued responsible operation. If
      this is true, then tools that were appropriate when the healthcare organization
      was focused on the achievement of one or another of these goals are not adequate
      as the healthcare organization seeks to achieve both goals together. Thus, new
      perspectives and new tools must be found that help the organization address two
      intimately related but sometimes conflicting goals. Values based decision-making
      can be the perspective needed, and organization ethics is one tool that can be of
      use in supporting it within the institution. But there are caveats. In order for
      values based decision-making to be effective, leadership must take an active role
      in promoting its use. It must relinquish a degree of control and it must begin to
      trust its stakeholders to make decisions within the context of the organization's
      values and goals. This can be extremely difficult, as control by senior
      management is often seen as the only effective means of ensuring that correct
      decisions are made. There are additional difficulties in the healthcare
      organization. Control rests within two groups and the healthcare organization is
      operating in an environment in which variance elimination is emphasized as a
      means of controlling costs. This may be an appealing notion for revenue strapped
      healthcare organization leaders, but it implies greater control exerted by
      managers, not less. Relinquishing any degree of control is a frightening
      prospect, but it has been done successfully. An excellent example of leadership
      encouraging decisions based on values was presented by a unit administrator
      frustrated by the hierarchical structure and ponderous rituals of a traditional
      intensive care unit. Invoking a management tool called "the balanced scorecard"
      (which recognizes the multiplicity of goals and values in any organization) he
      identified the goals and values of the unit, and with the help and input of his
      staff he restructured it into functional multidisciplinary "teams" organized
      around tasks and goals which were based on values. The transformation of
      identities of unit members from their job description to their accomplishments
      improved both the efficiency of the unit and its morale--as well as resulting in
      cost savings. In this example teams had to learn to work together, collaborate
      and disregard the fear of doing things differently. Staff had to be motivated and
      feedback was necessary to ensure goals rather then rules were being meet. The
      balanced scorecard was implemented with mechanisms to support the communication
      and collaboration necessary to achieve the goals of the unit. The experiment was
      successful, but only because leadership recognized that multiple goals and
      multiple values were involved, that were explicitly articulated with the priority
      of excellent care. But once leadership was sure that "shared vision" existed
      leadership was able to trust staff to make appropriate decisions to realize that
      vision.

PMID- 15957267
TI  - Moral distress in healthcare practice: the situation of nurses.

PMID- 15957268
TI  - Bioethics, religion, and democratic deliberation: policy formation and embryonic
      stem cell research.

PMID- 15957270
TI  - Your first choice for publishing original work.

PMID- 15957269
TI  - Informed consent law, ethics, and practice: from infancy to reflective
      adolescence.

PMID- 15957271
TI  - Evidence-based radiology problems: transgluteal approach for percutaneous
      drainage of a deep pelvic abscess.

PMID- 15957272
TI  - Health Canada device licensing cripples Canadian research.

PMID- 15957273
TI  - Computed tomographic features of afferent loop syndrome: pictorial essay.
AB  - ALS, a rare condition, is often difficult to diagnose clinically but has a
      characteristic CT appearance as a U-shaped, fluid-filled tubular structure
      crossing the midline between the abdominal aorta and the superior mesenteric
      artery. Radiologists should be familiar with this rare entity, as awareness of
      its pathognomonic CT features will aid in establishing the correct diagnosis as
      well as in offering a tentative etiology as a guide for treatment.

PMID- 15957274
TI  - Can diagnostic imaging reliably predict the need for surgery in small bowel
      obstruction? Critically appraised topic.

PMID- 15957275
TI  - Ten years of breast screening in the Nova Scotia Breast Screening Program, 1991
      2001. experience: use of an adaptable stereotactic device in the diagnosis of
      screening-detected abnormalities.
AB  - OBJECTIVE: To evaluate and present 10-year outcomes of the Nova Scotia Breast
      Screening Program (NSBSP), a population-based screening program in the province
      of Nova Scotia, Canada, total population 900 000. SETTING: Organized Breast
      Screening Program in Nova Scotia, Canada. METHODS: Rates of participation,
      abnormal referrals, cancer detection rates, and benign:malignant (B:M) rates for
      core biopsy and surgical biopsy were calculated for asymptomatic women receiving
      a mammogram through the NSBSP 1991-2001. RESULTS: Of 192 454 mammograms performed
      on 71 317 women, 33% were aged 40 to 49 years, 39% aged 50 to 59 years, 23% aged
      60 to 69 years, and 5% aged 70 years and over. Cancer detection rate increased in
      each age group respectively: 3.7, 5.8, 9.7, and 13.5 per 1000 population on first
      time screens. The positive predictive value of an abnormal screen increased with
      increasing age groups. Benign breast surgery decreased with increased use of
      needle core breast biopsy (NCBB). Open surgery decreased from 25 to 6 surgeries
      per 1000 screens. Of 1519 open surgical procedures (1328 women), 878 cancers were
      removed, with 37% 10 mm or less, and 61% 15 mm or less. In 613 women in whom the
      node status was assessed, 79% were negative. CONCLUSION: A quality screening
      program incorporating NCBB in the diagnostic work-up is effective in the early
      detection of breast cancer and results in less open surgery, particularly in
      younger women.

PMID- 15957276
TI  - Change in patient doses from radiological examinations at the Vancouver General
      Hospital, 1991-2002.
AB  - OBJECTIVE: Much concern has been expressed over the radiation doses and potential
      harm from x-ray examinations. However, there have been few longitudinal studies
      in North America. A survey of doses from radiological examinations in Canada was
      last carried out in 1995. This study was undertaken to estimate the change in the
      number of patient examinations and patient dose since this last Canadian survey.
      METHODS: The number of radiological examinations and numbers of patients for the
      years 1991 to 2002 were obtained from workload statistics, which are reported to
      the Canadian government each year. Radiological examinations were of the
      following type: general, gastrointestinal or genitourinary, angiography, and
      computed tomography (CT). Average doses were calculated for each group of
      examinations. RESULTS: From 1991 to 2002 there was an increase of 28% in the
      total number of x-ray examinations performed. The proportion of most types of
      examination has stayed fairly constant, except for CT, which has increased
      fourfold in the last 8 years. The striking change is the increased contribution
      to patient effective dose from CT since 1996, these examinations now comprising
      nearly 60% of the total patient dose. The average annual effective dose per
      patient has nearly doubled-from 3.3 mSv in 1991 to 6.0 mSv in 2002. CONCLUSION:
      This paper provides a simple method for any Canadian hospital to estimate the
      radiation dose to its patients. At the Vancouver General Hospital (VGH), the
      number of patient examinations has increased by 28%, but the average annual
      patient effective dose has almost doubled. CT is now by far the largest
      contributor to patient dose in diagnostic radiology. Efforts need to be made to
      reduce patient dose by such methods as reduction in unnecessary exams,
      substitution of nonionizing techniques where possible, and optimization of dose.

PMID- 15957277
TI  - The zero-wall puncture: a novel angiographic puncture technique with substantial
      benefits.

PMID- 15957278
TI  - Answer to case of the month # 99 scimitar syndrome.

PMID- 15957279
TI  - Answer to case of the month # 100 trigeminal schwannoma.

PMID- 15957280
TI  - Re: "Inappropriate distribution of magnetic resonance imaging resources in
      Ontario".

PMID- 15957281
TI  - The pouch of "ducklas".

PMID- 15957282
TI  - Leaders emphasize basics in light of flu vaccine shortage.

PMID- 15957283
TI  - Electronic eyes open. Improving and enhancing resident safety.

PMID- 15957284
TI  - Pain management. Lessons from the field.

PMID- 15957285
TI  - See you in court? Settling 'frivolous' suits has other costs.

PMID- 15957286
TI  - Seven deadly sins nonprofits need to avoid.

PMID- 15957287
TI  - Serving holiday traditions. It's not just about the food.

PMID- 15957289
TI  - Alternative lifestyles in LTC.

PMID- 15957288
TI  - The seven 'I's of fundraising. Building from the basics.

PMID- 15957291
TI  - CCRC developments with strong roots.

PMID- 15957290
TI  - Rock steady independent living.

PMID- 15957292
TI  - The vegetarian option: cost-effective and healthy.

PMID- 15957293
TI  - Get more from your web site.

PMID- 15957294
TI  - Philanthropy: a capital idea.

PMID- 15957295
TI  - Business as usual.

PMID- 15957296
TI  - CLTC study shows accreditation losing its value.

PMID- 15957298
TI  - Skilled nursing facilities. Advice from the experts.

PMID- 15957297
TI  - Ventas expects 2005 court date in $186M suit against law firm.

PMID- 15957299
TI  - Neither here nor there; unique challenges for LTC.

PMID- 15957300
TI  - Building markets for alternative facilities.

PMID- 15957301
TI  - Build a better LTC Web site: move beyond brochureware.

PMID- 15957302
TI  - Realizing miracle major gifts to transform a facility.

PMID- 15957303
TI  - The art of bioethics.

PMID- 15957304
TI  - Pharma PR or medical education?

PMID- 15957305
TI  - Pharma PR or medical education?

PMID- 15957306
TI  - Pharma PR or medical education?

PMID- 15957307
TI  - Pharma PR or medical education?

PMID- 15957308
TI  - FDA and the life-sciences industry: business as usual?".

PMID- 15957309
TI  - What's in a name? Bioethics--and human rights--at UNESCO.

PMID- 15957310
TI  - A measure of success.

PMID- 15957311
TI  - Fast and supersized: is the answer to diet by fiat?

PMID- 15957312
TI  - The curious saga of Congress, the NIH, and conflict of interest.

PMID- 15957313
TI  - The medical malpractice insurance crisis, again.

PMID- 15957314
TI  - Nurses, medical errors, and the culture of blame.

PMID- 15957315
TI  - Rethinking disorders of consciousness: new research and its implications.

PMID- 15957316
TI  - Stem cells, biotechnology, and human rights: implications for a posthuman future.

PMID- 15957317
TI  - Conscientious autonomy: displacing decisions in health care.

PMID- 15957318
TI  - Dead sperm donors or world hunger: are bioethicists studying the right stuff?

PMID- 15957319
TI  - A challenge for tomorrow's leaders.

PMID- 15957320
TI  - Food safety knowledge and behavior of emergency food relief organization workers:
      effects of food safety training intervention.
AB  - The food safety knowledge and food-handling behaviors of 267 volunteer and staff
      workers in emergency food relief organizations in western New York State were
      assessed before and after food safety training. Training was voluntary and
      emphasized basic food safety and prevention of foodborne illness. Results from
      the pre-test showed major gaps in the knowledge and behaviors of those working
      with physically vulnerable populations in emergency food services. These gaps,
      particularly failure to use food thermometers and unsafe use of hands, could lead
      to outbreaks of foodborne disease. Independent-samples t-tests, used to compare
      pre- and post-test scores, indicated that workers' knowledge and reported
      behaviors significantly improved followin good safety training (p < .0001). There
      is a need for relevant and ongoing food safety education in this group.

PMID- 15957321
TI  - Use of focus groups for the environmental health researcher.
AB  - Qualitative research techniques, such as focus groups, are often underutilized by
      the environmental health researcher. Researchers can use the data from focus
      groups for study planning and implementation, as well as the interpretation of
      study results. Focus group data can also be used to understand community risk
      perceptions and potential barriers to co munity acceptance of programs and
      policies. This paper describes the value of focus groups for the environmental
      health researcher. Examples from the literature are inccorporated to demonstrate
      the effective use of focus groups in a variety of environmental health research
      settings. A brief review of data analysis approaches, including commercially
      available software, is provided. The authors encourage increased application of
      this and other qualitative research methods in environmental health research.

PMID- 15957322
TI  - Struck-by-lightning deaths in the United States.
AB  - The objective of the research reported here was to examine the epidemiologic
      characteristics of struck-by-lightning deaths. Using data from both the National
      Centers for Health Statistics (NCHS) multiple-cause-of-death tapes and the Census
      of Fatal Occupational Injuries (CFOI), which is maintained by the Bureau of Labor
      Statistics, the authors calculated numbers and annualized rates of lightning
      related deaths for the United States. They used resident estimates from
      population microdata files maintained by the Census Bureau as the denominators.
      Work-related fatality rates were calculated with denominators derived from the
      Current Population Survey of employment data. Four illustrative investigative
      case reports of lightning-related deaths were contributed by the New Mexico
      Office of the Medical Investigator. It was found that a total of 374 struck-by
      lightning deaths had occurred during 1995-2000 (an average annualized rate of
      0.23 deaths per million persons). The majority of deaths (286 deaths, 75 percent)
      were from the South and the Midwest. The numbers of lightning deaths were highest
      in Florida (49 deaths) and Texas (32 deaths). A total of 129 work-related
      lightning deaths occurred during 1995-2002 (an average annual rate of 0.12 deaths
      per million workers). Agriculture and construction industries recorded the most
      fatalities at 44 and 39 deaths, respectively. Fatal occupational injuries
      resulting from being struck by lightning were highest in Florida (21 deaths) and
      Texas (11 deaths). In the two national surveillance systems examined, incidence
      rates were higher for males and people 20-44 years of age. In conclusion, three
      of every four struck-by-lightning deaths were from the South and the Midwest, and
      during 1995-2002, one of every four struck-by-lightning deaths was work-related.
      Although prevention programs could target the entire nation, interventions might
      be most effective if directed to regions with the majority of fatalities because
      they have the majority of lightning strikes per year.

PMID- 15957323
TI  - Mass gathering preparedness: the experience of the Athens 2004 Olympic and Para
      Olympic Games.
AB  - Planning for environmental health management of the Athens 2004 Olympic Games
      included assessment of the capacity and deficiencies of relevant public health
      agencies in Athens and the other four Olympic cities with 17 detailed
      questionnaires. Different estimates of the expected number of visitors were made
      on the basis of experience from previous Olympic Games. Potential public health
      risks were identified and prioritized. A number of deficiencies in personnel,
      resources, training, and coordination were identified in most agencies. One
      hundred and ninety-six environmental health inspectors were expected to work
      during the Olympic period. Around 18,000 athletes and escorts from 201 countries
      were expected to participate in the Olympic Games and 7,000 to participate in the
      Para-Olympic Games. Three different scenarios regarding the number of expected
      visitors were explored; the most probable estimate being 1,950,000 visitors.
      Foodborne diseases, waterborne diseases, and heat-related illnesses were
      considered of high priority during the Olympic period, as were traffic accidents.
      The Olympic Games are a difficult assignment that demands extensive planning,
      appropriate resources, and timely reporting and coordination among the various
      public health agencies.

PMID- 15957324
TI  - Mean street, U.S.A: the problem of abuse and violence in the field.

PMID- 15957325
TI  - NEHA's Radon/Indoor Air Quality program.

PMID- 15957326
TI  - "When science crosses politics, I: the case of naturally occurring asbestos".

PMID- 15957327
TI  - A special NEHA benefit.

PMID- 15957328
TI  - Rare but deadly. Some simple, cheap blood tests could save thousands of kids'
      lives every year.

PMID- 15957329
TI  - Hunting for health: patients are searching for more medical info online.

PMID- 15957330
TI  - The house call redux.

PMID- 15957331
TI  - Take with a grain of salt.

PMID- 15957332
TI  - Deadly perfectionism?

PMID- 15957333
TI  - Second-guessing Terri Schiavo's doctors (and other Capitol Hill outrages).

PMID- 15957334
TI  - How to code for the new Medicare benefit.

PMID- 15957335
TI  - When a salary guarantee expires.

PMID- 15957336
TI  - It's fun to go to work again.

PMID- 15957337
TI  - If your colleague's a thief.

PMID- 15957338
TI  - 1 doctor, 0 staff.

PMID- 15957339
TI  - How to handle no-shows.

PMID- 15957340
TI  - A no-show showdown letter.

PMID- 15957341
TI  - If an attorney wants a "friendly chat".

PMID- 15957342
TI  - There ought to be a law.

PMID- 15957343
TI  - A clash of ethos.

PMID- 15957344
TI  - Training programs of maxillo-facial and oral surgery.

PMID- 15957345
TI  - A review of paediatric maxillofacial injuries--a hospital-based study.
AB  - This study describes the patient profile with maxillofacial injuries attending a
      trauma unit at a children's hospital. A retrospective record-based analysis was
      carried out of children (less than 13 years of age) presenting with maxillofacial
      injuries from January 1991 to December 2001. Of the almost 90,000 trauma records,
      13% of children presented with maxillofacial injuries. 60% were boys, with a
      quarter less than 3 years of age. Most presented with superficial lacerations and
      abrasions. The face (other than the facial bones) and the mouth/oropharnyx were
      most often injured. Injuries were mainly caused by falls from a variety of
      heights and transport-related injuries. Almost 60% of traffic-related injuries
      involved children as pedestrians being struck by a motor vehicle and 20% were
      cycle-related. Almost 70% of injuries occurred in or around their own home.
      Maxillofacial injuries in children are a significant cause of morbidity and its
      prevention especially in the home and streets needs urgent attention.

PMID- 15957346
TI  - Immunolocalization of fibroblast growth factor-2 (FGF-2) during embryonic
      development of the rat submandibular gland.
AB  - Morphogenesis and cytodifferentiation of the salivary glands are dependent on
      epithelio-mesenchymal interactions, which are mediated either by direct
      intercellular contacts or by the expression of signaling molecules. One of these
      signaling molecules, fibroblast growth factor (FGF), is known to play a crucial
      role in embryonic cell proliferation, cell differentiation and cell migration.
      FGF-2 has been identified as a factor facilitating neoplastic progression in
      salivary glands in humans. The aim of this study was to elucidate the spatial and
      temporal expression of fibroblast growth factor-2 (FGF-2) in the developing rat
      submandibular gland. Submandibular glands were removed from foetal rats on days
      E14.5, 15.5, 16.5, 18.5 and 19.5. Immunolocalization utilizing an antibody to FGF
      2 was performed on sections of the submandibular gland at all the derived stages.
      Diffuse and faint immunolocalization of FGF-2 was seen in the epithelium and
      mesenchyme of the submandibular gland on days E14.5, E15.5 and E16.5. Intense
      immunoreactivity for FGF-2 was observed in epithelial components of the gland
      i.e. in the differentiating acini and ducts, on day E18.5, while on day E19.5,
      the signal was again less intense. These observations suggest that FGF-2 may play
      a specific role in cytodifferentiation of the submandibular gland at a particular
      stage of development.

PMID- 15957347
TI  - Concepts to elucidate the pattern-associated analysis of tooth marks in court.
AB  - Increased awareness by crime scene detectives has led to a rise in number of bite
      mark associated cases appearing before the South African courts. This has led to
      an increased number of dentists being subpoenaed to give forensic evidence. The
      purpose of this paper was to elucidate the presentation of evidence in pattern
      associated tooth mark analysis. Three aspects are discussed. They are the basic
      principle of pattern association, the effects of limited shrinkage and distortion
      on the pattern of the tooth marks, and finally how to overcome the difficulties
      that court personnel experience in visualising bite marks. The author has applied
      these basic concepts over the past six years. Judges and defence advocates have
      been able to understand the simple concepts and apply them to the more complex
      issues before them. The concepts described should be familiar to all dentists and
      forensic odontologists giving tooth mark evidence in the high court. They will
      assist in explaining all aspects of pattern association to the legal fraternity
      and aid in the presentation of the evidence. Their strength is in their
      simplicity.

PMID- 15957348
TI  - Ectopic antral teeth: diagnosis and management implications.

PMID- 15957349
TI  - Nitrous oxide/oxygen conscious sedation without adequate scavenging.

PMID- 15957350
TI  - SARPE in patients affected by bilateral cleft lip and palate deformities.

PMID- 15957351
TI  - The dilemma of student attendance of learning opportunities.
AB  - Lecturers at the School of Dentistry, University of Pretoria, expressed
      dissatisfaction with student attendance of learning opportunities and it was
      suggested that attendance of learning opportunities should be made compulsory.

PMID- 15957352
TI  - General practitioner's radiology. Case 29.

PMID- 15957353
TI  - DoH to ensure PBC aligns with race equality programme.

PMID- 15957354
TI  - Blueprint calls for strong leadership.

PMID- 15957355
TI  - NHS structure. Stuck in the middle and friendless--the lot of an SHA?

PMID- 15957356
TI  - On being patient-focused.

PMID- 15957357
TI  - Data briefing. Using statistics to detect poor practice.

PMID- 15957358
TI  - Good management. Wanna be in my gang?
AB  - PCTs are being urged to work together to increase their capacity to negotiate
      effectively with acute trusts. In Manchester a collaboration of 14 PCTs has
      enjoyed considerable success, with member trusts sharing a statement of strategic
      intent. The experience the Manchester PCTs suggests collaborations of this type
      are more effective when not driven by SHAs or central legislation.

PMID- 15957359
TI  - Clinical management. Stroke of genius.

PMID- 15957360
TI  - Development. Psyched up.

PMID- 15957361
TI  - The quiet revolution. Interview by Lynn Eaton.

PMID- 15957362
TI  - Education. Skills to pay the bills.

PMID- 15957363
TI  - Success stories. Take the plunge.

PMID- 15957364
TI  - Skills agreement. Big deal.

PMID- 15957365
TI  - The effect of Juzen-taiho-to/TJ-48 on the expression of killer-cell
      immunoglobulin-like receptors (CD158a/b) on peripheral lymphocytes in vitro
      experiment.
AB  - Juzen-taiho-to (TJ-48), a mixture of extracts from 10 medicinal herbs, has been
      used traditionally to treat patients with anemia, anorexia or fatigue. It is well
      known that the treatment of TJ-48 result in the decrease of patient's complaints,
      as well as the increase of NK cytolytic activity (NK activity) although its
      augmentation is not clear in the other kampo formula from the clinical viewpoint.
      To investigate its biological activities, such as the augmentation of NK
      activity, we analyzed the effects of TJ-48 on the expression of killer-cell
      immunoglobulin-like receptors (KIRs) in vitro experiment. The peripheral
      lymphocytes were incubated in medium alone, or medium containing TJ-48 or
      interleukin-2 (IL-2) plus TJ-48 at several concentrations for 48 h. After each
      incubation, cells were collected and their KIRs were detected by flow cytometry
      using monoclonal antibodies CD158a and CD158b. TJ-48 increased the populations of
      CD16+CD158a+ and CD16+CD158b+ cells in a dose-dependent manner. In contrast, CD16
      CD158a/b+ cells did not increase. Additionally, the extract of TJ-48 enhanced the
      increase of KIRs expression induced by IL-2. These actions contribute to the
      augmentation of NK cytolytic activity by TJ-48, and might explain, in part, its
      antitumor effects which has been observed in vivo.

PMID- 15957366
TI  - Vasodilative effect of perillaldehyde on isolated rat aorta.
AB  - The vasodilative effect of perillaldehyde, one of the major oil components in
      Perilla frutescens BRITTON, was studied using isolated rat aorta. Perillaldehyde
      at final concentrations of 0.01 to 1 mM showed dose-dependent relaxation of the
      aorta contracted by treatment with prostaglandin F2alpha or norepinephrine.
      Neither the presence of NG-nitro-L-arginine methyl ester nor removal of the
      aortic endothelium affected the vasodilatation, suggesting that perillaldehyde
      exerts a direct effect on vascular smooth muscle cells. The vasodilative effect
      of perillaldehyde was not inhibited by pretreatment with a beta-adrenergic
      receptor blocker (propranolol), an inhibitor of phosphodiesterase (theophylline),
      a delayed rectifier K+ channel blocker (tetraethylammonium chloride), or an ATP
      sensitive K+ channel blocker (glibenclamide). However, perillaldehyde showed
      contrasting effects on vasodilatation of the aorta contracted by an influx of
      extracellular Ca2+ - perillaldehyde caused little vasodilatation on the aorta
      contracted by the Ca2+ ionophore A23187, while it inhibited the vasoconstriction
      induced by treatment with high-concentration K+, which dominantly opened the
      voltage-dependent Ca2+ channel. These results suggest that the vasodilative
      effect of perillaldehyde is derived from blocking the Ca2+ channels.

PMID- 15957367
TI  - Pharmacological assay of Cordia verbenacea V: oral and topical anti-inflammatory
      activity, analgesic effect and fetus toxicity of a crude leaf extract.
AB  - Cordia verbenacea D.C. (Borraginaceae) is a perennial bush plant that grows
      widely along the southeastern coast of Brazil. Its leaves have been used in folk
      medicine for their anti-ulcer, anti-inflammatory and cicatrizing activities. We
      have already described the anti-inflammatory properties of C. verbenacea and its
      low toxicity in different acute animal models. In the present study, we
      investigated the anti-inflammatory activity in sub-chronic animal models of a
      crude leaf lyophilized extract when administered by oral route or topically
      applied, and concomitantly, its analgesic potency and toxicity to the fetus.
      Topical administration of the extract inhibited nystatin-induced edema
      proportionally to the doses used, and this effect at a dose of 4.56 mg/kg body
      wt. was similar to that observed with 6.0 mg/kg body wt. of naproxen. In
      miconazole-induced edema, the leaf extract at a dose of 1.24 mg/kg body wt.,
      orally administered, has a very similar effect as compared to nimezulide (2.5
      mg/kg body wt.) and dexamethasone (0.2 mg/kg body wt.). At an oral dose of 2.48
      mg/kg body wt. the extract showed a very low analgesic effect, and total absence
      of fetus toxicity at doses of less than 7.44 mg/kg body wt.

PMID- 15957368
TI  - Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point
      to an effective antiulcer effect on gastric ulcer models in mice.
AB  - Plant extracts are some of the most attractive sources of new drugs and have
      shown promising results for the treatment of gastric ulcers. Several folk
      medicinal plants and herbs have been used to treat gastrointestinal disorders,
      including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common
      in the diet of the population of northern South America. Our research interest in
      this plant arose because of its potential medicinal value as a tonic and against
      stomachache, as used in folk medicine. In this paper we evaluated three different
      extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from
      M. americana L., for their ability to protect the gastric mucosa against injuries
      caused by necrotizing agents (0.3 M HCl/60% EtOH), hypothermic restraint stress,
      nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation.
      In the HCl/EtOH-induced gastric-ulcer model, EtOH and DCM extracts demonstrated
      significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm)
      and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/
      1.4 mm) (p<0.0001). In the NSAID/cholinomimetic-induced lesion model, both EtOH
      and DCM extracts showed antiulcerogenic effects with significant reduction in the
      damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm),
      respectively, as compared to the control group (13.0 +/- 0.9 mm) (p<0.0001). In
      the gastric ulcer induced by hypothermic-restraint stress, both extracts also
      showed significant activity, and inhibited the gastric lesion index by 58% and
      75%, respectively. The EtOH and DCM extracts also changed gastric juice
      parameters as well as those of cimetidine, decreased gastric acid secretion
      significantly (p<0.0001), increased pH values and promoted reduced acid output
      (p<0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any
      significant antiulcerogenic activity, nor did it change gastric-juice parameters
      (p>0.05). The results suggest that EtOH and DCM extracts obtained from M.
      americana possess excellent antisecretory and/or gastrotective effect in all
      gastric ulcer models. These results suggest that the antiulcerogenic compound(s)
      present in M. americana may be clustered in the apolar fraction, which will be
      investigated by our group for the probable mechanisms of action.

PMID- 15957369
TI  - Berberine inhibits arylamine N-acetyltransferase activity and gene expression in
      mouse leukemia L 1210 cells.
AB  - N-acetyltransferases (NATs) are recognized to play a key role in the primary step
      of arylamine compounds metabolism. Polymorphic NAT is coded for rapid or slow
      acetylators, which are being thought to involve cancer risk related to
      environmental exposure. Berberine has been shown to induce apoptosis and affect
      NAT activity in human leukemia cells. The purpose of this study is to examine
      whether or not berberine could affect arylamine NAT activity and gene expression
      (NAT mRNA) and the levels of NAT protein in mouse leukemia cells (L 1210). N
      acetylated and non-N-acetylated AF were determined and quantited by using high
      performance liquid chromatography. NAT mRNA was determined and quantited by using
      RT-PCR. The levels of NAT protein were examined by western blotting and
      determined by using flow cytometry. Berberine displayed a dose-dependent
      inhibition to cytosolic NAT activity and intact mice leukemia cells. Time-course
      experiments indicated that N-acetylation of AF measured from intact mice leukemia
      cells were inhibited by berberine for up to 24 h. The NAT1 mRNA and NAT proteins
      in mouse leukemia cells were also inhibited by berberine. This report is the
      first demonstration, which showed berberine affect mice leukemia cells NAT
      activity, gene expression (NAT1 mRNA) and levels of NAT protein.

PMID- 15957370
TI  - Effect of the aqueous extract of Hyptis pectinata on liver mitochondrial
      respiration.
AB  - Some studies have indicated that mitochondria may be the target organelle of
      plants. We therefore decided to assess the effects of the aqueous extract of
      Hyptis pectinata leaves on liver mitochondrial respiratory function in vitro.
      Eight rat livers were subjected to isolation of mitochondria by differential
      centrifugation. In an adequate medium, the plant extract was added at different
      concentrations. The analyzed data were: state 3, state 4 and respiratory control
      ratio (RCR). H. pectinata extract caused a statistically significant decrease in
      state 3 (at 0.05, 0.1 and 0.2 mg/mg protein) and RCR (at 0.05, 0.1 and 0.2 mg/mg
      protein). Respiratory state 4 was not altered by the increasing concentrations.
      In conclusion, the aqueous extract of H. pectinata leaves may not injure the
      mitochondrial inner membrane but decreases significantly the oxidative
      phosphorylation.

PMID- 15957371
TI  - Zea mays L. extracts modify glomerular function and potassium urinary excretion
      in conscious rats.
AB  - Diuretic and uricosuric properties have traditionally been attributed to corn
      silk, stigma/style of Zea mays L. Although the diuretic effect was confirmed,
      studies of the plant's effects on renal function or solute excretion were
      lacking. Thus, we studied the effects of corn silk aqueous extract on the urinary
      excretion of water, Na+, K+, and uric acid. Glomerular and proximal tubular
      function and Na+ tubular handling were also studied. Conscious, unrestrained
      adult male rats were housed in individual metabolic cages (IMC) with continuous
      urine collection for 5 and 3 h, following two protocols. The effects of 25, 50,
      200, 350, and 500 mg/kg body wt. corn silk extract on urine volume plus Na+ and
      K+ excretions were studied in water-loaded conscious rats (2.5 ml/100 g body wt.)
      in the IMC for 5 h (Protocol 1). Kaliuresis was observed with doses of 350
      (100.42 +/- 22.32-120.28 +/- 19.70 microEq/5 h/100 g body wt.; n = 13) and 500
      mg/kg body wt. (94.97+/- 29.30-134.32 +/- 39.98 microEq/5h/100 g body wt.; n =
      12; p<0.01), and the latter dose resulted in diuresis as well (1.98 +/- 0.44-2.41
      +/- 0.41 ml/5 h/100 g body wt.; n = 12; p<0.05). The effects of a 500 mg/kg body
      wt. dose of corn silk extract on urine volume, Na+, K+ and uric acid excretions,
      and glomerular and proximal tubular function, were measured respectively by
      creatinine (Cler) and Li+ (ClLi) clearances and Na+ tubular handling, in water
      loaded rats (5 ml/100 g body wt.) in the IMC for 3 h (Protocol 2). Clcr (294.6 +/
      73.2, n = 12, to 241.7 +/- 48.0 microl/ min/100 g body wt.; n = 13; p<0.05) and
      the Na+ filtered load (41.9 +/- 10.3, n = 12, to 34.3 +/- .8, n = 13, p<0.05)
      decreased and ClLi and Na+ excretion were unchanged, while K+ excretion (0.1044
      +/- 0.0458, n=12, to 0.2289 +/- 0.0583 microEq/min/100 body wt.; n = 13; p<0.001)
      increased. For Na+ tubular handling, the fractional proximal tubular reabsorption
      (91.5 +/- 3.5, n = 12, to 87.5 +/- 3.4%; n = 13; p<0.01) decreased, and both
      fractional distal reabsorptions--I and II--increased (96.5 +/- 1.5, n = 12, to
      97.8 +/- 0.9%; n = 13; p<0.01; and 8.2 +/- 3.5, n = 12, to 12.2 +/- 3.4%, n = 13,
      p<0.01, respectively). To summarize, in water-loaded conscious rats (2.5 ml/100
      body wt.), corn silk aqueous extract is diuretic at a dose of 500 mg/kg body wt.
      and kaliuretic at doses of 350 and 500 mg/kg body wt. In water-loaded conscious
      rats (5.0 ml/100 g body wt.), corn silk aqueous extract is kaliuretic at a dose
      of 500 mg/kg body wt., but glomerular filtration and filtered load decrease
      without affecting proximal tubular function, Na+, or uric acid excretion.

PMID- 15957372
TI  - Antifungal constituents of northern prickly ash, Zanthoxylum americanum mill.
AB  - Leaf, fruit, stem, bark and root of Zanthoxylum americanum were investigated for
      antifungal activity with 11 strains of fungi representing diverse opportunistic
      and systemic pathogens, including Candida albicans, Cryptococcus neoformans and
      Aspergillus fumigatus. All extracts demonstrated a broad spectrum of antifungal
      activity and inhibited at least eight fungal species in a disk diffusion assay
      (600 microg/disk). Antifungal activity was light-dependent, with fruit and leaf
      extracts most active in general. The presence of light-mediated compounds, such
      as psoralen, 8-methoxypsoralen and imperatorin in extracts of different organs
      was confirmed by RP-HPLC. A high furanocoumarin content was detected in fruit and
      leaf and low furanocoumarin levels were found in bark and wood. A high positive
      correlation was observed between total furanocoumarin content and fungal
      inhibition zones (r2=0.902, p<0.001). The results provide a phytochemical basis
      for the very widespread use of Z. americanum in indigenous North American
      ethnomedical tradition for conditions that may be related to fungal infections.

PMID- 15957373
TI  - Structure--antimicrobial activity of some natural isocoumarins and their
      analogues.
AB  - Three naturally occurring isocoumarins (paepalantine, paepalantine 9-O-beta-D
      glucopyranoside and paepalantine 9-O-beta-D-allopyranosyl(1 --> 6)
      glucopyranoside) and two semi-synthetic analogues, 9,10-acylated compound and 9
      OH-10-methylated compound, structurally similar to paepalantine, were evaluated
      for antimicrobial activity using a spectrophotometric microdilution technique.
      The paepalantine was active against S. aureus, S. epidermidis, and E. faecalis
      while the other four compounds proved ineffective against all microorganisms
      tested at concentrations of 500 microg/ml. Variations in phenolic substitution at
      OH-9 and/or OH-10 in the paepalantine molecule resulted in compounds without
      antimicrobial activity. A combination of structural features, two phenolic groups
      as cathecolic system, forms an oxygenated system arrangement that may reflect the
      potentially antimicrobial properties of paepalantine.

PMID- 15957374
TI  - Antiprotozoal activity of Brazilian plant extracts from isoquinoline alkaloid
      producing families.
AB  - Leishmaniasis and Chagas disease afflict the poorest countries in the world. The
      Brazilian flora represents a rich source for the screening of potential
      antiparasitic compounds. In this work, we tested the total alkaloid and ethanol
      extracts of nine different plants from Brazilian families which produce
      isoquinoline alkaloids, to determine their in vitro antiparasitic effect against
      L. chagasi and T. cruzi parasites. Promastigotes of L. chagasi were shown to be
      susceptible only to the total alkaloid extracts of A. crassiflora (EC50 value =
      24.89 microg/ml), A. coriacea (EC50 value = 41.60 microg/ml), C. ovalifolia (EC50
      value = 63.88 microg/ml) and G. australis (EC50 value = 37.88 microg/ml). Except
      for the G. australis total alkaloids, all the three extracts presented a
      considerable activity when tested against intracellular amastigotes. The most
      effective alkaloid extracts were those from A. crassiflora and C. ovalifolia,
      which reduced the number of infected macrophages at 25 microg/ml by 86.1% and
      89.8%, respectively. Among the 18 tested extracts, 16 showed anti-Trypanosoma
      activity. Eight extracts (A. crassiflora, A. coriacea, C. ovalifolia, D.
      furfuracea, D. lanceolata, S. guianensis, X. emarginata and G. australis) were
      the most effective against the trypomastigotes, killing approximately 100% of the
      parasites at the maximal concentration of 100 microg/ml. Cytotoxicity against
      mammalian cells was evaluated for all extracts, but potential ones showed little
      or no cytotoxicity and a considerable antiparasitic effect, including D.
      furfuracea, D. lanceolata, G. australis, S. guianensis and X. emarginata. Plants
      are a rich source of natural compounds, and a powerful tool for the development
      of new arsenals for the therapy of protozoan diseases.

PMID- 15957375
TI  - Effect of oleanane triterpenoids from Terminalia arjuna--a cardioprotective drug
      on the process of respiratory oxyburst.
AB  - The oleanane triterpenes arjunic acid, arjungenin and their glucosides, arjunetin
      and arjunglucoside II, were isolated from the bark of Terminalia arjuna.
      Arjungenin and its glucoside exhibited a moderate free radical scavenging
      activity while all the compounds showed no effect on the superoxide release from
      PMN cells. Further arjungenin also exhibited greater inhibitory action on the
      hypochlorous acid production from human neutrophils.

PMID- 15957377
TI  - Veterinarians refine new arbovirus diagnostic tools.

PMID- 15957378
TI  - Members making a difference.

PMID- 15957379
TI  - Corporate social responsibility & animal welfare--a global perspective.

PMID- 15957380
TI  - Practices of excellence in customer service--Greenhills Veterinary Hospital.

PMID- 15957381
TI  - Keniry report recommendations gather momentum.

PMID- 15957382
TI  - Porcine reproductive and respiratory syndrome (PRRS) virus--a significant disease
      of pigs.

PMID- 15957383
TI  - Taking the fight to feral pigs.

PMID- 15957384
TI  - Live export debate--take two!

PMID- 15957385
TI  - Taking stock of Australia's export animal trade.

PMID- 15957386
TI  - Auscultation and echocardiographic findings in Bull Terriers with and without
      polycystic kidney disease.
AB  - OBJECTIVE: To investigate a possible association between Bull Terrier polycystic
      kidney disease (BTPKD) and cardiac disease, to determine the prevalence of mitral
      valve disease (MVD) and left ventricular outflow tract obstruction (LVOTO) in the
      Australian Bull Terrier population, and to compare auscultation and
      echocardiography in detection of cardiac disease in Bull Terriers. DESIGN: Ninety
      nine Bull Terriers, ranging in age from 8 weeks to 13 years and 11 months were
      auscultated and examined using renal ultrasonography; 86 were also examined using
      echocardiography. The prevalence and severity of heart defects in dogs with BTPKD
      was compared with that in dogs without BTPKD. RESULTS: Nineteen of these 99 dogs
      were diagnosed with BTPKD. Forty-two percent of Bull Terriers with BTPKD and 28%
      of those without BTPKD had murmurs characteristic of mitral regurgitation or
      LVOTO. How recently an animal was descended from an ancestor with BTPKD was
      associated with presence (P = 0.008) and loudness of a murmur (P = 0.009).
      Overall, echocardiography detected MVD in 39% of Bull Terriers, with increased
      prevalence in older animals (P = 0.003). Mitral stenosis was found in eight
      cases. Fifty-three percent of dogs in this study had evidence of LVOTO, with
      obstruction consisting of a complex of lesions including dynamic or fixed
      subvalvular LVOTO, significantly narrowed left ventricular outflow tract or
      valvular aortic stenosis. Dogs with BTPKD, or those descended from dogs with
      BTPKD, were more likely to have MVD (P = 0.006), and while LVOTO was not more
      common in these dogs, if they did have LVOTO, they were more likely to have
      severe obstruction than dogs with no ancestors with BTPKD (analysed in three ways
      P = 0.028 to 0.001). In this study, 46% of Bull Terriers without a murmur or
      arrhythmia had cardiac disease detected on echocardiographic examination.
      CONCLUSION: Cardiac disease, especially MVD and LVOTO, was common in Bull
      Terriers in this study, and those with BTPKD had an increased risk of cardiac
      abnormalities. Auscultation did not detect a significant number of Bull Terriers
      with cardiac disease.

PMID- 15957387
TI  - Recurrent flank alopecia in a Tibetan Terrier.
AB  - Recurrent flank alopecia is described in a 2-year-old, male, neutered Tibetan
      Terrier with concurrent atopic dermatitis. The diagnosis of recurrent flank
      alopecia was made after 3 consecutive years of localised, winter-onset alopecia.
      The diagnosis was based on history, compatible clinical signs and supportive
      histopathology. The diagnosis was complicated by the presence of concurrent
      pruritic dermatitis. To our knowledge this is the first report of recurrent flank
      alopecia in this breed.

PMID- 15957388
TI  - Juvenile cellulitis in an 8-month-old dog.
AB  - An 8-month-old, crossbred dog, presented with a painful, swollen face. The
      problem was of 4 weeks duration and had not responded to antibiotics. A diagnosis
      of canine juvenile cellulitis was based on the clinical presentation and
      supportive cytological and histopathological changes. Attempts to identify canine
      distemper virus were not successful. Complete resolution occurred with
      glucocorticoid therapy. This is the first report of canine juvenile cellulitis in
      a dog of this age.

PMID- 15957389
TI  - Cystadenocarcinoma in the ovary of a Thoroughbred mare.

PMID- 15957390
TI  - Fluoroacetate poisoning in seven domestic dogs.

PMID- 15957391
TI  - Snake envenomation in dogs in New South Wales.
AB  - OBJECTIVE: To obtain baseline data on the prevalence of elapid snake envenomation
      in dogs presented to veterinary practices in New South Wales and to assess
      attitudes of veterinarians to this clinical entity. PROCEDURE: A mailed
      questionnaire, sent to all veterinary clinics within New South Wales, was
      utilised to collect epidemiological information regarding elapid snake
      envenomation in dogs. RESULTS: A response rate of 68% was obtained and a yearly
      prevalence of snake envenomation in dogs across New South Wales veterinary
      clinics was estimated as 0.31%. The most common species reported to be
      responsible for envenomation within NSW was the Red Bellied Black snake
      (Pseudechis porphyriacus) followed by the Brown snake (Pseudonaja textilis) and
      then Tiger snake (Notechis scutatus). The reported envenomation syndromes caused
      by these common snake species were perceived to be similar for Brown and Tiger
      snakes but differed for Red Bellied Black snakes. Diagnosis of snake envenomation
      was based predominantly on the recognition of clinical signs. Specific diagnostic
      tests, such as venom detection kits, were used infrequently. The most common
      treatment was reported to be a combination of intravenous fluid therapy and
      antivenom, and monitoring of response to this treatment was usually through
      assessment of clinical signs. Survival after antivenom administration was
      reported to be highest for Red Bellied Black snake species. Survival was
      perceived to be associated with time between envenomation and presentation to the
      veterinary clinic and with antivenom administration. CONCLUSIONS: Current
      attitudes and perceptions of veterinarians have been defined. Diagnosis of
      species-specific snake envenomation is shown to be made on the basis of clinical
      signs which are, however, reported as similar for each species. Clearer
      definition of these envenomation syndromes and identification of accessible
      diagnostic testing procedures are needed.

PMID- 15957392
TI  - Rapid identification of virulence genes in enterotoxigenic Escherichia coli
      isolates associated with diarrhoea in Queensland piggeries.
AB  - OBJECTIVE: To identify virulence genes in enterotoxigenic E coli (ETEC) isolates
      associated with diarrhoea in neonatal, 1 to 3 week-old and weaned pigs in
      southeast Queensland. DESIGN: Multiplex PCR and serotyping were applied to E coli
      isolates obtained over a 5-year period (1998-2002) from cases diagnosed at
      Toowoomba Veterinary Laboratory. PROCEDURE: A total of 126 isolates from 25
      different Queensland piggeries were tested for haemolytic activity on 5% sheep
      blood agar and by multiplex PCR for the presence of five commonly recognised
      fimbrial (F4, F5, F6, F41 and F18) and three enterotoxin genes (STa, STb, LT). A
      subset of 62 representative isolates were serotyped by slide agglutination. For
      comparative purposes, multiplex PCR was also performed on the DNA of 31 ETEC
      isolates from 9 serotypes originating from piggeries in southern New South Wales.
      RESULTS: A total of 113 (89.7%) of the isolates from Queensland possessed ETEC
      virulence genes, including 14 of 15 isolates from neonatal pigs (93.3%), 18 of 23
      isolates from 1 to 3 week old pigs (78.3%) and 81 of 88 isolates from weaned pigs
      (92.1%). F4:STa:STb:LT (serotype O149) was the most prevalent pathotype in
      neonatal and 1-3 week old pigs and F4:STa:STb:LT (serotype O149) and
      F18:STa:STb:LT (serotype O141) were most prevalent in weaned pigs. In comparison,
      isolates obtained from neonatal pigs from New South Wales belonged to a more
      diverse range of pathotypes and serotypes. CONCLUSION: Multiplex PCR was a rapid
      and specific method for detecting the presence of ETEC virulence genes in porcine
      E coli isolates. For isolates obtained from cases of suspected colibacillosis in
      Queensland, growth of a heavy pure culture of haemolytic E coli was a sensitive
      prognostic indicator of the presence of ETEC virulence genes in the isolate. ETEC
      pathotypes and serotypes remained stable in Queensland piggeries over the five
      year study period and appear to have changed little over the last three decades.

PMID- 15957393
TI  - The detection of porcine circovirus in the Australian pig herd.
AB  - OBJECTIVE: To determine if porcine circovirus (PCV) type 1 (PCV1) or type 2
      (PCV2) is present in the Australian pig herd, to conduct preliminary genetic
      characterisation of any viruses detected, and to determine if there is any
      obvious virological reason why post-weaning multisystemic wasting disease (PMWS),
      associated with PCV infection in other countries, has not been detected in
      Australia. DESIGN: Serum samples were collected from 14 randomly selected pig
      farms in Western Australia and used for detection of PCV antibody. Additional
      samples from one farm were obtained at 2-week intervals from pigs between 2 and
      12 weeks of age to detect any age-associated variations in prevalence of
      infection. Veterinary practitioners from four Australian states submitted tissues
      of dead or unthrifty weaned pigs, and these were examined for evidence of PCV1
      and PCV2 infection. PROCEDURE: Sera were tested for antibody to PCV using an
      indirect immunofluorescence assay (IFA). Tissues were tested for PCV1 and PCV2
      genomic material using a multiplex PCR. RESULTS: PCV antibody was detected in
      approximately 30% of Western Australian pigs tested. PCV1 DNA was detected in
      tissue samples from Western Australia, South Australia and New South Wales and
      PCV2 DNA was detected in tissue samples from Western Australia, New South Wales
      and Queensland. Sequence analysis of the PCR products indicated the PCV1 and PCV2
      present in Australia were very similar to strains in other countries where PMWS
      is endemic. CONCLUSION: Both PCV1 and PCV2 are present in Australia and the
      viruses present appear similar to those in countries with PMWS. The absence of
      PCV2-associated PMWS in Australia may be due to absence of essential secondary
      factors required for PCV2 to produce PMWS.

PMID- 15957394
TI  - The effect of interpreting an ELISA at a lower cut-off on detection of clinical
      cases of bovine Johne's disease.

PMID- 15957395
TI  - Mentors, teachers, and experts among us.

PMID- 15957396
TI  - TLC at college of DuPage.

PMID- 15957397
TI  - Faculty matters. Elizabeth Speakman.

PMID- 15957398
TI  - Excellence in teaching end-of-life care: a new multimedia toolkit for nurse
      educators.
AB  - Nursing strongly values comfort and patient-centered care at the end of life, but
      little end-of-life content is included in most basic nursing education programs.
      An innovative way to improve nursing education about the end-of-life transition
      is to provide nurse educators with an electronic toolkit. This article describes
      a newly created multimedia toolkit (TNEEL), which includes engaging strategies
      for teaching and learning about end-of-life care.

PMID- 15957399
TI  - Using critical thinking vignettes to evaluate student learning.
AB  - Nursing skills have traditionally been evaluated using laboratory demonstration.
      The reality, however, is that skill performance does not occur in isolation in
      the practice setting. Nurses demonstrate skills while functioning within several
      nursing roles. Following an examination of the relationship of educational
      outcomes focusing on critical thinking, communication ability, and therapeutic
      nursing interventions, faculty at a two-year associate degree nursing program
      formulated Critical Thinking Vignettes as a method of assessing student outcomes.
      Students role-play a nurse-client interaction using a case study prompt. Student
      performance outcomes in skills demonstration, communication, teaching, problem
      solving, critical thinking, identification of resources, and response to
      environmental cues are evaluated. Preliminary reliability and inter-rater
      reliability studies suggest that this method provides a controlled method of
      assessing nursing outcomes reflective of actual practice.

PMID- 15957400
TI  - Web-based courses. More than curriculum.
AB  - Online program development depends on an educationally and technologically sound
      curriculum supported by a solid infrastructure. Creation of a virtual environment
      through design of online registration and records, financial aid, orientation,
      advisement, resources, and evaluation and assessment provides students with
      access and program integrity.The planning of an academic support system as an
      electronic environment provides challenges and institutional issues requiring
      systematic analysis.

PMID- 15957401
TI  - Learning clinical teaching. Is it magic?
AB  - Clinical teaching in nursing is a complex phenomenon that lacks a coherent
      theoretical base and is perplexing to novices, who tend to teach as they were
      taught. Nursing educators must find strategies to assist novice clinical teachers
      to learn the practice of clinical teaching. This article reports on the findings
      of a qualitative study that describes the process of learning clinical teaching
      through the voices of five novice and five expert clinical teachers. Essential
      differences between novices and experts are presented, and the challenges of
      preparing clinical teachers are discussed.

PMID- 15957402
TI  - Using a faculty evaluation triad to achieve evidence-based teaching.
AB  - Aneffective and comprehensive faculty evaluation system provides both formative
      and summative data for ongoing faculty development. It also provides data for
      annual faculty evaluation and tenure and promotion decision making. To achieve an
      effective system, a triad of faculty evaluation data sources--student ratings,
      teaching portfolio, and peer evaluation--were developed. Concurrently, a system
      of faculty mentorship was implemented, as well as an administrative structure to
      effectively use data to assist in merit pay and promotion decisions. Using a
      comprehensive, evidenced-based system to document, analyze, and improve teaching
      effectiveness is essential to assuring excellence in teaching and learning.

PMID- 15957403
TI  - Enacting narrative pedagogy. The lived experiences of students and teachers.
AB  - Reforming nursing education to meet contemporary challenges in educational and
      clinical environments is needed through the development and implementation of new
      pedagogies. Nancy Diekelmann is advancing the science of nursing education by
      describing a new phenomenological pedagogy, Narrative Pedagogy, identified
      through interpretive research in nursing education. Narrative Pedagogy is an
      approach to reforming nursing education that is always site specific and not
      generalizable from school to school. However, the processes of Narrative Pedagogy
      are transferable and can be enacted in many contexts. This study describes the
      common experiences and shared meanings of teachers and students engaging in or
      enacting Narrative Pedagogy. Diekelmann gathered seven teachers and students in
      five schools of nursing in four midwestern states to share their experiences.
      Interpretive phenomenology was used to analyze the group interview. One of the
      findings identified during this analysis, Enacting Narrative Pedagogy, is
      explicated, and two themes, Decentering Skill Acquisition and Content and
      Attending to the Practices of Thinking, are described.

PMID- 15957404
TI  - [Educational lecture: basis of the "basic physiology"].

PMID- 15957405
TI  - [Hellow, PSJ].

PMID- 15957406
TI  - [Overview: Progress on and trends in the world Protein 3000 Project].

PMID- 15957407
TI  - [Large-scale structural proteomics project at RIKEN: present and future].

PMID- 15957408
TI  - [Progress and maturation of protein crystallographic experiments].

PMID- 15957409
TI  - [Role of NMR in structural proteomics].

PMID- 15957410
TI  - [Attitude of pharmaceutical company toward protein structure analysis].

PMID- 15957411
TI  - [Crystallography-based drug design].

PMID- 15957412
TI  - [Evolution of the vertebrate brain: insights from the lamprey brain development].

PMID- 15957413
TI  - [Regulation of self-renewal of hematopoietic stem cells in the niche].

PMID- 15957414
TI  - [Analysis of retrovirus genome dimerization in virion].

PMID- 15957415
TI  - [Changing pattern of the respiratory function associated with resected lung
      lobe].
AB  - Respiratory function before and 2 months after lung lobectomy was analyzed
      associated with resected lobe. Post- or preoperative ratios of FEV1.0 or VC were
      compared among (1) predicted value by the number of subsegments using
      bronchofiberscopy, (2) predicted value by the lobar volume ratio using computed
      tomography (CT), and (3) actually measured value. Using subsegments method, post-
      or preoperative predicted VC ratios were 85 +/- 1% after right upper lobectomy
      (RU), 69 +/- 1% after right lower lobetomy (RL), 74 +/- 1% after left upper
      lobectomy (LU), and 75 +/- 1% after left lower lobectomy (LL). Using CT method,
      post- or preoperative predicted VC ratios were 80 +/- 2% after RU, 76 +/- 4%
      after RL, 74 +/- 2% after LU, and 79 +/- 3% after LL. Actually measured post- or
      preoperative FEV1.0 ratios were 82 +/- 3% after RU, 89 +/- 8% after RL, 73 +/- 3%
      after LU, and 86 +/- 5% after LL, and the VC ratios were 88 +/- 5% after RU, 79
      +/- 3% after RL, 77 +/- 4% after LU, and 94 +/- 3% after LL. In the FEV1.0
      analysis using both subsegments method and CT method, the predicted value was
      correlated with upper lobectomy but was overestimated in case of lower lobectomy.
      This phenomenon might be caused by the postoperative bronchial branching
      deformity after upper lobectomy. In the VC analysis using subsegments method, the
      predicted value was correlated with upper lobectomy but was overestimated in case
      of lower lobectomy. Meanwhile, in the VC analysis using CT method, the predicted
      value was correlated with RL or LU but was overestimated in case of RU or LL.
      This may due to the fact that RL and LU had large lobar volumes. In conclusion,
      postoperative predicted and actually measured values were different associated
      with resected lobe. In the FEV1.0 and VC analysis using subsegments method, the
      predicted value was strongly correlated with upper lobectomy but was
      overestimated (10%) in case of lower lobectomy.

PMID- 15957416
TI  - [Traumatic rupture of the ascending aorta].
AB  - A 42-year-old male was diagnosed as having a traumatic rupture of the ascending
      aorta 24 hours after traffic accident. On admission, the patient was in a state
      of shock, but he was successfully treated by emergency surgery. Traumatic rupture
      of the ascending aorta is a serious condition and the mortality may be very high.
      Although physicians rarely encounter patients with this condition, it is
      relatively common among autopsy cases with multiple trauma. Urgent diagnosis and
      treatment are mandatory.

PMID- 15957417
TI  - [Surgical treatment of lung cancer in octagenarian patient].
AB  - Because average life span of Japanese is getting longer, we sometimes meet elder
      lung cancer patients of over 80. They often have many complications, so we are
      worried about how to treat them. Recently we met 8 elder patients with lung
      cancer, and we performed surgical operation for them. Six patients performed
      partial lung resection or lobectomy had no complications after operation. But 2
      patients with respiratory disorder who performed lobectomy and chest wall
      resection had some complications after operation. In such patients, careful
      postoperative management is needed, and continuous positive airway pressure
      (CPAP) ventilation with pressure support (PS) may be useful to prevent
      respiratory complications.

PMID- 15957418
TI  - [Primary lung cancer; assessment of the disclosed 5-year survival rate by the
      Internet website].
AB  - The disclosed 5-year survival rate for lung cancer in the Internet website
      represents a various difference by each institution. The better inferiority of
      the survival has been listed in a table to compare with other institutions and
      has been reported in magazines and media with a lack of an enough inspection,
      i.e., with a sufficient considering of a risk adjustment such as patient's
      background, operative policy, postoperative adjuvant therapy, and statistical
      background. We report our outcome of the surgical treatment for primary lung
      cancer. Of 875 patients treated for lung cancer in our department for 23 years
      between January 1980 and December 2002, 115 patients containing of 42 cases in
      1997 and of 48 ones in 1992 and of 25 ones in 1987 were selected and the
      accumulated survival analysis was treated by Kaplan-Meier method. Eighty males
      and 35 females were between 15 and 80-year-old (average 63.2 +/- 11.4). The
      pathological classification was adenocarcinoma (n=69), squamous cell carcinoma
      (n=32), and others (n=14). The operative procedures were pneumonectomy (n=14),
      bilobectomy (n=12), lobectomy (n=85), and wedge resection (n=4). The survival
      time was from 29 days to 182 months (median survival time was 1471+/- 1180 days,
      the averaged time was 49 months). The 5-year survival rate was 41.4 +/- 9.1%
      (n=25) in 1987, 35.6 +/- 6.2% (n=48) in 1992, and 56.0 +/- 7.0% (n=42) in 1987,
      respectively (log-rank test, p = 0.2555). The 10-year survival rate was 24.1 +/-
      7.9% in 1987 and 8.5 +/- 3.6% in 1992, respectively. The 5-year survival rate was
      as follows: IA 81.0 +/- 8.6% (n=20), IB 73.7 +/- 10.1% (n=19), IIA 57.1 +/- 18.7%
      (n=7), IIB 55.6 +/- 16.6% (n=9), IIIA 28.6 +/- 7.6% (n=35), IIIB 15.4 +/- 10.0%
      (n=13), IV 16.7 +/- 10.8% (n=12), respectively. The 5-year survival rate was as
      follows: male 42.8 +/- 5.3% (n=80), female 63.2 +/- 7.3% (n=35), respectively (p
      = 0.0147). In regard to the histological classification, the 5-year survival rate
      was as follows: adenocarcinoma 47.2 +/- 5.9% (n=69), squamous cell carcinoma 50.8
      +/- 8.9% (n=32), respectively (p = 0.9012). As a rule of the disclosure on the
      internet website, we report our survival data by accompanying with minimum
      parameters such as, patient's background, pathological types, gender,
      pathological stages, and mean survival rate with standard error. When we compare
      the 5-year survival rate with other institutes, in considering of a risk
      adjustment, we would carefully have to estimate the determined survival rate with
      a standard error.

PMID- 15957419
TI  - [Left atrial sarcoma with the initial diagnosis of myxoma].
AB  - Primary tumors of the heart are rare. The majority of these tumors are benign,
      with myxomas located in the left atrium being the most common form. Almost all
      malignant tumors are sarcomas and occur preferentially in the right side of the
      heart. The case of a 73-year-old woman who presented with symptoms of mitral
      valve stenosis is reported. Echocardiography revealed a left atrial mass that was
      interpreted as atrial myxoma. At the operation, the tumor which was lobulated and
      had a smooth surface was arising from posterior wall of left atrium extending
      into the mitral annulus. Wide surgical excision was possible with left atrial
      reconstruction and mitral valve replacement. Histological and immunohistochemical
      studies revealed malignant undifferentiated sarcoma extending to the surface of
      mitral valve. Postoperative metastatic work-up showed no evidence of
      dissemination. The patient survived the operation without adjuvant radiation and
      chemotherapy and has been symptom-free over 1 year. At present, 16 months
      following the operation, the patient is alive with no evidence of disease.

PMID- 15957420
TI  - [Comparison of postoperative lung function between segmentectomy and lobectomy in
      patients with lung carcinoma].
AB  - BACKGROUND: To determine any potential advantages of segmentectomy, we compared
      preoperative and postoperative lung function of patients who underwent
      segmentectomy with those in patients who underwent lobectomy. PATIENTS & METHODS:
      Between September 2001 and November 2003, preoperative and postoperative lung
      function, including DLco, was assessed in 43 patients with primary lung
      carcinoma. Of these 43 patients, 33 underwent single lobectomy (group L) and 10
      underwent segmentectomy (group S). Both groups were examined for differences in
      lung volume through VC and FEV1.0 data, and all postoperative examinations were
      performed at 2 weeks after surgery. Changes in DLco (deltaDLco), VC (deltaVC) and
      FEV1.0 (deltaFEV1.0) were calculated and we compared the data for group L with
      those of group S. RESULTS: Mean values for deltaVC, deltaFEV1.0 and deltaDLco in
      group L were 31.8 +/- 9.3, 29.6 +/- 10.9 and 27.2 +/- 14.0%, respectively, while
      these values in group S were 22.9 +/- 7.9, 20.1 +/- 9.6 and 13.9 +/- 11.6%,
      respectively. deltaVC, deltaFEV1.0 and deltaDLco were significantly smaller in
      group S than in group L (p < 0.01, p < 0.05 and p < 0.05, respectively).
      CONCLUSION: Segmentectomy was superior to lobectomy with regard to preservation
      of lung function in the early postoperative period.

PMID- 15957421
TI  - [Off-pump coronary artery bypass grafting using graft to coronary shunt for acute
      coronary syndrome].
AB  - We developed graft to coronary shunt during off-pump anastomosis. Proximal
      anastomosis of saphenous vein graft (SVG) was done formerly, and vinyl chloride
      tube, 5 cm long and 2 mm in diameter, was inserted into SVG. Another end was
      inserted into coronary artery, and continuous suture around the tube was
      performed before removing the tube. This technique is fit to use for the
      anastomosis between SVG and #3. Because the tube is easily inserted into those
      parts without injury of intima, and distal right coronary artery needs enough
      blood supply. After the revascularization of left anterior descending artery and
      #3, the heart can be displaced to expose circumflex artery. We adopted this
      technique to 3 patients with acute coronary syndrome (ACS). Though this technique
      is not adopted for the patients having stenosis on #4, we conclude that SVG to
      coronary shunt could be a important part of the strategies of off-pump coronary
      artery bypass grafting (OPCAB) for ACS patients.

PMID- 15957422
TI  - [Acute penetrating neck trauma presenting with laryngotracheal injury].
AB  - Laryngotracheal injuries are serious complications in the case of penatrating
      neck trauma which may not commonly in Japan. In the last several decades, many
      authors have discussed method for accurate evaluation and immediate airway
      management for patient with laryngotracheal injury. But, standardization of the
      treatment is still controversial about mandatory exploration or selective
      exploration. We report 4 cases with fresh laryngotracheal injury due to
      penetrating neck trauma including 3 suicide attempt patients. In these cases,
      laryngotracheoplasty used by absorbable material was performed within 8 hours
      after trauma. Two cases of suicide attempt patients underwent tracheostomy at the
      lower level of the laryngotracheal injury. After these treatment, fiberoptic
      bronchoscopy was performed to evaluate the airway for 3 cases except 1 who was
      dead because of hemorrhagic shock on arrival. In 2 cases, the suture filament
      existed in the lumen of the larynx and trachea, there were no major granulation
      in the site of repairment and no infection. Three cases were extubated
      successfully and discharged without major airway problem. Two cases have
      psychiatric disease such as depression, so we must consider their psychiatric
      background in the future. In conclusion, penetrating laryngotracheal trauma, we
      should consider that serious airway injury may be hidden under the superficial
      small wounds. Also, rapid local wound exploration and laryngotracheoplasty is
      important for life-saving, and fiberoptic bronchoscopy is effective to prevent
      early respiratory complications and has value in the evaluation.

PMID- 15957423
TI  - [Left coronary ostial stenosis caused by syphilitic aortitis].
AB  - We report 2 cases of cardiovascular disease related to end-stage syphilitic
      infection, which is now relatively rare. A 49-year-old man (case 1), and a 45
      year-old man (case 2) were admitted to our hospital for angina pectoris. Cardiac
      catheterization showed severe aortic regurgitation and left coronary ostial
      stenosis. Active syphilis was detected in both cases by routine blood examination
      on admission. Oral ampicillin was started immediately to treat the syphilis;
      however, during the course of treatment, acute heart failure developed in both
      patients. We performed emergency aortic valve replacement and coronary artery
      bypass grafting. Intraoperatively, the orifice of the left coronary artery was
      almost occluded, and retrograde perfusion of cardioplegia was needed to induce
      cardiac arrest. Both patients recovered uneventfully. When treating patients with
      antibiotics for syphilitic disease, it is important to prepare for the
      possibility of urgent surgery.

PMID- 15957424
TI  - [Surgery for a pericardial diverticulum; report of a case].
AB  - We report a case with pericardial diverticulum in the mediastinum. A 64-year-old
      woman visited our hospital because of cough and dyspnea. Chest X-ray showed a
      smooth-bordered mass in the right superior mediastinum and computed tomography
      (CT) showed a homogeneous cystic mass in the paratracheal area. During right mini
      thoracotomy, a thin-walled cystic lesion was found involving the trachea, the
      superior vena cava, and the azygos vein. The cyst extended a duct toward the
      pericardium. We performed total excision and pathological examination confirmed
      the diagnosis of a pericardial diverticulum. Mini-thoracotomy provides an
      effective and minimally invasive means of excising the mediastinal mass,
      relieving symptoms, and allowing pathological examination.

PMID- 15957425
TI  - [Extraanatomical bypass grafting for a coarctation of the aorta in the adult:
      report of a case].
AB  - A 49-year-old man with a successful bypass grafting for coarctation of the aorta
      is presented. He has been suffering from hypertension since his 30s. Angiography
      and magnetic resonance imaging (MRI) revealed the stenosis of distal aortic arch
      and developed collateral circulation. After left thoracotomy, bypass grafting
      using a 16 mm woven Dacron graft was placed between the left subclavian artery
      and the descending aorta. He had a satisfactory postoperative course with no
      residual pressure gradient. We recommend this procedure to be a safe and
      minimally invasive technique that can avoid injury to the collateral.

PMID- 15957426
TI  - [Tetraplegia and respiratory failure due to carcinomatous neuropathy in the early
      postoperative period of a lung cancer patient: report of a case].
AB  - A 63-year-old man, with atypical pulmonary mycobacteriosis and also with hepatic
      dysfunction due to chronic hepatitis C, underwent wedge resection of the right
      lower lobe for non-small cell lung cancer. On the 9th postoperative day, the
      patient developed acute tetraplegia and then respiratory failure. Neither
      computed tomography (CT) nor magnetic resonance imaging (MRI) of brain and
      cervical vertebrae showed any cancer metastases. The neurological symptoms were
      those of Guillain-Barre syndrome. Therefore, we speculate that the cause of the
      neuromyopathy might be autoimmune antibodies from lung cancer. Steroid pulse
      therapy and plasma exchange treatment were effective and the patient's symptoms
      disappeared in a month. We reported the extremely rare case of a lung cancer
      patient with acute tetraplegia in the early postoperative period.

PMID- 15957427
TI  - [Metastatic carcinoma of the adrenal gland from large cell neuroendocrine
      carcinoma; report of a case].
AB  - A 69-year-old man had undertaken left upper lobectomy (ND 2 a) with partial
      resection of the left lower lobe under the diagnosis of a primary lung cancer,
      T2N0M0, stage IB in June, 2002. The histopathological diagnosis was large cell
      neuroendocrine carcinoma (LCNEC), T3N0M0, stage IIB. The patient was discharged
      on postoperative day 25. Abdominal computed tomography (CT) revealed an enhanced
      tumor in the left adrenal lesion, 3 cm in diameter, in October, 2003. Magnetic
      resonance imaging (MRI) showed a slightly low intensity mass on T1-weighted
      imaging and slightly high intensity on T2-weighted imaging without invasion to
      other organs. Tumor marker, NSE was slightly elevated on blood examination. Left
      adrenalectomy was performed with a surgical margin. Histopathologically, the
      tumor was diagnosed as metastasis of LCNEC. There is no evidence of recurrence
      for a year after surgery. Although a prognosis of LCNEC is poor in general, we
      should consider the resection of metastatic carcinoma of the adrenal gland from
      LCNEC for long-term survival expectantly.

PMID- 15957428
TI  - [The last period of surgical site infection after pulmonary resection for lung
      cancer with hemodialysis; report of a case].
AB  - An 80-year-old man had been on maintenance hemodialysis for nondiabetic chronic
      renal failure from June 1996. He underwent investigation of an abnormal chest X
      ray and was referred to our hospital with a diagnosis of squamous cell carcinoma
      in the upper lobe of the right lung. On February 20, 2003, right upper lobectomy
      was performed. The postoperative course was uneventful and he was discharged on
      postoperative day 13. Two weeks later he was readmitted with a wound infection.
      Although he received antibiotics, drainage, and wound lavage, his fever persisted
      and chest X-ray showed inflammatory changes in the right lower lung field. He was
      placed on mechanical ventilation for dyspnea. After this, his respiratory
      function became stable and he could be weaned from the ventilator within 2 weeks.
      The subsequent course was uneventful and he was discharged 1 month after re
      admission. This patient needed ventilation due to weakness caused by wound
      infection. Such infection is uncommon but can be fatal for a compromised host, so
      we administered antibiotics for 3 days until the wound closed.

PMID- 15957429
TI  - [Usefulness of the eradication of Helicobacter pylori for the patient with
      idiopathic thrombocytopenic purpura and lung cancer: report of a case].
AB  - A 61-year-old female was admitted because of an abnormal lung shadow on chest X
      ray. She had suffered from idiopathic thrombocytopenic purpura (ITP) for more
      than 7 years. Computed tomography (CT) revealed that an irregular shadow, about 2
      cm in diameter, was located in the upper lobe of the right lung. After
      intravenous immunogrobulin injections for 5 days, a hematology test indicated
      increased platelet counts and we performed thoracoscopic surgery successfully
      without blood transfusions. However, 4 months after surgery, a hematology test
      indicated decreased platelet counts again. Thirteen months after the operation,
      gastrointestinal fiberscopic examination showed Helicobacter pylori infection.
      After the urea breath test, eradication therapy let to a recovery in platelet
      counts.

PMID- 15957430
TI  - [Primary pulmonary meningioma; report of a case].
AB  - Primary pulmonary meningiomas are quite rare, and their occurrence has been
      reported only sporadically. A 49-year-old, asymptomatic female was hospitalized
      for the evaluation of a coin lesion in the left lung radiography. She has no
      history of previous neoplasm or symptom referable to the central nervous system.
      Chest computed tomography (CT) demonstrated a 9 x 14 mm, round, noncalcified,
      well-demarcated lesion in the left upper lobe of the lung (S(1+2)). For
      diagnostic purposes, enucleation of the tumor was performed. The resected
      specimen revealed histologically classical typical meningioma. Because
      postoperative magnetic resonance imaging (MRI) of the brain did not show any
      intracranial mass, this case was and diagnosed as a primary pulmonary meningioma.
      The patient was discharged with no complication, and alive without recurrence of
      disease 14 months after surgery.

PMID- 15957431
TI  - Gordon Memorial Lecture. Poultry mycoplasmas: sophisticated pathogens in simple
      guise.
AB  - Mycoplasmas are a genus within the class Mollicutes (trivial name mollicutes),
      which are the smallest known prokaryotes capable of self-replication. They have a
      very small genome, and have evolved to this 'minimalist' status by losing non
      essential genes, including those involved in cell wall synthesis. The mollicutes
      exploit their limited genetic material to the maximum and many are successful
      pathogens in man, animals, birds and plants. Most of those of veterinary
      importance are in the genus Mycoplasma and include 4 poultry pathogens of
      economic importance: Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma
      meleagridis and Mycoplasma iowae. The pathogenetic mechanisms of mycoplasmas are
      not fully understood, but they are successful pathogens because they can enter
      the host and multiply, evade the defence mechanisms, cause damage and escape to
      infect new hosts. M. gallisepticum is one of several motile species and possesses
      a terminal tip structure that mediates adherence to its target tissues. For some
      species, including M. gallisepticum, some of the organisms may become
      intracellular. Some Mycoplasma species, including the pathogenic poultry species,
      have a remarkable ability to vary their major surface antigens, a mechanism that
      is thought to help them to persist in their host by evading the immune response.
      The molecular and cellular events that lead to the development of lesions and
      clinical disease are still obscure. Some lesions appear to be the result of
      indirect damage from the host's inflammatory and cellular responses. Despite
      short survival times in the environment, mycoplasmas are able to transmit
      successfully to new hosts. In poultry flocks there is both horizontal and
      vertical transmission, the former being encouraged by intensive husbandry and
      stress factors. Establishing the pathways of transmission and the possible role
      of other birds, such as game and wild birds, as intermediate vectors between
      poultry flocks is now greatly aided by the availability of modern molecular
      methods for strain typing.

PMID- 15957432
TI  - Antipyretic effect of oral sodium salicylate after an intravenous E. coli LPS
      injection in broiler chickens.
AB  - A study was set up to investigate the influence of sodium salicylate on fever and
      acute phase reaction after lipopolysaccharide (LPS) injection in broiler
      chickens. An acute phase reaction was provoked through the intravenous injection
      of Escherichia coli LPS. Four oral doses of sodium salicylate were tested. Apart
      from body temperature, other inflammation indices, such as plasma corticosterone
      and ceruloplasmin, serum thromboxane B2 and zinc concentrations were monitored.
      Intravenous LPS induced a fever of about 1 degree C. A dose-dependent attenuation
      of the fever response of the chickens in the salicylate treated groups was
      observed. LPS-injected chickens also showed elevated plasma corticosterone and
      ceruloplasmin, while serum thromboxane and zinc concentrations decreased. Except
      for thromboxane B2, no linear relationship with increasing salicylate dose could
      be shown for the other blood variables. These data confirm that sodium salicylate
      is an effective antipyretic agent after injection of LPS in chickens, if used at
      an appropriate dosage. No dose-related change could be found for the other
      inflammation indices.

PMID- 15957433
TI  - Sodium salicylate attenuates lipopolysaccharide (LPS)-induced adipsia, but not
      hypophagia, in broiler chickens.
AB  - A study was conducted to determine the influence of sodium salicylate on the
      behaviour and the food and water consumption of broiler chickens after
      lipopolysaccharide (LPS) injection. An oral dose of 100 mg/kg sodium salicylate
      was given and an acute phase reaction in broiler chickens was provoked through
      the intravenous injection of Escherichia coli LPS. Water intake was higher in the
      LPS and salicylate-treated group than in the positive control group. The
      salicylate treatment, however, did not restore the food intake, or influence the
      behaviour of the chickens. These data show that sodium salicylate has a positive
      effect on the water intake after intravenous injection of LPS in chickens and
      suggests that there is a difference in mechanism of action of food and water
      consumption after LPS injection in chickens.

PMID- 15957434
TI  - Bacterial eggshell contamination in conventional cages, furnished cages and
      aviary housing systems for laying hens.
AB  - The influence of housing system on the initial bacterial contamination of the
      eggshell was studied. Two long-term experiments were performed. Bacterial
      eggshell contamination, as expressed by total count of aerobic and Gram-negative
      bacteria, was periodically analysed for eggs from a conventional cage, a
      furnished cage with nest boxes containing artificial turf or grids as nest-floor
      material and an aviary housing system. Results were log-transformed prior to
      statistical analyses. For both experiments no systematic differences were found
      between the conventional cage and furnished cage. The type of nest-floor material
      in the nest boxes of the furnished cages also did not systematically influence
      the bacterial contamination. A possible seasonal influence on contamination with
      a decrease in the winter period (up to > 0.5 log cfu/eggshell) of total count of
      aerobic and Gram-negative bacteria was observed in the first experiment. The
      contamination with total aerobic flora was higher (more than 1.0 log) on eggs
      from the aviary housing system compared to the conventional and the furnished
      cage systems. For Gram-negative bacteria this was not the case. During the entire
      period of both experiments, independent of housing system, shell contamination
      was not influenced by age of hens or period since placing the birds in the
      houses. For the total count of aerobic bacteria a restricted positive correlation
      (r2 = 0.66) was found between the concentration of total bacteria in the air of
      the poultry houses and initial shell contamination.

PMID- 15957435
TI  - Social interactions in Red Junglefowl (Gallus gallus) and White Leghorn layers in
      stable groups and after re-grouping.
AB  - Although social behaviour is a major factor affecting the coping of poultry in
      production environments little is known about how it has been affected by
      intensive selection processes in fowl. We attempted to clarify selection effects
      on overall repertoire and occurrence of different social behaviours as well as on
      aggressive responses to re-grouping with unfamiliar birds by comparing high
      producing White Leghorn layers to wild type Red Junglefowl. In the first
      experiment we observed 8 stable mixed sex groups/breed each consisting of four 24
      week-old birds previously familiar to each other. During 9 consecutive days, a
      wide range of social signals, sexual and aggressive interactions as well as
      spacing behaviour and activity were recorded over a 12-h photoperiod. In the
      second experiment, starting at 19 weeks of age, 16 single sex groups of three
      birds from each breed were formed by mixing unfamiliar individuals. Aggressive
      behaviours were recorded 0, 5, 24 and 48 h after re-grouping. Results from the
      stable groups indicated that the repertoire of social behaviours has been
      preserved during selection with few changes in frequencies and intensities.
      However, Leghorns showed a more cohesive spacing pattern than junglefowl. In the
      second experiment, aggressive activity was higher immediately and after 24 h
      following re-grouping in Leghorns, but there was a drop in the aggressiveness at
      5 h to the same level as junglefowl. We suggest that this may indicate poorer
      social learning capacity with a weaker ability to cope with group disruptions
      compared to the ancestral breed.

PMID- 15957436
TI  - Genetics of immunocompetent traits in a synthetic broiler dam line.
AB  - Three hundred and three chicks of both sexes, from a synthetic dam line (SDL) of
      broiler chickens, were studied for economic traits (body weights at 4, 5 and 6
      weeks of age) and immunological traits (humoral and cell mediated immune
      responses, and serum lysozyme concentration). The objective was to evaluate these
      traits and to estimate their genetic and non-genetic parameters. The humoral
      immune response was assessed by estimating the antibody response to sheep red
      blood cells using the haemagglutination (HA) test and serum IgG concentration
      using single radial immunodiffusion (SRID). The cell mediated immune (CMI)
      response was estimated as in vivo response to a mitogen (PHA-P). Serum lysozyme
      was measured by lysoplate assay. Least squares means for body weight at 4, 5 and
      6 weeks were 684 +/- 20, 920 +/- 19 and 1205 +/- 28 g, HA titre was 6.289 +/-
      0.246, CMI was 0.438 +/- 0.015 mm, lysozyme was 1.860 +/- 0.047 microg/ml and IgG
      was 6.287 +/- 0.194 mg/ml. There was an effect of sire on HA titre and on body
      weight at 4, 5 and 6 weeks of age; males were heavier than females. Heritability
      estimates were high for body weights but low for immunological traits. Phenotypic
      correlations (rp) among body weights were high and positive but were very low
      between body weights and most immunological traits. Among the immunological
      traits all rp were very low. Genetic correlations (rg) of body weights were
      positive and medium to high with CMI and HA and negative with serum IgG.

PMID- 15957437
TI  - Effect of daidzein on egg-laying performance in Shaoxing duck breeders during
      different stages of the egg production cycle.
AB  - The effect of a phyto-oestrogen, daidzein, on the laying performance of Shaoxing
      female ducks was examined in three experiments performed at different stages of
      the egg production cycle. Egg-laying rate, egg weight, egg composition, feed
      conversion ratio, hatchability characteristics of eggs and body weight, ovary and
      oviduct weight, as well as changes in serum concentrations of T3, T4 and E2 were
      recorded as response criteria. In the first experiment, 68 young ducks, 100 d of
      age, were given a basal diet (maize-soybean meal) with or without 3 mg of
      daidzein/kg diet for 42 d. Daidzein did not affect the onset of lay but
      apparently decreased egg-laying rate and mean egg weight as well as the feed
      conversion ratio. In the second experiment, 240 breeding ducks, 402 d of age,
      were allotted at random to three groups and given the basal diet containing
      daidzein at 0 (control), 3 (Da1) and 5mg/kg (Da2) for 35d. Egg-laying rate, mean
      egg weight and feed conversion ratio increased in both Da1 and Da2 groups.
      However, an adverse effect of daidzein on fertility and hatchability was
      observed. In the third experiment, 320 breeding ducks, 415 d of age, were fed on
      the basal diet with or without 5mg of daidzein/kg diet for 63 d. Egg-laying rate
      increased by 7.7%, average egg weight tended to increase, whereas yolk/albumen
      ratio decreased. Daidzein-treated ducks had higher body weight and oviduct weight
      compared with their controls. Elevated plasma T4 and E2 concentrations
      accompanied these phenotypic changes, but serum T3 was not affected. It is
      suggested that daidzein exerts divergent effects on the egg-laying performance of
      Shaoxing ducks under different physiological conditions and this action is dose
      dependent. The changes in circulating E2 imply possible participation of
      endogenous oestrogen in the mechanism of daidzein action.

PMID- 15957438
TI  - Effect of environmental enrichment during the rearing phase on subsequent
      eggshell quality in broiler breeders.
AB  - This study set out to investigate if access to an enriched environment during the
      rearing phase influences subsequent production and eggshell quality in broiler
      breeders. Broiler breeder pullets were reared under standard rearing conditions
      (control treatment) or under standard conditions with an environmental enrichment
      of bales of plastic-wrapped wood shavings (enriched treatment). At 19 weeks of
      age both groups were transported to a laying facility and housed in standard pens
      according to treatment type. Egg weight, shape, shell thickness, non-destructive
      deformation, breaking strength, stiffness and ultrastructural quality were
      compared at beginning of lay (25 weeks old), peak production (31 weeks old), mid
      lay (45 weeks old) and end of lay (57 weeks old). Production and hatchery data
      were also collected throughout lay. Significant treatment-age interactions were
      detected for non-destructive deformation, breaking strength and stiffness, such
      that birds which had received prior enrichment went on to maintain a better shell
      quality with age. The measurements of total shell thickness, mammillary thickness
      and effective shell thickness all showed a trend for a treatment-age interaction.
      Significant age effects were found for weight, shape index, shell thickness,
      breaking strength and stiffness. All production and hatchery data also
      demonstrated significant changes with age. It is concluded that early enrichment
      with bales of wood shavings may provide a novel approach to the maintenance of
      eggshell quality at a time when calcium metabolism begins to reduce in
      efficiency.

PMID- 15957439
TI  - Effect of intensity of eggshell pigment and illuminated incubation on
      hatchability of brown eggs.
AB  - The effects of intensity of brown eggshell pigment (light (LBP), medium (MBP) and
      dark (DBP)) and light intensity during incubation (low and high, 900 to 1380 and
      1430 to 2080 lux, respectively) on eggshell characteristics, embryonic growth,
      hatchability traits, chick hatching weight and hatching time were investigated
      using eggs from a meat-type breeder (Hybro) flock at 32, 36 and 41 weeks of age
      in three trials. With eggs of similar weights the intensity of brown pigment was
      not associated with eggshell weight and thickness, and did not influence embryo
      weight and egg weight loss during incubation. The shade of brown pigment of eggs
      laid by young hens influenced the percentage hatchability (HP) of eggs incubated
      under light. Illuminated incubation improved HP of LBP eggs (compared with MBP
      and DBP eggs) from 32- and 36-week-old hens, but had no significant effect on HP
      of eggs from 41-week-old hens. Light intensity during incubation did not
      influence egg weight loss. High intensity of light during incubation reduced HP
      and increased early death percentage (EDP) in the LBP and MBP groups, and did not
      influence HP and EDP in the DBP group. Brown eggshell pigment and intensity of
      light during incubation did not influence hatching time. It is concluded that the
      shade of brown pigment, intensity of light during incubation and age of the
      breeder hens influenced the hatchability performance of embryos from brown eggs.
      Light during incubation improved the hatchability of embryos in light brown eggs
      laid by young hens and the shade of brown pigment of eggs laid by older hens did
      not influence hatchability under illuminated incubation. High intensity of light
      during incubation reduced hatchability of light and medium brown eggs, but not
      the dark brown eggs.

PMID- 15957440
TI  - Age-related changes in the distribution of lean, fat with skin and bones in duck
      carcases.
AB  - The experimental birds were Pekin ducks (352 males and 352 females) reared to the
      age of 13 weeks. They were fed standard diets ad libitum. Starting from the
      second week, 21 males and 21 females were slaughtered every 7 d. Their carcases
      were divided into the following elements: neck, wings, legs, breast and back,
      which were then dissected into lean, skin with fat and bones. The body weights of
      one-day-old ducklings were similar (circa 62 g), but at 5 weeks of age the males
      were heavier than the females, and at 13 weeks of age their body weights were
      3537 g and 2994 g, respectively. In 2-week-old ducks 55.77% of lean was located
      in the legs, 15.91% in the back part, 2.78% in the wings, 12.47% in the neck and
      only 13.12% in the breast. Considerable changes in the distribution of lean were
      noted in the ducks aged 7 weeks. Its percentage decreased in the legs (to 29.34%)
      and increased in the breast and wings (to 36.86% and 10.96%, respectively). Age
      related changes in the distribution of skin with fat were smaller. Its percentage
      increased in the wings, legs and back, and decreased in the neck and breast.
      Until the age of 7 weeks the percentage of bones was decreasing quickly in the
      legs and increasing in the neck and breast, compared with their total weight in
      the carcase.

PMID- 15957441
TI  - Risk factors associated with Salmonella enterica subsp. enterica contamination of
      chicken carcases in Senegal.
AB  - This study was to identify the risk factors for Salmonella spp. contamination of
      Senegalese chicken carcases during slaughtering. One hundred and twenty
      traditional slaughterhouses were studied from January 2000 to December 2002 in
      and around Dakar. A questionnaire was answered by the slaughterers, and samples
      of breast skin were taken to assess the Salmonella status of chicken carcases.
      Results showed that 43.3% of the batches were contaminated with Salmonella,
      indicating Salmonella Hadar and Salmonella Brancaster as the two main serovars.
      Salmonella contamination of the carcases after slaughtering was related to
      contamination of the live birds. Feed withdrawal before slaughtering and thorough
      cleaning and disinfection procedures decreased the risk of contamination. One
      individual worker for each slaughtering stage was also associated with a
      decreasing risk of contamination. Using scalding water for plucking the chicken
      carcases increased contamination risk. These results will help slaughters to
      produce safer products for local consumers.

PMID- 15957442
TI  - Constant photoperiods and eggshell quality in broiler breeder pullets.
AB  - Broiler breeder pullets were exposed to constant 10-, 11-, 12-, 13-, 14- or 16-h
      photoperiods from 3 d of age. Egg weight, eggshell weight and shell thickness
      index were determined at 52 weeks of age. Egg weight increased by 0.31 g, shell
      weight decreased by 30 mg and shell thickness index decreased by 0.57 mg/cm2 for
      each one-hour increase in photoperiod. Whilst the changes in egg weight and
      eggshell thickness index might be overstated because eggs were collected at the
      same chronological time, the effect of time of egg-laying within the day was
      minimal in comparison, and did not negate the conclusion that egg weight
      increases, and shell weight and thickness index decrease with lengthening
      photoperiods. The effect of photoperiod on eggshell quality was not due to
      differences in the rate of lay between treatments. Shell weight was unaffected by
      time of lay.

PMID- 15957443
TI  - Dietary fish and evening primrose oil with vitamin E effects on semen variables
      in cockerels.
AB  - Our aim was to determine the effect of n-3 (2%, wt/wt, fish oil rich diet) and n
      6 (2%, wt/wt, evening primrose oil rich diet) fatty acid dietary supplementation
      and their combination with two concentrations of vitamin E (40 vs 200 mg/kg) on
      semen variables and on fatty acid and vitamin E profiles of spermatozoa in
      broiler breeders at 32, 42 and 52 weeks of age. The inclusion of fish oil in the
      cockerel diets increased the docosahexaenoic acid proportion in the sperm
      phospholipid fraction, which was almost threefold higher compared to the other
      two groups irrespective of vitamin E supplementation. In contrast, an increase in
      the proportion of total n-6 polyunsaturates, mainly 22:4n-6, was observed in the
      evening primrose oil group compared to the control only when the dietary content
      of vitamin E was increased to 200 mg/kg. Sperm concentration was decreased in the
      fish and evening primrose oil groups if vitamin E was 40 mg/kg, but such an
      effect was prevented in the fish, not the evening primrose oil group, by
      increasing the vitamin E to 200 mg. The proportion of motile spermatozoa was
      improved by the increased supplementation of vitamin E in all oil treatments.

PMID- 15957444
TI  - Effects of food deprivation and particle size of ground wheat on digestibility of
      food components in broilers fed on a pelleted diet.
AB  - The first aim of the experiment was to study the effect of wheat (Triticum
      aestivum) particle size on the digestibility of starch in a pelleted diet given
      to broilers. The second aim was to study the consequences of food deprivation
      before the excreta collection period (from 21 to 24 d). Wheat from a strong
      hardness cultivar was incorporated at 546.1 g/kg in diets. The other main
      ingredients were soybean meal (353.5 g/kg) and rapeseed oil (55.0 g/kg). Diets
      were given as pellets. The experimental design was a 2 x 2 factorial design
      testing two particle sizes of wheat flour and two procedures of a balance
      experiment (with or without food deprivation). Birds given diet C (wheat coarse
      grinding before pelleting) had significantly greater gizzard weight than birds
      fed on diet F (wheat fine grinding before pelleting). Starch digestibility value
      was significantly increased when birds were fed on diet F. This effect was halved
      by food deprivation. No significant effect of grain particle size was observed
      for protein and lipid digestibility values. However, food deprivation decreased
      apparent protein digestibility, with an effect which was more pronounced for fine
      than for coarse grinding. AMEN of the diet was significantly improved by fine
      grinding of wheat and decreased by food deprivation. However, no significant
      differences in growth performance were induced by differences in wheat grinding.
      No significant effect of grinding was observed on the water excretion:feed intake
      ratio. No significant difference was observed for vent score between treatments.
      There was over-excretion of starch in the first hours of refeeding following food
      deprivation.

PMID- 15957445
TI  - The effect of feeding hemp seed meal to laying hens.
AB  - Seed of the hemp cultivar Unika-b was cold-pressed to obtain hemp seed meal (HSM)
      containing 307 g/kg crude protein and 164 g/kg ether extract (60 g/kg linoleic
      acid, 120 g/kg alpha-linolenic acid, 160 g/kg oleic acid, lesser amounts of
      palmitic, stearic, and gamma-linolenic acids). For 4 weeks, 102 43-week-old
      DeKalb Sigma hens were fed on isonitrogenous and isoenergetic diets containing 0,
      50, 100 or 200 g/kg HSM. Eggs were collected for fatty acid analysis during the
      fourth week of feeding these diets. No significant differences were found between
      feed treatments for egg production, feed consumption, feed efficiency, body
      weight change or egg quality. Increasing dietary inclusion of HSM produced eggs
      with lower concentrations of palmitic acid and higher concentrations of linoleic
      and alpha-linolenic acids.

PMID- 15957446
TI  - Influence of age on the apparent ileal amino acid digestibility of feed
      ingredients for broiler chickens.
AB  - The apparent ileal digestibility of amino acids in 8 feed ingredients was
      determined using 14-, 28- and 42-d-old male broiler chickens. The ingredients
      included three cereals (wheat, sorghum and maize), one cereal by-product (mill
      run), three oilseed meals (canola, cottonseed and soybean meals) and one animal
      protein meal (meat and bone meal). Dietary crude protein in the assay diets was
      supplied solely by the test ingredient. All diets contained 20 g/kg acid
      insoluble ash as an indigestible marker, and each diet was offered ad libitum in
      mash form to 5 replicate pens from 11 to 14 d, 25 to 28 d and 39 to 42 d post
      hatching. There were 12, 6 and 6 birds per pen for the 14, 28 and 42 d samplings,
      respectively. The results suggest that the age of broilers significantly
      influenced the apparent ileal digestibility of amino acids. The effects, however,
      varied among amino acids and ingredients. In wheat, the digestibility of most
      amino acids was higher in 14- than in 28- and 42-d-old broilers. In maize, the
      digestibility coefficients of amino acids were higher at 28 and 42 d than at 14
      d. The digestibility coefficients in maize and wheat at 28 and 42 d were similar.
      The digestibility of amino acids in sorghum at 42 d was higher than those at 28
      d, but similar to those at 14 d except for histidine, lysine, serine and glycine,
      which were significantly higher at 42 d. Digestibility of amino acids in sorghum
      was similar between 14 and 28 d except for isoleucine, leucine, phenylalanine,
      glutamic acid and alanine. The digestibility of amino acids in mill run at 42 d
      was significantly higher than those at 14 and 28 d. There were no differences in
      digestibility between 14 and 28 d. In general, the digestibility of amino acids
      in canola meal, soybean meal and, meat and bone meal was higher at 28 and 42 d
      compared to those at 14 d, and similar between 28 and 42 d of age. In cottonseed
      meal, age had no effect on the digestibility coefficient of amino acids, except
      for lysine and arginine, which increased with age. Analysis of the combined
      results for the 8 feed ingredients showed that, in general, the digestibility
      coefficients of amino acids increased with advancing age of broiler chickens.

PMID- 15957447
TI  - A comparison of the effects of feeding treatments and lighting on age at first
      egg and subsequent laying performance and carcase composition of broiler breeder
      hens.
AB  - The effects of the growth curve from 15 to 20 weeks, age at photostimulation and
      pattern of photostimulus on sexual maturity, egg production and egg weight were
      evaluated in two trials with broiler breeder females to 56 and 34 weeks of age
      (housed in litter pens and individually caged, respectively). Carcase composition
      and reproductive morphology of hens varying in laying efficiency were measured in
      the second trial. Trial 1: Four growth curves were applied from 15 to 20 weeks to
      pullets housed in litter pens. Birds were transferred from 8- to 10-h
      photoperiods at 20 or 24 weeks of age, followed by weekly increments of one hour
      to reach a 16-h final photoperiod. Lower-than-recommended body weights at 20
      weeks significantly delayed sexual maturity, reduced peak rate of lay, total eggs
      and mean egg weight. However, double-yolked egg production was lower, resulting
      in non-significant differences in settable egg numbers between body weight
      treatments. Birds reared to the heaviest body weight exhibited a significantly
      advanced sexual maturity, but total egg numbers, peak rate of lay and mean egg
      weight were not significantly affected. However, the laying of more double-yolked
      eggs resulted in a decrease in the number of settable eggs. Delaying
      photostimulation to 24 weeks significantly retarded sexual maturity, reduced
      total and settable egg numbers, and increased mean egg weight. A tendency for
      fewer double-yolked eggs was observed. Trial 2: At 19 weeks, birds were selected
      from the 4 body weight categories in Trial 1 and moved to individual cages in 8
      rooms. Five lighting programmes were applied. The pattern of photostimulation
      applied did not affect any of the production traits measured. At 34 weeks, 24
      birds were selected for the analysis of reproductive morphology, presence of
      internal or multiple ovulations, and carcase composition. Eight hens showing an
      early age at first egg and regular egg production records, 8 birds showing
      erratic laying performance and 8 non-layers were killed for this purpose. There
      were no differences in carcase composition or reproductive morphology between
      these groups. No internal ovulations or double or multiple ovarian hierarchies
      were observed. The results presented confirm that broiler breeders do not require
      a lighting stimulus in order to initiate ovarian activity and that, where no
      lighting stimulus is given, body weight or feeding level plays a critical role in
      stimulating the birds to attain sexual maturity. However, when a lighting
      stimulus is given, factors such as body weight and body composition become
      relatively less important in regulating the age at sexual maturity.

PMID- 15957448
TI  - The effect of feeding time on shell quality and oviposition time in broiler
      breeders.
AB  - Three experiments were performed to determine the effect of feeding time on shell
      quality and oviposition time in broiler breeders. Mean eggshell thickness was
      increased significantly by 3.5 microm (approximately 1%) per h delay in feeding
      time when hens were housed in individual cages. However, eggshell thickness was
      not significantly affected by feeding time when birds were housed on litter
      floors. Mean oviposition time was delayed relative to lights on by 5 min per h
      delay in feeding time. Egg weight was not significantly affected by feeding time,
      suggesting that differences in shell thickness and oviposition times were not due
      to increased oviducal transit times. Producers who wish to implement delayed
      feeding may have to turn lights on earlier than usual to compensate for delayed
      oviposition times.

PMID- 15957449
TI  - [Dimitrie Gerota. The history of the well done thing].

PMID- 15957450
TI  - [Diagnosis and treatment in anal fissure].

PMID- 15957451
TI  - [Therapy of malignant liver tumors using microwave and radiofrequency ablation].
AB  - The aim of our study was to evaluate the efficiency for thermo-ablation with
      microwave and radiofrequency on patients with malignant liver tumors. From
      January 2002 to January 2005, in our Center of General Surgery and Liver
      Transplantation in 53 patients 70 sessions of thermoablation were carried out.
      The mean age was 58 years (25-79 years). Sex ratio men: women was 1.8 (34:19).
      The diagnosis was hepatocarcinoma in 38 patients (72%), liver metastases from
      colorectal cancer in 9 (17%) and from non-colorectal cancer (6-11%). The most
      tumors were single (36-68%). The mean diameter was 39.5 mm (9-94 mm).
      Percutaneous approach was used in 14 interventions (20%), laparoscopic in 2 (3%)
      and open approach in 54 cases (77%). We performed 54 sessions of microwave
      ablation in 42 patients and 8 sessions of radiofrequency ablation in 5 patients.
      Both methods were applied in 6 patients during 8 sessions. Tumor ablation was
      done together with liver resection in 10 patients (19%) and resections of other
      organs in other 8 patients (15%). Morbidity was 12%. The encountered
      complications were ascites, right pleural effusion and liver abscesses. There was
      no death. Total and partial necrosis was observed in 27, respectively 20
      patients. Local recurrence occurred in one patient but distal liver recurrences
      were diagnosed in 13 patients. After thermoablation for partial necrosis, local
      or distal recurrences patients received arterial chemoembolization (5), systemic
      chemotherapy (23), liver resection (1) and transplantation (1). The mean survival
      at 1 year and 3 years was 77% and respectively 38%. Microwave or radiofrequency
      ablation is a simple treatment method, with proved efficiency and minimal risks
      whose main indication is unresectable tumor.

PMID- 15957452
TI  - [Intraabdominal malignant pathology missed at laparoscopic cholecystectomy].
AB  - Due to its overwhelming benefits, laparoscopic cholecystectomy represents the
      "gold standard" for the treatment of symptomatic gallbladder stones. Allowing us
      to quickly solve an easy to diagnose pathology (by ultrasonography), in some
      cases it may lead us to mis-diagnose some major intraabdominal pathology, perhaps
      by a superficial interpretation of our clinical examination and para-clinic
      investigation data. Studying the archives of our clinic from January 1995 up to
      December 2003, we found 15 cases of intraabdominal neoplasia diagnosed in the
      year that followed laparoscopic cholecystectomy: 7 colorectal cancers, 4
      pancreatic cancers, 2 gastric carcinomas, one uterine and one adrenocortical
      malignancies. Among these, 6 cases were in an advanced stage--because of local
      invasion or distant metastases--without the possibility of radical, curative
      surgery. Only 4 of the 15 cholecystectomies were performed for acute
      cholecystitis. The average age was 56.3 years, under the age when such
      malignancies have the maximum incidence.

PMID- 15957453
TI  - [Ambulatory treatment of anal fissure].
AB  - Not a long time ago, the standard treatment for anal fissure was surgical,
      inpatient care; this concept failed in the last years, ambulatory treatment
      becoming the rule and the inpatient care the exception. We wish to present here
      our results in 125 ambulatory patients, who were referred to our proctologic
      office with anal fissure. We used two methods: a conservative one, by applying
      topical 0.2% nitroglycerine, similar to other proctology practitioners, and one
      method of our own which is a minimal surgical procedure consisting of
      sphincterotomy. The average follow-up period was 6 months. Symptom-free and
      anatomic-free states were obtained in 61.2% for conservative treated patients and
      in 91.4% for operated patients, respectively. We had no postoperative
      complications, rebounds or sequelae. We consider the results at least equal in
      effectiveness to those of standard surgical treatment. This is why we underline
      that ambulatory treatment for anal fissure reaches the goal to be of a first line
      option.

PMID- 15957454
TI  - [Treatment of chronic anal fissure using closed internal and lateral
      sphincterotomy].
AB  - When the conservative treatment of the chronic anal fissure (nitrates, topical
      calcium channel blockers, topical nifedipine, lignocaine and cortisone compounds)
      proves to be inefficient, the surgery may be opted for. From among all surgical
      procedures (anal dilation, fissure excision, anal advancement flap) we have opted
      for closed internal and lateral sphincterotomy. During the period of 1990-2002,
      there have been performed by just one surgeon 47 sphincterotomies (15 men-32
      women), average age 49 (23-76). RESULTS: There has not been any case of anal
      incontinence for gases or faeces, precocious or late; 1 para anal hematoma
      (2.12%) solved through puncture; 2 anal abscesses (4.25%), solved through
      incision and tegmen drainage. Control in 6 month's time and 1 year time: normal
      quality of life, without any subjective complaints; painless rectal touch,
      healing of the fissure, extensible anal sphincter, normal continence. The
      sphincterotomy was followed by the disappearance of the cleft syndrome with all
      patients. Although the literature contains citations of transitory and minimum
      incontinence in 2-4% of the cases, we have not noticed in any; no recurrences
      have been registered; morbidity is acceptable. The future will decide if, between
      sphincterotomy and the injection with the botulinum toxin, the latter one is to
      be preferred.

PMID- 15957455
TI  - [The limits of surgery in the treatment of the icteric patients due to pancreatic
      head cancer].
AB  - Aim is to present the limits of surgery, determined by the dimension of the tumor
      and vascular invasion, in the treatment of the icteric patients with pancreatic
      head cancer. This paper is a retrospective study realized in Timisoara City
      Hospital, Surgery Clinic, on 68 patients, hospitalized for icteric syndrome due
      to pancreatic head cancer. Surgery was performed in 66 patients: 4 (6%)
      pancreaticoduodenectomy, Whipple modified technique, 62 (94%) palliative surgery
      which consists in a biliodigestive shunt associated with a gastroenterostomy, and
      2 patients were not operated. In palliative treatment, 10 (15%) patients had
      complications and 3 (4.5%) died within 1 month after surgery. In the case of the
      patients with duodenopancreatectomy, there was no morbidity or mortality.
      Survival after one year was 0% in palliative treatment and 100% in
      pancreaticoduodenectomy. In icteric patients due to pancreatic head cancer, the
      possibility of pancreaticoduodenectomy without vascular resection is reduced
      (6%). Modified Whipple technique was imposed by the dimensions of the tumor (more
      than 3 cm) and vascular invasion, determining in the first place, the dissection
      of the vascular tree: portal, mesenteric, caval; and pancreaticoduodenectomy was
      performed only if there was no invasion.

PMID- 15957456
TI  - [Reconstruction strategy in chest wall defect relating to the localization of the
      lost substances: retrospective study of 18 patients].
AB  - OBJECTIVE: To evaluate an original algorithm in function of the chest wall defect
      localization after large surgery for cancer including more than 3 ribs. PATIENTS
      AND METHODS: Our retrospective study on 18 patients (10 women, 8 men), operated
      by the senior author, showed 8 pathological tumor localization in the central
      chest region, 7 in the lateral region and 3 borderline localizations. For central
      localizations, when the sternum was resected, the reconstruction was realized
      with a Gore-tex mesh in depth, metal hooks (staples) and Marlex mesh under the
      musculocutaneous superficial coverage flap. Lateral localizations was done by a
      Gore-tex mesh covered by the musculocutaneous flap; the borderline localizations
      were covered by a Marlex mesh and superficial musculocutaneous flap. The
      superficial coverage flaps were performed by latissimus dorsi flaps in 16 cases
      and transversus rectus abdominis flap in 2 cases. RESULTS: All the patients were
      extubated and breathed spontaneously in the postoperative period. Two deaths and
      one infection were to regret at distance. No flap was lost. CONCLUSION: The
      algorithm of reconstruction according to the location of the defect allows a
      simplification of the indications.

PMID- 15957457
TI  - [Classical and laparoscopic therapeutic options in surgery for hepatic abscess].
AB  - Although lots of modern surgical and imaging techniques have been developed and
      last generation antibiotics are in use, the difficulties in the diagnosis and
      treatment of hepatic abscesses are still a rather sombre reality. Our research
      concerning 14 patients submitted to surgery within the last ten years can be
      thought of as a record, considering the poor number of cases in the last decades.
      So, our study also includes the possible clinical or imaging errors, the
      technical details of the surgery, the attitude towards the abscess cavity and the
      still obscure etiology in most of the cases. The correlation between the surgical
      risk and the rest of the hepatic volume, evaluated by computed scanning
      technique, represents another objective of this paper. In the large or in the
      multiple disseminated abscesses, the small area of the remaining functional
      hepatic tissue, was correlated to the postoperative slow or even bad evolution in
      two cases. The radiological, ultrasound and scanner control showing the reducing
      or disappearing of the abscess cavity after drainage in all the cases, represent
      an argument of the correct therapeutic approach.

PMID- 15957458
TI  - [Hepaticojejunostomy].

PMID- 15957459
TI  - [Pancreatic carcinoma with osteoclast-like giant cell tumor and portal vein
      fistula].
AB  - Osteoclast-like giant cell tumor of the pancreas (OGTP) is a rare neoplasm. We
      report a case of OGTP involving the head of the pancreas in a 64 year old woman
      with an uncommon complication--portal vein fistula. We present the diagnostic
      strategy and therapy. Postoperative outcome after Whipple's pancreatoduodenectomy
      was uneventful. The patient is still alive at 16 month after operation, without
      disease recurrence.

PMID- 15957460
TI  - [Sacrococcygeal teratoma in an adult female operated with abdominoperineal
      approach].
AB  - The authors present the case of a 28 years old female with a mature, three-layers
      sacrococcygeal teratoma, which has been operated using an abdominoperineal
      approach. Teratomas are quite frequent in pediatric surgery; their incidence
      gradually decreases in adult population. Lately, significant progresses in the
      diagnosis and treatment of fetus and new born teratomas have been achieved; a
      review of the literature (2000-2004) is added. In adults, the diagnosis of
      teratomas is rather difficult. The symptoms are due to their size, to the
      compression of pelvic viscera or to their complications (infections, bowel
      obstruction, fistulas, malignancy). The treatment of teratomas is mainly
      surgical. The approach depends on the peculiarities of each case (size, invasion
      of the nearby viscera).

PMID- 15957461
TI  - [Unusual late complication after esophagoplasty type Gavriliu II for esophageal
      stenosis from chemical burns--cancer of the esophagoplasty tube].
AB  - We present the case of a 56 year old female, who in 23 years after esophagoplasty
      type Gavriliu II, with pre-sternal tube for esophageal chemical burn stenosis,
      develops a cancer in the upper third of the gastric tube, with a fast evolution
      to malnutrition, through lumen obturation. The evolution post-esophagoplasty was
      marked by malfunction of the neo-esophagus, characterized through dysphagia and
      distal dilatation, requiring many abdominal and pre-sternal reinterventions. The
      objective of the present surgical intervention was to assure a way for enteral
      nutrition (gastrostomy for feeding) and to extirpate the gastro-esophagoplasty
      tube. It is discussed the characteristic feature of the case: the difficulty of
      the stage-evolutive integration of this malignant disease location, the
      etiopathogenic factors that contributed to the malignant evolution of the antral
      portion of the gastro-esophagoplasty tube, the limits of the surgical treatment.

PMID- 15957462
TI  - [Complex microsurgical reconstruction of diabetic foot].
AB  - Microsurgical techniques increased the operability of patients with critical limb
      ischemia to more than 95%. However, the percentage of ischemic limb salvage
      remains limited, especially in diabetic patients with associated tissue gangrene
      and neuropathy. The study presents a 67 years old female patient with type II
      diabetes mellitus and critical limb ischemia, complicated with progressive
      gangrene of the pre-calcaneal region and thus representing a classical indication
      for thigh amputation. A sequential femur-popliteal-tibial anterior by-pass was
      performed, followed by soft tissue reconstruction using a latissimus-dorsi
      musculo-cutaneous free flap. Two years postoperatively, the patient developed
      clinical signs of symmetrical peripheral distal neuropathy, managed by bilateral
      posterior tibial nerve decompression. The patient follow-up was of 3 years.
      Through the entire period, distal pulse (ram of posterior tibial artery) remained
      present with a good integration of the flap and with absent clinical and
      paraclinical signs of neuropathy. The patient regained full ambulation.
      Morphologically and functionally the affected limb is entirely salvaged. Using
      microsurgical techniques, a more complex and complete approach of the diabetic
      patient with ischemic-neuropathic syndrome can be considered. This includes
      revascularization, soft tissue reconstruction and nerve decompression. In
      selected patients with indication of major amputation these methods offer a
      salvage option, with excellent long-term results.

PMID- 15957463
TI  - [Laparoscopic cholecystectomy for porcelain gallbladder].
AB  - The porcelain gallbladder is uncommon type of chronically inflamed gallbladder
      wall considered to be associated with a high frequency of adenocarcinoma and
      subsequently not suitable for a laparoscopic approach. In 12,000 patients chosen
      for a laparoscopic cholecystectomy 4 porcelain gallbladders were diagnosed. In 2
      cases the laparoscopic approach was successful. One conversion was due to an
      unconfirmed suspicion of gallbladder cancer and the other one to a fistula
      between the gallbladder and the common bile duct. Patients with a preoperative
      diagnosis of porcelain gallbladder must not be excluded from the laparoscopic
      approach yet a low threshold for conversion must be maintained in those with a
      cancer suspicion.

PMID- 15957464
TI  - [Post-traumatic acute appendicitis in hernia's sac].
AB  - The paper presents two unusual pathological aspects of a hernia and an
      appendicitis. It is about a massive old inguinal hernia, with strangulation and
      an intra-saccular congestive acute appendicitis that occurred after a traumatic
      injury of the region. The presumptive diagnosis through a dynamic monitoring of
      the patient, clinical and biological analysis has made possible a favorable
      solution of the case.

PMID- 15957465
TI  - ["Ring" colostomy--technical artifice of over rod colostomy].
AB  - Out of the wish to immediately postoperatively apply the colostomy bags on a
      stoma, we invented a simple technical artifice allowing the colostomy opening and
      prosthetics in the operating room: the tube ends passed under the outside colon
      are united so that they form a ring above the loop that can be easily introduced
      in the colostomy bag.

PMID- 15957466
TI  - [Reflections about training demands in clinical allergists and immunologists and
      pediatricians who attended to the XII National Congress of Allergy and Pediatric
      Immunology, Leon, Guanajuato, Mexico, 2004].

PMID- 15957467
TI  - [The Global Initiative for Asthma and familial medicine-resident physicians.
      Impact of an educational strategy].
AB  - BACKGROUND: The Global Initiative for Asthma (GINA) provides effective medical
      care to asthmatic patients. Knowledge and appropriate handling of GINAS'
      management guidelines for medicine residents significantly reduce asthma
      morbidity and mortality. OBJECTIVE: To evaluate the level of knowledge about
      asthma on Global initiative for Asthma program before and after an educational
      strategy in residents. MATERIAL AND METHODS: Forty-four residents of first,
      second, and third grade of UMF No. 21 and No. 28 took part in this project A
      magisterial lecture and a workshop about clinical cases on asthma were carried
      out. The lecture lasted three hours and asthma surveys, before and after the
      educational strategy; were applied. Descriptive statistics as well as t test in
      SPSS were used for statistical analysis. RESULTS: Average grade of the 44
      residents before the workshop was of 4.24 +/- 1.6, and after the workshop of 6.00
      +/- 1.71. Therewere no significant differences among groups peryear of medical
      residency onthe initial assessment; however, residents of first year showed an
      increment on asthma knowledge (p < 0.05) in the subsequent test. There were no
      differences among groups. CONCLUSIONS: Asthma educational workshops increase
      residents' awareness of asthma, mainly first-year medical students.

PMID- 15957468
TI  - [Function of flow cytometry on the dosage of antibodies against double stranded
      DNA in systemic lupus erythematosus].
AB  - BACKGROUND: Among the diverse number of antibodies observed in systemic lupus
      erythematosus, antibodies against double stranded DNA (anti-dsDNA) represent
      important serologic markers for the disease diagnosis and the follow-up of the
      disease activity. OBJECTIVE: To evaluate the role of a new quantitative
      methodology to detect antibodies against double stranded DNA in systemic lupus
      erythematosus and its association with the disease activity. MATERIAL AND
      METHODS: The performance of the indirect immunofluorescence flow cytometry with
      Crithidia luciliae as substrate was compared with the Crithidia luciliae indirect
      immunofluorescence assay and the ELISA technique in order to detect antibodies
      against double stranded DNA in 54 sera from 47 patient with systemic lupus
      erythematosus and 100 sera from normal controls. RESULTS: The new method showed a
      sensitivity of 78% and a specificity of 81% when the Crithidia luciliae indirect
      immunofluorescence assay was the gold standard. Compared with the ELISA
      technique, the flow cytometry showed a sensitivity of 78% and a specificity of
      86%. No correlation was found among antibodies against double stranded DNA values
      detected with flow cytometry and the MEX-SLEDAI activity scores. However, the
      flow cytometry showed a sensitivity of 70% and a specificity of 42% to
      distinguish patients with systemic lupus erythematosus with and without activity
      (MEX-SLEDAI score > or = 5). The Rho intra-observer coefficient was 0.61 (p <
      0.0001). CONCLUSIONS: In spite of the fact that this new method might represent
      an interesting advance for antibodies against double stranded DNA quantitative
      testing, a clear superiority does not emerge when it was compared with more
      traditional assays. Difficulties related with its reproducibility might represent
      a limitation in the routine use of this new method.

PMID- 15957469
TI  - [Identification of the learning needs of asthmatic diseases in relatives of
      pediatric patients].
AB  - BACKGROUND: Information on asthma is fundamental for an adequate control and
      management of patients who suffer from it, or for their relatives; hence, new
      educational programs are being carried out in order to achieve this aim.
      OBJECTIVE: To identify learning requirements for its subsequent use in the
      development of an educational program. MATERIAL AND METHODS: A descriptive study
      was carried out. 326 surveys were applied to relatives of pediatric patients seen
      at the allergology department of Hospital Leonor Perez, from April to September
      2003. Frequencies, percentages, as well as Pearson's chi-square test were used in
      order to compare groups. RESULTS: An inadequate knowledge of treatment was
      observed in 69.3% of the cases, of its physiopathology in 84.7%, of its
      preventive medication and of crisis in 51.7 and 59.5%, respectively, as well as
      from the importance of both treatments in 65.3% of them. Most of the relatives
      included in this study recognized the importance of being instructed in the
      disease process (94.8%). There were no significant differences between the group
      of relatives with prior specialized attention and the group who attended
      consultation for the first time; except for preventive medication to treat
      crisis, where the first one showed better knowledge of the disease (p = 0.002).
      Difference on the overall knowledge was also better in the first group, although
      lower than expected. CONCLUSIONS: It is important to apply an educational program
      aimed at improving levels of knowledge on specific aspects of asthma.

PMID- 15957470
TI  - [Comparative meta-analysis of immunoestimulant agents used in pediatric patients
      in Mexico].
AB  - OBJECTIVES: To gather basic information of the double-blinded, placebo controlled
      studies about the use of immunostimulant agents to prevent acute respiratory
      infections in children and to make a meta-analysis of each one of them after six
      months of treatment. MATERIAL AND METHODS: Articles related to immunostimulant
      agents were looked up in Medline and EMBASE, and the ones referring to controlled
      studies were selected. Average data and the dispersion of the number of acute
      respiratory infections were extracted and combined as average differences
      considering the random-effect model for each one of the immunostimulant agents.
      RESULTS: Only D53, LW50020, OM-85, pidotimod, and RU41740 had controlled studies.
      It was only possible to calculate the combined effects of D53, OM-85, pidotimod,
      and RU41740. The effects in the reduction of the number of acute respiratory
      infections were: global D53 -0.92 (-1.46, -0.39), average difference (confidence
      interval 95%) (p < 0.05); global OM-85 -1.20 (-1.70, -0.69) (p < 0.05), OM-85 in
      Mexico City -1.55 (-2.00, -1.10) (p < 0.05); global pidotimod -0.82 (-1.84,
      +0.21) (p > 0.05); global RU41740 -0.81 (-2.24, +0.62) (p > 0.05), RU41740 in
      Mexico City -1.20 (-4.33, +1.94) (p > 0.05). Effects in the reduction of acute
      respiratory infections as percentages were: global D53 31.86% (-34.32, -29.40) (p
      < 0.05); global OM-85 -39.28% (-52.58, -25.98) (p < 0.05), OM-85 in Mexico City 
      46.85% (-54.98, -38.72) (p < 0.05); global pidotimod -31.26% (-42.51, -20.01) (p
      < 0.05); global RU41740 -27.60 (-73.88, +18.69) (p > 0.05), RU41740 in Mexico
      City -27.89 (-104.11, +48.33) (p > 0.05). DISCUSSION: Only D53 and OM-85 proved
      to have significant effect in the prevention of acute respiratory infections in
      children. Only OM-85 showed significant efficacy in Mexico City. LW50020,
      pidotimod, and RU41740 have some evidence of their efficacy, contrary to other
      immunostimulant agents that do not have it.

PMID- 15957471
TI  - [Treatment with high doses of intravenous immunoglobulin in a case of complicated
      pemphigus vulgaris].
AB  - A case of a young woman with recalcitrant pemphigus vulgaris involving skin and
      mucosae, with multiple side effects due to the chronic use of corticosteroids and
      azathioprine related myelosuppression is presented. She received high doses of
      intravenous immunoglobulin for five consecutive days and showed a rapid disease
      control, with healing in three weeks. Remission observed in this patient supports
      the idea that intravenous immunoglobulin is a good alternative of treatment for
      patients with pemphigus vulgaris, when there is no response to it or when
      significant adverse effects appear as a result of its prolonged use.

PMID- 15957472
TI  - [Expert' consensus in the current therapeutic use of intravenous immunoglobulin].

PMID- 15957473
TI  - [Up-to-date Mexican consensus in Allergic Rhinitis and its Impact on Asthma,
      2005. ARIA].

PMID- 15957474
TI  - Results of pars plana vitrectomy in closed-globe injuries.
AB  - BACKGROUND AND OBJECTIVE: To assess surgical and visual outcomes with pars plana
      vitrectomy (PPV) in closed-globe injuries resulting in anterior and posterior
      segment pathologies and evaluate the factors influencing the prognosis. PATIENTS
      AND METHODS: Retrospective observational study. Forty-seven eyes of 47
      consecutive patients who underwent PPV because of closed-globe injury between
      January 1992 and August 2003 were reviewed. Surgical and visual outcomes and
      prognostic factors were analyzed according to the Ocular Trauma Classification
      System. RESULTS: Preoperative visual acuity was less than 4/200 in 49% of eyes,
      classified as grades IV to V. After surgery, this ratio was 23% (P < .05). Final
      visual acuity was statistically significantly better in grade I (P = .0001),
      grade II (P = .002), and relative afferent pupillary defect-negative (P = .0001)
      injuries. Maculopathy was the most common adverse outcome influencing final
      visual acuity (32%), followed by secondary glaucoma (13%) and proliferative
      vitreoretinopathy (8%). CONCLUSION: PPV is a favorable treatment modality in
      severe closed-globe injuries. Assessment of injuries with respect to the Ocular
      Trauma Classification System seemed to predict visual outcomes in this series.

PMID- 15957475
TI  - Surgical management of non-metallic and non-magnetic metallic intraocular foreign
      bodies.
AB  - BACKGROUND AND OBJECTIVE: To identify clinical features and evaluate outcomes of
      vitreoretinal surgery in eyes with retained non-metallic and non-magnetic
      metallic intraocular foreign bodies (IOFBs). PATIENTS AND METHODS: Retrospective
      chart review. Thirty-two eyes (28 patients) with non-metallic and non-magnetic
      metallic IOFBs underwent removal of IOFBs with intraocular forceps, either via
      the pars plana in 30 eyes (93.9%) or a limbal approach in 2 eyes (6.25%). The
      main outcome measures were postoperative visual acuity, rate of retinal break
      formation, development of retinal detachment, and type of IOFB. RESULTS: IOFBs
      were non-metallic in 22 eyes (68.7%) and non-magnetic metallic in 10 eyes
      (31.1%). The average follow-up period was 7.5 months. Overall, final visual
      acuity was 20/40 or better in 10 eyes (31.1%) and 5/200 to 20/50 in 10 eyes
      (31.1%). A higher incidence of retinal break formation posterior to the
      sclerotomy was seen with glass IOFBs (P = .02). Retinal detachment was observed
      preoperatively in 4 eyes (12.5%) and postoperatively in 2 eyes (6.25%).
      CONCLUSION: Final visual outcome was independent of size and type of IOFB. Pars
      plana extractions may be associated with a higher rate of retinal break formation
      and subsequent retinal detachment, particularly with glass IOFBs.

PMID- 15957476
TI  - Unambiguous comparison of juvenile and senile rhegmatogenous retinal detachment.
AB  - BACKGROUND AND OBJECTIVE: To investigate whether age is a prognostic factor in
      rhegmatogenous retinal detachment (RRD). PATIENTS AND METHODS: The patient
      population was divided into two groups according to age at onset of RRD (juvenile
      R RD = younger than18 years and senile RRD = 65 years and older). The juvenile
      RRD group consisted of 35 patients and the senile RRD group consisted of 39
      patients. RESULTS: There were statistically higher incidences of male patients,
      trauma, subretinal fibrosis, and myopia in the juvenile RRD group compared
      withthe senile RRD group. In addition, there were statistical differences in the
      break characteristics, extent of RRD, and severity of proliferative
      vitreoretinopathy between the juvenile and senile RRD groups. However, no
      statistical differences were evident in the final retinal reattachment rate
      (88.6% vs 94.9%; P = .413) or the final visual outcome (P = .902) between
      juvenile RRD and senile RRD. CONCLUSION: Clinical characteristics between
      juvenile and senile RRD are different. Although delayed diagnosis is common, the
      final surgical outcome in juvenile RRD is as promising as in senile RRD.

PMID- 15957477
TI  - A cluster of patients with acute-onset endophthalmitis following cataract
      surgery.
AB  - BACKGROUND AND OBJECTIVE: To describe a cluster of patients who had acute-onset
      endophthalmitis following cataract surgery. PATIENTS AND METHODS: Ten patients
      with endophthalmitis following cataract surgery who were referred from three
      different anterior segment surgeons were evaluated. RESULTS: Presenting visual
      acuities ranged from 20/30 to light perception (median, 20/80). All 10 eyes
      demonstrated vitritis, 8 of 10 eyes had hypopyon, and the remaining 2 eyes had
      significant anterior segment fibrin. All patients were treated with intravitreal
      injections of vancomycin and ceftazidime, as well as subconjunctival steroids.
      Vitreous cultures were positive in 2 of 10 eyes, and both grew Staphylococcus
      epidermidis, aqueous cultures were negative in 8 of 8 eyes (not performed in 2
      patients). Follow-up ranged from 13 to 85 days (median, 37 days). All eyes showed
      complete resolution of inflammation and visual acuity improved to 20/40 or better
      in 9 eyes (90%). CONCLUSIONS: Acute-onset endophthalmitis may occur in a cluster
      of patients within a short time frame. Early diagnosis and treatment may result
      in favorable visual outcomes.

PMID- 15957478
TI  - Long-term results of pars plana vitrectomy combined with filtering surgery for
      neovascular glaucoma.
AB  - BACKGROUND AND OBJECTIVE: To analyze the effectiveness of vitrectomy combined
      with filtering surgery for neovascular glaucoma. PATIENTS AND METHODS: Twenty-one
      eyes with neovascular glaucoma underwent pars plana vitrectomy combined with
      filtering surgery between January 1995 and December 2003. Thirteen eyes (10
      cases) had neovascular glaucoma secondary to proliferative diabetic retinopathy
      and 8 eyes (8 cases) had neovascular glaucoma secondary to central retinal vein
      occlusion. The initial intraocular pressures ranged from 21 to 70 mm Hg with full
      medication. All cases were observed for more than 12 months after the last
      surgery and the ophthalmic records were retrospectively reviewed. RESULTS: During
      the follow-up period, 19 eyes (90.5%) had intraocular pressures of less than 21
      mm Hg with or without antiglaucoma eye drops, whereas 18 eyes (85.7%) had a
      stable or improved visual acuity. CONCLUSION: Vitrectomy combined with filtering
      surgery is considered to be an effective treatment for neovascular glaucoma to
      maintain the visual function for a long period.

PMID- 15957479
TI  - Clinical evaluation of refractive changes following brow suspension surgery in
      pediatric patients with congenital blepharoptosis.
AB  - BACKGROUND AND OBJECTIVE: To evaluate the postoperative visual acuity and
      refractive changes occurring after bilateral frontalis brow suspension surgery in
      pediatric patients with congenital blepharoptosis. PATIENTS AND METHODS: Twenty
      three patients between 4 and 12 years old with severe congenital blepharoptosis
      (unilateral in 21 cases and bilateral in 2 cases; total of 25 eyes) and poor
      levator function underwent bilateral frontalis brow suspension surgery by
      Crawford's double triangle method with 4:0 expanded polytetrafluoroethylene
      sutures. The non-ptotic eyes (21 eyes) undergoing frontalis brow suspension
      surgery served as the control group. All patients had best-corrected spectacle
      visual acuity (BCSVA) of more than 6/9 preoperatively in both eyes. Changes in
      the postoperative BCSVA, binocularity, relevant refractive parameters, lid
      position, lagophthalmos, lid lag, and tear break-up time were evaluated in both
      groups for 12 weeks and appropriate statistical tests were applied. RESULTS:
      Significant differences were found in the baseline characteristics and the
      postoperative changes in the eyes with and without ptosis. However, these were
      found to be transient and did not result in any new cases of amblyopia
      postoperatively. No complications requiring revision of surgery were seen.
      CONCLUSIONS: The changes in the BCSVA after frontalis brow suspension surgery are
      transient. Retinoscopy, manual keratometry, and corneal videokeratoscopy are
      simple and effective methods to evaluate the sequential refractive changes
      occurring in these eyes.

PMID- 15957480
TI  - Feasibility of screening for high-risk age-related macular degeneration with an
      Internet-based automated fundus camera.
AB  - BACKGROUND AND OBJECTIVE: The objective of this pilot study was to determine
      whether a new screening system, the DigiScope (EyeTel Imaging, Inc., Columbia,
      MD), can detect the presence of age-related macular degeneration (AMD) at a level
      requiring referral to an ophthalmologist for further evaluation and possible
      treatment. PATIENTS AND METHODS: The DigiScope is an Internet-based semi
      automated digital imaging system designed to be in primary care physicians'
      offices. Forty-two eyes of 21 patients with different categories of AMD were
      imaged with both the DigiScope and a standard color fundus camera. The imaging
      capability of the two modalities was compared for identification of lesions
      associated with AMD and classification into stages. RESULTS: There was good
      agreement for low-risk lesions and excellent agreement for high-risk lesions.
      Thirty-five of 36 eyes with intermediate or advanced disease were correctly
      identified with DigiScope images. Choroidal neovascularization was identified in
      all cases with the DigiScope due to the presence of subretinal hemorrhage or
      subretinal fibrosis. The DigiScope was found less capable of detecting subretinal
      fluid than standard stereo fundus photographs. CONCLUSIONS: This pilot study
      suggests that the DigiScope may be a useful screening tool for AMD.

PMID- 15957481
TI  - Resolution of advanced cystoid macular edema following photodynamic therapy for
      choroidal hemangioma.
AB  - A 45-year-old man was referred for 2 months of decreasing vision in his left eye.
      His visual acuity was 20/200 secondary to a subtle juxtapapillary choroidal
      hemangioma producing profound cystoid macular edema, with the affected retina
      measuring 330 microns thick by optical coherence tomography. Due to the severe
      cystoid macular edema, visual prognosis was judged to be poor. One month
      following photodynamic therapy to the tumor using verteporfin, the cystoid
      macular edema completely resolved, foveal anatomy returned to normal, optical
      coherence tomography thickness was 179 microns, and visual acuity recovered to
      20/25. Photodynamic therapy of choroidal hemangioma may be effective in resolving
      associated cystoid macular edema and improving visual acuity.

PMID- 15957482
TI  - Hypotensive retinopathy in Takayasu's arteritis.
AB  - Takayasu's arteritis could result in chronic ocular ischemia with a spectrum of
      changes that is referred to as Takayasu retinopathy. The role of an
      ophthalmologist includes photocoagulation, monitoring for complications, and
      timely referral for intervention. This article illustrates one such case that was
      effectively managed.

PMID- 15957483
TI  - Capsular phimosis following phacotrabeculectomy.
AB  - Three cases of severe capsular phimosis following augmented phacotrabeculectomy
      complicated by intense postoperative fibrinous uveitis are described. The marked
      inflammation was possibly related to the combined procedure itself, the excessive
      intraoperative manipulation to stretch the pupil, and the compromised blood
      aqueous barrier after prolonged use of pilocarpine. The combination of fibrinous
      uveitis and the small size of capsulorhexis attained through a stretched pupil
      are possible risk factors for developing severe capsular phimosis in the absence
      of zonular weakness or preoperative uveitis. For patients with similar risk
      factors, two separate surgical procedures should be considered. Alternatively, a
      larger capsulorhexis or radial relieving incisions should be attempted during
      phacotrabeculectomy to prevent this complication, which could jeopardize the
      outcome of otherwise successful surgery.

PMID- 15957484
TI  - Conjunctival squamous cell carcinoma with perineural invasion resulting in death.
AB  - Conjunctival squamous cell carcinoma is generally a low-grade malignancy. A 42
      year-old man presented with histologic evidence of extra-tumoral perineural
      invasion associated with an incompletely excised limbal conjunctival squamous
      cell carcinoma. Despite further surgery, close observation, plaque radiotherapy,
      and eyelid-sparing orbital exenteration followed by external beam radiotherapy,
      the patient developed intracranial perineural invasion with involvement of the
      trigeminal and facial nerves, ultimately resulting in death. Repeated magnetic
      resonance imaging with contrast failed to detect perineural invasion until late
      in the course of disease. Awareness of the possibility of perineural invasion in
      patients with conjunctival squamous cell carcinoma and of its aggressive nature
      may be life-saving. Nevertheless, even with initial aggressive tumor control,
      some patients will show an aggressive tumor growth with recurrences.

PMID- 15957485
TI  - "Cracked-mud" ciprofloxacin precipitates on a corneal graft.
AB  - The authors describe an extreme case of ciprofloxacin deposition on the corneal
      graft of a 67-year-old man with a history of penetrating keratoplasty for corneal
      ulcer and perforation, who presented with dense, gray deposits on the anterior
      corneal surface after being treated with ciprofloxacin for an epithelial defect.
      The deposits resolved after ciprofloxacin was discontinued. The non-physiologic
      pH of the drug formulation is thought to trigger corneal precipitates, and it
      remains to be seen whether fourth-generation fluoroquinolones will have a lower
      incidence of ocular precipitates.

PMID- 15957486
TI  - Microbial growth in various perfluorocarbon liquids.
AB  - A prospective in vitro study was conducted to investigate the potential for
      various perfluorocarbon liquids to support the growth of microbes, which may be
      introduced into these liquids as contaminants during intraocular surgery.
      Perfluorodecaline, perfluoro-noctane, and perfluorophenanthrene were tested for
      the growth of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans
      by using tryptone soy broth, pancreatic digest of casein, and Sabouraud broth as
      culture media for up to 10 days. No microbial growth was observed in any of these
      perfluorocarbon liquids. Perfluorocarbon liquids do not promote microbial growth.
      Thus, they do not increase the risk of endophthalmitis in vitreoretinal surgery.

PMID- 15957487
TI  - Treatment of juxtafoveal choroidal neovascularization with photodynamic therapy
      using verteporfin in eyes with age-related macular degeneration.
AB  - To report the results of treating juxtafoveal choroidal neovascularization with
      photodynamic therapy using verteporfin in eyes with age-related macular
      degeneration. Seven patients with predominantly classic juxtafoveal choroidal
      neovascularization were treated by photodynamic therapy using verteporfin. Three
      of the 7 patients had a gain in visual acuity and 2 had a stabilization of
      vision. The remaining 2 patients had a decrease in visual acuity. Subfoveal
      extension of the choroidal neovascularization was not observed in any patient and
      all choroidal neovascularization lesions after treatment were found to be
      nonperfused on fluorescein angiography. The encouraging results based on this
      small pilot study suggest that photodynamic therapy should be considered for
      treatment of select juxtafoveal choroidal neovascularization due to age-related
      macular degeneration.

PMID- 15957488
TI  - Fragmatome lifting: surgical option for intraocular lens and foreign body
      removal.
AB  - A new technique for intraocular lens (IOL) and foreign body removal using the
      fragmatome is described. Removal of the formed vitreous, including cortical
      vitreous, was performed using a conventional vitrectomy probe. The fragmatome tip
      was placed on the center of the anterior surface of both the IOL optics and the
      foreign bodies, and active 250 mm Hg vacuum suction was applied. IOLs and foreign
      bodies were easily held and manipulated after being aspirated into the fragmatome
      tip, avoiding the use of a forceps or other grasping instrument that may damage
      the retina. Fragmatome lifting is a reasonable treatment option for IOL and
      nonmagnetic foreign body removal.

PMID- 15957489
TI  - Secret weapon.

PMID- 15957490
TI  - Marching orders.

PMID- 15957491
TI  - Exercise time.

PMID- 15957492
TI  - The tried and true blue.

PMID- 15957493
TI  - Following the six Es.

PMID- 15957494
TI  - Seated impact.

PMID- 15957495
TI  - Grassroots mobility.

PMID- 15957496
TI  - The LTACH in rehab clothing.

PMID- 15957497
TI  - Improvements government style.

PMID- 15957498
TI  - Low-level laser therapy.

PMID- 15957499
TI  - Inpatient rehabilitation at the crossroads.

PMID- 15957500
TI  - [Selection from the 19th century Hungarian dental literature. Part I. 1800-1900].
AB  - The selection was made from the 19th century dental literature according to the
      viewpoint of the author. Several scientifically found books were published
      alongside the earlier popular ones which served the education of the population
      at large. Those scholarly works served as the scientific background for the
      dental literature at the end the 19th century when proper medical training in
      dentistry was established.

PMID- 15957501
TI  - [Caries and periodontal state of pregnant women. Part I. Caries status].
AB  - A misconception exists in the society regarding the caries frequency during
      pregnancy. The condition of the teeth of the child can be influenced by the state
      of the teeth and the oral hygiene habits of the mother. An examination was
      conducted among young women soon after delivery in Szeged/Hungary. The number of
      the examined patients was 161, with the average age of 27.6 years. The DMFT
      (Decayed, Missing, Filled Teeth) index was 12.45, while the DMFS (Decayed,
      Missing, Filled Surfaces) index was 26.07 in the examined population. The DMFT
      index significantly correlated with age, number of pregnancies, plaque index,
      probing pocket depth and bleeding on probing, while the DMFT index was not
      dependent on education level, profession and place of residency. There was no
      significant correlation between the number of previous pregnancy and the
      incidence of caries.

PMID- 15957502
TI  - [Role of the dentist in the reduction of oral complications caused by
      radiotherapy in head and neck cancer].
AB  - The treatment of head and neck cancer patients using radiotherapy precipitates
      has many oral side effects that can lead to serious local and systemic
      complications. A comprehensive system of oral health care management is necessary
      to prevent or limit some serious side effects as well as the provision of
      palliative treatment for other unavoidable oral complications. It is essential
      that the dentist's treatment plan be adapted to meet individual needs of each
      patient. The basis for this plan should include a diagnosis as to the extent of
      the disease and its prognosis; the radiation field and anticipated extent of
      surgical and/or chemo-therapeutic intervention; and the patients subsequent
      compliance with recommendations. While considering the literature relative to
      this subject, this paper also summarizes treatment protocols that are observed by
      the University of Szeged School of Dentistry for those tumor patients who have
      undergone radiotherapy, in a country, where the incidence statistics for head and
      neck tumor mortality and morbidity continue to rank among the world's highest.

PMID- 15957503
TI  - Longitudinal single-cell cytokine responses reveal recurrent autoimmune myelin
      reactivity in relapsing--remitting multiple sclerosis patients.
AB  - The relationship between multiple sclerosis (MS) disease activity and myelin
      protein-induced cytokine responses over time is not elucidated. We addressed this
      relationship by examining longitudinal cytokine responses to myelin proteins
      every three months for one year, in the context of gadolinium (gad)-enhancing
      brain lesions and of clinical relapses. The ELISPOT assay was used to determine
      the ex vivo cytokine production in response to nine amino acid long peptides
      spanning the entire proteolipid protein (PLP) and myelin basic protein (MBP)
      molecules in relapsing-remitting (RR) MS patients and matched healthy controls.
      We identified three longitudinal levels of myelin-induced cytokine secretion by
      adding up the positive responses for all PLP or MBP peptides obtained for five
      timepoints, at three-month intervals: low reactivity (< 200 cumulative cytokine
      secreting cells), isolated peptide reactivity (201-450 cumulative cytokine
      secreting cells) and recurrent protein-wide bursts of cytokine reactivity (> 451
      cumulative cytokine-secreting cells). The majority of MS patients showed
      recurrent bursts to PLP and MBP. In contrast, controls showed a more even
      distribution between all levels of cytokine reactivity. The majority of patients
      with gad-enhancing lesions showed PLP/IFN gamma and MBP/IFN gamma recurrent burst
      responses. This is the first longitudinal study on MS patients in which nine
      amino acid long myelin peptides are used to reveal the broad range of PLP- and
      MBP-peptide cytokine reactivity across the whole molecule of these two major
      myelin proteins. This study also reveals the extremely dynamic nature of the
      immune reactivity to numerous regions of myelin, which can fluctuate dramatically
      over time. Such fluctuation could hamper the efficacy of antigen-based therapies
      for MS.

PMID- 15957505
TI  - 25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis.
AB  - Past sun exposure and vitamin D supplementation have been associated with a
      reduction in the risk of MS. We measured the serum concentration of 25
      hydroxyvitamin D (25[OH]D) at the time of MS diagnosis in 40 MS patients and 40
      controls. We found no difference in the serum levels of 25(OH)D between MS
      patients and controls when all samples or samples obtained during winter months
      were compared, but MS patients had significantly lower serum 25(OH)D
      concentrations in June to September than the controls. The vitamin D stores were
      adequate for bone metabolism (> 37 nmol/L) in 70% of MS patients throughout the
      year and within the hypovitaminosis level (< 37 nmol/L) in 30% of MS patients at
      some time of the year. During MS-relapses, 25(OH)D levels were lower than in
      remission, but mostly within the reference range observed in relation with normal
      bone metabolism. We conclude that the vitamin D stores in most MS patients are
      adequate for their normal bone metabolism. However, lower vitamin D levels during
      MS relapses than in remission suggest that vitamin D could be involved in the
      regulation of the clinical disease activity of MS. The optimal serum levels of
      vitamin D for the regulation of immune responses remain to be determined.

PMID- 15957504
TI  - Tau protein level in cerebrospinal fluid is increased in patients with early
      multiple sclerosis.
AB  - Axonal damage has been proposed as the major substrate of permanent clinical
      disability in multiple sclerosis. Tau protein, a microtubule-associated protein
      localised in neuronal axons, may serve as a biochemical surrogate marker to
      evaluate axonal damage in vivo. We intended to determine the extent of axonal
      damage in different stages and clinical subtypes of MS by investigating
      cerebrospinal fluid tau concentrations. Tau was measured using an immunoassay in
      35 patients with relapsing-remitting MS, eight patients with secondary
      progressive MS, nine patients with primary progressive MS, 50 patients with
      clinically isolated syndrome suggestive of early MS and 46 normal controls.
      Cerebrospinal fluid tau was significantly elevated in MS compared with normal
      controls (median 206.0 pg/mL versus 152.0 pg/mL; P = 0.002). No significant
      difference among different subtypes of MS could be detected, although highest
      levels were found in very early disease stages. There was a significant elevation
      of CSF tau among patients with gadolinium-enhancing brain lesions in magnetic
      resonance imaging (P = 0.02) and a tendency towards higher CSF tau levels in
      patients with pronounced intrathecal IgG synthesis, supporting the notion that
      axonal damage is influenced by inflammatory activity.

PMID- 15957506
TI  - Serum ferritin, transferrin and soluble transferrin receptor levels in multiple
      sclerosis patients.
AB  - Over the last few years, increased evidence has supported the role of iron
      dysregulation in the pathogenesis of multiple sclerosis (MS), as iron is
      essential for myelin formation and oxidative phosphorylation. We studied indices
      of iron metabolism, such as serum iron, ferritin, transferrin and soluble
      transferrin receptor (sTFR) levels in 27 MS patients. Seven patients had chronic
      progressive active disease (CP-A), six had chronic progressive stable (CP-S), ten
      had relapsing remitting active (RR-A) and four had relapsing-remitting stable (RR
      S) disease. sTFR levels were found to be significantly higher in CP-A (P = 0.021)
      and RR-A (P < 0.004) patients than in controls. sTFR levels were also elevated in
      CP-S patients but did not reach significance (P = 0.064). sTFR values in RR-S
      patients were comparable to those found in controls (P = 0.31). Ferritin levels
      were significantly elevated only in CP-A patients (P < 0.002). Patients of the CP
      group had significantly higher ferritin values than the RR patients (P < 0.004).
      Haemoglobin values as well as iron and transferrin levels were within normal
      limits in all patients. In conclusion, the increased serum sTFR and ferritin
      levels in nonanaemic MS patients with active disease reflect the increased iron
      turnover. The mild elevation of sTFR levels in CP-S patients may indicate active
      inflammation with ongoing oxidative damage that is not detectable by history or
      examination.

PMID- 15957507
TI  - Emergence of thalamic magnetization transfer ratio abnormality in early relapsing
      remitting multiple sclerosis.
AB  - While there is now evidence for thalamic abnormality in established secondary
      progressive and relapsing-remitting multiple sclerosis (MS), it remains unclear
      when such abnormality begins. This study investigated the emergence of thalamic
      abnormality in relapsing-remitting MS by assessing the thalamic magnetization
      transfer ratio (MTR) in a cohort with clinically early disease. Twenty-three
      patients with early relapsing-remitting MS (mean age 37; mean disease duration
      1.9 years; Expanded Disability Status Scale (EDSS) range 0-3) and 19 healthy
      controls (mean age 34) were imaged yearly with a magnetization transfer imaging
      sequence. Twenty-two MS patients and 14 controls completed two-year follow-up.
      Regions of interest were placed in both thalami and mean thalamic MTR calculated.
      At baseline, significant differences between patient and control thalamic MTR
      were not observed. However, at years one and two, the thalamic MTR in patients
      was significantly lower than control MTR. Although baseline lesion volume did not
      correlate with baseline thalamic MTR, at year one, an association between
      baseline lesion volume and year one thalamic MTR emerged. There was also a
      significant inverse correlation between EDSS and thalamic MTR (r = -0.47, P =
      0.02). The study suggests that thalamic involvement occurs within the first five
      years of MS onset, when most patients are still minimally disabled.

PMID- 15957508
TI  - Trigeminal involvement in multiple sclerosis: magnetic resonance imaging findings
      with clinical correlation in a series of patients.
AB  - Trigeminal involvement detected by magnetic resonance imaging (MRI) in multiple
      sclerosis (MS) patients is usually associated with trigeminal neuralgia (TN) or
      painless paraesthesia in the trigeminal distribution. Our aim is to review the
      incidence of trigeminal involvement on MRI in a series of patients with MS at our
      institution, with further clinical correlation. We reviewed MRI scans of 275 MS
      patients for the presence of gadolinium enhancement on postcontrast T1-weighted
      images, anatomical and signal abnormalities on different sequences at the pontine
      trigeminal root entry zone (REZ) and in the cisternal portion of the nerves. We
      observed enhancement in the cisternal portion of the nerves and signal
      abnormalities (with or without enhancement) at the pontine trigeminal REZ in 8
      (2.9%) patients, and enhancement was bilateral in 6 (75%) of those. Despite the
      inflammatory activity, none of them had TN and 3 (37.5%) had only painless
      paraesthesias in the correspondent V3 distribution. We also found a marked
      trigeminal hypertrophy in 2 (25%) patients, both with a longer period of disease.
      Our results confirm a high and clinically silent incidence of trigeminal
      involvement in MS patients, and suggest a simultaneous role of the central and
      peripheral type of myelin in trigeminal demyelination.

PMID- 15957509
TI  - A randomized clinical trial of valacyclovir in multiple sclerosis.
AB  - OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple
      sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety
      profile. A two-year placebo-controlled, double-blind study was conducted to (1)
      ascertain if high-dose, prolonged treatment with valacyclovir would be safe and
      (2) observe if valacyclovir would delay the progression of MS clinically or by
      magnetic resonance imaging (MRI). DESIGN/METHODS: Fifty-eight patients were
      stratified as to severity and randomly assigned to receive valacyclovir (3000
      mg/day) or placebo for a period of two years. Patients were followed clinically
      over the two-year period by means of the Expanded Disability Status Scale (EDSS),
      the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab
      studies every three months. Patients continued on the medication for two years
      unless they had a sustained progression or repeated exacerbations. RESULTS: No
      patient discontinued the study due to side effects or toxicity. In Relative
      Ranking of Progression, time to first attack, attack rate, and time to withdrawal
      there were trends (but not statistically significant) toward drug effect over
      placebo in the Severe clinical category. MRI evaluation showed no significant
      drug effect. CONCLUSIONS: Although not statistically significant, positive trends
      were detected for acyclovir by clinical measures, but not by MRI.

PMID- 15957510
TI  - A pilot trial of combination therapy with mitoxantrone and interferon beta-1b
      using monthly gadolinium-enhanced magnetic resonance imaging.
AB  - OBJECTIVE: To examine the safety of combination therapy with mitoxantrone (MITX)
      and interferon beta-1b (IFNbeta-1b) in patients with multiple sclerosis (MS) and
      a high on-therapy relapse rate and enhancing lesions on baseline magnetic
      resonance imaging (MRI) scan. METHODS: Ten patients with worsening relapsing
      remitting or secondary progressive MS were studied using monthly MRI with triple
      dose gadolinium contrast. All patients must have been on IFNbeta-1b for at least
      six months, have at least one enhancing lesion on a screening MRI, at least one
      relapse on IFNbeta-1b in the six months prior to study entry and be neutralizing
      antibody negative. Monthly MRI scans using triple dose contrast and a 30-minute
      delay between contrast administration and scanning were carried out three times
      over two months to obtain baseline numbers of enhancing lesions each month. At
      the end of the baseline phase, MITX was administered at 12 mg/m2 (month 3), and 5
      mg/m2 at months 4 and 5. Dosing was continued at 5 mg/m2 every third month.
      Monthly MRI scanning was continued throughout the duration of MITX dosing. The
      primary outcome measure was the frequency of new enhancing lesions. Secondary
      outcome measures included relapse rate, and T1 hypointense and T2 lesion burden.
      RESULTS: Following the addition of MITX to IFNbeta-1b mean enhancing lesion
      frequency decreased 90% at month 7 (P = 0.008) and enhancing lesion volume
      decreased by 96% (P = 0.01). Relapse rates decreased 64% (P = 0.004). T2 lesion
      burden and T1 hypointense lesion burden increased slightly during the baseline
      phase and decreased following MITX but the difference did not reach statistical
      significance. There were no serious adverse events on combination therapy and no
      drop-outs due to toxicity. Total white blood cell count was reduced at 14 days
      post-MITX infusion but returned to normal levels by day 21. There were no
      neutropenic fevers and there was no clinically significant elevation of liver
      function tests. CONCLUSIONS: While the number of patients in this study was
      small, the results suggest that the combination is safe and well tolerated.
      Disease activity was substantially reduced following the addition of MITX to
      IFNbeta-1b.

PMID- 15957511
TI  - Effect of pulsed magnetic field therapy on the level of fatigue in patients with
      multiple sclerosis--a randomized controlled trial.
AB  - Twenty-five multiple sclerosis patients, taking part in a rehabilitation program,
      were randomly assigned to treatment with pulsed magnetic field therapy (PMFT) or
      to sham therapy in order to study the additional effect of PMFT as part of a
      multimodal neurological rehabilitation program on fatigue. Patients demographic
      and disease specific characteristics were recorded. Level of fatigue was measured
      by fatigue severity scale (FSS) at entrance and discharge and with a visual
      analog scale (VAS) immediate before and after a single treatment session. The
      'Magnetic Cell Regeneration' system by Santerra was used for PMFT. A single
      treatment lasted 16 minutes twice daily over 3-4 weeks and consisted of relaxed
      lying on a PMF mattress. Sham intervention was conducted in an identical manner
      with the PMF-device off. Patients and statistics were blinded. Level of fatigue
      measured by FSS was high at entrance in both treatment group (TG) and control
      group (CG) (5.6 versus 5.5). Over time of rehabilitation fatigue was reduced by
      18% in TG and 7% in CG which was statistically not significant. There was a
      statistically significant immediate effect of the single treatment session which
      18% reduction of fatigue measured by VAS in TG versus 11% in CG. Because of a
      high 'placebo effect' of simple bed rest, a only small and short lasting
      additional effect of PMFT and high costs of a PMF-device, we cannot recommend
      PMFT as an additional feature of a multimodal neurological rehabilitation program
      in order to reduce fatigue level of MS-patients.

PMID- 15957512
TI  - Factors related with treatment adherence to interferon beta and glatiramer
      acetate therapy in multiple sclerosis.
AB  - BACKGROUND: Awareness of the factors influencing discontinuation of
      immunomodulatory drugs (IMD) treatment in multiple sclerosis (MS) can help to
      find approaches to patient management with the aim of establishing more specific
      indications and also attaining more optimal patient selection in future clinical
      trials. OBJECTIVE: To identify the causes that influence adhesion to IMD therapy
      within the clinical practice in a large cohort of patients with MS. PATIENTS AND
      METHODS: We have studied all MS patients who have initiated IMD in our hospital.
      All patients took part in training sessions where treatment expectations and side
      effects were explained and they received training in the administration
      technique. Reasons for stopping therapy were recorded during follow-up. RESULTS:
      We studied 632 MS patients (mean follow-up was 47.1 (28.7) months). At the time
      of analysis, 107/632 patients (17%) were no longer receiving IMD. Almost half of
      the patients who stopped IMD (52/107) did so within the first two years on
      therapy. Fifty-six patients stopped IMD because of lack of efficacy. Only 27
      patients (4.3%) discontinued treatment for reasons other than inefficacy or side
      effects. The proportion of patients with secondary progressive MS that stopped
      IMD therapy was 30%, while only 13.5% of the patients with relapsing remitting MS
      stopped therapy (P < 0.0001). Expanded Disability Status Scale (EDSS) score at
      entry was the main factor that predicted interruption of therapy. CONCLUSIONS:
      The proportion of patients interrupting IMD in our centre is low, possibly due to
      individualized care. Higher EDSS, mainly in the first two years of treatment, is
      the main factor related with interruption. Close follow-up of these patients
      would be useful in avoiding early discontinuation of therapy.

PMID- 15957513
TI  - Elevated endothelial microparticle-monocyte complexes induced by multiple
      sclerosis plasma and the inhibitory effects of interferon-beta 1b on release of
      endothelial microparticles, formation and transendothelial migration of monocyte
      endothelial microparticle complexes.
AB  - Monocyte migration through the disrupted cerebral endothelial cell (EC) junctions
      plays an essential role in formation of multiple sclerosis (MS) demyelinating
      lesions. During pathogenesis of MS, activated ECs release endothelial
      microparticles (EMP), which possibly facilitate transendothelial migration
      (TEMIG) of monocytes. To assess functional roles of EMP in MS, specifically,
      their (i) interaction with monocytes, (ii) effect on monocyte TEMIG in an in
      vitro model of the brain microvascular endothelial cells (BMVEC), (iii)
      phenotypic profiles of EMP elicited by MS plasma and (iv) the effects of IFN-beta
      1b on release of EMP and on TEMIG of monocytes (mono) and monocytes:EMP complexes
      (mono:EMP) through the BMVEC. The effect of IFN-beta 1b on the release of EMP and
      the TEMIG of mono and mono:EMP was assessed by preincubating BMVEC cultures of
      IFN-beta 1b prior to addition of plasma. Three EMP phenotypes, CD54, CD62E and
      CD31 were assayed. Plasma specimens from 20 patients with relapsing remitting MS
      (11 in exacerbation, MS-E, and 9 in remission, ME-R) and 10 healthy controls were
      studied. Incubation of BMVEC with MS-E plasma yielded elevated levels of EMPCD54,
      EMP62E and EMPCD31 relative to MS-R and control plasmas. MS-E but not MS-R or
      control plasma also augmented TEMIG of monocytes, respectively. Mono:EMP
      complexes further augmented TEMIG relative to mono alone, but only in the
      presence of MS-E plasma; there was no significant effect with MS-R or control
      plasmas. The presence of IFN-beta 1b inhibited TEMIG of mono and mono:EMP by 20%
      and 30%, respectively. MS-E but not MS-R plasma elicited release of activation
      derived EMP and enhanced TEMIG of mono and mono:EMP. IFN-beta 1b inhibited TEMIG
      and release of EMP, suggesting a role of EMP and a novel therapeutic mechanism
      for IFN-beta 1b in MS.

PMID- 15957514
TI  - Motor cortex excitability and fatigue in multiple sclerosis: a transcranial
      magnetic stimulation study.
AB  - We investigated electrophysiological correlates of fatigue in patients with
      multiple sclerosis (MS). Transcranial magnetic stimulation (TMS) was used to
      explore motor excitability in three groups of subjects: MS patients with fatigue
      (MS-F), MS patients without fatigue (MS-NF) and healthy control subjects. All
      participants had to perform a fatiguing hand-grip exercise. TMS was performed
      prior to and after the exercise. Prior to the motor task, MS-F patients had less
      inhibition in the primary motor cortex compared to both other groups.
      Postexercise, intracortical inhibition was still reduced in the MS-F patients
      compared to the MS-NF patients. In MS-F patients the postexercise time interval
      for normalization of the motor threshold was correlated with the fatigue
      severity. We conclude that MS patients with fatigue have an impairment of
      inhibitory circuits in their primary motor cortex. The results also indicate that
      fatigue severity is associated with an exercise-induced reduction of membrane
      excitability.

PMID- 15957515
TI  - Severity of chronic pain and its relationship to quality of life in multiple
      sclerosis.
AB  - INTRODUCTION: This study used reliable and validated instruments to compare pain
      severity in multiple sclerosis (MS) to that in other chronic painful conditions,
      and to examine relationships between chronic pain in MS and health-related
      quality of life (HRQOL). METHODS: Ninety-nine MS patients completed a self
      administered survey comprised of the Medical Outcomes 36-Item Short-Form Health
      Survey, the Short-Form McGill Pain Questionnaire, and the Hospital Anxiety and
      Depression Scale. RESULTS: Pain severity was not different between MS patients
      with pain and rheumatoid arthritis (P = 0.77) or osteoarthritis (P = 0.98)
      patients. Chronic pain in MS was less often neurogenic than non-neurogenic,
      although severity of neurogenic pain was greater than that of non-neurogenic pain
      (P = 0.048). Chronic pain in MS was found to have no significant relationship to
      age, disease duration or disease course. Instead, we found that pain was
      correlated with aspects of HRQOL, particularly mental health (r = 0.44, P <
      0.0001) versus physical functioning (r = 0.19, P > 0.05). Chronic pain was
      significantly related to anxiety and depression for females but not for males
      with MS. CONCLUSIONS: Chronic pain in MS is as severe as pain in arthritic
      conditions and is associated with reduced HRQOL. Thus, pain can be a significant
      symptom for MS patients and the need for treatment may be underestimated.

PMID- 15957516
TI  - The Goldman Consensus statement on depression in multiple sclerosis.
AB  - BACKGROUND: In January 2002 the New York City Chapter of the National Multiple
      Sclerosis Society convened a panel of experts to review the issue of depressive
      affective disorders associated with multiple sclerosis (MS). This Consensus
      Conference was supported by a grant from the Goldman family of New York City.
      RESULTS: The panel reviewed summaries of current epidemiologic, neurobiologic,
      and therapeutic studies having to do with depressive disorders among MS patient
      populations. Depressive disorders occur at high rates among patients with MS, and
      there is reason to believe that the immunopathology of the disease is involved in
      the clinical expression of affective disorders. The depressive syndromes of MS
      have a major, negative impact on quality of life for MS sufferers, but are
      treatable. At the present time, most MS patients with depression do not receive
      adequate recognition and treatment. CONCLUSIONS: The Goldman Consensus Conference
      Study Group provides recommendations for improved screening, diagnosis, and
      clinical management for depressive affective disorders among patients suffering
      from MS.

PMID- 15957517
TI  - Validation of the NARCOMS Registry: pain assessment.
AB  - The North American Research Committee on Multiple Sclerosis (NARCOMS) Registry is
      a multiple sclerosis (MS) self-report registry with more than 24,000
      participants. Participants report disability status upon enrollment, and semi
      annually using Performance Scales (PS), Patient Determined Disease Steps (PDDS)
      and a pain question. In November 2000 and 2001, we also collected the Pain
      Effects Scale (PES). Our aim was to validate the NARCOMS pain question using the
      PES as our criterion measure. We measured correlations between the pain question
      and age, disease duration, various PS subscales and PDDS to assess construct
      validity. We correlated pain question responses in participants who reported no
      change in PDSS or the PS subscales between questionnaires to determine test
      retest reliability. We measured responsiveness in participants who reported a
      substantial change in the sensory, spasticity PS subscales. The correlation
      between the pain question and PES was r = 0.61 in November 2000, and r = 0.64 in
      November 2001 (both P < 0.0001). Correlations between the pain question and age,
      and disease duration were low, indicating divergent validity. Correlations
      between the pain question and spasticity, sensory PS subscales and PDSS were
      moderate, indicating convergent validity. Test-retest reliability was r = 0.84 (P
      < 0.0001). Responsiveness was 70.7%. The pain question is a valid self-report
      measure of pain in MS.

PMID- 15957518
TI  - Accuracy of two electronic pedometers for measuring steps taken under controlled
      conditions among ambulatory individuals with multiple sclerosis.
AB  - Pedometers are inexpensive and user-friendly devices that might be practical for
      measuring physical activity among individuals with multiple sclerosis (MS). This
      study involved an evaluation of the accuracy of two pedometers against actual
      steps taken under controlled laboratory conditions (five minute bouts of walking
      at five different treadmill speeds [41, 54, 67, 80, and 94 m x min(-1)]) among 23
      individuals with MS who were ambulatory without an aide. Both pedometers
      exhibited good accuracy with the 67, 80, and 94 m x min(-1) speeds, but poor
      accuracy with the 41 and 54 m x min(-1) speeds. Those results support the
      quantification of physical activity using pedometers among those with MS who are
      ambulatory without an aide.

PMID- 15957519
TI  - Successful pregnancy of a patient with Balo's concentric sclerosis.
AB  - Balo's concentric sclerosis is a severe demyelinating disease with poor
      prognosis. To date, nothing is known about the effects of pregnancy on the course
      of Balo's disease. We describe here the first successful pregnancy of a patient
      with Balo's concentric sclerosis. Upon neurological worsenings during pregnancy,
      our patient was treated with high-dose methylprednisolone and plasma-exchange.
      Intravenous immunoglobulin and interferon-beta-1a were given postpartum. At the
      last follow-up visit 2.5 years after the delivery the patient had only minor
      residual symptoms.

PMID- 15957520
TI  - The influence of sex hormones on cytokines in multiple sclerosis and experimental
      autoimmune encephalomyelitis: a review.
AB  - The female predominance of multiple sclerosis (MS) has suggested that hormonal
      differences between the sexes must confer some protective effect on males or
      enhance the susceptibility of females to this disease. There has been evidence
      that gonadal hormones can modulate the immune response regulated by antigen
      presenting cells and T cells. These cells control the immune response by the
      production of interacting pro- and anti-inflammatory cytokines. The first include
      the acute phase pro-inflammatory cytokines of the innate immune response as well
      as the T-helper 1 (Th1) cytokines, while the later contain the Th2 cytokines as
      well as the suppressor cytokines. There is some evidence that MS and experimental
      autoimmune encephalitis (EAE) are Th1 cell-mediated diseases. For this reason
      many studies have been done to influence the pro-inflammatory cytokine production
      of these Th1 cells in favour of an anti-inflammatory immune response as mediated
      by Th2 cells. However the role of the regulatory T cells in this context is not
      clearly understood. Here we review the studies concerning the role of sex
      hormones on the cytokine production in relation to the disease course of MS and
      EAE and in particular in the light of the recent revival of the regulatory T
      cells and their suppressive cytokines.

PMID- 15957521
TI  - One-year cyclophosphamide treatment combined with methylprednisolone improves
      cognitive dysfunction in progressive forms of multiple sclerosis.
AB  - We conducted an evaluation of changes in cognition in progressive multiple
      sclerosis (MS) patients receiving monthly intravenously pulse of cyclophosphamide
      (700 mg/m2) with methylprednisolone (1g). Twenty-eight consecutive progressive MS
      patients (10 primary progressive, 18 secondary progressive MS) were evaluated
      before and after six and 12 months of treatment. The WAIS-R score, memory and
      executive functions were evaluated. Under treatment we found a significant
      improvement in global cognitive efficiency, encoding abilities, planning
      abilities and inhibition after six and 12 months. However, mechanisms of action
      of the positive effect of these anti-inflammatory and immunosuppressive
      treatments on cognition remain unclear.

PMID- 15957522
TI  - Hereditary Melkersson-Rosenthal syndrome and multiple sclerosis.
AB  - The revision of MEDLINE from 1966 to 2003 did not report any association between
      multiple sclerosis (MS) and Melkersson-Rosenthal syndrome (MRS). This is a case
      report of a 51-year-old woman, with history of four recurrent Bell's palsies. In
      1999 she developed a right facial paralysis due to a supranuclear pyramidal
      lesion with right monoparesis. The family history showed five relatives with
      recurrent Bell's paralysis and plicata tongue. PHYSICAL EXAMINATION: right Bell's
      paralysis, left supranuclear facial paralysis, furrowed tongue, right hemiparesis
      with pallor of the optic disks. Brain magnetic resonance imaging (MRI)
      demonstrated the typical lesions of MS and CSF oligoclonal bands. This is the
      first observation of a patient with hereditary MRS and MS. The link between both
      diseases is discussed.

PMID- 15957523
TI  - Autologous stem cell transplantation as rescue therapy in malignant forms of
      multiple sclerosis.
AB  - Malignant forms of multiple sclerosis (MS) represent a limited group of very
      aggressive demyelinating diseases, which rapidly progress to severe disability
      leading often to life-threatening conditions. On these clinical entities,
      currently available therapies for MS are not very effective. Recently, it has
      been demonstrated that intense immunosuppression followed by autologous stem cell
      transplantation (ASCT) can affect the clinical course of individuals with severe
      MS and completely abrogate the inflammatory activity detected by magnetic
      resonance imaging (MRI). We report on the treatment with intense immune ablation
      followed by ASCT of three patients with malignant MS whose clinical course
      indicated a dramatically poor prognosis. This procedure succeeded in halting the
      rapidly worsening course of disease. The effect was long lasting, as demonstrated
      by a sustained efficacy over a two-year period in two subjects and 12 months in
      the third case. In addition, a striking effect on inflammation-related MRI
      findings was obtained. These results support a role for intense immunosuppression
      followed by ASCT as treatment in rapidly evolving malignant MS cases unresponsive
      to conventional therapies.

PMID- 15957524
TI  - [Nobel prize in chemistry, degradation system and cellular protein].

PMID- 15957525
TI  - [Immunostimulatory properties of CpG sequences in bacterial DNA].

PMID- 15957526
TI  - [The penicillin-binding proteins and their role in physiological processes of
      gram-negative bacteria on the example of Escherichia coli].

PMID- 15957527
TI  - [Protein isoprenylation].

PMID- 15957528
TI  - [The inhibition of apoptosis in cancer cells resistant to anticancer drugs].

PMID- 15957529
TI  - [Apolipoprotein E--the role of polymorphism in pathogenesis of many diseases].

PMID- 15957530
TI  - [Purine nucleotides of human erythrocytes--metabolism and regulation].

PMID- 15957531
TI  - [Glutamine transport in the central nervous system].

PMID- 15957532
TI  - [DNA microarray technology in large-scale analysis of changes in plant gene
      expression profile in response to changing environmental conditions].

PMID- 15957533
TI  - [Aquaporins--new entry into plants water movement].

PMID- 15957534
TI  - [Muscle and cell motility: from cell physiology to human pathology].

PMID- 15957535
TI  - [Modified nucleic acids. 100th anniversary of the birth of prof. Bronislaw
      Filipowicz. Conference report].

PMID- 15957536
TI  - Evidence-based toxicology: a comprehensive framework for causation.
AB  - This paper identifies deficiencies in some current practices of causation and
      risk evaluation by toxicologists and formulates an evidence-based solution. The
      practice of toxicology focuses on adverse health events caused by physical or
      chemical agents. Some relations between agents and events are identified risks,
      meaning unwanted events known to occur at some frequency. However, other
      relations that are only possibilities--not known to occur (and may never be
      realized)--also are sometimes called risks and are even expressed quantitatively.
      The seemingly slight differences in connotation among various uses of the word
      'risk' conceal deeply philosophic differences in the epistemology of harm. We
      label as 'nomological possibilities' (not as risks) all predictions of harm that
      are known not to be physically or logically impossible. Some of these nomological
      possibilities are known to be causal. We term them 'epistemic'. Epistemic
      possibilities are risks. The remaining nomological possibilities are called
      'uncertainties'. Distinguishing risks (epistemic relationships) from among all
      nomological possibilities requires knowledge of causation. Causality becomes
      knowable when scientific experiments demonstrate, in a strong, consistent
      (repeatable), specific, dose-dependent, coherent, temporal and predictive manner
      that a change in a stimulus determines an asymmetric, directional change in the
      effect. Many believe that a similar set of characteristics, popularly called the
      'Hill Criteria', make it possible, if knowledge is robust, to infer causation
      from only observational (nonexperimental) studies, where allocation of test
      subjects or items is not under the control of the investigator. Until the 1980s,
      medical decisions about diagnosis, prevention, treatment or harm were often made
      authoritatively. Rather than employing a rigorous evaluation of causal
      relationships and applying these criteria to the published knowledge, the field
      of medicine was dominated by authority-based opinions, expressed by experts (or
      consensus groups of experts) relying on their education, training, experience,
      wisdom, prestige, intuition, skill and improvisation. In response, evidence-based
      medicine (EBM) was developed, to make a conscientious, explicit and judicious use
      of current best evidence in deciding about the care of individual patients. Now
      globally embraced, EBM employs a structured, 'transparent' protocol for carrying
      out a deliberate, objective, unbiased and systematic review of the evidence about
      a formally framed question. Not only in medicine, but now in dentistry,
      engineering and other fields that have adapted the methods of EBM, it is the
      quality of the evidence and the rigor of the analysis through evidence-based
      logic (EBL), rather than the professional standing of the reviewer, that leads to
      evidence-based conclusions about what is known. Recent studies have disclosed
      that toxicologists (individually or in expert groups), not unlike their medical
      counterparts prior to EBM, show distressing variations in their biases with
      regard to data selection, data interpretation and data evaluation when performing
      reviews for causation analyses. Moreover, toxicologists often fail to acknowledge
      explicitly (particularly in regulatory and policy-making arenas) when
      shortcomings in the evidence necessitate reliance upon authority-based opinions,
      rather than evidence-based conclusions (Guzelian PS, Guzelian CP. Authority-based
      explanation. Science 2004; 303: 1468-69). Accordingly, for answering questions
      about general and specific causation, we have constructed a framework for
      evidence-based toxicology (EBT), derived from the accepted principles of EBM and
      expressed succinctly as three stages, comprising 12 total steps. These are: 1)
      collecting and evaluating the relevant data (Source, Exposure, Dose, Diagnosis);
      2) collecting and evaluating the relevant knowledge (Frame the question, Assemble
      the relevant (delimited) literature, Assess and critique the literature); and 3)
      Joining data with knowledge to arrive at a conclusion (General causation--answer
      to the framed question, Dose-response, Timing, Alternative cause, Coherence). The
      second of these stages (which amounts to an analysis of general causation), is
      addressed by an EBM-styled approach (adapted for the infrequent availability of
      human experimental studies in environmental toxicology). This involves assembling
      literature (through documented algorithms for database queries), excluding
      irrelevancies by use of delimiters as filters, and ranking and rating the
      remaining articles for strength of study design and for quality of execution
      gauged by application of either a ready-made quality assessment instrument or a
      custom designed checklist or scale. The results of this systematic review
      (including a structured review of relevant animal and in vitro studies) are then
      themselves systematically used to determine which causation criteria are
      fulfilled. Toxicology is maturing from a derivative science largely devoted to
      routinized performance and interpretation of safety tests, to a discipline deeply
      enmeshed in the remarkable advances in biochemistry and molecular biology to
      better understanding the nature and mechanism of adverse effects caused by
      chemicals. It is time for toxicologists, like scientists in other fields, to
      formalize a method for differentiating settled toxicological knowledge of risk
      from mere nomological possibility, and for communicating their conclusions to
      other scientists and the public. It is time for EBT.

PMID- 15957537
TI  - Protein kinase C and chemical-induced abnormal palate development.
AB  - The protein kinase C (PKC) family of proteins mediates the action of growth
      factors and other ligands by activating a network of transcription factors that
      bind to TRE sequences in the promoters of many genes that regulate cell
      proliferation, differentiation, extracellular matrix synthesis, apoptosis and
      others in a cell type-, isozyme- and context-specific manner. The critical role
      of PKC in embryonic development is indicated by early death of embryos in which
      one or more of these isozymes are inactivated. Our studies together with others
      show that palatal PKC signalling is functional and may be essential for normal
      palate development. Although single gene knockouts have failed to exhibit the
      cleft palate (CP) phenotype, owing to compensation by other kinases, many
      chemicals including the mycotoxin, secalonic acid D, disrupt palatal PKC
      signalling leading to altered palatal mesenchymal gene expression. The potential
      relevance of such effects to chemical-induced CP is discussed.

PMID- 15957538
TI  - Successful treatment of acute aluminium phosphide poisoning: possible benefit of
      coconut oil.
AB  - Aluminium phosphide is used to control rodents and pests in grain storage
      facilities. It produces phosphine gas, which is a mitochondrial poison.
      Unfortunately, there is no known antidote for aluminium phosphide intoxication,
      but our recent experience with a case showed that rapid prevention of absorption
      by coconut oil might be helpful. In the present case, we used the same protocol
      in a 28-year-old man who had ingested a lethal amount (12 g) of aluminium
      phosphide with suicidal intent and was admitted to hospital approximately 6 hours
      postingestion. The patient had signs and symptoms of severe toxicity, and his
      clinical course included metabolic acidosis and liver dysfunction. Treatment
      consisted of gastric lavage with potassium permanganate solution, oral
      administration of charcoal and sorbitol suspension, intravenous administration of
      sodium bicarbonate, magnesium sulphate and calcium gluconate, and oral
      administration of sodium bicarbonate and coconut oil. Conservative and supportive
      therapy in the Intensive Care Unit was also provided. The patient survived
      following rapid treatment and supportive care. It is concluded that coconut oil
      has a positive clinical significance and can be added to the treatment protocol
      of acute aluminium phosphide poisoning in humans.

PMID- 15957539
TI  - Can cystatin C be a better marker for the early detection of renal damage in
      primary hypertensive patients?
AB  - In this study, we aimed to compare Cystatin C (Cys C) with other traditional
      glomerular filtration rate (GFR) markers and to evaluate its superiority over
      them in detecting early renal involvement in patients with primary hypertension.
      Fifty-one primary hypertensive patients and 29 healthy control subjects, who were
      similar in terms of age and gender, were included in the study. In all subjects
      serum levels of Cys C, beta-2 microglobulin, serum creatinine (SCr), uric acid,
      BUN, albumin; 24 h urinary levels of protein (Upro), albumin (Ualb) and
      creatinine were measured. The GFR was calculated according to Creatinine
      Clearance (CrCl), Cockcroft-Gault (CG) and Modification of Diet in Renal Disease
      (MDRD) formulas. The MDRD was used as the reference method. A GFR<80 mL/min/1.73
      m2 was considered as the lower cut-off limit. Mean levels of the serum parameters
      were found to be significantly higher in the patient group than they were in the
      control group (p<0.05). Mean CrCl, CG, and MDRD levels were lower in patients
      than they were in controls but the difference was statistically significant for
      CG and MDRD. The serum parameter having the best correlation with MDRD was SCr (r
      = -0.760) in patients and Cys C (r = -0.622) in controls. However, in ROC
      analysis; the area under curve (AUC) for Cys C was found to be superior (AUC =
      0.900) to the other markers. The CrCl was the parameter having the worst
      diagnostic efficiency (AUC = 0.598). As a conclusion, compared to other
      traditional markers, measurement of Cys C may be a better parameter to estimate
      GFR, especially to detect mild reductions of GFR in primary hypertensive
      patients.

PMID- 15957540
TI  - Invasive and innovative nephrology.
AB  - BACKGROUND: A nephrologist in the millennium offers comprehensive care to renal
      failure patients. Interventional nephrology plays a major role in this new
      approach. Overton Brooks Veterans Affairs Medical Center (OBVAMC) is the first
      federal health care provider in the nation offering such services. Lack of
      interventional radiologists and a busy surgical service has catalyzed the
      existence of interventional nephrology at this center. We report our early
      experience in successfully providing complete care to veterans with renal
      failure, despite multiple logistical obstacles. METHOD: The OBVAMC is an acute
      care facility providing nephrology support to hospitalized veterans and also
      handles access-related issues for eligible chronic dialysis patients. All
      procedures performed from June 2000 to September 2003 were analyzed. The
      procedures were performed in the cardiac catheterization laboratory or in the
      surgical operating rooms. RESULTS: A total of 366 procedures were performed,
      which included: 110 tunneled cuffed catheter (TCC) placements, 157 temporary dual
      lumen catheters, 36 TCC removals, 30 fistulograms, 24 thrombectomy-/angioplasty,
      1 stent placement, 3 Tenckhoff catheter placements, 3 central venograms, and 2
      accessory vein ligations. Bleeding from the exit site of a TCC in one patient was
      the only complication encountered. CONCLUSION: Interventional nephrology
      experience at OBVAMC has been very encouraging and has succeeded in providing
      optimal care to the veterans. Interventional nephrology programs can be developed
      in any tertiary care hospital.

PMID- 15957541
TI  - Fluvastatin in the treatment of dyslipidemia associated with chronic kidney
      failure and renal transplantation.
AB  - Premature atherosclerotic coronary heart disease driven by multiple risk factors
      is a major cause of morbidity and mortality among the 6 million patients in the
      United States with chronic renal failure. Consensus is that kidney failure and
      renal transplantation patients should be treated aggressively for dyslipidemia.
      Major medical literature databases were searched for published information about
      fluvastatin, a HMG-CoA reductase inhibitor, used in patients with impaired renal
      function. This article characterizes the dyslipidemia observed in these clinical
      settings and reviews the clinical experience with fluvastatin.

PMID- 15957542
TI  - Cellular immunity and levels of parathyroid hormone in uremic patients receiving
      hemodialysis.
AB  - OBJECTIVE: The clinical relevance of altered lymphocyte function and the possible
      relation with uremic toxins, such as parathyroid hormone (PTH) is not well
      understood. We studied the changes in cellular immunity in patients in
      hemodialysis (HD) therapy and examined the relationship between T-lymphocyte
      function and plasma levels of PTH. PATIENTS AND METHODS: Thirty-four patients (14
      male) were enrolled in this study (mean age: 63.20 +/- 10.01 years, M +/- SD, 12
      h/week HD). Our study population was divided into two groups: 18 patients with
      increased levels of PTH and 16 patients with normal levels of PTH. Lymphocyte
      subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD19+, CD3-/16+56+, CD4/CD8 ratio) were
      quantitated in both groups using monoclonal antibodies (Immunotech, Coulter) and
      flow cytometric analysis. Following analysis of variance (ANOVA) testing was
      performed to test differences between groups (SPSS version 10). RESULTS: A
      significant increase of CD2 was noticed in patients with increased levels of PTH
      (84.8 +/- 5.5 vs. 79.8 +/- 4, p<0.05). The CD3 population was also increased in
      patients with elevated PTH (72 +/- 8.6 vs. 68 +/- 9.2, p=NS). This group of
      patients had also significantly increased levels of CD3/8 (44.8 +/- 9.8 vs. 37.1
      +/- 5.8, p<0.05). The CD4/CD8 ratio levels were higher in patients with elevated
      PTH compared with those who had normal PTH (2.2 +/- 1.5 vs. 1.5 +/- 0.8, p=NS).
      CONCLUSIONS: The elevated level of PTH seems to affect the lymphocyte function
      and is associated with changes in cellular immunity in the hemodialysis
      population. Our study is in progress in order to enlarge our study population and
      collect more data, which will lead us to more solid conclusions.

PMID- 15957543
TI  - Comparative analysis of immunophenotypic abnormalities in cellular immunity of
      uremic patients undergoing either hemodialysis or continuous ambulatory
      peritoneal dialysis.
AB  - AIM: To investigate the abnormalities of cellular immune responses in patients on
      hemodialysis (HD) and in those on continuous ambulatory peritoneal dialysis
      (CAPD). PATIENTS AND METHODS: Forty-five (45) healthy volunteers, 34 patients on
      HD therapy, and 37 patients on CAPD were recruited for the present study.
      Lymphocyte subpopulations (CD2+, CD3+, CD3+/CD4+, CD3+/CD8+, CD3-/16+56+, CD19,
      and CD4/CD8) were determined by flow cytometry. RESULTS: Lymphopenia, decreased
      absolute counts, and altered percentage values of CD3+, CD3+/ 4+, and CD19+
      subpopulations were found in both patient groups. The HD and CAPD patients showed
      increased percentages of natural killer cells (CD3-/16+56+) compared to controls
      but CD4+/CD8+ ratio showed no significant changes among uremic patients and
      controls. CONCLUSIONS: Replacement therapy may contribute to the quantitative
      alterations of immune subsets found in HD and CAPD patients compared to normal
      subjects. We speculate that these changes account, at least in part, for the
      immune dysregulation observed in patients with chronic renal failure. Analysis of
      lymphocyte subsets will help the research and the evaluation of the possible
      causes of immunodeficiency in uremic patients undergoing replacement therapy and
      will probably contribute to more efficient and preventive strategies.

PMID- 15957544
TI  - Lymphocyte 5'-nucleotidase and aminopeptidase N activity in patients on
      maintenance hemodialysis treated with human recombinant erythropoietin and 1
      alpha-D3.
AB  - BACKGROUND: Patients with end-stage renal disease (ESKD) present an
      immunodeficiency state paradoxically exacerbated by hemodialysis (HD) and
      associated with signs of T-cell activation. B cells are also activated in uremia,
      and this activation could be altered by erythropoietin therapy in HD patients. In
      this study, the effects of human recombinant erythropoietin (rHu-EPO) and 1-alpha
      D3 treatments on lymphocyte immunomodulatory enzymes, aminopeptidase N (APN), and
      5'-nucleotidase activity in patients on HD were investigated in hemodialysis
      patients before and after two-month treatment with s.c. rHu-EPO (15 patients,
      2000-3000 U three times weekly) or oral 1-alpha-D3 (14 patients, 2 microg three
      times weekly). RESULTS: A two-month EPO treatment of 15 HD patients produced a
      rise in hemoglobin from 6.51 +/- 0.18 to 9.69 +/- 0.14 g/dL. Basal lymphocyte APN
      activity in HD patients was not significantly different from the level in healthy
      controls. Treatment of patients with rHu-EPO increased unstimulated lymphocyte
      APN activity to values significantly higher than those before treatment (p<0.05).
      A two-month pulse oral 1-alpha-D3 treatment of 14 HD patients increased
      hematocrit by 21% and raised hemoglobin from 7.11 +/- 0.32 to 8.80 +/- 0.39 g/dL.
      Unstimulated and Con A-stimulated lymphocyte APN activity after pulse oral 1
      alpha-D3 was significantly increased (p<0.01 and p<0.05, respectively) from the
      pretreatment levels. In HD patients lymphocyte basal, Con A-, and PMA-stimulated
      5'-nucleotidase activity was significantly higher (p<0.05) than it was in healthy
      controls. The two-month treatment with rHu-EPO or pulse oral 1-alpha D3 did not
      change the level of lymphocyte 5'-nucleotidase in these patients. CONCLUSIONS:
      This study demonstrated that a two-month treatment of HD patients with rHu-EPO or
      pulse oral 1-alpha D3 significantly increases activity of lymphocyte APN,
      important for cleavage of peptides and small proteins, which accumulate in the
      blood of ESKD patients. In HD patients lymphocyte ecto-5'-nucleotidase activity
      was significantly higher than that in healthy controls and was not changed after
      a two-month treatment with rHu-EPO or pulse oral 1-alpha D3. We speculate that
      oxidative stress activates 5'-nucleotidase and production of adenosine by
      lymphocytes of HD patients.

PMID- 15957545
TI  - Prediction of mortality in acute renal failure in the tropics.
AB  - Despite significant improvements in medical care, acute renal failure (ARF)
      remains a high risk for mortality. It is important to be able to predict the
      outcome in these patients in view of the emotional and ethical needs of the
      patients and to address questions of efficiency and quality of care. We analyzed
      the risk factors predicting mortality prospectively in a group of 265 patients
      using univariate and multiple logistic regression analysis. A prognostic model
      was evolved that included 10 variables. The model showed good discrimination
      [(receiver operating characteristic (ROC) area=0.91) and correctly classified
      88.30% of patients. The variables significantly associated with mortality were
      coma odds ratio (OR)=9.8], oliguria (OR=4.9), jaundice (OR=3.7), hypotension
      (OR=3.1), assisted ventilation (OR=2.3), hospital acquired ARF (OR=2.3), sepsis
      (OR=2.2), and hypoalbuminemia (OR=1.7). Age and male gender were included in the
      model as they are clinically important. The score was validated in the same
      sample by boot strapping. It was also validated in a prospective sample of 194
      patients. The model was calibrated by the Hosmer-Lemeshow goodness-of-fit test.
      It was compared with two generic illness scores and one specific ARF score and
      was found to be superior to them. The model was verified in different subgroups
      of ARF like hospital acquired, community acquired, intensive care settings,
      nonintensive care settings, due to sepsis, due to nonsepsis etiologies, and
      showed good predictability and discrimination.

PMID- 15957546
TI  - Statin therapy helps to control blood pressure levels in hypertensive
      dyslipidemic patients.
AB  - AIM: Aside from lowering lipid levels; statins improve endothelial function,
      decrease platelet aggregation, reduce procoagulant blood factors, and decrease
      vascular tone. This study was conducted to investigate the possible effect of
      atorvastatin on blood pressure (BP) in a group of hypertensive and dyslipidemic
      patients. METHODS: Thirty-six hypertensive and dyslipidemic patients with
      inadequately controlled lipid levels by diet were treated with atorvastatin 20
      mg/day for 8 weeks and compared with 24-patient matched controls treated with
      diet alone. The type and dosage of antihypertensive medications were not altered
      during statin therapy. Blood lipid profile including total cholesterol (TC), low
      density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG)
      levels were noted at inclusion and after 8 weeks. Ambulatory BP monitoring (ABPM)
      was carried out at study entry and at the end of week eight. RESULTS: A total of
      49 patients (32 patients in the atorvastatin group and 17 patients in the control
      group) completed the 3-month follow-up period of observation. The ABPM studies
      indicated significant reductions in total average systolic BP, total average
      diastolic BP, total average mean BP, day average systolic BP, day average
      diastolic BP, night average systolic BP, night average diastolic BP, and night
      average mean BP levels in the atorvastatin group, whereas these reductions were
      not observed in the control group. CONCLUSION: Our results indicate that
      atorvastatin therapy significantly improves BP control in hyperlipidemic
      hypertensive patients. However, the effects of other statins on BP, as well as,
      the different dosages need to be further investigated.

PMID- 15957547
TI  - Long-term impact of chronic hemodialysis on glycemic control and serum lipids in
      insulin-treated type 2-diabetic patients.
AB  - There are only a few data in the literature concerning metabolic control in
      insulin-treated diabetic patients with end stage renal disease (ESRD). The aim of
      the study was to find out the long-term impact of hemodialysis on glycemic
      control and lipid values in type 2 diabetic patients. Twenty insulin-treated type
      2 diabetic patients (age 62 +/- 9 years, f:m=6:14) were evaluated. We compared
      HbAlc, fasting blood glucose (FBG), body weight, serum lipids, insulin
      requirement, and blood-pressure (BP) 12 and 6 months before dialysis, at the
      start of dialysis, and 6 as well as 12 months after the start. RESULTS: The mean
      HbA1c- and FBG-values were not significantly different before and after the start
      of dialysis therapy. The average insulin requirement was 26 +/- 10 IU/day in the
      predialysis period, 25 +/- 12 IU/day at the start, and 24 +/- 13 as well as 22 +/
      13 IU/day after the start of dialysis. The mean cholesterol level fell
      significantly from 199 +/- 63 and 190 +/- 49 mg/dL in the predialysis phase to
      167 +/- 62 and 157 +/- 38 mg/dL after dialysis began. The triglyceride
      concentrations decreased only slightly after the start of dialysis. The incidence
      of hypoglycemia (n/patient/month) was markedly lower in the predialysis phase
      (0.4 vs. 0.6, NS) than after start of dialysis. In patients with residual
      diuresis (<500 mL urine/day) the needed insulin doses decreased significantly by
      29% compared to patients with higher residual diuresis, whose insulin requirement
      remained unchanged. In summary, hemodialysis had no significant long-term effect
      on glycemic control in insulin-treated type 2 diabetic patients, but incidence of
      hypoglycemia tended to be higher under hemodialysis than in the predialysis
      period. Lipid levels tended to be lower after the initiation of dialysis therapy.
      Insulin requirement under hemodialysis decreased only in patients with loss of
      residual urine volume (below 500 mL urine/day).

PMID- 15957548
TI  - Favorable graft survival in renal transplant recipients with polycystic kidney
      disease.
AB  - Graft survival in the autosomal dominant polycystic kidney disease (ADPKD)
      transplant population at our center was compared to other end stage renal disease
      (ESRD) transplant recipients (excluding diabetics). There were 1512 adult
      cadaveric renal transplants carried out at our center between 1989 and 2002.
      After exclusions, 1372 renal grafts were included in the study. Using Kaplan
      Meier methods, patient and graft survival were determined and compared between
      the two groups. Mean age at transplant was significantly older for the ADPKD
      group of patients. The age adjusted graft survival at 5 years was 79% for ADPKD
      patients compared to 68% in the controls. Patient survival for ADPKD patients
      improved from 89% at 5 years to 95% when age adjusted. Using the Cox proportional
      hazards models to compare ADPKD with other causes of ESRD (including recipient
      age and other variables) in a multifactorial model, ADPKD was significant at the
      5% level (p=0.036). This study demonstrates a graft and patient survival
      advantage in ADPKD patients when age-matched compared to other ESRD patients.

PMID- 15957549
TI  - Hemodialysis procedure does not affect the levels of sICAM-1 and sVCAM-1 in
      patients with end stage renal disease.
AB  - Atherosclerosis is by far the leading cause of mortality and morbidity in
      patients with end stage renal disease undergoing chronic hemodialysis (HD).
      Vascular endothelial cell adhesion molecules like the intercellular adhesion
      molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are
      involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1,
      sVCAM-1) are considered potential serum markers of endothelial activation and
      atherosclerosis. The aim of this study was to clarify the influence of the HD
      procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal
      disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean
      age 61 +/- 12) on chronic HD treatment. Diabetes mellitus coexisted in eight
      patients and arterial hypertension in 23 patients. Blood was drawn before, every
      hour during, and after a single HD session in each patient. Low-flux cuprophane
      dialyzers (GFS 12, Gambro, Lund, Sweden) were used in 22 and high-flux
      polysulfone dialyzers (Hemoflow F 60S, Fresenius, Oberursel, Germany) in 13
      cases. At 30 min into the HD session (n=31, 20 low-flux HD, 11 high-flux HD)
      blood was drawn simultaneously from the entrance and the exit line of the
      dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1
      were determined by commercially available enzyme immunoassays (ELISA, R&D
      Systems, Minneapolis, USA). Results were corrected according to
      hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in
      patients with end stage renal disease before the beginning of the dialysis
      session when compared to healthy controls (1449 +/- 497 ng/mL vs. 691 +/- 118
      ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1
      (231 +/- 58.5 ng/mL vs. 236.4 +/- 96.8 ng/mL in healthy controls). These levels
      remained stable in all measurements throughout the dialysis procedure.
      Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the
      passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by
      the existence of diabetes mellitus, hypertension, or by the utilization of
      biocompatible, high flux dialyzers. Our study confirms that in chronic HD
      patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules
      are not affected by the HD procedure. These findings probably can be attributed
      to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the
      different sources of the two molecules. Neither coexisting diabetes mellitus nor
      arterial hypertension influences the circulating levels of these adhesion
      molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal
      contribution to their metabolism, and their role as markers of atherosclerosis in
      chronic renal disease need further evaluation.

PMID- 15957550
TI  - Enhanced urinary adiponectin excretion in IgA-nephropathy patients with
      proteinuria.
AB  - Adiponectin is secreted specifically by adipose tissue. It was reported that the
      serum adiponectin level was markedly increased in patients with end-stage renal
      disease and was positively associated with abnormal renal function in type 2
      diabetes. Recently, we found that urinary adiponectin level was significantly
      increased in type 2 diabetic patients with overt diabetic nephropathy, but not in
      those without nephropathy. The aim of the present study was to evaluate whether
      the urinary adiponectin level is increased not only in diabetic patients with
      macroalbuminuria but also in IgA-nephropathy patients with macroalbuminuria. We
      measured urinary adiponectin levels in 24 healthy control subjects, 12 IgA
      nephropathy patients, and 19 type 2 diabetic nephropathy patients, and they were,
      in medians, 2.24 microg/g creatinine (ranges of 0.85 to approximately 3.70), 59.2
      microg/g creatinine (4.95 to approximately 186), and 33.1 microg/g creatinine
      (4.69 to approximately 114), respectively. In the two patient groups, urinary
      adiponectin levels were significantly higher than in control subjects (P<0.01).
      Moreover, positive correlations between urinary adiponectin levels and albumin-to
      creatinine ratios were observed in IgA-nephropathy (R2=0.53, P<0.01) and diabetic
      nephropathy patients (R2=0.61, P<0.01), but not in control subjects. Serum
      adiponectin levels were unchanged in these three groups. These findings suggested
      that the increase of urinary adiponectin levels partly results from enhanced
      filtration of circulating adiponectin through the changes of glomerular
      permselectivity and intraglomerular hydruric pressure. However, clinical
      implication of urinary adiponectin excretion in healthy control remains to be
      elucidated.

PMID- 15957551
TI  - Nephrotoxicity related to new therapeutic compounds.
AB  - Toxic nephropathy is an important cause of reversible renal injury. This article
      focuses on the nephrotoxicity of several new therapeutic compounds. Selective
      cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension,
      ankle edema, and acute renal failure. The incidence of renal complication is
      similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates,
      especially when used in high dose for prolonged duration, can cause toxic acute
      tubular necrosis and renal failure. Pamidronate is also associated with a
      specific form of collapsing focal segmental glomerulosclerosis similar to one
      found in patients with human immunodeficiency virus (HIV) infection. Acyclic
      nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like
      syndrome and progressive renal impairment. On the other hand, indinavir, a potent
      protease inhibitor for the treatment of HIV infection, can cause crystalluria,
      renal stone, acute tubular obstruction and chronic interstitial nephritis.
      Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are
      associated with acute renal failure with characteristic renal histology known as
      osmotic nephrosis. In short, physicians should be cautious about possible renal
      toxicity during the use of any new therapeutic agents.

PMID- 15957552
TI  - Diltiazem attenuates oxidative stress in diabetic rats.
AB  - Diabetic nephropathy is the main cause of end stage renal damage. Oxidative
      stress is involved in the etiology of diabetic nephropathy and intracellular
      calcium is reported to play a considerable role in the development of renal
      damage in the diabetic kidney. Calcium antagonism can slow the progression of
      renal impairment in diabetes. The present study was thus designed to examine the
      effect of a nondihydropyridine calcium channel blocker, diltiazem, on renal
      function, oxidative stress, and nitric oxide (NO) release 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, the rats were divided
      in to four groups: control rats, diabetic rats treated with saline, and two
      groups of diabetic rats treated with diltiazem (5 and 10 mg/kg, i.p,
      respectively) for 8 weeks starting from 4 weeks after STZ injection. Renal
      function was assessed by creatinine, blood urea nitrogen, creatinine clearance,
      and urea clearance. Oxidative stress was measured by renal malondialdehyde (MDA),
      reduced glutathione (GSH), superoxide dismutase (SOD), and catalase. We also
      measured renal nitrite levels. At the end of the 8 weeks, diabetic rats exhibited
      renal dysfunction as evidenced by reduced creatinine and urea clearance along
      with enhanced albumin excretion rate as compared with control rats. Biochemical
      analysis of kidneys revealed a marked increase in oxidative stress demonstrated
      by increased lipid peroxidation and decreased activities of key antioxidant
      enzymes, GSH, SOD, and catalase in diabetic rats. Release of NO also
      significantly higher in diabetic rats than controls. Chronic treatment with
      diltiazem in diabetic rats significantly attenuated both renal dysfunction and
      oxidative stress along with increased NO levels as compared with untreated
      diabetic rats. The kidneys of diabetic rats showed morphological changes such as
      hyaline casts, glomerular thickening, and moderate interstitial fibrosis and
      arteriolopathy, whereas diltiazem administration markedly prevented diabetic
      induced renal morphological alterations. The present study suggests that
      oxidative stress/nitrosative stress is increased in the diabetic kidney and
      calcium channel blockage can prevent these changes. The results also suggest that
      in STZ-induced diabetic rats, the protective action of diltiazem might be
      mediated, at least in part, by its effect on tissue oxidant/antioxidant status.

PMID- 15957553
TI  - Evaluation of oxidative stress after repeated intravenous iron supplementation.
AB  - Parenteral iron has been recommended for the treatment of iron deficiency in the
      majority of maintenance hemodialyzed (HD) patients. However, iron supplementation
      and consequent over saturation of transferrin and high iron levels, may aggravate
      oxidative stress already present in these patients. This study aimed to further
      clarify the role of repeated intravenous iron therapy as a supplementary cause of
      oxidative stress in HD patients. Markers of free radical activities (carbonyl
      reactive derivatives, CRD, thiol groups, SH, malondialdehyde, MDA) and
      antioxidant enzyme activities (superoxide dismutase, SOD and glutathione
      peroxidase, GPX) were determined in plasma and red blood cells (RBC) of 19
      hemodialysis patients given a total iron dose of 625 mg (ferrogluconat,
      Ferrlecit, 62.5 mg). Blood samples were taken before the first and after the last
      dose of iron. Twenty apparently normal subjects served as healthy controls.
      Before iron treatment, HD patients exhibited increased concentrations of MDA and
      CRD in plasma and red blood cells, accompanied with impaired antioxidant
      capacity. All patients responded to iron therapy with a significant increase in
      their serum ferritin, serum iron, hemoglobin, and red blood cells levels.
      However, iron treatment resulted in enhanced oxidative stress in plasma of HD
      patients, since significant increase in plasma MDA and CRD concentrations,
      together with a decrease in nonprotein SH groups levels were detected.
      Supplementation with iron did not significantly influence plasma SOD and GPX
      activities, nor did any of the red blood cell parameters tested. Our data show
      that, despite improvement in hematological parameters, an increase in iron stores
      due to supplementation could also contribute to increased free radical production
      in HD patients.

PMID- 15957554
TI  - Focal segmental glomerulosclerosis associating Kimura disease.
AB  - Kimura disease presents as a benign subcutaneous mass. Although it principally
      affects the skin and soft tissues, there is a high prevalence of related renal
      disease. We report a case of Kimura disease from western Asia, presenting itself
      as nephrotic syndrome, and this case was seen at a nontransplant kidney
      presenting with focal segmental glomerulonephritis.

PMID- 15957555
TI  - Peer influence in children and adolescents: crossing the bridge from
      developmental to intervention science.
AB  - Considerable evidence supports the hypothesis that peer relationships influence
      the growth of problem behavior in youth. Developmental research consistently
      documents the high levels of covariation between peer and youth deviance, even
      controlling for selection effects. Ironically, the most common public
      interventions for deviant youth involve segregation from mainstream peers and
      aggregation into settings with other deviant youth. Developmental research on
      peer influence suggests that desired positive effects of group interventions in
      education, mental health, juvenile justice, and community programming may be
      offset by deviant peer influences in these settings. Given the public health
      policy issues raised by these findings, there is a need to better understand the
      conditions under which these peer contagion effects are most pronounced with
      respect to intervention foci and context, the child's developmental level, and
      specific strategies for managing youth behavior in groups.

PMID- 15957556
TI  - Exposure to externalizing peers in early childhood: homophily and peer contagion
      processes.
AB  - Guided by a transactional model, we examined the predictors and effects of
      exposure to externalizing peers in a low-risk sample of preschoolers and
      kindergarteners. On the basis of daily observations of peer interactions, we
      calculated measures of total exposure to externalizing peers and measures of
      exposure to same- and other-sex externalizing peers. Analyses of predictors of
      externalizing peer exposure supported a homophily hypothesis for girls. Tests of
      peer contagion effects varied by sex, and exposure to externalizing peers
      predicted multiple problem behaviors for girls but not for boys. Sex differences
      were a function of children's own sex, but not of peers' sex. The study provides
      evidence of externalizing peer exposure effects in a low-risk sample of young
      children, notably for girls.

PMID- 15957557
TI  - A model of contagion through competition in the aggressive behaviors of
      elementary school students.
AB  - This article extends the work of Kellam, Ling, Merisca, Brown and Ialongo (1998)
      by applying a mathematical model of competition between children to peer
      contagion in the aggressive behaviors of elementary school students. Nonlinearity
      in the relationship between group aggression and individual aggression at 2-year
      follow-up is present. Consistent with the findings of Kellam et al. (1998),
      hierarchical linear modeling indicates that the relationship is statistically
      significant for those students whose initial parental ratings of aggressive
      behavior were above the sample median. In the context of competition between
      students, the behavior of initially aggressive students may be negatively
      reinforced. Lowering aggression in the school environment may therefore be the
      most effective way to lower the level of these students' aggressive behavior.

PMID- 15957558
TI  - False consensus and adolescent peer contagion: examining discrepancies between
      perceptions and actual reported levels of friends' deviant and health risk
      behaviors.
AB  - Adolescents' perceptions of their friends' behavior strongly predict adolescents'
      own behavior, however, these perceptions often are erroneous. This study examined
      correlates of discrepancies between adolescents' perceptions and friends' reports
      of behavior. A total of 120 11th-grade adolescents provided data regarding their
      engagement in deviant and health risk behaviors, as well as their perceptions of
      the behavior of their best friend, as identified through sociometric assessment.
      Data from friends' own report were used to calculate discrepancy measures of
      adolescents' overestimations and estimation errors (absolute value of
      discrepancies) of friends' behavior. Adolescents also completed a measure of
      friendship quality, and a sociometric assessment yielding measures of peer
      acceptance/rejection and aggression. Findings revealed that adolescents' peer
      rejection and aggression were associated with greater overestimations of friends'
      behavior. This effect was partially mediated by adolescents' own behavior,
      consistent with a false consensus effect. Low levels of positive friendship
      quality were significantly associated with estimation errors, but not
      overestimations specifically.

PMID- 15957559
TI  - The impact of first-grade "friendship group" experiences on child social outcomes
      in the fast track program.
AB  - Many interventions for children's behavior problems successfully utilize a group
      format for social skills training, providing opportunities for practice and
      performance feedback from peers. Recent studies however, suggest that grouping
      aggressive children together may reduce intervention effectiveness or even
      increase risk. The present study examined the relative impact of children's own
      behavior and their experiences with peers in the first-grade "friendship groups"
      of Fast Track, a multi-component preventive intervention program. Two-hundred
      sixty-six children (56% minority, 29% female) participated in 55 friendship
      groups. Children's own positive and negative behavior in friendship groups was
      related to relative improvements in social cognitive skills, prosocial behavior,
      and aggression, assessed through child interviews, teacher ratings, and peer
      sociometric nominations. Results from hierarchical linear models also revealed
      that the amount of peer escalation children received for their disruptive
      behavior during sessions impeded some intervention gains, whereas mere exposure
      to other children's positive or negative behavior was rarely related to outcomes.

PMID- 15957560
TI  - Proximal peer-level effects of a small-group selected prevention on aggression in
      elementary school children: an investigation of the peer contagion hypothesis.
AB  - Examined peer contagion in small group, selected prevention programming over one
      school year. Participants were boys and girls in grades 3 (46 groups, 285
      students) and 6 (36 groups, 219 students) attending school in low-resource, inner
      city communities or moderate resource urban communities. Three-level hierarchical
      linear modeling (observations within individuals within groups) indicated that
      individual change in aggression over time related to the average aggression of
      others in the intervention group. The individual child was "pulled" toward peers'
      mean level of aggression; so the intervention appeared to reduce aggression for
      those high on aggression, and to make those low on aggression more aggressive.
      Effects appeared to be magnified in either direction when the child was more
      discrepant from his or her peers. From these results we derive a principle of
      "discrepancy-proportional peer-influence" for small group intervention, and
      discuss the implications of this for aggregating aggressive children in small
      group programs.

PMID- 15957561
TI  - Association with delinquent peers: intervention effects for youth in the juvenile
      justice system.
AB  - Although association with delinquent peers is a recognized precursor to ongoing
      delinquency problems, youth in the juvenile justice system are commonly
      prescribed intervention services that aggregate delinquent youth. However, little
      is known about the process variables that mediate the relationship between
      aggregating youth in intervention settings and poor subsequent outcomes. We
      examined data from two randomized intervention trials (one male sample and one
      female sample) with delinquent adolescents placed either in Multidimensional
      Treatment Foster Care (MTFC) or in group care. Path analyses suggested that the
      MTFC youth had fewer associations with delinquent peers at 12 months than did the
      group care youth. Further, associating with delinquent peers during the course of
      the intervention mediated the relationship between group condition and 12-month
      delinquent peer association. Implications for the development of interventions
      with delinquent youth are discussed.

PMID- 15957562
TI  - Intervention groups for adolescents with conduct problems: is aggregation harmful
      or helpful?
AB  - Past research has suggested that the aggregation of deviant peers during
      treatment may cause harmful effects (T. J. Dishion, J. McCord, & F. Poulin,
      1999). This study compared the effectiveness of problem-solving skills training
      groups in which all members had conduct problems ("pure" group condition) with
      groups that consisted of adolescents with and without behavior problems ("mixed"
      group condition). Participants were 139 sixth- and seventh-graders (mean age =
      12.7; 63% male; 55% White) enrolled at public middle schools. Pre-, post-, and 6
      month follow-up data were collected, along with intervention process variables.
      Results showed that, contrary to the deviancy training hypothesis, adolescents in
      the pure-group condition engaged in more adaptive in-session behavior and
      received lower scores on the parent and teacher ratings of externalizing behavior
      at postintervention than those in the mixed-group condition. Mediation analyses
      showed that the deviancy training that occurred in the mixed-group condition
      accounted for their worse postintervention scores, findings consistent with the
      deviancy training hypothesis.

PMID- 15957563
TI  - Evaluation of a high school peer group intervention for at-risk youth.
AB  - The purpose of this paper is to examine the effectiveness of Reconnecting Youth,
      a prevention program for at-risk high school youth. Data are from a large,
      independently evaluated effectiveness trial in two diverse urban school
      districts. A total of 1,218 students participated; 50% were male; average age was
      15. We tested whether positive efficacy trial effects could be replicated, and
      whether any negative behavioral effects occur when clustering high-risk youth.
      Although mixed program effects were observed at immediate post-intervention, only
      negative effects were found at 6-month follow-up. These effects included less
      optimal scores on measures of GPA, Anger, School Connectedness, Conventional Peer
      Bonding, and Peer High-Risk Behaviors. Overall, we found little support for the
      use of this social-influence--model intervention aimed at increasing school
      connectedness for high-risk youth. Further, this study provides evidence that
      clustering high-risk youth in preventive interventions has the potential for
      iatrogenic effects.

PMID- 15957564
TI  - Peer effects in drug use and sex among college students.
AB  - Past research suggests that congregating delinquent youth increases their
      likelihood of problem behavior. We test for analogous peer effects in the drug
      use and sexual behavior of male (n = 279) and female (n = 435) college students,
      using data on the characteristics of first-year roommates to whom they were
      randomly assigned. We find that males who reported binge drinking in high school
      drink much more in college if assigned a roommate who also binge drank in high
      school than if assigned a nonbinge-drinking roommate. No such multiplier effect
      is observed for females, nor are multiplier effects observed for marijuana use or
      sexual behavior for either males or females. Students who did not engage in these
      behaviors in high school do not appear to be affected by their roommates' high
      school behavior.

PMID- 15957565
TI  - Peer interaction: what causes what?
AB  - Peer interaction is examined as a source of behavior change in children and
      adolescents. The dynamics of peer influence are discussed in terms of six issues:
      characteristics of the influence source; characteristics of the child or
      adolescent being influenced; the relationship existing between influence source
      and the individual being influenced; developmental change; processes underlying
      peer influence; and constraints deriving from the behavior domain being examined.
      Research shows that contact with peers has complex effects on individual
      behavior, and numerous moderators and mediators must be considered in order to
      account for them. The discussion is linked to the papers included in this special
      issue.

PMID- 15957566
TI  - Peer contagion in interventions for children and adolescents: moving towards an
      understanding of the ecology and dynamics of change.
AB  - The influence of deviant peers on youth behavior is of growing concern, both in
      naturally occurring peer interactions and in interventions that might
      inadvertently exacerbate deviant development. The focus of this special issue is
      on understanding the moderating and mediating variables that account for peer
      contagion effects in interventions for youth. This set of nine innovative papers
      moves the field forward on three fronts: (1) Broadening the empirical basis for
      understanding the conditions under which peer contagion is more or less likely
      (that is, moderators of effects); (2) Identifying mechanisms that might account
      for peer contagion effects (mediators); and (3) Forging the methodological rigor
      that is needed to study peer contagion effects within the context of intervention
      trials. We propose an ecological framework for disentangling the effects of
      individuals, group interactions, and program contexts in understanding peer
      contagion effects. Finally, we suggest methodological enhancements to study peer
      contagion in intervention trials.

PMID- 15957567
TI  - Modeling pathways to affective barriers on colorectal cancer screening among
      Japanese Americans.
AB  - The study aimed to identify the mechanisms through which colorectal cancer (CRC)
      specific affective barriers, including fear of finding CRC, embarrassment, and
      concerns for screening discomfort, can be reduced to guide the development of
      interventions aimed at the secondary prevention of CRC. A model explaining these
      affective barriers was developed and tested among a random sample of 305
      asymptomatic Japanese Americans using a path analysis. The model suggested that
      affective barriers could be reduced by increasing CRC-related knowledge, which
      could be enhanced by acculturation, social support, and physician recommendation.
      Interventions that focus on increasing CRC-related knowledge could reduce
      affective barriers to CRC screening for this population when taking the
      enhancement of communication skills and interpersonal interactions into account.

PMID- 15957568
TI  - Correlates of colorectal cancer screening compliance among urban Hispanics.
AB  - Colorectal cancer (CRC) is the second most common cancer among Latinos; screening
      can reduce mortality from CRC. The aims of this study are; to assess the current
      compliance with free colorectal cancer screening among Hispanic women who are
      participating in a national breast and cervical cancer screening program
      (NBCCEDP), and to examine the effects of a set of key constructs from the HBM and
      the TPB on compliance with the Fecal Occult Blood Test (FOBT). We consecutively
      recruited 950 women from among those attending an initial appointment at an
      NBCCEDP site in northern Manhattan, and administered a questionnaire. Patients
      were offered a free Hemoccult kit, alongside instructions and print materials.
      The rate of FOBT compliance (in kit return) was 77.3%. Fatalism remained a
      statistically significant influence on FOBT compliance in the multivariate
      models, and there was a trend for higher FOBT return among West Indies women
      (primarily from the Dominican Republic). The findings of this study demonstrate
      the feasibility and acceptability of distributing FOBT kits through an existing
      national program for cancer screening of women. The results justify replication
      in a more heterogeneous group of Hispanics, with longer-term followup.

PMID- 15957569
TI  - Medication compliance during a smoking cessation clinical trial: a brief
      intervention using MEMS feedback.
AB  - This study examined the role of a Medication Event Monitoring System (MEMS) to
      assess pill-taking behavior and enhance compliance within a randomized trial of
      bupropion-SR for smoking cessation. Female participants (N = 97) received MEMS
      bottles containing bupropion-SR 150 mg or placebo, to be taken twice daily. A
      randomly selected "feedback" group of participants was told about the recording
      device in the bottle cap and received weekly graphic feedback showing their pill
      taking behavior with specific instructions for improving compliance. A "no
      feedback" group was not informed about the MEMS bottles, and did not receive
      further instruction or feedback beyond the standard dosing instructions.
      Compliance outcomes were the total doses taken and number of doses taken within
      the prescribed time interval. Results indicated significantly higher compliance
      over time for the feedback group. Participation in the feedback group predicted
      higher compliance beyond demographic, smoking, and health belief variables,
      suggesting significant benefit in providing brief feedback and instruction
      throughout the medication regimen.

PMID- 15957570
TI  - Suicidal ideation and attempted suicide among women living with HIV/AIDS.
AB  - The prevalence, timing, and predictors of suicidal ideation and attempted suicide
      were evaluated in a sample of 207 HIV-positive women in New York City. Twenty-six
      percent of the women reported attempting suicide since their HIV diagnosis. Of
      those who made an attempt, 42% acted within the first month after diagnosis and
      27% acted within the first week. AIDS diagnosis, psychiatric symptoms, and
      physical or sexual abuse were significant positive predictors of both suicidal
      ideation and attempts. Contrary to expectations, having children and being
      employed were also significant positive predictors. Spirituality was
      significantly negatively associated with suicidal ideation only. These results
      suggest that suicide prevention measures should be implemented for HIV-positive
      women immediately after diagnosis. Specifically, interventions should target
      those with an AIDS diagnosis, psychiatric symptoms, an abuse history, children,
      or employment. The encouragement of spiritual connection seems to be a deterrent
      to suicidal thoughts and is a possible avenue for intervention.

PMID- 15957571
TI  - The unique effects of forgiveness on health: an exploration of pathways.
AB  - The relationship of forgiveness, both state and trait, to health was assessed.
      Eighty-one community adults completed a packet of questionnaires and participated
      in a laboratory interview about a time of hurt or betrayal. Heart rate and blood
      pressure were recorded during a 10 min baseline, the interview and during a
      recovery period; interviews were structured around a framework of questions and
      videotaped. Four measures of forgiveness were all statistically associated with
      five measures of health (physical symptoms, medications used, sleep quality,
      fatigue, and somatic complaints). Trait forgiveness was associated with decreased
      reactivity (rate-pressure product) to the interview, but sympathetic reactivity
      did not account for the trait forgiveness-health association. Four mechanisms or
      pathways by which forgiveness could lead to fewer physical symptoms were
      examined: spirituality, social skills, reduction in negative affect, and
      reduction in stress. All factors either partially or fully mediated the effect of
      forgiveness on health; however, the strongest mediator for both state and trait
      forgiveness was reduction in negative affect. For state forgiveness, the second
      strongest mediator was reduction in stress; for trait forgiveness, both conflict
      management and reduction in stress were strong contributors.

PMID- 15957572
TI  - Reliability and construct validity of the pain distress inventory.
AB  - We conducted three studies to evaluate further the reliability and construct
      validity of a new self-report instrument, the Pain Distress Inventory (PDI; Osman
      et al., 2003, The Pain Distress Inventory: Development and initial psychometric
      properties, J. Clin. Psychol. 59: 767-785). In Study I, exploratory and
      confirmatory factor analytic results confirmed the replicability of the four
      factor oblique solution of the PDI in a mixed sample of students and nonstudents.
      We also found strong evidence for criterion-related validity of scores on this
      instrument. In Study II, multisample analyses results found further evidence for
      equivalence of structure of the PDI across African American and Caucasian young
      adults. Ethnic and gender group differences were obtained on two of the PDI scale
      scores. Internal consistency reliability estimates on the PDI total and scale
      scores were good in both Studies I and II. In Study III, additional analyses of
      internal consistency and known-groups validity established strong support for
      construct validity of the PDI.

PMID- 15957573
TI  - Predicting emotional response to unsuccessful fertility treatment: a prospective
      study.
AB  - The predictive value of a comprehensive model with personality characteristics,
      stressor related cognitions, coping and social support was tested in a sample of
      187 nonpregnant women. The emotional response to the unsuccessful treatment was
      predicted out of vulnerability factors assessed before the start of the
      treatment. The results indicated the importance of neuroticism as a vulnerability
      factor in emotional response to a severe stressor. They also underlined the
      importance of helplessness and marital dissatisfaction as additional risk
      factors, and acceptance and perceived social support as additional protective
      factors, in the development of anxiety and depression after a failed fertility
      treatment. From clinical point of view, these results suggest fertility-related
      cognitions and social support should receive attention when counselling women
      undergoing IVF or ICSI treatment.

PMID- 15957574
TI  - Acculturation and its relationship to smoking and breast self-examination
      frequency in African American women.
AB  - The concept of acculturation has been used to understand differences in health
      behaviors between and within a variety of racial and ethnic immigrant groups. Few
      studies, however, have examined the potential impact of acculturation on health
      behaviors among African Americans. The present study has two goals: 1) to
      reconfirm relations between acculturation and cigarette smoking; 2) to
      investigate the impact of acculturation on another type of health behavior,
      cancer screening and specifically breast self-examination (BSE). African American
      women (N = 66) attending an inner-city cancer-screening clinic completed study
      questionnaires. Results reconfirmed psychometric properties of the African
      American Acculturation Scale (AAAS); replicated the negative association between
      acculturation and lifetime smoking status; and found relations between
      acculturation and women's adherence to BSE frequency guidelines. Findings from
      this study raise the possibility that specific aspects of acculturation may
      better explain specific health behaviors.

PMID- 15957575
TI  - Do new drivers equal new donors? An examination of factors influencing organ
      donation attitudes and behaviors in adolescents.
AB  - Adolescent and parent organ donation attitudes, knowledge, communications, and
      donor card signing rates were assessed. Parent-adolescent dyads (N = 137) were
      recruited at a Department of Motor Vehicles (DMV). Using discriminant analysis,
      attitude, knowledge, and communication variables adequately classified adolescent
      donor status. Overall, adolescent positive attitude toward donation was the most
      powerful variable discriminating between donors and nondonors. Examining only
      participants who had discussed donation with parents, the nature of parent
      adolescent discussions about organ donation became the most important variable in
      donor classification. Adolescent donors reported significantly more positive and
      less negative attitudes, had parents with more positive and less negative
      attitudes, and had engaged in more frequent and more positive communications with
      parents about organ donation.

PMID- 15957576
TI  - The aging hippocampus: navigating between rat and human experiments.
AB  - Aging is associated with impairments in certain aspects of cognition, especially
      learning and memory. The hippocampus is a structure intimately involved with
      certain aspects of learning and memory, and is especially vulnerable to the
      course of aging. Recent findings, primarily from cognitive, magnetic resonance
      imaging, and magnetic resonance spectroscopy studies, but also briefly physiology
      and neurogenesis work, are reviewed. Evidence suggests that age-related
      impairment of hippocampus-dependent cognition is associated with changes on
      various levels of investigation in both humans and non-human animals. Also, the
      emphasis is placed on tasks and techniques that can be used to test both non
      human and human animals in an attempt to bridge the gulf between the vast bodies
      of knowledge about the hippocampus in different species. To the extent that
      changes with normal aging are understood, they may aid in diagnosis, prevention,
      and/or treatment of age-related learning and memory deficits in both normal and
      pathological aging. In addition, studies of the aging hippocampus may have a side
      effect in leading to a better understanding of the mechanisms that underlie
      learning and memory in general.

PMID- 15957577
TI  - Drosophila as a novel animal model for studying the genetics of age-related
      memory impairment.
AB  - Understanding the molecular mechanisms underlying age-related memory impairment
      (AMI) is important not only from a scientific viewpoint but also for the
      development of therapeutics that may eventually lead to the development of drugs
      to combat memory loss. AMI has been generally considered to be an overall or
      nonspecific decay of memory processes that results from dysfunction of neural
      networks. However, behavioral genetics to test this hypothesis have not been
      performed previously, due, in part, to the long lifespan of animal models. Using
      Drosophila, the first extensive behavioral-genetic characterization of AMI has
      been carried out. In Drosophila, memory acquired after a single olfactory
      conditioning paradigm has three distinct phases: short-term memory (STM), middle
      term memory (MTM), and longer-lasting anesthesia-resistant memory (ARM).
      Significantly, AMI results from the specific decay of only one memory component,
      amnesiac-dependent MTM, and not other components. Since amnesiac encodes peptides
      that enhance adenylyl cyclase activity, these studies suggest the importance of
      the cAMP signaling pathway in AMI in Drosophila, a finding consistent with
      several models of AMI in mammals. Although many advances have been made in the
      study of pathways involved in aging, much remains to be elucidated on how these
      pathways affect memory formation to cause AMI. Due to its short lifespan,
      powerful genetics, and well-characterized and conserved pathways involved in
      memory and lifespan, Drosophila will be a useful model system for studying the
      molecular mechanisms underlying this process.

PMID- 15957578
TI  - Human functional neuroimaging connectivity research in dependence.
AB  - Functional and effective connectivity are relatively new techniques in the
      analysis of functional neuroimaging studies in humans. They have previously been
      used in studies of 'normal' psychological and neurological processes such as
      vision before gradually transferring into use in pathological disease states such
      as schizophrenia. These techniques are now beginning to extend into the field of
      substance misuse and dependence. So far, most functional neuroimaging studies in
      this field have shown consistent patterns of activation in several brain regions,
      and theories are emerging based upon these and animal models. Studies of brain
      connectivity can now begin to help further unravel the tangle of disparate brain
      regions and their connections that underpin the psychopharmacological processes
      of dependence.

PMID- 15957579
TI  - The other transmissible spongiform encephalopathies.
AB  - Murine leukemia viruses may produce encephalopathies that have the same
      characteristics as those induced by infectious proteins or prions: neuronal loss,
      astrocytosis, and absence of inflammatory response. The pathogenic mechanism is
      still poorly understood but it seems that it involves the envelope proteins
      (Env), which may be misprocessed in the cell, giving rise to pathogenic isoforms
      that trigger oxidative damage. Env may also affect the cytokine pattern in the
      central nervous system and thus, induce encephalopathy.

PMID- 15957580
TI  - Expert evidence law reform.

PMID- 15957581
TI  - Jurisprudential legerdemain: damages for gratuitous services and attendant care.

PMID- 15957582
TI  - Tissue engineering: an adjunct to or replacement for tissue and organ
      transplantation.

PMID- 15957583
TI  - Supervised clinical placement and legal accountability.

PMID- 15957584
TI  - Munday v Australian Capital Territory Health and Community Care Service.

PMID- 15957585
TI  - Erickson v Maguire.

PMID- 15957586
TI  - Blood rights: the body and information privacy.
AB  - Genetic and other medical technology makes blood, human tissue and other bodily
      samples an immediate and accessible source of comprehensive personal and health
      information about individuals. Yet, unlike medical records, bodily samples are
      not subject to effective privacy protection or other regulation to ensure that
      individuals have rights to control the collection, use and transfer of such
      samples. This article examines the existing coverage of privacy legislation,
      arguments in favour of baseline protection for bodily samples as sources of
      information and possible approaches to new regulation protecting individual
      privacy rights in bodily samples.

PMID- 15957587
TI  - Charting a course through difficult legislative waters: tribunal decisions on
      life-sustaining measures.
AB  - Since the enactment in Queensland of the Powers of Attorney Act 1998 (Qld) and
      the Guardianship and Administration Act 2000 (Qld), a decision can be made to
      withhold or withdraw life-sustaining medical treatment from an adult who lacks
      capacity to make such decisions for herself or himself. The Guardianship and
      Administration Tribunal of Queensland has been asked to consider the law in
      relation to these decisions on a number of occasions since the legislation was
      passed. This article explores the relevant provisions of these statutes and some
      of the difficulties that arise from how they are currently drafted. It also
      examines how the Guardianship and Administration Tribunal has dealt with
      applications to withhold or withdraw life-sustaining measures, and suggests a
      course that might avoid some of the difficulties that are inherent in
      Queensland's legislative regime.

PMID- 15957588
TI  - Court-ordered obstetrical intervention and the rights of a pregnant woman.
AB  - Cases of court-ordered obstetrical interventions are not common but have caused
      great controversy in the United States, Canada and Britain. At stake for the
      pregnant woman is her right to have autonomy over her body and control over the
      medical treatment that she receives. However, with growing medical knowledge of
      the fetal condition, there is a case to suggest that the fetus should have some
      rights in cases where the decision of the pregnant woman to refuse treatment
      would cause severe harm to the fetus. The article argues that though the case
      against intervention is extremely strong, court-ordered obstetrical interventions
      should still be possible in extreme cases.

PMID- 15957589
TI  - Criminal and civil community-based "detention": some parallels.
AB  - Over the last 20 years, governments in Australia and elsewhere have increasingly
      embraced the notion of community-based treatment of the mentally ill in
      preference to detention in a mental health facility. At the same time,
      governments have also embraced the notion of community-based treatment and
      punishment of criminal offenders in preference to detention in a custodial
      facility. This article examines the use of Community Treatment Orders (CTOs)
      within the Victorian mental health regime, and the use of Intensive Correction
      Orders (ICOs) within the Victorian criminal justice regime. It is argued that a
      number of striking similarities can be found in the respective legislative
      schemes and policy considerations.

PMID- 15957590
TI  - Fiduciary disclosure of medical mistakes: the duty to promptly notify patients of
      adverse health care events.
AB  - Fiduciary obligations are imposed by the common law to ensure that a person
      occupying a societal role with a high potential for the manipulation of
      vulnerable persons exercises utmost good faith. Australian law has recognised
      that the doctor-patient relationship, while not wholly fiduciary, has fiduciary
      aspects. Amongst such duties are those prohibiting sexual or financial abuse of
      patients or disclosure without express authority of confidential information. One
      important consequence of attaching such fiduciary duties to the doctor-patient
      relationship is that the onus of proof falls not upon the vulnerable party (the
      patient), but upon the doctor (to disprove the allegation). Another is that
      consent cannot be pleaded as an absolute defence. In this article the authors
      advocate that the law should now accept that the fiduciary obligations of the
      doctor-patient relationship extend to creating a legal duty that any adverse
      health care event be promptly reported to the patient involved. The reasons for
      creating such a presumption, as well as its elements and exceptions, are
      explained.

PMID- 15957591
TI  - Research on human embryos and cloning: difficulties of legislating in a changing
      environment and model approaches to regulation.
AB  - It is difficult to regulate rapidly changing fields of science. New technologies
      are not anticipated and legislation becomes inadequate. Legislative definitions
      are also problematic. This article begins with consideration of such difficulties
      in the context of research on human embryos and cloning. It considers problems
      with past legislative definitions in Australia, the new regulatory regime, and
      whether that regime now sets clear boundaries. It is found that problems still
      exist--some terms are not adequately defined and boundaries for research prove
      unclear. Three regulatory approaches are therefore discussed. Legislation based
      on strict definitions is compared to a legislative model that leaves terms
      undefined. The third model--which combines framework legislation with the
      oversight of a regulatory authority--is seen as most suitable. However, problems
      with this model are recognised and suggestions made regarding how to ensure the
      "framework" remains workable and effective.

PMID- 15957592
TI  - Euthanasia and assisted suicide: a liberal approach versus the traditional moral
      view.
AB  - Within the context of the debate over the recent suspended sentence given to John
      Stuart Godfrey by Underwood J in the Supreme Court of Tasmania for assisting his
      elderly mother with her suicide, this article examines some of the more popular
      arguments for and against the moral acceptability of euthanasia and assisted
      suicide. This article considers the arguments put forward on the "difference
      principle" by Rachels and Nesbitt before critically examining the liberal
      approach to the euthanasia issue as proposed by Kuhse. It is argued that whilst
      Kuhse is correct to reject the difference principle, she does so for the wrong
      reasons. The penultimate section of the article provides an overview of the
      traditional moral view against killing. The final part assesses whether the
      arguments put forward by proponents of the liberal approach are capable of
      overcoming this view.

PMID- 15957593
TI  - Missed breast cancer: the legal factors.
AB  - Any reading of the relevant legal authorities confirms the special difficulties
      involved in the diagnosis of breast cancer. In many cases a delayed diagnosis of
      breast cancer is made at a time when a patient's position has become terminal. It
      is an easy task for lawyers and expert witnesses to determine in hindsight what
      should have been done at some point in the past. This article describes how the
      courts have dealt with this issue and comments on appropriate procedures and
      approaches to both protect the interests of the patient and confine liability for
      the medical practitioner.

PMID- 15957594
TI  - Tracking of migrating cells under phase-contrast video microscopy with combined
      mean-shift processes.
AB  - In this paper, we propose a combination of mean-shift-based tracking processes to
      establish migrating cell trajectories through in vitro phase-contrast video
      microscopy. After a recapitulation on how the mean-shift algorithm permits
      efficient object tracking we describe the proposed extension and apply it to the
      in vitro cell tracking problem. In this application, the cells are unmarked
      (i.e., no fluorescent probe is used) and are observed under classical phase
      contrast microscopy. By introducing an adaptive combination of several kernels,
      we address several problems such as variations in size and shape of the tracked
      objects (e.g., those occurring in the case of cell membrane extensions), the
      presence of incomplete (or noncontrasted) object boundaries, partially
      overlapping objects and object splitting (in the case of cell divisions or
      mitoses). Comparing the tracking results automatically obtained to those
      generated manually by a human expert, we tested the stability of the different
      algorithm parameters and their effects on the tracking results. We also show how
      the method is resistant to a decrease in image resolution and accidental
      defocusing (which may occur during long experiments, e.g., dozens of hours).
      Finally, we applied our methodology on cancer cell tracking and showed that
      cytochalasin-D significantly inhibits cell motility.

PMID- 15957595
TI  - Study of temporal stationarity and spatial consistency of fMRI noise using
      independent component analysis.
AB  - Spatial independent component analysis (ICA) was used to study the temporal
      stationarity and spatial consistency of structured functional MRI (fMRI) noise.
      Spatial correlations have been used in the past to generate filters for the
      removal of structured noise for each time-course in an fMRI dataset. It would be
      beneficial to produce a multivariate filter based on the same principles. ICA is
      examined to determine if it has properties that are beneficial for this type of
      filtering. Six fMRI baseline datasets were decomposed via spatial ICA. The time
      courses associated with each component were tested for wide-sense stationarity
      using the wide sense stationarity quotient (WSS). Each dataset was divided into
      three subsets and each subset was decomposed. The components of first and third
      subset were matched by the strength of their correlation. The components produced
      by ICA were found to have largely nonstationary time-courses. Despite the
      temporal nonstationarity in the data, ICA was found to produce consistent spatial
      components. The degree of correlation among components differed depending on the
      amount of dimension reduction performed on the data. It was found that a
      relatively small number of dimensions produced components that are potentially
      useful for generating a spatial fMRI filter.

PMID- 15957596
TI  - Wavelet coding of volumetric medical images for high throughput and operability.
AB  - This paper presents a new three-dimensional (3-D) wavelet-based scalable lossless
      coding scheme for compression of volumetric medical images. Aiming to improve the
      productivity of radiologists and the cost-effectiveness of the system, we strive
      to achieve high decoder throughput, random access to coded data volume,
      progressive transmission, and high compression ratio in a balanced design
      approach. These desirable functionalities are realized by a modified 3-D dyadic
      wavelet transform tailored to volumetric medical images and an optimized Rice
      code of very low complexity.

PMID- 15957597
TI  - A stochastic model for studying the laminar structure of cortex from MRI.
AB  - The human cerebral cortex is a laminar structure about 3 mm thick, and is easily
      visualized with current magnetic resonance (MR) technology. The thickness of the
      cortex varies locally by region, and is likely to be influenced by such factors
      as development, disease and aging. Thus, accurate measurements of local cortical
      thickness are likely to be of interest to other researchers. We develop a
      parametric stochastic model relating the laminar structure of local regions of
      the cerebral cortex to MR image data. Parameters of the model include local
      thickness, and statistics describing white, gray and cerebrospinal fluid (CSF)
      image intensity values as a function of the normal distance from the center of a
      voxel to a local coordinate system anchored at the gray/white matter interface.
      Our fundamental data object, the intensity-distance histogram (IDH), is a two
      dimensional (2-D) generalization of the conventional 1-D image intensity
      histogram, which indexes voxels not only by their intensity value, but also by
      their normal distance to the gray/white interface. We model the IDH empirically
      as a marked Poisson process with marking process a Gaussian random field model of
      image intensity indexed against normal distance. In this paper, we relate the
      parameters of the IDH model to the local geometry of the cortex. A maximum
      likelihood framework estimates the parameters of the model from the data. Here,
      we show estimates of these parameters for 10 volumes in the posterior cingulate,
      and 6 volumes in the anterior and posterior banks of the central sulcus. The
      accuracy of the estimates is quantified via Cramer-Rao bounds. We believe that
      this relatively crude model can be extended in a straightforward fashion to other
      biologically and theoretically interesting problems such as segmentation, surface
      area estimation, and estimating the thickness distribution in a variety of
      biologically relevant contexts.

PMID- 15957598
TI  - Despeckling of medical ultrasound images using data and rate adaptive lossy
      compression.
AB  - A novel technique for despeckling the medical ultrasound images using lossy
      compression is presented. The logarithm of the input image is first transformed
      to the multiscale wavelet domain. It is then shown that the subband coefficients
      of the log-transformed ultrasound image can be successfully modeled using the
      generalized Laplacian distribution. Based on this modeling, a simple adaptation
      of the zero-zone and reconstruction levels of the uniform threshold quantizer is
      proposed in order to achieve simultaneous despeckling and quantization. This
      adaptation is based on: (1) an estimate of the corrupting speckle noise level in
      the image; (2) the estimated statistics of the noise-free subband coefficients;
      and (3) the required compression rate. The Laplacian distribution is considered
      as a special case of the generalized Laplacian distribution and its efficacy is
      demonstrated for the problem under consideration. Context-based classification is
      also applied to the noisy coefficients to enhance the performance of the subband
      coder. Simulation results using a contrast detail phantom image and several real
      ultrasound images are presented. To validate the performance of the proposed
      scheme, comparison with two two-stage schemes, wherein the speckled image is
      first filtered and then compressed using the state-of-the-art JPEG2000 encoder,
      is presented. Experimental results show that the proposed scheme works better,
      both in terms of the signal to noise ratio and the visual quality.

PMID- 15957599
TI  - Computer vision elastography: speckle adaptive motion estimation for elastography
      using ultrasound sequences.
AB  - We present the development and validation of an image based speckle tracking
      methodology, for determining temporal two-dimensional (2-D) axial and lateral
      displacement and strain fields from ultrasound video streams. We refine a
      multiple scale region matching approach incorporating novel solutions to known
      speckle tracking problems. Key contributions include automatic similarity measure
      selection to adapt to varying speckle density, quantifying trajectory fields, and
      spatiotemporal elastograms. Results are validated using tissue mimicking phantoms
      and in vitro data, before applying them to in vivo musculoskeletal ultrasound
      sequences. The method presented has the potential to improve clinical knowledge
      of tendon pathology from carpel tunnel syndrome, inflammation from implants,
      sport injuries, and many others.

PMID- 15957600
TI  - A registration framework for the comparison of mammogram sequences.
AB  - In this paper, we present a two-stage algorithm for mammogram registration, the
      geometrical alignment of mammogram sequences. The rationale behind this paper
      stems from the intrinsic difficulties in comparing mammogram sequences. Mammogram
      comparison is a valuable tool in national breast screening programs as well as in
      frequent monitoring and hormone replacement therapy (HRT). The method presented
      in this paper aims to improve mammogram comparison by estimating the underlying
      geometric transformation for any mammogram sequence. It takes into consideration
      the various temporal changes that may occur between successive scans of the same
      woman and is designed to overcome the inconsistencies of mammogram image
      formation.

PMID- 15957601
TI  - Nonlinear phase correction with an extended statistical algorithm.
AB  - This paper presents a new magnetic resonance imaging (MRI) phase correction
      method. The linear phase correction method using autocorrelation proposed by Ahn
      and Cho (AC method) is extended to handle nonlinear terms, which are often
      important for polynomial expansion of phase variation in MRI. The polynomial
      coefficients are statistically determined from a cascade series of n-pixel-shift
      rotational differential fields (RDFs). The n-pixel-shift RDF represents local
      vector rotations of a complex field relative to itself after being shifted by n
      pixels. We have found that increasing the shift enhances the signal significantly
      and extends the AC method to handle higher order nonlinear phase error terms. The
      n-pixel-shift RDF can also be applied to improve other methods such as the
      weighted least squares phase unwrapping method proposed by Liang. The feasibility
      of the method has been demonstrated with two-dimensional (2-D) in vivo inversion
      recovery MRI data.

PMID- 15957602
TI  - New denoising scheme for magnetic resonance spectroscopy signals.
AB  - A new scheme for denoising magnetic resonance spectroscopy (MRS) signals is
      presented. This scheme is based on projecting noisy MRS signals in different
      domains, consecutively, and performing noise filtering operations in these
      domains. The domains are chosen such that the noise portion, which is inseparable
      from the desired signal in one domain, is separable in the other. A set of
      stable, linear, time-frequency (SLTF) transforms with different resolutions was
      selected for these projections as an example. Scheme evaluation was performed
      using extensive MRS signals with various noise levels. Compared with one domain
      denoising, it was observed that the proposed scheme gives superior results that
      compensate for the excess computational requirements. The proposed scheme
      supersedes also the wavelet packet denoising schemes.

PMID- 15957603
TI  - Weighted expectation maximization reconstruction algorithms for thermoacoustic
      tomography.
AB  - Thermoacoustic tomography (TAT) is an emerging imaging technique with potential
      for a wide range of biomedical imaging applications. In this correspondence, we
      propose an infinite family of weighted expectation maximization (EM) algorithms
      for reconstruction of images from temporally truncated TAT measurement data. The
      weighted EM algorithms are equivalent mathematically to the conventional EM
      algorithm, but are shown to propagate data inconsistencies in different ways.
      Using simulated and experimental TAT measurement data, we demonstrate that
      suitable choices of weighted EM algorithms can effectively mitigate image
      artifacts that are attributable to temporal truncation of the TAT data function.

PMID- 15957604
TI  - New nursing practice statement NP 81: the nurse as a volunteer.

PMID- 15957605
TI  - From CAN: accountability and liability in professional nursing practice.

PMID- 15957606
TI  - Auto-immune-like cone dystrophy.
AB  - PURPOSE: To describe rapid loss of cone vision in an adult due to putative auto
      immune rejection. METHODS: Clinical and electrophysiological examination,
      including full-field and multi-focal electroretinograms (ERGs), were used to
      assess retinal function. Serum was analyzed for antibodies to retinal antigens.
      RESULTS: The patient lost cone vision in the course of several months while rod
      vision remained unaffected. Initially short wavelength (S) cone function appeared
      more resistant to the degeneration. Cancer associated retinal antibodies were
      present in the sera of the patient but no cancer has been found. CONCLUSION:
      Rapid loss of cone function can occur in an adult without a concomitant neoplasm
      although serum antibodies to retinal antigens suggest an autoimmune cause.

PMID- 15957607
TI  - Pattern VEP is a useful technique in monitoring the effectiveness of occlusion
      therapy in amblyopic eyes under occlusion therapy.
AB  - PURPOSE: To evaluate the effectiveness and clinical significance of pattern
      visual evoked potential (P-VEP) parameters on visual acuity in amblyopic patients
      under occlusion therapy. METHODS: A total of 34 consecutive children with
      anisometropic amblyopia were included in this study. All patients underwent a
      full initial ophthalmologic and orthoptic evaluation. P-VEP test was performed in
      all cases and binocular vision was tested and recorded with Worth's four-dot test
      and Bagolini striated glasses at each visit. Part-time occlusion therapy was
      performed by using adhesive patches. RESULTS: The mean (+/- SEM) cycloplegic
      refractive error was + 5.6 +/- 0.6 diopters (D) in the amblyopic eyes and + 1.8
      +/- 0.2 D in the normal eye. The mean levels of best-corrected visual acuity were
      statistically differed between each measurement for occlusion therapy (for each,
      p < 0.05). The ratio of the patients with binocular vision increased after 6
      months occlusion therapy and the difference was statistically significant (p <
      0.05). In addition, P100 amplitude improved at each visit and the difference was
      significant when compared with baseline values (for each, p < 0.05). CONCLUSIONS:
      P100 amplitude of the P-VEP test parallels the improvement in subjective visual
      acuity in amblyopic eyes under occlusion therapy. Therefore, this test may be
      useful in monitoring the visual acuity in the preverbal or non-verbal patched
      patients.

PMID- 15957608
TI  - Effect of defocusing and of distracted attention upon recordings of the visual
      evoked potential.
AB  - Pattern reversal visual stimuli are used to evoke potentials (VEPs) for
      assessment of visual acuity and for localizing defects along the visual pathways.
      Our goal was to assess the importance of attention and defocusing to the
      recordings of pattern VEP. Forty-one volunteers with normal (6/6) corrected
      visual acuity participated in this study. Twenty-one were asked to defocus
      intentionally the visual stimulus (located 200 cm away) by fixating at a target
      25 or 50 cm from the eye. Twenty other subjects performed auditory tasks to
      distract their attention from the visual stimulus. Pattern VEPs were elicited by
      different check sizes. The amplitude and time-to-peak of the P100 wave were
      measured. Intentional defocusing caused amplitude reduction and prolongation of
      the time-to-peak in young subjects (20-34 years old). With the smallest checks
      used (7.5') we could not record a reliable response from 43% of the young
      subjects (6 out of 14). In older patients (35-61 years old), intentional
      defocusing induced negligible effects on pattern VEPs regardless of check size.
      There were no effects of auditory distraction upon the pattern VEPs. Our data
      suggest that intentional defocusing can produce false positive results (reduced
      VEP with prolonged time-to-peak) only when small checks are used in young
      subjects. Divided attention has negligible effect on the recordings of pattern
      VEPs. With proper controls, the pattern VEP test can be used for objective
      assessment of visual function.

PMID- 15957609
TI  - Methods of visual acuity determination with the spatial frequency sweep visual
      evoked potential.
AB  - PURPOSE: The spatial frequency sweep visual evoked potential (sVEP) is used to
      rapidly determine visual acuity in children or non-responsive patients. Two
      techniques have been used to separate signal from noise: (1) the 95% confidence
      interval for the signal amplitude (95% CI) or (2) the amplitude of a Fourier
      frequency adjacent to 2x the signal frequency (DFT). The purpose of this study is
      to determine if there is a significant difference in acuity estimates with these
      techniques. METHODS: Ten normal subjects (approximately 0.00 logMAR acuity) and
      11 patients with decreased visual acuity took part in this project. Stimulus
      production and data analysis were done with an Enfant 4010 (Neuroscientific
      Corp). Standard VEP recording techniques were employed. The stimulus was a
      horizontal-oriented, sine wave grating that swept up the spatial frequency
      spectrum (contrast 80%, temporal reversal rate 7.5 Hz). Sweeps were repeated
      until the confidence intervals for the data were no longer decreasing. The Bailey
      Lovie logMAR chart was used to determine visual acuity. A line was fit to the
      high spatial frequency data using either the 95% CI or the DFT as the noise
      estimate. By using these linear equations, acuity estimates were obtained at 0,
      1, and 2 microV signal amplitudes. RESULTS: The average logMAR acuity for the
      subjects with normal acuity was -0.06 +/- 0.070 (SD). The sVEP acuity estimates
      were 0.08 +/- 0.098, 0.18 +/- 0.092, and 0.33 +/- 0.195 (0, 1, and 2 microV
      extrapolations) with the 95% CI used as noise and 0.07 +/- 0.100, 0.18 +/- 0.103,
      and 0.33 +/- 0.202 (0, 1, and 2 microV extrapolations) with the DFT used as
      noise. By using the average noise from the Fourier frequency as the extrapolation
      level, the acuity was 0.10 +/- 0.098 logMAR. The average logMAR acuity for the
      subjects with decreased visual acuity was 0.67 +/- 0.306 (SD). The sVEP acuity
      estimates were 0.53 +/- 0.175, 0.66 +/- 0.171, and 0.88 +/- 0.295 (0, 1, and 2
      microV extrapolations) with the 95% CI used as noise and 0.53 +/- 0.179, 0.65 +/-
      0.176, and 0.86 +/- 0.268 (0, 1, and 2 microV extrapolations) with the DFT used
      as noise. By using the average noise from the Fourier frequency as the
      extrapolation level, the acuity was 0.57 +/- 0.186 logMAR. No significant
      difference was found between the two acuity estimate techniques for all of the
      subjects (repeated measures ANOVA, p = 0.16, F20 = 2.131). The sVEP estimates of
      acuity to the 0 microV and noise levels were not significantly different from the
      logMAR acuity (paired t-test, all p values > 0.05). CONCLUSIONS: The results
      indicate that the sVEP acuity does not depend on the noise estimation technique.
      In agreement with prior studies, the sVEP acuity underestimates the logMAR acuity
      in normally sighted individuals by about an octave.

PMID- 15957610
TI  - Morphological and functional changes of the macula after vitrectomy and creation
      of posterior vitreous detachment in eyes with diabetic macular edema.
AB  - The purpose of this study was to determine the morphological and functional
      changes in the macula after pars plana vitrectomy with the creation of a
      posterior vitreous detachment in eyes with diabetic macular edema (DME). A simple
      posterior vitreous detachment was created during pars plana vitrectomy
      accompanied by simultaneous cataract surgery in 19 eyes of 17 patients with DME.
      The visual acuity (log MAR units), multifocal electroretinograms (mfERGs), and
      optical coherence tomographically (OCT)-determined foveal thickness were
      determined preoperatively and at 6 months postoperatively. The median
      preoperative log MAR visual acuity was 0.7 (20/100; range, 0.3-1.1), and it
      improved significantly to 0.4 (20/50; range, 0.15-1.0) postoperatively (p =
      0.016). The median foveal thickness was 510 (range, 194-800) microm
      preoperatively and was significantly reduced to 201 (range, 60-631) microm
      postoperatively (p =0.0002). The median of response density of the mfERGs in the
      macular area was 6.3 nV/ deg2 (range, 2.8-14.8) preoperatively, and 6.1 nV/deg2
      (range, 2.4-14.3) postoperatively, a non-significant change (p = 0.27). The
      median of peak latency of the macular response was 30.0 ms (range, 25.0-44.2)
      preoperatively and it decreased significantly to 28.3 ms (range, 26.7-35.0)
      postoperatively (p = 0.003). In conclusion, vitrectomy with the creation of a PVD
      in eyes with DME improved the visual acuity and foveal thickness significantly.
      In addition, a decrease of the peak latency of the macular mfERGs suggested an
      improvement of the physiological function of the macula although the amplitude of
      the mfERGs was not changed significantly.

PMID- 15957611
TI  - Test-retest reliability of the multifocal electroretinogram and humphrey visual
      fields in patients with retinitis pigmentosa.
AB  - We examined the reliability of Humphrey visual field thresholds and multifocal
      electroretinogram (mfERG) amplitudes and timing in a group of patients with
      Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were
      tested five times: at baseline (visit #0), at three weekly follow-up visits
      (visits #1 - #3), and at three months (visit #4). For the Humphrey thresholds,
      differences between dB values on repeat visits were obtained. Differences between
      log values on repeat visits were calculated for mfERG amplitude and implicit
      time. We used the standard deviations of these difference scores as a measure of
      reliability and the means of the difference scores as a measure of progression.
      We found that the majority of the patients' repeat data were more variable than
      that of the control subjects for both the Humphrey and mfERG. We found no single
      factor that predicted the magnitude, or the variance, of the SD of differences
      scores for the patients. We recommend that each patient's reliability be assessed
      individually. Ultimately, the choice of an outcome measure must be guided by its
      reliability, as well as its ability to assess the visual function of interest.

PMID- 15957612
TI  - EOG as a monitor of desferrioxamine retinal toxicity.
AB  - Iron overload caused by blood transfusion-dependent anaemia usually results in
      lethal cardiac toxicity unless treated by iron-chelation therapy. Chelation
      therapy with desferrioxamine (DFO) is well established and widely used to remove
      excess iron. Unfortunately, visual disorders have been recorded after DFO
      infusion. In this investigation, a 61-year-old Caucasian female received DFO for
      her autoimmune haemolytic anaemia. Prior to starting with the DFO treatment, her
      baseline ophthalmic screening and electrooculogram (EOG) were completely normal.
      Two years later she noticed a grey scotoma in her right eye. Visual acuity in
      this eye was reduced from 6/5 to 6/9 and funduscopy revealed evidence of non
      specific mottling of the retinal pigment epithelium of both retinae. The EOG was
      flat (106%) in the right eye and subnormal in the left (155%). The lower limit of
      our EOG Arden Ratio for normal subjects is 180%. After her DFO treatment was
      stopped, her right visual acuity returned to 6/5, her field tests showed
      progressive improvement bilaterally and the EOG went back to the normal range.
      While waiting for splenectomy, the patient was restarted on a lower dose of DFO
      and EOG measurements were carried out every two (or three) weeks to monitor for
      DFO toxicity. The EOG varied during this period indicating some deterioration of
      function in the retinal pigment epithelium. However, normalisation of the EOG
      values (right = 217%, left = 217%) occurred after splenectomy and cessation of
      DFO therapy. Her visual function was normal and her visual acuity 6/4 bilateral
      when she was discharged from our outpatient clinic. On reviewing her history it
      was apparent that the EOG was the most sensitive indicator of DFO toxicity.

PMID- 15957613
TI  - Acquired subretinal flecks secondary to hypovitaminosis A in a patient with
      hepatitis C.

PMID- 15957614
TI  - [Small cell bronchial carcinoma. Main symptoms: cough, hemoptysis, hoarseness,
      dyspnea, paraneoplastic syndrome., weight loss, neurologic manifestations and
      post-stenotic pneumonia].

PMID- 15957615
TI  - [Chronic pancreatitis--pancreas cancer: influence of genetic factors].
AB  - Chronic pancreatitis: Only recently mutations in several genes were found in
      patients with chronic pancreatitis. In those with a familial chronic pancreatitis
      mutations of the cationic trypsinogen were identified and the variants N29I and
      R122H lead to an autosomal dominant disease. In this group of patients the
      mutation N34S of the trypsin inhibitor SPINK1 was detected. In so-called
      idiopathic pancreatitis both variants of the SPINK1 and of the CFTR (cystic
      fibrosis transmembrane conductance regular) were identified. Alterations in both
      genes were also found in patients with alcoholic chronic pancreatitis. The
      strongest risk factor for chronic pancreatitis were trypsinogen mutations N29I
      and R122H mutations. However, both SPINK1 and CFTR increased the risk for chronic
      pancreatitis to a higher level than alcohol consumption. A genetic investigation
      should be performed in familial disease and younger age, but also in patients
      without family history and higher age a mutation could be found. Pancreas cancer:
      In 10% of the patients with pancreas cancer other members of the family were
      affected from the disease. Some of them belong to well characterized familial
      syndroms like HNPCC or Peutz-Jeghers-syndrom. In a minority of the others a
      genetic factor may be found, too. In sporadic disease the development of the
      tumor is characterized by continued acquirement of genetic alterations described
      by the PanIN model (pancreatic intraepithelial neoplesia). This means that the
      evolution of the neoplasia progresses from normal tissue via epithelial
      hyperplasy (PanIN 1A), papillary hyperplasy without (PanIN 1B) and with dysplasy
      (PanIN 2) and carcinoma in situ (PanIN 3) to invasive pancreas cancer. The
      progression is associated with genetic alterations of the cells (mutations of ki
      ras, p16, p53 etc.). This results in deterioration of control of the cell cycle
      and the apoptosis and explains the malignancy of the disease. These findings may
      be used in the future to develop newer therapeutic principles in order to improve
      the dismal prognosis of this disease.

PMID- 15957616
TI  - [Acute pancreatitis: diagnosis and conservative therapy].
AB  - Despite our increasing knowledge in pathophysiology of acute pancreatitis
      therapeutic strategies based on this knowledge, such as inhibition of proteases,
      are non convincing. It is most likely that these strategies are initiated to late
      after the onset of pancreatitis. It is of utmost importance to clarify the
      severity of the disease for planning interdisciplinary approaches: therapy of
      pain, enteral nutrition via a jejunal tube, treatment of extrapancreatic
      complications, such as respiratory insufficiency, coagulopathy, renal
      insufficiency. A key role plays the exact balance of potential high fluid losses.
      Prophylactic application of antibiotics such as imipenem, in necrotizing
      pancreatitis to prevent infection is widely used. Infected necroses are an
      indication for surgery. In biliary pancreatitis one has to remove impacted bile
      duct stones via ERCP and papillotomy followed by elective cholecystectomy.

PMID- 15957617
TI  - [Acute pancreatitis: surgical therapy].
AB  - Today, treatment of acute pancreatitis is mainly conservative and surgery is on
      the retreat. Infection of pancreatic necrosis is still the main risk factor of
      morbidity and mortality in the course of necrotizing disease. A prophylactic
      treatment with antibiotics can reduce both infectious complications and
      mortality. Thus, antibiotics should be administered in severe pancreatitis. If
      pancreatic infection is suspected, fine needle aspiration should be performed.
      Today, infected pancreatic necrosis is a well accepted indication for surgery.
      Aim of the surgical procedure is to remove the septic focus by debridement of the
      infected pancreatic and peripancreatic necrosis. The optimal timepoint for the
      surgical intervention is after the third week after onset of the disease. At that
      time, necrotic tissue is well demarcated. Therefore bleeding complications and
      removal of vital tissue can be avoided. Today, surgical procedures should combine
      the necrosectomy with a postoperative method to continuously remove necrosis and
      debris. This is the case with the following two techniques, the postoperative
      continuous lavage and the closed packing.

PMID- 15957618
TI  - [Conservative treatment of chronic pancreatitis].
AB  - Chronic pancreatitis represents an inflammatory disease of the pancreas with
      progressive fibrotic destruction of the gland. The disease is characterized by
      abdominal pain, exocrine and endocrine insufficiency. Morphological alterations
      of the pancreas and signs of exocrine and endocrine insufficiency are difficult
      to detect early in the course of the disease. The conservative treatment of
      chronic pancreatitis aims at (1) control of abdominal pain, (2) replacing lost
      exocrine function, (3) treatment of endocrine insufficiency, (4) prevention of
      weight loss or achievement of weight gain, (5) limiting progression and
      complications of the disease, and finally (6) psychiatric and social advice with
      special emphasis on the treatment of chronic alcohol abuse. The patient must be
      counselled about the importance of abstinence from alcohol. Abdominal pain is
      controlled with strict analgetic medication using a step-by-step approach in
      increasing the dosage. Exocrine insufficiency is treated with a diet of several
      small meals per day and supplementation of pancreatic enzymes. Endocrine
      insufficiency is treated with insulin.

PMID- 15957619
TI  - [Yams: food, drug or both?].

PMID- 15957620
TI  - An algorithm for the detection of individual breaths from the pulse oximeter
      waveform.
AB  - OBJECTIVES: To determine if wavelet analysis techniques can be used to reliably
      identify individual breaths from the photoplethysmogram (PPG). METHODS:
      Photoplethysmograms were obtained from 22 healthy adult volunteers timing their
      respiration rate in synchronisation with a metronome. A secondary timing signal
      was obtained by asking the volunteers to actuate a small push button switch, held
      in their right hand, in synchronisation with their respiration. Each PPG was
      analyzed using primary wavelet decomposition and two new, related, secondary
      decompositions to determine the accuracy of individual breath detection. RESULTS:
      The optimal breath capture was obtained by manually polling the three techniques,
      allowing detection of 466 out of the 472 breaths studied; a detection rate of
      98.7% with no false positive breaths detected. CONCLUSION: Our technique allows
      the accurate capture of individual breaths from the photoplethysmogram, and leads
      the way for developing a simple non-invasive combined respiration and saturation
      monitor.

PMID- 15957621
TI  - A new non-invasive continuous cardiac output trend solely utilizing routine
      cardiovascular monitors.
AB  - OBJECTIVE: Three of the us developed a new non-invasive continuous cardiac output
      (CCO) measurement method utilizing routine clinical monitors based on the pulse
      contour analysis combined with pulse wave transit time (PWTT). Using pulmonary
      artery catheter (CCOpa), we compared this estimated CCO (esCO) with the
      thermodilution CCO early after cardiac surgery, and tested whether the esCO
      method has potential of being an alternative measure of CCO. METHODS: Thirty-six
      patients without continued arrhythmias were studied. esCO was computed using
      electrocardiogram (ECG) monitor, arterial pressure monitor and pulse-oximetry
      system. Both sets of data (esCO and CCOpa), by averaging the results of the
      preceding 10 min, were compared at 30-min intervals throughout the 15.8 +/- 3.3 h
      (S.D.) of study. Bland-Altman plots and correlation analysis were used for
      statistical comparison. RESULTS: A total of 981 paired sets of data (89.9%) among
      1093 measurements were compared in the absence of displacement of either pulse
      oximetry or ECG probes and/or inaccurate detection of R wave. The difference
      between esCO and CCOpa results was -0.06 +/- 0.82 L/min (S.D.), and there was a
      linear correlation between them (r = 0.80, p < 0.0001). The difference between
      them was 0.00 +/- 0.48 L/min at the first 1 h, which remained unchanged
      throughout 20 h after the start of measurement. CONCLUSIONS: The results
      demonstrate that esCO has a close correlation with the CCOpa, even though the two
      methods are not interchangeable. The results suggest that esCO method has
      potential of being an alternative non-invasive cardiac output trend, unless there
      are apparent arrhythmias.

PMID- 15957622
TI  - Nitrogen diffusion into closed anesthesia systems.
AB  - OBJECTIVE: In order to reduce losses of gases through plastic components and to
      reduce nitrogen accummulation during closed system anaesthesia we investigated
      either 10 sets of anaesthetic tubing made of silicon as used in standard clinical
      practice and 10 sets made of latex, which are not used anymore due to concerns
      about latex allergies. The results were compared to each one set made of
      conventional industrial rubber. METHODS: Anaesthetic tubings were connected to
      ventilators with low fresh gas losses, suitable for closed system anaesthesia.
      For nitrogen measurements, a mass spectrometer was used. The fresh gas flow was
      set to exceed losses by leakages and the amount of gases, extracted from the
      system by the mass spectrometer. RESULTS: Highest accumulation of nitrogen was
      found using tubings made of silicone. CONCLUSION: If closed anaesthetic systems
      in the future will be used in intensive care therapy or in case of long lasting
      procedures in which closed system anaesthesia is proceeded, materials other than
      silicone should be investigated to avoid regular purging of system and
      consecutive losses of gas mixtures.

PMID- 15957623
TI  - Calculation of O2 consumption during low-flow anesthesia from tidal gas
      concentrations, flowmeter, and minute ventilation.
AB  - We present the principles of a new method to calculate O2 consumption (V*O2)
      during low-flow anesthesia with a circle circuit when the source gas flows, end
      tidal O2 concentrations and patient inspired minute ventilation are known. This
      method was tested in a model with simulated O2 uptake and CO2 production. The
      difference between calculated V*O2 and simulated V*O2 was 0.01 +/- 0.02 L/min. A
      similar approach can be used to calculate uptake of inhaled anesthetics. At
      present, with this method, the limiting factor in precision of measurement of
      V*O2 and uptake of anesthetic is the precision of measurement of gas flow and gas
      concentration (especially O2 concentration in end-tidal gas, FETO2) available in
      clinical anesthetic units.

PMID- 15957624
TI  - Pulse transit time by R-wave-gated infrared photoplethysmography: review of the
      literature and personal experience.
AB  - OBJECTIVE: Pulse transit time (PTT) is the time it takes a pulse wave to travel
      between two arterial sites. A rela tively short PTT is observed with high blood
      pressure (BP), aging, arteriosclerosis and diabetes mellitus. Most methods used
      for measuring the PTT are cumbersome and expensive. In contrast, the interval
      between the peak of the R-wave on the electrocardiogram and the onset of the
      corresponding pulse in the finger pad measured by photoplethysmography can be
      easily measured. We review herein the literature and impart the experience at our
      institution on clinical applications of R-wave-gated photo-plethysmography (RWPP)
      as measurement of PTT. METHODS: The MEDLINE data base on clinical applications of
      RWPP was reviewed. In addition, studies performed in the author's institution are
      presented. RESULTS: When used as a surrogate for beat-to-beat BP monitoring, RWPP
      did not meet the level of accuracy required for medical practice (two studies).
      RWPP produced accurate and reproducible signals when utilized as a surrogate for
      intra-thoracic pressure changes in obstructive sleep apnea, as well as BP
      arousals which accompany central sleep apnea (five studies). In estimation of
      arterial stiffness, RWPP was unsatisfactory (one study). In assessment of
      cardiovascular reactivity, abnormal values of RWPP were noted in autonomic
      failure (one study), while disease-specific reactivity patterns were identified
      utilizing a method involving RWPP (two studies). CONCLUSIONS: In clinical
      practice, sleep-apnea may be accurately monitored by RWPP. RWPP seems to reflect
      autonomic influences and may be particularly well-suited for the study of
      vascular reactivity. Thus, further descriptions of disease-specific
      cardiovascular reactivity patterns may be possible with techniques based on RWPP.
      Other clinical uses of RWPP are investigational.

PMID- 15957625
TI  - Initial transcutaneous PCO2 overshoot with ear probe at 42 degrees C.
AB  - OBJECTIVE: To investigate an unexpectedly high initial skin CO2 pressure with a
      new small earlobe probe* heated to 42 degrees C containing both transcutaneous
      (tcPCO2) and pulse oximeter saturation (SpO2) sensors. METHODS: The probe was
      mounted on the ear lobe of six patients during abdominal or thoracic surgery and
      on several awake volunteers. The probe was mounted on a cheek or forearm in two
      other volunteers. Patients were artificially ventilated under general anesthesia
      at constant end-expiratory PCO2. RESULTS: In patients, at 8 +/- 3 min after
      mounting, tcPCO2 peaked 5 mmHg higher than its final value (p = 0.0067, n = 6,
      paired t-test). After 25 min, tcPCO2 was not different from PaCO2 (arterial).
      Similar overshoots were recorded with this device when mounted on the arm or
      cheek and with a standard transcutaneous PCO2 probe set to 42 degrees C, mounted
      on the ear lobe, arm or chest of awake volunteers. In two volunteers, we found
      that heating the sensor to 45 degrees C for the first 15 min on the ear, and then
      decreasing it to 42 degrees C prevented overshoot, and provided valid tcPCO2 data
      3 - 5 min after application of the sensor. CONCLUSIONS: A temperature of 42
      degrees C may increase local skin temperature and metabolism before vasodilating
      more remote arteriolar control of sub-sensor capillary flow. We suggest that
      transcutaneous PCO2 probes be initially set to 44 - 45 degrees C for 5 - 15 min
      to induce prompt vasodilation to prevent this overshoot and then reduced to 42
      degrees C to avoid skin thermal injury in case of long-term application.

PMID- 15957626
TI  - The effects of two different anaesthesia techniques on bispectral index values
      and awareness during off-pump coronary artery bypass grafting.
AB  - OBJECTIVE: The aim of this study was to evaluate Bispectral Index values and
      awareness during two different anaesthesia regimens (fentanyl-propofol and
      fentanyl-midazolam) in patients undergoing off-pump CABG surgery. METHODS: Fifty
      patients were included in the study. Patients were premedicated with midazolam
      and were randomly divided into two groups. Anaesthesia was induced with fentanyl
      (7-15 microg/kg), with either propofol (2 - 2.5 mg/kg, Group I) or midazolam (0.1
      - 0.3 mg/kg, Group II) and vecuronium (0.1 mg/kg). Anaesthesia was maintained
      with fentanyl (15 microg/kg/h) together with either propofol (6 mg/kg/h) or
      midazolam (0.1 mg/kg/h). Depth of anaesthesia was adjusted according to clinical
      signs and haemodynamic responses. The level of sedation was monitored with
      Bispectral index continuously, but these levels were not shown to the attending
      anaesthetist. Bispectral index values were recorded for nine phases. Twenty-four
      hours after the operation, the patients were interviewed to determine
      intraoperative awareness and recall. RESULTS: In all patients, Bispectral index
      values were found to decrease after induction (in Group I, p = 0.005, in Group
      II, p = 0.008) with the mean values remaining below 60 for all phases. The
      differences between the groups were not statistically significant in inter-group
      comparison. No patients were noted to recall the sounds presented during the
      operation and the preoperative events. CONCLUSIONS: BIS monitoring with clinical
      signs may be used to assess the adequacy of both types of anaesthesia techniques
      as well as to detect awareness during off-pump CABG surgery.

PMID- 15957627
TI  - Interactive simulation system for artificial ventilation on the internet: virtual
      ventilator.
AB  - OBJECTIVE: To develop an interactive simulation system "virtual ventilator" that
      demonstrates the dynamics of pressure and flow in the respiratory system under
      the combination of spontaneous breathing, ventilation modes, and ventilator
      options. The simulation system was designed to be used by unexperienced health
      care professionals as a self-training tool. METHODS: The system consists of a
      simulation controller and three modules: respiratory, spontaneous breath, and
      ventilator. The respiratory module models the respiratory system by three
      resistances representing the main airway, the right and left lungs, and two
      compliances also representing the right and left lungs. The spontaneous breath
      module generates inspiratory negative pressure produced by a patient. The
      ventilator module generates driving force of pressure or flow according to the
      combination of the ventilation mode and options. These forces are given to the
      respiratory module through the simulation controller. RESULTS: The simulation
      system was developed using HTML, VBScript (3000 lines, 100 kB) and ActiveX
      control (120 kB), and runs on Internet Explorer (5.5 or higher). The spontaneous
      breath is defined by a frequency, amplitude and inspiratory patterns in the
      spontaneous breath module. The user can construct a ventilation mode by setting a
      control variable, phase variables (trigger, limit, and cycle), and options.
      Available ventilation modes are: controlled mechanical ventilation (CMV),
      continuous positive airway pressure, synchronized intermittent mandatory
      ventilation (SIMV), pressure support ventilation (PSV), SIMV + PSV, pressure
      controlled ventilation (PCV), pressure-regulated volume control (PRVC),
      proportional assisted ventilation, mandatory minute ventilation (MMV), bilevel
      positive airway pressure (BiPAP). The simulation system demonstrates in a graph
      and animation the airway pressure, flow, and volume of the respiratory system
      during mechanical ventilation both with and without spontaneous breathing.
      CONCLUSIONS: We developed a web application that demonstrated the respiratory
      mechanics and the basic theory of ventilation mode.

PMID- 15957628
TI  - Usability evaluation of a GUI prototype for a ventilator machine.
AB  - OBJECTIVE: Information presentation on the monitor screen of ventilator machines
      affects nurses' response and decision-making during ventilation treatment. The
      purpose of this study is to evaluate whether a new GUI (graphical user interface)
      prototype, the so-called circular display prototype can make deviations easy to
      detect. METHOD: A numerical display prototype was made and used as a reference
      display in the evaluation. Six task scenarios that involved parameter changes
      were selected to simulate a real situation under volume control (VC) mode during
      ventilation treatment. Usability tests with the two display designs were carried
      out in a usability laboratory. Twenty medical nursing students participated as
      test subjects in the usability tests. RESULTS: The objective results showed that
      the graphical circular display had an advantage over the numerical display in
      interpreting parameter changes, but not in reducing the error rates for detecting
      the number of parameter changes or for forming an overall picture of the
      patient's situation. Furthermore, the circular display prototype did not improve
      the detection time. CONCLUSIONS: Although the majority of the test subjects
      preferred the graphical circular display, the results implied that several
      aspects of this prototype should be improved in a future development study.

PMID- 15957629
TI  - Agreement of an inert gas rebreathing device with thermodilution and the direct
      oxygen Fick method in measurement of pulmonary blood flow.
AB  - OBJECTIVE: Inert gas rebreathing is a well established method for the non
      invasive measurement of pulmonary blood flow. We tested the agreement in
      measurement of pulmonary blood flow (Qt rb) by a new inert soluble gas
      rebreathing device, the Innocor (Innovision, Copenhagen), with bolus
      thermodilution (Qt td) and the direct oxygen Fick (Qt Fick) method. METHODS: 9
      patients pre- and post-cardiac surgery were recruited resulting in 20 sets of
      measurements overall. Arterial and mixed venous blood samples were collected
      simultaneously with a thermodilution measurement and rebreathing manoeuvre to
      measure both V*O2 and effective pulmonary capillary blood flow. RESULTS: Mean
      bias (95% confidence limits) was: Qt rb - Qt td 0.01 (+/- 0.42) L/min; Qt rb - Qt
      Fick + 0.34 (+/-0.59) L/min. The standard deviation of the difference between
      paired measurements was: Qt td - Qt rb +/- 0.89 L/min; Qt Fick - Qt rb +/- 1.26
      L/min. CONCLUSIONS: Acceptable overall agreement between the Innocor and these
      reference standards was demonstrated.

PMID- 15957631
TI  - Leading change. The basics for leaders.

PMID- 15957630
TI  - Novel hand-held device for exhaled nitric oxide-analysis in research and clinical
      applications.
AB  - Changes in expired nitric oxide (NO) occur in airway inflammation and have proved
      to be important in the monitoring of inflammatory disease processes such as
      asthma. We set out to develop a novel hand-held NO-analyzer with a performance
      comparable to the present more costly and complex chemiluminescence instruments.
      The new device is based on a specially designed electrochemical sensor, where we
      have developed a novel sampling and analysis technology, compensating for the
      relatively slow response properties of the electrochemical sensor technique. A
      Lowest Detection Limit in NO-analysis from reference gas tests of less than 3 ppb
      and a response time of 15 seconds together with an average precision in human
      breath measurements of 1.4 ppb were obtained. We also show an agreement with the
      existing 'gold standard' FENO measurement technique, within 0.5 ppb in a group of
      19 subjects together with a high linearity and accuracy compared to reference
      gases. The new analyzer enables affordable monitoring of inflammatory airway
      diseases in research and routine clinical practice.

PMID- 15957632
TI  - What is a picture worth?

PMID- 15957633
TI  - The digital diagnosis: a business plan for turning technology into smiles.

PMID- 15957634
TI  - Replacing congenitally missing maxillary lateral incisors: assessing treatment
      options and case report.

PMID- 15957635
TI  - Treatment planning for dental implants: a rationale for decision making. Part 1:
      Total edentulism.

PMID- 15957636
TI  - A placement technique for creating ideal contours and aesthetics for adjacent
      multisurface posterior composites.

PMID- 15957637
TI  - Material selection: a case report.

PMID- 15957638
TI  - Simplified solutions to daily anterior aesthetic challenges using a nano
      optimized direct restorative material.

PMID- 15957639
TI  - Creating endodontic efficiencies: slippin' and slidin' or just sloggin'.

PMID- 15957640
TI  - The cone fit: an essential step to creating exceptional endodontic obturation.

PMID- 15957641
TI  - A successful approach to the management of children: Part 3.

PMID- 15957642
TI  - New ideas for avulsed tooth reimplantation.

PMID- 15957643
TI  - Advantages of electric-driven handpieces during tooth preparation.

PMID- 15957644
TI  - A journey like no other!

PMID- 15957645
TI  - E-services: the business case for implementation in today's dental practice.

PMID- 15957646
TI  - Dental digital photography '05: top five frequently asked questions.

PMID- 15957647
TI  - [From the Hippocratic Oath to the Declaration of Helsinki in times of budgets and
      DRG].
AB  - In the present healthcare system, the physician directly involved in patient care
      faces developments that are difficult to reconcile with his daily medical
      activity. He must face that the free choice of a doctor is undermined by access
      restriction and regulation. The focus of his activity shifts from classical
      medical examination to documentation and administration of the patients. His
      professional freedom of action is reduced by economic constraints. The thinning
      of the political responsibility has the consequence that he is left alone in
      communicating negative developments to the patients. The culture of clinical
      research is also increasingly under the pressure of economic constraints. While
      it must be demanded that physicians adapt to new developments, this must not
      completely undermine the basic principles of the medical profession.

PMID- 15957648
TI  - [Definition and scope of medical professional law].
AB  - Medical professional law can be defined as the sum of rules and standards that
      regulate access to, and the practice of, the medical profession. The medical
      profession is classified as a liberal profession in this context, not only from
      the professional and sociological point of view, but also from the constitutional
      and legal standpoint. The scope of medical professional law can be defined
      vertically and horizontally: on the one hand, with regard to the vast number of
      rules to which the physician is subject under the regulations of professional law
      and, on the other hand, with regard to regulations in special law, which conflict
      with other statutory provisions that are, in turn, either influenced by
      professional law (e.g. the law on contract physicians in Book V of the German
      Social Security Code) or themselves influence professional law by subjecting it
      to limitations (e.g. Art. 12 Para. 1 German Basic Law or European Community law).

PMID- 15957649
TI  - [Problems of occupational-court proceedings].
AB  - Regulations concerning disciplinary jurisdiction for the professions belong to
      the legislative authority of the federal states of the Federal Republic of
      Germany. Comprehensive regulation of professional duties may be accepted, as far
      as professional conduct is concerned. For conduct outside one's profession
      however, such a global approach to regulation appears to be questionable. Local
      intersections of competence have to be dissolved according to the principles of
      the constitutional state under the rule of law. Has the conduct constituting the
      basis of the proceedings already been avenged otherwise, it is compulsory to
      appropriately take into consideration all punishments or measures already
      administered. Ascertainment of lack of professional dignity by professional
      disciplinary courts may be problematic due to jurisdictional conflicts.

PMID- 15957650
TI  - [Limits of physician duties from the standpoint of a physician].
AB  - The occupational regulations in medicine list four professional duties. Their
      recognisable limits are not rigid, and in certain situations can (or even must)
      be crossed in both directions. The main demand concerns the carefulness
      (accuracy) of the doctor in practising his profession. This leads to formation of
      and compliance wiith medical standards. These emerge from the medical literature
      and from the recommendations of medical societies. Guidelines represent the
      elevated standard of the medical specialities. Deliberate exceptions to a
      standard rule require the informed consent of the patient, who can refuse thee
      treatment proposals. The physician can also refuse to treat a patient if he has
      well-founded reasons. However, he is obliged to provide emergency care and carry
      out acute measures. Borderline situations may arise in the field of medical
      information professional discretion, and documentation duty. The present paper
      illustrates and discusses some typical borderline situaticons.

PMID- 15957651
TI  - [Medical occupational law--limits of medical duties from a legal viewpoint].
AB  - The medical profession is not a trading business. The privileged position that
      society concedes to the medical professionals has a price: responsibility. The
      responsible professional can demand freedom as long as he does not abuse this
      freedom. Professional rules mark the border. These, however, are not only a tie,
      but also a protection against interference with medical independence.

PMID- 15957652
TI  - [Conflicting conditions in health matters].

PMID- 15957653
TI  - [Legal forms of cooperation among physicians].
AB  - Medical occupational rights introduced in the sixties have entitled physicians to
      cooperate with one another. This form of professional cooperation is subject to
      the general corporate law, the medical occupational law, and the panel-doctor's
      right. The legal framework for the cooperation of physicians is provided by the
      federal law of the General Medical Council, the medical law in each German
      federal state, and the individual occupational ordinances of the single medical
      councils. These ordinances are essentially based on the pattern occupation
      ordinance approved during the Annual General Meeting of German Physicians
      (Deutsche Arztetag). This is regulated in the Federal German Code of Social Law
      Chapter V and in the panel-doctor's right (with approval of the physicians), and
      contains further ordinances regulating the legal cooperation of physicians. A
      novelty concerning the cooperation of physicians is the so-called "Medical Care
      Center", which has been introduced by law to reform the German health system. The
      Medical Care Center is a multidisciplinary institution that enables physicians to
      work as employees or as contracted physicians. For the set-up of a Medical Care
      Center all legal forms (including all kinds of legal entities) can be chosen.
      Some details of this recent change of law are in dispute.

PMID- 15957654
TI  - [Networking of medical activities from a medical standpoint].
AB  - The current healthcare system has reached its structural limits. The change of
      structures raises the expectation of improvements in quality and economic
      viability. The legal framework for such changes are given from the legislators
      within the GMG 2004. In view of the integrated medical care approach, the
      sectorally-organized care must convert in a care process without sectoral
      boundaries. To implement such models, professionally-led management associations
      are indispensable.

PMID- 15957655
TI  - [Legal aspects of networking of medical activities].
AB  - Medical networks lack a legal definition. From the viewpoint of social law, this
      term means a form of organization of joint-service providers in a non-specified
      composition for the undertaking of medical care activities; from the point of
      view of occupational law, this consists of a loose form of joint practice. Such
      medical network can conclude treatment contracts with the patients and exchange
      patients' medical records. A practice network can take over services as contract
      partner of hospitals or other institutions, in the interest of improved
      competition chances within the integrated care system. The joining of a third
      partner is basically left open by the MBO, however according to SGB V this is
      possible only after approval by all contract partners. In advance of a planned
      medical care center, is it recommended to found a physician network as starting
      model. Before single practices fuse into a single enterprise, management-, tax-,
      legal-, as well as psychological aspects must be considered.

PMID- 15957656
TI  - [Establishment of branch practices in the German healthcare system].
AB  - The physicians in the German out-patient healthcare system are normally bound to
      treat their patients in locally-registered practices. Exceptions to this
      commitment are external practice rooms and branch practices. For special
      services, a physician can run external rooms close to his practice. Branch
      practices, in contrast, have to be authorized by the regional physicians'
      association. The requisites in this respect are concretely defined (and partially
      increased) in a new regulation within the federal framework agreements. The
      authorization obligation applies also to the establishment of branch practices in
      medical care centers.

PMID- 15957657
TI  - [Telematics--a challenge for the medical occupational law].
AB  - Telematics offer new possibilities to all fields of medical activity. This has
      numerous legal implications. From the point of view of occupational law, the
      prohibition of remote treatment and the doctor-patient confidentiality are of
      particular interest. An analysis of paragraph 7 subparagraph 3 of the Physicians'
      Professional Ordinance (MBO) shows that the prohibition of remote treatment is no
      obstacle to applications of telemedicine, as long as there is at least one
      personal contact between a physician and the patient (including an adequate
      physical examination during a multistage treatment) and an assessment of remote
      treatment shows no medical shortcomings. Doctor-patient confidentiality and data
      protection law (section 9 MBO and section 203 StGB) safeguard the informational
      self-determination of the patient. Before transferring patient health data to a
      third party, the physician has to check whether an anonymous or pseudonymous
      transfer is possible. The transfer requires a preferably written consent of the
      patient. In case personal data transfer between physicians is necessary for
      medical purposes, the legal preconditions correspond to those of doctor-patient
      confidentiality. It is controversial in which cases the patient's consent has to
      be declared in written form. For documentation purposes, however, the written
      form is recommended. Transfer of patient data has to be effected using technical
      data protection means such as up-to-date encryption and electronic signatures.

PMID- 15957658
TI  - [New forms of medical profession--advertising].
AB  - Particularly in the last two years, the legislation of Part V of the German
      Social Code has challenged the time-honoured system of the physician's own
      medical practice as the panel doctor's registered office. New forms of outpatient
      care, for example the health centres, "Heilkunde-GmbHs", and the recently
      developed medical care centres, are intended to impact on patients' ambulatory
      healthcare. Due to the partial employee status of practice owners, and thus the
      relinquishing of the independent entrepreneurial structuring of their own
      practices, the construct of the traditional professional code of conduct for
      physicians is beginning to totter. It remains to be seen whether liberalisation
      of the model code of conduct will provide a remedy. The principle should,
      however, be adhered to that advertising in the physician sector must not be
      unethical, if we understand this to mean not strident, not confusing, and not
      comparative.

PMID- 15957659
TI  - [Cooperation between medical and non-medical personnel].
AB  - The reform of the healthcare system further eases the cooperation between doctors
      and non-medical personnel, as shown in this paper from the perspective of
      constitutional, occupational, and social law. From a constitutional point of
      view, it is notable how the federal legislation influences sectors of the medical
      occupational law that are traditionally in the domain of the German federal
      states. The occupational law allows medical-cooperation ventures in which
      possible professional partners are legally defined. Besides other admissibility
      requisites, it must remain possible for the physician to maintain his
      professional in dependence. Within the domains of social and medical law, the
      legislators develop, together with medical care centers and integrated medical
      care, further healthcare structures aimed at overcoming sectoral boundaries
      between different kinds of boundaries between different kinds of medical
      profession.

PMID- 15957660
TI  - [Demand for extramural funding in German hospitals].
AB  - Medical progress is based on scientific research and continuing medical education
      (CME). Because of the tight financial situation in German hospitals, however, it
      is becoming increasingly difficult to provide the monetary resources for research
      and education. Therefore, acquisition of extramural grants has become
      indispensable for German medical research. Nonetheless, time and again the
      medical professionals have to face public accusations of unlawful earnings
      through industry funds. Even though these accusations prove wrong in most cases,
      they harm the reputation of the medical profession. Thus, guidelines are needed
      that guarantee both the independence of medical decision making and a productive
      cooperation with industry sponsors. At their annual meeting in 2003, the elected
      representatives of the medical profession of Germany ("Deutscher Arztetag") have
      passed an amendment of the code of conduct for physicians concerning the
      cooperation of physicians and industry partners. The goal is to organize the
      cooperation in a way that the independence of the physicians remains
      unquestionable The following principles are now included in the code of conduct:
      Transparency of funding; separation of funding and decisions on buying medical
      products; equivalence of service and payment; and documentation of the
      cooperation within the framework of occupational law.

PMID- 15957661
TI  - [Extramural research granting: effects and side effects].
AB  - Extramural funding is an indispensable support of the dual financing system of
      research and innovative teaching, and its importance will certainly grow in the
      future. Although individually necessary, supported by the government, and legally
      regulated, extramural funding is associated to a number of possible conflicts
      that complicate its management. Well-defined rules in faculty administration
      (extramural grant ordinance) and unambiguous contracts are the best preposition
      for successful and undisturbed usage of extramural funding.

PMID- 15957662
TI  - [Extramural research funds and penal law--status of legislation].
AB  - After decades of smooth functioning, the cooperation of physicians and hospitals
      with the industry (much desired from the side of the government in the interest
      of clinical research) has fallen in legal discredit due to increasingly frequent
      criminal inquires and proceedings for unduly privileges, corruption, and
      embezzlement. The discredit is so severe that the industry funding for clinical
      research is diverted abroad to an increasing extent. The legal elements of
      embezzlement assume the intentional violation of the entrusted funds against the
      interest of the customer. Undue privileges occur when an official requests an
      advantage in exchange for a service (or is promised one or takes one) in his or
      somebody else's interest. The elements of corruption are then given when the
      receiver of the undue privilege provides an illegal service or takes a
      discretionary decision under the influence of the gratuity. The tension between
      the prohibition of undue privileges (as regulated by the penal law) and the
      granting of extramural funds (as regulated by the administrative law in academic
      institutions) can be reduced through a high degree of transparency and the start
      of control possibilities--public announcement and authorization by the officials-
      as well as through exact documentation and observance of the principles of
      separation of interests and moderation. With the anti-corruption law of 1997, it
      is possible to charge of corruption also physicians employed in private
      institutions. In contrast, physicians in private practice are not considered in
      the above criminal facts. They can only be charged of misdemeanor, or called to
      respond to the professional board, on the basis of the law that regulates
      advertising for medicinal products (Heilmittelwerbegesetz).

PMID- 15957663
TI  - [Legal aspects of medication prescription].
AB  - Legal directives concerning drug treatment prescription mainly focus on drug
      safety, conduct of clinical trials according to good clinical practice,
      foundation of drug therapy on solid evidence, and, in view of rapidly increasing
      drug expenditures, on control of costs spent on drugs by health insurance
      systems. Legal aspects of drug treatment are discussed in this paper, with
      emphasis on current interests such as pharmacovigilance and off-label drug use,
      as well as on primary duties of the physicians in charge of drug prescriptions.

PMID- 15957664
TI  - [Sponsoring of physicians in private practice].
AB  - The financing of advanced medical training for physicians by the pharmaceutical
      industry has been the subject of legal discussions for more than two decades.
      Recent legal changes have renewed the importance of industry sponsoring. At the
      106th national convention of the German physicians, the model ordinance for the
      German medical profession ("Musterberufsordnung fur die deutschen Arztinnen und
      Arzte-MBO-A") has been reformed, and for the first time individual physicians are
      now permitted, under certain circumstances, to receive financial support from
      sponsors to participate in medical-training events. A recent legal reform to
      modernize the healthcare system ("GKV-Modernisierungsgesetz"--GMG) obliges
      physicians to observe the law that regulates advertising of medicinal products
      ("Heilmittelwerbegesetz"--HWG); consequently, the physicians can commit a
      misdemeanor when accepting prohibited financial support. This essay discusses the
      implications of this legal reform for the most important types of commercially
      sponsored medical training. The GMG reform has introduced an obligation for
      physicians to absolve continuous medical training, however the resulting legal
      situation has not changed the requirement that this training remain free of
      commercial interests.

PMID- 15957665
TI  - [View of the industry].

PMID- 15957666
TI  - Unexpectedly high prevalence of alcohol use among pregnant Swedish women: failed
      detection by antenatal care and simple tools that improve detection.
AB  - OBJECTIVE: We examined the use of alcohol during early pregnancy in urban Swedish
      women, the ability of Swedish antenatal care to identify alcohol-related risk
      pregnancies and the utility of some potential tools for improving its
      performance. METHOD: Women attending regular antenatal care were randomized to
      regular assessment only (control, n = 156) or intensified screening
      (intervention, n = 147). In the intervention group, alcohol use was determined
      using the Timeline Followback (TLFB) interview, alcohol use habits with the
      Alcohol Use Disorder Inventory Test (AUDIT), and biomarkers for alcohol use were
      analyzed. Data were typically obtained in pregnancy week 12. RESULTS: In the
      intervention group as a whole, average absolute alcohol consumption during the
      first 6 weeks of pregnancy was low but highly variable (mean [SD] = 24.9 [50.5]
      g/week; 4.8 [6.0] episodes for the entire 6 week period); 22 women (15%) drank at
      levels exceeding 70 g/week during any 2 or more weeks and/or in a heavy episodic
      drinking pattern, 60 g/episode, on 2 or more episodes. The AUDIT had a moderate
      sensitivity (54%) to identify these subjects. Biomarkers identified subjects with
      somatic illness rather than high alcohol consumption. In the control group, only
      4 (3%) were identified as using alcohol, indicating a probable underestimation of
      alcohol use by regular antenatal screening procedures (p = .0001). CONCLUSIONS:
      An unexpected proportion of pregnant women in urban Sweden consume alcohol at
      levels likely to produce adverse effects. Regular antenatal care did not identify
      most of these risk pregnancies. The TLFB identified pregnant women with risk use
      of alcohol during pregnancy who were only partly identified by analyzing
      prepregnancy alcohol use patterns with the AUDIT. Elevated laboratory markers
      likely indicated somatic illness rather than harmful drinking.

PMID- 15957667
TI  - Assessing alcohol misuse during pregnancy: evaluating psychometric properties of
      the CAGE, T-ACE and TWEAK in a Brazilian setting.
AB  - OBJECTIVE: The present article evaluates the psychometric properties of the
      Portuguese-language versions of the CAGE, TWEAK and T-ACE questionnaires when
      used to identify alcohol misuse during pregnancy and compares these to historical
      data from the English-language versions. Also, construct validity of the
      Portuguese versions of those instruments was assessed. METHOD: Data were
      collected from March to September 2000 in three large public maternity wards in
      Rio de Janeiro, Brazil. Sample size varied according to the analysis. An intra
      observer reliability evaluation involved 95 replications carried out within a 24
      48 hour period. Kappa was used as an estimator. Cronbach's alpha coefficient,
      whether or not each item from the analysis was excluded, and the item-rest point
      biserial correlations addressed internal consistency (N = 786). For the appraisal
      of construct validity (n = 528), the relationship between alcohol misuse
      (evaluated by each instrument according to different cutoff points) and several
      putative underlying theoretically related dimensions (schooling, age, smoking,
      marital status, social support, illicit drug use, domestic violence and per
      capita household income) were evaluated. RESULTS: All kappas were above 0.70. The
      alpha coefficients for the Portuguese versions ranged from 0.48 to 0.68, a
      finding consistent with studies assessing the original instruments in English.
      Yet, irrespective of the instrument concerned a systematic increase was observed
      whenever the item on morning alcohol use ("Eye-opener") was removed from the
      analysis. Regarding construct validity, most tested hypotheses were corroborated,
      except for the CAGE using the cut-off point of 2. CONCLUSIONS: This study
      confirms other authors' findings that all but the aforementioned CAGE may be
      recommended to identify heavy alcohol use during pregnancy in general as well as
      in Portuguese-speaking populations in particular.

PMID- 15957668
TI  - Evaluation of a level of response to alcohol-based structural equation model in
      adolescents.
AB  - OBJECTIVE: A low level of response (LR) to alcohol relates to a family history of
      alcoholism and predicts future heavier drinking and alcohol-related problems. The
      current analyses evaluate how LR functions within the context of a Social
      Information Processing Model, using 238 subjects aged 13 to 19 years from the
      Collaborative Study on the Genetics of Alcoholism (COGA). METHOD: A structural
      equation model (SEM) was used to evaluate the relationship among (1) a family
      history (FH) of alcoholism, (2) the LR to alcohol, (3) expectations as measured
      by the Alcohol Expectancy Questionnaire and (4) the recent pattern of drinking
      among parents in the home as predictors of the maximum recent quantity of
      drinking, the maximum number of drinks ever consumed in 24 hours and the number
      of alcohol problems in the teenage subjects. RESULTS: When tested in the SEM, LR
      functioned as a mediator of the relationship between an FH of alcoholism and
      alcoholic outcome, and expectancy functioned as a partial mediator of the
      relationship between LR and outcome. Invariance testing revealed that the SEM
      performed similarly in light and heavy drinkers, the two sexes, and older versus
      young subjects. Both the measurement model and SEM had good characteristics of
      fit, and direct paths within the model explained 49% of the variance of outcome.
      CONCLUSIONS: Consistent with results from the San Diego Prospective Study, when
      tested in the more heterogeneous COGA population, LR functioned as a mediator of
      the relationship between the FH and alcoholic outcome. In these adolescents, LR
      not only had a direct relationship to alcoholic outcome but, in contrast to prior
      results in adults, also appeared to operate through expectations of the effects
      of alcohol in predicting heavier drinking and a higher rate of alcohol-related
      problems among teenagers.

PMID- 15957669
TI  - Psychosocial, cultural and genetic influences on alcohol use in Asian American
      youth.
AB  - OBJECTIVE: Environmental and cultural factors, as well as a genetic variant of
      the aldehyde dehydrogenase gene (the ALDH2*2 allele) have been identified as
      correlates of alcohol use among Asian Americans. However, concurrent examination
      of these variables has been rare. The present study assessed parental alcohol
      use, acculturation and ALDH2 gene status in relation to lifetime, current and
      heavy episodic drinking among Chinese and Korean American undergraduates. METHOD:
      Participants (N = 428, 51% women; 52% Chinese American, age 18-19 years) were
      first-year college students in a longitudinal study of substance use initiation
      and progression. Data were collected via structured interview and self-report,
      and participants provided a blood sample for genotyping at the ALDH2 locus.
      RESULTS: Gender, parental alcohol use and acculturation significantly predicted
      drinking behavior. However, none of the hypothesized moderating relationships
      were significant. In contrast with previous studies, ALDH2 gene status was not
      associated with alcohol use. CONCLUSIONS: Results indicate that although the
      variables examined influence alcohol use, moderating effects were not observed in
      the present sample of Asian American college students. Findings further suggest
      that the established association of ALDH2 status and drinking behavior in Asians
      may not be evident in late adolescence. It is possible that ALDH2 status is
      associated with alcohol consumption only following initiation and increased
      drinking experience.

PMID- 15957670
TI  - Associations of ALDH2 and ADH1B genotypes with response to alcohol in Asian
      Americans.
AB  - OBJECTIVE: Individuals with alcohol dependence are less likely to possess variant
      alleles of the alcohol-metabolizing genes, aldehyde dehydrogenase (ALDH2*2) and
      alcohol dehydrogenase (ADH1B*2), than non-alcohol-dependent controls. It is
      hypothesized that the mechanism through which these alleles protect against
      alcohol dependence is by causing elevations in acetaldehyde, which in turn cause
      an increased response to alcohol. Previous research has shown that individuals
      with ALDH2*2 demonstrate enhanced reactions to alcohol compared with those
      without this genetic variant, but evidence that ADH1B*2 is associated with a
      greater alcohol response is mixed. This study was designed to determine whether
      the ADH1B genotype is associated with more intense reactions to alcohol after
      controlling for the ALDH2 genotype. METHOD: Participants (N = 101) were Asian
      American college students. Each was evaluated using objective and subjective
      measures before and after ingestion of alcohol and placebo beverages. RESULTS:
      Participants with the ALDH2*1/*2 and ALDH2*2/*2 genotypes were more likely to
      experience vomiting following ingestion of the alcohol beverage than those with
      the ALDH2*1/*1 genotype. Participants with the ALDH2*1/*2 genotype also had
      greater pulse-rate increases, observed flushing ratings, and subjective feelings
      of intoxication 30 minutes after ingestion of alcohol than participants with the
      ALDH2*1/*1 genotype, despite equivalent blood alcohol concentration (BAC)
      measurements. Among participants with the ALDH2*1/*1 genotype, there were no
      additional effects of the ADH1B genotype on any measures of response to alcohol.
      Among participants with the ALDH2*1/*2 genotype, those with the ADH1B*2/*2
      genotype were more likely to experience alcohol-induced vomiting and to report
      feeling less "great overall" 30 minutes after ingestion of alcohol than those
      with the ADH1B*1/*2 genotype. CONCLUSIONS: These findings are consistent with the
      hypothesis that there is an additional effect of ADH1B*2 on level of response to
      alcohol, but only among individuals with the ALDH2*1/*2 genotype.

PMID- 15957671
TI  - Alcohol use and intimate partner violence as predictors of separation among U.S.
      couples: a longitudinal model.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship between
      partner violence (male-to-female and female-to-male) and heavy drinking
      (consuming five or more drinks per occasion) and the effect of this relationship
      on marital separation. METHOD: Married and cohabiting couples were selected
      through multistage random probability sampling from U.S. households. In 1995,
      1,635 couples were interviewed; 1,392 of these couples were re-interviewed in
      2000. The final analysis included couples who were still married or living with
      the same partner (intact n = 1,136) from the baseline, and couples who had broken
      up (nonintact n = 191) sometime during the 5-year follow-up period. RESULTS: The
      findings indicate that couples who reported female-perpetrated violence, female
      alcohol-related problems and male heavy-drinking episodes (one to three times a
      month) were 2.5-3 times more at risk for separation. On the other hand, female
      heavy drinking (one to three times a month) is less likely to predict separation.
      Cohabiting couples are also more at risk for separation than married couples.
      Couples with longer relationships are less at risk for separation. CONCLUSIONS:
      Marital counseling, therapy or intervention programs must address issues
      pertaining to partner violence and alcohol use among couples while concurrently
      providing information about healthy relationships and helping couples develop
      skills to attain them. The importance of preventing partner violence is
      increasingly recognized in the field of public health.

PMID- 15957672
TI  - Exploring bidirectional couple violence in a clinical sample of female
      alcoholics.
AB  - OBJECTIVE: Research suggests that high levels of dissatisfaction, conflict and
      aggression characterize the relationships of alcoholics. The present study
      addressed aspects of bidirectional violence that occur in the relationships of
      female alcoholics. METHOD: Participants were109 women (and their partners) in a
      randomized clinical trial comparing individual and couple treatment for female
      alcoholics. Participants completed the Modified Conflicts Tactics Scale (CTS);
      four CTS subscales were calculated: Verbal Aggression, Psychological Coercion,
      Minor Violence and Severe Violence. RESULTS: Sixty-one percent of the couples
      reported at least some violence (27% severe) between them in the prior year. In
      23% of the couples, the woman was more severely violent than the man; in 11% of
      the couples, the man was more severely violent. CONCLUSIONS: Overall, results
      suggest that verbal aggression, psychological coercion and physical violence
      occur in the context of a distressed relationship.

PMID- 15957673
TI  - Individual and partner predictors of recovery from alcohol-use disorder over a
      nine-year interval: findings from a community sample of alcoholic married men.
AB  - OBJECTIVE: Numerous studies have focused on the predictors of recovery in persons
      with alcohol use disorder (AUD). Most have been retrospective and have measured
      only predictors of short-term recovery after the completion of treatment. This
      prospective study evaluates the role of psychological and social factors in a
      community sample of both alcoholics and their partners in predicting recovery
      over a 9-year interval. METHOD: Alcoholic diagnostic status and life functioning
      of 134 community-recruited, initially coupled men meeting criteria for a 3-year
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AUD
      diagnosis at baseline were assessed over the 9-year period. Their partners also
      were assessed. Prediction involved comparing those who still had an AUD diagnosis
      at 9-year follow-up against those who no longer met AUD criteria. RESULTS:
      Predictors of recovery included number of experiences with treatment, education,
      number of years of intervening recovery over the follow-up period, partner
      baseline AUD status and partner's social support network. Alcoholics' initial
      severity of drinking did not predict long-term outcome. Furthermore, recovered
      men's partners decreased their AUD in the interim, whereas nonremitters' partners
      increased their AUD. The findings highlight the transitions in and out of AUD,
      with 62% of the men having stable drinking patterns of either remission or
      unremitting AUD diagnosis over the entire follow-up period. CONCLUSIONS: This
      study demonstrated the importance of interpersonal factors in maintaining AUD or
      promoting recovery. Consideration of partner characteristics and the marital
      context as factors in the recovery process is essential. Future research should
      examine the predictors of recovery in women, in adolescents and in racial groups
      other than white.

PMID- 15957674
TI  - Regional differences in alcohol use among U. S. military personnel.
AB  - OBJECTIVE: The purpose of this study was to examine differences in heavy alcohol
      use and alcohol-related negative effects among U.S. military personnel stationed
      in different world regions and to examine factors that may account for regional
      differences. METHOD: Data were drawn from the 1998 Department of Defense Survey
      of Health Related Behaviors among Military Personnel, which had a large
      representative sample of active-duty U.S. forces. Heavy alcohol use and related
      negative effects (severe consequences, productivity loss and alcohol overuse)
      were examined in four regions (Asia, Europe, Hawaii and continental United
      States; N = 17,154; 86% men) using multivariate logistic regression models that
      controlled for demographic factors. RESULTS: U.S. military personnel stationed in
      Asia were significantly more likely to be heavy alcohol users than personnel
      stationed in the other regions. Productivity loss was also significantly greater
      in Asia, whereas severe consequences and alcohol overuse were not. Possible
      explanations for the findings include local regional culture, availability of
      alcohol, freedom from restraints, response to stress, military culture and
      selection effects. CONCLUSIONS: Heavy alcohol use of military personnel varies by
      region of assignment and may be attributable to a variety of factors. Future
      studies need to examine regional alcohol use in greater detail and to include
      measures specific to potential explanatory domains to permit a more complete
      understanding of underlying causal mechanisms of heavy drinking by U.S. forces in
      Asia. Current findings suggest that alcohol use prevention and early intervention
      programs should be tailored to take account of regional differences.

PMID- 15957675
TI  - Effects of survey mode on self-reports of adult alcohol consumption: a comparison
      of mail, web and telephone approaches.
AB  - OBJECTIVE: Mail and Web surveys are two possible alternatives for reducing
      potential nonresponse bias in telephone-based studies of alcohol consumption.
      Mail surveys have been a staple of epidemiological research, but there is a
      dearth of similar research on Web surveys. Most studies using Web surveys have
      been conducted among college students or other specialized populations where
      Internet penetration is relatively high. The present study examines differences
      in self-reports of alcohol consumption among adult members of the general public
      surveyed by mail, Web and telephone. METHOD: Web and mail versions of the 2003
      Behavioral Risk Factor Surveillance System (BRFSS) instrument, traditionally a
      telephone-only survey, were developed and administered to address-matched
      households drawn from the random-digit dialed sampling frame used for the BRFSS.
      Comparisons were made with results from the ongoing telephone-based surveillance.
      RESULTS: A total of 4,051 interviews (836 mail, 1,143 Web, and 2,072 telephone)
      were completed with adults ages 18 or older in four U.S. states. The findings
      indicate considerable variation in the estimates for heavy drinking (five or more
      drinks on an occasion during the past 30 days) obtained across these modes and
      population subgroups, particularly among the Web respondents. CONCLUSIONS: Mail
      surveys appear to be a viable alternative to more traditional telephone surveys,
      whereas use of Web surveys with the general public appears more problematic. Both
      approaches, however, may complement telephone studies when used in mixed-mode
      designs. Because alcohol consumption is associated with a number of diseases,
      caution is required when using different modes of data collection in
      epidemiological studies.

PMID- 15957676
TI  - Psychiatric disorders among at-risk consumers of alcohol in the general
      population.
AB  - OBJECTIVE: At-risk consumption of alcohol has increasingly become the focus of
      primary and secondary prevention efforts. Little is known about the co-occurrence
      of psychiatric disorders with at-risk drinking. We examined patterns of
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV)
      lifetime co-occurrence of psychiatric disorders in individuals in the general
      population with at-risk consumption of alcohol, alcohol abuse, alcohol dependence
      and moderate drinking/abstention, considering potential gender differences.
      METHOD: Cross-sectional data of a representative general population-based study
      were analyzed. Based on DSM-IV criteria, participants aged 18-64 (N = 4,074;
      2,045 men) were diagnosed using a standardized computer-assisted version of the
      Munich Composite International Diagnostic Interview (M-CIDI). Nonpsychotic Axis-I
      lifetime diagnoses were examined. At-risk consumption of alcohol was defined as
      an average of more than 20 g (0.71 oz) pure alcohol consumption per day for women
      and 30 g (1.06 oz) for men, with alcohol abuse or alcohol dependence excluded.
      RESULTS: Almost 9% of participants were identified as at-risk drinkers.
      Prevalence rates for at-risk drinkers were 16.9% for affective, 18.1% for anxiety
      and 17.8% for somatoform disorders. Compared with moderate drinkers/abstainers,
      at-risk drinkers showed a twofold increased risk of having a psychiatric
      disorder. Subjects with alcohol abuse showed a comparable level of risk and
      individuals with alcohol dependence showed an even greater risk. Female at-risk
      drinkers were twice as likely to have a psychiatric disorder as their male
      counterparts. The odds ratios for psychiatric disorders in at-risk drinkers
      compared with moderate drinkers/abstainers, however, did not differ in men and
      women. CONCLUSIONS: Rates of psychiatric co-occurrence among at-risk drinkers
      were considerably elevated when compared with moderate drinkers/abstainers. These
      findings underline the relevance of at-risk consumption of alcohol and represent
      an important challenge to public health efforts regarding screening of
      psychiatric disorders and referral to appropriate treatment services.

PMID- 15957677
TI  - Persistent cognitive deficits in community-treated alcoholic men and women
      volunteering for research: limited contribution from psychiatric comorbidity.
AB  - OBJECTIVE: The contribution of psychiatric comorbidity to cognitive status was
      assessed in a sample of treatment-seeking alcoholics who met criteria to
      participate in studies of effects of chronic alcohol misuse on brain structure
      and cognition. METHOD: Alcoholic men (n = 43) and women (n = 21) who responded to
      notices about a research study were screened, clinically assessed and
      administered Wechsler Memory and Intelligence tests after 3 months of sobriety,
      on average. Cognitive performance was compared with that of an age-matched sample
      of healthy controls (n = 51). RESULTS: As a group, the alcoholics achieved
      significantly lower scores than controls on summary indices of the Wechsler
      Memory and Adult Intelligence Scales and showed greater decline from estimated
      premorbid intelligence levels than controls. Almost 60% of the alcoholics had at
      least one additional psychiatric (mood or anxiety) or past substance-dependence
      comorbidity. There were no marked sex differences in patterns of comorbidity.
      Comorbid alcoholics were younger, had consumed less alcohol over their lifetime
      and performed between noncomorbid alcoholics and controls on all tests.
      CONCLUSIONS: Mood and anxiety comorbidity did not necessarily compound poor
      cognitive test performance associated with chronic alcohol misuse. While
      unexpected, this finding suggests that, in this sample, poorer cognitive
      performance was more a function of alcoholism per se than nonalcoholic
      comorbidity.

PMID- 15957678
TI  - Racial/Ethnic differences in the association between college attendance and heavy
      alcohol use: a national study.
AB  - OBJECTIVE: This study examined racial/ethnic differences in the association
      between college attendance and heavy alcohol use and factors that may underlie
      this relationship. METHOD: Interview data collected from 12,993 young adults who
      participated in the National Longitudinal Study of Adolescent Health were
      analyzed to determine if 4- or 2-year college status is differentially associated
      with heavy alcohol use for five racial/ethnic groups (white, black, Hispanic,
      Asian, Other) and to assess the explanatory value of selected social and
      psychological factors. RESULTS: Four-year college status was positively
      associated with heavy alcohol use among white young adults but inversely related
      to heavy drinking among blacks and Asians. Two-year college status also was
      inversely associated with heavy drinking among blacks, Hispanics and Others.
      Among whites, the association between 4-year college attendance and heavy
      drinking was partially explained by living away from parents, friends' heavy
      drinking and time socializing with friends. Among blacks, the inverse
      relationship between college attendance and heavy alcohol use was partially
      explained by lower levels of friends' heavy drinking, depression and delinquency.
      Friends' heavy drinking also partially explained observed relationships between
      college attendance and heavy drinking among Asians and Others. CONCLUSIONS: Four
      year college attendance increases the likelihood of heavy alcohol use among white
      young adults but may decrease the likelihood of heavy drinking among blacks and
      Asians. Two-year college attendance also may reduce the risk for heavy drinking
      among blacks, Hispanics and young adults who are Native American or multi-ethnic.
      Social and psychological factors partly explain these relationships and also
      differ for racial/ethnic groups.

PMID- 15957679
TI  - Alcohol use in early adolescence: the effect of changes in risk taking, perceived
      harm and friends' alcohol use.
AB  - OBJECTIVE: Friends' substance use, sensation seeking and low perceived harm are
      well-established risk factors for substance use, but they are often treated as
      stable factors that affect adolescents' likelihood of substance use. This study
      instead explores the effects of changes in risk factors for individual
      adolescents. METHOD: Participants in this study were 1,065 male and female
      students. The students were in sixth or seventh grade at the initial survey and
      provided survey data on three additional occasions over a period of 2 years.
      Random-coefficient models were used to assess the intraindividual variability of
      friends' alcohol use, perceived harm, and risk taking and their effect on alcohol
      use. RESULTS: As expected, the overall number of alcohol-using friends is
      correlated with a student's own alcohol use. In addition, there is a dynamic
      relationship within student; as friends' alcohol use changes over time, it is
      accompanied by parallel changes in alcohol use by the individual. Two moderating
      variables of the effect of friends' use of alcohol were validated: perceived harm
      of alcohol use and risk taking. The effect of increased exposure to alcohol-using
      friends is more robust during times when an adolescent also has become less
      likely to perceive the harmful effects of alcohol use or when an adolescent
      indicates increased interest in risk-taking behavior. CONCLUSIONS: Although
      friends' use of alcohol is a salient predictor of an adolescent's own use of
      alcohol, some types of students are more likely than others to be influenced by
      friends' behavior, In particular, students' perception of harm and predisposition
      to risk taking are important moderators of the effect of friends' influence.

PMID- 15957680
TI  - A brief experimental alcohol beverage-tailored program for adolescents.
AB  - OBJECTIVE: The objective of this study was to develop and test a brief,
      experimental alcohol preventive intervention matched to the use of specific
      alcohol beverages among adolescents. METHOD: A total of 232 high school students
      who drank within the last year participated in this study. Participants were
      randomly assigned to either the experimental intervention or a minimal
      intervention control. Four-month postintervention data are reported. RESULTS:
      Overall multivariate analyses of covariance (MANCOVAs) were significant (p's <
      .05) on risk factors (influenceability, perceived severity, perceived
      susceptibility and perceived peer prevalence) for three of six beverages (beer,
      wine and distilled spirits), with a fourth, malt liquor, approaching significance
      (p = .06). These tests showed intervention adolescents experiencing less risk for
      alcohol use than control adolescents. In addition, whereas the overall MANCOVA
      for malt liquor use was not significant, univariate analyses were significant for
      30-day frequency (F = 5.69, 1/195 df, p = .01) and 30-day quantity of malt liquor
      use (F = 4.03, 1/195 df, p = .04) with intervention adolescents showing less
      consumption than control adolescents. A post hoc analysis examining differential
      intervention effects using preintervention drug use as a factor (i.e., 30-day
      cigarette or marijuana use) showed a significant overall factorial MANCOVA
      interaction (F = 6.90, 4/189 df, p = .000), with drug-using intervention
      adolescents consuming cigarettes and marijuana less frequently than drug-using
      control adolescents at postintervention. CONCLUSIONS: The findings of this study
      suggest the brief, beverage-tailored intervention reduced certain risk factors
      mediating individual alcohol beverage use and consumption of malt liquor (4
      months after intervention) and may have reduced the frequency of cigarette and
      marijuana use among those already using drugs.

PMID- 15957681
TI  - It's all fun and games...or is it? Collegiate sporting events and celebratory
      drinking.
AB  - OBJECTIVE: Heavy drinking is prevalent on college campuses, and collegiate
      sporting events may precipitate heavy drinking. Despite this, relatively few
      studies have examined student drinking on the days of sporting events. In 2003,
      Syracuse University won the men's National College Athletic Association
      basketball championship; ongoing data collection allowed an investigation of
      alcohol consumption at Syracuse University during the two Final Four game days,
      when the semifinals and championship games are played. The goals of the study
      were to examine the level of alcohol use on these days and to examine factors
      related to game-day consumption. METHOD: As a part of an ongoing study, 206
      undergraduate students completed several questionnaires, then returned daily
      drinking diaries at 1-week intervals for 4 consecutive weeks. RESULTS: Alcohol
      consumption levels on the two game days exceeded what is typical on campus.
      Further analyses conducted using zero-inflated negative binomial regression
      modeling demonstrated that heavier drinkers were more likely to drink alcohol,
      and drink alcohol heavily, on both game days. Furthermore, lack of impulse
      control was independently associated with an increased likelihood of drinking on
      both days. CONCLUSIONS: Although results from this study should be considered
      preliminary, these data document heavier drinking associated with high-profile
      athletic events. Sporting events may be a particularly opportune time and venue
      for collegiate risk-reduction programs.

PMID- 15957682
TI  - Psychobehavioral risk factors, substance treatment engagement and clinical
      outcomes as predictors of emergency department use and medical hospitalization.
AB  - OBJECTIVE: Prior research on health care utilization after treatment for
      substance misuse disorders has not accounted for posttreatment clinical outcomes
      as well as putative confounds associated with both substance use and health care.
      This study examined the association of posttreatment health care utilization with
      treatment factors (program type and time in treatment) and baseline
      psychological/behavioral risk factors (smoking status and level of depressive,
      alcohol and drug dependence symptoms). The study also examined whether
      posttreatment clinical outcomes-participation in aftercare, Alcoholic Anonymous
      (AA) attendance, substance use, depressive symptoms and smoking- were associated
      with subsequent health care utilization. METHOD: We analyzed predictors of
      posttreatment medical hospitalizations and emergency department (ED) use among
      15,041 participants in a multistate treatment evaluation project conducted from
      1987 to 1995. RESULTS: Greater time in treatment reduced the likelihood of future
      hospitalizations and ED use, whereas clients in outpatient treatment were less
      likely to be hospitalized. Baseline measures of depressive, alcohol and drug
      dependence symptoms were each independently associated with subsequent health
      care use. Posttreatment aftercare participation reduced the likelihood of future
      hospitalization and ED use, whereas AA attendance also reduced the likelihood of
      hospitalization. In addition, posttreatment counts of depressive symptoms
      increased the likelihood of future hospitalization and ED use. Substance relapse
      increased the likelihood of subsequent ED use. CONCLUSIONS: The study supports
      the public health importance of substance misuse disorders treatment, with
      greater treatment involvement associated with lower high-cost medical
      utilization. Treatment clinical outcomes-posttreatment relapse and depressive
      symptoms-partially mediate the effect of treatment on health care utilization.

PMID- 15957683
TI  - Diagnostic usefulness of brief versions of Alcohol Use Disorders Identification
      Test (AUDIT) for detecting hazardous drinkers in primary care settings.
AB  - OBJECTIVE: The aim of this study was to evaluate the diagnostic usefulness of the
      brief versions of the Alcohol Use Disorders Identification Test (AUDIT) for
      detecting hazardous drinkers and to compare it with that of the full-AUDIT in
      primary care settings. METHOD: Five hundred patients were randomly selected in a
      primary care center. An interview on quantity-frequency was administered for
      assessment of weekly alcohol intake. The standard used for classification of
      hazardous drinkers was a weekly alcohol consumption of 280 g for men and 168 g
      for women. Cut-off points were 8 for the full-AUDIT, 1 for the AUDIT-3 (third
      item), 3 for the AUDIT-C (items 1, 2 and 3), 5 for the AUDIT-PC (items 1, 2, 4, 5
      and 10) and 3 for the modified Fast Alcohol Screening Test (m-FAST; items 3, 5, 8
      and 10). Sensitivity, specificity, positive and negative predictive values, and
      areas under the receiver operating characteristic (AUROC) curves were measured.
      RESULTS: Diagnostic usefulness of the questionnaires for detecting hazardous
      drinkers was for the full- AUDIT: 81.4% sensitivity, 94.6% specificity and 0.97
      AUROC curve; for the AUDIT-3: 83.1% sensitivity, 90.9% specificity and 0.89 AUROC
      curve; for the AUDIT-C: 100% sensitivity, 79.4% specificity and 0.97 AUROC curve;
      for the AUDIT-PC: 98.3% sensitivity 90.9% specificity and 0.97 AUROC curve; and
      for the m-FAST: 79.7% sensitivity, 93.7% specificity and 0.93 AUROC curve.
      CONCLUSIONS: The AUDIT-C and AUDIT-PC show a higher sensitivity, lower
      specificity and a similar AUROC curve than the full-AUDIT, thus allowing their
      use as screening instruments that are as reliable as the original test for
      detecting hazardous drinkers. The AUDIT-3 and m-FAST, when compared with the full
      AUDIT, performed less well, therefore limiting their use for this purpose.

PMID- 15957684
TI  - Local anaesthesia--after xylocaine.

PMID- 15957685
TI  - Pneumonia in intensive care--another frontier?

PMID- 15957686
TI  - Fresh frozen plasma after brown snake bite--helpful or harmful?

PMID- 15957687
TI  - High-dose buprenorphine: perioperative precautions and management strategies.
AB  - Buprenorphine has been in clinical use in anaesthesia for several decades.
      Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser,
      Slough, U.K.) has been increasingly used as maintenance therapy in opioid
      dependence, as an alternative to methadone and other pharmacological therapies.
      Buprenorphine has unique pharmacological properties making it well suited for use
      as a maintenance therapy in opioid dependence. However, these same properties may
      cause difficulty in the perioperative management of pain. Buprenorphine is a
      partial opioid agonist, attenuating the effects of supplemental illicit or
      therapeutic opioid agonists. As a result of its high receptor affinity,
      supplemental opioids do not readily displace buprenorphine from the opioid
      receptor in standard doses. High-dose buprenorphine has an extended duration of
      action that prolongs both of these effects. The perioperative management of
      patients stabilized on high-dose buprenorphine and undergoing surgery requires
      consideration of the likely analgesic requirements. Where possible the
      buprenorphine should be continued. Pain management should focus on maximizing non
      opioid analgesia, local anaesthesia and non-pharmacological techniques. Where
      pain may not be adequately relieved by these methods, the addition of a full
      opioid agonist such as fentanyl or morphine at appropriate doses should be
      considered, accompanied by close monitoring in a high dependency unit. In
      situations where this regimen is unlikely to be effective, preoperative
      conversion to morphine or methadone may be an option. Where available, liaison
      with a hospital-based alcohol and drug service should always be considered.

PMID- 15957688
TI  - Assessment of outcome over a 10-year period of patients admitted to a
      multidisciplinary adult intensive care unit with haematological and solid
      tumours.
AB  - The risk factors for time to mortality, censored at 30 days, of patients admitted
      to an adult teaching hospital ICU with haematological and solid malignancies were
      assessed in a retrospective cohort study. Patients, demographics and daily ICU
      patient data, from admission to day 8, were identified from a prospective
      computerized database and casenote review in consecutive admissions to ICU with
      haematological and solid tumours over a 10-year period (1989-99). The cohort, 108
      ICU admissions in 89 patients was of mean age (+/-SD) 55+/-14 years; 43% were
      female. Patient diagnoses were leukaemia (35%), lymphoma (38%) and solid tumours
      (27%). Median time from hospital to ICU admission was five days (range 0-67). On
      ICU admission, 50% had septic shock and first day APACHE II score was 28+/-9.
      Forty-six per cent of patients were ventilated. ICU and 30-day mortality were 39%
      and 54% respectively. Multivariate Cox model predictors (P<0.05), using only ICU
      admission day data were: Charlson comorbidity index (CCI), time to ICU admission
      (days) and mechanical ventilation. For daily data (admission through day 8),
      predictors were: cohort effect (2nd vs 1st five-year period); CCI; time to ICU
      admission (days); APACHE II score and mechanical ventilation. Outcomes were
      considered appropriate for severity of illness and demonstrated improvement over
      time. Ventilation was an independent outcome determinant. Controlling for other
      factors, mortality has improved over time (1st vs 2nd five year period). Analysis
      restricted to admission data alone may be insensitive to particular covariate
      effects.

PMID- 15957689
TI  - The effect of adjunctive fresh frozen plasma administration on coagulation
      parameters and survival in a canine model of antivenom-treated brown snake
      envenoming.
AB  - This study aimed to assess the effects of dugite envenoming on blood coagulation
      and platelet count in a canine model, and the efficacy of fresh frozen plasma
      (FFP) in reversing the clotting disorder after both adequate and inadequate venom
      neutralization. Following initial dosing and administration studies, an
      intravenous venom dose of 1 microg/kg was administered to eleven dogs. This was
      followed 30 minutes later by antivenom in either adequate or inadequate doses. A
      further 30 minutes later, the animals were given either two units of their own
      FFP or saline. Fibrinogen, aPTT and platelet levels were monitored for eight
      hours. Of the six study dogs given antivenom plus FFP, two died at around 60 to
      90 minutes post envenoming, at the end of the FFP infusions, and all but one of
      the survivors had persistent afibrinogenaemia. Of the five study dogs given
      antivenom and no FFP, all but one had return of detectable fibrinogen at eight
      hours after envenoming. The platelet count fell in all animals with recovery
      independent of antivenom dose, administration of FFP, or regeneration of
      fibrinogen. Post mortem examinations of dogs that died during dosage and
      administration studies showed massive intracardiac clots. We conclude that early
      death from Brown Snake envenoming may be due to massive intravascular clotting.
      FFP administration was associated with persistent afibrinogenaemia regardless of
      antivenom dose. In the absence of any evidence for its efficacy, this study
      suggests that the role of FFP after Brown Snake envenoming should be
      reconsidered.

PMID- 15957690
TI  - Use of intrathecal neostigmine as an adjunct to other spinal medications in
      perioperative and peripartum analgesia: a meta-analysis.
AB  - Intrathecal neostigmine has been used as an adjunct to intrathecal local
      anaesthetic or opioid to prolong regional analgesia and improve haemodynamic
      stability, with variable results. This meta-analysis aims to evaluate the
      effectiveness and side-effects of intrathecal neostigmine in the perioperative
      and peripartum settings. The literature search was based on Cochrane Controlled
      Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases.
      Volunteer and animal studies were excluded. We identified 26 studies and 19 were
      considered suitable for detailed data extraction. Intrathecal neostigmine
      increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3;
      P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to
      5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to
      28.9; P=0.00001). It improved the overall 24 hour VAS score (-1.4 VAS pain score,
      95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue
      analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number
      of rescue injections of nonsteroidal anti-inflammatory drug within the first 24
      hours (-0.8, 95% CI: -1.1 to -0.4; P=0. 00001). It did not affect the duration of
      motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of
      ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal
      neostigmine to other spinal medications improves perioperative and peripartum
      analgesia marginally when compared with placebo. It is associated with
      significant side-effects and the disadvantages outweigh the minor improvement in
      analgesia achieved.

PMID- 15957691
TI  - The linearity of the visual analogue scale in patients with severe acute pain.
AB  - The visual analogue scale (VAS) is a standard measurement tool in pain research
      and clinical practice, and has been shown to have linear scale properties for
      mild to moderate pain. Our aim was to evaluate the scaling properties of the VAS
      in subjects with severe acute pain. After Ethics Committee approval we studied 22
      patients and asked them to rate the severity of their pain on a 100 mm VAS at the
      initial assessment (VAS1), and again after administration of analgesic
      medication. The subject was asked to nominate when they considered their pain
      intensity had halved, and at this time they were asked to rate this on a second
      VAS (VAS0.5). When the subject had received satisfactory relief of their pain,
      they were asked to describe how much their pain had been relieved and were then
      asked to rate their final pain state using a third VAS (VASfinal). The mean (SD)
      scores were VAS1 84 (14) (range 56-100), VAS0.5 42 (13) and VASfinal 21 (16). The
      mean (95% CI) for VASratio was 0.51 (0.45-0.57). The mean (SD) patients' estimate
      of pain relief was 77 (21)% from that of baseline, with a mean (SD) VASfinal 0.26
      (0.20), 95% CI 0.17-0.38. The correlation of the patients' estimate of pain
      relief with the VASfinal was r=0.89, rho=0.87, both P<0.001. The VAS is a linear
      scale in subjects with severe acute pain. Changes in the VAS score represent a
      relative change in the magnitude of pain sensation.

PMID- 15957692
TI  - A new technique to determine the size of double-lumen endobronchial tubes by the
      two perpendicularly measured bronchial diameters.
AB  - The cross-section of the mainstem bronchi is not completely round. For
      preoperative selection of a double-lumen endobronchial tube size, it may be
      necessary to measure the mediolateral and the anteroposterior bronchial
      diameters, which can be measured respectively on chest radiograph and computed
      tomography. With Internal Review Board approval and patients' informed consent,
      105 elective thoracic surgical patients who needed left-sided double-lumen tubes
      were enrolled. Double-lumen tube size was selected depending on the arithmetic
      mean of the mediolateral and anteroposterior bronchial diameters. Moreover, the
      outer diameters of the bronchial tube should be smaller than both mediolateral
      and anteroposterior diameters. The recommended bronchial diameter for each double
      lumen tube size was chosen so that the mean of the two bronchial diameters was 0
      to 2.0 mm larger than the upper limit of 95% confidence interval of the averaged
      outer diameter of the bronchial tube of the selected double-lumen tube. In no
      case was the predicted double-lumen tube size inappropriate. Generally,
      anteroposterior bronchial diameters appeared to be different from mediolateral
      diameters (P=0.001). The double-lumen tube size to be selected based on only one
      bronchial diameter was different from the one selected based on two
      perpendicularly measured bronchial diameters in 54.3% of patients (57/105).
      Preoperative selection of the double-lumen tube size based on the
      anteroposterior, mediolateral and mean bronchial diameters seems to be useful in
      that this may obviate the need to change an inappropriately sized double-lumen
      tube and may be helpful in reducing the related complications.

PMID- 15957693
TI  - Spinal-induced hypotension in elderly patients with hip fracture. A comparison of
      glucose-free bupivacaine with glucose-free bupivacaine and fentanyl.
AB  - Intraoperative hypotension is a common and potentially deleterious event in
      elderly patients undergoing spinal anaesthesia for repair of hip fractures. The
      synergism between intrathecal opioids and local anaesthetics may allow a
      reduction in the dose of local anaesthetic and cause less sympathetic block and
      hypotension, while still maintaining adequate anaesthesia. We studied 40 elderly
      patients having either an insertion of a dynamic hip screw or a hemiarthroplasty
      and compared 9.0 mg glucose-free bupivacaine with added fentanyl 20 microg (group
      BF) with 11.0 m glucose-free bupivacaine alone (group B). Hypotension was defined
      as a fall in systolic blood pressure to less than 75% baseline or less than 90
      mmHg. The incidence and frequency of hypotension in group BF were less than in
      group B. Similarly, falls in systolic, diastolic and mean blood pressures were
      all less in group BF than in group B. However, there were four failed blocks in
      group BF and one in group B.

PMID- 15957694
TI  - Growth of Staphylococcus epidermidis in anaesthetic resuscitative drugs:
      implications for potential contamination.
AB  - This controlled laboratory study investigated the survival of Staphylococcus
      epidermidis (S. epidermidis) over a 24 hour period in four commonly drawn-up
      anaesthetic resuscitative drugs: suxamethonium, atropine, metaraminol and
      ephedrine. These drugs were prepared in typical therapeutic concentrations and
      then inoculated with S. epidermidis. Samples of the inoculated drug preparations
      were cultured on horse blood agar plates at 0, 2, 6, 12 and 24 hourly intervals
      and incubated for 24 hours. Colony counts were performed at the end of the
      incubation period. Suxamethonium, atropine and metaraminol all showed an
      inhibitory effect on colony counts within the first six hours. There was a more
      gradual decline of colony counts over a 24 hour period in the ephedrine solution.
      This decline was similar to that occurring in the normal saline. It is concluded
      that suxamethonium, atropine and metaraminol do not support the survival of the
      common skin contaminant, S. epidermidis over a 24 hour period.

PMID- 15957695
TI  - Patient-controlled sedation using remifentanil for third molar extraction.
AB  - The purpose for this study was to examine the efficacy of patient-controlled
      sedation (PCS) with remifentanil as an intravenous adjunct to local anaesthesia
      for treating pain associated with dental extraction during monitored anaesthetic
      care. Forty ASA 1-2 and aged 18 or older Chinese patients presenting for third
      molar extraction on an outpatient basis were randomly assigned to either
      remifentanil (RG; n =20) or saline groups (CG; n =20). All patients completed the
      study. Patients in the RG and CG were comparable in terms of demographic
      variables, PCS demands and PCS boluses. There was high variability of PCS among
      patients in both groups in terms of demands (range for RG 0-62; CG 0-41) and
      consumption (range for RG 0-26; CG 0-13). Neither group required any rescue local
      anaesthetic injection for pain or midazolam for anxiety. There was no clinically
      relevant differences in outcome measures (pain scores, anxiety scores, systolic
      and diastolic blood pressures, heart rate, and SpO2) between the two groups.
      There were no other major complications such as apnoea, desaturation,
      bradycardia, or chest wall rigidity in either group. We conclude that, although
      it appeared to be safe, the addition of patient-controlled remifentanil was not a
      useful adjunct to local anaesthesia for pain associated with third molar dental
      extraction.

PMID- 15957696
TI  - Biologically active contaminants of intravenous saline in PVC packaging:
      Australasian, European, and North American samples.
AB  - We have previously found evidence of contaminants in 0.9% saline packaged in
      polyvinyl chloride (PVC) for clinical use. For this current study we asked two
      questions: (1) what are the organic chemical contaminants in solutions packaged
      in PVC? and (2) do the contaminants vary in bags manufactured in different
      countries? We studied samples of 0.9% saline packaged in PVC from Australasia,
      Europe, and North America. We analysed the saline solutions with high-resolution
      capillary gas chromatography - mass spectrometry. Components of the Australasian
      and European bags were also analysed using thermodesorption followed by gas
      chromatography and mass spectrometry. In three pairs of samples we found twenty
      four different organic contaminants of the saline solutions. Diethylhexyl
      phthalate (DEHP) was found in all solutions; the concentrations were greater than
      10 microg/l in the Australasian and European samples. All samples contained 2
      ethyl hexanol (>50 microg/l), a DEHP breakdown product. The Australasian and
      North American samples contained cyclohexanone at concentrations of about 1000
      microg/l. The cyclohexanone probably originated in joints at the bases of the
      bags. Both the Australasian and European bags contained t-butyl cyclohexanol
      (>500 microg/l) and t-butyl cyclohexanone (>50 microg/l). Printing ink on the
      outside of the bags was the most likely source for both of these contaminants.
      Several of the contaminants are toxic to animals. Little is known about the
      toxicity of combinations of contaminants.

PMID- 15957697
TI  - The influence of the Univent endotracheal tube on internal jugular vein
      cannulation.
AB  - This prospective clinical investigation assessed the effect of placement of a
      Univent tube on the anatomy of the internal jugular veins and the success of
      cannulation of the left internal jugular vein. After obtaining informed consent,
      48 adult patients were enrolled. Of these, 42 patients were eligible and were
      divided into two groups: Univent tube (group U, n=21) and wire enforced
      endotracheal tube (group C, n=21). The Univent tube group were having a left
      thoracotomy. Using horizontal ultrasound scans just above the thyroid gland, the
      internal jugular vein was visualized and measured before and after Univent
      placement. The number of needle passes necessary to cannulate the left internal
      jugular vein in the two groups was also compared. Univent tubes were associated
      with lateral displacement of the right carotid artery and internal jugular vein
      on the convex side of the Univent tube, with compression of the right internal
      jugular vein by the artery, resulting in a kidney-shaped cross-section of the
      vein. On the left (concave side of the tube), the neck was indented, the sheath
      of the left carotid artery was displaced medially, and the left internal jugular
      vein distorted to an ellipse. There was a significant increase in the lateral
      diameter and a decrease in the cross-sectional area of the left internal jugular
      vein (t-test, P < 0.05). The first attempt at cannulation of the left internal
      jugular vein failed significantly more often in the Univent group (13/21 vs 5/21
      in group C, Chi-square 6.22, P=0.025). Cannulation of the internal jugular vein
      before placement of the Univent tube, or placement with ultrasound guidance is
      suggested.

PMID- 15957698
TI  - The spectrum of practice in the diagnosis and management of pneumonia in patients
      requiring mechanical ventilation. Australian and New Zealand practice in
      intensive care (ANZPIC II).
AB  - This study of ventilated patients investigated current clinical practice in 476
      episodes of pneumonia (48% community-acquired pneumonia, 24% hospital-acquired
      pneumonia, 28% ventilator-associated pneumonia) using a prospective survey in 14
      intensive care units (ICUs) within Australia and New Zealand. Diagnostic methods
      and confidence, disease severity, microbiology and antibiotic use were assessed.
      All pneumonia types had similar mortality (community-acquired pneumonia 33%,
      hospital-acquired pneumonia 37% and ventilator-associated pneumonia 24%, P=0.15)
      with no inter-hospital differences (P=0.08-0.91). Bronchoscopy was performed in
      26%, its use predicted by admission hospital (one tertiary: OR 9.98, CI 95% 5.11
      19.49, P< 0.001; one regional: OR 6.29, CI 95% 3.24-12.20, P<0.001), clinical
      signs of consolidation (OR 3.72, CI 95% 2.09-6.62, P<0.001) and diagnostic
      confidence (OR 2.19, CI 95% 1.29-3.72, P=0.004). Bronchoscopy did not predict
      outcome (P=0.11) or appropriate antibiotic selection (P=0.69). Inappropriate
      antibiotic prescription was similar for all pneumonia types (11-13%, P=0.12) and
      hospitals (0-16%, P=0.25). Blood cultures were taken in 51% of cases. For
      community-acquired pneumonia, 70% received a third generation cephalosporin and
      65% a macrolide. Third generation cephalosporins were less frequently used for
      mild infections (OR 0.38, CI 95% 0.16-0.90, P=0.03), hospital-acquired pneumonia
      (OR 0.40, CI 95% 0.23-0.72, P<0.01), ventilator-associated pneumonia (OR 0.04, CI
      95% 0.02-0.13, P<0.001), suspected aspiration (OR 0.20, CI 95% 0.04-0.92,
      P=0.04), in one regional (OR 0.26, CI95% 0.07-0.97, P=0.05) and one tertiary
      hospital (OR 0.14, CI 95% 0.03-0. 73, P=0.02) but were more commonly used in
      older patients (OR 1.02, CI 95% 1.01-1.03, P=0.01). There is practice variability
      in bronchoscopy and antibiotic use for pneumonia in Australian and New Zealand
      ICUs without significant impact on patient outcome, as the prevalence of
      inappropriate antibiotic prescription is low. There are opportunities for
      improving microbiological diagnostic work-up for isolation of aetiological
      pathogens.

PMID- 15957699
TI  - Disease risk and mortality prediction in intensive care patients with pneumonia.
      Australian and New Zealand practice in intensive care (ANZPIC II).
AB  - This study of ventilated patients investigated pneumonia risk factors and outcome
      predictors in 476 episodes of pneumonia (48% community-acquired pneumonia, 24%
      hospital-acquired pneumonia, 28% ventilator-associated pneumonia) using a
      prospective survey in 14 intensive care units within Australia and New Zealand.
      For community acquired pneumonia, mortality increased with immunosuppression (OR
      5.32, CI 95% 1.58-1799, P<0.01), clinical signs of consolidation (OR 2.43, CI 95%
      1.09-5.44, P=0.03) and Sepsis-Related Organ Failure Assessment (SOFA) scores (OR
      1.19, CI 95% 1.08-1.30, P<0.001) but improved if appropriate antibiotic changes
      were made within three days of intensive care unit admission (OR 0.42, CI 95%
      0.20-0.86, P=0.02). For hospital-acquired pneumonia, immunosuppression (OR 6.98,
      CI 95% 1.16-42.2, P=0.03) and non-metastatic cancer (OR 3.78, CI 95% 1.20-11.93,
      P=0.02) were the principal mortality predictors. Alcoholism (OR 7.80, CI 95% 1.20
      17.50, P<0.001), high SOFA scores (OR 1.44, CI 95% 1.20-1.75, P=0.001) and the
      isolation of "high risk" organisms including Pseudomonas aeruginosa,
      Acinetobacter spp, Stenotrophomonas spp and methicillin resistant Staphylococcus
      aureus (OR 4.79, CI 95% 1.43-16.03, P=0.01), were associated with increased
      mortality in ventilator-associated pneumonia. The use of non-invasive ventilation
      was independently protective against mortality for patients with community
      acquired and hospital-acquired pneumonia (OR 0.35, CI 95% 0.18-0.68, P=0.002).
      Mortality was similar for patients requiring both invasive and non-invasive
      ventilation and non-invasive ventilation alone (21% compared with 20%
      respectively, P=0.56). Pneumonia risks and mortality predictors in Australian and
      New Zealand ICUs vary with pneumonia type. A history of alcoholism is a major
      risk factor for mortality in ventilator-associated pneumonia, greater in
      magnitude than the mortality effect of immunosuppression in hospital-acquired
      pneumonia or community-acquired pneumonia. Non-invasive ventilation is associated
      with reduced ICU mortality. Clinical signs of consolidation worsen, while
      rationalising antibiotic therapy within three days of ICU admission improves
      mortality for community-acquired pneumonia patients.

PMID- 15957700
TI  - Predictors of physician confidence to diagnose pneumonia and determine illness
      severity in ventilated patients. Australian and New Zealand practice in intensive
      care (ANZPIC II).
AB  - The manner in which elements of clinical history, physical examination and
      investigations influence subjectively assessed illness severity and outcome
      prediction is poorly understood. This study investigates the relationship between
      clinician and objectively assessed illness severity and the factors influencing
      clinician's diagnostic confidence and illness severity rating for ventilated
      patients with suspected pneumonia in the intensive care unit (ICU). A prospective
      study of fourteen ICUs included all ventilated admissions with a clinical
      diagnosis of pneumonia. Data collection included pneumonia type - community
      acquired (CAP), hospital-acquired (HAP) and ventilator-associated (VAP),
      clinician determined illness severity (CDIS), diagnostic methods, clinical
      diagnostic confidence (CDC), microbiological isolates and antibiotic use. For 476
      episodes of pneumonia (48% CAP, 24% HAP, 28% VAP), CDC was greatest for CAP (64%
      CAP, 50% HAP and 49% VAP, P<0.01) or when pneumonia was considered "life
      threatening" (84% high CDC, 13% medium CDC and 3% low CDC, P<0. 001). "Life
      threatening" pneumonia was predicted by worsening gas exchange (OR 4.8, CI 95%
      2.3-10.2, P<0.001), clinical signs of consolidation (OR 2.0, CI 95% 1.2-3.2,
      P<0.01) and the Sepsis-Related Organ Failure Assessment (SOFA) Score (OR 1.1, CI
      95% 1.1-1.2, P<0.001). Diagnostic confidence increased with CDIS (OR 16.3, CI 95%
      8.4-31.4, P<0.001), definite pathogen isolation (OR 3.3, CI 95% 2.0-5.6) and
      clinical signs of consolidation (OR 2.1, CI 95% 1.3-3.3, P=0.001). Although the
      CDIS, SOFA Score and the Simplified Acute Physiologic Score (SAPS II) were all
      associated with mortality, the SAPS II Score was the best predictor of mortality
      (P = 0. 02). Diagnostic confidence for pneumonia is moderate but increases with
      more classical presentations. A small set of clinical parameters influence
      subjective assessment. Objective assessment using SAPS II Scoring is a better
      predictor of mortality.

PMID- 15957701
TI  - Treatment of polypharmacy overdose with multimodality extracorporeal life
      support.
AB  - A 45-year-old woman presented to the emergency department of a tertiary referral
      hospital after taking an overdose of verapamil, doxepin, quetiapine, diazepam,
      temazepam, and clonazepam. She rapidly developed shock refractory to
      pharmacological support and was placed on percutaneous venoarterial
      extracorporeal membrane oxygenation (ECMO). She had a severe metabolic acidosis
      from a combination of shock and drug intoxication that improved with continuous
      venovenous haemodialysis. Forty-eight hours after presentation, while still on
      ECMO, the patient had complete cardiac standstill for three and a half hours,
      attributable to slow-release verapamil, that resolved after the commencement of
      plasmapheresis. The role of plasmapheresis in verapamil overdose requires further
      study.

PMID- 15957702
TI  - Transfusion-related acute lung injury (TRALI).
AB  - A 50-year-old male presented for a Whipple's procedure to excise a pancreatic
      lesion. Massive transfusion of packed cells and fresh frozen plasma was required.
      Towards the end of the procedure, the patient developed sudden onset of frank
      pulmonary oedema and hypotension. A presumptive diagnosis of transfusion related
      lung injury was made after prompt investigations excluded circulatory overload or
      cardiogenic shock as the cause. This case report describes an increasingly common
      and life-threatening sequela of blood product transfusion, the management of
      which is complicated by the current lack of specific diagnostic tests.

PMID- 15957703
TI  - Unexpectedly high block following epidural catheter placement under direct
      vision: a case report.
AB  - A 72-year-old female underwent elective lumbar spinal decompression. At the end
      of the procedure an epidural catheter was sited by the surgeon under direct
      vision. A bolus of levobupivacaine was injected. Shortly after reaching the
      recovery area, the patient collapsed and required re-intubation and mechanical
      ventilation. She was extubated five hours later and suffered no adverse sequelae.
      Having excluded other possible causes of immediate post-operative collapse, a
      clinical diagnosis of subdural blockade was made. A literature search using
      Medline has found no other case reports of such a complication following epidural
      placement under direct vision.

PMID- 15957704
TI  - Anaesthetic considerations in Castleman's disease.
AB  - Castleman's disease is a lymphoreticular disorder, often localized and clinically
      silent. Systemic manifestations may occur. Castleman's disease may be associated
      with pathologies such as POEMS syndrome (polyneuropathy, organomegaly,
      endocrinopathy, monoclonal gammopathy, and skin changes), AIDS, amyloidosis,
      pemphigus vulgaris, and other types of cancer such as lymphoma and Kaposi's
      sarcoma. Careful preoperative evaluation is required to determine whether
      associated mediastinal or spinal canal masses or haematological disorders are
      present. The significance of these pathologies for anaesthetic management is
      discussed. We present the case of a 27-year-old female patient with Castleman's
      disease (hyaline-vascular variant) requiring vaginal reconstruction due to
      recurrent sores and synechiae.

PMID- 15957705
TI  - A problem with a PCA pump handset.

PMID- 15957706
TI  - Intensive insulin therapy and the bath insulin protocol.

PMID- 15957707
TI  - Accidental transection of radial [correction of radical] artery cannula.

PMID- 15957708
TI  - Another case of anaphylaxis and fibrinolysis.

PMID- 15957709
TI  - Pharmacoeconomic viewpoints on volatile anaesthesia--"much ado about nothing?".

PMID- 15957710
TI  - The use of the laryngeal mask in gynaecological laparoscopy.

PMID- 15957711
TI  - Local anaesthesia after cocaine.

PMID- 15957712
TI  - A review of the risks and benefits of nitrous oxide in current anaesthetic
      practice.

PMID- 15957713
TI  - Preoperative use of herbal medicines and vitamin supplements.
AB  - There has been a definite increase in the popularity and use of complementary and
      alternative medicines, including herbal medicines, in the last ten years. The aim
      of this study was to determine the prevalence and patterns of use of herbal
      medicines and vitamin supplements by patients in the preoperative period. A
      questionnaire was offered to all patients attending the pre-admission clinics at
      St. Vincent's Hospital and Box Hill Hospital, Melbourne, over an eight-month
      period in 2002. In all, 1102 questionnaires were completed (91.8% response rate).
      The prevalence of herbal medicine use was 14.3%, with an average user age of 54.0
      years and 61.4% female predominance. The five most popular herbs were Garlic,
      Evening Primrose, Gingko, St. John's Wort and Echinacea. The commonest reasons
      for herbal medicine use were acute and chronic medical conditions. 63.2% of
      patients had self-prescribed. 27.8% of herbal remedy users had informed the
      hospital doctors and 41.8% had notified their general practitioner The prevalence
      of vitamin supplement use was 20.4%, with an average user age of 54.8 years and
      66.2% female predominance. The five most popular vitamins were multivitamins,
      followed by vitamin B, C, E and D. The commonest reasons for vitamin use were
      maintenance of general well-being and health. The use of herbal medicines and
      vitamin supplements preoperatively by patients is common. Clinicians should
      endeavour to familiarize themselves with the more popular and significant herbal
      medications and, as part of the routine preoperative assessment, ask all their
      patients about their consumption of herbal remedies.

PMID- 15957714
TI  - Anatomy and anaesthesia of the lumbar somatic plexus.
AB  - Cadaveric dissection demonstrated the lumbar plexus to lie within the substance
      of psoas major, with the major branches of the lumbar plexus emerging into the
      psoas compartment adjacent to the L5 vertebra. Within psoas major, the lateral
      femoral cutaneous and femoral nerves were separated from the obturator nerve by a
      muscular fold in 36 of 60 plexuses. Anatomical variations were common, with the
      accessory obturator nerve being identified in 12 per cent of plexuses. All
      previously described lumbar plexus block approaches positioned the needle within
      close proximity to the lumbar plexus. Modifications to these approaches may
      increase efficacy and reduce complication rates.

PMID- 15957715
TI  - Messenger RNA expression of multiple immune mediators in leukocytes from elective
      orthopaedic surgical patients.
AB  - The aim of this longitudinal observational study was to investigate and describe
      the spectrum of messenger ribonucleic acid (mRNA) expression of multiple
      inflammatory markers in circulating leukocytes after major orthopaedic surgery.
      We studied ten elective arthroplasty patients perioperatively on the orthopaedic
      ward, and eight healthy volunteers for a comparison group. Venous blood specimens
      were collected preoperatively, and 6, and 24 hours postoperatively, together with
      6- and 24-hour postoperative wound drain specimens. The mRNA of 21 different
      inflammatory mediators was measured by real-time reverse transcriptase Polymerase
      Chain Reaction. Comparisons were made with the venous blood of eight healthy
      comparison subjects. There were significant differences (P<0.01) between
      preoperative specimens and normal comparisons (i.e. higher MPO, PDGF, TREM and
      IRAKM; lower mtHSP) reflecting the effects of chronic inflammation associated
      with osteoarthritis. There were significant increases (P<0.01) in expression of
      IL-8, MPO, IL-1beta, TREM, MMP9, and C5aR in circulating blood at 24 hours
      postoperatively, but not at six hours. There was no significant decrease in
      expression of any inflammatory mediator. There was no statistical difference in
      inflammatory mediator expression between drain specimens and venous specimens
      taken at the same time. We conclude that, in uncomplicated orthopaedic surgical
      patients, there was up-regulation of some cytokine mRNAs at both the local and
      systemic levels during the first day after surgery. We observed no evidence of
      immune compartmentalization, and found no evidence for innate immune paresis
      within the first day after surgery.

PMID- 15957716
TI  - Correlation between extravascular lung water and oxygenation in ALI/ARDS patients
      in septic shock: possible role in the development of atelectasis?
AB  - This study aimed to evaluate the relationship between PaO2/FiO2 ratio and
      extravascular lung water in septic shock-induced acute respiratory distress
      syndrome in a prospective observational clinical trial. Twenty-three patients
      suffering from sepsis induced acute respiratory distress syndrome were recruited.
      All patients were ventilated in pressure control/support mode. Haemodynamic
      parameters were determined by arterial thermodilution (PiCCO) eight hourly for 72
      hours. At the same time blood gas analyses were done and respiratory parameters
      were also recorded. Data are presented as mean +/-SD. For statistical analysis
      Pearson's correlation test, and analysis of variance (ANOVA) was used
      respectively. Significant negative correlation was found between extravascular
      lung water and PaO2/FiO2 (r = -0.355, P < 0.001), and significant positive
      correlation was shown between extravascular lung water and PEEP (r=0.557,
      P<0.001). A post-hoc analysis was performed when "low" PEEP: < 10 cmH2O and
      "high" PEEP: (10 cmH2O PEEP was applied, and neither the oxygenation, nor the
      driving pressure or the PaCO2 differed significantly, but the extravascular lung
      water showed significant difference when "high" or "low" PEEP was applied (13+/-5
      vs 9+/-2 ml/kg respectively, P=0.001). This study found significant negative
      correlation between extravascular lung water and PaO2/FiO2. The mechanism by
      which extravascular lung water affects oxygenation is unknown but the significant
      positive correlation between PEEP and extravascular lung water shown in this
      trial suggests that the latter may have a role in the development of alveolar
      atelectasis.

PMID- 15957717
TI  - The correlation between airborne methicillin-resistant Staphylococcus aureus with
      the presence of MRSA colonized patients in a general intensive care unit.
AB  - Air sampling directly onto a methicillin-resistant Staphylococcus aureus (MRSA)
      selective agar was performed at six locations three times weekly over a period of
      32 weeks in a new, initially MRSA-free Intensive Care Unit to examine if MRSA is
      present in air sample cultures and, if so, whether it is affected by the number
      of MRSA colonized patients present. A total of 480 air samples were collected on
      80 days. A total of 39/480 (8.1%) samples were found to be MRSA positive of which
      24/160 (15%) positive air samples were from the single rooms, where MRSA
      colonised patients were isolated, and 15/320 (4.7%) were from the open bed areas.
      A significant correlation was found between the daily number of MRSA colonized or
      infected patients in the Unit and the daily number of MRSA positive air samples
      cultures obtained (r2=0.128; P<0.005). The frequency of positive cultures was
      significantly higher in the single rooms than in the open bed areas (relative
      risk=3.2; P<0.001). The results from one of the single rooms showed a strong
      correlation between the presence of MRSA patients and MRSA positive air samples
      (relative risk=11.4; P<0. 005). Our findings demonstrate that the presence of
      airborne MRSA in our unit is strongly related to the presence and number of MRSA
      colonized or infected patients in the Unit.

PMID- 15957718
TI  - A comparison of the effects of prolonged (>10 hour) low-flow sevoflurane, high
      flow sevoflurane, and low-flow isoflurane anaesthesia on hepatorenal function in
      orthopaedic patients.
AB  - This study compared the effects of low-flow sevoflurane, high-flow sevoflurane
      and low-flow isoflurane on hepatorenal function during and after more than 10
      hours of anaesthesia. Twenty-five patients scheduled for elective orthopaedic
      surgery were categorized into three groups; low-flow sevoflurane (fresh gas flow
      at 1 litre/min, n = 9), high-flow sevoflurane (5 l/rmin, n = 7), or low-flow
      isoflurane (1 l/min, n=9). Inspiratory compoundA concentrations were measured.
      The groups had similar duration of anaesthesia and exposure to anaesthetic
      agents. The area under the curve of concentration (mean, SD) of compound A in the
      low-flow sevoflurane group (359.8, 106.1 ppm.h) was greater than that in the high
      flow sevoflurane group (61.1, 29.3 ppm.h; P<0.01). All groups showed normal
      plasma creatinine and creatinine clearance, and transient postoperative increases
      in plasma alanine aminotransferase and alpha glutathione-S-transferase, as well
      as urinary glucose and alpha glutathione-S-transferase, with no significant
      differences between groups. There were no significant relationships between the
      area under the curve of concentration of compound A and the biomarkers. These
      findings suggest that prolonged anaesthesia with low-flow sevoflurane has similar
      effects on hepatorenal function to prolonged anaesthesia with high-flow
      sevoflurane and low-flow isoflurane.

PMID- 15957719
TI  - The effect of haemodilution on antithrombin concentration during cardiac surgery.
AB  - The effect of haemodilution on antithrombin concentration was investigated in 73
      patients undergoing elective cardiac surgery with and without cardiopulmonary
      bypass. In patients who required cardiopulmonary bypass (n = 45), the
      antithrombin concentration fell to 52% of baseline during surgery (24.2 mg.dl(-1)
      to 12.6 mg.dl(-1)), and the haemoglobin level fell to 55% (136 g.l(-1) to 75 g.l(
      1)). In patients who did not require cardiopulmonary bypass (n = 28), the
      antithrombin concentration fell to 82% of baseline (23.7 mg.dl(-1) to 19.5 mg.dl(
      1)), and the haemoglobin concentration fell to 78% (141 g.l(-1) to 109 g.l(-1)).
      The overall correlation coefficient (r) for changes in antithrombin and
      haemoglobin concentrations was 0.76. The results indicate that most of the
      decrease in concentration of antithrombin during cardiac surgery is a consequence
      of cardiopulmonary bypass and is due to haemodilution. This data demonstrates
      that the percentage decrease in haemoglobin concentration can be used to estimate
      the percentage decrease in antithrombin concentration that occurs during cardiac
      surgery, if blood products that might effect the results are not administered
      between measurements.

PMID- 15957720
TI  - A comparison of open and laparoscopic approaches to adrenalectomy in patients
      with phaeochromocytoma.
AB  - We compared the perioperative profiles of patients undergoing unilateral
      phaeochromocytoma resection performed by open adrenalectomy with those performed
      by laparoscopic adrenalectomy. Data was collected prospectively on 24 patients
      (12 open, 12 laparoscopic). All patients underwent extensive preoperative medical
      preparation with phenoxybenzamine and beta-blockers. The final preoperative dose
      of phenoxybenzamine was similar in each group (laparoscopic 119+/-60 mg/day, open
      100+/-25 mg/day). Intraoperative haemodynamic instability was assessed by the
      requirement for therapeutic intervention. More haemodynamic instability was
      observed in the laparoscopic group but the differences were not statistically
      significant. Sodium nitroprusside use to treat hypertension (systolic blood
      pressure >180 mmHg) was more frequent and the duration of the infusions longer in
      the laparoscopic group; high dose beta-blocker therapy with atenolol and/or
      esmolol to treat intraoperative tachycardia (heart rate >90) was also more
      frequent in the laparoscopic group. The small sample size of the study limited
      the ability to detect a true difference. Blood loss was greater in the open
      adrenalectomy group but the difference was not significant. The operating time
      was significantly longer (236+/-78 vs 147+/-47 min, P<0.01) but the duration of
      postoperative hospitalization was significantly shorter (5+/-2 vs 11+/-4 days,
      P<0.01) in the laparoscopic group. Postoperative complications were not
      significantly different. There were no perioperative deaths. Overall, we observed
      more haemodynamic instability in patients undergoing laparoscopic resection but
      were unable to demonstrate a statistically significant difference. In our
      experience, laparoscopic adrenalectomy has the advantage of a shorter time to
      discharge from hospital.

PMID- 15957721
TI  - The type of carbon dioxide absorbent has no relation to the concentration of
      carbon monoxide in the breathing circuit during low-flow isoflurane anaesthesia
      in smoking and non-smoking subjects.
AB  - The present study was designed to investigate the concentrations of carbon
      monoxide (CO) in the anaesthetic circuit and of arterial carboxyhaemoglobin
      (COHb) during low-flow isoflurane anaesthesia in smoking and non-smoking subjects
      using three kinds of cardon dioxide (CO2) absorbent. Thirty smoking and 30 non
      smoking subjects were selected for this study, and these two groups were each
      divided into three groups according to the type of CO2 absorbent used (Wakolime
      A, Dragersorb Free, and Amsorb). Anaesthesia was maintained with 1.0% isoflurane
      and nitrous oxide (1. 0 l min(-1))/oxygen (1.0 l min(-1)). Concentrations of CO
      in the inspired breathing circuit and concentrations of arterial COHb were
      measured at 0, 1, 2, 3, and 4 hours after exposure to isoflurane. In the smoking
      groups there were no significant differences in CO concentrations in the circuit
      between the groups and the CO concentrations did not change significantly during
      the study period. There were also no significant differences in the arterial COHb
      values between the groups and the COHb concentrations remained constant. There
      was a significant linear correlation between the concentrations of CO and COHb
      (r=0.86, n =30, P<0.001). In the non-smoking groups all of the parameters
      remained constant at low levels that were independent of the type of CO2
      absorbents tested. The major source for increased intraoperative CO exposure is
      related to the patient's smoking status, and the type of CO2 absorbent used has
      no relation to an increase in CO concentration in the breathing circuit.

PMID- 15957722
TI  - Sevoflurane versus propofol for induction of anaesthesia for electroconvulsive
      therapy: a randomized crossover trial.
AB  - Propofol is often used to induce anaesthesia for electroconvulsive therapy. Some
      patients who receive propofol have fits of poor quality or inadequate duration
      despite increasing electroconvulsive therapy doses. Sevoflurane has been reported
      to exhibit pro-convulsant properties in some "at-risk" patients during
      anaesthesia for other procedures. The purpose of this study was to perform a
      randomized crossover trial in patients undergoing electroconvulsive therapy,
      comparing the effects on seizure parameters of propofol versus sevoflurane
      induction. Patients were randomly allocated to receive either sevoflurane or
      propofol for their first treatment. In the subsequent treatment the alternative
      agent was used. Patients in both treatment groups exhibited equally good fits,
      with those in the sevoflurane group having slightly better morphology, which is
      the most subjective of the parameters measured. The sevoflurane administrations
      were associated with slightly higher pulse rates and blood pressures. Sevoflurane
      provides a suitable alternative to propofol for anaesthesia in patients
      undergoing electroconvulsive therapy, although the slightly greater pulse rate
      rise and blood pressure rise should be considered in patients with ischaemic
      heart disease.

PMID- 15957723
TI  - Anaesthesia for electroconvulsive therapy: a comparison of sevoflurane with
      propofol.
AB  - This study was a prospective audit of patients receiving either intravenous
      induction of anaesthesia with propofol 2 mg/kg or inhalational induction using 8%
      sevoflurane for patients undergoing electroconvulsive therapy (ECT). All patients
      received inhaled 50% nitrous oxide. The anaesthetic agent was determined by
      psychiatrist preference. Each psychiatrist nominated only one induction technique
      for all his or her patients. Seventy treatments were studied in each group.
      Induction time was longer in the sevoflurane group. The time from commencing
      induction to loss of verbal contact was [mean (SD)] 64 (29.9) seconds for
      sevoflurane and 36 (33.6) seconds for propofol (P=0.001). Time to loss of eyelash
      reflex was 82 (32.6)s for sevoflurane and 44 (17.9)s for propofol (P<0.001). The
      duration of seizure activity was longer in sevoflurane patients, 35 (17.8)s,
      compared with 20 (9.8)s in the propofol group (P< 0.001). Discharge times were
      similar Minor adverse effects occurred in three patients, all in the sevoflurane
      group (one bradycardia and two episodes of post-procedural nausea). There were no
      major adverse events in either group. Propofol and sevoflurane both appear to be
      suitable agents for induction of anaesthesia for ECT.

PMID- 15957724
TI  - Oral ketamine or midazolam or low dose combination for premedication in children.
AB  - This randomized controlled trial was designed to evaluate whether the combination
      of low dose oral midazolam (0.25 mg/kg) and low dose oral ketamine (3 mg/kg)
      provides better premedication than oral midazolam (0.5 mg/kg) or oral ketamine (6
      mg/kg). Seventy-eight children of ASA physical status I or II scheduled for
      elective ophthalmic surgery were randomly divided into three groups and given
      premedication in the holding area 30 minutes before surgery. Two subjects from
      each group vomited the medication and were excluded, leaving 72 subjects for
      further analysis. The onset of sedation was earlier in the combination group than
      the other two groups. At 10 minutes after premedication 12.5% in the combination
      group had an acceptable sedation score compared with none in the other two
      groups. After 20 minutes 54% in the combination group had an acceptable sedation
      score, 21% in the midazolam group and 16% in the ketamine group (P<0.05). There
      were no significant differences in the parental separation score, response to
      induction and emergence score. The mean time for best parental separation score
      was significantly less in the combination group (19+/-8 min) than either the
      midazolam (28+/-7) or ketamine (29+/-7 min) groups (P<0.05). Recovery was earlier
      in the combination group, as the time required to reach a modified Aldrete score
      of 10 was significantly less in the combination group (22+/-5 min) than in the
      oral midazolam (36+/-11 min) or ketamine (38+/-8 min) groups. The incidence of
      excessive salivation was significantly higher in the ketamine alone group
      (P<0.05). In conclusion, the combination of oral ketamine (3 mg/kg) and midazolam
      (0.25 mg/kg) has minimal side effects and gives a faster onset and more rapid
      recovery than ketamine 6 mg/kg or midazolam 0.5 mg/kg for premedication in
      children.

PMID- 15957725
TI  - Comparison of propofol consumption and recovery time in Caucasians from Italy,
      with Chinese, Malays and Indians from Malaysia.
AB  - Differences in sensitivity to anaesthetic drugs may exist among different ethnic
      groups. Allelic variants for drug metabolizing isoenzymes and pharmacokinetic
      differences may account for a variable response to some anaesthetic drugs. This
      study was designed to compare propofol consumption and recovery characteristics
      in four ethnic groups: Chinese, Malays, and Indians in Malaysia and Caucasians in
      Italy. Patients undergoing total intravenous anaesthesia with propofol and
      fentanyl were evaluated for propofol consumption and recovery time. The
      Bispectral Index (BIS) was used to maintain the same anaesthesia depth in all
      patients. The BIS value, the response to verbal stimuli and eye-opening time were
      used to assess recovery. After propofol discontinuation the BIS values returned
      to baseline in 11+/-4.2 min for Caucasians, in 12.5+/-5.1 min for Chinese, 15.9+/
      6.3 min for Malays and 22.1+/-8.1 for Indians. Time to eye-opening was 11.63+/
      4.2 min in Caucasians, 13.23+/-4.9 min in Chinese, 16.97+/-5.2 min in Malays and
      22.3+/-6.6 min in Indians. The propofol consumption was significantly lower in
      Indians compared to the other three groups (P<0.01). The recovery of Indians was
      much slower compared to Chinese, Malays and Caucasians. The recovery time of
      Malays is significantly slower compared to Chinese and Caucasians. Differences in
      propofol consumption and recovery time were not significant between Chinese and
      Caucasians, but the ratio recovery time/propofol consumption was significantly
      lower in Caucasians compared to all the other groups.

PMID- 15957726
TI  - Muscle weakness after muscle relaxants: an audit of clinical practice.
AB  - Residual muscle weakness after general anaesthesia, assessed using handgrip
      strength, was audited in a teaching hospital. The relationships between residual
      weakness, the use of muscle relaxants and patient characteristics were examined.
      Handgrip strength was measured preoperatively, one hour postoperatively and one
      day postoperatively using a hand dynamometer in 151 patients having general
      anaesthesia. Forty-nine patients received no muscle relaxant, 34 patients
      received vecuronium and 68 received rocuronium. Patients were managed by their
      anaesthetist according to that anaesthetist's clinical choice. All patients who
      received muscle relaxants received neostigmine. One hour postoperatively, there
      was a decline in handgrip strength of 16% for the no relaxant group, 24% for
      vecuronium and 29% for rocuronium. The degree of weakness for the relaxant groups
      was unrelated to age (P=0.89) but was strongly influenced by the patient's sex.
      Almost all of the increased weakness with relaxants was found in the female
      patients. The mean decline in handgrip strength in the male patients who received
      either vecuronium or rocuronium was similar to that seen when relaxants had not
      been used (P=0.40). One hour postoperatively, female patients showed a marked
      decrease in handgrip strength after both vecuronium and rocuronium (32% and 34%
      respectively, combined P=0.01). These results suggest that in usual clinical
      practice at our institution, female patients are more likely to have residual
      weakness after muscle relaxants.

PMID- 15957727
TI  - Fatal systemic air embolism during endoscopic retrograde cholangio
      pancreatography.
AB  - Air embolism is a rare complication of gastrointestinal endoscopy. We present a
      56-year-old male who developed both venous and systemic arterial air embolism
      during an endoscopic retrograde cholangiopancreatogram. Despite early treatment
      based on clinical diagnosis and confirmation by transthoracic echocardiography,
      the patient died as a result of severe cerebral ischaemia. Risk factors
      associated with air embolism in gastrointestinal endoscopic procedures include
      situations where the mucosa is not intact or where high pressures are generated
      in the lumen of the gastrointestinal tract. Clinical diagnosis of air embolism
      during endoscopy is difficult and urgent echocardiography is the investigation of
      choice. Treatment is largely supportive but hyperbaric oxygen therapy should be
      considered in any severe cases, especially if neurological injury is present.

PMID- 15957728
TI  - An unexpectedly difficult intubation following repeated endoscopy.
AB  - A 67-year-old man required an urgent laparotomy for a bleeding gastric ulcer. He
      had undergone three upper gastrointestinal endoscopies over five days since
      admission to hospital. Tracheal intubation was unexpectedly difficult due to
      marked supraglottic oedema as well as unfavourable upper airway anatomy. A
      fibreoptic intubation through a laryngeal mask airway was performed with
      difficulty. The management of this case of difficult intubation following
      repeated endoscopy is presented.

PMID- 15957729
TI  - Airway problems related to laryngeal mask airway use associated with an
      undiagnosed epiglottic cyst.
AB  - This report describes airway management difficulties in a patient with an
      asymptomatic and undiagnosed epiglottic cyst. Mask ventilation after induction of
      general anesthesia was uneventful. Insertion of an LMA resulted in inadequate
      ventilation. Fiberoptic intubation through an intubating LMA was impossible
      because the LMA pushed the cyst into the laryngeal inlet. Fibreoptic intubation,
      assisted by the use of a direct laryngoscope without the LMA was uneventful.
      Preoperative craniocervical scans performed for assessment of other conditions
      may reveal asymptomatic pathology in the airway.

PMID- 15957730
TI  - Phrenic nerve palsy in severe tetanus.
AB  - Unilateral or bilateral raised hemidiaphragms were observed on chest X-ray in
      three patients with severe tetanus. Diaphragmatic movement was absent on
      ultrasonography and fluoroscopy. Nerve conduction study confirmed phrenic nerve
      palsy. Bilateral involvement caused delayed weaning from the ventilator, whereas
      unilateral involvement was asymptomatic. There was complete recovery from phrenic
      nerve palsy in all patients.

PMID- 15957731
TI  - Emergency anaesthesia in a patient with Gordon's syndrome.
AB  - Gordon's syndrome is a rare condition characterized by hypertension and
      hyperkalemia despite normal renal glomerular function. We report the
      administration of an anaesthetic to one such patient for an urgent surgical
      procedure. The patient's serum potassium was only marginally raised at the outset
      of the procedure. During surgery the serum potassium rose significantly, but
      responded to conventional management. Hyperkalaemia is a specific electrolyte
      disturbance that has numerous implications for the administration of an
      anaesthetic. Most importantly, there is a danger that further acute elevations
      may occur, caused by the surgery, the anaesthetic, or the condition itself

PMID- 15957732
TI  - Custom built bite-block endotracheal tube holder for prolonged intubation.
AB  - This case report describes an intensive care patient with recurrent endotracheal
      tube occlusion due to biting. The use and fabrication of a new form of custom
      built bite-block to resolve these problems is described. The device described may
      also provide better access for mouth care and simplify airway management compared
      with bite-blocks commonly used.

PMID- 15957733
TI  - Knotted femoral nerve catheter.
AB  - We describe a case of knotting of a femoral nerve catheter which prevented
      removal by traction after knee replacement surgery. In this context, early
      surgical removal should be performed as bacterial colonization of femoral
      catheters is common. Radiological imaging of the catheter may assist decision
      making about whether to persist with traction and what surgical approach is
      required. Minimizing the length of catheter inserted to less than 10 cm makes
      knotting unlikely, but will decrease the chance of achieving lumbar plexus
      blockade which could improve analgesia if the catheter passes centrally.

PMID- 15957734
TI  - Activated protein C for the treatment of fulminant meningococcal septicaemia.
AB  - We report two cases of meningococcal septic shock with multiple organ failure
      treated with prompt administration of activated protein C. This was associated
      with a rapid clinical improvement and early cessation of organ support. Both
      patients survived to hospital discharge with no long-term sequelae.

PMID- 15957735
TI  - Postoperative pain management after intravenous remifentanil.

PMID- 15957736
TI  - Are anaesthetists prone to suicide? A review of rates and risk factors.

PMID- 15957737
TI  - Unusual effect of suxamethonium.

PMID- 15957738
TI  - A unified view of imaging the elastic properties of tissue.
AB  - A number of different approaches have been developed to estimate and image the
      elastic properties of tissue. The biomechanical properties of tissues are vitally
      linked to function and pathology, but cannot be directly assessed by conventional
      ultrasound, MRI, CT, or nuclear imaging. Research developments have introduced
      new approaches, using either MRI or ultrasound to image the tissue response to
      some stimulus. A wide range of stimuli has been evaluated, including heat, water
      jets, vibration shear waves, compression, and quasistatic compression, using
      single or multiple steps or low-frequency (<10 Hz) cyclic excitation. These may
      seem to be greatly dissimilar, and appear to produce distinctly different types
      of information and images. However, our purpose in this tutorial is to review the
      major classes of excitation stimuli, and then to demonstrate that they produce
      responses that fall within a common spectrum of elastic behavior. Within this
      spectrum, the major classes of excitation include step compression, cyclic
      quasistatic compression, harmonic shear wave excitation, and transient shear wave
      excitation. The information they reveal about the unknown elastic distribution
      within an imaging region of interest are shown to be fundamentally related
      because the tissue responses are governed by the same equation. Examples use
      simple geometry to emphasize the common nature of the approaches.

PMID- 15957739
TI  - Ultrasonic relaxation and internal rotation in butyl formate.

PMID- 15957740
TI  - Transmission loss measurement of consolidated granular media.

PMID- 15957741
TI  - Sound of shallow and deep water lobsters: measurements, analysis, and
      characterization.

PMID- 15957742
TI  - Atypical calling by a blue whale in the Gulf Of Alaska.

PMID- 15957743
TI  - Evoked-potential audiogram of the Yangtze finless porpoise Neophocaena
      phocaenoides asiaeorientalis.

PMID- 15957744
TI  - Wave-induced fluid flow in random porous media: attenuation and dispersion of
      elastic waves.
AB  - A detailed analysis of the relationship between elastic waves in inhomogeneous,
      porous media and the effect of wave-induced fluid flow is presented. Based on the
      results of the poroelastic first-order statistical smoothing approximation
      applied to Biot's equations of poroelasticity, a model for elastic wave
      attenuation and dispersion due to wave-induced fluid flow in 3-D randomly
      inhomogeneous poroelastic media is developed. Attenuation and dispersion depend
      on linear combinations of the spatial correlations of the fluctuating poroelastic
      parameters. The observed frequency dependence is typical for a relaxation
      phenomenon. Further, the analytic properties of attenuation and dispersion are
      analyzed. It is shown that the low-frequency asymptote of the attenuation
      coefficient of a plane compressional wave is proportional to the square of
      frequency. At high frequencies the attenuation coefficient becomes proportional
      to the square root of frequency. A comparison with the 1-D theory shows that
      attenuation is of the same order but slightly larger in 3-D random media. Several
      modeling choices of the approach including the effect of cross correlations
      between fluid and solid phase properties are demonstrated. The potential
      application of the results to real porous materials is discussed.

PMID- 15957745
TI  - Energy transmission in a mechanically-linked double-wall structure coupled to an
      acoustic enclosure.
AB  - The energy transmission in a mechanically linked double-wall structure into an
      acoustic enclosure is studied in this paper. Based on a fully coupled vibro
      acoustic formulation, focus is put on investigating the effect of the air gap and
      mechanical links between the two panels on the energy transmission and noise
      insulation properties of such structures. An approximate formula reflecting the
      gap effect on the lower-order coupled frequencies of the system is proposed. A
      criterion, based on the ratio between the aerostatic stiffness of the gap cavity
      and the stiffness of the link, is proposed to predict the dominant transmitting
      path, with a view to provide guidelines for the design of appropriate control
      strategies. Numerical results reveal the existence of three distinct zones,
      within which energy transmission takes place following different mechanisms and
      transmitting paths. Corresponding effects on noise insulation properties of the
      double-wall structure are also investigated.

PMID- 15957746
TI  - Contactless micromanipulation of small particles by an ultrasound field excited
      by a vibrating body.
AB  - A method is presented to position and displace micron-sized particles of a
      diameter between 10 and 100 microm without contact to solid instruments. An
      ultrasound field is utilized for this purpose. It is excited in a fluid-filled
      gap between a harmonically vibrating body and a rigid plane surface of an
      arbitrary other body, e.g., an object slide or a wafer. In this ultrasound field
      a force field is established, which acts on the particles suspended in the fluid
      and moves them to certain positions. The advantage of the method is that it is
      possible to manipulate single particles or many particles in parallel on any
      surface, for example, on a structured wafer. Theoretical calculations of the
      force field and experimental results including three principles to displace
      particles with micrometer accuracy are shown. The method might be used for
      microassembly or cell manipulation and treatment.

PMID- 15957747
TI  - Influence of viscosity on the diffraction of sound by a periodic array of
      screens.
AB  - The paper contains an analysis of the transmission of a pressure wave through a
      periodic grating including the influence of the air viscosity. The system of
      equations in this case consists of the compressible Navier-Stokes equations
      associated with no-slip boundary conditions on solid surfaces. The problem is
      reduced to two hypersingular integral equations for determining the velocity
      components along the slits. These equations are solved by using Galerkin's method
      with some special trial functions. The results can be applied in designing
      protective screens for miniature microphones realized in the technology of micro
      electro-mechanical systems (MEMS). In this case, the physical dimensions of the
      device are on the order of the viscous boundary layer so that the viscosity
      cannot be neglected. The microfluidic model of the screen consists of a periodic
      array of slits in a substrate. The analysis indicates that the openings in the
      screen should be on the order of 10 microm in order to avoid excessive
      attenuation of the signal.

PMID- 15957748
TI  - Acoustic positioning using multiple microphone arrays.
AB  - Passive acoustic techniques are presented to solve the localization problem of a
      sound source in three-dimensional space using off-the-shelf hardware. Multiple
      microphone arrays are employed, which operate independently, in estimating the
      direction of arrival of sound, or, equivalently, a direction vector from the
      array's geometric center towards the source. Direction vectors and array centers
      are communicated to a central processor, where the source is localized by finding
      the intersection of the direction lines defined by the direction vectors and the
      associated array centers. The performance of the method in the air is
      demonstrated experimentally and compared with a state-of-the-art method that
      requires centralized digitization of the signals from the microphones of all the
      arrays.

PMID- 15957749
TI  - Shallow water sound propagation with surface waves.
AB  - The theory of wavefront modeling in underwater acoustics is extended to allow
      rapid range dependence of the boundaries such as occurs in shallow water with
      surface waves. The theory allows for multiple reflections at surface and bottom
      as well as focusing and defocusing due to reflection from surface waves. The
      phase and amplitude of the field are calculated directly and used to model pulse
      propagation in the time domain. Pulse waveforms are obtained directly for all
      wavefront arrivals including both insonified and shadow regions near caustics.
      Calculated waveforms agree well with a reference solution and data obtained in a
      near-shore shallow water experiment with surface waves over a sloping bottom.

PMID- 15957750
TI  - Simulations of optoacoustic wave propagation in light-absorbing media using a
      finite-difference time-domain method.
AB  - Optoacoustic (OA) imaging is an emerging technology that combines the high
      optical contrast of tissues with the high spatial resolution of ultrasound.
      Taking full advantage of OA imaging requires a better understanding of OA wave
      propagation in light-absorbing media. Current simulation methods are mainly based
      on simplified conditions such as thermal confinement, negligible viscosity, and
      homogeneous acoustic properties throughout the image object. In this study a new
      numerical approach is proposed based on a finite-difference time-domain (FDTD)
      method to solve the general OA equations, comprising the continuity, Navier
      Stokes, and heat-conduction equations. The FDTD code was validated using a
      benchmark problem that has an approximate analytical solution. OA experiments
      were also conducted and data were in good agreement with those predicted by the
      FDTD method. Characteristics of simulated OA waveforms and OA images were
      discussed. The simulator was also employed to study wavefront distortion in OA
      breast imaging.

PMID- 15957751
TI  - Optimal design of loudspeaker arrays for robust cross-talk cancellation using the
      Taguchi method and the genetic algorithm.
AB  - An optimal design technique of loudspeaker arrays for cross-talk cancellation
      with application in three-dimensional audio is presented. An array focusing
      scheme is presented on the basis of the inverse propagation that relates the
      transducers to a set of chosen control points. Tikhonov regularization is
      employed in designing the inverse cancellation filters. An extensive analysis is
      conducted to explore the cancellation performance and robustness issues. To best
      compromise the performance and robustness of the cross-talk cancellation system,
      optimal configurations are obtained with the aid of the Taguchi method and the
      genetic algorithm (GA). The proposed systems are further justified by physical as
      well as subjective experiments. The results reveal that large number of
      loudspeakers, closely spaced configuration, and optimal control point design all
      contribute to the robustness of cross-talk cancellation systems (CCS) against
      head misalignment.

PMID- 15957752
TI  - Locally periodic Timoshenko rod: experiment and theory.
AB  - The flexural vibrations of a locally periodic rod, which consists of N unit
      cells, are discussed both from the experimental and theoretical points of view.
      Timoshenko's beam theory and the transfer matrix method are used to calculate the
      normal-mode frequencies and amplitudes. The theoretical values are then compared
      with the experimental ones, which are obtained using an electromagnetic acoustic
      transducer (EMAT). Good agreement between the numerical results and the
      experimental measurements is obtained. It is shown that as N grows, a band
      spectrum emerges.

PMID- 15957753
TI  - Comparison of structural response and fatigue endurance of aircraft flap-like box
      structures subjected to acoustic loading.
AB  - The results of an extensive test program to characterize the behavior of typical
      aircraft structures under acoustic loading and to establish their fatigue
      endurance are presented. The structures tested were the three flap-like box-type
      of structures. Each structure consisted of one flat (bottom) and one curved (top)
      stiffener stiffened skin panel, front, and rear spars, and ribs that divided the
      structures into three bays. The three structures, constructed from three
      different materials (aircraft standard aluminum alloy, Carbon Fibre Reinforced
      Plastic, and a Glass Fibre Metal Laminate, i.e., GLARE) had the same size and
      configuration, with only minor differences due to the use of different materials.
      A first set of acoustic tests with excitations of intensity ranging from 140 to
      160 dB were carried out to obtain detailed data on the dynamic response of the
      three structures. The FE analysis of the structures is also briefly described and
      the results compared with the experimental data. The fatigue endurance of the
      structures was then determined using random acoustic excitation with an overall
      sound pressure level of 161 dB, and details of crack propagation are reported.

PMID- 15957754
TI  - Finite element prediction of wave motion in structural waveguides.
AB  - A method is presented by which the wavenumbers for a one-dimensional waveguide
      can be predicted from a finite element (FE) model. The method involves
      postprocessing a conventional, but low order, FE model, the mass and stiffness
      matrices of which are typically found using a conventional FE package. This is in
      contrast to the most popular previous waveguide/FE approach, sometimes termed the
      spectral finite element approach, which requires new spectral element matrices to
      be developed. In the approach described here, a section of the waveguide is
      modeled using conventional FE software and the dynamic stiffness matrix formed. A
      periodicity condition is applied, the wavenumbers following from the
      eigensolution of the resulting transfer matrix. The method is described,
      estimation of wavenumbers, energy, and group velocity discussed, and numerical
      examples presented. These concern wave propagation in a beam and a simply
      supported plate strip, for which analytical solutions exist, and the more complex
      case of a viscoelastic laminate, which involves postprocessing an ANSYS FE model.
      The method is seen to yield accurate results for the wavenumbers and group
      velocities of both propagating and evanescent waves.

PMID- 15957755
TI  - A categorization method applied to the study of urban road traffic noise.
AB  - The present work summarizes a study of the hypothesis that urban noise can be
      stratified by measuring street noise according to a prior classification of a
      town's streets according to their use in communicating the different zones of the
      town. The method was applied to five medium-sized Spanish towns (Vitoria-Gasteiz,
      Salamanca, Badajoz, Caceres, and Merida) with populations ranging from 218 000
      down to 50000 and with different socio-economic characteristics, climate, etc. As
      the initial hypothesis of the work was that traffic is the main source of urban
      noise and is also the principal cause of the variability of the sound levels
      measured in urban settings, the study focused only on the five nonpedestrian
      categories of streets. The continuous equivalent sound level (Leq) was employed
      in the statistical analysis as it is commonly used as a general noise index, and
      other noise indicators such as L(DN) or L(DEN) are calculated from it. It was
      found that, although differences between the medians were not statistically
      significant in some of the towns for certain pairs of adjacent categories, the
      differences between pairs of nonadjacent categories were always significant,
      indicative of the stratification of noise in these five towns. Further studies on
      other medium-sized towns and on large towns and small villages would be needed to
      test whether the present definition of street categories is extensible elsewhere
      without modification.

PMID- 15957756
TI  - Effect of season and meteorological conditions on community noise annoyance.
AB  - More than 80 000 residents' responses to transportation noise from 42 studies
      conducted at different times of year provide statistical estimates of the effects
      of season and meteorological conditions on community response to noise. The
      strongest evidence for a seasonal effect comes from 7 years of continuous daily
      interviewing of nationally representative probability samples in the Netherlands.
      Long-term annoyance with noise is slightly, but statistically significantly,
      higher in the summer than in the winter. Analyses of 41 other surveys drawn from
      diverse countries, climates, and times of year also provide evidence that noise
      annoyance varies over the year, is increased by temperature, and may be increased
      by more sunshine, less precipitation, and reduced wind speeds. These findings are
      not sufficiently precise to determine whether the apparent relationships with
      meteorological conditions are only the result of seasonal variations or are also
      the result of differences in the climate at different locations. There is not
      consistent evidence that the meteorological conditions on the day of the
      interview or the immediately preceding days have any more effect on long-term
      noise annoyance measures than do the conditions over the immediately preceding
      weeks or months.

PMID- 15957757
TI  - Time reversal of noise sources in a reverberation room.
AB  - Usually, time reversal is studied with pulsed emissions. Here, the properties of
      time reversal of the acoustic field emitted by noise sources in a reverberation
      room are studied numerically, theoretically, and experimentally. A time domain
      numerical simulation of a two-dimensional enclosure shows that the intensity of a
      time-reversed noise is strongly enhanced right on the initial source position. A
      theory based on the link that exists between time reversal of noise and the "well
      known" time reversal of short pulse is developed. One infers that the focal spot
      size equals half a wavelength and the signal to noise ratio only depends on the
      number of transceivers in the time reversal mirror. This last property is
      characteristic of the time reversal of noise. Experimental results are obtained
      in a 5 X 3 X 3 m3 reverberation room. The working frequency range varies from 300
      Hz to 2 kHz. The ability of the time reversal process to physically reconstruct
      the image of two noise sources is studied. To this end, care is given to the
      technique to separate two close random sources, and also to the influence of
      temperature fluctuations on the focusing quality.

PMID- 15957758
TI  - Acoustic analysis in Mudejar-Gothic churches: experimental results.
AB  - This paper describes the preliminary results of research work in acoustics,
      conducted in a set of 12 Mudejar-Gothic churches in the city of Seville in the
      south of Spain. Despite common architectural style, the churches feature
      individual characteristics and have volumes ranging from 3947 to 10 708 m3.
      Acoustic parameters were measured in unoccupied churches according to the ISO
      3382 standard. An extensive experimental study was carried out using impulse
      response analysis through a maximum length sequence measurement system in each
      church. It covered aspects such as reverberation (reverberation times, early
      decay times), distribution of sound levels (sound strength); early to late sound
      energy parameters derived from the impulse responses (center time, clarity for
      speech, clarity, definition, lateral energy fraction), and speech intelligibility
      (rapid speech transmission index), which all take both spectral and spatial
      distribution into account. Background noise was also measured to obtain the NR
      indices. The study describes the acoustic field inside each temple and
      establishes a discussion for each one of the acoustic descriptors mentioned by
      using the theoretical models available and the principles of architectural
      acoustics. Analysis of the quality of the spaces for music and speech is carried
      out according to the most widespread criteria for auditoria.

PMID- 15957759
TI  - Acoustic impedance measurements-correction for probe geometry mismatch.
AB  - The effect of evanescent mode generation, due to geometrical mismatch, in
      acoustic impedance measurements is investigated. The particular geometry
      considered is that of a impedance probe with an annular flow port and a central
      microphone, but the techniques are applicable to other geometries. It is found
      that the imaginary part of the measured impedance error is proportional to
      frequency, and that the sign of the error is positive for measurements made on
      tubes with diameter much larger than that of the inlet port, but negative for
      tubes with diameter close to that of the inlet. The result is a distortion of the
      measured frequencies of the impedance minima of the duct while the maxima are
      largely unaffected. There is, in addition, a real resistive component to the
      error that varies approximately as the square root of the frequency. Experiment
      confirms the results of the analysis and calculations, and a calibration
      procedure is proposed that allows impedance probes that have been calibrated on a
      semi-infinite tube of one diameter to be employed for measurements on components
      with an inlet duct of some very different diameter.

PMID- 15957760
TI  - Instantaneous frequency decomposition: an application to spectrally sparse sounds
      with fast frequency modulations.
AB  - Classical time-frequency analysis is based on the amplitude responses of bandpass
      filters, discarding phase information. Instantaneous frequency analysis, in
      contrast, is based on the derivatives of these phases. This method of frequency
      calculation is of interest for its high precision and for reasons of similarity
      to cochlear encoding of sound. This article describes a methodology for high
      resolution analysis of sparse sounds, based on instantaneous frequencies. In this
      method, a comparison between tonotopic and instantaneous frequency information is
      introduced to select filter positions that are well matched to the signal.
      Second, a cross-check that compares frequency estimates from neighboring channels
      is used to optimize filter bandwidth, and to signal the quality of the analysis.
      These cross-checks lead to an optimal time-frequency representation without
      requiring any prior information about the signal. When applied to a signal that
      is sufficiently sparse, the method decomposes the signal into separate time
      frequency contours that are tracked with high precision. Alternatively, if the
      signal is spectrally too dense, neighboring channels generate inconsistent
      estimates-a feature that allows the method to assess its own validity in
      particular contexts. Similar optimization principles may be present in cochlear
      encoding.

PMID- 15957761
TI  - Adaptive window-length detection of underwater transients using wavelets.
AB  - This paper describes a detection method that adapts to unknown characteristics of
      the underlying transient signal, such as location, length, and time-frequency
      content. It applies a set of embedded detectors tuned to a number of signal
      partitions. The detectors are based on the wavelet theory, whereby two different
      techniques are examined, one using local Fourier transform and the other using
      discrete wavelet transform. The detection statistics are computed so as to enable
      prewhitening of unknown colored noise and to allow for a constant false-alarm
      rate detection. An adapted segmentation of the signal is next obtained with a
      goal of finding the largest detection statistics within each segment of the
      partition. The detectors are tested using several underwater acoustic transient
      signals buried in ambient sea noise.

PMID- 15957762
TI  - Application of acoustic reflection tomography to sonar imaging.
AB  - Computer-aided tomography is a technique for providing a two-dimensional cross
      sectional view of a three-dimensional object through the digital processing of
      many one-dimensional views (or projections) taken at different look directions.
      In acoustic reflection tomography, insonifying the object and then recording the
      backscattered signal provides the projection information for a given look
      direction (or aspect angle). Processing the projection information for all
      possible aspect angles enables an image to be reconstructed that represents the
      two-dimensional spatial distribution of the object's acoustic reflectivity
      function when projected on the imaging plane. The shape of an idealized object,
      which is an elliptical cylinder, is reconstructed by applying standard
      backprojection, Radon transform inversion (using both convolution and filtered
      backprojections), and direct Fourier inversion to simulated projection data. The
      relative merits of the various reconstruction algorithms are assessed and the
      resulting shape estimates compared. For bandpass sonar data, however, the wave
      number components of the acoustic reflectivity function that are outside the
      passband are absent. This leads to the consideration of image reconstruction for
      bandpass data. Tomographic image reconstruction is applied to real data collected
      with an ultra-wideband sonar transducer to form high-resolution acoustic images
      of various underwater objects when the sonar and object are widely separated.

PMID- 15957763
TI  - Hilbert space inverse wave imaging in a planar multilayer environment.
AB  - Most diffraction tomography (DT) algorithms use a homogeneous Green function (GF)
      regardless of the medium being imaged. This choice is usually motivated by
      practical considerations: analytic inversions in standard geometries (Cartesian,
      spherical, etc.) are significantly simplified by the use of a homogeneous GF,
      estimating a nonhomogeneous GF can be very difficult, as can incorporating a
      nonhomogeneous GF into standard DT algorithms. Devaney has circumvented these
      issues by developing a purely numerical DT inversion algorithm [A. J. Devaney and
      M. Dennison, Inverse Probl. 19, 855-870 (2003)] that is independent of
      measurement system geometry, number of frequencies used in the reconstruction,
      and GF. A planar multilayer GF has been developed for use in Devaney's "Hilbert
      space" algorithm and used in a proof-of-principle nondestructive evaluation (NDE)
      experiment to image noninvasively a flaw in an aluminum/copper planar multilayer
      medium using data collected from an ultrasonic measurement system. The data were
      collected in a multistatic method with no beamforming: all focusing through the
      multilayer was performed mathematically "after-the-fact," that is, after the data
      were collected.

PMID- 15957764
TI  - Optimal nonlocal boundary control of the wide-angle parabolic equation for
      inversion of a waveguide acoustic field.
AB  - This paper applies the concept of optimal boundary control for solving inverse
      problems in shallow water acoustics. To treat the controllability problem, a
      continuous analytic adjoint model is derived for the Claerbout wide-angle
      parabolic equation (PE) using a generalized nonlocal impedance boundary condition
      at the water-bottom interface. While the potential of adjoint methodology has
      been recently demonstrated for ocean acoustic tomography, this approach combines
      the advantages of exact transparent boundary conditions for the wide-angle PE
      with the concept of adjoint-based optimal control. In contrast to meta-heuristic
      approaches the inversion procedure itself is directly controlled by the waveguide
      physics and, in a numerical implementation based on conjugate gradient
      optimization, many fewer iterations are required for assessment of an environment
      that is supported by the underlying subbottom model. Furthermore, since
      regularization schemes are particularly important to enhance the performance of
      full-field acoustic inversion, special attention is devoted to the application of
      penalization methods to the adjoint optimization formalism. Regularization
      incorporates additional information about the desired solution in order to
      stabilize ill-posed inverse problems and identify useful solutions, a feature
      that is of particular importance for inversion of field data sampled on a
      vertical receiver array in the presence of measurement noise and modeling
      uncertainty. Results with test data show that the acoustic field and the bottom
      properties embedded in the control parameters can be efficiently retrieved.

PMID- 15957765
TI  - Dispersion-based short-time Fourier transform applied to dispersive wave
      analysis.
AB  - Although time-frequency analysis is effective for characterizing dispersive wave
      signals, the time-frequency tilings of most conventional analysis methods do not
      take into account dispersion phenomena. An adaptive time-frequency analysis
      method is introduced whose time-frequency tiling is determined with respect to
      the wave dispersion characteristics. In the dispersion-based time-frequency
      tiling, each time-frequency atom is adaptively rotated in the time-frequency
      plane, depending on the local wave dispersion. Although this idea can be useful
      in various problems, its application to the analysis of dispersive wave signals
      has not been made. In this work, the adaptive time-frequency method was applied
      to the analysis of dispersive elastic waves measured in waveguide experiments and
      a theoretical investigation on its time-frequency resolution was presented. The
      time-frequency resolution of the proposed transform was then compared with that
      of the standard short-time Fourier transform to show its effectiveness in dealing
      with dispersive wave signals. In addition, to facilitate the adaptive time
      frequency analysis of experimentally measured signals whose dispersion relations
      are not known, an iterative scheme for determining the relationships was
      developed. The validity of the present approach in dealing with dispersive waves
      was verified experimentally.

PMID- 15957766
TI  - Exploring interaction effects in two-component gas mixtures using orthogonal
      signal correction of ultrasound pulses.
AB  - Within Sweden and the EU, an increased use of biogas gas and natural gas is
      encouraged to decrease emission of carbon dioxide. To support more effective
      manufacturing, distribution, and consumption of energy gases, new methods for the
      measurement of the calorimetric value or the gas composition are needed. This
      paper presents a method to extract and visualize variations in ultrasound pulse
      shape, caused by interaction effects between the constituents of a two-component
      gas mixture. The method is based on a combination of principal component analysis
      and orthogonal signal correction. Pulse-echo ultrasound experiments on mixtures
      of oxygen and ethane in the concentration range from 20% to 80% ethane show that
      the extracted information could be correlated with the molar fraction of ethane
      in the mixture.

PMID- 15957767
TI  - Distortion product otoacoustic emissions for hearing threshold estimation and
      differentiation between middle-ear and cochlear disorders in neonates.
AB  - Our aim in the present study was to apply extrapolated DPOAE I/O-functions [J.
      Acoust. Soc. Am. 111, 1810-1818 (2002); 113, 3275-3284 (2003)] in neonates in
      order to investigate their ability to estimate hearing thresholds and to
      differentiate between middle-ear and cochlear disorders. DPOAEs were measured in
      neonates after birth (mean age = 3.2 days) and 4 weeks later (follow-up) at 11
      test frequencies between f2 = 1.5 and 8 kHz and compared to that found in normal
      hearing subjects and cochlear hearing loss patients. On average, in a single ear
      hearing threshold estimation was possible at about 2/3 of the test frequencies. A
      sufficient test performance of the approach is therefore suggested. Thresholds
      were higher at the first measurement compared to that found at the follow-up
      measurement. Since thresholds varied with frequency, transitory middle ear
      dysfunction due to amniotic fluid instead of cochlear immaturity is suggested to
      be the cause for the change in thresholds. DPOAE behavior in the neonate ears
      differed from that found in the cochlear hearing loss ears. From a simple model
      it was concluded that the difference between the estimated DPOAE threshold and
      the DPOAE detection threshold is able to differentiate between sound conductive
      and cochlear hearing loss.

PMID- 15957768
TI  - Level dependence of distortion-product otoacoustic emissions measured at high
      frequencies in humans.
AB  - Given that high-frequency hearing is most vulnerable to cochlear pathology, it is
      important to characterize distortion-product otoacoustic emissions (DPOAEs)
      measured with higher-frequency stimuli in order to utilize these measures in
      clinical applications. The purpose of this study was to explore the dependence of
      DPOAE amplitude on the levels of the evoking stimuli at frequencies greater than
      8 kHz, and make comparisons with those data that have been extensively measured
      with lower-frequency stimuli. To accomplish this, DPOAE amplitudes were measured
      at six different f2 frequencies (2, 5, 10, 12, 14, and 16 kHz), with a frequency
      ratio (f2/f1) of 1.2, at five fixed levels (30 to 70 dB SPL) of one primary
      (either f1 or f2), while the other primary was varied in level (30 to 70 dB SPL).
      Generally, the level separation between the two primary tones (L1 > L2)
      generating the largest DPOAE amplitude (referred to as the "optimal level
      separation") decreased as the level of the fixed primary increased. Additionally,
      the optimal level separation was frequency dependent, especially at the lower
      fixed primary tone levels ( < or = 50 dB SPL). In agreement with previous
      studies, the DPOAE level exhibited greater dependence on L1 than on L2.

PMID- 15957769
TI  - Using the short-time correlation coefficient to compare transient- and derived,
      noise-evoked otoacoustic emission temporal waveforms.
AB  - Transient-evoked otoacoustic emissions (TEOAEs) and derived, noise-evoked
      otoacoustic emissions (derived-NEOAEs) were measured in seven normally hearing
      subjects. The evoked OAEs were all recorded at three excitation levels chosen to
      ensure that the OAE level curve compressive region was reached. The short-time
      correlation coefficient (STCC) was used to compare the OAE waveforms at different
      excitation levels, and thus estimate the time over which the response exceeds the
      noise level. The short-time correlation for TEOAEs is significant for longer than
      it is for NEOAEs, particularly in some individuals, and the STCC allows this to
      be quantified. This suggests that derived NEOAEs do not display the highly
      synchronized dominant frequencies often seen in TEOAEs. This has been confirmed
      by examining the derived frequency responses for the two types of excitation.
      Conventional TEOAEs thus appear to measure a combination of two conceptually
      different processes, while NEOAEs measure just one.

PMID- 15957770
TI  - Two-tone distortion in intracochlear pressure.
AB  - Two-tone distortion was measured in the intracochlear pressure in the base of the
      gerbil cochlea, close to the sensory tissue, where the local motions and forces
      of the organ of Corti can be detected. The measurements probe both the underlying
      nonlinear process that generates two-tone distortion, and the filtering and
      spreading of the distortion products. Some of our findings are as follows: (1)
      The observations were consistent with previous observations of two-tone
      distortion in BM motion [J. Neurophysiol. 77, 2385-2399 (1997); J. Neurophysiol.
      78, 261-270 (1997)]. (2) Frequency sweeps show distortion product tuning and
      phase-versus-frequency behavior that is similar, but not identical, to single
      tone tuning. (3) The decay of distortion products with distance from the basilar
      membrane confirms the feasibility that they could drive the stapes by a direct
      fluid route, as proposed by Ren [Nat. Neurosci. 7, 333-334 (2004)]. (4) The
      phases of the distortion products within a single family (the group of distortion
      products generated by a single primary pair) in some cases alternated between 0
      degrees and 180 degrees when referenced to the phases of the primaries. This
      behavior is predicted by a simple compressive nonlinearity.

PMID- 15957771
TI  - The effects of neural synchronization and peripheral compression on the acoustic
      reflex threshold.
AB  - This study investigates the acoustic reflex threshold (ART) dependency on
      stimulus phase utilizing low-level reflex audiometry [Neumann et al., Audiol.
      Neuro-Otol. 1, 359-369 (1996)]. The goal is to obtain optimal broadband stimuli
      for elicitation of the acoustic reflex and to obtain objective determinations of
      cochlear hearing loss. Three types of tone complexes with different phase
      characteristics were investigated: A stimulus that compensates for basilar
      membrane dispersion, thus causing a large overall neural synchrony (basilar
      membrane tone complex-BMTC), the temporally inversed stimulus (iBMTC), and random
      phase tone complexes (rTC). The ARTs were measured in eight normal-hearing and
      six hearing-impaired subjects. Five different conditions of peak amplitude and
      stimulus repetition rate were used for each stimulus type. The results of the
      present study suggest that the ART is influenced by at least two different
      factors: (a) the degree of synchrony of neural activity across frequency, and (b)
      the fast-acting compression mechanism in the cochlea that is reduced in the case
      of a sensorineural hearing loss. The results allow a clear distinction of the two
      subjects groups based on the different ART for the utilized types and conditions
      of the stimuli. These differences might be useful for objective recruitment
      detection in clinical diagnostics.

PMID- 15957773
TI  - Detection, direction discrimination, and off-frequency interference of center
      frequency modulations and glides for vowel formants.
AB  - Vowels are mainly classified by the positions of peaks in their frequency
      spectra, the formants. For normal-hearing subjects, change detection and
      direction discrimination were measured for linear glides in the center frequency
      (CF) of formantlike sounds. A CF rove was used to prevent subjects from using
      either the start or end points of the glides as cues. In addition, change
      detection and starting-phase (start-direction) discrimination were measured for
      similar stimuli with a sinusoidal 5-Hz formant-frequency modulation. The stimuli
      consisted of single formants generated using a number of different stimulus
      parameters including fundamental frequency, spectral slope, frequency region, and
      position of the formant relative to the harmonic spectrum. The change detection
      thresholds were in good agreement with the predictions of a model which analyzed
      and combined the effects of place-of-excitation and temporal cues. For most
      stimuli, thresholds were approximately equal for change detection and start
      direction discrimination. Exceptions were found for stimuli that consisted of
      only one or two harmonics. In a separate experiment, it was shown that change
      detection and start-direction discrimination of linear and sinusoidal formant
      frequency modulations were impaired by off-frequency frequency-modulated
      interferers. This frequency modulation detection interference was larger for
      formants with shallow than for those with steep spectral slopes.

PMID- 15957772
TI  - Comparing different estimates of cochlear compression in listeners with normal
      and impaired hearing.
AB  - A loss of cochlear compression may underlie many of the difficulties experienced
      by hearing-impaired listeners. Two behavioral forward-masking paradigms that have
      been used to estimate the magnitude of cochlear compression are growth of masking
      (GOM) and temporal masking (TM). The aim of this study was to determine whether
      these two measures produce within-subjects results that are consistent across a
      range of signal frequencies and, if so, to compare them in terms of reliability
      or efficiency. GOM and TM functions were measured in a group of five normal
      hearing and five hearing-impaired listeners at signal frequencies of 1000, 2000,
      and 4000 Hz. Compression values were derived from the masking data and confidence
      intervals were constructed around these estimates. Both measures produced
      comparable estimates of compression, but both measures have distinct advantages
      and disadvantages, so that the more appropriate measure depends on factors such
      as the frequency region of interest and the degree of hearing loss. Because of
      the long testing times needed, neither measure is suitable for clinical use in
      its current form.

PMID- 15957775
TI  - The spatial unmasking of speech: evidence for within-channel processing of
      interaural time delay.
AB  - Across-frequency processing by common interaural time delay (ITD) in spatial
      unmasking was investigated by measuring speech reception thresholds (SRTs) for
      high- and low-frequency bands of target speech presented against concurrent
      speech or a noise masker. Experiment 1 indicated that presenting one of these
      target bands with an ITD of +500 micros and the other with zero ITD (like the
      masker) provided some release from masking, but full binaural advantage was only
      measured when both target bands were given an ITD of + 500 micros. Experiment 2
      showed that full binaural advantage could also be achieved when the high- and low
      frequency bands were presented with ITDs of equal but opposite magnitude (+/- 500
      micros). In experiment 3, the masker was also split into high- and low-frequency
      bands with ITDs of equal but opposite magnitude (+/-500 micros). The ITD of the
      low-frequency target band matched that of the high-frequency masking band and
      vice versa. SRTs indicated that, as long as the target and masker differed in ITD
      within each frequency band, full binaural advantage could be achieved. These
      results suggest that the mechanism underlying spatial unmasking exploits
      differences in ITD independently within each frequency channel.

PMID- 15957774
TI  - Pitch strength of regular-interval click trains with different length "runs" of
      regular intervals.
AB  - Click trains were generated with first- and second-order statistics following
      Kaernbach and Demany [J. Acoust. Soc. Am. 104, 2298-2306 (1998)]. First-order
      intervals are between successive clicks, while second-order intervals are those
      between every other click. Click trains were generated with a repeating
      alternation of fixed and random intervals which produce a pitch at the reciprocal
      of the duration of the fixed interval. The intervals were then randomly shuffled
      and compared to the unshuffled, alternating click trains in pitch-strength
      comparison experiments. In almost all comparisons for the first-order interval
      stimuli, the shuffled-interval click trains had a stronger pitch strength than
      the unshuffled-interval click trains. The shuffled-interval click trains only
      produced stronger pitches for second-order interval stimuli when the click trains
      were unfiltered. Several experimental conditions and an analysis of runs of
      regular and random intervals in these click trains suggest that the auditory
      system is sensitive to runs of regular intervals in a stimulus that contains a
      mix of regular and random intervals. These results indicate that fine-structure
      regularity plays a more important role in pitch perception than randomness, and
      that the long-term autocorrelation function or spectra of these click trains are
      not good predictors of pitch strength.

PMID- 15957776
TI  - Observer weighting strategies in interaural time-difference discrimination and
      monaural level discrimination for a multi-tone complex.
AB  - Two experiments measured listeners' abilities to weight information from
      different components in a complex of 553, 753, and 953 Hz. The goal was to
      determine whether or not the ability to adjust perceptual weights generalized
      across tasks. Weights were measured by binary logistic regression between
      stimulus values that were sampled from Gaussian distributions and listeners'
      responses. The first task was interaural time discrimination in which listeners
      judged the laterality of the target component. The second task was monaural level
      discrimination in which listeners indicated whether the level of the target
      component decreased or increased across two intervals. For both experiments, each
      of the three components served as the target. Ten listeners participated in both
      experiments. The results showed that those individuals who adjusted perceptual
      weights in the interaural time experiment could also do so in the monaural level
      discrimination task. The fact that the same individuals appeared to be analytic
      in both tasks is an indication that the weights measure the ability to attend to
      a particular region of the spectrum while ignoring other spectral regions.

PMID- 15957777
TI  - Speech intelligibility and spatial release from masking in young children.
AB  - Children between the ages of 4 and 7 and adults were tested in free field on
      speech intelligibility using a four-alternative forced choice paradigm with
      spondees. Target speech was presented from front (0 degrees); speech or modulated
      speech-shaped-noise competitors were either in front or on the right (90
      degrees). Speech reception thresholds were measured adaptively using a three
      down/one-up algorithm. The primary difference between children and adults was
      seen in elevated thresholds in children in quiet and in all masked conditions.
      For both age groups, masking was greater with the speech-noise versus speech
      competitor and with two versus one competitor(s). Masking was also greater when
      the competitors were located in front compared with the right. The amount of
      masking did not differ across the two age groups. Spatial release from masking
      was similar in the two age groups, except for in the one-speech condition, when
      it was greater in children than adults. These findings suggest that, similar to
      adults, young children are able to utilize spatial and/or head shadow cues to
      segregate sounds in noisy environments. The potential utility of the measures
      used here for studying hearing-impaired children is also discussed.

PMID- 15957778
TI  - Localizing nearby sound sources in a classroom: binaural room impulse responses.
AB  - Binaural room impulse responses (BRIRs) were measured in a classroom for sources
      at different azimuths and distances (up to 1 m) relative to a manikin located in
      four positions in a classroom. When the listener is far from all walls,
      reverberant energy distorts signal magnitude and phase independently at each
      frequency, altering monaural spectral cues, interaural phase differences, and
      interaural level differences. For the tested conditions, systematic distortion
      (comb-filtering) from an early intense reflection is only evident when a listener
      is very close to a wall, and then only in the ear facing the wall. Especially for
      a nearby source, interaural cues grow less reliable with increasing source
      laterality and monaural spectral cues are less reliable in the ear farther from
      the sound source. Reverberation reduces the magnitude of interaural level
      differences at all frequencies; however, the direct-sound interaural time
      difference can still be recovered from the BRIRs measured in these experiments.
      Results suggest that bias and variability in sound localization behavior may vary
      systematically with listener location in a room as well as source location
      relative to the listener, even for nearby sources where there is relatively
      little reverberant energy.

PMID- 15957779
TI  - Reduced order modeling of head related impulse responses for virtual acoustic
      displays.
AB  - This study investigated the use of reduced order head related impulse response
      (HRIR) models to improve the computational efficiency in acoustic virtual
      displays. State space models of varying order were generated from zero-elevation
      HRIRs using a singular value decomposition technique. A source identification
      experiment was conducted under anechoic conditions in which three subjects were
      required to localize sounds in the front horizontal plane. The sounds were either
      (1) real sources (emitted by individual loudspeakers in a semi-circular array),
      (2) virtual sources generated from the original HRIRs, or (3) virtual sources
      generated using reduced order state space models. All virtual sources were
      created by simultaneous activation of two loudspeakers at +/- 30 degrees using a
      virtual source imaging technique based on either the measured or modeled HRIRs.
      The errors in the perceived direction of the virtual sources generated from the
      reduced order models were compared to errors in localization using the original
      HRIRs. The results demonstrate that a very significant reduction in model size
      can be achieved without significantly affecting the fidelity of the virtual
      display of horizontally placed sources.

PMID- 15957780
TI  - Pitch ranking ability of cochlear implant recipients: a comparison of sound
      processing strategies.
AB  - Pitch ranking of sung vowel stimuli, separated in fundamental frequency (F0) by
      half an octave, was measured with a group of eleven Nucleus 24 cochlear implant
      recipients using different sound coding strategies. In three consecutive studies,
      either two or three different sound coding strategies were compared to the
      Advanced Combinational Encoder (ACE) strategy. These strategies included
      Continuous Interleaved Sampling (CIS), Peak Derived Timing (PDT), Modulation
      Depth Enhancement (MDE), F0 Synchronized ACE (FOSync), and Multi-channel Envelope
      Modulation (MEM), the last four being experimental strategies. While pitch
      ranking results on average were poor compared to those expected for most normal
      hearing listeners, significantly higher scores were obtained using the MEM, MDE,
      and FOSync strategies compared to ACE. These strategies enhanced coding of
      temporal F0 cues by providing deeper modulation cues to F0 coincidentally in time
      across all activated electrodes. In the final study, speech recognition tests
      were also conducted using ACE, CIS, MDE, and MEM. Similar results among all
      strategies were obtained for word tests in quiet and between ACE and MEM for
      sentence tests in noise. These findings demonstrate that strategies such as MEM
      may aid perception of pitch and still adequately code segmental speech features
      as per existing coding strategies.

PMID- 15957781
TI  - Temporal onset-order discrimination through the tactual sense.
AB  - Tactual temporal-onset order thresholds were measured for two sinusoidal
      vibrations of different frequencies delivered to two separate locations (thumb
      and index finger) of a multi-finger tactual stimulating device. The frequency
      delivered to the thumb was fixed at 50 Hz and that to the index finger at 250 Hz.
      The amplitude and duration of each of the two sinusoidal vibrations were roved
      independently from trial to trial in a 1-interval, 2AFC procedure. Performance,
      measured as a function of stimulus-onset asynchrony (SOA), indicated that the
      temporal-onset-order threshold averaged 34 ms across four subjects. The data were
      further classified into subsets according to both the amplitude and duration of
      the two stimuli in each trial of the roving-discrimination paradigm. The results
      indicated that the amplitude differences of the two stimuli in each trial had a
      substantial effect on onset-order discrimination, while duration differences
      generally had little effect. The effects of amplitude differences are explained
      qualitatively in terms of amplitude latency relationships and stimulus
      interactions such as temporal masking. Overall, the results not only contribute
      to an enhanced understanding of the temporal sensitivity of the tactual system
      but also provide guidelines for the design of tactual aids for hearing-impaired
      persons.

PMID- 15957782
TI  - Auditory perception of sound source velocity.
AB  - In this study we investigate the perception of the velocity of linearly moving
      sound sources passing in front of a listener. The binaural simulation of motion
      used in two psychoacoustical experiments includes changes in the overall sound
      pressure level, the Doppler effect, and changes in interaural time differences.
      These changes are considered as cues for the perception of velocity. The present
      experiments are an extension of the experiments performed by Lutfi and Wang [J.
      Acoust. Soc. Am. 106, 919-928 (1999)]. The results of Experiment I show that the
      differential velocity threshold is independent of the reference velocity (10, 20,
      30, and 40 m/s), varying across listeners from 1.5 to 4.6 m/s. In Experiment II,
      a method based on the successive elimination of cues in compared pairs of signals
      was employed to estimate the weights of potential cues for velocity
      discrimination. The magnitudes of all underlying cues at thresholds are reported.
      The experimental results show the subject's preference for the Doppler cue and a
      weakest sensitivity to the cue related with interaural time differences. Finally,
      it was found that spatial differences in the source location at the endpoints of
      the motion trajectory are not a significant factor in the velocity discrimination
      task.

PMID- 15957783
TI  - Sensory and nonsensory influences on children's performance of dichotic pitch
      perception tasks.
AB  - Dichotic pitch perception reflects the auditory system's use of binaural cues to
      perceptually separate different sound sources and to determine the spatial
      location of sounds. Several studies were conducted to identify factors that
      influence children's dichotic pitch perception thresholds. An initial study of
      school children revealed an age-related improvement in thresholds for
      lateralizing dichotic pitch tones. In subsequent studies potential sensory and
      nonsensory limitations on young children's performance of dichotic pitch
      lateralization tasks were examined. A training study showed that with sufficient
      practice, young children lateralize dichotic pitch stimuli as well as adults,
      indicating an age difference in perceptual learning of the lateralization task.
      Changing the task requirements so that young children made a judgment about the
      pitch of dichotic pitch tones, rather than the spatial location of the tones,
      also resulted in significantly better thresholds. These findings indicate that
      nonsensory factors limit young children's performance of dichotic pitch tasks.

PMID- 15957784
TI  - Comparison between distortion product otoacoustic emissions and nerve fiber
      responses from the basilar papilla of the frog.
AB  - The basilar papilla (BP) is one of the three end organs in the frog inner ear
      that is sensitive to airborne sound. Its anatomy and physiology are unique among
      all classes of vertebrates. Essentially, the BP functions as a single auditory
      filter presumably arising from a mechanically-tuned mechanism. As such, both
      neural and distortion product otoacoustic emission (DPOAE) tuning may reflect a
      single mechanical filtering mechanism. Using the Duffing oscillator as a simple
      model for both neural and DPOAE tuning from the BP, two predictions can be made:
      [1] the characteristic frequency (CF) of neural tuning and the best frequency
      (BF) of DPOAE tuning will coincide and [2] the neural tuning curve and DPOAE
      audiogram have a similar shape when the neural tuning curve is scaled by a factor
      of 4 along the y-axis. We recorded both neural tuning curves and DPOAE-audiograms
      from the BP of the leopard frog. These recordings show good agreement with the
      model predictions when the stimulus tones are related by relatively small
      stimulus frequency ratios. For larger stimulus frequency ratios, DPOAE recordings
      clearly deviate from model predictions. These differences are most likely caused
      by the oversimplified representation of the frog BP by the model.

PMID- 15957785
TI  - Medial surface dynamics of an in vivo canine vocal fold during phonation.
AB  - Quantitative measurement of the medial surface dynamics of the vocal folds is
      important for understanding how sound is generated within the larynx. Building
      upon previous excised hemilarynx studies, the present study extended the
      hemilarynx methodology to the in vivo canine larynx. Through use of an in vivo
      model, the medial surface dynamics of the vocal fold were examined as a function
      of active thyroarytenoid muscle contraction. Data were collected using high-speed
      digital imaging at a sampling frequency of 2000 Hz, and a spatial resolution of
      1024 x 1024 pixels. Chest-like and fry-like vibrations were observed, but could
      not be distinguished based on the input stimulation current to the recurrent
      laryngeal nerve. The subglottal pressure did distinguish the registers, as did an
      estimate of the thyroarytenoid muscle activity. Upon quantification of the three
      dimensional motion, the method of Empirical Eigenfunctions was used to extract
      the underlying modes of vibration, and to investigate mechanisms of sustained
      oscillation. Results were compared with previous findings from excised larynx
      experiments and theoretical models.

PMID- 15957786
TI  - A flow waveform-matched low-dimensional glottal model based on physical
      knowledge.
AB  - The purpose of this study is to explore the possibility for physically based
      mathematical models of the voice source to accurately reproduce inverse filtered
      glottal volume-velocity waveforms. A low-dimensional, self-oscillating model of
      the glottal source with waveform-matching properties is proposed. The model
      relies on a lumped mechano-aerodynamic scheme loosely inspired by the one- and
      multimass lumped models. The vocal folds are represented by a single mechanical
      resonator and a propagation line which takes into account the vertical phase
      differences. The vocal-fold displacement is coupled to the glottal flow by means
      of an aerodynamic driving block which includes a general parametric nonlinear
      component. The principal characteristics of the flow-induced oscillations are
      retained, and the overall model is able to match inverse-filtered glottal flow
      signals. The method offers in principle the possibility of performing
      transformations of the glottal flow by acting on the physiologically based
      parameters of the model. This is a desirable property, e.g., for speech synthesis
      applications. The model was tested on a data set which included inverse-filtered
      glottal flow waveforms of different characteristics. The results demonstrate the
      possibility of reproducing natural speech waveforms with high accuracy, and of
      controlling important characteristics of the synthesis such as pitch.

PMID- 15957787
TI  - A modeling investigation of articulatory variability and acoustic stability
      during American English /r/ production.
AB  - This paper investigates the functional relationship between articulatory
      variability and stability of acoustic cues during American English /r/
      production. The analysis of articulatory movement data on seven subjects shows
      that the extent of intrasubject articulatory variability along any given
      articulatory direction is strongly and inversely related to a measure of acoustic
      stability (the extent of acoustic variation that displacing the articulators in
      this direction would produce). The presence and direction of this relationship is
      consistent with a speech motor control mechanism that uses a third formant
      frequency (F3) target; i.e., the final articulatory variability is lower for
      those articulatory directions most relevant to determining the F3 value. In
      contrast, no consistent relationship across speakers and phonetic contexts was
      found between hypothesized vocal-tract target variables and articulatory
      variability. Furthermore, simulations of two speakers' productions using the DIVA
      model of speech production, in conjunction with a novel speaker-specific vocal
      tract model derived from magnetic resonance imaging data, mimic the observed
      range of articulatory gestures for each subject, while exhibiting the same
      articulatory/acoustic relations as those observed experimentally. Overall these
      results provide evidence for a common control scheme that utilizes an acoustic,
      rather than articulatory, target specification for American English /r/.

PMID- 15957788
TI  - Two-dimensional model of vocal fold vibration for sound synthesis of voice and
      soprano singing.
AB  - Voiced sounds were simulated with a computer model of the vocal fold composed of
      a single mass vibrating both parallel and perpendicular to the airflow.
      Similarities with the two-mass model are found in the amplitudes of the glottal
      area and the glottal volume flow velocity, the variation in the volume flow
      waveform with the vocal tract shape, and the dependence of the oscillation
      amplitude upon the average opening area of the glottis, among other similar
      features. A few dissimilarities are also found in the more symmetric glottal and
      volume flow waveforms in the rising and falling phases. The major improvement of
      the present model over the two-mass model is that it yields a smooth transition
      between oscillations with an inductive load and a capacitive load of the vocal
      tract with no sudden jumps in the vibration frequency. Self-excitation is
      possible both below and above the first formant frequency of the vocal tract. By
      taking advantage of the wider continuous frequency range, the two-dimensional
      model can successfully be applied to the sound synthesis of a high-pitched
      soprano singing, where the fundamental frequency sometimes exceeds the first
      formant frequency.

PMID- 15957789
TI  - The effects of tones on speaking frequency and intensity ranges in Mandarin and
      Min dialects.
AB  - The differences of speaking frequency and intensity in different tonal dialects
      has not been widely investigated. The purposes of this study were (1) to compare
      the speaking frequency and speaking intensity ranges of Mandarin and Min and (2)
      to compare the speaking frequency and intensity ranges of Mandarin and Min to
      those of American English. The subjects were 80 normal Taiwanese adults divided
      into two dialect groups, Mandarin and Min. The speaking F0, the highest speaking
      F0, the lowest speaking F0, the maximum range of speaking F0, and the intensity
      counterpart were obtained from reading in their native dialects. Statistical
      analysis revealed that Min speakers had a significantly greater maximum range of
      speaking intensity and a smaller lowest speaking intensity than Mandarin
      speakers, which indicated tonal effects by speakers of the Min dialect. Moreover,
      Mandarin and Min speakers had a greater maximum range of speaking F0 and maximum
      range of speaking intensity than American English speakers. The data may provide
      an assessment tool for Mandarin speakers and Min speakers.

PMID- 15957790
TI  - A parametric model of the vocal tract area function for vowel and consonant
      simulation.
AB  - A model of the vocal-tract area function is described that consists of four
      tiers. The first tier is a vowel substrate defined by a system of spatial
      eigenmodes and a neutral area function determined from MRI-based vocal-tract
      data. The input parameters to the first tier are coefficient values that, when
      multiplied by the appropriate eigenmode and added to the neutral area function,
      construct a desired vowel. The second tier consists of a consonant shaping
      function defined along the length of the vocal tract that can be used to modify
      the vowel substrate such that a constriction is formed. Input parameters consist
      of the location, area, and range of the constriction. Location and area roughly
      correspond to the standard phonetic specifications of place and degree of
      constriction, whereas the range defines the amount of vocal-tract length over
      which the constriction will influence the tract shape. The third tier allows
      length modifications for articulatory maneuvers such as lip rounding/spreading
      and larynx lowering/raising. Finally, the fourth tier provides control of the
      level of acoustic coupling of the vocal tract to the nasal tract. All parameters
      can be specified either as static or time varying, which allows for multiple
      levels of coarticulation or coproduction.

PMID- 15957792
TI  - The effect of inharmonic partials on pitch of piano tones.
AB  - Piano tones have partials whose frequencies are sharp relative to harmonic
      values. A listening test was conducted to determine the effect of inharmonicity
      on pitch for piano tones in the lowest three octaves of a piano. Nine real tones
      from the lowest three octaves of a piano were analyzed to obtain frequencies,
      relative amplitudes, and decay rates of their partials. Synthetic inharmonic
      tones were produced from these results. Synthetic harmonic tones, each with a
      twelfth of a semitone increase in the fundamental, were also produced. A jury of
      21 listeners matched the pitch of each synthetic inharmonic tone to one of the
      synthetic harmonic tones. The effect of the inharmonicity on pitch was determined
      from an average of the listeners' results. For the nine synthetic piano tones
      studied, pitch increase ranged from approximately two and a half semitones at low
      fundamental frequencies to an eighth of a semitone at higher fundamental
      frequencies.

PMID- 15957791
TI  - Relative contributions of spectral and temporal cues for phoneme recognition.
AB  - Cochlear implants provide users with limited spectral and temporal information.
      In this study, the amount of spectral and temporal information was systematically
      varied through simulations of cochlear implant processors using a noise-excited
      vocoder. Spectral information was controlled by varying the number of channels
      between 1 and 16, and temporal information was controlled by varying the lowpass
      cutoff frequencies of the envelope extractors from 1 to 512 Hz. Consonants and
      vowels processed using those conditions were presented to seven normal-hearing
      native-English-speaking listeners for identification. The results demonstrated
      that both spectral and temporal cues were important for consonant and vowel
      recognition with the spectral cues having a greater effect than the temporal cues
      for the ranges of numbers of channels and lowpass cutoff frequencies tested. The
      lowpass cutoff for asymptotic performance in consonant and vowel recognition was
      16 and 4 Hz, respectively. The number of channels at which performance plateaued
      for consonants and vowels was 8 and 12, respectively. Within the above-mentioned
      ranges of lowpass cutoff frequency and number of channels, the temporal and
      spectral cues showed a tradeoff for phoneme recognition. Information transfer
      analyses showed different relative contributions of spectral and temporal cues in
      the perception of various phonetic/acoustic features.

PMID- 15957793
TI  - A theoretical study of the feasibility of acoustical tweezers: ray acoustics
      approach.
AB  - The optical tweezer has been found to have many biomedical applications in
      trapping macromolecules and cells. For the trapping mechanism, there has to be a
      sharp spatial change in axial optical intensity and the particle size must be
      much greater than the wavelength. Similar phenomenon may exist in acoustics. This
      work was undertaken to demonstrate theoretically that it is possible to
      acoustically trap particles near the focal point where most of the acoustic
      energy is concentrated if certain conditions are met. Acoustic force exerted on a
      fluid particle in ultrasonic fields is analyzed in a ray acoustics regime where
      the wavelength of acoustic beam is much smaller than the size of the particle. In
      order to apply the acoustical tweezer to manipulating macromolecules and cells
      whose size is in the order of a few microns or less, a prerequisite is that the
      ultrasound wavelength has to be much smaller than a few microns. In this paper,
      the analysis is therefore based on the field pattern produced by a strongly
      focused 100 MHz ultrasonic transducer with Gaussian intensity distribution. For
      the realization of acoustic trapping, negative axial radiation force has to be
      generated to pull a particle towards a focus. The fat particle considered for
      acoustic trapping in this paper has an acoustic impedance of 1.4 MRayls. The
      magnitude of the acoustic axial radiation force that has been calculated as the
      size of the fat particle is varied from 8lambda to 14lambda. In addition, both
      Fresnel coefficients at various positions are also calculated to assess the
      interaction of reflection and refraction and their relative contribution to the
      effect of the acoustical tweezer. The simulation results show that the
      feasibility of the acoustical tweezer depends on both the degree of acoustic
      impedance mismatch and the degree of focusing relative to the particle size.

PMID- 15957794
TI  - Effect of pulse characteristics on temperature rise due to ultrasound absorption
      at a bone/soft-tissue interface.
AB  - The transient temperature rise at a bone/soft-tissue interface is an important
      quantity in the safety evaluation of procedures involving trains of high
      intensity ultrasound pulses. Mathematical models based upon the time-averaged
      intensity of the pulse train can provide rapid estimates of the temperature rise,
      but are known to underestimate the temperature rise during the on-time of the
      pulse. This paper extends a previous analytical model to account for pulse shape,
      and provides error estimates for simulations employing time-averaged intensities.
      A simple analytic expression for the interface temperature that accounts for both
      bone and soft-tissue properties is provided. The analytic expression agrees well
      with temperature rise predictions based upon the finite-element method, when the
      insonation time is large compared to the pulse repetition period. In this case of
      large relative insonation time, the pulse shape is found to be inconsequential.

PMID- 15957795
TI  - Echolocation signals of the free-ranging Yangtze finless porpoise (Neophocaena
      phocaenoides asiaeorientialis).
AB  - This paper describes the high-frequency echolocation signals from free-ranging
      Yangtze finless porpoise in the Tian-e-zhou Baiji National Natural Reserve in
      Hubei Province, China. Signal analysis showed that the Yangtze finless porpoise
      clicks are typical high-frequency narrow-band (relative width of the frequency
      spectrum Q = 6.6 +/- 1.56, N = 548) ultrasonic pulses. The peak frequencies of
      the typical clicks range from 87 to 145 kHz with an average of 125 +/- 6.92 kHz.
      The durations range from 30 to 122 micros with an average of 68 +/- 14.12, as.
      The characteristics of the signals are similar to those of other members of the
      Phocoenidae as well as the distantly related delphinids, Cephalorhynchus spp.
      Comparison of these signals to those of the baiji (Lipotes vexillifer), who
      occupies habitat similar to that of the Yangtze finless porpoise, showed that the
      peak frequencies of clicks produced by the Yangtze finless porpoise are
      remarkably higher than those produced by the baiji. Difference in peak frequency
      between the two species is probably linked to the different size of preferred
      prey fish. Clear double-pulse and multi-pulse reverberation structures of clicks
      are noticed, and there is no indication of any low-frequency (< 70 kHz)
      components during the recording period.

PMID- 15957796
TI  - Sound production by North Atlantic right whales (Eubalaena glacialis) in surface
      active groups.
AB  - The surface active group (SAG) is the most commonly observed surface social
      behavior of North Atlantic right whales. Recordings were made from 52 SAGs in the
      Bay of Fundy, Canada between July and September, from 1999 to 2002. The call
      types recorded from these groups were similar to those described previously for
      Southern right whales (Eubalaena australis), with six major call types being
      termed scream, gunshot, blow, upcall, warble, and downcall. The percentage of
      total calls of each call type depended on the group size and composition. The
      most common call type recorded was the scream call. The scream calls were
      produced by the focal female in a SAG. Production of other sound types can be
      attributed to whales other than the focal female, with gunshot and upcalls
      produced by males, and warble calls produced by female calves. The source levels
      for these sounds range from 137 to 162 dB rms re 1 ,tPa-m for tonal calls and 174
      to 192 dB rms for broadband gunshot sounds.

PMID- 15957797
TI  - Optimization of angular and frequency compounding in ultrasonic attenuation
      estimations.
AB  - Previous reports have shown that the variance in ultrasound attenuation
      measurements is reduced when spatial and frequency compounding were applied in
      data acquisition and analysis. This paper investigates factors affecting the
      efficiency of compound attenuation imaging methods. A theoretical expression is
      derived that predicts the correlation between attenuation versus frequency slope
      (beta) estimates as a function of the increment between measurement frequencies
      (deltaf ) and the angular separation between beam lines (Delta (theta)).
      Theoretical results are compared with those from attenuation measurements on
      tissue-mimicking phantoms and from simulation data. Both predictions and
      measurement results show that the correlation between beta estimates as a
      function of (Delta f ) is independent of the length of the radio frequency (rf)
      data segment over which beta is derived. However, it decreases with an increase
      in the length of the data segment used in power spectra estimates. In contrast,
      the correlation between beta estimates as a function of delta(theta) decreases
      when the rf data segment length is longer or the frequency of the signal is
      higher. O 2005 Acoustical Society of America.

PMID- 15957798
TI  - Comparison of measurements of phase velocity in human calcaneus to Biot theory.
AB  - Biot's theory for elastic propagation in porous media has previously been shown
      to be useful for modeling the dependence of phase velocity on porosity in bovine
      cancellous bone in vitro. In the present study, Biot's theory is applied to
      measurements of porosity-dependent phase velocity in 53 human calcanea in vitro.
      Porosity was measured using microcomputed tomography for some samples (n = 23)
      and estimated based on bone mineral densitometry for the remaining samples (n =
      30). The phase velocity at 500 kHz was measured in a water tank using a through
      transmission technique. Biot's theory performed well for the prediction of the
      dependence of sound speed on porosity. The trend was quasilinear, but both the
      theory and experiment show similar slight curvature. The root mean square error
      (RMSE) of predicted versus measured sound speed was 15.8 m/s.

PMID- 15957799
TI  - Off-axis sonar beam pattern of free-ranging finless porpoises measured by a
      stereo pulse event data logger.
AB  - The off-axis sonar beam patterns of eight free-ranging finless porpoises were
      measured using attached data logger systems. The transmitted sound pressure level
      at each beam angle was calculated from the animal's body angle, the water surface
      echo level, and the swimming depth. The beam pattern of the off-axis signals
      between 45 degrees and 115 degrees (where 0 degrees corresponds to the on-axis
      direction) was nearly constant. The sound pressure level of the off-axis signals
      reached 162 dB re 1 microPa peak-to-peak. The surface echo level received at the
      animal was over 140 dB, much higher than the auditory threshold level of small
      odontocetes. Finless porpoises are estimated to be able to receive the surface
      echoes of off-axis signals even at 50-m depth. Shallow water systems (less than
      50-m depth) are the dominant habitat of both oceanic and freshwater populations
      of this species. Surface echoes may provide porpoises not only with diving depth
      information but also with information about surface direction and location of
      obstacles (including prey items) outside the on-axis sector of the sonar beam.

PMID- 15957800
TI  - [Journal "Vestnik Khirurgii named after Grekov" is 120 years old].

PMID- 15957801
TI  - [Ivan Ivanovich Grekov (1867-1934)].

PMID- 15957802
TI  - [The ways of the development of clinical medicine in the XXI century].
AB  - The article raises a question of the passion by many doctors for treating the
      patients with a great number of medicines. Recommendations on the medicine-free
      therapy are given which include giving up harmful habits and on healthy mode of
      life.

PMID- 15957803
TI  - [Special surgical treatment of patients with nodular tumors of the thyroid gland
      against the background of diffuse toxic goiter].
AB  - The authors have analyzed the results of treatment of 147 patients with diffuse
      toxic goiter (DTG) operated upon in the St. Petersburg Center of the surgery of
      the endocrine system organs. Questions of surgical strategy are considered when
      DTG is combined with nodular forms. The diagnostic potentialities of the methods
      used are assessed. The incidence of carcinomas in patients with nodular
      formations and DTG was determined. It was shown that the presence of nodules in
      the thyroid gland did not influence the nearest and distant results when using
      the corresponding surgical strategy.

PMID- 15957804
TI  - [Neurohumoral changes in acute intestinal obstruction].
AB  - Neurohumoral changes were studied in 431 patients with acute intestinal
      obstruction and in experiments in 165 small laboratory animals with the model of
      small intestine ileus. The results were obtained on the basis of estimation of
      the concentration of catecholamines, acetylcholine-like substances, serotonine,
      histamine, their metabolism products in blood plasma and of the
      cardiointervalography data. The neurohumoral changes were shown to appear as
      early as the initial stage of the disease and to be progressing when the disease
      period became longer. The prevailing sympathetic activity was dependent on the
      decreased acetylcholine-like substances in blood plasma and tissues. The
      serotonine and histamine metabolism changed depending on the stage of the
      disease.

PMID- 15957805
TI  - [Method of preparing a low-diaphragm flap].
AB  - Diaphragm flaps on the low diaphragm vessels cut by the method described were
      used in 39 patients for plasty of the stump of the main and lobe bronchus,
      tracheo-bronchial and inter-bronchial anastomosis, pericardium. In 38 (97.4%) out
      of 39 patients the diaphragm plasty proved to be effective, the mechanical and
      biological characteristics of the flap allowed the desired effect of plasty to be
      obtained. The method of cutting the low diaphragm flap used is simple, safe and
      allows the preparation of a good plasty material for different purposes in the
      thoracic surgery.

PMID- 15957806
TI  - [Specific topographic-anatomical and technical features of resection of the
      stomach by the Roux method].
AB  - The topographic-anatomical investigations of the extraorganic part of the
      arterial and nervous systems of the duodenum and the initial part of the jejunum
      in combination with the results of the clinical use of gastric resection by the
      Roux method allowed to draw a conclusion that the development of Roux syndrome
      can be prevented by a transection of the jejunum with the saved arcades between
      the first jejunal artery, the duodenal branch and the second jejunal arteries.
      The rules of gastric resection by the Roux method and indications to this
      procedures in patients with ulcer disease of the stomach and duodenum are
      described. Good and excellent long-term results were obtained in 75.8% of the
      patients operated upon.

PMID- 15957807
TI  - [The endoscopic treatment of bronchial fistulas by submucosal injections].
AB  - A total of 21 patients (aged 30-72) with bronchial stump fistulas (307 mm) were
      treated by a newly developed method of treatment of purulent-destructive
      pulmonary diseases. This technique represents a gradual narrowing of the
      bronchial fistula lumen due to infiltrate formation in the submucosal bronchial
      layer. The volume formation substance biopolymer "DAM+", hydrogenous biopolymer
      with ions of silver "Argiform" for endoprosthesis of the soft tissues, is
      injected into the submucosal bronchial layer. It is necessary to make 5-20
      fibrobronchoscopies for bronchial fistula healing. No complications occurred as a
      result of this treatment. The healing of bronchial fistula and bronchial stump
      epithelization were found in 18 patients.

PMID- 15957808
TI  - [Surgical treatment of severe forms of metabolic syndrome].
AB  - The authors analyze the components of the metabolic syndrome in patients with
      morbid obesity treated at the surgical department. The effects of a modified
      operation of jejunal-ileal shunt on the components of the metabolic syndrome were
      shown in 220 patients operated upon at the clinic of Faculty surgery of the
      Pavlov Medical Academy in St. Petersburg. The indications to the operative
      treatment of the metabolic syndrome were substantiated on the basis of
      etiopathogenesis. The estimation of long-term results of the operation of jejunal
      ileal shunt in patients with the metabolic syndrome is given.

PMID- 15957810
TI  - [Prognosis of the severity of acute pancreatitis by the neural network method].
AB  - For prognozing the character of the development of acute pancreatitis a neural
      network of the direct spread of the signal was developed with 15 inlets, 5
      neurons of the latent layer and two outlets. The network was trained with the
      help of an algorithm of an inverse spread of the error. The sensitivity of the
      produced prognostic model was 100%, specificity at admission--70%, on the first
      day--80%, on the second and third day--90%. Before the moment of hospitalization
      57 patients were observed during 72 hours. The diagnosis was confirmed in all
      cases by the methods of computed tomography with contrast amplification.

PMID- 15957809
TI  - [Clinico-morphological characteristics of the methods of connection of the
      postoperative wound edges].
AB  - The decision for the method of connection of the skin wound edges should be based
      on specific reconstruction of the injured tissues depending on the suture
      material and kind of the skin suture. An alternative of the classical suturing of
      the postoperative wound is a sutureless fixation of the skin edges--a method of
      using adhesive plaster. The work includes a clinico-morphological comparison of
      the course of the process of regeneration when using the intracutaneous suture
      and the adhesive plaster. The macroscopic and pathologic-histological estimation
      of the healing of the postoperative wound of the skin has shown that a smoother
      course of the postoperative period is noted in the groups where the adhesive
      plaster was used.

PMID- 15957811
TI  - [Modern ideas on the treatment of dislocations and fracture-dislocations in the
      elbow joint].
AB  - The authors describe the causes and surgical methods of treatment of fresh and
      long-standing dislocations and fracture-dislocations in the elbow joint. The
      indications to using different operative methods and technical-surgical
      interventions are described in details as well as long-term results of treatment
      by the literature data. The current methods and the authors' methods of
      prophylactics and treatment of postoperative complications are analyzed. The
      methods of rehabilitation of such patients are also described.

PMID- 15957812
TI  - [Replacement of the urinary bladder by the stomach body].
AB  - In the period from 2001 through 2004 plasty of the urinary bladder was performed
      in 24 patients using a. et v. gastroepyploici dexter. Mean age of the patients
      (18 men and 6 women) was 58.2 years. Gastrocystoplasty in 18 patients was
      performed after radical cystectomy for urinary bladder cancer, in 6 patients for
      neurogenic and small urinary bladder. The authors' original modification with a
      complete transversal resection of the stomach body taken together with the lesser
      curvature was used in operations on 10 patients. Early postoperative
      complications developed in one patient, late ones--in two patients, there were no
      lethal outcomes. Positive functional results were noted in all patients within
      the terms of observations from 2 through 22 months. Good quality of life was
      noted in all of them.

PMID- 15957813
TI  - [Hemodynamic reaction attended safety in severe head injury patients at different
      periods of operative treatment].
AB  - The safety of hemodynamic reactions were studied at the stages of operative
      treatment of patients with severe cranio-cerebral traumas (CCT) during anesthesia
      using alfa-2 adrenoagonist Clofelin and opioid analgetic Fentanyl and basal
      hypnotics Propofol and sodium Thiopental. It was shown that the using of these
      techniques of anesthesia in CCT patients is followed by a formation of a
      sufficient and physiologically justified level of neurovegetative stabilization.
      It facilitates a coordinated work of the mechanisms of auto-regulation of blood
      circulation responsible for the maintenance of stable tissue perfusion at all
      steps of operations.

PMID- 15957814
TI  - [Effects of induction of anesthesia on hemodynamics in children with deformities
      of the spinal cord when turning to the position lying on the belly].
AB  - The investigation was devoted to assessment of the reaction of blood circulation
      to turning to the position "lying on the belly" in different variants of
      induction of anesthesia to children aged from 7 to 17 years having deformities of
      the spinal cord. The following combinations were compared: Ketamin, Fentanyl, and
      inhalation with nitrous oxide; Propofol and Fentanyl; Thiopental, Clofelin,
      Fentanyl and inhalation with nitrous oxide; Propofol, Clofelin and Fentanyl. The
      minimal changes in blood circulation were found to occur when using the
      combination of Thiopental, Clofelin and Fentanyl.

PMID- 15957815
TI  - [Minimally invasive surgery of acute superficial varicothrombophlebitis in
      patients having somatic contraindication to venectomy].
AB  - An analysis was made of complex examination and the following treatment of 21
      patients with acute superficial varicothrombophlebitis who had some pronounced
      pathology of internal organs preventing radical treatment. An original technology
      of treatment of varicothrombophlebitis developed by the authors includes
      crossectomy, truncal catheter sclerotherapy up to the place of thrombosis of the
      subcutaneous veins, stage-wise phlebocentesis of the thrombosed veins followed by
      injectional sclerotherapy with the ultrasonic control. The thrombophlebitis
      phenomena were arrested in all patients. In addition, the clinical manifestations
      of chronic venous insufficiency were regressed in the postoperative period.

PMID- 15957816
TI  - [Surgical treatment of lung cancer patients with brain metastases].
AB  - The authors present an experience with diagnosing and treatment of 16 patients
      suffering from lung cancer with solitary metastasis into the brain. The
      examination performed has shown that in 7 out of 16 patients the surgical
      treatment was found to be not expedient. This solution was based on the detection
      of an extensive spread of lung cancer: multiple metastasis outside the thoracic
      cavity and the brain or inside the brain, and in one case--due to a considerable
      reduction of indices of the functional and reserve capacities of respiration and
      blood circulation. Single-step operations were carried out in 9 patients with
      lung cancer with a solitary metastasis into the brain (resection of the lung with
      an ablation of the brain metastasis). Out of the 9 patients operated on 6
      patients survived for as long as 1.5 to 2 years, one patient lived longer than 4
      years. Two other patients operated upon in June 2003 and March 2004 are still
      alive and feel much better. Satisfactory results of treatment of these patients
      show such methods to be expedient.

PMID- 15957817
TI  - [Combined treatment of glyal and metastatic tumors of the brain].
AB  - Combined treatment of glyal and metastatic tumors of the brain allows
      prolongation of survival with the saved high physical and social level of the
      patients following the algorithm of the treatments: operative intervention with
      the minimal injury of the brain substance and preservation of all functionally
      important zones; chemotherapy with nitrosourea with the preferable bringing to
      the tumor zone; exposure to radiation.

PMID- 15957818
TI  - [Certain aspects of the present-day diagnosis and treatment of iliopsoitis].
AB  - MR-tomography is known to be a valuable method of investigation. It allows to get
      a picture of thin layers of the human body in any section. In addition, it
      facilitates the diagnosis of inflammatory alterations to the muscles of the
      retroperitoneal space before the development of purulent phases of inflammation.
      The difficulties of the diagnosis of pyo-inflammatory diseases are leveled due to
      practical possibility of MRT to detect the inflammation focus.

PMID- 15957819
TI  - [Treatment of tumoral colonic obstruction].
AB  - The work was devoted to problems of treatment of patients with cancer of the
      colon complicated by tumoral colonic obstruction. The authors propose an improved
      clinical classification of disturbances of colonic obstruction with colorectal
      cancer. The questions discussed are: decision on the strategy of treatment of
      acute colonic obstruction patients, the possible differential approach to
      choosing methods of treatment depending on localization of tumor and duration of
      the period of the development of intestinal obstruction. The results of treatment
      of 148 patients with colorectal cancer complicated by acute colonic obstruction
      are analyzed. It was shown that in 20% of patients with the initial stage of
      obstruction with the tumor localized in the left half of the colon it was
      possible to resolve the obstruction by conservative measures followed by the
      preparation of the patients to planned operation.

PMID- 15957820
TI  - [Necrotizing fasciitis].
AB  - An experience with treatment of four patients with necrotizing fasciitis (NF) and
      a review of literature were used to characterize this rare but dangerous for life
      disease, The pathogen of NF is a hemolytic group A streptococcus and anaerobes.
      The mechanism of the development of fasciitis is based on impairments in the
      microcirculatory bed due to the action on the cytokine endothelium. Rapidly
      progressing necrosis of fasciae results in a number of complications. The
      treatment consists of the early and aggressive necrectomy and intensive
      antibiotic therapy in combination with immunomodulation.

PMID- 15957821
TI  - [The role of laparoscopy in the diagnosis and treatment of early postoperative
      complications].
AB  - Results of 276 laparoscopic operations performed for diagnostic and therapeutic
      purposes in the early postoperative period in 198 patients are analyzed. All the
      patients had been previously operated on the organs of the abdominal cavity and
      retroperitoneal space: in 131 patients the investigations were performed with a
      diagnostic purpose; in 67 patients a laparoscopic method was used for treatment
      of complications of the early postoperative period. This problem can be solved by
      using the methods allowing diagnosing the complication as early as possible,
      before the development of irreversible alterations, and allowing to choose the
      most rational methods of treatment.

PMID- 15957822
TI  - [Contribution to the method of surgical correction of dumping-syndrome after
      resection of the stomach].

PMID- 15957823
TI  - [The endothelium dysfunction: principles of diagnosis and clinical significance
      in obliterating atherosclerosis of the peripheral arteries].

PMID- 15957824
TI  - [Aneurysms of the pancreaticoduodenal artery in association with stenosis or
      occlusion of the celiac trunk].
AB  - On the basis of an analysis of 69 patients including 2 personal observations the
      authors discuss the questions of pathogenesis, clinical picture, diagnosis and
      treatment of aneurysms of the pancreaticoduodenal artery in association with
      stenosis or occlusion of the celiac trunk (CT). A description of 2 cases with a
      true not broken aneurysms of the inferior pancreaticoduodenal artery and
      subocclusion of the celiac trunk is given which was caused by compression of the
      latter by the median arcuate ligament of the diaphragm and neurofibrous tissue of
      the celiac plexus. These patients were detected as a result of examinations and
      operative treatment of 556 patients with compressive stenosis of the celiac trunk
      for the period from 1982 through 2002. In one case a transcatheter embolization
      of the aneurysm was fulfilled followed in 3 months by a compression of the celiac
      trunk, in the other case a compression of the celiac trunk was made first and
      then in 5 months it was followed by resection of the aneurysm with a favorable
      outcome.

PMID- 15957825
TI  - [The impaired healing of the wounds and methods of correction].

PMID- 15957826
TI  - [General contemplation on causality deduction in appraising clinical efficacy of
      traditional Chinese medicine (continued)].

PMID- 15957827
TI  - [Clinical efficacy of compound periploca liquid in treating condyloma acuminatum
      and its effect on human papilloma virus DNA expression in vitro].
AB  - OBJECTIVE: To investigate the clinical efficacy of compound periploca liquid
      (CPL) in treating condyloma acuminatum (CA), and to explore its mechanisms at
      molecular level. METHODS: Eighty-one patients with CA were randomly divided into
      three groups, 30 patients in Group A were treated with CPL, 21 in Group B were
      treated with periploca syrup and 30 in Group C were treated with Youtuoxin (YXG).
      The clinical efficacy and adverse reaction occurred in the three groups was
      evaluated respectively. Besides, change of human papilloma virus (HPV) DNA in two
      patients with CA was determined by polymerase chain reaction (PCR) in vitro after
      being treated with CPL and periploca, the monarchic drug of CPL. RESULTS: The
      cure rate obtained in group A, B, and C was 56.67%, 42.86% and 63.33%
      respectively, the total effective rate in them was 83.33%, 71.43% and 86.67%
      respectively, the difference of therapeutic efficacy was insignificant among the
      three groups. But the adverse reaction occurrence in them (6.67%, 4.76% and
      86.67%) was significantly different (P < 0.01). The recurrent rate in them was
      14.29%, 12.5% and 47.1% respectively. PCR showed negative expression of HPV in
      the two samples of CA of same concentration after the verrucous homogenate
      suspension being treated with CPL or periploca syrup of different concentration,
      while it was positive after the suspension was treated with the group of normal
      saline without any drug. CONCLUSION: The therapeutic efficacies of CPL, periploca
      syrup and Youtuoxin are not significantly different, but the former two have
      advantages of less adverse effects and lower recurrent rate. And they are
      possibly having germicidal action on HPV-DNA in CA tissue in vitro.

PMID- 15957828
TI  - [Effect of purified xuefu capsule on ultrasonographic figures in patients with
      carotid atherosclerosis].
AB  - OBJECTIVE: To investigate the effect of Purified Xuefu Capsule (PXC) on
      ultrasonographic figures in patients with carotid atherosclerosis (CAS). METHODS:
      Ninety-two patients with CAS were randomly divided into two groups, the 45
      patients in the treated group were treated by conventional western medicine with
      additional PXC, the 47 patients in the control group were given conventional
      western medicine alone. One month's treatment was regarded as one course, and
      three courses of treatment were given successively to both groups. Carotid
      ultrasonography was performed before and after treatment, and the figures were
      compared. RESULTS: The thickness of endangium, average number of plaques, plaque
      scores, plaque volume index and length of the biggest soft plaque or mixed
      plaques, stenosis rate of vascular area, and the resistant index of blood vessels
      were decreased after treated with PXC for 3 months in the treated group. The
      differences of these indexes in the treated group before and after treatment, and
      that between the treated group and the control group after treatment were
      significant (P < 0.01). CONCLUSION: PXC can improve hemodynamics and eliminate
      atherosclerotic plaque to a certain degree, so it has definite effect for
      prevention and treatment of CAS.

PMID- 15957829
TI  - [Effect of astraglus injection on serum apoptosis relevant factors in patients
      with chronic heart failure].
AB  - OBJECTIVE: To investigate the effect of Astragalus injection (AGI) on serum
      apoptosis related factors such as soluble Fas (sFas), soluble Fas ligand (sFasL)
      and tumor necrosis factor alpha (TNF-alpha) in patients with chronic heart
      failure (CHF). METHODS: Eighty-four patients with CHF of NYHA II-IV grade were
      randomly divided into two groups, the treated group (42 patients) treated with
      AGI and the control group (42 patients) treated with routine treatment. The level
      of serum sFas, sFasL, and TNF-alpha were measured with ELISA before and after
      treatment. At the same time, patients' heart function were graded according to
      the NYHA classification and their indices of left ventricular function were
      determined. RESULTS: Patients' NYHA grade was improved in both groups after
      treatment (P < 0.05 or P < 0.01), and it was better in the treated group than
      that in the control group (P < 0.05). Moreover, in the treated group, the left
      ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume
      (LVEDV) decreased, the left ventricular ejection fraction (LVEF) increased, which
      was significantly different than that before treatment (P < 0.05) respectively;
      level of serum apoptosis related factors sFas, sFas L and TNF-alpha were
      significantly decreased after treatment, showing significant difference as
      compared with those before treatment or with those in the control group after
      treatment (P < 0.05 or P < 0.01). While all indices had no obvious change in the
      control group. CONCLUSION: AGI may be regarded as an effective remedy for
      treatment of CHF owing to its effects in decreasing the level of serum apoptosis
      related factors in patients with CHF.

PMID- 15957830
TI  - [Application of Danshen injection on early stage of renal transplantation].
AB  - OBJECTIVE: To investigate the effect of Danshen injection (DSI) on early stage of
      renal transplantation. METHODS: One hundred and twelve patients in early stage
      after renal transplantation were allocated in the treated group, they were
      treated by conventional treatment with DSI 60 ml given additionally once a day
      for 10 days. And 109 patients who received conventional treatment alone after
      renal transplantation at the corresponding period were allocated in the control
      group. Indexes in the two groups, including volume of urine, serum creatinine
      (SCr), endogenous creatinine clearance rate, incidence of delayed graft function
      and acute rejection reaction, blood viscosity (BV), platelet aggregation rate
      (PAR) as well as the blood flow resistance in graft measured by color Doppler
      ultrasonography. RESULTS: The urinary volume and endogenous creatinine clearance
      rate in the treated group were significantly higher, but levels of SCr, incidence
      of renal function recovery retardation, BV, PAR and blood flow resistance in
      graft were significantly lower than those in the control group (P < 0.05). The
      difference of incidence of acute rejection reaction between the two groups was
      insignificant (P > 0.05). CONCLUSION: DSI can improve blood microcirculation,
      decrease the incidence of renal function recovery retardation, these effects are
      helpful for recovery of renal function after renal transplantation.

PMID- 15957831
TI  - [Effect of Bushen recipe on T-cell subsets and their function in patients with
      chronic hepatitis B].
AB  - OBJECTIVE: To observe the regulatory effect of Bushen recipe (BSR) on immune
      function in patients with chronic hepatitis B. METHODS: Thirty patients with
      HBeAg+ and abnormal alanine transaminase (ALT) level were treated with BSR for 6
      months. The following parameters before treatment, 3 months and 6 months after
      treatment were tested: (1) HBV DNA by fluorescence quanitiative PCR; (2) Levels
      of interleukin-10 (IL-10) and interferon-gamma in supernatant of cultured
      peripheral blood mononuclear cell (PBMC) after had been cultured with HBeAg,
      HBcAg and phytohemagglutinin (PHA) for 48 hrs; (3) Blood levels of T-cells,
      including CD4+ , CD8+ , CD8+ CD28+ , CD8+ CD28- and CD28+ , and their ratio, as
      well as the percentage of CD8+ CD28+ in the cell culture after being co-cultured
      with PHA for 48 hrs. RESULTS: In patients effectively treated by BSR, after 3
      months treatment, level of IFN-gamma in PBMC culture significantly increased,
      CD8+ CD28+ , CD28+ T-cells significantly enhanced and IL-10 and CD8 + CD28+ T
      cells significantly decreased (P < 0.05, P < 0.01). CONCLUSION: BSR could
      significantly strengthen the expression of Th1 type cytokine, decrease the
      expression of Th2 type cytokine and promote the expression of CD8+ cytotoxic T
      lymphocyte, which may be one of mechanisms in suppressing HBV DNA replication.

PMID- 15957832
TI  - [Study on the effect of qinggan jiangtang tablet in improving the insulin
      resistance in patients with multiple metabolic syndrome].
AB  - OBJECTIVE: To observe the effect of Qinggan Jiangtang tablet (QJT) in improving
      the insulin resistance (IR) in patients with multiple metabolic syndrome (MMS).
      METHODS: Adopting randomized controlled double-blinded method, 60 patients with
      MMS were divided equally into two groups. The treated group was treated by oral
      taking of QJT 3 tabs, twice a day and the control group treated by oral taking of
      Glucophage 3 tabs, twice a day, the therapeutic course for both groups was 1
      month, and the observation lasted for 2 successive courses. RESULTS: After
      treatment, levels of blood glucose, fasting and postprandial blood glucose, C
      peptide and IR were significantly reduced with markedly improvement of beta-cell
      function in both groups, the difference between the two groups showed no
      significance. Change of plasma level of free fatty acids before and after
      treatment in both groups was insignificant. CONCLUSION: QJT has the effects on
      reducing blood glucose, blood lipids, blood pressure and IR and improving
      function of beta cells.

PMID- 15957833
TI  - [Effect of triptolide on urinary monocyte chemottractant protein-1 in patients
      with diabetic nephropathy].
AB  - OBJECTIVE: To observe the change of urinary monocyte chemottractant protein-1
      (MCP-1) in patients with diabetic nephropathy (DN), and to explore the
      therapeutic effect and mechanism of triptolide (TL) in treating DN. METHODS:
      Thirty-five patients in the treated group were treated with TL plus benazepril
      and thirty two patients in the control group were treated with benazepril alone
      for six months. The change of urinary MCP-1 was measured before and after
      treatment. RESULTS: Level of urinary MCP-1 in DN patients was significantly
      higher than that in healthy subjects (P < 0.01), but it could be significantly
      decreased after TL treatment, showing significant difference as compared with
      that in the control group (P < 0.05). CONCLUSION: Determination of urinary MCP-1
      level is beneficial to know the degree of kidney inflammation in DN patients. TL
      can inhibit inflammatory reaction to decrease the level of urinary MCP-1, and
      thus improve the renal function.

PMID- 15957834
TI  - [Preliminary clinical observation on effect of soduim ferulate in treating
      diabetic nephropathy].
AB  - OBJECTIVE: To investigate the effect of sodium ferulate (SF) on diabetic
      nephropathy (DN). METHODS: Forty-eight DN patients of early stage and 54 DN
      patients of clinical stage were randomly divided into two groups, the
      conventional treatment group and the SF treatment group. Indexes, including
      urinary albumin excretion rate (UAER), serum endothelin (ET), blood urea nitrogen
      (BUN), serum creatinine (Scr) and fasting blood glucose (FBG) were observed.
      RESULTS: The levels of UAER, BUN and ET were decreased in all DN patients, either
      early stage or clinical stage, after treated with SF for 4 weeks (P < 0.05, P <
      0.01), but changed insignificantly in those treated with conventional treatment.
      CONCLUSION: SF can decrease the levels of UAER and BUN in DN patients, the
      mechanism may relate with the decreasing of ET production and antagonizing to the
      binding of ET with its receptors.

PMID- 15957835
TI  - [Effect of shenfu injection on brain natriuretic polypeptide and aminoterminal
      peptide of precollagen type III in patients with acute myocardial infarction
      during intervention treatment].
AB  - OBJECTIVE: To investigate the effect of Shenfu injection (SFI) on indexes of
      heart function and myocardial fibrosis in patients with acute myocardial
      infarction (AMI) treated by percutaneous coronary intervention (PCI). METHODS:
      Ninety-three AMI patients treated by PCI were randomly divided into two groups,
      47 in the treatment group (treated by PCI plus 40 ml SFI intravenous injection,
      once a day for 7 days) and 46 in the control group (treated by PCI only). Levels
      of brain natriuretic poly peptide (BNP) and aminoterminal peptide of precollagen
      type III (NP III) were measured at different time points, i.e. immediately after
      admission (T1), and at 24th hour (T2) and 7th day (T3) after AMI onset in the two
      groups. RESULTS: The proportion of TIMI 3 grade of front blood flow in AMI
      related vessels after PCI was insignificantly different in the two groups. The
      concentration of BNP of T2 was significantly higher than that of T1 in the two
      groups (P < 0.01), and it was higher in the control group than that in the
      treatment group (P < 0.01), while at T3, it was insignificantly different in the
      treatment group to that of T1 (P > 0.05), but in the control group, it was still
      significantly higher than that in the treatment group and that of T1 (P < 0.01).
      The levels of NP III the two groups were similar at T1 and T2 (P > 0.05). At T3,
      it showed an increase in the treatment group, but with no significant difference
      (P > 0.05) as compared with that at T1, but in the control group did markedly
      increase and showed significant difference as compared with that of T1 and that
      in the treatment group at T3 (P < 0.05). CONCLUSION: Early applying of SFI can
      protect myocardium from ischemia/reperfusion injury after AMI, ameliorate the
      degree of injury, improve heart function of patients and prevent myocardial
      fibrosis.

PMID- 15957836
TI  - [Protective mechanisms of radix salviae miltiorrhizae against chronic alcoholic
      liver injury in mice].
AB  - OBJECTIVE: To investigate the protective mechanisms of Radix Salviae
      miltiorrhizae (RSM) on chronic alcoholic liver injury in mice. METHODS: The
      chronic alcoholic liver injury mouse model was established. The morphologic
      change of hepatic tissue was observed with hematoxylin-eosin (HE) staining; the
      levels of toll-like receptor-4 (TLR-4) mRNA in hepatic tissue and hemeoxygenase-1
      (HO-1) mRNA were determined using reverse transcription polymerase chain reaction
      (RT-PCR) technique; and the expression of TLR-4 protein was determined by
      immunohistochemistry method. RESULTS: RSM could alleviate the fatty degeneration
      and adiponecrosis of hepatic cells induced by alcohol, down-regulate the
      expressions of TLR-4 mRNA and HO-1 mRNA, and significantly decrease the number of
      TLR-4 positive cells. CONCLUSION: RSM could prevent liver injury from alcohol by
      way of influencing TLR-4 signal transcription.

PMID- 15957837
TI  - [Inhibitory effect of active fraction of tiaoxin recipe on beta-amyloid protein
      induced long-term potentiation in CA1 area of rats' hippocampal slices].
AB  - OBJECTIVE: To study the effect of the active fraction of Tiaoxin recipe (TXR-A),
      in inhibiting long-term potentiation (LTP) induced by beta amyloid protein (beta
      AP) in CA1 area of rats' hippocampal slices. METHODS: The population spike (PS)
      in CA1 area of hippocampal slices incubated in different medium was recorded
      before and after LTP was evoked by a 100 Hz, 100 trains high frequency
      stimulation (HFS), using extracellular microelectrode recording techniques.
      RESULTS: The amplitude of PS significantly decreased after HFS in hippocampal
      slices incubated in medium containing 0.2 micromol/L beta-AP for more than 1.5
      hour, as compared with that incubated in normal cerebrospinal fluid, the
      difference was significant, suggesting that beta-AP could inhibit LTP in
      hippocampal slices. The average amplitude of PS in slices incubated in beta-AP
      containing medium could be significantly enhanced by adding high-concentration
      TXR-A or TXR into the medium, and TXR-A showed a better effect of enhancing than
      that of TXR, indicating that TXR-A could increase the amplitude of LTP.
      CONCLUSION: TXR-A may be the chief ingredient extracted from TXR for improving
      beta-AP induced LTP in CA1 area of rats' hippocampus, to antagonise the
      inhibition of beta-AP on LTP is possibly one of the mechanisms for its
      intelligence benefiting action.

PMID- 15957838
TI  - [Effect of curcumin on expression of human low density lipoprotein receptors in
      Xenopus Laevis oocytes].
AB  - OBJECTIVE: To investigate the molecular mechanism of curcumin in reducing blood
      lipids by establishing gene expression system of human low density lipoprotein
      receptors (LDL-R) in Xenopus Laevis oocytes (XLO). METHODS: The expression of LDL
      R on cytomembrane was determined using immuno-fluorescent, ligand-fluorescent and
      immune colloidal gold techniques after human LDL-R containing p3.7 LDL plasmid
      was led into nucleus. And the expression of LDL-R gene in XLO was quantitatively
      determined by ELISA after being interfered with different concentrations of
      curcumin. RESULTS: The human LDL-R gene could be expressed on XLO, which could be
      significantly enhanced by curcumin in a dose-dependent manner. Conclusion One of
      the paths of curcumin in reducing blood lipids and anti-atherosclerosis was
      improving LDL-R gene expression and increasing the LDL-cholesterol absorption of
      cells.

PMID- 15957839
TI  - [Effects of cinnabar and realgar in angong niuhuang powder on lactate
      dehydrogenase and its isoenzymes in rats with infectious cerebral edema].
AB  - OBJECTIVE: To explore the pharmacologic mechanism of cinnabar (CA) and realgar
      (RG) in Angong Niuhuang powder (ANP) by way of studying the characteristics of
      their effects on organism under physiologic and pathologic states. METHODS: SD
      rats were randomly divided into six groups, 8-10 rats in each group. Group A:
      untreated normal rats; Group B: normal rats administered by ANP (drug I) 278
      mg/kg; Group C: normal rats administered by ANP subtracted CA and RG (drug II)
      222.7 mg/kg; Group D: brain edema model rats established by unilateral common
      carotid artery injection of Bacillus pertussis 250 million/kg; Group E: model
      rats administered by ANP 278 mg/kg 1 hr before modeling; Group F: model rats
      administered by drug II 222.7 mg 1 hr before modeling. Blood sample and brain
      tissue in Group D were obtained 4 hrs after modeling and those in other groups
      obtained 5 hrs after drug administration. The total activity of lactate
      dehydrogenase (LDH) in serum and brain tissue was determined by colorimetry and
      that of serum LDH isoenzymes (LDH(1-5)) were determined by gel electrophoresis.
      RESULTS: As compared with Group A, LDH, LDH1 and LDH2 activities increased in
      Group D (P < 0.01), and increased also in Group B and C (P < 0.05), while LDH4
      and LDH5 decreased obviously in Group B and C. But except that of LDH5, no
      significant difference of LDH(1-4) in brain tissue and serum was shown in
      comparison of Group B and C. As compared with Group D, LDH was lower (P < 0.01)
      and LDH5 was higher (P < 0.01) in Group E and F without significant difference,
      LDH2, LDH3 were lower in Group E (P < 0.01) but unchanged in Group F, LDH1 and
      LDH4 were not changed in Group E but significantly lowered in Group F (P < 0.05
      and P < 0.01). CONCLUSION: Administration of ANP in normal physiologic condition
      would cause damage on myocardium and kidney to certain extent, administration of
      ANP and drug II in pathologic (infectious brain edema) would suppress the hyper
      activated LDH, with no significant difference between the effects of drug II and
      ANP. However, CA and RA in ANP are proven to have influence on the serum LDH
      isoenzymes, indicating that the two ingredients may have some potential
      pharmacological effects.

PMID- 15957840
TI  - [Effect of sour TCM compound recipe on insulin resistance in experimental rats
      with diabetes mellitus type 2].
AB  - OBJECTIVE: To study the effect of sour TCM compound Recipe (SCCR) on insulin
      resistance in experimental rats with diabetes mellitus type 2 (DM2), under the
      guidance of TCM doctrine of "sour restrains sweet". METHODS: Model rats of DM2
      were established by 8 weeks' feeding with high calorie forage combined with
      intraperitoneal injection of small dose of streptozotocin, and treated with SCCR
      (15 g/kg of crude drug/day). Levels of fasting blood glucose (FBG), serum
      insulin, free fatty acids (FFA), tumor necrosis factor a (TNF-alpha), combining
      capacity and constant of insulin receptor in liver were determined before
      treatment and 4, 8 and 12 weeks after treatment, and the insulin sensitive index
      was calculated. The data were compared with those in the model group (untreated),
      sweet TCM compound recipe group and bitter TCM compound group (treated with sweet
      and bitter Chinese drugs respectively) and the control group (treated with
      dimethyldiguanide). RESULTS: SCCR could markedly reduce the FBG, serum FFA and
      TNF-alpha levels in rat model of DM2, stimulate the secretion of insulin, raise
      the combining capacity and constant of insulin receptor in liver and improve the
      insulin sensitivity, as compared with the effect of sweet or bitter Chinese
      compound recipe, the difference was significant (P < 0.05). CONCLUSION: SCCR
      could improve the glucose metabolic disorder and ameliorate the degree of insulin
      resistance in DM2 model rats, with the effect superior to those with sweet or
      bitter taste, which illustrates primarily that the therapeutic principle of "sour
      restrains sweet" of TCM is true of science in a certain degree and having its
      guiding significance in clinical practice.

PMID- 15957841
TI  - [Effect of rhodiola on expressions of Flt-1, KDR and Tie-2 in rats with ischemic
      myocardium].
AB  - OBJECTIVE: To investigate the effect of rhodiola on expression of vascular
      endothelial growth factors receptors (VEGFR) in myocardium of rats after
      myocardial infarction. METHODS: On the basis of successful establishment of
      myocardial infarction rat model, the experimental animals were divided into the
      model group, the rhodiola group, the positive control group and the sham-operated
      group, they were sacrificed after 6 weeks feeding. Their hearts were resected and
      embedded in paraffin to make sections with standard immunohistochemistry stain.
      Then the stained slices were analyzed in the IMS cell imagine analysis system
      using immunohistochemical quantitative analysis software. The field of vision of
      left ventricular myocardial tissue in three sites selected from the marginal area
      of infarction in each slice were determined, the mean value was then converted to
      positive area. Meanwhile, the mean optical density (OD) was calculated and the
      various expressions of VEGFR, i.e. Flt-1, KDR and angiopoietin receptor (Tie-2)
      were measured. RESULTS: The expressions of Flt-1 and Tie-2 in myocardial tissue
      were significantly increased in the rhodiola treated group after treatment,
      showing significant difference as compared with those in the positive control
      group and the model group (P < 0.05). The expression of KDR in myocardium after
      rhodiola intervention was higher than that in the sham-operated and nonintervened
      group (P < 0.05), but insignificantly different to that in the positive control
      group and model group. CONCLUSION: Rhodiola could improve angiogenesis to
      ameliorate myocardial ischemia by regulating the expression of Flt-1 and Tie-2 in
      ischemic myocardium.

PMID- 15957842
TI  - [Observation on clinical efficacy of combined therapy of zinc supplement and
      jinye baidu granule in treating human cytomegalovirus infection].
AB  - OBJECTIVE: To explore the clinical efficacy of the combined therapy of zinc
      supplement and Jinye Baidu granule (JBG) on human cytomegalovirus (HCMV)
      infection. METHODS: One hundred and forty patients with positive HCMV-IgM were
      randomly divided into four groups, with 35 cases in each group, that is, the
      control group (only medicated with JBG), the high-, moderate- and low-dose zinc
      combined groups (treated with JBG combined with zinc gluconate tablet at dose of
      30 mg, 20 mg, 10 mg every day respectively). The negative conversion rate of HCMV
      IgM was observed. RESULTS: Insignificant difference in the negative conversion
      rate was shown in comparison of the control group with the low dose group (P >
      0.05), and in comparison of the high dose with the moderate dose group (P >
      0.05); however, the rate was significantly lower in the control group than that
      in the moderate dose and high dose group (P < 0.05). CONCLUSION: Combined therapy
      of zinc supplement and JBG can significantly increase the negative conversion
      rate of HCMV-IgM. The optimal dosage of zinc gluconate tablet was 20 mg once a
      day.

PMID- 15957844
TI  - [Clinical research on relationship between angiogensis and TCM syndrome type of
      cyclomastopathy].
AB  - OBJECTIVE: To study the relationship between angiogensis and TCM Syndrome type of
      cyclomastopathy (CMP) to investigate the objective standardization of TCM
      Syndrome diagnosis of the disease. METHODS: One hundred and forty patients with
      CMP were divided into three groups according to TCM syndrome typing. The
      pathological type, grade and expressions of vascular endothelial growth factor
      (VEGF), basic fibroblast growth factor (bFGF) and microvascular density (MVD) in
      mammary biopsy were observed. RESULTS: The expressions of VEGF, bFGF and MVD was
      different in CMP patients of different TCM types and pathological grades (P <
      0.05). The proportion of atypical proliferation, the count of MVD and the
      expression of VEGF and bFGF were higher in patients of phlegm and stasis type
      than those in Gan stagnation caused Qistagnation type and Chong and Ren meridians
      disorder type. CONCLUSION: TCM Syndrome type of CMP patients is related with
      vascular activity and grade of angiogensis. The pathological characteristics of
      mammary tissue and expression of VEGF, bFGF and MVD can be regarded as the
      objective indexes of TCM typing and clinical efficacy evaluation for CMP.

PMID- 15957843
TI  - [Clinical observation on treatment of cancerous hydrothorax by aiyishu
      injection].
AB  - OBJECTIVE: To investigate the therapeutic effects of Aiyishu Injection (AYSI) on
      cancerous hydrothorax, quality of life (QOF), and cellular immune function of
      patients. METHODS: Sixty late-stage cancer patients accompanied hydrothorax were
      randomly divided into the experimental group (EG) and the control group (CG),
      with thirty patients in each group. After thoracenteses being carried out in all
      patients for draining off hydropsy, to the patients in EG, AYSI was medicated, 50
      ml by intrathoracic and another 50 ml by intravenous injection; while to the
      patients in CG chemotherapeutic agent or interleukin-2 (IL-2) was given. The same
      treatment, thoracentesis and medication, was repeated 3 days later. After 4
      weeks, the volume of pleural effusion was measured with B-mode ultrasound to
      evaluate the therapeutic effects of AYSI. QOF, body weight and T-lymphocyte
      subsets were compared between the two groups before and after treatment. RESULTS:
      The clinical efficacy was significantly higher in EG than that in CG (P < 0.01).
      Besides, QOF was significantly improved (P < 0.05) and levels of CD3+ , CD4+ ,
      CD4+ /CD8+ in peripheral blood increased in EG after treatment, which were
      significantly different to those in CG (P < 0.01, P < 0.05). CONCLUSION: AYSI has
      definite therapeutic effects on cancerous hydrothorax, it could improve QOF and
      cellular immune function in patients with cancer.

PMID- 15957845
TI  - [Postmenopausal osteoporosis and blood stasis].
AB  - OBJECTIVE: To investigate whether blood stasis is one of the main causes in the
      pathogenesis of postmenopausal osteoporosis. METHODS: The clinical manifestation
      of blood stasis syndrome were comprehensively scored in sixty postmenopausal
      osteoporosis patients, their vascular endothelial function and platelet
      activating capacity were also detected, and compared with those in 30 healthy
      women as control. RESULTS: The molecular indexes as vascular endothelial function
      and platelet activating capacity, as well as comprehensive scores of clinical
      manifestation of blood stasis syndrome in postmenopausal osteoporosis patients
      were significantly different to those of healthy women (P < 0.05, P < 0.01).
      CONCLUSION: There is objective molecular pathologic change of blood stasis
      syndrome in postmenopausal osteoporosis. Blood stasis plays an important role in
      pathogenesis of postmenopausal osteoporosis.

PMID- 15957846
TI  - [Exploration on central neurobiological mechanisms of Gan in taking charge of
      dispersion and regulating emotion].
AB  - Methods and thoughts of the further research on central neurobiological
      mechanisms of Gan in taking charge of dispersion and regulating emotion are
      discussed. By applying the holistic approach and homeostasis theory, combined
      with modern psychological stress theory, the authors put forward their hypothesis
      of study. They offered that the TCM theory of "Gan takes charge of dispersion and
      could regulate emotion" is affirmatively to have certain mechanisms of central
      neurobiology. So, cut-in from the point of psychological stress reaction,
      adopting the research thoughts of "prescription-syndrome-therapeutic
      effectiveness--essence of Zang-Fu function", a model of chronic psychological
      stress reaction (CPSR) for imitating the process of comprehensive pathologic
      change due to Gan fails to take charge of dispersion and leads to emotional
      disorder was established. It is considered based on analysis of materials
      obtained from previous studies, that the central neurobiologic mechanism of so
      called dispersion, which Gan in charge of, is related to the regulation of
      hypothalamus-pitutary-adrenal gland axis. Concretely, the function of Gan in TCM
      may be, in the gross, related with the changes of multiple neurotransmitters and
      their synthetase produced in the process of CPSR (emotional disorder) regulation,
      such as neuropeptides, hormones, cyclic necleotide system and Fos protein
      expression, showing the characteristics of multiple links, multiple levels and
      multiple targets, with the effects involve several brain regions including
      various clusters of nuclei in hypothalamus, hippocampus and amygdala, etc.

PMID- 15957847
TI  - [Preliminary discussion on cultural expression for English translation of TCM
      according to receptive theory].

PMID- 15957848
TI  - [Fever of unknown origin. Avoid a blind therapeutic intervention!].

PMID- 15957849
TI  - [Microbiological diagnosis in general practice. What must be considered in tissue
      sampling].

PMID- 15957851
TI  - [Injection treatment of patients with intervertebral disk displacement.
      (interview by Thomas Meissner)].

PMID- 15957852
TI  - [Dysmorphobia. When a "flaw" is removed, the next one reveals itself].

PMID- 15957853
TI  - [Quality management program for contract physicians. In an unbelievably short
      time a superior new concept is developed].

PMID- 15957854
TI  - [More and more abdominal operations can be performed with minimally invasive
      techniques].

PMID- 15957855
TI  - [Laparoscopic cholecystectomy is the current standard intervention].
AB  - In the case of gallstone disease a differentiation is made between uncomplicated
      symptomatic cholecystolithiasis and acute cholecystitis. In either condition,
      differentiation may be rendered more complicated by the simultaneous presence of
      choledocholithiasis. Today, the standard intervention for the removal of the
      gallbladder is the laparoscopic modality. Early laparoscopic cholecystectomy is
      now the regular approach, since the former practice (antibiotic therapy and
      surgery in the inflammation-free interval) led to a considerable delay, which was
      often accompanied by massive intra-abdominal adhesions and which resulted in an
      increase in the conversion rate.

PMID- 15957856
TI  - [Laparoscopic colon surgery].
AB  - Such a wealth of experience with the laparoscopic surgery has since been gained
      in specialized centers that laparoscopic colon surgery can now be recommended for
      the treatment of both benign and malignant diseases of the large bowel and
      rectum. Faster postoperative recovery, a shorter hospital stay and the presumably
      superior oncological results are not only patient-friendly, but also pass muster
      in terms of economics. In the future, there will be a greater concentration of
      such interventions in specialized centers, since only in such facilities can the
      required quality and further advances be expected.

PMID- 15957857
TI  - [Comparison of various methods of surgical hernia repair].
AB  - Over the last 15 years, a number of different procedures for hernia repair have
      been developed. Apart from the open techniques, with or without the use of a
      prosthetic mesh or mesh plug, endoscopic procedures such as transabdominal
      preperitoneal (TAPP), and totally endoscopic preperitoneal (TEPP), hernioplasty
      are now established operations. In the present paper, the common open surgical
      procedures are compared with the minimally invasive repairs with regard to
      practicability, postoperative wound pain and complications, mobilization,
      recurrence rates and cosmesis. In the view of the authors, the standard method
      for inguinal hernial repair is the open Lichtenstein procedure or the Rutkow
      patch and plug method.

PMID- 15957858
TI  - [Tumor markers--how they should be applied].
AB  - Determination of a tumor marker is currently not suitable method for screening
      purpose (exception: PSA and thyroglobulin). Tumor marker determination cannot be
      employed to exclude the presence of a tumor. Prior to surgery, however, such
      determination is desirable, and in the case of germ cell tumors even mandatory.
      Postoperatively, or after termination of adjuvant chemotherapy and/or
      radiotherapy, determination of tumor markers as an individual baseline is
      necessary for the further disease course. During the course of the disease and
      for follow-up care, the kinetic development of tumor factors is, in comparison
      with the individual baseline values, of decisive importance. However, in order to
      ensue correct interpretation it is important to use the same test system.

PMID- 15957859
TI  - [Medication, steel or radiation? The appropriate strategy to treat facial
      neuralgia].

PMID- 15957860
TI  - [EBM 2000 plus: KBV announces further changes].

PMID- 15957861
TI  - [The new EBM confuses family practitioners. No. 03120 not covered in chronic
      disease entities].

PMID- 15957862
TI  - [Federal judges sharpen responsibility for patient education].

PMID- 15957863
TI  - [Leaving Helicobacter pylori no chance. Triple therapy should consider resistance
      status].

PMID- 15957864
TI  - [Risk factor Helicobacter pylori. Prevention of stomach carcinoma].

PMID- 15957865
TI  - [Vertigo in young adults. The ground swings--anxiety spreads].

PMID- 15957866
TI  - ["Signs of survival"--a gallery association of HIV infected patients. It has
      become too quiet about AIDS].

PMID- 15957867
TI  - Africa faces apocalypse as AIDS and migration decimate key staff.

PMID- 15957868
TI  - How to stay on the right side of the infection control code.

PMID- 15957869
TI  - Quality in practice.
AB  - Under the new GP contract, nurses can have a significant role in ensuring quality
      of patient care and even become partners in their practices.

PMID- 15957870
TI  - First contact.
AB  - With more an more GPs opting not provide out-of-hours services, nurses are
      stepping into the breach to meet patients' needs. Telephone triage and emergency
      care centres are just two examples of the new service provision.

PMID- 15957871
TI  - Stand up to bullies.

PMID- 15957872
TI  - The value of clinical reflection following the death of a baby.

PMID- 15957873
TI  - Return trauma.

PMID- 15957874
TI  - The effects of dyslexia on the work of nurses and healthcare assistants.
AB  - AIM: To explore the effects of being dyslexic on the working lives of nurses and
      healthcare assistants (HCAs), and to identify what might be done to improve their
      working lives. METHOD: A qualitative approach was taken comprising semi
      structured interviews and interpretative data analysis. Seven nurses and HCAs
      took part in the study. FINDINGS: Dyslexia affects each individual differently
      and may affect career choice and career progression. Appropriate support from
      colleagues and employers is important. The participants identified dyslexia
      friendly practices and made suggestions for improvements. CONCLUSION: Nurses and
      HCAs with dyslexia can make a major contribution to patient care, although
      dyslexia can affect their work in many different ways. Establishing a dyslexia
      friendly workplace would help them to achieve their maximum potential.

PMID- 15957875
TI  - Reporting incidents of violence and aggression towards NHS staff.
AB  - Violence and aggression against nursing staff have been the subject of an ongoing
      campaign. However, incidents of violence continue to be under-reported. This
      article discusses factors leading to under-reporting of incidents and focuses on
      how nursing staffs' attitudes and responses to violence may contribute to the
      likelihood of reporting incidents. Change management techniques are proposed to
      address the under-reporting of incidents and to improve the work environment.

PMID- 15957876
TI  - Paracetamol poisoning: physiological aspects and management strategies.
AB  - This article identifies the physiological aspects of paracetamol poisoning, as
      well as appropriate treatments. Trends in paracetamol use and initiatives to
      reduce rates of self-harm are discussed, as well as clinical practice and ways to
      determine severity of poisoning.

PMID- 15957877
TI  - Administration of medicines.

PMID- 15957878
TI  - Skills for life.

PMID- 15957879
TI  - First-time nerves.

PMID- 15957880
TI  - Directed ortho metalation methodology. The N,N-dialkyl aryl O-sulfamate as a new
      directed metalation group and cross-coupling partner for Grignard reagents.
AB  - [reaction: see text] The ortho metalation (RLi/THF/-93 degrees C) of 3 followed
      by quench with a variety of electrophiles constitutes a new general route to
      substituted aryl O-sulfamates 4a-k. The Kumada-Corriu cross-coupling of O
      sulfamates 4e, 4n-s, and 6a with Grignard reagents gives biaryls 9a-m, and the
      use of 2-halo and boron derivatives 4h, 4i, and 4k for Suzuki-Miyaura cross
      coupling and generation of benzynes leads to naphthols 7a and 7b. A relative
      metalation ranking of the OSONEt(2) is reported.

PMID- 15957881
TI  - Directed ortho metalation-based methodology. Halo-, nitroso-, and boro-induced
      ipso-desilylation. Link to an in situ Suzuki reaction.
AB  - [reaction: see text] Treatment of DoM-derived silylated aromatics 2-4 under
      standard electrophilic halogenation conditions cleanly affords ipso-desilyation
      products 5-7, while nitration of methoxy-substituted analogues 8, 9 leads to non
      ipso isomers 10, 12 and 11, 13, controlled by a silicon steric effect. Sequential
      ipso-borodesilylation of 2a, 3a, and 20 followed by treatment with aryl halides
      under Pd-catalyzed conditions constitutes an in situ Suzuki-Miyaura cross
      coupling protocol to biaryls and heterobiaryls 23.

PMID- 15957882
TI  - Catalytic enantioselective synthesis of key intermediates for triazole antifungal
      agents.
AB  - [reaction: see text] A short-step synthesis of versatile chiral building blocks
      for triazole antifungal agents such as ZD0870 and Sch45450 was developed via
      catalytic enantioselective cyanosilylation of electron-deficient ketones as the
      key step. High enantioselectivity was produced using a catalyst prepared from
      Gd(HMDS)(3) and ligand 5 in a 2:3 ratio. This new catalyst preparation method was
      superior to the previous method using Gd(O(i)Pr)(3) as a metal source. A
      rationale for the difference is proposed on the basis of structural studies of
      the catalyst complexes using ESI-MS.

PMID- 15957883
TI  - Position of coordination of the lithium ion determines the regioselectivity of
      demethylations of 3,4-dimethoxymorphinans with L-selectride.
AB  - [reaction: see text] L-Selectride is an efficient agent for the 3-O-demethylation
      of opioids and is known to cleave the least hindered methoxyl group in a
      molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L
      Selectride gave selective 4-O-demethylation, rather than cleavage of the less
      hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave
      selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride
      mediated O-demethylation can be manipulated through altering the position of
      coordination of the lithium ion.

PMID- 15957884
TI  - Small-molecule diversity using a skeletal transformation strategy.
AB  - [reaction: see text] We describe a short synthetic sequence resulting in >4000
      skeletally diverse small molecules that have three distinct skeletal frameworks
      among other unique structural features. The sequence entails skeletal
      transformations pioneered by Winterfeldt and co-workers. We use epoxide ring
      openings and subsequent functionalizations that provide, e.g., spirocyclic
      oxazolidines, Lewis acid catalyzed Diels-Alder reactions of a steroid-derived
      diene that afford stable and isolable ring B adducts, and subsequent retro-Diels
      Alder fragmentations that yield 14-membered paracyclophanes.

PMID- 15957885
TI  - Catalytic enantioselective Diels-Alder reaction via a chiral indium(III) complex.
AB  - [reaction: see text] A chiral indium complex has been developed to effect high
      enantioselectivities in catalyzing enantioselective Diels-Alder reaction. The
      cycloaddition of a variety of cyclic and open-chained dienes to 2-methacrolein
      and 2-bromoacrolein resulted in good yields and excellent enantioselectivities
      (up to 98% ee).

PMID- 15957886
TI  - Preparation of polyfunctional arylmagnesium reagents bearing a triazene moiety. A
      new carbazole synthesis.
AB  - [reaction: see text] The reaction of iodo- or bromo-substituted aryltriazenes
      with i-PrMgCl.LiCl generates the corresponding magnesiated derivatives which
      react with various electrophiles (acid chlorides, 3-iodoenones, allylic halides,
      aldehydes) affording polyfunctional triazenes. They can be readily converted to
      the corresponding polyfunctional aryl iodides. This new synthetic strategy was
      applied to prepare functionalized carbazoles.

PMID- 15957887
TI  - Asymmetric synthesis of [7]helicene-like molecules.
AB  - [reaction: see text] A new approach to nonracemic [7]helicene-like molecules has
      been developed. Stereoselective Co(I)-mediated [2 + 2 + 2] cycloisomerization of
      aromatic triynes containing an asymmetric carbon atom produces [7]helicene-like
      scaffolds in diastereomeric ratios up to 100:0. This central-to-helical chirality
      transfer can be controlled by the absolute configuration at the asymmetric center
      and by the presence of carbon substituents.

PMID- 15957888
TI  - Model systems for flavoenzyme activity: site-isolated redox behavior in flavin
      functionalized random polystyrene copolymers.
AB  - [reaction: see text] A model system has been developed to study the redox
      behaviors of flavin derivatives appended onto random polystyrene copolymers
      through "click" chemistry strategies. The results demonstrate that flavin units
      attached onto polymers exhibit site-isolated redox behaviors, yielding new
      materials with electrochemically tunable associations (K(a)(ox) = 450 M(-)(1),
      K(a)(red) = 18,200 M(-)(1)) to complementary diamidopyridine (DAP) functionality.

PMID- 15957889
TI  - Highly diastereoselective Diels-Alder reactions of Baylis-Hillman adducts.
AB  - [reaction: see text] Baylis-Hillman adducts were found to be excellent
      dienophiles in Diels-Alder reactions, providing essentially complete
      diastereocontrol (although mixtures of endo/exo isomers) with all dienes.

PMID- 15957890
TI  - Self-assembling porphyrin-modified peptides.
AB  - [structure: see text] We report the synthesis and characterization of a novel
      supramolecular assembly that features long-range electronic coupling between
      porphyrins covalently attached to a designed peptide scaffold. The resulting
      construct self-assembles to form extended organized aggregates in which the
      porphyrins engage in exciton coupling.

PMID- 15957891
TI  - The [4 + 3]-cycloaddition/quasi-Favorskii process. Synthesis of the carbocyclic
      core of tricycloclavulone.
AB  - [reaction: see text] The [4 + 3]-cycloadduct derived from the reaction of 2,5
      dibromocyclopentanone with cyclopentadiene was converted via a quasi-Favorskii
      rearrangement and ring-opening, ring-closing metathesis sequence to the
      carbocyclic core of the prostanoid tricycloclavulone.

PMID- 15957892
TI  - Facile conversion of o-quinones into 1,3-dioxoles.
AB  - [reaction: see text] o-Quinones are transformed into the corresponding 1,3
      dioxoles in a single-step process by cathodic reduction in dichloromethane.

PMID- 15957893
TI  - Enantioselective rhodium enolate protonations. A new methodology for the
      synthesis of beta2-amino acids.
AB  - [reaction: see text] Rhodium-catalyzed conjugate addition of an aryl boronic acid
      to alpha-methylamino acrylates followed by enantioselective protonation of the
      oxa-pi-allylrhodium intermediate provides access to aryl-substituted beta(2)
      amino acids. The impact of the different variables of the reaction on the levels
      of enantioselectivity has been assessed.

PMID- 15957894
TI  - Palladium-catalyzed tandem N-arylation/carboamination reactions for the
      stereoselective synthesis of N-aryl-2-benzyl pyrrolidines.
AB  - [reaction: see text] The tandem N-arylation/carboamination of gamma-amino alkenes
      with two different aryl bromides provides rapid entry to differentially arylated
      N-aryl-2-benzyl pyrrolidine derivatives in good yields with good to excellent
      levels of diastereoselectivity. The selective diarylation is achieved in a one
      pot process by an in situ modification of the palladium catalyst via phosphine
      ligand exchange.

PMID- 15957895
TI  - Enantioselective epoxidation of alpha,beta-enones promoted by alpha,alpha
      diphenyl-L-prolinol as bifunctional organocatalyst.
AB  - [reaction: see text] An operationally simple and mild protocol for the catalytic
      enantioselective epoxidation of alpha,beta-unsaturated ketones has been
      estabilished using commercially available alpha,alpha-diphenyl-l-prolinol as
      bifunctional organocatalyst and tert-butyl hydroperoxide (TBHP) as oxidant. The
      epoxides have been obtained in good yields and with up to 80% ee.

PMID- 15957896
TI  - Chiral Bronsted acid catalyzed enantioselective hydrophosphonylation of imines:
      asymmetric synthesis of alpha-amino phosphonates.
AB  - [reaction: see text] A cyclic phosphoric acid derivative, derived from (R)-BINOL,
      was used as a chiral Bronsted acid (10 mol %) in hydrophosphonylation of
      aldimines with diisopropyl phosphite at room temperature. Alpha-amino
      phosphonates were obtained with good to high enantioselectivities.

PMID- 15957897
TI  - Total synthesis of hyacinthacine A1 and 3-epi-hyacinthacine A1.
AB  - [reaction: see text] Total synthesis of hyacinthacine A(1) and its epimer at C3
      is described. The synthesis includes a stereocontrolled carboazidation of a
      chiral allylsilane as a key step. C-Si bond oxidation and reduction of the azide,
      with ring-closure, complete the total synthesis, which establishes the absolute
      configuration of 3.

PMID- 15957898
TI  - Effective synthesis of 1beta-acyl glucuronides by selective acylation.
AB  - [reaction: see text] Acyl glucuronides are vital metabolites for many carboxylic
      acid containing drugs. We report an efficient new method for the chemical
      synthesis of these molecules by selective 1beta-acylation of allyl glucuronate
      with carboxylic acids catalyzed by HATU and then mild deprotection through
      treatment with Pd(PPh(3))(4) and morpholine. The method is effective for a range
      of aryl and alkyl carboxylic acids, including important drugs.

PMID- 15957899
TI  - Control of proton transfer: intramolecular vs intermolecular.
AB  - [reaction: see text] Proton transfer in ketonization of enolates is a critical
      step in a myriad of organic reactions. Its stereochemistry has been the object of
      our studies since we reported kinetic protonation from the less hindered face of
      the molecule under kinetic control some decades ago. Very recently, we have
      succeeded in reversing the stereochemistry using 2-pyridyl groups to deliver the
      proton. We now report intramolecular delivery by other moieties and control of
      intramolecular versus intermolecular proton delivery.

PMID- 15957900
TI  - Control of diastereoselectivity by solvent effects in the addition of Grignard
      reagents to enantiopure t-butylsulfinimine: syntheses of the stereoisomers of the
      hydroxyl derivatives of sibutramine.
AB  - [reaction: see text] An efficient method has been developed to prepare all four
      isomers of the hydroxyl derivatives of sibutramine by addition of Grignard
      reagents (R)- or (S)-5 to a single enantiomer of sulfinyl imine (R)-1 simply by
      tuning the reaction solvent. The phenomenon of the reversed diastereoselectivity
      in CH(2)Cl(2) and THF implied that the reaction may proceed through a chelated
      cyclic transition state in CH(2)Cl(2) and nonchelated acyclic transition state in
      THF.

PMID- 15957901
TI  - Metal-containing trifurcate receptor that recognizes and senses citrate in water.
AB  - [reaction: see text] The binding tendencies toward carboxylates of a trifurcated
      receptor containing three copper(II)-cyclam subunits have been investigated in
      pure water, through the displacement of a fluorescent indicator. The receptor is
      tailor-made for the recognition of tricarboxylates, e.g., citrate, whose three
      negatively charged oxygen atoms interact with the three coordinatively
      unsaturated Cu(II) centers.

PMID- 15957902
TI  - Visible colorimetric fluoride ion sensors.
AB  - [structure: see text] Five new urea derivative naphthalene compounds were
      synthesized by a reaction of 1,8-diaminonaphthalene and the corresponding
      isocyanates and showed a distinct color change only when treated with fluoride
      ions.

PMID- 15957903
TI  - A molecular switch with pH-controlled absolutely switchable dual-mode
      fluorescence.
AB  - [reaction: see text] A simple-structured molecule (L1) bearing anthracene
      fragments at both ends of diethylenetriamine chain behaves as a fluorescent
      molecular switch with pH-controlled absolutely switchable dual-mode fluorescence
      in water; each mode consists of monomer (pH <9) and excimer (pH >9) emissions.

PMID- 15957904
TI  - Dynamic combinatorial libraries of disulfide cages in water.
AB  - [structure: see text] Dynamic combinatorial libraries (DCLs) containing water
      soluble disulfide-linked cages (alongside macrocyclic structures) have been
      generated and characterized. Unlike most other strategies for generating
      molecular cages, the structures are held together by covalent bonds, which are
      formed under thermodynamic control. The diversity of the cages generated opens
      new possibilities for a generalized combinatorial strategy toward molecular
      encapsulation.

PMID- 15957906
TI  - The capture of sym-[8]annuldiyne: the cyclooctadienyne-eta2-ynyl potassium
      zwitterionic radical.
AB  - [reaction: see text] Reaction of 1,4-dibromo-[8]annulene (C(8)H(6)Br(2)) with
      potassium tert-butoxide in THF followed by exposure to potassium metal leads to
      the formation of the anion radical of sym-[8]annuldiyne. The rapid interchange of
      Jahn-Teller-induced alternating bond angle conformers of sym-[8]annuldiyne is
      halted by ion association with a metal-crown ether complex forming the
      cyclooctadienyne-eta(2)-ynyl potassium zwitterionic radical, rendering all four
      protons nonequivalent. Neutral sym-[8]annuldiyne can form the [2 + 2] polymer,
      which is not soluble in the THF solution.

PMID- 15957905
TI  - Peptide bond isosteres: ester or (E)-alkene in the backbone of the collagen
      triple helix.
AB  - [structure: see text] Collagen is the most abundant protein in animals.
      Interstrand N-H...O=C hydrogen bonds between backbone amide groups form a ladder
      in the middle of the collagen triple helix. Isosteric replacement of the hydrogen
      bond-donating amide with an ester or (E)-alkene markedly decreases the
      conformational stability of the triple helix. Thus, this recurring hydrogen bond
      is critical to the structural integrity of collagen. In this context, an ester
      isostere confers more stability than does an (E)-alkene.

PMID- 15957907
TI  - Synthesis of aza-, oxa-, and thiabicyclo[3.1.0]hexane heterocycles from a common
      synthetic intermediate.
AB  - [reaction: see text] An efficient and stereospecific approach to the synthesis of
      structurally constrained aza-, oxa-, and thiabicyclo[3.1.0]hexane heterocycles
      has been achieved through application of the intramolecular cyclopropanation
      reaction of diazoacetates. The various constrained heterocycles (X = N, O, or S)
      are conveniently prepared from a common diol intermediate accessible from readily
      available cinnamyl alcohols. Application of the methodology to the synthesis of
      conformationally constrained oxazolidinone antibacterials is also discussed.

PMID- 15957908
TI  - Photolytic release of carboxylic acids using linked donor-acceptor molecules:
      direct versus mediated photoinduced electron transfer to N-alkyl-4-picolinium
      esters.
AB  - [reaction: see text] Efficient photorelease (Phi = 0.7) of carboxylic acids is
      achieved with a covalently linked mediator (benzophenone) protecting group (N
      alkyl-4-picolinium ester) molecule. The mechanism involves initial photoreduction
      of the mediator, followed by rapid electron transfer to the protecting group.

PMID- 15957909
TI  - Platinum-catalyzed intermolecular hydroamination of vinyl arenes with
      carboxamides.
AB  - [reaction: see text] Reaction of benzamide with 4-methylstyrene catalyzed by a
      1:2 mixture of [PtCl(2)(H(2)C=CH(2))](2) and P(4-C(6)H(4)CF(3))(3) (5 mol %) in
      mesitylene at 140 degrees C for 24 h led to the isolation of N-(1-p
      tolylethyl)benzamide in 85% yield. Electron-rich, electron-poor, and hindered
      vinyl arenes underwent Markovnikov hydroamination with a range of carboxamides
      and amide derivatives in moderate to good yield with excellent regioselectivity.

PMID- 15957910
TI  - Palladium-catalyzed cyanoesterification of norbornenes with cyanoformates via the
      NC-Pd-COOR (R = Me and Et) intermediate.
AB  - [reaction: see text] Palladium-catalyzed cyanoesterification of norbornenes
      proceeds stereoselectively via NC-Pd-COOR (R = Me and Et) complexes as
      intermediates.

PMID- 15957911
TI  - Straightforward approach to iminoxazines and azetidinimines via 1,4-additions of
      chelated enolates toward nitroalkenes.
AB  - [reaction: see text] Chelated amino acid ester enolates undergo 1,4-addition
      toward nitroalkenes in a highly stereoselective fashion. Trapping the nitronates
      formed in the addition step with chloroformates or acyl chlorides gives rise to
      highly reactive intermediates that directly undergo cyclization. Depending on the
      N-protecting group (PG) used, iminoxazines or azetidinimines are formed in a
      simple one-pot protocol.

PMID- 15957912
TI  - Fmoc solid-phase synthesis of peptide thioesters using an intramolecularn,S-acyl
      shift.
AB  - [reaction: see text] We describe the Fmoc solid-phase synthesis of peptide
      thioesters based on the alkylation of the safety-catch sulfonamide linker with a
      protected 2-mercaptoethanol derivative. The thioester is generated on the solid
      phase after the peptide chain assembly as a consequence of an intramolecular N,S
      acyl shift. Depending on the stability of the spacer separating the sulfonamide
      linker from the resin toward TFA, treatment of the peptidyl resin with TFA led to
      a soluble or supported deprotected thioester.

PMID- 15957913
TI  - Catalytic asymmetric diazoacetate cyclopropanation of 1-tosyl-3-vinylindoles. A
      route to conformationally restricted homotryptamines.
AB  - [reaction: see text] Substituted 1-tosyl-3-vinylindoles undergo catalytic
      asymmetric cyclopropanation with ethyl- and tert-butyldiazoacetate to afford N
      protected trans-2-(indol-3-yl)-1-cyclopropanecarboxylic esters in good yield and
      high enantiomeric excess (81-88% ee). The resulting cycloadducts are demonstrated
      to be useful intermediates for the synthesis of conformationally restricted,
      homotryptamine-like analogues such as BMS-505130.

PMID- 15957914
TI  - Versatile and stereoselective syntheses of orthogonally protected beta
      methylcysteine and beta-methyllanthionine.
AB  - [reaction: see text] Lantibiotics are a class of lanthionine (and/or beta
      methyllanthionine)-containing peptides with antibioitic activity against Gram
      positive bacteria. As part of our research effort directed toward the synthesis
      and mechanistic study of the lantibiotic peptide mersacidin (1), we report
      stereoselective syntheses of orthogonally protected beta-methylcysteine (beta
      MeCys) and beta-methyllanthionine (beta-MeLan), two key nonnatural amino acid
      components of the mersacidin architecture.

PMID- 15957915
TI  - Synthesis of the ABC fragment of the pectenotoxins.
AB  - [reaction: see text] A highly stereocontrolled synthesis of the C1-C16 ABC
      spiroacetal-containing fragment 5 of PTX7 (4) has been achieved. Appendage of the
      C ring to the AB fragment involved Wittig reaction of spiroacetal aldehyde 8 with
      a stabilized ylide 9 followed by displacement of allylic iodide 27 with a lithium
      acetylide to afford enyne 7. Fructose-derived chiral dioxirane and
      dihydroxylation were then used to introduce the correct functionality in the
      tetrahydrofuran C ring.

PMID- 15957916
TI  - Synthesis of a laterally branched polyamine from alpha-methylene-gamma
      butyrolactone.
AB  - [reaction: see text] A polyamine derivative was prepared from alpha-methylene
      gamma-butyrolactone. This method used Michael addition and lactone aminolysis
      followed by the nucleophilic substitution of the hydroxyl group by an azido
      group. The coupling of a lipophilic alkyne led to a polyamine that will be probed
      as a gene transfer agent.

PMID- 15957917
TI  - Cu(OAc)2-catalyzed N-arylations of sulfoximines with aryl boronic acids.
AB  - [reaction: see text] A simple and mild copper salt-catalyzed N-arylation of
      sulfoximines in high yields is reported. Cu(OAc)(2) activates aryl boronic acids
      for the reaction with NH-sulfoximines without additional base or heating.
      Furthermore, this new method allows the preparation of N-arylated sulfoximines,
      which have previously been more difficult to access.

PMID- 15957918
TI  - Practical synthesis of (Z)-polyaromatic and heteroaromatic vinylacetylenes.
AB  - [reaction: seet text] Two synthetic routes to several (Z)-polyaromatic and
      heteroaromatic substituted vinylacetylenes are described. The nature of aryl- or
      heteroaryl-substituted carboxaldehyde used as starting material dictated the
      choice of Wittig salt employed. A very attractive way to construct polyaromatic
      and pyridine-containing enynes is the reaction of polyaromatic and pyridine
      containing aldehydes with bromomethyltriphenylphosphonium bromide in the presence
      of potassium tert-butoxide followed by a Sonogashira desilylation procedure
      (method B).

PMID- 15957919
TI  - A silver-catalyzed domino route toward 1,2-dihydroquinoline derivatives from
      simple anilines and alkynes.
AB  - [reaction: see text] A silver-catalyzed domino reaction of simple anilines and
      alkynes generates 1,2-dihydroquinoline derivatives efficiently.

PMID- 15957920
TI  - Allylic etherification via Ir(I)/Zn(II) bimetallic catalysis.
AB  - [reaction: see text] An efficient allylic etherification of aliphatic alcohols
      with allylic carbonates has been achieved by an iridium catalysis using
      stoichiometric zinc alkoxides or a two-component bimetallic catalytic system
      where the Ir(I) catalyst acts on allylic carbonates to generate electrophiles
      while aliphatic alcohols are separately activated by Zn(II) coordination to
      function as nucleophilies. This reaction occurs with complete regiospecificity
      and tolerates a wide range of functional groups.

PMID- 15957921
TI  - Stereoselective synthesis of the tetrahydropyran core of polycarvernoside A.
AB  - [reaction: see text] A concise and stereoselective synthesis of the
      tetrasubstituted tetrahydropyran core of polycavernoside A was achieved in 55%
      overall yield from 3-benzyloxypropanal. A stereoselective allyl transfer reaction
      was used in the synthesis of enol ether 18 followed by a TFA-mediated cyclization
      to create the three new asymmetric centers in the tetrahydropyran with complete
      stereocontrol in a single-pot process.

PMID- 15957922
TI  - Novel oxa-di-pi-methane and Norrish type I reactions in the S2 (pi,pi*) excited
      state of a series of beta,gamma-unsaturated ketones.
AB  - [reaction: see text] Beta,gamma-unsaturated methyl ketones with electron
      withdrawing groups at the gamma-position of the ene moiety undergo ODPM
      rearrangements and Norrish type I reactions on direct irradiation at 254 nm. The
      results are consistent with the involvement of alkene S(2) (pi,pi*) as reactive
      excited states in these processes.

PMID- 15957923
TI  - Novel synthesis of castanospermine and 1-epicastanospermine.
AB  - [reaction: see text] Polyhydroxylated indolizidines have potential for treatment
      of HIV, hepatitis C and HSV infection, multiple sclerosis, angiogenesis, cancer,
      and diabetes. A new synthetic approach to the title compounds from a 5-C
      methoxypyranosyl azide has been developed. The route incorporates the aldol
      reaction and a novel catalytic reductive amination cascade to generate the
      indolizidine ring.

PMID- 15957924
TI  - Highly efficient solid-phase oxidative cleavage of olefins by OsO4-NalO4 in the
      intramolecular N-acyliminium Pictet-Spengler reaction.
AB  - [reaction: see text] In the present investigation, solid-supported peptide
      olefins were converted quantitatively to aldehydes via the OsO(4)-NaIO(4)
      mediated oxidative cleavage reaction. Addition of DABCO was essential to
      efficiently suppress the formation of hydroxymethyl ketone side products. The
      generated aldehydes were used in intramolecular N-acyliminium Pictet-Spengler
      reactions to produce highly pure pyrroloisoquinoline derivatives. The methodology
      was extended to allylglycine derivatives to enable the incorporation of
      pyrroloisoquinoline scaffolds within peptides.

PMID- 15957925
TI  - New synthetic route for the enantioselective total synthesis of salinosporamide A
      and biologically active analogues.
AB  - [reaction: see text] A total synthesis of the salinosporamide analogue 3 is
      described that starts with the novel cyclization 4 --> 5.

PMID- 15957926
TI  - Simple enantiospecific syntheses of the C(2)-diastereomers of omuralide and 3
      methylomuralide.
AB  - [reaction: see text] Syntheses of two novel omuralide derivatives are described.

PMID- 15957927
TI  - Novel PdII-mediated cascade carboxylative annulation to construct benzo[b]furan-3
      carboxylic acids.
AB  - [reaction: see text] Benzo[b]furan-3-carboxylic acid (2) was generated from 1 by
      forming three new bonds in one step via a Pd(II)-mediated cascade carboxylative
      annulation. The proposed mechanism was supported by the observation of an unusual
      acetylation of 1 as a side reaction together with an (18)O-labeling study.

PMID- 15957930
TI  - Solid-phase synthesis of diaryl sulfides: direct coupling of solid-supported aryl
      halides with thiols using an insoluble polymer-supported reagent.
AB  - [reaction: see text] Diaryl sulfides have been prepared by direct nickel(II)
      catalyzed coupling of thiols with iodoaryl bound to SynPhase polystyrene lanterns
      in the presence of polymer-supported borohydride.

PMID- 15957928
TI  - Practical and highly enantioselective synthesis of beta-alkynyl-beta-amino esters
      through Ag-catalyzed asymmetric mannich reactions of silylketene acetals and
      alkynyl imines.
AB  - [reaction: see text] A readily available iso-leucine-based phosphine ligand is
      used to promote Ag-catalyzed Mannich reactions between silylketene acetals and
      various alkynyl imines. Reactions can be effected in the presence of 5 mol %
      catalyst, without the need for rigorous exclusion of air, and with commercially
      available solvents (without purification) to afford the desired beta-alkynyl-beta
      amino esters in 84-94% ee and 61-91% isolated yield.

PMID- 15957929
TI  - Syntheses of ficuseptine, juliprosine, and juliprosopine by biomimetic
      intramolecular Chichibabin pyridine syntheses.
AB  - [structure: see text] Biomimetic intramolecular Chichibabin pyridine syntheses
      using two molecules of an aldehyde and 4-aminobutanal dimethyl acetal (6) proceed
      efficiently in AcOH at 95 degrees C to give 2,3-dihydro-1H-indolizinium salts.
      Reaction occurs at 25 degrees C if 1-pyrroline (5) is used instead of 6. This
      reaction has been used for a one-step synthesis of ficuseptine (1) and the first
      syntheses of juliprosine (2) and juliprosopine (17t), which is now assigned as
      the trans stereoisomer.

PMID- 15957931
TI  - Microwave-enhanced synthesis of N-shifted buflavine analogues via a Suzuki-ring
      closing metathesis protocol.
AB  - [reaction: see text] A novel, microwave-enhanced six-step synthesis was devised
      for the synthesis of N-shifted buflavine analogues. Microwave-enhanced Suzuki
      Miyaura cross-coupling and ring-closing metathesis reactions were used as the key
      steps. Microwave irradiation was found to enhance the ring-closing metathesis
      reaction to generate the otherwise difficultly obtainable medium-sized ring
      system of the target molecules.

PMID- 15957932
TI  - A simple construction of a bile acid based dendritic light harvesting system.
AB  - [structure: see text] A facile synthesis of a cholic acid derived dendritic
      structure labeled with nine naproxens and a single anthracene is reported. This
      multichromophoric, novel dendritic construct acts as an efficient molecular light
      harvester.

PMID- 15957933
TI  - Sporolides A and B: structurally unprecedented halogenated macrolides from the
      marine actinomycete Salinispora tropica.
AB  - [structure: see text] Analysis of the fermentation broth of a strain of the
      marine actinomycete Salinispora tropica has led to the isolation of two
      unprecedented macrolides, sporolides A (1) and B (2). The structures and absolute
      stereochemistries of both metabolites were elucidated using a combination of NMR
      spectroscopy and X-ray crystallography.

PMID- 15957935
TI  - Evidence for a transition state model compound of in-plane vinylic SN2 reaction.
AB  - [reaction: see text] To isolate a transition state model compound of an in-plane
      vinylic S(N)2 reaction, vinyl bromide 6 bearing a newly synthesized tridentate
      ligand derived from 1,8-dimethoxythioxanthen-9-one (5) was prepared as a
      precursor. Although irradiation of 6 gave demethylated benzofuran 12, a transient
      broad peak which indicates formation of the desired transition state model
      compound was observed in the laser flash photolytic study.

PMID- 15957934
TI  - Model studies of the histidine-tyrosine cross-link in cytochrome C oxidase reveal
      the flexible substituent effect of the imidazole moiety.
AB  - [reaction: see text] Experimental and theoretical studies were carried out to
      interrogate the effect of an imidazole substituent in each of the ortho, meta,
      and para positions on the pK(a), E degrees , and O-H BDE of phenol. The results
      reveal that imidazole substitution lowers the pK(a) of phenol and increases the E
      degrees of phenoxide due to its sigma-electron withdrawing ability (sigma(p)(-) =
      +0.21, sigma(m)(-) = +0.45) but decreases the O-H BDE and E degrees of phenol due
      to its pi-electron-donating ability (sigma(p)(+) = -0.45).

PMID- 15957936
TI  - Catalytic enantioselective allylation of ketones via a chiral indium(III)
      complex.
AB  - [reaction: see text] A chiral indium complex has been discovered to effect high
      enantioselectivities in the addition of allyltributylstannanes to ketones. The
      allylation of a variety of aromatic, alpha,beta-unsaturated and aliphatic ketones
      resulted in good yields and high enantioselectivities (up to 92% ee).

PMID- 15957937
TI  - Stereoselective synthesis of 2,6-disubstituted 3-piperidinols: application to the
      expedient synthesis of (+)-julifloridine.
AB  - [reaction: see text] The asymmetric synthesis of 2,6-disubstituted 3-piperidinols
      having a 2,3-cis and 2,6-trans relative stereochemistry was accomplished in three
      steps using the following sequence: stereocontrolled nucleophilic addition of an
      organomagnesium reagent to a chiral pyridinium salt; monohydrogenation of the
      resulting 2-substituted 1,2-dihydropyridine; and a one-pot, highly
      diastereoselective epoxidation-nucleophilic addition with a heteroatom
      nucleophile or an organometallic reagent. This methodology was applied to the
      expedient asymmetric synthesis of (+)-julifloridine in four steps.

PMID- 15957938
TI  - Convergent synthesis of a complex oxime library using chemical domain shuffling.
AB  - [reaction: see text] The synthesis of a complex hybrid oxime library is reported
      utilizing convergent ligation of alkoxyamine and carbonyl monomers via "chemical
      domain shuffling". Initial biological screening of the library against human
      small cell lung carcinoma (A549) cells led to the identification of a novel
      hybrid dimer in contrast to the corresponding monomeric compounds which were
      found to be inactive.

PMID- 15957940
TI  - Approaches to syn-7-substituted 2-azanorbornanes as potential nicotinic agonists;
      synthesis of syn- and anti-isoepibatidine.
AB  - [reaction: see text] Coupling of N-Boc-7-bromo-2-azabicyclo[2.2.1]heptane with
      aryl and pyridyl boronic acids incorporates aryl and heterocyclic substituents at
      the 7-position and leads to a preference for syn over anti stereoisomers.
      Incorporation of a chloropyridyl group followed by N-deprotection gives syn
      isoepibatidine. Facial selectivity in attack on 7-keto-2-azanorbornanes depends
      heavily on the N-protecting group leading to the first syn-7-hydroxy-2
      azabicyclo[2.2.1]heptane derivative.

PMID- 15957939
TI  - Stereoselective conjugate radical additions: application of a fluorous
      oxazolidinone chiral auxiliary for efficient tin removal.
AB  - [reaction: see text] A series of asymmetric free-radical-mediated intermolecular
      conjugate additions using a fluorous oxazolidinone chiral auxiliary has been
      completed. The fluorous auxiliary facilitated product isolation using fluorous
      solid phase extractions (FSPE), effectively removing excess organic and
      organometallic reagents. Parallel reactions carried out with a similar but
      nonfluorous norephedrine-derived oxazolidinone demonstrated the superior
      stereoselectivity and purification obtainable with the fluorous chiral auxiliary.

PMID- 15957941
TI  - Biosynthetic origins of C-P bond containing tripeptide K-26.
AB  - [reaction: see text] Primary metabolic precursors for K-26, a naturally occurring
      tripeptide phosphonic acid from Actinomyces sp. K-26, are investigated by heavy
      atom isotope labeled substrate incorporation experiments. A highly sensitive
      selected reaction monitoring (SRM)-based method for isotopic incorporation
      estimation in natural products is reported. The incorporation of heavy-atom
      isotope labeled tyrosine compounds into the (R)-1-amino-2-(4-hydroxyphenyl)
      ethylphosphonic acid moiety of compound K-26 suggests a new mechanism of
      biosynthesis of phosphonate functionality in natural products.

PMID- 15957942
TI  - Catalytic enantioselective indium-mediated allylation of hydrazones.
AB  - [reaction: see text] A facile and highly selective indium-mediated allylation of
      hydrazones utilizing BINOL ligands is described. Chiral (R)-3,3'
      bistrifluoromethylBINOL afforded homoallylic amines in up to 97% ee with
      stoichiometric ligand. Employing only 10 mol % ligand afforded selectivity of up
      to 92% ee.

PMID- 15957943
TI  - Alpha-hydroxy cyclopentenones from alpha-diketones.
AB  - [reaction: see text] Metalloenolates derived from alpha,beta-unsaturated alpha
      diketones undergo cyclization to alpha-hydroxy cyclopentenones. This is
      apparently the first reported Nazarov reaction that takes place in the presence
      of base.

PMID- 15957944
TI  - Total synthesis of cyclic tetrapeptide FR235222, a potent immunosuppressant that
      inhibits mammalian histone deacetylases.
AB  - [structure: see text] The total synthesis of FR235222, a potent immunosuppressant
      with in vivo activities, has been achieved. The key steps include assembling its
      (2S,9R)-2-amino-9-hydroxy-8-oxodecanoic acid residue via an olefin cross
      metathesis of a methyl (R)-lactate-derived homoallyl ketone with protected allyl
      amino acid and constructing its trans-(2R,4S)-4-methylproline unit from protected
      (R)-pyroglutamic acid in seven steps.

PMID- 15957945
TI  - Synthesis of pyragonicin.
AB  - [structure: see text] A stereocontrolled convergent synthesis of the annonaceous
      acetogenin pyragonicin (1) is presented. The key intermediates were accessed
      using asymmetric Horner-Wadsworth-Emmons (HWE) methodology. A reagent controlled
      zinc-mediated stereoselective coupling, joining the two highly functionalized
      intermediates 3 and 4, then provided the core structure.

PMID- 15957946
TI  - Total synthesis of the proposed structure for pyragonicin.
AB  - [structure: see text] The total synthesis of acetogenin 1 reported for
      pyragonicin and its 10-epimer 32 is described. The common THP ring system was
      stereoselectively constructed through a SmI(2)-induced reductive cyclization of
      beta-alkoxy acrylate 5 followed by Mitsunobu inversion, and each chiral center at
      C-10 was created by Brown's asymmetric allylation. Compound 1 had spectroscopic
      data consistent with that of natural pyragonicin, but a different optical
      rotation.

PMID- 15957947
TI  - Efficient aziridination of olefins catalyzed by mixed-valent dirhodium(II,III)
      caprolactamate.
AB  - [reaction: see text] A mild, efficient, and selective aziridination of olefins
      catalyzed by dirhodium(II) caprolactamate [Rh(2)(cap)(4).2CH(3)CN] is described.
      Use of p-toluenesulfonamide (TsNH(2)), N-bromosuccinimide (NBS), and potassium
      carbonate readily affords aziridines in isolated yields of up to 95% under
      extremely mild conditions with as little as 0.01 mol % Rh(2)(cap)(4). Aziridine
      formation occurs through Rh(2)(5+)-catalyzed aminobromination and subsequent base
      induced ring closure. An X-ray crystal structure of a Rh(2)(5+) halide complex,
      formed from the reaction between Rh(2)(cap)(4) and N-chlorosuccinimide, has been
      obtained.

PMID- 15957948
TI  - A concise synthesis of (+)-SCH 351448.
AB  - [structure: see text] We describe a highly convergent synthetic approach to the
      natural product (+)-SCH 351448 (1)-a hexane-soluble heptacoordinate monosodium
      salt of a C(2)-symmetrical macrocyclic dilactone. Our approach implements a
      photochemical acylation as the key step to combine two nearly identical but
      orthogonal C1-C29 fragments, followed by a base-induced intramolecular acylation
      and deprotection to yield the natural product.

PMID- 15957949
TI  - Asymmetric construction of quaternary carbon stereocenters: high stereoselection
      in Mukaiyama aldol reactions of 2-siloxyindoles with chiral aldehydes.
AB  - [reaction: see text] A new synthesis of enantiopure 3,3-disubstituted oxindoles
      by stereoselective Mukaiyama aldol reaction of 3-substituted 2-siloxyindoles and
      chiral, enantiopure aldehydes having nitrogen or oxygen substituents at the alpha
      carbon is described. When the C3 substituent of the prochiral nucleophile is aryl
      or heteroaryl, stereoselectivity is high (10-80:1).

PMID- 15957950
TI  - Stereoselective Nazarov cyclizations of bridged bicyclic dienones.
AB  - [reaction: see text] Bridged bicyclic dienones underwent silyl-directed Nazarov
      cyclization with generally very high diastereoselectivity. In most cases, a
      strong preference for cyclization to the product with an exo-disposed
      cyclopentenone was seen. However, the presence of additional unsaturation in the
      three-carbon bridge of a bicyclo[3.2.1]octadiene system caused complete reversal
      in selectivity with exclusive formation of the endo-cyclopentenone. The observed
      selectivities are believed to result from a combination of steric and electronic
      effects.

PMID- 15957952
TI  - The Rural Physician Associate Program: successful outcomes in primary care and
      rural practice.
AB  - The Rural Physician Associate Program (RPAP) has trained 1063 medical students in
      rural communities for the past 34 years and produced 658 primary care physicians
      and 521 physicians who currently practice in rural communities. While the
      students' experience in this nine-month clerkship is primarily clinic-based, they
      see patients in the emergency room, assist in surgery, deliver babies, attend
      physician meetings and participate in community health education. They experience
      real continuity of care by following a patient from the clinic or emergency room
      to the operating room and throughout their recovery. They diagnose a pregnancy,
      deliver the baby and then do the well-child examination in the clinic. The
      students recognize the value of this experience, as expressed in their final
      essays. They value the mentoring of the physicians, the relationship with the
      patients and the experiences in health care in which they play integral part.
      While the trend toward primary care in medical education is decreasing, the
      outcome of the RPAP program is holding steady at approximately 80%. Selection is
      certainly a factor, because many of the students who apply for RPAP have already
      expressed an interest in primary care. Additionally, the mentoring relationship
      with their preceptor, professionally and personally, and the ability to observe
      the lives of other practising physicians provides a reality check that may guide
      decisions. The enthusiasm for teaching, and the significant engagement with and
      impact on the community of the physicians may be another factor in deciding on
      primary care. Practising alongside physicians who find intellectual challenge and
      rewarding relationships in primary care is essential in continuing to produce
      primary care physicians of future.

PMID- 15957954
TI  - Treatment of experimental septic shock with microencapsulated antisense oligomers
      to NF-kappaB.
AB  - NF-kappaB is an ideal target for inhibition of proinflammatory cytokines. The
      purpose of this study was to determine if microencapsulated antisense oligomer to
      NF-kappaB can inhibit proinflammatory cytokine release in response to Escherichia
      coli endotoxin and bacteria. Microencapsulation takes advantage of the phagocytic
      function of the macrophage to deliver the oligomer intracellularly and enhance
      the effect. Albumin microcapsules 1 microm in size were prepared by a
      nebulization method containing antisense oligomers to NF-kappaB. E. coli
      endotoxin was incubated in 1 ml aliquots of whole blood. Microencapsulated
      antisense to NF-kappaB was given, and the inhibition of tumor necrosis factor
      (TNF), interleukin-1 (IL-1), IL-6, and IL-8 was compared with similar amounts of
      oligomer in solution. Endotoxic shock was produced in rats using E. coli
      endotoxin (15 mg/kg). Peritonitis was induced by injecting 10(10) CFU E. coli.
      Cytokines were measured after simultaneous and delayed (4 h) administration of
      antisense to NF-kappaB in microcapsules and solution form. TNF was suppressed by
      81% in whole blood, 56% in the endotoxic shock model, 89% in the peritonitis
      model (simultaneous treatment), and 56% in the delayed treatment group. Survival
      was 70% in the endotoxic shock group, 80% in the simultaneous peritonitis group,
      and 70% in the delayed treatment group. Microcapsule treatment using antisense to
      NF-kappaB suppressed TNF and IL-1 levels and mortality significantly better than
      all solution treatment groups in the whole blood model, endotoxic shock model,
      and peritonitis model.

PMID- 15957953
TI  - Review: hypoxia-inducible factor-1 (HIF-1): a novel transcription factor in
      immune reactions.
AB  - Hypoxia-inducible factor-1 (HIF-1) is a dimeric transcriptional complex that has
      been recognized primarily for its role in the maintenance of oxygen and energy
      homoeostasis. The HIF-1alpha subunit is O(2) labile and is degraded by the
      proteasome following prolyl-hydroxylation and ubiquitination in normoxic cells.
      The present review summarizes evidence that HIF-1 is also involved in immune
      reactions. Immunomodulatory peptides, including interleukin-1 (IL-1) and tumor
      necrosis factor-alpha (TNF-alpha), stimulate HIF-1 dependent gene expression even
      in normoxic cells. Both the hypoxic and the cytokine-induced activation of HIF-1
      involve the phosphatidylinositol- 3-kinase (PI3K) and the mitogen-activated
      protein kinase (MAPK) signaling pathways. In addition, heat shock proteins (HSP)
      and other cofactors interact with HIF-1 subunits. HIF-1 increases the
      transcription of several genes for proteins that promote blood flow and
      inflammation, including vascular endothelial growth factor (VEGF), heme oxygenase
      1, endothelial and inducible nitric oxide synthase (NOS) and cyclooxygenase-2
      (COX-2). The pharmacologic activation of the HIF-1 complex can be desirable in
      ischemic and inflammatory disorders. In contrast, HIF-1 blockade may be
      beneficial to prevent tumor angiogenesis and tumor growth.

PMID- 15957955
TI  - Novel interaction between nuclear coactivator CBP and the protein inhibitor of
      activated Stat1 (PIAS1).
AB  - cAMP response element binding protein (CREB)-binding protein (CBP) is a
      multifunctional transcriptional coactivator that plays important roles in gene
      regulation. CBP is expressed in murine embryonic orofacial tissue, where it is
      developmentally regulated. To identify nuclear factors associated with CBP in
      developing orofacial tissue, a yeast two-hybrid screen of a cDNA library derived
      from embryonic orofacial tissue from gestational days 11-13 mouse embryos was
      conducted. Using the carboxy terminal region of CBP as bait, the protein
      inhibitor of activated Stat1 (PIAS1) was identified as a novel CBP binding
      protein. The association of PIAS1 with CBP was confirmed in vitro by glutathione
      S-transferase (GST) pull-down assays and in vivo by coimmunoprecipitation.
      Reporter assays demonstrated that PIAS1 inhibited CBP-mediated transcriptional
      activation in the presence or absence of transforming growth factor-beta (TGF
      beta). These results identify PIAS1 as a novel binding partner for CBP and
      inhibitor of CBP-mediated transcription, suggesting that PIAS1 might play a role
      in regulating cell proliferation, migration, and differentiation during embryonic
      development.

PMID- 15957956
TI  - IFN-gamma: a cytokine essential for rejection of CTL-resistant, virus-infected
      cells.
AB  - We recently demonstrated differential susceptibility of cells expressing viral
      antigen to killing by antigen-specific cytotoxic T lymphocytes (CTLs). In
      addition, interferon-gamma (IFN-gamma) has been implicated in the clearance of
      some viruses from tissues. We explored the role of IFN-gamma in the cytotoxicity
      of Sendai virus-specific CTLs against virus-infected RL(male symbol)1 (T cell
      leukemia) or Meth A (fibrosarcoma) cells, as well as the growth of subcutaneously
      (s.c.) transplanted, virus-infected cells in IFN-gamma(+/+) or IFN-gamma(/) mice
      of the syngeneic strain (BALB/c). Sendai virus-specific CTLs were cytotoxic
      against virus-infected RL(male symbol)1 cells, and s.c. transplanted, virus
      infected RL(male symbol)1 cells were acutely rejected from IFN-gamma(+/+) or IFN
      gamma(/) mice. In contrast, the CTLs were inactive toward virus-infected Meth A
      cells, but s.c. transplanted, virus-infected Meth A cells were acutely rejected
      from IFN-gamma(+/+) but not IFN-gamma(/) mice. The s.c. growth of virus-infected
      Meth A cells in the mutant mice was markedly inhibited by s.c. injections of IFN
      gamma, and the rejection from IFN-gamma(+/+) mice was delayed after specific
      elimination of macrophages by intravenous (i.v.) injections of dichloromethylene
      diphosphonatecontaining liposomes. These results suggest an essential role of IFN
      gamma and involvement of macrophage in the rejection of CTL-resistant, virus
      infected cells.

PMID- 15957957
TI  - Importance of CD8(+)Vbeta8(+) T cells in IFN-gamma-mediated prevention of
      toxoplasmic encephalitis in genetically resistant BALB/c mice.
AB  - In our attempt to identify a major T cell population(s) that recognizes
      protective Toxoplasma gondii antigens and produces interferon-gamma (IFN-gamma)
      for prevention of toxoplasmic encephalitis (TE), we found T cell receptor
      Vbeta8(+) cells to be the most frequent IFN-gamma-producing population
      infiltrated into the brain of T. gondii-infected BALB/c mice genetically
      resistant to the disease. To examine the role of IFN-gamma production by this T
      cell population for resistance, we transferred Vbeta8(+) immune T cells purified
      from spleens of infected BALB/c and IFN-gamma(/) mice into infected, sulfadiazine
      treated, athymic nude mice. After discontinuation of sulfadiazine treatment,
      control nude mice that had not received any T cells and animals that had received
      Vbeta8(+) T cells from IFN-gamma(/) mice all died because of reactivation of
      infection (TE). In contrast, animals that had received the cells from BALB/c mice
      survived. Thus, IFN-gamma production by Vbeta8(+) T cells plays an important role
      in prevention of TE in these animals. When Vbeta8(+) immune T cells were divided
      into CD4(+) and CD8(+) subsets, a potent protective activity was observed only in
      the CD8(+) subset, whereas a combination of both subsets provided greater
      protection than did the CD8(+)Vbeta8(+) population alone. These results indicate
      that the CD8(+) subset of Vbeta8(+) T cells is a major afferent limb of IFN-gamma
      mediated resistance of BALB/c mice against TE, although the CD4(+) subset of the
      T cell population works additively or synergistically with the CD8(+)Vbeta8(+)
      population.

PMID- 15957958
TI  - Lentivirus-mediated transduction of PKR into CD34(+) hematopoietic stem cells
      inhibits HIV-1 replication in differentiated T cell progeny.
AB  - Previous studies from this laboratory evaluated the role of p68 kinase (PKR) in
      the control of HIV-1 replication via retrovirus-mediated gene transfer. PKR was
      studied because it is a key component of the interferon (IFN)-associated innate
      antiviral defense pathway in mammalian cells. In this study, CD34(+)
      hematopoietic stem cells (HSC) were transduced with an HIV-1-based lentiviral
      vector encoding the PKR transgene (pHIV-PIB) and cultured under conditions that
      support in vitro differentiation. With high-titer pseudotyped vector stocks, the
      histogram suggests 100% transduction of the HSC because the cells were
      blasticidin resistant. Analysis of transduced cells by hybridization revealed an
      average proviral vector copy number of 1.8 and 2.1 copies of vector sequence per
      cell. Increased PKR expression and activity (phosphorylation of eukaryotic
      initiation factor 2alpha [eIF2alpha]) were demonstrated in PKR-transduced,
      differentiated HSC. There was minimal reduction in cell viability and no
      induction of apoptosis after transduction of PKR. HSC transduced with the pHIV
      PIB lentiviral vector demonstrated normal differentiation into CD34-derived T
      cell progeny. Two days after HIV-1 infection, lentivirus-mediated transduction of
      PKR inhibited HIV-1 replication by 72% in T cell progeny compared with cells
      transduced with the empty vector control (pHIV-IB). By days 5 and 7 post-HIV-1
      infection, the surviving PKR-transduced cells were protected from HIV-1
      infection, as evidenced by a decrease in p24 antigen expression of at least two
      orders of magnitude. Our results demonstrate that PKR can be effectively
      delivered to HSC by a lentiviral vector and can protect CD34-derived T cell
      progeny from HIV-1 infection. These results provide support for application of
      the innate antiviral defense pathway in a gene therapy setting to the treatment
      of HIV-1 infection.

PMID- 15957960
TI  - Target achieved.

PMID- 15957961
TI  - Proton pump inhibitors may reduce tumour resistance.
AB  - Resistance to cytotoxic agents is a major problem in treating cancer. The
      mechanisms underlying this phenomenon appear to take advantage of functions
      involved in the control of cell homeostasis. A mechanism of resistance may be
      alteration of the tumour microenvironment via changes in the pH gradient between
      the extracellular environment and the cell cytoplasm. The extracellular pH of
      solid tumours is significantly more acidic than that of normal tissues, thus
      impairing the uptake of weakly basic chemotherapeutic drugs and reducing their
      effect on tumours. An option to revert multi-drug resistance is the use of agents
      that disrupt the pH gradient in tumours by inhibiting the function of pumps
      generating the pH gradient, such as vacuolar H(+)-ATPases (V-H(+)-ATPases). V
      H(+)-ATPases pump protons across the plasma membrane and across the membranes of
      various intracellular compartments. Some human tumour cells, particularly those
      selected for multi-drug resistance, exhibit enhanced V-H(+)-ATPase activity. A
      class of V-H(+)-ATPase inhibitors, called proton pump inhibitors (PPIs), have
      emerged as the drug class of choice for treating patients with peptic diseases.
      These drugs inhibit gastric acid secretion by targeting the gastric acid pump,
      but they also directly inhibit V-H(+)-ATPases. PPIs (including omeprazole,
      esomeprazole, lansoprazole, pantoprazole and rabeprazole) are protonable weak
      bases which selectively accumulate in acidic spaces. Recent findings from our
      group have shown that PPI pretreatment sensitised tumour cell lines to the effect
      of cisplatin, 5-fluoro-uracil and vinblastine. PPI pretreatment was associated
      with the inhibition of V-H(+)-ATPase activity and an increase of both
      extracellular pH and the pH of lysosomal organelles, consistent with a
      cytoplasmic retention of the cytotoxic drugs and targeting to the nucleus in the
      case of doxorubicin. In vivo experiments showed that oral pretreatment with
      omeprazole induced a sensitivity of the human solid tumours to anticancer drugs.

PMID- 15957962
TI  - Controversies in breast cancer: adjuvant and neoadjuvant therapy.
AB  - Initial randomised studies of chemotherapy and endocrine therapy showed that
      systemic treatments had a substantial impact on the survival of women with early
      breast cancer. The original assumption was that the efficacy of these treatments
      was limited to those patients presenting with more adverse prognostic features.
      Subsequently, meta-analyses of randomised trials revealed that the benefits of
      chemotherapy and endocrine therapy are not mutually exclusive and extend to all
      the prognostic subgroups. However, the absolute benefit varies according to
      baseline characteristics such as tumour stage and other biological factors. Over
      the last 10 years, considerable progress has been made with the introduction of
      new drugs into the adjuvant and neoadjuvant treatment of women with breast
      cancer. Taxanes and third-generation aromatase inhibitors are providing proof of
      additional benefits compared with standard reference treatments. In parallel,
      research on the biology of breast cancer is establishing novel prognostic and
      predictive factors, which may allow better treatment tailoring. Currently,
      however, women with early breast cancer and their doctors face the difficult task
      of making therapeutic decisions often based on early results from positive
      studies. In a disease where follow up is crucial to fully assess the benefit and
      long-term toxicities of an intervention, current knowledge leaves unanswered
      questions that generate debate and controversy. This review will summarise recent
      results from randomised trials of adjuvant and neoadjuvant therapy in women with
      early breast cancer and focus on the current controversies.

PMID- 15957963
TI  - The role of taxanes in the treatment of breast cancer.
AB  - Among the novel chemotherapeutic agents introduced in the last decade, the
      taxanes have emerged as the most powerful group of compounds, and results
      available so far confirm that they will be remembered in the future as the breast
      cancer chemotherapy of the 1990s. Two taxanes are available (paclitaxel and
      docetaxel) and they share some characteristics, although they do have some
      significant differences both in terms of their preclinical profile and, most
      importantly, their clinical characteristics. There are three main clinical
      differences: different efficacy-toxicity ratio in relation to dose and schedule;
      different integrability in anthracycline- and taxane-containing regimens,
      secondary to differences in pharmacokinetic interactions with anthracyclines; and
      different level of synergism between each taxane and trastuzumab. In clinical
      practice, the taxanes are now standard therapy in metastatic breast cancer. Their
      role as monochemotherapy or in combination with anthracyclines in advanced breast
      cancer has suggested their potential therapeutic impact in the treatment of
      patients with early breast cancer. Recent results in the adjuvant setting show
      that taxanes, used either in combination or in sequential therapy, possess the
      capability to induce significant improvements, in particular in terms of
      survival; thus confirming the positive impact of taxanes on the natural history
      of breast cancer. However, further results of all completed or ongoing Phase III
      trials in the early setting will help define the optimal use of taxanes and
      maximise the induced benefits for breast cancer patients.

PMID- 15957964
TI  - Treatment of hot flushes in breast and prostate cancer.
AB  - Hot flushes, the most common health problem reported by menopausal-age women, can
      lead to significant morbidity and affect the social life, ability to work and
      sleep pattern of the sufferer. Women treated for breast cancer and men receiving
      androgen ablation for prostate cancer experience hot flushes that are more
      frequent, severe and longer lasting than those experienced by the general
      menopausal population. In women with breast cancer, hot flushes can result from
      chemotherapy-induced menopause, hormonal therapy, or ovarian suppression. In men
      with prostate cancer, hot flushes occur after surgical or medical castration.
      Hormone replacement therapy with oestrogen-based compounds has been a mainstay of
      treatment for hot flushes during the perimenopausal period. However, recent
      studies have shown that, in healthy menopausal women, hormone replacement therapy
      is associated with an increased risk of breast cancer, myocardial infarction,
      thrombo-embolic events and stroke. Thus, identifying nonhormonal agents that can
      control hot-flush symptoms is essential to the quality of life of a growing
      population of cancer survivors. The most promising agents act on the CNS and
      include selective serotonin reuptake inhibitors, as well as venlafaxine and
      gabapentin.

PMID- 15957965
TI  - Monoclonal antibody therapy for central nervous system lymphomas: an emerging
      treatment paradigm.
AB  - The management of CNS lymphomas is poised for another revolution due to the
      emergence of therapeutic monoclonal antibodies. As the technology for generating
      monoclonal antibodies matures and obstacles are solved, therapeutic monoclonal
      antibodies will play an increasing role in the management of cancer. This article
      will review the biology of CNS lymphomas, monoclonal antibody technology,
      limitation of existing chemotherapies and the application of therapeutic
      monoclonal antibodies for the treatment of CNS lymphomas.

PMID- 15957966
TI  - Management of leptomeningeal malignancy.
AB  - Leptomeningeal carcinomatosis is defined as malignant infiltration of the pia
      matter and arachnoid membrane. Leukaemias and lymphomas, lung, breast cancer and
      melanoma are the primary tumours commonly associated with leptomeningeal
      carcinomatosis. Diagnosis is based on compatible symptoms and signs, cytological
      evidence of malignancy in the cerebrospinal fluid, and neuroimaging studies.
      Treatment is largely palliative (median survival 2-4 months). Patients with
      lympomatous or leukaemic meningitis, chemosensitive tumours such as breast
      cancer, low tumour burden, minimal neurological deficits, good performance status
      and controllable systemic disease survive longer with occasional long-term
      responses. Available treatment options include focal radiation therapy to CNS
      sites of bulky, symptomatic or obstructive meningeal deposits, intrathecal
      cytotoxic therapy and systemic chemotherapy. No evidence of superiority of
      intrathecal treatment compared with best palliative care (including radiation
      therapy and systemic treatment) is available from clinical trials. Novel
      treatment approaches include intrathecal liposomal Ara-C, the development of new
      cytotoxic compounds, signal transduction inhibitors and monoclonal antibodies for
      intrathecal or systemic use. Until data from multi-centre randomised trials are
      available, rationalisation of therapy should be done by stratifying patients to
      prognostic groups. High-risk patients will only survive for a few weeks and are
      better managed with supportive measures, whereas low-risk patients justify
      vigorous cerebrospinal fluid-directed treatment combined with radiation therapy
      and systemic chemotherapy.

PMID- 15957967
TI  - Current treatment options for myeloma.
AB  - In most cases multiple myeloma is an incurable plasma cell malignancy. Despite
      the use of conventional therapy or high-dose chemotherapy with autologous stem
      cell transplantation (ASCT), patients continue to relapse at a constant rate. A
      small minority of patients are cured by allogeneic transplantation. Novel drugs
      targeting not only the myeloma cell but also its interactions with the malignant
      microenvironment have recently been used in patients with relapsed/refractory
      disease. So far, ASCT has been the treatment of choice for eligible myeloma
      patients. However, many questions regarding the management of myeloma patients
      remain unanswered. How safe is ASCT in elderly patients? Is there a role for non
      myeloablative allogeneic transplantation in multiple myeloma? What is the role of
      novel agents, such as thalidomide, its analogues and bortezomib, in the treatment
      of newly diagnosed patients or as maintenance post-ASCT? This review summarises
      all available data for the current treatment options for myeloma providing a
      useful algorithm for its management.

PMID- 15957968
TI  - Review of current treatment practices for carcinoma of the head and neck.
AB  - The past two decades have witnessed a paradigm shift in the treatment of squamous
      cell carcinoma of the head and neck. Innovation in chemotherapy, radiotherapy and
      surgery has led to the assimilation of these modalities into our treatment
      algorithms. This modern multipart treatment plan has led to improved survival;
      however, this has come at the cost of increased toxicity. New and future
      therapies will be more tumour specific and, ideally, less toxic. Current research
      centres on these tumour-specific therapies with the anticipation of improved
      survival with decreased toxicity. This article will review the standard of care,
      recent advances and unfulfilled needs in the treatment of squamous cell carcinoma
      of the head and neck.

PMID- 15957969
TI  - Perspectives on novel therapies for bronchial carcinoma.
AB  - Improvements in conventional cytotoxic treatment have probably reached a plateau
      for the treatment of lung cancer; therefore, new treatment strategies that are
      based on a better understanding of tumour biology are required. Some progress has
      been made for non-small cell lung cancer, in which erlotinib (Tarceva, OSI-774;
      Genentech), an epidermal growth factor receptor antagonist, has demonstrated a
      significant clinical benefit in a Phase III randomised trial, and has been
      licensed for second- or third-line treatment. Other therapies under investigation
      include angiogenesis inhibitors, COX-2 inhibitors, retinoids, farnesyl
      transferase inhibitors, Bcl-2 inhibitors and c-Kit antagonists. In this article
      the recent and ongoing Phase II and III trials of these therapies in lung cancer
      are summarised, and the prospects for their further clinical development are
      discussed.

PMID- 15957970
TI  - Current chemotherapy options for thymic epithelial neoplasms.
AB  - Thymomas and thymic carcinoma are rare neoplasms. Surgical resection is the
      cornerstone of effective therapy. Stage I disease is effectively treated by
      complete surgical resection. The role of radiation therapy in completely resected
      stage II disease remains controversial. Adjuvant radiation therapy is useful for
      local control and may improve survival in patients with incompletely resected
      tumours. Cisplatin-based chemotherapy regimens play an important role in the
      treatment of advanced stage III/IV or recurrent disease thymomas, but have proven
      less effective for thymic carcinoma. Phase II trials of multimodality therapy
      incorporating neoadjuvant chemotherapy, surgery and postoperative radiation
      therapy show promise for unresectable disease. This review discusses recent
      clinical data and the potential role for agents targeting the epidermal growth
      factor receptor, angiogenesis and apoptotic pathways.

PMID- 15957971
TI  - Economic assessment on the management of chronic lymphocytic leukaemia.
AB  - In the last decade, several new promising treatments for chronic lymphocytic
      leukaemia (CLL) have been developed. Healthcare costs are increasing and new
      treatments tend to be very expensive; therefore, information about the cost
      effectiveness in treatments for CLL is urgently needed. The authors performed a
      literature review on the currently available economic evaluations on CLL
      treatments. A total of 65 articles were found, of which 11 could be included.
      These articles were evaluated on the basis of six methodological requirements for
      economic evaluations, enabling readers to judge the value of the studies. Only a
      small amount of information was available on the costs of CLL treatments. Future
      economic evaluations should be performed according to the methodological
      requirements for these studies, which should also be properly documented.

PMID- 15957973
TI  - An iontophoretic, fentanyl HCl patient-controlled transdermal system for acute
      postoperative pain management.
AB  - Patient-controlled modalities using intravenous or epidural routes have
      dramatically improved postoperative pain management. However, acute post
      operative pain continues to be undermanaged. Intravenous patient-controlled
      analgesia (PCA), the current standard of care for acute postoperative pain
      management, requires the patient to be attached to a staff-programmed pump
      apparatus via an intravenous catheter and tubing, rendering it invasive and
      mobility-limiting. An innovative, needle-free, iontophoretic, fentanyl HCl
      patient-controlled transdermal system (PCTS) is being developed for acute
      postoperative pain management. Fentanyl HCl PCTS is a compact, self-contained
      system that is easily applied to the upper outer arm or chest. It provides pain
      relief therapeutically equivalent to that of a standard regimen of morphine
      intravenous PCA, with pharmacokinetics similar to those of intravenous fentanyl
      infusion. Fentanyl HCl PCTS may be an effective, non-invasive alternative to
      currently available PCA modalities.

PMID- 15957972
TI  - Atorvastatin.
AB  - The introduction of statins has drastically changed the treatment and prevention
      of atherosclerotic vascular disease. By lowering lipid levels and reducing the
      risk of coronary heart disease, these drugs are among the most effective at
      reducing morbidity and mortality available to clinical practice. In fact, these
      compounds have demonstrated the reversible nature of the process of
      atherosclerosis and can be considered the most useful drugs we currently have in
      our armamentarium in the prevention of atherosclerosis and its clinical sequelae.
      Atorvastatin provides pronounced lipid lowering in a broad range of individuals
      with hypercholesterolaemia and, as such, is an appropriate first-line therapy for
      patients at low to high risk of coronary heart disease. Reductions in total and
      low-density lipoprotein cholesterol achieved with atorvastatin have been shown to
      translate into reductions in risk of cardiovascular morbidity and mortality in
      both primary and secondary prevention settings. Significant clinical benefits
      have specifically been observed among patients with Type 2 diabetes and in those
      with acute coronary syndromes. In common with other members of the statin class,
      atorvastatin is well tolerated, and adverse events are generally mild and
      transient in nature. Despite the significant clinical benefits provided by
      atorvastatin, its full potential in the management of atherosclerotic disease has
      yet to be wholly explored; however, studies currently ongoing will answer many of
      the outstanding questions.

PMID- 15957974
TI  - Voriconazole: review of a broad spectrum triazole antifungal agent.
AB  - Voriconazole is a second-generation triazole antifungal agent, structurally
      derived from fluconazole with an extended spectrum of activity against a wide
      variety of yeasts and moulds. Developed for the treatment of life-threatening
      fungal infections, it appears to be an effective therapy option for invasive
      aspergillosis, fluconazole-resistant candidiasis and refractory or less-common
      invasive fungal infections. It is available for both oral and intravenous
      administration and is characterised by an acceptable safety and tolerability
      spectrum.

PMID- 15957975
TI  - Capecitabine: effective oral fluoropyrimidine chemotherapy.
AB  - Fluoropyrimidine chemotherapy, principally with 5-fluorouracil (5-FU), has been a
      standard of care for a range of solid tumours for many years. Capecitabine, a
      precursor of 5-FU, is an oral fluoropyrimidine cytotoxic agent developed with the
      aim of providing a more effective, less toxic alternative to 5-FU, with the added
      advantage of oral administration. In clinical trials, capecitabine has proven to
      be an effective substitute for 5-FU in colorectal and breast cancer, and has
      become an accepted standard treatment in these tumours, both as a single agent
      and as a component of combination chemotherapy. It is also effective in a number
      of other solid tumours and as a radiosensitising agent. Capecitabine has
      significantly less serious toxicity than 5-FU when used alone or in combination
      with other cytotoxic agents. It has been shown to be resource saving in
      comparison with accepted standard comparator regimens in breast and colorectal
      cancer. Ongoing and future clinical trials will continue to examine, and are
      likely to expand, the role of capecitabine in the treatment of breast and
      colorectal cancer, as well as a number of other malignancies, both in the
      advanced palliative and adjuvant curative settings. This will involve the use of
      capecitabine as a single agent and increasingly in combination with other new
      anticancer agents.

PMID- 15957976
TI  - Clinical use of enoxaparin in the management of non-ST segment elevation acute
      coronary syndromes.
AB  - Enoxaparin (Lovenox; Roule-Poulenc Rorer, Inc.), a low molecular weight heparin
      (LMWH), is commonly used in the management of non-ST-segment elevation acute
      coronary syndromes (NSTE ACS) based on clinical trial outcomes. It is one of a
      group of glycosaminoglycan compounds that accelerate the inactivation of factor
      Xa by inducing a conformational change in antithrombin. In contrast to
      unfractionated heparin (UFH), LMWH have greater bioavailability, a more
      predictable anticoagulant response, longer half-life and a higher proportion of
      anti-factor Xa to anti-factor IIa activity. As a consequence, laboratory
      monitoring of the anticoagulant effect is typically unnecessary. Antithrombin
      therapy with LMWH or UFH has the highest-level recommendation (IA) in the 2002
      professional guidelines for the management of unstable angina and non-ST
      elevation myocardial infarction, where enoxaparin has a IIA recommendation over
      UFH unless early coronary artery bypass surgery is planned. In a recent
      systematic overview of > 20,000 patients with NSTE ACS from six clinical trials,
      including conservative and invasively managed patients, enoxaparin provided a
      statistically significant reduction in 30-day death or nonfatal myocardial
      infarction (MI) compared with UFH with no significant excess in transfusions, or
      major bleeding. These data support the role of enoxaparin as an anti-coagulant in
      patients with NSTE ACS.

PMID- 15957977
TI  - Aspirin and esomeprazole are superior to clopidogrel in preventing recurrent
      ulcer bleeding.
AB  - Although low-dose aspirin is commonly used as the antiplatelet agent to prevent
      ischaemic events such as myocardial infarction and stroke, clopidogrel is
      probably superior at preventing ischaemic events. For patients who cannot
      tolerate aspirin, adding a proton pump inhibitor or substituting clopidogrel are
      options. Patients with endoscopy-confirmed ulcer healing were assigned to
      clopidogrel 75 mg/day or aspirin 80 mg/day and esomeprazole 20 mg b.i.d. for 12
      months. There were 14 confirmed cases of recurrent ulcer bleeding, with 13 being
      from the 161 patients taking clopidogrel and 1 from the 159 patients taking
      aspirin plus esomeprazole. This trial has clearly shown that the combination of
      aspirin and esomeprazole is superior to clopidogrel in preventing recurrent ulcer
      bleeding. A more interesting study may have been to compare the effects of
      aspirin and clopidogrel in the presence of esomeprazole in patients with a
      history of ulcers.

PMID- 15957978
TI  - Selected highlights from the 27th San Antonio Breast Cancer Symposium. San
      Antonio, TX, USA, 8-11 December 2004.
AB  - The San Antonio Breast Cancer Symposium is now considered the most important
      international breast cancer meeting worldwide. On 8-11th December 2004,
      approximately 6700 participants attended the meeting and shared the latest
      findings from breast cancer research. All the main fields of breast cancer
      research and treatment were covered. This report will focus on the most relevant
      advancements in the pharmacotherapy of breast cancer. The selected presentations
      have been grouped together in separate sections, including the fields of
      prevention, early disease and advanced disease. The most promising data from
      translational research have also been included, with particular regard to those
      who will most likely influence the management of breast cancer patients in the
      future.

PMID- 15957979
TI  - Selected highlights from the 5th International Conference on Ovarian Cancer.
      Houston, TX, USA, 1-4 December 2004.

PMID- 15957982
TI  - Dr John Sims. A mystery solved.

PMID- 15957980
TI  - Identification and characterization of molecular interactions between
      mortalin/mtHsp70 and HSP60.
AB  - Mortalin/mtHsp70 (mitochondrial Hsp70) and HSP60 (heat-shock protein 60) are heat
      shock proteins that reside in multiple subcellular compartments, with
      mitochondria being the predominant one. In the present study, we demonstrate that
      the two proteins interact both in vivo and in vitro, and that the N-terminal
      region of mortalin is involved in these interactions. Suppression of HSP60
      expression by shRNA (short hairpin RNA) plasmids caused the growth arrest of
      cancer cells similar to that obtained by suppression of mortalin expression by
      ribozymes. An overexpression of mortalin, but not of HSP60, extended the in vitro
      lifespan of normal fibroblasts (TIG-1). Taken together, this study for the first
      time delineates: (i) molecular interactions of HSP60 with mortalin; (ii) their co
      and exclusive localizations in vivo; (iii) their involvement in tumorigenesis;
      and (iv) their functional distinction in pathways involved in senescence.

PMID- 15957983
TI  - Female reproductive history and the skeleton-a review.

PMID- 15957984
TI  - Symptoms associated with diagnosis of ovarian cancer: a systematic review.

PMID- 15957985
TI  - Economic modelling of antenatal screening and ultrasound scanning programmes for
      identification of fetal abnormalities.
AB  - OBJECTIVE: Within the framework of a health technology assessment and using an
      economic model, to determine the most clinically and cost effective policy of
      scanning and screening for fetal abnormalities in early pregnancy. DESIGN: A
      discrete event simulation model of 50,000 singleton pregnancies. SETTING:
      Maternity services in Scotland. POPULATION: Women during the first 24 weeks of
      their pregnancy. METHODS: The mathematical model was populated with data on
      uptake of screening, prevalence, detection and false positive rates for eight
      fetal abnormalities and with costs for ultrasound scanning and serum screening.
      Inclusion of abnormalities was based on the relative prevalence and clinical
      importance of conditions and the availability of data. Six strategies for the
      identification of abnormalities prenatally including combinations of first and
      second trimester ultrasound scanning and first and second trimester screening for
      chromosomal abnormalities were compared. MAIN OUTCOME MEASURES: The number of
      abnormalities detected and missed, the number of iatrogenic losses resulting from
      invasive tests, the total cost of strategies and the cost per abnormality
      detected were compared between strategies. RESULTS: First trimester screening for
      chromosomal abnormalities costs more than second trimester screening but results
      in fewer iatrogenic losses. Strategies which include a second trimester
      ultrasound scan result in more abnormalities being detected and have lower costs
      per anomaly detected. CONCLUSIONS: The preferred strategy includes both first and
      second trimester ultrasound scans and a first trimester screening test for
      chromosomal abnormalities. It has been recommended that this policy is offered to
      all women in Scotland.

PMID- 15957986
TI  - Outcomes of severe pre-eclampsia/eclampsia in Yorkshire 1999/2003.
AB  - OBJECTIVE: To establish the risk of serious complications from severe pre
      eclampsia and eclampsia in a region using a common guideline for the management
      of these conditions. DESIGN: A five-year prospective study. SETTING: Sixteen
      maternity units in Yorkshire. POPULATION: All women managed with severe pre
      eclampsia and eclampsia. METHODS: A common guideline was developed for the
      management of women with these conditions. A network of midwives prospectively
      collected outcome data. MAIN OUTCOME MEASURE: Incidence of the conditions and
      serious complication rates. RESULTS: A total of 210,631 women delivered in the 16
      units between 1 January 1999 and 31 December 2003. One thousand eighty-seven
      women were diagnosed with severe pre-eclampsia or eclampsia (5.2/1000). One
      hundred and fifty-one women had serious complications including 82 women
      (39/10,000) having eclamptic seizures and 49 women (23/10,000) requiring ICU
      admission. There were no maternal deaths but 54 out of 1145 babies died before
      discharge, giving a mortality rate of 47.2/1000. Of the 82 cases of eclampsia, 45
      occurred antenatally (55%), 18 before admission to the maternity unit. Eleven
      cases occurred in labour (13%), including 1 during a caesarean section, and 26
      cases occurred following delivery (32%). Twenty-five women developed pulmonary
      oedema (2.3% of cases) and six women required renal dialysis (0.55% of cases).
      One hundred and sixty-five (15%) required no antihypertensive therapy and 489
      (53%) of the remainder required only oral therapy. Two hundred and one (18.5%)
      required more than one drug. CONCLUSION: A regional guideline for severe pre
      eclampsia and eclampsia can be developed and implemented. Its use may contribute
      to a low rate of serious complications.

PMID- 15957987
TI  - Increasing likelihood of further live births in HIV-infected women in recent
      years.
AB  - OBJECTIVE: To examine how the subsequent childbearing of HIV-infected mothers
      enrolled in the European Collaborative Study (ECS) has changed over time and
      identify factors predictive of further childbearing. DESIGN: Prospective cohort
      study. SETTING: Centres in nine European countries included in the ECS, enrolled
      between end 1986 and November 2003. POPULATION: HIV-infected women (3911): 3693
      with only one and 218 with subsequent live births. METHODS: Univariable and
      multivariable logistic regression analyses to obtain odds ratios (OR) and 95%
      confidence intervals (CI). Kaplan-Meier (KM) analyses to estimate cumulative
      proportions of women having a subsequent live birth. MAIN OUTCOME MEASURES:
      Subsequent live birth. RESULTS: In multivariable analysis adjusting for time
      period, ethnicity, maternal age and parity, black women were more likely
      [adjusted odds ratio (AOR) 2.45; 95% CI, 1.75-3.43], and women >30 years less
      likely (AOR 0.54, 0.37-0.80), to have a subsequent live birth. Time to subsequent
      live birth significantly shortened over time, with an estimated 2% of women
      having a subsequent live birth within 24 months of enrollment pre-1989 versus 14%
      in 2000-2003 (P < 0.001). Estimated time to subsequent live birth was shorter for
      black than for white women (P < 0.001). CONCLUSIONS: The likelihood of subsequent
      live births substantially increased after 1995 and birth intervals were shorter
      in women on HAART and among black women. Numbers are currently too small to
      address the issue of advantages and disadvantages in the management of subsequent
      deliveries.

PMID- 15957988
TI  - The effects of pregnancy on the cardiovascular response to acute systemic
      isocapnic hypoxia in conscious sheep.
AB  - OBJECTIVE: This study tested the hypothesis that pregnancy affects the
      cardiovascular responses to hypoxia by altering the outputs of the peripheral
      components of the stress system and independent of changes in P(a)CO(2). DESIGN:
      Comparison of cardiovascular and endocrine responses to acute isocapnic hypoxia
      between pregnant and non-pregnant ewes. SETTING: Experimental laboratory. SAMPLE:
      Fifteen pregnant (118 days of gestation; term is ca. 145 days) and 8 non-pregnant
      sheep. METHODS: Chronically instrumented pregnant and non-pregnant ewes were
      subjected to 1 hour normoxia, 1 hour of acute systemic isocapnic hypoxia and 1
      hour recovery. MAIN OUTCOME MEASURES: Arterial blood pressure, heart rate,
      femoral blood flow and femoral vascular conductance were recorded continuously
      throughout and arterial blood samples were taken during normoxia, hypoxia and
      recovery for the measurement of blood gas, metabolic and endocrine status.
      RESULTS: Basal blood pressure and blood glucose and lactate concentrations were
      lower in pregnant animals (P < 0.05). In contrast, basal cardiovascular variables
      and plasma concentrations of noradrenaline, adrenaline, neuropeptide Y,
      adrenocorticotropic hormone (ACTH) and cortisol were similar in pregnant and non
      pregnant ewes. During hypoxia similar reductions in P(a)O(2) occurred in pregnant
      and non-pregnant animals, without alterations in P(a)CO(2) or pH(a). In non
      pregnant ewes, acute hypoxia induced a transient increase in arterial pressure
      and sustained tachycardia without significant changes in femoral haemodynamics.
      Pregnancy attenuated the cardiovascular response, significantly diminishing the
      magnitude of the increment in heart rate throughout the hypoxic challenge (P <
      0.001). However, hypoxia did not induce significant changes in blood metabolites
      or in plasma concentrations of any stress hormone measured in either pregnant or
      non-pregnant animals. CONCLUSION: Pregnancy not only affects basal but also
      stimulated cardiovascular function in the mother. The diminished chronotropic
      response to hypoxia in pregnancy is mediated via mechanisms independent of
      changes in P(a)CO(2) or in plasma concentrations of hormones or metabolites
      associated with activation of the stress system.

PMID- 15957989
TI  - The arterial system in pre-eclampsia and chronic hypertension with superimposed
      pre-eclampsia.
AB  - OBJECTIVES: To determine if the normal gestational changes in mechanical
      properties of the arterial system are altered in pre-eclampsia. DESIGN:
      Prospective controlled observational study. SETTING: University urban tertiary
      medical centre. POPULATION: Eleven pre-eclamptics and 10 chronic hypertensives
      with superimposed pre-eclampsia were compared with 14 normotensive gravidas
      experiencing preterm labour, all receiving MgSO(4). Two additional control groups
      were studied as well: (A) nine normal pregnant women receiving neither magnesium
      nor epidural, for baseline comparisons; and (B) eight normotensive gravidas
      receiving epidural anaesthesia. METHODS: Two-dimensional targeted M-mode
      echocardiograms and continuous wave Doppler velocity were used to obtain
      instantaneous pressure and flow data. Total vascular resistance (TVR) quantified
      the steady component of systemic arterial load; pulsatile arterial load was
      characterised by global arterial compliance (AC), aortic input impedance spectrum
      (Z(1)) and characteristic impedance (Z(0)). MAIN OUTCOME MEASURES: TVR, AC, Z(1),
      Z(0). RESULTS: Controls, pre-eclamptics and chronic hypertensives with
      superimposed pre-eclampsia, respectively: TVR index 1328 [299], 1973 [609]*, 2428
      [562]*(,#) dyn second cm(-5) m(2); AC area index 1.69 [0.46], 1.19 [0.46]*, 0.93
      [0.38]* mL mmHg(-1) m(-2); Z(0) index 253.2 [61.3], 327.0 [135.1], 307.5 [130.9]
      dyn second cm(-5) m(2); and Z(1) index 184.2 [56.5], 283.6 [81.6]*, 357.1
      [119.5]* dyn second cm(-5) m(2) (*P < 0.05 vs control;(#)P < 0.05 vs pre
      eclampsia). Normal gravidas (in secondary controls group A) had decreased mean
      systolic and diastolic blood pressures, and increased AC and cardiac indices,
      compared with women receiving magnesium tocolysis, verifying the need for these
      primary controls. No differences were noted between normotensive gravidas
      receiving epidural anaesthesia (secondary controls group B) and the non
      anesthetised controls (group A), eliminating epidural as a confounder.
      CONCLUSIONS: The normal gestational changes in systemic arterial mechanical
      properties are significantly altered in pre-eclampsia and these alterations are
      more marked with superimposed hypertensive disease.

PMID- 15957990
TI  - Pregnancy outcome after maternal organ transplantation in Sweden.
AB  - OBJECTIVE: To study pregnancy outcome before and after organ transplantation.
      DESIGN: Registry study. SETTING: Swedish Health Registers. POPULATION: All births
      in Sweden 1973-2002. METHODS: Women who had organ transplantation were identified
      from the Hospital Discharge Register and their deliveries before and after the
      transplantation were identified from the Medical Birth Register. Abortions
      requiring hospitalisation were identified from the Hospital Discharge Register.
      Outcomes were compared with those in the total population. Adjustments were made
      for maternal age, parity and smoking habits. MAIN OUTCOME MEASURES: Miscarriage,
      preterm delivery, low birthweight, small for gestational age, congenital
      malformations, infant death, pre-eclampsia and placental abruption. RESULTS: A
      total of 980 infants born before and 152 born after transplantation were
      identified. A high frequency of pre-eclampsia (22%), preterm birth (46%), low
      birthweight (41%), small for gestational age (16%) and infant death (5% before
      the age of one) were found for deliveries after transplantation but similar
      frequencies were found also among deliveries a few years before transplantation.
      No significant increase in congenital malformation rate was seen. Among 15
      infants born after liver transplantation, 2 were malformed. CONCLUSIONS:
      Pregnancies after organ transplantation have an increased risk of complications
      but this is similar to pregnancies occurring before the transplantation.

PMID- 15957991
TI  - Morbidity and development in childhood of infants born after temporising
      treatment of early onset pre-eclampsia.
AB  - OBJECTIVE: To assess morbidity and development in childhood of infants born after
      temporising management of severe early onset pre-eclampsia. DESIGN: Cohort study
      with matched controls. SETTING: University centre for high risk obstetrics.
      SAMPLES: Three groups of neonates matched for gender and year of birth: one born
      after temporising treatment of severe early onset (<32 weeks) pre-eclampsia with
      an average delay of delivery of two weeks (n= 193); one born at the duration of
      pregnancy [1 week] of the pre-eclamptic mother on admission (control group I, n =
      192); and one born at the same gestational age [1 week] as the infant of the pre
      eclamptic mother (control group II, n= 189). METHOD: Follow up at four years of
      age or more using medical records and questionnaires. MAIN OUTCOME MEASURES: The
      presence of various morbidities including mental retardation, cerebral palsy,
      motor skill problems, visual handicap, hearing loss, speech and language
      problems, education level and acute or chronic respiratory problems. RESULTS:
      Median follow up of seven years (range 4-12) was achieved in 159 infants in the
      study group (83%), 122 in control group I (64%) and 110 in control group II
      (58%). Missing data analysis showed no differences in neonatal characteristics
      and morbidity between infants with and without follow up in the study group. All
      major and minor handicaps were less frequent in the study group than in control
      group I but statistical significance was reached only for acute and chronic
      respiratory disorders in the study group (13.8%) compared with control group I
      (27%). CONCLUSION: Average delay of delivery of two weeks with temporising
      management in severe early onset pre-eclampsia is associated with a reduced risk
      of respiratory disorders in childhood.

PMID- 15957992
TI  - An accurate automated blood pressure device for use in pregnancy and pre
      eclampsia: the Microlife 3BTO-A.
AB  - OBJECTIVE: To assess the accuracy of an automated blood pressure device
      (Microlife 3BTO-A) in pregnancy and pre-eclampsia according to the British
      Hypertension Society (BHS) protocol. DESIGN: Prospective observational study.
      SETTING: Antenatal ward and clinics at Guy's and St Thomas' Hospital, London, UK.
      POPULATION: One hundred and five pregnant women including 35 women with non
      proteinuric hypertension and 35 with pre-eclampsia. METHODS: Two trained
      observers took nine sequential same-arm measurements from each woman.
      Measurements alternated between a mercury sphygmomanometer and the device. MAIN
      OUTCOME MEASURES: Grading criteria of the BHS protocol (A/B grade = pass; C/D
      grade = fail). RESULTS: The device passed the BHS protocol by achieving an A/B
      grade. It also achieved criteria of the Association for the Advancement of
      Medical Instrumentation for systolic and diastolic pressures respectively, in
      normotensive [-0.5 (5.7) mmHg; -0.07 (7.7) mmHg], non-proteinuric hypertensive [
      3.3 (6.9) mmHg; -2.4 (6.6) mmHg] and pre-eclamptic pregnancy [-4.1 (6.4) mmHg; 
      1.3 (7.9) mmHg]. CONCLUSION: The Microlife 3BTO-A can be recommended for use in a
      pregnant population, including pre-eclampsia, according to the BHS protocol.

PMID- 15957993
TI  - Stress responses at birth: determinants of cord arterial cortisol and links with
      cortisol response in infancy.
AB  - OBJECTIVE: To investigate (A) the determinants of infant stress response at
      delivery and (B) test the hypothesis that stress at birth, as reflected by cord
      arterial cortisol, influences cortisol response to vaccination at two months.
      DESIGN: Prospective observational study. SETTING: Tertiary referral maternity
      hospital. POPULATION: One hundred and seventy-two primiparous women with
      uncomplicated singleton pregnancies. METHODS: Women were recruited antenatally.
      At birth, cord arterial blood and obstetric data were collected. Saliva was
      collected from infants immediately before and after vaccination at two months.
      Cortisol was analysed from cord blood and saliva by radio-immunoassay. MAIN
      OUTCOME MEASURES: Stress response at birth, as demonstrated by cord arterial
      cortisol; association with saliva cortisol response to vaccination at two months.
      RESULTS: Cord arterial cortisol varied with mode of delivery, combined
      spinal/epidural use and pH. Salivary cortisol response at two months correlated
      with cord arterial cortisol (r= 0.24, P < 0.05). Infants with the highest and
      lowest cord arterial cortisol had markedly different cortisol responses at two
      months (P= 0.017). These groups had different modes of delivery with caesarean
      rates of <8% in the high cortisol response group and 83% in the low cortisol
      response group (P < 0.0001). CONCLUSION: Babies born vaginally mount greater
      cortisol responses at birth than those delivered by caesarean section. Stress at
      delivery may influence the infant HPA axis response for up to two months.

PMID- 15957994
TI  - The impact of intrapartum analgesia on infant feeding.
AB  - OBJECTIVE: To investigate the impact of intrapartum analgesia on infant feeding
      at hospital discharge. DESIGN: Retrospective cohort. SETTING: Maternity unit of a
      UK district general hospital. POPULATION: A random sample of 425 healthy
      primiparae delivering healthy singleton babies at term in 2000. METHODS: A random
      sample of primiparae delivering term neonates was identified from the birth
      register. We retrieved and analysed the corresponding joint midwifery/obstetric
      case notes. MAIN OUTCOME MEASURE: Infant feeding method at discharge from
      hospital. RESULTS: Women [190/424 (45%)] were exclusively bottle feeding their
      babies at discharge from hospital. No one commenced breastfeeding after hospital
      discharge. Regression analysis revealed that the main determinants of bottle
      feeding were as follows: maternal age [odds ratio (OR) 0.90, 95% confidence
      interval [CI] 0.85-0.95 per year]; occupation (OR 0.63, 95% CI 0.40-0.99 for each
      category, unemployed, manual, non-manual); antenatal feeding intentions (OR 0.12,
      95% CI 0.080-0.19 for each category, bottle feeding, undecided, breastfeeding);
      caesarean section (OR 0.25, 95% CI 0.13-0.47, caesarean or vaginal delivery); and
      dose of fentanyl administered intrapartum (OR 1.004, 95% CI 1.000-1.008, 90% CI
      1.001-1.007 for each microgram administered, range 8-500 mug). CONCLUSIONS: A
      dose-response relationship between fentanyl and artificial feeding has not been
      reported elsewhere. When well-established determinants of infant feeding are
      accounted for, intrapartum fentanyl may impede establishment of breastfeeding,
      particularly at higher doses.

PMID- 15957995
TI  - Neonatal death after hypoxic ischaemic encephalopathy: does a postmortem add to
      the final diagnoses?
AB  - BACKGROUND: Case review after fatal perinatal asphyxia may have medicolegal
      implications. Accurate diagnosis of cause of death is therefore essential.
      OBJECTIVE: To determine consent rate and utility of autopsy after fatal grade III
      hypoxic ischaemic encephalopathy (HIE) presumed to be secondary to birth
      asphyxia. DESIGN: A retrospective clinical review from January 1995 to December
      2002. SETTING: Regional tertiary referral neonatal unit, Wellington, New Zealand.
      POPULATION: Inclusion criteria were gestation >/=37 weeks, resuscitation after
      delivery and clinical course of grade III HIE. Exclusions were a recognised major
      lethal malformation. METHODS: Review of clinical records including the autopsy
      report. MAIN OUTCOME MEASURES: Consent for autopsy, change in diagnosis after
      autopsy. RESULTS: Twenty-three infants died during the time period with a major
      diagnosis of grade III HIE. Three did not meet inclusion criteria. Of the
      remaining 20, 11 were female. Median gestation at birth was 40 weeks (range 38-42
      weeks) and median birth weight was 3568 g (range 2140-4475 g). In 8/17 of the
      infants for whom length and head measurements were available, the Ponderal Index
      suggested intrauterine growth retardation. The 16/20 infants had an autopsy. Four
      of these were Coroner's cases giving an autopsy rate of 80% with a rate by
      consent of 60%. In 10 (62.5%) infants, significant new information was added to
      the clinical diagnoses. CONCLUSIONS: Neonatal HIE is a symptom rather than a
      final clinical diagnosis. A full autopsy is required to fully explore the reasons
      for fatal neonatal HIE and may provide information that is important
      medicolegally.

PMID- 15957996
TI  - Cohort study of maternal and neonatal morbidity in relation to use of episiotomy
      at instrumental vaginal delivery.
AB  - OBJECTIVE: The aim of this study was to investigate the maternal and neonatal
      morbidity related to use of episiotomy for vacuum and forceps deliveries. DESIGN:
      Retrospective population-based cohort study. SETTING: Dundee, Scotland.
      POPULATION: Two thousand one hundred and fifty three women who experienced an
      instrumental vaginal delivery between January 1998 and December 2002. METHODS:
      Univariate and multivariate logistic regression analyses were performed comparing
      deliveries with and without the use of episiotomy. MAIN OUTCOME MEASURES:
      Extensive perineal tears (third and fourth degree) and shoulder dystocia.
      RESULTS: Two hundred and forty-one (11%) of the 2153 women who underwent
      instrumental vaginal deliveries did not receive an episiotomy. Vacuum delivery
      was associated with less use of episiotomy compared with forceps (odds ratio
      0.10, 95% CI 0.07-0.14). Extensive perineal tears were more likely with use of
      episiotomy (7.5%vs 2.5%, adjusted OR 2.92, 95% CI 1.27-6.72) as was neonatal
      trauma (6.0%vs 1.7%, adjusted OR 2.62, 95% CI 1.05-6.54). Use of episiotomy did
      not reduce the risk of shoulder dystocia (6.9%vs 4.6%, adjusted OR 1.43, 95% CI
      0.74-2.76). The findings were similar for delivery by vacuum and forceps.
      CONCLUSION: The use of episiotomy increased the risk of extensive perineal tears
      without a reduction in the risk of shoulder dystocia.

PMID- 15957997
TI  - The expression of matrix metalloproteinase-9 in human follicular fluid is
      associated with in vitro fertilisation pregnancy.
AB  - OBJECTIVE: To investigate the role of matrix metalloproteinase-9 (MMP-9) in the
      pre-ovulatory follicular fluid and culture media during in vitro fertilisation
      (IVF) cycle and to develop the zymographic pre-diagnosis marker for successful
      implantation and pregnancy in human IVF. DESIGN: Controlled clinical study.
      SETTING: IVF Laboratory, Women's Hospital Infertility Clinic and Dongguk
      University, Korea. SAMPLE: Women undergoing in vitro fertilisation treatment.
      METHODS: Experiments were designed for controlled clinical study with women
      undergoing IVF treatment. MMP-9 expressions in follicular fluid and culture media
      samples that had been collected during transvaginal oocyte retrieval were
      measured using zymography. MMP-9 activities and expressions were strongly
      correlated to a higher rate of fertilisation and pregnancy. MAIN OUTCOME
      MEASURES: Fertilisation rates and ultrasonic evidence of intrauterine pregnancy
      by four weeks after embryo transfer. RESULT: MMP-9 activity was significantly
      higher in the pregnant group than in the non-pregnant group (P < 0.01). In
      contrast, MMP-2 activity was present in the follicular fluid and culture media of
      all women, and no difference in its expressions was found between the pregnant
      and non-pregnant groups. No correlation was found between the MMP-9 expression in
      follicular fluid and culture media and the fertilisation rates. CONCLUSION: The
      expression of MMP-9 in the follicular fluid and culture media is a prerequisite
      for successful pregnancy in IVF cycle. The zymography of MMP-9 activity in
      follicular fluids of human and culture media was developed as a pre-diagnostic
      method and zymographic diagnosis marker for successful fertilisation,
      implantation and pregnancy in human IVF.

PMID- 15957998
TI  - Elevated levels of CRP in ovarian hyperstimulation syndrome: an unrecognised
      potential hazard?
AB  - OBJECTIVE: Elevated levels of C-reactive protein (CRP) were found recently to be
      a crucial marker for cardiovascular disease. This protein might have a role in
      endothelial cell activation, vascular damage and a thrombotic tendency. We sought
      to determine whether concentrations of CRP are altered in women with controlled
      ovarian hyperstimulation (COH) or hyperstimulation syndrome (OHSS). DESIGN: A
      prospective cohort study. SETTING: The gynecology department and IVF unit of the
      Lis maternity hospital. POPULATION: Twenty women with OHSS, 20 women undergoing
      COH and 20 women who participated as controls were included in the study.
      METHODS: Venous blood was withdrawn for analysis of high sensitive C-reactive
      protein (hs-CRP) using the Boering BN-II nephelometer. MAIN OUTCOME MEASURES: hs
      CRP levels were determined. RESULTS: There was a significant (P < 0.05)
      difference in the hs-CRP concentrations in women with OHSS compared with women
      with COH and controls. The respective values for hs-CRP were 19.0 [4.0], 7.0
      [1.7] and 4.6 [1.1] mg/L. CONCLUSIONS: Women with OHSS have elevated
      concentrations of hs-CRP. This finding, previously believed to merely represent
      an acute phase response, may actually represent a yet unrecognised
      pathophysiological factor of this syndrome and pave the way for new
      investigational directions of this potentially hazardous condition.

PMID- 15957999
TI  - The association of hysterectomy and menopause: a prospective cohort study.
AB  - OBJECTIVE: To determine whether or not hysterectomy leads to an earlier onset of
      the menopause. DESIGN: A prospective cohort study. SETTING: Gynaecology service
      of large urban hospital. POPULATION: Premenopausal women with and without
      hysterectomy. METHODS: Multivariate survival analysis techniques were used to
      adjust for differences in initial follicle stimulating hormone (FSH) levels, body
      mass index, smoking and unilateral oophorectomy between the groups. MAIN OUTCOME
      MEASURES: FSH levels were measured for five years following hysterectomy and
      compared with the comparison group. Menopause was defined as a single FSH
      measurement of at least 40 IU/L. RESULTS: Two hundred and fifty-seven women
      undergoing hysterectomy were compared with 259 women who had not undergone a
      hysterectomy. Fifty-three women (20.6%) in the hysterectomy group and 19 women
      (7.3%) in the comparison group reached menopause over the five years of the
      study. Women in the hysterectomy group with a pre-operative FSH <10 IU/L reached
      menopause 3.7 years (95% CI 1.5-6.0 years) earlier than women in the comparison
      group independent of BMI, smoking and unilateral oophorectomy. Twenty-eight women
      in the hysterectomy group had unilateral oophorectomy and 10 (35.7%) of these
      women reached menopause over the five years of follow up. Women in the
      hysterectomy group with unilateral oophorectomy reached menopause 4.4 years (95%
      CI 0.6, 7.9 years) earlier than women with both ovaries in the hysterectomy group
      independent of baseline FSH, BMI and smoking. CONCLUSIONS: Hysterectomy is
      associated with an earlier onset of menopause. Hysterectomy with unilateral
      oophorectomy is associated with an even earlier onset of the menopause in this
      study.

PMID- 15958000
TI  - Outpatient hysteroscopy: traditional versus the 'no-touch' technique.
AB  - OBJECTIVE: To assess whether outpatient hysteroscopy using the 'no-touch'
      technique confers any advantages in terms of patient discomfort over the
      traditional technique. DESIGN: Prospective randomised controlled study. SETTING:
      Outpatient hysteroscopy clinic in a large university undergraduate teaching
      hospital. POPULATION: All women referred for outpatient hysteroscopy in a 12
      month period. INTERVENTIONS: Women were randomised to undergo either traditional
      saline hysteroscopy requiring the use of a speculum and tenaculum, or a 'no
      touch' vaginoscopic hysteroscopy which does not require a speculum or tenaculum.
      Each group was further subdivided to have hysteroscopy with either a 2.9-mm or 4
      mm hysteroscope. Patients were asked to complete pre- and postprocedure
      questionnaires ranking pain scores. MAIN OUTCOME MEASURES: The relative success
      of each of these techniques, requirement for local anaesthetic and pain scores at
      different times during the hysteroscopy were recorded at the end of the
      procedure. The time taken to carry out each procedure was also measured. RESULTS:
      One hundred and twenty women were recruited in this study: 60 were randomised to
      traditional hysteroscopy and 60 to 'no-touch' hysteroscopy. The overall success
      rate for hysteroscopy was 99%. There was no significant difference in the
      requirement for local anaesthetic between the two groups, but those who underwent
      'no-touch' hysteroscopy with a 2.9-mm hysteroscope had the lowest requirement of
      local anaesthetic (10% compared with 27% in the no-touch hysteroscopy with a 4-mm
      hysteroscope group). The time taken to perform hysteroscopy and biopsy was
      significantly shorter with 'no-touch' hysteroscopy (5.9 vs 7.8 min; difference
      1.9, 95% CI 0.7-3.1). There were no differences in pain scores between the groups
      at different times during hysteroscopy. CONCLUSIONS: 'No-touch' or vaginoscopic
      hysteroscopy is significantly faster to perform than the traditional technique.
      Although there was no difference in pain scores between the two techniques, local
      anaesthetic requirements were least in those who underwent 'no-touch'
      hysteroscopy with a narrow bore hysteroscope.

PMID- 15958001
TI  - Randomised controlled trial of LigaSure versus conventional suture ligature for
      abdominal hysterectomy.
AB  - OBJECTIVE: To compare the use of LigaSure with conventional suture ligature in
      abdominal hysterectomy. DESIGN: Pilot randomised controlled unblinded trial with
      block randomisation according to three operating surgeons. SETTING: One Norwegian
      teaching hospital, Department of Gynaecology and Obstetrics. SAMPLE: Thirty women
      who underwent total or subtotal abdominal hysterectomy. METHODS: Data, with
      regard to operation time expenditure and the occurrence of peri- and post
      operative complications, were collected and compared between the two techniques.
      MAIN OUTCOME MEASURES: Operation time, peri- and post-operative complications.
      RESULTS: Mean operation duration was 61.7 minutes with LigaSure and 54.5 minutes
      with conventional suture ligature. The corresponding operative blood loss was 303
      and 298 mL, respectively. Occurrence of complications was few and not
      significantly different between the two techniques. Mean hospital stay was longer
      following LigaSure operations (10 vs 6 days), probably due to a certain age
      imbalance between the study groups. CONCLUSIONS: Within the limitation of this
      pilot study, we did not uncover a time sparing effect from the use of LigaSure or
      any difference in the occurrence of blood loss and complications.

PMID- 15958002
TI  - The relationship of vaginal prolapse severity to symptoms and quality of life.
AB  - OBJECTIVE: To assess the relationship and location of vaginal prolapse severity
      to symptoms and quality of life. DESIGN: A prospective observational study.
      SETTING: Urogynaecology Unit, Imperial College, St Mary's Hospital, London.
      POPULATION: Women with and without symptoms of vaginal prolapse. METHODS: All
      women completed a validated Prolapse Quality of Life (P-QOL) questionnaire. This
      included a urinary, bowel and sexual symptom questionnaire. All women were
      examined using the Pelvic Organ Prolapse Quantification system (POP-Q). POP-Q
      scores in those with and without prolapse symptoms were compared. Urinary and
      bowel symptoms and sexual function were compared and related to prolapse severity
      and location. MAIN OUTCOME MEASURES: POP-Q scores, P-QOL scores, urinary and
      bowel symptoms and sexual function. RESULTS: Three hundred and fifty-five women
      were recruited-233 symptomatic and 122 asymptomatic of prolapse. The median P-QOL
      domain scores ranged between 42-100 in symptomatic women and 0-25 in those who
      were asymptomatic. The stage of prolapse was significantly higher in those
      symptomatic of prolapse (P < 0.001) except for perineal body (PB) measurement.
      Urinary symptoms were not correlated with uterovaginal prolapse severity whereas
      bowel symptoms were strongly associated with posterior vaginal wall prolapse.
      Cervical descent was found to have a relationship with sexual dysfunction
      symptoms. CONCLUSIONS: Women who present with symptoms specific to pelvic organ
      prolapse demonstrate greater degrees of pelvic relaxation than women who present
      without symptoms. Prolapse severity and quality of life scores are significantly
      different in those women symptomatic of prolapse. There was a stronger
      relationship between posterior prolapse and bowel symptoms than anterior prolapse
      and urinary symptoms. Sexual dysfunction was related to cervical descent.

PMID- 15958003
TI  - Oestradiol and FSH in gestational trophoblastic disease: a prospective analysis
      of their predictive value.
AB  - OBJECTIVE: To determine whether oestradiol or follicle-stimulating hormone (FSH)
      measured prior to treatment could improve the predictive value of the risk score
      used to determine treatment in cases of persistent gestational trophoblastic
      disease (GTD). DESIGN: Prospective observational study. SETTING: Tertiary
      referral centre for GTD. POPULATION: All women referred to Weston Park Hospital,
      Sheffield, with GTD between 1st January 1996 and 31st December 2000. METHODS:
      Blood was taken prior to the initiation of treatment to measure oestradiol and
      FSH. The results were analysed with respect to the time taken for the beta-hCG to
      return to normal. MAIN OUTCOME MEASURES: Time taken to reach a normal beta-hCG.
      RESULTS: Data on 118 women were collected. Three women died of GTD during follow
      up. Using Cox's proportional hazards regression analysis, division of the risk
      scores into high and low risk groups (</=7, >7) demonstrated a significant
      difference with regard to the length of time taken to reach a normal beta-hCG
      level (hazard ratio 0.32; 95% CI: 0.18, 0.57) comparing high risk relative to low
      risk. However, addition of neither oestradiol nor FSH to the Cox regression
      analysis produced a significant hazard ratio (Ln oestradiol, 0.95; FSH 0.99).
      Division of the patients' risk scores into three groups of low (0-4),
      intermediate (5-7) and high (>7) risk groups produced similar results.
      CONCLUSIONS: The measurement of neither oestradiol nor FSH appears to improve the
      prediction of outcome in persistent GTD when added to the risk score.

PMID- 15958004
TI  - DT56a (Femarelle) stimulates bone formation in female rats.
AB  - OBJECTIVE: DT56a is a natural compound for the treatment of menopausal symptoms
      and osteoporosis. The aim of this study was to examine the effects of long term
      treatment (two months) with DT56a on the skeletal tissues of intact and
      ovariectomised (OVX) adult rats. DESIGN: Thirty rats were divided into two
      groups, in one of which the rats were ovariectomised. The rats in each group were
      then treated for two months with DT56a, oestrogen or vehicle. SETTING: University
      and hospital laboratories. POPULATION: Thirty rats. METHODS: Histomorphometric
      measurements of trabecular bone volume (expressed as a percentage of total bone
      volume), trabecular and cortical thickness and growth plate width were recorded
      by a computerised system. In addition, creatine kinase (CK)-specific activity, as
      marker of oestrogen receptor activation, was measured in skeletal tissues and in
      the uterus. MAIN OUTCOME MEASURES: The changes in the histomorphometric
      measurements. RESULTS: OVX rats developed noticeable signs of osteoporosis,
      namely, significant decrease in trabecular bone volume and in trabecular and
      cortical thickness. DT56a, like oestrogen, restored the bone structure
      measurements of all tested parameters in the OVX rats to the values obtained in
      the intact rats. In skeletal tissues, CK activity was elevated in both treatment
      groups. However, in the uterus DT56a did not activate oestrogen receptors while
      oestrogen did elevate CK activity. CONCLUSIONS: DT56a was as effective as
      oestrogen in reversing the bone changes caused by OVX in rats.

PMID- 15958005
TI  - Maternal and perinatal morbidity of caesarean delivery at full cervical
      dilatation compared with caesarean delivery in the first stage of labour.
AB  - To estimate maternal and perinatal morbidity associated with caesarean delivery
      at full cervical dilatation, a population-based cohort study from 1997 to 2002
      was used, which included 1623 nullipara with singleton pregnancies at 37-42 weeks
      of gestation requiring caesarean delivery in labour. Compared to caesarean
      delivery at less than full dilatation, women undergoing caesarean delivery at
      full dilatation were more likely to have complications of intraoperative trauma
      (RR 2.6, P < 0.001) and infants with perinatal asphyxia (RR 1.5, P < 0.05). There
      was no difference in maternal or perinatal morbidity when duration of the second
      stage of labour or when failed assisted vaginal delivery was considered.

PMID- 15958006
TI  - Transvaginal biopsy in the diagnosis of ovarian cancer.
AB  - Laparotomy and debulking surgery followed by chemotherapy have been the treatment
      of choice in late stage ovarian carcinoma. Developments in the chemotherapeutic
      management of ovarian cancer have resulted in a change in opinion as to the
      optimal management of this disease. Many patients are now receiving initial
      chemotherapy and trials are in place to compare up front and adjuvant surgery.
      Tissue diagnosis is required prior to commencing chemotherapy. This article
      describes one method for accurately obtaining a tumour biopsy. A retrospective
      case note review of 14 women with a provisional diagnosis of ovarian carcinoma
      who underwent transvaginal biopsy of their pelvic disease is described. Only 7/12
      cases with a positive biopsy had a definite diagnosis of ovarian cancer. The
      procedure was found to be safe and well tolerated.

PMID- 15958007
TI  - Investigating the relationship between affluence and elective caesarean sections.
AB  - The proportion of women delivering by caesarean section has increased
      dramatically in England and many westernised countries. It has been suggested
      that one important reason for this increase is the growing proportion of women
      opting for elective caesareans for lifestyle reasons, a trend that is, it is
      argued, most common among the affluent. We investigated the hypothesis that
      affluent women are more likely to deliver by elective caesarean section. Logistic
      regression modelling was used to analyse data from half a million women who
      delivered in English NHS hospitals between 1996 and 2000. We found that women
      living in the most affluent areas of England were significantly more likely to
      have an elective caesarean section than their deprived counterparts.

PMID- 15958008
TI  - Shoulder dystocia training using a new birth training mannequin.
AB  - Shoulder dystocia 'skill drills' are a requirement for the Maternity CNST
      standards. However, there is, as yet, no evidence that training in the management
      of shoulder dystocia improves outcome. We developed a mannequin for training and
      investigated its effectiveness. The management of shoulder dystocia improved
      following training with the mannequin. There was a reduction in the head-to-body
      delivery duration, and the maximum applied delivery force, following training;
      however, these did not reach statistical significance. After training no subject
      applied a delivery force of greater than 100 N, a level above which fetal injury
      has been shown to occur.

PMID- 15958009
TI  - Genital myiasis in a woman with psychiatric disturbance.

PMID- 15958010
TI  - Prenatal embolisation of a large chorioangioma using enbucrilate.

PMID- 15958011
TI  - Three consecutive uterine ruptures in the same woman, each with fetal survival.

PMID- 15958013
TI  - Characterization of polymer thin films by phase-sensitive acoustic microscopy and
      atomic force microscopy: a comparative review.
AB  - The potential of phase-sensitive acoustic microscopy (PSAM) for characterizing
      polymer thin films is reviewed in comparison to atomic force microscopy (AFM).
      This comparison is based on results from three-dimensional vector contrast
      imaging and multimodal imaging using PSAM and AFM, respectively. The similarities
      and differences between the information that can be derived from the AFM
      topography and phase images, and the PSAM phase and amplitude micrographs are
      examined. In particular, the significance of the PSAM phase information for
      qualitative and quantitative characterization of the polymer films is examined
      for systems that generate surface waves, and those that do not. The relative
      merits, limitations and outlook of both techniques, individually, and as a
      complementary pair, are discussed.

PMID- 15958014
TI  - Laser pressure catapulting followed by B actin gene identification in Japanese
      quail macrochromosomes and microchromosomes using teflon-coated coverslip slides.
AB  - Laser microdissection of individual mammalian chromosomes (> 2 microm) has been
      achieved though the use of a microscope slide coated with a polyethylene
      naphthalate (PEN) membrane. Although these slides have proved sufficient for
      larger chromosomes, they are insufficient for small chromosomes (< 1 microm). We
      have developed a new type of slide which allows laser microdissection of single
      Japanese quail microchromosomes (0.5 microm) and macrochromosomes (3-4 microm).
      To test the usefulness of these slides, a Japanese quail single nucleus, a
      macrochromosome, and a microchromosome were collected with Laser pressure
      catapulting, the B-actin gene was PCR amplified, and sequenced. The resulting PCR
      product was confirmed by nucleotide sequencing to be B-actin. These newly
      developed slides were shown to facilitate the laser microdissection of both
      Japanese quail macrochromosomes and microchromosomes.

PMID- 15958012
TI  - Sample preparation procedures for biological atomic force microscopy.
AB  - Since the late 1980s, atomic force microscopy (AFM) has been increasingly used in
      biological sciences and it is now established as a versatile tool to address the
      structure, properties and functions of biological specimens. AFM is unique in
      that it provides three-dimensional images of biological structures, including
      biomolecules, lipid films, 2D protein crystals and cells, under physiological
      conditions and with unprecedented resolution. A crucial prerequisite for
      successful, reliable biological AFM is that the samples need to be well attached
      to a solid substrate using appropriate, nondestructive methods. In this review,
      we discuss common techniques for immobilizing biological specimens for AFM
      studies.

PMID- 15958015
TI  - Light microscopic identification and semiquantification of polyethylene particles
      in methylmethacrylate and paraffin-embedded experimental bone implant specimens.
AB  - The aim of this study was to evaluate the identification of polyethylene (PE)
      particles in relatively thick methylmethacrylate (MMA) sections widely used in
      bone implant research. The sensitivity and specificity were compared between
      decalcified paraffin-embedded oil red O (ORO) stained and MMA-embedded sections
      using polarized light. Furthermore, we introduced a grading system to
      semiquantify the level of PE particles in peri-implant tissue. Paraffin-embedded
      and MMA-embedded sections were compared concerning intra-observer agreement of
      the grading system. Moreover, the semiquantitative assessment of particle level
      was compared between the two section types. We found a sensitivity and
      specificity of polarized light of 100% for both paraffin ORO-stained and MMA
      sections. The intra-observer agreement on both types was comparable and
      acceptable. The ratings of differently processed blocks (MMA- and paraffin
      embedded) originating from the same bone implant specimen showed good
      correlation. Our study showed that relatively thick MMA sections were just as
      suitable as ORO-stained paraffin sections concerning peri-implant PE particle
      migration analysis. MMA sections do not allow analysis at cellular level, but
      unbiased estimation of bone ingrowth into the implant surface based on
      stereological principles is possible.

PMID- 15958016
TI  - Immobilization and condensation of DNA with 3-aminopropyltriethoxysilane studied
      by atomic force microscopy.
AB  - We used different methods to modify a mica surface with 3
      aminopropyltriethoxysilane (APTES), and then used it as substrate to immobilize
      DNA for atomic force microscopy (AFM) observation. The evaporation method and
      solution modifying method were investigated and evaluated. The solution modifying
      method was found to be relatively simple and effective. Using an APTES solution
      modified mica surface, DNA immobilization appeared more reproducible and it could
      be imaged in liquid. The mixed solution of APTES and DNA was dropped directly
      onto the mica surface for AFM imaging. We found that DNA can condense in APTES
      water solutions. Toroids, rods and intermediate structures of condensation were
      captured by AFM.

PMID- 15958017
TI  - A simple enzymatic method for examining calcite ossicles of Echinodermata.
AB  - The various shapes, size and fine details of ossicles are of paramount importance
      as systematic characters in the Echinodermata. The ossicles in this group are
      endodermal and a method to free them from the dermis is essential for their
      study. To date, a small quantity of hypochlorite solution (usually household
      liquid bleach) has been used to dissolve a small piece of tissue and,
      consequently, free these ossicles. A new method, using a proteolytic enzyme
      instead of hypochlorite solution to dissolve holothurian tissues, is proposed.
      This method was tested on fragments of body tissues from three species in three
      different orders of holothurians: Holothuria grisea Selenka, 1867
      (Aspidochirotida), Duasmodactyla seguroensis (Deichmann, 1930) (Dendrochirotida)
      and Synaptula secreta Ancona Lopez (1957) (Apodida). Observations of material
      prepared using the hypochlorite and the enzyme methods were made using scanning
      electron microscopy (SEM). The SEM images show the striking differences in the
      surface of the ossicles obtained by each method, and reveal the advantages of the
      enzyme method.

PMID- 15958018
TI  - Image analysis of X-ray microtomograms of soft materials during convective
      drying: 3D measurements.
AB  - Drying dewatered sludge leads to a complex three-dimensional porous structure.
      Moreover, this operation is dependent on the way the material is processed. In
      this study, textural changes of sludge extrudates submitted to convective drying
      are followed by a 3D image analysis of reconstructed X-ray microtomograms. To
      achieve this goal, two different wastewater sludges collected in wastewater
      treatment plant after the thickening step and dewatered in the laboratory are
      used. It is showed that the evolution of the 3D-crack ratio vs. the residual
      water content evolves following a hyperbolic law. The 3D opening crack size
      distribution reveals two different types of pore development, i.e. a continuous
      pore size evolution for one sludge and the sudden appearance of cracks for the
      other sludge.

PMID- 15958019
TI  - Fluorescence resonance energy transfer (FRET) measurement by gradual acceptor
      photobleaching.
AB  - Fluorescence resonance energy transfer (FRET) is an extremely effective tool to
      detect molecular interaction at suboptical resolutions. One of the techniques for
      measuring FRET is acceptor photobleaching: the increase in donor fluorescence
      after complete acceptor photobleaching is a measure of the FRET efficiency.
      However, in wide-field microscopy, complete acceptor photobleaching is difficult
      due to the low excitation intensities. In addition, the method is sensitive to
      inadvertent donor bleaching, autofluorescence and bleed-through of excitation
      light. In the method introduced in this paper, donor and acceptor intensities are
      monitored continuously during acceptor photobleaching. Subsequently, curve
      fitting is used to determine the FRET efficiency. The method was demonstrated on
      cameleon (YC2.1), a FRET-based Ca(2+) indicator, and on a CFP-YFP fusion protein
      expressed in HeLa cells. FRET efficiency of cameleon in the presence of 1 mm
      Ca(2+) was 31 +/- 3%. In the absence of Ca(2+) a FRET efficiency of 15 +/- 2% was
      found. A FRET efficiency of 28% was found for the CFP-YFP fusion protein in HeLa
      cells. Advantages of the method are that it does not require complete acceptor
      photobleaching, it includes correction for spectral cross-talk, donor
      photobleaching and autofluorescence, and is relatively simple to use on a normal
      wide-field microscope.

PMID- 15958020
TI  - Mosquito vectors of the 1998-1999 outbreak of Rift Valley Fever and other
      arboviruses (Bagaza, Sanar, Wesselsbron and West Nile) in Mauritania and Senegal.
AB  - Following an outbreak of Rift Valley fever (RVF) in south-eastern Mauritania
      during 1998, entomological investigations were conducted for 2 years in the
      affected parts of Senegal and Mauritania, spanning the Senegal River basin. A
      total of 92 787 mosquitoes (Diptera: Culicidae), belonging to 10 genera and 41
      species, were captured in light traps. In Senegal, Culex poicilipes (41%) and
      Mansonia uniformis (39%) were the most abundant species caught, whereas Aedes
      vexans (77%) and Cx. poicilipes (15%) predominated in Mauritania. RVF virus was
      isolated from 63 pools of Cx. poicilipes: 36 from Senegal in 1998 and 27 from
      Mauritania in 1999. These results are the first field evidence of Cx. poicilipes
      naturally infected with RVFV, and the first isolations of this virus from
      mosquitoes in Mauritania - the main West African epidemic and epizootic area.
      Additional arbovirus isolates comprised 25 strains of Bagaza (BAG) from Aedes
      fowleri, Culex neavei and Cx. poicilipes; 67 Sanar (ArD 66707) from Cx.
      poicilipes; 51 Wesselsbron (WSL) from Ae. vexans and 30 strains of West Nile (WN)
      from Ma. uniformis, showing differential specific virus-vector associations in
      the circulation activity of these five arboviruses.

PMID- 15958021
TI  - Expression, production and excretion of Bla g 1, a major human allergen, in
      relation to food intake in the German cockroach, Blattella germanica.
AB  - The German cockroach, Blattella germanica (Linnaeus) (Dictyoptera: Blattellidae),
      produces several potent human allergens, one of which, Blattella germanica
      allergen 1 (Bla g 1), is produced in the midgut and excreted in faeces. We tested
      with descriptive and experimental approaches the hypothesis that Bla g 1
      production is related to food intake in adult males and females of the German
      cockroach. Bla g 1 mRNA expression in the female midgut (assayed by real time
      quantitative polymerase chain reaction), her Bla g 1 content (assayed by enzyme
      linked immunosorbent assay), and the female's faeces production and its Bla g 1
      content tracked a cyclic pattern in relation to the gonadotrophic cycle. All four
      measures rose as food intake increased, declined before oviposition in relation
      to diminishing food intake, and remained low while the female carried an egg case
      for 20 days. After her first clutch of embryos hatched, the female resumed
      feeding, and faeces and Bla g 1 production increased concomitantly. Both Bla g 1
      mRNA expression and Bla g 1 protein levels remained low in experimentally starved
      females. However, when starved females were allowed to feed, Bla g 1 production
      elevated and the gonadotrophic cycle resumed. Bla g 1 mRNA expression also
      increased six-fold in response to feeding compared to starved females. By
      contrast, there were no apparent cycles in the pattern of Bla g 1 production in
      males, reflecting their low and non-cyclic food intake. Our results therefore
      demonstrate that Bla g 1 production in B. germanica is modulated in relation to
      food intake.

PMID- 15958022
TI  - Musca domestica is not a vector of Thelazia callipaeda in experimental or natural
      conditions.
AB  - Thelazia callipaeda Railliet and Henry (Spirurida: Thelaziidae), commonly called
      oriental eyeworm for its widespread presence in the Far East, has been recently
      found to affect dogs, cats and foxes in northern and southern Italy. Although the
      biology of T. callipaeda in the definitive hosts has been recently investigated,
      many doubts still remain about its biology in insect vectors. It has been
      suggested that more than one species of Diptera, namely Musca domestica Linnaeus
      (Diptera: Muscidae) and Amiota okadai Maca (Diptera: Drosophilidae), may be
      involved in the transmission of T. callipaeda in China. The aim of the work
      described here was to verify the role of M. domestica as a vector of T.
      callipaeda both in experimental and natural conditions. A total of 310 m.
      domestica (Group 1) were put in a cage and allowed to feed for 14 days around the
      eyes of a dog naturally infected by T. callipaeda. Ten flies were collected daily
      for 14 days. A total of 149 houseflies (Group 2) were fed with T. callipaeda
      first stage larvae (L1) and dissected at 1, 2 and 7 days post-infection. From
      June to August 2003, flies were netted (Group 3) in two different sites every 10
      days both from the environment and directly from the periocular region of dogs
      affected by thelaziosis. Musca flies were examined for eyeworms by dissection and
      visual inspection of house flies (Groups 1 and 2) and using a molecular approach
      (Groups 1-3) via a specific amplification of the ribosomal internal transcribed
      spacer 1 (ITS1) sequence of T. callipaeda. On the whole, 180 pools of M.
      domestica flies were processed molecularly and all the experimentally infected
      flies (Groups 1 and 2) were found to be negative both at the visual dissection
      and at the molecular assay. Similarly, the 234 M. domestica collected from Group
      3 were negative for T. callipaeda. The results clearly suggest that M. domestica
      is unlikely to act as a vector of T. callipaeda in southern Europe, in contrast
      with a single previous report.

PMID- 15958023
TI  - Seasonality of Old World screwworm myiasis in the Mesopotamia valley in Iraq.
AB  - Following the first recorded introduction of the Old World screwworm fly (OWS),
      Chrysomya bezziana Villeneuve (Diptera: Calliphoridae), into the Mesopotamia
      valley in Iraq in September 1996, cases of livestock myiasis caused by OWS
      developed a distinctly seasonal pattern. The annual cycle of clinical OWS cases
      is explained here on the basis of environmental variables that affect the
      different life-cycle stages of C. bezziana. This analysis suggests that low
      temperatures restricted pupal development during the winter, whereas the
      dispersal of adult flies was constrained by hot/dry summer conditions. A
      restricted number of OWS foci persisted throughout the year. In these foci, pupal
      development was fastest during the autumn months. In autumn, rapid
      multiplication, lasting several OWS generations, allowed subsequent adult fly
      dispersal across the valley floor during the winter. Hence, the monthly incidence
      of clinical OWS cases in livestock peaked during December-January and was lowest
      during July-August. In addition to temperature and humidity, vegetation cover
      played a role in OWS distribution. Hence the majority of OWS cases were clustered
      in the medium density type of vegetation [normalized difference vegetation index
      (NDVI) values of 0.2-0.4] along the main watercourses in the marshy Mesopotamia
      valley. Although sheep were the host most commonly infested by C. bezziana, local
      sheep density was not found to be a major factor in disease spread. Satellite
      imagery and the application of Geographical Information System (GIS) tools were
      found to be valuable in understanding the distribution of OWS in relation to
      vegetation and watercourses. The presence of screwworm in Iraq, at the perimeter
      of the intercontinental OWS distribution, may give rise to major seasonal flare
      ups.

PMID- 15958024
TI  - Analysis of larval antigens of Oestrus ovis for the diagnosis of oestrosis by
      enzyme-linked immunosorbent assay.
AB  - A serodiagnostic test for the diagnosis of infestation by the sheep nasal bot
      fly, Oestrus ovis (Linne) was examined. The enzyme-linked immunosorbent assay
      (ELISA) technique was used to analyze and compare the production of
      immunoglobulin G (IgG) antibodies against excretory-secretory products (ESP) and
      crude extract (CE) antigens from all the different larval stages of O. ovis in
      the sera of 276 adult sheep sampled in summer (n = 135) and winter (n = 141). ESP
      from first stage larvae was the most sensitive, coating antigen in winter and ESP
      from second stage larvae during summer. The most specific values were obtained by
      ESP against L1 in winter and by CE against L3 in summer. These results show that
      the stage of larval development has a significant impact on the humoral immune
      response over the course of a season. A significant correlation (P < 0.001) was
      found between the number of O. ovis larvae and the serum antibody levels using
      all differents antigens, except L3 CE. In Spain, where a long favourable period
      exists for the evolution and development of the different stage larvae between
      March and November, the ELISA test using L1 ESP antigen during winter and L2 ESP
      antigen in summer may be used for ovine oestrosis immunodiagnosis.

PMID- 15958025
TI  - Six new species of the Anopheles leucosphyrus group, reinterpretation of An.
      elegans and vector implications.
AB  - Among Oriental anopheline mosquitoes (Diptera: Culicidae), several major vectors
      of forest malaria belong to the group of Anopheles (Cellia) leucosphyrus Donitz.
      We have morphologically examined representative material (> 8000 specimens from
      seven countries) for taxonomic revision of the Leucosphyrus Group. Six new
      species are here described from adult, pupal and larval stages (with
      illustrations of immature stages) and formally named as follows: An. latens n.
      sp. (= An. leucosphyrus species A of Baimai et al., 1988b), An. cracens n. sp.,
      An. scanloni n. sp., An. baimaii n. sp. (formerly An. dirus species B, C, D,
      respectively), An. mirans n. sp. and An. recens n. sp. Additionally, An. elegans
      (James) is redescribed and placed in the complex of An. dirus Peyton & Harrison
      (comprising An. baimaii, An. cracens, An. dirus, An. elegans, An. nemophilous
      Peyton and Ramalingam, An. scanloni and An. takasagoensis Morishita) of the
      Leucosphyrus Subgroup, together with An. baisasi Colless and the An. leucosphyrus
      complex (comprising An. balabacensis Baisas, An. introlatus Baisas, An. latens
      and An. leucosphyrus). Hence, the former Elegans Subgroup is renamed the Hackeri
      Subgroup (comprising An. hackeri Edwards, An. pujutensis Colless, An. recens and
      An. sulawesi Waktoedi). Distribution data and bionomics of the newly defined
      species are given, based on new material and published records, with discussion
      of morphological characters for species distinction and implications for ecology
      and vector roles of such species. Now these and other members of the Leucosphyrus
      Group are identifiable, it should be possible to clarify the medical importance
      and distribution of each species. Those already regarded as vectors of human
      malaria are: An. baimaii[Bangladesh, China (Yunnan), India (Andamans, Assam,
      Meghalaya, West Bengal), Myanmar, Thailand]; An. latens[Borneo (where it also
      transmits Bancroftian filariasis), peninsular Malaysia, Thailand]; probably An.
      cracens (Sumatra, peninsular Malaysia, Thailand); presumably An. scanloni
      (Thailand); perhaps An. elegans (the Western Ghat form of An. dirus, restricted
      to peninsular India); but apparently not An. recens (Sumatra) nor An. mirans[Sri
      Lanka and south-west India (Karnataka, Kerala, Tamil Nadu)], which is a natural
      vector of simian malarias. Together with typical An. balabacensis, An. dirus and
      An. leucosphyrus, therefore, the Leucosphyrus Group includes about seven
      important vectors of forest malaria, plus at least a dozen species of no known
      medical importance, with differential specific distributions collectively
      spanning > 5000 km from India to the Philippines.

PMID- 15958026
TI  - A comparison of the susceptibility of Culicoides imicola and C. bolitinos to oral
      infection with eight serotypes of epizootic haemorrhagic disease virus.
AB  - The mechanisms involved in introduction, maintenance and perpetuation of
      epizootic haemorrhagic disease virus (EHDV) in South Africa are not fully
      understood. This paper reports on the susceptibility of South African livestock
      associated Culicoides (Diptera: Ceratopogonidae) species to oral infection with
      eight EHDV serotypes. Virus was recovered from eight of 17 field-collected
      Culicoides species 10 days after oral feeding on blood/virus mixtures. Six EHDV
      serotypes were recovered from C. (Avaritia) imicola Kieffer, and seven serotypes
      were recovered from C. (A.) bolitinos Meiswinkel. Virus recovery rates in C.
      imicola ranged from 0.4% for EHDV 2 to 14.4% for EHDV 7, and in C. bolitinos from
      0.6% for EHDV 6 to 12.3% for EHDV 2. There was a significant difference in virus
      recovery rates between serotypes in both species. Other Culicoides species that
      yielded EHDV after 10 days extrinsic incubation included C. (Meijerehelea)
      leucostictus Kieffer, C. (Culicoides) magnus Colaco, C. (Beltranmyia) nivosus de
      Meillon, C. (A.) gulbenkiani Caeiro, C. (Hoffmania) zuluensis de Meillon and C.
      onderstepoortensis Fiedler. Culicoides midges shown in this study to be
      susceptible to oral infection with EHDV are widely distributed in South Africa
      but differ considerably in their abundance, host preference and breeding sites.

PMID- 15958027
TI  - Amazonian malaria vector anopheline relationships interpreted from ITS2 rDNA
      sequences.
AB  - Species identification of anopheline mosquitoes (Diptera: Culicidae) can be
      problematic because many of them belong to complexes of morphologically similar
      species, often with contrasted ecology, behaviour and vectorial importance. The
      application of DNA-based diagnostics has proved to be useful for distinguishing
      between such species. We determined ribosomal DNA sequences of the second
      internal transcribed spacer (ITS2) from samples of 16 species of Anopheles
      captured in the Amazon Basin, Brazil. Length of the ITS2 varied from 323 to 410
      base pairs, with GC content ranging from 50.7% to 66.5% and sequence identity
      from 25% to 99% between species. Maximum-likelihood paup analysis separated two
      distinct groups of species conforming with the recognized subgenera Anopheles
      (represented by eiseni, mattogrossensis, mediopunctatus and peryassui) and
      Nyssorhynchus (represented by 12 spp.). For the latter group, the neighbour
      joining tree generated from rDNA sequence ITS2 relationships is compatible with
      the morphological taxonomic key established for these Amazonian species:
      albitarsis, aquasalis, benarrochi, braziliensis, darlingi, deaneorum, dunhami,
      evansae, nuneztovari, oswaldoi, rangeli and triannulatus. These ITS2 sequence
      data proved to be a useful tool for species identification and, potentially, to
      solve taxonomic problems.

PMID- 15958028
TI  - Risk factors associated with house infestation by the Chagas disease vector
      Triatoma pallidipennis in Cuernavaca metropolitan area, Mexico.
AB  - Chagas disease caused by infection with Trypanosoma cruzi Chagas (Kinetoplastida:
      Trypanosomatidae) is widespread in Mexico, transmitted by various triatomine bugs
      (Hemiptera: Reduviidae). The only domestic vector in Cuernavaca (population 650
      000) is Triatoma pallidipennis (Stahl) with T. cruzi seroprevalence ranging from
      1% to 9% in the resident human population. We surveyed possible risk factors for
      T. pallidipennis infestation at Cuernavaca (altitude 1200-2200 m) on south
      western slopes of the Sierra Madre Occidental. This metropolitan area (with five
      administrative counties) has rapid urbanization, forested environs and
      proliferation of 'weekend housing' for visitors from Mexico City, 60 km to the
      north. To assess factors associated with T. pallidipennis infestation, we first
      stratified Cuernavaca by altitude and by socio-economic status of population
      catchment units (PCUs). Within each PCU, one to three blocks were chosen for
      cluster sampling (three houses/block) and information about Chagas disease was
      distributed. After obtaining signed consent from householders, representative
      houses were routinely and opportunistically inspected for T. pallidipennis and
      surveyed for demographic, economic, physical and other potential risk factors. Of
      the 1129 houses assessed, T. pallidipennis was found in 4.1% (range 3.0-6.8% per
      county) and the T. cruzi infection rate was approximately 50% in bugs. Rates of
      house infestation in poor PCUs were double those in higher socio-economic strata
      (odds ratio 2.12, confidence interval 1.03-4.3), with >4-fold greater crowding
      index of T. pallidipennis. The bug density index was inversely correlated with
      PCU altitude and socio-economic category (altitude of homes being associated with
      prosperity), while the bug colonization index (presence of nymphs indicating
      breeding) did not vary significantly across the PCU categories, but did vary
      according to altitude. Multivariate regression analysis showed that the most
      significant risk factors associated with T. pallidipennis infestation were lower
      altitude (linked with lower socio-economic status), garden area >80 m(2), dogs at
      liberty to enter the house, occurrence of squirrels and opossums around the
      house, presence of pigs in the surrounding area and having at least one of the
      adjacent lots empty (unconstructed). Householders who had received information
      about Chagas disease comprised 33% from infested houses (14/42) but only 15% from
      non-infested houses (148/984). Hence, the awareness of Chagas disease was
      significantly associated with having a bug-free house (P < 0.01). When shown
      specimens of T. pallidipennis, the proportions of householders who recognized
      them were 78% from infested houses but only 29% of those with uninfested houses.
      Given the low infestation rates and the high capacity of the population to act
      appropriately once they have received information regarding this disease and its
      vector, relevant health education is expected to have a significant impact on
      triatomine control in this metropolitan area.

PMID- 15958029
TI  - Duration of development of two species of carrion-breeding scuttle flies and
      forensic implications.
AB  - A procedure for rearing carrion-breeding scuttle flies (Diptera: Phoridae) under
      naturally fluctuating temperatures is described. Data on the duration of
      development of the egg stage, egg plus feeding larval stages, postfeeding larvae
      and total development from egg to adult, at different temperature regimes (means
      of daily means) are tabulated for Megaselia giraudii (Egger) and M. rufipes
      (Meigen). The variation is greater than previously supposed and involves larvae
      derived from the same egg batch leaving the bait in successive waves. Despite
      this variation the tables allow the provision of percentage probabilities of
      estimations of the earliest oviposition dates for specimens collected from a
      forensic case.

PMID- 15958031
TI  - Home haemodialysis: 'home, home, sweet, sweet home!'.
AB  - Home haemodialysis was first developed 40 years ago as a means of treating more
      patients with the limited funds then available. It soon became obvious that the
      treatment worked well and subsequent studies and experience have confirmed that
      it improves both mortality and morbidity and provides the best quality of life
      and other benefits for dialysis patients. The present review describes the
      history of the development of home haemodialysis in Seattle and elsewhere and the
      lessons learned about its benefits in the early days, which are just as relevant
      today. The advantages and disadvantages are discussed, as are the issues of which
      patients are candidates for this treatment and what is required of a home
      haemodialysis training and support programme. The decline in use of home
      haemodialysis in the USA and elsewhere is described and the actions that may
      already be beginning to reverse this trend. The role of home haemodialysis in
      giving the opportunity for longer hours of dialysis three times a week or on
      alternate nights is important. There is discussion of the relationship of home
      haemodialysis and peritoneal dialysis and its important future role as the means
      to enable treatment with more frequent short daily and long nightly
      haemodialysis.

PMID- 15958032
TI  - History of home haemodialysis in Australia.
AB  - Australia has had an active and slowly expanding home haemodialysis programme;
      however, this has failed to expand as rapidly as some other methods of treatment
      of end-stage kidney disease. The technique in Australia has always been a
      derivative from overseas experience, rather than innovative. It received some
      minor initial support from the report issued in 1968 by an ad-hoc Committee of
      the National Health and Medical Research Council on Rationalization of Facilities
      for Organ Transplantation and Renal Dialysis, but was ultimately disadvantaged
      because the report promoted transplantation over dialysis to an extent that
      proved markedly disproportionate to the number of patients who, in succeeding
      decades, would need maintenance dialysis treatment rather than transplantation.
      Nevertheless, each state in Australia established home haemodialysis facilities,
      but major interstate variations occurred in the uptake of the modality. The
      subsequent development of continuous ambulatory peritoneal dialysis and limited
      care dialysis centres appeared to have an important negative impact on home
      haemodialysis, although the recent introduction of daily dialysis is likely to
      have a positive influence in the future.

PMID- 15958033
TI  - Nocturnal haemodialysis in Australia and New Zealand.
AB  - Although early experience in Australia and New Zealand confirmed home
      haemodialysis to be well tolerated, effective and with lower morbidity and
      mortality compared with centre-based haemodialysis, the advent of ambulatory
      peritoneal dialysis and 'satellite' haemodialysis has led to a steadily declining
      home haemodialysis population. However, the emergence of nocturnal haemodialysis,
      as a safe and highly effective therapy, has added to the modality choices now
      available and offers a new, highly attractive home-based option with many
      advantages over centre-based dialysis. For the patient, nocturnal haemodialysis
      means fluid and dietary freedom, less antihypertensive medication, the abolition
      of phosphate binders, the return of daytime freedom and the capacity for full
      time employment. Potential biochemical benefits include normalization of the
      blood urea, serum creatinine, albumin, beta(2) microglobulin, homocysteine and
      triglyceride levels and other nutritional markers. Improved quality of life and
      sleep patterns and a resolution of sleep apnoea have been shown. Left ventricular
      function has also shown marked improvement. For the provider, nocturnal home
      haemodialysis offers clear cost advantages by avoiding high-cost nursing and
      infrastructure expenditure. Although consumable and equipment costs are higher,
      the savings on wage and infrastructure far outweigh this added expenditure. These
      combined factors make nocturnal haemodialysis an irresistible addition to
      comprehensive dialysis services, both from a clinical outcome and fiscal
      perspective.

PMID- 15958034
TI  - Future of home haemodialysis in Australia and New Zealand.
AB  - Maintenance haemodialysis (HD) was pioneered in Seattle and rapidly became home
      based. When dialysis treatment began in Australia and New Zealand, home
      haemodialysis (HHD) became the predominant form of dialysis. When compared with
      in-centre conventional dialysis, HHD is associated with superior survival and
      quality of life and is cheaper. There is currently significant interest in
      increasing the frequency and duration of dialysis and in providing more flexible
      dialysis regimens for patients. If the likely benefits of these treatment changes
      are to be fully realized HHD and self care HD services will need to expand.
      Dialysis units in Australia and New Zealand are better equipped than most to
      respond to this challenge.

PMID- 15958035
TI  - Bad and good growth factors in the peritoneal cavity.
AB  - Progressive peritoneal membrane fibrosis, and associated loss of ultrafiltration
      and dialysis capacity, is an increasingly limiting problem with time on
      peritoneal dialysis. The primary culprit is the composition of the peritoneal
      dialysate, although episodes of peritonitis can hasten the process. At a
      molecular level, there is increasing evidence that several growth factors play
      key roles in the development of peritoneal membrane fibrosis. Transforming growth
      factor (TGF)-beta is widely implicated in pathological fibrosis, and a
      considerable body of evidence favours a similar role in the peritoneal membrane.
      Connective tissue growth factor (CTGF), a downstream mediator of TGF-beta-induced
      fibrosis, has more recently been implicated in peritoneal membrane scarring. In
      contrast to the pleiotropic effects of TGF-beta, CTGF more specifically targets
      the fibrosis pathway, and so is an attractive candidate for inhibiting the damage
      to the membrane. Heparin-binding epidermal growth factor-like growth factor (HB
      EGF) has also been found in the peritoneal cavity, but its effect on peritoneal
      mesothelial cells suggests that it has a positive role in guiding membrane repair
      and avoiding pathological fibrosis. In the future, it is hoped that changes in
      peritoneal dialysis technology will create a better balance between the bad and
      good effects of these growth factors, which in turn will lead to more successful
      long-term outcomes for this major renal replacement therapy.

PMID- 15958036
TI  - Prevention of catheter-related bloodstream infections: an appraisal of
      developments in designing an infection-resistant 'dream dialysis-catheter'.
AB  - With the increasing number of elderly, diabetics and debilitated patients being
      accepted for haemodialysis (HD), the use of central venous catheters (CVCs) as
      vascular access has become more widespread, with an inevitable inherent risk of
      catheter-related bloodstream infections (CRBSI) and ensuing mortality. No
      reliable plans for the effective management of CRBSI without actually sacrificing
      vascular access sites are presently available. Therefore, the onus really falls
      on renal physicians to make effective use of the established supportive guiding
      principles, practices, policies and programs to prevent CRBSI among HD patients.
      A huge body of research in polymer industry has aimed at alterations of physical,
      chemical, biological and immunological properties of CVCs to prevent the
      bacterial colonization of catheters. Developing an infection-resistant dialysis
      catheter has been an elusive dream. This article analyses the current state-of
      the-art strategies aimed at preventing CRBSI and also reviews the progress made
      to date, in the direction of development of a 'bioactive' thrombosis and
      infection-resistant dialysis catheter.

PMID- 15958037
TI  - Encapsulating peritoneal sclerosis.
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 be from
      0.7% to 7.3%, and the rate appears to be higher in patients receiving long-term
      treatment. Most data from Japan has shown an overall incidence of 2.5% with an
      evident negative effect of increasing duration of PD, which also augments
      mortality. Since EPS occurred after withdrawal from PD in more than half of the
      patients, strict monitoring is necessary when a long-term PD 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 development of
      EPS. Appropriate treatment according to the disease stage is most important in
      EPS treatment. Therefore, when examining a PD patient complaining of
      gastrointestinal symptoms, the possibility of EPS has to be kept in mind. Basic
      therapeutic tactics for EPS include appropriate use of steroids. If the state of
      bowel obstruction persists, laparotomy and enterolysis should be performed to
      obtain a complete cure. It is now recognized that EPS is not a fatal complication
      of PD.

PMID- 15958038
TI  - Serum and peripheral blood mononuclear cells infectious burden: correlation to
      inflammation and atherosclerosis in haemodialysis patients.
AB  - BACKGROUND: Infectious agents may be implicated in the inflammatory
      atherosclerotic process. Not only specific microorganisms but also the infectious
      burden, defined as the number of pathogens to which a patient is exposed, has
      been associated with atherosclerosis. In the present study, the infectious
      burden, determined directly (by identification of viable pathogens in peripheral
      blood mononuclear cells (PBMC)) and indirectly (by serum antibodies detection) is
      correlated to the inflammatory and atherosclerotic status in haemodialysis (HD)
      patients, a population at high risk for cardiovascular disease. METHODS: The
      viable forms of four microorganisms (Chlamydia pneumoniae, herpes virus 1 and 2
      and cytomegalovirus) were identified in patients PBMC by cell cultures and
      subsequent polymerase chain reaction. Serum IgG against the above pathogens and
      Helicobacter pylori were also determined. Inflammation was assessed by
      measurement of C-reactive protein (CRP), serum amyloid A (SAA), three pro- and
      one anti-inflammatory cytokines and four adhesion molecules. Atherosclerosis was
      defined by a scoring system using medical history data. RESULTS: The number of
      viable pathogens identified in PBMC in the 122 HD patients included in the study
      were zero in 22.1% of them, one in 33.6%, two in 43.4% and three in one patient.
      The number of IgG antibodies determined was one in 6.6% of patients, two in 32%,
      three in 48.4% and four in 13.1%. Seropositivity was not significantly different
      between patients with or without the respective viable pathogen identified in
      PBMC. Atherosclerosis was present in 40.2% of patients, and CRP, SAA and
      interleukin-6 were all increased in these patients. Neither inflammatory indexes
      nor atherosclerosis were significantly different in patients with a higher number
      of viable pathogens detected in PBMC or in those with a higher antibodies number.
      CONCLUSIONS: The direct infectious burden determination (the number of viable
      pathogens in PBMC) does not coincide with the serum (by IgG detection) infectious
      burden. Although inflammation correlates to atherosclerosis, neither PBMC nor the
      serum infectious burden is associated with these two entities in the inflamed and
      atherosclerotic HD patients.

PMID- 15958039
TI  - Impact of rHuEPO therapy initiation on soluble adhesion molecule levels in
      haemodialysis patients.
AB  - BACKGROUND: Increased levels of soluble adhesion molecules have been reported in
      haemodialysis (HD) patients. Recent studies have shown that recombinant human
      erythropoietin (rHuEPO) elicits proliferation and migration of endothelial cells
      and modifies endothelial function. The present study was design to explore the
      effects of rHuEPO on serum levels of soluble adhesion molecules in HD patients.
      METHODS: Soluble serum levels of E-selectin (sE-selectin), intracellular adhesion
      molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) were
      measured by ELISA in 29 rHuEPO naive HD patients (20 males, 9 females) and 10
      control subjects at baseline and second month. The HD patients with a haemoglobin
      level lower than 10.0 mg/dL (n = 19) were administered rHuEPO therapy and other
      HD patients (n = 10) were followed as a placebo group. RESULTS: Serum levels of
      soluble adhesion molecules were significantly higher in HD patients compared with
      the control group. A significant rise from the baseline in sE-selectin levels (77
      +/- 70 vs 100 +/- 86 ng/mL, P < 0.05) was observed 2 months after rHuEPO
      initiation, while sICAM-1 and sVCAM-1 levels decreased (271 +/- 261 vs 197 +/- 89
      and 1043 +/- 243 vs 990 +/- 236 ng/mL, respectively, P < 0.05). CONCLUSIONS: The
      present data indicate that rHuEPO could have an important action on serum levels
      of soluble adhesion molecules in HD patients. rHuEPO might modify the expression
      of adhesion molecules from endothelial cells either. However, the exact mechanism
      responsible for the serum elevation of these molecules in HD patients is yet to
      be fully elucidated.

PMID- 15958040
TI  - Aspergillus fumigatus peritonitis in ambulatory peritoneal dialysis: a case
      report and notes on the therapeutic approach.
AB  - Aspergillus peritonitis is a rare disease in continuous peritoneal dialysis. It
      is a severe form of peritonitis, which is frequently lethal. We report a case of
      Aspergillus fumigatus peritonitis in a female patient on automated peritoneal
      dialysis (APD), who was successfully treated with intravenous amphotericin B and
      the removal of the peritoneal catheter. As delayed treatment has an increased
      mortality rate, it is mandatory to remove the catheter and to start intravenous
      treatment with amphotericin B empirically.

PMID- 15958041
TI  - Taste disorders present in patients with chronic renal failure do not have an
      effect on overhydration and excessive weight gain between dialyses.

PMID- 15958042
TI  - Adult stem cells in renal injury and repair.
AB  - There has been considerable focus on the ability of bone marrow-derived cells to
      differentiate into non-haematopoietic cells of various tissue lineages, including
      cells of the kidney. This growing evidence has led to a reconsideration of the
      source of cells contributing to renal repair following injury. The kidney has an
      inherent ability for recovery and regeneration following acute damage. It is
      thought that dedifferentiation of glomerular and tubular cells to a more
      embryonic/mesenchymal phenotype represent key processes for recovery in response
      to damage. However, there has been much contention as to the source of
      regenerating renal cells. The present review focuses on new aspects of the
      plasticity of intrinsic renal cells and their role in renal remodelling and
      scarring. Growing support also suggests that bone marrow-derived cells have the
      ability to contribute to structural and functional repair following acute renal
      failure. Evidence for bone marrow cell engraftment in the repairing kidney
      leading to incorporation into a variety of tissue types is discussed. Because
      cell death and fibrosis is a common end-point in a variety of acute and chronic
      renal nephropathies, the paradigm of stem cell plasticity may have important
      implications in the cellular and pathological mechanisms of renal injury and
      repair. A better understanding of the processes controlling extra-renal cell
      engraftment and intrinsic renal cell differentiation may provide important clues
      for the development of new cell-based therapies in the field of renal reparative
      medicine.

PMID- 15958043
TI  - Prospects for urinary proteomics: exosomes as a source of urinary biomarkers.
AB  - Recent progress in biotechnology offers the promise of better medical care at
      lower costs. Among the techniques that show the greatest promise is mass
      spectrometry of proteins, which can identify proteins present in body fluids and
      tissue specimens at a large scale. Because urine can be collected in large
      amounts in a non-invasive fashion, the potential exists to use mass spectrometry
      to discover urinary biomarkers that are early predictors of renal disease, or
      useful in making therapeutic choices. Recently, the authors demonstrated that
      both membrane proteins and cytosolic proteins from renal epithelia are highly
      enriched in low-density urinary structures identified as exosomes. Exosomes were
      found to contain many disease-associated proteins including aquaporin-2,
      polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na+
      K+ 2Cl- cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and
      epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be
      discovered by mass spectrometry-based proteomic studies in well-defined patient
      populations. Herein is described the advantages of using urinary exosomes as a
      starting material for biomarker discovery. In addition, the purpose of this
      review is to present an overall strategy for biomarker discovery in urine using
      exosomes and for developing cost-effective clinical assays for these biomarkers,
      which can potentially be used for early detection of disease, as a means of
      differential diagnosis, or as a means of guiding therapy. Finally, potential
      barriers that need to be overcome before urinary proteomics can be applied
      clinically, are emphasized.

PMID- 15958044
TI  - Diabetic end-stage renal disease in the indigenous population of the Commonwealth
      of the Northern Mariana Islands.
AB  - The number of cases of treated end-stage renal disease (ESRD) attributable to
      type 2 diabetes and survival after the onset of renal replacement therapy was
      examined in the Commonwealth of the Northern Mariana Islands (CNMI). All
      Chamorros and Carolinians to receive renal replacement therapy for ESRD between
      January 1982 and December 2002 were identified. Changes in survival over time
      were examined by dividing the study into three equal periods. Of 180 new cases of
      ESRD, 137 (76%; 101 Chamorros, 36 Carolinians) were attributed to diabetes.
      Ninety-nine subjects, 80% of whom had diabetic ESRD, began renal replacement
      therapy in the last 7 years of the study compared with 81 (72% with diabetic
      ESRD) in the previous 14 years. All 137 of the diabetic subjects received
      haemodialysis. During the 21-year study period, 79 of the diabetic subjects
      receiving dialysis died. The median survival after the onset of haemodialysis was
      37 months in the first time period (1982-1988), 47 months in the second period
      (1989-1995) and 67 months in the third period (1996-2002). The death rate in the
      first period was 4.3 times (95% CI, 2.1-8.9) as high and the second period was
      2.9 times (95% CI, 1.5-5.8) as high as the most recent period, after adjustment
      for age, sex and ethnicity in a proportional-hazards analysis. The number of
      diabetic patients in CNMI who are receiving renal replacement therapy is rising
      rapidly. Considerable improvement in survival after the onset of haemodialysis
      has occurred over the past 21 years.

PMID- 15958045
TI  - Unmasking the secrets of glomerular disease for diagnosis.

PMID- 15958046
TI  - Immunohistochemical detection of immunoglobulins and complements in formaldehyde
      fixed and paraffin-embedded renal biopsy tissues; an adjunct for diagnosis of
      glomerulonephritis.
AB  - BACKGROUND: The present study was undertaken to demonstrate the deposition of
      immunoglobulins or complements in formaldehyde-fixed and paraffin-embedded renal
      biopsy tissues through the unmasking of antigens with microwave treatment plus
      protease digestion or trypsin digestion. METHODS: Biopsy samples from patients
      with IgA nephritis (n = 7), lupus nephritis (7), membranous nephropathy (7) and
      mesangiocapillary glomerulonephritis (3) were used. Antigen unmasking was
      performed with (i) microwave treatment plus protease digestion for 10, 30 or 60
      min, or (ii) digestion with 0.25% trypsin for 60 or 120 min. RESULTS: Microwave
      treatment plus protease digestion for 30 or 60 min and trypsin digestion for 120
      min provided good results for the unmasking of immunoglobulins in glomeruli with
      structural preservation. The IgA deposits in IgA nephritis and IgG deposits in
      lupus nephritis and membranous nephropathy were clearly revealed in more than 80%
      of cases by both pretreatments. Microwave treatment plus protease digestion for
      30 min revealed the deposition of C3 in all cases of mesangiocapillary
      glomerulonephritis and lupus nephritis and was superior to trypsin digestion.
      Characteristic patterns of C3 deposition were observed for these forms of
      glomerulonephritis, although C3 deposits in membranous nephropathy were detected
      in only 50% of cases. It was not possible to unmask all of the antigens in the
      glomeruli, especially those with weak immunofluorescence. CONCLUSION: Microwave
      treatment plus protease digestion is effective for the unmasking of antigens in
      paraffin sections and as useful for the diagnosis of immune-mediated
      glomerulonephritis as trypsin digestion.

PMID- 15958047
TI  - Clinical risk factors associated with bleeding after native kidney biopsy.
AB  - PURPOSE: To determine the effect of various risk factors on postbiopsy bleeding
      (PBB). PROCEDURE: A retrospective review of 645 native kidney biopsies carried
      out from 1981 to 2001 was conducted. Data regarding age, gender, race, prebiopsy
      blood pressure, history of hypertension, pre- and postbiopsy
      haemoglobin/haematocrit, serum creatinine and blood urea nitrogen (BUN) were
      collected. FINDINGS: The overall PBB complication rate was 6.2%. High blood
      pressure was associated with a high risk of bleeding (test for trend, P < 0.05).
      It increased when systolic blood pressure (SBP) was >160 mm of Hg, diastolic
      blood pressure (DBP) was >100 mm of Hg, or mean arterial pressure (MAP) was > or
      = 120 mm of Hg. In patients with a history of hypertension, the risk of PBB was
      3.74 times higher (P = 0.0001) than patients with no history of hypertension,
      irrespective of blood pressure at the time of biopsy. For patients with
      creatinine > 2 mg/dL, the risk ratio for PBB was 5.89 when compared with patients
      with creatinine < or = 2 mg/dL. Logistic regression analysis showed that a
      history of hypertension was associated with PBB, with an odds ratio of 1.89
      (confidence interval, 1.10-3.26, P < 0.03), and serum creatinine of > 2.0 mg/dL
      was associated with an odds ratio of 2.56 (confidence interval, 1.48-4.42, P =
      0.001) for PBB. CONCLUSIONS: The risk of PBB increases with high SBP, DBP or MAP.
      A history of hypertension and high serum creatinine are significant independent
      risk factors for PBB.

PMID- 15958048
TI  - Expression of Fas, Bcl-2 and p53 molecules in glomerulonephritis and their
      correlations with clinical and laboratory findings.
AB  - BACKGROUND AND AIM: Apoptosis plays a crucial role in glomerulonephritis (GN) as
      a regulatory mechanism and is controlled by various molecules including Fas
      antigen, Bcl-2 and p53 oncoproteins. The aim of the present study is to evaluate
      the correlation between the expression of these molecules and clinical and
      laboratory data in different types of GN. RESULTS: The expression of Fas antigen,
      Bcl-2 and p53 protein in five normal human kidney specimens and 55 tissues from
      patients with several types of GN were examined by immunohistochemistry and
      correlated with clinical and laboratory findings. The number of Fas-positive
      intraglomerular cells was significantly increased in proliferative GN when
      compared with non-proliferative cases. Numbers of Bcl-2- and p53-positive cells
      in proliferative GN were not different from the non-proliferative cases and there
      was no correlation between the changes in Fas, Bcl-2 and p53 themselves.
      Significant correlation of expression of these molecules with clinical and
      laboratory findings was not found, except between p53 and blood urea nitrogen
      levels. CONCLUSION: Apoptosis is a complex molecular process and the results of
      the present study should be supported with other methods to understand whether
      apoptosis contributes to progression or resolution of GN. Increased glomerular
      expression of Fas, Bcl-2 and p53 molecules in all types of GN might contribute
      new therapeutic approaches by modulating the expression of these molecules.

PMID- 15958049
TI  - Hypersensitivity reactions to the polysorbate contained in recombinant
      erythropoietin and darbepoietin.
AB  - The following case reports are of two patients who have developed
      hypersensitivity reactions to the red cell growth hormones, darbepoietin and
      erythropoietin. The subsequent skin testing and clinical course suggested that
      the cause of these reactions was due to the excipient polysorbate 80. This
      finding might have implications in the recent increase in the incidence of pure
      red cell aplasia.

PMID- 15958050
TI  - Epstein-Barr virus-related primary central nervous system lymphoma after
      cadaveric renal transplantation improved by treatment with high-dose methotrexate
      followed by irradiation.
AB  - A 57-year-old man was admitted to hospital because of motor aphasia on 16
      September 2000. He had an approximate 2-year history of haemodialysis treatment,
      since April 1997, and had received a cadaveric renal transplantation in July
      1999. Computed tomography and magnetic resonance imaging (MRI) revealed a mass
      with ringed enhancement in the left temporal-parietal lobe. Primary central
      nervous system (CNS) lymphoma (diffuse large B cell type) was diagnosed based on
      an open brain tumour biopsy. Epstein-Barr virus early RNA (EBER) in situ
      hybridization showed positive signals in the nuclei of the CNS lymphoma cells. A
      dose reduction of immunosuppressant and three series of high-dose methotrexate
      (MTX) therapy with leucovorine rescue followed by irradiation (whole brain
      irradiation, 30 Gy; partial brain tumour irradiation, 20 Gy) were carried out for
      his primary CNS lymphoma. The patient is currently in good condition (September
      2004) with no enlargement of the lymphoma, as examined by MRI every 3 months, and
      preserved renal function.

PMID- 15958051
TI  - Abstracts of the 3rd World Congress of Nephrology. June 26-30, 2005. Singapore.

PMID- 15958052
TI  - High susceptibility of human c-Ha-ras proto-oncogene transgenic rats to
      carcinogenesis: a cancer-prone animal model.
AB  - Transgenic animals carrying human c-Ha-ras proto-oncogene, v-Ha-ras transgenic
      mice, pim-1 transgenic mice and several knockout mice deficient of tumor
      suppressor genes, such as p53, have been shown to exhibit increased carcinogen
      susceptibility. As a result, studies into practical application and medium-term
      screening of environmental carcinogens are under way. Given the advantages of rat
      models characterized by larger organ size, abundant information regarding
      preneoplasias and virus-free constitution, we have concentrated on the generation
      of transgenic rats bearing copies of the human c-Ha-ras proto-oncogene and shown
      the Hras128 strain to be extremely sensitive to the induction of mammary
      carcinomas, and to a lesser extent, lesions in the urinary bladder, esophagus and
      skin. In most, if not all, the mammary cancers mutations of the transgene but not
      the endogenous H-ras gene are present, appearing to occur early in the process of
      tumorigenesis, which involves proliferation of cells in TEB and intraductal
      hyperplasia before carcinomas arise. Preliminary findings suggest that this is
      independent of endogenous ovarian hormones, although inhibited by soy isoflavones
      and promoted by atrazine and nonylphenols. Although further studies of the
      mechanisms are clearly necessary, the model appears to have great potential for
      screening purposes, not only for modifiers active in the breast, but also other
      organs where tumors characterized by ras gene mutations develop.

PMID- 15958053
TI  - Chemokines in tumor progression and metastasis.
AB  - Although chemokines have been thought of primarily as leukocyte attractants, a
      growing body of evidence indicates that they also contribute to a number of tumor
      related processes, such as tumor cell growth, angiogenesis/angiostasis, local
      invasion, and metastasis. The current knowledge of the possible involvement of
      chemokines and their receptors in these cellular events are reviewed here. The
      operating mechanism of chemokines in relation to metastatic processes in vivo are
      also discussed.

PMID- 15958054
TI  - Development and biological analysis of peritoneal metastasis mouse models for
      human scirrhous stomach cancer.
AB  - The number of published studies on peritoneal dissemination of scirrhous gastric
      carcinoma is very small as a result of the unavailability of highly reproducible
      animal models. Orthotopic implantation of HSC-44PE and HSC-58 (scirrhous gastric
      carcinoma-derived cell lines) cells into nude mice led to dissemination of the
      tumor cells to the greater omentum, mesenterium, peritoneum and so on, and caused
      ascites in a small number of animals. Cycles of isolation of the ascitic tumor
      cells and orthotopic inoculation of these cells were repeated in turn to animals.
      This was to isolate highly metastatic cell lines with a strong capability of
      inducing the formation of ascites (44As3 from HSC-44PE; 58As1 and 58As9 from HSC
      58). All three cell lines induced tumor formation at the site of orthotopic
      injection, and caused fatal cancerous peritonitis and bloody ascites in 90-100%
      of the animals approximately 3-5 weeks after the inoculation. When the parent
      cells were implanted, the animals became moribund in approximately 12-18 weeks,
      however, none of the animals developed ascites. Complementary DNA microarray and
      immunohistochemical analyses revealed differences in the expression levels of
      genes coding for the matrix proteinase, cell adhesion, motility, angiogenesis and
      proliferation between the highly metastatic- and parent-cell lines. The
      usefulness of this model for the evaluation of drugs was assessed by analyzing
      the stability of the metastatic potential of the cells and the reproducibility.
      Animals intravenously treated with CPT-11 and GEM showed suppressed tumor growth
      and significantly prolonged survival. The metastatic cell lines and the in vivo
      model established in the present study are expected to serve as a model of
      cancerous peritonitis developing from primary lesions, and as a useful means of
      clarifying the pathophysiology of peritoneal dissemination of scirrhous gastric
      carcinoma and the development of drugs for its treatment.

PMID- 15958055
TI  - Frequent KIT and epidermal growth factor receptor overexpressions in
      undifferentiated-type breast carcinomas with 'stem-cell-like' features.
AB  - It was hypothesized that four histopathological types or subtypes of breast
      carcinoma were undifferentiated types characterized by bidirectional
      differentiation toward both luminal epithelial and myoepithelial cells and had
      characteristic molecular changes: invasive ductal carcinoma (IDC) with a large
      central acellular zone, atypical medullary carcinoma (a subgroup in Grade 3 solid
      tubular carcinoma), matrix-producing carcinoma, and spindle-cell carcinoma (or
      carcinoma with spindle-cell metaplasia). In 32 cases of the undifferentiated type
      and 37 cases of the relatively differentiated types, we immunohistochemically
      examined the expressions of myoepithelial markers and KIT, epidermal growth
      factor receptor (EGFR), and c-erbB-2 oncoproteins. Vimentin, S-100, and alpha
      smooth muscle actin were positive in 28 (88%), 22 (69%), and 15 (47%) of the
      undifferentiated types, but were positive in seven (19%), one (3%), and one (3%)
      of relatively differentiated types (P < 0.0001). KIT and EGFR overexpressions
      were detected more frequently in the undifferentiated types (34 and 88%,
      respectively) than in relatively differentiated types (3 and 3%, respectively) (P
      < 0.0001, for both). In 11 (85%) of 13 cases with KIT overexpression, EGFR
      overexpression concurred. c-erbB-2 overexpression was almost equally detected in
      both the undifferentiated and relatively differentiated types, and did not
      correlate with KIT or EGFR overexpression. Phosphotyrosine was detected in 16
      (67%) of 24 cases with KIT, EGFR, and/or c-erbB-2 overexpression but only in six
      (18%) of 34 cases without KIT, EGFR, or c-erbB-2 overexpression (P = 0.0002). The
      undifferentiated-type breast carcinomas appeared to show mammary epithelial stem
      cell-like features, and they could be identified by KIT and/or EGFR
      overexpressions.

PMID- 15958056
TI  - TEL/ETV6 accelerates erythroid differentiation and inhibits megakaryocytic
      maturation in a human leukemia cell line UT-7/GM.
AB  - TEL/ETV6 accelerates erythroid differentiation in the murine erythroleukemia cell
      line. To clarify the effects of TEL on megakaryocytic maturation as well as
      erythroid differentiation, we chose the human leukemia cell line UT-7/GM that
      differentiates into the erythroid and megakaryocytic lineages by treatment with
      erythropoietin and thrombopoietin, respectively. Upon erythropoietin exposure,
      overexpressed TEL stimulated hemoglobin synthesis and accumulation of the
      erythroid differentiation-specific transcripts such as gamma-globin, delta
      aminolevulinic acid synthase-erythroid, and erythropoietin receptor. Moreover,
      the glycophorin A(+)/glycoprotein IIb(-) fraction appeared more rapidly in the
      TEL-overexpressing cells. Interestingly, overexpression of TEL was associated
      with lower levels of the megakaryocytic maturation-specific glycoprotein IIb and
      platelet factor 4 transcripts under the treatment with thrombopoietin.
      Consistently, the glycophorin A(-)/glycoprotein IIb(+) fraction increased more
      slowly in the TEL-overexpressing cells. Finally, expression of endogenous TEL
      proteins in UT-7/GM cells was down-regulated following erythropoietin and
      thrombopoietin exposure. All these data suggest that TEL may decide the fate of
      human erythrocyte/megakaryocyte common progenitors to differentiate towards the
      erythroid lineage and against the megakaryocytic lineage.

PMID- 15958058
TI  - Nano-sized fluorescent particles as new tracers for sentinel node detection:
      experimental model for decision of appropriate size and wavelength.
AB  - The concepts of made-to-order and low-invasiveness medicines are becoming widely
      accepted. A treatment for cancer, with minimum invasive surgery and without lymph
      nodes dissection based on sentinel lymph node (SN) navigation surgery, would
      adhere to these concepts. Dyes and/or radioisotopes are employed for SN detection
      in standard methods, however, each detection method has advantages and
      disadvantages. To make up for the disadvantages, we aimed at developing a new non
      invasive method using fluorescent beads of uniform nano-size that could
      efficiently visualize SN from outside the body, and conducted experiments to
      determine the appropriate size and fluorescent wavelength. We examined various
      bead sizes and fluorescent wavelengths. The sizes were 20, 40, 100 and 200 nm.
      The fluorescent peak wavelengths of the beads were yellow-green (515 nm), dark
      red (680 nm), far red (720 nm) and infrared (755 nm). The beads were
      subcutaneously injected into the foot pad of the hind leg of a rat, and followed
      by laser scanning of the inguinal area for fluorescence observation. The beads
      exhibited different times for the fluorescence detection according to their sizes
      and wavelength. The 40 nm beads were considered to be the most appropriate size
      for SN detection in rats. The wavelength of near infrared was effective for
      avoiding attenuation by the tissue. In conclusion, we confirmed that uniformly
      nano-sized fluorescent beads have the potential to be an alternative to existing
      tracers in the detection of the SN in animal experiments if we select the
      appropriate particle size and wavelength.

PMID- 15958057
TI  - Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I
      II, diffuse large B-cell lymphoma of the stomach.
AB  - CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by
      radiotherapy is regarded as standard care for localized aggressive lymphoma;
      however, prospective confirmation of its applicability to localized primary
      gastric lymphoma is inadequate, and most patients in Japan have been initially
      treated with gastrectomy. We conducted a multicenter phase II study to evaluate
      the feasibility and efficacy of the non-surgical treatment. Eligibility criteria
      required primary gastric diffuse large B-cell lymphoma, stage I-II(1), age 20-75,
      performance status 0-1 and adequate organ function. Treatment consisted of three
      cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty-five patients were
      enrolled between December 1999 and February 2003, and 52 eligible patients were
      analyzed. Patient characteristics were as follows: median age, 61 years; 28 men,
      24 women; 36 with stage I, 16 with stage II(1); 47 with a low International
      Prognostic Index (IPI) and five with a low-intermediate IPI. All but one patient
      completed planned treatment. No serious complications including massive
      hemorrhage or perforation were observed. A complete response was achieved in 48
      of the 52 patients (92%, 95% confidence interval: 82-98%) and progressive disease
      in three. Two patients underwent salvage gastrectomy due to disease persistence
      or recurrence. With a median follow-up period of 28 months, 2-year progression
      free and overall survivals were 88 and 94%, respectively. CHOP followed by
      radiotherapy is safe and highly effective in localized gastric diffuse large B
      cell lymphoma. This organ-preserving treatment should be considered as a very
      reasonable therapeutic option.

PMID- 15958059
TI  - Inhibition of protein synthesis and activation of stress-activated protein
      kinases by onnamide A and theopederin B, antitumor marine natural products.
AB  - During the course of screening for the agents that activate transforming growth
      factor-beta (TGF-beta) signaling cascade, onnamide A and theopederin B,
      heterocyclic compounds related to mycalamides from a marine sponge, were found to
      induce plasminogen activator inhibitor-1 (PAI-1) promoter-derived gene expression
      in Mv1Lu cells. The maximum induction of the PAI-1 promoter by onnamide A and
      theopederin B was observed at the concentrations of 50 nM and 2 nM, respectively.
      These compounds strongly inhibited protein synthesis at the 50% inhibitory
      concentrations of 30 nM for onnamide A and 1.9 nM for theopederin B, and induced
      activation of p38 mitogen-activated protein kinase and c-Jun NH2-terminal protein
      kinase (JNK). Anisomycin, a well-known inducer of ribotoxic stress that inhibits
      protein synthesis and activates both p38 kinase and JNK, also activated PAI-1
      gene expression. Furthermore, PAI-1 expression by onnamide A, theopederin B, and
      anisomycin was inhibited by SB202190 and SP600125, specific inhibitors of stress
      activated protein kinases. Onnamide A and theopederin B were cytotoxic to a
      variety of cell lines and strongly induced apoptosis in HeLa cells within 24 h,
      which was accompanied by the sustained activation of p38 kinase and JNK. These
      results suggest that onnamide A and theopedirin B trigger a ribotoxic stress-like
      response, thereby inducing p38 kinase and JNK activation, the kinase-dependent
      PAI-1 gene expression, and apoptosis.

PMID- 15958060
TI  - Cytotoxic effects of pemetrexed in gastric cancer cells.
AB  - Pemetrexed is a newly developed multitargeted antifolate with promising clinical
      activity in many solid tumors including gastric cancer. The aim of the present
      study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction
      with cisplatin in gastric cancer cell lines, and to identify genes associated
      with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed
      by tetrazolium-based colorimetric assay (MTT assay) and the interaction between
      pemetrexed and cisplatin was evaluated by the isobologram method. Western
      immunoblotting and real time RT-PCR analysis of thymidylate synthase (TS),
      folylpoly-gamma-glutamate synthetase (FPGS) and reduced folate carrier (RFC1)
      were performed in order to determine whether sensitivity to pemetrexed would be
      predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic
      than 5-fluorouracil, with IC50 between 17 and 310 nM in most of the gastric
      cancer cell lines examined and the pemetrexed/cisplatin combination resulted in
      additive or synergistic interaction. The protein expressions of TS, FPGS, and
      RFC1 were significantly associated with IC50 for 5-fluorouracil, but no such
      association was found for pemetrexed chemosensitivity. The mRNA expressions of
      RFC1, FPGS and other target and resistance related genes revealed no significant
      association with pemetrexed sensitivity. In conclusion, pemetrexed is active
      against gastric cancer cell lines and the pemetrexed/cisplatin combination showed
      a synergistic or additive interaction, supporting its clinical use in gastric
      cancer. Drug sensitivity toward pemetrexed could not be predicted by the
      expressions of TS, RFC1, or FPGS and we suggest that it is determined by
      interactions between multiple genes.

PMID- 15958061
TI  - Cepharanthine potently enhances the sensitivity of anticancer agents in K562
      cells.
AB  - A major impediment to cancer treatment is the development of resistance by the
      tumor. P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) are
      involved in multidrug resistance. In addition to the extrusion of
      chemotherapeutic agents through these transporters, it has been reported that
      there are differences in the intracellular distribution of chemotherapeutic
      agents between drug resistant cells and sensitive cells. Cepharanthine is a plant
      alkaloid that effectively reverses resistance to anticancer agents. It has been
      previously shown that cepharanthine is an effective agent for the reversal of
      resistance in P-gp-overexpressing cells. Cepharanthine has also been reported to
      have numerous pharmacological effects besides the inhibition of P-gp. It has also
      been found that cepharanthine enhanced sensitivity to doxorubicin (ADM) and
      vincristine (VCR), and enhanced apoptosis induced by ADM and VCR of P-gp negative
      K562 cells. Cepharanthine changed the distribution of ADM from cytoplasmic
      vesicles to nucleoplasm in K562 cells by inhibiting the acidification of
      cytoplasmic organelles. Cepharanthine in combination with ADM should be useful
      for treating patients with tumors.

PMID- 15958062
TI  - Tumorigenesis facilitated by Pten deficiency in the skin: evidence of p53-Pten
      complex formation on the initiation phase.

PMID- 15958063
TI  - Haematopoietic stem cell transplantation in the treatment of severe autoimmune
      disease: results from phase I/II studies, prospective randomized trials and
      future directions.
AB  - Around 700 patients have received an autologous haematopoietic stem cell
      transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority
      of these have been within the context of phase I/II clinical trials and following
      international guidelines proposed 7 years ago. In general, a positive
      benefit/risk ratio has led to phase III prospective randomized controlled trials
      in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis
      (RA) in Europe. In the US, similar trials are being planned for SSc, MS and
      systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen
      in all disease subgroups since the inception due to more appropriate patient
      selection, and so far a clear advantage of the more intense myeloablative
      regimens in terms of remission induction and relapse rate has not emerged.
      Although each AD has a different profile, over a third of patients have sustained
      a durable remission, often with no further need for immunosuppressive drugs. In
      those who relapsed, many responded to agents which pre transplant had been
      ineffective. The study of immune reconstitution and gene expression pre and post
      HSCT is being undertaken to further understand the mechanism of autoimmunity.

PMID- 15958065
TI  - Viruses contribute to the development of Sjogren's syndrome.

PMID- 15958064
TI  - T cell-mediated immune responses in human newborns: ready to learn?
AB  - Infections with intracellular pathogens are often more severe or more prolonged
      in young infants suggesting that T cell-mediated immune responses are different
      in early life. Whereas neonatal immune responses have been quite extensively
      studied in murine models, studies of T cell-mediated immunity in human newborns
      and infants are scarce. Qualitative and quantitative differences when compared
      with adult immune responses have been observed but on the other hand mature
      responses to certain vaccines and infectious pathogens were demonstrated during
      the postnatal period and even during foetal life. Herein, we review the evidence
      suggesting that under appropriate conditions of stimulation, protective T cell
      mediated immune responses could be induced by vaccines in early life.

PMID- 15958066
TI  - Immunogenicity and protective efficacy of the Mycobacterium tuberculosis fadD26
      mutant.
AB  - The Mycobacterium tuberculosis fadD26 mutant has impaired synthesis of
      phthiocerol dimycocerosates (DIM) and is attenuated in BALB/c mice. Survival
      analysis following direct intratracheal infection confirmed the attenuation: 60%
      survival at 4 months post-infection versus 100% mortality at 9 weeks post
      infection with the wild-type strain. The fadD26 mutant induced less pneumonia and
      larger DTH reactions. It induced lower but progressive production of interferon
      (IFN)-gamma, interleukin (IL)-4 and tumour necrosis factor (TNF)-alpha. Used as a
      subcutaneous vaccine 60 days before intratracheal challenge with a hypervirulent
      strain of M. tuberculosis (Beijing code 9501000), the mutant induced a higher
      level of protection than did Bacille Calmette-Guerin (BCG). Seventy per cent of
      the mice vaccinated with the fadD26 mutant survived at 16 weeks after challenge
      compared to 30% of those vaccinated with BCG. Similarly, there was less tissue
      damage (pneumonia) and lower colony-forming units (CFU) in the mice vaccinated
      with the fadD26 mutant compared to the findings in mice vaccinated with BCG.
      These data suggest that DIM synthesis is important for the pathogenicity of M.
      tuberculosis, and that inactivation of DIM synthesis can increase the
      immunogenicity of live vaccines, and increase their ability to protect against
      tuberculosis.

PMID- 15958067
TI  - Enhanced clearance of Candida albicans from the oral cavities of mice following
      oral administration of Lactobacillus acidophilus.
AB  - Orally administered live Lactobacillus acidophilus was assessed for its capacity
      to enhance clearance from the oral cavity of DBA/2 mice shown previously to be
      'infection prone'. L. acidophilus fed to DBA/2 mice significantly shortened the
      duration of colonization of the oral cavity compared to controls. Enhanced
      clearance of Candida albicans correlated with both early mRNA gene expression for
      interleukin (IL)-4 and interferon (IFN)-gamma and expression of their secreted
      products in cultures of cervical lymph nodes stimulated with Candida antigen. In
      addition rapid clearance correlated with higher levels of IFN-gamma and nitric
      oxide in saliva. Delayed clearance, less pronounced levels of the cytokine
      response, saliva IFN-gamma and nitric oxide, and later mRNA expression for IL-4
      and IFN-gamma relative to feeding with the L. acidophilus isolate were noted in
      mice fed a different Lactobacillus isolate (L. fermentum). These observations
      indicate significant variations in individual isolates to activate the common
      mucosal system.

PMID- 15958068
TI  - Acellular Bordetella pertussis vaccine enhances mucosal interleukin-10
      production, induces apoptosis of activated Th1 cells and attenuates colitis in
      Galphai2-deficient mice.
AB  - Mice deficient for the inhibitory G protein subunit alpha2 (Galphai2(-/-))
      spontaneously develop a progressive inflammatory bowel disease resembling
      ulcerative colitis, and have a T helper 1 (Th1)-dominated immune response prior
      to onset of colitis, which is further augmented after the onset of disease. The
      present study was performed to investigate whether the Galphai2(-/-) mice were
      able to down-regulate the Th1-dominated inflammatory mucosal immune response
      and/or induce an anti-inflammatory Th2/T regulatory response and thereby diminish
      the severity of colitis following treatment with acellular Bordetella pertussis
      vaccine. The acellular vaccine against B. pertussis, the causative agent of
      whooping cough, has been demonstrated to induce a Th2-mediated response in both
      man and mice. We therefore treated Galphai2(-/-) mice intraperitoneally with a
      three-component acellular B. pertussis vaccine. The treated Galphai2(-/-) mice
      showed significantly increased interleukin (IL)-10 production in intestinal
      tissue, associated with significantly reduced colitis and decreased mortality,
      compared to untreated Galphai2(-/-) mice. The attenuation of colitis in Galphai2(
      /-) mice was due, at least partly, to the B. pertussis surface antigen
      filamentous haemagglutinin (FHA), which almost completely inhibited proliferation
      of CD4(+) T cells and stimulated apoptosis of activated CD4(+) T helper 1 cells.
      In conclusion, the three-component acellular B. pertussis vaccine containing
      filamentous haemagglutinin increases the production of IL-10 in the intestinal
      mucosa, induces apoptosis of activated Th1 cells and attenuates colitis in
      Galphai2(-/-) mice.

PMID- 15958069
TI  - TCR Valpha14 natural killer T cells function as effector T cells in mice with
      collagen-induced arthritis.
AB  - Natural killer (NK) T cells are a unique, recently identified cell population and
      are suggested to act as regulatory cells in autoimmune disorders. In the present
      study, designed to investigate the role of NKT cells in arthritis development, we
      attempted to induce arthritis by immunization of type II collagen (CIA) in
      Jalpha281 knock out (NKT-KO) and CD1d knock out (CD1d-KO) mice, which are
      depleted of NKT cells. From the results, the incidence of arthritis (40%) and the
      arthritis score (1.5 +/- 2.2 and 2.0 +/- 2.7) were reduced in NKT-KO and CD1d-KO
      mice compared to those in respective wild type mice (90%, 5.4 +/- 3.2 and 2.0 +/-
      2.7, P < 0.01). Anti-CII antibody levels in the sera of NKT-KO and CD1d-KO mice
      were significantly decreased compared to the controls (OD values; 0.32 +/- 0.16
      and 0.29 +/- 0.06 versus 0.58 +/- 0.08 and 0.38 +/- 0.08, P < 0.01). These
      results suggest that NKT cells play a role as effector T cells in CIA. Although
      the cell proliferative response and cytokine production in NKT-KO mice after the
      primary immunization were comparable to those in wild type mice, the ratios of
      both activated T or B cells were lower in NKT-KO mice than wild type mice after
      secondary immunization (T cells: 9.9 +/- 1.8% versus 16.0 +/- 3.4%, P < 0.01, B
      cells: 4.1 +/- 0.5% versus 5.1 +/- 0.7%, P < 0.05), suggesting that inv-NKT cells
      contribute to the pathogenicity in the development phase of arthritis. In
      addition, IL-4 and IL-1beta mRNA expression levels in the spleen during the
      arthritis development phase were lower in NKT-KO mice, while the IFN-gamma mRNA
      expression level was temporarily higher. These results suggest that inv-NKT cells
      influence cytokine production in arthritis development. In conclusion, inv-NKT
      cells may promote the generation of arthritis, especially during the development
      rather than the initiation phase.

PMID- 15958070
TI  - In vivo tumouricidal effects of LAD-1 monoclonal antibody on murine RL-male-1
      lymphoma mediated by enhanced phagocytosis.
AB  - We have reported previously that the LAD-4 monoclonal antibody (mAb) directed
      against a fibronectin receptor (FNR) on RL-male-1 T lymphoma cells in BALB/c mice
      partially inhibited their migration to the liver. In the present study, we
      examined the mechanism by which another anti-FNR mAb, LAD-1, exerts its
      antitumourigenic effects. Administration of LAD-1 significantly prolonged
      survival of BALB/c mice challenged previously with RL-male-1 cells. LAD-1
      enhanced phagocytosis of RL-male-1 cells by hepatic macrophages and clodronate
      mediated macrophage depletion abrogated the antitumour activity of LAD-1. In
      vitro experiments revealed that a pan-caspase inhibitor, zVAD-fmk, did not affect
      the ability of LAD-1 to inhibit the proliferation of RL-male-1 cells. These data
      suggest that the antitumour effects of LAD-1 may be dependent on stimulation of
      tumour cell phagocytosis and are apoptosis-independent. Thus, LAD-1-induced
      phagocytosis of lymphoma cells by hepatic macrophages in mice may, at least in
      part, be responsible for the prolonged survival of the mice.

PMID- 15958071
TI  - Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella
      induced interleukin-8 secretion in enterocyte-like Caco-2 cells.
AB  - Intestinal epithelial cells secrete the chemokine interleukin (IL)-8 in the
      course of inflammation. Because heat shock proteins (Hsps) and butyrate confer
      protection to enterocytes, we investigated whether they modulate Salmonella
      enterica serovar Enteritidis (S. serovar Enteritidis)-induced secretion of IL-8
      in enterocyte-like Caco-2 cells. Caco-2 cells incubated with or without butyrate
      (0-20 m M, 48 h) were infected with S. serovar Enteritidis after (1 h at 42
      degrees C, 6 h at 37 degrees C) or without prior heat shock (37 degrees C).
      Levels of Hsp70 production and IL-8 secretion were analysed using immunostaining
      of Western blots and enzyme-linked immunosorbent assay (ELISA), respectively. The
      cells secreted IL-8 in response to S. serovar Enteritidis and produced Hsp70
      after heat shock or incubation with butyrate. The IL-8 secretion was inhibited by
      heat shock and butyrate concentrations as low as 0.2 m M for crypt-like and 1 m M
      for villous-like cells. In a dose-dependent manner, higher butyrate
      concentrations enhanced IL-8 secretion to maximal levels followed by a gradual
      but stable decline. This decline was associated with increasing production of
      Hsp70 and was more vivid in crypt-like cells. In addition, the higher
      concentrations abolished the heat shock inhibitory effect. Instead, they promoted
      the IL-8 production in heat-shocked cells even in the absence of S. serovar
      Enteritidis. We conclude that heat shock and low concentrations of butyrate
      inhibit IL-8 production by Caco-2 cells exposed to S. serovar Enteritidis. Higher
      butyrate concentrations stimulate the chemokine production and override the
      inhibitory effect of the heat shock. The IL-8 down-regulation could in part be
      mediated via production of Hsp70.

PMID- 15958072
TI  - Engineering and functional evaluation of a single-chain antibody against HIV-1
      external glycoprotein gp120.
AB  - The HIV-1 envelope glycoprotein surface subunit gp120 is an attractive target for
      molecular intervention. This is because anti-HIV-1 gp120 neutralizing antibodies
      display the potential ability to inhibit HIV-1 infection. The present
      investigation describes the construction of a genetically engineered single chain
      antibody (scFv102) against HIV-1 gp120, its expression and functional evaluation.
      The parental hybridoma cell line (102) produces an immunoglobulin directed
      against the conserved CD4-binding region of gp120. cDNAs encoding the variable
      regions of the heavy (V(H)) and light (V(L)) chains were prepared by reverse
      transcription PCR and linked together with an oligonucleotide encoding a linker
      peptide (Gly(4)Ser)(3) to produce a single chain antibody gene. The resulting DNA
      construct was cloned into a prokaryotic expression vector (pET28) and recombinant
      scFv102 was expressed in Eserichia coli as an insoluble protein. The denatured
      scFv102 was refolded and purified by immobilized metal ion affinity
      chromatography. Purified scFv102 had the same specificity as the intact IgG in
      immuno-blotting assays and immuno-fluorescence (IF) detection, but ELISA analyses
      demonstrated the affinity of scFv102 to be 5-fold lower than that of the parental
      monoclonal antibody. In neutralization assays, scFv102 at concentrations lower
      than 40 microg/ml exhibited efficient interference with viral replication and
      inhibition of viral infection (90%) across a range of primary isolates of subtype
      B HIV-1. These results suggest that the constructed anti-HIV-1 gp120 scFv102 has
      good biological activity and can potentially be used for in vitro diagnostic and
      in vivo therapeutic applications.

PMID- 15958073
TI  - Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted
      hepatitis C virus epitopes after sustained virus loss.
AB  - Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may
      account for the outcome of interferon monotherapy. To investigate this
      hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized
      epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide
      complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in
      response to plastic-bound monomeric HLA/peptide complex was observed frequently
      in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296
      1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%),
      while no interferon-gamma production was observed in non-responders (NR) (n = 13)
      for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells
      specific for all the peptides except NS31296-1304 in two SVR at the end of
      interferon monotherapy, although hardly any such cells were found in four NR.
      Specific killing was observed against peptides NS31296-1304 (3/4) and core 129
      137 (1/4) in sustained responders but none in non-responders. These results
      suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during
      interferon therapy in these patients and that interferon-gamma production by
      CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well
      maintained in patients with SVR compared with those with NR. These findings
      emphasize the importance of the CD8(+) T cell response in controlling HCV
      infection.

PMID- 15958075
TI  - Expression of tumour necrosis factor receptor and Toll-like receptor 2 and 4 on
      peripheral blood leucocytes of human volunteers after endotoxin challenge: a
      comparison of flow cytometric light scatter and immunofluorescence gating.
AB  - Toll-like receptors (TLRs) are involved in the recognition of bacterial products
      and thus participate in the induction of the inflammatory cascade. However, much
      less is known about the evolution of leucocyte TLR expression during human
      inflammatory stress. We hypothesized that a decrease in leucocyte TLRs could
      account for the so-called tolerance or hyporesponsiveness state to subsequent
      stimulation with bacteria-derived products. Because of the profound monocytopenia
      that ensues after in vivo lipopolysaccharide (LPS) challenge, we also compared
      monocyte TLR expression using two different techniques of flow cytometric gating.
      In a first set of experiments, 17 healthy volunteers underwent LPS challenge.
      Blood was drawn at different time-points and analysed by flow cytometry using
      light scatter gating and one-colour analysis to assess the expression of the
      tumour necrosis factor receptor (TNFR) and TLR2 and TLR4 on both monocytes and
      granulocytes. In a second set of experiments, the assessment of those receptors
      was made using a more specific gating method that utilized light scatter and CD14
      immunofluorescence in a two-colour analysis. This was performed using whole blood
      drawn from five healthy volunteers and incubated ex vivo for different time
      periods with or without LPS and in 12 volunteers who underwent LPS challenge in
      vivo. The pattern of expression for monocyte TNFR was similar for both types of
      gating. Using only the light scatter gating, an initial drop of TLR 2 and 4 was
      observed on monocytes. By contrast, when using light scatter x immunofluorescence
      gating, an up-regulation of these two receptors following both in vivo and in
      vitro LPS exposure was observed. LPS up-regulates the expression of TLRs on
      monocytes and granulocytes. Depending upon the methodology utilized, contrasting
      results were obtained with respect to TLR2 and TLR4 expression. The flow
      cytometric gating technique used is of importance in determining cellular TLR2
      and TLR4 expression, especially in blood samples exhibiting significant
      monocytopenia.

PMID- 15958074
TI  - Innate immune responses in Lyme borreliosis: enhanced tumour necrosis factor
      alpha and interleukin-12 in asymptomatic individuals in response to live
      spirochetes.
AB  - Innate immunity is important for early defence against borrelia spirochetes and
      should play a role in the clinical outcome of the infection. In order to study
      early cytokine responses, in vitro differentiated dendritic cells (DCs) and whole
      blood cells from 21 patients with different clinical outcomes of Lyme
      neuroborreliosis were stimulated with live borrelia spirochetes. The borrelia
      induced secretion of interleukin (IL)-4, IL-10, IL-12p70, interferon (IFN)-gamma
      and tumour necrosis factor (TNF)-alpha in DCs and IL-1beta, IL-6, IL-8, IL-10, IL
      12p70, TNF-alpha, regulated upon activation normal T cell expressed and secreted
      (RANTES), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory
      protein (MIP)-1alpha, MIP-1beta and eotaxin in whole blood cells was measured by
      enzyme-linked immunospot (ELISPOT) and multiplex arrays, respectively. We found
      increased numbers of TNF-alpha-secreting DCs (P = 0.018) in asymptomatic
      seropositive individuals compared to patients with subacute neuroborreliosis and
      seronegative controls. Asymptomatic individuals were also found to have elevated
      levels of IL-12p70 (P = 0.031) in whole blood cell supernatants compared to
      seronegative controls. These results are in line with previous experiments using
      cells of the adaptive immune response, indicating that strong T helper type 1
      (Th1) proinflammatory responses might be associated with a successful resolution
      of Lyme disease.

PMID- 15958076
TI  - Interleukin-4 induced down-regulation of skin homing receptor expression by human
      viral-specific CD8 T cells may contribute to atopic risk of cutaneous infection.
AB  - Factors controlling the expression of cutaneous lymphocyte-associated antigen
      (CLA) by T cells are poorly understood, but data from murine and human CD4(+) T
      cell systems have suggested that cytokines play an important role. However, there
      are no data examining the influence of cytokines on the expression of CLA by
      human antigen-specific CD8(+) T cells. Peripheral blood mononuclear cells (PBMC)
      were isolated from 10 HLA-A*0201-positive healthy individuals. Using HLA-peptide
      tetrameric complexes refolded with immunodominant peptides from Epstein-Barr
      virus (EBV), cytomegalovirus (CMV) and influenza A virus, we investigated the
      temporal associations of CLA expression by viral-specific CD8(+) T cells
      following stimulation with antigen. Ex vivo influenza matrix-specific CD8(+) T
      cells expressed significantly (P < 0.05) greater levels of CLA than EBV BMLF1 and
      CMV pp65-specific CD8(+) T cells (mean 9.7% influenza matrix versus 1.4% BMLF1
      versus 1.1% pp65) and these differences were sustained on culture. However,
      regardless of viral specificity, interleukin (IL)-12 and IL-4 induced significant
      (P < 0.05) dose-dependent up-regulation and down-regulation of CLA expression,
      respectively, with IL-4 showing a dominant negative effect. In many cases, IL-4
      resulted in complete abrogation of detectable CLA expression by the viral
      specific CD8(+) T cells. Overall these data demonstrate that CLA expression by
      human viral-specific CD8(+) T cells is highly dynamic and that IL-4 causes
      significant down-regulation. Disorders associated with a type 2 cytokine shift
      may reduce the efficiency of skin homing by viral-specific CD8(+) T cells.
      Furthermore, the ability to modify the local and systemic microenvironment may
      offer novel therapeutic strategies that influence tissue-specific T cell homing.

PMID- 15958077
TI  - Analysis of circulating gammadelta T cells in children affected by IgE-associated
      and non-IgE-associated allergic atopic eczema/dermatitis syndrome.
AB  - Recent studies have suggested that not only alphabeta(+) T cells, but also the
      less common gammadelta(+) T cells may play a role as effectors and
      immunoregolatory cells in the development and perpetuation of allergic
      inflammation. The objective of this study was to focus on the role of
      gammadelta(+) T cells in atopic dermatitis (AD), a chronic relapsing inflammatory
      disease of the skin, often associated with allergic bronchial asthma. The present
      study employed flow cytometric analysis to compare numbers and phenotypic
      characteristics of gammadelta(+) T cells in the peripheral blood of children with
      atopic dermatitis and age-matched healthy controls. The percentage of circulating
      Vgamma 9Vdelta2(+) T lymphocytes was significantly increased in AD patients with
      respect to the age-matched controls, with a positive correlation with clinical
      score severity. The prevalent phenotype in both AD patients and controls was
      CD45RO(+), with no differences observed in the percentage of Vdelta2(+) CD45RO(+)
      between these groups. Conversely, memory CD45RO(+) CD62L(+) Vdelta2(+)
      lymphocytes were significantly lower in AD patients. Furthermore, naive
      circulating Vdelta2(+) T lymphocytes were significantly lower in AD children than
      in aged-matched controls. No correlation was observed between circulating Vgamma
      9Vdelta2(+) expansion and IgE serum levels. It was concluded that an association
      exists between the levels of circulating gammadelta(+) T lymphocytes and atopic
      dermatitis, with a positive correlation with clinical score but no link with IgE
      serum levels. The pathophysiological role of gammadelta T lymphocytes in atopic
      dermatitis awaits further investigation.

PMID- 15958078
TI  - Increased expression of plasma and cell surface co-stimulatory molecules CTLA-4,
      CD28 and CD86 in adult patients with allergic asthma.
AB  - The co-stimulatory interactions of the B7 family molecules CD80 and CD86 on
      antigen-presenting cells, together with their T cell counter receptors CD28 and
      cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), modulate T lymphocyte
      mediated immune responses in a reciprocal manner. To investigate whether there is
      altered expression and the clinical significance of soluble co-stimulatory
      molecules in asthmatic patients, plasma concentrations of sCTLA-4, sCD28, sCD80
      and sCD86 in 51 adult allergic asthmatic adults with or without steroid
      treatment, and 35 sex- and age-matched control subjects were measured by enzyme
      linked immunosorbent assay (ELISA). Cell surface expression of CTLA-4 and CD28 on
      peripheral blood mononuclear cells (PBMC) were analysed by flow cytometry.
      Results showed that the plasma sCTLA-4 concentration was significantly higher in
      all asthmatic patients while sCD28 and sCD86 concentrations were significantly
      higher in steroid and non-steroid treated asthmatic patients, respectively,
      compared with control subjects (all P < 0.01). Significantly increased cell
      surface expression of CD28 but not CTLA-4 on PBMC was found in asthmatic patients
      compared with controls (P < 0.05). The plasma concentration and cell surface
      expression of CTLA-4 were found to exhibit positive and significant correlations
      with those of CD28 (both P < 0.05). Serum total IgE concentration correlated
      positively and significantly with sCTLA-4 and sCD28 concentrations in allergic
      asthmatic patients (both P < 0.05). The increased expression of these soluble co
      stimulatory molecules may reflect the dysregulation of T cell activation, thereby
      contributing to the immunopathogenesis of allergic asthma.

PMID- 15958079
TI  - Diminished cytokine signalling against bacterial components in mononuclear
      leucocytes from ulcerative colitis patients after leukocytapheresis.
AB  - Infiltration by circulating inflammatory cells is a prominent local inflammatory
      feature of ulcerative colitis (UC). Several trials have suggested that
      leukocytapheresis by filtration can benefit patients with active UC. We
      investigated how this therapy might modulate the inflammatory response. Patients
      with active UC who were beginning repeated filtration leukocytapheresis were
      studied. Mononuclear cell preparations were obtained from blood before and after
      the first treatment, and expression of cytokine signalling components and the
      cell-proliferative response were analysed in vitro. Leukocytapheresis reduced
      lipopolysaccharide-induced production of proinflammatory cytokines (interleukin
      1, -6, -8 and tumour necrosis factor-alpha, P < 0.05 for all) and activation of
      intracellular signalling components (nuclear factor-kappaB, mitogen-activated
      protein kinases, and signal transducer and activator of transcription-3), as well
      as surface expression of toll-like receptor-4 (P < 0.05) in mononuclear cells.
      The therapy also reduced the cell-proliferative response by mononuclear cells
      stimulated with sonicated bacterial preparations from autologous intestine (P <
      0.05). These results indicate that activated mononuclear cells in the peripheral
      blood of patients with active UC are removed by leukocytapheresis and replaced by
      cells with a lower activation status. This replacement may partly explain the
      therapeutic benefit.

PMID- 15958080
TI  - Gene polymorphisms and serological markers of patients with active Crohn's
      disease in a clinical trial of antisense to ICAM-1.
AB  - Serological profiles for anti-Saccharomyces cerevisiae antibodies (ASCA)/
      perinuclear antineutrophil cytoplasmic antibodies (pANCA) and gene polymorphisms
      in tumour necrosis factor (TNF)-alpha and intercellular adhesion molecule-1 (ICAM
      1) are associated with occurrence and/or outcome in Crohn's disease. The aim of
      the study was to characterize the ASCA/pANCA profile, soluble ICAM-1 expression
      and single nucleotide gene polymorphisms (SNPs) in TNF-alpha and ICAM-1 genes.
      Crohn's patients with moderate disease activity were enrolled in a clinical trial
      of Alicaforsen (ISIS 2302). Peripheral blood samples were collected prospectively
      for serum studies and for potential analysis of gene polymorphisms. A
      multivariate analysis was performed to compare treatment effect with the
      biomarkers studied. Serological testing for ASCA/pANCA was obtained for 257
      patients at baseline: 37% were ASCA(+)/pANCA(-) (Crohn's pattern), 9% had both
      markers, 15% were ASCA(-)/pANCA(+) and 39% had neither marker. When the data were
      analysed by multiple regression analysis, a trend was found within the
      Alicaforsen-treated groups for greater rates of remission in the ASCA(+)/pANCA(-)
      subgroup versus all other serological profiles (25 versus 14%, P = 0.068), but
      not versus the placebo remission rate (18.8%). Gene polymorphisms were assessed
      in 64 patients, 21 from the placebo group. ICAM-1 assessment revealed no over
      representation. However, three unique TNF-alpha SNPs were identified that
      correlated significantly with remission; sites 290 (P = 0.0253), -2735 (P =
      0.0317) and -3090 (P = 0.0067). Although the overall clinical trial was negative,
      we have identified a trend towards clinical remission with Alicaforsen therapy in
      a subgroup of patients with Crohn's disease expressing ASCA(+)/pANCA(-).
      Furthermore, we have identified three TNF-alpha SNPs that may also predict a
      positive therapeutic outcome.

PMID- 15958081
TI  - Cross-reaction between antibodies to the major epitope of Ro60 kD autoantigen and
      a homologous peptide of Coxsackie virus 2B protein.
AB  - Coxsackie virus RNA has recently been detected in biopsy specimens of minor
      salivary glands from patients with primary Sjogren's Syndrome (pSS). A peptide
      derived from Coxsackie virus 2B protein (pepCoxs) presents 87% sequence homology
      with the 222-229 region of the major linear B-cell epitope of Ro60 kD autoantigen
      (pep216-232). Synthetic peptides corresponding to pep216-232:
      (216)KALSVETEKLLKYLEAV(232) and pepCoxs: (31)MVTSTITEKL LKNLVKI(47), were
      prepared. Sera from 42 patients with pSS and 43 patients with systemic lupus
      erythematosus (SLE) as well as sera from 27 healthy individuals (normal controls)
      and sera from 30 patients with rheumatoid arthritis (disease controls) were
      tested against the two homologous peptides. Twenty-five percent of SLE sera and
      33.3% of pSS sera reacted against pep216-232, whereas 28% of SLE sera and 37% of
      pSS sera recognized the pepCoxs. The sera reacting with pep216-232 were
      apparently the same as those reacting with pepCoxs. Normal sera and disease
      control sera presented only a limited reactivity against both peptides (ranging
      from 3.7% to 10%). Both peptides reacted more prominently with anti-Ro/La (+)
      sera from pSS patients. Thus, pep216-232 was recognized by 17% of the anti-Ro (+)
      sera and by 42% of the anti-Ro/La (+) sera, whereas pepCoxs was recognized by
      28.5% and 38% of the a-Ro(+) and a-Ro/La(+) sera, respectively. Purified anti
      pep216-232 antibodies readily reacted with both peptides while inhibition
      experiments revealed the specificity of this reaction. These results suggest a
      possible cross-reaction between antibodies to the major linear B-cell epitope of
      Ro60 kD autoantigen and the homologous pepCoxs in pSS patients. This cross
      reaction might potentially play a role in autoantibody formation and the
      perpetuation of the autoimmune response against Ro/SSA and La/SSB.

PMID- 15958082
TI  - Major immunoreactive domains of human ribosomal P proteins lie N-terminal to a
      homologous C-22 sequence: application to a novel ELISA for systemic lupus
      erythematosus.
AB  - The aim of this study was to identify immunoreactive domains on human ribosomal
      P0, P1 and P2 proteins, other than the C-22 peptide, to develop a novel ELISA
      using a combination of these proteins and to compare this ELISA with one using
      the C-22 peptide. Human recombinant P0, P1, P2 and mutant P0 lacking the
      homologous C-22 peptide (N-P0) were produced in bacteria and tested by ELISA and
      immunoblotting using sera from 48 patients with systemic lupus erythematosus
      (SLE), 48 with an unrelated inflammatory disorder (Crohn's disease) and 47
      healthy controls. ELISA with P0, P1 and P2, premixed at equimolar concentrations,
      gave higher OD readings than each protein tested individually. Eighteen SLE sera
      tested positive by ELISA with premixed P0, P1, P2 but only 3 tested positive with
      the C-22 peptide. Twenty-two SLE sera reacted positively, as determined by
      immunoblotting, with 5 different P protein combinations: P1P2, P0P1P2, P1, P0P1,
      P0 and P1. Only sera reactive with all three P proteins reacted with the C-22
      peptide, with absent or minimal reactivity with N-P0. Native antigens yielded
      sensitivity (6/48, 13%) similar to the C-22 peptide assay. An ELISA with premixed
      P1 and P2 gave higher OD values than the arithmetic means with P1 or P2. Fifteen
      SLE patients had antibodies to double stranded (ds)-DNA, of which 6 also had
      antibodies to P0P1P2 by ELISA but 12 reactive with P0P1P2 did not have
      discernable ds-DNA antibodies. Ribosomal P autoantibodies react mainly with
      epitopes N-terminal to a homologous C-22 peptide. An ELISA with premixed P0, P1
      and P2 has 5-fold greater sensitivity (38%) for SLE than an assay with the
      conventional C-22 peptide (7%). The combined sensitivity for SLE for antibodies
      to P0P1P2 and ds-DNA is 56%, higher than C-22 and ds-DNA, 38%. Only one of the
      SLE patients had neuropsychiatric lupus.

PMID- 15958083
TI  - Natural killer cell activity in families of patients with systemic lupus
      erythematosus: demonstration of a killing defect in patients.
AB  - Natural killer (NK) cell cytotoxic activity and cell frequency, expressed as a
      percentage of total lymphocytes, have been determined in peripheral blood
      mononuclear cells from first-degree relatives of patients with systemic lupus
      erythematosus (SLE), the patients themselves, a group of rheumatoid arthritis
      (RA) patients and controls. Low levels of killing activity relative to controls
      were found in some members of all groups with the extent of depression falling
      into two ranges. Moderate reductions were seen in female (3/31, 10%) and male
      (4/14, 29%) relatives of SLE patients, female (12/60, 20%) and male (3/4, 75%)
      SLE patients and female RA patients (6/17, 35%). A more profound depression of
      killing activity was confined to other female SLE patients (15/60, 25%). There
      were strong correlations in all groups between killing activity and percentage of
      NK cells, but analysis of the ratio of these parameters and studies with purified
      preparations of NK cells suggest that the reduced activity in SLE frequently
      involves a defect in the killing capacity of the individual cells in addition to
      the reduced levels of NK cells. Azathioprine (AZA), which was used in treatment
      of 12 SLE patients, was invariably associated with low values of killing
      activity. It appears to substantially reduce the percentage of NK and B cells in
      an action unconnected with the NK cell abnormalities associated with SLE. The
      finding of low killing activity in relatives and a correlation between their
      activity and that of their patients support the view that NK cell deficiency is a
      genetic determinant of SLE. NK cells in SLE may produce insufficient levels of
      cytokines required for the regulation of IgG production.

PMID- 15958084
TI  - Increased monocyte transcription of the proteinase 3 gene in small vessel
      vasculitis.
AB  - Proteinase 3 (PR3) is a pleiotropic and destructive serine protease and it is
      also a major target for autoantibodies in systemic small vessel vasculitis. We
      have shown recently that patients in stable remission have increased circulating
      levels of PR3, independent of autoantibody titre, inflammation, neutrophil
      degranulation and renal function. Here we explore the possibility of increased
      PR3 gene transcription. RNA was purified from peripheral blood monocytes from
      vasculitis patients and controls. Specific mRNA was measured by TaqMan real-time
      polymerase chain reaction (PCR). The monocyte-like cell lines THP-1 and U937 and
      human peripheral blod monocytes from healthy controls were stimulated with
      cytokines and lipopolysaccharide (LPS) for different time periods. PR3 protein
      was measured in plasma with enzyme-linked immunosorbent assay (ELISA). The median
      result for PR3 mRNA was 9.6 (1.8-680) for 22 patients, compared to 1 (0.1-2.8)
      for the 15 healthy controls. Elastase expression was also significantly
      increased, whereas myeloperoxidase and interleukin-8 were not. Stimulation of
      monocytes with tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma or LPS
      did not result in any increase of PR3 or elastase transcription, whereas
      interleukin (IL)-8 transcription was increased 10-fold. Circulating monocytes
      from patients with systemic vasculitis display increased PR3 gene transcription
      compared to healthy controls and patients with sytemic lupus erythematosus (SLE).
      This may be important for the development of vasculitis. Our results do not
      favour a role for cytokines, antineutrophil cytoplasmic antibodies (ANCA) or
      immunosuppressive medication in the upregulation of PR3 transcription in
      vasculitis.

PMID- 15958087
TI  - Statin administration prior to ischaemic stroke onset and survival: exploratory
      evidence from matched treatment-control study.
AB  - In addition to their lipid-lowering effects, it has been speculated that statins
      may also have beneficial effects on cerebral circulation and brain parenchyma
      during ischaemic stroke and reperfusion. We hypothesized that patients who had
      taken statins prior to stroke onset may have a better survival rate at 1 month
      and during the follow-up period. We retrospectively studied consecutive ischaemic
      stroke patients admitted to an acute stroke unit and at least a month's follow
      up. From these, we included those patients who, at admission, had reported the
      use of a statin prior to the stroke onset in the statin group (n = 205). Each
      patient in the statin group was matched with two patients who reported no statin
      use (n = 410). Using logistic regression and Cox proportional hazards models, we
      adjusted for variables that significantly differed between treatment groups or
      that independently predicted mortality. After adjusting for those variables,
      statin use was associated with reduced mortality at 1 month [odds ratio 0.24; 95%
      confidence interval (CI) 0.09-0.67] and during the follow-up period (hazard ratio
      0.57; 95% CI 0.35-0.93). The use of statins prior to stroke onset is associated
      with improved stroke survival within this cohort study with matched controls.

PMID- 15958085
TI  - Sustained activation of neutrophils in the course of Kawasaki disease: an
      association with matrix metalloproteinases.
AB  - Kawasaki disease (KD) is an acute febrile syndrome of childhood, characterized by
      vasculitis of the medium-sized arteries. White blood cell counts and the
      inflammatory parameter C-reactive protein (CRP) are known to be elevated in the
      acute phase of the disease. In this study we investigated the course of
      inflammatory cell type-specific parameters in KD over a longer period of time.
      Plasma levels of human neutrophil elastase (HNE), matrix metalloproteinases-2 and
      -9 (MMP2, MMP9), and neutrophil gelatinase-associated lipocalin (NGAL),
      macrophage neopterin and CRP were measured. Plasma samples were collected in the
      acute, subacute and early convalescent stage, and three months after the onset of
      disease. Median CRP and neopterin normalized within two weeks. In contrast, six
      weeks and three months after onset of disease, levels of HNE were still elevated,
      with median values of 163 ng/ml and 156 ng/ml, respectively (control children
      median < 50 ng/ml; for all time-points P < 0.0001). Values of NGAL correlated
      with the levels of HNE (r = 0.39, P = 0.013). These results demonstrate a longer
      state of neutrophil activation in KD than was previously assumed. The potential
      relationship between this prolonged neutrophil activation, coronary artery lesion
      formation and their persistence, as well as the risk of premature atherosclerosis
      warrants further evaluation.

PMID- 15958088
TI  - Ocular complications of neurological therapy.
AB  - Treatments used for several neurological conditions may adversely affect the eye.
      Vigabatrin-related retinal toxicity leads to a visual field defect. Optic
      neuropathy may result from ethambutol and isoniazid, and from radiation therapy.
      Posterior subcapsular cataract is associated with systemic corticosteroids.
      Transient refractive error changes may follow treatment with acetazolamide or
      topiramate, and corneal deposits and keratitis with amandatine. Intraocular
      pressure can be elevated in susceptible individuals by anticholinergic drugs,
      including oxybutynin, tolterodine, benzhexol, propantheline, atropine and
      amitriptyline, and also by systemic corticosteroids and by topiramate. Nystagmus,
      diplopia and extraocular muscle palsies can occur with antiepileptic drugs,
      particularly phenytoin and carbamazepine. Ocular neuromyotonia can follow
      parasellar radiation. Congenital ocular malformations can result from in utero
      exposure to maternally prescribed sodium valproate, phenytoin and carbamazepine.
      Neurologists must be aware of potential ocular toxicity of these drugs, and
      appropriately monitor for potential adverse events.

PMID- 15958089
TI  - Risk factors from brain tumors in children and adolescents: a case-control study
      in Belgrade, Serbia.
AB  - The objective of the present study was to test the different hypotheses about
      factors related to the occurrence of brain tumors in children and adolescents.
      The case-control study of brain tumors was conducted in Belgrade (Serbia) from
      1998 through 2000. The study group consisted of 60 newly diagnosed brain tumor
      patients and the same number of hospital controls. In the analysis conditional
      univariate and multivariate logistic regression were applied. According to the
      final model of multivariate analysis the following factors were significantly
      related to brain tumors: schooling of father <14 years (OR = 11.05, 95% CI 2.41
      50.63, P = 0.002), mothers - housewives or workers versus clerks (OR = 2.62, 95%
      CI 1.06-6.57, P = 0.036), number of brothers and sisters greater than one (OR =
      3.02, 95% CI 1.50-7.22, P = 0.001), and more frequent presence of malignant
      diseases, including brain tumors, in family history (OR = 3.54, 95% CI 1.30-9.60,
      P = 0.001). This case-control study was made to investigate different factors of
      possible importance for brain tumors in children and adolescents. Lower family
      social status, and more frequent occurrence of malignant tumors amongst relatives
      seem to be the factors that contribute the most to the higher risk of brain
      tumors.

PMID- 15958090
TI  - Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype
      in benign vs. progressive multiple sclerosis.
AB  - The majority of patients with multiple sclerosis (MS) experience gradual
      progression of disability, either as secondary progressive MS (SPMS) or primary
      progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign
      course with little or no disease progression and minimal disability decades after
      the first manifestations, so called benign MS (BMS). In our search to identify
      factors that are associated with progression of MS, we investigated serum levels
      of uric acid and dehydroepiandrostenedione sulphate (DHEAS), and apolipoprotein
      (apo)E genotype in 28 patients with BMS, 33 with SPMS, 21 with PPMS, and 29
      healthy individuals. We found no significant changes in uric acid levels and apoE
      genotype between the four groups. Mean DHEAS levels were lower in MS patients
      compared with healthy controls (P = 0.049), but there were no significant
      differences between the clinical subgroups of MS. In patients with SPMS and PPMS
      there was no correlation between progression rate and serum levels of either uric
      acid or DHEAS. Our results suggest that serum levels of uric acid and DHEAS, and
      apoE genotype do not differ between patients with a benign and progressive course
      of MS.

PMID- 15958091
TI  - Prognostic factors and therapeutic outcome of isolated symptomatic middle
      cerebral artery stenosis.
AB  - To analyze the prognostic factors and therapeutic outcome of adult patients with
      isolated symptomatic stenosis of the middle cerebral artery (MCA). Forty-nine
      patients were retrospectively verified with isolated symptomatic stenosis of the
      MCA through both magnetic resonance angiogram and transcranial color-coded duplex
      sonography. Therapeutic outcome at 1 year or more was determined using a modified
      Barthel index (BI). For the purpose of analysis, the patients were divided into
      two groups: a good outcome group (BI > or = 12) and a poor outcome group (BI < 12
      or recurrent stroke). The association between different therapeutic regimens and
      the percent free of recurrent stroke after the first event of cerebral infarction
      was assessed with Kaplan-Meier plots compared by a log-rank test. These patients
      accounted for 2.8% of all patients with the first event of cerebral infarction
      during the same period. At follow-up of 1 year or more, 63% had good outcomes
      whilst the other 37% had poor outcomes. Overall, 26.5% suffered from recurrent
      strokes during the follow-up period. According to the statistical analysis, the
      stepwise logistic regression revealed that only the National Institutes of Health
      Stroke Scale (NIHSS) at the time of admission was independently associated with a
      poor outcome. Furthermore, Kaplan-Meier analysis showed a significantly higher
      percentage of patients free of recurrent stroke events amongst those who were
      treated with warfarin. The NIHSS at the time of admission was a predictor of
      outcome amongst our patients, and stenosis of the MCA implies the danger of
      recurrent cerebral events. Our study also demonstrates the efficacy of oral
      anticoagulants in the secondary prevention in this specific group of patients.
      Therefore, we look forward to more prospective multicenter investigations in
      evaluating the efficiency of therapy in the future.

PMID- 15958092
TI  - Correlation between the IgG index, oligoclonal bands in CSF, and the diagnosis of
      demyelinating diseases.
AB  - Intrathecal immunoglobulin synthesis can be assessed by different approaches. It
      can be measured quantitatively by the IgG index or qualitatively by isoelectric
      focusing (IEF) to detect oligoclonal bands (OCB). In this study we investigated
      if there is a correlation between the frequency of OCB and the IgG index and if
      the IgG index predicts the diagnosis of a demyelinating CNS disease (DMD). We
      found a positive correlation between the IgG index and the frequency of OCB as
      well as the probability of DMD. We conclude that quantitative assessment of CSF
      IgG can be useful because it is easier and quicker to perform than IEF but cannot
      replace IEF in general because this is the most sensitive method to detect
      abnormal IgG in CSF.

PMID- 15958093
TI  - Study of plasma antioxidant status in Alzheimer's disease.
AB  - To examine the plasma antioxidant status of Alzheimer's disease (AD) patients and
      to evaluate the influence of apolipoprotein E (APOE) genotype. There are reasons
      to suspect involvement of the free hydroxyl radical in the pathogenesis of AD. In
      contrast, studies in plasma of AD patients for the evaluation of levels of
      biomarkers of oxidation are controversial. Twenty AD patients diagnosed using the
      National Institute for Neurological Disorders/Alzheimer's Disease and Related
      Disorders (NINDS/ADRDA) criteria and 22 controls chosen amongst different
      subjects without cognitive damage. All the subjects--both AD patients and
      controls--were stratified by their APOE genotype (3/3, 3/4 or 4/4), which was
      determined by PCR. Plasma total antioxidant capacity (TAC) was determined using
      two complementary procedures: FRAP, which measures the ferric reduction capacity,
      and ABTS, which measures the radical scavenging capacity. In addition, 2-amino
      adipic semialdehyde (2-AAS), a biomarker of protein oxidation, was evaluated. No
      significant difference was observed between the AD and control groups regarding
      plasma TAC. When the subjects were classified by their APOE genotype, significant
      differences were found in the APOE 4/4 group in the TCA determined by the FRAP
      method. Subjects with APOE genotype 4/4, which is the group with higher incidence
      in AD, showed lower antioxidant capacity of plasma. It is the first time that
      antioxidant capacity in plasma is evaluated in AD patients characterized by their
      APOE genotypes.

PMID- 15958094
TI  - Clinical experience with linezolid for the treatment of central nervous system
      infections.
AB  - Linezolid, an oxazolidinone, exhibits bacteriostatic activity against virtually
      all Gram-positive bacteria and even covers atypical organisms like mycobacteria
      and Nocardia. However, little is known about its effectiveness for central
      nervous system (CNS) infections. We report on our good experience with linezolid
      for the treatment of CNS infections in 10 patients, amongst whom three were
      caused by mycobacteria. While six of our patients clinically improved during
      linezolid therapy even after failure of various antibiotics, it was unsuccessful
      in one case. Side-effects were only mild gastrointestinal problems in one patient
      after long term-treatment, which however led to the cessation of therapy.
      Linezolid appears to be a safe alternative to vancomycin for therapy-resistant
      CNS infections because of its good CSF penetration and few side-effects.

PMID- 15958095
TI  - Increased muscular and cutaneous pain sensitivity in cephalic region in patients
      with chronic tension-type headache.
AB  - Increased excitability of the central nervous system generated by repetitive and
      sustained pericranial myofascial nociception may be responsible for
      transformation of episodic tension-type headache into chronic form. We aimed to
      compare mechanical and electrical (intramuscular and cutaneous) pain thresholds
      in trapezius and anterior tibial regions between 20 patients with chronic tension
      type headache and 20 healthy controls. Pain thresholds to three types of
      electrical stimulation (single pulse, 2 and 100 Hz) were significantly lower in
      patients than in controls in trapezius muscle (P < 0.02) and in skin overlying
      the trapezius muscle (P < 0.05), whilst electrical pain thresholds did not differ
      between groups in anterior tibial muscle and skin. Quantitative sensory testing
      revealed increased pain sensitivity in patients as assessed by pressure
      controlled manual palpation (local tenderness score, LTS; P < 0.01) and by
      pressure algometry (mechanical pain thresholds; P < 0.05) in test areas over the
      trapezius muscle, but not the anterior tibial muscle. In summary, this study
      demonstrates lower pain thresholds in muscle and skin of the cephalic region but
      not in lower limb muscle and skin in patients with chronic tension-type headache
      than in healthy controls. Increased sensitivity in nociceptive pathways from
      cephalic region may be of importance in the pathophysiology of chronic tension
      type headache.

PMID- 15958096
TI  - Long-term effects of intravenous high dose methylprednisolone pulses on bone
      mineral density in patients with multiple sclerosis.
AB  - To determine the effects of high dose methylprednisolone (HDMP) pulses on bone
      mineral density (BMD) in patients with multiple sclerosis (MS), we studied 25 MS
      patients who received regular pulses of HDMP as well as pulses of HDMP for
      relapses, 18 MS patients who received HDMP at the same dose schedule only for
      relapses, and 61 healthy controls. We measured BMDs at lumbar spine and femoral
      neck and we assessed biochemical markers of bone metabolism and turnover. The
      average lifetime dosage of MP was 75.4 (SD 11.9) g in the pulsed HDMP group and
      28.6 (SD 18.3) g in the HDMP for relapses group (P < 0.0001). Two MS patients
      (4.7%) and four controls (6.6%) had osteoporosis (P = NS), whereas 25 patients
      with MS (58.1%) and 21 controls (34.4%) had osteopenia (P = 0.016). BMDs measured
      at lumbar spine and femoral neck and biochemical indices of bone metabolism did
      not differ in MS patients and controls. BMD measures were not associated with
      lifetime methylprednisolone dosage. In partial correlation analysis, controlling
      for age, gender and menopausal status there was a significant inverse correlation
      between BMD at femoral neck and Expanded Disability Status Scale (EDSS) score (r
      = -0.31, P = 0.05). In conclusion, treatment with repeated HDMP pulses was not
      associated with osteoporosis in patients with MS who participated in a trial of
      methylprednisolone. However, osteopenia was observed more frequently in MS
      patients than healthy controls. Our data are reassuring, as them suggest that
      repeated pulses of methylprednisolone do not result in substantially increased
      risk of osteoporosis in MS patients. Moreover, osteopenia was found only in
      patients treated for relapses, who had a significantly higher EDSS score than
      patients in the HDMP group, suggesting that decreased mobility may contribute to
      bone loss more than corticosteroid use. BMD should be monitored in patients with
      MS, regardless of the use of methylprednisolone.

PMID- 15958097
TI  - Multiple attack study on the available triptans in Italy versus placebo.
AB  - The aim of the study is to evaluate the efficacy and tolerability of the five
      triptans that are commercially available in Italy (zolmitriptan 2.5 mg,
      rizatriptan 10 mg, sumatriptan 100 mg, almotriptan 12.5 mg and eletriptan 40 mg).
      The study was conducted in single-blind versus placebo and its duration was 18
      months. At the Headache Centre of the 'Agostino Gemelli' Hospital in Rome we
      selected 42 patients, suffering from headache with and without aura
      (International Headache Society Committee on Headache Classification, 1988
      Cephalalgia 8:1-96), whose headache frequency ranged between 1- and 4-monthly
      crises. For a total of 25 crises, for every five consecutive crises, a different
      triptan was taken. The end-points of the study were as follows: response at 2 h,
      'pain free' at 2 h and 'sustained pain free' (at 24 h). The intra-patient
      consistency and the tolerability were also evaluated. Thirty patients completed
      the study and the statistical analysis was only applied to these patients. No
      substantial difference in terms of the efficacy of the triptans was noted; all
      triptans were well tolerated. These results suggest the possibility of testing
      different triptans in the same patient in order to identify the ideal drug for
      every patient.

PMID- 15958098
TI  - Restricted pain and thermal sensory loss in a patient with pontine lacunar
      infarction: a clinical MRI study.
AB  - Pure sensory syndrome (PSS) is characterized by hemisensory symptoms without
      other major neurological signs. It was initially attributed to thalamic lacunar
      infarction, but several reports have shown the PSS can be due to small infarcts
      involving the posterior part of the internal capsula, the cerebral cortex and the
      brainstem. Paramedian and lateral pontine infarctions are associated respectively
      with lemniscal and spinothalmic (ST) sensory impairment. We describe a patient
      with an isolated impairment of the ST modalities caused by a segmental paramedian
      pontine infarction.

PMID- 15958099
TI  - Myasthenia gravis accompanied by alopecia areata: clinical and immunogenetic
      aspects.
AB  - The purpose of this study was to evaluate the clinical characteristics of
      patients who had both myasthenia gravis (MG) and alopecia areata (AA). Clinical
      information was retrospectively collected for 159 Japanese patients with MG.
      Human leukocyte antigen (HLA)-DQB1 and DRB1 alleles were determined by
      genotyping. Of 159 MG patients, six (3.7%) developed AA after the onset of MG and
      thymectomy. The prevalence of AA in MG patients was higher than that reported in
      Caucasians. The frequencies of bulbar involvement, myasthenic crisis, and thymoma
      were significantly higher in MG patients with AA than in those without (P =
      0.007, 0.004, and 0.006, respectively). All but one patient with AA had advanced
      stage thymoma. Three patients with a severe form of AA (alopecia totalis) had
      additional autoimmune diseases: myocarditis, myositis, and pure red cell aplasia.
      DRB1*0901 and DQB1*0303 tended to be more frequently detected in the six MG
      patients with AA than in the 82 patients without it. In conclusion, a subset of
      MG patients who have severe neuromuscular symptoms and thymoma develop AA several
      years after thymectomy.

PMID- 15958100
TI  - Anomalous vertebral artery origin may be an independent risk factor for arterial
      dissection.

PMID- 15958103
TI  - Abstracts of the Tripartite 2005 Colorectal Meeting , Dublin, Ireland, 5-7 July
      2005.

PMID- 15958104
TI  - B-type natriuretic peptides: applications for heart failure management in 2005.

PMID- 15958105
TI  - Prioritizing health-care funding: all things considered.

PMID- 15958106
TI  - Use of low-dose mitozantrone to treat aggressive multiple sclerosis: a single
      centre open-label study using patient self-assessment and clinical measures of
      multiple sclerosis status.
AB  - BACKGROUND: There is significant evidence supporting the use of mitozantrone in
      the treatment of multiple sclerosis (MS) but few data on the subtypes of MS that
      respond or which measures of disease status are most useful. AIMS: To assess the
      efficacy of low-dose (5 mg/m2 3 monthly) mitozantrone using patient self
      assessment questionnaire (SAQ), expanded disability status score (EDSS), multiple
      sclerosis functional composite score (MSFC), and the fatigue severity scale
      (FSS). Then, to compare the responses of a subgroup of relapsing remitting MS
      (RRMS) and secondary progressive MS (SPMS) patients to treatment, and to assess
      which measures of MS disease status are the most useful in a study of this type.
      METHOD: Thirty-one patients with definite (McDonald criteria) active MS were
      commenced on mitozantrone 5 mg/m2 every 3 months. EDSS, MSFC and FSS data
      collected before treatment and after 12 months were analysed. The SAQ was
      administered after at least 12 months of therapy. RESULTS: RRMS patients showed
      significantly more response to mitozantrone than SPMS patients in terms of MSFC
      (P = 0.02) and SAQ (P = 0.01). CONCLUSIONS: Low-dose mitozantrone was well
      tolerated and useful in active RRMS in the short term; however, mitozantrone did
      not display any useful activity in SPMS patients over this time interval or at
      the mitozantrone dose used. Patient perception of treatment is a worthwhile
      outcome measure and the MSFC is the most useful objective measure of MS status
      change in this type of study.

PMID- 15958107
TI  - QTc abnormalities in deliberate self-poisoning with moclobemide.
AB  - BACKGROUND: Several medications have been found to prolong the QT interval in
      overdose. This can predispose to torsade de pointes-type ventricular tachycardia.
      AIMS: To analyse the effects of moclobemide deliberate self-poisoning on the
      length of both QT and corrected QT (QTc) intervals. METHODS: Electrocardiograms
      (ECG) of all patients presenting to a regional toxicology service with
      moclobemide ingestion were reviewed. Cases where a cardiotoxic agent was
      coingested were excluded. QT and QTc parameters were compared with a comparison
      group of patients ingesting paracetamol or benzodiazepines. RESULTS: Of 75
      patients where ECG were available, the median ingested dose was 4.5 g
      (interquartile range (IQR): 2.4-7.5; range: 0.6-18 g) and the median age was 34
      years (IQR: 26-44). The mean QT interval was 415 ms (standard deviation (SD): 51
      ms) with a mean QTc of 459 ms (SD: 44 ms), and were prolonged compared with the
      comparison group. Twelve female patients had a QTc > 500 ms and in seven of these
      causality was established based on a pre- or post-ECG with a QTc < 500 ms. Only
      10% of the moclobemide cases had a heart rate (HR) > 100 beats per minute, making
      overcorrection of HR by Bazett's formula an unlikely cause of the findings. No
      cardiac arrythmias were observed other than one case of first-degree heart block.
      CONCLUSIONS: Moclobemide prolongs the QT and QTc intervals in overdose and a 12
      lead ECG should be done on all moclobemide deliberate self-poisonings. Continuous
      cardiac monitoring for what is otherwise a relatively benign overdose would
      appear to be an inappropriate use of resources but can be considered in patients
      with a QTc > 500 ms or with known risks for QT prolongation.

PMID- 15958108
TI  - Mediastinal adenopathy: finding the answer with endoscopic ultrasound-guided fine
      needle aspiration biopsy.
AB  - BACKGROUND: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS FNA)
      is a relatively new imaging modality that has been reported to be useful for
      mediastinal nodal staging of lung cancer and for the evaluation of mediastinal
      adenopathy of unknown cause. However, the technique is not commonly used in
      Australia. METHODS: A retrospective review of all patients who had mediastinal
      EUS FNA was undertaken. Of a total of 787 patients who had undergone endoscopic
      ultrasound (EUS) studies from November 1999 to March 2004, 27 patients were
      identified to have had mediastinal EUS FNA. Details were recorded including study
      indication, history of malignancy, source of referral, prior attempts for tissue
      diagnosis, EUS and EUS FNA findings, complications, surgical pathology if
      available and clinical outcome after diagnosis. RESULTS: Mediastinal EUS FNA was
      performed on an outpatient basis and no complications were recorded. Diagnostic
      material was obtained from all patients with a mean number of three passes. Nodal
      stations sampled included left paratracheal, subcarinal, aortopulmonary window
      and inferior mediastinum. Indications for the studies included mediastinal
      adenopathy of uncertain cause (17), lung cancer staging (7) and gastrointestinal
      cancer staging (3). EUS FNA confirmed malignancy in 16/27 patients, sarcoidosis
      in three patients, tuberculosis in one patient and seven patients were deemed to
      have reactive adenopathy. Primary cytopathological diagnosis of malignancy was
      determined by EUS FNA in nine patients. CONCLUSIONS: EUS FNA is a safe, efficient
      and effective modality for mediastinal staging of lung cancer and for the
      diagnosis of mediastinal adenopathy of uncertain origin. EUS FNA has the
      potential to significantly impact on patient management, avoiding more invasive
      procedures as well as unnecessary operations.

PMID- 15958109
TI  - Use of point-of-care online clinical evidence by junior and senior doctors in New
      South Wales public hospitals.
AB  - BACKGROUND: The Clinical Information Access Program (CIAP), an online evidence
      retrieval system, provides NSW health professionals in public hospitals with 24 h
      access to information supporting evidence-based practice. AIM: To assess the
      frequency and type of CIAP usage by senior and junior medical staff and doctors'
      attitudes to CIAP. METHODS: A convenience sample of 25% of doctors from 65
      randomly selected public hospitals completed a survey. Junior (n = 392) and
      senior (n = 684) doctors' responses were compared using chi2 analyses and t
      tests. RESULTS: Most doctors had heard of CIAP (71.8%) and 60.6% had used it.
      More junior (72.4%) than senior (53.8%) doctors had used CIAP and junior doctors
      found it easier to use. Of the users 93.5% believed CIAP had the potential to
      improve patient care; 55.2% had directly experienced this. Most usage (61.5%)
      occurred at point-of-care; 74% of users found all/most of the information they
      sought and 71.6% found the search time to be 'good/excellent'. Users had
      increased their usage in the past year and predicted increased future usage. The
      most popular databases were Medline and MIMS. Age, access to other evidence, and
      lack of training, time and computer skills were associated with non-usage. Junior
      and senior users differed in 4 of 15 reasons for using CIAP. CONCLUSIONS: CIAP is
      used and valued by the majority of doctors. Patterns of usage, online experiences
      and the attitudes toward CIAP of senior doctors who use CIAP are relatively
      similar to those of junior doctors.

PMID- 15958110
TI  - Phase II study of prolonged ambulatory infusion carboplatin and oral etoposide
      for patients progressing through hormonal therapy for prostate cancer.
AB  - AIM: To develop a well-tolerated outpatient chemotherapy regimen for hormone
      insensitive prostate cancer. METHOD: Forty patients received carboplatin 20 mg/m2
      by continuous ambulatory infusion with oral etoposide 50 mg/day for 21 days
      repeated every 6 weeks. RESULTS: Four patients had a partial response and 16
      patients had stable disease. Two of the partial responders and three additional
      patients recorded falls in prostate specific antigen of 50% or more. The median
      freedom from progression was 24 weeks and median survival 32 weeks. Twenty-four
      of 31 patients had decreasing pain scores and 20 of 34 patients recorded improved
      quality of life with at least one cycle of treatment. The main toxicity occurred
      in seven patients with World Health Organization (WHO) grade 4 neutropenia and in
      four patients with WHO grade 3 neutropenia. Only one patient developed febrile
      neutropenia. Six patients had grade 3 anaemia and three patients had grade 3
      thrombocytopenia. Two patients reported grade 3 lethargy whereas 11 patients had
      grade 2 lethargy. CONCLUSION: This was a well-tolerated regimen that improved
      symptomatic control of hormone-insensitive prostate cancer.

PMID- 15958111
TI  - Prioritizing health-care funding.
AB  - In the face of limited resources, on what basis should we prioritize health-care
      funding? The most influential consideration should be the knowledge that an
      intervention does something beneficial for the person who receives it. Rather
      than using imposed knowledge or knowledge obtained by grace, modern medicine uses
      knowledge obtained by rational thought. Traditionally, two philosophical schools
      of rational thought support medical interventions: empiricism and rationalism.
      Empiricist knowledge underpins the treatment of risk, while rationalist knowledge
      underpins the treatment of disease. To introduce reasoned order into the
      rationing process we must understand the limitations inherent in the application
      of these two forms of knowledge. Why are screening programmes for breast and
      uterine cervical cancer supported while severe restrictions are placed on
      treatments for chronic arthritis? Can the benefits of cholesterol-lowering drugs
      be measured? Empiricism has achieved an unchallenged ascendancy in modern health
      care delivery. Is this ascendancy justified? There is a need for reference
      criteria to compare the benefits of competing interventions across disciplines.
      As a starting point for debate we propose that interventions should be given a
      priority based on how closely they fulfil five criteria: knowledge of disease
      pathophysiology, measurability of short-term and long-term benefits, incidence of
      serious adverse effects and affordability. It is only by using and refining such
      funding criteria that better public understanding of the rationing process will
      be achieved and political interference minimized.

PMID- 15958112
TI  - Recognition and optimal management of schizophrenia and related psychoses.
AB  - Schizophrenia continues to remain one of the major unsolved conditions of our
      time, contributing significantly to causes of disability worldwide. Advances in
      neuroimaging have demonstrated that schizophrenia appears to be primarily a
      neurodevelopmental disorder. The dopamine theory of schizophrenia continues to
      hold sway but interest is growing in the role of other neurotransmitters. Genetic
      linkage studies continue to suggest that specific chromosomes have a role in the
      aetiology of the condition but the findings are, as yet, inconsistent. A new
      generation of drug therapies and reforms of the mental health system have meant
      that it is now possible to treat the majority of those with this condition in the
      community albeit, in some instances, against their will. The medical
      complications of both the disorder, the lifestyle changes resulting from the
      disorder and the new and older medications have come to prominence in recent
      years. The development of guidelines for treatment has the potential to reduce
      the variability in clinical practice that currently exists in the management of
      the condition.

PMID- 15958113
TI  - New therapeutic target in inflammatory disease: macrophage migration inhibitory
      factor.
AB  - The cytokine macrophage migration inhibitory factor (MIF) participates in
      fundamental events in innate and adaptive immunity. The profile of activities of
      MIF in vivo and in vitro is strongly suggestive of a role for MIF in the
      pathogenesis of many inflammatory diseases, including rheumatoid arthritis (RA),
      and hence antagonism of MIF is suggested as a potential therapeutic strategy in
      inflammatory disease. The best developed case for therapeutic antagonism of MIF
      is in RA. In RA, MIF is abundantly expressed in serum and synovial tissue. MIF
      induces synovial expression of key pro-inflammatory genes, regulates the function
      of endothelial cells and leucocytes, and is implicated in the control of
      synoviocyte proliferation and apoptosis via direct effects on the expression of
      the tumour suppressor protein p53. In animal models of RA, anti-MIF antibodies or
      genetic MIF deficiency are associated with significant inhibition of disease. A
      similar case has been made, for example using MIF-deficient mice, in models of
      atheroma, colitis, multiple sclerosis and other inflammatory diseases. The
      relationship with p53 also means MIF may be important in the link between
      inflammatory disease and cancer, such as is seen in RA or colitis. MIF also has a
      unique relationship with glucocorticoids, in that despite antagonizing their
      effects, the expression of MIF is in fact induced by glucocorticoids. Thus, MIF
      functions as a physiological counter-regulator of the anti-inflammatory effects
      of glucocorticoids. This may be entrained by selective activation of mitogen
      activated protein kinases rather than nuclear factor kappa B. Therapeutic MIF
      antagonism may therefore provide a specific means of 'steroid sparing'.
      Exploitation of antibody, soluble receptor or small molecule technologies may
      soon lead to the ability to test in the clinic the importance of MIF in human
      inflammatory diseases.

PMID- 15958114
TI  - Technology, embodiment and abortion.

PMID- 15958115
TI  - Cerebral abscess with pneumocephalus.

PMID- 15958116
TI  - Part I. General practitioner-specialist relationship.
AB  - This article is the first of a two-part series that seeks to explore the
      relationship and interaction between general practitioners (GPs) and medical
      specialists. A historical account of the medical profession is given, beginning
      from the tripartite division (i.e. the physicians, surgeons or barbers and the
      apothecaries), the Apothecaries Act of 1815, and the Medical Act of 1858. An
      account is also given of factors that exacerbated the division and friction
      between GPs and specialists, and how general practice developed in Australia. The
      role of the GP is stated as the provision of primary care, preventive care,
      patient-centred care, continuing care, comprehensive care, and community-based
      care to individuals and their families. The role of the specialists on the other
      hand is that of a consultant to advise GPs who carry on the management after the
      patient leaves the specialist. The dynamics of the GP-specialist relationship are
      discussed in relation to power, interdependence, morale, public image, education
      and training, and support from the Colleges, and we conclude by discussing the
      importance of collaboration between professions.

PMID- 15958117
TI  - Transient global amnesia following coronary angiography and angioplasty.

PMID- 15958118
TI  - 'Grape-sultana' sign represents a favourable response to aggressive treatment of
      early diffuse systemic scleroderma.

PMID- 15958119
TI  - Tuberculosis and abdominal pain.

PMID- 15958120
TI  - From Bolam to Ipp.

PMID- 15958123
TI  - The immunobiology of Guillain-Barre syndromes.
AB  - This presentation highlights aspects of the immunobiology of the Guillain-Barre
      syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular
      paralysis. Understanding the key pathophysiological pathways of GBS and
      developing rational, specific immunotherapies are essential steps towards
      improving the clinical outcome of this devastating disorder. Much of the research
      into GBS over the last decade has focused on the forms mediated by anti
      ganglioside antibodies, and we have made substantial progress in our
      understanding in several related areas. Particular highlights include (a) the
      emerging correlations between anti-ganglioside antibodies and specific clinical
      phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor
      axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome;
      (b) the identification of molecular mimicry between GBS-associated Campylobacter
      jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for
      anti-ganglioside antibody induction; (c) the development of rodent models of GBS
      with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1
      gangliosides, respectively. Our work has particularly studied the motor nerve
      terminal as a model site of injury, and through combined active and passive
      immunisation paradigms, we have developed murine neuropathy phenotypes mediated
      by anti-ganglioside antibodies. This has been achieved through use of
      glycosyltransferase and complement regulator knock-out mice, both for cloning
      anti-ganglioside antibodies and inducing disease. Through such studies, we have
      proven a neuropathogenic role for murine anti-ganglioside antibodies and human
      GBS-associated antisera and identified several determinants that influence
      disease expression including (a) the level of immunological tolerance to
      microbial glycans that mimic self-gangliosides; (b) the ganglioside density in
      target tissue; (c) the level of complement activation and the neuroprotective
      effects of endogenous complement regulators; and (d) the role of calcium influx
      through complement pores in mediating axonal injury. Such studies provide us with
      clear information on an antibody-mediated pathogenesis model for GBS and should
      lead to rational therapeutic testing of agents that are potentially suitable for
      use in humans.

PMID- 15958124
TI  - Treatment of Guillain-Barre syndrome and CIDP.
AB  - Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating poly
      (radiculo)neuropathy (CIDP) are immune-mediated disorders with a variable
      duration of progression and a range in severity of weakness. Infections can
      trigger GBS and exacerbate CIDP. Anti-ganglioside antibodies are important, but
      there is debate on the role of genetic factors in the pathogenesis of these
      disorders. Randomized controlled trials (RCT) have shown that intravenous
      immunoglobulin (IVIg) and plasma exchange (PE) are effective in both GBS and
      CIDP. Most CIDP patients also improve after steroid therapy. Despite current
      treatment options, many patients have residual deficits or need to be treated for
      a long period of time. Therefore, new treatment trials are highly indicated. This
      review focuses on the current and possible new treatment options that could be
      guided by recent results from laboratory experiments.

PMID- 15958125
TI  - Laminins and their receptors in Schwann cells and hereditary neuropathies.
AB  - This review focuses on the influence of laminins, mediated through laminin
      receptors present on Schwann cells, on peripheral nerve development and
      pathology. Laminins influence multiple aspects of cell differentiation and tissue
      morphogenesis, including cell survival, proliferation, cytoskeletal
      rearrangements, and polarity. Peripheral nerves are no exception, as shown by the
      discovery that defective laminin signals contribute to the pathogenesis of
      diverse neuropathies such as merosin-deficient congenital muscular dystrophy and
      Charcot-Marie-Tooth 4F, neurofibromatosis, and leprosy. In the last 5 years,
      advanced molecular and cell biological techniques and conditional mutagenesis in
      mice began revealing the role of different laminins and receptors in developing
      nerves. In this way, we are starting to explain morphological and pathological
      observations beginning at the start of the last century. Here, we review these
      recent advances and show how the roles of laminins and their receptors are
      surprisingly varied in both time and place.

PMID- 15958126
TI  - Impaired peripheral nerve regeneration in diabetes mellitus.
AB  - Diabetes mellitus impairs peripheral nerve regeneration. Regenerative failure
      likely exacerbates deficits from polyneuropathy or focal neuropathies in patients
      who might otherwise exhibit spontaneous improvement. Some focal neuropathies,
      like carpal tunnel syndrome, are common, yet render ongoing disability because of
      their delayed recovery. Why diabetic nerves fail to regenerate is an interesting
      question to consider because several mechanisms likely contribute. In this
      review, we examine a number of these causes. These causes include microangiopathy
      or disease of small blood vessels, failure to provide proper metabolic support
      for repair, defects in the entry and actions of inflammatory cells within the
      injury milieu, less robust support of axons by their Schwann cells, and lack of a
      full repertoire of trophic factors. A number of the mechanisms that generate
      neuropathy in the first place also likely contribute to failed regenerative
      programs, but how they do so is not clear.

PMID- 15958127
TI  - History of standard scoring, notation, and summation of neuromuscular signs. A
      current survey and recommendation.
AB  - In this article, we trace the history of scoring, notation, and summation of the
      neuromuscular signs of muscle weakness and decrease of tendon reflexes and
      sensation. We recommend a standard system to promote consistency in the effort
      introduced by Mitchell and Lewis to "represent systems and force by their signs."
      The scoring of neuromuscular signs began with Mitchell and Lewis in the 19th
      century who used pluses, minuses, and N (for normal) to express the activity of
      muscle stretch reflexes. Henry Plummer introduced an ordinal scoring approach for
      muscle weakness, reflex decrease and increase, and sensation loss. In 1919, he
      and Walter Sheldon and Henry Woltman introduced standard pre-printed examination
      forms with written instructions for notation and scoring. Robert Lovett, a Boston
      orthopedist, scored weak muscles of poliomyelitis patients from 2 (mild weakness)
      to 6 (paralyzed), 1 being normal. Lovett's approach was used, after reversing the
      order of the grades and decreasing each grade by 1, by a Committee of the Medical
      Research Council for evaluating return of muscle weakness after nerve injury.
      Despite dissimilarity to existing reflex and sensation scores and uneven width of
      grades, this approach was widely adopted for use in neurologic practice. We
      introduced the Neuropathy Impairment Score using a combination of the Mitchell,
      Plummer, and Lovett approaches, summing all individual scores of a standard set
      of neuromuscular examinations. In a non-representative survey of 19 neuromuscular
      physicians from different countries, we find that there is a considerable
      variability in the approaches used for grading. Assuming that scoring is useful,
      we herein suggest (a) impairments should be scored separately from hyperfunction
      and (b) for the scoring of impairments (muscle weakness, reflex decrease, and
      sensation loss), the same ordinal scoring approach should be used with 0 as
      normal and 1, 2, ... representing increasing impairment based on the judgment of
      percentage abnormality with corrections made for age, sex, physical fitness, and
      physical characteristics.

PMID- 15958128
TI  - Antibodies to peripheral nerve myelin proteins in chronic inflammatory
      demyelinating polyradiculoneuropathy.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired
      disorder of the peripheral nervous system with a probable auto-immune
      pathogenesis. The nature of the responsible autoantigens is unclear in most
      patients. We used the Western immunoblot technique to seek antibodies to
      peripheral nerve protein antigens. Sera from eight of 32 (25%) CIDP patients, 12
      of 37 (32%) Guillain-Barre syndrome (GBS) patients, zero of 30 (0%) chronic
      idiopathic axonal polyneuropathy patients and two of 39 (5%) healthy control
      subjects contained anti-peripheral nerve protein antibodies. The frequency of
      such antibodies was significantly greater in both CIDP (p = 0.04) and GBS (p =
      0.003) patients than in normal control subjects. For CIDP patients, there were
      non-significant trends for antibodies to be more common in females and in those
      who responded to treatment with either intravenous immunoglobulin or plasma
      exchange. The commonest antibodies were directed against a band at 28 kDa,
      resembling that labelled by a monoclonal antibody against myelin protein zero
      (P0). Six CIDP and seven GBS patients' sera reacted with this band. These results
      support the view that antibodies to myelin proteins, and especially P0, are
      present in the serum of some patients with CIDP and GBS.

PMID- 15958129
TI  - Functional health status of patients with chronic inflammatory neuropathies.
AB  - The functioning of 12 patients with chronic inflammatory demyelinating
      polyneuropathy (CIDP) and 18 patients with multifocal motor neuropathy (MMN) was
      evaluated to obtain health profiles and appropriate clinimetric instruments.
      Assessment was made in a cross-sectional study by means of a performance-based
      body function test (hand-held dynamometry), two performance-based activity tests
      (10-m walk test and Berg balance scale), a self-reported activity test (Canadian
      Occupational Performance Measure), and a self-reported functioning test (sickness
      impact profile 68). In both patient groups, CIDP and MMN, specific health
      profiles were manifest. A clear relationship between body function, activities,
      and functioning was not found. Therefore, to assess a patient with inflammatory
      neuropathy, it is recommended to assess body function as well as activities and
      functioning and to select appropriate clinimetric instruments specific for each
      type of neuropathy.

PMID- 15958130
TI  - Harmful effects of anti-GalNAc-GD1a antibodies and TNF-alpha on rat dorsal root
      ganglia.
AB  - The clinical characteristics of five (22%) of 23 patients with Guillain-Barre
      syndrome (GBS), whose serum contained immunoglobulin G (IgG) antibodies to the
      ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a), included pure motor
      weakness of the axonal type. These patients had a relatively good prognosis, but
      displayed higher serum tumor necrosis factor-alpha (TNF-alpha) titers than the
      other GBS patients. We examined the effect of serum from these patients with IgG
      anti-GalNAc-GD1a antibodies on neurites from cultured rat dorsal root ganglia
      (DRG) and found it to damage the myelin in well-elongated DRG neurites and
      monolayer cultures of Schwann cells and neurons. In the regeneration model, serum
      from these patients delayed neurite extension and inhibited Schwann cell
      proliferation. Neurons in cultured monolayers showed vacuolation and decreased
      rapidly in number. Schwann cells were also vacuolated and readily detached from
      the substratum. The effects of IgG anti-GalNAc-GD1a antibodies purified from one
      of the patients, rabbit serum after immunization with GalNAc-GD1a, and
      recombinant TNF-alpha were also examined. IgG anti-GalNAc-GD1a antibodies mainly
      inhibited the regeneration and preservation of neurons, while TNF-alpha mainly
      induced morphological changes in well-proliferated Schwann cells and myelin.

PMID- 15958132
TI  - Archived digital images of sensory receptors.

PMID- 15958131
TI  - Intraepidermal nerve fiber density in rat foot pad: neuropathologic
      neurophysiologic correlation.
AB  - Quantification of cutaneous innervation in rat footpad is a useful tool to
      investigate sensory small-diameter nerve fibers, which are affected early in
      peripheral neuropathies. The aim of this work was to provide normative reference
      data on the density of intraepidermal nerve fibers (IENFs) and Langerhans cells
      in the hindpaw footpad of Sprague-Dawley and Wistar rats. We also evaluated the
      sensibility of IENF density by comparing neuropathologic findings with
      neurophysiologic examination and the presence of peripheral neuropathy in two
      well-characterized animal models of neuropathy. IENF density was quantified in 22
      Sprague-Dawley rats and 13 Wistar rats and compared with 19 age-matched Sprague
      Dawley rats with streptozotocin-induced diabetic neuropathy and 30 age-matched
      Wistar rats with cisplatin- or paclitaxel-induced neuropathy. Antidromic tail
      sensory nerve conduction velocity (SNCV) was assessed in all animals. IENF and
      Langerhans cell densities were constant in healthy Sprague-Dawley rats at any
      age, and they were similar to those observed in healthy Wistar rats. In
      neuropathic rats, both SNCV and IENF density were significantly reduced with
      respect to controls. Quantification of IENF density was significantly correlated
      with changes in conduction velocity. Diabetic neuropathy rats alone showed a
      significantly higher density of Langerhans cells compared with controls. Our
      study demonstrated that IENF density quantification correlates with SNCV changes
      and suggests that this might represent a useful outcome measurement in
      experimental neuropathies.

PMID- 15958133
TI  - Acute motor axonal neuropathy in a Turner's syndrome patient with a "potential"
      celiac disease.

PMID- 15958134
TI  - Appraising mouse nerve: dessication artifact.

PMID- 15958135
TI  - Combined hereditary neuropathy with liability to pressure palsy and non-systemic
      vasculitic neuropathy.

PMID- 15958136
TI  - Sources of openness/intellect: cognitive and neuropsychological correlates of the
      fifth factor of personality.
AB  - We characterize Openness/Intellect as motivated cognitive flexibility, or
      cognitive exploration, and develop a neuropsychological model relating it to
      dopaminergic function and to the functions of the prefrontal cortex (PFC).
      Evidence is reviewed for sources of Openness/Intellect shared with Extraversion
      and sources unique to Openness/Intellect. The hypothesis that the cognitive
      functions of the dorsolateral PFC are among the latter was tested using standard
      measures of cognitive ability and a battery of tasks associated with dorsolateral
      PFC function (N=175). Dorsolateral PFC function, as well as both fluid and
      crystallized cognitive ability, was positively related to Openness/Intellect but
      no other personality trait. Additionally, facet level analysis supported the
      characterization of Openness/Intellect as a primarily cognitive trait.

PMID- 15958137
TI  - Cognitive processes underlying coping flexibility: differentiation and
      integration.
AB  - This study investigates how individuals formulate flexible coping strategies
      across situations by proposing differentiation and integration as two stress
      appraisal processes. Results showed that participants who coped more flexibly
      adopted the dimensions of controllability and impact in differentiating among
      different stressful situations. They also deployed an integrated strategy: the
      deployment of more monitoring in situations perceived as controllable but less of
      this strategy in situations perceived as uncontrollable. Participants who coped
      less flexibly did not adopt any given dimensions and tended to use more
      monitoring regardless of situational characteristics. These results suggest that
      individuals with different extents of coping flexibility differ in the cognitive
      processes. Individuals who cope more flexibly display a greater extent of
      differentiation and integration than do those who cope less flexibly. These
      findings are translated into strategies for stress management workshops.

PMID- 15958138
TI  - Aggression and self-esteem: a diary study of children's reactivity to negative
      interpersonal events.
AB  - The study employs a daily diary design to assess self-esteem reactivity and its
      association with children's aggressive behavior. We test the hypothesis that the
      self-esteem of aggressive children will be more reactive to negative
      interpersonal events than the self-esteem of nonaggressive children. Results
      provide partial support for the aggression/reactivity hypothesis. Aggressive
      children's self-esteem was more reactive to negative peer events but less
      reactive to negative adult events than the self-esteem of less aggressive
      children. These findings are discussed in relation to the experimental literature
      relating self-esteem instability and ego-threat to aggression and in relation to
      the extensive body of research on childhood aggression. Intervention implications
      are also considered.

PMID- 15958139
TI  - Personality correlates of heroic rescue during the holocaust.
AB  - This study investigated the extent to which personality variables can be used to
      discriminate non-Jewish heroes of the Holocaust from bystanders and from a
      comparison group of prewar European immigrants who left their countries of origin
      prior to World War II. Eighty verified rescuers, 73 bystanders, and 43 immigrants
      were administered measures of locus of control, autonomy, risk taking, social
      responsibility, tolerance/authoritarianism, empathy, and altruistic moral
      reasoning. A three-group discriminant function analysis was able to correctly
      classify 80.2% of the sample by a combination of personality and demographic
      variables. When the bystanders and immigrants, who differed very little from each
      other, were grouped together and compared to the rescuers, the personality
      variables alone correctly classified 93.1% of the sample. Implications regarding
      the relationship between personality and altruistic behavior, as well as
      suggestions for future research are discussed.

PMID- 15958140
TI  - When opposites attract: a multi-sample demonstration of complementary person-team
      fit on extraversion.
AB  - This study assessed the nature of the person-team fit relationships for
      extraversion on members' attraction toward their teams. Unlike most studies of
      personality-based fit, which emphasize similarity, we predicted that
      complementary fit on extraversion (i.e., high individual-low team or low
      individual-high team levels) would result in greater attraction to the team. Data
      from two independent samples of intact project teams were analyzed, including 324
      MBA students comprising 64 case analysis teams and 217 members of 26
      manufacturing teams. Using polynomial regression analysis and three-dimensional
      surface plots, our results supported the predicted relationship. In addition, the
      data indicated that individuals who were more attracted to their teams were also
      better performers, as judged by their peers and supervisors.

PMID- 15958141
TI  - Who are the people reluctant to participate in research? Personality correlates
      of four different types of nonresponse as inferred from self- and observer
      ratings.
AB  - This article outlines a typology of nonresponse biases that may occur in research
      based on voluntary participation and presents empirical evidence on the
      relationships between nonresponse and personality traits. We describe four
      different types of nonresponse occurring at the recruitment stage, during data
      collection, and at the stage of recruitment for further research. Personality
      correlates of all types of nonresponse were investigated using data from an
      online survey e-mailed to owners of personal Web sites, and observer ratings on
      the targets' personality were obtained. After reviewing the target persons' Web
      sites, observers judged complete nonrespondents as less agreeable and less open
      to experience than respondents. Furthermore, higher extraversion, higher openness
      to experience, and higher narcissism differentiated volunteers for follow-up
      research from nonvolunteers in both self- and observer ratings. We found only
      weak evidence of personality correlates of careless and selective item
      nonresponse. Findings show that nonresponse biases may have significant
      implications for representativeness in surveys and personality test norms.

PMID- 15958142
TI  - Existential meaning's role in the enhancement of hope and prevention of
      depressive symptoms.
AB  - The authors confirmed that existential meaning has a unique relationship with and
      can prospectively predict levels of hope and depressive symptoms within a
      population of college students. Baseline measures of explicit meaning (i.e., an
      individual's self-reported experience of a sense of coherence and purpose in
      life) and implicit meaning (i.e., an individual's self-reported embodiment of the
      factors that are normatively viewed as comprising a meaningful life) explained
      significant amounts of variance in hope and depressive symptoms 2 months later
      beyond the variance explained by baseline levels of hope/depression, neuroticism,
      conscientiousness, agreeableness, openness to experience, extraversion, and
      social desirability. The authors discuss implications of these findings for the
      field of mental health treatment and suggest ways of influencing individuals'
      experience of existential meaning.

PMID- 15958143
TI  - Bicultural identity integration (BII): components and psychosocial antecedents.
AB  - The present study examines the underresearched topic of bicultural identity;
      specifically, we: (1) unpack the construct of Bicultural Identity Integration
      (BII), or the degree to which a bicultural individual perceives his/her two
      cultural identities as "compatible" versus "oppositional," and (2) identify the
      personality (Big Five) and acculturation (acculturation stress, acculturation
      attitudes, bicultural competence) predictors of BII. Differences in BII,
      acculturation stress, and bicultural competence were measured with new
      instruments developed for the purposes of the study. Using a sample of Chinese
      American biculturals, we found that variations in BII do not define a uniform
      phenomenon, as commonly implied in the literature, but instead encompass two
      separate independent constructs: perceptions of distance (vs. overlap) and
      perceptions of conflict (vs. harmony) between one's two cultural identities or
      orientations. Results also indicated that cultural conflict and cultural distance
      have distinct personality, acculturation, and sociodemographic antecedents.

PMID- 15958144
TI  - Inattentive listening undermines self-verification in personal storytelling.
AB  - Two studies explore the narrative construction of self-perceptions in
      conversational storytelling among pairs of same-sex friends. Specifically, the
      studies examined how listener behavior can support or undermine attempts to self
      verify in personal storytelling. In two studies (n=100 dyads), speakers told
      attentive, distracted, or disagreeable (Study 1 only) friends about a recent
      experience. Distracted, but not disagreeable, friends tended to undermine
      participants' attempts to verify their self-perception of being interested in an
      activity (Study 1) or their self-perception that an event was typical for them
      (Study 2). These results support the notion that friends can be an important
      source of influence on self-perceptions and, perhaps surprisingly, suggest that
      responsiveness from friends, rather than agreement per se, may be crucial for
      supporting self-verification processes.

PMID- 15958145
TI  - Processing of facial expressions of negative emotion in alexithymia: the
      influence of temporal constraint.
AB  - Alexithymia, a characteristic involving a limited affective vocabulary appears to
      involve three components: difficulty identifying feelings, difficulty describing
      feelings, and externally oriented thinking. There is evidence that alexithymic
      characteristics are associated with differences in emotion information
      processing. We examined the role of temporal factors in alexithymic emotion
      processing deficits, taking into account the confound between alexithymic
      characteristics and positive and negative affectivity. One hundred forty-six
      participants completed the 20-item Toronto Alexithymia Scale and the Positive and
      Negative Affect Schedule. In a signal-detection paradigm, participants judged
      facial expressions depicting neutral or negative emotions under slow and rapid
      presentation conditions. The alexithymia component of difficulty in describing
      feelings was inversely related to the ability to detect expressions of negative
      emotion in the speeded condition. This relationship was independent of positive
      and negative affectivity. Alexithymic components positive and negative
      affectivity were unrelated to response bias. The results emphasize the influence
      of difficulty describing feelings within the alexithymia construct and its
      difference from positive and negative affectivity. They suggest that an
      alexithymic deficit in describing feelings is associated with a deficit in
      processing negative emotions that is most apparent when processing capacity is
      challenged. Theoretical and methodological implications are discussed.

PMID- 15958146
TI  - Safe motherhood in Jamaica: from slavery to self-determination.
AB  - The development of maternal health care in Jamaica is reviewed by examining
      government documents and publications to identify social and political factors
      associated with maternal mortality decline. Modern maternity services began with
      the 1887 establishment of the Victoria Jubilee Hospital and Midwifery School.
      Community midwives were deployed widely by the 1930s and community antenatal care
      expanded in the 1950s. Social policies in the 1970s increased women's access to
      primary health care, education and social support; improved transportation in the
      1990s facilitated hospital delivery. Maternal mortality declined rapidly from
      approximately 600/100 000 in the 1930s to 200/100 000 in 1960, led by a 69%
      decline in sepsis by 1950, and a 72% decline from all causes thereafter, settling
      at approximately 100/100 000 in the 1980s. Skilled birth attendant deliveries
      moved from 39% in 1950 to 95% in 2001 and hospital births from 31% in 1960 to 91%
      in 2001. Maternal mortality plateaued at 70-80% prevalence of skilled delivery
      care. Deployment of midwives into rural communities and social development
      focused on women and children were associated with the observed improvements.
      Further reductions will require greater attention to the quality of emergency
      obstetric care.

PMID- 15958149
TI  - The search for genenotype/phenotype associations and the phenome scan.
AB  - All the approaches to the search for genotype/phenotype associations have their
      share of problems. Comparing the genome scan and candidate gene approaches, the
      former makes fewer assumptions at the genetic level or about mechanism but has
      greater statistical difficulties while the latter partially solves the
      statistical problem but makes more assumptions at both genetic and mechanistic
      levels. Among current difficulties is a lack of information about the nature of
      gene variant/phenotype associations: the frequency with which different classes
      of gene or sequence are involved; the type of genetic variation most commonly
      involved; the appropriate genetic models to apply to analysis. The overarching
      problem is that of multiple testing, one solution to which is to integrate
      genetic information to create a smaller number of compound variables. At the
      other end of the scale, decisions about the level of complexity at which to pitch
      the identification of phenotypes also affect the multiple testing problem:
      whether to pitch them at the level of disease outcomes, or at any of the multiple
      levels of intermediate phenotypes or traits. The third issue is how best to deal
      with gene/gene or gene/environment interactions, or whether to ignore them. Only
      as more genotype/phenotype associations emerge, by whatever means, will the
      numbers of results allow these questions to be answered. We describe here a new
      approach to genotype/phenotype association studies, the phenome scan, in which
      dense phenotypic information in human cohorts is scanned for associations with
      individual genetic variants. We believe that this approach can generate data that
      will be useful in answering generic questions about genotype/phenotype
      associations as well as in discovering novel ones.

PMID- 15958150
TI  - Predictors of vaginal bleeding during the first two trimesters of pregnancy.
AB  - This study evaluates maternal age, race, cigarette smoking, prior spontaneous
      abortion, prior induced abortion, and prior preterm birth in relation to vaginal
      bleeding during the first two trimesters of pregnancy. Information on vaginal
      bleeding and predictors came from the Pregnancy, Infection, and Nutrition Study,
      which enrolled 2806 pregnant women at 24-29 weeks' gestation during 1995-2000 in
      central North Carolina, USA. Generalised estimating equations were applied to
      take into account repeated episodes of vaginal bleeding during pregnancy. Women
      with advanced maternal age and passive smoking exposure were more likely to
      experience more intense vaginal bleeding during pregnancy, as were women with
      prior preterm birth. More intense bleeding was also more likely to be reported
      among women with multiple prior spontaneous abortions or multiple prior induced
      abortions, but not among women with a single prior spontaneous or induced
      abortion. The combination of prior spontaneous and induced abortion showed a dose
      response association with the occurrence of vaginal bleeding during pregnancy.

PMID- 15958151
TI  - The effect of terminations of pregnancy for fetal abnormalities on trends in
      mortality to one year of age in Western Australia.
AB  - Summary highlighted the contribution of birth defects. Over this time there has
      also been an increasing number of terminations of pregnancy for fetal
      abnormality. However, the effect of these terminations on mortality rates in
      Australia has not yet been estimated. The Western Australian Birth Defects
      Registry (BDR) records all birth defects that are diagnosed in stillbirths,
      livebirths and in pregnancies terminated because of a fetal abnormality. All
      cases on the BDR over the period 1980-98 were categorised into one of eight main
      birth defect groups and analysed in four time periods to show trends. Linkage
      provided information on deaths to one year of age, defined as perinatal plus
      postneonatal deaths. The proportion of terminations for fetal abnormality that
      would have resulted in a death before one year of age was estimated in two ways.
      The first method used the proportion of births with a birth defect in each
      diagnostic category that resulted in a death. The second method involved
      determination of likelihood of survival to one year of all terminations for fetal
      abnormality through independent review by two experts. Whilst mortality to one
      year of age for all birth defects has declined from 4.36/1000 births in 1980-84
      to 2.75/1000 births in 1995-98, terminations of pregnancies for fetal
      abnormalities increased from 1.19/1000 births to 4.70/1000 births. After
      including the estimated mortality associated with terminations for fetal
      abnormality, the decline in mortality to one year of age associated with birth
      defects from 1980 to 1998 changed from a 37% reduction to a 15% reduction based
      on observed mortality 1980-84, and an 11% increase in mortality based on
      individual case review, highlighting the importance of considering terminations
      in mortality analyses.

PMID- 15958152
TI  - Maternal body composition, offspring blood pressure and the hypothalamic
      pituitary-adrenal axis.
AB  - We tested the hypothesis that women who are thin or have poor pregnancy weight
      gain have offspring with higher blood pressure and examined whether this link is
      mediated by increased secretion of cortisol. We studied a cohort of 388 children
      born in Kingston, Jamaica. From hospital records we obtained information about
      their mother's body mass index (BMI) and weight gain during pregnancy. At age 8.5
      years we measured the children's fasting plasma cortisol concentrations and blood
      pressure and assessed their mother's anthropometry. There were no relationships
      between the mother's BMI or weight gain during pregnancy and offspring blood
      pressure. However, mothers with a greater subscapular to triceps skinfold
      thickness ratio (SSTR) had offspring with higher blood pressure (5.6 mmHg
      systolic and 3.7 mmHg diastolic increase per unit change in SSTR, P = 0.002 and P
      = 0.008 respectively). Fasting plasma cortisol concentrations correlated with the
      children's systolic (r = 0.33, P < 0.0001) and diastolic pressures (r = 0.12, P =
      0.02) independently of age, gender, weight or socio-economic status and were also
      predicted by the mother's SSTR. These findings suggest that maternal truncal
      obesity rather than thinness is associated with raised blood pressure in the
      offspring, and that this link may be mediated by increased cortisol secretion.

PMID- 15958153
TI  - Multilingual home environment and specific language impairment: a case-control
      study in Chinese children.
AB  - Specific language impairment (SLI) is a common developmental disorder in young
      children. To investigate the association between multilingual home environment
      and SLI, we conducted a case-control study in Hong Kong Chinese children over a 4
      year period in the Duchess of Kent Children's Hospital. Consecutive medical
      records of all new referrals below 5 years of age were reviewed and children
      diagnosed with SLI (case) were compared with those referred with other
      developmental and behavioural problems who had been assessed as having normal
      language and overall development (control) using the Griffiths Mental
      Developmental Scale. SLI was defined as those with a language quotient more than
      one standard deviation below the mean and below the general developmental
      quotient in children with normal general developmental quotient, but without
      neurological or other organic diseases. We used binary and ordinal logistic
      regression to assess any association between SLI and multilingual exposure at
      home, adjusting for age and gender of subjects, parental age, education level and
      occupational status, number of siblings, family history of language delay and
      main caregiver at home. Multivariable linear regression was used to examine the
      effect of covariates on the language comprehension and expression standard scores
      assessed by the Reynell Developmental Language Scale. A total of 326 cases and
      304 controls were included. The mean ages of cases and controls were 2.56 and
      2.89 years respectively. Boys predominated in both groups (cases, 75.2%;
      controls, 60.2%). The children were exposed to between one and four languages at
      home, the major ones being Cantonese Chinese followed by English. The adjusted
      odds ratio (OR) of SLI was 2.94; [95% confidence interval (CI) 1.82, 4.74] for
      multilingual compared with monolingual exposure. A significant linear dose
      response relationship was found (OR of SLI = 2.58 [1.72, 3.88] for each
      additional language to which the child was exposed). Male gender (OR = 1.88
      [1.24, 2.87]), positive family history (OR = 2.01 [1.17, 3.47]), lower education
      levels of parents (P = 0.028 for father, P = 0.038 for mother) and lower
      occupational status of father (P = 0.005) were also risk factors for SLI.
      Multilingual exposure also significantly reduced the language quotient (P =
      0.012) and language comprehension standard score (P = 0.016) of children with
      SLI, but not of normal children. We concluded that multilingual home environment
      is associated with SLI with a dose-response relationship. Exposure to multiple
      languages might adversely affect subsequent language ability.

PMID- 15958154
TI  - Probability samples of area births versus clinic populations for reproductive
      epidemiology studies.
AB  - Studies of pregnancy outcome are generally based either on geographically defined
      populations, often from birth records, or on clinic or hospital populations. We
      compared women recruited into a clinic-based study, the Pregnancy, Infection, and
      Nutrition (PIN) Study, with women who resided in the geographical area of the
      study (Alamance, Orange, and Wake Counties in North Carolina) and gave birth over
      the corresponding time period (1996-2000). Clinic participants were more likely
      to be Black, younger, have lower education, be unmarried, have a more frequent
      history of adverse pregnancy outcome, obtain prenatal care later, and smoke more
      cigarettes. Despite that profile, the proportion of clinic participants
      delivering preterm was somewhat lower than among area women overall (10.8% vs.
      11.3%). Black/White risk ratios for preterm birth were markedly different for
      area (1.6) vs. clinic women (1.1), whereas other predictors were similar.
      Patterns may differ across groups for many reasons, including self-selection of
      clinics and varying clinical practices.

PMID- 15958155
TI  - Evaluation of neonatal verbal autopsy using physician review versus algorithm
      based cause-of-death assignment in rural Nepal.
AB  - Verbal autopsy (VA) is used to ascertain cause-specific neonatal mortality using
      parental/familial recall. We sought to compare agreement between causes of death
      obtained from the VA by physician review vs. computer-based algorithms. Data were
      drawn from a cluster-randomised trial involving 4130 live-born infants and 167
      neonatal deaths in the rural Sarlahi District of Nepal. We examined the agreement
      between causes ascertained by physician review and algorithm assignment by the
      kappa (kappa) statistic. We also compared responses to identical questions posed
      posthumously during neonatal VA interviews with those obtained during maternal
      interviews and clinical examinations regarding condition of newborns soon after
      birth. Physician reviewers assigned prematurity or acute lower respiratory
      infection (ALRI) as causes of 48% of neonatal deaths; 41% were assigned as
      uncertain. The algorithm approach assigned sepsis (52%), ALRI (31%), birth
      asphyxia (29%), and prematurity (24%) as the most common causes of neonatal
      death. Physician review and algorithm assignment of causes of death showed high
      kappa for prematurity (0.73), diarrhoea (0.81) and ALRI (0.68), but was low for
      congenital malformation (0.44), birth asphyxia (0.17) and sepsis (0.00).
      Sensitivity and specificity of VA interview questions varied by symptom, with
      positive predictive values ranging from 50% to 100%, when compared with maternal
      interviews and examinations of neonates soon after birth. Analysis of the VA data
      by physician review and computer-based algorithms yielded disparate results for
      some causes but not for others. We recommend an analysis technique that combines
      both methods, and further validation studies to improve performance of the VA for
      assigning causes of neonatal death.

PMID- 15958156
TI  - Seroprevalence and risk factors for toxoplasma infection among pregnant women in
      Aydin province, Turkey.
AB  - BACKGROUND: The aims of the present study were to determine the prevalence of
      toxoplasmosis in pregnant women at first trimester of their pregnancy and to
      follow up the seroconversion for next two trimesters, and to identify the risk
      factors and possible contamination routes in Aydin province, Turkey. METHOD: The
      sample size was calculated as 423 on a prevalence of 50%, d=0.05 at a confidence
      level of 95% with 10% addition. It was a cross-sectional study with multistage
      sampling. After a questionnaire applied to the pregnant women, anti-Toxoplasma
      IgG antibodies were studied with ELISA and IFA, values in conflict with DA test,
      where IgM antibodies were studied with ELISA and for borderline or positive
      values of IgM avidity test was used. RESULTS: The mean age of 389 (92.9%) of
      pregnant women in the study was 24.28+/-4.56 years, the seroprevalence of anti
      Toxoplasma IgG antibodies for toxoplasmosis was 30.1%. Seroprevalence was
      increased with age (p=0.001) and with drinking water consumption other than
      bottled water (p=0.042). No significant relations were observed between anti
      Toxoplasma IgG antibodies and education level, being native or migrant, abortion
      history, consumption of meat, vegetable and milk/milk products, personal or
      kitchen hygiene habits, cat owning at home of the pregnant women. No IgM antibody
      was detected. CONCLUSION: One of every three pregnant women in Aydin was at risk
      of toxoplasmosis at the first trimester of their pregnancy. Increased
      seroprevalance with age was a predictable result because of increasing time of
      exposure. Increased seroprevalence with consumption of municipal and uncontrolled
      water (well/spring water) supplies was similar with latest epidemiological
      findings.

PMID- 15958157
TI  - Dynamic in vitro measurement of patellar movement after total knee arthroplasty:
      an in vitro study.
AB  - BACKGROUND: Changing the kinematic behaviour of patellar movement could be one of
      the reasons for anterior knee pain after implantation of a total knee
      arthroplasty (TKA). The aim of the current study was to measure the potential
      influence on patellar kinematics of patellar resurfacing during TKA. METHODS:
      Patellar movement before and after TKA with and without patellar resurfacing was
      measured under dynamic conditions in an in vitro cadaver simulation. Physiologic
      Musculus quadriceps forces were applied to five physiologic human knee specimens
      undergoing simulated isokinetic extension motions, patellar movement was measured
      using an ultrasonic measurement system. Thereafter, the Interax I.S.A.-prosthesis
      system was implanted without and with resurfacing the patella, and patellar
      movement was again measured. RESULTS: The physiologic patella center moved on a
      semilunar path up to 6.4 mm (SD 6.4 mm) medially during extension. After TKA, the
      unresurfaced patella showed significantly less medial translation (p = 0.04) than
      the resurfaced patella. Subsequent resurfacing of the patella then resulted in a
      return to mediolateral positioning of the patella similar to the physiological
      case, whereas the resurfaced patella tilted up to twice as much as physiologic.
      CONCLUSION: The results of this study suggest that resurfacing of the patella
      during TKA can result in a restoration of the physiologic mediolateral shift of
      the patellofemoral joint while angulation of the patella remains unphysiologic.

PMID- 15958158
TI  - Long term remission of metastatic placental site trophoblastic tumor (PSTT): Case
      report and review of literature.
AB  - BACKGROUND: Placental site trophoblastic tumor (PSTT) is a rare and unique form
      of gestational trophoblastic disease (GTD). This tumor represents a neoplastic
      transformation of intermediate trophoblastic cells. We document a case of long
      term remission in a patient with metastatic PSTT. CASE PRESENTAION: A 27-year-old
      patient with metastatic PSTT was treated with combination therapy (chemotherapy
      and surgery). Patient is alive after 10 years without any evidence of recurrence.
      Literature on PSTT was searched using Medline and cross references, and pertinent
      articles were reviewed. CONCLUSION: With surgery and chemotherapy it is possible
      to achieve long-term remission in metastatic PSTT. Only a handful of previously
      reported cases with prolonged remission had been treated with the described
      combined chemotherapy and surgical approach. We suggest that this approach may be
      recommended for metastatic PSTT.

PMID- 15958159
TI  - Transdermal fentanyl for the treatment of pain caused by osteoarthritis of the
      knee or hip: an open, multicentre study.
AB  - BACKGROUND: This study was designed to evaluate the utility of transdermal
      fentanyl (TDF, Durogesic) for the treatment of pain due to osteoarthritis (OA) of
      the knee or hip, which was not adequately controlled by non-opioid analgesics or
      weak opioids. The second part of the trial, investigating TDF in patients with
      rheumatoid arthritis (RA) is reported separately. METHODS: Current analgesia was
      optimised during a 1-week run-in. Patients then received 28 days treatment with
      TDF starting at 25 microg/hr, with the option to increase the dose until adequate
      pain control was achieved. Metoclopramide was taken during the first week and
      then as needed. RESULTS: Of the 159 patients recruited, 75 with OA knee and 44
      with OA hip completed the treatment phase, 30 knee and 18 hip patients entered
      the one-week taper-off phase. The most frequently used maximum dose of TDF was 25
      microg/hr. The number of patients with adequate pain control increased during the
      run-in period from 4% to 27%, and further increased during TDF treatment to 88%
      on day 28. From baseline to endpoint, there were significant reductions in pain
      (p < 0.001) and improvements in functioning (p < 0.001) and physical (p < 0.001)
      and mental (p < 0.05) health. Scores for 'pain right now' decreased significantly
      within 24 hours of starting TDF treatment. TDF was assessed favourably and 84% of
      patients would recommend it for OA-related pain. Nausea and vomiting were the
      most common adverse events (reported by 32% and 26% of patients respectively),
      despite prophylaxis with metoclopramide, which showed limited efficacy in this
      setting. CONCLUSION: TDF significantly increased pain control, and improved
      functioning and quality of life. Metoclopramide appeared to be of limited value
      in preventing nausea and vomiting; more effective anti-emetic treatment may
      enable more people to benefit from strong opioids such as TDF. This study
      suggests that four weeks is a reasonable period to test the benefit of adding TDF
      to improve pain control in OA patients and that discontinuing therapy in cases of
      limited benefit creates no major obstacles.

PMID- 15958160
TI  - The effect of functional splinting on mild dysplastic hips after walking onset.
AB  - BACKGROUND: For treatment of Graf class IIb dysplastic hips at walking onset a
      treatment concept with abduction splints allowing patterns as walking and
      crawling under constant abduction control was investigated. However, as the
      splint still incapacitates child movements the research question remains whether
      the physiologically progressing maturation of hips can be significantly altered
      using such abduction splints for walking children. METHODS: Of 106 children
      showing late hip dysplasia, 68 children treated with the Hoffman-Daimler (HD
      splint) abduction splint were compared with 38 children with neglect of the
      abduction treatment in this retrospective study. Radiographic analyses were
      performed measuring the development of the age dependent acetabular angle.
      RESULTS: The regression analysis for splint treatment showed a significant linear
      regression for both splint treatment and no splint treatment group (r2 = 0.31
      respectively r2 = 0.33). No statistical difference between both treatment groups
      was apparent. CONCLUSION: Considering the characteristics of this study, there
      seems to be no strong rationale supporting the use of an abduction device in
      growing children. As no significant difference between treatment groups is
      apparent, a future controlled prospective study on splinting effects can be
      considered ethically allowed.

PMID- 15958161
TI  - Alkahest NuclearBLAST : a user-friendly BLAST management and analysis system.
AB  - BACKGROUND: Sequencing of EST and BAC end datasets is no longer limited to large
      research groups. Drops in per-base pricing have made high throughput sequencing
      accessible to individual investigators. However, there are few options available
      which provide a free and user-friendly solution to the BLAST result storage and
      data mining needs of biologists. RESULTS: Here we describe NuclearBLAST, a batch
      BLAST analysis, storage and management system designed for the biologist. It is a
      wrapper for NCBI BLAST which provides a user-friendly web interface which
      includes a request wizard and the ability to view and mine the results. All BLAST
      results are stored in a MySQL database which allows for more advanced data-mining
      through supplied command-line utilities or direct database access. NuclearBLAST
      can be installed on a single machine or clustered amongst a number of machines to
      improve analysis throughput. NuclearBLAST provides a platform which eases data
      mining of multiple BLAST results. With the supplied scripts, the program can
      export data into a spreadsheet-friendly format, automatically assign Gene
      Ontology terms to sequences and provide bi-directional best hits between two
      datasets. Users with SQL experience can use the database to ask even more complex
      questions and extract any subset of data they require. CONCLUSION: This tool
      provides a user-friendly interface for requesting, viewing and mining of BLAST
      results which makes the management and data-mining of large sets of BLAST
      analyses tractable to biologists.

PMID- 15958162
TI  - Evidence that the delay-period activity of dopamine neurons corresponds to reward
      uncertainty rather than backpropagating TD errors.

PMID- 15958163
TI  - Infrared thermography fails to visualize stimulation-induced meridian-like
      structures.
AB  - BACKGROUND: According to Traditional Chinese Medicine (TCM) the vital energy
      flows through a system of channels also called meridians. Generally accepted
      proof for meridians cannot be considered as being given. Goal of this study was
      to examine whether possible stimulation-induced meridian-like structures, as
      recently described by other authors, can be visualized and objectified
      simultaneously at different infrared wavelength ranges. METHODS: The study
      analyses evidence for the existence of acupuncture-specific, meridian-like
      artifacts in 6 healthy volunteers (mean age +/- SD 28.7 +/- 3.7 years; range 25 -
      35 years). Two infrared cameras at different wavelength ranges were used for
      thermographic control of possible stimulation effects (moxibustion-cigar,
      infrared warmth stimulation, needle and laserneedle stimulation). In addition to
      thermography, temperature and microcirculatory parameters were registered at a
      selected point using laser-Doppler flowmetry. RESULTS AND CONCLUSION: After
      moxibustion (or infrared light stimulation) of the body at 2 - 5 microm and 7.5 -
      13 microm ranges, different structures appear on thermographic images of the
      human body which are technical artifacts and which are not identical to what are
      known as meridians in all textbooks of TCM. Further scientific studies are
      required regarding the possible visualization of meridians.

PMID- 15958165
TI  - Feature selection and classification for microarray data analysis: evolutionary
      methods for identifying predictive genes.
AB  - BACKGROUND: In the clinical context, samples assayed by microarray are often
      classified by cell line or tumour type and it is of interest to discover a set of
      genes that can be used as class predictors. The leukemia dataset of Golub et al.
      1 and the NCI60 dataset of Ross et al. 2 present multiclass classification
      problems where three tumour types and nine cell lines respectively must be
      identified. We apply an evolutionary algorithm to identify the near-optimal set
      of predictive genes that classify the data. We also examine the initial gene
      selection step whereby the most informative genes are selected from the genes
      assayed. RESULTS: In the absence of feature selection, classification accuracy on
      the training data is typically good, but not replicated on the testing data. Gene
      selection using the RankGene software 3 is shown to significantly improve
      performance on the testing data. Further, we show that the choice of feature
      selection criteria can have a significant effect on accuracy. The evolutionary
      algorithm is shown to perform stably across the space of possible parameter
      settings - indicating the robustness of the approach. We assess performance using
      a low variance estimation technique, and present an analysis of the genes most
      often selected as predictors. CONCLUSION: The computational methods we have
      developed perform robustly and accurately, and yield results in accord with
      clinical knowledge: A Z-score analysis of the genes most frequently selected
      identifies genes known to discriminate AML and Pre-T ALL leukemia. This study
      also confirms that significantly different sets of genes are found to be most
      discriminatory as the sample classes are refined.

PMID- 15958164
TI  - PI3K and PKC contribute to membrane depolarization mediated by alpha2
      adrenoceptors in the canine isolated mesenteric vein.
AB  - BACKGROUND: Norepinephrine (NE), a classic neurotransmitter in the sympathetic
      nervous system, induces vasoconstriction of canine isolated mesenteric vein that
      is accompanied by a sustained membrane depolarization. The mechanisms underlying
      the NE-elicited membrane depolarization remain undefined. In the present study we
      hypothesized that phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC)
      are involved in the electrical field stimulation (EFS)-induced slow membrane
      depolarization (SMD) in canine isolated mesenteric vein. EFS (0.1-2 Hz, 0.1 ms,
      15V, 10 s)-induced changes in the membrane potential were recorded with a
      conventional intracellular microelectrode technique and evaluated in the absence
      and presence of inhibitors of neuronal activity, alpha-adrenoceptors, membrane
      ion channels, PI3K, inositol 1,4,5-triphosphate (InsP3) receptors, and PKC.
      Activation of PI3Kgamma and PKCzeta in response to exogenous NE and clonidine in
      the absence and presence of receptor and kinase inhibitors were also determined.
      RESULTS: Contractile responses to NE and clonidine (0.05 - 10 microM) were
      significantly diminished in the presence of yohimbine (0.1 microM). Exogenous NE
      (0.1 microM) and clonidine (1 microM) elicited SMD. The resting membrane
      potential of canine mesenteric vein smooth muscle cells was -68.8 +/- 0.8 mV. EFS
      elicited a biphasic depolarization comprised of excitatory junction potentials
      and SMD that are purinergic and adrenergic in nature, respectively. The magnitude
      of the SMD in response to EFS at 0.5 Hz was 9.4 +/- 0.7 mV. This response was
      reduced by 65-98% by the fast Na+ channel inhibitor tetrodotoxin (1 microM), by
      the inhibitor of N-type Ca2+ channels omega-conotoxin GVIA (5 nM), the non
      selective alpha-adrenoceptor blocker phentolamine (1 microM), the selective
      alpha2-adrenoceptor blocker yohimbine (0.1 microM), the ion channel inhibitors
      niflumic acid (NFA, 100 microM), 5-nitro-2-(3-phenylpropylamino) benzoic acid
      (NPPB, 30 microM), 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS, 200
      microM), and Gd3+ (30 microM), and the PI3K inhibitors wortmannin (100 nM) and LY
      294002 (10 microM). The SMD remained unchanged in the presence of the L-type Ca2+
      channel blocker nicardipine (1 microM) and the InsP3 receptor blockers 2
      aminoethoxydiphenylborate (2APB, 50 microM) and xestospongin C (3 microM). The
      inhibitor of PKC chelerythrine (1 microM), but not calphostin C (10 microM),
      diminished the SMD. Exogenous NE and clonidine (1 microM each) activated both
      PI3Kgamma and PKCzeta, and the activation of these kinases was abolished by
      preincubation of tissue with the alpha2-adrenoceptor blocker yohimbine.
      CONCLUSION: Neuronally-released NE stimulates smooth muscle alpha2-adrenoceptors
      and activates PI3K and atypical PKC in the canine mesenteric vein. Events
      downstream of PKC lead to SMD and vasoconstriction. This represents a novel
      pathway for NE-induced membrane depolarization in a vascular smooth muscle
      preparation.

PMID- 15958166
TI  - Comparative 3-D modeling of tmRNA.
AB  - BACKGROUND: Trans-translation releases stalled ribosomes from truncated mRNAs and
      tags defective proteins for proteolytic degradation using transfer-messenger RNA
      (tmRNA). This small stable RNA represents a hybrid of tRNA- and mRNA-like domains
      connected by a variable number of pseudoknots. Comparative sequence analysis of
      tmRNAs found in bacteria, plastids, and mitochondria provides considerable
      insights into their secondary structures. Progress toward understanding the
      molecular mechanism of template switching, which constitutes an essential step in
      trans-translation, is hampered by our limited knowledge about the three
      dimensional folding of tmRNA. RESULTS: To facilitate experimental testing of the
      molecular intricacies of trans-translation, which often require appropriately
      modified tmRNA derivatives, we developed a procedure for building three
      dimensional models of tmRNA. Using comparative sequence analysis,
      phylogenetically-supported 2-D structures were obtained to serve as input for the
      program ERNA-3D. Motifs containing loops and turns were extracted from the known
      structures of other RNAs and used to improve the tmRNA models. Biologically
      feasible 3-D models for the entire tmRNA molecule could be obtained. The models
      were characterized by a functionally significant close proximity between the tRNA
      like domain and the resume codon. Potential conformational changes which might
      lead to a more open structure of tmRNA upon binding to the ribosome are
      discussed. The method, described in detail for the tmRNAs of Escherichia coli,
      Bacillus anthracis, and Caulobacter crescentus, is applicable to every tmRNA.
      CONCLUSION: Improved molecular models of biological significance were obtained.
      These models will guide in the design of experiments and provide a better
      understanding of trans-translation. The comparative procedure described here for
      tmRNA is easily adopted for the modeling the members of other RNA families.

PMID- 15958167
TI  - Acquisition of rifabutin resistance by a rifampicin resistant mutant of
      Mycobacterium tuberculosis involves an unusual spectrum of mutations and elevated
      frequency.
AB  - BACKGROUND: Mutations in a small region of the rpoB gene are responsible for most
      rifamycin resistance in Mycobacterium tuberculosis. In this study we have
      sequentially generated resistant strains to first rifampicin and then rifabutin.
      Portions of the rpoB gene were sequenced from 131 randomly selected mutants.
      Second round selection resulted in a changed frequency of specific mutations.
      METHODS: Mycobacterium tuberculosis (strain Mtb72) rifamycin resistant mutants
      were selected in vitro with either rifampicin or rifabutin. One mutant R190 (rpoB
      S522L) selected with rifampicin had a rifampicin MIC of 32 microg/ml but remained
      sensitive to rifabutin (MIC<0.8 microg/ml). This mutant was subjected to a second
      round of selection with rifabutin. RESULTS: All 105 first round resistant mutants
      derived from the parent strain (Mtb72) screened acquired mutations within the 81
      bp rpoB hotspot. When the rifampicin resistant but rifabutin sensitive S522L
      mutant was subjected to a second round of selection, single additional rpoB
      mutations were identified in 24 (92%) of 26 second round mutants studied, but 14
      (54%) of these strains contained mutations outside the 81 bp hotspot (codons 144,
      146, 148, 505). Additionally, spontaneous rifabutin resistant mutants were
      produced at >10 times the frequency by the S522L mutant than the parent strain.
      CONCLUSION: First round selection of mutation S522L with rifampicin increased the
      frequency and changed the spectrum of mutations identified after selection with
      rifabutin.

PMID- 15958168
TI  - Test-retest reliability of a questionnaire to assess physical environmental
      factors pertaining to physical activity.
AB  - BACKGROUND: Despite the documented benefits of physical activity, many adults do
      not obtain the recommended amounts. Barriers to physical activity occur at
      multiple levels, including at the individual, interpersonal, and environmental
      levels. Only until more recently has there been a concerted focus on how the
      physical environment might affect physical activity behavior. With this new area
      of study, self-report measures should be psychometrically tested before use in
      research studies. Therefore the objective of this study was to document the test
      retest reliability of a questionnaire designed to assess physical environmental
      factors that might be associated with physical activity in a diverse adult
      population. METHODS: Test and retest surveys were conducted over the telephone
      with 106 African American and White women and men living in either Forsyth
      County, North Carolina or Jackson, Mississippi. Reliability of self-reported
      environmental factors across four domains (e.g., access to facilities and
      destinations, functionality and safety, aesthetics, natural environment) was
      determined using intraclass correlation coefficients (ICC) overall and separately
      by gender and race. RESULTS: Generally items displayed moderate and sometimes
      substantial reliability (ICC between 0.4 to 0.8), with a few differences by
      gender or race, across each of the domains. CONCLUSION: This study provides some
      psychometric evidence for the use of many of these questions in studies examining
      the effect of self-reported physical environmental measures on physical activity
      behaviors, among African American and White women and men.

PMID- 15958169
TI  - A comparison of ultrasound measurements to assess carotid atherosclerosis
      development in subjects with and without type 2 diabetes.
AB  - BACKGROUND: Subjects with type 2 diabetes are at an increased risk of vascular
      complications. The use of carotid ultrasound remains an attractive, non-invasive
      method to monitor atherosclerotic disease progression and/or response to
      treatment in patients with type 2 diabetes, with intima-media thickness routinely
      used as the gold standard to detect pathology. However, alternative measurements,
      such as plaque area or volume, may represent a potentially more powerful
      approach. Thus, the objective of this study was to compare the traditional intima
      media thickness measurement against the novel total plaque volume measurement in
      analyzing carotid atherosclerosis development in individuals with type 2
      diabetes. METHODS: The case-control study included 49 Oji-Cree adults with
      diabetes or impaired glucose tolerance, aged 21-69, and 49 sex- and age-matched
      normoglycemic subjects. At baseline, metabolic variables were measured, including
      body mass index, waist circumference, total cholesterol: high density lipoprotein
      ratio, plasma triglycerides, plasma glucose, and serum insulin. Carotid
      ultrasound measurements, 7 years later, assessed carotid arterial intima-media
      thickness and total plaque volume. RESULTS: At baseline, the two groups were well
      matched for smoking habits, hypertension, body mass index, and waist
      circumference. Differences were noted in baseline measurements of total
      cholesterol:high density lipoprotein (P = 0.0006), plasma triglycerides (P <
      0.0001) and fasting glucose (P < 0.0001). After seven years, carotid ultrasound
      scans revealed that total plaque volume measurements (P = 0.037), but not intima
      media thickness measurements, were higher in subjects with diabetes/impaired
      glucose tolerance compared to the normoglycemic controls. Correlation between
      intima-media thickness and total plaque volume was moderate. Based on our study
      findings, to achieve power levels > 0.70 when comparing intima-media thickness
      measurements for diabetics versus non-diabetics, thousands of study subjects are
      required. For comparing total plaque volume measurements, only hundreds of study
      subjects are required. CONCLUSION: The development of atherosclerotic plaque is
      greater in subjects with diabetes/impaired glucose tolerance. Total plaque volume
      appears to capture the atherosclerotic disease burden more effectively in
      subjects with type 2 diabetes, and would be an appropriate outcome measure for
      studies aimed at changing the diabetic milieu.

PMID- 15958170
TI  - A prospective study of cumulative job stress in relation to mental health.
AB  - BACKGROUND: This study tests associations between psychosocial stress at work
      measured by the effort-reward imbalance model in a dynamic perspective, and
      multiple indicators of poor mental health, in a prospective design. METHODS: 1986
      male and female employees from four Belgian enterprises were followed-up over one
      year within the framework of the Somstress study. Based on two consecutive
      measurements, an index of cumulative job stress was constructed and its
      associations with five indicators of mental health were studied, excluding
      caseness at entry (for depression, anxiety, somatisation, chronic fatigue and
      psychotropic drug consumption respectively). Taking into account the longitudinal
      design, four categories of job stress are defined: 1) employees free from stress
      at both measures, 2) job stress present at first measure but not at the second
      one, 3) recent onset of job stress as evidenced by second measure 4) workers
      exposed to stress at both measures. Multivariate logistic regression with
      appropriate adjustments was applied. RESULTS: In bivariate analysis, a clear
      graded association of cumulative job stress with all five mental health
      indicators is observed, both in men and women. In multivariate logistic
      regression analysis, recent onset of stress is strongly associated with poor
      mental health among men (odds ratios ranging from 1.8 to 4.6), while cumulative
      stress shows strongest effects on mental health in women (odds ratios ranging
      from 1.4 to 7.1). CONCLUSION: Cumulative experience and recent onset of job
      stress in terms of high effort spent and low reward received is associated with
      elevated risk of all five indicators of poor mental health at follow-up in a
      large cohort of employees.

PMID- 15958171
TI  - Contribution of anaerobic energy expenditure to whole body thermogenesis.
AB  - Heat production serves as the standard measurement for the determination of
      energy expenditure and efficiency in animals. Estimations of metabolic heat
      production have traditionally focused on gas exchange (oxygen uptake and carbon
      dioxide production) although direct heat measurements may include an anaerobic
      component particularly when carbohydrate is oxidized. Stoichiometric
      interpretations of the ratio of carbon dioxide production to oxygen uptake
      suggest that both anaerobic and aerobic heat production and, by inference, all
      energy expenditure--can be accounted for with a measurement of oxygen uptake as
      21.1 kJ per liter of oxygen. This manuscript incorporates contemporary
      bioenergetic interpretations of anaerobic and aerobic ATP turnover to promote the
      independence of these disparate types of metabolic energy transfer: each has
      different reactants and products, uses dissimilar enzymes, involves different
      types of biochemical reactions, takes place in separate cellular compartments,
      exploits different types of gradients and ultimately each operates with distinct
      efficiency. The 21.1 kJ per liter of oxygen for carbohydrate oxidation includes a
      small anaerobic heat component as part of anaerobic energy transfer. Faster rates
      of ATP turnover that exceed mitochondrial respiration and that are supported by
      rapid glycolytic phosphorylation with lactate production result in heat
      production that is independent of oxygen uptake. Simultaneous direct and indirect
      calorimetry has revealed that this anaerobic heat does not disappear when lactate
      is later oxidized and so oxygen uptake does not adequately measure anaerobic
      efficiency or energy expenditure (as was suggested by the "oxygen debt"
      hypothesis). An estimate of anaerobic energy transfer supplements the measurement
      of oxygen uptake and may improve the interpretation of whole-body energy
      expenditure.

PMID- 15958172
TI  - Thesaurus-based disambiguation of gene symbols.
AB  - BACKGROUND: Massive text mining of the biological literature holds great promise
      of relating disparate information and discovering new knowledge. However,
      disambiguation of gene symbols is a major bottleneck. RESULTS: We developed a
      simple thesaurus-based disambiguation algorithm that can operate with very little
      training data. The thesaurus comprises the information from five human genetic
      databases and MeSH. The extent of the homonym problem for human gene symbols is
      shown to be substantial (33% of the genes in our combined thesaurus had one or
      more ambiguous symbols), not only because one symbol can refer to multiple genes,
      but also because a gene symbol can have many non-gene meanings. A test set of
      52,529 Medline abstracts, containing 690 ambiguous human gene symbols taken from
      OMIM, was automatically generated. Overall accuracy of the disambiguation
      algorithm was up to 92.7% on the test set. CONCLUSION: The ambiguity of human
      gene symbols is substantial, not only because one symbol may denote multiple
      genes but particularly because many symbols have other, non-gene meanings. The
      proposed disambiguation approach resolves most ambiguities in our test set with
      high accuracy, including the important gene/not a gene decisions. The algorithm
      is fast and scalable, enabling gene-symbol disambiguation in massive text mining
      applications.

PMID- 15958173
TI  - Quantification of resting myocardial blood flow velocity in normal humans using
      real-time contrast echocardiography. A feasibility study.
AB  - BACKGROUND: Real-time myocardial contrast echocardiography (MCE) is a novel
      method for assessing myocardial perfusion. The aim of this study was to evaluate
      the feasibility of a very low-power real-time MCE for quantification of regional
      resting myocardial blood flow (MBF) velocity in normal human myocardium. METHODS:
      Twenty study subjects with normal left ventricular (LV) wall motion and normal
      coronary arteries, underwent low-power real-time MCE based on color-coded pulse
      inversion Doppler. Standard apical LV views were acquired during constant IV.
      infusion of SonoVue. Following transient microbubble destruction, the contrast
      replenishment rate (beta), reflecting MBF velocity, was derived by plotting
      signal intensity vs. time and fitting data to the exponential function; y (t) =A
      (1-e(-beta(t-t0))) + C. RESULTS: Quantification was feasible in 82%, 49% and 63%
      of four-chamber, two-chamber and apical long-axis view segments, respectively.
      The LAD (left anterior descending artery) and RCA (right coronary artery)
      territories could potentially be evaluated in most, but contrast detection in the
      LCx (left circumflex artery) bed was poor. Depending on localisation and which
      frames to be analysed, mean values of beta were 0.21-0.69 s(-1), with higher
      values in medial than lateral, and in basal compared to apical regions of scan
      plane (p = 0.03 and p < 0.01). Higher beta-values were obtained from end-diastole
      than end-systole (p < 0.001), values from all-frames analysis lying between.
      CONCLUSION: Low-power real-time MCE did have the potential to give contrast
      enhancement for quantification of resting regional MBF velocity. However, the
      technique is difficult and subjected to several limitations. Significant
      variability in beta suggests that this parameter is best suited for with-in
      patient changes, comparing values of stress studies to baseline.

PMID- 15958174
TI  - Tools for the detection and quantitation of protein transglutamination.

PMID- 15958175
TI  - Whole-cell-reporter-gene-based biosensing systems on a compact disk microfluidics
      platform.
AB  - Biosensing systems such as reporter-gene-based whole-cell assays are increasingly
      finding applications in biological and environmental screening. A whole-cell
      approach to such analyses can provide valuable information about the bioavailable
      level of a compound of interest. These biosensing systems rely on the molecular
      recognition of a specific analyte by a regulatory protein and, therefore, can
      detect low levels of the target analyte. In this study, Escherichia coli cells
      containing plasmid pSD10 were engineered to sense the model target analytes
      arsenite and antimonite, the target analytes in this study. The biosensing system
      takes advantage of the recognition of the regulatory protein, ArsR, for arsenite
      and antimonite to produce the reporter protein, which in this case is GFPuv. The
      fluorescence emitted by the GFPuv in the cells can be directly related to the
      concentration of the analyte in the cell, making this biosensing system useful in
      the detection of arsenite and/or antimonite in a variety of samples.
      Miniaturization of biosensing systems can further enhance their utility by
      decreasing reagent consumption and analysis time and by allowing for the high
      throughput screening of samples. To that end, we employed a microcentrifugal
      microfluidics platform that has low power, space, and reagent requirements,
      increased speed of detection, and the potential for portability. Herein, we
      demonstrate for the first time the adaptation of a whole-cell sensing system to a
      microcentrifugal microfluidics platform. Moreover, we were able to detect our
      target analytes in a rapid and sensitive manner compared to conventional sensing
      methods.

PMID- 15958176
TI  - Fluorogenic peptide substrates containing benzoxazol-5-yl-alanine derivatives for
      kinetic assay of cysteine proteases.
AB  - New peptide substrates containing benzoxazol-5-yl-alanine derivatives for kinetic
      assay of cysteine proteases have been synthesized and characterized. The
      substrates are peptides internally quenched by the intramolecular fluorescence
      resonance energy transfer. The results demonstrate that the kind of donor
      acceptor pair (D-A) significantly affects the kinetic parameters of the enzymatic
      process. The three longest peptides, Box-Lys-Phe-Gly-Gly-Ala-Ala-Tyr(NO2)
      containing Box-alanine derivative as a donor and nitro-tyrosine as an acceptor,
      show two times greater affinity to papain than does the one peptide possessing
      Dabcyl-Edans as a D-A pair. Kinetic parameters for the best papain substrate, Lys
      Box(benzfur)-Gly-Gly-Ala-Ala-Tyr(NO2), are Km = 6.85+/-0.59 microM, kcat = 19.51
      s(-1), and kcat/Km = 2.85 microM(-1) s(-1). It was found that the peptides
      Box(benzfur)-Lys-Phe-Gly-Gly-Tyr(NO2) and Box(benzfur)-Phe-Gly-Gly-Tyr(NO2) were
      also hydrolyzed by cathepsin B with the highest speed of hydrolysis as a result
      of carboxypeptidase activity of this enzyme. Moreover, these substrates show high
      affinity and selectivity to this enzyme.

PMID- 15958177
TI  - Scaling up a microbore separation for semipreparative analysis: differential
      recoveries of radiolabeled amino acids.
AB  - Application of a high-sensitivity microbore system designed to separate and
      quantify nonderivatized amino acids by anion exchange chromatography and
      amperometric detection for determination of amino acid-specific activities in
      biological samples requires high capacity to recover sufficient labeled material
      for adequate count statistics. Scale up from a low (25-1000 pmol) to a high (500
      15,000 pmol) working range was achieved by use of a thick working electrode
      gasket to reduce sensitivity and eliminate peak splitting and tailing and by
      modification of the wash procedure to eliminate carryover. Analysis of recoveries
      of labeled amino acids revealed that specific amino acids are either selectively
      retained on the column or partially degraded during analysis and that assessment
      of purities of labeled compounds and metabolic labeling patterns requires careful
      analysis of recoveries of labeled compounds in the appropriate eluate fraction.

PMID- 15958178
TI  - A potency assay for a replication incompetent adenovirus type 5 carrying a human
      fgf-4 gene.
AB  - A bioassay that measures the potency of the FGF-4 transgene carried by a
      replication incompetent adenovirus type 5, Ad5FGF-4, was developed on ARPE-19
      cells. The assay is carried out in a microtiter plate format and measures
      cellular proliferation following infection of ARPE-19 cells with a serial
      dilution of Ad5FGF-4. Proliferation is measured as a percentage increase in
      absorbance reading in relation to a mock-infected control. Ad5LacZ and Ad5FGF-4
      viruses treated similarly to the test sample are included as negative and
      positive controls, respectively. The increased absorbance reading resulting from
      infection with the virus correlates with FGF-4 production as determined by an FGF
      4 enzyme-linked immunosorbent assay, an increase in de novo DNA synthesis as
      measured by BrdU incorporation, and an increase in the total cell number. The
      assay shows a dose-dependent response and is capable of evaluating the stability
      of Ad5FGF-4. A sample being tested is compared with a reference standard, and the
      relative potency value is obtained by a parallel line analysis of the dose
      response curve of the test article in relation to the reference standard.
      Therefore, this procedure can be used as an in vitro efficacy-indicating assay,
      demonstrating that the FGF-4 transgene product carried by Ad5FGF-4 is
      biologically active.

PMID- 15958179
TI  - Application of high-performance liquid chromatography-electrospray ionization
      mass spectrometry to measure microsomal membrane transport of glucuronides.
AB  - A primary reason for poor characterization of microsomal transport to date is the
      limitations of the measurement techniques used. Radiodetection provides
      sufficient sensitivity, but it can be applied only when labeled analogue is
      available. In this article, we report the novel application of high-performance
      liquid chromatography and electrospray tandem mass spectrometry (LC-MS/MS) in
      "rapid filtration" transport assays. The method was developed using glucuronides,
      but it is adaptable to any compound that can be measured with LC-MS/MS. Because
      of the high sensitivity and accuracy of this detection technique, the substrates
      can be used at their physiological concentration in the experiments. The new
      methodology does not require radiolabeling, so it remarkably widens the range of
      possible substrates to investigate and allows simultaneous detection as well as
      monitoring of substrate stability during the experiments.

PMID- 15958180
TI  - Establishment of HEK293 cell line expressing green fluorescent protein-aquaporin
      1 to determine osmotic water permeability.
AB  - Aquaporin (AQP) is a kind of channel-forming membrane glycoprotein that mediates
      osmotic water transport. The present study aimed to establish a cell line stably
      transfected with AQP1 to measure osmotic water permeability. The recombinant
      plasmid was constructed by subcloning the full-length rat AQP1 cDNA into pEGFP-C3
      vector, named pEGFP/AQP1. Human embryonic kidney 293 cells were transfected with
      pEGFP/AQP1 and selected by G418 to obtain a cell line stably expressing AQP1
      tagged with green fluorescent protein. The expression level of AQP1 in the stably
      transfected cell was detected by reverse transcription polymerase chain reaction
      and Western blot. The real-time change of fluorescence density, corresponding to
      cell swelling induced by hyposmotic solution, was recorded under confocal laser
      scanning microscope and used to assess osmotic water permeability. The typical
      AQP1 inhibitor, mercuric chloride, validated this osmotic water permeability
      assay. These results suggested that this transfected cell model could be
      conveniently used to determine osmotic water permeability.

PMID- 15958181
TI  - Cooperativity of paired oligonucleotide probes for microarray hybridization
      assays.
AB  - Synthetic DNA probes attached to microarrays usually range in length from 25 to
      70 nucleotides. There is a compromise between short probes with lower
      sensitivity, which can be accurately synthesized in higher yields, and long
      probes with greater sensitivity but lower synthesis yields. Described here are
      microarrays printed with spots containing a mixture of two short probes, each
      designed to hybridize at noncontiguous sites in the same targeted sequence. We
      have shown that, for a printed microarray, mixed probe spots containing a pair of
      30mers show significantly greater hybridization than spots containing a single
      30mer and can approach the amount of hybridization to spots containing a 60mer or
      a 70mer. These spots with mixed oligonucleotide probes display cooperative
      hybridization signals greater than those that can be achieved by either probe
      alone. Both the higher synthesis yields of short probes and the greater
      sensitivity of long oligonucleotides can be utilized. This strategy provides new
      design options for microarray hybridization assays to detect RNA abundance, RNA
      splice variants, or sequence polymorphisms.

PMID- 15958182
TI  - Determining suitable internal standards for mRNA quantification of increasing
      cancer progression in human breast cells by real-time reverse transcriptase
      polymerase chain reaction.
AB  - Real-time reverse transcriptase polymerase chain reaction is recognized as a
      highly sensitive and specific method for quantification of mRNA expression. SYBR
      green I dye simplifies the experimental design but introduces the need for
      specific controls to maintain high specificity. Due to this increased
      sensitivity, standards that may have been acceptable for normalization of less
      sensitive methods have been shown to vary considerably among cell lines, tissues,
      proliferative states, treatments, and developmental conditions and by degree of
      cancer progression. It has become evident that determination of suitable
      normalization standards is a requirement for the use of this method as it is
      applied toward any new experimental model. We have assessed the suitability of a
      number of commonly used standards for the normalization of mRNAs among a set of
      human breast cancer cell lines of increasing metastatic potential and have
      determined that 18S rRNA and beta-actin (ACTB) mRNA are both suitable for this
      purpose, with each having some limitations. 18S rRNA varies less among the cell
      lines but has a higher degree of random variability, while ACTB mRNA varies more
      among cell lines but has a lower degree of random variation.

PMID- 15958183
TI  - Conformational impurity of disulfide proteins: detection, quantification, and
      properties.
AB  - The conformations of native proteins are in principle, and in most cases,
      dictated by the law of thermodynamics. Accordingly, a native protein must always
      exist in equilibrium with a minor concentration of nonnative (denatured)
      conformational isomers even at nondenaturing conditions. The presence of an
      infinitesimal quantity of nonnative conformational isomers at physiological
      conditions is biologically relevant due to their propensity to aggregate, which
      is an underlying cause of many neurodegenerative diseases. However, their
      detection and quantification are inherently difficult. In this article, we
      describe a simple strategy using the technique of disulfide scrambling to
      identify and quantify such minute concentrations of nonnative isomers. It is
      demonstrated that even for small stable proteins such as epidermal growth factor
      and hirudin, approximately 1% of heterogeneous nonnative isomers coexist with the
      native proteins under physiological conditions.

PMID- 15958184
TI  - A coupled fluorescent assay for histone methyltransferases.
AB  - Histone methyltransferases (HMTs) catalyze the S-adenosylmethionine (AdoMet)
      dependent methylation of lysines and arginines in the nucleosomal core histones
      H3 and H4 and the linker histone H1b. Methylation of these residues regulates
      either transcriptional activation or silencing, depending on the residue modified
      and its degree of methylation. Despite an intense interest in elucidating the
      functions of HMTs in transcriptional regulation, these enzymes have remained
      challenging to quantitatively assay. To characterize the substrate specificity of
      HMTs, we have developed a coupled-fluorescence-based assay for AdoMet-dependent
      methyltransferases. This assay utilizes S-adenosylhomocysteine hydrolase (SAHH)
      to hydrolyze the methyltransfer product S-adenosylhomocysteine (AdoHcy) to
      homocysteine (Hcy) and adenosine (Ado). The Hcy concentration is then determined
      through conjugation of its free sulfhydryl moiety to a thiol-sensitive
      fluorophore. Using this assay, we have determined the kinetic parameters for the
      methylation of a synthetic histone H3 peptide (corresponding to residues 1-15 of
      the native protein) by Schizosaccharomyces pombe CLR4, an H3 Lys-9-specific
      methyltransferase. The fluorescent SAHH-coupled assay allows rapid and facile
      determination of HMT kinetics and can be adapted to measure the enzymatic
      activity of a wide variety of AdoMet-dependent methyltransferases.

PMID- 15958185
TI  - Evaluation of thin films of agarose on glass for hybridization of DNA to identify
      plant pathogens with microarray technology.
AB  - Agarose-coated glass slides, after activation, were spotted with amine-modified
      oligonucleotide probes using a manual eight-pin arraying device. Two probes,
      designed to identify two common greenhouse fungal plant pathogens, Didymella
      bryoniae and Botrytis cinerea, were hybridized with polymerase chain reaction
      (PCR)-amplified fluorescently labeled DNA extracted from pure culture and from
      diseased plant tissue. The probes easily distinguished these pathogens from each
      other without cross reaction. Thickness of the agarose layer and length of the
      sample DNA were important factors affecting hybridization efficiency of
      immobilized probe to PCR product. These factors did not affect hybridization with
      short complementary oligonucleotide. Probes fixed on agarose-coated slides could
      differentiate samples as readily as probes on nylon but with potentially higher
      spot density and gave much better signal than probes on silylated slides. The use
      of plain glass slides, agarose, and a manual arrayer makes this technique useful
      for developing specialized and inexpensive DNA microarrays on a solid rigid
      substrate.

PMID- 15958186
TI  - A continuous spectrophotometric assay for human cystathionine beta-synthase.
AB  - We report a new continuous spectrophotometric assay for human cystathionine beta
      synthase (hCBS). This assay relies upon the finding that hCBS will take
      cysteamine in place of L-homocysteine, thereby producing thialysine. Thialysine
      is, in turn, decarboxylated by lysine decarboxylase, releasing CO2 that is
      monitored by the sequential action of phosphoenolpyruvate carboxylase and L
      malate dehydrogenase. The decrease in absorbance at 340 nm is monitored as
      reduced nicotinamide adenine dinucleotide is consumed. Using this four-enzyme
      couple, we find that Km(app) = 1.2+/-0.2 mM for L-serine and 5.6+/-2.2 mM for
      cysteamine, with kcat = 1.3+/-0.1s(-1) for the formation of thialysine by hCBS.
      For comparison purposes, the same hCBS reaction was monitored via a radioactive
      single time point assay using 14C-(C-1)-labeled L-serine and cysteamine as
      substrates, counting the thialysine product, following ion exchange
      chromatography. This assay yielded Km(app) = 2.2+/-0.5 mM for L-serine and 6.6+/
      2.2 for cysteamine, with kcat = 2.5+/-0.4 s(-1). These numbers indicate that,
      although it possesses a shortened carbon chain and lacks a carboxyl group,
      cysteamine displays a catalytic efficiency (kcat/Km) with hCBS that is within an
      order of magnitude of that observed with its natural thiol cosubstrate, L
      homocysteine.

PMID- 15958188
TI  - The removal of pyroglutamic acid from monoclonal antibodies without denaturation
      of the protein chains.
AB  - Typically, the removal of pyroglutamate from the protein chains of
      immunoglobulins with the enzyme pyroglutamate aminopeptidase requires the use of
      chaotropic and reducing agents, quite often with limited success. This article
      describes a series of optimization experiments using elevated temperatures and
      detergents to denature and stabilize the heavy chains of immunoglobulins such
      that the pyroglutamate at the amino terminal was accessible to enzymatic removal
      using the thermostable protease isolated from Pyrococcus furiosus. The detergent
      polysorbate 20 (Tween 20) was used successfully to facilitate the removal of
      pyroglutamate residues. A one-step digestion was developed using elevated
      temperatures and polysorbate 20, rather than chaotropic and reducing agents, with
      sample cleanup and preparation for Edman sequencing performed using a commercial
      cartridge containing the PVDF membrane. All of the immunoglobulins digested with
      this method yielded heavy chain sequence, but the extent of deblocking was
      immunglobulin dependent (typically>50%).

PMID- 15958187
TI  - Homogeneous assays for cellular proteases employing the platinum(II)
      coproporphyrin label and time-resolved phosphorescence.
AB  - Phosphorescent platinum(II) coproporphyrin label (PtCP) is evaluated for the
      detection of cellular proteases by time-resolved fluorescence in homogeneous
      format. An octameric peptide containing the recognition motif for the caspase-3
      enzyme was dual labeled with a new maleimide derivative of PtCP and with the dark
      quencher dabcyl. Following photophysical characterization, the quenched substrate
      was employed in cleavage assays for caspase-3 using Jurkat and HL60 cell lines
      treated with proapoptotic stimuli performed on a commercial plate reader. Dose
      response and time course assays for the drug camptothecin were obtained for
      comparison with conventional fluorometric detection.

PMID- 15958189
TI  - Monitoring the acetohydroxy acid synthase reaction and related carboligations by
      circular dichroism spectroscopy.
AB  - Acetohydroxy acid synthase (AHAS) and related enzymes catalyze the production of
      chiral compounds [(S)-acetolactate, (S)-acetohydroxybutyrate, or (R)
      phenylacetylcarbinol] from achiral substrates (pyruvate, 2-ketobutyrate, or
      benzaldehyde). The common methods for the determination of AHAS activity have
      shortcomings. The colorimetric method for detection of acyloins formed from the
      products is tedious and does not allow time-resolved measurements. The continuous
      assay for consumption of pyruvate based on its absorbance at 333 nm, though
      convenient, is limited by the extremely small extinction coefficient of pyruvate,
      which results in a low signal-to-noise ratio and sensitivity to interfering
      absorbing compounds. Here, we report the use of circular dichroism spectroscopy
      for monitoring AHAS activity. This method, which exploits the optical activity of
      reaction products, displays a high signal-to-noise ratio and is easy to perform
      both in time-resolved and in commercial modes. In addition to AHAS, we examined
      the determination of activity of glyoxylate carboligase. This enzyme catalyzes
      the condensation of two molecules of glyoxylate to chiral tartronic acid
      semialdehyde. The use of circular dichroism also identifies the product of
      glyoxylate carboligase as being in the (R) configuration.

PMID- 15958190
TI  - A multiplex quantitation method for eicosanoids and platelet-activating factor
      using column-switching reversed-phase liquid chromatography-tandem mass
      spectrometry.
AB  - Eicosanoids and platelet-activating factor (PAF) are phospholipid-derived lipid
      mediators produced by various tissues and cells through a cascade pathway. For a
      comprehensive analysis of these lipid mediators, a simultaneous quantitation
      method with sensitivity and reliability is necessary. This article details a
      development of column-switching reversed-phase liquid chromatography-tandem mass
      spectrometry for multiplex quantitation of eicosanoids and PAF. The adsorptive
      nature of lipids caused significant loss of signal in a conventional column
      switching configuration. The use of an online-dilution method allowed use of 100%
      methanol as a sample solvent, which prevented sample adsorption to contacting
      surfaces. Addition of 0.2% formic acid to the sample solvent was required for the
      successful introduction of LTC4 to the trapping column and minimizing its
      carryover. The optimized method provided rapid analysis of 14 lipid mediators
      with a throughput of 96 samples/24 h, lower limits of quantitation of 5 pg on
      column, and linear calibration ranges up to 2000-5000 pg. The system was highly
      compatible with solid-phase-extracted samples, as methanol-eluted fractions were
      directly injected without reconstitution. The analysis of lipid mediator
      production of macrophage-like RAW264.7 cells demonstrated that the cell-based
      assay can be performed in a 96-well format, suitable for metabolomics analyses
      and/or screening strategies.

PMID- 15958191
TI  - Biochemical and cell-based assays for characterization of BACE-1 inhibitors.
AB  - The deposition of beta-amyloid peptides (A beta42 and A beta40) in neuritic
      plaques is one of the hallmarks of Alzheimer's disease (AD). A beta peptides are
      derived from sequential cleavage of amyloid precursor protein (APP) by beta- and
      gamma-secretases. BACE-1 has been shown to be the major beta-secretase and is a
      primary therapeutic target for AD. In this article, two novel assays for the
      characterization of BACE-1 inhibitors are reported. The first is a sensitive 96
      well HPLC biochemical assay that uses a unique substrate containing an optimized
      peptide cleavage sequence, NFEV, spanning from the P2-P2' positions This
      substrate was processed by BACE-1 approximately 10 times more efficiently than
      was the widely used substrate containing the Swedish (NLDA) sequence. As a
      result, the concentration of the enzyme required for the assay can be as low as
      100 pM, permitting the evaluation of inhibitors with subnanomolar potency. The
      assay has also been applied to related aspartyl proteases such as cathepsin D
      (Cat D) and BACE-2. The second assay is a homogeneous electrochemiluminescence
      assay for the evaluation of BACE-1 inhibition in cultured cells that assesses the
      level of secreted amyloid EV40_NF from HEK293T cells stably transfected with APP
      containing the novel NFEV sequence. To illustrate the use of these assays, the
      properties of a potent, cell-active BACE-1 inhibitor are described.

PMID- 15958192
TI  - Intracellular monitoring of superoxide dismutase expression in an Escherichia
      coli fed-batch cultivation using on-line disruption with at-line surface plasmon
      resonance detection.
AB  - An on-line cell disruption system for at-line monitoring of the intracellular
      concentration of recombinant human superoxide dismutase (rhSOD) in a genetically
      modified Escherichia coli strain, HMS174(DE3) (pET11a/rhSOD), in bioreactor
      cultivations is described. The sampled bacteria were disrupted on-line by rapid
      mixing with a nonionic detergent. The recombinant protein content of the lysed
      bacterial sample was quantitated by a subsequent surface plasmon resonance
      biosensor with a specific monoclonal antibody. Extraction efficiency of the
      monitoring system was optimized with respect to the flow rate ratio of the cell
      suspension and the detergent at relevant cell densities with the aim to attain
      rapid monitoring. Monitoring was demonstrated for a shake flask culture and a
      glucose-limited fed-batch cultivation. The results are compared with a
      traditional enzyme-linked immunosorbent assay method showing a correlation
      coefficient of R2 = 0.97. Extraction efficiency of rhSOD reached 95-99% at a
      total processing time of 1.8-2.6 min and a contact time of 0.8-1.4 min. The
      possibility of extending the monitoring system to other intracellular proteins is
      discussed.

PMID- 15958193
TI  - Rapid desalting of protein samples for on-line microflow electrospray ionization
      mass spectrometry.

PMID- 15958194
TI  - Batchwise covalent immobilization of human acetylcholinesterase: kinetic and
      inhibition spectrophotometric studies.

PMID- 15958195
TI  - Differentiation between amplicon polymerization and nonspecific products in SYBR
      green I real-time polymerase chain reaction.

PMID- 15958196
TI  - An assay for N-glycosylase activity on single-stranded DNA using stable,
      nonhazardous reagents.

PMID- 15958197
TI  - Chip surface charge switch for studying histone-DNA interaction by surface
      plasmon resonance biosensor.

PMID- 15958198
TI  - Microplate-based carboxymethylcellulose assay for endoglucanase activity.

PMID- 15958199
TI  - Effects of sodium fluoride on the actin cytoskeleton of murine ameloblasts.
AB  - Fluoride is associated with a decrease in the incidence of dental caries, but
      excess fluoride can lead to enamel fluorosis, a defect that occurs during tooth
      enamel formation. In fibroblasts, the Arhgap gene encodes a RhoGAP, which
      regulates the small G protein designated RhoA. Fluoride treatment of fibroblasts
      inactivates RhoGAP, thereby activating RhoA, which leads to elevation of
      filamentous actin (F-actin). Since RhoA is a molecular switch, our hypothesis is
      that in ameloblasts, fluoride may alter the cytoskeleton through interference
      with the Rho signaling pathway. Our objective was to measure the effects of
      sodium fluoride on F-actin using tooth organ culture and confocal microscopy. The
      results indicated that cellular responses to fluoride include elevation of F
      actin in ameloblasts. It was concluded from immunohistochemistry, RT-PCR and
      confocal approaches that the components of the Rho pathway are present in
      ameloblasts, and that the response to fluoride involves the Rho/ROCK pathway.

PMID- 15958200
TI  - Characterization of human primary enamel organ epithelial cells in vitro.
AB  - Tooth enamel is formed by ameloblasts, which are derived from the epithelial
      cells of the enamel organ. OBJECTIVE: The purpose of this study was to grow human
      ameloblast-like epithelial cells in culture. DESIGN: Human fetal tooth organs
      were isolated, and the cells were separated by digestion in collagenase/dispase.
      The cells were cultured in KGM-2 media with and without serum and at different
      calcium concentrations. The expression of enamel matrix proteins was analyzed by
      RT-PCR and cytokeratin 14 was detected by immunohistochemistry. The cells were
      further characterized by osteogenesis/odontogenesis-related DNA array. RESULTS:
      Cells isolated from the tooth organs grown in KGM-2 media containing 2-10% serum,
      were mixture of cobblestone and spindle shaped cells. Culturing these cells in
      KGM-2 with 0.05 mM calcium was selective for cobblestone ameloblasts-like cells
      (CAB), which were immunopositive for cytokeratin 14. Amelogenin, ameloblastin,
      enamelin, MMP-20 and KLK-4 were detected in CAB cells by RT-PCR. Osteogenesis
      SuperArray analyses could not detect the presence of typical molecules related to
      mesenchymal odontoblast or osteoblast lineage cells in these cultures.
      CONCLUSIONS: These studies showed that cobblestone-shaped ameloblast-like cells
      are selected from the tooth organ cells, by culture in KGM-2 media with 0.05 mM
      calcium.

PMID- 15958201
TI  - In vitro differentiation of dental epithelial progenitor cells through epithelial
      mesenchymal interactions.
AB  - In developing teeth, dental epithelial progenitor cells differentiate through
      sequential and reciprocal interactions with neural-crest-derived mesenchyme.
      However, the molecular mechanisms involved in cell differentiation are not well
      understood. Continuously growing teeth are useful in the study of differentiation
      of dental progenitor cells. In rat lower incisors, ameloblasts originate from the
      dental epithelial adult stem cell compartment referred to as the 'apical bud'. To
      elucidate the mechanism of ameloblast differentiation, we designed a primary
      culture system and confirmed the differentiation of dental epithelial cells
      through interaction with mesenchymal cells. Cytokeratin was used as a marker for
      epithelial cells, nerve growth factor receptor p75 for inner enamel epithelial
      (IEE) cells, and ameloblastin for ameloblasts. The apical bud cells could only
      differentiate into IEE cells and, within 10 days, into ameloblasts expressing
      ameloblastin in the presence of dental papilla cells. Interestingly, the IEE
      cells could proliferate transiently and differentiate into ameloblasts in the
      presence or absence of dental papilla cells. These results suggest that apical
      bud cells can enter the ameloblast cell lineage through interaction with
      mesenchymal cells. IEE cells, on the other hand, are already committed to
      differentiate into ameloblasts. This culture system is useful in future studies
      of ameloblast differentiation.

PMID- 15958202
TI  - Outward fluid flow reduces inward diffusion of bacterial lipopolysaccharide
      across intact and demineralised dentine.
AB  - OBJECTIVE: To examine the ability of outward fluid flow (OF) on resisting the
      inward diffusion of bacterial lipopolysaccharide (LPS) across the demineralised
      dentine (DD) in comparison with that across the intact dentine (ID). DESIGN:
      Twenty ID discs were prepared from freshly extracted human third molars. After
      etching both dentine surfaces, hydraulic conductance (L(p)) of the dentine was
      measured. Ten dentine discs were then completely demineralised using 10% EDTA,
      and L(p) was re-measured. The diffusion of LPS through ID and DD was measured
      against the OF and compared to the non-outward flow (NF) (n = 5 for each group)
      at 0, 1, 4 and 8h. Longitudinal sections of ID and DD surfaces were observed
      under a scanning electron microscope (SEM). RESULTS: The L(p) of DD was
      significantly higher than that of ID (independent t-test, p < 0.001). The
      application of OF and demineralisation significantly affected LPS diffusion (two
      way ANOVA, p < 0.05). In addition, the effect of OF depended on dentine
      demineralisation. SEM images of ID showed intact dentinal tubules, whereas those
      of DD showed expanded collagen fibres and enlarged dentinal tubules. CONCLUSIONS:
      The inward diffusion of LPS across DD differed from that of ID and the OF
      affected the inward diffusion of LPS. In the presence of the OF, the inward
      diffusion of LPS was reduced to near zero in both ID and DD. Nevertheless, when
      compared to that in the ID group, the OF produced the slightly greater effect to
      resist the inward LPS diffusion in the DD group.

PMID- 15958203
TI  - Distributions of magnesium and sulphur in defect layers of incisor dentine in
      magnesium-deficient rats.
AB  - This study examined the mechanism governing the occurrence of defect layers of
      incisor dentine in Mg-deficient rats by X-ray microanalysis. Young (5 weeks of
      age) Wistar male rats were pair-fed semi-synthetic diets containing either
      control (0.05% Mg) (N = 8) or Mg-deficient (0.001% Mg) (N = 8) ingredients for 17
      days. All animals were time marked with a combination of 0.1 mol
      nitrilotriacetato lead and 0.1 mol nitrilotriacetato zinc (2mg Pb/kg body weight)
      on days 0, 7 and 14 into incisor dentine. Blood samples were obtained on days 10
      and 17 in order to measure Ca, Mg, P and alkaline phosphatase activity levels in
      serum; moreover, hypomagnesaemia and hypercalcaemia were confirmed. After the
      17th day, rats were sacrificed humanely under anaesthesia and mandibular incisors
      were removed. Dentine formation of right mandibular incisors was assessed (time
      marking lines); furthermore, Ca, P, Mg and sulphur (S) concentrations as well as
      Ca/P molar ratio were determined in left mandibular incisors based on contiguous
      measurement points at 2 microm intervals from dentine pulp to dentine of the
      lingual aspect via X-ray analysis. Additionally, proteoglycan distribution was
      observed in other Mg-deficient rat dentine. These findings demonstrated decreases
      in body weight, incisor formation and incisor length in Mg-deficient rats. Mg and
      S levels increased in the defect layers, whereas proteoglycan decreased. This
      phenomenon was possibly attributable to condensation of Mg and S contents
      consequent to decreased dentine formation during Mg-deficiency and a transient
      increase in Mg due to transport of Mg as a result of inhibition of cell
      proliferation in soft tissues.

PMID- 15958204
TI  - Fatigue-related changes in discharge patterns of motor units in the inferior head
      of the lateral pterygoid muscle in humans.
AB  - OBJECTIVE: To investigate single motor unit (SMU) firing patterns of the inferior
      head of the human lateral pterygoid muscle (IHLP) during sustained isometric
      contractions, and to examine IHLP fatigability. DESIGN: In 5 subjects, EMG was
      recorded from the right IHLP during generation of horizontal isometric mandibular
      force towards left side. Subjects tracked a target on an oscilloscope, slowly
      increasing the force to 25% of maximum voluntary contraction, and then maintained
      that force for 120 s (endurance task). Subjects rested for 30 s after each test,
      and three 10s recovery tests were performed every 30 s (recovery task). Fatigue
      data were obtained from 23 SMUs. RESULTS: Twelve of 23 SMUs (52.2%) continued to
      fire throughout the 120 s, and each subject had at least one of these units.
      These units were classified as tonic pattern (T-unit). The firing rate of 6 of
      the 12 T-units (50.0%) decreased gradually with time. Comparison of the mean
      firing rate and coefficient of variance (CV) of interspike interval (ISI) of the
      12 T-units between pre-fatigue, post-fatigue and the three recovery tasks showed
      that the mean firing rate decreased and CV of ISI increased after fatigue. Mean
      firing rate and CV of ISI recovered after 30 s of rest after the endurance task.
      CONCLUSIONS: The firing patterns of IHLP units changed with the passing of time
      during sustained isometric contractions leading to fatigue.

PMID- 15958205
TI  - The influence of product and oral characteristics on swallowing.
AB  - The urge to swallow food could be triggered by a threshold level in both food
      particle size and lubrication of the food bolus. Thus, both oral physiology and
      product characteristics may influence the swallowing threshold. We quantified the
      swallowing threshold in a group of 266 healthy adult subjects (age 42 +/- 12
      years) by counting the number of chewing cycles needed to prepare food for
      swallowing. The influence of oral physiology on the swallowing threshold was
      determined by measuring salivary flow rate, maximum bite force and masticatory
      performance. We used about 10 cm(3) of bread, toast, melba toast, breakfast cake,
      peanuts and cheese to determine the influence on the swallowing threshold of
      various food characteristics, e.g. hardness, moisture and fat. Furthermore, we
      tested the effect of buttering the bread, toast, melba toast and breakfast cake
      on the swallowing threshold. Salivary flow rates were significantly and
      negatively correlated with the number of chewing cycles of melba toast and
      breakfast cake. Hence, subjects with more saliva needed less chewing cycles for
      these dry products. Maximum bite force and masticatory performance had an
      influence on the swallowing threshold for the hard products only (carrot and
      peanut). Although significant, the correlation coefficients were less than 0.28.
      Thus, the oral physiology parameters explained less than 10% of the variance in
      the swallowing threshold. We found significantly different numbers of chewing
      cycles for the various foods, ranging from 17 for cake to 63 for carrot. Hard and
      dry products needed more chewing cycles until swallowing. Buttering the food
      significantly reduced the number of chewing cycles needed before swallowing. This
      was especially true for the dry products cake, melba toast and toast. Hard and
      dry products require more chewing cycles and longer time in mouth until
      swallowing for sufficient breakdown to take place and for enough saliva to be
      added to form a coherent bolus safe for swallowing. In spite of this, more
      saliva, higher maximum bite force and better masticatory performance were only
      weakly correlated with a smaller number of chewing cycles. Butter enhanced
      lubrication and bolus formation of dry products, thus reducing the number of
      chewing cycles until swallowing. In conclusion, product characteristics and to a
      lesser extent oral physiology significantly affect swallowing threshold.

PMID- 15958206
TI  - Multi-target antimicrobial actions of zinc against oral anaerobes.
AB  - OBJECTIVE: Zinc is used in oral care products as an antiplaque/antigingivitis
      agent. Our objective was to assess the antimicrobial actions of zinc against oral
      anaerobes associated with gingivitis, specifically Fusobacterium nucleatum and
      Prevotella intermedia, with focus on catabolism and oxidative metabolism.
      METHODS: The oral anaerobes were grown in complex medium in an anaerobic chamber,
      harvested by centrifugation and used directly for experiments with suspensions.
      Biofilm growth involved super-infection by F. nucleatum of an initial biofilm
      formed by Streptococcus sanguis. RESULTS: Zn(2+) inhibited catabolism of
      glutamate, glutamyl-glutamate, glucose and fructose by F. nucleatum cells in
      suspensions with ID(50) values, respectively, of 0.05, 0.005, 0.01 and 0.01 mM.
      The ID(50) value for inhibition of glutamate catabolism by biofilms was 0.10 mM.
      Inhibition of glutamate catabolism could be related to inhibition of substrate
      uptake and of 2-oxoglutarate reductase. Zn(2+) also inhibited catabolism of
      aspartate or aspartyl-aspartate by P. intermedia with ID(50) values of 0.07 and
      about 0.03 mM, respectively. Respiration of intact cells of F. nucleatum and NADH
      oxidase in cell extracts were sensitive to zinc with ID(50) values, respectively,
      of about 1.0 and 1.4 mM. Zinc also inhibited production of hydrogen peroxide by
      F. nucleatum (ID(50) = ca. 0.04 mM.) but at high concentrations acted to
      potentiate and enhance peroxide killing of the anaerobe. CONCLUSION: Zn(2+) is a
      potent inhibitor of catabolism by F. nucleatum and P. intermedia, including
      catabolism of peptides, which can be degraded to yield inflammatory metabolic end
      products. Zn(2+) also inhibits O(2) metabolism of F. nucleatum by about 50% and
      hydrogen peroxide production nearly completely but also enhances killing by
      peroxide added to cells.

PMID- 15958207
TI  - Modeling directed ligand passage toward enzyme active site by a 'double cellular
      automata' model.
AB  - It is recently proposed that directed passage of ligand on the surface of enzymes
      may play an important role in the process of enzyme activity, as a result of
      decreasing the required steps of random walking of the ligand toward the active
      site. Here, we revisited the approach applied by others, where a cellular
      automaton is designed to simulate the behavior of a ligand molecule traveling
      toward the active site of an enzyme. Since a cellular automaton plane is
      topologically equivalent to a torus surface, we recommended the use of a 'double
      cellular automata' to model globular proteins. With the boundary conditions
      applied, our model is topologically identical to a sphere. It was shown that
      using this model, even fewer steps are needed for a molecule to attend the active
      site. This assumption can lead to more realistic results in the modeling of
      surfaces with spherical topology.

PMID- 15958208
TI  - Low "penetrance" of phylogenetic knowledge in mitochondrial disease studies.
AB  - An up-to-date view of the worldwide mitochondrial DNA (mtDNA) phylogeny together
      with an evaluation of the conservation of each site is a reliable tool for
      detecting errors in mtDNA studies and assessing the functional importance of
      alleged pathogenic mutations. However, most of the published studies on
      mitochondrial diseases make very little use of the phylogenetic knowledge that is
      currently available. This drawback has two inadvertent consequences: first, there
      is no sufficient a posteriori quality assessment of complete mtDNA sequencing
      efforts; and second, no feedback is provided for the general mtDNA database when
      apparently new mtDNA lineages are discovered. We demonstrate, by way of example,
      these issues by reanalysing three mtDNA sequencing attempts, two from Europe and
      another one from East Asia. To further validate our phylogenetic deductions, we
      completely sequenced two mtDNAs from healthy subjects that nearly match the
      mtDNAs of two patients, whose sequences gave problematic results.

PMID- 15958209
TI  - Effects of Gas6 and hydrogen peroxide in Axl ubiquitination and downregulation.
AB  - The receptor tyrosine kinase Axl has been shown to be activated by its ligand
      Gas6 and by oxidative stress in the form of hydrogen peroxide. However, the
      regulatory mechanisms controlling the levels of Axl upon Gas6 binding or
      oxidative stress have not been elucidated. This report demonstrates that Gas6
      induced downregulation of Axl is blocked by inhibitors of endocytosis and
      lysosomal degradation, but not by inhibitors of proteosomal activity.
      Furthermore, it is shown that binding of Axl to Gas6 induces the phosphorylation
      and ubiquitination of Axl and the interaction of Axl with the ubiquitin ligase c
      Cbl. Importantly, hydrogen peroxide induces Axl tyrosine phosphorylation but not
      its ubiquitination, determining the inhibition of Axl downregulation. These
      results suggest that as shown for other receptor tyrosine kinases, ubiquitination
      of Axl is needed to ensure its proper degradation in the lysosome, and that
      oxidative stress may inhibit Axl ubiquitination and downregulation.

PMID- 15958210
TI  - Cleavage of carcinoembryonic antigen induces metastatic potential in colorectal
      carcinoma.
AB  - Carcinoembryonic antigen (CEA), a widely used tumor marker, is attached by a
      glycosylphosphatidylinositol (GPI) anchor motif to the cell membrane. Recent
      study suggested that membrane-bound CEA might be cleaved by
      glycosylphosphatidylinositol-phospholipase D (GPI-PLD). We studied the effect of
      GPI-PLD on the cleavage of CEA to elucidate the implication for metastatic
      potential in colorectal carcinoma cells. CEA amount of conditioned medium was
      changed by suramin and phenanthroline (activator and inhibitor of GPI-PLD) only
      in SW620 and SW837 which expressed both CEA and GPI-PLD mRNA. Suramin treatment
      also augmented migratory activity and decreased cell surface CEA expression in
      SW620 and SW837. Furthermore, GPI-PLD knockdown cells using GPI-PLD-specific
      siRNA in SW620 and SW837 showed decreased CEA secretion from cell membrane and
      the migration activity, increased membrane-bound CEA amount. Splenic injection of
      SW620 and SW837 induced marked hepatic metastases in nude mice. These results
      suggest that membrane-bound CEA is cleaved by GPI-PLD and that this cleavage
      enhances the metastatic potential in colorectal carcinoma cells.

PMID- 15958211
TI  - Prosthetic heart valves' mechanical loading of red blood cells in patients with
      hereditary membrane defects.
AB  - Implantable cardiovascular devices such as prosthetic heart valves (PHVs) are
      widely applied clinical tools. Upon implantation, the patient can suffer from
      anemia as a result of red cell destruction and hemolysis can be more relevant
      whenever the patient is also affected by red cell disorders in which erythrocytes
      are more susceptible to mechanical stress such as hereditary spherocytosis (HS)
      and hereditary elliptocytosis (HE). Considering the typical morphological
      alterations observed in HS and HE, a study of the influence of cell geometry on
      the distribution of the shear stress on red cells in biological fluids was
      carried out. A numerical simulation of the loading caused by Reynolds shear
      stresses on a prolate spheroid was performed, with the ellipticity of the
      particle as the independent parameter. The average shear stress on a particle in
      the blood stream was found to depend on the particle's geometry, besides the
      stress field produced by the prosthetic device. The relevance of an increasing
      particle ellipticity on the global load is discussed. The model was applied to
      erythrocytes from implanted patients with HE or HS, enabling to explain the
      occurrence of moderate or severe anemia, respectively. The clinical data support
      the relevance of the proposed global parameter as erythrocyte trauma predictor
      with regard to the fluid dynamics of artificial organs.

PMID- 15958212
TI  - Changes in interface pressures and shear stresses over time on trans-tibial
      amputee subjects ambulating with prosthetic limbs: comparison of diurnal and six
      month differences.
AB  - For trans-tibial amputees maintenance over time of a quality fit of the
      prosthesis to the residual limb is an important clinical challenge. The purpose
      of this research was to compare diurnal and long-term (5 weeks to 6 months)
      interface stress changes as well as variance in the change in cross-sectional
      area down the length of the residual limb. If long-term changes were simply
      accentuated diurnal fluctuations then this result would suggest similar treatment
      methods should be used for both conditions. Interface pressures and shear
      stresses at 13 sites and residual limb shape were measured on eight trans-tibial
      amputee subjects using patellar-tendon-bearing prostheses. Data were collected at
      diurnal intervals (within the same day at least 5 h apart) as well as at long
      term intervals (5, 10, 15, 20, and 25 weeks apart). Absolute diurnal interface
      stress changes were not significantly different from those at 5-weeks intervals
      but were significantly smaller than those at 15, 20, and 25-weeks intervals. Mean
      interface stress changes increased significantly (p<0.05) for increased session
      to-session intervals. Variance of the change in cross-sectional area down the
      length of the residual limb was significantly smaller for diurnal intervals than
      for 6-months intervals, indicating that long-term changes were more localized
      than diurnal changes. These results indicate that long-term changes are not
      simply accentuated diurnal fluctuations, suggesting that different treatment
      methods should be used to treat each condition.

PMID- 15958213
TI  - Cardiovascular stent design and vessel stresses: a finite element analysis.
AB  - Intravascular stents of various designs are currently in use to restore patency
      in atherosclerotic coronary arteries and it has been found that different stents
      have different in-stent restenosis rates. It has been hypothesized that the level
      of vascular injury caused to a vessel by a stent determines the level of
      restenosis. Computational studies may be used to investigate the mechanical
      behaviour of stents and to determine the biomechanical interaction between the
      stent and the artery in a stenting procedure. In this paper, we test the
      hypothesis that two different stent designs will provoke different levels of
      stress within an atherosclerotic artery and hence cause different levels of
      vascular injury. The stents analysed using the finite-element method were the S7
      (Medtronic AVE) and the NIR (Boston Scientific) stent designs. An analysis of the
      arterial wall stresses in the stented arteries indicates that the modular S7
      stent design causes lower stress to an atherosclerotic vessel with a localized
      stenotic lesion compared to the slotted tube NIR design. These results correlate
      with observed clinical restenosis rates, which have found higher restenosis rates
      in the NIR compared with the S7 stent design. Therefore, the testing methodology
      outlined here is proposed as a pre-clinical testing tool, which could be used to
      compare and contrast existing stent designs and to develop novel stent designs.

PMID- 15958214
TI  - Biomechanical assessment of stability in the metastatic spine following
      percutaneous vertebroplasty: effects of cement distribution patterns and volume.
AB  - Percutaneous vertebroplasty is a minimally invasive, radiologically guided
      procedure whereby bone cement is injected into structurally weakened vertebrae to
      provide added biomechanical stability. In addition to treating osteoporotic
      vertebral fractures, this technique is also used to relieve pain by stabilizing
      metastatically compromised vertebrae that are at risk of pathologic burst
      fracture. Optimal cement distribution patterns to improve biomechanical stability
      to metastatically involved vertebral bodies remain unknown. This study aimed to
      determine the effect of cement location and volume of cement injected during
      percutaneous vertebroplasty on improving vertebral stability in a metastatically
      compromised spinal motion segment using a parametric poroelastic finite element
      model. A three-dimensional parametric finite element model of a thoracic spinal
      motion segment was developed and analyzed using commercially available software.
      A total of 16 metastatic pre and post vertebroplasty scenarios were investigated
      using a serrated spherical representation of tumor tissue and various geometric
      representations of polymethylmethacrylate (PMMA). The effect of vertebroplasty on
      vertebral bulge, a measure of posterior vertebral body wall motion as an
      indicator of burst fracture initiation, was assessed. In all cases,
      vertebroplasty reduced vertebral bulge, but the risk of the initiation of burst
      fracture was minimized with cement located posterior to the tumor, near the
      posterior vertebral body wall. Vertebral bulge decreased by up to 62% with 20%
      cement injection. These findings demonstrate that location and distribution of
      cement within the vertebral body has a noticeable effect on the restoration of
      biomechanical stability following percutaneous vertebroplasty.

PMID- 15958215
TI  - Development and evaluation of an optimization-based model for power-grip posture
      prediction.
AB  - An optimization-based model for power-grip posture prediction was proposed. The
      model was based on the premise that the hand prehensile configuration in a power
      grip best conforms to the object shape. This premise was embodied by an
      optimization procedure that minimized the sum of distances from the finger joints
      to the object surface. The model was evaluated against data from an experiment
      that measured the grasp postures of 28 subjects having diverse anthropometry. The
      intra- and inter-person variabilities in grip postures were empirically assessed
      and used as benchmark values for model evaluation. The evaluation showed that the
      root-mean-square (RMS) values of angle differences between the predicted and
      measured postures had a 13.7 degrees grand mean (across all joints, subjects, and
      two cylindrical handles grasped), whereas the RMS values of the inter- and intra
      person variabilities in measured postures had grand means of 13.0 degrees and 4.4
      degrees , respectively. The model can be readily generalized to the prediction of
      postures in power-grasping objects of different shapes, and adapted for testing
      alternative prehensile strategies or performance criteria.

PMID- 15958216
TI  - Mechanics of scars.
AB  - When a wound heals, as everyone has observed, it contracts, thickens and wrinkles
      the neighbouring skin, forming a scar. The morphology of the scar depends on the
      type of wound; an urgent tracheotomy leads to a very different scar than a
      carefully planned face lift. The surgical challenges of intrusive procedures such
      as removal of skin lesions, skin transplantation or grafting, and scar removal
      are complicated by the complex geometry and stress states in different parts of
      the body. We show that, for relatively general conditions, the nature of the
      localisation of the scar is determined by the background tension of the skin
      which can arrest the formation of wrinkles around a scar. Our physical
      experiments to simulate this procedure indicate that the region deformed by the
      defect has a characteristic length scale r* approximately 1 square root of tau,
      where tau is the natural tension of the skin.

PMID- 15958217
TI  - A correction for axis misalignment in the joint angle curves representing knee
      movement in gait analysis.
AB  - This paper derives a simple mathematical model relating changes in the
      orientations of the two Cartesian coordinate systems involved in recording knee
      movement and the varus-valgus and the internal-external rotation angles for
      describing the knee's motion. Rotation matrices are given for changing the
      orientations of the two Cartesian coordinate systems in such a way that the
      quadratic variations in the varus-valgus and in the external-internal angles are
      minimal. These estimated rotation matrices are used to correct for axis
      misalignment. The correction is calibrated by considering the impact of the new
      orientation of the thigh Cartesian coordinate system on the hip joint angles. The
      procedure is applied to kinematic data collected on normal subjects. The
      uncertainty about the specification of the thigh Cartesian coordinate system is
      shown to explain some of the between subject variability in the varus-valgus and
      in the internal-external rotation angles curves.

PMID- 15958218
TI  - The application of topology optimization on the quantitative description of the
      external shape of bone structure.
AB  - The aim of this paper was to introduce the idea of topology optimization in
      engineering to the simulation of bone morphology. The external shape of bone
      structure was predicted with the quantitative bone functional adaptation theory.
      The high-order nonlinear equation of bone remodeling proposed by Zhu et al. (J.
      Biomech. 35(7)(2002)951) combining with the finite element method was adopted to
      a rectangular design domain, which occupies a larger space than the external
      shape of bone structure. It was at this point we imported the idea of topology
      optimization in engineering. The proximal femur was used here as an example,
      whose external shape and internal density distribution were simultaneously
      simulated quantitatively to validate that the external shape of bone structure
      could be successfully predicted in this way. Then the growth of vertebral body
      from young to old was simulated numerically in its coronal section to discuss the
      significance of the prediction of external shape. The study in this paper
      provides computational basis for further studies on osteophyte formation,
      osteoporosis, osteoarthritis, bone growth and even bone evolution, etc.

PMID- 15958219
TI  - Modulation of force transmission to the head while carrying a backpack load at
      different walking speeds.
AB  - This study was designed to investigate the capability of the joints and segments
      to reduce transmission of forces during load carriage. Eleven subjects were
      required to carry a backpack loaded with 40% of their body weight and to walk at
      6 speeds increasing from 0.6 to 1.6 ms(-1) in increments of 0.2 ms(-1), and then
      decreasing in the same manner. Subjects were filmed in 3-dimensions, but analysis
      of shock transmission ratio (TR) was limited to the sagittal plane. Shock
      transmission was measured as the ratio of peak vertical accelerations
      (ankle:head, ankle:knee, and knee:head) measured immediately following foot
      strike. TR for all ratios increased significantly as a function of increasing
      speed. TR from the ankle to the head showed no significant increase as a function
      of load carriage, but did increase as a function of load in transmission from
      knee to head. A significant interaction effect revealed that during load carriage
      at the higher speeds the acceleration of the ankle and knee decreased below that
      for the unloaded conditions. These findings suggest that the potentially
      injurious effects of previously observed increased ground reaction forces and
      increased joint stiffness while walking with loads are offset by adaptations in
      the gait pattern that maintain force transmission at acceptable levels. Increased
      variability in the acceleration of the head and in the transmission ratios
      suggest a potentially destabilizing effect of load carriage on the head
      trajectory.

PMID- 15958220
TI  - Evaluation of limb compartments with increased interstitial pressure. An improved
      noninvasive method for determining quantitative hardness.
AB  - The purpose of this project was to study a noninvasive method of evaluating limbs
      at risk of compartment syndrome. Untreated limb compartment syndrome may lead to
      irreversible dysfunction, chronic pain and contracture. An improved means of
      obtaining quantitative hardness measurements is reported. The handheld
      noninvasive compartment syndrome evaluator (NCSE) device formulates a
      quantitative hardness curve of force verse depth of indentation by applying a 5.0
      mm diameter indenter to a limb muscle compartment. Eighteen volunteers (9 men, 9
      women) had elevated intracompartmental interstitial pressures by application of
      custom-made tourniquets. Comparison of interstitial pressure to quantitative
      hardness measurements in 71 compartments tested showed a statistically
      significant strong linear relationship with an average Pearson correlation
      coefficient of .84 (range .78-.9 P<.0001). In addition, for all compartments
      tested, the mean hardness value for the group with interstitial pressure greater
      than 50 mmHg (considered compartment syndrome) was close to 2x greater and was
      statistically different than the mean hardness for the group with interstitial
      pressure less than 30 mmHg (no compartment syndrome, t-test: P<.0001). This study
      utilizes a device that has improved upon previous quantitative hardness
      measurement techniques. In addition, by utilizing a tourniquet model to create
      elevated interstitial intracompartmental pressure in volunteers, data collection
      was easier and faster. In the future, quantitative hardness measurements may
      accurately predict interstitial intracompartmental pressure for most patients.
      This technique may greatly enhance the medical community's ability to diagnose
      compartment syndrome with a noninvasive means.

PMID- 15958221
TI  - Determining the effect of hydration upon the properties of ligaments using pseudo
      Gaussian stress stimuli.
AB  - The level of tissue hydration is known to effect viscoelastic material
      properties. However, prior studies have not fully investigated the effect of
      hydration on dynamic behavior nor compared the results of transient and dynamic
      behavior. The material properties of medial collateral rat knee ligaments were
      studied in relation to hydration, using (sequentially) 0.3 osmolar artificial
      interstitial fluid (AIF), solutions of AIF plus sucrose with osmolarity 1.05,
      1.80 or 2.55, and then AIF. In each solution, the complex compliance was
      determined as a function of frequency, and the creep response was measured.
      Complex compliance was determined from a constitutive model created by applying a
      0.4+/-0.2 MPa pseudo Gaussian (PGN) stress stimulus to the ligament. Dehydration
      caused a reduction in cross-sectional area that was linearly related to the
      osmolarity of the solution. Reductions of up to 52% were observed and were
      reversible upon rehydration. Dehydration caused a reduction in the creep rate
      that was not immediately recovered upon rehydration. The storage compliance was
      reduced by up to 50% with dehydration; these changes were reversed upon
      rehydration. The loss compliance and phase angle were not affected by
      dehydration. Transient and dynamic experiments examine different viscoelastic
      characteristics and both types of tests appear to be necessary to fully
      characterize the effects of hydration.

PMID- 15958222
TI  - Magnetic resonance imaging for in vivo assessment of three-dimensional patellar
      tracking.
AB  - We have developed a non-invasive measurement technique which can ultimately be
      used to quantify three-dimensional patellar kinematics of human subjects for a
      range of static positions of loaded flexion and assessed its accuracy. Knee
      models obtained by segmenting and reconstructing one high-resolution scan of the
      knee were registered to bone outlines obtained by segmenting fast, low-resolution
      scans of the knee in static loaded flexion. We compared patellar tracking
      measurements made using the new method to measurements made using Roentgen
      stereophotogrammetric analysis in three cadaver knee specimens loaded through a
      range of flexion in a test rig. The error in patellar spin and tilt measurements
      was less than 1.02 degrees and the error in lateral patellar shift was 0.88 mm.
      Sagittal plane scans provided more accurate final measurements of patellar spin
      and tilt, whereas axial plane scans provided more accurate measurements of
      lateral translation and patellar flexion. Halving the number of slices did not
      increase measurement error significantly, which suggests that scan times can be
      reduced without reducing accuracy significantly. The method is particularly
      useful for multiple measurements on the same subject because the high-resolution
      bone-models need only be created once; thus, the potential variability in
      coordinate axes assignment and model segmentation during subsequent measurements
      is removed.

PMID- 15958223
TI  - Ligament cells stretch-adapted on a microgrooved substrate increase intercellular
      communication in response to a mechanical stimulus.
AB  - An in vitro model was used to investigate the effect of mechanical stimuli on
      adaptation to load and calcium signaling in aligned medial collateral ligament
      cells (MCL). This model used a patterned silicone membrane to align the cells
      parallel with the direction of the microgrooves. Alignment created an
      architecture that simulated a degree of cell orientation in native ligament
      tissue. It was hypothesized that aligned ligament cells would be more efficient
      at calcium wave propagation than cells that were randomly oriented. It was
      further hypothesized that calcium wave propagation would be greater among cells
      that were both aligned and subjected to mechanical stretch compared to cells that
      were aligned but not stretched. Rat MCL cells were loaded with Fura-2AM, a
      calcium-binding dye, and mechanically indented using a micropipette tip. A ratio
      imaging fluorescence technique was used to quantitate the calcium (Ca2+)
      response. It was concluded that stretching ligament cells prior to stimulation
      increased their sensitivity to load and their ability to propagate a calcium
      wave. However, the ability of aligned cells to propagate this wave was not
      significantly different when compared to nonaligned cells. Treatment of cultures
      with inhibitors such as apyrase and suramin significantly reduced the number of
      cells recruited in the calcium response. Hence, it was concluded that ATP
      released from mechanically stimulated cells was a principal mediator responsible
      for the rise in intracellular calcium in ligament cells. Further, purinoceptor
      activation may amplify the signal to alert and recruit more cells in a response
      to mechanical stimulation.

PMID- 15958224
TI  - Effect of dynamic loading on the frictional response of bovine articular
      cartilage.
AB  - The objective of this study was to test the hypotheses that (1) the steady-state
      friction coefficient of articular cartilage is significantly smaller under
      cyclical compressive loading than the equilibrium friction coefficient under
      static loading, and decreases as a function of loading frequency; (2) the steady
      state cartilage interstitial fluid load support remains significantly greater
      than zero under cyclical compressive loading and increases as a function of
      loading frequency. Unconfined compression tests with sliding of bovine shoulder
      cartilage against glass in saline were carried out on fresh cylindrical plugs
      (n=12), under three sinusoidal loading frequencies (0.05, 0.5 and 1 Hz) and under
      static loading; the time-dependent friction coefficient mu(eff) was measured. The
      interstitial fluid load support was also predicted theoretically. Under static
      loading mu(eff) increased from a minimum value (mu(min)=0.005+/-0.003) to an
      equilibrium value (mu(eq)=0.153+/-0.032). In cyclical compressive loading tests
      mu(eff) similarly rose from a minimum value (mu(min)=0.004+/-0.002, 0.003+/-0.001
      and 0.003+/-0.001 at 0.05, 0.5 and 1 Hz) and reached a steady-state response
      oscillating between a lower-bound (mu(lb)=0.092+/-0.016, 0.083+/-0.019 and
      0.084+/-0.020) and upper bound (mu(ub)=0.382+/-0.057, 0.358+/-0.059, and 0.298+/
      0.061). For all frequencies it was found that mu(ub)>mu(eq) and
      mu(lb)<mu(eq)(p<0.05). Under cyclical compressive loading the interstitial fluid
      load support was found to oscillate above and below the static loading response,
      with suction occurring over a portion of the loading cycle at steady-state
      conditions. All theoretical predictions and most experimental results
      demonstrated little sensitivity to loading frequency. On the basis of these
      results, both hypotheses were rejected. Cyclical compressive loading is not found
      to promote lower frictional coefficients or higher interstitial fluid load
      support than static loading.

PMID- 15958225
TI  - A homogenization model of the annulus fibrosus.
AB  - The objective of this study was to use a homogenization model of the anisotropic
      mechanical behavior of annulus fibrosus (AF) to address some of the issues raised
      in structural finite element and fiber-reinforced strain energy models.
      Homogenization theory describes the effect of microstructure on macroscopic
      material properties by assuming the material is composed of repeating
      representative volume elements. We first developed the general homogenization
      model and then specifically prescribed the model to in-plane single lamella and
      multi-lamellae AF properties. We compared model predictions to experimentally
      measured AF properties and performed parametric studies. The predicted tensile
      moduli (E theta and E z) and their dependence on fiber volume fraction and fiber
      angle were consistent with measured values. However, the model prediction for
      shear modulus (G thetaz) was two orders of magnitude larger than directly
      measured values. The values of E theta and E z were strongly dependent on the
      model input for matrix modulus, much more so than the fiber modulus. These
      parametric analyses demonstrated the contribution of the matrix in AF load
      support, which may play a role when protoeglycans are decreased in disc
      degeneration, and will also be an important design factor in tissue engineering.
      We next compared the homogenization model to a 3-D structural finite element
      model and fiber-reinforced energy models. Similarities between the three model
      types provided confidence in the ability of these models to predict AF tissue
      mechanics. This study provides a direct comparison between the several types of
      AF models and will be useful for interpreting previous studies and elucidating AF
      structure-function relationships in disc degeneration and for functional tissue
      engineering.

PMID- 15958226
TI  - Mechanical and failure properties of single attached cells under compression.
AB  - Eukaryotic cells are continuously subjected to mechanical forces under normal
      physiological conditions. These forces and associated cellular deformations
      induce a variety of biological processes. The degree of deformation depends on
      the mechanical properties of the cell. As most cells are anchorage dependent for
      normal functioning, it is important to study the mechanical properties of cells
      in their attached configuration. The goal of the present study was to obtain the
      mechanical and failure properties of attached cells. Individual, attached C2C12
      mouse myoblasts were subjected to unconfined compression experiments using a
      recently developed loading device. The device allows global compression of the
      cell until cell rupture and simultaneously measures the associated forces. Cell
      bursting was characterized by a typical reduction in the force, referred to as
      the bursting force. Mean bursting forces were calculated as 8.7+/-2.5 microN at
      an axial strain of 72+/-4%. Visualization of the cell using confocal microscopy
      revealed that cell bursting was preceded by the formation of bulges at the cell
      membrane, which eventually led to rupturing of the cell membrane. Finite element
      calculations were performed to simulate the obtained force-deformation curves. A
      finite element mesh was built for each cell to account for its specific
      geometrical features. Using an axisymmetric approximation of the cell geometry,
      and a Neo-Hookean constitutive model, excellent agreement between predicted and
      measured force-deformation curves was obtained, yielding an average Young's
      modulus of 1.14+/-0.32 kPa.

PMID- 15958227
TI  - Evaluation of the intervertebral neck injury criterion using simulated rear
      impacts.
AB  - The Intervertebral Neck Injury Criterion (IV-NIC) is based on the hypothesis that
      intervertebral motion beyond the physiological limit may injure spinal soft
      tissues during whiplash, while the Neck Injury Criterion (NIC) hypothesizes that
      sudden changes in spinal fluid pressure may cause neural injury. Goals of the
      present study, using a biofidelic whole cervical spine model with muscle force
      replication, were to correlate IV-NIC with soft-tissue injury, determine the IV
      NIC injury threshold, and compare IV-NIC and NIC. Using a bench-top apparatus,
      rear-impacts were simulated at 3.5, 5, 6.5, and 8 g horizontal accelerations of
      the T1 vertebra. Pre- and post-whiplash flexibility tests measured the soft
      tissue injury threshold, i.e. significant increases in the intervertebral neutral
      zone (NZ) or range of motion (ROM) above corresponding baseline values. Extension
      IV-NIC peaks correlated well with NZ and ROM increases at C0-C1 and at C3-C4
      through C7-T1 (r=0.64 and 0.62 respectively, p<0.001). Average IV-NIC injury
      thresholds (95% confidence limits) varied among the intervertebral levels and
      ranged between 1.5 (1.1, 1.9) at C5-C6 and 3.4 (2.4, 4.4) at C7-T1. The NIC
      injury threshold was 8.7 (7.7, 9.7) m2/s2, substantially less than the proposed
      threshold of 15 m2/s2. Results support the use of IV-NIC for determining the
      cervical spine injury threshold and injury severity. Advantages of IV-NIC include
      the ability to predict the intervertebral level, mode, severity, and time of the
      cervical spine soft-tissue injury.

PMID- 15958228
TI  - Acromion-fixation of glenoid components in total shoulder arthroplasty.
AB  - Successful design of components for total shoulder arthroplasty has proven to be
      challenging. This is because of the difficulties in maintaining fixation of the
      component that inserts into the scapula; i.e., the glenoid component. Glenoid
      components that are fixated to both the glenoid and acromion (a long process
      extending medially on the dorsal aspect of the scapula) have the possible
      advantage of greater stability over those that are fixated to the glenoid alone.
      In this study, a finite element analysis is used to investigate whether or not
      acromion fixation is advantageous for glenoid components. Full muscle loading and
      joint reaction forces are included in the finite element model. Reflective
      photoelasticity of five scapulae is used to obtain experimental data to compare
      with results from the finite element analysis, and it confirms the structural
      behaviour of the finite element model. When implanted with an acromion-fixated
      prosthesis, it is found that high unphysiological stresses occur in the scapula
      bone, and that stresses in the fixation are not reduced. Very high stresses are
      predicted in that part of the prosthesis which connects the acromion to the
      glenoid. It is found that the very high stresses are partly in response to the
      muscle and joint reaction forces acting at the acromion. It is concluded that,
      because of the relatively high forces acting at the acromion, fixation to it may
      not be the way forward in glenoid component design.

PMID- 15958229
TI  - Multi-criterion optimization for heel-toe running.
AB  - This paper presents an optimization procedure for multi-criterion analysis
      essential in many biomechanical studies. The optimization is illustrated with a
      heel-toe running analysis wherein the rate of load and the passive load on
      support leg are minimized concurrently. The goal of multi-criterion optimization
      is achieved by incorporating the criterion of Pareto optimality in the genetic
      algorithm. The proposed procedure can replace the popular weighted-sum approach
      for problems with multiple objectives. The selection of a final design from the
      Pareto optimum points (non-dominated designs) can be determined, based on the min
      max objective deviation criterion. Nevertheless, a different decision can be made
      in the final selection without incurring recalculations. The scheme is readily
      adoptable for parallel computing, which deserves further study to reduce the
      execution time in a complex biomechanical analysis.

PMID- 15958230
TI  - Accuracy of WAAS-enabled GPS for the determination of position and speed over
      ground.
AB  - The Global Positioning System (GPS) offers many advantages over conventional
      methods for the determination of subject speed during biomechanical studies.
      Recent advances in GPS technology, in particular the implementation of the Wide
      Angle Augmentation System and European Geostationary Navigation Overlay Service
      (WAAS/EGNOS), mean that small, highly portable units are available offering the
      potential of superior accuracy in the determination of both position and speed.
      This study set out to examine the accuracy of a WAAS-enabled GPS unit for the
      determination of position and speed. Comparison with the new and published data
      showed significant enhancements in both position and speed accuracy over a non
      WAAS system. Position data collected during straight line cycling showed
      significantly lower sample-to-sample variation (mean absolute deviation from
      straight line 0.11 vs. 0.78 m) and greater repeatability from trial to trial
      (mean absolute deviation from actual path 0.37 vs. 4.8 m) for the WAAS-enabled
      unit compared to the non-WAAS unit. The speed determined by the WAAS-enabled GPS
      receiver during cycling in a straight line was within 0.2 ms(-1) of the actual
      speed measured for 57% of the values with 82% lying within 0.4 ms(-1), however,
      the data tended towards underestimation of speed during circle cycling, with 65%
      of values within 0.2 ms(-1) and 87% within 0.4 ms(-1) of the actual value. Local
      dGPS and dual frequency techniques are more accurate still, however, traditional
      differential GPS (dGPS), employing FM radio transmission of correction data to a
      separate receiver, now offers no advantage over WAAS and appears redundant.

PMID- 15958231
TI  - Soft tissue strain energy minimization: a candidate control scheme for intra
      finger normal-tangential force coordination.
AB  - The safety margin (SM) measure has been used to quantify the phenomenon that
      humans grasp objects more firmly than is necessary to prevent slip. The
      biomechanical basis for the SM phenomenon is addressed herein. A hypothesis is
      proposed regarding intra-finger normal-tangential force coordination. The idea is
      that the central nervous system (CNS) minimizes the strain energy of the soft
      finger pad tissue by varying normal force when presented with a certain
      tangential force. This control scheme requires no knowledge of the frictional
      conditions at the finger-object interface; the CNS needs only to detect the
      strain energy in the contact region, an area abundant with strain-sensitive
      mechanoreceptors. The scheme is not independent, but is rather a possible
      component of a more complicated system. The strain energy minimization problem
      was solved using the finite element model (FEM) of Wu et al. (Med. Eng. Phys.
      24(4)(2002) 253). Optimization results revealed that the suggested control scheme
      produced SM values of 30-50%, corresponding closely to those reported
      experimentally. Slip prevention naturally emerges from the control scheme
      provided that the friction coefficient exceeds 0.7, a value lower than typically
      encountered.

PMID- 15958232
TI  - Microtubules may harden or soften cells, depending of the extent of cell
      distension.
AB  - Experimental data show that disruption of microtubules causes cells to either
      become stiffer or softer. Current understanding of these behaviors is based on
      several different mechanisms, each of which can account for only stiffening or
      softening. In this study we offer a model that can explain both these features.
      The model is based on the cellular tensegrity idea. Key premises of the model are
      that cell shape stability is secured through pre-existing mechanical stress
      (prestress) borne by the actin cytoskeletal network, and that this prestress is
      partly balanced by cytoskeletal microtubules and partly by the extracellular
      matrix. Thus, disturbance of this balance would affect cell deformability. The
      model predicts that disruption of microtubules causes an increase or a decrease
      in cell stiffness, depending on the extent to which microtubules participate in
      balancing the prestress which, in turn, depends on the extent of cell spreading.
      In highly spread cells microtubules have a minor and negative contribution to
      cell stiffness, whereas in less spread cells their contribution is positive and
      substantial. Since in their natural habitat cells seldom exhibit highly spread
      forms, the above results suggest that the contribution of microtubules to cell
      deformability cannot be overlooked.

PMID- 15958233
TI  - The scapula is a sesamoid bone.

PMID- 15958235
TI  - Comments about the article titled: comparison of three methods to estimate the
      center of mass during balance assessment, written by D. Lafond, M. Duarte, F.
      Prince (37 (2004) 1421-1426).

PMID- 15958237
TI  - Comment on "an articular cartilage contact model based on real surface geometry",
      Han Sang-Kuy, Salvatore Federico, Marcelo Epstein and Walter Herzog, Journal of
      Biomechanics, 38 (2005) 179-184.

PMID- 15958239
TI  - Polyethylene oxide surfaces of variable chain density by chemisorption of PEO
      thiol on gold: adsorption of proteins from plasma studied by radiolabelling and
      immunoblotting.
AB  - The mechanisms involved in the inhibition of protein adsorption by polyethylene
      oxide (PEO) are not completely understood, but it is believed that PEO chain
      length, chain density and chain conformation all play a role. In this work,
      surfaces formed by chemisorption of PEO-thiol to gold were investigated: the
      effects of PEO chain density, chain length (600, 750, 2000 and 5000 MW) and end
      group (-OH, -OCH3) on protein adsorption from plasma are reported. Similar to
      previous single protein adsorption studies (L.D. Unsworth et al., Langmuir
      2005;21:1036-41) it was found that, of the different surfaces investigated, PEO
      layers formed from solutions near the cloud point adsorbed the lowest amount of
      fibrinogen from plasma. Layers of hydroxyl-terminated PEO of MW 600 formed under
      these low solubility conditions showed almost complete suppression (versus
      controls) of the Vroman effect, with 20+/-1 ng/cm2 adsorbed fibrinogen at the
      Vroman peak and 6.7+/-0.6 ng/cm2 at higher plasma concentration. By comparison,
      Vroman peak adsorption was 70+/-20 and 50+/-3 ng/cm2, respectively, for 750-OCH3
      and 2000-OCH3 layers formed under low solubility conditions; adsorption on these
      surfaces at higher plasma concentration was 16+/-9 and 12+/-3 ng/cm2. Thus in
      addition to the effect of solution conditions noted previously, the results of
      this study also suggest a chain end group effect which inhibits fibrinogen
      adsorption to, and/or facilitates displacement from, hydroxyl terminated PEO
      layers. Fibrinogen adsorption from plasma was not significantly different for
      surfaces prepared with PEO of molecular weight 750 and 2000 when the chain
      density was the same ( approximately 0.5 chains/nm2) supporting the conclusion
      that chain density may be the key property for suppression of protein adsorption.
      The proteins eluted from the surfaces after contact with plasma were investigated
      by SDS-PAGE and immunoblotting. A number of proteins were detected on the various
      surfaces including fibrinogen, albumin, C3 and apolipoprotein A-I. The blot
      responses were zero or weak for all four proteins of the contact system; some
      complement activation was observed on all of the surfaces studied.

PMID- 15958240
TI  - Compound changes and tooth mineralization effects of glass ionomer cements
      containing bioactive glass (S53P4), an in vivo study.
AB  - In this study, modifications of glass ionomer cements (GICs) were made by adding
      bioactive glass (BAG) to GIC to obtain bioactive restorative materials. This
      study used SEM, EDS and visual analysis to examine the bioactivity and the
      ability of the study materials to mineralize dentin. Conventional cure and resin
      modified light-curing GIC were used. The materials consisted of powder and
      liquid. Three experimental materials were made by mixing 10-30 wt% of BAG powder
      with GIC powders. Commercially available GIC without BAG were used as controls.
      Class III restorations were made in altogether 62 intact beagle dog teeth, and
      the operation was performed under general anesthesia. The restorations were
      followed clinically for 1, 3 or 6 weeks. Resin-modified GIC containing BAG showed
      uniform CaP surface formation on the restorations. Mineral depositions in the
      close vicinity of the restoration-dentin interface and in deeper parts of dentin
      tubules were also noticed in resin-modified GIC containing BAG particles. It can
      be concluded that resin-modified GIC containing BAG have good potential in
      clinical applications where enhanced mineralization is expected.

PMID- 15958241
TI  - Influence of anionic monomer content on the biodegradation and toxicity of
      polyvinyl-urethane carbonate-ceramic interpenetrating phase composites.
AB  - The objective of this study was to characterize a series of anionic biodegradable
      polymer resins for their compatibility in a biological environment, comparing
      them with respect to the influence of ionic function on enzyme catalyzed
      biodegradation when the polymers were incorporated into a porous calcium
      polyphosphate (CPP) 3-D structure to form an interpenetrating phase composite
      (IPC). The swelling behavior of the polymers was investigated by immersing the
      cured polymer resins in growth media at 37 degrees C. In vitro cytotoxicity of
      the polymer resins was assessed using a HeLa cell line. Cell viability increased
      when the amount of low molecular weight monomer was minimized. Despite observing
      that the addition of carboxylic acid groups into the polymer resin chains
      contributed to an improvement of the chemical bonding between the polymer and the
      CPP, the addition of high ionic content into the resin led to the greatest loss
      of bending strength for the samples incubated in phosphate buffer and cholesterol
      esterase enzyme solutions, when compared to their as made state. The increased
      degradation for the higher ionic component materials and their loss of physical
      strength was attributed to enhanced hydrolysis within the materials and by water
      transport deep within the composites, via the anionic components of the resin.
      The findings indicated that the introduction of anionic content must be optimized
      to promote increased mechanical performance for the CPP, balancing the features
      of polymer CPP bonding versus polymer swelling and cytotoxicity.

PMID- 15958242
TI  - Mechanical properties of gamma irradiated morselized bone during compaction.
AB  - This study examined the effects of gamma irradiation on the compressive
      properties of morselized cancellous bone from human femoral heads. Twelve bone
      samples, mean age of 68 years (range 92-39), were divided into 3 groups (N=12) of
      varying irradiation level (0, 15 and 25 kGy). Each specimen was compacted in a
      controlled fashion in steps of 0.5 mm at 0.5 mm/min (up 12 mm). The load and
      stiffness increased with compaction, but this relationship was not linear. There
      was no statistical significant difference in the compacting load or stiffness
      between groups (p>0.05) until the last 1 mm of compaction, where the 25 kGy group
      were significantly stiffer compared to controls but not different to the 15 kGy
      group. This may be due to decreased interlocking of bone particles caused by
      higher irradiation levels resulting in a stiffer graft.

PMID- 15958243
TI  - Injectable glycosaminoglycan hydrogels for controlled release of human basic
      fibroblast growth factor.
AB  - Synthetic hydrogel mimics of the extracellular matrix (ECM) were created by
      crosslinking a thiol-modified analog of heparin with thiol-modified hyaluronan
      (HA) or chondroitin sulfate (CS) with poly(ethylene glycol) diacrylate (PEGDA).
      The covalently bound heparin provided a crosslinkable analog of a heparan sulfate
      proteoglycan, thus providing a multivalent biomaterial capable of controlled
      release of basic fibroblast growth factor (bFGF). Hydrogels contained >97% water
      and formed rapidly in <10min. With as little as 1% (w/w) covalently bound heparin
      (relative to total glycosaminoglycan content), the rate of release of bFGF in
      vitro was substantially reduced. Total bFGF released increased with lower
      percentages of heparin; essentially quantitative release of bFGF was observed
      from heparin-free hydrogels. Moreover, the hydrogel-released bFGF retained 55% of
      its biological activity for up to 28 days as determined by a cell proliferation
      assay. Finally, when these hydrogels were implanted into subcutaneous pockets in
      Balb/c mice, neovascularization increased dramatically with HA and CS hydrogels
      that contained both bFGF and crosslinked heparin. In contrast, hydrogels lacking
      bFGF or crosslinked heparin showed little increase in neovascularization. Thus,
      covalently linked, heparin-containing glycosaminoglycan hydrogels that can be
      injected and crosslinked in situ constitute highly promising new materials for
      controlled release of heparin-binding growth factors in vivo.

PMID- 15958244
TI  - A continuous damage random thresholds model for simulating the fracture behavior
      of nacre.
AB  - This study investigates the fracture properties of nacre using a discrete lattice
      model based on continuous damage random threshold fuse network. The discrete
      lattice topology of the model is based on nacre's unique brick and mortar
      microarchitecture. The mechanical behavior of each of the bonds in the discrete
      lattice model is governed by the characteristic modular damage evolution of the
      organic matrix and the mineral bridges between the aragonite platelets. The
      numerical results obtained using this simple discrete lattice model are in very
      good agreement with the previously obtained experimental results, such as nacre's
      stiffness, tensile strength, and work of fracture. The analysis indicates that
      nacre's superior toughness is a direct consequence of ductility (maximum shear
      strain) of the organic matrix in terms of repeated unfolding of protein
      molecules, and its fracture strength is a result of its ordered brick and mortar
      architecture with significant overlap of the platelets, and shear strength of the
      organic matrix.

PMID- 15958245
TI  - Fruit and vegetable intake in African Americans income and store characteristics.
AB  - BACKGROUND: The purpose of this study was to examine whether the characteristics
      of retail food stores where African-American women shopped mediated the
      association between their income and intake of fruits and vegetables. Food store
      characteristics included store type (supermarket, specialty store, limited
      assortment store, independent grocer), store location (suburbs, city of Detroit),
      and perceptions of the selection/quality and affordability of fresh produce for
      sale. METHODS: The analysis drew upon data from a probability sample of 266
      African-American women living in 2001 in eastside Detroit, which had no
      supermarkets. Structural equation modeling was used to calculate a path model of
      direct and indirect effects. RESULTS: Women shopping at supermarkets and
      specialty stores consumed fruit and vegetables more often, on average, than those
      shopping at independent grocers. More positive perceptions of the
      selection/quality, but not affordability, of fresh produce at the retail outlet
      where they shopped was positively associated with intake, independent of store
      type and location as well as age, per capita income, and years of education. The
      results suggested an indirect association between income and fruit and vegetable
      intake; women with higher per capita incomes were more likely to shop at
      supermarkets than at other grocers, which in turn was associated with intake.
      CONCLUSIONS: Previous studies have shown that few supermarkets are located in the
      city of Detroit, a symptom of economic divestment over the past several decades.
      Results of this study suggest this may have negative implications for dietary
      quality, particularly among lower-income women.

PMID- 15958247
TI  - Cigarette tax increase and media campaign cost of reducing smoking-related
      deaths.
AB  - BACKGROUND: Tobacco use results in 500,000 premature deaths annually. Most
      smokers begin using tobacco before age 21, so the greatest impact on preventing
      smoking-related mortality is likely to come from campaigns targeting youths. This
      study estimates the cost-effectiveness of an anti-smoking media campaign and
      dollar 1 per pack increase in cigarette taxes on the lifetime decrease in smoking
      attributable mortality among the cohort of all 18-year-olds in the United States
      during the year 2000. METHODS: Cost-effectiveness analysis conducted from a
      societal perspective. RESULTS: The combined effects of a media campaign and
      dollar 1 per pack tax increase will result in a societal savings of between
      dollar 590,000 per life-year saved, at a 3% discount rate and dollar 1.4 million
      per life year saved, at a 7% discount rate. CONCLUSIONS: A media campaign and $1
      per pack cigarette tax increase will reduce overall smoking prevalence,
      significantly decrease smoking-attributable mortality, and decrease net societal
      costs.

PMID- 15958246
TI  - Self-management strategies mediate self-efficacy and physical activity.
AB  - BACKGROUND: Self-efficacy theory proposes that girls who have confidence in their
      capability to be physically active will perceive fewer barriers to physical
      activity or be less influenced by them, be more likely to pursue perceived
      benefits of being physically active, and be more likely to enjoy physical
      activity. Self-efficacy is theorized also to influence physical activity through
      self-management strategies (e.g., thoughts, goals, plans, and acts) that support
      physical activity, but this idea has not been empirically tested. METHODS:
      Confirmatory factor analysis was used to test the factorial validity of a measure
      of self-management strategies for physical activity. Next, the construct validity
      of the measure was tested by examining whether self-management strategies
      mediated the relationship between self-efficacy and self-reported physical
      activity, independently of several social-cognitive variables (i.e., perceived
      barriers, outcome expectancy value, and enjoyment), among cross-sectional samples
      of 6th grade (n=309) and 8th grade (n=296) girls tested between February 14 and
      March 17, 2002. Data were analyzed in 2004. RESULTS: Consistent with theory, self
      efficacy had direct effects on the social-cognitive variables. The primary novel
      finding is that self-management strategies mediated the association of self
      efficacy with physical activity in both samples. CONCLUSIONS: The measure of self
      management strategies for physical activity yields valid scores among adolescent
      girls and warrants experimental study as a mediator of the influence of efficacy
      beliefs on physical activity.

PMID- 15958248
TI  - Integrating hepatitis, STD, and HIV services into a drug rehabilitation program.
AB  - BACKGROUND: Considering the difficulties in providing screening and vaccination
      services for inmates in short-stay incarceration facilities, an evaluation was
      conducted of the integration of prevention services in an alternative sentencing
      drug rehabilitation program (alternative to incarceration) in San Diego CA.
      METHODS: During the period April 1999 to December 2002, clients were asked to
      complete a brief risk-assessment questionnaire, and were offered hepatitis B
      virus (HBV) vaccination, HBV and hepatitis C virus (HCV) serologic testing, STD
      screening, and HIV counseling and testing. RESULTS: Of the estimated 1125
      rehabilitation program enrollees, 930 (83%) participated in the integration
      program services. Most clients were male (64%), were aged >30 years (64%), and
      few (7%) reported previous HBV vaccination. Of the 854 clients eligible for
      hepatitis B vaccination, 98% received the first dose, 69% the second dose, and
      42% completed the series. Eleven percent of clients had prior HBV infection, and
      14.7% had HCV infection, with positivity rates being highest among those with a
      history of injection drug use-HBV, 19%, and HCV, 36%. HIV infection was rare
      (prevalence, 0.3%), and STDs were uncommon (chlamydia prevalence, 2%, and
      gonorrhea prevalence, 0.6%). Total annual cost of integration services (excluding
      HIV testing) was dollar 31,994 equating to dollar 122 per client served.
      CONCLUSIONS: Alternative sentencing drug rehabilitation programs provide a venue
      to efficiently deliver integrated hepatitis and other prevention services.
      Considering the vast number of high-risk persons in drug rehabilitation,
      probation, parole, and inmate release programs, an opportunity exists to greatly
      expand hepatitis services.

PMID- 15958249
TI  - Provider response to different formats of the adult immunization schedule.
AB  - BACKGROUND: Providers' failure to administer vaccines in accordance with
      established recommendations is a well-recognized barrier to national immunization
      efforts. This study evaluated the ease of use of two different formats of the
      Centers for Disease Control and Prevention's (CDC) adult immunization schedule by
      physicians in private practice, where the majority of adult immunizations are
      administered. METHODS: A series of focus groups was conducted with 94 physicians
      and other clinical staff in 11 private practices (family medicine and internal
      medicine) in six U.S. cities. Each session was based on a structured set of
      questions that explored barriers to adult immunizations, followed by three mock
      clinical scenarios to examine how each of two graphical depictions of the 2003
      2004 adult immunization schedule (one from the CDC's Advisory Committee on
      Immunization Practices, and the other from the Immunization Action Coalition)
      might facilitate assessments of recommended immunizations. Group dialogue and
      individual participants' written responses to the scenarios and the alternate
      schedule formats were analyzed. RESULTS: Providers perceived multiple barriers to
      adult immunization independent of immunization schedule formats, chiefly
      patients' low interest in immunization and refusal of vaccines. Most participants
      were not familiar with either format of CDC's adult immunization schedule before
      the study, but quickly developed strong preferences for one versus the other
      (usually the second format that they encountered). About half of the providers
      changed their vaccine recommendations for clinical scenarios when they consulted
      either schedule format, although some of the changes were not clinically
      appropriate. Participants suggested several ways to enhance the availability of
      the information contained in the schedule formats, especially through electronic
      means. CONCLUSIONS: This qualitative study suggests ways in which graphic
      depictions of an adult immunization schedule may address adult immunization
      barriers. Greater provider familiarity with schedule formats will be critical to
      their appropriate application in clinical encounters.

PMID- 15958250
TI  - Obesity and risk of nonfatal unintentional injuries.
AB  - BACKGROUND: Obesity is recognized as a risk factor for multiple chronic diseases.
      Yet, it is unclear whether obesity is also associated with an increased risk of
      nonfatal unintentional injury. METHODS: A population-based survey was conducted
      among adults aged > or = 18 years from January 1999 through October 2000. The
      relationship was investigated between body mass index (BMI), defined as weight in
      kilograms divided by the square of the height in meters (kg/m2), and risk of
      nonfatal unintentional injuries among 2575 respondents aged > or = 20 years by
      comparing percentage of adults between obese and nonobese respondents who had
      injuries. Multivariate logistic regression further examined this relationship by
      controlling for confounding demographics. RESULTS: A total of 370 respondents
      reported injuries in the previous year. We observed a linear dose-response trend
      among women. An estimated 7.0% of underweight individuals (BMI <18.5) reported
      injuries. In contrast, 26.0% of men and 21.7% of women with a BMI > or = 35.0
      reported injuries. The odds ratio of injuries for individuals with a BMI > or =
      35.0 was 2.00 (95% confidence interval=1.07-3.74, p<0.05) after controlling for
      gender, age, education level, marital status, family poverty status, and area of
      residence. CONCLUSIONS: A marginally significant association between extreme
      obesity and elevated risk of injuries was observed. Efforts to promote optimal
      body weight may reduce not only the risk of chronic diseases but also the risk of
      unintentional injury among overweight and obese individuals.

PMID- 15958251
TI  - Total and leisure-time walking among U.S. adults should every step count?
AB  - BACKGROUND: Although walking is a popular leisure-time activity, a substantial
      amount of total daily walking occurs in non-leisure contexts (i.e., occupation,
      transportation, and household work). Because non-leisure walking is not assessed
      by traditional leisure-time activity surveys, total walking among U.S. adults may
      be underestimated. This study describes walking estimates obtained from a measure
      of leisure-time activity and a specific measure of total walking in all contexts.
      METHODS: A national sample of adults (n=6626), selected by random-digit dialing,
      was surveyed between May 1999 and November 2000. Estimates of walking prevalence
      and of weekly time spent walking were examined from two separate modules: (1) an
      assessment restricted to leisure-time activity, and (2) an assessment of total
      walking. RESULTS: Walking prevalence based on the total walking module was nearly
      double that based on the leisure-time module (81% vs 43%, respectively). The
      median weekly minutes of walking also nearly doubled using the total walking
      module (239 vs 130 minutes, respectively). Among those with jobs involving
      substantial walking, median weekly walking minutes were more than three times
      greater with the total walking module (476 vs 130 minutes, respectively).
      CONCLUSIONS: U.S. adults, particularly those with jobs involving walking, do a
      substantial amount of walking not captured by traditional leisure-time activity
      surveys. This may affect the appropriate targeting of physical activity
      interventions, as well as the evaluation of the effectiveness of physical
      activity promotions and policies. However, further characterization of non
      leisure walking is needed to determine its contribution to health and meeting
      physical activity guidelines.

PMID- 15958252
TI  - Do mass media affect Medicare beneficiaries' use of diabetes services?
AB  - BACKGROUND: Appropriate secondary preventive care for people with diabetes can
      reduce complications and premature death, yet many people with diabetes do not
      get these services. Mass media may influence individual health behavior. METHODS:
      In 1999, the West Virginia Medical Institute (WVMI) began a long-term radio and
      television campaign to educate West Virginia Medicare beneficiaries with diabetes
      about the importance of foot exams, eye exams, HbA1c testing, and influenza and
      pneumonia immunizations using messages with an "Ask your doctor about..."
      formula. To assess campaign efficacy, WVMI commissioned a telephone survey of
      1500 randomly selected beneficiaries likely to have diabetes in two groups of
      counties with differing exposure to the messages. The survey asked whether the
      beneficiary had heard the messages and responded to them, by message topic.
      RESULTS: Nearly everyone (90%) in both survey groups said they had seen or heard
      the diabetes ads. However, high-exposure group members were about 1.2 times more
      likely to recall hearing most messages than low-exposure group members, and were
      1.2 to 1.8 times more likely to say that they did what the messages suggested.
      CONCLUSIONS: Media campaigns with preventive health messages targeted to Medicare
      beneficiaries with diabetes can reach them and may induce appropriate responses.

PMID- 15958253
TI  - Market for colorectal cancer screening by endoscopy in the United States.
AB  - In the United States, colorectal cancer (CRC) ranks third among all cancer sites
      in incidence, and second in cancer-related mortality. Although screening reduces
      CRC incidence and mortality, current screening rates among the average-risk
      population are low. The traditional way of promoting CRC screening has been to
      educate healthcare providers and the public on its benefits, available screening
      procedures, and current guidelines. In this paper, we focus on economics and
      provide an overview of some key factors that affect the demand for and the supply
      of CRC screening by endoscopy. Factors affecting the demand for endoscopic CRC
      screening include the number of people for whom screening is recommended,
      consumers' income and health insurance status, time and travel costs, prices of
      non-endoscopic CRC screening tests, and personal preferences and perceived
      quality of care. Factors influencing the supply of endoscopic screening include
      the availability of endoscopic providers, increased efficiency, procedure costs,
      current reimbursement rates for endoscopic procedures, and technical progress.
      The volume of screening tests in the market is determined jointly by the
      collective demand and supply decisions of consumers and providers. The discussion
      includes policy implications for the current effort to promote widespread use of
      CRC screening in the United States.

PMID- 15958254
TI  - Worksite health promotion programs with environmental changes: a systematic
      review.
AB  - BACKGROUND: It is now widely believed that health promotion strategies should go
      beyond education or communication to achieve significant behavioral changes among
      the target population. Environmental modifications are thought to be an important
      addition to a worksite health promotion program (WHPP). This review aimed to
      systematically assess the effectiveness of WHPPs with environmental
      modifications, on physical activity, dietary intake, and health risk indicators.
      METHODS: Online searches were performed for articles published up to January 2004
      using the following inclusion criteria: (1) (randomized) controlled trial
      (RCT/CT); (2) intervention should include environmental modifications; (3) main
      outcome must include physical activity, dietary intake, and health risk
      indicators; and (4) healthy working population. Methodologic quality was assessed
      using a checklist derived from the methodologic guidelines for systematic reviews
      (Cochrane Back Review Group), and conclusions on the effectiveness were based on
      a rating system of five levels of evidence. RESULTS: Thirteen relevant, mostly
      multicenter, trials were included. All studies aimed to stimulate healthy dietary
      intake, and three trials focused on physical activity. Follow-up measurements of
      most studies took place after an average 1-year period. Methodologic quality of
      most included trials was rated as poor. However, strong evidence was found for an
      effect on dietary intake, inconclusive evidence for an effect on physical
      activity, and no evidence for an effect on health risk indicators. CONCLUSIONS:
      It is difficult to draw general conclusions based on the small number of studies
      included in this review. However, evidence exists that WHPPs that include
      environmental modifications can influence dietary intake. More controlled studies
      of high methodologic quality need to be initiated that investigate the effects of
      environmental interventions on dietary intake and especially on physical activity
      in an occupational setting.

PMID- 15958255
TI  - Financing vaccines in the 21st century: recommendations from the National Vaccine
      Advisory Committee.
AB  - In 2003, the National Vaccine Advisory Committee (NVAC) formed a working group to
      examine recommendations related to vaccine financing contained in the 2003
      Institute of Medicine report on financing immunizations, "Financing Vaccines in
      the 21st Century: Assuring Access and Availability." During 2003-2004, the
      working group conducted a series of activities leading to a meeting with
      stakeholders in June 2004. Based on these discussions and meetings, NVAC
      recommended that the Department of Health and Human Services (DHHS) not adopt the
      Institute of Medicine (IOM) recommendation to replace the current immunization
      financing system with an insurance mandate and system of subsidies and vouchers.
      NVAC instead proposed substantial, but incremental, changes to the current system
      that would go a long way toward stabilizing the financing of immunizations in the
      United States. The proposed changes include expanded and stable funding for the
      existing immunization grant program, expansion of the Vaccines for Children
      program, regulatory harmonization, promotion of "first dollar" insurance coverage
      for immunizations, and the assurance of adequate reimbursement for the
      administration of vaccines.

PMID- 15958256
TI  - Scoping out the screening market.

PMID- 15958257
TI  - IS6110 DNA fingerprinting analysis of individually separated colonies of
      Mycobacterium tuberculosis.
AB  - There are no data so far that show IS6110 restriction fragment length
      polymorphism (RFLP) patterns of individually separated tuberculosis bacilli from
      clinical isolates, and their alterations during follow-up surveys. We picked 20
      60 tuberculosis clones from clinical isolates under anti-tuberculosis medication,
      and individually analysed their DNA fingerprinting patterns using IS6110 RFLP as
      well as spoligotyping as a second typing. The study using cloned bacilli of
      Mycobacterium tuberculosis showed that clinical isolates contained several clones
      with different DNA fingerprints and that their band patterns altered weakly but
      distinctly during follow-up surveys. However, there was no significant difference
      in the fingerprinting patterns when clinical isolates were to RFLP without
      separating to subjected/individual colonies. In view of the IS6110 RFLP of
      individually separated tuberculosis bacilli, we have now speculated several
      possibilities: (1) that clones with different DNA fingerprints exist in clinical
      isolates; (2) that IS6110 RFLP patterns of the materials depend on the population
      of the original clone and the variants having DNA fingerprints different from the
      original pattern; and (3) that their band patterns are influenced not only by the
      stability of the original germ having its own fingerprint, but also by the
      fragility of the new clones.

PMID- 15958258
TI  - Expression, immunochemical characterization and localization of the Mycobacterium
      tuberculosis protein p27.
AB  - Rv2108 is a gene of the PPE family of Mycobacterium tuberculosis specific for
      this bacterial complex and that may encode a putative protein p27. This gene was
      amplified, inserted into bacterial vectors, sequenced, and expressed as a
      recombinant protein. Specific antibodies to this protein were generated and used
      for immunochemical characterization and cellular localization. Mass spectrometric
      analysis of the expressed protein revealed a molecule that corresponded to the
      p27 putative protein. The expressed protein was immunologically active, and
      reacted with antibodies from tuberculosis patient sera. Specific immunoblot
      analysis confirmed the presence of the p27 antigen in Mycobacterium bovis BCG
      strain and in human clinical isolates of M. tuberculosis, but not in other
      mycobacteria tested. Western blot and immunoelectron microscopic analysis of BCG
      strain indicated that the p27 protein is localized in the membrane of the cell.
      The specific expression of the p27 protein in the M. tuberculosis complex could
      provide a novel specific complimentary diagnostic test for the presence of and
      infection with M. tuberculosis.

PMID- 15958259
TI  - Susceptibility of brushtail possums (Trichosurus vulpecula) infected with
      Mycobacterium bovis is associated with a transient macrophage activation profile.
AB  - The Australian brushtail possums are highly susceptible to Mycobacterium bovis
      and are the principal wildlife reservoir of M. bovis in New Zealand. To better
      understand the disease process in these animals, brushtail possums were infected
      by the aerosol route with a virulent strain of M. bovis, and immune parameters
      measured. M. bovis replicated actively in the lungs of infected animals. Animals
      began developing macroscopic lung lesions at 4 and 5 weeks following infection,
      with some lesions appearing in the livers and spleens. Infection determined the
      emergence of blood lymphocytes which proliferated in response to bovine purified
      protein derivative from M. bovis (PPD-b) at 3, 4 and 5 weeks. The response to a
      mitogen (Concanavalin A) waned progressively with time. Infection was associated
      with a modest increase in the numbers of free lung cells. Nitrite was detectable
      in the lavage fluids of infected animals at 3 weeks postinfection, but not at 4
      and 5 weeks. Macrophage activation in the lungs was evident as alveolar
      macrophages produced more oxidants, significant levels of nitric oxide (NO), as
      well as tumor necrosis factor alpha (TNF-alpha) bioactivity at 3 weeks
      postinfection. However, macrophages from infected animals lost the ability to
      generate nitrite- and TNF-alpha generation was depressed at 4 and 5 weeks
      postinfection, the time at which macroscopic lesions in the lungs became
      apparent. Alveolar macrophages from animals at 3 weeks postinfection blocked the
      replication of M. bovis in part via a NO-dependent mechanism, and were more
      refractory for M. bovis growth than cells from naive animals to bacterial
      replication. Alveolar macrophages from animals at 4 and 5 weeks postinfection
      allowed substantial replication of M. bovis, and no NO-dependent bacteriostatic
      activity was apparent. Introduction of autologous lymphocytes from the blood of
      infected animals in co-cultures rendered infected macrophages more resistant to
      M. bovis replication. We conclude that M. bovis infection in brushtail possums is
      associated with a transient activation of alveolar macrophages, although in vitro
      exposure to sensitized T cells can enhance this profile.

PMID- 15958260
TI  - Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary
      tuberculosis in the guinea pig.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is suggested to play multiple roles in
      immune and pathologic responses in tuberculosis. In this study, we have developed
      a system for the expression of recombinant guinea pig TNF-alpha (rgpTNF-alpha).
      Using rgpTNF-alpha along with neutralizing anti-rgpTNF-alpha antiserum, we tested
      the effect of modulating the levels of TNF-alpha on antigen-specific T cell
      proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of PPD
      pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation.
      Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of
      PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG
      vaccinated guinea pigs were treated with polyclonal rgpTNF-alpha antiserum
      throughout the first 3 weeks following low-dose, pulmonary infection with
      Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated
      guinea pigs. We also detected higher levels of splenic granuloma organization in
      the non-vaccinated group as well as a significant number of plasma cells
      associated with granulomata from the BCG-vaccinated group. These results suggest
      that modulating the availability of TNF-alpha in BCG-vaccinated guinea pigs can
      lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of
      humoral immunity. Conversely, abrogating TNF-alpha activity in the context of a
      hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue
      them from immunopathological consequences of overproducing TNF-alpha.

PMID- 15958261
TI  - Frequency of DRB1-DQB1 two-locus haplotypes in tuberculosis: preliminary report.
AB  - Analysis of correlation between tuberculosis (TB) and human leukocyte antigen
      (HLA) in populations from Asia and Latin America has shown conflicting results.
      The aim of this study was to evaluate the frequency of HLA-DRB1-DQB1 two-locus
      haplotypes of 61 TB patients and 125 healthy volunteers in the same ethnic group
      in Poland. DRB1 and DQB1 alleles were determined by PCR-SSP "low-resolution" and
      "high-resolution" methods. Our study showed that DRB1*1601 and DQB1*0502 alleles
      were more frequent, whereas DQB1*0201 was rarer in TB than in controls. DRB1*16
      DQB1*05, DRB1*04-DQB1*03 and DRB1*1601-DQB1*0502 haplotype were more common, and
      DRB1*11-DQB1*03 less frequent in TB in comparison to controls. Positive linkage
      disequilibrium (LD) for DRB1*01-DQB1*05, DRB1*03-DQB1*02, DRB1*11-DQB1*03,
      DRB1*13-DQB1*06 and DRB1*15-DQB1*06 was found in controls. A trend towards the
      positive LD for DRB1*01-DQB1*05, DRB1*03-DQB1*02, DRB1*11-DQB1*03, DRB1*15
      DQB1*06 and DRB1*16-DQB1*05 was shown in TB. The trend towards the positive LD
      for DRB1*16-DQB1*05 haplotype in TB patients was not observed in the control
      group. It seems likely that the presence of DRB1*1601, DQB1*0502 alleles and
      DRB1*1601-DQB1*0502, DRB1*04-DQB1*03, DRB1*14-DQB1*05 haplotypes may be related
      to a higher risk of developing TB, whereas low frequency of DQB1*0201 and DRB1*11
      DQB1*03 haplotype may be linked to the resistance to TB.

PMID- 15958262
TI  - HERG mutation predicts short QT based on channel kinetics but causes long QT by
      heterotetrameric trafficking deficiency.
AB  - OBJECTIVE: Mutations in the KCNH2 (hERG, human ether-a-go-go related gene) gene
      may cause a reduction of the delayed rectifier current I(Kr), thereby leading to
      the long QT syndrome (LQTS). The reduced I(Kr) delays the repolarisation of
      cardiac cells and renders patients vulnerable to ventricular arrhythmias and
      sudden death. We identified a novel mutation in a LQTS family and investigated
      its functional consequences using molecular and microscopic techniques. METHODS
      AND RESULTS: Genetic screening in the LQTS family revealed a heterozygous
      frameshift mutation p.Pro872fs located in the C-terminus of the KCNH2 gene. The
      mutation leads to a premature truncation of the C-terminus of the hERG protein.
      p.Pro872fs channels lack 282 amino acids at the C-terminus and possess an extra 4
      amino acid tail. Both the kinetic and biochemical properties of the p.Pro872fs
      and p.Pro872fs/WT channels were studied in HEK293 cells and resulted in a novel
      proof of concept for heterozygous LQTS mutations: homotetrameric p.Pro872fs
      channels displayed near-normal expression, trafficking, and channel kinetics.
      Unexpectedly, upon co-expression of p.Pro872fs and WT channels, the repolarising
      power (the proportion of hERG current contributing to the action potential as the
      percentage of the total current available) was substantially higher during action
      potential clamp experiments as compared to WT channels alone. This would lead to
      a shorter rather than a prolonged QT interval. However, at the same time,
      heterotetramerisation of p.Pro872fs and WT channels also caused a dominant
      negative effect on trafficking by an increase in ER retention of these
      heterotetrameric channels, which surpassed the former gain in repolarising power.
      CONCLUSION: The LQTS phenotype in the studied family is caused by a mutation with
      novel properties. We demonstrate that a KCNH2 mutation that clinically leads to
      long QT syndrome causes at the cellular level both a "gain" and a "loss" of HERG
      channel function due to a kinetic increase in repolarising power and a decrease
      in trafficking efficiency of heteromultimeric channels.

PMID- 15958264
TI  - Influence of aminoglutethimide and spironolactone on the efficacy of
      carbamazepine and diphenylhydantoin against amygdala-kindled seizures in rats.
AB  - Antagonists of steroid receptors may interfere with seizure phenomena. The
      present study deals with effects of aminoglutethimide and spironolactone on the
      action of carbamazepine and diphenylhydantoin in amygdala-kindled rats of both
      genders. Co-administration of the antimineralocorticoid with carbamazepine at
      their ineffective doses (50 and 15 mg/kg, respectively) led to significant
      reduction of the seizure and afterdischarge durations. No anticonvulsant effect
      was observed when spironolactone was combined with diphenylhydantoin. The
      concomitant treatment of aminoglutethimide and carbamazepine (both drugs at their
      subprotective doses of 5 and 15 mg/kg, respectively) resulted in antiseizure
      activity in respect of all measured parameters, including the afterdischarge
      threshold, seizure severity, seizure duration and afterdischarge duration. The
      similar combination of aminoglutethimide with diphenylhydantoin (2.5 mg/kg)
      significantly shortened the seizure and afterdischarge durations. The antiseizure
      effect of tested combinations was not sex-dependent and not reversed by
      hydrocortisone pretreatment. Pharmacokinetic events may be involved only in the
      interaction between spironolactone and carbamazepine. Among various
      chemoconvulsants, bicuculline reversed the action of aminoglutethimide on
      carbamazepine and diphenylhydantoin. The effect of aminoglutethimide on
      diphenylhydantoin was also abolished by N-methyl-d-aspartic acid and
      aminophylline. In conclusion, our results suggest that doses of carbamazepine and
      diphenylhydantoin should be modified in epileptic patients concomitantly treated
      with aminoglutethimide or spironolactone.

PMID- 15958263
TI  - The diacylglycerol lipase inhibitor RHC-80267 potentiates the relaxation to
      acetylcholine in rat mesenteric artery by anti-cholinesterase action.
AB  - The diacylglycerol lipase inhibitor 1,6-bis(cyclohexyloximinocarbonylamino)
      hexane (RHC-80267) was tested for its effect on acetylcholine-evoked relaxation
      in rat mesenteric artery. In artery contracted with either noradrenaline or KCl,
      RHC-80267 (0.1-10 muM) potentiated the relaxation evoked by acetylcholine. The
      effect of RHC-80267 was not affected by nitric oxide synthase inhibition or by
      inhibitors of protein kinase C or of phospholipase A(2). The diacylglycerol
      analogue 1-oleoyl-2-acetyl-sn-glycerol did not change the relaxation to
      acetylcholine. RHC-80267 did not affect the relaxation evoked by carbachol, by
      the nitric oxide donor SNAP (S-nitroso-N-acetylpenicillamine) or by the K(+)
      channel opener cromakalim. Neostigmine, a cholinesterase inhibitor, produced the
      same effect as RHC-80267 on acetylcholine-evoked relaxation. When tested on
      cholinesterase in brain homogenate, RHC-80267 concentration-dependently inhibited
      cholinesterase activity with an IC(50) of 4 muM. These results indicate that the
      potentiation of acetylcholine-evoked responses by RHC-80267 in rat mesenteric
      artery is caused by the inhibition of the cholinesterase activity in the vascular
      wall.

PMID- 15958265
TI  - Nucleated red blood cells in infants of women with preterm labor and pre
      eclampsia.

PMID- 15958266
TI  - Cognitive impairment in spinocerebellar ataxia type 8.
AB  - OBJECTIVES: Only a limited number of studies have investigated the cognitive
      performances of spinocerebellar ataxia (SCA) patients. In none of the SCA8
      studies have the neuropsychological test performances been the primary measures.
      The objective of the current study was to investigate the characteristics of
      cognitive deficits in SCA8. METHODS: Ten SCA8 patients and ten case-by-case
      matched control subjects underwent a comprehensive neuropsychological examination
      evaluating attention and information processing, concept formation, reasoning and
      executive functions, verbal production, memory and learning and visuoperceptual
      and -constructive functions. RESULTS: SCA8 patients demonstrated deficits
      primarily in attention and information processing, as well as in concept
      formation, reasoning, executive functions and verbal production. Visuoperceptual
      and -constructive functions, as well as most of the performances of memory were
      unaffected. CONCLUSIONS: Cognitive impairments, especially those related to
      attention, information processing and executive functions, seem to be a clinical
      feature of SCA8 disease.

PMID- 15958267
TI  - Focal neurological injury caused by West Nile virus infection may occur
      independent of patient age and premorbid health.
AB  - INTRODUCTION: Limited evidence suggests that focal neurological injury (e.g.,
      acute flaccid paralysis) caused by infection with the West Nile virus (WNV) is
      more common in older patients. We re-evaluate this association in a series of
      patients who were infected with the WNV during the 2002 epidemic. METHODS: We
      performed a retrospective chart review of 34 patients who were hospitalized for
      treatment of serologically confirmed WNV infection. Measurements included the
      patient's demographic characteristics, baseline medical diagnoses, the occurrence
      of symptoms and exam findings, the results of various diagnostic tests, and the
      patient's clinical outcome. RESULTS: Patients infected with the WNV who developed
      focal neurological injury were found to be comparable to patients who did not
      develop focal neurological injury both in terms of patient age and the number of
      medical conditions the patient had prior to infection. This is in contrast to WNV
      infected patients who developed an encephalitis-like clinical course, or who died
      or were institutionalized after their hospitalization; such patients tended to be
      older and-in cases with a poor outcome-have more medical conditions prior to WNV
      infection. CONCLUSIONS: In our patient group, focal neurological injury caused by
      WNV infection was not related to advanced patient age or to the number of medical
      conditions the patient had prior to infection. Our findings bring into question
      commonly held views about the development of focal neurological injury caused by
      WNV infection, and they raise concerns about the management of future WNV
      epidemics and the testing and use of potential antiviral treatments against this
      infection.

PMID- 15958268
TI  - Sex differences in behavioral effects of cannabinoids.
AB  - This review summarizes the existing literature on sex differences in the effects
      of cannabinoid drugs on behavior, primarily in the adult rodent. These
      preclinical studies, taken together with preliminary reports of sex differences
      in cannabinoid effects in humans, suggest that sex of subject may be an important
      modulating factor in a variety of cannabinoid effects. When sex differences are
      found, females are usually more sensitive than males to cannabinoids. Both
      pharmacokinetic and pharmacodynamic variables may contribute to sex differences
      in behavioral effects of cannabinoids. Given the significant therapeutic
      potential of cannabinoid agonists and antagonists--as well as their widespread
      recreational use--it will be important to determine the reliability and
      functional significance of, as well as mechanisms underlying sex differences in
      cannabinoid effects.

PMID- 15958269
TI  - L-carnitine and propionyl-L-carnitine improve endothelial dysfunction in
      spontaneously hypertensive rats: different participation of NO and COX-products.
AB  - L-carnitine and propionyl-L-carnitine are supplements to therapy in
      cardiovascular pathologies. Their effect on endothelial dysfunction in
      hypertension was studied after treatment with either 200 mg/kg of L-carnitine or
      propionyl-L-carnitine during 8 weeks of spontaneously hypertensive rats (SHR) and
      normotensive Wistar Kyoto rats (WKY). Endothelial function was assessed in aortic
      rings by carbachol-induced relaxation (CCh 10(-8) to 10(-4) M) and factors
      involved were characterized in the presence of the inhibitors: L-NAME,
      indomethacin, the TXA2/PGH2 Tp receptor antagonist ICI-192,605 and the
      thromboxane synthetase inhibitor-Tp receptor antagonist, Ro-68,070. The effect on
      phenylephrine-induced contractions was also observed. To identify the nature of
      vasoactive COX-derived products, enzyme-immunoassay of incubation media was
      assessed. Involvement of reactive oxygen species was evaluated by incubating with
      superoxide dismutase and catalase. Nitric oxide production was evaluated by serum
      concentration of NO2+NO3.Treatment with both compounds improved endothelial
      function of rings from SHR without blood pressure change. Propionyl-L-carnitine
      increased NO participation in WKY and SHR. L-carnitine reduced endothelium
      dependent responses to CCh in WKY due to an increase of TXA2 production. In both
      SHR and WKY, L-carnitine enhanced concentration of PGI2 and increased
      participation of NO. Results in the presence of SOD plus catalase show that it
      might be related to antioxidant properties of L-carnitine and propionyl-L
      carnitine. Comparison between the effect of both compounds shows that both may
      reduce reactive oxygen species and increase NO participation in endothelium
      dependent relaxations in SHR. However, only L-carnitine was able to increase the
      release of the vasodilator PGI2 and even enhanced TXA2 production in normotensive
      rats.

PMID- 15958270
TI  - Insulin resistance does not impair contractile responses of cerebral arteries.
AB  - Insulin resistance (IR) impairs endothelium-mediated vasodilation in cerebral
      arteries as well as K+ channel function in vascular smooth muscle. Peripheral
      arteries also show an impaired endothelium-dependent vasodilation in IR and
      concomitantly show an enhanced contractile response to endothelin-1 (ET-1).
      However, the contractile responses of the cerebral arteries in IR have not been
      examined systematically. This study examined the contractile responses of
      pressurized isolated middle cerebral arteries (MCAs) in fructose-fed IR and
      control rats. IR MCAs showed no difference in pressure-mediated (80 mmHg)
      vasoconstriction compared to controls, either in time to develop spontaneous tone
      (control: 61+/-3 min, n=30; IR: 63+/-2 min, n=26) or in the degree of that tone
      (control: 60 min: 33+/-2%, n=22 vs. IR 60 min: 34+/-3%, n=17). MCAs treated with
      ET-1 (10(-8.5) M) constrict similarly in control (53+/-3%, n=14) and IR (53+/-3%,
      n=14) arteries. Constrictor responses to U46619 (10(-6) M) are also similar in
      control (48+/-9%, n=8) and IR (42+/-5%, n=6) MCAs as are responses to
      extraluminal uridine 5'-triphosphate (UTP; 10(-4.5) M) (control: 35+/-7%, n=11
      vs. IR: 38+/-3%, n=10). These findings demonstrate that constrictor responses
      remain intact in IR despite a selective impairment of dilator responses and
      endothelial and vascular smooth muscle K+ channel function in cerebral arteries.
      Thus, it appears that the increased susceptibility to cerebrovascular
      abnormalities associated with IR and diabetes (including cerebral ischemia,
      stroke, vertebrobasilar transient ischemic attacks) is not due to an enhanced
      vasoreactivity to constrictor agents.

PMID- 15958271
TI  - Effects of cyclohexenonic long-chain fatty alcohol on diabetic rat trachea.
AB  - In order to investigate the diabetes-associated neuropathy and prevent effects of
      cyclohexenonic long-chain fatty alcohol, a neurotrophic substance, in trachea, we
      studied its effect on streptozotocin-diabetic hyper-reactivity in the rat
      trachea. Diabetes was induced in 8-week-old male Sprague-Dawley rats by
      administering an intraperitoneal injection of streptozotocin (50 mg/kg). The rats
      were divided randomly into four groups and were maintained for four weeks: age
      matched control rats, diabetic rats without treatment with cyclohexenonic long
      chain fatty alcohol, and diabetic rats treated with cyclohexenonic long-chain
      fatty alcohol (2 and 8 mg/kg, i.p. every day). The serum glucose and insulin
      levels were determined, and the contractile responses of the trachea induced by
      carbachol and KCl were investigated. Treatment with cyclohexenonic long-chain
      fatty alcohol did not alter the rats' diabetic status, i.e., body weight,
      thickness of the trachea, serum glucose levels, and serum insulin levels, but
      significantly improved the diabetic-induced hyper-reactivity of the rat trachea
      in a dose-dependent manner. There was no significant difference in either the
      carbachol- or KCl-induced contractile forces between groups with or without
      mucosa in the functional studies. In histological examinations, thinning of
      cricoid cartilage, thickness of basal membrane, and degeneration, fragmentation
      of elastic fibers in the submucosal layer, and hypertrophy of smooth muscle
      bundle in the membranous wall of trachea were observed in the diabetic rat
      trachea, which were improved by treatment with cyclohexenonic long-chain fatty
      alcohol. Our data indicate that this drug can prevent hyper-reactivity in the
      diabetic trachea.

PMID- 15958272
TI  - Role of cytochrome P-450 in schisandrin B-induced antioxidant and heat shock
      responses in mouse liver.
AB  - In order to explore the role of cytochrome P-450 (P-450) in schisandrin B (Sch B)
      induced antioxidant and heat shock responses, the effect of 1-aminobenzotriazole
      (ABT, a broad spectrum inhibitor of P-450) on hepatic mitochondrial glutathione
      antioxidant status (mtGAS) and heat shock protein (Hsp)25/70 expression was
      examined in Sch B-treated mice. The non-specific and partial inhibition of
      cytochrome P-450 (P-450) by ABT pretreatment significantly caused a protraction
      in the time-course of Sch B-induced enhancement in hepatic mitGAS and Hsp25/70
      expression in mice. Using mouse liver microsomes as a source of P-450, Sch B, but
      not dimethyl diphenyl bicarboxylate (a non-hepatoprotective analog of Sch B), was
      found to serve as a co-substrate for the P-450-catalyzed NADPH oxidation
      reaction, with a concomitant production of oxidant species. Taken together, the
      results suggest that oxidant species generated from P-450-catalyzed reaction with
      Sch B may trigger the antioxidant and heat shock responses in mouse liver.

PMID- 15958273
TI  - Anti-oxidative and anti-inflammatory activities of two different species of a
      Chinese herb I-Tiao-Gung.
AB  - The anti-oxidative and anti-inflammatory activities of two different species of
      traditional Chinese medicines that shared the same name have been studied. The
      extracts of Glycine radix have higher activities in free radical-scavenging
      activity determined with DPPH, reduction in hemoglobin-catalyzed lipid auto
      oxidation and inhibition of the lipoxygenase (LOX) and cyclooxygenase (COX)
      catalyzed arachidonate oxidation compared to the activities of extract of
      Flemingia. One of the significant bioactive constituents of Glycine radix has
      been isolated and identified as daidzein.

PMID- 15958274
TI  - Cannabinoids and ceramide: two lipids acting hand-by-hand.
AB  - Cannabinoids, the active components of Cannabis sativa (marijuana) and their
      endogenous counterparts, exert their effects by binding to specific G-protein
      coupled receptors that modulate adenylyl cyclase and ion channels. Recent
      research has shown that the CB1 cannabinoid receptor is also coupled to the
      generation of the lipid second messenger ceramide via two different pathways:
      sphingomyelin hydrolysis and ceramide synthesis de novo. Sustained ceramide
      accumulation in tumor cells mediates cannabinoid-induced apoptosis, as evidenced
      by in vitro and in vivo studies. This effect seems to be due to the impact of
      ceramide on key cell signalling systems such as the extracellular signal
      regulated kinase cascade and the Akt pathway. These findings provide a new
      conceptual view on how cannabinoids act, and raise interesting physiological and
      therapeutic questions.

PMID- 15958275
TI  - Protective effect of melatonin against oxidative stress on adhesion formation in
      the rat cecum and uterine horn model.
AB  - This experimental study was designed to evaluate the degree of adhesion formation
      and peritoneal tissue levels of malondialdehyde (MDA), reduced glutathione (GSH)
      and nitric oxide (NO) and the effect of melatonin on these metabolites in a
      postoperative intraperitoneal adhesion formation model in rats. Thirty adult
      female Wistar albino rats were subjected to standardized lesions by cecal and
      uterine horn abrasion and were randomly divided into three groups. Control rats
      were treated with 5% ethanol. Melatonin treated rats received 4 mg/kg melatonin
      before closure and for 10 consecutive days intraperitoneally after surgery. Rats
      in the sham operation group underwent a surgical procedure similar to the other
      groups however the peritoneal abrasion was not performed. On postoperative day 10
      relaparatomy was performed. After the assessment of the adhesions, the rats in
      each group were sacrificed and peritoneal tissues were harvested to determine the
      tissue levels of MDA, GSH and NO activity. Adhesion formation scores in the
      melatonin group were significantly lower than that of control and sham group
      (p<0.01 and p<0.02, respectively). Tissue levels of MDA and NO were significantly
      lower in the melatonin treated rats when compared with control and sham groups.
      The levels of GSH in the melatonin treated rats were significantly higher than
      those of control and sham groups (p<0.01). The results demonstrate that in this
      experimental model, intraperitoneal administration of melatonin decreases the
      extent of peritoneal adhesions and causes a decrease in MDA and NO and an
      increase in GSH levels.

PMID- 15958276
TI  - Effective combination of minocycline and interferon-beta in a model of multiple
      sclerosis.
AB  - The objective of the current study was to investigate whether minocycline
      improves the effect of an existing multiple sclerosis (MS) medication, interferon
      beta, on experimental autoimmune encephalomyelitis (EAE) in mice. When used at
      sub-optimal doses, neither medication affected EAE but their combination at these
      doses led to the significant alleviation of EAE disease severity scores and
      histological outcomes. In culture, the toxicity of T cells to neurons was
      alleviated by their prior exposure to minocycline or interferon-beta and their
      combination further attenuated neuronal death. Collectively, these results
      suggest the utility of the combination of minocycline and interferon-beta in MS.

PMID- 15958278
TI  - Why does neuroblastoma attract us so much?

PMID- 15958277
TI  - Phosphorylation of the gap junction protein Connexin43 in CIN III lesions and
      cervical carcinomas.
AB  - Connexins are proteins that form the connexons, gap junction structures, which
      allow cells to communicate. Phosphorylation of connexins has been found to impair
      this communication. Using an antibody specifically recognizing the S279/S282
      phosphorylated form of connexin43 (Cx43) for immunohistochemistry, we have
      analysed Cx43 phosphorylation in normal epithelium, CIN III lesions, and
      carcinomas of the cervix. We found that in normal epithelium the basal layer was
      devoid of staining and most of the protein was localized in stratum spinosum and
      stratum granulosum. In pre-malignant CIN-III lesions Cx43 was strongly
      phosphorylated, but the basal layer was still negative. In squamous carcinomas,
      the cells were intensely stained. In these tumours, sites of strong staining were
      adjacent to less stained regions, suggesting that the tumours are intrinsically
      heterogeneous. Immunoblotting of proteins extracted from carcinomas with the
      specific antibody showed the classical pattern of multiple reacting bands, with
      the appearance of low migrating forms of the protein. Our results suggest that
      increased S279/S282 phosphorylation of Cx43 is the result of altered tissue
      structure rather than of cell malignization.

PMID- 15958279
TI  - Detection of caspase-3 activation in single cells by fluorescence resonance
      energy transfer during photodynamic therapy induced apoptosis.
AB  - In many apoptosis pathways, activation of caspase-3 is considered the final
      stage. In this study, we studied PDT induced caspase-3 activation with
      fluorescence resonance energy transfer (FRET) technique. A recombinant caspase-3
      substrate, SCAT3, was used as the FRET probe. FRET fluorescence images were
      collected after PDT or TNF-alpha induced apoptosis. By analyzing the dynamic
      changes of FRET fluorescence, the results indicate that the caspase-3 activation
      started immediately after the PDT treatment. In contrast, FRET disruption caused
      by caspase-3 activation started at 3h after TNF-alpha treatment, due to different
      signaling pathway. The results have proofed, for the first time, that FRET is a
      sensitive technique that can be used to investigate PDT-induced activation of
      caspase-3 in real-time and in single cells. By choosing appropriate recombinant
      substrates as FRET probes, it is likely that FRET technique will provide a new
      real-time means to study the mechanism of PDT at single cell level.

PMID- 15958280
TI  - Psychobiological perspectives on somatoform disorders.
AB  - Common physical symptoms such as abdominal pain, headache, back pain and
      dizziness play a major role for the health care system. Existing models for the
      development and maintenance of these symptoms emphasize a vicious circle with
      cognitive-perceptual, behavioral, and psychobiological components. In this
      manuscript, we present examples of psychobiological factors that might contribute
      to somatoform disorders. We emphasize that somatoform symptoms are not strictly
      mental events, but are associated with a diversity of biological processes. The
      possible role of the endocrine and immune system, amino acids and
      neurotransmitters, but also physiological activation and cerebral activity is
      exemplified. These approaches are categorized using a model of perception and
      filtering of bodily signals. Studies are needed that combine the investigation of
      different biological systems with assessments of psychological variables in
      longitudinal trials, but also experimental investigations in humans examining the
      interaction of behavior changes, biological variations, and body perception are
      still rare.

PMID- 15958281
TI  - Developmental determinants of sensitivity and resistance to stress.
AB  - The purpose of this paper is two fold. First, to revisit the issue of the
      definition of stress and to highlight the difficulties with the contemporary
      definitions and, second, to review the literature on the influence of early
      experiences on the endocrine stress responses and behavior in rodents, sub-human
      primates and humans. Early experiences, usually involving some manipulation that
      results in disruption of the mother-infant relationship, have been shown to have
      long-term influences on the behavioral and endocrine responses to stress. In the
      rodent, brief periods of separation result in an attenuated adrenal response to
      stress (reduced secretion of corticosterone). In contrast, longer periods of
      separation result in an exaggerated response and several behavioral anomalies
      i.e. increased alcohol consumption, increased startle response etc. However, the
      effects of disruptions of the mother-infant relationships in primates reveal a
      pattern of behavioral disturbance but little influence on the endocrine response.
      Brief maternal separations result in a blunted cortisol response in juvenile
      squirrel monkeys. The long-term effects of early experiences in humans are very
      difficult to interpret. It is not possible to determine the length and severity
      of the experiences, and when in development the experiences were imposed on the
      child. Despite these limitations, there is a general consensus that adverse early
      experiences contribute to adult psychopathology.

PMID- 15958282
TI  - Elucidating effects of long-term expression of HIV-1 Nef on astrocytes by
      microarray, promoter, and literature analyses.
AB  - The challenge of microarray analysis is to unveil the biological mechanisms
      behind the chip data. Due to the sometimes counteracting influences of de novo
      transcription, RNA processing and degradation, the discovery of any particular
      mechanism is difficult. Therefore, a combination of data- and knowledge-driven
      analysis appears to be the best way to attack the problem. We analyzed human
      astrocytes stably expressing the HIV-1 nef gene by microarray analyses to
      elucidate the effects of constitutive HIV-1 Nef expression on the transcriptome
      of astrocytes. Statistical evaluation of microarray results revealed small
      clusters of genes specifically up-regulated by native Nef protein in contrast to
      astrocytes expressing a non-myristoylated Nef variant. At least three
      significantly overrepresented gene ontology groups (small GTPase signaling,
      regulation of apoptosis and lipid metabolism) were detected. The JAK/STAT pathway
      was clearly associated with those genes. This finding agreed well with a
      literature-based approach, where a network was derived by combined literature and
      promoter sequence analysis. Promoter organization suggested potentially
      coordinated transcriptional regulation of some of these genes. Both results were
      in line with previously reported phenotypic changes.

PMID- 15958283
TI  - Characterization of the Bex gene family in humans, mice, and rats.
AB  - To better understand the development of ventral mesencephalic dopamine neurons,
      we performed subtractive hybridization screens to find ventral mesencephalic
      genes expressed at rat embryonic day 10 when these neurons begin to
      differentiate. The most commonly identified genes in these screens were members
      of the Bex (Brain expressed X-linked) gene family, rat Bex1 (Rex3), and a novel
      gene, rat Bex4. After identifying these genes, we then sought to characterize the
      Bex gene family. Two additional novel Bex genes (human Bex5 and mouse Bex6) were
      discovered through genomic databases. Bex5 is present in humans and monkeys, but
      not rodents, while Bex6 exists in mice, but not humans. Bex4 and Bex5 are
      localized to the X chromosome, are expressed in brain, and are similar in
      sequence. Bex4 and Bex5 are 54% and 56% identical to human Bex3 (pHGR74, NADE).
      Mouse Bex6 is on chromosome 16 and is 67% identical to mouse Bex4. Human Bex gene
      expression was studied with tissue expression arrays probed with specific
      oligonucleotides. Human Bex1 and Bex2 have similar expression patterns in the
      central nervous system with high levels in pituitary, cerebellum, and temporal
      lobe, and Bex1 is widely expressed outside of the central nervous system with
      high expression in the liver. Human Bex4 is highly expressed in heart, skeletal
      muscle, and liver, while Bex3 and Bex5 are more widely expressed. The subcellular
      localization of the Bex proteins varies from nuclear (rat Bex1) to cytoplasmic
      (rat Bex3, human Bex5, and mouse Bex6) and to both nuclear and cytoplasmic (rat
      Bex2 and rat Bex4). Rat Bex3, rat Bex4, human Bex5, and mouse Bex6 are degraded
      by the proteasome, while rat Bex1 or Bex2 are not. Rat Bex3 protein can likely
      bind transition metals through a histidine-rich domain. Because this gene family
      was originally named Bex and because these genes are unified by sequence
      similarity and gene structure, we believe the Bex nomenclature should prevail
      over nomenclature based on function (NADE) that has not been extended to the
      other Bex genes. We conclude that the Bex gene family members are highly
      homologous but differ in their expression patterns, subcellular localization, and
      degradation by the proteasome.

PMID- 15958284
TI  - Overlooked blunt bronchial rupture detected by three-dimensional helical-CT.

PMID- 15958285
TI  - NO as a mediator during the early development of the cardiovascular system in the
      zebrafish.
AB  - As a general pattern innervation of the cardiovascular system appears late during
      development in vertebrate embryos, and cardiovascular control may be achieved by
      hormonal activity in early stages. However, very little is known about the onset
      of NO-responsiveness during development, which in adult vertebrates is known to
      play a key function in many physiological processes such as control of vascular
      tone, neurotransmission, macrophage activity, and angiogenesis. Analysis of the
      effect of NO on the cardiovascular system in zebrafish (Danio rerio) embryos and
      larvae revealed almost no effect on cardiac activity during chronic exposure to
      NO-producing chemicals, whereas vascular reactivity was observed in veins and
      arteries of the zebrafish in early developmental stages (5-6 days post
      fertilization). Chronic exposure also modified the development of the vascular
      system. The presence of an NO donor (sodium nitroprusside) did not change the
      patterning of the vascular bed, but it induced an earlier appearance of some
      blood vessels in the trunk region of the zebrafish larvae. The data reveal that
      NO plays an important role in the development of the cardiovascular system and in
      the ontogeny of the cardiovascular control system in fish.

PMID- 15958286
TI  - Cyanide-resistant respiration in Taenia crassiceps metacestode (cysticerci) is
      explained by the H2O2-producing side-reaction of respiratory complex I with O2.
AB  - The nature of the cyanide-resistant respiration of Taenia crassiceps metacestode
      was studied. Mitochondrial respiration with NADH as substrate was partially
      inhibited by rotenone, cyanide and antimycin in decreasing order of
      effectiveness. In contrast, respiration with succinate or ascorbate plus
      N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) was more sensitive to antimycin
      and cyanide. The saturation kinetics for O2 with NADH as substrate showed two
      components, which exhibited different oxygen affinities. The high-O2-affinity
      system (Km app=1.5 microM) was abolished by low cyanide concentration; it
      corresponded to cytochrome aa3. The low-O2-affinity system (Km app=120 microM)
      was resistant to cyanide. Similar O2 saturation kinetics, using succinate or
      ascorbate-TMPD as electron donor, showed only the high-O2-affinity cyanide
      sensitive component. Horse cytochrome c increased 2-3 times the rate of electron
      flow across the cyanide-sensitive pathway and the contribution of the cyanide
      resistant route became negligible. Mitochondrial NADH respiration produced
      significant amounts of H2O2 (at least 10% of the total O2 uptake). Bovine
      catalase and horse heart cytochrome c prevented the production and/or
      accumulation of H2O2. Production of H2O2 by endogenous respiration was detected
      in whole cysticerci using rhodamine as fluorescent sensor. Thus, the CN-resistant
      and low-O2-affinity respiration results mainly from a spurious reaction of the
      respiratory complex I with O2, producing H2O2. The meaning of this reaction in
      the microaerobic habitat of the parasite is discussed.

PMID- 15958287
TI  - Metamizol acts as an ATP sensitive potassium channel opener to inhibit the
      contracting response induced by angiotensin II but not to norepinephrine in rat
      thoracic aorta smooth muscle.
AB  - Clinically metamizol (MZ) has been related to alteration on haemodynamic
      parameters and modifications on blood pressure in humans when administered
      intravenously. These effects have been observed at MZ therapeutic doses.
      Experimentally, MZ is able to induce relaxation on several types of vascular
      smooth muscles and modulates the contraction induced by phenylephrine. However,
      the mechanism underlying the MZ effects on vascular reactivity is not clear.
      Potassium channels (K) present on vascular smooth muscle cells closely regulate
      the vascular reactivity and membrane potential. There are four described types of
      K in vascular tissue: K voltage sensitive (K(V)), K calcium sensitive (K(Ca)2+),
      K ATP sensitive (K(ATP) and K inward rectification (K(IR), voltage sensitive).
      The aim of this work was to investigate MZ effects on angiotensin II (AT II) and
      noradrenaline (NA) induced contraction and to evaluate the K participation on MZ
      modulating effect on vascular smooth muscle contraction, using isometric and
      patch clamp techniques. MZ induces relaxation in a concentration dependent
      manner. Furthermore, MZ strongly inhibits in a concentration dependent fashion
      the contraction induced by AT II. However, MZ inhibition on NA induced
      contraction was moderated compared with that observed on AT II. MZ effects on AT
      II induced contraction was blocked by glybenclamide (a specific K(ATP) blocker, 3
      microM, *p < 0.01). In patch clamp experiments, MZ (3 mM) induces an increase on
      potassium current (K+) mediated by K(ATP) in similar way as diazoxide (a specific
      K(ATP) opener, 3 microM). Our results suggest that MZ induces relaxation and
      inhibits contraction induced by AT II acting as a K(ATP) opener.

PMID- 15958289
TI  - Changes in epidemiology and clinical characteristics of cervical cancer over the
      past 50 years.
AB  - OBJECTIVE: To evaluate the changes in the epidemiology and clinical
      characteristics of cervical cancer over the past 50 years, and explore
      appropriate treatment corresponding to these changes. METHODS: The clinical and
      pathological data of 1557 patients with invasive cervical cancer treated between
      January, 1955 and December, 2004 were retrospectively analyzed. RESULTS AND
      CONCLUSIONS: The average age of cervical cancer onset gradually decreased over
      the past 50 years, from 56.27+/-8.45 in 1955-1964 to 43.81+/-8.9 years in 1995
      2004, whereas the ratio of young (< or =35 years old) patients rose from 3.42% to
      24.91%. The ratio of early clinical stage (stages I-II) and non-squamous cancer
      also steadily increased (P<0.05, respectively). The tumor stage, pathological
      type and rate of lymph node metastasis were all significantly different among
      different age groups (P<0.05). In particular, the young (< or =35 years old)
      group had evidently higher ratios of non-squamous and advanced stage (III-IV)
      cancers with a higher rate of lymphatic metastasis in comparison with other age
      groups (P<0.01, respectively). Because of the changes in epidemiology and
      clinical characteristics of cervical cancer, it is necessary to modify the
      conventional treatment regimens and explore reasonable therapy corresponding to
      these changes. Preservation of reproductive endocrine function ought to be fully
      considered in cervical cancer treatment in women at childbearing age. Neoadjuvant
      intraarterial chemotherapy is an useful method for cervical cancer treatment at
      present.

PMID- 15958288
TI  - Effect of Changtong oral liquid on serum cytokine concentrations in rats with
      postoperative intestinal adhesion.
AB  - OBJECTIVE: To observe the effects of Changtong oral liquid (CTOL) on the serum
      levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)
      beta(1), interleukin (IL)-1beta, IL-4, IL-6 and IL-10 in rats with postoperative
      intestinal adhesions. METHODS: Fifty-four male Sprague-Dawley rats were
      randomized into 6 equal groups, namely the normal control, model, Simo decoction
      (SMD) groups and three CTOL groups of low, moderate, and high doses,
      respectively. Intestinal adhesion was induced in the rats of the groups other
      than the normal control group. The rats in the normal control and model groups
      received intragastric administration of distilled water (10 ml/kg), and those in
      the 4 treatment groups had SMD (10 ml/kg) and CTOL (at 4.3, 8.6 and 17.2 g/kg for
      low, moderate, and high dose groups, respectively). On day 7 after surgery, blood
      samples were obtained from the rats for measurement of serum cytokine levels with
      enzyme-linked immunosorbent assay followed by adhesion grading according to a 5
      grade scale. RESULTS: CTOL evidently reduced the severity of postoperative
      adhesions and decreased the serum levels of the proinflammatory cytokines such as
      TNF-alpha, IL-1beta, TGF-beta(1) and IL-6. However, it had no significant impact
      on serum levels of the anti-inflammatory cytokines IL-4 and IL-10 in rats with
      postoperative adhesion. CONCLUSION: Significant indices for postoperative
      adhesion assessment are established, which provides the experimental basis for
      evaluating clinical therapeutic effects of postoperative adhesions as well as for
      developing new therapeutic drugs.

PMID- 15958290
TI  - Diagnostic and therapeutic value of endoscopic retrograde
      cholangiopancreatography for biliary complications after liver transplantation:
      report of 12 cases.
AB  - OBJECTIVE: To evaluate the diagnostic and therapeutic value of endoscopic
      retrograde cholangiopancreatography (ERCP) for biliary complications after liver
      transplantation. METHOD: ERCP was performed via electronic duodenoscopy in 12
      patients suspected of having biliary complications such as obstructive jaundice
      after orthotopic liver transplantation. RESULTS: ERCP displayed common bile duct
      stenosis or obstruction in 9 cases (including 2 cases with also calculi), common
      bile duct calculi in 2 cases (including 1 complicated by bile duct dilation) and
      intrahepatic bile duct thinning in the donor liver in 1 case. Balloon dilation of
      the common bile duct, calculus removal and metal stent placement in the common
      bile duct was performed in one case. Calculus removal by Oddi sphincterotomy was
      carried out in 3 cases. Nasobiliary catheter placement was performed in 2 cases.
      CONCLUSION: ERCP may serve as the primary modality for diagnosing and treating
      biliary complications after orthotopic liver transplantation with good safety and
      effectiveness in most cases.

PMID- 15958291
TI  - [A modified method of nuclear transfer for investigating early development of
      mouse embryos reconstructed with cumulus cell nuclei].
AB  - OBJECTIVE: To establish a fast, simple, efficient and minimally invasive method
      for nuclear transfer (NT) to study the early development of mouse embryos
      reconstructed with cumulus cell nuclei in vitro. METHODS: With a sharp-tipped
      enucleation needle, an incision approximately 25 mm in length was made in the
      zona pellucida of a rat oocyte, through which the first polar body was removed
      and the metaphase II chromosome-spindle complex was gently aspirated along with a
      minimal volume of the cytoplasm by slightly pressing and vacuum aspiration of the
      oocyte. A cumulus cell nuclei from C57BL/6j mouse, 10-12 mm in diameter, was
      inserted into the perivitelline space of the enucleated oocyte. The fusion of the
      donor-recipient pair was induced by electrofusion and nuclear formation was
      observed. The development of 2-cell, 4- to 8-cell and morula-stage embryos was
      observed after a 72-hour culture of the reconstructed oocytes in vitro. RESULTS:
      The modified NT method enabled one-step removal of the whole nucleus from the
      oocyte with confirmed reliability of complete nuclear removal by Hoechst 33342
      staining of the removed nuclei examined under UV light. The process of
      enucleation took an average time of 15 s, and the survival rate of the enucleated
      oocytes reached 95%. The success rate of 76.7% was achieved for cumulus cell
      nucleus insertion into the zona pellucida of the enucleated oocytes and
      pronucleus formation occurred in 62.2% of the reconstructed oocytes with nuclear
      transfer. After 72 h of culture in vitro of the reconstructed oocytes in CZB
      medium, the percentage of embryos that developed into 2-cell, 4- to 8-cell and
      morula (more than 16 cells) stages were 57.5%, 39.1% and 27.6%, respectively.
      Microsatellite sequences (D7Mit22 and D4Mit204) were amplified from the DNA of
      the reconstructed embryos for identifying their origin, which was proved to be
      C57BL/6j mouse. CONCLUSION: The modified NT method is simple, minimally invasive,
      efficient and practicable to reconstruct mouse embryos with somatic cell nuclei.

PMID- 15958292
TI  - [Effect of Liangge San on lipopolysaccharide-induced nuclear factor kappa B
      activation in cultured mouse macrophages].
AB  - OBJECTIVE: To investigate the effect of Liangge San, a recipe of traditional
      Chinese herbal medicine, on lipopolysaccharide (LPS)-induced nuclear factor kB
      (NF-kB) activation in mouse macrophages cultured in vitro and explore the signal
      transduction mechanism of the detoxifying effect of Liangge San. METHODS: The
      mice were given oral administration of concentrated decoction of Liangge San to
      obtain the drug-containing serum. Macrophages from mouse abdominal cavity were
      collected, incubated and subsequently re-incubated with LPS and the prepared
      serum at different doses. Immunofluorescence method was adopted to examine the
      expression of NF-kB subunit p65 in the nuclei of the macrophages, and the
      fluorescence intensity of p65 expression was measured by laser scanning confocal
      microscope (LSCM). RESULTS: The fluorescence intensity of p65 expression in the
      nuclei of macrophages incubated with LPS for 1 h was significantly increased
      compared with that in the cells without LPS stimulation and Liangge San serum
      treated cells. The fluorescence intensities were significantly decreased in cells
      treated with the inhibitor TLCK and different doses of Liangge San serum in
      comparison with those in LPS-stimulated cells. The fluorescence intensities were
      the lowest in cells treated with TLCK and high-dose Liangge San serum, and the
      cells treated with moderate and low doses of the serum both showed lower
      intensity compared with that of LPS-stimulated cells. p65 expression was similar
      between the macrophages incubated with LPS and those treated with serum that
      contained no Liangge San. CONCLUSIONS: Mouse serum containing Liangge San can
      inhibit LPS-induced p65 expression in mouse macrophages in a dose-dependent
      manner, which may be one of the signal transduction mechanisms of the detoxifying
      effect of Liangge San.

PMID- 15958293
TI  - [Cloning and sequence analysis of human uric acid transporter gene].
AB  - OBJECTIVE: To obtain full-length human urate transporter (hUAT) gene. METHODS:
      Primers was designed according to the sequence of hUAT reported in Genbank. The
      target fragments were obtained by reverse transcriptional (RT) PCR from the mRNA
      extracted from human renal tubular epithelial cell lines (HK-2), followed by
      cloning into pEGFP-C1 plasmid. The cloned fragment was subjected to restriction
      mapping and sequence analysis for confirmation. RESULTS AND CONCLUSION: hUAT gene
      with correct sequence is successfully cloned from HK-2 cells. The restriction
      maps and sequence analysis of the selected clones were consistent with the
      sequence reported in Genbank.

PMID- 15958294
TI  - [Preparation and surface modification of the magnetic fluid as a targeted drug
      carrier].
AB  - Magnetic fluid containing Fe(3)O(4) as mother nucleus was prepared by chemical
      coprecipitation and treated with dextran-70 for surface modification. The dextran
      70-modified magnetic fluid was reacted with 6-bromohexanoic acid and their
      chemical stability was studied, with the structure characterized by using laser
      granulometer, X-ray diffraction, Fourier-transform infrared analysis and
      transmission electron microscopy. The results showed that the magnetic fluid with
      surface modification by dextran-70 exhibited high stability in the presence
      strong alkali or acid. No chemical changes occurred in the magnetic Fe(3)O(4)
      nucleus surrounded by alkali-treated dextran-70 and the organic chain linked to
      the surface dextran rendered the reaction to the anti-cancer drug such as
      mitomycin C possible, suggesting the potential of the preparation as a drug
      carrier.

PMID- 15958295
TI  - [Establishment and application of real-time fluoriescene-based metry polymerase
      chain reaction for hepatitis B virus genotyping].
AB  - OBJECTIVE: To explore a new method for determining hepatitis B virus (HBV)
      genotypes B-D with real-time fluorescence-based PCR. METHODS: The PCR primers and
      probes were designed according to the analysis of 143 complete HBV genomes from
      GenBank and on the basis of a search for genotype-specific nucleotide sequences
      which were conserved in the 3 HBV genotypes. Real-time fluorescence-based PCR was
      performed for HBV genotyping of 128 samples collected from Lanzhou. Three samples
      of each genotype of B, C and D were randomly selected and their S gene was
      sequenced for confirmation of the results of PCR-based method. RESULTS: Real-time
      PCR identified genotype B in 26 (20.3%), genotype C in 92 (71.9%), and genotype D
      in 10 (7.8%) cases. The sequencing results of the S gene of 18 PCR-produced
      clones were in complete consistence with those of fluorescence-based PCR.
      CONCLUSION: The real-time PCR method is convenient, highly sensitive, rapid and
      accurate, especially suitable in clinical and large-scale epidemiological
      studies.

PMID- 15958296
TI  - [Angiotensin-(1-7) modulates fibrinolytic imbalance induced by oxidized low
      density lipoprotein in cultured human umbilical vein endothelial cells].
AB  - OBJECTIVE: To study the effect of angiotensin-(1-7)[Ang-(1-7)]on fibrinolytic
      imbalance induced by oxidized low- density lipoprotein (ox-LDL) in cultured human
      umbilical vein endothelial cells (HUVECs). METHOD: Cultured HUVECs were incubated
      for 24 h in the presence of Ang-(1-7), ox-LDL and A-779 at different
      concentrations either separately or in combination. The final concentrations of
      Ang-(1-7) were 10, 100 and 1,000 nmol/L, and those of ox-LDL were 25, 50 and 100
      mg protein/L. The final concentration of A-779, an Ang-(1-7) receptor antagonist,
      was 100 nmol/L. Tissue plasminogen activator (t-PA) and its inhibitor-1(PAI-1)
      antigen in the medium were determined by enzyme-linked immunosorbent assay
      (ELISA) and their mRNA levels by reverse transcriptional (RT) PCR. RESULTS: Ox
      LDL (25-100 mg protein/L) dose-dependently increased PAI-1 release and up
      regulated PAI-1 gene transcription, but decreased t-PA release and down-regulated
      t-PA gene transcription (P>0.001-0.05). Ang-(1-7) (100-1,000 nmol/L) dose
      dependently decreased PAI-1 release and PAI-1 gene transcription (P>0.01-0.05)
      but had no effect on t-PA release and gene transcription. In the presence of ox
      LDL, Ang-(1-7) lowered the increased levels of PAI-1 and PAI-1 mRNA, and elevated
      the levels of decreased t-PA and t-PA mRNA in the cells (P>0.01-0.05). The
      effects of Ang-(1-7) could be blocked by A-779. CONCLUSION: Angiotensin-(1-7)
      effectively modulates the fibrinolytic imbalance induced by ox-LDL via its
      specific receptor.

PMID- 15958297
TI  - [Cleavage of telomerase RNA component by two DNAzymes and their effects on
      expression of two apoptosis-related genes in human mammary cancer cells].
AB  - OBJECTIVE: To investigate the cleavage of telomerase RNA component (hTR) by two
      DNAzymes and their effects on the expression of two apoptosis-related genes in a
      human mammary cancer cell line (MCF-7). METHODS: Two "10-23" DNAzymes (DzT and
      DzTi) targeted against hTR RNA and their analogues (DzT' and DzTi') were
      synthesized and used to cleave hTR RNA in vitro and in MCF-7 cells. Reverse
      transcriptional (RT) PCR amplification of a hTR DNA fragment and telomerase
      activity assay by PCR-enzyme-linked immunosorbent assay (ELISA) were performed to
      assess the cleavage efficiency. The biological effect of the DNAzymes was
      evaluated by measuring the expression of two apoptosis-related genes (bax-2 and
      bax). RESULTS: The unmodified DNAzyme, DzT, and its modified form, DzTi, which
      had an 3'-inverted thymidine added, could effectively cleave hTR mRNA in vitro.
      After transfection into MCF-7 cells, DzTi exhibited more powerful cleavage
      ability than DzT, and down-regulated the activity of telomerase (P<0.05).
      However, neither DzTi nor DzT displayed significant effect on the growth of the
      cells (P>0.05) and the expression of bax-2 and bax (P>0.05). DzT' and DzTi',
      derived from DzT and DzTi respectively with a base displacement in the conserved
      catalytic motif, did not exhibit notable cleavage effect on hTR RNA either in
      vitro or in the cells. CONCLUSIONS: The synthesized DNAzymes can effectively and
      specifically cleave hTR RNA and decrease the telomerase activity. As a newly
      found catalytic nucleic acid, DNAzymes will play an important role in gene
      therapy studies of tumors.

PMID- 15958298
TI  - [Chondrocyte apoptosis and the expression of Bcl-2, Bax, Fas and iNos in
      articular cartilage in Kashin-Beck disease].
AB  - OBJECTIVE: To investigate the characteristics of chondrocyte apoptosis and
      distribution of Bcl-2, Bax, Fas and iNos expressions in articular cartilage in
      Kashin-Beck disease (KBD). METHODS: Samples of articular cartilage were collected
      from 15 healthy children and 15 children with KBD diagnosed according to the
      Pathological Criteria of KBD Diagnosis in China. Chondrocyte apoptosis was
      detected by TUNEL method, and the articular chondrocytes positive for Bcl-2, Bax,
      Fas and iNos were stained by B-SA immunohistochemistry. RESULTS: The percentage
      of apoptotic chondrocytes positively stained by TUNEL in the middle layer of
      articular cartilage was significantly higher in KBD children than in the control
      group (33.60%+/-2.71% vs 1.33%+/-0.41%, t=11.59, P<0.01). Significant difference
      in Bcl-2, Bax, Fas and iNos expressions was observed between the upper, middle
      and deep layers of the articular cartilage of KBD children (F =73.49-114.42,
      P<0.01), and staining for Bcl-2, Bax, Fas and iNos in KBD children was prominent
      in the upper layer (41.93%+/-12.26%, 45.60%+/-15.78%, 53.60%+/-16.49%, and
      45.47%+/-14.02%, respectively) and the middle layer (14.93%+/-3.50%, 13.87%+/
      4.32%, 23.27%+/-4.83%, and 21.67%+/-6.82%, respectively) of the articular
      cartilage; the percentages of chondrocytes positively stained for Bcl-2, Bax, Fas
      and iNos were significantly higher than those of the control group (t=11.75
      18.65, P<0.01). CONCLUSION: The percentages of apoptotic chondrocytes and
      chondrocytes positive for Bcl-2, Bax, Fas and iNos in the articular cartilage of
      children with KBD are significantly higher than those in healthy children.

PMID- 15958299
TI  - [c-myc gene silencing in K562 cells with RNA interference].
AB  - OBJECTIVE: To study the inhibitory effect of small interfering RNA (siRNA)
      targeting c-myc gene in K562 cells. METHODS: siRNAs targeting the site 1357 of c
      myc mRNA was designed and synthesized. In vitro cultured K562 cells were
      transfected with lipofectamine 2000 and the inhibitory effect was detected by
      reverse transcriptase (RT)-PCR, cell count, MTT assay and fluorescence-activated
      cell sorting. RESULTS: Compared with the negative and blank control group, the
      transfection group showed marked decrease in the c-myc expression and the K562
      cells exhibited increased apoptosis rate. CONCLUSION: RNA interference can
      effectively inhibit c-myc expression and induce apoptosis in K562 cells.

PMID- 15958300
TI  - [Adeno-associated virus-mediated expression of human endostatin and its
      biological activity in vitro].
AB  - OBJECTIVE: To construct the recombinant adeno-associated viral vector containing
      human endostatin gene (rAAV-hEndo) and observe the biological activity of the
      expressed human endostatin in vitro. METHODS: rAAV-hEndo was prepared using a
      helper virus-free packaging system. The rAAV viral genome titer was quantified by
      Taqman real-time PCR, and the endostatin expressed in human umbilical vein
      endothelial cell line ECV304 was detected by immunofluorescence staining. The
      effects of endostatin on ECV340 cells were evaluated by MTT cell proliferation
      assay, cell cycle analysis and terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end-labeling (TUNEL) technique. RESULTS: The viral titer of rAAV-hEndo
      prepared was 2 x 10(12) vg/ml and the vector had an infection efficiency of 98%.
      Immunofluorescence staining showed that the human endostatin protein was
      expressed mainly in the cytoplasm of ECV304 cells, and the proliferation of the
      cells was obviously inhibited by the supernatant of rAAV-hEndo, with a inhibition
      rate of 67.3% 72 h after the addition of the supernatant. ECV304 cells infected
      with rAAV-hEndo were obviously arrested in G(1) phase, and the G(1)-phase cell
      percentage of treatment group were significantly higher than that of control
      group [(72.5+/-4.0)% vs (52.1+/-2.1)%, P<0.01]. ECV304 cells infected with rAAV
      hEndo demonstrated markedly enhanced apoptosis, with a significantly greater
      apoptotic index than that of the control cells [(32.6+/-3.2)% vs (4.2+/-1.9)%,
      P<0.01]. CONCLUSION: rAAV-hEndo can effectively mediate the expression of
      biologically active human endostatin, which may facilitate further study of
      antiangiogenic gene therapy with endostatin for cancers.

PMID- 15958301
TI  - [Inverse iterative correction for translational motion artifact of magnetic
      resonance imaging based on histogram entropy minimization].
AB  - During the acquisition of a magnetic resonance images (MRI), blurring and
      ghosting artifacts caused by the patient's motion can seriously affect the result
      of diagnosis. A novel automatic post-processing strategy, inverse iterative
      correction (IIC), has been developed to suppress MRI artifacts due to the
      object's in-plane rigid-body motion. By means of the proposed histogram-based
      entropy function, IIC method uses two successive steps to reduce the simulated
      motion artifacts: first, the inverse phase errors are added to all possible
      simulated patient's motion directions, and in the second step, the actual
      directions and displacement from the patient's motion are estimated to properly
      correct the phase, hence remove the artifacts after searching all the trial
      directions. To verify its feasibility, the proposed method was used to reduce
      rigid-motion artifacts due to simulated motion in MRI images. The experimental
      results showed that the new algorithm significantly outperforms over the entropy
      auto-focus compensation algorithm on the quality of corrections for the motion
      artifacts and computational cost.

PMID- 15958302
TI  - [Significance of -191G/C single nucleotide polymorphisms in the promoter region
      of ATP-binding cassette transporter gene in coronary artery disease].
AB  - OBJECTIVE: To investigate the effect of -191G/C single nucleotide polymorphisms
      (SNP) in the promoter region of ATP-binding cassette transporter A1(ABCA1) gene
      on plasma lipids and its significance in coronary artery disease (CAD). METHODS:
      By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),
      -191G/C SNP in the promoter region of ABCA1 gene was analyzed in 204 patients
      with CAD and 114 control subjects and the distribution of the -191G/C genotypes
      compared between the two groups and also between different clinical phenotypes of
      CAD. The clinical indexes associated with CAD were also compared between the
      patients with the three genotypes of CAD. RESULTS: The frequency distribution of
      GG, GC, and CC genotypes significantly differed between CAD group and the control
      group, and the former group had obvious higher CC genotype frequency and the C
      allele frequency (P<0.05 and P<0.01, respectively). In CAD patients, the
      frequency distribution of GG, GC, and CC genotypes varied significantly between
      those with acute coronary syndrome (ACS) and those with stable angina pectoris
      (SAP). The CC genotype showed obviously higher frequency in ACS group than in SAP
      group and the C allele was more frequent in the former group (P<0.05 and P<0.01,
      respectively). However, no significant difference was noted in the body mass
      index, total cholesterol, triglyceride, high-density lipoprotein, low-density
      lipoprotein, or very low-density lipoprotein cholesterols between the three
      genotypes. CONCLUSIONS: The -191G/C SNP in the promoter region of ABCA1 is
      associated with increased CAD and the C allele may relate to the stability of CAD
      without detectable changes in plasma lipids.

PMID- 15958303
TI  - [Killing effect of 131I-Herceptin on breast cancer cell lines in vitro].
AB  - OBJECTIVE: To study the specific killing effect of (131)I-labeled Herceptin on
      breast cancer cell lines positive for Her-2 expression. METHODS: Anti-Her-2
      monoclonal antibody Herceptin was labeled with (131)I by means of IODO-GEN, and
      the killing effects of Herceptin on SK-BR-3, MCF-7 and A549 cell lines expressing
      Her-2 were evaluated with MTT assay. RESULTS: (131)I-Herceptin had immunoactivity
      had to that of Herceptin but possessed stronger killing effects on the cell lines
      expressing Her-2 than Herceptin and (131)I used alone (P<0.05). Its killing
      effect on cell lines negative or only weakly positive for Her-2 expression was
      similar to that of (131)I and Herceptin. CONCLUSION: (131)I-Herceptin can
      specifically kill Her-2-positive cancer cells in vitro.

PMID- 15958304
TI  - [Effect of the oil from ganoderma lucidum spores on pathological changes in the
      substantia nigra and behaviors of MPTP-treated mice].
AB  - OBJECTIVE: To investigate the oil from the spores of ganoderma lucidum, a rare
      Chinese herb, on the behaviors and pathological changes in the substantia nigra
      pars compacta (SNpc) in mouse models of Parkinson's disease (PD) induced by MPTP.
      METHODS: C57BL mice were divided into 3 groups, and the ganoderma spores oil +
      MPTP group were treated with ganoderma spores oil for 8 days, together with
      subcutaneous injection of MPTP (30 mg/kg) starting on the third day for 6 days;
      MPTP group were pretreated with normal saline before subcutaneous MPTP injection,
      and the normal control group received pretreatment with normal saline before
      subcutaneous normal saline injection. The behavioral changes of the mice in
      different groups were observed by pole test, dopamine and its metabolic products
      in the striatum determined by HPLC, tyrosine hydroxylase (TH) positive cells
      detected by immunofluorescence method, and expression of TH protein by Western
      blotting. RESULTS: The mice in the ganoderma spores oil + MPTP group presented
      significantly less involuntary movement of the limbs in the pole test than the
      mice in MPTP group. The levels of dopamine and DOPAC in the striatum of ganoderma
      spores oil-treated mice were increased as compared with those in MPTP group. The
      number of surviving TH-positive neurons in SNpc of mice in ganoderma spores oil +
      MPTP group was significantly greater than that in MPTP group, with also
      significantly increased TH protein expression. CONCLUSION: Ganoderma spores oil
      has neuroprotective effect for preventing doparminergic neuron from impairment by
      MPTP.

PMID- 15958305
TI  - [Targeted adhesion of platelet receptor-specific microbubble agent to thrombus in
      vitro].
AB  - OBJECTIVE: To examine the thrombus-targeting effect of platelet receptor-specific
      lipid microbubbles. METHODS: The targeted microbubbles were prepared by coupling
      Arg-Gly-Asp-Ser (RGDS) with the lipid microbubbles, which were added to the
      microthrombus generated by platelet aggregation. The effects of the targeted
      microbubbles on the ultrasonic signal was observed in an artificial thrombus
      model. RESULTS: The targeted microbubbles were adhesive to the microthrombus,
      while the non-targeted microbubbles did not possess this property. The ultrasonic
      signal of the thrombus border was enhanced significantly after the addition of
      the targeted microbubbles. CONCLUSIONS: Platelet receptor-specific microbubbles
      possess significant adhesive property to the thrombus and can improve signal-to
      noise ratio of the thrombus, suggesting the potential value of the targeted
      microbubbles for clinical application in the diagnosis and treatment of thrombus.

PMID- 15958306
TI  - [Analysis and realization of the method for predicting physical pathways of
      allosteric communication in a protein family].
AB  - A fundamental goal in signal transduction study is to understand allosteric
      communication. The authors present hereby a statistical coupling analysis method
      (developed by Steve W. Lockless etc.) for quantitative mapping of the global
      network of amino acid positions in a protein and predicting a set of
      energetically coupled positions, which may constitute the physical pathways of
      allosteric communication in a protein family. Based on MATLAB, the authors
      realized this method and created histograms of amino acid distributions for all
      63 395 entries (as of April 2004) in the Swiss-Prot database of eukaryotic
      proteins and calculated the mean values. The result was similar to that
      calculated by Steve W. Lockless in October 1998.

PMID- 15958307
TI  - [Detection of cytokeratin 19 and thyroperoxidase expressions in the diagnosis of
      thyroid diseases].
AB  - OBJECTIVE: To investigate the value of detecting cytokeratin 19(CK19) and
      thyroperoxidase (TPO) expression in the diagnosis of thyroid diseases including
      thyroid carcinoma, multinodular goiter, adenoma and Hashimoto thyroiditis.
      METHODS: SP immunohistochemistry was used to detect the expressions of CK19 and
      TPO in paraffin-embedded thyroid tissue specimens obtained from 62 patients with
      thyroid carcinoma (30 with papillary carcinomas, 22 with follicular variant of
      papillary carcinomas, and 10 with follicular carcinomas) and 44 with benign
      thyroid diseases (including 22 with multinodular goiters, 14 with adenoma, and 8
      with Hashimoto thyroiditis). RESULTS: CK19 expression was detected in 96.8% of
      the thyroid carcinomas and in 4.5% of benign thyroid diseases, demonstrating a
      significant difference in CK19 expression between the two thyroid diseases
      (P<0.01). TPO expression was found in 100% of benign thyroid disease and in 3.2%
      of thyroid carcinoma, showing also a significant difference between them
      (P<0.01). CONCLUSION: CK19 and TPO can be important molecular markers for
      diagnosing thyroid carcinoma.

PMID- 15958309
TI  - [Effects of macrophage migration inhibitory factor on collagen I and III mRNA
      expression in vascular smooth muscle cells in vitro].
AB  - OBJECTIVE: To investigate the association between macrophage migration inhibitory
      factor (MIF) and collagen synthesis in vascular smooth muscle cells (VSMCs).
      METHOD: VSMCs isolated from SD rat aorta were cultured in different culture
      plates, and the fourth passage of cells were divided into two groups, one of
      which was simulated by MIF and the other served as control group. Collagen I and
      III mRNA expression in the VSMCs was detected by reverse transcriptase (RT)-PCR
      and PCR. RESULT: Collagen I and III mRNA expression in MIF-treated VSMCs
      increased significantly as compared with that in the control cells (P<0.05).
      CONCLUSION: MIF increases collagen I and III mRNA expression of VSMCs in vitro,
      indicating its involvement in collagen synthesis in VSMCs.

PMID- 15958308
TI  - [Determination of cinnamic acid in styrax produced in Guangdong province by
      highperformance liquid chromatography].
AB  - The content of cinnamic acid in styrax produced in Guangdong Province was
      determined by high-performance liquid chromatography. The results indicate that
      the content of total cinnamic acid and free cinnamic acid were 35.85% and 8.05%,
      respectively, which meets the demand of Chinese Pharmacopoeia.

PMID- 15958310
TI  - [Dynamic monitoring of graft-versus-host disease after allogeneic peripheral
      blood stem cell transplantation by soluble HLA-I antigen detection].
AB  - OBJECTIVE: To assess the value of dynamic monitoring of soluble human lymphocytic
      antigen-I (sHLA-I) in the prediction of graft-versus-host disease (GVHD) after
      allogeneic peripheral blood stem cell transplantation (PBSCT). METHOD: Sandwich
      enzyme-linked immunosorbent assay (ELISA) was used to quantitatively detect serum
      sHLA-I. The serum samples for testing were added into W6 32 monoclonal antibody
      coated microtiter plate and incubated with anti-beta2m HRP followed by color
      development with the addition of the substrate. Serum sHLA-I level was measured
      in 63 healthy blood donors of Shanghai and in 24 PBSCT recipients before and and
      at different time points after the operation. RESULT: No changes in sHLA-I levels
      occurred in allogeneic PBSCT recipients without GVHD or with only grade I GVHD,
      but sHLA-I reached high levels in patients suffering GVHD II-IV(P<0.05), which
      was effectively lowered by the application of immunosuppressants. CONCLUSION:
      Measurements of sHLA-I levels can be valuable for monitoring GVHD after PBSCT.

PMID- 15958311
TI  - [Association between angiotensin converting enzyme I/D polymorphism and high
      sensitivity C-reactive protein in type 2 diabetic patients with atherosclerosis
      treated with ramipril].
AB  - OBJECTIVE: To explore the relationship between angiotensin converting enzyme
      (ACE) (I/D) gene polymorphism and the level of high-sensitivity C-reactive
      protein (hsCRP) in type 2 diabetic patients with atherosclerosis treated with
      ramipril. METHODS: A total of 118 in type 2 diabetic patients with
      atherosclerosis aged 35 years or older without clinical proteinuria, heart
      failure, or low ejection fraction (<40%), who were not taking ACE inhibitors or
      (ARB), were randomized into two groups to receive treatment with ramipril (ACEI
      group, beginning with 2.5 mg/d till reaching 5 mg/d) or placebo for 3 months. The
      99 patients in ACEI group were further divided into 3 subgroups according to ACE
      (I/D) genotypes DD, ID and II, each group consisting of at least 20 patients. The
      level of hsCRP was detected by enzyme-linked immunosorbent assay before and after
      the therapy. RESULT AND CONCLUSION: After therapy, hsCRP level significantly
      decreased, but hsCRP levels showed no significant differences between the groups
      of different ACE genotypes.

PMID- 15958312
TI  - [Evaluation of the cardiomyopathies with predominant right ventricular
      involvement by echocardiography].
AB  - OBJECTIVE: To investigate the echocardiographic features of cardiomyopathies with
      predominant right ventricular involvement. METHODS: Echocardiography was used for
      diagnosis of cardiomyopathies with predominant right ventricular involvement in
      13 cases. RESULTS: Obvious right atrial enlargement was observed in 11 patients,
      and all the 13 patients had tricuspid regurgitation of different degrees with
      normal or basically normal left ventricular size. One patient had mild left
      ventricular enlargement. Echocardiography demonstrated in these cases
      characteristic abnormalities of right ventricular cardiomyopathy, classified into
      two types based on the echocardiographic features of the right ventricular
      dilation or apical obliteration. Eight patients had pronounced right ventricular
      dilatation and hypokinesia with right ventricular wall thinning, evident echo
      enhancement and irregularity of the moderator band and right ventricular
      papillary muscles, as well as prominent trabeculations. In the other 5 patients,
      obliterative changes were found in the apical trabecular region of the right
      ventricle, presenting deflated and deformed right ventricle with shrinkage or
      obliteration of the apical trabecular region, increased right ventricular wall
      thickness producing echo enhancement, but the pericardial thickness remained
      normal with normal or dilated right ventricular inflow and outflow tracts.
      CONCLUSIONS: The echocardiographic features of cardiomyopathies with predominant
      right ventricular involvement can be classified into two types, one of which is
      characterized by obviously dilated right ventricle with wall thinning and
      hypokinesia, and the other by obliterative changes in the apical trabecular
      region of the right ventricle with deformed right ventricular cavity, stiffened
      and thickened right ventricular wall with echo enhancement and normal
      pericardium. The echocardiographic characteristics are useful for the diagnosis
      of this disease.

PMID- 15958313
TI  - [Relationship between donor renal graft quality and graft rejection].
AB  - OBJECTIVE: To evaluate the correlation between the quality of donor renal grafts
      and graft rejection. METHODS: The cold ischemia time and the pathological
      findings by biopsies of the donor grafts in 87 cases were analyzed in conjunction
      with the occurrence of acute or chronic graft rejection after transplantation.
      RESULTS: After transplantation, acute rejection occurred in 28 cases, in which 5
      (17.8%) had adverse changes in the donor grafts; chronic allograft nephropathy
      developed in 13 cases, in which 6 (46.1%) had adverse changes in the donor
      grafts. By binary logistic regression analysis, the cold ischemia time and acute
      renal tubular injury were identified as the factors affecting acute graft
      rejection, and cold ischemia time and glomeruloserosis as the risk factors for
      chronic rejection. CONCLUSION: High-quality donor kidney and minimization of the
      risk factors help reduce the occurrence of graft rejection after kidney
      transplantation.

PMID- 15958314
TI  - [Expressions of nuclear factor-kappaB and intercellular adhesion molecule-1 in
      endometriosis].
AB  - OBJECTIVE: To investigate the association of nuclear factor-kappaB (NF-kappaB)
      and intercellular adhesion molecule-1 (ICAM-1) with endometriosis. METHODS:
      Immunohistochemistry was used to examine the NF-kappaB and VEGF protein
      expression in 35 specimens of normal endometrium, 48 eutopic endometrium of
      endometriosis and 76 ectopic endometrium, and the results were analyzed
      statistically. RESULTS: The expressions of NF-kappaB and ICAM-1 were found mainly
      in the glandular epithelial cells of the three endometrium specimens, with the
      ectopic endometriotic tissues showing the highest and normal endometrium the
      lowest expressions (P<0.001). NF-kappaB and ICAM-1 expressions were positively
      correlated to normal, eutopic and ectopic endometrium (r=0.688, 0.773 and 0.777,
      respectively, P<0.01). CONCLUSION: NF-kappaB and ICAM-1 may participate in the
      process of the pathogenesis in endometriosis.

PMID- 15958315
TI  - [Effect of bicyclol tablets on cellular immune responses in patients with chronic
      hepatitis B].
AB  - OBJECTIVE: To study the effect of bicyclol tablets on the levels of interleukin
      (IL)-4, IL-10 and interferon (IFN)-gamma in culture supernatants of peripheral
      blood mononuclear cells (PBMCs) from patients with chronic hepatitis B (CHB).
      METHODS: Whole blood samples were obtained from 30 patients with CHB before and
      at 1 and 3 months during bicyclol tablet therapy and also from 7 healthy donors
      for isolation of the PBMCs. The product of IL-4, IL-10 and IFN-gamma in the
      culture supernatant of PBMCs were determined by enzyme-linked immunosorbent assay
      (ELISA) after 72 h of cultivation. RESULTS: At 3 months during the therapy, the
      level of IFN-gamma was increased significantly in the patients from 36.25+/-19.92
      pg/ml to 53.19+/-7.28 pg/ml (P<0.05) and the level of IL-4 significantly
      decreased from 17.18+/-7.43 pg/ml to 9.74+/-7.75 pg/ml (P<0.01). The changes in
      the levels of IL-4 and IFN-gamma at 3 months during therapy were more obvious in
      patients with HBeAg positivity than in HBeAg-negative patients (8.74+/-6.12 pg/ml
      vs 20.51+/-9.16 pg/ml, 50.71+/-30.76 pg/ml vs 26.03+/-10.48 pg/ml, respectively,
      P<0.05). CONCLUSION: Bicyclol tablets not only promote Th1 type cytokine-mediated
      immune responses but also down-regulates Th2 type cytokine-mediated immune
      responses.

PMID- 15958316
TI  - [Inhibitory effects of integrin av beta3 monoclonal antibody on implanted lesions
      of endometriosis model of SCID mouse].
AB  - OBJECTIVE: To explore the potential use of integrin av beta3 (Lm609) monoclonal
      antibody against ectopic lesion and microvessel angiogenesis of human
      endometriosis xenografts in SCID mice. METHODS: The endometrial tissues from
      endometriosis patients were inoculated subcutaneously into SCID mouse, which were
      treated with Lm609, an inhibitor of angiogenesis, twice a week, for 3 weeks. The
      mice were sacrificed and immunohistochemical staining was employed to determine
      the microvessel density (MVD) and expression of integrin av beta3 in the lesion
      tissues. RESULTS: Lm609 inhibited the growth of the ectopic lesion. The lesion
      weighted 0.82+/-0.09 g in the treated group versus 0.51+/-0.93 g in the control
      group (P<0.05). The MVDs of the treated and control groups were 31.2+/-4.4 and
      14.4+/-1.8 respectively (P<0.05). CONCLUSION: Lm609 can inhibit the growth of
      ectopic lesion by reducing angiogenesis in SCID mouse.

PMID- 15958317
TI  - [Association of S100A4 mRNA expression with differentiation and metastasis of
      renal cell carcinoma].
AB  - OBJECTIVE: To study the association of S100A4 mRNA expression level with the
      differentiation and metastasis of renal cell carcinoma (RCC). METHODS: Tissue
      specimens were obtained from 31 patients undergoing surgery for renal cell
      carcinomas between May 2001 and May 2004. Reverse transcriptional PCR was
      performed for amplification of S100A4 mRNA (212 bp) from 31 RCC tissues and
      matched normal kidney tissues besides the tumor, and the differential S100A4 mRNA
      expression was analyzed for its association with the clinical manifestations of
      the patients. RESULTS: S100A4 mRNA expression was detected in all the RCC tissues
      and normal tissues adjacent to the carcinoma using fluorescence method, and in 29
      cases, S100A4 mRNA expression was significantly higher in the RCC tissues than in
      the matched adjacent tissues. One case had high expressions in both tissues.
      Patients with poorly differentiated RCC had significantly higher S100A4
      expression index than those with well differentiated RCC (7.94 vs 5.06, P<0.001),
      and patients with metastasis also had higher expression index (9.61 vs 5.53,
      P<0.001). No obvious difference was noted in the expression index between
      granular cell tumor and clear cell carcinoma (6.98 vs 6.02, P>0.05). CONCLUSIONS:
      S100A4 may serve as a marker for assessing the progression of RCC and provide
      assistance for clinical therapeutic decisions. S100A4 mRNA expression is
      correlated to RCC differentiation and may facilitate prognostic evaluation of
      RCC. Differential expression of S100A4 mRNA is correlated to the metastasis of
      RCC.

PMID- 15958318
TI  - [Clinical investigation of total intravenous anesthesia with remifentanil and
      propofol for colonoscopy in the elderly].
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravenous anesthesia with
      remifentanil and propofol for colonoscopy in the elderly. METHODS: Thirty old
      patients scheduled for colonoscopy were randomly allocated into remifentanil
      group and fentanyl group. Those in group remifentanil received remifentanil at
      the dose of 0.05 microg/kg.min with micropump, while those in group F were given
      a bolus injection of fentanyl at 1 microg/kg intravenously. One minute later, all
      the patients were given a loading dose of propofol of 0.4 mg/kg followed by
      boluses of propofol (0.2 mg/kg) administered intermittently until Ramsay sedation
      scale III-IV. The induction time of anesthesia, intubation time of colonoscope,
      time of recovery from anesthesia and stay in the postanesthesia care unit (PACU)
      were recorded. The mean arterial pressure (MAP), heart rate (HR), pulse oxygen
      saturation (SpO(2)) and respiratory rate (RR) were measured and recorded with
      noninvasive monitoring. The lower limb movement, apnea, dizziness, body weakness,
      nausea and vomiting, and chest wall rigidity were recorded during operation. All
      the patients were reviewed for satisfaction after the operation. RESULTS: The
      time of anesthesia induction, intubation time of colonoscope, time of recovery
      from anesthesia and stay in PACU in remifentanil group were shorter than those in
      fentanyl group (P<0.05), and propofol consumption was significantly less in the
      former group (P<0.05). Greater MAP decrement was observed in remifentanil group
      (P<0.05). Fewer patients had lower limb movement while more had respiratory
      depression in remifentanil group than in fentanyl group. The rate of patient
      rated satisfaction was significantly higher in remifentanil group (P<0.05).
      CONCLUSION: Intravenous anesthesia with remifentanil and propofol for colonoscopy
      is safe and reliable, which can be a good alternative for anesthesia in
      outpatient operation for the elderly.

PMID- 15958319
TI  - [Therapeutic effect of L-ornithine-L-aspartate on liver cirrhosis complicated by
      hepatic encephalopathy].
AB  - OBJECTIVE: To observe the therapeutic effects of L-ornithine-L-aspartate on liver
      cirrhosis complicated by hepatic encephalopathy. METHODS: Eighty-five patient
      with liver cirrhosis complicated by hepatic encephalopathy were divided into
      therapy group (n=45) and control group (n=40). Patients in the control group were
      treated with routine comprehensive therapy, and those in the therapy group
      received additional intravenous administration with 40 ml L-ornithine-L-aspartate
      in 250 ml 10% glucose and saline (once daily, 7 days for a treatment course).
      RESULTS: L-ornithine-L-aspartase significantly decreased blood ammonia and
      improved hepatic function (P<0.05 or 0.01). The therapeutic effects of therapy
      group was better than that of the control group (P<0.05), and no significant side
      effect was observed in L-ornithine-L-aspartate treatment. CONCLUSION: L-ornithine
      L-aspartate is effective for hepatic encephalopathy and has not obvious side
      effect.

PMID- 15958320
TI  - [Clinical application of abdominal cordocentesis under ultrasound guidance].
AB  - OBJECTIVE: To evaluate the safety and success rate of abdominal cordocentesis
      using a PTC needle under ultrasound guidance. METHODS: Cordocentesis was
      performed under ultrasound guidance in 103 pregnant women with indications of
      prenatal diagnosis. RESULTS: The success rate of cordocentesis was 98.1%
      (101/103). Abnormal chromosome karyotype was detected in 5, intrauterine
      cytomegalovirus infection in 2 and alpha-thalassemia major (Hb Barts disease) in
      3 cases. Severe complications such as miscarriage, fetal death, placental
      abruption or intrauterine infection were not found after the operation.
      CONCLUSION: Abdominal cordocentesis under ultrasound guidance is a safe and
      reliable approach for prenatal diagnosis.

PMID- 15958321
TI  - [Serum S100 protein and radiation-induced brain injury in astrocytoma patients].
AB  - OBJECTIVE: To study the value of serum S100 protein in the diagnosis of radiation
      induced brain injury in astrocytoma patients. METHODS: Serum S100 protein levels
      were detected by enzyme-linked immunosorbent assay in 86 astrocytoma patients in
      the course of radiotherapy. RESULTS: The positivity rates of serum S100 protein
      before, in the middle of and after radiotherapy were 0, 9.3% (8/86) and 19.8%
      (17/86), respectively, showing significant differences (P<0.05) between these
      time points for measurement. CONCLUSION: High levels of serum S100 protein are
      associated with radiation-induced brain injury in astrocytoma patients and may
      serve as the marker for early diagnosis of the injury.

PMID- 15958322
TI  - [Late course three-dimensional conformal radiotherapy in patients with stage III
      non-small cell lung cancer].
AB  - OBJECTIVE: To evaluate the therapeutic efficacy and radiation complications of
      late course three-dimensional conformal radiotherapy (3DCRT) in patients with
      stage III non-small cell lung cancer (NSCLC). METHODS: Eighty-six patients with
      stage III NSCLC were randomly divided into group A (n=42) receiving conventional
      radiotherapy at the total dose of 66 to 70 Gy in 33 to 35 fractions completed in
      6 to 7 weeks and group B (n=44) with late course 3DCRT at the dose of 24-30 Gy in
      6 fractions (400-500 cGy per fraction every other day) after 40 Gy conventional
      radiotherapy, completed in 5 to 6 weeks. RESULTS: The efficacy rates in groups A
      and B were 55.0% and 82.9%, and the complete remission rates were 7.5% and 31.7%
      respectively, showing significant difference between the two groups (P<0.05). The
      1- and 2-year survival rates of the patients in group A and B were 62.5% vs
      78.0%, and 40.0% vs 53.7% respectively, without significant difference (P>0.05).
      The median survival time in groups A and B were 11.4 months and 19.8 months
      respectively. The major radiation complications observed in the two groups were
      grade I to II acute radiation esophagitis and hematopoietic toxicity. The later
      stage radiation complications in the two groups were grade I to II radiation lung
      fibrosis, occurring at a similar rate between the two groups. CONCLUSION: Late
      course 3DCRT produces better therapeutic effects than conventional radiotherapy
      in patients with stage III NSCLC.

PMID- 15958323
TI  - [Relationship between serum vWF and PAF in type 2 diabetic patients and diabetic
      nephropathy].
AB  - OBJECTIVE: To observe the changes in urine albumin (UALB), von Willebrand factor
      (vWF) and platelet-activating factor (PAF) in different courses of type 2
      diabetes. METHODS: Levels of UALB, vWF and PAF were determined in 30 type 2
      diabetic nephropathy patients(group A), type 2 diabetic patients without
      DNP(group B, n=30), patients with impaired glucose tolerance (group C, n=30), the
      first-degree relatives of type 2 diabetic patients with normal glucose
      tolerance(group D, n=30) and 30 normal glucose tolerance subjects without family
      history of type 2 diabetes(group E). RESULTS: UALB and PAF contents were
      significantly higher in group A than in the other groups (P<0.01), while between
      the latter 4 groups, the contents showed no significant differences (P>0.05).
      Serum vWF level was significantly higher in group A than those in the other
      groups (P<0.05). CONCLUSIONS: Renal dysfunction and platelet activation are
      present in type 2 diabetes with microvascular complications, and the synchronized
      changes between renal dysfunction and platelet activation indicate the
      involvement of elevated PAF in vascular injury.

PMID- 15958324
TI  - [Efficacy of complex Hongyibuxue oral solution and ferrous sulfate for iron
      deficiency anemia].
AB  - OBJECTIVE: To observe the efficacy of complex Hongyibuxue oral solution in the
      treatment of iron deficiency anemia (IDA). METHODS: One hundred patients of IDA
      were randomly divided into test group or control group (50 cases each). Patients
      in the test group took complex Hongyibuxue oral solution and those in the control
      group took ferrous sulfate in a treatment course of 4 weeks. RESULTS: Hemoglobin,
      serum iron and serum ferritin in the test group rose faster than those in control
      group (P<0.05). The improvement of the anemic symptoms and tolerance of patients
      to complex Hongyibuxue oral solution in the test group were much better than
      ferrous sulfate. CONCLUSION: The therapeutic effect of and tolerance of patients
      to complex Hongyibuxue oral solution are better than ferrous sulfate in the
      treatment of IDA.

PMID- 15958325
TI  - [Application of intracavitary retrograde dissection in transurethral vaporization
      resection of the prostate].
AB  - OBJECTIVE: To evaluate the effect of intracavitary retrograde dissection during
      transurethral vaporization resection of the prostate (TUVRP). METHODS: The
      efficacy of intracavitary retrograde dissection of the prostate with PK bipolar
      generation was evaluated in 260 cases in view of the volume of intraoperative
      bleeding, operation time, safety and postoperative bleeding, catheterization time
      and prognosis in comparison with the results of exclusive use of TUVRP. RESULTS:
      Intracavitary retrograde dissection of the prostate provided good operative view
      as compared with conventional TUVRP. CONCLUSION: Intracavitary retrograde
      dissection is a practically feasible procedure for benign prostatic hyperplasia.

PMID- 15958326
TI  - [Color Doppler flow imaging for diagnosis of scrotal disease: clinical analysis
      of 76 cases].
AB  - OBJECTIVE: To evaluate the value of color Doppler flow imaging (CDFI) in the
      diagnosis of testicular torsion, epididymitis, testitis, varicocele and
      testicular trauma. METHODS: The morphological changes of the testis and internal
      echo were displayed with two-dimentional ultrasound, and the blood perfusion in
      the testis was observed with color Doppler. The diagnoses were confirmed by
      operation and pathological examination or clinical follow-up. RESULTS: CDFI
      demonstrated reduction or disappearance of blood supply in the testis in 3 cases
      of testicular torsion, and increased blood flow was shown in 8 cases of testitis,
      26 cases of epididymitis and 30 cases of. Nine cases of testicular trauma showed
      some spot-like blood supply or blood supply reduction in the testis. CONCLUSION:
      CDFI is an inexpensive, practicable, reliable, and noninvasive method for
      diagnosing scrotal disease with reproducible results.

PMID- 15958327
TI  - [Surgical management of old vertical unstable pelvic fractures].
AB  - OBJECTIVE: To study the therapeutic effect of open reduction and internal
      fixation in the management of old vertical unstable pelvic fractures. METHODS: In
      the 9 cases with surgical treatment for pelvic fractures, combination of the
      anterior and posterior approaches was adopted. RESULTS: In the follow-up lasting
      for 6-30 months, all pelvic fractures were reduced satisfactorily. The 9 patients
      were able to walk and 8 of them gained good clinical recovery without
      complications. CONCLUSION: In the management of old vertical unstable pelvic
      fractures, a stable pelvis can be reconstructed by effective open reduction and
      internal fixation through combination of the anterior and posterior approaches,
      so that further sequelae can be reduced.

PMID- 15958328
TI  - [Spiral CT findings of pulmonary infection induced by intravenous injection of
      heroin].
AB  - OBJECTIVE: To investigate spiral CT findings of pulmonary infection induced by
      intravenous injection of heroin. METHODS: The clinical data and spiral CT
      findings of 21 patients with pulmonary infection due to intravenous injection of
      heroin were analyzed retrospectively. RESULTS: Pulmonary lesions were detected in
      all these cases in the initial examination by spiral CT plain scan, including
      pneumatocele in 13 (61.9%), pulmonary cavity in 13 (61.9%), pulmonary
      consolidation in 15 (71.4%), and plural lesions in 8 cases (38.1%) of which 7
      (33.3%) had plural effusion and 1 (0.48%) had encapsulated hydropneumothorax.
      Three cases had only one of the lesions and 18 had at least 2 of them. The CT
      images in each case were compared with X-ray film, and the latter displayed
      abnormalities in 20 cases (95.2%). X-ray failed to detect the lesions in 1 case
      (4.8%), in which pneumatocele was found in CT images. CONCLUSION: The pulmonary
      lesions of pulmonary pneumatocele, cavity, consolidation, and plural lesions are
      specific CT manifestations of hematogenous pulmonary suppurative infection
      induced by intravenous injection of heroin.

PMID- 15958329
TI  - [Value of arthroscopy in the diagnosis of acute traumatic cartilage injuries to
      the knee joint].
AB  - We assessed the clinical value of arthroscopy in the diagnosis of acute traumatic
      cartilage injuries of the knee joint in 27 patients. Cartilage fracture was
      detected in the patella in 7, in the femur condyle in 3 and the tibial plateau in
      6 cases. Arthroscopy proves to be a valuable modality for diagnosis of acute
      traumatic cartilage fracture of the knee.

PMID- 15958330
TI  - [Comparison of curative effect of arthroscopic and open surgeries for retrograde
      intramedullary interlocking nails for femoral supracondylar fracture].
AB  - OBJECTIVE: To compare the curative effect of arthroscopic and open surgeries for
      retrograde intramedullary interlocking nails(RIIN) in the treatment of femoral
      supracondylar fracture. METHODS: A total of 40 patients with femoral
      supracondylar fracture underwent either arthroscopic (n=20) or open surgeries
      (n=20) for rRIIN. RESULTS: The operation time, surgical blood loss and bone union
      time in arthroscopic group was less than that in the open surgery group (P<0.05).
      Follow-up of the patients for 10.3+/-3.6 months revealed excellent results in 15
      cases, good in 3 cases, and acceptable in 1 case in the arthroscopic group,
      according to the Kolmert criteria, while excellent in 7, good in 14, acceptable
      in 4 and poor in 2 cases in the open surgery group, without statistically
      significances in the rate of good or excellent outcomes between the two groups
      (90.0% vs 75.0%, P=0.246). CONCLUSION: Compared with open surgery, RIIN shortens
      the operation time, reduces intraoperative blood loss and accelerates bone union,
      thus benefiting the recovery of knee joint functions.

PMID- 15958332
TI  - [Extraction and purification of psoralen from Psoralea corylifolia L].
AB  - OBJECTIVE: To establish a method for extracting psoralen from the seed of
      Psoralea corylifolia L. METHODS: Crushed seed of Psoralea corylifolia L. was
      soaked with 50% ethyl alcohol solution, and the leaching solution was filtrated
      and distilled to remove alcohol. A slurry of the sediment was obtained and
      dissolved in methyl alcohol (MeOH), followed by treatment with active carbon for
      decoloration and evaporation of MeOH, resulting in a lamellar crystal after the
      sediment was kept still overnight. MeOH was applied to dilute the sticky
      solution, and after filteration, a yellow crystal was obtained, recrystallization
      of which in MeOH yielded white needle-like crystals. Thin-layer chromatography
      (TLC) and high-performance liquid chromatography (HPLC) were employed to
      determine the purity of the resultant substance, and UV and H1-NMR applied to
      identify its chemical structure. RESULTS AND CONCLUSION: The resultant crystal is
      confirmed to be pure monomers of psoraren with a yield of 0.147% from the seed
      (m/m) by this simple extraction method.

PMID- 15958331
TI  - [Determination of oxidation-reduction level in patients with rheumatoid
      arthritis].
AB  - OBJECTIVE: To examine the oxidation or reduction products in patients with
      rheumatism arthritis (RA), and investigate the relationship between oxidation or
      reduction products and occurrence and development of RA. METHODS: The serum
      levels of total ascorbic acid (TAA), dehydroascorbic acid (DHAA)/TAA, vitamin E,
      advanced oxidation protein products (AOPP) and malondialdehyde (MDA) were
      detected by high-performance liquid chromatography with electrochemical detection
      in 83 RA patients and 30 healthy adults. Correlation analysis of AOPP, MDA and hs
      CRP was performed. RESULTS: Compared with normal control group, significantly
      higher serum MDA, DHAA/TAA, and AOPP levels were detected in RA patients
      (P<0.05), but vitamin E showed no significant difference (P<0.05). Linear
      regression analysis showed that MDA (P<0.01) was positively but AOPP (P>0.05)
      negatively correlated to hs-CRP. CONCLUSIONS: Oxidation or reduction products in
      serum of RA patients increases significantly, which may be an important mechanism
      for the occurrence and development of RA. Serum AOPP and MDA levels can reflect
      the oxidation status in RA patients.

PMID- 15958333
TI  - [Hemostatic effects of Sorbalgon dressing after intranasal endoscopic surgery].
AB  - OBJECTIVE: To study the therapeutic effects of Sorbalgon dressing for hemostasis
      after intranasal endoscopic surgery. METHODS: Intranasal endoscopic surgery was
      performed in 50 patients with bilateral chronic nasosinusitis and nasal polyps,
      after which the hemostatic effect of Sorbalgon and Vaseline dressings and nasal
      cavity reaction were observed. RESULTS: Sorbalgon dressing resulted in milder
      nasal swelling and pain without obvious nasal hemorrhage and mucous membrane
      reaction, and the average time of nasal recovery was shorter in comparison with
      Vaseline dressing, which caused severe pain, obvious haemorrhage, and nasal
      mucous membrane swelling with prolonged nasal recovery. Three months after the
      operation, similar mucous membrane epithelialization was observed in the nasal
      cavity managed with the two dressings. CONCLUSION: Sorbalgon dressing has good
      hemostatic effect after intranasal endoscopic surgery.

PMID- 15958334
TI  - [Necessity of prophylactic antibiotics in patients with primary liver cancer
      undergoing transcatheter arterial chemoembolization: a prospective study].
AB  - OBJECTIVE: To investigate the necessity of prophylactic administration of
      antibiotic in patients with primary liver cancer undergoing transcatheter
      arterial chemoembolization (TACE). METHODS: Sixty patients without preoperative
      infection were randomized into two groups to receive a single dose of cefazolin
      (PA group) prior to TACE or no prophylactic antibiotics (NONE group). The
      incidence of postoperative infection was compared. RESULTS: The incidence of
      postoperative infection was 3.4% (1/29) in NONE group and 3.2% (1/31) in PA
      group, without significant difference between the two groups (P>0.05).
      CONCLUSION: Prophylactic antibiotics are not necessary for patients with primary
      liver cancer prior to TACE.

PMID- 15958335
TI  - [Effects of self-concept on test anxiety level among sophomores in a medical
      college].
AB  - OBJECTIVE: To explore the effects of self-concept on the test anxiety among
      sophomores in a medical college. METHODS: Using the test anxiety questionnaire
      and English-learning self-concept scale, we examined the relationship between
      test anxiety and self-concept of the sophomores in a medical college. RESULTS:
      All the dimensions of self-concept were significantly related to test anxiety,
      among which the general self-concept, academic self-concept and English-learning
      self concept were important factors. CONCLUSION: Enhancement of general self
      concept, academic self-concept and English-learning self concept are effective
      means to alleviate test anxiety of the students.

PMID- 15958337
TI  - Balanced myocardial ischaemia: a case of "normal" stress Tc99 sestamibi scan and
      diagnosis.

PMID- 15958338
TI  - Multidisciplinary interventions in heart failure.
AB  - A National Service Framework for heart failure is urgently needed.

PMID- 15958339
TI  - Spontaneous triple vessel coronary artery dissection in a patient with effort
      angina.

PMID- 15958340
TI  - The ECG in acute coronary syndromes: new tricks from an old dog.
AB  - The ECG remains the pre-eminent test for myocardial ischaemia, directing
      therapeutic management and prognostic stratification.

PMID- 15958341
TI  - "Sea anemones" on a degenerated bicuspid aortic valve.

PMID- 15958343
TI  - Definition of acute coronary syndrome.

PMID- 15958342
TI  - Prophylactic anticoagulation following the Fontan operation.

PMID- 15958344
TI  - Instructive ECG series in massive bilateral pulmonary embolism.
AB  - The ECG is abnormal in over 70% of patients with pulmonary embolism. Certain ECG
      abnormalities have been observed to return to normal after treatment. This case
      report describes an instructive ECG series in a patient with massive bilateral
      pulmonary embolism as shown by spiral computed tomography. The initial ECG showed
      sinus tachycardia with P pulmonale, although atrial tachycardia could not
      definitively be excluded. The patient had an increased troponin I concentration
      and echocardiographic evidence of right ventricular dysfunction and underwent
      thrombolysis with alteplase and anticoagulation with warfarin. P wave amplitude
      gradually decreased throughout admission and her tachycardia resolved. This may
      reflect a reduction in right atrial strain after treatment. This phenomenon has
      apparently not been described in this setting. The significance of ECG changes
      and the role of thrombolysis in pulmonary embolism are briefly discussed.

PMID- 15958345
TI  - Coronary steal induced by angiogenesis following bypass surgery.

PMID- 15958346
TI  - Endothelial dysfunction and cardiovascular disease: the role of predictive
      adaptive responses.

PMID- 15958349
TI  - Is there a fetal origin of peripheral vascular disease?

PMID- 15958348
TI  - Fetal roots of cardiac disease.

PMID- 15958350
TI  - Response of the fetal heart to changes in load: from hyperplasia to heart
      failure.

PMID- 15958351
TI  - Magnetic resonance imaging diagnosing a left ventricular lipoma in a patient with
      T wave changes on ECG.

PMID- 15958352
TI  - The development of cardiac rhythm.

PMID- 15958353
TI  - Relation between baseline risk and treatment decisions in non-ST elevation acute
      coronary syndromes: an examination of international practice patterns.
AB  - OBJECTIVES: To examine the interaction between ST segment depression on the
      baseline ECG and subsequent in-hospital revascularisation on six month mortality
      among patients with non-ST elevation acute coronary syndromes. To examine whether
      ST segment depression influenced clinical decision making and whether there was
      international variation in the use of cardiac procedures across ST segment
      depression categories. METHODS: 11 453 patients enrolled in GUSTO-IIB (global use
      of strategies to open occluded coronary arteries), PARAGON (platelet IIb/IIIa
      antagonism for the reduction of acute coronary syndrome events in a global
      organisation network) -A, and PARAGON-B were studied. Patients were categorised
      as having no ST segment depression, 1 mm ST segment depression in two contiguous
      leads, and ST segment depression > or = 2 mm in two contiguous leads.
      International practice across four geographic regions was examined: USA, Canada,
      Europe, and Australia/New Zealand. RESULTS: Revascularisation appeared to have no
      impact on survival among patients with no ST segment depression; however,
      revascularisation was associated with a significant survival benefit among
      patients with ST segment depression > or = 1 mm. There was an inverse relation
      between the extent of ST segment depression and the use of angiography as well as
      angioplasty (p < 0.01). However, patients with ST segment depression > or = 2 mm
      were more likely to undergo bypass surgery. The only significant trend of
      increasing use of revascularisation procedures with increasing ST segment
      depression was observed in the USA. CONCLUSIONS: International practice patterns
      in procedure use appear to be insensitive to the extent of ST segment depression.
      Major opportunities for more efficient delivery of care exist in all regions.

PMID- 15958354
TI  - Trends in reperfusion therapy of ST segment elevation myocardial infarction in
      Switzerland: six year results from a nationwide registry.
AB  - OBJECTIVE: To document the trends in reperfusion therapy for ST segment elevation
      myocardial infarction (STEMI) in Switzerland. DESIGN: National prospective
      multicentre registry, AMIS Plus (acute myocardial infarction and unstable angina
      in Switzerland), of patients admitted with acute coronary syndromes. SETTING: 54
      hospitals of varying size and capability in Switzerland. PATIENTS: 7098 of 11 845
      AMIS Plus patients who presented with ST segment elevation or left bundle branch
      block on the ECG at admission. MAIN OUTCOME MEASURES: In-hospital mortality and
      its predictors at admission by multivariate analysis. RESULTS: The proportion of
      patients treated by primary percutaneous coronary intervention (PCI)
      progressively increased from 1997 to 2002, while the proportion with thrombolysis
      or no reperfusion decreased (from 8.0% to 43.1%, from 47.2% to 25.6%, and from
      44.8% to 31.4%, respectively). Overall in-hospital mortality decreased over the
      study period from 12.2% to 6.7% (p < 0.001). Main in-hospital mortality
      predictors by multivariate analysis were primary PCI (odds ratio (OR) 0.52, 95%
      confidence interval (CI) 0.33 to 0.81), thrombolysis (OR 0.63, 95% CI 0.47 to
      0.83), and Killip class III (OR 3.61, 95% CI 2.49 to 5.24) and class IV (OR 5.97,
      95% CI 3.51 to 10.17) at admission. When adjusted for the year, multivariate
      analysis did not show PCI to be significantly superior to thrombolysis for in
      hospital mortality (OR 1.2 for PCI better, 95% CI 0.8 to 1.9, p = 0.42).
      CONCLUSION: Primary PCI has become the preferred mode of reperfusion for STEMI
      since 2002 in Switzerland, whereas use of intravenous thrombolysis has decreased
      from 1997 to 2002. Furthermore, there was a major reduction of in-hospital
      mortality over the same period.

PMID- 15958355
TI  - Cardiomyopathy induced by performance enhancing drugs in a competitive
      bodybuilder.

PMID- 15958356
TI  - Thirty day prognosis of patients with acute pulmonary oedema complicating acute
      coronary syndromes.
AB  - OBJECTIVES: To investigate the characteristics of the acute coronary syndromes
      underlying acute pulmonary oedema and their 30 day prognosis. PATIENTS: 185
      consecutive patients with acute coronary syndromes and acute pulmonary oedema
      admitted to a tertiary care centre. MAIN OUTCOME AND MEASURES: Clinical, ECG,
      echocardiographic, enzymatic, and angiographic features were prospectively
      investigated. RESULTS: Non-ST segment elevation myocardial infarction (NSTEMI)
      was the most frequent cause of acute pulmonary oedema (61%) followed by unstable
      angina (UA; 21%) and ST segment elevation myocardial infarction (STEMI; 18%). In
      each group, mean age was > or = 70 years, but NSTEMI patients were the oldest and
      > or = 65% of patients had chronic hypertension. Moreover, patients with NSTEMI
      and UA were older and had a higher incidence of diabetes, previous myocardial
      infarction, and moderate to severe mitral regurgitation but a similarly reduced
      ejection fraction (NSTEMI, 41%; UA, 39%; and STEMI, 39%) and increased incidence
      of diastolic dysfunction and rate of multivessel disease (94%, 87%, and 86%,
      respectively). However, patients with STEMI had a higher creatine kinase MB peak
      concentration (158 v 76 microg/l in the NSTEMI group, p < 0.001) and 30 day
      mortality (26% v 9% in the NSTEMI group and 8% in the UA group, p < 0.024).
      Multivariate analysis identified ejection fraction < 40% and a peak creatine
      kinase MB concentration > 100 microg/l as the main prognostic markers (p < 0.03).
      CONCLUSIONS: Acute pulmonary oedema is mostly a complication of elderly
      hypertensive patients with NSTEMI or UA (82%) and with multivessel disease often
      associated with mitral regurgitation. On the other hand, the larger infarct size
      and higher mortality in patients with STEMI with a similarly reduced ejection
      fraction suggest a more extensive acute systolic loss.

PMID- 15958357
TI  - Diet in childhood and adult cardiovascular and all cause mortality: the Boyd Orr
      cohort.
AB  - OBJECTIVE: To examine the association between childhood diet and cardiovascular
      mortality. DESIGN: Historical cohort study. SETTING: 16 centres in England and
      Scotland. PARTICIPANTS: 4028 people (from 1234 families) who took part in Boyd
      Orr's survey of family diet and health in Britain between 1937 and 1939 followed
      up through the National Health Service central register. EXPOSURES STUDIED:
      Childhood intake of fruit, vegetables, fish, oily fish, total fat, saturated fat,
      carotene, vitamin C, and vitamin E estimated from household dietary intake. MAIN
      OUTCOME MEASURES: Deaths from all causes and deaths attributed to coronary heart
      disease and stroke. RESULTS: Higher childhood intake of vegetables was associated
      with lower risk of stroke. After controlling for age, sex, energy intake, and a
      range of socioeconomic and other confounders the rate ratio between the highest
      and lowest quartiles of intake was 0.40 (95% confidence interval 0.19 to 0.83, p
      for trend 0.01). Higher intake of fish was associated with higher risk of stroke.
      The fully adjusted rate ratio between the highest and lowest quartile of fish
      intake was 2.01 (95% confidence interval 1.09 to 3.69, p for trend 0.01). Intake
      of any of the foods and constituents considered was not associated with coronary
      mortality. CONCLUSIONS: Aspects of childhood diet, but not antioxidant intake,
      may affect adult cardiovascular risk.

PMID- 15958358
TI  - Systematic review of multidisciplinary interventions in heart failure.
AB  - OBJECTIVE: To determine the impact of multidisciplinary interventions on hospital
      admission and mortality in heart failure. DESIGN: Systematic review. Thirteen
      databases were searched and reference lists from included trials and related
      reviews were checked. Trial authors were contacted if further information was
      required. SETTING: Randomised controlled trials conducted in both hospital and
      community settings. PATIENTS: Trials were included if all, or a defined subgroup
      of patients, had a diagnosis of heart failure. INTERVENTIONS: Multidisciplinary
      interventions were defined as those in which heart failure management was the
      responsibility of a multidisciplinary team including medical input plus one or
      more of the following: specialist nurse, pharmacist, dietician, or social worker.
      Interventions were separated into four mutually exclusive groups: provision of
      home visits; home physiological monitoring or televideo link; telephone follow up
      but no home visits; and hospital or clinic interventions alone. Pharmaceutical
      and exercise based interventions were excluded. MAIN OUTCOME MEASURES: All cause
      hospital admission, all cause mortality, and heart failure hospital admission.
      RESULTS: 74 trials were identified, of which 30 contained relevant data for
      inclusion in meta-analyses. Multidisciplinary interventions reduced all cause
      admission (relative risk (RR) 0.87, 95% confidence interval (CI) 0.79 to 0.95, p
      = 0.002), although significant heterogeneity was found (p = 0.002). All cause
      mortality was also reduced (RR 0.79, 95% CI 0.69 to 0.92, p = 0.002) as was heart
      failure admission (RR 0.70, 95% CI 0.61 to 0.81, p < 0.001). These results varied
      little with sensitivity analyses. CONCLUSION: Multidisciplinary interventions for
      heart failure reduce both hospital admission and all cause mortality. The most
      effective interventions were delivered at least partly in the home.

PMID- 15958359
TI  - Heart failure with preserved left ventricular systolic function: a hospital
      cohort study.
AB  - OBJECTIVE: To investigate how patients with heart failure with preserved left
      ventricular systolic function (LVSF) compare with patients with reduced LVSF.
      DESIGN: Cohort study. SETTING: Urban university hospital. PATIENTS: 528 index
      emergency admissions with heart failure during the year 2000. Information on LVSF
      and follow up was available for 445 (84%) of these patients. RESULTS: 130 (29%)
      patients had preserved LVSF (defined as an ejection fraction > 40%). The median
      follow up was 814 days (range 632-978 days). The average (SD) age was 72 (13)
      years. Women accounted for 62% and 45% of patients with preserved and reduced
      LVSF, respectively (p = 0.001). Patients with preserved LVSF (compared with those
      with reduced LVSF) had a higher prevalence of left ventricular hypertrophy (56% v
      29%) and aortic valve disease (mean gradient > 20 mm Hg; 31% v 9%). Fewer
      patients with preserved LVSF received an angiotensin converting enzyme inhibitor
      (65% v 78%, p = 0.008) or spironolactone (12% v 21%, p = 0.027). Anaemia tended
      to occur more often in patients with preserved LVSF than in those with reduced
      LVSF (43% v 33% for women, p = 0.12; 59% v 49% for men, p = 0.22). There was a
      similarly high prevalence of significant renal dysfunction in both groups
      (estimated glomerular filtration rate < 60 ml/min/1.73 m2 in 68% with preserved
      and 64% with reduced LVSF, p = 0.40). Mortality was similar in both groups
      (preserved versus reduced 51 (39%) v 132 (42%), p = 0.51). Compared with patients
      with reduced LVSF, patients with preserved LVSF tended to have a lower risk of
      death or hospital admission for heart failure (56 (42%) v 165 (53%), p = 0.072)
      but a similar rate of death or readmission for any reason. CONCLUSION: Patients
      with preserved LVSF had more co-morbid problems than those with reduced LVSF;
      however, prognosis was similar for both groups.

PMID- 15958360
TI  - An abnormal ECG with inverted T waves in the precordial leads: confirming the
      diagnosis with contrast enhanced echocardiography.

PMID- 15958361
TI  - Direct comparison of selective endothelin A and non-selective endothelin A/B
      receptor blockade in chronic heart failure.
AB  - OBJECTIVE: To investigate the potential differential effects of selective
      endothelin (ET) A and dual ET-A/B receptor blockade in patients with chronic
      heart failure. METHODS: Nine patients with chronic heart failure (New York Heart
      Association class II-III) each received intravenous infusions of BQ-123 alone
      (selective ET-A blockade) and combined BQ-123 and BQ-788 (dual ET-A/B blockade)
      in a randomised, placebo controlled, three way crossover study. RESULTS:
      Selective ET-A blockade increased cardiac output (maximum mean (SEM) 33 (12)%, p
      < 0.001) and reduced mean arterial pressure (maximum -13 (4)%, p < 0.001) and
      systemic vascular resistance (maximum -26 (8)%, p < 0.001), without changing
      heart rate (p = 0.38). Dual ET-A/B blockade significantly reduced the changes in
      all these haemodynamic variables compared with selective ET-A blockade (p <
      0.05). Selective ET-A blockade reduced pulmonary artery pressure (maximum 25
      (7)%, p = 0.01) and pulmonary vascular resistance (maximum 72 (39)%, p < 0.001).
      However, there was no difference between these effects and those seen with dual
      ET-A/B blockade. Unlike selective ET-A blockade, dual ET-A/B blockade increased
      plasma ET-1 concentrations (by 47 (4)% with low dose and 61 (8)% with high dose,
      both p < 0.05). CONCLUSIONS: While there appeared to be similar reductions in
      pulmonary pressures with selective ET-A and dual ET-A/B blockade, selective ET-A
      blockade caused greater systemic vasodilatation and did not affect ET-1
      clearance. In conclusion, there are significant haemodynamic differences between
      selective ET-A and dual ET-A/B blockade, which may determine responses in
      individual patients.

PMID- 15958362
TI  - Prevalence and clinical significance of systolic impairment in hypertrophic
      cardiomyopathy.
AB  - OBJECTIVES: To determine the frequency of systolic impairment (SI) and its impact
      on the natural history of hypertrophic cardiomyopathy (HCM). METHODS: 1080
      patients (mean (SD) age 43 (15) years, 660 men) with HCM were evaluated. Initial
      assessment included history, examination, 48 hour Holter monitoring,
      cardiopulmonary exercise testing, and echocardiography; SI was defined as a
      fractional shortening (FS) < or = 25%. Survival data were collected at clinic
      visits or by direct communication with patients and their general practitioners.
      The results of serial echocardiography in 462 patients with normal FS at
      presentation are also reported. RESULTS: 26 (2.4%) patients (49 (14) years, 18
      men) had SI at the initial visit. During follow up (58 (49) months), nine (34.6%)
      died or underwent cardiac transplantation compared with 108 (10.2%) patients with
      normal FS (p = 0.01). Five year survival from death (any cause) or
      transplantation was 90.1% (95% confidence interval (CI) 87.8 to 92.4) in patients
      with normal systolic function versus 52.4% (95% CI 25.2 to 79.6, p < 0.0001) in
      patients with SI. In patients who underwent serial echocardiography, 22 (4.8%,
      aged 41 (15) years) developed SI over 66 (40) months; the annual incidence of SI
      was 0.87% (95% CI 0.54 to 1.31). On initial evaluation patients who developed SI
      had a higher frequency of syncope (67 (15.2%) v 10 (45.5%) of those who did not
      develop SI, p = 0.001), non-sustained ventricular tachycardia (91 (20.6%) v 11
      (50%), p = 0.002), and an abnormal blood pressure response on exercise (131
      (29.7%) v 15 (68.2%), p = 0.001). Patients with SI had greater wall thinning (p =
      0.001), left ventricular cavity enlargement (p < 0.0005), and deterioration in
      New York Heart Association functional class (p = 0.001) during follow up.
      Thirteen (59.1%) patients who progressed to SI died or underwent transplantation
      compared with 38 (8.6%) patients who maintained normal systolic function.
      CONCLUSIONS: SI is an infrequent complication of HCM but, when present, is
      associated with a poor prognosis.

PMID- 15958363
TI  - Myocardial cytokine gene expression is higher in aortic stenosis than in
      idiopathic dilated cardiomyopathy.
AB  - OBJECTIVE: To investigate cytokine gene expression in patients with aortic valve
      stenosis (AS) and with idiopathic dilated cardiomyopathy (DCM), and to correlate
      wall stress with myocardial proinflammatory cytokine gene expression. METHODS:
      Human left ventricular (LV) myocardial biopsies were obtained for subsequent
      reverse transcription polymerase chain reaction of tumour necrosis factor alpha
      (TNFalpha), interleukin (IL)-1beta, and IL-6 mRNA. The study population consisted
      of 24 patients with AS and 10 patients with idiopathic DCM. RESULTS: Patients
      with AS had a larger ejection fraction (56 (5) v 37 (4)%, p < 0.01), smaller LV
      end diastolic volumes (146 (11) v 267 (21) ml, p < 0.01), and lower end systolic
      wall stress (44 (7) v 112 (11) kdyn/cm2, p < 0.001). Upregulation of TNFalpha, IL
      1beta, and IL-6 gene expression was detected in both groups. However, TNFalpha
      gene expression was significantly higher in AS than in DCM (p = 0.009). No
      correlation was found between haemodynamic parameters and TNFalpha gene
      expression. In patients with AS there was a strong inverse relation between
      circulating TNFalpha and TNFalpha gene expression (r = -0.685, p = 0.014),
      between circulating TNFalpha and IL-1beta gene expression (r = -0.664, p =
      0.018), and between soluble TNF receptor 2 and TNFalpha gene expression (r = 
      0.685, p = 0.020). Myocardial gene expression of TNFalpha was significantly
      higher in patients with well compensated AS than in patients with decompensated
      AS (p = 0.017). Similarly, patients with decompensated DCM were characterised by
      significantly lower TNFalpha gene expression than were patients with well
      compensated DCM (p = 0.011). CONCLUSION: TNFalpha gene expression is
      significantly higher in patients with pressure overload than in normal hearts, in
      patients with idiopathic DCM, and in patients with compensated versus
      decompensated heart failure. Secondly, in patients with AS proinflammatory
      cytokine gene expression did not affect systolic performance. The higher TNFalpha
      gene expression in patients with compensated heart failure suggests that cytokine
      gene expression has an adaptive role in the early phase of LV remodelling.

PMID- 15958364
TI  - Comparison of clinical and morphological characteristics of Staphylococcus aureus
      endocarditis with endocarditis caused by other pathogens.
AB  - OBJECTIVES: To analyse clinical, echocardiographic, and prognostic
      characteristics of Staphylococcus aureus infective endocarditis (IE) compared
      with endocarditis caused by other pathogens. DESIGN: Cohort study. METHODS: 194
      consecutive patients with definite IE according to the Duke criteria
      prospectively examined by transthoracic and transoesophageal echocardiography
      were enrolled. Patients without identified microorganisms were excluded. The S
      aureus IE group (n = 61) was compared with the group with IE caused by other
      pathogens (n = 133). RESULTS: Compared with IE caused by other pathogens, S
      aureus IE was characterised by severe co-morbidity, a shorter duration of
      symptoms before diagnosis, and a higher prevalence of right sided IE, cutaneous
      portal of entry, and history of renal failure. Severe sepsis, major neurological
      events, and multiple organ failure were more frequent during the acute phase in S
      aureus IE. In-hospital mortality (34% v 10%, p < 0.001) was higher in patients
      with S aureus IE and the 36 month actuarial survival rate was lower in S aureus
      IE than in IE caused by other pathogens (47% v 68%, p = 0.002). Multivariate
      analyses identified S aureus infection as a predictive factor for in-hospital
      mortality and for overall mortality. CONCLUSIONS: S aureus IE compared with IE
      caused by other pathogens occurs in a more debilitated clinical setting and is
      characterised by a higher prevalence of severe sepsis, major neurological events,
      and multiple organ failure leading to higher mortality.

PMID- 15958365
TI  - Spontaneous stent-edge spasm in a patient with myocardial infarction.

PMID- 15958366
TI  - Image quality and diagnostic accuracy of non-invasive coronary imaging with 16
      detector slice spiral computed tomography with 188 ms temporal resolution.
AB  - OBJECTIVE: To evaluate image quality and clinical accuracy in detecting coronary
      artery lesions with a new multidetector spiral computed tomography (MDCT)
      generation with 16 detector slices and a temporal resolution of 188 ms. METHODS:
      124 consecutive patients scheduled for invasive coronary angiography (ICA) were
      additionally studied by MDCT (Sensation 16 Speed 4D). MDCTs were analysed with
      regard to image quality and presence of coronary artery lesions. The results were
      compared with ICA. RESULTS: 120 of 124 scans were successful. The image quality
      of all remaining 120 scans was sufficient (mean (SD) heart rate 64.2 (9.8)
      beats/min, range 43-95). The mean calcium mass was 167 (223) mg (range 0-1038).
      Thirteen coronary segments were evaluated for each patient (1560 segments in
      total). Image quality was graded as follows: excellent, 422 (27.1%) segments;
      good, 540 (34.6%) segments; moderate, 277 (17.7%) segments; heavily calcified,
      215 (13.8%) segments; and blurred, 106 (6.8%) segments. ICA detected 359 lesions
      with a diameter stenosis > 50% and MDCT detected 304 of 359 (85%). Sensitivity,
      specificity, and positive and negative predictive values were 85%, 98%, 91%, and
      96%, respectively. The correct clinical diagnosis (presence or absence of at
      least one stenosis > 50%) was obtained for 110 of 120 (92%) patients.
      CONCLUSIONS: MDCT image quality can be further improved with 16 slices and faster
      gantry rotation time. These results in an unselected population underline the
      potential of MDCT to become a non-invasive diagnostic alternative, especially for
      the exclusion of coronary artery disease, in the near future.

PMID- 15958367
TI  - Long term outcome after intracoronary beta radiation therapy.
AB  - OBJECTIVES: To determine the long term outcome after intracoronary beta radiation
      therapy (IRT). SETTING: Tertiary referral centre. METHODS: The rate of major
      adverse cardiac events (MACE) was retrospectively determined in 301 consecutive
      patients who were treated with IRT. MACE was defined as death, myocardial
      infarction, or any reintervention. Long term clinical outcome was obtained from
      an electronic database of hospital records and from questionnaires to the
      patients and referring physicians. Long term survival status was assessed by
      written inquiries to the municipal civil registries. RESULTS: The mean (SD)
      follow up was 3.6 (1.2) years. The cumulative incidence of MACE at six months was
      19.1%, at one year 36.4%, and at four years 58.3%. The target lesion
      revascularisation (TLR) rate at six months was 12.9%, at one year 28.3%, and at
      four years 50.4%. From multivariate analysis, dose < 18 Gy was the most
      significant predictor of TLR. At four years the cumulative incidence of death was
      3.8%, of myocardial infarction 13.4%, and of coronary artery bypass surgery
      11.3%. Total vessel occlusion was documented in 12.3% of the patients.
      CONCLUSIONS: In the long term follow up of patients after IRT, there are
      increased adverse cardiac events beyond the first six months.

PMID- 15958368
TI  - Anomalous origin of the left coronary artery from the pulmonary artery in an
      elderly patient visualised by three dimensional multidetector CT coronary
      angiography.

PMID- 15958371
TI  - Bulky thrombus associated with patent foramen ovale.

PMID- 15958372
TI  - Helicobacter pylori and atrial fibrillation: a possible pathogenic link.

PMID- 15958369
TI  - The CP stent--short, long, covered--for the treatment of aortic coarctation,
      stenosis of pulmonary arteries and caval veins, and Fontan anastomosis in
      children and adults: an evaluation of 60 stents in 53 patients.
AB  - OBJECTIVE: To evaluate the feasibility and usefulness of the Cheatham platinum
      (CP) stent in a broad spectrum of lesions. METHODS: Retrospective analysis of 60
      implanted CP stents (11-80 mm lengths, 12 covered) between September 2001 and
      March 2004. PATIENTS: 53 patients aged 2.5-68 years (median 17 years). Body
      weight ranged from 12-95 kg (median 52 kg). Thirty six patients had aortic
      (re)coarctation; seven of them had functionally interrupted aortic arches.
      Thirteen patients had pulmonary artery stenosis and four had stenosis of caval
      veins or conduits in a total cavopulmonary connection (TCPC). RESULTS: Arterial
      pressure gradients dropped from 33 mm Hg (range 20-80 mm Hg) to 5 mm Hg (range 0
      10 mm Hg) and pressure gradients in TCPC or caval veins dropped from 4 mm Hg
      (range 4-20 mm Hg) to 0 mm Hg (range 0-3 mm Hg). All stents were placed in the
      target lesion without complications. Three stent fractures without clinical
      instability were noted. CONCLUSIONS: The CP stent is suitable for the treatment
      of vessel stenosis in congenital heart diseases from childhood to adulthood.
      Whether these good results will be stable in the long term needs to be
      investigated.

PMID- 15958370
TI  - Prosthetic valve endocarditis: who needs surgery? A multicentre study of 104
      cases.
AB  - OBJECTIVES: To identify the prognostic markers of a bad outcome in a large
      population of 104 patients with prosthetic valve endocarditis (PVE), and to study
      the influence of medical versus surgical strategy on outcome in PVE and thus to
      identify patients for whom surgery may be beneficial. DESIGN: Multicentre study.
      METHODS AND RESULTS: Among 104 patients, 22 (21%) died in hospital. Factors
      associated with in-hospital death were severe co-morbidity (6% of survivors v 41%
      of those who died, p = 0.05), renal failure (28% v 45%, p = 0.05), moderate to
      severe regurgitation (22% v 54%, p = 0.006), staphylococcal infection (16% v 54%,
      p = 0.001), severe heart failure (22% v 64%, p = 0.001), and occurrence of any
      complication (60% v 90%, p = 0.05). By multivariate analysis, severe heart
      failure (odds ratio 5.5) and Staphylococcus aureus infection (odds ratio 6.1)
      were the only independent predictors of in-hospital death. Among 82 in-hospital
      survivors, 21 (26%) died during a 32 month follow up. A Cox proportional hazards
      model identified early PVE, co-morbidity, severe heart failure, staphylococcus
      infection, and new prosthetic dehiscence as independent predictors of long term
      mortality. Mortality was not significantly different between surgical and non
      surgical patients (17% v 25%, respectively, not significant). However, both in
      hospital and long term mortality were reduced by a surgical approach in high risk
      subgroups of patients with staphylococcal PVE and complicated PVE. CONCLUSIONS:
      Firstly, PVE not only carries a high in-hospital mortality risk but also is
      associated with high long term mortality and needs close follow up after the
      initial episode. Secondly, congestive heart failure, early PVE, staphylococcal
      infection, and complicated PVE are associated with a bad outcome. Thirdly,
      subgroups of patients could be identified for whom surgery is associated with a
      better outcome: patients with staphylococcal and complicated PVE. Early surgery
      is strongly recommended for these patients.

PMID- 15958373
TI  - Carotid intima-media thickness in post-coarctectomy patients with exercise
      induced hypertension.

PMID- 15958375
TI  - Amiodarone infusion in the treatment of acute atrial fibrillation or flutter:
      high versus low dose treatment.

PMID- 15958376
TI  - Syncope in a 29 year old athlete: critical hint from the pulse watch.

PMID- 15958377
TI  - Low prevalence of cardiac troponin T mutations in a Greek hypertrophic
      cardiomyopathy cohort.

PMID- 15958378
TI  - Coronary angiography in the angioplasty era: projections with a meaning.

PMID- 15958379
TI  - Consent in cardiology: there may be trouble ahead?

PMID- 15958380
TI  - Clinical applications of intracardiac echocardiography in interventional
      procedures.

PMID- 15958381
TI  - Human keratinocytes release ATP and utilize three mechanisms for nucleotide
      interconversion at the cell surface.
AB  - Nucleotide activation of P2 receptors is important in autocrine and paracrine
      regulation in many tissues. In the epidermis, nucleotides are involved in
      proliferation, differentiation, and apoptosis. In this study, we have used a
      combination of luciferin-luciferase luminometry, pharmacological inhibitors, and
      confocal microscopy to demonstrate that HaCaT keratinocytes release ATP into the
      culture medium, and that there are three mechanisms for nucleotide
      interconversion, resulting in ATP generation at the cell surface. Addition of
      ADP, GTP, or UTP to culture medium elevated the ATP concentration. ADP to ATP
      conversion was inhibited by diadenosine pentaphosphate, oligomycin, and UDP,
      suggesting the involvement of cell surface adenylate kinase, F(1)F(0) ATP
      synthase, and nucleoside diphosphokinase (NDPK), respectively, which was
      supported by immunohistochemistry. Simultaneous addition of ADP and GTP elevated
      ATP above that for each nucleotide alone indicating that GTP acts as a phosphate
      donor. However, the activity of NDPK, F(1)F(0) ATP synthase or the forward
      reaction of adenylate kinase could not fully account for the culture medium ATP
      content. We postulate that this discrepancy is due to the reverse reaction of
      adenylate kinase utilizing AMP. In normal human skin, F(1)F(0) ATP synthase and
      NDPK were differentially localized, with mitochondrial expression in the basal
      layer, and cell surface expression in the differentiated layers. We and others
      have previously demonstrated that keratinocytes express multiple P2 receptors. In
      this study we now identify the potential sources of extracellular ATP required to
      activate these receptors and provide better understanding of the role of
      nucleotides in normal epidermal homeostasis and wound healing.

PMID- 15958382
TI  - Aberrantly increased hydrophobicity shared by mutants of Cu,Zn-superoxide
      dismutase in familial amyotrophic lateral sclerosis.
AB  - More than 100 different mutations in the gene encoding Cu,Zn-superoxide dismutase
      (SOD1) cause preferential motor neuron degeneration in familial amyotrophic
      lateral sclerosis (ALS). Although the cellular target(s) of mutant SOD1 toxicity
      have not been precisely specified, evidence to date supports the hypothesis that
      ALS-related mutations may increase the burden of partially unfolded SOD1 species.
      Influences that may destabilize SOD1 in vivo include impaired metal ion binding,
      reduction of the intrasubunit disulfide bond, or oxidative modification. In this
      study, we observed that metal-deficient as-isolated SOD1 mutants (H46R, G85R,
      D124V, D125H, and S134N) with disordered electrostatic and zinc-binding loops
      exhibited aberrant binding to hydrophobic beads in the absence of other
      destabilizing agents. Other purified ALS-related mutants that can biologically
      incorporate nearly normal amounts of stabilizing zinc ions (A4V, L38V, G41S,
      D90A, and G93A) exhibited maximal hydrophobic behavior after exposure to both a
      disulfide reducing agent and a metal chelator, while normal SOD1 was more
      resistant to these agents. Moreover, we detected hydrophobic SOD1 species in
      lysates from affected tissues in G85R and G93A mutant but not wildtype SOD1
      transgenic mice. These findings suggest that a susceptibility to the cellular
      disulfide reducing environment and zinc loss may convert otherwise stable SOD1
      mutants into metal-deficient forms with locally destabilized electrostatic and
      zinc-binding loops. These abnormally hydrophobic SOD1 species may promote
      aberrant interactions of the enzyme with itself or with other cellular
      constituents to produce toxicity in familial ALS.

PMID- 15958383
TI  - Epitope mapping of monoclonal antibody to integrin alphaL beta2 hybrid domain
      suggests different requirements of affinity states for intercellular adhesion
      molecules (ICAM)-1 and ICAM-3 binding.
AB  - Integrin undergoes different activation states by changing its quaternary
      conformation. The integrin beta hybrid domain acts as a lever for the
      transmission of activation signal. The displacement of the hybrid domain can
      serve to report different integrin activation states. The monoclonal antibody
      (mAb) MEM148 is a reporter antibody that recognizes Mg/EGTA-activated but not
      resting integrin alpha(L) beta2. Herein, we mapped its epitope to the critical
      residue Pro374 located on the inner face of the beta2 hybrid domain. Integrin
      alpha(L) beta2 binds to its ligands ICAM-1 and ICAM-3 with different affinities.
      Integrin is proposed to have at least three affinity states, and the position of
      the hybrid domain differs in each. We made use of the property of mAb MEM148 to
      analyze and correlate these affinity states in regard to alpha(L)
      beta2/intercellular adhesion molecule (ICAM) binding. Our study showed that
      Mg/EGTA-activated alpha(L)beta2 can adopt a different conformation from that
      activated by activating mAbs KIM185 or MEM48. Unlike ICAM-1 binding, which
      required only one activating agent, alpha(L) beta2/ICAM-3 binding required both
      Mg/EGTA and an activating mAb. This suggests that alpha(L)beta2 with intermediate
      affinity is sufficient to bind ICAM-1 but not ICAM-3, which requires a high
      affinity state. Furthermore, we showed that the conformation adopted by
      alpha(L)beta2 in the presence of Mg/EGTA, depicting an intermediate activation
      state, could be reverted to its resting conformation.

PMID- 15958384
TI  - Compensation for a defective interaction of the hsp70 ssq1 with the mitochondrial
      Fe-S cluster scaffold isu.
AB  - Ssq1, a specialized yeast mitochondrial Hsp70, plays a critical role in the
      biogenesis of proteins containing Fe-S clusters through its interaction with Isu,
      the scaffold on which clusters are built. Two substitutions within the Ssq1
      substrate binding cleft, both of which severely reduced affinity for Isu, had
      very different effects in vivo. Cells expressing Ssq1(F462S), which had no
      detectable affinity for Isu, are indistinguishable from Deltassq1 cells,
      underscoring the importance of the Ssq1-Isu1 interaction in vivo. In contrast,
      cells expressing Ssq1(V472F), whose affinity for Isu is at least 10-fold lower
      than that of wild-type Ssq1, had only moderately reduced Fe-S enzyme activities
      and increased iron levels and grew similarly to wild-type cells. Consistent with
      the reduced affinity for Isu, the ATPase activity of Ssq1(V472F) was stimulated
      less well than that of Ssq1 upon addition of Isu and Jac1, the J-protein partner
      of Ssq1. However, higher concentrations of Jac1 or Isu1, which form a stable
      complex, could compensate for this defect in stimulation of Ssq1(V472F).
      Expression of Isu1 was up-regulated 10-fold in ssq1(V472F) compared with wild
      type cells, suggesting that formation of a Jac1-Isu1 complex can overcome a
      lowered affinity of Ssq1 for Isu in vivo as well as in vitro.

PMID- 15958385
TI  - Generation and characterization of mutant cell lines defective in gamma-secretase
      processing of Notch and amyloid precursor protein.
AB  - Several type I integral membrane proteins, such as the Notch receptor or the
      amyloid precursor protein, are cleaved in their intramembrane domain by a gamma
      secretase enzyme, which is carried within a multiprotein complex. These cleavages
      generate molecules that are involved in intracellular or extracellular signaling.
      At least four transmembrane proteins belong to the gamma-secretase complex:
      presenilin, nicastrin, Aph-1, and Pen-2. It is still unclear whether these
      proteins are the only components of the complex and whether a unique complex is
      involved in the different gamma-secretase cleavage events. We have set up a
      genetic screen based on the permanent acquisition or loss of an antibiotic
      resistance depending on the presence of an active gamma-secretase able to cleave
      a Notch-derived substrate. We selected clones deficient in gamma-secretase
      activity using this screen on mammalian cells after random mutagenesis. We
      further analyzed two of these clones and identified previously undescribed
      mutations in the nicastrin gene. The first mutation abolishes nicastrin
      production, and the second mutation, a point mutation in the ectodomain,
      abolishes nicastrin maturation. In both cases, gamma-secretase activity on Notch
      and APP is impaired.

PMID- 15958386
TI  - Functional metabotropic glutamate receptors on nuclei from brain and primary
      cultured striatal neurons. Role of transporters in delivering ligand.
AB  - G-protein-coupled receptors are well known for converting an extracellular signal
      into an intracellular response. Here we showed that the metabotropic glutamate
      receptor 5 (mGlu5) plays a dynamic intracellular role in signal transduction.
      Activation of endogenously expressed mGlu5 on striatal nuclear membranes leads to
      rapid, sustained calcium (Ca2+) responses within the nucleoplasm that can be
      blocked by receptor-specific antagonists. Extracellular ligands such as glutamate
      and quisqualate reach nuclear receptors via both sodium-dependent transporters
      and cystine glutamate exchangers. Inhibition of either transport system blocks
      radiolabeled agonist uptake as well as agonist-induced nuclear Ca2+ changes.
      Impermeable antagonists like LY393053 and LY367366 not only blocked
      [3H]quisqualate binding but also prevented nontransported agonists such as (RS)
      3,5-dihydroxyphenylglycine from inducing intracellular Ca2+ changes in
      heterologous cells. In contrast, neither LY compound prevented quisqualate or
      glutamate from activating intracellular receptors leading to Ca2+ responses.
      Inasmuch as Ca2+ can enter the nucleoplasm via the nuclear pore complex or from
      the nuclear lumen, the presence of nuclear mGlu5 receptors appeared to amplify
      the latter process generating a faster nuclear response in heterologous cells. In
      isolated striatal nuclei, nuclear receptor activation results in the de novo
      appearance of phosphorylated CREB protein. Thus, activation of nuclear mGlu5
      receptors initiates a signaling cascade that is known to alter gene transcription
      and regulate many paradigms of synaptic plasticity. These studies demonstrated
      that mGlu5 receptors play a dynamic role in signaling both on and off the plasma
      membrane.

PMID- 15958387
TI  - The human apoptosis-inducing protein AMID is an oxidoreductase with a modified
      flavin cofactor and DNA binding activity.
AB  - AMID (apoptosis-inducing factor-homologous mitochondrion-associated inducer of
      death; also known as PRG3 (p53-responsive gene 3)) is a human caspase-independent
      pro-apoptotic protein with some similarity to apoptosis-inducing factor. AMID was
      purified from a recombinant bacterial host, enabling biochemical analysis of the
      protein. AMID is a flavoprotein; possesses NAD(P)H oxidase activity; and
      catalyzes NAD(P)H-dependent reduction of cytochrome c and other electron
      acceptors, including molecular oxygen. NADPH binds approximately 10-fold tighter
      than NADH. AMID binds 6-hydroxy-FAD (a cofactor that accumulates only
      adventitiously and at low abundance in other flavoprotein enzymes) to form a
      stoichiometric cofactor.protein complex. AMID has a distinctive electronic
      spectrum due to the modified flavin. NAD(P)+ binding perturbed the spectrum,
      enabling determination of K(d) values for these coenzymes. 6-Hydroxy-FAD could be
      removed from AMID and the apoprotein reconstituted with FAD. FAD was converted to
      6-hydroxy-FAD in reconstituted AMID during aerobic turnover with NADPH. AMID is a
      DNA-binding protein that lacks apparent DNA sequence specificity. Formation of
      the protein.DNA complex (i) effected a major protein conformational change and
      (ii) was prevented in the presence of nicotinamide coenzyme. Apo-AMID retains DNA
      binding activity. Our studies establish a link between coenzyme and DNA binding
      that likely impacts on the physiological role of AMID in cellular apoptosis.

PMID- 15958388
TI  - Processing of viral DNA ends channels the HIV-1 integration reaction to concerted
      integration.
AB  - Retroviral DNA made by reverse transcription is blunt-ended, and the viral
      integrase protein must remove two nucleotides from each 3' end prior to
      integration into chromosomal DNA. Under most reaction conditions for integration
      in vitro, the majority of the reaction products are "half-site" products that
      result from integration of only one viral DNA end into one strand of the target
      DNA. Preprocessed DNA substrates are more efficient substrates for half-site
      reactions than are blunt-ended substrates, which require the removal of two
      nucleotides prior to integration. In contrast, we find that blunt-ended DNA is a
      better substrate for the biologically relevant reaction of concerted integration
      of pairs of viral DNA ends. The reaction pathway is channeled to concerted
      integration, and half-site integration products are reduced with blunt-ended DNA
      substrate that must first be processed by integrase. In addition, the terminal
      nucleotide requirements for concerted integration are more stringent than for the
      half-site reaction. Longer DNA is more efficient for the concerted reaction than
      is shorter DNA that is capable of efficient half-site integration. This suggests
      that nonspecific interactions of integrase with viral DNA distant from the
      termini contribute to the assembly of a complex that is competent for concerted
      integration. Finally, differential effects of mutation of a residue in the C
      terminal domain of integrase on concerted versus half-site integration implicate
      protein-protein interactions involving this domain as important for concerted
      integration.

PMID- 15958389
TI  - Regulation of homeodomain-interacting protein kinase 2 (HIPK2) effector function
      through dynamic small ubiquitin-related modifier-1 (SUMO-1) modification.
AB  - Homeodomain-interacting protein kinase 2 (HIPK2) is involved in transcriptional
      regulation, growth suppression, and apoptosis. Previous reports showed that HIPK2
      can signal cell death via p53, and independently of p53 by activating the c-Jun
      NH2-terminal kinase (JNK) pathway or mediating CtBP degradation. Here we
      demonstrate that human HIPK2 is small ubiquitin-related modifier-1 (SUMO-1)
      modified in vitro and in vivo at lysine residue 25, a SUMO consensus modification
      motif conserved in human and mouse HIPK family proteins. SUMO modification of
      HIPK2 altered neither its nuclear body localization nor its recruitment to
      promyelocytic leukemia-nuclear bodies. However, SUMO-1 modification inhibited
      HIPK2-induced JNK activation and p53-independent antiproliferative function.
      HIPK2 with a mutated SUMO acceptor lysine residue was refractory to inhibition of
      HIPK2-mediated JNK activation by SUMO-1. Furthermore, we demonstrate that SUMO
      protease SuPr-1 interacts with HIPK2, and both proteins predominantly colocalize
      in promyelocytic leukemia-nuclear bodies. SuPr-1 deconjugates SUMO-1 from HIPK2
      in vitro and in vivo, which results in modestly increased HIPK2-induced JNK
      activity. Thus, our data demonstrate that HIPK2 effector function on JNK is
      modulated through dynamic SUMO-1 modification.

PMID- 15958390
TI  - Physiological regulation of phospholipid methylation alters plasma homocysteine
      in mice.
AB  - Biological methylation reactions and homocysteine (Hcy) metabolism are intimately
      linked. In previous work, we have shown that phosphatidylethanolamine N
      methyltransferase, an enzyme that methylates phosphatidylethanolamine to form
      phosphatidylcholine, plays a significant role in the regulation of plasma Hcy
      levels through an effect on methylation demand (Noga, A. A., Stead, L. M., Zhao,
      Y., Brosnan, M. E., Brosnan, J. T., and Vance, D. E. (2003) J. Biol. Chem. 278,
      5952-5955). We have further investigated methylation demand and Hcy metabolism in
      liver-specific CTP:phosphocholine cytidylyltransferase-alpha (CTalpha) knockout
      mice, since flux through the phosphatidylethanolamine N-methyltransferase pathway
      is increased 2-fold to meet hepatic demand for phosphatidylcholine. Our data show
      that plasma Hcy is elevated by 20-40% in mice lacking hepatic CTalpha. CTalpha
      deficient hepatocytes secrete 40% more Hcy into the medium than do control
      hepatocytes. Liver activity of betaine:homocysteine methyltransferase and
      methionine adenosyltransferase are elevated in the knockout mice as a mechanism
      for maintaining normal hepatic S-adenosylmethionine and S-adenosylhomocysteine
      levels. These data suggest that phospholipid methylation in the liver is a major
      consumer of AdoMet and a significant source of plasma Hcy.

PMID- 15958391
TI  - A combined proteome and microarray investigation of inorganic phosphate-induced
      pre-osteoblast cells.
AB  - Inorganic phosphate, which is generated during osteoblast differentiation and
      mineralization, has recently been identified as an important signaling molecule
      capable of altering signal transduction pathways and gene expression. A large
      scale quantitative proteomic investigation of pre-osteoblasts stimulated with
      inorganic phosphate for 24 h resulted in the identification of 2501 proteins, of
      which 410 (16%) had an altered abundance ratio of greater than or equal to 1.75
      fold, either up or down, revealing both novel and previously defined osteoblast
      regulated proteins. A pathway/function analysis of these proteins revealed an
      increase in cell cycle and proliferation that was subsequently verified by
      conventional biochemical means. To further analyze the mechanisms by which
      inorganic phosphate regulates cellular protein levels, we undertook a mRNA
      microarray analysis of pre-osteoblast cells at 18, 21, and 24 h after inorganic
      phosphate exposure. Comparison of the mRNA microarray data with the 24-hour
      quantitative proteomic data resulted in a generally weak overall correlation; the
      21-hour RNA sample showed the highest correlation to the proteomic data. However,
      an analysis of osteoblast relevant proteins revealed a much higher correlation at
      all time points. A comparison of the microarray and proteomic datasets allowed
      for the identification of a number of candidate proteins that are post
      transcriptionally regulated by elevated inorganic phosphate, including Fra-1, a
      member of the activator protein-1 family of transcription factors. The analysis
      of the data presented here not only sheds new light on the important roles of
      inorganic phosphate in osteoblast function but also begins to address the
      contribution of post-transcriptional and post-translational regulation to a
      cell's expressed proteome. The ability to accurately measure changes in both
      protein abundance and mRNA levels on a system-wide scale represents a novel means
      to extract data from previously one-dimensional datasets.

PMID- 15958392
TI  - Exponentially modified protein abundance index (emPAI) for estimation of absolute
      protein amount in proteomics by the number of sequenced peptides per protein.
AB  - To estimate absolute protein contents in complex mixtures, we previously defined
      a protein abundance index (PAI) as the number of observed peptides divided by the
      number of observable peptides per protein (Rappsilber, J., Ryder, U., Lamond, A.
      I., and Mann, M. (2002) Large-scale proteomic analysis of the human spliceosome.
      Genome. Res. 12, 1231-1245). Here we report that PAI values obtained at different
      concentrations of serum albumin show a linear relationship with the logarithm of
      protein concentration in LC-MS/MS experiments. This was also the case for 46
      proteins in a mouse whole cell lysate. For absolute quantitation, PAI was
      converted to exponentially modified PAI (emPAI), equal to 10PAI minus one, which
      is proportional to protein content in a protein mixture. For the 46 proteins in
      the whole lysate, the deviation percentages of the emPAI-based abundances from
      the actual values were within 63% on average, similar or better than
      determination of abundance by protein staining. emPAI was applied to
      comprehensive protein expression analysis and to a comparison study between gene
      and protein expression in a human cancer cell line, HCT116. The values of emPAI
      are easily calculated and add important quantitation information to proteomic
      experiments; therefore we suggest that they should be reported in large scale
      proteomic identification projects.

PMID- 15958393
TI  - Proteomic identification of insulin-like growth factor-binding protein-6 induced
      by sublethal H2O2 stress from human diploid fibroblasts.
AB  - Fibroblasts are the most ubiquitous cell types within our body. They produce
      various factors to maintain the texture and structure of a particular organ or
      tissue. To identify protein factors secreted by fibroblasts and alteration of
      these protein factors upon oxidative stress, HCA3 human skin diploid fibroblasts
      were exposed to a sublethal dose of H2O2, which induces a prematurely senescent
      phenotype. Conditioned media from prematurely senescent cells versus control
      cells were analyzed for proteins using an LC-MS/MS-based proteomic technique.
      Collagen alpha1(VI), collagen alpha2(I), fibronectin, lumican, and matrix
      metalloproteinase 2 were among the proteins consistently detected from control
      and H2O2-treated cells. Insulin-like growth factor-binding protein-6 (IGFBP-6)
      consistently showed up in the conditioned medium of H2O2-treated cells but not
      from untreated cells. Increased IGFBP-6 production due to H2O2 treatment was
      confirmed by RT-PCR and Western blot analyses. While H2O2 induced a dose
      dependent elevation of IGFBP-6 mRNA, Western blot analyses detected elevated
      levels of IGFBP-6 protein in the conditioned medium of H2O2-treated cells. In
      comparison, fibronectin or matrix metalloproteinase 2 did not show changes at the
      mRNA level in cell lysates or at the protein level in the conditioned medium by
      H2O2 treatment. Using several types of toxins at sublethal doses, including cis
      platin, hydroxyurea, colchicine, L-mimosine, rhodamine, dithiothreitol, or N
      ethylmaleimide, we found that these agents induced increases of IGFBP-6 at mRNA
      and protein levels. An increased level of IGFBP-6 protein was detected in the
      plasma of aging mice and of young mice treated with doxorubicin. These data
      suggest that IGFBP-6 may serve as a sensitive biomarker of cell degeneration or
      injury in vitro and in vivo.

PMID- 15958394
TI  - The long and short of vascular smooth muscle phosphodiesterase-4 as a putative
      therapeutic target.
AB  - In this issue, Tilley and Maurice (p. 596) show that differentiation of vascular
      smooth muscle cells to a proliferative phenotype is associated with a profound up
      regulation of specific phosphodiesterase-4 (PDE4) isoforms because of increased
      histone acetylation. The increased PDE4 activity is seen as preventing cAMP from
      inhibiting the enhanced proliferation, migration, and production of extracellular
      matrix seen in activated VSMC. This Perspective examines the proposal that
      selective inhibition of PDE4D1/2 could find use in adjunctive pharmacotherapy
      after percutaneous coronary interventions and, in addition, discusses the recent
      genetic evidence that PDE4D7 may provide a therapeutic target in stroke.

PMID- 15958396
TI  - Is chromosome analysis mandatory in the initial investigation of normovulatory
      women seeking infertility treatment?
AB  - BACKGROUND: There is no agreement about the frequency of chromosomal
      abnormalities (CAs) in the female partner of an infertile couple and therefore
      there is no evidence base for determining whether karyotype analysis is mandatory
      before the initiation of infertility treatment. The aim of this prospective study
      was to estimate the prevalence of karyotype abnormalities in normovulatory women
      attending an infertility clinic and compare it to that known to be present in the
      newborn female population. METHODS: Cytogenetic testing was performed in 1206
      women with normal ovulatory cycle seeking infertility treatment. At least 15 GTG
      banded metaphases were analysed in each case. In the case of a structural
      abnormality, fluorescent in situ hybridization (FISH) analysis and high
      resolution banding (HRB) were performed on a new blood sample to elucidate the
      aberration. When mosaicism was suspected, the number of analysed metaphases was
      increased to a total of 115 and an additional analysis of 200 metaphases was done
      on a second blood sample. RESULTS: A chromosomal abnormality was demonstrated in
      0.58% (95% CI: 0.28-1.19) of cases which did not differ significantly from that
      reported in female newborns (0.79%; 95% CI: 0.68-0.94). Balanced reciprocal
      translocation was observed in 0.4% of patients (n = 5), paracentric inversion of
      chromosome X in 0.08% (n = 1) and gonosomal mosaicism in 0.08% (n = 1). However,
      chromosomal aberrations were less common among females with primary infertility
      compared to those with secondary infertility (0.25 versus 1.25%, P = 0.04).
      CONCLUSIONS: The present study suggests that routine cytogenetic analysis cannot
      be advocated in normovulatory infertile women. Nevertheless, the relatively
      higher frequency of abnormal karyotypes in women with secondary infertility
      indicates that this subgroup of patients might benefit from a routine karyotype
      analysis.

PMID- 15958395
TI  - Simvastatin has deleterious effects on human first trimester placental explants.
AB  - BACKGROUND: Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG
      CoA reductase), the rate-limiting enzyme of the mevalonate pathway, and have been
      used successfully in the treatment of hypercholesterolaemia. Animal models have
      provided evidence for the teratogenic effects of statins on pregnancy outcome.
      Thus statins are contraindicated during pregnancy. However, conflicting data are
      available from inadvertent use of statins in human pregnancy. Therefore we
      decided to explore the effects of simvastatin on the placenta in an in vitro
      human placental model. METHODS: Human first trimester placental explants that
      were grown on matrigel were exposed to medium supplemented with simvastatin.
      Migration of extravillous trophoblast cells was assessed by visual observation.
      Proliferative and apoptotic events of the trophoblast cells were assesed by
      immunohistochemical examination using anti-Ki67 and anti-activated caspase-3
      antibodies respectively. Hormone levels were measured. RESULTS: Simvastatin
      sharply inhibited migration of extravillous trophoblast cells from the villi to
      the matrigel (P < 0.05). Moreover, simvastatin inhibited half of the
      proliferative events in the villi (P < 0.05) and increased apoptosis of
      cytotrophoblast cells compared to control. Moreover, simvastatin significantly
      decreased secretion of progesterone from the placental explants (P < 0.01).
      CONCLUSION: Simvastatin adversely affects human first trimester trophoblast.

PMID- 15958397
TI  - Effects of vasectomy on spermatogenesis and fertility outcome after testicular
      sperm extraction combined with ICSI.
AB  - BACKGROUND: Each year 40,000 men have a vasectomy in the UK whilst another 2400
      request a reversal to begin a second family. Sperm can now be obtained by
      testicular biopsy and subsequently used in assisted conception with ICSI. The
      study aims were to compare sperm yields of men post-vasectomy or with obstructive
      azoospermia (OA) of unknown aetiology with yields of fertile men and to assess
      any alteration in the clinical pregnancy rates after ICSI. METHODS: Testicular
      tissue was obtained by Trucut needle from men who had undergone a vasectomy >5
      years previously or had OA from other causes and from fertile men during
      vasectomy. Seminiferous tubules were milked to measure sperm yields. Numbers of
      Sertoli cells and spermatids and thickness of the seminiferous tubule walls were
      assessed using quantitative computerized analysis. RESULTS AND CONCLUSIONS: Sperm
      yields/g testis were significantly decreased in men post-vasectomy and in men
      with OA, relative to fertile men. Significant reductions were also observed in
      early (40%) and mature (29%) spermatid numbers and an increase of 31% was seen in
      the seminiferous tubule wall (basal membrane and collagen thickness) of
      vasectomized men compared with fertile men. Clinical pregnancy rates in couples
      who had had a vasectomy were also significantly reduced.

PMID- 15958398
TI  - Slow controlled-rate freezing of sequentially cultured human blastocysts: an
      evaluation of two freezing strategies.
AB  - BACKGROUND: To optimize blastocyst cryopreservation, the prerequisite is to
      develop a better understanding of factors that influence their survival and
      implantation potential. Therefore, the aim of the present work was to evaluate,
      retrospectively, the outcome of blastocyst cryopreservation in a day 2/3 fresh
      embryo transfer programme. METHODS: Two different freezing strategies were
      compared: a first strategy (strategy A: 3007 blastocysts frozen) consisted of
      freezing those blastocysts that had at least a cavity; a second strategy
      (strategy B: 3831 blastocysts frozen) consisted of freezing only more advanced
      stage blastocysts with a good quality inner cell mass and trophectoderm. The
      outcome of cryopreservation, as related to the two different freezing strategies,
      was analysed. In addition, after freezing and thawing, we evaluated the influence
      of blastocyst developmental characteristics on immediate morphological survival
      and further development in vitro. RESULTS: The immediate morphological survival
      after thawing was higher for early blastocysts as compared to advanced and
      hatching blastocysts. The further developmental potential in vitro of thawed
      blastocysts was higher for advanced and hatching blastocysts as compared to early
      blastocysts. As a result, the percentage of deliveries, calculated as a
      percentage of started thawing cycle, and the percentage of children born,
      calculated as a percentage of embryos transferred, was not different for
      strategies A and B. CONCLUSION: The results clearly indicate that culture
      conditions and cryopreservation procedures of blastocysts need to be further
      improved.

PMID- 15958399
TI  - A randomized controlled trial evaluating metformin pre-treatment and co
      administration in non-obese insulin-resistant women with polycystic ovary
      syndrome treated with controlled ovarian stimulation plus timed intercourse or
      intrauterine insemination.
AB  - BACKGROUND: There are few data in the literature regarding the utility of
      metfomin before and during gonadotrophin administration in women with polycystic
      ovary syndrome (PCOS). The aim of the present study was to assess the effect of
      the pre-treatment and co-administration of metformin in infertile PCOS women
      treated with controlled ovarian stimulation (COS) followed by timed intercourse
      (TI) or intrauterine insemination (IUI). METHODS: Seventy insulin-resistant
      primary infertile women with PCOS were randomized to receive metformin cloridrate
      (850 mg twice daily; group A) or placebo tablets (two tablets daily; group B) for
      3 months. Three trials of COS using highly purified urinary FSH (hpFSH) plus
      TI/IUI were performed. Number of ampoules of gonadotrophin used, duration of the
      ovarian stimulation, cycle cancellation, ovulation, pregnancy, abortion, live
      birth, mono-ovulatory cycles, multiple pregnancies and ovarian hyperstimulation
      syndrome (OHSS) rates were assessed. RESULTS: No difference between groups was
      detected in ovulation, cycle cancellation, pregnancy, abortion, live birth,
      multiple pregnancies and OHSS rates. The mono-ovulatory cycle rates were
      significantly (P = 0.002) more frequent in group A than in group B, whereas the
      days of stimulation for non-cancelled cycles and the number of vials of
      gonadotrophins used were significantly (P < 0.001) higher in group A than in
      group B. CONCLUSION: In insulin-resistant women with PCOS, metformin pre
      treatment and co-administration with hpFSH increases the mono-ovulatory cycles.

PMID- 15958400
TI  - Exogenous granulocyte-macrophage colony-stimulating factor promotes follicular
      development in the newborn rat in vivo.
AB  - BACKGROUND: Expression and selective cellular localization of granulocyte
      macrophage colony-stimulating factor (GM-CSF) and its receptor in ovarian tissue
      imply an autocrine/paracrine role in ovarian function. Evidence indicating a
      functional role for GM-CSF in ovarian follicular cell function has been provided
      by studies with GM-CSF knockout (GM-/-) mice, which suggest that GM-CSF
      influences events associated with murine follicular maturation. METHODS: Immature
      female rats were treated with GM-CSF, FSH or saline for 5 or 10 days. Ovaries
      were collected for histologic examination and immunostaining determination of
      CYP17, a theca cell marker. In addition, ovarian section slides were evaluated by
      immunofluorescence for CD45, an ovarian leukocyte marker. To investigate the
      possible mechanism of GM-CSF action on follicular development, theca-interstitial
      cells (T-I) were separated and cultured. Cells were treated with increasing
      concentrations of GM-CSF, then evaluated for CYP17 mRNA and protein expression
      assays. RESULTS: After 10 days of treatment with GM-CSF, the number of small
      preantral and large preantral follicles was significantly increased compared with
      the control group (P < 0.05). Similarly, treatment with FSH increased the number
      of small preantral and large preantral follicles (P < 0.05). CD45 expression
      measured by immunofluorescence was not different in the three groups, indicating
      that the distribution of leukocytes was unchanged. In addition, CYP17 was
      increased in the T-I cells both in vivo and in vitro after GM-CSF treatment.
      CONCLUSION: The present results suggest that GM-CSF may play a significant role
      in follicular development.

PMID- 15958401
TI  - The 'wish to have a child', childlessness and infertility in Germany.
AB  - BACKGROUND: Based on the declining birth rates in Germany, one might assume that
      the number of people who unintentionally are without children is growing.
      However, studies over recent years have documented that the number of people who
      deliberately have no children is growing instead. METHODS: This report focuses on
      attitudes and motives which influence the realization of the desire to have a
      child. In a representative survey, 785 women and 795 men were questioned about
      their current wish to have a child, their ideal number of children and the
      motives for or against the decision to have a child. RESULTS AND CONCLUSIONS:
      Emotional aspects are the most important motives in favour of having children,
      and financial restraints are most frequently cited as arguments against
      parenthood in German society. Thus, deciding in favour or against having children
      still appears to be an indicator of social disparity, due to the fact that every
      realized child wish underlines the differences between parents and childless
      individuals through the increasing financial burdens. As a large number of
      individuals and couples in Germany postpone realization of their desire to have a
      child, this may lead to a change from a voluntary to an involuntary childlessness
      in the individual decision process. Therefore, education about fertility as a
      resource should be promoted.

PMID- 15958402
TI  - World Health Organization grade 'a' motility and zona-binding test accurately
      predict IVF outcome for mild male factor and unexplained infertilities.
AB  - BACKGROUND: The aim of this study was to determine the pronostic value of a sperm
      zona pellucida (ZP) binding assay, combined with World Health Organization (WHO)
      grade 'a' sperm motility on the day of the IVF attempt, to predict sperm
      fertilizing ability in unexplained and moderate male factor infertilities.
      METHODS: In total, 84 couples (64 unexplained infertility; 20 male factor)
      underwent both a sperm-ZP binding assay and an IVF attempt, irrespective of the
      test's result. The test was negative when grade 'a' motility was #5% and/or the
      ZP binding index was <0.7. Fertilization and pregnancy rates were related to the
      test's results. RESULTS: Thirty-one patients had a negative test (group N) and 53
      a positive test (group P). A difference was observed concerning the fertilization
      rate [median (range): 0 (0-75%) versus 50 (0-100%); P = 0.0001] and the number of
      cycles with fertilization rate <20% (65 versus 23%; P = 0.0002) between groups N
      and P respectively. In the group of unexplained and male factor infertilities,
      the test showed a sensitivity of 83 and 60%, specificity of 50 and 90%, positive
      predictive value of 76 and 86%, and negative predictive value of 61 and 69%
      respectively. CONCLUSION: Sperm-ZP binding test, combined with WHO grade 'a'
      motility assessment, is relevant to prevent IVF fertilization failures in
      unexplained infertility and, most particularly, in moderate male factor
      infertility.

PMID- 15958403
TI  - 'The presence of blood in the transfer catheter negatively influences outcome at
      embryo transfer'.

PMID- 15958404
TI  - 'Efficient treatment of infertility due to sperm DNA damage by ICSI with
      testicular sperm'.

PMID- 15958405
TI  - The effects of the human immunodeficiency virus on semen parameters and
      intrauterine insemination outcome.

PMID- 15958406
TI  - Request for information on unreported cases of severe ovarian hyperstimulation
      syndrome (OHSS).

PMID- 15958407
TI  - Recurrent miscarriage and embryonic loss.

PMID- 15958408
TI  - Feeding habits of children with Down's syndrome living in Riyadh, Saudi Arabia.
AB  - The aim of the study was to investigate the breastfeeding and introduction of
      solid foods among children with Down's syndrome. Mothers of 225 children
      attending three institutes providing education for children with Down's syndrome
      were asked to complete a questionnaire. Data were collected on knowledge of
      feeding procedure, pattern of feeding, and introduction of solid food. Although
      66.7% of mothers commenced breastfeeding, 30% of them discontinued breastfeeding
      at 3-6 months of the child's age. Overall, mothers of children with Down's
      syndrome started weaning between 6 and 9 months of age and the formula most used
      was Similac 'yellow'. In conclusion it was observed that Saudi mothers with
      Down's syndrome children frequently breastfed their children and introduced solid
      food comparatively late.

PMID- 15958409
TI  - Anal Albendazole application for pruritus ani in threadworm infestation.

PMID- 15958410
TI  - Immunogenicity and reactogenicity of an indigenous combined diphtheria, tetanus,
      whole-cell Bordetella pertussis and hepatitis B vaccine in Indian infants.

PMID- 15958411
TI  - The impact of a package of single mega dose of vitamin A and daily
      supplementation of iron, folic acid and vitamin C in improving hemoglobin levels.

PMID- 15958412
TI  - Body mass index values in Turkish schoolchildren aged 7-18 years.

PMID- 15958413
TI  - Nipple diameter in eastern Turkish pubertal boys.

PMID- 15958414
TI  - The size of the C-chain maltosaccharide of glycogen: evidence for the presence of
      only a single branch.
AB  - Glycogen is found in mammals and yeast bound to glycogenin forming
      proteoglycogen. The branched polysaccharide is joined to the protein through the
      C-chain, a maltosaccharide considered to be 13 glucose units long and double
      branched as the other branched glycogen B-chains. We described before the
      isolation of c-glycogenin, the debranched C-chain bound to glycogenin, from
      muscle proteoglycogen. In this work, the size of the C-chain is analyzed for the
      first time. The maltosaccharide moiety of c-glycogenin was auto[14C]glucosylated
      by a short incubation with UDP-[14C]glucose, and the labeled maltosaccharide was
      released by heating in 2 M NaOH containing 0.1 M NaBH4 and analyzed by high
      performance thin layer chromatography (HPTLC). The results indicate that the C
      chain is about half the size of the B-chains, not long enough to be double
      branched.

PMID- 15958415
TI  - Dynamic properties of biologically active synthetic heparin-like hexasaccharides.
AB  - A complete study of the dynamics of two synthetic heparin-like hexasaccharides, D
      GlcNHSO3-6-SO4-alpha-(1-->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-(1
      ->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-(1-->4)-L-IdoA-2-SO4-alpha
      1-->iPr (1) and -->4)-L-IdoA-2-SO4-alpha-(1-->4)-D-GlcNHAc-6-SO4-alpha-(1-->4)-L
      IdoA-alpha-(1-->4)-D-GlcNHSO3-alpha-(1-->4)-L-IdoA-2-SO4-alpha-1-->iPr (2), has
      been performed using 13C-nuclear magnetic resonance (NMR) relaxation parameters,
      T1, T2, and heteronuclear nuclear Overhauser effect (NOEs). Compound 1 is
      constituted from sequences corresponding to the major polysaccharide heparin
      region, while compound 2 contains a sequence never found in natural heparin. They
      differ from each other only in sulphation patterns, and are capable of
      stimulating fibroblast growth factors (FGFs)-1 induced mitogenesis. Both
      oligosaccharides exhibit a remarkable anisotropic overall motion in solution as
      revealed by their anisotropic ratios (tau /tau||), 4.0 and 3.0 respectively. This
      is a characteristic behaviour of natural glycosaminoglycans (GAG) which has also
      been observed for the antithrombin (AT) binding pentasaccharide D-GlcNHSO3-6-SO4
      alpha-(1-->4)-D-GlcA-beta-(1-->4)-D-GlcNHSO3-(3,6-SO4)-alpha-(1-->4)-L-IdoA-2-SO4
      alpha-(1-->4)-D-GlcNHSO3-6-SO4-alpha-1-->Me (3) (Hricovini, M., Guerrini, M.,
      Torri, G., Piani, S., and Ungarelli, F. (1995) Conformational analysis of heparin
      epoxide in aqueous solution. An NMR relaxation study. Carbohydr. Res., 277, 11
      23). The motional properties observed for 1 and 2 provide additional support to
      the suitability of these compounds as heparin models in agreement with previous
      structural (de Paz, J.L., Angulo, J., Lassaletta, J.M., Nieto, P.M., Redondo
      Horcajo, M., Lozano, R.M., Jimenez-Gallego, G., and Martin-Lomas, M. (2001) The
      activation of fibroblast growth factors by heparin: synthesis, structure and
      biological activity of heparin-like oligosaccharides. Chembiochem, 2, 673-685;
      Ojeda, R., Angulo, J., Nieto, P.M., and Martin-Lomas. M. (2002) The activation of
      fibroblast growth factors by heparin: synthesis and structural study of
      rationally modified heparin-like oligosaccharides. Can. J. Chem,. 80, 917-936;
      Lucas, R., Angulo, J., Nieto, P.M., and Martin-Lomas, M. (2003) Synthesis and
      structural studies of two new heparin-like hexasaccharides. Org. Biomol. Chem.,
      1, 2253-2266) and biological data (Angulo, J., Ojeda, R., de Paz, J.L., Lucas,
      R., Nieto, P.M., Lozano, R.M., Redondo-Horcajo, M., Gimenez-Gallego, G., and
      Martin-Lomas, M. (2004) The activation of fibroblast growth factors (FGFs) by
      glycosaminoglycans: influence of the sulphation pattern on the biological
      activity of FGF-1. Chembiochem, 5, 55-61). Fast internal motions observed for the
      less sulphated compound 2, as compared with 1, may be related to their different
      behavior in stimulating FGF1-induced mitogenic activity.

PMID- 15958416
TI  - Gastrointestinal mucins of Fut2-null mice lack terminal fucosylation without
      affecting colonization by Candida albicans.
AB  - Posttranslational modification of apomucins by the sequential action of
      glycosyltransferases is required to produce mature mucins. The Secretor gene
      (FUT2) encodes an alpha(1,2)fucosyltransferase (EC 2.4.1.69) that catalyzes
      addition of terminal alpha(1,2)fucose residues on mucins and other molecules in
      mucosal epithelium. Mutant mice containing targeted replacement of Fut2 with the
      bacterial reporter gene lacZ were studied to determine the affect of the loss of
      Fut2 on glycosylation of mucins in the gastrointestinal tract. By whole organ X
      gal staining, lacZ activity is prominently expressed in the foveolar pit and
      chief cells of the glandular stomach, Brunner's glands of the duodenum, and
      goblet cells in the large intestine of Fut2-LacZ-null mice. Staining with Aleuria
      aurantia agglutinin demonstrates loss of L-fucosylated epithelial glycans
      throughout the gastrointestinal tract of Fut2-LacZ-null mice, however, histologic
      appearance of the tissues appears normal. Analysis of oligosaccharides released
      from insoluble colonic mucins, largely Muc2, by mass spectrometry shows complete
      lack of terminal fucosylation of O-linked oligosaccharides in Fut2-LacZ-null
      mice. Precursor glycans accumulate with no evidence of compensation by other
      fucosyltransferases or sialyltransferases on mucin glycosylation. Because Candida
      albicans has been reported to adhere to intestinal mucins creating a potential
      reservoir associated with vaginitis, Fut2-LacZ-null and wild-type mice were
      inoculated by gastric lavage with C. albicans. We observe no difference in
      colonization between genotypes suggesting mucin terminal fucosylation does not
      significantly influence C. albicans-host interaction in the intestine,
      highlighting that infections caused by the same organism at different mucosal
      surfaces are not equal.

PMID- 15958417
TI  - Characterization of the LARGE family of putative glycosyltransferases associated
      with dystroglycanopathies.
AB  - The Large(myd) mouse has a loss-of-function mutation in the putative
      glycosyltransferase gene Large. Mutations in the human homolog (LARGE) have been
      described in a form of congenital muscular dystrophy (MDC1D). Other genes (POMT1,
      POMGnT1, fukutin, and FKRP) that encode known or putative glycosylation enzymes
      are also causally associated with human congenital muscular dystrophies. All
      these diseases are associated with hypoglycosylation of the membrane protein
      alpha-dystroglycan (alpha-DG) and consequent loss of extracellular ligand
      binding. Hence, they are termed dystroglycanopathies. A paralogous gene for LARGE
      (LARGE2 or GYLTL1B) may also have a role in DG glycosylation. Using database
      interrogation and reverse-transcriptase polymerase chain reaction (RT-PCR), we
      identified vertebrate orthologs of each of these LARGE genes in many vertebrates,
      including human, mouse, dog, chicken, zebrafish, and pufferfish. However, within
      invertebrate genomes, we were able to identify only single homologs. We suggest
      that vertebrate LARGE orthologs be referred to as LARGE1. RT-PCR, dot-blot, and
      northern analysis indicated that LARGE2 has a more restricted tissue-expression
      profile than LARGE1. Using epitope-tagged proteins, we show that both LARGE1 and
      LARGE2 localize to the Golgi apparatus. The high similarity between the LARGE
      paralogs suggests that LARGE2 may also act on DG. Overexpression of LARGE2 in
      mouse C2C12 myoblasts results in increased glycosylation of alpha-DG accompanied
      by an increase in laminin binding. Thus, there may be functional redundancy
      between LARGE1 and LARGE2. Consistent with this idea, we show that alpha-DG is
      still fully glycosylated in kidney (a tissue that expresses a high level of
      LARGE2 mRNA) of Large(myd) mutant mice.

PMID- 15958418
TI  - Development of structural analysis of sulfated N-glycans by multidimensional high
      performance liquid chromatography mapping methods.
AB  - Although the biological importance of sulfated oligosaccharides has been widely
      recognized, there are only a few reports that describe detailed structures of
      sulfated N-glycans. This is largely due to the lack of a convenient method to
      identify structures of sulfated glycans found in low incidence. Here we develop
      multidimensional high performance liquid chromatography (HPLC) mapping methods
      for rapid and convenient identification of sulfated N-glycans. By using adequate
      quantities of sulfated N-glycans derived from LS12 cells, which are transfected
      with sulfotransferase cDNA, 40 different sulfated glycans have been successfully
      mapped. Furthermore, we have applied the HPLC data to identification of isomeric
      products resulting from an enzymatic reaction of N-acetylglucosamine 6-O
      sulfotransferase-1 in vitro and revealed that this enzyme preferentially
      catalyzes sulfation of the GlcNAcbeta1-->2Manalpha1-->3Man branch in a
      biantennary acceptor.

PMID- 15958420
TI  - Editorial: unfortunate, but timely.

PMID- 15958419
TI  - Unusual sugar specificity of banana lectin from Musa paradisiaca and its probable
      evolutionary origin. Crystallographic and modelling studies.
AB  - The crystal structure of a complex of methyl-alpha-D-mannoside with banana lectin
      from Musa paradisiaca reveals two primary binding sites in the lectin, unlike in
      other lectins with beta-prism I fold which essentially consists of three Greek
      key motifs. It has been suggested that the fold evolved through successive gene
      duplication and fusion of an ancestral Greek key motif. In other lectins, all
      from dicots, the primary binding site exists on one of the three motifs in the
      three-fold symmetric molecule. Banana is a monocot, and the three motifs have not
      diverged enough to obliterate sequence similarity among them. Two Greek key
      motifs in it carry one primary binding site each. A common secondary binding site
      exists on the third Greek key. Modelling shows that both the primary sites can
      support 1-2, 1-3, and 1-6 linked mannosides with the second residue interacting
      in each case primarily with the secondary binding site. Modelling also readily
      leads to a bound branched mannopentose with the nonreducing ends of the two
      branches anchored at the two primary binding sites, providing a structural
      explanation for the lectin's specificity for branched alpha-mannans. A comparison
      of the dimeric banana lectin with other beta-prism I fold lectins, provides
      interesting insights into the variability in their quaternary structure.

PMID- 15958421
TI  - Disasters: introduction and state of the art.

PMID- 15958422
TI  - Methodological challenges and contributions in disaster epidemiology.

PMID- 15958423
TI  - The Lancet-Saturday 13 May 1972. 1972.

PMID- 15958424
TI  - Epidemiology of tropical cyclones: the dynamics of disaster, disease, and
      development.

PMID- 15958425
TI  - Global health impacts of floods: epidemiologic evidence.

PMID- 15958426
TI  - Epidemiology of traumatic injuries from earthquakes.

PMID- 15958427
TI  - The Chernobyl disaster: cancer following the accident at the Chernobyl nuclear
      power plant.

PMID- 15958428
TI  - Civil conflicts in four african countries: a five-year review of trends in
      nutrition and mortality.

PMID- 15958429
TI  - The epidemiology of post-traumatic stress disorder after disasters.

PMID- 15958430
TI  - Medically unexplained physical symptoms in the aftermath of disasters.

PMID- 15958431
TI  - The role of the media and media hypes in the aftermath of disasters.

PMID- 15958432
TI  - A stitch in time: improving public health early warning systems for extreme
      weather events.

PMID- 15958433
TI  - ST-segment elevation acute myocardial infarction: reperfusion at any cost?

PMID- 15958434
TI  - Plasma levels of B-type natriuretic peptide in children and adolescents with
      aortic valve stenosis.

PMID- 15958435
TI  - Mobilization of bone marrow-derived stem cells after myocardial infarction and
      left ventricular function: simply effects of optimized drug treatment?

PMID- 15958436
TI  - DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre
      trial of occluded artery angioplasty after acute myocardial infarction: DECOPI or
      NOT DECOPI: more smoke on the horizon.

PMID- 15958437
TI  - Recombinant human erythropoietin in oncology: current status and further
      developments.
AB  - Anaemia effects up to 90% of cancer patients, with more than 60% requiring blood
      transfusion during or after treatment. With the advent of recombinant human
      erythropoietins (rHuEPO), an alternative to red blood cell transfusion has become
      available. So far, three drugs have been approved for the treatment of anaemia in
      patients with malignancies (epoetin alfa, epoetin beta and darbepoetin alfa). New
      concepts for the use of erythropoietin in cancer patients include 3- and 4-weekly
      dosing, as well as loading-dose concepts. Important factors helping to judge the
      impact of erythropoietin in cancer treatment include pharmacoeconomics and better
      predictive factors. Lately, the influence of erythropoietin therapy on survival
      in cancer patients has been discussed very intensively, because conflicting data
      have emerged. Studies aimed at correcting anaemia in cancer patients had
      indicated a possible survival advantage of those patients receiving
      erythropoietin. In contrast, two recent trials aimed at correction of haemoglobin
      levels beyond anaemia reported a poorer survival of patients receiving
      erythropoietin. This might grossly be attributed to a higher risk of thrombosis
      in these patients. The largest systematic review on the use of erythropoietin in
      cancer patients undergoing treatment indicates a suggestive but not significant
      survival advantage of erythropoietin-treated patients. In addition, very recent
      results of a Food and Drug Administration meeting on safety and survival of
      patients treated with erythropoietin are presented.

PMID- 15958438
TI  - Advances in molecular biology diagnostic and treatment of B-cell malignancies.

PMID- 15958439
TI  - Advances in biology and treatment of multiple myeloma.

PMID- 15958440
TI  - Biology and treatment of chronic lymphocytic leukemia.

PMID- 15958442
TI  - Colorectal cancer: screening.

PMID- 15958444
TI  - (Neo-)adjuvant treatments in colorectal cancer.

PMID- 15958445
TI  - The handling of metastatic colorectal cancer.

PMID- 15958446
TI  - Treatment of liver metastases of colorectal cancer.

PMID- 15958448
TI  - Evaluation of service screening mammography in practice: the impact on breast
      cancer mortality.

PMID- 15958450
TI  - Genetic counselling in breast and colorectal cancer.

PMID- 15958452
TI  - Latest developments in local treatment: radiotherapy for early breast cancer.

PMID- 15958453
TI  - Neo-adjuvant therapy in breast cancer.

PMID- 15958455
TI  - New developments in the treatment of metastatic breast cancer: from chemotherapy
      to biological therapy.

PMID- 15958454
TI  - Adjuvant treatment for early breast cancer.

PMID- 15958456
TI  - Gene profile and response to treatment.

PMID- 15958457
TI  - An integrated approach for tailored treatment in breast cancer.

PMID- 15958460
TI  - Lung cancer screening: panacea or pipe dream?

PMID- 15958458
TI  - Breast cancer: communication with a breast cancer patient and a relative.

PMID- 15958461
TI  - The role of surgery in non-small-cell lung cancers.

PMID- 15958462
TI  - The role of radiotherapy in non-small-cell lung cancer.

PMID- 15958463
TI  - Medical treatment of non-small-cell lung cancer.

PMID- 15958464
TI  - Management of small-cell lung cancer.

PMID- 15958465
TI  - State of the art in mesothelioma.

PMID- 15958466
TI  - Head and neck cancer: molecular carcinogenesis.

PMID- 15958467
TI  - Surgical aspects in head and neck cancer.

PMID- 15958468
TI  - New trends in radiotherapy for head and neck cancer.

PMID- 15958469
TI  - Medical treatment in head and neck cancer.

PMID- 15958470
TI  - Head and neck cancer: treatment of nasopharyngeal cancer.

PMID- 15958471
TI  - Is cancer epidemiology different in Western Europe to that in Eastern Europe?

PMID- 15958472
TI  - Genomics and proteomics--the way forward.

PMID- 15958474
TI  - Application and safety of erythropoietin in cancer management.

PMID- 15958476
TI  - Immunotherapy of hematological malignancies: what is new?

PMID- 15958477
TI  - New imaging techniques in cancer management.

PMID- 15958479
TI  - ESMO Minimum Clinical Recommendations: assuring common standards of care.

PMID- 15958480
TI  - New techniques in irradiation: clinical implications of perioperative high-dose
      rate brachytherapy.

PMID- 15958481
TI  - How to deal with difficult pain problems.

PMID- 15958483
TI  - Colon cancer: laparoscopic resection.

PMID- 15958484
TI  - The role of chemotherapy in cholangiocarcinoma.

PMID- 15958485
TI  - Advances in molecular biology diagnostic and treatment of B-cell malignancies:
      indolent B-cell lymphoma.

PMID- 15958486
TI  - The cotranslational maturation of the type I membrane glycoprotein tyrosinase:
      the heat shock protein 70 system hands off to the lectin-based chaperone system.
AB  - The maturation of eukaryotic secretory cargo initiates cotranslationally and
      cotranslocationally as the polypeptide chain emerges into the endoplasmic
      reticulum lumen. Here, we characterized the cotranslational maturation pathway
      for the human type I membrane glycoprotein tyrosinase. To recapitulate the
      cotranslational events, including glycosylation, signal sequence cleavage,
      chaperone binding, and oxidation, abbreviated transcripts lacking a stop codon
      were in vitro translated in the presence of semipermeabilized melanocyte
      membranes. This created a series of ribosome/translocon-arrested chains of
      increasing lengths, simulating intermediates in the cotranslational folding
      process. Initially, nascent chains were found to associate with the heat shock
      protein (Hsp) 70 family member BiP. As the nascent chains elongated and
      additional glycans were transferred, BiP binding rapidly decreased and the lectin
      based chaperone system was recruited in its place. The lectin chaperone calnexin
      bound to the nascent chain after the addition of two glycans, and calreticulin
      association followed upon the addition of a third. The glycan-specific
      oxidoreductase ERp57 was cross-linked to tyrosinase when calnexin and
      calreticulin were associated. This timing coincided with the formation of
      disulfide bonds within tyrosinase and the cleavage of its signal sequence.
      Therefore, tyrosinase maturation initiates cotranslationally with the Hsp70
      system and is handed off to the lectin chaperone system that first uses calnexin
      before calreticulin. Interestingly, divergence in the maturation pathways of wild
      type and mutant albino tyrosinase can already be observed for translocon-arrested
      nascent chains.

PMID- 15958487
TI  - Targeting of Tsc13p to nucleus-vacuole junctions: a role for very-long-chain
      fatty acids in the biogenesis of microautophagic vesicles.
AB  - TSC13 is required for the biosynthesis of very-long-chain fatty acids (VLCFAs) in
      yeast. Tsc13p is a polytopic endoplasmic reticulum (ER) membrane protein that
      accumulates at nucleus-vacuole (NV) junctions, which are formed through Velcro
      like interactions between Nvj1p in the perinuclear ER and Vac8p on the vacuole
      membrane. NV junctions mediate piecemeal microautophagy of the nucleus (PMN),
      during which bleb-like portions of the nucleus are extruded into invaginations of
      the vacuole membrane and degraded in the vacuole lumen. We report that Tsc13p is
      sequestered into NV junctions from the peripheral ER through Vac8p-independent
      interactions with Nvj1p. During nutrient limitation, Tsc13p is incorporated into
      PMN vesicles in an Nvj1p-dependent manner. The lumenal diameters of PMN blebs and
      vesicles are significantly reduced in tsc13-1 and tsc13-1 elo3-Delta mutant
      cells. PMN structures are also smaller in cells treated with cerulenin, an
      inhibitor of de novo fatty acid synthesis and elongation. The targeting of Tsc13p
      GFP into NV junctions is perturbed by cerulenin, suggesting that its binding to
      Nvj1p depends on the availability of fatty acid substrates. These results
      indicate that Nvj1p retains and compartmentalizes Tsc13p at NV junctions and that
      VLCFAs contribute to the normal biogenesis of trilaminar PMN structures in yeast.

PMID- 15958488
TI  - Assembly of urothelial plaques: tetraspanin function in membrane protein
      trafficking.
AB  - The apical surface of mammalian urothelium is covered by 16-nm protein particles
      packed hexagonally to form 2D crystals of asymmetric unit membranes (AUM) that
      contribute to the remarkable permeability barrier function of the urinary
      bladder. We have shown previously that bovine AUMs contain four major integral
      membrane proteins, i.e., uroplakins Ia, Ib, II, and IIIa, and that UPIa and Ib
      (both tetraspanins) form heterodimers with UPII and IIIa, respectively. Using a
      panel of antibodies recognizing different conformational states of uroplakins, we
      demonstrate that the UPIa-dependent, furin-mediated cleavage of the prosequence
      of UPII leads to global conformational changes in mature UPII and that UPIb also
      induces conformational changes in its partner UPIIIa. We further demonstrate that
      tetraspanins CD9, CD81, and CD82 can stabilize their partner protein CD4. These
      results indicate that tetraspanin uroplakins, and some other tetraspanin
      proteins, can induce conformational changes leading to the ER-exit,
      stabilization, and cell surface expression of their associated, single
      transmembrane-domained partner proteins and thus can function as "maturation
      facilitators." We propose a model of AUM assembly in which conformational changes
      in integral membrane proteins induced by uroplakin interactions, differentiation
      dependent glycosylation, and the removal of the prosequence of UPII play roles in
      regulating the assembly of uroplakins to form AUM.

PMID- 15958489
TI  - Cell cycle-dependent dynamics and regulation of mitotic kinesins in Drosophila S2
      cells.
AB  - Constructing a mitotic spindle requires the coordinated actions of several
      kinesin motor proteins. Here, we have visualized the dynamics of five green
      fluorescent protein (GFP)-tagged mitotic kinesins (class 5, 6, 8, 13, and 14) in
      live Drosophila Schneider cell line (S2), after first demonstrating that the GFP
      tag does not interfere with the mitotic functions of these kinesins using an RNA
      interference (RNAi)-based rescue strategy. Class 8 (Klp67A) and class 14 (Ncd)
      kinesin are sequestered in an active form in the nucleus during interphase and
      engage their microtubule targets upon nuclear envelope breakdown (NEB).
      Relocalization of Klp67A to the cytoplasm using a nuclear export signal resulted
      in the disassembly of the interphase microtubule array, providing support for the
      hypothesis that this kinesin class possesses microtubule-destabilizing activity.
      The interactions of Kinesin-5 (Klp61F) and -6 (Pavarotti) with microtubules, on
      the other hand, are activated and inactivated by Cdc2 phosphorylation,
      respectively, as shown by examining localization after mutating Cdc2 consensus
      sites. The actions of microtubule-destabilizing kinesins (class 8 and 13
      [Klp10A]) seem to be controlled by cell cycle-dependent changes in their
      localizations. Klp10A, concentrated on microtubule plus ends in interphase and
      prophase, relocalizes to centromeres and spindle poles upon NEB and remains at
      these sites throughout anaphase. Consistent with this localization, RNAi analysis
      showed that this kinesin contributes to chromosome-to-pole movement during
      anaphase A. Klp67A also becomes kinetochore associated upon NEB, but the majority
      of the population relocalizes to the central spindle by the timing of anaphase A
      onset, consistent with our RNAi result showing no effect of depleting this motor
      on anaphase A. These results reveal a diverse spectrum of regulatory mechanisms
      for controlling the localization and function of five mitotic kinesins at
      different stages of the cell cycle.

PMID- 15958490
TI  - Structure-based functional analysis reveals a role for the SM protein Sly1p in
      retrograde transport to the endoplasmic reticulum.
AB  - Sec1p/Munc18 (SM) proteins are essential for membrane fusion events in eukaryotic
      cells. Here we describe a systematic, structure-based mutational analysis of the
      yeast SM protein Sly1p, which was previously shown to function in anterograde
      endoplasmic reticulum (ER)-to-Golgi and intra-Golgi protein transport. Five new
      temperature-sensitive (ts) mutants, each carrying a single amino acid
      substitution in Sly1p, were identified. Unexpectedly, not all of the ts mutants
      exhibited striking anterograde ER-to-Golgi transport defects. For example, in
      cells of the novel sly1-5 mutant, transport of newly synthesized lysosomal and
      secreted proteins was still efficient, but the ER-resident Kar2p/BiP was
      missorted to the outside of the cell, and two proteins, Sed5p and Rer1p, which
      normally shuttle between the Golgi and the ER, failed to relocate to the ER. We
      also discovered that in vivo, Sly1p was associated with a SNARE complex formed on
      the ER, and that in vitro, the SM protein directly interacted with the ER
      localized nonsyntaxin SNAREs Use1p/Slt1p and Sec20p. Furthermore, several
      conditional mutants defective in Golgi-to-ER transport were synthetically lethal
      with sly1-5. Together, these results indicate a previously unrecognized function
      of Sly1p in retrograde transport to the endoplasmic reticulum.

PMID- 15958491
TI  - Inositol 1,4,5-trisphosphate signaling regulates mating behavior in
      Caenorhabditis elegans males.
AB  - Complex behavior requires the coordinated action of the nervous system and
      nonneuronal targets. Male mating in Caenorhabditis elegans consists of a series
      of defined behavioral steps that lead to the physiological outcomes required for
      successful impregnation. We demonstrate that signaling mediated by inositol 1,4,5
      trisphosphate (IP(3)) is required at several points during mating. Disruption of
      IP(3) receptor (itr-1) function results in dramatic loss of male fertility, due
      to defects in turning behavior (during vulva location), spicule insertion and
      sperm transfer. To elucidate the signaling pathways responsible, we knocked down
      the six C. elegans genes encoding phospholipase C (PLC) family members. egl-8,
      which encodes PLC-beta, functions in spicule insertion and sperm transfer. itr-1
      and egl-8 are widely expressed in the male reproductive system. An itr-1 gain-of
      function mutation rescues infertility caused by egl-8 RNA interference,
      indicating that egl-8 and itr-1 function together as central components of the
      signaling events controlling sperm transfer.

PMID- 15958492
TI  - Dsl1p, Tip20p, and the novel Dsl3(Sec39) protein are required for the stability
      of the Q/t-SNARE complex at the endoplasmic reticulum in yeast.
AB  - The "Dsl1p complex" in Saccharomyces cerevisiae, consisting of Dsl1p and Tip20p,
      is involved in Golgi-ER retrograde transport and it is functionally conserved
      from yeast to mammalian cells. To further characterize this complex, we analyzed
      the function of Dsl3p, a protein that interacts with Dsl1p in yeast two hybrids
      screens. DSL3, recently identified in a genome wide analysis of essential genes
      as SEC39, encodes a cytosolic protein of 82 kDa that is peripherally associated
      with membranes derived from the ER. There is strong genetic interaction between
      DSL3 and other factors required for Golgi-ER retrograde transport. Size exclusion
      chromatography and affinity purification approaches confirmed that Dsl3p is
      associated with subunits of the "Dsl1p complex." The complex also includes the
      Q/t-SNARE proteins, Use1p, Sec20p, and Ufe1p, integral membrane proteins that
      constitute the trimeric acceptor for R/v-SNAREs on Golgi-derived vesicles at the
      ER. Using mutants, we performed a detailed analysis of interactions between
      subunits of the Dsl1p complex and the ER-localized SNARE proteins. This analysis
      showed that both Dsl1p and Dsl3p are required for the stable interaction of the
      SNARE Use1p with a central subcomplex consisting of Tip20p and the SNARE proteins
      Ufe1p and Sec20p.

PMID- 15958493
TI  - Genetic, genomic, and functional analysis of the granule lattice proteins in
      Tetrahymena secretory granules.
AB  - In some cells, the polypeptides stored in dense core secretory granules condense
      as ordered arrays. In ciliates such as Tetrahymena thermophila, the resulting
      crystals function as projectiles, expanding upon exocytosis. Isolation of granule
      contents previously defined five Granule lattice (Grl) proteins as abundant core
      constituents, whereas a functional screen identified a sixth family member. We
      have now expanded this screen to identify the nonredundant components required
      for projectile assembly. The results, further supported by gene disruption
      experiments, indicate that six Grl proteins define the core structure. Both in
      vivo and in vitro data indicate that core assembly begins in the endoplasmic
      reticulum with formation of specific hetero-oligomeric Grl proprotein complexes.
      Four additional GRL-like genes were found in the T. thermophila genome. Grl2p and
      Grl6p are targeted to granules, but the transcripts are present at low levels and
      neither is essential for core assembly. The DeltaGRL6 cells nonetheless showed a
      subtle change in granule morphology and a marked reduction in granule
      accumulation. Epistasis analysis suggests this results from accelerated loss of
      DeltaGRL6 granules, rather than from decreased synthesis. Our results not only
      provide insight into the organization of Grl-based granule cores but also imply
      that the functions of Grl proteins extend beyond core assembly.

PMID- 15958494
TI  - Actin depolymerization disrupts tight junctions via caveolae-mediated
      endocytosis.
AB  - The tight junction (TJ) determines epithelial barrier function. Actin
      depolymerization disrupts TJ structure and barrier function, but the mechanisms
      of this effect remain poorly understood. The goal of this study was to define
      these mechanisms. Madin-Darby canine kidney (MDCK) cells expressing enhanced
      green fluorescent protein-, enhanced yellow fluorescent protein-, or monomeric
      red fluorescent protein 1-fusion proteins of beta-actin, occludin, claudin-1, ZO
      1, clathrin light chain A1, and caveolin-1 were imaged by time-lapse
      multidimensional fluorescence microscopy with simultaneous measurement of
      transepithelial electrical resistance (TER). Actin depolymerization was induced
      with latrunculin A (LatA). Within minutes of LatA addition TER began to fall.
      This coincided with occludin redistribution and internalization. In contrast, ZO
      1 and claudin-1 redistribution occurred well after maximal TER loss. Occludin
      internalization and TER loss, but not actin depolymerization, were blocked at 14
      degrees C, suggesting that membrane traffic is required for both events.
      Inhibition of membrane traffic with 0.4 M sucrose also blocked occludin
      internalization and TER loss. Internalized occludin colocalized with caveolin-1
      and dynamin II, but not with clathrin, and internalization was blocked by
      dominant negative dynamin II (K44A), but not by Eps15Delta95-295 expression.
      Inhibition of caveolae-mediated endocytosis by cholesterol extraction prevented
      both LatA-induced TER loss and occludin internalization. Thus, LatA-induced actin
      depolymerization causes TJ structural and functional disruption by mechanisms
      that include caveolae-mediated endocytosis of TJ components.

PMID- 15958495
TI  - Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for
      proper sister-chromatid cohesion.
AB  - Genetic studies in yeast and Drosophila have uncovered a conserved
      acetyltransferase involved in sister-chromatid cohesion. Here, we described the
      two human orthologues, previously named EFO1/ESCO1 and EFO2/ESCO2. Similar to
      their yeast (Eco1/Ctf7 and Eso1) and fly (deco) counterparts, both proteins
      feature a conserved C-terminal domain consisting of a H2C2 zinc finger motif and
      an acetyltransferase domain that is able to catalyze autoacetylation reaction in
      vitro. However, no similarity can be detected outside of the conserved domain.
      RNA interference depletion experiment revealed that EFO1/ESCO1 and EFO2/ESCO2
      were not redundant and that both were required for proper sister-chromatid
      cohesion. The difference between EFO1 and EFO2 also is reflected in their cell
      cycle regulation. In mitosis, EFO1 is phosphorylated, whereas EFO2 is degraded.
      Furthermore, both proteins associate with chromosomes, and the chromosome binding
      depends on the diverse N-terminal domains. We propose that EFO1 and EFO2 are
      targeted to different chromosome structures to help establish or maintain sister
      chromatid cohesion.

PMID- 15958496
TI  - Cloning and regulation of a stress-regulated Pennisetum glaucum vacuolar ATPase c
      gene and characterization of its promoter that is expressed in shoot hairs and
      floral organs.
AB  - We have cloned and characterized the cDNA, genomic clone and upstream promoter
      region of a vacuolar ATPase (V-ATPase) c subunit (PgVHA-c1) from Pennisetum
      glaucum. The deduced amino acid sequence shows 98-71% sequence identity with V
      ATPase from rice and Arabidopsis, and is a highly hydrophobic protein with four
      transmembrane regions. PgVHA-c1-GFP fusion protein is expressed in BY2 cells on
      the endo-membranes surrounding vacuoles; however, PgVHA-c1 could not functionally
      complement V-ATPase-c deletion mutants of yeast. The sequence analysis of the
      genomic clone revealed the presence of two introns in the coding region, and the
      splice junctions followed the typical canonical GU-AG consensus sequence. The
      transcript analysis showed that the expression of PgVHA-c1 was stimulated more in
      response to salinity stress and very marginally in response to drought and low
      temperature stress. Exogenous application of abscisic acid, salicylic acid and
      calcium stimulated the transcript level in the absence of stress. We have cloned
      the 5'-flanking regions of PgVHA-c1 and mapped its transcript start site at 78 bp
      upstream of ATG. Transgenic tobacco with promoter::GUS constructs showed that the
      region -288/+78 was sufficient for GUS expression. The expression of the reporter
      gene even with the full-length promoter was limited to shoot hairs and to male
      and female reproductive organs. The dehydration-responsive element (DRE) and ABA
      responsive element (ABRE) in the promoter did not show consensus flanking
      regions; however, gel mobility shift assays showed that Pennisetum has specific
      transacting factors that showed binding to the core DRE, ABRE and TCA elements.

PMID- 15958497
TI  - Brassinosteroid regulates fiber development on cultured cotton ovules.
AB  - Our current understanding of the role of phytohormones in the development of
      cotton fibers is derived largely from an amenable culture system in which cotton
      ovules, collected on the day of anthesis, are floated on liquid media. Under
      these conditions, supplemental auxin and gibberellin were found to promote fiber
      initiation and elongation. More recently, addition of low concentrations of the
      brassinosteroid brassinolide (BL) were also found to promote fiber elongation
      while a brassinosteroid biosynthesis inhibitor brassinazole2001 (Brz) inhibited
      fiber development. In order to elucidate the role of brassinosteroid in cotton
      fiber development further, we have performed a more detailed analysis of the
      effects of these chemicals on cultured cotton ovules. Our results confirm that
      exogenous BL promotes fiber elongation while treatment with Brz inhibits it.
      Furthermore, treatment of cotton floral buds with Brz results in the complete
      absence of fiber differentiation, indicating that BR is required for fiber
      initiation as well as elongation. Expression of fiber genes associated with cell
      elongation increased in ovules treated with BL and was suppressed by Brz
      treatment, establishing a correlation between brassinosteroid-regulated gene
      expression and fiber elongation. These results establish a clear connection
      between brassinosteroid and fiber development and open the door for genetic
      analysis of cotton development through direct modification of the brassinosteroid
      signal transduction pathway.

PMID- 15958498
TI  - Biological consequences of petite mutations in Candida glabrata.
AB  - OBJECTIVES: To define the pathogenicity of respiration-deficient mutants of
      Candida glabrata, which present a reduced susceptibility to azoles, that are
      easily induced in vitro by exposure to these drugs or to ethidium bromide and
      that may be selected in vivo in patients receiving fluconazole. METHODS: Two wild
      type isolates of C. glabrata were compared with their respective fluconazole- or
      ethidium bromide-induced petite mutants, regarding the carbohydrate and protein
      composition of the cell wall, as well as their surface physical properties, and
      also their adherence abilities and virulence in mice. RESULTS: Flow cytometric
      analysis of cell wall carbohydrates using several fluorescent lectins showed an
      increased binding of mutant cells to concanavalin A compared with their parent
      isolates, suggesting a greater availability or an increased amount of glucose
      mannose residues at the cell surface in petite mutants. Likewise, some
      quantitative differences between parent and mutant isolates were shown by SDS
      PAGE in protein extracts from blastoconidia. Regarding the surface physical
      properties, no significant differences were seen in the electrophoretic mobility
      determined by microelectrophoresis, but the two-phase partitioning method
      revealed a lower cell surface hydrophobicity for petite mutants. Moreover, mutant
      cells exhibited significant overexpression of CgEPA1 as revealed by real-time
      reverse transcription-PCR, but the adherence capacities to Caco-2 cells, a human
      enterocyte line, were not significantly different. Finally, in agreement with
      their slower growth, petite mutants were less virulent than parent isolates in a
      murine model of systemic infection. CONCLUSION: This low virulence in mice
      suggests that petite mutants could be disregarded clinically although they may
      arise during fluconazole therapy.

PMID- 15958499
TI  - Real-time PCR detection and frequency of 16S rDNA mutations associated with
      resistance and reduced susceptibility to tetracycline in Helicobacter pylori from
      England and Wales.
AB  - OBJECTIVES: To investigate the occurrence of 16S rDNA mutations associated with
      resistance or reduced susceptibility to tetracycline in Helicobacter pylori
      isolated in England and Wales, and to develop a real-time PCR assay to detect
      these DNA polymorphisms from culture and gastric biopsies. METHODS: Tetracycline
      susceptibility was determined by disc diffusion. The MIC of isolates with reduced
      susceptibility was determined by Etest and agar dilution methods. The 16S rDNA of
      these isolates was sequenced and resistance-associated mutations identified. A
      LightCycler assay developed to detect these mutations was applied to DNA
      extracted from culture and gastric biopsies. RESULTS: From 1006 isolates of H.
      pylori examined, 18 showed reduced susceptibility to tetracycline. Of these,
      three were resistant (>or=4 mg/L). Mutations in 16S rDNA were detected in 10 of
      the reduced susceptibility isolates: one double base mutation of A926T/A928C, one
      A926C, one A928C; and seven A926G. The first two polymorphisms were novel and had
      not been reported from clinical isolates previously. The LightCycler assay
      identified each of the 10 isolates with 16S rDNA mutations, but did not detect
      polymorphisms in 100 tetracycline-susceptible H. pylori isolates. The assay
      correctly determined the tetracycline susceptibility of H. pylori in 20 gastric
      biopsy samples. CONCLUSIONS: Mutations in 16S rDNA were detected in H. pylori
      isolated in England and Wales with reduced susceptibility to tetracycline, but
      resistance to this antibiotic was uncommon. We show molecular-based
      susceptibility testing for tetracycline is possible direct from biopsy material.

PMID- 15958500
TI  - The Pro279Leu variant in the transcription factor MEF2A is associated with
      myocardial infarction.
AB  - BACKGROUND: A myocyte enhancer factor 2A (MEF2A) mutation that segregated with
      coronary artery disease/myocardial infarction (CAD/MI) in a large family has
      recently been described. Missense mutations in sporadic coronary artery disease
      patients were also reported. These data suggest that mutations in exons 7 and 11
      of MEF2A cause CAD/MI, though the association was refuted by another study.
      OBJECTIVE: To analyse the genetic variation of exons 7 and 11 in a large cohort
      of Spanish CAD/MI patients and controls. METHODS AND RESULTS: A rare
      polymorphism, P279L, was detected both in patients and controls. Carriers of the
      279Leu allele had a threefold risk of suffering CAD/MI compared with controls (p
      = 0.009; odds ratio = 3.06 (95% confidence interval, 1.17 to 8.06)). In the
      controls the allele was found only in those under 50 years of age. Exon 11 showed
      a high degree of heterogeneity caused by a polyglutamine (CAG)n polymorphism, but
      no significant differences in genotype or allelic frequencies were found.
      CONCLUSIONS: The 279Leu allele appears to be a genetic risk factor for CAD/MI in
      the population studied. This effect could be the result of a reduced
      transcriptional activity on MEF2A with 279Leu.

PMID- 15958501
TI  - A novel locus for autosomal dominant non-syndromic deafness, DFNA53, maps to
      chromosome 14q11.2-q12.
AB  - BACKGROUND: Non-syndromic hearing loss is among the most genetically
      heterogeneous traits known in humans. To date, at least 50 loci for autosomal
      dominant non-syndromic sensorineural hearing loss (ADNSSHL) have been identified
      by linkage analysis. OBJECTIVE: To report the mapping of a novel autosomal
      dominant deafness locus on the long arm of chromosome 14 at 14q11.2-q12, DFNA53,
      in a large multigenerational Chinese family with post-lingual, high frequency
      hearing loss that progresses to involve all frequencies. RESULTS: A maximum
      multipoint LOD score of 5.4 was obtained for marker D14S1280. The analysis of
      recombinant haplotypes mapped DFNA53 to a 9.6 cM region interval between markers
      D14S581 and D14S1021. Four deafness loci (DFNA9, DFNA23, DFNB5, and DFNB35) have
      previously been mapped to the long arm of chromosome 14. The critical region for
      DFNA53 contains the gene for DFNA9 but does not overlap with the regions for
      DFNB5, DFNA23, or DFNB35. Screening of the COCH gene (DFNA9), BOCT, EFS, and
      HSPC156 within the DFNA53 interval did not identify the cause for deafness in
      this family. CONCLUSIONS: Identifying the DFNA53 locus is the first step in
      isolating the gene responsible for hearing loss in this large multigeneration
      Chinese family.

PMID- 15958503
TI  - MRI in the diagnosis of sporadic Creutzfeldt-Jakob disease: a study on inter
      observer agreement.
AB  - According to the current WHO criteria, technical investigations included in the
      clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) are
      electroencephalogram (EEG) and CSF-analysis for 14-3-3 proteins. MRI is not a
      criterion for the diagnosis of sCJD, although typical changes have been
      described. We investigated the reliability of MRI in the sCJD diagnosis,
      evaluated MRI sequences and compared MRI with EEG and 14-3-3. This study includes
      193 consecutive suspected sCJD patients who had been referred to the German CJD
      Surveillance Unit from 2001 to 2003. Three observers independently analysed MRI
      scans, blinded to clinical data. MRI was rated as 'typical for sCJD' if increased
      signal intensity was detected in the caudate nucleus and putamen. We analysed 442
      MRI scans [184 T2-weighted sequences, 132 fluid attenuated inversion recovery
      (FLAIR) sequences, 75 diffusion-weighted sequences and 51 proton-density weighted
      sequences]. Inter-observer agreement was 123 of 193 patients or 63.7% (overall
      kappa = 0.53). Sensitivity of MRI in clinically probable or autopsy-proven sCJD
      was 59.7% for Observer 1, 58.3% for Observer 2 and 70.8% for Observer 3;
      specificity was high (84.2, 89.5 and 81.6%, respectively). Diffusion-weighted
      sequences best showed the pathologic changes, followed by FLAIR. Periodic sharp
      and slow wave complexes were detected in the EEG in 32% (sensitivity), the 14-3-3
      proteins in CSF were elevated in 91%. We conclude that the detection of
      hyperintense basal ganglia in MRI helps to improve the clinical diagnosis, and
      therefore, we propose to incorporate MRI in the diagnostic criteria for sCJD.

PMID- 15958504
TI  - Multipotent progenitor cells from the adult human brain: neurophysiological
      differentiation to mature neurons.
AB  - It was long held as an axiom that new neurons are not produced in the adult human
      brain. More recent studies have identified multipotent cells whose progeny
      express glial or neuronal markers. This discovery may lead to new therapeutic
      strategies for CNS disorders, either by stimulating neurogenesis in vivo or by
      transplanting multipotent progenitor cells (MPCs) that have been propagated and
      differentiated in vitro. The clinical application of such approaches will be
      limited by the ability of these cells to develop into functional neurons. To
      facilitate an understanding of mechanisms regulating neurogenesis in the adult
      human brain, we characterized the developmental processes MPCs go through when
      progressing to a neuron. Human tissue was harvested during temporal lobe
      resections because of epilepsy, and cells were cultured as neurospheres. Our
      findings demonstrate that at an early stage, these cells often stain with
      neuronal markers without possessing any functional neuronal properties. Over a
      period of 4 weeks in culture, cells go through characteristic steps of
      morphological and electrophysiological development towards functional neurons;
      they develop a polarized appearance with multiple dendrites, whereas the membrane
      potential becomes more negative and the input resistance decreases [from -48 +/-
      10 mV/557 +/- 85 MOmega (n = 15) between days 7 and 11 to -59 +/- 9 mV/380 +/- 79
      MOmega (n = 9) between days 25 and 38, respectively]. Active membrane properties
      were first observed on day 7 and consisted of a voltage-gated K+-current. Later
      in the second week the cells developed voltage-gated Ca2+-channels and fired
      small Ca2+-driven action potentials. Immature Na+-driven action potentials
      developed from the beginning of the third week, and by the end of the fourth week
      the cells fired repetitive action potentials with a completely mature waveform
      generated by the combined action of the voltage-gated ionic channels INa, IA and
      IK. After 4 weeks, the newly formed neurons also communicated by the use of
      GABAergic and glutamatergic synapses. The adult human brain thus harbours MPCs,
      which have the ability to develop into neurons and in doing this follow
      characteristic steps of neurogenesis as seen in the developing brain.

PMID- 15958502
TI  - The lentiginoses: cutaneous markers of systemic disease and a window to new
      aspects of tumourigenesis.
AB  - Familial lentiginosis syndromes cover a wide phenotypic spectrum ranging from a
      benign inherited predisposition to develop cutaneous lentigines unassociated with
      systemic disease, to associations with several syndromes carrying increased risk
      of formation of hamartomas, hyperplasias, and other neoplasms. The molecular
      pathways involved in the aetiology of these syndromes have recently been more
      clearly defined and several major cellular signalling pathways are probably
      involved: the protein kinase A (PKA) pathway in Carney complex (CNC), the Ras/Erk
      MAP kinase pathway in LEOPARD/Noonan syndromes, and the mammalian target of
      rapamycin pathway (mTOR) in Peutz-Jeghers syndrome and the diseases caused by
      PTEN mutations. Here we discuss the clinical presentation of these disorders and
      discuss the molecular mechanisms involved. The presence of lentigines in these
      diseases caused by diverse molecular defects is probably more than an associated
      clinical feature and likely reflects cross talk and convergence of signalling
      pathways of central importance to embryogenesis, neural crest differentiation,
      and end-organ growth and function of a broad range of tissues including those of
      the endocrine, reproductive, gastrointestinal, cardiac, and integument systems.

PMID- 15958505
TI  - A functional MRI study of automatic movements in patients with Parkinson's
      disease.
AB  - Patients with Parkinson's disease have great difficulty performing learned
      movements automatically. The neural contribution to the problem has not been
      identified. In the current study, we used functional magnetic resonance imaging
      (fMRI) to investigate the underlying neural mechanisms of movement automaticity
      in Parkinson's disease patients. Fifteen patients with Parkinson's disease were
      recruited. Three patients were finally excluded because they could not achieve
      automaticity. The remaining 12 patients were aged from 52 to 67 years, with a
      mean age of 61.2 years. Controls included 14 age-matched normal subjects. The
      subjects were asked to practise four tasks, including two self-initiated, self
      paced sequences of finger movements with different complexity until they could
      perform the tasks automatically. Two dual tasks were used to evaluate
      automaticity. For dual tasks, subjects performed a visual letter-counting task
      simultaneously with the sequential movements. Twelve normal subjects performed
      all sequences automatically. All patients performed sequences correctly; 12
      patients could perform the simpler sequence automatically; and only 3 patients
      could perform the more complex sequence automatically. fMRI results showed that
      for both groups, sequential movements activated similar brain regions before and
      after automaticity was achieved. No additional activity was observed in the
      automatic condition. In normal subjects, many areas had reduced activity at the
      automatic stage, whereas in patients, only the bilateral superior parietal lobes
      and left insular cortex were less activated. Patients had greater activity in the
      cerebellum, premotor area, parietal cortex, precuneus and prefrontal cortex
      compared with normal subjects while performing automatic movements. We conclude
      that Parkinson's disease patients can achieve automaticity after proper training,
      but with more difficulty. Our study is the first to demonstrate that patients
      with Parkinson's disease require more brain activity to compensate for basal
      ganglia dysfunction in order to perform automatic movements.

PMID- 15958506
TI  - Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from
      chronic epileptic rats and humans.
AB  - Metabolic dysfunction has been implicated in the pathogenesis of temporal lobe
      epilepsy (TLE), but its manifestation during neuronal activation in the ex vivo
      hippocampus from TLE patients has not been shown. We characterized metabolic and
      mitochondrial functions in acute hippocampal slices from pilocarpine-treated,
      chronic epileptic rats and from pharmaco-resistant TLE patients. Recordings of
      NAD(P)H fluorescence indicated the status of cellular energy metabolism, and
      simultaneous monitoring of extracellular potassium concentration ([K+]o) allowed
      us to control the induction of neuronal activation. In control rats, electrical
      stimulation elicited biphasic NAD(P)H fluorescence transients that were
      characterized by a brief initial 'drop' and a subsequent prolonged 'overshoot'
      correlating to enhanced NAD(P)+ reduction. In chronic epileptic rats, overshoots
      were significantly smaller in area CA1, but not in the subiculum as compared to
      controls. In TLE patients, who were histopathologically classified in groups with
      and without Ammon's horn sclerosis (AHS, non-AHS), large drops and very small
      overshoots of NAD(P)H transients were observed in dentate gyrus, CA3, CA1 and
      subiculum. Nevertheless, monitoring mitochondrial membrane potential
      (DeltaPsi(m)) by mitochondria-specific, voltage-sensitive dye (rhodamine-123)
      revealed similar mitochondrial responses during neuronal activation with
      glutamate and protonophore application in area CA1 of control and chronic
      epileptic rats. Applying confocal laser scanning microscopy, these findings were
      confirmed in individual neurons of AHS tissue, indicating a negative DeltaPsi(m)
      and activation-dependent mitochondrial depolarization. Our data demonstrate
      severe metabolic dysfunction during neuronal activation in the hippocampus from
      chronic epileptic rats and humans, although mitochondria maintain negative
      DeltaPsi(m). Thus, our findings provide a cellular correlate for 'hypometabolism'
      as described for epilepsy patients and suggest mitochondrial enzyme defects in
      TLE.

PMID- 15958507
TI  - MTI of white matter hyperintensities.
AB  - The severity of tissue changes associated with incidental white matter
      hyperintensities (WMH) in the elderly cannot be sufficiently determined by
      conventional MRI. We, therefore, performed a regional analysis of the
      magnetization transfer ratio (MTR) maps obtained on a 1.5 T scanner from 198
      neurologically asymptomatic participants of the Austrian Stroke Prevention Study
      (mean age 70, age range 52-87 years) in regard to WMH and predefined areas of
      normal appearing brain tissue. Fluid attenuated inversion recovery MRI was used
      to grade lesion severity and for lesion volume measurements. The MTR of WMH was
      always significantly lower than that of normal appearing white matter (NAWM) with
      an overall relative reduction of approximately 10% and decreased significantly
      with increasing scores of WMH severity (P = 0.02) and WMH volume (r = -0.24, P =
      0.0016). NAWM MTR was not different between subjects with very few and extensive
      WMH and the WMH volume was associated with NAWM MTR of the frontal lobes only.
      Concerning a possible impact on cerebral functioning the MTR of the frontal NAWM
      was significantly associated with fine motor dexterity (P = 0.04) but not with
      cognitive performance. A significant decline of the MTR with aging was seen in
      both NAWM and cortex but not in WMH. We conclude that MTR measurements can serve
      to quantify WMH associated tissue damage. It is predominantly focal, relatively
      mild, increases with lesion size and may have remote effects on the frontal white
      matter.

PMID- 15958508
TI  - Enhanced and diminished visuo-spatial information processing in autism depends on
      stimulus complexity.
AB  - Visuo-perceptual processing in autism is characterized by intact or enhanced
      performance on static spatial tasks and inferior performance on dynamic tasks,
      suggesting a deficit of dorsal visual stream processing in autism. However,
      previous findings by Bertone et al. indicate that neuro-integrative mechanisms
      used to detect complex motion, rather than motion perception per se, may be
      impaired in autism. We present here the first demonstration of concurrent
      enhanced and decreased performance in autism on the same visuo-spatial static
      task, wherein the only factor dichotomizing performance was the neural complexity
      required to discriminate grating orientation. The ability of persons with autism
      was found to be superior for identifying the orientation of simple, luminance
      defined (or first-order) gratings but inferior for complex, texture-defined (or
      second-order) gratings. Using a flicker contrast sensitivity task, we
      demonstrated that this finding is probably not due to abnormal information
      processing at a sub-cortical level (magnocellular and parvocellular functioning).
      Together, these findings are interpreted as a clear indication of altered low
      level perceptual information processing in autism, and confirm that the deficits
      and assets observed in autistic visual perception are contingent on the
      complexity of the neural network required to process a given type of visual
      stimulus. We suggest that atypical neural connectivity, resulting in enhanced
      lateral inhibition, may account for both enhanced and decreased low-level
      information processing in autism.

PMID- 15958509
TI  - Gain-of-function mutation in Nav1.7 in familial erythromelalgia induces bursting
      of sensory neurons.
AB  - Erythromelalgia is an autosomal dominant disorder characterized by burning pain
      in response to warm stimuli or moderate exercise. We describe a novel mutation in
      a family with erythromelalgia in SCN9A, the gene that encodes the Na(v)1.7 sodium
      channel. Na(v)1.7 produces threshold currents and is selectively expressed within
      sensory neurons including nociceptors. We demonstrate that this mutation, which
      produces a hyperpolarizing shift in activation and a depolarizing shift in steady
      state inactivation, lowers thresholds for single action potentials and high
      frequency firing in dorsal root ganglion neurons. Erythromelalgia is the first
      inherited pain disorder in which it is possible to link a mutation with an
      abnormality in ion channel function and with altered firing of pain signalling
      neurons.

PMID- 15958510
TI  - Essential kinase-independent role of a Fer-like non-receptor tyrosine kinase in
      Caenorhabditis elegans morphogenesis.
AB  - Morphogenesis requires coordination of cell surface activity and cytoskeletal
      architecture. During the initial stage of morphogenesis in Caenorhabditis
      elegans, the concerted movement of surface epithelial cells results in enclosure
      of the embryo by the epidermis. We report that Fer-related kinase-1 (FRK-1), an
      ortholog of the mammalian non-receptor tyrosine kinase Fer, is necessary for
      embryonic enclosure and morphogenesis in C. elegans. Expression of FRK-1 in
      epidermal cells is sufficient to rescue a chromosomal deficiency that removes the
      frk-1 locus, demonstrating its autonomous requirement in the epidermis. The
      essential function of FRK-1 is independent of its kinase domain, suggesting a non
      enzymatic role in morphogenesis. Localization of FRK-1 to the plasma membrane
      requires beta-catenin, but not cadherin or alpha-catenin, and muscle-expressed
      beta-integrin is non-autonomously required for this localization; in the absence
      of these components FRK-1 becomes nuclear. Mouse FerT rescues the morphogenetic
      defects of frk-1 mutants and expression of FRK-1 in mammalian cells results in
      loss of adhesion, implying a conserved function for FRK-1/FerT in cell adhesion
      and morphogenesis. Thus, FRK-1 performs a kinase-independent function in
      differentiation and morphogenesis of the C. elegans epidermis during
      embryogenesis.

PMID- 15958511
TI  - SMAD pathway mediation of BDNF and TGF beta 2 regulation of proliferation and
      differentiation of hippocampal granule neurons.
AB  - Hippocampal granule cells self-renew throughout life, whereas their cerebellar
      counterparts become post-mitotic during early postnatal development, suggesting
      that locally acting, tissue-specific factors may regulate the proliferative
      potential of each cell type. Confirming this, we show that conditioned medium
      from hippocampal cells (CM(Hippocampus)) stimulates proliferation in cerebellar
      cultures and, vice versa, that mitosis in hippocampal cells is inhibited by
      CM(Cerebellum). The anti-proliferative effects of CM(Cerebellum) were accompanied
      by increased expression of the cyclin-dependent kinase inhibitors p21 and p27, as
      well as markers of neuronal maturity/differentiation. CM(Cerebellum) was found to
      contain peptide-like factors with distinct anti-proliferative/differentiating and
      neuroprotective activities with differing chromatographic properties.
      Preadsorption of CM(Cerebellum) with antisera against candidate cytokines showed
      that TGFbeta2 and BDNF could account for the major part of the anti-proliferative
      and pro-differentiating activities, an interpretation strengthened by studies
      involving treatment with purified TGFbeta2 and BDNF. Interference with signaling
      pathways downstream of TGFbeta and BDNF using dominant-negative forms of their
      respective receptors (TGFbeta2-RII and TRKB) or of dominant-negative forms of
      SMAD3 and co-SMAD4 negated the anti-proliferative/differentiating actions of
      CM(Cerebellum). Treatment with CM(Cerebellum) caused nuclear translocation of
      SMAD2 and SMAD4, and also transactivated a TGFbeta2-responsive gene. BDNF actions
      were shown to depend on activation of ERK1/2 and to converge on the SMAD
      signaling cascade, possibly after stimulation of TGFbeta2 synthesis/secretion. In
      conclusion, our results show that the regulation of hippocampal cell fate in
      vitro is regulated through an interplay between the actions of BDNF and TGFbeta.

PMID- 15958512
TI  - A dual role of FGF10 in proliferation and coordinated migration of epithelial
      leading edge cells during mouse eyelid development.
AB  - The development of the eyelid requires coordinated cellular processes of
      proliferation, cell shape changes, migration and cell death. Mutant mice
      deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit open-eyelids at
      birth. To elucidate the roles of FGF10 during eyelid formation, we examined the
      expression pattern of Fgf10 during eyelid formation and the phenotype of Fgf10
      null eyelids in detail. Fgf10 is expressed by mesenchymal cells just beneath the
      protruding epidermal cells of the nascent eyelid. However, Fgf10-null epithelial
      cells running though the eyelid groove do not exhibit typical cuboid shape or
      sufficient proliferation. Furthermore, peridermal clumps are not maintained on
      the eyelid leading edge, and epithelial extension does not occur. At the cellular
      level, the accumulation of actin fibers is not observed in the mutant epithelial
      leading edge. The expression of activin/inhibin betaB (ActbetaB/Inhbb) and
      transforming growth factor alpha (Tgfa), previously reported to be crucial for
      eyelid development, is down-regulated in the mutant leading edge, while the onset
      of sonic hedgehog (Shh) expression is delayed on the mutant eyelid margin.
      Explant cultures of mouse eyelid primordia shows that the open-eyelid phenotype
      of the mutant is reduced by exogenous FGF10 protein, and that the expression of
      ActbetaB and Tgfa is ectopically induced in the thickened eyelid epithelium by
      the FGF10 protein. These results indicate a dual role of FGF10 in mouse eyelid
      development, for both proliferation and coordinated migration of eyelid
      epithelial cells by reorganization of the cytoskeleton, through the regulation of
      activin, TGFalpha and SHH signaling.

PMID- 15958513
TI  - Angiopoietin 1 causes vessel enlargement, without angiogenic sprouting, during a
      critical developmental period.
AB  - Early in development, endothelial cells proliferate, coalesce, and sprout to form
      a primitive plexus of undifferentiated microvessels. Subsequently, this plexus
      remodels into a hierarchical network of different-sized vessels. Although the
      processes of proliferation and sprouting are well studied and are dependent on
      the angiogenic growth factor VEGF, the factors involved in subsequent vessel
      remodeling are poorly understood. Here, we show that angiopoietin 1 can induce
      circumferential vessel enlargement, specifically on the venous side of the
      circulation. This action is due to the ability of angiopoietin 1 to promote
      endothelial cell proliferation in the absence of angiogenic sprouting; vessel
      growth without sprouting has not been ascribed to other vascular growth factors,
      nor has specificity for a particular segment of the vasculature. Moreover,
      angiopoietin 1 potently mediates widespread vessel enlargement only during a
      brief postnatal period, in particular, prior to the fourth postnatal week,
      corresponding to stages in which VEGF inhibition causes widespread vessel
      regression. These findings show that angiopoietin 1 has a potentially unique role
      among the vascular growth factors by acting to enlarge blood vessels without
      inducing sprouting, and also define a critical window of vascular plasticity in
      neonatal development. Finding the key molecular factors that regulate this
      plasticity may prove crucial to the further development of pro- and anti
      angiogenic therapies.

PMID- 15958514
TI  - Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice
      transgenic for the transcription factor Lbh.
AB  - Partial trisomy 2p syndrome includes a spectrum of congenital heart disease (CHD)
      that is characterized by complex malformations of the outflow and inflow tracts,
      defects in cardiac septation, heart position, as well as abnormal ventricular
      development. Lbh (limb-bud and heart) is a novel, highly conserved putative
      transcriptional regulatory protein, which displays a unique spatiotemporal gene
      expression pattern during early mouse heart development. Here we show that human
      LBH maps to chromosome 2p23, a genomic region related to CHD in partial trisomy
      2p syndrome. Remarkably, transgenic overexpression of Lbh in mice throughout the
      embryonic myocardium from a cardiomyocyte-specific promoter of the cardiac
      ankyrin repeat protein gene (Carp/Ankrd1) models CHD reported in humans with
      partial trisomy 2p syndrome. The malformations in Carp-Lbh transgenic mice
      reflect impaired pulmonary outflow tract valvulogenesis, cardiac septation,
      inflow tract morphogenesis, as well as abnormalities in ventricular cardiomyocyte
      growth. Furthermore, we demonstrate that overexpression of Lbh in cultured
      mammalian cells represses the synergistic activity of key cardiac transcription
      factors, Nkx2.5 and Tbx5, leading to reduced activation of the common target
      gene, Anf (Nppa). Strikingly, reduced levels of Anf expression were also observed
      in embryonic day 9.5 Carp-Lbh transgenic mice. Thus, repression of Nkx2.5 and
      Tbx5-mediated gene expression by deregulated Lbh may account in part for the
      cardiac anomalies observed in these mice. Our findings implicate LBH as a
      candidate gene for CHD associated with partial trisomy 2p syndrome and suggest an
      important role of Lbh in transcriptional control during normal cardiogenesis.

PMID- 15958515
TI  - Lineage restriction maintains a stable organizer cell population at the zebrafish
      midbrain-hindbrain boundary.
AB  - The vertebrate hindbrain is subdivided into segments, termed neuromeres, that are
      units of gene expression, cell differentiation and behavior. A key property of
      such segments is that cells show a restricted ability to mix across segment
      borders -- termed lineage restriction. In order to address segmentation in the
      midbrain-hindbrain boundary (mhb) region, we have analyzed single cell behavior
      in the living embryo by acquiring time-lapse movies of the developing mhb region
      in a transgenic zebrafish line. We traced the movement of hundreds of nuclei, and
      by matching their position with the expression of a midbrain marker, we
      demonstrate that midbrain and hindbrain cells arise from two distinct cell
      populations. Single cell labeling and analysis of the distribution of their
      progeny shows that lineage restriction is probably established during late
      gastrulation stages. Our findings suggest that segmentation as an organizing
      principle in early brain development can be extended to the mhb region. We argue
      that lineage restriction serves to constrain the position of the mhb organizer
      cell population.

PMID- 15958516
TI  - Lupeol, a fruit and vegetable based triterpene, induces apoptotic death of human
      pancreatic adenocarcinoma cells via inhibition of Ras signaling pathway.
AB  - Pancreatic cancer is an exceptionally aggressive disease, the treatment of which
      has largely been unsuccessful due to higher resistance offered by pancreatic
      cancer cells to conventional approaches such as surgery, radiation and/or
      chemotherapy. The aberration of Ras oncoprotein has been linked to the induction
      of multiple signaling pathways and to the resistance offered by pancreatic cancer
      cells to apoptosis. Therefore, there is a need for development of new and
      effective chemotherapeutic agents which can target multiple pathways to induce
      responsiveness of pancreatic cancer cells to death signals. In this study, human
      pancreatic adenocarcinoma cells AsPC-1 were used to investigate the effect of
      Lupeol on cell growth and its effects on the modulation of multiple Ras-induced
      signaling pathways. Lupeol caused a dose-dependent inhibition of cell growth as
      assessed by MTT assay and induction of apoptosis as assessed by flow cytometry,
      fluorescence microscopy and western blotting. Lupeol treatment to cells was found
      to significantly reduce the expression of Ras oncoprotein and modulate the
      protein expression of various signaling molecules involved in PKCalpha/ODC,
      PI3K/Akt and MAPKs pathways along with a significant reduction in the activation
      of NFkappaB signaling pathway. Our data suggest that Lupeol can adopt a multi
      prong strategy to target multiple signaling pathways leading to induction of
      apoptosis and inhibition of growth of pancreatic cancer cells. Lupeol could be a
      potential agent against pancreatic cancer, however, further in-depth in vivo
      studies are warranted.

PMID- 15958517
TI  - Mechanisms of chemopreventive effects of 8-methoxypsoralen against 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced mouse lung adenomas.
AB  - Recently we reported that the occurrence of lung adenoma caused by 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was completely prevented by
      pretreatment of female A/J mice with 8-methoxypsoralen, a potent inhibitor of
      cytochrome P450 (P450 or CYP) 2A [Takeuchi et al. (2003) Cancer Res., 63, 7581
      7583]. Thus, the aim of this study was to confirm that 8-methoxypsoralen exhibits
      chemopreventive effects by inhibiting CYP2A in the mouse lung. The involvement of
      CYP2A in the metabolic activation of NNK in the lung was first evidenced by the
      fact that the mutagenic activation of NNK by mouse lung microsomes was inhibited
      by 8-methoxypsoralen, coumarin and antibodies to rat CYP2A1. Supporting this, the
      mutagenic activation of NNK was efficiently catalyzed by mouse CYP2A4 and CYP2A5
      co-expressed with NADPH-P450 reductase in a genetically engineered Salmonella
      typhimurium YG7108. The expression of mRNA for CYP2A5, but not for CYP2A4 or
      CYP2A12, in the mouse lung was proven by reverse transcriptase-polymerase chain
      reaction, probably indicating that CYP2A5 present in the mouse lung was involved
      in the metabolic activation of NNK. In accordance with these in vitro data,
      treatment of gpt delta transgenic mice with 8-methoxypsoralen prior to NNK
      completely inhibited the mutation of the gpt delta gene. The in vivo
      chemopreventive effects of 8-methoxypsoralen towards NNK-induced adenoma was seen
      only when the agent was given to female A/J mice prior to, but not posterior to,
      NNK, lending support to the idea that NNK is activated by CYP2A5 in the mouse
      lung as an initial step to cause adenoma. The inhibition by 8-methoxypsoralen of
      NNK-induced adenoma was seen in a dose-dependent manner: the dose to show
      apparent 50% suppression was calculated to be 1.0 mg/kg. To our surprise, CYP2A
      protein(s) was expressed in the lesion of NNK-induced lung adenomas, probably
      suggesting that 8-methoxypsoralen could inhibit the possible occurrence of
      further mutation of the adenoma cells induced by NNK. Based on these lines of
      evidence, we propose that 8-methoxypsoralen inhibits the CYP2A5-mediated
      metabolic activation of NNK in the mouse lung, leading to the prevention of NNK
      induced adenoma.

PMID- 15958518
TI  - Indole-3-carbinol inhibition of androgen receptor expression and downregulation
      of androgen responsiveness in human prostate cancer cells.
AB  - Indole-3-carbinol (I3C), a naturally occurring compound found in vegetables of
      the Brassica genus, such as broccoli and cabbage, is a promising anticancer agent
      previously shown to induce a G(1) cell-cycle arrest in the cells of human lymph
      node carcinoma of prostate (LNCaP) through regulation of specific G(1)-acting
      cell-cycle components. Since the androgen receptor (AR) mediates proliferation
      and differentiation in the prostate and is expressed in nearly all human prostate
      cancers, the effects of I3C on AR expression and function were examined in LNCaP
      cells. Immunoblot and quantitative RT-PCR assays revealed that I3C inhibited the
      expression of AR protein and mRNA levels within 12 h of indole treatment. I3C
      downregulated the reporter activity of LNCaP cells transiently transfected with
      an AR promoter-luciferase plasmid, demonstrating that a unique response to I3C is
      the inhibition of AR promoter activity. In contrast to I3C, the natural I3C
      dimerization product 3,3'-diindolylmethane, which acts as an androgen antagonist,
      had no effect on AR expression. To determine the functional significance of the
      I3C-inhibited expression of AR, the AR-regulated prostate specific antigen (PSA)
      was utilized as a downstream indicator. I3C downregulated the expression of PSA
      transcripts and protein levels and inhibited PSA promoter activity, as well as
      that of a minimal androgen responsive element containing reporter plasmid.
      Expression of exogenous AR prevented the I3C disruption of androgen-induced PSA
      expression. Taken together, our results demonstrate that I3C represses AR
      expression and responsiveness in LNCaP cells as a part of its antiproliferative
      mechanism.

PMID- 15958519
TI  - The extract of huanglian, a medicinal herb, induces cell growth arrest and
      apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer
      cells.
AB  - Huanglian (Coptidis rhizoma), a widely used herb in traditional Chinese medicine,
      has been shown recently to possess anticancer activities. However, the molecular
      mechanism underlying the anticancer effect of the herb is poorly understood.
      Specifically, whether huanglian extract affects the expression of cancer-related
      genes has not been defined. This study used DNA microarray technology to examine
      the effect of the herbal extract on expression of the common genes involved in
      carcinogenesis in two human breast cancer cell lines, the ER-positive MCF-7 and
      ER-negative MDA-MB-231 cells. Treatment of the cancer cells with huanglian
      extract markedly inhibited their proliferation in a dose- and time-dependent
      manner. The growth inhibitory effect was much more profound in MCF-7 cell line
      than that in MDA-MB-231 cells. DNA microarray assay revealed that treatment with
      huanglian dramatically increased the mRNA expression of interferon-beta (IFN
      beta) and tumor necrosis factor-alpha in MCF-7 cells. Quantitative analysis by
      real-time PCR or western blotting confirmed the upregulation of the two genes
      (especially IFN-beta) in MCF-7 cells, but not in MDA-MB-231 cells. Addition of
      neutralizing antibody against IFN-beta to culture medium markedly inhibited the
      huanglian-induced antiproliferative effect, confirming the involvement of IFN
      beta in the huanglian's effect and also suggesting an autocrine pathway for the
      action of IFN-beta in this setting. Given that IFN-beta is among the most
      important anticancer cytokines, the upregulation of this gene by huanglian is, at
      least in part, responsible for its antiproliferative effect. The results of this
      study implicate huanglian as a promising herb for chemoprevention and
      chemotherapy of certain cancers.

PMID- 15958520
TI  - Differential transcriptional regulation of human telomerase in a cellular model
      representing important genetic alterations in esophageal squamous carcinogenesis.
AB  - Telomerase activity is observed in approximately 90% of human cancer including
      esophageal squamous cell cancer. Normal somatic cells do not display telomerase
      activity on a regular basis. The major mechanism to regulate telomerase activity
      in human cells is the transcriptional control of the catalytic subunit, the human
      reverse transcriptase gene hTERT. However, the manner in which telomerase
      activity is regulated during malignant transformation and whether this regulation
      is influenced by single genetic alterations important in this process are not
      well understood. In this study we investigated the transcriptional regulation and
      activity of human telomerase in a cellular model representing important known
      genetic alterations observed in esophageal cancer. We characterized the
      respective cells with regard to their telomere biology and telomerase expression,
      transcriptional regulation using promoter--as well as electrophoretic mobility
      shift assay--analyses and their promoter methylation status. We could demonstrate
      that telomerase expression and subsequent activity are differentially regulated
      in the progression from normal esophageal epithelial cells to genetically defined
      esophageal cells harboring a specific genetic alteration frequently found in
      esophageal cancer and compared those changes with esophageal cancer cells.
      Whereas primary esophageal cells are mainly regulated by Sp1, in cells harboring
      a genetic alteration as cyclin D1 overexpression other transcription factors like
      E2F and c-myc as well as promoter methylation influence hTERT transcription. This
      model demonstrates that the transcriptional regulation of telomerase is
      influenced by a given genetic alteration important in esophageal cancer, and
      therefore provides new insight in telomerase regulation during carcinogenesis.

PMID- 15958522
TI  - Stabilized HIF-1alpha is superior to VEGF for angiogenesis in skeletal muscle via
      adeno-associated virus gene transfer.
AB  - Therapeutic angiogenesis provides a potential alternative for the treatment of
      cardiovascular ischemic diseases. Vascular endothelial growth factor (VEGF) is an
      important component of the angiogenic response to ischemia. Here we used adeno
      associated virus (AAV) gene delivery to skeletal muscle to examine the effects of
      VEGF vs. a stabilized form of hypoxia-inducible factor-1alpha (HIF-1alpha). The
      recombinant AAVs were injected into mouse tibialis anterior muscle, and their
      effects were analyzed by immunohistochemistry and functional assays. These
      analyses showed that stabilized HIF-1alpha markedly increase capillary sprouting
      and proliferation, whereas VEGF164 or VEGF120 induced only proliferation of
      endothelial cells without formation of proper capillary structures. The Evans
      Blue permeability assay indicated that, unlike VEGF, HIF-1alpha overexpression
      did not increase vascular leakiness in the transduced muscle. Doppler ultrasound
      imaging showed that vascular perfusion in the HIF-1alpha treated muscles was
      significantly enhanced when compared to the controls and not further improved by
      co-expression of the arteriogenic growth factors angiopoietin-1 or platelet
      derived growth factor-B. Our results show that AAV-mediated transduction of a
      stabilized form of HIF-1alpha can circumvent the problems associated with
      overexpression of individual angiogenic growth factors. HIF-1alpha should thus
      offer a potent alternative for pro-angiogenic gene therapy.

PMID- 15958521
TI  - Multiple markers for melanoma progression regulated by DNA methylation: insights
      from transcriptomic studies.
AB  - The incidence of melanoma is increasing rapidly, with advanced lesions generally
      failing to respond to conventional chemotherapy. Here, we utilized DNA microarray
      based gene expression profiling techniques to identify molecular determinants of
      melanoma progression within a unique panel of isogenic human melanoma cell lines.
      When a poorly tumorigenic cell line, derived from an early melanoma, was compared
      with two increasingly aggressive derivative cell lines, the expression of 66
      genes was significantly changed. A similar pattern of differential gene
      expression was found with an independently derived metastatic cell line. We
      further examined these melanoma progression-associated genes via use of a
      tailored TaqMan Low Density Array (LDA), representing the majority of genes
      within our cohort of interest. Considerable concordance was seen between the
      transcriptomic profiles determined by DNA microarray and TaqMan LDA approaches. A
      range of novel markers were identified that correlated here with melanoma
      progression. Most notable was TSPY, a Y chromosome-specific gene that displayed
      extensive down-regulation in expression between the parental and derivative cell
      lines. Examination of a putative CpG island within the TSPY gene demonstrated
      that this region was hypermethylated in the derivative cell lines, as well as
      metastatic melanomas from male patients. Moreover, treatment of the derivative
      cell lines with the DNA methyltransferase inhibitor, 2'-deoxy-5-azacytidine
      (DAC), restored expression of the TSPY gene to levels comparable with that found
      in the parental cells. Additional DNA microarray studies uncovered a subset of 13
      genes from the above-mentioned 66 gene cohort that displayed re-activation of
      expression following DAC treatment, including TSPY, CYBA and MT2A. DAC suppressed
      tumor cell growth in vitro. Moreover, systemic treatment of mice with DAC
      attenuated growth of melanoma xenografts, with consequent re-expression of TSPY
      mRNA. Overall, our data support the hypothesis that multiple genes are targeted,
      either directly or indirectly, by DNA hypermethylation during melanoma
      progression.

PMID- 15958523
TI  - Regulation of CFTR channels by HCO(3)--sensitive soluble adenylyl cyclase in
      human airway epithelial cells.
AB  - CFTR channels conduct HCO(3)(-) in addition to Cl(-) in airway epithelial cells.
      A defective HCO(3)(-)-transporting function of CFTR may underlie the pathogenesis
      of cystic fibrosis. In the present study, we have investigated whether a HCO(3)(
      )-sensitive soluble adenylyl cyclase (sAC) is functionally coupled with CFTR and
      thus forms an autoregulatory mechanism for HCO(3)(-) transport in human airway
      epithelial Calu-3 cells. A reverse transcriptase-polymerase chain reaction showed
      that transcripts of both full-length and truncated sACs are present in Calu-3
      cells. Truncated sAC protein is the predominant, if not the only, isoform
      expressed in Calu-3 cells. HCO(3)(-) stimulated a modest increase in cAMP
      production, and the increase was sensitive to 2-hydroxyestradiol (2-HE), a sAC
      inhibitor, but not to SQ22,536, a blocker of conventional transmembrane adenylyl
      cyclases. These results suggest that sAC is functional in Calu-3 cells. Adding 25
      mM HCO(3)(-) to the bath stimulated CFTR-mediated whole cell currents in the
      absence, but not in the presence, of 2-HE. In cell-attached membrane patches, 25
      or 50 mM HCO(3)(-) in the bath markedly increased the product of channel number
      and open probability of CFTR, and this activation was attenuated by 2-HE. These
      findings demonstrate that sAC signaling pathway is involved in the regulation of
      CFTR function in human airway epithelium and thereby provides a link between the
      level of intracellular HCO(3)(-)/CO(2) and the modulation of HCO(3)(-)-conductive
      CFTR function by cAMP/PKA.

PMID- 15958524
TI  - Immature osteoblastic MG63 cells possess two calcitonin gene-related peptide
      receptor subtypes that respond differently to [Cys(Acm)(2,7)] calcitonin gene
      related peptide and CGRP(8-37).
AB  - Calcitonin gene-related peptide (CGRP) is clearly an anabolic factor in skeletal
      tissue, but the distribution of CGRP receptor (CGRPR) subtypes in osteoblastic
      cells is poorly understood. We previously demonstrated that the CGRPR expressed
      in osteoblastic MG63 cells does not match exactly the known characteristics of
      the classic subtype 1 receptor (CGRPR1). The aim of the present study was to
      further characterize the MG63 CGRPR using a selective agonist of the putative
      CGRPR2, [Cys(Acm)(2,7)]CGRP, and a relatively specific antagonist of CGRPR1,
      CGRP(8-37). [Cys(Acm)(2,7)]CGRP acted as a significant agonist only upon ERK
      dephosphorylation, whereas this analog effectively antagonized CGRP-induced cAMP
      production and phosphorylation of cAMP response element-binding protein (CREB)
      and p38 MAPK. Although it had no agonistic action when used alone, CGRP(8-37)
      potently blocked CGRP actions on cAMP, CREB, and p38 MAPK but had less of an
      effect on ERK. Schild plot analysis of the latter data revealed that the apparent
      pA2 value for ERK is clearly distinguishable from those of the other three plots
      as judged using the 95% confidence intervals. Additional assays using 3-isobutyl
      1-methylxanthine or the PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5
      isoquinolinesulfonamide hydrochloride (H-89) indicated that the cAMP-dependent
      pathway was predominantly responsible for CREB phosphorylation, partially
      involved in ERK dephosphorylation, and not involved in p38 MAPK phosphorylation.
      Considering previous data from Scatchard analysis of [125I]CGRP binding in
      connection with these results, these findings suggest that MG63 cells possess two
      functionally distinct CGRPR subtypes that show almost identical affinity for CGRP
      but different sensitivity to CGRP analogs: one is best characterized as a
      variation of CGRPR1, and the second may be a novel variant of CGRPR2.

PMID- 15958525
TI  - Temporal changes of multiple redox couples from proliferation to growth arrest in
      IEC-6 intestinal epithelial cells.
AB  - Changes in intracellular redox couples and redox reactive molecules have been
      implicated in the regulation of a variety of cellular processes, including cell
      proliferation and growth arrest by contact inhibition. However, the magnitude,
      direction, and temporal relationship of redox changes to cellular responses are
      incompletely defined. The present work sought to characterize redox and metabolic
      changes associated with proliferative stages to contact inhibition of growth in
      rat IEC-6 intestinal epithelial cells. From the first day of culture until 1 day
      before confluence, an increase in GSH concentrations and a significant reduction
      in the redox potential of the GSSG/2GSH couple were observed. These changes were
      accompanied by a decrease in relative reactive oxygen species (ROS) and nitric
      oxide (NO) concentrations and oxidation of the redox potential of the
      NADP(+)/reduced NADP and NAD(+)/NADH couples. Postconfluent cells exhibited a
      significant decrease in GSH concentrations and a significant oxidation of the
      GSSG/2GSH couple. When cell proliferation decreased, relative ROS concentrations
      increased (P < 0.01), whereas NO concentrations remained unchanged, and the
      NAD(+)/NADH couple became more reduced. Together, these data indicate that the
      redox potential of distinct couples varies differentially in both magnitude and
      direction during successive stages of IEC-6 growth. This finding points out the
      difficulty of defining intracellular redox status at particular stages of cell
      growth by examining only one redox species. In addition, the data provide a
      numerical framework for future research of regulatory mechanisms governed by
      distinct intracellular redox couples.

PMID- 15958526
TI  - Heat shock-mediated regulation of MKP-1.
AB  - Heat shock modulates cellular proinflammatory responses, and we have been
      interested in elucidating the mechanisms that govern this modulation. The dual
      specific phosphatase, MAP kinase phosphatase-1 (MKP-1), is an important modulator
      of cellular inflammatory responses, and we recently reported that heat shock
      increases expression of MKP-1. Herein we sought to elucidate the mechanisms by
      which heat shock modulates MKP-1 gene expression. Subjecting RAW264.7 macrophages
      to heat shock increased MKP-1 gene expression in a time-dependent manner.
      Transfection with a wild-type murine MKP-1 promoter luciferase reporter plasmid
      demonstrated that heat shock activates the MKP-1 promoter. When the reporter
      plasmid was transfected into heat shock factor-1 (HSF-1)-null fibroblasts, the
      MKP-1 promoter was activated in response to heat shock in a manner similar to
      that of wild-type fibroblasts with intact HSF-1. Site-directed mutagenesis of two
      potential heat shock elements in the MKP-1 promoter demonstrated that both sites
      are required for basal promoter activity. mRNA stability assays demonstrated that
      heat shock increased MKP-1 mRNA stability compared with cells maintained at 37
      degrees C. Inhibition of p38 MAP kinase activity inhibited heat shock-mediated
      expression of MKP-1. These data demonstrate that heat shock regulates MKP-1 gene
      expression at both the transcriptional and posttranscriptional levels.
      Transcriptional mechanisms are HSF-1 independent but are dependent on putative
      heat shock elements in the MKP-1 promoter. Posttranscriptional mechanisms involve
      increased stability of MKP-1 mRNA that is partially dependent on p38 MAP kinase
      activity. These data demonstrate another potential mechanism by which heat shock
      can modulate inflammation-related signal transduction.

PMID- 15958527
TI  - Functional expression of Kir2.x in human aortic endothelial cells: the dominant
      role of Kir2.2.
AB  - Inward rectifier K(+) channels (Kir) are a significant determinant of endothelial
      cell (EC) membrane potential, which plays an important role in endothelium
      dependent vasodilatation. In the present study, several complementary strategies
      were applied to determine the Kir2 subunit composition of human aortic
      endothelial cells (HAECs). Expression levels of Kir2.1, Kir2.2, and Kir2.4 mRNA
      were similar, whereas Kir2.3 mRNA expression was significantly weaker. Western
      blot analysis showed clear Kir2.1 and Kir2.2 protein expression, but Kir2.3
      protein was undetectable. Functional analysis of endothelial inward rectifier
      K(+) current (I(K)) demonstrated that 1) I(K) current sensitivity to Ba(2+) and
      pH were consistent with currents determined using Kir2.1 and Kir2.2 but not
      Kir2.3 and Kir2.4, and 2) unitary conductance distributions showed two prominent
      peaks corresponding to known unitary conductances of Kir2.1 and Kir2.2 channels
      with a ratio of approximately 4:6. When HAECs were transfected with dominant
      negative (dn)Kir2.x mutants, endogenous current was reduced approximately 50% by
      dnKir2.1 and approximately 85% by dnKir2.2, whereas no significant effect was
      observed with dnKir2.3 or dnKir2.4. These studies suggest that Kir2.2 and Kir2.1
      are primary determinants of endogenous K(+) conductance in HAECs under resting
      conditions and that Kir2.2 provides the dominant conductance in these cells.

PMID- 15958528
TI  - DNA knots reveal a chiral organization of DNA in phage capsids.
AB  - Icosahedral bacteriophages pack their double-stranded DNA genomes to near
      crystalline density and achieve one of the highest levels of DNA condensation
      found in nature. Despite numerous studies, some essential properties of the
      packaging geometry of the DNA inside the phage capsid are still unknown. We
      present a different approach to the problems of randomness and chirality of the
      packed DNA. We recently showed that most DNA molecules extracted from
      bacteriophage P4 are highly knotted because of the cyclization of the linear DNA
      molecule confined in the phage capsid. Here, we show that these knots provide
      information about the global arrangement of the DNA inside the capsid. First, we
      analyze the distribution of the viral DNA knots by high-resolution gel
      electrophoresis. Next, we perform Monte Carlo computer simulations of random
      knotting for freely jointed polygons confined to spherical volumes. Comparison of
      the knot distributions obtained by both techniques produces a topological proof
      of nonrandom packaging of the viral DNA. Moreover, our simulations show that the
      scarcity of the achiral knot 4(1) and the predominance of the torus knot 5(1)
      over the twist knot 5(2) observed in the viral distribution of DNA knots cannot
      be obtained by confinement alone but must include writhe bias in the conformation
      sampling. These results indicate that the packaging geometry of the DNA inside
      the viral capsid is writhe-directed.

PMID- 15958529
TI  - Regulation of lck degradation and refractory state in CD8+ cytotoxic T
      lymphocytes.
AB  - After specific activation, CD8+ cytotoxic T lymphocytes (CTLs) enter a refractory
      state termed activation-induced nonresponsiveness (AINR) that is characterized by
      the inability of T cells to respond to a secondary stimulus. Here, we show that T
      cell receptor triggering results in rapid degradation of the src-family protein
      kinase lck through a mechanism that is proteasome- and lysosome-independent,
      sensitive to cysteine protease inhibitors, and distinct from the pathways
      involved in degradation of ZAP-70 kinase or zeta-chain of the CD3 complex.
      Pharmacologic blockade of lck degradation, as well as transfection of refractory
      cells with an lck expression vector, increased responsiveness of CTLs to repeated
      antigenic challenge. The development or maintenance of AINR was not affected by
      exogenously added IL-2, whereas IL-15 or IFN-alpha restored both lck expression
      and responsiveness of preactivated CTLs. Our results suggest that lck degradation
      plays an important role in the development of AINR in human CTLs and that this
      condition can be reverted by pharmacologic agents or lymphokines that prevent lck
      degradation or induce its expression.

PMID- 15958530
TI  - Production of infectious human papillomavirus independently of viral replication
      and epithelial cell differentiation.
AB  - Papillomaviruses are small DNA viruses that are associated with benign and
      malignant epithelial lesions, including >95% of cervical cancers and
      approximately 20% of head and neck cancers. Because papillomavirus replication
      and virion production are tied to epithelial cell differentiation, infectious
      papillomavirus virion production has been limited to cumbersome organotypic
      cultures and mouse xenografts. Consequent difficulties in obtaining useful
      amounts of wild-type or mutant human papillomavirus (HPV) virions have greatly
      limited studies on many aspects of papillomavirus biology. To overcome these
      limitations, we developed a system to encapsidate the full-length papillomaviral
      genome into infectious virions, independently of viral DNA replication and
      epithelial differentiation. This transient-transfection-based system produces
      >1,000 times more infectious virus per cell culture dish than the much more labor
      intensive organotypic culture. Furthermore, we show that this method allows the
      facile generation of infectious particles containing wild-type, mutant, or
      chimeric papillomaviral genomes, overcoming barriers to studying many facets of
      replication, host interactions, and vaccine and drug development, which has been
      limited by the insufficient availability of infectious virions.

PMID- 15958531
TI  - microRNA172 down-regulates glossy15 to promote vegetative phase change in maize.
AB  - Shoot development in many higher plant species is characterized by phase change,
      where meristems and organs transition from one set of identities to another. The
      transition from a juvenile to adult leaf identity in maize is regulated by the
      APETALA2-like gene glossy15 (gl15). We demonstrate here that increasing gl15
      activity in transgenic maize not only increases the number of leaves expressing
      juvenile traits, but also delays the onset of reproductive development,
      indicating that gl15 plays a primary role in the maintenance of the juvenile
      phase. We also show that the accumulation of a maize microRNA homologous to
      miR172 increases during shoot development and mediates gl15 mRNA degradation.
      These data indicate that vegetative phase change in maize is regulated by the
      opposing actions of gl15 and miR172, with gl15 maintaining the juvenile phase and
      miR172 promoting the transition to the adult phase by down-regulation of gl15.
      Our results also suggest that the balance of activities between APETALA2-like
      genes and miR172 may be a general mechanism for regulating vegetative phase
      change in higher plants.

PMID- 15958532
TI  - Highly effective phosphorylation by G protein-coupled receptor kinase 7 of light
      activated visual pigment in cones.
AB  - Cone photoreceptors show briefer photoresponses than rod photoreceptors. Our
      previous study showed that visual pigment phosphorylation, a quenching mechanism
      of light-activated visual pigment, is much more rapid in cones than in rods.
      Here, we measured the early time course of this rapid phosphorylation with good
      time resolution and directly compared it with the photoresponse time course in
      cones. At the time of photoresponse recovery, almost two phosphates were
      incorporated into a bleached cone pigment molecule, which indicated that the
      visual pigment phosphorylation coincides with the photoresponse recovery. The
      rapid phosphorylation in cones is attributed to very high activity of visual
      pigment kinase [G protein-coupled receptor kinase (GRK) 7] in cones. Because of
      this high activity, cone pigment is readily phosphorylated at very high bleach
      levels, which probably explains why cone photoresponses recover quickly even
      after a very bright light and do not saturate under intense background light. The
      high GRK7 activity is brought about by high content of a highly potent enzyme.
      The expression level of GRK7 was 10 times higher than that of rod kinase (GRK1),
      and the specific activity of a single GRK7 molecule was approximately 10 times
      higher than that of GRK1. The specific activity of GRK7 is the highest among the
      GRKs so far known. Our result seems to explain the response characteristics of
      cone photoreceptors in many aspects, including the nonsaturation of the cone
      responses during daylight vision.

PMID- 15958534
TI  - Bisphosphonates and cancer-induced bone disease: beyond their antiresorptive
      activity.
AB  - Bisphosphonates are primarily known for their ability to inhibit osteoclast
      mediated bone resorption. They are an indispensable part of therapy for patients
      with cancers that cause osteolysis. However, there is now a growing body of
      evidence from preclinical research showing that bisphosphonates also exhibit
      antitumor activity, both in vitro and in vivo. They can affect molecular
      mechanisms of tumor cell adhesion, invasion, and proliferation; reinforce the
      effects of cytotoxic agents in a synergistic manner; and exhibit antiangiogenic
      and immunomodulatory effects. These preclinical findings reveal exciting ways of
      optimizing bisphosphonate therapy in oncology to fully exploit their antitumor
      potential.

PMID- 15958533
TI  - ADAM10 mediates E-cadherin shedding and regulates epithelial cell-cell adhesion,
      migration, and beta-catenin translocation.
AB  - E-cadherin controls a wide array of cellular behaviors, including cell-cell
      adhesion, differentiation, and tissue development. We show here that E-cadherin
      is cleaved specifically by ADAM (a disintegrin and metalloprotease) 10 in its
      ectodomain. Analysis of ADAM10-deficient fibroblasts, inhibitor studies, and RNA
      interference-mediated down-regulation of ADAM10 demonstrated that ADAM10 is
      responsible not only for the constitutive shedding but also for the regulated
      shedding of this adhesion molecule in fibroblasts and keratinocytes. ADAM10
      mediated E-cadherin shedding affects epithelial cell-cell adhesion as well as
      cell migration. Furthermore, the shedding of E-cadherin by ADAM10 modulates the
      beta-catenin subcellular localization and downstream signaling. ADAM10
      overexpression in epithelial cells increased the expression of the beta-catenin
      downstream gene cyclin D1 dose-dependently and enhanced cell proliferation. In
      ADAM10-deficient mouse embryos, the C-terminal E-cadherin fragment is not
      generated, and the full-length protein accumulates, highlighting the in vivo
      relevance for ADAM10 in E-cadherin shedding. Our data strongly suggest that this
      protease constitutes a major regulatory element for the multiple functions of E
      cadherin under physiological as well as pathological conditions.

PMID- 15958535
TI  - Targeting medulloblastoma: small-molecule inhibitors of the Sonic Hedgehog
      pathway as potential cancer therapeutics.
AB  - Medulloblastoma is the most common malignant pediatric brain tumor for which no
      satisfactory treatments exist. The Sonic Hedgehog signaling pathway seems to play
      an important role in the pathology of this disease. Here we review our recent
      demonstration that a small-molecule inhibitor of this pathway can regress tumors
      that arise in a transgenic mouse model of medulloblastoma. These and other
      findings suggest that inhibitors of Sonic Hedgehog signaling may offer an
      effective way to target some malignancies.

PMID- 15958536
TI  - [99mTcOAADT]-(CH2)2-NEt2: a potential small-molecule single-photon emission
      computed tomography probe for imaging metastatic melanoma.
AB  - Evaluation of [99mTc]oxotechnetium(V) complexes of the amine-amide-dithiol (AADT)
      chelates containing tertiary amine substituents as small-molecule probes for the
      diagnostic imaging of metastatic melanoma has shown that technetium-99m-labeled
      AADT-(CH2)2-NEt2 (99mTc-1) has the highest tumor uptake and other favorable
      biological properties. We have, therefore, assessed this agent in a more
      realistic metastatic melanoma model in which, after i.v. tail injection, a highly
      invasive melanoma cell line, B16F10, forms pulmonary tumor nodules in normal
      C57BL6 mice. Small melanotic lesions develop in the lungs and, on histologic
      examination, appear as small black melanoma colonies, increasing in size and
      number with time after tumor cell injection. Groups of mice received tumor cell
      inocula of 2 x 10(5), 4 x 10(5), or 8 x 10(5) B16F10 cells; 14 days later, 2
      hours after 99mTc-1 administration, lung uptake of 2.83 +/- 0.21%, 3.63 +/-
      1.07%, and 4.92 +/- 1.61% injected dose per gram of tissue (% ID/g),
      respectively, was observed, compared with normal lung uptake of 2.13 +/- 0.2%
      ID/g (P < 0.05). Additionally, a higher level of 99mTc-1 accumulation was seen 17
      days after tumor cell inoculation as the lung lesions grew. These in vivo studies
      coupled with additional in vitro and ex vivo assessment show that 99mTc-1 has
      high and specific uptake in melanoma metastases in lungs and can potentially
      follow the temporal growth of these tumors.

PMID- 15958537
TI  - DNA-dependent protein kinase is a molecular target for the development of
      noncytotoxic radiation-sensitizing drugs.
AB  - DNA-dependent protein kinase (DNA-PK)-defective severe combined immunodeficient
      (SCID) mice have a greater sensitivity to ionizing radiation compared with wild
      type mice due to deficient repair of DNA double-strand break. SCID cells were
      therefore studied to determine whether radiosensitization by the specific
      inhibitor of DNA-PK, IC87361, is eliminated in the absence of functional DNA-PK.
      IC87361 enhanced radiation sensitivity in wild-type C57BL6 endothelial cells but
      not in SCID cells. The tumor vascular window model was used to assess IC87361
      induced radiosensitization of SCID and wild-type tumor microvasculature. Vascular
      density was 5% in irradiated SCID host compared with 50% in C57BL6 mice (P <
      0.05). IC87361 induced radiosensitization of tumor microvasculature in wild-type
      mice that resembled the radiosensitive phenotype of tumor vessels in SCID mice.
      Radiosensitization by IC87361 was eliminated in SCID tumor vasculature, which
      lack functional DNA-PK. Irradiated LLC and B16F0 tumors implanted into SCID mice
      showed greater tumor growth delay compared with tumors implanted into either wild
      type C57BL6 or nude mice. Furthermore, LLC tumors treated with radiation and
      IC87361 showed tumor growth delay that was significantly greater than tumors
      treated with radiation alone (P < 0.01 for 3 Gy alone versus 3 Gy + IC87361). DNA
      PK inhibitors induced no cytotoxicity and no toxicity in mouse normal tissues.
      Mouse models deficient in enzyme activity are useful to assess the specificity of
      novel kinase inhibitors. DNA-PK is an important target for the development of
      novel radiation-sensitizing drugs that have little intrinsic cytotoxicity.

PMID- 15958538
TI  - Global gene expression profiling of circulating tumor cells.
AB  - Metastases from primary tumors are responsible for most cancer deaths. It has
      been shown that circulating tumor cells (CTCs) can be detected in the peripheral
      blood of patients with a variety of metastatic cancers and that the presence of
      these cells is associated with poor clinical outcomes. Characterization of CTCs
      in metastatic cancer patients could provide additional information to augment
      management of the disease. Here, we describe a novel approach for the
      identification of molecular markers to detect and characterize CTCs in peripheral
      blood. Using an integrated platform to immunomagnetically isolate and
      immunofluorescently detect CTCs, we obtained blood containing > or = 100 CTCs
      from one metastatic colorectal, one metastatic prostate, and one metastatic
      breast cancer patient. Using the RNA extracted from the CTC-enriched portion of
      the sample and comparing it with the RNA extracted from the corresponding CTC
      depleted portion, for the first time, global gene expression profiles from CTCs
      were generated and a list of cancer-specific, CTC-specific genes was obtained.
      Subsequently, samples immunomagnetically enriched for CTCs from 74 metastatic
      cancer patients and 50 normal donors were used to confirm by quantitative real
      time reverse transcription-PCR CTC-specific expression of selected genes and to
      show that gene expression profiles for CTCs may be used to distinguish normal
      donors from advanced cancer patients as well as to differentiate among the three
      different metastatic cancers. Genes such as AGR2, S100A14, S100A16, FABP1, and
      others were found useful for detection of CTCs in peripheral blood of advanced
      cancer patients.

PMID- 15958539
TI  - Element array by scanning X-ray fluorescence microscopy after cis
      diamminedichloro-platinum(II) treatment.
AB  - Minerals are important for cellular functions, such as transcription and enzyme
      activity, and are also involved in the metabolism of anticancer chemotherapeutic
      compounds. Profiling of intracellular elements in individual cells could help in
      understanding the mechanism of drug resistance in tumors and possibly provide a
      new strategy of anticancer chemotherapy. Using a recently developed technique of
      scanning X-ray fluorescence microscopy (SXFM), we analyzed intracellular elements
      after treatment with cis-diamminedichloro-platinum(II) (CDDP), a platinum-based
      anticancer agent. The images obtained by SXFM (element array) revealed that the
      average Pt content of CDDP-resistant cells was 2.6 times less than that of
      sensitive cells, and the zinc content was inversely correlated with the
      intracellular Pt content. Data suggested that Zn-related detoxification is
      responsible for resistance to CDDP. Of Zn-related excretion factors, glutathione
      was highly correlated with the amount of Zn. The combined treatment of CDDP and a
      Zn(II) chelator resulted in the incorporation of thrice more Pt with the
      concomitant down-regulation of glutathione. We propose that the generation of an
      element array by SXFM opens up new avenues in cancer biology and treatment.

PMID- 15958540
TI  - Systemic gene-directed enzyme prodrug therapy of hepatocellular carcinoma using a
      targeted adenovirus armed with carboxypeptidase G2.
AB  - Hepatocellular carcinoma is the fifth most common cancer worldwide, and there is
      no effective therapy for unresectable disease. We have developed a targeted
      systemic therapy for hepatocellular carcinoma. The gene for a foreign enzyme is
      selectively expressed in the tumor cells and a nontoxic prodrug is then given,
      which is activated to a potent cytotoxic drug by the tumor-localized enzyme. This
      approach is termed gene-directed enzyme prodrug therapy (GDEPT). Adenoviruses
      have been used to target cancer cells, have an intrinsic tropism for liver, and
      are efficient gene vectors. Oncolytic adenoviruses produce clinical benefits,
      particularly in combination with conventional anticancer agents and are well
      tolerated. We rationalized that such adenoviruses, if their expression were
      restricted to telomerase-positive cancer cells, would make excellent gene vectors
      for GDEPT therapy of hepatocellular carcinoma. Here we use an oncolytic
      adenovirus to deliver the prodrug-activating enzyme carboxypeptidase G2 (CPG2) to
      tumors in a single systemic administration. The adenovirus replicated and
      produced high levels of CPG2 in two different hepatocellular carcinoma xenografts
      (Hep3B and HepG2) but not other tissues. GDEPT enhanced the adenovirus-alone
      therapy to elicit tumor regressions in the hepatocellular carcinoma models. This
      is the first time that CPG2 has been targeted and expressed intracellularly to
      effect significant therapy, showing that the combined approach holds enormous
      potential as a tumor-selective therapy for the systemic treatment of
      hepatocellular carcinoma.

PMID- 15958541
TI  - Toll-like receptors on tumor cells facilitate evasion of immune surveillance.
AB  - The signal pathways that trigger tumor cell escape from immune surveillance are
      incompletely understood. Toll-like receptors (TLRs), which activate innate and
      adaptive immune responses, are thought to be restricted to immune cells. We show
      here that TLRs, including TLR4, are expressed on tumor cells from a wide variety
      of tissues, suggesting that TLR activation may be an important event in tumor
      cell immune evasion. Activation of TLR4 signaling in tumor cells by
      lipopolysaccharide induces the synthesis of various soluble factors and proteins
      including interleukin-6, inducible nitric oxide synthase, interleukin-12, B7-H1,
      and B7-H2, and results in resistance of tumor cells to CTL attack. In addition,
      lipopolysaccharide-stimulated tumor cell supernatants inhibit both T cell
      proliferation and natural killer cell activity. Blockade of the TLR4 pathway by
      either TLR4 short interfering RNA or a cell-permeable TLR4 inhibitory peptide
      reverses tumor-mediated suppression of T cell proliferation and natural killer
      cell activity in vitro, and in vivo, delays tumor growth and thus prolongs the
      survival of tumor-bearing mice. These findings indicate that TLR signaling
      results in a cascade leading to tumor evasion from immune surveillance. These
      novel functions of TLRs in tumor biology suggest a new class of therapeutic
      targets for cancer therapy.

PMID- 15958542
TI  - Association of genetic polymorphisms in the VEGF gene with breast cancer
      survival.
AB  - The vascular endothelial growth factor (VEGF) is an important regulator of
      angiogenesis and vascular permeability. VEGF overexpression has been associated
      with advanced stage and poor survival of several cancers. We evaluated the
      association of functional polymorphisms in the VEGF gene with breast cancer
      survival in a cohort of 1,193 breast cancer patients who were recruited as part
      of a population-based case-control study in Shanghai, China from 1996 to 1998 and
      followed for cancer recurrence and mortality between March 2000 and December
      2002. Included in the study were three functional polymorphisms (C-460T, G+405C,
      and C+936T) in the VEGF gene. Carrying the -460C or +405G allele was associated
      with decreased overall survival. The age-adjusted hazard ratios (HR) were 1.5
      [95% confidence interval (95% CI), 0.9-2.5] for -460CC genotype carriers and 1.6
      (95% CI, 1.0-2.5) for +405GG genotype carriers compared with noncarriers. Further
      analyses showed that the -460T/+450C/+936C haplotype was related to increased
      survival (HR, 0.57; 95% CI, 0.4-0.9), whereas the -460C/+405G/+936T haplotype was
      associated with nonsignificantly decreased survival (HR, 2.1; 95% CI, -0.9 to
      4.7). The C+936T polymorphism alone was not related to overall or disease-free
      survival. This study suggests that VEGF polymorphisms may be a significant
      genetic marker for breast cancer prognosis.

PMID- 15958543
TI  - Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian
      carcinoma.
AB  - To directly dissect the role of each immune component in human tumor
      immunopathogenesis, we have studied the interaction between dendritic cells and T
      cells in the tumor environment of patients with ovarian carcinoma. We previously
      reported that functional plasmacytoid dendritic cells, but not functionally
      mature myeloid dendritic cells, accumulated in tumor microenvironments. We now
      show that tumor ascites macrophage-derived dendritic cells induced tumor
      associated antigen-specific CD8+ T cells with effector functions. Strikingly,
      tumor ascites plasmacytoid dendritic cells induced interleukin-10+ CCR7+ CD45RO+
      CD8+ regulatory T cells. Four characteristics have been identified in tumor
      plasmacytoid dendritic cell-induced CD8+ regulatory T cells: (a) induction of
      CD8+ regulatory T cells is independent of CD4+ CD25+ T cells; (b) CD8+ regulatory
      T cells significantly suppress myeloid dendritic cell-mediated tumor-associated
      antigen-specific T cell effector functions through interleukin-10; (c) repetitive
      myeloid dendritic cell stimulation can recover CD8+ regulatory T cell-mediated
      poor T cell proliferation, but not T cell effector function; (d) CD8+ regulatory
      T cells express functional CCR7, and efficiently migrate with lymphoid homing
      chemokine MIP-3beta. Primary suppressive CCR7+ CD45RO+ CD8+ T cells are found in
      the tumor environment of patients with ovarian cancers. Thus, tumor-associated
      plasmacytoid dendritic cells contribute to the tumor environmental
      immunosuppressive network. Collectively, tumors manipulate tumor
      microenvironmental dendritic cell subset distribution and function to subvert
      tumor immunity. The data are relevant to understanding tumor immunopathology as
      well as reevaluating tumor immunotherapeutic strategies.

PMID- 15958544
TI  - Immunostimulatory effects of low-dose cyclophosphamide are controlled by
      inducible nitric oxide synthase.
AB  - Cyclophosphamide is a widely used chemotherapeutic drug that was recently applied
      as either an antiangiogenic/antivasculogenic or an immunostimulatory agent in
      combination with cancer immunotherapies. It has been previously shown that
      cyclophosphamide augments the efficacy of antitumor immune responses by depleting
      CD4+ CD25+ T regulatory cells and increasing both T-lymphocyte proliferation and
      T memory cells. Furthermore, cyclophosphamide was shown to mediate killing of
      circulating endothelial progenitors. However, the molecular basis for these
      observations has not yet been elucidated. We show here that the cyclophosphamide
      mediated inhibition of inducible nitric oxide synthase is directly linked to its
      immunostimulatory but not to its antivasculogenic effects. Moreover, combined
      application of cyclophosphamide with a novel, oral DNA vaccine targeting platelet
      derived growth factor B (PDGF-B), overexpressed by proliferating endothelial
      cells in the tumor vasculature, not only completely inhibited the growth of
      different tumor types but also led to tumor rejections in mice. These findings
      provide a new rationale at the molecular level for the combination of
      chemotherapy and immunotherapy in cancer treatment.

PMID- 15958545
TI  - Gene expression profiling of microsatellite unstable and microsatellite stable
      endometrial cancers indicates distinct pathways of aberrant signaling.
AB  - Microsatellite instability (MSI) is a molecular phenotype present in
      approximately 25% of endometrial cancers. We examined the global gene expression
      profiles of early-stage endometrioid endometrial cancers with and without the MSI
      phenotype to test the hypothesis that MSI phenotype may determine a unique
      molecular signature among otherwise similar cancers. Unsupervised principal
      component analysis of the expression data from these cases indicated two distinct
      groupings of cancers based on MSI phenotype. A relatively small number of array
      features (392) at high statistical value (P < 0.001) were identified that drive
      the instability signature in these cancers; 109 of these transcripts differed by
      at least 2-fold. These data identify distinct gene expression profiles for MSI
      and microsatellite stable (MSS) cancers, which suggest that cancers with MSI
      develop in part by different mechanisms from their similar stable counterparts.
      In particular, we found evidence that two members of the secreted frizzled
      related protein family (SFRP1 and SFRP4) were more frequently down-regulated in
      MSI cancers as compared with MSS cancers. Down-regulation was accompanied by
      promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI
      cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target
      fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These
      data classify histologically similar endometrioid endometrial cancers into two
      distinct groupings with implications affecting therapy and prevention.

PMID- 15958546
TI  - Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth
      factors (VEGF-A, VEGF-C) in esophageal adenocarcinoma.
AB  - Cyclooxygenases (COX), especially COX-2, are considered to be involved in
      carcinogenesis. Our study was initiated to test whether expression of COX
      isoforms (COX-1 and COX-2) is linked to expression of potent inducers of
      angiogenesis [vascular endothelial growth factor (VEGF)-A] and lymphangiogenesis
      (VEGF-C) in esophageal adenocarcinoma. One hundred twenty-three esophageal
      adenocarcinomas were investigated by means of quantitative reverse transcription
      PCR for expression of COX-1, COX-2, VEGF-A, and VEGF-C. Additionally, COX-2
      protein expression was determined using immunohistochemistry. Three esophageal
      cancer cell lines (OE-33, OSC-1, and OSC-2) were treated with COX-inhibiting
      substances (diclofenac, rofecoxib, and SC-560) and the effect on expression of
      the four genes was determined. COX-2 protein expression was found in all
      carcinomas under analysis. RNA expression levels of COX-1 and COX-2 varied
      markedly in carcinoma tissues and correlated significantly with each other (P <
      0.001, r = 0.726). Furthermore, COX expression correlated with expression of VEGF
      A (COX-1: P < 0.001, r = 0.753; COX-2: P < 0.001, r = 0.764) and VEGF-C (COX-1: P
      < 0.001, r = 0.778; COX-2: P < 0.001; r = 0.613). Exposure of esophageal cancer
      cell lines OE-33, OSC-1, and OSC-2 with three COX-inhibiting substances
      (diclofenac, rofecoxib, and SC-560) resulted in significantly reduced expression
      of VEGF-A and VEGF-C. In conclusion, our data suggest that both COX isoforms may
      be involved in the pathogenesis of esophageal adenocarcinoma, as they are linked
      to the expression of important modulators of angiogenesis (VEGF-A) and
      lymphangiogenesis (VEGF-C).

PMID- 15958547
TI  - In vitro modeling of human pancreatic duct epithelial cell transformation defines
      gene expression changes induced by K-ras oncogenic activation in pancreatic
      carcinogenesis.
AB  - Genetic analysis of pancreatic ductal adenocarcinomas and their putative
      precursor lesions, pancreatic intraepithelial neoplasias (PanIN), has shown a
      multistep molecular paradigm for duct cell carcinogenesis. Mutational activation
      or inactivation of the K-ras, p16(INK4A), Smad4, and p53 genes occur at
      progressive and high frequencies in these lesions. Oncogenic activation of the K
      ras gene occurs in >90% of pancreatic ductal carcinoma and is found early in the
      PanIN-carcinoma sequence, but its functional roles remain poorly understood. We
      show here that the expression of K-ras(G12V) oncogene in a near diploid HPV16
      E6E7 gene immortalized human pancreatic duct epithelial cell line originally
      derived from normal pancreas induced the formation of carcinoma in 50% of severe
      combined immunodeficient mice implanted with these cells. A tumor cell line
      established from one of these tumors formed ductal cancer when implanted
      orthotopically. These cells also showed increased activation of the mitogen
      activated protein kinase, AKT, and nuclear factor-kappaB pathways. Microarray
      expression profiling studies identified 584 genes whose expression seemed
      specifically up-regulated by the K-ras oncogene expression. Forty-two of these
      genes have been reported previously as differentially overexpressed in pancreatic
      cancer cell lines or primary tumors. Real-time PCR confirmed the overexpression
      of a large number of these genes. Immunohistochemistry done on tissue microarrays
      constructed from PanIN and pancreatic cancer samples showed laminin beta3
      overexpression starting in high-grade PanINs and occurring in >90% of pancreatic
      ductal carcinoma. The in vitro modeling of human pancreatic duct epithelial cell
      transformation may provide mechanistic insights on gene expression changes that
      occur during multistage pancreatic duct cell carcinogenesis.

PMID- 15958548
TI  - Identification of a genetic signature of activated signal transducer and
      activator of transcription 3 in human tumors.
AB  - Signal transducer and activator of transcription 3 (STAT3) is a transcription
      factor that is activated in diverse human tumors and may play a direct role in
      malignant transformation. However, the full complement of target genes that STAT3
      regulates to promote oncogenesis is not known. We created a system to express a
      constitutively active form of STAT3, STAT3-C, in mouse fibroblasts and used it to
      identify STAT3 targets. We showed that a subset of these targets, which include
      transcription factors regulating cell growth, survival, and differentiation, are
      coexpressed in a range of human tumors. Using immunohistochemical staining of
      tissue microarrays, we showed that these targets are enriched in breast and
      prostate tumors harboring activated STAT3. Finally, we showed that STAT3 is
      required for the expression of these genes in a breast cancer cell line. Taken
      together, these results identify a cohort of STAT3 targets that may mediate its
      role in oncogenesis.

PMID- 15958549
TI  - Bcl-2 acts in a proangiogenic signaling pathway through nuclear factor-kappaB and
      CXC chemokines.
AB  - Vascular endothelial growth factor (VEGF) induces expression of Bcl-2 in tumor
      associated microvascular endothelial cells. We have previously reported that up
      regulated Bcl-2 expression in microvascular endothelial cells is sufficient to
      enhance intratumoral angiogenesis and to accelerate tumor growth. We initially
      attributed these results to Bcl-2-mediated endothelial cell survival. However, in
      recent experiments, we observed that conditioned medium from Bcl-2-transduced
      human dermal microvascular endothelial cells (HDMEC-Bcl-2) is sufficient to
      induce potent neovascularization in the rat corneal assay, whereas conditioned
      medium from empty vector controls (HDMEC-LXSN) does not induce angiogenesis.
      These results cannot be attributed to the role of Bcl-2 in cell survival. To
      understand this unexpected observation, we did gene expression arrays that
      revealed that the expression of the proangiogenic chemokines interleukin-8
      (CXCL8) and growth-related oncogene-alpha (CXCL1) is significantly higher in
      HDMEC exposed to VEGF and in HDMEC-Bcl-2 than in controls. Inhibition of Bcl-2
      expression with small interfering RNA-Bcl-2, or the inhibition of Bcl-2 function
      with small molecule inhibitor BL-193, down-regulated CXCL8 and CXCL1 expression
      and caused marked decrease in the angiogenic potential of endothelial cells
      without affecting cell viability. Nuclear factor-kappaB (NF-kappaB) is highly
      activated in HDMEC exposed to VEGF and HDMEC-Bcl-2 cells, and genetic and
      chemical approaches to block the activity of NF-kappaB down-regulated CXCL8 and
      CXCL1 expression levels. These results reveal a novel function for Bcl-2 as a
      proangiogenic signaling molecule and suggest a role for this pathway in tumor
      angiogenesis.

PMID- 15958550
TI  - Meningioma transcript profiles reveal deregulated Notch signaling pathway.
AB  - Meningiomas constitute the second most common central nervous system tumor, and
      yet relatively little is known about the molecular events that are important for
      the pathogenesis and malignant progression of these tumors. We have used serial
      analysis of gene expression to compare the transcriptomes of nonneoplastic
      meninges and meningiomas of all malignancy grades. A novel finding from this
      screen is the induction of three components of the Notch signaling pathway: the
      transcription factor, hairy and enhancer of Split1 (HES1) and two members of the
      Groucho/transducin-like enhancer of Split family of corepressors, TLE2 and TLE3.
      TLE corepressors interact and modulate the activity of a wide range of
      transcriptional regulatory systems, one of which is HES1. We have shown that the
      transcript and protein levels of HES1, the Notch2 and Notch1 receptors and the
      Jagged1 ligand are induced in meningiomas of all grades, whereas induction of
      TLE2 and TLE3 occurs specifically in higher-grade meningiomas. Meningioma cell
      lines express components of the Notch signaling pathway and an inhibitor of this
      pathway suppresses meningioma cell survival. These results suggest that
      deregulated expression of the Notch pathway is a critical event in meningioma
      pathogenesis and that modulation of this and potentially other signaling pathways
      by TLE corepressors leads to a more malignant phenotype.

PMID- 15958551
TI  - TP53 and KRAS mutation load and types in lung cancers in relation to tobacco
      smoke: distinct patterns in never, former, and current smokers.
AB  - TP53 mutations are common in lung cancers of smokers, with high prevalence of G:C
      to-T:A transversions generally interpreted as mutagen fingerprints of tobacco
      smoke. In this study, TP53 (exons 5-9) and KRAS (codon 12) were analyzed in
      primary lung tumors of never (n = 40), former (n = 27), and current smokers (n =
      64; mainly heavy smokers). Expression of p53, cyclooxygenase-2 (Cox-2), and
      nitrotyrosine (N-Tyr), a marker of protein damage by nitric oxide, were analyzed
      by immunohistochemistry. TP53 mutations were detected in 47.5% never, 55.6%
      former, and 77.4% current smokers. The relative risk for mutation increased with
      tobacco consumption (P(linear trend) < 0.0001). G:C-to-T:A transversions (P =
      0.06, current versus never smokers) and A:T-to-G:C transitions (P = 0.03, former
      versus never smokers) were consistently associated with smoking. In contrast, G:C
      to-A:T transitions were associated with never smoking (P = 0.02). About half of
      mutations in current smokers fell within a particular domain of p53 protein,
      suggesting a common structural effect. KRAS mutations, detected in 20 of 131
      (15.3%) cases, were rare in squamous cell carcinoma compared with adenocarcinoma
      [relative risk (RR), 0.2; 95% confidence interval (95% CI), 0.07-1] and were more
      frequent in former smokers than in other categories. No significant differences
      in Cox-2 expression were found between ever and never smokers. However, high
      levels of N-Tyr were more common in never than ever smokers (RR, 10; 95% CI, 1.6
      50). These results support the notion that lung tumorigenesis proceeds through
      different molecular mechanisms according to smoking status. In never smokers,
      accumulation of N-Tyr suggests an etiology involving severe inflammation.

PMID- 15958552
TI  - Novel cellular genes essential for transformation of endothelial cells by
      Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is involved in the development of
      lymphoproliferative diseases and Kaposi's sarcoma. The oncogenicity of this virus
      is reflected in vitro by its ability to transform B cells and endothelial cells.
      Infection of dermal microvascular endothelial cells (DMVEC) transforms the cells
      from a cobblestone-like monolayer to foci-forming spindle cells. This
      transformation is accompanied by dramatic changes in the cellular transcriptome.
      Known oncogenes, such as c-Kit, are among the KSHV-induced host genes. We
      previously showed that c-Kit is an essential cellular component of the KSHV
      mediated transformation of DMVEC. Here, we test the hypothesis that the
      transformation process can be used to discover novel oncogenes. When expression
      of a panel of KSHV-induced cellular transcripts was inhibited with antisense
      oligomers, we observed inhibition of DMVEC proliferation and foci formation using
      antisense molecules to RDC1 and Neuritin. We further showed that transformation
      of KSHV-infected DMVEC was inhibited by small interfering RNA directed at RDC1 or
      Neuritin. Ectopic expression of Neuritin in NIH 3T3 cells resulted in changes in
      cell morphology and anchorage-independent growth, whereas RDC1 ectopic expression
      significantly increased cell proliferation. In addition, both RDC1- and Neuritin
      expressing cells formed tumors in nude mice. RDC1 is an orphan G protein-coupled
      receptor, whereas Neuritin is a growth-promoting protein known to mediate neurite
      outgrowth. Neither gene has been previously implicated in tumorigenesis. Our data
      suggest that KSHV-mediated transformation involves exploitation of the hitherto
      unrealized oncogenic properties of RDC1 and Neuritin.

PMID- 15958553
TI  - A genomic map of p53 binding sites identifies novel p53 targets involved in an
      apoptotic network.
AB  - The transcriptional activity of the p53 protein is central to its role in tumor
      suppression. Identification of the complete repertoire of p53-regulated genes is
      critical for dissecting the complexity of the p53 network. Although several
      different approaches have been used to characterize the p53 genetic program, we
      still lack a comprehensive molecular understanding of how p53 prevents cancer.
      Using a computational approach, we generated a genome-wide map of p53 binding
      sites (p53BS) to identify novel p53 target genes. We show that the presence of
      nearby p53BS can identify new proapoptotic members of the Bcl2 family. We show
      that p53 binds to p53BS identified in the BCL-G/BCL2L14 gene and that induction
      of this gene contributes to p53-mediated apoptosis. We found that p53 activates
      the COL18A1 gene encoding the precursor for the antiangiogenic factor endostatin.
      We also show that p53 up-regulates the MAP4K4 gene and activates the c-Jun NH2
      terminal kinase (JNK) pathway to drive apoptosis. Thus, unbiased mapping of the
      genomic landscape of p53BS provides a systematic and complementary approach to
      identify novel factors and connections in the p53 genetic network. Our study
      illustrates how systematic genomic approaches can identify binding sites that are
      functionally relevant for a p53 transcriptional program. The genetic link among
      p53, antiangiogenic factors, and the JNK signaling pathway adds new dimensions to
      understanding p53 function in highly connected genetic networks.

PMID- 15958554
TI  - Characterization of common CYP1B1 variants with different capacity for
      benzo[a]pyrene-7,8-dihydrodiol epoxide formation from benzo[a]pyrene.
AB  - Cytochrome P450 1B1 (CYP1B1), an extrahepatic enzyme inducible by smoking, is
      overexpressed in many tumors and catalyzes the metabolic activation of
      procarcinogens such as polycyclic aromatic hydrocarbons. In human, CYP1B1 is
      genetically polymorphic and five common missense mutations causing amino acid
      substitution have been identified. In this study, we have investigated CYP1B1
      haplotypes present in a Spanish population and carried out functional analyses of
      the corresponding enzymes in yeast using benzo[a]pyrene as a substrate. CYP1B1*1,
      CYP1B1*2, CYP1B1*3, CYP1B1*4, CYP1B1*6, and CYP1B1*7, encoding combinations of
      the Arg48Gly, Ala119Ser, Leu432Val, Asn453Ser, and Ala443Gly amino acid
      substitutions, were present at frequencies of 14.3%, 25.5%, 38.8%, 18.1%, 0.4%,
      and 2.6%, respectively. The variant CYP1B1 forms were heterologously expressed
      with human reductase in Saccharomyces cerevisiae and kinetic analyses of
      benzo[a]pyrene metabolism were carried out. CYP1B1.7, having the amino acid
      substitutions Arg48Gly, Ala119Ser, Leu432Val, and Ala443Gly, exhibited a
      significantly decreased capacity (P < 0.001) for the formation of (+/-)
      benzo[a]pyrene-trans-7,8-dihydrodiol from benzo[a]pyrene as indicated by lower
      intrinsic clearance (Vmax/Km). A somewhat decreased clearance was observed for
      CYP1B1.4, whereas no significant differences in kinetic properties among the
      remaining variant enzymes were observed as compared with CYP1B1.1. Thus, genetic
      polymorphism in the CYP1B1 gene, as defined by the haplotypes investigated, might
      cause interindividual differences in susceptibility (e.g., to lung cancer induced
      by smoking). The results indicate the necessity to make molecular epidemiologic
      investigations regarding the association of the specific CYP1B1 haplotypes and
      cancer risk.

PMID- 15958555
TI  - Heightened expression of CTCF in breast cancer cells is associated with
      resistance to apoptosis.
AB  - CTCF is a candidate tumor suppressor gene encoding a multifunctional
      transcription factor. Surprisingly for a tumor suppressor, the levels of CTCF in
      breast cancer cell lines and tumors were found elevated compared with breast cell
      lines with finite life span and normal breast tissues. In this study, we aimed to
      investigate the possible cause for this increase in CTCF content and in
      particular to test the hypothesis that up-regulation of CTCF may be linked to
      resistance of breast cancer cells to apoptosis. For this purpose, apoptotic cell
      death was monitored following alterations of CTCF levels induced by transient
      transfection and conditional knockdown of CTCF in various cell lines. We observed
      apoptotic cell death in all breast cancer cell lines examined following CTCF down
      regulation. In addition, overexpression of CTCF partially protected cells from
      apoptosis induced by overexpression of Bax or treatment with sodium butyrate. To
      elucidate possible mechanisms of this phenomenon, we used a proteomics approach
      and observed that levels of the proapoptotic protein, Bax, were increased
      following CTCF down-regulation in MCF7 cells. Taken together, these results
      suggest that in some cellular contexts CTCF shows antiapoptotic characteristics,
      most likely exerting its functions through regulation of apoptotic genes. We
      hypothesize that CTCF overexpression may have evolved as a compensatory mechanism
      to protect breast cancer cells from apoptosis, thus providing selective survival
      advantages to these cells. The observations reported in this study may lead to
      development of therapies based on selective reduction of CTCF in breast cancer
      cells.

PMID- 15958556
TI  - Secreted protein acidic and rich in cysteine produced by human melanoma cells
      modulates polymorphonuclear leukocyte recruitment and antitumor cytotoxic
      capacity.
AB  - The expression of secreted protein acidic and rich in cysteine (SPARC) has been
      associated with the malignant progression of different types of human cancer.
      SPARC was associated with tumor cell capacity to migrate and invade, although its
      precise role in tumor progression is still elusive. In the present study, we show
      that SPARC produced by melanoma cells modulates the antitumor activity of
      polymorphonuclear leukocytes (PMN). Administration to nude mice of human melanoma
      cells in which SPARC expression was transiently or stably knocked down by
      antisense RNA (SPARC-sup cells) promoted PMN recruitment and obliterated tumor
      growth even when SPARC-sup cells accounted for only 10% of injected malignant
      cells. In addition, SPARC-sup cells stimulated the in vitro migration and
      triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was
      reverted in the presence of SPARC purified from melanoma cells or by reexpressing
      SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and growth-related
      oncogene, in combination with Fas ligand and interleukin 1, mediated SPARC
      effects. These data indicate that SPARC plays an essential role in tumor evasion
      from immune surveillance through the inhibition of the antitumor PMN activity.

PMID- 15958557
TI  - Early growth response 1 acts as a tumor suppressor in vivo and in vitro via
      regulation of p53.
AB  - The early growth response 1 (Egr1) gene is a transcription factor that acts as
      both a tumor suppressor and a tumor promoter. Egr1-null mouse embryo fibroblasts
      bypass replicative senescence and exhibit a loss of DNA damage response and an
      apparent immortal growth, suggesting loss of p53 functions. Stringent expression
      analysis revealed 266 transcripts with >2-fold differential expression in Egr1
      null mouse embryo fibroblasts, including 143 known genes. Of the 143 genes,
      program-assisted searching revealed 66 informative genes linked to Egr1. All 66
      genes could be placed on a single regulatory network consisting of three branch
      points of known Egr1 target genes: TGFbeta1, IL6, and IGFI. Moreover, 19
      additional genes that are known targets of p53 were identified, indicating that
      p53 is a fourth branch point. Electrophoretic mobility shift assay as well as
      chromatin immunoprecipitation confirmed that p53 is a direct target of Egr1.
      Because deficient p53 expression causes tumors in mice, we tested the role of
      Egr1 in a two-step skin carcinogenesis study (144 mice) that revealed a uniformly
      accelerated development of skin tumors in Egr1-null mice (P < 0.005). These
      studies reveal a new role for Egr1 as an in vivo tumor suppressor.

PMID- 15958558
TI  - Two functional epitopes of pigment epithelial-derived factor block angiogenesis
      and induce differentiation in prostate cancer.
AB  - Pigment epithelial-derived factor (PEDF), an angiogenesis inhibitor with
      neurotrophic properties, balances angiogenesis in the eye and blocks tumor
      progression. Its neurotrophic function and the ability to block vascular leakage
      is replicated by the PEDF 44-mer peptide (residues 58-101). We analyzed PEDFs'
      three-dimensional structure and identified a potential receptor-binding surface.
      Seeking PEDF-based antiangiogenic agents we generated and tested peptides
      representing the middle and lower regions of this surface. We identified
      previously unknown antiangiogenic epitopes consisting of the 34-mer (residues 24
      57) and a shorter proximal peptide (TGA, residues 16-26) with the critical
      stretch L19VEEED24 and a fragment within the 44-mer (ERT, residues 78-94), which
      retained neurotrophic activity. The 34-mer and TGA, but not the 44-mer reproduced
      PEDF angioinhibitory signals hinged on c-jun-NH2-kinase-dependent nuclear factor
      of activated T cell deactivation and caused apoptosis. Conversely, the ERT, but
      not the 34-mer/TGA induced neuronal differentiation. For the 44-mer/ERT, we
      showed a novel ability to cause neuroendocrine differentiation in prostate cancer
      cells. PEDF and the peptides bound endothelial and PC-3 prostate cancer cells.
      Bound peptides were displaced by PEDF, but not by each other, suggesting multiple
      receptors. PEDF and its active fragments blocked tumor formation when
      conditionally expressed by PC-3 cells. The 34- and 44-mer used distinct
      mechanisms: the 34-mer acted on endothelial cells, blocked angiogenesis, and
      induced apoptosis whereas 44-mer prompted neuroendocrine differentiation in
      cancer cells. Our results map active regions for the two PEDF functions,
      signaling via distinct receptors, identify candidate peptides, and provide their
      mechanism of action for future development of PEDF-based tumor therapies.

PMID- 15958559
TI  - Up-regulation of TWIST in prostate cancer and its implication as a therapeutic
      target.
AB  - Androgen-independent metastatic prostate cancer is the main obstacle in the
      treatment of this cancer. Unlike a majority of solid cancers, prostate cancer
      usually shows poor response to chemotherapeutic drugs. In this study, we have
      shown a potential novel target, TWIST, a highly conserved bHLH transcription
      factor, in the treatment of prostate cancer. Using malignant and nonmalignant
      prostate tissues, we found that TWIST expression was highly expressed in the
      majority (90%) of prostate cancer tissues but only in a small percentage (6.7%)
      of benign prostate hyperplasia. In addition, the TWIST expression levels were
      positively correlated with Gleason grading and metastasis, indicating its role in
      the development and progression of prostate cancer. Furthermore, down-regulation
      of TWIST through small interfering RNA in androgen-independent prostate cancer
      cell lines, DU145 and PC3, resulted in increased sensitivity to the anticancer
      drug taxol-induced cell death which was associated with decreased Bcl/Bax ratio,
      leading to activation of the apoptosis pathway. More importantly, inactivation of
      TWIST suppressed migration and invasion abilities of androgen-independent
      prostate cancer cells, which was correlated with induction of E-cadherin
      expression as well as morphologic and molecular changes associated with
      mesenchymal to epithelial transition. These results were further confirmed on the
      androgen-dependent LNCaP cells ectopically expressing the TWIST protein. Our
      results have identified TWIST as a critical regulator of prostate cancer cell
      growth and suggest a potential therapeutic approach to inhibit the growth and
      metastasis of androgen-independent prostate cancer through inactivation of the
      TWIST gene.

PMID- 15958560
TI  - Spatial heterogeneity and oxygen dependence of glucose consumption in R3230Ac and
      fibrosarcomas of the Fischer 344 rat.
AB  - To examine the oxygen-dependence of glucose consumption in solid tumors, we
      monitored gradients of glucose, lactate, and hypoxia in R3230Ac and FSA tumors
      growing in Fischer 344 rats. Bioluminescence imaging, detection of Hoechst 33342,
      and immunostaining of the hypoxia marker EF5 [2-8-N-(2,2,3,3,3
      pentafluoropropyl)acetamide] were done in serial tumor slices. Glucose and
      lactate levels were also determined in liver and blood. Cells were further tested
      for glucose consumption and lactate production in vitro. In both tumor types, EF5
      staining indicated similar maximum levels of hypoxia; the most intense staining
      occurred in perinecrotic regions. Glucose concentrations were highest in liver,
      declined from blood to tumor edge, further into vital tumor regions, and were
      lowest close to necrosis. Glucose was significantly lower in FSA than in R3230Ac
      tumors. Glucose concentrations in R3230Ac tumors were consistently higher in
      nonhypoxic than in hypoxic areas, with maximum values equal to systemic blood
      levels. Glucose in FSA tumors was close to zero, regardless of the presence or
      absence of hypoxia. Lactate did not differ significantly between the tumor types.
      FSA cells in culture showed a trend towards higher aerobic glucose consumption
      versus R3230Ac. Both cell lines increased their lactate production to similar
      levels under hypoxia. We conclude that both R3230Ac and FSA tumors retain the
      Pasteur effect, i.e., hypoxia triggers increased glycolysis. However, our results
      imply that increased aerobic glucose utilization leads to low glucose levels in
      FSA and a situation where supply limits uptake. This explains the repeatedly
      observed correlation between tumor blood flow and 18F-deoxyglucose uptake.

PMID- 15958561
TI  - Somatic induction of Pten loss in a preclinical astrocytoma model reveals major
      roles in disease progression and avenues for target discovery and validation.
AB  - High-grade astrocytomas are invariably deadly and minimally responsive to
      therapy. Pten is frequently mutated in aggressive astrocytoma but not in low
      grade astrocytoma. However, the Pten astrocytoma suppression mechanisms are
      unknown. Here we introduced conditional null alleles of Pten (Pten(loxp/loxp))
      into a genetically engineered mouse astrocytoma model [TgG(deltaZ)T121] in which
      the pRb family proteins are inactivated specifically in astrocytes. Pten
      inactivation was induced by localized somatic retroviral (MSCV)-Cre delivery.
      Depletion of Pten function in adult astrocytoma cells alleviated the apoptosis
      evoked by pRb family protein inactivation and also induced tumor cell invasion.
      In primary astrocytes derived from TgG(deltaZ)T121; Pten(loxp/loxp) mice, Pten
      deficiency resulted in a marked increase in cell invasiveness that was suppressed
      by inhibitors of protein kinase C (PKC) or of PKC-zeta, specifically. Finally,
      focal induction of Pten deficiency in vivo promoted angiogenesis in affected
      brains. Thus, we show that Pten deficiency in pRb-deficient astrocytoma cells
      contributes to tumor progression via multiple mechanisms, including suppression
      of apoptosis, increased cell invasion, and angiogenesis, all of which are
      hallmarks of high-grade astrocytoma. These studies not only provide mechanistic
      insight into the role of Pten in astrocytoma suppression but also describe a
      valuable animal model for preclinical testing that is coupled with a primary cell
      based system for target discovery and drug screening.

PMID- 15958562
TI  - Loss of the forkhead transcription factor FoxM1 causes centrosome amplification
      and mitotic catastrophe.
AB  - Expression of the forkhead transcription factor FoxM1 correlates with
      proliferative status in a variety of normal and transformed cell types. Elevated
      expression of FoxM1 has been noted in both hepatocellular carcinoma and basal
      cell carcinoma. However, whether FoxM1 expression is essential for the viability
      of transformed cells is unknown. We report here that the expression of FoxM1 is
      significantly elevated in primary breast cancer. Microarray analysis shows that
      FoxM1 regulates genes that are essential for faithful chromosome segregation and
      mitosis, including Nek2, KIF20A, and CENP-A. Loss of FoxM1 expression generates
      mitotic spindle defects, delays cells in mitosis, and induces mitotic
      catastrophe. Time-lapse microscopy indicates that depletion of FoxM1 generates
      cells that enter mitosis but are unable to complete cell division, resulting in
      either mitotic catastrophe or endoreduplication. These findings indicate that
      FoxM1 depletion causes cell death due to mitotic catastrophe and that inhibiting
      FoxM1 represents a therapeutic strategy to target breast cancer.

PMID- 15958563
TI  - Cathepsin D is a potential serum marker for poor prognosis in glioma patients.
AB  - Cathepsin D is an aspartyl protease involved in protein catabolism and tissue
      remodeling which can be secreted from cancer cells. To identify a potential serum
      marker for gliomas, we investigated the gene expression levels of cathepsin D in
      87 tissue samples and measured the protein concentrations in sera of glioma
      patients. The tissue samples consisted of 43 glioblastomas, 13 anaplastic
      astrocytomas, 22 astrocytomas, and 9 normal brain tissues. The results of real
      time quantitative reverse transcription-PCR analysis showed that cathepsin D
      transcript levels became significantly higher as the glioma grade advanced (P =
      0.0466, glioblastoma and anaplastic astrocytoma; P = 0.0008, glioblastoma and
      astrocytoma; P = 0.0271, glioblastoma and normal brain tissue; unpaired t test).
      Immunohistochemical analysis with anti-cathepsin D antibody revealed dense and
      spotty staining in the tumor cells with high transcript levels. The low
      expression of cathepsin D significantly correlated with long survival of the
      glioma patients. Furthermore, the glioblastoma patients with high gene expression
      of cathepsin D lived significantly shorter than those with low expression (P =
      0.0104, Cox-Mantel log-rank test) and frequently had leptomeningeal dissemination
      (P = 0.0016, chi2 test). The multivariate analysis confirmed that the cathepsin D
      expression level was an independent predictor for short survival (P = 0.0102, Cox
      proportional hazard regression model). Measurement of the serum cathepsin D
      concentrations by ELISA showed a significant increase in the patients with high
      grade gliomas as compared with the low-grade tumors (P = 0.0081, chi2 test).
      These results collectively suggest that cathepsin D could be a potential serum
      marker for the prediction of aggressive nature of human gliomas.

PMID- 15958564
TI  - Tumor-associated NH2-terminal fragments are the most stable part of the
      adenomatous polyposis coli protein and can be regulated by interactions with COOH
      terminal domains.
AB  - Truncation mutations in the adenomatous polyposis coli (APC) gene are responsible
      for familial and sporadic colorectal cancer. APC is a large, multifunctional
      protein involved in cell migration, proliferation, and differentiation. Dominant
      effects that have been attributed to the NH2-terminal fragments of APC expressed
      in tumors may result from loss of functions due to lack of COOH-terminal regions
      or gain of functions due to fewer regulatory interactions. Resolving this issue
      and determining how structural changes contribute to the multiple functions of
      the APC protein requires knowledge about the structural organization of the APC
      molecule. To this end, we used limited proteolysis to distinguish regions of the
      molecule with limited structure from those that form well-folded domains. We
      discovered that the NH2-terminal region of APC was most resistant to proteolytic
      degradation, whereas middle and COOH-terminal regions were significantly more
      sensitive. Binding of APC to microtubules protected COOH-terminal regions of APC
      against proteolysis, consistent with the idea that this region of the molecule
      becomes ordered when bound to microtubules. Furthermore, interactions between the
      NH2- and COOH-terminal domains of APC were identified in vitro and in vivo,
      suggesting that NH2-terminal fragments of APC may be regulated by interactions
      with COOH-terminal domains. Indeed, expressing COOH-terminal APC fragments in
      tumor cells resulted in changes in the protein interactions of endogenous NH2
      terminal fragments in these cells. Thus, the dominant function of NH2-terminal
      APC fragments found in tumor cells could be explained by loss of this regulation
      in tumors where COOH-terminal domains are missing.

PMID- 15958565
TI  - A novel function for galectin-7: promoting tumorigenesis by up-regulating MMP-9
      gene expression.
AB  - Metastasis is a multistep process by which cancer cells, after acquiring several
      capabilities, spread to distinct sites in the body. It is the major cause of
      death in individuals suffering from cancer. We have recently identified galectin
      7 as a new gene associated with the progression of T cell lymphoma toward a
      metastatic phenotype, suggesting a possible causal relationship. The present
      study was designed to investigate the role of galectin-7 in lymphoma. We found
      that the development of thymic lymphoma was accelerated when induced by lymphoma
      cells overexpressing galectin-7. Moreover, transfection of an expression vector
      containing the galectin-7 gene in low metastatic lymphoma cells increased their
      metastatic behavior and confers these cells with the new ability to overcome the
      resistance of intercellular adhesion molecule-1-deficient mice to lymphoma
      dissemination. Finally, we provide data suggesting that galectin-7 modulates the
      aggressive behavior of lymphoma cells by controlling the expression of metastatic
      genes, such as MMP-9. This hypothesis is based on the following evidence: (a)
      galectin-7 transfectants have higher levels of MMP-9 expression, (b) addition of
      beta-lactose completely inhibits expression of MMP-9 by galectin-7 transfectants,
      and (c) recombinant forms of galectin-7 induces the expression of MMP-9 in both
      mouse and human lymphoma cells. Our results have uncovered the existence of a
      previously undescribed activity, the promotion of cancer cell malignancy, to
      galectin-7.

PMID- 15958566
TI  - Tumor cyclooxygenase-2/prostaglandin E2-dependent promotion of FOXP3 expression
      and CD4+ CD25+ T regulatory cell activities in lung cancer.
AB  - Cyclooxygenase (COX)-2 and its product prostaglandin (PG) E2 underlie an
      immunosuppressive network that is important in the pathogenesis of non-small cell
      lung cancer. CD4+ CD25+ T regulatory (Treg) cells play an important role in
      maintenance of immunologic self-tolerance. CD4+ CD25+ Treg cell activities
      increase in lung cancer and appear to play a role in suppressing antitumor immune
      responses. Definition of the pathways controlling Treg cell activities will
      enhance our understanding of limitation of the host antitumor immune responses.
      Tumor-derived COX-2/PGE2 induced expression of the Treg cell-specific
      transcription factor, Foxp3, and increased Treg cell activity. Assessment of E
      prostanoid (EP) receptor requirements revealed that PGE2-mediated induction of
      Treg cell Foxp3 gene expression was significantly reduced in the absence of the
      EP4 receptor and ablated in the absence of the EP2 receptor expression. In vivo,
      COX-2 inhibition reduced Treg cell frequency and activity, attenuated Foxp3
      expression in tumor-infiltrating lymphocytes, and decreased tumor burden.
      Transfer of Treg cells or administration of PGE2 to mice receiving COX-2
      inhibitors reversed these effects. We conclude that inhibition of COX-2/PGE2
      suppresses Treg cell activity and enhances antitumor responses.

PMID- 15958567
TI  - Silencing of epidermal growth factor receptor suppresses hypoxia-inducible factor
      2-driven VHL-/- renal cancer.
AB  - Inactivating mutations in the von Hippel-Lindau (VHL) tumor suppressor gene are
      associated with clear cell renal cell carcinoma (VHL-/- RCC), the most frequent
      malignancy of the human kidney. The VHL protein targets the alpha subunits of
      hypoxia-inducible factor (HIF) transcription factor for ubiquitination and
      degradation. VHL-/- RCC cells fail to degrade HIF resulting in the constitutive
      activation of its target genes, a process that is required for tumorigenesis. We
      recently reported that HIF activates the transforming growth factor
      alpha/epidermal growth factor receptor (TGF-alpha/EGFR) pathway in VHL-defective
      RCC cells. Here, we show that short hairpin RNA (shRNA)-mediated inhibition of
      EGFR is sufficient to abolish HIF-dependent tumorigenesis in multiple VHL-/- RCC
      cell lines. The 2alpha form of HIF (HIF-2alpha), but not HIF-1alpha, drives in
      vitro and in vivo tumorigenesis of VHL-/- RCC cells by specifically activating
      the TGF-alpha/EGFR pathway. Transient incubation of VHL-/- RCC cell lines with
      small interfering RNA directed against EGFR prevents autonomous growth in two
      dimensional culture as well as the ability of these cells to form dense spheroids
      in a three-dimensional in vitro tumor assay. Stable expression of shRNA against
      EGFR does not alter characteristics associated with VHL loss including
      constitutive production of HIF targets and defects in fibronectin deposition. In
      spite of this, silencing of EGFR efficiently abolishes in vivo tumor growth of
      VHL loss RCC cells. These data identify EGFR as a critical determinant of HIF
      2alpha-dependent tumorigenesis and show at the molecular level that EGFR remains
      a credible target for therapeutic strategies against VHL-/- renal carcinoma.

PMID- 15958568
TI  - Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation
      of liver metastases in preclinical models.
AB  - Liver metastasis is a clinically significant contributor to the mortality
      associated with melanoma, colon, and breast cancer. Preclinical mouse models are
      essential to the study of liver metastasis, yet their utility has been limited by
      the inability to study this dynamic process in a noninvasive and longitudinal
      manner. This study shows that three-dimensional high-frequency ultrasound can be
      used to noninvasively track the growth of liver metastases and evaluate potential
      chemotherapeutics in experimental liver metastasis models. Liver metastases
      produced by mesenteric vein injection of B16F1 (murine melanoma), PAP2 (murine H
      ras-transformed fibroblast), HT-29 (human colon carcinoma), and MDA-MB-435/HAL
      (human breast carcinoma) cells were identified and tracked longitudinally. Tumor
      size and location were verified by histologic evaluation. Tumor volumes were
      calculated from the three-dimensional volumetric data, with individual liver
      metastases showing exponential growth. The importance of volumetric imaging to
      reduce uncertainty in tumor volume measurement was shown by comparing three
      dimensional segmented volumes with volumes estimated from diameter measurements
      and the assumption of an ellipsoid shape. The utility of high-frequency
      ultrasound imaging in the evaluation of therapeutic interventions was established
      with a doxorubicin treatment trial. These results show that three-dimensional
      high-frequency ultrasound imaging may be particularly well suited for the
      quantitative assessment of metastatic progression and the evaluation of
      chemotherapeutics in preclinical liver metastasis models.

PMID- 15958569
TI  - Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and
      cytolytic activity of natural killer cells.
AB  - Detergent-soluble membrane vesicles are actively released by human pancreas (Colo
      /Colo+) and colon (CX-/CX+) carcinoma sublines, differing in their capacity to
      present heat shock protein 70 (Hsp70)/Bag-4 on their plasma membranes. Floating
      properties, acetylcholine esterase activity, and protein composition
      characterized them as exosomes. An enrichment of Rab-4 documented their
      intracellular transport route from early endosomes to the plasma membrane. After
      solubilization, comparable amounts of cytosolic proteins, including tubulin,
      Hsp70, Hsc70, and Bag-4, but not ER-residing Grp94 and calnexin, were detectable
      in tumor-derived exosomes. However, with respect to the exosomal surface, only
      Colo+/CX+ but not Colo-/CX- derived exosomes were Hsp70 membrane positive.
      Therefore, concomitant with an up-regulated cell surface density of activation
      markers, migration and Hsp70 reactivity of natural killer (NK) cells was
      stimulated selectively by Hsp70/Bag-4 surface-positive exosomes, but not by their
      negative counterparts and tumor cell lysates. Moreover, the exosome-mediated
      lytic activity of NK cells was blockable by Hsp70-specific antibody. As already
      shown for TKD stimulation, NK cells preincubated with Hsp70 surface-positive
      exosomes initiated apoptosis in tumors through granzyme B release. In summary,
      our data provide an explanation how Hsp70 reactivity in NK cells is induced by
      tumor-derived exosomes.

PMID- 15958570
TI  - Sensitization of glioma cells to Fas-dependent apoptosis by chemotherapy-induced
      oxidative stress.
AB  - A prominent feature of glioblastoma is its resistance to death from Fas pathway
      activation. In this study, we explored the modulation of Fas-induced glioblastoma
      death with chemotherapeutic agents. Camptothecin significantly increased the
      glioblastoma cell death response to Fas receptor activation regardless of p53
      status. Sublethal concentrations of camptothecin reduced the IC50 of agonistic
      anti-Fas antibody (CH-11) 10-fold, from 500 to 50 ng/mL, in human U87
      glioblastoma cells (p53 wild-type). Cell viability in response to camptothecin,
      CH-11 alone, and the combination of camptothecin + CH-11 was found to be 84%,
      85%, and 47% (P < 0.001), respectively. A similar pattern of relative
      cytotoxicity was found in U373 cells (p53 mutant). We further examined the
      pathways and mechanisms involved in this apparent synergistic cytotoxic response.
      Cell death was found to be predominantly apoptotic involving both extrinsic and
      intrinsic pathways as evidenced by annexin V staining, cleavage of caspases (3,
      8, and 9), increased caspase activities, Smac release, and cytoprotection by
      caspase inhibitors. Expression of Fas-associated death domain, and not Fas, Fas
      ligand, or caspase proteins, increased following cell treatment with camptothecin
      + CH-11. Camptothecin treatment enhanced c-jun-NH2-kinase activation in response
      to CH-11, but inhibition of c-jun-NH2-kinase did not prevent cell death induced
      by the combination treatment. Reactive oxygen species, especially H2O2, were
      elevated following camptothecin treatment; and H2O2 enhanced cell death induced
      by CH-11. The antioxidants glutathione and N-acetyl-cysteine prevented cell death
      induced by camptothecin + CH-11. These findings show that camptothecin synergizes
      with Fas activation to induce glioblastoma apoptosis via a mechanism involving
      reactive oxygen species and oxidative stress pathways.

PMID- 15958571
TI  - SV40-dependent AKT activity drives mesothelial cell transformation after asbestos
      exposure.
AB  - Human malignant mesothelioma is an aggressive cancer generally associated with
      exposure to asbestos, although SV40 virus has been involved as a possible
      cofactor by a number of studies. Asbestos fibers induce cytotoxicity in human
      mesothelial cells (HMC), although cell survival activated by key signaling
      pathways may promote transformation. We and others previously reported that SV40
      large T antigen induces autocrine loops in HMC and malignant mesothelioma cells,
      leading to activation of growth factor receptors. Now we show that SV40 induces
      cell survival via Akt activation in malignant mesothelioma and HMC cells exposed
      to asbestos. Consequently, prolonged exposure to asbestos fibers progressively
      induces transformation of SV40-positive HMC. As a model of SV40/asbestos
      cocarcinogenesis, we propose that malignant mesothelioma originates from a
      subpopulation of transformed stem cells and that Akt signaling is a novel
      therapeutic target to overcome malignant mesothelioma resistance to conventional
      therapies.

PMID- 15958572
TI  - A human- and male-specific protocadherin that acts through the wnt signaling
      pathway to induce neuroendocrine transdifferentiation of prostate cancer cells.
AB  - Protocadherin-PC (PCDH-PC) is a gene on the human Y chromosome that is
      selectively expressed in apoptosis- and hormone-resistant human prostate cancer
      cells. The protein encoded by PCDH-PC is cytoplasmically localized and has a
      small serine-rich domain in its COOH terminus that is homologous to the beta
      catenin binding site of classical cadherins. Variants of prostate cancer cells
      that express PCDH-PC have high levels of nuclear beta-catenin protein and
      increased wnt-signaling. In this study, we show that transfection of human
      prostate cancer cells (LNCaP) with PCDH-PC or culture of these cells in androgen
      free medium (a condition that up-regulates PCDH-PC expression) activates wnt
      signaling as assessed by nuclear accumulation of beta-catenin, increased
      expression of luciferase from a reporter vector promoted by Tcf binding elements
      and increased expression of wnt target genes. Moreover, LNCaP cells transfected
      with PCDH-PC or grown in androgen-free medium transdifferentiate to
      neuroendocrine-like cells marked by elevated expression of neuron-specific
      enolase and chromogranin-A. Neuroendocrine transdifferentiation was also observed
      when LNCaP cells were transfected by stabilized beta-catenin. Increased wnt
      signaling and neuroendocrine transdifferentiation of LNCaP cells induced by
      culture in androgen-free medium was suppressed by short interfering RNAs that
      target PCDH-PC as well as by dominant-negative Tcf or short interfering RNA
      against beta-catenin, supporting the hypothesis that increased expression of PCDH
      PC is driving neuroendocrine transdifferentiation by activating wnt signaling.
      These findings have significant implications for the process through which
      prostate cancers progress to hormone resistance in humans.

PMID- 15958573
TI  - 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone from cigarette smoke stimulates
      colon cancer growth via beta-adrenoceptors.
AB  - Cigarette smoking is a risk factor for colorectal cancer. It is suggested that 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific
      nitrosamine, mediates the carcinogenic action of cigarette smoking by promoting
      cancer growth. In the present study, the proliferative response of a cultured
      colon cancer cell line HT-29 to NNK was determined. It was found that NNK dose
      dependently stimulated HT-29 cell proliferation. In this regard, the stimulatory
      action of NNK was abolished by atenolol and ICI 118,551, a beta1- and beta2
      selective antagonist, respectively. In addition, cell growth was stimulated by
      the nonselective adrenergic agonist, noradrenaline, and more effectively by the
      beta-selective agonist, isoproterenol. The second message cyclic AMP level for
      beta-adrenoceptor activation was elevated by isoproterenol and NNK treatment.
      These agents also up-regulated cyclooxygenase-2 expression, cytosolic
      phospholipase A2 expression, and prostaglandin E2 release. Beta2-adrenoceptor
      blockade with ICI 118,551, in contrast, significantly decreased cyclooxygenase-2
      expression, cytosolic phospholipase A2 expression and prostaglandin E2 release
      induced by NNK and isoproterenol. To conclude, it is proposed that NNK stimulates
      HT-29 cell proliferation through beta-adrenoceptors, preferentially beta2
      receptors. Activation of the beta-adrenoceptors, and the consequent cyclic AMP
      elevation coupled with the downstream arachidonic acid pathway, is perhaps an
      important mechanistic cascade in the promotion of colon cancer growth. These
      findings partly elucidate the carcinogenic actions of cigarette smoke and shed
      new light on the novel modulatory role of beta-adrenoceptors in the development
      of colon cancer.

PMID- 15958574
TI  - Macrophages promote the invasion of breast carcinoma cells via a colony
      stimulating factor-1/epidermal growth factor paracrine loop.
AB  - Previous studies have shown that macrophages and tumor cells are comigratory in
      mammary tumors and that these cell types are mutually dependent for invasion.
      Here we show that macrophages and tumor cells are necessary and sufficient for
      comigration and invasion into collagen I and that this process involves a
      paracrine loop. Macrophages express epidermal growth factor (EGF), which promotes
      the formation of elongated protrusions and cell invasion by carcinoma cells.
      Colony stimulating factor 1 (CSF-1) produced by carcinoma cells promotes the
      expression of EGF by macrophages. In addition, EGF promotes the expression of CSF
      1 by carcinoma cells thereby generating a positive feedback loop. Disruption of
      this loop by blockade of either EGF receptor or CSF-1 receptor signaling is
      sufficient to inhibit both macrophage and tumor cell migration and invasion.

PMID- 15958575
TI  - Survivin-responsive conditionally replicating adenovirus exhibits cancer-specific
      and efficient viral replication.
AB  - Although a conditionally replicating adenovirus (CRA) exhibiting cancer-selective
      replication and induction of cell death is an innovative potential anticancer
      agent, current imperfections in cancer specificity and efficient viral
      replication limit the usefulness of this technique. Here, we constructed survivin
      responsive CRAs (Surv.CRAs), in which expression of the wild-type or mutant
      adenoviral early region 1A (E1A) gene is regulated by the promoter of survivin, a
      new member of the inhibitor of apoptosis gene family. We explored the cancer
      specificity and effectiveness of viral replication of Surv.CRAs, evaluating their
      potential as a treatment for cancer. The survivin promoter was strongly activated
      in all cancers examined at levels similar to or even higher than those seen for
      representative strong promoters; in contrast, low activity was observed in normal
      cells. Surv.CRAs efficiently replicated and potently induced cell death in most
      types of cancer. In contrast, minimal viral replication in normal cells did not
      induce any detectable cytotoxicity. A single injection of Surv.CRAs into a
      preestablished tumor expressing survivin, even at relatively low levels, induced
      significant tumor death and inhibition of tumor growth. Furthermore, Surv.CRAs
      were superior to telomerase-dependent CRAs, one of the most effective CRAs that
      have been examined to date, both in terms of cancer specificity and efficiency.
      Thus, Surv.CRAs are an attractive potential anticancer agent that could
      effectively and specifically treat a variety of cancers.

PMID- 15958576
TI  - Targeted measles virus vector displaying echistatin infects endothelial cells via
      alpha(v)beta3 and leads to tumor regression.
AB  - Targeting tumor-associated vascular endothelium by replication-competent viral
      vectors is a promising strategy for cancer gene therapy. Here we describe the
      development of a viral vector based on the Edmonston vaccine strain of measles
      virus targeted to integrin alpha(v)beta3, which is expressed abundantly on
      activated but not quiescent vascular endothelium. We displayed a disintegrin,
      M28L echistatin that binds with a high affinity to integrin alpha(v)beta3 on the
      COOH terminus of the viral attachment (H) protein and rescued the replication
      competent recombinant virus by reverse genetics. The new targeted virus was named
      measles virus echistatin vector (MV-ERV). Its native binding to CD46 was
      purposefully retained to allow virus infection of tumor cells expressing this
      receptor. MV-ERV correctly displayed echistatin on the outer surface of its
      envelope and produced interesting ring formation phenomena due to cell detachment
      upon infection of susceptible Vero cells in vitro. MV-ERV grew to 10(6) plaque
      forming units/mL, slightly lower than the parental Edmonston strain of measles
      virus (MV-Edm), but it selectively infected Chinese hamster ovary cells
      expressing integrin alpha(v)beta3. It also selectively infected both bovine and
      human endothelial cells on matrigels and unlike MV-Edm, MV-ERV infected newly
      formed blood vessels in chorioallantoic membrane assays. In animal models, MV-ERV
      but not the control MV-Edm caused the regression of s.c. xenografts of resistant
      multiple myeloma tumors (MM1) in severe combined immunodeficient mice. The tumors
      were either completely eradicated or their growth was significantly retarded. The
      specificity, potency, and feasibility of MV-ERV infection clearly show the
      potential use of MV-ERV in gene therapy for targeting tumor-associated
      vasculature for the treatment of solid tumors.

PMID- 15958577
TI  - Expression of Siva-1 protein or its putative amphipathic helical region enhances
      cisplatin-induced apoptosis in breast cancer cells: effect of elevated levels of
      BCL-2.
AB  - cis-Diaminedichloroplatinum (II) (cisplatin) is routinely used to treat various
      types of cancers; however, a significant number develop resistance. One of the
      underlying factors that contribute to cisplatin resistance is the elevated level
      of BCL-2 and/or BCL-XL, which promotes cell survival. A potential method of
      overcoming such resistance is to use a potentiator that is capable of
      neutralizing the antiapoptotic effects of BCL-2/BCL-XL, such as Siva-1. We
      previously cloned the proapoptotic protein Siva-1 and showed a possible role for
      it in both extrinsic and intrinsic apoptosis. Using an adenovirus-based
      expression system, we now show that Siva-1 can synergize with cisplatin in
      inducing apoptosis in MCF7 and MDA-MB-231 breast cancer cells. In an anchorage
      independent clonogenicity assay, MCF7/caspase-3 cells stably expressing Siva-1,
      but not the control cells, showed a dramatic decrease in the number of colonies
      formed on one-time cisplatin treatment. Further, we show that the unique putative
      amphipathic helical region (SAH) in Siva-1 (amino acid residues 36-55) is
      necessary and sufficient for the observed enhancement in cisplatin-induced
      apoptosis by Siva-1. Although cisplatin treatment results in significant
      elevation in the expression of Fas ligand and intracellular p21 levels,
      expression of Siva-1 has no additional benefit. Instead, the enhancement in
      apoptosis seems to be due to activation of intrinsic pathway that involves
      caspase-9 activation. Moreover, Siva-1 augments cisplatin-mediated cell death in
      MCF7 cells stably expressing BCL-2. We therefore propose that Siva-1 or its SAH
      region can be used as a potentiator of cisplatin-based chemotherapy.

PMID- 15958578
TI  - Inhibition of DNA repair by a herpes simplex virus vector enhances the
      radiosensitivity of human glioblastoma cells.
AB  - Expression of the herpes simplex virus (HSV) protein, ICP0, from the viral
      genome, rendered two radioresistant human glioblastoma multiforme cell lines more
      sensitive to the effects of ionizing radiation. Using the 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazolium bromide and clonogenic survival assays, U87-MG and
      T98 cell survival was more greatly decreased as a function of ionizing radiation
      dose when ICP0 was preexpressed in cells compared with when ICP0 was not
      expressed. Consistent with previous results, we found that the catalytic subunit
      of DNA-dependent protein kinase was degraded as a function of ICP0 in both cell
      types. This most likely resulted in the inhibition of DNA repair as inferred by
      the persistence of gammaH2AX foci or DNA double-strand breaks. Enhanced apoptosis
      was also found to occur following irradiation of U87-MG cells preinfected with
      the ICP0-producing HSV-1 mutant, d106. Our results suggest that expression of
      ICP0 in human glioblastoma multiforme cells inhibits the repair of DNA double
      strand breaks after ionizing radiation treatment, decreasing the survival of
      these cells in part by induction of apoptosis.

PMID- 15958579
TI  - Nanoparticle targeting of anticancer drug improves therapeutic response in animal
      model of human epithelial cancer.
AB  - Prior studies suggested that nanoparticle drug delivery might improve the
      therapeutic response to anticancer drugs and allow the simultaneous monitoring of
      drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in
      diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a
      targeting agent and then coupled to either methotrexate or tritium and either
      fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v.
      into immunodeficient mice bearing human KB tumors that overexpress the folic acid
      receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles
      concentrated in the tumor and liver tissue over 4 days after administration. The
      tumor tissue localization of the folate-targeted polymer could be attenuated by
      prior i.v. injection of free folic acid. Confocal microscopy confirmed the
      internalization of the drug conjugates into the tumor cells. Targeting
      methotrexate increased its antitumor activity and markedly decreased its
      toxicity, allowing therapeutic responses not possible with a free drug.

PMID- 15958580
TI  - Antitumor activity of rapamycin in a transgenic mouse model of ErbB2-dependent
      human breast cancer.
AB  - The ErbB2 (Neu) receptor tyrosine kinase is frequently overexpressed in human
      breast cancers, and this phenotype correlates with a poor clinical prognosis. We
      examined the effects of the mammalian target of rapamycin inhibitor, rapamycin,
      on mammary tumorigenesis in transgenic mice bearing an activated ErbB2 (NeuYD)
      transgene in the absence or presence of a second transgene encoding vascular
      endothelial growth factor (VEGF). Treatment of NeuYD or NeuYD x VEGF mice with
      rapamycin dramatically inhibited tumor growth accompanied by a marked decrease in
      tumor vascularization. Two key events that may underlie the antitumor activity of
      rapamycin were decreased expression of ErbB3 and inhibition of hypoxia-inducible
      factor-1-dependent responses to hypoxic stress. Rapamycin exposure caused only a
      modest inhibition of the proliferation of tumor-derived cell lines in standard
      monolayer cultures, but dramatically inhibited the growth of the same cells in
      three-dimensional cultures, due in part to the induction of apoptotic cell death.
      These studies underscore the therapeutic potential of mammalian target of
      rapamycin inhibitors in ErbB2-positive breast cancers and indicate that, relative
      to monolayer cultures, three-dimensional cell cultures are more predictive in
      vitro models for studies of the antitumor mechanisms of rapamycin and related
      compounds.

PMID- 15958581
TI  - DNA-protein cross-links and replication-dependent histone H2AX phosphorylation
      induced by aminoflavone (NSC 686288), a novel anticancer agent active against
      human breast cancer cells.
AB  - Aminoflavone (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4
      one) (NSC 686288) is a candidate for possible advancement to phase I clinical
      trial. Aminoflavone has a unique activity profile in the NCI 60 cell lines
      (COMPARE analysis; http://www.dtp.nci.nih.gov/docs/dtp_search.html), and exhibits
      potent cellular and animal antitumor activity. To elucidate the mechanism of
      action of aminoflavone, we studied DNA damage in MCF-7 cells. Aminoflavone
      induced DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB).
      Aminoflavone induced high levels of DPC and much lower level of SSB than
      camptothecin, which induces equal levels of DPC and SSB due to the trapping
      topoisomerase I-DNA complexes. Accordingly, neither topoisomerase I nor
      topoisomerase II were detectable in the aminoflavone-induced DPC. Aminoflavone
      also induced dose- and time-dependent histone H2AX phosphorylation (gamma-H2AX).
      Gamma-H2AX foci occurred with DPC formation, and like DPC, persisted after
      aminoflavone removal. Aphidicolin prevented gamma-H2AX formation, suggesting that
      gamma-H2AX foci correspond to replication-associated DNA double-strand breaks.
      Accordingly, no gamma-H2AX foci were found in proliferating cell nuclear antigen
      negative or in mitotic cells. Bromodeoxyuridine incorporation and fluorescence
      activated cell sorting analyses showed DNA synthesis inhibition uniformly
      throughout the S phase after exposure to aminoflavone. Aminoflavone also induced
      RPA2 and p53 phosphorylation, and induced p21(Waf1/Cip1) and MDM2, demonstrating
      S-phase checkpoint activation. These studies suggest that aminoflavone produces
      replication-dependent DNA lesions and S-phase checkpoint activation following DPC
      formation. Gamma-H2AX may be a useful clinical marker for monitoring the efficacy
      of aminoflavone in tumor therapies.

PMID- 15958582
TI  - The antitumor enediyne C-1027 alters cell cycle progression and induces
      chromosomal aberrations and telomere dysfunction.
AB  - This study examined the extent of chromosome instability induced in cultured
      human colon carcinoma HCT116 cells by the antitumor radiomimetic enediyne
      antibiotic C-1027. Spectral karyotype analysis showed frequent intrachromosomal
      fusions and fragmentations 26 hours after addition of as little as 0.035 nmol/L C
      1027. When the concentration was increased to 0.14 nmol/L C-1027, 92% of cells
      showed chromosomal aberrations compared with only 2.9% after treatment with an
      equivalent growth inhibitory dose of ionizing radiation (20 Gy). Thus, chromosome
      misrejoining was associated to a much greater extent with C-1027-induced than
      with ionizing radiation-induced cell growth inhibition. Despite these
      aberrations, a large fraction of C-1027-treated cells progressed into G1. Comet
      analysis showed that these extensive chromosomal anomalies were not due to
      increased induction or reduced repair of C-1027-induced compared with ionizing
      radiation-induced strand breaks. Fluorescence in situ hybridization analysis
      showed that misrejoining of telomere repeats (i.e., chromosomes joined end to end
      at their telomeres or fused together after complete loss of telomere sequences)
      was observed within 26 hours of C-1027 addition. The extreme cytotoxicity of C
      1027 may reflect both induction and erroneous repair of DNA double-strand break
      in the whole genome and/or in subgenomic targets such as telomere sequences.

PMID- 15958583
TI  - Nestin-linked green fluorescent protein transgenic nude mouse for imaging human
      tumor angiogenesis.
AB  - We report here a novel transgenic nude mouse for the visualization of human tumor
      angiogenesis. We have recently shown that the neural stem cell marker nestin is
      expressed in hair follicle stem cells and blood vessel networks in the skin of
      C57/B6 transgenic mice with nestin regulatory element-driven green fluorescent
      protein (ND-GFP). Others have shown ND-GFP is expressed in the brain, pancreas,
      and testes in these mice. In the present study, the nestin ND-GFP gene was
      crossed into nude mice on the C57/B6 background to obtain ND-GFP nude mice. ND
      GFP was expressed in the brain, spinal cord, pancreas, stomach, esophagus, heart,
      lung, blood vessels of glomeruli, blood vessels of skeletal muscle, testes, hair
      follicles, and blood vessel network in the skin of ND-GFP nude mice. Human lung
      cancer, pancreatic cancer, and colon cancer cell lines as well as a murine
      melanoma cell line and breast cancer tumor cell line expressing red fluorescent
      protein were implanted orthotopically, and a red fluorescent protein-expressing
      human fibrosarcoma was implanted s.c. in the ND-GFP nude mice. These tumors grew
      extensively in the ND-GFP mice. ND-GFP was highly expressed in proliferating
      endothelial cells and nascent blood vessels in the growing tumors, visualized by
      dual-color fluorescence imaging. Results of immunohistochemical staining showed
      that CD31 was expressed in the ND-GFP-expressing nascent blood vessels. The ND
      GFP transgenic nude mouse model enables the visualization of nascent angiogenesis
      in human and mouse tumor progression. These results suggest that this model is
      useful for the imaging of the angiogenesis of human as well as rodent tumors and
      visualization of the efficacy of angiogenetic inhibitors.

PMID- 15958584
TI  - SKI-606, a Src/Abl inhibitor with in vivo activity in colon tumor xenograft
      models.
AB  - Src up-regulation is a common event in human cancers. In colorectal cancer,
      increased Src levels are an indicator of poor prognosis, and progression to
      metastatic disease is associated with substantial increases in Src activity.
      Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl
      kinases, against colon tumor lines in vitro and in s.c. tumor xenograft models.
      SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25
      micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a
      Src substrate, was reduced by similar concentrations of inhibitor.
      Antiproliferative activity on plastic did not correlate with Src inhibition in
      either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively),
      although submicromolar concentrations of SKI-606 inhibited HT29 cell colony
      formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids
      to condense into compact spheroids. On oral administration to nude mice at the
      lowest efficacious dose, peak plasma concentrations of approximately 3
      micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were
      observed. SKI-606 was orally active in s.c. colon tumor xenograft models and
      caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and
      Colo205 tumors. SKI-606 inhibited HT29 tumor growth on once daily administration,
      whereas twice daily administration was necessary to inhibit Colo205, HCT116, and
      DLD1 tumor growth. These results support development of SKI-606 as a therapeutic
      agent for treatment of colorectal cancer.

PMID- 15958585
TI  - In vitro procoagulant activity induced in endothelial cells by chemotherapy and
      antiangiogenic drug combinations: modulation by lower-dose chemotherapy.
AB  - One of the emerging problems concerning the use of antiangiogenic drugs, when
      used in combination with certain chemotherapy regimens, is enhanced rates and
      severity of adverse clotting events. For as yet unknown reasons, certain drugs
      and particular combinations can induce an elevated incidence of thromboembolic
      events in treated cancer patients [e.g., SU5416, a vascular endothelial cell
      growth factor receptor-2 (VEGFR-2) antagonist, when combined with gemcitabine and
      cisplatin (CDDP)]. Such results highlight the need to develop assays capturing
      the essence of enhanced clot formation under such combination treatment and which
      may have predictive potential as well. Here, we report the possibility of such an
      assay (i.e., the ratio of tissue factor over tissue factor pathway inhibitor
      expression or activity in cultured human endothelial cells calculated as a
      coagulation index). A marked increase in coagulation index was observed after
      exposure to SU5416 and the CDDP/gemcitabine chemotherapy combination in contrast
      to either of these treatments used alone. Substitution of SU5416 with any one of
      ZD6474, SU6668, IMC-1121, a monoclonal antibody to VEGFR-2, or an antibody to
      VEGF (bevacizumab) did not cause a marked increase in the coagulation index, nor
      did the combination of SU5416 with 5-fluorouracil and leucovorin. Finally, we
      noted that reducing the concentrations of gemcitabine and CDDP (i.e., use of
      "metronomic dosing" in vitro) significantly attenuated the coagulation index
      increase induced by these drugs, suggesting that use of low-dose chemotherapy
      regimens might be an approach to consider for reducing the incidence of adverse
      clotting events associated with chemotherapy alone or in conjunction with
      antiangiogenic drug combination therapies.

PMID- 15958586
TI  - Enhanced susceptibility of irradiated tumor vessels to vascular endothelial
      growth factor receptor tyrosine kinase inhibition.
AB  - Previous experiments with PTK787/ZK222584, a specific inhibitor of vascular
      endothelial growth factor receptor (VEGFR) tyrosine kinases, using irradiated
      human FaDu squamous cell carcinoma in nude mice, suggested that radiation-damaged
      tumor vessels are more sensitive to VEGFR inhibition. To test this hypothesis,
      the tumor transplantation site (i.e., the right hind leg of nude mice) was
      irradiated 10 days before transplantation of FaDu to induce radiation damage in
      the host tissue. FaDu tumors vascularized by radiation-damaged blood vessels
      appeared later, grew at a slower rate, and showed more necrosis and a smaller
      vessel area per central tumor section than controls. PTK787/ZK222584 at a daily
      dose of 50 mg/kg body weight had no impact on growth of control tumors. In
      contrast, tumors vascularized by radiation-damaged vessels responded to
      PTK787/ZK222584 with longer latency and slower growth rate than controls, and a
      trend toward further increase in necrosis, indicating that irradiated tumor
      vessels are more susceptible to VEGFR inhibition than unirradiated vessels.
      Although not proving causality, expression analysis of VEGF and VEGFR2 shows that
      enhanced sensitivity of irradiated vessels to a specific inhibitor of VEGFR
      tyrosine kinases correlates with increased expression of the molecular target.

PMID- 15958587
TI  - Activation of mitogen-activated protein kinase in xenografts and cells during
      prolonged treatment with aromatase inhibitor letrozole.
AB  - Ovariectomized mice bearing tumor xenografts grown from aromatase-transfected
      estrogen receptor (ER)-positive human breast cancer cells (MCF-7Ca) were injected
      s.c. with 10 microg/d letrozole for up to 56 weeks. Western blot analysis of the
      tumors revealed that ERs (ERalpha) were increased at 4 weeks but decreased at
      weeks 28 and 56. Expression of erbB-2 and p-Shc increased throughout treatment,
      whereas growth factor receptor binding protein 2 (Grb2) increased only in tumors
      proliferating on letrozole (weeks 28 and 56). In cells isolated from tumors after
      56 weeks and maintained as a cell line (LTLT-Ca) in 1 micromol/L letrozole,
      ERalpha was also decreased whereas erbB-2, adapter proteins (p-Shc and Grb2), and
      the signaling proteins in the mitogen-activated protein kinase (MAPK) cascade
      were increased compared with MCF-7Ca cells. Growth was inhibited in LTLT-Ca cells
      but not in MCF-7Ca cells treated with MAPK kinase 1/2 inhibitors U0126, and
      PD98059 (IC(50) approximately 25 micromol/L). PD98059 (5 micromol/L) also reduced
      MAPK activity and increased ERalpha to the levels in MCF-7Ca cells. Epidermal
      growth factor receptor kinase inhibitor, gefitinib (ZD1839) inhibited growth of
      LTLT-Ca cells (IC(50) approximately 10 micromol/L) and restored their sensitivity
      to tamoxifen and anastrozole. In xenografts, combined treatment with ER down
      regulator fulvestrant and letrozole, prevented increases in erbB-2 and activation
      of MAPK and was highly effective in inhibiting tumor growth throughout 29 weeks
      of treatment. These results indicate that blocking both ER- and growth factor
      mediated transcription resulted in the most effective inhibition of growth of ER
      positive breast cancer cells.

PMID- 15958588
TI  - Potent modulation of intestinal tumorigenesis in Apcmin/+ mice by the polyamine
      catabolic enzyme spermidine/spermine N1-acetyltransferase.
AB  - Intracellular polyamine pools are homeostatically maintained by processes
      involving biosynthesis, catabolism, and transport. Although most polyamine-based
      anticancer strategies target biosynthesis, we recently showed that activation of
      polyamine catabolism at the level of spermidine/spermine N(1)-acetyltransferase-1
      (SSAT) suppresses tumor outgrowth in a mouse prostate cancer model. Herein, we
      examined the effects of differential SSAT expression on intestinal tumorigenesis
      in the Apc(Min/+) (MIN) mouse. When MIN mice were crossed with SSAT-overproducing
      transgenic mice, they developed 3- and 6-fold more adenomas in the small
      intestine and colon, respectively, than normal MIN mice. Despite accumulation of
      the SSAT product, N(1)-acetylspermidine, spermidine and spermine pools were only
      slightly decreased due to a huge compensatory increase in polyamine biosynthetic
      enzyme activities that gave rise to enhanced metabolic flux. When MIN mice were
      crossed with SSAT knock-out mice, they developed 75% fewer adenomas in the small
      intestine, suggesting that under basal conditions, SSAT contributes significantly
      to the MIN phenotype. Despite the loss in catabolic capability, tumor spermidine
      and spermine pools failed to increase significantly due to a compensatory
      decrease in biosynthetic enzyme activity giving rise to a reduced metabolic flux.
      Loss of heterozygosity at the Apc locus was observed in tumors from both SSAT
      transgenic and -deficient MIN mice, indicating that loss of heterozygosity
      remained the predominant oncogenic mechanism. Based on these data, we propose a
      model in which SSAT expression alters flux through the polyamine pathway giving
      rise to metabolic events that promote tumorigenesis. The finding that deletion of
      SSAT reduces tumorigenesis suggests that small-molecule inhibition of the enzyme
      may represent a nontoxic prevention and/or treatment strategy for
      gastrointestinal cancers.

PMID- 15958589
TI  - Seliciclib (CYC202, R-Roscovitine) induces cell death in multiple myeloma cells
      by inhibition of RNA polymerase II-dependent transcription and down-regulation of
      Mcl-1.
AB  - Seliciclib (CYC202, R-roscovitine) is a cyclin-dependent kinase (CDK) inhibitor
      that competes for the ATP binding site on the kinase. It has greatest activity
      against CDK2/cyclin E, CDK7/cyclin H, and CDK9/cyclin T. Seliciclib induces
      apoptosis from all phases of the cell cycle in tumor cell lines, reduces tumor
      growth in xenografts in nude mice and is currently in phase II clinical trials.
      This study investigated the mechanism of cell death in multiple myeloma cells
      treated with seliciclib. In myeloma cells treated in vitro, seliciclib induced
      rapid dephosphorylation of the carboxyl-terminal domain of the large subunit of
      RNA polymerase II. Phosphorylation at these sites is crucial for RNA polymerase
      II-dependent transcription. Inhibition of transcription would be predicted to
      exert its greatest effect on gene products where both mRNA and protein have short
      half-lives, resulting in rapid decline of the protein levels. One such gene
      product is the antiapoptotic factor Mcl-1, crucial for the survival of a range of
      cell types including multiple myeloma. As hypothesized, following the inhibition
      of RNA polymerase II phosphorylation, seliciclib caused rapid Mcl-1 down
      regulation, which preceded the induction of apoptosis. The importance of Mcl-1
      was confirmed by short interfering RNA, demonstrating that reducing Mcl-1 levels
      alone was sufficient to induce apoptosis. These results suggest that seliciclib
      causes myeloma cell death by disrupting the balance between cell survival and
      apoptosis through the inhibition of transcription and down-regulation of Mcl-1.
      This study provides the scientific rationale for the clinical development of
      seliciclib for the treatment of multiple myeloma.

PMID- 15958590
TI  - Calcium/calmodulin-dependent kinase I and calcium/calmodulin-dependent kinase
      kinase participate in the control of cell cycle progression in MCF-7 human breast
      cancer cells.
AB  - Calcium is universally required for cell growth and proliferation. Calmodulin is
      the main intracellular receptor for calcium. Although calcium and calmodulin are
      well known to be required for cell cycle regulation, the target pathways for
      their action remain poorly defined. Potential targets include the
      calcium/calmodulin-dependent kinases (CaM-K). The aim of this study was to
      determine the role of the CaM-Ks on cell proliferation and progress through the
      cell cycle in breast cancer cells. CaM-KI inhibition with either KN-93 or
      specific interfering RNA (siRNA) caused an arrest in the cell cycle in the human
      breast cancer cell line, MCF-7. This arrest occurred in the G(1) phase of the
      cell cycle. Supporting this finding, CaM-K inhibition using KN-93 also resulted
      in a reduction of cyclin D1 protein and pRb phosphorylation when cells were
      compared with control cultures. Furthermore, inhibition of the upstream activator
      of CaM-KI, CaM-KK, using siRNA also resulted in cell cycle arrest. In summary,
      CaM-KK and CaM-KI participate in the control of the G(0)-G(1) restriction check
      point of the cell cycle in human breast cancer cells. This arrest seems due to an
      inhibition in cyclin D1 synthesis and a reduction in pRb phosphorylation. To the
      best of our knowledge, this is the first time that CaM-KK has been reported to be
      involved in mammalian cell cycle regulation and that CaM-Ks are regulating breast
      cancer cell cycle.

PMID- 15958591
TI  - Artificial antigen-presenting cells transduced with telomerase efficiently expand
      epitope-specific, human leukocyte antigen-restricted cytotoxic T cells.
AB  - Human telomerase reverse transcriptase (hTERT) is overexpressed in most human
      tumors, making it a potential target for cancer immunotherapy. hTERT-derived CTL
      epitopes have been identified previously, including p865 (RLVDDFLLV) and p540
      (ILAKFLHWL), which are restricted by the human leukocyte antigen (HLA) class I
      A*0201 allele. However, it remains a major challenge to efficiently and
      consistently expand hTERT-specific CTLs from donor peripheral blood T
      lymphocytes. To bypass the need for generating conventional antigen-presenting
      cells (APC) on an autologous basis, we investigated the potential ability of
      fibroblast-derived artificial APCs (AAPC) to activate and expand HLA-A*0201
      restricted CTLs. We show here that AAPCs stably expressing HLA-A*0201, human
      beta(2)-microglobulin, B7.1, intercellular adhesion molecule-1, and LFA-3,
      together with either p540 and p865 minigenes or the full-length hTERT,
      effectively stimulate tumoricidal, hTERT-specific CTLs. hTERT-expressing AAPCs
      stimulated both p540 and p865 CTLs as shown by peptide-specific cytolysis and
      tetramer staining, indicating that hTERT is processed by the AAPCs and that the
      two peptides are presented as codominant epitopes. The level of cytotoxic
      activity against a panel of tumors comprising hematologic and epithelial
      malignancies varied, correlating overall with the level of HLA-A2 and hTERT
      expression by the target cell. Starting from 100 mL blood, approximately 100
      million hTERT-specific CTLs could be generated over the course of five sequential
      stimulations, representing an expansion of approximately 1 x 10(5). Our data show
      that AAPCs process hTERT antigen and efficiently stimulate hTERT-specific CTLs
      from human peripheral blood T lymphocytes and suggest that sufficient expansion
      could be achieved to be clinically useful for adoptive cell therapy.

PMID- 15958592
TI  - Glioblastomas induce T-lymphocyte death by two distinct pathways involving
      gangliosides and CD70.
AB  - Here we report that glioblastoma multiforme (GBM) mediates immunosuppression by
      promoting T-cell death via tumor-associated CD70 and gangliosides that act
      through receptor-dependent and receptor-independent pathways, respectively. GBM
      lines cocultured with T cells induced lymphocyte death. The GBM lines were
      characterized for their expression of CD70, Fas ligand (FasL), and tumor necrosis
      factor-alpha (TNF-alpha), and the possible participation of those molecules in T
      cell killing was assessed by doing GBM/T cell cocultures in the presence of anti
      CD70 antibodies, Fas fusion proteins, or anti-TNF-alpha antibodies. CD70 but not
      TNF-alpha or FasL is responsible for initiating T-cell death via the receptor
      dependent pathway. Of the four GBM cell lines that induced T-cell death, three
      highly expressed CD70. Two nonapoptogenic GBM lines (CCF3 and U138), on the other
      hand, had only minimally detectable CD70 expression. Blocking experiments with
      the anti-CD70 antibody confirmed that elevated CD70 levels were involved in the
      apoptogenicity of the three GBM lines expressing that molecule. Gangliosides were
      found to participate in the induction of T-cell apoptosis, because the
      glucosylceramide synthase inhibitor (PPPP) significantly reduced the abilities of
      all four apoptogenic lines to kill the lymphocytes. High-performance liquid
      chromatography (HPLC) and mass spectroscopy revealed that GM2, GM2-like
      gangliosides, and GD1a were synthesized in abundance by all four apoptogenic GBM
      lines but not by the two GBMs lacking activity. Furthermore, gangliosides
      isolated from GBM lines as well as HPLC fractions containing GM2 and GD1a were
      directly apoptogenic for T cells. Our results indicate that CD70 and gangliosides
      are both products synthesized by GBMs that may be key mediators of T-cell
      apoptosis and likely contribute to the T-cell dysfunction observed within the
      tumor microenvironment.

PMID- 15958593
TI  - Additive antitumor effect of aromatase inhibitor letrozole and antiestrogen
      fulvestrant in a postmenopausal breast cancer model.
AB  - Blocking estrogen receptors with antiestrogens and blocking estrogen synthesis
      with aromatase inhibitors are two strategies currently being used for reducing
      the effect of estrogen in postmenopausal estrogen receptor-positive breast cancer
      patients. To optimize these treatment strategies, we have investigated whether
      tumor progression can be delayed by combining the pure antiestrogen fulvestrant
      with the nonsteroidal aromatase inhibitor letrozole. These studies were done in
      ovariectomized, athymic mice bearing tumors of estrogen receptor-positive human
      breast cancer cells stably transfected with the aromatase gene (MCF-7Ca). Groups
      of mice with equivalent tumor volumes were injected s.c. daily with vehicle
      (control; n = 6), fulvestrant (1 mg/d; n = 7), letrozole (10 microg/d; n = 18),
      or letrozole (10 microg/d) plus fulvestrant (1 mg/d; n = 5). All treatments were
      effective in suppressing tumor growth compared with controls (P < 0.001). Tumor
      volumes of the fulvestrant-treated group had doubled in 10 weeks. After 19 weeks
      of letrozole (10 microg/d) treatment when tumors had nearly doubled in volume,
      mice (n = 18) were assigned to second-line therapy with letrozole (100 microg/d;
      n = 6), tamoxifen (100 microg/d; n = 6), or remained on letrozole treatment (10
      microg/d; n = 6). However, tumors continued to increase in volume in these
      groups. Tumors of animals treated with the combination of letrozole plus Faslodex
      regressed over 29 weeks of treatment by 45%. Thus, the combination of letrozole
      plus fulvestrant was more effective in suppressing tumor growth than either
      letrozole or fulvestrant alone or sequential therapies with tamoxifen or a higher
      dose of letrozole (100 microg/d).

PMID- 15958594
TI  - The androgen derivative 5alpha-androstane-3beta,17beta-diol inhibits prostate
      cancer cell migration through activation of the estrogen receptor beta subtype.
AB  - Prostate cancer growth depends, in its earlier stages, on androgens and is
      usually pharmacologically modulated with androgen blockade. However, androgen
      ablation therapy may generate androgen-independent prostate cancer, often
      characterized by an increased invasiveness. We have found that the 5alpha-reduced
      testosterone derivative, dihydrotestosterone (the most potent natural androgen)
      inhibits cell migration with an androgen receptor-independent mechanism. We have
      shown that the dihydrotestosterone metabolite 5alpha-androstane-3beta,17beta-diol
      (3beta-Adiol), a steroid which does not bind androgen receptors, but efficiently
      binds the estrogen receptor beta (ERbeta), exerts a potent inhibition of prostate
      cancer cell migration through the activation of the ERbeta signaling. Very
      surprisingly, estradiol is not active, suggesting the existence of different
      pathways for ERbeta activation in prostate cancer cells. Moreover, 3beta-Adiol,
      through ERbeta, induces the expression of E-cadherin, a protein known to be
      capable of blocking metastasis formation in breast and prostate cancer cells. The
      inhibitory effects of 3beta-Adiol on prostate cancer cell migration is
      counteracted by short interfering RNA against E-cadherin. Altogether, the data
      showed that (a) circulating testosterone may act with estrogenic effects
      downstream in the catabolic process present in the prostate, and (b) that the
      estrogenic effect of testosterone derivatives (ERbeta-dependent) results in the
      inhibition of cell migration, although it is apparently different from that
      linked to estradiol on the same receptor and may be protective against prostate
      cancer invasion and metastasis. These results also shed some light on clinical
      observations suggesting that alterations in genes coding for 3beta-hydroxysteroid
      dehydrogenases (the enzymes responsible for 3beta-Adiol formation) are strongly
      correlated with hereditary prostate cancer.

PMID- 15958595
TI  - Inactivation of Myc in murine two-hit B lymphomas causes dormancy with elevated
      levels of interleukin 10 receptor and CD20: implications for adjuvant therapies.
AB  - Overexpression of c-Myc and inactivation of p53 are hallmarks of human Burkitt's
      lymphomas. We had previously showed that transduction of murine p53-null bone
      marrow cells with a Myc-encoding retrovirus is sufficient for B lymphomagenesis.
      To address the role of Myc in tumor sustenance, we generated lymphomas induced by
      the Myc-estrogen receptor fusion protein (MycER). Engrafted hosts were
      continuously treated with the ER ligand 4-hydroxytamoxifen (4-OHT) to allow tumor
      formation. Subsequent inactivation of MycER via 4-OHT deprivation resulted in
      tumor stasis but only partial regression. At the cellular level, dormant
      neoplastic lymphocytes withdrew from mitosis and underwent further B-cell
      differentiation. Concomitantly, they up-regulated genes involved in lymphocyte
      proliferation and survival, most notably interleukin 10 receptor alpha
      (IL10Ralpha) and CD20, the target for antibody therapy with Rituxan. We found
      that overexpression of IL10Ralpha affords significant proliferative advantages
      and in 4-OHT-deprived animals correlates with eventual tumor relapse. Both
      dormant and relapsing tumors maintain IL10Ralpha expression suggesting that they
      might be sensitive to emerging drugs targeting the IL-10 pathway. Up-regulation
      of CD20 following Myc inactivation was also observed in immortalized human
      lymphocytes. Importantly, in this system, Myc(OFF)CD20(HIGH) cells were more
      prone to Rituxan-induced apoptosis than Myc(ON)CD20(MED). Thus, targeting Myc,
      while moderately effective on its own, shapes the phenotype of dormant neoplastic
      cells and sensitizes them to adjuvant molecular therapies.

PMID- 15958596
TI  - Individual variation of somatic gene mutability in relation to cancer
      susceptibility: prospective study on erythrocyte glycophorin a gene mutations of
      atomic bomb survivors.
AB  - It has previously been reported that hemizygous mutant fraction (Mf) at the
      glycophorin A (GPA) locus in erythrocytes increased with radiation dose in
      heterozygotes among Hiroshima and Nagasaki atomic bomb survivors. In the present
      study, we analyzed the relationship between GPA Mf and cancer risk using newly
      developed cancers among previously cancer-free subjects whose GPA Mf had been
      measured between 1988 and 1996. Among 1,723 survivors (1,117 in Hiroshima and 606
      in Nagasaki), we identified 186 subjects who developed a first cancer by the end
      of 2000. We compared the radiation dose responses of GPA Mf between cancer and
      cancer-free groups using a linear-quadratic model fit by multiple regression
      analysis in combination with age, sex, and city. The slope of the GPA Mf dose
      response curve was significantly higher in the cancer group than in the cancer
      free group among Hiroshima subjects. Moreover, no significant difference of GPA
      Mf between cancer and cancer-free groups was found in unexposed controls in the
      two cities. The same conclusions were obtained using a linear dose-response model
      and by further analysis using Cox regression of cancer incidence. These findings
      suggest that there might be interindividual variation in mutability of somatic
      genes and that Hiroshima survivors who have higher mutability in response to
      radiation exposure would be expected to have a higher probability of suffering
      radiation-related cancer.

PMID- 15958597
TI  - Sun exposure, vitamin D receptor gene polymorphisms, and risk of advanced
      prostate cancer.
AB  - Substantial experimental evidence indicates that the hormonal form of vitamin D
      promotes the differentiation and inhibits the proliferation, invasiveness, and
      metastasis of human prostatic cancer cells. Results from epidemiologic studies of
      vitamin D status and/or vitamin D receptor (VDR) polymorphisms and prostate
      cancer risk have been mixed. We conducted a population-based, case-control study
      of advanced prostate cancer among men ages 40 to 79 years from the San Francisco
      Bay area. Interview data on lifetime sun exposure and other risk factors were
      collected for 905 non-Hispanic White men (450 cases and 455 controls). Using a
      reflectometer, we measured constitutive skin pigmentation on the upper underarm
      (a sun-protected site) and facultative pigmentation on the forehead (a sun
      exposed site) and calculated a sun exposure index from these measurements.
      Biospecimens were collected for 426 cases and 440 controls. Genotyping was done
      for VDR polymorphisms in the 5' regulatory region (Cdx-2), exon 2 (FokI), and the
      3' region (TaqI and BglI). Reduced risk of advanced prostate cancer was
      associated with high sun exposure determined by reflectometry [odds ratio (OR),
      0.51; 95% confidence interval (95% CI), 0.33-0.80] and high occupational outdoor
      activity (OR, 0.73; 95% CI, 0.48-1.11). Significant risk reductions with the high
      activity alleles FokI FF or Ff, TaqI tt, and BglI BB genotypes and a
      nonsignificant reduction with Cdx-2 AG or AA genotype were observed in the
      presence of high sun exposure, with ORs ranging from 0.46 to 0.67. Our findings
      support the hypothesis that sun exposure and VDR polymorphisms together play
      important roles in the etiology of prostate cancer.

PMID- 15958598
TI  - Renaming cytokines: MCP-1, major chemokine in pancreatitis.

PMID- 15958599
TI  - Effects of salicylate on plasma membrane mechanics.
AB  - High concentrations of the amphipathic drug salicylate (Sal) block outer hair
      cell (OHC) electromotility resulting in reversible hearing loss. We used optical
      tweezers to study the effects of Sal on the mechanics of the cell plasma
      membrane. Membrane tethers were formed from guinea pig OHCs and cultured human
      embryonic kidney (HEK) cells as controls. HEK cells are commonly used in
      functional expression studies of electromotility. Effective tether viscosity
      (eta(eff)), steady-state tethering force extrapolated to zero pulling rate
      F(ss0), and time constant for tether growth (tau(tg)) were estimated from the
      measurements of the instantaneous tethering force at different tether pulling
      rates. Average values of eta(eff), F(ss0), and tau(tg) for the OHC lateral wall
      plasma membrane and control cell plasma membrane remained the same after Sal
      perfusion, which is consistent with the hypothesis that Sal-induced reversible
      hearing loss appears to be more the result of its competition with essential
      anions and less the result of a change in plasma membrane mechanics.

PMID- 15958600
TI  - Neuronal activity in primate orbitofrontal cortex reflects the value of time.
AB  - Neurons in monkey orbitofrontal cortex (OF) are known to respond to reward
      predicting cues with a strength that depends on the value of the predicted reward
      as determined 1) by intrinsic attributes including size and quality and 2) by
      extrinsic factors including the monkey's state of satiation and awareness of what
      other rewards are currently available. We pose here the question whether another
      extrinsic factor critical to determining reward value-the delay expected to
      elapse before delivery-influences neuronal activity in OF. To answer this
      question, we recorded from OF neurons while monkeys performed a memory-guided
      saccade task in which a cue presented early in each trial predicted whether the
      delay before the monkey could respond and receive a reward of fixed size would be
      short or long. OF neurons tended to fire more strongly in response to a cue
      predicting a short delay. The tendency to fire more strongly in anticipation of a
      short delay was correlated across neurons with the tendency to fire more strongly
      before a large reward. We conclude that neuronal activity in OF represents the
      time-discounted value of the expected reward.

PMID- 15958601
TI  - Relationship of the reserve vesicle population to synaptic depression in the
      tergotrochanteral and dorsal longitudinal muscles of Drosophila.
AB  - We have previously demonstrated that Drosophila synapses possess two vesicle
      populations-a small active zone population replenished by "fast" recycling and a
      much larger reserve population replenished by a slower recycling mechanism that
      includes endosomal intermediates. In this paper, we demonstrate that the synapses
      onto the tergotrochanteral muscle (TTM) are very unusual in that they possess
      only the active zone vesicle population but not the reserve population. The
      depression characteristics to repetitive stimulation of the TTM were compared
      with those of the dorsal longitudinal muscle (DLM), the synapses of which possess
      both an active zone and a reserve population. It was observed that the TTM
      response depressed more quickly than that of the DLM. To further explore the
      possible contribution of the reserve population to release, using the shibire
      mutant, DLM synapses were experimentally constructed that possess only the active
      zone population, and their depression characteristics were compared with those of
      the same synapses possessing both populations. It was observed that responses
      from DLM synapses possessing only the active zone population depressed more
      quickly than the same synapses possessing both populations. These experiments
      were conducted under conditions of blocked recycling so that the difference in
      stimulation tolerance represents the contribution of the reserve population to
      release. Furthermore, the depression curve of the DLM synapses lacking a reserve
      population now closely approximated that of the TTM synapses. These data suggest
      that the reserve vesicle population of DLM synapses may contribute to transmitter
      release during repetitive firing at physiological frequencies (5-10 Hz).

PMID- 15958602
TI  - Influence of path integration versus environmental orientation on place cell
      remapping between visually identical environments.
AB  - To assess the effects of interactions between angular path integration and visual
      landmarks on the firing of hippocampal neurons, we recorded from CA1 pyramidal
      cells as rats foraged in two identical boxes with polarizing internal cues. In
      the same-orientation condition, following an earlier experiment by Skaggs and
      McNaughton, the boxes were oriented identically and connected by a corridor. In
      the opposite-orientation condition, the boxes were abutted by rotating them 90
      degrees in opposite directions, so that their orientations differed by 180
      degrees . After 16-23 days of pretraining on the same-orientation condition,
      three rats experienced both conditions in counterbalanced order on each of two
      consecutive days. On the third day they ran two opposite-orientation trials.
      Although Skaggs and McNaughton observed stable partial "remapping" of place
      fields, none of the fields in this experiment remapped in the same-orientation
      condition. In the opposite-orientation condition, place fields in the first box
      were isomorphic with those in the same-orientation condition, whereas in the
      second box the rats eventually exhibited completely different fields. The rats
      differed as to the trial in which this first occurred. Once the second box
      exhibited different fields, it continued to do so in all subsequent opposite
      orientation trials, yet fields remained the same in subsequent same-orientation
      trials. The results demonstrate that when animals move actively between
      environments, and are thus potentially able to maintain their inertial angular
      orientation, discordance between environmental orientation and the rat's
      idiothetic direction sense can profoundly affect the hippocampal map-either
      immediately, or as a result of cumulative experience.

PMID- 15958603
TI  - Interlimb coordination during locomotion: what can be adapted and stored?
AB  - Interlimb coordination is critically important during bipedal locomotion and
      often must be adapted to account for varying environmental circumstances. Here we
      studied adaptation of human interlimb coordination using a split-belt treadmill,
      where the legs can be made to move at different speeds. Human adults, infants,
      and spinal cats can alter walking patterns on a split-belt treadmill by
      prolonging stance and shortening swing on the slower limb and vice versa on the
      faster limb. It is not known whether other locomotor parameters change or if
      there is a capacity for storage of a new motor pattern after training. We asked
      whether adults adapt both intra- and interlimb gait parameters during split-belt
      walking and show aftereffects from training. Healthy subjects were tested walking
      with belts tied (baseline), then belts split (adaptation), and again tied
      (postadaptation). Walking parameters that directly relate to the interlimb
      relationship changed slowly during adaptation and showed robust aftereffects
      during postadaptation. These changes paralleled subjective impressions of limping
      versus no limping. In contrast, parameters calculated from an individual leg
      changed rapidly to accommodate split-belts and showed no aftereffects. These
      results suggest some independence of neural control of intra- versus interlimb
      parameters during walking. They also show that the adult nervous system can adapt
      and store new interlimb patterns after short bouts of training. The differences
      in intra- versus interlimb control may be related to the varying complexity of
      the parameters, task demands, and/or the level of neural control necessary for
      their adaptation.

PMID- 15958604
TI  - Direct excitation of hypocretin/orexin cells by extracellular ATP at P2X
      receptors.
AB  - Hypocretin/orexin (hcrt) neurons play an important role in hypothalamic arousal
      and energy homeostasis. ATP may be released by neurons or glia or by pathological
      conditions. Here we studied the effect of extracellular ATP on hypocretin cells
      using whole cell patch-clamp recording in hypothalamic slices of transgenic mice
      expressing green fluorescent protein (GFP) exclusively in hcrt-producing cells.
      Local application of ATP induced a dose-dependent increase in spike frequency. In
      the presence of TTX, ATP (100 microM) depolarized the cells by 7.8 +/- 1.2 mV. In
      voltage clamp under blockade of synaptic activity with the GABA(A) receptor
      antagonist bicuculline, and ionotropic glutamate receptor antagonists DL-2-amino
      5-phosphonopentanoic acid (AP-5) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX),
      ATP (100 microM) evoked an 18 pA inward current. The inward current was blocked
      by extracellular choline substitution for Na+, had a reversal potential of -27
      mV, and was not affected by nominally Ca2+-free external buffer, suggesting that
      ATP activated a nonselective cation current. All excitatory effects of ATP showed
      rapid attenuation. ATP-induced excitatory actions were mimicked by
      nonhydrolyzable ATP-gamma-S but not by alpha,beta-MeATP and inhibited by the
      purinoceptor antagonists suramin and pyridoxal phosphate-6-azo(benzene-2,4
      disulfonic acid) tetrasodium salt (PPADS). The current was potentiated by a
      decrease in bath pH, suggesting P2X2 subunit involvement. Frequency and amplitude
      of spontaneous and miniature synaptic events were not altered by ATP. Suramin,
      but not PPADS, caused a small suppression of evoked excitatory synaptic
      potentials. Together, these results show a depolarizing response to extracellular
      ATP that would lead to an increased activity of the hypocretin arousal system.

PMID- 15958605
TI  - A novel model for prediction of human drug clearance by allometric scaling.
AB  - Sixty-one sets of clearance (CL) values in animal species were allometrically
      scaled for predicting human clearance. Unbound fractions (f(u)) of drug in plasma
      in rats and humans were obtained from the literature. A model was developed to
      predict human CL: CL=33.35 ml/min x (a/Rf(u))(0.770), where Rf(u) is the f(u)
      ratio between rats and humans and a is the coefficient obtained from allometric
      scaling. The new model was compared with simple allometric scaling and the "rule
      of exponents" (ROE). Results indicated that the new model provided better
      predictability for human values of CL than did ROE. It is especially significant
      that for the first time the proposed model improves the prediction of CL for
      drugs illustrating large vertical allometry.

PMID- 15958606
TI  - Translating research into clinical practice: deliberations from the American
      Association for Cancer Research.
AB  - Translational research is difficult to define but recognizable to all who engage
      in it. Academic medical centers struggle to participate effectively, in contrast
      to the biotechnology or pharmaceutical industry, which are designed for nothing
      else. The process of translational research can be viewed as a cycle with defined
      phases and identifiable checkpoints. From the original hypothesis, through early
      scientific testing, investigators with different skill sets are required to move
      a fundamental observation through preclinical tests of clinical relevance then
      ultimately into the clinic. The various investigators must be able to organize
      effective research teams, whose compositions will differ as one moves closer to
      treating patients. Each phase, from discovery through application, has a set of
      barriers that can be summarized as culture, human resources/education,
      infrastructure, and regulatory. At a retreat of the Clinical Translational
      Research Committee of the American Association for Cancer Research, many of the
      issues facing academic centers were discussed and several recommendations are
      summarized here.

PMID- 15958607
TI  - Getting at MYC through RAS.

PMID- 15958608
TI  - Regulation of fibroblast growth factor-2 activity by human ovarian cancer tumor
      endothelium.
AB  - Fibroblast growth factor-2 (FGF-2) is a potent angiogenic cytokine that is
      dependent on heparan sulfate for its biological activity. We have investigated
      the relationship among heparan sulfate, FGF-2, and the signal-transducing
      receptors in human, advanced-stage, serous ovarian adenocarcinoma. Using a unique
      molecular probe, FR1c-Ap, which consisted of a soluble FGF receptor 1 isoform
      IIIc covalently linked to an alkaline phosphatase moiety, the distribution of
      heparan sulfate that had the ability to support the formation of a heparan
      sulfate/FGF-2/FGFR1 isoform IIIc alkaline phosphatase heparan sulfate construct
      complex was determined. This may be taken as a surrogate marker for the
      distribution of biologically active heparan sulfate and was distributed
      predominantly in endothelial cells and stroma but was absent from adenocarcinoma
      cells. In situ hybridization revealed the expression of FGFR1 mRNA in the
      endothelium and reverse transcription-PCR confirmed the presence of FGFR1 isoform
      IIIc but not isoform IIIb. The presence of FGF-2 around tumor endothelium was
      detected through immunohistochemistry. Double-staining techniques showed that
      heparan sulfate was found predominantly at the basal aspect of the endothelium
      and suggested that syndecan-3 might function as one of the proteoglycans involved
      in FGF-2 signaling in the endothelium. The data suggest that the entire
      extracellular signaling apparatus, consisting of FGF-2, biologically active
      heparan sulfate, and FGFRs capable of responding to FGF-2, is present in ovarian
      cancer endothelium, thereby highlighting the cytokine and its cognate receptor as
      potential targets for the antiangiogenic treatment of this disease.

PMID- 15958609
TI  - Gefitinib-sensitive mutations of the epidermal growth factor receptor tyrosine
      kinase domain in chinese patients with non-small cell lung cancer.
AB  - PURPOSE: Studies have shown that mutations in the epidermal growth factor
      receptor (EGFR) tyrosine kinase domain are associated with response of lung
      cancer to gefitinib (Iressa, AstraZeneca Corp., Shanghai, China). A higher
      incidence of EGFR mutation was observed in non-small cell lung cancer (NSCLC)
      patients of Japanese origin compared with those of American origin. However, no
      data about such mutations in Chinese patients with NSCLC could be obtained.
      METHODS: Primary NSCLC tissues were obtained for analysis of mutations in exons
      18 to 21 of EGFR from a total of 76 patients, of whom 54 did not receive
      gefitinib therapy and 22 did. PCR products were sequenced directly and mutations
      were confirmed by an independent PCR and sequence analysis. All types of mutation
      were cloned and sequenced. RESULTS: A total of 10 types of mutation were found in
      the series of patients, including two different silent mutations in exon 20 from
      11 patients. More than half of the silent mutations (6 of 11) in exon 20
      coexisted with other mutations. Mutations were more frequent in adenocarcinoma
      (17 of 35; 48.6%) compared with squamous carcinoma (1 of 19; 5.3%) among
      untreated patients. Similar mutations were observed in all seven gefitinib
      treated patients with partial response, and no mutations were detected in all
      eight patients with progressive disease (P < 0.001), except two silent mutations.
      Three mutations were observed in seven patients with stable disease. CONCLUSIONS:
      Mutations in the epidermal growth factor receptor tyrosine kinase domain in lung
      adenocarcinomas from Chinese patients were more frequent than reported previously
      in lung adenocarcinomas from American patients. Such mutations were well
      correlated with tumor response to gefitinib.

PMID- 15958610
TI  - Elevated expression of Wnt antagonists is a common event in hepatoblastomas.
AB  - Hepatoblastomas are the most frequent malignant liver tumors of childhood. A high
      frequency of activating beta-catenin mutations in hepatoblastomas indicates that
      the Wnt signaling pathway plays an important role in the development of this
      embryonic neoplasm. Stabilization of beta-catenin leads to an increased formation
      of nuclear beta-catenin-T-cell factor complexes and altered expression of Wnt
      inducible target genes. In this study, we analyzed the mRNA expression levels of
      nine Wnt genes, including c-JUN, c-MYC, CYCLIN D1, FRA-1, NKD-1, ITF-2, MMP-7,
      uPAR, and beta-TRCP, by competitive reverse transcription-PCR. We analyzed 23
      hepatoblastoma biopsies for which matching liver tissue was available, 6
      hepatoblastoma cell lines, and 3 human fetal liver samples. beta-TRCP and NKD-1
      were highly expressed in all hepatoblastoma samples, independent of the beta
      catenin mutational status, in comparison with their nontumorous counterparts.
      beta-TRCP mRNA overexpression was associated with accumulation of
      intracytoplasmic and nuclear beta-TrCP protein. In human liver tumor cells
      without beta-catenin mutations, Nkd-1 inhibited the Wnt-3a-activated Tcf
      responsive-luciferase reporter activity, whereas Nkd-1 in hepatoblastomas with
      beta-catenin mutations had no antagonistic effect. Our data emphasize the
      inhibitory effect of beta-TrCP and Nkd-1 on the Wnt signaling pathway in a manner
      analogous to Conductin (AXIN2) and Dkk-1, inhibitors shown previously to be up
      regulated in hepatoblastomas. Our findings indicate that overexpression of the
      Wnt antagonists Nkd-1 and beta-TrCP reveals an activation of the Wnt signaling
      pathway as a common event in hepatoblastomas. We propose that Nkd-1 and beta-TrCP
      may be used as possible diagnostic markers for the activated Wnt signaling
      pathway in hepatoblastomas.

PMID- 15958611
TI  - Up-regulation of EphB4 in mesothelioma and its biological significance.
AB  - PURPOSE: Mesothelioma is a rare malignancy that is incurable and carries a short
      survival despite surgery, radiation, or chemotherapy. This study was designed to
      identify novel targets for diagnostic, prognostic, and therapeutic approaches.
      EXPERIMENTAL DESIGN: The expression and functional significance of the receptor
      tyrosine kinase EphB4 was studied in vitro and in a murine model of mesothelioma.
      RESULTS: EphB4 was highly expressed in mesothelioma cell lines and primary tumor
      tissues but not in normal mesothelium. Knockdown of EphB4 using small interfering
      RNA and antisense oligodeoxynucleotide showed reduction in cell survival,
      migration, and invasion. EphB4 knockdown initiated a caspase-8-mediated apoptosis
      and down-regulation of the anti-apoptotic protein bcl-xl. EphB4 knockdown also
      resulted in reduced phosphorylation of Akt and down-regulation of matrix
      metalloproteinase-2 transcription. In addition, murine tumor xenograft studies
      using EphB4 oligodeoxynucleotides showed a marked reduction in tumor growth
      accompanied by a specific decline in EphB4 protein levels, reduced cell division,
      apoptosis in tumor tissue, and decreased microvascular density. CONCLUSIONS:
      EphB4 is expressed in mesothelioma, provides a survival advantage to tumor cells,
      and is therefore a potential novel therapeutic target.

PMID- 15958612
TI  - Coxsackie and adenovirus receptor promotes adenocarcinoma cell survival and is
      expressionally activated after transition from preneoplastic precursor lesions to
      invasive adenocarcinomas.
AB  - PURPOSE: The cell adhesion protein, coxsackie and adenovirus receptor (CAR), is
      differentially expressed in various human adenocarcinomas. We analyzed the role
      of differential CAR expression during tumorigenesis and in cell survival of
      adenocarcinomas. EXPERIMENTAL DESIGN: In a murine mammary cancer model, a
      syngenic preneoplastic mammary tissue was implanted into the mammary fat pads of
      syngenic female BALB/c mice. CAR expression was determined by semiquantitative
      reverse transcription-PCR in the preneoplastic noninvasive precursor lesions and
      the developing invasive adenocarcinomas. Cell clones overexpressing CAR were
      generated and tested for their response to apoptotic factors and for the
      expression of apoptosis relevant proteins by reverse transcription-PCR and
      Western blot analysis. RESULTS: In comparison of preneoplastic precursor lesions
      with established adenocarcinomas, CAR expression was enhanced 2- to 5-fold in all
      six tissues which had survived and transformed into invasive adenocarcinomas.
      When stable CAR-overexpressing cell clones of the human cancer cell lines HeLa,
      CaSki, and A2780 were compared with the parental cell lines, 1.5- to 6-fold more
      cells survived application of tumor necrosis factor-related apoptosis-inducing
      ligand or growth factor withdrawal. CAR-enhanced cell survival was accompanied by
      reduced activation of caspase 3 and enhanced expression of bcl-2 or bcl-XL,
      depending on the cell type tested. Up-regulation of bcl-2 was found in all CAR
      expressing adenocarcinomas of the murine cancer model. CONCLUSIONS: CAR
      expression is enhanced after transition from preneoplastic precursor lesions to
      neoplastic mammary cancer outgrowths. Enhanced CAR expression can promote cancer
      cell survival. These data suggest differential expression of CAR as a new factor
      in tumorigenesis.

PMID- 15958613
TI  - Disruption of cooperation between Ras and MycN in human neuroblastoma cells
      promotes growth arrest.
AB  - PURPOSE: Our aim was to examine whether active Ras and MycN cooperation
      contributes to the malignant phenotype of human neuroblastoma with amplified MycN
      gene, an aggressive incurable tumor. EXPERIMENTAL DESIGN: Human neuroblastoma LAN
      1 cells, in which the MycN gene is amplified, were used to examine the impact of
      the Ras inhibitor farnesylthiosalicylic acid on cell growth, on the levels Ras
      and MycN proteins, and on profiles of gene expression. RESULTS: We show that LAN
      1 cells express relatively large amounts of MycN and active Ras-GTP. Inhibition
      of active Ras by farnesylthiosalicylic acid led to attenuation of the Raf-MEK-ERK
      and phosphoinositide 3-kinase-Akt-glycogen synthase-3 (GSK-3) pathways, to
      reduction in cyclin D1, phospho-retinoblastoma, and E2F, and to increase in the
      cyclin-dependent kinase inhibitor p27 and in retinoblastoma-binding protein-1, an
      inhibitor of E2F transcriptional activity. Ras inhibition by
      farnesylthiosalicylic acid or by a dominant-negative Ras also led to complete
      disappearance of MycN protein from the nuclei of LAN-1 cells. This was a result
      of blocking of Akt inactivation of GSK-3, leading to GSK-3-dependent
      phosphorylation with consequent proteosomal degradation of MycN. Loss of active
      Ras and of MycN in LAN-1 cells was manifested in profiles of gene expression that
      could be expected from the loss of MycN transcriptional activity and of Ras
      signaling. These changes explain the farnesylthiosalicylic acid-induced
      inhibition of LAN-1 cell growth. CONCLUSIONS: Active Ras is needed to block MycN
      degradation, promoting cooperative Ras- and MycN-dependent cell cycle progression
      in LAN-1 cells. Ras inhibitors are therefore likely candidates for the treatment
      of advanced neuroblastoma characterized by high expression of MycN.

PMID- 15958614
TI  - Differential expression of full-length telomerase reverse transcriptase mRNA and
      telomerase activity between normal and malignant renal tissues.
AB  - Activation of telomerase, a key event during immortalization and malignant
      transformation, requires expression of the telomerase reverse transcriptase
      (hTERT). Consistently, lack of telomerase activity and hTERT expression occurs in
      most normal human somatic cells. However, it has been observed that both normal
      and cancerous renal tissues express hTERT whereas only the latter exhibits
      telomerase activity. The mechanism underlying the dissociation between hTERT
      expression and telomerase activity is unclear. In the present study, we examined
      telomerase activity and alternative splicing of hTERT transcripts in renal cell
      carcinoma (RCC) specimens and adjacent normal tissues from 33 patients with RCC.
      Telomerase activity was detectable in 27 of 33 (82%) RCC samples but none in
      their normal counterparts. Thirty-two of 33 tumors expressed overall hTERT mRNA
      and 27 of them contained full-length hTERT transcripts, all with telomerase
      activity. Although 42% (14 of 33) of normal renal samples expressed hTERT mRNA,
      none of them had full-length hTERT transcripts, coinciding with lack of
      telomerase activity. The presence of full-length hTERT mRNA and telomerase
      activity was significantly associated with c-MYC induction. In tumors, absence of
      full-length hTERT mRNA or telomerase activity defines a subgroup of
      nonmetastatic, early-stage RCCs. Taken together, telomerase repression in normal
      renal tissues is attributed to the absence of full-length hTERT transcripts,
      whereas telomerase activation is achieved via induction of or switch to
      expression of full-length hTERT mRNA during the oncogenic process of kidneys, and
      associated with aggressive RCCs.

PMID- 15958615
TI  - Stability of phosphoprotein as a biological marker of tumor signaling.
AB  - PURPOSE: The purpose of the study was to evaluate the stability of phosphoprotein
      as a marker of signaling activity in human tumors using clinical samples and
      xenografts. EXPERIMENTAL DESIGN: The expression of phospho-Ser473-Akt (p-Akt) was
      assessed by immunohistochemistry in paraffin-embedded samples from patients
      enrolled in a Southwest Oncology Group clinical trial of gastroesophageal
      junction tumors and by immunohistochemistry and Western blotting in human colon
      tumor xenografts at various times after removal from the animal. RESULTS:
      Clinical samples had evaluable p-Akt staining only when obtained as biopsies (9
      of 13) and no staining was observed in tumors obtained as surgically resected
      samples (0 of 15). In HT-29 colon cancer xenografts, p-Akt staining was present
      in fresh sample but not in tissue that had been allowed to stand for 30 minutes
      at room temperature. Western blotting of HT-29 tumor xenografts at room
      temperature showed a slow decrease in total Akt with a half-life of 180 minutes
      and a rapid decrease in p-Akt with a half-life of 20 minutes. CONCLUSIONS:
      Caution should be used when using phosphoprotein levels in human tumor specimens
      to measure intrinsic signaling activity or drug effects because of the potential
      for rapid dephosphorylation. Rapid processing of biopsies is essential and
      postoperative surgical samples may be of limited value because of the time to
      fixation.

PMID- 15958616
TI  - 2-[11C]thymidine positron emission tomography reproducibility in humans.
AB  - PURPOSE: To evaluate the reproducibility of 2-[11C]thymidine positron emission
      tomography (PET) scanning in patients with advanced intra-abdominal malignancies.
      PATIENTS AND METHODS: The reproducibility of 2-[11C]thymidine PET was studied by
      comparing interpatient and intrapatient variability (coefficient of variability,
      COV) of both blood and tissue data. Arterial plasma metabolite levels were
      measured using on-line sampling and high-pressure liquid chromatography. 2
      [11C]Thymidine retention in tissue was measured as the standardized uptake value
      at the end of the scan (SUV(end)), the area under the time-activity curve (AUC(0
      1 hour)), and the fractional retention of thymidine (FRT). A group of seven
      patients were scanned 1 week apart with no intervening anticancer therapy.
      RESULTS: There was interpatient variability in the levels of 2-[11C]thymidine and
      its main metabolite, 11CO2, in plasma. Variability in 2-[11C]thymidine PET data
      was greater between (COV: SUV(end) = 38%, AUC(0-1 hour) = 32%, FRT = 47%) than
      within (COV: SUV(end) = 8%, AUC(0-1 hour) = 2%, FRT = 9%) patients. There was a
      borderline significant difference between the paired tumor data for SUV(end) (P =
      0.041), but not for AUC(0-1 hour) (P = 0.81) or FRT (P = 0.90). There was a good
      correlation between paired data for SUV(end) (r = 0.98), AUC(0-1 hour) (r =
      0.99), and FRT (r = 0.95). CONCLUSIONS: This is the first report showing that 2
      [11C]thymidine PET scanning is reproducible in humans. Repeat scanning of tumor
      proliferation using 2-[11C]thymidine PET is feasible to perform in human intra
      abdominal malignancies and should aid the future rapid assessment of
      antiproliferative tumor agents.

PMID- 15958617
TI  - Evaluation of the combined effect of p53 codon 72 polymorphism and hotspot
      mutations in response to anticancer drugs.
AB  - Mutations in p53 are common events during carcinogenesis and have been suggested
      to affect sensitivity to chemotherapy. Recently, the common polymorphism at codon
      72, resulting in either an arginine (72R) or proline (72P) residue, was shown to
      differentially affect the response to anticancer drugs. Here, we have generated
      isogenic lung cancer cell lines to evaluate the effect of six p53 hotspot
      mutations (R175H, G245S, R248W, R249S, R273H, and R282W) in conjunction with the
      codon 72 polymorphism, for their response to a variety of anticancer drugs,
      either alone or in combination. The data indicate that 72R mutations do not
      confer general resistance to cisplatin, etoposide, gemcitabine, vinblastine, and
      taxol. For doxorubicin, cells expressing 249-72R were more resistant than the 249
      72P cells. Combined treatment with cisplatin + etoposide resulted in an additive
      effect in cells expressing most 72R and 72P mutations, except for the 175-72R
      cells which were refractory to combined treatment. However, combined treatment
      with cisplatin + gemcitabine resulted in the absence of an additive effect in
      cells expressing the 273-72R and 282-72R mutants, unlike their 72P counterparts.
      Nonetheless, all p53 mutants (72R or 72P) equally inhibited p73-mediated
      transcriptional activity in lung cancer cells, suggesting that the selective
      resistance conferred by some 72R mutants to certain drugs is probably due to
      other p73-independent effects of these mutants. Together, the data show that the
      status of codon 72 polymorphism and p53 mutations can be used as a means for
      prediction of treatment response, although variables for each cancer type
      requires detailed evaluation.

PMID- 15958618
TI  - Aberrant expression of novel and previously described cell membrane markers in
      human breast cancer cell lines and tumors.
AB  - PURPOSE: In a previous gene expression array study, we identified some 300 genes
      that were differentially expressed in human epidermal growth factor receptor
      tyrosine kinase 2 (HER2)-positive versus HER2-negative breast cancer cells. We
      have now done validation experiments on a group of three cell membrane components
      that had previously not been implicated in breast cancer. We also studied the
      expression of three other cell membrane proteins known to play a role in mammary
      neoplasia. EXPERIMENTAL DESIGN: By immunohistochemistry, we examined up to 130
      archival breast carcinomas for Celsr2, E-cadherin, Kai1, and CD9 expression. The
      expression levels of NET-6 and TROP-2 were determined by quantitative reverse
      transcription-PCR in a subset of frozen tumors. We also studied fresh pellets and
      paraffin-embedded cell buttons of nine human breast cell lines. The relationship
      between the expression of all six membrane proteins and a variety of pathologic
      and biological variables, including estrogen receptor, HER2, and epidermal growth
      factor receptor status, was also examined. The NET-6 gene was transfected into a
      low-expressing cell line, and the effect on cellular morphology, growth, and
      invasion in vitro was recorded. RESULTS: Celsr2 was down-regulated in one cell
      line and in 7% of breast cancers. E-cadherin, Kai1, and CD9 were down-regulated
      in 35%, 76%, and 79% of tumors, respectively, confirming the important role of
      these markers in human mammary neoplasia. In breast cancer cell lines and
      tissues, TROP-2 was generally expressed at low levels, although a few specimens
      showed relative overexpression. NET-6 levels were lower in HER2-negative breast
      carcinoma cells. In addition, NET-6 was markedly down-regulated in estrogen
      receptor-negative breast cancers, and expression was lowest in "basal-like"
      tumors. Ectopic expression of NET-6 in low-expressing MDA-MB-231 cells altered
      cellular morphology, inhibited growth in vitro, and decreased invasion in a
      Boyden chamber assay. CONCLUSIONS: We have confirmed the expression of three new
      membrane markers that had previously not been implicated in human breast cancer,
      and one of them (NET-6) was correlated with HER2 and estrogen receptor status.
      NET-6 levels were decreased in estrogen receptor-negative and high-grade tumors,
      and ectopic expression of this gene had an inhibitory effect on proliferation and
      invasion. Thus, NET-6 may represent a novel breast cancer suppressor gene.

PMID- 15958619
TI  - Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer.
AB  - PURPOSE: Prostate cancer recurs during androgen deprivation therapy despite
      reduced circulating androgens. We showed that recurrent prostate cancer tissue
      has testosterone levels similar to androgen-stimulated benign prostate, whereas
      dihydrotestosterone levels were reduced 82% to 1.45 nmol/L, sufficient for
      androgen receptor activation. The altered testosterone/dihydrotestosterone ratio
      in recurrent prostate cancer suggests loss of 5alpha-reducing capability. The aim
      of this study was to characterize steroid 5alpha-reductase isozymes I (S5alphaRI)
      and II (S5alphaRII) in prostate tissues. EXPERIMENTAL DESIGN: A tissue microarray
      was constructed from 22 recurrent prostate cancer specimens and matched pairs of
      androgen-stimulated benign prostate and androgen-stimulated prostate cancer from
      23 radical prostatectomy specimens. Immunoblots were constructed from eight
      recurrent prostate cancers, eight androgen-stimulated benign prostate, and eight
      androgen-stimulated prostate cancer specimens. Isozyme expression was examined in
      microarray sections and immunoblots using S5alphaRI and S5alphaRII polyclonal
      antibodies. Isozyme activities were measured in 12 recurrent prostate cancer, 12
      androgen-stimulated benign prostate, and 12 androgen-stimulated prostate cancer
      specimens. RESULTS: Nuclear immunostaining exhibited higher S5alphaRI expression
      than S5alphaRII in recurrent prostate cancer, androgen-stimulated benign
      prostate, and androgen-stimulated prostate cancers (P < 0.0001); mean expression
      was 125, 150, and 115 for S5alphaRI versus 10, 29, and 37 for S5alphaRII,
      respectively. Cytoplasmic immunostaining was moderate and similar for both
      isozymes in the three tissue types (P > 0.05). Immunoblots confirmed
      immunohistochemistry; S5alphaRI was expressed in recurrent prostate cancer
      specimens and S5alphaRII was not detected. The activity of S5alphaRI (114.4
      pmol/mg epithelial protein/minute) was 3.7-fold higher than S5alphaRII (30.7
      pmol/mg epithelial protein/minute) in recurrent prostate cancer specimens.
      CONCLUSIONS: Expression levels and isozyme activity shifts from S5alphaRII toward
      S5alphaRI in recurrent prostate cancer. Dual inhibition of S5alphaRI and
      S5alphaRII should reduce dihydrotestosterone biosynthesis and may prevent or
      delay growth of recurrent prostate cancer.

PMID- 15958620
TI  - Down-regulated xanthine oxidoreductase is a feature of aggressive breast cancer.
AB  - PURPOSE: Xanthine oxidoreductase (XOR) is a key enzyme in the degradation of DNA,
      RNA, and high-energy phosphates and also plays a role in milk lipid globule
      secretion. Given the strong and regulated expression of XOR in normal breast
      epithelium, and the previously shown alterations of its expression in
      experimental tumorigenesis, we hypothesized that XOR may be differentially
      expressed in breast cancer. EXPERIMENTAL DESIGN: XOR expression was analyzed by
      immunohistochemistry in tissue microarray specimens of 1,262 breast cancer
      patients with a median follow-up of 9.5 years. RESULTS: Expression of XOR was
      moderately decreased in 50% and undetectable in another 7% of the tumors.
      Decreased XOR expression was associated with poor histologic grade of
      differentiation, ductal and lobular histologic types, large tumor size, high
      number of positive axillary lymph nodes, and high cyclooxygenase-2 expression,
      but not with estrogen or progesterone receptor status, Ki-67, p53, or ERBB2
      amplification. Absence of XOR expression was associated with unfavorable outcome,
      and patients with no XOR expression had more than twice the risk of distant
      recurrence as compared with those with a moderately decreased or normal
      expression (hazard ratio, 2.21; P < 0.0001). This was also true in patients with
      node-negative disease (hazard ratio, 2.75; P < 0.0001) as well as in patients
      with small (< or = 1 cm) tumors (hazard ratio, 3.09; P = 0.027). In a
      multivariate survival analysis, negative XOR emerged as an independent prognostic
      factor both in the entire series (P = 0.01) and among patients with node-negative
      disease (P = 0.0009). CONCLUSION: Loss of XOR identifies breast cancer patients
      with unfavorable prognosis.

PMID- 15958621
TI  - Effects of chemotherapy on the cytogenetic constitution of Wilms' tumor.
AB  - The management of Wilms' tumors consists of a combination of surgery,
      chemotherapy, and possibly radiotherapy. To date, chemotherapy is being risk
      stratified according to histologic subtype and stage. Although the cytogenetic
      characteristics of Wilms' tumors are well established, the cytogenetic effects
      related to chemotherapy are widely unknown. We herein report on comparative
      genomic hybridization findings in 41 primary Wilms' tumors of blastemal type, of
      which 19 had received preoperative chemotherapy (PCT group) and 22 did not (non
      PCT group). Overall, imbalances could be detected in 32 tumors, with +1q (17
      cases), +7q (10 cases), +7p (6 cases), and -7p (6 cases) as the most common
      changes. Among these, +7q and -7p were both significantly associated with
      metastatic disease at the time of surgery (P = 0.002 and 0.007, respectively),
      and +7q was also associated with higher stage (stages III + IV; P = 0.003). There
      were significant differences in the cytogenetic constitution of tumors between
      the two treatment groups. As a trend, tumors in the preoperative-chemotherapy
      group had fewer changes (mean, 2.7) than those in the non-preoperative
      chemotherapy group (mean, 3.8), and the frequencies of imbalances at 7p or +7q,
      respectively, were significantly lower compared with tumors in the non
      preoperative-chemotherapy group (2 of 19 versus 10 of 22, P = 0.019; 1 of 19
      versus 9 of 22, P = 0.011). In contrast, -1q was common in both the preop-CT
      group (10 of 19) and the non-preop-CT group (7 of 22). The results suggest that
      Wilms' tumor clones with +1q are not obliterated by preoperative chemotherapy,
      whereas cytogenetically more complex clones with +7q and/or imbalances at 7p seem
      more responsive and are more likely to be eliminated by chemotherapeutic
      treatment.

PMID- 15958622
TI  - Low-molecular weight caldesmon as a potential serum marker for glioma.
AB  - PURPOSE: Testing the feasibility of using the serum low-molecular weight
      caldesmon (l-CaD) level as a serum marker for the presence of glioma.
      EXPERIMENTAL DESIGN: Within a total of 230 serum samples, the l-CaD level was
      measured in healthy volunteers (30), patients with gliomas (57), nonglial
      intracranial tumors (107), and nontumor neurologic diseases (36) by ELISA. The
      specificity of the assay was monitored by combination of immunoprecipitation and
      immunoblotting. RESULTS: The serum level of l-CaD is significantly higher in the
      group of glioma patients as compared with any of the other groups (P < 0.001).
      The cutoff value of 45 yields optimal sensitivity and specificity of the assay
      (91% and 84%, respectively; area under the curve score = 0.91). The specificity
      of ELISA was confirmed by the immunoprecipitation/immunoblotting control
      experiments. There were no significant differences in serum l-CaD levels between
      patients with low- or high-grade gliomas. CONCLUSIONS: The serum l-CaD level as
      determined by ELISA is a good discriminator between glioma patients versus
      patients with other intracranial tumors, other neurologic diseases, and healthy
      people. Prospective studies are required to test the contribution of the assay in
      making the diagnosis of glioma, or its feasibility for monitoring the tumor
      during treatment.

PMID- 15958623
TI  - Polysomy 17 in HER-2/neu status elaboration in breast cancer: effect on daily
      practice.
AB  - PURPOSE: To assess the effect of chromosome 17 copy number on HER-2/neu status
      determination in breast cancers. EXPERIMENTAL DESIGN: HER-2/neu gene copy and
      chromosome 17 centromere numbers were evaluated on 893 breast carcinomas using
      double color fluorescence in situ hybridization (FISH). The net and chromosome 17
      corrected (ratio) HER-2/neu copy numbers were compared and related to
      immunohistochemistry done according to the Food and Drug Administration (FDA)
      approved scoring system (0, 1+, 2+, and 3+) as a first screening step in 584
      cases. RESULTS: When a ratio > or = 2 was considered as criterion for FISH
      positivity, 49.3% (440 of 893) of cases showed amplification versus 56.2% (502 of
      893) by using a net HER-2/neu gene copy number >4 as a alternative criterion;
      14.8% (67 of 453) of cases having a ratio <2 had a net HER-2/neu gene copy number
      >4 and 1.1% (5 of 440) with a ratio > or = 2 had a net HER-2/neu gene copy number
      <4. Among discordant cases, 88.8% (64 of 72) were polysomic (>2.25 chromosomes
      17/cell) and among polysomic cases, 12.8% (40 of 312) of the low polysomic (2.26
      3.75 chromosomes 17/cell) and 36.9% (24 of 65) of the highly polysomic (>3.75
      chromosomes 17/cell) cases showed discordance. In cases with a ratio <2, polysomy
      17 incidences were 85.7% (6 of 7) in IHC 3+, 42.4% (79 of 186) in IHC 2+, 33.3%
      (15 of 45) in IHC 1+, and 29.1% (16 of 55) in IHC 0. CONCLUSION: A net increase
      in HER-2/neu gene copy number consecutive to polysomy 17 in the absence of
      specific gene amplification might lead to a strong protein overexpression in a
      small subset of breast carcinomas. HER-2/neu status determination by FISH is
      dependent on the criterion considered for positivity in clinical practice.

PMID- 15958624
TI  - Methylation profiling of archived non-small cell lung cancer: a promising
      prognostic system.
AB  - PURPOSE: Enhanced prognostication power is becoming more desirable in clinical
      oncology. In this study, we explored the prognostic potential of multigene
      hypermethylation profiling in non-small-cell lung cancer. EXPERIMENTAL DESIGN: We
      evaluated a panel of eight genes (p16, APC, ATM, hMLH1, MGMT, DAPK, ECAD, and
      RASSF1A) using methylation-specific PCR in 105 archived specimens of non-small
      cell lung cancer representing all stages of the illness. We analyzed the effect
      of gene methylation status on outcome individually in a cumulative manner and in
      a combinatorial approach using recursive partitioning to identify methylation
      profiles, which affect overall survival. RESULTS: In this data set, tumors
      harboring promoter hypermethylation at two or more genes exhibit similar survival
      trends to others in the cohort. Using recursive partitioning, three genes (APC,
      ATM, and RASSF1A) emerged as determinants of prognostic groups. This designation
      retained its statistical significance even when disease stage and age were
      entered into a multivariate analysis. Using this approach, patients whose tumors
      were hypermethylated at APC and those hypermethylated at only ATM (not also at
      APC or RASSF1A) enjoyed substantially longer 1- and 2-year survival than patients
      in the remaining groups. In 32 adjacent histologically normal lung tissue
      specimens, we detected similar methylation abnormalities. CONCLUSION: Assessment
      of promoter hypermethylation aberrations may facilitate prognostic profiling of
      lung tumors, but validation in independent data sets is needed to verify these
      profiles. This system uses material that is abundantly available with linked
      outcome data and can be used to generate reliable epigenetic determinants.

PMID- 15958625
TI  - Validation of genomics-based prognostic tests in malignant pleural mesothelioma.
AB  - PURPOSE: Malignant pleural mesothelioma (MPM) is a highly lethal neoplasm with
      limited pretreatment prognostication strategies. In this report, we examine the
      accuracy of a previously proposed prognostic test in an independent cohort of MPM
      patients. This test uses simple ratios of gene expression levels to provide a
      novel prognostication scheme. EXPERIMENTAL DESIGN: Gene expression data using
      high-density oligonucleotide microarrays (approximately 22,000 genes) were
      obtained for a new cohort of human MPM tumors from patients undergoing similar
      treatments (n = 39). The relative expression levels for specific genes were also
      determined using real-time quantitative reverse transcription-PCR. We also used a
      subset of these tumors associated with widely divergent patient survival (n = 23)
      as a training set to identify new treatment-specific candidate prognostic
      molecular markers and gene ratio-based prognostic tests. The predictive nature of
      these newly discovered markers and gene ratio-based prognostic tests were then
      examined in an independent group of tumors (n = 52) using microarray data and
      quantitative reverse transcription-PCR. RESULTS: Previously described MPM
      prognostic genes and gene ratio-based prognostic tests predicted clinical outcome
      in 39 independent MPM tumor specimens in a statistically significant manner.
      Newly discovered treatment-specific prognostic genes and gene ratio-based
      prognostic tests were highly accurate and statistically significant when examined
      in an independent group of 52 tumors from patients undergoing similar treatment.
      CONCLUSIONS: The data support the use of gene ratios in translating gene
      expression data into easily reproducible, statistically validated clinical tests
      for the prediction of outcome in MPM.

PMID- 15958626
TI  - Gene expression profiling of progressive papillary noninvasive carcinomas of the
      urinary bladder.
AB  - PURPOSE: The aim of the present study was to define gene expression profiles of
      noninvasive and invasive bladder cancer, to identify potential therapeutic or
      screening targets in bladder cancer, and to define genetic changes relevant for
      tumor progression of recurrent papillary bladder cancer (pTa). EXPERIMENTAL
      DESIGN: Overall, 67 bladder neoplasms (46 pTa, 3 pTis, 10 pT1, and 8 pT2) and
      eight normal bladder specimens were investigated by a combination of laser
      microdissection and gene expression profiling. Eight of 16 patients with
      recurrent noninvasive papillary bladder tumors developed carcinoma in situ (pTis)
      or invasive bladder cancer (> or = pT1G2) in the course of time. RNA expression
      results of the putative progression marker cathepsin E (CTSE) were confirmed by
      immunohistochemistry using high-throughput tissue microarray analysis (n = 776).
      Univariate analysis of factors regarding overall survival, progression-free
      survival, and recurrence-free survival in patients with urothelial bladder cancer
      was done. RESULTS: Hierarchical cluster analyses revealed no differences between
      pTaG1 and pTaG2 tumors. However, distinct groups of invasive cancers with
      different gene expression profiles in papillary and solid tumors were found.
      Progression-associated gene profiles could be defined (e.g., FABP4 and CTSE) and
      were already present in the preceding noninvasive papillary tumors. CTSE
      expression (P = 0.003) and a high Ki-67 labeling index of at least 5% (P = 0.01)
      were the only factors that correlated significantly with progression-free
      survival of pTa tumors in our gene expression approach. CONCLUSIONS: Gene
      expression profiling revealed novel genes with potential clinical utility to
      select patients that are more likely to develop aggressive disease.

PMID- 15958627
TI  - Unexpected association between induction of immunity to the universal tumor
      antigen CYP1B1 and response to next therapy.
AB  - PURPOSE: The carcinogen activator cytochrome P450 1B1 (CYP1B1) is expressed on
      almost all human tumors with rare expression on normal tissues. Anti-CYP1B1
      specific T cells kill CYP1B1-expressing tumors, providing the rationale to
      examine CYP1B1 as a target for immunotherapy. EXPERIMENTAL DESIGN: ZYC300, a
      plasmid DNA of CYP1B1 encapsulated in biodegradable poly-DL-lactide-coglycolide
      microparticles, was used in a phase I clinical trial to treat 17 patients with
      advanced stage, progressive cancer. ZYC300 was administered i.m. at a fixed dose
      of 400 microg every other week for up to 12 doses. RESULTS: Thirteen patients
      received six vaccinations and five received all 12 doses. No significant adverse
      events were observed. Six patients developed immunity to CYP1B1, three of whom
      developed disease stabilization. All but 1 of 11 patients who did not develop
      immunity to CYP1B1 progressed and did not respond to salvage therapy. Five
      patients who developed immunity to CYP1B1 required salvage therapy for
      progressive metastatic disease and showed marked response to their next treatment
      regimen, most of which lasted longer than 1 year. CONCLUSIONS: The association
      between immunity to CYP1B1 and response to next salvage therapy was not expected.
      Because six of the seven patients who had clinical benefit regardless of the
      nature of salvage therapy had developed immunity to CYP1B1, it seems highly
      unlikely that this occurred by chance alone. Regardless of the mechanism(s) that
      induced tumor regression, these findings force us to rethink how the generation
      of antitumor immunity might be integrated into the treatment of cancer.

PMID- 15958628
TI  - Marimastat in the treatment of patients with biochemically relapsed prostate
      cancer: a prospective randomized, double-blind, phase I/II trial.
AB  - PURPOSE: To evaluate the safety and biological activity of three different doses
      of marimastat given for 6 months to patients with biochemically relapsed prostate
      cancer. EXPERIMENTAL DESIGN: Patients with a biochemical relapse within 2 years
      of primary therapy, a prostate-specific antigen (PSA) increase of at least 50%
      within 6 months of study entry, and no prior systemic therapy were eligible.
      Patients were randomized to receive marimastat at total daily doses of 5, 20, or
      40 mg for 6 months unless dose-limiting toxicity or new evidence of disease
      occurred. RESULTS: Thirty-nine patients were treated. Grade 3-4 reversible
      musculoskeletal toxicity was the only dose-limiting toxicity. Increasing dose was
      associated with increased probability of experiencing dose-limiting toxicity
      (5.9%, 42.9% and 88.9% for the 5, 20, and 40 mg groups, respectively; P = 0.03).
      Accrual was discontinued early on the two higher dose levels due to toxicity. A
      significant decrease in PSA slope was shown in the 20 mg group when compared with
      the 5 mg group (0.117 and -0.0046, respectively; P = 0.03) The 40 mg group
      (versus the 5 mg group) showed a similar change (0.109) with a trend towards
      significance (P = 0.07). An increased serum matrix metalloproteinase 2 level at
      month 3 compared with the baseline correlated with a decrease in PSA slopes
      (Slope, 0.001; 95% confidence interval, 0.0002-0.0018; P = 0.02). CONCLUSION:
      These data suggest that marimastat has a biological effect and may effectively
      delay progression in patients with biochemical relapsed prostate cancer, as shown
      by the change in PSA slope; however, dose-limiting toxicity at active doses is
      significant. Confirmatory studies with less toxic matrix metalloproteinase
      inhibitors employing more conventional end points are indicated. This design is
      feasible and potentially efficient for screening antimetastatic agents.

PMID- 15958629
TI  - The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid
      tumors: a California cancer consortium phase I pharmacokinetic and molecular
      correlative trial.
AB  - BACKGROUND: UCN-01 (7-hydroxy-staurosporine) is a novel antineoplastic agent
      targeting cyclin-dependent kinases, which shows potent in vitro and in vivo
      activity against a broad range of tumor types. Our group has previously shown
      that UCN-01 potentiates the apoptotic response of agents such as cisplatin in
      vitro by preventing sequence-specific abrogation of G2 arrest caused by DNA
      damaging chemotherapies. PATIENTS AND METHODS: This National Cancer Institute
      sponsored phase I trial was designed to determine the safety, maximum tolerated
      dose, and pharmacokinetics of escalating doses of cisplatin in combination with
      UCN-01 in patients with advanced malignant solid tumors, as well as to do
      molecular correlative studies on tumor specimens. Cisplatin was infused over 1
      hour before UCN-01 (45 mg/m2/d) given as a 72-hour continuous infusion.
      Escalation of cisplatin was planned through five dose levels at 20, 30, 45, 60,
      and 75 mg/m2. RESULTS: Ten patients were accrued. Accrual was halted at dose
      level 2 (cisplatin, 30 mg/m2) due to dose-limiting toxicities consisting of grade
      5 sepsis with respiratory failure associated with grade 3 creatinine (one
      patient) and grade 3 atrial fibrillation (one patient). Plasma and salivary
      pharmacokinetics of UCN-01 were unaffected by cisplatin. Pretreatment and
      posttreatment tumor biopsies showed that UCN-01 was active against a key
      molecular target, the checkpoint kinase Chk1. CONCLUSIONS: This phase I trial
      failed to achieve targeted therapeutic dose levels of cisplatin when combined
      with prolonged infusion UCN-01. However, because preclinical data indicate that
      UCN-01 potentiates response to platinum, further studies with alternative dose
      schedules of the combination, or with other platinum analogues, are warranted.

PMID- 15958630
TI  - First clinical experience with alpha-emitting radium-223 in the treatment of
      skeletal metastases.
AB  - PURPOSE: The main goals were to study the safety and tolerability of the alpha
      emitter radium-223 (223Ra) in breast and prostate cancer patients with skeletal
      metastases. In addition, pain palliation was evaluated. EXPERIMENTAL DESIGN:
      Fifteen prostate and 10 breast cancer patients enrolled in a phase I trial
      received a single i.v. injection of 223Ra. Five patients were included at each of
      the dosages: 46, 93, 163, 213, or 250 kBq/kg and followed for 8 weeks. Palliative
      response was evaluated according to the pain scale of the European Organization
      for Research and Treatment of Cancer QLQ C30 questionnaire at baseline and at 1,
      4, and 8 weeks after injection. RESULTS: Weekly blood sampling during follow-up
      revealed mild and reversible myelosuppression with nadir 2 to 4 weeks after the
      injection. Importantly, for thrombocytes only grade 1 toxicity was reported.
      Grade 3 neutropenia and leucopenia occurred in two and three patients,
      respectively. Mild, transient diarrhea was observed in 10 of the 25 patients.
      Nausea and vomiting was more frequently observed in the highest dosage group.
      Serum alkaline phosphatase decreased with nadir averages of 29.5% in females and
      52.1% in males. Pain relief was reported by 52%, 60%, and 56% of the patients
      after 7 days, 4, and 8 weeks, respectively. 223Ra cleared rapidly from blood and
      was below 1% of initial level at 24 hours. Gamma camera images indicated, in
      accordance with pretreatment (99m)Tc-MDP scans, accumulation of 223Ra in skeletal
      lesions. Elimination was mainly intestinal. Median survival exceeded 20 months.
      CONCLUSIONS: 223Ra was well tolerated at therapeutically relevant dosages. Phase
      II studies have therefore been initiated.

PMID- 15958631
TI  - Combination of imatinib mesylate with autologous leukocyte-derived heat shock
      protein and chronic myelogenous leukemia.
AB  - PURPOSE: To test the feasibility, safety, immunogenicity, and clinical efficacy
      of an autologous vaccine of leukocyte-derived heat shock protein 70-peptide
      complexes (Hsp70PC), in conjunction with imatinib mesylate, in patients with
      chronic myeloid leukemia (CML) in chronic phase. EXPERIMENTAL DESIGN: Patients
      had cytogenetic or molecular evidence of disease, despite treatment with imatinib
      mesylate for all except one patient, at the beginning of study. Hsp70PCs were
      purified from the leukopheresed peripheral blood mononuclear cells and were
      administered in eight weekly intradermal injections at 50 microg/dose without
      adjuvant. Clinical responses were assessed by bone marrow analysis before and
      after vaccinations. An IFN-gamma enzyme-linked immunospot assay was used to
      estimate the effect of treatment on natural killer cells and T cells against CML.
      RESULTS: Twenty patients were treated. The manufacturing of Hsp70PCs was
      successful and the administration was safe for all patients. Minimal or no side
      effects were reported. Clinical responses were seen in 13 of 20 patients as
      measured by cytogenetic analysis of bone marrow Philadelphia chromosome-positive
      cells in metaphases and/or, when possible, the level of Bcr/Abl transcript by
      PCR. Immunologic responses were observed in 9 of 16 patients analyzed,
      characterized by an increase in the frequency of CML-specific IFN-gamma-producing
      cells and IFN-gamma-secreting natural killer cells in the blood. A significant
      correlation between clinical responses and immunologic responses was observed.
      CONCLUSIONS: Autologous Hsp70PC vaccination is feasible and safe. When combined
      with imatinib mesylate, it is associated with immunologic and possible clinical
      responses against CML in chronic phase.

PMID- 15958632
TI  - Delayed disease progression after allogeneic cell vaccination in hormone
      resistant prostate cancer and correlation with immunologic variables.
AB  - PURPOSE: There are a significant number of patients with asymptomatic hormone
      resistant prostate cancer who have increasing prostate-specific antigen (PSA)
      levels but little or no evaluable disease. The immunogenicity and minimal
      toxicity associated with cell-based vaccine therapy makes this approach
      attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine
      comprising monthly intradermal injection of three irradiated allogeneic prostate
      cell lines (8 x 10(6) cells each) over 1 year. The first two doses were
      supplemented with bacille Calmette-Guerin as vaccine adjuvant. Twenty-eight
      hormone-resistant prostate cancer patients were enrolled. Patients were assessed
      clinically and PSA levels were measured monthly. Radiologic scans (X-ray,
      computed tomography, and bone scan) were taken at baseline and at intervals
      throughout the treatment period. Comprehensive monthly immunologic monitoring was
      undertaken including proliferation studies, activation markers, cytokine protein
      expression, and gene copy number. This longitudinal data was analyzed through
      predictive modeling using artificial neural network feed-forward/back-propagation
      algorithms with multilayer perceptron architecture. RESULTS: Eleven of the 26
      patients showed statistically significant, prolonged decreases in their PSA
      velocity (PSAV). None experienced any significant toxicity. Median time to
      disease progression was 58 weeks, compared with recent studies of other agents
      and historical control values of around 28 weeks. PSAV-responding patients showed
      a titratable T(H)1 cytokine release profile in response to restimulation with a
      vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response.
      Furthermore, immunologic profile correlated with PSAV response by artificial
      neural network analysis. We found predictive power not only in expression of
      cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but
      also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement
      tumor necrosis factor-alpha > protein expression of IFN-gamma > protein
      expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in
      hormone-resistant prostate cancer is nontoxic and improves the natural history of
      the disease. Longitudinal changes in immunologic function in vaccinated patients
      may be better interpreted through predictive modeling using tools such as the
      artificial neural network rather than periodic "snapshot" readouts.

PMID- 15958633
TI  - Targeting the c-Met pathway potentiates glioblastoma responses to gamma
      radiation.
AB  - PURPOSE: Resistance to current cytotoxic therapies limits the treatment of most
      solid malignancies. This results, in part, from the overactivation of receptor
      tyrosine kinases and their downstream pathways in tumor cells and their
      associated vasculature. In this report, we ask if targeting the multifunctional
      mitogenic, cytoprotective, and angiogenic scatter factor/hepatocyte growth factor
      (SF/HGF)/c-Met pathway potentiates antitumor responses to gamma-radiation.
      EXPERIMENTAL DESIGN: Endogenous expression of SF/HGF and c-Met was targeted in
      U87 MG human malignant glioma cells and xenografts using chimeric U1/ribozymes.
      The effects of U1/ribozymes +/- gamma-radiation on glioma cell proliferation,
      apoptosis, xenograft growth, and animal survival were examined. RESULTS:
      U1/ribozymes knocked down SF/HGF and c-Met mRNA and protein levels, sensitized
      cells to gamma-radiation (P < 0.005), and enhanced radiation-induced caspase
      dependent cytotoxicity in vitro (P < 0.005). Intravenous U1/ribozyme therapy as
      liposome/DNA complexes or radiation alone modestly and transiently inhibited the
      growth of s.c. U87 xenografts. Combining the therapies caused tumor regression
      and a 40% tumor cure rate. In animals bearing intracranial xenografts, long-term
      survival was 0% in response to radiation, 20% in response to intratumoral
      adenoviral-based U1/ribozyme delivery, and 80% (P < 0.0005) in response to
      combining U1/ribozymes with radiation. This apparent synergistic antitumor
      response was associated with a approximately 70% decrease in cell proliferation
      (P < 0.001) and a approximately 14- to 40-fold increase in apoptosis (P < 0.0001)
      within xenografts. CONCLUSIONS: Targeting the SF/HGF/c-Met pathway markedly
      potentiates the anti-glioma response to gamma-radiation. Clinical trials using
      novel SF/HGF/c-Met pathway inhibitors in glioma and other malignancies associated
      with c-Met activation should ultimate include concurrent radiation and
      potentially other cytotoxic therapeutics.

PMID- 15958634
TI  - In vivo RNA interference-mediated ablation of MDR1 P-glycoprotein.
AB  - Multidrug resistance (MDR) remains a major obstacle to successful
      chemotherapeutic treatment of cancer and can be caused by overexpression of P
      glycoprotein, the MDR1 gene product. To further validate a knockdown approach for
      circumventing MDR, we developed a P-glycoprotein inhibition strategy using short
      hairpin RNA interference (shRNAi) and now show efficacy and target specificity in
      vivo. Two of eight tested shRNAi constructs targeted against human MDR1 mRNA
      inhibited expression of P-glycoprotein by >90%, whereas control shRNAi had no
      effect. Ablation of P-glycoprotein in cells stably transduced with retroviral
      mediated shRNAi was documented by Western blot and functionally confirmed by
      increased sensitivity of MDR1-transfected cells toward the cytotoxic drugs
      vincristine, paclitaxel, and doxorubicin as well as by transport of (99m)Tc
      Sestamibi. shRNAi-mediated down-regulation of P-glycoprotein transport activity
      both in cultured cells and in tumor implants in living animals could be followed
      by direct noninvasive bioluminescence imaging using the Renilla luciferase
      fluorophore, coelenterazine, a known P-glycoprotein transport substrate.
      Furthermore, after somatic gene transfer by hydrodynamic infusion of a MDR1
      Firefly luciferase (MDR1-FLuc) fusion construct into mouse liver, the effect of
      shRNAi delivered in vivo on P-glycoprotein-FLuc protein levels was documented
      with bioluminescence imaging using d-luciferin. ShRNAi against MDR1 reduced
      bioluminescence output of the P-glycoprotein-FLuc reporter 4-fold in vivo
      compared with mice treated with control or scrambled shRNAi. Targeted down
      regulation of a somatically transferred P-glycoprotein-eGFP fusion reporter also
      was observed using fluorescence microscopy. Our results show that shRNAi
      effectively inhibited MDR1 expression and function in cultured cells, tumor
      implants and mammalian liver, documenting the feasibility of a knockdown approach
      to reversing MDR in vivo.

PMID- 15958635
TI  - In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40
      ligand-activated B cells gene modified to express primary granule proteins.
AB  - The primary granule proteins (PGP) of myeloid cells are a source of multiple
      antigens with immunotherapeutic potential for myeloid leukemias. Therefore, we
      developed a method to induce T-cell responses to PGP protein sequences. We found
      that gene-transfected antigen-presenting cells efficiently expand functionally
      competent PGP-specific CD4 and CD8 T cells. The system was optimized using T-cell
      responses to autologous CD40-activated B cells (CD40-B) transfected with a
      cytomegalovirus pp65-encoding expression vector. To generate leukemia-specific T
      cells, expression vectors encoding the PGP proteinase 3 (PR3), human neutrophil
      elastase, and cathepsin-G were transfected into CD40-B cells to stimulate post
      allogeneic stem cell transplantation T cells from five patients with myeloid and
      three with lymphoid leukemias. T-cell responses to PGP proteinase 3 and human
      neutrophil elastase were observed in CD8+ and CD4+ T cells only in patients with
      myeloid leukemias. T-cell responses against cathepsin-G occurred in both myeloid
      and lymphoblastic leukemias. T cells from a patient with chronic myelogenous
      leukemia (CML) and from a posttransplant CML patient, expanded against PGP,
      produced IFN-gamma or were cytotoxic to the patient's CML cells, demonstrating
      specific antileukemic efficacy. This study emphasizes the clinical potential of
      PGP for expansion and adoptive transfer of polyclonal leukemia antigen-specific T
      cells to treat leukemia.

PMID- 15958636
TI  - Graft-versus-leukemia target antigens in chronic myelogenous leukemia are
      expressed on myeloid progenitor cells.
AB  - PURPOSE: Donor lymphocyte infusion (DLI) reliably induces durable remission in
      75% to 80% of patients with relapsed chronic myelogenous leukemia (CML) following
      allogeneic bone marrow transplantation. We previously reported the identification
      of a high titer-specific immunoglobulin G response against two novel leukemia
      associated antigens, CML28 and CML66, which correlated with immune-induced
      remission. The present studies characterize expression of CML28 and CML66 in
      primary hematopoietic tissues. EXPERIMENTAL DESIGN: Specific monoclonal
      antibodies to CML28 and CML66 were developed and used to detect antigen
      expression in leukemia cell lines and primary leukemia tissue on Western blot and
      immunohistochemistry. Expression patterns were confirmed by antigen-specific real
      time PCR. RESULTS: Both CML28 and CML66 were highly expressed in leukemic blasts
      from patients with acute myelogenous leukemia and CML blast crisis but barely
      detectable in normal bone marrow, normal peripheral blood, or leukemic cells from
      patients with stable-phase CML. In contrast, purified CD34+ progenitors from
      normal individuals and patients with stable-phase CML expressed high levels of
      CML28 and CML66 transcript and protein. Immunohistochemical staining for CML66
      confirmed rare staining of myeloid precursors in normal marrow and diffuse
      staining of myeloblastic cells in acute myelogenous leukemia and blast crisis CML
      marrows. CONCLUSIONS: The expression patterns of CML28 and CML66 are strikingly
      similar and suggest that antigen expression may play a role in shaping the post
      DLI antibody repertoire. The CD34+ restricted pattern of expression of CML28 and
      CML66 is particularly relevant in light of the notion that DLI likely exerts its
      curative effect by targeting antigens present in self-renewing malignant
      progenitor populations in CML.

PMID- 15958637
TI  - Blockade of transforming growth factor-beta signaling suppresses progression of
      androgen-independent human prostate cancer in nude mice.
AB  - We investigated the role of transforming growth factor-beta (TGF-beta) signaling
      in the growth and metastasis of PC-3MM2 human prostate cancer cells. Highly
      metastatic PC-3MM2 human prostate cancer cells were engineered to constitutively
      overexpress a dominant-negative type II TGF-beta receptor (DNR). Transfection of
      DNR had minimal direct effects on cell growth and attenuated TGF-beta-induced
      cell growth inhibition and TGF-beta1 production. There were no discernable
      differences in tumorigenicity (tumor incidence) among PC-3MM2 variants when the
      cells were implanted into the prostates of nude mice. Growth rate and metastatic
      incidence of DNR-engineered PC-3MM2 cells, however, were significantly reduced.
      Most cells in the control tumors were positively stained by an antibody to
      proliferation cell nuclear antigen and very few cells were stained by terminal
      deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL). In sharp
      contrast, tumors formed by PC-3MM2-DNR cells contained fewer proliferation cell
      nuclear antigen-positive cells and many more TUNEL-positive cells. Staining with
      antibody against CD31 showed that control tumors contained more blood vessels
      than PC-3MM2-DNR tumors. Expression of interleukin-8 (IL-8) in tumors formed by
      PC-3MM2 cells was significantly reduced as revealed by both Northern blotting and
      ELISA. Finally, transfection of antisense IL-8 cDNA significantly reduced IL-8
      production by PC-3MM2 cells and antisense IL-8-transfected PC-3MM2 cells grew
      slower in comparison with parental and control vector-transfected cells. Taken
      together, our data suggest that TGF-beta signaling, by regulating IL-8 expression
      in tumor cells and hence tumor angiogenesis, is critical for progressive growth
      of PC-3MM2 cells in the prostate of nude mice.

PMID- 15958638
TI  - The antitumor and antiangiogenic activity of vascular endothelial growth factor
      receptor inhibition is potentiated by ErbB1 blockade.
AB  - PURPOSE: Receptor tyrosine kinases of the ErbB family play important roles in the
      control of tumor growth. Vascular endothelial growth factor (VEGF) stimulates
      endothelial cell proliferation, enhances vascular permeability, and plays an
      important role in tumor vascularization. We evaluated the effects of selective
      VEGF receptor (VEGFR; PTK787/ZK222584) and ErbB (PKI166 and ZD1839) inhibitors on
      tumor growth and angiogenesis and asked whether additional therapeutic benefit
      was conferred by combination treatment. EXPERIMENTAL DESIGN: The antitumor
      activity of each inhibitor alone or in combination was assessed in human cancer
      models in immunocompromised mice. ErbB receptor expression and activation of
      downstream signaling pathway was evaluated in both tumor and endothelial cells.
      RESULTS: Both ErbB inhibitors significantly enhanced the antitumor activity of
      PTK787/ZK222584. In vitro, ErbB1 inhibition blocked VEGF release by tumor cells
      and proliferation of both tumor and endothelial cells. In an in vitro
      angiogenesis assay, epidermal growth factor (EGF) stimulated the release of VEGF
      by smooth muscle cells resulting in increased angiogenesis, a response blocked by
      administration of PTK787/ZK222584. Under basal condition, both ZD1839 and
      PTK787/ZK222584 blocked sprouting, likely via inhibition of an autocrine ErbB1
      loop and VEGFR signaling, respectively, in endothelial cells. In conditions of
      limiting VEGF, EGF plays an important role in endothelial cell proliferation,
      survival, and sprouting. CONCLUSION: We have shown that activation of ErbB1
      triggers a plethora of effects, including direct effects on tumor and endothelial
      cells and indirect effects mediated via induction of VEGF release. Simultaneous
      blockade of ErbB1 and VEGFR pathways results in a cooperative antitumor effect,
      indicating that this combination may represent a valid therapeutic strategy.

PMID- 15958639
TI  - The requirement of multimodal therapy (vaccine, local tumor radiation, and
      reduction of suppressor cells) to eliminate established tumors.
AB  - PURPOSE: Numerous immune-based strategies are currently being evaluated for
      cancer therapy in preclinical models and clinical trials. Whereas many strategies
      look promising in preclinical models, they are often evaluated before or shortly
      following tumor implantation. The elimination of well-established tumors often
      proves elusive. Here we show that a multimodal immune-based therapy can be
      successfully employed to eliminate established tumors. EXPERIMENTAL DESIGN: This
      therapy consists of vaccines directed against a self-tumor-associated antigen,
      the use of external beam radiation of tumors to up-regulate Fas on tumor cells,
      and the use of a monoclonal antibody (mAb) to reduce levels of CD4+CD25+
      suppressor cells. RESULTS: We show here for the first time that (a) antigen
      specific immune responses induced by vaccines were optimally augmented when anti
      CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb
      administration in combination with vaccines equally augmented T-cell immune
      responses specific for a self-antigen as well as those specific for a non-self
      antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced
      antigen-specific immune responses, it was not sufficient to eliminate established
      tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti
      CD25 mAb regimen was required for the elimination of established tumors; and (e)
      T cells from mice receiving the combination therapy showed significantly higher T
      cell responses specific not only for the antigen in the vaccine but also for
      additional tumor-derived antigens (p53 and gp70). CONCLUSIONS: These studies
      reported here support the rationale for clinical trials employing multimodal
      immune-based therapies.

PMID- 15958640
TI  - Recognition of six-transmembrane epithelial antigen of the prostate-expressing
      tumor cells by peptide antigen-induced cytotoxic T lymphocytes.
AB  - The identification of novel markers and therapeutic targets in advanced cancer is
      critical for improving diagnosis and therapy. Six-transmembrane epithelial
      antigen of the prostate (STEAP) is expressed predominantly in human prostate
      tissue and in other common malignancies including prostate, bladder, colon, and
      ovarian carcinomas, and in Ewing's sarcoma, suggesting that it could function as
      an almost universal tumor antigen. We have used MHC peptide binding algorithms to
      predict potential STEAP sequences capable of stimulating in vitro naive HLA-A2
      restricted CTLs. Four of six peptides predicted by these algorithms were able to
      induce antigen-specific CTLs that killed peptide-pulsed HLA-A2 target cells. Two
      of these peptides, STEAP-292 (MIAVFLPIV) and a modification of this peptide STEAP
      292.2L (MLAVFLPIV), were the most efficient in the induction of primary CTL
      responses. More importantly, these CTLs were able to respond to tumor cells that
      express HLA-A2 and STEAP (colon, bladder, prostate, Ewing's sarcoma, and
      melanoma). Our results provide strong evidence that STEAP-292 is naturally
      processed by many tumor types and is presented in the context of HLA-A2 in
      sufficient amounts to allow recognition by CTLs. Also because STEAP-292.2L is a
      more immunogenic peptide able to induce CTL recognition of these STEAP-containing
      tumors and may have potential as an antitumor peptide vaccine.

PMID- 15958641
TI  - Oncolytic viral therapy for cervical and ovarian cancer cells by Sindbis virus
      AR339 strain.
AB  - PURPOSE: Recently, the application of replication-competent viruses has been
      studied as anticancer agents. Sindbis virus (SIN) is an RNA virus that belongs to
      the Alphavirus genus in the Togaviridae virus family. The AR339 strain of SIN has
      not been reported to induce any serious disease to humans. EXPERIMENTAL DESIGN:
      In this study, we evaluated the feasibility of the replication-competent SIN
      AR339 strain as an agent for cervical and ovarian cancer therapy. RESULTS: SIN
      infection was able to induce cytopathic effects and apoptosis in two cervical
      cancer cells (HeLaS3 and C33A) and three ovarian cancer cells (HOC-1, HAC-2, and
      OMC-3) but not in normal human keratinocytes in vitro. The analysis of cell
      viability, virus protein synthesis, and viral growth showed the cancer-specific
      cytotoxicity and virus growth of SIN. In nude mice, i.t. and i.v. inoculation of
      SIN resulted in significant regression of established cervical tumors implanted
      at their backs. Histologic studies revealed that systemic treatment with the
      single injection of SIN induces necrosis within tumors at a remote site. In the
      metastasis model of ovarian cancer, suppression of ascites formation was observed
      in nude mice with i.p. SIN treatment. By using an in vivo green fluorescent
      protein imaging system, we also showed that systemic treatment with SIN targeted
      tumors specifically. CONCLUSIONS: Our study suggested that SIN AR339 strain has a
      possibility as a novel agent for human cervical and ovarian cancer therapy.

PMID- 15958642
TI  - Low levels of Her2/neu expressed by Ewing's family tumor cell lines can redirect
      cytokine-induced killer cells.
AB  - PURPOSE: To identify novel treatments for pediatric solid tumors and/or for
      malignancies with low-level Her2/neu expression. EXPERIMENTAL DESIGN: Using
      fluorescence-activated cell sorting and immunohistochemistry, Her2/neu expression
      was determined on cell lines derived vfrom Ewing's family tumors (EFT) and
      neuroblastoma. Sensitivity to trastuzumab treatment was investigated using an in
      vitro proliferation assay. Cytotoxicity against EFT cell lines was done with
      either freshly isolated or ex vivo activated and expanded T cells (cytokine
      induced killer cells, CIK cells), with or without addition of a CD3xHer2/neu
      bispecific antibody. The effects of either trastuzumab, CIK cells alone, or
      CD3xHer2/neu bispecific antibody redirected CIK cells was determined using a
      SCID/hu model of EFTs and serial, noninvasive bioluminescent imaging. RESULTS:
      EFT cell lines express 5- to 10-fold lower levels of her2/neu than either breast
      (BT-474) or ovarian (SK-OV-3) cell lines. Treatment of EFT cell lines with
      trastuzumab did not induce growth inhibition either in vitro or in vivo. In
      contrast, Her2/neu could be used to redirect CIK cell to mediate cytotoxicity
      against EFTs both in vitro and in vivo (using two different treatment schemas).
      CONCLUSIONS: CD3xHer2/neu bispecific antibody and CIK cells may be a suitable
      approach to treat malignancies with low-level Her2/neu expression not responsive
      to trastuzumab.

PMID- 15958643
TI  - Enhancement of in vitro and in vivo tumor cell radiosensitivity by the DNA
      methylation inhibitor zebularine.
AB  - Aberrant DNA hypermethylation is a frequent finding in tumor cells, which has
      suggested that inhibition of DNA methylation may be an effective cancer treatment
      strategy. Because DNA methylation affects gene expression and chromatin
      structure, parameters considered to influence radioresponse, we investigated the
      effects of the DNA methylation inhibitor zebularine on the radiosensitivity of
      human tumor cells. Three human tumor cell lines were used in this study (MiaPaCa,
      DU145, and U251) and the methylation status of three genes frequently
      hypermethylated in tumor cells (RASSF1A, HIC-1, and 14-3-3sigma) was determined
      as a function of zebularine exposure. Zebularine resulted in DNA demethylation in
      a time-dependent manner, with the maximum loss of methylation detected by 48
      hours. Treatment of cells with zebularine for 48 hours also resulted in an
      increase in radiosensitivity with dose enhancement factors of >1.5. As a measure
      of radiation-induced DNA damage, gammaH2AX expression was determined. Whereas
      zebularine had no effect on radiation-induced gammaH2AX foci at 1 hour, the
      number of gammaH2AX foci per cell was significantly greater in the zebularine
      treated cells at 24 hours after irradiation, suggesting the presence of
      unrepaired DNA damage. Zebularine administration to mice reactivated gene
      expression in U251 xenografts; irradiation of U251 tumors in mice treated with
      zebularine resulted in an increase in radiation-induced tumor growth delay. These
      results indicate that zebularine can enhance tumor cell radiosensitivity in vitro
      and in vivo and suggest that this effect may involve an inhibition of DNA repair.

PMID- 15958644
TI  - Activation of p53-dependent apoptosis by acute ablation of glycogen synthase
      kinase-3beta in colorectal cancer cells.
AB  - PURPOSE: The restoration of checkpoint mechanisms may provide a rational
      anticancer approach, but the molecular circuitries of how this can be achieved
      therapeutically are poorly understood. A pivotal signaling network in colorectal
      cancer cells involves glycogen synthase kinase-3beta (GSK3beta), a
      multifunctional kinase whose role in tumor cell survival is not defined.
      EXPERIMENTAL DESIGN: We used molecular, genetic, and pharmacologic antagonists of
      GSK3beta in p53+/+ or p53-/- colorectal cancer cells. We monitored kinase
      activity in immunoprecipitation, protein expression by immunoblotting, and cell
      death by multiparametric flow cytometry. A xenograft colorectal cancer model was
      used to study antitumor activity in vivo. RESULTS: Treatment of p53+/+ colorectal
      cancer cells with pharmacologic inhibitors of GSK3beta resulted in sustained
      elevation of p53, with up-regulation of p21(Waf1/Cip1) and loss of survivin
      levels. Molecular targeting of GSK3beta by overexpression of a GSK3beta dominant
      negative mutant, or acute-silencing of GSK3beta by RNA interference, reproduced
      the induction of transcriptionally active p53 in colorectal cancer cells. This
      pathway was recapitulated by deregulated Wnt/T-cell factor signaling, with
      elevation of the tumor suppressor p14ARF, and reduced expression of the p53
      antagonist, MDM2. Rather than cell cycle arrest, GSK3beta blockade resulted in
      p53-dependent apoptosis, which was contributed by acute loss of survivin and
      inhibition of colorectal cancer growth in mice. CONCLUSIONS: Acute ablation of
      GSK3beta in colorectal cancer cells activates p53-dependent apoptosis and
      antagonizes tumor growth. This pathway may be exploited for rational treatment of
      colorectal cancer patients retaining wild-type p53.

PMID- 15958645
TI  - The farnesyltransferase inhibitor L744832 potentiates UCN-01-induced apoptosis in
      human multiple myeloma cells.
AB  - PURPOSE: The purpose of this study was to characterize interactions between the
      farnesyltransferase inhibitor L744832 and the checkpoint abrogator UCN-01 in drug
      sensitive and drug-resistant human myeloma cell lines and primary CD138+ multiple
      myeloma cells. EXPERIMENTAL DESIGN: Wild-type and drug-resistant myeloma cell
      lines were exposed to UCN-01 +/- L744832 for 24 hours, after which mitochondrial
      injury, caspase activation, apoptosis, and various perturbations in signaling and
      survival pathways were monitored. RESULTS: Simultaneous exposure of myeloma cells
      to marginally toxic concentrations of L744832 and UCN-01 resulted in a
      synergistic induction of mitochondrial damage, caspase activation, and apoptosis,
      associated with activation of p34cdc2 and c-Jun-NH2-kinase and inactivation of
      extracellular signal-regulated kinase, Akt, GSK-3, p70(S6K), and signal
      transducers and activators of transcription 3 (STAT3). Enhanced lethality for the
      combination was also observed in primary CD138+ myeloma cells, but not in their
      CD138- counterparts. L744832/UCN-01-mediated lethality was not attenuated by
      conventional resistance mechanisms to cytotoxic drugs (e.g., melphalan or
      dexamethasone), addition of exogenous interleukin-6 or insulin-like growth factor
      I, or the presence of stromal cells. In contrast, enforced activation of STAT3
      significantly protected myeloma cells from L744832/UCN-01-induced apoptosis.
      CONCLUSIONS: Coadministration of the farnesyltransferase inhibitor L744832
      promotes UCN-01-induced apoptosis in human multiple myeloma cells through a
      process that may involve perturbations in various survival signaling pathways,
      including extracellular signal-regulated kinase, Akt, and STAT3, and through a
      process capable of circumventing conventional modes of myeloma cell resistance,
      including growth factor- and stromal cell-related mechanisms. They also raise the
      possibility that combined treatment with farnesyltransferase inhibitors and UCN
      01 could represent a novel therapeutic strategy in multiple myeloma.

PMID- 15958646
TI  - Systemic treatment with tetra-O-methyl nordihydroguaiaretic acid suppresses the
      growth of human xenograft tumors.
AB  - PURPOSE: We have previously shown that the transcriptional inhibitor tetra-O
      methyl nordihydroguaiaretic acid (M4N) induces growth arrest in tumor cells and
      exhibits tumoricidal activity when injected intratumorally into tumor cell
      explants in mice. The experiments reported here were designed to determine
      whether M(4)N can be given systemically and inhibit the growth of five different
      human xenograft tumors. EXPERIMENTAL DESIGN: Nude (nu/nu) mice bearing xenografts
      of each of five human tumor types (i.e., hepatocellular carcinoma, Hep 3B;
      prostate carcinoma, LNCaP; colorectal carcinoma, HT-29; breast carcinoma, MCF7;
      and erythroleukemia, K-562) were treated with M4N given i.v. or i.p. in a
      Cremophor EL-based solvent system or orally in a corn oil based diet. Tumors from
      the treated animals were measured weekly and analyzed for the expression of the
      Cdc2 and survivin genes, both previously shown to be down-regulated by M4N.
      RESULTS: Systemic M4N treatment suppressed the in vivo growth of xenografts in
      each of the five human tumor types. Four of the five tumor models were
      particularly sensitive to M4N with tumor growth inhibitions (T/C values) of < or
      = 42%, whereas the fifth, HT-29, responded to a lesser extent (48.3%). Growth
      arrest and apoptosis in both the xenograft tumors and in the tumor cells grown in
      culture were accompanied by reductions in both Cdc2 and tumor-specific survivin
      gene expression. Pharmacokinetic analysis following oral and i.v. administration
      to ICR mice indicated an absolute bioavailability for oral M4N of approximately
      88%. Minimal drug-related toxicity was observed. CONCLUSION: These preclinical
      studies establish that when given systemically, M4N can safely and effectively
      inhibit the growth of human tumors in nude mice.

PMID- 15958647
TI  - The transforming growth factor-beta family members bone morphogenetic protein-2
      and macrophage inhibitory cytokine-1 as mediators of the antiangiogenic activity
      of N-(4-hydroxyphenyl)retinamide.
AB  - PURPOSE: Tumor growth appears to be an angiogenesis-dependent process. N-(4
      hydroxyphenyl)retinamide (fenretinide; 4HPR) has been found to inhibit and/or
      prevent tumor growth under diverse conditions. Although 4HPR is antiangiogenic,
      the molecular mechanisms of this effect remain largely unknown. EXPERIMENTAL
      DESIGN: Endothelial cells were treated with 4HPR in vitro to study the effects on
      migration, invasion, and organization, as well as gene expression by microarray
      and quantitative PCR studies. In vivo angiogenesis was evaluated in the Matrigel
      model. RESULTS: 4HPR treatment substantially modified the biological activities
      of endothelial cells, repressing their capacity to migrate, invade, and organize
      into capillary-like structures. The inhibition of invasion induced by 4HPR was
      also associated with decreased activities of the metalloproteases matrix
      metalloproteinase-2 and CD13/APN. Using oligonucleotide microarrays, we observed
      that bone morphogenetic protein-2 and macrophage inhibitory cytokine-1, two
      multifunctional cytokines of the transforming growth factor-beta family that
      regulate the growth, differentiation, apoptosis, and matrix accumulation of a
      variety of cells, are up-regulated in vitro by 4HPR. Both these molecules
      specifically inhibited endothelial cell growth, migration, and invasion in vitro
      and suppressed angiogenesis in the Matrigel plug assay in vivo. Blocking
      antibodies to bone morphogenetic protein-2 were able to reverse the suppressive
      effects of 4HPR in vitro and in vivo. CONCLUSIONS: These data support the
      conclusion that 4HPR inhibits tumor growth by repression of new vessel growth and
      identify novel points of regulation of angiogenesis in transforming growth factor
      beta family proteins.

PMID- 15958648
TI  - Genetic polymorphisms of selected DNA repair genes, estrogen and progesterone
      receptor status, and breast cancer risk.
AB  - PURPOSE: Genetic polymorphisms of DNA repair genes seem to determine the DNA
      repair capacity, which in turn may affect the risk of breast cancer. To evaluate
      the role of genetic polymorphisms of DNA repair genes in breast cancer, we
      conducted a hospital-based case-control study of Korean women. EXPERIMENTAL
      DESIGN: We included 872 incident breast cancer cases and 671 controls recruited
      from several teaching hospitals in Seoul from 1995 to 2002. Twelve loci of
      selected DNA repair genes were genotyped by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (XRCC2 Arg188His, XRCC4
      921G > T, XRCC6 1796G > T, LIG4 1977T/C, RAD51 135G > C, 172G > T, RAD52 2259C >
      T, LIG1 551A > C, ERCC1 8092A > C, 354C > T, hMLH1 -93G > A, and Ile219Val).
      RESULTS: We found that the RAD52 2259 CT or TT, hMLH1 -93 GG, and ERCC1 8092 AA
      genotypes were associated with breast cancer risk after adjustment for known risk
      factors [odds ratio (OR), 1.33; 95% confidence interval (95% CI), 1.02-1.75; OR,
      1.31; 95% CI, 0.99-1.74; and OR, 0.58; 95% CI, 0.38-0.89, respectively]. When
      Bonferroni's method was used to correct for multiple comparisons for nine
      polymorphisms with P = 0.005, all of these associations were not significant.
      However, the effects of RAD52 2259 CT or TT and ERCC1 354 CT or TT genotypes were
      more evident for the estrogen/progesterone receptor-negative cases (OR, 2.03; 95%
      CI, 1.24-3.34 and OR, 1.99; 95% CI, 1.35-2.94, respectively). CONCLUSION: Our
      findings suggest that genetic polymorphisms of RAD52, ERCC1, and hMLH1 may be
      associated with breast cancer risk in Korean women.

PMID- 15958649
TI  - Effects of dosing condition on the oral bioavailability of green tea catechins
      after single-dose administration of Polyphenon E in healthy individuals.
AB  - PURPOSE: Green tea has been shown to exhibit cancer-preventive activities in
      preclinical studies. Its consumption has been associated with decreased risk of
      certain types of cancers in humans. The oral bioavailability of the major green
      tea constituents, green tea catechins, is low, resulting in systemic catechin
      levels in humans many fold less than the effective concentrations determined in
      in vitro systems. We conducted this clinical study to test the hypothesis that
      the oral bioavailability of green tea catechins can be enhanced when consumed in
      the absence of food. EXPERIMENTAL DESIGNS: Thirty healthy volunteers were
      randomly assigned to one of the following doses of Polyphenon E (a decaffeinated
      and defined green tea catechin mixture): 400, 800, or 1,200 mg, based on the
      epigallocatechin gallate content (10 subjects per dose group). After an overnight
      fast, study participants took a single dose of Polyphenon E with or without a
      light breakfast, which consisted of one or two 4-oz muffins and a glass of water.
      Following a 1-week wash-out period, subjects were crossed over to take the same
      dose of Polyphenon E under the opposite fasting/fed condition. Tea catechin
      concentrations in plasma and urine samples collected after dosing were determined
      by high-pressure liquid chromatography analysis. RESULTS: Consistent with
      previous reports, epigallocatechin gallate and epicatechin gallate were present
      in plasma mostly as the free form, whereas epicatechin and epigallocatechin were
      mostly present as the glucuronide and sulfate conjugates. There was >3.5-fold
      increase in the average maximum plasma concentration of free epigallocatechin
      gallate when Polyphenon E was taken in the fasting condition than when taken with
      food. The dosing condition led to a similar change in plasma-free
      epigallocatechin and epicatechin gallate levels. Taking Polyphenon E in the
      fasting state did not have a significant effect on the plasma levels of total
      (free and conjugated) epigallocatechin, but resulted in lower plasma levels of
      total epicatechin. Urinary epigallocatechin gallate and epicatechin gallate
      levels were very low or undetectable following Polyphenon E administration with
      either dosing condition. Taking Polyphenon E under the fasting state resulted in
      a significant decrease in the urinary recovery of total epigallocatechin and
      epicatechin. Polyphenon E administered as a single dose over the dose range
      studied was generally well-tolerated by the study participants. Mild and
      transient nausea was noted in some of the study participants and was seen most
      often at the highest study agent dose (1,200 mg epigallocatechin gallate) and in
      the fasting condition. CONCLUSIONS: We conclude that greater oral bioavailability
      of free catechins can be achieved by taking the Polyphenon E capsules on an empty
      stomach after an overnight fast. Polyphenon E up to a dose that contains 800 mg
      epigallocatechin gallate is well-tolerated when taken under the fasting
      condition. This dosing condition is also expected to optimize the biological
      effects of tea catechins.

PMID- 15958650
TI  - Researchers should have respect for the originator of the cell lines.

PMID- 15958652
TI  - Increased cathepsin D release by Hyp mouse osteoblast cells.
AB  - The X-linked hypophosphatemia (XLH), the most common form of hereditary rickets,
      is caused by loss-of-function mutations of PHEX (phosphate-regulating gene with
      homology to endopeptidases on the X chromosome) leading to rachitic bone disease
      and hypophosphatemia. Available evidence today indicates that the bone defect in
      XLH is caused not only by hypophosphatemia and altered vitamin D metabolism but
      also by factor(s) locally released by osteoblast cells (ObCs). The identity of
      these ObC-derived pathogenic factors remains unclear. In our present study, we
      report our finding of a prominent protein in the culture media derived from ObC
      of the hypophosphatemic (Hyp) mice, a murine homolog of human XLH, which was
      identified as the murine procathepsin D (Cat D). By metabolic labeling studies,
      we further confirmed that Hyp mouse ObCs released greater amount of Cat D into
      culture media. This increased Cat D release by Hyp mouse ObCs was unlikely to be
      due to nonspecific cell damage or heterogeneous cell population and was found to
      be associated with an increased Cat D expression at the protein level, possibly
      due to a reduced Cat D degradation. However, we were not able to detect a direct
      effect of PHEX protein on Cat D cleavage. In support of the involvement of Cat D
      in mediating the inhibitory effect of Hyp mouse ObC-conditioned media on ObC
      calcification, we found that exposure to Cat D inhibited ObC (45)Ca incorporation
      and that inhibition of Cat D abolished the inhibitory effect of Hyp mouse
      conditioned media on ObC calcification. In conclusion, results from our present
      study showed that Hyp mouse ObCs release a greater amount of Cat D, which may
      contribute to the inhibitory effect of Hyp mouse ObC-conditioned media on ObC
      mineralization.

PMID- 15958653
TI  - Expression of metallothoinein isoform 3 is restricted at the post-transcriptional
      level in human bladder epithelial cells.
AB  - This study was designed to define the effect that overexpression of MT-3 would
      have on a cell culture model of bladder urothelium. Stable and inducible
      transfection was used to achieve overexpression of the MT-3 gene in the UROtsa
      cell line. When the UROtsa cells were stably transfected with the MT-3 coding
      sequence, there was highly elevated expression of MT-3 mRNA, but no MT-3 protein.
      An inducible vector showed that low basal levels of MT-3 mRNA and protein could
      be produced, but that induction only increased MT-3 mRNA and not protein. The
      clones expressing low basal levels of MT-3 protein also had reduced growth rates
      compared to control cells. Site directed mutagenesis was used to produce an MT-3
      coding sequence where the prolines in positions 7 and 9 were converted to
      threonines. When this altered MT-3 was stably transfected into the UROtsa cells,
      the cells were able to accumulate the mutated form of the MT-3 protein. These
      studies show that MT-3 protein expression is inhibited by post-transcriptional
      control in the urothelial cell. Modifying the MT-3 protein to resemble the MT-1
      isoform removes this component of post-transcriptional control and allows
      accumulation of the mutated MT-3 protein. The altered sequence involved in post
      transcriptional control of MT-3 protein expression is the same sequence
      implicated in the neuronal growth inhibitory activity associated specifically
      with the MT-3 isoform of the MT gene family.

PMID- 15958655
TI  - Effects of methylmercury on primary brain cells in mono- and co-culture.
AB  - We report on the uptake of MeHg in astrocytes and neurons, as well as specific
      indicators of neurotoxicity. Cerebellar granule neurons and astrocytes separately
      and in co-culture were cultured in the presence of MeHg and changes in 3-[4, 5
      dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide (MTT)-reduction, lactate
      dehydrogenase (LDH) leakage, and cellular content of glutathione and amino acids
      were used as indicators of MeHg toxicity. Mitochondria in cortical astrocytes
      were slightly more sensitive than those in cerebellar astrocytes to the toxic
      effects of MeHg; furthermore, cellular integrity was better preserved in
      cerebellar astrocytes. When neurons and astrocytes from cerebellum were incubated
      in separable co-cultures using inserts, the astrocytes showed cellular damage at
      lower exposure to MeHg while neurons showed less changes compared to respective
      cell types in mono-cultures. Mercury uptake studies at 25 microM MeHg (10% serum
      present) showed that for neurons in co-culture the uptake was 1/3 compared to
      mono-cultures. In contrast, for astrocytes in co-culture, uptake was increased by
      75%. A MeHg concentration-dependent increase of glutamate content in mono
      cultures was noted. When MeHg concentration was increased to 10, 25, or 50
      microM, neurons in co-cultures decreased their glutamate content, whereas
      astrocytes showed an increase. Other amino acids, such as glutamine, serine,
      valine, isoleucine, taurine, and phenylalanine were unaffected by MeHg.
      Glutathione content showed MeHg concentration-dependent changes in astrocytes and
      was increased in neurons in co-culture incubated with 5 microM MeHg. In
      conclusion, astrocytes appear to increase neuronal resistance, indicating a
      possible protective role for astrocytes in MeHg neurotoxicity.

PMID- 15958654
TI  - Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit
      low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in
      most vertebrates. However, frogs are relatively insensitive to TCDD toxicity,
      especially during early life stages. Toxicity of TCDD and related halogenated
      aromatic hydrocarbons is mediated by the aryl hydrocarbon receptor (AhR), and
      specific differences in properties of the AhR signaling pathway can underlie in
      TCDD toxicity in different species. This study investigated the role of AhR in
      frog TCDD insensitivity, using Xenopus laevis as a model system. X. laevis, a
      pseudotetraploid species, expresses two distinct AhR1 genes, AhR1alpha and
      AhR1beta. Sharing 86% amino acid identity, these likely represent distinct genes,
      both orthologous to mammalian AhR and paralogous to the AhR2 gene(s) in most
      fish. Both AhR1alpha and AhR1beta exhibit TCDD-dependent binding of cognate DNA
      sequences, but they bind TCDD with at least 20-fold lower affinity than the mouse
      AhR(b-1) protein, and they are similarly less responsive in TCDD-induced reporter
      gene induction in conjunction with the mouse CYP1A1 promoter. Furthermore, CYP1A6
      and CYP1A7 induction by TCDD in cultured X. laevis A6 cells appears much less
      responsive than CYP1A induction in cell lines derived from more sensitive
      animals. Taken together, these data suggest that low affinity binding by X.
      laevis AhRs plays an important mechanistic role in the insensitivity of frogs to
      TCDD. An understanding of these molecular mechanisms should aid amphibian
      ecotoxicology and refine the use of frog embryos as a model [e.g. in FETAX (Frog
      Embryo Teratogenesis Assay-Xenopus)] for determining developmental toxicity of
      samples containing dioxin-like compounds.

PMID- 15958656
TI  - Attenuation of hyperoxic lung injury by the CYP1A inducer beta-naphthoflavone.
AB  - Supplemental oxygen, frequently used in premature infants, has been implicated in
      the development of bronchopulmonary dysplasia (BPD). While the mechanisms of
      oxygen-induced lung injury are not known, reactive oxygen species (ROS) are most
      likely involved in the process. Here, we tested the hypothesis that upregulation
      of cytochrome P450 (CYP) 1A isoforms in lung and liver may lead to protection
      against hyperoxic lung injury. Adult male Sprague-Dawley rats were pretreated
      with the CYP1A inducer beta-naphthoflavone (beta-NF) (80 mg/kg/day), once daily
      for 4 days, followed by exposure to hyperoxic environment (O2 > 95%) or room air
      (normoxia) for 60 h. Pleural effusions were measured as estimates of lung injury.
      Activities of hepatic and pulmonary CYP1A1 were determined by measurement of
      ethoxyresorufin O-deethylation (EROD) activity. Northern hybridization and
      Western blot analysis of lung and liver were performed to assess mRNA and protein
      levels, respectively. Our results showed that beta-NF-treated animals, which
      displayed the highest pulmonary and hepatic induction in EROD activity (10-fold
      and 8-fold increase over corn oil (CO) controls, respectively), offered the most
      protective effect against hyperoxic lung injury, p < 0.05. Northern and Western
      blot analysis correlated well with enzyme activities. Our results showed an
      inverse correlation between pulmonary and hepatic CYP1A expression and the extent
      of lung injury, which supports the hypothesis that CYP1A enzyme plays a
      protective role against oxygen-mediated tissue damage.

PMID- 15958657
TI  - Modulation of murine host response to enteric reovirus infection by the
      trichothecene deoxynivalenol.
AB  - Based on the known capacity of deoxynivalenol (DON) to target gut lymphoid tissue
      and IgA production, it was hypothesized that this mycotoxin interferes with the
      immune response to enteric reovirus infection. When mice were orally gavaged,
      first with 25 mg/kg bw DON, and then with reovirus serotype 1, strain Lang (T1/L)
      2 or 12 h later, viral titers in the GI tract were 10-fold higher than control
      mice after 5 days. Virus was almost completely cleared in both treatment and
      control groups from intestinal tissue after 10 days. Real-time PCR indicated
      that, in infected control mice, reovirus lambda2 core spike (L2 gene) RNA per g
      feces in infected mice that were pretreated with DON was significantly higher at
      1, 3, and 5 days than in infected mice only. In reovirus-infected mice, DON at
      doses of 10 and 25 mg/kg bw but not 2 and 5 mg/kg bw increased fecal L2 RNA,
      whereas DON doses as low as 2 mg/kg potentiated L2 RNA levels in Peyer's patches
      (PP). Reovirus-specific IgA levels in feces of mice treated with DON were
      significantly elevated, as were specific IgA responses in lamina propria and PP
      fragment cultures. Similar effects were observed for serum IgA and IgG. DON
      suppressed IFN-gamma responses in PP to reovirus at 3 and 5 days as compared to
      infected controls, while IL-2 mRNA concentrations were unaffected. Although
      reovirus alone did not induce Th2 cytokine mRNAs in PP, DON exposure
      significantly elevated IL-4, IL-6, and IL-10 mRNA expression at various times
      during the infection. ELISPOT revealed that mRNA expression data corresponded to
      suppression of IFN-gamma- and enhancement of IL-4-producing cell responses in PP
      cultures from DON-treated mice. Taken together, these data suggest that DON
      transiently increased both severity of the reovirus infection and shedding in
      feces as well as elevated reovirus IgA responses. These effects corresponded to
      suppressed Th1 and enhanced Th2 cytokine expression.

PMID- 15958658
TI  - The effects of methylmercury on mitochondrial function and reactive oxygen
      species formation in rat striatal synaptosomes are age-dependent.
AB  - Methylmercury (MeHg) is especially toxic to the developing central nervous
      system. In order to understand the reasons for this age-dependent vulnerability,
      we compared the effects of MeHg on formation of reactive oxygen species (ROS) and
      mitochondrial function in striatal synaptosomes obtained from rats of various
      ages. Basal ROS levels were greater, and basal mitochondrial function was lower,
      in synaptosomes from younger animals, compared to adult animals. MeHg induced ROS
      formation in synaptosomes from rats of all ages, although the increases were
      greatest in synaptosomes from the younger animals. MeHg also reduced
      mitochondrial metabolic function, as assessed by MTT reduction, as well as
      mitochondrial membrane potential; again, the greatest changes were seen in
      synaptosomes from early postnatal animals. These age-dependent differences in
      susceptibility to MeHg are most likely due to a less efficient ROS detoxifying
      system and lower activity of mitochondrial enzymes in tissue from young animals.

PMID- 15958659
TI  - Inflammatory and cytotoxic responses in mouse lungs exposed to purified toxins
      from building isolated Penicillium brevicompactum Dierckx and P. chrysogenum
      Thom.
AB  - In vitro and in vivo studies have shown that building-associated Penicillium
      spores and spore extracts can induce significant inflammatory responses in lung
      cells and animal models of lung disease. However, because spores and spore
      extracts comprise mixtures of bioactive constituents often including toxins, it
      is impossible to resolve which constituent mediates inflammatory responses. This
      study examined dose-response (0.5 nM, 2.5 nM, 5.0 nM, 12.5 nM/g body weight (BW)
      animal) and time-course (3, 6, 24 and 48 h post instillation (PI)) relationships
      associated with inflammatory and cytotoxic responses in mouse lungs
      intratracheally instilled with pure brevianamide A, mycophenolic acid, and
      roquefortine C. High doses (5.0 nM and/or 12.5 nM/g BW animal) of brevianamide A
      and mycophenolic acid, the dominant metabolites of P. brevicompactum, and
      roquefortine C, the dominant metabolite of P. chrysogenum, induced significant
      inflammatory responses within 6 h PI, expressed as differentially elevated
      macrophage, neutrophil, MIP-2, TNF, and IL-6 concentrations in the
      bronchioalveolar lavage fluid (BALF) of intratracheally exposed mice. Macrophage
      and neutrophil numbers were maximal at 24 h PI; responses of the other
      inflammatory markers were maximal at 6 h PI. Except for macrophage numbers in
      mycophenolic acid-treatment animals, cells exhibited significant dose-dependent
      like responses; for the chemo-/cytokine markers, dose dependency was lacking
      except for MIP-2 concentration in brevianamide A-treatment animals. It was also
      found that brevianamide A induced cytotoxicity expressed as significantly
      increased LDH concentration in mouse BALF, at concentrations of 12.5 nM/g BW
      animal and at 6 and 24 h PI. Albumin concentrations, measured as a nonspecific
      marker of vascular leakage, were significantly elevated in the BALF of mice
      treated with 12.5 nM/g nM brevianamide A/animal from 6 to 24 h PI and in > or
      =5.0 nM/g mycophenolic acid-treated animals at 6 to 24 h PI. These results
      suggest that these three toxins from Penicillium species common on damp materials
      in residential housing provoke compound-specific toxic responses with different
      toxicokinetics. Moreover, that these toxins can stimulate significant
      inflammatory responses in vivo might help explain some of the indoor effects
      associated with Penicillium spore exposures in indoor environments.

PMID- 15958660
TI  - A commercial mixture of the brominated flame retardant pentabrominated diphenyl
      ether (DE-71) induces respiratory burst in human neutrophil granulocytes in
      vitro.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used brominated flame
      retardants (BFRs), which have become ubiquitous in the environment. This study
      investigates the effects of the pentabrominated diphenyl ether mixture, DE-71, on
      human neutrophil granulocytes in vitro. DE-71 enhanced production of reactive
      oxygen species (ROS) in a concentration-dependent manner measured as lucigenin
      amplified chemiluminescence. Octabrominated diphenyl ether (OBDE), decabrominated
      diphenyl ether (DBDE), and the non-brominated diphenyl ether did not induce ROS
      formation at the concentrations tested. DPI (4 microM), an inhibitor of the NADPH
      oxidase completely inhibited DE-71 induced ROS formation, highlighting a role for
      NADPH oxidase activation. The protein kinase C inhibitor BIM (0.25 microM) and
      the selective chelator of intracellular calcium, BAPTA-AM (5 microM), also
      inhibited NADPH oxidase activation, indicating a calcium-dependent activation of
      PKC. ROS formation was also inhibited by the tyrosine kinase inhibitor tyrphostin
      (1 microM), the phospholipase C inhibitor ET-18-OCH3 (5 microM), and the
      phosphatidylinositol-3 kinase inhibitor LY294002 (25 microM). Alterations in
      intracellular calcium were measured using fura-2/AM, and a significant increase
      was measured after exposure to DE-71 both with and without extracellular calcium.
      The tetra brominated compound BDE-47 also enhanced ROS formation in a
      concentration dependent manner. The combination of DE-71 with the bacteria
      derived N-formyl peptide fMLP and PCB153 induced an additive effect in the
      lucigenin assay. We suggest that tyrosine kinase mediated activation of PI3K
      could result in enhanced activation of calcium-dependent PKC by enhanced PLC
      activity, followed by intracellular calcium release leading to ROS formation in
      neutrophil granulocytes.

PMID- 15958661
TI  - Olfactory evaluation in children: application to the CHARGE syndrome.
AB  - OBJECTIVE: To find an efficient tool for testing olfactory function in children
      and use it to investigate a group of children with CHARGE (coloboma, congenital
      heart disease, choanal atresia, mental and growth retardation, genital anomalies,
      and ear malformations and hearing loss) syndrome. METHODS: We adapted for
      children an olfaction test that had just been validated in an adult French
      population and investigated a control group of 25 healthy children aged 6 to 13
      years. We then tested the olfactory capacity of a group of 14 children with
      CHARGE syndrome, aged 6 to 18 years. A questionnaire was completed with the
      parents about their children's feeding difficulties and their ability to
      recognize odors in everyday life. We recorded and scored the histories of feeding
      behavior anomalies, the visual and auditory status, and current intellectual
      levels. MRI of the olfactory tracts and bulbs was analyzed for 9 of 14 children.
      RESULTS: We showed that healthy children have similar olfactory function to that
      of the adult control group, which was representative of the general population,
      without any difference for either gender or age. We also showed that all children
      with CHARGE syndrome had olfactory deficiency. Half of them were anosmic, and the
      others had olfactory residual function (hyposmic). We found no association
      between olfactory deficiency and feeding behavior, visual or auditory impairment,
      or intellectual level. Parental subjective evaluations were accurate for only
      half of the group. All of the MRIs showed anomalies of the olfactory tracts and
      bulbs varying from moderate hypoplasia to complete aplasia, without any relation
      between the radiologic and the functional results. CONCLUSIONS: Olfaction can be
      assessed in children, even the young and disabled. Our results support the
      proposition that rhinencephalon anomalies should be included as a major criterion
      for the diagnosis of CHARGE syndrome.

PMID- 15958662
TI  - Effects of the State Children's Health Insurance Program Expansions on children
      with chronic health conditions.
AB  - OBJECTIVE: To estimate the effects of the State Children's Health Insurance
      Program (SCHIP) expansions on insurance coverage, use of health care services,
      and access to care for children with chronic health conditions. METHODS: The
      primary source of data was the National Health Interview Survey. Children with
      chronic health conditions were identified primarily through reported diagnoses of
      common chronic conditions (eg, asthma, attention-deficit disorder, mental
      retardation, Down syndrome, cerebral palsy, muscular dystrophy, sickle cell
      disease, diabetes, arthritis, heart disease) and on the presence of activity
      limitations caused by a health problem lasting at least 12 months. We examined
      changes in a broad array of outcomes for children with chronic health conditions
      who gained eligibility under SCHIP or who were already eligible for coverage
      under Medicaid, comparing the periods before and after implementation of the
      program. Changes for these treatment groups were compared with children with
      slightly higher incomes, who should not have been affected by the eligibility
      expansions. Comparisons were made with adjustment for child, family, and other
      characteristics that might have independent effects on the outcomes of interest.
      Outcomes included health insurance coverage, use of general and specialty
      services, access to care, and out-of-pocket spending on health care. Selected
      analyses were conducted for children not identified as having chronic health
      conditions. RESULTS: The SCHIP expansions resulted in a 9.8 percentage point
      increase in the proportion of children with chronic conditions reporting public
      insurance and a 6.4 percentage point decline in the proportion uninsured. Unmet
      need for health care decreased by 8 percentage points, with most of the decline
      found for dental care. Increases in specialist, eye care, and dental visits and
      decreases in out-of-pocket spending and emergency-department and mental health
      visits were observed but did not meet standards of statistical significance.
      Estimated reductions in unmet need were greater for children with chronic
      conditions than for other children. CONCLUSIONS: Recent expansions in public
      insurance eligibility under SCHIP have improved coverage for children with
      chronic conditions, with selected improvements in access to care. However, some
      eligible children with chronic conditions remain uninsured, and the impact on
      access to care and service use were limited. Additional progress may require
      targeted outreach to children with chronic conditions and improvements in
      Medicaid and SCHIP service-delivery systems. Given the current fiscal environment
      and the fact that children with chronic conditions have not generally been
      protected from cutbacks, the recent progress documented in this study may be
      reversed.

PMID- 15958663
TI  - The pediatrician workforce: current status and future prospects.
AB  - The effective and efficient delivery of children's health care depends on the
      pediatrician workforce. The number, composition, and distribution of
      pediatricians necessary to deliver this care have been the subject of long
      standing policy and professional debate. This technical report reviews current
      characteristics and recent trends in the pediatric workforce and couples the
      workforce to a conceptual model of improvement in children's health and well
      being. Important recent changes in the workforce include (1) the growth in the
      number of pediatricians in relation to the child population, (2) increased
      numbers of female pediatricians and their attainment of majority gender status in
      the specialty, (3) the persistence of a large number of international medical
      graduates entering training programs, (4) a lack of ethnic and racial diversity
      in pediatricians compared with children, and (5) the persistence of marked
      regional variation in pediatrician supply. Supply models projecting the pediatric
      workforce are reviewed and generally indicate that the number of pediatricians
      per child will increase by 50% over the next 20 years. The differing methods of
      assessing workforce requirements are presented and critiqued. The report finds
      that the pediatric workforce is undergoing fundamental changes that will have
      important effects on the professional lives of pediatricians and children's
      health care delivery.

PMID- 15958664
TI  - Paramyxovirus mRNA editing, the "rule of six" and error catastrophe: a
      hypothesis.
AB  - The order Mononegavirales includes three virus families that replicate in the
      cytoplasm: the Paramyxoviridae, composed of two subfamilies, the Paramyxovirinae
      and Pneumovirinae, the Rhabdoviridae and the Filoviridae. These viruses, also
      called non-segmented negative-strand RNA viruses (NNV), contain five to ten
      tandemly linked genes, which are separated by conserved junctional sequences that
      act as mRNA start and poly(A)/stop sites. For the NNV, downstream mRNA synthesis
      depends on termination of the upstream mRNA, and all NNV RNA-dependent RNA
      polymerases reiteratively copy ("stutter" on) a short run of template uridylates
      during transcription to polyadenylate and terminate their mRNAs. The RNA
      dependent RNA polymerase of a subset of the NNV, all members of the
      Paramyxovirinae, also stutter in a very controlled fashion to edit their
      phosphoprotein gene mRNA, and Ebola virus, a filovirus, carries out a related
      process on its glycoprotein mRNA. Remarkably, all viruses that edit their
      phosphoprotein mRNA are also governed by the "rule of six", i.e. their genomes
      must be of polyhexameric length (6n+0) to replicate efficiently. Why these two
      seemingly unrelated processes are so tightly linked in the Paramyxovirinae has
      been an enigma. This paper will review what is presently known about these two
      processes that are unique to viruses of this subfamily, and will discuss whether
      this enigmatic linkage could be due to the phenomenon of RNA virus error
      catastrophe.

PMID- 15958665
TI  - Interaction between the respiratory syncytial virus G glycoprotein cytoplasmic
      domain and the matrix protein.
AB  - Paramyxovirus assembly at the cell membrane requires the movement of viral
      components to budding sites and envelopment of nucleocapsids by cellular
      membranes containing viral glycoproteins, facilitated by interactions with the
      matrix protein. The specific protein interactions during assembly of respiratory
      syncytial virus (RSV) are unknown. Here, the postulated interaction between the
      RSV matrix protein (M) and G glycoprotein (G) was investigated. Partial co
      localization of M with G was demonstrated, but not with a truncated variant
      lacking the cytoplasmic domain and one-third of the transmembrane domain, in
      cells infected with recombinant RSV or transfected to express G and M. A series
      of G mutants was constructed with progressively truncated or modified cytoplasmic
      domains. Data from co-expression in cells and a cell-free binding assay showed
      that the N-terminal aa 2-6 of G play a key role in G-M interaction, with serine
      at position 2 and aspartate at position 6 playing key roles.

PMID- 15958666
TI  - Novel mechanism of immunosuppression by influenza virus haemagglutinin: selective
      suppression of interleukin 12 p35 transcription in murine bone marrow-derived
      dendritic cells.
AB  - Infection with influenza virus strongly predisposes an individual to bacterial
      superinfection, which is often the significant cause of morbidity and mortality
      during influenza epidemics. Little is known about the immunomodulating properties
      of the virus that lead to this phenomenon, but the effect of the viral components
      on the development of immune dendritic cells (DCs) may prove vital. In this
      study, activation of and cytokine secretion by bacterial lipopolysaccharide (LPS)
      stimulated bone marrow-derived dendritic cells (BMDCs) following treatment with
      the influenza virus major antigen haemagglutinin (HA) were examined. HA
      selectively inhibits the release of LPS-induced interleukin 12 (IL12) p70, which
      is independent of IL10 secretion. Suppression occurs at the transcriptional
      level, with selective inhibition of p35- and not p40-subunit mRNA expression. The
      downregulation of IL12 p70 by influenza HA is a novel and unexplored pathway that
      may be relevant in the predisposition to bacterial superinfection associated with
      influenza virus infections.

PMID- 15958667
TI  - Identification of the Borna disease virus (BDV) proteins required for the
      formation of BDV-like particles.
AB  - Borna disease virus (BDV) is an enveloped virus with a non-segmented, negative
      strand RNA genome that has an organization characteristic of Mononegavirales.
      However, based on its unique genetics and biological features BDV is considered
      to be the prototypic member of a new virus family, Bornaviridae. Here, the use of
      a reverse genetic approach to identify the viral proteins required for packaging
      of BDV RNA analogues (MG) into infectious virus-like particles (VLPs) was
      described. Plasmids encoding individual BDV proteins under the control of a RNA
      polymerase II promoter were co-transfected with a plasmid that allows for
      intracellular synthesis of a BDV MG mediated by the cellular RNA polymerase I.
      Clarified lysates from transfected cells were passaged onto fresh cells that were
      previously transfected with plasmids expressing the minimal BDV trans-acting
      factors L, N and P required for RNA synthesis mediated by the BDV polymerase.
      Reconstitution of BDV MG-specific packaging and passage of infectious VLP was
      monitored by expression of the chloramphenicol acetyl transferase reporter gene
      present in the BDV MG. BDV M and G, in addition to L, N and P, were sufficient
      for the passage of chloramphenicol acetyl transferase activity, which could be
      blocked by BDV neutralizing antibodies to G, indicating that VLP infectivity was
      fully mediated by BDV G. Passage of BDV MG was abrogated by omission of either M
      or G.

PMID- 15958668
TI  - Tissue tropism of recombinant coxsackieviruses in an adult mouse model.
AB  - Recombinant viruses, constructed by exchanging the 5' non-coding region (5'NCR),
      structural and non-structural protein coding sequences were used to investigate
      determinants responsible for differences between coxsackievirus A9 (CAV9) and
      coxsackievirus B3 (CBV3) infections in adult mice and two cell lines. Plaque
      assay titration of recombinant and parental viruses from different tissues from
      adult BALB/c mice demonstrated that the structural region of CBV3 determined
      tropism to the liver tissue due to receptor recognition, and the 5'NCR of CBV3
      enhanced viral multiplication in the mouse pancreas. Infection with a chimeric
      virus, containing the structural region from CBV3 and the rest of the genome from
      CAV9, and the parental CBV3 strain, caused high levels of viraemia in adult mice.
      The ability of these viruses to infect the central nervous system suggested that
      neurotropism is associated with high replication levels and the presence of the
      CBV3 capsid proteins, which also enhanced formation of neutralizing antibodies.
      Moreover, the appearance of neutralizing antibodies correlated directly with the
      clearance of the viruses from the tissues. These results demonstrate potential
      pathogenicity of intraspecies recombinant coxsackieviruses, and the complexity of
      the genetic determinants underlying tissue tropism.

PMID- 15958669
TI  - Structure of Foot-and-mouth disease virus serotype A10 61 alone and complexed
      with oligosaccharide receptor: receptor conservation in the face of antigenic
      variation.
AB  - Foot-and-mouth disease viruses (FMDVs) target epithelial cells via integrin
      receptors, but can acquire the capacity to bind cell-surface heparan sulphate (or
      alternative receptors) on passage in cell culture. Vaccine viruses must be
      propagated in cell culture and, hence, some rationale for the selection of
      variants in this process is important. Crystal structures are available for type
      O, A and C viruses and also for a complex of type O strain O(1)BFS with heparin.
      The structure of FMDV A10(61) (a cell culture-adapted strain) complexed with
      heparin has now been determined. This virus has an RGSD motif in place of the
      otherwise conserved RGD integrin-binding motif and the potential to bind heparan
      sulphate (suggested by sequence analyses). FMDV A10(61) was closely similar in
      structure to other serotypes, deviating most in antigenic sites. The VP1 GH loop
      comprising the integrin-binding motif was disordered. Heparin bound at a similar
      site and in a similar conformation to that seen in the analogous complex with
      O(1)BFS, although the binding had a lower affinity and was more ionic.

PMID- 15958670
TI  - The 3a protein of severe acute respiratory syndrome-associated coronavirus
      induces apoptosis in Vero E6 cells.
AB  - An outbreak of severe acute respiratory syndrome (SARS) occurred in China and the
      first case emerged in mid-November 2002. The aetiological agent of this disease
      was found to be a previously unknown coronavirus, SARS-associated coronavirus
      (SARS-CoV). The detailed pathology of SARS-CoV infection and the host response to
      the viral infection are still not known. The 3a gene encodes a non-structural
      viral protein, which is predicted to be a transmembrane protein. In this study,
      it was shown that the 3a protein was expressed in the lungs and intestinal
      tissues of SARS patients and that the protein localized to the endoplasmic
      reticulum in 3a-transfected monkey kidney Vero E6 cells. In vitro experiments of
      chromatin condensation and DNA fragmentation suggested that the 3a protein may
      trigger apoptosis. These data showed that overexpression of a single SARS-CoV
      protein can induce apoptosis in vitro.

PMID- 15958671
TI  - Evolutionary dynamics of hepatitis C virus envelope genes during chronic
      infection.
AB  - Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are important targets
      for the host immune response. The genes encoding these proteins exhibit a high
      degree of variability that gives rise to differing phenotypic traits, including
      alterations in receptor-binding affinity and immune recognition and escape. In
      order to elucidate patterns of adaptive evolution during chronic infection, a
      panel of full-length E1E2 clones was generated from sequential serum samples
      obtained from four chronically infected individuals. By using likelihood-based
      methods for phylogenetic inference, the evolutionary dynamics of circulating HCV
      quasispecies populations were assessed and a site-by-site analysis of the
      d(N)/d(S) ratio was performed, to identify specific codons undergoing
      diversifying positive selection. HCV phylogenies, coupled with the number and
      distribution of selected sites, differed markedly between patients, highlighting
      that HCV evolution during chronic infection is a patient-specific phenomenon.
      This analysis shows that purifying selection is the major force acting on HCV
      populations in chronic infection. Whilst no significant evidence for positive
      selection was observed in E1, a number of sites under positive selection were
      identified within the ectodomain of the E2 protein. All of these sites were
      located in regions hypothesized to be exposed to the selective environment of the
      host, including a number of functionally defined domains that have been reported
      to be involved in immune evasion and receptor binding. Dated-tip methods for
      estimation of underlying HCV mutation rates were also applied to the data,
      enabling prediction of the most recent common ancestor for each patient's
      quasispecies.

PMID- 15958672
TI  - Immune responses of pigs after experimental infection with a European strain of
      Porcine reproductive and respiratory syndrome virus.
AB  - The purpose of this experiment was to study the immune response of pigs during an
      experimental infection with a European strain of Porcine reproductive and
      respiratory syndrome virus (PRRSV). Five pigs were challenged intranasally with
      PRRSV strain VP21 and another five were kept as controls. Clinical course and
      humoral and cell-mediated responses were monitored for 70 days post-infection
      (p.i.). Infected pigs developed mild signs at 24 h p.i. Viraemia was detectable
      by nested RT-PCR until day 14 p.i. Earliest seroconversions (ELISA) were seen by
      day 7 p.i. (three of five animals) and, by day 14, all inoculated pigs had
      seroconverted (ELISA and immunoperoxidase monolayer assay). Virus-neutralizing
      antibodies were undetectable until day 56 p.i. and, by day 70 p.i., two
      inoculated pigs still were negative. Flow-cytometry assays using peripheral blood
      mononuclear cells (PBMC) showed an upshift in CD8(+) cells (day 7 p.i.) and a
      downshift of CD21(+) cells (days 7 and 28 p.i.). Regarding cell-mediated
      responses, development of PRRSV-specific gamma interferon-secreting cells (IFN
      gamma-SC) and interleukin 4-secreting cells (IL4-SC) in PBMC was examined by
      ELISPOT assay. IFN-gamma-SC were not detected significantly until day 14 p.i.,
      whereas, for IL4-SC, no differences between groups were seen. Concurrently with
      the onset of viraemia and the development of clinical signs, serum haptoglobin
      levels and interleukin 10 (IL10) in PRRSV-stimulated PBMC-culture supernatants
      increased significantly. These differences disappeared later on. For IL2, IL4,
      IL8 or transforming growth factor beta, no differences were seen among groups.
      These results are compatible with a model in which the immune response does not
      fully control the outcome of the infection.

PMID- 15958673
TI  - Full-genome analysis of a highly divergent simian T-cell lymphotropic virus type
      1 strain in Macaca arctoides.
AB  - Full-genome sequencing and analysis of the highly divergent simian T-cell
      lymphotropic virus type 1 (STLV-1) strain MarB43 in Macaca arctoides indicated
      that its open reading frame structure is compatible with proper functioning of
      its Gag, Pol, Env, Tax and Rex proteins. Detailed analysis of the coding
      potential, however, revealed that MarB43 is probably forced to use the human T
      cell lymphotropic virus type 2/STLV-2 env-tax-rex splice-acceptor homologue and
      that the proximal pX auxiliary proteins p12(I), p13(II), p30(II) and p27(I) seem
      to have lost their function. Full-genome (gag-pol-env-tax), long terminal repeat
      and env phylogenetic analyses conclusively identified STLV-1 in M. arctoides as
      the currently most divergent STLV-1 strain. The long branching pattern of the
      monophyletic STLV-1 Macaca subspecies clades suggests that macaques might be the
      ancestral reservoir for primate T-cell lymphotropic virus type 1 in Asia. Full
      genome molecular-clock analysis supports an archaic introduction of STLV-1 on the
      Asian continent, at least 269 000-156 000 years ago.

PMID- 15958674
TI  - Human immunodeficiency virus 1 (HIV-1) envelope-dependent cell-cell fusion
      modulation by HIV-positive sera is related to disease progression.
AB  - Fusion of CD4+ cells by HIV-1 envelope proteins (Env) is a mechanism of virus
      spread and cell damage. Production of antibodies able to influence cell-cell
      fusion in vivo may affect the course of the infection. The effect of sera from 49
      HIV-1-positive patients was tested on an in vitro fusion assay using Env
      expressing and normal Jurkat T cells labelled with DiI and DiO dyes, and flow
      cytometry for quantification of cell-cell fusion. Sera varied in their activity
      on fusion: 69.4 % inhibited, 24.5 % had no effect and 6.1 % enhanced cell fusion.
      Fusion activity correlated positively with the CD4+ T-cell count and inversely
      with the viral load. Removal of IgG or IgM from sera reduced or eliminated
      inhibition and enhancing activities, respectively. Antibodies with inhibitory
      activity predominate in early and intermediate stages of infection, whereas loss
      of inhibition or enhancement of fusion correlates with progression to AIDS.

PMID- 15958675
TI  - A novel simian immunodeficiency virus from black mangabey (Lophocebus aterrimus)
      in the Democratic Republic of Congo.
AB  - In order to understand primate lentivirus evolution, characterization of
      additional simian immunodeficiency virus (SIV) strains is essential. Here, an SIV
      from a black mangabey (Lophocebus aterrimus) originating from the Democratic
      Republic of Congo was analysed phylogenetically. The monkey had cross-reactive
      antibodies against human immunodeficiency virus type 1 (HIV-1) and HIV-2. The
      viral pol region sequence was amplified by nested PCR and sequence analysis
      confirmed that it was related to known SIV sequences. This is the first report to
      characterize genetically an SIV from the monkey genus Lophocebus. Phylogenetic
      analysis of the pol region revealed that this novel SIV, designated SIVbkm, fell
      into the SIVsyk and SIVgsn virus group, containing viruses isolated from the
      genus Cercopithecus, and suggests that cross-species transmission has occurred
      between species of the genera Lophocebus and Cercopithecus.

PMID- 15958676
TI  - An approach for genogrouping of Japanese isolates of aquabirnaviruses in a new
      genogroup, VII, based on the VP2/NS junction region.
AB  - Aquabirnaviruses, represented by Infectious pancreatic necrosis virus (IPNV),
      have been isolated from epizootics in salmonids and a variety of aquatic animals
      in the world; six genogroups of aquabirnaviruses have been identified. In
      comparisons of nucleotide sequences of the VP2/NS junction region, maximum
      nucleotide diversities of 30.8 % were observed among 93 worldwide aquabirnavirus
      isolates. A phylogenetic tree revealed the existence of a new genogroup, VII, for
      Japanese aquabirnavirus isolates from marine fish and molluscan shellfish.
      Nucleotide diversities between genogroups VII and I-VI were 18.7 % or greater. At
      the nucleotide level, Japanese IPNV isolates from epizootics in salmonids were
      nearly identical to a genogroup I strain from the USA or Canada. It is suggested
      that Japanese IPNV isolates belonging to genogroup I were originally introduced
      from North American sources, whereas Japanese aquabirnavirus isolates of
      genogroup VII were from marine aquatic animals indigenous to Japan.

PMID- 15958677
TI  - US3 protein kinase of herpes simplex virus type 2 is required for the stability
      of the UL46-encoded tegument protein and its association with virus particles.
AB  - The herpes simplex virus (HSV) US3 gene encodes a serine/threonine protein kinase
      (PK). Although US3 PK is not essential for virus replication in cell culture, it
      plays an important role in the regulation of apoptosis in infected cells.
      However, the role of US3 PK in virus replication and pathogenicity is not well
      understood. The UL46 gene encodes virion tegument phosphoproteins, the properties
      and functions of which are poorly understood. In this study, it is shown that the
      UL46 protein of HSV type 2 (HSV-2) is affected strikingly by the presence of US3
      PK. In the absence of US3 PK, UL46 protein was quite unstable, being much more
      susceptible to degradation. UL46 protein was undetectable in the extracellular
      virions of US3-deficient virus. Moreover, in vitro kinase assays using
      recombinant US3 PK show that UL46 protein is phosphorylated by the US3 PK,
      suggesting that UL46 can be a direct substrate for US3 PK in infected cells.
      Together, these findings shed new light on the physiological functions of US3 PK.

PMID- 15958678
TI  - Analysis of a bovine herpesvirus 1 recombinant virus that does not express the
      bICP0 protein.
AB  - Bovine herpesvirus 1 (BHV-1) infected-cell protein 0 (bICP0) stimulates
      productive infection by activating viral gene expression. In this study, an
      attempt was made to construct a recombinant virus with point mutations in the
      C(3)HC(4) zinc RING finger of bICP0, as this domain is necessary for activating
      viral transcription and productive infection. A virus was identified in bovine
      cells that induced small clusters of infected cells resembling a small plaque.
      Instead of the expected mutations within the zinc RING finger, this virus
      contained a point mutation within the initiating ATG of bICP0, a point mutation
      two bases downstream from the ATG mutation and deletion of flanking plasmid
      sequences used for homologous recombination. The bICP0 mutant was rescued with
      wild-type (wt) bICP0 sequences and the bICP0-rescued virus produced wt plaques.
      The bICP0-rescued virus and wt BHV-1, but not the mutant, expressed the bICP0
      protein during productive infection of bovine cells, suggesting that the mutant
      virus was a null mutant. Consequently, the mutant was designated the bICP0 null
      mutant. Infection of bovine cells with the bICP0 null mutant resulted in at least
      100-fold lower virus titres, indicating that bICP0 protein expression is
      important, but not required, for virus production. When bovine cells infected
      with the bICP0 null mutant virus were subcultured, the cells continued to divide,
      but viral DNA could be detected after more than 35 passages, suggesting that the
      bICP0 null mutant induced a persistent-like infection in bovine cells and that it
      may be useful for generating additional bICP0 mutants.

PMID- 15958679
TI  - Inactivation of the viral interleukin 1beta receptor improves CD8+ T-cell memory
      responses elicited upon immunization with modified vaccinia virus Ankara.
AB  - Interleukin 1 (IL1) is an important regulator of inflammatory responses and
      contributes to host immune defence against infection. Vaccinia virus encodes a
      viral soluble IL1beta receptor (IL1betaR), which modulates the acute-phase host
      response to infection and might influence the induction of immune responses
      against virus-associated antigens. Here, modified vaccinia virus Ankara (MVA)
      mutants defective in IL1betaR production were produced by insertion of selectable
      marker gene sequences that precisely deleted the IL1betaR coding sequences from
      the MVA genome (MVA-DeltaIL1betaR). Analysis of MVA mutants indicated that
      deletion of the IL1betaR gene did not abrogate the formation of MVA progeny upon
      tissue culture propagation. After high-dose intranasal infection with MVA
      DeltaIL1betaR, mice showed no signs of fever or other illness, suggesting that
      the avirulent phenotype remained preserved for MVA-DeltaIL1betaR. Following
      vaccination of mice, MVA-DeltaIL1betaR or non-mutated MVA induced similar acute
      phase immune responses. Importantly, when monitored at the memory phase,
      significantly higher vaccinia virus-specific total CD8(+) and HLA-A*0201-binding
      peptide epitope-specific T-cell responses were found after vaccination of HLA
      A*0201-transgenic and non-transgenic mice with MVA-DeltaIL1betaR. Moreover, 4-6
      months after vaccination, MVA-DeltaIL1betaR provided higher levels of protection
      against lethal respiratory challenge infection with virulent vaccinia virus
      strain Western Reserve compared with wild-type MVA. These data suggest that
      deletion of the viral IL1betaR gene may be considered a relevant approach to
      amplify the virus-specific CD8+ memory T-cell response and duration of protective
      immunity obtained after MVA vaccination.

PMID- 15958680
TI  - Mousepox conjunctivitis: the role of Fas/FasL-mediated apoptosis of epithelial
      cells in virus dissemination.
AB  - BALB/c mice infected with the Moscow strain of Ectromelia virus (ECTV-MOS) show a
      large number of apoptotic cells, and an influx of lymphoid cells in the
      epithelium and substantia propria of conjunctivae, respectively. The presence of
      ECTV-MOS antigens in the epithelium of conjunctivae significantly upregulates Fas
      in the epithelial layer and FasL in the suprabasal layer of conjunctiva.
      Inhibition of FasL with blocking antibodies in cultures of conjunctival cells
      isolated from ECTV-MOS-infected BALB/c mice showed that the Fas/FasL pathway is
      important in apoptosis of ECTV-MOS-infected cells. The results also showed that
      the presence of cytokines, in particular interferon (IFN)-gamma, upregulated
      expression of Fas. Interleukin (IL) 2, 4, 10 and IFN-gamma were produced at the
      peak of conjunctivitis (at day 15 of infection) with a predominance of IFN-gamma
      and a small, but significant, production of IL4 and IL10 compared with non
      infected animals. These results suggest that not only is Fas/FasL expression in
      conjunctiva involved in elimination of migrating Fas+ cells but also plays an
      important role in the turnover of conjunctival epithelium and thus may be crucial
      for ECTV spreading to the surrounding environment.

PMID- 15958681
TI  - Deletion of open reading frames 9, 10 and 11 from the avian adenovirus CELO
      genome: effect on biodistribution and humoral responses.
AB  - In this study, the in vivo effect of the 3.6 kbp deletion of the three open
      reading frames (ORF) 9, 10 and 11 found at the right end of the CELO genome was
      examined. Groups of chickens were inoculated oronasally with 10(5)-10(7) p.f.u.
      per animal of wild-type virus and two recombinant CELO strains (rCELO) expressing
      luciferase and secreted alkaline phosphatase (SEAP). The tissue biodistribution,
      assessed by PCR, was similar for both wild-type and recombinant viruses. The
      infectious viral particle titre was determined by a p.f.u. counting method and
      the antibody responses to the CELO vector and the SEAP antigen were evaluated by
      ELISA. Infectious particle titres in tissues from chickens inoculated with the
      wild-type CELO virus increased up to 6 days post-inoculation, and declined until
      11 days while titres in organs from chickens inoculated with the rCELO strain
      were low and only detectable at 4 days post-inoculation. Moreover, although anti
      CELO antibody levels were three times lower in sera from chickens inoculated with
      rCELO, antibodies directed to the heterologous SEAP antigen were detected. Based
      on these results, no differences in tropism were observed, but the level of
      production of viral particles and the humoral responses appeared to decrease.
      Viruses replicate less efficiently with a deletion performed at the right end of
      the CELO genome. Nevertheless, the presence of antibodies directed to
      heterologous antigens makes the CELO virus an advantageous candidate for avian
      vaccination.

PMID- 15958682
TI  - Isolation and cloning of the raccoon (Procyon lotor) papillomavirus type 1 by
      using degenerate papillomavirus-specific primers.
AB  - Partial sequences of a novel papillomavirus were amplified from a cutaneous
      lesion biopsy of a raccoon (Procyon lotor), by using PCR with degenerate
      papillomavirus-specific primers. The Procyon lotor papillomavirus type 1 (PlPV-1)
      DNA was amplified with long template PCR in two overlapping fragments, together
      encompassing the entire genome, and the complete PlPV-1 genomic sequence was
      determined. The PlPV-1 genome consists of 8170 bp, and contains the typical
      papillomaviral open reading frames, encoding five early proteins and two late
      capsid proteins. Besides the classical non-coding region (NCR1) between the end
      of L1 and the start of E6, PlPV-1 contains an additional non-coding region (NCR2)
      of 1065 bp between the early and late protein region, which has previously also
      been described for the canine oral papillomavirus (COPV) and the Felis domesticus
      papillomavirus (FdPV-1). Phylogenetic analysis places PlPV-1 together with COPV
      and FdPV-1 in a monophyletic branch which encompasses the Lambda papillomavirus
      genus.

PMID- 15958683
TI  - New sequence polymorphisms in the outer loops of the JC polyomavirus major capsid
      protein (VP1) possibly associated with progressive multifocal
      leukoencephalopathy.
AB  - JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML)
      in patients with decreased immune competence. To elucidate genetic changes in
      JCPyV associated with the pathogenesis of PML, multiple complete JCPyV DNA clones
      originating from the brains of three PML cases were established and sequenced.
      Although unique rearranged control regions occurred in all clones, a low level of
      nucleotide variation was also found in the coding region. In each case, a
      parental coding sequence was identified, from which variant coding sequences with
      nucleotide substitutions would have been generated. A comparison between the
      parental and variant coding sequences demonstrated that all 12 detected
      nucleotide substitutions gave rise to amino acid changes. Interestingly, seven of
      these changes were located in the surface loops of the major capsid protein
      (VP1). Finally, 16 reported VP1 sequences of PML-type JCPyV (i.e. derived from
      the brain or cerebrospinal fluid of PML patients) were compared with their
      genotypic prototypes, generated as consensus sequences of representative
      archetypal isolates belonging to the same genotypes; 13 VP1 proteins had amino
      acid changes in the surface loops. In contrast, VP1 proteins from isolates from
      the urine of immunocompetent and immunosuppressed patients rarely underwent
      mutations in the VP1 loops. The present findings suggest that PML-type JCPyV
      frequently undergoes amino acid substitutions in the VP1 loops. These
      polymorphisms should serve as a new marker for the identification of JCPyV
      isolates associated with PML. The biological significance of these mutations,
      however, remains unclear.

PMID- 15958684
TI  - A new subtype (subgenotype) Ac (A3) of hepatitis B virus and recombination
      between genotypes A and E in Cameroon.
AB  - Blood samples (n=544) from two different populations (Pygmies and Bantus) in
      Cameroon, West Africa, were analysed. Serological tests indicated that the anti
      hepatitis C virus (HCV) prevalence in Bantus (20.3 %) was higher than that in
      Pygmies (2.3 %, P<0.0001), whereas the distribution of hepatitis B virus (HBV)
      serological markers was equally high in both populations: in total, 9.4, 17.3 and
      86.8 % for HBsAg, anti-HBs and anti-HBc, respectively. HBV genotype A (HBV/A) and
      HBV/E were predominant (43.5 % each) in both populations, and HBV/D was found in
      a minority (13 %). The preS/S region was sequenced in nine cases (five HBV/A and
      four HBV/E) and the complete genome in six cases (four HBV/A and two HBV/E).
      Subsequent phylogenetic analysis revealed that the HBV/A strains were distinct
      from the subtypes (subgenotypes) described previously, Ae (A2) and Aa (A1), and
      in the preS/S region they clustered with previously reported sequences from
      Cameroon. Based on the nucleotide difference from Aa (A1) and Ae (A2), more than
      4 % in the complete genome, the Cameroonian strains were suggested to represent a
      new subtype (subgenotype), designated HBV/Ac (A3). A high (3.9 %) nucleotide
      divergence in HBV/Ac (A3) strains suggested that the subtype (subgenotype) has a
      long natural history in the population of Cameroon. One of the HBV/Ac (A3)
      strains was found to be a recombinant with an HBV/E-specific sequence in the
      polymerase reverse transcriptase domain. Further cohort studies will be required
      to assess detailed epidemiological, virological and clinical characteristics of
      HBV/Ac (A3), as well as its recombinant form.

PMID- 15958685
TI  - Binding and entry characteristics of porcine circovirus 2 in cells of the porcine
      monocytic line 3D4/31.
AB  - Porcine circovirus 2 (PCV2) is associated with post-weaning multisystemic wasting
      syndrome and reproductive problems in pigs. Cells of the monocyte/macrophage
      lineage are important target cells in PCV2-infected pigs, but the method of
      binding and entry of PCV2 into these cells is unknown. Therefore, binding and
      entry of PCV2 to the porcine monocytic cell line 3D4/31 were studied by
      visualization of binding and internalization of PCV2 virus-like particles (VLPs)
      by confocal microscopy and chemical inhibition of endocytic pathways (clathrin-
      and caveolae-mediated endocytosis and macropinocytosis), followed by evaluation
      of the level of PCV2 infection. It was shown that PCV2 VLPs bound to all cells,
      with maximal binding starting from 30 min post-incubation. Bound PCV2 VLPs were
      internalized in 47+/-5.0 % of cells. Internalization was continuous, with 70.5+/
      9.7 % of bound PCV2 VLPs internalized at 360 min post-incubation. Internalizing
      PCV2 VLPs co-localized with clathrin. PCV2 infection was decreased significantly
      by chemical inhibitors that specifically blocked (i) actin-dependent processes,
      including cytochalasin D (75.5+/-7.0 % reduction) and latrunculin B (71.0+/-3.0 %
      reduction), and (ii) clathrin-mediated endocytosis, including potassium depletion
      combined with hypotonic shock (50.2+/-6.3 % reduction), hypertonic medium (56.4+/
      5.7 % reduction), cytosol acidification (59.1+/-7.1 % reduction) and amantadine
      (52.6+/-6.7 % reduction). Inhibiting macropinocytosis with amiloride and caveolae
      dependent endocytosis with nystatin did not decrease PCV2 infection
      significantly. PCV2 infection was reduced by the lysosomotropic weak bases
      ammonium chloride (47.0+/-7.9 % reduction) and chloroquine diphosphate (49.0+/
      5.6 % reduction). Together, these data demonstrate that PCV2 enters 3D4/31 cells
      predominantly via clathrin-mediated endocytosis and requires an acidic
      environment for infection.

PMID- 15958686
TI  - Genome sequence of Chrysodeixis chalcites nucleopolyhedrovirus, a baculovirus
      with two DNA photolyase genes.
AB  - The complete genome sequence of a single nucleocapsid nucleopolyhedrovirus
      recently isolated from Chrysodeixis chalcites (ChchNPV) was determined. The viral
      genome has a size of 149 622 bp and an overall G+C content of 39.1 mol%. The
      sequence contains 151 predicted open reading frames (ORFs) with a minimal size of
      50 codons. The similarity of these ORFs with those of other completely sequenced
      baculoviruses was calculated using a newly developed database, named GECCO.
      Phylogenetic analysis of the whole genome confirmed the evolutionary relationship
      of ChchNPV with group II NPVs, as did the absence of the NPV group I-specific
      gp64 gene. It is the first group II NPV to encode proliferating cell nuclear
      antigen. Most noteworthy is the presence of two ORFs encoding a class II
      cyclobutane pyrimidine dimer DNA photolyase. These two ORFs share only 45 % amino
      acid identity and have different promoter motifs. Twenty-two additional unique
      baculovirus genes were identified, including a gene encoding a novel putative
      RING finger protein with a possible homologue in poxviruses.

PMID- 15958687
TI  - Gene-expression profiling of White spot syndrome virus in vivo.
AB  - White spot syndrome virus, type species of the genus Whispovirus in the family
      Nimaviridae, is a large, double-stranded DNA (dsDNA) virus that infects
      crustaceans. The genome of the completely sequenced isolate WSSV-TH encodes 184
      putative open reading frames (ORFs), the functions of which are largely unknown.
      To study the transcription of these ORFs, a DNA microarray was constructed,
      containing probes corresponding to nearly all putative WSSV-TH ORFs. Transcripts
      of 79 % of these ORFs could be detected in the gills of WSSV-infected shrimp
      (Penaeus monodon). Clustering of the transcription profiles of the individual
      genes during infection showed two major classes of genes: the first class reached
      maximal expression at 20 h post-infection (p.i.) (putative early) and the other
      class at 2 days p.i. (putative late). Nearly all major and minor structural
      virion-protein genes clustered in the latter group. These data provide evidence
      that, similar to other large, dsDNA viruses, the WSSV genes at large are
      expressed in a coordinated and cascaded fashion. Furthermore, the transcriptomes
      of the WSSV isolates WSSV-TH and TH-96-II, which have differential virulence,
      were compared at 2 days p.i. The TH-96-II genome encodes 10 ORFs that are not
      present in WSSV-TH, of which at least seven were expressed in P. monodon as well
      as in crayfish (Astacus leptodactylus), suggesting a functional but not essential
      role for these genes during infection. Expression levels of most other ORFs
      shared by both isolates were similar. Evaluation of transcription profiles by
      using a genome-wide approach provides a better understanding of WSSV
      transcription regulation and a new tool to study WSSV gene function.

PMID- 15958688
TI  - Characterization of Potato virus Y (PVY) molecular determinants involved in the
      vein necrosis symptom induced by PVYN isolates in infected Nicotiana tabacum cv.
      Xanthi.
AB  - Viral molecular determinant(s) involved in the tobacco vein necrosis (TVN)
      symptom induced by necrotic isolates of Potato virus Y (PVY) on Nicotiana tabacum
      cv. Xanthi leaves remain undetermined. Reference isolates belonging to PVY(N)
      (infectious PVY(N)-605 clone) and PVY(O) (PVY(O)-139) were used to produce PVY
      chimeric genomes by using reverse-genetic techniques. These chimeric clones were
      inoculated biolistically onto Nicotiana clevelandii plants to establish the
      clone, prior to being tested on N. tabacum for their ability to induce TVN
      symptoms. Comparison between sequence data and symptoms observed for each mutated
      PVY construct shows that the C-terminal part of the multifunctional HC-Pro
      protein includes two residues (K(400) and E(419)) that are involved in TVN
      induced by PVY(N) isolates. Site-directed mutagenesis was used to confirm that
      these two HC-Pro residues are involved in the TVN phenotype.

PMID- 15958689
TI  - Phage display-selected single-chain antibodies confer high levels of resistance
      against Tomato spotted wilt virus.
AB  - Rational design of antibodies targeting essential viral proteins can complement
      the palette of antiviral resistance strategies. Here, stable and high expression
      of single-chain monoclonal antibodies targeting the nucleoprotein of the
      economically important plant virus Tomato spotted wilt virus, a protein that is
      involved in multiple steps in the viral infection cycle, is reported. High
      cytoplasmic expression levels of three selected phage display-derived anti-viral
      single-chain antibodies were established. Of these antibodies, two led to high
      levels of resistance against this plant virus. Protoplast experiments provided
      evidence that the two resistance-conferring antibodies may have a different mode
      of action and could be combined for higher durability of resistance in the field.

PMID- 15958690
TI  - Functional characterization of the Beet necrotic yellow vein virus RNA-5-encoded
      p26 protein: evidence for structural pathogenicity determinants.
AB  - A Beet necrotic yellow vein virus isolate containing a fifth RNA is present in
      the Pithiviers area of France. A full-length cDNA clone of RNA-5 was obtained and
      placed under the control of a T(7)-RNA-pol promoter that allowed the production
      of infectious transcripts. "Pithiviers" isolate-specific necrotic symptoms were
      obtained on Chenopodium quinoa when RNA-5-encoded p26 was expressed either from
      RNA-5 or from an RNA-3-derived replicon. By using haemagglutinin- and green
      fluorescent protein-tagged constructs, virally expressed p26-fusion proteins
      induced the same necrotic local lesions on host plants and were localized mainly
      in the nucleus of infected cells. Deletion mutagenesis permitted identification
      of two domains, responsible respectively for nuclear export and cytoplasmic
      retention of the p26 mutated proteins. By using a yeast two-hybrid system, Gal4DB
      p26 protein self-activated transcription of the His3 reporter gene. The p26
      transcription-activation domain was located within its first 55 aa and has been
      studied by alanine scanning. Resulting p26 mutants were tested for their
      capability to induce necrotic symptoms and to localize in the nuclear
      compartment.

PMID- 15958691
TI  - Acute myeloid leukemia stem cells.
AB  - A fundamental problem in cancer research is identification of the cells within a
      tumor that sustain the growth of the neoplastic clone. The concept that only a
      subpopulation of rare cancer stem cells (CSCs) is responsible for maintenance of
      the neoplasm emerged nearly 50 years ago; however, conclusive proof for the
      existence of a CSC was obtained only relatively recently. The evidence for the
      existence of CSCs was first derived from the study of human acute myeloid
      leukemia (AML), largely because of the availability of quantitative stem cell
      assays for the leukemic stem cell (LSC). These studies showed that only rare
      cells within the leukemic clone had the capacity to initiate AML growth after
      transplant into NOD/SCID mice, establishing the hierarchical organization of AML.
      Recent clonal-tracking studies showed that the LSC compartment is composed of
      different classes of LSCs, which can be distinguished on the basis of self
      renewal potential. These findings have important implications for our
      understanding of the leukemogenic process as well as the design of more effective
      therapies to eliminate AML based on eradication of the LSCs. These studies are
      briefly reviewed here.

PMID- 15958692
TI  - Control of self-renewal and differentiation of hematopoietic stem cells: HOXB4 on
      the threshold.
AB  - The homeodomain transcription factor HOXB4 is one of the most attractive tools to
      expand hematopoietic stem cells in vitro and in vivo and to promote the formation
      of hematopoietic cells from in vitro differentiated embryonic stem cells.
      However, the expression levels compatible with the favorable effect of enhanced
      self-renewal without perturbing differentiation, in vivo, remain to be
      determined. In this paper, we discuss the necessity to define the "therapeutic
      width" of HOXB4 expression, based on observations from our lab and others that
      demonstrate that ectopic HOXB4 expression leads to a concentration-dependent
      perturbation of lineage differentiation of mouse and human hematopoietic cells.
      In summary, the combined results argue in favor of the existence of certain
      threshold levels for HOXB4 activity that control the differentiation and self
      renewal behavior of hematopoietic stem and progenitor cells. Indeed, existing
      evidence suggests that dosage effects of ectopically expressed transcription
      factors may be more the rule than an exception.

PMID- 15958693
TI  - Developmental impact of leukemic fusion genes on stem cell fate.
AB  - Stem and progenitor cells present attractive targets for transformation by
      leukemia-associated fusion genes generated by chromosomal translocation. The
      mechanism by which these fusion genes corrupt the transcriptional programs of
      these cellular compartments remains largely unknown. We have sought to gain
      insight into these issues through expressing TEL-AML1 and TEL-TRKC fusion genes
      in murine stem cells and recording effects on cell behavior in a transplant
      setting.

PMID- 15958694
TI  - Derivation of the hematopoietic stem cell compartment from human embryonic stem
      cell lines.
AB  - Since the derivation of human embryonic stem cell (hESC) lines, both experimental
      and clinical hematology have generated rising interest in differentiating
      functional hematopoietic progenitors from these pluripotent cell lines. Although
      the ability to generate primitive hematopoietic cells with in vivo reconstitution
      function has direct clinical application, success of this approach awaits a more
      in-depth understanding of factor and mechanisms that govern specification of
      pluripotent hESCs to hematopoietic lineage specification. Here, we highlight some
      of our laboratory's recent efforts in this area, in the hopes of providing
      insights toward this complex yet important area of biomedical research.

PMID- 15958695
TI  - Thrombopoietin regulates differentiation of rhesus monkey embryonic stem cells to
      hematopoietic cells.
AB  - Thrombopoietin (TPO) is the primary regulator of megakaryocyte and platelet
      production in vitro and in vivo. It supports also survival and proliferation of
      hematopoietic stem cells. The TPO receptor, c-mpl, is a member of the
      protooncogene family. Our studies focused on the effect of TPO on proliferation
      and differentiation of rhesus monkey embryonic stem cells to hematopoietic cells.
      The rationale of the present investigations was the finding that patients with
      congenital amegakaryocytic thrombocytopenia (CAMT) reveal c-mpl mutations leading
      to the development of pancytopenia, suggesting that c-mpl is expressed in early
      hematopoiesis. Here we demonstrate that rhesus monkey embryonic stem (ES) cells
      are capable of differentiating into uncommitted progenitor cells, including
      hemangioblasts (hematopoietic and endothelial precursor cells). The combination
      of TPO and vascular endothelial growth factor (VEGF) significantly increases the
      number of hemangioblasts and promotes even differentiation to CD34(+)
      hematopoietic progenitor cells (up to 8%). In addition, analysis of gene
      expression during hemangioblast development demonstrates that TPO is capable of
      increasing the mRNA expression of the VEGF receptor (VEGFR) and its own receptor
      (c-mpl). The in vitro differentiation of rhesus monkey ES cells provides an
      opportunity to better understand the mechanism of TPO function in the early stage
      of hematopoietic development from ES cells to mature hematopoietic cells.

PMID- 15958696
TI  - The vascular wall as a source of stem cells.
AB  - We have characterized the emerging hematopoietic system in the human embryo and
      fetus. Two embryonic organs, the yolk sac and aorta, support the primary
      emergence of hematopoietic stem cells (HSCs), but only the latter contributes
      lymphomyeloid stem cells for definitive, adult-type hematopoiesis. A common
      feature of intra- and extraembryonic hematopoiesis is that in both locations
      hematopoietic cells emerge in close vicinity to vascular endothelial cells. We
      have provided evidence that a population of angiohematopoietic mesodermal stem
      cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate
      from the paraaortic splanchnopleura into the ventral part of the aorta, where
      they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells.
      HSCs also appear to develop from endothelium in the embryonic liver and fetal
      bone marrow, albeit at a much lower frequency. This would imply that the organism
      does not function during its whole life on a stock of hematopoietic stem cells
      established in the early embryo, as is usually accepted. We next examined whether
      the vessel wall can contribute stem cells for other cell lineages, primarily in
      the model of adult skeletal muscle regeneration. By immunohistochemistry and flow
      cytometry, we documented the existence in skeletal muscle, besides genuine
      endothelial and myogenic cells, of a subset of satellite cells that coexpress
      endothelial cell markers. This suggested the existence of a continuum of
      differentiation from vascular cells to endothelial cells that was confirmed in
      long-term culture. The regenerating capacity of these cells expressing both
      myogenic and endothelial markers is being investigated in skeletal and cardiac
      muscle, and the results are being compared with those generated by satellite
      cells. Altogether, these results point to a generalized progenitor potential of a
      subset of endothelial, or endothelium-like, cells in blood vessel walls, in pre-
      and postnatal life.

PMID- 15958697
TI  - Genetic and functional characterization of isolated stromal cell lines from the
      aorta-gonado-mesonephros region.
AB  - The hematopoietic system interacts with a supportive stromal environment allowing
      maintenance and differentiation of hematopoietic stem cells (HSCs). The aorta
      gonado-mesonephros (AGM) region serves as a unique embryonic microenvironment,
      generating the first adult repopulating HSCs in the mouse embryo. To eludicate
      factors involved in hematopoietic support and induction of hematopoietic
      differentiation, we isolated more than 100 stromal cell clones derived from the
      AGM region of embryonic day (E) 10.5 mouse embryos for functional and genetic
      analysis. Selected isolated AGM stromal cell lines are highly efficient in
      supporting maintenance and expansion of mouse and human hematopoietic stem and
      progenitor cells. In addition, we can demonstrate for the first time that AGM
      stromal cell lines are also potent inducers of hematopoietic differentiation of
      murine embryonic stem cells. Stromal gene array analysis has identified genes
      that could play a role in hematopoietic support.

PMID- 15958698
TI  - Involvement of proteases in cytokine-induced hematopoietic stem cell
      mobilization.
AB  - The number of circulating stem cells and progenitor cells can be increased by
      physiological stress, such as exercise, stress, and infections. The process of
      shifting the stem cells from the bone marrow into the peripheral blood is
      referred to as "mobilization" or "egress." Cytokine-mobilized hematopoietic
      progenitor cells (HPCs) are currently used for autologous or allogeneic stem cell
      transplantation in a variety of malignant and nonmalignant diseases. In spite of
      the wide-spread use of mobilized peripheral blood stem cells for transplantation,
      the mechanisms underlying mobilization are still incompletely understood. Here we
      discuss the role of neutrophils and proteases as mediators of stem cell
      mobilization.

PMID- 15958699
TI  - Hematopoietic stem cell transplantation across major genetic barriers: tolerance
      induction by megadose CD34 cells and other veto cells.
AB  - Studies in mice and humans demonstrate that transplantation of hematopoietic
      progenitors in numbers larger than commonly used overcomes major genetic
      barriers. In vitro studies suggest that veto cells, within the population of
      hematopoietic progenitors, facilitate this favorable outcome. Tolerance induction
      can be further enhanced by other veto cells. Perhaps the most potent veto cell is
      the CD8(+) CTL. However, this cell is also associated with marked GVHD, which can
      be separated from the veto activity by generating anti-third party CTLs under IL
      2 deprivation.

PMID- 15958700
TI  - The role of sphingosine 1-phosphate receptors in the trafficking of hematopoietic
      progenitor cells.
AB  - Sphingosine 1-phosphate (S1P) is an ubiquitously present extracellular lipid
      mediator that is released by several cell types, particularly by activated
      platelets. The effects of S1P are mediated by a specific family of G protein
      coupled sphingosine 1-phosphate receptors (S1P1-S1P5). We demonstrate that S1P
      acts on hematopoietic progenitor cells as a chemotactic factor, attracting
      peripheral blood CD34(+) cells in vitro. Furthermore, constant activation of S1P
      receptors augments CXCR4-mediated signal transduction induced by stromal cell
      derived factor 1 (SDF-1). These effects are most likely mediated by the S1P1
      receptor consistently expressed in both primitive and committed CD34(+)
      hematopoietic progenitor cells (HPCs). In vivo, sustained activation of S1P1 by a
      receptor agonist during the homing process resulted in increased engraftment.
      Given the fact that activated platelets represent a major source of extracellular
      S1P, SDF-1-mediated stem cell homing may occur at sites of tissue injury in
      addition to the bone marrow. This could explain the previously observed
      contribution of primary hematopoietic stem cells to tissue repair in myocardial
      infarction and other diseases.

PMID- 15958701
TI  - Epigenetic regulation of normal and cancer stem cells.
AB  - In many tissues, a cellular hierarchy exists in which a small population of stem
      cells is responsible for the production of the mature cells of the organ. The
      stem cells maintain themselves through a process known as self-renewal.
      Similarly, tumors contain a minority population of cancer stem cells that
      maintain the tumor. Some factors that regulate this process of self-renewal are
      conserved from fruit fly to humans. Disruption of the regulation of self-renewal
      results in cancer. Thus understanding the mechanisms that regulate stem cell
      generation has implications for normal development and disease.

PMID- 15958702
TI  - Distinct gene expression pattern of malignant hematopoietic stem and progenitor
      cells in polycythemia vera.
AB  - Polycythemia vera (PV) is a chronic myeloproliferative disorder with an expansion
      of multipotent hematopoietic progenitor cells. Although it is known that
      hematopoietic progenitors in PV are erythropoietin independent and hypersensitive
      to several cytokines, the molecular oncogenic mechanisms in PV are largely
      unknown. In this study, we examined gene expression profiles of CD34(+) cells
      from bone marrow of patients with de novo PV and from healthy volunteers to
      identify molecular changes associated with the malignant growth of hematopoietic
      stem and progenitor cells in this myeloproliferative disorder. Using cDNA arrays,
      we found significant differences (P < .01) in the expression of 107 genes.
      Proapoptotic genes (CASP2, CASP3, DAPK1, ALG2) were expressed at lower levels in
      PV-CD34(+) cells, reflecting a lower apoptotic activity. Fibrosis-stimulating
      growth factors (transforming growth factor beta1, transforming growth factor
      beta2, bone morphogenetic protein 2, and endothelial growth factor) were
      expressed at significantly higher levels in PV-CD34(+) cells. Furthermore, PV
      CD34(+) cells overexpressed several receptors, protein kinases, and proteasome
      subunits, which might be targets for directed therapeutic approaches. It is
      interesting that three retinoid receptors were overexpressed in PV-CD34(+) cells-
      retinoic acid receptor beta (RARbeta), retinoid X receptor beta (RXRbeta), and
      cellular retinoic acid binding protein 2 (CRABP2). Using methylcellulose colony
      forming assays, we found that the formation of erythroid colonies derived from PV
      hematopoietic progenitors was inhibited by all-trans-retinoic acid (ATRA), a
      natural ligand of those receptors, in a dose-dependent manner, showing a maximum
      inhibition of 89% at 10 microM; the growth of myelomonocytic colonies was not
      significantly affected. These data suggest that the use of ATRA could be of
      therapeutic benefit for patients with PV.

PMID- 15958703
TI  - Hox genes: from leukemia to hematopoietic stem cell expansion.
AB  - Hox genes are clearly implicated in leukemia; however, neither the specificity of
      the leukemogenic potential among Hox genes of different paralog groups nor the
      role of the homeodomain is clear. We tested the leukemogenic potential of various
      NUP98-Hox fusion genes alone and with MEIS1. All genes tested had a significant
      overlapping effect in bone marrow cells in vitro. However, not all formed strong
      leukemogenic NUP98 fusion genes; but together with overexpression of MEIS1, all
      induced myeloid leukemia. This phenomenon was also seen with NUP98 fusions
      containing only the homeodomain of the corresponding Hox protein. We then
      exploited the strong transforming potential of NUP98-HOXD13 and NUP98-HOXA10 to
      establish preleukemic myeloid lines composed of early myeloid progenitors with
      extensive in vitro self-renewal capacity, short-term myeloid repopulating
      activity, and low propensity for spontaneous leukemic conversion. We also showed
      that MEIS1 can efficiently induce their conversion to leukemic stem cells, thus
      providing a novel model for the study of leukemic progression. In contrast to the
      leukemogenic effect of most of the Hox genes tested, HOXB4 has the ability to
      increase the self-renewal of hematopoietic stem cells without disrupting normal
      differentiation. On the basis of the discovery that the leukemogenic gene HOXA9
      can also expand hematopoietic stem cells, we compared the ability of NUP98-Hox
      fusions to that of HOXB4 to trigger HSC expansion in vitro. Our preliminary
      results indicate that the expanding potential of HOXB4 is retained and even
      augmented by fusion to NUP98. Moreover, even greater expansion may be possible
      using Abd-B-like Hox fusions genes.

PMID- 15958704
TI  - Engraftment of bone marrow-derived epithelial cells.
AB  - Discoveries of the ability of bone marrow-derived cells (BMDCs) to differentiate
      into nonhematopoietic cells have opened up a new field of inquiry in adult stem
      cell plasticity. There are far more questions than there are answers to date. We
      and others have investigated whether differentiation occurs in response to tissue
      damage, what the underlying mechanisms might be, and whether this plasticity may
      be useful clinically. BMDC have been shown to differentiate into mature-appearing
      epithelial cells in the lung, liver, gastrointestinal tract, skin, buccal mucosa,
      and kidney. The mechanism(s) by which cells transition to these nonhematopoietic
      phenotypes is not yet clear, but possibilities include cell-to-cell fusion,
      direct differentiation of a nonhematopoietic precursor cell from the BM, and
      transdifferentiation of a BM cell that had previously been committed to a
      different phenotype. Data obtained to date support the first two possibilities,
      and there are no data proving that transdifferentiation is responsible for the
      engraftment of marrow-derived epithelial cells. Theoretically, the engraftment of
      marrow-derived cells as nonhematopoietic cell types could be used in either the
      autologous or the allogeneic setting to restore functional epithelial cells to a
      diseased organ. For example, a marrow-derived cell that has been transduced to
      express a specific transgene can continue to express this transgene after it
      engrafts as a nonhematopoietic epithelial cell in the lung. Analyses of the
      kinetics of this engraftment suggest that it can be increased within days to
      weeks following certain types of injury, depending on the tissue examined. Most
      reports of adult stem cell plasticity show relatively low frequencies of marrow
      derived nonhematopoietic cells, on the order of 1 in 10(3) to 1 in 10(4)
      epithelial cells in many organs being marrow derived. This frequency is likely to
      be too low to be of therapeutic relevance. Therefore, future efforts will need to
      be focused on enhancing levels of engraftment.

PMID- 15958705
TI  - Lineage promiscuity and plasticity in hematopoietic development.
AB  - Hematopoiesis has provided a valuable model for understanding how genetic
      programs are established to decide cell fates in multipotent stem or progenitor
      cells. The identification of common myeloid and lymphoid progenitors has allowed
      us to directly assess the regulatory mechanisms of lineage commitment. Multiple
      genes of hematopoietic lineages, including transcription factors, are coexpressed
      in hematopoietic stem cells and progenitors, a phenomenon referred to as "lineage
      priming." The accessibility for multiple transcription factors promiscuously
      allows flexibility in cell fate commitments at the multipotent stages. The
      changes in the expression levels and timing of transcription factors can induce
      lineage conversion of committed cells, indicating that the regulation of
      transcription factors might be primarily critical for maintaining hierarchical
      hematopoietic development.

PMID- 15958706
TI  - Stem cell biology: a view toward the future.
AB  - In this essay I have attempted to provide clues relating to novel research
      avenues that are likely to have a broad impact on the field of stem cell biology.
      The specific examples, drawn from other areas, are meant to be instructive and
      are representative of many more similar efforts. I have suggested that the new
      areas of systems and synthetic biology may provide a truly deep level of
      understanding for many aspects of how stem cells make fate choices. Successful
      application of new avenues will require an integrative approach that combines
      experimental and computational techniques.

PMID- 15958707
TI  - Thrombopoietin and the hematopoietic stem cell.
AB  - The molecular mechanisms that underlie the favorable effects of thrombopoietin on
      stem cell survival, self-renewal, and expansion are unknown. On the basis of
      known effects of HoxB4, HoxA9, and vascular endothelial cell growth factor on
      stem cells, we explored whether TPO might affect these pathways. We found that
      TPO enhances the transcription of HoxB4, induces the nuclear localization of
      HoxA9, and upregulates VEGF expression by reducing the ubiquination of hypoxia
      inducible factor.

PMID- 15958708
TI  - Role of GATA-1 in normal and neoplastic hemopoiesis.
AB  - GATA-1 exerts a concentration-dependent control on the differentiation of
      erythroid, megakaryocytic, mast, and eosinophilic cells. The concentration of
      GATA-1 is, in turn, regulated by specific sequences within the GATA-1 locus. On
      the basis of its levels of expression, the GATA-1 protein becomes associated with
      suitable partners forming transcription complexes that, by binding to lineage
      specific enhancers, activate the expression of the corresponding target genes.
      Instrumental to our understanding of the role of GATA-1 in hemopoietic
      differentiation has been the generation of genetically engineered mutant mice and
      the discovery of naturally occurring mutations associated with either inherited
      or acquired human pathologies. We review our current understanding of the role of
      GATA-1 in normal and neoplastic hematopoiesis as emerging from these genetic
      approaches.

PMID- 15958709
TI  - Gene expression in stem cell-supporting stromal cell lines.
AB  - Cells in the immediate microenvironment together with hematopoietic stem cells
      (HSCs) constitute the stem cell niche. The microenvironmental or stromal cells
      provide a complex molecular milieu that helps mediate and balance the self
      renewal and commitment potentials of stem cells. The molecules in this milieu are
      not well defined. In this study, we have intersected previous cDNA subtraction
      studies with array expression methodologies to define and categorize known gene
      products expressed by HSC-supportive stromal cell lines. Data were curated from
      our previously released Stromal Cell Database (StroCDB) containing a set of gene
      products enriched for expression in the fetal liver stromal cell line AFT024.
      Global expression analyses were extended to other stem cell-supporting and 
      nonsupporting fetal liver stromal cell lines using commercially available
      microarrays. Known and previously described gene products from selected
      categories were studied: transcription factors, cell membrane proteins,
      cytoskeleton and related proteins, extracellular matrix proteins, cell adhesion
      molecules and their corresponding signaling molecules, and cytokines and their
      related mediators. More than 300 known gene products were selected for expression
      in HSC-supporting stromal cells compared to nonsupporting lines. Analyses of the
      data suggest that HSC-supportive cells are immature, sessile, and highly reactive
      after binding to integrin ligands and cytokines. Therefore, they provide a
      dynamic space poised to respond to molecular cues elaborated within the stem cell
      niche. The study provides a survey of known proteins that play key roles in the
      support of HSCs by fetal liver stromal cells. It also provides insights into the
      biology of the stem cell niche by highlighting the complex network of
      intercellular signaling and communication involved in the organization of the
      niche space.

PMID- 15958710
TI  - Effect of tyrosine kinase inhibition using imatinib on normal lymphohematopoietic
      cells.
AB  - Imatinib is a selective tyrosine kinase inhibitor used for the treatment of
      Philadelphia chromosome-positive leukemias and other malignancies. An important
      clinical observation is that imatinib can affect the function of normal
      nonmalignant cells resulting in myelosuppression in treated patients. This
      observation is supported by the recent findings suggesting that imatinib might
      affect mobilization, proliferation, and differentiation of hematopoietic
      progenitor cells while leaving hematopoietic stem cells unaffected. Furthermore,
      the induction of a specific T cell response seems to be impaired in chronic
      myeloid leukemia (CML) patients treated with imatinib in contrast to patients
      receiving interferon-alpha. Recent studies demonstrate that in vitro exposure of
      mobilized human CD34(+) progenitors to imatinib inhibits their differentiation
      into dendritic cells. This is of importance as some of the therapeutic effects in
      the treatment of patients with CML are mediated by the induction of leukemia
      specific T cell responses. Studies investigating the effects of imatinib on
      normal hematopoiesis are of interest because they might help us better understand
      the side effects observed clinically and might lead to the identification of
      novel therapeutic applications of the drug (e.g., in Bcr-Abl(-)
      myeloproliferative disorders and potentially as an immunomodulatory agent).

PMID- 15958711
TI  - Stem cell gene transfer: insights into integration and hematopoiesis from primate
      genetic marking studies.
AB  - Genetic marking strategies in the nonhuman primate model have elucidated a number
      of principles with relevance to implementation of clinical stem cell therapies,
      including the lineage potential, number, and life span of hematopoietic stem and
      progenitor cells. The recent occurrence of leukemias likely related to
      insertional activation of a proto-oncogene in two patients with X-severe combined
      immunodeficiency (SCID) syndromes treated with CD34(+) cells transduced with
      retroviral vectors expressing the corrective common gamma cytokine receptor gene
      has refocused attention on the issue of retroviral integration. We have analyzed
      >1500 independent insertions from rhesus macaques transplanted with CD34(+) cells
      transduced with either MLV or SIV vectors. Of these, 46 rhesus macaques followed
      long term have not had progression to leukemia, abnormal hematopoiesis, or clonal
      hematopoiesis. However, the pattern of both MLV and SIV integrants in cells of
      these animals was found to be highly nonrandom, with a propensity for insertions
      of both vectors within genes: for MLV particularly near the transcription start
      site, and for SIV particularly in gene-dense regions.

PMID- 15958712
TI  - Clonal multilineage differentiation of murine common pluripotent stem cells
      isolated from skeletal muscle and adipose stromal cells.
AB  - Pluripotent stem cells (PSCs) with transdifferentiation capacity may provide
      useful therapeutic modalities in the areas of cellular restoration and
      regenerative medicine. The utility of PSCs depends on their ability to respond to
      different stimuli and to adapt to tissue-specific differentiation conditions.
      Given that a number of cells possessing characteristics of PSCs have been
      identified and isolated from several adult murine tissues, we hypothesized that a
      common PSC may exist in multiple murine tissues and that these cells may either
      reside permanently in specific sites or continue to circulate and colonize
      tissues as needed. Previous data from our laboratory suggest that PSCs exhibiting
      an immunophenotype of CD45(-)Sca-1(+)c-kit(-)Thy-1(+) can be isolated from
      multiple murine tissues and may represent putative common PSCs (CoPSCs). To
      investigate whether the multiple tissue differentiation potential observed with
      these cells resulted from the presence of different tissue-restricted progenitors
      within CD45(-)Sca-1(+)c-kit(-)Thy-1(+) cells or was the product of clonal
      differentiation of CoPSCs, clonality studies were performed. Single skeletal
      muscle (SM)-derived CoPSCs were expanded for 10 days, and progeny cells were
      split into three culture conditions designed to stimulate myogenic, adipogenic,
      and neurogenic differentiation. Analysis of 600 clones indicated that 2.16%,
      0.83%, and 0.33% of the total number of plated single cells were capable of
      unipotent, bipotent, and tripotent differentiation, respectively, into
      combinations of myocytes, adipocytes, and neuronal cells. Given that SM-derived
      CoPSCs represent 4.78% of the total cells analyzed, tripotent CoPSCs made up
      0.016% of the total muscle cells. Similar results were obtained in clonal
      analyses using adipose stromal cell (ASC)-derived CoPSCs, suggesting that both SM
      and ASC-derived CoPSCs may be phenotypically and functionally identical. Taken
      together, these data demonstrate that a common PSC can be identified in different
      murine tissues and suggest that a small fraction of these cells are capable of
      clonal differentiation into multiple cell types.

PMID- 15958713
TI  - Tracking hematopoiesis at the single cell level.
AB  - Despite intensive research, many longstanding questions of experimental
      hematology remain unsolved. One major reason is the fact that hematopoiesis is
      usually followed by analyzing populations of cells rather than individual cells,
      at few points in time during an experiment and without knowing (or quickly
      loosing) the cells' individual identities. The static picture yielded by this
      approach makes it impossible to appreciate the dynamic developmental processes
      leading to the generation of the full hematopoietic system from individual
      hematopoietic stem cells (HSCs). Real-time tracking of individual cells in
      culture, tissues, or whole organisms would be an extremely powerful approach to
      fully understand the developmental complexity of hematopoiesis. To this end, a
      computer-aided culture and bioimaging system is being developed to follow the
      fate of individual cells over long periods of time. This system is used to follow
      the development of multilineage cobblestone colonies from adult HSCs in stroma
      cocultures at the single cell level over many generations. To facilitate
      noninvasive detection of lineage commitment in these cultures, new subcellular
      forms of optimized fluorescent proteins have been developed to allow simultaneous
      marking of multiple hematopoietic lineages within the same animal.

PMID- 15958715
TI  - Role of telomerase in hematopoietic stem cells.
AB  - Studies in hematopoietic stem cell (HSC) biology are often focused on "self
      renewal" and differentiation. Implicit in the word self-renewal is that the two
      daughter cells generated by a self-renewal division are identical to the parental
      cell. Strictly speaking, this is not possible because DNA is continuously damaged
      and repaired by DNA-repair mechanisms that are not 100% efficient. It is
      important to note that the efficiency of DNA repair varies greatly among
      different stem cell types. For example, embryonic stem cells are quite resistant
      to DNA damage and maintain the length of telomere repeats on serial passage,
      whereas HSCs are quite sensitive to DNA damage and less able to maintain telomere
      length. Most likely, differences between stem cell types in DNA repair and
      telomere maintenance pathways coevolved with cell mass, turnover, reproductive
      strategy, and life span. This idea has given rise to the notion that many aspects
      of normal aging could primarily reflect limitations in DNA repair and telomere
      maintenance pathways in the (stem) cells of the soma. In humans, levels of
      telomerase in HSCs are under extremely tight control, as is illustrated by the
      marrow failure in patients with (mild) telomerase deficiencies. Here, the role of
      telomerase in human HSC biology is reviewed, and it is proposed that telomerase
      has an important role in the repair of G-rich DNA.

PMID- 15958714
TI  - Lymphoid potential of primitive bone marrow progenitors evaluated in vitro.
AB  - Bone marrow contains a heterogeneous mixture of mature and maturing precursors of
      blood cells, progenitor cells for myeloid and lymphoid lineages, and
      hematopoietic and mesenchymal stem cells. The differentiation potential of these
      different stem, progenitor, and precursor populations can be evaluated by using
      transplantation and cell culture assays. In this study, we used a stromal cell co
      culture system to evaluate the B and T lineage potential of different subsets of
      mouse bone marrow. We enriched hematopoietic stem (Lin(-)Sca-1(+)c
      kit(+)Thy1.1(low) [Thy1.1(low)]) cells and lymphoid progenitor (Lin(-)Sca-1(+)c
      kit(+)Thy1.1(-) [Thy1.1(-)]) cells from mouse bone marrow and co-cultured these
      populations with OP9 or OP9-DL1 stromal cell lines. Development of the B and T
      lineages was evaluated over time. Both populations gave rise to B and T cells but
      with different kinetics. Thy1.1(-) lymphoid progenitors gave rise to B and T
      lineage cells earlier than did Thy1.1(low) stem cells; and at any given time,
      percentages of differentiating B and T cells were higher in Thy1.1(-) cultures
      than in Thy1.1(low) cultures. We also compared the lineage potential of Thy-1.1(
      ) lymphoid progenitors with that of the recently described common lymphoid
      progenitor 2 (isolated as Lin(-)Sca-1(+)c-kit(-)Thy1.1(-)B220(+) cells
      [B220(+)]). B220(+) cells produced B lineage progeny in OP9 cultures more rapidly
      than did Thy1.1(-) cells and produced higher percentages of differentiating T
      cells in OP9-DL1 cultures. These studies demonstrate the utility of the OP9 and
      OP9-DL1 co-culture systems for evaluation of lymphoid lineage potential and for
      determining the relative position of specific bone marrow populations within the
      hematopoietic hierarchy.

PMID- 15958716
TI  - The stem cell continuum.
AB  - Hematopoietic stem cells have been felt to exist in a hierarchical structure with
      a relatively fixed phenotype at each stage of differentiation. Recent studies on
      the phenotype of the marrow hematopoietic stem cell indicate that it is not a
      fixed entity, but rather that it fluctuates and shows marked heterogeneity. Past
      studies have shown that stem cell engraftment characteristics, adhesion protein,
      and gene expression varies with the phase of the cell cycle. More recently, we
      demonstrated that progenitor numbers and differentiation potential also vary
      reversibly during one cytokine-induced cell cycle transit. We have also shown
      high levels of conversion of marrow cells to skeletal muscle and lung cells,
      indicating a different level of plasticity. Recently, we demonstrated that homing
      to lung and conversion to lung cells in a mouse transplant model also fluctuates
      reversibly with cell cycle transit. This could be considered plasticity squared.
      These data indicate that marrow stem cells are regulated on a continuum related
      to the cell cycle both as to hematopoietic and to nonhematopoietic
      differentiation.

PMID- 15958717
TI  - Human adaptive immune system Rag2-/-gamma(c)-/- mice.
AB  - Although many biologic principles are conserved in mice and humans, species
      specific differences exist, for example, in susceptibility and response to
      pathogens, that often do not allow direct implementation of findings in
      experimental mice to humans. Research in humans, however, for ethical and
      practical reasons, is largely restricted to in vitro assays that lack components
      and the complexity of a living organism. To nevertheless study the human
      hematopoietic and immune system in vivo, xenotransplantation assays have been
      developed that substitute human components to small animals. Here, we summarize
      our recent findings that transplantation of human cord blood CD34(+) cells to
      newborn Rag2(-/-)gamma(c)(-/-) mice leads to de novo development of major
      functional components of the human adaptive immune system. These human adaptive
      immune system Rag2(-/-)gamma(c)(-/-) (huAIS-RG) mice can now be used as a
      technically straightforward preclinical model to evaluate in vivo human adaptive
      immune system development as well as immune responses, for example, to vaccines
      or live infectious pathogens.

PMID- 15958718
TI  - Potentiation of P2X1 ATP-gated currents by 5-hydroxytryptamine 2A receptors
      involves diacylglycerol-dependent kinases and intracellular calcium.
AB  - Postsynaptic P2X1 ATP-gated channels are expressed in smooth muscle cells of the
      vascular and genitourinary systems, where they mediate desensitizing neurogenic
      contractions. Using the model of the isolated rat tail artery, we show that the
      vasoactive mediator 5-hydroxytryptamine (5-HT), via the 5-HT2A metabotropic
      receptor, regulates the desensitization kinetics of P2X1 responses by increasing
      their rate of recovery. Reconstituting the potentiation of P2X1 ATP-gated
      currents by 5-HT2A receptors in the Xenopus oocyte expression system, we provide
      evidence that this modulation depends on the activation of novel protein kinase C
      isoforms and protein kinase D (also named PKCmu) downstream of phospholipase
      Cbeta. Other major kinases like Ca2+/calmodulin kinase II, protein kinase A,
      mitogen-activated protein kinases, and tyrosine kinases were found not to be
      involved. Moreover, we report that buffering intracellular Ca2+ ions with the
      chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)
      decreases the rate of recovery of P2X1 responses and increases their sensitivity
      to potentiation by 5-HT2A receptors or by the diacylglycerol analog phorbol ester
      12-myristate 13-acetate. We conclude that intracellular Ca2+ and a subset of
      diacylglycerol-dependent protein kinases regulate the activity of P2X1 receptor
      channels by modulating their recovery from desensitization.

PMID- 15958719
TI  - Multiple components of 2,4-dichlorophenoxyacetic acid uptake by rat choroid
      plexus.
AB  - Initial rates of uptake of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D;
      20 microM) were measured in intact lateral choroid plexus from rat. Although
      inhibition of uptake by millimolar concentrations of estrone sulfate (ES) and
      unlabeled 2,4-D was maximal at 85%, inhibition by p-aminohippurate (PAH)
      saturated at about 50%. Inhibition by ES plus PAH was no greater than by ES or
      2,4-D alone. Thus, inhibition studies indicated three distinct components of
      uptake; two mediated and one not. The sodium-dependent component of 2,4-D uptake
      coincided with the PAH-sensitive component, indicating uptake mediated by organic
      anion transporter subtype (Oat) 3. Consistent with this, efflux of 2,4-D from
      preloaded tissue was accelerated by all Oat3 substrates tested, and 2,4-D
      increased the efflux of the Oat3 substrate, PAH. Consistent with the inhibition
      data, kinetic analysis showed three components of 2,4-D uptake: a nonmediated
      component (linear kinetics), a high-affinity component, and a low-affinity
      component. The high-affinity component appeared to coincide with the PAH
      sensitive and sodium-dependent component characterized in inhibition studies. The
      PAH-insensitive, low-affinity component was inhibited by ES,
      dehydroepiandrosterone sulfate, and taurocholate but not by 5-hydroxyindole
      acetic acid. Thus, the first step in transport of 2,4-D from cerebrospinal fluid
      to blood involves two transporters: Oat3 and a PAH-insensitive, sodium
      independent transporter. Based on inhibitor profile, the latter may be Oatp3.

PMID- 15958720
TI  - Soy isoflavones improve endothelial function in spontaneously hypertensive rats
      in an estrogen-independent manner: role of nitric-oxide synthase, superoxide, and
      cyclooxygenase metabolites.
AB  - The aim of this study was to analyze the effects of the isoflavones genistein and
      daidzein, and the mammalian estrogen 17beta-estradiol on endothelial function in
      isolated aortic rings from male spontaneously hypertensive rats (SHR) and Wistar
      Kyoto rats (WKY). Relaxation to acetylcholine on precontracted rings was impaired
      and endothelium-dependent contraction to acetylcholine in aortic rings was
      increased in SHR compared with WKY. Aortic NADPH-stimulated O(2)(-) release and
      prostaglandin (PG)H(2) production evoked by acetylcholine were increased, whereas
      nitric-oxide synthase activity was reduced in SHR versus WKY. Genistein,
      daidzein, or 17beta-estradiol enhanced the relaxant response to acetylcholine and
      decreased the endothelium-dependent vasoconstrictor responses to acetylcholine in
      SHR, but not in WKY, and these effects were not modified by the estrogen receptor
      antagonist ICI 182,780 (7alpha,17beta-[9[(4,4,5,5,5-pentafluoropentyl)
      sulfinyl]nonyl]estra-1,3,5(10)-triene-3,17-diol). Moreover, isoflavones enhanced
      nitric-oxide (NO) synthase activity and inhibited NADPH-stimulated O(2)(-)
      roduction and endothelial release of PGH(2). The contractions induced by the TP
      receptor agonist U46619 (9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin
      F(2alpha)) in denuded aortic rings were inhibited by genistein, daidzein, and
      17beta-estradiol in both strains. In conclusion, the isoflavones genistein and
      daidzein and 17beta-estradiol restore endothelial function in male SHR through
      estrogen receptor-independent mechanisms. Increased NO production and protection
      of NO from O(2)(-)-driven inactivation might be involved in the improvement of
      vascular relaxation to acetylcholine in aortic rings from SHR. Moreover,
      isoflavones and 17beta-estradiol inhibited aortic endothelium-dependent
      contraction to acetylcholine in SHR by reducing the endothelial PGH(2) release
      and its vasoconstrictor response.

PMID- 15958721
TI  - Serious allergic reactions following tuberculin skin tests.

PMID- 15958722
TI  - Sleep disturbances and childhood sexual abuse.
AB  - OBJECTIVE: This longitudinal, prospective study examined the relationship between
      childhood sexual abuse and later sleep problems in adolescence while taking into
      account cooccurring psychopathology that is closely related to sleep disruption
      [e.g., depression and posttraumatic stress disorder (PTSD)]. METHOD: Sleep
      disturbances in 147 females (78 sexually abused; 69 comparison) were assessed 10
      years after disclosure of substantiated abuse. The follow-up protocol included
      self-report questions regarding typical sleeping patterns and sleep disturbances
      as well as measures of depression, PTSD, and lifetime victimization histories.
      RESULTS: Sleep disturbances correlated significantly with both depression and
      PTSD. Hierarchical regression analysis showed that sexually abused participants
      reported significantly greater rates of sleep disturbances than comparison
      participants above and beyond depression and PTSD. Sleep disturbances were
      related to revictimization rates independent of sexual abuse, depression, and
      PTSD. CONCLUSIONS: Assessments of sleep disturbances should be integrated into
      standard of care for adolescents who have experienced sexual abuse.

PMID- 15958723
TI  - Effects of fish oil supplementation on kidney transplantation: a systematic
      review and meta-analysis of randomized, controlled trials.
AB  - The objective of this study was to assess the effects of omega-3 fatty acid
      supplementation on various kidney transplant-related outcomes. A systematic
      review and meta-analysis was performed of published randomized, controlled trials
      (RCT). There were 16 kidney transplant RCT with a total of 812 patients. All
      trials evaluated fish oil with dosages that ranged from 1.2 to 5.4 g/d. No
      consistent benefits were observed for any outcome with the exception of a modest
      benefit on triglycerides. A meta-analysis of rejection episodes found no
      significant benefit on either early (<6 mo posttransplantation) or late episodes.
      The overall relative risk of having at least one rejection episode in those who
      received fish oil was 0.91 (95% confidence interval 0.74 to 1.10) in four studies
      with a follow-up of 1 yr. A meta-analysis of eight RCT of graft survival found no
      significant benefit (relative risk 1.00, 95% confidence interval 0.96 to 1.05).
      The available data (mostly derived from older studies with important methodologic
      limitations) do not demonstrate a consistent, clinically important benefit of
      fish oil in kidney transplantation.

PMID- 15958724
TI  - Effect of nitric oxide-cGMP-dependent protein kinase activation on advanced
      glycation end-product-induced proliferation in renal fibroblasts.
AB  - Renal interstitial fibrosis is believed to play a key role in the development of
      diabetic nephropathy (DN), and advanced glycation end-products (AGE) may
      contribute importantly to this. Recent reports have shown that nitric oxide (NO)
      is closely linked to the renal interstitial fibrosis of DN. In this study, the
      mechanisms by which NO and its downstream signals mediate the AGE-induced
      proliferative response in normal rat kidney fibroblasts (NRK-49F) are examined.
      AGE decreased NO production, cyclic guanosine 5'monophosphate (cGMP) synthesis,
      and cGMP-dependent protein kinase (PKG) activation time- and dose-dependently.
      These effects were not observed when cells were treated with nonglycated BSA. NO
      and inducible nitric oxide synthase (iNOS) stimulated by NO donors S-nitroso-N
      acetylpenicillamine (SNAP)/sodium nitroprusside (SNP) and PKG activator 8-para
      chlorophenylthio-cGMP (8-pCPT-cGMP) prevented both AGE-induced proliferation and
      Janus kinase 2 (JAK2)-signal transducers and activators of transcription 5
      (STAT5) activation but not p42/p44 mitogen-activated protein kinase (MAPK)
      activation. The ability of NO-PKG to inhibit AGE-induced cell cycle progression
      was verified by the observation that SNAP, SNP, and 8-pCPT-cGMP inhibited both
      cyclin D1 and cdk4 activation. Furthermore, induction of NO-PKG significantly
      increased p21Waf1/Cip1 expression in AGE-treated NRK-49F cells. The data suggest
      that the NO-PKG pathway inhibits AGE-induced proliferation by suppressing
      activation of JAK2-STAT5 and cyclin D1/cdk4 and induction of p21Waf1/Cip1.

PMID- 15958725
TI  - Aldosterone-induced serum and glucocorticoid-induced kinase 1 expression is
      accompanied by Nedd4-2 phosphorylation and increased Na+ transport in cortical
      collecting duct cells.
AB  - Aldosterone plays a central role in Na+ homeostasis by controlling Na+
      reabsorption in the aldosterone-sensitive distal nephron involving the epithelial
      Na+ channel (ENaC). Part of the effects of aldosterone is mediated by serum and
      glucocorticoid-induced kinase 1 (Sgk1), a Ser/Thr kinase whose expression is
      rapidly induced by aldosterone and that increases in heterologous expression
      systems ENaC cell surface abundance and activity. Previous work in Xenopus laevis
      oocytes suggested that Sgk1 phosphorylates specific residues (Ser212 and Ser328)
      on the ubiquitin-protein ligase Nedd4-2, an enzyme that directly interacts with
      ENaC and negatively controls channel density at the plasma membrane. It further
      indicated that phosphorylation of Nedd4-2 led to impairment of ENaC/Nedd4-2
      interaction and consequently to more channels at the cell surface. These data
      suggested a novel mode of aldosterone-dependent action, yet this was not
      demonstrated formally in epithelial cells that physiologically express ENaC. Here
      it is shown, with the use of an anti-phospho-Ser328-mNedd4-2 antibody, that 2 to
      6 h of aldosterone treatment induces an increase in Nedd4-2 phosphorylation, both
      in a mouse cortical collecting duct cell line (mpkCCDcl4) and in kidneys of
      adrenalectomized rats. This augmentation, which is accompanied by a raise in Sgk1
      expression and transepithelial Na+ transport, is sensitive to
      phosphatidylinositol-3 kinase inhibition, as is Sgk1 phosphorylation and Na+
      transport. Hence, these data provide evidence in cortical collecting duct cells
      in vitro and in vivo that Sgk1-dependent phosphorylation of Nedd4-2 is part of
      the aldosterone response.

PMID- 15958726
TI  - Reduced plasma pyrophosphate levels in hemodialysis patients.
AB  - Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been
      shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was
      demonstrated recently that endogenous production of PPi prevents calcification of
      rat aorta that are cultured in high concentrations of calcium and phosphate. For
      determining whether PPi metabolism is altered in hemodialysis patients, plasma
      levels and dialytic clearance of PPi were measured in stable hemodialysis
      patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically
      stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P
      < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not
      altered in dialysis patients. There was a weak inverse correlation with age in
      normal individuals but not in dialysis patients. Plasma [PPi] in dialysis
      patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+],
      parathyroid hormone, or the dose of dialysis, and levels did not vary between
      interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after
      standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2
      cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was
      43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was
      greater than the plasma pool but less than the estimated extracellular fluid
      pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular
      PPi is removed as well. It is concluded that plasma [PPi] is reduced in
      hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some
      patients were below those that have previously been shown to prevent
      calcification of vessels in culture, suggesting that altered PPi metabolism could
      contribute to vascular calcification in hemodialysis patients.

PMID- 15958727
TI  - Carcinogenic potential of ovulatory genotoxicity.
AB  - Ovulation is a rate-limiting event for the perpetuation of a species;
      unfortunately, it imparts a cancer risk. Reactive oxidants generated during the
      mechanics of ovulatory follicular rupture damage the DNA of ovarian surface
      epithelial cells that are located within a limited diffusion radius. Those cells
      that survive the trauma of ovulation, along the margins of a ruptured follicle,
      proliferate and migrate to reconcile the discontinuity within the ovarian
      epithelium created at the site of oocyte release. It is conceivable that clonal
      expansion of an ovarian surface epithelial cell with unrepaired DNA, but not
      committed to death, could be an initiating factor in the etiology of common
      ovarian cancer. In fact, the majority of cancers of the ovary are derived from
      the surface epithelium; and circumstances that avert ovulation (oral
      contraceptive use, pregnancy/lactation) protect against ovarian adenocarcinoma.
      Not surprisingly, the genotoxic potential of ovulation is exacerbated by
      malfunctions in tumor suppressor/cell-cycle arrest and base-excision repair
      mechanisms. Recent experimental evidence indicates that vitamin E and
      progesterone protect against ovarian metaplasia by negating the oxidative stress
      of ovulation and by enhancing the repair capacity (genomic integrity) of the
      surface epithelium, respectively. Ovarian cancer of surface epithelial origin is
      a deadly insidious disease because it characteristically remains asymptomatic
      until it has metastasized throughout the abdominal cavity; therefore, prevention
      is a high priority.

PMID- 15958728
TI  - The translationally controlled tumor protein is a novel calcium binding protein
      of the human placenta and regulates calcium handling in trophoblast cells.
AB  - The translationally controlled tumor protein (TPT1, also known as TCTP) is a
      highly conserved, abundantly expressed protein found in mammals as well as in a
      wide range of other organisms of both the animal and plant kingdom. Initially
      considered as a growth-related protein, later studies showed TPT1 is endowed with
      multiple biological activities, including calcium binding. The present study
      aimed to evaluate the expression of TPT1 in the human placenta and to examine the
      functional role of the protein in the calcium binding and homeostasis of
      trophoblast cells. Samples were analyzed by Western blot, reverse transcription
      polymerase chain reaction and immunohistochemistry. The effect of TPT1 knockdown
      by small interfering RNA (siRNA) on calcium uptake and buffering was assessed in
      the HTR-8/SVneo cell line. TPT1 protein and mRNA were detected in first-trimester
      and term placenta. In the tissue, TPT1 was localized in the villous trophoblast.
      TPT1 expression significantly increased during gestation, with the higher protein
      and mRNA levels reached at term. Recombinant placental TPT1 bound calcium in
      vitro, while downregulation of the protein levels by siRNA in HTR-8/SVneo cells
      was associated with a reduced cellular calcium-uptake activity and buffering
      capacity. These data demonstrate, for the first time, the expression of TPT1 in
      the human placenta and support a direct role of the protein in placental calcium
      transport.

PMID- 15958729
TI  - Maturation of bovine oocytes in the presence of leptin improves development and
      reduces apoptosis of in vitro-produced blastocysts.
AB  - The series of events associated with oocyte growth and maturation determines the
      oocyte's ability to undergo successful fertilization, cleavage and embryonic
      development. Among the molecules involved in these events, leptin has been
      identified as a modulator of oocyte function. Experiments were conducted to
      determine whether leptin treatment of oocytes during maturation affects their
      developmental capacity after fertilization and whether it has long-lasting
      effects on apoptosis and gene expression in the resulting blastocysts. Cumulus
      oocyte complexes (COCs) were matured in serum-free medium containing 0 (control),
      1, 10, or 100 ng/ml leptin or in medium supplemented with 10% (v/v) estrous cow
      serum (ECS). Addition of leptin during oocyte maturation had no effect on
      cleavage rate after fertilization. However, an increased proportion of oocytes
      that matured in the presence of 1 or 10 ng/ml leptin developed to blastocysts,
      which exhibited increased cell numbers. The proportion of apoptotic cells was
      reduced in blastocysts originating from leptin- or ECS-treated oocytes.
      Transcript levels of the genes encoding leptin receptor (LEPR), signal transducer
      and activator of transcription (STAT3), BCL2 associated X-protein (BAX), and
      baculoviral inhibitor of apoptosis protein repeat-containing 4 (BIRC4, also known
      as XIAP), were determined by reverse transcriptase-quantitative polymerase chain
      reaction analysis of expanded and hatched blastocysts. Depending on the dose
      used, leptin treatment of oocytes resulted in increased LEPR, STAT3, and BIRC4
      mRNA levels and reduced BAX mRNA levels in blastocysts. In conclusion, leptin
      improved the ability of the oocyte to sustain embryonic development and had long
      term effects on blastocyst apoptosis and transcript abundance of LEPR, STAT3, and
      apoptosis-associated genes.

PMID- 15958730
TI  - Tyrosine phosphorylation of caveolin 1 by oxidative stress is reversible and
      dependent on the c-src tyrosine kinase but not mitogen-activated protein kinase
      pathways in placental artery endothelial cells.
AB  - Acute H(2)O(2) exposure to placental artery endothelial cells induced an array of
      tyrosine-phosphorylated proteins, including caveolin 1 (CAV1) rapid and transient
      tyr(14) phosphorylated in a time- and concentration-dependent manner. Basal
      tyr(14) phosphorylated CAV1 was primarily located at the edges of cells and
      associated with actin filaments. Phosphorylated CAV1 was markedly increased and
      diffused with the disorganization of actin filaments at 20 min, disappeared at
      120 min treatment with 0.2 mM H(2)O(2). Treatment with H(2)O(2) also disorganized
      actin filaments and changed cell shape in a time-dependent manner. Pretreatment
      with antioxidants catalase completely, whereas the other tested superoxide
      dismutase, N-acetyl-l-cysteine and sodium formate partially attenuated H(2)O(2)
      induced CAV1 phosphorylation in a concentration-dependent manner. Acute treatment
      with H(2)O(2) activated multiple signaling pathways, including the mitogen
      activated protein kinases (MAPK) members (MAPK3/1-ERK2/1, MAPK8/9-JNK1/2, and
      MAPK11-p38(mapk)) and the c-src tyrosine kinase (CSK). Pharmacological studies
      demonstrated that, among these pathways, only the blockade of CSK activation
      abolished H(2)O(2)-induced CAV1 phosphorylation. Additionally, H(2)O(2)-induced
      CAV1 phosphorylation was reversible rapidly (<10 min) upon H(2)O(2) withdrawal.
      Because maternal and fetal endothelia must make dynamic adaptations to oxidative
      stress resulting from enhanced pregnancy-specific oxygen metabolism favoring
      prooxidant production, which is emerging as one of the leading causes of the
      dysfunctional activated endothelium during pregnancy, these unique features of
      CAV1 phosphorylation on oxidative stress observed implicate an important role of
      CAV1 in placental endothelial cell biology during pregnancy.

PMID- 15958731
TI  - Early placental insulin-like protein (INSL4 or EPIL) in placental and fetal
      membrane growth.
AB  - Early placental insulin-like protein (INSL4 or EPIL) is a member of the insulin
      superfamily of hormones, which is highly expressed in the placenta. We have
      confirmed this at term and shown it to be expressed by the maternal decidua.
      Although an abundance of locally acting growth factors are produced within the
      uterus during pregnancy, we hypothesized that INSL4 plays an important role in
      fetal and placental growth. We have demonstrated with cell lines and primary
      cells that it has a growth-inhibitory effect by causing apoptosis and loss of
      cell viability. We used primary amniotic epithelial cells for flow cytometry to
      show that INSL4 caused apoptosis, which was dose-related and significant (P <
      0.05) at 50 ng/ml. This was confirmed by measurement of the nuclear matrix
      protein in the media. In comparison, relaxin treatment (up to 200 ng/ml) had no
      effect on apoptosis. The addition of INSL4 (3-30 ng/ml) also caused a loss of
      cell viability, although it had no effect on the numbers of cells at different
      phases of the cell cycle. Placental apoptosis is an important process in both
      normal placental development and in fetal growth restriction. Therefore, an in
      vivo clinical correlate was sought in fraternal twins exhibiting discordant
      growth. Expression of the INSL4 gene was doubled in the placenta of the growth
      restricted twin compared to the normally grown sibling, suggesting that it may be
      linked to a higher level of apoptosis and loss of cell viability and, therefore,
      that it may contribute to fetal growth restriction.

PMID- 15958732
TI  - Science education: a neuroscientist's view of translational medicine.

PMID- 15958733
TI  - Laminar and columnar organization of ascending excitatory projections to layer
      2/3 pyramidal neurons in rat barrel cortex.
AB  - Excitatory synaptic projections to layer 2/3 (L2/3) pyramidal neurons in brain
      slices from the rat barrel cortex were measured using quantitative laser-scanning
      photostimulation (LSPS) mapping. In the barrel cortex, cytoarchitectonic
      "barrels" and "septa" in L4 define a stereotypical array of landmarks, allowing
      alignment and averaging of LSPS maps from multiple cells in different slices. We
      distinguished inputs to L2 and L3 neurons above barrels and septa. Average input
      maps revealed that barrel-related ascending projections (L4-->2/3barrel)
      interdigitated with a novel septum-related projection (L5A-->2septum). We also
      explored the functional organization of these projections by comparing the input
      maps of multiple cells in individual slices. L2/3 cells sharing the same barrel
      related column showed strong correlations in their input maps, independent of
      their precise locations within the column; otherwise, correlations fell rapidly
      as a function of intersomatic separation. Our data indicate that barrel-related
      and septum-related columns are associated with distinct functional circuits.
      These projections are likely to mediate parallel processing of somatosensory
      signals within the barrel cortex, with L4-->2/3barrel and L5A-->2septum
      representing the intracortical continuations of, respectively, the subcortical
      lemniscal and paralemniscal systems conveying somatosensory information to the
      barrel cortex.

PMID- 15958734
TI  - Pontine maps linking somatosensory and cerebellar cortices are in register with
      climbing fiber somatotopy.
AB  - The cerebropontocerebellar mossy fiber system is a major CNS sensorimotor
      pathway. We used a double-retrograde axonal tracing technique (red and green
      beads) to chart in rats the pontocerebellar projection to different
      electrophysiologically defined climbing fiber zones in the posterior lobe (face
      receiving A2 zone and forelimb- and hindlimb-receiving parts of the C1 zone in
      the paramedian lobule and copula pyramidis, respectively). Individual cortical
      injection sites were verified as located in a given zone by mapping the pattern
      of cell labeling in the inferior olive, whereas labeled cells in the pontine
      nuclei were mapped using computer-aided three-dimensional reconstruction
      techniques. A number of topographical differences were found for the pontine
      projection to the individual zones. Projections to the A2 zone were bilateral,
      whereas to both parts of the C1 zone, the inputs were mainly contralateral.
      Furthermore, the A2 (face), C1 (forelimb), and C1 (hindlimb) zone projections
      were centered in progressively more caudal parts of the pontine nuclei with
      little or no overlap between them. The areas occupied by cell labeling for each
      zone corresponded closely to territories in the pontine nuclei shown previously
      to receive projections from somatotopically equivalent regions of the
      somatosensory cortex. This precise cerebropontocerebellar topography, defined by
      climbing fiber somatotopy, is a new principle of organization for linking
      somatosensory and cerebellar cortices. The convergence of direct and indirect
      sensory projections is likely to have important implications for cerebellar
      cortical processing.

PMID- 15958735
TI  - Nucleokinesis in tangentially migrating neurons comprises two alternating phases:
      forward migration of the Golgi/centrosome associated with centrosome splitting
      and myosin contraction at the rear.
AB  - During rodent cortex development, cells born in the medial ganglionic eminence
      (MGE) of the basal telencephalon reach the embryonic cortex by tangential
      migration and differentiate as interneurons. Migrating MGE cells exhibit a
      saltatory progression of the nucleus and continuously extend and retract branches
      in their neuritic arbor. We have analyzed the migration cycle of these neurons
      using in vitro models. We show that the nucleokinesis in MGE cells comprises two
      phases. First, cytoplasmic organelles migrate forward, and second, the nucleus
      translocates toward these organelles. During the first phase, a large swelling
      that contains the centrosome and the Golgi apparatus separates from the
      perinuclear compartment and moves rostrally into the leading neurite, up to 30
      mum from the waiting nucleus. This long-distance migration is associated with a
      splitting of the centrioles that line up along a linear Golgi apparatus. It is
      followed by the second, dynamic phase of nuclear translocation toward the
      displaced centrosome and Golgi apparatus. The forward movement of the nucleus is
      blocked by blebbistatin, a specific inhibitor of nonmuscle myosin II. Because
      myosin II accumulates at the rear of migrating MGE cells, actomyosin contraction
      likely plays a prominent role to drive forward translocations of the nucleus
      toward the centrosome. During this phase of nuclear translocation, the leading
      growth cone either stops migrating or divides, showing a tight correlation
      between leading edge movements and nuclear movements.

PMID- 15958736
TI  - Bradykinesia induced by dopamine D2 receptor blockade is associated with reduced
      motor cortex activity in the rat.
AB  - Disruption of motor cortex activity is hypothesized to play a major role in the
      slowed movement (bradykinesia) associated with reduced dopaminergic function. We
      recorded single neurons in the motor cortex of free-moving rats performing a
      forelimb-reaching task. The same neurons were examined before and after induction
      of bradykinesia with the D2 dopamine receptor antagonist haloperidol. Within-cell
      changes in the firing rate and firing pattern of individual cells and the
      correlation between simultaneously recorded cells after injection of haloperidol
      were statistically compared with vehicle-only control experiments. During
      haloperidol-induced bradykinesia (mean movement time increase, +231%), there was
      an average 11% decrease in baseline firing rate. Movement-related peaks in firing
      rate were more dramatically affected, with an overall reduction in peak
      amplitudes of 40%. Bradykinesia was also associated with decreased intensity of
      bursting and amplitude of cross-correlation peaks at rest. The results show for
      the first time that significant reductions can be detected in motor cortex
      activity at rest in animals with impaired ability to generate movements induced
      by reduced dopamine action and confirm that impaired movements are associated
      with reduced cortical activation. Together, these changes in neural activity may
      reduce recruitment and rate modulation of motor units in the spinal cord.

PMID- 15958737
TI  - Conditional rhythmicity of ventral spinal interneurons defined by expression of
      the Hb9 homeodomain protein.
AB  - The properties of mammalian spinal interneurons that underlie rhythmic locomotor
      networks remain poorly described. Using postnatal transgenic mice in which
      expression of green fluorescent protein is driven by the promoter for the
      homeodomain transcription factor Hb9, as well as Hb9-lacZ knock-in mice, we
      describe a novel population of glutamatergic interneurons located adjacent to the
      ventral commissure from cervical to midlumbar spinal cord levels. Hb9+
      interneurons exhibit strong postinhibitory rebound and demonstrate pronounced
      membrane potential oscillations in response to chemical stimuli that induce
      locomotor activity. These data provide a molecular and physiological delineation
      of a small population of ventral spinal interneurons that exhibit homogeneous
      electrophysiological features, the properties of which suggest that they are
      candidate locomotor rhythm-generating interneurons.

PMID- 15958738
TI  - Functional magnetic resonance imaging activity during the gradual acquisition and
      expression of paired-associate memory.
AB  - Recent neurophysiological findings from the monkey hippocampus showed dramatic
      changes in the firing rate of individual hippocampal cells as a function of
      learning new associations. To extend these findings to humans, we used blood
      oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI)
      to examine the patterns of brain activity during learning of an analogous
      associative task. We observed bilateral, monotonic increases in activity during
      learning not only in the hippocampus but also in the parahippocampal and right
      perirhinal cortices. In addition, activity related to simple novelty signals was
      observed throughout the medial temporal lobe (MTL) memory system and in several
      frontal regions. A contrasting pattern was observed in a frontoparietal network
      in which a high level of activity was sustained until the association was well
      learned, at which point the activity decreased to baseline. Thus, we found that
      associative learning in humans is accompanied by striking increases in BOLD fMRI
      activity throughout the MTL as well as in the cingulate cortex and frontal lobe,
      consistent with neurophysiological findings in the monkey hippocampus. The
      finding that both the hippocampus and surrounding MTL cortex exhibited similar
      associative learning and novelty signals argues strongly against the view that
      there is a clear division of labor in the MTL in which the hippocampus is
      essential for forming associations and the cortex is involved in novelty
      detection. A second experiment addressed a striking aspect of the data from the
      first experiment by demonstrating a substantial effect of baseline task
      difficulty on MTL activity capable of rendering mnemonic activity as either
      "positive" or "negative."

PMID- 15958739
TI  - Auditory fear conditioning and long-term potentiation in the lateral amygdala
      require ERK/MAP kinase signaling in the auditory thalamus: a role for presynaptic
      plasticity in the fear system.
AB  - In the present study, we examined the role of the auditory thalamus [medial
      division of the medial geniculate nucleus and the adjacent posterior intralaminar
      nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological
      manipulation of intracellular signaling pathways. In the first experiment, rats
      were given intrathalamic infusions of the MEK (mitogen-activated protein kinase
      kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)
      butadiene (U0126) before fear conditioning. Findings revealed that long-term
      memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1
      3 h) of fear conditioning was intact. In the second experiment, rats received
      immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis
      inhibitor 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), or infusion of
      the protein synthesis inhibitor anisomycin. Posttraining infusion of either U0126
      or DRB significantly impaired long-term retention of fear conditioning, whereas
      infusion of anisomycin had no effect. In the final experiment, rats received
      intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing
      stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA).
      Findings revealed that thalamic infusion of U0126 impaired LTP in the LA.
      Together, these results suggest the possibility that MGm/PIN cells that project
      to the LA contribute to memory formation via ERK (extracellular signal-regulated
      kinase)-mediated transcription, but that they do so by promoting protein
      synthesis-dependent plasticity locally in the LA.

PMID- 15958741
TI  - Synaptic tagging and cross-tagging: the role of protein kinase Mzeta in
      maintaining long-term potentiation but not long-term depression.
AB  - Protein kinase Mzeta (PKMzeta) is a persistently active protein kinase C isoform
      that is synthesized during long-term potentiation (LTP) and is critical for
      maintaining LTP. According to "synaptic tagging," newly synthesized, functionally
      important plasticity-related proteins (PRPs) may prolong potentiation not only at
      strongly tetanized pathways, but also at independent, weakly tetanized pathways
      if synaptic tags are set. We therefore investigated whether PKMzeta is involved
      in tagging and contributes to a sustained potentiation by providing strong and
      weak tetanization to two independent pathways and then disrupting the function of
      the kinase by a selective myristoylated zeta-pseudosubstrate inhibitory peptide.
      We found that persistent PKMzeta activity maintains potentiated responses, not
      only of the strongly tetanized pathway, but also of the weakly tetanized pathway.
      In contrast, an independent, nontetanized pathway was unaffected by the
      inhibitor, indicating that the function of PKMzeta was specific to the tagged
      synapses. To further delineate the specificity of the function of PKMzeta in
      synaptic tagging, we examined synaptic "cross-tagging," in which late LTP in one
      input can transform early into late long-term depression (LTD) in a separate
      input or, alternatively, late LTD in one input can transform early into late LTP
      in a second input, provided that the tags of the weak inputs are set. Although
      the PKMzeta inhibitor reversed late LTP, it did not prevent the persistent
      depression at the weakly stimulated, cross-tagged LTD input. Conversely, although
      the agent did not reverse late LTD, it blocked the persistent potentiation of
      weakly tetanized, cross-tagged synapses. Thus, PKMzeta is the first LTP-specific
      PRP and is critical for the transformation of early into late LTP during both
      synaptic tagging and cross-tagging.

PMID- 15958740
TI  - Endogenous activation of metabotropic glutamate receptors modulates GABAergic
      transmission to gonadotropin-releasing hormone neurons and alters their firing
      rate: a possible local feedback circuit.
AB  - Gonadotropin-releasing hormone (GnRH) neurons are the primary central regulators
      of fertility, receiving input from GABAergic afferents via GABA(A) receptors. We
      tested whether metabotropic glutamate receptors (mGluRs) regulate GABA
      transmission to GnRH neurons and GnRH neuronal firing pattern. Whole-cell
      recordings were performed under conditions isolating ionotropic GABA postsynaptic
      currents (PSCs) in brain slices. The broad-spectrum mGluR agonist 1
      aminocyclopentane-1,3-dicarboxylic acid (ACPD) decreased the frequency of GABA(A)
      mediated spontaneous PSCs in a reversible manner. Amplitude and kinetics were not
      altered, suggesting that afferent GABA neurons are the primary targets. TTX
      eliminated the effects of ACPD in most tested neurons. Group II [2-(2,3
      dicarboxycyclopropyl) glycine] and III (L-AP-4) mGluR agonists mediated this
      response; a group I agonist (3,5-dihydroxyphenylglycine) was not effective. The
      broad-spectrum antagonist alpha-methyl-4-carboxyphenylglycine (MCPG) and/or (RS)
      alpha-cyclopropyl-4-phosphonophenylglycine (CPPG) (group III antagonist) enhanced
      spontaneous PSC frequency, particularly when initial frequency was low,
      suggesting that endogenous activation of mGluRs regulates GABA transmission to
      GnRH neurons. Extracellular recordings were used to evaluate GnRH neuron firing
      rate within the network. ACPD reduced firing rate, and MCPG plus CPPG had an
      opposite effect, indicating that mGluRs help control excitability of the GnRH
      network. GnRH neurons express vesicular glutamate transporters, suggesting they
      may corelease this transmitter. Simulation of firing activity in a GnRH neuron
      decreased PSC frequency in that cell, an effect blocked by antagonism of mGluRs
      but not GnRH receptors. These results demonstrate an inhibition of GABAergic
      inputs to GnRH neurons by mGluRs via a presynaptic mechanism. Through this
      mechanism, local glutamate milieu, possibly contributed by GnRH neurons
      themselves, plays an important role in modulating GnRH release and the central
      regulation of fertility.

PMID- 15958742
TI  - The ErbB4 neuregulin receptor mediates suppression of oligodendrocyte maturation.
AB  - Neuregulin is required for proper oligodendrocyte development, but which
      receptors are involved and whether neuregulin promotes or inhibits maturation
      remain controversial. To assess the roles of the neuregulin receptor ErbB4 in
      oligodendrocyte development, we examined oligodendrocyte initiation and
      maturation in cultures derived from erbB4 knock-out mice and rat spinal cord in
      the presence of neutralizing erbB4 antibodies. No differences in the development
      of O4+ oligodendrocytes were detected in the presence or absence of erbB4
      signaling. All four epidermal growth factor receptor family members were detected
      in the ventral neural tube at approximately the time of initial oligodendrocyte
      development, consistent with redundancy in neuregulin receptor signaling at the
      onset of oligodendrocyte development. In contrast, greater numbers of
      differentiated (monoclonal antibody O1+) oligodendrocytes developed in neural
      tube explants from erbB4(-/-) mice than either erbB4(+/+) or erbB4(+/-)
      littermates as well as in cultures treated with anti-erbB4. These data indicate
      that ErbB4 is not required for oligodendrocyte development and, in fact, inhibits
      oligodendrocyte lineage maturation. Together with previous studies, these data
      suggest a model in which early oligodendrocyte lineage development is regulated
      by promiscuous neuregulin receptor signaling, but subsequent lineage progression
      occurs through a balance of receptor-specific promotion or inhibition of
      maturation.

PMID- 15958743
TI  - R-type calcium channels contribute to afterdepolarization and bursting in
      hippocampal CA1 pyramidal neurons.
AB  - Action potentials in pyramidal neurons are typically followed by an
      afterdepolarization (ADP), which in many cells contributes to intrinsic burst
      firing. Despite the ubiquity of this common excitable property, the responsible
      ion channels have not been identified. Using current-clamp recordings in
      hippocampal slices, we find that the ADP in CA1 pyramidal neurons is mediated by
      an Ni2+-sensitive calcium tail current. Voltage-clamp experiments indicate that
      the Ni2+-sensitive current has a pharmacological and biophysical profile
      consistent with R-type calcium channels. These channels are available at the
      resting potential, are activated by the action potential, and remain open long
      enough to drive the ADP. Because the ADP correlates directly with burst firing in
      CA1 neurons, R-type calcium channels are crucial to this important cellular
      behavior, which is known to encode hippocampal place fields and enhance synaptic
      plasticity.

PMID- 15958744
TI  - Bmi1 loss produces an increase in astroglial cells and a decrease in neural stem
      cell population and proliferation.
AB  - The polycomb transcriptional repressor Bmi1 promotes cell cycle progression,
      controls cell senescence, and is implicated in brain development. Loss of Bmi1
      leads to a decreased brain size and causes progressive ataxia and epilepsy.
      Recently, Bmi1 was shown to control neural stem cell (NSC) renewal. However, the
      effect of Bmi1 loss on neural cell fate in vivo and the question whether the
      action of Bmi1 was intrinsic to the NSCs remained to be investigated. Here, we
      show that Bmi1 is expressed in the germinal zone in vivo and in NSCs as well as
      in progenitors proliferating in vitro, but not in differentiated cells. Loss of
      Bmi1 led to a decrease in proliferation in zones known to contain progenitors:
      the newborn cortex and the newborn and adult subventricular zone. This decrease
      was accentuated in vitro, where we observed a drastic reduction in NSC
      proliferation and renewal because of NSC-intrinsic effects of Bmi1 as shown by
      the means of RNA interference. Bmi1(-/-) mice also presented more astrocytes at
      birth, and a generalized gliosis at postnatal day 30. At both stages,
      colocalization of bromodeoxyuridine and GFAP demonstrated that Bmi1 loss did not
      prevent astrocyte precursor proliferation. Supporting these observations, Bmi1(-/
      ) neurospheres generate preferentially astrocytes probably attributable to a
      different responsiveness to environmental factors. Bmi1 is therefore necessary
      for NSC renewal in a cell-intrinsic mode, whereas the altered cell pattern of the
      Bmi1(-/-) brain shows that in vivo astrocyte precursors can proliferate in the
      absence of Bmi1.

PMID- 15958745
TI  - Early development of functional spatial maps in the zebrafish olfactory bulb.
AB  - In the adult olfactory bulb (OB), particular chemical classes of odorants
      preferentially activate glomeruli within loosely defined regions, resulting in a
      coarse and fractured "chemotopic" map. In zebrafish, amino acids and bile acids
      predominantly stimulate glomeruli in the lateral and medial OB, respectively. We
      studied the development of these spatial response maps in zebrafish. At 3 d
      postfertilization (dpf), the OB contained protoglomerular structures that became
      refined and more numerous during subsequent days. In a transgenic zebrafish line
      expressing the Ca2+ indicator protein inverse pericam, mainly in mitral cells,
      odor responses in the OB were first detected at 2.5-3 dpf. Already at this stage,
      amino acids and bile acids evoked activity predominantly in the lateral and
      medial OB, respectively. Two-photon Ca2+ imaging using a synthetic indicator was
      used to reconstruct activity patterns at higher resolution in three dimensions.
      Responses to amino acids and bile acids were detected predominantly in the
      lateral and medial OB, respectively, with little overlap. Between 2.5 and 6 dpf,
      the number of odor-responsive units increased, but the overall spatial
      organization of activity persisted. Hence, a coarse spatial organization of
      functional activity maps is established very early during OB development when
      glomeruli are not yet differentiated. This spatial organization is maintained
      during development and growth of neuronal circuits and may have important
      functions for odor processing in larvae, for the differentiation of glomeruli,
      and for the refinement of activity maps at later developmental stages.

PMID- 15958746
TI  - Endogenous neurotrophins are required for the induction of GABAergic long-term
      potentiation in the neonatal rat hippocampus.
AB  - In the developing rat hippocampus, GABAergic synapses undergo a Ca2+-dependent
      long-term potentiation (LTP(GABA-A)); this form of synaptic plasticity is induced
      in CA3 pyramidal neurons by delivering repetitive depolarizing pulses (DPs) to
      the recorded neuron, and it is expressed as a long-lasting increase in the
      frequency and amplitude of spontaneous GABA(A) receptor-mediated postsynaptic
      currents. In the present study, we examined the role of endogenous tropomyosin
      related kinase receptor B (TrkB) receptor ligands and associated protein tyrosine
      kinases (PTKs) in the induction of LTP(GABA-A). The application of Lavendustin A,
      a broad spectrum PTK inhibitor, blocked the induction of LTP(GABA-A), whereas
      Lavendustin B, its inactive form, had no effect. Moreover, k-252a and k-252b, two
      alkaloids that inhibit the kinase activity of the Trk receptor family, also
      prevented the induction of LTP(GABA-A). On hippocampal slices incubated with the
      soluble form of TrkB receptor IgG (TrkB-IgG), which prevents the activation of
      TrkB receptors by endogenous ligands, DPs failed to induce LTP(GABA-A), whereas
      the incubation with TrkA-IgG or TrkC-IgG had no such effect. Altogether, these
      data indicate that endogenous TrkB ligands and associated PTK activity are
      necessary for the induction of GABAergic LTP in the developing rat hippocampus.

PMID- 15958747
TI  - HCN subunit-specific and cAMP-modulated effects of anesthetics on neuronal
      pacemaker currents.
AB  - General anesthetics have been a mainstay of surgical practice for more than 150
      years, but the mechanisms by which they mediate their important clinical actions
      remain unclear. Ion channels represent important anesthetic targets, and,
      although GABA(A) receptors have emerged as major contributors to sedative,
      immobilizing, and hypnotic effects of intravenous anesthetics, a role for those
      receptors is less certain in the case of inhalational anesthetics. The neuronal
      hyperpolarization-activated pacemaker current (Ih) is essential for oscillatory
      and integrative properties in numerous cell types. Here, we show that clinically
      relevant concentrations of inhalational anesthetics modulate neuronal Ih and the
      corresponding HCN channels in a subunit-specific and cAMP-dependent manner.
      Anesthetic inhibition of Ih involves a hyperpolarizing shift in voltage
      dependence of activation and a decrease in maximal current amplitude; these
      effects can be ascribed to HCN1 and HCN2 subunits, respectively, and both actions
      are recapitulated in heteromeric HCN1-HCN2 channels. Mutagenesis and simulations
      suggest that apparently distinct actions of anesthetics on V(1/2) and amplitude
      represent different manifestations of a single underlying mechanism (i.e.,
      stabilization of channel closed state), with the predominant action determined by
      basal inhibition imposed by individual subunit C-terminal domains and relieved by
      cAMP. These data reveal a molecular basis for multiple actions of anesthetics on
      neuronal HCN channels, highlight the importance of proximal C terminus in
      modulation of HCN channel gating by diverse agents, and advance neuronal
      pacemaker channels as potentially relevant targets for clinical actions of
      inhaled anesthetics.

PMID- 15958748
TI  - Dopamine specifically inhibits forebrain neural stem cell proliferation,
      suggesting a novel effect of antipsychotic drugs.
AB  - Neurogenesis has been implicated in antidepressant drug action and animal models
      of depression, suggesting that proliferating cells play a role in psychiatric
      disorders. Similar studies using antipsychotic drugs have yielded conflicting
      results, perhaps because of the lack of focus on specific cell types. We examine
      the effect of haloperidol on neural stem cells (NSCs), the ultimate precursors
      for adult cell genesis. We show that haloperidol increases NSC numbers, resulting
      in more progenitors and more new neurons and glia in the adult rat brain. The
      increase in NSCs by haloperidol is dependent on central dopamine D2 receptors,
      and these receptors are expressed by NSCs. D2 receptor stimulation in vitro
      inhibits NSC proliferation, which is reversed by haloperidol. Thus, haloperidol
      increases adult mammalian brain proliferation by antagonizing dopamine at D2
      receptors on NSCs. These findings demonstrate a direct link between neural
      activity and NSC proliferation and implicate cell genesis in antipsychotic drug
      effects.

PMID- 15958749
TI  - Visualization of prion infection in transgenic mice expressing green fluorescent
      protein-tagged prion protein.
AB  - Tg(PrP-EGFP) mice express an enhanced green fluorescent protein (EGFP)-tagged
      version of the prion protein (PrP) that behaves like endogenous PrP in terms of
      its posttranslational processing, anatomical localization, and functional
      activity. In this study, we describe experiments in which Tg(PrP-EGFP) mice were
      inoculated intracerebrally with scrapie prions. Although PrP-EGFP was incapable
      of sustaining prion infection in Tg(PrP-EGFP)/Prn-p(0/0) mice, it acted as a
      dominant-negative inhibitor that bound to, and fluorescently marked, deposits of
      PrPSc generated from endogenous PrP in Tg(PrP-EGFP)/Prn-p(+/+) mice. Scrapie
      infection of these latter animals caused a progressive accumulation of
      fluorescent PrP-EGFP aggregates in neuropil, axons, and prominently in the Golgi
      apparatus of neurons. Our results provide an entirely new picture of PrPSc
      localization during the course of prion infection, and they identify for the
      first time intracellular sites of PrPSc formation that are not well visualized
      with conventional immunohistochemical techniques.

PMID- 15958750
TI  - Local protein synthesis mediates a rapid increase in dendritic elongation factor
      1A after induction of late long-term potentiation.
AB  - The maintenance of long-term potentiation (LTP) requires a brief period of
      accelerated protein synthesis soon after synaptic stimulation, suggesting that an
      early phase of enhanced translation contributes to stable LTP. The mechanism
      regulating protein synthesis and the location and identities of mRNAs translated
      are not well understood. Here, we show in acute brain slices that the induction
      of protein synthesis-dependent hippocampal LTP increases the expression of
      elongation factor 1A (eEF1A), the mRNA of which contains a 5' terminal
      oligopyrimidine tract. This effect is blocked by rapamycin, indicating that the
      increase in EF1A expression is mediated by the mammalian target of rapamycin
      (mTOR) pathway. We find that mRNA for eEF1A is present in pyramidal cell
      dendrites and that the LTP-associated increase in eEF1A expression was intact in
      dendrites that had been severed from their cell bodies before stimulation. eEF1A
      levels increased within 5 min after stimulation in a translation-dependent
      manner, and this effect remained stable for 3 h. These results suggest a
      mechanism whereby synaptic stimulation, by signaling through the mTOR pathway,
      produces an increase in dendritic translational capacity that contributes to LTP
      maintenance.

PMID- 15958756
TI  - Anti-tumour necrosis factor alpha therapy: can we afford it?

PMID- 15958757
TI  - Association between radiographic damage of the spine and spinal mobility for
      individual patients with ankylosing spondylitis: can assessment of spinal
      mobility be a proxy for radiographic evaluation?
AB  - OBJECTIVE: To demonstrate the association between various measures of spinal
      mobility and radiographic damage of the spine in individual patients with
      ankylosing spondylitis, and to determine whether the assessment of spinal
      mobility can be a proxy for the assessment of radiographic damage. METHODS:
      Radiographic damage was assessed by the mSASSS. Cumulative probability plots
      combined the radiographic damage score of an individual patient with the
      corresponding score for nine spinal mobility measures. Receiver operating
      characteristic analysis was performed to determine the cut off level of every
      spinal mobility measure that discriminates best between the presence and absence
      of radiographic damage. Three arbitrary cut off levels for radiographic damage
      were investigated. Likelihood ratios were calculated to explore further the
      diagnostic properties of the spinal mobility measures. RESULTS: Cumulative
      probability plots showed an association between spinal mobility measures and
      radiographic damage for the individual patient. Irrespective of the chosen cut
      off level for radiographic progression, lateral spinal flexion and BASMI
      discriminated best between patients with and those without structural damage.
      Even the best discriminatory spinal mobility assessments misclassified a
      considerable proportion of patients (up to 20%). Intermalleolar distance
      performed worst (up to 30% misclassifications). Lateral spinal flexion best
      predicted the absence of radiographic damage, and a modified Schober test best
      predicted the presence of radiographic damage. CONCLUSION: This study
      unequivocally demonstrated a relationship between spinal mobility and
      radiographic damage. However, spinal mobility cannot be used as a proxy for
      radiographic evaluation in an individual patient.

PMID- 15958758
TI  - Infliximab treatment reduces complement activation in patients with rheumatoid
      arthritis.
AB  - BACKGROUND: Tumour necrosis factor (TNF) blocking agents decrease C reactive
      protein (CRP) levels in rheumatoid arthritis (RA). It has been shown that CRP may
      contribute to complement activation in RA. OBJECTIVE: To assess the effect of
      intravenous infliximab treatment on complement activation, especially that
      mediated by CRP, in RA. METHODS: 35 patients with active RA (28 joint count
      Disease Activity Score (DAS28) >4.4) were treated with intravenous injections of
      infliximab (3 mg/kg, at weeks 0, 2, 6, 14, and 22). Clinical response and plasma
      levels of complement activation products, of CRP and of CRP-complement complexes,
      which are specific markers for CRP mediated complement activation, were assessed
      at the indicated time points up to 22 weeks. The relationship between CRP and CRP
      complement complexes was analysed by paired t test between two time points and by
      generalised estimated equation, to test differences of variables over time.
      RESULTS: At 2 weeks after the first dose, infliximab significantly reduced
      overall C3 and C4 activation and plasma levels of CRP and CRP-complement
      complexes were also significantly reduced at this time point. The effects of
      infliximab on CRP and complement continued throughout the observation period and
      were more pronounced in patients with a good response to infliximab treatment.
      CONCLUSION: Treatment with infliximab decreases plasma levels of CRP and CRP
      dependent complement activation products and concomitantly may reduce complement
      activation in RA. Complement activation may be among the effector mechanisms of
      TNF in RA.

PMID- 15958759
TI  - Severe disease in patients with rheumatoid arthritis carrying a mutation in the
      Mediterranean fever gene.
AB  - BACKGROUND: Pyrin is a newly recognised intracellular regulator of inflammation,
      and mutations in MEFV, the gene encoding pyrin, are the cause of familial
      Mediterranean fever. OBJECTIVE: To determine if known mutations of MEFV are
      associated with rheumatoid arthritis (RA) morbidity or can modify RA severity.
      METHODS: The frequency of the three most common MEFV mutations: M694V, V726A, and
      E148Q, was determined in 98 Israeli patients with RA (74 women, 24 men) and
      compared with that in 100 healthy subjects matched for origin. RA severity was
      determined using a new clinical score of 126 grades. The median severity score of
      mutation carrier and non-carrier groups was compared after confounding measures
      were eliminated by logistic regression. RESULTS: 17/98 (17%) patients with RA
      (all women) were heterozygous for common MEFV mutations, predominantly E148Q (12
      patients), and one patient was homozygous for the V726A mutation. The overall
      mutation rate was comparable between patients with RA and healthy subjects.
      Patients carrying a mutation had a higher median severity score than the non
      carrier group (42 v 29, p = 0.0005). The logistic regression model assigned a 15
      fold odds ratio for severe RA in carriers, after adjusting for sex, presence of
      rheumatoid factor, age at onset, and disease duration (n = 97, p = 0.01, 95% CI
      1.74 to 128). CONCLUSION: MEFV, and particularly the E148Q mutation, is an
      independent modifier of the clinical manifestations of RA. This is the second Th1
      type autoimmune disease in which MEFV mutations have been shown to aggravate the
      clinical status.

PMID- 15958761
TI  - Hip joint disease in psoriatic arthritis: risk factors and natural history.
AB  - OBJECTIVE: To determine the natural history of hip joint disease in psoriatic
      arthritis (PsA) and identify clinical risk factors for its early identification.
      PATIENTS AND METHODS: 504 patients with PsA according to ESSG criteria were
      studied. Mean follow up was 5.7 years (range <1-45). Mean age at onset of
      psoriasis was 32 years and of PsA, 39 years. The most common pattern of PsA at
      onset was oligoarticular (49%) and at the latest examination, polyarticular
      (65%). Sacroiliitis or spondylitis was diagnosed in 94 (18.7%) patients. RESULTS:
      32 (6.3%) patients developed psoriatic hip arthropathy, and of these, 26 (81%)
      also had sacroiliitis or spondylitis. In 7/17 (41%) patients the hip became
      affected within 1 year after the onset of PsA. Hip disease occurred more often in
      younger patients. Sex, pattern of peripheral arthritis, duration of psoriasis
      before arthritis affected the distal interphalangeal joints, dactylitis, or
      enthesitis were not associated with the risk of hip disease. Seventeen patients
      were followed up and nine required hip arthroplasty. Sixteen (50%) first had
      arthroplasty within 5 years after the onset of hip pain. CONCLUSIONS: Psoriatic
      hip arthropathy occurs infrequently in PsA and is associated with earlier onset
      of arthritis and psoriatic spondylitis. Bilateral hip involvement and rapid
      progression to hip arthroplasty are common.

PMID- 15958760
TI  - Development of additional autoimmune diseases in a population of patients with
      primary Sjogren's syndrome.
AB  - BACKGROUND: To investigate whether patients with primary Sjogren's syndrome (pSS)
      have an increased tendency to develop other autoimmune diseases. METHODS: A
      retrospective case note review was carried out on 114 patients in whom a
      diagnosis of pSS had been made in a department of rheumatology from 1979 onwards.
      The year of diagnosis of pSS was recorded, plus the diagnosis and year of
      diagnosis of any other identified autoimmune disease. RESULTS: Of the 114
      patients with pSS, seven (6%) were male and 107 (94%) female. Mean age at
      diagnosis of pSS was 53 years (range 21 to 83). Patients were followed up for an
      average of 10.5 years (range 0 to 23). Thirty eight patients (33.3%) were
      diagnosed as having another autoimmune disease, while nine (7.9%) had two or
      more. Thirteen additional autoimmune diseases were identified. Twenty five
      diagnoses (51.0%) were made before the diagnosis of pSS, three (6.1%) within the
      same year, and 21 (42.9%) after the diagnosis. Hypothyroidism was the most common
      autoimmune disease (n = 16). CONCLUSIONS: Although pSS is a relatively benign
      condition, affected individuals have an increased tendency to develop additional
      autoimmune diseases. Patients with pSS should be monitored on a regular basis for
      such diseases.

PMID- 15958762
TI  - Emotion regulation predicts change of perceived health in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To examine whether emotion regulation predicts change of perceived
      health in patients with rheumatoid arthritis (RA). METHODS: Sixty six patients
      (44 female, 22 male; mean (SD) age 57.7 (11.6) years) participated in a
      prospective study. Hierarchical regression analysis was used to predict change of
      perceived health between study entry and follow up (1(1/2) years later) from the
      emotion regulation styles ambiguity, control, orientation, and expression at
      study entry. RESULTS: Valuing and intensely experiencing emotions (emotional
      orientation) predicted a decrease of positive affect. Difficulty recognising and
      expressing emotions (ambiguity) predicted an increase of perceived disease
      activity. Emotion regulation showed no associations with change of negative
      affect and social and physical functioning. CONCLUSIONS: Two styles of emotion
      regulation were shown to have a significant though modest role in the prediction
      of perceived health change in patients with RA. This suggests that the monitoring
      of emotion regulation may help to identify patients who are at risk for a
      reduction of perceived health. If our findings were confirmed by experimental
      research, improving emotion regulation skills might favourably affect perceived
      health.

PMID- 15958763
TI  - Phosphatase-1 and -2A inhibition modulates apoptosis in human osteoarthritis
      chondrocytes independently of nitric oxide production.
AB  - OBJECTIVE: To characterise the role of phosphatase-1 and -2A (PP1/2A) in the
      modulation of apoptosis in human osteoarthritis (OA) chondrocytes. METHODS: Human
      OA chondrocytes were isolated from cartilage obtained from the femoral heads of
      patients undergoing joint replacement surgery. Cell viability was evaluated by
      MTT assay. Apoptosis was quantified by ELISA, which measures DNA fragmentation.
      Nitric oxide (NO) production was evaluated by the Greiss method, and inducible
      nitric oxide synthase (iNOS) protein synthesis was studied by western blotting.
      RESULTS: Inhibition of PP1/2A by the specific inhibitor okadaic acid (OKA) dose
      and time dependently caused a reduction of cell viability (OKA at 50 nmol/l: a
      reduction to 60% and 43% at 48 and 72 hours, respectively). Genomic DNA from
      chondrocytes treated with OKA at 50 and 100 nmol/l for 48 hours displayed
      increased internucleosomal DNA fragmentation by 11 and 13 fields, respectively.
      Light microscopy and DAPI studies showed that OKA induced DNA condensation and
      fragmentation, typical of death by apoptosis. The caspase inhibitors Z-VAD-FMK
      and Z-DEVD-FMK increased cell viability, reduced by OKA at 50 nmol/l to 87% and
      73%, respectively. OKA did not increase iNOS protein synthesis or NO production.
      CONCLUSION: PP1/2A modulate apoptosis in human OA chondrocytes; this is
      independent of NO production but dependent on caspases.

PMID- 15958764
TI  - Achilles tendinosis is associated with sprouting of substance P positive nerve
      fibres.
AB  - OBJECTIVES: To identify and characterise nerve fibres and inflammatory
      alterations in painful Achilles tendinosis and thus gain evidence about the
      origin of pain in Achilles tendinosis. METHODS: The composition of 10 tendon
      samples from patients with a prior history of painful Achilles tendinosis and 10
      samples from patients with spontaneously ruptured tendons but no previous pain
      was compared by immunohistochemistry and conventional histology. RESULTS: The
      presence of granulation tissue was shown in 8/10 cases of Achilles tendinosis.
      Nociceptive substance P (SP) positive nerve fibres were significantly increased,
      and an inflammatory infiltration comprising B and T lymphocytes was found.
      Additionally, small foci with iron positive haemosiderophages, indicating prior
      microtraumatic events, were found in 6/10 samples. None of the spontaneously
      ruptured tendons contained granulation tissue or haemosiderophages. Inflammatory
      infiltration in these patients consisted almost exclusively of granulocytes and
      SP positive nerve fibres were decreased. The density of sympathetic nerve fibres
      did not differ in the two conditions. CONCLUSION: Achilles tendinosis is
      associated with the presence of granulation tissue, haemosiderophages, and SP
      positive nerve fibres, which may transmit the clinically pertinent pain. Achilles
      tendinosis may be caused by repeated microtraumata with ensuing organisation that
      is accompanied by sprouting of nociceptive SP positive nerve fibres.

PMID- 15958765
TI  - Successful treatment of refractory anterior scleritis in primary Sjogren's
      syndrome with rituximab.

PMID- 15958766
TI  - Granulomatous synovialitis with erosions in the shoulder joint: a rare case of
      polyarthritis caused by Mycobacterium kansasii.

PMID- 15958767
TI  - Etanercept in treatment of Felty's syndrome.

PMID- 15958768
TI  - Positron emission tomography use in the diagnosis and follow up of Takayasu's
      arteritis.

PMID- 15958769
TI  - Interleukin (IL) 1alpha, IL1beta, IL receptor antagonist, and IL10 polymorphisms
      in psoriatic arthritis.

PMID- 15958770
TI  - Production of anti-CCP antibodies and matrix metalloproteinase-3 by human
      rheumatoid arthritis synovial tissues using SCID mice.

PMID- 15958771
TI  - Absence of anti-cyclic citrullinated peptide antibodies in erosive
      osteoarthritis: further serological evidence of the disease as a subset of
      osteoarthritis.

PMID- 15958772
TI  - Paternal and maternal exposure to leflunomide: pregnancy and neonatal outcome.

PMID- 15958773
TI  - Spontaneous remission of marginal zone B cell lymphoma in a patient with
      seropositive rheumatoid arthritis after discontinuation of infliximab
      methotrexate treatment.

PMID- 15958774
TI  - Anti-CD20 monoclonal antibody (rituximab) as an adjunct in the treatment of giant
      cell arteritis.

PMID- 15958775
TI  - Systemic sclerosis in Europe: first report from the EULAR Scleroderma Trials And
      Research (EUSTAR) group database.

PMID- 15958776
TI  - Anti-C1q antibodies in renal and non-renal SLE.

PMID- 15958777
TI  - A cellular correlate of learning-induced metaplasticity in the hippocampus.
AB  - Metaplasticity, the plasticity of synaptic plasticity, is thought to have a
      pivotal role in activity-dependent modulation of synaptic connectivity, which
      underlies learning and memory. Metaplasticity is usually attributed to
      modifications in glutamate receptor-mediated synaptic transmission. However,
      experimental evidence and theoretical considerations suggest that learning
      reduces the predisposition for further synaptic strengthening, while behavioral
      studies show that learning capability is enhanced by prior learning. Here we show
      that enhanced neuronal excitability in CA1 pyramidal neurons, but not enhanced
      synaptic transmission, occurs prior to rule learning of an olfactory
      discrimination task. This transient enhancement lasts for 1 day after rule
      learning, is apparent throughout the cell population and results from reduction
      in the medium and slow after-hyperpolarizations that control spike frequency
      adaptation. Such olfactory learning-induced increased excitability in hippocampal
      neurons enhances the rats' learning capability in another hippocampus-dependent
      task, the Morris water maze. Once olfactory discrimination rule learning is
      acquired, its maintenance is not dependent on the reduced post-burst AHP in
      hippocampal neurons. However, the enhanced spatial learning capability of
      olfactory-trained rats in the water maze is diminished once the post burst AHP in
      CA1 pyramidal cells resumes its initial value. We suggest that enhanced
      excitability of CA1 neurons may serve as a mechanism for generalized enhancement
      of hippocampus-dependent learning capability. In the presence of such enhanced
      neuronal excitability, the hippocampal network enters into a 'learning mode' in
      which a variety of hippocampus-dependent skills are acquired rapidly and
      efficiently.

PMID- 15958778
TI  - Distribution of activity across the monkey cerebral cortical surface, thalamus
      and midbrain during rapid, visually guided saccades.
AB  - To examine the distribution of visual and oculomotor activity across the macaque
      brain, we performed functional magnetic resonance imaging (fMRI) on awake,
      behaving monkeys trained to perform visually guided saccades. Two subjects
      alternated between periods of making saccades and central fixations while blood
      oxygen level dependent (BOLD) images were collected [3 T, (1.5 mm)3 spatial
      resolution]. BOLD activations from each of four cerebral hemispheres were
      projected onto the subjects' cortical surfaces and aligned to a surface-based
      atlas for comparison across hemispheres and subjects. This surface-based analysis
      revealed patterns of visuo-oculomotor activity across much of the cerebral
      cortex, including activations in the posterior parietal cortex, superior temporal
      cortex and frontal lobe. For each cortical domain, we show the anatomical
      position and extent of visuo-oculomotor activity, including evidence that the
      dorsolateral frontal activation, which includes the frontal eye field (on the
      anterior bank of the arcuate sulcus), extends anteriorly into posterior principal
      sulcus (area 46) and posteriorly into part of dorsal premotor cortex (area 6).
      Our results also suggest that subcortical BOLD activity in the pulvinar thalamus
      may be lateralized during voluntary eye movements. These findings provide new
      neuroanatomical information as to the complex neural substrates that underlie
      even simple goal-directed behaviors.

PMID- 15958779
TI  - Dorsolateral prefrontal cortex prevents short-latency saccade and vergence: a TMS
      study.
AB  - This study explores whether vergence eye movements along the median plane can be
      triggered with short latencies, and the role of the dorsolateral prefrontal
      cortex (DLPFC) in controlling such movements. We used a gap paradigm and applied
      transcranial magnetic stimulation (TMS) in 10 humans making saccades or vergence.
      TMS over the motor cortex had no effect on any eye movement parameter. TMS over
      DLPFC influenced eye movement initiation but not their metrics. TMS over the
      right DLPFC accelerated the triggering of saccades bilaterally but did not
      influence divergence. TMS over the left DLPFC speeded up the triggering of
      ipsilateral saccades and exacerbated the anticipatory mode of triggering of
      divergence. For convergence, TMS effects were mild: rightward TMS increased the
      proportion of short latencies but failed to shorten the group mean latency;
      leftward TMS influenced triggering in some individuals only. For saccades and
      convergence under TMS, some subjects showed an emerging population of short
      latencies in their latency distribution. Horizontal saccadic intrusions (80% of
      trials) and vertical saccades (recorded in one subject) intruding on vergence
      were unlikely to assist vergence triggering. We conclude that the prefrontal
      mechanisms underlying voluntary eye movement control are similar for saccades and
      vergence although some specificities exist.

PMID- 15958780
TI  - Independence of visual awareness from the scope of attention: an
      electrophysiological study.
AB  - Recent brain imaging studies have revealed that increased neural activity along
      the ventral visual stream and parietal and frontal areas is associated with
      visual awareness. In order to study the time-course and temporal aspects of
      awareness, we examined electrophysiological correlates of conscious vision in two
      masking experiments. The differences in event-related potentials (ERPs) between
      unmasked (consciously recognized) and masked (unrecognized) stimuli were
      considered to be electrophysiological correlates of awareness. Two attentional
      conditions (global, local) were included to examine the relationship between the
      scope of attention and awareness. Two ERP-deflections were found to correlate
      with awareness. First, awareness was associated with a posterior negative
      amplitude shift 130-320 ms after the stimulus. This effect was present in both
      attention conditions, suggesting that it emerges independent of the scope of
      attention. Second, ERPs to unmasked stimuli became more positive as compared with
      masked stimuli around 400 ms, peaking at parietal sites. This effect was
      attenuated in the local attention condition, although the participants were aware
      of the stimuli, suggesting that the late positivity does not directly correlate
      with visual awareness. The results imply that the earlier negativity is the
      earliest and most direct correlate of visual awareness.

PMID- 15958781
TI  - Cell proliferation in the adult hippocampal formation of rodents and its
      modulation by entorhinal and fimbria-fornix afferents.
AB  - New granule neurons are produced in the dentate gyrus (DG) of rodents throughout
      adult life. Recent studies have also reported adult neurogenesis in the cerebral
      cortex in normal animals or after brain injury. However, few of these studies
      focused on the hippocampal formation (HF), a cortical area involved in learning
      and memory in which extensive cell death occurs in neurodegenerative diseases.
      Thus, we studied cell proliferation in the HF of rodents and the intrinsic
      putative neurogenic potential of entorhinal cortex (EC) progenitors. We show that
      only the DG generates new neurons in the HF. In addition, neurospheres from the
      EC differentiate into neurons and glia in vitro and after transplantation in the
      adult DG. We also analyzed whether the absence of the synaptic input from the
      main hippocampal afferents induces neuronal generation in the HF outside the DG
      and/or regulates the proliferation of DG neuroprogenitors. We show that the
      denervation of the hippocampus does not induce neurogenesis in HF regions other
      than the DG. However, neuroprogenitor proliferation in the DG is reduced after
      fimbria-fornix lesions but not after entorhinal deafferentation, which supports
      the view that neuroprogenitor proliferation and/or differentiation in the DG are
      controlled from basal forebrain/septal neurons.

PMID- 15958782
TI  - Extensive human DNA contamination in extracts from ancient dog bones and teeth.
AB  - Ancient DNA (aDNA) sequences, especially those of human origin, are notoriously
      difficult to analyze due to molecular damage and exogenous DNA contamination.
      Relatively few systematic studies have focused on this problem. Here we
      investigate the extent and origin of human DNA contamination in the most
      frequently used sources for aDNA studies, that is, bones and teeth from museum
      collections. To distinguish contaminant DNA from authentic DNA we extracted DNA
      from dog (Canis familiaris) specimens. We monitored the presence of a 148-bp
      human-specific and a 152-bp dog-specific mitochondrial DNA (mtDNA) fragment in
      DNA extracts as well as in negative controls. The total number of human and dog
      template molecules were quantified using real-time polymerase chain reaction
      (PCR), and the sequences were characterized by amplicon cloning and sequencing.
      Although standard precautions to avoid contamination were taken, we found that
      all samples from the 29 dog specimens contained human DNA, often at levels
      exceeding the amount of authentic ancient dog DNA. The level of contaminating
      human DNA was also significantly higher in the dog extracts than in the negative
      controls, and an experimental setup indicated that this was not caused by the
      carrier effect. This suggests that the contaminating human DNA mainly originated
      from the dog bones rather than from laboratory procedures. When cloned, fragments
      within a contaminated PCR product generally displayed several different
      sequences, although one haplotype was often found in majority. This leads us to
      believe that recognized criteria for authenticating aDNA cannot separate
      contamination from ancient human DNA the way they are presently used.

PMID- 15958783
TI  - Evolutionary implications of bacterial polyketide synthases.
AB  - Polyketide synthases (PKS) perform a stepwise biosynthesis of diverse carbon
      skeletons from simple activated carboxylic acid units. The products of the
      complex pathways possess a wide range of pharmaceutical properties, including
      antibiotic, antitumor, antifungal, and immunosuppressive activities. We have
      performed a comprehensive phylogenetic analysis of multimodular and iterative PKS
      of bacteria and fungi and of the distinct types of fatty acid synthases (FAS)
      from different groups of organisms based on the highly conserved ketoacyl
      synthase (KS) domains. Apart from enzymes that meet the classification standards
      we have included enzymes involved in the biosynthesis of mycolic acids,
      polyunsaturated fatty acids (PUFA), and glycolipids in bacteria. This study has
      revealed that PKS and FAS have passed through a long joint evolution process, in
      which modular PKS have a central position. They appear to have derived from
      bacterial FAS and primary iterative PKS and, in addition, share a common ancestor
      with animal FAS and secondary iterative PKS. Furthermore, we have carried out a
      phylogenomic analysis of all modular PKS that are encoded by the complete
      eubacterial genomes currently available in the database. The phylogenetic
      distribution of acyltransferase and KS domain sequences revealed that multiple
      gene duplications, gene losses, as well as horizontal gene transfer (HGT) have
      contributed to the evolution of PKS I in bacteria. The impact of these factors
      seems to vary considerably between the bacterial groups. Whereas in
      actinobacteria and cyanobacteria the majority of PKS I genes may have evolved
      from a common ancestor, several lines of evidence indicate that HGT has strongly
      contributed to the evolution of PKS I in proteobacteria. Discovery of new
      evolutionary links between PKS and FAS and between the different PKS pathways in
      bacteria may help us in understanding the selective advantage that has led to the
      evolution of multiple secondary metabolite biosyntheses within individual
      bacteria.

PMID- 15958784
TI  - A dissection of volatility in yeast.
AB  - It has been suggested that volatility, the proportion of mutations which change
      an amino acid, can be used to infer the level of natural selection acting upon a
      gene. This conjecture is supported by a correlation between volatility and the
      rate of nonsynonymous substitution (dN), or the ratio of nonsynonymous and
      synonymous substitution rates, in a variety of organisms. These organisms include
      yeast, in which the correlations are quite strong. Here we show that these
      correlations are a by-product of a correlation between synonymous codon bias
      toward translationally optimal codons and dN. Although this analysis suggests
      that volatility is not a good measure of the selection, we suggest that it might
      be possible to infer something about the level of natural selection, from a
      single genome sequence, using translational codon bias.

PMID- 15958785
TI  - A national program for injury prevention in children and adolescents: the injury
      free coalition for kids.
AB  - Injury is the leading cause of death and a major source of preventable disability
      in children. Mechanisms of injury are rooted in a complex web of social,
      economic, environmental, criminal, and behavioral factors that necessitate a
      multifaceted, systematic injury prevention approach. This article describes the
      injury burden and the way physicians, community coalitions, and a private
      foundation teamed to impact the problem first in an urban minority community and
      then through a national program. Through our injury prevention work in a resource
      limited neighborhood, a national model evolved that provides a systematic
      framework through which education and other interventions are implemented.
      Interventions are aimed at changing the community and home environments
      physically (safe play areas and elimination of community and home hazards) and
      socially (education and supervised extracurricular activities with mentors). This
      program, based on physician-community partnerships and private foundation
      financial support, expanded to 40 sites in 37 cities, representing all 10 US
      trauma regions. Each site is a local adaptation of the Injury Free Coalition
      model also referred to as the ABC's of injury prevention: A, "analyze injury data
      through local injury surveillance"; B, "build a local coalition"; C, "communicate
      the problem and raise awareness that injuries are a preventable public health
      problem"; D, "develop interventions and injury prevention activities to create
      safer environments and activities for children"; and E, "evaluate the
      interventions with ongoing surveillance." It is feasible to develop a
      comprehensive injury prevention program of national scope using a voluntary
      coalition of trauma centers, private foundation financial and technical support,
      and a local injury prevention model with a well-established record of reducing
      and sustaining lower injury rates for inner-city children and adolescents.

PMID- 15958786
TI  - Urban youth violence: do definitions and reasons for violence vary by gender?
AB  - This study explored how young boys and girls living in low income urban
      neighborhoods defined and described reasons associated with youth violence. Five
      focus groups were conducted with 29 youth between the ages of 8 and 12 recruited
      from four selected study neighborhoods. Participants were asked to describe youth
      violence. Appropriate probes were used to explore similarities and differences by
      gender with regard to the reasons for violence. Definitions of youth violence
      were consistent across participants and included verbal threats, physical
      contact, and often the use of a weapon. Several common reasons for violence were
      found among both boys and girls; romantic relationships, respect, idle time,
      gangs/cliques, and witnessing violence. Reasons for violence unique to boys
      include fighting about issues related to money and illicit drugs. Gossip was
      identified as a reason specific to why girls engage in violence. Youth violence
      was perceived as a common problem impacting the lives of the boys and girls in
      this study. Although many of the reasons identified for violence are similar
      among boys and girls, select gender differences do exist. Future research and
      prevention efforts to address youth violence should engage young people in
      efforts to understand and address this important public health topic.

PMID- 15958787
TI  - Community experiences and perceptions related to demolition and gut
      rehabilitation of houses for urban redevelopment.
AB  - Reports about current residential demolition practices received from residents
      and plans for large-scale urban redevelopment in East Baltimore provided impetus
      for this study to assess community concerns and develop approaches to addressing
      them. This article describes the following themes regarding residents'
      experiences with demolition and gut rehabilitation of older housing performed as
      part of urban redevelopment: (1) lack of notification and awareness about
      protective measures; (2) concerns about environmental and safety hazards; (3)
      psychosocial impact from displacement, disruption in daily life, and inattention
      to community concerns; and (4) recommendations to improve redevelopment
      practices, including ideas to control neighborhood exposure to environmental
      hazards potentially exacerbated by residential demolition and gut rehabilitation.
      The findings from focus groups substantiated and deepened our understanding of
      earlier anecdotal reports of residents' concerns and emphasized the need for
      including community perceptions and ideas in addressing environmental and
      psychosocial issues related to urban redevelopment.

PMID- 15958789
TI  - Fifty-four new gene-based canine microsatellite markers.
AB  - Fifty-four new markers were developed to fill in gaps in the current map of
      canine microsatellites and to complement existing markers that may not be
      sufficiently informative in highly inbred canine pedigrees. Canine genes
      contained on the radiation hybrid map were used to obtain the sequence of the
      human homolog. A BLAST search versus the canine whole genome shotgun (wgs)
      sequence resource was used to obtain the sequence of the canine genomic contigs
      containing the homolog of the corresponding human gene. Canine sequences that
      contained microsatellites and mapped back to the correct location in the human
      genome were used to design primers for amplification of the microsatellites from
      canine genomic DNA. Heterozygosities of the markers were tested by genotyping
      grandparental DNAs obtained from the Nestle Purina Reference family DNA
      distribution center plus DNAs from unrelated Bouviers and Irish wolfhounds.
      Canine map positions of markers on the July 2004 freeze of the canine genome
      assembly were determined by in silico PCR or BLAST.

PMID- 15958788
TI  - Single nucleotide extension technology for quantitative site-specific evaluation
      of metC/C in GC-rich regions.
AB  - The development and use of high throughput technologies for detailed mapping of
      methylated cytosines (metC) is becoming of increasing importance for the
      expanding field of epigenetics. The single nucleotide primer extension reaction
      used for genotyping of single nucleotide polymorphisms has been recently adapted
      to interrogate the bisulfite modification induced 'quantitative' C/T polymorphism
      that corresponds to metC/C in the native DNA. In this study, we explored the
      opportunity to investigate C/T (and G/A) ratios using the Applied Biosystems
      (ABI) SNaPshot technology. The main effort of this study was dedicated to
      addressing the complexities in the analysis of DNA methylation in GC-rich regions
      where interrogation of the target cytosine can be confounded by variable degrees
      of methylation in other cytosines (resulting in variable C/T or G/A ratios after
      treatment with bisulfite) in the annealing site of the interrogating primer. In
      our studies, the mismatches of the SNaPshot primer with the target DNA sequence
      resulted in a biasing effect of up to 70% while these effects decreased as the
      location of the polymorphic site moved upstream of the target cytosine. We
      demonstrated that the biasing effect can be corrected with the SNaPshot primers
      containing degenerative C/T and G/A nucleotides. A series of experiments using
      various permutations of quantitative C/T and G/A polymorphisms at various
      positions of the target DNA sequence demonstrated that SNaPshot is able to
      accurately report cytosine methylation levels with <5% average SD from the true
      values. Given the relative simplicity of the method and the possibility to
      multiplex C/T and G/A interrogations, the SNaPshot approach may become a useful
      tool for large-scale mapping of metC.

PMID- 15958790
TI  - Characterization of candidate genes for neuronal ceroid lipofuscinosis in dog.
AB  - The neuronal ceroid lipofuscinoses (NCL) are a heterogenous group of monogenic
      autosomal recessive inherited progressive neurodegenerative diseases
      characterized by brain and retinal atrophy and the intracellular accumulation of
      autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and
      other cells. Until today, eight forms of NCL have been classified in humans by
      clinical criteria, which result from mutations in at least six different genes
      (TPP1, CLN2, PPT1, CLN5, CLN6, and CLN8). NCL has also been reported in various
      domestic animal species including cattle, goat, sheep, cat, and certain dog
      breeds. In this report, the experimental analysis of canine PPT1, CLN5, CLN6, and
      CLN8 full-length cDNA sequences is described, and the current whole genome
      sequence assembly was used for gene structure analyses. Characterization of the
      four canine genes revealed a conserved organization with respect to the human
      orthologs. In general the gene size in dog is smaller compared to the human
      sequence due to shorter intron length. Using four individuals of Tibetan terrier
      with NCL, and a single affected Polish Owczarek Nizinny (PON) dog, we excluded
      the complete coding region of canine PPT1 and CLN8 and three of four exons of
      CLN5 and six of seven exons of CLN6 harboring disease-causing mutations.

PMID- 15958791
TI  - Genetic mapping of canine multiple system degeneration and ectodermal dysplasia
      loci.
AB  - We characterized a movement disorder of Chinese Crested dogs clinically and
      pathologically indistinguishable from canine multiple system degeneration (CMSD)
      previously recognized in Kerry Blue Terriers. This fatal disease segregated as an
      autosomal recessive in a 51-dog pedigree of both breeds and their crosses. The
      occurrence of affected dogs among first-generation crosses demonstrated that the
      mutations causing multiple system degeneration in these breeds are allelic. The
      CMSD locus maps to CFA1 (LOD > 18) and haplotype analysis narrowed the CFA1
      target region to a 15-Mb segment that contains orthologs of genes on HSA6,
      including PARK2, the gene for the ubiquitin ligase parkin. Mutations in human
      PARK2 cause the most common form of familial Parkinson's disease, autosomal
      recessive juvenile parkinsonism, which has clinical and pathological similarities
      to canine multiple system degeneration. A second phenotype, canine ectodermal
      dysplasia (CED), segregated in the pedigree as an autosomal dominant with
      homozygous lethality. Dogs with ectodermal dysplasia have a sparse hair coat and
      abnormal dentition that is characteristic of the "hairless" variety of Chinese
      Cresteds. CED mapped to a region of CFA17 (LOD > 14) containing orthologs from
      HSA2. EDAR, the gene for the ectodysplasin A1 receptor, occurs on HSA2 but was
      excluded as the cause of canine ectodermal dysplasia.

PMID- 15958792
TI  - "Best friends" sharing the HMGA1 gene: comparison of the human and canine HMGA1
      to orthologous other species.
AB  - HMGA1 nonhistone proteins are reported to participate in various cellular
      processes including regulation of inducible gene transcription, integration of
      retroviruses into chromosomes, and the induction of neoplastic transformation and
      promotion of metastatic progression of cancer cells. Overexpression of HMGA1 was
      shown to be characteristic for various malignant tumors, suggesting a relation
      between the neoplastic phenotype and a high titer of the protein. Also
      chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in
      several tumors, e.g., uterine leiomyomas, pulmonary chondroid hamartomas, and
      follicular thyroid adenomas. We characterize the molecular structure of the
      canine HMGA1 cDNA, its splice variants, and predicted proteins HMGA1a and HMGA1b.
      Furthermore, we compared the CDS of both splice variants for 12 different breeds,
      screened them for SNPs, characterised a basic expression pattern, and mapped the
      gene via FISH. Additionally, we compared the known human, canine, murine, rat,
      hamster, bovine, pig, Xenopus, and chicken HMGA1 transcripts.

PMID- 15958793
TI  - Soybean phytophthora resistance gene Rps8 maps closely to the Rps3 region.
AB  - Root and stem rot is one of the major diseases of soybean. It is caused by the
      oomycete pathogen Phytophthora sojae. A series of resistance genes (Rps) have
      been providing soybean with reasonable protection against this pathogen. Among
      these genes, Rps8, which confers resistance to most P. sojae isolates, recently
      has been mapped. However, the most closely linked molecular marker was mapped at
      about 10 cM from Rps8. In this investigation, we attempted to develop a high
      density genetic map of the Rps8 region and identify closely linked SSR markers
      for marker-assisted selection of this invaluable gene. Bulk segregant analysis
      was conducted for the identification of SSR markers that are tightly linked to
      Rps8. Polymorphic SSR markers selected from the Rps8 region failed to show
      cosegregation with Phytophthora resistance. Subsequently, bulk segregant analysis
      of the whole soybean genome and mapping experiments revealed that the Rps8 gene
      maps closely to the disease resistance gene-rich Rps3 region.

PMID- 15958794
TI  - Chromosomal assignment of the canine melanophilin gene (MLPH): a candidate gene
      for coat color dilution in Pinschers.
AB  - Pinschers affected by coat color dilution show a specific pigmentation phenotype.
      The dilute pigmentation phenotype leads to a silver-blue appearance of the
      eumelanin-containing fur and a pale sandy color of pheomelanin-containing fur. In
      Pinscher breeding, dilute black-and-tan dogs are called "blue," and dilute red or
      brown animals are termed "fawn" or "Isabella fawn." Coat color dilution in
      Pinschers is sometimes accompanied by hair loss and a recurrent infection of the
      hair follicles. In human and mice, several well-characterized genes are
      responsible for similar pigment variations. To investigate the genetic cause of
      the coat color dilution in Pinschers, we isolated BAC clones containing the
      canine ortholog of the known murine color dilution gene Mlph. RH mapping of the
      canine MLPH gene was performed using an STS marker derived from BAC sequences.
      Additionally, one MLPH BAC clone was used as probe for FISH mapping, and the
      canine MLPH gene was assigned to CFA25q24.

PMID- 15958795
TI  - Exclusion of urate oxidase as a candidate gene for hyperuricosuria in the
      Dalmatian dog using an interbreed backcross.
AB  - Hyperuricosuria, an autosomal recessive disorder, is characterized by high levels
      of uric acid in the urine of Dalmatian dogs. Whereas high levels of uric acid are
      known to be caused by the silencing of the urate oxidase (uox) gene in humans and
      higher primates, the molecular basis for the Dalmatian defect is unknown.
      Transplantation studies show that the organ responsible for the Dalmatian
      phenotype is the liver, which is where urate oxidase is exclusively expressed and
      uric acid is converted into allantoin. We cloned and sequenced the canine uox
      cDNA and compared the sequence between a Dalmatian and non-Dalmatian dog. No
      change in cDNA sequence was identified. A Dalmatian x pointer backcross family
      was used to track the segregation of microsatellite markers surrounding the urate
      oxidase locus. The uox gene was excluded for Dalmatian hyperuricosuria based on
      the cDNA sequence identity and negative LOD scores.

PMID- 15958796
TI  - Spotting factor (Spf) from the Spotted-dilute system in maize is a member of the
      En/Spm controlling element family.
AB  - The Spotted-dilute controlling element system in maize involves an autonomous
      Spotting factor (Spf), and a receptor at the r1 locus haplotype R1-r(spotted
      dilute2). Its relationship with other maize transposable element systems is
      poorly characterized. Through development of a genetic tester that carries
      receptors for both the Spotted-dilute and the En/Spm controlling element systems,
      we determined that both receptors respond equally to Spf and En/Spm and that Spf
      is therefore a member of the En/Spm family of controlling elements.

PMID- 15958797
TI  - Inherited occipital hypoplasia/syringomyelia in the cavalier King Charles
      spaniel: experiences in setting up a worldwide DNA collection.
AB  - Inherited diseases commonly emerge within pedigree dog populations, often due to
      use of repeatedly bred carrier sire(s) within a small gene pool. Accurate family
      records are usually available making linkage analysis possible. However, there
      are many factors that are intrinsically difficult about collecting DNA and
      collating pedigree information from a large canine population. The keys to a
      successful DNA collection program include (1) the need to establish and maintain
      support from the pedigree breed clubs and pet owners; (2) committed individual(s)
      who can devote the considerable amount of time and energy to coordinating sample
      collection and communicating with breeders and clubs; and (3) providing means by
      which genotypic and phenotypic information can be easily collected and stored. In
      this article we described the clinical characteristics of inherited occipital
      hypoplasia/syringomyelia (Chiari type I malformation) in the cavalier King
      Charles spaniel and our experiences in establishing a pedigree and DNA database
      to study the disease.

PMID- 15958799
TI  - Before their time.

PMID- 15958798
TI  - Age-specific changes in epistatic effects on mortality rate in Drosophila
      melanogaster.
AB  - Models for the evolution of senescence assume that genes with age-specific
      effects act independently of one another. Although recent empirical data show
      that longevity is influenced in part by interactions between genes, there are
      currently few data on whether epistasis influences age-specific components of
      mortality. To gauge if and how interactions affect age-specific traits, we
      incorporated the Drosophila visible marker mutations ebony, forked, and purple
      into seven wild-caught strains of D. melanogaster to examine gene x genetic
      background interactions. We found significant natural genetic variation for
      longevity and baseline mortality rates. Gene x genetic background interactions
      were prevalent not only for longevity but also for baseline mortality rates and
      age-specific mortality rates. We conclude that gene x genetic background
      epistasis is prevalent for aging-related traits and could play a significant role
      in the evolution of aging. These results suggest that future genetic models for
      the evolution of aging should incorporate the effects of epistasis.

PMID- 15958800
TI  - Premature emission.

PMID- 15958801
TI  - Images in clinical medicine. Recurrent respiratory papillomatosis with lung
      involvement.

PMID- 15958802
TI  - The celestial fire of conscience -- refusing to deliver medical care.

PMID- 15958803
TI  - Taking their own lives -- the high rate of physician suicide.

PMID- 15958804
TI  - Bortezomib or high-dose dexamethasone for relapsed multiple myeloma.
AB  - BACKGROUND: This study compared bortezomib with high-dose dexamethasone in
      patients with relapsed multiple myeloma who had received one to three previous
      therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to
      receive either an intravenous bolus of bortezomib (1.3 mg per square meter of
      body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed
      by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose
      dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20
      for four five-week cycles, followed by treatment on days 1 through 4 for five
      four-week cycles. Patients who were assigned to receive dexamethasone were
      permitted to cross over to receive bortezomib in a companion study after disease
      progression. RESULTS: Patients treated with bortezomib had higher response rates,
      a longer time to progression (the primary end point), and a longer survival than
      patients treated with dexamethasone. The combined complete and partial response
      rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001),
      and the complete response rates were 6 percent and less than 1 percent,
      respectively (P<0.001). Median times to progression in the bortezomib and
      dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days),
      respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80
      percent among patients taking bortezomib and 66 percent among patients taking
      dexamethasone (P=0.003), and the hazard ratio for overall survival with
      bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75
      percent of patients treated with bortezomib and in 60 percent of those treated
      with dexamethasone. CONCLUSIONS: Bortezomib is superior to high-dose
      dexamethasone for the treatment of patients with multiple myeloma who have had a
      relapse after one to three previous therapies.

PMID- 15958805
TI  - Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7
      integrin.
AB  - BACKGROUND: Selective blockade of interactions between leukocytes and vascular
      endothelium in the gut is a promising strategy for the treatment of inflammatory
      bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo
      controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in
      patients with active ulcerative colitis. We randomly assigned 181 patients to
      receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an
      identical-appearing placebo intravenously on day 1 and day 29. Eligible patients
      also received concomitant mesalamine or no other treatment for colitis.
      Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated
      six weeks after randomization. RESULTS: Clinical remission rates at week 6 were
      33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02
      per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group,
      respectively (P=0.03). The corresponding proportions of patients who improved by
      at least 3 points on the ulcerative colitis clinical score were 66 percent, 53
      percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5
      mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had
      endoscopically evident remission, as compared with 8 percent of those receiving
      placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer
      greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor
      on circulating lymphocytes was observed and no benefit of treatment was
      identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective
      than placebo for the induction of clinical and endoscopic remission in patients
      with active ulcerative colitis.

PMID- 15958806
TI  - Survival after treatment of rabies with induction of coma.
AB  - We report the survival of a 15-year-old girl in whom clinical rabies developed
      one month after she was bitten by a bat. Treatment included induction of coma
      while a native immune response matured; rabies vaccine was not administered. The
      patient was treated with ketamine, midazolam, ribavirin, and amantadine. Probable
      drug-related toxic effects included hemolysis, pancreatitis, acidosis, and
      hepatotoxicity. Lumbar puncture after eight days showed an increased level of
      rabies antibody, and sedation was tapered. Paresis and sensory denervation then
      resolved. The patient was removed from isolation after 31 days and discharged to
      her home after 76 days. At nearly five months after her initial hospitalization,
      she was alert and communicative, but with choreoathetosis, dysarthria, and an
      unsteady gait.

PMID- 15958807
TI  - Prevalence and treatment of mental disorders, 1990 to 2003.
AB  - BACKGROUND: Although the 1990s saw enormous change in the mental health care
      system in the United States, little is known about changes in the prevalence or
      rate of treatment of mental disorders. METHODS: We examined trends in the
      prevalence and rate of treatment of mental disorders among people 18 to 54 years
      of age during roughly the past decade. Data from the National Comorbidity Survey
      (NCS) were obtained in 5388 face-to-face household interviews conducted between
      1990 and 1992, and data from the NCS Replication were obtained in 4319 interviews
      conducted between 2001 and 2003. Anxiety disorders, mood disorders, and substance
      abuse disorders that were present during the 12 months before the interview were
      diagnosed with the use of the American Psychiatric Association's Diagnostic and
      Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Treatment for
      emotional disorders was categorized according to the sector of mental health
      services: psychiatry services, other mental health services, general medical
      services, human services, and complementary-alternative medical services.
      RESULTS: The prevalence of mental disorders did not change during the decade
      (29.4 percent between 1990 and 1992 and 30.5 percent between 2001 and 2003,
      P=0.52), but the rate of treatment increased. Among patients with a disorder,
      20.3 percent received treatment between 1990 and 1992 and 32.9 percent received
      treatment between 2001 and 2003 (P<0.001). Overall, 12.2 percent of the
      population 18 to 54 years of age received treatment for emotional disorders
      between 1990 and 1992 and 20.1 percent between 2001 and 2003 (P<0.001). Only
      about half those who received treatment had disorders that met diagnostic
      criteria for a mental disorder. Significant increases in the rate of treatment
      (49.0 percent between 1990 and 1992 and 49.9 percent between 2001 and 2003) were
      limited to the sectors of general medical services (2.59 times as high in 2001 to
      2003 as in 1990 to 1992), psychiatry services (2.17 times as high), and other
      mental health services (1.59 times as high) and were independent of the severity
      of the disorder and of the sociodemographic characteristics of the respondents.
      CONCLUSIONS: Despite an increase in the rate of treatment, most patients with a
      mental disorder did not receive treatment. Continued efforts are needed to obtain
      data on the effectiveness of treatment in order to increase the use of effective
      treatments.

PMID- 15958808
TI  - Clinical practice. Chronic stable angina.

PMID- 15958809
TI  - Images in clinical Medicine. Bortezomib-induced skin lesions.

PMID- 15958810
TI  - Case records of the Massachusetts General Hospital. Case 18-2005. A 45-year-old
      woman with a painful mass in the abdomen.

PMID- 15958811
TI  - Bortezomib for myeloma -- much ado about something.

PMID- 15958812
TI  - Recovery from rabies.

PMID- 15958813
TI  - Transmission of rabies from an organ donor.

PMID- 15958814
TI  - What ails the FDA?

PMID- 15958815
TI  - Glycogen storage diseases and cardiomyopathy.

PMID- 15958816
TI  - Obesity and longevity.

PMID- 15958817
TI  - Triple HIV-1 infection.

PMID- 15958818
TI  - Significance and meaning of neurological signs in schizophrenia: two decades
      later.
AB  - OBJECTIVE: Patients with schizophrenia are characterized by neurological
      abnormalities, which can be assessed by bedside clinical examination. These
      abnormalities have been argued to represent core features of the illness. We
      review studies published since our last review in 1988 that address the validity
      of neurological signs as a trait feature of schizophrenia. METHODS: We conducted
      a literature search in the following computer databases: MEDLINE, PSYCHLIT,
      EMBASE, and COCHRANE. The search was limited to articles published from January
      1988 to May 2005. RESULTS: Neurological signs occur in the majority of patients
      with schizophrenia. Their occurrence is independent of demographic and most
      medication variables. Neurological signs are strongly associated with negative
      symptoms and cognitive impairments. There is also evidence to suggest that their
      occurrence is under genetic control. CONCLUSIONS: There is compelling evidence to
      suggest the hypothesis that neurological signs represent a trait feature of
      schizophrenia.

PMID- 15958819
TI  - Current and future challenges in anaemia management.

PMID- 15958820
TI  - Optimizing anaemia management with subcutaneous administration of epoetin.
AB  - European and US guidelines for renal anaemia management recommend subcutaneous
      (s.c.) epoetin as the preferred route of administration in pre-dialysis,
      peritoneal dialysis and haemodialysis patients. However, the restriction of
      Eprex/Erypro to intravenous (i.v.) administration in Europe has increased the
      interest of health care professionals regarding the optimal route of
      administration for all epoetin formulations. There are five major considerations
      for the 'optimal' route of epoetin administration: efficacy; dosing frequency;
      convenience; safety and tolerability; and cost. Although epoetin bioavailability
      is lower after s.c. administration, its efficacy is higher, owing to its
      prolonged elimination half-life compared with i.v. epoetin. Several studies and
      clinical surveys comparing s.c. and i.v. administration have demonstrated that
      equivalent target haemoglobin levels can be maintained at much lower doses of
      epoetin when administered s.c. Furthermore, s.c. epoetin dosing frequency can be
      reduced in some patients to once every 2 weeks, without compromising efficacy.
      Devices such as the Reco-Pen have been specifically designed to facilitate self
      administration of s.c. epoetin-beta. An upsurge in the incidence of pure red cell
      aplasia (PRCA) was linked to the epoetin-alpha product Eprex/Erypo in Europe, and
      an increase in PRCA cases of the same magnitude was not seen in patients taking
      other epoetin products s.c. Therefore, PRCA should not be used as an argument
      against s.c. administration. The reduced dose with s.c. administration of epoetin
      beta provides significant cost benefits, without compromising either safety or
      efficacy, and may also increase patient satisfaction and compliance with
      treatment.

PMID- 15958821
TI  - Managing a fateful alliance: anaemia and cardiovascular outcomes.
AB  - Cardiovascular disease (CVD) is a significant complication in chronic kidney
      disease (CKD) and a major cause of death in dialysis patients. Clinical studies
      have shown that anaemia is associated with reduced survival in patients with
      renal disease, heart failure or both. There is also evidence that, even in
      otherwise healthy individuals, anaemia is independently associated with an
      increased risk of CVD. The body adapts to anaemia by increasing cardiac output,
      which may result in cardiac remodelling and progression of left ventricular (LV)
      growth. Indeed, low haemoglobin (Hb) has been identified as an independent risk
      factor for LV growth in CKD patients, suggesting that there is a direct link
      between anaemia and adverse cardiac outcomes. This suggests that correction of
      anaemia with recombinant human erythropoietin (rhEPO; epoetin) may improve
      prognosis. Partial correction of anaemia produces partial regression of LV
      hypertrophy, while complete correction of anaemia can help to prevent LV
      dilatation in haemodialysis patients with normal LV volumes. Moreover, in non
      dialysis patients with advanced CVD, pilot studies showed that a moderate
      increase in Hb improved cardiac function and reduced hospitalization rates. In
      addition, consistent epoetin treatment before the start of dialysis was
      associated with a reduced risk of developing cardiac disease in CKD patients. In
      contrast, in dialysis patients with advanced cardiac disease, Hb normalization
      increased mortality risk. Therefore, early correction of anaemia appears
      important. The Cardiovascular risk Reduction by Early Anaemia Treatment with
      Epoetin beta (CREATE) study is investigating whether this approach is associated
      with a measurable reduction in cardiovascular risk.

PMID- 15958822
TI  - Managing anaemia and diabetes: a future challenge for nephrologists.
AB  - The combination of diabetes and chronic kidney disease is associated with
      increased mortality and reduced quality of life. Recent studies have shown that,
      in general, late referral of patients to the renal unit increases mortality, and
      that patients with diabetes who are referred late have a particularly poor
      prognosis. Several co-morbid conditions have been shown to contribute to poor
      patient outcomes, including both cardiovascular disease and anaemia. In patients
      with diabetic nephropathy, anaemia is more severe and is seen earlier than in
      patients with non-diabetic renal disease. Although the treatment of anaemia with
      recombinant human erythropoietin (rhEPO; epoetin) is well established, the only
      data currently available concerning the effects of early intervention in patients
      with diabetic nephropathy are from small-scale studies. Therefore, two large
      scale studies have been designed to provide information on the efficacy of
      epoetin treatment and on how current management strategies might be improved. The
      Anaemia CORrection in Diabetes (ACORD) study will provide information on the
      potential cardiac benefits of early anaemia management in patients with early,
      type 2 diabetic nephropathy. The Individualised Risk-profiling In DIabEtes
      Mellitus (IRIDIEM) study will provide evidence-based guidance in risk factor
      management, by assessing the efficacy of individualized interventions.

PMID- 15958823
TI  - Once weekly treatment with epoetin-beta.
AB  - Studies have shown that both intravenous (i.v.) and subcutaneous (s.c.)
      administration of epoetin-beta therapy are effective and well tolerated in the
      treatment of renal anaemia; however, the s.c. route provides enhanced efficacy
      with a lower dose compared with the i.v. route and it is more cost-effective.
      Epoetin dosing frequency is an important issue for health care professionals and
      patients. Recent studies have shown that epoetin-beta administered once weekly
      and once every 2 weeks can maintain stable target haemoglobin and haematocrit
      levels in dialysis patients. Such reduced dosing frequencies may improve patient
      satisfaction and compliance with treatment, and encourage patients to self
      administer. Furthermore, less frequent dosing administration would be associated
      with economic benefits in terms of reduced nursing time in the clinic or out
      patient setting. Where this is clinical practice, fewer injections and visits to
      the clinic should also improve patients' quality of life. A range of effective
      dosing regimens with epoetin-beta administered via either pre-filled syringes,
      multidose vials or injector pens allows physicians to tailor treatment to an
      individual patient's preference.

PMID- 15958824
TI  - Factors influencing the immunogenicity of therapeutic proteins.
AB  - Several diseases and disorders are treatable with therapeutic proteins, but some
      of these products may induce an immune response, especially when administered as
      multiple doses over prolonged periods. Antibodies are created by classical immune
      reactions or by the breakdown of immune tolerance; the latter is characteristic
      of human homologue products. Many factors influence the immunogenicity of
      proteins, including structural features (sequence variation and glycosylation),
      storage conditions (denaturation, or aggregation caused by oxidation),
      contaminants or impurities in the preparation, dose and length of treatment, as
      well as the route of administration, appropriate formulation and the genetic
      characteristics of patients. The clinical manifestations of antibodies directed
      against a given protein may include loss of efficacy, neutralization of the
      natural counterpart and general immune system effects (including allergy,
      anaphylaxis or serum sickness). An upsurge in the incidence of antibody-mediated
      pure red cell aplasia (PRCA) among patients taking one particular formulation of
      recombinant human erythropoietin (epoetin-alpha, marketed as Eprex(R)/Erypo(R);
      Johnson & Johnson) in Europe caused widespread concern. The PRCA upsurge
      coincided with removal of human serum albumin from epoetin-alpha in 1998 and its
      replacement with glycine and polysorbate 80. Although the immunogenic potential
      of this particular product may have been enhanced by the way the product was
      stored, handled and administered, it should be noted that the subcutaneous route
      of administration does not confer immunogenicity per se. The possible role of
      micelle (polysorbate 80 plus epoetin-alpha) formation in the PRCA upsurge with
      Eprex is currently being investigated.

PMID- 15958825
TI  - Dose tailoring strategies in haemodialysis patients: a discussion of case
      histories.
AB  - Tailoring of the epoetin dose to the needs, clinical condition and circumstances
      of individual patients with renal anaemia offers potential for optimizing the
      benefits and costs of epoetin therapy. This can be achieved through alterations
      to dosing frequency, administration route and/or delivery device. Two case
      histories are presented to illustrate dose tailoring of epoetin therapy in daily
      clinical practice. The first patient was a man aged 23 years with renal failure
      secondary to vasculitis. Haemoglobin (Hb) levels were stable during treatment
      with subcutaneous (s.c.) epoetin-beta. Switching to intravenous (i.v.) epoetin
      beta required, after a 5 month period of complex dose adjustments, a 50% increase
      in the dose of epoetin-beta to maintain Hb levels. The second patient was a woman
      aged 50 years with diabetic nephropathy. She self-administered epoetin-beta via
      the Reco-Pen device to maintain stable Hb levels. Epoetin-beta is approved for
      administration at dosing frequencies ranging from three times weekly to once
      every 2 weeks, is safe and effective whether administered by the s.c. or i.v.
      route and is available in a range of delivery devices. Epoetin-beta therapy can
      be easily tailored according to the needs, preferences and circumstances of
      individual patients, thereby maximizing treatment outcomes.

PMID- 15958826
TI  - Individualizing anaemia treatment: a discussion of case histories.
AB  - Current guidelines give evidence-based advice on how best to manage anaemia in
      patients with renal disease, but these guidelines do not consider individual
      patient needs, so tailoring anaemia management to each patient still remains a
      challenge for the treating physician. Two case studies are described that
      illustrate some of the key factors that need to be considered. The first case
      emphasizes that haemoglobin (Hb) targets recommended in current guidelines may
      not suit all patients. The patient had been stably maintained on subcutaneous
      epoetin therapy with an average Hb concentration of >13.0 g/dl because he
      developed angina symptoms when his Hb level fell to 12.2 g/dl. Iron deficiency
      was identified as the likely cause of falling Hb in this patient. After the
      patient's iron supplementation was increased, his Hb level was normalized back to
      >13.0 g/dl without increasing the epoetin dose, and the angina symptoms were
      resolved. The second case involved a pre-dialysis patient with diabetes, who
      required a higher dose of epoetin after beginning concomitant antihypertensive
      treatment with an angiotensin-converting enzyme inhibitor. Previously, the
      treatment of renal anaemia in pre-dialysis patients has not been the focus of
      attention. Two ongoing randomized controlled trials have been designed to study
      early initiation of epoetin treatment in pre-dialysis patients and will provide
      much needed information in this area.

PMID- 15958830
TI  - The potential for interactions between antimalarial and antiretroviral drugs.

PMID- 15958831
TI  - Pertussis toxin B-oligomer dissociates T cell activation and HIV replication in
      CD4 T cells released from infected lymphoid tissue.
AB  - OBJECTIVE: To investigate, in human lymphoid tissue infected with HIV-1 ex vivo,
      the immunostimulatory and HIV inhibitory properties of pertussis toxin B oligomer
      (PTX-B) and of the genetically modified non-toxic PT-9K/129G. METHODS: Human
      tonsils from uninfected donors were infected ex vivo with R5 or X4 HIV-1 in the
      presence or absence of PTX-B. Virus replication was evaluated in culture
      supernatants; cells emigrated from tissue blocks were immunostained for
      lymphocytic and activation markers. HIV DNA and cell proliferation were evaluated
      with real-time PCR and [H]thymidine incorporation, respectively. RESULTS: Both
      PTX-B and PT-9K/129G inhibited HIV-1 replication. These compounds activated and
      stimulated the proliferation of emigrated cells, most of which were CD4 T
      lymphocytes. Cells emigrated from infected tissues did not produce detectable
      virus in unstimulated or in PTX-B- or PT-9K/129G-stimulated cultures whereas
      robust virus production was triggered by phytohemagglutinin (PHA) or interleukin
      2 (IL-2). Analysis of HIV DNA content indicated that infected cells were present
      among emigrated cells and that their number greatly increased following IL-2
      stimulation, whereas it remained constant in the presence of PTX-B or PT-9K/129G.
      CONCLUSIONS: PTX-B and PT-9K/129G inhibit both R5 and X4 HIV-1 replication in
      human lymphoid tissue ex vivo. In contrast to PHA and IL-2, they promote the
      proliferation of CD4 T lymphocytes emigrated from tissue, including HIV-infected
      cells, without triggering virus replication. Therefore, these emigrated CD4 T
      cells represent a novel model of a latent inducible HIV reservoir. Thus, PTX-B
      and the clinically approved PT-9K/129G are potential antiretroviral agents
      endowed with immunostimulatory capacity.

PMID- 15958832
TI  - Genotypes at chromosome 22q12-13 are associated with HIV-1-exposed but uninfected
      status in Italians.
AB  - OBJECTIVE: Despite multiple and repeated exposures to HIV-1, some individuals
      possess no detectable HIV genome and show T-cell memory responses to the viral
      antigens. HIV-1-reactive mucosal IgA detected in such uninfected individuals
      suggests their possible immune resistance against HIV. We tested if the above HIV
      1-exposed but uninfected status was associated with genetic markers other than a
      homozygous deletion of the CCR5 gene. METHODS: Based on our mapping in chromosome
      15 of a gene controlling the production of neutralizing antibodies in a mouse
      retrovirus infection, we genotyped 42 HIV-1-exposed but uninfected Italians at
      polymorphic loci in the syntenic segment of human chromosome 22, and compared
      them with 49 HIV-1-infected and 47 uninfected healthy control individuals by a
      closed testing procedure. RESULTS: A significant association was found between
      chromosome 22q12-13 genotypes and a putative dominant locus conferring anti-HIV-1
      immune responses in the exposed but uninfected individuals. Distributions of
      linkage disequilibrium across chromosome 22 also differed between the exposed but
      uninfected and two other phenotypic groups. CONCLUSIONS: The data indicated the
      presence of a new genetic factor associated with the HIV-1-exposed but uninfected
      status.

PMID- 15958833
TI  - Cytomegalovirus rather than HIV triggers the outgrowth of effector
      CD8+CD45RA+CD27- T cells in HIV-1-infected children.
AB  - OBJECTIVE: To analyse the effect of viral coinfections on immune reconstitution
      in HIV-1-infected children (< 18 years) taking highly active antiretroviral
      therapy (HAART). METHODS: Absolute lymphocyte numbers of various subsets of CD8 T
      cells were measured. RESULTS: Prior cytomegalovirus (CMV) infection correlated
      with an increased number of CD8 effector T cells (i.e., CD45RA+CD27-) at baseline
      (CMV-seropositive versus CMV-seronegative patients; P = 0.009), as well as an
      increased state of T cell activation as defined by HLA-DR and CD38 expression.
      The expansion of effector CD8 T cells persisted over time, independent of the HIV
      response to HAART. Numbers of CD8 effector T cells were significantly higher in
      patients with CMV replication as reflected by persistent urinary CMV shedding and
      periodic CMV DNAaemia (P = 0.02). These patients also showed an increase in CMV
      specific antibodies compared with those without CMV shedding (P = 0.007). The
      number of CMV-specific interferon-gamma (IFN-gamma)-producing CD8 T cells was
      lower in children who persistently shed CMV compared with those who did not (P =
      0.02). In contrast, CMV-specific CD4 T cell responses were detected at similar
      levels in both groups. CONCLUSIONS: In HIV-1-infected children, CMV infection
      correlated with the outgrowth of CD8+CD45RA+CD27- effector T cells. Activation of
      the immune system by persistent CMV secretion resulted in increasing CMV-specific
      IgG and higher numbers of CD8 effector T cells. Despite these increases, the CMV
      specific IFN-gamma-producing CD8 T cell response was diminished, which could
      explain the inability to suppress CMV completely in 41% of HIV-1-infected
      children.

PMID- 15958834
TI  - Cotrimoxazole prophylaxis by HIV-infected persons in Uganda reduces morbidity and
      mortality among HIV-uninfected family members.
AB  - BACKGROUND: The effect of cotrimoxazole prophylaxis taken by persons with HIV on
      community health and antimicrobial resistance is unknown. OBJECTIVE: To assess
      the effect of cotrimoxazole prophylaxis taken by persons with HIV on morbidity,
      mortality, and antimicrobial resistance of diarrheal pathogens infecting their
      HIV-negative family members. DESIGN: Prospective cohort in rural Uganda. METHODS:
      A total of 879 persons with HIV and 2771 HIV-negative family members received
      weekly home-visits. After 5 months, persons with HIV received daily cotrimoxazole
      prophylaxis and households were followed for an average of 17 additional months.
      FINDINGS: During the study, 224 participants with HIV (25%) and 29 household
      members (1%) died. Mortality among HIV-negative family members < 10 years old was
      63% less during the cotrimoxazole period than before [hazard ratio, 0.37; 95%
      confidence interval (CI), 0.14-0.95; P = 0.04]. Malaria among family members was
      less common during cotrimoxazole treatment [incidence rate ratio (IRR), 0.62; CI,
      0.53-0.74; P < 0.0001], as were diarrhea (IRR, 0.59; CI, 0.45-0.76; P = 0.0001),
      and hospitalizations (IRR, 0.57; CI, 0.36-0.92; P = 0.02). Death of a parent with
      HIV was associated with a threefold increase in mortality among HIV-negative
      children < 10 years old (hazard ratio, 2.9; CI, 1.1-8.1; P = 0.04). Of 134
      bacterial isolates from family members before cotrimoxazole treatment, 89 (66%)
      were resistant to cotrimoxazole; of 75 recovered during cotrimoxazole treatment,
      54 (72%) were resistant (P = 0.41). INTERPRETATION: Cotrimoxazole prophylaxis
      taken by persons with HIV was associated with decreased morbidity and mortality
      among family members. Antimicrobial resistance among diarrheal pathogens
      infecting family members did not increase. Concerns regarding the spread of
      bacterial resistance should not impede implementation of cotrimoxazole programs.

PMID- 15958835
TI  - Incidence and risk factors of immune reconstitution inflammatory syndrome
      complicating HIV-associated cryptococcosis in France.
AB  - BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in association
      with cryptococcosis has been anecdotically reported following administration of
      highly active antiretroviral therapy (HAART). OBJECTIVE: To analyse the incidence
      and risk factors for IRIS-associated cryptococcosis among HIV-infected patients.
      DESIGN: Retrospective multicentre study between 1996 and 2000 through the French
      Cryptococcosis Database. METHODS: Subsequent occurrence of IRIS examined in 120
      HIV-infected adult patients treated with HAART and experiencing a first episode
      of culture-confirmed cryptococcosis. RESULTS: Ten patients developed IRIS during
      the study period, giving an incidence of 10/239, or 4.2/100 person-years [95%
      confidence interval (CI), 2.2-7.8]. IRIS consisted of acute symptoms consistent
      with inflammation occurring within a median of 8 months (range, 2-37) after the
      diagnosis of cryptococcosis in the context of negative cultures and immunological
      and/or virological response to HAART. Radiology and histopathology detected
      features compatible with inflammation. Symptom severity required transfer into
      intensive care units for three patients and use of anti-inflammatory drugs for
      four. Three patients with evolutive IRIS died. Compared with patients without
      IRIS for whom complete clinical and microbiological information were available at
      baseline, previously unknown HIV infection [odds ratio (OR), 4.8; 95% CI, 1.0
      21.7], CD4 cell count < 7 x 10 cells/l (OR, 4.0; 95% CI, 0.9-17.2), fungaemia
      (OR, 6.1; 95% CI, 1.1-35.2) and HAART initiation within 2 months of
      cryptococcosis diagnosis (OR, 5.50; 95% CI, 1.0-29.6) were independently
      associated with the risk of subsequent IRIS. CONCLUSIONS: IRIS-related
      cryptococcosis was observed more frequently in severely immunocompromised
      patients with disseminated infection and HAART initiation soon after the
      diagnosis.

PMID- 15958836
TI  - Substitution of nevirapine or efavirenz for protease inhibitor versus lipid
      lowering therapy for the management of dyslipidaemia.
AB  - OBJECTIVES: To evaluate simplified protease inhibitor (PI)-sparing antiretroviral
      treatment versus lipid-lowering therapy for the management of highly active
      antiretroviral therapy (HAART)-induced hyperlipidaemia. DESIGN: Randomized, open
      label clinical trial assessing the efficacy on hyperlipidaemia of a switching
      therapy from PI to non-nucleoside reverse transcriptase inhibitor (NNRTI)
      nevirapine or efavirenz versus a hypolipidaemic treatment (with pravastatin or
      bezafibrate) added to current, unchanged antiretroviral combination. METHODS: All
      HIV-infected patients on their first HAART regimen, with stable immuno
      virological features, naive to all NNRTIs, and with mixed hyperlipidaemia, were
      randomized to replace PI with nevirapine (arm A) or efavirenz (arm B), or to
      receive pravastatin (arm C) or bezafibrate (arm D) with unchanged HAART regimen,
      and were followed-up for 12 months. RESULTS: One hundred and thirty patients were
      evaluated: 29 patients were randomized to arm A, 34 to arm B, 36 to arm C, and 31
      to arm D. At the end of the 12-month follow-up, a reduction of 25.2, 9.4, 41.2
      and 46.6% in mean triglyceridaemia versus respective baseline values was reported
      in groups A, B, C and D, respectively, with statistically significant difference
      between arms A-B and C-D (P < 0.01). Similar results were reported for total and
      low-density lipoprotein cholesterol levels. Viro-immunological efficacy and
      tolerability profile were comparable in all considered arms. CONCLUSION:
      Pravastatin and bezafibrate proved significantly more effective in the management
      of HAART-related hyperlipidaemia than the switching therapy from PI to nevirapine
      or efavirenz.

PMID- 15958837
TI  - Indinavir protein-free concentrations when used in indinavir/ritonavir
      combination therapy.
AB  - OBJECTIVE: To describe the in vivo protein-binding characteristics of indinavir
      (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma
      concentrations. DESIGN: The ACTG protocol 5055 was a multicenter study comparing
      the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg
      twice daily in HIV-infected adults. METHODS: Forty-four patients underwent a 12-h
      intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma
      samples from 35 patients at Cmax, 6 and 12 h post dose were used to determine the
      unbound IDV concentrations. Unbound IDV was separated in plasma samples using
      ultra-filtration and measured using high-performance liquid chromatography with
      UV detection. RESULTS: Mean IDV protein-bound fraction across all time points in
      the 800/200 and 400/400 arm were 53.4 and 51.8%, respectively. In the 800/200
      arm, percentage binding at Cmax was 50% compared with 56% at 12 h (P = 0.008). In
      the 400/400 arm, percentage binding at Cmax was 49% compared with 54% at 12 h (P
      = 0.008). CONCLUSIONS: The extent of plasma protein binding of IDV in this study
      was less than in previously published data with IDV alone. Although IDV
      concentrations differed across the arms, the percentage of IDV protein binding at
      all time points was not different between the 800/200 and 400/400 arms. However,
      the percentage of IDV protein binding at Cmax was significantly lower compared
      with 12 h in each arm, possibly suggesting that IDV protein binding is
      concentration-dependent. These data suggest that RTV affects IDV protein-binding
      characteristics and IDV also exhibits concentration dependent binding when
      administered with RTV.

PMID- 15958838
TI  - HIV-1 intermittent viraemia in patients treated by non-nucleoside reverse
      transcriptase inhibitor-based regimen.
AB  - BACKGROUND: It has been demonstrated that, in patients treated by protease
      inhibitor-based regimen, intermittent viraemia occurred frequently and was
      associated with higher concentrations of residual replication but not with
      virological failure. Risk factors associated with intermittent viraemia and its
      impact in patients treated by non-nucleoside-reverse-transcriptase-inhibitor
      based (NNRTI) regimen need to be evaluated. METHODS: We analyzed the occurrence
      of blips (one HIV-1 RNA > 50 copies/ml with a subsequent value < 50 copies/ml),
      the level of these blips (between 3 and 50 copies/ml) and their effect on CD4
      cell count and the occurrence of virological failure in 43 patients with stable
      suppression of HIV-1 plasma viraemia (< 50 copies/ml) under NNRTI-based therapy.
      RESULTS: Eight out of 43 patients had one episode of blips during the follow-up
      (median = 350 copies/ml). Comparing patients with and without blips, the median
      level of HIV-1 RNA at baseline was 7.5 versus 3 copies/ml (P = 0.008),
      respectively. Patients with blips had a significantly lower CD4 cell count after
      12 and 18 months than the others. Plasma concentrations of NNRTI before, during,
      and after the blips were adequate. In addition, the occurrence of blips was not
      associated with virological failure. CONCLUSION: These results suggest that blips
      may reflect ongoing viraemia of below 50 copies/ml and can impair the CD4 cell
      count recovery under an NNRTI regimen. The impairment of CD4 cell count recovery
      seems to be affected more by the occurrence of blips than by the level of
      viraemia (< 50 copies/ml) itself. Nevertheless, despite a tight genetic barrier
      for resistance with NNRTI drugs, no virologic failure occurred during the follow
      up.

PMID- 15958839
TI  - Maternal and infant factors and lymphocyte, CD4 and CD8 cell counts in uninfected
      children of HIV-1-infected mothers.
AB  - OBJECTIVE: To evaluate the effects of antiretroviral treatment (ART) for mother
      to-child transmission of HIV and infant/maternal characteristics on total
      lymphocytes (TLC) and lymphocyte subsets in uninfected children of HIV-1-infected
      mothers. DESIGN: The European Collaborative Study followed 1663 uninfected
      children from birth until at least 8 years of age using a standard protocol.
      METHODS: Smoothers (running medians) illustrated patterns of immune markers over
      age by ART exposure and race. Associations between lymphocyte parameters and
      maternal/infant characteristics were quantified in linear regression analyses
      using z-scores obtained after modelling log10-transformed TLC, CD4 and CD8 cell
      counts using the LMS method. Cox proportional hazard models assessed time to TLC,
      CD4 and CD8 cell counts below the defined cut-off. Covariates included
      prematurity, gender, race, drug withdrawal and ART exposure. RESULTS: Overall,
      black children had lower TLC, CD4 and CD8 cell counts than white children, and an
      increased risk of TLC, CD4 and CD8 cell counts below the cut-off. ART exposure
      was associated with TLC levels (but not with TLC below the cut-off for
      lymphopenia), with reduced CD4 cell counts in the first year of life, and with
      reduced CD8 cell counts until at least 8 years of age. Duration and intensity of
      ART exposure was associated with TLC levels. CONCLUSION: The effect of ART
      exposure in fetal and early life on TLC and CD8 cell counts was prolonged until
      at least 8 years. These results add to the growing list of adverse effects
      associated with ART used as prevention of mother-to-child transmission of HIV.

PMID- 15958840
TI  - Multiple drug class-wide resistance associated with poorer survival after
      treatment failure in a cohort of HIV-infected patients.
AB  - OBJECTIVE: To evaluate the effect of drug class-wide resistance (CWR) on survival
      in HIV-infected individuals who underwent genotypic resistance test after
      antiretroviral failure. DESIGN: Observational, longitudinal cohort study.
      METHODS: HIV-infected individuals experiencing treatment failure were enrolled at
      first genotypic resistance test. End-points were death for any cause, AIDS
      related death and AIDS-defining event/death. CWR was defined according to the
      International AIDS Society consensus. Survival analysis was performed with Cox's
      model. RESULTS: Among 623 patients enrolled and followed for a median of 19
      months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48
      months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7,
      13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively,
      for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new
      AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous
      AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval,
      1.76-16.24) were all significantly associated with increased risk of death, while
      higher CD4 cell count and use of a new boosted protease inhibitor drug after
      identifying genotypic resistance were associated with reduced risk. Detection of
      three CWR was also significantly associated with higher risk of AIDS-related
      death and new AIDS event/death. CONCLUSIONS: Even in the late era of highly
      effective antiretroviral treatments, detection of CWR, particularly if extended
      to all three drug classes is related to poorer clinical outcome and represents a
      risk-marker of disease progression and death.

PMID- 15958841
TI  - SEN virus has an adverse effect on the survival of HIV-positive patients.
AB  - BACKGROUND: Patients infected with HIV are often coinfected with other viruses.
      OBJECTIVE: To investigate the effect of SEN virus (SENV) strains D and H on
      mortality in HIV-positive patients. METHODS: A total of 217 HIV-positive patients
      were analysed retrospectively after first presentation and blood sampling
      (January 1997 to July 1997) and the effect of coinfection with SENV-D and SENV-H
      on survival was examined. Analysis periods were the time from blood sampling to
      the end of follow-up, and the time from diagnosis of HIV infection to the end of
      study follow-up. SENV-H DNA was measured quantitatively. Prevalences of SENV-D
      and SENV-H were compared with those in 112 healthy blood donors. RESULTS: SENV
      prevalence was significantly higher in HIV-positive patients than in controls
      (56/217 and 12/112, respectively; P < 0.001). SENV positivity had no influence on
      survival, but a significant negative influence of SENV-H on survival was observed
      when SENV-H DNA was > 530 copies/ml, which was the mean SENV-H DNA level found in
      HIV-negative controls. This adverse effect was found for both studied time
      periods in a Kaplan-Meier analyses. A multivariate Cox regression analysis,
      including CD4 cell count, Centers for Disease Control and Prevention stage, age,
      sex, HIV RNA, highly active antiretroviral therapy and hepatitis C virus status,
      revealed that a high SENV DNA level was an independent risk factor or indicator
      for adverse disease outcome. CONCLUSION: SENV infection is common in HIV-positive
      patients. High SENV-H DNA levels were predictive for poor survival in HIV
      positive patients.

PMID- 15958842
TI  - A new meeting place: chatting on the Internet, e-dating and sexual risk behaviour
      among Dutch men who have sex with men.
AB  - OBJECTIVE: To describe the process of Internet chatting, and subsequent dating
      and sexual (risk) behaviour among Dutch men who have sex with men (MSM), and to
      compare the demographic profile of the Internet sample with a traditional Dutch
      MSM sample. DESIGN: A self-selected anonymous Internet sample. METHODS: Enrolment
      via a prominent gay chat room. Potential respondents were asked to complete an
      online questionnaire about chatting and dating, and sexual (risk) behaviour with
      their last date via chatting (e-date). In 26 days, 5302 questionnaires were
      returned. Of these, 4984 were evaluated as reliable and were used in the
      analyses. RESULTS: Eighty-two per cent chatted at least once a week, 88% had ever
      dated through chatting, and of these 89% had had sex with one or more e-dates.
      With respect to the last e-date, almost 50% had had anal sex with their last e
      date, and 15% reported unprotected anal sex. Especially among HIV-positive men, a
      high percentage of unprotected anal sex was reported (39%). After correcting for
      the disclosure of HIV status, this percentage remained twice as high compared
      with HIV-negative and never-tested men (28 versus 14%). Compared with a
      traditional MSM sample, the Internet sample was significantly younger, and
      comprised more non-Dutch and bisexual men, whereas the level of sexual risk
      behaviour with casual partners was comparable. CONCLUSION: The Internet is a
      popular new meeting place for MSM, and attracts men with a different demographic
      profile. The level of risk behaviour warrants that opportunities for
      interventions on the Internet are explored, with special attention to HIV
      positive chatters.

PMID- 15958843
TI  - Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients
      receiving protease inhibitors: a pilot study.
AB  - Sixteen HIV-infected patients with protease inhibitor (PI)-related, persisting
      hypercholesterolaemia were treated with 10 mg a day rosuvastatin for 24 weeks. At
      the end of the observation period, the median reductions in total cholesterol and
      triglyceride levels versus median baseline values were 21.7 and 30.1%,
      respectively (P < 0.01). In our small pilot study, rosuvastatin was found to be
      effective for the treatment of PI-associated hyperlipidaemia, in association with
      a favourable tolerability profile, without significant clinical or laboratory
      adverse events.

PMID- 15958844
TI  - Pharmacokinetics of once-daily lopinavir/ritonavir and the influence of dose
      modifications.
AB  - We studied the pharmacokinetics of lopinavir/ritonavir dosed at 800/200 mg a day
      in 20 HIV-1-infected patients, and evaluated the effect of dose modifications in
      the case of trough concentration (Ctrough) levels less than 1.0 mg/l. Ctrough
      levels after the daily administration of lopinavir/ritonavir were lower than with
      twice daily administration. Dose modifications in four patients with Ctrough
      levels less than 1.0 mg/l succeeded in only one patient. Therapeutic drug
      monitoring can identify patients with lower-than-expected lopinavir exposure in a
      larger study.

PMID- 15958845
TI  - Risk factors for CD4 lymphopenia in patients treated with a tenofovir/didanosine
      high dose-containing highly active antiretroviral therapy regimen.
AB  - In this study, the dynamics of CD4 cell depletion during tenofovir/didanosine co
      administration were analysed. Ninety-five HIV-positive patients were followed for
      562 days, and 37 lost at least 50 CD4 cells, with a median delay of 274 days. Cox
      analysis showed that the CD4 cell decrease was associated with a duration of
      treatment by didanosine of more than 853 days and a didanosine dose of more than
      5.50 mg/kg.

PMID- 15958846
TI  - Pravastatin does not have a consistent antiviral effect in chronically HIV
      infected individuals on antiretroviral therapy.

PMID- 15958847
TI  - HIV-related thrombocytopenic purpura not relapsing during CD4 cell-guided
      treatment interruptions.

PMID- 15958848
TI  - Soft tissue perineurioma: clinicopathologic analysis of 81 cases including those
      with atypical histologic features.
AB  - Perineuriomas are uncommon benign peripheral nerve sheath tumors that include
      soft tissue, sclerosing, and intraneural variants. Fewer than 50 soft tissue
      perineuriomas have been reported to date, and the clinical significance of
      atypical histologic features is unknown. To characterize these tumors further, 81
      soft tissue perineuriomas received between 1994 and 2003 were retrieved from the
      authors' consult files. Hematoxylin and eosin sections were reexamined,
      immunohistochemistry was performed, and clinical details were obtained from
      referring physicians. Forty-three patients were female and 38 male (mean age, 46
      years; range, 10-79 years). Tumor size ranged from 0.3 to 20 cm (mean, 4.1 cm) in
      greatest dimension. Most patients presented with a painless mass. The tumors
      arose in a wide anatomic distribution: 36 lower limb, 19 upper limb, 15 trunk, 7
      head and neck, 3 retroperitoneum, and 1 paratesticular. Forty-two tumors were
      situated primarily in subcutis, 25 in deep soft tissue, and 9 were limited to the
      dermis. Nearly all cases were grossly well circumscribed; 12 showed focal
      microscopically infiltrative margins. Most tumors had a storiform and focally
      whorled growth pattern; 17 exhibited fascicular areas. Thirty-eight tumors were
      hypocellular, 15 were markedly hypercellular, and 7 showed alternating zones of
      hypocellularity and hypercellularity. Stroma was usually collagenous but in 17
      tumors was predominantly myxoid, and in 16 was mixed collagenous and myxoid.
      Mitoses ranged from 0 to 13 per 30 high power fields (mean, 1); 53 tumors had no
      mitoses. Based on worrisome cytologic or architectural features, 14 cases were
      classified as atypical perineuriomas: 12 contained scattered pleomorphic cells, 1
      showed an abrupt transition from typical morphology to a markedly hypercellular,
      fascicular area with cytologic atypia, and 1 exhibited diffuse infiltration of
      skeletal muscle. All tumors were reactive for epithelial membrane antigen; 50 of
      78 (64%) expressed CD34, 22 of 76 (29%) claudin-1, 16 of 77 (21%) smooth muscle
      actin, and 4 of 81 (5%) S-100 protein. All tumors were negative for glial
      fibrillary acidic protein, neurofilament protein, and desmin. Clinical follow-up
      was available for 43 patients (mean, 41 months; range, 6-146 months). Among
      tumors for which the status of surgical margins was known, 52% were widely
      excised, 31% were marginally excised, and 18% had positive margins. Only two
      tumors recurred locally (one of which was atypical): one recurred 10 years
      following primary excision; and one recurred twice, 5 and 9 years following
      excision. No tumor metastasized. Soft tissue perineuriomas behave in a benign
      fashion and rarely recur. Atypical histologic features (including scattered
      pleomorphic cells and infiltrative margins) seem to have no clinical significance
      and appear to be akin to those seen in ancient schwannoma and atypical (bizarre)
      neurofibroma.

PMID- 15958849
TI  - Intestinal perineuriomas: clinicopathologic definition of a new anatomic subset
      in a series of 10 cases.
AB  - Benign peripheral nerve sheath tumors are uncommon in the gastrointestinal tract,
      and perineuriomas have not previously been reported to occur at this anatomic
      location. In this study, we analyzed the clinicopathologic and
      immunohistochemical features of 10 perineuriomas arising in the intestine. Eight
      patients were female and 2 male (median age, 51 years; range, 35-72 years). Eight
      of the lesions were intramucosal perineuriomas presenting as small sessile polyps
      detected during colonoscopy; 6 of these 8 patients were asymptomatic and
      undergoing colorectal cancer screening. The remaining 2 cases were submucosal
      masses, one each located in the colon and jejunum. Of the mucosal polyps, six
      were located in the rectosigmoid or sigmoid colon and one each was detected in
      the descending colon and transverse colon. The polyps ranged from 0.2 to 0.6 cm
      (median, 0.4 cm) in greatest dimension. The colonic and jejunal masses measured 3
      cm and 4.5 cm, respectively. Histologically, the intramucosal perineuriomas were
      composed of uniform bland spindle cells having ovoid to elongated nuclei and pale
      indistinct cytoplasm, with no cytologic atypia, pleomorphism, or mitotic
      activity. The lesions had a fine collagenous stroma, demonstrated irregular
      borders with the adjacent lamina propria, and entrapped colonic crypts. Five
      cases exhibited hyperplastic changes in the adjacent or entrapped epithelium. The
      colonic submucosal tumor was microscopically well circumscribed, whereas the
      jejunal perineurioma showed focal infiltration through the muscularis propria
      into the subserosa. The stroma was collagenous in the colonic tumor and
      predominantly myxoid in the jejunal tumor. The spindle cells in the submucosal
      perineuriomas demonstrated tapered nuclei and elongated bipolar cytoplasmic
      processes. All tumors except one were positive for epithelial membrane antigen
      (EMA); 4 of 10 expressed claudin-1 and 2 of 10 expressed CD34. All tumors were
      negative for S-100 protein, glial fibrillary acidic protein, neurofilament
      protein, smooth muscle actin, desmin, caldesmon, KIT, and pan-keratin. Electron
      microscopy was performed on the tumor lacking EMA expression, revealing typical
      features of perineurioma, namely, spindle cells with long bipolar cytoplasmic
      processes and prominent pinocytotic vesicles, surrounded by discontinuous basal
      lamina. Clinical follow-up was available for 4 patients (median, 34 months;
      range, 8-53 months). No tumor recurred. In summary, perineuriomas may arise in
      the intestine, most often as intramucosal lesions detected as colorectal polyps
      with distinctive histologic features including entrapment of colonic crypts.
      Distinguishing perineuriomas from other spindle cell neoplasms of the
      gastrointestinal tract can be facilitated by immunostaining for EMA and claudin
      1.

PMID- 15958850
TI  - Localized malignant mesothelioma.
AB  - Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of
      the serosal membranes with the microscopic appearance of diffuse malignant
      mesothelioma but without any evidence of diffuse spread. Little is known about
      their behavior. We report 23 new cases. The mean age at presentation was 63
      years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors
      were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic
      patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and
      sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of
      the tumor, 10 of 21 patients with follow-up data were alive without evidence of
      disease from 18 months to 11 years after diagnosis. Patients who died had
      developed local recurrences and metastases, but none had diffuse pleural spread.
      Localized malignant mesotheliomas should be separated from diffuse malignant
      mesotheliomas because of their localized presentation, quite different biologic
      behavior, and far better prognosis.

PMID- 15958851
TI  - Small glandular proliferations on needle biopsies: most common benign mimickers
      of prostatic adenocarcinoma sent in for expert second opinion.
AB  - The current study aimed to determine the incidence of various benign mimickers of
      prostatic adenocarcinoma most commonly encountered in a busy consultation
      practice. All prostate needle biopsies from the consult service of one of the
      authors were prospectively evaluated over a 7-month period. Only cases with foci
      where the contributor questioned malignancy and which upon expert review the
      entire case was determined to be benign were included in this study. A total of
      567 separate suspected atypical foci from 345 patients of a total of 4,046
      patients (8.5%) received in consultation were identified. Of these, 281 foci
      (49.5%) had immunohistochemical (IHC) studies performed by the outside
      institution, which included high molecular weight cytokeratin (HMWCK) (n = 280),
      alpha-methylacyl-CoA racemase (AMACR) (P504s) (n = 45), and p63 (n = 34). The
      most common mimicker was partial atrophy (203 of 567; 35.8%). Technically
      adequate IHC for basal cells was performed in 117 cases of partial atrophy with
      patchy or patchy/negative staining seen in 102 of 117 (87%), with the remaining
      13% of cases completely negative. A total of 15 of 19 (79%) cases of partial
      atrophy were positive with AMACR. Crowded benign glands, insufficiently crowded
      or numerous to warrant a diagnosis of adenosis, was the second most common
      mimicker (146 of 567; 25.7%). Crowded benign glands had patchy or patchy/negative
      IHC for basal cells in 66 of 81 (81%) cases with the remaining 19% of cases
      completely negative. A total of 7 of 11 (64%) cases of crowded glands were
      positive for AMACR. In the past, complete atrophy, adenosis, seminal vesicle, and
      granulomatous prostatitis were considered common mimickers of prostate cancer on
      prostatic needle biopsies. Our study shows that currently partial atrophy and
      crowded benign glands are the most common benign changes causing diagnostic
      difficulty and prompting consultation. Negative or patchy staining for basal
      cells and positive staining for AMACR may contribute to diagnostic difficulty in
      these entities.

PMID- 15958852
TI  - MUC1, MUC2, MUC4, and MUC5AC expression in salivary gland mucoepidermoid
      carcinoma: diagnostic and prognostic implications.
AB  - We determined whether immunostaining for mucins could provide a better
      characterization of salivary gland mucoepidermoid carcinoma (MEC). We
      investigated 63 MECs by immunohistochemistry for MUC1, MUC2, MUC4, and MUC5AC.
      Mucin expressing cell types and labeling patterns were recorded. The results were
      compared with microscopic grade, tumor-associated lymphoid infiltrate, mucin
      expression in surrounding salivary glands, clinical features, and outcome. MUC1
      and MUC4 labeled the apical membrane of glandular tumor cells and the entire
      membrane of intermediate, clear, and epidermoid tumor cells. MUC2 and MUC5AC were
      expressed in the cytoplasm of glandular, mucous, and intermediate tumor cells. In
      contrast to MUC1, MUC4 expression decreased with tumor grade (P < 0.01). Unlike
      MUC2, MUC5AC was expressed in more than 50% of high-grade tumors, including 2
      cases that were not stained with Alcian blue. MUC1 and MUC5AC were associated
      with tumor-associated lymphoid infiltrates (P < 0.05), but not with tumor
      associated lymphoid follicles. The proportions of tumors expressing mucins were
      71% for MUC1, 21% for MUC2, 79% for MUC4, and 68% for MUC5AC. MUC1 and MUC5AC
      were more frequently expressed in tumors than in surrounding glands (P < 0.0001).
      MUC1 expression correlated with shorter progression-free survival (P < 0.05). In
      conclusion, mucin expression in MEC differs from that in salivary glands.
      Intermediate cells express MUC1 and MUC4 all along their cell surface and MUC2
      and MUC5AC in their cytoplasm. Staining for MUC5AC in high-grade tumors can be
      helpful for distinguishing high-grade MEC from squamous cell carcinoma. While
      MUC4 is related to tumor differentiation, MUC1 expression indicates a worse
      prognosis.

PMID- 15958853
TI  - Differential expression of alpha-methylacyl coenzyme A racemase in
      adenocarcinomas of the small and large intestines.
AB  - Alpha-methylacyl coenzyme A racemase (AMACR), a novel immunomarker for prostatic
      adenocarcinoma, has recently been shown to be expressed in a number of
      malignancies including colorectal adenocarcinoma. In the current study, 59
      surgically resected primary small intestinal adenocarcinomas (34 ampullary and 25
      non-ampullary) were immunohistochemically examined for AMACR expression and
      compared with 66 colorectal adenocarcinomas (including 24 secondary tumors
      involving the small intestine by direct extension or metastasis). The results
      show that no AMACR immunoreactivity was detected in normal-appearing small and
      large intestinal mucosa. While 41 of 66 (62%) colorectal adenocarcinomas
      exhibited a variable degree of cytoplasmic staining, only 1 of 25 (4%) non
      ampullary and 2 of 34 (6%) ampullary small intestinal adenocarcinomas showed
      positive AMACR immunoreactivity (P < 0.0001). Interestingly, AMACR appeared to be
      less frequently expressed in mucinous or poorly differentiated colorectal
      adenocarcinomas when compared with non-mucinous or better-differentiated
      counterparts, suggesting an association with microsatellite instability status.
      These results extend our previous observations that small intestinal
      adenocarcinomas differ markedly from colorectal adenocarcinomas despite their
      morphologic similarity. The different AMACR expression patterns may not only
      provide an additional diagnostic tool in the distinction between adenocarcinomas
      of the small and large intestinal origins but may also shed light on further
      understanding of intestinal tumorigenesis.

PMID- 15958854
TI  - Patterns of allelic loss of synchronous adenocarcinomas of the lung.
AB  - Distinction of multiple primary lung carcinomas from intrapulmonary metastases
      using empiric clinical and histopathologic criteria can be difficult. Recent
      advances have provided several molecular markers that can be used for clonal
      analysis of separate tumor nodules and enhance tumor staging and subsequent
      treatment and prognosis. To address this issue, we performed a microdissection
      based allelotyping of 20 cases of histologically similar, pathologic stage T4
      adenocarcinomas (ADCs). Loss of heterozygosity (LOH) analysis included a panel of
      15 polymorphic microsatellite markers located on 1p, 3p, 5q, 9p, 9q, 10q, 17p,
      and 22q. The tumor size, visceral pleural and angiolymphatic invasion, lymph node
      status, outcome, and survival were assessed. Allelotypes of 60 cases of solitary
      primary non-small cell lung carcinomas (NSCLC) (stages I-II) were used to define
      the percentage of discordant LOH patterns within solitary primary lung carcinoma
      that would discriminate between survivors and nonsurvivors. These criteria were
      used in the analysis of pathologic stage T4 ADC. Two groups of stage T4 cases
      were created: molecularly homogenous (< or = 40% discordances) (14 cases, 70%),
      and molecularly heterogenous (>40% discordances) (6 cases, 30%). Molecularly
      homogenous tumors were more frequently associated with visceral pleural invasion
      (92% vs. 8%) (P = 0.018). Allelotype did not correlate with age, gender, tumor
      size, tumor differentiation, lymph node status, angiolymphatic invasion,
      survival, or outcome. Our study showed that discordant and concordant genotypic
      profiles exist in morphologically similar synchronous ADC of the lung.

PMID- 15958855
TI  - Histologic features of sinus histiocytosis with massive lymphadenopathy in
      patients with autoimmune lymphoproliferative syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder
      associated with defects in Fas-mediated apoptosis, characterized most often by
      childhood onset of lymphadenopathy, splenomegaly, hypergammaglobulinemia, and
      autoimmune phenomena. Children with sinus histiocytosis with massive
      lymphadenopathy (SHML) have a somewhat similar clinical phenotype in which
      prominent adenopathy also is associated with hypergammaglobulinemia, and
      autoimmune phenomena are reported in 10-15% of cases. We observed
      histopathological features of SHML in the lymph nodes of some of our ALPS
      patients, further suggesting an association between these two disorders. We,
      thus, reviewed the lymph nodes from 44 patients ALPS type Ia, all of whom were
      confirmed to have germline mutations in the TNFRSF6 gene encoding Fas (CD95/Apo
      1). Eighteen of 44 (41%) patients had a histiocytic proliferation resembling
      SHML. The affected patients included 15 males and 3 females ranging in age from
      11 months to 30 years at the time of the LN biopsy. The lymph nodes contained S
      100+ histiocytes with characteristic nuclear features of SHML, and showed
      evidence of emperipolesis in both hematoxylin and eosin (H and E) and
      immunostained sections. The extent of the histiocytic proliferation was variable,
      being confluent in 2 cases, multifocal in 13, and only evident as isolated SHML
      type histiocytes in 3. In lymph nodes without confluent SHML changes, increased
      numbers of CD3+CD4-CD8+ (double negative) alphabeta T-cells, also negative for
      CD45RO, a feature of ALPS, could be identified in the paracortex. Furthermore,
      because SHML shares many clinical features with ALPS, we sought evidence of ALPS
      in sporadic SHML. We attempted to sequence TNFRSF6 DNA from archived tissue of 14
      cases of Rosai-Dorfman disease. Full sequencing of the gene was successful in 4
      of the cases; no mutations were identified. Nevertheless, our observations
      suggest that histologic features of SHML are part of the pathologic spectrum of
      ALPS type Ia. It remains to be determined if some cases of apparently sporadic
      SHML may be associated with heritable defects in Fas-mediated apoptosis.

PMID- 15958856
TI  - Multinucleated epithelial giant cells in colorectal polyps: a potential mimic of
      viropathic and/or dysplastic changes.
AB  - Multinucleated epithelial giant cells (MEG) simulating viral cytopathic effect
      and/or dysplasia have been reported in the esophagus in association with
      inflammation, but the occurrence of similar cells in the colon has not been
      documented. Twenty-three colon specimens (22 biopsies and 1 partial colectomy)
      featuring MEG from 21 patients were evaluated for a variety of histologic
      features and correlated with clinical, endoscopic, and follow-up data. Patients
      included 9 males and 12 females (mean age, 64.9 years; range, 45-86 years).
      Eleven cases were obtained from 10 asymptomatic patients undergoing surveillance
      biopsies. Presenting symptoms in the remaining patients were dyspepsia, anemia,
      abdominal pain, and hematochezia. Over half (13 of 23) of the specimens were from
      descending and rectosigmoid colon, and almost all were visualized as polyps on
      endoscopy. Microscopically, all but 1 of the cases featured multiple MEG (range,
      6 to >50 cells per biopsy) in the base and mid crypt zones of inflamed polyps
      with serrated architecture. Immunohistochemical stains for CMV, HSV, adenovirus,
      EBV, and polyoma virus were negative and no viral particles were identified on
      ultrastructural examination. Nuclear staining for hMLH1 and hMSH2, markers of
      microsatellite instability, was similar in distribution to adjacent serrated
      crypts, but reduced staining intensity was noted in occasional multinucleated
      cells. Expression of Ki-67 and cleaved caspase 3 was consistent with a quiescent
      or low proliferative state. Clinical follow-up was available for 9 patients (mean
      duration, 22.7 months). One patient died of heart failure; all others were well
      at last follow-up. Bizarre MEG may occasionally be seen within the crypts of
      inflamed polyps with serrated architecture, raising concern for dysplasia or
      viral infection. Immunohistochemical and ultrastructural studies fail to
      establish a viral etiology, and follow-up does not indicate clinically aggressive
      disease. These changes appear to represent a nonspecific, possibly degenerative
      response to inflammation and injury, and should be distinguished from dysplasia.

PMID- 15958857
TI  - Gastrointestinal stromal tumors metastatic to the ovary: a report of five cases.
AB  - Five cases of gastrointestinal stromal tumor metastatic to the ovary are
      reported. The average patient age was 59 years (range, 44-81 years). The primary
      tumor was in the small bowel or its mesentery (4 cases) or stomach (1 case). The
      primary and metastatic tumors were discovered synchronously in 3 cases. In the
      other 2 cases, the ovarian tumors were discovered 18 months before a gastric
      tumor was identified and 27 years after a small bowel tumor had been resected.
      The ovarian tumors (three of which were bilateral) were usually solid, tan, and
      lobulated. Microscopically, three tumors had a pure spindle cell morphology, and
      two both spindle and epithelioid cell components. The diagnosis in all 5 cases
      was confirmed with positive c-kit (CD117) and negative desmin immunostaining.
      Variably positive immunoreactivity for either or both h-caldesmon and smooth
      muscle actin was seen in all 5 cases, and 3 cases were CD34-positive. Four
      patients died between 1 and 6.5 years (mean, 2.8 years) from the time of ovarian
      tumor diagnosis. The main differential diagnostic consideration was
      leiomyosarcoma; the most important features to help exclude this diagnosis were
      an absence of tumor in the uterus, low histologic grade, and a desmin-negative, c
      kit-positive immunophenotype. Other differential considerations, including
      endometrial stromal sarcoma and fibrosarcoma, are discussed. Most of the ovarian
      tumors in this series were initially diagnosed as tumors of other types, a
      misdiagnosis with significant therapeutic and prognostic implications because of
      the specific therapy now available for gastrointestinal stromal tumors.

PMID- 15958858
TI  - Primitive nonneural granular cell tumors of skin: clinicopathologic analysis of
      13 cases.
AB  - A rare subset of distinctive cutaneous nonneural granular cell tumors was
      described by LeBoit et al in 1991 and termed "primitive polypoid granular-cell
      tumor." Herein, we report our experience with 13 similar, distinctive nonneural
      granular cell tumors. Affected patients included 7 males and 6 females ranging in
      age from 5 to 83 years (mean, 25 years; median, 16 years). These cutaneous
      lesions involved the back (5 cases), neck, shoulder, thigh (2 cases each), chin,
      and elbow (1 case each). Clinically described as smooth, nontender cutaneous
      nodules, the tumors ranged in size from 0.2 to 2.8 cm (median, 0.8 cm) and were
      present from months to years before excision. Mitoses numbered from 1 to 6 per mm
      (median, 2). Eight of the lesions were polypoid, based in the papillary dermis
      with extension to the superficial dermis and associated with an epithelial
      collarette. Five of the lesions were situated deeper in the reticular dermis with
      limited extension into the subcutis but clinically were also nodular. All the
      tumors were well circumscribed and composed of spindled to ovoid cells with
      abundant granular, eosinophilic cytoplasm and vesicular nuclei with small
      prominent nucleoli. Immunohistochemistry revealed reactivity only for NKI-C3 (11
      of 12 cases), CD68 (7 of 11 cases), and NSE (5 of 10 cases); S-100 protein as
      well as other melanocytic, epithelial, and myoid markers were uniformly negative.
      All 13 of the lesions were locally excised and in the 8 cases with adequate
      follow-up ranging from 13 to 126 months (mean, 68 months; median, 41 months),
      none has recurred locally. However, one tumor (case no. 11) gave rise to a local
      lymph node metastasis 25 months after presentation, but the patient is currently
      disease-free 70 months after lymphadenectomy. These cutaneous granular tumors do
      not appear to be neural or Schwannian in nature, but their precise line of
      differentiation is unknown.

PMID- 15958859
TI  - Histopathology of the spleen in T-cell large granular lymphocyte leukemia and T
      cell prolymphocytic leukemia: a comparative review.
AB  - We review retrospectively the spleen histology in 8 patients with T-cell large
      granular lymphocyte (LGL) leukemia and 4 with T-cell prolymphocytic leukemia (T
      PLL) to identify characteristic patterns of involvement and to distinguish such
      patterns from those described in other low grade B- and T-cell malignancies.
      Moderate splenic enlargement with red pulp expansion due to lymphocytic
      infiltration was characteristic of LGL leukemia. Abnormal lymphocytes expressed
      cytotoxic granule proteins and were consistently CD45RO and CD5 negative in
      contrast to normal red pulp T cells. This infiltration respected anatomic
      boundaries with encroachment but no invasion of white pulp areas. Unlike in hairy
      cell leukemia, the main differential diagnosis for red pulp lymphocytosis, the
      white pulp was not only preserved in T-cell LGL leukemia but showed germinal
      center hyperplasia with expansion of the mantle zones. By comparison, T-PLL
      spleens showed marked red pulp lymphoid infiltration by medium-sized cells with
      irregular nuclei and prominent eosinophilic nucleoli. T-PLL lymphocytes, unlike
      LGLs, were more invasive, infiltrating the spleen capsule as well as white pulp
      areas. T-cell prolymphocytes did not express cytotoxic granule proteins or NK
      cell markers, were CD5+, CD45RO+ like normal spleen T cells, were CD2+, CD3+,
      CD45+, CD43+, TCRbeta+, but CD25-, CD30-, ALK-1-, TRAP-, DBA44-, and TdT-.
      Expression of CD4 and CD8 in these cells mirrored that of circulating T-PLL
      cells. These observations on the morphologic and immunohistochemical appearances
      of the spleen in T-cell LGL leukemia and T-PLL may aid diagnosis of these
      uncommon T-cell disorders, particularly T-cell LGL leukemia, where presentation
      may be cryptic and where unique pathognomonic features, are absent.

PMID- 15958860
TI  - Interobserver and intraobserver variability in the diagnosis of hydatidiform
      mole.
AB  - Surgical pathologists often encounter hydropic villi in products of conception at
      the first trimester and must determine whether the villi represent complete
      hydatidiform mole (CM), partial hydatidiform mole (PM), or hydropic abortion
      (HA). The distinction between these is important for determining the appropriate
      treatment of patients. This study assessed interobserver and intraobserver
      variability in the histologic diagnosis of hydatidiform mole among 5 placental
      pathologists. To evaluate interobserver variability, one representative slide
      from each of 50 mixed cases of PM, CM, and HA of the first trimester were
      circulated among 5 placental pathologists. All pathologists used the same
      histologic criteria by Szulman and Surti. For the second round, the same cases
      were submitted with DNA ploidy data. For the third round, the slides were recoded
      and distributed to assess intraobserver agreement. Kappa (kappa) value was
      calculated for the interobserver agreement in the first and second rounds. There
      was agreement among 4 or 5 pathologists for only 30 of 50 cases in the first
      round. There were problems in differentiating between PM and HA in most of the
      remaining 20 cases. The kappa values varied from poor (kappa = -0.104) to
      excellent (kappa = 0.761) in the first round. In the second round, there was
      agreement in 39 of 50 cases and the level of agreement remarkably increased,
      ranging from fair to good (kappa = 0.552) to excellent (kappa = 0.851). The
      number of discrepant cases, PM versus HA, was reduced to 4. In 7 cases, there
      were difficulties in distinguishing CM from HA. The intraobserver agreement
      ranged from 50% to 90%. Poor interobserver agreement was demonstrated when
      histology alone was used for diagnosis. Discordance was most frequently seen in
      PM versus HA and resulted from difficulty in evaluating trophoblastic
      hyperplasia. Polar trophoblastic growth seen in HA could also be observed in PM.
      The addition of ploidy data resulted in a significant improvement in concordance.
      Ploidy study is useful in equivocal cases. Significant interobserver and
      intraobserver variability was observed even among placental pathologists. New
      histologic criteria adaptable to differentiation of early lesions are needed.

PMID- 15958861
TI  - Peribronchiolar metaplasia: a common histologic lesion in diffuse lung disease
      and a rare cause of interstitial lung disease: clinicopathologic features of 15
      cases.
AB  - Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of
      peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely
      recognized, PBM has received little attention in the pathologic literature and is
      not known to have clinical significance. We identified 15 cases in which PBM was
      the only major histologic finding in surgical lung biopsies from patients with
      interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and
      pathologic findings. The mean age was 57 years (range, 44-74 years) with 13
      females and 2 males. One patient had been a welder with fume and asbestos
      exposure; another had pigeon exposure. Smoking history was available for 13
      patients: three current smokers, one cocaine user, two former smokers, and seven
      never smokers. Three patients had collagen vascular disease. One had elevated
      serum antinuclear antibody titers. Pulmonary function data were available for 10
      patients: one obstructive, five restrictive, two mixed obstructive and
      restrictive, and two normal. Computerized tomography in 7 patients showed mosaic
      attenuation in 3 patients and air trapping in 1 patient; no bronchiectasis,
      septal lines, or honeycombing were seen in any cases. All 11 patients with
      available follow-up are alive; 4 of them have experienced symptomatic improvement
      (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other
      interstitial lung diseases, which were assessed for this lesion: 59% of usual
      interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10
      of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity
      pneumonitis (9 of 18), and 11% of respiratory bronchiolitis (2 of 18). In
      summary, PBM is a common histologic finding in various interstitial lung
      disorders. It is rarely the sole major lung biopsy finding in patients presenting
      with interstitial lung disease (PBM-ILD). Patients are mostly older women, with
      mild symptoms and CT findings. Survival appears to be favorable.

PMID- 15958862
TI  - Uterine arterial embolization with tris-acryl gelatin microspheres: a
      histopathologic evaluation.
AB  - Uterine artery embolization (UAE) as an alternative to surgery for the treatment
      of uterine fibroids and adenomyosis uteri became increasingly popular. While the
      clinical success of this new treatment strategy is without doubt, there is still
      considerable uncertainty with respect to the morphologic changes induced by UAE.
      In this study, a total of 173 women were treated with UAE using tris-acryl
      gelatin microspheres (TGMS), a new particulate spherical embolic agent, for
      either symptomatic adenomyosis or leiomyoma. Surgical specimens of 8 women who
      underwent subsequent myomectomy or hysterectomy were evaluated by conventional
      histology and immunohistochemistry. TGMS were readily apparent in both macroscopy
      and routine histology. In patients with fibroids, TGMS accumulated in medium
      sized vessels in the direct tumor vicinity, a minor fraction of particles was
      detected in the outer half of the myometrium and within leiomyomata. In patients
      with adenomyosis, a random distribution of TGMS was noted throughout the outer
      half of the myometrium. Freshly infused particles occluded the respective
      arteries without a significant tissue reaction. In the course of time, a
      granulomatous foreign body reaction in the vicinity of particles occurred,
      eventually followed by complete vessel destruction. Leiomyoma treated with UAE
      showed either hyaline necrosis, coagulative necrosis, or no change at all. Foci
      of adenomyosis remained unaltered. In conclusion, after UAE with TGMS, particles
      were identified predominately but not exclusively at the periphery of fibroids.
      Pathologists must be aware of the morphologic changes induced by UAE in leiomyoma
      to avoid misinterpretation of induced tissue alterations as signs of malignant
      tumor growth.

PMID- 15958863
TI  - Minute foci of Gleason score 8-10 on prostatic needle biopsy: a morphologic
      analysis.
AB  - Prostatic needle biopsies showing high-grade cancer typically contain abundant
      tumor. However, the histologic features of a minute focus of high-grade cancer on
      biopsy have not been well studied. A total of 100 cases with a single minute
      focus (< or = 1 mm) of Gleason score (GS) 8-10 adenocarcinoma were identified
      from a large consultative service, systematically studied, and compared with the
      submitting institutions' provisional diagnoses. The mean size of the minute foci
      was 0.52 mm. A total of 29 cases were GS 8 with cribriform glands (n = 15),
      poorly formed glands (n = 6), fused glands (n = 3), or combinations of the three
      (n = 5). A total of 38 cases were GS 9, with: single cells and poorly formed
      glands (n = 20); extremely poorly formed glands/borderline pattern 4/5 (n = 4);
      combinations of single cells, sheets, or nests of cells mixed with glands that
      were either poorly formed, cribriform, or fused (n = 14). A total of 33 cases
      were GS 10, with single cells (n = 23), single cells with nests (n = 9), or
      single cells with sheets of cells (n = 1). A total of 69 foci were located
      adjacent to benign glands, while 31 were on the edge or at the end of the core.
      Perineural invasion was observed in only 1 case. A total of 72 cases showed
      moderate to abundant amphophilic cytoplasm. Frequent prominent nucleoli (n = 11),
      mitoses (n = 8), and apoptotic bodies (n = 11) were infrequently observed. Of 59
      cases with known provisional diagnoses, 46 were diagnosed as atypical (n = 37) or
      as cancer with GS < 8 (n = 9). Pathologists must be attuned to the complex and
      varied architectural patterns seen in low-volume, high-grade prostate cancer as
      its diagnosis has both important prognostic and therapeutic implications.

PMID- 15958864
TI  - Achlorhydria, parietal cell hyperplasia, and multiple gastric carcinoids: a new
      disorder.
AB  - We describe a 54-year-old woman who had multiple gastric carcinoid tumors arising
      in the setting of marked hypergastrinemia associated with a lack of acid
      production by hypertrophic parietal cells. The serum gastrin level was 1,400
      pg/mL, and investigation revealed no evidence for either of the recognized causes
      for hypergastrinemia-associated carcinoids, autoimmune gastritis, and Zollinger
      Ellision syndrome. Partial gastrectomy was performed. Pathologic examination
      showed multiple intramucosal and invasive carcinoid tumors of the body and fundus
      in a background of marked ECL cell hyperplasia. There were no gastric or duodenal
      ulcerations. One perigastric lymph node was metastatically involved. The oxyntic
      mucosa showed marked hyperplasia and hypertrophy of the parietal cells. Some of
      these cells were vacuolated, and many displayed protrusions of apical cytoplasm
      into dilated oxyntic glands filled with inspissated eosinophilic material.
      Similar findings have occurred in 1 other patient, strongly indicating that the
      clinicopathologic alterations in the 2 cases are not random but, on the contrary,
      represent a very rare disorder of gastric carcinoids associated with an intrinsic
      acid secretion abnormality of the parietal cells.

PMID- 15958865
TI  - Pulmonary sarcoidosis induced by interferon-alpha therapy.
AB  - Recombinant interferon-alpha (IFN-alpha) is being increasingly used in the
      treatment of chronic hepatitis C. It has been recently recognized that IFN-alpha
      can induce the development of sarcoidosis, presumably through its ability to
      stimulate the TH1 immune response. IFN-associated sarcoidosis is histologically
      similar to de novo sarcoidosis and is characterized by tightly compact
      epithelioid non-necrotizing granulomas. IFN-induced sarcoidosis may be
      unsuspected clinically, as the most common side effects of IFN-alpha simulate the
      symptoms of sarcoidosis. It is therefore important for pathologists to be aware
      of this association and encourage clinicians to carefully review the medication
      history in cases of pulmonary non-necrotizing granulomatous inflammation where
      there is a history of hepatitis C, as discontinuation of IFN-alpha can ameliorate
      the symptoms of sarcoidosis.

PMID- 15958866
TI  - Bong lung: regular smokers of cannabis show relatively distinctive histologic
      changes that predispose to pneumothorax.

PMID- 15958867
TI  - Tubulolobular carcinoma of the male breast.

PMID- 15958868
TI  - Intestinal spirochetosis.

PMID- 15958870
TI  - Addressing the global cardiovascular risk of hypertension, dyslipidemia, and
      insulin resistance in the southeastern United States.
AB  - An expanded occurrence of the metabolic syndrome in the U.S. population,
      especially in the Southeastern United States, has raised awareness of a need to
      revise our approach to the management of global cardiovascular risk factors while
      underscoring a need for more aggressive interventions and prevention measures. In
      defining the components of the metabolic syndrome and the interrelationship among
      obesity, hypertension, dyslipidemia, and insulin resistance, a basic framework
      for the medical management of this syndrome has been defined. In Part I of the
      consensus report prepared by the Workgroup on Medical Guidelines of the
      Consortium for Southeastern Hypertension Control (COSEHC), we analyze the
      components of the metabolic syndrome, discuss its pathophysiology, and recommend
      an approach to the quantitative analysis of the risk factors contributing to
      excess cardiovascular death in the region.

PMID- 15958871
TI  - Addressing the global cardiovascular risk of hypertension, dyslipidemia, diabetes
      mellitus, and the metabolic syndrome in the southeastern United States, part II:
      treatment recommendations for management of the global cardiovascular risk of
      hypertension, dyslipidemia, diabetes mellitus, and the metabolic syndrome.
AB  - An aggressive global approach to screening and to the management of the metabolic
      syndrome is recommended to slow the growth of the syndrome throughout the United
      States. Prevention should begin in childhood with healthy nutrition, daily
      physical activity, and annual measurement of weight, height, and blood pressure
      beginning at 3 years of age. Such screenings will identify cardiovascular risk
      factors early, allow the health care provider to define global cardiovascular
      risk with the COSEHC Cardiovascular Risk Assessment Tool, and allow treatment of
      each risk factor. Lifelong lifestyle modifications and pharmacologic therapy will
      be required in most patients. Antihypertensive therapy for these patients should
      begin with an angiotensin-converting enzyme inhibitor or an angiotensin receptor
      blocker unless a compelling indication for another drug is present. Metformin
      should be considered the first drug for glucose control in the patient with type
      2 diabetes. A statin should be used initially for hyperlipidemia unless
      contraindicated. Combinations of antihypertensive, antiglycemic, and lipid
      lowering agents will often be required.

PMID- 15958872
TI  - The 10-minute oral presentation: what should I focus on?
AB  - BACKGROUND: Little empirical evidence is available in the medical field defining
      the most important features of a scientific presentation. We sought to
      empirically identify what features of a scientific oral presentation experienced
      reviewers focus on when asked to identify the best features and areas to improve.
      METHODS: Observational study of 44 presenters at a scientific meeting over a 4
      year period. Reviewers observed presenters and identified the best features and
      made suggestions for improvement using an open-ended form. We developed a coding
      form based on three domains: content, slides, and presentation style. Two raters
      blinded to the presenter then coded the comments, and disagreement was resolved
      by concurrent review. RESULTS: Reviewers made at least one comment about content
      in 42 (95.5%) of the presentations, about slides in 38 (86.4%), and about
      presentation style in 42 (95.5%). The most frequently extracted comments on best
      features of presentations in the domain "content" were identifying a key concept
      (43.2% of presentations) and relevance (43.2%). Similarly, best features in the
      domain regarding "slides" were clarity (50.0% of presentations), graphics
      (27.3%), and readability of the text and font size (22.7%). Finally, best
      features in the domain regarding "presentation style" were clarity (59.1% of
      presentations), pace (52.3%), voice (47.7%), engaging with the audience (43.2%),
      addressing questions (34.1%), and eye contact (22.7%). Various other comments
      were noted to improve presentations. CONCLUSIONS: Important features during oral
      presentations relate to specific areas of content, clear slides, and a
      presentation style that was well paced, engaging, and clear. Nonverbal
      communication is important in oral presentations.

PMID- 15958873
TI  - Part I: use of echocardiography in the evaluation of patients with suspected
      cardioembolic stroke.
AB  - One-sixth of all ischemic strokes are a result of embolization from the heart.
      Echocardiography serves as the cornerstone in evaluating patients who may have
      had a cardioembolic stroke. This article is the first of a two-part review series
      focusing on the role of echocardiography in the diagnosis and treatment of
      cardioembolic stroke. Specifically, this section will focus on nonrheumatic
      atrial fibrillation as well as cardiovascular masses as potential embolic
      sources.

PMID- 15958874
TI  - Pheochromocytoma in a pregnant woman with a history of intracerebral aneurysms.
AB  - Pheochromocytoma in pregnancy is rare; if unrecognized, potentially fatal
      hypertensive crises may occur. We report a case of a 35-year-old woman with a
      history of two intracerebral aneurysms who presented at 26 weeks' gestation with
      tachycardia, hypertension, and pulmonary edema. Laboratory data revealed elevated
      24-hour urinary catecholamine and metanephrine levels, and abdominal sonography
      showed a 10-cm right adrenal mass. After stabilization with phenoxybenzamine and
      metoprolol, cesarean section was successfully performed at 36 weeks' gestation.
      Postpartum abdominal computed tomography scanning confirmed a 10-cm right adrenal
      mass. A benign pheochromocytoma was removed without incident. This case
      illustrates the importance of early diagnosis and management of pheochromocytoma
      in pregnancy and is also an example of the rare association of pheochromocytoma
      with intracerebral aneurysms.

PMID- 15958875
TI  - Troponin I elevation in a patient with acute severe bronchospasm.
AB  - Right ventricular strain is a source of troponin elevation in some patients with
      acute pulmonary embolism. Acute and/or severe obstructive airway disease could
      lead to a sudden increase in pulmonary arterial pressure and right ventricular
      afterload. We report a case of troponin I elevation in a 40-year-old woman who
      presented with acute severe bronchospasm and had a negative evaluation for
      coronary artery disease.

PMID- 15958876
TI  - Carcinoma of colon presenting as fever of unknown origin.
AB  - Fever of unknown origin (FUO) is defined as fever of more than 38.3 degrees C,
      the cause of which remains elusive after 1 week of intensive investigation. Most
      cases of FUO are restricted to infections, malignancies, and inflammatory
      diseases. FUO was previously reported as the presenting symptom of a few solid
      tumors such as lymphoma, renal cell carcinoma, and hepatocellular carcinoma.
      Colon carcinoma manifesting as FUO has been rarely reported. We describe three
      female patients who presented with classical FUO and microcytic anemia. As a
      control, we retrospectively evaluated 28 matched patients with carcinoma of colon
      and no fever. The evaluation included review of patient files, clinical and
      laboratory data, and pathologic specimens. In the three patients (mean age, 58
      years) who presented with FUO and had left-sided colon carcinoma and microcytic
      anemia, pathologic evaluation of the tumor tissues demonstrated a severe
      organized inflammatory process forming abscesses in the pericolic fat. The 28
      control matched patients showed no such histopathologic changes. In patients
      presenting with FUO, especially those who present with microcytic anemia, even
      with no bowel disturbances or elevated carcinoembryonic antigen levels,
      diagnostic workup should include a search for occult colorectal carcinoma. In our
      three cases, it appears that microabscesses in the pericolic fat are the cause of
      fever.

PMID- 15958877
TI  - Reperfusion-related polymorphic ventricular tachycardia as a possible mechanism
      of sudden death in patients with anomalous coronary arteries.
AB  - We describe a patient with anomalous origin of the left coronary artery in whom
      polymorphic ventricular tachycardia developed immediately after an episode of
      chest pain with ST segment elevation. This is the first report providing direct
      evidence that reperfusion arrhythmias may be the cause of sudden death in
      individuals with anomalous coronary arteries.

PMID- 15958880
TI  - A comparison of school performance and behaviors among working and nonworking
      high school students.
AB  - To evaluate the effect of after-school employment on Grade Point Average,
      absenteeism, school tardiness, extracurricular activities, and class-cutting, a
      cross-sectional anonymous questionnaire was completed by 7,506 high school
      students in May 2002. Working students did not report lower grades, higher
      absenteeism, or more school tardiness than their nonworking peers. However,
      students who worked were significantly more likely to cut classes and not take
      part in extracurricular activities than were students who were not employed.
      Factors associated with lower Grade Point Average among working students included
      working before 8:00 AM (adjusted odds ratio [AOR] = 1.73, 95% CI = 1.18-2.52),
      being injured at work (AOR = 1.47, 95% CI = 1.10-1.96), and feeling that the job
      was more important than school (AOR = 2.74, 95% CI = 2.08-3.60).

PMID- 15958881
TI  - Health and safety awareness for working teens: developing a successful, statewide
      program for educating teen workers.
AB  - Adolescents suffer higher rates of work-related injuries than do adults. A school
      based education program can provide young workers with information and skills
      that will reduce their risk. A successful program in Washington State, Health and
      Safety Awareness for Working Teens, adapted existing curricula to meet state
      needs. The curricula featured interactive exercises designed to engage students
      with a variety of learning styles. In-person trainings at teacher conferences
      proved the most effective way to disseminate the curricula across the state.
      Evaluations showed that student knowledge increased after exposure to the
      curricula and that teachers found the curricula to be useful and easy to use.

PMID- 15958882
TI  - Occupational risk among orchard workers: a descriptive study.
AB  - Orchard workers are exposed to an array of occupational health and safety hazards
      that result in injury, illness, and, in some cases, death. The purpose of this
      qualitative study was to identify and explore factors that contribute to
      occupational risks related to orchard work. Twenty-five Hispanic orchard workers
      were interviewed. They reported that the most common type of accident was falls,
      usually from a ladder; and the most common injuries were strains and sprains.
      Three broad categories of factors that contributed to the occurrence of such
      injuries were Knowledge, Attitudes and Behaviors; Work-Related Factors; and
      Factors External to Work.

PMID- 15958883
TI  - Development of educational and training materials on safety and health: targeting
      Hispanic workers in the construction industry.
AB  - The number of Hispanics in the construction work force continues to grow and
      their fatal and nonfatal occupational injuries are higher than those in any other
      ethnic group in the United States. Focusing on safety and health for this group
      may reduce injuries and promote safe workplaces. However, involving hard-to-reach
      workers is a difficult process because of language and cultural differences
      within ethnic groups. This article presents findings on effective design,
      development, and dissemination of safety and health educational materials
      targeted to Hispanic construction workers. How to utilize a linguistically and
      culturally sensitive approach is described. The author stresses the need for
      collaboration among researchers, unions, community development organizations, and
      advocacy groups in this effort.

PMID- 15958884
TI  - Factors influencing participation in worksite wellness programs among minority
      and underserved populations.
AB  - In the United States, employers and employees are increasingly paying a larger
      portion of the nation's healthcare bill. Preventive measures are being employed
      by businesses in an effort to contain the escalating costs of employee
      healthcare. The work site is an ideal setting for health promotion because 130
      million Americans are employed and spend one third of their time at work.
      However, unhealthy workers tend to be the least likely to participate in health
      promotion activities. Worksite Wellness Programs must be designed to engage
      segments of the work force with the greatest health needs. Culturally sensitive
      and appropriate programs must be developed to engage economically challenged
      minority and other underserved populations.

PMID- 15958885
TI  - The impact of work-related risk on nurses during the SARS outbreak in Hong Kong.
AB  - Severe acute respiratory syndrome (SARS) is a highly infectious disease, with
      high potential for transmission to close contacts, particularly among healthcare
      workers. This is the first systematic study investigating hospital nurses'
      physical and psychological health status and the kinds of healthcare used
      stratified by the level of contact with SARS patients-during the 2003 outbreak in
      Hong Kong. Nurses in moderate-risk areas appeared to have more stress symptoms
      than those working in high-risk areas. It is essential to design hospital support
      systems and occupational health policy to promote the psychological well-being of
      nurses during future outbreaks of emerging infections.

PMID- 15958886
TI  - Correction of adolescent idiopathic scoliosis using thoracic pedicle screw
      fixation versus hook constructs.
AB  - This retrospective study was undertaken to determine the effectiveness and cost
      of thoracic pedicle screws versus laminar and pedicle hooks in patients
      undergoing surgical correction of adolescent idiopathic scoliosis (AIS).
      Immediate preoperative and 6-week postoperative radiographs were examined in 25
      consecutive cases of children with AIS who were divided into two groups, those
      with thoracic pedicle screw constructs and those with thoracic hook constructs.
      Endpoints collected included radiographic measures, complications, surgical time,
      implant cost, and quality-of-life measures. Ten children underwent spinal fusion
      using thoracic pedicle screw fixation and 15 underwent thoracic constructs
      composed of hooks. Similar sex and age distribution were noted in both groups,
      and among the 20 girls and 5 boys the average age was 14.5. The mean preoperative
      Cobb angle was 53.5 degrees for the screw group and 52.5 degrees for the hook
      group. Correction averaged 70.2% for the screw group and 68.1% for the hook
      group. There were no significant differences between the two patient groups in
      terms of percentage of or absolute curve change after surgery. The apical
      vertebral translation, end vertebral tilt angle, and coronal balance did not
      differ significantly between the two patient groups. Comparison of operative time
      and quality of life revealed no significant differences. Screw constructs were
      significantly more expensive than hook constructs. The correction obtained from
      thoracic pedicle screw fixation is comparable to traditional hook constructs in
      AIS. Surgery using either construct effectively corrects AIS.

PMID- 15958887
TI  - The association between brace compliance and outcome for patients with idiopathic
      scoliosis.
AB  - This was a prospective study on the association of brace compliance and curve
      progression in idiopathic scoliosis. Compliance was measured electronically by
      embedding a temperature sensor and logger in the Wilmington scoliosis brace. To
      date there have been no studies that relate objective measures of compliance in a
      scoliosis brace to treatment outcomes. Thirty-four subjects with idiopathic
      scoliosis were monitored over the duration of their brace wear. Compliance data
      were downloaded and analyzed. The compliance rate for the patients whose curve
      progressed (>5 degrees) was 62%; the compliance rate for the patients who did not
      progress was 85% (P = 0.004). In the group that had high compliance (>90%), one
      of the nine subjects' curves progressed (11%). In the group with low compliance
      (<90%), 14 of the 25 subjects' curves progressed (56%, P = 0.0075). Results
      indicate that the more patients comply with brace treatment, the better their
      chances of a favorable outcome.

PMID- 15958888
TI  - Bone density accumulation is not affected by brace treatment of idiopathic
      scoliosis in adolescent girls.
AB  - Bracing for adolescent scoliosis has been postulated to cause permanent loss of
      bone mass and to predispose to adult osteoporosis. To determine whether brace use
      affects the rate of bone accretion with growth, the authors conducted a
      prospective study of 52 girls with adolescent idiopathic scoliosis. Dual-energy x
      ray absorptiometry (DEXA) showed a significant increase in spinal bone mineral
      density (BMD) over a 1-year period of brace wear. BMD correlated with measures of
      growth and pubertal status, but not average daily brace wear or severity of
      scoliosis. The annual rate of bone density accumulation was similar to reported
      normal values. The annual rate of change of volumetric bone density increased
      only slightly during the study period, suggesting that most of the change in BMD
      with time reflects growth in the dimensions of the spine. Brace treatment does
      not appear to inhibit bone density accumulation in girls with adolescent
      idiopathic scoliosis.

PMID- 15958889
TI  - Cervical kyphosis associated with anteroposterior dissociation and quadriparesis
      in Larsen's syndrome.
AB  - Neither the natural history nor the optimal treatment of cervical spine anomalies
      in Larsen's syndrome has been clearly defined. The authors describe two patients
      with Larsen's syndrome with cervical kyphosis, anteroposterior dissociation, and
      quadriparesis to show the variable clinical progression and offer a description
      of the authors' treatment. One patient has had continued neurologic and
      radiographic improvement with nonoperative treatment consisting of early
      traction. The other patient was treated with posterior fusion that failed to halt
      progressive kyphosis of the anterior vertebral bodies because of anteroposterior
      dissociation. He then was treated by resection of the posterior fusion, traction,
      and anterior and posterior decompression and fusion. Cervical kyphosis in
      patients with Larsen's syndrome is unpredictable, and both nonoperative and
      operative treatments have the potential to be successful. Anteroposterior
      dissociation of the cervical spine may be more common in Larsen's syndrome than
      recognized previously and may profoundly affect operative strategy and outcome.

PMID- 15958890
TI  - The surgical treatment of established congenital dislocation of the hip: results
      of surgery after planned delayed intervention following the appearance of the
      capital femoral ossific nucleus.
AB  - It has been proposed that the presence of the capital femoral ossific nucleus
      confers protection against ischemic injury or avascular necrosis (AVN) at the
      time of reduction of a congenitally dislocated hip. The current literature is
      contradictory. A prospective study was undertaken of the clinical and radiologic
      outcomes following closed or open reduction. Fifty hips were included in the
      study. These cases had presented late or had failed conservative treatment. In 28
      hips treatment was intentionally delayed until the appearance of the ossific
      nucleus (but not beyond 13 months) and in 22 the ossific nucleus was present at
      clinical presentation. Six hips reached the age of 13 months without an ossific
      nucleus appearing and progressed to treatment. The significant AVN rate (more
      than grade 1) was 7% for closed reduction and 14% for open. However, the amended
      rate if hips were excluded that had failed Pavlik harness treatment was 0.0% and
      9%, respectively (4% overall). Further surgical procedures were necessary in 57%
      of hips undergoing closed reduction and 41% after open, which compares favorably
      with other series. The authors conclude that the presence of the ossific nucleus
      is an important factor in the prevention of AVN, particularly after late closed
      reduction. Intentional delay in the timing of surgery does not condemn a hip to
      open surgery, but there is a comparable rate of secondary procedures becoming
      necessary, particularly after closed reduction. A simultaneous pelvic procedure
      may be appropriate after late closed reduction. The delayed strategy to await the
      appearance of the ossific nucleus for previously untreated dislocation allows a
      simple treatment algorithm to be employed that produces good clinical and
      radiologic outcomes.

PMID- 15958891
TI  - Increased chondrocyte apoptosis in growth plates from children with slipped
      capital femoral epiphysis.
AB  - Ultrastructural studies of slipped capital femoral epiphysis (SCFE) growth plates
      have shown diminished cellularity and marked distortion of the architecture in
      the proliferative and hypertrophic zones. Chondrocyte degeneration and death were
      noted at all levels of the hypertrophic and proliferative zones, suggesting an
      accelerated disturbance in the life-to-death cycle of the chondrocytes. The
      current study examines the mechanism responsible for the diminished cell number
      and whether increased programmed cell death (apoptosis) or necrosis was
      operative. Proximal femoral growth plates from patients with SCFE (three
      patients) were prepared and sectioned for histochemistry, in situ detection of
      apoptosis, and immunohistochemistry. The results showed that the diminished cell
      number is due to an abnormal frequency and distribution of chondrocytes
      undergoing apoptosis. Although it is unclear whether the increased apoptosis is
      occurring early or late in the disease, it is highly likely that it is directly
      linked to pathogenesis.

PMID- 15958892
TI  - Posterior sloping angle of the capital femoral physis: a predictor of
      bilaterality in slipped capital femoral epiphysis.
AB  - Different anatomic parameters were measured on radiographs of the healthy hip of
      47 patients with unilateral slipped capital femoral epiphysis (SCFE). Data were
      compared with those from 36 hips of 23 healthy adolescents matched in age,
      weight, and stature. During 5 years of follow-up, eight patients with unilateral
      SCFE developed slippage of the contralateral side. Patients with unilateral SCFE
      had a lower physis-diaphysis angle and a larger angle of physeal sloping in the
      AP view than controls, reflecting a more vertical orientation of the capital
      femoral physis. In the axial view, control patients had a mean value of the
      posterior sloping angle of the capital femoral physis of 5 degrees, compared with
      12 degrees in unilateral SCFE cases and 18 degrees in patients developing
      bilateral SCFE. The risk of developing bilateral disease can be predicted by
      measuring hip morphometric parameters, the most important factor being the
      posterior sloping of capital femoral physis in the axial view. Prophylactic
      pinning of the healthy contralateral side should be strongly recommend only in
      patients with unilateral SCFE showing an axial posterior sloping angle of the
      physis of over 12 degrees.

PMID- 15958893
TI  - Sugioka's Modified Hungria-Kramer intertrochanteric osteotomy in the treatment of
      severe slipped capital femoral epiphysis.
AB  - From May 1990 to November 1997, 24 cases of severe slipped capital femoral
      epiphysis were treated by an osteotomy that is a modification of the Hungria
      Kramer intertrochanteric osteotomy proposed by Sugioka (Hungria-Kramer-Sugioka
      osteotomy or HKS osteotomy). The degree of displacement as seen on the frog-leg
      lateral radiograph of the proximal femur was measured according to the deviation
      of the longitudinal axis of the epiphysis from the center line of the neck (Fish
      classification). All hips were considered as grade III and underwent HKS
      osteotomy. Sugioka's radiographic study (true AP view with the limb internally
      rotated until the patella is perpendicular to the x-ray beam, and lateral view
      with the hip in 90 degrees flexion and 45 degrees abduction) was performed before
      surgery to show that the real direction of the slip was posterior in relation to
      the neck. Clinical results were assessed according to Merle-D'Aubigne and Postel
      system modified by Charnley (hip score system that takes into consideration pain,
      gait, and joint motion). Roentgenographic results were considered good if none of
      the following was present: joint space decreased by more than 2 mm
      (chondrolysis), avascular necrosis of the femoral head, neck-shaft angle of less
      than 120 degrees, nonunion at the osteotomy site, and a epiphyseal plate still
      open. Follow-up varied from 31 to 120 months (average 65.1 months).

PMID- 15958894
TI  - Legg-perthes disease and heritable thrombophilia.
AB  - The etiology of Perthes' disease is unclear. Recent reports have suggested that
      inheritable thrombophilic disorders may be one of its pathogenetic causes. The
      G20210A prothrombin gene, factor V Leiden, and MTHFR C677T mutations have been
      identified as predisposing genetic factors for thrombosis. Ninety children
      diagnosed with Perthes' disease were studied. A family history of thrombosis and
      any other personal thromboembolic events were researched. PCR and endonuclease
      digestion were used to analyze factor V Leiden, prothrombin G20210A, and MTHFR
      C677T. Two hundred healthy donors were included as a control group. No patient
      had a family or personal history of early thrombotic events. Four children with
      Perthes' disease (4.4%) were heterozygous for G20210A polymorphism compared with
      controls (odds ratio: 2.07; 95% confidence interval: 0.40-8.46). No association
      between factor V Leiden and Perthes' disease was observed. Three patients (3.33%)
      were heterozygous for factor V Leiden (odds ratio: 1.36; 95% confidence interval:
      0.32-5.84). The prevalence of different genotypes of C677T MTHFR did not show
      statistical differences compared with controls. Eleven patients were homozygous
      for this polymorphism (odds ratio: 1.02; 95% confidence interval: 0.42-2.44).
      This study does not support the screening of this group of polymorphism in
      patients with Perthes' disease.

PMID- 15958895
TI  - The importance of surgeons' experience on intraobserver and interobserver
      reliability of classifications used for Perthes disease.
AB  - The objective of this study was to evaluate the percentage agreement and
      intraobserver and interobserver reliability for the Catterall, Salter-Thompson,
      Herring, and Stulberg classification systems, with special reference to the
      experience of surgeons. AP and frog-leg radiographs of 10 patients were evaluated
      by 18 reviewers with three levels of experience on two occasions. Each patient
      had three sets of radiographs of different stages of disease (initial stage,
      fragmentation phase, and healed phase). The interobserver percentage agreement
      rates were 28% for residents, 42% for senior surgeons, and 51% for pediatric
      orthopaedists for the Catterall classification in the initial stage; 63%, 46%,
      and 68% for the Salter-Thompson classification; 44%, 44%, and 61% for the Herring
      classification; and 34%, 37%, and 43% for the Stulberg classification at skeletal
      maturity. The Catterall, Herring, and Salter-Thompson classifications have a
      learning curve, and pediatric orthopaedists have better intra- and interobserver
      reliability. The Stulberg classification system when used at skeletal maturity
      consistently gave the best results for intraobserver and interobserver
      reliability for residents, senior surgeons, and pediatric orthopaedists. These
      results suggest that although the reliability of these classification systems
      improves with the experience of the observer, inter- and intraobserver error is
      generally high even among experienced pediatric orthopaedists.

PMID- 15958896
TI  - Cementless hip arthroplasty in juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in
      children. The hip is usually affected later, and its involvement is the most
      common cause of disability in JIA. Failure of medical and preventive treatment,
      significant joint destruction, or multiarticular involvement may necessitate
      total hip arthroplasty (THA) to restore good function. Related clinical trials
      show initially good THA results in most of the series, but long-term outcomes are
      uncertain due to a significant arthroplasty loosening rate in the initial years,
      particularly with cemented stems. The authors report the results of 62
      noncemented THAs in 34 children with JIA after an average follow-up of 6 years
      (range 3-13). Mean age at surgery was 18.3 years (range 11.8-31) and 14 of the 34
      children had active disease. Clinical results were good for hip function but less
      for global function. There were no infections. Two acetabular cups early in the
      series failed due to poor primary fixation and had to be revised. Survivorship
      analysis was performed with the Kaplan-Meier method. At 13 years, the survival
      rate was 100% for the femoral component and 90.1% for the acetabular component.

PMID- 15958897
TI  - Aneurysmal bone cysts of the pelvis in children: a multicenter study and
      literature review.
AB  - The authors analyzed a series of 15 pelvic aneurysmal bone cysts (9 boys and 6
      girls) in children and adolescents who were reviewed with an average follow-up of
      50.3 months. Pain and limp were the main symptoms. Four patients had no treatment
      after the open biopsy. Eleven patients were treated with curettage. Preoperative
      selective arterial embolization was performed in three cases before curettage.
      Two recurrences were noted after curettage; recurrences were treated successfully
      with further curettage. As a result, the authors recommend curettage; more
      aggressive operative intervention does not appear to be indicated. No major
      intraoperative vascular complications occurred. Spontaneous healing in a few
      cases (even in active or aggressive lesions) argues for clinical and radiologic
      observation after biopsy when possible. In case of a propitious evolution,
      observation must be continued and surgery might be avoided, but if the lesion
      increases, treatment must be proposed.

PMID- 15958898
TI  - Hip flexion contracture and lumbar spine lordosis in myelomeningocele.
AB  - The objective of this study was to assess the correlation between hip flexion
      contracture (HFC) and the sagittal alignment of the lumbar spine in ambulatory
      children with myelomeningocele. Ambulatory patients with myelomeningocele are
      generally free of scoliosis or kyphosis. Among them, some develop increased
      lumbar lordosis. It is postulated that HFC and increased lumbar lordosis may be
      correlated. Thirty-eight patients, with a mean age of 12.7 years, were evaluated.
      Standing lateral spine films were obtained and the lumbar lordosis was measured
      using the Cobb method. HFC was measured using the Thomas test. A statistically
      significant correlation was found between the lumbar curve and HFC. High values
      of lumbar Cobb angle (hyperlordosis) were correlated with high values of HFC.
      These results show a correlation between HFC and increased lumbar lordosis in
      ambulatory myelomeningocele patients.

PMID- 15958899
TI  - Kinematic and kinetic evaluation of the ankle joint before and after tendo
      achilles lengthening in patients with spastic diplegia.
AB  - Fourteen patients, at a mean age of 9.1 years (range 4.1-16.6 years), who had
      spastic diplegic cerebral palsy were evaluated before and after tendo Achilles
      lengthening (TAL). Follow-up (by gait analysis) after TAL ranged from 8 to 30
      months. A Vicon motion analysis system with six CCD cameras and two AMTI force
      plates provided three-dimensional measurements of joint motion and moments. The
      TAL procedure resulted in normal passive dorsiflexion of the ankle joint with the
      knee at 0 degrees of extension and 90 degrees of flexion, reduced plantarflexion
      during swing phase, and reduced premature plantarflexor moment. However, 10
      degrees greater than normal dorsiflexion of the ankle joint during mid-stance
      phase was indicative of a mild calcaneal gait pattern. The TAL procedure improved
      lower extremity function as documented by both kinematic and kinetic analysis in
      cerebral palsy.

PMID- 15958900
TI  - Cervical spine fracture-dislocation birth injury: prevention, recognition, and
      implications for the orthopaedic surgeon.
AB  - Spinal cord birth injury is rare, and orthopaedic surgeons infrequently encounter
      it. The injury is associated with hyperextension of the fetal head in utero and
      during delivery and with forceps-assisted breech vaginal deliveries. These
      cervical spinal cord injures may be complete or partial. They most commonly occur
      in the absence of bony injury, which can lead to diagnostic difficulties.
      Ultrasound and MRI studies are valuable diagnostic tools for identifying spinal
      cord injury in cases of hypotonic newborns with difficult deliveries. The authors
      report an unusual case of spinal cord birth injury with frank cervical fracture
      dislocation following a difficult footling breech vaginal delivery. Early
      recognition of hyperextension of the fetal head in utero and planned cesarean
      section are important prevention methods. While this type of injury is rare, the
      pediatric orthopedic surgeon must understand its nature and severity to
      facilitate timely treatment.

PMID- 15958901
TI  - Base of distal phalanx fracture in children: a mallet finger mimic.
AB  - The authors present a series of seven juxtaepiphyseal fractures at the base of
      the distal phalanx of the finger. Prior to closure of the epiphysis, the fracture
      line is usually through the growth plate (Salter-Harris type I or II) or 1 to 2
      mm distal to the plate. Clinically the injury looks like a mallet finger, but the
      pathoanatomy is not that of the classic mallet. All seven of these fractures were
      treated by closed reduction, six fractures were fixed by a Kirschner wire, and
      one was held by splinting only. All healed without complications.

PMID- 15958902
TI  - Cast immobilization versus percutaneous pin fixation of displaced distal radius
      fractures in children: a prospective, randomized study.
AB  - Thirty-four patients were enrolled in a prospective randomized study comparing
      cast immobilization alone versus percutaneous pin fixation following closed
      reduction of distal radial metaphyseal fractures. Patients older than 10 years of
      age with greater than 30 degrees of dorsal angulation or with complete fracture
      displacement were eligible for enrollment. Average follow-up was 10.5 weeks. All
      fractures healed uneventfully without deformity, growth arrest, or functional
      limitations. Overall complication rates were similar between groups. Thirty-nine
      percent of patients treated with casting had subsequent loss of reduction
      requiring remanipulation; there were no cases of loss of reduction in patients
      treated with pin fixation. Thirty-eight percent of patients treated with pin
      fixation had pin-related complications; all resolved following pin removal
      without long-term sequelae. Cost analysis showed no significant difference in
      treatment charges between groups. Treating surgeons should be aware of the
      potential short-term complications of each treatment method and adjust their
      postoperative care appropriately.

PMID- 15958903
TI  - Minimalistic approach to treating wrist torus fractures.
AB  - Thirty-three patients with unilateral wrist torus fractures were reviewed
      retrospectively. Patients were all treated with a removable plaster-of-Paris
      volar forearm splint and a symptom-based splinting protocol. This protocol
      emphasized the parents and patients deciding when to wean from the splint as
      their symptoms improved. Patients were followed about 4 weeks after fracture, and
      initial and follow-up radiographs were compared for any changes in fracture
      angulation. All of the fractures healed without significant clinical change in
      angulation or complications. The authors propose the following treatment
      protocol: radiographic diagnosis and application of the removable splint in the
      emergency department, and one orthopaedic office/clinic visit to confirm the
      diagnosis and provide splinting instructions. The elimination of the additional
      orthopaedic visit for repeat radiographs and cast removal reduces the family's
      time lost from school and work and the physician's time and costs.

PMID- 15958904
TI  - Open reduction and annular ligament reconstruction with fascia of the forearm in
      chronic monteggia lesions in children.
AB  - Fifteen children with chronic Monteggia lesions were treated with open reduction,
      annular ligament reconstruction with fascia of the forearm, and ulnar osteotomy.
      Mean age was 8 years 3 months (range 3-16 years). The chronicity of missed
      Monteggia was from 6 weeks to 2 years (mean 12 weeks). All patients were
      classified as Bado type I, except one with Bado type III. Mean follow-up was 4
      years 3 months after surgery. There was a loss of pronation in six cases with the
      mean of 16 degrees. However, only four cases had rotational loss; the others had
      a mean rotational arch increase of 5 degrees. The flexion arches improved in all
      patients, with a mean of 27.7 degrees. The functional result was excellent in 11
      patients, good in 3 patients, and poor in 1 patient. This one-incision approach
      is safe in treating chronic Monteggia lesions in children.

PMID- 15958905
TI  - Closed treatment of displaced diaphyseal both-bone forearm fractures in older
      children and adolescents.
AB  - The management of adolescent radius and ulna diaphyseal fractures is
      controversial. The purpose of this study was to address the residual deformity
      and functional outcome following closed treatment of these fractures. Twenty-five
      older children and adolescents (mean age 13.3 years, range 8.8-15.5) with
      displaced diaphyseal both-bone forearm fractures underwent closed treatment and
      were followed for a mean of 49.6 weeks. All fractures united. On the final AP
      radiograph, the mean angulation was 9 degrees (range 0-18 degrees) for the radius
      and 8 degrees (0-20 degrees) for the ulna. All patients achieved full elbow and
      wrist range of motion. Loss of forearm supination and pronation averaged 4
      degrees (range 0 to 20 degrees) and 6.8 degrees (0 to 40 degrees), respectively.
      Closed reduction and casting of displaced both-bone diaphyseal forearm fractures,
      despite the residual angulation, results in satisfactory functional outcome and
      should remain a viable treatment option in the management of this injury.

PMID- 15958906
TI  - Nonoperative management of pediatric type I open fractures.
AB  - The purpose of this study was to examine the results of pediatric patients with
      type I open fractures managed nonoperatively. A retrospective chart review of all
      type I open fractures managed nonoperatively from 1998 to 2003 was performed.
      Forty patients were followed until healing of the fracture clinically and
      radiologically. One deep infection occurred in this series, producing an overall
      infection rate of 2.5%. This compares favorably with the literature's infection
      rate of 1.9% in pediatric type I open fractures treated operatively. There was a
      0% infection rate in the 32 upper-extremity type I open fractures and a 0%
      infection rate in the 23 patients under age 12. These results suggest that
      nonoperative management of pediatric type I open fractures is safe and effective,
      especially in children under age 12 with upper-extremity fractures.

PMID- 15958907
TI  - Outcome of physeal and epiphyseal injuries of the distal tibia with intra
      articular involvement.
AB  - The authors reviewed 83 physeal and epiphyseal injuries of the distal tibia with
      intra-articular involvement. The children, aged 11 to 14 years, were treated in
      the authors' department during 1987 to 1999. Treatment was nonoperative for
      72.25% (60/83) and surgical for 27.75% (23/83) according to specific indications.
      This gives the basis for a classification of these injuries. The main purpose of
      the study was to investigate the long-term results of these injuries according to
      a radiologic classification. The parameters considered were the patient's age,
      the mechanism of injury, and the possibility of growth deformities or functional
      disorders. They were studied relative to the long-term results, with a follow-up
      of 2 to 13 years. Regardless of treatment, varus deformity, ranging from 10 to 15
      degrees in relation to the normal opposite leg, occurred in four cases. In only
      one case was there painful limitation of ankle joint movement; in two other
      children an overgrowth of the medial malleolus was detected, with no functional
      impairment.

PMID- 15958908
TI  - Recurrence rates of burn contracture ankle equinus and other foot deformities in
      children treated with Ilizarov fixation.
AB  - The purpose of this study was to determine recurrence rates of pediatric foot and
      ankle burn deformities treated with the Ilizarov method. A total of 19 patients
      with 29 foot and ankle deformities were studied. The most common deformity
      treated was equinus (23). Rocker-bottom and cavus foot deformities were each
      treated three times. The average age of the patient at the time of the burn
      injury was 3.2 years, and the average age at the time of fixation was 9.4 years.
      Equinus contractures averaged -34 degrees (34 degrees of plantarflexion) before
      surgery and +7 degrees (7 degrees of dorsiflexion) after treatment with the
      Ilizarov fixator. The recurrence rate for all 29 ankles and feet was 69% (20/29).
      The recurrence rate for equinus contractures was 74% (17/23). The average time to
      recurrence was 17.3 months. Only short-term follow-up was available on four of
      the six feet and ankles that did not recur. Deformity correction in burned feet
      and ankles is difficult to obtain by any means. The authors recommend using the
      Ilizarov method to obtain correction of moderate to severe foot and ankle
      deformities in pediatric burn patients, but the correction obtained is not stable
      and deformity will likely recur. Parents and patients should anticipate
      adjunctive nonoperative and operative procedures to keep their feet plantigrade
      as they grow. In young children, the possibility of having additional surgeries,
      including repeat Ilizarov procedures, should be discussed. Even older children
      should expect additional surgeries to prevent recurrent deformities.

PMID- 15958909
TI  - Effect of postoperative early ankle motion exercise using hinged ankle-foot
      orthoses in clubfoot.
AB  - The authors proposed early application of hinged ankle-foot orthoses for
      improving postoperative range of ankle motion after the complete subtalar release
      operation for clubfoot. Forty-eight patients (74 feet) with clubfoot were divided
      into two groups: group A patients (20 feet) were immobilized in plaster casts for
      6 weeks after surgery, followed by non-hinged ankle-foot orthoses, and group B
      patients (54 feet) were immobilized in plaster casts for 4 weeks after surgery,
      followed by hinged ankle-foot orthoses. The range of ankle plantarflexion in
      group B showed a significant improvement compared with group A at 3 months and 1,
      2, and 3 years after surgery. There was no statistical difference between the
      groups in the range of dorsiflexion except at 3 months of follow-up. The
      postoperative talo-calcaneal index was well maintained in both groups. Early
      range-of-motion exercises using the hinged ankle-foot orthoses achieved good
      ankle function, especially in plantarflexion, with no loss of radiologic
      correction.

PMID- 15958910
TI  - Patient-based outcomes following clubfoot surgery: a 16-year follow-up study.
AB  - The ongoing controversy regarding the appropriate treatment of clubfoot has
      resulted in much variability in practice patterns, making the assessment of long
      term outcomes a difficult one. Recently, new patient-based measures of outcomes
      have allowed for improved methods of assessing health outcomes in children. The
      purpose of this study was to follow up on a cohort of adolescents who underwent
      surgical repair at the authors' institution. Traditional (radiographs) and
      patient-based measures were obtained from 24 patients. The Child Health
      Questionnaire showed that the quality of life of these patients was relatively
      high after surgery, and these scores were comparable to those of age-matched
      young athletes with healthy feet. The disease-specific instrument, which was also
      administered, showed similar results. The role of radiographic measures was
      limited, as they did not reflect patient-based outcomes after clubfoot surgery.
      Both generic and disease-specific measures should be used as primary endpoints in
      evaluating treatment results in this area.

PMID- 15958911
TI  - Multiplier method for prediction of adult height in patients with achondroplasia.
AB  - To date, the only way to predict adult height in achondroplastic dwarves has been
      to consult a growth chart. The purpose of this study was to ascertain whether the
      multiplier method of predicting adult height at skeletal maturity in healthy
      persons can be applied to persons with achondroplasia. Previous studies have
      shown that the multiplier method can be applied to lower limb length, upper limb
      length, total height, foot length, and foot height. It is therefore reasonable to
      suggest that the growth pattern for total height in achondroplastic dwarves might
      also be characterized by a multiplier. Total height multipliers for
      achondroplastic dwarves ("achondroplasia height multipliers") were calculated
      from two separate databases by dividing height at maturity by height at each
      respective age for both genders. Little variability was found among multipliers
      for each age and among multipliers calculated from different databases. Upper
      torso (sitting height) multipliers and lower limb multipliers were also derived
      for achondroplastic dwarves. Lower limb and total height growth rates were slower
      in achondroplastic dwarves compared with healthy persons. However, sitting height
      multipliers for achondroplastic dwarves were closely related to sitting height
      multipliers for healthy persons. Because these findings showed that the
      multiplier values were independent of population and percentile, the multiplier
      method may be a valid method for quickly predicting height at any age for
      achondroplastic dwarves.

PMID- 15958912
TI  - Outcomes of lengthening short lower-extremity amputation stumps with planar
      fixators.
AB  - Patients with short lower-extremity amputation stumps exhibit poor prosthetic fit
      and inefficient gait. Often they are fit at the next-higher prosthetic level,
      increasing energy consumption. This study aimed to characterize the risk/benefit
      ratio of stump lengthening with planar external fixators. All patients lengthened
      for functionally short amputation stumps were reviewed. Outcome measures included
      changes in prosthetic use, soft tissue problems, qualitative gait analysis, and
      surgical complications. Patients averaged 15.1 years of age at surgery, with 4.1
      years of follow-up. The average lengthening index was 9.2 mm/mo. Femoral
      lengthenings obtained more length (8.7 vs. 6.9 cm). After treatment, prosthetic
      skin-related complications decreased and qualitative gait parameters improved.
      Most (85%) wore a standard prosthesis for their amputation level after surgery,
      whereas none could before. There were 1.4 complications per patient, all
      successfully surgically treated. Lengthening is time-consuming and associated
      with frequent complications but results in improved gait and energy consumption.

PMID- 15958913
TI  - Diaphyseal derotational osteotomy with intramedullary fixation for correction of
      excessive femoral anteversion in children.
AB  - Nearly all children with femoral anteversion spontaneously remodel by age 8.
      Femoral derotational osteotomies are performed in older children with persistent
      excessive femoral anteversion when children or adolescents are limited in
      activities of daily living or sports. Procedures for correction of the
      anteversion vary, and no one procedure has been shown to be superior. Since 1997
      the authors have corrected idiopathic excessive femoral anteversion thorough a
      diaphyseal osteotomy with fixation using a rigid intramedullary pediatric femoral
      nail. The purpose of this study was to describe the technique and results of this
      new technique. A retrospective study was conducted of all femoral derotational
      osteotomies performed with a pediatric femoral nail in 13 consecutive patients
      and 21 affected limbs. All patients complained preoperatively of frequent
      tripping during sports and activities of daily living. The mean preoperative
      rotation included internal rotation of 77 degrees and external rotation of 15
      degrees. Standing AP radiographs of all patients were obtained at final follow
      up. All patients were evaluated clinically and radiographically at a minimum of 1
      year after surgery. All patients noted improvement in the ability to participate
      in activities without tripping. No patient limped at final follow-up. No
      intraoperative or postoperative complications occurred. Healing of the osteotomy
      was present at a mean of 6 weeks. All osteotomies healed in anatomic alignment.
      Mean final hip rotation included internal rotation of 40 degrees and external
      rotation of 57 degrees. No patient had substantial changes of valgus or femoral
      neck narrowing at final follow-up. Femoral derotational osteotomy with fixation
      using a small-diameter rigid intramedullary nail placed through the lateral
      aspect of the greater trochanter is a safe, accurate, and effective method of
      correcting excessive femoral anteversion in symptomatic children.

PMID- 15958914
TI  - Duchenne muscular dystrophy and steroids: pharmacologic treatment in the absence
      of effective gene therapy.

PMID- 15958915
TI  - Metal removal in asymptomatic children and adolescents.

PMID- 15958917
TI  - Continued use of an outdated method of osteotomy fixation for the proximal femur.

PMID- 15958918
TI  - Advocate the use of this anterior spinal fusion.

PMID- 15958920
TI  - Use of different types of operating tables when fixing slipped capital femoral
      epiphyses (SCFE) by a percutaneous technique.

PMID- 15958922
TI  - Who goes first?

PMID- 15958923
TI  - Local health department applies incident management system for successful mass
      influenza clinics.
AB  - Faced with a national influenza vaccine shortage in fall 2004, the Anne Arundel
      County (Maryland) Department of Health was forced to alter plans for influenza
      vaccine distribution to reach County residents most at risk. While approximately
      37,000 doses of vaccine had been ordered and were to be administered through 17
      large flu clinics, only 8,000 doses of flu vaccine were now available for
      distribution. This year's vaccine shortage provided an opportunity to test the
      Department's capacity to mobilize mass clinics in the event of a natural
      emergency or bioterrorism. Implementation of Incident Management System and
      utilization of partnerships with County and State agencies and media proved that
      the community's readiness relies on the quality and training of the local public
      health infrastructure.

PMID- 15958924
TI  - Multifaceted syndromic surveillance in a public health department using the early
      aberration reporting system.
AB  - Local health departments concerned with early detection of potential terrorist
      threats are beginning to explore novel approaches to syndromic surveillance.
      Using the Early Aberration Reporting System (EARS) developed by the Centers for
      Disease Control and Prevention, a metropolitan health department in Tennessee and
      five community partners have agreed to exchange data in order to implement a
      multifaceted syndromic surveillance system for early detection of a biological
      attack. This article describes how we used EARS as the foundation for
      implementing a surveillance system that encompasses a rich variety of data
      sources. We address technical requirements for operating EARS, recommend staffing
      and training prerequisites, describe the involvement of our data partners, and
      provide details related to data transfer and analysis, review, and response
      protocol. Other health departments may find this information useful as a general
      model for implementing EARS-based syndromic surveillance systems in their own
      jurisdictions.

PMID- 15958925
TI  - Optimizing a District of Columbia Strategic National Stockpile dispensing center.
AB  - On October 4, 2003, the District of Columbia Department of Health (DOH) held a
      Strategic National Stockpile (SNS) exercise designed to test its plan for
      operating mass dispensing centers during a bioterrorist attack or other
      emergency. The main goals of the exercise were to maximize the throughput of the
      dispensing plan and improve dispensing procedures. These goals are important for
      quantifying the resources (eg, numbers and types of staff) necessary to respond
      to different types and sizes of events, as well as for minimizing the potential
      for errors or confusion in dispensing medications. We set up the dispensing
      center according to the District's SNS plan and recruited volunteers to role-play
      potentially exposed residents. During the exercise, we collected detailed data on
      the service times for each step in the dispensing process. We also collected
      observations from exercise participants and observers. We found that the DOH
      dispensing center could achieve a throughput of 2.5 persons per minute. Using
      computer modeling, we recommended changes to the dispensing plan that would
      enable it to achieve a higher throughput of four to five persons per minute.
      Other recommendations addressed improvements to dispensing plans and procedures.

PMID- 15958926
TI  - Linkages of acute care and EMS to state and local public health programs:
      application to public health programs.
AB  - Response to terrorism and mass casualty incidents has become a focal point for
      many public service agencies. Public health agencies and the emergency response
      community must work together to effectively and efficiently respond to any future
      incidents. Historically, collaboration has been a challenge since these agencies
      have functioned independently from one another, maintaining separate
      infrastructures that are not adequately interoperable. This article will
      summarize the consensus achieved during a meeting of multidisciplinary
      stakeholders held to discuss linkages between acute care, emergency medical
      services, and public health. The relevancy of these findings to public health, as
      well as the benefits from development of an interoperable infrastructure to
      public health, will be opined.

PMID- 15958927
TI  - Why just prepare for emergencies when full use is possible?
AB  - Emergency preparedness, fits within the larger context of governmental public
      health preparedness. Full use of current, appropriations for learning management,
      education, and training systems designed for emergency preparedness can prepare
      and retain the current workforce to promote health and prevent disease, while
      recruiting the next generation to the governmental public health workforce.

PMID- 15958928
TI  - A case exercise: outbreak investigation at a Vermont community hospital.
AB  - Fifteen employees became ill with headaches, nausea, and vomiting due to chemical
      poisoning at a Vermont community hospital on January 3, 1980. An epidemiologic
      and environmental investigation was conducted to determine the source of the
      illness. The investigation discovered that the vapors of a chemical called
      xylene, which had previously been disposed of down a drain, were drawn back
      through the sewer into specific work areas. These vapors were determined to be
      the most likely cause of the illnesses. This outbreak investigation was used to
      create an exercise that has been used in a variety of teaching settings.

PMID- 15958929
TI  - A case exercise in public health preparedness: a community outbreak of influenza
      like illness.
AB  - Public health emergency preparedness has been a priority of local and state
      health departments as well as other community partners for several years. This
      article provides a tool for teaching a wide audience of learners the essential
      steps in training for a disease outbreak. This teaching case involves an
      investigation of and the community's response to an outbreak of influenza-like
      illness. Students learn skills in surveillance and hypothesis generation with
      regard to the outbreak. During the exercise, the learners are divided into teams
      to develop a response plan. The teams include Command and Coordination, Public
      Communication, Hospitals and Health Care Providers, Emergency Management and
      Public Safety, and Public Health. While the teams are developing their response
      plan, the etiology of the outbreak becomes clear. Once the etiology is known,
      each of the teams then develops an action plan to minimize the impact of the
      outbreak.

PMID- 15958930
TI  - A public health approach to reducing morbidity and mortality among homeless
      people in Boston.
AB  - Urban homeless populations suffer disproportionately high rates of premature
      death. In response to a wave of highly publicized deaths on the streets of Boston
      during the winter of 1998-1999, the Massachusetts Department of Public Health
      (MDPH) convened a task force to investigate these deaths and implement an
      integrated response to this public health crisis. Comprised of a broad coalition
      of public and private agencies as well as homeless persons and advocacy groups,
      the MDPH Task Force reviewed the circumstances surrounding the 13 deaths,
      monitored subsequent deaths among homeless persons in Boston, and implemented a
      comprehensive plan to address critical needs and prevent further deaths. Contrary
      to the task force's initial assumption, the 13 decedents had multiple recent
      contacts with the medical, psychiatric, and substance abuse systems. In response
      to this finding, the MDPH Task Force sought to improve continuity of care and
      prevent future deaths among Boston's street population. Coordination of needed
      services was achieved through the creation of new, and often unconventional,
      partnerships. This case study exemplifies a public health practice response to
      the vexing health care challenges confronting homeless people who must struggle
      to survive on the streets and in shelters.

PMID- 15958931
TI  - Local public health performance measurement: implementation strategies and
      lessons learned from aligning program evaluation indicators with the 10 essential
      public health services.
AB  - This case study summarizes the development and implementation of the evaluation
      framework, preliminary data results, and lessons learned for overcoming barriers
      and challenges. The framework development was based on best practices in
      evaluation and the Public Health Essential Services. Results were as follows: (1)
      implemented a department-wide framework for program evaluation; (2) developed and
      implemented 34 program evaluation plans; (3) collected data on 52 indicators
      across 492 measurable objectives; and (4) identified challenges and
      recommendations to improve evaluation processes. Although the importance of
      program evaluation is recognized in public health, program evaluation models do
      not take into account the variety of goals inherent in the diversity of public
      health programming. The case study presented provides guidance and lessons
      learned for the evaluation of public health practice in local governments.

PMID- 15958932
TI  - Hispanic health status in Orange County, Florida.
AB  - PURPOSE: To assess the health status of the Hispanic population of Orange County,
      Florida. METHODS: The methodology utilized secondary data for 66 ethnically
      identified indicators in a comparative framework applied for a 5-year period
      (1997-2001). FINDINGS: Orange County Hispanics are younger with lower per capita
      income than their Florida peers, less likely to be White, and much more likely to
      be of Puerto Rican origin. Relative to the Hispanic populations in the selected
      peer counties and statewide, Orange County Hispanics have higher age-adjusted
      death rates for a majority of disease categories and conditions, such as breast,
      lung, and prostate cancers; chronic liver disease and cirrhosis; diabetes
      mellitus; pneumonia and influenza; stroke; acquired immunodeficiency syndrome;
      motor vehicle accidents; and infant, neonatal, and child mortality. Orange County
      Hispanics did better in comparison to Orange non-Hispanics, with lower age
      adjusted death rates for major causes of death such as heart disease, cancer, and
      stroke. However, for many indicators, the 5-year trends for Orange County
      Hispanics are moving in an unfavorable direction in contrast to the trends for
      non-Hispanics, which are either stable or improving. CONCLUSION: Comparative
      assessments of Hispanic populations using secondary data enable the development
      of a comprehensive health status profile. However, this approach is currently
      constrained by the limited number of ethnically identified indicators and,
      especially for Hispanics, problems in the accuracy and consistency of the
      assignment to racial categories and subsequent reporting.

PMID- 15958933
TI  - Who supports tobacco excise taxes? Factors associated with towns' and
      individuals' support in Massachusetts.
AB  - OBJECTIVES: The authors examined factors related to public support for cigarette
      taxes: smoking behavior, attitudes about other tobacco control policies, and
      sociodemographic factors. METHODS: The authors regressed referendum voting
      outcomes on sociodemographic characteristics of Massachusetts' 351 towns.
      Logistic regressions on the surveys of Massachusetts adults (N = 14,000+) showed
      support for hypothetical tax increases to be related to respondents' smoking
      status, support for other tobacco control policies, and sociodemographic
      characteristics. RESULTS: Average educational attainment, probably acting as a
      proxy for nonsmoking prevalence, strongly predicted town-level support for
      Massachusetts' 1992 cigarette tax referendum. Survey respondents' support for
      hypothetical further increases was strongest if tax proceeds were earmarked for
      tobacco control or health purposes and if the individual was a nonsmoker and
      favored other tobacco control policies. For an earmarked tax, support was
      stronger among younger persons, females, persons with higher education,
      racial/ethnic minorities, and smokers with children. CONCLUSIONS: The high
      nationwide proportion of nonsmokers means that tobacco tax proposals can obtain
      strong voter support, but only if tax revenues are clearly earmarked for tobacco
      control and similar uses. Individual- and town-level characteristics can identify
      likely concentrations of support. Because attitudes toward tobacco control are
      only partly linked to smoking status, education campaigns may make a difference.

PMID- 15958934
TI  - Disparity in the use of smoking cessation pharmacotherapy among Medicaid and
      general population smokers.
AB  - BACKGROUND: The prevalence of smoking remains higher among the Medicaid
      population compared with the general population. To reduce this disparity, the
      majority of state Medicaid programs now provide coverage for smoking cessation
      pharmacotherapy. The objectives of this study were to (1) assess awareness of
      this benefit among Medicaid smokers and (2) compare the use of pharmacotherapy
      among a sample of Medicaid smokers with smokers in the general population of
      western New York. METHODS: This report summarizes findings from two cross
      sectional studies conducted in western New York State during 2002 to 2003: (1)
      Medicaid smokers (n = 1,174) completed an interviewer-administered questionnaire
      in the Office of Medicaid Management and (2) smokers from the general population
      (n = 852) completed a telephone survey. RESULTS: The majority of Medicaid smokers
      (54%) remain unaware of the program benefit providing coverage for smoking
      cessation pharmacotherapies. Medicaid smokers were much less likely (odds ratio =
      0.33, 95% confidence interval = 0.25-0.44) than the general population to report
      having ever used pharmacotherapies. CONCLUSIONS: Highlighting the availability of
      the smoking cessation pharmacotherapy benefit to Medicaid program participants
      may be one strategy to enhance quit attempts among this population. Future
      research should identify other potential barriers to the use of effective
      pharmacotherapies among poorer smokers.

PMID- 15958935
TI  - Correlates of attitudes toward a smoking ban in vehicles.
AB  - To examine the predictors of attitudes toward a smoking ban in vehicles, a
      computer-assisted telephone interview was conducted for a representative sample
      of Indiana adult residents using the random-digit-dialing method. Less than one
      third of the total respondents favored a smoking ban for car drivers and
      passengers, whereas about two thirds favored the smoking ban in public places.
      Fifty-four percent and 63 percent of nonsmokers opposed the smoking ban for car
      drivers and passengers, respectively. Religiosity was a significant predictor for
      attitudes toward a smoking ban for both drivers and passengers when controlling
      for other predictors, including smoking status, employment status, and age group.
      Gender, income group, and race/ethnicity were insignificant.

PMID- 15958936
TI  - Public health capacity building in southeastern Europe: a partnership between the
      Open Society Institute and the US Centers for Disease Control and Prevention.
AB  - The political disintegration of former Yugoslavia inaugurated in 1991 resulted in
      the decentralization of health systems in the federation's successor nation
      states. Efforts by the Open Society Institute improved public health planning and
      management needs consequent to health sector changes. Beginning in Croatia in
      2001, the Institute developed ongoing collaborations between Andrija Stampar
      School of Public Health and the US Centers for Disease Control and Prevention. In
      2003 and 2004, it expanded its project to include the republics of Macedonia and
      of Serbia and Montenegro.

PMID- 15958937
TI  - Beyond lifestyle interventions in diabetes: a rationale for public and economic
      policies to intervene on social determinants of health.

PMID- 15958938
TI  - Factors associated with tuberculosis treatment interruption in New York City.
AB  - SETTING: Large urban tuberculosis control program. OBJECTIVES: To determine the
      frequency and characteristics of treatment interruptions, and the factors
      associated with the different types of treatment interruptions. DESIGN: This was
      a case-control study using culture-positive tuberculosis (TB) patients verified
      in 1998-1999. Case patients included those in whom any of the following mutually
      exclusive categories of treatment interruption: default with return to therapy,
      directly observed therapy nonadherence, default without return to therapy, or
      multiple types of interruptions. Controls were selected randomly from the cohort.
      RESULTS: Overall, 6.0 percent of patients had treatment interruptions. All types
      of treatment interruption were associated with prolonged treatment course and
      decreased treatment completion rates. The median number of months to treatment
      interruption was 4.0 (range, 0.5-28.9 months). Two factors were significantly
      associated with every type of interruption: homelessness and lack of awareness of
      the severity of TB disease. In multivariate analysis, only lack of awareness of
      the severity of disease remained independently associated with all interruption
      types. CONCLUSION: Efforts to improve patients' understanding of TB disease and
      related treatment issues may be an important TB control program strategy and
      should be emphasized at the initiation of therapy and at intervals throughout the
      treatment course to minimize treatment interruption.

PMID- 15958939
TI  - Selecting partners and setting the stage.

PMID- 15958940
TI  - Rationing the flu vaccine.

PMID- 15958941
TI  - Full-use preparedness: addressing the 2004-2005 influenza vaccine shortage.

PMID- 15959094
TI  - Managing heart failure: what you need to know.
AB  - Find out more about this common disorder, from assessing symptoms to answering
      your patient's questions about the newest treatments.

PMID- 15959096
TI  - Take the load off by choosing the right support surface.
AB  - Bewildered by the plethora of choices in pressure-reducing surfaces? Find out how
      they work so you can choose wisely and appropriately.

PMID- 15959097
TI  - Giving your patient a voice with a tracheostomy speaking valve.

PMID- 15959098
TI  - 4 reasons to consider travel nursing.
AB  - Personal and professional growth--not to mention a chance to explore the country-
      are awaiting nurses who decide it's time to give travel nursing a try.

PMID- 15959355
TI  - Pedicle screw placement in the thoracic spine: a comparison of image-guided and
      manual techniques in cadavers.
AB  - STUDY DESIGN: A cadaveric study comparing image guidance technology to
      fluoroscopic guidance as a means of pedicle screw placement in the thoracic
      spine, using a unique starting point for screw placement. OBJECTIVE: To assess
      accuracy of thoracic pedicle screw placement using image guidance versus
      fluoroscopic guidance for screw insertion. SUMMARY OF BACKGROUND DATA: While use
      of pedicle screws in the thoracic spine has been increasing, its adoption has
      been slower than for the lumbar spine, reflecting concern regarding possible
      vascular or spinal cord injury due to screw malplacement. Given these risks,
      efforts to improve the accuracy of thoracic pedicle screw placement remain
      appropriate. Stereotactic guidance has been applied in other aspects of spinal
      surgery to improve the accuracy of instrumentation placement. METHODS: Pedicle
      screws were placed in the thoracic spines of eight cadavers, using either a
      stereotactic guidance or a manual, fluoroscopically guided technique. A slightly
      more superior and lateral starting point from prior descriptions was used. Each
      cadaver was instrumented with pedicle screws in the upper thoracic (T1-T2),
      middle thoracic (T4-T7), and lower thoracic (T9-T10) regions. In the upper and
      middle thoracic regions, screws with a 4.0-mm shank diameter were used while in
      the lower thoracic region a shank diameter of 4.5 mm was used.
      Postinstrumentation CT scans, followed by anatomic dissections, were used to
      evaluate screw exit rates and orientation relative to the pedicle axis. Exit
      rates for the two techniques and the effect of vertebral level on exit rate were
      compared using a chi analysis. The effect of pedicle diameter was tested using a
      Pearson correlation coefficient. RESULTS: No significant differences in the
      overall exit rates or orientation were found between the two techniques. There
      were significant differences in exit rates between the middle (47%), compared
      with the upper (9%) and lower (16%) thoracic regions, respectively (P < 0.001). A
      significant correlation between pedicle diameter and exit rate was also found (P
      < 0.0001). CONCLUSION: Our study showed no significant differences in the overall
      exit rates between the two techniques. Image guidance may increase confidence of
      surgeons with limited experience in thoracic pedicle screw placement. Successful
      placement of screws within the pedicle varies with the anatomic diameter of the
      pedicle itself. Concerns regarding accuracy of screw placement should be greatest
      in the middle thoracic vertebrae (T4-T7), where pedicle diameters are smallest
      and proximity of the great vessels is nearest.

PMID- 15959356
TI  - Giant cell tumor: a case report of recurrence during pregnancy.
AB  - STUDY DESIGN: Descriptive. OBJECTIVE: To report a case of a recurrent giant cell
      tumor (GCT) of the lumbar spine during pregnancy. SUMMARY OF BACKGROUND DATA: GCT
      is a locally aggressive tumor that primarily occurs in young female adults. These
      tumors rarely present in the spine, recur locally, and may be present during
      pregnancy because of growth promoting receptors. METHODS: A 31-year-old pregnant
      woman presented to us from Europe at 24 weeks' gestation (G1P1) with severe back
      pain and an enlarging mass. A large, firm, nontender mass was palpable in the
      right upper quadrant. Radiographs of the lumbar spine were obtained and revealed
      a 10-cm x 8 cm x 15 cm expansive bony mass at L2 with vertebral body collapse and
      junctional kyphosis. Following delivery of a healthy 6 lb. 8 oz. baby, MRI, CT,
      and full-length standing radiographs were obtained. A needle-guided biopsy showed
      amorphous bone with numerous giant cells consistent with a GCT. At 6 weeks
      postpartum, the tumor was resected. RESULTS: At 1-year follow-up, there is no
      evidence of local reoccurrence and the patient is without constitutional
      symptoms. CONCLUSION: This is an unusual presentation of an expanding intra
      abdominal mass originating from the lumbar spine during pregnancy. It most likely
      represents rapid growth of a previous unrecognized recurrence of a GCT. Close
      observation and follow-up CT scanning are imperative to identify and treat GCTs
      of the spine before rapid growth occurs.

PMID- 15959357
TI  - Bone lymphangiomatosis: treatment with percutaneous cementoplasty.
AB  - STUDY DESIGN: Case report, minimally invasive technique. OBJECTIVES: Disseminated
      lymphangiomatosis is a rare disorder that can produce clinical manifestation
      secondary to soft tissue, visceral and bone involvement. The overall prognosis of
      this disorder is usually poor, and the current treatment options for its sequelae
      are limited and only palliative. In this report, we present the use of
      cementoplasty in the percutaneous treatment of a sacral lymphangiomatous bone
      lesion producing severe pain. SUMMARY OF BACKGROUND DATA: Disseminated
      lymphangiomatosis is a rare disorder that can produce clinical manifestation
      secondary to soft tissue, visceral, and bone involvement. Major morbidity related
      to skeletal involvement requiring surgical intervention is less common than that
      related to visceral involvement, but it has been reported in a few case reports
      to palliate neurologic sequelae secondary to vertebral involvement. We present
      case of osteoplasty used to treat a painful osteolytic sacral lesion in a patient
      with diffuse lymphangiomatosis. Computed tomography guided osteoplasty injecting
      acrylic bone cement into the lesion resulted in almost immediate reduction in
      pain. METHODS: The technique and results of minimally invasive percutaneous
      computed tomography-guided cementoplasty of a painful osteolytic sacral lesion
      resulting from chylous reflux in a patient with lymphangiomatosis is presented.
      RESULTS: Computed tomography was used to accurately position a 13-gauge needle
      into a dominant sacral osteolytic lesion. The injection of bone cement into the
      sacral lesion was then monitored by intermittent CT imaging. The patient reported
      substantial pain relief within several hours of the procedure. CONCLUSION: The
      case presented demonstrates the feasibility and efficacy of computed tomography
      guided cementoplasty used to palliate unusual causes of benign osteolytic bone
      lesions. These procedures can be performed as outpatients with minimal recovery.

PMID- 15959358
TI  - Intracranial hypotension induced by cervical spine chiropractic manipulation.
AB  - STUDY DESIGN: Case report. OBJECTIVES: We report a case of intracranial
      hypotension ensuing after a spinal chiropractic manipulation leading to
      cerebrospinal fluid (CSF) isodense effusion in the upper cervical and thoracic
      spine. SUMMARY OF BACKGROUND DATA: The etiology of intracranial hypotension is
      not fully understood, but CSF leakage from spinal meningeal diverticula or dural
      tears may be involved. METHODS: A 36-year-old woman presented with neck and both
      shoulder pain 4 days earlier. She undertook a spinal chiropractic manipulation.
      After this maneuver, she complained of a throbbing headache with nausea and
      vomiting. Her headache worsened, and lying down gave the only measure of limited
      relief. In CSF study, it showed dry tapping. Brain MRI showed pachymeningeal
      gadolinum enhancement. Thoracic spine MRI showed CSF leakage. After admission to
      the hospital, she was treated by hydration and pain control over several days.
      However, her headache did not improve. RESULTS: She was treated by epidural blood
      patch. Afterwards, her headache was improved. This is the first case of
      spontaneous intracranial hypotension in which spinal chiropractic manipulation
      coincided with the development of symptoms and in which a CSF collection in the
      upper cervical and thoracic spine was demonstrated radiographically in Korea.
      CONCLUSIONS: From this case, we can understand the etiology of intracranial
      hypotension and consider the complication of chiropractic manipulation.

PMID- 15959359
TI  - Transient paraparesis after laminectomy for thoracic myelopathy due to
      ossification of the posterior longitudinal ligament: a case report.
AB  - STUDY DESIGN: Case report. OBJECTIVES: We report a case with thoracic myelopathy
      due to ossification of the posterior longitudinal ligament (OPLL) of the spine,
      in which neurologic deterioration progressed after laminectomy and was markedly
      reversed after additional posterior instrumented fusion. SUMMARY OF BACKGROUND
      DATA: Many different surgical procedures may be used in the treatment of thoracic
      OPLL. However, the possibility of postoperative paraplegia remains a major risk,
      and consistent protocols and procedures for surgical correction of thoracic OPLL
      have not been established. METHODS: The patient was a 53-year-old man with
      continuous OPLL at T3-T8 that compressed the spinal cord anteriorly. Anterior
      decompression surgery employing a posterior approach was initiated, but during
      OPLL extirpation electrophysiologic monitoring of spinal cord activity showed
      abnormalities. As a result, the procedure was converted to a wide laminectomy.
      Over the next 4 weeks, kyphosis of the thoracic spine increased and myelopathy
      worsened, producing severe paraparesis. RESULTS: Four weeks after surgery,
      posterior instrumented fusion (T1-L1) was performed without correction of the
      kyphosis. After the fusion, neurologic deficits gradually recovered and the
      patient was fully recovered after 10 months. At follow-up 15 years after the
      fusion, no neurologic deterioration was seen despite the presence of residual
      anterior impingement of spinal cord by OPLL. CONCLUSIONS: The present case
      suggests that kyphosis and instability are major factors that affect the severity
      of thoracic myelopathy due to OPLL, and posterior fusion with spinal
      instrumentation is a safe and effective adjunct procedure for surgical treatment
      of thoracic OPLL.

PMID- 15959361
TI  - Harrington lecture: the future of academic spine surgery: challenges and
      opportunities.

PMID- 15959362
TI  - A multicenter, prospective, randomized trial evaluating the X STOP interspinous
      process decompression system for the treatment of neurogenic intermittent
      claudication: two-year follow-up results.
AB  - STUDY DESIGN: A randomized, controlled, prospective multicenter trial comparing
      the outcomes of neurogenic intermittent claudication (NIC) patients treated with
      the interspinous process decompression system (X STOP) with patients treated
      nonoperatively. OBJECTIVE: To determine the safety and efficacy of the X STOP
      interspinous implant. SUMMARY OF BACKGROUND DATA: Patients suffering from NIC
      secondary to lumbar spinal stenosis have been limited to a choice between
      nonoperative therapies and decompressive surgical procedures, with or without
      fusion. The X STOP was developed to provide an alternative therapeutic treatment.
      METHODS.: 191 patients were treated, 100 in the X STOP group and 91 in the
      control group. The primary outcomes measure was the Zurich Claudication
      Questionnaire, a patient-completed, validated instrument for NIC. RESULTS: At
      every follow-up visit, X STOP patients had significantly better outcomes in each
      domain of the Zurich Claudication Questionnaire. At 2 years, the X STOP patients
      improved by 45.4% over the mean baseline Symptom Severity score compared with
      7.4% in the control group; the mean improvement in the Physical Function domain
      was 44.3% in the X STOP group and -0.4% in the control group. In the X STOP
      group, 73.1% patients were satisfied with their treatment compared with 35.9% of
      control patients. CONCLUSIONS: The X STOP provides a conservative yet effective
      treatment for patients suffering from lumbar spinal stenosis. In the continuum of
      treatment options, the X STOP offers an attractive alternative to both
      conservative care and decompressive surgery.

PMID- 15959363
TI  - Configuration of the connective tissue in the posterior atlanto-occipital
      interspace: a sheet plastination and confocal microscopy study.
AB  - STUDY DESIGN: The connective tissue structures in the posterior atlanto-occipital
      region were investigated using E12 sheet plastinations and confocal microscopy.
      OBJECTIVES: To define the relationship between rectus capitis posterior minor
      (RCPm), posterior atlanto-occipital (PAO) membrane, nuchal ligament, and the
      spinal dura in the PAO interspace. SUMMARY OF BACKGROUND DATA: It has been
      speculated that connections between the dura and muscles and/or ligaments in the
      PAO interspace may transmit forces from the cervical spine joint complexes to the
      pain-sensitive dura, generating cervicogenic headaches. Anatomic structures
      involved in these connections include the RCPm, PAO membrane, and nuchal
      ligament. However, there is little information about the nature of these
      connections and the relationships between these anatomic structures. METHODS: The
      study used a combined approach, consisting of the gross anatomic dissection of
      nine cadavers and the E12 sheet plastination method for thirteen adult human
      cadavers, five of which were further examined using confocal microscopy. RESULTS:
      The study demonstrates that (1) the tendinous fibers from the medial and deep
      part of the RCPm muscle are continuous antero-inferiorly with the spinal dura;
      (2) the PAO membrane is part of the RCPm fascia and tendon and the perivascular
      sheathes; (3) antero-inferiorly the PAO membrane fuses with the spinal dura
      rather than the atlas; and (4) the nuchal ligament does not exist in the PAO
      interspace. CONCLUSIONS: The connective tissue structures that connect the spinal
      dura to the RCPm muscle in the PAO interspace are the RCPm fascia and tendinous
      fibers and perivascular sheathes.

PMID- 15959364
TI  - Recording of neural activity from goat cervical facet joint capsule using custom
      designed miniature electrodes.
AB  - STUDY DESIGN: To establish a methodology for the neurophysiologic study of
      mechanoreceptors in the cervical facet joint capsule. OBJECTIVES: To test a
      custom designed miniature dual bipolar electrode for recording the neural
      activity in cervical dorsal roots. To determine if the neural activity from
      different receptors in the capsule can be differentiated using this methodology.
      SUMMARY OF BACKGROUND DATA: Injury to cervical facet joint capsules has been
      regarded as an important source of whiplash pain, but no neurophysiologic study
      has been performed to demonstrate or characterize sensory nerve function in the
      capsule. METHODS: Nineteen goats weighing 34 to 55 kg were used under general
      anesthesia. A C4-C6 laminectomy was performed to expose the C6 nerve root. Custom
      designed miniature dual bipolar electrodes were used to record neural activity in
      the left C6 branches. Electrical and mechanical stimuli were used to evoke
      receptor activity in the dorsal aspect of the C5/6 capsule. Conduction velocities
      (CVs) of evoked units were determined by electrical stimulation and dual-bipolar
      electrode recording methods. The units were classified based on their CVs. The
      waveform of each classified unit was saved as a template for later single unit
      discharge search among multiunit discharges during the stretch of the capsule.
      The C5/6 facet joint with capsule was pulled by a computer-controlled actuator
      instrumented with a load cell at a rate of 0.5 mm per second. The evoked neural
      activity and load were recorded, digitized, and analyzed to determine CV,
      discharge rate, and response to the stretch. RESULTS: Miniature bipolar
      electrodes recorded the neural activity in both channels, with single unit CVs
      being measured. There was no discernible motion between the electrode and dorsal
      root when the capsule was pulled. Both local compression and stretch on capsule
      evoked multiunit discharges. A-beta, A-delta, and C-fiber units were found among
      these multiunit discharges. The rate of single unit and multiunit discharges
      increased during capsule stretch in the physiologic range and afterdischarges
      occurred beyond the physiologic range. CONCLUSIONS: The novel miniature
      electrodes not requiring a micromanipulator made it feasible and reliable to
      record neural activity from short cervical spinal roots. Waveforms of different
      units could be identified, making it possible to study sensory functions of the
      facet joint capsule. A-beta, A-delta, and C-fiber units were found responding to
      mechanical stimuli, indicating that facet joint capsule has functional
      proprioceptors and nociceptors.

PMID- 15959365
TI  - Expressions of membrane-type I matrix metalloproteinase, Ki-67 protein, and type
      II collagen by chondrocytes migrating from cartilage endplate into nucleus
      pulposus in rat intervertebral discs: a cartilage endplate-fracture model using
      an intervertebral disc organ culture.
AB  - STUDY DESIGN: Immunohistochemistry was performed in organ-cultured intact and
      cartilage endplate (CE)-fractured rat intervertebral discs (IVDs). OBJECTIVES: To
      demonstrate biologic events associated with migration of chondrocytes from
      hyaline CE into nucleus pulposus (NP). SUMMARY OF BACKGROUND DATA: It was
      recently revealed that the transition from a notochordal NP to a
      fibrocartilaginous NP in the rabbit IVD is accomplished exogenously by
      chondrocytes migrating from CEs into the NP. This observation has not been
      studied in other animal models, and the biologic events associated with
      chondrocyte migration have not been elucidated in the literature. METHODS: IVDs
      including cranial and caudal CEs were obtained from 4-week, 6-month, 12-month,
      and 18-month old Wistar rats. To accelerate chondrocyte migration, CEs of IVDs
      were fractured and cultured for 48 hours. IVDs without CE-fracture were used as a
      control for each age group. Expressions of membrane-type I matrix
      metalloproteinase (MT1-MMP, as a marker for cell migration and extracellular
      matrix digestion) and Ki-67 protein (as a proliferation marker) and pericellular
      deposition of type II collagen (as a marker for fibrocartilaginous matrix) by the
      chondrocytes migrating from CE into NP were examined immunohistochemically.
      RESULTS: In the control groups, chondrocyte migration limited only along the
      periphery of the notochordal NP and no chondrocytes were inside the NP proper.
      However, all the IVDs in the CE-fracture groups showed direct and more extensive
      migration of chondrocytes from CEs into the NP proper. The migrating chondrocytes
      in both control and CE-fracture groups expressed MT1-MMP and Ki-67 protein and
      deposited type II collagen in the NP. CONCLUSIONS: This report demonstrates the
      chondrocyte migration from CE into NP in the organ-cultured rat IVDs. This
      phenomenon is accelerated in the presence of CE fracture. The chondrocytes
      migrating from CEs into the NP expressed MT1-MMP and Ki-67 protein and deposited
      type II collagen. These biologic strategies probably enable chondrocytes of the
      hyaline CE to migrate into the ectopic NP region, replace notochordal cells, and
      change the notochordal tissue into fibrocartilage. These results suggest that
      similar biologic mechanisms may be involved in the natural transition from the
      notochordal NP to the fibrocartilaginous NP in other animal models, including
      human.

PMID- 15959366
TI  - Developmental anomalies of the cervical spine in patients with fibrodysplasia
      ossificans progressiva are distinctly different from those in patients with
      Klippel-Feil syndrome: clues from the BMP signaling pathway.
AB  - STUDY DESIGN: A radiographic analysis of the cervical spine of 70 patients
      diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with
      Klippel-Feil (KF) syndrome was conducted. OBJECTIVES: The objectives of this
      study were to describe cervical spine abnormalities in patients with FOP, to
      compare and contrast those findings with the malformations in patients with KF
      syndrome, and to examine the possible etiology of these abnormalities. SUMMARY OF
      BACKGROUND DATA: Congenital features of diseases often provide seminal clues to
      underlying etiology and developmental pathways. While progressive metamorphosis
      of connective tissue to heterotopic bone is the most dramatic and disabling
      feature of FOP, less severe congenital anomalies of the skeleton are also
      present. Vertebral fusions observed in KF are consistent with defects in
      embryonic segmentation. METHODS: The cervical spine plain films of 70 FOP
      patients and 33 KF patients with documented congenital abnormalities were
      reviewed. RESULTS: Generalized neck stiffness and decreased range of motion were
      noted in most children with FOP. In the FOP patient group, characteristic
      anomalies, including large posterior elements, tall narrow vertebral bodies,and
      fusion of the facet joints between C2 and C7, were observed. Most notably, these
      characteristic anomalies of the cervical spine in patients with FOP were
      distinctly different from those of 33 patients with KF that were examined but
      were strikingly similar to those seen in mice with homozygous deletions of the
      gene-encoding noggin, a bone morphogenetic protein (BMP) antagonist. CONCLUSIONS:
      FOP patients exhibit a characteristic set of congenital spine malformations.
      While the noggin gene (NOG) is not mutated in patients who have FOP, these
      findings extend a growing body of evidence implicating overactivity of the BMP
      signaling pathway in the molecular pathogenesis of FOP.

PMID- 15959367
TI  - Strut allograft union and remodeling using rhBMP-2 in a spinal corpectomy model.
AB  - STUDY DESIGN: Growth factor in a collagen sponge carrier was compared to
      autograft, both packed within an allograft strut following corpectomy in a bovine
      spinal model. OBJECTIVE: To evaluate incorporation of cortical strut allografts
      after lumbar corpectomy, comparing augmentation with recombinant human bone
      morphogenetic protein-2 (rhBMP-2) to local autograft. SUMMARY OF BACKGROUND DATA:
      Autogenous strut grafts are the gold standard for successful fusion in
      reconstruction following corpectomy; however, significant donor site morbidity
      can occur. Recent studies describing consistently successful anterior interbody
      fusions with BMP augmentation suggest an exciting prospect of unlimited and
      potent grafting material for these difficult fusions. METHODS: Sixteen calves
      underwent L3 corpectomy with instrumented strut allograft reconstruction. The
      rhBMP-2 impregnated collagen sponges filled the empty medullary canal of the
      allograft in 8 animals. Eight animals had the allograft strut filled with local
      autogenous bone. After 4 months, the lumbar spines were harvested for
      radiographic, biomechanical, and histologic evaluation. RESULTS: Computerized
      tomography revealed allograft fusion in 7 of 8 autograft specimens and 8 of 8 BMP
      specimens. The BMP treated group had denser bone at the ends of the cortical
      allograft, but a central void persisted. Autograft filled struts maintained a
      more uniform distribution of less organized bone throughout the strut canal.
      Histologic assessment verified remodeling and incorporation of the allografts for
      both groups. Biomechanical testing confirmed no significant difference in fusion
      strength between groups. CONCLUSIONS: Large cortical strut allografts (after
      lumbar corpectomy) supplemented with rhBMP-2 had incorporation and fusion
      strength comparable to allografts enhanced with cancellous autograft.

PMID- 15959368
TI  - Biomechanical comparison of lumbosacral fixation using Luque-Galveston and
      Colorado II sacropelvic fixation: advantage of using locked proximal fixation.
AB  - STUDY DESIGN: Biomechanical evaluation of sacropelvic fixation strategies as they
      apply to neuromuscular scoliosis. OBJECTIVES: The primary objective was to
      compare the rigidity of 2 methods of sacropelvic fixation (Galveston vs. Colorado
      II). The secondary objective was to evaluate the effect on construct rigidity by
      adding a pair of L1 pedicle screws to a Luque wire construct. SUMMARY OF
      BACKGROUND DATA: The Galveston modification to the Luque rodding system has
      become standard for treating childhood and adolescent neuromuscular scoliosis.
      The Galveston method provides reasonable lumbo-pelvic fixation with a relatively
      simple method of insertion. Clinical reviews of sagittal plane stability in
      neuromuscular patients with Galveston fixations performed at our institution have
      led to concerns regarding the technique's ability to maintain proper lumbar
      lordosis. This concern has generated interest in evaluating biomechanical
      stability of more rigid fixation methods in these long spino-pelvic constructs.
      As such, the following biomechanical study evaluated lumbosacral stability of 2
      sacropelvic fixation methods: the standard Luque-Galveston method and the
      Colorado II sacropelvic fixation method using the Chopin plate-screw block. As a
      secondary interest, evaluations of the rigidity of the proximal construct when
      using pedicle screw fixation were completed. It was hypothesized that one
      additional point of rigid fixation at the thoracolumbar junction may make
      substantial improvement in rigidity to the otherwise Luque construct. METHODS:
      Lumbo-pelvic segments of human cadaveric specimens were instrumented with L1
      pedicle screws, sublaminar wires between L2 and L5, and sacropelvic fixation with
      either Galveston rods or Colorado II sacropelvic plates using S1 screws, S2 alar
      screws, and iliac screws. Tests were conducted for physiologic flexion-extension
      and torsional loading. Construct stiffness between L1-S1 was determined for each
      specimen. Motion measurement data were collected between L1-L5 and L5-S1 using a
      noncontact marker system. Statistical analysis included a 2 -way analysis of
      variance (dependent variables: construct/locked screw) with the Tukey post hoc
      correction for multiple comparisons (P < 0.05). RESULTS: The flexion and
      extension bending stiffness of the construct was similar between the Galveston
      and Colorado II constructs. Both constructs were stiffer when the L1 screws were
      locked rigidly to the rod. Torsional stiffness followed similar trends with no
      significant difference between the systems, although more rigid in more cases
      when the L1 screws were locked to the rod. Regarding limiting L5-S1 motion during
      flexion and extension loading, the Colorado II construct did so to a higher
      degree. There was no difference in torsional motion between the 2 constructs.
      Locking the L1 pedicle screws reduced torsional motion but had no effect on
      flexion-extension motion at L5-S1. CONCLUSION: The 2 methods of sacropelvic
      fixation provided similar construct stiffness, although the Colorado II method
      had less L5-S1 motion on flexion-extension testing, and the Galveston construct
      tended (although not statistically) to be stiffer in torsional loading. The
      addition of a pair of L1 pedicle screws increased the construct stiffness for
      both constructs by approximately 50%.

PMID- 15959369
TI  - Early failures following cervical corpectomy reconstruction with titanium mesh
      cages and anterior plating.
AB  - STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate the use of
      titanium mesh cages in the reconstruction of the cervical spine following
      corpectomy. SUMMARY OF BACKGROUND DATA: Previous studies have shown high
      successful fusion rates and low failure rates with this technique. Similar
      reconstruction techniques using anterior strut bone grafting and anterior plating
      have shown higher failure rates following multilevel corpectomies. METHODS: A
      retrospective review was performed of 23 consecutive patients who underwent
      anterior cervical corpectomy reconstructed with a titanium mesh cage, local
      autograft, and fixed anterior plating. Medical records and radiographs were
      reviewed. Average follow-up was 28 months. RESULTS: Seven patients (30%) had
      reconstruction failures. There was 1 failure (6%) in the 1-level corpectomy group
      and 6 (75%) in the multilevel corpectomy group. All failures occurred before 12
      weeks after surgery. The remaining patients had successful fusion (70%).
      CONCLUSION: There is a high early failure rate (75%) with the use of a titanium
      mesh cage and fixed anterior plating for reconstruction of multilevel
      corpectomies. Posterior fusion and instrumentation should be considered when
      using this technique for multilevel reconstructions.

PMID- 15959370
TI  - Correlation between range of motion and outcome after lumbar total disc
      replacement: 8.6-year follow-up.
AB  - STUDY DESIGN: Retrospective radiographic and chart review. OBJECTIVE: To examine
      the relationship between lumbar total disc replacement (TDR) range of motion
      (ROM) and clinical outcome at 8.6-year follow-up. SUMMARY OF BACKGROUND DATA:
      There are no studies on the relationship between TDR motion and clinical
      outcomes. METHODS: We reviewed 38 patients who underwent 1 or 2-level TDR
      implantation with 51 TDR. Flexion-extension ROM was measured on lateral
      radiographs. Clinical outcomes were measured at 8.6 years by modified Stauffer
      Coventry scores, Oswestry Disability Questionnaires (ODQ), and subjective ratings
      of back pain, leg pain, and disability. Spearman rank correlation coefficient was
      used to determine if ROM was correlated with clinical outcome. Patients were
      divided into 2 groups by motion (< or = 5 degrees and > 5 degrees ). Statistical
      differences in outcome were sought. RESULTS: Spearman rank correlation
      coefficient revealed weak-to-moderate but statistically significant associations
      between ROM and outcome for postoperative back pain (r = -0.35, P = 0.034), ODQ
      (r = -0.33, P = 0.046), and modified Stauffer-Coventry scores (r = 0.42, P =
      0.0095). Patients with motion of > 5 degrees had superior outcomes in ODQ (mean
      difference 12.6 points, P = 0.026) and Stauffer-Coventry scores (mean difference
      2.2 points, P = 0.015). CONCLUSIONS: The radiographic ROM at 8.6-year follow-up
      was positively correlated with several outcomes measures. Patients with motion >
      5 degrees had clinically modest but statistically better outcomes in ODQ and
      modifiedStauffer-Coventry scores. Longer follow-ups will be necessary to measure
      fully the impact of TDR ROM on outcome.

PMID- 15959371
TI  - Spinal cord stimulation for axial low back pain: a prospective, controlled trial
      comparing dual with single percutaneous electrodes.
AB  - STUDY DESIGN: A prospective, controlled, clinical trial comparing single and dual
      percutaneous electrodes in the treatment of axial low back pain from failed back
      surgery syndrome. OBJECTIVES: To clarify technical requirements and test the
      hypothesis that placing two linear arrays in parallel, thereby doubling the
      number of contacts, improves outcome. SUMMARY OF BACKGROUND DATA: Technical
      improvements have enhanced outcomes of spinal cord stimulation for chronic axial
      low back pain. Dual, parallel electrodes reportedly improve these outcomes.
      METHODS: Acting as their own controls, 20 patients who passed screening with
      single, 4-contact electrodes received permanent dual, 4-contact electrodes with 7
      or 10-mm intercontact distances at the same vertebral level(s). We quantified
      and compared the technical and clinical results of the single and dual
      electrodes, adjusting stimulation parameters to specific psychophysical
      thresholds. RESULTS: Single electrodes provided significant (P < 0.01) advantages
      in patient- and computer-calculated ratings of pain coverage by paresthesias and
      in the scaled amplitude necessary to cover the low back, compared with dual 7-mm
      electrodes. Slight advantages without statistical significance were observed for
      the single over the dual 10-mm electrodes. Amplitude requirements were
      significantly lower for the single electrode than for either dual electrode. At
      long-term follow-up, 53% of patients met the criteria for clinical success.
      CONCLUSIONS: While we observed disadvantages for dual electrodes in treating
      axial low back pain, we achieved technical success with single or dual electrodes
      in most patients and maintained this success clinically with dual electrodes in
      53%.

PMID- 15959372
TI  - A new operative classification of idiopathic scoliosis: a peking union medical
      college method.
AB  - STUDY DESIGN: A retrospective radiographic study on the type of surgically
      treated idiopathic scoliosis, with a prospective study on the reliability of the
      type-related fusion guide. OBJECTIVES: To identify and classify surgically
      treated idiopathic scoliosis, and define its related fusion levels by a new
      classification system. SUMMARY OF BACKGROUND DATA: Some classification methods
      for idiopathic scoliosis have been suggested. However, poor intraobserver
      reproducibility and interobserver reliability were experienced in these studies,
      and were not appropriate for guiding surgical planning. METHODS: A total of 427
      surgically treated idiopathic scoliosis cases were reviewed. Preoperative and
      postoperative standing anteroposterior, lateral, and preoperative supine side
      bending radiograph were analyzed using the Scoliosis Research Society definition
      of scoliosis and curve apex. The resulting classification was tested for
      intraobserver reliability and interobserver reliability, and by 6 surgeons.
      Apical frequencies were determined for each type, and prospective surgical
      testing of the new type and its related fusion guide was performed. RESULTS:
      Three major types and 13 subtypes were identified, of which the Peking Union
      Medical College type I accounted for 56.62%, type II 42.16%, and type III 1.22%.
      The interobserver reliability testing was 85% (kappa coefficient 0.832), while
      intraobserver reproducibility was 91% (kappa coefficient 0.898). Each type had
      its corresponding fusion levels. A prospective study of 152 cases was performed
      according to the classification. All of these cases were followed over 18 months,
      and no postoperative decompensation was noted. CONCLUSION: The Peking Union
      Medical College classification of idiopathic scoliosis is one system to combine
      each type with its corresponding fusion level, and it had much higher
      interobserver reliability and intraobserver reproducibility than the King system.
      Further prospectivestudies would help to clarify and expand this system.

PMID- 15959373
TI  - A blinded assessment of radiographic criteria for atlanto-occipital dislocation.
AB  - STUDY DESIGN: Blinded comparison of 5 methods to diagnose atlanto-occipital
      dislocation (AOD) on plain radiographs and computerized tomography (CT) of the
      cervical spine. OBJECTIVE: To determine the best method to diagnose AOD. SUMMARY
      OF BACKGROUND DATA: Several methods are proposed for the diagnosis of AOD,
      including the Power's ratio, X-line method, basion-dens interval, condylar gap,
      and Harris method. No blinded comparison of the results of these methods has been
      compared to patient outcome, and there is no information available regarding the
      accuracy of these methods applied to CT scans. METHODS: Plain lateral radiographs
      and CTs of the cervical spine were reviewed in 104 patients, including 6 with
      AOD. Images underwent a blinded review by a board certified neurosurgeon
      (D.K.R.), orthopedist (P.A.A.), radiologist (J.C.), and emergency physician
      (D.B.B.). Each diagnostic method for AOD was applied for determination of
      sensitivity, specificity, and positive and negative predictive values. The
      ability to identify relevant anatomic landmarks was also tabulated. RESULTS:
      Average values for sensitivities, specificities, positive and negative predictive
      values for each method applied to plain radiographs are: 0.4625-1.0, 0.8933
      0.9725, 0.2775-0.45, and 0.975-1.0, respectively. These values for each method
      applied to CT scans are: 0.7075-1.0, 0.8725-0.9775, 0.3175-1, and 0.98-1.0,
      respectively. Identification of relevant anatomic landmarks occurred 99.75% of
      the time when these methods were applied to CT scans compared to 39% to 84% of
      the time on plain radiographs. CONCLUSIONS: Sensitivity, specificity, positive
      and negative predictive values of these methods improve when applied to CT scans
      because of better visualization of anatomic landmarks. This result suggests CT
      scans of the cervical spine may be warranted in all trauma patients suspected of
      having cervical spine injury.

PMID- 15959374
TI  - Classification in nonspecific low back pain: what methods do primary care
      clinicians currently use?
AB  - STUDY DESIGN: Postal survey. OBJECTIVES: To describe the signs and symptoms that
      clinicians think represent nonspecific low back pain (NSLBP) subgroups, and to
      report the labels that clinicians give to those subgroups. SUMMARY OF BACKGROUND
      DATA: The cause of most low back pain (LBP) cannot be diagnosed. Consequently,
      approximately 80% of primary care LBP presentations are most accurately labeled
      as NSLBP. Most Australian primary care clinicians think that NSLBP is
      heterogeneous and treat patients differently based on that heterogeneity. This
      research sought to identify the subgroups clinicians believe are recognizable
      within that heterogeneity. METHODS: Analysis of survey data from 651 primary care
      clinicians from 6 professional disciplines: physiotherapy, manipulative
      physiotherapy, chiropractic, osteopathy, general medicine, and musculoskeletal
      medicine. RESULTS: There was little consensus among participating clinicians
      regarding the signs and symptoms that identify NSLBP subgroups. Most clinicians
      give labels to NSLBP subgroups that imply putative pathoanatomy, however, the
      evidence that these labels are valid is scant and controversial. CONCLUSIONS: A
      lack of consensus among participating clinicians regarding NSLBP subgroups and a
      lack of evidence for the validity of NSLBP subgrouping are a compelling argument
      for further research into this clinical practice.

PMID- 15959375
TI  - United States trends in lumbar fusion surgery for degenerative conditions.
AB  - STUDY DESIGN: Retrospective cohort study using national sample administrative
      data. OBJECTIVES: To determine if lumbar fusion rates increased in the 1990s and
      to compare lumbar fusion rates with those of other major musculoskeletal
      procedures. SUMMARY OF BACKGROUND DATA: Previous studies found that lumbar fusion
      rates rose more rapidly during the 1980s than did other types of lumbar surgery.
      METHODS: We used the Healthcare Cost and Utilization Project Nationwide Inpatient
      Sample from 1988 through 2001 to examine trends. U.S. Census data were used for
      calculating age and sex-adjusted population-based rates. We excluded patients
      with vertebral fractures, cancer, or infection. RESULTS: In 2001, over 122,000
      lumbar fusions were performed nationwide for degenerative conditions. This
      represented a 220% increase from 1990 in fusions per 100,000. The increase
      accelerated after 1996, when fusion cages were approved. From 1996 to 2001, the
      number of lumbar fusions increased 113%, compared with 13 to 15% for hip
      replacement and knee arthroplasty. Rates of lumbar fusion rose most rapidly among
      patients aged 60 and above. The proportion of lumbar operations involving a
      fusion increased for all diagnoses. CONCLUSIONS: Lumbar fusion rates rose even
      more rapidly in the 90s than in the 80s. The most rapid increases followed the
      approval of new surgical implants and were much greater than increases in other
      major orthopedic procedures. The most rapid increases in fusion rates were among
      adults aged 60 and above. These increases were not associated with reports of
      clarified indications or improved efficacy, suggesting a need for better data on
      the efficacy of various fusion techniques for various indications.

PMID- 15959377
TI  - Prognosis or "curabo effect?": physician prediction and patient outcome of
      surgery for low back pain and sciatica.
AB  - STUDY DESIGN: Prospective study with patient and physician questionnaires,
      clinical records, and imaging. OBJECTIVE: To compare physician expectations of
      surgery for sciatica and patient outcome. SUMMARY OF BACKGROUND DATA: Physician
      accuracy in identifying individual patient prognosis is important for therapeutic
      decisions. METHODS: A total of 197 consecutive patients with low back pain and/or
      sciatica who underwent low back surgery in the University Hospital of Lausanne,
      Switzerland. RESULTS: Physicians predicted "a great improvement" of quality of
      life after surgery for 79% and "moderate improvement" for 20% (1% others); 39% of
      patients had no "minimal clinically important difference" in back pain after
      surgery, despite physician prediction of "great improvement." Correlations
      between physician expectation and various dimensions of patient outcome were not
      significant, and agreement with patient global judgment of 1-year outcome was
      poor (kappa = 0.03). However, in a subgroup where the indication for treatment
      was not considered appropriate, physician prediction of "great improvement" was
      followed by greater improvement outcome on SF-36 mental component score (P =
      0.05), mental health (0.02), and general health (0.03) compared with patients
      where the physician did not predict "great improvement." CONCLUSION: Despite
      clear average improvement, surgeons tended to give overly optimistic predictions
      that were not correlated with patient outcome. For patients receiving a treatment
      not meeting explicit criteria of appropriateness, more optimistic physician
      expectation was associated with better improvement of psychological dimensions.
      Besides prognostic ability, the influence of physician expectation on patient
      outcome is discussed and the concept of "curabo effect" (differentiated from
      "placebo effect") proposed.

PMID- 15959379
TI  - The role of alternative medical providers for the outpatient treatment of insured
      patients with back pain.
AB  - STUDY DESIGN: Analysis of health insurance claims from 2 large Washington State
      companies. OBJECTIVE: To evaluate the prevalence and cost of complementary and
      alternative medicine (CAM) provider use for back pain treatment. SUMMARY OF
      BACKGROUND DATA: Washington State requires all commercial insurance to cover
      licensed CAM providers. METHODS: Outpatient claims for the treatment of back pain
      were analyzed by the International Classification of Disease-9 codes and provider
      type. The number of visits and expenditures associated with different forms of
      treatments were calculated. RESULTS: Back pain accounted for 15% of all
      outpatient visits, and these companies spent more than $52 million on 652,593
      claims submitted by 104,358 adults. Most people used only CAM (43%) or only
      conventional providers (45%) for back pain treatment, with merely 12% using both.
      Patients who saw only CAM providers had fewer comorbidities than the other 2
      groups and made approximately twice as many visits as "conventional only" users
      (median 4 vs. 2). Average amount allowed per outpatient low back pain claim was
      lower for CAM visits (mean $50, SD $28) than for conventional visits (mean $128,
      SD $173). Total outpatient costs for the treatment of back pain were highest for
      the group using both CAM and conventional care (mean $1079, SD $1185), and lowest
      for the group using CAM only (mean $342, SD $429). CONCLUSION: Many people with
      back pain use only CAM for their treatment. Although less expensive, this group
      also appears to be less severely ill. Because of the high prevalence of this
      condition, cost-effectiveness studies that include CAM therapies are still
      warranted.

PMID- 15959380
TI  - Risk factors for infection after spinal surgery.
AB  - STUDY DESIGN: A retrospective case control analysis of 48 cases of postoperative
      infection following spinal procedures. OBJECTIVES: Spinal procedures that became
      infected after surgery were analyzed to identify the significance of preoperative
      and intraoperative risk factors. Characterization of the nature and timing of the
      infections was also performed. SUMMARY OF BACKGROUND DATA: The rate of
      postoperative infection following spinal surgery varies widely depending on the
      nature of the procedure and the patient's diagnosis. Preoperative comorbidities
      and risk factors also influence the likelihood of infection. METHODS: A review of
      1629 procedures performed on 1095 patients revealed that a postoperative
      infection developed in 48 patients (4.4%). Data regarding preoperative and
      intraoperative risk factors were gathered from patient charts for these and a
      randomly selected control group of 95 uninfected patients. For analysis, these
      patient groups were further divided into adult and pediatric subgroups, with an
      age cutoff of 18 years. Preoperative risk factors reviewed included smoking,
      diabetes, previous surgery, previous infection, steroid use, body mass index, and
      alcohol abuse. Intraoperative factors reviewed included staging of procedures,
      estimated blood loss, operating time, and use of allograft or instrumentation.
      RESULTS: The majority of infections occurred during the early postoperative
      period (less than 3 months). Age >60 years, smoking, diabetes, previous surgical
      infection, increased body mass index, and alcohol abuse were statistically
      significant preoperative risk factors. The most likely procedure to be
      complicated by an infection was a combined anterior/posterior spinal fusion
      performed in a staged manner under separate anesthesia. Infections were primarily
      monomicrobial, although 5 patients had more than 4 organisms identified. The most
      common organism cultured from the wounds was Staphylococcus aureus. All patients
      were treated with surgical irrigation and debridement, and appropriate
      antibiotics to treat the cultured organism. CONCLUSIONS: Aggressive treatment of
      patients undergoing complex or prolonged spinal procedures is essential to
      prevent and treat infections. Understanding a patient's preoperative risk factors
      may help the physician to optimize a patient's preoperative condition.
      Additionally, awareness of critical intraoperative parameters will help to
      optimize surgical treatment. It may be appropriate to increase the duration of
      prophylactic antibiotics or implement other measures to decrease the incidence of
      infection for high risk patients.

PMID- 15959381
TI  - Noncommunicating cysts and cerebrospinal fluid flow dynamics in a patient with a
      Chiari I malformation and syringomyelia--part II.

PMID- 15959390
TI  - [Editorial].

PMID- 15959383
TI  - Klippel-Feil syndrome presenting with bilateral thoracic outlet syndrome.

PMID- 15959391
TI  - [Development of adipose tissue and dietary lipids: from basic science to
      medicine].
AB  - Professor Gerard Ailhaud was awarded the 2005 Institut Roche de l'Obesite Prize,
      for his studies on adipocyte biology and the differential role of dietary lipids
      in the increasing prevalence of overweight and obesity. With his colleagues, he
      demonstrated that natural fatty acids play an hormonal role by favouring the
      differentiation of preadipocytes into adipocytes, showed the potent adipogenic
      role of arachidonic acid (C20:4, n-6) and depicted the signaling pathways
      involved in this process. More recently, his research has underscored the
      importance of the composition of dietary fats during the gestation/suckling
      period, i.e. an excess of the essential polyunsaturated fatty acids of the n-6
      series, in the hypertrophic/hyperplasic development of adipose tissue which has
      been associated over the last decades with the increasing prevalence of childhood
      obesity. The main findings of his studies are summarised in this review.

PMID- 15959392
TI  - [Early nutrition and weight evolution in children].
AB  - Maternal nutritional and metabolic factors which affect fetal growth and birth
      weight generate an increasing interest. Some of these factors might affect organs
      growth and functions, or might modify metabolism, toward a greater susceptibility
      to obesity and several chronic diseases (arterial hypertension, type 2 diabetes,
      cardiovascular diseases). Numerous epidemiological data support a negative
      relation between birth weight and these chronic diseases. Other studies indicate
      a positive relation between birth weight and body mass index in childhood or
      adulthood, which may be explained by a reduced lean mass; however, some of them
      suggest that a low birth weight would favored a troncular (central) fat
      distribution. In offsprings of mother with diabetes during pregnancy, a high
      birth weight, clearly predispose to obesity and insulin resistance since infancy,
      thus, demonstrating the deleterious effect of the in utero diabetic environment.
      Recent studies, indicate that even moderate maternal glucose tolerance
      abnormalities, of a lower grade than gestational diabetes, lead to an accelerated
      fetal adiposity growth. Furthermore, an early rapid postnatal growth is also a
      risk factor for children overweight. All these recent data, reinforce the need
      for studies to assess the complex interactions between prenatal and postnatal
      growth and their nutritional and genetic determinants. This is of importance due
      to the increasing number of women who are overweight when becoming pregnant, as
      well as, the regular increase in the prevalence of children overweight and
      obesity.

PMID- 15959393
TI  - [Nutritionnal epigenomics: consequences of unbalanced diets on epigenetics
      processes of programming during lifespan and between generations].
AB  - Epigenetic changes associated with DNA methylation and histone modifications
      leading to chromatin remodeling and regulation of gene expression underlie the
      developmental programming of obesity, type 2 diabetes, cardiovascular diseases
      and metabolic syndrome. This review focuses on converging data supporting the
      hypothesis that, in addition to "thrifty genotype" inheritance, individuals with
      obesity, type 2 diabetes, and metabolic syndrome (MetS) with an increased risk of
      cardiovascular diseases have suffered improper "epigenetic programming" during
      their fetal/postnatal development due to maternal inadequate nutrition and
      metabolic disturbances and also during their lifetime, that could even be
      transmitted to the next generation(s). We highlight the susceptibility of
      epigenetic mechanisms controlling gene expression to environmental influences due
      to their inherent malleability, emphasizing the participation of transposable
      elements and the potential role of imprinted genes during critical time windows
      in epigenetic programming, from the very beginning of development, throughout
      life. Increasing our understanding on epigenetic patterns significance and their
      role in development, evolution and adaptation and on small molecules (nutrients,
      drugs) that reverse epigenetic (in)activation should provide us with the means to
      "unlock" silenced (enhanced) genes, and to "convert" the obsolete human thrifty
      genotype into a "squandering" phenotype.

PMID- 15959394
TI  - [How to prescribe physical activity in clinical practice?].
AB  - Accumulating scientific evidence indicates that regular physical activity confers
      significant health benefits. Besides its preventive interest, its promotion is an
      effective approach of several health problems, including obesity and type 2
      diabetes. Its clinical prescription is based on two complementary approaches
      aimed to decrease sedentary behaviours and/or to promote an active lifestyle with
      long-term objectives. Physicians can play a key role in motivating patients by
      advising them regarding their physical limitations, their goals, their concerns,
      and the barriers to exercise. Assessment of the patient's attitudes and
      motivation towards physical activity is a key element for the success.
      Objectives, clearly defined, should be evaluated and adapted on a regular basis,
      with the patient and taking into account the familial and social environment.

PMID- 15959395
TI  - [How to manage the metabolic syndrome?].
AB  - The metabolic syndrome represents the association in a single individual of a
      cluster of metabolic and hemodynamic factors, leading to an increased risk of
      type 2 diabetes and/or cardiovascular diseases. Several definitions exist (WHO,
      EGIR, NCEP-ATP III, AACE), but all of them include a cluster of criteria (hyper
      glycemia or type 2 diabetes, arterial hypertension, dyslipidemia, abdominal
      obesity) which increased these risks in parallel to their aggregation. The
      prevalence of the metabolic syndrome in industrialized countries represents 10 to
      30% of the adult population, depending on the definition used and of the range of
      age, with a regular progression, particularly in women. Thus, it is needed to
      identify subjects with metabolic syndrome in the general population, and not only
      in overweight/obese subjects. This review, briefly presents the main definitions,
      as well as current data on pathophysiology, prevalence and consequences of the
      metabolic syndrome. Steps to diagnose it and guidance for the therapeutic
      management of metabolic syndrome in primary care practice are described.

PMID- 15959396
TI  - [How to manage my patients' psychological disturbances?].
AB  - Psychological disturbances are frequently encountered in obese patients. The
      physician specialised in nutrition should take them into account within the
      therapeutic project and all along the patient's management. This review describe,
      according to the main obese patients' profiles (typology), the conditions for an
      optimal adequation between hopes and expectations from both the patient and the
      physician, as well as the psychiatrist role within the therapeutic project and
      during the management period.

PMID- 15959397
TI  - [What happens to the stomach after bariatric surgery?].
AB  - In France, indications for bariatric surgery are clearly defined in the
      recommendations issued by ANAES and medical societies. The number of surgical
      procedures performed in France, is currently estimated to be 10 to 12.000 per
      year, with a regular increase of the gastric banding technique, which represents
      now more than 75% of the procedures. This review presents the main surgical
      procedures, and particularly, insists on their post-operative complications and
      their prevention, diagnosis and management.

PMID- 15959398
TI  - [Editorial].

PMID- 15959399
TI  - [PPAR receptors: recent data].
AB  - The nuclear receptors PPAR (Peroxisome Proliferator-Activated Receptors) are
      transcription factors which form with the retinoid receptor RXR, a PPAR/RXR
      heterodimer, the functional transcription factor within cells. PPAR receptors are
      activated by their ligands, either naturals or synthetics, and modulate target
      gene transcription. There are three PPAR subtypes (PPARalpha, PPARbeta/delta et
      PPARgamma) coded by different genes, and two isoforms of PPARgamma proteins have
      been detected in humans (PPARgamma1 and PPARgamma2). PPAR are mainly modulators
      of lipid metabolism, but each receptor subtype is pharmacologically distinct, and
      development of synthetic PPAR agonists has shown their role in cellular (mainly
      adipocyte) differentiation and in glucose homeostasis. This review summarise the
      main data, currently available, on expression, biological functions, natural and
      synthetic (activators) ligands for the PPAR receptor subtypes. PPAR receptors key
      role in lipid and glucose metabolisms, has lead to a large clinical use of
      pharmacological agents acting as PPAR ligands: fibrates, PPARalpha agonists as
      hypolipidaemic treatment, thiazolidinediones (glitazones), PPARalpha agonists as
      antidiabetics. Lipid metabolism is impaired in insulin resistant skeletal
      muscles, fatty acids role in the pathophysiology of insulin resistance generates
      several hypothesis we briefly describe. Finally, we present and discuss
      experimental data, suggesting the activation of PPARbeta/delta in skeletal muscle
      to be a potential new approach in the treatment of insulin resistance and
      metabolic syndrome.

PMID- 15959400
TI  - [PPAR receptors and insulin sensitivity: new agonists in development].
AB  - Thiazolidinediones (or glitazones) are synthetic PPARgamma (Peroxisome
      Proliferator-Activated Receptors gamma) ligands with well recognized effects on
      glucose and lipid metabolism. The clinical use of these PPARgamma agonists in
      type 2 diabetic patients leads to an improved glycemic control and an inhanced
      insulin sensitivity, and at least in animal models, to a protective effect on
      pancreatic beta-cell function. However, they can produce adverse effects,
      generally mild or moderate, but some of them (mainly peripheral edema and weight
      gain) may conduct to treatment cessation. Several pharmacological classes are
      currently in pre-clinical or clinical development, with the objective to retain
      the beneficial metabolic properties of PPARgamma agonists, either alone or in
      association with the PPARalpha agonists (fibrates) benefit on lipid profile, but
      devoid of the side-effects on weight gain and fluid retention. These new
      pharmacological classes: partial PPARgamma agonists, PPARgamma antagonists, dual
      PPARalpha/PPARgamma agonists, pan PPARalpha/beta(delta)/gamma agonists, RXR
      receptor agonists (rexinoids), are presented in this review. Main results from in
      vitro cell experiments and animal model studies are discussed, as well as the few
      published short-term studies in type 2 diabetic patients.

PMID- 15959401
TI  - [Glitazones and pancreatic function].
AB  - Type 2 diabetes is characterized by two abnormalities, insulin resistance and
      insulin secretion defects. Their exact mechanisms and their interrelation are
      still a matter of debates. Development of hyperglycaemia in type 2 diabetes
      requires insulin secretion abnormalities. As the principal function of pancreatic
      beta-cell is insulin secretion, mainly in response to a glucose stimulus, it is
      of utmost importance to study abnormal beta-pancreatic function during the
      development of type 2 diabetes. The animal model of choice for such studies is
      the ZDF (Zucker Diabetic Fatty) rat. Two hypothesis are commonly discussed to
      explain the progressive beta-cell failure during type 2 diabetes evolution:
      glucotoxicity, mainly related to chronic hyperglycaemia effect on secretory beta
      cell function and to defective glucose utilization in skeletal muscles, and
      lipotoxicity, as a consequence of triglyceride accumulation in the islets of
      Langerhans. In fact, likely, these two phenomenons are linked together, this
      glucolipotoxicity leading to a cellular apoptosis, through mechanisms we
      describe. Thiazolidinediones (glitazones) are synthetic PPARgamma ligands. Their
      beneficial effect on glycaemic control in type 2 diabetic patients are well
      established. Several studies in ZDF rats, using rosiglitazone as a preventive
      diabetes treatment (early administration) or a curative one (starting
      administration when diabetes is well established), indicate, in this animal
      model, that rosiglitazone has a protective effect on pancreatic beta-cell and
      preserve its secretory function. These studies are described and discussed, as
      well as their practical implications.

PMID- 15959402
TI  - [Glitazones and atherosclerosis].
AB  - Atherosclerosis is a vascular disease, appearing early in life, and developing
      gradually and progressively, from the initial local inflammatory lesions, a stage
      at which endothelial dysfunction is already present, to the ultimate stage,
      culminating in atherosclerotic plaque rupture followed by thrombogenesis.
      Glitazones, specific agonists for the nuclear receptor PPARgamma, act at each
      stage of the atherogenesis process, and therefore are likely to convey
      cardioprotective activities in type 2 diabetic patients as well as in non
      diabetic patients at high cardiovascular risk (glucose intolerant subjects with
      or without associated metabolic syndrome). In this review, we summarize the main
      stages of atherosclerosis progression and their pathophysiological mechanisms,
      and the results of studies carried out with glitazones, either in in vitro
      experimental models or in vivo in various animal models, as well as results of
      recent studies in type 2 diabetic patients, which support the concept for a
      cardioprotective action of glitazones.

PMID- 15959403
TI  - [Metabolic syndrome: which definition(s) for which objective(s)?].
AB  - Several definitions are currently proposed to define metabolic syndrome (WHO,
      EGIR, NCEP-ATP III, AACE). The interest and the drawbacks of these definitions,
      as well as the "hypertriglyceridemic waist" phenotype proposed by Canadian
      authors, are described. All observational studies indicate an increased
      cardiovascular morbidity and mortality risk, and likely a type 2 diabetes
      increased risk, in individuals with metabolic syndrome. Therefore, it is
      justified to identify these individuals in order to implement preventive or
      therapeutic measures, and to be able to evaluate the intervention results. Use of
      any metabolic syndrome definition should be driven by the objective: either
      epidemiological studies, or clinical trials or assessment of intervention
      programs, or public health campaigns, or clinical management of at-risk
      individuals. The rationale for choosing one of these definitions is discussed on
      the basis of recent publications.

PMID- 15959404
TI  - [Glitazones clinical data: an update].
AB  - The thiazolidinediones (or glitazones) were recently added to the oral treatments
      for type 2 diabetes. Several recent studies, either in in vitro models or in
      animal models, lead to a better understanding of their mechanism of action.
      Recent, long term, controlled clinical studies, permit to define better their
      place and their condition of use (including adverse event prevention), as a
      monotherapy, or in association with metformin or a sulfonylurea when these drugs
      failed to achieve an optimal glycemic control. The beneficial metabolic effects
      of glitazones, generate great hopes for the prevention of the progressive beta
      pancreatic cell function decline observed in type 2 diabetics, and possibly to
      prevent and/or to delay type 2 diabetes in high at-risk subjects. This review
      describe and discuss the most recent studies and their results.

PMID- 15959405
TI  - [Coming clinical recommendations: where will the glitazones fit in?].
AB  - The recommendations for antidiabetic treatment in type 2 diabetes were published
      by AFSSAPS (Agence Francaise de Securite Sanitaire des Produits de Sante) in
      1999. These recommendations, as well as those published by ANAES (Agence
      Nationale d'Accreditation et d'Evaluation en Sante), indicate an optimal
      objective for ("good") glycemic control to be an HbA1c level< or =6,5%. These
      recommendations include two decision trees, according to body mass index (< 28
      kg/m2 or >28 kg/m2). Since their publications, our knowledge on diabetes
      pathophysiology and evolution from insulin resistance to type 2 diabetes, on the
      progressive decline of pancreatic beta-cell function, and on the close
      relationships between insulin resistance, type 2 diabetes and cardiovascular
      diseases, have increased and became more precise. Moreover, new approaches
      emerged, particularly the importance of the metabolic syndrome and the
      unfavorable role of visceral fat, when intervention studies (DPP, STOP-NIDDM)
      demonstrate the possibility to delay and/or to prevent type 2 diabetes. Finally,
      new oral antidiabetic agents (meteglinides and thiazolidinediones), as well as
      availability of long-acting insulin analogues, lead to the necessity to update
      current recommendations. This review, presents and discuss these various points,
      and the questions they generate, which have to be answer to update the
      therapeutic recommendations for type 2 diabetes.

PMID- 15959406
TI  - [Nonalcoholic steatohepatitis].
AB  - Nonalcoholic steatohepatitis (NASH) is a condition characterized by excessive
      deposition of fat in the liver (steatosis), inflammation and hepatocellular
      necrosis. While steatosis alone is generally a benign and stable condition, NASH
      can have a dire prognosis in a minority of patients, mainly because of fibrosis
      occurrence and progression to cirrhosis. Life-threatening complications such as
      liver failure and hepatocellular carcinoma have been described in NASH-induced
      cirrhosis. Insulin resistance is almost universally found in patients with NASH
      and the main risk factors for this condition are overweight and diabetes.
      Improvement in insulin sensitivity, whether achieved by diet, exercise and/or
      pharmacological interventions, results in a dramatic reduction of liver fat and
      inflammation and fibrosis as well. Therefore NASH should be viewed as the hepatic
      phenotypic manifestation of insulin resistance and a bona fide component of the
      metabolic syndrome. Liver injury should be assessed in diabetic and/or obese
      patients and the mechanisms by which insulin resistance promotes liver damage
      needs to be elucidated. The encouraging results of the use of PPARgamma agonists
      and, in particular, rosiglitazone, in human or experimental models of NASH,
      justifies future large-scale, randomized controlled trials.

PMID- 15959407
TI  - [Kidney and glitazones].
AB  - PPARgamma nuclear receptors are mainly expressed in adipose tissue. However, they
      are also expressed in renal glomerular tissue and in vascular walls, thus
      participating through various and complex mechanisms, to glomerular and vascular
      sclerosis and to nephropathy development and progression. Studies carried out
      with glitazones, pharmacological agonists of nuclear receptor PPARgamma, in
      experimental models, either in vitro, or in vivo in animal models, have
      demonstrated their favourable effects on arterial blood pressure and on
      prevention and/or progression of diabetic nephropathy. The few clinical studies
      conducted in type 2 diabetic patients to assess these effects, are also in favor
      of a beneficial effect of glitazones on blood pressure and nephropathy in these
      patients. Thus, it appears extremely important and fully justified to conduct
      specific studies in patients with type 2 diabetes, with the aim to establish and
      to better characterize these effects in various clinical conditions
      (antihypertensive effect in treated hypertensive patients according to the class
      of antihypertensive agents used, prevention of diabetic nephropathy and/or effect
      on its progression, renal protection, etc.). Some adverse events, although with a
      low incidence, may be associated with glitazone use (weight gain, peripheral
      oedema, fluid retention, etc.), and may limit their use in some patients. It is
      clearly important to better understand the pathophysiological mechanisms of these
      effects and their possible long term consequences. Finally, it is important to
      emphasize the easiness to use glitazones in patients with renal insufficiency,
      without the need to adjust the drug regimen.

PMID- 15959408
TI  - [Arterial wall and glitazones].
AB  - Numerous mechanisms contribute to impaired arterial wall in insulin resistant
      subjects and in type 2 diabetic patients. Endothelial dysfunction appears at an
      early stage of atherosclerosis progression, an accelerated process in diabetic
      patients. At a more advanced stage, arterial stiffness and thickening contribute
      to development of macroangiopathies. Inflammation plays a key role in these
      phenomena, particularly through growth factors and cytokines secretion in
      arterial wall cells. Thiazolidinediones, are pharmacological ligands of nuclear
      receptor PPARgamma and appear to act favorably on several pathophysiological
      mechanisms involved in these vascular dysfunctions and complications.
      Thiazolidinediones decrease plasma levels of C reactive protein, possess
      antiinflammatory effects through a reduction of inflammatory cytokines
      production, decrease free fatty acids levels, antagonize angiotensin II effects,
      increase adiponectin expression and production, etc. Pathophysiological
      mechanisms leading to vascular function impairment and their evaluation
      techniques are described, as well as the main thiazolidinediones beneficial
      effects on these mechanisms, which may lead to vascular prevention and/or
      protection in high cardiovascular risk insulin resistant and/or type 2 diabetic
      patients.

PMID- 15959409
TI  - Dimethoate effects on thyroid function in suckling rats.
AB  - The aim of our work is to study dimethoate effects on thyroid function given in
      drinking water (40 mg/kg body weight, equivalent to 0.2 g/L) to mothers from day
      zero until the 10th day after delivery. Pups and their mothers were sacrificed on
      day ten after parturition. Compared to a control group, dimethoate-treated pups
      showed a 48% decrease in body weight which could be attributed to a defect in
      thyroid hormones. Indeed, after treatment by dimethoate, plasma rates of free T4
      and T3 decreased by 56% and 40% in the young and by 27% and 15% in dams
      respectively. We can attribute the reduction in plasma thyroxine and
      triiodothyronine rates to a decrease in thyroid iodine levels (-75%) in the young
      and (-24%) in their mothers. The decrease in production of thyroid hormones after
      dimethoate treatment affect thyroid stimulating hormone (TSH) levels. In fact,
      plasma TSH levels were multiplied in dimethoate-treated group by factors of 2.31
      in dams and 1.96 in their offspring. These biochemical modifications confirmed
      the histological thyroid aspects of pups and dams. In fact, in dimethoate-treated
      rats, some thyroid follicles of pups presented vesicular cavities without
      colloid; others contained colloid. However in dams, thyroid follicles presented
      cubical epithelial cells which surrounded empty vesicular cavities.

PMID- 15959410
TI  - [Menopause in Africa].
AB  - Menopause occurs earlier in African women than European or American women.
      Multiple parity in a short period of time is the main reason. The myths and
      beliefs about this stage of life of the African woman are largely unknown.
      Symptoms do not vary greatly from those observed elsewhere, but social, economic
      and nutritional factors may influence the biological pattern. For some authors,
      the incidence of breast cancer does not decline at this age as it does in western
      countries. For other authors, 50% of breast cancers occur during the post
      menopause period, revealing an aggressive form of the disease. Exceptional
      uterine cancers have also been observed. Osteoporosis is apparently milder in
      African women. This observation should be examined in more detail.

PMID- 15959411
TI  - [Genetic hypophosphatemia: recent advances in physiopathogenic concept].
AB  - Renal proximal tubular reabsorption of phosphate and intestinal absorption both
      regulate phosphate homeostasis. Brush-border membrane Npt2a cotransporter is the
      key element in proximal tubular P (i) reabsorption. Inactivating mutations of
      Npt2a cause bone demineralisation and urolithiasis. An excess of a phosphaturic
      factor, called "Phosphatonin", could modulate phosphate reabsorption by
      inhibition on Npt2a. Inactivating mutation of PHEX, an endopeptidase-membrane
      coding gene, is responsible for X-linked Hypophosphatemia (XLH), because of an
      impaired degradation of phosphatonine by PHEX product. Autosomic Dominant
      Hypophosphatemic Rickets (ADHR) is explained by a mutation preventing FGF23 (one
      of the best identified phosphatonines) from cleavage. According recent data,
      FGF23, MEPE (Matrix Extracellular Phosphoglycoprotein) et FRP4 (frizzled related
      protein-4) are 3 putative "phosphatonines".

PMID- 15959412
TI  - Diabetes insipidus and panhypopituitarism revealing pituitary metastasis of small
      cell lung carcinoma: a case report.
AB  - Metastatic tumors of the pituitary gland are not commonly diagnosed during life
      in cancer patients. The occurrence of symptomatic lesions is also very unusual
      and difficult to differentiate clinically and radiologically from pituitary
      adenomas. We report a case of pituitary metastasis which was the prime
      manifestation of a small cell lung carcinoma in a 40-year-old man. This cancer
      was revealed by diabetes insipidus and a hypopituitarism.

PMID- 15959413
TI  - [Primary hyperparathyroidism revealed by pseudomyopathia].
AB  - We report the case of an 11-year-old child with delayed development who developed
      signs of exercise-induced pain in the lower limb muscles after an acute attack of
      appendicitis. He had difficulty standing up from the sitting position and
      ascending and descending stairs. The physical examination revealed increased
      reflex activity in the lower limbs. Initially, blood tests, MRI and EMG were
      normal. Serum phosphorus and calcium were not assayed. Eight months later, the
      boy's condition worsened (myopathy gait, hyperlordosis) leading to the possible
      diagnosis of muscle disease. After muscle biopsy, blood tests revealed
      hypercalcemia at 3.5 mmol/l (normal 2.2-2.6), hypercalciuria, and
      hypophosporemia. The diagnosis of primary hyperparathyroidism was confirmed by
      the abnormal level of parathormone initially (19 ng/ml) and later (156 ng/ml)
      with hypercalcemia. Medical treatment failed and surgery was performed to remove
      three and a half parathyroid glands. After removal, blood tests returned to
      normal in six days and the physical examination in three years. The diagnosis of
      principal cell hyperplasia was retained at the pathology examination. We found no
      evidence of hypercalcemia or other endocrinopathy such as multiple endocrine
      neoplasia (MEN 1 or 2a). Study of the menine gene did not reveal any mutation.
      Muscle dysfunction suggest possible abnormal phosphocalcium regulation. A normal
      parathormone level with hypercalcemia reveals inappropriate synthesis and
      secretion.

PMID- 15959415
TI  - An overview of the rationale for pharmacological strategies in type 2 diabetes:
      from the evidence to new perspectives.
AB  - Therapeutic strategies in type 2 diabetic patients should not only integrate both
      the targets and indications of the different therapies but should be also a
      compromise between the patient's and physician's goals and willingnesses. The
      rationale for therapeutic targets is based on recommendations that differ from
      one country to another. Even though HbA1c remains the "gold standard", monitoring
      of blood glucose at fasting and postprandial time-points is a complementary tool
      for estimating both the quality and safety of diabetic control. Despite the lack
      of available strong evidence-based data it seems that achieving glucose levels <
      130 mg/dl at fasting and < 180 mg/dl or < 140 mg/dl over postbreakfast or
      postlunch periods, respectively, might be a reasonable goal in most countries.
      The choice of appropriate strategies for treating type 2 diabetic patients should
      ideally be based on pathophysiological considerations. However for practical
      reasons, decisions for initiating or completing antidiabetic treatments are
      usually made by using such simple parameters as HbA1c and plasma glucose levels.
      The bridge between pathophysiological and clinical rationales can be obtained
      from the analysis of the relative contributions of fasting and postprandial
      glucose to the overall hyperglycaemia. In patients with HbA1c < 7.3%,
      postprandial glucose makes the major contribution to the overall hyperglycaemia,
      whereas the contribution of fasting glucose becomes progressively predominant in
      patients with HbA1c > 7.3%. As a consequence of these observations, initiation of
      antidiabetic treatments or implementation of second-line therapies should be
      aimed at reducing either postprandial excursions or fasting hyperglycaemia
      according to whether HbA1c levels are found respectively below or above a cut-off
      value of 7.3%.

PMID- 15959416
TI  - Homocysteine concentrations and vascular complications in patients with type 2
      diabetes.
AB  - OBJECTIVE: Hyperhomocysteinemia is a well known risk factor for the diseases of
      the cardiovascular system, which seem to be the main cause of increased mortality
      in patients with type 2 diabetes. The aim of the study was to evaluate the levels
      of homocysteine in patients with type 2 diabetes in respect to the regimen of
      diabetes treatment as well as the presence of diabetic complications. METHODS:
      The investigation was carried out in the group of 64 patients with type 2
      diabetes and in 18 healthy subjects from the control group. Clinical examination
      and measurements of homocysteine, folic acid, vitamin B12, glycosylated
      hemoglobin concentration and evaluation of parameters of the lipid metabolism,
      microalbuminuria and creatinine were done in both groups. RESULTS: Homocysteine
      concentration was significantly higher in the group of patients with diabetes in
      comparison to the control group (p = 0.0007). Diabetic patients had significantly
      lower concentrations of folic acid (p = 0.028) and HDL cholesterol (p = 0.025)
      together with higher levels of systolic blood pressure (p = 0.007). In the group
      of patients with diabetes no differences in homocysteine levels were found in
      respect to diabetes treatment. Diabetic patients with coronary artery disease had
      significantly higher homocysteine concentration in comparison to the group with
      diabetes without history of coronary artery disease (p = 0.0097). Homocysteine
      levels correlated significantly with incidence of ischaemic heart disease (r =
      0.44, p = 0.001) and microalbuminuria (r = 0.26, p = 0.019). Negative correlation
      was noticed in HDL concentrations (r = -0.30, p = 0.013) and the levels of folic
      acid (r = -0.30, p = 0.008). CONCLUSION: Our results suggest that
      hyperhomocysteinemia in diabetic patients may contribute to the development of
      chronic complications. The influence of diabetes treatment on Hcy levels requires
      further observations.

PMID- 15959417
TI  - The peroxisome proliferator activated receptorgamma2 (PPARgamma2) Pro12Ala
      variant: lack of association with type 2 diabetes in obese and non obese Tunisian
      patients.
AB  - OBJECTIVES: Peroxisome proliferator activated receptorgamma2 (PPARgamma2) is a
      nuclear receptor that regulates adipocyte differentiation, lipid metabolism and
      probably insulin sensitivity. There have been several reports on the relationship
      between the PPARgamma2 Pro12Ala genotype and the development of obesity or type 2
      diabetes. We designed a case-controlled study to investigate the potential
      association of the genetic variation of the PPARgamma2 gene with type 2 diabetes
      in Tunisians. METHODS: We used the polymerase chain reaction and restriction
      enzyme digestion to characterize the variation of the Pro12Ala polymorphism of
      the PPARgamma2 gene in 242 unrelated Tunisian patients with type 2 diabetes and
      246 healthy control subjects. RESULTS: Analysis of the Pro12Ala polymorphism of
      the PPARgamma2 gene in patients with type 2 diabetes and in control subjects
      revealed no significant differences in the PPARgamma2 allele frequencies between
      diabetic patients and control subjects. However the PPARgamma2 Ala12 allele was
      found significantly associated with a high level of systolic blood pressure in
      diabetic patients. Stratification of diabetic patients on obese and non obese
      subjects showed non significant differences in the PPARgamma2 Ala12 frequency
      between the two groups. CONCLUSION: These results suggest that the PPARgamma2
      gene is unlikely a major gene for type 2 diabetes mellitus or obesity in Tunisian
      subjects.

PMID- 15959418
TI  - Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of
      osteomyelitis in the diabetic foot.
AB  - OBJECTIVES: The diagnosis of osteomyelitis in patients with diabetic foot is
      difficult both clinically and radiologically. An early diagnosis is crucial to
      optimize therapeutic strategy. Among the diagnostic methods currently used,
      scintigraphy with ex-vivo labelled white blood cells is the gold standard, but
      cannot be performed in all centers; therefore 67Gallium citrate (67Ga) imaging in
      combination with a bone scintigraphy is still widely used. METHOD: The results of
      imaging 24 diabetic patients with 31 suspected osteomyelitic lesions using the
      antigranulocyte Fab' fragment (Sulesomab or LeukoScan or immunoscintigraphy) were
      prospectively compared with results from the bone scan coupled with 67Ga. The
      diagnosis of osteomyelitis was confirmed by either biopsy or follow-up,
      radiological imaging and clinical outcome. RESULTS AND CONCLUSION: Sulesomab
      correctly identified 12 of 18 osteomyelitic lesions while 67Ga was able to detect
      only 8 of 18. Therefore the sensitivity is 67% for Sulesomab and 44% for 67Ga.
      Among the 13 non-osteomyelitic lesions imaging with Sulesomab was able to rule
      out infection in 11 cases and 67Ga in 10 cases. The specificity is therefore 85%
      for Sulesomab and 77% for 67Ga. Image interpretation for Sulesomab in this group
      of patients is occasionally suboptimal when imaging is performed at 3 hours post
      injection. High vascular background in the early images may obscure infection
      especially in small bones. Practically, scintigraphy with Sulesomab is fast and
      simple due to ease of labeling, no ex-vivo handling of blood, low radiation and
      provides rapid diagnosis. The diagnosis of osteomyelitis obtained by the antibody
      fragment scintigraphy influences the management (guided biopsy) and therapy. In
      several patients, imaging with Sulesomab was able to rule out osteomyelitis,
      helping to avoid useless antibiotic therapy and its associated side effects.

PMID- 15959419
TI  - Stress myocardial scintigraphy and dobutamine echocardiography in the detection
      of coronary disease in asymptomatic patients with type 2 diabetes.
AB  - OBJECTIVE: The aims of this prospective study were: (1) to compare stress
      thallium-201 single photon emission computed tomography (SPECT) and dobutamine
      echocardiography (DE) in the detection of silent myocardial ischemia (SMI) in
      asymptomatic high risk diabetic patients; (2) to analyse long-term outcome after
      intensive care of SMI in these patients. METHODS: SPECT was performed in 100 high
      risk diabetic patients and DE in the first 75 patients. Coronary angiography was
      realized in patients with SMI, with revascularization for suitable lesions.
      Intensive treatment of atherosclerosis risk factors was performed in all
      patients. Patients were followed 2 +/- 0.5 years for the subsequent occurrence of
      cardiac death, myocardial infarction and revascularization. RESULTS: SMI was
      detected by SPECT in 62% and by DE in 10% of the patients (p < 0.0001), whereas
      significant coronary stenosis at angiography was detected by SPECT in 26% and by
      DE in 5% of the patients (p < 0.02). Independent predictive factors of
      significant coronary stenosis were male gender (p < 0.03) and peripheral arterial
      disease (p < 0.007). Nonfatal acute coronary syndrome occurred during follow-up
      in 2 patients (2%). Subsequent revascularization procedure was needed in 9
      patients. Baseline patients' characteristics, as well as SMI, were not predictive
      of cardiac event during follow up. CONCLUSION: SPECT seems more accurate than DE
      to detect significant coronary stenosis in high risk asymptomatic diabetic
      patients. In this population, aggressive treatment of SMI with systematic
      revascularization combined with intensive care of risk factors is associated with
      a favorable long-term prognosis, similar in diabetic patients with and without
      initial SMI.

PMID- 15959420
TI  - Blood glucose changes and adjustments of diet and insulin doses in type 1
      diabetic patients during scuba diving (for a change in French regulations).
AB  - OBJECTIVE: In France, diabetic subjects were not allowed to dive. The principal
      risk is hypoglycemia during immersion. However scuba diving is allowed in many
      countries. To follow blood glucose changes, food intake and insulin adjustments
      in type 1 diabetic patients when diving, and to propose specific guidelines for
      such patients willing to practice recreational scuba diving. METHODS: Fifteen
      well-controlled (mean HbA1c: 7.2%) type 1 diabetic patients without complications
      were volunteer to dive under strict medical monitoring. They dove 8 times in 4
      days in autumn at a depth of 20 meters, in 12 degrees C to 16 degrees C water. A
      strict protocol based on blood glucose was implemented to prevent hypoglycaemia.
      RESULTS: No case of hypoglycemia was observed and no faintness was reported
      underwater. Mean blood glucose before diving was 200 mg/dl (11 mmol/l). There was
      a mean fall in blood glucose of 40 mg/dl (2.2 mmol/l) during dives, a mean
      decrease in daily insulin doses by 19.3% on the last day. Daily energy intake was
      3,225 Kcal in average. A continuous glucose monitoring (CGMS) was performed in
      one patient and showed a rather stable glycemia during immersion but a decrease
      within the 8 hours after. CONCLUSION: When respecting a strict protocol to
      prevent hypoglycaemia, the risk of hypoglycaemia appears quite low. We recommend
      an ideal glycemic goal of 200-250 mg/dl (11-13.75 mmol/l) before immersion, a
      higher reduction of insulin doses (-30%) and taking carbohydrates on board in any
      case. The present data have recently led the French diving federation (FESSM) to
      allow type 1 diabetic patients to dive with some restrictive qualification
      requirements: dives within the "safety curve" (no decompression curve), in above
      14 degrees C water, depth limited to the median space range (6 to 20 meters),
      plus mandatory guidance by a diving instructor.

PMID- 15959421
TI  - Evaluation of a screening program for diabetic retinopathy in a primary care
      setting Dodia (Depistage ophtalmologique du diabete) study.
AB  - OBJECTIVES: The aim of this observational study was to evaluate the screening for
      diabetic retinopathy (DR) using eye fundus photography taken by a nonmydriatic
      camera and transmitted trough the Internet to an ophthalmological reading centre,
      as compared to a dilated eye examination performed by an ophthalmologist.
      METHODS: A total of 456 and 426 diabetic patients were included by two different
      groups of primary care physicians (PCPs), 358 being screened with the non
      mydriatic camera (experimental group) and 320 with dilated eye fundus exam
      (control group). RESULTS: The proportion of screened patients for whom PCPs
      received a screening report within the 6-month follow-up period was 74,1% for the
      experimental group and 71,5% for the control group. Screening for DR was negative
      in 77,6% of patients with eye fundus photographs vs 89,6% with dilated eye
      examination. DR was diagnosed in 62 patients (17,3%) with eye fundus photographs
      versus 31 with dilated eye examination (10,4%). Referral to an ophthalmologist
      was required in 59 reports of patients with photographs (16.5%), 23 of them due
      to high grade DR. Finally, the non-mydriatic camera was found of little
      inconvenience by patients. CONCLUSION: The telemedical approach to DR screening
      proved to be effective in providing primary care practitioners with information
      about their patient's eye status. This screening method allowed to identify
      patients requiring prompt referral to the ophthalmologist for further complete
      eye examination. In conclusion, this study provided successful results of DR
      screening using fundus photography in primary care patients, and strongly
      supports the need to further extend this screening program in a larger number of
      French sites.

PMID- 15959422
TI  - Cord serum insulin-like growth factor binding protein-1 and -3: effect of
      maternal diabetes and relationships to fetal growth.
AB  - OBJECTIVES: Insulin-like growth factor binding protein-1 and -3 (IGFBP-1 and -3)
      are the main insulin-like growth factor (IGF) carriers in fetal blood whose
      concentrations are regulated by hormonal factors such as insulin. IGFBPs may
      regulate fetal growth by altering the biological activity of IGF-I and IGF-II. We
      studied the effect of maternal diabetes on cord serum IGFBP-1 and IGFBP-3 levels,
      and the usability of IGFBP-1 and IGFBP-3 in the detection of birth weight
      variations. METHODS: Cord serum IGFBP-1 and IGFBP-3 concentrations were measured
      at birth by immunofluorometric assays in 67 pregnancies with type 1 diabetes and
      in 62 normal pregnancies. RESULTS: Concentrations of IGFBP-1 in cord serum were
      lower in diabetic pregnancies than in normal pregnancies (156 +/- 28 microg/l vs
      266 +/- 29 microg/l, P = 0.007), whereas those of IGFBP-3 did not differ
      significantly (3327 +/- 158 microg/l vs 2982 +/- 105 microg/l, P = 0.076). IGFBP
      1 correlated negatively and IGFBP-3 positively with birth weight z-score in
      diabetic pregnancies. The trend was similar in normal pregnancies. In multiple
      regression models, birth weight z-score was significantly associated with IGFBP-1
      in diabetic and normal pregnancies, and with IGFBP-3 in diabetic pregnancies.
      CONCLUSION: Maternal diabetes is associated with suppressed levels of IGFBP-1 in
      cord serum, whereas those of IGFBP-3 do not change markedly. In diabetic
      pregnancies, both cord serum IGFBP-1 and IGFBP-3 correlate with fetal growth.

PMID- 15959423
TI  - Albumin antioxidant capacity is modified by methylglyoxal.
AB  - OBJECTIVE: Oxidative stress seems to play a major role in diabetic vascular
      complication development. Plasma albumin, via its thiol groups, is the main
      extracellular antioxidant molecule. Methylglyoxal (MG) is a very reactive
      dicarbonyl compound increased in diabetes which strongly modifies proteins by non
      enzymatic glycosylation. The aim of this work was to study if MG could modify
      albumin antioxidant capacity. METHODS: Bovine serum albumin was incubated with 1
      mM MG at 37 degrees C for 7 days (MG-BSA). Albumin physico-chemical changes were
      evaluated by tryptophan autofluorescence measurement in the presence or in the
      absence of a quencher (acrylamide). Albumin antioxidant capacity was determined
      by thiol measurement using Ellman's reagent as well as in a cellular system (HeLa
      cells stressed by H2O2). RESULTS: MG-BSA exhibited important modifications as
      shown by conformational changes, decreased tryptophan autofluorescence (30%) and
      significant thiol loss (40%). MG-BSA led to important modifications resulting in
      oxidation and loss of albumin antioxidant capacity. MG-BSA modifications were
      close to the one observed in albumin isolated from diabetic patients. CONCLUSION:
      Our results suggest that deleterious effects induced by carbonyl stress in
      diabetes could also originate from a loss of albumin antioxidant capacity by
      dicarbonyl compound attack. The biological consequences of these findings have
      now to be investigated.

PMID- 15959424
TI  - Consumption of carbohydrate solutions enhances energy intake without increased
      body weight and impaired insulin action in rat skeletal muscles.
AB  - OBJECTIVES: In the present study, we investigated whether replacement of tap
      water by fructose or sucrose solutions affect rat body weight and insulin action
      in skeletal muscles. METHODS: Rats were fed standard rodent chow ad libitum with
      water, or water containing fructose (10.5% or 35%) or sucrose (10.5% or 35%) for
      11 weeks. Body weight and energy intake from chow and drinking solutions were
      measured. Urinary catecholamines secretion was determined after 50-60 days. At
      the end of the feeding period, soleus and epitrochlearis were removed for in
      vitro measurements of glucose uptake (with tracer amount of 2-[3H]-deoxy-D
      glucose) and PKB Ser473 phosphorylation (assessed by Western Blot) with or
      without insulin. RESULTS: Fructose and sucrose solutions enhanced daily energy
      intake by about 15% without increasing rat body weight. Secretion of urinary
      noradrenaline was higher in rats drinking a 35% sucrose solution than in rats
      drinking water. In the other groups, urinary noradrenaline secretion was similar
      to rats consuming water. Urinary adrenaline secretion was similar in all groups.
      Insulin-stimulated glucose uptake and insulin-stimulated PKB phosphorylation were
      not reduced by intake of fructose or sucrose solution. CONCLUSIONS: Fructose and
      sucrose solutions enhanced energy intake but did not increase body weight.
      Although noradrenaline may regulate body weight in rats drinking 35% sucrose
      solution, body weight seems to be regulated by other mechanisms. Intake of
      fructose or sucrose solution did not impair insulin-stimulated glucose uptake or
      signaling in skeletal muscles.

PMID- 15959426
TI  - Effects of micronized fenofibrate and vitamin E on in vitro oxidation of
      lipoproteins in patients with type 1 diabetes mellitus.
AB  - OBJECTIVE: The primary objective was to compare the antioxidant activity of
      micronised fenofibrate 200 mg to 400 IU of vitamin E and placebo, on the LDL and
      VLDL particles of patients with type 1 diabetes. The secondary objective was to
      investigate the possible synergy between micronized fenofibrate and vitamin E and
      to compare the efficacy of these treatments on lipids. METHODS: A double-blind,
      placebo-controlled trial in which patients were randomised into three treatment
      groups after a wash-out period of 8 weeks: the placebo group (Pla/Pla-group) in
      which patients received placebo during two consecutive periods of 8 weeks, the
      vitamin E group (Vit E/Vit E-group) in which patients received Vitamin E during
      two consecutive periods, and the fenofibrate/Vitamin E group (Fen/Fen + Vit E
      group) in which patients received fenofibrate during the first period, followed
      by fenofibrate and vitamin E during the consecutive period. Blood samples taken
      at each visit, were analysed for routine biochemistry, blood lipids and copper
      mediated lipid peroxidation in vitro. RESULTS: The lag time of the non-HDL
      lipoprotein oxidation increased in the group given fenofibrate. The lag-time
      increased further when fenofibrate and vitamin E were given in association. (This
      reached significance in the intention-to-treat population, P = 0.034). The AUC of
      TBARS formation in the Vit E/Vit E group decreased after the first period, but
      this effect was not enhanced by continuing vitamin E for another 8 weeks. The AUC
      of TBARS formation did not change significantly after the administration of
      fenofibrate. Only after the second period, when vit E was given in association,
      the AUC of TBARS formation decreased significantly (P = 0.004). Fenofibrate
      caused a significant decrease in total and LDL-cholesterol and triglycerides (P <
      0.05). In contrast, vitamin E had no effect on lipids. CONCLUSIONS: The
      combination of micronized fenofibrate 200 mg/day and vitamin E 400 IU/day tended
      to increase the resistance of non-HDL lipoproteins to copper-mediated oxidation,
      shown by a prolongation of the lag-time. Vitamin E administration only, decreased
      the oxidation of non-HDL lipoproteins shown by a reduction of TBARS formation.
      This protective effect of vitamin E tended to be amplified by micronized
      fenofibrate.

PMID- 15959425
TI  - Electronic pill-boxes in the evaluation of oral hypoglycemic agent compliance.
AB  - OBJECTIVE: To compare compliance in type 2 diabetic patients treated with
      glimepiride once daily or glibenclamide twice to three times daily. METHODS:
      Poorly controlled type 2 diabetic patients aged 35-65 years were randomized to
      glimepiride 1 mg once daily or to glibenclamide 1.25 mg twice daily. During
      initial titration, doses ranged from 1 to 6 mg once daily (glimepiride) and from
      1.25 mg twice daily to 5 mg 3 times daily (glibenclamide) to achieve fasting
      blood glucose < 126 mg/dL. The final titration phase doses were continued during
      the maintenance phase. Both treatments were packed in electronic pill-boxes
      fitted with a microprocessor to record dates and times of each opening.
      Compliance was assessed in terms of mean daily compliance (MDC) and the ratio of
      days with adequate compliance (DAC). Glycemic control was assessed in terms of
      the adjusted mean final HbA1c, and the incidence of hypoglycemia. Patient
      satisfaction was evaluated using the Diabetes Treatment Satisfaction
      Questionnaire. RESULTS: Compliance over the whole study was generally good, but
      the MDC was significantly better with glimepiride (87+/-16%) than with
      glibenclamide (80+/-17%;P < 0.0001). The ratios of DAC for glimepiride and
      glibenclamide were 87+/-16% and 67+/-24% respectively (P < 0.0001). The adjusted
      final HbA1c, and the incidence of hypoglycemia were similar in the two groups.
      Treatment satisfaction on the DTSQc was greater with glimepiride than with
      glibenclamide (P = 0.0034). CONCLUSIONS: Patient compliance and treatment
      satisfaction with once-daily glimepiride were significantly better than with
      glibenclamide 2 to 3 times daily.

PMID- 15959427
TI  - Markers for silent myocardial ischemia in diabetes. Are they helpful?
AB  - Silent myocardial ischemia (SMI) and silent coronary stenoses (CS) are two to
      seven times more frequent in diabetic patients than in non-diabetic patients. In
      addition to this, they have a higher predictive value for cardiovascular events
      than the classical cardiovascular risk factors, either taken alone or combined.
      Coronary arterial disease is the leading cause of mortality and morbidity in the
      diabetic population. Altogether, these data suggest that screening for SMI and
      silent CS is an important issue. We assume that detecting SMI and silent CS
      improves patient management, and leads to optimised follow-up, action taken on
      nutrition, exercise and lifestyle, management of the cardiovascular risk factors,
      and revascularisation procedures whenever possible. However, screening for SMI
      and silent CS is expensive and may induce morbidity. Selecting the patients with
      a high a priori risk of SMI and silent CS is therefore of major concern. Carotid
      or lower limb peripheral arterial disease, proteinuria, male gender, an age
      greater than 60 years, and two or more cardiovascular risk factors among smoking,
      microalbuminuria, dyslipidemia, hypertension, a family history of premature
      cardiac disease, and cardiac autonomic neuropathy have been demonstrated to be
      the best current predictors of SMI and silent CS. New markers, such as adhesion
      molecules, Lp(a), inflammation parameters or homocysteine, and endothelium
      function assessment might be of further help in the future.

PMID- 15959428
TI  - [Bowel obstruction: increasing collaboration between surgeon and radiologist].

PMID- 15959429
TI  - [Diffusion MR imaging of the central nervous system: clinical applications].
AB  - Diffusion-weighted MR imaging is a technique in which image contrast is
      determined by the motion of water molecules within tissues. This motion is
      characterized by the apparent diffusion coefficient (ADC). This technique is
      particularly useful for the early detection of cerebral infarction but many other
      diseases of the central nervous system are associated with a change in water
      diffusion and may be assessed by diffusion-weighted MR imaging. This is an easy
      and fast pulse sequence providing useful data for early diagnosis and prognosis
      as well as information about underlying pathophysiology. After an overview of the
      basic concepts of diffusion imaging and the knowledge required for image
      interpretation, we will assess the potential value of this technique for the
      diagnosis of the main diseases of the central nervous system.

PMID- 15959430
TI  - [Gastric ulcer].

PMID- 15959431
TI  - [Value of the small bowel feces sign at CT in adhesive small bowel obstruction].
AB  - PURPOSE: The purpose of this study is to describe the CT features of the small
      bowel feces sign and to determine its value as a positive criteria of non
      severity in adhesive small bowel obstruction. MATERIALS AND METHODS: We performed
      a retrospective study of adhesive small bowel obstructions diagnosed by CT from
      January 2001 to December 2002. All CT examinations featuring a small bowel feces
      sign were included. Clinical follow-up was available for all included patients.
      RESULTS: Twenty patients were included in this study. Twelve patients underwent
      successful conservative treatment with nasogastric aspiration. Urgent laparotomy
      performed in 6 cases and delayed surgical intervention performed in 3 did not
      show ischemic complication. Surgical management always consisted in lysis of
      adhesions without intestinal resection. CONCLUSION: Recently described in the
      radiological literature, the small bowel feces sign appears to be the first
      criteria of non-severity in adhesive small bowel obstruction.

PMID- 15959432
TI  - [Definition of a reproducible method for acetabular anteversion measurement at
      CT].
AB  - PURPOSE: To demonstrate the variability of acetabular anteversion angle
      measurement at CT and suggest a new and reproducible method of measurement.
      MATERIAL AND METHODS: Sawbone pelvis based study: We first realized a series of
      helical CT of the pelvis, with gradual increase in tilt angle, and measured
      acetabular anteversion angles on axial sections, then on sections parallel to the
      superior S1 endplate. Then, we made a series of radial sections centered at the
      acetabulum, and the anteversion angle was measured on each section. Finally, a
      test series of five in vivo pelvis was performed to evaluate the feasability of
      our method. RESULTS: The acetabular anteversion angle varies with pelvis tilt,
      whereas measurements obtained from sections parallel to the S1 endplate are
      constant. CONCLUSION: Acetabular anteversion angle should be measured from
      sections parallel to the S1 endplate, in order to minimize errors during total
      hip arthroplasties.

PMID- 15959434
TI  - [Multivisceral tuberculosis with aortic complication in an immunocompetent
      patient].
AB  - The medical and imaging data of a 59 year old male is reported. The patient
      presented with cough, fever, night sweats and weight loss, for which a final
      diagnosis of multivisceral tuberculosis (with peritoneal involvement and mycotic
      aneurysm) was made, by means of CT, MRI and laparoscopic findings. This disease
      is uncommon in developed countries with subjects lacking the usual risk factors.
      Because delayed treatment may be lethal, especially with such serious vascular
      complication, the authors review the value and limitations of CT and MRI along
      with the suggestive features.

PMID- 15959433
TI  - [Imaging of pulmonary hydatid cyst in children].
AB  - PURPOSE: We present the various imaging features of pediatric pulmonary
      hydatidosis based upon a series of 232 cases. The importance of chest radiographs
      and thoraco-abdominal ultrasound is emphasized. PATIENTS AND METHODS: A
      retrospective study of 232 children with pulmonary hydatidosis is presented. The
      232 cases (130 boys and 102 girls, age range: 18 months to 14 years) were studied
      between January 1982 and December 2001. Chest radiographs were available in all
      cases, chest ultrasound in 156 cases and abdominal ultrasound in 212 cases. CT
      was only performed in 40 cases. Surgery was performed for all patients. Diagnosis
      was confirmed with serology tests and/or pathological study of resected cysts.
      RESULT: The total number of pulmonary cysts detected on chest radiographs was
      344. The right lung was more frequently affected than the left (208 lesions). A
      simple cyst was the most commonly observed lesion (220 cysts). Complicated forms
      were noted in 118 cases. 180 cysts were observed at ultrasound. A simple cyst
      presenting as an anechoic mass was noted in 140 cases. In 38 cases, the lesion
      was heterogeneous. In two lesions endocystic germinal membranes were detected. CT
      visualized 50 lesions. Thirty three lesions were complicated with endocystic
      floating or collapsed membranes. Bronchiectasis was observed in seven cases.
      CONCLUSION: Chest radiographs and thoraco-abdominal ultrasound are very useful
      for the diagnosis of pulmonary hydatidosis and evaluation of lesion extension. CT
      is useful for diagnosis of atypical or complicated lesions and to detect
      bronchiectasis.

PMID- 15959435
TI  - [Periosteal hemangioma of the distal humeral: case report and review of the
      literature].
AB  - The authors report a case of periosteal cavernous hemangioma of the distal
      humeral. They describe the imaging findings of hemangiomas of long tubular bones
      and discuss their differential diagnosis.

PMID- 15959436
TI  - [Telangiectatic osteosarcoma of the scapula: a case report].
AB  - Telangiectatic osteosarcoma is a rare entity and rarely involves flat bones. The
      authors report the case of a 4 year old child, with a four month history of
      progressive left shoulder swelling. Radiographs and CT of the left shoulder
      revealed a large lytic lesion with cystic areas of the scapula, simulating the
      appearance of an aneurysmal bone cyst. Surgical biopsy was performed and showed
      telangiectatic osteosarcoma.

PMID- 15959437
TI  - [Hydatid cyst of soft tissues: MR imaging findings (Report of three cases)].
AB  - Three cases of hydatid disease of the soft tissues are reported. All presented as
      soft tissue lesions in the neck and lower extremities. All three cases were
      studied with ultrasound (US) and magnetic resonance (MR) imaging techniques. Two
      patients presented with multivesicular lesions, which were considered diagnostic
      for hydatid disease. The third showed a lesion with hypoechoic solid and
      lobulated pattern mimicking lymph node. MR outlined the cystic pattern with
      intense peripheral enhancement and was suggestive of an infected cystic lesion.
      Surgery was performed in all three cases. Hydatid disease presenting in the soft
      tissues can be diagnosed with confidence, when US and/or MR shows multivesicular
      lesions. MR appears to be the most useful imaging technique when a complex or
      solid pattern is present. Enhancement of the peri-cystic soft tissues can be
      considered as a suggestive MR feature of soft tissue hydatid disease.

PMID- 15959438
TI  - [What is your diagnosis?].

PMID- 15959439
TI  - [Adjustment disorders in oncology: a conceptual framework to be refined].
AB  - The use of stringent sets of diagnostic criteria often represents a daily
      clinical challenge for mental health professionals caring for cancer patients.
      Many nosological classification systems were not specifically developed to meet
      the peculiarities associated with the emotional experience of cancer. In
      particular, the diagnosis of adjustment disorder according to the Diagnostic and
      Statistical Manual of mental disorders appears inappropriate in this context. It
      is questionable, indeed, how to assess the "excessive" nature of psychological
      distress ari-sing in response to such a burdening event as a cancer diagnosis.
      Furthermore, the conceptual validity of the adjustment disorder construct may be
      of poor clinical relevance in patients suffering from a life-threatening medical
      condition and its widespread consequences. In this paper, we intend to offer an
      operational definition of adjustment and we argue that a vast majority of cancer
      patients currently receiving a diagnosis of adjustment disorder actually suffer
      from either subthreshold depression or from full or partial presentation of post
      traumatic stress disorder. We first briefly review some available models of
      psychological adaptation. We also argue that trying to explain the experience of
      cancer alongside a continuum of psychological distress does not help us to better
      understand underlying adjustment processes and to treat emotional disturbances
      more effectively. The literature is currently scanty about the critical role of a
      psychological trauma, namely the diagnosis of cancer, in generating emotional,
      cognitive and behavioral responses. The very fact that an average of 10% of
      cancer patients have been shown to meet criteria for PTSD might suggest that the
      existence of a specific trauma stress adaptation process in this particular
      patient population. The confirmation of these hypotheses by clinical observation,
      experimental psychology paradigms or functional brain imagery studies could have
      substantial implications for the treatment of psychological distress in patients
      with cancer. Issues such as the relevance of pharmacological treatment of
      subthreshold depression--which has received little attention in the general
      literature--or the role of psychodynamic approaches in the management of cancer
      related traumatic dimensions, should be addressed systematically.

PMID- 15959440
TI  - [Patient and their relatives' satisfaction regarding a home-based crisis
      intervention provided by a mobile crisis team].
AB  - The goal of this survey was to evaluate the patients and their relatives'
      satisfaction with a home-based crisis intervention provided by a psychiatric
      mobile crisis team (Equipe Rapide d'Intervention de Crise, hopital Charcot,
      Plaisir). We were particularly interested in measuring satisfaction with
      telephone response time, team mobility, patient welcome, family consultations,
      information given to patients and the number of caregivers. We designed a
      questionnaire that included 24 closed questions and 2 open-ended questions.
      Replies were collected over the telephone by an outside psychologist with no
      prior knowledge of the patients. The inclusion criteria were the following: the
      patient had to have received a home-based crisis intervention from the mobile
      crisis team and to have received at least two follow-up consultations. The
      response rate was 95%, from 81 relatives and 73 patients. The results show a high
      level of overall satisfaction, with satisfaction levels at over 90% for some of
      the questions. High satisfaction was due to the human and professional approach
      of staff - their listening skills and competence - the 24-hour availability of
      the telephone service, the fast intervention of the team, the team mobility, and
      the systematic involvement of relatives as part of the program. Low satisfaction
      was due to the high number of caregivers, the short length of programs, the
      patient referral process to outpatient services, the lack of information on
      medication and patients' illness and the sad appearance of the building. These
      results lead us to improve some aspects of our service or at least to explain our
      services more fully to clients. More generally, these results encourage us to
      listen more attentively to patients' opinions on how they experience their
      psychiatric care.

PMID- 15959441
TI  - [A study of the psychometric properties of the Icelandic translation of Obsessive
      Thoughts Checklist (OTC) with confirmatory factor analysis].
AB  - The Obsessive Thoughts Checklist (OTC) differs from several other measures of
      obsessive-compulsive symptoms in its focus on obsessive thoughts instead of
      compulsive behaviour. The OTC has been used in several studies in France and
      abroad and support for the discriminant and convergent validity of the instrument
      has been gathered. The authors of the OTC recently reported 3 underlying factors
      in this instrument: a perfectionism/verification factor, a contamination factor
      and a responsibility factor. In an earlier study of the OTC a 2 factor solution
      was however suggested. It therefore seems important to further elucidate the
      factorial structure of this instrument using confirmatory factor analysis. In
      this study data on the Icelandic translation of the OTC from three samples of
      Icelandic college students were submitted first to an exploratory and then to a
      confirmatory factor analysis. The total number of subjects was 614 college
      students, 254 men and 360 women with a mean age of 24.4 (sd = 5.0). The results
      of the exploratory factor analysis (PCA) submitted to a varimax rotation are
      presented in table I. The 3 expected factors were reproduced with few cross
      loadings. In the confirmatory factor analysis the fit of three models to the data
      were evaluated: a 1 factor model, the 2 factor model of Bouvard et al. and the 3
      factor model of Bouvard et al.. An initial examination of the data led to
      logarithmic transformation of 18 items to reduce skewness in their distributions.
      The data was subsequently subjected to a confirmatory factor analysis to compare
      the three-factor model with the two-factor and one-factor models for the OTC. The
      factors for the three- and two-factor models were allowed to correlate freely.
      The data were analysed using the EQS procedure, and the models tested were
      covariance structure models. Table II presents the goodness of fit indices for
      all three models. The results show that none of the three models provide an
      overall appropriate fit for the data. However, the fit indices for the three
      factor model were considerably higher than found for the two or one factor models
      and the RMSEA index for the three-factor model suggested an acceptable fit for
      that model. Although the three-factor model suggests the best fit of all three
      models, the fit indices were still unacceptably low. Further examination of the
      data revealed a pattern of standardized residuals suggesting that this might in
      part be attributable to three items from the responsibility factor (items 26, 19
      and 15) not being well specified within the model. When the residuals for these
      items were allowed to correlate, the fit of the model was substantially improved
      (CFI = 0.85; GFI = 0.87; AGFI = 0.85; RMSEA = 0.062). This indicates that a
      revision of the responsibility scale might be appropriate. Table III provides the
      means, standard deviations and the alpha coefficients for the 3 subscales of the
      OTC as well as for the total scale. In one subsample of the study (sample 1, n =
      169) the OTC was administered together with the Padua Inventory-Washington State
      Revision (PI-WSUR) measuring obsessive-compulsive symptoms, the Penn State Worry
      Questionnaire (PSWQ) and the Community Epidemiological Scale-Depression (CES-D)
      measuring depression. In order to investigate the convergent validity and
      divergent of the OTC its correlation with the PI-WSUR was compared with its
      correlations with PSWQ and CES-D. These correlations shown in table IV support
      the convergent and divergent validity of the OTC. In another subsample of the
      study (sample 2, n = 296) the OTC was administered together with the Maudsley
      Obsessive Compulsive Inventory (MOCI). For samples 1 and 2, zero order and
      partial correlations were calculated between the subscales of the OTC and the
      subscales of the other instruments. As shown in table V the strongest
      correlations between the checking/perfectionism and the contamination subscales
      of the OTC were with corresponding subscales of the PI-WSUR and the MOCI. It is
      concluded that the factorial, the convergent and the divergent validities of the
      Icelandic translation of the OTC are supported in a student population even
      though the somewhat suboptimal fit of the three-factor model may indicate that a
      revision of the responsibility factor might be in order. This should however be
      further studied in a clinical population.

PMID- 15959442
TI  - [Comorbidity between eating disorders and anxiety disorders: results].
AB  - Taking into account the methodological problems underlined in the first part of
      this paper, the current review aims to answer three questions: 1) Is there
      convincing evidence that anxiety disorders (AD) are more frequent among women
      with eating disorders (ED) than among women from the community? 2) Is there
      convincing evidence that prevalence of AD differs across diagnostic types or
      subtypes of ED? 3) What is the chronology of appearance of the two disorders? We
      performed a manual and computerized search (Medline) for all published studies on
      comorbidity between ED and AD (1985-2002 period), and selected the most relevant
      studies. An increased risk for AD in subjects with ED has been shown in several
      community studies, but studies conducted in referred subjects have led to
      inconstant findings. The answer to the questions remains uncertain, because too
      few studies included control groups and few studies have compared diagnostic
      subgroups of ED subjects, with scarce or conflicting results.

PMID- 15959443
TI  - [Validation of the French version of the Body Shape Questionnaire].
AB  - In today's societies, pressures from the idea of thinness are omnipresent and
      lead to a corporal dissatisfaction with an excessive preoccupation of the body's
      image. It seems important to have, in France, a device that can evaluate the
      corporal dissatisfaction degree, for the reason that the troubles of the body's
      image is a common diagnostical category to the anorexia and bulimia (DSM IV,
      1994). Cooper et al. (1987) have developed one-dimensional questionnaire of 34
      items in order to measure the worries towards the weight and the shape of the
      body, called the "Body Shape Questionnaire" (BSQ). Its concurrent validity has
      been shown with the using of the corporal dissatisfaction under-scale of the
      Eating Disorders Inventory (EDI; Garner et Olmsted, 1984) and the using of the
      diagnostical questionnaire: Eating Attitude Test (EAT; Garner et Garfinkel,
      1979). The BSQ gives us a way to explore the role of extreme worries towards the
      body's apparence in the development, the keeping and the treatment of eating
      disorders. From this point the BSQ is a tool widely used on an international
      level in researches on the eating disorders. It has been validited in Spain and
      in Germany whereas it has not been yet subject to a validation in France. For
      this reason, we proposed to use the BSQ on the french population. METHODOLOGY:
      The sample is made of 242 university girl students. The average age is 20.7 years
      old with an standard deviation of 2.26. The size and the weight helped us to
      calculate the Body Mass Index (BMI) which is in fact the weight divided by the
      size squared. The average BMI is 21.06 kg/m2 +/- 2.87. Regarding the evaluating
      devices, the BSQ is presented as a scale of 34 items marked by 6 different
      points: 1 never, 2 barely, 3 sometimes, 4 often, 5 very often, 6 always. After
      getting the authorization form the authors to respect during these kinds of
      procedures, we have started validation. The corporal dissatisfaction under-scale
      of Eating Disorder Inventory (EDI, Garner et al., 1991) is made of 9 items and
      has a scale of 6 points going from "never" to "always". In order to evaluate the
      accuracy of the Body Shape Questionnaire (BSQ) in France, we made a test/retest.
      The concurrent validity of the BSQ has been evaluated by the EDI. The 242
      subjects have been asked to fill in both questionnaires during the test and the
      re-test (4 weeks after the test). We have evaluated the accuracy of the BSQ with
      the calculation of the constancy test/retest (Pearson's r) and the measure of the
      internal consistency (Cronbach's alpha). Then, we tested the validity regarding
      an external criteria. The validation procedure is based here on an examination of
      the correlations between the tests results (BSQ) and another measure taken as
      criteria (EDI). The solutions proposed by the factorial exploratory analysis have
      been tested by confirmatory analysis using the 2 index of adjustment: the GFI
      ("Goodness of Fit Index") and the CFI (Comparative Index of Bentler) which,
      greater than 0.85, shows a satisfying adjustment and the RMC (redidue) which has
      to be less than 0.10 for a satisfying adjustment. Finally, inferential
      statistical analysis have studied the relations between the weight's category and
      the total result at the BSQ and the results of the factors sprung from factorial
      analysis. RESULTS: Correlations between the items of test/re-test BSQ are greater
      than 0.93. The alpha coefficient is high for the test (0.95) and also for the re
      test (0.94). This shows a very good internal consistency between the 34 items of
      the BSQ. Concerning the EDI, the correlation between the test/re-test are greater
      than 0.98. The alpha coefficient of Cronbach is high: 0.85 for the test and 0.84
      for the re-test. The Pearson's r of the BSQ/EDI test and the BSQ/EDI re-test
      greater than 0.7 point out the concomitant validity of the BSQ with the EDI. We
      made a factorial analysis of the BSQ (test) on the 242 subjects. We used the
      extraction of the main components method with the extraction's rule of the curve
      for the real values. The transformation method used here is the normalised
      Varimax. The factorial analysis shows four factors with their own value greater
      or equal to 1 (15.1; 1.77; 1.48; 1.08). This solution concerning these four
      factors explains 55.2% of the total variance. The oblical rotations analysis of
      the four factors seems to point out a high correlation between these latters
      (from 0.54 to 0.77), this suggests a hierarchical pattern with a single factor
      which is confirmed with an Cronbach's alpha of 0.95. Then, we chose to gather
      around each selected factors the items presenting a substantial saturation,
      greater than or equal to 0.5 and which are saturated by only one factor. The
      first factor obtained by the factorial analysis of the BSQ has been called
      "social avoidance and shame of the exposure of the body". The internal coherence
      of this factor is satisfactory (Cronbach's alpha = 0.87). The second factor
      obtained has been called "body dissatisfaction compared to the lower parts ot the
      body (Cronbach's alpha = 0.90). The third factor has been called "using laxatives
      and vomiting in order to reduce body dissatisfaction" The fourth factor has been
      called "unsuited cognitions and behaviours in order to control the weight
      (Cronbach's alpha = 0.76). The solution with 1 and 4 factors has been tested by a
      confirmatory analysis. The adjustment parameters of the unifactorial pattern were
      not satisfactory (GFI = 0.76, CFI = 0.83, RMC = 0.5). The 4 factors pattern
      adjusted better to the data (GFI = 0.86, CFI = 0.90, RMC = 0.5). In order to
      determinate the differences between the weight/score categories to the BSQ) score
      in comparison to the 4 factors (coming from the factorial analysis), several
      Anova have been released as well as post-hoc tests (test of Sheffe). There is a
      significant effect of the weight category on the corporal dissatisfaction (BSQ
      result), F (2.230) = 11.34; p < 0.0001. Scheffe's test placed in a prominent
      position the fact that the subjects having an overweight (99.85 +/- 31.34) have a
      corporal dissatisfaction significantly greater than the subjects having a normal
      weight (74.08 +/- 27.94) and presenting a thinness (63.19 +/- 23.61). We pointed
      out a significant effect of the weight category on factor one "social avoidance
      and shame of the exposure of the body" [F (2.232) = 20.18; p < 0.001], on factor
      2 "body dissatisfaction compared to the lower parts of the body" [F (2.232) =
      6.38; p < 0.005] and factor 4 "reduce body dissatisfaction and unsuited
      cognitions and behaviours in order to control the weight" [F (2.232) = 5.67; p <
      0.005]. However, there is no effect in the weight category for factor 3 "using
      laxatives and cominting in order to reduce the corporal dissatisfaction" [F
      (2.232) = 5.67; p > 0.05]. Sheffe's test highlighted the fact that the subjects
      having overweight have a result more important than the ones having a normal
      weight and presenting a thinness for factor 1.2 and 4. DISCUSSION: The BSQ
      "French version" seems in fact to present the same metrical qualities than its
      original Anglo-Saxon and Spanish versions. The concluding results invite us to
      continue our study of the BSQ including in our patients, the bulimic subjects and
      the ones who are worried about corporal aspect. Its implications on the clinical
      field could be really interesting especially on people suffering from the eating
      disorders. Then, the BSQ could provide us a way to explore the role of an extreme
      worry of the body's appearance in the development, the maintenance and the
      treatment of the eating disorders.

PMID- 15959444
TI  - [Patients with a complete or partial remission of Major Depressive Episode as
      part of Recurrent Major Depressive Disorder: description of ECLAIR study
      population].
AB  - Some guidelines and expert consensus consider the way of care management
      practices for the recurrent depressive disorder, particularly according to
      different identified risk factors for recurrence. But, few data are available
      about the way that these risk factors influence the care management of depressive
      recurrent patients during the partial or complete remission phase. Eclair study
      is a longitudinal observatory multicentric and national study, which describes
      the different risk factors that influence the psychiatrist decision about the
      following of patients suffering form Major Depressive Disorder (at least 3 Major
      Depressive Episode (MDE) according to DSM IV). This article presents the
      inclusion data (V0) of patients, with a focus on their demography characteristics
      and history of trouble, diagnosis, symptomatology evaluation (with CGI-S, HAM-D,
      Carroll scale and Sheehan scale) and Cloninger's personality questionnaire (TCI).
      A total of 596 patients with a recurrent depression either on partial remission
      (PaR) or complete remission (ToR) to their last episode at the selection, have
      been included. Complete remission was defined by the presence of a maximum of two
      criteria of MDE (according to DSM IV) excepted depressed mood and diminished
      interest or pleasure during at least two months with a HAM-D (17 items) score < 7
      and partial remission was defined by the persistence of depressed symptoms but
      not sufficient to complete a diagnosis of MDE (according to DSM IV) associated
      with a HAM-D (17 items) score between 8 and 13 included. Mean HAM-D scores at V0
      were 10.3 +/- 1.6 for PaR group and 4.0 +/- 1.9 for the ToR group. Free time
      since last episode was 6.5 +/- 10.5 months in ToR group and 11.2 +/- 16.9 months
      in PaR group (n = 385). Residual symptomatology between prior episodes was
      systematically present for 47.6% patients in PaR group, and for 26.7% patients
      ToR group. The feel to have a stressful daily life persisted for 62.5% of patient
      in PaR group and 34.3% in ToR group; 70.3% patients in PaR group and 57.9%
      patients in ToR group reported persistence of causal factor. The main collected
      risk factors for recurrence were the number of prior depressive episodes (64.9%),
      familial conflict existence (52.9%) and recent events of life (45.1%). In the
      TCI, a significant difference in comparison with the French normative data has
      been found for 3 dimensions: Harm Avoidance, Cooperativeness and Self
      Directedness. Some differences were obtained for Novelty Seeking, Reward
      Dependence, and Self-Transcendence, but without sufficient clinical
      significance.This study confirms various characteristics about the unipolar
      depressive disorder, particularly the high risk of recurrence in patients with
      high number of previous episodes. In the research of predictive depressive
      recurrence signs, it would be interesting to focus on discriminating elements
      between complete remitted patients and partial remitted patients.

PMID- 15959445
TI  - [Prevalence and comorbidity of psychiatric disorders in the French general
      population].
AB  - INTRODUCTION: ESEMeD is the first international epidemiological study using a
      random sampling method that has allowed the prevalence of psychiatric disorders
      in France to be measured with precision and compared directly with that observed
      in other European countries. OBJECTIVES: 1) To determine the 12 month and
      lifetime prevalence of mood -disorders, anxiety disorders and alcohol-related
      disorders. 2) To estimate the comorbidity between these disorders. 3) To evaluate
      potential demographic risk factors for these disorders. METHODS: This was a
      transversal survey carried out between 2001 and 2003 of non-institutionalised
      subjects aged 18 or over in the general population of Germany (n = 3,555),
      Belgium (n = 2,419), Spain (n = 5,473), France (n = 2,894), the Netherlands (n =
      2,372) and Italy (n = 4,712). In France, the sampling source was a randomly
      generated list of telephone numbers. Subjects were interviewed at home by
      professional interviewers. The WMH-CIDI questionnaire was used. RESULTS: The
      participation rate was 46% for France and 61% for all six countries combined. The
      12 month and lifetime prevalence rates observed were respectively 6.0% and 21,4%
      for major depressive episodes, 1.6% and 7.9% for dysthymia, 2.1% and 6.0% for the
      generalised -anxiety disorders, 1.2% and 3.0% for panic disorders, 0.6% and 1.8%
      for agoraphobia, 2.2% and 3.9% for post-traumatic stress disorder, 1.7% and 4.7%
      for social phobia, 4.7% and 11,6% for specific phobia, 0.5% and 4.1% for alcohol
      abuse and 0.3% and 1.6% for alcohol dependence. Mood disorders and anxiety
      disorders were significantly more frequent in women, whilst alcohol-related
      disorders were more frequent in men. The prevalence of all three types of
      disorder was lower in elderly subjects and in those living in a rural
      environment. Mood disorders and alcohol-related disorders were more frequent in
      individuals living alone and mood disorders more frequent in those without paid
      employment. 38% of subjects with mood disorder also presented an anxiety disorder
      or an alcohol-related disorder. The comorbidity of mood and anxiety disorders was
      more frequent in women, younger subjects and those living alone. The comorbidity
      rate in subjects with anxiety disorders was 26% and did not differ between
      genders. For alcohol-related disorders, there was a striking difference in
      comorbidity rate between men and women: 26% in the former and 67% in the latter.
      CONCLUSION: This study underlines the high prevalence of mood disorders, anxiety
      disorders and alcohol-related disorders in France and demonstrates a high degree
      of comorbidity between them. For this reason, it is important to evaluate and
      take into account potential comorbidity in the management of individuals with
      psychiatric disorders.

PMID- 15959446
TI  - [Psychotropic drug use and mental psychiatric disorders in France; results of the
      general population ESEMeD/MHEDEA 2000 epidemiological study].
AB  - INTRODUCTION: The use of psychotropic drugs is high in France and has increased
      over the last two decades. To date, no national study evaluating psychotropic
      drug use in the context of the diagnosis of psychiatric disorders has been
      performed. Such data has now been generated in the ESEMeD/MHEDEA 2000 study,
      which has allowed comparison of the situation in France with that in five other
      European countries (Germany, Belgium, Spain, the Netherlands and Italy).
      OBJECTIVES: 1) To describe the declared use of psychotropic drugs (globally and
      by therapeutic class) in order to evaluate annual prevalence, treatment duration
      and demographic factors associated with use. 2) To estimate the proportion of
      subjects with an anxiety disorder, mood disorder or alcohol-related disorder
      (abuse or dependence) that have been appropriately treated with an antidepressant
      or anxiolytic drug. 3) to evaluate the proportion of psychotropic drug users who
      fulfil diagnostic criteria for these three classes of psychiatric disorder.
      METHODS: This was a transversal survey carried out between 2001 and 2003 of non
      institutionalised subjects aged 18 or over in the general population of Germany
      (n = 3,555), Belgium (n = 2,419), Spain (n = 5,473), France (n = 2,894), the
      Netherlands (n = 2,372) and Italy (n = 4,712). In France, the sampling source
      used was a randomly generated list of telephone numbers. Subjects were
      interviewed at home by professional interviewers. The WMH-CIDI questionnaire was
      used. RESULTS: In France, 21% of subjects interviewed (n = 580) had taken at
      least one psychotropic drug during the year. For 19%, this was an anxiolytic or
      hypnotic (AX-HY), for 6.0% an antidepressant (AD), for 0.8% an antipsychotic (AP)
      and for 0.4% a mood regulating drug (TY). The distribution of users of AX-HY
      according to treatment duration was the following: 44% (1 to 15 days), 13% (16 to
      30 days), 14% (1 to 3 months), 6.7% (3 to 6 months) and 23% (> 6 months). For
      users of ADs, the distribution was: 21% (1 to 15 days), 7.8% (16 to 30 days), 18%
      (1 to 3 months), 12% (3 to 6 months) and 42% (> 6 months). For subjects
      fulfilling diagnostic criteria for a mood disorder in the previous year or over
      their lifetime, 43% and 29% respectively had taken an AX-HY in the last twelve
      months and 29% and 16% an AD. For those who fulfilled diagnostic criteria for an
      anxiety disorder in the previous year or over their lifetime, the use of an AX
      HY, in the last twelve months, concerned 43% and 30% of subjects respectively,
      whilst that of AD concerned 16% and 14%. For previous year or lifetime alcohol
      related disorders, AX-HY use, in the last twelve months, concerned 63% and 22% of
      subjects respectively and use of ADs 9.3% and 7.2%. Amongst users of AX-HY in the
      last twelve months, a previous year or lifetime diagnosis of mood disorders was
      made for 16% and 39% of subjects respectively. Amongst users of ADs, the
      respective prevalence was 31% and 64%. A twelve-month and lifetime diagnosis of
      anxiety disorders was identified in 22% and 37% of users of AX-HY and among 27%
      and 50% of users of AD respectively. A twelve-month and lifetime diagnosis of
      alcohol-related disorders was found in 2.5% and 6.6% of users of AX-HY and among
      1.1% and 7.8% of users of AD respectively. 68% of users of AX-HY had fulfilled
      none of these diagnostic criteria in the previous 12 months and 46% had never
      fulfilled them in their lifetime. With respect to AD users, the proportion who
      did not meet these diagnostic criteria in the previous 12 months was 56%,
      compared to 20% over their lifetime. Comparison of the French data from the study
      with those of the entire European sample showed that the annual prevalence of AX
      HY and AD use was higher in France with mean treatment durations that were
      shorter. For antipsychotics and mood regulators, no clear differences were
      observed between France and the six countries of the study taken together.
      DISCUSSION: Over the last two decades, use of AX-HY seems to have decreased in
      France, even though it remains higher than that observed in the other European
      countries participating in this study. This high use can be explained in part by
      the observation that, in around half the cases, it corresponds to occasional use.
      In contrast, the use of antidepressants has increased. In subjects with recent
      mood disorders or anxiety disorders, the use of AX-HY remains higher than that of
      antidepressants. Finally among users of AX-HY, only half of them had presented a
      mood disorder, anxiety disorder or alcohol use disorder during their lifetime,
      whereas this proportion rose to 80% for users of antidepressants.

PMID- 15959447
TI  - [On the interest of analyzing temperament in bipolar subjects].
AB  - Temperaments in bipolar subjects, as observed by Kraepelin and later re-dynamized
      and operationalized by Akiskal, have given rise to various studies, which results
      are hereby synthesized. In the light of these studies, the evaluation of
      temperaments allows to define subgroups of bipolar subjects, in order to sharpen
      diagnosis and therefore be able to propose more accurate treatment. A depressive
      temperament is linked to more frequent thymic relapses, on a depressive slope and
      it is associated with more frequent comorbid anxiety disorder and with an
      increased suicidal risk. A hyperthymic temperament is linked to manic relapses
      and is more likely to switch mood when patients were treated with
      antidepressants. A thymic episode that appears in a temperament of the opposite
      polarity will result in a mixed episode. Temperament evaluation is also helpful
      in choosing drug treatments. Practical clinical benefits can be gained from the
      study and analysis of those temperaments. As a further development, it could be
      useful to characterize euthymic period by a dimensional approach.

PMID- 15959448
TI  - [From the biology of trauma to secondary preventive pharmalogical measures for
      post-traumatic stress disorders].
AB  - Of all the psychological complications that an individual is likely to present
      with when confronted with an exceptional event, the Post-Traumatic Stress
      Disorder is characterized by being progressive, frequent, invalidating, strongly
      associated with comorbidity, and having the tendency to become chronic if it is
      not detected clinically. By definition, it is threatening and produces an intense
      fear reaction. The traumatic event is a situation of extreme stress, not only
      capable of altering the physical and psychological homeostasis of the individual,
      but is also recognized as determinant in the aetiopathology of complications. The
      intensity of this distress can be identified clinically and physiologically, and
      is currently considered as an important risk factor for the development of PTSD
      later on, together with other pre-, peri- and post-traumatic factors. In fact,
      the most studied field is the therapeutic approach, in particular drug treatment,
      of the fully-constituted disorder, although this actually represents tertiary
      prevention. Even though primary prevention seems to concern Medicine very little,
      any prospect of performing secondary prevention should begin by rapid
      identification of the risk or vulnerability factors and should allow a population
      at risk from developing complications to be defined. Its potential therapeutic
      impact brings together psychotherapeutic and drug treatment, since it is only
      this combination that seems able to allow the most favourable clinical outcome to
      be achieved for an individual, who is confronted by an out-of-the-ordinary event.
      The aims of secondary prevention strategies are, for example, to reduce the
      incidence of acute PTSD in patients seen following the event. The benefits for
      the individual and for the society can easily be measured in terms of the
      consequences on his/her social, professional and family life, or in terms of
      cost. The usefulness of this prevention can also be measured by the possible ways
      that other conditions, comorbid to PTSD, are controlled, such as anxiety
      disorders, depression and substance abuse, for example. Secondary prevention
      strategies may also be aimed at determining the therapeutic impact, by preventing
      or moderating the appearance of an acute stress, or even by contributing in
      avoiding the onset of chronic PTSD. Psychopharmacology of the immediate and post
      immediate disorders, however, remains a field which has been studied very little.
      Reduction or control of the high, prolonged level of hyperarousal phenomena or
      hypersensitization of the hypothalamo-pituitary axis, would contribute to the
      comfort of the individual, and would participate in the prevention of PTSD. Based
      on current knowledge of the neurobiology of trauma, we look into the existing and
      potential pharmacological possibilities. Even though benzodiazepines tend to have
      an important role, knowledge of other drugs and therapeutic groups is rapidly
      increasing. In this review, we will see that the efficacy of anti-adrenergic
      drugs and certain other anxiolytics is now well-documented, this opening the door
      to their use in the future. Other drug groups offer interesting, well-proven
      approaches, such as serotoninergic drugs, CRF or NPY antagonists, NMDA
      antagonists, anticonvulsants or other GABAergic agents. In view of this disorder,
      which represents a true public health problem, we consider that it is now
      possible to widen the horizons of our drug therapy, in combination with any
      necessary psychotherapeutic treatment, to reach the heart of the traumatic event,
      that often upsets the victims, both by the psychological suffering it induces,
      and the loss of his/her social, family and professional references and support
      structures.

PMID- 15959449
TI  - [The information of the schizophrenic patient: actuality].
AB  - Social isolation has got to be one of the greatest losses in schizophrenia. For
      many authors, people with schizophrenia can have no friends, no spouse, and
      sometimes no family. Two thirds of patients with schizophrenia return to their
      parents' house after discharge from a hospital for the first psychosi episode.
      Family members generally receive very little education as to what they can
      expect. They may not know the importance of medication compliance. Family members
      are the primary victims of violence from psychotic individuals, usually their own
      son or daughter, and most families cannot believe their own son or daughter would
      be capable of such a thing. Although families are usually the main care givers at
      the beginning of schizophrenia they often find their experience very frustrating
      for a number of reasons, and relationships suffer. Family education and support
      have been shown to improve outcomes considerably and family education is the
      second strongest factor in relapse prevention. Without education and good relapse
      prevention families often burst out. Most of the homeless mentally ill in
      downtown city cores have lost their family relationships. It is not a reflection
      on their families so much as the lack of adequate treatment and support. The
      families tried and tried and lost their ill relative. A patient writes: "My
      father lives just outside of Monaco. My mother developed Alzheimer's a couple of
      years ago or so and with a series of mild strokes died recently. I haven't seen
      either of them very much in the last fifteen years. I have a sister, Nicole, who
      also lives in Paris. I lost those relationships to some degree over the years. I
      am rebuilding them now. Enter the professional friend, the case manager, usually
      in cases where the individual is quite disabled by schizophrenia and/or at
      considerable risk of relapse, and usually when the individual has lost their
      family relationships to some degree. I had a case manager for several years and
      always looked forward to her visits. Case managers help negotiate compliance to
      medication, housing, meaningful activity, substance abuse, poverty, isolation,
      and everything else living in the community can throw at you. Without a spouse
      you tend to spend a lot of time alone. One of the main reasons Marie-Claude and I
      moved in with each other was that neither of us was enjoying living alone. It was
      very romantic at first but now we are just friends who see less and less of each
      other. I suspect schizophrenia interferes with the quality and depth of
      relationships you have with other people. Amongst the people I know,
      schizophrenia has meant a pretty solitary life of poverty. I have a lot of
      acquaintances, and colleagues, but few close friends when not at work. Over the
      last ten years of living with schizophrenia on medication it is celibacy that has
      hurt the most. It saps the life out of you, your self confidence, your self
      esteem. In some Scandinavian countries and Holland disabled people are allowed
      monthly visits by state approved sex workers. To me that is only common sense. To
      live without sex is unnatural and can only cause emotional suffering. We don't
      recognize the importance of quality sexual experience in keeping people healthy
      and happy in France. That doesn't mean it isn't I have a pretty high profile in
      my community through the meaningful activity I do. From having a half dozen names
      and faces to remember, I now have what seems like hundreds. I have a lot of
      trouble remembering people's names and faces. I am still meeting new people but
      I'm rarely invited to socialize with any after work. They have families, full
      time jobs, kids, cars, cottages, etc. My life at home is pretty solitary. It's a
      nuisance to travel across the city to visit people. There are few people that I
      share a similar background with. Since people with schizophrenia tend to have
      trouble learning new things, and change very little as a result, we tend to have
      trouble making new friends. People with schizophrenia can come alive talking
      about things in the past before they became ill. It's as if their life grinded to
      halt when they became sick. I'm stuck in the mid seventies, and that's the music
      I like. Everybody I know with schizophrenia is quite isolated socially and I
      don't really know why. That is especially true for the older people in my age
      group. Younger people seem to be doing much better. Many still live with their
      parents. Most older people live alone. There is also the odd person who recovers
      well, returns to a career, and marries someone without schizophrenia. In cases
      where marriage predates the onset of schizophrenia, the outcome is often divorce
      although women are more likely to stick with their husbands with schizophrenia
      than vice versa, especially if there are already children. I hope the next
      generation who appears to be less disabled survives better than people of my age
      with schizophrenia. The goal of community integration is one that requires: more
      effective treatments and/or more financial support and/or a compassionate non
      discriminating community. The combination of early diagnosis and atypical
      medications will change the face of schizophrenia. I'm not expecting more
      financial support from the government, but many more people with schizophrenia
      will start working again instead. Their social networks will develop but social
      networks are probably the hardest hit in schizophrenia. It's better that you
      never lose your friends in the first place". This testimony shows how the
      information of the schizophrenic patient is necessary, and underlines the
      importance of the relationships between the patient and his family. Our article
      insists on this theme, rarely developed in the literature.

PMID- 15959450
TI  - [Cost-effectiveness analysis of schizophrenic patient care settings: impact of an
      atypical antipsychotic under long-acting injection formulation].
AB  - Schizophrenia is a disease affecting the young adults and amounts to
      approximately 300,000 people in France. The French public psychiatric sector
      takes care of approximately 150,000 adults schizophrenics: 50% benefit from
      ambulatory care, 50% are in partial or full-time hospitalization care.
      Schizophrenia represents the first diagnosis that psychiatric sectors take in
      charge. The costs associated with schizophrenia, mainly hospital costs, are
      important and were estimated at 2% of the total medical costs in France. In the
      French social welfare system, the social costs (pensions, allowances, managements
      of custody or guardianship by social workers) are also to be taken into account:
      it amounts to a third of the global direct cost. Schizophrenia also generates
      indirect costs (losses of productivity and premature deaths) which would be at
      least equal, or even more important, than direct medical costs. The non
      compliance to the antipsychotic treatment is a major problem with people
      suffering from schizophrenia. Indeed the lack of compliance to the treatment,
      estimated at 20 to 40%, is a major handicap for schizophrenic patient
      stabilization. The poor level of compliance is due to many various causes:
      adverse effects that are considered unbearable, medicine viewed as persecutory,
      negation of the disease, nostalgia for the productive phases of the disease, lack
      of social support, complexity of the prescription, relapse itself. Compliance is
      thus influenced by the patient's clinical features, local provision of health
      care and the specific nature of the drug (adverse effects, pharmaceutical
      formulation). The atypical antipsychotics present fewer extrapyramidal side
      effects and reduce the cognitive deficits associated with the disease, which
      results in improved compliance. Long-acting injectable antipsychotics allow a
      better therapeutic compliance and thus better efficacy of the treatment. Several
      studies have shown a significant improvement in compliance related to the
      pharmaceutical formulation of antipsychotics. Hospitalization and relapse risks
      are lower in compliant than in non-compliant patients. OBJECTIVES: The main
      objective of this pharmacoeconomic analysis is to evaluate the impact in terms of
      medical benefits and costs of the following strategies: 1. Risperidone long
      acting injection: first long-acting injectable atypical antipsychotic; 2.
      Haloperidol depot: long-acting injectable conventional neuroleptic; 3.
      Olanzapine: atypical antipsychotic available commercially in oral formulation.
      METHODS: The target population defined for the study are young schizophrenic
      patients treated for at least 1 year and whose disorder has not been diagnosed
      for longer than 5 years. The time horizon is 2 years. A cost-effectiveness
      analysis is performed. The perspective adopted is the French Health System. The
      main hypothesis of the model is that an increase in compliance linked to the use
      of long-acting injectable formulation could lead to an increased efficacy and a
      modification of the cost-effectiveness ratio. A decision tree was built. Six
      periods of follow-up are identified with a duration of 4-months per period. The
      tree contains 3 principal arms, each one corresponding to a specific treatment:
      risperidone LA injection, haloperidol decanoate and olanzapine. For each arm, at
      the chance node, two health states are identified: either the patient responds
      favourably to the treatment or does not respond favourably and requires a switch
      to another drug treatment. After a period of response, the patient can either
      remain in the same state or experiences a clinical deterioration. If the patient
      presents a clinical deterioration, he can either go back to a positive response
      state after a period of intensive follow-up or remain in an insufficient response
      state; in this case, a change of antipsychotic treatment is necessary. In the
      model, a patient should receive four different treatments before a long-term
      hospitalization takes put in place. According to the market authorization
      labelling, clozapine is proposed only as a 2nd or 3rd line therapeutic option, so
      when at least one or two successive neuroleptics have failed. The efficacy data
      used in the model are provided by clinical research recently published. These
      studies estimate the efficacy of oral risperidone, LA risperidone, olanzapine,
      and treatment by haloperidol. When available data in the literature were
      insufficient, the opinion of experts was sought. The effectiveness criteria is
      the rate of patients treated successfully: patients responding to the initial
      treatment with the possibility of experiencing one or two episodes of clinical
      deterioration but without requiring a switch to another drug during 2 years of
      follow-up. The base case is as follows: efficacy for oral risperidone is used for
      the LA risperidone strategy, increased by 10% within the first 4 months of follow
      up; efficacy for oral haloperidol is used for haloperidol depot, increased by 5%
      within the first 4 months of follow-up; for olanzapine, observed data in clinical
      trials were applied. The hypotheses for long acting forms are rather conservative
      because the increase of efficacy which can be expected for the long-acting
      injectable formulations varies between 5% to more than 30% according to the
      literature data. The analysis of sensibility includes three scenarios: scenario
      1: for LA risperidone, 5% of patients treated successfully improvement in regard
      to oral risperidone instead of 10% in the base case; scenario 2: for haloperidol
      depot, 10% of patients treated successfully improvement in regard of oral
      haloperidol instead of 5% in the base case; scenario 3: the results of an open
      trial conducted within the framework of the LA risperidone license are used,
      leading to an increase of up to 13,3% of the rate of successfully treated
      patients, compared to oral risperidone literature data. As for the side effects,
      only extrapyramidal symptoms were considered. Other side effects are described in
      the literature such as the obesity or the occurrence of a diabetes; these effects
      were not taken into account in the model, their impact on the cove-rage of
      schizophrenic patients and on resources utilisation being poorly known. Only
      direct medical costs were considered in the pharmaco-economic analysis. Two types
      of costs were identified: hospital costs and community care costs. The stays in
      overnight hospitalisation and day hospitalisation were derived from the Disease
      Related Groups (DRG) and valued from the data of the National Cost Study (Etude
      Nationale de Couts; 1999). The DRGs corresponding to the diagnosis of
      schizophrenia are the DRG 627 (complete hospitalization) and DRG 819 (day
      hospitalisation). Ambulatory care: procedures and visits, were valued in euros in
      reference with the tariffs for reimbursement issued in the Naming General of the
      Professional Acts (NGAP) and published by the French National Health Insurance
      (Year 2001). Medication consumption was quantified by using the daily dosage
      specified in the the MAA and the French prescription database IMS-Dorema. The
      cost of medicines was valued from tariffs 2001 (SEMPEX). LA risperidone price
      being not fixed to date, the reserved hypothesis is a 141,62 Euro retail price.
      As schizophrenia is listed among the diseases reimbursed at a 100% rate by the
      Health insurance, out of pocket expenses by patient are not considered in the
      analysis. The cost for the extrapyramidal effects was attributed to all the
      strategies. This cost was calculated according to the rates of extrapyramidal
      effects occurrence collected in the literature. Globally, in the published
      studies, the incidence of the side effects for the patients treated by olanzapine
      or risperidone is similar. It was thus decided by the experts to use the same
      rate of occurrence for extrapyramidal effects for olanzapine and risperidone
      (20%). This rate is 40% for haloperidol decanoate, 10% for oral clozapine. For
      the cost estimation, the expenses for treating a schizophrenic patient for two
      years were taken into account. RESULTS: The results show that in two years, LA
      risperidone is more effective than the two other antipsychotics. After 2 years,
      the rate of patients treated successfully is 82,7% for LA risperidone, 74,8% for
      olanzapine and 57,3% for haloperidol depot. The 2 year-cost per patient treated
      by LA risperidone is 14,055 Euro. This cost is 14,351 Euro and 17,203 Euro
      respectively for the strategies olanzapine and haloperidol depot. The cost
      efficacy ratios per patient successfully treated are 16,995 Euro for the strategy
      LA risperidone, 19,186 Euro for olanzapine and 30,023 Euro for haloperidol depot.
      LA risperidone is a dominant strategy compared with both olanzapine and
      haloperidol depot. Scenario 1 shows that LA risperidone strategy remains the most
      effective. Indeed, this strategy allows a response increase of 3,5% regarding
      olanzapine strategy and of 21% regarding haloperidol depot strategy. Under the
      hypothesis tested in scenario 1, LA risperidone is a partial dominant strategy
      against olanzapine and a total dominant strategy against haloperidol depot. In
      scenario 2, as efficacy is improved for haloperidol decanoate (61,10%), a
      decrease of 1,763 Euro in the cost per patient treated is observed for this
      strategy. Cost per patient treated successfully and efficacy for LA risperidone
      and olanzapine are the same than in the base case. LA risperidone is a total
      dominant strategy against olanzapine and haloperidol decanoate. In scenario 3,
      the rate of patients treated successfully at 2 years is 88,6% for LA risperidone
      with a cost per patient of 12,347 Euro. LA risperidone is dominant against
      olanzapine and haloperidol depot. DISCUSSION AND CONCLUSION: The schizophrenia is
      a relatively frequent disease. (ABSTRACT TRUNCATED)

PMID- 15959451
TI  - [Schizophrenia and amphetamine dependence. A case report].
AB  - Whereas observations of psychotic disorders induced by amphetamines are common,
      few observations described the impact of chronic amphetamine abuse on
      schizophrenic patients. We report the case of a schizophrenic patient who
      presented with amphetamine dependence for several years, without other
      accompanying addiction. CASE REPORT: During his adolescence, Mr. X. gradually
      developed delusional beliefs of persecution and telepathy. He believed that the
      other pupils and teachers spoke about him in malicious terms. At the age of 23,
      Mr. X began to consume 60-100 mg/week of amphetamines orally. He consumed
      amphetamines during 7 years. The delusions, in particular the auditory
      hallucinations worsened after the use of amphetamines. Subsequently, he married
      and was declared unfit for national service due to the psychotic disorders. Mr. X
      received neuroleptic treatment with moderate effects on the psychotic symptoms.
      Between the age of 24 and 30, the patient presented persecutory, megalomanic and
      physical transformation beliefs, delusions of being controlled as well as
      auditory, somatic-tactile and visual hallucinations. At the age of 30, while he
      had stopped his consumption of amphetamines for 9 months, the patient,
      overwhelmed with the delusions, murdered his wife. He was sent in jail for 13
      months, and subsequently hospitalized for one year in a high security psychiatric
      department and 7 years in our psychiatric department. The neuroleptic treatment
      was effective, particularly against the hallucinations. Following stabilisation,
      the symptomatology of the patient was marked by a disorganization syndrome,
      including prominent thought disorder, disorganized speech, associative loosening,
      frequent derailments and negative signs of schizophrenia, in particular affective
      flattening and blunting of emotional expression. When the patient was 43, a trial
      discharge was authorized owing to improvement of his condition. The neuroleptic
      treatment was switched with single-drug olanzapine therapy, 10 mg/day which
      improved the negative symptoms. Mr. X. resumed part-time professional activities
      and remarried. DISCUSSION: The patient fulfilled the DSM IV criteria for
      schizophrenia and for amphetamine dependence assessed using the Composite
      International Diagnostic Interview (CIDI). He presented, in particular,
      withdrawal syndrome when amphetamines were discontinued. The amphetamine
      consumption was followed by a marked deterioration in the delusions, particularly
      the hallucinations. Worsening of the positive symptoms in schizophrenic patients
      by amphetamines has been established in single dose studies, in particular
      characterized by persecutory delusions and hallucinations. On the other hand,
      amphetamines tend to transiently and moderately reduce the negative symptoms.
      Some stu-dies have shown that amphetamine consumption promoted violent acting out
      in non-schizophrenic subjects. In our observation, the acting out may be not
      related to the acute effects of these substances, since it occurred 9 months
      after stated discontinuation of amphetamine consumption. However, the cerebral
      toxicity and psycho-behavioural disturbances related to amphetamines might be
      prolonged after withdrawal. In non-schizophrenic patients, the existence of
      prolonged neurotoxicity of amphetamines and related psycho-behavioral
      disturbances has been suggested. The prolonged administration of amphetamines to
      animals produces neuro-axonal degeneration in the striatum, the frontal cortex,
      the nucleus accumbens and the amygdala. In human, there are some evidence of
      persistant deteriorations of the serotoninergic and dopaminergic systems in the
      caudate nucleus, the putamen and the nucleus accumbens following amphetamine
      consumption. CONCLUSION: The neurobiological and psycho-behavioural effects of
      amphetamines may be prolonged following withdrawal in both schizophrenic and non
      schizophrenic patients.

PMID- 15959452
TI  - Lead exposure from indoor firing ranges among students on shooting teams--Alaska,
      2002-2004.
AB  - CDC recognizes blood lead levels (BLLs) of >/=25 microg/dL in adults and >/=10
      microg/dL in children aged </=6 years as levels of concern; no similar level has
      been set for older children and adolescents. During 2002-2004, the Alaska
      Environmental Public Health Program (EPHP) conducted lead-exposure assessments of
      school-based indoor shooting teams in the state, after a BLL of 44 microg/dL was
      reported in a man aged 62 years who coached a high school shooting team in
      central Alaska. This report summarizes the results of the EPHP investigation of
      potential lead exposure in 66 members of shooting teams, aged 7-19 years, who
      used five indoor firing ranges. The findings suggest that improper design,
      operation, and maintenance of ranges were the likely cause of elevated BLLs among
      team members at four of the five firing ranges. Public health officials should
      identify indoor firing ranges that have not implemented lead-safety measures and
      offer consultation to reduce the risk for lead exposure among shooters, coaches,
      and employees.

PMID- 15959453
TI  - Seroprevalence of poliovirus antibodies among children in a Dominican community-
      Puerto Rico, 2002.
AB  - Although the Region of the Americas was certified as polio-free in 1994, an
      outbreak of paralytic poliomyelitis associated with circulating vaccine-derived
      poliovirus (cVDPV) occurred during July 2000-July 2001 on the Caribbean island of
      Hispaniola. A total of 21 cases of paralytic polio associated with type 1 oral
      poliovirus vaccine (OPV) strain were reported in Haiti and the Dominican Republic
      (DR). Outbreaks from cVDPV occur among children in communities with low immunity
      levels to polioviruses and the absence of circulation of wild poliovirus (WPV).
      The U.S. territory of Puerto Rico (PR), located approximately 72 miles east of
      DR, has not had a case of paralytic polio since 1974. However, because of its
      proximity to DR and concerns that visitors and immigrants from DR (who tend to
      live in a separate community in PR) might not be fully vaccinated against
      polioviruses, the PR Department of Health (PRDH) and CDC assessed the
      seroprevalence of poliovirus antibodies among children aged 7-60 months in a
      predominantly DR community of PR. This report describes the results of that
      assessment, which indicated high levels of seropositivity for all three
      poliovirus serotypes. If vaccination rates remain high, the risk for a polio
      outbreak in this community is low. However, until all threats of poliovirus are
      eliminated globally, high rates of vaccination among preschool children must be
      ensured to prevent outbreaks of paralytic polio from any source (e.g., imported
      WPV, laboratory strains, or cVDPV) in the United States and its territories.

PMID- 15959454
TI  - Progress in measles control--Zambia, 1999-2004.
AB  - Zambia, a southern African country with estimated population of 11.6 million in
      2005, reported 1,698-23,518 measles cases annually during 1991-1999. During that
      period, measles was considered one of the five major causes of morbidity and
      mortality among children aged <5 years. During 1999-2004, the challenge of
      controlling measles led Zambia to try several strategies in succession. In
      addition to a single dose of measles vaccine offered at age 9 months through
      routine services, in 1999, measles supplemental immunization activities (SIAs)
      targeting children aged 9 months-4 years were held in four urban centers. Those
      activities were followed in 2000 by a subnational measles SIA targeting children
      aged 9 months-4 years in approximately half of the country's 72 districts. In
      2003, Zambia adopted a strategy of accelerated measles control that included
      strengthening routine vaccination, providing a second opportunity for measles
      immunization for all children, and conducting case-based surveillance. As part of
      this strategy, a nationwide measles SIA targeting all children aged 6 months-14
      years was conducted in 2003. This report summarizes progress in measles control
      in Zambia during 1999--2004, as measured through surveillance data, which
      demonstrates a marked reduction in measles transmission after the 2003 SIA.

PMID- 15959455
TI  - Differential effect of PARP-2 deletion on brain injury after focal and global
      cerebral ischemia.
AB  - Poly(ADP-ribose) polymerase-2 (PARP-2) is a member of the PARP enzyme family,
      and, similarly to PARP-1, catalyzes the formation of ADP-ribose polymers in
      response to DNA damage. While PARP-1 overactivation contributes to ischemic cell
      death, no information is available regarding the role of PARP-2. In this study,
      we evaluated the impact of PARP-2 deletion on histopathological outcome from two
      different experimental models of cerebral ischemia. Male PARP-2-/- mice and wild
      type (WT) littermates were subjected to either 2 h of middle cerebral artery
      occlusion (MCAO) followed by 22 h reperfusion, or underwent 10 mins of KCl
      induced cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) and 3
      day survival. After MCAO, infarct volume was reduced in PARP-2-/- mice (38%+/-12%
      of contralateral hemisphere) compared with WT (64%+/-16%). After CA/CPR, PARP-2
      deletion significantly increased neuronal cell loss in the hippocampal CA1 field
      (65%+/-36% ischemic neurons) when compared with WT mice (31%+/-33%), with no
      effect in either striatum or cortex. We conclude that PARP-2 is a novel
      executioner of cell death pathways in focal cerebral ischemia, but might be a
      necessary survival factor after global ischemia to mitigate hippocampal delayed
      cell death.

PMID- 15959456
TI  - Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after
      focal cerebral ischemia.
AB  - In the adult rodent, stroke induces an increase in endogenous neural progenitor
      cell (NPC) proliferation in the subventricular zone (SVZ) and neuroblasts migrate
      towards the ischemic boundary. We investigated the role of stromal cell-derived
      factor 1alpha (SDF-1alpha) in mediating NPC migration after stroke. We found that
      cultured NPCs harvested from the normal adult SVZ, when they were overlaid onto
      stroke brain slices, exhibited significantly (P<0.01) increased migration (67.2+/
      25.2 microm) compared with the migration on normal brain slices (29.5+/-29.5
      microm). Immunohistochemistry showed that CXCR 4, a receptor of SDF-1alpha, is
      expressed in the NPCs and migrating neuroblasts in stroke brain. Blocking SDF
      1alpha by a neutralizing antibody against CXCR 4 significantly attenuated stroke
      enhanced NPC migration. ELISA analysis revealed that SDF-1alpha levels
      significantly increased (P<0.01) in the stroke hemisphere (43.6+/-6.5 pg/mg) when
      compared with the normal brain (25.2+/-1.9 pg/mg). Blind-well chamber assays
      showed that SDF-1alpha enhanced NPC migration in a dose-dependent manner with
      maximum migration at a dose of 500 ng/mL. In addition, SDF-1alpha induced
      directionally selective migration. These findings show that SDF-1alpha generated
      in the stroke hemisphere may guide NPC migration towards the ischemic boundary
      via binding to its receptor CXCR 4 in the NPC. Thus, our data indicate that SDF
      1alpha/CXCR 4 is important for mediating specific migration of NPCs to the site
      of ischemic damaged neurons.

PMID- 15959457
TI  - Depressed responses to applied and synaptically-released GABA in CA1 pyramidal
      cells, but not in CA1 interneurons, after transient forebrain ischemia.
AB  - Transient cerebral ischemia kills CA1 pyramidal cells of the hippocampus, whereas
      most CA1 interneurons survive. It has been proposed that calcium-binding
      proteins, neurotrophins, and/or inhibitory neuropeptides protect interneurons
      from ischemia. However, different synaptic responses early after reperfusion
      could also underlie the relative vulnerabilities to ischemia of pyramidal cells
      and interneurons. In this study, we used gramicidin perforated patch recording in
      ex vivo slices to investigate gamma-aminobutyric acid (GABA) synaptic function in
      CA1 pyramidal cells and interneurons 4 h after a bilateral carotid occlusion
      accompanied by hypovolemic hypotension. At this survival time, the amplitudes of
      both miniature inhibitory postsynaptic currents (mIPSCs) and GABA-evoked currents
      were reduced in CA1 pyramidal cells, but not in CA1 interneurons. In addition,
      the mean rise time of mIPSCs was reduced in pyramidal cells. The reversal
      potential for the GABA current (E(GABA)) did not shift toward depolarizing values
      in either cell type, indicating that the driving force for chloride was unchanged
      at this survival time. We conclude that early during reperfusion GABAergic
      neurotransmission is attenuated exclusively in pyramidal neurons. This is likely
      explained by reduced GABAA receptor sensitivity or clustering and possibly also
      reduced GABA release, rather than by an elevation of intracellular chloride.
      Impaired GABA function may contribute to ischemic neuronal death by enhancing the
      excitability of CA1 pyramidal cells and facilitating N-methyl-D-aspartic acid
      channel opening. Therefore, normalizing GABAergic function might be a useful
      pharmacological approach to counter excessive, and potentially excitotoxic,
      glutamatergic activity during the postischemic period.

PMID- 15959458
TI  - Adult neurogenesis and the ischemic forebrain.
AB  - The recent identification of endogenous neural stem cells and persistent neuronal
      production in the adult brain suggests a previously unrecognized capacity for
      self-repair after brain injury. Neurogenesis not only continues in discrete
      regions of the adult mammalian brain, but new evidence also suggests that neural
      progenitors form new neurons that integrate into existing circuitry after certain
      forms of brain injury in the adult. Experimental stroke in adult rodents and
      primates increases neurogenesis in the persistent forebrain subventricular and
      hippocampal dentate gyrus germinative zones. Of greater relevance for
      regenerative potential, ischemic insults stimulate endogenous neural progenitors
      to migrate to areas of damage and form neurons in otherwise dormant forebrain
      regions, such as the neostriatum and hippocampal pyramidal cell layer, of the
      mature brain. This review summarizes the current understanding of adult
      neurogenesis and its regulation in vivo, and describes evidence for stroke
      induced neurogenesis and neuronal replacement in the adult. Current strategies
      used to modify endogenous neurogenesis after ischemic brain injury also will be
      discussed, as well as future research directions with potential for achieving
      regeneration after stroke and other brain insults.

PMID- 15959459
TI  - Free radical-mediated damage to barrier function is not associated with altered
      brain morphology in high-altitude headache.
AB  - The present study combined molecular and neuroimaging techniques to examine if
      free radical-mediated damage to barrier function in hypoxia would result in
      extracellular edema, raise intracranial pressure (ICP) and account for the
      neurological symptoms typical of high-altitude headache (HAH) also known as acute
      mountain sickness (AMS). Twenty-two subjects were randomly exposed for 18 h to
      12% (hypoxia) and 21% oxygen (O2 (normoxia)) for collection of venous blood (0 h,
      8 h, 15 h, 18 h) and CSF (18 h) after lumbar puncture (LP). Electron paramagnetic
      resonance (EPR) spectroscopy identified a clear increase in the blood and CSF
      concentration of O2 and carbon-centered free radicals (P<0.05 versus normoxia)
      subsequently identified as lipid-derived alkoxyl (LO*) and alkyl (LC*) species.
      Magnetic resonance imaging (MRI) demonstrated a mild increase in brain volume
      (7.0+/-4.8 mL or 0.6%+/-0.4%, P<0.05 versus normoxia) that resolved within 6 h of
      normoxic recovery. However, there was no detectable evidence for gross barrier
      dysfunction, elevated lumbar pressures, T2 prolongation or associated neuronal
      and astroglial damage. Clinical AMS was diagnosed in 50% of subjects during the
      hypoxic trial and corresponding headache scores were markedly elevated (P<0.05
      versus non-AMS). A greater increase in brain volume was observed, though this was
      slight, independent of oxidative stress, barrier dysfunction, raised lumbar
      pressure, vascular damage and measurable evidence of cerebral edema and only
      apparent in the most severe of cases. These findings suggest that free-radical
      mediated vasogenic edema is not an important pathophysiological event that
      contributes to the mild brain swelling observed in HAH.

PMID- 15959460
TI  - Persistent arterial hyperammonemia increases the concentration of glutamine and
      alanine in the brain and correlates with intracranial pressure in patients with
      fulminant hepatic failure.
AB  - In this prospective study of patients with fulminant hepatic failure (FHF), we
      tested the hypothesis that arterial hyperammonemia results in cerebral
      accumulation of the osmotic active amino acids glutamine and alanine, processes
      that were expected to correlate with intracranial pressure (ICP). By using in
      vivo brain microdialysis technique together with ICP monitoring in 17 FHF
      patients (10 females/7 males; median age 49 (range 18 to 66) years), we found
      that arterial ammonia concentration correlated to brain content of glutamine
      (r=0.47; P<0.05) but not to alanine. A persisting high arterial ammonia
      concentration (above 200 micromol/L) characterized patients who developed high
      ICP (n=8) while patients who did not experience surges of increased ICP (n=9) had
      a decline in the ammonia level (P<0.05). Moreover, brain glutamine and alanine
      concentrations were higher at baseline and increased further in patients who
      developed intracranial hypertension compared with patients who experienced no
      surges of high ICP. Brain glutamine concentration increased 32% from baseline to
      6536 (697 to 9712) micromol/L (P<0.05), and alanine 44% from baseline to 104 (81
      to 381) micromol/L (P<0.05). Brain concentration of glutamine (r=0.59, P<0.05),
      but not alanine, correlated to ICP. Also arterial ammonia concentration
      correlated to ICP (r=0.73, P<0.01). To conclude, this study shows that
      persistence of arterial hyperammonemia is associated with profound changes in the
      cerebral concentration of glutamine and alanine. The elevation of brain glutamine
      concentration correlated to ICP in patients with FHF.

PMID- 15959461
TI  - Regional temperature changes in the brain during somatosensory stimulation.
AB  - Time-dependent variations in the brain temperature (Tt) are likely to be caused
      by fluctuations of cerebral blood flow (CBF) and cerebral metabolic rate of
      oxidative consumption (CMRO2) both of which are seemingly coupled to alterations
      in neuronal activity. We combined magnetic resonance, optical imaging,
      temperature sensing, and electrophysiologic methods in alpha-chloralose
      anesthetized rats to obtain multimodal measurements during forepaw stimulation.
      Localized changes in neuronal activity were colocalized with regional increases
      in Tt (by approximately 0.2%), CBF (by approximately 95%), and CMRO2 (by
      approximately 73%). The time-to-peak for Tt (42+/-11 secs) was significantly
      longer than those for CBF and CMRO2 (5+/-2 and 18+/-4 secs, respectively) with a
      2-min stimulation. Net heat in the region of interest (ROI) was modeled as being
      dependent on the sum of heats attributed to changes in CMRO2 (Qm) and CBF (Qf) as
      well as conductive heat loss from the ROI to neighboring regions (Qc) and to the
      environment (Qe). Although tissue cooling because of Qf and Qc can occur and are
      enhanced during activation, the net increase in Tt corresponded to a large rise
      in Qm, whereas effects of Qe can be ignored. The results show that Tt increases
      slowly (by approximately 0.1 degrees C) during physiologic stimulation in alpha
      chloralose anesthetized rats. Because the potential cooling effect of CBF depends
      on the temperature of blood entering the brain, Tt is mainly affected by CMRO2
      during functional challenges. Implications of these findings for functional
      studies in awake humans and temperature regulation are discussed.

PMID- 15959462
TI  - Location and function of VPAC1, VPAC2 and NPR-C receptors in VIP-induced
      vasodilation of porcine basilar arteries.
AB  - Vasoactive intestinal peptide (VIP) is a vasodilator peptide present in
      cerebrovascular nerves. Vasoactive intestinal peptide can activate VPAC1, VPAC2
      and the NPR-C receptor. This study sought to determine the receptors involved in
      VIP-induced vasodilation of porcine basilar arteries. Porcine basilar arteries
      contained the messenger ribonucleic acid of all three receptors.
      Immunocytochemical analysis of porcine basilar arteries revealed that the VPAC1
      receptor is expressed on the endothelium, VPAC2 on the outer layers of the media
      and the NPR-C receptor throughout the artery, including nerves. Vasodilator
      responses to all receptor agonists showed that the receptors are functional. The
      vasodilator response to the VPAC1 receptor agonist was inhibited by L-NAME and
      abolished by endothelial denudation. Vasodilation induced by Ro-25-1553, the
      VPAC2 agonist, was unaffected by NOS inhibition or removal of the endothelium.
      Activation of the NPR-C receptor produced a vasodilation, which was susceptible
      to NOS inhibition and independent of endothelium. The vasodilator response to
      electrical stimulation at 20 Hz was attenuated by PG-99-465, the VPAC2
      antagonist. This study shows that all known VIP receptors are involved in VIP
      mediated vasodilation of porcine basilar arteries. The VPAC1 receptor is located
      on the endothelium and elicits vasodilation by generating nitric oxide (NO). The
      VPAC2 receptor is mainly expressed in the outer layers of the smooth muscle and
      induces vasodilation independently of NO in response to VIP released from
      intramural nerves. The NPR-C receptor produces NO-dependent vasodilation
      independently of the endothelium by stimulation of nNOS in intramural nerves.

PMID- 15959463
TI  - Nestin-expressing cells divide and adopt a complex electrophysiologic phenotype
      after transient brain ischemia.
AB  - The intermediate filament nestin is upregulated in response to cerebral ischemia;
      the significance of this, however, is incompletely understood. Here, we used
      transgenic mice that express green fluorescent protein (GFP) under control of the
      nestin promotor to characterize the fate of nestin-expressing cells up to 8 weeks
      after 30 mins occlusion of the middle cerebral artery (MCAo) and reperfusion. The
      population of nestin-GFP+ cells increased in the ischemic lesion rim and core
      within 4 days, did not become TUNEL-positive, and was detectable up to 8 weeks in
      the lesion scar. Nestin-GFP+ cells proliferated in situ and underwent
      approximately one round of cell division. They were not recruited in large
      numbers from the subventricular zone (SVZ) as indicated by absence of colabeling
      with intracerebroventricularly injected dye DiI in the majority of nestin-GFP+
      cells. Nestin-GFP+ cells expressed the chondroitin sulfate proteoglycan NG2 and
      nestin protein, but typically lacked mature astrocytic markers, that is, glial
      fibrillary acid protein (GFAP) or S100beta. Vice versa, the majority of GFAP+
      cells lacked nestin-expression and surrounded the ischemic lesion by 4 days.
      Whole-cell patch-clamp recordings in acute brain slices from controls showed that
      only about half of nestin-GFP+ cells displayed complex membrane properties. In
      contrast, 4 days after the insult all nestin-GFP+ cells expressed these
      properties. We hypothesize that the change in physiologic properties induced by
      the ischemic insult is directed toward a specific function of nestin-expressing
      cells.

PMID- 15959464
TI  - Influence of therapeutic hypothermia on matrix metalloproteinase activity after
      traumatic brain injury in rats.
AB  - Recent evidence suggests that matrix metalloproteinases (MMPs) contribute to
      acute edema and lesion formation following ischemic and traumatic brain injuries
      (TBI). Experimental and clinical studies have also reported the beneficial
      effects of posttraumatic hypothermia on histopathological and behavioral outcome.
      The purpose of this study was to determine whether therapeutic hypothermia would
      affect the activity of MMPs after TBI. Male Sprague-Dawley rats were traumatized
      by moderate parasagittal fluid-percussion (F-P) brain injury. Seven groups
      (n=5/group) of animals were investigated: sham-operated, TBI with normothermia
      (37 degrees C), and TBI with hypothermia (33 degrees C). Normothermia animals
      were killed at 4, 24, 72 h and 5 days, and hypothermia animals at 24 or 72 h.
      Brain temperature was reduced to target temperature 30 mins after trauma and
      maintained for 4 h. Ipsilateral and contralateral cortical, hippocampal, and
      thalamic regions were analyzed by gelatin and in situ zymography. In traumatized
      normothermic animals, TBI significantly (P<0.005) increased MMP-9 levels in
      ipsilateral (right) cortical and hippocampal regions, compared with contralateral
      or sham animals, beginning at 4 h and persisting to 5 days. At 1, 3, and 5 days
      after TBI, significant increases in MMP-2 levels were observed. In contrast to
      these findings observed with normothermia, posttraumatic hypothermia
      significantly reduced MMP-9 levels. Hypothermic treatment, however, did not
      affect the delayed activation of MMP-2. Clarifying the mechanisms underlying the
      beneficial effects of posttraumatic hypothermia is an active area of research.
      Posttraumatic hypothermia may attenuate the deleterious consequences of brain
      trauma by reducing MMP activation acutely.

PMID- 15959465
TI  - Brain mechanisms linking language and action.
AB  - For a long time the cortical systems for language and actions were believed to be
      independent modules. However, as these systems are reciprocally connected with
      each other, information about language and actions might interact in distributed
      neuronal assemblies. A critical case is that of action words that are
      semantically related to different parts of the body (for example, 'lick', 'pick'
      and 'kick'): does the comprehension of these words specifically, rapidly and
      automatically activate the motor system in a somatotopic manner, and does their
      comprehension rely on activity in the action system?

PMID- 15959466
TI  - Neurosteroids: endogenous regulators of the GABA(A) receptor.
AB  - GABA(A) (gamma-aminobutyric acid type A) receptors mediate most of the 'fast'
      synaptic inhibition in the mammalian brain and are targeted by many clinically
      important drugs. Certain naturally occurring pregnane steroids can potently and
      specifically enhance GABA(A) receptor function in a nongenomic (direct) manner,
      and consequently have anxiolytic, analgesic, anticonvulsant, sedative, hypnotic
      and anaesthetic properties. These steroids not only act as remote endocrine
      messengers, but also can be synthesized in the brain, where they modify neuronal
      activity locally by modulating GABA(A) receptor function. Such 'neurosteroids'
      can influence mood and behaviour in various physiological and pathophysiological
      situations, and might contribute to the behavioural effects of psychoactive
      drugs.

PMID- 15959467
TI  - Compartments and their boundaries in vertebrate brain development.
AB  - Fifteen years ago, cell lineage restriction boundaries were discovered in the
      embryonic vertebrate hindbrain, subdividing it into a series of cell-tight
      compartments (known as rhombomeres). Compartition, together with segmentally
      reiterative neuronal architecture and the nested expression of Hox genes,
      indicates that the hindbrain has a truly metameric organization. This finding
      initiated a search for compartments in other regions of the developing brain. The
      results of recent studies have clarified where compartment boundaries exist, have
      shed light on molecular mechanisms that underlie their formation and have
      revealed an important function of these boundaries: the positioning and
      stabilization of local signalling centres.

PMID- 15959468
TI  - Male-specific fruitless specifies the neural substrates of Drosophila courtship
      behaviour.
AB  - Robust innate behaviours are attractive systems for genetically dissecting how
      environmental cues are perceived and integrated to generate complex behaviours.
      During courtship, Drosophila males engage in a series of innate, stereotyped
      behaviours that are coordinated by specific sensory cues. However, little is
      known about the specific neural substrates mediating this complex behavioural
      programme. Genetic, developmental and behavioural studies have shown that the
      fruitless (fru) gene encodes a set of male-specific transcription factors (FruM)
      that act to establish the potential for courtship in Drosophila. FruM proteins
      are expressed in approximately 2% of central nervous system neurons, at least one
      subset of which coordinates the component behaviours of courtship. Here we have
      inserted the yeast GAL4 gene into the fru locus by homologous recombination and
      show that (1) FruM is expressed in subsets of all peripheral sensory systems
      previously implicated in courtship, (2) inhibition of FruM function in olfactory
      system components reduces olfactory-dependent changes in courtship behaviour, (3)
      transient inactivation of all FruM-expressing neurons abolishes courtship
      behaviour, with no other gross changes in general behaviour, and (4)
      'masculinization' of FruM-expressing neurons in females is largely sufficient to
      confer male courtship behaviour. Together, these data demonstrate that FruM
      proteins specify the neural substrates of male courtship.

PMID- 15959469
TI  - Food-web topology: universal scaling in food-web structure?

PMID- 15959471
TI  - Save the people, too.

PMID- 15959472
TI  - Risks and benefits of dual-use research.

PMID- 15959473
TI  - Much whaling and gnashing of teeth.

PMID- 15959475
TI  - Biologists asked to breed a culture of responsibility in face of terrorism.

PMID- 15959476
TI  - Whaling divisions deepen as Japan pushes for credibility.

PMID- 15959477
TI  - US teams join hands to build dexterous robots.

PMID- 15959478
TI  - Gloomy outlook for Blair.

PMID- 15959479
TI  - Geologists call time on dating dispute.

PMID- 15959480
TI  - German tobacco papers reveal lump sums for health experts.

PMID- 15959482
TI  - Look out for rough drafts of mammal genomes.

PMID- 15959484
TI  - Conservation in Myanmar: under the gun.

PMID- 15959485
TI  - Science education: Hothouse High.

PMID- 15959487
TI  - No longer the upstart.

PMID- 15959486
TI  - Stem-cell therapies: the first wave.

PMID- 15959488
TI  - Images: keep a distinction between beauty and truth.

PMID- 15959489
TI  - Don't drop current vaccine until we have new ones.

PMID- 15959490
TI  - Coordinating vaccine use is best way to combat polio.

PMID- 15959496
TI  - Low-temperature physics: tunnelling into the chill.

PMID- 15959491
TI  - Japan's whaling plan under scrutiny.

PMID- 15959497
TI  - Genetics: LINEs in mind.

PMID- 15959499
TI  - Engineering: skimming the surface.

PMID- 15959498
TI  - Malaria: fungal allies enlisted.

PMID- 15959501
TI  - Cell biology: powerful curves.

PMID- 15959502
TI  - Nuclear physics: elusive magic numbers.

PMID- 15959503
TI  - Developmental biology: one source for muscle.

PMID- 15959504
TI  - Cell biology: new cog for a familiar machine.

PMID- 15959506
TI  - Genetics: relatedness among east African coelacanths.
AB  - Coelacanths were discovered in the Comoros archipelago to the northwest of
      Madagascar in 1952. Since then, these rare, ancient fish have been found to the
      south off Mozambique, Madagascar and South Africa, and to the north off Kenya and
      Tanzania -- but it was unclear whether these are separate populations or even
      subspecies. Here we show that the genetic variation between individuals from
      these different locations is unexpectedly low. Combined with earlier results from
      submersible and oceanographic observations, our findings indicate that a separate
      African metapopulation is unlikely to have existed and that locations distant
      from the Comoros were probably inhabited relatively recently by either dead-end
      drifters or founders that originated in the Comoros.

PMID- 15959507
TI  - Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition.
AB  - Revealing the mechanisms for neuronal somatic diversification remains a central
      challenge for understanding individual differences in brain organization and
      function. Here we show that an engineered human LINE-1 (for long interspersed
      nuclear element-1; also known as L1) element can retrotranspose in neuronal
      precursors derived from rat hippocampus neural stem cells. The resulting
      retrotransposition events can alter the expression of neuronal genes, which, in
      turn, can influence neuronal cell fate in vitro. We further show that
      retrotransposition of a human L1 in transgenic mice results in neuronal somatic
      mosaicism. The molecular mechanism of action is probably mediated through Sox2,
      because a decrease in Sox2 expression during the early stages of neuronal
      differentiation is correlated with increases in both L1 transcription and
      retrotransposition. Our data therefore indicate that neuronal genomes might not
      be static, but some might be mosaic because of de novo L1 retrotransposition
      events.

PMID- 15959509
TI  - Widespread magma oceans on asteroidal bodies in the early Solar System.
AB  - Immediately following the formation of the Solar System, small planetary bodies
      accreted, some of which melted to produce igneous rocks. Over a longer timescale
      (15-33 Myr), the inner planets grew by incorporation of these smaller objects
      through collisions. Processes operating on such asteroids strongly influenced the
      final composition of these planets, including Earth. Currently there is little
      agreement about the nature of asteroidal igneous activity: proposals range from
      small-scale melting, to near total fusion and the formation of deep magma oceans.
      Here we report a study of oxygen isotopes in two basaltic meteorite suites, the
      HEDs (howardites, eucrites and diogenites, which are thought to sample the
      asteroid 4 Vesta) and the angrites (from an unidentified asteroidal source). Our
      results demonstrate that these meteorite suites formed during early, global-scale
      melting (> or = 50 per cent) events. We show that magma oceans were present on
      all the differentiated Solar System bodies so far sampled. Magma oceans produced
      compositionally layered planetesimals; the modification of such bodies before
      incorporation into larger objects can explain some anomalous planetary features,
      such as Earth's high Mg/Si ratio.

PMID- 15959508
TI  - Nucleotide-dependent bending flexibility of tubulin regulates microtubule
      assembly.
AB  - The atomic structure of tubulin in a polymerized, straight protofilament is
      clearly distinct from that in a curved conformation bound to a cellular
      depolymerizer. The nucleotide contents are identical, and in both cases the
      conformation of the GTP-containing, intra-dimer interface is indistinguishable
      from the GDP-containing, inter-dimer contact. Here we present two structures
      corresponding to the start and end points in the microtubule polymerization and
      hydrolysis cycles that illustrate the consequences of nucleotide state on
      longitudinal and lateral assembly. In the absence of depolymerizers, GDP-bound
      tubulin shows distinctive intra-dimer and inter-dimer interactions and thus
      distinguishes the GTP and GDP interfaces. A cold-stable tubulin polymer with the
      non-hydrolysable GTP analogue GMPCPP, containing semi-conserved lateral
      interactions, supports a model in which the straightening of longitudinal
      interfaces happens sequentially, starting with a conformational change after GTP
      binding that straightens the dimer enough for the formation of lateral contacts
      into a non-tubular intermediate. Closure into a microtubule does not require GTP
      hydrolysis.

PMID- 15959510
TI  - High-frequency acoustic waves are not sufficient to heat the solar chromosphere.
AB  - One of the main unanswered questions in solar physics is why the Sun's outer
      atmosphere is hotter than its surface. Theory predicts abundant production of
      high-frequency (10-50 mHz) acoustic waves in subsurface layers of the Sun, and
      such waves are believed by many to constitute the dominant heating mechanism of
      the chromosphere (the lower part of the outer solar atmosphere) in non-magnetic
      regions. Such high-frequency waves are difficult to detect because of high
      frequency disturbances in Earth's atmosphere (seeing) and other factors. Here we
      report the detection of high-frequency waves, and we use numerical simulations to
      show that the acoustic energy flux of these waves is too low, by a factor of at
      least ten, to balance the radiative losses in the solar chromosphere. Acoustic
      waves therefore cannot constitute the dominant heating mechanism of the solar
      chromosphere.

PMID- 15959511
TI  - 'Magic' nucleus 42Si.
AB  - Nuclear shell structures--the distribution of the quantum states of individual
      protons and neutrons--provide one of our most important guides for understanding
      the stability of atomic nuclei. Nuclei with 'magic numbers' of protons and/or
      neutrons (corresponding to closed shells of strongly bound nucleons) are
      particularly stable. Whether the major shell closures and magic numbers change in
      very neutron-rich nuclei (potentially causing shape deformations) is a
      fundamental, and at present open, question. A unique opportunity to study these
      shell effects is offered by the 42Si nucleus, which has 28 neutrons--a magic
      number in stable nuclei--and 14 protons. This nucleus has a 12-neutron excess
      over the heaviest stable silicon nuclide, and has only one neutron fewer than the
      heaviest silicon nuclide observed so far. Here we report measurements of 42Si and
      two neighbouring nuclei using a technique involving one- and two-nucleon knockout
      from beams of exotic nuclei. We present strong evidence for a well-developed
      proton subshell closure at Z = 14 (14 protons), the near degeneracy of two
      different (s(1/2) and d(3/2)) proton orbits in the vicinity of 42Si, and a nearly
      spherical shape for 42Si.

PMID- 15959512
TI  - The breakdown of continuum models for mechanical contacts.
AB  - Forces acting within the area of atomic contact between surfaces play a central
      role in friction and adhesion. Such forces are traditionally calculated using
      continuum contact mechanics, which is known to break down as the contact radius
      approaches atomic dimensions. Yet contact mechanics is being applied at ever
      smaller lengths, driven by interest in shrinking devices to nanometre scales,
      creating nanostructured materials with optimized mechanical properties, and
      understanding the molecular origins of macroscopic friction and adhesion. Here we
      use molecular simulations to test the limits of contact mechanics under ideal
      conditions. Our findings indicate that atomic discreteness within the bulk of the
      solids does not have a significant effect, but that the atomic-scale surface
      roughness that is always produced by discrete atoms leads to dramatic deviations
      from continuum theory. Contact areas and stresses may be changed by a factor of
      two, whereas friction and lateral contact stiffness change by an order of
      magnitude. These variations are likely to affect continuum predictions for many
      macroscopic rough surfaces, where studies show that the total contact area is
      broken up into many separate regions with very small mean radius.

PMID- 15959513
TI  - Cortical growth marks reveal extended juvenile development in New Zealand moa.
AB  - Cyclical growth marks in cortical bone, deposited before attainment of adult body
      size, reflect osteogenetic changes caused by annual rhythms and are a general
      phenomenon in non-avian ectothermic and endothermic tetrapods. However, the
      growth periods of ornithurines (the theropod group including all modern birds)
      are usually apomorphically shortened to less than a year, so annual growth marks
      are almost unknown in this group. Here we show that cortical growth marks are
      frequent in long bones of New Zealand's moa (Aves: Dinornithiformes), a recently
      extinct ratite order. Moa showed the exaggerated K-selected life-history strategy
      formerly common in the New Zealand avifauna, and in some instances took almost a
      decade to attain skeletal maturity. This indicates that reproductive maturity in
      moa was extremely delayed relative to all extant birds. The two presently
      recognized moa families (Dinornithidae and Emeidae) also showed different
      postnatal growth rates, which were associated with their relative differences in
      body size. Both species of giant Dinornis moa attained their massive stature (up
      to 240 kg live mass) by accelerating their juvenile growth rate compared to the
      smaller emeid moa species, rather than by extending the skeletal growth period.

PMID- 15959514
TI  - The initiation of liver development is dependent on Foxa transcription factors.
AB  - The specification of the vertebrate liver is thought to occur in a two-step
      process, beginning with the establishment of competence within the foregut
      endoderm for responding to organ-specific signals, followed by the induction of
      liver-specific genes. On the basis of expression and in vitro studies, it has
      been proposed that the Foxa transcription factors establish competence by opening
      compacted chromatin structures within liver-specific target genes. Here we show
      that Foxa1 and Foxa2 (forkhead box proteins A1 and A2) are required in concert
      for hepatic specification in mouse. In embryos deficient for both genes in the
      foregut endoderm, no liver bud is evident and expression of the hepatoblast
      marker alpha-fetoprotein (Afp) is lost. Furthermore, Foxa1/Foxa2-deficient
      endoderm cultured in the presence of exogenous fibroblast growth factor 2 (FGF2)
      fails to initiate expression of the liver markers albumin and transthyretin.
      Thus, Foxa1 and Foxa2 are required for the establishment of competence within the
      foregut endoderm and the onset of hepatogenesis.

PMID- 15959515
TI  - Notch/gamma-secretase inhibition turns proliferative cells in intestinal crypts
      and adenomas into goblet cells.
AB  - The self-renewing epithelium of the small intestine is ordered into
      stem/progenitor crypt compartments and differentiated villus compartments. Recent
      evidence indicates that the Wnt cascade is the dominant force in controlling cell
      fate along the crypt-villus axis. Here we show a rapid, massive conversion of
      proliferative crypt cells into post-mitotic goblet cells after conditional
      removal of the common Notch pathway transcription factor CSL/RBP-J. We obtained a
      similar phenotype by blocking the Notch cascade with a gamma-secretase inhibitor.
      The inhibitor also induced goblet cell differentiation in adenomas in mice
      carrying a mutation of the Apc tumour suppressor gene. Thus, maintenance of
      undifferentiated, proliferative cells in crypts and adenomas requires the
      concerted activation of the Notch and Wnt cascades. Our data indicate that gamma
      secretase inhibitors, developed for Alzheimer's disease, might be of therapeutic
      benefit in colorectal neoplastic disease.

PMID- 15959516
TI  - Notch signals control the fate of immature progenitor cells in the intestine.
AB  - The Notch signalling pathway plays a crucial role in specifying cellular fates in
      metazoan development by regulating communication between adjacent cells.
      Correlative studies suggested an involvement of Notch in intestinal development.
      Here, by modulating Notch activity in the mouse intestine, we directly implicate
      Notch signals in intestinal cell lineage specification. We also show that Notch
      activation is capable of amplifying the intestinal progenitor pool while
      inhibiting cell differentiation. We conclude that Notch activity is required for
      the maintenance of proliferating crypt cells in the intestinal epithelium.

PMID- 15959518
TI  - Crystal structure of thymine DNA glycosylase conjugated to SUMO-1.
AB  - Members of the small ubiquitin-like modifier (SUMO) family can be covalently
      attached to the lysine residue of a target protein through an enzymatic pathway
      similar to that used in ubiquitin conjugation, and are involved in various
      cellular events that do not rely on degradative signalling via the proteasome or
      lysosome. However, little is known about the molecular mechanisms of SUMO
      modification-induced protein functional transfer. During DNA mismatch repair,
      SUMO conjugation of the uracil/thymine DNA glycosylase TDG promotes the release
      of TDG from the abasic (AP) site created after base excision, and coordinates its
      transfer to AP endonuclease 1, which catalyses the next step in the repair
      pathway. Here we report the crystal structure of the central region of human TDG
      conjugated to SUMO-1 at 2.1 A resolution. The structure reveals a helix
      protruding from the protein surface, which presumably interferes with the product
      DNA and thus promotes the dissociation of TDG from the DNA molecule. This helix
      is formed by covalent and non-covalent contacts between TDG and SUMO-1. The non
      covalent contacts are also essential for release from the product DNA, as
      verified by mutagenesis.

PMID- 15959517
TI  - In vivo imaging of specialized bone marrow endothelial microdomains for tumour
      engraftment.
AB  - The organization of cellular niches is known to have a key role in regulating
      normal stem cell differentiation and regeneration, but relatively little is known
      about the architecture of microenvironments that support malignant metastasis.
      Using dynamic in vivo confocal imaging, here we show that murine bone marrow
      contains unique anatomic regions defined by specialized endothelium. This
      vasculature expresses the adhesion molecule E-selectin and the chemoattractant
      stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that
      influence the homing of a variety of tumour cell lines. Disruption of the
      interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6
      cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further
      studies revealed that circulating leukaemic cells can engraft around these
      vessels, suggesting that this molecularly distinct vasculature demarcates a
      microenvironment for early metastatic tumour spread in bone marrow. Finally,
      purified haematopoietic stem/progenitor cells and lymphocytes also localize to
      the same microdomains, indicating that this vasculature might also function in
      benign states to demarcate specific portals for the entry of cells into the
      marrow space. Specialized vascular structures therefore appear to delineate a
      microenvironment with unique physiology that can be exploited by circulating
      malignant cells.

PMID- 15959519
TI  - Structural basis for the promiscuous biosynthetic prenylation of aromatic natural
      products.
AB  - The anti-oxidant naphterpin is a natural product containing a polyketide-based
      aromatic core with an attached 10-carbon geranyl group derived from isoprenoid
      (terpene) metabolism. Hybrid natural products such as naphterpin that contain 5
      carbon (dimethylallyl), 10-carbon (geranyl) or 15-carbon (farnesyl) isoprenoid
      chains possess biological activities distinct from their non-prenylated aromatic
      precursors. These hybrid natural products represent new anti-microbial, anti
      oxidant, anti-inflammatory, anti-viral and anti-cancer compounds. A small number
      of aromatic prenyltransferases (PTases) responsible for prenyl group attachment
      have only recently been isolated and characterized. Here we report the gene
      identification, biochemical characterization and high-resolution X-ray crystal
      structures of an architecturally novel aromatic PTase, Orf2 from Streptomyces sp.
      strain CL190, with substrates and substrate analogues bound. In vivo, Orf2
      attaches a geranyl group to a 1,3,6,8-tetrahydroxynaphthalene-derived polyketide
      during naphterpin biosynthesis. In vitro, Orf2 catalyses carbon-carbon-based and
      carbon-oxygen-based prenylation of a diverse collection of hydroxyl-containing
      aromatic acceptors of synthetic, microbial and plant origin. These crystal
      structures, coupled with in vitro assays, provide a basis for understanding and
      potentially manipulating the regio-specific prenylation of aromatic small
      molecules using this structurally unique family of aromatic PTases.

PMID- 15959520
TI  - Genomics: big tasks for small molecules.

PMID- 15959521
TI  - Genomics: getting down to details.

PMID- 15959522
TI  - Genomics: genotyping gets up to speed.

PMID- 15959523
TI  - Genomics: SNPs and human disease.

PMID- 15959525
TI  - A global view.

PMID- 15959526
TI  - An eastern promise of regeneration.

PMID- 15959527
TI  - Damned if you don't.

PMID- 15959528
TI  - Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase
      domain mutations for acute myeloid leukemia: a meta-analysis.
AB  - Two distinct forms of fms-like tyrosine kinase (FLT3) gene aberrations, internal
      tandem duplication (ITD) and tyrosine kinase domain (TKD) mutations, have been
      recognized in a substantial proportion of patients with acute myeloid leukemia
      (AML). To investigate their prognostic significance, we performed a meta-analysis
      of the four published studies that provided survival information according to the
      FLT3 status: ITD, TKD mutation, and wild type. The summary hazard ratios for
      disease-free survival (DFS) were 1.88 (95% confidence interval (CI) 1.58-2.23;
      P<0.001) for FLT3 mutations, 1.86 (95% CI: 1.52-2.29; P<0.001) for ITD, and 1.90
      (95% CI: 1.40-2.60; P<0.001) for TKD mutation. The corresponding ratios for
      overall survival were 1.61 (95% CI: 1.37-1.89; P<0.001), 1.68 (95% CI: 1.39-2.03;
      P<0.001), and 1.37 (95% CI: 0.94-2.01; P=0.104). Neither white blood cell count
      at diagnosis nor cytogenetic risk category was a significant source of
      heterogeneity. These findings indicate that FLT3 mutations have an adverse effect
      on the outcome for AML, and that the negative impact of TKD mutation seems
      comparable to that of ITD with regard to DFS. Although it should be borne in mind
      that this meta-analysis was based on data abstracted from observational studies,
      these results may justify the risk-adapted therapeutic strategies for AML
      according to the FLT3 status.

PMID- 15959529
TI  - VEGF-induced survival of chronic lymphocytic leukemia is independent of Bcl-2
      phosphorylation.

PMID- 15959530
TI  - Multiple myeloma oncogene 1 (MUM1)/interferon regulatory factor 4 (IRF4)
      upregulates monokine induced by interferon-gamma (MIG) gene expression in B-cell
      malignancy.
AB  - MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) is a
      transcription factor that is activated as a result of t(6;14)(p25;q32) in
      multiple myeloma. MUM1 expression is seen in various B-cell lymphomas and
      predicts an unfavorable outcome in some lymphoma subtypes. To elucidate its role
      in B-cell malignancies, we prepared MUM1-expressing Ba/F3 cells, which
      proliferated until higher cellular density than the parental cells, and performed
      cDNA microarray analysis to identify genes whose expression is regulated by MUM1.
      We found that the expression of four genes including FK506-binding protein 3
      (FKBP3), the monokine induced by interferon-gamma(MIG), Fas apoptotic inhibitory
      molecule (Faim) and Zinc-finger protein 94 was altered in the MUM1-expressing
      cells. We then focused on MIG since its expression was immediately upregulated by
      MUM1. In reporter assays, MUM1 activated the MIG promoter in cooperation with
      PU.1, and the interaction between MUM1 and the MIG promoter sequence was
      confirmed. The expression of MIG was correlated with that of MUM1 in B-CLL cell
      lines, and treatment with neutralizing antibodies against MIG and its receptor,
      CXCR3, slightly inhibited the proliferation of two MUM1-expressing lines. These
      results suggest that MUM1 plays roles in the progression of B-cell
      lymphoma/leukemia by regulating the expression of various genes including MIG.
      Leukemia (2005) 19, 1471-1478. doi:10.1038/sj.leu.2403833; published online 16
      June 2005.

PMID- 15959531
TI  - Dlk1 in normal and abnormal hematopoiesis.
AB  - Dlk1 (Pref-1) is a transmembrane and secreted protein, which is a member of the
      epidermal growth factor-like family, homologous to Notch/Delta/Serrate. We have
      found by real-time RT-PCR that Dlk1 mRNA levels were high in CD34(+) cells in 10
      of 12 MDS samples compared with CD34(+) cells from 11 normals. Also, Dlk1 mRNA
      was elevated in mononuclear, low density bone marrow cells from 11/38 MDS
      patients, 5/11 AML M6 and 2/4 AML M7 samples. Furthermore, 5/6 erythroleukemia
      and 2/2 megakaryocytic leukemia cell lines highly expressed Dlk1 mRNA. Levels of
      Dlk1 mRNA markedly increased during megakaryocytic differentiation of both CMK
      megakaryoblasts as well as normal CD34(+) hematopoietic stem cells. High serum
      levels of Dlk1 occurred in RA (4/10) and essential thrombocythemia (2/10)
      patients. Functional studies showed that forced expression of Dlk1 enhanced
      proliferation of K562 cells growing in 1% fetal bovine serum. Analysis of
      hematopoiesis of Dlk1 knockout mice suggested that Dlk1 contributed to
      granulocyte, megakaryocyte and B-cell clonogenic growth and was needed for
      generation of splenic B-cells. In summary, Dlk1 is overexpressed in selected
      samples of MDS (especially RA and RAEB) and AML (particularly M6, M7), and it
      appears to be associated with normal development of megakaryocytes and B cells.

PMID- 15959532
TI  - Efficient engraftment of primary adult T-cell leukemia cells in newborn
      NOD/SCID/beta2-microglobulin(null) mice.
AB  - Adult T-cell leukemia (ATL) develops via multiple oncogenic steps in human T-cell
      leukemia virus type I (HTLV-I) carriers. To better understand pathogenesis of
      ATL, we developed a novel xenogeneic engraftment model in which primary ATL cells
      are intravenously transplanted into neonatal nonobese diabetic (NOD)/severe
      combined immunodeficiency (SCID)/beta2-microglobulin(null)
      (NOD/SCID/beta2m(null)) mice. Acute-type ATL cells engrafted in the peripheral
      blood and in the lymph nodes of recipients at a high efficiency. Engrafted ATL
      cells were dually positive for human CD4 and CD25, and displayed patterns of HTLV
      I integration identical to those of donors by Southern blot analysis. These cells
      infiltrated into recipients' liver, and formed nodular lesions, recapitulating
      the clinical feature of each patient. In contrast, in smoldering-type ATL cases,
      multiple clones of ATL cells engrafted efficiently in NOD/SCID/beta2m(null) mice.
      When smoldering-type ATL cells were retransplanted into secondary
      NOD/SCID/beta2m(null) recipients, single HTLV-I-infected clones became
      predominant, suggesting that clones with dominant proliferative activity can be
      competitively selected in this xenogeneic system. Taken together, the
      NOD/SCID/beta2m(null) newborn system is useful to understand kinetics,
      metastasis, and disease progression of ATL in vivo.

PMID- 15959533
TI  - CD45 expression by bone marrow plasma cells in multiple myeloma: clinical and
      biological correlations.
AB  - Multiple myeloma (MM) is characterized by accumulation of clonal plasma cells
      (PCs). CD45, a key regulator of antigen-mediated signaling and activation in
      lymphocytes, is present in early stages of PCs development. We studied CD45
      expression on MM PCs by flow cytometry, correlating it to important biological
      disease characteristics. Additionally, we examined the expression of various
      adhesion molecules on PCs. A total of 75 patients with untreated MM (29),
      relapsed MM (17), smoldering MM (12), and monoclonal gammopathy of undetermined
      significance (MGUS) (17) were studied. The proportion of PCs expressing CD45 was
      higher among those with early disease (MGUS or smoldering MM) compared to those
      with advanced disease (new or relapsed MM) (43 vs 22%; P=0.005). Among those with
      advanced disease, patients with bone lesions had a lower percentage of CD45
      positive (CD45+) PCs; 14 vs 34% (P=0.02). Patients with high-grade angiogenesis
      had a lower percentage of CD45+ PCs; 13 vs 31% (P=0.03). The median overall
      survival for the CD45+ group (>20% PCs positive) was 39 vs 18 months for the CD45
      negative (CD45-) group (P=0.07). The expression of CD138, CD56 and CD54 were
      higher among the CD45- PCs. This study demonstrates important biological
      correlates of CD45 expression on myeloma cells.

PMID- 15959534
TI  - IL-24 inhibits the growth of hepatoma cells in vivo.
AB  - The interleukin (IL)-24/melanoma differentiation associated gene-7 (mda-7) is a
      member of the IL-10 cytokine family. Introduction of the IL-24 gene into a
      variety of cancer cells suppresses their growth. It has not been shown, however,
      whether IL-24 can suppress the growth of hepatoma cells. The purpose of this
      study was to determine whether the mouse (m)IL-24 gene would suppress hepatoma
      cells in vivo after being delivered via intramuscular electroporation. After mice
      were given a subcutaneous dorsal injection of ML-1 hepatoma cells, the mIL-24
      gene was delivered and suppressed tumor growth. On day 140, 60% of the mIL-24
      treated mice (n=10) and 0% (n=10) of the untreated control mice had survived. We
      also generated a mouse-hepatoma model by injecting ML-1 cells into the spleen,
      which resulted in tumor metastasis in the liver. Intramuscular electroporation of
      mIL-24 also inhibited hepatoma-cell growth in the liver. On day 50, 90% of the
      experimental mice (n=10) and 40% (n=10) of the control mice had survived. Liver
      tumors in surviving experimental mice were 50% smaller than those in control
      mice. IL-24 also inhibited tumor vascularization. These results suggest that IL
      24 has potential therapeutic value for hepatoma

PMID- 15959535
TI  - PDCD1: a tissue-specific susceptibility locus for inherited inflammatory
      disorders.
AB  - Variation in genes encoding costimulatory molecules expressed on lymphocytes has
      been expected to contribute to the genetic component of inflammatory disease, but
      only the gene encoding the inhibitory protein, CTLA-4, seems consistently to
      confer disease susceptibility. Studies in murine models implicate the inhibitory
      product of the pd1 gene, programmed death-1, in the maintenance of peripheral
      tolerance to self-antigens. We identify 22 single-nucleotide polymorphisms (SNPs)
      in the equivalent human gene, PDCD1, a number of which show significant
      associations with the specific immunoglobulin E response to grass allergens in
      atopic individuals. Stepwise analyses indicate that four of the disease
      associated SNPs have independent effects. The two most common haplotypes show
      positive and negative associations but rarer haplotypes are also likely to be of
      influence. In a case-control study, multiple regression analysis of genotypic
      data implies that PDCD1 also confers susceptibility to rheumatoid arthritis.
      Along with work linking PDCD1 with susceptibility to another autoimmune
      condition, systemic lupus erythematosus, our data identify PDCD1 as a second
      immunomodulatory gene with pleiotropic effects in human disease. Genes encoding
      negative regulators may generally confer a significant fraction of the genetic
      risk associated with inherited inflammatory disorders.

PMID- 15959536
TI  - Prognostic significance of blood pressure measured in the office, at home and
      during ambulatory monitoring in older patients in general practice.
AB  - The purpose of the study was to assess the prognostic significance of out-of-the
      office blood pressure (BP) measurement in older patients in general practice, and
      to compare the results for BP measured in the office, at home and during 24-h
      ambulatory monitoring. All registerd patients who were 60 years or older were
      eligible for the study, except when bedridden, demented or admitted in a home for
      sick elderly people, or when they had suffered a myocardial infarction or stroke.
      After baseline measurements in 1990-1993, incidence of major cardiovascular
      events (cardiovascular death, myocardial infarction and stroke) was ascertained
      in 2002-2003 and related to the BPs by use of multivariate Cox regression
      analysis. Age of the 391 patients averaged 71+/-9 years; 40% were men. During
      median follow-up of 10.9 years, 86 patients (22%) suffered a cardiovascular
      event. The adjusted relative hazard rate, associated with a 1 s.d. increment in
      systolic BP was 1.13 for office BP (NS), and, respectively, 1.32, 1.33 and 1.42,
      for home, daytime and night time BP (P< or =0.01 for all). Results were similar
      for diastolic BP. The prognostic significance of all out-of-the-office BPs was
      independent of office BP. The prognostic value of home BP was equal to (systolic)
      or even better (diastolic) than that of daytime BP. Night time BP predicted
      cardiovascular events independent of all other BPs. Prognosis of white-coat
      hypertension was similar to that of true normotension, but better than in
      sustained hypertension. In conclusion, the prognostic value of home BP is better
      than that of office BP in older patients in primary care, and is at least equal
      to that of daytime ambulatory BP. The prognosis of patients with white-coat
      hypertension is similar to that of true normotensives.

PMID- 15959537
TI  - Time of day for exercise on blood pressure reduction in dipping and nondipping
      hypertension.
AB  - Time of day (TOD) for exercise may influence blood pressure (BP) reduction in
      hypertension because of the diurnal variation of BP and the duration of BP
      reduction following a single bout of exercise. The purpose of this study was to
      observe the effects of TOD for exercise on ambulatory blood pressure reduction in
      dipping (n=5) and nondipping (n=9) hypertension (<10% drop in nighttime BP
      (BP(night))). HYPOTHESES: (1) evening exercise (PM(ex)) would exhibit a greater
      BP(night) reduction in Non-Dippers than Dippers, (2) morning exercise (AM(ex))
      would exhibit similar daytime BP (BP(day)) reduction in Dippers and Non-Dippers,
      (3) AM(ex) would exhibit greater 24 h BP (BP(24 h)) reduction than PM(ex) in
      Dippers, and (4) AM(ex) and PM(ex) would exhibit similar BP(24 h) reduction in
      Non-Dippers. BP responses to AM(ex) (0600-0800 h; 30 min at 50% VO(2peak)) and
      PM(ex) (1700-1900 h) were compared to each control day in a randomized design.
      Systolic (S) and diastolic (D) BP were averaged for BP(24 h), BP(day), and
      BP(night). A two-way ANOVA (dipping X time of exercise) using BP reduction with
      repeated measures were performed at P<0.05. FINDINGS: (1) Non-Dippers respond to
      exercise despite of TOD for exercise, (2) PM(ex) exhibited a greater SBP(night)
      reduction in Non-Dippers than Dippers, (3) AM(ex) exhibited similar SBP(day)
      reductions in Dippers and Non-Dippers, and (4) AM(ex) and PM(ex) exhibited
      similar SBP(24 h) reduction in Dippers and Non-Dippers. Dippers and Non-Dippers
      respond differently to TOD for exercise. The duration of the BP reduction
      persists up to 24 h after exercise.

PMID- 15959539
TI  - Taming TRAIL: the winding path to a novel form of cancer therapy.

PMID- 15959545
TI  - Re-operation for the treatment of well differentiated thyroid cancer: necessity,
      safety and impaction on further management.
AB  - BACKGROUND: The diagnosis of thyroid carcinoma during the course of lobectomy for
      a dominant nodule occasionally cannot be rendered on the basis of frozen section.
      Once the diagnosis of carcinoma is made, the question of completion thyroidectomy
      arises. PATIENTS AND METHODS: During a period of 3 years, 28 patients diagnosed
      with well-differentiated thyroid cancer (WDTC), and operated upon with less than
      total thyroidectomy, were admitted to our department. Patients had no clinical or
      radiological evidence of any residual disease at the time of admission. All were
      submitted for total thyroidectomy. RESULTS: There were 7 men and 21 women (1:3),
      and the average age was 38.6+/-1.3 years (range, 20 to 62 years). The
      postoperative morbidity in completion thyroidectomy consisted of transient
      hypoparathyroidism in 2 patients (7.1 %), permanent hypoparathyroidism in 1
      patient (3.5%), there was no recurrent laryngeal nerve palsy, there were
      haematoma in 2 patients, and seroma in 1 patient. Completion thyroidectomy
      resulted in detecting 9 patients (32.1%) having residual disease that was not
      clinically manifest. CONCLUSION: Although many surgeons advocate total or near
      total thyroidectomy for differentiated thyroid carcinoma, some of these surgeons
      hesitate to complete thyroidectomy after lobectomy for thyroid nodule when there
      is no clinical evidence to suggest bilateral disease, for fear of added morbidity
      to the patients. However, as demonstrated in this study, completion thyroidectomy
      was shown to be a fairly safe procedure, which carries a low incidence of
      complications. It also facilitates further management and follow-up with
      radioactive iodine. The decision to perform completion thyroidectomy for WDTC
      should be based on the patient's risk category, and not on a concern for risk of
      complications from the second procedure.

PMID- 15959546
TI  - Predictors of outcome after radical cystectomy for bladder cancer in saudi
      patients; single institution experience.
AB  - AIM OF THE STUDY: To evaluate different prognostic factors that may affect
      disease-specific survival in patients with bladder cancer following radical
      cystectomy. METHODS: Between July 1975 and December 2000, 229 patients underwent
      radical cystectomy and urinary diversion for bladder cancer in King Faisal
      Specialist Hospital and Research Center (KFSH & RC), Riyadh, Saudi Arabia. 175
      patients had available records for review. Retrospective chart review was done.
      Demographic, clinical and pathological variables which may affect disease
      specific survival in bladder cancer patients were pooled. Univariate and
      multivariate analyses were done with disease specific survival as an end point.
      RESULTS: Our patients were 140 males (80%) and 35 females (20%). Their mean age
      was 54 years (range: 21-90 years). The median follow-up period was 1.5 years
      (range: one month-19 years). Five-year disease specific survival was 44%. On
      univariate analysis, patients' age, lymph node status, pathological staging and
      presence of hydronephrosis were significant predictors of disease specific
      survival. However, only lymph node status (p<0.0001), pathological staging
      (p=0.0411) & presence of hydronephrosis (p=0.0264) were significant predictors of
      disease specific survival in multivariate analysis. CONCLUSION: Pathological
      stage, lymph node status and upper obstructive uropathy are significant
      prognostic factors in bladder cancer patients after radical cystectomy. These
      factors may help to define bladder cancer patient groups who require further
      therapy or enrollment in controlled trials to investigate additional therapy.

PMID- 15959547
TI  - Surgical management for giant cell tumor of bones.
AB  - PURPOSE: To evaluate the different surgical techniques used in the treatment of
      giant cell tumor of bone and their effect on the rate of local recurrence.
      PATIENTS AND METHODS: This is a prospective study of fifty-two patients with
      giant cell tumor (GCT) of the bones treated at the National Cancer Institute,
      Cairo University between 1998 and 2002. All patients were evaluated by clinical
      examination, plain X-ray, CT scan and MRI (in some cases). Biopsy was taken in
      all cases to confirm the diagnosis and to define the grade of the tumor. All
      patients underwent surgical treatment including curettage, curettage combined
      with cryosurgery and bone cement or bone graft, bone resection and amputation.
      Selection of the surgical technique was based on site and size of the lesion,
      soft tissue involvement (intra- or extra-compartmental), tumor grade and if
      recurrent or not. Patients were followed up for a minimum of twenty-four months.
      RESULTS: Out of 52 patients 14 patients were males and 38 patients were females,
      (male to female ratio was (1: 2.7). The age of our patients ranged from 13 to 71
      years, with a mean age of 32.9 years. Based on Enneking's staging system, 40
      patients (77%) were stage IA, 9 patients (17%) were stage IB & 3 were stage IIB.
      Histopathological examination of all cases revealed giant cell tumor of
      borderline malignancy. Curettage alone was done in 4 patients, curettage and bone
      cement in 7 patients, curettage, cryosurgery and bone graft in 4 patients,
      curettage, cryosurgery and bone cement in 18 patients, resection in 16 patients
      and amputation in 3 patients. There were no mortalities among our cases. Local
      recurrence was highest in cases treated with curettage only (50%), lowest in
      cases treated with curettage and cryosurgery with bone cement (16.6%).
      CONCLUSION: The main primary treatment of GCT is surgery; the type of which
      depends on preoperative evaluation, which includes clinical evaluation that
      involves the site and size of the tumor in relation to surrounding structures,
      together with plain X-ray, CT scan and/or MRI as indicated, and tissue biopsy to
      define tumor grade. Curettage alone results in high rate of local recurrence. On
      the other hand, curettage and adjuvant cryosurgery using bone cement or bone
      grafts give low rate of local recurrence. Resection is recommended for stages IB
      and IIB, extremely large lesions, and in cases where resection results in no
      significant morbidity as proximal fibula and flat bones. Amputation is preserved
      for massive recurrences and malignant transformation.

PMID- 15959548
TI  - Dexmedetomidine vs. propofol for short-term sedation of postoperative
      mechanically ventilated patients.
AB  - BACKGROUND: Propofol is often used for sedation in the intensive care unit. The
      aim of this study was to compare the efficacy and endocrine response of propofol
      vs. the new alpha2-agonist dexmedetomidine for sedation in surgical intensive
      care patients who need postoperative short-term ventilation. METHODS: Our work is
      a randomized clinical study conducted on sixty adult patients who required
      postoperative short term ventilation and sedation. The patients were allocated
      randomly, to receive IV infusion of either dexmedetomidine 0.2-0.5 microg/kg/h or
      propofol 0.5-1 mg/kg/h. Hemodynamic parameters, Ramsay sedation score, extubation
      time and serum cortisol and interleukin-6 (IL-6) levels were measured. RESULTS:
      Ramsay sedation score was 4.1+/-1 and 4+/-0.9 for propofol and dexmedetomidine,
      respectively, (p=0.59.) Total fentanyl dose in the propofol group was 75+/-15
      microg compared to 15+/-10.5 microg in the dexmedetomidine group, (p=0.0045).
      Patients who received dexmedetomidine infusion had significantly lower heart
      rates compared to patients who received propofol infusion, (p=0.041). Pre
      infusion serum concentrations of IL-6 were comparable in both groups, while the
      24 h post-infusion levels were insignificantly decreased in both groups compared
      to pre-infusion level, (p=0.36). There were no intergroup differences in serum
      cortisol concentrations (p=0.231). CONCLUSIONS: Dexmedetomidine and propofol are
      safe sedative drugs for postoperative mechanichally ventilated patients. Patients
      were easily aroused to co-operate without showing signs of irritations with less
      fentanyl analgesia in the dexmedetomidine group. Dexmedetomidine and propofol do
      not inhibit adrenal function, but they may influence the inflammatory response.

PMID- 15959549
TI  - Predictive value of thymidine phosphorylase in gastric carcinoma.
AB  - BACKGROUND AND PURPOSE: Thymidine Phosphorylase/ Platelet Derived-Endothelial
      Cell Growth Factor (TP/PD-ECGF) has an angiogenic and chemotherapeutic effects.
      The aim of this work was to evaluate TP/PD-ECGF expression in gastric
      adenocarcinoma and find its correlation with established clinicopathological
      parameters and patients' survival. MATERIALS AND METHODS: Samples studied
      consisted of fifty-two gastric specimens (27 cases of chronic gastritis and 25
      cases of malignant adenocarcinoma). Immunohistochemical staining for TP/PD-ECGF
      was done and the tumor was considered positive when more than 5% of cells showed
      positive staining. RESULTS: TP/PD-ECGF expression was significantly higher in the
      malignant group when compared to the control group (p = 0.001). Tumor and stromal
      cell TP/PD-ECGF expression in the malignant group was significantly correlated
      with size of the tumor, mitotic count, stage grouping, depth of invasion, number
      of lymph nodes (LN) involved, perineural invasion, lymphoplasmacytic and tumor
      associated macrophages (TAMs) infiltration and vessel density (VD). Furthermore,
      stromal expression of TP/PD-ECGF was significantly correlated with postoperative
      chemotherapy and apoptotic count. Survival analysis revealed that proximal tumor,
      small size, early stage, negative LN metastasis, absence of perineural invasion,
      low VD and negative tumor and stromal TP/PD-ECGF expression correlated with
      better patients' survival. CONCLUSIONS: TP/PD-ECGF might have an angiogenic
      function and role in tumor growth, invasion and metastasis. TP/PD-ECGF could
      enhance the effect of postoperative chemotherapy.

PMID- 15959550
TI  - Expression of matrix metalloproteinase-2 in renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a family of carcinomas arising from the
      renal tubular epithelium through different genetic lesions. The most common
      characterstics of RCC are hypervascularity, tendency to metastasize widely before
      giving rise to any symptoms or signs, and poor prognosis. It has been reported
      that matrix metallopropteinases (MMPs) are a family of endopeptidases implicated
      in tissue remodeling and cancer invasion. Therefore, the aim of the present study
      was to investigate the expression of MMP-2 in RCC and correlate its expression
      with the clinicopathologic prognostic parameters. MATERIAL AND METHODS: Fifty
      cases of primary RCC comprised the material of this study. Formalin-fixed
      paraffin-embedded tissues were stained with MMP-2 immunostaining, using improved
      streptavidin-biotin amplified system. The intensity of staining and percentage of
      positive cells were assessed. RESULTS: MMP-2 was expressed as diffuse brown
      cytoplasmic staining in positive cells. The non-tumorous renal tissue showed
      negative staining whereas the tumor cells, fibroblasts and vascular endothelial
      cells showed immunoreactivity in positive cases. 43/50 RCC cases studied were
      positive for MMP-2. A positive correlation was observed between MMP-2 expression
      and tumor size, histologic type, capsular & vascular invasion and high levels of
      cellular proliferation. CONCLUSION: It seems that MMP-2 is involved in tumor
      expansion phenomena associated with tumor progression, invasion of the
      microvasculature and distant metastasis of RCC.

PMID- 15959551
TI  - Hypofractionation versus conventional fractionation radiotherapy after
      conservative treatment of breast cancer: early skin reactions and cosmetic
      results.
AB  - PURPOSE: To compare in a prospective trial the acute skin reaction and late
      cosmetic effects of normal fractionation versus hypofractionation radiotherapy
      after breast conserving surgery. PATIENTS AND METHODS: Thirty patients with T 1
      2N0M0 breast cancer who underwent breast conserving surgery (BCS) were included
      in the study. Half of the patients received whole breast irradiation, consisting
      of 50 Gy/25f/5w+boost 10Gy/5f/1w to tumor bed (group A). The other half received
      42.5Gy/16f/22 days (group B). The two groups were comparable otherwise. Early
      skin reaction and late cosmetic results were graded according to RTOG guidelines.
      RESULTS: The study showed no statistical significant difference between the two
      treatment groups as regards acute skin reactions and cosmetic appearance.
      However, the maximum skin reaction occurred 2 weeks earlier for patients within
      group B (3rd week) compared to group A (5th week). Apart from breast volume,
      there was no significant correlation between any of the patients or tumor factors
      and the incidence of acute skin reactions in either group of patients. Patients
      with large breast volume >1100cc had a higher rate and a longer duration of
      maximum skin reaction in group A (4 weeks versus 2 weeks in patients with small
      breast volume </= 1100cc), while in group B, all patients had a maximum duration
      of 4.5 weeks. This difference was not statistically significant. After median
      follow-up of 22 months, again there was no difference between the two groups as
      regard the cosmetic outcome. Lumpectomy volume and lumpectomy/breast volume ratio
      (regardless of the tumor volume) were the only factors that significantly
      affected the cosmetic appearance. CONCLUSIONS: Preliminary results support the
      use of a shorter fractionation schedule of 42.5Gy/16f/22 days in patients with
      breast conserving surgery. The study is still going on to study the late effects
      on a larger number of patients for final evaluation of this regimen.

PMID- 15959552
TI  - Pleurodesis as a palliative treatment of advanced lung cancer with malignant
      pleural effusion.
AB  - PURPOSE: This study was conducted to evaluate the success rate of management of
      advanced. Lung cancer patients with malignant pleural effusion comparing talc
      powder with tetracycline for pleurodesis. PATIENTS AND METHODS: We report 60
      patients with lung cancer associated with malignant pleural effusion treated in
      the department of surgery NCI, Cairo University, between January. 1998 and
      February, 2003. Patients were Divided Into Three Groups: Group I: Pleurodesis
      using tetracycline (20 patients). Group II: Pleurodesis using talc slurry (20
      patients). Group III: Pleurodesis using talc insufflation (20 patients). Good
      response to pleurodesis is defined as no pleural fluid re-accumulation or minimal
      pleural fluid re-accumulation not causing symptoms or requiring further
      aspiration for one month. RESULTS: There were 34 males and 26 females, mean age
      was 54 years with range of 42-66 years, right sided effusion was present in 32
      patients (53%) and left sided in 28 patients (47%). Pathological subtypes were
      adenocarcinoma in 32 patients, squamous cell carcinoma in 18 and undifferentiated
      carcinoma in 10 patients. In group I, 12 patients (60%) showed good response to
      intrapleural tetracycline, 15 patients (75%) responded in group II, while 17
      patients (85%) showed good response in group III. Post pleurodesis complications
      included, fever, chest pain and empyema. CONCLUSION: It is concluded from this
      study that thoracoscopic talc insufflation was an effective, easy and low cost
      method for producing pleurodesis in patients with recurrent malignant pleural
      effusion and proved to be better than talc slurry and tetracycline.

PMID- 15959553
TI  - MeCP2: the chromatin connection and beyond.
AB  - Of the recently discovered group of proteins that interpret DNA methylation
      signals by preferentially associating with methylated CpG dinucleotides, the
      methyl-CpG-binding protein 2 (MeCP2) has attracted considerable attention in view
      of its ability to repress transcription. The interest in MeCP2 dramatically
      increased following the discovery of mutated forms of the protein in patients
      with Rett syndrome, a neurodevelopmental disease. A connection with
      carcinogenesis has also been established. This review attempts to bring together
      and critically discuss recently acquired information about the molecular biology
      of the protein and its mechanism of action. A careful overview of the literature
      reveals the complexity of its activity, which goes well beyond the recognized
      chromatin connections. Finally, the newly established facts concerning the
      connection of MeCP2 to human disease are presented.

PMID- 15959554
TI  - Poly(ADP-ribosylation) and genomic stability.
AB  - Poly(ADP-ribose) polymerases (PARPs) catalyze the synthesis of ADP-ribose
      polymers and attach them to specific target proteins. To date, 6 members of this
      protein family in humans have been characterized. The best-known PARP, PARP-1, is
      located within the nucleus and has a major function in DNA repair but also in the
      execution of cell death pathways. Other PARP enzymes appear to carry out highly
      specific functions. Most prominently, the tankyrases modify telomere-binding
      proteins and thereby regulate telomere maintenance. Since only a single enzyme,
      poly(ADP-ribose) glycohydrolase (PARG), has been identified, which degrades
      poly(ADP-ribose), it is expected that this protein has important roles in PARP
      mediated regulatory processes. This review summarizes recent observations
      indicating that poly(ADP-ribosylation) represents a major mechanism to regulate
      genomic stability both when DNA is damaged by exogenous agents and during cell
      division.

PMID- 15959555
TI  - An epigenetic code for DNA damage repair pathways?
AB  - Exposure of living cells to intracellular or external mutagens results in DNA
      damage. Accumulation of DNA damage can lead to serious consequences because of
      the deleterious mutation rate resulting in genomic instability, cellular
      senescence, and cell death. To counteract genotoxic stress, cells have developed
      several strategies to detect defects in DNA structure. The eukaryotic genomic DNA
      is packaged through histone and nonhistone proteins into a highly condensed
      structure termed chromatin. Therefore the cellular enzymatic machineries
      responsible for DNA replication, recombination, and repair must circumvent this
      natural barrier in order to gain access to the DNA. Several studies have
      demonstrated that histone/chromatin modifications such as acetylation,
      methylation, and phosphorylation play crucial roles in DNA repair processes. This
      review will summarize the recent data that suggest a regulatory role of the
      epigenetic code in DNA repair processes. We will mainly focus on different
      covalent reversible modifications of histones as an initial step in early
      response to DNA damage and subsequent DNA repair. Special focus on a potential
      epigenetic histone code for these processes will be given in the last section. We
      also discuss new technologies and strategies to elucidate the putative epigenetic
      code for each of the DNA repair processes discussed.

PMID- 15959556
TI  - Epigenetic regulation of lymphoid specific gene sets.
AB  - Coregulation of lymphoid-specific gene sets is achieved by a series of epigenetic
      mechanisms. Association with higher-order chromosomal structures (nuclear
      subcompartments repressing or favouring gene expression) and locus control
      regions affects recombination and transcription of clonotypic antigen receptors
      and expression of a series of other lymphoid-specific genes. Locus control
      regions can regulate DNA methylation patterns in their vicinity. They may induce
      tissue- and site-specific DNA demethylation and affect, thereby, accessibility to
      recombination-activating proteins, transcription factors, and enzymes involved in
      histone modifications. Both DNA methylation and the Polycomb group of proteins
      (PcG) function as alternative systems of epigenetic memory in lymphoid cells.
      Complexes of PcG proteins mark their target genes by covalent histone tail
      modifications and influence lymphoid development and rearrangement of IgH genes.
      Ectopic expression of protein noncoding microRNAs may affect the generation of B
      lineage cells, too, by guiding effector complexes to sites of heterochromatin
      assembly. Coregulation of lymphoid and viral promoters is also possible. EBNA 2,
      a nuclear protein encoded by episomal Epstein-Barr virus genomes, binds to the
      cellular protein CBF1 (C promoter binding factor 1) and operates, thereby, a
      regulatory network to activate latent viral promoters and cellular promoters
      associated with CBF1 binding sites.

PMID- 15959557
TI  - Causes and consequences of DNA hypomethylation in human cancer.
AB  - While specific genes are hypermethylated in the genome of cancer cells, overall
      methylcytosine content is often decreased as a consequence of hypomethylation
      affecting many repetitive sequences. Hypomethylation is also observed at a number
      of single-copy genes. While global hypomethylation is highly prevalent across all
      cancer types, it often displays considerable specificity with regard to tumor
      type, tumor stage, and sequences affected. Following an overview of
      hypomethylation alterations in various cancers, this review focuses on 3
      hypotheses. First, hypomethylation at a single-copy gene may occur as a 2-step
      process, in which selection for gene function follows upon random hypo
      methylation. In this fashion, hypomethylation facilitates the adaptation of
      cancer cells to the ever-changing tumor tissue microenvironment, particularly
      during metastasis. Second, the development of global hypomethylation is
      intimately linked to chromatin restructuring and nuclear disorganization in
      cancer cells, reflected in a large number of changes in histone-modifying enzymes
      and other chromatin regulators. Third, DNA hypomethylation may occur at least
      partly as a consequence of cell cycle deregulation disturbing the coordination
      between DNA replication and activity of DNA methyltransferases. Finally, because
      of their relation to tumor progression and metastasis, DNA hypomethylation
      markers may be particularly useful to classify cancer and predict their clinical
      course.

PMID- 15959558
TI  - Epigenome programming by Polycomb and Trithorax proteins.
AB  - Polycomb group (PcG) and Trithorax group (TrxG) proteins work, respectively, to
      maintain repressed or active transcription states of developmentally regulated
      genes through cell division. Data accumulated in the recent years have increased
      our understanding of the mechanisms by which PcG and TrxG proteins regulate gene
      expression. The discovery that histone methylation can serve as a specific mark
      for PcG and TrxG complexes has provided new insight into the mechanistic function
      of this cell-memory system.

PMID- 15959559
TI  - Many players, one goal: how chromatin states are inherited during cell division.
AB  - Replication of genomic material is a process that requires not only high fidelity
      in the duplication of DNA sequences but also inheritance of the chromatin states.
      In the last few years enormous effort has been put into elucidating the
      mechanisms involved in the correct propagation of chromatin states. From all
      these studies it emerges that an epigenetic network is at the base of this
      process. A coordinated interplay between histone modifications and histone
      variants, DNA methylation, RNA components, ATP-dependent chromatin remodeling,
      and histone-specific assembly factors regulates establishment of the replication
      timing program, initiation of replication, and propagation of chromatin domains.
      The aim of this review is to examine, in light of recent findings, how so many
      players can be coordinated with each other to achieve the same goal, a correct
      inheritance of the chromatin state.

PMID- 15959560
TI  - Role of histone acetylation in the control of gene expression.
AB  - Histone proteins play structural and functional roles in all nuclear processes.
      They undergo different types of covalent modifications, defined in their ensemble
      as epigenetic because changes in DNA sequences are not involved. Histone
      acetylation emerges as a central switch that allows interconversion between
      permissive and repressive chromatin domains in terms of transcriptional
      competence. The mechanisms underlying the histone acetylation-dependent control
      of gene expression include a direct effect on the stability of nucleosomal arrays
      and the creation of docking sites for the binding of regulatory proteins. Histone
      acetyltransferases and deacetylases are, respectively, the enzymes devoted to the
      addition and removal of acetyl groups from lysine residues on the histone N
      terminal tails. The enzymes exert fundamental roles in developmental processes
      and their deregulation has been linked to the progression of diverse human
      disorders, including cancer.

PMID- 15959561
TI  - The role of poly(ADP-ribose) in the DNA damage signaling network.
AB  - DNA damage signaling is crucial for the maintenance of genome integrity. In
      higher eukaryotes a NAD+-dependent signal transduction mechanism has evolved to
      protect cells against the genome destabilizing effects of DNA strand breaks. The
      mechanism involves 2 nuclear enzymes that sense DNA strand breaks, poly(ADP
      ribose) polymerase-1 and -2 (PARP-1 and PARP-2). When activated by DNA breaks,
      these PARPs use NAD+ to catalyze their automodification with negatively charged,
      long and branched ADP-ribose polymers. Through recruitment of specific proteins
      at the site of damage and regulation of their activities, these polymers may
      either directly participate in the repair process or coordinate repair through
      chromatin unfolding, cell cycle progression, and cell survival-cell death
      pathways. A number of proteins, including histones, DNA topoisomerases, DNA
      methyltransferase-1 as well as DNA damage repair and checkpoint proteins (p23,
      p21, DNA-PK, NF-kB, XRCC1, and others) can be targeted in this manner; the
      interaction involves a specific poly(ADP-ribose)-binding sequence motif of 20-26
      amino acids in the target domains.

PMID- 15959562
TI  - DNA break repair: refined rules of an already complicated game.
AB  - Of the many types of DNA-damage repair, this review concentrates on the aspects
      of DNA single- and double-strand break repair. Originally considered to represent
      separate routes based on distinct enzymatic machineries, it has recently been
      shown that these pathways converge and are interlinked at a number of points.
      Poly(ADP-ribose) polymerase-1 (PARP-1) is a central player in this complicated
      game. We present new data and our view on the mechanisms by which PARP-1 is
      guided to its respective interaction partners to coordinate or participate in
      repair or apoptosis.

PMID- 15959563
TI  - Methyl-CpG-binding proteins in cancer: blaming the DNA methylation messenger.
AB  - In recent years, epigenetic alterations have come to prominence in cancer
      research. In particular, hypermethylation of CpG islands located in the promoter
      regions of tumor-suppressor genes is now firmly established as an important
      mechanism for gene inactivation in cancer. One of the most remarkable
      achievements in the field has been the identification of the methyl-CpG-binding
      domain family of proteins, which provide mechanistic links between specific
      patterns of DNA methylation and histone modifications. Although many of the
      current data indicate that methyl-CpG-binding proteins play a key role in
      maintaining a transcriptionally inactive state of methylated genes, MBD4 is also
      known to be involved in excision repair of T:G mismatches. The latter is a member
      of this family of proteins and appears to play a role in reducing mutations at 5
      methylcytosine. This review examines the contribution of methyl-CpG-binding
      proteins in the epigenetic pathway of cancer.

PMID- 15959564
TI  - Caught in conspiracy: cooperation between DNA methylation and histone H3K9
      methylation in the establishment and maintenance of heterochromatin.
AB  - Heritable patterns of gene expression and gene silencing are determined by
      chromatin states that either permit or restrict transcription. Restrictive
      heterochromatin in most eukaryotes is characterized by high levels of DNA
      methylation and histone H3 methylation at lysine 9. The functional relationship
      between these two modifications is the focus of intensive investigation in
      various organisms from fungi to mammals. Complex interactions have been
      discovered among various components of DNA methylation and histone methylation
      pathways, proteins involved in the formation of higher-order chromatin structure,
      chromatin remodelling activities, and RNA interference. This review discusses
      some aspects of this crosstalk and the cooperation between DNA methylation and
      histone H3K9 methylation in the establishment and maintenance of heterochromatin.

PMID- 15959565
TI  - Chromatin architecture and functions: the role(s) of poly(ADP-RIBOSE) polymerase
      and poly(ADPribosyl)ation of nuclear proteins.
AB  - Epigenetic states that allow chromatin fidelity inheritance can be mediated by
      several factors. One of them, histone variants and their modifications (including
      acetylation, methylation, phosphorylation, poly(ADP-ribosyl)ation, and
      ubiquitylation) create distinct patterns of signals read by other proteins, and
      are strictly related to chromatin remodelling, which is necessary for the
      specific expression of a gene, and for DNA repair, recombination, and
      replication. In the framework of chromatin-controlling factors, the poly(ADP
      ribosyl)ation of nuclear proteins, catalysed by poly(ADP-ribose)polymerases
      (PARPs), has been implicated in the regulation of both physiological and
      pathological events (gene expression/amplification, cellular
      division/differentiation, DNA replication, malignant transformation, and
      apoptotic cell death). The involvement of PARPs in this scenario has raised
      doubts about the epigenetic value of poly(ADP-ribosyl)ation, because it is
      generally activated after DNA damage. However, one emerging view suggests that
      both the product of this reaction, poly(ADP-ribose), and PARPs, particularly PARP
      1, play a fundamental role in recruiting protein targets to specific sites and
      (or) in interacting physically with structural and regulatory factors, through
      highly reproducible and inheritable mechanisms, often independent of DNA breaks.
      The interplay of PARPs with protein factors, and the combinatorial effect of
      poly(ADPribosyl)ation with other post-translational modifications has shed new
      light on the potential and versatility of this dynamic reaction.

PMID- 15959566
TI  - C-H...O and other weak hydrogen bonds. From crystal engineering to virtual
      screening.
AB  - Hydrogen bonds, X-H...A, formed by weak donors (X = C) and acceptors (A = pi
      system) were generally dismissed as being of little consequence before and even
      during the 1970s. This situation changed in the early 1980s, and during the two
      following decades they were implicated as being significant in many small
      molecule crystal structures, and also in solution. Today, knowledge gained about
      these interactions is being used to understand the structure of biomolecules with
      implications for structure based drug design.

PMID- 15959567
TI  - Organometallic based strategies for metal nanocrystal synthesis.
AB  - Organometallic strategies normally employed for the production of semiconductor
      quantum dots have been successfully applied to the synthesis of metal
      nanoparticles. By controlling parameters such as capping agents, reaction
      temperature and precursor chemistry, precise nanostructures can be obtained that
      exhibit highly desirable magnetic, optical and catalytic properties.

PMID- 15959568
TI  - Reversible ferromagnetic-antiferromagnetic transformation upon dehydration
      hydration of the nanoporous coordination framework, [Co3(OH)2(C4O4)2].3H2O.
AB  - Reversible crystal-to-crystal transformation accompanied by change from
      ferromagnetic to antiferromagnetic ground states at 8 K upon dehydration
      rehydration of the nanoporous coordination framework [CoII3(OH)2(C4O4)2].3H2O.

PMID- 15959569
TI  - Adding a third dimension to operando spectroscopy: a combined UV-Vis, Raman and
      XAFS setup to study heterogeneous catalysts under working conditions.
AB  - The potential of combined operando UV-Vis/Raman/XAFS has been explored by
      studying the active site and deactivation mechanism of silica- and alumina
      supported molybdenum oxide catalysts under propane dehydrogenation conditions.

PMID- 15959570
TI  - Unusual optical properties of porphyrin fractal J-aggregates.
AB  - A simple mix and shake procedure in aqueous solution from water-soluble
      tetrakis(4-sulfonatophenyl)porphyrin and spermine leads to fractal non-covalent
      supramolecular systems which exhibit unusual large enhancement of resonant light
      scattering, behaving as metal particles.

PMID- 15959571
TI  - Design of photocleavable lipids and their application in liposomal "uncorking".
AB  - The design of o-nitrobenzyl containing photocleavable lipid-amino acid
      conjugates, and their application in liposomal uncorking are described.

PMID- 15959572
TI  - Helical water chains in aquapores of organic hexahost: remarkable halogen
      substitution effect on the handedness of water helix.
AB  - Water helices surrounding the nano-channels of trichlorophloroglucinol and
      tribromophloroglucinol have different handedness, PMPMPM and PPPMMM (P = right
      handed, M = left-handed), depending on halogenhalogen interactions between the
      host molecules.

PMID- 15959573
TI  - Atomistic simulation of charged iron oxyhydroxide surfaces in contact with
      aqueous solution.
AB  - Molecular dynamics simulations of aqueous solution/goethite interfaces show that
      the classical models of the electrical double layer do not accurately describe
      the distribution of ions near the surface (such a distribution is present even
      when the surface is neutral) and that the explicit treatment of solvent molecules
      is essential to capture the effects of the surface on the liquid phase.

PMID- 15959574
TI  - Titanium-mediated [4 + 1] assembly of 1,3-dienes and nitriles: formation of 3
      cyclopentenyl amines and cyclopentenones.
AB  - In the presence of Ti(OiPr)4 and iPrMgCl, dienes couple with nitriles to afford
      the title products in good yields.

PMID- 15959575
TI  - Ionic liquids promote selective responses towards the highly hydrophilic anion
      sulfate in PVC membrane ion-selective electrodes.
AB  - A remarkable enhanced response towards the hydrophilic anion sulfate using
      plasticized PVC membranes containing the ionic liquid 1-butyl-3-methylimidazolium
      hexafluorophosphate and a polyazacycloalkane derivative as ionophore has been
      found.

PMID- 15959576
TI  - A new titanosilicate umbite membrane for the separation of H2.
AB  - A new microporous titanosilicate umbite membrane has been synthesized on
      commercial porous TiO2 tubular supports. This membrane is able to separate H2/N2
      mixtures (with selectivities as high as 48) even in the presence of water.

PMID- 15959577
TI  - Quantitative estimation of NH3 partial pressure in H2 desorbed from the Li-N-H
      system by Raman spectroscopy.
AB  - The partial pressure of NH3 gas estimated by Raman spectroscopy indicates that
      approximately 0.1% NH3 inevitably contaminates the H2 desorbed from a hydrogen
      storage material composed of LiH and LiNH2 at any temperature up to 400 degrees C
      in a closed system.

PMID- 15959578
TI  - Facile and potent synthesis of carbon bridged fullerene dimers (HC60-CR2-C60H
      type).
AB  - Novel carbon bridged fullerene dimers (HC60-CR2-C60H type) are obtained in high
      yield by the reaction of aminomethylenebis(phosphonate) anions with
      [60]fullerene.

PMID- 15959579
TI  - Ethyl 2-acetamido-4,6-di-O-benzyl-2,3-N,O-carbonyl-2-deoxy-1-thio-beta-D
      glycopyranoside as a versatile GlcNAc donor.
AB  - The title donor, ethyl 2-acetamido-4,6-di-O-benzyl-2,3-N,O-carbonyl-2-deoxy-1
      thio-beta-D-glycopyranoside, is shown to be an excellent glycosyl donor giving
      immediate and efficient access to variant GlcNAc-containing oligosaccharides.

PMID- 15959580
TI  - Siletanylmethyllithium: an ambiphilic organosilane.
AB  - The adjacent centres of electrophilicity and nucleophilicity lead to interesting
      chemical reactivity in the title reagent.

PMID- 15959581
TI  - A modular design of ruthenium catalysts with diamine and BINOL-derived
      phosphinite ligands that are enantiomerically-matched for the effective
      asymmetric transfer hydrogenation of simple ketones.
AB  - A method is reported for making a potentially very wide series of ruthenium
      hydrido chloro complexes with diamine and readily-prepared diphosphinite ligand
      modules as precatalysts for the asymmetric transfer hydrogenation of simple
      ketones to give chiral alcohols in good yield and enantioselectivity.

PMID- 15959582
TI  - Theoretical studies on di- and tetra-nuclear Ni pivalate complexes.
AB  - A combination of DFT calculations and magnetic studies allow structural features
      of di- and tetra-nuclear nickel pivalate cage complexes to be deduced.

PMID- 15959583
TI  - Unprecedented use of silver(I) N-heterocyclic carbene complexes for the catalytic
      preparation of 1,2-bis(boronate) esters.
AB  - Catalytic diboration of internal and terminal alkenes with Ag(I) N-heterocyclic
      carbene complexes leads to 1,2-bis(boronate) esters as single intermediates, that
      can be oxidised towards the corresponding diols.

PMID- 15959584
TI  - Ionic diamine rhodium(I) complexes--highly active catalysts for the
      hydroformylation of olefins.
AB  - Rhodium(I) complexes composed of an anionic rhodium centre containing chloride
      ligands, and a cationic rhodium centre coordinated by a diamine ligand, were
      synthesized and characterized. These complexes are able to catalyze the
      hydroformylation reaction under mild reaction conditions in excellent activity
      and regioselectivity, and in the absence of a phosphorus ligand.

PMID- 15959585
TI  - Lewis acid-catalyzed stereospecific ring expansion of aziridine-2-carboxylates to
      imidazolidin-2-ones.
AB  - Lewis acid-catalyzed ring expansion reaction of chiral aziridine-2-carboxylate
      proceeds regio- and stereospecifically to yield enantiomerically pure 4
      functionalized imidazolidin-2-ones in high yields.

PMID- 15959586
TI  - pH-Dependent reversible transformation of TPPS4 anchored on mesoporous TiO2 film
      between monomers and J-aggregates.
AB  - Protonated TPPS4 monomer and its J-aggregate were formed simultaneously from
      TPPS4 adsorbed through its sulfonic acid groups on TiO2 porous film by decreasing
      the pH of the surrounding water and this behavior on TiO2 film can be reversibly
      repeated depending on pH, indicating a flexible and stable arrangement of TPPS4
      through chemical bonds between the sulfonic acid groups and the TiO2 surface.

PMID- 15959587
TI  - Dynamic covalent chemistry on self-templating PNA oligomers: formation of a
      bimolecular PNA quadruplex.
AB  - The tetramolecular PNA quadruplex motif has been probed using a dynamic covalent
      chemistry (DCC) approach to create and characterize a bimolecular PNA quadruplex.

PMID- 15959588
TI  - Bimetallic catalytic synthesis of annelated benzazepines.
AB  - A novel short synthetic route to annelated benzazepines, using additive enhanced
      palladium-indium catalytic 3-component cascade methodology is described.

PMID- 15959589
TI  - Reversible electrochemical monitoring of surface confined reactions at liquid
      liquid interfaces by modulation of ion transfer fluxes.
AB  - The adsorption of the neutral surfactant Brij35 at a liquid-liquid interface is
      reversibly monitored via its disturbance of an electrochemically imposed ion flux
      across the interface, forming a promising experimental tool for the detection of
      surface confined reactions at such liquids and polymers.

PMID- 15959590
TI  - A convergent approach to gamma-carbonyl vinyl boronates.
AB  - Gamma-carbonyl vinyl boronates can be prepared by a visible light induced radical
      chain addition of an S-acyl dithiocarbonate (xanthate) to the pinacol ester of
      vinyl boronic acid, followed by treatment with base.

PMID- 15959591
TI  - Condensed metallaborane clusters: synthesis and structure of Fe2(CO)6(eta5
      C5Me5RuCO)(eta5-C5Me5Ru)B6H10.
AB  - Mild pyrolysis of (eta5-C5Me5Ru)2B6H12 with Fe2(CO)9 yields the 12 skeletal
      electron pair (sep) Fe2(CO)6(eta5-C5Me5RuCO)(eta5-C5Me5Ru)B6H10 cluster; the
      title compound represents a novel class of hybrid multiple cluster in which a
      Fe2B2 tetrahedron has been fused to a ruthenaborane substrate.

PMID- 15959592
TI  - Dynamic kinetic resolution of N-Boc-2-lithiopyrrolidine.
AB  - Asymmetric substitution of the organolithium derived either from N-Boc-2
      tributylstannylpyrrolidine by tin-lithium exchange or from N-Boc-pyrrolidine by
      deprotonation occurs in the presence of a commercially available chiral diamine
      ligand with high levels of enantioselectivity by a dynamic kinetic resolution
      pathway.

PMID- 15959593
TI  - Binuclear Cu2+ complex mediated discrimination between L-glutamate and L
      aspartate in water.
AB  - L-glutamate and L-aspartate selectivity is achieved by the action of two Cu2+
      metal ions rightly disposed in a cyclophane-type macrocyclic framework;
      electrochemical sensing of glutamate has been achieved by adsorption of the
      copper complexes on graphite electrodes.

PMID- 15959594
TI  - Detection of 1,2-hydride shifts in the formation of euph-7-ene by the squalene
      tetrahymanol cyclase of Tetrahymena pyriformis.
AB  - Incubation of samples of 2,3-dihydrosqualene, specifically labeled with deuterium
      at either carbon position 7 or 11, with an enzyme extract from Tetrahymena
      pyriformis, containing a squalene-tetrahymanol cyclase, provided specimens of
      euph-7-enes displaying deuterium patterns consistent with the biosynthetic
      operation of two consecutive 1,2-hydride shifts.

PMID- 15959595
TI  - 1-Dimensional structures of poly(3,4-ethylenedioxythiophene)(PEDOT): a chemical
      route to tubes, rods, thimbles, and belts.
AB  - The chemical synthesis of 1-dimensional (1-D) PEDOT nanostructures in the form of
      tubes, rods, thimbles, and belts has been successfully accomplished through the
      use of a "hard template".

PMID- 15959596
TI  - Macro- and micropulmonary hemodynamic changes to nitric oxide blockade in
      monocrotaline-induced pulmonary hypertension in rats--an in vivo approach.
AB  - BACKGROUND AND PURPOSE: Data on the role of nitric oxide (NO) in monocrotaline
      (MC)-induced pulmonary hypertension of rats have all been derived from in vitro
      measurements. In vivo pulmonary hemodynamics and microvascular responses to NO
      blockade in MC-treated rats have not been reported. The current study evaluated
      the role of NO in live MC-treated rats. METHODS: Male Sprague-Dawley rats (n =
      29) were divided into saline control and MC-treated groups. Three to 4 weeks
      after either saline or MC injection, pulmonary hemodynamics were measured using
      pulmonary arterial catheter and thermodilution techniques. Pulmonary
      microvascular diameter changes were assessed using an intravital microscope.
      RESULTS: Three to 4 weeks after subcutaneous injection of MC (50 mg/kg), MC
      treated rats showed elevated pulmonary arterial pressure compared to control rats
      (23.6 +/- 2.9 mm Hg vs 14.5 +/- 0.8 mm Hg). N(omega)-nitro-L-arginine methyl
      ester (L-NAME, 20 mg/kg, intravenously), an NO synthase inhibitor, produced
      significant increases in pulmonary arterial pressure and total pulmonary vascular
      resistance compared to control rats (12.3 +/- 2.5 mm Hg vs 1.0 +/- 0.9 mm Hg;
      0.21 +/- 0.04 mm Hg/mL/min vs 0.05 +/- 0.02 mm Hg/mL/min, p < 0.05). Intravital
      microscopic observation of the subpleural vessels showed significant
      vasoconstriction in medium-sized (> 40 microm) pulmonary arterioles of MC-treated
      rats following L-NAME administration (58.4 +/- 3.6 microm vs 47.1 +/- 3.4 microm,
      p < 0.05) while no significant diameter changes were found in either the small
      sized (< 40 microm) pulmonary arterioles or pulmonary venules. Diameters of
      pulmonary arterioles and venules in control rats were not affected by L-NAME
      administration. CONCLUSION: Pulmonary arterial pressure and pulmonary vascular
      resistance increased after NO blockade in live MC-treated rats. The site of
      vasoconstriction after NO blockade included medium-sized pulmonary arterioles but
      not small-sized pulmonary arterioles. This study has provided both macro- and
      microhemodynamic evidence of a modulatory role of NO in live MC-treated rats.

PMID- 15959597
TI  - Survey of psychiatric disorders in a Taiwanese village population six months
      after a major earthquake.
AB  - BACKGROUND AND PURPOSE: The catastrophic Chi-Chi earthquake of September 21, 1999
      in Taiwan provided a unique opportunity to study the disaster's psychiatric
      impact on survivors. This study assessed the development of psychiatric disorders
      among residents in a Taiwanese village near the epicenter of the earthquake
      within 6 months of the disaster. METHODS: A total of 442 of the 602 actual living
      residents of Tong-Chi village who were over 16 years of age and were present in
      the community at the time of the earthquake were included in this population
      survey. Subjects were interviewed by psychiatrists using the Mini-International
      Neuropsychiatric Interview and questionnaires to collect demographic information
      and risk factors for psychiatric disorders 4 to 6 months after the earthquake.
      RESULTS: The prevalence rates were 9.5% for current major depression, 2.8% for
      past major depressive episode, and 7.9% for post-traumatic stress disorder
      (PTSD). Females had significantly higher rates of most psychiatric disorders.
      After controlling for covariates, the significant risk factors for PTSD were
      female gender and having sought medical service after the earthquake. Significant
      risk factors for major depressive episode were divorced/widowed status, education
      level equal to or below primary school, and prominent house damage. CONCLUSION:
      This population survey of earthquake disaster survivors found an increased
      prevalence of psychiatric disorders after exposure to a catastrophic earthquake.
      These results highlight the need for prompt therapeutic attention to residents of
      earthquake disaster areas after the event.

PMID- 15959598
TI  - Impact of nosocomial infections on medical costs, hospital stay, and outcome in
      hospitalized patients.
AB  - BACKGROUND AND PURPOSE: Nosocomial infections have been shown to be associated
      with increased attributable mortality, length of hospital stay, and health care
      costs in studies mainly conducted in western populations. However, the health
      care system in Taiwan differs from the typical situation in western countries,
      with longer hospitalization times and lower daily costs. The purpose of this
      study was to understand the economic and clinical impacts of nosocomial
      infections in Taiwan. METHODS: Between June 1, 2001 and December 31, 2001, every
      hospitalized patient (age >/= 16 years) with nosocomial infections (case group)
      and matched control patients without nosocomial infections of the same age,
      gender, underlying medical illness, clinical diagnosis at admission and disease
      severity (control group) were recruited. Demographic characteristics, length of
      hospitalization, costs and final outcomes of both groups were collected for
      analysis. RESULTS: A total of 482 patient-pairs with median age of 68 years were
      studied. The median length of hospital stay was 40 days for the case group and 22
      days for the control group (p < 0.0001). The median hospital cost for the case
      group was 363,425 New Taiwan Dollars (NTD) and 165,965 NTD for the control group
      (p < 0.0001). The median additional hospital stay for patients with nosocomial
      infection was 15 days, which amounted to 127,354 NTD. The extra hospital costs
      were not only associated with accommodation but also fees for materials, and
      costs relating to pharmacy, laboratory tests and diet. Patients with nosocomial
      infections were more likely to have shock, organ failure and death (all p <
      0.0001). Additional hospital stay and costs were not related to various infection
      sites and bacterial pathogens causing nosocomial infections; however, medical
      costs attributable to nosocomial fungal infection were higher than that of
      bacterial infections. CONCLUSIONS: Nosocomial infections have a significant
      impact on the length of hospital stay and medical care cost. Extra costs of
      nosocomial infections resulted not only from prolongation of hospital stay, but
      also other medical costs. Infection control for preventing nosocomial infections
      may play an important role in reducing medical costs, hospital stay, and
      mortality in hospitalized patients.

PMID- 15959599
TI  - Low frequency of target organ damage in Taiwanese with white coat hypertension.
AB  - BACKGROUND AND PURPOSE: The clinical importance of white coat hypertension (WCH)
      remains to be clarified. This study investigated the target organ damage in
      Taiwanese with WCH. METHODS: A total of 188 consecutive Taiwanese (88 men and 100
      women), aged 26 to 75 years who had an abnormal office casual blood pressure
      (systolic blood pressure >/= 140 mm Hg or diastolic blood pressure >/= 90 mm Hg
      or both) and a normal ambulatory blood pressure (ABP) average (systolic ABP
      average < 140 mm Hg and diastolic ABP average < 90 mm Hg) at the outpatient
      clinic or from a mass survey were enrolled. Office casual blood pressure
      measurements were obtained by standard sphygmomanometric methods. Twenty-four
      hour blood pressures were recorded by a commercial ambulatory pressure recorder
      (Del Mar Avionics, Model 1990 Pressurometer IV System). Hypertension-related
      target organ complications were assessed by electrocardiogram, chest X-ray,
      urinalysis and eye fundus examinations. RESULTS: Target organ damage was found in
      6.4% of subjects with WCH. Roentgenographic left ventricular hypertrophy (LVH)
      was found in 1.1% of subjects and electrocardiographic LVH in 2.7%. Proteinuria
      was found in 1.6% of subjects and retinopathy in 1.1%. The frequencies of various
      target organ damage were not significantly associated with age, gender and the
      definition of normal ABP average as 135/85 mm Hg or 140/90 mm Hg. CONCLUSIONS:
      WCH represents a low-risk stratum for target organ damage in Taiwanese. These
      subjects should be identified and followed up regularly. The factors responsible
      for the low frequency of target organ damage in Taiwanese with WCH need further
      study.

PMID- 15959600
TI  - Neoplastic disorders of hematopoiesis in children with Down's syndrome--a single
      institution experience in Taiwan.
AB  - BACKGROUND AND PURPOSE: Children suffering from Down's syndrome (DS) are
      predisposed to the development of neoplastic disorders of the hematopoietic
      system and tend to display many unique characteristics. This study analyzed the
      clinical characteristics and treatment outcomes of 16 children with DS who
      developed neoplastic disorders. METHODS: All DS patients aged < 18 years of age
      with a diagnosis of leukemia or myelodysplastic syndrome (MDS) from 1990 to 2002
      were included in this retrospective study. The clinical and laboratory
      characteristics of patients, including age at diagnosis, gender, initial
      hemogram, cytogenetic findings, immunophenotype, treatment regimen and outcomes
      were analyzed. RESULTS: Sixteen patients met the inclusion criteria. Among them,
      9 patients (56%) had acute myeloid leukemia (AML), mainly of the megakaryoblastic
      subtype. All 8 AML patients who had analyzable metaphase cells revealed clonal
      chromosomal abnormalities in addition to trisomy 21. Three of these patients
      developed MDS prior to the onset of AML. Of the 5 patients who underwent
      chemotherapy, 3 remained in remission with a survival time of 29, 59, and 109
      months, and the remaining 2 died as a consequence of chemotherapy toxicity. Among
      the 6 patients (38%) who developed transient myeloproliferative disorder, 2 were
      lost to follow-up, 2 died from DS-associated congenital heart abnormalities and 2
      survived without any AML changes. The remaining 1 patient (6%) who developed ALL
      was still in his first remission although this patient suffered profound
      chemotherapy complications during treatment. CONCLUSIONS: This study found that
      AML is the most common hematologic neoplasm in Taiwanese children with DS,
      especially megakaryoblastic leukemia. This finding is comparable to the reported
      results from related studies in different countries. Long-term remission of AML
      in DS patients can be achieved with appropriate treatment.

PMID- 15959601
TI  - Survival analysis for adult glioma in England and Wales.
AB  - BACKGROUND AND PURPOSE: To investigate factors influencing survival for adult
      glioma at the national population level, data from the Cancer Registry in England
      and Wales were analyzed. Glioma was diagnosed in 32,267 patients during 1971-1990
      and follow-up data were available for these patients until 1995. METHODS: Median
      survival and crude survival rates (CSR) for 8 variables (age, gender,
      International Classification of Diseases for Oncology [ICD-O] morphology, World
      Health Organization [WHO] grade, tumor site, deprivation, geographical region,
      and period of diagnosis) were calculated and tested using the Kaplan-Meier method
      and the log-rank test. Relative survival rates (RSR) were calculated using the
      life table of 1981. Cox multivariate regression was performed for estimating
      hazards ratios (HR) and tested using the log likelihood ratio test. RESULTS: The
      median survival and the 1-, 5-, and 10-year CSR for this population were 0.42
      years, 29.1%, 12.0%, and 7.7%, respectively. The 1- and 5-year RSR were 29.6% and
      12.3%, respectively. Survival was influenced by all 8 variables tested (p </=
      0.025). Age at diagnosis was the most influential factor (HR, 1.22/5 years).
      Females had better survival than males (HR, 0.94). Patients with unspecified
      gliomas had the worst survival, while those with ependymoma had the best
      survival. Tumors in the posterior fossa were associated with better survival than
      those in the cerebral hemisphere. Survival was associated with the WHO grade and
      the level of deprivation, and had regional differences. Survival improved by 16%
      between 1971-1975 and 1986-1990. CONCLUSION: Survival in adult glioma is
      influenced by multiple factors, including socioeconomic background. However, age
      at diagnosis and tumor characteristics are the most influential factors.

PMID- 15959602
TI  - Relationship of anatomic classifications to degenerative changes in untreated
      developmental dysplasia of the hip.
AB  - BACKGROUND AND PURPOSE: In untreated developmental dysplasia of the hip (DDH),
      degenerative changes of the femoral heads develop mainly in hips with
      pseudoacetabular formation. But degenerative changes may also occur due to
      friction between the femoral heads and surrounding soft tissues after prolonged
      walking. The purpose of this study was to investigate the relationship between
      anatomic classifications of DDH and clinical manifestations. METHODS: Twenty five
      consecutive patients with untreated DDH who underwent open reduction and
      reconstructive surgery between 1982 and 2001 were included in this retrospective
      analysis. All of the patients were female and had unilateral dislocation. The age
      of the patients ranged from 12 to 28 years (median, 17 years). The relationships
      among preoperative and postoperative radiographs, and between clinical symptoms,
      and gross pathology at surgery were analyzed. RESULTS: Based on the height of
      dislocation and pseudoacetabular formations on plain radiographs, 3 types of
      dislocations were recognized: 1) low dislocation with pseudoacetabular formation
      in 6 hips; 2) high dislocation with definite pseudoacetabular formation in 4
      hips; and 3) high dislocation without definite pseudoacetabular formation in 15
      hips. The incidence of pain, dystrophic radiographic change of the femoral head
      and the presence of degenerative change at the time of surgery were significantly
      greater in hips with high dislocation and pseudoacetabular formation and patients
      with high dislocation without pseudoacetabulum formation (p < 0.05). CONCLUSION:
      Degenerative change of the femoral heads can develop in untreated dislocated hips
      of patients with skeletally mature DDH regardless the height of dislocation and
      pseudoacetabular formation.

PMID- 15959603
TI  - Successful treatment with peginterferon and ribavirin in a patient with acute
      hepatitis C evolving into chronicity.
AB  - Acute hepatitis C has a high frequency of chronic evolution, which may progress
      to cirrhosis and hepatocellular carcinoma. However, only a small proportion of
      acute hepatitis C patients are incidentally identified and then treated.
      Controversial issues regarding treatment of acute hepatitis C include optimal
      time of treatment initiation, best treatment regimen and appropriate duration of
      treatment. We report a symptomatic acute hepatitis C patient in the late acute
      phase evolving into chronicity successfully treated by peginterferon and
      ribavirin combination therapy for 6 months at late acute phase, with sustained
      virologic response for up to 18 months. Our findings indicate that combination
      peginterferon and ribavirin therapy may be as effective in treating acute
      hepatitis C as it is in chronic hepatitis C.

PMID- 15959604
TI  - Successful balloon pulmonary valvuloplasty for congenital valvular pulmonary
      stenosis in an octogenarian.
AB  - While balloon valvuloplasty has been widely used for the treatment of congenital
      valvular pulmonary stenosis (PS) in children and adults, its use in elderly
      patients is less common. An 80-year-old woman with congenital valvular PS
      received valvuloplasty with double-balloon technique. Right ventricle systolic
      pressure and pulmonary valve systolic pressure gradient decreased from 95 to 44
      mm Hg and from 75 to 35 mm Hg, respectively. Follow-up Doppler echocardiography 2
      months later showed further decrease in the transvalvular systolic pressure
      gradient to 29 mm Hg. The patient had symptomatic relief, and no major
      complication was noted. Balloon pulmonary valvuloplasty can be an effective
      treatment for elderly patients with congenital valvular PS.

PMID- 15959605
TI  - Rare presentation of endocrine pancreatic tumor: a case of diffuse glucagonoma
      without metastasis and necrolytic migratory erythema.
AB  - Glucagonoma is a very rare endocrine pancreatic tumor. At diagnosis, most
      glucagonomas are malignant and often metastatic. Suspicion of glucagonoma is
      based on characteristic presentations known as "glucagonoma syndrome".
      Glucagonoma is often found in the pancreatic body and/or tail and is usually
      large enough to be localized by computed tomography. We report a case of diffuse
      glucagonoma necrolytic migratory erythema (NME) in a 45-year-old man with mild
      diabetes mellitus, mild anemia, and weight loss over 1.5 years. Diffused enlarged
      pancreas was noted on abdominal ultrasonography incidentally during a routine
      health check-up. The levels of carcinoembryonic antigen and carbohydrate antigen
      19-9 were within normal limits. No enlarged lymph node or extrapancreatic tumor
      mass was found by several imaging studies. Total pancreatectomy was performed,
      and the pathology revealed glucagon-producing islet cells and intrapancreatic
      vascular emboli of tumor cells. He died due to internal bleeding and sepsis after
      surgery. Presentation of diffuse malignant glucagonoma with tumor emboli but no
      metastasis or NME is unusual.

PMID- 15959607
TI  - Loosening of total hip arthroplasty with a prosthesis employing a skirted femoral
      head.
AB  - In total hip arthroplasty, a modular femoral head with a flange increases the
      head-neck strength and compensates the leg length, but results in a decreased
      head-to-neck diameter ratio. Studies have shown increased chance of impingement
      and incidence of dislocation associated with a skirted femoral head component.
      However, the relation between implant loosening and the skirted neck has not been
      well demonstrated. We report a 41-year-old male patient with aseptic loosening of
      total hip arthroplasty due to osteolysis of both acetabular and femoral
      components 5 years after surgery. The retrieved prostheses demonstrated
      polyethylene wear due to impingement of the skirted head during hip flexion.
      Pathologic examination showed prominent foreign body reaction. Prosthetic
      impingement occurs due to malposition of components and extreme posture. A
      decreased head-to-neck diameter ratio further compromises prosthetic range of
      motion. A skirted femoral head component should be used with caution.

PMID- 15959606
TI  - Dizygotic twins discordant for early-onset Citrobacter koseri and group B
      streptococcal sepsis.
AB  - Early-onset neonatal sepsis is usually a multisystem fulminant illness with
      prominent respiratory symptoms, and typically the infant has acquired the
      organism from the maternal genital tract during the intrapartum period. In this
      article, we report a rare case of dizygotic twins where each individual suffered
      early-onset sepsis caused by a different pathogen. Group B streptococcal (GBS)
      sepsis was diagnosed in twin A 1 day after birth; sepsis and meningitis caused by
      Citrobacter koseri was diagnosed in twin B at the age of the 4 days. The mother
      developed pre-eclampsia and fever and the twins were delivered via cesarean
      section at 35 week's gestation. Twin A received ampicillin treatment for 14 days
      and recovered fully. Twin B was treated with ceftriaxone for 4 weeks and follow
      up brain ultrasound revealed persistent enlargement of the bilateral-lateral
      ventricles. When empiric antibiotic is considered for the symptomatic twin of a
      sibling with early-onset GBS infection, samples of blood and cerebrospinal fluid
      (CSF) should be obtained for culture study before treatment. Adjustment of
      antibiotic treatment based on the results of cultures and CSF Gram stain and
      antibiotic susceptibility test is essential.

PMID- 15959608
TI  - Vasodilator agents inhibit opossum kidney proximal tubular cell growth.
AB  - Renal tubule cell hyperplasia and hypertrophy have been regarded as antecedents
      of tubulointerstitial fibrosis. Dipyridamole and pentoxifylline inhibit rat
      glomerular mesangial cell growth. The purpose of this study was to examine the
      effects of pentoxifylline and other vasodilators on opossum kidney proximal
      tubular (OKP) cell growth. A modified 3-(4,5-dimethylthiazil-2-yl)-2,5
      diphenyltetrazolium bromide assay was used to evaluate cell proliferation in OKP
      cells. Pentoxifylline caused a dose-dependent inhibition of serum-stimulated
      proliferation of OKP cells: inhibition was 17%, 25%, and 37% at 0.03 mg/mL, 0.1
      mg/mL, and 0.3 mg/mL, respectively. Dipyridamole 1.7 mg/L and 6 mg/L resulted in
      34% and 46% inhibition, respectively. Verapamil 10(-6) M, 10(-5) M, and 10(-4) M
      resulted in 34%, 46%, and 67% inhibition, respectively. These inhibitory effects
      may contribute to renal protection or retardation of renal disease progression.

PMID- 15959609
TI  - [External genital injuries. Diagnostics and treatment].
AB  - This article reviews the current status of information on external male genital
      injuries, focusing on the causes as well as diagnostic and therapeutic management
      of this uncommon entity. Because of the high risk of infection and the major
      importance of preserving fertility, male genital injuries represent a serious
      urological disorder that demands immediate urological treatment. The diagnostic
      procedure classically consists of taking a history and inspecting the wound,
      which provides enough diagnostic information for the correct choice of
      conservative or surgical treatment. In most cases open injuries of the genitalia
      require surgical exploration to determine the extent of possible scrotal,
      testicular, epididymal, cavernous, or urethral damage, to debride nonviable
      superficial or deep tissue, to drain existing hematomas, or to control active
      bleeding. Furthermore, the correct therapeutic approach is crucial for preserving
      fertility and penile erection. In cases where bilateral ablation is necessary,
      measures to preserve sperm, e.g., testicular or microsurgical sperm extraction,
      or squeezing the ductus during orchidectomy must be considered.

PMID- 15959610
TI  - [Bladder injury. Diagnostics and treatment].
AB  - Bladder injuries are caused by high-energy blunt trauma that disrupt the bony
      pelvis, a direct blow to a distended bladder, penetrating injuries, or various
      iatrogenic causes. When diagnosis is prompt and treatment adequate respecting the
      other possible injuries, complications from bladder injuries are rare. Problems
      may occur when the diagnosis is delayed. A systematic approach following the
      prescribed guidelines will help to successfully manage these cases.

PMID- 15959611
TI  - [Voluntary micturition after intradural nerve anastomosis].
AB  - INTRODUCTION: One of the major challenges in neuro-urology is the restoration of
      voluntary voiding in a patient after spinal cord injury (SCI). ANIMAL
      EXPERIMENTS: The earliest reports on reconstruction of urinary bladder function
      by bridging nerve roots from above the SCI to the below this level were published
      by Carlsson and Sundin 1968. In another approach, a possible reflex pathway below
      the SCI to reinitiate voluntary voiding was investigated. The result was a
      modified somatic reflex arc rostral to the sacral spinal micturition center.
      FUTURE RESEARCH: Medical reports in numerous publications are still very
      enthusiastic about the possibility of cell or gene therapy. Such results report
      the successful bridging of small nerve gaps. The latest approach is the
      intravenous application of stem cells to aid the recovery of the SCI. CLINICAL
      APPROACH: The first reports on attempts to reconstruct the nervous pathways to
      the bladder in patients were published 1967. In two cases, a nerve anastomosis
      from Th(12) (the lowest intact segment) to S(2+3), bilaterally to the SCI,
      allowed spontaneous micturition after 8-12 months with reported sensitivity at
      the base of the penis. With a modification in surgical technique, another group
      reported a success rate of 100% using the anastomosis of intercostal nerves
      Th(11+12) to sacral roots S(2+3) to establish a reflex voiding and, in 72% of
      patients, reappearance of the bulbocavernous and cremaster reflexes. Xiao et al.
      published, with a 3 year follow-up, the creation of a micturition reflex through
      anastomosing the ventral roots of L(5) to S(2/3) in complete SCI patients with a
      67% success rate a year after surgery. CONCLUSION: There is still a great deal of
      work required before cell therapy becomes a therapeutic option. Today, the
      published data strongly suggest that it is possible to treat first line urinary
      bladder dysfunctions in SCI or spina bifida patients. Before one of these
      techniques becomes widely used, it should be proven effective in specialized
      institutions, such as the Department of Urology in collaboration with the
      Department of Neurosurgery at the University of Tuebingen, Germany.

PMID- 15959612
TI  - The effects of bethanechol and cisapride on urodynamic parameters in patients
      undergoing radical hysterectomy for cervical cancer. A randomized, double-blind,
      placebo-controlled study.
AB  - To evaluate the effects of bethanechol and cisapride on urodynamic parameters in
      patients undergoing radical hysterectomy for cervical cancer. In this double
      blind, placebo-controlled study, 79 patients with cervical cancer were randomized
      to receive bethanechol (30 mg/day), cisapride (30 mg/day), bethanechol combined
      with cisapride (same doses) and placebo. Urodynamic study was performed,
      including flowmetry, cystometry, pressure-flow study and urethral pressure
      profile before radical hysterectomy. Medication was administered postoperatively
      during 30 days. At the end of this period, urodynamic evaluation was repeated.
      There was an increase in both the maximum cystometric capacity and bladder
      capacity at first desire to void in the placebo group compared to the other
      groups. The rate of detrusor instability was higher in the group that used
      bethanechol combined with cisapride. Detrusor pressure at maximum flow was
      significantly higher when cisapride was used. There was a significant increase in
      postvoid residual volume in the placebo group. In patients undergoing radical
      hysterectomy, bethanechol and cisapride determined lower cystometric capacity and
      decreased bladder capacity at first desire to void, a higher maximum flow rate
      and higher detrusor pressure at maximum flow, with lower postvoid residual
      volumes. The early use of bethanechol and cisapride after radical hysterectomies
      positively modified urodynamic parameters, determining a more efficient detrusor
      function.

PMID- 15959613
TI  - High bone mineral density among perimenopausal women.
AB  - Studies regarding high bone mineral density (HBMD) are few. In the population
      based Kuopio Osteoporosis Risk Factor and Prevention Study, BMDs of women were
      measured from 1990-1991 and 1995-1997. The mean age of the 1,873 women studied
      was 53.5 years at baseline (range 48.0-59.6). In all, 248 women were excluded
      because of BMD measurement errors or artifacts: 41 from the HBMD group (20.6%)
      and 207 (12.4%) from the control group. The final study group consisted of 1,551
      women, 168 in the HBMD group (baseline lumbar BMD >1.23 g/cm2; femoral BMD >1.01
      g/cm2, and 5-year follow-up lumbar BMD >1.21 g/cm2; femoral BMD >0.98 g/cm2,
      respectively) and 1,383 in the control group. The predictors for HBMD in the
      multivariate regression analysis were as follows: hormone therapy (HT) during the
      follow-up from 0.5 to 2 years and for over 2 years (OR 2.06, CI: 1.11-3.81 and OR
      2.16, CI 1.43-3.26) and being overweight (BMI from 25 kg/m2 to 30 kg/m2, and BMI
      >30 kg/m2) at baseline (OR 2.84, CI: 1.82-4.42; OR 5.94, CI: 3.47-10.16,
      respectively). High physical activity while 11-18 years of age was associated
      with HBMD (OR 1.69, CI: 1.17-2.45). Parity predicted HBMD so that after one to
      two births the OR was 2.66 (CI: 1.03-6.88) and 3.03 (CI: 1.16-7.90) after three
      or more births. Menopause was negatively associated with HBMD (OR 0.57, CI 0.38
      0.85). There were more premenopausal women in the HBMD group (53.9 vs. 34.6%, P
      <0.001). The HBMD group showed fewer fractures. In conclusion, being overweight,
      parity, HT use, premenopause and high physical activity in adolescence seemed to
      be predictors for persistently high BMD in early postmenopausal women. We suggest
      that the fracture risk is low in these women, and thus they are neither primary
      candidates for BMD screening nor for osteoporosis medication.

PMID- 15959614
TI  - A new concept for bisphosphonate therapy: a rationale for the development of
      monthly oral dosing of ibandronate.
AB  - Oral daily and weekly bisphosphonates represent the current mainstay of treatment
      for postmenopausal osteoporosis (PMO). However, the inconvenience of frequent
      dosing is known to negatively affect adherence to therapy in the long term. This
      has prompted the development of convenient oral bisphosphonate regimens that
      feature simple, less frequent dosing schedules. Such regimens require high
      potency agents, which can be given at low effective doses and that also have good
      tolerability. Ibandronate is a potent, nitrogen-containing bisphosphonate with
      proven efficacy when given intermittently to estrogen-depleted beagle dogs, rats
      and cynomolgus monkeys. Clinically, a pivotal prospective study has established
      that oral ibandronate has significant vertebral fracture efficacy in PMO, whether
      given daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every
      3 months; extended between-dose interval>2 months). Both oral regimens were well
      tolerated, which is noteworthy as patients with a history of gastrointestinal
      (GI) disturbance were not specifically excluded. As a result of these findings, a
      large, multinational, randomized, double-blind study (Monthly Oral iBandronate In
      LadiEs: MOBILE) is currently exploring the non-inferiority of once-monthly oral
      ibandronate (100 or 150 mg) to the oral daily ibandronate (2.5 mg) regimen with
      proven anti-fracture efficacy, in terms of lumbar spine bone mineral density
      (BMD) change. As with the trials investigating the weekly administration of other
      bisphosphonates, vertebral fracture efficacy will be inferred if the study
      demonstrates the non-inferiority of once-monthly ibandronate to the proven oral
      daily regimen in terms of spinal BMD change. The availability of this once
      monthly ibandronate regimen is expected to offer benefits in terms of convenience
      (by having to follow dosing recommendations once a month vs. once daily or
      weekly) and potentially tolerability (by reducing the potential for upper GI
      irritation that can result from frequent, repeated exposure). Greater convenience
      and tolerability may enhance the therapy adherence and, hence, improve long-term
      therapeutic outcomes in PMO.

PMID- 15959615
TI  - Factors related to spinal mobility in patients with postmenopausal osteoporosis.
AB  - Quality of life in patients with spinal osteoporosis is impaired by the decline
      of spinal mobility. However, the factors related to the spinal mobility in these
      patients are still unclear. We evaluated the possible factors affecting spinal
      mobility in patients with postmenopausal osteoporosis. A total of 128
      postmenopausal women with osteoporosis aged over 50 years (mean, 70 years) were
      included in this study. The thoracic and lumbar kyphosis angles and range of
      motion (ROM) of the total spine were measured in the upright position and at
      maximum flexion/extension with a computer-assisted device. The paravertebral
      muscle thicknesses (PVMT) of thoracic and lumbar spine in the upright position
      were measured using an ultrasound unit. The number of vertebral fractures was
      evaluated with radiographs of the spine. Isometric back extensor strength (BES)
      was evaluated with a strain-gauge dynamometer. Correlations between these
      variables were then analyzed. Age (r=-0.412), lumbar kyphosis angle (r=-0.284),
      BES (r=0.369), PVMT at the lumbar spine (r=0.227) and the number of vertebral
      fractures (r=-0.260) showed significant correlations with total spinal ROM
      (P<0.05). However, no significant correlations were observed between the total
      spinal ROM and PVMT at the thoracic spine (r=-0.069) or thoracic kyphosis angle
      (r=-0.138). Multiple regression analysis revealed that the BES was the most
      significant contributor to the total spinal ROM. The present study suggests a
      possible association between BES and spinal mobility in patients with
      postmenopausal osteoporosis.

PMID- 15959616
TI  - Bone status of Indian women from a low-income group and its relationship to the
      nutritional status.
AB  - Indian women from low-income groups consume diets that have inadequate calcium
      coupled with too few calories, proteins and micronutrients. Hospital-based data
      suggest that these women have osteoporotic hip fractures at a much earlier age
      than Western women. Studies reporting bone parameters of the Indian population
      involving large sample sizes are not available. This study was therefore carried
      out with 289 women in the 30-60-year age group to estimate the prevalence of
      osteoporosis and measure the bone parameters by dual energy X-ray absorptiometry
      (DXA). Their mean (+/- SD) age was 41.0+/-8.60 years. Their mean (+/- SD) height,
      weight and body mass index (BMI) were 149.1+/-5.49 cm, 49.2+/-9.85 kg and 22.1+/
      3.99, respectively. Dietary intake of calcium was estimated to be 270+/-57
      mg/day. The prevalence of osteoporosis at the femoral neck was around 29%. Bone
      mineral density (BMD) and T scores at all the skeletal sites were much lower than
      the values reported from the developed countries and were indicative of a high
      prevalence of osteopenia and osteoporosis. BMD showed a decline after the age of
      35 years in cases of the lumbar spine and femoral neck. This was largely due to a
      decrease of bone mineral content (BMC). The nutritional status of women appears
      to be an important determinant of bone parameters. BMD and BMC at all the
      skeletal sites and whole body increased significantly with increasing body weight
      and BMI of women (P<0.05). However, bone area (BA) did not change with an
      increase in BMI. In the multiple regression analysis, apart from body weight,
      age, menopause and calcium intake were the other important determinants of BMD
      (P<0.05). In addition to these, height was also an important determinant of WB
      BMC. This study highlights the urgent need for measures to improve the
      nutritional status, dietary calcium intake and thus the bone health of this
      population.

PMID- 15959617
TI  - Absorption of the oral bisphosphonate alendronate in osteoporotic patients with
      Crohn's disease.
AB  - The absorption of bisphosphonates from the gut is poor. The question arises
      whether the absorption of alendronate, and thus its bioavailability, is further
      altered by the local inflammatory process in patients with Crohn's disease,
      thereby potentially affecting clinical outcome when used in the treatment of
      osteoporosis. To address this question, urinary excretion of alendronate was
      evaluated 3 months and 6 months after start of treatment with oral alendronate at
      a dose of 10 mg/day in 19 osteoporotic patients with stable Crohn's disease, 12
      of whom had an intestinal resection. Biochemical parameters of bone turnover and
      BMD were also measured at start and at 6 months. Thirteen patients had been
      previously treated with glucocorticoids and five were currently using them. The
      average 24-h urinary excretion of alendronate was 0.5-0.6% of the dose
      administered, a figure comparable to that reported for osteoporotic patients
      without gut pathology. There was a significant decrease from baseline in urine N
      telopeptides of collagen cross-links (NTx)/creatinine (60%) associated with an
      increase in lumbar spine BMD of already 2% after 6 months of treatment. Our data
      suggest that in patients with Crohn's disease, alendronate is adequately absorbed
      from the intestine and retained in the skeleton. This adequacy is confirmed by
      appropriate suppression of bone resorption and increase in lumbar spine BMD.
      These data hold significant implications for the clinical management of patients
      with Crohn's disease and osteoporosis.

PMID- 15959618
TI  - Degenerative anatomic deformities in the foramen transversarium of cadaveric
      cervical vertebrae.

PMID- 15959619
TI  - Establishment of BMD reference curves at different skeletal sites in women, using
      a Cartesian coordinate numeration system.
AB  - The BMD reference curve is the reference value used for diagnosing osteoporosis
      and assessing bone mass changes. Its accuracy would affect the correctness of T
      score and Z-score values and thus the reliability of diagnostic results. In this
      paper, we report the use of a new method, a Cartesian coordinate numeration
      system, to establish BMD reference curves at different skeletal sites in women.
      In a reference population of 3,919 women ranging in age from 5-85 years, we used
      the dual X-ray absorptiometry (DXA) bone densitometer to measure BMD at the
      posteroanterior spine (PA; vertebrae L1-L4), followed by a paired PA/lateral
      spine scan of the vertebral bodies of L2-L4, expressed in g/cm2 and g/cm3, and of
      the hip and forearm. We chose the cubic regression model to best fit BMD curves
      that varied with age at different skeletal sites. We then referred the BMD of the
      fitting curves established by the method of the coordinate numeration system as
      reference curves, compared them to BMD reference curves derived from the fitting
      curve equation or age cross-section, and calculated the deflection degrees of the
      BMD reference curves acquired from the fitting curve equation. At the PA spine,
      lateral spine (expressed in g/cm3), femoral neck, Ward's triangle and radius +
      ulna ultradistal, the reference curves calculated from the equation were
      significantly lower than those confirmed by the method of the coordinate
      numeration system; whereas, at the lateral spine (expressed in g/cm2), total hip,
      and radius + ulna 1/3 sites, the reference curves derived from the equation were
      markedly higher than those acquired from the coordinate numeration system. The
      differences in the two kinds of reference curves calculated by these two
      different methods gradually increased along with the increment in ages of the
      women. At the peak value of the reference curves, the BMD calculated from the
      equation deflected from 2.02% to -10.0% from the BMD acquired from the coordinate
      numeration system at different skeletal sites, and from 21.5% to -121.8% until
      the age of 85 years. The highest positive deflection of 65.2% existed at the
      lateral spine (expressed in g/cm2) and the lowest positive deflection of 21.5% at
      the total hip. The maximum negative deflection of -121.8% was at the radius +
      ulna ultradistal, and the minimum negative deflection of -32.6% at the PA spine.
      The BMD curve acquired from age cross-section was highly positive compared with
      the one derived from the coordinate numeration system (r=0.955-0.985 p=0.000)
      with no significant difference between them. Various analysts used such a method
      to obtain the coefficient of variance (CV) in BMD precision on each curve that
      was from 0.05-0.19%. Our study shows that the Cartesian coordinate numeration
      system is an accurate, precise and reliable method and can serve to reveal the
      serious drawbacks of using the fitting curve equation to calculate BMD. The BMD
      reference curves established by this coordinate numeration system maintained the
      authenticity of the fitting curve, whereas, using the fitting curve equation to
      obtain BMD reference curves at different skeletal sites led to distortion, and
      resulted in false increases or decreases in T-score and Z-score values.

PMID- 15959620
TI  - Camurati-Engelmann disease (progressive diaphyseal dysplasia) in a Moroccan
      family.
AB  - We report on a 46-year-old mother of Moroccan origin, suffering mainly from
      painful, swollen legs, and her 26-year-old son who had experienced intense pain
      in his legs, without fever, for approximately 3 years. They did not have
      dysmorphic features or abnormal gaits. Radiographic studies of the mother
      revealed diaphyseal sclerosis of the tibia and spondylosis of the thoracal and
      lumbar vertebrae. The son had sclerosis of the diaphyses of the metacarpalia of
      the left hand, the femur and the fibula. The other parts of the skeleton were
      normal. Several osteosclerotic/hyperostotic disorders, such as melorheostosis
      (present mostly in sporadic cases and affecting lower extremities) and van
      Buchem's disease (autosomal recessive and commonly affecting the mandible) were
      considered as a diagnosis in the proposita. However, similar symptoms in the son
      of the proposita suggested an autosomal dominant inheritance pattern. This
      brought us to the diagnosis of progressive diaphyseal dysplasia (PDD) or Camurati
      Engelmann disease (CED), an autosomal dominant disorder characterized by limb
      pain, reduced muscle mass, weakness, a waddling gait, progressive periosteal and
      endosteal sclerosis of the diaphyses of the long bones and sclerosis of the skull
      base. Mutations in the transforming growth factor (TGF)-beta1 gene on chromosome
      19q13.1 have been reported to cause this disorder. The diagnosis of PDD/CED in
      this family was confirmed at the molecular level by detection of a C-to-T
      transition at position 466, leading to an arginine-to-cysteine amino acid change
      (position 156) in exon 2 of the transforming growth factor-beta1 (TGFB1) gene.

PMID- 15959622
TI  - Use of antidepressants by pregnant women: evaluation of perception of risk,
      efficacy of evidence based counseling and determinants of decision making.
AB  - BACKGROUND: The World Health Organization predicts that by 2012, depression will
      be the number one disease in the world. Thus, many women who become pregnant will
      require treatment with antidepressants. We are aware that women and their health
      care providers remain hesitant to prescribe and take these drugs during
      pregnancy, despite evidence of the relative safety. OBJECTIVES: 1) To determine
      perception of risk of antidepressant drugs by pregnant women with depression, 2)
      to determine the efficacy of evidence-based counseling, and 3) to identify
      determinants that influence women in their decision making regarding the
      continuation/discontinuation of antidepressants during pregnancy. METHODS: Women
      who called The Motherisk Program requesting information about the safety of an
      antidepressant during pregnancy were compared with two other groups: 1) Women who
      called about antibiotic use (i.e., non-teratogenic drugs used short-term) and 2)
      women who called about gastric medications (i.e., non-teratogenic drugs used long
      term). Their perception of risk was measured before and after evidenced-based
      information was given and determinants of decision making was also evaluated.
      RESULTS: We recruited 100 women taking antidepressants during pregnancy and 100
      in each comparison group. Despite receiving evidence-based reassuring
      information, 15% of antidepressant users, compared to 4% using gastric drugs and
      1% using antibiotics, chose to discontinue their medication. The main
      determinants of decision making were based on: information received prior to
      calling Motherisk, family and friends advice, the internet, sequence of advice
      given and if a women was undecided at the time of call. CONCLUSIONS: Women
      continue to fear taking antidepressants during pregnancy, more so than non
      psychiatric drugs, however, evidence based counseling can lower this fear,
      although not totally. Deciding whether to continue to take a medication or not
      during pregnancy, is a complex decision for women and their healthcare providers
      to make.

PMID- 15959621
TI  - The relationship of vitamin D status to bone mineral density in an Italian
      population of postmenopausal women.
AB  - Several authors have found a relationship between vitamin D status and bone
      mineral density (BMD). To our knowledge, no previous studies on this topic have
      been carried out on the Italian postmenopausal population. We studied this
      relationship retrospectively in 156 Italian postmenopausal women. We also
      investigated the relationship between parathyroid hormone (PTH) and BMD.
      Measurements of BMD were taken at the lumbar spine and upper femur by dual X-ray
      absorptiometry. Serum 25(OH)D (calcidiol), 1,25(OH)2D (calcitriol), PTH, calcium,
      phosphorus, creatinine, osteocalcin and urinary calcium and phosphorus were
      measured according to the current laboratory methods of analysis. We found a
      positive statistically significant correlation between BMD, both at the spine and
      hip, and 25(OH)D, and a negative statistically significant correlation between
      BMD and PTH. No statistically significant correlation was found between BMD and
      1,25(OH)2D. Crude logistic regression showed age, 25(OH)D and PTH were
      significant predictors of low BMD, while 1,25(OH)2D was not. Backward logistic
      regression showed 25(OH)D was the best predictive model for spine osteoporosis
      together with age, and on its own it was the best predictive model for femoral
      neck osteoporosis.

PMID- 15959623
TI  - Neonatal outcomes in offspring of women with anxiety and depression during
      pregnancy. A linkage study from The Nord-Trondelag Health Study (HUNT) and
      Medical Birth Registry of Norway.
AB  - BACKGROUND: The presence of mental disorder during pregnancy could affect the
      offspring. AIMS: To examine the effects of anxiety disorder and depression in
      pregnant women on neonatal outcomes, and to compare neonatal outcomes between
      offspring of attendees and non-attendees in a general population-based health
      survey. METHOD: Pregnant women (n = 680) were identified from the population
      based health study of Nord-TrOndelag County (HUNT-2) by linkage with the Medical
      Birth Registry of Norway. The women rated themselves on the Hospital Anxiety and
      Depression Rating Scale (HADS). Outcome variables were gestational length, birth
      weight, and Apgar scores. RESULTS: HADS-defined anxiety disorder during pregnancy
      was associated with lower Apgar score at one minute (score < 8; odds ratio =
      2.27; p = .03) and five minutes (score < 8; odds ratio = 4.49; p = .016). No
      confounders were identified. Anxiety disorder and depression during pregnancy was
      not associated with low birth weight or preterm delivery. Offspring of non
      attendees had a lower birth weight (77 g; t = 3.27; p = 0.001) and a shorter
      gestational length (1.8 days; t = 2.76; p = 0.006) than that of offspring of
      attendees, a difference that may be explained by a higher load of psychosocial
      risk factors among the non-attendees. CONCLUSION: In our study that may be biased
      towards the healthier among pregnant women, anxiety disorder or depression during
      pregnancy were not strong risk factors for adverse neonatal outcomes although low
      Apgar score in offspring of women with anxiety disorder may indicate poor
      neonatal adaptation.

PMID- 15959624
TI  - The course of anxiety and depressive symptoms in Nigerian postpartum women.
AB  - Postnatal depression is mostly studied within the first 12 weeks postpartum and
      postnatal anxiety neglected. Using the Zung's self rating anxiety and depression
      scales in a repeated cross sectional study of postpartum women we found both
      anxiety and depressive symptoms more in first 8-weeks postpartum with a gradual
      decline in later postpartum period. Anxiety is more common than depression in the
      first 4-weeks with reversal of the trend subsequently. Both symptoms may persist
      till late postpartum period.

PMID- 15959625
TI  - Inpatient treatment of women with postpartum psychiatric disorders--the role of
      the male partners.
AB  - Postpartum psychiatric disorders are stressful events for all members of the
      family. The male partners contribute to the women's coping process. To evaluate
      the men's supportive function we investigated 31 partners of 34 women with
      postpartum psychiatric disorders. Three male partners were unreachable although
      we tried to contact them intensively. All the women examined were in-patients of
      a mother-child unit after delivery. The men's behaviour in the relationship, in
      their role as a partner, and as a father were rated in a categorical-qualitative
      way. We found that nearly one third of the male partners can be described as
      "supportive". This finding strongly correlates with the subjective experience of
      the corresponding wives of being supported by the male partners. However in the
      subgroup of women who had already suffered from prepartum psychiatric disorders
      with onset before index-delivery, the majority of the male partners were rated
      and experienced as "non-supportive". Additionally, ten of these men suffered from
      several DSM-IV/ICD-10 based psychiatric disorders themselves. Using the
      standardised questionnaire "operationalisierte psychodynamische Diagnostik" (OPD)
      we describe the higher ego-strength of the supportive male partners. We found
      that there was a reduction in the length of stay in the hospital in the families
      with supportive male partners.

PMID- 15959627
TI  - The molecular mechanism of actinomycin D in preventing neointimal formation in
      rat carotid arteries after balloon injury.
AB  - The pathological mechanism of restenosis is primarily attributed to excessive
      proliferation of vascular smooth muscle cells (SMC). Actinomycin D has been
      regarded as a potential candidate to prevent balloon injury-induced neointimal
      formation. To explore its molecular mechanism in regulating cell proliferation,
      we first showed that actinomycin D markedly reduced the SMC proliferation via the
      inhibition of BrdU incorporation at 80 nM. This was further supported by the G1
      phase arrest using a flowcytometric analysis. Actinomycin D was extremely potent
      with an inhibitory concentration IC50 at 0.4 nM, whereas the lethal dose LD50 was
      at 260 microM. In an in vivo study, the pluronic gel containing 80 nM and 80
      microM actinomycin D was applied topically to surround the rat carotid
      adventitia; the thickness of neointima was substantially reduced (45 and 55%,
      respectively). The protein expression levels of proliferating cell nuclear
      antigen (PCNA), focal adhesion kinase (FAK), and Raf were all suppressed by
      actinomycin D. Extracellular signal-regulated kinases (Erk) involved in cell
      cycle arrest were found to increase by actinomycin D. These observations provide
      a detailed mechanism of actinomycin D in preventing cell proliferation thus as a
      potential intervention for restenosis.

PMID- 15959626
TI  - Bacterial diversity and carbonate precipitation in the giant microbialites from
      the highly alkaline Lake Van, Turkey.
AB  - Lake Van harbors the largest known microbialites on Earth. The surface of these
      huge carbonate pinnacles is covered by coccoid cyanobacteria whereas their
      central axis is occupied by a channel through which neutral, relatively Ca
      enriched, groundwater flows into highly alkaline (pH approximately 9.7) Ca-poor
      lake water. Previous microscopy observations showed the presence of aragonite
      globules composed by rounded nanostructures of uncertain origin that resemble
      similar bodies found in some meteorites. Here, we have carried out fine-scale
      mineralogical and microbial diversity analyses from surface and internal
      microbialite samples. Electron transmission microscopy revealed that the
      nanostructures correspond to rounded aragonite nanoprecipitates. A progressive
      mineralization of cells by the deposition of nanoprecipitates on their surface
      was observed from external towards internal microbialite areas. Molecular
      diversity studies based on 16S rDNA amplification revealed the presence of
      bacterial lineages affiliated to the Alpha-, Beta- and Gammaproteobacteria, the
      Cyanobacteria, the Cytophaga-Flexibacter-Bacteroides (CFB) group, the
      Actinobacteria and the Firmicutes. Cyanobacteria and CFB members were only
      detected in surface layers. The most abundant and diverse lineages were the
      Firmicutes (low GC Gram positives). To the exclusion of cyanobacteria, the
      closest cultivated members to the Lake Van phylotypes were most frequently
      alkaliphilic and/or heterotrophic bacteria able to degrade complex organics.
      These heterotrophic bacteria may play a crucial role in the formation of Lake Van
      microbialites by locally promoting carbonate precipitation.

PMID- 15959628
TI  - Modification of oxidative stress by pioglitazone in the heart of alloxan-induced
      diabetic rabbits.
AB  - The study was undertaken to analyze the effect of pioglitazone on superoxide
      dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px),
      glutathione reductase (GSSG-R), glutathione (GSH), ascorbic acid (AA), lipid
      peroxidation products (LPO) and protein carbonyl groups (PCG) in the heart of
      alloxan-induced diabetic rabbits after 4 and 8 weeks of pioglitazone treatment.
      In diabetic animals, Cu, Zn-SOD and CAT were elevated by 60 and 55%, and 90 and
      77% as compared to controls at 4 and 8 weeks, respectively. GSH-Px, GSSG-R and
      GSH were diminished by 11, 14 and 33% as compared to controls at 4 or 8 weeks. AA
      was diminished by 52 and 41%. At P <0.05, pioglitazone normalized the activities
      of Cu, Zn-SOD, GSH-Px and GSSG-R. The activity of CAT was modified as compared to
      diabetic non-treated rabbits. After pioglitazone treatment, GSH and AA were
      increased as compared to diabetic non-treated animals. In diabetic rabbits, LPO
      was elevated by 52 and 111% and normalized by pioglitazone treatment. PCG was
      elevated by 72 and 133% and diminished as compared to diabetic non-treated
      animals at 8 weeks. The study shows that pioglitazone reduces oxidative stress in
      the heart of diabetic rabbits. In therapy, similar action can improve the
      cardiovascular system of diabetic patients.

PMID- 15959629
TI  - Serum total sialic acid levels in smokers and users of smokeless tobacco in form
      of oral powder (Maras powder).
AB  - Smokeless tobacco (ST) is widely used as chewing tobacco and as oral snuff in the
      world. Also, in Kahramanmaras, a city in Southern Turkey, ST used as 'oral
      powder' or 'Maras Powder' is consumed widely instead of cigarette smoking. The
      aim of this study was to search the effect of ST use on serum total sialic acid
      (TSA) and to compare the serum TSA levels in smokers and ST users. The study was
      performed at the Department of Chemistry-Biochemistry, University of Kahramamaras
      Sutcu Imam, Turkey, in 2003. Serum samples obtained from smokers (Group I), Maras
      powder users (Group II), and healthy control subjects (Group III) who were
      nonsmokers and nonusers ST. Individuals who were smokers and ST users were
      classified into subgroups with respect to amount of consumed cigarette or oral
      powder. Serum TSA was measured with the Denny's colorimetric method. The TSA
      concentrations were significantly higher in the sera of smokers (p < 0.001) and
      Maras powder users (p < 0.001) than those of control subjects. The mean serum TSA
      level was found to be lowest in the control group and highest in the Maras Powder
      users. But, there was no significant difference in serum TSA levels between
      smokers and Maras powder users (p > 0.05). We can conclude from the results
      obtained that serum TSA was affected by ST use as seen in smokers. This finding
      may be an indication of harmful effects of ST use as Maras powder as well as
      cigarette smoking.

PMID- 15959630
TI  - Diazoxide ameliorates microcirculatory disturbances through PKC-dependent pathway
      in I/R-injured rat cremaster muscles.
AB  - Diazoxide is a selective mitochondria ATP-sensitive potassium (K(ATP)) channel
      opener, which has been reported to preserve the microvascular integrity of
      ischemia-reperfusion (I/R)-injured tissues. Our study aimed to assess diazoxide's
      effects on I/R-injured cremaster muscles and to further elucidate its underlying
      mechanisms. Male Sprague Dawley (SD) rats were randomized (n = 8 per group) into
      four groups: sham-operated control group, I/R group (4 h of pudic epigastic
      artery ischemia followed by 2 h of reperfusion), diazoxide + I/R group, and
      chelerythrine (PKC inhibitor)+diazoxide+I/R group. Microscopically, we observed
      that I/R markedly increased the number of rolling, adhering, and transmigrating
      leukocytes. I/R also markedly decreased the number of functional capillaries.
      Biochemically, we found that I/R significantly increased TNF-alpha, E-selectin,L
      selectin and P-selectin expressions. However, I/R did not cause significant
      changes in ICAM-1 and PECAM-1 expressions. On the other hand, in I/R + diazoxide
      group, we found that diazoxide reduced the number of rolling, adhering, and
      transmigrating leukocytes. Furthermore, biochemical study revealed that diazoxide
      caused only a decrease in L-selectin expression but had no effect on TNF-alpha, E
      selectin, P-selectin, ICAM-1, and PECAM-1 expressions. Finally, in chelerythrine
      + diazoxide + I/R group, we observed that diazoxide's protective effects were
      blocked by the addition of chelerythrine. Diazoxide's ability to protect against
      I/R injury was confirmed by the observation that it reduced the number of
      rolling, adhering, and transmigrating leukocytes, and increased the number of
      functional capillaries. Our results indicated that diazoxide operated via a PKC
      dependent pathway to achieve protection against I/R injury.

PMID- 15959631
TI  - Protein and m-RNA expression of farnesyl-transferases, RhoA and RhoB in rat liver
      hepatocytes: action of perillyl alcohol and vitamin A in vivo.
AB  - We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor
      perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA
      and protein expression of farnesyltransferases (FTases alpha and beta subunits)
      and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined
      administration of POH and vitamin A induced a sharp decrease in FTase alpha
      protein after 96 h, suggesting an involvement not only of farnesyltransferases
      but also of geranylgeranyltransferases, which share the FTase alpha protein.
      FTase beta protein did not decrease. POH plus vitamin A, in contrast with POH or
      vitamin A alone, induced a decrease in RhoB protein, probably because of
      different cleavages. No modification was observed in RhoA protein. Vitamin A
      alone increased RhoB m-RNA and protein expression. As one of the functions of
      RhoB is cell polarisation, these data support our previous hypothesis of a
      polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As
      the behaviours of m-RNAs and proteins in this study were often different,
      cytoplasmic metabolic pathways must be considered for the parameters studied. The
      behaviour of Rho B, which is thought to have an antioncogene function, is
      discussed in view of its isoprenylated forms in the membranes. These preliminary
      findings stress the need, when studying the association of two isoprenoids in
      cancer therapy, to consider normal as well as tumour-bearing animals.

PMID- 15959632
TI  - Perceived relative attractiveness of facial profiles with varying degrees of
      skeletal anomalies.
AB  - OBJECTIVE: The objective of this study was to answer the following questions: Are
      profiles of Class I patients perceived as more attractive than profiles of Class
      II or Class III patients in Germany today? How pronounced must a skeletal
      malocclusion be to be perceived as less attractive? Are there differences in
      perception between dentists and laypersons? MATERIAL AND METHOD: For the present
      study we examined seven patients with skeletal Class I, orthognathic maxillae and
      mandibles, and straight average faces (ideal biometric face as defined by A. M.
      Schwarz). Using the Onyx Ceph software, their profile lines were modified to
      reflect three different Class II profile variants and three different Class III
      profile variants. The 49 profiles thus obtained were assigned to two groups.
      Group 1 comprised the seven straight average faces and the first part of the
      retrognathic and prognathic profile variants. Group 2 comprised the same seven
      straight average faces and the remaining retrognathic and prognathic profile
      variants. Both groups of faces were scored by 130 laypersons and 126 dentists.
      RESULTS: Both groups of observers perceived the seven straight average faces
      similarly both in the first and second (subsequent) scoring rounds. The straight
      average face was perceived as most attractive by laypersons (mean, 5.48; 95%
      confidence interval (CI:) 5.33-5.60) and dentists (mean, 5.44; 95% CI, 5.28-5.50)
      alike, followed by the mildest variant of the retrognathic face (laypersons,
      mean, 4.85; 95% CI, 4.68-5.01; dentists, mean, 4.98; 95% CI, 4.81-5.10). Dentists
      differentiated more clearly by degree of skeletal malocclusion than did
      laypersons. Both groups alike perceived the extreme variant of the prognathic and
      retrognathic profile lines as the least attractive. Grouping the subjects by
      gender yielded only minor differences in perception. CONCLUSION: The straight
      average face is perceived as most attractive by representative German populations
      today. Dentists make clearer gradual distinctions in their perceptions than do
      laypersons.

PMID- 15959633
TI  - Investigation of craniofacial morphology in patients with hypo- and oligodontia.
AB  - AIM: This cephalometric study was performed with the intention to qualify and
      quantify differences between the craniofacial morphology in persons with
      congenitally missing teeth (hypo- and oligodontia) in comparison with the
      craniofacial morphology in persons without missing teeth. PATIENTS AND METHODS:
      Lateral cephalograms of 42 (21 female, 21 male) patients were traced. Patient
      mean age at the time the radiographs were taken was 13.39+/-7.30 years. The
      sample was divided into two groups: There were 22 patients in the oligodontia
      group (11 f, 11 m). The group of those with hypodontia contained 20 persons (10
      f, 10 m). The growth study by Riolo et al. served as the control. RESULTS:
      Patients with congenitally missing teeth compared to those with complete
      dentition showed reduced maxillary and mandibular length (p<0.001). The mandible
      was prognathic, the chin positioned more anteriorly (angleSNB p<0.05, angleSNPog
      p<0.01). The overall anterior face height was noticeably lower as a result of the
      shortening of both upper anterior and lower anterior face heights (p<0.001).
      Comparison between patients with oligodontia and those with hypodontia revealed
      statistically significant differences in only two dentoalveolar measurements.
      CONCLUSION: There were significant morphologic differences between patients with
      congenitally missing teeth and patients with complete dentition. Additional
      differentiation between oligodontia and hypodontia revealed only few differences.

PMID- 15959634
TI  - Development of a model for the simulation of orthodontic load on lower first
      premolars using the finite element method.
AB  - AIM: This study was undertaken to calculate the stress in the tooth, surrounding
      periodontal ligament, and in the alveolar bone when a lower first premolar is
      subjected to intrusion or torque movement using a constant moment. Root
      resorptions occur even when very low forces and moments are used in orthodontic
      therapy. It is therefore of great interest to determine and measure the stress
      that occurs under particular treatment conditions in the periodontal ligament.
      MATERIAL AND METHODS: In this study, three finite element calculations were
      carried out with a realistic 3D model developed by CT data that consisted of a
      lower premolar, the surrounding periodontal ligament and alveolar bone. In close
      reference to the in-vivo experiments carried out by Faltin et al. in Sao Paulo,
      Brazil, our model was subjected to an intrusive force on the premolar of 0.5 N
      and a lingual root torque of 3 Nmm. RESULTS: The three main stress directions and
      hydrostatic stress were quantified in all the surrounding tissues, revealing that
      the hydrostatic stress profile in the periodontal ligament correlated closely
      with resorption findings in Faltin et al.'s patients. Resorption occurred in the
      experimental study in Brazil when the hydrostatic stress exceeded capillary blood
      pressure in the periodontal ligament. CONCLUSION: We maintain that hydrostatic
      stress represents a suitable indicator for potential root resorptions caused by
      higher forces and moments, making it a helpful tool in the development of new
      orthodontic appliances. We must of course mention that there are many factors
      other than forces that are responsible for resorptions. But at the moment, only
      the force can be influenced by the orthodontist.

PMID- 15959635
TI  - A comparison of the periodontal health of patients during treatment with the
      Invisalign system and with fixed orthodontic appliances.
AB  - OBJECTIVE: Evaluation of the periodontal health in patients during treatment with
      either fixed orthodontic appliances or the Invisalign system. STUDY DESIGN: The
      study was designed as a concomitant trial. The evaluation of the patients started
      in February 2002 and was completed in August 2003. PATIENTS AND METHODS: Thirty
      consecutive patients each with fixed orthodontic appliances and with aligners
      were examined at three consecutive control visits for their periodontal
      condition. All individuals were part of the clientele of the Department of
      Orthodontics and Dentofacial Orthopedics of the Charite Berlin. The parameters
      evaluated were the modified Gingival Index, modified Plaque Index, modified
      Papillary Bleeding Index, and sulcus probing depth. The first three indices were
      recorded alternatively buccally and lingually in all permanent teeth from central
      incisor to first molar: buccally in the maxillary right and the mandibular left
      quadrants, lingually in the maxillary left and mandibular right quadrants. The
      sulcus depth was measured in four areas: mesially and distally, lingually and
      buccally in the 1st molar and the 1st premolar of each quadrant. Each control
      visit was concluded with a detailed, individualized oral hygiene instruction.
      RESULTS: The modified Plaque Index was significantly lower in the Invisalign
      group overall. On the other hand, the periodontal condition of the two samples
      was nearly identical. CONCLUSION: Periodontal health is not jeopardized, even
      though the Invisalign system aligners cover all the teeth and the keratinized
      gingiva in part. This could be attributed to the fact that aligners are removable
      and thus allow unimpeded oral hygiene.

PMID- 15959636
TI  - Retrospective analysis of casts to assess cervical headgear treatment in the
      presence of vertical growth pattern.
AB  - OBJECTIVE: Does molar distalization as effected by cervical headgear increase the
      vertical dimension of occlusion in patients with vertical growth pattern?
      MATERIALS AND METHODS: A sample of 86 patients with neutral and vertical growth
      pattern in the late mixed dentition stage underwent headgear treatment. Their
      initial and intermediary casts were retrospectively analyzed for occlusal
      relationships at the maxillary first molars and degrees of overjet and overbite.
      The only cases included were those in which headgear treatment was carried on for
      at least 6 months, achieving a minimum distalization of 4 mm. The intermediary
      casts were fabricated after headgear treatment had been completed and prior to
      the initiation of multiband treatment. Patients were divided into three groups
      (N, V1 and V2) according to the degrees of vertical growth pattern, which were
      determined based on y-axis angle values. RESULTS: Grouped by degrees of vertical
      growth, the data revealed occlusal relationship changes of 6-8 mm and overjet
      reductions of 0.6-1.2 mm. The overbite changes were unexpectedly small (0-0.04
      mm). Grouped by degrees of overbite, the data revealed that headgear treatment
      increased the vertical dimension of occlusion in deep-bite patients (>4 mm),
      while giving rise to decreases in patients with overbites of <3 mm.

PMID- 15959637
TI  - Indications for digital volume tomography in orthodontics.
AB  - Disturbances in tooth eruption and tooth impactions make great demands on
      radiographic diagnostics. There is often need for radiographic images in various
      projections to assess the exact position of unerupted and impacted teeth. Digital
      volume tomography (DVT) is a method for localizing hard tissue structures such as
      bone and teeth on various planes. Moreover, it makes a three-dimensional image of
      the teeth, jaws and the viscerocranium possible. From an orthodontic point of
      view, digital volume tomography is indicated to detect impacted and ectopic teeth
      and to demonstrate the amount of bone available for orthodontic tooth movement.
      In patients with cleft lip and palate, DVT can be used to visualize the size of
      the alveolar cleft and to evaluate the position and development of multiple
      teeth, as these patients often suffer from disturbances in tooth eruption.

PMID- 15959638
TI  - Age-related changes in the midpalatal suture. A histomorphometric study.

PMID- 15959639
TI  - NSGC foundations-then, now, and tomorrow.
AB  - This 2004 Presidential Address was presented at the annual education conference
      of the National Society of Genetic Counselors in Washington DC on October 9,
      2004.

PMID- 15959640
TI  - A practical account of autonomy: why genetic counseling is especially well suited
      to the facilitation of informed autonomous decision making.
AB  - In genetic counseling, facilitation of autonomous decision-making is seen as a
      primary aim and respect for autonomy is used to justify a nondirective counseling
      approach whereby clients are free to make their own choices after being given all
      necessary information. However in the genetic counseling literature, autonomy as
      a concept appears to be interpreted variably and often narrowly. We offer a
      practical account of autonomy that is coherent, consistent and philosophically
      defensible for the genetic counseling setting. At the same time we demonstrate
      how nondirective counseling may serve to frustrate rather than facilitate client
      autonomy. We suggest that promoting purposeful dialogue rather than counseling
      that is nondirective is more conducive to client autonomy.

PMID- 15959641
TI  - Psychodynamic theory and counseling in predictive testing for Huntington's
      disease.
AB  - This paper revisits psychodynamic theory, which can be applied in predictive
      testing counseling for Huntington's Disease (HD). Psychodynamic theory has
      developed from the work of Freud and places importance on early parent-child
      experiences. The nature of these relationships, or attachments are reflected in
      adult expectations and relationships. Two significant concepts, identification
      and fear of abandonment, have been developed and expounded by the psychodynamic
      theorist, Melanie Klein. The processes of identification and fear of abandonment
      can become evident in predictive testing counseling and are colored by the
      client's experience of growing up with a parent affected by Huntington's Disease.
      In reflecting on family-of-origin experiences, clients can also express implied
      expectations of the future, and future relationships. Case examples are given to
      illustrate the dynamic processes of identification and fear of abandonment which
      may present in the clinical setting. Counselor recognition of these processes can
      illuminate and inform counseling practice.

PMID- 15959642
TI  - How do obstetric providers discuss referrals for prenatal genetic counseling?
AB  - To investigate referrals of pregnant women to genetic counseling, we analysed
      transcripts from audiotaped first prenatal visits of 104 patients (72 actual
      patient visits and 32 simulated patient visits) with 32 providers (obstetricians
      and nurse-midwives). All patients had at least one indication for referral. Only
      10% of visits with actual patients included a genetic counseling referral. When
      genetic counseling was discussed, it was only briefly described, primarily as an
      information session. This study shows that the majority of pregnant women with an
      indication for referral for genetic counseling are not referred. In addition,
      obstetric providers' inadequate descriptions of prenatal genetic counseling may
      result in women being poorly prepared for genetic counseling sessions.

PMID- 15959644
TI  - Facilitating family communication about predictive genetic testing: probands'
      perceptions.
AB  - The responsibility of informing relatives that predictive genetic testing is
      available often falls to the proband. Support is required during this process,
      however the perceived utility of genetic counseling and other strategies to
      facilitate communication have not been explored. We investigated the experiences
      of 12 individuals with hereditary nonpolyposis colorectal cancer (HNPCC) in a
      semistructured telephone interview. Respondents informed their immediate family
      about the availability of genetic testing, however many more-distant relatives
      were not directly informed. Respondents were mostly satisfied with the way they
      told family members about testing and had mixed views about the usefulness of
      genetic counseling. Gender differences were observed, with most men expressing a
      need for guidance or support in communicating to relatives. Letters and booklets
      were thought to enhance the quality of information but the provision of further
      aids is unlikely to increase the number of relatives made aware of predictive
      testing by the proband.

PMID- 15959643
TI  - Genetic counseling outcomes: perceived risk and distress after counseling for
      hereditary colorectal cancer.
AB  - Genetic counseling may turn risk information into cancer prevention behavior by
      modifying health beliefs and cancer-related distress. We assessed the effect of
      genetic counseling on these factors in 101 adult first-degree-relatives of
      colorectal cancer patients from families with known or suspected hereditary
      nonpolyposis colorectal cancer. Before counseling and once afterward, subjects
      completed self-report measures of perceived lifetime risk and cancer-distress.
      Most persons overestimated their cancer risk, and higher perceived risk was
      associated with believing that colorectal cancer cannot be prevented. Individual
      perceived risk changed after counseling, although mean perceived risk was
      unchanged. After adjusting for baseline risk, older persons and those with higher
      estimated objective cancer risk had larger postcounseling decreases. Distress
      after counseling was positively correlated with baseline distress and anxiety
      symptoms, and inversely correlated with tolerance for ambiguity. The findings
      suggest counseling interventions that should increase the likelihood of screening
      and offer hypotheses for future research.

PMID- 15959645
TI  - Emotional responses to APO E genotype disclosure for Alzheimer disease.
AB  - The purpose of our study is to assess the emotional responses to disclosing APO E
      genotype to asymptomatic older adults at increased risk for Alzheimer disease
      (AD). This is a longitudinal cohort study of volunteer subjects who were aged 50
      years or over, asymptomatic for (AD), had a family history of AD, passed a
      psychological assessment, and participated in pre- and post-test genetic
      counseling and three follow-up visits over 10 months. We analyzed responses by
      three emotional constructs: depressed, worried, and relieved. Three hundred and
      twenty-eight subjects were screened, 76 received their APO E genotype. When
      emotional responses occurred it was immediate, between baseline and the 1 month
      follow-up. Emotional reactions did not change significantly past 1 month. Our
      results suggest that for emotionally stable persons, disclosing results of their
      APO E genotype, high risk subjects did not report more depression or worry and
      low risk subjects felt relieved by knowing the results. Future studies should
      evaluate the risks of disclosure to family members involved in the diagnostic
      work-up of a relative and include subjects from a broader range of emotional
      stability and socioeconomic background.

PMID- 15959646
TI  - Experiences of prenatal diagnosis of spina bifida or hydrocephalus in parents who
      decide to continue with their pregnancy.
AB  - The current study aimed to gain an understanding of the perspectives of those
      parents provided with a prenatal diagnosis of spina bifida or hydrocephalus and
      who decided to continue with their pregnancy. Qualitative interviews were
      conducted with 15 parents who learned of their unborn child's spina bifida and/or
      hydrocephalus in the prenatal period. The interviewer asked parents about their
      experiences of receiving a prenatal diagnosis and their experience of coping
      throughout the remainder of the antenatal period. Parents' reactions and
      experiences fell into five domains: response to diagnosis, experience of medical
      systems, information gathering, decision-making regarding continuation of the
      pregnancy following diagnosis and responses of significant others. Each of these
      domains is explicated. The findings derived from the current study have
      implications for professionals who provide support to parents during the prenatal
      period. Future research needs to further explore the common and unique issues for
      parents living in both urban and rural areas.

PMID- 15959648
TI  - Genetic evaluation and counseling of couples with recurrent miscarriage:
      recommendations of the National Society of Genetic Counselors.
AB  - The objective of this document is to provide recommendations for genetic
      evaluation and counseling of couples with recurrent miscarriage (RM). The
      recommendations are the opinions of the multidisciplinary Inherited Pregnancy
      Loss Working Group (IPLWG), with expertise in genetic counseling, medical
      genetics, maternal fetal medicine, internal medicine, infectious disease,
      cytogenetics, and coagulation disorders. The IPLWG defines RM as three or more
      clinically recognized consecutive or non-consecutive pregnancy losses occurring
      prior to fetal viability (<24 weeks gestation). These recommendations are
      provided to assist genetic counselors and other health care providers in clinical
      decision-making, as well as to promote consistency of patient care, guide the
      allocation of medical resources, and increase awareness of the psychosocial and
      cultural issues experienced by couples with RM. The IPLWG was convened with
      support from the March of Dimes Western Washington State Chapter and the
      University of Washington Division of Medical Genetics. The recommendations are
      U.S. Preventive Task Force Class III, and are based on clinical experiences,
      review of pertinent English-language published articles, and reports of expert
      committees. This document reviews the suspected causes of RM, provides
      indications for genetic evaluation and testing, addresses psychosocial and
      cultural considerations, and provides professional and patient resources. These
      recommendations should not be construed as dictating an exclusive course of
      medical management, nor does the use of such recommendations guarantee a
      particular outcome. The professional judgment of a health care provider, familiar
      with the circumstances of a specific case, should always supersede these
      recommendations.

PMID- 15959649
TI  - Disability rights, prenatal diagnosis and eugenics: a cross-cultural view.
AB  - This paper considers the disability rights critique of genetic testing in the
      context of different communities and the issue of nondirectiveness. Despite the
      wide usage of genetic diagnosis in Israel, no public debate has emerged there
      concerning disability rights and prenatal testing. The common attitude that
      emerged from interviews with Israeli representatives of organizations "of'' and
      "for'' people with genetic diseases and congenital disabilities can be described
      as a two-fold view of disability: support of genetic testing during pregnancy,
      and support of the disabled person after birth. This two-fold view is explained
      as a secular construction situated in legal, economic and cultural contexts. The
      paper concludes by considering the implications of the "two-fold view'' of
      disability for the profession of genetic counseling. It is argued that awareness
      of the existence of conflicting views among clients--such as the view of the
      'disability critique' as well as of the "two-fold view of disability''--should
      strengthen the significance of nondirectiveness.

PMID- 15959650
TI  - Racial-ethnic differences in genetic amniocentesis uptake.
AB  - The objective of this study was to determine the role of health beliefs in
      genetic amniocentesis acceptance in a diverse racial-ethnic population.
      Participants completed a previously-validated questionnaire consisting of three
      sections: (1) demographics, (2) amniocentesis knowledge, and (3) health beliefs,
      which assessed perceived susceptibility, seriousness of potential impact,
      benefits of testing, and barriers to testing. The results showed that Hispanic
      women were less likely to accept amniocentesis (51.5% vs. Caucasian 82.8%,
      African American 82.9%, Asian 82.8%). Education level was the only demographic
      factor higher among acceptors. Women who accepted amniocentesis had higher
      perceived seriousness, susceptibility, and benefits HBM scores and higher
      knowledge scores than women who declined. HBM scores and knowledge predicted the
      amniocentesis decision correctly 91.5% of the time. Individual health beliefs and
      knowledge play a greater role in genetic amniocentesis acceptance than do
      demographic factors such as race-ethnicity.

PMID- 15959651
TI  - Evaluating genetic counseling: client expectations, psychological adjustment and
      satisfaction with service.
AB  - Periodic evaluations of genetic counseling services are useful for determining
      the effectiveness of counseling in meetings its psycho-educational aims, as well
      as identifying where improvements to the service may be made. This study aimed to
      evaluate the genetic counseling services provided by Genetic Services of Western
      Australia (GSWA) to determine the impact of counseling on client expectations,
      satisfaction with the service, and psychological adjustment, defined as wellbeing
      and perceived personal control (PPC). A total of 122 clients participated in a
      self-administered survey conducted pre- and post-counseling. Client expectations
      of the service as a means of providing information were met, and opportunities
      for counselors to meet client's expectations of psychological support were
      identified. Furthermore, counseling was found to maintain and enhance
      psychological wellbeing of clients. The role of counseling in facilitating the
      development of PPC was a key contributor to a high sense of satisfaction in
      clients.

PMID- 15959652
TI  - Men's decision-making about predictive BRCA1/2 testing: the role of family.
AB  - Men who have a family history of breast and/or ovarian cancer may be offered a
      predictive genetic test to determine whether or not they carry the family
      specific BRCA1/2 mutation. Male carriers may be at increased risk of breast and
      prostate cancers. Relatively little is known about at-risk men's decision-making
      about BRCA1/2 testing. This qualitative study explores the influences on male
      patients' genetic test decisions. Twenty-nine in-depth interviews were undertaken
      with both carrier and noncarrier men and immediate family members (17 male
      patients, 8 female partners, and 4 adult children). These explored family
      members' experiences of cancer and genetic testing, decision-making about
      testing, family support, communication of test results within the family, risk
      perception and risk management. Implicit influences on men's testing decisions
      such as familial obligations are examined. The extent to which other family
      members--partners and adult children--were involved in testing decisions is also
      described. It is demonstrated that mothers of potential mutation carriers not
      only perceive themselves as having a right to be involved in making this
      decision, but also were perceived by their male partners as having a legitimate
      role to play in decision-making. There was evidence that (adult) children were
      excluded from the decision-making, and some expressed resentment about this. The
      implications of these findings for the practice of genetic counseling are
      discussed.

PMID- 15959653
TI  - Negotiating responsibility: case studies of reproductive decision-making and
      prenatal genetic testing in families facing Huntington disease.
AB  - Three case studies are presented to further our understanding of how
      responsibility is negotiated in families when making decisions about genetic
      risk. These draw on a model of responsibility generated in a study of
      reproductive decision-making in families facing Huntington disease (HD) to
      illustrate the impact of prenatal testing on this process. This involves
      analyzing: how people present themselves as acting responsibly whether or not
      they utilize genetic testing; who they feel responsible to in their family and
      elsewhere; the impact that testing has on these relationships; and, how
      negotiating responsibility changes over time with repeated use of prenatal
      testing, changing risk status and maturational changes. Two key findings are: how
      decision-making is perceived can become as important as what is decided; and, how
      responsibility is negotiated depends on which of these relationships are
      prioritized. Implications of the findings for clinical practice are noted and
      suggestions made for further applications of the model.

PMID- 15959654
TI  - Assessment of the use and feasibility of video to supplement the genetic
      counseling process: a cancer genetic counseling perspective.
AB  - Cancer genetic counselors use a variety of teaching modalities for patient
      education. This survey of cancer genetic counselors assessed their use of
      educational videos and their recommendations for content of future videos. Thirty
      percent of respondents use videos for patient education. Cited benefits included
      reinforcement of information for clients and increased counselor efficiency. Of
      the 70% who do not use videos, predominant barriers included the perceived lack
      of an appropriate video, lack of space and/or equipment, and concern that videos
      are impersonal. Most respondents desired a video that is representative of the
      genetic counseling session, but emphasized the importance of using broad
      information. Content considered critical included the pros and cons of genetic
      testing, associated psychosocial implications, and genetic discrimination. The
      results of this exploratory study provide data relevant for the development of a
      cancer genetics video for patient education, and suggestions are made based on
      aspects of information processing and communication theories.

PMID- 15959656
TI  - Turning darkness into light. A new landmark study on the treatment of adolescent
      depression. Comments on the TADS study.

PMID- 15959657
TI  - Informant, gender and age differences in ratings of adolescent problem behaviour.
AB  - The aim of this study was to determine gender and age differences and agreement
      among the reports of adolescent problem behaviour by parents, teachers, and
      adolescents themselves. For 1,122 11- to 18-year-olds, reports by parents,
      teachers, and adolescents were obtained. Multivariate regressions were performed
      to investigate the effect of informant, gender, and age on problem behaviour.
      Adolescents reported higher levels of problems than parents and teachers for all
      types of behaviour. Parents reported higher levels of problem behaviour than
      teachers. Gender differences among informants were dependent on type of problem
      behaviour. With increasing age, scores of adolescents, parents, and teachers
      diverged for most types of problems, with larger differences for older
      adolescents than for younger adolescents. Norms for adolescents need age
      adjustments for reports by adolescents, parents, and teachers. To obtain a
      complete view on children's problem behaviours information from multiple
      informants and differences among them is needed.

PMID- 15959658
TI  - Global consensus on ADHD/HKD.
AB  - A Global ADHD Working Group of experienced clinicians and researchers was
      gathered to review the latest evidence, discuss current best practice in the
      treatment of attention-deficit/hyperactivity disorder (ADHD), and make a
      statement based on consensus. The statement aims to re-affirm ADHD as a valid
      disorder that exists across different cultures, has a significant global impact,
      and should be diagnosed and effectively treated wherever it occurs. ADHD is one
      of the most common neurobehavioural disorders of childhood and impacts on many
      aspects of development, including social, emotional and cognitive functioning, in
      the home and school environment. Although these findings are from developed
      countries, the impact in developing countries is likely to be similar. There is
      strong supportive evidence for the validity of ADHD as a syndrome with
      neurobiological aspects, and complex genetic factors are primarily implicated in
      the aetiology. Accurate diagnosis and measurement of impairment is important to
      enable appropriate and successful management of symptoms. ADHD is a persistent
      condition that needs to be treated and monitored over time. The evidence
      supporting medication-based interventions (such as methylphenidate) is strong and
      consensus treatment algorithms to guide the multimodal treatment of ADHD, alone
      and in combination with common comorbidities, are suggested.

PMID- 15959659
TI  - Subtypes of autism by cluster analysis based on structural MRI data.
AB  - The aim of our study was to subcategorize Autistic Spectrum Disorders (ASD) using
      a multidisciplinary approach. Sixty four autistic patients (mean age 9.4+/-5.6
      years) were entered into a cluster analysis. The clustering analysis was based on
      MRI data. The clusters obtained did not differ significantly in the overall
      severity of autistic symptomatology as measured by the total score on the
      Childhood Autism Rating Scale (CARS). The clusters could be characterized as
      showing significant differences: Cluster 1: showed the largest sizes of the genu
      and splenium of the corpus callosum (CC), the lowest pregnancy order and the
      lowest frequency of facial dysmorphic features. Cluster 2: showed the largest
      sizes of the amygdala and hippocampus (HPC), the least abnormal visual response
      on the CARS, the lowest frequency of epilepsy and the least frequent abnormal
      psychomotor development during the first year of life. Cluster 3: showed the
      largest sizes of the caput of the nucleus caudatus (NC), the smallest sizes of
      the HPC and facial dysmorphic features were always present. Cluster 4: showed the
      smallest sizes of the genu and splenium of the CC, as well as the amygdala, and
      caput of the NC, the most abnormal visual response on the CARS, the highest
      frequency of epilepsy, the highest pregnancy order, abnormal psychomotor
      development during the first year of life was always present and facial
      dysmorphic features were always present. This multidisciplinary approach seems to
      be a promising method for subtyping autism.

PMID- 15959660
TI  - Psychosocial problems among immigrant and non-immigrant children--ethnicity plays
      a role in their occurrence and identification.
AB  - BACKGROUND: This study aims to examine a) the prevalence of psychosocial problems
      and b) the association between parent-reported problems and the identification by
      doctors and nurses (child health professionals, CHP) working in preventive child
      health care, among immigrant and non-immigrant children. METHODS: CHPs examined
      4,098 children aged 5 through 15 years (response: 90.1%) and interviewed parents
      and children during their routine health assessments in 19 Child Healthcare
      Services across the Netherlands, serving nearly all school-aged children
      routinely. The Child Behavior Checklist (CBCL) was completed by the parents. We
      compared five ethnic groups: indigenous Dutch, economic immigrants, immigrants
      from (former) Dutch colonies, from other non-industrialised, and from other
      industrialised countries. RESULTS: The prevalence of parent-reported problems on
      the CBCL is higher among children from former Dutch colonies and economic
      immigrant children than among indigenous children, especially regarding
      internalizing problems (odds ratios (OR); 95% confidence interval: 1.84; 1.03 to
      3.29, and 2.52; 1.46 to 4.34). CHPs identified more problems among economic
      immigrant children (OR: 1.62; 1.01 to 2.60). Regarding associations, rates of CHP
      identified problems were higher among indigenous children with clinical compared
      with normal CBCL Total Problems scores (OR: 6.90; 5.27 to 9.03), but not among
      economic immigrant children (OR: 0.73; 0.16 to 3.21). CONCLUSIONS: Psychosocial
      problems occur more frequently among some immigrant groups. CHP identification of
      psychosocial problems is poorly associated with parent report regarding economic
      immigrant children. This needs to be improved in order to provide better care.

PMID- 15959661
TI  - Prediction of adolescent outcome in children with disruptive behaviour disorders-
      a study of neurobiological, psychological and family factors.
AB  - In this preliminary study we explored the predictive influence of various family,
      psychological, demographic, and neurobiological characteristics on the
      persistence of antisocial behaviour in adolescence. Existing data were combined
      with case-records in a sample of 47 disruptive behaviour disordered (DBD)
      children who had been treated in in-patient and/or day-treatment units when they
      were between seven to 12 years old. Parent-rated and self-rated externalizing
      problem scores and the presence of a DBD diagnosis served as the outcome measures
      in adolescence. We used linear regression analyses to examine the predictors of
      adolescent outcome. A lower basal skin conductance level (SCL) was repeatedly
      found to predict poor adolescent outcome, either when rated by parents or by
      participants themselves. In addition, comorbid attention-deficit hyperactivity
      disorder, one aspect of performance on the door-opening task, and a mother of low
      socioeconomic status also predicted that a child would have more antisocial
      problems in adolescence, depending on the type of outcome measure. Results of
      this study support the fearlessness theory, according to which low activity of
      the autonomous nervous system, as manifested by low SCL, is related to the
      effectiveness of socializing punishment and accordingly to poor socialization and
      adolescent outcome.

PMID- 15959662
TI  - Functional impairment in clinical samples of Norwegian and Swedish children and
      adolescents with obsessive-compulsive disorder.
AB  - The aims of the present study were to examine OCD-related impairments in clinical
      cases of childhood OCD and to replicate and extend previous research on OCD
      related impairments. METHOD: Sixty-eight patients aged 8-17 years recruited from
      four child psychiatric outpatient clinics in Norway and Sweden with a confirmed
      DSM-IV diagnosis of OCD were included in the study. All patients and their
      parents were interviewed for diagnosis and comorbidity (KSADS),OCD symptoms and
      severity (CY-BOCS), and global impairment (CGAS). OCD-specific impairments were
      assessed by means of the Child OCD Impact Scale (COIS), a 58 item questionnaire
      with parallel parent and child versions. RESULTS: Overall, the majority of
      patients suffered from substantial impairments. The impact of OCD symptoms was
      found to be most severe at home, but impairments were also prominent in
      situations related to school and social settings. CONCLUSIONS: Our study supports
      findings of previous research suggesting multiple impacts of OCD symptoms on
      children's psychosocial functioning. We conclude that impairment issues should be
      further addressed in future research to establish a better empirical basis for
      the understanding of different aspects of OCD-related impairment.

PMID- 15959663
TI  - Suicidality in adjustment disorder--clinical characteristics of adolescent
      outpatients.
AB  - OBJECTIVE: Although a remarkable proportion of adolescents suffering from
      adjustment disorder (AD) are suicidal, few studies have documented the
      characteristics of suicidal AD patients. We examined background, psychopathology
      and treatment-related factors among suicidal adolescent AD outpatients. METHOD:
      Data on 302 consecutively referred psychiatric outpatient adolescents, aged 12-22
      years, were collected. DSM-III-R diagnoses were assigned at the end of treatment
      based on all available data. Of the patients 89 received a diagnosis of AD, 25%
      of whom showed suicide attempts, suicidal threats or ideation. RESULTS: Compared
      with non-suicidal AD patients, suicidal AD patients were characterized by
      previous psychiatric treatment (OR = 6.1), poor psychosocial functioning at
      treatment entry (OR = 16.2), suicide as a stressor (OR = 33.3), dysphoric mood
      (OR = 6.9) and psychomotor restlessness (OR = 3.7). CONCLUSIONS: Common risk
      factors for suicidality in major psychiatric disorders characterized suicidal AD
      patients. Psychiatric assessment of AD patients should include careful monitoring
      of both symptomatology and exposure to suicide of significant others.

PMID- 15959666
TI  - Intravenous immunoglobulin in neurological disorders: a mechanistic perspective.
AB  - Intravenous immunoglobulin (IVIg) has been used in the treatment of primary and
      secondary antibody deficiencies for over 25 years. It is a safe preparation with
      no long-term side effects. IVIg was first demonstrated to be effective in
      autoimmune disorders, two decades ago, in the treatment of acute immune
      thrombocytopenia. Since then, the therapeutic efficacy of IVIg has been
      established in Guillain Barre syndrome (GBS), chronic inflammatory demyelinating
      polyneuropathy (CIDP), myasthenia gravis (MG), dermatomyositis (DM), Kawasaki
      syndrome and the prevention of graft-versus-host disease in recipients of
      allogeneic bone marrow transplants and reported in a large number of other
      autoimmune and systemic inflammatory conditions.

PMID- 15959667
TI  - IVIg in myasthenia gravis, Lambert Eaton myasthenic syndrome and inflammatory
      myopathies: current status.
AB  - Intravenous immunoglobulin (IVIg) is an effective tool for the treatment of
      diseases with immune pathogenesis. This article reviews the current knowledge of
      the benefits of treating with IVIg patients with myasthenia gravis (MG), Lambert
      Eaton myasthenic syndrome (LEMS), dermatomyositis (DM), polymyositis (PM) and
      inclusion body myositis (IBM). Myasthenia gravis: Treatment of MG with IVIg was
      reported to be beneficial in a number of case series and two randomised
      controlled trials, in which efficacy was measured by clinical improvement using
      myasthenic muscle score and decrease in anti-acetylcholine receptor antibodies
      (AchRAb). According to the results, IVIg could be recommended for crisis and
      severe exacerbation. In many other clinical conditions, such as response to
      treatment of mild or moderate exacerbation, changes in steroid dosage and before
      thymectomy, IVIg has also been reported to be helpful, but no controlled trials
      to confirm its efficacy have been performed. Lambert-Eaton myasthenic syndrome: A
      placebo-controlled crossover study reported a significant clinical improvement in
      the amplitude of the resting CMAP following IVIg treatment. Further experience
      from case reports also indicates that IVIg is useful in patients with LEMS, both
      as a short- and long-term treatment, especially when immunosuppressive drugs are
      not fully effective. Inflammatory myopathies/dermatomyositis: In a double-blind
      placebo-controlled crossover trial in patients with DM resistant to other
      treatments, IVIg was shown to produce a significant increase of muscle strength
      as well as a marked improvement in immunopathological parameters in repeated
      muscle biopsies (before and after IVIg). Thus, IVIg is an important therapy in
      patients with DM resistant to other conventional therapies. Polymyositis: No
      randomised trials have been undertaken. One study showed clinical improvement and
      a reduction in the need of prednisone in patients with chronic refractory PM.
      Inclusion body myositis: Three controlled trials showed some muscle strength
      improvement, although the changes did not reach statistical significance. However
      improvement in swallowing was repeatedly observed, suggesting that some patients
      with severe dysphagia may derive a modest benefit from IVIg therapy. CONCLUSION:
      Controlled trials indicate that in MG, LEMS, and DM, IVIg at a total dose of 2
      g/kg is a highly useful therapy. Uncontrolled trials and case reports indicate
      benefit in many different clinical situations, but further clinical investigation
      is required.

PMID- 15959668
TI  - The role of IVIg in the treatment of patients with stiff person syndrome and
      other neurological diseases associated with anti-GAD antibodies.
AB  - INTRODUCTION: High-titre anti-GAD antibodies are characteristically seen in
      patients with stiff person syndrome (SPS). Other CNS disorders, rarely associated
      with high anti-GAD antibody titres, include: a) SPS-plus, a syndrome
      characterised by SPS and cerebellar ataxia; b) Batten's disease; and c) rare
      patients with epilepsy and idiopathic cerebellar ataxia. Currently, high-titre
      anti- GAD antibodies serve only as markers of an autoimmune process within the
      CNS because their pathogenic role in the afore-mentioned disorders has not been
      established. In SPS, there is evidence of autoimmune pathogenesis based on: the
      association of the disease with other autoimmune disorders or autoantibodies;
      immunogenetic background; presence of oligoclonal IgG bands in the CSF with
      increased intrathecal anti-GAD antibody synthesis and response to
      immunotherapies. SPS is the only GAD-positive CNS disease where a controlled
      study with immunotherapy has been conducted. METHODS: Sixteen anti-GAD antibody
      positive patients were randomised to receive IVIg or placebo for 3 months. After
      a washout, they crossed to the alternative therapy for another three months.
      Efficacy was based on the difference in scores of the distribution of stiffness
      index and heightened sensitivity (spasms) from baseline to the second and third
      month of the infusions. Direct treatment and carry-over effect were compared for
      both groups. RESULTS: The stiffness scores in the IVIg-randomised patients
      declined significantly from month 1 through 4, but rebounded when they crossed to
      placebo. In contrast, the scores in the placebo-randomised group remained
      constant from month 1-4 but dropped significantly after crossing to IVIg. Eleven
      patients who received IVIg became able to walk unassisted, stopped falling and
      assumed household or work duties. The duration of benefit varied from 6-12 weeks
      or up to a year. The anti-GAD(65) antibody titres declined after IVIg, but not
      after placebo. CONCLUSION: Based on a controlled study, IVIg is a safe and
      effective therapy for SPS in patients unresponsive to other agents. Whether IVIg
      has a role in the other GAD-positive patients with neurological disease, or in
      SPS patients without GAD antibodies, remains unknown.

PMID- 15959670
TI  - The 120th anniversary, Karen Horney, September 16, 1885. Karen Horney: a
      portrait.

PMID- 15959669
TI  - IVIg in idiopathic autoimmune neuropathies: analysis in the light of the latest
      results.
AB  - High-dose intravenous immunoglobulin (IVIg) is effective in the treatment of
      idiopathic autoimmune neuropathies including Guillain-Barre syndrome (GBS),
      chronic inflammatory demyelinating neuropathy (CIDP) and multifocal motor
      neuropathy (MMN), representing a useful option or, as in MMN, the gold standard
      for their treatment. In GBS, two randomised, controlled trials (RCT) showed that
      IVIg is at least as effective as plasma exchange (PE). IVIg may however be
      preferred due to its low number of contraindications and complications and the
      fact that it can be administered at any time, in any department, including
      patients with contraindications to PE, or in intensive care units. In CIDP, at
      least four RCTs have demonstrated the efficacy of IVIg in over 60% of CIDP
      patients, while two additional RCTs have shown a comparable effect to steroids
      and PE as initial treatment. As with PE, the effects of IVIg usually last a few
      weeks meaning that the majority of patients require periodic maintenance
      infusions. The lower cost and easier administration of oral steroids compared to
      IVIg may be partly compensated by the safer long-term profile of IVIg over
      steroids. In MMN, almost 80% of patients improve with IVIg, the efficacy of which
      has been confirmed by four RCTs, making of IVIg the first-choice therapy in MMN,
      for which steroids and PE are ineffective or even detrimental. Also in these
      patients, IVIg induces a rapid improvement that usually lasts only a few weeks
      and has to be maintained with periodic IVIg infusions for long periods of time,
      if not indefinitely.

PMID- 15959671
TI  - The case of David: on the couch for sixty minutes, nine years of once-a-week
      treatment.
AB  - This paper illustrates a unique case of object relations psychoanalytic
      psychotherapy on a once-a-week treatment basis. The work of developmental
      mourning that would be thought to require two to five sessions a week was
      accomplished on a once-a-week basis. The analyst adjusted the treatment hour, in
      this one case, to 60 minutes, as opposed to the 45- or 50-minute hour. When
      treatment began, the analyst made an intuitive judgment to increase the patient's
      one session a week--which the patient made clear was all he was ready to do--to
      60 minutes. The analyst made time in her practice for this 60-minute session and
      has continued with the patient using this format for 9 years of treatment. This
      had led up to the current stage of treatment, which has been so critical to the
      patient's self-integration process.

PMID- 15959672
TI  - Psychoanalytic psychotherapy for severely disturbed borderline patients:
      observations on the supervision group of psychotherapists.
AB  - The authors describe the role of a supervision group of psychotherapists within a
      wider therapeutic field for severely disturbed borderline patients. The group
      concentrates on the transference and countertransference, seen according to
      Racker's distinction between concordant and complementary identifications. The
      implications of the prevalence of the complementary identifications over the
      concordant identifications of the therapists to their patients and the resulting
      regression to primitive defense mechanisms can be counterbalanced by the group's
      integrative functioning as receiver (1) of a variety of information about the
      patient, (2) of the therapist's attempt to understand and synthesize, and (3) of
      the therapist's countertransference reactions to his patient. The major
      discrepancies between the various conceptions of the borderline patients' psychic
      world and the appropriate therapeutic technique to be applied are also discussed,
      as well as the way the group filters the information and integrates the
      therapeutic thought. It might be said, therefore, that, in the "inpatient" phase
      of the individual psychotherapy, the group of psychotherapists functions, for the
      patient and the treatment, in a synthesizing context, as it provides the
      therapist with a space of integration for his split-off part of self and object
      representations, which the therapist makes use of for his patient.

PMID- 15959673
TI  - A case study of borderline anxiety and the process of analytic transformation.
AB  - Borderline patients present particular treatment problems and require close,
      devoted understanding of their often chaotic and shifting intrapsychic conflicts.
      Many of these patients act out, making it difficult to maintain an analytic
      process. In fact, many terminate early on. When they do stay for longer periods,
      they exhibit particular constellations of defense, anxiety, and conflict. One
      extensive case report is used to examine the overlapping cycles of treatment with
      this population. Frequently, self-destructive acting-out is present in the
      transference and extra-transference. This acting-out is often followed by the
      self-destructive, anti-change attitude of the death instinct. These ways of
      relating to the self and the object are mobilized within the vehicle of
      projective identification and are best understood as primitive defenses against
      core fantasies of loss and persecution. These issues of loss and fear are the
      final and vital phase of treatment with borderline patients, who are often able
      to make major fundamental changes in their internal sphere, but only if patient
      and analyst can tolerate and understand these three levels of intrapsychic
      experience.

PMID- 15959674
TI  - Beyond secondary gain.
AB  - Research suggests that a conscious desire for external illness gain can have
      internal unconscious effects, in that subjective symptoms can be heightened by
      external reward. This mechanism can be explained on the basis of Freud's later
      work, in which he mentions two types of resistance, which resemble each other-
      the need to be punished and the need to be ill. The concept of the need to be ill
      can explain why in modern society, with its established systems of support,
      regulations, and procedures that are conducive to illness behavior, patients who
      consciously strive for external gain can experience strengthening feelings of
      being ill and even deterioration without being aware of this process.

PMID- 15959675
TI  - Immigrant sex: the transport of affection and sensuality across cultures.
AB  - This paper outlines the ways in which an individual's notions of sexuality are
      challenged by immigration. It describes four basic facets of sexuality and the
      ways in which each are rooted in culture. These include (1) the relative
      importance of sexuality in daily life; (2) potential or overt homosexuality; (3)
      marriage-whether based on arrangement or love; and (4) cross-cultural romantic
      and marital relationships. Immigration can stir up conflicts in each of these
      realms and lead to defensive retreat into familiar customs or a counter-phasic
      plunge into new cultural avenues. Ideally, it would lead to a working-through of
      these conflicts and subsequent growth in the immigrant's understanding of his or
      her sexual self.

PMID- 15959676
TI  - Violence as proof of existence: Joyce Carol Oates and the construction of Shelley
      the schizoid.
AB  - Physical violence becomes the unavoidable proof of existence for the character
      Shelley in three works by Joyce Carol Oates: the play "Ontological Proofs of
      Existence," the short story "How I Contemplated the World from the Detroit House
      of Correction and Began My Life Over Again," and the novel Wonderland. Why does
      Shelley need such physical violence as her only proof of existence? What factors
      in the construction of her identity have led to this rather grim choice?
      Psychoanalysis provides a useful tool for understanding Shelley's character, a
      character that comes out to the reader, in the three works, as a schizoid, if not
      indeed schizophrenic. In this paper I argue that the distinction need not be made
      in order to understand the character. In the three works specified here, Shelley
      possesses almost all the characteristics that psychoanalysis tends to attribute
      to the schizoid, and it is by understanding the schizoid in Shelley that we can
      better understand her need for a physical proof of existence.

PMID- 15959677
TI  - Substantial regional variation in substitution rates in the human genome:
      importance of GC content, gene density, and telomere-specific effects.
AB  - This study presents the first global, 1-Mbp-level analysis of patterns of
      nucleotide substitutions along the human lineage. The study is based on the
      analysis of a large amount of repetitive elements deposited into the human genome
      since the mammalian radiation, yielding a number of results that would have been
      difficult to obtain using the more conventional comparative method of analysis.
      This analysis revealed substantial and consistent variability of rates of
      substitution, with the variability ranging up to twofold among different regions.
      The rates of substitutions of C or G nucleotides with A or T nucleotides vary
      much more sharply than the reverse rates, suggesting that much of that variation
      is due to differences in mutation rates rather than in the probabilities of
      fixation of C/G vs. A/T nucleotides across the genome. For all types of
      substitution we observe substantially more hotspots than coldspots, with hotspots
      showing substantial clustering over tens of Mbp's. Our analysis revealed that GC
      content of surrounding sequences is the best predictor of the rates of
      substitution. The pattern of substitution appears very different near telomeres
      compared to the rest of the genome and cannot be explained by the genome-wide
      correlations of the substitution rates with GC content or exon density. The
      telomere pattern of substitution is consistent with natural selection or biased
      gene conversion acting to increase the GC-content of the sequences that are
      within 10-15 Mbp away from the telomere.

PMID- 15959678
TI  - What is the best treatment for stage IV colorectal cancer?

PMID- 15959679
TI  - Simultaneous open rhinoplasty and alar base excision for secondary cases.
AB  - BACKGROUND: Simultaneous open rhinoplasty and alar base excision are a very safe
      procedure for protecting the vascular supply of the nasal dip and the columellar
      skin in primary cases when surgical dissection is performed below the
      musculoaponeurotic layer of the nose. Major arteries of the external nose lie
      above the musculoaponeurotic layer. However, secondary cases may pose increased
      risks to the blood supply of the nasal tip and columella skin because of the
      decreased vascular supply and increased scar tissue from the previous
      rhinoplasty. We studied our secondary cases of simultaneous open rhinoplasty and
      alar base excision, to assess the real risk for necrosis of the nasal tip and
      columellar skin. METHODS: A total of 12 secondary patients (6 men and 6 women)
      underwent simultaneous open rhinoplasty and alar base excision in the past 3
      years. Their average age was 27 years (range, 21-35 years). The average follow-up
      period was 15 months (range, 1-35 moths). A modified grading system, originally
      described by Bafaqeeh and Al-Qattan, was used for assessment of the blood supply
      in the nasal tip and the columellar skin. RESULTS: Satisfactory results were
      obtained for our patients, with the exception of one case. Grade 3 vascular
      compromise to the nasal tip and the columella was observed in one case, but the
      patient healed well with wound care treatment. CONCLUSION: Simultaneous alar base
      excision and open rhinoplasty can be performed safely in secondary cases. However
      some surgical maneuvers such as subcutaneous pocket preparation for the tip graft
      in closed rhinoplasty and subdermal defatting in the first rhinoplasty as well as
      previous scarring on the nasal lobule can disrupt the vascular supply of the
      nasal tip and columella skin. Under these conditions, alar base excision should
      be deferred and then performed as an isolated excision procedure.

PMID- 15959682
TI  - Cutis marmorata resemblance after liposuction.
AB  - Liposuction is a safe method for the treatment of lipodystrophy. It gives good
      results in relation to body contours, especially when the superficial and deep
      layers of the superficial fascia are aspirated. The authors present clinical
      cases of female patients who underwent liposuction of the abdomen, flanks, and
      back in which superficial and deep liposuction was used. In the immediate
      postoperative period, these patients presented a skin pattern of marbled
      appearance, involving rosy-purplish stains intermingled with other whitish stains
      on the skin in the areas subjected to surgery and resembling the cutis marmorata
      described in the literature. Even 1 year after the operation, the stains had not
      receded. The literature mentions cases of cutaneous necrosis provoked by a
      temperature increase induced by liposuction cannulas. This trauma said to be the
      determining factor for local lesions of the subdermal plexus. However, no cases
      involving lesions of this plexus attributable to mechanical trauma from cannulas
      are cited. According to several authors, it is important during superficial
      liposuction to maintain a strip about 1 cm thick under the deep dermis for the
      preservation of the arterial plexus of the skin. This would avoid the formation
      of a skin pattern resembling cutis marmorata.

PMID- 15959683
TI  - Augmentation rhinoplasty with a combination of triple cartilage grafts for
      secondary rhinoplasty in a middle-aged population.
AB  - Because of physiologic changes with advancing age as well as previously
      traumatized and then healed tissues, secondary rhinoplasty for a middle-aged
      patient is a challenging procedure. Depending on both factors, changes in the
      midvault can cause a functional airway disorder, and the nose also may need a
      complete correction for cosmetic purposes. To achieve aesthetic and functional
      outcomes, augmentation rhinoplasty using a combination of triple cartilage
      grafts, namely, spreader, columellar, and dorsal onlays, was performed for 12
      patients. Sufficient nasal airways with satisfactory appearance were achieved for
      11 of 12 patients. Only one patient had improved but still insufficient nasal
      function with a good aesthetic result. Augmentation rhinoplasty using a
      combination of triple cartilage grafts for middle-aged patients could be
      considered an effective procedure for improving the patient's nasal airway and
      appearance.

PMID- 15959684
TI  - Radiologic and histologic assessment of diced cartilage grafts for cranial bone
      defects of rabbits: an experimental study.
AB  - This study was performed to experimentally evaluate the viability and coverage of
      diced cartilage grafts for cranial defects. Biparietal bone defects were prepared
      in each of 20 rabbits. Otogenous bone grafts were fixed to one side, whereas
      cartilage grafts taken from the right ear, diced, and wrapped with oxidized
      regenerated cellulose (Surgicel) were placed on other side. Parenchymal
      impression, contour, and ossification of all grafts in the 16 rabbits surviving
      after 8 weeks were evaluated with computed tomography and magnetic resonance
      imaging. The existence of ossification was examined pathologically. Parenchymal
      impression was significantly more frequent in bone grafts than in cartilage
      grafts (p < 0.05). This difference probably is attributable to the application
      technique. There was no significant radiographic difference in other parameters
      between the two groups. No significant difference in ossification was found. In
      conclusion, ossification was seen radiologically and pathologically in diced
      cartilage grafts. Because of autogenicity, ease of shaping, absence of
      postoperative warping, reduced resorption rates, and inherent viability and
      ossification properties, the authors suggest that diced cartilage grafts may be
      an alternative material for cranial defects, especially for frontal cranial
      reconstruction in which deformities may cause aesthetic and functional
      disabilities. The authors believe that further long-term studies also are needed.

PMID- 15959685
TI  - Blepharoplasty and otoplasty: comparative sedation with remifentanil,propofol,
      and midazolam.
AB  - Three different methods of sedation or sedoanalgesia using remifentanil,
      Propofol, or midazolam to increase intra- and postoperative comfort and to reduce
      neuroendocrine stress in patients who had undergone typical ambulatory cosmetic
      surgery under local anesthesia were studied. A sample of 90 patients who
      underwent upper and lower eyelid blepharoplasty to correct baggy eyelids or
      otoplasty to correct protruding ears was selected according to standard criteria
      for the study. Remifentanil provided the best tolerability profile and the most
      effective perioperative pain control among the substances studied, demonstrating
      it to be a valid drug for modern sedoanalgesia aimed at increasing the well-being
      of patients undergoing ambulatory cosmetic surgery.

PMID- 15959686
TI  - Making concave faces convex.
AB  - Inadequate projection of the midface skeleton results in midface concavity.
      Patients with this skeletal morphology tend to have prominent eyes and noses.
      Lack of skeletal support for the midface soft tissue envelope predisposes to
      premature cheek descent, resulting in palpebral fissure distortion and lower lid
      "bags," an appearance of early aging. Concave midfaces can be made convex with
      two basic maneuvers performed through intraoral and periorbital incisions.
      Midface skeletal projection can be increased by augmenting the facial skeleton
      with alloplastic implants. Multiple implants are required to replicate the
      complex curvature of the midface skeleton and to avoid impingement on the
      infraorbital nerve. Subperiosteal elevation of the midface soft tissues and
      repositioning provides cheek fullness and narrows the palpebral fissure while
      masking eyelid "bags." The resultant midface concavity makes the eyes and nose
      appear less prominent. This procedure has been a safe and effective treatment for
      14 patients treated over a 4-year period.

PMID- 15959687
TI  - Familial severe gigantomastia and reduction with the free nipple graft vertical
      mammoplasty technique: report of two cases.
AB  - BACKGROUND: : Gigantomastia, characterized by massive breast enlargement during
      adolescence or pregnancy, is thought to be caused by an abnormal and excessive
      end organ response to a normal hormonal milieu. The amputation technique with the
      free nipple-areola graft is the mainstay for severe macromastia, but it has been
      criticized because it results in a flattened, nonaesthetic breast with poor
      projection. This report presents two sisters with unusual, excessive breast
      enlargement. METHODS: : The measured distance from the sternal notch to the
      nipple was 50 cm for the first case and 55 cm for the second case. The free
      nipple graft transplantation based on the vertical mammoplasty technique was
      used, and an average of 4,200 g of breast tissue per breast was removed. To
      increase breast projection, superior dermoglandular flaps were used RESULTS: :
      The follow-up period was 24 months. The patients had long-lasting, pronounced
      breast mound projection, and the level of satisfaction for both cases was very
      high. CONCLUSION: The ideal geometric structure of the breast is rather conical,
      and the authors believe that reshaping the breast tissue in a vertical plane
      using the vertical mammoplasty technique may be more effective in the long term
      and may provide better projection.

PMID- 15959688
TI  - Mersiline mesh in premaxillary augmentation.
AB  - Premaxillary retrusion may distort the aesthetic appearance of the columella,
      lip, and nasal tip. This defect is characteristically seen in, but not limited
      to, patients with cleft lip nasal deformity. This study investigated 60 patients
      presenting with premaxillary deficiencies in which Mersiline mesh was used to
      augment the premaxilla. All the cases had surgery using the external rhinoplasty
      technique. Two methods of augmentation with Mersiline mesh were used: the
      Mersiline roll technique, for the cases with central symmetric deficiencies, and
      the Mersiline packing technique, for the cases with asymmetric deficiencies.
      Premaxillary augmentation with Mersiline mesh proved to be simple technically,
      easy to perform, and not associated with any complications. Periodic follow-up
      evaluation for a mean period of 32 months (range, 12-98 months) showed that an
      adequate degree of premaxillary augmentation was maintained with no clinically
      detectable resorption of the mesh implant.

PMID- 15959689
TI  - Self-perception and self-esteem of patients seeking cosmetic surgery.
AB  - Cosmetic surgery represents a particular application of plastic surgery, in which
      the operative competence of the discipline is focused not on the correction of
      pathological disorders, but on the correction of some morphologic traits not
      accepted by the patients, or not adherent with the aesthetic canons of the time,
      although they are absolutely compatible with the norm. As a consequence, cosmetic
      surgery recognizes subjective indications. According to a particular literature
      on the subject, patients seeking these interventions would live a dualism between
      (their own) body image and inner self-image. Very psychotic case histories would
      come out of this. A base psychological approach adopted by the surgeon, competent
      both in the surgical and the psychological level, is absolutely needed. In this
      study, the psychological features of patients seeking cosmetic surgery were
      explored in an attempt to define common profiles or prevalent characteristics,
      and to isolate major psychiatric disorders. Patient self-esteem and physical self
      perception also were investigated.

PMID- 15959690
TI  - Deskinning versus deepithelialization for inferior pedicle reduction mammoplasty:
      a prospective comparative analysis.
AB  - BACKGROUND: Deepithelialization is time consuming, but has been performed
      traditionally in reduction mammaplasty to ensure a better blood supply to the
      transposed nipple-areolar complex. METHODS: For this study, 18 patients were
      recruited, and each patient served as an individual control by undergoing both
      deskinning and deepithelialization of the contralateral breast. The patient's
      age, body mass index, specimen weight, complications, and subjective cosmetic
      assessment were recorded. RESULTS: The mean age was 42 years, and the mean body
      mass index was 27.94 respectively. There were no differences recorded in terms of
      complications or patient perceived cosmetic outcomes. The only statistical
      difference involved the times required for deepithelialization (15.5 min) and
      deskinning (6 min). Deskinning thus saved approximately 9 min. CONCLUSIONS:
      Deskinning is as effective as deepithelialization and is significantly more
      expedient, with no added risk to the patient.

PMID- 15959691
TI  - Drains in aesthetic surgery: should they be radio-opaque or not?

PMID- 15959692
TI  - Misconceptions about mandible reduction procedures.
AB  - Mandible reduction procedures are currently very popular in Asian countries. But
      many misconceptions or differences in concepts about these procedures still
      exist, mainly because of preconceived ideas and restriction in communication. The
      author reviewed articles and found some misconceptions about these procedures.
      Also, the author added some opinions regarding new ideas about these procedures
      (i.e., minimal incision technique and botulinum toxin), as well as logical
      backgrounds of associated concepts. The intraoral approach is the safest and most
      effective procedure. The sagittal split ostectomy is the most important procedure
      for mandible reduction.

PMID- 15959693
TI  - The feasibility of sentinel lymph node detection in patients with previous
      transaxillary implant breast augmentation: preliminary results.
AB  - BACKGROUND: Transaxillary breast augmentation has gained popularity because of
      the good aesthetic results and scar placement in a less visible position. As
      breast-augmented patients age, an increasing number of breast cancer cases can be
      expected. Sentinel lymph node detection (SLND) is a well-established technique in
      breast cancer. To date, no information is available regarding the feasibility of
      SLND for patients with previous transaxillary implants. METHODS: A 28-year-old
      women with bilateral breast hypoplasia underwent a bilateral breast augmentation
      by the transaxillary approach. One week earlier, SLND was accomplished through
      two periareolar injections of 0.1 mCi 99m-technetium-labeled fitate and
      lymphoscintigraphy. A 3.5-cm-long axillary incision was performed, and the
      dissection continued through the subfascial plane to create the implant's pocket.
      A silicone gel implant (215 g round, low-profile, textured Silimed) was inserted.
      RESULTS: A satisfactory aesthetic result was obtained. Two postoperative
      lymphoscintigraphies were performed (15 days and 7 months after surgery) with
      satisfactory SLND. No complication was noted. CONCLUSION: The initial data show
      that SLND in the setting of prior breast implant augmentation through the
      transaxillary approach is feasible. Additional prospective studies and larger
      clinical series are necessary to analyze the accuracy of SLND for patients with
      previous breast implants.

PMID- 15959694
TI  - Successful endovascular repair of ruptured abdominal aortic aneurysm in a renal
      transplant recipient.
AB  - A renal transplant recipient presented in the early post-transplantation period
      with rupture of an abdominal aortic aneurysm. The high mortality rate of the
      surgical repair of ruptured aneurysm in addition to the concern of preserving the
      renal graft prompted us to seek alternative approaches, such as repairing the
      aneurysm by means of endovascular techniques. The ruptured aneurysm was confirmed
      by performing computed tomography and digital angiography and thereafter was
      successfully repaired by endovascular stenting technique (Talent stent-graft),
      which seems to be a safe and effective method of preserving a renal graft.

PMID- 15959695
TI  - Transarterial embolization of common hepatic artery pseudoaneurysm secondary to
      aortic dissection.

PMID- 15959696
TI  - Symptomatic internal carotid artery dissecting pseudoaneurysm: endovascular
      treatment by stent-graft.
AB  - Dissecting pseudoaneurysm of the extracranial portion of the internal carotid
      artery (ICA) is a usually benign complication of spontaneous ICA dissection. We
      report a case in which pseudoaneurysm volume enlarged progressively and new
      clinical symptoms developed 9 months following disease onset. Placement of a
      coronary stent-graft resulted in immediate complete resolution of clinical
      symptoms and radiologic restoration of normal flow.

PMID- 15959697
TI  - Biomaterials used in injectable implants (liquid embolics) for percutaneous
      filling of vascular spaces.
AB  - The biomaterials currently used in injectable implants (liquid embolics) for
      minimally invasive image-guided treatment of vascular lesions undergo, once
      injected in situ, a phase transition based on a variety of physicochemical
      principles. The mechanisms leading to the formation of a solid implant include
      polymerization, precipitation and cross-linking through ionic or thermal process.
      The biomaterial characteristics have to meet the requirements of a variety of
      treatment conditions. The viscosity of the liquid is adapted to the access
      instrument, which can range from 0.2 mm to 3 mm in diameter and from a few
      centimeters up to 200 cm in length. Once such liquid embolics reach the vascular
      space, they are designed to become occlusive by inducing thrombosis or directly
      blocking the lesion when hardening of the embolics occurs. The safe delivery of
      such implants critically depends on their visibility and their hardening
      mechanism. Once delivered, the safety and effectiveness issues are related to
      implant functions such as biocompatibility, biodegradability or biomechanical
      properties. We review here the available and the experimental products with
      respect to the nature of the polymer, the mechanism of gel cast formation and the
      key characteristics that govern the choice of effective injectable implants.

PMID- 15959698
TI  - Bronchial artery embolization for life-threatening hemoptysis using tris-acryl
      microspheres: short-term result.
AB  - A prospective study of 70 patients with life-threatening hemoptysis who had
      bronchial and systemic artery embolization with tris-acryl linked microspheres
      was performed over 15 months. The procedure was technically successful in 90% of
      patients and at 24 hr after the procedure (87%). Recurrent hemoptysis occurred in
      13% of patients within the first week. Chest pain was experienced following
      embolization in 7% of patients. The mortality was 10% due to the inclusion of
      patients with pulmonary metastases. Bronchial artery embolization using
      microspheres is an effective and well-tolerated treatment for patients with life
      threatening hemoptysis who are not surgical candidates.

PMID- 15959699
TI  - Single-pass percutaneous liver biopsy for diffuse liver disease using an
      automated device: experience in 154 procedures.
AB  - PURPOSE: To describe our experience with ultrasound (US)-guided percutaneous
      liver biopsies using the INRAD 18 G Express core needle biopsy system. METHODS:
      One hundred and fifty-four consecutive percutaneous core liver biopsy procedures
      were performed in 153 men in a single institution over 37 months. The medical
      charts, pathology reports, and radiology files were retrospectively reviewed. The
      number of needle passes, type of guidance, change in hematocrit level, and
      adequacy of specimens for histologic analysis were evaluated. RESULTS: All
      biopsies were performed for histologic staging of chronic liver diseases. The
      majority of patients had hepatitis C (134/153, 90.2%). All patients were
      discharged to home after 4 hr of post-procedural observation. In 145 of 154 (94%)
      biopsies, a single needle pass was sufficient for diagnosis. US guidance was
      utilized in all but one of the procedures (153/154, 99.4%). The mean hematocrit
      decrease was 1.2% (44.1--42.9%). Pain requiring narcotic analgesia, the most
      frequent complication, occurred in 28 of 154 procedures (18.2%). No major
      complications occurred. The specimens were diagnostic in 152 of 154 procedures
      (98.7%). CONCLUSIONS: Single-pass percutaneous US-guided liver biopsy with the
      INRAD 18 G Express core needle biopsy system is safe and provides definitive
      pathologic diagnosis of chronic liver disease. It can be performed on an
      outpatient basis. Routine post-biopsy monitoring of hematocrit level in stable,
      asymptomatic patients is probably not warranted.

PMID- 15959700
TI  - Fatal intraventricular hemorrhage after the extracranial carotid artery
      angioplasty and stent placement.
AB  - We report on a 72-year-old female with an unusual intracranial bleeding
      complication after an extracranial carotid artery stenting procedure performed
      for a tight left ICA stenosis associated with contralateral carotid occlusion.
      Two hours after the procedure, the initial signs of intracranial bleeding
      appeared that led to the patient's demise 5 days later. A brain CT showed and
      autopsy proved massive intraventricular bleeding. To our knowledge, our case is
      only the second report of isolated reperfusion intraventricular hemorrhage post
      CAS.

PMID- 15959701
TI  - Multislice spiral computed tomography of the heart: technique, current
      applications, and perspective.
AB  - Multislice spiral computed tomography (MSCT) is a rapidly evolving, noninvasive
      technique for cardiac imaging. Knowledge of the principle of electrocardiogram
      gated MSCT and its limitations in clinical routine are needed to optimize image
      quality. Therefore, the basic technical principle including essentials of image
      postprocessing is described. Cardiac MSCT imaging was initially focused on
      coronary calcium scoring, MSCT coronary angiography, and analysis of left
      ventricular function. Recent studies also evaluated the ability of cardiac MSCT
      to visualize myocardial infarction and assess valvular morphology. In combination
      with experimental approaches toward the assessment of aortic valve function and
      myocardial viability, cardiac MSCT holds the potential for a comprehensive
      examination of the heart using one single examination technique.

PMID- 15959702
TI  - Kinetics of degradation of hydrocarbons in the contaminated soil layer.
AB  - This work presents kinetic parameters of the removal of hydrocarbons in the
      course of bioremediation of the soil contaminated with crude and oil derivatives,
      with special emphasis paid to polycyclic aromatic hydrocarbons. Bioremediation
      was carried out on a laboratory scale, with continuous and discontinuous
      recirculation of water through the soil column inoculated with the adapted
      bacterial population. Biodegradation of hydrocarbons can be described by the
      following equation--ln C = ln C0- kt--which is most often used in the literature
      to describe degradation of hydrocarbons, and by the equation--ln C = ln C0- kt0.5
      -which is determined on the basis of experimental data (except for pyrene and
      chrysene, for which a linear equation was used). A comparison of the two models
      showed a significant difference in the calculated remediation times, indicating
      that it is not realistic to expect a simple kinetic model to provide precise and
      accurate descriptions of concentrations during different seasons and in different
      environments. The results indicated that once contaminated with hydrocarbons,
      soil can be slowly brought to the previous state provided that no new
      contamination has occurred.

PMID- 15959703
TI  - Chlorinated hydrocarbon contaminants and stable isotope ratios in pelagic
      seabirds from the North Pacific Ocean.
AB  - Organochlorine pesticides, polychlorinated biphenyls (PCBs), and stable isotopes
      of nitrogen (delta15N) and carbon (delta13C) were determined in livers of eight
      seabird species (Diomedea immutabilis, D. nigripes, Fulmarus glacialis, Puffinus
      bulleri, P. carneipes, P. griseus, P. tenuirostris, and Fratercula corniculata)
      collected opportunistically from an experimental fishery in the North Pacific
      Ocean. Concentrations of P, P'-DDE were found in all samples but were highly
      variable among species, ranging over >2 orders of magnitude from 1.23 mg/kg (wet
      weight) in D. nigripes to 0.008 mg/kg in P. tenuirostris, whereas total PCBs
      ranged from 1.14 to 0.020 mg/kg in those same two species. Residues of
      hexachlorobenzene, trans-nonachlor, photo-mirex, mirex, beta
      hexachlorocyclohexane, oxychlordane, and heptachlor expoxide were quantified at
      lower concentrations in all samples. There were significant positive regressions
      of lipid-normalized concentrations of DDE (r2 = 0.526), total PCBs (r2 = 0.566),
      CB-153 (r2 = 0.565), and mirex (r2 = 0.586) on the hepatic delta15N signature,
      indicating that trophic level accounted for approximately 50% of the variability
      in those contaminants among species. In some species, e.g., P. bulleri,
      concentrations were lower than expected based on delta15N, which was attributed
      to a dietary switch before sampling and therefore lack of concordance in the time
      scales integrated by hepatic chlorinated hydrocarbon concentrations compared with
      delta15N.

PMID- 15959704
TI  - Fate of triclosan and triclosan-methyl in sewage treatment plants and surface
      waters.
AB  - The fate of triclosan in diverse stages of two sewage treatment processes has
      been determined. The elimination process differed considerably depending on the
      technology applied in the respective sewage treatment plant (STP). The plant
      operating with a two-stage biologic (activated sludge) process removed triclosan
      more efficiently than the STP with a combination of physical and activated sludge
      process. The treatment in the aeration basin was the dominant elimination
      mechanism, whereas the final biologic filter was not very effective. The
      elimination rates for triclosan were 87% and 95%, respectively. These data were
      compared with emissions of a multitude of STPs in the river Ruhr catchment area
      as well as triclosan and its known transformation product, triclosan-methyl, in
      the river. The concentrations of both compounds were between <3 and 10 ng/L in
      true surface-water samples for triclosan and between 0.3 and 10 ng/L for
      triclosan-methyl. The STP effluents held higher concentrations (10 to 600 ng/L
      triclosan). The ratio of triclosan to triclosan-methyl did not change
      significantly within the longitudinal profile of the river, but diverse STPs
      discharging to the river exhibited individual triclosan-to-triclosan-methyl
      ratios. From the riverine concentration data, in-river elimination rates and half
      life were estimated.

PMID- 15959705
TI  - The temporal and spatial variations of acid aerosols in the geothermal area of
      metropolitan Taipei, Taiwan.
AB  - This study involved sampling over 1 year of data on exposure to acid aerosols in
      the geothermal area of metropolitan Taipei. The temporal and spatial variations
      of the concentrations of acid aerosols were assessed by sampling at three sites:
      A, B, and C. Results indicate that the SO2 concentrations lead the concentrations
      of other acid aerosols at site C because two active fumaroles surround this site.
      The mean SO2 concentrations at sites A, B, and C were 2.4, 2.4, and 6.2 ppb.
      Previous studies have found that H2S levels were highest at site C. However, the
      SO4(-2) and H+ concentrations among the three sites were similar. The mean
      aerosol SO4(-2) concentrations were 7.0, 5.7, and 5.7 microg m(-3) at sites A, B,
      and C, respectively; their H+ concentrations were 5.5, 4.2, and 5.4 nmol m(-3).
      No seasonal variations are observed for most of the acid aerosols in the
      geothermal area except that the types of hot spring affect the SO4(-2)
      concentration nearby. The different seasonal fluctuation among the sites reflect
      the determinant of SO4(-2) emission from different geothermal sources. Sulfur
      rich aerosols and some SO2 emitted from geothermal sources are obvious. The
      predominance of nitrogen-containing gases (sum of NO2 + HNO2 + HNO3) over SO2
      indicates the importance of the anthropogenic origin of emissions. The effect of
      multiple exposures to sulfur-rich aerosol (including H2S, SO2, and SO4(-2)), H+,
      and nitrogen-containing aerosols on the health of nearby residents warrants
      concern.

PMID- 15959706
TI  - Lead concentrations in ruffed grouse, rock ptarmigan, and willow ptarmigan in
      Quebec.
AB  - Between 1996 and 1998, ruffed grouse, spruce grouse, willow ptarmigan, and rock
      ptarmigan harvested by hunters in Quebec were examined for lead contamination. On
      examination of the gizzards of these birds, lead shot was found only in ruffed
      grouse (1.2%). The probability of ingestion of lead shot by grouse and ptarmigans
      is low. Analyses of the lead concentrations in the wing bones of grouse and
      ptarmigans and in the muscle tissue of ptarmigans were conducted. Although
      differences were observed between individuals based on age and sex, the mean
      concentrations measured were in the range of those that occur naturally at
      background levels (<6 microg/g dw). Lead concentrations in muscle tissue were
      low, often at the limit of detection. However, the few high concentrations
      detected were probably related to a lead pellet or bullet fragment. Based on an
      analysis of the health risk associated with consumption of ptarmigan muscle, we
      conclude that the use of lead ammunition for hunting gallinaceous birds may pose
      an unnecessary risk of lead poisoning because of the possible ingestion of lead
      shot, bullets, fragments or embedded shot.

PMID- 15959707
TI  - Laparoscopic hand-assisted versus open transhiatal esophagectomy: a case-control
      study.
AB  - BACKGROUND: This case-control study evaluated and compared the outcomes of
      laparoscopically assisted (LTE) and open transhiatal esophagectomy (OTE).
      METHODS: In this study, 17 patients who underwent LTE during this period August
      1999 through June 2003 were compared with 14 matched control patients who
      underwent OTE during this period December 1989 through September 2001. The groups
      had stage I esophageal cancer or lesser disease at the preoperative evaluation.
      Patients with prior upper abdominal or thoracic surgery were excluded. RESULTS:
      There was no significant difference between the groups with respect to age, body
      mass index, American Society of Anesthesiology (ASA) classification, or operating
      time. The estimated blood loss was 331 (+/- 220) ml for LTE and 542 (+/- 212) ml
      for OTE (p = 0.01). The hospital stay was 9.1 (+/- 3.2) days for LTE and 11.6 (+/
      2.9) days for OTE (p = 0.04). Comparing only the last six LTE with the OTE, the
      operating time was 311 (+/- 31) min for LTE and 388 (+/- 14) min for OTE (p =
      0.02). CONCLUSIONS: The findings showed shorter operative time, less blood loss,
      and a shorter hospital stay with LTE than with OTE.

PMID- 15959708
TI  - Colonoscopy vs CT colonography to screen for colorectal neoplasia in average-risk
      patients.

PMID- 15959710
TI  - Laparoscopic management of acute small bowel obstruction.
AB  - BACKGROUND: As minimally invasive surgery gains ground, it is entering realms
      previously considered to be relative contraindications for laparoscopy. We
      reviewed our experience with the laparoscopic approach to the management of small
      bowel obstruction (SBO). METHODS: From December 1997 to November 2002, 65
      patients underwent laparoscopic treatment for SBO. The operating surgeon
      attempted to identify a transitional point between distended and collapsed bowel
      and then address the obstruction at that point. RESULTS: Postoperative adhesions
      were the cause of the obstruction in 44 patients. Tumor was identified in five
      cases, hernia in four, bezoar in three, intussusception in three, acute
      appendicitis and pseudoobstruction in two cases each, and terminal ileitis in one
      case. The diagnostic accuracy of laparoscopy was 96.9%. Thirty-four patients
      (52%) were treated by laparoscopy alone. Thirteen patients (20%) required a small
      target incision for segmental resection. Eighteen operations were converted to
      formal laparotomy. The mean laparoscopy time was 40 min (range, 25-160). Patients
      resumed oral intake in 1-3 days. The complication rate was 6.4%. There were two
      deaths, but none related to laparoscopy. The mean hospital stay was 4.2 days.
      CONCLUSIONS: Laparoscopy is a useful minimally invasive technique for the
      management of acute SBO. It is an excellent diagnostic tool and, in most cases, a
      therapeutic surgical approach in patients with SBO. However, a significant number
      of patients will require conversion.

PMID- 15959711
TI  - Laparoscopic resection of splenic artery aneurysms.
AB  - BACKGROUND: Laparoscopic techniques used to manage asymptomatic splenic artery
      aneurysms have been reported infrequently. METHODS: A laparoscopic splenic artery
      aneurysm resection was attempted for six consecutive patients. RESULTS: One
      patient underwent conversion to laparotomy because of a tear in the splenic vein.
      Among the five successful laparoscopic splenic artery aneurysm resections, the
      mean estimated blood loss was 37 +/- 12.6 ml, the mean operative time was 187.6
      +/- 79.2 min, and the mean postoperative length of hospital stay was 1.8 +/- 1.3
      days. The mean time to a clear liquid diet was 5.3 +/- 0.5 h, and the mean time
      to a regular diet was 1 +/- 0 day. The mean duration of narcotic analgesic use
      was 5.4 +/- 1.5 days, and the mean time to resumption of regular activities was
      12.7 +/- 1.6 days. CONCLUSIONS: These cases illustrate the benefit of a
      laparoscopic approach with brief hospitalizations, early resumption of diet and
      regular activity, and minimal use of postoperative narcotic analgesics.

PMID- 15959712
TI  - Laparoscopic Nissen fundoplication in patients with nonerosive reflux disease.
      Long-term quality-of-life assessment and surgical outcome.
AB  - BACKGROUND: It is known that laparoscopic antireflux surgery (LARS) can achieve
      an excellent surgical outcome including quality of life improvement in patients
      with erosive gastroesophageal reflux disease (GERD; EGD-positive). Less is known
      about the long-term surgical outcome in GERD patients who have no evidence of
      esophagitis (EGD-negative) before surgery. The aim of this study was to evaluate
      the surgical outcome in a well-selected group of EGD-negative patients compared
      to that of EGD-positive patients. METHODS: From a large sample of more than 500
      patients who underwent LARS, 89 EGD-negative patients (mean age, 51 +/- 6 years;
      56 males) were treated surgically because of persistent reflux-related symptoms
      despite medical therapy. In all cases, preoperative 24-h pH monitoring showed
      pathological values. To perform a comparative analysis, a matched sample of EGD
      positive patients (mean age, 54 +/- 10 years; 58 males) was selected from the
      database. Surgical outcome included for all patients objective data (e.g.,
      manometry and pH data and endoscopy), quality of life evaluation
      [Gastrointestinal Quality of Life Index (GIQLI)] symptom evaluation, as well as
      patients' satisfaction with surgery. The data of a complete 5-year follow-up are
      available. RESULTS: There were no significant differences in symptomatic
      improvement, percentage of persistent surgical side-effects, or objective
      parameters. In general, patients' satisfaction with surgery was comparable in
      both groups: 95% rated long-term outcome as excellent or good and would undergo
      surgical treatment again if necessary, respectively. Quality of life improvement
      was significantly better (p < 0.05) in the EGD-negative group because of the fact
      that GIQLI was more impaired before surgery (preoperative GIQLI, 81.7 +/- 11.6
      points/EGD-negative vs 93.8 +/- 10.3 points/EGD-positive). Five years after
      surgery, GIQLI in both groups (121.2 +/- 8.5 for EGD-negative vs 120.9 +/- 7.3
      for EGD-positive) showed comparable values to healthy controls (122.6 +/- 8.5).
      CONCLUSION: We suggest that LARS is an excellent treatment option for well
      selected patients with persistent GERD-related symptoms who have no endoscopic
      evidence of esophagitis.

PMID- 15959713
TI  - Laparoscopic-assisted jejunostomy: an effective procedure for the treatment of
      neurologically impaired children with feeding problems and gastroesophageal
      reflux.
AB  - BACKGROUND: Feeding difficulties and gastroesophageal reflux (GER) are major
      problems in severely neurologically impaired children. Many patients are managed
      with a simple gastrostomy, with or without fundoplication. Unfortunately,
      fundoplication and gastrostomy are not devoid of complications, indicating the
      need for other options in the management of these patients. METHODS: Since
      January 2002, seven patients (age range, 5-14 years) have been treated by
      creating a jejunostomy with the laparoscopic-assisted procedure. The procedure
      was performed using two 10-mm trocars. The technique consists of identifying the
      first jejunal loop, grasping it 20-30 cm away from the Treitz ligament with
      fenestrated atraumatic forceps, and exteriorizing it to the trocar orifice under
      visual guide. The jejunostomy was created outside the abdominal cavity during
      open surgery. At the end of the jejunostomy, the correct positions of the
      intestinal loop and feeding tube were evaluated via laparoscopy. RESULTS: Surgery
      lasted 40 min on average, the laparoscopic portion only 5 min. There were no
      perioperative complications; hospital stay was 3 or 4 days for all patients. At
      the longest follow-up (18 months), all patients had experienced a significant
      weight gain, with a high level of parental satisfaction. One patient died 1 year
      after the procedure of unknown causes. All the others are well, without
      complications or problems, and their parents are extremely satisfied with the
      improved quality of life of their children. CONCLUSIONS: Laparoscopic-assisted
      jejunostomy is a safe and effective procedure to adopt in neurologically impaired
      children with feeding problems and GER. This procedure solves these patients'
      feeding problems even if the reflux is not completely eliminated. We advocate the
      use of this procedure in neurologically impaired patients with feeding problems
      and reflux due to its overall practicability and because there is minimal
      surgical trauma. This technique is extremely safe because the surgeon is able to
      verify, at the end of procedure, the status of the jejunostomy from outside and
      inside the abdominal cavity. The improvement in the quality of life of these
      children after the jejunostomy seems to be the major advantage of this procedure.

PMID- 15959714
TI  - Reappraisal of percutaneous transhepatic cholangioscopic lithotomy for primary
      hepatolithiasis.
AB  - BACKGROUND: A review of the literature pertaining to percutaneous transhepatic
      cholangioscopic lithotomy (PTCSL) showed that more than 50% of reported patients
      had undergone earlier biliary surgery. METHODS: A retrospective study
      investigated 74 patients undergoing initial PTCSL for hepatolithiasis who had
      undergone no prior biliary surgery or manipulation. The patients were followed
      for 1 to 23 years after PTCSL for effective evaluation of the procedure outcome.
      RESULTS: Complete clearance of hepatolithiasis was achieved for 61 (82%)
      patients. The incomplete clearance rate was higher for patients with intrahepatic
      duct stricture (11/37 [30%] vs 2/37 [5%]; p < 0.05), although it showed no
      relation to the actual lobar distribution of hepatolithiasis (left: 7/41 [17%] vs
      right: 2/11 [18%] vs bilateral: 4/22 [18%]; p < 0.05). The recurrence rate for
      hepatolithiasis also was higher for patients with intrahepatic duct stricture
      (18/26 [69%] vs 13/35 [37%]; p < 0.05), but the recurrence rate showed no
      relation to the lobar distribution of hepatolithiasis (left: 18/34 [53%] vs
      right: 4/9 [44%] vs bilateral: 9/18 [50%] p > 0.05) or the presence of
      gallbladder stones (5/12 [42%] vs 26/49 [53%]; p > 0.05). Patients showing the
      coexistence of retained or recurrent hepatolithiasis demonstrated a higher
      incidence of recurrent cholangitis (57% [13/23] vs 14% [7/51]; p < 0.01) or
      cholangiocarcinoma (17% [4/23]) vs 0% [0/51]; p < 0.01). CONCLUSIONS: The
      findings show that PTCSL is effective for treating primary hepatolithiasis, and
      that complete stone clearance is mandatory to diminish the sequelae of
      hepatolithiasis. Intrahepatic duct stricture was the main factor contributing to
      incomplete clearance and stone recurrence.

PMID- 15959715
TI  - Management of asymptomatic cholelithiasis for patients awaiting renal
      transplantation.
AB  - BACKGROUND: There is no consensus regarding the most appropriate management of
      asymptomatic cholelithiasis in patients awaiting renal transplantation.
      Cholecystectomy is considered before renal transplantation because of potential
      worsened complications from cholelithiasis with posttransplantation
      immunosuppression. This study reviewed the outcomes for operative and
      nonoperative management of asymptomatic cholelithiasis in patients awaiting renal
      transplantation. METHODS: A retrospective chart review of all patients who
      received renal transplant at the authors' institution during the period 1994 to
      2000 was completed. All patients underwent pretransplantation abdominal
      ultrasound. RESULTS: Of the 411 patients receiving renal transplants (242 men and
      169 women with a mean age of 45.7 years), 32 had cholelithiasis at the
      pretransplantation workup (7.8%), and 35 had gallbladder abnormalities (8.5%):
      polyps, thickened wall, sludge, bile duct dilation. Before transplantation, 12 of
      the 32 patients (38%) with cholelithiasis underwent uncomplicated
      cholecystectomy. None of the remaining 19 patients with cholelithiasis required
      cholecystectomy after renal transplantation (mean follow-up period 6.2 years). Of
      the 35 patients with gallbladder abnormalities, 2 required post transplantation
      elective cholecystectomy. CONCLUSIONS: No evidence was found for increased
      morbidity related to cholelithiasis or gallbladder abnormalities after renal
      transplantation. As in the general population, the risks associated with
      asymptomatic cholelithiasis do not appear to warrant prophylactic cholecystectomy
      for patients awaiting renal transplantation.

PMID- 15959717
TI  - Continent ileostomy: current experience.
AB  - PURPOSE: This study was designed to review our recent experience with continent
      ileostomies and evaluate patient outcomes. METHODS: Retrospective chart reviews
      and phone interviews of patients who underwent a continent ileostomy operation
      from 1993 to 2003 at the Ochsner Clinic Foundation were performed. RESULTS:
      Twenty-four patients (19 females; age range, 22-73 years) had construction of
      continent ileostomies (modified Kock pouch). There were no intraoperative
      mortalities or stoma-related deaths. The mean operating room time for primary
      construction was 3.9 +/- 0.57 hours with a mean length of stay of 7 +/- 2 days.
      The average follow-up period was 66 (range, 6-134) months. The most common
      underlying indication for the construction of a continent ileostomy was
      ulcerative colitis (71 percent). Thirteen patients had a continent ileostomy
      created for conversion of a Brooke ileostomy and seven for a failed ileoanal
      pouch. Other indications included colonic inertia and incontinence in three
      patients and one patient who had failed multiple operations for Hirschsprung's
      disease. A total of 28 revisions were performed in 14 patients (58 percent). Six
      patients required multiple procedures. Operative revisions included 12 skin level
      revision for stenosis, 11 operations for valve repairs, and 1 each for peristomal
      hernia repair, stomal relocation, and pouch repair for fistulas. Two patients had
      their pouches removed (Crohn's disease and inability to manage pouch). The need
      for revision by 12 months was 29 percent, and the average time period before the
      first revision was 24 months (range, 4 days to 109 months). The overall failure
      rate (converted to conventional ileostomy) was only 8.3 percent. Ninety percent
      of the patients have continent pouches and are satisfied with their pouch
      function. CONCLUSIONS: Continent ileostomies continue to have a high rate of
      reoperations, reasonable functional results, and are a viable option for failed
      ileal pouch-anal pouch patients. Surgeons electing to perform continent
      ileostomies must carefully select their patients and advise them of the high
      potential for reoperations. Despite a high reoperation rate, patients are pleased
      with their continent ileostomies.

PMID- 15959721
TI  - Risperidone-induced action potential prolongation is attenuated by increased
      repolarization reserve due to concomitant block of I(Ca,L).
AB  - The neuroleptic risperidone is an effective blocker of the rapidly activating
      component of the delayed rectifier current (I(Kr)) and hence is expected to
      prolong cardiac action potential duration (APD). However, unlike with other
      typical I(Kr) blockers we failed to demonstrate a marked prolongation of late
      repolarization with risperidone. It is hypothesized that the APD-prolonging
      effect of risperidone is masked by the high repolarization reserve due to the
      prominent delayed rectifier currents I(Kr) and I(Ks) in guinea pig papillary
      muscle. Action potentials and force of contraction were recorded in isolated
      guinea pig papillary muscles. L-type calcium current I(Ca,L) and I(Kr) were
      measured using the standard patch clamp technique in single ventricular
      cardiomyocytes. Reduction of the repolarization reserve by the blocking of I(Ks)
      with chromanol 239B augmented the effect of the selective I(Kr) blocker E-4031,
      but not of risperidone, although both drugs completely blocked I(Kr). In contrast
      to E-4031 risperidone markedly reduced the force of contraction due to the
      partial blocking of I(Ca,L) in the same concentration range as required for block
      of I(Kr). Reduction of the repolarization reserve by the blocking of I(Ks) cannot
      exacerbate the APD-prolonging effect of risperidone. However, even incomplete
      concomitant blocking of I(Ca,L) attenuates the APD-prolonging effect of the
      complete blocking of I(Kr). This behaviour may explain the small APD-prolonging
      effect of risperidone despite the drug's robust blocking of I(Kr).

PMID- 15959722
TI  - Haptic shape discrimination in humans: insight into haptic frames of reference.
AB  - This study investigates how a change in the physical relation between objects
      (two-dimensional, 2-D, angles) and a subject, as well as scanning conditions,
      modify the ability to discriminate small changes in 2-D shape. Subjects scanned
      pairs of angles (90 masculine standard; 91 masculine-103 masculine comparison
      angles) with the right index finger of the out-stretched arm, identifying the
      larger of each pair. When joint rotation was restricted to the shoulder, the
      discrimination threshold significantly increased when the angles were explored
      with the shoulder in a more eccentric position rather than closer to the midline
      (60 masculine versus 30 masculine to the right). This result was attributed to
      changes in proprioceptive sensitivity, since explorations restricted to distal
      joints (wrist/second metacarpophalangeal joint) showed no change with shoulder
      position. The results showed, moreover, that discrimination threshold was similar
      for distal and proximal joints when the delay between scanning the pairs of
      angles was long (15 s). This observation suggests that regional variations in
      proprioceptive acuity (proximal>distal) may reflect an adaptation to generate an
      invariant central representation of haptic shape. Using a shorter interscan delay
      (5 s), a position-dependent increase in discrimination threshold was revealed for
      distal explorations, an effect that disappeared when the head was turned in the
      direction of the unseen angle (vision occluded). We suggest that these results
      can be explained by the existence of two competing egocentric frames of reference
      with different time courses, one of short duration that is centred on the
      arm/hand, and a second of longer duration centred on the head. At the short
      delay, the reference frames interacted to distort the haptic representation when
      they were misaligned. This distortion was resolved at the long delay, possibly
      through suppression of the arm/hand-centred reference frame.

PMID- 15959724
TI  - Long-term outcome of kidney function after twin-twin transfusion syndrome treated
      by intrauterine laser coagulation.
AB  - Twin-twin transfusion syndrome (TTTS) is caused by unbalanced shunting of blood
      between monochorionic twins. It is well known that chronic hypotension and
      hypovolemia may cause renal insufficiency in the donor twin. The long-term
      outcome of kidney function after TTTS has not previously been delineated in the
      literature, however. The aim of this study was to evaluate the long-term outcome
      of kidney function in children after intrauterine laser treatment for severe
      TTTS. Eighteen surviving twin pairs after intrauterine laser treatment for TTTS
      were involved in the study. Their gestational age at birth was 29-39 weeks, their
      median birth weight was 2050 g, and their median age at evaluation was 3 years 1
      month, range 1 year 9 months to 4 years 5 months. Serum creatinine, cystatin C,
      and beta 2-microglobulin, sodium, potassium, and phosphate excretion, and urine
      albumin and alpha-1-microglobulin were measured. Creatinine clearance was
      calculated by use of the Schwartz formula. The laboratory findings for all 36
      children were within normal limits. There were no significant differences between
      donors and recipients. Despite severe alteration of renal function before the
      laser treatment (anuria-polyuria) no long-term impairment of renal function could
      be detected in any of the 18 twin pairs.

PMID- 15959723
TI  - ooc1, a unique gene expressed only during growth of Hypocrea jecorina (anamorph:
      Trichoderma reesei) on cellulose.
AB  - To grow on cellulose as a carbon source, Hypocrea jecorina (Trichoderma reesei)
      expresses and secretes a number of cellulases. This mechanism of induction by an
      insoluble carbon source has been controversially explained, but is most
      frequently attributed to the formation of the beta-1,2-diglucoside sophorose, a
      powerful soluble inducer of cellulases, by means of transglycosylation by
      constitutive or conidia-bound beta-glycoside hydrolases. Some recent results,
      however, have put the role of sophorose as the mediator of cellulose induction in
      question. Here we used the rapid subtraction hybridization approach to clone
      genes expressed by H. jecorina in the presence of cellulose but not upon
      incubation with sophorose. From a total of 96 expressed sequence tag (EST)
      fragments, 37 putative positives--representing ten different genes--were selected
      and analysed. All of them were present in the genome sequence of H. jecorina.
      Three of them encode proteins known from H. jecorina, five encode enzymes
      involved in secondary metabolism and one gene encodes an as yet unknown member of
      glycoside hydrolase family 30. Two EST fragments had no orthologues in other
      fungi. One of them made up for 25 of the 37 EST fragments analysed. The
      corresponding gene (only expressed on cellulose, ooc1) encodes a small secreted
      10.5-kDa protein. The ooc1 transcript is only detectable during growth on
      cellulose in darkness, but not on cellulose in light or in the presence of other
      cellulase inducers (sophorose, lactose), nor is it formed during growth on
      glucose or glycerol. Its expression is strongly reduced, but not completely
      abolished in the cellulase non-inducible mutant QM 9978. The results of this
      study provide evidence that induction of gene expression by cellulose does not
      necessarily correlate with that by sophorose.

PMID- 15959726
TI  - Surface adsorption, intracellular accumulation and compartmentalization of Pb(II)
      in batch-operated lagoons with Salvinia minima as affected by environmental
      conditions, EDTA and nutrients.
AB  - The effects of environmental factors and nutrients on the various possible
      removal mechanisms (surface adsorption, intracellular accumulation and
      precipitation to sediments) and partitioning of lead among various compartments
      (plant biomass, water column and sediments) in Salvinia minima batch-operated
      lagoons, were evaluated. Surface adsorption was found to be the predominant
      mechanism for Pb(II) removal under all environmental conditions tested in the
      absence of nutrients (an average of 54.3%) and in a nutrient medium (modified
      Hutner 1/10 medium) free of EDTA and phosphates (54.41%) at "high" initial Pb(II)
      concentrations (in the range of 10.3+/-0.13 to 15.2+/-0.05 mg/L). Under these
      conditions, the bioconcentration factors (BCFs) were 2,431+/-276 and 2,065+/-35,
      respectively. Lead removal was very rapid during the first 4 h and reached 70% in
      the absence of nutrients at the "medium" light intensity and temperature (LIT)
      tested, 88% in nutrient medium free of EDTA and supplemented with synthetic
      wastewater (at the "lowest" LIT tested), and 85% in medium free of EDTA and
      phosphates. It was concluded that the mechanisms of lead removal by S. minima,
      and the compartmentalization of this metal in the microcosm of batch-operated
      lagoons, are primarily a function of the presence of certain nutrients and
      chelants, with secondary dependence on environmental conditions. In addition, the
      results indicate that the percentage of lead removed is only a gross parameter
      and that the complementary use of BCF and compartmentalization analysis is
      required to gain a full insight into the metal removal process.

PMID- 15959725
TI  - Biochemical and molecular characterization of a tetrachloroethene dechlorinating
      Desulfitobacterium sp. strain Y51: a review.
AB  - A strict anaerobic bacterium, Desulfitobacterium sp. strain Y51, is capable of
      very efficiently dechlorinating tetrachloroethene (PCE) via trichloroethene (TCE)
      to cis-1,2-dichloroethene (cis-DCE) at concentrations as high as 960 microM and
      as low as 0.06 microM. Dechlorination was highly susceptible to air oxidation and
      to potential alternative electron acceptors, such as nitrite, nitrate or sulfite.
      The PCE reductive dehalogenase (encoded by the pceA gene and abbreviated as PceA
      dehalogenase) of strain Y51 was purified and characterized. The purified enzyme
      catalyzed the reductive dechlorination of PCE to cis-DCE at a specific activity
      of 113.6 nmol min(-1) mg protein(-1). The apparent K(m) values for PCE and TCE
      were 105.7 and 535.3 microM, respectively. In addition to PCE and TCE, the enzyme
      exhibited dechlorination activity for various chlorinated ethanes such as
      hexachloroethane, pentachloroethane, 1,1,1,2-tetrachloroethane and 1,1,2,2
      tetrachloroethane. An 8.4-kb DNA fragment cloned from the Y51 genome revealed
      eight open reading frames, including the pceAB genes. Immunoblot analysis
      revealed that PceA dehalogenase is localized in the periplasm of Y51 cells.
      Production of PceA dehalogenase was induced upon addition of TCE. Significant
      growth inhibition of strain Y51 was observed in the presence of cis-DCE, More
      interestingly, the pce gene cluster was deleted with high frequency when the
      cells were grown with cis-DCE.

PMID- 15959727
TI  - Purification, characterization, gene cloning and nucleotide sequencing of D: 
      stereospecific amino acid amidase from soil bacterium: Delftia acidovorans.
AB  - The D-amino acid amidase-producing bacterium was isolated from soil samples using
      an enrichment culture technique in medium broth containing D-phenylalanine amide
      as a sole source of nitrogen. The strain exhibiting the strongest activity was
      identified as Delftia acidovorans strain 16. This strain produced intracellular D
      amino acid amidase constitutively. The enzyme was purified about 380-fold to
      homogeneity and its molecular mass was estimated to be about 50 kDa, on sodium
      dodecyl sulfate polyacrylamide gel electrophoresis. The enzyme was active
      preferentially toward D-amino acid amides rather than their L-counterparts. It
      exhibited strong amino acid amidase activity toward aromatic amino acid amides
      including D-phenylalanine amide, D-tryptophan amide and D-tyrosine amide, yet it
      was not specifically active toward low-molecular-weight D-amino acid amides such
      as D-alanine amide, L-alanine amide and L-serine amide. Moreover, it was not
      specifically active toward oligopeptides. The enzyme showed maximum activity at
      40 degrees C and pH 8.5 and appeared to be very stable, with 92.5% remaining
      activity after the reaction was performed at 45 degrees C for 30 min. However, it
      was mostly inactivated in the presence of phenylmethanesulfonyl fluoride or Cd2+,
      Ag+, Zn2+, Hg2+ and As3+ . The NH2 terminal and internal amino acid sequences of
      the enzyme were determined; and the gene was cloned and sequenced. The enzyme
      gene damA encodes a 466-amino-acid protein (molecular mass 49,860.46 Da); and the
      deduced amino acid sequence exhibits homology to the D-amino acid amidase from
      Variovorax paradoxus (67.9% identity), the amidotransferase A subunit from
      Burkholderia fungorum (50% identity) and other enantioselective amidases.

PMID- 15959728
TI  - Fed-batch fermentation for production of Kluyveromyces marxianus FII 510700
      cultivated on a lactose-based medium.
AB  - A strain of Kluyveromyces marxianus was grown in batch culture in lactose-based
      media at varying initial lactose concentrations (10-60 g L(-1)) at 30 degrees C,
      pH 5.0, dissolved oxygen concentrations greater than 20%. Increasing the
      concentration of mineral salts three-fold at 40 g L(-1) and 60 g L(-1) initial
      lactose concentration showed only a small increase in the yield of biomass, from
      0.38 g g(-1) to 0.41 g g(-1), indicating that the initial batch cultures were not
      significantly nutrient- (mineral salts)-limited. A relatively high biomass
      concentration (105 g L(-1)) was obtained in fed-batch culture following extended
      lactose feeding. An average specific growth rate (0.27 h(-1)), biomass yield
      (0.38 g g(-1)) and overall productivity (2.9 g L(-1) h(-1)) were obtained for
      these fed-batch conditions. This fed-batch protocol provides a strategy for
      achieving relatively high concentrations and productivities of K. marxianus on
      other lactose-based substrate streams (e.g., whey) from the dairy industry.

PMID- 15959729
TI  - Simple oligomers as antimicrobial peptide mimics.
AB  - New approaches to antibiotic design are desperately needed. The design of simple
      oligomers that capture the shape and biological function of natural antimicrobial
      peptides could prove to be versatile and highly successful. We discuss the use of
      aromatic backbones to design facially amphiphilic (FA) beta-sheet like structures
      which are potently antimicrobial. These oligomers capture the physiochemical
      properties of peptides like the Magainins and Defensins, which fold into specific
      conformations that are amphiphilic resulting in antimicrobial activity. However,
      natural peptides are expensive to prepare and difficult to produce on large
      scale. The design of polymers and oligomers that mimic the complex structures and
      remarkable biological properties of proteins is an important endeavor and
      provides attractive alternatives to the difficult synthesis of natural peptides.
      We therefore have designed a series of FA oligomers that are easy to prepare from
      inexpensive monomers. They adopt structures very reminiscent of amphiphilic beta
      sheets and have significant activity with minimal inhibitory concentrations at 6
      h in the low microgram per ml range (muM to nM). They are active against a broad
      spectrum of bacteria including gram-positive and gram-negative as well as
      antibiotic resistant strains.

PMID- 15959730
TI  - Developmental pattern formation of somatic embryos induced in cell suspension
      cultures of cowpea [Vigna unguiculata (L.) Walp].
AB  - The sequence of events in the functional body pattern formation during the
      somatic embryo development in cowpea suspensions is described under three heads.
      Early stages of somatic embryogenesis were characterized by both periclinal and
      anti-clinal cell divisions. Differentiation of the protoderm cell layer by
      periclinal divisions marked the commencement of somatic embryogenesis. The most
      critical events appear to be the formation of apical meristems, establishment of
      apical-basal patterns of symmetry, and cellular organization in oblong-stage
      somatic embryo for the transition to torpedo and cotyledonary-stage somatic
      embryos. Two different stages of mature embryos showing distinct morphology,
      classified based on the number of cotyledons and their ability to convert into
      plantlets, were visualized. Repeated mitotic divisions of the sub-epidermal cell
      layers marked the induction of pro-embryogenic mass (PEM) in the embryogenic
      calli. The first division plane was periclinally-oriented, the second anti
      clinally-oriented, and the subsequent division planes appeared in any direction,
      leading to clusters of pro-embryogenic clumps. Differentiation of the protoderm
      layer marks the beginning of the structural differentiation in globular stage.
      Incipient pro-cambium formation is the first sign of somatic embryo transition.
      Axial elongation of inner isodiametric cells of the globular somatic embryo
      followed by the change in the growth axis of the pro-cambium is an important
      event in oblong-stage somatic embryo. Vacuolation in the ground meristem of
      torpedo-stage embryo begins the process of histodifferentiation. Three major
      embryonic tissue systems; shoot apical meristem, root apical meristem, and the
      differentiation of pro-cambial strands, are visible in torpedo-stage somatic
      embryo. Monocotyledonary-stage somatic embryo induced both the shoot apical
      meristem and two leaf primordia compared to the ansiocotyledonary somatic embryo.

PMID- 15959731
TI  - In vitro somatic embryogenesis from cell suspension cultures of cowpea [Vigna
      unguiculata (L.) Walp].
AB  - We report, an efficient protocol for plantlet regeneration from the cell
      suspension cultures of cowpea through somatic embryogenesis. Primary leaf
      derived, embryogenic calli initiated in MMS [MS salts (Murashige and Skoog 1962)
      with B5 (Gamborg et al. 1968) vitamins] medium containing 2,4
      Dichlorophenoxyacetic acid (2,4-D), casein hydrolysate (CH), and L: -Glutamic
      acid-5-amide (Gln). Fast-growing embryogenic cell suspensions were established in
      0.5 mg l(-1) 2,4-D, which resulted in the highest recovery of early stages of
      somatic embryos in liquid MMS medium. Embryo development was asynchronous and
      strongly influenced by the 2,4-D concentration. Mature monocotyledonary-stage
      somatic embryos were induced in liquid B5 medium containing 0.1 mg l(-1) 2,4-D,
      20 mg l(-1) L: -Proline (Pro), 5 muM Abscisic acid (ABA), and 2% mannitol. B5
      medium was found superior for the maturation of somatic embryos compared to MS
      and MMS media. The importance of duration (5 d) for effective maturation of
      somatic embryos is demonstrated. A reduction in the 2,4-D level in suspensions
      increased the somatic embryo induction and maturation with decreased
      abnormalities. Sucrose was found to be the best carbon source for callus
      induction while mannitol for embryo maturation and maltose for embryo
      germination. Extension of hypocotyls and complete development of plantlet was
      achieved in half-strength B5 medium supplemented with 3% maltose, 2500 mg l(-1)
      potassium nitrate, and 0.05 mg l(-1) thidiazuron (TDZ) with 32% regeneration
      frequency. Field-established plants were morphologically normal and fertile. This
      regeneration protocol assures a high frequency of embryo induction, maturation,
      and plantlet conversion.

PMID- 15959732
TI  - Childhood craniopharyngioma: Vancouver experience.
AB  - OBJECTIVE: To present our institution's experience in the management of childhood
      craniopharyngioma since 1982. METHODS: We retrospectively reviewed the records of
      all children diagnosed with craniopharyngioma at our children's hospital from its
      opening in 1982 through to 2003. One neuroradiologist systematically reviewed the
      neuroimaging. Kaplan-Meier curves were used to analyze the progression-free
      survival and the overall survival from the time of the first definitive
      intervention. CONCLUSIONS: Most children diagnosed with craniopharyngioma are
      long-term survivors. Survivors suffer from multiple deficits in the long term. A
      conservative surgical and radiotherapeutic approach and avoiding interventions
      that are known to cause severe morbidity may minimize these. The use of
      intracystic bleomycin is a strategy that allows the delay of more aggressive
      therapies in select patients.

PMID- 15959733
TI  - Craniopharyngioma in childhood: our evidence-based approach to management.
AB  - OBJECTIVES: In 1996 we published our results for treatment of childhood
      craniopharyngioma. That study did not only reveal that there was a significant
      morbidity associated with our then policy of attempted radical removal followed
      by post-operative radiotherapy in those cases with residual disease, but also
      that risk factors for poor outcome could be identified based on the clinical and
      radiological findings at presentation. As result of that study, we redefined the
      role of radical surgery in the treatment of craniopharyngioma and developed a new
      treatment strategy in an attempt to improve the quality of outcome without
      compromising tumour control. Our aims in this paper were to compare the results
      of our current treatment strategy with that reported in the 1996 paper to assess
      whether we have achieved this goal. METHODS: A detailed assessment of the
      treatment pathway and outcome was undertaken for children treated for
      craniopharyngioma in our unit from 1996 to 2004. This included a morbidity score
      based on visual, motor, cognitive, hypothalamic and endocrinological data
      obtained from our neuro-oncology database and review of clinical records. Where
      possible we have attempted to record data in the same manner as for our previous
      study allowing for meaningful comparison. RESULTS: Forty-eight children with
      craniopharyngioma presented in the study period. On the basis of clinical
      presentation and radiological findings, 25 were deemed suitable for attempted
      radical surgery and 23 were treated with various subtotal surgical procedures.
      Radiotherapy was used in patients over the age of 5 years where residual tumour
      was present or progressed after the initial surgical intervention(s). Morbidity
      scores, particularly in relation to visual and cognitive outcome, are improved
      and there was no surgical mortality in the current series. CONCLUSIONS: A
      treatment paradigm for childhood craniopharyngioma is presented which improves
      the quality of outcome without compromising tumour control.

PMID- 15959734
TI  - Early adjuvant radiotherapy toward long-term survival and better quality of life
      for craniopharyngiomas--a study in single institute.
AB  - OBJECTIVES: The objective of the study is to compare survival and quality of life
      (QoL) by the delivery time of adjuvant radiotherapy (RT), early or late, for
      craniopharyngiomas. METHODS AND MATERIALS: Fifty patients received RT between
      1985 and 2002. Early RT (n=25) was delivered within 3 months after initial
      surgery, whereas late RT (n=25) was combined with or without reoperation after
      progression or relapse. Radiation dose ranged from 45 to 55.8 Gy with a median of
      54 Gy. The median follow-up was 130 months. RESULTS: Progression-free survival
      rates at 5 and 10 years were 95.9 and 91.2%, respectively. The overall or
      progression-free survival was not influenced by RT time. Initial tumor size was
      the only prognostic factor (p=0.034) for progression-free survival in univariate
      analysis. Better visual acuity or field was maintained, and diabetes insipidus
      was partly improved with early RT, but all were deteriorated as tumor progressed
      without early RT. Visual functions were not worsened after late RT. CONCLUSIONS:
      The survival was excellent with adjuvant RT, early or late. Poor QoL with late RT
      resulted from relapsed tumor and repeated surgery but was not associated with RT
      itself. Thus, early RT with precision technique is highly recommended for better
      QoL and excellent survival, unless contraindicated.

PMID- 15959736
TI  - Cervical spina bifida cystica: MRI differentiation of the subtypes in children.
AB  - BACKGROUND: Cervical spinal dysraphism is a rare condition with only 37 cases
      reported in the literature, of which only seven patients had undergone
      preoperative magnetic resonance imaging (MRI). OBJECTIVE: By using illustrative
      cases, we demonstrate the value of MRI in distinguishing the two different
      subtypes of cervical spinal dysraphism, namely, myelocystocele and meningocele.
      METHOD: Retrospective review of the MRI scans of six patients with cervical (one
      high thoracic) posterior cystic swellings, which were diagnosed as cervical
      dysraphism, was done. RESULTS: Three patients were diagnosed with myelocystocele
      and three patients with meningocele. A comparison of MRI features between the two
      entities, as well as the associated anomalies, is discussed. CONCLUSION: MRI is
      the imaging modality of choice for suspected cervical dysraphism, prior to
      surgery. It helps distinguish the subtypes, as well as identify the associated
      anomalies.

PMID- 15959735
TI  - The Geneva and Lausanne (French-speaking Switzerland) experience: in favor of the
      transsphenoidal approach when feasible.
AB  - BACKGROUND: The authors present their current attitude towards management of
      craniopharyngiomas in children. Radical surgery cannot be performed when one is
      not sure about its potential danger to the visual pathways and the hypothalamus.
      METHODS: Most of the surgeries that have been performed in our institution via an
      intracranial approach were incomplete and followed by radiotherapy, in the last
      10 years with stereotactic conformational radiotherapy. DISCUSSION: Considering
      our past and present experience concerning the transphenoidal approach for
      treatment of craniopharyngiomas, we make a plea for the consideration of this
      approach in children whenever feasible (around 25% of the cases in children older
      than 5 years). Craniopharyngiomas that can be removed by this approach represent
      a milder form of the disease and the results concerning the visual, hypothalamic
      functions and quality of life are significantly better than that obtained via an
      intracranial approach. When the craniopharyngioma cannot be removed by this
      approach because of tight hypothalamic adherences, the technique of
      cystosphenoidostomy with a custom-made shunt plus adjuvant stereotactic
      conformational radiotherapy is an alternative for its total removal.

PMID- 15959737
TI  - Acetazolamide and corticosteroid therapy in complicated arachnoid cyst.
AB  - CASE REPORT: We report on the successful conservative treatment of a child
      harbouring a right-temporal arachnoid cyst associated with bilateral hygroma.
      TREATMENT: Medical treatment was by corticosteroids for several days and
      acetazolamide (15 mg/kg/die) for 10 months. OUTCOME: Clinical symptoms and signs
      disappeared completely with partial resolution of the bilateral hygroma at MRI
      follow-up.

PMID- 15959738
TI  - Coats' disease and bilateral cataract in a child with Turner syndrome: a case
      report.
AB  - PURPOSE: To report the first case in which Coats' disease was observed with
      infantile cataract in a girl with Turner syndrome (TS). MATERIALS AND METHODS: We
      examined a 4-year-old female infant with TS who was referred with a diagnosis of
      leukocoria in the left eye. RESULTS AND DISCUSSION: Examination under anaesthesia
      revealed a bilateral punctate cataract and left eye fundus showed vascular
      retinal abnormalities typical of Coats' disease. Cryotherapy was performed on the
      telangiectatic vessels and the child was followed up for a period of 12 months.
      Despite cryotherapy resulting in regression of the peripheral exudates, an
      exudative maculopathy persisted with poor visual outcome. We suggest that Coats'
      disease should be considered as a rare ocular manifestation in TS.

PMID- 15959739
TI  - An 18-month follow-up study on vibrotactile sense, muscle strength and symptoms
      in computer users with and without symptoms.
AB  - OBJECTIVES: The aim was to explore whether symptoms, sensory perception and
      muscle strength among computer users with and without symptoms in forearm or hand
      had changed after 18 months. METHODS: Twenty-six out of 30 females, experienced
      computer users, from a baseline study participated in the follow-up. In addition,
      five control subjects participated. The subjects completed a questionnaire
      regarding exposure to computer work, prevalence and severity of symptoms, health
      status and physical activity. Perceived thresholds for vibration were measured
      twice with 3 h in between on the right hand on four different sites innervated by
      the radial, median or ulnar nerve. Furthermore, sensory perception was measured
      on the left hand on two sites innervated by the median and ulnar nerve,
      respectively. Skin temperature was measured at each site prior to sensory
      perception measurements. Maximal handgrip strength and maximal pinch-grip
      strength were measured for both hands. RESULTS: Eighty-three percent of the
      subjects who had symptoms at baseline still had symptoms and 21% of the subjects
      who did not have symptoms at baseline experienced symptoms at follow-up. The
      first and the second sensory perception measurement were highly correlated.
      Vibrotactile sensory threshold representing the radial nerve was increased since
      baseline among the subjects who originally had symptoms. At follow-up, the
      vibrotactile sense for the computer users who reported symptoms in forearm or
      hand at baseline was deteriorated for the sites representing the median, ulnar
      and radial nerves compared to the control group. Among the original symptom free
      subjects with intensive computer work increases in vibrotactile perception
      thresholds were found for the sites representing the median and ulnar nerves.
      Handgrip muscle strength remained unchanged for all groups. CONCLUSIONS: The
      study indicates that sensory dysfunctions as well as symptoms in forearm and hand
      among computer users to a high degree are persistent. Muscle strength seems to be
      well maintained.

PMID- 15959740
TI  - Evaluation of effective return-to-work treatment programs for sick-listed
      patients with non-specific musculoskeletal complaints: a systematic review.
AB  - OBJECTIVE: This systematic review seeks to gain insight into the effectiveness of
      return-to-work treatment programs among sick-listed patients with non-specific
      musculoskeletal complaints. The focus here lies on the composition of effective
      treatment programs, itemized for regional non-specific musculoskeletal
      complaints. METHODS: A systematic literature search was performed and
      methodological quality criteria were applied. RESULTS: Eighteen high quality
      articles were selected, which reported on a combined total of 22 treatment
      programs, including a total of 3,579 participants. Of these 22 treatments
      programs, seven experimental treatments (32%) resulted in faster return to work
      compared to the control treatment. None of the studies reviewed reported negative
      findings. What appeared to be essential to effective treatment was knowledge
      conditioning, psychological, physical and work conditioning, possibly
      supplemented with relaxation exercises. Most of the high quality studies (64%)
      reported on a low back pain population. CONCLUSION: The findings were
      inconsistent regarding the effectiveness of treatment programs in enabling sick
      listed patients with non-specific musculoskeletal disorders to return to work.
      Except for low back pain, none of the studies explicitly itemized the effects of
      treatment programs on return to work by regional musculoskeletal disorders, such
      as upper extremity musculoskeletal disorders.

PMID- 15959741
TI  - Decreases in urine specific gravity and urinary creatinine in elderly women.
AB  - OBJECTIVE: To examine the effects of aging on urinary levels of creatinine (CR)
      and urine specific gravity (SG) among women in a large-scale epidemiology survey.
      METHODS: Data on CR and SG in urine, together with smoking habits and menopausal
      status, were selected from previously established databases and combined with the
      results of supplemental sample collection. In total, CR and SG data were
      available for 11,090 never-smoking women (total group; 29-80 years of age); a
      subgroup of 1,851 women who lived in Kyoto was also selected from the total
      group. Data from the two groups were subjected to statistical analyses. In
      statistical evaluation, SG was converted to factor G, which was defined as (SG
      1.000)x1,000. RESULTS: Classification by decade of years of age showed that both
      CR and SG decreased steadily as a function of advancement in age over 30 years,
      both in the total group and in the Kyoto subgroup, showing high reproducibility
      of the observation on a whole-country basis and on a local basis. When the levels
      at 80 years of age were compared with those at 30 years, there was an
      approximately 60% and 30% decrease in CR and factor G, respectively. Thus, the
      effects of aging were more marked on CR than on factor G (and therefore on SG).
      Menopause appeared to be an influential factor in the reduction of CR and SG,
      separately from aging itself. CONCLUSIONS: Urinary levels of creatinine and, to a
      lesser extent, urine specific gravity, steadily decreased as a function of ages
      of over 30 years in women.

PMID- 15959742
TI  - [Controlling systems for operating room managers].
AB  - Management means developing, shaping and controlling of complex, productive and
      social systems. Therefore, operating room managers also need to develop basic
      skills in financial and managerial accounting as a basis for operative and
      strategic controlling which is an essential part of their work. A good
      measurement system should include financial and strategic concepts for market
      position, innovation performance, productivity, attractiveness, liquidity/cash
      flow and profitability. Since hospitals need to implement a strategy to reach
      their business objectives, the performance measurement system has to be
      individually adapted to the strategy of the hospital. In this respect the
      navigation system developed by Galweiler is compared to the "balanced score card"
      system of Kaplan and Norton.

PMID- 15959743
TI  - [The Wurzburg polytrauma algorithm. Concept and first results of a sliding-gantry
      based computer tomography diagnostic system].
AB  - BACKGROUND: The purpose of this study was to show the practicability of a new
      algorithm in the management of polytraumatized patients based on Advanced Trauma
      Live Support (ATLS) and using mobile whole body multislice CT (MMDCT) as the
      primary imaging system. PATIENTS AND METHODS: A series of 120 trauma patients
      referred to the Wurzburg University Hospital Trauma Emergency Room were
      categorized into suspected polytrauma and suspected non-polytrauma groups. The
      polytraumatized patients were investigated using the Wurzburg polytrauma
      algorithm including whole body multislice CT with a 16-row-scanner. The algorithm
      is described. The time for the diagnostic procedure was measured and compared
      with data from the Trauma Registry of the German Society of Trauma Surgery.
      RESULTS: From 120 patients 78 (66%) underwent whole body CT. The diagnostic
      procedure was quick with significant advantages especially for cranial and trunk
      diagnostics. CONCLUSION: The Wurzburg polytrauma algorithm worked well. There was
      excellent cooperation within the interdisciplinary leading team consisting of
      anaesthesiologists, surgeons, and radiologists. The principles of ATLS could be
      respected. Mobile whole body multislice CT was an effective tool in the
      diagnostic evaluation of polytrauma patients.

PMID- 15959744
TI  - [Bariatric surgery. Patient selection and indication].
AB  - Successful reduction of body weight in patients with morbid obesity (BMI >40
      kg/m(2)) is difficult and on a long-term basis nearly impossible with non
      interventional treatment modalities. Surgical therapy is an efficient alternative
      for these patients. Potential surgical treatment should be carefully evaluated
      during a 6-month preoperative treatment phase during which indications and
      contraindications should be evaluated. Qualified postoperative care must be
      provided.

PMID- 15959746
TI  - [Polytrauma and air rescue. A retrospective analysis of trauma care in eastern
      Austria exemplified by an urban trauma center].
AB  - OBJECTIVE: The aim of this study was a retrospective analysis of polytraumatized
      patients who were treated by a helicopter emergency medical service (HEMS) crew.
      This study was performed to evaluate the level of prehospital care provided for
      severely injured patients. Special consideration was given to treatment
      strategies of specific injuries which led to multiple injuries, defined as
      "polytrauma." METHODS: From September 1992 to April 2001 data of 386 patients
      treated in the Department of Traumatology of the University of Vienna were
      collected. A total of 104 patients (26.9%) were transported by helicopter
      directly from the accident scene. This collective was analyzed demographically;
      relevant prehospital data such as therapeutic interventions and the early
      clinical course were examined. RESULTS: The mean Injury Severity Score (ISS) was
      36.9: 70 (67.3%) patients were male and 34 (32.7%) female; the median age was
      36.1 years. Traffic accidents were the most frequent trauma mechanism (78.9%)
      followed by falls from height (17.3%). The mean period between trauma and trauma
      emergency room was 0.73 h; 77 (74.0%) patients were intubated and mechanically
      ventilated at the scene and all patients received analgosedation. The mean
      preclinical fluid load was 1673 ml. The mean duration of treatment in the
      emergency room was 53 min. The mean length of intensive care was 8.6 days and the
      mortality rate was 19.2% within the first 24 h. CONCLUSION: Major trauma is an
      important cause for requesting a primary HEMS mission. As the results of this
      study show, immediate and invasive interventions at the scene lead to an
      improvement of vital functions at admission. For the patients' further course of
      treatment, the choice of a trauma center seems to be important, too.

PMID- 15959745
TI  - [Reaming debris: a source of vital cells! First results of human specimens].
AB  - Reaming debris is generated in the course of intramedullary reaming of long
      bones. Up to now there has been little information about the composition of
      reaming debris. Especially, it remains to be elucidated if reaming debris
      contains vital cells. The goal of the present vitro investigation has been the
      harvest of cells from human reaming debris and the subsequent characterization of
      the cells. 21 specimens of human reaming debris have been investigated. Each
      specimen has been divided into two parts. One part has been examined by means of
      transmission electron microscopy while the other part of each specimen has been
      transferred into culture dishes. The developing cell cultures were characterized
      by using FACS analysis and were incubated within osteogenic, adipogenic and
      chondrogenic differentiation media. The results of electron microscopy have
      revealed the presence of both, vital cells and massively altered cells. Cell
      growth occurred after initial plating of all specimens. The cells which were
      grown within the culture dishes could be characterized as mesenchymal stem cells
      on the basis of their morphology, differentiation capacity and antigen profile.
      Based upon these results reaming debris has to be regarded as a source of vital
      mesenchymal stem cells. It remains to be elucidated, if reaming debris can be
      used as an alternative to bone tissue grafting.

PMID- 15959747
TI  - [Complete rupture of the proximal semimembranosus tendon. Minimally invasive
      surgical repair by use of a suture anchor in a rare but often underestimated
      injury].
AB  - Complete rupture of the proximal semimembranosus tendon is a rare injury
      associated with significant functional loss. Conservative treatment has proven
      inadequate in returning patients to their previous activity level. However,
      diagnosis is often delayed because of underestimation of the severity of this
      injury. Satisfactory results can be achieved with both early and late surgical
      tendon repair in the majority of cases. However, repair delayed by more than 4
      weeks post trauma usually requires extended mobilisation of the injured muscle
      and neurolysis of the sciatic nerve. Therefore, we recommend surgical repair as
      early as possible. We report on the successful minimally invasive surgical repair
      of a complete rupture of the proximal semimembranosus tendon by use of a suture
      anchor 18 days after injury.

PMID- 15959748
TI  - [Percutaneous technique for Achilles tendon repair with the Dresden Instruments].
AB  - BACKGROUND: The percutaneous technique for Achilles tendon repair with the
      Dresden instruments (pDI suture) was developed to minimize the typical problems
      of percutaneous Achilles tendon sutures. METHODS: From 1 January 2000 to 31
      December 2003, the pDI suture was performed in 61 patients with 62 Achilles
      tendon ruptures. We reviewed 39 of 47 patients (83%) with 40 ruptured Achilles
      tendons who had undergone percutaneous repair at a minimal interval of 12 months
      after the operation. RESULTS: In this study we observed no sural nerve injuries.
      The rerupture rate was 2/62 or 3.2%. In one patient (1.6%) a superficial late
      infection occurred after tendon healing. Using the criteria of Trillat and
      Mounier-Kuhn, 62% of the results were very good and 30% good. The average AOFAS
      score was 96 (78-100) points; 78% of the patients assessed the result of
      treatment as very good and 20% as good. CONCLUSIONS: The percutaneous suture
      using the Dresden instruments is a minimally invasive operative treatment of
      Achilles tendon rupture resulting in nearly all very good and good subjective and
      clinical results. It combines a low rerupture and infection rate with a minimized
      risk of sural nerve injury.

PMID- 15959749
TI  - [Presenile dementia in memory clinics--incidence rates and clinical features].
AB  - This study describes the clinical features of presenile dementia diagnosed in
      memory clinics. It further gives an estimate of the declared incidence for the
      German city of Munich and surrounding counties. Twelve memory clinics in
      Switzerland and Germany were considered, among them all of the four in Munich. A
      total of 267 patients with onset of illness under the age of 65 were included.
      Only 16 patients (6%) were younger than 50. Men and women were affected about
      equally often. The most common cause of dementia was Alzheimer's disease (67%),
      followed by frontotemporal degeneration (13.5%) and vascular (5.6%) dementia. The
      declared incidence was estimated at 8.3 new cases of dementia per year among
      100,000 persons in the 50-64 age range, with an incidence rate of Alzheimer's
      disease at 6.3/100,000. It can be concluded that memory clinics fulfill an
      important function in the care of patients with presenile dementia, since they
      are highly utilized by younger patients in early stages of the illness.

PMID- 15959750
TI  - [Classification of Wilson's disease based on neurophysiological parameters].
AB  - In addition to hepatolenticular degeneration in Wilson's disease, sensory and
      extrapyramidal motoric systems are also disturbed. In this study a classification
      on the basis of neurophysiological parameters (EAEP, VEP, MSEP, TSEP and MEP) was
      established according to subclinical disturbances of these pathways in patients
      with Wilson's disease on long-term treatment. A cluster analysis of latencies of
      these evoked potentials was performed. The results of cluster analysis revealed
      three types of electrophysiological profiles: type I with normal latencies and
      types II and III showing different patterns of prolonged latencies. However,
      there was no correlation between clinical classification and the results of
      cluster analysis based on the electrophysiological data. The neurophysiological
      based classification provides additional information about central manifestations
      and aids in characterizing the progress of the disease.

PMID- 15959751
TI  - [Neurotoxic encephalopathy caused by neuroleptics and lithium].
AB  - Treatment of psychiatric patients often necessitates overlapping neuroleptic
      medication. We report a 60-year-old woman suffering from a schizoaffective
      disorder who received temporarily three neuroleptics, together with lithium. She
      developed neurotoxic encephalopathy with symptoms of a malignant neuroleptic
      syndrome. It is unclear if irreversible brain damage will remain. We recommend
      frequent electroencephalographic controls for early detection of neurotoxicity.

PMID- 15959753
TI  - [Possibilities for workflow optimization in radiology departments beyond RIS and
      PACS].
AB  - Technological progress and the rising cost pressure on the healthcare system have
      led to a drastic change in the work environment of radiologists today. The
      pervasive demand for workflow optimization and increased efficiency of its
      activities raises the question of whether by employment of electronic systems,
      such as RIS and PACS, the potentials of digital technology are sufficiently used
      to fulfil this demand. This report describes the tasks and structures in
      radiology departments, which so far are only insufficiently supported by
      commercially available electronic systems but are nevertheless substantial. We
      developed and employed a web-based, integrated workplace system, which simplifies
      many daily tasks of departmental organization and administration apart from well
      established tasks of documentation. Furthermore, we analyzed the effects exerted
      on departmental workflow by employment of this system for 3 years.

PMID- 15959755
TI  - [Necrosis of the carpal scaphoid after chemotherapy. Case report].
AB  - Preiser's disease--first described by Preiser in 1910--presents the rare
      avascular necrosis of the carpal scaphoid. There is no consensus with regard to
      cause and therapeutic procedure to this day. The initially postulated idiopathic
      origin of the disease is controversial and rare. It is mainly caused by trauma or
      repetitive microtrauma, but can also occur as a complication of drug therapy. The
      rare occurrence of necrosis of the carpal scaphoid following chemotherapy is
      presented. The treatment was resection of the scaphoid and mediocarpal
      arthrodesis. Clinical appearance, diagnostic work-up, and therapy of the disease
      are discussed.

PMID- 15959754
TI  - Activation of opioid mu-receptors by loperamide to improve interleukin-6-induced
      inhibition of insulin signals in myoblast C2C12 cells.
AB  - AIMS/HYPOTHESIS: This study investigated the role of opioid mu-receptor
      activation in the improvement of insulin resistance. METHODS: Myoblast C2C12
      cells were cultured with IL-6 to induce insulin resistance. Radioactive 2
      deoxyglucose (2-DG) uptake was used to evaluate the effect of loperamide on
      insulin-stimulated glucose utilisation. Protein expression and phosphorylation in
      insulin-signalling pathways were detected by immunoblotting. RESULTS: The insulin
      stimulated 2-DG uptake was reduced by IL-6. Loperamide reversed this uptake, and
      the uptake was inhibited by blockade of opioid mu-receptors. Insulin resistance
      induced by IL-6 was associated with impaired expression of the insulin receptor
      (IR), IR tyrosine autophosphorylation, IRS-1 protein content and IRS-1 tyrosine
      phosphorylation. Also, an attenuated p85 regulatory subunit of
      phosphatidylinositol 3-kinase, Akt serine phosphorylation and the protein of
      glucose transporter subtype 4 were observed in insulin resistance. Loperamide
      reversed IL-6-induced decrement of these insulin signals.
      CONCLUSIONS/INTERPRETATION: Opioid mu-receptor activation may improve IL-6
      induced insulin resistance through modulation of insulin signals to reverse the
      responsiveness of insulin. This provides a new target in the treatment of insulin
      resistance.

PMID- 15959756
TI  - [Effect of femoral cementing technique on results. Comparison between retrograde
      technique and vacuum application].
AB  - METHODS: To evaluate the penetration depth of cement into trabecular femoral
      bone, femora of 14 sheep were subjected to simultaneous bilateral cementing.
      After femoral neck osteotomy, preparation of the bone cavities and jet lavage,
      cement was applied simultaneously using the conventional retrograde method for
      one side and vacuum application for the contralateral limb. Bilateral
      simultaneous pressurisation was then applied. All femoral specimens were X-rayed,
      sawed into standardised, horizontal, stereometric, identical slices and
      microradiographed. Cement penetration was assessed using a morphometric software
      system. RESULTS: No significant differences in depth of cement penetration
      between sheep femora cemented with the vacuum application method and the standard
      retrograde method could be found or between the ratio of cement-consolidated and
      non-cement-consolidated cancellous bone. CONCLUSION: The more complicated and
      technically challenging method of cement application under vacuum had no
      advantage in terms of cement interdigitation over the standard retrograde method.

PMID- 15959758
TI  - Comparative costing analysis of intensive care services between Hungary and
      United Kingdom.
AB  - OBJECTIVE: The study presents the findings of the first National Intensive Care
      Cost Block Analysis in Hungary. METHODS: There were 13 Intensive Care Units
      (ICUs) involved in this study: 5 University Hospitals, 6 District County
      Hospitals and 2 City Hospitals. The annual costs of ICUs were measured by "top
      down" approach based on Cost Block Method. Annual expenditure of 3 cost blocks
      was collected for year 2000: clinical support, consumables and staff costs. On
      top of the annual costs, we collected general ICU data and Top 10 drugs of each
      unit. Our data was compared to National Cost Block data of United Kingdom.
      RESULTS: There were 9313 patients involved in the study. The median (IQR) ICU
      occupancy rate was 67% (62-79), mortality was 21% (11-26). The mean cost per bed
      was 30,990 Euro (SD 12,573) and 144 Euro (SD 63,1) per patient day. Clinical
      support services were accounted for 9.6% of resources, consumables for 60.6% and
      staff costs for 29.8%. CONCLUSIONS: Intensive care costs are very low in Hungary
      compared to other European countries. The difference is explained by the cheaper
      staff cost, but the lower number of nurses per ICU bed contributes as well.

PMID- 15959759
TI  - Hypothalamic-pituitary dysfunction in critically ill patients with traumatic and
      nontraumatic brain injury.
AB  - BACKGROUND: A significant number of studies have shown that critically ill
      patients with brain injury (BI) frequently exhibit abnormal pituitary hormonal
      responses during the immediate postinjury period. DISCUSSION: The elucidation of
      endocrine alterations depends on the criteria used, the diagnostic tests applied,
      and the timing of testing in relation to BI. The pattern of the detected hormonal
      abnormalities shows considerable variability. Altered endocrine responses are due
      mostly to hypothalamic changes rather than to pituitary dysfunction. Several
      studies have examined the correlation between hormonal alterations and BI
      severity, but the results are inconsistent. Furthermore, it remains currently
      unclear whether and how pituitary abnormalities adversely affect the clinical
      course of BI patients during the period of critical illness. On the basis of
      current knowledge, with the exception of clinically significant relative adrenal
      deficiency and diabetes insipidus, the other endocrine alterations do not seem to
      require any therapeutic intervention in severely ill BI patients. It is also
      uncertain whether hormonal abnormalities detected in the early post-BI period
      persist for the rest of these patients' lives. CONCLUSIONS: In view of current
      evidence indicating a high incidence of pituitary dysfunction even years
      following BI it is recommended that repetition of endocrine evaluation should be
      performed during the rehabilitation phase in all patients.

PMID- 15959760
TI  - Modified score for disseminated intravascular coagulation in the critically ill.
AB  - OBJECTIVE: To assess the value of the diagnosis of overt disseminated
      intravascular coagulation (DIC) according to the International Society on
      Thrombosis and Haemostasis (ISTH) criteria and that of the parameters included in
      the ISTH score for overt DIC in predicting day 28 mortality in intensive care
      patients. Also, to assess the value of the components of the score in the
      diagnosis of overt DIC. DESIGN AND SETTING: Retrospective clinical study in a
      university hospital intensive care unit. PATIENTS AND PARTICIPANTS: 494
      consecutive patients admitted in the ICU between January 2002 and October 2003.
      MEASUREMENTS AND RESULTS: Clinical and laboratory data, including hemostatic
      parameters, were collected from computerized databases and patient files.
      Altogether 19% (95/494) of the patients fulfilled the criteria for overt DIC.
      Their day 28 mortality rate was higher than that of patients without overt DIC
      (40% vs. 16%). The lowest platelet count (area under curve, AUC, 0.910), highest
      plasma D-dimer (AUC 0.846), lowest antithrombin (AUC 0.823), and Owren-type
      prothrombin time activity (AUC 0.797) discriminated well the patients with and
      without overt DIC, whereas plasma fibrinogen (AUC 0.690) had poor discriminative
      power. No patient with the diagnosis of overt DIC had decreased plasma
      fibrinogen. Day-1 SOFA and APACHE II score, the first CRP measurement, and the
      lowest antithrombin were independent predictors of day 28 mortality. CONCLUSIONS:
      The diagnosis of overt DIC was not an independent predictor of day 28 mortality.
      In ICU patients plasma antithrombin seems a promising candidate in the panel of
      indicators for overt DIC whereas the value of plasma fibrinogen is in doubt.

PMID- 15959761
TI  - Acute pancreatitis, incomplete thrombotic microangiopathy and cocaine abuse: an
      unusual pathogenic link.

PMID- 15959762
TI  - Differential inducible nitric oxide synthase activity in circulating neutrophils
      vs. mononuclears of septic shock patients.
AB  - OBJECTIVE: To compare nitric oxide synthase (NOS) activity in circulating
      neutrophils and mononuclear cells of patients with septic shock to healthy
      subjects. DESIGN AND SETTING: Prospective study in the general intensive care
      unit (30 beds) of a university affiliated-hospital and the A.C. Burton Vascular
      Biology Research Laboratory. PATIENTS: Six septic patients and seven healthy
      volunteers. MEASUREMENTS AND RESULTS: We measured NOS in circulating neutrophils
      and mononuclears. Constitutive (cNOS) and inducible (iNOS) activities were
      analyzed by the [3H]L-arginine-L-citrulline assay. Plasma NOx- was determined by
      chemiluminescence. NOx- was higher in septic vs. controls (median 110, IQR 39-250
      vs. 23, 14-46 microM; p<0.05). cNOS in septic cells was unmeasurable. iNOS in
      septic neutrophils was higher (median 34.9, IQR 10.4-95.8 vs. controls 2.5, 0-2.7
      U; p<0.05) while iNOS in septic mononuclears was unaltered (median 16.4, IQR 9.1
      52.6 vs. controls 8.9, 5.9-20.3 U; p=0.240). CONCLUSIONS: Increased iNOS activity
      was found in circulating neutrophils of septic shock patients compared to healthy
      volunteers. Moreover, differential iNOS activity was evident in circulating
      neutrophils vs. mononuclears of patients with septic shock. Further
      investigations are warranted to confirm this differential iNOS activity and to
      explore its significance.

PMID- 15959763
TI  - Dexamethasone therapy and memory performance.

PMID- 15959764
TI  - Inducible nitric oxide synthase inhibition improves intestinal microcirculatory
      oxygenation and CO2 balance during endotoxemia in pigs.
AB  - OBJECTIVE: We examined whether selective inhibition of inducible nitric oxide
      synthase (iNOS) promotes intestinal microvascular oxygenation (microPO2) and CO2
      off-load after endotoxic shock. DESIGN AND SETTING: Prospective, controlled
      experimental study in a university animal research laboratory. SUBJECTS: 13
      domestic pigs. INTERVENTIONS: After baseline measurements shock was induced by 1
      microg kg-1 h-1 endotoxin until mean arterial pressure fell below 60 mmHg. After
      30 min in shock the animals were resuscitated with either fluid alone (control,
      n=6) or fluid and the iNOS inhibitor N-[3-(aminomethyl)benzyl]acetamidine
      hydrochloride (1400W, n=7). As final experimental intervention all animals
      received the nonselective NOS inhibitor L-NAME. MEASUREMENTS AND RESULTS:
      Systemic and regional hemodynamic and oxygenation parameters were measured at
      baseline, during endotoxemia and shock, hourly for 3 h of 1400W therapy, and 30
      min after the final L-NAME administration. microPO2 was assessed by the Pd
      porphyrin phosphorescence technique, and the arterial to intestinal PCO2 gap was
      determined by air tonometry. Endotoxemia and shock resulted in a decrease in
      ileal mucosal and serosal microPO2 and a rise in PCO2 gap. The combination of
      1400W and fluid resuscitation, but not fluid alone, normalized both the serosal
      microPO2 and the intestinal PCO2 gap. Administration of L-NAME decreased cardiac
      output and oxygen delivery and intestinal microPO2 and blood flow in both groups.
      CONCLUSIONS: Partial blockade of NO production by 1400W increased serosal
      microvascular oxygenation and decreased the intestinal CO2 gap. This findings are
      consistent with the idea that 1400W corrects pathological flow distribution and
      regional dysoxia within the intestinal wall following endotoxic shock.

PMID- 15959765
TI  - A new distractor with angle-scale for proximal tibia medial opening wedge
      osteotomy.
AB  - Lateral tibial plateau fractures or lateral cortex fractures may occur when
      performing medial opening wedge osteotomy. Some special tools have been described
      to prevent lateral tibial plateau or lateral cortex fracture during the medial
      separation of the osteotomy planes in medial opening wedge osteotomy. The author
      has developed a distractor with angle-scale to prevent such complications.
      Between December 2001 and April 2004, 40 opening wedge osteotomies stabilised
      with the plate with wedge were performed on 38 patients. The distraction of
      initial osteotomies in 25 knees was done with different techniques and there were
      three lateral tibial plateau fractures and nine lateral cortex fractures. The
      remaining, recently operated, 15 knees were treated with the aid of the above
      described angle-scale distractor to prevent lateral tibial plateau and lateral
      cortex fractures. There was no lateral tibial plateau fractures during the
      surgery when we used this instrument for the distraction of the osteotomy sites.
      A subsequent prospective study evaluated this new device.

PMID- 15959766
TI  - Clinical and radiological outcome of medial patellofemoral ligament
      reconstruction with a semitendinosus autograft for patella instability.
AB  - BACKGROUND: Recurrent patellar instability is a common problem after dislocation.
      The medial patellofemoral ligament (MPFL) contributes 40-80% of the total medial
      restraining forces. This study assessed the clinical and radiological outcome
      after a follow-up of 4 years after linear MPFL reconstruction using an
      ipsilateral Semitendinosus tendon autograft. STUDY DESIGN AND METHODS: 15 knees
      in 12 patients were examined with a mean of 47 months after linear reconstruction
      of the MPFL at a mean age of 30 years. 3 knees underwent previous surgery. 3
      patients had mild trochlear dysplasia grade I or II, according to the
      classification of Dejour. If preoperative tibial tuberosity-trochlear groove
      distance (TTTG) was more than 15 mm, patients underwent additional medialisation
      of the tibial tuberosity (n=8) creating a similar postoperative situation for all
      patients. All patients were available for a postoperative evaluation, which
      consisted of a subjective questionnaire, the Kujala score, and the recording of
      potential patellar redislocation and apprehension. Patellar height and tilt was
      measured on plain radiographs. Postoperative CT scans were performed in patients
      with an additional tibial tuberosity-transfer. RESULTS: Postoperatively, one
      patient reported on recurrent bilateral redislocation. Physical examination
      however revealed no findings. Three knees presented with persistent patellar
      apprehension. Thirteen knees had improved subjectively after surgery. The mean
      Kujala score improved significantly from 55.0 to 85.7 points. The patellar tilt
      decreased significantly from 11.3 degrees to 9.2 degrees. Four knees had patella
      alta preoperatively, but only two at the latest follow-up visit. Previous surgery
      or additional trochlear dysplasia had no influence on the clinical outcome.
      CONCLUSION: MPFL reconstruction improves clinical symptoms, reduces the patellar
      tilt substantially, and may correct patella alta. Additional mild trochlear
      dysplasia did not compromise the outcome; however, this fact needs further
      attention in a larger study group.

PMID- 15959767
TI  - Stabilizing effects of ankle bracing under a combination of inversion and axial
      compression loading.
AB  - The combined effects of bracing, axial compression and inversion rotation on the
      ankle-subtalar complexes were evaluated. Ex vivo tests under the load-controlled
      condition were performed on six cadaver ankle specimens using a six degree-of
      freedom fixture. Inversion rotation was measured while subjecting the ankle
      subtalar complex to a 2.5 N-m inversion moment and a combination of the testing
      variables (brace type, no brace, 178 N axial compression load, no compression
      load, 0 degrees and 20 degrees of plantar flexion) for a total of 16 tests per
      specimen. Three commercially available braces (two semirigid types and one lace
      up type) were evaluated. An axial compression load significantly decreased ankle
      subtalar motion in unbraced ankles for the tested inversion moment. The
      contribution of bracing to stabilization of the ankle was smaller in the axial
      loading condition than in the no axial loading condition. The semirigid braces
      had greater stabilizing effects in response to the inversion moment than the lace
      up brace. Stabilizing effects of bracing were significantly greater in 20 degrees
      of plantar flexion than in 0 degrees of plantar flexion. The most common
      mechanism for an ankle sprain injury is inversion rotation on a weight-bearing
      ankle. Therefore, we should not overestimate stabilizing effects of bracing from
      evaluations of bracing without axial compression loading.

PMID- 15959769
TI  - My memories of Professor Wilhelm Fresenius.

PMID- 15959768
TI  - One-milliliter wet-digestion for inductively coupled plasma mass spectrometry
      (ICP-MS): determination of platinum-DNA adducts in cells treated with
      platinum(II) complexes.
AB  - Platinum (Pt)-DNA adducts formed by the anti-tumor agent cisplatin are recognized
      by the DNA mismatch repair (MMR) system. To investigate the involvement of MMR
      proteins including hMLH1 in the removal of these adducts, we developed a mL-scale
      wet-digestion method for inductively coupled plasma mass spectrometry (ICP-MS).
      The detection limit was 0.01 ng mL(-1) Pt, which corresponded to 2 pg Pt/microg
      DNA when 10 microg of DNA was used. The mean relative errors were 5.4% or better
      for a dynamic range of 0.01-10 ng mL(-1) Pt. DNA (approximately 500 microg) had
      no matrix effect. To improve the accuracy, DNA preparations were treated with
      ribonuclease and the apparent reduction in the concentration of Pt was corrected
      using cellular DNA levels, which were determined with Hoechst 33258. No
      significant differences were observed, in terms of the formation of Pt-DNA
      adducts or their removal over 6 h, between hMLH1-deficient HCT116 cells, a human
      colorectal cancer cell line, and hMLH1-complemented HCT116+ch3 cells (n=5;
      P>0.05), indicating that the hMLH1-dependent DNA repair systems contribute to
      neither the formation nor the removal of the adducts at detectable levels. In
      addition, approximately 19% of the adducts were removed within 6 h in both cell
      lines. A time course analysis (~24 h) suggested that the removal of cisplatin
      generated Pt-DNA adducts follows first-order kinetics (t(1/2)=32 h). The amount
      of Pt-DNA adduct formed by oxaliplatin in 1 h was 56% (ratio of means) of that
      generated by an equimolar concentration of cisplatin in HCT116. The proposed
      procedure could be useful for determining Pt-DNA adducts formed by Pt(II)
      complexes.

PMID- 15959770
TI  - Determining PAHs and PCBs in aqueous samples: finding and evaluating sources of
      error.
AB  - This work describes the problems that occur during routine multi-step
      determinations of polyaromatic hydrocarbons (PAHs) and polychlorinated biphenyls
      (PCBs), which can be present at trace levels in water, and identifies sources of
      analyte losses at particular steps during the analytical procedure. PAH and PCB
      adsorption onto the walls of the container ranged from 0 to 70%. PAH and PCB
      recoveries of >70% were achieved during the LLE and SPE extraction steps. During
      the process of enriching the dichloromethane extract with PAHs and PCBs, based on
      the gentle evaporation of solvent, losses were <24% and <19%, respectively. Model
      experiments show that neither isolation of PAHs and PCBs (performed using either
      LLE or SPE) nor extract enrichment reduce the reliability of PAH and PCB
      determination. The steps that lead to the greatest loss of analyte are the ones
      that involve sampling, transport and storage of the water samples.

PMID- 15959771
TI  - Fast fingerprinting by MALDI-TOF mass spectrometry of urinary sediment
      glycosphingolipids in Fabry disease.
AB  - Fabry disease (FD) is an X-linked inborn error of glycosphingolipid (GSL)
      metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A, which
      results in high levels in lysosomes and biological fluids of
      globotriaosylceramide (Gb3) and digalactosylceramide (Ga2), also known as
      galabiosylceramide. We report here a detailed study of the molecular species of
      GSLs in urinary samples obtained from hemizygous and heterozygous patients by use
      of matrix-assisted laser desorption ionisation and tandem mass spectrometry
      (MALDI-MS-MS). Twenty-two and fifteen molecular species were identified in the
      globotriaosylceramide and digalabiosylceramide series, respectively. The major
      sphingoid base was sphingosine (d18:1), and dihydrosphingosine (C18:0) and
      sphingadienine (d18:2) were also present. The molecular profiles obtained by
      MALDI-TOF-MS enabled us to show significant differences between GSLs composition
      for young, adult or atypic hemizygote and heterozygote patients. Thus, MALDI-TOF
      MS and MS-MS proved a powerful tool for screening a population of patients with
      clinical signs suggestive of FD by direct and rapid GSL fingerprinting and
      identification, and for study of the biological processes occurring in
      glycosphingolipid accumulation.

PMID- 15959772
TI  - [Unilateral visual impairment in the presence of retinal hemorrhages in a 35-year
      old female patient].

PMID- 15959773
TI  - The influence of static magnetic fields on mechanosensitive ion channel activity
      in artificial liposomes.
AB  - The influence of static magnetic fields (SMFs) on the activity of recombinant
      mechanosensitive ion channels (the bacterial mechanosensitive ion channel of
      large conductance-MscL) following reconstitution into artificial liposomes has
      been investigated. Preliminary findings suggest that exposure to 80-mT SMFs does
      not induce spontaneous MscL activation in the absence of mechanical stimulation.
      However, SMFs do appear to influence the open probability and single channel
      kinetics of MscL exposed to negative pipette pressure. Typical responses include
      an overall reduction in channel activity or an increased likelihood of channels
      becoming "trapped open" in sub-conducting states following exposure to SMFs.
      There is a delay in the onset of this effect and it is maintained throughout
      exposure. Generally, channel activity showed slow or limited recovery following
      removal of the magnetic field and responses to the magnetic were often reduced or
      abolished upon subsequent exposures. Pre-exposure of the liposomes to SMFs
      resulted in reduced sensitivity of MscL to negative pipette pressure, with higher
      pressures required to activate the channels. Although the mechanisms of this
      effect are not clear, our initial observations appear to support previous work
      showing that the effects of SMFs on ion channels may be mediated by changes in
      membrane properties due to anisotropic diamagnetism of lipid molecules.

PMID- 15959774
TI  - Immune responses to p53 in patients with cancer: enrichment in tetramer+ p53
      peptide-specific T cells and regulatory T cells at tumor sites.
AB  - OBJECTIVE: A majority of human cancers, including head and neck cancer (HNC),
      "overexpress" p53. Although T cells specific for wild-type (wt) sequence p53
      peptides are detectable in the peripheral blood of patients with HNC, it is
      unknown whether such T cells accumulate in tumor-involved tissues. Also, the
      localization of "regulatory" T cells (Treg) to tumor sites in HNC has not been
      investigated to date. METHODS: Tumor infiltrating lymphocytes (TIL), tumor
      involved or non-involved lymph node lymphocytes (LNL) and peripheral blood
      mononuclear cells (PBMC) were obtained from 24 HLA-A2.1+ patients with HNC. Using
      tetramers and four-color flow cytometry, the frequency of Treg and CD3+CD8+ T
      cells specific for wt p53 epitopes as well as their functional attributes were
      determined. RESULTS: The CD3+CD8+ tetramer+ cell frequency was significantly
      higher (P<0.001) in TIL than autologous PBMC as was the percentage of CD4+CD25+ T
      cells (P<0.003). TIL were enriched in FOXp3+, GITR+ and CTLA-4+ Treg. CD8+ TIL
      had low Zeta expression and produced little IFN-gamma after ex vivo stimulation
      relative to autologous PBMC or PBMC from NC. CONCLUSIONS: Anti-wt p53 epitope
      specific T cells and Treg preferentially localize to tumor sites in patients with
      HNC. However, despite enrichment in tumor peptide-specific T cells, the effector
      cell population (CD3+CD8+) in TIL or PBMC was unresponsive to activation in the
      tumor microenvironment enriched in Treg.

PMID- 15959775
TI  - Survivorship of the Charnley Elite Plus cemented femoral stem.
AB  - We report the results of the Charnley Elite Plus femoral stem in multiple
      surgeons' hands at a minimum of 3 years after implantation. Over a 4-year period,
      244 patients underwent 268 primary hip arthroplasty procedures using this
      particular stem. Patients underwent postal and radiographic review at a mean of
      4.5 (3.0--6.8) years following their arthroplasty. There were five revision
      procedures for aseptic loosening (5/268; 1.9%). Radiological assessment revealed
      gross radiological failure in a further 12 femoral stems (12/208; 5.8%). In the
      best case scenario, using revision for aseptic loosening as the endpoint, the
      survivorship for this period was 98.1%. If radiographic failures are incorporated
      into this endpoint, survivorship is 93.1%. This failure rate at an early stage
      raises concerns as to the long-term survivorship of this prosthesis.

PMID- 15959776
TI  - Long-term results and arthropathy following the modified Bristow-Latarjet
      procedure.
AB  - The incidence of early osteoarthritis after the modified Bristow procedure has
      been the subject of several articles during the last decade. Recurrent
      dislocation, recurrent subluxation after surgery or the procedure itself have
      been suggested as the main causes of degenerative changes. We assessed 19
      patients who underwent the Bristow procedure for recurrent anterior dislocations
      of the shoulder retrospectively. Only one redislocation occurred in 20 shoulders
      (six women and 13 men) with an average follow-up of 7.7 years. All patients were
      satisfied and experienced improved stability. Three patients showed arthritic
      changes (two mild and one moderate), which, surprisingly, were also seen in the
      opposite shoulder. We therefore conclude that the occurrence of arthropathic
      changes after surgical stabilisation is based on multiple factors, with the
      initial dislocation playing a major role.

PMID- 15959777
TI  - Successful outcome with anagrelide in pregnancy.

PMID- 15959778
TI  - Phase I study of etoposide, cisplatin and irinotecan triplet in patients with
      advanced-stage small-cell lung cancer.
AB  - AIM: The irinotecan-cisplatin combination has emerged as a new standard for the
      treatment of advanced-stage small-cell lung cancer (AS-SCLC). To move forward we
      developed a 3-day regimen of cisplatin, etoposide and irinotecan. METHODS:
      Successive cohorts of AS-SCLC patients were treated with irinotecan administered
      as a single 1-h infusion in combination with fixed doses of cisplatin (20
      mg/m(2)) and etoposide (75 mg/m(2)), both given for three consecutive days (ECI
      regimen). Irinotecan dose was escalated from 60 mg/m(2) by 40-mg/m(2) increments.
      At mid-step between the maximum tolerated dose (MTD) and the previous dose level,
      patients were randomized for the day of administration of irinotecan (day 1 vs
      day 3). RESULTS: A total of 36 AS-SCLC patients received 166 courses of treatment
      at four dose levels. The MTD of irinotecan was 140 mg/m(2) (three dose-limiting
      toxicities, DLTs), and the recommended optimal dose (ROD) 120 mg/m(2) (two DLTs).
      DLTs were febrile neutropenia and grade 3 diarrhea. Other toxicities were mild.
      No difference in toxicity was seen between the two time schedules. A 77% (95% CI
      63.25-90.75%) response rate was recorded among 31 evaluable patients and the
      median survival was 12 months. CONCLUSIONS: The ECI regimen was well tolerated
      and showed considerable activity in patients with AS-SCLC. Phase II/III
      evaluation is ongoing.

PMID- 15959779
TI  - Effects on DNA and RNA after the administration of two different schedules of 5
      fluorouracil in colorectal cancer patients.
AB  - PURPOSE: 5-Fluorouracil (5-FU) has two major mechanisms by which it exerts its
      anticancer activity. One mechanism operates through the inhibition of thymidylate
      synthetase (TS) by the active metabolite 5-fluorodeoxyuridine 5'-monophosphate.
      The other mechanism is the incorporation of 5-FU into RNA. Using tumor tissue
      specimens from colon carcinoma patients given 5-FU by two different modes of
      administration, we investigated the effects of 5-FU on DNA and RNA. EXPERIMENTAL
      DESIGN: Group A patients received 200 mg/day of 5-FU as a rapid infusion for 5
      days preoperatively, and group B patients received 200 mg/day of 5-FU as a
      continuous infusion for 5 days preoperatively. Postoperatively, we analyzed the 5
      FU concentration, 5-FU incorporation into RNA (F-RNA), and TS inhibition rate
      (TSIR) in normal tissue, cancerous tissue, and lymph nodes. RESULTS: The F-RNA
      concentration in tumor tissue from group A patients was higher than in tissue
      from group B patients. The TS concentrations in tumor tissue were significantly
      higher than in non-tumor tissue in both groups. In lymph nodes, the TSIR of group
      A was 78.5% and that of group B was 55.2%, a significant difference. CONCLUSION:
      Bolus injection can be considered to be more effective with respect to RNA damage
      in tumor tissue. Especially in cases involving lymph node metastasis, bolus
      injection was effective with respect to DNA damage as well as RNA damage.

PMID- 15959780
TI  - Hyperacetylation enhances the growth-inhibitory effect of all-trans retinoic acid
      by the restoration of retinoic acid receptor beta expression in head and neck
      squamous carcinoma (HNSCC) cells.
AB  - The chemotherapeutic effects of all-trans-retinoic acid (atRA) are mediated by
      the retinoic acid receptor beta (RARbeta), but RARbeta expression is reduced in a
      number of head and neck carcinoma (HNSCC) cells which causes resistance to RA
      treatment in half the patients with HNSCC. The possible mechanism for the reduced
      RARbeta expression has been suggested as the methylation of the CpG islands
      adjacent to the RA response elements (RARE) in the RARbeta promoter and the loss
      of histone acetylation. The suppressed RARbeta expression can be reactivated by a
      demethylating agent (5-aza-2'-deoxycytidine, 5-AzaC) or a histone deacetylase
      inhibitor (trichostatin A, TSA). Therefore, we sought to determine if the
      restoration of RARbeta activity, or a combination of these drugs, could restore
      the sensitivity to RA in RARbeta-negative HNSCC cells with an epigenetically
      methylated RARbeta promoter region. SqCC/Y1 cells resistant to atRA showed
      methylated and unmethylated forms in the RARbeta promoter region. RARbeta
      expression of these cells was restored by 5-AzaC or TSA treatment. Also,
      treatment with TSA and atRA combined synergistically increased the growth
      inhibitory effect and highly induced the transcriptional activation of the
      RARbeta promoter compared to atRA treatment in HNSCC cells. Additionally, TSA
      alone and the combination 5-AzaC and TSA increased lysine-9 (Lys-9) acetylation
      and Lys-4 methylation of the first exon at the RARbeta gene, while decreasing the
      methylation of Lys-9 in the HNSCC cells.

PMID- 15959783
TI  - [Zygomycetes in biopsies of the gastrointestinal tract].
AB  - Zygomycosis (Mucor- and Entomophtoramycosis) of the gastrointestinal tract is
      rare compared to other mycoses in the gastrointestinal area. The infection occurs
      mainly in immunosuppressed patients but rare cases concerning immunocompetent
      persons are also documented. Zygomycosis occurs in the gastrointestine primarily
      or due to disseminated disease. We report on a 48-year-old female alcohol
      addicted patient who underwent gastric biopsies. The biopsy results showed
      invasive zygomycosis. Shortly thereafter, the patient died of sepsis. The second
      case presented here is a 15-year-old female patient with recurrent vomiting.
      Histological and immunohistochemical analysis of duodenal biopsy specimens
      revealed fungi of the class Zygomycetes. In addition, histological and/or
      microbiological examination demonstrated the presence of Candida in both
      cases.Zygomycosis of the gastrointestinal tract can have an aggressive course,
      making it important to know the morphological characteristics of the disease to
      facilitate early diagnosis and therapy. This is all the more important because
      the cultivation of fungi, as in our cases, is not always successful.

PMID- 15959781
TI  - Role of helminths in regulating mucosal inflammation.
AB  - The rapid rise in prevalence of ulcerative colitis (UC) and Crohn's disease (CD)
      in highly developed countries suggests that environmental change engenders risk
      for inflammatory bowel disease (IBD). Eradication of parasitic worms (helminths)
      through increased hygiene may be one such change that has led to increased
      prevalence of these diseases. Helminths alter host mucosal and systemic immunity,
      inhibiting dysregulated inflammatory responses. Animals exposed to helminths are
      protected from experimental colitis, encephalitis, and diabetes. Patients with CD
      or UC improve when exposed to whipworm. Lamina propria (LP) mononuclear cells
      from helminth-colonized mice make less interleukin (IL)-12 p40 and IFN-gamma, but
      more IL-4, IL-13, IL-10, TGF-beta, and PGE(2) compared to LP mononuclear cells
      from naive mice. Systemic immune responses show similar skewing toward Th2 and
      regulatory cytokine production in worm-colonized animal models and humans. Recent
      reports suggest that helminths induce regulatory T cell activity. These effects
      by once ubiquitous organisms may have protected individuals from many of the
      emerging immune-mediated illnesses like IBD, multiple sclerosis, type I diabetes,
      and asthma.

PMID- 15959782
TI  - The role of mucosal T lymphocytes in regulating intestinal inflammation.
AB  - Suppression of chronic intestinal inflammation by different subtypes of T cells
      has been described in recent years. In particular, naturally arising
      CD4(+)CD25(+) regulatory T cells and IL-10-producing regulatory T cell type 1
      CD4(+) T lymphocytes have been implicated in the regulation of intestinal
      inflammation. Here we focus on the ability of CD4(+)CD25(+) regulatory T cells to
      suppress innate and T-cell responses and discuss implications for
      immunoregulation in human inflammatory bowel disease. Besides the modulation of
      lymphoproliferation, a role for CD4(+)CD25(+) T cells in down-modulation of
      innate immune responses is emerging and the immunoregulatory activities of
      regulatory T cells in vivo may be mediated via effects on dendritic cells.
      Considering the extraordinary regenerative potential of the intestinal mucosa,
      the ability to impede pathogenic T-cell responses by active regulation might be
      of particular therapeutic benefit for the treatment of chronic intestinal
      inflammatory diseases such as Crohn's disease and ulcerative colitis.

PMID- 15959784
TI  - A prospective randomised controlled clinical trial comparing the efficacy of
      different molecular weight hyaluronan solutions in the treatment of knee
      osteoarthritis.
AB  - Viscosupplementation consists of injecting exagenous hyaluronan (HA) into the
      synovial joints to restore the normal rheological environment which deteriorates
      severely in osteoarthritic (OA) joints. Efficacy might be related to the
      rheological properties and molecular weight (MW) of the hyaluronan preparations.
      This prospective, controlled, double-blind, randomised clinical trial was aimed
      at comparing the elastoviscous properties of a high molecular weight
      viscosupplement, hylan G-F 20, with that of a lower molecular weight hyaluronan
      product in order to determine the relationship of elastoviscosity to efficacy,
      alongside placebo, in the treatment of patients with knee OA. The results were
      analysed as a "completers" analysis with 59 patients. Primary outcome measures
      included the Western Ontario and Mc Master Universities' Osteoarthritis Index
      (WOMAC) for pain, stiffness and function scores, and patient and physician global
      assessments (0-100 scale). For patient (PGA) and physician global assessments
      (PhGA), the 0-100 scale was used, with 100 being the worst. Follow-up assessments
      were made at intervals of 1, 3 and 6 months after the first injection. Local
      adverse events, such as transient pain at the injection site or warm knee lasting
      for one night, were recorded in two patients (3%). In all groups, the WOMAC pain
      score exhibited a significant difference from the baseline value; neither
      treatment group was significantly different from the placebo group, but total
      pain score was significantly better than baseline for both of the HA groups at
      the end of 6 months (p < 0.05). Improvement in WOMAC physical function score
      favoured both sodium hyaluronate and hylan G-F 20 after the first month, and
      remained significant until the end of 6 months (p < 0.01). In the placebo group,
      the physical function scores became worse after the end of the 1st month; the
      scores at the end of 6 months were no different from those at the beginning. The
      WOMAC stiffness scores of both of the hyaluronic acid groups improved with the
      first injection, and remained significantly better than the placebo group until
      the end of the survey (p < 0.001). All groups expressed improvement with PGA
      scores after the first injection. At the end of 6 months all three groups were
      similar, but the treatment groups were significantly better than the placebo
      group (p < 0.05), and all were significantly better than at the beginning (p <
      0.05). The PhGA scores were similar in all groups until after the third
      injection. The second group was slightly better in the controls at 1 and 3
      months, but all the groups were similar at the end of 6 months. Although the
      placebo group seemed worse, it was not statistically significant. Compared with
      lower molecular weight HA, the higher molecular weight HA might be more
      efficacious in treating knee OA, but heterogeneity of previous studies limited
      definitive conclusions. Patients treated by injection of either of two hyaluronan
      preparations showed clinical improvement for pain, though no different from the
      placebo group; WOMAC stiffness scores were better than placebo in the HA groups,
      whereas PGA scores showed improvement in all groups but HA groups were better
      than placebo. PhGA scores were worse in the placebo group, but not to a
      statistically-significant extent. The HA groups did not differ in terms of
      clinical efficacy.

PMID- 15959785
TI  - Non-Hodgkin's lymphoma among the gamut of differential diagnoses for shoulder
      pain.

PMID- 15959786
TI  - Urinary calculi: improved detection and characterization with thin-slice
      multidetector CT.
AB  - The aim of this study was to assess the effect of reconstructed slice thickness
      on the detection and characterization of human urinary calculi on a multidetector
      helical CT scanner. Nineteen human urinary calculi of various chemical
      composition measuring 1.0-3.7 mm were embedded into agar in a chamber of a nylon
      body phantom. The phantom was imaged with a four detector-row CT scanner. The
      number of detected calculi increased as the reconstructed slice thickness
      decreased. Measured diameters and density of the visible calculi decreased as the
      slice thickness increased. The results of the present study support the use of
      thin reconstructed slices to detect and characterize urinary calculi.

PMID- 15959787
TI  - Spontaneous rupture of the distal iliopsoas tendon: clinical and imaging
      findings, with anatomic correlations.
AB  - We report the clinical and imaging findings in two elderly female patients with
      spontaneous rupture of the distal iliopsoas tendon from the lesser trochanter of
      the femur. We emphasize the key contribution of magnetic resonance (MR) imaging
      to this diagnosis and provide an anatomic correlation. Spontaneous rupture of the
      distal iliopsoas tendon should be kept in mind in the differential diagnosis of
      acute groin pain in the elderly. MR imaging enables positive diagnosis, by
      showing mass effect on the anterior aspect of the hip joint, proximal muscle
      thickening, and abnormal signal intensity, and by demonstrating interruption of
      the psoas tendon, whereas the distal insertion of the lateral portion of the
      iliacus muscle remains muscular and is preserved.

PMID- 15959788
TI  - Osteonecrosis induced by intraoperative radiotherapy for pancreatic cancer.

PMID- 15959791
TI  - Early results of a rotational flap to treat chronic anal fissures.
AB  - BACKGROUND: Treatment of anal fissures has changed dramatically in the past
      decade. Only a few fail to respond to medical therapy. Sphincterotomy and anal
      dilatation have fallen out of favour due to the risk of incontinence. Island
      flaps have been proposed to address this, but 60--70% of flap donor sites break
      down with complications. We proposed that using a rotational flap would overcome
      this problem. METHODS: Twenty-one patients (14 women,7 men) with chronic anal
      fissures were treated with rotation flap from perianal skin. The median age was
      43 (range 21--76) years. All patients had failed chemical sphincterotomy and
      showed no signs of improvement following at least a 3-month course of topical GTN
      0.2% ointment. RESULTS: The median hospital stay was 2 days. Seventeen patients
      had complete resolution of symptoms. Only one patient continued to have severe
      pain. Two developed a recurrent fissure. One patient had a combined fistula
      fissure complex at diagnosis and suffered from a breakdown of the flap and donor
      site. Another patient had had haemorrhoidectomy and an advancement flap in the
      past. He developed problems with the donor site, which was successfully managed
      conservatively. One patient had persistent mild pain after surgery, but the cause
      could not be found. None of the patients suffered continence defects after
      surgery. CONCLUSION: Use of a rotational flap is a simple, safe and successful
      treatment for anal fissures. Donor site problems are minimised using this
      approach. It should be a treatment of choice when surgery is required for chronic
      anal fissures, particularly in patients in whom there is a risk of incontinence.

PMID- 15959792
TI  - Epithelioid hemangiosarcoma of the rectum.

PMID- 15959790
TI  - The insulin-like growth factor system and colorectal cancer: clinical and
      experimental evidence.
AB  - OBJECTIVE: The aim of this review is to clarify the involvement of the insulin
      like growth factor (IGF) system in the development of colorectal malignancy.
      MATERIALS AND METHODS: Medline searches were used to identify key articles
      relating the IGF system with the development of colorectal cancer. RESULTS: The
      IGF system has been linked to colorectal malignancy by a convergence of data from
      epidemiological, clinical and laboratory-based sources. CONCLUSION: Further work
      is needed to characterise the IGF system expression in the colon. Such
      clarification could lead to the identification of targets that can be manipulated
      for clinical advantage.

PMID- 15959793
TI  - Management of sacrococcygeal chordoma mimicking a pilonidal sinus: report of a
      case.

PMID- 15959794
TI  - Cerebellopontine calcification: a new entity of idiopathic intracranial
      calcification?
AB  - We report the autopsy case of a 40-year-old woman with severe intellectual and
      motor disabilities, who showed calcification in the cerebellum and pons but not
      in the basal ganglia on CT scan, and died of intracranial hemorrhage due to
      intractable hypertension. At autopsy, numerous calcium deposits were noted in the
      cerebellar cortex, the dentate nucleus, the cerebellar white matter and the
      ventral pons. These deposits were distributed both in the neuropil and the white
      matter, but rarely within the arterial walls or in contact with capillaries. This
      weak relationship between calcification and the blood vessels, in addition to the
      paucity of basal ganglia calcification, is in contrast to the findings with other
      disorders involving intracranial calcification, including Fahr's disease and
      calcium metabolism disorders. Immunohistochemistry revealed intense staining of
      calbindin-D28K and parvalbumin at sites of calcium deposits both in the present
      case and in a case of pseudohypoparathyroidism, whereas these proteins were not
      localized to calcium deposits in the cerebellum of a Fahr's disease brain. We
      propose that the present case may represent a distinct entity among diseases
      characterized by idiopathic intracranial calcification. In addition, calcium
      binding proteins may be involved in the calcification process in some cases with
      intracranial calcification.

PMID- 15959795
TI  - Intracranial abscesses associated with chronic suppurative otitis media.
AB  - Intracranial abscesses are serious complications of chronic suppurative otitis
      media (COM). This study included 32 patients presenting with intracranial
      abscesses from 780 patients hospitalized for treatment of COM. The 32 patients
      had 59 intracranial complications. Perisinus abscess (13 of 32) was the most
      common intracranial abscess, followed by temporal lobe abscess (8 of 32),
      epidural abscess (7 of 32), cerebellar abscess (6 of 32) and subdural empyema (2
      of 32). Headache (93%), fever (87%) and altered mental status (62%) were the most
      common presenting symptoms and signs, along with symptoms of COM. All patients
      were treated with intravenous antibiotics and canal wall down mastoidectomy.
      Cholesteatoma with granulation tissue and bony defects at the sinus plate and/or
      dural plate were seen in most of the patients. Gram negative bacilli and
      anaerobes were the most common organisms cultured from the abscesses. Three
      patients had neurological sequels. One patient died. The early diagnosis of these
      complications requires a high index of suspicion and imaging studies. A
      multidisciplinary and coordinated approach is important for the management of
      these patients.

PMID- 15959796
TI  - Immunohistochemical distribution of activated nuclear factor kappaB and
      peroxisome proliferator-activated receptors in carbon tetrachloride-induced
      chronic liver injury in rats.
AB  - We investigated the immunohistochemical distribution of active NF-kappaB p65 and
      peroxisome proliferator-activated receptor (PPAR) subtypes alpha and gamma in the
      different phases of liver steatonecrosis and cirrhosis induced in rats after 3
      and 9 weeks of carbon tetrachloride (CCl4) intoxication. CCl4 treatment can
      induce changes in the expression of NF-kappaB and PPARs. Immunohistochemical
      analysis of liver tissue sections from rats with steatonecrosis or cirrhosis
      demonstrated a significant increase in the number of NF-kappaB-positive and TNF
      alpha-positive hepatocytes and Kupffer cells. In healthy controls, no expression
      of active NF-kappaB was detected. In previous studies, we have demonstrated that
      Kupffer cells isolated from rats with CCl4-induced steatonecrosis produced more
      reactive oxygen intermediates than cells isolated from normal rats. These
      oxidants could activate NF-kappaB and lead to an overexpression of TNF-alpha,
      observed in liver tissue sections. After CCl4 ingestion, the rat livers
      demonstrated a significantly decreased number of hepatocytes expressing PPARalpha
      and PPARgamma and a significantly increased number of ED2-positive Kupffer cells
      expressing these transcription factors, compared to normal. The activation of the
      p65 isoform of NF-kappaB correlates negatively with transcription of the alpha
      and gamma isoforms of PPAR in hepatocytes, and positively in Kupffer cells. These
      results suggest that the regulation and the role of these two transcription
      factors differ in the two cell types studied.

PMID- 15959797
TI  - 70 microM caffeine treatment enhances in vitro force and power output during
      cyclic activities in mouse extensor digitorum longus muscle.
AB  - Caffeine ingestion by human athletes has been found to improve endurance
      performance primarily acting via the central nervous system as an adenosine
      receptor antagonist. However, a few studies have implied that the resultant
      micromolar levels of caffeine in blood plasma (70 microM maximum for humans) may
      directly affect skeletal muscle causing enhanced force production. In the present
      study, the effects of 70 microM caffeine on force and power output in isolated
      mouse extensor digitorum longus muscle were investigated in vitro at 35 degrees
      C. Muscle preparations were subjected to cyclical sinusoidal length changes with
      electrical stimulation conditions optimised to produce maximal work. 70 microM
      caffeine caused a small but significant increase (2-3%) in peak force and net
      work produced during work loops (where net work represents the work input
      required to lengthen the muscle subtracted from the work produced during
      shortening). However, these micromolar caffeine levels did not affect the overall
      pattern of fatigue or the pattern of recovery from fatigue. Our results suggest
      that the plasma concentrations found when caffeine is used to enhance athletic
      performance in human athletes might directly enhance force and power during brief
      but not prolonged activities. These findings potentially confirm previous in vivo
      studies, using humans, which implied caffeine ingestion may cause acute
      improvements in muscle force and power output but would not enhance endurance.

PMID- 15959798
TI  - Hemodynamic and hormonal responses to a short-term low-intensity resistance
      exercise with the reduction of muscle blood flow.
AB  - We investigated the hemodynamic and hormonal responses to a short-term low
      intensity resistance exercise (STLIRE) with the reduction of muscle blood flow.
      Eleven untrained men performed bilateral leg extension exercise under the
      reduction of muscle blood flow of the proximal end of both legs pressure-applied
      by a specially designed belt (a banding pressure of 1.3 times higher than resting
      systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE
      was 20% of one repetition maximum. The subjects performed 30 repetitions, and
      after a 20-seconds rest, they performed three sets again until exhaustion. The
      superficial femoral arterial blood flow and hemodynamic parameters were measured
      by using the ultrasound and impedance cardiography. Serum concentrations of
      growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline
      (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also
      measured. Under the conditions with Kaatsu, the arterial flow was reduced to
      about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/
      0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01),
      and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to
      neither NE nor lactate, but the increase in VEGF was related to that in lactate
      (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal
      heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than
      that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the
      venous return by Kaatsu, but, total peripheral resistance (TPR) did not change
      significantly. These results suggest that STLIRE with Kaatsu significantly
      stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of
      cardiac preload during exercise, which may become a unique method for
      rehabilitation in patients with cardiovascular diseases.

PMID- 15959799
TI  - Limb vasodilatory capacity and venous capacitance of trained runners and
      untrained males.
AB  - Aerobically trained athletes possess enhanced vasodilatory capacity and venous
      capacitance in their exercising muscles. However, whether they also possess these
      characteristics in their non-specific exercising muscles is undetermined. This
      study examined vasodilatory capacity and venous capacitance of specific (legs)
      and non-specific exercising muscles (arms) of ten trained runners and ten active
      but untrained males aged 18-35 years. Venous occlusion plethysmography determined
      baseline and peak blood flow after 5 min of reactive hyperaemia. Forearm and leg
      venous capacitance were determined as the difference between baseline and 2 min
      of venous occlusion at 50 mmHg. During reactive hyperaemia, trained runners had
      higher leg (48.4+/-5.3 ml.100 ml tissue(-1).min(-1)) and arm (40.8+/-2.1 ml.100
      ml tissue(-1).min(-1)) vasodilatory capacity compared to the untrained (leg:
      37.3+/-2.5 ml.100 ml tissue(-1).min(-1); arm: 34.2+/-2.2 ml.100 ml tissue(
      1).min(-1); P<0.05), and higher calf vascular conductance (0.51+/-0.06 ml.100 ml
      tissue(-1).min(-1).mmHg(-1) versus 0.35+/-0.03 ml.100 ml tissue(-1).min(-1).mmHg(
      1); P<0.05). The trained also had higher venous capacitance in both arms (3.5+/
      0.2 ml 100.ml(-1)) and legs (4.8+/-0.1 ml.100 ml(-1)) compared to the untrained
      (3.0+/-0.2 ml 100.ml(-1); 4.2+/-0.2 ml.100 ml(-1); P<0.05). These findings show
      that vasculature adaptations to running occur in both specific and non-specific
      exercising muscles.

PMID- 15959800
TI  - Inverse relationship between exercise economy and oxidative capacity in muscle.
AB  - An inverse relationship has been shown between running and cycling exercise
      economy and maximum oxygen uptake (VO2max). The purposes were: 1) determine the
      relationship between walking economy and VO2max; and 2) determine the
      relationship between muscle metabolic economy and muscle oxidative capacity and
      fiber type. Subjects were 77 premenopausal normal weight women. Walking economy
      (1/VO2max) was measured at 3 mph and VO2max during graded treadmill test. Muscle
      oxidative phosphorylation rate (OxPhos), and muscle metabolic economy (force/ATP)
      were measured in calf muscle using 31P MRS during isometric plantar flexion at 70
      and 100% of maximum force, (HI) and (MI) respectively. Muscle fiber type and
      citrate synthase activity were determined in the lateral gastrocnemius.
      Significant inverse relationships (r from -0.28 to -0.74) were observed between
      oxidative metabolism measures and exercise economy (walking and muscle). Type IIa
      fiber distribution was inversely related to all measures of exercise economy (r
      from -0.51 to -0.64) and citrate synthase activity was inversely related to
      muscle metabolic economy at MI (r = -0.56). In addition, Type IIa fiber
      distribution and citrate synthase activity were positively related to VO2max and
      muscle OxPhos at HI and MI (r from 0.49 to 0.70). Type I fiber distribution was
      not related to any measure of exercise economy or oxidative capacity. Our results
      support the concept that exercise economy and oxidative capacity are inversely
      related. We have demonstrated this inverse relationship in women both by indirect
      calorimetry during walking and in muscle tissue by 31P MRS.

PMID- 15959801
TI  - Comparison between maximal power in the power-endurance relationship and maximal
      instantaneous power.
AB  - The purpose of this study was to analyze the relevance of introducing the maximal
      power (P(m)) into a critical-power model. The aims were to compare the P(m) with
      the instantaneous maximal power (P(max)) and to determine how the P(m) affected
      other model parameters: the critical power ( P(c)) and a constant amount of work
      performed over P(c)(W'). Twelve subjects [22.9 (1.6) years, 179 (7) cm, 74.1
      (8.9) kg, 49.4 (3.6) ml/min/kg] completed one 15 W/min ramp test to assess their
      ventilatory threshold (VT), five or six constant-power to exhaustion tests with
      one to measure the maximal accumulated oxygen deficit (MAOD), and six 5-s all-out
      friction-loaded tests to measure P(max) at 75 rpm, which was the pedaling
      frequency during tests. The power and time to exhaustion values were fitted to a
      2-parameter hyperbolic model (NLin-2), a 3-parameter hyperbolic model (NLin-3)
      and a 3-parameter exponential model (EXP). The P(m) values from NLin-3 [760 (702)
      W] and EXP [431 (106) W] were not significantly correlated with the P(max) at 75
      rpm [876 (82) W]. The P(c) value estimated from NLin-3 [186 (47) W] was not
      significantly correlated with the power at VT [225 (32) W], contrary to other
      models ( P <0.001). The W' from NLin-2 [25.7 (5.7) kJ] was greater than the MAOD
      [14.3 (2.7) kJ, P < 0.001] with a significant correlation between them (R = 0.76,
      P <0.01). For NLin-3, computation of W (P > P c), the amount of work done over
      P(C), yielded results similar to the W' value from NLin-2: 27.8 (7.4) kJ, which
      correlated significantly with the MAOD (R = 0.72, P <0.01). In conclusion, the
      P(m) was not related to the maximal instantaneous power and did not improve the
      correlations between other model parameters and physiological variables.

PMID- 15959802
TI  - An unusual cause of stridor in childhood due to focal epileptic seizures.
AB  - Respiratory disorders with stridor are a frequent cause of admission for children
      in an emergency department. Laryngospasm, as an isolated symptom of epilepsy, is
      a rare phenomenon [1, 3, 5]. Other respiratory symptoms of epilepsy, rarely seen
      in childhood, might be apnoeic spells [2, 4]. We report on a child with
      laryngospasm due to focal epileptic seizures.

PMID- 15959803
TI  - Cryptococcal meningitis in an immunocompetent child.

PMID- 15959804
TI  - Transmission electron microscopy of the scolex and neck microtriches of
      Silurotaenia siluri (Batsch, 1786) (Cestoda: Proteocephalidea).
AB  - Microtriches on different parts of the scolex and neck of the gangesiine cestode
      Silurotaenia siluri (Batsch 1786) were studied. The neodermis of the central
      frontal scolex part (around the rostellar furrow) bears filamentous microtriches
      only. The lateral frontal part and the parts between and posterior to the suckers
      cover filamentous and spine-like microtriches. Within the suckers there are short
      spine-like microtriches with bases enforced by electron-dense ribs. The proximal
      neck part bears filamentous and spine-like microtriches, the middle part solitary
      distributed blade-like and spine-like microtriches among filamentous ones, and
      the distal part blade-like microtriches. The functions of different types of
      microtriches are discussed.

PMID- 15959805
TI  - The role of alternative translation start sites in the generation of human
      protein diversity.
AB  - According to the scanning model, 40S ribosomal subunits initiate translation at
      the first (5' proximal) AUG codon they encounter. However, if the first AUG is in
      a suboptimal context, it may not be recognized, and translation can then initiate
      at downstream AUG(s). In this way, a single RNA can produce several variant
      products. Earlier experiments suggested that some of these additional protein
      variants might be functionally important. We have analysed human mRNAs that have
      AUG triplets in 5' untranslated regions and mRNAs in which the annotated
      translational start codon is located in a suboptimal context. It was found that
      3% of human mRNAs have the potential to encode N-terminally extended variants of
      the annotated proteins and 12% could code for N-truncated variants. The predicted
      subcellular localizations of these protein variants were compared: 31% of the N
      extended proteins and 30% of the N-truncated proteins were predicted to localize
      to subcellular compartments that differed from those targeted by the annotated
      protein forms. These results suggest that additional AUGs may frequently be
      exploited for the synthesis of proteins that possess novel functional properties.

PMID- 15959806
TI  - Upstream stimulatory factor 1 associated with familial combined hyperlipidemia,
      LDL cholesterol, and triglycerides.
AB  - Positive evidence has been reported for linkage and association between the
      upstream stimulatory factor 1 gene (USF1) and familial combined hyperlipidemia
      (FCHL). We genotyped the two most positive single-nucleotide polymorphisms (SNPs)
      (usf1s1: rs3737787 and usf1s2: rs2073658) from previous studies in a large family
      sample. This sample included 2,195 subjects in 87 Utah pedigrees ascertained for
      early death due to coronary heart disease (CHD), early strokes, or early onset
      hypertension. There were a total of 262 relative pairs in these families with
      FCHL. In the full family sample, FCHL was associated with usf1s1 (P = 0.02).
      Triglyceride and LDL cholesterol defined qualitatively or quantitatively were
      also associated with usf1s1 (P = 0.02-0.05). Results were strengthened for
      qualitative and quantitative triglyceride and LDL cholesterol when data from
      males only was analyzed, revealing associations for usf1s1 (P = 0.001-0.02),
      usf1s2 (P = 0.02-0.05) and the haplotype of these two SNPs (P = 0.01-0.04). The
      strongest results were in the subset of subjects from families ascertained for
      premature stroke or hypertension, rather than those ascertained for premature
      CHD. This study replicates the involvement of USF1 in FCHL and related lipid
      traits in a family sample not ascertained for FCHL.

PMID- 15959807
TI  - Genome scan for quantitative trait loci influencing HDL levels: evidence for
      multilocus inheritance in familial combined hyperlipidemia.
AB  - Several genome scans in search of high-density lipoprotein (HDL) quantitative
      trait loci (QTLs) have been performed. However, to date the actual identification
      of genes implicated in the regulation of common forms of HDL abnormalities
      remains unsuccessful. This may be due, in part, to the oligogenic and
      multivariate nature of HDL regulation, and potentially, pleiotropy affecting HDL
      and other lipid-related traits. Using a Bayesian Markov Chain Monte Carlo (MCMC)
      approach, we recently provided evidence of linkage of HDL level variation to the
      APOA1-C3-A4-A5 gene complex, in familial combined hyperlipidemia pedigrees, with
      an estimated number of two to three large QTLs remaining to be identified. We
      also presented results consistent with pleiotropy affecting HDL and triglycerides
      at the APOA1-C3-A4-A5 gene complex. Here we use the same MCMC analytic strategy,
      which allows for oligogenic trait models, as well as simultaneous incorporation
      of covariates, in the context of multipoint analysis. We now present results from
      a genome scan in search for the additional HDL QTLs in these pedigrees. We
      provide evidence of linkage for additional HDL QTLs on chromosomes 3p14 and
      13q32, with results on chromosome 3 further supported by maximum parametric and
      variance component LOD scores of 3.0 and 2.6, respectively. Weaker evidence of
      linkage was also obtained for 7q32, 12q12, 14q31-32 and 16q23-24.

PMID- 15959809
TI  - Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q
      and germline HSF4 mutations.
AB  - Isolated (non-syndromic) congenital cataract may be inherited as an autosomal
      dominant, autosomal recessive, or X-linked recessive trait. Considerable progress
      has been made in identifying genes and loci for dominantly inherited cataract,
      but the molecular basis for autosomal recessive disease is less well defined.
      Hence we undertook genetic linkage studies in four consanguineous Pakistani
      families with non-syndromic autosomal recessive congenital cataracts. In two
      families linkage to a 38 cM region 9q13-q22 was detected. Although a locus for
      recessive congenital cataracts had not been mapped previously to this region, the
      target interval encompasses the candidate region autosomal recessive adult-onset
      pulverulent cataracts (CAAR). The CAAR was mapped previously to 9q13-q22, and may
      therefore be allelic to non-syndromic autosomal recessive congenital cataracts.
      The other two families did not demonstrate linkage to 9q, but both had a region
      of homozygosity at 16q22 containing the heat shock transcription factor 4 (HSF4)
      gene. The HSF4 mutations have been reported in four families with autosomal
      dominant cataracts and, recently, in a single kindred with autosomal recessive
      congenital cataract. Mutation analysis of HSF4 revealed homozygous mutations
      (p.Arg175Pro and c.595_599delGGGCC, respectively) in the two families. These
      findings confirm that mutations in HSF4 may result in both autosomal dominant and
      autosomal recessive congenital cataract, and highlight the locus heterogeneity in
      autosomal recessive congenital cataract.

PMID- 15959808
TI  - Significant genetic differentiation between Poland and Germany follows present
      day political borders, as revealed by Y-chromosome analysis.
AB  - To test for human population substructure and to investigate human population
      history we have analysed Y-chromosome diversity using seven microsatellites (Y
      STRs) and ten binary markers (Y-SNPs) in samples from eight regionally
      distributed populations from Poland (n = 913) and 11 from Germany (n = 1,215).
      Based on data from both Y-chromosome marker systems, which we found to be highly
      correlated (r = 0.96), and using spatial analysis of the molecular variance
      (SAMOVA), we revealed statistically significant support for two groups of
      populations: (1) all Polish populations and (2) all German populations. By means
      of analysis of the molecular variance (AMOVA) we observed a large and
      statistically significant proportion of 14% (for Y-SNPs) and 15% (for Y-STRs) of
      the respective total genetic variation being explained between both countries.
      The same population differentiation was detected using Monmonier's algorithm,
      with a resulting genetic border between Poland and Germany that closely resembles
      the course of the political border between both countries. The observed genetic
      differentiation was mainly, but not exclusively, due to the frequency
      distribution of two Y-SNP haplogroups and their associated Y-STR haplotypes:
      R1a1*, most frequent in Poland, and R1*(xR1a1), most frequent in Germany. We
      suggest here that the pronounced population differentiation between the two
      geographically neighbouring countries, Poland and Germany, is the consequence of
      very recent events in human population history, namely the forced human
      resettlement of many millions of Germans and Poles during and, especially,
      shortly after World War II. In addition, our findings have consequences for the
      forensic application of Y-chromosome markers, strongly supporting the
      implementation of population substructure into forensic Y chromosome databases,
      and also for genetic association studies.

PMID- 15959810
TI  - Neuroanatomical, immunocytochemical, and physiological studies of the pharyngeal
      retractor muscle and its putative regulatory neurons playing a role in withdrawal
      and feeding in the snail, Helix pomatia.
AB  - We describe the neurons regulating two separate functions of the pharyngeal
      retractor muscle (PRM), namely sustained contraction during body withdrawal and
      rhythmic phasic contractions during feeding, in the snail, Helix pomatia. The
      distribution of central neurons innervating the PRM is organized into two main
      units; one in the buccal-cerebral ganglion complex, the other in the
      subesophageal ganglion complex. Serotonin- (5-HT-), FMRFamide- (FMRFa-), and
      tyrosine-hydroxylase-immunostained neurons are present among the PRM neurons that
      densely innervate the PRM. 5HT both decreases and increases the amplitude of the
      electrically evoked contraction between concentrations of 0.1 microM and 1
      microM. Dopamine (DA) only decreases the amplitude of contraction at a 1-microM
      threshold concentration. In contrast, FMRFa increases the amplitude of the
      contraction and slightly elevates the tone of the PRM but requires a higher
      threshold (10 microM). Assay by high-performance liquid chromatography of 5HT and
      DA in the PRM has shown that the 5HT level decreases during locomotion but
      increases during feeding, whereas the DA level increases during locomotion but
      slightly decreases during feeding. Thus, different segments of the PRM are
      innervated by neurons from different loci within the central nervous system. The
      segments of the PRM distal to the pharynx are innervated from loci of the
      subesophageal ganglion complex suggesting that they mediate withdrawal. The
      proximal segment of the PRM is innervated from cerebral and buccal loci
      indicating that these neurons mediate the feeding rhythm produced by buccal and
      cerebral feeding central pattern generators to induce rhythmic phasic
      contractions in the PRM during feeding.

PMID- 15959811
TI  - Symptomatic control of hypoglycaemia with prednisone in refractory metastatic
      pancreatic insulinoma.
AB  - A 55-year-old female presented with recurring episodes of loss or decline in the
      quality of consciousness due to hypoglycaemia caused by insulin overproduction in
      hormonally active metastatic pancreatic insulinoma. All standard anticancer
      treatment modalities including chemotherapy, radiation, interferon alpha 2b, and
      lanreotide failed to achieve symptomatic control. The patient became dependent on
      continuous intravenous glucose supply. Based on anecdotal reports in literature,
      prednisone therapy was started in order to increase insulin resistance, reduce
      glucose utilization, increase hepatic glucose production, and impair insulin
      secretion. After 10 days of therapy, the patient was released from continuous
      intravenous glucose infusion. After several weeks, administration of prednisone
      was lowered to a daily maintenance dose of 2.5 mg with excellent symptomatic
      effects. In conclusion, prednisone therapy may be considered as a valid option to
      achieve symptomatic control in hormonally active therapeutically resistant
      insulinomas.

PMID- 15959812
TI  - The influence of arbuscular mycorrhizae and light on Wisconsin (USA) sand savanna
      understories 2. Plant competition.
AB  - Wisconsin (USA) oak savannas are endangered plant communities that have
      remarkably high plant species diversity. To investigate factors underlying this
      richness, we experimentally investigated the potentially interacting effects of
      light gradients and arbuscular mycorrhizal fungi (AMF) on plant competition in
      the greenhouse, using a fully randomized block design. We used four plant
      species, soil, and AMF from a remnant sand savanna, under two light and five AMF
      treatments. Plants were grown four per pot under two competition treatments
      (either one or four species per pot) for 20 weeks. Using ANOVA, we found that all
      species showed significant treatment effects on total and shoot biomass,
      primarily due to differences in competition and light, less to AMF. However,
      effects were the opposite of predictions. Putatively mycorrhizal plants showed
      neutral to negative responses to AMF, and a nonmycorrhizal species outcompeted
      AMF species in infected pots. We concluded that our experimental setup of small
      pots, sandy soil, and long growing period had induced parasitism by the AMF on
      susceptible hosts. This unexpected result is consistent with field data from the
      sand savanna, and may help explain how nonmycorrhizal plants can compete
      successfully with AMF species in established, species-rich communities.

PMID- 15959813
TI  - Tetanus immunization among geriatric hospitalized patients.

PMID- 15959814
TI  - Epidemiological study of hepatitis B virus infection in Manitoba, Canada, 1992
      2003.
AB  - In comparison with other Canadian provinces and most Western countries, the
      province of Manitoba maintains a different vaccination policy for hepatitis B.
      This policy provides selective antenatal screening for hepatitis B in women and
      an inoculation program for hepatitis B vaccination for fourth-grade pupils. There
      has been increasing concern for this policy with regard to its influence on
      secular trends of acute hepatitis B incidence in Manitoba. This created a need to
      summarise the epidemiological characteristics of hepatitis B virus (HBV)
      infection in Manitoba and to allocate finances and human resources for future
      prevention programs. The Cadham Provincial Laboratory in Winnipeg, a Canadian
      Public Health Laboratory, is responsible for testing all specimens for diagnosis
      of various common infectious diseases in Manitoba. During the period from 1
      January 1992 to 31 December 2003, a total of 285,946 clinical specimens were
      submitted to this laboratory, which confirmed 310 cases of acute HBV and 7,556
      cases of chronic HBV infection. A total of 18,168 individuals were identified as
      having vaccine-induced immune status. The incidence rate of acute HBV infection
      has significantly decreased from 6.52/100,000 person-years in 1996 to
      0.86/100,000 person-years in 2003. Annual prevalence rates of chronic HBV
      infection in Manitoba increased slightly from 42.96 cases/100,000 population in
      1992 to 71.47 cases/100,000 population in 2003. Incidence rates were generally
      higher in men than in women at all age groups, with values of 2.65 and 1.65 per
      100,000 population, respectively (chi-square=15.768, p value <0.001). The highest
      incidence rate for both males and females was observed in the age group 30-34
      years. The North Eastman and Winnipeg Regional Health Authorities showed
      significantly higher incidence rates of acute hepatitis B compared with the other
      nine Regional Health Authorities. Selective hepatitis B vaccination programs for
      children in Manitoba had achieved the greatest success in the prevention of
      vertical and horizontal transmission. There is an urgent need to develop cost
      effective harm-reduction strategies for hepatitis B prevention among adults (aged
      30-34) and groups at risk in Manitoba.

PMID- 15959815
TI  - Human brucellosis in a nonendemic country: a report from Germany, 2002 and 2003.
AB  - Human brucellosis has become a rare disease in Germany since the eradication of
      bovine and ovine/caprine brucellosis in this country. Therefore, most physicians
      are unfamiliar with the illnesses clinical presentation, diagnostic tools, and
      therapeutic strategies. This retrospective study was carried out to evaluate the
      epidemiological, clinical, and laboratory features of human brucellosis in
      Germany in the years 2002 and 2003. Thirty-one bacterial isolates from 30
      patients sent to the German national reference laboratory were characterized
      using the genus-specific bcsp31 real-time PCR, the species-specific AMOS-PCR, and
      standard microbiological methods for the detection and identification of Brucella
      spp. The medical records of all patients with bacteriologically confirmed
      brucellosis were evaluated. All 31 isolates proved to be Brucella (30 Brucella
      melitensis and 1 Brucella suis). Most of the brucellosis patients were infected
      in endemic countries while visiting friends and relatives during their summer
      holidays. One case of laboratory-acquired infection was identified. Brucellosis
      was transmitted mainly by the consumption of contaminated unpasteurized milk or
      cheese from goats and sheep. The patients presented primarily with flu-like
      symptoms, i.e. fever, chills, sweating, headaches, arthralgia, and myalgia. In
      most cases, however, symptoms and signs of focal complications, e.g. spondylitis,
      endocarditis, and meningoencephalitis, predominated. The rate of complications
      was much higher than that in endemic countries, presumably as a result of
      diagnostic delay due to a low index of suspicion. In summary, physicians in
      nonendemic countries such as Germany must be aware of brucellosis being a
      possible cause of fever of unknown origin in immigrants and tourists travelling
      from endemic countries.

PMID- 15959816
TI  - An anatomically based patient-specific finite element model of patella
      articulation: towards a diagnostic tool.
AB  - A 3D anatomically based patient-specific finite element (FE) model of patello
      femoral (PF) articulation is presented to analyse the main features of patella
      biomechanics, namely, patella tracking (kinematics), quadriceps extensor forces,
      surface contact and internal patella stresses. The generic geometries are a
      subset from the model database of the International Union of Physiological
      Sciences (IUPS) (http://www.physiome.org.nz) Physiome Project with soft tissue
      derived from the widely used visible human dataset, and the bones digitised from
      an anatomically accurate physical model with muscle attachment information. The
      models are customised to patient magnetic resonance images using a variant of
      free-form deformation, called 'host-mesh' fitting. The continuum was solved using
      the governing equation of finite elasticity, with the multibody problem coupled
      through contact mechanics. Additional constraints such as tissue
      incompressibility are also imposed. Passive material properties are taken from
      the literature and implemented for deformable tissue with a non-linear micro
      structurally based constitutive law. Bone and cartilage are implemented using a
      'St-Venant Kirchoff' model suitable for rigid body rotations. The surface fibre
      directions have been estimated from anatomy images of cadaver muscle dissections
      and active muscle contraction was based on a steady-state calcium-tension
      relation. The 3D continuum model of muscle, tendon and bone is compared with
      experimental results from the literature, and surgical simulations performed to
      illustrate its clinical assessment capabilities (a Maquet procedure for reducing
      patella stresses and a vastus lateralis release for a bipartite patella).
      Finally, the model limitations, issues and future improvements are discussed.

PMID- 15959817
TI  - Functional groups based on leaf physiology: are they spatially and temporally
      robust?
AB  - The functional grouping concept, which suggests that complexity in ecosystem
      function can be simplified by grouping species with similar responses, was tested
      in the Florida scrub habitat. Functional groups were identified based on how
      species regulate exchange of carbon and water with the atmosphere as indicated by
      both instantaneous gas exchange measurements and integrated measures of function
      (%N, delta13C, delta15N, C:N ratio) in fire-maintained Florida scrub, which was
      considered the natural state for scrub habitat. Using cluster analysis, five
      distinct physiologically based functional groups were identified in the fire
      maintained scrub and were determined to be distinct clusters and not just
      arbitrary divisions in a continuous distribution by the non-parametric
      multivariate analysis of similarities (ANOSIM; R=0.649, P=0.005). These
      functional groups were tested for robustness spatially, temporally, and with
      management regime using ANOSIM. The physiological functional groups remained
      distinct clusters in this broader array of sites (R=0.794, P=0.001) and were not
      altered by plot differences, primarily, water table depth (R=-0.115, P=0.893) or
      by the three different management regimes: prescribed burn, mechanically treated
      and burned, and fire-suppressed (R=0.018, P=0.349). The physiological groupings
      also remained robust between the two climatically different years, with 1999
      being a much wetter year than 2000 (R=-0.027, P=0.725). Easy-to-measure
      morphological characteristics, if they indicate the same functional groups, would
      be more practical for scaling and modeling ecosystem processes than detailed gas
      exchange measurements; therefore, we tested a variety of morphological
      characteristics as functional indicators. A combination of non-parametric
      multivariate techniques were used to compare the ability of life form, leaf
      thickness (LT), and specific leaf area (SLA) classifications to identify the
      physiologically based functional groups. Life form classifications (ANOSIM;
      R=0.629, P=0.001) were able to depict the physiological groupings more adequately
      than either SLA (ANOSIM; R=0.426, P=0.001) or LT (ANOSIM; R=0.344, P=0.001). The
      ability of life forms to depict the physiological groupings was improved by
      separating the parasitic Ximenia americana from the shrub category (ANOSIM;
      R=0.794, P=0.001). Therefore, a life form classification including parasites was
      determined to be a good indicator of the physiological processes of scrub species
      and would be a useful method of grouping species for scaling physiological
      processes to the ecosystem level.

PMID- 15959818
TI  - Induced resistance in the indeterminate growth of aspen (Populus tremuloides).
AB  - Studies of induction in trees have examined rapid induced resistance (RIR) or
      delayed induced resistance (DIR), but have not examined induction that occurs in
      leaves produced by indeterminately growing trees subsequent to, but in the same
      season as, damage. We refer to induction that occurs during this time period as
      intermediate-delayed induced resistance (IDIR). We assessed the influences of
      genetic and environmental factors, and their interactions, on temporal and
      spatial variation in induction and on tradeoffs between induced and constitutive
      levels of resistance in indeterminately growing saplings of aspen (Populus
      tremuloides). We utilized a common garden of 12 aspen genotypes experiencing two
      levels of defoliation and two levels of soil nutrients. We assessed
      concentrations of phenolic glycosides and condensed tannins in damaged leaf
      remnants collected 1 week after defoliation to examine rapid and local induction,
      and in undamaged leaves produced 8 weeks after defoliation to assess intermediate
      delayed and systemic induction. In general, tannins showed RIR, while phenolic
      glycosides expressed IDIR. For both classes of allelochemicals, we found high
      estimates of broad-sense heritability and genetic variation in both induced and
      constitutive levels. Genetic variation may be maintained by both direct costs of
      allelochemicals and by costs of inducibility (phenotypic plasticity). Such costs
      may drive the tradeoff exhibited between induced and constitutive levels of
      phenolic glycosides. IDIR may be important in reducing total-season tissue loss
      by providing augmented resistance against late summer herbivores in trees that
      have experienced damage earlier in the season. Herbivore-resistant compensatory
      growth is especially beneficial to young trees growing in competitive
      environments.

PMID- 15959819
TI  - Influences of chronic and current season grazing by collared pikas on above
      ground biomass and species richness in subarctic alpine meadows.
AB  - We studied an alpine herbivory gradient established by collared pikas, a small
      central place foraging lagomorph, to examine the effects of multiple grazing
      levels on above-ground live biomass (AGB) and species richness (SR) in alpine
      tundra. The effects of within-season (four sampling periods), multi-season
      (across three summers) and longer-term dynamics (inferred from spatial location
      of vegetation with respect to pika haypiles) were examined. Along the grazing
      gradient, we found support for and against hypotheses that propose biphasic,
      increasing, or decreasing responses to herbivory, both in terms of AGB and SR.
      Our results suggest that plant-herbivore predictability is still weak. To further
      examine the impact of herbivory, we experimentally removed pikas using mesh
      exclosures placed at increasing distance from the edge of talus occupied by
      pikas. AGB after the second consecutive year of herbivore exclusion increased by
      125% compared to control plots in highly grazed areas adjacent to talus (<1 m).
      In more lightly grazed sites at distances 1-6 m from talus, AGB increased by more
      than 40% after pikas were removed. No differences were observed in the ungrazed
      sites >6 m from talus. AGB was highest in meadow patches previously grazed by
      pikas compared to those with little grazing history, but this response was only
      observed after two seasons following release from herbivory. Grazed sites at
      distances of 1-6 m had the highest SR. These results indicate that multi-year
      measurements of growth are particularly relevant in ecosystems dominated by long
      lived perennials in regions where productivity is low. Infrequent herbivore
      vacancies may provide local short-term release from pika grazing, thereby
      contributing to the persistence of productive, highly palatable vegetation.

PMID- 15959820
TI  - Two-phase seed dispersal: linking the effects of frugivorous birds and seed
      caching rodents.
AB  - Frugivorous birds disperse the seeds of many fruit-bearing plants, but the fate
      of seeds after defecation or regurgitation is often unknown. Some rodents gather
      and scatter hoard seeds, and some of these may be overlooked, germinate, and
      establish plants. We show that these two disparate modes of seed dispersal are
      linked in some plants. Rodents removed large (>25 mg) seeds from simulated bird
      feces (pseudofeces) at rates of 8-50%/day and scatter hoarded them in soil. Ants
      (Formica sibylla) also harvested some seeds and carried them to their nests.
      Rodents carried seeds 2.5+/-3.2 m to cache sites (maximum 12 m) and buried seeds
      at 8+/-7 mm depth. Enclosure studies suggest that yellow pine chipmunks (Tamias
      amoenus) and deer mice (Peromyscus maniculatus) made the caches. In spring, some
      seeds germinated from rodent caches and established seedlings, but no seedlings
      established directly from pseudofeces. This form of two-phase seed dispersal is
      important because each phase offers different benefits to plants. Frugivory by
      birds permits relatively long-range dispersal and potential colonization of new
      sites, whereas rodent caching moves seeds from exposed, low-quality sites (bird
      feces on the ground surface) to a soil environment that may help maintain seed
      viability and promote successful seedling establishment.

PMID- 15959821
TI  - Cell-mediated immunosenescence in birds.
AB  - The phytohaemagglutinin (PHA) skin test response, used to assess cell-mediated
      immunity, is known to vary with many social and energetic factors, but the
      effects of age have received little attention. We found that the PHA response of
      immature birds was lower than those of the youngest breeding adults and were
      decreased in adults. Whenever possible, age should be included as a covariate
      when the PHA skin test is used to assess immunocompetence in ecological
      immunology. The rate of decline in PHA response differed between species and was
      inversely correlated with survival. The decrease in the PHA response averaged 57%
      over an average 80% of the maximum life span, but the absolute rate varied with
      species lifespan such that the short-lived species showed a greater loss per year
      than the long-lived species. This link between declining immune function and
      survival may reflect differences in resource partitioning between species, and
      suggests that selection may act on investment in immune function to influence
      maximum life span.

PMID- 15959822
TI  - Resistance to herbicide and susceptibility to herbivores: environmental variation
      in the magnitude of an ecological trade-off.
AB  - Trade-offs can maintain genetic diversity and constrain adaptation; however,
      their magnitude may depend on ecological factors. I considered whether resistance
      to the herbicide triazine in Amaranthus hybridus (Amaranthaceae) imposed the
      trade-off of increasing susceptibility to herbivorous insects. I grew triazine
      resistant and triazine-susceptible plants under contrasting levels of light and
      fertilization, and quantified susceptibility to herbivores using the specialist
      Disonycha glabrata (Coleoptera: Chrysomelidae) and the generalist Trichoplusia ni
      (Lepidoptera: Noctuidae). Resistance to triazine increased susceptibility to both
      species of herbivorous insects, as manifested by greater feeding preference,
      growth, and survival of herbivores. However, these effects were more pronounced
      with T. ni and for plants grown under high light. My results demonstrate the
      presence of a trade-off between resistance to triazine and susceptibility to
      herbivorous insects that may in turn impose an ecologically based fitness cost,
      and illustrate the potential for this cost to vary across environments.

PMID- 15959823
TI  - Environmental sensitivity of gas exchange in different-sized trees.
AB  - The carbon isotope signature (delta13C) of foliar cellulose from sunlit tops of
      trees typically becomes enriched as trees of the same species in similar
      environments grow taller, indicative of size-related changes in leaf gas
      exchange. However, direct measurements of gas exchange in common environmental
      conditions do not always reveal size-related differences, even when there is a
      distinct size-related trend in delta13C of the very foliage used for the gas
      exchange measurements. Since delta13C of foliage predominately reflects gas
      exchange during spring when carbon is incorporated into leaf cellulose, this
      implies that gas exchange differences in different-sized trees are most likely to
      occur in favorable environmental conditions during spring. If gas exchange
      differs with tree size during wet but not dry conditions, then this further
      implies that environmental sensitivity of leaf gas exchange varies as a function
      of tree size. These implications are consistent with theoretical relationships
      among height, hydraulic conductance and gas exchange. We investigated the
      environmental sensitivity of gas exchange in different-sized Douglas-fir
      (Pseudotsuga menziesii) via a detailed process model that specifically
      incorporates size-related hydraulic conductance [soil-plant-atmosphere (SPA)],
      and empirical measurements from both wet and dry periods. SPA predicted, and the
      empirical measurements verified, that differences in gas exchange associated with
      tree size are greatest in wet and mild environmental conditions and minimal
      during drought. The results support the hypothesis that annual net carbon
      assimilation and transpiration of trees are limited by hydraulic capacity as tree
      size increases, even though at particular points in time there may be no
      difference in gas exchange between different-sized trees. Maximum net ecosystem
      exchange occurs in spring in Pacific Northwest forests; therefore, the presence
      of hydraulic limitations during this period may play a large role in carbon
      uptake differences with stand-age. The results also imply that the impacts of
      climate change on the growth and physiology of forest trees will vary depending
      on the age and size of the forest.

PMID- 15959824
TI  - Using stable isotope analysis with telemetry or mark-recapture data to identify
      fish movement and foraging.
AB  - Information about animal movements has often been inferred from stable isotope
      analysis (SIA), but is dependent on animals assimilating site-specific isotopic
      signatures via diet. This potential weakness in ecological interpretation can be
      overcome by using other investigative tools that provide precise information
      about individual movement patterns. In this paper, we demonstrate the value of
      combining SIA with telemetry or mark-recapture data from trapping, electrofishing
      and remote detection of individuals to study the movement and feeding ecology of
      fishes in different habitats. In a fjord lake system in Newfoundland, Canada,
      juvenile Atlantic salmon delayed downstream migration (smolts) or actively moved
      into a large lake (parr) where they foraged for periods reflecting different life
      history strategies. In the Miramichi River (New Brunswick, Canada), SIA provided
      evidence of distinct foraging habitats (tributary versus large river). By
      tracking fish implanted with passive integrated transponder (PIT) tags, we
      distinguished between movements related to foraging versus seeking cool water
      refugia during high temperature events. Finally, site fidelity and limited
      mobility of slimy sculpin, a small benthic fish, was established where delta13C
      in muscle tissue showed a progressive enrichment downstream and where a median
      displacement of <10 m was estimated for sculpin tagged with PIT tags.
      Technological improvements have permitted non-destructive tissue sampling of wild
      fishes for SIA, and the tagging and remote detection of animals smaller than was
      previously possible. These advancements and the combination of investigative
      tools promise new insights into animal ecology.

PMID- 15959825
TI  - Carboplatin plus paclitaxel in the treatment of advanced or recurrent endometrial
      carcinoma.
AB  - PURPOSE: To evaluate the efficacy and safety of the combination of carboplatin
      plus paclitaxel in patients with advanced, metastatic and recurrent endometrial
      cancer. METHODS: Medical records were retrospectively reviewed to identify
      endometrial cancer patients treated in the Gynecologic Cancer Program of the
      Cleveland Clinic with carboplatin/paclitaxel who had both a histologic diagnosis
      of endometrial adenocarcinoma and either measurable (CT scan, physical
      examination) or evaluable (CA-125 criteria) disease. RESULTS: From 1994 to 2003,
      22 individuals (median age 65 years) meeting the above noted criteria received a
      total of 23 courses of carboplatin (AUC 4-6)/paclitaxel (135-175 mg/m2)
      administered on a 21-day schedule (median six cycles/patient). The overall
      response rate was 87% (20/23). The most common toxicity was hematologic. Five
      patients required dose reductions due to excessive toxicity (three hematologic,
      one gastrointestinal, one fatigue). There were no treatment related deaths. With
      a median follow-up of 42 months, 13 patients have died of progressive cancer,
      while four currently have no evidence of disease at the time of last follow-up.
      CONCLUSIONS: The combination of carboplatin plus paclitaxel demonstrates
      substantial biological activity in endometrial adenocarcinoma. The safety and
      efficacy of this regimen makes it an attractive option for first-line
      chemotherapy in patients with advanced or recurrent endometrial carcinoma.

PMID- 15959826
TI  - [German Acupuncture Trials (gerac) address problems of methodology associated
      with acupuncture studies].
AB  - OBJECTIVE: Conflicting or ambivalent findings on the effectiveness of body
      acupuncture in pain treatment are often attributed to flaws in study methodology.
      The paper describes the methodology used for the German Acupuncture Trials
      (gerac), which demonstrates that it is possible to design acupuncture studies in
      accordance with the standards of good clinical practice. METHOD: Approximately
      1000 chronic pain sufferers per indication (migraine, tension-type headache, low
      back pain (cLBP), or gonarthrosis) are randomly allocated to one of three
      treatment groups (verum acupuncture, sham acupuncture, or established
      conservative therapy). Patients are blind to the type of acupuncture. All
      patients receive ten sessions of treatment (two per week) with an option of
      adding five more treatments in cases of slight but insufficient improvement
      (number of headache days or von Korff pain score). Participating physicians are
      in private practice, representing a variety of specialties. All have completed at
      least a 140-hour training course in acupuncture. Mandatory and optional verum and
      sham points are predefined. The point selection is individualized according to
      the criteria of traditional Chinese medicine (TCM). Primary outcome measures are
      number of headache days per month, von Korff Graded Chronic Pain Scale or
      Hannover Functional Ability Questionnaire (cLBP), or WOMAC scores (gonarthrosis).
      Data are assessed by trained telephone interviewers not involved in treatment and
      blind to types of acupuncture. PRESENT STATUS: Over 500 participating physicians
      in ten urban areas of Germany. Patient recruitment for cLBP and gonarthrosis was
      completed in November 2003 and March 2004 respectively. Recruitment for chronic
      headaches will be completed in autumn 2004. CONCLUSIONS: The gerac trials prove
      that it is possible to design and carry out acupuncture studies in accordance to
      stringent standards of methodology and clinical practice. The results will form a
      basis for the assessment of acupuncture effectiveness in Germany and abroad.

PMID- 15959827
TI  - Results of spinal meningioma surgery in patients with severe preoperative
      neurological deficits.
AB  - Spinal meningiomas are usually benign, slow-growing tumours and are commonly
      associated with good patient outcome following surgery. However, the existence of
      a severe preoperative neurological deficit has been considered to be a possible
      predictor of poor functional outcome after surgery. We retrospectively reviewed
      data from 33 patients with 35 spinal meningiomas treated in our institution over
      the past 17 years and exhibiting severe preoperative deficits before surgery.
      Among them, 20 suffered from paraparesis and 13 were paraplegic. The mean follow
      up duration was 70.7 months (range 12-183 months). By the 1-year follow-up, all
      patients had improved in comparison with their preoperative neurological status,
      and 60% of them had totally recovered. It can be concluded from this study, that,
      in the vast majority of cases, patients harbouring spinal meningioma with severe
      preoperative deficits can expect a good outcome.

PMID- 15959829
TI  - Efficacy of different whitening modalities on bovine enamel and dentin.
AB  - Previous studies have shown that bleaching treatment may be efficient in both
      enamel and dentin, but it is still unknown how much the subsurface dentin
      contributes to the color change of teeth. This in vitro study evaluated the
      whitening effect of different external bleaching agents on enamel-dentin slabs
      and subsurface dentin. Ninety bovine teeth were distributed among six groups (A,
      Opalescence 10%; B, Opalescence PF 15%; C, Opalescence Quick; D, Opalescence
      Extra Boost; E, Rapid White; F, Whitestrips). Two enamel-dentin specimens were
      prepared from the labial surface of each teeth. In one of the specimens enamel
      was removed, resulting in a dentin (CD) disc of 1 mm high. The labial and the
      pulpal sides of the second specimen were ground until the remaining enamel and
      dentin layers of the enamel-dentin sample (ED) were 1 mm each. Whitening
      treatment of the ED specimens was performed according to manufacturers'
      instructions. Pre- and posttreatment Lab values of ED samples were analyzed using
      CIE-Lab. Baseline Lab values of dentin were analyzed by evaluation of the CD
      specimen. Finally, enamel of the ED specimens was removed and color change of the
      exposed dentin (D) was recorded. For all treatment agents significant color
      changes (DeltaE) were observed for enamel-dentin samples and subsurface dentin
      specimens compared to controls. In groups A-D DeltaE was significantly higher in
      dentin than enamel-dentin. Furthermore, L and b values of bleached enamel-dentin
      and subsurface dentin samples differed significantly from baseline. Treatment
      with the tested external whitening bleaching agents resulted in color change of
      both enamel-dentin and subsurface dentin samples. The results indicate that color
      change of treated teeth might be highly influenced by color change of the
      subsurface dentin.

PMID- 15959832
TI  - Genetic variation and population structure of an isolate of Citrus exocortis
      viroid (CEVd) and of the progenies of two infectious sequence variants.
AB  - The population structure and diversity within a Citrus exocortis viroid (CEVd)
      isolate was estimated by single strand conformation polymorphism (SSCP) and
      sequence analysis. A predominant sequence variant (V1) representing 52.8% of the
      overall population was identified. V1 and other additional variants presented a
      composition of the P domain characteristic of severe strains of CEVd. The
      nucleotide diversity of this CEVd population was lower than expected according to
      a model of neutral evolution, suggesting a strong negative selection. Citron
      plants were inoculated with dimeric clones of nine sequence variants and two
      resulted infectious inducing the severe symptoms characteristic of the original
      isolate. De novo populations were generated from these infectious variants and
      like in the original CEVd isolate, both populations presented V1 as the
      predominant variant but they evolved to a higher nucleotide diversity.

PMID- 15959831
TI  - Prolonged exposure of rats to intravenous methamphetamine: behavioral and
      neurochemical characterization.
AB  - The translational value of preclinical models of methamphetamine abuse depends in
      large part on the degree to which the drug regimens used in animals produce
      methamphetamine exposure patterns similar to those experienced by human
      methamphetamine abusers. To approximate one common form of methamphetamine abuse,
      we studied the effects of a schedule of intravenous methamphetamine
      administration in rats which included 2 weeks of progressively more frequent drug
      injections (0.125 mg/kg/injection) followed by 40 maintenance days during which
      animals received 40 daily injections (at 15-min intervals), with the dose
      gradually increasing (0.125-0.25 mg/kg per injection) every 5-10 days. This
      treatment produced an emerging behavioral profile characterized by gradually more
      continuous periods of activation consisting of progressively more intense,
      focused stereotypy interrupted by episodic bursts of locomotion. We also assessed
      markers of dopamine neurotransmission (dopamine transporter, vesicular monoamine
      transporter, and dopamine D1 and D2 receptors) at 15 min and (including dopamine
      levels) at 6 and 30 days following cessation of methamphetamine treatment. All
      dopamine components measured in caudate-putamen were significantly reduced at 15
      min and 6 days after the final methamphetamine injection. Dopamine D1 and D2
      receptors fully recovered after 30 days of drug abstinence, whereas dopamine and
      the dopamine transporter exhibited significant but incomplete recovery by this
      time point. In contrast, only the vesicular monoamine transporter exhibited no
      evidence of recovery over the 30-day withdrawal period. These data are discussed
      in terms of damage to dopamine terminals and compensatory adjustments in
      mechanisms maintaining functional dopaminergic transmission.

PMID- 15959833
TI  - Rotavirus antigenemia in children with encephalopathy accompanied by rotavirus
      gastroenteritis.
AB  - Rotavirus antigen was detected in acute phase sera from 5 of 8 children with
      rotavirus-associated encephalopathy, confirming antigenemia. However, antigen was
      not detected in cerebrospinal fluid, failing to provide added evidence of
      invasion to the brain.

PMID- 15959834
TI  - Proposal for genetic characterisation of wild-type mumps strains: preliminary
      standardisation of the nomenclature.
AB  - Though mumps virus (MuV) is a monotypic virus, genetic variation between strains
      has been described. Viruses have been placed into genotypes designated A-L based
      on the nucleotide sequence of the small hydrophobic (SH) gene, which is the most
      variable gene in the mumps genome. Molecular characterisation of MuV is an
      important component of mumps surveillance because it can help identify the
      transmission pathways of the virus as well as distinguish between wild-type and
      vaccine strains. Here, we propose a standardized nomenclature and an analysis
      protocol for the genetic characterisation of mumps strains to facilitate
      expansion of molecular epidemiological studies. In addition to assigning standard
      reference strains for the recognized genotypes of MuV, a convention is proposed
      for naming for strains and criteria to designate a new genotype.

PMID- 15959835
TI  - Polymorphism of HIV-1 gag (p17) gene from female sex workers in Calcutta, India.
AB  - HIV-1 subtype C is the major subtype in India as evidenced from the analysis of
      specific regions within envelope and gag gene. The matrix protein (p17) of HIV-1
      which is involved in several functions like the viral RNA transport, nuclear
      localization, assembly of pre-integration complex into host nucleus has been used
      to study the strain diversity among female sexworkers in Calcutta. The gene
      encoding for the HIV-1 matrix protein, p17 was amplified by nested polymerase
      chain reaction (PCR) from blood samples of HIV-1 seropositive female sex workers
      (FSW) in Calcutta, India. Genes of twenty-two samples were sequenced and the
      phylogenetic analysis with different global strains showed that the majority
      (seventeen) was clustered with Indian type C. A few samples were found to be
      close to other C subtypes isolated from South Africa, China and Myanmar. The
      comparison of Calcutta samples with the samples from other regions of India along
      with other non-asian subtype C sequences clearly revealed a different cluster of
      Indian sequences. The two samples, cal 242 and cal 709 was found to be the most
      divergent type and showed close relatedness with African C subtypes.

PMID- 15959836
TI  - Characterization of the host cell entry of filamentous influenza virus.
AB  - Most laboratory-adapted strains of influenza virus exist as spheres of
      approximately 100 nm in diameter, which are well established to enter cells by
      endocytosis in a pH-dependent manner. However, influenza virus isolated from the
      lungs of infected individuals is believed to exist as predominantly filamentous
      particles, up to several micrometers in length. Here, we have attempted an
      initial characterization of the entry of purified influenza virus filaments into
      host cells--in comparison to more commonly studied spherical forms of the virus.
      We demonstrate that the internalization of filamentous influenza virus particles
      is delayed, relative to spherical particles, and that this delay is a result of
      morphological rather than strain differences. The filamentous influenza particles
      appear to retain their dependence on low-pH for entry, as demonstrated by a
      vacuolar-ATPase inhibitor, and viral trafficking to late endosomes, as
      demonstrated by the requirement for protein kinase C function. However, our data
      suggest that the endocytic uptake of the filamentous virus particles may be
      dynamin-independent, unlike spherical virions. Overall, these data provide a view
      of the entry of influenza virus in its filamentous morphology, demonstrating
      potential differences between the endocytosis of spherical virions in vitro and
      filamentous virions in vivo.

PMID- 15959837
TI  - Inhibitory effect of hexamethylene bisacetamide on replication of human
      cytomegalovirus.
AB  - The effect of hexamethylane bisacetamide (HMBA), a hybrid polar compound, on gene
      expression and replication of human cytomegalovirus (HCMV) was studied. When HCMV
      infected human thyroid papillary carcinoma (TPC-1) and human embryonic lung (HEL)
      fibroblast cells were maintained with medium containing 2.5 and 5 mM HMBA for 10
      days, there was a greater than 2- to 3-log reduction in virus yield compared to
      that in untreated cells. Infection of TPC-1 cells with HCMV resulted in an
      establishment of persistent infection and the cells continuously produced virus
      with titer of over 10(5) PFU/ml, whereas HMBA prevented the infected cells from
      entering into the persistent infection. Moreover, treatment of the persistently
      infected cultures with HMBA reduced production of infectious HCMV more
      efficiently than did ganciclovir, and eventually ceased HCMV production. Western
      blotting analysis revealed that HMBA blocks accumulation of the immediate early 2
      (IE2) protein in TPC-1 cells and delays synthesis of this protein in HEL cells,
      but has little effect on the level of the IE1 protein during the early times
      after infection. Synthesis of the viral early and late proteins in both cells was
      also substantially blocked by HMBA. The results indicate that the inhibition or
      the delay of the critical IE2 protein synthesis in the presence of HMBA would
      actually be a process that fails to proceed beyond the IE stages in HCMV
      replication cycle.

PMID- 15959838
TI  - Traumatic brain injury: cause or risk of Alzheimer's disease? A review of
      experimental studies.
AB  - Traumatic Brain Injury is the leading cause of death and disability among young
      individuals in our society. Moreover, according to some epidemiological studies,
      head trauma is one of the most potent environmental risk factors for subsequent
      development of Alzheimer's disease. Interestingly, pathological features that are
      present also in Alzheimer's disease (in particular deposition of beta-amyloid
      protein) were observed in traumatised brains already a few hours after the
      initial insult. The primary objective of this review is to present methodology
      and results of numerous recent human and animal studies dealing with this issue.
      Special emphasis was placed on head trauma experiments in transgenic mouse models
      of Alzheimer's disease. We further evaluate the connection between traumatic
      brain insults and subsequent development of dementia and try to differentiate
      between primary and secondary pathological mechanisms.

PMID- 15959839
TI  - Transcription factor AP-2 and monoaminergic functions in the central nervous
      system.
AB  - In the central nervous system, transcription factor AP-2 family is one of the
      critical regulatory factors for neural gene expression and neuronal development.
      Several genes in the monoaminergic systems display AP-2 binding sites in
      regulatory regions. In addition, brainstem levels of transcription factor AP
      2alpha and AP-2beta are positively correlated to monoamine measures in rat
      forebrain, suggesting a regulatory role of AP-2 also in the adult brain. Great
      changes in psychiatric phenotypes due to genetic factors are seldom the result of
      a single gene polymorphism. Recently, identification of combinations of candidate
      genes that are all linked to one disease or psychiatric phenotype has been
      discussed. The expression of these candidate genes might be regulated by the same
      transcription factors, e.g. AP-2. Recent data on transcription factor AP-2 family
      in relation to monoaminergic functions are described in this paper. Transcription
      factor AP-2beta genotype has been studied in relation to personality, platelet
      monoamine oxidase (MAO) activity, CSF-levels of monoamine metabolites, binge
      eating disorder, premenstrual dysphoric disorder, and schizophrenia. Furthermore,
      the involvement of AP-2 in the molecular mechanism of antidepressant drugs is
      discussed. Altogether, this paper discusses data supporting a notion that the
      transcription factor AP-2 family is involved in the regulation of the
      monoaminergic systems both pre- and postnatally, and, therefore, might be
      involved in the pathophysiology of neuropsychiatric disorders.

PMID- 15959840
TI  - Isolation rearing or methamphetamine traumatisation induce a "dysconnection" of
      prefrontal efferents in gerbils: implications for schizophrenia.
AB  - A miswiring of prefrontal efferents is generally discussed by the name of
      "dysconnection" as the anatomical substrate of schizophrenia. Since direct
      histological confirmation of this hypothesis can hardly be obtained in humans, we
      used an animal model of schizophrenia to trace prefrontal efferents to distal
      cortical fields. Mongolian gerbils were intoxicated with a single high dose of
      methamphetamine on postnatal day 14 and reared in isolation after weaning (day
      30). Controls received a saline injection and/or were reared under enriched
      conditions. Upon reaching adulthood (day 90), biocytin was injected into the
      medial prefrontal cortex into either deep or superficial laminae. The density of
      passing fibres and terminal fields in the frontal, parietal and insular cortices
      was assessed by digital image analysis. Isolation rearing or methamphetamine
      treatment alone reduced the projections from lamina V/VI to the frontal and from
      lamina III to the insular cortex, and from both laminae to the parietal cortex.
      In contrast, isolation rearing of methamphetamine-intoxicated gerbils
      significantly increased the projections from the deep laminae to the frontal and
      parietal cortices, compared to isolation-reared controls, with no difference in
      the efferents from superficial laminae. These results are the first to
      demonstrate a miswiring of prefrontal efferents in response to adverse systemic
      influences. They might give a hint at the anatomical basis of "dysconnection" in
      schizophrenia.

PMID- 15959841
TI  - Efficacy and safety of a new Botulinum Toxin Type A free of complexing proteins
      in the treatment of blepharospasm.
AB  - NT 201 is a new development of Botulinum Toxin Type A free of complexing
      proteins. In this double-blind Phase III trial, we compared the efficacy and
      safety of NT 201 and BOTOX in patients suffering from blepharospasm. Of 304
      enrolled patients, 300 patients received study medication (intent-to-treat
      population), and 256 patients completed the study as planned (per-protocol
      population). At baseline, patients received a single injection of NT 201 or BOTOX
      (<or=35 units per eye). No significant differences were found between NT 201 and
      BOTOX for all efficacy and safety variables three weeks after injection. Both the
      NT 201 and the BOTOX group showed a decrease in the Jankovic Rating Scale (JRS)
      sum score signifying an improvement in the symptoms of blepharospasm during this
      time period. These data show that NT 201* is an effective and safe treatment for
      patients suffering from blepharospasm.

PMID- 15959842
TI  - mPer1 and mPer2 mutant mice show regular spatial and contextual learning in
      standardized tests for hippocampus-dependent learning.
AB  - Learning and memory, like most physiological processes, seem to be under the
      control of circadian rhythm. The recently cloned mPer1 and mPer2 genes play an
      important role in the regulation of the circadian rhythm. In this study, we
      tested mPer1 and mPer2 mutant mice in two different learning and memory
      paradigms, a water-maze place navigation task and contextual fear conditioning.
      In both learning tests, the hippocampus is critically involved. None of these
      learning types were affected by the mutations, suggesting that mPer1 and mPer2 do
      not play a major role in the regulation of hippocampus-dependent learning and
      memory.

PMID- 15959843
TI  - Brain perfusion SPECT in patients with mild cognitive impairment and Alzheimer's
      disease: comparison of a semiquantitative and a visual evaluation.
AB  - Due to the increasing importance of early recognition and differential diagnosis
      of dementias, cerebral perfusion scans using "single photon emission computed
      tomography" (SPECT) are increasingly integrated into the examination routine. The
      goal of this study was to check the diagnostic validity of SPECT scans of MCI-
      and DAT-patients, two subgroups out of 369 persons with etiologically unclear
      cognitive dysfunction, which underwent an assessment program for probable
      dementia including cognitive testing, cranial computed tomography, ultrasound,
      routine laboratory testing including vascular risk factors. After exclusion of
      patients with no or other forms of dementia we analyzed SPECT data of patients
      with mild cognitive impairment (MCI; n = 85) and dementia of the Alzheimer type
      (DAT; n = 78) in comparison with a healthy control group (n = 34).Visual
      assessment as well as a manual "regions of interest" (ROI) regionalization of the
      cortex were performed, whereby a ROI/cerebellum ratio was calculated as a semi
      quantitative value. Association cortex areas were assessed regarding frontal,
      temporal, and parietal lobes of both hemispheres. When comparing the ratios of
      patients with DAT and controls, we found a statistically significant reduction of
      the cerebral perfusion in all measured cortex areas (p < 0.001). The comparison
      of patients with MCI with the selected control group also established a
      statistically significant difference in the cerebral perfusion for the evaluated
      cortex areas with the exception of the left hemispheric frontal and parietal
      cortex.A considerable number of the MCI patients showed an MMSE-score within the
      normal range, but with regard to the perfusion in the right hemispheric
      association cortex these patients also could be distinguished unambiguously from
      controls. Sensitivity levels found by visual assessment were at least as high as
      those found by the ROI method (pathological assessment: visual 49.4% vs. ROI
      47.1% for MCI; visual 75.6% vs. ROI 73.1% for DAT). High experienced visual
      assessment of cerebral perfusion scans using SPECT provides an useful additional
      tool in diagnosis of cognitive impairment. The used semiquantitative ROI-method
      is nearly equivalent and does not depend on the experience of the investigator.

PMID- 15959844
TI  - Implication of increased NRSF/REST binding activity in the mechanism of ethanol
      inhibition of neuronal differentiation.
AB  - The neuron-restrictive silencer factor (NRSF), or repressor element-1 silencing
      transcription factor (REST), is a transcription factor that mediates negative
      regulation of neuronal genes. NRSF represses multiple neuronal target genes in
      non-neuronal and neuronal precursor cells to regulate the proper timing of
      neuronal gene expression during neurogenesis. In the present study, we
      investigated the effects of ethanol and MEK inhibitor U0126 on the DNA binding
      activity of NRSF in neural stem cells prepared from rat embryos. Both ethanol and
      U0126 enhanced NRSF binding activity measured by the method based on the
      principal of electrophoretic mobility shift assay (EMSA) and decreased neuronal
      differentiation in a concentration dependent manner. Western blot analysis
      revealed that ethanol suppressed phosphorylation of extracellular signal
      regulated kinase (ERK) without affecting expression of total ERK. These results
      suggest that ethanol-induced potentiation of NRSF binding activity underlies the
      mechanism of ethanol inhibition of neuronal differentiation and decreased
      neurogenesis.

PMID- 15959845
TI  - Polymorphism in neuropeptide Y influences CSF cholesterol levels but is no major
      risk factor of Alzheimer's disease.
AB  - Neuropeptide Y (NPY) is a neurotransmitter expressed in the central nervous
      system and involved in learning and memory. The NPY L7P polymorphism has been
      associated with altered cholesterol levels in obese patients. Since altered
      cholesterol metabolism is also involved in Alzheimer's disease (AD), the effects
      of two NPY polymorphisms (L7P and IVS1-100 T/G) on CSF and plasma cholesterol and
      24S-hydroxycholesterol were investigated in AD patients and non-demented
      controls. Furtheremore, the effect of both NPY polymorphisms on the risk of AD
      was studied. The NPY IVS1-100 T/G polymorphism influenced CSF levels of
      cholesterol, whereas CSF and plasma levels of 24S-hydroxycholesterol and plasma
      cholesterol were not altered by genotype. NPY L7P polymorphism did not influence
      CSF or plasma cholesterol or 24S-hydroxycholesterol. Both NPY polymorphisms did
      not influence the risk of AD. Our data support the observation, that NPY
      polymorphisms might influence cholesterol metabolism, but might not act as major
      risk factor in AD.

PMID- 15959846
TI  - Overexpression of amyloid precursor protein induces susceptibility to oxidative
      stress in human neuroblastoma SH-SY5Y cells.
AB  - In Alzheimer's disease amyloid beta peptide (Abeta) produced from amyloid
      precursor protein (APP) is considered to induce cell death. To clarify the
      molecular mechanism underlying Abeta neurotoxicity, we established the cell line
      overexpressing wild or mutant (His684Arg) APP in human SH-SY5Y cells. This paper
      presents that overexpression of wild-APP in the cells (SH/w-APP) increased the
      levels of APP and Abeta(1-40) but not Abeta(1-42), and reduced Bcl-2 level and
      proteasome activity with increased susceptibility to oxidative stress. The
      intracellular levels of reactive oxygen species in SH/w-APP increased
      significantly by H(2)O(2) treatment. The level of Bcl-2 protein, but not mRNA,
      was markedly decreased in SH/w-APP cells, which was inversely correlated with APP
      expression among subcloned SH/w-APP cells. These results indicate that increased
      expression of wild type APP renders neuronal cells more vulnerable to oxidative
      stress leading to cell death.

PMID- 15959847
TI  - The maturation of the acetylcholine system in the dentate gyrus of gerbils
      (Meriones unguiculatus) is affected by epigenetic factors.
AB  - The current study investigated the influence of impoverished rearing (IR)
      conditions and a single early methamphetamine challenge (MA; 50 mg/kg i.p.) on
      day 14 on the postnatal maturation of acetylcholinesterase-positive (AChE+)
      fibres in the hippocampal dentate gyrus (DG) of gerbils (Meriones unguiculatus).
      The layer-specific densities of histochemically stained AChE+ fibres were
      quantified in two planes of the left and right DG in young adults (day 90).
      Compared to enriched reared (ER) animals, the AChE+ fibre densities turned out to
      be higher in both the septal and the temporal plane of both hemispheres in saline
      treated IR and MA treated ER gerbils. The temporal plane was slightly more
      affected than the septal plane. In IR animals, MA treatment selectively
      diminished the AChE+ fibre densities in the subgranular layer of both left and
      right temporal DG. In conclusion, the maturation of AChE+ fibres is vulnerable to
      both rearing conditions and early MA challenge. The results correlate with our
      previous studies on the dentate cell proliferation rates and the serotonergic
      innervation, two parameters which are similarly affected by the experimental
      design. Thus, disturbances of the ACh system may impair the hippocampal
      plasticity and hippocampus-related cognitive and emotional function.

PMID- 15959848
TI  - Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome.
AB  - Assessment of reactive oxygen species (ROS) is highly important in
      neurodegenerative disorders and neuroleptic treatment. However, conflicting
      results have been reported, which may arise from methodological difficulties.
      Obstructive sleep apnea (OSA) syndrome with episodic hypoxia-reoxygenation is
      proposed as a human model for the investigation of ROS measurements. Despite a
      broad analytical approach comprising lipid peroxidation and amino acid oxidation
      products, oxidative DNA damage, and activity of the antioxidant defense, only
      plasma malondialdehyde (MDA) and urinary o,o'-dityrosine seemed to be
      appropriate, robust biomarkers of oxidative stress, which are also simple enough
      for routine clinical use. MDA concentrations correlated with a duration of
      nocturnal desaturation below 85% (r = 0.77, p<0.0005), and o,o'-dityrosine levels
      decreased after therapy (p<0.05) as a function of baseline concentrations (r = 
      0.61, p<0.05). Gender effects in ROS generation also have to be considered. At
      present, we recommend the application of several oxidative stress measurements at
      different time points, preferably involving plasma MDA and urinary o,o'
      dityrosine.

PMID- 15959849
TI  - Motor learning of hands with auditory cue in patients with Parkinson's disease.
AB  - In the present research, changes in motor cortex function were observed in
      relation to repetitive, voluntary thumb movement (training) in patients with
      Parkinson's disease (PD) and normal control subjects. Changes in the direction of
      thumb movement due to motor evoked potential (MEP) by transcranial magnetic
      stimulation (TMS), after motor training with and without rhythmic sound, were
      measured using a strain gauge for 12 patients with PD and 9 normal control
      subjects. PD patients who experienced the freezing phenomena showed poor change
      in direction of TMS-induced movement after self-paced movement; however, marked
      change in direction of TMS-induced movement was observed after training with
      auditory cue. PD patients who had not experienced the freezing phenomena showed
      positive effects with the auditory cue, producing similar results as the normal
      control subjects. Two routes for voluntary movement are available in the nervous
      system. The decreased function of basal ganglia due to PD impaired the route from
      the basal ganglia to the supplementary motor cortex. These data suggest that the
      route from sensory input to cerebellum to premotor cortex could compensate for
      the decreased function of the route via the basal ganglia to the premotor cortex.
      Once change in the motor cortex occurred, such change persisted even after the
      interruption of training. These phenomena suggest that motor memory can be stored
      in the motor cortex.

PMID- 15959850
TI  - PP2B isolated from human brain preferentially dephosphorylates Ser-262 and Ser
      396 of the Alzheimer disease abnormally hyperphosphorylated tau.
AB  - PP2B is one of the major serine/threonine phosphatases in the brain. We
      quantitated the dephosphorylation of various sites of Alzheimer disease
      abnormally hyperphosphorylated tau by PP2B purified from six (three Alzheimer and
      three control) autopsied human brains. The purified PP2B was essentially
      homogenous holoenzyme as determined by SDS-PAGE, Western blot analyses and
      biochemical characterization. Purified PP2B from all six brains efficiently
      dephosphorylated (32)P-tau with specific activities ranging from 684-1286 pmol
      (32)Pi/mg/min. Estimated by dot-blot analyses, the purified PP2B (on average from
      six brains) dephosphorylated Alzheimer tau at pS199, pT217, pS262, pS396 and
      pS422 by 38%, 32%, 63%, 78%, and 32%, respectively. Dephosphorylation of tau at
      pT181, pS202, pT205, pT212, pS214, and pS404 by PP2B was undetectable. The
      preferential dephosphorylation of Ser262 and Ser396 by PP2B suggests a possible
      involvement of this phosphatase in Alzheimer neurofibrillary degeneration.

PMID- 15959851
TI  - [(11)C]d-threo-methylphenidate PET in patients with Parkinson's disease and
      essential tremor.
AB  - Twenty Parkinson's disease (PD) patients, 6 patients with essential tremor and 10
      healthy controls were studied with the dopamine transporter ligand [(11)C]d-threo
      methylphenidate ([(11)C]dMP) and positron emission tomography (PET) to assess
      dopamine terminal loss in relation to disease duration and motor disability.
      Dopamine transporter availability was expressed as [(11)C]dMP binding potential
      (BP(dMP)) in percentage of the mean of healthy controls. In PD patients (age at
      onset 57.7 +/- 8.9 yrs; disease duration 5.2 +/- 3.3 yrs; UPDRS motor score 24.2
      +/- 9.8; Hoehn & Yahr 2.1 +/- 0.8; mean +/- SD) BP(dMP) was reduced to 30%
      (range: 11-55%) in the putamen and 52% (range: 14-96%) in the caudate nucleus.
      BP(dMP) in the putamen closely correlated with the UPDRS motor score (r = -0.79,
      p < 0.001), and disease duration (r = -0.76, p < 0.001) but not with age at
      onset. The correlation with the UPDRS score depended on akinesia and rigidity,
      while the tremor scores were related neither to putamen nor caudate BP(dMP).
      Interestingly, when plotted over disease duration, PD patients with severe
      asymmetry of symptoms showed significantly lower BP(dMP) in the contralateral
      putamen (exponential fit: 34% at onset) than the other PD patients (41% at
      onset), indicating a different symptomatic threshold of these subgroups and an
      even closer correlation with the hypothetical "true" disease duration. The
      exponential fit across all patients indicated a mean symptomatic threshold of 37%
      contra- and 62% ipsilateral, corresponding with an observed mean BP(dMP) of 51%
      (average contra- and ipsilateral) in those patients with disease duration less
      than one year. No differences in BP(dMP) were observed between patients with
      essential tremor and healthy controls. [(11)C]dMP appears to be a useful and
      sensitive marker of dopaminergic dysfunction in PD and can be used to assess and
      monitor disease severity.

PMID- 15959852
TI  - Gait analysis in patients with advanced Parkinson disease: different or additive
      effects on gait induced by levodopa and chronic STN stimulation.
AB  - The aim of our study was to observe the effects on gait parameters induced by STN
      stimulation and levodopa medication in patients with advanced Parkinson's disease
      in order to determine different or additive effects. Therefore we examined 12
      patients with advanced Parkinson disease after bilateral implantation of DBS into
      the STN. We assessed the motor score of the UPDRS and quantitative gait analysis
      under 4 treatment conditions: with and without stimulation as well as with and
      without levodopa. The mean improvement of the UPDRS motor score was almost the
      same with levodopa and DBS. Combining both therapies we saw a further improvement
      of the motor score. Gait parameters of patients with PD treated either with
      levodopa or STN stimulation were greatly improved. A significant difference
      between levodopa and STN stimulation could only be shown for the parameters
      velocity and step length. These parameters improved more with levodopa than with
      stimulation. The combination of both therapeutic methods showed the best results
      on the UPDRS motor score and gait parameters.

PMID- 15959854
TI  - A new deletion in autosomal dominant guanosine triphosphate cyclohydrolase I
      deficiency gene--Segawa disease.
AB  - Hereditary Progressive Dystonia with marked diurnal fluctuation (HPD) is an
      autosomally dominantly inherited dystonia which is characterized by marked
      diurnal fluctuation of symptoms and by marked and sustained response to levodopa
      associated with mutations in guanosine triphosphate cyclohydrolase (GCH-1)
      deficiency gene. We report an italian patient with a new 18 bp deletion at 267 in
      exon 1 in the GCH-1 gene. The peculiarity of our patient is the new mutations
      never reported and mnemonic disturbances that are also not reported in the
      classical HPD.A genotype-phenotype relationship may be suggested between
      different gene mutations and non classical clinical manifestations.

PMID- 15959853
TI  - Effects of selegiline on antioxidant systems in the nigrostriatum in rat.
AB  - Selegiline, a therapeutic agent of Parkinson's disease, is known to have
      neuroprotective properties that may involve its regulatory effects on antioxidant
      enzymes. We evaluated effects of selegiline on activities of catalase (CAT),
      Cu,Zn-superoxide dismutase (SOD1) and Mn-SOD (SOD2) in the striatum, cortex and
      hippocampus of 8- and 25-week-old rats, and on SOD activities and glutathione
      levels in mesencephalic slice cultures. Selegiline (2 mg/kg) significantly
      increased CAT and SOD2 activities in the striatum, but not in the cortex and
      hippocampus, of 25-week-old rats. In contrast, selegiline failed to increase CAT
      and SOD activities in three brain regions of 8-week-old rats, whereas L: -dopa
      significantly increased SOD1 activity in the striatum. In slice cultures,
      selegiline increased SOD1 and SOD2 activities with a maximal effective
      concentration of 10(-8) and 10(-10) M, respectively. Moreover, selegiline
      significantly increased glutathione level. These results suggest that selegiline
      can decrease oxidative stress in nigrostriatum by augmenting various antioxidant
      systems, each of which responds optimally to different concentrations of
      selegiline.

PMID- 15959855
TI  - Platelet monoamine oxidase B (MAO-B) activity and its relationship to DL
      fenfluramine-induced prolactin response in healthy men.
AB  - Several techniques are used to assess central serotonergic neurotransmission in
      man, e.g. challenge tests (hormonal and physiological responses to serotonin
      active drugs), platelet MAO-B activity as well as brain imaging techniques.
      Little is known about how these tests relate to each other. The aim of the
      present study was therefore to investigate if platelet MAO-B activity could be
      related to hormonal and temperature responses to the serotonin active drug DL
      fenfluramine in healthy men. Twelve male subjects without any history of
      psychiatric disorders or drug abuse/dependencies were recruited. Prior to the
      challenge with 60 mg DL-fenfluramine, which was given orally, blood for
      determination of platelet MAO-B activity was drawn. Blood samples for
      determination of serum prolactin and serum cortisol were drawn at baseline and
      thereafter every hour for the following six hours. In addition, body temperature
      was measured at the same time-points. Delta-values were calculated as the
      difference between the baseline values and the highest (prolactin and cortisol)
      or lowest value (temperature) thereafter. There was a strong positive correlation
      (r = 0.75, p < 0.02) between platelet MAO-B activity and Delta-prolactin. No
      correlations were found to Delta-cortisol, Delta-temperature or any of the
      baseline values. The results support the notion that the peripheral marker
      platelet MAO-B activity is related to the function of the central serotonergic
      neurotransmitter system as assessed by the prolactin response to 60 mg DL
      fenfluramin.

PMID- 15959856
TI  - Activation of glycogen synthase kinase-3 induces Alzheimer-like tau
      hyperphosphorylation in rat hippocampus slices in culture.
AB  - Formation of neurofibrillary tangle from hyperphosphorylated tau is one of the
      hallmark lesions seen in Alzheimer's disease (AD) brain, and neuronal
      deregulation of glycogen synthase kinase-3 (GSK-3) activity plays key role in tau
      hyperphosphorylation. In the present study, the role of GSK-3 on tau
      phosphorylation in hippocampus slice culture was examined by incubating the slice
      with wortmannin (WT), an inhibitor of phosphatidylinositol 3-kinase (PI3K) and GF
      109203X (GFX), an inhibitor of protein kinase C (PKC). It was found that
      treatment of the slices with GFX or WT separately induced tau
      hyperphosphorylation both at Ser396/Ser404 (PHF-1) and Ser199/Ser202 (Tau-1)
      sites. The phosphorylation rate of tau at PHF-1 and Tau-1 epitopes was further
      increased when GFX and WT were used in combination, and at this condition, AD
      like tau accumulation was observed. GSK-3 activity was significantly increased
      with a concurrently decreased level of inactivated form of GSK-3. Lithium
      chloride (LiCl), a GSK-3 inhibitor, prevented tau from WT- and GFX-induced
      hyperphosphorylation. It suggests that GSK-3 is regulated through PI3K and PKC
      pathway, and activation of GSK-3 not only induces hyperphosphorylation of tau but
      also leads to accumulation of tau in cultured rat brain slice.

PMID- 15959857
TI  - A prospective study of serum ghrelin levels in patients treated with clozapine.
AB  - We investigated serum ghrelin levels (SGL) in 12 patients with schizophrenia over
      a 10-week period after initiation of clozapine treatment. In contrast to
      increments of body mass indices (BMI, kg/m2) and serum leptin levels (SLL), no
      significant change in SGL was detected. Inverse correlations between delta SGL
      and delta SLL did not reach statistical significance. Linear mixed model analysis
      could not detect effects of age, sex, BMI, SLL and serum clozapine levels on SGL.
      Our results do not support a causal involvement of ghrelin in clozapine-related
      weight gain.

PMID- 15959858
TI  - Effect of awake Carotid Endarterectomy under local anaesthesia on peri-operative
      blood pressure: blood pressure is normalised when carotid stenosis is treated
      under local anaesthesia.
AB  - BACKGROUND: Carotid Endarterectomy can be performed under local, regional or
      general anaesthesia. One of the most important effects of the type of anaesthetic
      used is on the systemic blood pressure. Although variations in blood pressure
      during and following carotid endarterectomy have been studied previously, the
      effects of awake carotid endarterectomy under local anaesthesia on blood pressure
      and its comparison with similar procedures under similar types of anaesthesia
      have not. METHODS: Peri-operative blood pressure measurements were collected from
      the records of 25 consecutive patients for each of the following five procedures;
      Carotid Endarterectomy under general anaesthesia (CEAGA), Anterior Cervical
      Discectomy and Fusion under general anaesthesia (ACDF), Cerebral Angiography
      under local anaesthesia (ANG), Carotid Endarterectomy patients under local
      anaesthesia who were symptomatic (CEALAS) and Carotid Endarterectomy patients
      under local anaesthesia who were asymptomatic (CEALAA). The recordings were then
      analysed to find out if there were any clinically significant variations in peri
      operative blood pressure. FINDINGS: There is a significant and consistent
      difference when the pre-operative value was compared with the 4 hour and 24 hour
      post-operative recordings between the local and general anaesthetic groups for
      carotid endarterectomy. Carotid endarterectomy reduces the systolic and diastolic
      blood pressures post-operatively when performed under local anaesthesia and only
      the diastolic pressure was reduced when performed under general anaesthesia.
      CONCLUSION: The study provides evidence about the effect of carotid
      endarterectomy on the systemic blood pressure and its variations when performed
      under different types of anaesthesia. There is significant post-operative
      reduction in both the systolic and diastolic blood pressure values and the
      intraoperative fluctuation is minimal when local anaesthesia is used. Further
      studies are required to find out how this affects the long-term blood pressure
      and clinical outcome of the patient.

PMID- 15959859
TI  - Single nucleotide variants in the beta2-adrenergic and beta3-adrenergic receptor
      genes explained 18.3% of adolescent obesity variation.
AB  - Associations of obesity with its candidate genes, beta-adrenergic receptor genes
      (ADRBs), peroxisome proliferator-activated receptor-gamma (PPARgamma), and
      uncoupling proteins (UCPs) were studied in Korean adolescents. We analyzed the
      obesity-related phenotypes body mass index (BMI), percentage of body fat, plasma
      leptin and insulin levels, fasting glucose concentration, and plasma lipid
      profile in 329 teenagers to investigate the effects of seven single nucleotide
      variants 252G/A, 523C/A and 1053G/C in ADRB2; Trp64Arg in ADRB3; 161C/T in
      PPARgamma; Ala55Val in UCP2; and 210C/T in UCP3. The 1053G/C polymorphism (P <
      0.05) in the ADRB2 gene and the Trp64Arg polymorphism (P < 0.01) in the ADRB3
      gene were associated with BMI after adjustment for dietary energy intake.
      Trp64Arg polymorphism also influenced percentage of body fat (P < 0.01) and
      plasma leptin level (P < 0.05). Furthermore, significant interaction effects
      between the 1053G/C and Trp64Arg polymorphisms were observed on BMI (P < 0.01).
      The polymorphisms of the ADRB2 and ADRB3 genes explained 4.3% and 10.1% of the
      variation on BMI, and the two loci effect, including their epistasis, explained
      18.3%. We concluded that 1053G/C and Trp64Arg polymorphisms of the ADRB genes
      additively and interactively contributed to the variation of complex adolescent
      obesity.

PMID- 15959860
TI  - Silyl anions or silylenoids?--A DFT study of silyllithium compounds with pi
      donating substituents.
AB  - Geometry optimizations at the B3LYP/6-31 + G(d) level for a set of X(SiH3)MeSiLi
      molecules (X = F, OH, NH2, Cl, SH, and PH2) show that the tetrahedral structure
      prevails in polar solutions; however, it readily isomerizes into a silylenoid
      with energy barriers of less than 15 kJ mol(-1). Inverted structures, which
      predominate in the gas phase, could not be located in solution. Configuration
      inversion is unfavorable, with energy barriers between 80 and 220 kJ mol(-1). The
      alpha elimination into a silylene moiety and the corresponding LiX is only likely
      to occur in solution, particularly for X = Cl and SH.

PMID- 15959861
TI  - Diastereoselective synthesis of five- and seven-membered rings by [2+2+1], [3+2],
      [3+2+2], and [4+3] carbocyclization reactions of beta-substituted
      (alkenyl)(methoxy)carbene complexes with methyl ketone lithium enolates.
AB  - beta-Substituted alkenylcarbene complexes react with methyl ketone lithium
      enolates to give different carbocyclization products depending on the structure
      of the lithium enolate, on the metal of the carbene complex, and on the reaction
      media. Thus, the reactions of aryl and alkyl methyl ketone lithium enolates with
      beta-substituted alkenyl chromium and tungsten carbene complexes in diethyl ether
      afford 1,3-cyclopentanediol derivatives derived from a formal [2+2+1]
      carbocyclization reaction. However, the lithium enolates of acetone and tungsten
      complexes furnish formal [3+2+2] carbocyclization products. In the case of
      alkynyl methyl ketone lithium enolates, competitive formal [2+2+1] and [3+2]
      carbocyclization reactions occur and 1,3-cyclopentanediol and 3-cyclopentenol
      derivatives are formed. Conversely, alkenyl methyl ketone lithium enolates react
      with alkenylcarbene complexes under the same reaction conditions to form 2
      cycloheptenone derivatives by a formal [4+3] carbocyclization reaction. Finally,
      when the reaction was performed in the presence of a coordinating medium, the
      [3+2] carbocyclization pattern was observed independently of the nature of the
      methyl ketone lithium enolate used.

PMID- 15959862
TI  - Self-assembled pentamers and hexamers linked through quadruple-hydrogen-bonded 2
      ureido-4[1H]-pyrimidinones.
AB  - The preorganization of bifunctional 2-ureido-4-pyrimidinones mediated by either
      1,3-substituted adamantane or meta-substituted phenylene ring linkers leads to
      the preferred formation of stable pentameric (1)(5) and hexameric (2)(6)
      assemblies, respectively. Despite the high binding constant of the 2-ureido-4
      pyrimidinone dimers and the highly preorganized structure of the monomer, the
      predominant formation of cycles (1)(5) and (2)(6) in solution occurs only within
      a specific concentration range.

PMID- 15959863
TI  - Single-crystalline iron oxide nanotubes.

PMID- 15959864
TI  - A free-running DNA motor powered by a nicking enzyme.

PMID- 15959865
TI  - Conditioning stimulus can influence an external urethral sphincter contraction
      evoked by a magnetic stimulation.
AB  - AIMS: To study the effect of a conditioning stimulus on an external urethral
      sphincter (EUS)contraction evoked by a magnetic stimulation at different time
      intervals. METHODS: Seven healthy male volunteers underwent EUS pressure
      measurement. At baseline, magnetic stimulation of the lumbosacral spinal cord
      above the motor threshold was performed and evoked EUS pressure responses were
      recorded. The lumbosacral magnetic stimulation was repeated with same intensity,
      while a selective electrical dorsal penile nerve stimulation below the
      bulbocavernosus reflex (BCR) threshold was preceding at five different intervals
      (10, 20, 30, 50, 100 msec). The protocol was performed with empty and full
      bladder (BLA), and baseline responses were statistically compared to those with
      combined stimulation. RESULTS: When the dorsal penile nerve electrical
      stimulation preceded the lumbosacral magnetic stimulation by 20 msec (P=0.0048),
      50 msec (P=0.0039), or 100 msec (P=0.0002), the amplitudes of the EUS pressure
      response with empty BLA were significantly reduced compared to lumbosacral
      magnetic stimulation alone. With a filled BLA, the amplitudes of the EUS were
      significantly reduced only at an interval of 50 msec (P<0.0001). CONCLUSIONS: A
      conditional sensory pudendal stimulation seems to have the capacity to inhibit
      the external urethral sphincter contraction induced by a magnetic stimulation.
      The inhibitory effect seems to depend on the latency between the peripheral and
      lumbosacral stimulation as well as on the degree of BLA filling. It remains to be
      proved if the neuromodulative effect of the conditional stimulus occurs at a
      spinal or supraspinal level.

PMID- 15959868
TI  - Simultaneous determination of ten amphetamine designer drugs in human whole blood
      by capillary electrophoresis with diode array detection.
AB  - In recent years, a number of new designer drugs have entered the illicit drug
      market. The methylenedioxyderivatives of amphetamine represent the largest group
      of designer drugs. This paper describes a method for screening for and
      simultaneously quantifying 10 2,5-methylenedioxy-derivatives of amphetamine and
      phenethylamine in human whole blood, using capillary electrophoresis (CE) with
      diode array detection (DAD). Using an aqueous pH 2.5 phosphate buffer, CE
      analysis gave peaks with good symmetry and reproducible migration times. Under
      these experimental conditions, the 10 amphetamines were resolved in 15 min and
      without interference from biological matrices (blood). Their identification by
      migration time was confirmed by their UV spectra recorded with a DAD (190-350
      nm). The main advantages of the present method lie in its simplicity, clean and
      reliable extraction from human whole blood and simultaneous detection and
      quantification by CE-DAD. The applicability of the method was demonstrated by
      analysis of in vivo rat blood samples. The method was validated according to
      international guidelines.

PMID- 15959866
TI  - Long dynamics simulations of proteins using atomistic force fields and a
      continuum representation of solvent effects: calculation of structural and
      dynamic properties.
AB  - Long dynamics simulations were carried out on the B1 immunoglobulin-binding
      domain of streptococcal protein G (ProtG) and bovine pancreatic trypsin inhibitor
      (BPTI) using atomistic descriptions of the proteins and a continuum
      representation of solvent effects. To mimic frictional and random collision
      effects, Langevin dynamics (LD) were used. The main goal of the calculations was
      to explore the stability of tens-of-nanosecond trajectories as generated by this
      molecular mechanics approximation and to analyze in detail structural and
      dynamical properties. Conformational fluctuations, order parameters, cross
      correlation matrices, residue solvent accessibilities, pKa values of titratable
      groups, and hydrogen-bonding (HB) patterns were calculated from all of the
      trajectories and compared with available experimental data. The simulations
      comprised over 40 ns per trajectory for ProtG and over 30 ns per trajectory for
      BPTI. For comparison, explicit water molecular dynamics simulations (EW/MD) of 3
      ns and 4 ns, respectively, were also carried out. Two continuum simulations were
      performed on each protein using the CHARMM program, one with the all-atom PAR22
      representation of the protein force field (here referred to as PAR22/LD
      simulations) and the other with the modifications introduced by the recently
      developed CMAP potential (CMAP/LD simulations). The explicit solvent simulations
      were performed with PAR22 only. Solvent effects are described by a continuum
      model based on screened Coulomb potentials (SCP) reported earlier, i.e., the SCP
      based implicit solvent model (SCP-ISM). For ProtG, both the PAR22/LD and the
      CMAP/LD 40-ns trajectories were stable, yielding C(alpha) root mean square
      deviations (RMSD) of about 1.0 and 0.8 A respectively along the entire simulation
      time, compared to 0.8 A for the EW/MD simulation. For BPTI, only the CMAP/LD
      trajectory was stable for the entire 30-ns simulation, with a C(alpha) RMSD of
      approximately 1.4 A, while the PAR22/LD trajectory became unstable early in the
      simulation, reaching a C(alpha) RMSD of about 2.7 A and remaining at this value
      until the end of the simulation; the C(alpha) RMSD of the EW/MD simulation was
      about 1.5 A. The source of the instabilities of the BPTI trajectories in the
      PAR22/LD simulations was explored by an analysis of the backbone torsion angles.
      To further validate the findings from this analysis of BPTI, a 35-ns SCP-ISM
      simulation of Ubiquitin (Ubq) was carried out. For this protein, the CMAP/LD
      simulation was stable for the entire simulation time (C(alpha) RMSD of
      approximately 1.0 A), while the PAR22/LD trajectory showed a trend similar to
      that in BPTI, reaching a C(alpha) RMSD of approximately 1.5 A at 7 ns. All the
      calculated properties were found to be in agreement with the corresponding
      experimental values, although local deviations were also observed. HB patterns
      were also well reproduced by all the continuum solvent simulations with the
      exception of solvent-exposed side chain-side chain (sc-sc) HB in ProtG, where
      several of the HB interactions observed in the crystal structure and in the EW/MD
      simulation were lost. The overall analysis reported in this work suggests that
      the combination of an atomistic representation of a protein with a CMAP/CHARMM
      force field and a continuum representation of solvent effects such as the SCP-ISM
      provides a good description of structural and dynamic properties obtained from
      long computer simulations. Although the SCP-ISM simulations (CMAP/LD) reported
      here were shown to be stable and the properties well reproduced, further
      refinement is needed to attain a level of accuracy suitable for more challenging
      biological applications, particularly the study of protein-protein interactions.

PMID- 15959871
TI  - Current literature in diabetes.

PMID- 15959869
TI  - Liquid chromatography-tandem mass spectrometry for the identification of L
      tetrahydropalmatine metabolites in Penicillium janthinellum and rats.
AB  - L-tetrahydropalmatine (L-THP) is an active alkaloid from Stephania ainiaca Diels.
      In order to compare the similarities and differences of microbial and mammalian
      metabolisms of L-THP, the microbial transformation by Penicillium janthinellum
      and metabolism in rats were investigated. Biotransformation of L-THP by
      Penicillium janthinellum AS 3.510 resulted in the formation of three metabolites.
      Their structures were identified as L-corydalmine, L-corypalmine and 9-O
      desmethyl-L-THP, respectively, by comprehensive nuclear magnetic resonance and
      mass spectrometry (MS) analysis. Six metabolites (M1-M6) were detected from the
      in vivo study in rats and three of which (L-corydalmine, L-corypalmine and 9-O
      desmethyl-L-THP) were identified as the same compounds as those obtained from
      microbial metabolism by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      analysis and comparison with reference standards obtained from microbial
      metabolism. The structures of the additional three metabolites were tentatively
      deduced as 2-O-desmethyl-L-THP and two di-O-demethylated L-THP by LC-MS/MS
      analysis. Time courses of microbial and rat metabolisms of L-THP were also
      investigated.

PMID- 15959872
TI  - Use of vascularized iliac crest with internal oblique muscle flap for mandible
      reconstruction.
AB  - In the last decade, immediate reconstruction of maxillary bones following
      extensive trauma, large oncological defects, or late effects of radiation therapy
      has proved to be a reliable morpho-functional reconstruction technique. Use of
      the vascularized iliac crest with an internal oblique flap has become our flap of
      choice for mandible reconstruction when there is no need for overlying facial
      skin or oral sphincter reconstruction, and for bone segments within 6-15 cm of
      length. The advantages of this composite bone flap are the large and resizable
      bone stock available, the quality of bone transferred with an optimal height,
      depth, and contour of bone to maintain a good facial profile, and the possibility
      to reconstruct properly the oral lining, with a portion of the internal oblique
      muscle flap raised with the same pedicle that epithelializes during the healing
      stages. We present the experience of the Department of Maxillofacial Surgery of
      "S. Maria della Misericordia" Regional Hospital in Udine, Italy.

PMID- 15959873
TI  - Twenty-six novel EFNB1 mutations in familial and sporadic craniofrontonasal
      syndrome (CFNS).
AB  - Craniofrontonasal syndrome (CFNS) is an X-linked disorder characterized by a more
      severe manifestation in heterozygous females than in hemizygous males.
      Heterozygous females have craniofrontonasal dysplasia (CFND) and occasionally
      extracranial manifestations including midline defects and skeletal abnormalities,
      whereas hemizygous males show no or only mild features such as hypertelorism and
      rarely show cleft lip or palate. Mutations in the EFNB1 gene in Xq12 are
      responsible for familial and sporadic CFNS. The EFNB1 gene encodes ephrin-B1, a
      transmembrane ligand that also exhibits receptor-like effects. We performed
      mutation analysis in nine unrelated families and 29 sporadic patients with CFNS.
      DNA sequencing revealed mutations in 33 (86.8%) cases including 26 distinct novel
      mutations. A recurrent nonsense mutation, c.196C>T/R66X, was detected in one
      family and four sporadic patients. The majority of mutations (26/33) were located
      in exons 2 and 3 of the EFNB1 gene encoding the extracellular ephrin domain. The
      mutation spectrum includes frameshift, nonsense, missense, and splice site
      mutations, with a predominance of frameshift and nonsense mutations resulting in
      premature truncation codons. For the first time we describe mutations in exons 4
      and 5 of EFNB1. Of particular interest are the frameshift mutations located in
      the last 25 codons of EFNB1 encoding the carboxyterminal end of ephrin-B1. They
      result in an extension by 44 residues. These mutations disrupt the intracellular
      binding sites for Grb4 and PDZ-effector proteins involved in reverse signaling.
      We conclude that the major causes of familial as well as sporadic CFNS are loss
      of function mutations in the EFNB1 gene that comprise premature termination or
      abrogate receptor-ligand interaction, oligomerization, and ephrin-B1 reverse
      signaling.

PMID- 15959874
TI  - Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in
      vivo mouse model.
AB  - BACKGROUND: Fumonisin B1 (FB1) is a mycotoxin produced by the fungus Fusarium
      verticillioides, a common contaminant of corn worldwide. FB1 disrupts
      sphingolipid biosynthesis by inhibiting the enzyme ceramide synthase, resulting
      in an elevation of free sphingoid bases and depletion of downstream
      glycosphingolipids. A relationship between maternal ingestion of FB1-contaminated
      corn during early pregnancy and increased risk for neural tube defects (NTDs) has
      recently been proposed in human populations around the world where corn is a
      dietary staple. The current studies provide an in vivo mouse model of FB1
      teratogenicity. METHODS: Pregnant LM/Bc mice were injected with increasing doses
      of FB1 on GD 7.5 and 8.5, and exposed fetuses were examined for malformations.
      Sphingolipid profiles and (3)H-folate concentrations were measured in maternal
      and fetal tissues. Immunohistochemical expression of the GPI-anchored folate
      receptor (Folbp1) and its association with the lipid raft component, ganglioside
      GM1, were characterized. Rescue experiments were performed with maternal folate
      supplementation or administration of gangliosides. RESULTS: Maternal FB1
      administration (20 mg/kg of body weight) during early gestation resulted in 79%
      NTDs in exposed fetuses. Sphingolipid profiles were significantly altered in
      maternal and embryonic tissues following exposure, and (3)H-folate levels and
      immunohistochemical expression of Folbp1 were reduced. Maternal folate
      supplementation partially rescued the NTD phenotype, whereas GM1 significantly
      restored folate concentrations and afforded almost complete protection against
      FB1-induced NTDs. CONCLUSIONS: Maternal FB1 exposure altered sphingolipid
      metabolism and folate concentrations in LM/Bc mice, resulting in a dose-dependent
      increase in NTDs that could be prevented when adequate folate levels were
      maintained.

PMID- 15959875
TI  - Antioxidative treatment of pregnant diabetic rats diminishes embryonic
      dysmorphogenesis.
AB  - BACKGROUND: Diabetic pregnancy is still associated with an increased rate of
      congenital malformations despite extensive clinical efforts to normalize the risk
      for the offspring. The etiology of diabetic embryopathy is not clear; however,
      experimental studies have suggested a role for oxidative stress in the
      teratogenicity of diabetic pregnancy. The antioxidants alpha-tocopherol and
      ascorbate have improved fetal outcome in diabetic rodent pregnancy when
      supplemented in moderate to high doses. In the present work we investigated if
      extremely high doses of either alpha-tocopherol or ascorbate might further
      improve fetal outcome in offspring of diabetic rats and, in addition, if such
      treatment may exert any adverse effects of fetal development. METHODS:
      Nondiabetic and streptozotocin diabetic female rats were fed 2, 5, 10, or 15%
      alpha-tocopherol or 4, 10, or 15% ascorbate in their diet. RESULTS: Both alpha
      tocopherol and ascorbate treatment improved fetal morphology in offspring of
      diabetic rats. There was a dose-dependent improvement for the alpha-tocopherol
      supplementation, in which the higher doses diminished fetal dysmorphogenesis more
      than the 2% diet. The ascorbate supplementation was less dose-dependent; however,
      the higher doses tended to improve fetal outcome more than the lower doses. No
      adverse effects of the antioxidants were noted in the offspring with the
      exception of 1 case of agnathia in a fetus of a nondiabetic rat supplemented with
      15% alpha-tocopherol. CONCLUSIONS: These results indicate that very high doses of
      dietary antioxidants may be needed to normalize the development of the offspring
      in experimental diabetic pregnancy, but that treatment with such high doses may
      also have adverse effects in nondiabetic pregnancy.

PMID- 15959876
TI  - A diabetes-like environment increases malformation rate and diminishes
      prostaglandin E(2) in rat embryos: reversal by administration of vitamin E and
      folic acid.
AB  - BACKGROUND: Offspring of women with diabetes are at increased risk for congenital
      malformations and disturbed growth compared with infants from nondiabetic
      pregnancies. The precise biological process behind these effects is not yet
      completely clarified. Previous studies have suggested that diabetic embryopathy
      is associated with increased level of oxidative stress and disturbed arachidonic
      acid metabolism. The aim of the present study was to investigate whether a
      diabetes-like environment both in vivo and in vitro increases embryonic levels of
      isoprostanes and alters embryonic prostaglandin E(2) (PGE(2)) concentration.
      Furthermore, we studied whether vitamin E and folic acid treatment rectify such
      alterations. METHODS: Embryos from diabetic and nondiabetic rats at gestational
      days (GDs) 10 and 11 were used. In the in vitro experiments, we used whole embryo
      culture, which mimics pregnancy. GD 9 embryos from nondiabetic rats were cultured
      for either 24 hr (corresponding to GD 10) or 48 hr (corresponding to GD 11) and
      exposed to 10 or 30 mM glucose concentration with or without folic acid. RESULTS:
      Embryos from diabetic rats and embryos cultured in a high glucose concentration
      showed increased malformation rates. Dietary treatment with vitamin E in vivo and
      supplementation of folic acid in the culture medium with 30 mM glucose in vitro
      decreased the malformation rate, decreased embryonic isoprostane levels, and
      increased PGE(2) concentration. CONCLUSIONS: Diabetes-induced oxidative stress
      and disturbance of PGE(2) production may contribute to the embryonic
      dysmorphogenesis in the offspring of diabetic rodents and, thereby, may also have
      a role in human diabetic embryopathy.

PMID- 15959878
TI  - A teratoproteomics analysis: heat shock protein 70 is upregulated in mouse
      forelimb bud by methoxyacetic acid treatment.
AB  - BACKGROUND: Methoxyacetic acid (MAA) causes fetal limb abnormalities when the
      substance is administrated on gestation day (GD) 11 in mice. Limb abnormalities
      are caused mainly by extensive cell death in the mesoderm of the limb plate. This
      investigation focused on identifying a protein that is linked with mouse limb
      teratogenicity. METHODS: A single dose of MAA at 10 mmol/kg body weight was
      administered by gavage on GD 11; controls were administered vehicle only. Dams
      were killed by cervical dislocation 4 hr after treatment and forelimb buds were
      isolated from both the control and treated embryos. Proteins in forelimb buds GD
      11 + 4 hr were precipitated out using 40-60% ammonium sulfate and were then
      analyzed by 2D SDS-PAGE. Excised protein spots were identified by mass
      spectrometry and amino acid internal sequence analysis. Identified protein was
      further confirmed by Western blotting. RESULTS: Two-dimensional gel analysis
      indicated that 1 protein spot of 81.7 kDa/pI 7.3 was overexpressed, and the
      protein matched heat shock protein 70 (HSP70; accession no. P08109, SwissProt).
      CONCLUSIONS: The results suggest that MAA, when administered to pregnant mice,
      upregulates HSP70 in the forelimb buds.

PMID- 15959877
TI  - The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk
      of spina bifida.
AB  - BACKGROUND: The risk of having a child with a neural tube defect (NTD) can be
      reduced by maternal, periconceptional supplementation with folic acid, but the
      underlying folate-dependent protective mechanism remains unclear. N
      acetyltransferase 1 is involved in acetylation of aromatic and heterocyclic
      amines and the catabolism of folates. Hence, functional polymorphisms in NAT1,
      the gene encoding N-acetyltransferase 1, are plausible risk factors for NTDs.
      Such variants could exert an influence on the risk of NTDs via their role in
      acetylation or folate catabolism and could act through the maternal or the
      embryonic genotype. METHODS: NAT1 C1095A genotypes and information on maternal,
      periconceptional multivitamin use and smoking were obtained as part of a family
      based study of spina bifida. Associations between spina bifida and the embryonic
      and maternal NAT1 C1095A genotypes, and potential NAT1 C1095A genotype-exposure
      interactions were evaluated using log-linear modeling. RESULTS: The analyses
      provided no evidence that the embryonic or maternal NAT1 C1095 genotypes
      influence the risk of spina bifida independently, or through interactions with
      maternal use of multivitamins. There was evidence that the embryonic, and
      possibly the maternal, NAT1 C1095A genotype influence the risk of spina bifida
      via interactions with maternal smoking status. CONCLUSIONS: The genotype for the
      NAT1 C1095A polymorphism does not appear to be an independent risk factor for
      spina bifida. However, the results of these analyses provide preliminary evidence
      that this polymorphism may be associated with the risk of spina bifida in the
      offspring of women who smoke during early pregnancy.

PMID- 15959879
TI  - Potential limitations of electronic database studies of prescription non-aspirin
      non-steroidal anti-inflammatory drugs (NANSAIDs) and risk of myocardial
      infarction (MI).
AB  - PURPOSE: To determine whether specific limitations in electronic database studies
      may lead to biased estimates of the association between prescription, non
      selective non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) and
      myocardial infarction (MI) METHODS: Using our case-control study of NANSAIDs and
      first, non-fatal MI, we determined the odds ratio (OR) for prescription NANSAIDs
      and MI. In the 'Replicating Electronic Database Analysis,' we considered non
      prescription NANSAID users to be 'non-users,' did not stratify by aspirin use,
      and did not adjust for confounders typically unavailable or incomplete in
      existing databases. In the 'Misclassification Assessment Analysis,' we removed
      non-prescription NANSAIDs from the 'non-user' category. In the 'Confounding
      Assessment Analysis #1,' we additionally adjusted for smoking, family history,
      and years of education. In the 'Confounding Assessment Analysis #2,' we also
      adjusted for body mass index (BMI) and physical activity. In the 'Interaction
      Assessment Analysis,' we stratified on aspirin use and repeated the latter
      analysis. RESULTS: The prevalence of current NANSAID and aspirin use was higher
      in our controls than in electronic database studies, consistent with the fact
      that non-prescription NANSAIDs accounted for 81% of all NANSAID use. Education,
      physical activity, and BMI also were associated with prescription NANSAID use.
      When each potential source of bias was removed, the OR for NANSAIDs moved further
      from 1.0 (i.e., toward a protective association with MI): 'Replicating Electronic
      Database' analysis (OR 1.00, 95% confidence interval [CI]: 0.78--1.28);
      'Misclassification Assessment Analysis' (OR 0.89, 95%CI: 0.70--1.14);
      'Confounding Assessment Analysis #1' (OR 0.85, 95%CI: 0.66--1.10); 'Confounding
      Assessment Analysis #2' (OR 0.78, 95%CI: 0.60--1.01); 'Interaction Assessment
      Analysis' (OR 0.69, 95%CI: 0.51--0.95). CONCLUSIONS: Limitations in electronic
      databases may be responsible for the lack of association of NANSAIDs on lower MI
      risk noted in these studies. Further studies-preferably randomized trials-are
      needed to address the risk-benefit ratio of NANSAID use.

PMID- 15959880
TI  - Practical aspects of sharing controls between case-control studies.
AB  - PURPOSE: We discuss the practical advantages and challenges of sharing controls
      among two or more concurrently conducted case-control studies. METHODS: We
      conducted two case-control studies, one of breast cancer and the other of
      endometrial cancer, with overlapping, shared control groups. The studies had
      overlapping geographic areas, identical telephone questionnaires and biosample
      collection, and identical age and race eligibility. RESULTS: Sharing controls
      reduced the number of potential controls that had to be identified by random
      digit dialing by 25% and the number of eligible controls that had to be
      interviewed by 32%. The cost savings were approximately 2,96,000 dollars, or 7%
      of the program project that funded the studies. CONCLUSIONS: The disadvantage of
      sharing controls was the complexity of the design and the additional investigator
      time required to plan, monitor, and adjust the design. In the situation presented
      here, the complexities would have been reduced greatly if we had not attempted to
      frequency match on age in both studies. Generally, sharing controls is likely to
      work well when strict frequency matching is not required and there is a large
      overlap of interview questions, other data to be collected, and eligibility
      criteria among the studies.

PMID- 15959881
TI  - Biowaiver monographs for immediate release solid oral dosage forms: ranitidine
      hydrochloride.
AB  - Literature and experimental data relevant to the decision to allow a waiver of in
      vivo bioequivalence testing for the approval of immediate release (IR) solid oral
      dosage forms containing ranitidine hydrochloride are reviewed. According to the
      current Biopharmaceutics Classification System (BCS), ranitidine hydrochloride
      should be assigned to Class III. However, based on its therapeutic and
      therapeutic index, pharmacokinetic properties and data related to the possibility
      of excipient interactions, a biowaiver can be recommended for IR solid oral
      dosage forms that are rapidly dissolving and contain only those excipients as
      reported in this study.

PMID- 15959882
TI  - Glycoengineering: the effect of glycosylation on the properties of therapeutic
      proteins.
AB  - Therapeutic proteins have revolutionized the treatment of many diseases but low
      activity or rapid clearance limits their utility. New approaches have been taken
      to design drugs with enhanced in vivo activity and half-life to reduce injection
      frequency, increase convenience, and improve patient compliance. One recently
      used approach is glycoengineering, changing protein-associated carbohydrate to
      alter pharmacokinetic properties of proteins. This technology has been applied to
      erythropoietin and resulted in the discovery of darbepoetin alfa (DA), a
      hyperglycosylated analogue of erythropoietin that contains two additional N
      linked carbohydrates, a threefold increase in serum half-life and increased in
      vivo activity compared to recombinant human erythropoietin (rHuEPO). The
      increased serum half-life allows for less frequent dosing to maintain target
      hemoglobin levels in anemic patients. Carbohydrates on DA and other molecules can
      also increase molecular stability, solubility, increase in vivo biological
      activity, and reduce immunogenicity. These properties are discussed.

PMID- 15959883
TI  - Overview of clinical perspectives and mechanisms of obesity.

PMID- 15959884
TI  - Developmental origins and environmental influences--Introduction. NIEHS
      symposium.

PMID- 15959885
TI  - Effects of estrogens and the phytoestrogen genistein on adipogenesis and
      lipogenesis in males and females.

PMID- 15959886
TI  - Commercial animal feed: variability in estrogenic activity and effects on body
      weight in mice.

PMID- 15959887
TI  - From multipotent stem cell to adipocyte.

PMID- 15959888
TI  - Developmental exposure to estrogenic compounds and obesity.

PMID- 15959889
TI  - Fetal nicotinic overload, blunted sympathetic responsivity, and obesity.

PMID- 15959890
TI  - Birth weight and obesity and fat distribution in later life.

PMID- 15959891
TI  - Tissue engineering of human cartilage in bioreactors using single and composite
      cell-seeded scaffolds.
AB  - Chondrocytes isolated from human fetal epiphyseal cartilage were seeded under
      mixed conditions into 15-mm-diameter polyglycolic acid (PGA) scaffolds and
      cultured in recirculation column bioreactors to generate cartilage constructs.
      After seeding, the cell distributions in thick (4.75 mm) and thin (2.15 mm) PGA
      disks were nonuniform, with higher cell densities accumulating near the top
      surfaces. Composite scaffolds were developed by suturing together two thin PGA
      disks after seeding to manipulate the initial cell distribution before bioreactor
      culture. The effect of medium flow direction in the bioreactors, including
      periodic reversal of medium flow, was also investigated. The quality of the
      tissue-engineered cartilage was assessed after 5 weeks of culture in terms of the
      tissue wet weight, glycosaminoglycan (GAG), total collagen and collagen type II
      contents, histological analysis of cell, GAG and collagen distributions, and
      immunohistochemical analysis of collagen types I and II. Significant enhancement
      in construct quality was achieved using composite scaffolds compared with single
      PGA disks. Operation of the bioreactors with periodic medium flow reversal
      instead of unidirectional flow yielded further improvements in tissue weight and
      GAG and collagen contents with the composite scaffolds. At harvest, the
      constructs contained GAG concentrations similar to those measured in ex vivo
      human adult articular cartilage; however, total collagen and collagen type II
      levels were substantially lower than those in adult tissue. This study
      demonstrates that the location of regions of high cell density in the scaffold
      coupled with application of dynamic bioreactor operating conditions has a
      significant influence on the quality of tissue-engineered cartilage.

PMID- 15959892
TI  - Stable hybridoma cultivation in a pilot-scale acoustic perfusion system: long
      term process performance and effect of recirculation rate.
AB  - Perfusion systems have the possibility to be operated continuously for several
      months. It is important that the performance of the cell retention device does
      not limit the operation time of a perfusion process used in the production of
      active pharmaceutical ingredients. Therefore, the aim of this study was to
      investigate the reliability and long-term stability of an acoustic perfusion
      process using the 200 L/d BioSep. As the BioSep is an external device, it is
      possible that dependent on the recirculation rate nutrient gradients occur in the
      external loop, which could affect the cell metabolism. Therefore, the effect of
      possible nutrient gradients on cell metabolism, viability and productivity was
      studied by varying the recirculation rate. In this study, it is shown that a
      perfusion process using a pilot-scale acoustic cell-retention device (200 L/d) is
      reliable and simple to operate, resulting in a stable 75-day cultivation of a
      hybridoma cell line producing a monoclonal antibody. The recirculation rate had a
      significant effect on the oxygen concentration in the external loop, with oxygen
      being depleted within the cell-retention device at recirculation rates below 6
      m3/m(reactor)3.d (=600 L/d). The oxygen depletion at low circulation rates
      correlated with a slightly increased lactate production rate. For all other
      parameters no effect of the recirculation rate was observed, including cell death
      measured through the release of lactate dehydrogenase and specific productivity.
      A maximum specific productivity of 12 pg/cell.d was reached.

PMID- 15959893
TI  - Production of fuculose-1-phosphate aldolase using operator-repressor titration
      for plasmid maintenance in high cell density Escherichia coli fermentations.
AB  - We report a novel application for the operator-repressor titration (ORT) plasmid
      maintenance system. The ability of ORT to maintain a plasmid during production of
      DNA has been demonstrated previously. In this study, we have used the ORT system
      to maintain a plasmid during high cell density cultivation and expression of a
      recombinant protein. No evidence of plasmid loss was seen during protein
      expression at high cell densities. In addition, the quantity of protein produced
      using this system was similar to traditional plasmid maintenance systems.

PMID- 15959894
TI  - Updating reactivated memories in infancy: II. Time passage and repetition
      effects.
AB  - Previous attempts to modify a reactivated memory by passively exposing infants to
      a novel cue immediately after reactivation were unsuccessful. Presently, we
      examined other conditions in which passive exposure to a novel cue immediately
      after reactivation might modify the memory. In three experiments, sixty-two 3
      month-olds learned to move a distinctive mobile by kicking, forgot the training
      memory, and then received a reminder that reactivated it. Immediately afterward,
      they were passively exposed to a novel mobile. We found that passive exposure to
      novel information could modify reactivated memories that were older or had been
      reactivated before. Although exposure to a novel mobile occasionally produced
      only retroactive interference, memory modification never occurred alone,
      suggesting that response suppression to the original cue is prerequisite for the
      modification of reactivated memories. We propose that memory distortion
      (modification) is not an anomaly but is an adaptive, updating mechanism that
      ensures that behavior will be guided by memories containing contemporaneous
      information.

PMID- 15959895
TI  - Latent inhibition in the developing rat: an examination of context-specific
      effects.
AB  - Latent inhibition (LI) refers to the reduction in conditioned responding when the
      conditioned stimulus (CS) is preexposed prior to CS-unconditioned stimulus
      pairings. Experiment 1a demonstrated that preexposure to an odor CS prior to odor
      shock pairings markedly reduced conditioned freezing in 25-day-old rats; however,
      this LI effect was observed only if odor preexposure and odor-shock pairings
      occurred in the same context (i.e., LI was context-specific at this age). The
      results of Experiment 1b showed that 18-day-olds also exhibited LI, but this
      effect was not context-specific at this age. In Experiment 2, rats were
      preexposed to the odor at 18 days of age and given odor-shock pairings at 25 days
      of age. These rats exhibited context-specific latent inhibition, suggesting that
      18-day-old rats encoded the preexposure context. In Experiment 3, all parameters
      were identical to Experiment 2, with the exception that odor-shock pairings were
      given at approximately PN18 and testing occurred at approximately PN25. These
      rats exhibited latent inhibition at test, but this effect was not context
      specific. The results of this study suggest that (a) PN18 rats can exhibit latent
      inhibition, and (b) the expression of context-specific latent inhibition depends
      on the age at which conditioning occurs.

PMID- 15959896
TI  - Inhibition of ultrasonic vocalizations by beta-adrenoceptor agonists.
AB  - Infant rat ultrasonic vocalizations (USVs) are widely believed to result from the
      induction of an emotional state of anxiety or distress. This perspective,
      however, is not easily reconciled with the demonstration by W. J. Farrell and J.
      R. Alberts 2000 that norepinephrine, a nonselective beta-adrenoceptor agonist
      with anxiogenic properties, inhibits production of USVs. Here, Farrell and
      Alberts' finding was replicated and extended with 12-day-old rats using a
      conventional isolation paradigm. First, treatment with norepinephrine (1 mg/kg)
      significantly inhibited ultrasound production while also increasing body
      temperature. Next, treatment with the beta-2 agonist terbutaline (1 mg/kg) and
      the beta-3 agonist CL-316243 (1 mg/kg), but not the beta-1 agonist dobutamine (1
      mg/kg), inhibited ultrasound production; only CL-316243 increased body
      temperature. The unexpected inhibition of USVs by terbutaline, a potent
      bronchodilator, was replicated using a slightly modified procedure; again, body
      temperature was unaffected by terbutaline administration. In no experiment was
      inhibition of USVs related to changes in motor activity. Altogether, these
      results suggest either that ultrasound production is not a valid indicator of
      anxiety or that anxiety in infant rats is produced by neuropharmacological
      mechanisms that differ fundamentally from those in adults.

PMID- 15959897
TI  - What impairs subitizing in cerebral palsied children?
AB  - The goal of this study was to investigate the factors responsible for the low
      subitizing limit of cerebral palsied (CP) children. For this purpose, 44 CPs were
      tested on two tasks involving the rapid recognition of dot configurations. The
      answer was either a number (subitizing task) or the name of a pattern (pattern
      recognition task). The CPs were compared to controls of the same age. All
      children were evaluated for visual and visuospatial short-term memory. The
      results showed that CPs with a low subitizing limit did not do better with a
      canonical arrangement than the random one, were impaired to the same extent on
      the pattern recognition task as on the subitizing task, and had a short
      visuospatial short-term memory span. These results suggest that the low
      subitizing limit of CPs stems from a (non-number-dependent) lesser capacity to
      perceive a dot configuration as a gestalt. A low subitizing limit was almost
      always associated with a right-hemisphere lesion.

PMID- 15959898
TI  - Updating reactivated memories in infancy: I. Passive- and active-exposure
      effects.
AB  - This study examined the vulnerability of infants' reactivated memories to
      modification. In three experiments, one hundred eight 3-month-olds learned to
      move a distinctive mobile by kicking. After the operant task was forgotten, its
      memory was recovered by a reactivation treatment. Immediately afterward, attempts
      were made to modify the reactivated memory by exposing infants to a novel mobile.
      Exposing the novel mobile immediately after the reactivation treatment did not
      affect the reactivated memory (Experiment 1). When exposure to the novel mobile
      was delayed for 24 hr, the novel mobile temporarily interfered with recognition
      of the original mobile, but did not modify the reactivated memory (Experiment 2).
      Only when the contingency was briefly associated with the novel mobile (an active
      exposure procedure) was the reactivated memory modified (Experiment 3). These
      data reveal that infants' recently reactivated memories are surprisingly
      resistant to updating unless the operant contingency that established the
      original memory accompanies the new information.

PMID- 15959899
TI  - Effects of priming duration on retention over the first 1 1/2 years of life.
AB  - Exposing individuals to an isolated component (a prime) of a prior event
      alleviates its forgetting. Two experiments with 120 human infants between 3 and
      18 months of age determined the minimum duration of a prime that can reactivate a
      forgotten memory and how long the reactivated memory persists. Infants learned an
      operant task, forgot it, were exposed to the prime, and later were tested for
      renewed retention. In Experiment 1, the minimum duration of an effective prime
      decreased logarithmically with age, but was always longer than the duration of a
      mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast
      after a minimum-duration prime as after a full-length one, irrespective of
      priming delay and infant age. These data reveal that the minimum effective prime
      duration psychophysically equates the accessibility of forgotten memories. We
      conclude that priming is perceptually based with effects that are organized on a
      ratio (log) scale.

PMID- 15959900
TI  - A developmental comparison of trace and delay eyeblink conditioning in rats using
      matching interstimulus intervals.
AB  - The effects of conditioning paradigm and interstimulus interval (ISI) were
      evaluated in this study of the development of associative learning in rats. The
      acquisition of classical eyeblink conditioning (EBC) was examined in two
      paradigms (trace vs. delay), with three different ISIs (short, medium, or long)
      at two ages (postnatal Days 21-23 or 29-31). These data provide the first
      parametric analysis of ISI in developing animals trained with trace EBC
      procedures. Further, by comparing trace and delay EBC, it was determined that
      when ISI is held constant, acquisition is similar for both conditioning paradigms
      regardless of developmental age. This suggests a similar ontogeny of associative
      processes for delay and trace EBC that relies on common neural substrates.
      However, conditioned response timing (onset and peak latencies) was affected by
      age and paradigm, suggesting that different neural mechanisms may play a role in
      timing delay versus trace conditioned responses.

PMID- 15959901
TI  - Detection of geometric, but not topological, spatial transformations in 6- to 12
      month-old infants in a visual exploration paradigm.
AB  - Several theories of spatial orientation propose that the geometry of an
      environment plays a privileged role in reorientation, relative to relations
      between individual landmarks. Infants (N = 90) in three age groups (6, 8 1/2, and
      12 months) experienced three conditions: topological, geometric, and control. A
      round room contained four distinctive objects in a rectangular arrangement on the
      inside periphery. Infants were familiarized to the array prior to a 2-min test
      period. In the topological condition, two objects were switched. In the geometric
      condition, the objects were moved to form an irregular quadrilateral. In the
      control condition, the array remained unchanged. Infants of 8 1/2 months and over
      visually explored significantly more in the geometric condition only. An initial
      study with adults found greater visual exploration in both geometric and
      topological conditions. These results are discussed in the context of current
      theories of spatial orientation.

PMID- 15959902
TI  - Lessons from nature: On the molecular recognition elements of the phosphoprotein
      binding-domains.
AB  - The reversible phosphorylation of proteins regulates many biological processes.
      Despite the technological advances in the enrichment and detection of
      phosphorylated proteins, the currently available techniques still struggle with
      the complexity of the human proteome. The aim of this review is to highlight the
      molecular recognition elements of the interaction between phosphorylated proteins
      and peptides and pTyr or pSer/Thr-binding domains. The identification of the
      recognition features of the naturally occurring pTyr- and pSer/Thr-binding
      domains can contribute to an understanding of the molecular aspects of the
      affinity and specificity for phosphorylated residues. This might inspire the
      design of small "biomimetic" molecules with potential applications in assessing
      the extent of the phosphoproteome using affinity-based strategies.

PMID- 15959903
TI  - Microglia function in brain tumors.
AB  - Microglia play an important role in inflammatory diseases of the central nervous
      system (CNS). These cells have also been identified in brain neoplasms; however,
      as of yet their function largely remains unclear. More recent studies designed to
      characterize further tumor-associated microglia suggest that the immune effector
      function of these cells may be suppressed in CNS tumors. Furthermore, microglia
      and macrophages can secrete various cytokines and growth factors that may
      contribute to the successful immune evasion, growth, and invasion of brain
      neoplasms. A better understanding of microglia and macrophage function is
      essential for the development of immune-based treatment strategies against
      malignant brain tumors.

PMID- 15959905
TI  - A restructured framework for modeling oxygen transfer in two-phase partitioning
      bioreactors.
AB  - This communication proposes a mechanistic modification to a recently published
      method for analyzing oxygen mass transfer in two-phase partitioning bioreactors
      (Nielsen et al., 2003), and corrects an oversight in that paper. The newly
      proposed modification replaces the earlier empirical approach, which treated the
      two liquid phases as a single, homogeneous liquid phase, with a two-phase mass
      transfer model of greater fundamental rigor. Additionally, newly developed
      empirical models are presented that predict the mass transfer coefficient of
      oxygen absorption in both aqueous medium and an organic phase (n-hexadecane) as a
      function of bioreactor operating conditions. Experimental values and theoretical
      predictions of mass transfer coefficients in two-phase dispersions, k(L)a(TP),
      are compared. The revised approach more clearly demonstrates the potential for
      oxygen mass transfer enhancement by organic phase addition, one of the
      motivations for employing a distinct second phase in a partitioning bioreactor.

PMID- 15959904
TI  - Microglial cell activation and proliferation precedes the onset of CNS
      autoimmunity.
AB  - Microglial cells are central nervous system (CNS) resident cells that are thought
      to become activated and contribute to the inflammation that occurs in the human
      autoimmune disease multiple sclerosis (MS). This has never been proven, however,
      because microglial cells cannot be phenotypically distinguished from peripheral
      macrophages that accumulate in MS inflammatory lesions. To study the kinetics and
      nature of microglial cell activation in the CNS, we used the animal model of MS,
      experimental autoimmune encephalomyelitis (EAE), and induced EAE in bone marrow
      (BM) chimera mice generated using major histocompatibility complex (MHC)
      mismatched donor BM, allowing the separation of microglial cells and peripheral
      monocytes/macrophages. We found that microglial cell activation was evident
      before onset of disease symptoms and infiltration of peripheral myeloid cells
      into the CNS. Activated microglial cells underwent proliferation and upregulated
      the expression of CD45, MHC class II, CD40, CD86, and the dendritic cell marker
      CD11c. At the peak of EAE disease, activated microglial cells comprised 37% of
      the total macrophage and dendritic cell populations and colocalized with
      infiltrating leukocytes in inflammatory lesions. Our findings thus definitively
      demonstrate that during EAE, microglial cells become activated early in EAE
      disease and then differentiate into both macrophages and dendritic-like cells,
      suggesting they play an active role in the pathogenesis of EAE and MS.

PMID- 15959906
TI  - A cryptic Bacillus isolate exhibited narrow 16S rRNA gene sequence divergence
      with Bacillus thuringiensis and showed low maintenance requirements in hyper
      osmotic complex substrate cultivations.
AB  - A cryptic Bacillus (K90) isolate obtained from soil samples from the Kuwait
      desert exhibited lower maintenance requirements in complex substrate cultivations
      than Bacillus thuringiensis. A mathematical model was used to estimate apparent
      maintenance coefficients (m(c)) and these were found to be 0.336 and 0.041/h for
      B. thuringiensis and K90, respectively. The results also showed that the values
      of apparent maintenance coefficients were inversely related to the specific
      growth rates. Furthermore, 16S rRNA gene sequencing showed that K90 exhibited
      99.81% sequence similarity to that of B. mojavensis and 92.9% with B.
      thuringiensis. It is evident from the dendrogram that the evolution of B.
      mojavensis (K90) (B. subtilis group), which may have originated after B.
      licheniformis could have been influenced by prolonged hyper-osmotic conditions,
      while B. thuringiensis that evolved before B. oleronius exhibited greater
      sensitivity as implied by the higher maintenance coefficient obtained for the
      hyper-osmotic cultures. As K90 exhibited low maintenance requirements in
      hyperosmotic cultures, close phylogenetic relationship with B. thuringiensis,
      along with the reported property of encapsulation of insecticidal crystal
      proteins (Cry) in Bacillus strains and endophytic nature of B. mojavensis,
      strongly suggest that K90 could be a promising surrogate host for the transgenic
      delivery of "Cry" proteins.

PMID- 15959907
TI  - Oogenesis in the viviparous matrotrophic lizard Mabuya brachypoda.
AB  - Oogenesis in the lizard Mabuya brachypoda is seasonal, with oogenesis initiated
      during May-June and ovulation occurring during July-August. This species ovulates
      an egg that is microlecithal, having very small yolk stores. The preovulatory
      oocyte attains a maximum diameter of 0.9-1.3 mm. Two elongated germinal beds,
      formed by germinal epithelia containing oogonia, early oocytes, and somatic
      cells, are found on the dorsal surface of each ovary. Although microlecithal eggs
      are ovulated in this species, oogenesis is characterized by both previtellogenic
      and vitellogenic stages. During early previtellogenesis, the nucleus of the
      oocyte contains lampbrush chromosomes, whereas the ooplasm stains lightly with a
      perinuclear yolk nucleus. During late previtellogenesis the ooplasm displays
      basophilic staining with fine granular material composed of irregularly
      distributed bundles of thin fibers. A well-defined zona pellucida is also
      observed. The granulosa, initially composed of a single layer of squamous cells
      during early previtellogenesis, becomes multilayered and polymorphic. As with
      other squamate reptiles, the granulosa at this stage is formed by three cell
      types: small, intermediate, and large or pyriform cells. As vitellogenesis
      progresses the oocyte displays abundant vacuoles and small, but scarce, yolk
      platelets at the periphery of the oocyte. The zona pellucida attains its maximum
      thickness during late oogenesis, a period when the granulosa is again reduced to
      a single layer of squamous cells. The vitellogenic process observed in M.
      brachypoda corresponds with the earliest vitellogenic stages seen in other
      viviparous lizard species with larger oocytes. The various species of the genus
      Mabuya provided us with important models to understand a major transition in the
      evolution of viviparity, the development of a microlecithal egg.

PMID- 15959908
TI  - Fine structure of the mineralized teeth of the chiton Acanthopleura echinata
      (Mollusca: Polyplacophora).
AB  - The major lateral teeth of the chiton Acanthopleura echinata are composite
      structures composed of three distinct mineral zones: a posterior layer of
      magnetite; a thin band of lepidocrocite just anterior to this; and apatite
      throughout the core and anterior regions of the cusp. Biomineralization in these
      teeth is a matrix-mediated process, in which the minerals are deposited around
      fibers, with the different biominerals described as occupying architecturally
      discrete compartments. In this study, a range of scanning electron microscopes
      was utilized to undertake a detailed in situ investigation of the fine structure
      of the major lateral teeth. The arrangement of the organic and biomineral
      components of the tooth is similar throughout the three zones, having no discrete
      borders between them, and with crystallites of each mineral phase extending into
      the adjacent mineral zone. Along the posterior surface of the tooth, the organic
      fibers are arranged in a series of fine parallel lines, but just within the
      periphery their appearance takes on a "fish scale"-like pattern, reflective of
      the cross section of a series of units that are overlaid, and offset from each
      other, in adjacent rows. The units are approximately 2 microm wide and 0.6 microm
      thick and comprise biomineral plates separated by organic fibers. Two types of
      subunits make up each "fish scale": one is elongate and curved and forms a
      trough, in which the other, rod-like unit, is nestled. Adjacent rod and trough
      units are aligned into large sheets that define the fracture plane of the tooth.
      The alignment of the plates of rod-trough units is complex and exhibits extreme
      spatial variation within the tooth cusp. Close to the posterior surface the
      plates are essentially horizontal and lie in a lateromedial plane, while
      anteriorly they are almost vertical and lie in the posteroanterior plane. An
      understanding of the fine structure of the mineralized teeth of chitons, and of
      the relationship between the organic and mineral components, provides a new
      insight into biomineralization mechanisms and controls.

PMID- 15959909
TI  - Microtriches of tetraphyllidean metacestodes from Western Mediterranean striped
      dolphins (Stenella coeruleoalba).
AB  - The tegumental structures of two types of tetraphyllidean plerocercoids and two
      types of merocercoids (Phyllobothrium delphini and Monorygma grimaldii) from
      Mediterranean striped dolphins, Stenella coeruleoalba, are described for the
      first time using scanning electron microscopy. The tegument of all of the
      specimens was fully covered with microtriches. Four basic types were found:
      filitriches, blade-like spinitriches of different sizes and shapes, cone-shaped
      spinitriches (with two parallel small projections of equal length at the apex),
      and crowned cylindrical spinitriches (with 6-7 small papillae forming a crown at
      the apex); the two latter types are newly described. The two types of
      plerocercoids had a similar morphology and distribution of microtriches; in
      addition, cilium-like projections appeared interspersed among the microtriches on
      the apical sucker, accessory suckers, and distal bothridial loculus. Merocercoids
      exhibited a greater variety of tegumental structures, especially on the distal
      bothridial loculus. Both merocercoid types had regularly spaced papillae or
      "buttons" on the accessory suckers and the distal bothridial loculus that were
      composed of a central cilium-like projection surrounded by numerous filitriches.
      However, crowned cylindrical spinitriches were specific to P. delphini and cone
      shaped spinitriches were specific to M. grimaldii. Differences in the morphology
      and distribution of scolex microtriches of adult cestodes have been considered
      useful for species identification. A previous molecular study has suggested that
      P. delphini and M. grimaldii are actually different congeneric species. Our study
      has shown that significant differences in the morphology and distribution of
      microtriches occur between these species at the merocercoid stage.

PMID- 15959910
TI  - Hyperfractionated cyclophosphamide with high-doses of arabinosylcytosine and
      methotrexate (HyperCHiDAM Verona 897).
AB  - BACKGROUND: Patients who have aggressive, refractory or recurrent non-Hodgkin
      lymphomas (NHLs) that are refractory to first-line anthracycline-containing
      regimens (ACRs) have a dismal outcome. Achieving complete remission (CR) is
      essential for a favorable outcome. To improve the CR rate in these patients, the
      authors designed a new protocol that contained hyperfractionated cyclophosphamide
      (CTX), high-dose arabinosylcytosine (HiDAC), and high-dose methotrexate (MTX)
      delivered sequentially in the same cycle and followed by the administration of
      granulocyte-colony stimulating factor (G-CSF) (HyperCHiDAM Verona 897). METHODS:
      Between February 1998 and May 2002, 28 consecutive adult patients (median age, 44
      years) with aggressive NHL (B-lineage in 21%, T-lineage in 7%, and Ki-67
      percentage > 50 in 82%) were entered on the protocol after they had failed on
      ACRs (15 patients with refractory disease, 6 patients with stable disease, 5
      patients with recurrent disease, and 2 patients in partial remission). Patients
      characteristics were as follows: Twenty-two patients had Stage III-IV NHL
      (78.6%), 19 patients had B symptoms (67.8%), 22 patients had extranodal disease
      (78.6%), 12 patients had bulky mass (42.8%), 18 patients elevated lactate
      dehydrogenase levels (66%), and 8 patients had high-intermediate/high
      International Prognostic Index scores (64.3%). Patients received
      hyperfractionated CTX (300 mg/m(2)) and HiDAC (2 g/m(2)) every 12 hours on Days 2
      4 and received high-dose MTX (400 mg/m(2) bolus plus 1600 mg/m(2) as a 24-hour
      continuous infusion on Day 1 with folinic rescue), followed by G-CSF.
      Subsequently, 15 patients underwent autologous stem cell transplantation (SCT),
      and 4 patients underwent allogeneic SCT. RESULTS: A CR was achieved by 18 of 28
      patients (64.3%), a partial remission was achieved by 6 patients (21.4%), 4
      patients were nonresponders or had progressive disease (14.3%), and there was 1
      early toxic death (3.5%). Two of 18 patients developed recurrent disease (11.1%).
      The median follow-up for all patients was 35 months (range, from 2 months to > or
      = 74 months). Among the patients who achieved a continuous CR, the median follow
      up was 48 months (range, from > or = 32 months to > or = 73 months). At the time
      of the current report, 13 of 28 patients (46.42%) were event-free. CONCLUSIONS:
      HyperCHiDAM Verona 897 was an effective regimen for patients with aggressive NHL
      who failed on ACRs, and it allowed patients to undergo subsequent SCT.

PMID- 15959911
TI  - The role of anxiety in prostate carcinoma: a structured review of the literature.
AB  - Although the impact of anxiety on patients with some types of cancer is well
      recognized, to the authors knowledge its impact on patients with prostate
      carcinoma has not been studied as thoroughly. The authors conducted a systematic
      review of the medical literature for high-quality articles that quantified
      anxiety levels in men with prostate carcinoma and identified 29 articles. Using
      the clinical timeline of prostate carcinoma to organize the articles, cross
      sectional studies that reflected anxiety prevalence in populations and
      longitudinal studies that reflected changes in anxiety over time were identified.
      Anxiety appeared to fluctuate over the clinical timeline in response to stressors
      and uncertainty (such as at the time of screening and/or biopsy), rising before
      these times and falling afterward. Although anxiety levels in men age > 55 years
      who were at risk for prostate carcinoma were modest (10-15%), multiple studies
      found that these levels were substantially higher in men who presented for
      screening (> 50%), and "seeking peace of mind" was the motivation cited most
      frequently for pursuing screening. Most studies demonstrated a significant
      decrease in anxiety levels after a normal screening or biopsy result, although
      the proportion of men who remained anxious afterward did not fall to baseline
      levels (20-36%). Men who presented for prostate-specific antigen monitoring after
      treatment had elevated anxiety levels at the time of testing (23-33%). Many years
      after therapy for localized disease, anxiety levels were lower after
      prostatectomy (23%) compared with the levels after watchful waiting (31%).

PMID- 15959912
TI  - Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary
      adenoid cystic carcinoma.
AB  - BACKGROUND: Promoter methylation is a common mechanism of inactivation of tumor
      suppressor genes in multiple tumor types. However, little is known about its role
      in the development of adenoid cystic carcinoma of the salivary gland (ACC). In
      the current study, the authors investigated whether promoter methylation is
      common in ACC and whether it may influence ACC development. METHODS: The promoter
      methylation status of the genes p16(INK4a), RASSF1A, DAPK, and MGMT, which are
      important in cell growth regulation, apoptosis, and DNA repair, was determined in
      tissue sections of tumor samples from 60 patients with ACC using methylation
      specific polymerase chain reaction. The association between methylation status
      and patients' clinical and pathologic characteristics were assessed. RESULTS: Of
      the 60 tumors, DNA methylation of the p16(INK4a) promoter was detected in 28
      tumors (47%); the respective values DNA methylation of the RASSF1A, DAPK, and
      MGMT promoters were 25 tumors (42%), 16 tumors (27%), and 4 tumors (7%),
      respectively. Forty-six tumors (77%) had DNA methylation in > or = 1 of the 4
      promoters, 20 tumors (33%) had DNA methylation in > or = 2 promoters, 6 tumors
      (10%) had DNA methylation in > or = 3 promoters, and 1 tumor (2%) had DNA
      methylation in all 4 promoters. RASSF1A promoter methylation was more frequent in
      high-grade tumors than in low-grade tumors (P = 0.009), in advanced-stage tumors
      (P = 0.008), and in tumors with metastasis (P = 0.005). CONCLUSIONS: Promoter
      methylation of p16(INK4a), RASSF1A, and DAPK was common in ACC, and it is
      possible that such methylation may influence the development of ACC. The high
      frequency of RASSF1A promoter methylation in high-grade tumors and in tumors with
      metastasis suggested a role for this gene in the progression of ACC.

PMID- 15959913
TI  - Clinical and genetic findings in an Ashkenazi Jewish population with colorectal
      neoplasms.
AB  - BACKGROUND: The authors evaluated the frequency of the carrier status of three
      ancestral colorectal neoplasm-associated mutations (APC:I1307K, BLM(Ash), and
      MSH2*1906G>C) found in the Jewish population among a case series with documented
      colorectal neoplasms. They further compared family and personal histories plus
      environmental exposures of the carriers and noncarriers of the I1307K mutation
      and examined clinical differences with regard to the colorectal neoplasms and the
      specific molecular genetic changes in these lesions. METHODS: Analyses were
      performed on tissue from stored paraffin-embedded blocks for the three germline
      mutations plus the KRAS mutation and APC loss of heterozygosity (LOH) and APC
      gene sequencing. RESULTS: Fifty-four of the 429 individuals (12.6%) were found to
      carry the APC:I1307K mutation, whereas 4 (0.9%) were found to be heterozygous for
      the BLM(Ash) mutation and 3 (0.7%) were carriers of the MSH21906G>C* mutation.
      Carriers of the I1307K mutation did not appear to differ from noncarriers with
      regard to the number of neoplasms, patient age at detection, or tumor location
      within the colon. There was no significant difference noted between I1307K
      carriers and noncarriers with regard to the percentage of patients with first
      degree relatives with colorectal carcinoma. A significant risk for APC LOH was
      found in lesions from carriers who smoked cigarettes compared with nonsmokers.
      The I1307K mutation was found to be clearly associated with a somatic additional
      adenine insertion in the region of codons 1306-1309, but other mutations in the
      region of codons 1277-1348 were found to be no more prevalent in carriers than in
      noncarriers. CONCLUSIONS: In Jewish individuals previously diagnosed with a
      colorectal neoplasm, MSH2*1906G>C is uncommon but has been associated with
      carcinoma occurring at a young age. The BLM(Ash) mutation is uncommon and appears
      to be of little effect. The I1307K mutation is common among Jews who have had
      colorectal neoplasms, but overall it was found to have little effect clinically
      in the current study group. There may be a gene-environment interaction between
      the I1307K mutation and cigarette use.

PMID- 15959914
TI  - Analysis of extrahepatic bile duct carcinomas according to the New American Joint
      Committee on Cancer staging system focused on tumor classification problems in
      222 patients.
AB  - BACKGROUND: Although the sixth edition of the American Joint Committee on Cancer
      (AJCC) staging system for extrahepatic bile duct carcinoma was updated, the
      system has a problem on T classification due to its ambiguous definition of T1 as
      "tumor confined to bile duct histologically" and T2 as "tumor invading beyond the
      bile duct." METHODS: The authors considered the outermost part of the muscle
      layer or fibrous tissue as within the extrahepatic bile duct and considered the
      area starting from large clusters of adipose tissue as beyond the extrahepatic
      bile duct. After designing a precise definition of the extrahepatic bile duct
      wall, they analyzed the new AJCC staging system in 222 patients with of
      extrahepatic bile duct carcinomas. Then, other clinicopathologic variables for
      prognosis were evaluated using univariate and multivariate analyses. RESULTS: The
      5-year survival rates for patients with tumors that were classified as T1, T2,
      T3, and T4 were 53.1%, 29.7%, 24.9%, and 0%, respectively. There was a
      significant difference in survival between patients with T1 tumors and T2 tumors
      (P < 0.05), but not between patients with T2 tumors and T3 tumors. Significant
      prognostic factors included depth of invasion (P < 0.005), lymph node metastasis
      (P < 0.005), and patient age (P < 0.05). CONCLUSIONS: Based on a proposed
      histologic definition, depth of invasion was practical for evaluating the
      prognosis of patients with middle and upper extrahepatic bile duct carcinomas.
      Therefore, the authors recommended changing the current pT1 and pT2
      classifications to more precise pathologic terminology.

PMID- 15959915
TI  - p63 Expression of clear myoepithelial cells in epithelial-myoepithelial carcinoma
      of the salivary gland: a useful marker for naked myoepithelial cells in cytology.
AB  - BACKGROUND: The typical form of epithelial-myoepithelial carcinoma (EMC) is a
      double-layered ductal structure, but occasionally EMC presents as a predominant
      solid growth of clear myoepithelial cells. In the current study, the authors
      analyzed the distribution and visual patterns of p63-positive clear myoepithelial
      cells in EMC. METHODS: Six cases of EMC were evaluated with Papanicolaou staining
      and with p63 and alpha-smooth muscle actin (SMA) immunostaining. Furthermore, the
      expressions of p63 and SMA were compared. RESULTS: The cytologic features of EMC
      were classified into two types-biphasic and clear cell-dominant type. The
      biphasic type showed myoepithelial cells with moderate or scant cytoplasm or
      naked nuclei, overlapping a cohesive cluster of ductal cells. This biphasic type
      was similar to that in fibroadenoma of the breast. The clear cell-dominant type
      consisted of myoepithelial cells with a large amount of fragile pale cytoplasm or
      naked nuclei. In this type, there were many clusters of myoepithelial cells
      without ductal cells. Nuclear immunoreactivity to p63 was expressed clearly in
      both biphasic and clear cell-dominant types. Cytoplasm immunoreactivity to SMA
      was expressed in many myoepithelial cells in the clear cell-dominant type, but
      only in myoepithelial cells with moderate cytoplasm in the biphasic type.
      CONCLUSIONS: Clear myoepithelial cells in EMC were distributed in various
      patterns. The authors concluded that p63 is an especially useful marker of
      myoepithelial cells with naked nuclei in EMC.

PMID- 15959916
TI  - Hippocampal contributions to neurocognitive mapping in humans: a new model.
AB  - The ability of an organism to develop, maintain, and act upon an abstracted
      internal representation of spatially extensive environments can provide an
      increased chance in ensuring that organism's survival. Here, we propose a
      neurocognitive model of spatial representation describing how several different
      processes interact and segregate the differing types of information used to
      produce a unified cognitive map. This model proposes that view-based egocentric
      and vestibulomotor translational information are functionally and anatomically
      separate, and that these parallel systems result in independent, but interacting,
      models within a neurocognitive map of space. In this context, we selectively
      review relevant portions of the large literature, addressing the establishment
      and operation of such spatial constructs in humans and the brain systems that
      underpin them, with particular reference to the hippocampal formation (HF). We
      present a reinterpretation of the types of knowledge used in the formation of
      this spatial construct, the processes that act upon this information, the nature
      of the final spatial representation, and describe how these universal concepts
      relate to the proposed model of spatial processing. The relevant experimental
      paradigms used to examine the neural basis of spatial representation and the main
      findings from previous research are also briefly presented. Finally, we detail a
      series of testable theoretical, behavioral, and anatomical predictions made by
      the model.

PMID- 15959917
TI  - Corticosterone shifts different forms of synaptic potentiation in opposite
      directions.
AB  - Calcium entering the cell via different routes, e.g.,N-methyl-D-aspartate (NMDA)
      receptors or voltage-dependent calcium channels (VDCCs), plays a pivotal role in
      hippocampal synaptic potentiation. Since corticosteroid hormones have been
      reported to enhance calcium influx through VDCCs, one may predict that these
      hormones facilitate hippocampal synaptic efficacy. Surprisingly, though, stress
      and corticosteroids have so far been found to reduce synaptic potentiation. Here,
      we addressed this apparent paradox and examined synaptic potentiation in the CA1
      area of hippocampal slices from mice with low basal corticosterone levels 1--4 h
      after a brief in vitro administration of corticosterone. Nifedipine and APV were
      used to isolate NMDA receptor-mediated and VDCC-mediated long-term potentiations
      (LTPs), respectively. We report that corticosterone facilitates synaptic
      potentiation that depends on activation of VDCCs while impairing synaptic
      plasticity that is mediated by NMDA receptor activation. The glucocorticoid
      receptor (GR) antagonist RU 38486 blocked both the effects of corticosterone.
      These results indicate that the net effect of corticosteroid hormones on synaptic
      plasticity is determined by the balance between different types of potentiation,
      a balance that may be region specific and depends on the experimental conditions.
      We speculate that these opposite effects on synaptic efficacy are involved in the
      bidirectional modulation of cognitive performance by corticosteroid hormones.

PMID- 15959918
TI  - Dorsal hippocampus NMDA receptors differentially mediate trace and contextual
      fear conditioning.
AB  - The dorsal hippocampus (DH) is critically involved in the acquisition and
      expression of trace and contextual fear conditioning. NMDA/glutamate receptor
      mediated transmission is thought to be one mechanism mediating the plastic
      changes that support long-term memories in the DH. However, their precise
      involvement in acquisition and expression processes has not been defined. To
      examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric
      acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to
      conditioning and/or testing, using a trace fear conditioning procedure. All rats
      were tested for freezing to both tone and context in separate, counterbalanced
      sessions. The three sessions (1 training and 2 test) were separated by
      approximately 24 h. Using this design, it was possible to assess the role for DH
      NMDA receptors in the acquisition versus expression of trace and contextual fear
      conditioning. APV disrupted acquisition, but not expression, of contextual fear
      conditioning. By contrast, APV attenuated both acquisition and expression of
      trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of
      some, but not all, fear memories.

PMID- 15959919
TI  - Catalytic hydrogenation of unsaturated aldehydes on Pt(111): understanding the
      selectivity from first-principles calculations.

PMID- 15959920
TI  - Ruthenium-catalyzed allylic alkylation reactions: carbonate-based catalysts and
      intermediates.

PMID- 15959921
TI  - Guanine and plasmid DNA binding of mono- and trinuclear fac-[Re(CO)3]+ complexes
      with amino acid ligands.
AB  - We have synthesized and fully characterized four new complexes comprising the fac
      [Re(CO)3]+ moiety and the ligands NH3, L-proline (Pro), or N,N-dimethylglycine
      (dmGly). The reaction of [Re(H2O)3(CO)3]+ with the two amino acids gives
      trinuclear complexes of general formula [Re(L)(CO)3]3 (where L = amino acid). We
      have studied the in vitro behavior of these compounds with guanine and DNA in
      order to understand whether the cytotoxicity exhibited by certain rhenium
      complexes based on the fac-[Re(CO)3]+ core is due to the formation of nucleobase
      complexes and inter- or intrastrand links between DNA bases. We have performed
      model studies with guanine and studied the structural effects induced by
      different rhenium(I) tricarbonyl complexes on PhiX174 plasmid DNA by
      electrophoretic methods. Our results show that rhenium complexes with two
      available coordination sites interact with plasmid DNA to form a stable adduct
      that is likely to involve two bases.

PMID- 15959922
TI  - Intraobserver and interobserver reproducibility of three-dimensional gray-scale
      and power Doppler ultrasound examinations of the cervix in pregnant women.
AB  - OBJECTIVES: To determine intraobserver and interobserver reproducibility of three
      dimensional (3D) gray-scale and power Doppler ultrasound examinations of the
      cervix in pregnant women. METHODS: Thirty-two pregnant women underwent
      transvaginal 3D gray-scale and power Doppler ultrasound examination of the cervix
      by two examiners. Each observer acquired two volumes, and they each analyzed
      their volumes twice using the commercially available software Virtual Organ
      Computer-aided AnaLysis (VOCAL). The variables analyzed were cervical volume
      (cm3), vascularization index (VI), flow index (FI) and vascularization flow index
      (VFI). Intraobserver repeatability was expressed as the difference between two
      measurement results (mean difference +/- 2 SD, i.e. limits of agreement) and as
      intraclass correlation coefficient (intra-CC). Interobserver agreement was
      expressed as the difference between the results of the two observers (limits of
      agreement) and as interclass correlation coefficient (inter-CC). The contribution
      of various factors (examiner, acquisition, analysis of acquired volume) to
      intrasubject variance was estimated using different analysis of variance models.
      All statistical analyses were performed using log-transformed data. The results
      presented are those obtained after antilogarithmic transformation, i.e. the
      results are presented as ratios between two results of the same observer, or as
      ratios between the results of Observer 1 and Observer 2. RESULTS: All
      intraobserver and interobserver log-transformed differences were normally
      distributed. There was no systematic bias between the two observers. Both intra-
      and inter-CC values were high (0.93-0.98) for all variables except FI (0.63
      0.88), despite the limits of agreement being wide, especially for VI (widest
      range 0.4-2.4) and VFI (widest range 0.3-2.6). Acquisition explained most of the
      intrasubject variance of the flow indices, the contribution of examiner and
      analysis being unimportant. CONCLUSIONS: Given the wide range between the lower
      and upper limits of agreement, it would probably not be possible to detect
      anything but large differences or changes in cervical volume or cervical flow
      indices using current 3D ultrasound techniques. Because acquisition explained
      most of the intrasubject variance, the average of several repeated acquisitions
      should be used to enhance reproducibility. However, it is not worth doing more
      than one analysis of an acquired volume, because the effect of analysis on
      measurement results is small.

PMID- 15959923
TI  - Metabolic differences between primary and recurrent human brain tumors: a 1H NMR
      spectroscopic investigation.
AB  - High-resolution proton magnetic resonance spectroscopy was performed on tissue
      specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11
      glioblastomas) and 13 patients with meningiomas. For all patients, samples of
      primary tumors and their first recurrences were examined. Increased anaplasia,
      with respect to malignant transformation, resulting in a higher malignancy grade,
      was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features
      of tumor types, as determined on samples of the primary occurrences, were in good
      agreement with previous studies. Compared with the respective primary
      astrocytomas, characteristic features of glioblastomas were significantly
      increased concentrations of alanine (Ala) (p = 0.005), increased metabolite
      ratios of glycine (Gly)/total creatine (tCr) (p = 0.0001) and glutamate
      (Glu)/glutamine (Gln) (p = 0.004). Meningiomas showed increased Ala (p = 0.02)
      and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p = 0.001)
      relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent.
      Metabolic changes of an evolving tumor were observed in recurrent astrocytomas:
      owing to their consecutive assessments, more indicators of malignant degeneration
      were detected in astrocytoma recurrences (e.g. Gly, p = 0.029; tCho, p = 0.034;
      Glu, p = 0.015; tCho/tCr, p = 0.001) in contrast to the comparison of primary
      astrocytomas with primary glioblastomas. The present investigation demonstrated a
      correlation of the tCho-signal with tumor progression. Significantly elevated
      concentrations of Ala (p = 0.037) and Glu (p = 0.003) and metabolite ratio
      tCho/tCr (p = 0.005) were even found in recurrent low-grade astrocytomas with
      unchanged histopathological grading (n = 11). This may be related to an early
      stage of malignant transformation, not yet detectable morphologically, and
      emphasizes the high sensitivity of 1H NMR spectroscopy in elucidating
      characteristics of brain tumor metabolism.

PMID- 15959924
TI  - Investigation of cis/trans ratios of peptide bonds in AVP analogues containing N
      methylphenylalanine enantiomers.
AB  - The solution conformation of vasopressin analogues, modified at positions 2 and 3
      with N-methylphenylalanine or its enantiomer, [D-MePhe2,MePhe3]AVP and [MePhe2,D
      MePhe3]AVP, were studied by 2D NMR spectroscopy in H2O/D2O and theoretical
      calculations (EDMC/ANALYZE). In the case of [MePhe2,D-MePhe3]AVP, the synthesis
      afforded two products, A and B, which had identical molecular ions and similar
      retention times on HPLC. This finding was explained by racemization of Cys1,
      which gave an additional analogue, [D-Cys1,MePhe2,D-MePhe3]AVP (B). The
      possibility is not excluded of racemization of Cys1 in the remaining analogues of
      this series. However, only in the case of [MePhe2,D-MePhe3]AVP was this process
      so distinct that two strong peaks in the HPLC chromatogram were observed. The NMR
      spectra of all the analogues showed several distinct sets of residual proton
      resonances. This suggests that the peptides adopt more than two groups of
      conformations in H2O/D2O. This fact is due to cis/trans isomerization. Two more
      populated isomers arise from the cis/trans isomerization across the 2-3 peptide
      bond in [D-MePhe2,MePhe3]AVP and [MePhe2,D-MePhe3]AVP (A) and across the 1-2
      peptide bond in [D-Cys1,MePhe2,D-MePhe3]AVP (B).

PMID- 15959925
TI  - Abstracts of the 3rd International Conference on Children's Bone Health. 11-14
      May 2005, Sorrento, Italy.

PMID- 15959926
TI  - Abstracts of the XX International Congress on Schizophrenia Research. April 2-6,
      2005. Savannah, Georgia, USA.

PMID- 15959927
TI  - Abstracts of the Annual Meeting of the Obstetric Anaesthetists' Association.
      London, United Kingdom, 12-13 May 2005.

PMID- 15959928
TI  - Letter regarding article by Roguin et al, "Modern pacemaker and implantable
      cardioverter/defibrillator systems can be magnetic resonance imaging safe: in
      vitro and in vivo assessment of safety and function at 1.5 t".

PMID- 15959929
TI  - Letter regarding article by Roguin et al, "Modern pacemaker and implantable
      cardioverter/defibrillator systems can be magnetic resonance imaging safe: in
      vitro and in vivo assessment of safety and function at 1.5 t".

PMID- 15959930
TI  - Neurocognitive impairment does not predict treatment outcome in obsessive
      compulsive disorder.
AB  - There is conflicting evidence pertaining to whether or not neurocognitive task
      performance at baseline predicts treatment response in obsessive-compulsive
      disorder (OCD). In the present study, we administered a set of executive
      neurocognitive tests with a putative sensitivity for treatment outcome to a
      sample of 138 OCD patients. Additionally, subjective neurocognitive dysfunction
      was determined via a questionnaire. All patients participated in a cognitive
      behavioural treatment program (CBT). Results showed that responders (n = 73) did
      not differ from non-responders (n = 65) on any of the parameters except for
      decreased performance on the delayed alternation test (p < .1, effect size: .61).
      A subsidiary analysis revealed that slowing on the Trail-Making Test A and an
      enhanced rate of perserveration errors on the Wisconsin Card Sorting Test
      predicted poor outcome for the treatment of compulsions. It is concluded that
      neurocognitive impairment does not represent a reliable early warning sign for
      non-response to CBT.

PMID- 15959931
TI  - Structural basis of acetylcholinesterase inhibition by triterpenoidal alkaloids.
AB  - Acetylcholinesterase plays a crucial role in the metabolism of neurotransmitter,
      acetylcholine. Inhibition of Torpedo californica acetylcholinesterase by
      triterpenoidal alkaloids buxamine-B (1) and buxamine-C (2) has been studied by
      enzyme kinetics and molecular docking experiments. Buxamine-C (2) has been found
      to be 20-fold potent than buxamine-B (1) (Ki = 5.5 and 110 microM, respectively).
      The ligand docking experiments predicted that the cyclopentanophenanthrene
      skeleton of both inhibitors properly fits into the aromatic gorge of the enzyme.
      The C-3 and C-20 amino groups of both alkaloids mimic the well-known bis
      quaternary ammonium inhibitors such as decamethonium and interact with Trp84 and
      Trp279 residues of the enzyme, respectively. The C-3 amino group in buxamine-C
      (2) appears to be better positioned at the bottom of the aromatic gorge and thus
      seems to be crucial for the inhibitory activity of such inhibitors.

PMID- 15959933
TI  - Putting a new twist on traditional SNF care. Hatsutomi Health Care Hospital.

PMID- 15959932
TI  - Methylmalonic acidemia (MMA).

PMID- 15959934
TI  - Grampa looks thinner: addressing resident malnutrition.

PMID- 15959935
TI  - [Progress in development and application of experimental facilities for life
      sciences on onboard the International Space Station].
AB  - The construction of the International Space Station (ISS) will be completed soon,
      and life sciences studies are important tasks to be carried out onboard.
      Therefore, various related facilities for life science flight experiments are
      being developed aimed at diverse objectives, and some of them were completed and
      passed ground-based simulation experiment or airplane parabolic flight tests, and
      to be arranged for implementation of spaceflight experiments. This article
      reviews comprehensively the recent progress in the development of various types
      of related experimental facilities and the onboard experiments, in the hope that
      it will provide reference for related fields of research.

PMID- 15959936
TI  - [Diagnosis and treatment of conjoined twins].

PMID- 15959937
TI  - LRP and Alzheimer's disease.
AB  - The low-density lipoprotein receptor (LDLR)-related protein, LRP, is a unique
      member of the LDLR family. Frequently referred to as a scavenger receptor, LRP is
      a large transmembrane endocytic receptor that can bind and internalize many
      functionally distinct ligands. Besides its role as a cargo-receptor, LRP has also
      been implicated in many signaling pathways. LRP knockout mice die at early
      embryonic age, which strongly suggests that LRP's functions are essential for
      normal development. Within the CNS, LRP is highly expressed in neuronal cell
      bodies and dendritic processes. In vitro, neurite outgrowth is stimulated by
      apolipoprotein E (apoE)-containing lipoprotein particles via binding to LRP. ApoE
      is the major cholesterol transporter in the brain and human carriers of one or
      two copies of the e4 allele of apoE are at a higher risk of developing
      Alzheimer's disease (AD). LRP also binds the amyloid precursor protein (APP) and
      its proteolytic fragment, the amyloid-beta peptide (Abeta), which are major
      players in the pathogenesis of AD. Finally, LRP has been linked to AD by genetic
      evidence. In this review we discuss the potential mechanisms by which LRP can
      affect APP and Abeta metabolism, and therefore contribute to the pathogenesis of
      AD.

PMID- 15959939
TI  - Rapid gridding reconstruction with a minimal oversampling ratio.
AB  - Reconstruction of magnetic resonance images from data not falling on a Cartesian
      grid is a Fourier inversion problem typically solved using convolution
      interpolation, also known as gridding. Gridding is simple and robust and has
      parameters, the grid oversampling ratio and the kernel width, that can be used to
      trade accuracy for computational memory and time reductions. We have found that
      significant reductions in computation memory and time can be obtained while
      maintaining high accuracy by using a minimal oversampling ratio, from 1.125 to
      1.375, instead of the typically employed grid oversampling ratio of two. When
      using a minimal oversampling ratio, appropriate design of the convolution kernel
      is important for maintaining high accuracy. We derive a simple equation for
      choosing the optimal Kaiser-Bessel convolution kernel for a given oversampling
      ratio and kernel width. As well, we evaluate the effect of presampling the
      kernel, a common technique used to reduce the computation time, and find that
      using linear interpolation between samples adds negligible error with far less
      samples than is necessary with nearest-neighbor interpolation. We also develop a
      new method for choosing the optimal presampled kernel. Using a minimal
      oversampling ratio and presampled kernel, we are able to perform a three
      dimensional (3-D) reconstruction in one-eighth the time and requiring one-third
      the computer memory versus using an oversampling ratio of two and a Kaiser-Bessel
      convolution kernel, while maintaining the same level of accuracy.

PMID- 15959938
TI  - A method to track cortical surface deformations using a laser range scanner.
AB  - This paper reports a novel method to track brain shift using a laser-range
      scanner (LRS) and nonrigid registration techniques. The LRS used in this paper is
      capable of generating textured point-clouds describing the surface
      geometry/intensity pattern of the brain as presented during cranial surgery.
      Using serial LRS acquisitions of the brain's surface and two-dimensional (2-D)
      nonrigid image registration, we developed a method to track surface motion during
      neurosurgical procedures. A series of experiments devised to evaluate the
      performance of the developed shift-tracking protocol are reported. In a
      controlled, quantitative phantom experiment, the results demonstrate that the
      surface shift-tracking protocol is capable of resolving shift to an accuracy of
      approximately 1.6 mm given initial shifts on the order of 15 mm. Furthermore, in
      a preliminary in vivo case using the tracked LRS and an independent optical
      measurement system, the automatic protocol was able to reconstruct 50% of the
      brain shift with an accuracy of 3.7 mm while the manual measurement was able to
      reconstruct 77% with an accuracy of 2.1 mm. The results suggest that a LRS is an
      effective tool for tracking brain surface shift during neurosurgery.

PMID- 15959940
TI  - [Progress in study on mechanisms of rhubarb in treating chronic renal failure].

PMID- 15959942
TI  - Correction: uncited material.

PMID- 15959941
TI  - Overview of epirubicin-based adjuvant therapy in breast cancer.
AB  - Clinical trial data indicate that epirubicin-based adjuvant treatment of breast
      cancer is associated with marked improvement in relapse-free and overall survival
      compared with traditional cyclophosphamide/methotrexate/5-fluorouracil. The
      outcomes are comparable to those achieved with sequential use of
      doxorubicin/cyclophosphamide and paclitaxel. Dose intensification of epirubicin
      is feasible, with tolerable side effects and no increased risk of cardiotoxicity
      beyond that expected. Clinical trial data coupled with pharmacokinetic evidence
      provide a strong foundation and rationale for current and future investigation of
      epirubicin in combination with the taxanes in the adjuvant setting. An ongoing
      German study is evaluating epirubicin/cyclophosphamide in combination with
      trastuzumab as first-line therapy of metastatic breast cancer in patients whose
      tumors overexpress HER2/neu protein. These results, particularly the tolerability
      of this regimen, will form the basis for future adjuvant and neoadjuvant studies
      of epirubicin/trastuzumab-based regimens.

PMID- 15959943
TI  - Statement on influenza vaccination for the 2005-2006 season. An advisory
      committee statement.

PMID- 15959944
TI  - On balanced representation in research.

PMID- 15959945
TI  - Duplicate publication -- some further observations.

PMID- 15959946
TI  - The long and winding road.

PMID- 15959947
TI  - Why big pharma needs to learn the three 'R's.

PMID- 15959948
TI  - Inherent anticipation.

PMID- 15959949
TI  - An audience with... Jan M. Lundberg.

PMID- 15959950
TI  - Future of COX2 inhibitors.

PMID- 15959951
TI  - Abstracts of the 48th Annual Meeting of the Japanese Society of Nephrology.

PMID- 15959952
TI  - Pregabalin.

PMID- 15959953
TI  - Biopharma in Piedmont, Italy.

PMID- 15959954
TI  - Abstracts of the 11th Annual Conference of the British HIV Association (BHIVA)
      with the British Association for Sexual Health and HIV (BASHH). Dublin, Ireland,
      20-23 April 2005.

PMID- 15959956
TI  - Abstracts of the Annual Meeting of the Austrian Society of Hematology and
      Oncology. 28-30 April 2005, Graz, Austria.

PMID- 15959955
TI  - Brassica rapa plants adapted to microgravity with reduced photosystem I and its
      photochemical activity.
AB  - The photosynthetic apparatus contains several protein complexes, many of which
      are regulated by environmental conditions. In this study, the influences of
      microgravity on PSI and PSII in Brassica rapa plants grown aboard the space
      shuttle were examined. We found that Brassica plants grown in space had a normal
      level of growth relative to controls under similar conditions on Earth. Upon
      return to Earth, cotyledons were harvested and thylakoid membranes were isolated.
      Analysis of chlorophyll contents showed that the Chl a/b ratio (3.5) in flight
      cotyledons was much higher than a ratio of 2.42 in the ground controls. The
      flight samples also had a reduction of PSI complexes and a corresponding 30%
      decrease of PSI photochemical activity. Immunoblotting showed that the reaction
      centre polypeptides of PSI were more apparently decreased (e.g. by 24-33% for
      PsaA and PsaB, and 57% for PsaC) than the light-harvesting complexes. In
      comparison, the accumulation of PSII complex was less affected in microgravity,
      thus only a slight reduction in D1, D2 and LHCII was observed in protein blots.
      However, there was a 32% decrease of OEC1 in the flight samples, indicating a
      defective OEC subcomplex. In addition, an average 54% increase of the 54 kDa CF1
      beta isoform was found in the flight samples, suggesting that space-grown plants
      suffered from certain stresses, consistent with implications of the increased Chl
      a/b ratio. Taken together, the results demonstrated that Brassica plants can
      adapt to spaceflight microgravity, but with significant alterations in
      chloroplast structures and photosynthetic complexes, and especially reduction of
      PSI and its activity.

PMID- 15959957
TI  - [Abstracts of the 43rd Meeting of the German Society of Dermatology. Dresden,
      Germany, 20-23 April 2005].

PMID- 15959958
TI  - Psammomatous carcinoid of the rectum.

PMID- 15959959
TI  - [Interventional Cardiology. Proceedings of High Tech 2004 Conference. 28-30
      January 2004, Marseille, France].

PMID- 15959960
TI  - Control of infectious animal diseases by vaccination. Proceedings of a
      conference. Buenos Aires, Argentina, 13-16 April 2005.

PMID- 15959961
TI  - Extension of the expiration date for several body system listings. Final rule.
AB  - We use the Listing of Impairments (the listings) at the third step of the
      sequential evaluation process when we evaluate your claim for benefits based on
      disability under title II and title XVI of the Social Security Act (the Act).
      This final rule extends until July 3, 2006, the date on which listings for four
      body systems will no longer be effective and extends until July 2, 2007, the date
      on which the listings for eight body systems will no longer be effective. Other
      than extending the date during which the listings will be effective, we have made
      no revisions to the listings; they remain the same as they now appear in the Code
      of Federal Regulations. This extension will ensure that we continue to have the
      medical evaluation criteria in the listings to adjudicate disability claims in
      these body systems at step three of the sequential evaluation process.

PMID- 15959962
TI  - Insulin control of glucose metabolism in man: a new kinetic analysis.
AB  - Analyses of the control of glucose metabolism by insulin have been hampered by
      changes in bloog glucose concentration induced by insulin administration with
      resultant activation of hypoglycemic counterregulatory mechanisms. To eliminate
      such mechanisms, we have employed the glucose clamp technique which allows
      maintenance of fasting blood glucose concentration during and after the
      administration of insulin. Analyses of six studies performed in young healthy men
      in the postabsorptive state utilizing the concurrent administration of
      [14C]glucose and 1 mU/kg per min (40 mU/m2 per min) porcine insulin led to the
      development of kinetic models for insulin and for glucose. These models account
      quantitatively for the control of insulin on glucose utilization and on
      endogenous glucose production during nonsteady states. The glucose model, a
      parallel three-compartment model, has a central compartment (mass = 68 +/- 7
      mg/kg; space of distribution = blood water volume) in rapid equilibrium with a
      smaller compartment (50 +/- 17 mg/kg) and in slow equilibrium with a larger
      compartment (96 +/-21 mg/kg). The total plasma equivalent space for the glucose
      system averaged 15.8 liters or 20.3% body weight. Two modes of glucose loss are
      introduced in the model. One is a zero-order loss (insulin and glucose
      independent) from blood to the central nervous system; its magnitude was
      estimated from published data. The other is an insulin-dependent loss, occurring
      from the rapidly equilibrating compartment and, in the basal period, is smaller
      than the insulin-independent loss. Endogenous glucose production averaged 1.74
      mg/kg per min in the basal state and enters the central compartment directly.
      During the glucose clamp experiments plasma insulin levels reached a plateau of
      95 +/-8 microU/ml. Over the entire range of insulin levels studied, glucose
      losses were best correlated with levels of insulin in a slowly equilibrating
      insulin compartment of a three-compartment insulin model. A proportional control
      by this compartment on glucose utilization was adequate to satisfy the observed
      data. Insulin also rapidly decreased the endogenous glucose production to 33% of
      its basal level (0.58 mg/kg per min), this suppression being maintained for at
      least 40 min after exogenous insulin infusion was terminated and after plasma
      insulin concentrations had returned to basal levels. The change in glucose
      utilization per unit change in insulin in the slowly equilibrating insulin
      compartment is proposed as a new measure for insulin sensitivity. This defines
      insulin effects more precisely than previously used measures, such as plasma
      glucose/plasma insulin concentration ratios. Glucose clamp studies and the
      modeling of the coupled kinetics of glucose and insulin offers a new and
      potentially valuable tool to the study of altered states of carbohydrate
      metabolism.

PMID- 15959963
TI  - A history of color. The evolution of theories of lights and color.

PMID- 15959964
TI  - From the editor: The Cardiovascular Institute, the future of CMR.

PMID- 15959965
TI  - Volumetric cine CMR to quantify atrial structure and function in patients with
      atrial dysrhythmias.
AB  - PURPOSE: To implement a cardiac magnetic resonance (CMR)-based protocol to define
      atrial structure and function in individuals with paroxysmal atrial fibrillation
      (PAF), heritable cardiac conduction and myocardial disease with atrial
      dysrhtyhmias (HCCMD), and healthy controls. METHODS: Fifteen controls, 20 PAF,
      and 12 HCCMD subjects underwent CMR examination including: multislice short-axis
      cine, multislice horizontal long-axis cine, and gadolinium-enhanced coronal plane
      magnetic resonance angiography (MRA) for pulmonary vein analysis. We also
      assessed for ventricular myopathy with delayed myocardial enhancement (DME)
      acquisitions. RESULTS: Right and left ventricular measurements did not differ
      among the three groups. Seven heritable atrial dysrhythmia subjects and no
      control or PAF subjects demonstrated midmyocardial fibrosis of the basal
      interventricular septum by DME. Left atrial (LA) volume at the onset of atrial
      systole and minimal LA volume were significantly higher in PAF subjects compared
      to controls (p < 0.05 for both), LA percent emptying was significantly lower in
      PAF subjects (p < 0.01), and RA percent emptying was significantly lower in PAF
      subjects compared to controls (p < 0.01), though these differences were not
      significant when controlling for heart rate, age and gender. There was no
      significant difference in right atrial (RA) volumes among study groups. Atrial
      volumes and function did not differ significantly between heritable atrial
      dysrhtyhmia subjects and controls. PAF subjects had greater frequency of a right
      middle pulmonary vein (RMPV) than controls (6/20 vs. 3/15) that did not reach
      statistical significance. CONCLUSIONS: CMR can quantify atrial structure and
      function in patients with PAF compared to controls. This protocol could not
      detect abnormalities in atrial function in early affected patients with heritable
      cardiomyopathy and atrial premature beats.

PMID- 15959966
TI  - Coronary flow evaluation by TIMI frame count and magnetic resonance flow velocity
      in patients with coronary artery ectasia.
AB  - PURPOSE: Coronary artery ectasia (CAE) is defined as a dilatation of an arterial
      segment to a diameter at least 1.5 times that of the adjacent artery. It is
      characterized by slow flow, predisposing to thrombosis. The TIMI frame count
      (TFC) technique has been successfully used for the assessment of coronary flow
      velocity using coronary angiograms (CA). Our aim was to compare TFC with magnetic
      resonance peak flow velocity (PFV) for the evaluation of the coronary flow in
      patients with CAE. METHODS: Fifteen male patients with CAE, aged 45-60 yrs, and
      15 age-matched male controls were studied by both techniques. Only patients
      without coronary obstructive disease were included. Magnetic resonance coronary
      angiography (MRA) was performed with a 1.5T scanner. The most ectatic part of the
      proximal 1/3 of the vessel involved was examined. Velocity-encoded MR images were
      acquired in a double oblique imaging plane, which was perpendicular to the same
      ectatic segment. The findings were compared with TFC results. RESULTS: Ten
      patients had RCA ectasia and five LAD ectasia. In CAE patients, peak flow
      velocity was 10.7 +/- 1.4 cm/sec in RCA and 11.4 +/- 2.3 cm/sec in LAD. TFC was
      42.9 +/- 7.4 in RCA and 52.0 +/- 20.1 in LAD. In controls, peak flow velocity was
      18.1 +/- 1.9 in RCA and 21.0 +/- 1.7 cm/sec in LAD. TFC was 20.4 +/- 1.59 in RCA
      and 19.8 +/- 1.12 in LAD. Controls had significantly higher peak flow velocity (p
      < 0.001) and lower TFC (p < 0.001) in both RCA and LAD, compared to patients with
      CAE. In patients with CAE, there was a negative correlation between PFV and TFC
      measurements (r = -0.74, p < 0.001). CONCLUSION: Coronary flow in CAE patients
      can be assessed both by TFC and PFV. The noninvasive nature of PFV gives the
      opportunity for serial, easily repeatable, flow evaluation in these patients.

PMID- 15959967
TI  - Differentiation of athlete's heart from pathological forms of cardiac hypertrophy
      by means of geometric indices derived from cardiovascular magnetic resonance.
AB  - PURPOSE: Determination of the underlying etiology of left ventricular hypertrophy
      (LVH) is a common, challenging, and critical clinical problem. The authors aimed
      to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy
      (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in
      athletes, can be distinguished by means of left ventricular volume and geometric
      indices, derived from cardiovascular magnetic resonance imaging. METHODS: A total
      of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical
      Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18),
      competitive athletes (25), patients with HCM (35), aortic stenosis (24), and
      hypertensive heart disease (18). Left ventricular mass index, ejection fraction,
      end-diastolic, end-systolic and stroke volume index, diastolic wall thickness,
      wall thickness ratio and diastolic and systolic wall-to-volume ratios were
      determined. RESULTS: Left ventricular (LV) mass indices were similar for all
      forms of LVH (p > 0.05), which were at least 35% higher than those obtained in
      healthy volunteers (p < 0.05). Multiple logistic regression showed that the
      percentage of correctly predicted diagnoses was 100% for athlete's heart, 80% for
      hypertrophic cardiomyopathy, 54% for aortic stenosis, and 22% for hypertensive
      heart disease. Using a receiver operating curve-determined cut-off value for
      diastolic wall-to-volume ratio of less than 0.15 mm x m2 x ml(-1), athletes'
      hearts could be differentiated from all forms of pathological cardiac hypertrophy
      with 99% specificity. CONCLUSIONS: Athlete's heart can be reliably distinguished
      from all forms of pathological cardiac hypertrophy using CMR-derived LV volume
      and geometric indices, but pathological forms of LVH present with overlapping
      cardiac hypertrophy phenotypes. This capability of CMR should be of high clinical
      value.

PMID- 15959968
TI  - 3 Tesla MR imaging provides improved contrast in first-pass myocardial perfusion
      imaging over a range of gadolinium doses.
AB  - PURPOSE: To compare myocardial enhancement during first-pass myocardial perfusion
      imaging at 3.0 Tesla (T) and 1.5T. MATERIALS AND METHODS: First-pass myocardial
      perfusion imaging was performed on twelve normal subjects at 3T and 1.5T using an
      interleaved notched saturation recovery gradient echo pulse sequence. Subjects
      received either 0.10 mmol/kg for both scans (group 1), 0.075 mmol/kg for both
      scans (group 2), or 0.075 mmol/kg for the 3T scan and 0.10 mmol/kg for the 1.5T
      scan (group 3). RESULTS: Contrast enhancement was significantly greater at 3T
      than at 1.5T for the 12 subjects whether enhancement was normalized to baseline
      signal intensity (2.58 +/- 0.76 vs. 1.52 +/- 0.37, p < 0.0001) or to noise (57.6
      +/- 19.7 vs. 14.7 +/- 7.8, p < 0001). For each of the three groups, contrast
      enhancement was significantly greater at 3T versus 1.5T (p < 0.0001, p < 0.001, p
      < 0.008 when normalized to baseline signal; p < 0.0001 for all groups when
      normalized to noise). CONCLUSION: 3T improves contrast in first-pass myocardial
      perfusion imaging at either 0.10 mmol/kg or 0.075 mmol/kg.

PMID- 15959969
TI  - Determinants of myocardial response in CMR perfusion imaging using Gd-BOPTA
      (Multihance).
AB  - PURPOSE: Different centers and vendors use different sequences and contrast agent
      application schemes for MR myocardial perfusion imaging. The purpose of this
      study was to evaluate the role of different sequences, dosages, and injection
      speeds of contrast media for semiquantitative MR-perfusion assessment. METHODS:
      In a pilot study with 58 consecutive patients three of the most commonly used
      sequences for MR myocardial perfusion imaging (T1-GrE, GrE-EPI or SSFP) were
      compared to each other in terms of peak myocardial enhancement and image quality.
      For the main part of the study dynamic first pass MR perfusion imaging (Philips
      Intera CV, Best, Tthe Netherlands) was performed in 24 patients using the most
      favorable sequence from the pilot study (SSFP) after peripheral i.v.
      administration of Gd-BOPTA during adenosine stress. Two doses (0.05 mmol/kg bw
      and 0.025 mmol/kg bw) and four different injection speeds (8, 4, 3, 2 ml/s) were
      used. Signal intensity time curves were determined in the LV and myocardial
      segments supplied by normal coronary arteries and correlation between LV and
      myocardial upslope as well as peak enhancement were noted. RESULTS: The SSFP
      sequence showed a higher peak enhancement when using 0.05 mmol/kg bw of Gd-BOPTA
      and a superior image quality for both dosage regimen compared with the other
      sequences and was consequently applied for the main study. A significant
      correlation was found between the upslopes in the LV and the myocardium (r square
      = 0.85, p < 0.001). However, LV and myocardial upslopes were largely independent
      of the dosage. Myocardial upslope was significantly slower at an injection rate
      of 2 ml/s compared to 3 and 4 ml/s. Higher Gd-doses led to significantly higher
      enhancement (p < 0.001). CONCLUSION: In healthy myocardial segments, the
      myocardial upslope is mainly determined from the LV upslope. Both myocardial
      enhancement and upslope are largely independent from the injection rate of a
      contrast agent bolus as long as the injection speed is not below 3 ml/s.
      Myocardial enhancement, however, is dose dependent. Thus, a simple correction for
      LV upslope allows to normalize a wide variety of input parameters. Differences of
      myocardial upslope or peak signal intensity after correction should be mainly
      dependent on blood flow.

PMID- 15959970
TI  - Relationship between the extent of non-viable myocardium and regional left
      ventricular function in chronic ischemic heart disease.
AB  - PURPOSE: To define the relationship between left ventricular (LV) regional
      contractile function and the extent of myocardial scar in patients with chronic
      ischemic heart disease and multi-vessel coronary artery disease. METHODS: Twenty
      three patients with chronic ischemic heart disease and 5 healthy volunteers
      underwent magnetic resonance imaging (MRI). In patients, the relative area
      (Percent Scar) and transmural extent (Transmurality) of myocardial infarction
      were computed from short-axis delayed enhancement images. In each image,
      myocardial segments were categorized based on the extent of infarction they
      contained, with 6 categories each for Percent Scar and Transmurality: normal,
      from healthy volunteers; and 0%; 1-25%, 26-50%, 51-75%, and > 76% from patients.
      In patients and volunteers, regional LV function was quantified by absolute
      systolic wall thickening from cine images and midwall circumferential strain
      using tagged images. RESULTS: Compared to normal segments, regional LV function
      in patients was significantly diminished in all scar extent intervals, with wall
      thickening < or = 1 mm and strain > or = -8% for all categories. Systolic wall
      thickening was reduced significantly in all categories above 50% Percent Scar and
      above 25% Transmurality in patients, relative to corresponding 0% categories.
      Circumferential strain was significantly reduced above 25% Percent Scar and above
      25% Transmurality. CONCLUSIONS: In patients with chronic ischemic heart disease
      and multi-vessel coronary artery disease, wall thickening was more sensitive to
      changes in scar Transmurality than to changes in Percent Scar. However,
      circumferential strain was equally sensitive to both indices. In general,
      circumferential strain was more sensitive than wall thickening to increases in
      scar extent.

PMID- 15959971
TI  - A hybrid approach for quantification of aortic valve stenosis using cardiac
      magnetic resonance imaging and echocardiography.
AB  - BACKGROUND: Doppler-derived calculation of aortic valve area (AVA) using the
      continuity equation can be difficult at times, e.g. due to poor acoustic windows,
      heavy calcification of the aortic valve, or significant flow acceleration in the
      left ventricular outflow tract. The aim of this study was to compare AVA as
      assessed by means of transthoracic echocardiography (TTE) with a hybrid approach,
      where the Doppler-derived numerator in the continuity equation was replaced by
      cardiovascular magnetic resonance (CMR) determination of stroke volume. METHODS:
      Twenty consecutive patients admitted for evaluation of aortic stenosis underwent
      transthoracic echocardiography and CMR determination of stroke volume within a
      time period of 3 weeks. Additionally, continuous-wave Doppler spectra of the
      aortic valve were acquired immediately after the CMR examination. RESULTS: There
      was no statistically significant difference for mean AVA between the two methods
      (0.88 +/- 0.23 cm2 by the standard continuity equation versus 0.86 +/- 0.23 cm2
      by the hybrid approach, p = 0.55; r = 0.73, p < 0.01). The mean difference was
      0.02 cm2 and the limits of agreement were -0.32 to 0.36. Only 2 patients were
      classified differently by the two methods. Intraobserver and interobserver
      variability and reproducibility were superior for the hybrid approach.
      CONCLUSION: The hybrid method for determination of AVA is an excellent
      alternative to the standard approach by TTE.

PMID- 15959972
TI  - How much are atrial volumes and ejection fractions assessed by cardiac magnetic
      resonance imaging influenced by the ECG gating method?
AB  - PURPOSE: Most magnetic resonance imaging (MRI) centers currently use prospective
      electrocardiographic (ECG) triggering for image acquisition. Retrospectively
      gated sequences allow the coverage of the entire cardiac cycle. It has been
      recently shown that ventricular volumes and ejection fraction (EF) differ
      according to the gating method used for image acquisition. The authors sought to
      evaluate how much measurements of atrial volumes and EF differ depending on the
      gating method. MATERIALS AND METHODS: Eighteen subjects with no cardiovascular
      disease were investigated by MRI using a 1.5 Tesla scanner. Images were acquired
      with a gradient-echo sequence with steady-state free precession (SSFP) using the
      standard short-axis method for volume and EF measurements. Images were acquired
      with 6 mm thick slices using both prospective triggering and retrospective
      gating. Left and right atrial volumes (end diastolic volume [EDV]; end systolic
      volume [ESV]; stroke volume [SV]) and EF were determined with a commercially
      available software package. RESULTS: ESV was significantly smaller with the
      retrospectively gated SSFP sequence than with the prospectively triggered
      sequence (mean difference: ESV left 3.97 +/- 1.3 ml, p < 0.0001; ESV right 4.34
      +/- 1.8 ml, p < 0.0001). EF and SV were significantly smaller with prospective
      triggering (mean difference: EF left -5.94 +/- 0.9%, p < 0.0001; EF right -5.52
      +/- 1.3 %, p < 0.0001; SV left -3.99 +/- 1.3 ml, p < 0.0001; SV right -4.32 +/-
      1.9 ml, p < 0.0001). EDV remained unchanged (mean difference: EDV left -0.03 +/-
      0.8 ml, p = 0.902; right EDV 0.04 +/- 0.7 ml, p = 0.882). CONCLUSION: The gating
      method has a significant impact on atrial volume and EF measurements. Atrial EF
      is underestimated by using the prospective triggering technique.

PMID- 15959973
TI  - Improved quantification of left ventricular volumes and mass based on endocardial
      and epicardial surface detection from cardiac MR images using level set models.
AB  - PURPOSE: The reproducibility of left ventricular (LV) volume and mass
      measurements based on subjective slice-by-slice tracing of LV borders is affected
      by image quality, and volume estimates are biased by geometric modeling. The
      authors developed a technique for volumetric surface detection (VoSD) and
      quantification of LV volumes and mass without tracing and geometric
      approximations. The authors hypothesized that this technique is accurate and more
      reproducible than the conventional methodology. METHODS: Images were obtained in
      24 patients in 6 to 10 slices from LV base to apex (GE 1.5 T, FIESTA). Volumetric
      data were reconstructed, and endocardial and epicardial surfaces were detected
      using the level set approach. LV volumes were obtained from voxel counts and used
      to compute ejection fraction (EF) and mass. Conventional measurements (MASS
      Analysis) were used as a reference to test the accuracy of VoSD technique (linear
      regression, Bland-Altman). For both techniques, measurements were repeated to
      compute inter- and intra-observer variability. RESULTS: VoSD values resulted in
      high correlation with the reference values (EDV: r = 0.98; ESV: r = 0.99; EF: r =
      0.91; mass: r = 0.98), with no significant biases (8 ml, 5 ml, 0.2% and -9 g) and
      narrow limits of agreement (SD: 13 ml, 10 ml, 6% and 9 g). Inter-observer
      variability of the VoSD technique was lower (range 3 to 5%) than that of the
      reference technique (5 to 11%; p < 0.05). Intra-observer variability was also
      lower (1 to 3% vs. 7 to 10%; p < 0.05). CONCLUSION: VoSD technique allows
      accurate measurements of LV volumes, EF, and mass, which are more reproducible
      than the conventional methodology.

PMID- 15959974
TI  - Measurement of belly composition variability in pigs by in vivo computed
      tomographic scanning.
AB  - The belly region composition of a representative commercial pig sample of 130
      castrates was examined by in vivo spiral computed tomographic (CT) scanning. The
      lean meat percentage, the muscle/fat tissue ratio within the total body and
      separately within the bacon part were estimated by image analysis. The lean meat
      content of the total body was determined by the EU reference method. A
      correlation of r = 0.97 was found between lean meat content of the total body
      determined by CT estimation and the slaughtering results. The pigs were divided
      into seven groups on the basis of their lean meat content. The muscle percentage
      of the bacon part was 26% and 67%, respectively, in the two groups representing
      the two extremes of lean meat percentage (36% and 67%, respectively). The total
      volume of the bacon part was relatively constant (8.6 +/- 1 dm3) in the groups
      representing different lean meat categories. At the same time, the fat tissue
      volume of the bacon part was considerably higher while its muscle tissue volume
      was markedly lower in the group of the lowest than in that of the highest lean
      meat content (6.6 vs. 2.5 dm3 and 2.4 vs. 5.5 dm3, respectively). To describe
      changes in the tissue composition of the bacon part during fattening, 10
      castrates were scanned repeatedly at 70, 90 and 110 kg of liveweight. A linear
      regression model was developed to characterise the continuous decrease observed
      in the muscle/fat ratio within the bacon part due to increasing liveweight.

PMID- 15959975
TI  - Development of a PCR system for the characterisation of Salmonella flagellin
      genes.
AB  - Analysis of flagellin genes was carried out on strains of Salmonella Typhimurium,
      Salmonella Hadar, Salmonella Abortusequi, Salmonella Enteritidis and Salmonella
      Gallinarum serovars, using a PCR system designed in this study. The purpose of
      these studies was to explore the flagellin genes of biphasic and monophasic
      Salmonellae for future targeted genetic interventions. The PCR primers were
      designed for two different structural genes of flagellin (fliC, fljB), for the
      repressor of fliC (fljA), for the operator region of fliC, and for the invertase
      system responsible for phase variation in Salmonella (hin, hixL, hixR). PCR
      analysis revealed that all of the examined genes (fliC, fliC-operator, fljB,
      fljA, hin, hixL, hixR) were present in all S. Typhimurium (n = 10) and S. Hadar
      (n = 10) strains tested. The results obtained on S. Typhimurium and S. Hadar
      strains confirmed their biphasic character at DNA level. However, the S.
      Enteritidis (n = 46) and S. Gallinarum (n = 5) strains lacked the invertase
      system (hin, hixL, hixR) as well as the fljA and fljB genes, while fliC and its
      operator were detectable. Consequently, the S. Enteritidis strains could only
      express fliC gene resulting in phase H1 flagellin. The examined S. Gallinarum
      strains were also demonstrated to have a cryptic flagellin gene (fliC). On the
      other hand, PCR results on S. Abortusequi (n = 2) indicated that both flagellin
      genes (fliC, fljB) and the whole phase variation system were present in both
      strains tested but only the H2 phase gene (fljB) was expressed. The phenotype of
      these strains could be clarified by motility test and/or by classical flagellar
      serology. The findings are also substantiated by the results of serovar-specific
      PCR for S. Typhimurium and S. Enteritidis. In conclusion, the PCR system
      developed in this study proved to be suitable for characterisation of Salmonella
      flagellin genes and confirmed serological results regarding all S. Typhimurium,
      S. Hadar and S. Enteritidis strains. This system could also identify cryptic
      flagellar genes of S. Abortusequi and S. Gallinarum.

PMID- 15959976
TI  - Oesophageal tonsil of the chicken.
AB  - The oesophageal tonsil of the chicken is a novel member of the mucosal-associated
      lymphoid tissue (MALT), which is located around the entrance of the
      proventriculus. It consists of 6 to 8 single units, which are surrounded by a
      thin fibrous capsule. Each one is organised around the bottom of the longitudinal
      folds of the oesophagus, and serves as a 'tonsillar crypt'. Stratified squamous
      epithelium is infiltrated by lymphoid cells, i.e. T cells, plasma cells,
      macrophages, and dendritic cells, but not B cells, to form lymphoepithelium (LE).
      In the LE vimentin-, MHC II- and ATPase-positive cells possibly represent
      Langerhans' cells, but the appearance of 74.3 positive cells in the LE is
      unusual, because the 74.3 monoclonal antibody (mAb) recognises chicken follicular
      dendritic cells in the germinal centre and medulla of the bursal follicles. The
      subepithelial lymphoid tissue is organised into T- and B-dependent regions, which
      are the interfollicular areas and the germinal centres, respectively. Existence
      of high-endothelial venules in the interfollicular region suggests an extensive
      cellular connection between the oesophageal tonsil and the other lymphoid organs.
      In the resting oesophagus the lumen is closed, but during swallowing a bolus the
      crypt opens and the lymphoepithelium can be exposed to undigested food, antigens,
      infectious agents and vaccines. The location of the oesophageal tonsil, cranial
      to the stomach, may provide this organ with a unique role as compared to the
      other parts of the MALT; namely, it may contribute to the replication of
      infectious bursal disease virus (IBDV) and/or the pathogenesis of infectious
      bursal disease.

PMID- 15959977
TI  - Novel strategies to control mycotoxins in feeds: a review.
AB  - Mycotoxin-producing fungi may contaminate agricultural products in the field
      (preharvest spoilage), during storage (postharvest spoilage), or during
      processing. Mycotoxin contamination of foods and feeds poses serious health
      hazard to animals and humans. For lowering mycotoxin contamination of feeds and
      foods, several strategies have been investigated that can be divided into
      biological, chemical and physical methods. This paper gives an overview of
      strategies which are promising with regard to lowering the mycotoxin burden of
      animals and humans.

PMID- 15959978
TI  - Ultrastructural observations on the surface of Thelazia lacrymalis (Nematoda:
      Spirurida, Thelaziidae).
AB  - Scanning electron microscopy (SEM) was used to study the surface ultrastructure
      of female Thelazia lacrymalis obtained from naturally infected cattle. At the
      anterior end, the buccal capsule was cup shaped. The mouth was without lips and
      was surrounded by four cephalic papillae and two amphids. There were two lateral
      cervical papillae. Also, a single small papilla was seen on the ventral side,
      close to the vulvar opening. The vulva was located posterior to the end of the
      oesophagus and the tail carried an anal pore and a pair of phasmids near the tip.
      The cuticle was transversally annulated with fine striations.

PMID- 15959979
TI  - Haemorrhagic nephritis and enteritis of geese: pathomorphological investigations
      and proposed pathogenesis.
AB  - Haemorrhagic nephritis and enteritis of geese as a new disease was first
      described in Hungary in 1969. The authors identified the causative agent of the
      outbreaks occurring in 1969 as a polyomavirus by PCR in 2001. In order to study
      the pathogenesis of the virus, one-day-old goslings were infected with tissue
      homogenate that tested positive for polyomavirus by PCR. Morphological, light and
      transmission electron microscopic (TEM) examinations have revealed that goose
      haemorrhagic polyomavirus replicates in the endothelial cells of the blood
      vessels and capillaries of diseased birds. Infection causes damage and necrosis
      of the endothelial cells. The virus was not observed in the parenchymal cells.
      Oedema and haemorrhages found throughout the body may be due to the dysfunction
      or functional deficiency of endothelial cells damaged by the virus.

PMID- 15959980
TI  - Osteoclast-like giant cell tumour arising from the kidney in a dog.
AB  - In this study, a case of osteoclast-like giant cell tumour arising from the
      kidney is reported in an eight-year-old female Anatolian Shepherd dog.
      Macroscopically, the tumorous mass covered the hilus of the left kidney. It was
      26 x 22 x 12 cm in size and 3700 g in weight. Metastatic tumorous nodules, 0.5
      2.0 cm in diameter, were found on the abdominal side of the diaphragm and in the
      lungs. Microscopically, numerous large osteoclast-like multinucleated giant cells
      and spindle-spheroidal-shaped cells were seen. Osteoblastic differentiation and
      osteoid matrix were noted in a few areas at the periphery of the tumour, near the
      connective tissue septa. The stroma of the tumour tissue was vascular, oedematous
      and loose. By immunoperoxidase staining, tumour cells showed immunoreactivity for
      vimentin but not for keratin and desmin, indicating that the tumour had
      mesenchymal origin. This is the first report in the literature on a malignant
      osteoclast-like giant cell tumour arising from a visceral organ in animals.

PMID- 15959981
TI  - Pharmacokinetics and renal toxicity of three once-a-day doses of amikacin in
      cows.
AB  - Pharmacokinetic variables of amikacin in cows were determined after
      administration of amikacin sulphate either intravenously (IV) or intramuscularly
      (IM) at a dose of 25 mg/kg per day for three days. Amikacin concentrations at
      time zero and maximum serum concentrations were 240.8 microg/mL and 122.53
      microg/mL, respectively. The elimination half-life remained unchanged during the
      three days of administration (T1/2beta = 1.33 +/- 0.029 h for the IV route and
      T1/2beta = 2.75 +/- 0.38 h for the IM route). Apparent volumes of distribution
      suggest limited distribution out of the central compartment (VdAUC = 0.154 +/-
      0.005 L/kg; Vdc = 36.50 +/- 2.35 L; Vdss = 0.092 +/- 0.004 L/kg). Bioavailability
      after IM administration was 95%. Serum profiles of urea, creatinine, albumin,
      electrolytes and pH after 5-day treatment with amikacin at a dose of 25 mg/kg per
      day IM revealed no changes. Assessment of diffusion of amikacin to milk by a
      commercially available screening method to detect antibiotic residues revealed
      that amikacin could not be detected by the fifth milking period after the last
      treatment. These results suggest that it would be rational to use a large single
      daily dose of amikacin for future clinical trials in cows.

PMID- 15959982
TI  - Effect of the in vitro maturation medium on equine oocytes: comparison of
      follicular fluid and oestrous mare serum.
AB  - The present study evaluated the effect of supplementing the medium used to mature
      equine oocytes in vitro with oestrous mare serum (EMS) or horse follicular fluid
      (HFF). To this end, 144 ovaries were obtained from mares aged 16-21 months and
      transported to the laboratory in Dulbecco's phosphate buffered saline (D-PBS) at
      30 degrees C. Oocytes were harvested from the ovaries by slicing, and then
      selected for in vitro maturation (IVM) according to the number of cumulus cell
      layers and the characteristics of the cytoplasm. The selected oocytes were washed
      three times in TCM199 medium plus HEPES (TCM-199H) or in the same medium plus
      glutamine (TCM-199G), then matured in vitro in six study groups established
      according to the in vitro maturation (IVM) treatment to see possible interactions
      between HEPES and glutamine on other supplements: Ten percent EMS was added to
      two of these media (TCM-199H+EMS and TCM-199G+EMS) and 10% HFF was added to the
      media in two other groups (TCM-199H+HFF and TCM-199G+HFF). IVM was performed at
      38.5 degrees C for 40 h in a controlled atmosphere (5% CO2, 95% relative
      humidity). The findings indicate that the presence of EMS or HFF in the TCM-199H
      medium gives rise to the best results in terms of the proportions of oocytes
      reaching maturity (37.7% and 36.8%, respectively). The values obtained with EMS
      and HFF were statistically similar to each other but differed from the other
      treatments. The media containing glutamine led to the highest proportions of
      degenerated oocytes.

PMID- 15959983
TI  - Use of aglepristone and aglepristone + intrauterine antibiotic for the treatment
      of pyometra in bitches.
AB  - In this study, the efficacy of aglepristone and/or intrauterine antibiotic
      administration for the treatment of bitches with cystic endometrial
      hyperplasia/pyometra complex was investigated. Twenty-four bitches (5-12 years
      old) with the diagnosis of pyometra were treated at the University of Kafkas and
      at Istanbul University. The diagnosis of pyometra was established on the basis of
      the results of clinical, ultrasonographic and vaginal examinations, the
      haematological and biochemical findings and the history data. In Group I (n =
      13), aglepristone (Antiprogestin, Alizine, Virbac, France; 0.33 ml/kg, s.c.) was
      administered on days 1, 2, 7, and 14 (day 1: diagnosis). In Group II (n = 11),
      intrauterine antibiotic treatment was performed according to the antibiogram on
      days 1, 2, 4, 6, 8 in addition to aglepristone given as in Group I. Clinical and
      ultrasonographic examinations, haematological results and occurrence of oestrous
      cycles revealed that the ratio of effectively treated bitches was 6/13 and 9/11
      in Groups I and II, respectively.

PMID- 15959984
TI  - A modified surgical technique for repairing third-degree perineal lacerations in
      mares.
AB  - A modified surgical technique has been developed for repairing third-degree
      perineal lacerations in mares. Complications of the currently used methods
      include rectovaginal fistula formation, urine pooling, complete dehiscence of the
      repair, constipation, tenesmus and difficulty of performance in the practice. The
      modified method is simpler and more practical. This method was performed on eight
      Thoroughbred mares with third-degree perineal lacerations after delivery. The
      rectovestibular septum was reconstructed by three lines of sutures in a
      transverse direction in relation to the longitudinal axis of the rectum. In one
      of the eight cases pneumorectum was observed after using the new method. The
      conception rate obtained after using the new surgical technique was 62.5%.
      Pregnant mares delivered normally without any new lacerations at the subsequent
      parturition. It can be concluded that this new surgical technique can be used
      successfully for repairing third-degree perineal lacerations in mares.

PMID- 15959985
TI  - Detection of bovine herpesvirus 4 in CD11b+ leukocytes of experimentally infected
      rabbits.
AB  - The presence and numbers of bovine herpesvirus 4 (BoHV-4) infected CD11b+
      leukocytes were investigated during experimental infections of New Zealand White
      rabbits by Fluorescence Activated Cell Sorter (FACS) analysis. Peripheral blood
      leukocytes (PBL) were collected every second day, and the cells were stained with
      phycoerythrin-labelled CD11b-specific mouse monoclonal antibody and fluorescein
      conjugated bovine herpesvirus 4-specific mouse monoclonal antibody. The numbers
      of double-stained cells from PBLs of the control and inoculated groups were
      measured and compared in FACSTREK analyser. Double-stained cells were detected in
      the virus-inoculated group on postinoculation days (PID) 2-5 and 9-12. The
      results indicated that CD11b+ PBLs were permissive for BoHV-4 infection, and are
      probably the main reservoir of the virus during the latent period. The data did
      not indicate production of infectious viral particles, but virus-specific
      proteins were expressed on the surface of CD11b+ cells. The two waves of double
      stained cells gave similar results to the PCR assays from serum samples, which
      showed the presence of viral DNA in the serum on the same days when virus
      infected CD11b cells were also present. Productive BoHV-4 infection of mast cells
      or undifferentiated leukocytes in the bone marrow and the antiviral immune
      response might be responsible for this periodic appearance of the virus in CD11b+
      PBLs and in the serum. The paper provides evidence that CD11b+ PBLs are the main
      target cell populations in the blood for BoHV-4.

PMID- 15959986
TI  - Clinical perspective of the biological pathway from conception to the maturity of
      performance in the horse: physiology and pathology.

PMID- 15959987
TI  - [PCR as an alternative method for detecting toxigenic strains of Corynebacterium
      diphtheriae].
AB  - PCR standardization was performed in order to detect a fragment and a whole tox
      gene which is presented in all toxigenic strains of Corynebacterium diphtheriae.
      PCR is one of the least time-consuming methods for detection toxigenicity of C.
      diphtheriae strains near EIA (enzyme immunoassay) and ICS (immunochromatographic
      strip) tests.

PMID- 15959988
TI  - [Antibiotic sensitivity of Corynebacterium amycolatum].
AB  - C. amycolatum strains belongs to opportunistic bacteria considered as etiological
      factors of hospital infections. It's usually handled as a human natural flora, so
      antibiotic sensitivity is not checked. There's a few reports relative to
      antibiotic sensitivity of C. amycolatum in the world literature. So, we decided
      to examine antibiotic sensitivity of isolated strains. The 70 of C. amycolatum
      strains isolated from clinical samples from patients hospitalised at Samodzielny
      Publiczny Szpital Kliniczny in Bydgoszcz were analysed. Antimicrobial
      susceptibility testing of the strains was performed by means of a disk diffusion
      method. 28.6% of analysed strains were susceptible to penicillin and 38.6% to
      ampicillin. Susceptibility to another 16 antibiotics was from 40.0% for
      ceftazidime to 64.3% for ceftriaxone. Penicillinase was not produced by analysed
      strains. We stated higher percentage of strains susceptible to combinations of
      penicillin with inhibitors than to penicillin and ampicillin. The most strains
      were susceptible to quinupristin-dealfopristin, linezolid and glycopeptide
      antibiotics but resistance to mupirocin. 35.7% analysed strains were
      multiresistance; there were resistance to beta-lactams (approximately 100%),
      lincosamides (96.0%), macrolides (92.0%) and quinolones (92.0%). Multiresistant
      strains were the most frequently isolated from wound swabs (60.0%) and mainly
      came from patients treated at the departments of general surgery (28.0%) and
      vascular surgery (16.0%).

PMID- 15959989
TI  - [Utilization of released proteins (RPs) of Yersinia enterocolitica for serologic
      diagnosis of yersiniosis. III. Western-blot].
AB  - The usefulness of the immunoblotting using released proteins (Yersinia outer
      proteins-Yop) as the antigen for the serological diagnosis of yersiniosis was
      estimated. The IgA, IgG, and IgM antibody responses of patients with yersiniosis
      and healthy blood donors were studied by western-blot prepared in our laboratory,
      and two commercial assays. The results indicate that antibodies of all three
      classes are most consistently directed against the proteins of YopD, YopM and
      YopE. Good correlations between the three western-blots were obtained for all
      proteins except the protein V-AG. Patients with yersinia-triggered reactive
      arthritis have IgA class antibodies against the YopD more often and for longer
      period than the non-arthritic patients with yersiniosis.

PMID- 15959990
TI  - [Prevalence of Escherichia coli strains in the canteens].
AB  - The prevalence of enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) E. coli
      strains in stool specimens from asymptomatic human carriers working in the
      canteens and also in the kitchen and sanitary facilities was evaluated. The E.
      coli genes coding for the following virulence markers: intimin (eae),
      enterohaemolysin (hlyA), and verotoxins type I and II (stx1 and stx2) were sought
      by multiplex PCR assay. E. coli isolates were obtained from 144 stool specimens,
      295 swabs taken from kitchen hardware and surrounding facilities, and from 33
      meat specimens. Only 66 (8.5%) of total 777 E. coli isolates belonged to O44,
      O18, O25, O127, O55, O114, O125, and O142 serogroups, the prevalent serogroups in
      Poland. None of the strains was classified as serogroup O157. The serogroups O44
      and O18 were present most often among all typeable strains and their incidence
      was 51.5% and 25.8% respectively. Among 363 isolates assayed for the presence of
      the genes encoding virulence markers only 10 isolates (2.8%) carried eae gene.
      None of the isolates possessing eae gene belonged to the serogroups tested. The
      hlyA, stx1 and stx2 genes were absent in all E. coli isolates tested.

PMID- 15959991
TI  - [Characteristics of selected virulence factors of Enterobacter cloacae strains
      isolated from clinical specimens].
AB  - We demonstrated that Enterobacter cloacae possesses a selective haemolytic
      activity on sheep erythrocytes. All the screened strains showed a haemolytic
      activity on sheep erythrocytes when cultures were preincubated with beta
      mercaptoethanol. The investigation circulation of the genes encoding extended
      spectrum beta-lactamases (ESBL) shows that beta-lactamase producers can be
      ascribed to specific patterns of plasmids. We also demonstrated that genetic
      material from E. coli can be transferred and established in selected Enterobacter
      cloacae strains. In a survival tests we demonstrated that similarly to Salmonella
      or Vibrio clinical isolates Enterobacter cloacae doesn't demonstrate acid
      tolerance.

PMID- 15959992
TI  - [Effect of growth conditions on cell surface hydrophobicity of multiresistant
      Pseudomonas aeruginosa strains].
AB  - Bacterial cell surface hydrophobicity (CSH) may promote colonization. The aim of
      this study was evaluation of the influence of growth conditions and sensitivity
      to selected antibiotics on hydrophobic properties of multiresistant P. aeruginosa
      strains by means of salt aggregation test (SAT) and bacterial adhesion to
      hydrocarbons (BATH). 30 multiresistant P. aeruginosa strains were included in
      this study. The variables were: microbiological media type (trypticase-soy agar,
      trypticase-soy agar with 5% sheep blood and trypticase-soy broth), growth
      temperature (22, 30 and 37 degrees C) and growth time (24 and 48 h). Most of the
      investigated strains presented hydrophilic properties in both methods.
      Cultivation in trypticase-soy broth caused statistically relevant decrease of
      CSH. Growth temperature did not influence CSH. 48 hours of incubation caused
      statistically relevant drop of the CSH when compared with 24 h incubation. The
      sensitivity to selected antibiotics did not vary investigated strains, except
      form cefepime sensitive and intermediate sensitive strains.

PMID- 15959993
TI  - [Comparison of bacterial flora in the oral cavity of children and adults].
AB  - The aim of the study was to assess levels of occurrence and number of aerobic
      bacteria hemolysing and non-hemolysing, anaerobic bacteria, streptococci
      hemolysing and non-hemolysing, staphylococci, and bacteria responsible for tooth
      decay (Streptococcus mutans and Lactobacillus spp.) on oral cavity in children
      and adults. The results obtained indicate the difference of the level of
      occurrence of, aerobic bacteria hemolysing and non-hemolysing, anaerobic
      bacteria, streptococci hemolysing and non-hemolysing, staphylococci, and bacteria
      responsible for tooth decay (Streptococcus mutans and Lactobacillus spp.) was not
      statistically significant in either group. The counts and average values of the
      counts for aerobic bacteria non-hemolysing, anaerobic bacteria, streptococci
      hemolysing and non-hemolysing and Streptococcus mutans turned out to be
      statistically significantly larger in adults than in children. However for
      aerobic bacteria hemolysing, staphylococci and Lactobacillus spp. the difference
      of the counts was not statistically significant in either group.

PMID- 15959994
TI  - [Impact of Mycoplasma hominis and Ureaplasma urealyticum on the concentration of
      proinflammatory cytokines in vaginal fluid].
AB  - The main aim of this study was to determine impact of Mycoplasma hominis and
      Ureaplasma urealyticum on the concentrations of selected proinflammatory
      cytokines in vaginal fluid in pregnant women. The samples were obtained from 120
      pregnant women at 22 to 36 weeks gestation. Vaginal fluid were analyzed for the
      concentrations of IL-1 alpha, IL-1 beta, IL-6 and IL-8 using standard enzyme
      linked immunosorbent assay technique (ELISA), and cervical fluid for prevalence
      of Mycoplasma hominis and Ureaplasma urealyticum. Genital mycoplasmas were
      diagnosed in 36 of 120 pregnant women (30%), (in 17 of 36 women (47.2%) both M.
      hominis and U. urealyticum, in 14 women (38.9%) only U. urealyticum, and in 5
      cases (13.8%) only M. hominis were diagnosed). Vaginal levels of IL-8 was
      statistically higher among women with genital mycoplasmas infection, as compared
      to group without these bacteria (p=0.033), while there was no correlation between
      IL-1 alpha, IL-1 beta and IL-6 concentrations and genital mycoplasmas infection.
      Future studies should concentrate on evaluation the impact of other lower genital
      tract bacteria on concentration of IL-8 and other proinflammatory cytokines.

PMID- 15959995
TI  - [Microbiological external quality assurance program (MEQAP)--evaluation of
      results obtained in sanitary epidemiological laboratories in 2002].
AB  - The aim of this study was to evaluate reliability of identification and
      determination of sensitivity to antibiotics and chemotherapeutics of some Gram
      positive cocci strains in 34 sanitary-epidemiological stations. All laboratories
      engaged in this study received 3 strains: S. aureus (S. aureus SC+ CF+, resistant
      to methicillin., or S. aureus SC - CF+, sensitive to methicillin), coagulase
      negative staphylococci (S. epidermidis or S. haemolyticus or S. saprophyticus)
      and Enterococcus sp. (E. faecalis HLAR-positive or E. faecalis HLAR-negative or
      E. faecium or E. gallinarum). All these strains previously were identified in
      Department of Bacteriology of National Institute of Hygiene. Of the 68
      staphylococci strains tested, 66 isolates were correctly identified. Among the 34
      enterococcal strains studied the greatest difficulty in identification was caused
      by E. gallinarum strain--(8 out of 13 strains were incorrectly recognised). The
      determination of the sensitivity of the control strains to antibiotics and
      chemotherapeutic agents, generally was performed correctly in accordance with to
      the NCCLS and national recommendations. Some incorrect results of the
      antibiograms were caused by an erroneous interpretation of the zones of
      inhibition.

PMID- 15959996
TI  - [Comparison of checkerboard and time-kill methods for the analysis of two
      antibiotics combined].
AB  - Activity interaction analysis of two antibiotics by two methods: checkerboard and
      "time-kill" was compared during this study. Combinations of procaine penicillin,
      polymyxin B and bacitracin with neomycin and procaine penicillin with
      dihydrostreptomycin were examined. Checkerboard method is the most widely used
      technique for antimicrobials interactions analyses. The "time-kill" method,
      performed by the broth macrodilution technique, provides a dynamic picture of
      antimicrobial action and interaction over time (based on serial colony counts).
      Differences of "time-kill" method and the checkerboard technique, allow single
      visual examination (after 16 to 24 hours of incubation). Additive and inhibition
      effects were observed in combinations of neomycin with beta-lactam antibiotic
      (procaine penicillin) and peptide antibiotics (bacitracin and polymyxin B) on
      clinical strain S. Enteritidis IL 35 "Time-kill" method also confirmed
      observations mentioned above. In combinations of procaine penicillin with
      dihydrostreptomycin on strains E. coli IL 531 and E. coli IL 256 synergy effects
      on checkerboard technique were noticed. Such observation was not confirmed by the
      "time-kill" method. The methodologies and definitions of synergism are variable
      and not standardized. This situation should be improved, because comparison of
      the results obtained by different methods becomes a very difficult task.

PMID- 15959997
TI  - [Detection of HCV-RNA in liver tissue does not correlate with inflammatory
      process and fibrosis activity in chronic hepatitis C].
AB  - The significance of HCV-RNA presence in the liver tissue in chronic hepatitis C
      activity or prognosis has not yet been clearly explained. Therefore, we have
      examined the relationship between the presence of HCV-RNA in the liver and
      selected parameters of disease activity and liver damage. A group of 48
      chronically HCV infected patients (7-63 years old, mean 39 years) was evaluated.
      In the patients we assessed the activity of transaminases (ALT, AST),
      gammaglutamyltransferase (GGTP), and alkaline phosphatase (ALP). The patients
      underwent routine liver biopsies and the liver tissue was examined
      histopathologically and in order to detect the presence of HCV-RNA, by means of a
      combined procedure joining a new method of HCV-RNA extraction from the liver
      tissue and HCV-RNA detection with RT-PCR automatic Cobas Amplicor Hepatitis C
      ver. 2.0 assay (Roche Diagnostics). At the time of the liver biopsy, 44 of the
      patients were identified as having detectable serum HCV-RNA (as examined by means
      of Cobas Amplicor Hepatitis C ver. 2.0 assay), 3 patients were negative, and 1
      was not tested. The presence of HCV-RNA in the liver tissues was detected in 39
      cases (81.2%). In the parameters examined we have not found any significant
      differences between currently liver HCV-RNA positive and negative patients.
      Presence of the detectable HCV-RNA in the liver bioptats from chronic hepatitis C
      patients does not correlate with disease activity or level of liver damage.

PMID- 15959998
TI  - [Analysis of microorganisms isolated from febrile neutropenic children with
      neoplastic disease].
AB  - The microbiological evaluation of the blood was carried out as a continued
      monitoring of the microorganism culture using the colourmetric system VITAL 200
      (bio-Merieux). There have been analysed 4660 bacteriological research results of
      the peripheral blood, blood from Broviac and from Broviac liquid of the children
      suffering from cancer treated in the years 1997-2000 in the Pediatric, Hematology
      and Oncology Clinique of the State Clinical Hospital in Bydgoszcz. There have
      been gained 1032 positive cultures from KZZ, KZB, PZB. There have been recognized
      259 bacteremia and 22 fungemia by the children with fever in the neutropenia
      period. In the analysed four years in the blood dominated Gram-positive bacteria.
      Among Gram-positive bacteria there were mostly Staphylococcus spp. (42.5%),
      mostly CNS, fewer numerous were Streptococcus spp. (14.5%) and Corynebacterium
      spp. (5.9%). Among Gram-negative bacteria mostly were isolated Acinetobacter spp.
      (25.6%), Pseudomonas spp. (9.7%), E. coli (13.8%), Enterobacter spp. (13.9%),
      Klebsiella spp. (9.2%). There were observed few infections by strains resistant
      to many antibiotics, S. maltophilia, B. cepacia, E. faecium, S. haemolyticus. All
      strains Staphylococcus spp. were sensitive to vancomycin. There have not been
      found Enterococcus spp. resistant to glycopeptides. Most active against Gram
      positive rods were carbapenems and aminoglycosides.

PMID- 15959999
TI  - Rethinking procrastination: positive effects of "active" procrastination behavior
      on attitudes and performance.
AB  - Researchers and practitioners have long regarded procrastination as a self
      handicapping and dysfunctional behavior. In the present study, the authors
      proposed that not all procrastination behaviors either are harmful or lead to
      negative consequences. Specifically, the authors differentiated two types of
      procrastinators: passive procrastinators versus active procrastinators. Passive
      procrastinators are procrastinators in the traditional sense. They are paralyzed
      by their indecision to act and fail to complete tasks on time. In contrast,
      active procrastinators are a "positive" type of procrastinator. They prefer to
      work under pressure, and they make deliberate decisions to procrastinate. The
      present results showed that although active procrastinators procrastinate to the
      same degree as passive procrastinators, they are more similar to
      nonprocrastinators than to passive procrastinators in terms of purposive use of
      time, control of time, self-efficacy belief, coping styles, and outcomes
      including academic performance. The present findings offer a more sophisticated
      understanding of procrastination behavior and indicate a need to reevaluate its
      implications for outcomes of individuals.

PMID- 15960000
TI  - Reactions to 9/11 as a function of terror management and perspective taking.
AB  - The authors used terror management theory to investigate people's reactions to
      the terrorist attacks of 09/11/01. According to the theory, people have a primary
      need to eliminate or reduce existential terror in response to such horrific
      events as 9/11. The authors obtained people's reactions to 9/11, an event in
      which the threat to one's existence was more authentic than those of previous
      events that were imagined. The authors of the present study collected data two
      weeks after 9/11 from young adults on a large university campus in the U.S.
      Midwest. The authors asked participants about their proximal and distal reactions
      to 9/11 and their reasons or motives for those reactions. The results indicated
      that the vast majority of participants' proximal reactions to 9/11 were shock
      and/or disbelief, whereas their distal reactions included performing altruistic
      or prosocial behavior, searching for meaning or value in life, seeking or sharing
      information, spending time in talking to others, and making bigoted remarks about
      Arab Muslims. The main finding was that interpersonal communication is an
      important means of eliminating or reducing existential terror.

PMID- 15960001
TI  - Simple method for predicting American presidential greatness from victory margin
      in popular vote (1824-1996).
AB  - The author tested the simple method (SM) for predicting presidential greatness
      from the winner's victory margin in the popular vote and A. M. Schlesinger Jr.'s
      (1986) cycles of American political history with the expert sample presidential
      rankings of W. J. Ridings Jr. and S. B. McIver (1997). The SM, which involves
      only simple calculations on minimal data available shortly after an election,
      predicts greatness ratings that are above average for winners with high victory
      margins in years of public purpose and for winners with low victory margins in
      years of private interest. Also, the SM predicts ratings that are below average
      for winners with low victory margins in public purpose years and for winners with
      high victory margins in private interest years. Based on the data for 42
      elections from 1824 to 1996, the SM success rate was 81.0% for all elections,
      85.2% for the 27 1st-term elections, 86.2% for elections after 1880, and 94.4%
      for 1st-term elections after 1880. Chi-square analyses showed all percentages
      significant at the .001 level.

PMID- 15960002
TI  - The impact of family status on gender identity and on sex-typing of household
      tasks in Israel.
AB  - The author examined differences in sex-typing of household tasks (adult gender
      roles and children's chores) and differences in gender identity among adult
      Israelis. The author compared 2 groups of participants: single people without
      children (single-family participants; n = 62) and married people with children
      (full-family participants; n = 62). Regarding sex-typing of household tasks and
      direct assessments of masculine and feminine identity, there were no differences
      between single-family participants and full-family participants. However, family
      status affected self-assessments of gender identity that were based on cultural
      definitions of masculine and feminine attributes. Furthermore, correlations
      between direct assessments of gender identity and sex-typing of household tasks
      differed according to family status.

PMID- 15960003
TI  - Antecedents of Taiwanese adolescents' purchase intention toward the merchandise
      of a celebrity: the moderating effect of celebrity adoration.
AB  - The purpose of the present study was to investigate the relative importance of
      adolescents' attitude toward an act (the degree to which the person had a
      favorable or unfavorable evaluation or appraisal of the act's behavior in
      question), perceived norm, and perceived behavioral control in predicting
      Taiwanese adolescents' intention to purchase the merchandise of a celebrity when
      they had different levels of celebrity adoration. The present results showed that
      the relative strengths of attitude toward the act and the perception of
      behavioral control in predicting purchase intention toward the merchandise of a
      celebrity were stronger for adolescents in the celebrity adoration group than for
      adolescents in the celebrity nonadoration group. On the other hand, the relative
      importance of the perceived norm in predicting the attitude toward the act and
      the purchase intention was stronger for adolescents in the celebrity nonadoration
      group than for adolescents in the celebrity adoration group.

PMID- 15960004
TI  - The multidimensional nature of ageism: construct validity and group differences.
AB  - The authors investigated the factor structure and construct validity of the
      Fraboni Scale of Ageism and the age and gender differences in ageism scores.
      Confirmatory factor analyses supported the multidimensional nature of FSA scores
      and generally corroborated the initial factor structure reported by M. Fraboni,
      with some notable exceptions. Essentially, the present findings were aligned with
      theoretical models of ageism that emphasize both cognitive facets and affective
      facets. That is, on the basis of their factor analytic findings, the authors
      redefined Fraboni's original factors of Antilocution, Avoidance, and
      Discrimination as Stereotypes, Separation, and Affective Attitudes, respectively,
      because of the clustering of items within factors. The revised 3-factor structure
      accounted for 36.4% of the variance in FSA scores. FSA factor scores
      significantly related to other scores from other measures of age-related
      attitudes, with higher correlations among factors that were similar in terms of
      their cognitive nature versus their affective nature. Finally, younger
      individuals and men had significantly higher ageism scores on the FSA than older
      individuals and women. The authors discussed the importance of adequately
      assessing ageism, with particular emphasis devoted to the understanding of age
      bias.

PMID- 15960005
TI  - The effects of instrumentality on the relationship between goal orientation and
      leader-member exchange.

PMID- 15960006
TI  - How do I get started building a neonatal nursing career?

PMID- 15960008
TI  - A review of harlequin ichthyosis.
AB  - Harlequin ichthyosis is an extremely rare and historically lethal congenital
      disorder of the skin caused by abnormal keratinization. This article reviews the
      embryology and currently understood pathophysiology of the disease, as well as
      current methods used to diagnose and treat these infants. There are serious
      implications for the family to consider: the high risk that their newborn will
      die soon, as well as future family planning issues.

PMID- 15960007
TI  - The early feeding skills assessment for preterm infants.
AB  - Preterm infants develop the skills necessary to begin oral feeding as their
      health stabilizes and as they reach a postconceptional age that supports
      coordination of breathing and swallowing with oral-motor functioning. The time
      from initiation of oral feeding to full oral feedings (with adequate intake for
      growth and maintenance of physiologic stability) can vary from days to months for
      the preterm infant. The approach to feeding the infant during this transition
      period must be developmentally supportive and tailored to meet the needs of the
      individual. To accomplish this, caregivers--notably nurses and parents--need to
      communicate about the specific skills that the infant has gained, about skills
      that are emerging, and about skills that the infant has not yet developed. The
      Early Feeding Skills (EFS) Assessment is a checklist for assessing infant
      readiness for and tolerance of feeding and for profiling the infant's
      developmental stage regarding specific feeding skills: the abilities to remain
      engaged in feeding, organize oral-motor functioning, coordinate swallowing with
      breathing, and maintain physiologic stability. This article introduces the EFS.

PMID- 15960009
TI  - Parents and professionals in the NICU: communication within the context of
      ethical decision making--an integrative review.
AB  - Communication between parents and professionals in the NICU is a necessary part
      of collaborative decision making in the provision of family-centered care.
      Decisions with ethical components, those regarding treatment plans or neonatal
      research enrollment, need to be made conjointly with parents and health care
      professionals. This article reviews the present state of knowledge of how
      parents' input can be facilitated in regard to decisions made about their
      children. Research studies involving decisions made with ethical components in
      the NICU since the advent of the Baby Doe regulations reveal parents' frustration
      with communication practices, their need for control of information, and the
      trust in their children's health care providers that is required to best
      facilitate their input into ethical decisions made about their children.

PMID- 15960010
TI  - Identifying, understanding, and working with grieving parents in the NICU, Part
      I: Identifying and understanding loss and the grief response.
AB  - The admission of an infant to an NICU is an unexpected event for the parents and
      one often not predicted by health care professionals. This highly stressiful and
      overwhelming hospitalization is likely to be one of the greatest life challenges
      that parents of newborns face. Parents need support from NICU professionals,
      among others, to cope with the losses that occur in the hospital setting. This
      article provides NICU professionals with general information about loss and the
      subsequent grief response, focusing on losses from sources other than death.
      Common emotional and physical responses are provided so these can be recognized
      in affected parents. By increasing their awareness of the topics of loss and
      grief, health care professionals can help ensure that grieving parents get the
      support needed to assimilate their loss into a life forever changed.

PMID- 15960011
TI  - Intraventricular hemorrhage in the premature neonate.
AB  - Intraventricular hemorrhage in the premature neonate has been and continues to be
      a cause of morbidity and mortality in NICUs around the globe. Much information is
      available concerning the etiology and preventative and treatment strategies to
      reduce the incidence of IVH in this patient population. As neonatal caregivers
      are struggling to care for and protect infants who are surviving despite extreme
      prematurity, this survival is complicated by the infant's cerebral vasculature,
      which is very susceptible to hemorrhage; by respiratory problems that require the
      use of lifesaving, but potentially harmful, ventilation interventions; and by the
      infant's compromised ability to self-regulate vascular responses to stress. The
      preventative treatments being explored and proposed may come with debilitating
      and potentially lethal sequelae. Research continues, however. New recommendations
      are being proffered, and perhaps, in the near future, the incidence of IVH and
      its associated morbidity and mortality will decline dramatically.

PMID- 15960012
TI  - The integration of research and practice: the importance of examining the
      evidence.

PMID- 15960013
TI  - A "moment" in the NICU.

PMID- 15960014
TI  - Using a bundle approach to improve ventilator care processes and reduce
      ventilator-associated pneumonia.
AB  - BACKGROUND: A "bundle" of ventilator care processes (peptic ulcer disease
      prophylaxis, deep vein thrombosis prophylaxis, elevation of the head of the bed,
      and a sedation vacation), which may also reduce ventilator-associated pneumonia
      (VAP) rates, can serve as a focus for improvement strategies in intensive care
      units (ICUs). Between July 2002 and January 2004, teams of critical care
      clinicians from 61 health care organizations participated in a collaborative on
      improving care in the ICU. METHODS: ICU team members posted data monthly on a Web
      based extranet and submitted narrative descriptions describing the changes tested
      and the strategies implemented. RESULTS: For the 35 units that consistently
      collected data on ventilator bundle element adherence and VAP rates, an average
      44.5% reduction of VAP was observed. DISCUSSION: The goal-oriented nature of the
      bundle appears to demand development of the teamwork necessary to improve
      reliability. The observations seem sufficiently robust to support implementing
      the ventilator bundles to provide a focus for additional change in ICUs.

PMID- 15960015
TI  - Reducing waste and errors: piloting lean principles at Intermountain Healthcare.
AB  - BACKGROUND: The Toyota Production System (TPS), based on industrial engineering
      principles and operational innovations, is used to achieve waste reduction and
      efficiency while increasing product quality. Several key tools and principles,
      adapted to health care, have proved effective in improving hospital operations.
      TOOLS: Value Stream Maps (VSMs), which represent the key people, material, and
      information flows required to deliver a product or service, distinguish between
      value-adding and non-value-adding steps. The one-page Problem-Solving A3 Report
      guides staff through a rigorous and systematic problem-solving process. PILOT
      PROJECT at INTERMOUNTAIN HEALTHCARE: In a pilot project, participants made many
      improvements, ranging from simple changes implemented immediately (for example,
      heart monitor paper not available when a patient presented with a dysrythmia) to
      larger projects involving patient or information flow issues across multiple
      departments. Most of the improvements required little or no investment and
      reduced significant amounts of wasted time for front-line workers. In one unit,
      turnaround time for pathologist reports from an anatomical pathology lab was
      reduced from five to two days. CONCLUSIONS: TPS principles and tools are
      applicable to an endless variety of processes and work settings in health care
      and can be used to address critical challenges such as medical errors, escalating
      costs, and staffing shortages.

PMID- 15960016
TI  - Taking a patient safety approach to an integration of two hospitals.
AB  - BACKGROUND: Consolidation of inpatient care between two acute care medical
      centers brings many challenges, including an increased risk of an untoward event
      during patient transfer and impaired hospital performance during the
      postintegration period. When the Jesse Brown Department of Veterans Affairs (VA)
      Medical Center in Chicago integrated two acute medical-surgical inpatient
      facilities, the challenges intrinsic to simultaneously integrating acute medical
      surgical programs and academic training programs necessitated a novel approach.
      STRATEGIES USED: Several patient safety-related tools were used for the safe
      transfer of patients and for sustaining hospital performance after integration.
      These tools included Failure Mode and Effects Analysis (FMEA) of the move
      process, process action teams to bridge the differences in standard nursing unit
      operation, and an integration score card to monitor and evaluate the impact of
      the integration on organization performance. RESULTS: Patient care was not
      disrupted except for a transient reduction in elective surgical procedures during
      the week before the move. Postintegration data indicated reduced operating room
      cancellations, sustained inpatient capacity and access, and comparable findings
      in patient falls and methicillin-resistant Staphylococcus aureus and vancomycin
      resistant enterococci infections. CONCLUSION: The impact of several patient
      safety tools and interventions was reflected in the fact that performance
      remained constant or improved for the predefined measures of access and quality.

PMID- 15960017
TI  - An osteoporosis and fracture intervention program increases the diagnosis and
      treatment for osteoporosis for patients with minimal trauma fractures.
AB  - BACKGROUND: As fewer than 25% of patients with an osteoporotic minimal trauma
      fracture (MTF) are evaluated and treated for osteoporosis, an osteoporosis and
      fracture intervention program (OFIP) was developed. METHODS: Patients
      hospitalized with MTF were educated about and treated for osteoporosis and were
      evaluated by the osteoporosis team at 6 and 12 months after discharge. Patients
      seen in the emergency department were given information about osteoporosis and
      encouraged to seek medical care at the osteoporosis office. RESULTS: While 165
      patients hospitalized with an MTF participated in the OFIP, 38 patients received
      routine osteoporosis education. At the 6-month follow-up, in the OFIP group, 68%
      of patients with hip fracture and 54% of patients with non-hip fracture were
      taking antiresorptive medications. There was no change in treatment rate among
      patients receiving conventional care. CONCLUSIONS: The rates of diagnosis of
      osteoporosis and treatment implementation following an MTF increased when the
      intervention occurred at the time of hospitalization.

PMID- 15960018
TI  - One-year follow-up after a collaborative breakthrough series on reducing falls
      and fall-related injuries.
AB  - BACKGROUND: Multisite facilitated quality improvement (QI) projects, called
      collaborative Breakthrough Series (BTS), have been shown to improve care, but it
      is also important to evaluate the lasting effects and spread of changes of BTSs.
      A project focused on fall and injury-related prevention started in Spring 2001;
      after the project's end, support was provided through e-mail and periodic
      conference calls. METHODS: One year after project completion, team contacts were
      interviewed to determine if they had maintained gains or made further
      improvements. RESULTS: For the 34 (of 37 teams) interviewed, 82.4% reported they
      had stayed together as a team; 97.1%, that they continued to collect data; 93.9%,
      that they had maintained gains; 82.4%, that they had spread changes to new
      locations; and 85.3%, that they had begun to work on new topics. High team
      performance at one year correlated with first-meeting team characteristics
      Leadership Support (r = .456, p = .019) and Prior Experience with Quality
      Improvement and Teamwork (r = .393, p = .047) and with follow-up team
      characteristics Leadership Support (r = .614, p < .001), Teamwork Skills (r =
      .377, p = .033), and Skills Gained from the Project (r = .410, p = .020).
      CONCLUSIONS: Leadership support, experience with quality improvement and
      teamwork, teamwork skills, and skills gained from the project were correlated
      with teams' abilities to achieve and maintain success.

PMID- 15960019
TI  - Promoting influenza and pneumococcal immunization in older adults.
AB  - BACKGROUND: Reducing the risk of influenza and pneumococcal disease in older
      adults is a long-standing goal of Medicare's Quality Improvement Organization
      (QIO) program and parallels the Joint Commission's National Patient Safety Goal
      10. ADDRESSING THE GOAL: Since 1999 the West Virginia Medical Institute has
      worked with a statewide partnership of health organizations on a program to
      improve influenza and pneumonia vaccination rates in hospitalized Medicare
      beneficiaries. Methods included education, audit and feedback, toolkits, and
      training meetings. RESULTS: During the first three years (1999-2001) of the
      effort, the rate of assessment for pneumococcal immunization at discharge
      increased from < 10% to 74.1% statewide and for influenza immunization from near
      zero to 63.4% statewide. Since 2002 pneumococcal immunization administration has
      increased from 16.1% to 41.1%, with similar improvement in influenza measures.
      LESSONS LEARNED/NEXT STEPS: Hospitals--and, by extension, long term care
      facilities--can make dramatic improvements in quality performance in a relatively
      short time when key staff receive feedback about the need to improve and the
      tools to assist in improving.

PMID- 15960020
TI  - Reducing at-risk behaviors.
AB  - All to often, one of the most deeply seated roots of system problems--an
      organizational culture with a high tolerance of at-risk behaviors--is overlooked.

PMID- 15960022
TI  - Educating future healthcare managers: meeting contemporary challenges.
AB  - University programs must work to keep curricula sufficiently dynamic to assure
      knowledge content remains relevant, appropriate skills are developed, and
      standards of academic rigor are maintained. This paper describes a curriculum
      analysis for a healthcare management program conducted in 1997 and the subsequent
      steps taken to enhance the program through more formalized links with healthcare
      organizations. In describing the curriculum analysis, a special emphasis is
      placed on data compiled in 1996 from a small exploratory study conducted to
      identify which content areas, skills, and experiences healthcare employers in the
      state of Maryland noted to be most important for a new hire from an undergraduate
      program. The program was recently granted Full Certified Undergraduate membership
      in the Association of University Programs in Health Administration (AUPHA). The
      paper concludes with a discussion of the changes to the curriculum implemented
      since 1997 and the process initiated to continually assess the quality of the
      revised program.

PMID- 15960023
TI  - Healthcare ethics: a pedagogical goldmine.
AB  - The author explores how a well designed and delivered course in healthcare ethics
      can meet multiple curricular goals in a health administration program. The basic
      philosophy, content, and methods of instruction are presented along with
      discussion of the effectiveness of using ethics as a platform for development of
      critical analysis and decision-making skills. The author illustrates how the
      course meets specific curricular criteria for program accreditation by the
      Commission on Accreditation of Healthcare Management Education (CAHME). Finally,
      a number of specific challenges related to the design and delivery of an
      effective course in healthcare ethics are addressed including course design,
      materials of instruction, and faculty.

PMID- 15960024
TI  - The Latino Healthcare Professionals Project: responding to the diverse needs of
      the 21st century.
AB  - The Latino Healthcare Professionals Project (LHPP) is a privately-funded
      initiative to provide healthcare management training to first-generation educated
      Latino bilingual and bicultural upper division university students planning
      careers in healthcare. This unique curriculum, scholarship, and mentorship
      program is based in the Health Care Administration (HCA) Program at California
      State University Long Beach (CSULB). Initially funded by The Sisters of St.
      Joseph Healthcare Foundation, LHPP has been sponsored by several organizations,
      including Kaiser Permanente and the Health Care Foundation for Orange County,
      with a shared commitment to increase the diversity of trained Latino managers in
      the healthcare field. Since its inception in 1995,168 students have participated
      in LHPP, with demonstrated success in improved student performance, retention,
      participation in the health professional work force, and continuing educational
      achievements. This article discusses the need for Latino healthcare
      professionals, current issues facing the Latino population with regard to higher
      education and family involvement, and barriers affecting Latino students' ability
      to complete a four-year baccalaureate degree. Information on the projectincludes
      a description of the LHPP mission and goals, curriculum and core components, as
      well as the project's structure, process, and outcomes.

PMID- 15960025
TI  - Preparing for diversity management strategies: teaching tactics for an
      undergraduate healthcare management program.
AB  - This paper reports the processes used by faculty in the Bachelor of Science in
      Health Sciences (BSHS) Program at the University of Alabama at Birmingham to
      increase diversity knowledge for the faculty and to incorporate diversity
      management issues and skills development into the program curriculum using a
      structured plan.

PMID- 15960026
TI  - Teaching healthcare marketing via community research: the LifeFlight project.
AB  - Undergraduate students in Healthcare Administration programs may benefit from
      cooperative learning strategies such as participation in community research.
      Collaborating with local healthcare facilities on class projects also encourages
      more active engagement between the academic and practice communities. This
      purpose of this paper is to briefly describe one collaborative venture
      undertakenby undergraduates in a Marketing for Healthcare Organizations class and
      a LifeFlight program at a local hospital. The students carried out a survey of
      members in the program, conducted a SWOT analysis, and made relevant
      recommendations. Student evaluations of this experience were positive, as was the
      hospital's assessment.

PMID- 15960027
TI  - Integrating long-term care education into undergraduate health administration
      education programs.

PMID- 15960028
TI  - Articulation of undergraduate and graduate education in health administration:
      barriers and strategies for the future.
AB  - The initiation of the hospital administration degree at the master's level and
      not the baccalaureate level was an intentional decision. Unfortunately, during
      this formative half-decade, the baccalaureate programs developed in a vacuum,
      isolated from one another and from the long-established graduate programs. While
      there is not a clear professional consensus that the lack of undergraduate degree
      articulation with graduate education is a problem, the authors believe this to be
      the case and believe that many faculty agree. This paper will address the history
      of health administration education, current academic pathways to careers in
      health administration, and detailed barriers and strategies to academic degree
      articulation. The paper concludes that discussion of health administration degree
      articulation has received modest attention and discussion for more than twenty
      years, and neither formal relationships nor certification/accreditation has
      addressed the issue. The authors believe that creation of articulated degrees is
      desirable and call for AUPHA and CAHME to develop a task force to address
      barriers and strategies for articulation. Concurrently, while national policy
      would facilitate more rapid change, we recommend that individual undergraduate
      and graduate degree programs explore individual relationships as a means to
      achieve models for the profession as an alternative to the status quo.

PMID- 15960029
TI  - Apologizing: trying to get it right.
AB  - It is hardly possible to go through a day without "stepping on someone's toes."
      By practicing the steps described in this article, you can strengthen your
      ability to engage in an apology process that is powerful and healing. Being
      truthful and courageous about your own part of a situation opens the door for
      others around you to do likewise. People will experience you as a person who has
      integrity. Receiving an apology from another person allows you to complete the
      process by forgiving.

PMID- 15960030
TI  - Enhancing communication with older adults: overcoming elderspeak.
AB  - Because communication behaviors are difficult to change, practicing speech
      without elderspeak is helpful in preparing for actual clinical situations. The
      Communication Enhancement Model describes potential benefits of eliminating
      elderspeak in speech to older adults. Minimizing the use of elderspeak is
      hypothesized to reduce stereotype-based messages that older adults are
      incompetent and dependent. An improved communication environment promotes the
      cognitive and functional abilities of older adults. Achieving optimal
      communication environments may contribute to higher levels of well-being for
      older adults and to increased quality of life. Young adult care providers also
      may benefit from increased job satisfaction if they relate closely with care
      recipients.

PMID- 15960031
TI  - Smoking reduction & cessation: a hospital based survey of outpatients' attitudes.
AB  - 1. Most people with mental illnesses have made at least one attempt to quit
      smoking on their own. 2. Psychiatric diagnosis and degree of nicotine dependence
      do not appear to be predictive of ability to quit. 3. People with mental
      illnesses are aware of nicotine replacement therapy (NRT), but do not combine it
      with a behavioral program, possibly contributing to the higher rates of
      recidivism in this population. 4. The lack of participation of mental health care
      providers in promoting smoking cessation is a complex issue.

PMID- 15960032
TI  - Cognitive therapy: a training model for advanced practice nurses.
AB  - 1. Mental health needs exist in medically underserved areas and can be addressed
      in nurse-managed, community-based health centers. 2. Cognitive therapy techniques
      can be used in community-based health centers to intervene and alleviate
      patients' distress and improve their adherence to treatment. 3. A training
      program in cognitive therapy can help advanced practice nurses and other health
      care providers implement the techniques needed to address many behavioral and
      mental health problems.

PMID- 15960033
TI  - Intimacy boundaries: between mental health nurses & psychiatric patients.
AB  - This was the first research study in Canada to explore intimacy boundary
      violations and sexual misconduct between nurses (both RNs and registered
      psychiatric nurses) and patients. Using a researcher-generated survey, a total of
      923 mental health nurses commented on their sexual attraction to patients, and
      dating and sexual intercourse patterns with patients. The findings indicated that
      very few nurses had dated or engaged in sexual intercourse with discharged
      patients, and the few nurses who had done so tended to be younger men prepared at
      the registered psychiatric nursing diploma level. A small number of nurses
      believed it was permissible to have a sexual relationship with a patient while
      the patient was hospitalized, but none reported having a current relationship.
      Given the severity of this intimacy boundary violation, nurses need to be
      educated regarding the serious and dangerous psychiatric effects that can result
      for patients from engaging in a sexual relationship with nurses. The Code of
      Ethics of the Canadian Nurses Association and nurses' obligation to follow it
      needs to be reinforced. Nurses engaging in intimacy boundary violations are
      vulnerable to patient-initiated lawsuits.

PMID- 15960034
TI  - Creative solutions: Innovative use of the arts in mental health settings.
AB  - A recent study of occupational stress on the unit (Clare, 2004) highlighted that
      staff valued the importance of the socialization process in reducing their stress
      levels. This process incorporates the need for peer support and acceptance, and
      an understanding of what is expected of them (e.g., roles and responsibilities),
      supported by a culture of learning, problem solving, and working together. This
      process is similar to the approach taken by the arts project in nurturing ideas
      and initiatives in a safe, respectful way. It is apparent that the arts project
      has been more than just a creative activity; it has had wider implications for
      both staff and service users in reducing stress. It has: * Enabled staff
      retention. In fact, there is a waiting list of nurses wishing to work on the
      unit. * Reduced incidents of damage to property. * Reduced use of p.r.n.
      medication. * Enhanced the good reputation of the service, which is often
      commented on by visitors to the unit. The arts project promotes well-being and
      lifelong learning for the ward community through meaningful engagement in
      creative activity.

PMID- 15960035
TI  - RNs - we've come a long way.

PMID- 15960036
TI  - Orthopaedic surgery 2005: new concepts--new controversies.

PMID- 15960037
TI  - Resident work hours: the great change.

PMID- 15960038
TI  - Effective and efficient charitable giving.

PMID- 15960039
TI  - Technology in medical practice.

PMID- 15960040
TI  - Seatbelt/helmet enforcement needed.

PMID- 15960042
TI  - Radiologists seek monopoly.

PMID- 15960043
TI  - Radiologists sole interpreters?

PMID- 15960044
TI  - Minimally invasive total hip arthroplasty: experience at Saint Louis University.
AB  - Minimally invasive total hip arthroplasty is used to describe both newer surgical
      approaches or simply smaller than standard incisions for the implantation of
      artificial hip joints. These new techniques have created interest,
      misunderstanding and controversy for patients and physicians. However, early
      indications are that minimally invasive hip surgery is an improvement compared to
      traditional surgery. Lack of purpose-specific equipment and the need to learn new
      operative skills are factors that may slow the acceptance of these techniques.

PMID- 15960045
TI  - Hip pain in the young adult.
AB  - Hip pain in the adult between 20 and 40 years of age may present as a diagnostic
      and treatment dilemma. Recently, adult developmental dysplasia of the hip and
      femoroacetabular impingement have been identified as important pathologic causes.
      These disorders often present with subtle initial findings. However, early
      diagnosis and treatment are critical to avert or delay the need for
      reconstructive surgery.

PMID- 15960046
TI  - Innovations in the treatment of low back pain.
AB  - Nonoperative care of the low back pain patient has changed little over the past
      15 years. However, injections to localize pain have become increasingly more
      sophisticated for both diagnosis and treatment. Advances in surgical treatment
      have been dramatic. Minimally invasive techniques shorten postoperative recovery
      time by decreasing local tissue trauma. Disc replacement is a new option for
      treating the degenerative disc; offering the prospects of rapid postoperative
      recovery and maintenance of range of motion.

PMID- 15960047
TI  - New techniques in hip fracture management.
AB  - Hip fractures in the elderly are usually caused by low-energy trauma, such as a
      fall from standing. These fractures involve the femoral neck or the
      intertrochanteric region of the proximal femur. Timely surgical intervention
      provides superior outcomes. Newer fracture fixation implants and improved design
      of prosthetic replacements have contributed to progress in the management of
      these fractures. However, post-fracture osteoporosis evaluation by the primary
      care physician is equally important.

PMID- 15960048
TI  - Current concepts for treatment of the painful flatfoot in the elderly.
AB  - Flatfoot deformities are predominantly asymptomatic variants of normal, which do
      not adversely affect function. However, the acquired flatfoot deformity secondary
      to attrition of the posterior tibial tendon is a progressively painful condition,
      ultimately affecting the hindfoot, midfoot, and forefoot. It is most common
      during the sixth and seventh decades of life. Chronic micro-trauma to the tendon
      causes eventual rupture and the resulting deformity. Prior to tendon rupture,
      early symptoms are those of a unilateral localized inflammatory condition with
      tenderness and swelling behind the medial malleolus of the ankle. Early diagnosis
      is a key factor in limiting patient disability.

PMID- 15960049
TI  - New horizons in orthopaedics: a rational discussion of biologics and bone graft
      substitutes.
AB  - Numerous inductive proteins, conductive substrates, and autogenous cellular
      concentration techniques have become clinically available as substitutes for
      autogenous bone graft. This review presents a critical analysis of their
      preclinical and clinical efficacy. In many instances, the widespread use of these
      materials must be questioned based on the limited clinical data available. A
      thorough knowledge of these materials is crucial for the surgeon to match the
      material to its defined indications.

PMID- 15960052
TI  - Nurses and the genomic revolution.
AB  - PURPOSE: To increase nurses' genetics and genomics literacy through a series of
      articles focused on genomic research discoveries and their importance for nursing
      education, practice, policy, and research. ORGANIZING FRAMEWORK: "Genomics for
      Health " is one of three themes, along with genomes to biology and genomes to
      society, emanating from applications of the Human Genome Project (HGP). METHODS:
      In this series of articles, nurse scientists who are experts in genetics and
      genomics sciences explain terminology, provide background information about the
      HGP, discuss clinical examples, and recommend changes in nursing practice,
      education, and research. CONCLUSIONS: The HGP has already led to major changes in
      clinical practice, research, education, and policy, and even more dramatic
      changes are predicted for people throughout the world. Mastering this information
      is necessary for nurses globally because genomic information will ultimately
      pervade all of health care.

PMID- 15960053
TI  - Nursing leadership in genomics for health and society.
AB  - PURPOSE: This article is part of the series regarding genomics and nursing
      practice, science, education, and policy. Issues in genetic testing, genetic
      information and the lessons learned through applications of genetic and genomic
      science are analyzed and discussed. FRAMEWORK: Scientists, scholars, and members
      of the public have articulated a vision to guide genomics research and
      scholarship. The three overarching themes of this conceptual framework are
      genomes to biology, genomes to health, and genomes to society. CONCLUSIONS:
      Nurses can promote the use of genomic research technologies and information in
      the context of health, biology, and society, as well as in nursing research,
      practice, education, and policy.

PMID- 15960054
TI  - The interface of genomic technologies and nursing.
AB  - PURPOSES: (a) to summarize views of the interface of technology, genomic
      technology, and nursing; (b) provide an overview of current and emerging genomic
      technologies; (c) present clinical exemplars of uses of genomic technology in two
      disease conditions; and (d) list genomic-focused nursing research on genomic
      technologies. ORGANIZING FRAMEWORK: A discussion of genomic technology in the
      context of nurses' views of technology, the importance of genomic technology for
      nurses, linking the central dogma of molecular biology to state-of-the-art tests
      and assays, and nurses' current use of technologies. CONCLUSIONS: Human genome
      discoveries will continue to be an integral part of disease prevention,
      diagnosis, treatment, and management. These discoveries also have the potential
      for being integrated into nursing science. Genomic technologies are becoming a
      driving force in patient management, so that nurses will be unable to provide
      quality care without knowledge of the types of genomic technologies, the
      rationale for their use, and the possible sequelae that can result from genetic
      diagnosis or treatment. Many nurses already are using genomic technologies to
      conduct genomic-focused nursing research. The biobehavioral nature of much of
      this research further indicates the important contributions of nurses in
      genomics.

PMID- 15960055
TI  - Quality of life and the concept of "living well" with HIV/AIDS in sub-Saharan
      Africa.
AB  - PURPOSE: To increase understanding of the meaning of quality of life for people
      living with HIV/AIDS in four countries in sub-Saharan Africa: Botswana, Lesotho,
      South Africa, and Swaziland. METHODS: Using a cross-sectional design and
      convenience sample, we administered a survey and collected data on demographic
      characteristics, measures of severity of illness, and perceptions of quality of
      life. The purposefully selected sample (N=743) consisted of community-based
      people living with HIV/AIDS in 2002. Based on the Wilson and Cleary framework for
      organizing variables related to quality of life, a hierarchical multiple
      regression was conducted with quality of life as the dependent variable. RESULTS:
      The sample of 743 persons was 61.2% female with a mean age of 34 years.
      Approximately 62 % of the sample reported having received an AIDS diagnosis. Ten
      predictor variables explained 53.2 % of the variance in life satisfaction. Those
      participants with higher life satisfaction scores were less educated, had worries
      about disclosure and finances, did not have an AIDS diagnosis or other comorbid
      conditions, had lower symptom intensity, had greater functioning, and had fewer
      health worries. None of these participants was taking antiretroviral medications
      at the time of this study. CONCLUSIONS: Several dimensions of the Wilson and
      Cleary model of quality of life were significantly related to life satisfaction
      for people living with HIV/AIDS in sub-Saharan Africa. Quality of life for this
      sample was primarily defined as overall functional ability and control over
      symptom intensity. These findings are similar to studies in developed countries
      that have shown the significant relationships among functional abilities, symptom
      control, and perceived quality of life. As antiretroviral medications become more
      available in these areas, community members and care providers can help clients
      realize the possibility of living well with HIV/AIDS, and can work with clients
      to improve functional ability and control symptom intensity to make living well a
      reality.

PMID- 15960056
TI  - Preparing nurses for the global pandemic of chronic obstructive pulmonary
      disease.
AB  - PURPOSE: To raise awareness of the global pandemic of chronic obstructive
      pulmonary disease (COPD), its multiple underlying causes, and how to fight it,
      with particular attention to needs in nursing education. METHODS: Integrative
      review of the literature. FINDINGS: The main underlying causes of COPD are both
      individual and environmental factors, and the disease usually results from an
      interaction between these two factors. The prevalence of COPD is highest in
      countries where cigarette smoking has been, or still is, very common, and it is
      lowest in countries where smoking is less common, or total tobacco consumption
      per person is low. COPD is to some extent a preventable disease especially by
      preventing exposure to tobacco smoke and to occupational dusts and chemicals
      including vapours, irritants, fumes, and indoor and outdoor air pollution. The
      main implication for nurses and nursing curricula is to expand the focus from the
      individual to include population-based intervention programmes. CONCLUSIONS:
      Addressing the underlying causes of COPD and providing appropriate interventions
      are within the scope of nursing practice and responsibility. Changes in nursing
      education are needed for nurses to be able to address the COPD pandemic.

PMID- 15960057
TI  - A model of consequences of need-driven, dementia-compromised behavior.
AB  - PURPOSE: To extend the original need-driven, dementia-compromised behavior (NDB)
      model by explaining the consequences of behavioral symptoms for the person with
      dementia. ORGANIZING CONSTRUCT AND METHODS: Literature is reviewed and the
      consequences of expressing needs through need-driven, dementia-compromised
      behaviors are posited. The consequences of need-driven, dementia-compromised
      behavior (C-NDB) theory is proposed as a framework to improve understanding of
      the person with dementia and the consequences of behavioral symptoms and unmet
      needs. FINDINGS: Instead of normative verbal communication, people with
      significant dementia commonly communicate need via non-normative behaviors,
      making it difficult for caregivers to know that the person has a need and the
      extent of such need. Not meeting needs of people with dementia affects the person
      with dementia, care factors, and contextual factors. Cascading effects occur in
      which not meeting the original need results in new needs and behavioral symptoms.
      CONCLUSIONS: This framework indicates the consequences of expressing need
      behaviorally rather than verbally and shows that caregiver actions might moderate
      the events that lead to many needs being unresolved. Suggestions are made
      regarding future research questions deduced from the model.

PMID- 15960058
TI  - Effects of nasogastric tube feeding on serum sodium, potassium, and glucose
      levels.
AB  - PURPOSE: To examine whether significant alterations in serum sodium, potassium,
      and glucose levels occurred after nasogastric tube feeding with iso-osmolar
      formula in acute brain infarction patients. DESIGN AND METHODS: Serum sodium,
      potassium, and glucose levels were analyzed by a retrospective medical record
      review of 85 nasogastric tube-fed patients. FINDINGS: The mean values of serum
      sodium and potassium levels on the day before, and 1st, 2nd, and 3rd days of
      nasogastric feeding were within the normal range. Alterations in the incidence
      rates of high, normal, and low level of serum sodium and potassium after tube
      feeding were not statistically significant. The mean blood glucose levels on the
      day before, and 1st, 2nd, and 3rd days of tube feeding were above normal, and the
      increase after tube feading was not statistically significant. CONCLUSIONS:
      Enteral tube feeding using iso-osmolar formula did not significantly alter serum
      sodium and potassium balance. However, most participants were hyperglycemic
      before and after tube feeding, indicating that hyperglycemia can be induced in
      the acute stages of brain infarction regardless of tube feeding.

PMID- 15960059
TI  - Hopelessness as a response to physical illness.
AB  - PURPOSE: To analyze hopelessness as a psychological response to physical illness,
      differentiate hopelessness from depression, and discuss measures of hopelessness.
      ORGANIZING FRAMEWORK: Walker and Avant's (1995) concept analysis strategy.
      METHOD: A review of the literature from 1983 to 2004 was completed, with a focus
      on hopelessness theory and measurement. FINDINGS: Although hopelessness is
      closely related to depression, distinct characteristics of hopelessness were
      identified. A continuum of attributes of hopelessness and depression was derived.
      Hopelessness has been examined in a variety of populations with several different
      instruments. One established measure was selected for discussion. CONCLUSIONS:
      Continued study of hopelessness as a psychological response to physical illness
      is needed, including the continued differentiation of hopelessness from
      depression, further analysis of the continuum of hopelessness and depression, and
      the differentiation of state from trait hopelessness. Research to validate this
      conceptualization will enhance accuracy of the diagnosis of hopelessness and
      testing of nursing inteventions.

PMID- 15960060
TI  - Processes of mental health service use by adolescents with depression.
AB  - PURPOSE: To begin development of a substantive theory of the processes of mental
      health service use by adolescents who are depressed and by their families.
      DESIGN: Grounded theory. METHODS: Open-ended interviews were conducted with 52
      young adults who were depressed as adolescents, four of their parents, and eight
      professionals who work with adolescents who are depressed. The constant
      comparison method was used to analyze the data. FINDINGS: Adolescents who are
      depressed and their families perceived several "treatment pitfalls" associated
      with formal mental health services: (a) "They'll (mental health clinicians) think
      I'm crazy," (b) "They'll tell my business," and (c) "They won't have a clue." The
      adolescents and their families interacted with the mental health care providers
      by engaging in the psychosocial process of "venturing through the system," that
      is, proceeding despite possible dangers and risks by steering clear, holding
      back, and letting it take hold. CONCLUSIONS: Mental health service use by
      adolescents with depression involved complex and fluid interactional processes
      among the depressed adolescents, their parents or caretakers, and mental health
      care providers. Strategies are needed to avoid creating the pitfalls that concern
      adolescents and their families.

PMID- 15960061
TI  - Factors influencing the use of registered nurse overtime in hospitals, 1995-2000.
AB  - PURPOSE: To assess nurse overtime in acute care general hospitals and the factors
      that influence overtime among various hospitals and in the same hospitals from
      year to year. METHODS: Staffing data from 1995 to 2000 from 193 acute general
      hospitals in New York State were used to examine hospital characteristics (size,
      location, RN unionization, hospital ownership, and teaching status) to determine
      whether they were associated with nurse overtime. RESULTS: The average weekly
      overtime RNs worked was 4.5% of total hours, varying from almost none to 16.6%.
      At mean overtime levels, nurses were working less overtime than the mean for
      manufacturing workers, but, at the extreme, nurses were working more than 6 hours
      overtime per week. Significant differences were observed in the use of overtime
      by hospital ownership and by union status. Nurses in government hospitals worked
      less overtime than did those in nongovernment hospitals. Nurses in unionized
      hospitals worked slightly more overtime than did nurses in nonunionized
      hospitals. CONCLUSIONS: Hospitals varied dramatically in their overtime use. That
      some categories of hospitals (e.g., government-owned) used little overtime
      indicates that hospital management can find substitutes for overtime to meet
      fluctuating staffing needs. The finding that hospitals with similar
      characteristics varied greatly in their number of overtime hours also supported
      this conclusion.

PMID- 15960062
TI  - Hospital ethical climates and registered nurses' turnover intentions.
AB  - PURPOSE: To investigate (a) the effects of hospital ethical climates on
      positional and professional turnover intentions of registered nurses, and (b) the
      relationships among demographic factors, employment characteristics, and
      positional and professional turnover intentions of registered nurses. DESIGN: A
      cross-sectional study of randomly selected registered nurses (n=463) in Missouri,
      USA, conducted in 2003 and 2004. METHODS: A self-administered questionnaire
      containing the Hospital Ethical Climate Survey, the Anticipated Turnover Scale,
      and the Nursing Retention Index was used to assess registered nurses' perceptions
      of the hospital ethical climate and their intentions to leave their position or
      the nursing profession. Descriptive statistics, Pearson product-moment
      correlations, and hierarchical regression techniques were used to analyze the
      data. FINDINGS: The hospital ethical climate explained 25.4% of the variance in
      positional turnover intentions and 14.7% of the variance in professional turnover
      intentions. Together, hospital ethical climate, control over practice, the use of
      educational reimbursement as a retention strategy, gender, and staff sufficiency
      explained 29.7% of the variance in positional turnover intentions. Hospital
      ethical climate, patient load, and control over practice together explained 15.8%
      of the variance in professional turnover intentions. CONCLUSIONS: Of the
      variables included in this analysis, the hospital ethical climate was most
      important in explaining nurses' positional and professional turnover intentions.

PMID- 15960063
TI  - APN-physician collaboration in caring for women with high-risk pregnancies.
AB  - PURPOSE: To examine: (a) frequency and focus of APN-physician collaborations in a
      clinical trial in which half of physician prenatal care for women with high-risk
      pregnancies was substituted with APN prenatal care delivered in women's homes;
      and (b) characteristics of women requiring greater numbers of collaborations.
      DESIGN AND METHODS: Descriptive study with secondary analysis of data from 83 of
      the original trial's 85 intervention participants followed by APNs prenatally
      through 8 weeks postpartum. APN practices, recorded in logs, included APN
      interactions with the women and the physician, and type of APN contact (e.g.,
      home visit, telephone call). Each APN-physician collaboration was coded for type,
      timing, and focus. FINDINGS: Total number of APN-physician collaboration contacts
      was 351, with a mean of 4.5 and a range of 1 to 16 per woman. Focus of
      collaborations was: status updates (59%), new physical findings (21%), change in
      treatment (8%), patient concerns (7%) and medication adjustment (5%). No
      significant differences in numbers of collaborations were found according to age,
      primary diagnosis, marital status, type of health insurance, race, or income.
      Women with high school education received more collaborations than did those not
      completing high school or those with some postsecondary education. Prenatally,
      women with a first pregnancy required more collaborations than did multipara
      participants. CONCLUSIONS: Most APN-physician collaborative contacts were focused
      on monitoring women's physical and emotional status and discussing new physical
      findings. These collaborations were important in the original trial's successful
      pregnancy and infant outcomes and savings in health care dollars.

PMID- 15960064
TI  - Education as a determinant of career retention and job satisfaction among
      registered nurses.
AB  - PURPOSE: To compare job satisfaction and career retention in two cohorts of RNs,
      those whose highest degrees were the associate degree (AD) or the bachelor's
      degree (BS) in nursing. DESIGN: Survey. METHODS: Instruments included a career
      satisfaction scale and questions based on the ongoing U.S. Health and Retirement
      Survey. Three-thousand nurses in the U.S. state of Vermont were surveyed with a
      resulting response rate of 56.7%. Of these respondents, 878 RNs fit the study
      criteria. FINDINGS: BS RNs started their nursing careers earlier, were employed
      longer, had held more positions, and in the largest age cohort (age 40-54), were
      more likely to have been in their current positions at least 10 years. BS RNs
      scored significantly higher in job satisfaction related to: (a) opportunity for
      autonomy and growth, (b) job stress and physical demands, and (c) job and
      organizational security. AD and BS nurses were not significantly different in
      their satisfaction with supervision; career, continuing education, and promotion
      opportunities; or pay and benefits. CONCLUSIONS: These findings indicate support
      of bachelor's level education for individual and social return on investment, and
      they show that AD education might have unintended consequences. Implications for
      the nursing shortage and educational policy are discussed.

PMID- 15960065
TI  - Expression of p53, DCC, and HER-2/neu in mucinous carcinoma of the breast.
AB  - We investigated the clinicopathologic and oncoprotein expression characteristics
      of 11 pure mucinous and 76 non-mucinous infiltrating ductal carcinomas in the
      human female breast. We compared patient age, tumor size, axillary lymph node
      status, and the expression of estrogen receptor (ER), progesterone receptor (PR),
      deleted-in-colon cancer (DCC), HER-2/neu, and p53. Mucinous carcinoma with
      axillary lymph node metastasis occurs less frequently than non-mucinous carcinoma
      (0% vs 63.1%; p = 0.0018). Compared with the non-mucinous type, mucinous
      carcinoma specimens have more DCC expression (100% vs 48.7%; p = 0.0027) and more
      ER expression (90.9% vs 26.9%; p = 0.0023), but less HER-2/neu overexpression (0%
      vs 38.1%; p = 0.0302). We confirmed that mucinous carcinoma samples from the
      breast reveal distinct clinicopathologic and oncoprotein expression features
      compared with non-mucinous carcinoma and, therefore, it seems reasonable to
      suggest different biologic characteristics and manifestations.

PMID- 15960066
TI  - Performance of thallium-201 electrocardiography-gated myocardial perfusion single
      photon emission computed tomography to assess left ventricular function.
AB  - This study evaluated the performance of gated single photon emission computed
      tomography (SPECT) with thallium-201 (201Tl) in assessing left ventricular
      ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume
      (ESV) in Taiwanese by determining repeatability and correlation with two
      dimensional (2D) echocardiography. A total of 18 patients underwent two
      sequential gated SPECT acquisitions within 30 minutes in the resting state to
      assess repeatability. Another 28 patients who underwent gated SPECT and 2D
      echocardiography within 7 days were included for comparison. The two sequential
      measurements were well correlated with respect to LVEF, EDV, and ESV (r = 0.97,
      0.95, and 0.97, respectively, all p < 0.0001). Bland-Altman analysis revealed
      that two standard deviations of the absolute difference between the two
      sequential measurements for LVEF, EDV, and ESV were 6.4%, 16.8 mL, and 8.6 mL,
      respectively. For LVEF, EDV, and ESV, correlations between redistribution 201Tl
      gated SPECT and echocardiography were also excellent (all r = 0.83, p < 0.0001).
      LVEF was similar with 201Tl-gated SPECT and echocardiography, but EDV and ESV
      were significantly higher with echocardiography (p < 0.05). Our study revealed
      that 201Tl-gated SPECT has high repeatability and excellent correlation with
      echocardiography for the assessment of LVEF and volumes in Taiwanese. These
      results support the clinical application of gated SPECT in routine 201Tl
      myocardial perfusion imaging in Taiwanese.

PMID- 15960067
TI  - Predicting the grade of disabilty 1 year after stroke following rehabilitation.
AB  - The purpose of this study was to identify predictors of grades of disability at
      least 1 year after stroke rehabilitation therapy. We recruited stroke patients
      from the inpatient rehabilitation department of a university hospital. The degree
      of disability was graded using the disability evaluation at least 1 year after
      stroke onset. Functional ability was evaluated using the Functional Independence
      Measure instrument on admission, on discharge from the inpatient rehabilitation
      program, and at the 6-month follow-up visit after discharge. Major
      sociodemographic, medical, and rehabilitative factors were also collected during
      the hospitalization period. Of the 109 patients surveyed, 64 (58.7%) had severe
      or very severe grades of disability. The correlates of severe or very severe
      disability in logistic regression analyses were bilaterally affected (odds ratio,
      OR, 10.8), impaired orientation (OR, 3.6), and poorer functional ability at
      discharge (OR, 7.6). Based on the significant predictors identified, the logistic
      regression model correctly classified severe or very severe disability in 68.0%
      of subjects. The higher frequency of severe or very severe disability in this
      study may have been due to the relatively more severely affected stroke patient
      population in the inpatient rehabilitation service and the use of unique
      disability evaluation criteria. These results may provide information useful in
      planning continuous rehabilitation care and setting relevant socio-welfare
      policies for stroke victims.

PMID- 15960068
TI  - Investigation of management models in elite athlete injuries.
AB  - This cross-sectional study investigated management models among elite athletes
      participating in sports including baseball, basketball, soccer, volleyball,
      tennis, softball, football, handball, track and field, swimming, judo, tae-kwon
      do, gymnastics, archery, and weight lifting at the Tsoying National Sport
      Training Center. Data were collected by questionnaire. Of the 393 athletes
      investigated, 56% were male and 44% were female, with an average age of 20.9
      years and average length of athletic experience of 9.8 years. At the time of the
      survey, 74.8% had sporting injuries and were being treated with Chinese and/or
      Western medicine. Among injured athletes, 14.5% chose Western treatment, 8.1%
      chose Chinese medicine, and 75.4% received combined treatment. There were various
      reasons for choosing the management model. Most athletes had ordinary self
      recognition of sports injury prevention. Their qualified ability for sports
      injury prevention was 70%. This ability was significantly correlated with age,
      education, and sports experience. Within Taiwan's current medical and social
      environment, elite athletes prefer a combination of Eastern and Western
      treatments for sports injuries. Each of the medical approaches are widely
      accepted by elite athletes and their coaches. Doctors trained in Western medicine
      should learn these alternative treatment methods and apply them effectively in
      athletes, so that a better medical network can be established.

PMID- 15960070
TI  - Rare extra-articular manifestation of rheumatoid arthritis: scleromalacia
      perforans.
AB  - Rheumatoid arthritis is a systemic disease with manifestations in many organs. In
      most cases, involvement of the locomotor system dominates the clinical picture.
      However, extra-articular manifestations can be detected in almost any organ
      system with varied incidence in different series. Ophthalmic presentations
      include Sjogren's syndrome, episcleritis, and scleritis. The most severe form of
      scleritis, scleromalacia perforans, is a very rare ophthalmic manifestation. We
      present the case of a 60-year-old man who had had rheumatoid arthritis for more
      than 10 years. He had scleromalacia perforans but no other extra-articular
      manifestations.

PMID- 15960069
TI  - Allopurinol-induced severe hypersensitivity with acute renal failure.
AB  - A 62-year-old male was sent to the emergency room due to a high fever and
      generalized skin rash after taking allopurinol for 9 days. Physical examination
      was normal except for the generalized skin rash presenting with erythematous
      macules. Complete blood count showed leukocytosis with eosinophilia. Blood
      biochemistry showed impaired renal and hepatic function. Pathologic examination
      concluded that the skin rash was erythema multiforme. These findings met the
      diagnostic criteria for allopurinol-induced hypersensitivity syndrome (AHS). Our
      patient not only had the most common skin lesion but soon developed acute renal
      failure that required intermittent hemodialysis, despite rapid discontinuation of
      allopurinol and adequate hydration and steroid therapy. No other causes of acute
      renal failure were found. Renal impairment was the worst part of the patient's
      condition and he never completely recovered. AHS should be considered in the
      differential diagnosis of acute renal and hepatic failure in patients with
      evidence of allergy and recent use of allopurinol.

PMID- 15960071
TI  - Right ventricle-dependent coronary circulation in pulmonary atresia with intact
      ventricular septum: a case report.
AB  - Pulmonary atresia with intact ventricular septum (PAIVS) is a morphologically
      heterogeneous lesion and accounts for 1-3% of critically ill infants with
      congenital heart disease. Numerous surgical approaches have been attempted with
      varying degrees of success, but the mortality rate is still high in most series.
      The optimal surgical procedure depends on the size and morphology of the
      tricuspid valve and right ventricle and the presence or absence of right
      ventricle-dependent coronary circulation. Therefore, it is pivotal to define the
      precise morphologic and hemodynamic characteristics, especially coronary artery
      anatomy. In this report, we describe a full-term female neonate with cyanosis
      soon after birth. Two-dimensional and color Doppler echocardiography corroborated
      the diagnosis of PAIVS and showed a small right ventricle. Cardiac
      catheterization indicated PAIVS and further revealed right ventricle-dependent
      coronary circulation. A systemic-to-pulmonary artery shunt was constructed with a
      positive immediate result.

PMID- 15960072
TI  - Encapsulated columnar-cell carcinoma of the thyroid: a case report.
AB  - Columnar-cell carcinoma is a rare form of papillary thyroid carcinoma. It is a
      biologically aggressive variant, according to the World Health Organization
      classification, due to its rapid growth, high local recurrence rate, and frequent
      lung, brain, and bone metastases. However, recent reports indicate encapsulated
      tumors confined to the thyroid gland are associated with a more favorable
      prognosis. We report a case of encapsulated columnar-cell carcinoma occurring in
      the right lobe of the thyroid in a 25-year-old female and discuss the
      histopathologic features, differential diagnosis, and prognostic factors.

PMID- 15960073
TI  - Ventricular tachycardia and spontaneous rupture of an extra-adrenal
      pheochromocytoma case.

PMID- 15960074
TI  - Conjugate of bovine hemoglobin and human serum albumin as a candidate for blood
      substitute: characteristics and effects on rats.
AB  - Conjugate of bovine hemoglobin (bHb) and human serum albumin (HSA) was prepared.
      The product was simply composed of 89.7% one-to-one Hb-HSA conjugate, 6.0%
      oligomer of Hb and HSA, 3.5% unconjugated HSA and 0.8% unconjugated Hb, with an
      average molecular weight of 157 kD. The physicochemical characteristics were
      determined. Effects of single replacement on blood pressure and long-term
      survival of rats with 30% and 60% acute blood loss were studied, in comparison
      with Ringer-lactate solution, stroma-free hemoglobin (SFHb), 5% HSA in Ringer
      lactate, whole blood and no resuscitation fluid. Results showed that Hb-HSA
      conjugate maintained the mean arterial pressure of rats to initial level with no
      pressor effect. Long-term effects of the replacement fluids on 30% bleeding rats
      showed that, for the group infused with Hb-HSA conjugate, histology of five major
      organs, heart, kidney, liver, spleen and lung, were essentially normal, similar
      to that of whole blood, while obviously renal side-effects appeared in other
      groups. The efficacy of the conjugate was further demonstrated by the
      resuscitation of lethal hemorrhagic shock rats (60% acute blood loss) with 100%
      survival rate (followed for 14 days), the same result as whole blood. The Hb-HSA
      conjugate can thus be another candidate for blood substitute in emergency.

PMID- 15960075
TI  - Effects of hemoglobin vesicles on resting and agonist-stimulated human platelets
      in vitro.
AB  - Hemoglobin vesicles (HbV) are artificial oxygen carriers that encapsulate a
      concentrated hemoglobin (Hb) solution with a phospholipid bilayer membrane. The
      oxygen transporting ability of HbV in vivo has been demonstrated by the
      transfusion of HbV into hemorrhagic shock rodent models. However, the
      compatibility of HbV with human blood cells must be evaluated. Preincubation of
      platelets with concentrations of 20% or 40% HbV had no effect on the binding of
      PAC-1, a monoclonal antibody that detects activation-dependent conformational
      changes in alphaIIbbeta3 on platelets, or the surface expression of CD62P in
      whole blood. ADP-induced increases in PAC-1 binding were significantly enhanced
      by exposing the platelets to concentrations of either 20% or 40% HbV, whereas the
      ADP-induced increases in CD62P expression were not affected by HbV treatment at
      either concentration. Preincubation of platelet-rich plasma (PRP) with HbV
      minimally reduced the spontaneous release of TXB2 and RANTES, but did not
      significantly affect the formation of TXB2 or the release of RANTES and beta-TG
      in platelets stimulated with ADP. Similarly, preincubation of PRP with HbV
      minimally reduced the spontaneous release of RANTES but did not significantly
      affect the formation of TXB2 or the release of RANTES and beta-TG in platelets
      stimulated with collagen, although collagen-induced serotonin release tended to
      decrease with HbV pretreatment. These data suggest that the exposure of human
      platelets to high concentrations of HbV (up to 40%) in vitro did not cause
      platelet activation and did not adversely affect the formation and secretion of
      prothrombotic substances or proinflammatory substances triggered by platelet
      agonists, although one of the earliest events in ADP-induced platelet activation
      was slightly potentiated by HbV pretreatment at the doses tested. Taken together,
      these results imply that HbV, at concentrations of up to 40%, do not have any
      aberrant interactions with either unstimulated or agonist-induced platelets.

PMID- 15960076
TI  - Stability of liposome encapsulated hemoglobin dispersions.
AB  - The demand for artificial blood substitutes in cases of elective surgeries,
      trauma, and civilian mass catastrophes increases every day. However, few studies
      have been done to characterize the mechanical stability of blood substitutes,
      especially liposome encapsulated hemoglobin (LEHb) dispersions. In this work, the
      stability of LEHb dispersions was investigated by fitting Jung et al.'s liposome
      size distribution model to experimentally measured LEHb size distributions [6]
      (produced via extrusion) using asymmetric flow field-flow fractionation coupled
      with multi-angle static light scattering. The effective bending constant (KB) and
      radius of curvature (R0) of each liposome dispersion were regressed from the size
      distribution fits. The model was found to be in agreement with the size
      distributions of LEHbs extruded through 400, 200 and 100 nm pore diameter
      membranes, but not in agreement with LEHbs extruded through 80 and 50 nm pore
      diameter membranes. Although the magnitude of KB fluctuated, we deduced a general
      trend for KB to decrease with decreasing pore diameter, and increasing initial Hb
      concentration. LEHbs extruded through 400nm pore diameter membranes were
      stabilized by the spontaneous curvature effect, while those extruded through 80
      and 50 nm pore diameter membranes were mostly stabilized by thermal undulations,
      regardless of the initial Hb concentration. For LEHb dispersions extruded through
      200 and 100 nm pore diameter membranes, there was a transition of stabilization
      mechanism from spontaneous curvature to thermal undulations with increasing
      initial Hb concentration. Taken together, these results suggest that moderate Hb
      encapsulation might actually impart better mechanical stability to LEHb
      dispersions extruded through 200 and 100 nm pore diameter membranes.

PMID- 15960077
TI  - Physical properties and stability mechanisms of poly(ethylene glycol) conjugated
      liposome encapsulated hemoglobin dispersions.
AB  - Liposomes encapsulating hemoglobin (LEHs) surface-conjugated with 2000 and 550 Da
      poly(ethylene glycol) (PEG) were produced via extrusion through 400, 200 and 100
      nm pore diameter membranes in two types of phosphate buffer with different ionic
      strengths. The lipid bilayers were composed of dimyristoyl-phosphatidylcholine
      (DMPC), cholesterol, dimyristoyl-phosphoethanolamine-PEG (DMPE-PEG), dimyristoyl
      phosphatidylglycerol (DMPG), and alpha-tocopherol (in a 43:40:10:5:2 mole ratio).
      N-acetyl-L-cysteine was coencapsulated in order to suppress hemoglobin (Hb)
      oxidation. Various physical properties of PEG-LEH dispersions were determined:
      size distribution, encapsulation efficiency, P50 (partial pressure of O2 where
      half of the oxygen binding sites are saturated with O2), cooperativity
      coefficient, and encapsulated methemoglobin (MetHb) level. In order to study the
      stabilization mechanism of these dispersions, the effective bending constant (KB)
      and the spontaneous radius of curvature (R0) of PEG-LEHs were extracted by
      fitting a mathematical model describing the size distribution of a liposome
      dispersion to the experimentally measured size distributions. We observed that
      liposome dispersions extruded in phosphate buffer (PB) were more monodisperse
      than liposomes extruded in phosphate buffered saline (PBS), and higher molecular
      weight PEG promoted the formation of narrower size distributions. Moreover,
      extrusion in PB and lipid conjugation with higher molecular weight PEG imparted
      higher bilayer rigidity (high KB), and stabilized the liposome dispersions by the
      spontaneous curvature mechanism, whereas the other liposome dispersions were
      stabilized by thermal undulations (low KB). The P50 and cooperativity coefficient
      of PEG-LEHs extruded in PBS and PB was comparable to that of human blood, and the
      encapsulated MetHb levels were less than 5%. The highest encapsulation
      efficiencies obtained were 27%-36% (82-109 mg Hb/mL) for LEH dispersions extruded
      in PBS and grafted with 2000 Da PEG. These dispersions yielded KBs' ranging from
      7kT to 27kT, which indicated that these dispersions were stabilized by
      spontaneous curvature. Whereas the same lipid combination extruded in PBS,
      however, instead conjugated with 550 Da PEG resulted in KBs' ranging from 2 kT to
      2.7 kT, which indicated that these dispersions were stabilized by thermal
      undulations. Thermal undulations permitted Hb leakage through the lipid bilayers,
      which in turn lowered the encapsulation efficiency to 1%-10.7% (3-32 mg Hb/mL).
      Taken together, the experimentally measured size distributions and encapsulation
      efficiencies of PEG-LEH dispersions can be readily explained through analysis of
      the magnitude of KB, which dictates the stability mechanism of the liposome
      dispersion.

PMID- 15960078
TI  - Effects of phosphorothioate oligodeoxynucleotide on hemoglobin-induced damage to
      intestinal mucosa.
AB  - Some "blood substitutes," such as human diaspirin cross-linked hemoglobin DBBF
      Hb, can damage the intestinal mucosa. This response may be due to release of free
      iron from Hb leading to production of reactive oxygen species (ROS).
      Phosphorothioate oligodeoxynucleotides can bind and sequester iron. Therefore
      experiments were performed to test whether PS-ODN, composed of ten consecutive
      cytidines "C-10," reduces Hb-induced ROS generation and damage in the mucosa.
      Anesthetized Sprague-Dawley rats (4-6 per group) were injected arterially with 1
      mg C-10, followed two minutes later by 50 mg DBBF-Hb. The positive controls
      received only DBBF-Hb and the negative controls either saline or PS-ODN followed
      by saline. Either ROS formation was monitored using a fluorescence technique, or
      the intestine was fixed for microscopy after 8 or 30 min. Sixty villi per rat
      were assigned an epithelial integrity index (EI), ranging from 1 (intact) to 3
      (some cell-cell and cell-basement membrane separation). Pretreatment with PS-ODN
      significantly exacerbated DBBF-Hb-induced ROS formation, and PS-ODN groups showed
      significantly more epithelial damage near Peyer's patches, (EI of 1.93 +/- 0.06
      (SEM) at 8 minutes and 1.31 +/- 0.04 at thirty minutes), than the negative
      controls, (1.11 +/- 0.02 at both 8 and 30 minutes), or the positive controls
      (1.43 +/- 0.05 at 8 minutes and 1.20 +/- 0.03 at 30 minutes) (p < 0.05). However,
      mast cell degranulation, eosinophil accumulation and goblet cell secretion were
      significantly reduced in the DBBF-Hb groups pre-treated with PS-ODN. Thus, PS
      ODN, although an iron chelator, can significantly enhance epithelial damage
      caused by DBBF-Hb in the rat intestinal mucosa near Peyer's patches, possibly by
      formation of the ferryl component of the hemoglobin.

PMID- 15960079
TI  - Recombinant Clostridium perfringens alpha-N-acetylgalactosaminidase blood group
      A2 degrading activity.

PMID- 15960080
TI  - Ameliorating effect of phytoestrogens on CCl4-induced oxidative stress in the
      livers of male Wistar rats.
AB  - Glutathione-S-transferases and glutathione play a key role in the detoxification
      of most toxic agents. In the present study, the protective effects, if any, of
      isoflavone phytoestrogens--genistein and daidzein on the carbon tetrachloride
      (CCl4) induced changes in the activity of alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), glutathione S transferase (GSH) and levels of
      glutathione (GSH) and thiobarbituric acid reactive substances (TBARS)-were
      studied. The activities of ALT and AST were assayed in the serum, whereas the
      activity of GST and levels of GSH and TBARS were determined in the livers of
      rats. The current study involved the division of animals into two main groups:
      (i) rats pretreated with genistein and daidzein for three days; and (ii) non
      pretreated rats. In the pretreated group, rats received oral doses of genistein
      (7.9 micromol/kg body weight) and daidzein (7.9 micromol/kg body weight) for
      three consecutive days (once daily) followed by oral dose of CCl4 on the 4th and
      the 5th day concurrently with the phytoestrogens-genistein or daidzein. In the
      non-pretreated group animals received oral dose of CCl4 (1 ml/kg body weight) for
      two consecutive days along with the phytoestrogens-genistein or daidzein.
      Treatment of male rats with CCl4 significantly elevated the activity of ALT and
      AST in serum and levels of TBARS in the liver. On the other hand, CCl4 resulted
      in decreased activity of GST and lowered the GSH levels. Coadministration of
      genistein and daidzein with CCl4 could not restore the alterations in the
      activity of ALT and AST caused by CCl4 to normal control levels. However,
      repeated dose treatments with genistein and daidzein for three days prior to the
      administration of CCl4 restored such alterations to normal levels. Our results
      indicate that genistein is more effective than daidzein in counteracting the
      inhibition of GST activity caused by CCl4 and restoring it to normal levels.
      Genistein was also more effective than daidzein restoring the induced TBARS
      levels caused by CCl4 to normal control levels when rats were pretreated with the
      isoflavone orally for three days. It has been observed that the tested
      isoflavonoids were able to antagonize the toxic effects of CCl4. Such
      counteracting effects were more pronounced for genistein and when the
      phytoestrogens were administered as repeated doses prior CCl4 administration.

PMID- 15960081
TI  - Study on modification of collagen with chondroitin sulfate on the microcosmic
      level.
AB  - To observe the changes during the process of modificating collagen with
      chondroitin sulfate (CS), a series of experiments was designed. Collagen scaffold
      was constructed by lyophilization. CS was attached into the scaffold through
      crosslinking. Solid-liquid phase separation method was used to shape 3D porous
      structure. Both kinds of scaffolds were investigated by Transmission Electron
      Microscopy (TEM), Scanning Electron Microscopy (SEM), and Electron Spectroscopy
      for Chemical Analysis (ESCA), Amino Acid Analyses (AAA), and so on for structures
      and characteristics. The results showed that CS could improve the properties of
      collagen both in biocompatibility and mechanical property. It increased the polar
      groups on the surface of scaffold and protected amino acid residues of collagen
      fiber. At the same time, the structure of scaffold became more regular because of
      the increase of polar groups. It was indicated that those were the real reasons
      for the improvement of modification.

PMID- 15960082
TI  - Preparation of adsorbents for the removal of endotoxin.
AB  - By using the agar beads as the support, L-lysine as the ligand, three kinds of
      absorbents with different spacers for removal of endotoxin were prepared. The
      adsorption capacity of three adsorbents was compared. Among them, Ag3, with L
      lysine ligand and hexamethylendiamine as the spacer, was the best in adsorption
      capacity and was selected for hemoperfusion on rabbits. The results showed the
      level of endotoxin in endotoxemia rabbit after hemoperfusion was near normal
      level. The clearance percentage of endotoxin was 73.6%

PMID- 15960083
TI  - Interruption management: the use of attention-directing tactile cues.
AB  - Previous research has suggested that providing informative cues about
      interrupting stimuli aids management of multiple tasks. However, auditory and
      visual cues can be ineffective in certain situations. The objective of the
      present study was to explore whether attention-directing tactile cues aid or
      interfere with performance. A two-group posttest-only randomized experiment was
      conducted. Sixty-one participants completed a 30-min performance session
      consisting of aircraft-monitoring and gauge-reading computer tasks. Tactile
      signals were administered to a treatment group to indicate the arrival and
      location of interrupting tasks. Control participants had to remember to visually
      check for the interrupting tasks. Participants in the treatment group responded
      to more interrupting tasks and responded faster than did control participants.
      Groups did not differ on error rates for the interrupting tasks, performance of
      the primary task, or subjective workload perceptions. In the context of the tasks
      used in the present research, tactile cues allowed participants to effectively
      direct attention where needed without disrupting ongoing information processing.
      Tactile cues should be explored in a variety of other visual, interrupt-laden
      environments. Potential applications exist for aviation, user-interface design,
      vigilance tasks, and team environments.

PMID- 15960084
TI  - Designing effective human-automation-plant interfaces: a control-theoretic
      perspective.
AB  - In this article, we propose the application of a control-theoretic framework to
      human-automation interaction. The framework consists of a set of conceptual
      distinctions that should be respected in automation research and design. We
      demonstrate how existing automation interface designs in some nuclear plants fail
      to recognize these distinctions. We further show the value of the approach by
      applying it to modes of automation. The design guidelines that have been proposed
      in the automation literature are evaluated from the perspective of the framework.
      This comparison shows that the framework reveals insights that are frequently
      overlooked in this literature. A new set of design guidelines is introduced that
      builds upon the contributions of previous research and draws complementary
      insights from the control-theoretic framework. The result is a coherent and
      systematic approach to the design of human-automation-plant interfaces that will
      yield more concrete design criteria and a broader set of design tools.
      Applications of this research include improving the effectiveness of human
      automation interaction design and the relevance of human-automation interaction
      research.

PMID- 15960085
TI  - Automation in future air traffic management: effects of decision aid reliability
      on controller performance and mental workload.
AB  - Future air traffic management concepts envisage shared decision-making
      responsibilities between controllers and pilots, necessitating that controllers
      be supported by automated decision aids. Even as automation tools are being
      introduced, however, their impact on the air traffic controller is not well
      understood. The present experiments examined the effects of an aircraft-to
      aircraft conflict decision aid on performance and mental workload of experienced,
      full-performance level controllers in a simulated Free Flight environment.
      Performance was examined with both reliable (Experiment 1) and inaccurate
      automation (Experiment 2). The aid improved controller performance and reduced
      mental workload when it functioned reliably. However, detection of a particular
      conflict was better under manual conditions than under automated conditions when
      the automation was imperfect. Potential or actual applications of the results
      include the design of automation and procedures for future air traffic control
      systems.

PMID- 15960086
TI  - Effects of automation of information-processing functions on teamwork.
AB  - We investigated the effects of automation as applied to different stages of
      information processing on team performance in a complex decision-making task.
      Forty teams of 2 individuals performed a simulated Theater Defense Task. Four
      automation conditions were simulated with computer assistance applied to
      realistic combinations of information acquisition, information analysis, and
      decision selection functions across two levels of task difficulty. Multiple
      measures of team effectiveness and team coordination were used. Results indicated
      different forms of automation have different effects on teamwork. Compared with a
      baseline condition, an increase in automation of information acquisition led to
      an increase in the ratio of information transferred to information requested; an
      increase in automation of information analysis resulted in higher team
      coordination ratings; and automation of decision selection led to better team
      effectiveness under low levels of task difficulty but at the cost of higher
      workload. The results support the use of early and intermediate forms of
      automation related to acquisition and analysis of information in the design of
      team tasks. Decision-making automation may provide benefits in more limited
      contexts. Applications of this research include the design and evaluation of
      automation in team environments.

PMID- 15960087
TI  - Thumb force and muscle loads are influenced by the design of a mechanical pipette
      and by pipetting tasks.
AB  - Work involving pipetting is associated with elevated rates of musculoskeletal
      disorders of the hand and wrist. The purpose of this study was to quantify thumb
      loading and muscle activity and determine if they varied among pipetting tasks.
      Fourteen experienced participants performed nine pipetting tasks while surface
      electromyography was measured for the extensor pollicis brevis, abductor pollicis
      longus, flexor pollicis longus, and abductor pollicis brevis muscles. For five
      tasks, participants used a pipette instrumented to measure the thumb force
      applied to the plunger. High-precision tasks significantly increased static
      muscle activity but reduced peak thumb force on average 5% as compared with low
      precision tasks. Pipetting high-viscosity fluids increased peak thumb forces on
      average 11% as compared with pipetting low-viscosity fluids. Use of a latch
      pipette increased muscle activity of three muscles. We conclude that pipette
      design and pipetting tasks can influence applied thumb force and muscle activity.
      We recommend that pipettes be designed to limit applied peak forces and that
      pipette users be instructed in use patterns that will reduce applied forces.
      Actual or potential applications of this research include modifications to
      pipette designs and worker training in order to reduce hand pain associated with
      pipetting.

PMID- 15960088
TI  - A tool to assess the comfort of wearable computers.
AB  - Wearable computer comfort can be affected by numerous factors, making its
      assessment based on one value with one scale inappropriate. This paper presents a
      tool that measures wearable comfort across six dimensions: emotion, attachment,
      harm, perceived change, movement, and anxiety. The dimensions for these comfort
      rating scales were specifically developed for wearable equipment assessment by
      applying multidimensional scaling to a comfort term association matrix developed
      using the results of groupings of wearable computer comfort terms. Testing the
      scales on four different types of wearable computer showed that the scales can be
      used to highlight differences in comfort between different types of technology
      for different aspects of comfort. An intraclass correlation of .872 suggested
      that the scales were used with a high level of reliability. A second study showed
      that modifications made to a wearable computer resulted in improvements in
      comfort, although they were not significant (p > .05). A potential application
      for this research is as an aid to designers and researchers for assessing the
      wearability, in terms of comfort, of wearable computer devices and to determine
      the effectiveness of any modifications made to the design of a wearable device.

PMID- 15960089
TI  - Task workload and cognitive abilities in dynamic decision making.
AB  - Researchers often treat workload as a task-dependent variable. To evaluate the
      effect of workload on individuals' performance, researchers commonly use several
      methods, such as varying the complexity or number of tasks that test participants
      are asked to handle or placing individuals under time constraints. Only rarely
      have researchers investigated workload as a variable dependent on individuals'
      cognitive abilities. This study investigated workload during dynamic decision
      making in terms of its dependence on both task workload and cognitive abilities.
      The findings demonstrate detrimental effects of both high task workload and low
      cognitive abilities. Further, the results show that high workload is more
      detrimental in individuals with low cognitive abilities than in individuals with
      high cognitive abilities. Potential applications of this research include the
      design of new workload studies and new training protocols in which psychometric
      tests are used.

PMID- 15960090
TI  - Warrants for prescription: analytically and empirically based approaches to
      improving decision making.
AB  - Efforts to improve decision making must appeal to some source of warrant - that
      is, specific criteria or models for guiding and evaluating decision-making
      performance. We examine and compare the warrants for two approaches to decision
      aids, decision training, and consulting: analytically based prescription, which
      obtains warrant from formal models, and empirically based prescription, which
      obtains warrant from descriptive models of successful performance. We argue that
      empirically based warrants can provide a meaningful and valid basis for
      prescriptive intervention without committing the naturalistic fallacy (i.e.,
      confusing what is with what ought to be) and without the use of formal deduction
      from first principles. We describe points of divergence as well as convergence in
      the types of warrant appealed to by naturalistic decision making and decision
      analysis, letting each approach shed light on the other, and explore the
      application of empirically based prescription to cognitive engineering. Actual or
      potential applications of this research include the development of training
      programs to improve various aspects of naturalistic decision making.

PMID- 15960091
TI  - Configural displays can improve nutrition-related. decisions: an application of
      the proximity compatibility principle.
AB  - The nutrition label format currently used by consumers to make dietary-related
      decisions presents significant information-processing demands for integration
      based decisions; however, those demands were not considered as primary factors
      when the format was adopted. Labels designed in accordance with known principles
      of cognitive psychology might enhance the kind of decision making that food
      labeling was intended to facilitate. Three experiments were designed on the basis
      of the proximity compatibility principle (PCP) to investigate the relationship
      between nutrition label format and decision making; the experiments involved two
      types of integration decisions and one type of filtering decision. Based on the
      PCP, decision performance was measured to test the overall hypothesis that
      matched task-display tandems would result in better decision performance than
      would mismatched tandems. In each experiment, a statistically significant
      increase in mean decision performance was found when the display design was
      cognitively matched to the demands of the task. Combined, the results from all
      three experiments support the general hypothesis that task-display matching is a
      design principle that may enhance the utility of nutrition labeling in nutrition
      related decision making. Actual or potential applications of this research
      include developing robust display solutions that aid in less effortful
      assimilation of nutrition-related information for consumers.

PMID- 15960092
TI  - Objects and mappings: incompatible principles of display design - a critique of
      Marino and Mahan.
AB  - Representation aiding (and similar approaches that share the general orientation)
      has a great deal of utility, predictive ability, and explanatory power. Marino
      and Mahan (2005) discuss principles that are critical to the RA approach
      (configurality, emergent features, and mappings) in a reasonable fashion.
      However, the application of these principles is far from reasonable. The authors
      explicitly realize the potential for interactions between nutrients: "The
      nutritional quality of a food product is a multidimensional concept, and higher
      order interactions between nutrients may exist" (p. 126). However, they made no
      effort to discover the nature of these interactions: "No attempt was made to
      identify contingent interactions between nutrients" (p. 126). Despite not knowing
      the nature of the interactions between nutrients, they purposely chose a highly
      configural display that produced numerous emergent features dependent upon these
      interactions: "A radial spoke display was selected because of the strong
      configural properties of such display formats (Bennett & Flach, 1992)" (p. 124).
      Finally, the authors show apparent disdain for the specific mappings among
      domain, agent, and display that are fundamental to the RA approach: "[O]ther
      configural display formats could have been used" (p. 124). It is impossible to
      reconcile these statements and the RA approach to display design. However, these
      statements make perfect sense if a perceptual object is a guiding principle in
      one's approach to display design. Marino and Mahan (2005) draw heavily upon the
      principle of a perceptual object in their design justifications, experimental
      predictions, and interpretations of results. As we have indicated here and
      elsewhere (Bennett & Flach, 1992), we believe that these two sets of organizing
      principles for display design (i.e., objects and mappings) are incompatible.
      Display design will never be an exact science; there will always be elements of
      art and creativity. However, the guiding principles have moved well beyond the
      simple strategy of throwing variables into a geometric object format and relying
      upon the human agent's powerful perceptual systems to carry the design.

PMID- 15960093
TI  - The impact of visual layout factors on performance in Web pages: a cross-language
      study.
AB  - Visual layout has a strong impact on performance and is a critical factor in the
      design of graphical user interfaces (GUIs) and Web pages. Many design guidelines
      employed in Web page design were inherited from human performance literature and
      GUI design studies and practices. However, few studies have investigated the more
      specific patterns of performance with Web pages that may reflect some differences
      between Web page and GUI design. We investigated interactions among four visual
      layout factors in Web page design (quantity of links, alignment, grouping
      indications, and density) in two experiments: one with pages in Hebrew, entailing
      right-to-left reading, and the other with English pages, entailing left-to-right
      reading. Some performance patterns (measured by search times and eye movements)
      were similar between languages. Performance was particularly poor in pages with
      many links and variable densities, but it improved with the presence of uniform
      density. Alignment was not shown to be a performance-enhancing factor. The
      findings are discussed in terms of the similarities and differences in the impact
      of layout factors between GUIs and Web pages. Actual or potential applications of
      this research include specific guidelines for Web page design.

PMID- 15960094
TI  - Children using cellular phones: the effects of shortcomings in user interface
      design.
AB  - Differences in cellular phones' complexity and their impact on children's
      performance are under study in this experiment. Twenty children (age 9-14 years)
      solved tasks on two phones that were simulated according to existing models on a
      PC with a touch screen, holding constant display size, fonts, and colors. Actions
      were logged and analyzed regarding execution time, detour steps, and specific
      errors. Results show that children using the Siemens C35i with 25% higher
      complexity (with regard to number of required production rules) spent double the
      time solving tasks and undertook three times as many detour steps as children
      using the less complex Nokia 3210. A detailed analysis of user actions revealed
      that the number of production rules to be learned fails to account for most
      difficulties. Instead, ambiguous naming, poor categorization of functions, and
      unclear functionality of keys undermined performance. Actual or potential
      applications of this research include guidelines to improve the usability of all
      devices with small displays and hierarchical menu structures, such as cellular
      phones.

PMID- 15960095
TI  - Interacting with notebook input devices: an analysis of motor performance and
      users' expertise.
AB  - In the present study the usability of two different types of notebook input
      devices was examined. The independent variables were input device (touchpad vs.
      mini-joystick) and user expertise (expert vs. novice state). There were 30
      participants, of whom 15 were touchpad experts and the other 15 were mini
      joystick experts. The experimental tasks were a point-click task (Experiment 1)
      and a point-drag-drop task (Experiment 2). Dependent variables were the time and
      accuracy of cursor control. To assess carryover effects, we had the participants
      complete both experiments, using not only the input device for which they were
      experts but also the device for which they were novices. Results showed the
      touchpad performance to be clearly superior to mini-joystick performance.
      Overall, experts showed better performance than did novices. The significant
      interaction of input device and expertise showed that the use of an unknown
      device is difficult, but only for touchpad experts, who were remarkably slower
      and less accurate when using a mini-joystick. Actual and potential applications
      of this research include an evaluation of current notebook input devices. The
      outcomes allow ergonomic guidelines to be derived for optimized usage and design
      of the mini-joystick and touchpad devices.

PMID- 15960096
TI  - The impact of hearing protection on sound localization and orienting behavior.
AB  - The effect of hearing protection devices (HPDs) on sound localization was
      examined in the context of an auditory-cued visual search task. Participants were
      required to locate and identify a visual target in a field of 5, 20, or 50 visual
      distractors randomly distributed on the interior surface of a sphere. Four HPD
      conditions were examined: earplugs, earmuffs, both earplugs and earmuffs
      simultaneously (double hearing protection), and no hearing protection. In
      addition, there was a control condition in which no auditory cue was provided. A
      repeated measures analysis of variance revealed significant main effects of HPD
      for both search time and head motion data (p < .05), indicating that the degree
      to which localization is disrupted by HPDs varies with the type of device worn.
      When both earplugs and earmuffs are worn simultaneously, search times and head
      motion are more similar to those found when no auditory cue is provided than when
      either earplugs or earmuffs alone are worn, suggesting that sound localization
      cues are so severely disrupted by double hearing protection the listener can
      recover little or no information regarding the direction of sound source origin.
      Potential applications of this research include high-noise military, aerospace,
      and industrial settings in which HPDs are necessary but wearing double protection
      may compromise safety and/or performance.

PMID- 15960097
TI  - Design and evaluation of a prototype rear obstacle detection and driver warning
      system.
AB  - This study, concerned with the development of driver interface criteria for a
      rear obstacle detection system, assessed the appropriateness of alternative
      warning timing algorithms and evaluated various interface approaches for
      presenting warning information to drivers. Interface testing used a minivan and a
      passenger sedan equipped with a prototype rear obstacle detection system. Two
      different warning timing algorithms and four different interface conditions were
      examined. The appropriateness of the warning timing algorithms was tested using
      an alerted backing procedure wherein drivers backed to known obstacles and braked
      in response to the warning. A surprise event scenario was also included in order
      to examine driver reaction to the warning under unexpected conditions. Alerted
      backing results suggest that although both timing algorithms led to few target
      strikes, one algorithm led to more acceptable ratings, fewer target strikes and
      close calls, and less urgent braking. None of the interface warning conditions
      reliably induced avoidance braking under the surprise event condition. Actual or
      potential applications of this work include the appropriate design of effective
      backing warning systems.

PMID- 15960099
TI  - If you value nurses Mr Blair, pay for them.

PMID- 15960098
TI  - Is mental health nursing learning from inquiries?

PMID- 15960100
TI  - Finding your specialty.

PMID- 15960101
TI  - In the doctors' domain. Interview by Janis Smy.

PMID- 15960102
TI  - The new heatwave and extreme heat protection plan.
AB  - It is important for nurses to be aware of the health risks that occur during
      heatwaves and that they are able to swiftly take the appropriate action to
      protect people who have a high risk of heat-associated illness. The Department of
      Health has just issued new guidance on this.

PMID- 15960103
TI  - Vitiligo.

PMID- 15960104
TI  - Permethrin.

PMID- 15960105
TI  - Respirations.

PMID- 15960106
TI  - A programme of supervised practice in a primary care trust.
AB  - Many of the internationally trained nurses who want to work as registered nurses
      in the UK are required to undergo a period of supervised practice (adaptation) in
      a health setting accredited by the NMC. This article discusses how a supervised
      practice programme was set up and managed in an inner-London primary care trust
      aimed at internationally trained nurses who are already resident in the UK.

PMID- 15960107
TI  - Laboratory diagnosis and investigation of anaemia.
AB  - Anaemia is one of the most common conditions encountered in clinical practice.
      This article outlines the methods used to investigate anaemia and discusses the
      significance of laboratory diagnosis in treating this condition.

PMID- 15960108
TI  - Writing an Agenda for Change job description.

PMID- 15960111
TI  - All out assault. Interview by Annette Jeanes.

PMID- 15960112
TI  - Louise Crosby.

PMID- 15960113
TI  - The ward manager's premiere league.

PMID- 15960114
TI  - Payment by results.

PMID- 15960115
TI  - Worth the investment.

PMID- 15960116
TI  - Outside edge: the value of external consultancy.

PMID- 15960117
TI  - Nurses and health policy.

PMID- 15960118
TI  - Defining public value in provision care health.

PMID- 15960119
TI  - [Presumption diagnosis: otomycosis. A 451 patients study].
AB  - Otomycosis is a common disease. We try to analyze the causative factors for
      otomycosis in our environment. Our study includes 451 patients with a presumed
      diagnosis of otomycosis. The patients were included by ear, nose and throat
      specialist and general doctors; the diagnosis was confirmed in 24.43% and 16.16%
      respectively. The most common fungal pathogen found was Aspergillus spp. and
      Candida sp. The high frecuency of Aspergillus Niger may be because of the
      diferent ways of gathering samples. The abundance of Candida parapsilosis in the
      samples that came from general doctors may be because the inadequate treatment
      with topic antibiotics contributes fungal proliferation. We conclude that the
      causative factors for otomycosis could be avoided or treated. Treatment with
      antifungal agents is not enought to ensure complete cure, an furthermore the
      treatment should be aimed to restore the physiology of the external auditory
      cannal.

PMID- 15960120
TI  - [Hearing level and intensive use of mobile phones].
AB  - INTRODUCTION: Wide studies and substantial controversies build on utilization of
      actual mobile phones and appearance of systemic disorders or even tumours, but
      there is no knowledge about an eventual involvement on early hearing loss.
      PATIENTS AND METHODS: In a group of three hundred and twenty-three healthy and
      normoacoustic volunteers who were usual costumers of mobile phones an audiometric
      evaluation was made at the beginnig of its use and three years later, inquiring
      about the periods of time per day and year employed on direct contacts with
      phone. A healthy and normoacoustic control group of non users was studied too.
      RESULTS: Cases carried out 24.3 +/- 8.2 active contacts, reaching 50.4 +/- 27.8
      days of mobile phone employment in three years. Audiometric curve was similar in
      cases and controls at the beginning of the study. After this follow-up, cases
      showed an increase on hearing threshold between 1 and 5 dB HL more than controls
      in speech tones (p<0.001). Moreover, there was a trend to correlate time of phone
      use to hearing impairment, but this finding did not result statistically
      significative. CONCLUSIONS: Frequent management of mobile phones in a middle
      period of time allows to detect a mild hearing loss, but the cause of this
      disorder keeps unclear.

PMID- 15960121
TI  - [Quality of life in cochlear implanted patients].
AB  - Several articles show the audiologic benefits of cochlear implants, although it
      is still necessary to prove their impact on quality of life. In this study, 36
      Med-El processor users were included. The Glasgow Benefit Inventory (GBI) was
      used to measure changes in quality of life, and another questionnaire was used to
      evaluate the communication abilities. Eighty-six percent of the patients answered
      our questionnaire. The quality of life improved significantly according to the
      specific questionnaire. The average total benefit obtained with the GBI was +41,
      and the average scores related to general, social and physics benefits were +57,
      +16, and +3, respectively. No significant difference was found between quality of
      life and other parameters like insertion depth of the array, etiology or duration
      of the deafness.

PMID- 15960122
TI  - [Considerations about ENT emergencies. Analysis of 30000 patients assisted in 10
      years].
AB  - OBJECTIVE: To know those pathologies that require more frequently urgent medical
      assistance and what percentage of them could have been treated in health centers
      or outpatient clinics of our speciality. MATERIAL AND METHODS: Retrospective
      study of 30,000 patients attended in the Emergency department by our on call ENT
      specialist between 1993 and 2002. RESULTS: In general, epistaxis (12.98%), nasal
      traumas (10.26%) and external otitis (6.92%) were the clinical entities more
      common, representing the nasal and otological pathology more than 63% of the
      assisted emergencies. CONCLUSIONS: We demonstrate and emphasize an increment in
      the recent demand from patients of the emergency department. Several final
      considerations at that respect are pointed.

PMID- 15960123
TI  - [Prevalence and incidence studies of voice disorders among teaching staff of La
      Rioja, Spain. Clinical study: questionnaire, function vocal examination, acoustic
      analysis and videolaryngostroboscopy].
AB  - OBJECTIVE: The aim of this study was calculate the prevalence and incidence of
      voice disorders among teaching staff of La Rioja, Spain. DESIGN: We carried out a
      transversal study of voice disorders in teaching staff of La Rioja (a random
      sample of 931 of 3113 teachers) and a longitudinal study (we collect the new
      cases during the 3 years which lasts the study). PATIENTS: 527 teachers of random
      sample took part of study: 332 female (63%) and 195 male (37%). METHODS: All of
      teachers fill in a standard questionnaire, ENT and function vocal examination,
      videolaryngostroboscopy and acoustic analysis with MDVP. RESULTS: The prevalence
      of voice disorders among La Rioja Teachers was 57%: 20.3% for organic lesions
      [nodular lesions (14%), polyps (2%), submucous suffusions (1.4%), edema Reinke
      (1.2%) Sulcus (0.4%), scalp (0.6%), leucoplasia (0.2%) vocal cord paralysis
      (0.2%)] 8.1% for chronic laryngitis [not specific (2.8%), smoke (3.9%) gastroe
      sofageal reflux (2.5%)] and 29% for functional lesions [hyperfunctional dysphonia
      (7.5%) hypofunctional dysphonia (0.4%) vocal overefforts (18%) hyperplasia false
      cords (2.8)]. The incidence rate was 4 new cases each 1000 teachers and year.
      CONCLUSIONS: Organic lesions were more prevalent in women (25.4%) than in men
      (9.5%), but functional lesions and chronic laryngitis were more prevalent in men
      (36.5% and 13.2%) than in women (24% and 5%).

PMID- 15960124
TI  - [Cancer of the parotid gland].
AB  - OBJECTIVE: To review our experience and results in the diagnosis and treatment of
      a low incidence pathology such as the cancer of the parotid gland. METHODS: The
      study reviewed 40 patients with malignant tumors of the parotid gland treated
      between 1991 and 2002 in our hospital. It was used the staging system TNM
      (American Joint Committee on Cancer 1997). RESULTS: The most common histological
      type in our series is the squamous cell carcinoma, in general unilateral and in
      the superficial lobe. Rapid tumor enlargement, fixation to the skin, cervical
      lymphadenopathy, pain and facial palsy are malignancy clinical findings. We
      obtained a 56% 5-year global survival rate, with a 68% for stages I and II, and
      43% for stages III and IV. CONCLUSIONS: This pathology has a low incidence but
      high mortality. The staging and histological type are important prognostic
      factors. The surgery is the election treatment, associated with neck disection or
      radiotherapy.

PMID- 15960125
TI  - [Non Hodgkin's lymphoma in the ENT field].
AB  - OBJECTIVES: Non Hodgkin's lymphoma (NHL) is a frecuent tumor in the ENT field
      althougt there are not too many publications with a large number of patients.
      PATIENTS AND METHODS: We have studied 300 patiens with NHL and analysed the head
      and neck affectation, the presence in Waldeyer's ring, the first symptoms and the
      stage of the disease. RESULTS: Over 50% had head and neck manifestation. Of them,
      the most frequent one were adenopathies. In the Waldeyer's ring, the tonsil was
      the most frecuently affected structure. CONCLUSION: There is an evident
      relationship between NHL and the Oto-Rhino-laringology area and it is necessary
      consider it in the differential diagnosis of head and neck adenopathies.

PMID- 15960126
TI  - [Fibroxanthoma of the external auditory canal].
AB  - Atypical fibroxanthoma is an scarce skin tumor which usually develops in exposed
      areas of elderly persons. It is very uncommon in the external auditory canal,
      where it might be wrongly diagnosed as a sebaceous cyst or carcinoma. We report a
      case of atypical fibroxanthoma of the external auditory canal and review the
      current procedure for the differential diagnosis of these lesions.

PMID- 15960127
TI  - [Base tongue actinomycosis].
AB  - Actinomycosis is a bacterial, suppurative chronic infectious disease caused by
      Actinomyces israelii. Actinomycosis of the tongue is an uncommon form, and only
      3% affect the base of the tongue. We report a case with dysphagia from an
      epiglottis, vallecula and tongue base mass. Diagnosis was made on histologic
      examination of a tissue biopsy. The disease completely resolved after chirurgical
      incision and drainage of the abscess and one month of oral amoxicillin therapy.
      The recurrence of the disease, five years later, made necessary a second surgical
      procedure and one year of penicillin therapy. We comment the possible causes of
      this recurrence.

PMID- 15960128
TI  - [Radiotherapy of the neck as a risk factor for stroke].
AB  - A man (78 years) and a woman (55 years) experienced one-sided weakness and a
      woman (61 years) had language-expression problems between 4 and 37 years after
      having received radiotherapy for carcinoma of the larynx. All three patients had
      a significant degree of stenosis of the carotid artery. In two patients
      angioplasty and stenting was carried out. It was decided not to operate or stent
      the younger woman as her right internal carotid artery was occluded. No new
      symptoms developed in any of the patients. Radiation-induced stroke is not an
      uncommon disorder after radiotherapy for a laryngeal carcinoma in the past. The
      interval between radiation treatment and occurrence of stroke varies, but after a
      follow-up period of more than 5 years the risk of stroke is significantly
      increased. In the first instance the work-up should be similar to that in stroke
      patients with classical age-related atherosclerosis. However treatment of
      symptomatic radiation-induced carotid stenosis is often a challenge due to
      fibrotic changes and alterations of the anatomical layers within the radiation
      field. Screening and modification of additional cerebrovascular risk factors is
      recommended before radiation treatment is started, in order to prevent worsening
      of atherosclerotic changes.

PMID- 15960129
TI  - [Sudden infant death syndrome: the times are changing].
AB  - Case-control studies of sudden infant death syndrome (SIDS) in the Netherlands
      have shown a number of important risk factors, including prone sleeping position,
      the use of a duvet, the use of sedating antihistamines, and bed-sharing with
      parents. After issuing preventive advice to avoid these risk factors, the SIDS
      mortality rate has decreased dramatically in the Netherlands, from 100 cases per
      100,000 live births per year in the 1980s to 10-15 cases in recent years. Recent
      cohort studies of SIDS infants suggest that new risk factors are emerging. For
      example, SIDS now occurs increasingly while the infants are in day care. Such
      associations should be examined in case-control studies before preventive advice
      can be given. The Dutch SIDS risk-factor studies are an example of how
      epidemiologic studies can have a great impact on public health.

PMID- 15960130
TI  - [The cares and anxiety of those involved in the Bijlmermeer aviation disaster did
      not diminish following the medical investigations].
AB  - On October 4, 1992 a cargo jet crashed in the Bijlmermeer district in Amsterdam,
      the Netherlands, killing 43 people and making hundreds homeless. Many years of
      confusion and prolonged media attention followed, including public debates and
      even a Parliamentary Inquiry as to the causes, exposure to various chemical,
      physical and biological risk factors, and related diseases. Two comprehensive
      large-scale medical investigations were carried out: a comparative
      epidemiological study analysing the long-term effects in involved and uninvolved
      care providers, and an individual medical examination of both residents and care
      providers with medical or psychological complaints. Later, an effects study was
      added analysing the effects of both medical investigations on the feelings of
      anxiety and the attribution of symptoms among the people involved. The
      epidemiological study revealed more physical and mental symptoms among the
      involved care providers. Blood, urine and saliva tests, however, revealed no
      differences. Although the studywas carried out with great care, the findings may
      have been biased to some extent by an evoked feeling of anxiety and by attention
      toward health problems brought about by the investigation itself. Another comment
      is the technical impossibility of stating, after so long a delay, that chemical
      exposure, e.g. to depleted uranium, could not have been a cause of adverse health
      effects. The effects study demonstrated that the medical investigations generally
      did not provide reassurance or decrease the anxiety about health problems. There
      was even a small increase in complaints. Residents with health problems that had
      been involved in the disaster still attribute their complaints to harmful
      chemical exposure.

PMID- 15960131
TI  - [Possible treatments for patients with symptomatic carotid artery stenosis].
AB  - The classical treatment for severe and symptomatic stenosis of the internal
      carotid is carotid endarterectomy. An endarterectomy within two weeks after the
      initial symptoms of a TIA or CVA decreases the chances of new ischaemic symptoms.
      However, there is now an alternative for this operation, namely the placement of
      an endovascular stent. Although this method offers some advantages, there are
      still insufficient prospective randomised trials to prove that this technique is
      just as suitable as the classical method. Various studies are now in progress to
      evaluate the short- and longterm results of endovascular treatment in comparison
      with endarterectomy. For the time being, therefore, stent placement should only
      be done in the context of clinical trials.

PMID- 15960132
TI  - [Acute respiratory tract infections and acute coronary syndromes].
AB  - Epidemiological research indicates a correlation between respiratory-tract
      infections and acute cardiovascular events. Chronic infections have been linked
      to the development of atherosclerosis. As a result of chronic infections a
      prolonged and elevated inflammatory activity arises. Inflammation and the
      associated vessel-wall damage play an important role in the pathophysiology of
      atherosclerosis. Acute infections have been linked to a transient increased risk
      of unstable angina pectoris and an acute myocardial infarct. The consequence of
      acute infections is a systemic inflammatory response which results in changes in
      the atherosclerotic plaque, thrombotic activation and a prothrombotic condition.
      The inflammatory response and prothrombotic condition reinforce each other. This
      can result in coagulation on ruptured atherosclerotic plaques and erosions in the
      vessel wall, which can give rise to the sudden constriction or blockage of
      coronary arteries.

PMID- 15960133
TI  - [Epidemiology of 25 years of crib death (sudden infant death syndrome) in the
      Netherlands; incidence of crib death and prevalence of risk factors in 1980
      2004].
AB  - OBJECTIVE: To describe the prevalence of risk factors and the incidence of cot
      death (sudden infant death syndrome; SIDS) in the Netherlands during the last 25
      years. DESIGN: Descriptive. METHOD: The incidence of cot death/SIDS in infants
      aged 7-365 days in 1980-2004 was derived from Statistics Netherlands, the Dutch
      Central Bureau of Statistics. The prevalence of risk factors for cot death/SIDS
      in the general population was derived from national surveys of baby clinics (0-9
      months; 1985-2004) and studies of cot death/SIDS victims (0-23 months; 1984-1991
      and 1996/'04). RESULTS: The prevalence of the following risk factors for cot
      death/SIDS has decreased: primary prone sleeping position (from 60% to 8%), the
      use of a duvet (from 85% to 18%), maternal smoking (from 34% to 20%), paternal
      smoking (from 48% to 32%). The prevalence of routine bed-sharing with a parent
      increased from nearly 0% to 5%. The registered incidence of cot death/SIDS per
      100,000 live births decreased from 103 in 1986 to < 15 in 2003 and 2004. The
      incidence of cot deaths/SIDS that occurred during habitual bed-sharing with a
      parent, in a playpen, in child-care settings, or in a secondary prone sleeping
      position increased. CONCLUSION: The incidence of cot death/SIDS and the
      prevalence of known risk factors for cot death/SIDS has decreased. New risk
      factors have emerged in recent years. Considering the evolving conditions of
      infant care, an ongoing study on the special features of child care and the
      factors involved in cases of cot death/SIDS is warranted. This knowledge is
      essential for periodic adaptation of the national prevention programme.

PMID- 15960134
TI  - [Sudden infant death syndrome in playpens].
AB  - OBJECTIVE: To explain the increase in the number of deaths due to sudden infant
      death syndrome (SIDS) that occurred while the infant was in a playpen or on a
      playpen mat placed outside of the pen. 13 deaths were reported in the period 1
      September 1996-31 August 2004, in contrast to 0 deaths in the years 1984/'96.
      DESIGN: Descriptive. METHOD: Data on the 13 infants that were reported to the
      National Study Group on SIDS were analysed and the presence of risk factors for
      SIDS was assessed. RESULTS: Of the 13 infants, 9 were male and 4 were female. 12
      were aged less than 12 months and 1 was aged 13 months. Known risk factors for
      SIDS were often present and frequently occurred in combinations: male sex (n =
      9), higher birth order (n = 9), age 1-8 months (n = 12), parental smoking (n =
      6), primary prone sleeping position (n = 4), secondary prone (n = 6, often the
      first time), face down (n = 9), no adult present (n = 13). CONCLUSION: There was
      no clear explanation for the observed increase in SIDS that occurred in a playpen
      or on a playpen mat placed outside of the pen.

PMID- 15960135
TI  - [Pulmonary arterial hypertension due to the use of amphetamines as drugs or
      doping].
AB  - Pulmonary arterial hypertension (PAH) was diagnosed in three patients. All three
      had a history ofamphetamine consumption. The patients were a 48-year-old male
      drug addictwho had used intravenous amphetamine for more than 20 years, a 43-year
      old man who had been administered intravenous amphetamines during a period of
      intensive cycling and a 34-year-old woman who regularly consumed amphetamine at
      dance festivals. All three patients received medicinal treatment. Amphetamines
      may lead to PAH due to the release of serotonin, which causes pulmonary
      vasoconstriction and the proliferation of smooth muscle cells. Due to the
      pathophysiology of amphetamine-induced PAH, other amphetamine derivatives such as
      methylenedioxymethamphetamine (ecstasy) and methylphenidate can be risk factors
      for PAH. These three cases show that PAH should be considered in patients who
      present with dyspnoea and a reduced exertion tolerance, and who are known to have
      a history of amphetamine use.

PMID- 15960136
TI  - [Two patients with advanced non-small cell lung cancer (stage IIIB) who still
      responded very well to combined chemotherapy and radiotherapy].
AB  - In two patients, men aged 58 and 47 years respectively, advanced non-small cell
      lung cancer (stage IIIB) with mediastinal and supraclavicular lymph-node
      metastases was diagnosed. Both patients had a good performance score despite the
      seriousness of their tumours. They were treated with chemotherapy followed by
      radiotherapy and the treatment was well tolerated. In the patient aged 47 years,
      lobectomy was performed one year later for a second primary carcinoma. Both
      patients were still disease-free 5 years after treatment. Although not every
      patient with stage IIIB lung cancer will respond so well to combined treatment,
      these cases illustrate that intensive treatment may be recommended for selected
      patients. The final therapeutic advice has to be made by a multidisciplinary
      team. If the treatment chosen includes both chemotherapy and radiotherapy then
      careful scheduling is required.

PMID- 15960137
TI  - [Terminal sedation in the Netherlands].

PMID- 15960138
TI  - [Terminal sedation in the Netherlands].

PMID- 15960139
TI  - [Terminal sedation in the Netherlands].

PMID- 15960140
TI  - [Terminal sedation in the Netherlands].

PMID- 15960141
TI  - ['Artificial support in case of hepatic failure'; a report from the Dutch Health
      Council].

PMID- 15960142
TI  - Implication of the peak serum level of mizoribine for control of the serum anti
      dsDNA antibody titer in patients with lupus nephritis.
AB  - AIM: Mizoribine (MZR) is a novel selective inhibitor of inosine monophosphatase
      dehydrogenase that was developed in Japan. We previously reported the efficacy
      and safety of oral MZR pulse therapy, which is associated with elevated peak
      serum MZR levels, in selected patients with lupus nephritis. However, only
      limited information is available as yet on the optimal peak serum level of MZR
      that would yield an enhanced clinical efficacy without serious toxicity in
      patients with lupus nephritis. METHODS: A total of 11 patients with clinically
      stable lupus nephritis treated with oral MZR pulse therapy combined with low-dose
      prednisolone were enrolled in the cross-sectional study. The peak serum
      concentrations of MZR (as determined by HPLC) and the serum anti-dsDNA antibody
      titers (as determined by ELISA) were examined in the patients in order to
      evaluate the correlation between these two parameters. The correlation between
      the dose of MZR (mg/kg) administered orally as a single daily dose and the peak
      serum level of the drug was also examined. In two of the patients, serial
      measurements of the changes in the peak serum levels of MZR and anti-dsDNA titers
      could be conducted over 10 months. RESULTS: A significant inverse correlation (r
      = -0.596, p = 0.0116) was observed between the peak serum levels of MZR and the
      serum anti-dsDNA antibody titers in the study participants, while the dose of
      prednisolone remained unchanged. The peak level of MZR in the serum was
      significantly correlated with the single dose of MZR (r = 0.509, p = 0.0371). In
      the two patients in whom serial measurements were conducted, the first patient
      who showed a peak serum MZR level of less than 2.5-3.0 microg/ml eventually
      developed an increase of the serum anti-dsDNA titer with hypocomplementemia and
      proteinuria. On the other hand, in the second patient who showed a peak serum MZR
      level in excess of 4.0 microg/ml, persistently low serum anti-dsDNA titers with
      normocomplementemia were observed. CONCLUSION: Although this study is only a
      preliminary study conducted on a small sample, we speculate from the results that
      a peak serum level of MZR of at least more than 2.5-3.0 mirog/ml is necessary to
      achieve satisfactory clinical efficacy of the drug for the treatment of lupus
      nephritis. Further study is needed to confirm these preliminary findings.

PMID- 15960143
TI  - Antineutrophil cytoplasmic antibodies (ANCA) in Chinese patients with anti-GBM
      crescentic glomerulonephritis.
AB  - OBJECTIVE: To study the prevalence of ANCA and their target antigen in Chinese
      patients with anti-GBM crescentic glomerulonephritis (CGN), and to evaluate the
      possible role of ANCA in Chinese anti-GBM CGN patients with coexisting serum ANCA
      by studying clinicopathologic features of this disease. MATERIAL AND METHODS:
      Twenty-three sera were collected from 23 renal biopsy-proven anti-GBM CGN
      patients. According to the standardized procedures, all of the sera were
      determined by both, indirect immunofluorescence (IIF) ANCA, and enzyme-linked
      immunosorbent assay (ELISA) MPO-ANCA, PR3-ANCA and BPI-ANCA. The patients were
      divided into two groups according to serum ANCA positivity (Group A) or
      negativity (Group B). Thirty-three ANCA-associated pauci-immune CGN patients were
      regarded as control group (Group C). Their clinicopathologic features were
      compared to reveal whether ANCA correlated with disease activity. RESULTS: There
      were 11 (47.8%) cases with positive serum ANCA in 23 anti-GBM glomerulonephritis
      patients. There were 4/11 MPO-ANCA (one with positive PR3-ANCA and C-ANCA, three
      with negative IIF-ANCA), 1/11 PR3-ANCA (with positive MPO-ANCA and C-ANCA), 3/11
      P-ANCA (with negative ELISA-ANCA) and 5/11 C-ANCA (one with positive PR3-ANCA and
      MPO-ANCA, and the other four with negative ELISA-ANCA). No BPI-ANCA was detected.
      No different clinicopathologic features were found between Groups A and B. Both
      were different from Group C in age, sex ratio, frequence of anuria and ESRD,
      variety of crescents, glomerular sclerosis, vessel lesion and prognosis.
      CONCLUSION: Our data demonstrate that ANCA in Chinese patients with anti-GBM CGN
      is not rare. The major target antigen of ANCA is MPO. ANCA seems not to be
      correlated with disease activity.

PMID- 15960144
TI  - Lower serum magnesium levels are associated with more rapid decline of renal
      function in patients with diabetes mellitus type 2.
AB  - AIMS: Hypomagnesemia has been implicated in adversely affecting diabetic
      complications. This is a retrospective study designed to determine whether there
      is any association between serum magnesium concentration [Mg2+] and the rate of
      renal function deterioration, as determined by the slope of serum creatinine
      reciprocals versus time (1/SCr-vs-t), in patients with diabetes mellitus type 2
      (DM2). MATERIALS AND METHODS: DM2 patients without known kidney disease seen at
      Olive View-UCLA Medical Center for any reason during January-March 2001 were
      included. For each patient, all available data from our electronic database for
      [Mg2+], hemoglobin A(1C) (HbA(1C), serum creatinine (SCr), lipid profiles,
      routine urinary analysis, as well as history of hypertension and pharmacy
      profiles were retrieved. The average of all parameters obtained and linear
      regression analyses for the slope of 1/SCr-vs-t plot were performed for each
      patient. Patients were stratified by gender and divided into four groups based on
      increasing [Mg2+]. Correlations between each parameter including the slope of
      1/SCr-vs-t and the four magnesium groups were analyzed. RESULTS: 252 males and
      298 females with a mean follow-up of 62.6 +/- 22.5 months were included. Patients
      belonging to lower [Mg2+] groups for both genders had significantly worse slopes
      of 1/SCr-vs-t plot independent of the presence of hypertension and use of
      ACEI/ARB, diuretics, HMG-CoA enzyme inhibitors or aspirin. In a multivariate
      regression analysis controlling for age, HbA(1C) and various components of the
      lipid profile, [Mg2+] remained an independent predictor for the slope of 1/SCr-vs
      t. A trend for worse proteinuria based on routine urinary analysis was observed
      among patients belonging to the lowest [Mg2+] group. CONCLUSIONS: Lower [Mg2+] is
      associated with a faster renal function deterioration rate in DM2 patients.

PMID- 15960145
TI  - Epitope analysis of myeloperoxidase-specific antineutrophil cytoplasmic
      autoantibodies (MPO-ANCA) in childhood onset Graves' disease treated with
      propylthiouracil.
AB  - AIM: This study aimed to elucidate the relationship between epitope profiles and
      clinical manifestations of patients with myeloperoxidase antineutrophil
      cytoplasmic autoantibodies-(MPO-ANCA) positive childhood onset Graves' disease
      treated with propylthiouracil (PTU). METHODS: Sixteen patients were studied. The
      patients were grouped into ten without clinical vasculitis and nephritis (non
      vasculitis group) and six with biopsy-proven pauci-immune necrotizing crescentic
      glomerulonephritis (vasculitis group). Epitope analysis was performed on serum
      samples by an enzyme-linked immunosorbent assay (ELISA) using a panel of
      recombinant deletion mutants of MPO. RESULTS: The high frequency sites were
      region upstream of Met341 (Ha region) near the N-terminus of the heavy chain, and
      regions downstream of Gly598 (Hf and Hg regions) near the C-terminus. Most
      patients in the non-vasculitis group had polyclonal MPO-ANCA recognizing both the
      above linear sites and other epitope sites of the heavy chain of MPO. Only one of
      ten patients in the non-vasculitis group, and four of six patients in the
      vasculitis group had MPO-ANCA recognizing only the linear sites of the heavy
      chain of the MPO molecule (Ha, Hf and/or Hg). Of the four patients in the
      vasculitis group, two had nephritis, like rapidly progressive glomerulonephritis
      and one had alveolar hemorrhage. CONCLUSION: These findings suggest that most
      patients with childhood onset Graves' disease treated with PTU who manifest no
      vasculitis have polyclonal MPO-ANCA recognizing both the linear and other epitope
      sites of the heavy chain of MPO. However, some patients who develop nephritis
      have MPO-ANCA recognizing only the linear sites of the heavy chain of MPO. This
      clonality of MPO-ANCA may be a risk factor that induces clinical vasculitis and
      nephritis in patients treated with PTU. Therefore, patients exposed to PTU should
      be monitored for MPO-ANCA level and epitopes.

PMID- 15960146
TI  - Influence of carvedilol on chronic renal failure progression in spontaneously
      hypertensive rats with adriamycin nephropathy.
AB  - BACKGROUND: In this study, the effects of carvedilol, antihypertensive (alpha
      beta blocker) agent with antiproliferative and antioxidative properties, on
      slowing down of chronic renal failure (CRF) progression in spontaneously
      hypertensive rats (SHR) with adriamycin (ADR) nephropathy were examined. METHODS:
      Eighty adult (24 weeks) SHR were divided into four groups: CONTROL GROUP: 20 SHR;
      ADR group: 20 SHR treated with ADR (2 mg/kg i.v. twice in 20 days); ADR-C group:
      20 SHR treated with ADR and with carvedilol (30 mg/kg/day); ADR-CC group: 20 SHR
      treated with carvedilol and captopril (60 mg/kg/day). Systolic blood pressure was
      measured every two weeks, renal blood flow (RBF), mean arterial pressure (MAP)
      and renal vascular resistance (RVR) were determined at Weeks 6 and 12, creatinine
      clearance and proteinuria at Weeks -3 (see measurements), 6 and 12. The rats were
      sacrificed at Weeks 6 and 12 after the second ADR injection. Glomerular
      sclerosis, tubulointerstitial and blood vessel changes were determined by
      semiquantitative scoring. RESULTS: Carvedilol decreased systolic blood pressure.
      It decreased RVR and MAP, and increased RBF significantly. Carvedilol also
      significantly decreased interstitial infiltration in the early phase of the
      study, slowed down the development of interstitial fibrosis and tubular atrophy
      and decreased blood vessel changes. The hemodynamic and morphological effects of
      carvedilol were associated with slowing down the CRF progression as well as a
      mild decrease in proteinuria. Captopril addition to carvedilol improved its
      effects especially on prevention of tubulointerstitial changes. CONCLUSIONS:
      Results of this experimental study showed beneficial effect of carvedilol and its
      combination with captopril on CRF progression, indicating that clinical studies
      are warranted.

PMID- 15960147
TI  - Once-weekly intravenous paricalcitol in the treatment of secondary
      hyperparathyroidism in hemodialysis patients.
AB  - BACKGROUND: Paricalcitol, a vitamin D analog, is commonly administered three
      times weekly to control secondary hyperparathyroidism in hemodialysis patients.
      Less frequent dosing would be more convenient, require less nursing time, and be
      an option in other dialysis modalities. No studies have examined the efficacy of
      once-weekly dosing of paricalcitol. METHODS: Chronic hemodialysis patients
      receiving a stable dose of paricalcitol three times weekly with intact PTH (iPTH)
      100-500 ng/l were monitored during a two-week baseline, then were converted to a
      single mid-week paricalcitol dose equal to the previous cumulative weekly dose.
      Serum calcium and phosphorus were monitored weekly and iPTH levels determined
      during study Weeks 4 and 8. A single paricalcitol dose adjustment was made during
      study Week 5 based on iPTH to achieve a target value of 150-300 ng/l. Phosphate
      binders and calcium dialysate bath were kept constant during the study. RESULTS:
      In the 25 patients, mean iPTH was 295 +/- 107 ng/l at baseline, and not
      significantly different at Week 4 (307 +/- 111 ng/l) or Week 8 (285 +/- 98 ng/l).
      Paricalcitol dose increases mid-study were almost exclusively in patients with
      iPTH > 300 ng/l. Calcium, phosphorus, and calcium x phosphorus product were not
      significantly different on weekly therapy. (Only one patient developed a calcium
      > 2.55 mmol/l during the study.) CONCLUSION: Once-weekly dosing of paricalcitol
      is an effective option in treatment of secondary hyperparathyroidism. Less
      frequent dosing may better allocate nursing time and potentially benefit other
      patient populations with CKD and ESRD.

PMID- 15960148
TI  - Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of
      hyperphosphatemic patients with end-stage renal disease.
AB  - AIMS: High serum phosphorus levels are a common problem in patients receiving
      long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non
      aluminum, non-calcium phosphate binder developed for the treatment of
      hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data
      from a recent trial, which, for the first time, assessed the efficacy and
      tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese
      patients with ESRD. PATIENTS AND METHODS: Following a one- to three-week washout
      phase and a four-week, open-label lanthanum carbonate dose-titration phase, male
      and female hemodialysis patients were randomized (1:1) to receive either
      lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of
      the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or =
      5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during
      titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P)
      product levels. The safety and tolerability of lanthanum carbonate were assessed
      by monitoring adverse events throughout the study. RESULTS: Mean serum phosphorus
      level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and
      there was no evidence of a difference in levels between the treatment groups pre
      randomization. At the end of the study, lanthanum carbonate-treated patients had
      significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl];
      n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31;
      p < 0.001). In addition, a significantly higher proportion of patients receiving
      lanthanum carbonate had controlled serum phosphorus levels (60%) compared with
      the placebo group (10%; p < 0.001). Ca x P product levels were also significantly
      lower in the lanthanum carbonate group at the end of randomized treatment (p <
      0.001). Lanthanum carbonate was well tolerated; only one serious adverse event
      was reported, which was unrelated to treatment. CONCLUSIONS: Lanthanum carbonate
      was shown to be an effective and well-tolerated phosphate binder for the
      treatment of hyperphosphatemia in Chinese patients with ESRD. This finding
      supports the results of previous US and European studies, which have also shown
      that lanthanum carbonate treatment effectively controls serum phosphorus levels.

PMID- 15960149
TI  - Kidney disease associated with primary antiphospholipid syndrome: clinical signs
      and histopathological features in an case experience of five cases.
AB  - BACKGROUND: The primary antiphospholipid syndrome (PAPS) is characterized by the
      presence of circulating antiphospholipid antibodies, clinically associated with
      blood hypercoagulability. Renal involvement in course of PAPS is very frequent,
      although the true prevalence of PAPS-correlated kidney disease is difficult to
      estimate. MATERIALS AND METHODS: We reviewed 270 consecutive renal biopsies
      examined in our Nephrology Division of Bari University Hospital between 1998 and
      2004 to identify those performed in patients with PAPS. RESULTS: We identified
      five biopsies performed in patients with PAPS. In three patients the diagnosis of
      PAPS was made at onset of the kidney disorder, while in the other two cases the
      initial diagnosis was primary focal segmental glomerulosclerosis (FSGS). In these
      cases the subsequent finding of positive antiphospholipid antibodies reoriented
      the diagnosis toward PAPS-correlated nephropathy. The clinical onset of kidney
      disease consisted of acute renal failure in three patients and urinary
      abnormalities in the other two. Histological examination of renal biopsies showed
      vascular lesions (intimal fibrous hyperplasia, arteriolar hyalinosis, double
      outline of the capillary walls) in four patients. Focal segmental
      glomerulosclerosis was present in four patients, two of whom showed double
      outline of the capillary walls. All patients had tubulo-interstitial lesions,
      while immunofluorescence was positive in only two patients. All patients
      preserved stable renal function throughout follow-up (mean value: 10.6 years,
      range 4 months-24 years). The prevalence of PAPS-correlated nephropathy in our
      population was 1.85% CONCLUSION: Our data confirm that PAPS-associated
      nephropathy has slow progression and rarely leads to end-stage renal failure. The
      prevalence of PAPS-correlated nephropathy is likely underestimated because some
      patients with a diagnosis of primary focal sclerosis may actually be affected by
      PAPS.

PMID- 15960150
TI  - Poststreptococcal acute glomerulonephritis superimposed on bilateral renal
      hypoplasia.
AB  - An 8-year-old girl with preexisting chronic renal failure (CRF) due to bilateral
      renal hypoplasia presented with edema, gross hematuria and acute deterioration of
      renal function. The diagnosis of poststreptococcal acute glomerulonephritis
      (PSAGN) was made based on clinical presentation, red blood cell casts, low level
      of C3 and elevated antistreptolysin 0 titer. Her course was prolonged with serum
      creatinine increased from the baseline level of 1.1 mg/dl to 2.2 mg/dl, returning
      toward the baseline level (1.2 mg/dl) after one month. Serum creatinine then
      started to increase again. The slope of creatinine clearance over time became
      steeper after the episode of PSAGN. A severe course of PSAGN and subsequent
      deterioration of renal function have previously been reported in patients with
      diabetic nephropathy or focal glomerulosclerosis. The present case along with a
      literature review suggests that individuals with fewer nephrons are at higher
      risk of severe course and outcome of PSAGN. Conversely, patients with severe
      PSAGN may be born with fewer nephrons due to low birth weight, unrecognized renal
      hypoplasia or other unknown causes.

PMID- 15960152
TI  - Critical renal artery stenoses may cause a spectrum of cardiorenal failure and
      associated thromboembolic events.
AB  - A wide spectrum of acute or chronic heart failure and thromboembolic events may
      be causally related to high-grade uni- or bilateral renovascular hypertensive
      disease, and the variety of these potential interactions may be unrecognized in
      clinical practice. We present three cases that illustrate the clinical
      variability of cardiorenal failure and thromboembolic events seen in patients
      with significant renal artery stenoses. These are high-risk patients where severe
      morbidity and mortality are threatening. Our patients also demonstrate that the
      diagnosis often is delayed, and that recanalizing of occluded renal arteries may
      be highly cost-effective and life-saving in such patients.

PMID- 15960151
TI  - A case of gain-of-function mutation in calcium-sensing receptor: supplemental
      hydration is required for renal protection.
AB  - AIMS: The calcium-sensing receptor (CaSR) regulates the extracellular calcium
      level, mainly by controlling parathyroid hormon secretion and renal calcium
      reabsorption. In gain-of-function CaSR mutations, the genetic abnormalities
      increase CaSR activity leading to the development of such clinical manifestations
      as hypercalciuric hypocalcemia and hypoparathyroidism. We report a Japanese case
      of CaSR gain-of-function mutation and represent a therapeutic intervention based
      on the functional characteristics of CaSR in renal tubule. METHODS AND RESULTS
      (CASE): DNA sequence analysis revealed a heterozygous G to T mutation identified
      in a 12-year-old Japanese girl presenting with sporadic onset of hypercalciuric
      hypocalcemia and hypoparathyroidism. The mutation is located in the N-terminal
      extracellular domain of the CaSR gene, one of the most important parts for the
      three-dimensional construction of the receptor, resulting in the substitution of
      phenylalanine for cysteine at amino acid 131 (C131F) in exon 3. Based on the
      diagnosis of the gain-of-function mutation in the CaSR, oral hydrochlorothiazide
      administration and supplemental hydration were started in addition to calcium
      supplementation. The combination therapy of thiazide and supplemental hydration
      markedly reduced both renal calcium excretion and urinary calcium concentration
      from 0.4-0.7 to less than 0.1 mg/mg (urinary calcium/creatinine ratio) and from
      10-15 to 3-5 mg/dl (urinary calcium concentration), respectively. This therapy
      stopped the progression of renal calcification during the follow-up period.
      CONCLUSION: Supplemental hydration should be considered essential for the
      following reasons: (1) calcium supplementation activates the CaSR in the kidney
      and suppresses renal urinary concentrating ability, (2) the thiazide has a
      diuretic effect, (3) as calcium supplementation increases renal calcium
      excretion, the supplemental hydration decreases urinary calcium concentration by
      increasing urinary volume, thereby diminishing the risk of intratubular
      crystallization of calcium ion.

PMID- 15960153
TI  - Obstructive icterus directly related to visceral artery aneurysm in a CAPD
      patient.
AB  - Visceral artery aneurysms (VAA) are uncommon pathologies. We report a case of the
      first CAPD patient with obstructive jaundice directly related to VAA. A 25-year
      old man with a four-year history of hemodialysis followed by two years of CAPD
      was admitted due to jaundice. He had two episodes of peritonitis. An abdominal
      ultrasonogram and a selective common hepatic arteriogram confirmed the presence
      of a 5 cm saccular aneurysm supplied from the gastroduodenal artery and a 4 cm
      fusiform aneurysm supplied from the proximal part of the common hepatic artery.
      The gastroduodenal artery was responsible for the impression of the common bile
      duct. In the operation, the gastroduodenal artery aneurysm was completely excised
      after its proximal and distal ends were ligated. The proximal and distal ends of
      the hepatic artery were also ligated. A prosthetic graft (PTFE), which extended
      from the splenic artery to the distal portion of the hepatic artery, was placed.
      In this way, the arterial blood flow of the liver was re-established. Patients
      with VAAs present with a constellation of symptoms including abdominal pain,
      jaundice and shock (due to rupture of aneurysm). Pancreatitis, and
      atherosclerosis have been reported to be the most common causes of VAAs. In
      conclusion, when CAPD patients present with jaundice or hemorrhagic shock with
      abdominal pain, VAA should be considered in differential diagnosis, especially if
      patients have a history of frequent pancreatitis episodes, and severe risk
      factors for atherosclerosis.

PMID- 15960154
TI  - Cirrhosis and IgA nephropathy related to the PiSZ phenotype of alpha1-antitrypsin
      deficiency.

PMID- 15960155
TI  - Successful pregnancy complicated by microscopic polyarteritis nodosa.

PMID- 15960156
TI  - Immunoglobulin A nephropathy associated with cyclic neutropenia.

PMID- 15960157
TI  - The effect of surface pore size on the differentiation of rat bone marrow cells:
      morphological observations and expression of bone related protein mRNA.
AB  - The purpose of this study was to investigate the behavior of rat bone marrow
      cells (RBM) growing on surfaces with different pore sizes. RBM behavior on
      Millipore filters (MF-Millipore membrane filter) made from cellulose mixed esters
      with 5 different pore surfaces (0.45 microm, 1.2 microm, 3.0 microm, 5.0 microm
      and 8.0 microm) were compared in terms of morphological changes on the different
      pore sizes. Furthermore, the expressions of osteopontin and osteocalcin mRNAs
      were investigated. On the 1.2 microm and 3.0 microm pore surfaces, RBM attached
      to the substrate well, but cells on the 5.0 microm and 8.0 microm pore surfaces
      invaded deeply into the pores. Higher levels of both osteopontin and osteocalcin
      mRNA expression were always observed in cells cultured on the 1.2 microm filter.
      These results suggest that the 1.2 microm Millipore filter pore size is the most
      suitable for inducing RBM to differentiate into an osteoblastic phenotype among
      these surfaces and is probably related to production of the ECM but not to the
      phenomenon of cell spreading.

PMID- 15960158
TI  - The influence of prosthesis designs and loading conditions on the stress
      distribution of tooth-implant supported prostheses.
AB  - The aim of this study was to observe the influence of prosthesis design and
      loading condition on the stress distributions of tooth-implant supported
      prostheses. Six 2D finite element models, two reference models, and four
      experimental models were computed to simulate different prosthesis designs. Six
      different loading conditions were applied to investigate the stress distributions
      of tooth and implant, respectively. The stresses of reference models were
      considered as 100%; the stresses of experimental models at the same locations
      were compared with those of reference models. The stresses around implants were
      higher than those around teeth. When vertical loading was applied only on the
      implant, the stresses to both the implant and teeth were at their lowest. The
      highest stress to the tooth was in the model TTPF and the lowest in the model
      TPFF. The highest stress to the implant was in the model TPPF and the lowest in
      the model TPFF. These data indicated that the loading on the tooth-implant
      supported prosthesis was mainly supported by the implant. Minimizing the loading
      on the tooth decreased the stress to both the tooth and the implant. Adding
      fixtures as abutment was more effective in decreasing the stress than adding
      tooth as abutment in tooth-implant supported prosthesis.

PMID- 15960159
TI  - Adenomatoid odontogenic tumor arising from the mandibular molar region: a case
      report and review of the literature.
AB  - This case report describes a rare case of an adenomatoid odontogenic tumor (AOT)
      arising in the mandibular third molar region of a 20-year-old female. The tumor
      was a well-circumscribed intraosseous lesion with an embedded tooth.
      Histologically, the induction of extensive globular calcification was evident in
      addition to the characteristic histological features of AOT. The present case
      lends support to the categorization of AOT as an odontogenic tumor consisting of
      a disorderly mixture of odontogenic epithelium and odontogenic ectomesenchyme
      with calcification.

PMID- 15960160
TI  - Canalicular adenoma arising in the upper lip: review of the pathological
      findings.
AB  - This case report describes a rare case of canalicular adenoma arising in the
      upper lip of a 61-year-old male patient. Macroscopic examination of the tumor
      revealed a well-defined, smooth, firm, elastic hard, round nodule with a diameter
      of 1.0 cm. The cut surface was white. Histopathology showed that the tumor was an
      encapsulated mass with a complex cellular pattern of anastomosing duct-like or
      trabecular structures lined by a single layer of tall columnar epithelial cells,
      which were embedded in a loose, fibrous, and highly vascular connective tissue
      stroma. The tumor cells were immunoreactive to AE1/AE3, CK19 and S-100, were
      partially positive for CK7, CK8, GFAP and PCNA, but were negative for SMA, CK13,
      CK14 and vimentin.

PMID- 15960161
TI  - [Tongue diagnosis support system].
AB  - Tongue diagnosis is one of the most important diagnostic methods in Oriental
      Medical Science (OMS). This diagnosis is painless and non-invasive method.
      However, it is not easy to cultivate skillful doctors. As one of the reasons,
      definition of tongue color is rather subjective and sensuous measure and color
      isn't related to quantitative physical value. It is, therefore, necessary to
      associate tongue color with physical numerical value. There are two problems to
      overcome the issue. 1) It is necessary for diagnosis to extract a region for
      diagnosis from entire picture because a tongue picture consists of two regions, a
      tongue and a background. 2) Associate tongue color with physical numerical value.
      For extracting tongue region, we used Progressive LiveWire method that is an
      Active Contour Model. And, for associating tongue color with physical
      measurement, we propose a hierarchical method. We use static rule and support
      vector machine for clustering colors. The performance of developed system is
      improved compared with an early developed one. In addition, the developed system
      did not make a critical incorrect discernment that causes incorrect choice about
      inspection in the layer of rule base. In this research average color appraisal is
      done from the region of 37 points. But, color judgment in the literature with the
      judgment by the eye of the human, has always done average judgment with not to
      limit, there is also a possibility some weight attaching being done. Therefore,
      from either one enabling the mass data and the comparison with the group of
      specialists is necessary as an appraisal.

PMID- 15960162
TI  - [Evaluation of MRI finding and histopathological changes in the rabbit kidney
      following transcutaneous cryogenic surgery].

PMID- 15960163
TI  - [Study on the effects of irradiation around the cervical stellate ganglion].

PMID- 15960164
TI  - [New characterization of the stereoscopic structure of proteins by using expanded
      Gauss mapping and total curvature].

PMID- 15960165
TI  - [Evaluation of the capacity to detect F-18-FDG-PET in stomach cancer].

PMID- 15960166
TI  - [Histological changes in a normal rabbit kidney following transcutaneous
      cryogenic surgery--on the development of apoptosis].

PMID- 15960167
TI  - [Molecular pathological analysis of polypoid border lesion of the colon that has
      been endoscopically excised].

PMID- 15960168
TI  - [Explanation of the action of immunoglobulins in preventing spontaneous abortion
      in an immunologically sterile mouse model].

PMID- 15960169
TI  - [Successful balloon-occluded retrograde transvenous obliteration (B-RTO) in a
      case of symptomatic epilepsy with hepatic encephalopathy due to non-cirrhotic
      porto-systemic shunt].
AB  - We report a 66-year-old man with hepatic encephalopathy due to a non-cirrhotic
      porto-systemic shunt during the course of treatment for epilepsy with sodium
      valproate. The patient developed symptomatic epilepsy after an operation for
      intracranial arterio-venous malformation at the age of 41, and had been treated
      with sodium valproate and phenytoin since. At the age of 66, he developed
      convulsions that were thought to be symptomatic epilepsy with hyperammonemia.
      Despite sodium valproate having been tapered rapidly and then discontinued,
      hyperammonemia continued. Abdominal contrast enhanced CT demonstrated a large
      spleno-renal shunt. Although he was treated with lactulose, he developed
      encephalopathy with hyperammonemia several times. At the age of 67, we occluded
      the spleno-renal shunt by balloon-occluded retrograde transvenous obliteration (B
      RTO), after which, his clinical symptoms improved, together with normalizing of
      the ammonia level and EEGs.

PMID- 15960170
TI  - [A case of brachial amyotrophic diplegia accompanied with Sjogren's syndrome
      presenting good response to immunotherapies in the early course of the disease].
AB  - A 74-year-old woman suffered from progressive muscle atrophy and weakness of her
      arms since she was seventy two years old. Before referral to our department, she
      was diagnosed as having cervical spondylotic myeloradiculopathy and received
      spinal fusion. Though spinal decompression was successful, muscle weakness of her
      upper limbs were progressive even after the surgery. On admission, neurological
      examinations revealed marked atrophy and weakness of her bilateral upper limbs
      with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower
      extremities had normal muscle strength, but fasciculations were seen in her all
      four limbs. Electrophysiologically, motor nerve conduction velocity was almost
      normal but the amplitude was remarkably decreased, conduction block was not
      detected, and electromyography showed neurogenic patterns on her all extremities.
      Spinal progressive musclar atrophy (SPMA) accompanied with Sjogren's syndrome was
      the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her
      serum, we assumed that anterior horn cells were impaired by an autoimmune
      mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange
      (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid
      pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable
      improvement on her weakness, and the effect lasted for about three months. This
      is the first case of SPMA with Sjogren's syndrome which showed good response to
      PE and IVIG in the early course of the disease. We considered that some SPMA-like
      motor neuron syndrome accompanied with autoimmune features may require
      immunomodulating therapies.

PMID- 15960171
TI  - [A case of primary progressive multiple sclerosis with onset of memory
      impairment].
AB  - We report a 52-year-old woman with primary progressive multiple sclerosis (PPMS)
      presenting with chronic progressive memory impairment. From a couple of years
      prior to admission, she had developed impairment of her short-term memory. For
      example, she forgot her nephew's name, and spoke the same phrases again and
      again. She also sometimes forgot to turn off her gas stove and forgot things she
      bought in shops. Moreover, her mental activity gradually decreased and she became
      apathetic. However, she did not note her memory impairment, and had no
      hallucinations. She was admitted to our hospital on 20 May, 2003 because
      donepezil had been ineffective for treating her memory impairment.
      Neurologically, she showed bilateral horizontal gaze nystagmus, mild limb ataxia
      on the left and mildly ataxic gait. Neuropsychological examinations showed mildly
      impaired cognitive function, e.g., MMSE 25/30, WAIS-R full IQ 69 and especially
      in verbal short memory, which may represent temporal lobe dysfunction. Moreover,
      Benton's visual memory test revealed marked visual short-term memory impairment,
      while impaired performance on a Kana picking up test suggested mild to moderate
      attention impairment, which could have represented frontal lobe dysfunction.
      Brain MRI showed multiple T2-high plaque lesions close to the bilateral lateral
      ventricles, and bilateral optic nerve lesions enhanced by gadolinium. Also,
      spinal cord MRI showed a gadolinium enhanced lesion at Th5 on the left. Cerebral
      spinal fluid (CSF) examination showed normal cell count and protein level, and
      undetectable oligoclonal bands (OCB), but an elevated IgG index (1.1, normal <
      0.85). Visual evoked potentials (VEPs) showed prolonged P100 latency bilaterally,
      indicating subclinical optic nerve lesions. She was thus diagnosed as having PPMS
      according to McDonald's diagnostic criteria for MS. 99mTc Single photon emission
      computed tomography (SPECT) showed a decreased cerebral blood flow (CBF) in the
      bilateral frontal and temporal lobes, which was consistent with her clinical
      features. PPMS patients generally present with chronic progressive spastic
      paraparesis and/or cerebellar ataxia. Cognitive impairments observed in PPMS are
      generally thought to be due to white matter lesions, i.e., subcortical dementia.
      However, some recent reports have shown MS patients with short-term memory
      impairment (antegrade amnesia) similar to cortical dementias such as Alzheimer's
      disease (AD). In such MS cases, visual short-term memory impairment seems
      characteristic of their cognitive impairment compared to AD cases. As well, the
      present case showed visual memory impairment as evaluated by Benton's memory
      test. Parietal and frontal lobes are reported to be important for verbal and
      visual working memory, respectively. Thus, in the present case, decreased CBF in
      the frontal and temporal lobes, which could have been due to a disconnection
      between cortices and subcortices caused by the white matter lesions, is
      consistent with the type of her cognitive dysfunction, i.e., notable visual
      memory impairment. PPMS may thus be an important disease as a differential
      diagnosis for chronic progressive dementia. Further neuropsychological and
      functional imaging studies will be necessary to achieve a better understanding of
      the mechanisms of cognitive impairment in PPMS.

PMID- 15960172
TI  - [A case of Brown-Vialetto-van Laere (BVVL) syndrome in Japan].
AB  - Here we report a sixty-year-old woman of Brown-Vialetto-van Laere (BVVL) syndrome
      in Japan. She had sensorineural deafness, weakness and atrophy of her extremities
      from 15 years of age. Her neurological symptoms slowly progressed. She first
      visited our hospital in 1993 when she was 49 years old. At that time, she had
      distal muscle weakness and atrophy of the four extremities and bulbar palsy. Deep
      tendon reflexes were absent and the plantar toe reflex was flexor. EMG revealed
      neurogenic changes and the nerve conduction studied were normal. The vital
      capacity was marked decreased. On August 10, 2003, she was admitted to our
      hospital because of CO2 narcosis. She had III, VII, X, XI, XII cranial nerve
      palsy, distal muscle weakness and atrophy of the four extremities. From her
      neurological symptoms and signs, we made a diagnosis of BVVL syndrome. MRI
      revealed no high signal in pyramidal tract by FLAIR image. ABR showed no
      response, and VEP demonstrated delay of the P100. She was intubated, and was
      attached to a respirator to improve her CO2 narcosis. After treatment she
      improved and did not need to be assisted by a respirator during daytime. During
      night time, she had apnea, and her blood gas showed the retention of CO2, and she
      still required the respiratory assistance during her sleep. This is the first
      report of BVVL syndrome in Japanese literature.

PMID- 15960173
TI  - [An autopsied case of medullary glioma with an abrupt onset of headache and
      hemiparesis].
AB  - We describe an 89-year-old woman who presented with an abrupt onset of headache
      and right hemiparesis. With the initial diagnosis of cerebral infarction, we
      started therapy using sodium ozagrel. The right hemiparesis worsened, however,
      and a continuous intravenous heparin injection showed no effect. Furthermore,
      nystagmus in the bilateral eyes, dysphagia, left hemiparesis, and central
      ventilation disorder appeared one after another in three weeks. A magnetic
      resonance images (MRI) of the head, performed on the fifth hospital day with
      regular intervals of axial sections, disclosed no lesion responsible for right
      hemiparesis. MRI of the brainstem and upper cervical cord, performed after two
      weeks with smaller intervals of axial sections, revealed a T2 high signal lesion
      in the left side of the medulla oblongata and upper cervical cord. After about
      five weeks from the onset of the disease, she died of pneumonia. With the
      pathological examination, we diagnosed as glioma originated in the left ventral
      part of medulla oblongata. Five similar cases of brainstem glioma have been
      reported so far. Our patient, the oldest one, showed an exceptionally rapid
      clinical course, instructing us to consider the possibility of medullary glioma
      even in the elderly patients presenting with acute onset hemiparesis followed by
      rapid and progressive appearance of brainstem signs.

PMID- 15960174
TI  - [Herpes simplex encephalitis originating from bilateral thalamic lesions with
      hemorrhagic component].
AB  - A 71-year-old woman with hypertension and hypothyroidism was transferred to our
      hospital from a nearby hospital because of right thalamic hemorrhage evident on
      CT. She had been suffered from fever and headache for five days. Neurological
      examination on admission revealed somnolence, rigidity in the neck and
      extremities, and bilateral Babinski signs. Then she developed decorticate
      rigidity in a day. On brain MRI four hours after admission, T2-hyperintese
      lesions were demonstrated in the bilateral thalamus in addition to hemorrhagic
      change of the right thalamus on the initial CT. No pleocytosis was evident on
      cerebrospinal fluid examination at admission. Follow-up MRI on the fifth hospital
      day, however, revealed expansion of the lesions bilaterally to the medial
      temporal lobes including amygdala, hippocampus and insular cortex. The diagnosis
      of herpes simplex encephalitis was established by PCR of cerebrospinal fluid on
      the same day. After immediate treatment with acyclovir and ara-A, she gradually
      became conscious and could respond to simple conversation. This was an unusual
      case of herpes simplex encephalitis originating from bilateral thalamic lesions
      on brain imaging. We should consider thalamus as a primary lesion in herpes
      simplex encephalitis.

PMID- 15960175
TI  - [Evaluation of neurosonography for a case of brainstem transient ischemic attack
      (TIA) due to proximal subclavian artery stenosis, with favorable outcome after
      axillo-axillary bypass grafting].
AB  - We report an 82-year-old man with crescendo brainstem TIA and left upper-limb
      ischemia due to the left proximal subclavian artery stenosis. Angiography
      revealed that the left proximal subclavian artery was stenotic. The right
      vertebral artery was considered to be aplastic or occlusive. Neurosonography,
      especially the echo-Doppler study of the left vertebral artery, showed that the
      subclavian artery steal phenomenon did not occur. This study has enabled us to
      opt for axillo-axillary bypass. We preferred to avoid percutaneous transluminal
      angioplasty in order to avoid the risk of embolization. The patient received the
      axillo-axillary bypass operation. He has been free of TIAs and the left upper
      limb ischemia since the surgery. We have evaluated his blood circulation fully,
      by comparing his state before and after the axillo-axillary bypass grafting.

PMID- 15960176
TI  - [A case of postpartum cerebral angiopathy with intracranial hemorrhage and
      subarachnoid hemorrhage immediately after delivery].
AB  - A 32-year-old woman, gravida 0, para 0, was admitted for delivery at 40 weeks of
      gestation. She had no history of headache, hypertension, and toxemia. She was
      delivered of a healthy boy. Although she was given no medication during normal
      delivery, she suddenly became drowsy and developed left hemiparesis immediately
      after delivery. Computed tomographic (CT) scan of the brain performed on the
      admission day revealed a subarachnoid hemorrhage and right putaminal hemorrhage.
      A 4-vessel cerebral angiogram demonstrated multiple irregular narrowing of the
      anterior cerebral arteries, middle cerebral arteries, and posterior cerebral
      arteries. Her conditions seemed to improve without any medication, and the
      multiple stenoses were no longer observed by angiography in a follow-up
      examination. On the basis of these observations, she was diagnosed as having
      postpartum cerebral angiopathy (PCA). Pathogenesis of PCA still remaing unclear
      to date an ergot alkaloid derivate (ergonovine) and the hydrogenated form of the
      powerful vasoconstrictor ergot (bromocriptine) have been reported as cause of
      PCA. We will classify PCA into 3 categories: eclampsia, secondary PCA, and
      primary PCA. "Primary PCA" is of unknown etiology, "secondary PCA" results from a
      known etiology such as drugs, and "eclampsia" is a PCA with toxemia of pregnancy.
      We report here, that PCA may occur even in a normal pregnant woman who was given
      no medication, and should be considered in the diagnosis of postpartum cerebral
      vascular diseases in women.

PMID- 15960177
TI  - [An adult case of congenital fiber type disproportion (CFTD) with
      cardiomyopathy].
AB  - A 30 year-old man with CFTD was reported. He had normal motor milestone during
      infancy but had been poor at sports. At 28, he experienced exertional and
      nocturnal dyspnea and had been diagnosed as having dilated cardiomyopathy. At 29,
      a cardiac pace-maker was implanted because of the complete atrio-ventricular
      block. Around that time, he began to notice limb muscle weakness. Examination at
      30 showed mild diffuse muscle atrophy and weakness at the torso and limbs. No
      dysmorphic features or joint contractures were noted. His serum CK was normal. A
      histochemical study of his muscle biopsy showed type 1 fiber predominancy (64.6%)
      and that the mean diameter of type 1 fibers was smaller than that of type 2 by
      14.6% (36.9 microm vs. 42.3 microm). Results of immunostaining of dystrophin,
      emerin, laminA/C, alpha, beta, gamma, delta-sarcoglycan or dysferlin were normal.
      He was diagnosed as having CFTD because there were no histochemical abnormalities
      which characterize other congenital myopathies except for the type 1 predominancy
      and atrophy.

PMID- 15960178
TI  - [Cardioembolic stroke due to mitral annular calcification with a mobile
      component].
AB  - We report here a 50-year-old man on maintenance hemodialysis who presents right
      hemiparesis, aphasia. MRI diffusion weighted image showed an increased signal
      intensity in the area of the left middle cerebral artery. Transthoracic and
      transesophageal echocardiography revealed a mitral annular calcification (MAC)
      with a mobile component. After treated with heparin, follow-up echocardiography
      demonstrated a decrease in the size of the mobile component, but not disappeared.
      Intraoperative findings showed calcified attachment on the posterior mitral
      valve. This patient was diagnosed as having cardioembolic stroke due to a MAC
      with a mobile component.

PMID- 15960179
TI  - [MRI and SPECT findings in a case of metronidazole-induced reversible acute
      cerebellar ataxia].
AB  - A 69-year-old man was referred to our department because of acute onset nausea,
      vomiting, dysphagia, dysarthria and gait disturbance. He had a 50-day-history of
      amebic dysentery and had been treated with 1,500 mg metronidazole per day.
      Neurological examination revealed dysphagia, ataxic speech, ataxia of the left
      extremities and the trunk, and hyperactive deep tendon reflexes in all
      extremities. Sensory impairment of all modalities was apparent in a glove and
      stocking pattern, with mild paresthesia. Brain MRI showed T2 high signal lesions
      in the bilateral cerebellar dentate nuclei, more markedly on the left. On brain
      SPECT, obvious low blood perfusion was observed in the left cerebellar
      hemisphere. These findings well explained the ataxia of the left limbs. One month
      after discontinuing metronidazole, the cerebellar ataxia, dysphagia and MRI
      abnormalities completely cleared. Therefore, central nervous system damage
      induced by metronidazole is considered reversible. In spite of the presence of
      the MRI lesion in the right dentate nucleus, the patient had no ataxia of the
      right extremities and there was no hypoperfusion in the right cerebellar
      hemisphere. Thus, metronidazole does not appear to have a direct neurotoxic
      effect on the central nervous system. On the other hand, nerve conduction studies
      showed axonal polyneuropathy, which was not improved one month after cessation of
      the drug; thus metronidazole seems to exert more damage on peripheral nerves.

PMID- 15960180
TI  - [Late onset hemiparkinsonism-hemiatrophy syndrome: a case report].
AB  - Hemiparkinsonism-hemiatrophy syndrome (HPHA) is a rare form of parkinsonism,
      characterized by unilateral parkinsonism, ipsilateral body atrophy and early age
      of onset. We report a 59-year-old woman with hemiatrophy of her face and upper
      limb on the left side presenting progressive hemiparkinsonism. Most of the HPHA
      patients have early age of onset, however, HPHA patients with age of onset over
      50 years old have been reported. The clinical features of CBD are partly similar
      to those of HPHA, therefore it is important to consider HPHA as differential
      diagnosis of CBD even if the onset is late. In our patient, hemiatrophy was
      useful to differentiate HPHA from CBD. In previous reports, there was a
      difference between the dopamine D2 receptor binding capacity of CBD and that of
      HPHA. While the dopamine D2 receptor binding capacity of CBD was decreased
      asymmetrically, that of HPHA was not decreased. The PET finding of our patient
      revealed that asymmetrical reduction of [11C]-CFT uptake, meaning unilateral
      dopaminergic presynaptic hypofunction. However, [11C]-raclopride uptake, which
      assesses dopamine D2 receptor binding capacity, was normal. These PET findings
      are consistent with previous reports on HPHA. In our patient, hemiatrophy and PET
      findings were useful to diagnose HPHA.

PMID- 15960181
TI  - Effect of keto-acidosis on seizure occurrence in diabetic patients.
AB  - It has been observed anecdotally that diabetics are usually non-ketotic at the
      time of their seizure presentation. In order to establish some validity on this
      observation, we reviewed the medical records of patients with diagnoses of
      diabetes and seizure. Study subjects were diabetics presenting with seizures.
      Control subjects were random sampling of all diabetics. In 51 diabetics
      presenting with seizures, 38 were nonketotic and 13 were ketotic. In the control
      group of 119 diabetics, 63 were non-ketotic and 56 were ketotic. There were no
      significant differences in the serum levels of glucose, sodium, potassium,
      chloride, and calcium between the seizure and control groups. Multiple regression
      analysis showed that non-ketotic patients were at risk for developing seizures
      with an odds ratio of 4.03 (p=0.001). Male sex and type 1 diabetes were also risk
      factors while age was not a risk factor. Keto-acidosis may play a role in
      preventing epileptic seizures from occurring in diabetic patients.

PMID- 15960182
TI  - Go with the flow.

PMID- 15960183
TI  - West Nile virus.

PMID- 15960184
TI  - Pay for performance.

PMID- 15960185
TI  - MSMA collaborates with the Mississippi Medicare Health Support Program.

PMID- 15960186
TI  - It's a wonderful life.

PMID- 15960187
TI  - Fish versus aCGH.

PMID- 15960188
TI  - Antibiotic-removal devices defended.

PMID- 15960189
TI  - Medicine must be a "calling".

PMID- 15960190
TI  - Mosquito-borne flaviviruses and human disease.

PMID- 15960191
TI  - Understanding the natriuretic peptides.

PMID- 15960192
TI  - Ten instruments that changed the lab.

PMID- 15960193
TI  - SeraCare's CSO Mark Manak accents global blood safety.

PMID- 15960194
TI  - Privacy issues restrict lab blogging.

PMID- 15960195
TI  - [Development and clinical use of autohemotransfusion during elective surgeries
      for severe locomotor system diseases].
AB  - Autohemotransfusion is applied widely in the Division of Orthopedic Surgery of
      Moscow Regional Research Clinical Institute during elective reconstructive
      surgeries on the locomotor system. The paper shows that the method allows 90%
      reduction in donor blood transfusion, and its application to orthopedic patients
      is effective, provided that indications for it are determined correctly.

PMID- 15960196
TI  - [Cytokines as a diagnostic and therapeutic tool in patients with myocarditis].
AB  - One of the leading causes of autoimmune myocardial lesion in patients with
      myocarditis is disbalance between pro-inflammatory and anti-inflammatory
      cytokines, leading to the loss of functional tolerance to certain myocardial
      autoantibodies, and activation of autoreactive T-lymphocytes, which are able of
      myocardial cytotoxicity. The authors have conducted studies, which have shown
      that malignant myocarditis is characterized by abrupt increase of TNF-alfa and
      IFN-alfa basal serum levels, while at the same stage of the disease in patients
      with benign myocarditis only moderate increase of TNF-alfa level is observed, and
      IFN-alfa concentration is within normal limits. Abrupt increase of the cytotoxic
      activity of lymphocytes, activated by IL-2 (LAK-cells), is a feature of malignant
      myocarditis. In this category of patients the studies have found pronounced
      disbalance between cytokine serum levels, with abruptly increased levels of both
      cytokines which activate cytotoxic reactions (TNF-alfa, IFN-alfa, IL-1 alfa, IL-1
      beta, IL-12), and cytokines which stimulate humoral immunity (IL-4 and IL-6), and
      increase of antimyocardial autoantibody concentration. Further research into the
      role of cytokines in myocarditis pathogenesis would allow grounded
      cytokinotherapy and application of immunomodulators, activating cytokine
      production.

PMID- 15960197
TI  - [Vascular endothelial growth factor in patients with prostate cancer and benign
      prostatic hyperplasia].
AB  - The authors examined 25 patients with prostate cancer (PC) and 36 patients with
      benign prostatic hyperplasia (BPH). In the group of patients with morphologically
      verified PC mean serum level of vascular endothelial growth factor (VEGF) was
      significantly higher than in patients with BPH (p < 0.05). The study demonstrated
      strong negative association between VEGF and prostate specific antigen (PSA)
      levels (r = 0.72, p < 0.05) in PC patients. There was no association between VEGF
      serum level and the stage or malignancy of PC (Gleason score). In benign
      prostatic glands moderate VEGF expression was observed only in basal cells,
      whereas in cases of PC all tumor cells displayed active VEGF expression; the
      difference was significant (p < 0.05). High serum VEGF levels and its active
      expression in patients with PC suggest an important role of angiogenic factors in
      the pathogenesis of this disease. The negative association between VEGF and PSA
      serum levels in PC indirectly confirms antiangiogenic activity of PSA, shown
      before.

PMID- 15960198
TI  - [Contemporary low-invasive, videoendoscopic and organ-sparing abdominal
      operations].
AB  - The paper presents the results of low-invasive, videosurgical, and organ-sparing
      operations, developed and performed by the authors. Original low-invasive
      techniques of external, external-and-internal and internal bile-duct drainage,
      and bile-duct endoprosthesis replacement have been performed in 25 patients with
      benign and malignant bile-duct strictures. Transcutaneous puncture drainage
      operations, including those combined with an original method of transdrainage
      sclerotherapy with nitric oxide, have been performed in 93 patients with
      postnecrotic pancreatic cysts. Endoscopic virsungotomy have been performed as
      part of the complex treatment of 43 patients with external pancreatic fistulas
      and 14 patients with polycystic head of pancreas. X-ray endovascular embolization
      has been performed in 7 patients with internal arterio-pancreatic fistulas.
      Program laparoscopic abdominal cavity sanation by an original method have been
      performed in 50 patients with diffuse peritonitis. The results of the study
      demonstrate high effectiveness of the methods, which in most cases can be applied
      as an alternative to conventional surgical interventions.

PMID- 15960199
TI  - [The role of gastroesophageal reflux in malignization of post-burn and peptic
      esophageal strictures].
AB  - The subjects of the study were 221 patients with cicatrical esophageal
      strictures. 62 (28.5%) patients had peptic strictures, and 159 (71.9%)--post-burn
      strictures. 67 (30.3%) patients underwent esophageal resection with one-stage
      intrapleural esophagoplasty with the stomach, 152 (68.8%) patients--gullet
      bougienage in combination with surgical intervention or as an only treatment. The
      study revealed 8 cases of squamous cell carcinoma in patients with post-burn
      strictures, and 3 cases of squamous cell carcinoma in patients with peptic
      strictures. In 2 cases the researchers found early stage of esophageal cancer
      (verrucose carcinoma)--in 1 patient with post-burn stricture and 1 patient with
      peptic stricture. The results suggest an important role of chronic
      gastroesophageal reflux in the oncogenesis of esophageal squamous cell carcinoma
      in patients with post-burn and peptic strictures.

PMID- 15960200
TI  - [Treatment of patients with respiratory papillomatosis: experience analysis].
AB  - The authors of the article analyze clinical observations of 240 patients with
      respiratory papillomatosis (aged 7 months to 56 years), treated in the ETN clinic
      of Moscow Regional Research Clinical Institute in 1984-2003 using endolaringeal
      microsurgical techniques, such as ultrasound desintegration and laser
      photodestruction of papillomas. Additional therapy included immunocorrection with
      T-activin and leukomax, discrete plasmopheresis, antiviral therapy with zovirax,
      and photodynamic therapy. Having compared various methods and their combinations,
      the authors conclude that "clinical recovery" (no relapses within more than 2.5
      years), was achieved in 41.4 +/- 0.5% - 77.8 +/- 0.2% patients.

PMID- 15960201
TI  - [Biospectroscopy-based endoscopy with low-intensive laser radiation for
      differential diagnostics and treatment of peptic ulcer].
AB  - The article covers results of application of biospectrometry-based endoscopy with
      low-intensive He-Ne laser radiation in complex therapy of torpid esophageal,
      gastric, and duodenal ulcers. The authors are the first to offer a method based
      upon individual biophotometric control (autofluorescence, oxigination), which
      allows verification of the ulcerous process character, individual optimization of
      treatment and objective control of ulcer regression.

PMID- 15960202
TI  - [Ways of surgical technique optimization and prevention of hip endoprosthesis
      dislocation following total hip arthroplasty].
AB  - The article presents experience concerning intraoperative prevention of hip
      endoprosthesis dislocation, gained in the orthopedic surgical clinic of Moscow
      Regional Research Clinical Institute. The results of 1208 total articular
      replacements allowed the development of intraoperative dislocation-preventive
      measures, taking into account the approach to the hip joint, necessary
      mobilization of articular ends, the relative position of total endoprosthesis
      components. The cases of hip endoprosthesis dislocation were analyzed. The
      offered preventive measure system allowes reduction in total endoprosthesis
      dislocation rate down to 1.5%.

PMID- 15960203
TI  - [Modern technologies in pediatric diagnostics and intensive care].
AB  - New technologies of diagnostics of post-operative period complications in
      newborns (measure of procalcitonin level, serum wedge-shaped dehydration method),
      as well as introduction of discrete plasmopheresis and fiber-optic bronchoscopy
      via the laringeal mask, present necessery additions to traditinally used methods
      of treatment in a children's intensive care unit, improving the results of its
      work.

PMID- 15960204
TI  - [Linear and adhesive phenotype of tumor lymphocytes and clinical course of
      chronic leucosis].
AB  - Determination of chronic lymphatic leukemia immunological phenotype, performed by
      the authors, was based upon the study of quantitative expression of membrane
      differentiation antigens on peripheral blood lymphocytes. The research included
      study of co-expression of adhesion molecules, belonging to the following
      families: beta 2 integrins (CD 11 beta, CD 18), immunoglobulins (CD 50), and CD
      38 on tumor blood B-lymphocytes of various CD-types and T-lymphocytes in chronic
      leucosis. The authors developed a functional model of trans-endothelial migration
      of peripheral blood lymphocytes in chronic chronic lymphatic leukemia, taking
      into account their membrane adhesive characteristics and serum level of CD 50.
      The researchers determined clinical importance of the expression of linear and
      adhesive antigens on peripheral blood lymphocytes, and soluble HLA-1 (sHLA-1)
      serum levels in patients with chronic lymphatic leukemia.

PMID- 15960205
TI  - [A new view of approaches to diagnostics and treatment of Kaposi's sarcoma].
AB  - The paper contains literature data and the results of author's own observations,
      devoted to the clinical manifestations, ethiology and pathogenesis of Kaposi's
      sarcoma. An algorithm of diagnostics of the disease and methods of treatment are
      offered, which are developed taking into account the type of the disease, its
      form, the extent of the pathologic process and immunological parameters.

PMID- 15960206
TI  - [Increasing the effectiveness of skin cancer T(2-3) N0M0 radiotherapy by use of
      radiosencibilizers].
AB  - The paper presents an attempt to increase the effectiveness of radiotherapy of
      locally advanced skin cancer by use of radiomodifiers. With this aim the
      researchers used metronidozol (MZ) and low-intensive laser emission (LILE), whoes
      radiosensibilizing activity is based on overcoming radioresistance of tumor
      hypoxic cell fraction. In order to increase MZ concentration in the tumor and
      eleminate its toxic effect the authors developed a new radiosensibilization
      technique, implying local use of a drug applicator. The technique is based on use
      of textile materials with specifed medical qualities (the method of their
      production was developed by the Scientific and Practical Association
      "Textileprogress"). The second direction of the research consisted in use of low
      intensive laser emission as a radiosensibilizer, which was considered to be
      possible due to theoretical and experimental data suggesting the LILE capability
      of activating microcirculation in tumor and surrounding tissues. According to the
      authors of the article, the improvement of tumor microsirculation must increase
      tumor cell oxygenation, thus increasing their radiosensitivity. Applying
      radiosensibilization of hypoxic cells with MZ and LILE in radiotherapy of T2
      basal cell and squamous cell carcinomas with the tumor size 4-5 cm and T3 tumors
      using original dose fractioning regimens (TFD 72 to 73 Gy) allows significant
      improvement of immediate treatment results without increase in local
      radioreactions and without substantial influence of the recurrence rate.

PMID- 15960207
TI  - [Academic Council of Red Army Central Medical Department during Great Patriotic
      War].

PMID- 15960208
TI  - Prevalence of genital prolapse in Thai menopausal women (using new
      standardization classification).
AB  - BACKGROUND: There is an increasing number of menopausal women in Thailand
      (estimation of 5 million women). There is no published data on the prevalence of
      genital prolapse among Thai menopausal woman. So the authors created this
      hospital based study to identify the magnitude of this problem in Thai menopausal
      women. OBJECTIVE: To study the prevalence and symptoms of genital prolapse in
      Thai menopausal women attending the menopausal clinic in King Chulalongkorn
      Memorial Hospital. STUDY DESIGN: Descriptive study (Cross-sectional study).
      MATERIAL AND METHOD: Two hundred and fifteen Thai menopausal women attending the
      menopause clinic at King Chulalongkorn Memorial Hospital from the 1st of January
      to the 28th of February 2004 were recruited. Urinary symptoms history taking and
      pelvic examination were done. The severity of any prolapse was classified using
      International Continence Society classification. RESULTS: Prevalance of Thai
      menopausal women having any type of genital prolapse was 43.3%. Anterior vaginal
      wall prolapse and superior vaginal prolapse were the two highest prevalences of
      genital prolapse (29.3% and 14.9%). The prevalence of genital prolapse increased
      by the menopausal age. The two leading symptoms were stress incontinence and
      vaginal outlet relaxation (89.3% and 51.6%). CONCLUSION: From the present study,
      the authors found the prevalence of any genital prolapse (43.3%) and stress
      incontinence(89.3%) among Thai women attending menopausal clinic in King
      Chulalongkorn Memorial Hospital. The authors strongly recommend pelvic
      examination and urinary-symptoms history taking to evaluate the severity of
      genital prolapse.

PMID- 15960209
TI  - The three years results of tension free vaginal tape (TVT) for the treatment of
      stress urinary incontinence in Thai women.
AB  - OBJECTIVE: To evaluate the three years result of TVT procedure in Thai women with
      genuine stress urinary incontinence (SUI). MATERIAL AND METHOD: Sixty three
      women, aged 35 - 71 years attending the gynecology clinic at King Chulalongkorn
      Hospital from February 2000 to May 2001 were recruited in the present study. Pre
      operative evaluation included history taking and physical examination. All had
      stress urinary incontinence urodynamically confirmed genuine stress urinary
      incontinence and were treated with TVT Follow up at 3, 6, 12, 18, 24, 30 and 36
      months were scheduled after surgery. RESULTS: The mean +/- SD of operative time
      for TVT was 32.3 +/- 10.0 min the mean +/- SD of hospitalization was 1.8 +/- 2.0
      days. Two patients had bladder perforations by the trocar without severe bleeding
      and needed no reparation. No healing defect or rejection of the prolene mesh was
      found. The cure rate and improved rate were 95.2% and 4.8% respectively (60 from
      63 cases) at 3 years follow up. CONCLUSION: The three years results revealed that
      TVT was effective and safe in the treatment of SUI in Thai women.

PMID- 15960210
TI  - Study of the prognostic value of the pregnant nutrition graph (Vallop Curve) to
      predict the incidence of low birth weight infants.
AB  - OBJECTIVE: To test the prognostic value of the pregnant nutrition graph (Vallop
      Curve). DESIGN: Prospective and comparative study. SETTING: Department of
      Obstetrics and Gynecology, Prangnangklao Hospital. SUBJECT: 510 cases who
      attended the antenatal care clinic and delivered at Prangnangklao Hospital from
      January 2004 to July 2004. MATERIAL AND METHOD: Height, weight and pre-pregnancy
      body mass index (BMI) of the women were recorded and classified BMI of each into
      3 groups, low BMI (< 19.8) normal BMI (19.8 - 26.0) and high BMI (26.1 - 29.0.)
      The weight of the pregnant women in each gestational week was calculated as
      percentage of standard BMI at 21 and plotted in a Vallop Curve. The data was
      analyzed by using an Anova Test and Wilson Method to find association. A p-value
      of < 0.05 was regarded as significant. OUTCOME EVALUATION: Birth weight curve,
      below the 2,500 gm line and above the 2,500 gm line. RESULTS: The mean birth
      weight of low BMI was 2,541.70 +/- 276.89 gm. The mean birth weight of normal BMI
      was 3,021.30 +/- 318.61 gm. The mean birth weight of high BMI was 3,520.00 +/-
      250.65 gm. There was a significant difference in weight by the Anova Test.
      Sensitivity was 65.6%. Specificity was 87.4%. Positive predictive value was
      42.9%. Negative predictive value was 94.7%. P-value was < 0.001 at 95% confident
      interval by the Wilson Method. CONCLUSIONS: The Vallop Curve may be useful to
      predict the incidence low birth weight infants, but in the future the Vallop
      Curve may be changed corresponding to change of socio-economic status and also to
      simplify it's method of usage.

PMID- 15960211
TI  - Diclofenac intramuscular single dose to decrease pain in post operative Caesarean
      section: a double blind randomized controlled trial.
AB  - OBJECTIVE: To compare the use of diclofenac intramuscular single dose to decrease
      pain in post operative Caesarean section with none used. STUDY DESIGN: A double
      blind randomized controlled trial. SETTING: Department of Obstetrics and
      Gynecology, Ranong Hospital. SUBJECTS: Sixty-four patients who underwent post
      operative Caesarean section in Ranong Hospital from October 2003 to March 2004.
      INTERVENTION: The subjects were randomized by allocation to receive diclofenac
      intramuscular or placebo, both groups received morphine by Patient Controlled
      Analgesia (PCA). MAIN OUTCOME MEASURES: Amount of morphine sulfate used, in both
      groups by Patient Controlled Analgesia (PCA) and level of pain using Visual
      Analog Score (VAscore). RESULTS: Morphine was used significantly less in the
      group of patients who had diclofenac intramuscular single dose in post operative
      Caesarean section but the level of pain was not significantly different.
      CONCLUSION: A single dose of diclofenac intramuscularly decreases the use of
      morphine during the in post operative period of Caesarean section.

PMID- 15960212
TI  - Reducing cesarean delivery rates: an active management labor program in a setting
      with limited resources.
AB  - OBJECTIVE: To determine the effect of an active management of a labor program on
      the rate of cesarean section and labor outcomes in low-risk nulliparous
      pregnancies in a setting with limited resources. MATERIAL AND METHOD: Nine
      hundred and seventy-five low risk nulliparous pregnant women were randomized to
      receive either active management of a labor program (n = 325) or conventional
      management (n = 650). The rate of cesarean section and labor outcomes were
      compared between the two groups using Chi-square and t-tests. RESULTS: The
      subjects in the active management program had significantly shortened first stage
      of labor and total duration of labor compared with the conventional group (538.0
      +/- 242.9 min vs 589.4 +/- 263.8 min, p < 0.05, 539.3 +/- 261.4 min vs 610.3 +/-
      264.4 min, p < 0.001, respectively). There was no statistical difference found in
      the rate of cesarean section and other labor outcomes. CONCLUSION: The active
      management program shortened the first stage and duration of labor in low-risk
      nulliparous pregnant women.

PMID- 15960213
TI  - Body temperature and mortality in acute cerebral infarction.
AB  - BACKGROUND AND OBJECTIVE: In animal models, a rise in body temperature after
      cerebral ischemia consistently produces more extensive brain damage. In humans,
      however the relationship between body temperature and stroke outcome has been far
      less extensively investigated, providing conflicting results. The objective of
      the present study is to determine whether body temperature recorded during the
      first 72 hours after admission is an independent predictor of mortality in acute
      cerebral infarction. MATERIAL AND METHOD: The medical records of patients
      admitted within 48 hours of onset of symptoms to Prasat Neurological Institute
      between 1 January 2002 and 31 December 2003, with a diagnosis of cerebral
      infarction, confirmed by CT or MRI of the brain were retrospectively studied. The
      relationship between the highest temperature recorded during the first 72 hours
      after admission and mortality during hospital stay was evaluated. Multiple
      logistic regression analysis included relevant confounders and potential
      predictors such as gender, age, hypertension, diabetes, smoking, previous stroke,
      ischemic heart disease, atrial fibrillation, consciousness and infections was
      performed. RESULTS: There were 332 patients included in the present study. During
      the first 72 hours after admission, 88 (26.5%) patients had fever (> 37.5 degrees
      C). The highest temperature recorded during the first 72 hours after admission
      was a significant predictor of in hospital mortality in the final multivariate
      logistic regression model. For each 1 degree C increase in body temperature the
      odd ratio of mortality rose by 3.95 (OR, 3.95; 95%CI, 1.84 - 8.45). CONCLUSION:
      In the present study, the highest body temperature recorded during the first 72
      hours after admission was shown to be a significant predictor of mortality in
      acute cerebral infarct patients.

PMID- 15960214
TI  - Management of tracheobrochial injuries: a 10-year experience at Ratchaburi
      hospital.
AB  - BACKGROUND AND OBJECTIVE: Tracheobronchial injuries are rare but life
      threatening. Their successful diagnosis and treatment require a high level of
      suspicion and early surgical repair The authors review their experience in
      managing these injuries over the past 10 years. MATERIAL AND METHOD: Patients who
      were admitted to the Thoracic Surgical Unit, Ratchaburi Hospital and treated for
      tracheobronchial injuries from 1993 to 2004 were included in the present study.
      Hospital records were reviewed on mechanism of injury, clinical presentation,
      diagnosis, management and outcome. RESULTS: The present series comprised of 11
      tracheobronchial injury patients. Causal mechanism of injury was 4 blunt and 7
      penetrating injuries. 4 of them with blunt injury, there were 3 right main
      bronchial disruptions, 1 minor cervical laceration. Presenting signs included
      dyspnea in 4 and subcutaneous emphysema in 3. 1 of them had massive air leak.
      Radiographic finding were pneumomediastinum in 3. Pneumothorax in 2, Atelectasis
      of right lung in 1. All of the right bronchial disruptions had primary repair
      with reanastomosis in 2 and resection of stenotic bronchus with reanastomosis in
      1; this patient developed empyema thoracis with Acinetobacter iwoffii as a result
      of delayed diagnosis (40 day). One patient with minor cervical laceration
      underwent conservative treatment. All patients with blunt injuries were
      discharged with a normal patency of airway. 7 patients with penerating injuries,
      there were 4 cervical, 1 cervical associated with esophageal injury, 1 combined
      cervical-thoracic type of injuries and 1 Thoracic injury. Presenting signs
      included dyspnea in 7 and subcutaneous emphysema in 6. The radiographic finding
      were pneumomediastinum in 5 pneumothorax in 4, one patient underwent tracheal
      reanastomosis. The rest of six patients underwent immediate primary repairs. One
      patient with cervical knife stap wound died 4 hours postoperatively of
      hemoptysis, progressive hypoxia and aneuria, 6 of them were recovered with a
      normal patency of airway CONCLUSION: The authors concluded that, result of
      treatment for tracheobronchial injury should depend upon the mechanism of injury,
      early recognition, early diagnosis and appropriate surgical intervention. Delay
      in diagnosis is the single most important factor-influencing outcome. Common
      complications in the early phase were hypoxia, organ failure while in the late
      phase were sepsis, tracheal or bronchial stenosis, mediastinitis and chronic
      bronchopleural fistula, etc.

PMID- 15960215
TI  - Ecstasy (MDMA) ingestion related with severe hyponatremia in patients with mild
      head injury.
AB  - The occurrence of severe hyponatremia is an unusual complication in patients with
      a mild head injury. Between December 2001 and January 2003, 1147 patients with a
      mild head injury were reviewed Only patients who presented with deterioration of
      consciousness or seizure due to hyponatremia, confirmed by serum investigation,
      were further evaluated, presenting features and clinical courses. The results
      revealed only 3 patients developed severe hyponatremia following a mild head
      injury. Surprisingly, all of them had a recent history of ecstasy (MDMA) use, as
      well as hyponatremia which didn't develop until the episode of a mild head
      injury. In the present report, the associated mechanisms of both conditions of
      severe hyponatremia are discussed and the literature is reviewed.

PMID- 15960216
TI  - Incidence and risk factors of iron deficiency anemia in term infants.
AB  - OBJECTIVE: To compare the incidence of iron deficiency anemia (IDA) between
      breast-fed (BF) and formula-fed (FF) infants and to identify the risk factors of
      IDA in these infants. DESIGN: Cohort study. MATERIAL AND METHOD: A study of 140
      full- term infants (70 BF and 70 FF) was conducted at BMA Medical College and
      Vajira Hospital from February 2002 to November 2003. All infants were followed at
      the age of 1, 2, 4, 6, 9 and 12 months for growth and developmental assessment.
      Blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct) and mean
      corpuscular volume (MCV) at 9 - 12 months; and infants with Hb < 11.0 g/dl were
      further investigated for the cause of anemia. RESULTS: The mean values of Hb,
      Hct, MCV and serum ferritin of BF infants were 10.8 g/dl, 32.8%, 70.9fl and 16.7
      ng/ml respectively, which were significantly lower than those of FF infants (11.4
      g/dl, 35.1%, 73.3fl, and 36.9 ng/ml, p < 0. 05). Anemia was found in 27 BF
      infants (38.6%) compared with 10 FF infants (14.39%). The incidence of IDA in BF
      infants was significantly higher than FF infants (25.7% vs 2.9%, p < 0.001). Risk
      factors of IDA included low birth weight, breastfeeding and inadequate
      complementary food (adjusted RR (95% CI): 3.1(1.1 - 9.1), 6.3(1.5 - 25.0),
      7.7(2.8 - 20.0), respectively). CONCLUSION: IDA is more prevalent in BF than FF
      infants. Risk factors of IDA are low birth weight, breastfeeding and inadequate
      complementary food. Prevention of IDA in infants should be achieved through
      adequate iron-rich complementary food and screening for Hb or Hct at 9 - 12
      months of age in high risk infants.

PMID- 15960217
TI  - Efficacy of weaning protocol in medical intensive care unit of tertiary care
      center.
AB  - OBJECTIVE: To evaluate the efficacy of the protocol-directed weaning from a
      mechanical ventilator compared to physician-directed weaning. MATERIAL AND
      METHOD: A comparative study between retrospective studies of physician-directed
      weaning as controls (N = 198) reviewed from July 2000 to July 2002 and the
      prospective studies of protocol-directed weaning as intervention (N = 196)
      enrolled from October 2002 to October 2003 in the medical ICU of Maharaj Nakorn
      Chiang Mai Hospital, tertiary care center of northern Thailand. Study results
      were concluded by Fisher's exact test. RESULTS: Baseline characteristics data of
      both groups including sex, age, illness severity which demonstrated by APACHE II
      score and PaO2/FiO2 ratio, causes of respiratory failure and mode of mechanical
      ventilation used were similar. The duration of mechanical ventilation before
      weaning was 5.89 +/- 3.71 days in the protocol-directed group and 7.41 +/- 5.54
      days in the physician-directed group (p < 0.05). Weaning duration in the protocol
      directed group was significantly shorter than the physician-directed group (14.58
      +/- 16. 98 hours VS 47.09 +/- 38.23 hours; p < 0.05). Kaplan-Meire analysis
      demonstrated that patients in the protocol-directed group had significantly
      shorter durations of mechanical ventilation compared to patients in the physician
      directed group (p = 0.001, log-rank test). The ICU LOS was significantly shorter
      in the protocol-directed group (7.91 +/- 4.71 vs 11.53 +/- 7.80 days; p < 0.05).
      The 28 days mortality rate and the incidence of hospital acquired pneumonia
      seemed to be less in the protocol-directed group (4.60% vs 6.10% and 5.60% vs
      10.10% consecutively) and reintubation rate seemed to be higher in the protocol
      directed group (6.1% vs 4.5%) than the physician-directed group but differences
      were not significant (p > 0. 05). CONCLUSION: Protocol-directed weaning proved to
      have more efficacy in weaning patients from a ventilator than physician-directed
      weaning in terms of weaning duration and ICU length of stay without a
      deteriorating effect to the patients.

PMID- 15960218
TI  - Squamous cell carcinoma arising in chronic ulcers in leprosy.
AB  - Squamous cell carcinoma (SCC) arising in chronic ulcers of leprosy patients is
      uncommon. A retrospective analytical study of 416 biopsy specimens of chronic
      ulcers during 1976 - 2000 occuring on the extremity of leprosy patients was
      performed. Pathologic examination showed that 217 specimens (52.2%) were reported
      as pseudoepitheliomatous hyperplasia (PH). A total of 102 (24.5%) specimens
      reported as SCC, involving 100 individual patients (69 males, 31 females). SCC
      was localized on the lower extremity in 87 specimens (85.3%). No significant
      difference was observed between left and right foot using Chi-square test. The
      sole was the commonest site of involvement, and then the heel. SCC on the upper
      extremity which was much less common, presented in 15 specimens (14.7%). The
      tumor was localized on the palm in 10 specimens (right: 9, left: 1). SCC in
      chronic ulcers of leprosy patients were much more common on the lower extremity
      than on the upper extremity. Most of the tumors on the upper extremity were
      localized on the right palm. This emphasizes the need for an active policy of
      prevention of disability in leprosy control programs.

PMID- 15960219
TI  - Accuracy of the mammographic report category according to BIRADS.
AB  - OBJECTIVE: To determine the accuracy and predictive value of the mammographic
      report according to the BIRADS categories in Songklanagarind University Hospital.
      MATERIAL AND METHOD: Mammograms of 1000 women who came to Songklanagarind
      University Hospital from June 1998 to September 1999 were reported and placed in
      category 1 for negative results, category 2 for benign lesions, category 3 for
      probably benign lesions, category 4 for suspicious lesions and category 5 for
      highly suspicious lesions. Accuracy was determined by either histology or by
      unchanged follow-up mammography within 24 months. RESULTS: The total accuracy was
      97.8%, sensitivity 62.5% and specificity 98.1%.

PMID- 15960220
TI  - Value of clinical findings, electrodiagnosis and magnetic resonance imaging in
      the diagnosis of root lesions in traumatic brachial plexus injuries.
AB  - OBJECTIVE: To evaluate the diagnostic value of clinical findings,
      electromyography and magnetic resonance imaging of root lesions in traumatic
      brachial plexus injuries MATERIAL AND METHOD: The authors clinically evaluated
      175 cervical roots (C5-8, T1) in patients with traumatic brachial plexus injuries
      then with electromyography and magnetic resonance imaging (MRI). Each finding,
      taken alone and in combination with each other, was compared with the findings of
      exploratory surgery. RESULTS: The mean correlations of the clinical findings,
      electromyography and MRI in relation to the surgical findings were 60, 87 and 70
      percent, respectively. The mean correlation was highest (90%) when the positive
      findings from the clinical, electromyographic or MRI investigations were
      combined. The correlation of the C5-6 root injuries was improved to 100% though
      the mean correlation was only 90%. CONCLUSION: The combination of clinical
      findings and electromyography correlated well with the surgical findings of root
      lesions caused by traumatic brachial plexus injury. MRI markedly improved
      identification only of C5-6 root injuries.

PMID- 15960221
TI  - Gastrointestinal and hepatobiliary manifestations in systemic lupus
      erythematosus.
AB  - OBJECTIVE: To report GI and Hepatobiliary manifestations in SLE from
      Chulalongkorn Hospital in the year 2000. MATERIAL AND METHOD: A retrospective
      study of SLE patients in the Rheumatological Clinic, Medical Department,
      Chulalongkorn University. RESULTS: A total 225 SLE patients were found being
      mainly female (93.3%). The mean age was 32.13 +/- 11.65 years and they almost all
      lived in the central part of Thailand (79.1%). At diagnosis, the majority of SLE
      cases are active vital organ (72.1%), kidney and central nervous system are the
      main organ of involvement. GI and hepatobiliary manifestations were found in
      32.89% but did not lead to SLE diagnosis. The duration between SLE diagnosis and
      first GI and hepatobiliary manifestations is 4.6 +/- 4.4 years. The 3 common
      manifestations are abnormal liver function test, diarrhea and abdominal pain,
      with the prevalance rate of 34, 17 and 11% respectively. CONCLUSION: GI and
      hepatobiliary manifestations of SLE patients in Chulalongkorn Hospital were found
      in 32.89% but were not specific and could be found in any part of the alimentary
      tract. The 3 common manifestations were abnormal liver function tests, diarrhea
      and abdominal pain which were not specific enough to diagnose SLE.

PMID- 15960222
TI  - HIV infection among substance abusers in Thanyarak Institute On Drug Abuse,
      Thailand, 1987-2002.
AB  - A study of HIV infection among substance abusers from 1987 to 2002 was performed
      in Thanyarak Institute on Drug Abuse (TIDA). From 118,676 anti HIV tests (6,076 -
      10,626 tests each year) of TIDA inpatients, 17,526 tests were positive (474 -
      2,041 tests each year) In 71,403 new substance abuse cases (3,724 - 6,184 cases
      each year), 12,401 cases were positive (17.4%), highest in 1990 28.3% and then
      decreased to 8% in the last three years. In injecting drug users (IDU), the mean
      anti HIV positivity rate was 21.7% (range 19.2 - 29.4%) higher than those among
      non IDU about 8 times 2.8% (range 1.9 - 3.6%). The HIV incidence rates were from
      inpatients that were previously anti-HIV negative, the authors found the mean
      incidence rate was 7.3% per year. Anti HIV positive cases were highest in
      injecting heroin users (IHU) about 36.8% (range 31.5 - 46.1%). Although numbers
      of IHU in Thailand have decreased in the last 6 years because of changing to use
      methamphetamine by smoking and dying from HIV subtype B'. The authors must
      continue the effective preventive programs of both avoid sharing injecting
      equipments and promoting 100% condom program to control this reservoir of HIV
      infection.

PMID- 15960223
TI  - Urinary tract calculi in southern Thailand.
AB  - OBJECTIVE: To study the epidemiology of urolithiasis in Southern Thailand.
      DESIGN: Descriptive study. MATERIAL AND METHOD: An overview of urolithiasis in
      the South of Thailand was derived from 10,344 urolithiasis patients seeking
      treatment in 14 hospitals in southern Thailand, from January to December 2000. An
      epidemiological study focused on 1,452 urolithiasis patients treated at
      Songklanagarind Hospital during the same period. Composition of calculi was
      analysed with infrared spectroscopy. RESULTS: The ratio of male to female was 1.6
      : 1 and the most common age group was 41 - 50 years. Ureteric calculi were more
      frequently found than renal calculi. ESWL was the most common treatment for upper
      urinary tract (UUT) calculi, while surgery was the most common treatment for
      lower urinary tract (LUT) calculi. The body mass index (BMI) of 48.1% was between
      18.5 - 24.9. The study of the calculi composition showed that oxalate was found
      in most UUT, and uric acid was found in most LUT CONCLUSION: Ureteric calculi
      were most common in the South of Thailand. The BMI of urolithiasis patients was
      higher than the population average.

PMID- 15960224
TI  - Factors influencing development of children aged one to under six years old.
AB  - The present study aimed at analysing factors influencing the development of
      children aged one to under six years in four provinces across Thailand. Two sub
      districts or communities were selected from each province. The population covered
      in the present study were 193 children aged one to under three years and 251
      children aged three to under six years, and their main caregivers. The data was
      collected from April to September 2000. Denver II test kit was used to test the
      child development and a questionnaire was used to collect family and child
      factors. The results of analysis using Logistic Regression found that risk
      factors for lower child development among children aged one to under three years
      were father's education at the primary school level or lower (OR = 3.0 , 95%CI =
      1.14, 7.9) and not having good household environments (OR = 2.9, 95%CI = 1.28,
      6.8). The risk factors for lower development among children aged three to under
      six years were father's education at the primary school level or lower (OR =
      3.57, 95% CI = 1.74, 7.32) and inappropriate child raising (OR = 2.72, 95%CI =
      1.48, 4.99). Families with fathers having a low level of education, inappropriate
      household environments or inappropriate child raising should receive assistance
      so that children can have appropriate development for their age level.

PMID- 15960225
TI  - The association between erectile function and severity of lower urinary tract
      symptoms.
AB  - It is unclear whether the erectile dysfunction (ED) that frequently occurs with
      lower urinary tract symptoms (LUTS) may have a common causative factor:
      sympathetic overactivity. The aim of this study was to evaluate the association
      between ED and LUTS. From June 1998 to March 2000, 75 male patients, presenting
      with LUTS, enrolled into the present study. A total of 63 patients were included
      into the study, age ranging from 51 - 74 years (mean 61.5). Allpatients completed
      an American Urological Association (AUA) symptom severity index and IIEF-5
      questionnaires. The results from the present study demonstrated that the AUA
      symptom and IIEF-5 scores do not correlate with increasing age. When the
      statistical analyses were performed for each age group, there were no significant
      differences in mean IIEF-5 values between any degree of AUA symptom score in the
      same age group (p > 0.05). The present results indicate that there is no
      association between the degree of LUTS and the erectile function. Moreover, the
      statistical analyses of the association between any degree of erectile function
      and the mean A UA symptom score either for obstructive or irritative symptoms
      revealed no significant differences (p > 0.05). The present study demonstrates
      that there is no association between BPH and erectile function in any age group,
      inconsistent with the sympathetic overactivity theory.

PMID- 15960226
TI  - Effect of attenuation correction on lesion detection using a hybrid PET system.
AB  - OBJECTIVE: The purpose of this study was to investigate the effect of attenuation
      correction (AC) on lesion detection for a hybrid PET system. MATERIAL AND METHOD:
      Experimental list-mode data were acquired from hot spheres inside a uniform
      cylindrical phantom with an elliptical cross-section using a Siemens E. CAM+ dual
      camera hybrid PET system. Spheres with inner diameters of 0.8- and 1-cm and the
      cylindrical phantom were filled with F-18 to simulate lesions with lesion-to
      background (L/B) ratios of 14:1 and 8:1, respectively, found in clinical PET
      studies. The list-mode data of each sphere size were regrouped into sinograms
      with peak-to-peak energy window settings at 30% and 20% for the 0.8- and 1-cm
      diameter lesion, respectively. They were then rebinned using the single slice
      rebinning method. Attenuation correction was applied assuming uniform
      attenuation. The sinograms with and without AC were reconstructed using 5
      iterations of OS-EM algorithm with 8 angles/ subset and postfiltered with a
      Butterworth filter with n = 5 and fc = 0.52 cycles/cm. Human observer performance
      study and localization receiver operating characteristic (LROC) analysis were
      used to evaluate the reconstructed images for maximum lesion detection. Average
      areas under the LROC curves (A(LROC)) across 8 observers obtained with and
      without AC were determined. The null hypothesis that there was no difference
      between with AC and without AC was tested using a two-tailed t-test with 95%
      confidence interval. RESULTS: The results indicated that for the 0. 8-cm lesion
      with 14:1 L/B ratio, the A(LROC) decreases from 0.66 to 0.62 when AC is applied
      as compared to without AC andfrom 0.69 to 0.63 for the 1.0-cm lesion with 8:1 L/
      B ratio, but no statistical significant difference (p > 0. 05). CONCLUSION: The
      authors conclude that for a phantom with hot lesions embedded in a uniform
      background, AC decreases lesion detectability compared to without AC using a
      hybrid PET system for small lesion sizes.

PMID- 15960227
TI  - Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS.
AB  - To determine the visual outcome, progression, and complications of patients with
      acquired immuno-deficiency syndrome-related cytomegalovirus (CMV) retinitis
      treated with intravitrealfoscarnet (2.4 mg in 0.1 ml per injection), a
      retrospective study was carried out in 193 patients. Induction therapy consisted
      of two injections a week until the lesions were inactive. Maintenance therapy
      consisted of one injection a week until relapse, then re-induction was
      instituted. In 301 treated eyes, visual acuity remained stable in 184 (61%),
      improved in 16 (5%), and decreased in 101 (34%). Of these, 15 retinal
      detachments, 13 intravitreal hemorrhages, 3 endophthalmitis, and 2 cataract
      occurred. Median time of first progression was 15 weeks. Involvement of the
      fellow eye occurred in 35% of the patients during treatment of the first eye.
      Intravitreal foscarnet appeared to be a useful alternative treatment for patients
      intolerant or unaffordable to intravenous anti-CMV drugs, but the complications
      of this treatment should also be considered.

PMID- 15960228
TI  - Detection and identification of Mycobacterium species by polymerase chain
      reaction (PCR) from paraffin-embedded tissue compare to AFB staining in
      pathological sections.
AB  - BACKGROUND: Polymerase chain reaction (PCR) is a recent, rapid and reliable
      method in the detection of causative organism. The authors tried to determine the
      possibility of using PCR technique as an alternative way to detect mycobacterial
      DNA from paraffin-embedded tissue to avoid repeated biopsy from the patient.
      MATERIAL AND METHOD: Paraffin-embedded tissue blocks, the corresponding
      histopathologic slides, and cultural results were retrospectively searched for
      according to the patient's records, the granuloma clinic, Department of
      Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok,
      Thailand from 1994-2000. One hundred and thirty-one tissue blocks and slides were
      found but only 120 cultural results were retrieved Histologic sections were
      reviewed for AFB findings and PCR was done using 16S rRNA sequences to detect M.
      tuberculosis by one-tube nested technique and multiplex PCR for M. marinum and M.
      fortuitum complex. RESULTS: The causative organisms were identified by AFB
      staining in pathologic sections 31.29%, by PCR 35.87%, and by culture 30.00% of
      tested samples. The sensitivity of PCR when compared to AFB result was 29.26%,
      specificity 61.11% but when compared to cultural results, the sensitivity of PCR
      was 66.67% and AFB sensitivity was 41.66% with specificity 76.19% and 72.61%
      respectively. CONCLUSION: The low sensitivity of the PCR method may be due to
      formalin fixation, deparaffinization process, DNA extraction method, the use of
      16S rRNA-based primers and the length of the expected product, and the tissue
      type that may have Taq polymerase inhibitor. Therefore, PCR should be used to
      augment the information of the conventional method in the diagnosis of
      mycobacterial infection.

PMID- 15960229
TI  - Carcinoma of the external auditory canal.
AB  - Carcinoma of the external auditory canal is one of the most inaccessible areas of
      the body. It is a rare malignant neoplasm with an aggressive nature and an
      overall poor prognosis. In a ten year period, 16 patients were treated in King
      Chulalongkorn Memorial Hospital. From TNM staging proposed by the University of
      Pittsburgh, the authors found T1 = 1, T2 = 6, T3 = 5, T4 = 4 cases. In 14
      patients who were operated on (radical mastoidectomy in 8, lateral temporal bone
      resection in 5, sleeve resection in 1), 7 had cured (50%), 7 were recurrence. 6
      cases of recurrence developed in patients with radical mastoidectomy, 1 case with
      lateral temporal bone resection. The overall cure rate in stage I-II = 85.71%
      (6/7) but only 11.11% (1/9) in the advanced stages (III-IV). The present data
      suggest that in early cancer (stage I-II) the lateral temporal bone resection
      with postoperative radiation is better than radical mastoidectomy with
      postoperative radiation.

PMID- 15960230
TI  - Labial leiomyoma: a case report.
AB  - Leiomyoma is common in the myometrial layer of the uterus, and rarely found in
      other genital organs. Previous reports show multiple sites of leiomyoma outside
      the uterus eg. vagina, oral mucosa or mandible vascular leiomyoma. Leiomyoma is
      normally a benign smooth muscle tumor and behaves as a hormone sensitive tumor
      Leiomyomas develop during the reproductive age and regress after menopause. The
      case of a 25 year old female with a large left labial leiomyoma presented as
      Bartholin's cyst. Illustrates the diagnostic difficulties in such cases. The
      management in this case was surgical excision. The definite diagnosis was
      confirmed by histologic examination as a labial leiomyoma.

PMID- 15960231
TI  - Rabies and dog population control in Thailand: success or failure?
AB  - Despite a success in reducing rabies deaths from almost 200 to less than 20
      annually, this may not be considered a success. More than 400,000 persons
      required rabies post-exposure prophylaxis (PEP) in 2003, more than 4 times as
      many as those in 1991 [93,641 cases in 1991; 183,815 in 1996 and 350,535 in
      2001]. The number of samples submitted for testing in rabies diagnostic
      laboratories has been declining. However, the percent of samples that were
      confirmed infected with rabies during the 10 year period remained unchanged;
      within a range of 23 - 30% (MOPH report). Of the 6 million dogs roughly estimated
      to live in Thailand, there are no reliable data indicating their relative
      population densities or distribution patterns in various regions throughout the
      country. However, in a survey conducted by the Bureau of National Statistics and
      the Bangkok Metropolitan Administration in 1999, it was estimated that
      approximately 630,000 dogs dwell in Bangkok city (an area of 1 565 sq km). In
      this survey, approximately 110,000 of the dogs living in Bangkok were considered
      to be ownerless (stray or feral), whereas the remainder was believed to be owned
      or were community dogs. Nevertheless, it has not been known how many of the
      latter group can be accessible or are in compliance with local rabies control
      regulations. When the dog population statistics collected in 1999 are compared to
      an earlier survey conducted in 1992, the stray dog population appears to have
      almost tripled in size in Bangkok over the eight year

PMID- 15960232
TI  - Internet medical health ethics.

PMID- 15960233
TI  - NeuroAIDS research in resource-limited countries. Emerging priorities of the U.S.
      National Institute of Mental Health and the National Institute of Neurological
      Disorders and Stroke.

PMID- 15960234
TI  - NeuroAIDS in the developing world.

PMID- 15960235
TI  - Assessment of neuroAIDS in Africa.

PMID- 15960236
TI  - Neurological manifestations of HIV infection in Kwazulu-Natal South Africa.
AB  - South Africa has one of the fastest growing HIV epidemics in the world and
      KwaZulu-Natal, one of its nine provinces, is the epicentre of the epidemic. Of
      the estimated 5.3 million people infected with HIV in South Africa, 1.2 million
      reside in KwaZulu-Natal. Transmission of HIV is almost exclusively heterosexual,
      intravenous drug misuse does not occur and the patients attending state hospitals
      are antiretroviral drug naive. The neurological complications of HIV infection
      include bacterial and fungal meningitis, intracranial mass lesions, acute
      disseminated encephalomyelitis, a variety of spinal cord disorders, and
      peripheral nerve dysfunction. Tuberculous meningitis, especially that due to
      multidrug resistant organisms has a high mortality rate. Toxoplasmosis is the
      most frequent cause of intracranial mass lesions. These cases are successfully
      treated with cotrimoxazole alone. Multiple bacterial abscesses and tuberculomata
      are other important causes whilst primary central nervous system lymphoma is
      rare. The spinal cord disorders include co-infection with HTLV-I, tuberculosis
      and syphilis. Intramedullary tuberculomata, often multiple, and spinal epidural
      tuberculous abscess without bony disease are seen more commonly than in the pre
      HIV era. Peripheral nerve dysfunction include Gillian Barre Syndrome, chronic
      inflammatory demyelinating polyneuropathy and mononeuritis multiplex. Until the
      antiretroviral therapy roll out programme is well established the above HIV
      related neurological complications will continue to be seen for several years.

PMID- 15960237
TI  - Patterns of neuroAIDS in Africa.
AB  - According to UNAIDS, the African population accounts for greater than half of
      persons infected with HIV. Nevertheless, little information exists characterizing
      HIV in this population. Thus, the natural history and progression of HIV in the
      African population is virtually undocumented and therefore, poorly understood.
      Information regarding virtually every aspect of the disease including
      microbiology, pathogenicity, virulence, and clinical manifestation is based
      largely on data from select and limited populations. During the HAART-era, we
      have seen dramatic and significant changes in patterns of NeuroAIDS in patients
      in clinical cohorts from the United States and Western Europe. These observations
      have led to increased understanding of the progression of NeuroAIDS and have
      improved our ability to design treatment regimens to combat CNS complications
      resulting from HIV. Despite the existence of antiretroviral therapy for HIV, its
      absence in Africa along with poor treatments for opportunistic infections
      associated with HIV have become the main sources of neurological morbidity and
      mortality. In this context, we are presented with a unique opportunity to
      cultivate and enhance our understanding of the natural history and progression of
      NeuroAIDS in the African population thereby, better equipping healthcare
      providers, patients and their families in addressing this epidemic. This concept
      is particularly important as rapidly improving and more accessible anti-HIV
      medications and medications for the treatment of opportunistic infections become
      available to third world countries such as Africa. We believe that it is
      imperative to foster research, education and training between institutions in the
      industrialized world and Africa to close the gap in understanding patterns of
      NeuroAIDS in Africa.

PMID- 15960238
TI  - Simian immunodeficiency viruses (SIVs) in Africa.

PMID- 15960239
TI  - The manifestation of AIDS in Africa: an epidemiological overview.
AB  - The HIV epidemic in Africa has changed over the last decade and the incidence of
      AIDS, which was very low at the beginning of nineties, is now dramatically
      increasing. In this paper, we analyze the current situation of AIDS epidemiology
      on the continent, based on data generated by the antenatal care surveillance
      systems. As described here, the spread and prevalence of HIV differ in each
      African country, with South Africa now facing the worst situation. In addition,
      we have focused our attention on the modes and risks of viral transmission,
      highlighting the spread of HIV in particular subpopulations, which, for different
      reasons, prove to be more affected by the epidemic, such as sex workers and
      children. Genotype evolution and distribution in the various geographical areas
      are also considered. From this brief overview, it appears clear that poverty, the
      lack of technologies and inadequate resources, due mostly to social and economic
      instability, are widening the already existent gap between Africa and
      industrialized countries.

PMID- 15960240
TI  - Risk factors for human immunodeficiency virus type-1 acquisition in women in
      Africa.
AB  - Over 65% of individuals infected with human immunodeficiency virus type 1 (HIV-1)
      reside in sub-Saharan Africa, and thus efforts to change the course of the HIV-1
      pandemic should focus on this geographic region. Here, we discuss factors,
      including sexually transmitted diseases and hormonal contraceptive use, that
      impact susceptibility to HIV-1 in women in sub-Saharan Africa. This population is
      of special interest, given that women in this region are more likely to be
      infected than men. In addition, they are a potential source of transmission to
      their infants. A better understanding of the factors that influence HIV-1
      susceptibility is key to developing interventions to control the epidemic.

PMID- 15960241
TI  - Antiretroviral therapy in the developing world.

PMID- 15960242
TI  - They drink the wine of violence.

PMID- 15960243
TI  - Disseminating nursing knowledge--a guide to writing for publication.
AB  - The dissemination of research findings and other forms of nursing knowledge is
      generally accepted as an element of accountability for professional practice.
      While an increase in nursing research has been apparent in recent times, there
      seemingly remains a reluctance for nurses to publish the findings of their work.
      The identified barriers to writing for publication primarily focus on a lack of
      confidence in the ability to write in this arena, and uncertainty, apprehension
      and confusion regarding how exactly to go about writing and submitting a
      manuscript. The primary aim of this paper is to demystify the process of writing
      for publication by presenting a guide ranging from selecting the journal, to
      dealing with the reviewers' comments. Although the available literature includes
      a number of helpful hints, coverage of all of the relevant aspects in one article
      could not be located. It is intended that this paper will provide a valuable
      contribution by encouraging nurses to develop their research findings or other
      scholarly ideas into a manuscript to be submitted for publication.

PMID- 15960244
TI  - Back to the future: making a case for including the history of mental health
      nursing in nurse education programmes.
AB  - Reflections on nursing history, the nature of its workforce and its evolution as
      a profession can be powerful tools in the development of professional identity.
      Historical accounts of mental health nurses' practice and how they are socially,
      politically and culturally positioned within a particular time frame serve to
      illustrate that as practitioners we are precariously placed within a certain
      point in history. This paper emphasises the importance of mental health nursing
      historical research within nurse education curricula as a means of situating
      current theories, practice and professional identity. It further proposes that as
      today's practice becomes tomorrow's history, mental health nursing will continue
      to respond in a dynamic way to the practices and policies of the day.

PMID- 15960245
TI  - Psychiatric nurses and undergraduate nursing students' perceptions of
      preceptorship in the mental health setting.
AB  - The importance of clinical education for nursing is widely acknowledged and
      considerable effort has been invested into identifying the most effective models.
      Psychiatric nursing has the additional imperative of increasing recruitment into
      the field. While clinical experience has been found to influence nursing
      students' attitudes towards psychiatric nursing and people experiencing a mental
      illness, little attention has been paid towards the factors that influence these
      outcomes. This study addresses the question, what is the experience of
      preceptorship for mental health nurses and undergraduate nursing students' in the
      mental health setting? An examination of the interactions within this model and
      the development of a substantive theory are facilitated by utilising the
      qualitative methodological approach, grounded theory. Findings indicate that
      psychiatric nurse preceptors seek to accomplish connectedness in the
      preceptorship relationship, through overcoming fear and other misconceptions. In
      addition, a number of factors emerged where commonality exists between the
      experiences of mental health nurse preceptors andthe nursing students. These
      included the need to manage the reconciling of difference between general acute
      health and mental health settings, the challenge for both groups to address
      student fear and preconceived ideas of mental illness and the need of preceptors
      to 'protect' the students.

PMID- 15960246
TI  - Caregiver coping in dementing illness--implications for short-term respite care.
AB  - The increasing cost of caring for older people with dementia is just one of two
      key justifications for researching service interventions designed to help sustain
      dementia sufferers within their own home. Secondly, studies consistently
      highlight an almost universal determination by spouse caregivers to avoid
      institutionalisation by coping to the 'bitter end' or at least until their coping
      resources have been irrevocably depleted (Knight et al, 1993; Barnes et al, 1981;
      Upton, 2001). The experience of coping with a dementing spouse is known to be
      enduring, stressful and pathogenic to the caregiver (Schwarz and Blixen, 1997;
      Rosenheimer and Francis, 1992). Many carers describe short periods of personal
      private time and space away from the psycho-physiological demands of caregiving
      as therapeutic coping facilitators. The term 'respite care' (essentially a
      professional colloquialism) is a multi-agency response to the needs of such
      carers and typically refers to a range of interventions from befriending/sitting
      services; day-care services; to short-term residential/in-patient care. This
      paper, taken from a PhD study into the day-to-day coping experience of forty-six
      spouse carers (Upton, 2001), explores the issue of coping and its respite
      implications for day and short-term residential/in-patient care. The high status
      of the respite concept as coping enhancer is highlighted along with the dangers
      of using an intervention, which can paradoxically accelerate expensive, unwanted
      and primarily unnecessary long-term care placement.

PMID- 15960247
TI  - Techniques for immediate loading in extraction and grafted sites.

PMID- 15960248
TI  - Impostors targeting U.S. hospitals: could terrorists come to your ED?
AB  - Be aware of tactics commonly used by impostors, and make sure your department is
      prepared. Impostors may claim to be accreditation surveyors, health care
      professionals, or even government agents. Be alert to vehicles loitering near
      your entrance or slowly driving around your facility. Ask friends and family
      members to make late-night visits to evaluate how easily visitors can access your
      department.

PMID- 15960249
TI  - Adapt use of physician extenders for your needs.
AB  - Know the scope of practice for all physician extenders--not only for those who
      work solely in your department but for other hospital specialties. The Joint
      Commission on Accreditation of Healthcare Organizations requires you explicitly
      follow the bylaws of your medical staff concerning allied practitioners. You can
      create a more limited scope of practice than outlined by the state but not a more
      expansive one. Make sure a mechanism is in place for checking the privileges of
      extenders in the ED who come from other departments.

PMID- 15960250
TI  - New ambulance policy slashes diversion hours.
AB  - Focus on practitioners' needs to develop a diversion plan that makes sense and
      will be effective. Directing patients to the right facility will eliminate
      duplication of efforts on histories and tests. Limit the amount of time a
      hospital's ED can be on diversion before it must again accept ambulance patients.
      Tracking the performance of EDs creates pressure to adhere to requirements of
      program.

PMID- 15960251
TI  - Can't ID a difficult rash? Digital photos can help.
AB  - Using a software program with vivid illustrations can help your staff make
      difficult diagnoses of rashes. Some medical texts have no illustrations at all.
      Digital photos have much more clarity than traditional pictures. Encourage your
      staff to use diagnostic software as an educational tool. Use hypothetical cases.
      Train key individuals in use of software and have them train the rest of the
      staff.

PMID- 15960252
TI  - [Comment on some spinal surgery].
AB  - Bone tumor metastases is relatively common. Approximately 5%-20% of spinal
      metastatic tumors will finally invade the spinal cord and exacerbate symptoms.
      The adoption of combined approach in recent years has significantly increased the
      survival rate. After excision of the tumors, internal fixation instrumentations
      are needed to stabilize the vertebrae. These procedures must be performed under
      the condition that the patients can tolerate the operation. Fused vertebra with
      instrumentation may cause degenerative diseases at the adjacent segments, which
      has been a problem of concern recently. Results of biomechanical tests indicated
      that these degenerative changes are related to the increased motion range of the
      neighboring segments. An old view is "the more rigid the instrumentation is, the
      better the results are", which has been disproved by clinical evidences. Improper
      use of internal spine fixation instrument should be avoided. Artificial
      intervertebral disc replacement can produce favorable short-time effects,
      however, its long-term effects and complications still requires further
      observations.

PMID- 15960253
TI  - [Expression of collagen type I in the articular processes of apex from adolescent
      idiopathic scoliosis patients].
AB  - OBJECTIVE: To investigate the characteristic of the expression of collagen type I
      in the articular processes of apex from adolescent idiopathic scoliosis (AIS)
      patients. METHODS: The apical processes of 11 AIS patients were collected. The
      techniques of HE staining and In-cell Western were adopted in this research. We
      studied the pathological changes of the apical processes and collected and
      cultured the osteoblast from the apical processes on both sides in vitro
      separately. After cell identification, we compared the secretion of collagen type
      I in the osteoblast from concave side to that of convex side. RESULTS: The
      cartilages of the apical processes showed some signs of regression. The secretion
      of collagen type I of the osteoblast in vitro from the concave side of the apical
      articular process was significantly higher than that from the convex side (P <
      0.05). CONCLUSION: Significant difference of the gene expression of the
      osteoblasts from the apical process exists between the concave side and the
      convex side.

PMID- 15960254
TI  - [Repair of acute spinal cord injury promoted by transplantation of olfactory
      ensheathing glia].
AB  - OBJECTIVES: To observe olfactory ensheathing glia (OEG) survival and repair in
      vivo for spinal cord injury after OEG transplantation. METHODS: The OEG was
      cultured with the olfactory bulb of Wistar neonate rats. The spinal cords
      contusion was made in group A, B, and C with the New York University impactor,
      then complete transection was performed in the contusion area in group A. OEG
      labeled by Hoechst was transplanted in group A and B. In group C, DMEM were
      injected. In group D, laminectomies were done without cord contusion and
      transection. The functional recovery of the spinal cord injury [Basso, Beattie,
      Bresnahan (BBB) Locomotor Rating Scale scores] and changes of body weight were
      observed. The tissue sections were done 24 weeks postoperatively. HE staining,
      neurofibril (NF) immunohistochemical staining, and silver staining were performed
      respectively to observe the pathologic changes and axon regeneration. The
      survival of OEG labeled by Hoechst was observed under the fluorescence
      microscope. RESULTS: Locomotive behaviour improved 4 weeks postoperatively. The
      BBB locomotion scores of group A and B were significantly higher than that of
      group C in all periods (from 4 weeks to 24 weeks) (P < 0.01). Sixteen weeks after
      operation, the BBB locomotion scores became stable and showed no change. HE
      staining showed that the area of spinal cord injury was disorder and the number
      of nerve cell was more in group A and B. In group C, there was the obvious cavum
      and few wring nerve fiber in the area of spinal cord injury. The nerve fibers
      innervated to the injuried area in group A and B were more than that of group C,
      but less than that of group D. A great number of OEG labeled by Hoechst were
      observed around spinal injuried area under fluorescence microscope. After
      operation, the body weight reduced in every group. The body weight of group D had
      recovered after 2 weeks and gradully increased. After 4 weeks, the body weight in
      group A, B, and C decreased to the minimum and were significantly less than that
      of group D (P < 0.01). After this, body weight in group A and B increased and was
      significantly more than that of group C (P < 0.05). CONCLUSIONS: OEG
      transplantation can promote the axons regeneration and the recovery of locomotion
      function in experimental spinal cord injuries.

PMID- 15960255
TI  - [Anterior and posterior spinal growth plates in adolescent idiopathic scoliosis:
      a histological study].
AB  - OBJECTIVE: To investigate the morphology of the growth plates in anterior and
      posterior spinal column in adolescent idiopathic scoliosis (AIS) and congenital
      scoliosis (CS) respectively. METHODS: Seventeen AIS patients (mean age 13.6
      years, ranged 10 to 17 years) were recruited in this study and 10 patients with
      CS (mean age 9.3 years, ranged 6 to 12 years) were selected as control group.
      Growth plates were harvested during anterior and posterior surgery and then were
      paraffin embedded, sectioned at the thickness of 6 microm, and stained with
      Heametoxylin and Eosin. Quantitative histomorphometric analysis was made to
      measure the area and height of proliferative and hypertrophic zones by image
      analysis system. RESULTS: In AIS, the hypertrophic and proliferative zones were
      significantly larger and/or higher in anterior column than those in posterior
      column (P < 0.05). The sizes of different subtype zones were similar in anterior
      and posterior columns in CS. CONCLUSION: The histological difference between
      anterior and posterior spinal column may exist in patients with AIS. The
      overgrowth of the anterior spinal column may predispose to lordotic instability
      and development of spine deformity.

PMID- 15960256
TI  - [Biomechanical evaluation of stiffness of long-segment instrumented spine].
AB  - OBJECTIVE: To test the changes of the stiffness of the intact, released, and
      instrumented spines in an in vitro porcine model. METHODS: Twelve porcine spines
      (12 segments each) were harvested for the biomechanical tests with Material Test
      System. Stiffness during flexion, extension, lateral bending, and axial rotation
      were recorded; then the specimen was released with intervertebral discs and the
      facet joints removed, followed by repeating the biomechanical tests for
      stiffness; and finally, a double-rod titanium construct was applied for internal
      fixation to each released spine and stiffness tests were repeated again. RESULTS:
      Compared with the intact porcine spines [stiffness during flexion, extension,
      lateral bending, and axial rotation was 52.89 +/- 15.98, 105.43 +/- 56.38, 42.09
      +/- 14.73, and (16.94 +/- 4.85) N x mm/degrees, respectively], the stiffness of
      the released porcine spines [stiffness during flexion, extension, lateral
      bending, and axial rotation was 44.04 +/- 13.73, 41.46 +/- 10.80, 31.75 +/- 7.23,
      and (9.10 +/- 2.07)N x mm/degrees, respectively] significantly decreased (P <
      0.05), while significantly increased stiffness was found in the instrumented
      porcine spines [stiffness during flexion, extension, lateral bending, and axial
      rotation was 385.96 +/- 143.25, 138.96 +/- 59.41, 152.56 +/- 87.15, and (55.91 +/
      16.49) N x mm/degrees, respectively] (P < 0.05). CONCLUSION: Higher instant
      stiffness was found in instrumented spine than the intact one during flexion,
      extension, lateral bending and axial rotation.

PMID- 15960257
TI  - [Design and experiment of the pedicle aiming device for the cervical spine].
AB  - OBJECTIVE: To probe the accuracy and safety of using an aiming device in the
      transpedicular fixation of cervical spine. METHODS: Eight cervical specimens were
      obtained. We used the computed tomography (CT) to scan C3 to C7, measured the
      medial angle of the pedicle, and determined the location of the pedicle
      projecting on the articular process. Then we took the oblique X-ray film,
      measured the cephalic/caudal angle of the pedicle, and determined the location of
      the pedicle projecting on the articular process. All the specimens were equally
      divided into two groups. Screws of 2.8 mm x 30 mm, were used. Specimens in one
      group were inserted with the transpedicular screw manually, while specimens in
      the other one inserted with the transpedicular screw using a self-designed aiming
      device that can be modulate at the three dimensions according to the angles of
      the pedicles. RESULTS: The first group totally had 40 screws from C3 to C7. There
      were 13 screws in the pedicle, 9 violated the walls of the pedicle but not
      involved the adjunct structure, and 18 injured the important structure such as
      spinal cord, verteberal artery, or nerve root. In the other group, only 4 screws
      violated the walls of the pedicle but not involved the adjunct structure, and the
      others all in the pedicles. The difference was of statistical significance (P <
      0.01). CONCLUSION: In the cervical spine, transpedicular fixation using an aiming
      device can improve the accuracy and safety during operation.

PMID- 15960258
TI  - [Reoperative treatment of lumbar disc herniation].
AB  - OBJECTIVE: To explore the causes, methods and outcomes of reoperative treatment
      after lumbar disc surgery. METHODS: Nine hundred and twenty eight patients with
      lumbar disc herniation were treated surgically from January 1995 to January 2004,
      of whom 43 patients (4.6%) underwent reoperation due to persistent pain or
      recurrence of symptoms. Forty patients were followed up from 3 months to 84
      months (mean 30 months). RESULTS: According to Macnab's criteria, outcomes were
      excellent in 11 cases (27.5%), good in 16 cases (40%), fair in 8 cases (20%), and
      poor in 5 cases (12.5%). CONCLUSIONS: The major causes of reoperation after
      lumbar disc surgery included incomplete removal of herniating discs and recurrent
      disc herniation of primary interspace, secondary lumbar canal stenosis, and
      adhesion of nerve roots. Prior to primary surgical treatment of lumbar disc
      herniation, operative indications must be strictly accurate, surgical methods
      should be correctly selected, and improved and refined surgical skills should be
      guaranteed. Satisfactory outcomes can be gained with reoperation for patients who
      still requiring treatment.

PMID- 15960259
TI  - [Surgical treatment and its related factors of cervical spondylotic myelopathy].
AB  - OBJECTIVE: To observe the results and its related factors of surgical treatment
      of cervical spondylotic myelopathy (CSM). METHODS: Totally 365 CSM patients were
      reviewed. All patients were treated with anterior cervical decompression and
      fusion with autogenous iliac bone or titanium mesh cages with local bone graft.
      Anterior locking plates were used for fixation. Five patients received revision
      surgery 3 to 6 months after the initial operation. RESULTS: Clinical function was
      excellent in 175 patients (47.94%), good in 129 patients (35.34%), fair in 44
      patients (12.05%), and poor in 17 patients (4.66%). CONCLUSION: Anterior cervical
      decompresion of CSM has good clinical efficacy. The timing of operation, disease
      severity, and surgical technique are the important factors affecting the outcome
      of treatment.

PMID- 15960260
TI  - [Characteristics of nerve root compression caused by degenerative lumbar stenosis
      with scoliosis].
AB  - OBJECTIVE: To investigate the factors that may contribute to radiculopathy in
      degenerative lumbar stenosis with scoliosis (DLSS) and their association with the
      pattern of the scoliosis. METHODS: Twenty-seven patients with DLSS were examined
      in our hospital. The symptomatic nerve roots were determined by pain
      distribution, and neurological findings. The compressive factors were diagnosed
      by magnetic resonance imaging and myelography or radiculography. The pattern of
      scoliosis was determined by plain radiographs. Correlation between the affected
      nerve root and the compressive factors or the pattern of the scoliosis were then
      analyzed. RESULTS: Among the 27 patients, L3 root was affected in 6 patients, L4
      root in 13 patients, L5 root in 15 patients, and S1 root in 9 patients. L3 and L4
      roots were more compressed by foraminal or extraforaminal stenosis on the concave
      side of the curve, whereas L5 and S1 roots were commonly affected by lateral
      recess stenosis on the convex side. CONCLUSION: In DLSS, nerve root compression
      is not only seen on the concave side of the scoliosis, but also equally involved
      on the convex side. Most radiculopathy in DLSS distributes close to central
      sacral vertical line, which may be due to the abnormal weight-bearing for the
      pattern of scoliosis.

PMID- 15960261
TI  - [Selectivity and individualization of transpedicular balloon kyphoplasty for aged
      osteoporotic spinal fractures].
AB  - OBJECTIVE: To investigate the selectivity and individualization of transpedicular
      balloon kyphoplasty for aged osteoporotic spinal fracture. METHODS: Twenty-two
      consecutive procedures were performed in 17 aged patients with osteoporotic
      spinal compression fractures from April 2002 to June 2004. The signal changes in
      different sequences were confirmed by magnetic resonance imaging before the
      procedures. This operation involved the percutaneous insertion of two inflatable
      bone tamps into a fractured vertebral body transpedicularly under fluoroscopic
      guidance. Every patient was treated individually, according to the results of
      radiography and CT scan before operation. Preoperative and postoperative
      complications, visual analogue scale, and radiographic findings such as vertebral
      height and Cobb angle were recorded and analyzed. RESULTS: All patients tolerated
      the procedure well with immediate relief of their back pain in 24 hours. There
      was no leakage of cement into the epidura. The mean loss percent of the anterior
      and middle vertebral heights were (35.32 +/- 13.15)% and (27.53 +/- 12.61)%
      before operation, and (14.21 +/- 12.43)% and (16.2 +/- 7.5)% after operation. The
      height restoration of vertebra was confirmed by X-ray after the procedure (P <
      0.01). The mean kyphosis was improved from (25.3 +/- 4.2) degrees to (8.6 +/-
      5.1) degrees. No complications occurred. No patient had nerve injury. The
      patients were allowed to walk next day after the procedure. CONCLUSION: The
      selectivity and individualization of transpedicular balloon kyphoplasty for aged
      osteoporotic spinal fractures has satisfactory short-term clinical efficacy. It
      is also an effective way to prevent complications.

PMID- 15960262
TI  - [Surgical treatment of metastatic spinal tumors by anterial approach].
AB  - OBJECTIVE: To investigate the efficacy of surgical treatment of the patients with
      metastatic spinal tumors by anterial decompression and stabilization. METHODS:
      From December 1997 to December 2003, 93 patients (40 women and 53 men) with
      metastatic spinal tumors were treated in our department. The locations of the
      tumor included, thoracic vertebra (53 cases), lumbar vertebra (33 cases), and
      cervical region (7 cases). The original tumors included lung cancer (21 cases),
      renal cancer (13 cases), prostate cancer (8 cases), hepatic cancer (5 cases),
      breast cancer (13 cases), thyroid cancer (5 cases), gastrointestinal tumor (3
      cases), and multiple myeloma (8 cases). However, no primary tumor was found in
      the rest of 17 cases. Among 54 of 93 patients who presented with neurological
      dysfunction, 16 patients completely paralyzed and others incompletely paralyzed.
      The follow-up time ranged from 10 to 72 months. RESULTS: Pain was relieved in 87
      of 93 patients (93.5%) and neurological function was improved in 47 of the 54
      patients. Among 16 completely paralyzed patients, 7 patients experienced a
      neurological function improvement (from Frankel grade A or B to C or D after
      decompression). The average amount of blood transfused was 3000 ml. No severe
      complications were seen in our series. The one-year survival rate was 85% (79
      cases). CONCLUSIONS: The integrity of the spinal column structure and
      neurological function should be considered firstly in the treatment of spinal
      metastasis. Thorough resection of metastatic tumor and stable internal fixation
      by anterior approach should be performed when single or two vertebra are
      involved. In order to alleviate paralysis, promote spinal stability, and improve
      the quality of life, urgent decompression should be performed on patient with
      spinal metastasis.

PMID- 15960263
TI  - [Repairing segmental radial bone defect with poly (3-hydroxybutyrate-co-3
      hydroxyvalerate)/sol-gel bioactive glass composite porous scaffold].
AB  - OBJECTIVE: To investigate the capability of the bone regeneration of poly (3
      hydroxybutyrate-co-3-hydroxyvalerate/sol-gel bioactive glass (PHBV/SGBG)
      composite porous scaffold. METHODS: PHBV/ SGBG composite porous scaffold was
      implanted into the segmental radial bone defect of the New Zealand white rabbits,
      PHBV/hydroxylapatite (PHBV/HA) as experimental control. The degradability,
      biocompatibility, and bone regeneration capability of the implants were evaluated
      through radiological, histological, computerized graphic, and biomechanical
      analysis. RESULTS: The new bone formation occurred as early as 4 weeks after
      implantation of PHBV/SGBG composite porous scaffold. The defect was filled with
      new bone 8 weeks after the implantation, and was completely repaired 12 weeks
      after operation. The new bone had normal bone structure and the medullar cavity
      regenerated. The biomechanical study showed that the anti-compression force of
      radial specimen in PHBV/SGBG groups was significantly higher than in PHBV/ HA
      groups (P < 0.05), but no significant difference existed between PHBV/SGBG group
      and autograft bone group (P>0.05). The PHBV/SGBG composite porous scaffold
      degraded no sooner than 4 weeks after the implantation and most of scaffold was
      absorbed after 12 weeks. The proportion of the scaffold to new bone decreased
      from 60% by week 4 to 8% by week 12. CONCLUSIONS: PHBV/SGBG composite porous
      scaffold is a degradable bone substitute. It can achieve early bone generation
      and complete repair. It can be used as an ideal scaffold for tissue-engineering
      bone.

PMID- 15960264
TI  - [Endovascular microcoil applied for gene delivery system].
AB  - OBJECTIVE: To explore the possibility of using an endovascular microcoil as a
      gene delivery system. METHODS: Anti-adenoviral monoclonal antibodies were
      covalently attached to the collagen-coated surface of platinum microcoil. These
      antibodies were used to tether adenovirus encoding green fluorescent protein (Ad
      GFP). Cell culture studies with rat arterial smooth muscle cells (A10) assessed
      transduction on or near the coil. Platinum coils coated with Ad-GFP were
      implanted into the ligated common carotid artery (CCA) of adult rats in a model
      of arterial stasis and pressurization. After 7 days, CCA segments were harvested,
      and coils were removed for histopathology and GFP expression studies, while
      organs were evaluated by polymerase chain reaction to assess viral
      biodistribution. RESULTS: In cell culture studies, GFP-positive smooth muscle
      cells were detected only on the platinum coil surface. After 7 days, GFP was
      detected on the harvested platinum coil and in the organizing thrombus within the
      CCA according to fluorescence microscopy and immunohistochemistry. Morphometric
      analyses revealed that (13.3 +/- 2.0)% of cells within the organized thrombus
      were transduced with Ad-GFP via the gene delivery system. Ad-GFP was not
      detectable by polymerase chain reaction in lung, liver, or kidney. CONCLUSIONS:
      Gene delivery endovascular microcoils represents an interventional device-based
      gene therapy system that can serve as a suitable platform for either single or
      multiple gene therapy vectors.

PMID- 15960265
TI  - [Cloning and characterization of a novel mouse aging-related gene Arzc].
AB  - OBJECTIVE: To clone and identify novel mouse aging-related genes. METHODS: The
      improved differential display reverse transcription-polymerase chain reaction
      method was used to analyze the differential expression of old and young BALB/C
      mouse cortex tissues. The novel expression sequence targets (EST) with
      differential expression were further confirmed by Northern blot and used as
      original sequence to clone the full-length cDNA sequence by bioinformatics
      technique. The reverse transcription products of BALB/C mouse cortex total RNA
      was used as the amplification template. RESULTS: A total of 42 differentially
      expressed EST were obtained. Homologic analysis showed that 29 EST represented
      known cDNAs and 13 were probably new EST. One of the EST, which were confirmed to
      have down regulative expression in the old mouse cortex tissues by Northern blot
      analysis, was used to obtain the full-length cDNA sequences from reverse
      transcription products of total RNA of BALB/C mice cortex by bioinformation
      method. A 1 382 bp of cDNA sequence including the EST was obtained and designed
      as Arzc (GenBank accession number: AY344585). The Arzc cDNA contains an open
      reading frame of 261 bp and encodes a peptide of 86 amino acids residuals. FASTA
      analysis showed that the deduced peptide had a homology with a portion of
      integrase/recombinase, a member of a phage integrase family. CONCLUSION: A novel
      mouse gene that is probably related to aging was identified and cloned.

PMID- 15960266
TI  - [In vitro expansion of cord blood megakaryocyte progenitor].
AB  - OBJECTIVE: To expand cord blood megakaryocyte progenitor cells in vitro. METHODS:
      Cord blood CD34+ cells were selected by magnetic cell sorting (MACS), and
      thrombopoietin (TPO), interleukin-11 (IL-11), and heparin were used in the
      expansion system of megakaryocyte progenitor. The expansion efficiency was
      measured by fluorescence-activated cell sorting (FACS) using the megakaryocytic
      specific monoclonal antibodies (CD34+, CD41a+, CD61+, CD34+CD41a+, CD41a+CD61+)
      and colony-forming units-megakaryocyte (CFU-MK) analysis. The expanded
      megakaryocyte progenitor were determined by histochemistry staining using CD41a
      and the observation of the ultrastructure of megakaryocyte (MK) by electron
      microscopy. The megakaryocyte function were examined by the platelet activation
      in vitro and nonobese diabetic/severe combined immunodifficiency (NOD/SCID) mice
      transplantation in vivo. RESULTS: CD34+CD41a+ cells was expanded (4.0 +/- 1.7)
      folds on day 7 in TPO (50 ng/ml) group and (10.5 +/- 4.8) fold in TPO combined
      with IL-11 group; after heparin was joined in on day 0, a more significantly
      elevated expansion was found in the heparin, TPO, and IL-11 group [(29.9 +/- 6.4)
      folds than the above two groups; P < 0.05]. Meanwhile, the large CFU-MK colony (>
      50 cells/colony) was (106.8 +/- 26.9) folds on day 7 (P < 0.05). The
      megakaryocyte expanding with TPO, IL-11 and heparin for 7 days in vitro
      transplanted the NOD/SCID mice fasten the recovery of platelet and white blood
      cell account and improved the survival. Megakaryocyte under culture displayed
      certain development of territories membrane. Platelet activation test comfirmed
      that the expanding megakaryocyte progenitor had the normal function. CONCLUSION:
      TPO, IL-11, and heparin combination system for ex vivo expansion is an effective
      expansion system of megakaryocyte progenitor.

PMID- 15960267
TI  - [Dipeptidyl peptidase IV gene expression in ovarian carcinoma cell lines with
      various maligant behaviour].
AB  - OBJECTIVE: To study the relationship between the expression of dipeptidyl
      peptidase IV (DPP IV) gene and malignant behavior of cells of ovarian carcinoma.
      METHODS: The differences of the malignant behavior of A2780, SKOV-3, HO-8910 and
      HO-8910PM cell lines were examined by drawing cell proliferative curves, adhesive
      test, assay of incursion and chemotaxis. The expression of DPP IV among the cell
      lines and its relationship with the malignant behavior of ovarian carcinoma cell
      were detected by techniques of DPP IV activity assay, cytometry and reverse
      transcription polymerase chain reaction. RESULTS: Among all cell lines, the
      ability of proliferation, adhesion, incursion and chemotaxis of HO-8910PM were
      the highest, while those of A2780 were the lowest. The transcription of mRNA in
      A2780, SKOV-3, HO-8910 and HO-8910PM cell lines were 0.7512 +/- 0.0012, 0.5596 +/
      0.0015, 0.3369 +/- 0.0009, and 0.2777 +/- 0.0006, respectively. The activity of
      DPP IV were 0.79 +/- 0.02, 0.64 +/- 0.03, 0.21 +/- 0.02, and 0.18 +/- 0.01,
      respectively; and the protein expression of DPP IV gene were 657.83 +/- 1.14,
      538.53 +/- 5.29, 130.50 +/- 1.46, and 33.14 +/- 0.47, respectively, as assayed by
      cytometry. The correlation coefficients of the transcription of DPP IV gene and
      the adhesive, incursive and migratory ability of ovarian carcinoma cells were 
      0.987, -0.983, and -0.991, respectively; the correlation coefficients of the
      expression of DPP IV and those ability of cells were -0.959, -0.988, and -0.968;
      the correlation coefficients of the activity of DPP IV and those ability of cells
      were -0.952, -0.868, and -0.983. CONCLUSION: There is a negative correlation
      between the expression of DPP IV gene and the adhesive and incursive capability
      of cells of ovarian carcinoma.

PMID- 15960268
TI  - [Inhibition of multidrug resistance gene 1 expression in glioma by antisense
      oligodeoxynucleotides].
AB  - OBJECTIVE: To investigate the effectiveness of phosphorothioate multidrug
      resistance gene 1 (MDR1) antisense oligodeoxynucleotides (MDR1-AS) suppressing
      MDR1 expression in multidrug-resistant glioma cell line C6/adr. METHODS: The
      glioma cell line C6/adr served as the tested model in vitro, MDR1-AS (5'
      CTCCATCACCACCTC-3'), complementary to the -9- +6 sequence of first exon, was
      synthesized and phosphorothioate-modified. As control of sequence specificity,
      MDR1-S (5'-GAGGTGGTGA TGGAG-3') was used. Both antisense and sense
      oligodeoxynucleotides were transduced to C6/adr cells by lipofectin. The
      cytotoxity of MDR1-AS was tested using morphological observation and 3- (4,5
      dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide assay. Semi-quantitative
      reverse transcription polymerase chain reaction was used to monitor the
      expression levels of the MDR1 mRNA in the different groups. The positive rate of
      the MDR1 gene product P glycoprotein (P-gp) was determined by flow cytometry
      assessment. RESULTS: No cytotoxicity of MDR1-AS was observed. The MDR1 mRNA
      expression level was decreased from 106% to about 30.44% 48 h after MDR1-AS
      treatment. The P-gp positive rate of MDR1-AS treated C6/adr cells decreased from
      100% to 32.77%, with that of C6/adr cells considered as 100%. CONCLUSIONS: MDR1
      AS can effectively inhibit MDR1 expression in the C6/adr cell line at both the
      mRNA and protein level, and may be an alternative treatment of drug-resistant
      gliomas.

PMID- 15960269
TI  - [Protective efficacy of recombinant rotavirus epitope-based vaccine in mice].
AB  - OBJECTIVE: To evaluate in vivo immunological protective efficacy and safety of
      expressed recombinant rotavirus epitopes in mice. METHODS: Using the Flock House
      virus capsid protein as a vector, three epitopes derived from rotavirus Vp4 amino
      acid 223-242 [rotavirus epitope A, (REA)], 243-262 [rotavirus epitope B, (REB)],
      and 234-251 [rotavirus epitope C, (REC)] were genetically engineered on the
      surface of the vector protein and expressed in pET-3 (E. coli BL21 [DE3]) system
      into multiple epitopes, REABC, which comprises REA, REB, and REC. Kunming strain
      mice were inoculated with the recombinant epitopes REABC, and then challenged
      perorally by cell culture-adapted rotavirus Wa (type G1P1A) and SA11 (type G3P2).
      Infection syndrome was observed, and virus antigen in stools of mice and serum
      neutralizing antibody activities were determined and analyzed. RESULTS: The
      recombinant epitopes REABC significantly induced rotavirus specific neutralyzing
      antibodies against WA and SA11, reduced virus reproduction, elicitted immune
      memory in inoculated mice, and protected inoculated mice from challenge by WA or
      SA11 (P<0.001). CONCLUSION: The recombinant epitopes have high immunological
      protective efficacy and mild side effects in mice. It may be used as an epitope
      based vaccine candidate in human.

PMID- 15960270
TI  - [Effects of naloxone on glutamate release in combined oxygen-glucose deprivation
      of primary cultured human embryo neuron].
AB  - OBJECTIVE: To investigate the effects of naloxone on glutamate release in
      combined oxygen-glucose deprivation of primary cultured human embryo neurons.
      METHODS: The primary cultured embryonic human cortical neurons were demonstrated
      by immunocytochemical stain of neural filament (NF). The neurons were randomly
      allocated into control group, hypoxic group, and experimental group. The
      experimental group was further divided into three subgroups pretreated with
      different concentrations of naloxone (0.25, 5, 10 microg/ml). The neurons of
      hypoxic group and experimental group were deprived both oxygen and glucose for 1
      hours followed by 24 hours of reoxygenation. Meanwhile, we used 3-(4, 5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, high
      performance liquid chromatography (HPLC), and biological analysis to study the
      survival rate of neurons and the changes of extracellular glutamate and lactate
      dehydrogenase (LDH) levels after 24 hours of reoxygenation. RESULTS: One hour of
      oxygen-glucose deprivation followed by 24 hours of reoxygenation was associated
      with a large increase in extracellular LDH and glutamate and a significant
      decrease of cell vitality (P < 0.01). Naloxone exerted a concentration-dependent
      protection against neuronal injury provoked by combined oxygen-glucose
      deprivation. After reoxygenation, the extracellular concentrations of glutamate
      gradually decreased (P < 0.05, P < 0.01, respectively) and cell vitality
      increased (P < 0.01) with increase of the concentration of naloxone compared with
      control group. All of them returned to control level when naloxone was up to 10
      microg/ml (P > 0.05). CONCLUSION: Naloxone protects neurons from hypoxic injury
      by inhibiting the release of glutamate and therefore alleviating the exciting
      toxicity.

PMID- 15960271
TI  - [Combination of morphine with low-dose naloxone for intravenous patient
      controlled analgesia].
AB  - OBJECTIVE: To compare the analgesic effect and side effects of morphine for
      intravenous patient-controlled analgesia (PCA) with or without low-dose naloxone
      after abdominal surgery. METHODS: Fifty-nine ASA I - II patients undergoing
      elective abdominal surgery were randomly divided into two groups: group morphine
      received postoperative PCA with 0.4 mg/ml morphine (a 1 mg bolus with a 5 min
      lockout), group naloxone received morphine 0.4 mg/ml with 6 microg/kg naloxone.
      Blood pressure, heart rate, respiratory rate, and pulse oxygen saturation were
      monitored. Visual analogue scale (VAS), nausea/vomiting, pruritus, sedation and
      consumption of morphine were recorded for 24 hours. RESULTS: VAS had no
      difference between group morphine and group naloxone, but group naloxone had
      significantly lower VAS for pain at rest or movement (beyond 4-8 h), and the
      incidence of nausea/vomiting significantly decreased in group naloxone (P <
      0.05). No differences existed in pruritus, sedation, respiratory rate, and
      hemodynamic parameters between these two groups. The 24 hours postoperative
      morphine consumption was (36.6 +/- 13.5) mg in group naloxone and (43.7 +/- 14.6)
      mg in group morphine (P < 0.05). CONCLUSION: For morphine PCA, morphine with 6
      microg/kg naloxone is effective in preventing some PCA morphinerelated side
      effects. Naloxone not only reduces postoperative morphine requirements but also
      improves the analgesic effect.

PMID- 15960272
TI  - [Risk factors and prognosis of contrast-induced nephropathy with renal
      dysfunction].
AB  - OBJECTIVE: To investigate the risk factors, clinical characteristics, and
      prognosis of contrast-induced nephropathy (CIN) in patients with renal
      dysfunction. METHODS: We retrospectively analyzed 44 patients with renal
      dysfunction who received coronary angiography in our hospital. CIN was found in
      23 patients, after angiography. We compared the clinical characteristics,
      medication during angiography day, volume of contrast-medium, as well as renal
      function changes before and after angiography in patients with (23 cases) and
      without (21 cases) CIN. The CIN patients were further divided into two groups
      according to their serum creatinine (Scr) levels: renal function recovery group
      (12 cases) and renal function non-recovery group (11 cases), and difference
      between these two groups was analyzed. RESULTS: CIN incidence was 52.3% (23/44)
      in all 44 patients with renal dysfunction. CIN incidence was 42% (8/19) in
      patients whose Scr was between 132.6 - 168 micromol/L, was 60% (15/25) in those
      whose Scr was more than 176.8 micromol/L. In all 23 CIN patients, the average
      volume of contrast-medium was (144.79 +/- 71.8) ml, while 43.5% of the CIN
      patients whose dosage was over the maximum threshold of contrast-medium; the
      average risk factors were 5.14 +/- 1.3. Compared with the group without CIN, the
      difference was statistically significant (P < 0.05). Multiple stepwise regression
      analysis showed the volume of radio-contrast-medium was correlated with CIN in
      patients with renal dysfunction (F=10.4, P=0.003). Patients in the CIN group
      showed a significant rise of Scr level 24, 48, and 72 hours after angiography.
      However, the urine volume had no change before and after angiography. Renal
      function was improved in 12 of 23 patients (52.2%), and deteriorated in 11
      patients (47.8%). Four patients (17.4%) received dialysis. Compared with the non
      reavery group, Scr levels [(194.5 +/- 70.7) micromol/L, (443.8 +/- 282.9)
      micromol/L, respectively] of pre-angiography in renal function recovery group and
      the patients whose dosage was over maximum threshold of contrast-medium (2/12,
      8/11) had significant difference (P < 0.05). CONCLUSIONS: Higher volume of
      contrast-medium is a risk factor of CIN in patients with renal dysfunction. Pre
      angiography Scr level and the contrast-medium volume are correlated with the
      prognosis of CIN in such patients.

PMID- 15960273
TI  - [Clinical analysis of proteinuria and glomerular lesions in Henoch-Schonlein
      purpura nephritis of adults].
AB  - OBJECTIVE: To analyze the characteristics of proteinuria and glomerular lesions
      in Henoch-Schonlein purpura nephritis (HSPN) of adults. METHODS: The pathologic
      results and clinical data of 103 HSPN patients were analyzed. RESULTS: Patients
      with mild or moderate proteinuria accounted for 40.8% and 37.9%, respectively.
      Patients with nephropathic proteinuria accounted for about 21.4%. Severer
      proteinuria resulted in higher blood pressure and increased cholesterol, and
      albumin decreased gradually (P < 0.01); meanwhile, total glomerular lesion,
      tubulointerstitial lesion, and vascular lesion also became severer (P < 0.01).
      CONCLUSION: Proteinuria may indirectly reflect the severity of glomerular lesions
      in HSPN of adults.

PMID- 15960274
TI  - [Bcl-2/Bax gene expression in different types of carotid plaque].
AB  - OBJECTIVE: To investigate Bcl-2/Bax gene expression in different types of carotid
      plaque, and examine the relationship between gene expression and atherosclerotic
      plaque instability and the main cause of brain ischemic events. METHODS: Totally
      42 human carotid plaque specimens obtained during carotid endarterectomy were
      divided into stable group (n=19) and unstable group (n=23) based on
      histopathological studies (HE staining). Eight aortic arteries and their branches
      from hepatic transplantation donors were taken as control group. Bcl-2/Bax was
      detected by immunohistochemistry (IHC) staining (n=42) and in situ hybridization
      (ISH) (n=25, stable 13/unstable 12). RESULTS: Bcl-2 gene expression, which was
      expressed in smooth muscle cells (SMC), endothelial cells (EC), macrophages (MP)
      and foam cells, was detected in 20 and 9 cases in unstable plaque while 11 and 4
      cases in stable plaque by IHC and ISH, respectively (P < 0.05). Bax, which was
      expressed in SMC and MP, was detected in 18 and 11 cases in unstable plaque,
      while 8 and 5 cases in stable plaque by IHC and ISH, respectively (P < 0.05).
      CONCLUSION: The expression rate of Bcl-2/Bax in unstable plaques was higher than
      in stable plaques. Bcl-2 was one of the elements that maintain plaque stability
      whereas Bax was one element that facilitates plaque instability. Therefore, Bcl
      2/Bax expression in different stage of atherosclerosis may be one of the molecule
      regulation mechanisms in carotid atherosclerosis.

PMID- 15960275
TI  - [Clinical pathology, diagnosis, and treatment of mixed growth hormone-and
      prolactin cell adenoma].
AB  - OBJECTIVE: To discuss the clinical pathology and management of mixed growth
      hormone- and prolactin (GH-PRL) cell adenoma. METHOD: Eight patients (4 men and 4
      women, with the mean age of 32.3 year old and duration of symptoms 12 months)
      underwent examination of serum endocrine and magnetic resonance imaging. Clinical
      manifestations included headache, physiognomy of acromegalic patient, large pudgy
      hands and foots, menstrual dysfunction, amenorrhea, galactorrhea, and descending
      vision. Patients underwent transsphenoidal microsurgery of mixed GH-PRL pituitary
      adenoma between 1986 and 2004. RESULTS: The hypersecretion of GH and PRL was
      relieved after operation. Headache was obviously improved in all patients. In 5
      cases the menstrual dysfunction and amenorrhea were recovered. In 4 cases the
      galactorrhea and descending vision disappeared. CONCLUSIONS: The diagnosis of
      mixed GH-PRL pituitary adenoma can be made according to the results examination
      of serum endocrine, pathology and clinical manifestations. Its endocrine features
      are related to the invasion extent of the adenoma. The transsphenoidal approach
      is the preferred treatment for mixed GH-PRL pituitary adenoma.

PMID- 15960276
TI  - [Adjacent segment disease after spine fusion and instrumentation].
AB  - Spinal instrumentation is a common method for the treatment of spinal disorders,
      but it can lead to the changes of spine biomechanics. Because of the stress
      changes, accelerated degeneration of the adjacent segment may occur as time goes
      by, namely adjacent segment disease. The accelerated degeneration can lead to
      secondary spinal stenosis, articulated joint degeneration, acquired
      spondylolisthesis, and spine instability, and some patients may have to receive
      surgery again. In recent years, the researchers gradually recognized the
      importance of this disease, and began to investigate its pathogenesis and
      management.

PMID- 15960277
TI  - [Progress in electrophysiologic and clinical examination for dorsal spinal cord
      injury].
AB  - Electrophysiologic examination of dorsal spinal cord injury (DSCI) is focused on
      transcranial magnetic stimulation induced motor evoked potentials. It were
      recorded at thenar muscles, exector spinae muscle, intercostals muscle, and
      internal oblique muscles. In complete spinal cord injury, the exector musle motor
      evoked potentials may occur although clinically that muscle shows no recovery.
      The ipsilateral exector and internal oblique muscles may be distributed by non
      cross fibers in cerebrospinal tract. The progress in clinical sensory examination
      includes cutaneous electrical perceptional sensory threshold and quantitative
      sensory test. The former is more sensitive than two-points discrepentive test.
      Quantitative sensory test includes light touch threshold, vibration perceptual
      threshold, thermal threshold, pain, and cutaneous axon flare respone. It has been
      used in DSCI patients above and below the injury level. The thermal threshold
      elevates above the injury level in complete and incomplete DSCI patients.

PMID- 15960278
TI  - [Cardiovascular effects of phytoestrogens].
AB  - Phytoestrogens are bioactive substances existing in natural plants. They have
      similar molecular structure to those of estrogens. In this article we introduced
      their classification and sources, and elucidated their effects on heart from
      aspects involving cardiac function and myocardial electrophysiology. By
      regulating serum lipid metabolism, arterial vessels, cytokine levels, and
      coagulation/fibrinolysis system, phytoestrogens possess the effects of anti
      atherosclerosis and may be used to prevent and treat cardiovascular diseases.

PMID- 15960279
TI  - The changing shape of a medical college.

PMID- 15960281
TI  - Frequency of isolation of shigella serogroups/serotypes and their antimicrobial
      susceptibility pattern in children from slum areas in Karachi.
AB  - OBJECTIVES: To assess the frequency of serogroups and serotypes, as well as the
      antimicrobial susceptibility pattern of Shigella species isolated from known
      cases of diarrhoea and dysentery from Karachi, Pakistan. METHODS: A cross
      sectional study was conducted between January 2002 and March 2003 at Aga Khan
      University on stool samples received from children with diarrhoea and dysentery
      from four low socio-economic areas (Sultanabad, Rehri Goth, Hijrat and Sherpao
      colony) of Karachi. Stool samples yielding growth of Shigella species, were
      further identified for serotypes by slide agglutination. Antibiotics
      susceptibility was performed by Kirby Bauer disk diffusion method. RESULTS: Out
      of 4688 stool samples received, 193 (4.1%) were positive for Shigella species.
      Shigella flexneri was the predominant serogroup (58%) followed by Shigella sonnei
      (16%), Shigella boydii (15%) and Shigella dysentriae being the least common
      (11%). A number of serotypes were isolated in each serogroup, 8 serotypes in S.
      flexneri, 8 serotypes in S. dysenteriae, 9 serotypes in S. boydii, and Phase 1 &
      2 were found in S. sonnei. 17% isolates remained non-serotypeable. All isolates
      were susceptible to Ofloxacin and Ceftriaxone, high rate of resistance was
      observed in Cotrimoxazole (87.75%) and Ampicillin (55.5%). Emerging resistance
      against Nalidixic acid (39%) was observed. CONCLUSION: Shigella still accounts
      for a significant proportion of bacillary dysentery in many tropical and
      subtropical countries. Serotype identification can help in devising strategies
      such as development of effective vaccine for controlling this problem. Increasing
      antibiotic resistance against commonly prescribed drugs signify that treatment
      options have become difficult in cases of severe dysentery.

PMID- 15960280
TI  - Induction of labour with oral misoprostol for prelabour rupture of membranes at
      term.
AB  - OBJECTIVE: To study the efficacy, safety and maternal satisfaction of oral
      misoprostol for induction of labour in patients with prelabour rupture of
      membrane at term (PROM). METHODS: Pregnant women with singleton pregnancy at term
      with cephalic presentation with prelabour rupture of membranes having no other
      obstetric and maternal contraindications for induction of labour, were included
      in the study. Patients were given 50ugm of oral misoprostol at six hourly
      intervals for a total of three doses or until labour was established. RESULTS: Of
      the 104 patients included in the study, 28 (26.9%) were primigraivda and 72.1%
      were multigravida. Induction delivery internal was shorter in multigravida and
      longer in primigraivda. Patients with Bishop score of less than 5 had a longer
      induction delivery interval as compared to patients with Bishop score more than
      5. Significant side effects included nausea and vomiting in 68 patients (65.3%).
      Vaginal delivery was achieved in 80.7% with Cesarean section in 19.2% of
      patients. Neonatal outcome was good with no stillbirths and only two neonatal
      deaths. A large number, 98 (94.2%) of women were satisfied with induction of
      labour with oral misoprostol in PROM. CONCLUSION: Active management with oral
      misoprostol resulted in more women going into labour and delivering within 24
      hours of PROM with no significant maternal and neonatal complications.

PMID- 15960282
TI  - Bilirubin pigments in the first meconium of newborn infants.
AB  - OBJECTIVE: To determine the pattern of excretion of total bilirubin IXa and IXb
      in the first meconium of newborn infants. METHODS: First two newborns of varying
      gestational age were selected every week through random sampling from the
      neonatal unit. Of the 41 newborn infants selected 8 expired before meconium
      passage, hence the results are from 33 newborns. Meconium was collected and
      stored at -20 degrees C, protected by aluminium foil. Samples were defrosted,
      vortex mixed with equal amount of dimethyl-sulfoxide, centrifuged, and analyzed
      by HPLC. RESULTS: Unconjugated Bilirubin-IXalpha and -IXbeta were identified and
      quantitative estimation of Bilirubin-IXa done. Bilirubin-IXb was greater than 50%
      of the total, in the first meconium of the newborn. Amount of bilirubin excreted
      in meconium was 29.2 - 90.8 mg [0.051 - 0.155 mmol] per sample of meconium
      passed. Amount was 9.7 mg/ Kg of body weight in term newborn and 12 mg/kg in
      preterm. CONCLUSION: The amount of bilirubin -IXb decreases and bilirubin-IXa
      increases with increasing gestational age. Newborns with birth asphyxia (BA) had
      significantly greater quantity of bilirubin in meconium, compared to infants
      without BA.

PMID- 15960283
TI  - Hospital waste management in the teaching hospitals of Karachi.
AB  - OBJECTIVE: To evaluate the current practices of segregation approaches, storage
      arrangements, collection and disposal systems in the teaching hospitals of
      Karachi. METHODS: A cross-sectional survey was conducted in eight teaching
      hospitals of Karachi, using convenient sampling technique. The instrument of
      research was a self administered questionnaire, with four sections, relating to
      the general information of the institution, administrative information,
      information regarding Health Waste Management personnel and a check-list of
      Hospital Waste Management activities. RESULTS: Out of eight hospitals visited 2
      (25%) were segregating sharps, pathological waste, chemical, infectious,
      pharmaceutical and pressurized containers at source. For handling potentially
      dangerous waste, two (25%) hospitals provided essential protective gears to its
      waste handlers. Only one (12.5%) hospital arranged training sessions for its
      waste handling staff regularly. Five (62.5%) hospitals had storage areas but
      mostly it was not protected from access of scavengers. Five (62.5%) hospitals
      disposed off their hazardous waste by burning in incinerators, two (25%) disposed
      off by municipal landfills and one (12.5%) was burning waste in open air without
      any specific treatment. No record of waste was generally maintained. Only two
      (25%) hospitals had well documented guidelines for waste management and a proper
      waste management team. CONCLUSION: There should be proper training and management
      regarding awareness and practices of waste disposal. Research must be undertaken
      to seal existing gaps in the knowledge about hospital waste management. The
      hospital waste management guidelines enacted on 7th June 2004 should be followed
      and regulated by law enforcement agencies rigorously.

PMID- 15960284
TI  - Awareness about common diseases in selected female college students of Karachi.
AB  - OBJECTIVE: To determine the level of awareness about five common diseases,
      namely: Tuberculosis (TB), Typhoid, Hepatitis B, Hepatitis C and HIV/AIDS among
      college female students of Karachi. METHODS: A cross-sectional survey of female
      students aged 16-21 years from three colleges selected by convenient sampling
      method was conducted from January to May 2004. Data was collected through a self
      administered questionnaire. RESULTS: A large number of students (71%) knew that
      typhoid spreads by eating contaminated food and drinking infected water. Majority
      (84%) knew about cough as a mode of spread for TB whereas 69% thought that TB
      could spread through sneeze of a TB patient. Regarding AIDS, 90% knew that it is
      sexually transmitted. Majority (87%) knew about the association of hepatitis B
      and contaminated needles; 64% were aware of hepatitis C and abuse of contaminated
      needles; 88% knew about the spread of HIV by the use of contaminated needles. A
      large number (92%) mentioned television as their main source of information.
      CONCLUSION: The general level of awareness regarding HIV/AIDS transmission was
      satisfactory among college girls in this study. The level of awareness of the
      young educated females about the modes of spread of typhoid, TB, hepatitis B and
      C is low. This study emphasizes the effectiveness of health education campaign
      regarding common infectious diseases, especially in young girls.

PMID- 15960285
TI  - Ductal carcinoma in situ (DCIS) in Karachi.
AB  - OBJECTIVE: To study the frequency of ductal carcinoma in situ (DCIS) in a large
      pathology series. DCIS is a proliferation of non-invasive, malignant epithelial
      cells within the ductolobular system of the breast. It is a heterogeneous entity
      with several morphologic variants that differ in gross appearance, growth
      pattern, cytologic features, mammography, and malignant potential. METHODS: The
      data of The Aga Khan University' Pathology Department, diagnosed on the basis of
      histopathology, during a 6-year period (1st January 1998 to 31st December 2003)
      was reviewed, all cases of DCIS studied, and data was analyzed with the help of
      analytical software SPSS. RESULTS: Thirty-eight cases of DCIS were reported to
      the Aga Khan University Pathology Department, during a 6-year period (1998 to
      2003), comprising approximately 1% of all breast cancers reported to the unit in
      the same period. The mean age of the patients at diagnosis was 48.95 years (CI
      95% 44.6; 53.3). Approximately half the cases occurred in the 45-54 year age
      group (figure 1). Two cases (5.3%) were recurrences with previous lumpectomy
      scars. Comedo necrosis was observed in five (13.2%) cases, whereas 33 (86.8%)
      cases were non-comedo type. The clinical presentation was a palpable mass
      (92.1%), nipple discharge (5.3%) or clinically occult lesions diagnosed on
      mammography (2.6%). Approximately half the patients presented with a grade 2
      disease. Atypical ductal hyperplasia was observed in a third of the cases,
      predominantly associated with a grade 1 and 2 disease. The estrogen and,
      progesterone receptor status was studied in 12 (31.6%) cases. Estrogen positivity
      was observed in 11 (91.7%) cases and progesterone positivity in 7 (58.3%) cases.
      Microcalcification was observed in four (10.6%) cases. CONCLUSION: The cases
      reported in this study are the indolent grade 1 or 2 cases with a non-comedo
      pattern, and a positive estrogen and progesterone receptor status. If untreated,
      only 40% of these innocuous forms of DCIS become invasive over a time span of
      approximately 25-30 years. In Pakistan we are missing the more aggressive forms
      of DCIS which have a shorter transition to invasive carcinoma.

PMID- 15960286
TI  - Eperisone compared to physiotherapy on muscular tone of stroke patients: a
      prospective randomized open study.
AB  - OBJECTIVES: To compare the effects of Eperisone, a muscle relaxant and
      physiotherapy on the muscular tone after stroke. METHODS: Twenty six (26)
      patients were included from age 15 to 75 years in an open prospective randomized
      study of three weeks duration and were treated with either Eperisone (n=13) or
      were advised to undergo formal physiotherapy (n=13) at the department of
      physiotherapy PIMS. The end point was observed in the form of change in the grade
      of tone. Safety and tolerability was assessed on the basis of adverse events.
      RESULTS: Eperisone was found to be comparable to physiotherapy in reducing the
      spasticity in patients after stroke and improved the grade of tone from 3-2
      (n=2), 4-3 (n=2), 2-1 (n=2). The safety analysis showed persistent vomiting
      (n=1), fatigue (n=1), headache and dry mouth (n=2), epigastric pain (n=1) and
      slight changes in blood pressure under Eperisone which was generally well
      tolerated by the patients. CONCLUSION: Eperisone was found to be comparable to
      physiotherapy in its effects to improve spasticity in patients after stroke
      (p>0.05).

PMID- 15960287
TI  - Expression of mesothelial markers in malignant mesotheliomas: an
      immunohistochemical evaluation of 173 cases.
AB  - OBJECTIVE: To see the distribution of Calretinin, thrombomodulin, CK5/6 and HBME
      1 markers in various subtypes of mesotheliomas and extend the published data on
      this topic. The positivity of adenocarcinoma specific markers (CEA and BerEP4) in
      malignant mesotheliomas have also been evaluated. METHODS: Various markers in 173
      cases of malignant mesotheliomas received over a period of 8 years were evaluated
      by immunohistochemistry. RESULTS: In majority of malignant mesotheliomas i.e.,
      epithelioid and biphasic types, the positive staining patterns complement the
      gold standard histologic diagnosis. However, in a small minority mainly
      sarcomatoid variant, heavy reliance cannot be placed on these markers. CEA and
      BerEP4 are useful negative markers of mesotheliomas, although occasionally these
      are positive in clear cut mesotheliomas. CONCLUSIONS: Specificity of various
      markers in malignant mesotheliomas should be assessed according to histologic
      subtypes. The existing generation of markers is not reliable in diagnosis of
      sarcomatoid mesotheliomas. Fortunately this forms only a small group of
      mesothelial malignancy. In common epithelioid and biphasic variants calretinin,
      thrombomodulin, CK5/6, HBME-1 are sensitive positive markers whereas CEA and
      BerEP4 are negative markers of malignant mesotheliomas.

PMID- 15960288
TI  - Outcome of patient referral made by the lady health workers in Karachi, Pakistan.
AB  - The outcome and consequences of referral made by the Lady Health Workers (LHWs)
      are largely unknown. This cross sectional study was conducted as part of a larger
      study and aims to assess outcome of patients' referrals made by the LHWs in
      Karachi, Pakistan. Only 4% of patients referred visited government facilities,
      the rest having visited private physicians and in-formal practitioners. The
      median cost of the treatment was 200 Pakistani Rupees (PKR) and 1230 PKR as out 
      patient and in-patient respectively with almost half the patients (41.3%)
      borrowed money to finance their treatment. Seventy-eight (31.6%) patients were
      not satisfied with the management they received from the referral health
      facilities. Major reasons cited were non-improvement in their condition,
      expensive, long waiting time and rudeness of the health facility staff. Factors
      identified in this study should be taken into account to ensure continuity and
      quality of care and to provide efficient, effective and equitable health services
      to all.

PMID- 15960289
TI  - Hairy cell leukemia: clinical presentation and long term follow up after
      treatment with 2-chlorodeoxyadenosine (2-CdA).
AB  - The aim of the study was to the clinical features and long term follow up after
      treatment with Cladarbine in a tertiary care hospital. Seven patients with hairy
      cell leukemia were diagnosed between January 1990 till December 2003. Diagnosis
      in all the patients was established by bone marrow aspirates and trephine biopsy
      along with TRAP. In two patients the diagnosis was supplemented by flowcytometry
      and in another two patients by splenectomy. Six patients were male while one was
      female. Mean age was 47.7 years (range 36-64). Most common presenting features
      were pallor and weakness (n=5). All patients had splenomegaly. Blood count at
      presentation revealed that one patient had bicytopenia, two had isolated
      thrombocytopenia, and three had pancytopenia. Treatment responses were evaluable
      in seven patients. Complete response was seen in six patients (85.7%). One
      patient died after two months due to sepsis while 3 (50%) patients relapsed.
      Those who relapsed received another course of CDA and have maintained remission
      with a median duration of response of 48 months (20-48). From this small series
      we can conclude that CDA is an effective treatment for HCL and even it works very
      well in relapsed cases.

PMID- 15960290
TI  - High failure rate in postgraduate medical examinations--sign of a widespread
      disease?

PMID- 15960291
TI  - Anaphylactic reaction after intramuscular injection of cyanocobalamin (vitamin
      B12): a case report.
AB  - We report a case of anaphylactic reaction to intramuscular injection of
      cyanocobalamin. This 52-year-old lady was diagnosed as a case of megaloblastic
      anemia secondary to dietary vitamin B12 deficiency. She had severe anaphylactic
      reaction after the parenteral administration of cyanocobalamine. Later she
      received oral vitamin B12 with no adverse effects. The purpose of this case
      report is to draw attention to the hypersensitive reaction to injectable vitamin
      B12, which is rarely seen. This could be due to sensitization to the vitamin B12
      molecule itself or an IgE mediated reaction. We concluded that anaphylactic
      reaction to vitamin B12 is a rare but serious side effect and it should be kept
      in mind while the drug is being administered to the patient, especially via the
      parenteral route.

PMID- 15960292
TI  - Primary splenic hydatid cyst: a case report with characteristic imaging
      appearance.
AB  - A middle-aged lady presented with pain, tenderness and swelling in the left
      hypochondrium since one month. She had a history of contact with dogs and grazing
      animals. Sonography and computed tomography showed the pathognomonic signs of
      hydatid disease. The patient refused surgical treatment. She was discharged on
      Albendazole therapy and did not return for a follow up.

PMID- 15960293
TI  - Knowledge of type 2 diabetic patients about their illness: pilot project.
AB  - OBJECTIVE: To evaluate the baseline level of knowledge and awareness of diabetic
      patients about their disease and it's complications. METHODS: It was a Cross
      Sectional Survey conducted at Foundation Clinic, Shifa College of Medicine,
      Islamabad, in April 2004. A structured questionnaire was used. Forty diabetic
      patients were interviewed to know their knowledge attitude and practices about
      diabetes. All data was entered into SPSS version 10.0. The data was re-validated
      and analyzed. RESULTS: Mean age of study participants was 45.35 +/- 13.05 years,
      11(27.5%) were male and 29(72.5%) were female. The mean BMI of the study
      participants was 27.06 +/- 6.29 kg/m2. Majority of the patients 27(67.5%) had
      type 2 diabetes. The mean fasting blood sugar was 159 +/- 73.89 mg/dl and random
      blood sugar was 200 +/- 91.2 mg/dl, 50% of the patients were using antidiabetic
      drugs regularly and only 15% of the patients were regularly monitoring their
      blood glucose at home using a glucometer. Awareness level of the study
      participants was low. CONCLUSION: The awareness about the disease in majority of
      diabetic patients was not adequate in this study. Routine individual teaching and
      counseling represents an effective educational model.

PMID- 15960294
TI  - Neuropsychiatric care in epilepsy surgery.

PMID- 15960295
TI  - Plasma levels of alpha beta peptides are altered in amnestic mild cognitive
      impairment but not in sporadic Alzheimer's disease.
AB  - Plasma alpha beta levels have been examined in sporadic Alzheimer's disease
      yielding conflicting results; both no difference and an increase in plasma
      concentrations of alpha beta42 and alpha beta40 in sporadic cases of AD as
      compared to controls have been reported. Elevated plasma alpha beta42 levels may
      be detected several years before the onset of symptoms (in mild cognitive
      impairment stadium). Levels of alpha beta40 and alpha beta42 were measured in
      plasma from 54 patients with AD, 39 subjects with MCI and 35 controls using a
      commercially available ELISA. Mean plasma alpha beta42 levels were significantly
      higher in MCI as compared to both AD (P < 0.001) and control subjects (P <
      0.001), while alpha beta40 did not differ between the groups. No correlations
      were observed between alpha beta levels and age, MMSE scores or gender. According
      to ROC curve analysis the maximum accuracy in discriminating MCI versus both
      controls and AD subjects has been achieved using a cut-off value of 3.8.

PMID- 15960296
TI  - Limits of learning enhancements with nicotine in old male rats.
AB  - Findings with young adult humans and animal models suggest that nicotine may
      serve both neuroprotective and cognition enhancing roles in old animals. A pair
      of experiments was conducted to examine drug-induced modification of the
      cholinergic nicotinic receptor subtype on rates of learning by young and aged
      rats. In experiment I males (4-7 months or 20-25 months old) were administered
      nicotine (0.0, 0.3 or 0.7 mg/kg injected s.c. daily) and tested in both a T-maze
      non-spatial discrimination paradigm and a hole board spatial task. Nicotine
      failed to improve acquisition by young animals on either task. Nicotine also
      failed to improve non-spatial learning by old animals. However, both dosages of
      nicotine improved performance by the old males in the spatial paradigm. In
      experiment II, a 5-choice serial discrimination paradigm designed to better
      evaluate visual attention and spatial working memory in aging was used. Groups of
      old male rats were administered nicotine or mecamylamine (2 or 8 mg/kg), an
      antagonist of the nicotinic cholinergic receptor. Results were that the 0.3 mg
      nicotine group learned the task fastest and achieved the highest learning
      asymptote. Both learning rates and final levels of performance were worst in the
      8 mg mecamylamine group. However, the 2 mg mecamylamine rats were the equals of
      the control group and both reached a higher asymptote than the 0.7 mg nicotine
      group. These data suggest that healthy old animals can accrue benefits from
      nicotinic activation but that the benefits are complex, being limited to certain
      dosages and to specific cognitive skills.

PMID- 15960297
TI  - Effect of carvedilol on neuronal survival and poly(ADP-ribose) polymerase
      activity in hippocampus after transient forebrain ischemia.
AB  - Carvedilol a beta-adrenoreceptor antagonist with potent antioxidant properties
      raises high expectations in therapy of ischemia. In this study the effect of
      carvedilol on neuronal survival after transient forebrain ischemia in gerbils was
      investigated. The role of poly(ADP-ribose) polymerase (PARP-1) in this process
      was evaluated. Our data indicated that carvedilol administered subcutaneously in
      a dose of 7 or 70 mg/kg b.w. directly after 5 min of transient forebrain ischemia
      protects significant population of neurons in hippocampal area CA1, but has no
      effect after induction of prolonged 10 min ischemia. Carvedilol significantly
      decreased PARP activity in hippocampus that was markedly increased after both 15
      min and 4 days of reperfusion following 5 min of ischemia. Moreover, carvedilol
      prevented NAD+ depletion after ischemic-reperfusion insult. These results
      indicated that carvedilol protects neurons against death and suggested that
      suppression of PARP activity during reperfusion could be involved in this
      process.

PMID- 15960298
TI  - Enhanced pressor response to centrally administered vasopressin in WKY rats on
      high sodium diet.
AB  - Four week old Wistar-Kyoto (WKY) rats were divided into two groups. The
      experimental group (n = 7) was receiving a high sodium diet (3.28% Na) and the
      control group (n = 7) a normal sodium diet (0.22% Na). After 8 weeks, subjects
      were chronically implanted with the lateral cerebral ventricle (LCV) cannulas and
      with the femoral artery catheters. Three series of experiments were carried out
      on the experimental and control groups. In each series mean arterial pressure
      (MAP) and heart rate (HR) were recorded for 10 min before and 30 min after the
      LCV infusion. In series 1 artificial cerebrospinal fluid (aCSF) was administered
      (2 microl/15 s). In series 2 AVP was infused (20 ng/2 microl aCSF/15 s). In
      series 3 V1a receptor antagonist (V1 ANT), d(CH2)5[Tyr(Me)2,Ala-NH29]AVP, was
      applied (80 ng/microl aCSF/15 s). There was no difference in baseline MAP and HR
      between the experimental and control groups. LCV infusion of aCSF had no effect
      on MAP and HR. LCV infusion of AVP produced a significant increase of MAP, which
      was greater in the group on the high sodium diet than in the group on normal
      sodium diet. The experimental group showed a longer hypertensive effect of
      centrally applied AVP in comparison to the control. LCV administration of V1 ANT
      did not exert a significant effect on circulatory parameters. These results
      suggest that the prolonged high sodium diet does not induce hypertension in WKY
      rats, but it enhances the pressor function of the central vasopressinergic
      system.

PMID- 15960299
TI  - Effects of acute hypergravity exposure and parity on maternal behavior in CD-1
      mice.
AB  - We assessed the behavioral response to acute hypergravity exposure in lactating
      mother mice, Mus musculus of the outbred CD-1 strain. Primiparous or terziparous
      dams were exposed with their litters to a centrifugal force equivalent to 2G
      hypergravity for 1 h daily from postnatal day 2 (P2) to P9. We made detailed
      behavioral observations before, during and after the rotation on selected days to
      identify elements of the maternal behavioral repertoire vulnerable to 2G
      challenge. Licking and nest building were reduced during rotation while mothers
      sniffed and snouted their pups more. Nursing and total time in physical contact
      with pups were relatively stable. The effects of rotation were most pronounced on
      P2, dams appearing to habituate to the treatment with repeated exposure. Dam
      parity had a limited effect on the behavioral response to rotation, primiparous
      mothers tending to spend longer nursing their pups during the rotation and
      showing a greater tendency to lick and nest-build in post-rotation. Differences
      between parity groups diminished over days. Body weight was decreased in rotated
      primiparous dams and their pups gained less weight than stationary controls.
      Ultrasonic vocalization (USV) rates recorded on P2, P5 and P9 seemed to indicate
      delayed behavioral development in rotated pups.

PMID- 15960300
TI  - The expression and function of Sgt1 protein in eukaryotic cells.
AB  - The Sgt1 protein was discovered in yeast but later it was found in other
      eucaryotic organisms, including plants and mammals. It was suggested that the
      Sgt1 protein plays a role in the CBF3 kinetochore and the SCF ubiquitin ligase
      complexes. Since the distribution, properties and functions of the mammalian Sgt1
      have not been extensively studied, we examined the expression of Sgt1 protein in
      the rat tissues and here we report the preliminary results. Using northern and
      western blots we found that the Sgt1 protein is expressed in various tissues and
      that brain, skeletal muscles and spleen contain high levels of this protein and
      its mRNA. Then, by western blot, we checked the localization of Sgt1 in some
      areas of the rat brain such as cortex, cerebellum and hippocampus and we found
      that cerebellum and cortex contain highest amounts of this protein. Using
      immunohistochemistry we found that the Sgt1 protein is present in both neurons
      and glial cells.

PMID- 15960301
TI  - D1 dopamine receptors distribution following photothrombotic stroke in rat
      cerebral cortex.
AB  - The effect of focal photothrombotic stroke on the distribution of D1 dopamine
      receptor (D1R) sites was examined in different cortical areas of rat brain with
      quantitative receptor autoradiography using [3H]SCH23390 as a ligand. Unilateral
      cortical stroke was located in the primary somatosensory cortex. After different
      survival times (1, 7 and 28 days) D1R binding levels were determined in the
      lesion core, penumbra, frontoparietal motor (FrPaM) and somatosensory (FrPaSS)
      areas as well as in homotopic regions in the contralateral hemisphere. One day
      after stroke, D1R density decreased by 36% (P < 0.01) in the lesion core relative
      to sham-operated controls. At 7th day binding density was further reduced by 56%
      (P < 0.002). Twenty-eight days after infarction, D1R binding returned to control
      level. No alterations in D1R binding levels were found in penumbra and other
      investigated regions. We suggest that the return of D1R binding to control level
      in the area initially corresponding to the infarct results from the shrinkage of
      the lesion volume.

PMID- 15960302
TI  - NG2 expressing cells in hippocampal cultures survive neurotoxic insult and retain
      the ability to divide.
AB  - It has been recently proposed that NG2 proteoglycan expressing cells may stand
      for a unique class of glia in adult CNS referred to as oligodendrocyte progenitor
      cells (OPCs). These NG2 positive cells can give rise to mature oligodendrocytes,
      however a large number of them persists in immature stage throughout a lifetime
      and responds to various types of injury. In order to investigate OPCs reactivity
      in vitro, a model of trimethyltin evoked neurodegeneration was used. The results
      demonstrate that NG2 expressing cells survive treatment with the neurotoxin in a
      concentration that injures most of neurons in the culture. Moreover, progenitors
      change their morphology when treated with trimethyltin, upregulate the NG2
      proteoglycan expression and retain the ability to divide.

PMID- 15960303
TI  - Confocal visualization of the effect of short-term locomotor exercise on BDNF and
      TrkB distribution in the lumbar spinal cord of the rat: the enhancement of BDNF
      in dendrites?
AB  - Locomotor exercise increases neurotrophin BDNF and its receptor TrkBFL expression
      in the lumbar spinal cord. Involvement of BDNF/TrkBFL in synaptic transmission
      raises the questions which intracellular compartments are involved in this
      upregulation and whether exercise leads to redistribution of these proteins
      related to the duration of exercise. We have investigated the influence of short
      term (7 days) locomotor exercise (ST) on intracellular distribution of BDNF and
      TrkBFL in the rat lumbar spinal cord comparing it with the effects of long-term
      (28 days) exercise (LT) described earlier. Immunofluorescence (IF) of proteins
      was analyzed with confocal microscopy. ST exercise caused a redistribution of
      perikaryonal BDNF IF toward periphery resulting in an increase of dendritic
      signal. In contrast to an enhancement of perikaryonal BDNF staining following LT,
      no increase of BDNF IF in cell bodies was observed after ST. An increase of
      TrkBFL IF in oligodendrocytes was consistent with that caused by LT. The fibers
      of TrkBFL IF oligodendrocytes surrounding the largest neurons were in close
      apposition to neuronal membrane. We propose that ST exercise causes (1) BDNF
      translocation to dendrites and/or local dendritic synthesis to serve increased
      synaptic activity (2) sensitization of oligodendroglia to BDNF mediated
      responses.

PMID- 15960304
TI  - A single compartment neuron model with activity-dependent conductances during
      NMDA induced activity.
AB  - In most neuron models the values of maximal conductances of membrane ionic
      currents are fixed. In our paper we investigate spiking activity of the neuron
      model activated tonically by NMDA synapse, when the membrane ionic currents are
      dynamically dependent on calcium concentration, as in a model by Abbott and
      coauthors (1993). A spiking neuron model (in Matlab/Simulink environment) is
      based on the properties of lamprey spinal neurons. The basic neuron is a one
      compartment model with voltage-gated Na+, K, Ca2+, KCa+ channels. The Na+ and K+
      currents are described with the dynamic equations of Hodgkin-Huxley model
      (Hodgkin and Huxley 1952). The Ca2+ and KCa+ channels are modeled using
      description of calcium dynamic introduced by Ekeberg and coauthors (1991). The
      model was tonically activated by NMDA synapse described by a kinetic model of
      synaptic transmission. We analyzed the activity of this model and showed that
      when only one of conductances is calcium-dependent, the cell is not able to react
      to and recover from external perturbations.

PMID- 15960305
TI  - Expression of c-Fos in response to stressogenic stimuli in the amygdala of old
      vs. young rats--a preliminary study.
AB  - During aging many of the brain functions became deteriorated or altered. One of
      the most important age related changes is an increase of anxiety level, reported
      both in humans and in animals. Our study was intended to compare c-fos gene
      expression in amygdala, the key structure in anxiety/fear regulation, in old (24
      months) and young (4 months) rats exposed to various behavioral stimulations.
      There were no differences between age groups in basal c-Fos expression. After
      social encounter c-Fos expression level in amygdala increased significantly, but
      still remained independent on age. Significant differences between both groups
      appeared after open field test and immobilization test. Contrary to the findings
      on young adults indicating the correlation between increased anxiety level and
      higher c-Fos expression, old rats showed increased anxiety together with
      significantly lower c-Fos expression.

PMID- 15960306
TI  - Effects of sensory learning on intracortical synaptic transmission in the barrel
      cortex of mice.
AB  - Pairing tactile stimulation of a row of whiskers with a tail shock results in an
      expansion of the functional representation of the stimulated whiskers within the
      primary somatosensory cortex of mice. Using the same paradigm, the present study
      examined field potentials evoked in ex vivo slices of the barrel cortex. The
      amplitude of responses, evoked by single and repetitive stimuli in layer IV-layer
      II/III pathway contained within the barrel column corresponding to the whisker
      stimulated during training, was unchanged. In contrast, in a transcolumnar
      pathway from the "trained" barrel to layer II/III of the neighboring, "untrained"
      column, the amplitude of responses was reduced and responses to trains of stimuli
      applied at 40 Hz, but not at lower frequencies, depressed faster. These data are
      suggestive of a selective weakening of excitatory transmission and/or enhancement
      of inhibitory transmission in transcolumnar pathways, which accompany associative
      learning-induced cortical plasticity.

PMID- 15960307
TI  - Acoustic startle response in the opossum Monodelphis domestica in comparison with
      the Wistar albino rat.
AB  - The acoustic startle response (ASR) was studied in 20 gray short-tailed opossums
      (Monodelphis domestica) and its characteristics were compared with those obtained
      from responses of 20 Wistar albino rats. The animals were exposed to 10 ms, 110
      dB white noise acoustic pulses in the Coulbourn apparatus. Amplitude of ASR was
      normalized to the weight of animals and then analyzed. The results show that
      probability of a freezing response is much higher in the opossums that generally
      respond with lower startle amplitudes in comparison to rats. These differences
      may reflect different emotional characteristics of the two species, different
      reactions to fear in opossum and/or different ecological specializations of the
      two species.

PMID- 15960308
TI  - One-trial visual recognition in cats.
AB  - The ability of normal cats to perform delayed matching- and nonmatching-to-sample
      with trial-unique stimuli was investigated both in a modified Wisconsin General
      Testing Apparatus requiring manipulatory responses and in a Nencki-type testing
      room requiring locomotor responses. Cats trained in the WGTA learned the two
      tasks at about the same rate, on average, as that reported for monkeys. However,
      unlike monkeys, whose strong preference for novelty facilitates their learning of
      the nonmatching rule and retards their learning of the matching rule, the cats
      learned the two different rules at about the same rate, suggesting that cats do
      not share the monkey's strong preference for novelty. In contrast to their
      relatively rapid learning of the manipulatory versions of the two tasks, cats
      learned the locomotor versions only slowly or even failed to learn. Experimental
      analysis indicated that a major source of the cats' difficulty on these locomotor
      versions was interference from a strong tendency in the large testing room to use
      visuospatial strategies. Nevertheless, once the matching or nonmatching rule was
      learned at short delays, whether in the WGTA or the testing room, the cats
      performed at criterion levels without further training even at delays of 10
      minutes, indicating that this species, like monkeys, has a highly developed long
      term recognition memory ability.

PMID- 15960309
TI  - Brain preconditioning and obstructive sleep apnea syndrome.
AB  - Intermittent hypoxia stimulates the development of adaptive responses, called
      preconditioning. This process is partially mediated by genetic remodeling, via
      hypoxia inducible factor (HIF), which induces long-term adaptation processes and
      is responsible for the increase of levels of vascular endothelial growth factor
      (VEGF), erythropoietin (Epo), atrial natriuretic peptide (ANP), and nitric oxide
      (NO). The synthesis of brain-derived neurotrophic factor (BDNF) participates in
      the control of neural plasticity after hypoxia. The mechanisms of neuroprotection
      against hypoxia may be related to vascular adjustments and to central neurogenic
      neuroprotection. Some of the factors known to be involved in the development of
      the mechanism of neuroprotection are also present in the responses to repetitive
      apneas that occur during sleep in patients with obstructive sleep apnea (OSA)
      syndrome, who are frequently exposed to severe sleep hypoxemia. It appears that
      OSA syndrome represents a clinical example of preconditioning and the development
      of adaptive responses to intermittent hypoxia.

PMID- 15960310
TI  - Rabbit paralytic tremor phenotype--a plp1 gene mutation as a model of human
      Pelizaeus-Merzbacher disease.
AB  - The paralytic tremor (pt) disease in rabbits results from a point mutation in a
      plp gene and manifests itself by a broad range of neurological signs. Biochemical
      studies have shown that myelinogenesis is retarded and deficient in mutant
      rabbits. Myelin sheaths are usually thin and malformed. The number of
      oligodendrocytes is normal, however their differentiation and maturation is
      prolonged. The effects of the pt mutation were investigated in morphological,
      biochemical and molecular studies, resulting in the well-documented
      characteristics of the disease. The pt phenotype and its detailed characteristics
      make the mutated rabbit a good model of Pelizaeus-Merzbacher disease.

PMID- 15960311
TI  - Topographical significance of membrane skeletal component protein 4.1 B in
      mammalian organs.
AB  - The polarized architecture of epithelial cells is a fundamental determinant of
      cell structures and functions. Both formation and orientation of proper
      epithelial polarity are needed for cell-cell or cell-matrix adhesion, signal
      transduction and cytoskeletal interactions of multimolecular complexes at apical,
      lateral and basal cell membranes. These cell membrane domains are usually
      segregated by some junctional complexes. Recent molecular genetic studies on the
      anchor structure between myelin sheaths and axons have indicated the specific
      molecular organization for polarization of axolemma and the myelin sheaths at
      paranodes, termed 'septate-like junctions'. It was also speculated that other
      mammalian organs may use a similar junctional system. The protein 4.1 B was
      originally found to be localized in paranodes and juxtaparanodes of myelinated
      nerve fibers. Our recent immunohistochemical studies on protein 4.1B have
      indicated its significance for the cell-cell and/or cell-matrix adhesion in
      various rodent organs. The protein 4.1 family of proteins have been supposed to
      possess variable molecular domains relating to cell adhesion, ion balance,
      receptor responses and signal transduction. Therefore, more precise studies on
      the molecular structure and the functional domains of protein 4.1B, as well as on
      its changes under physiological and pathological conditions, may provide a clue
      for organogenesis in various mammalian organs.

PMID- 15960312
TI  - Salivary gland morphogenesis and basement membranes.
AB  - The basement membrane separates the epithelium from the surrounding mesenchyme
      and plays an essential role in the development of various epithelial-mesenchymal
      organs. Among these, the submandibular salivary gland (SMG) has been chosen to
      review the expression patterns and roles of the epithelial basement membrane and
      its components, in particular the laminins, during SMG morphogenesis. At the
      outset, a brief description of SMG development is provided with special reference
      to changes in the epithelial architecture and the epithelial basement membrane.
      The restricted expression patterns of various laminin isoforms in the developing
      SMGs are also summarized. Furthermore, an overview is given of several lines of
      experimental evidence that indicate significant but distinct roles for laminin-1
      and laminin-10, their individual domains and their receptor-mediated signaling in
      SMG morphogenesis.

PMID- 15960313
TI  - synaptic organization of the glomerulus in the main olfactory bulb: compartments
      of the glomerulus and heterogeneity of the periglomerular cells.
AB  - According to the combinatorial receptor and glomerular codes for odors, the fine
      tuning of the output level from each glomerulus is assumed to be important for
      information processing in the olfactory system, which may be regulated by
      numerous elements, such as olfactory nerves (ONs), periglomerular (PG) cells,
      centrifugal nerves and even various interneurons, such as granule cells, making
      synapses outside the glomeruli. Recently, structural and physiological analyses
      at the cellular level started to reveal that the neuronal organization of the
      olfactory bulb may be more complex than previously thought. In the present paper,
      we describe the following six points of the structural organization of the
      glomerulus, revealed by confocal laser scanning microscopy and electron
      microscopy analyses of rats, mice and other mammals: (i) the chemical
      heterogeneity of PG cells; (ii) compartmental organization of the glomerulus,
      with each glomerulus consisting of two compartments, the ON zone and the non-ON
      zone; (iii) the heterogeneity of PG cells in terms of their structural and
      synaptic features, whereby type 1 PG cells send their intraglomerular dendrites
      into both the ON and non-ON zones and type 2 PG cells send their intraglomerular
      dendrites only into the non-ON zone, thus receiving either few synapses from the
      ON terminals, if present, or none at all; (iv) the spatial relationship of
      mitral/tufted cell dendritic processes with ON terminals and PG cell dendrites;
      (v) complex neuronal interactions via chemical synapses and gap junctions in the
      glomerulus; and (vi) comparative aspects of the organization of the main
      olfactory bulb.

PMID- 15960314
TI  - Expression of insulin receptor substrates 1-3, glucose transporters GLUT-1-4,
      signal regulatory protein 1alpha, phosphatidylinositol 3-kinase and protein
      kinase B at the protein level in the human testis.
AB  - Insulin receptor substrates (IRS) mediate the biological actions of insulin,
      growth factors and cytokines. This action is via receptor-mediated tyrosine
      phosphorylation of IRS proteins. The aim of present study was to demonstrate the
      distribution of IRS-1-3, the glucose transporter class I subfamily (GLUT-1-4),
      signal regulatory protein 1alpha (SIRP1alpha), protein kinase B (PKB) and
      phosphatidylinositol kinase (PI3-K) in the human testis to determine whether
      signal transduction mediated by these proteins is active in testicular cells. In
      the present study, the expression of IRS-1-3, GLUT-1-4, SIRP1alpha, P13-K and PKB
      was studied in the human testis at the protein level using immunohistochemistry
      and western blotting. A positive immunoreaction for IRS-1 was found in the human
      testis in peritubular myoid cells and macrophage-like interstitial cells. A
      positive immunoreaction for GLUT-3 was found in the human testis in Sertoli
      cells, peritubular myoid cells, early spermatocytes, macrophage-like interstitial
      cells and cells in the small vessels walls. Western blotting demonstrated IRS-1,
      IRS-2 and GLUT-3 proteins in the human testis. Expression of IRS-3, GLUT-1, GLUT
      2, GLUT-4, SIRP1alpha, P13-K and PKB was not detected in the human testis. The
      results of the present study suggest that proteins like insulin and certain
      cytokines using IRS-1, IRS-2 and GLUT-3 in their signal transduction pathways can
      have effects on different cell types of the testis in humans.

PMID- 15960315
TI  - Structure of the respiratory tract of the red-bellied newt Cynops pyrrhogaster,
      with reference to serotonin-positive neuroepithelial endocrine cells.
AB  - To investigate the distribution of serotonin-positive neuroepithelial endocrine
      (NEE) cells in the respiratory tract of the red-bellied newt Cynops pyrrhogaster,
      serial sections of the respiratory tract were stained using immunohistochemical
      methods for serotonin, a periodic acid-Schiff method and hematoxylin-eosin
      staining. The respiratory tract of the red-bellied newt consisted of a tubular
      laryngotrachea and two pulmonary sacs. Serotonin-positive solitary NEE cells were
      distributed widely throughout the ciliomucous epithelium of the laryngotrachea.
      The innervated clusters of NEE cells, termed neuroepithelial bodies, were rarely
      found in the caudal portion of the laryngotrachea. The density of NEE cells was
      high in the middle portion of the laryngotrachea, particularly in the region
      surrounded by a striated laryngeal sphincter, and the densities were low
      cranially towards the aditus laryngis and caudally in the pulmonary sacs, the
      epithelium of which consisted of both ciliomucous epithelial cells and non
      ciliated respiratory epithelial cells or pneumocytes. The NEE cells were not
      observed in the vicinity of non-ciliated respiratory epithelial cells. The
      morphology and distribution of serotonin-positive NEE cells in the respiratory
      tract of the red-bellied newt were similar to those described in mammals,
      including humans. The close localization of NEE cells with ciliary and mucous
      cells and the distribution of NEE cells in the laryngotrachea suggest that NEE
      cells play important roles in the defense and repair of the ciliomucous
      epithelium, such as increasing mucous secretion, ciliary beat frequency and the
      proliferation of epithelial cells.

PMID- 15960317
TI  - Major anatomical variations of the tracheobronchial tree: bronchoscopic
      observation.
AB  - Fiberoptic and rigid bronchoscopy are widely used diagnostic and therapeutic
      tools in pulmonary medicine. Investigators often neglect the bronchial
      variations; however, bronchial variations may have important implications for
      bronchoscopy, brachytherapy, pulmonary resections and intubations. It is accepted
      that anatomic variations of the airways are due to anomalies in the development
      of the lungs. As a result, lung buds grow to an inappropriate number or arise at
      atypical sites. In the present study, we tried to determine the incidence of
      bronchial variations in our region. We investigated 2550 consecutive reports of
      bronchoscopy retrospectively. Major variations of the tracheobronchial tree were
      found in 2.6% of patients examined by bronchoscopy. The most frequent finding was
      a bifurcate pattern in the right upper lobe (47.7%). The variations were
      localized to the right upper lobe in 71.6% of patients. Male predominance was
      observed in all anatomic variations except one.

PMID- 15960316
TI  - Expression of glial cell line-derived neurotrophic factor (GDNF) and GDNF family
      receptor alpha1 in mouse taste bud cells after denervation.
AB  - Glial cell line-derived neurotrophic' factor (GDNF) has been isolated as a
      neurotrophic factor that affects the survival and maintenance of central and
      peripheral neurons. Using immunocytochemical methods, we examined whether the
      taste bud cells in mouse circumvallate papillae after transection of the
      glossopharyngeal nerves expressed GDNF and its receptor, GDNF family receptor
      alpha1 (GFRalpha1). By 5 and 10 days after denervation, the number of taste buds
      had decreased markedly; however, the remaining taste bud cells still expressed
      GDNF and GFRalpha1. By 14 days after denervation, most of the taste buds had
      disappeared and GDNF- and GFRalpha1-immunoreactive cells were not seen. By 4
      weeks after denervation, numerous TrkB-immunoreactive nerve fibers had invaded
      the papilla and a few taste buds expressing GDNF and GFRalpha1 had regenerated.
      Thus, GDNF- and GFRalpha1-immunoreactive taste bud cells after denervation
      vanished following the disappearance of the taste buds and reappeared at the same
      time as the taste buds reappeared.

PMID- 15960318
TI  - Consideration of the potential courses of the common iliac artery.
AB  - We encountered a rare case of the left common iliac artery in a 92-year-old
      Japanese female cadaver during dissection practice for medical students. The
      artery entered into the small pelvis without branching to the external iliac
      artery. There, it went down slightly medially and then turned laterally and
      passed behind the first sacral nerve. The artery ran anterolaterally further and
      returned to the greater pelvis and became the external iliac artery, which
      continued to the femoral artery as usual. During the course in the small pelvis,
      the artery branched to give rise to each branch of the internal iliac artery. We
      speculate that in the present case, a communication between the median sacral
      artery and the superior gluteal artery, passing behind the first sacral nerve,
      enlarged and compensated the usual common iliac artery.

PMID- 15960320
TI  - WHO bid to reduce maternal mortality.

PMID- 15960319
TI  - Challenges for the future.

PMID- 15960321
TI  - Four months on...life after the Boxing Day tsunami.

PMID- 15960322
TI  - The first birth.

PMID- 15960323
TI  - Midwives and women in partnership.

PMID- 15960324
TI  - Every child matters: change for children.

PMID- 15960325
TI  - Skin-to-skin contact: therapy or treatment?

PMID- 15960326
TI  - Midwifery practice in New Zealand: a student perspective.

PMID- 15960327
TI  - Designing questionnaires for midwifery research.

PMID- 15960328
TI  - Newborn blood spot screening.
AB  - The U.K. Newborn Screening Programme Centre (UKNSPC) launched the first UK-wide
      standards and policies for newborn blood spot screening, together with a national
      pre-screening information leaflet for parents in December 2004. These standards
      are included in a document pack that has been sent recently to all heads of
      midwifery and local screening coordinators. This article describes the standards
      and policies, as well as the supporting guidelines, that are relevant to
      midwifery.

PMID- 15960329
TI  - Pilates and pregnancy.
AB  - Pregnancy is associated with a number of musculoskeletal problems. It is
      important to educate all mothers, as well as those involved in ante- and
      postnatal care with advice on bras and exercises that are safe in pregnancy (in
      particular pelvic floor exercises). There is not much that can be done to alter
      the inevitable physiological and hormonal changes of pregnancy. However, by
      strengthening the core stabilising muscles around the pelvis and spine, and
      improving the breathing pattern, it is hoped that one can optimise the body for
      the challenges it may face. Pilates is based on the principle that a central core
      is developed and then movements are introduced to challenge this core stability.
      This philosophy is clearly applicable in pregnancy--a significant test both
      mentally and physically on the mother's body. By maximising the mother's core
      stability before and during pregnancy, it should be possible to limit any
      potential harm. Returning to exercise soon after the birth is important for the
      mother's physical and mental wellbeing--she looks after her baby's body for nine
      months, who cares for hers?

PMID- 15960330
TI  - Complementary therapies: moving forward.

PMID- 15960331
TI  - New fathers, work and parenthood.

PMID- 15960332
TI  - Amniotomy: to do or not to do?

PMID- 15960333
TI  - Every midwife should have a PRINCE.

PMID- 15960334
TI  - Breastfeeding advice.

PMID- 15960335
TI  - An issue that came to my attention recently regarding child benefit.

PMID- 15960336
TI  - Should midwives be promoting and providing home birth?

PMID- 15960337
TI  - [Trauma registry at the Niguarda Ca' Granda Hospital of Milano: epidemiology and
      quality assessment].
AB  - OBJECTIVE: In a Trauma System, Trauma Registry allows the assessment of
      epidemiology and quality of patient care. MATERIALS AND METHODS: Data about
      trauma patients admitted to Ospedale Niguarda Emergency Department from October
      1, 2002 to June 30, 2003 with ICD9CM code 800-939.9 and 950-959.9 were
      prospectively recorded. Injury severity score (ISS) and revised trauma score
      (RTS) were calculated and probability of survival (Ps) was derived. RESULTS:
      During the study period 1811 trauma patients were admitted, and 271 (14.96%) were
      consistent with triage criteria of severity. Among these, survivors were 220
      (81.18%) and blunt trauma 95.94%. Injuries of the central nervous system with
      (11.76%) or without (50.98%) hemodynamic instability or hemodynamic instability
      alone (31.37%), were the principal causes of death. An ISS greater than 15 was
      observed in 61.25% with an overtriage of 38.75%. Seventy seven patients accepted
      without triage criteria of severity died or were admitted to intensive care unit
      with an undertriage of 5%. Ps among victims was 22.35 +/- 27.19 and possible
      preventable deaths were 6 (11.76%). No frankly preventable death was recorded.
      DISCUSSION: Standard pre-hospital triage criteria are associated with significant
      over and undertriage. Data collection using large population-based data base
      increases epidemiologic value of trauma registry. Analysis of Ps identifies cases
      who need clinical discussion to assess adequacy of treatment. CONCLUSIONS:
      Prospective data collection in a trauma registry may provide all informations
      useful to improve quality of trauma patient care.

PMID- 15960338
TI  - [Definitive breast cancer surgery as an outpatient: rationale and our
      experience].
AB  - INTRODUCTION: The objective of this study was to evaluate the feasibility of
      outpatient breast definitive surgery. CASE AND METHODS: Between January 2001 and
      September 2003 181 definitive breast cancer surgical approaches were performed at
      Surgical Department of Genoa University on 173 patients. Mean age was 60 years
      (28-92). All the patients were discharged the day of surgery or the day after in
      the morning. RESULTS: There were no major complications or deaths. The specific
      complication rate was similar to inpatient setting and there was no readmission.
      The patients' quality of life and satisfaction were satisfactory or good.
      DISCUSSION: In conclusion, holding in due consideration some philosophical and
      technical changes, breast cancer surgery can be safely and comfortably performed
      on an outpatient basis.

PMID- 15960339
TI  - Treatment of complications of hepatic hydatid disease by ERCP: our experience.
AB  - BACKGROUND: The aim of this study was to evaluate the effectiveness of endoscopic
      sphincterotomy and positioning of naso-biliary drain or biliary endoprosthesis
      for preoperative and postoperative complications of hepatic hydatid disease
      (fistuias, compressioni cholestasis, rupture in biliary tree). METHODS: During
      the period 1994-2003, 22 patients (12 male and 10 female, mean age 55.4 years,
      range 16-65 yrs) underwent endoscopic treatment for complications of hepatic
      hydatid disease. Indications for ERCP in 5 patients treated before surgery (Group
      A) were obstructive jaundice in ali, associated with acute cholangitis in 4 (80%)
      and acute pancreatitis in 1 (20%). In 17 patients treated after surgery (Group
      B), the indication was acute cholangitis in 6 (36%), obstructive jaundice 3
      (17%), and persistent external drainage in 8 patients (47%). OBSERVATIONS: In
      group A, ERCP detected hydatid vesicies within the bile duct in all patients. Ali
      patients underwent endoscopic sphincterotomy and clearance of the duct with no
      complications. The 8 patients in Group B with persistent external drainage had
      biliary fistulas that resolved after endoscopic treatment within 10 to 25 days
      (in 4 patients with low-flow fistula was positioned nasobiliary drain to repeat
      cholangiogram) or in 4-6 weeks (in 4 patients with high-flow fistula was
      positioned biliary endoprosthesis). In 2 of 8 patients (25%) with postoperative
      external biliary fistulas was observed choledocholitiasis (resolution with ERCP).
      Ali the 9 patients with postoperative obstructive jaundice or acute cholangitis,
      had cyst remnants obstructing the bile duct. Surgical reintervention was avoided
      in all patients in group B: all underwent endoscopic sphincterotomy and clearance
      of the bile duct without complications. After treatment, all patients remained
      asymptomatic. CONCLUSION: Endoscopic sphincterotomy with positioning of naso
      biliary drain or biliary endoprosthesis is a safe and effective treatment for
      preoperative and postoperative biliary complications of hepatic hydatid disease.

PMID- 15960340
TI  - Radiofrequency ablation of liver tumours with transpleurodiaphragmatic access.
AB  - Radiofrequency thermoablation (RFA) is used to treat unresectable liver tumours.
      RFA is performed using an abdominal access (laparotomic, laparoscopic and
      percutaneous). A transpleurodiaphragmatic approach has recently been proposed,
      particularly for the treatment of tumours which are placed near to inferior vein
      cava and hepatic veins and which are difficult to reach for an abdominal access.
      A patient with a liver metastasis of the segment VIII underwent RFA with an
      associated wedge resection of the segment VII, both were performed with a
      transthoracic access. Peri- and postoperative complications did not occurred. The
      patient was discharged on fifth postoperative day, and she is disease free after
      a follow up of 6 months. A transpleurodiaphragmatic access can be considered a
      safe and efficacy procedure to perform an RFA of a liver tumour in selected
      cases.

PMID- 15960341
TI  - [Simultaneous pancreas-kidney transplantation: a single center experience on 148
      cases].
AB  - AIM: To evaluate the outcome of simultaneous pancreas transplantation (SKPT)
      focusing on the surgical technique applied. PATIENTS AND METHODS: One hundred
      forty-eight patients were submitted to SKPT 33 with segmental pancreas with duct
      occlusion (from 1985 to 1990), 77 with whole pancreas with bladder diversion
      (from 1990 to 1998) and 38 whole pancreas with enteric diversion (29 with
      systemic and 9 with portal drainage) (from 1998 to December 2001). RESULTS:
      Patient survival was 92%, 82%, 63% at 1, 5, and 10 years respectively. Kidney
      survival was 87%, 75%, and 48% at 1, 5, 10 years. Pancreas graft survival was
      71%, 58%, and 46% at 1, 5, 10 years. In the enteric diversion group patient,
      kidney, pancreas survival at one year was 93%, 92%, and 75%. A positive effect on
      patient survival was evident in enteric diversion versus duct occlusion group (p
      = 0.03), but not versus bladder diversion group and on pancreas graft survival in
      enteric diversion versus duct occlusion group (p < 0.01). CONCLUSIONS: These data
      suggest that SKPT has become a successful intervention for patients with type I
      diabetes and end stage renal disease. Reasons for these improvements include
      improved donor and patient selection criteria, refinements in surgical technique
      and better immunosuppression.

PMID- 15960342
TI  - The treatment of chronic intestinal ischemia.
AB  - BACKGROUND AND AIMS: Due to the rarity of the condition, large and prospective
      series defining the optimal method of digestive arteries revascularization, for
      the treatment of chronic intestinal ischemia, are lacking. The aim of this
      consecutive sample clinical study was to test the hypothesis that flexible
      application of different revascularization methods, according to individual
      cases, will yield the best results in the management of chronic intestinal
      ischemia. PATIENTS AND METHODS: Eleven patients, of a mean age of 57 years,
      underwent revascularization of 11 digestive arteries for symptomatic chronic
      mesenteric occlusive disease. Eleven superior mesenteric arteries and one celiac
      axis were revascularized. The revascularization techniques included retrograde
      bypass grafting in 7 cases, antegrade bypass grafting in 2, percutaneous arterial
      angioplasty in 1, and arterial reimplantation in one case. The donor axis for
      either reimplantation or bypass grafting was the infrarenal aorta in 4 cases, an
      infrarenal Dacron graft in 4, and the celiac aorta in one case. Grafting
      materials included 5 polytetrafluoroethylene (PTFE) and 3 Dacron grafts.
      Concomitant procedures included 3 aorto-ilio-femoral grafts and one renal artery
      revascularization. Mean follow-up length was 31 months. RESULTS: There was no
      operative mortality. Cumulative survival rate was 88.9% at 36 months (SE 12.1%).
      Primary patency rate was 90% at 36 months (SE 11.6%). The symptom free rate was
      90% at 36 months (SE 11.6%). CONCLUSIONS: Direct reimplantation, antegrade and
      retrograde bypass grafting, all allow good mid-term results: the choice of the
      optimal method depends on the anatomic and general patients status. Associated
      infrarenal and renal arterial lesions can be safely treated in the same time of
      digestive revascularization. Angioplasty alone yields poor results and should be
      limited to patients at poor risk for surgery.

PMID- 15960343
TI  - [Emergency surgery for complicated colorectal cancer. Retrospective study].
AB  - INTRODUCTION: Emergency surgery for the complications of colorectal cancer poses
      a significant surgical problem with published mortality rates as hight as 25% to
      30%. We reviewed the results of the analysis and quantification of the influence
      of complications on the outcome of the patients who underwent emergency colectomy
      for colorectal cancer. MATERIALS AND METHODS: Retrospective study of the clinical
      features from, a series of 63 patients operated on from 1991 to 1997 (12% of all
      colorectal cancer operations in the same period). The correlations between
      complications and cancer stages were estimated by the KW (ANOVA method). RESULTS:
      Fifty-three patients underwent colorectal resection for intestinal occlusion
      (84%), 5 for perforation (8%) and 5 for lower gastrointestinal bleeding (8%).
      When the cancer complications were correlated to the different cancer stage at
      operation, the complications rate were 32%, 32%, and 36% in the stage II, stage
      III, and stage IV, respectively. This data was statistically significant: (KW =
      58, p = 0.0001). The overall mortality rate was 8% (5 patients) and the total
      postoperative morbity rate was 32% (21 patients). The overall 5-year, 3-year, and
      1-year survival was 47%, 48%, and 76% respectively. CONCLUSIONS: Emergency
      surgery for complicated colorectal cancer can be performed safely with low
      postoperative morbidity and mortality rate and can be advocated to realize both
      short and long-term survival rates comparable to elective surgery; the KW test
      supports the hypothesis that the a complication in the natural history of
      colorectal cancer doesn't correlate with the stage of disease.

PMID- 15960344
TI  - [Sigma's stenosis. Clinical, diagnostic and therapeutical problems].
AB  - Sigma's stenosis represent a frequent pathology, but its very difficult to have a
      pre-operatory diagnosis about the nature of these stenosis, not withstanding the
      introduction of more sophisticated instruments of diagnosis. In this work we
      present 9 cases of sigma stenosis; some of these with a common etiology and other
      very interesting for their rare and unusual origins. The patients were underwent
      to a different timing of diagnosis and therapy based on clinical history and
      diagnostic hypotheses; our experiences demonstrate that the clinical intuition is
      really useful for a correct diagnosis in the patients with a sigma's stenosis and
      consequently, in order to plan the correct therapy.

PMID- 15960345
TI  - [Early diagnosis importance for a correct surgical treatment of PAES (popliteal
      artery entrapment syndrome)].
AB  - Popliteal artery entrapment syndrome (PAES) is an uncommon pathological entity,
      caused by segmental popliteal artery compression by the surrounding myofascial
      structures. Clinical symptoms may appear acutely, with temporary ischaemic
      attacks, or chronically, with concerned calf claudicatio intermittens and for 30%
      are bilateral. Diagnosis, besides being based on clinical objectivity (acute and
      deep pain to the struck limb, mainly during active plantar hyperextension) and
      history-taking (subject-age and lack of atherosclerosis), is based on
      ultrasonographic (eco-color Doppler of the aortic-iliac-femural-popliteal trunks,
      tensiometric Doppler), angio-RM, angio-CT scan and dynamic angiographic exams.
      Treatment, essentially, is surgical by simple freeing of the popliteal artery
      from surrounding myofascial structures or by autologous vein (saphenous v.)
      interposition grafting and patching, or bypass without vessel resection. About
      clinical case reported by the authors, 44-years female with left calf acute pain
      symptoms, cold skin by the thermo-touch, hypo-paraesthesia with fifth toe
      cyanosis and walking inability, surgical treatment, because of precox diagnosis,
      consisted of simple cut of myofibrous shoot starting from medial head of the left
      gastrocnemious muscle and compressing popliteal artery, with clinical chart
      complete resolution.

PMID- 15960346
TI  - [The meshes of polypropylene in emergency surgery for strangulated hernias and
      incisional hernias].
AB  - INTRODUCTION: The Authors present their experience on the use of meshes of
      polypropylene in septic surgery of the abdominal wall defects. MATERIALS AND
      METHODS: From April 1999 to October 2003, 23 patients underwent intestinal
      resection (20 small intestine, 3 large intestine) for ischemic necrosis
      strangulation caused by defects in the abdominal wall (inguinal hernia 8, crural
      hernia 4, umbilical hernia 3, post-incisional hernia under umbilicus 3, post
      incisional hernia epigastric 3, giant post-incisional hernia 2). RESULTS: No
      patient died and the removal of the mesh was never required in cases of infection
      of the surgical wound; 2 surgical wounds festered, with the reopening of the
      cutaneous wound and showing of the prosthesis, 5 hygromas were all treated in a
      conservative way. DISCUSSION: The macroporous structure of the meshes of
      polypropylene, with pores of diameter larger than 70 microns, allows contact
      among the bacteria, which measure one micron in diameter, and the cells of the
      immune system, granulocytes and macrophages, with a diameter of 15-20 microns,
      allowing the recovery from infections, and determining an high resistance rate to
      infections. CONCLUSIONS: Polypropylene prostheses, thanks to their macroporous
      structure, are sufficiently resistant to infections and therefore may be safely
      used in the surgery of the defects of the abdominal wall, when, following
      ischemic necrosis, an intestinal resection is necessary.

PMID- 15960347
TI  - Resected squamous cell carcinoma of the lung infiltrating thoracic aorta: the
      endoprosthetic option--case report.
AB  - The introduction of endo-aortic prosthesis as protection of the vascular wall
      from selective adjuvant radiotherapy on microscopically aortic residual disease
      following left upper lobectomy for squamous carcinoma of the lung is suggested by
      the authors.

PMID- 15960348
TI  - [Ruptured aortic aneurysm presenting as acute abdomen: particular case report].
AB  - AIM: Ruptured aortic aneurysm can be a cause of acute abdomen. Nowadays using
      modern diagnostic techniques diagnosis is very easy. We report a particular case
      of a misdiagnosed ruptured aortic aneurysm. CASE REPORT: Man 65 y.o. admitted to
      hospital for abdominal pain and stipsis. After 1 week he developed acute abdomen
      with muscular rigidity and mild acute anemia. Few days before contrast studies
      showed a sigmoid diverticular disease. At laparotomy a ruptured aortic aneurysm
      sealed from retroperitoneal fascia and extended to abdominal walls up to rectus
      abdominis muscles was found. CONCLUSIONS: In case of acute abdomen with muscular
      rigidity and acute anemia the diagnosis of rectus abdominis muscles hematoma
      caused by ruptured aortic aneurysm must be considered.

PMID- 15960350
TI  - The surgical treatment of ilio-femoral venous obstruction.
AB  - METHODS: A series of 9 patients of a mean age of 48 years, operated on for
      compression of the ilio-femoral venous axis is reported. The cause of obstruction
      was external compression in 3 cases, a retroperitoneal sarcoma in 1 case, and an
      infrarenal aortic aneurysm in 2. Two patients presented with a Cockett's
      syndrome, 3 with a chronic ilio-femoral thrombosis, and one with a post-traumatic
      segmentary stenosis. Treatment consisted in a resection/Dacron grafting of 2
      infrarenal aortic aneurysms, one femoro-caval bypass graft, 2 transpositions of
      the right common iliac artery in the left hypogastric artery for Cockett's
      syndrome, 3 Palma's operations for chronic thrombosis, and one internal jugular
      vein interposition for segmentary stenosis. RESULTS: There were no postoperative
      deaths and no early thromboses of venous reconstructions performed. All the
      patients were relieved of symptoms during the follow-up period, whose mean length
      was 38 months. CONCLUSION: The cause of venous obstruction and the presence of
      symptoms which are resistant to medical treatment are the main indications to
      ilio-femoral venous revascularization. The choice of the optimal treatment in
      each single case yields satisfactory results.

PMID- 15960349
TI  - Acute appendicitis or something else? A case report of cecal endometriosis in
      emergency setting.
AB  - Large Bowel is not uncommonly involved by extra pelvic endometriosis, however
      cecal localization is the lowest reported in literature; the differential
      diagnosis of intestinal endometriosis remains difficult, especially in those
      patients who underwent surgery in emergency setting. The Authors report a case of
      cecal endometriosis, operated on the basis of clinical signs of surgical abdomen.
      At laparotomy macroscopic appearance of the cecal lesion, suggesting a neoplastic
      mass, induced the equip to perform a right emicolectomy. The Authors discuss the
      clinical features and the role of surgery in management of extra pelvic
      endometriosis in emergency setting, in the light of the newest advances in
      medical treatment.

PMID- 15960351
TI  - Management of colorectal emergencies: percutaneous abscess drainage.
AB  - Pelvic abscesses represent the most frequent complications of colorectal surgery.
      Percutaneous CT or US guided drainage can be an alternative to surgical drainage
      that is associated to a significant mortality rate. In the current study results
      of PAD, performed in 39 patients with pelvic or abdominopelvic abscesses were
      reviewed in order to evaluate reliability of such procedure. Major part of the
      collections 33/39 (85%) developed after resective colorectal surgery, and 20/39
      (51%) were associated to anastomotic fistula; 22/39 (56%) were poorly defined;
      16/39 (41%) were multiloculated; 16/39 (41%) had a stool contamination, 23/39
      (58%) were greater than 10 cm; 14/39 (35%) were multiple. Thirty-five patients
      (89.7%) healed, despite high number of complex abscesses and complete resolution
      of sepsis was achieved in 5.1 +/- 2.9 days. CT proved to be the most reliable
      tool in assessing distinctive features of collections as well as in identifying
      the best route for drainage. Adequate size of the catheter was essential to get
      an effective drainage. In particular, large sized catheter (> 20 Fr) had to be
      used to drain collections associated to anastomotic fistulas with stool
      contamination. In four elderly neoplastic patients with chronic illnesses (10%),
      only a single small sized catheter could be positioned, because of patients poor
      compliance and PAD was inaffective. Nevertheless even those patients got a
      partial resolution of the sepsis and their general conditions markedly improved,
      so that they were able to underwent successful surgical drainage. In conclusion
      PAD is a safe and reliable tool that can be employed as an alternative to
      surgical drainage at least as first measure, even if complex pelvic abscesses are
      found.

PMID- 15960352
TI  - [Surprise in the hernia sac: the intrasaccular tumor of the sigma].
AB  - In this report we define the terms of saccular, extra-saccular and intrasaccular
      tumor and present a rare case of intrasaccular tumor of the colon; it is remarked
      a careful clinical examination of patients with inguinal hernias to find a colon
      tumor; diagnosis in emergency is intra-operative. Two therapeutics options are
      possible: the simultaneous treatment or the delayed resolution.

PMID- 15960354
TI  - Surgical treatment of haemorrhoidal disease: a survey of the regional area of
      Campania in Italy.
AB  - INTRODUCTION: In order to monitor the common practice regarding the surgical
      treatment of haemorrhoidal disease in Campania, a region in the South of Italy, a
      survey amongst one hundred specialists in general surgery and members of the
      Neapolitan Surgery Association (S.Na.C.) was carried out. MATERIALS AND METHODS:
      The survey was carried out through a 13-items questionnaire sent to 100 General
      Surgeons working in Campania. The survey sample was chosen randomly from the
      S.Na.C. members. Participants were given two weeks to fill in and return the
      questionnaire. RESULTS: The survey, was developed to obtain a "picture" of the
      current situation and revealed some interesting results: the procedure preferred
      was the Milligan and Morgan Haemorrhoidectomy (MMH) being used in 41% of the
      cases, whilst stapled haemorrhoidopexy (SH) was carried out only in 19% of the
      cases and 44.4% of the surgeons never carried even one. With regard to
      postoperative complications, bleeding was the most common after SH which occurred
      in 10 out of 260 cases (3.8%), whereas anal pain was the most common after MMH
      (179%). DISCUSSION: In keeping with the literature the analysis shows that,
      although fairly good results with low complication rates are reported with SH, it
      is still not widely accepted and is performed in only 19% of the patients in our
      Regional area.

PMID- 15960353
TI  - Treatment of pilonidal disease in short-stay surgery: personal method.
AB  - HYPOTHESIS: We state that our personal method constitued by excision and primary
      closure in the treatment of pilonidal sinus, is able to obtain a low rate of
      recurrence and a fast return to work. PATIENTS AND METHODS: Our report has been
      conducted on 315 patients. Excision and primary closure in the treatment of
      pilonidal sinus by local-regional anesthesia. The patients have been discharged
      on second day. RESULTS: We have not had intraoperative complication; about
      morbilita there have been 4% of seromas treated conservatively. CONCLUSIONS: With
      this personal method we have obtained very good results, in short and long time,
      with less of recurrences and fast return to work.

PMID- 15960355
TI  - [Post-thyroidectomy hypocalcemia].
AB  - INTRODUCTION: The correlation between hypocalcemia and total thyroidectomy could
      be correlated to the influence practice from the TSH hormone on the thyroid C
      cells, in fact in conditions of hyperthyroidism the low values of the thyrotropin
      is correlated to a reduction of the plasmatic concentration of calcitonin and
      consequently of calcemia. of our study is verify the incidence of the
      hypocalcemia post-tyroidectomy and appraise the effectiveness of the
      pharmacological treatment with calcium salts and possibly D vitamin. MATERIALS
      AND METHODS: Of the 432 operated patients, 348 has stayed subjected to total
      thyroidectomy and 84 to loboistmusectomy. In none case subjected to
      emityroidectomy has been verified a hypocalcemia in the post-operative and in 67
      cases in which we have administered pre-operative calcium salts orally, calcemia
      has sustained within acceptable values. RESULTS: Our experience only 1'11.2% of
      the patients subjected to total thyroidectomy they have presented a reduction of
      the calcemia to the of under of the 7.10 mg/dl and they have stayed subjected
      medical therapy with calcium salts in ev in the symptomatic forms, and to oral
      therapy in patients absent symptoms, while in two cases is not been practiced any
      therapy because the symptomatology has disappeared spontaneously DISCUSSION:
      Syndrome hypocalcemica has determined from the deficit-also transitory
      parathyroid glands, from the action of the calcitonin (it favors the amassing of
      the calcium in to bon), and from a reduced bony reserve of calcium. In fact in
      those patients operated for a euthyroid goitre or for thyroid tumor the saving of
      the parathyroid glands avoids the outbreak of hypocalcemia (7, 8). Therefore the
      physio-pathological mechanism responsible of symptoms (excluded the medical
      causes: pharmacological treatments with steroid, oral conraceptives, diuretics,
      salts of lithium, oral antacid and diazepam) (9) also not being still of the all
      known, it would have his primum movens in the parathyroid glands ischemia.
      CONCLUSIONS: The precocious evaluation of the calcemia in the period post
      operative is useful to discern the patients that will require of a
      pharmacological treatment of support, so that avoid of the serious and permanent
      damages to the varied organs.

PMID- 15960356
TI  - [Artificial nutrition in inflammatory bowel disease].
AB  - Malnutrition is often a major clinical problem in patients affected by IBD.
      Assessment of nutritional status should be routinely carried out in these
      patients and, in case of severe malnutrition, artificial nutrition should be
      used. In ulcerative colitis and in Crohn disease localized to colonic segments
      both Parenteral Nutrition (PN) and Enteral Nutrition (EN) have similar results as
      support treatments but they have no primary therapeutic effects and then they are
      indicated only in case of severe malnutrition and/or when a surgical procedure is
      planned. Some theoretical advantages derived from supplementation of short chain
      fatty acids and omega3-series is still debated. More evident are the advantages
      of nutritional support in Crohn enteritis. Both PN and EN have a role as a
      primary therapy capable to induce remission although these results are not
      prolonged in time when nutrition is not associated with pharmacological
      treatments. Experiments of pharmaco-nutrition with glutamine and fish fatty acid
      have to be validated in the clinical practice. In case of integrity of the small
      bowel and tolerance of the patient, EN is preferable to PN for its lower costs
      and reduced related complications. PN is still indicated in more severe cases or
      in acute phase when the need of restoring rapidly the hydroelectrolitic and
      nitrogen/caloric balance prevails.

PMID- 15960357
TI  - Radiofrequency thermal ablation of hepatocellular carcinoma: our five year
      experience.
AB  - PURPOSE: We describe our experience in the multimodal treatment of HCC patients
      both using the PRFTA and IRFTA treatment associated or not with hepatic
      resection, valuating the feasibility, the complication, length of hospital stay
      and survival rate of selected HCC patients. MATERIALS AND METHODS: Between March
      1998 and January 2004, 53 HCC patients undergoing PRFTA and IRFTA treatment. We
      describe 41 patients with monofocal disease and 12 patients with multifocal
      disease: in this last group 7 patients had unilobar involvement while 5 patients
      had multilobar tumour. RESULTS: We reported patients underwent RFTA because not
      candidates to surgical procedures and patients underwent liver resection and open
      radiofrequency treatment associated. We successfully used percutaneous and
      intraoperative approach being the last one significantly advantageous in lesions
      greater than 5 cm, multiple bilobar tumours and tumours close to the hilum and
      major vessels: the laparotomic approach permitted the temporary occlusion of the
      vascular inflow allowing Pringle manoeuvre. DISCUSSION: Hepatocarcinoma still
      represent one of the major causes of cancer related death worldwide. Systemic
      therapeutic agents and locoregional agents are rarely correlated to complete
      response and usually associated to high toxicities: the potentially curative or
      palliative benefit of RFTA in non surgical candidates improve overall patients
      survival significally better then the chemotherapy regimens. CONCLUSION: RFTA
      appears to have several advantages, which also include a reducing in morbidity, a
      shortening of the hospital stay and good response to patients requirement in term
      of enduring pain.

PMID- 15960359
TI  - Right colectomy for cancer: validity of laparoscopic approach.
AB  - AIM: Laaroscopic assisted right colectomy for carcinoma is a procedure with
      demonstrated feasibility. We want to evaluate the advantages. MATERIAL: In the
      period 1999/2002 we have executed 7 laparoscopic right colectomy for carcinoma.
      We have compared the results with one group of 10 patients traditionally operated
      in the period 1998/2002. In both groups the oncologic staging was almost the
      same. RESULTS: Immediate results: operative time was 240' for laparoscopy vs.
      150' for open operation; no anastomotic dehiscence for laparoscopy vs. 1/10 for
      open; no bronchopulmonary-thrombotic complications for laparoscopy vs. 2/10 for
      open, but there was 1/7 wound infection for laparoscopy vs. 1/10 for open; the
      return to the mobilization and normal diet was 3 days for laparoscopy vs. 7 days
      for open; the postoperative stay was 7 days for laparoscopy vs. 12 days for open.
      DISCUSSION: The two procedures did not condition differences neither in the
      extension of the resection and of the lymphectomy nor a different incidence of
      the anastomosis dehiscences. Differences were noted, in the operative time, in a
      more precocious mobilization with a minor use of analgesics, in a more rapid
      renewal of peristalsis and of feeding with a lower postoperative stay. These
      advantages are remarkable in our study, by reducing the postoperative morbidity.
      The very brief follow-up of almost 6 months, did not show a relapse of the
      disease in patients of both series. CONCLUSION: In our experience, laparoscopic
      assisted right colectomy confirmed evident advantages in the immediate
      postoperative period for the treatment of the colonic cancer.

PMID- 15960358
TI  - ["Rendez-vous" technique for palliation of neoplastic jaundice: personal
      experience].
AB  - INTRODUCTION: "Rendez-vous" technique (RV) assume contemporaneous percutaneous
      transhepatic choledochal drainage (PTCD) and endoscopic (ERCP) approach to make
      easier biliary cannulation when it fails for anatomic, neoplastic or iatrogenic
      causes, in subject unresectable at presentation ("not fit for surgery").
      MATERIALS AND METHODS: Over a 3 years period 618 ERCP were performed in the
      Service of Digestive Endoscopy in Section of General and Thoracic Surgery, 59 of
      whom (9%) failed for non-visualization of ampulla of Vater (25%),
      intradiverticular ampulla (54%) or anatomic defects (21%). Were attempted 44 pre
      cut: 14 failed (close biliary stricture), and we proceed to RV. RESULTS: 11/14
      (79%) RV were successful (successful stent insertion was defined as passage of
      the stent across the stricture) and 3 failure (21%) occurred in close biliary
      malignant obstruction even to percutaneous transhepatic approach. Only in 28%
      were registered minor complications (2 post-procedure fever, 1 papillary bleeding
      post PTE, 1 case mild acute pancreatitis). No mortality procedure related was
      registered and was not necessary to recur to surgery. CONCLUSIONS: RV is very
      useful in case of difficult cannulation of biliary tree and after failure of pre
      cut. US-guided PTC is easy to perform, with low incidence of complications. Every
      well experienced team who works on bilio-pancreatic pathologies may recurs to
      this technique: even if not much utilized, RV can solves complex cases of biliary
      stricture.

PMID- 15960360
TI  - [Stapled hemorrhoidopexy in the treatment of hemorroidal prolapse].
AB  - In the treatment of hemorroidal prolapse, stapled hemorrhoidopexy, according to
      the Longo's technique, represents an innovative and interesting procedure. The
      Authors consider own experience in the years 2001-2002, estimating preliminary
      results in the treatment of 50 patients affected by hemorrhoidal disease
      classified as III-IV grade, associated with mucosal prolapse, rectocystocele in 5
      cases, anal fissures in 6 and hyperplastic polyp in 1. The patients were
      submitted to mucosal prolapsectomy with mechanical stapler (PPH 01-33 Ethicon),
      applying haemostatic stitch on suture line, apart from intraoperative bleeding,
      associated to closed anal sphincterotomy in 6 cases, and resection of anal
      hyperplasic polyp in 1. In 5 cases of rectocystocele a Burch's culposuspension
      was associated to a stapled transanal rectal resection (STARR). After 3 and 12
      months the Authors performed ano-rectoscopy, anal manometry and defecography.
      Mean operative time was 45 minutes (range 20'-130') and mean hospital stay was 3
      days (range 2-6 days). In the early postoperative course urinary ritention in 4
      cases, treated with temporary catheterization in 3 and permanent for 72 hours in
      1, was observed. Only 1 patient, was reoperated in day-surgery and with loco
      regional anesthesia for residual fibrous hemorroid. Bleeding, severe pain, anal
      stenosis, impairment of continence were not observed. According to the Literature
      data, our experience confirm that mucoprolapsectomy represents an innovative,
      safe, simple and definitive operation in the treatment of hemorrhoids disease. In
      case of rectal prolapse associated to external fibrous hemorroids, a combined
      surgical treatment is requested in order to achieve better results.

PMID- 15960361
TI  - [Hurthle cell neoplasm: our experience].
AB  - Hurthle cell neoplasm is a rare form of thyroid tumors, comprising from 1.5% to
      10% of all tumors. Hurthle cell nodules are clinically indistinguishable from
      other nodular thyroid diseases. The histologic features of Hurthle cell neoplasm
      don't allow us to exactly distinguish benign nodules from malignant ones.
      Accurate histologic valutation is possible and necessary for a correct diagnosis
      and therapy of Hurthle cell tumors. The adenomas usually exhibit a follicular
      pattern; the carcinomas include a subset of Hurthle cell tumors with different
      biological behavior, including malignant follicular variants and papillary ones.
      The authors are in favour of total thyroidectomy for carcinomas and lobectomy
      plus isthectomy for adenomas; in case of carcinomas, the lymphadenectomy reduces
      the incidence of local relapse and is necessary in case of lymphnode involvement.
      Adjuvant radiation therapy is successful in preventing recurrences, in
      symptomatic metastates as palliative therapy and control recurrence of advanced
      resected tumors.

PMID- 15960362
TI  - Male breast cancer: report of 2 cases and review of the literature.
AB  - Male breast cancer is rare and accounts for 1% of all breast cancers. The authors
      report two cases of male breast cancer at Stage III and review the literature. A
      Madden mastectomy with axillary clearance was performed. Patients were given
      adjuvant chemotherapy and started on tamoxifen. At one year follow-up the
      patients are alive and free from disease. Modified radical mastectomy is the
      preferred surgical approach for localized disease. Adjuvant hormonal therapy with
      tamoxifen is recommended as first-line treatment. Adjuvant chemotherapy has a
      role in node-positive cancer and locally advanced disease. Men should be made
      more aware of the disease and multicentric clinical trials encouraged to ensure
      an appropriate treatment on the basis of prospectively collected data.

PMID- 15960364
TI  - [Giant adrenal myelolipoma: a case report and review of the literature].
AB  - Adrenal myelolipoma is a rare nonfunctioning tumor consisting histologically of
      an admixture of adipose tissue and extramedullary hemopoietic elements within the
      adrenal glands. Most of these lesions are 5 small and asymptomatic, but there are
      also giant ones, associated with endocrine disorders. These tumors are mostly
      detected incidentally by imaging. The increasing number of incidentally
      discovered adrenal myelolipomas arise the question of appropriate treatment
      modalities. The authors report a case of giant myelolipoma associated with
      lithiasic cholecystitis and discuss different imaging and terapeutic aspects.

PMID- 15960363
TI  - [Idiopathic ischaemic infarction of the stomach. Case report].
AB  - Idiopathic ischaemic infarction of the stomach is an extremely rare condition
      since only 2 other cases have been published in the Literature so far. The
      Authors report a case of such entity on a 75 year old male patient, admitted from
      the accident and emergency department because of a upper digestive tract
      haemorrhage with clinical signs of hypovolemic shock. The patient subsequently
      underwent an upper gastro-intestinal endoscopy that suspected an ulcerated
      gastric neoplasm. The patient therefore underwent a total gastrectomy and was
      discharged home on p.o. day X. The pathology report showed an Ischaemic
      infarction of gastric mucosal tissue with pomphoid Oedema of submucosal layer.
      Ulcerative superficial necrosis with venous haemorragic swarm and focal acute
      pseudomembranous inflammation. Not neoplastic features. Etiopathogenetic,
      pathophisiologic ipoteses and clinical implication of Idiopathic ischaemic
      infarction of the stomach are discussed.

PMID- 15960366
TI  - [Acute appendicitis associated to "serrated" adenoma: a case report].
AB  - The authors describe a case of acute appendicitis associated "serrated" adenoma
      (SA). to the histological finding of a SA is a colorectal pre-cancerous lesion
      which presents the morphological and architectural characteristics of hyperplasic
      polyps, combined with aspects of adenomatous dysplasia. SA can eventually evolve
      into a malignant cancer, similarly to classic adenomatous polyps. Clinical and
      pathological aspects of this lesion are hereby analysed, with respect to recent
      Literature data.

PMID- 15960365
TI  - Endocrine function in abetalipoproteinemia: a study of a female patient of Greek
      origin.
AB  - AIM: To investigate the pituary, genitalia, adrenal, thyroid, parathyroid and
      pancreatic endocrine function of a female patient aged 37 with
      abetalipoproteinemia at the time of diagnosis and 5 years thereafter (after
      application of a modified diet). SUBJECT-METHODS: Serum concentrations of
      cortisol, A4, ACTH, aldosteron, renin, dehydroepiandrosterone sulfate (DHEA-5),
      progesterone, 17-OH progesterone, testosterone, SH13G, estradiol, luteinizing
      hormone, follicle stimulating hormone, T3, T4, TSH, FT3, FT4, parathormone,
      osteocalcin, prolactin, proinsuline, insulin, glucagon, somatomedin-C (Insulin
      like Growth Factor-1, IGF-1), IG171-13P3, 25 (OH) Vitamin D3 and 1-25 (OH) 2
      Vitamin D3, were measured by radioimmunoassay. Synactlien test, and 24-hour urine
      cortisol, were also estimated. Serum leptin estimation was carried-out using a
      sensitive enzymatic technique. Ionized part of serum calcium was measured by the
      use of a special machine (CORNING), while bone alkaline phosphatase was measured
      by radioimmunoassay. RESULTS: Serum progesterone and 17-OH-progesterone were
      reduced in both examinations. Estimation of serum progesterone performed on the
      21th day of the menstrual cycle revealed again values below the lowest normal
      limit. Serum prolactin was increased both in rest and during movement. The levels
      of both, somatomedin-C (IGF-1) and leptin were below the lowest normal limit.
      Despite normal serum parathormone, serum-ionized calcium and 25-OH vitamin D were
      low, while serum bone alkaline phosphatase was increased. Serum proinsulin was
      increased, and serum insulin was low. Serum thyroid hormone, glucagon,
      parathormone, FSH, LH, ACTH, testosterone, estradiol and SH13G were normal. The
      hormonal profile of the patient estimated 5 years later did not differ
      substantially suggesting that the metabolic improvement due to the adoption of
      the modified diet had not any significant impact on it. CONCLUSION: Female
      patients with abetalipoproteinernia have reduced production of progesterone by
      the corpus luteum and slightly abnormal bone metabolism. The reduced production
      of progesterone is probably due to the low levels of serum LDL and cholesterol,
      while reduced serum levels of Leptin and IG17-1 are probably due to the
      impairment nutritional status. The adoption of a modified diet does not alter the
      hormonal profile significantly.

PMID- 15960367
TI  - [Tardive cecal metastasis from ovarian cancer: a case report].
AB  - Intestinal insolvement is a frequent sequela of metastatic ovarian cancer may be
      syncronous or following ovaric resection, after several years of disease free
      condition. The authors herein describe a clinical report of a case of cecal
      metastatic neoplasm due to ovarian cancer treated with surgical resection 24
      years before.

PMID- 15960368
TI  - [Intestinal enterolithiasis].
AB  - We present a case report of a patient affected by chronic ileitis re-made acute
      and in which we found some entheroliths; they wern't not bezoars. We remarked the
      importance in bowel diseases in which are stasis or ipomotility like the Crohns
      disease. Sometimes they are responsible of subsequent complications like
      obstructions, hemorrages, perforations and so their presence must be considered
      by important diagnostic implications.

PMID- 15960369
TI  - [Mesenteric fibromatosis: a case report].
AB  - Authors report a case of mesenteric fibromatosis, not associated to familial
      adenomatous polyposis or Gardner's syndrome. It is generally considered benign
      lesion without metastases, though local recurrences are very frequent. No
      symptoms are usually referred until compression of the surrounding organs, due to
      the mass growing, takes place. Surgical therapy is considered treatment of
      choice.

PMID- 15960370
TI  - 'Are we there yet?'.

PMID- 15960371
TI  - White House asks Congress to take a closer look at long-term care.

PMID- 15960372
TI  - Consumers' right-to-know: legislative, regulatory efforts gaining momentum.

PMID- 15960373
TI  - Healthy response to government long-term care awareness pilot.

PMID- 15960375
TI  - Revolutionizing health care: creating a system that works for every American.

PMID- 15960374
TI  - The future of health care arbitration in America.

PMID- 15960376
TI  - Putting consumers in the driver's seat?

PMID- 15960377
TI  - Driving positive change through programs that reward quality performance.

PMID- 15960378
TI  - Advancing the health information technology initiative, ahead of schedule.
      Interview by Ed Rabinowitz.

PMID- 15960379
TI  - Choosing between consumer-driven accounts.

PMID- 15960380
TI  - The results are in: preliminary data points to success of consumer-directed
      plans.

PMID- 15960381
TI  - Decision support tools empower consumers.

PMID- 15960382
TI  - Intelligent integration: the value of coordinating disability and medical
      coverage.

PMID- 15960383
TI  - Stopping chronic illness before it starts.

PMID- 15960384
TI  - Service-oriented architecture: a critical technology component to support
      consumer-driven health care.

PMID- 15960385
TI  - On mentoring and magnetism.

PMID- 15960386
TI  - The art of expressive nursing. An interview with hospice nurse Christine Hall,
      RN, CHPN. Interview by James D Henry.

PMID- 15960387
TI  - Prevention and management of oral mucositis for an outpatient oncology setting.

PMID- 15960390
TI  - Laugh until you die.

PMID- 15960389
TI  - ANCC certification: personal and professional affirmation.
AB  - Certification is sited as one way of demonstrating competency. There are
      currently many reasons for pursuing certification, including personal
      satisfaction, validation of one's ability to effectively fulfill leadership
      roles, and to augment organizational efforts to become an ANCC Magnet Hospital.
      Regardless of the reason, achieving certification requires preparation and
      completion of an examination. Cary (2001) notes there are 4 avenues through which
      certification status can be recognized: public acknowledgement, financial
      compensation, career advancement, and retention. Colleagues who complete this
      process desire and deserve to be acknowledged and affirmed. Do you recognize
      colleagues in the attached list of ANCC certified nurses? If yes, take a minute
      and congratulate them on their accomplishment.

PMID- 15960391
TI  - Laminin alpha3 LG4 module induces keratinocyte migration: involvement of matrix
      metalloproteinase-9.
AB  - Laminin alpha3 chain, a functionally key subunit of laminin-5, contains a large
      globular module (G module) which consists of a tandem repeat of five homologous
      LG modules (LG1-5). We previously demonstrated that the LG4 module of laminin
      alpha3 chain (alpha3 LG4) induces a matrix metalloproteinase-1 (MMP-1) expression
      through the interaction with syndecans leading to MAPK activation/IL-1beta
      expression signaling loop (Utani et al., J. Biol. Chem. 278, 34483-34490, 2003).
      Here, we show that a recombinant alpha3 LG4 and synthetic peptides containing
      syndecan binding motif induced a cell motility and a MMP-9 expression in
      ketarinocytes. The synthetic peptide (A3G756)-induced cell migration and MMP-9
      upregulation were inhibited by each application of a heparin and an IL-1 receptor
      antagonist (IL-1RA), suggesting the involvement of syndecans and IL-1beta
      autocrine. Furthermore, the A3G756-induced cell motility was inhibited by an MMP
      9 inhibitor and a neutralizing antibody of MMP-9, indicating induced cell
      motility was dependent on an MMP-9 activity. Taken these together, laminin-5
      alpha3 LG4 module may play an important role in re-epithelialization at tissue
      remodeling.

PMID- 15960392
TI  - Protein tyrosine phosphatase LMW-PTP exhibits distinct roles between vascular
      endothelial and smooth muscle cells.
AB  - The present study examined the cellular functions of low-molecular-weight protein
      tyrosine phosphatase (LMW-PTP), which consists of two active isoforms IF-1 and IF
      2, in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), focusing
      on cell growth and migration. We transduced recombinant IF-1 and IF-2, and
      ribozyme targeting both isoforms using an adenovirus vector in these cells. We
      detected the expression of IF-1 and IF-2 in both types of cells. IF-1 as well as
      IF-2 inhibited PDGF-induced DNA synthesis and migration in VSMCs. In contrast,
      both isoforms enhanced lysophosphatidic acid-stimulated cell migration without
      change in DNA synthesis in ECs. Whereas there is a report indicating that
      reactive oxygen species-dependent inactivation of LMW-PTP regulates actin
      cytoskeleton reorganization during cell spreading and migration, the isoforms
      conversely suppressed the PDGF-induced H2O2 generation with subsequent decrease
      in the p38 activity in VSMCs. Catalytically inactive LMW-PTP exerted the opposite
      and similar effects to the wild type in ECs and in VSMCs, respectively,
      suggesting that substrates for the phosphatase differ between these cells.
      Moreover, high concentrations of glucose suppressed the expression of LMW-PTP in
      both cells. These data suggest that LMW-PTP negatively regulates the pathogenesis
      of atherosclerosis and that glucose-dependent suppression of LMW-PTP expression
      may promote the development of atherosclerosis in diabetics.

PMID- 15960395
TI  - Muscle relaxants--the early history.

PMID- 15960393
TI  - Species differences in angiotensin II generation and degradation by mast cell
      chymases.
AB  - Although chymases are known to exhibit species differences in regard to
      angiotensin (Ang) II generation and degradation, their properties have never been
      compared under the same experimental conditions. We analyzed the processing of
      Ang I by chymases of a variety of species (human chymase, dog chymase, hamster
      chymase-1, rat mast cell protease-1 [rMCP-1], mouse mast cell protease-4 [mMCP
      4]) at physiological ionic strength and under neutral pH conditions. Human
      chymase generated Ang II from Ang I without further degradation, whereas the
      chymases of other species generated Ang II, followed by degradation at the Tyr4
      Ile5 site in a time-dependent manner. Kinetic analysis showed that in terms of
      Ang II generating activity (analyzed by cleavage of the Phe8-His9 bond using the
      model peptide Ang(5-10), Ile5-His6-Pro7-Phe8-His9-Leu10), the chymases ranked as
      follows: dog > human > hamster > mouse > rat (kcat/Km: 18, 11, 0.69, 0.059, 0.030
      microM-1min-1), and that in terms of Ang II degrading activity (i.e., cleavage of
      the Tyr4-Ile5 bond of Ang II), the order was hamster > rat > mouse > dog
      (kcat/Km: 5.4, 4.8, 0.39, 0.29 microM-lmin-1). These results suggest species
      differences in the contribution of chymases to local Ang II generation and
      degradation.

PMID- 15960394
TI  - Comparison of ELISA-based tyrosine kinase assays for screening EGFR inhibitors.
AB  - Receptor tyrosine kinases (PTKs) play key roles in the pathogenesis of numerous
      human diseases, including cancer, and therefore PTK inhibitors are currently
      under intense investigation as potential drug candidates. PTK inhibitor screening
      data are, however, poorly comparable because of the different assay technologies
      used. Here we report a comparison of ELISA-based assays for screening epidermal
      growth factor receptor (EGFR) tyrosine kinase (TK) inhibitory compound libraries
      to study interassay variations. All assays were based on the same protocol,
      except for the source of EGFR-TK enzymes. In the first protocol, the enzyme was
      isolated from A431 cells without affinity purification. In the second protocol,
      commercial EGFR-TK (Sigma) isolated from A431 cells by affinity-purification was
      employed. In the third protocol, an enzyme preparation obtained from a
      recombinant (Baculovirus transfected Sf9 cells) expression system was used. All
      assays employed the synthetic peptide substrate poly-(Glu,Tyr)l:4 and an ELISA
      based system to detect phosphorylated tyrosine residues by a monoclonal antibody.
      We observed significant differences in both the activity of the enzymes and in
      the EGFR-TK inhibitory effect of our reference compound PD153035. The differences
      were significant in case of A431 cell lysate compared to affinity purified EGFR
      TKs derived from either A431 cells or Baculovirus transfected Sf9 cells, whereas
      the latter two showed comparable results. Our data suggest that differences in
      terms of interassay variation are not related to the source of the enzyme but to
      its purity; changes in the mode of detection can markedly influence the
      reproducibility of results. In conclusion, normalization of the EGFR activity
      used for inhibitor screening and standardization of detection methods enable safe
      comparison of data.

PMID- 15960396
TI  - Role of recombinant activated factor VII in the management of life-threatening
      coagulopathic bleeding.

PMID- 15960397
TI  - Substance abuse a decade on: so little and so far.

PMID- 15960398
TI  - The pregnant trauma patient.
AB  - Trauma is the leading non-obstetric cause of maternal death. Optimal management
      of the pregnant trauma patient requires a multidisciplinary approach. The
      anaesthetist and critical care physician play a pivotal role in the entire
      continuum of fetomaternal care, from initial assessment, resuscitation and
      intraoperative management, to postoperative care that often involves critical
      care support and patient transfer. Primary goals are aggressive resuscitation of
      the mother and maintenance of uteroplacental perfusion and fetal oxygenation by
      the avoidance of hypoxia, hypotension, hypocapnia, acidosis and hypothermia.
      Recognizing and understanding the mechanisms of injury, the factors that may
      predict fetal outcome, and the pathophysiological changes that can result from
      trauma, will allow early identification and treatment of fetomaternal injury.
      This in turn should improve morbidity and mortality. A framework for the acute
      care of the pregnant trauma patient is presented.

PMID- 15960399
TI  - Serotonin syndrome and the anaesthetist.
AB  - Serotonin syndrome results from excessive activation of serotonin (5
      hydroxytryptamine; 5-HT) receptors in the nervous system, on the surface of
      platelets, and on the vascular endothelium. The clinical manifestations are a
      triad of altered conscious state, autonomic dysfunction, and neuromuscular
      excitability. Clinical diagnostic criteria remain poorly defined and unvalidated,
      and there are no available investigations to confirm the diagnosis. The syndrome
      is caused by the administration of one or more drugs possessing serotonergic
      activity. Severe forms of the syndrome usually result from overdose, but can be
      induced by monotherapy. The exact incidence of serotonin syndrome remains
      unknown, but is likely to be increasing due to increased prescription of
      selective serotonin reuptake inhibitor antidepressants and tramadol, as well as
      recreational use of amphetamine-like substances. Serotonin syndrome may
      complicate the administration of drugs frequently used in anaesthetic practice,
      including pethidine and tramadol. Although the majority of cases improve with
      symptomatic and supportive care, severe cases need intensive care and frequently
      require mechanical ventilation. Neuromuscular excitability is likely to be the
      cause of rhabdomyolysis seen in severe cases and should be treated with
      benzodiazepines and muscle relaxants. Supportive therapies are required to treat
      hyperthermia and autonomic dysfunction. Cyproheptadine is the most commonly
      administered serotonergic antagonist, but is unavailable in parenteral form.

PMID- 15960400
TI  - Antibiotic resistance in the intensive care unit: a primer in bacteriology.
AB  - The clinical use of potent, well-tolerated, broad-spectrum antibiotics has been
      paralleled by the development of resistance in bacteria, and the prevalence of
      highly resistant bacteria in some intensive care units is despairingly
      commonplace. The intensive care community faces the realistic prospect of
      untreatable nosocomial infections and should be searching for new approaches to
      diagnose and manage resistant bacteria. In this review, we discuss some of the
      relevant underlying biology, with a particular focus on genetic transfer vehicles
      and the relationship of selection pressure to their movements. It is an attempt
      to demystify the relevant language and concepts for the anaesthetist and
      intensivist, to explain some of the reasons for the emergence of resistance in
      bacteria, and to provide a contextual basis for discussion of management
      approaches such as selective decontamination and antibiotic cycling.

PMID- 15960401
TI  - Recombinant activated factor VIIa use in massive transfusion and coagulopathy
      unresponsive to conventional therapy.
AB  - We report a retrospective analysis of patients admitted to a tertiary intensive
      care unit who received recombinant activated factor VIIa (rFVIIa) in an effort to
      control life-threatening haemorrhage and coagulopathy. Data extracted included:
      demographics, diagnoses and clinical course, dosage of rFVIIa, blood product
      requirements and coagulation tests prior to and after rFVIIa, pH, base deficit
      and temperature. During the study period rFVIIa was given to nine patients with
      refractory coagulopathy in imminent danger of death. Three patients were post
      cardiac surgery, three patients had multiple blunt trauma, one patient had a
      close range shotgun wound to the abdomen, one patient had a ruptured iliac artery
      aneurysm and one patient was post caesarean section with acute fatty liver of
      pregnancy. Improvements in prothrombin time (PT) (median 17s pre vs 10.6s post
      rFVIIa (P < 0.05)) were seen in all nine cases. Reduced requirements for red
      blood cells, fresh frozen plasma, platelets and cryoprecipitate followed rFVIIa
      administration in eight cases. One patient died after 48 hours of complications
      unrelated to the initial pathology. Seven patients were discharged from hospital;
      one remains in hospital. rFVIIa provided improvement in coagulopathy unresponsive
      to conventional therapy.

PMID- 15960402
TI  - Evaluation of random plasma cortisol and the low dose corticotropin test as
      indicators of adrenal secretory capacity in critically ill patients: a
      prospective study.
AB  - It is unclear whether a random plasma cortisol measurement and the corticotropin
      (ACTH) test adequately reflect glucocorticoid secretory capacity in critical
      illness. This study aimed to determine whether these tests provide information
      representative of the 24 hour period. Plasma cortisol was measured hourly for 24
      hours in 21 critically ill septic patients followed by a corticotropin test with
      1 microg dose administered intravenously. Serum and urine were analysed for ACTH
      and free cortisol respectively. Marked hourly variability in plasma cortisol was
      evident (coefficient of variation 8-30%) with no demonstrable circadian rhythm.
      The individual mean plasma cortisol concentrations ranged from 286 +/- 59 nmol/l
      to 796 +/- 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated
      with both random plasma cortisol (r2 0.9, P < 0.0001) and the cortisol response
      to corticotropin (r2 0.72, P < 0.001). Only nine percent of patients increased
      their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response).
      However, 35% of non-responders had spontaneous hourly rises > 250 nmol/l thus
      highlighting the limitations of a single point corticotropin test. Urinary free
      cortisol was elevated (865 +/- 937 nmol) in both corticotropin responders and non
      responders suggesting elevated plasma free cortisol. No significant relationship
      was demonstrable between plasma cortisol and ACTH. We conclude that although
      random cortisol measurements and the low dose corticotropin tests reliably
      reflect the 24 hour mean cortisol in critical illness, they do not take into
      account the pulsatile nature of cortisol secretion. Consequently, there is the
      potential for erroneous conclusions about adrenal function based on a single
      measurement. We suggest that caution be exercised when drawing conclusions on the
      adequacy of adrenal function based on a single random plasma cortisol or the
      corticotropin test.

PMID- 15960403
TI  - Diagnosis and outcome from suspected mesenteric ischaemia following cardiac
      surgery.
AB  - A three-year retrospective chart review was undertaken of all post-cardiothoracic
      ICU patients who underwent laparotomy for suspected mesenteric ischaemia, or who
      had the diagnosis confirmed at post mortem. The aim was to compare the clinical
      and diagnostic characteristics of cardiothoracic patients with suspected
      mesenteric ischaemia with patients who had a confirmed diagnosis. There were 3024
      admissions to the cardiothoracic ICU over the three-year period. Twenty-six
      laparotomies were performed for suspected mesenteric ischaemia and 15 were
      positive for mesenteric ischaemia. The overall incidence of mesenteric ischaemia
      was 17/3024 (0.6%). Mortality for patients with mesenteric ischaemia was 13/17
      (76%). Ischaemia was limited to a single segment of bowel in the four survivors.
      Mortality in patients who had a negative laparotomy for suspected mesenteric
      ischaemia was 7/11 (64%), attributable to cardiovascular failure (2/11) and multi
      organ dysfunction syndrome (5/11). No clinical, biochemical or haematological
      test was discriminatory for mesenteric ischaemia. In patients with proven
      ischaemia, 7/13 plain abdominal radiographs were positive for ischaemia and 7/7
      radiographs were negative for ischaemia in patients with no ischaemia (P = 0.05,
      PPV 1.0, NPV 0.5, sensitivity 54%, specificity 100%). Neither routine clinical
      investigations nor plain abdominal radiography reliably diagnose mesenteric
      ischaemia when the diagnosis is suspected clinically. Early laparotomy is
      recommended in these patients and further investigation may delay this procedure
      unnecessarily. The presence of mesenteric ischaemia identifies a cohort of
      patients with high mortality.

PMID- 15960404
TI  - Comparison of oxygen cost of breathing between pressure-support ventilation and
      airway pressure release ventilation.
AB  - We compared the oxygen cost of breathing between pressure-support ventilation
      (PSV) and airway pressure release ventilation (APRV). This prospective,
      randomized, crossover study was conducted in a mixed ICU of a university
      hospital. Twenty clinically stable and spontaneously breathing patients after
      long-term mechanical ventilation were included. The patients were randomized to
      start on either PSV or APRV mode and measurements were obtained after an
      adaptation period of 30 minutes with a PaCO2 between 35-45 mmHg and PaO2 above 60
      mmHg. Patients were then switched to the other mode and the same measurements
      were repeated. Indirect calorimetry was performed during each ventilatory mode
      for a period of 30 minutes. Oxygen consumption, energy expenditure, CO2
      production, and respiratory quotient were measured. The parameters did not differ
      significantly between the two ventilatory modes, regardless of the patient's
      randomization. There were no statistically significant differences with regard to
      respiratory rate, minute volume, and blood gas analysis. All patients tolerated
      both ventilatory modes without signs of discomfort. PSV and APRV produced similar
      results in terms of oxygen cost of breathing and other metabolic variables.

PMID- 15960406
TI  - A novel technique for post-pyloric feeding tube placement in critically ill
      patients: a pilot study.
AB  - Delivery of enteral nutrition in critically ill patients is often hampered by
      gastric stasis necessitating direct feeding into the small intestine. Current
      techniques for placement of post-pyloric feeding catheters are complex, time
      consuming or both, and improvements in feeding tube placement techniques are
      required. The Cathlocator is a novel device that permits real time localisation
      of the end of feeding tubes via detection of a magnetic field generated by a
      small electric current in a coil incorporated in the tip of the tube. We
      performed a pilot study evaluating the feasibility of the Cathlocator system to
      guide and evaluate the placement of (1) nasoduodenal feeding tubes, and (2)
      nasogastric drainage tubes in critically ill patients with feed intolerance due
      to slow gastric emptying. A prospective study of eight critically ill patients
      was undertaken in the intensive care unit of a tertiary hospital. The Cathlocator
      was used to (1) guide the positioning of the tubes post-pylorically and (2)
      determine whether nasogastric and nasoduodenal tubes were placed correctly. Tube
      tip position was compared with data obtained by radiology. Data are expressed as
      median (range). Duodenal tube placement was successful in 7 of 8 patients
      (insertion time 12.6 min (5.3-34.4)). All nasogastric tube placements were
      successful (insertion time 3.4 min (0.6-10.0)). The Cathlocator accurately
      determined the position of both tubes without complication in all cases. The
      Cathlocator allows placement and location of an enteral feeding tube in real time
      in critically ill patients with slow gastric emptying. These findings warrant
      further studies into the application of this technique for placement of post
      pyloric feeding tubes.

PMID- 15960405
TI  - Randomized double-blind comparison of ketamine-propofol, fentanyl-propofol and
      propofol-saline on haemodynamics and laryngeal mask airway insertion conditions.
AB  - The aim of this prospective, double-blind, randomized, placebo-controlled
      clinical trial was to investigate whether the administration of ketamine before
      induction with propofol improves its associated haemodynamic profile and
      laryngeal mask airway (LMA) insertion conditions. Ninety adult patients were
      randomly allocated to receive either ketamine 0.5 mg x kg(-1) (n = 30), fentanyl
      1 microg x kg(-1) (n = 30) or normal saline (n = 30), before induction of
      anaesthesia with propofol 2.5 mg x kg(-1). Insertion of the LMA was performed 60s
      after injection of propofol. Arterial blood pressure and heart rate were measured
      before induction (baseline), immediately after induction, immediately before LMA
      insertion, immediately after LMA insertion and every minute for three minutes
      after LMA insertion. Following LMA insertion, the following six subjective
      endpoints were graded by a blinded anaesthestist using ordinal scales graded 1 to
      3: mouth opening, gagging, swallowing, movement, laryngospasm and ease of
      insertion. Systolic blood pressure was significantly higher following ketamine
      than either fentanyl (P = 0.010) or saline (P = 0.0001). The median
      (interquartile range) summed score describing the overall insertion conditions
      were similar in the ketamine [median 7.0, interquartile range (6.0-8.0)] and
      fentanyl groups [median 7.0, interquartile range (6.0-8.0)]. Both appeared
      significantly better than the saline group [median 8.0, interquartile range (6.75
      9.25); P = 0.024]. The incidence of prolonged apnoea (> 120s) was higher in the
      fentanyl group [23.1% (7/30)] compared with the ketamine [6.3% (2/30)] and saline
      groups [3.3% (1/30)]. We conclude that the addition of ketamine 0.5 mg x kg(-1)
      improves haemodynamics when compared to fentanyl 1 microg x kg(-1), with less
      prolonged apnoea, and is associated with better LMA insertion conditions than
      placebo (saline).

PMID- 15960407
TI  - Effect of nitrous oxide in reducing pain of propofol injection in adult patients.
AB  - In a randomized, double-blind, prospective trial we compared the efficacy of pre
      treatment with nitrous oxide (with or without premixed lignocaine in propofol)
      for the prevention of propofol-induced pain. Ninety consecutive patients were
      recruited in the study and divided into three groups of 30 each, who received
      either 50% nitrous oxide in oxygen along with lignocaine 40 mg mixed in 1%
      propofol 20 ml (Group NL), 50% nitrous oxide in oxygen without lignocaine in
      propofol (Group N), and 50% oxygen in air with lignocaine mixed in propofol 40 mg
      (Group L). Pain scores were graded on a four point verbal rating scale (0-3).
      Eighty-nine patients completed the study while one patient developed excitement,
      agitation and tremor during nitrous oxide in oxygen inhalation. Eleven patients
      (36.7%) complained of pain in the group L compared to 7 (23.3%), and 1 (3.3%), in
      groups N and NL respectively [group NL vs group L (P < 0.001) and group NL vs N
      (P < 0.001)]. There was no statistical difference observed between group N and
      group L. Inhalation of 50% nitrous oxide reduces pain on propofol injection. The
      combination of 50% nitrous oxide and lignocaine mixed with propofol was the most
      effective treatment.

PMID- 15960408
TI  - The ProSeal laryngeal mask airway size selection in male and female patients in
      an Asian population.
AB  - The aim of this study was to investigate if size 5 compared with size 4 ProSeal
      laryngeal mask airway (PLMA) in Asian men and size 4 compared with size 3 ProSeal
      laryngeal mask airway (PLMA) in Asian women, would give a better glottic seal. We
      conducted a randomized crossover study involving 30 male and 30 female patients
      of Asian origin. Size 4 and size 5 PLMA were studied in men and size 3 and size 4
      PLMA were studied in women. The patients were anaesthetized and paralysed and the
      PLMA was inserted with the introducer. The oropharyngeal leak pressure (OLP),
      ease of insertion, anatomical position, mucosal injury, visibility of cuff in the
      mouth and volume of air required to achieve an intracuff pressure of 60 cmH2O
      were studied. In male patients, oropharyngeal leak pressure was higher when size
      5 PLMA was used (P < 0.001) and there was a higher incidence of mucosal injury (P
      = 0.025). For female patients, oropharyngeal leak pressure was higher with size 4
      PLMA (P = 0.036) while the number of insertion attempts, anatomical position and
      mucosal injury were similar. The cuff was not visible in the oral cavity in any
      cases. The mean volume of air required to achieve an intracuff pressure of 60
      cmH2O was less than the maximum recommended by the manufacturers. The size 5 PLMA
      in Asian men and size 4 PLMA in Asian women resulted in a more effective glottic
      seal. The use of size 5 PLMA in Asian men led to increased mucosal injury.

PMID- 15960409
TI  - A comparison of the GlideScope with the Macintosh laryngoscope for tracheal
      intubation in patients with simulated difficult airway.
AB  - We compared the use of the GlideScope and the conventional Macintosh laryngoscope
      in a simulated difficult airway. The primary hypothesis was that time to
      intubation would be shorter using the GlideScope than using the Macintosh
      laryngoscope. After obtaining approval from the ethics committee and written
      informed consent, we recruited 60 ASA 1 and 2 patients to our randomized
      controlled trial. Group G (n = 30) had tracheal intubation performed using the
      GlideScope and Group M (n = 30) were intubated using a Macintosh laryngoscope. We
      simulated a difficult airway in each patient by having an experienced assistant
      provide in-line manual stabilization of the head and neck. We recorded the best
      laryngeal view; difficulty of the tracheal intubation; time taken for successful
      tracheal intubation; manoeuvre needed to aid tracheal intubation and
      complications associated with the tracheal intubation. The median Cormack and
      Lehane grade was significantly better in Group G than Group M. Group G had a
      significantly shorter intubation time than group M (mean 41.8s +/- SD 20.2 vs
      mean 56.2s +/- 26.6, P < 0.05). The GlideScope improved the laryngeal view and
      decreased time for tracheal intubation time when compared with the Macintosh
      laryngoscope in patients with simulated difficult airway. The GlideScope may be a
      good alternative for managing the difficult airway but clinical trials evaluating
      its use on patients with an actual difficult airway are needed.

PMID- 15960411
TI  - Personal digital assistant (PDA) use amongst anaesthetists: an Australian survey.
AB  - We report an email questionnaire survey of Personal Digital Assistants (PDA) use
      amongst members of the Australian Society of Anaesthetists (ASA). PDAs are
      becoming increasingly popular and they have many applications within the
      healthcare community. Seventy-eight per cent of members of the ASA have an email
      address (1870/2385) although only 38% (900/2385) of members are regular uses of
      email. We surveyed 1870 members of the ASA and received 215 responses (11%
      response rate). We found that 91% of anaesthetists answering the survey used a
      PDA and of these 72% use a Palm operating system, which reflects current market
      trends. Anaesthetists use PDAs for a wide range of facilities: appointments, drug
      reference, contact details and "tasks to do" being the most utilized. The most
      common software programs added to the operating system were pharmacopoeias,
      contact managers and database programs.

PMID- 15960410
TI  - Substance abuse by anaesthetists in Australia and New Zealand.
AB  - A questionnaire investigating substance abuse was sent to 128 anaesthetic
      departments in Australia and New Zealand of which 100 (78%) replied. Forty-four
      cases of substance abuse were reported. Abusers were more likely to be male, aged
      between 25 and 35 years and abusing opioids. Death was the eventual outcome in
      24% of cases. Only 19% of abusers made a long-term recovery within the specialty.
      Initial signs of abuse were most commonly abnormal conduct (63% of the cases) and
      observed abuse (37%). More than one precipitating cause was identified in 51% of
      cases, the most frequently reported were mental health and family problems. The
      pattern of substances abused was similar to that reported in the previous
      Australasian survey ten years ago. However, in keeping with an international
      trend, there appears to be an increased use of anaesthetic agents.

PMID- 15960412
TI  - A teenager with severe asthma exacerbation following ibuprofen.
AB  - Aspirin-sensitive asthma, aspirin-intolerant asthma, aspirin- (or non-steroidal
      anti-inflammatory drug [NSAID]) exacerbated respiratory disease are terms for a
      disorder commonly described as affecting adults aged > 30y. With this perception,
      ibuprofen was administered for postoperative pain management to a 17-year-old boy
      with allergic rhinitis and previous severe asthma (at a time when well
      controlled), who then had a severe asthma exacerbation. Analysis of the
      literature in response to this case highlights four points: 1) NSAID-exacerbated
      asthma is not only a disorder of adults; it occurs in up to of 2% in asthmatic
      children, approaching probably 30% in older children with severe asthma and nasal
      disease. 2) The asthmatic reaction is dose-dependent and can occur with sub
      therapeutic doses. Oral NSAID/aspirin challenge should be conducted in an
      environment where a severe asthma exacerbation can be appropriately managed. 3)
      The therapeutic use of non-selective [COX-1 preferential] NSAIDs should be
      avoided when sensitivity is known or suspected in adults and teenagers with
      severe asthma and chronic rhinosinusitis or nasal polyps. Use of these agents in
      younger children with mild episodic wheeze is probably safe. 4) Paracetamol use
      is probably safe, but aspirin-exacerbated respiratory disease may occur with
      clinical doses in a subgroup of aspirin-exacerbated respiratory disease patients.
      COX-2 selective inhibitors are probably safe, although this is controversial.
      Opioids and tramadol are suitable analgesic alternatives for patients with known
      or suspected susceptibility.

PMID- 15960413
TI  - Brugada syndrome following tricyclic antidepressant overdose.
AB  - The Brugada syndrome, a pro-arrhythmogenic repolarization abnormality, is
      becoming increasingly recognised as a cause of collapse and sudden cardiac death.
      We report a case of a 48-year-old man with a tricyclic overdose and a delayed
      presentation of the Brugada pattern in the ICU. This case raises the need for
      clinicians to be aware of the Brugada pattern and those patients potentially at
      risk.

PMID- 15960414
TI  - An unusual complication of thrombolysis--bilateral retro-orbital haematomata.
AB  - We present a case of bilateral retro-orbital haematomata following thrombolysis
      of pulmonary embolism in a severely haemodynamically compromised 29-year-old
      female. The haematomata developed two days post-thrombolysis with marked visual
      impairment. Visual acuity was restored following bilateral drainage of the
      superior aspects of the retro-orbital space.

PMID- 15960415
TI  - High-frequency jet ventilation through a fibreoptic bronchoscope channel during
      lung lavage.
AB  - Simple manual ventilation facilitates removal of intra-alveolar accumulations.
      High-frequency jet ventilation can be performed through a narrow lumen like that
      of a fibreoptic bronchoscope. Accordingly, we expected that high frequency jet
      ventilation through a fibreoptic bronchoscope channel would facilitate lung
      lavage, and we developed a new bronchoalveolar lavage system, in which high
      frequency jet ventilation through the channel of a fibreoptic bronchoscope was
      combined with conventional bronchoalveolar lavage. We describe a case in which
      this new lavage system, unlike conventional bronchoalveolar lavage, successfully
      removed the lipid material in the alveoli associated with pulmonary alveolar
      proteinosis.

PMID- 15960416
TI  - A method to facilitate nasoenteral feeding tube placement.

PMID- 15960417
TI  - Thomo bag.

PMID- 15960418
TI  - Laryngospasm induced by topical application of lignocaine.

PMID- 15960419
TI  - [The "evil" pharmacists].

PMID- 15960420
TI  - [Chickenpox (Varicella) and shingles (Herpes zoster)].

PMID- 15960422
TI  - [Color changes in the urine].

PMID- 15960421
TI  - [Treatment of diabetes mellitus. New developments and hopes].

PMID- 15960423
TI  - Synthesis and evaluation of N-(5-methyl-3-oxo-1,2- diphenyl-2,3-dihydro-1H
      pyrazol-4-yl)-N'-phenylureas as cholecystokinin antagonists.
AB  - In the search for new cholecystokinin (CCK) ligands, ureidopyrazolines were
      identified in combinatorial libraries using 168 chemically diverse amines. The
      structure-activity relationship optimisation of this pyrazoline template 4a
      resulted in novel 3-oxo-1,2-diphenyl-2,3-di-hydro-1H-pyrazol-4-yl)-N'-phenylureas
      5a-5o. These novel CCK ligands have shown to act as mixed CCK-A/CCK-B ligands in
      a [125]I-CCK-8 receptor binding assay. The best pyrazoline 5e of this series
      displayed an IC50 of 20 and 25 nmol/L for the CCK-A, and CCK-B receptor,
      respectively. In a subsequent in vivo evaluation using various behavior
      pharmacological assays, an anxiolytic effect of these novel diphenylpyrazolinyl
      ureas was found in the elevated x-maze with an ED50 of 1.7 mg/kg. In the despair
      swimming test, a model for testing antidepressants, an ED50 of 0.69 mg/kg was
      determinated for urea 5e and the antidepressant effect had a magnitude comparable
      to desimipramine.

PMID- 15960424
TI  - Synthesis and anticonvulsant activity of some new hexahydropyrimidine-2,4-dione
      derivatives.
AB  - In this study, twelve new hexahydropyrimidine-2,4-dione derivatives were
      synthesized and screened for their anticonvulsant activities. All the compounds
      (7a-1) which have 6-arylhexahydropyrimidine-2,4-dione and N,N-disubstituted
      dithiocarbamate structures were prepared by the reaction with appropriate 3-(2
      chloroethyl)-6-arylhexahydropyrimidine-2,4diones and the corresponding N,N
      disubstituted dithiocarbamate potassium salts. The structure of the synthesized
      compounds was confirmed by UV, IR, 1H-NMR and elemental analysis. Their
      anticonvulsant activities were determined by maximal electroshock (MES),
      subcutaneous pentetrazol (metrazol, scMet) and rotorod toxicity tests for
      neurological deficits. According to the activity studies, 6-(4
      chlorophenyl)hexahydropyrimidine-2,4-dione derivatives (7e-h) were found to be
      highly protective against MES and scMet. Neurotoxicity was not observed in any of
      the tested compounds.

PMID- 15960425
TI  - Structure-activity relationship study of some triazolinone based compounds with
      antagonistic balanced activity on angiotensin II receptor subtypes AT1 and AT2. A
      three-dimensional quantitative structure-activity relationship investigation.
AB  - Angiotensin II (AII) receptor antagonists have attracted much attention as anti
      hypertensive agents in recent times following the discovery of side effects
      associated with angiotensin converting enzyme (ACE) inhibitors. Various lead
      structures of the compounds of this category are reported in the literature.
      Studying the structure-activity relationships (SAR) for such compounds has been a
      fascination for scientists and efforts have been made to identify the essential
      physico-chemical requirements for the angiotensin type 1 (AT1) receptor
      selective, angiotensin type 2 (AT2) receptor selective and some AT,/ AT2 balanced
      antagonistic activity compounds. With an aim to identify the structural
      requirements for balanced activity and differentiate between the features
      individually responsible for AT1 and AT2 antagonistic activities, a quantitative
      SAR (QSAR) analysis was carried out on a series of triazolinone based balanced
      AII receptor antagonists. The statistically significant equations with r > 0.88,
      chance < 0.01, q2 > 0.60 and F values at least three times greater than those
      reported were obtained for both AT1 and AT2 receptor subtypes antagonistic
      activities. A comparative study of the parameters responsible for AT1 and AT2
      receptor antagonistic activities is carried out in order to identify the features
      that can be modulated to obtain balanced compounds. It has been observed that the
      most reliable equations obtained in the study show the contribution of
      hydrophobic parameters: logarithm of partition coefficient (logP), thermodynamic
      parameters: bend energy (Eb), and electronic parameters: electronic energy
      (Eelec) parameters towards AT1 anatgonistic activity, and thermodynamic
      parameters: total energy (E), steric parameters: principal moment of inertia
      along the Y-axis (PMIY) and electronic parameters: electronic energy (Eelec)
      parameters towards AT2 antagonistic activity. The parameter Eelec is common but
      its effect towards the two activities is opposite, negative for AT1 and positive
      for AT2.

PMID- 15960428
TI  - Structure-activity relationship studies of new acronine analogues as suggested by
      molecular descriptors.
AB  - This work describes the results of an investigation on the structure-activity
      relationships of a series of acronine (CAS 7008-42-6) analogues which possess
      cytotoxic and antitumor activity. The results were obtained employing a
      commercially available software, which correlates structure and activity through
      calculations with different descriptors. The best results, obtained with
      electrostatic descriptors, led to propose new structures which present higher
      calculated activity than that of acronine.

PMID- 15960426
TI  - Clinical study on the effect of simvastatin on butyrylcholinesterase activity.
AB  - Although the physiological function of serum butyrylcholinesterase (BuChE) has
      not yet been clarified, there is evidence that this enzyme is involved in serum
      lipoprotein metabolism. It has been suggested that serum BuChE is positively
      correlated with LDL (low-density lipoprotein) and negatively with HDL (high
      density lipoprotein) levels. The objective of this study was to determine whether
      the activity of BuChE changes during treatment with simvastatin (CAS 79902-63-9).
      The effects of simvastatin therapy on serum lipoproteins and plasma BuChE
      activity were studied in 15 patients with type IIa and 17 patients with type IIb
      hyperlipoproteinemia. Beside the expected influence on serum lipid concentration,
      a statistically significant decrease in BuChE activity in patients with
      hyperlipoproteinemia type IIa and IIb during treatment with simvastatin was not
      observed.

PMID- 15960429
TI  - Concentration-effect relationships of alcohol in a computerised psychometric test
      system.
AB  - The purpose of this study was to validate a computerised psychometric test system
      by demonstrating the change of the test variables of the Bochum Diagnostic System
      after administration of alcohol. Twenty-four healthy young male or female
      volunteers participated in a doubleblind, randomised, placebo-controlled study in
      a 3-way cross-over design. The volunteers took single doses of placebo, 0.4 and
      0.7 g alcohol/kg body weight (females: 10% less) in a random sequence.
      Psychometric tests were performed before as well as 1 and 3 h after the
      administration of alcohol. The effects of alcohol on the psychometric performance
      were most pronounced 1 h after administration. At this time a significant dose
      dependent impairment of performance in the concentration test, the simple and
      complex reaction tests, the vigilance test and the coordination test was
      observed. 3 h after administration, significant effects were only observed in the
      complex reaction test and the concentration test. Maximal alcohol serum
      concentrations of 0.47 +/- 0.05 % per thousand and of 0.90 +/- 0.15 % per
      thousand were reached after administration of 0.4 g/kg and 0.7 g/kg,
      respectively. The correlations between individual serum alcohol concentrations
      and differences of psychometric variables from baseline were significant. It is
      concluded that the tests of the Bochum Diagnostic System can quantitatively
      measure the effects of alcohol. The most sensitive tests are the complex reaction
      test and the concentration test.

PMID- 15960427
TI  - Open comparative, randomized controlled clinical study of a new immunostimulating
      bacterial lysate in the prophylaxis of upper respiratory tract infections.
AB  - One hundred and fourteen patients with a medical history of recurrent upper
      respiratory tract infections (at least four episodes in the year preceding this
      open comparative study) were randomly assigned to three groups of 38 patients
      each. The first group received, by sublingual route, Ismigen, a new
      immunostimulating lysate (Polivalent Mechanical Bacterial Lysate, PMBL) obtained
      by mechanical lysis of 48 billion bacteria commonly responsible for upper
      respiratory tract infections; the second group received an oral immunostimulating
      lysate (CLBL) obtained by chemical lysis of 36 billion bacteria. A third group
      served as control and did not receive any immunostimulating treatment (Control
      NT). One tablet a day of PMBL was given to the first group for the first ten days
      during three consecutive months; the patients of the second group received one
      capsule a day of CLBL with the same treatment schedule. At the end of the
      treatment period the patients of the 3 groups were followed up for 3 months. The
      primary end point was the number of acute upper respiratory tract infections
      (URTIs) that occurred during the three months of treatment and three months of
      follow-up. Secondary endpoints were: the number of patients free from disease,
      the duration of infectious episodes, the number of working days lost because of
      disease, the need for a concomitant antibiotic treatment, and the safety of the
      two treatments. During the treatment period the mean number (+/- SD) of URTIs per
      patient was 0.34 (0.48) in the PMBL group, 1.0 (0.83) and 1.23 (0.77) in the CLBL
      and Control NT groups, respectively. Results of PMBL treatment were significantly
      better (p < 0.05) than the results in the other two groups; CLBL was not
      significantly different from the control group. In the three months of follow-up,
      the mean number (+/- SD) of URTIs per patient was: 0.42 (0.55) in the PMBL group,
      0.92 (0.67) in the CLBL group, and 1.55 (0.88) in the Control NT group. The PMBL
      group was significantly better than the other two (p < 0.05). During the 6-month
      study, significantly more patients of the PMBL group remained free from
      respiratory infections in comparison to the other two groups. As regards other
      secondary end points (duration of infectious episodes and number of working days
      lost), the mean values of the PMBL group were statistically significantly lower
      than those of the other two groups, in both the treatment and follow-up periods.
      No PMBL treated patient needed concomitant administration of an antibiotic, while
      9 patients of the CLBL group received such treatment (p < 0.05). No patient
      reported adverse events.

PMID- 15960430
TI  - [Learning and memory amelioration of transplantation of the neural stem cells
      modified with human brain-derived neurotrophic factor gene on Alzheimer disease
      model rat].
AB  - OBJECTIVE: To investigate the memory amelioration of the Alzheimer disease (AD)
      model rat after being transplanted the single neural stem cells (NSC) and NSC
      modified with human brain-derived neurotrophic factor (hBDNF) gene. METHODS:
      Forty SD rats were divided evenly into 4 groups randomly. The AD model rats were
      made by cutting unilaterally the fibria-fornix of male rats. Ten to twelve days
      after surgery, the genetically modified and unmodified NSC were implanted into
      the lateral cerebral ventricle of group III and group IV respectively. Two weeks
      after transplantation, the amelioration of memory impairment of the rats was
      detected by Morris water maze. RESULTS: The average escaping latency of the group
      III and group IV (41.84 +/- 21.76 s, 25.23 +/- 17.06 s respectively) was shorter
      than that of the group II (70.91 +/- 23.67 s) (P<0.01). The percentage of
      swimming distance in the platform quadrant in group III (36.9%) and in group IV
      (42.0%) was higher than that in the group II (26.0%) (P<0.01). More marginal and
      random strategies were used in group II. The percentage of swimming distance in
      the platform quadrant in group IV was also greater than that in group III
      (P<0.05). There were no significant differences in the average escaping latency,
      the percentage of swimming distance in the platform quadrant and the probe
      strategy between group IV and group I (P>0.05). More lineal and oriented
      strategies were used in group IV. CONCLUSION: The behavioral amelioration of AD
      model rat was obtained by transplanting single NSC and hBDNF-gene-modified NSC.
      The effect of the NSC group modified with hBDNF gene is better than that of the
      group III.

PMID- 15960431
TI  - [Resection of extensive pituitary adenoma via supraorbital keyhole with endoscope
      assisted microneurosurgery].
AB  - OBJECTIVE: To study the methods and techniques of the treatment for extensive
      suprasellar pituitary adenoma and repairing hole. METHODS: From Feb. 2001 to Mar.
      2003, 9 patients with extensive suprasellar pituitary adenoma underwent resection
      via supraorbital keyhole with endoscope-assisted microneurosurgery. Then the
      remaining tumor was removed with neuro-endoscopy via I and II space of optic
      chiasma. The small bone flap was fixed with Ti clamp. RESULTS: After the tumor
      was removed with microneurosurgery, the remaining tumor was still found with
      endoscope in 7 cases. Remaining tumor was totally removed in 6 cases, almost
      removed in 3 cases. The vision improvement was found in 7 cases one week after
      surgery. In the other 2 cases, the vision remained unchanged. Follow-up was
      conducted in 6 cases for 6 to 22 months. Neuroradiological recovery of MRI with
      no recurrence of tumor was observed. No complication of incision was present.
      CONCLUSION: Enough intra and extra-cranial space can be provided to operate via
      orbital roof approach to sellar tumors. Endoscope-assisted microneurosurgery can
      increase the total-resection and successful rate treatment for extensive
      suprasellar pituitary adenoma, reduce the possibility of complication, and
      protect the function of brain from being injured. Fixation of small bone flap
      with Ti clamp is safe, easy and reliable.

PMID- 15960432
TI  - [Reconstruction of chest wall after resection].
AB  - OBJECTIVE: To evaluate the results of chest wall reconstruction (CWR) in patients
      who underwent chest wall tumor resection accompanying huge chest wall defect.
      METHODS: From Jan. 1998 to Mar. 2003, 31 patients underwent CWR. Among them, 20
      were male and 11 female. The age ranged from 8 to 72 years. The indications for
      resection were primary chest wall tumor in 21 patients, lung cancer with invasion
      of chest wall 6, recurrence of breast cancer 2, radiation necrosis 1 and skin
      cancer 1. The number of rib resected was 2-7 ribs (3.6 in average). The defect
      was 20-220 cm2 (97.1 cm2 in average). Concomitant resection was done in 13
      patients, including lobectomy or wedge resection of lung 10, partial resection of
      diaphragm 2, and partial sternotomy 1. Seven patients underwent soft tissue
      reconstruction alone (latissimus dorsi+greater omentum, latissimus dorsi
      myocutaneous flap, latissimus dorsi muscle flap), 5 patients bony reconstruction
      alone (Prolene web), and simultaneous BR and STR were performed in 19 patients
      (latissimus dorsi, pectoralis major, latissimus dorsi+fascia lata, and Prolene
      web). RESULTS: Three patients (9.7%) developed postoperative complications.
      Postoperative survival period was 6-57 months with a median of 22 months.
      CONCLUSION: A favorable clinical outcome can be achieved by CWR for the patients
      with huge chest wall defects that result from resection of chest wall tumors.

PMID- 15960433
TI  - [Effect of basic fibroblast growth factor on wound healing of bilioenteric
      anastomosis].
AB  - OBJECTIVE: To observe the effects of basic fibroblast growth factor (bFGF) on
      wound healing of bilioenteric anastomosis as to prevent postoperative biliary
      strictures. METHODS: A model of choledochoduodenostomy in 31 dogs were
      constructed at first, then bFGF was administered on the local anastomosis (bFGF
      group) for 1 week after the operation as compared with sodium chloride solution
      (control group). Both groups were observed with light microscope (HE, Masson
      staining) and electron microscope 3 days, 1 and 3 weeks and 3 and 6 months after
      the operation (n=3). Hydroxyproline was measured at the same time. RESULTS: bFGF
      group healed more quickly compared with control group. Good function of cells
      were detected by electron microscope. Better mucosa epithelia, fibroblast, and
      capillary vessel proliferation were detected by histological observation in bFGF
      group. In bFGF group, collagen fibers were arranged orderly. Three weeks after
      operation, collagen fibers in control group were orderless and in whirlpool.
      Hydroxyproline of bFGF group was lower than that of control group (P<0.05).
      CONCLUSION: bFGF administered in local anastomosis is an effective method to
      prevent postoperative anastomotic stenosis.

PMID- 15960434
TI  - [Treatment of upper limb lymphedema after radical mastectomy with liposuction
      technique and pressure therapy].
AB  - OBJECTIVE: To study a new method of treatment for upper limb lymphedema after
      radical mastectomy. METHODS: From Jun. 2001 to Sep. 2003, 11 cases (2 with
      complication of erysipelas) of upper limb lymphedema being treated with radical
      mastectomy for more than 2 years were used as model. All the edema of limbs was
      sucked from hypodermis with liposuction technique and compressed with compression
      garment. Three months after operation, elasticity stress was conducted every
      night. RESULTS: The reduction of the edema of upper limbs was remarkable. The
      average decrease of circumference was 4 cm. No erysipelas was observed.
      CONCLUSION: The liposuction technique and elasticity stress is a new and
      effective approach to the treatment of upper limb lymphedema.

PMID- 15960435
TI  - [Treatment on femoral fractures with inverse limited marrow cavity rasping
      intramedullary interlocking nail].
AB  - OBJECTIVE: To evaluate the results of the treatment on femoral fractures with
      inverse limited marrow cavity rasping intramedullary interlocking nail. METHODS:
      From Jun. 1999 to Sep. 2003, 74 patients with femoral fractures were treated by
      intramedullary interlocking nail (inverse limited marrow cavity rasping). There
      were 62 males and 12 females. Among them, 5 cases were type 32A1, 7 cases were
      type 32A2, 12 cases were type 32A3, 35 cases were type 32B2, and 15 cases were
      type 32C2. RESULTS: Seventy-four patients were followed up for 13 to 29 months
      (15.4 months in average). The time for fracture union ranged from 3 to 5 months
      (3.8 months in average). The overall rate of excellence was 98.7% by Wuyuesong
      grading. There was 1 case of non-union, 1 case of delayed infection, and 2 cases
      of bent screw. CONCLUSION: The treatment on femoral fractures with inverse
      limited marrow cavity rasping intramedullary interlocking nail is easy to operate
      and has minimum impairment to local circulation. It also promotes the healing and
      early function.

PMID- 15960436
TI  - [Experimental study of repairing bone defect by staphylococcus aureus injection
      carried in collagen membrane].
AB  - OBJECTIVE: To validate the advantage of repairing bone defect by staphylococcus
      aureus injection carried in collagen membrane. METHODS: Twenty-four adult New
      Zealand rabbits were divided into two groups randomly. After the experimental
      model of standard bone defect had been made by operation, collagen
      membrane/staphylococcus aureus injection and staphylococcus aureus injection with
      the same quantity were transplanted in bone defect areas of the two groups
      respectively. The reconstructed tissues were observed by general method, X-ray,
      histology, and immunohistochemistry at 2nd, 4th, 6th, 8th week respectively.
      RESULTS: The experimental group showed that new bone proliferated distinctly in
      bone defect area and the proliferation lasted long, and no excessive connective
      tissue in defect area. X-ray observation showed that there was continual callus
      growth in transplantation area in early stage and the distribution of new bones
      was even in the group. Histological observation showed that there were many new
      bone growth centers in bone defect area, trabecular bones were sequentially
      distributed, and mature bone replacement was complete. Immunohistochemical
      examination showed that bone morphogenetic protein (BMP) could be seen for a long
      time and BMP took up a large part in the new bone tissues. CONCLUSION: Collagen
      membrane could prevent parenchyma from penetrating into bone defect area and
      provide room for new bone growth. As the carrier of staphylococcus, collagen
      membrane could reduce the overflow of staphylococcus and improve its curative
      effect as well.

PMID- 15960437
TI  - [Operation on upper cervical instability without injury].
AB  - OBJECTIVE: To study operative methods of treating upper cervical spine
      instability without injury. METHODS: Twenty-three cases were treated by internal
      fixation with autologous bone grafts. Atlantoaxial arthrodesis were performed in
      10 cases with interlaminar clamp (5 cases), Atlas cable system (3 cases) and
      Brooks (2 cases). Occipitocervical fusion were performed in the other 13 cases by
      using of CD-cervical (3 cases), Cervifix (8 cases) and U-stick fixation (2
      cases). RESULTS: All the 23 cases were followed up for 2. 5 years in average
      (ranged from 6 months to 5 years). Solid arthrodesis was obtained in all 23
      cases. Six months after operation, of the 20 cases with pre-operation nervous
      lesion, improvement was achieved in 16 cases. According to JOA standard and
      Hirabashi formula, the rate of improvement was 27.1%. CONCLUSION: Posterior
      fusion is recommended for upper cervical instability.

PMID- 15960438
TI  - [3-D finite element and clinical analyses of the reconstruction of the first to
      third metatarsus defect with ilium].
AB  - OBJECTIVE: To investigate the effect of first to third metatarsus defect and the
      effect of reconstruction with ilium on foot function. METHODS: The first to third
      metatarsus defect was simulated in a 3D foot model and rebuilt by ilium. The
      maximal displacement and stress calculated by the method of finite elements were
      used as the index of estimation. Five cases treated from Mar. 1996 to Jan. 2003
      with metatarsus defect rebuilding by free vascular iliac bone incorporating free
      flap were evaluated. RESULTS: Foot function was affected largely by the defect of
      the first to third metatarsus. Compared with the normal foot, the maximal
      displacement was increased by 2.15 times and the maximal stress was increased by
      2.12 times in 100%-defected foot, and in 50%-defected foot maximal displacement
      and stress were increased by 1.65 times and 2.05 times respectively. Follow-up
      had been conducted for 1 to 2 years. All bones and flaps of the 5 cases survived
      (2 excellent, 2 good, and 1 passable) by function evaluation. CONCLUSION: The
      first to third metatarsus defect should be repaired, and the method of
      transplanting iliac bone added by flap is effective.

PMID- 15960439
TI  - [A probe to the treatment of Madelung deformity].
AB  - OBJECTIVE: To explore a method of treating Madelung deformity. METHODS: Seven
      cases of Madelung deformity had been treated with the excision of ulnar carpi
      ulnaris segment and distal osteotomy of radius and tight constrict of extensor
      carpi ulnaris from Mar. 2000 to Nov. 2003. The angle of ulnar tilting was 37-70
      degrees and the angle of volar tilting was over 16 degrees. A longitudinal
      incision on each side of the radius and ulnar was made, the ulna was excised
      about 2-3 cm segment. Then the fracture of ulna was fixed by double across
      vertical steel wire and the radius was fixed with medullary wire. Lastly the
      extensor carpi ulnaris was shortened and sutured after the wrist was located rest
      position. RESULTS: After surgery, the deformity of wrist was improved and pain
      free in the seven cases. The angle of ulnar tilting was reduced to 22-24 degrees.
      The angle of volar tilting was reduced to 15 degrees below. Follow-ups were
      conducted in the 7 patients for 2 years in average. The activity of wrist joint
      and the rotation of forearm recovered from those before operation. The wrist
      joint could stretch fully. CONCLUSION: This method of treating Madelung proves to
      be effective in recovering deformity, releasing pain, improving function, and
      reducing traumatic osteoarthritics of the distal radioulnar joint.

PMID- 15960440
TI  - [Experimental study on constructing muscle tissue in rabbits with tissue
      engineering methods].
AB  - OBJECTIVE: To explore the possibility of constructing tissue engineering muscles
      by combining allogeneic myoblasts with small intestinal submucosa (SIS) in
      rabbits. METHODS: A large number of purified myoblasts were obtained with multi
      procedure digestion and repeated attachment method from skeletal muscles taken
      from extremities of immature rabbits which were born 7 days ago. The myoblasts
      were labeled with BrdU, and then combined with SIS to construct tissue
      engineering muscles. This kind of tissue engineering muscles were grafted into
      the gastrocnemius muscle defect (1.5 cm in length, 1.0 cm in width) of fifteen
      rabbits as the experimental group. The SIS was grafted into the same position in
      the control group. The rabbits were sacrificed 4, 6, 8 weeks after operation. The
      tissue engineering muscles were evaluated by macroscopic, histological and
      immunohistochemical observations, and by quantitative analysis of local
      immunocyte in the grafting site. RESULTS: Allogeneic myoblasts with SIS were
      combined perfectly in vitro. The SIS was connected tightly to surrounding
      skeletal muscles and inflammation response was obvious 4 weeks after grafting.
      The SIS began to break down and inflammation response became slight 6 and 8 weeks
      after operation. Compared with that of 8th week, the quantitative analysis of
      local immunocyte in 4th and 6th week in both experimental and control group has
      significance (P<0.05). Newly formed muscle tissues were found around SIS in the
      experimental group in 4th, 6th, and 8th week. Expression of BrdU and myosin
      immunohistochemical staining were positive in the experimental group and negative
      in the control group. CONCLUSION: Tissue engineering muscles of rabbits which are
      constructed by combining allogeneic myoblasts with SIS can survive and
      proliferate.

PMID- 15960441
TI  - [Experimental study of bone infection on WO-1 controlled-release system].
AB  - OBJECTIVE: To develop a new tissue engineering bone material which has an anti
      infective function. METHODS: Collagen loaded bio-derived bone material was made
      by using type-I collagen and allograft bone. WO-1 was absorbed to collagen loaded
      bio-derived bone, then the morphological feature of the new bone material was
      observed by scanning electronic microscopy. 3H-tetracycline was diluted by WO-1
      solution, and was absorbed to collagen loaded bio-derived bone, then the
      releasing kinetics of WO-1 was detected by 3H-tetracycline in vitro. WO-1 bio
      derived bone material was grafted into a culture medium with staphylococcus
      aureus, Escherichia coli, and pseudomonas aeruginosa to observe its
      bacteriostasis ability. WO-1 bio-derived bone material was grafted into radius of
      defected rabbits, the concentration of WO-1 was detected on the 9th, 16th, 23th,
      and 30th day by HLPC in blood, in bone and in muscle. The bacteriostasis ability
      of WO-1 loaded bio-derived bone was tested in vitro and in vivo. RESULTS: WO-1
      loaded bio-derived bone maintained natural network pore system and the surface of
      network pore system was coated with collagen membrane. The release of WO-1 from
      WO-1 loaded bio-derived bone showed bursting release on the 1st day, then showed
      stable release. WO-1 loaded bio-derived bone showed lasting and stable
      bacteriostasis to common pathogens of orthopaedic infections. The high
      concentration of WO-1 was observed in bone tissue and in muscle tissue at
      different time points and the difference among groups had no significance
      (P>0.05), while the concentration of WO-1 in blood was very low (P<0.05).
      CONCLUSION: WO-1 loaded bio-derived bone has good capability of drug controlled
      release and bacteriostasis.

PMID- 15960442
TI  - [Study on the differentiation of marrow stromal stem cells into neural cells in
      vitro].
AB  - OBJECTIVE: To investigate the neural markers' expression in the differentiation
      of marrow stromal stem cells (MSCs) into neural cells. METHODS: Rats MSCs were
      expanded as undifferentiated cells in vitro for 5 to 7 generations and cultured
      in a modified neuronal medium (MNM) after 24 hours of all-trans retinoid acid
      (ATRA) pretreatment. Immunocytochemistry was used to detect the expression of
      nestin, neuron-specific nuclear protein (NeuN), microtubule-associated protein 2
      (MAP-2) and glial fibrillary acidic protein (GFAP) at different time points.
      RESULTS: After ATRA and MNM treatment, MSCs progressively assumed neuronal
      morphological characteristics. Nestin occurred first after 24 hours of ATRA
      treatment; then NeuN expressed after 2 hours of MNM treatment; the last one was
      MAP-2 and it was detected after 9 hours of MNM treatment. Other markers
      continuously expressed except that the expression of nestin peaked after 18 hours
      of MNM induction and remarkably decreased after 36 hours. CONCLUSION: ATRA and
      MNM could promote the differentiation of MSCs into neural cells and the
      expression of neural-specific markers was consistent with current knowledge
      regarding the time points of markers expression in the neuronal development which
      provides a good model in vitro for neuronal development research.

PMID- 15960443
TI  - [Construction of eukaryotic expression vector for human angiopoietin 1 and its
      expression in the marrow mesenchymal stem cells of rabbit].
AB  - OBJECTIVE: To investigate the possibility of constructing eukaryotic expression
      vector for human angiopoietin 1 (hAng-1), transfecting it to bone marrow
      mesenchymal stem cells (MSCs) so as to repair bone defect. METHODS: The
      eukaryotic expression vector pcDNA3-hAng-1 was constructed by recombinant DNA
      technique, transfected into MSCs by liposome DOTAP, and selected with G418. The
      hAng-1 expression of mRNA and protein was detected by reverse transcript-PCR and
      Western Blot. RESULTS: After the recombinant eukaryotic expression vector for
      hAng-1 was digested with Xho-I and BamH-I, electrophoresis revealed 1.4 kb
      fragment for hAng-1 gene and 5.4 kb fragment for pcDNA3 vector. In the
      transfected MSCs, the mRNA and protein expression of hAng-1 gene were detected
      with reverse transcript-PCR and Western Blot. CONCLUSION: The constructed
      eukaryotic expression vector hAng-1 could be expressed in the transfected MSCs,
      thus to provide the basis for bone repair with tissue engineering.

PMID- 15960444
TI  - [Experimental study of immunological tolerance induced by cytotoxic T lymphocyte
      associated antigen 4 immunoglobulin in fresh bone allografts].
AB  - OBJECTIVE: To study the immunological tolerance induced by blocking the second
      signal of T cell with extrinsic cytotoxic T lymphocyte-associated antigen 4
      immuno globulin (CTLA4-Ig). METHODS: Fifty-four BALB/C mice, inbred strains, were
      employed as recipients of bone allografts, using a model of heterotopic muscle
      pouch. The 54 mice were divided into 3 groups and 18 for each group. The first
      group, in which the donor was C57BL/6 with intraperitoneal injection of L6 (as a
      control), was named AL group. The second group, also C57BL/6 with injection CTLA4
      Ig, was named AC group. The third group, homologous BALB/C with injection of PBS
      buffer solution, was named AB group. The serum antibody, lymphocyte proliferation
      of the second stimulation by splenic cell and bone supernatant of donor, the
      analysis of lymphocyte subsets, a regraft experiment and histology were
      determined 2, 4 and 6 weeks after transplantation. The second transplantation was
      to regraft C57BL/6 (BC group) and C3H (BH group) mice respectively after first 12
      mice being transplanted with C57BL/6 and injected with CTLA4-Ig as to detect
      donor-specificity of immunological tolerance. RESULTS: Compared with AB group, AL
      group created more intensive immune rejection: CD4 T cell subsets (P<0.05), the
      serum antibody (P<0.05) and lymphocyte proliferation of the second stimulation by
      splenic cell and bone supernatant of donor (P<0.01 and 0.05) were significantly
      increased. However, the results of AC group showed that CTLA4-Ig significantly
      inhibited the immune rejection: CD4 T cell subsets (P>0.05), the serum antibody
      (P>0.05), and lymphocyte proliferation of the second stimulation (P>0.05) were
      similar to those of AB group. Histological observation of AC group showed that
      lymphocyte infiltration disappeared, cartilage and new bone formed, and bone
      marrow cavities emerged. A regraft experiment showed that CD4 T cell subsets
      (P<0.05) and lymphocyte proliferation of the second stimulation by splenic cell
      and bone supernatant of donor (P<0.05), BC group was significantly lower than
      those of BH group. So the immunological tolerance induced by CTLA4-Ig was of
      donor-specificity. CONCLUSION: The immunological tolerance induced by CTLA4-Ig
      was prolonged for 6 weeks. This study provides a brand-new path for bone
      transplantation, which can be helpful to other organ transplantation.

PMID- 15960445
TI  - [A modified arterial sleeve anastomosis in rat renal transplantation].
AB  - OBJECTIVE: To improve arterial anastomosis method for rat renal transplantation.
      METHODS: Renal transplantations were performed on 72 wistar rats. The donor
      superior mesenteric artery was end-to-end anastomosed to the recipient left renal
      artery by using of sleeve anastomosis technique. The external diameters of the
      vessels anastomosed were 0.60 +/- 0.05 mm (left renal artery) or 0.80 +/- 0.07 mm
      (superior mesenteric artery). The procedure consisted of a guiding suture and two
      fixing sutures. The guiding suture was used to "telescope" the recipient left
      renal artery into the donor superior mesenteric artery about 2 millimetre. Two
      fixing sutures were applied 180 degrees apart from each other and tied. Three
      sutures passed through all layers of the donor superior mesenteric artery and
      constricted the vessel lumen, but only penetrated the adventitia of the recipient
      left renal artery. RESULTS: The time for arterial anastomoses was approximately 6
      to 8 minutes. The renal grafts perfused very well after the recipient left renal
      artery clamp was removed. Complications included anastomotic hemorrhage (1 case)
      and thrombosis (1 case). Histologic examination of 34 grafts at different
      postoperative time ranging from 6 to 30 days revealed that renal artery was fully
      patent, with no evidence of ischemic injury. CONCLUSION: The modified arterial
      sleeve anastomosis technique is simple and feasible regardless of experimental
      condition and can be easily performed.

PMID- 15960446
TI  - [To reconstruct the blood supply of hepatic artery by a modified arterial
      "sleeve" anastomoses].
AB  - OBJECTIVE: To reconstruct the blood supply of hepatic artery of the recipient rat
      by a modified arterial "sleeve" anastomoses. METHODS: SD-SD and SD-Wistar rats
      liver transplantation were performed in 30 and 50 cases, respectively. The donor
      splenic artery, left gastric artery, right gastric artery and gastroduodenal
      artery were ligated, meanwhile the proper hepatic arteries were reserved. The
      celiac trunk of donors and the stump of right kidney artery of recipient were
      anastomosed by using 8-0 suture with "sleeve" technique. RESULTS: The mean time
      of artery anastomoses was 4.00 +/- 1.31 min. The rate of success was 96.3%. The
      longest survival time in the model SD-SD (29 survived) was more than 2 months. In
      SD-Wistar (48 survived), acute rejection was observed 3-5 days after operation
      and the mean survival time of rat was 9 d. CONCLUSION: The modified arterial
      "sleeve" anastomoses is an effective method to reconstruct blood supply of
      hepatic artery of rat recipient in rat liver transplantation.

PMID- 15960447
TI  - [Construction of the scaffold model from heterogeneous small blood vessels].
AB  - OBJECTIVE: To establish a scaffold model from heterogeneous small blood vessels.
      METHODS: Caudal arteries from 34 Wistar rats (average length 12.08 +/- 1.69 cm)
      were made into acellular blood vessel scaffolds. Some scaffolds were observed by
      electron microscope, and others were transplanted to the cut ends of ear central
      arteries of male Japanese big ear white rabbits. RESULTS: Average external
      diameter was 0.74 +/- 0.08 mm in proximal, and 0.55 +/- 0.08 mm in distal end of
      rat caudal arteries. The small blood vessel scaffolds had shin wall which was
      white and soft, composed of fibrous tissues without cells. On the intima surface
      the fibrous tissues were arrayed densely in a grid-like pattern. After
      transplantation, the blood flow was reserved, and kept flowing freely in 24
      hours. The pulsation of the transplanted artery was accessible and no blood
      leakage was found. CONCLUSION: The natural scaffolds are composed of fibrous
      tissues, and can sustain the artery pulse pressure for 24 hours. It is better to
      suture the blood vessels by sleeve anastomosis.

PMID- 15960448
TI  - [Review on the progress of peripheral nervous microelectrode].
AB  - OBJECTIVE: To review the progress and application of peripheral nervous
      microelectrode. METHODS: The recent articles on peripheral nervous microelectrode
      were extensively reviewed. The classification, the progress of the peripheral
      nervous microelectrode and its utilizable prospect in the control of electronic
      prosthesis were summarized. RESULTS: The microelectrodes had favorable functions
      of selective stimulation and recording. It provided an information transmitting
      interface between the electric prosthesis and peripheral nerves. CONCLUSION:
      Peripheral nervous signal is a feasible signal source to control electronic
      prosthesis.

PMID- 15960450
TI  - [Knowledge and re-evaluation of the prevention of endocarditis in dentistry].
AB  - Physicians, dentists and patients were questioned as to their knowledge of
      endocarditis prophylaxis. about three quarters of the physicians and about half
      of the dentists were able to judge the risk of endocarditis correctly. Removal of
      calculus was underestimated as a risk for bacteriemia by physicians and patients
      alike. dentists overestimated the risk for endocarditis in the group of "non-risk
      patients" (bypass), a fact resulting in an overdose/overuse of antibiotics.
      patients with lower education had less knowledge about the relation between their
      own personal risk and the necessary dental treatment.

PMID- 15960449
TI  - [The research progress of accelerating tendon healing and preventing tendon
      adhesion].
AB  - OBJECTIVE: To study the status quo of the methods and materials for accelerating
      the tendon healing and preventing the tendon adhesion as to provide an essential
      reference for future research and clinical application. METHODS: The recent
      articles on methods of accelerating tendon healing and preventing tendon adhesion
      were extensively reviewed. RESULTS: Tendon healing was decided by the co-effects
      of both endogenous and exogenous ways, and the former was more important. It was
      affected by the tendon sheath, vincula tendinum and synovial fluid as well.
      Tendon adhesion was mostly caused by excessive participation of exogenous healing
      factors and serious damage of the situations around the tendon. Tendon healing
      was accelerated by methods like repairing, reconstruction of peri-tendon tissues,
      electric stimulation, physiotherapy, adding herbs or growth factors, and gene
      intervention. Tendon adhesion was reduced or prevented by methods like the
      restoration of tendon sheath, using substitutions, adding herbs/drugs, and
      improving suturing techniques. CONCLUSION: Via the appropriate methods and
      techniques combining the Chinese traditional and modern medicine, tendon healing
      can be accelerated and the quality of tendon healing can be improved.

PMID- 15960451
TI  - [Critical assessment of microbiological diagnostics in periodontal diseases with
      special focus on Porphyromonas gingivalis].
AB  - Periodontitis is caused by an opportunistic infection with pathogenic
      microorganisms of the oral biofilm. In this paper, we discuss the usefulness of
      microbial diagnostics with respect to the differential diagnosis or the treatment
      approaches of periodontal diseases. Several diagnostic techniques, based on
      morphological, enzymatic, cultural, genetic or antigenetic properties have been
      established to analyze the microbial flora. Among the bacterial species some
      virulent genotypes of P. gingivalis play an important role in the etiology of
      periodontitis. Expression of fimbriae or different proteases have been identified
      as potential virulence factors of this gram negative anaerobic rod. To date a
      characterization of virulence of specific strains or a correlation between
      expression of different virulence factors and distinct periodontal conditions,
      however, is missing. Therefore, the importance of a routine identification of P.
      gingivalis still needs further evaluation.

PMID- 15960452
TI  - Obturation quality after four years of storage using the non-instrumentation
      technique.
AB  - The aim of this in vitro study was to compare the sealing quality of three root
      canal filling materials after four years of ageing. Obturation with the non
      instrumentation technique (NIT) was compared with cold lateral condensation of
      gutta-percha. Seventy-six canals were endodontically treated with traditional
      hand instrumentation and cold lateral condensation (control) whereas 77 canals
      were cleansed and obturated with NIT Three different sealers were used: AH 26, AH
      Plus and Apexit. After obturation, the teeth were stored for four years at 37
      degrees C. Coronal dye penetration was evaluated after the teeth were made
      transparent. The teeth cleansed and filled with the new method showed
      significantly less dye penetration than the hand-instrumented teeth (p < 0.001).
      Within the hand-obturated group, Apexit showed significantly more dye penetration
      (4.7 +/- 0.71 mm) (p < 0.01) than AH Plus (1.83 +/- 0.57 mm) or AH 26 (1.16 +/-
      0.4 mm). No significant differences were found within the NIT groups. This study
      showed NIT to produce root canal fillings with significantly less coronal leakage
      compared to the conventional technique after four years of storage in vitro.

PMID- 15960454
TI  - [The significance of heart-lunch machine in coronary bypass surgery].

PMID- 15960453
TI  - [Retrograde obturation with MTA Cement and Super-EBA after apicoectomy. Sealing
      ability of MTA and Super-EBA in dye penetration tests].
AB  - The present in vitro study investigated the sealing of retrograde fillings
      compounded of two different cements in consideration of cracking after root-end
      preparation of resected dental roots using diamond-coated ultrasonic retrotips.
      Root-end cavities were prepared in 32 resected roots using diamond-coated
      ultrasonic retrotips. The samples were divided into two groups. The first group
      was filled using zinc-oxide cement (Super-EBA-Cement), the second with mineral
      trioxide-aggregate (Pro Root MTA). After resection, root-end preparation and
      retrograde filling, the samples were analysed using macro-zoom photography and
      scanning electron microscopy. The sealing quality of the filling materials was
      detected through dye penetration test. The average degree of penetration of the
      samples filled with Super-EBA-Cement was 2.19 and of the samples filled with Pro
      Root MTA 0.44 respectively. Accordingly the sealing of Pro Root MTA in vitro is
      superior to the sealing of Super-EBA-Cement. Retrograde conditioning of resected
      roots with ultrasonic retrotips represents an efficient and sparing alternative
      to conventional root-end preparation techniques.

PMID- 15960455
TI  - [Coronary artery bypass surgery without the use of a heart-lunch machine].

PMID- 15960456
TI  - [Jimsonweed poisoning and the anticholinergic syndrome].

PMID- 15960457
TI  - [Accelerated course: high patient satisfaction and four days' hospitalisation in
      unselected patients with total hip and knee arthroplasty].

PMID- 15960458
TI  - [Treatment of ectopic pregnancies in Denmark].

PMID- 15960460
TI  - [The Danish Difficult Airway Registry (DDAR)].

PMID- 15960459
TI  - [B-Lynch suture, the surgical first choice for atonic postpartum hemorrhage after
      Cesarean section].

PMID- 15960461
TI  - [Inappropriate admissions to medical departments. Appropriateness Evaluation
      Protocol].

PMID- 15960462
TI  - [Patient information in medical departments].

PMID- 15960463
TI  - [A case of poisoning with jimsonweed and alcohol, taken with suicidal intent].

PMID- 15960464
TI  - [Severe metabolic acidosis after ingestion of ethylene glycol].

PMID- 15960465
TI  - [Liver rupture caused by fireworks].

PMID- 15960466
TI  - [Stump appendicitis after laparoscopic appendectomy].

PMID- 15960467
TI  - [Mendelian randomization].

PMID- 15960468
TI  - [End of the emergency psychological "crisis intervention" now?].

PMID- 15960469
TI  - [Who wants to produce drugs against prostatic cancer?].

PMID- 15960470
TI  - [Physicians' bacteria-contaminated hands are harmful for the patients].

PMID- 15960471
TI  - [The blind spot of the geriatrics].

PMID- 15960472
TI  - The new Z-drugs as sedatives and hypnotics.

PMID- 15960473
TI  - Occlusal splints.

PMID- 15960474
TI  - Agreeing to disagree.

PMID- 15960475
TI  - Antimicrobial substantivity of cavity disinfectants.
AB  - This study involved a comparative examination of different disinfectant solutions
      and their antimicrobial substantivity against Streptococcus mutans, Lactobacillus
      acidophilus, and Candida albicans. All of the disinfectants containing
      chlorhexidine and benzalkonium chloride demonstrated substantive antibacterial
      activity. Chlorhexidine-based solutions displayed the longest and most effective
      antimicrobial activity.

PMID- 15960476
TI  - Preventing sharps, splash, and needlestick injuries in dentistry: a comprehensive
      overview.
AB  - This article presents a comprehensive collection of precautions and suggestions
      for preventing sharps, splash, and needlestick injuries in dentistry. The authors
      looked at studies of sharps and splash injuries in dentistry to determine which
      of these injuries are most common. They then assembled a set of precautions to
      prevent these injuries based on published literature, tips learned from other
      dentists, and their own clinical observations. Dentists must remember and apply
      many precautions to prevent the broad spectrum of sharps and splash injuries that
      could occur during the delivery of dental care.

PMID- 15960477
TI  - A comparative study of two CEREC software systems in evaluating manufacturing
      time and accuracy of restorations.
AB  - This study compared the manufacturing times and the accuracy of proximal and
      occlusal contacts on restorations produced by two different versions of CEREC 3
      software, COS and 3D. Fourteen casts containing pre-existing inlay and onlay
      preparations of premolars and molars were mounted on articulators. A bite
      registration was made in maximum intercuspation. Optical impressions of the
      preparation and the bite registration were made. The Wilcoxon signed rank test
      was applied for a statistical analysis of time expended in the different design
      and manufacturing steps of both software versions. The chi-square test was
      applied for the statistical analysis of proximal and occlusal contacts.

PMID- 15960478
TI  - Using ParaPost Tenax fiberglass and ParaCore build-up material to restore
      severely damaged teeth.
AB  - This article describes a technique using ParaPost Tenax Fiber White, ParaPost
      Cement, and ParaPost ParaCore build-up material to restore a tooth with a
      significant loss of tooth structure. After successful root canal therapy, the
      posts were bonded in the canals and the core was built using ParaPost ParaCore
      build-up material. At that point, the tooth was prepared to receive a
      conventional porcelain-fused-to-metal crown.

PMID- 15960479
TI  - Influence of drinking patterns of carbonated beverages on dental erosion.
AB  - As a hard tissue dental disease, dental erosion has a multifactorial etiology.
      The majority of dental erosion that originates from extrinsic sources is the
      result of dietary intake, particularly acidic beverages. Several preventive means
      have been proposed to minimize the damage to the dentition, including a reduction
      in the consumption of causative beverages and the adoption of a specific method
      of drinking, utilizing a straw instead of a cup. This article presents two cases
      involving the clinical and radiographic features of erosion lesions associated
      with chronic and excessive intake of acidic carbonated beverages. These examples
      embody how drinking patterns influence the formation of erosion lesions in
      various anatomic locations within the dentition. The clinical and radiographic
      evidence presented in this report cautions against the use of nonspecific terms,
      such as "cup versus straw," and instead suggests implementing a more precise
      description of the suggested method. In view of the extensive damage inflicted by
      the chronic, excessive intake of carbonated beverages, preventive measures are
      considered to be the only effective course of management. This article offers
      illustrative examples of erosion lesions associated with long-term excessive
      intake of carbonated beverages. The influence of the drinking method--that is, a
      straw positioned into the labial vestibule versus a cup--on the anatomic location
      of the erosion lesions will be demonstrated through clinical and radiographic
      evidence.

PMID- 15960480
TI  - Severe localized periodontal destruction associated with cervical cemental
      separation.
AB  - Cemental separations and tears are secondary etiological factors that may lead to
      rapid periodontal destruction if the lesion communicates with the oral cavity and
      allows bacterial invasion. Although many cemental tears that occur on proximal
      surfaces can be diagnosed radiographically, separations on the facial or lingual
      surface that cannot be detected on radiographs may present a diagnostic dilemma.
      This article describes a case of lingual cemental separation on a maxillary
      incisor, with subsequent successful surgical correction utilizing an osseous
      graft.

PMID- 15960481
TI  - Gingival cyst of the adult: a case report.
AB  - The gingival cyst of the adult is an uncommon odontogenic cyst of developmental
      origin that is believed to represent the soft tissue counterpart of the lateral
      periodontal cyst. This article describes a case of gingival cyst of the adult,
      located in the alveolar mucosa on the facial aspect of the mandibular lateral
      incisor-canine region. The lesion was nodular with a sessile base, nonulcerated,
      and nonpainful; it was normal in color and measured 5.0 mm in diameter. An
      excisional biopsy was performed and surgical exploration revealed osseous surface
      erosion. Histopathological analysis confirmed the clinical hypothesis.

PMID- 15960482
TI  - Elder abuse update.
AB  - The following article offers an update on the topic of elder abuse. As the baby
      boomer generation ages, the number of elderly patients seeking all forms of
      dentistry will increase. This article is designed to inform dentists of their
      responsibility to the entire health of their patients. Guidelines and suggestions
      are made to ensure that dentists are able to diagnose and manage patients that
      may be in an abusive relationship.

PMID- 15960485
TI  - Radiolucency of the mandibular angle.

PMID- 15960484
TI  - Myers Briggs Type Indicator, burnout, and satisfaction in Illinois dentists.
AB  - There is conflicting research concerning satisfaction and burnout levels in
      dentistry. High levels of burnout can have deleterious effects on the dentist,
      his or her family, and patients. A random sample of Illinois general dentists was
      examined using the Myers Briggs Type Indicator, the Maslach Burnout Inventory,
      the Dentist Satisfaction Survey, and a demographic questionnaire. Areas examined
      were the frequency of types compared to a base population as well as the
      relationship of type to levels of satisfaction, burnout, and demographic items.
      Three of the 16 Myers Briggs types were overrepresented in this sample, while two
      types were underrepresented. Slightly less than half of the dentists were
      satisfied with their profession; 7.4% had reached significant levels of burnout
      and 83% perceived dentistry as being "very stressful." The personality types
      overrepresented in dentistry tended to have a higher level of satisfaction and a
      lower level of burnout compared to their cohort group.

PMID- 15960483
TI  - Acupuncture in the treatment of xerostomia: clinical report.
AB  - This article reviews the etiology and symptomatology of xerostomia and approaches
      for treating it, including the use of acupuncture. Seven xerostomia patients who
      were treated using acupuncture and the subsequent results of that treatment are
      discussed. Actual outcomes exceeded the author's expectations with all patients
      reporting an increase in salivary flow and the ability to eat and speak and
      improved sleep. Members of the dental team should consider referral for
      acupuncture as a viable adjunct when treating xerostomia. Dentists also might
      consider equipping themselves to provide such treatment in states that allow them
      to perform acupuncture.

PMID- 15960487
TI  - Personal reflections on receiving the Roger Adams Award in organic chemistry.
AB  - The author reflects on his early experiences as a chemist, and on the subsequent
      shift in emphasis that his research has undergone from mechanistic and synthetic
      organic chemistry to natural products chemistry. Finally, the extension of the
      field of natural products chemistry into the emerging discipline of chemical
      ecology is noted. This essay concludes with a consideration of the importance of
      including science in the curricula of all college and university students.

PMID- 15960486
TI  - Tongue lesion.

PMID- 15960488
TI  - A DFT study of Diels-Alder reactions of o-quinone methides and various
      substituted ethenes: selectivity and reaction mechanism.
AB  - The Diels-Alder (DA) reactions of various substituted ethenes (methyl vinyl ether
      (MVE), styrene, and methyl vinyl ketone (MVK)) with o-quinone methides (o-QM) are
      studied by means of density functional theory (DFT) at the B3LYP/6-31G(d,p)
      level. On the basis of analysis for frontier molecular orbital and comparison of
      the activation energies for different reaction pathways, the ortho attack modes
      present transition structures more stable than the meta ones. The reactivity,
      ortho selectivity, and asynchronicity are enhanced with the increase of the
      electron-releasing character of the substitute on ethene fragment. The
      discussions for the charge distribution and charge transfer on different
      transition states indicate that there are different molecular mechanisms for the
      different substituted ethenes. The calculations show that the effect of solvent
      decreases the activation energy and increases the asynchronicity. The results
      also indicate that the hydrogen-bond formation between chloroform and the
      carbonyl oxygen of the o-QM lowers the activation energies and increases the
      asynchronicity.

PMID- 15960489
TI  - An alpha-D-configured bicyclic nucleoside restricted in an E-type conformation:
      synthesis and parallel RNA recognition.
AB  - An alpha-D-arabino configured bicyclic nucleoside strongly restricted in an E
      type conformation by a 2'-3'-fused oxetane ring is synthesized. Several synthetic
      strategies toward the target compound are described, and the successful
      preparation from a D-xylose derivative is based on a ruthenium-mediated cleavage
      of a double bond, an S(N)2-inversion at the 2-position to give an arabino
      configuration, nucleobase coupling, and finally ring closure to give the oxetane
      ring. The E-type conformation is confirmed by molecular modeling and NMR. The
      nucleoside is incorporated into short alpha-DNA sequences. In a mixed pyrimidine
      context, these recognize complementary parallel RNA-sequences with mainly
      increased affinity and complementary parallel DNA-sequences with decreased
      affinity. The present bicyclic analogue represents the first conformationally
      restricted alpha-DNA-analogue to improve nucleic acid recognition in mixmers with
      alpha-DNA monomers.

PMID- 15960490
TI  - Matrix screening of substituted N-aryl-1,8-naphthalimides reveals new dual
      fluorescent dyes and unusually bright pyridine derivatives.
AB  - A 3 x 14 matrix of substituted N-aryl-1,8-naphthalimides was synthesized for the
      evaluation and discovery of dual fluorescence. Because of their unique
      photophysical properties, these dual fluorescent systems represent an exception
      to the widely studied TICT (Twisted Internal Charge Transfer) fluorescent dyes or
      tautomeric benzofluorescein class of two-color dyes. The matrix library was
      designed to investigate the effects of heterocycles, particularly pi-excessive
      and pi-deficient systems. Of the 42 compounds surveyed, five displayed well
      resolved two-color emission in solvents as nonpolar as hexane. Based on the
      observed trends in fluorescence lambda(max) and quantum yield, a new model is
      proposed that predicts LW and SW emission for these systems. In addition, this
      model provides potential design features for the synthesis of new dual
      fluorescent species.

PMID- 15960491
TI  - Nitrogen heterocyclic carbon-rich materials: synthesis and spectroscopic
      properties of dehydropyridoannulene macrocycles.
AB  - A new series of nitrogen heterocyclic dehydroannulenes 1-3 have been synthesized
      and their macrocyclic structures assigned using spectroscopic methods. The chiral
      and planar ground state conformations of 1 and 3, respectively, were determined
      by semiempirical theoretical calculations. All dehydropyridoannulenes and
      precursors possessing four aromatic rings functioned as fluorescent chromophores.
      A detailed spectroscopic investigation into the cation-binding properties of 3 in
      dilute solution revealed a particularly selective photoluminescence quenching
      sensory response for Pd(II) ions. Cycle 3, as well as 1 and 2, also exhibited
      reversible proton-triggered luminescence quenching behavior. At higher
      concentrations, 3 afforded a coordination polymer precipitate with Ag(I) ions.
      Cycles 1 and 2 and precursors 15, 23, and 29 also undergo thermochemical
      reactions that may potentially lead to carbon-rich polymers. The physicochemical
      properties of 1-3 suggest that dehydropyridoannulenes may serve as a particularly
      versatile new class of ligands for the creation of novel heteroatom-containing
      carbon-rich materials with many potential applications in supramolecular
      materials science and nanotechnology.

PMID- 15960492
TI  - An efficient and enantioselective approach to the azaspirocyclic core of
      alkaloids: formal synthesis of halichlorine and pinnaic acid.
AB  - A novel, highly stereoselective synthesis of an azaspirocyclic core, which
      contains four stereogenic carbons consistent with structures of natural
      halichlorine and pinnaic acid, is presented. Lipase PS-catalyzed selective
      acylation, asymmetric methylation on the alpha-methylene of the bicyclic lactone,
      and an asymmetric Michael addition of the tertiary nitro cyclopentane were
      concisely used to conquer the challenging problem of successfully constructing
      the C9 quarternary carbon center with complete stereocontrol. The spiropiperidine
      ring was formed by reduction of the delta-nitroketone, intramolecular
      condensation, and then highly stereoselective reduction of the cyclic nitrone
      with NaBH(4). This spirocyclic core is a key intermediate in Danishefsky's
      synthesis of pinnaic acid and halichlorine.

PMID- 15960494
TI  - Heterocyclic derivative syntheses by palladium-catalyzed oxidative cyclization
      alkoxycarbonylation of substituted gamma-oxoalkynes.
AB  - 4-Yn-1-ones containing different substituents, prop-2-ynyl alpha-ketoesters, and
      prop-2-ynyl alpha-ketoamides have been caused to react catalytically under
      oxidative carbonylation conditions to give tetrahydrofuran, dioxolane and
      oxazoline, dihydropyridinone, and tetrahydropyridinedione derivatives in
      satisfactory yields. Reactions were carried out in MeOH or MeCN/MeOH mixtures at
      65-100 degrees C in the presence of catalytic amounts of PdI(2) in conjunction
      with KI under 32 bar (at 25 degrees C) of a 3:1 mixture of CO and air. Anti and
      syn 5-exo-dig cyclization modes account for the formation of different products.
      It has been found that cyclopentenone, dihydropyridinone, and
      tetrahydropyridinedione derivatives, formed when the reaction is carried out at
      higher temperature and for a longer time, can also be selectively obtained
      through an acid treatment of tetrahydrofuran and oxazoline derivatives involving
      an unusual rearrangement. The structures of 6-methoxy-2,2-dimethyl-3-oxo-5-phenyl
      2,3-dihydropyridine-4-carboxylic acid methyl ester and 2,2,5-trimethyl-3,6-dioxo
      1,2,3,6-tetrahydropyridine-4-carboxylic acid methyl ester have been confirmed by
      X-ray diffraction analysis.

PMID- 15960495
TI  - Effect of o-methyl group on rate, mechanism, and resonance contribution:
      aminolysis of Y-substituted phenyl X-substituted 2-methylbenzoates.
AB  - Second-order rate constants have been determined spectrophotometrically for the
      reactions of 4-nitrophenyl X-substituted 2-methylbenzoates (2a-e) and Y
      substituted phenyl 2-methylbenzoates (3a-e) with alicyclic secondary amines in 80
      mol % H(2)O/20 mol % DMSO at 25.0 +/- 0.1 degrees C. The o-methyl group in the
      benzoyl moiety of 2a-e retards the reaction rate but does not influence the
      reaction mechanism. The Hammett plots for the reactions of 2a-e are nonlinear,
      while the corresponding Yukawa-Tsuno plots are linear with large r values (1.06
      1.70). The linear Yukawa-Tsuno plots suggest that stabilization of the ground
      state through resonance interaction between the electron donating substituent X
      and the carbonyl group is responsible for the nonlinear Hammett plots, while the
      large r values imply that the ground-state resonance interaction is significant.
      The reactions of 2a-e resulted in smaller rho(X) values but larger r values than
      the corresponding reactions of 4-nitrophenyl X-substituted benzoates (1a-e). The
      small rho(X) value for the reactions of 2a-e (e.g., rho(X) = 0.22) is suggested
      to be responsible for the large r value (e.g., r = 1.70). The reactions of 3a-e
      with piperidine are proposed to proceed in a stepwise manner with a change in the
      rate-determining step on the basis of the curved Bronsted-type plot obtained.
      Microscopic rate constants associated with the reactions of 3a-e are also
      consistent with the proposed mechanism.

PMID- 15960493
TI  - Convenient syntheses of dibenzo[c,p]chrysene and its possible proximate and
      ultimate carcinogens: in vitro metabolism and DNA adduction studies.
AB  - Dibenzo[c,p]chrysene (DB[c,p]C) is the only hexacyclic polycyclic aromatic
      hydrocarbon having two fjord regions, both in different chemical environments.
      Its environmental presence and relative tumorigenic potency are not known due to
      the lack of synthetic standards. We report here the synthesis of
      dibenzo[c,p]chrysene (1), its proximate carcinogens, i.e., trans-1,2-dihydroxy
      1,2-dihydro-DB[c,p]C (2) and trans-11,12-dihydroxy-11,12-dihydro-DB[c,p]C (3),
      and possible ultimate carcinogens, i.e., anti-trans-1,2-dihydroxy-3,4-epoxy
      1,2,3,4-tetrahydro-DB[c,p]C (4) and anti-trans-11,12-dihydroxy-13,14-epoxy
      11,12,13,14-tetrahydro-DB[c,p]C (5). The syntheses of 1 and the appropriately
      methoxy-substituted DB[c,p]C (12 and 27), key intermediates for the synthesis of
      its proximate and ultimate metabolites, were tried first using a Suzuki cross
      coupling reaction. However, the cyclization of olefins (10 and 11) gave poor
      yields of the desired products. An alternate method was thus developed employing
      a photochemical approach. The in vitro metabolism of DB[c,p]C was established
      with the S9 fraction of liver homogenate from phenobarbital/beta-naphthoflavone
      induced Sprague-Dawley rats. The major dihydrodiol formed was identified as the
      fjord region 11,12-dihydroxy-11,12-dihydro-DB[c,p]C, while the major and minor
      phenols were identified as 11-hydroxy-DB[c,p]C and 12-hydroxy-DB[c,p]C,
      respectively. Further, the DNA adduction studies with the calf thymus DNA led to
      a mixture of dA and dG adducts for both fjord region diol epoxides (4 and 5).
      Interestingly, the dA to dG ratio for 1,2-dihydroxy-3,4-epoxide was much higher
      (3.2) compared to that of 11,12-dihydroxy-13,14-epoxide (0.5).

PMID- 15960497
TI  - N-Tfa- and N-Fmoc-(alpha-aminoacyl)benzotriazoles as chiral C-acylating reagents
      under Friedel-Crafts reaction conditions.
AB  - Chiral N-Tfa- and N-Fmoc-protected (alpha-aminoacyl)benzotriazoles 1a-j undergo
      Friedel-Crafts-type reactions with indole, N-methylindole, pyrrole, N
      methylpyrrole, and benzene in the presence of AlCl(3) in efficient two-step
      sequences leading to enantiomerically pure alpha-amino N-heterocyclic ketones 2,
      3, 5, 6, and 7 or diketone 4. In the absence of a reactive partner, Phe- and Trp
      derivatives 1a, 1d undergo intramolecular cyclization to afford 12 and 13, again
      with retention of chirality.

PMID- 15960496
TI  - Synthesis and electrochemical and photophysical studies of tetrathiafulvalene
      annulated phthalocyanines.
AB  - The synthesis of tetrakis(tetrathiafulvalene)-annulated metal-free and
      metallophthalocyanines 5-8 via the tetramerization of the phthalonitrile
      derivative 4 is reported. All of them have been fully characterized by electronic
      absorption spectroscopy, thin-layer cyclic voltammetry, mass spectrometry, and
      elemental analysis. Their solution electrochemical data show two reversible four
      electron oxidation waves, indicating that these fused systems are strong pi
      electron donors, which give rise to tetra- or octaradical cation species. For the
      metal-free phthalocyanine 5, additionally a reversible one-electron wave was
      found in the negative direction arising from the reduction of the macrocycle.
      Moreover, the tetrathiafulvalene unit acts as an efficient reductive electron
      transfer quencher for the phthalocyanine emission, but upon its oxidation, an
      intense luminescence is switched on.

PMID- 15960498
TI  - Study on photochromism of diarylethenes with a 2,5-dihydropyrrole bridging unit:
      a convenient preparation of 3,4-diarylpyrroles from 3,4-diaryl-2,5
      dihydropyrroles.
AB  - Symmetric and nonsymmetric diarylethenes with a 2,5-dihydropyrrole bridging unit
      have been prepared, and the photochromic properties are investigated. Both
      symmetric and nonsymmetric diarylethenes with 2,5-dihydropyrrole bridging units
      undergo reversible ring-opening and ring-closing photoisomerization reactions in
      nonpolar solvents with UV/vis light, and some of them exhibit good fatigue
      resistance and no marked degradation detected after 10 cycles via an on/off
      switch. In polar solvents, however, photochromic diarylethenes with 2,5
      dihydropyrrole bridging units produce 3,4-diarylpyrrole derivatives instead of
      the ring-closing isomer of diarylethenes with UV light irradiation. A class of N
      substituted 3,4-diphenylethenes with 2,5-dihydropyrrole bridging units were
      prepared and used as templates to investigate the conversion reactions. The
      mechanism of photoconversion of 3,4-diaryl-2,5-dihydropyrroles to 3,4
      diarylpyrroles was explored as well.

PMID- 15960499
TI  - Synthesis of novel apio carbocyclic nucleoside analogues as selective a(3)
      adenosine receptor agonists.
AB  - On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine
      (apio-ddA), novel apio-neplanocin A analogues 5a-d, combining the properties of
      two nucleosides, were stereoselectively synthesized. The apio moiety of the
      target nucleosides 5a-d was stereoselectively introduced by treating lactol 10
      with 37% formaldehyde in the presence of potassium carbonate. The carbasugar
      moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs
      catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from
      the condensation of the glycosyl donor 14 with nucleic bases under the standard
      Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio
      methanocarbaadenosine 7 were derived from the common intermediate 13 using
      catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of
      the final nucleosides 5a-d, 6, and 7 did not show significant inhibitory activity
      against S-adenosylhomocysteine hydrolase (SAH) up to 100 muM, maybe due to the
      absence of the secondary hydroxyl group at the C3'-position, which should be
      oxidized by cofactor-bound NAD(+). However, apio-neplanocin A (5a) showed potent
      and highly selective binding affinity (K(i) = 628 +/- 69 nM) at the A(3)
      adenosine receptor without any binding affinity at the A(1) and A(2A) adenosine
      receptors. In conclusion, we have first developed novel carbocyclic nucleosides
      with unnatural apio-carbasugars using stereoselective hydroxymethylation and RCM
      reaction and also discovered a new template of human A(3) adenosine receptor
      agonist, which play a great role in developing new A(3) adenosine receptor
      agonist as well as in identifying the binding site of the receptor.

PMID- 15960500
TI  - Triphenylphosphine-mediated reductive cyclization of 2-nitrobiphenyls: a
      practical and convenient synthesis of carbazoles.
AB  - The synthesis of a series of substituted carbazoles from the corresponding 2
      nitrobiphenyl derivatives using a novel modification of the Cadogan reaction is
      described. Cyclization of the 2-nitrobiphenyls was achieved via reductive
      deoxygenation of the nitro groups using a slight excess of triphenylphosphine in
      a suitable solvent. We have observed a temperature dependence on the extent of
      conversion under these conditions, with higher boiling solvents affording higher
      yields across a range of substrates. The new reaction conditions are very
      straightforward and convenient to execute, tolerate a broad range of functional
      groups, and yield carbazole products in the absence of unwanted side products.

PMID- 15960501
TI  - Optically active seleninate esters: isolation, absolute configuration,
      racemization mechanism, and transformation into chiral selenoxide.
AB  - Optically active seleninate esters were obtained for the first time by
      chromatographic resolution on an optically active column. The absolute
      configurations of the optically active seleninate esters were determined by
      comparing their chiroptical properties with those of two analogous sulfinate
      esters, the absolute configuration of one of which is known and that of the other
      was determined by X-ray crystallographic analysis. The optically active
      seleninate esters were found to racemize in solution. Kinetic studies of the
      racemization, the oxygen exchange reaction with H(2)(18)O, and theoretical
      studies clarified that the racemization of the optically active seleninate esters
      in solution proceeded via an achiral hypervalent selenurane intermediate that was
      formed by the reaction with water. The reaction of the optically active
      seleninate ester and the sulfinate ester having bulky substituents with Grignard
      reagents was found to proceed with the retention of stereochemistry to give an
      optically active selenoxide and sulfoxides, respectively.

PMID- 15960503
TI  - Unsaturated selenacrown ethers: synthesis, structure, and formation of silver
      complexes.
AB  - The unsaturated selenacrown ethers, (Z,Z,Z,Z,Z)-1,4,7,10,13
      pentaselenacyclopentadeca-2,5,8,11,14-pentaene (15-US-5) (2), (Z,Z,Z,Z,Z,Z)
      1,4,7,10,13,16-hexaselenacyclooctadeca-2,5,8,11,14,17-hexaene (18-US-6) (3),
      (Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19-heptaselenacycloheneicosa-2,5,8,11,14,17,20
      heptaene (21-US-7) (4), (Z,Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19,22
      octaselenacyclotetracosa-2,5,8,11,14,17,20,23-octaene (24-US-8) (5), and
      (Z,Z,Z,Z,Z,Z,Z,Z,Z)-1,4,7,10,13,16,19,22,25-nonaselenacycloheptacosa
      2,5,8,11,14,17,20,23,26-nonaene (27-US-9) (6), were obtained together with 1,4
      diselenin (1) by reacting sodium selenide with cis-dichloroethene in the presence
      of a phase-transfer catalyst. The crystal structures of 2-5 were determined by X
      ray crystallographic analysis. The UV spectra of the selenacrown ethers showed
      absorption maximums in the range of 251-262 nm, which were assigned to n-->pi
      transitions. The cyclic voltammograms indicated that the large unsaturated
      selenacrown ethers were oxidized more easily than the small ones. The thermal
      reactions of the unsaturated selenacrown ethers afforded 1,4-diselenin (1) along
      with polymeric materials, whereas 1 was thermally stable even at 100 degrees C.
      The reactions of 1 or unsaturated selenacrown ethers 2-5 with silver ion yielded
      various novel silver complexes, Ag(C(4)H(4)Se(2))(CF(3)COO) (7),
      Ag(C(4)H(4)Se(2))(2)(CF(3)COO) (8), Ag(15-US-5)(CF(3)COO) (9), Ag(5)(18-US
      6)(3)(CF(3)COO)(5) (10), Ag(7)(21-US-7)(CF(3)COO)(5) (11), Ag(24-US
      8)(2)(CF(3)COO) (12), Ag(2)(24-US-8)(CF(3)COO)(2) (13), Ag(3)(24-US
      8)(2)(CF(3)COO)(3) (14), Ag(15-US-5)NO(3) (15), and Ag(21-US-7)BF(4) (16). The
      stoichiometry for the complexation with silver trifluoroacetate in solution was
      examined by (1)H NMR measurement. The titration plots of 2 and 5 under the
      dilution conditions showed a distinct inflection point at the 1/1
      metal/macrocycle ratio, whereas the plots of 1 and 3 showed gradual change.

PMID- 15960502
TI  - Isolation and characterization of phenyl viologen as a radical cation and neutral
      molecule.
AB  - The chemical synthesis, isolation, and characterization of phenyl viologen (PV)
      as a dication, radical cation, and neutral species are described. Single-crystal
      X-ray diffraction of PV(2+)2Cl(-.)2H2O and PV(.+)PF(6)(-).pyridine reveals the
      expected differences in bond lengths and also a structural change from two
      coplanar central rings in PV(.+) to a twist of 36 degrees between the two central
      rings in PV(2+). The phenyl viologen radical cation exhibits behavior
      characteristic of many radical cations, including weak pi-dimerization in the
      solid state and reversible pi-dimerization in solution. Electrical conductivity
      measurements of neutral phenyl viologen, the first such measurements of a neutral
      viologen, reveal that it is a significantly better conductor than the radical
      cation. Differences in geometric relaxation during charge transfer offer a
      possible explanation for the higher conductivity of the neutral viologen.

PMID- 15960504
TI  - A computational study on the mechanism for the chemical fixation of nitric oxide
      leading to 1,2,3-oxadiazole 3-oxide.
AB  - The chemical fixation of nitric oxide (NO) reacting with alkynyllithium to
      produce 5-methyl-3-oxide-1,2,3-oxadiazole has been investigated by using ab
      initio (U)MP2 and DFT/(U)B3LYP methods. The solvent effect was assessed using the
      combination of microsolvation model with explicit THF ligands on lithium and
      continuum solvent model based on the SCRF/CPCM method at the (U)B3LYP/6-31G*
      level. Our results reveal that the overall reaction is stepwise and considered to
      include two processes. In process 1, the nitrogen atom in nitric oxide at first
      attacks the C(1) atom in alkynyllithium to afford the intermediate 5. In process
      2, after another nitric oxide reacted with the intermediate 5 to produce 8a, we
      found that two pathways are involved. For path 1, the O(2) atom at first attacks
      the C(2) atom to form a five-membered ring geometry, and then lithium can rotate
      around the N(1)-O(1) bond, leading to the product 5-methyl-3-oxide-1,2,3
      oxadiazole followed addition of water. However, for path 2, lithium atom rotates
      first around the N(1)-O(1) bond, and then the product 5-methyl-3-oxide-1,2,3
      oxadiazole is also generated by addition of water. Our calculations indicate that
      path 1 is more favorable than path 2 in the gas phase, while both of them exist
      possibly in THF solvent. The overall reaction is exothermic.

PMID- 15960505
TI  - Controlling the outcome of an N-alkylation reaction by using N-oxide functional
      groups.
AB  - Covalent modifiers of proteins are of importance in chemical proteomics, an
      emerging chemical technology used to assign protein function. In this study, high
      field (1)H NMR techniques were used to analyze the reaction of the bioactive
      compound, 2,3-bis(bromomethyl)quinoxaline 1,4-dioxide, with amines (a model
      system for proteins containing nitrogen-based nucleophiles). Unexpectedly, the
      results show that a double nucleophilic substitution reaction involving 2 equiv
      of the amine is preferred to an intramolecular cyclization pathway. A direct
      comparison with the reaction carried out on a substrate lacking the N-oxide
      functional groups is also provided. X-ray crystal structures and computational
      studies are used to rationalize the observed differences in reactivity between
      the two systems.

PMID- 15960506
TI  - Dendrimers as photochemical reaction media. Photochemical behavior of
      unimolecular and bimolecular reactions in water-soluble dendrimers.
AB  - Synthesis and studies of poly(alkyl aryl ether) dendrimers, possessing carboxylic
      acid functionalities at their peripheries, are reported. 5-Bromopentyloxy
      methylisophthalate was utilized as the monomer to O-alkylate the phenolic
      hydroxyl groups of poly(alkyl aryl ether) dendrimers. Dendrimers of first,
      second, and third generations, possessing 6, 12, and 24 carboxylic acids,
      respectively, were thus prepared. These dendrimers were soluble in alkaline
      aqueous solutions, and the ensuing microenvironmental properties of the aqueous
      solutions were assessed by pyrene solubilization studies. Upon establishing the
      presence of nonpolar microenvironments within the dendritic structures,
      solubilizations of few organic substrates were conducted and their photochemical
      behaviors were assessed. Specifically, the photolysis of 1-phenyl-3-p-tolyl
      propan-2-one and benzoin ethyl ether and photodimerization of acenaphthylene were
      conducted. These studies revealed that the product distribution and the "cage
      effect" were more distinct and efficient for the third generation dendrimer, than
      for the first and second generation dendrimers. The photochemical studies of
      carboxylic acid functionalized dendrimers were compared to that of hydroxyl group
      terminated poly(alkyl aryl ether) dendrimers.

PMID- 15960507
TI  - Synthetic studies in the intramolecular carbocyclization of N-acyloxyiminium
      ions. Stereoelectronic and steric implications of nucleophilic alkene, alkyne,
      and allene tethers.
AB  - N-Acyloxyiminium ions generated from 4-substituted l-pyroglutamic esters with 4
      (3-butenyl), 4-(3-butynyl), 4-(3-cinnamylmethyl), and 4-allenic tethers undergo
      rapid Lewis acid mediated carbocyclization to give stereodefined azacyclic
      compounds depending on the nature of the nucleophilic tether. In general,
      reactions of alkenes and alkynes with terminal alkyl or aryl substituents, as
      well as allenes, proceed through transient vinylic carbocations that are attacked
      internally by the N-Boc group to give tricyclic dihydrooxazinones. Diastereotopic
      bis-4-(3-butenyl) and 4-(3-butynyl) tethers undergo stereochemically controlled
      attack favoring an antiperiplanar rather than synclinal approach to give
      enantiopure 6-halo octahydroindole-2-carboxylic acids and 6-halo hexahydroindole
      2-carboxylic acids as their methyl esters, respectively. The aza bicyclic and
      tricyclic compounds are excellent scaffolds for diversification.

PMID- 15960508
TI  - ROM polymerization-capture-release: application to the synthesis of unsymmetrical
      porphyrazinedithiols and peripherally metalated derivatives.
AB  - Crossover Linstead macrocyclization of a doubly norbornenyl-functionalized
      dimercaptomaleonitrile with dipropylmaleonitrile gave a crude mixture of
      porphyrazines containing the hexapropylporphyrazinedithiol magnesium complex. The
      mixture was subjected to ring-opening metathesis polymerization to yield the
      insoluble porphyrazinedithiol-functionalized polymers. Cleavage from the polymer
      backbone using mercury(II) acetate followed by reaction with electrophiles gave
      access to a range of thioporphyrazinedithiol derivatives including solitaire
      porphyrazines. Studies into the possible uses of hexapropyl-2,3-di
      (carboxymethylthio)porphyrazine in sensing metal cations in solution are
      described.

PMID- 15960509
TI  - The first fulleropyrrolidine derivative of Sc3N@C80: pronounced chemical shift
      differences of the geminal protons on the pyrrolidine ring.
AB  - The first pyrrolidine adduct on Sc(3)N@C(80) was synthesized and fully
      characterized. Addition of the N-ethylazomethine ylide occurs regioselectively on
      a [5,6] double bond on the surface of the icosahedral symmetry Sc(3)N@C(80),
      exactly in the same position as that described previously for a Diels-Alder
      adduct of the same compound.(11a,b) This addition pattern results in symmetric
      pyrrolidine carbons and unsymmetric geminal hydrogens on the pyrrolidine ring, as
      confirmed by (1)H and (13)C NMR spectroscopy, especially by HMQC. The shielding
      environment experienced by these geminal hydrogens differs by 1.26 ppm,
      indicative of pronounced ring current effects on the surface of this endohedral
      fullerene. This represents the first fully characterized pyrrolidine adduct on an
      endohedral metallofullerene.

PMID- 15960510
TI  - Stereolabile and configurationally stable atropisomers of hindered aryl
      carbinols.
AB  - Carbinols of the Ar-C(OH)R(2) type, Ar being o-isopropylphenyl, exist as
      stereolabile syn-clinal (sc) and anti-periplanar (ap) atropisomers when R = Me,
      Et, i-Pr. In the latter compound, the major atropisomer also comprises two
      enantiomeric forms that interchange with a barrier of 6.4 kcal mol(-1). X-ray
      diffraction, NOE experiments, and ab initio calculations indicate that the sc
      atropisomer is the more stable form when R = Me, i-Pr, t-Bu but is the less
      stable one when R = Et. NMR spectra at variable temperature allowed the
      determination of the barriers for the interconversion of the sc- into the ap
      atropisomers (DeltaG++ = 7.6, 8.8, and 13.5 kcal mol(-1) for Me, Et, i-Pr,
      respectively). When R is a tert-butyl group, the two atropisomers are
      configurationally stable: the ap-atropisomer is obtained as the kinetic
      controlled compound, which can be transformed into the thermodynamically more
      stable sc-atropisomer with a free energy of activation of 29.3 kcal mol(-1). Both
      atropisomers exhibit restricted rotation of the tert-butyl moiety, the
      corresponding DeltaG++ values being 9.4 and 8.8 kcal mol(-1) for the sc- and ap
      atropisomer, respectively.

PMID- 15960511
TI  - Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane:
      mechanistic comparators for artemisinin in the context of reaction pathways with
      iron(II).
AB  - Single electron reduction of the 1,2,4-trioxane heterocycle of artemisinin (1)
      forms primary and secondary carbon-centered radicals. The complex structure of 1
      does not lend itself to a satisfactory dissection of the electronic and steric
      effects that influence the formation and subsequent reaction of these carbon
      centered free radicals. To help demarcate these effects, we characterized the
      reactions of achiral dispiro-1,2,4-trioxolane 4 and dispiro-1,2,4-trioxanes 5-7
      with ferrous bromide and 4-oxo-TEMPO. Our results suggest a small preference for
      attack of Fe(II) on the nonketal peroxide oxygen atom of 1. For 4, but not for 5
      and 6, there was a strong preference for attack of Fe(II) on the less hindered
      peroxide bond oxygen atom. The steric hindrance afforded by a spiroadamantane in
      a five-membered trioxolane is evidently much greater than that for a
      corresponding six-membered trioxane. Unlike 1, 5-7 fragment by entropically
      favored beta-scission pathways forming relatively stable alpha-oxa carbon
      centered radicals. These data suggest that formation of either primary or
      secondary carbon-centered radicals is a necessary but insufficient criterion for
      antimalarial activity of 1 and synthetic peroxides.

PMID- 15960512
TI  - Solvation in electrospray mass spectrometry: effects on the reaction kinetics of
      fragmentation mediated by ion-neutral complexes.
AB  - In electrospray ionization (ESI) on a triple quadrupole mass spectrometer,
      benzydamine, a molecule with an N,N-dimethylaminopropoxyl side chain, showed a
      fragmentation pattern in Q1 scans that is dramatically different from the mass
      selected collision-induced dissociation (CID) of its MH(+) ion. The N,N
      dimethylimmonium ion, which dominates in Q1 scans at higher energies, is only a
      minor product in all CID spectra. By using a smaller model molecule, N,N,N',N'
      tetramethyl-1,3-propanediamine, with the kinetic energy release measured for the
      corresponding reaction, we have demonstrated that an ion-neutral complex composed
      of the N,N-dimethylazetidine cation and a neutral counterpart is involved. When
      the ion-neutral complex intermediate evolves toward elimination to form the
      immonium ion, the transition state is stabilized by the neutral species.
      Solvation of the ion-neutral complex, which obstructs the separation of the two
      partners by the resulting tighter enclosure, facilitates the elimination by
      enhancing the stabilization of the transition state. Therefore, the prevalence of
      the immonium ion in Q1 scans was a result of solvation in the ESI source. In CID
      reactions, where the decomposing ions are mass-selected and thus solvation does
      not exist, the immonium ion was a minor product, and the separation of the ion
      neutral complex became dominant.

PMID- 15960513
TI  - Utility of polymer-supported reagents in the total synthesis of lamellarins.
AB  - Four solid-supported reagents have been utilized in the multistep synthesis of
      lamellarins. The use of Amberlyst A-26 Br(3)(-) and polymer bound pyridine
      hydrobromide perbromide (PVPHP) for keto alpha-bromination of the less studied
      ortho-substituted acetophenone derivatives selectively furnished the
      corresponding monobromination products (phenacyl bromide derivatives), which were
      used directly in condensation reactions with benzyldihydroisoquinoline mediated
      by Amberlyst A-26 NaCO(3)(-). The 2H-pyrrole carbonates subsequently underwent
      intramolecular Friedel-Crafts transacylation followed by lactonization to provide
      the lamellarin skeleton. Alternatively, Amberlyst A-26 NaCO(3)(-) effectively
      served as base in condensation reaction of benzyldihydroisoquinoline with alpha
      nitrocinnamate derivatives to provide the corresponding 2-ethoxycarbonyl
      pyrroles, which smoothly underwent O-debenzylation reaction followed by
      lactonization to furnish the lamellarin skeleton. The novel Amberlyst-15 mediated
      lactonization reactions effectively combined the otherwise two separate steps
      into a single transformation.

PMID- 15960514
TI  - Synthesis of two-photon absorbing unsymmetrical branched chromophores through
      direct tris(bromomethylation) of fluorene.
AB  - Branched fluorene-based chromophores bearing electron-donating diphenylamino or
      electron-withdrawing nitro groups were synthesized as well as their linear
      analogues. An efficient synthetic method was developed via a novel 2,4,7
      tris(bromomethyl)-9,9-diethylfluorene intermediate. The bromomethyl groups in
      this key intermediate were converted to either phosphonate or carboxaldehyde
      moieties, facilitating preparation of a high functionality branched structure. It
      was found that the reactivity at position 4 is attenuated in the bromomethyl and
      phosphorylated derivates, facilitating the selective and systematic
      functionalization of the fluorenyl system. All compounds were stable up to ca.
      350 degrees C, except for a sterically crowded branched derivative. The linear
      optical properties of the compounds were investigated by UV-visible, steady-state
      fluorescence, and excitation anisotropy spectroscopic measurements. Fluorescence
      quantum yields were greater than or equal to 0.84 for symmetric linear and
      unsymmetric branched derivatives. Very high two-photon absorption (2PA) cross
      sections were achieved (5765 GM at 520 nm and 4194 GM at 570 nm), as determined
      with use of picosecond and femtosecond laser excitation sources, respectively.

PMID- 15960515
TI  - Copper-catalyzed cross-coupling of imines, acid chlorides, and organostannanes: a
      multicomponent synthesis of alpha-substituted amides.
AB  - A copper-catalyzed cross-coupling of organotin reagents with imines and acid
      chlorides is reported. The reaction proceeds efficiently with a range of vinyl-,
      alkyl-, aryl- and heteroaryl-substituted organostannanes as well as a diverse set
      of imines of non-enolizable aldehydes. Use of chloroformates also allows for the
      formation of N-protected alpha-substituted amines. This chemistry has been
      applied to the synthesis of isoquinoline alkaloid derivatives through the
      activation of cyclic imines.

PMID- 15960516
TI  - The cationic cascade route to longifolene.
AB  - W. S. Johnson's total synthesis of the sesquiterpenoid longifolene is a classic
      example of the power of cationic polycyclizations for constructing complex
      molecular architectures. Herein we revisit the key polycyclization step of this
      synthesis using hybrid Hartree-Fock/density functional theory calculations and
      validate the feasibility of Johnson's proposed mechanism. We also explore
      perturbations to the 3-center 2-electron bonding array in a key intermediate that
      result from changing the polycyclic framework in which it is embedded.

PMID- 15960517
TI  - Electron-transfer mechanism in the N-demethylation of N,N-dimethylanilines by the
      phthalimide-N-oxyl radical.
AB  - The reactivity of the phthalimide N-oxyl radical (PINO) toward the N-methyl C-H
      bond of a number of 4-X-substituted N,N-dimethylanilines (X = OMe, OPh, CF(3),
      CO(2)Et, CN) has been investigated by product and kinetic analysis. PINO was
      generated in CH(3)CN by reaction of N-hydroxyphthalimide (NHPI) with Pb(OAc)(4)
      or, for the kinetic study of the most reactive substrates (X = OMe, OPh), with
      tert-butoxyl radical produced by 266 nm laser flash photolysis of di-tert-butyl
      peroxide. The reaction was found to lead to the N-demethylation of the N,N
      dimethylaniline with a rate very sensitive to the electron donating power of the
      substituent (rho(+) = -2.5) as well as to the oxidation potential of the
      substrates. With appropriately deuterated N,N-dimethylanilines the intermolecular
      and intramolecular deuterium kinetic isotope effects (DKIEs) were measured for
      some substrates (X = OMe, CO(2)Et, CN) with the following results. First,
      intramolecular DKIE [(k(H)/k(D))(intra)] was found to be always different and
      higher than intermolecular DKIE [(k(H)/k(D))(inter)]; second, no intermolecular
      DKIE [(k(H)/k(D))(inter) = 1] was observed for X = OMe, whereas substantial
      values of (k(H)/k(D))(inter) were exhibited by X = CO(2)Et (4.8) and X = CN
      (5.8). These results, while are incompatible with a single step hydrogen atom
      transfer from the N-C-H bond to the N-oxyl radical, as proposed for the reaction
      of PINO with benzylic C-H bonds, can be nicely interpreted on the basis of a two
      step mechanism involving a reversible electron transfer from the aniline to PINO
      leading to an anilinium radical cation, followed by a proton-transfer step that
      produces an alpha-amino carbon radical. In line with this conclusion the
      reactivity data exhibited a good fit with the Marcus equation and a lambda value
      of 37.6 kcal mol(-1) was calculated for the reorganization energy required in
      this electron-transfer process. From this value, a quite high reorganization
      energy (>60 kcal mol(-1)) is estimated for the PINO/NHPI(-H)(-) self-exchange
      reaction. It is suggested that the N-demethylated product derives from the
      reaction of the alpha-amino carbon radical with PINO to form either a cross
      coupling product or an alpha-amino carbocation. Both species may react with the
      small amounts of H(2)O present in the medium to form a carbinolamine that, again
      by hydrolysis, can be eventually converted into the N-demethylated product.

PMID- 15960518
TI  - Preparation and electrophilic cyclization of multisubstituted dienamides leading
      to cyclic iminoethers.
AB  - Stereodefined multisubstituted dienamides could be concisely prepared in high
      yields by direct addition of 1-lithiobutadiene derivatives to both N-aryl and N
      alkyl isocyanates. Electrophilic cyclization of these dienamides was achieved to
      generate substituted cyclic iminoethers in excellent yields with perfect
      selectivity. When treated with 12 N aqueous HCl, dienamides underwent efficient
      and selective electrophilic cyclization to afford cyclic imidate derivatives.
      When treated with NBS, monobrominated or double-brominated cyclic iminoethers
      were formed.

PMID- 15960519
TI  - Reaction profiles and substituent effects for the reduction of carbonyl compounds
      with monomer and dimer simple metal hydride reagents.
AB  - Reaction profiles and energetics for the reactions of substituted benzaldehydes
      with a series of different simple metal hydrides (BH(3), BMeH(2), BMe(2)H,
      AlH(3), and AlMe(2)H) are examined computationally. B3LYP/6-31G optimizations and
      MP2/6-311G single point energy calculations revealed that the Al reagents are
      more reactive than B reagents. Replacement of H with Me on BH(3) or AlH(3) makes
      the reduction transition state (TS) less stable. Accordingly the overall
      reactivity is in the order AlH(3) > AlMe(2)H > BH(3) > BMe(2)H. The Hammett rho
      value for substituted benzaldehydes (BAs) is negative for the initial complex
      formation and positive for the hydride-transfer step. The size and the sign of
      the apparent rho value depend on the relative stabilities of the separated
      reactants and the complex. The TS structures vary according to the Hammond
      postulate for substituted BAs and the variation is reflected in carbonyl-carbon
      and aldehyde-deuterium isotope effects. Comparison of the reaction profiles of
      the monomer and dimer reagents reveals that the real reacting species is the
      monomer in the gas phase for BH(3) but the dimer for BMe(2)H.

PMID- 15960520
TI  - Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and
      amines or N-containing heterocycles.
AB  - CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic
      primary amines occurs at 40 degrees C under the promotion of N-methylglycine.
      Using l-proline as the promoter, coupling reaction of aryl iodides or aryl
      bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or
      electron-rich primary arylamines proceeds at 60-90 degrees C; an intramolecular
      coupling reaction between aryl chloride and primary amine moieties gives indoline
      at 70 degrees C; coupling reaction of aryl iodides with indole, pyrrole,
      carbazole, imidazole, or pyrazole can be carried out at 75-90 degrees C; and
      coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole
      occurs at 60-90 degrees C to provide the corresponding N-aryl products in good to
      excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction
      of electron-rich aryl bromides with imidazole or pyrazole to afford the
      corresponding N-aryl imidazoles or pyrazoles at 110 degrees C. The possible
      action of amino acids in these coupling reactions is discussed.

PMID- 15960521
TI  - A novel type of geosmin biosynthesis in myxobacteria.
AB  - The biosynthesis of geosmin (1) and (1(10)E,5E)-germacradien-11-ol (2), two
      volatile terpenoid compounds emitted by the myxobacteria Myxococcus xanthus and
      Stigmatella aurantiaca, was investigated in feeding experiments with different
      labeled precursors. In these experiments, the volatiles released by the cell
      cultures grown on agar plates were collected with a closed-loop stripping
      apparatus (CLSA) and analyzed by GC-MS. [(2)H(10)]Leucine and [4,4,4,5,5,5
      (2)H(6)]dimethylacrylate were fed to wild-type strains and bkd mutant strains,
      which are impaired in the degradation of leucine to isovaleryl-CoA.
      [(2)H(10)]Leucine was incorporated into 1 and 2 only by the wild-type strains via
      the biosynthetic pathway that involves leucine degradation and branching into the
      mevalonate pathway. Dimethylacrylyl-CoA (DMA-CoA) is an intermediate in the
      leucine degradation and in the recently discovered pathway from HMG-CoA to
      isovaleryl-CoA. The corresponding free acid, [4,4,4,5,5,5-(2)H(6)]dimethylacrylic
      acid, was incorporated into 1 and 2 only by the mutants impaired in leucine
      degradation. [4,4,6,6,6-(2)H(5)]Mevalonic acid lactone (12) was synthesized and
      fed to M. xanthus and S. aurantiaca wild-type strains and a double mutant strain
      of M. xanthus. This strain does not degrade leucine and is impaired in the
      reduction of 3-hydroxy-3-methylglutaryl-CoA to mevalonic acid. The mass spectral
      analysis of labeled 1 and 2 obtained in these feeding experiments led to a
      biosynthetic scheme to 1 with intermediate 2. This pathway differs from that
      observed in the liverwort Fossombronia pusilla and thus suggests microbial
      geosmin biosynthesis following a route different from that in liverworts. Our
      results are supported by a 1,2-hydride shift of the tertiary hydrogen atom at C
      4a into the ring opposite to that in F. pusilla.

PMID- 15960522
TI  - Convenient synthesis of N-methylamino acids compatible with Fmoc solid-phase
      peptide synthesis.
AB  - N(alpha)-Methylamino acid containing peptides exhibit interesting therapeutic
      profiles and are increasingly recognized as potentially useful therapeutics.
      Unfortunately, their synthesis is hampered by the high price and unavaibility of
      many N(alpha)-methylamino acids. An efficient and practical preparation of
      N(alpha)-methyl-N(alpha)-(o-nitrobenzenesulfonyl)-alpha-amino acids without
      extensive purification is described. The procedure is based on the well-known N
      alkylation of N(alpha)-arylsulfonylamino esters which was improved by using
      dimethyl sulfate and DBU as base. Ester cleavage is efficiently achieved by using
      an S(N)2-type saponification with lithium iodide, avoiding racemization observed
      with lithium hydroxide hydrolysis. Compatibility of the synthesized N(alpha)
      methylamino acids with Fmoc solid-phase peptide synthesis is demonstrated by
      using normal coupling conditions to efficiently prepare N-methyl dipeptides. The
      described procedure allows the preparation of N(alpha)-methylamino acids in a
      very short period of time and a rapid synthesis of N-methyl peptides using Fmoc
      solid-phase peptide synthesis.

PMID- 15960523
TI  - Deprotonation of benzoxazole and oxazole using lithium magnesates.
AB  - The first deprotonations of oxazole and benzoxazole using lithium magnesates are
      described. The reactions occurred in tetrahydrofuran at room temperature using
      1/3 equiv of lithium tributylmagnesate. As 2-lithiooxazole and 2
      lithiobenzoxazole, lithium tri(2-oxazolyl)magnesate and lithium tri(2
      benzoxazolyl)magnesate very rapidly and completely isomerized to the more stable
      2-(isocyano)enolate and 2-(isocyano)phenolate type structures, respectively, a
      result shown by NMR analysis. The isolation of 2-substituted oxazoles and
      benzoxazoles in medium to good yields after electrophilic trapping was
      interpreted in two ways: (1) the equilibration between the open and closed
      structures is faster than the trapping of the open isomers, and the closed
      isomers are more reactive than the open ones, or (2) the open isomers react with
      electrophiles in a intramolecular Passerini type reaction. The nonreactivity of
      the 2-(isocyano)enolate type structure toward anisaldehyde in the absence of
      lithium bromide makes the intramolecular Passerini type reaction more plausible.

PMID- 15960524
TI  - Studies on the synthesis of (+/-)-stenine: a combined intramolecular [4 + 2]
      cycloaddition/rearrangement cascade.
AB  - Several cyclic 2-(methylthio)-5-amidofurans containing tethered unsaturation were
      prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate
      (DMSTF) with beta-alkoxy-gamma-dithiane lactams. Thermolysis of these furans
      resulted in an intramolecular Diels-Alder reaction (IMDAF). The resulting oxa
      bridge cycloadducts underwent a subsequent 1,2-methylthio shift to form tricyclic
      lactams in high yield. Furan 9, annealed to an azepine ring, underwent the IMDAF
      reaction at or below room temperature. Conformational effects imposed by the
      placement of a carbonyl group within the tether, combined with a rotational bias
      about the C(2)-N bond, enhances the rate of the IMDAF reaction of the seven-ring
      system so that it occurs readily at 25 degrees C. The feasibility of using the
      cascade sequence in the context of a total synthesis of the Stemona alkaloid (+/
      )-stenine was explored. The eventual synthesis of (+/-)-stenine was carried out
      by an intramolecular Diels-Alder reaction of a 2-amido-5-methylthio-substituted
      furan containing a trans-pent-3-enoic acid methyl ester side chain in order to
      create the desired azepinoindole skeleton. This was followed by a series of
      reductions to set the syn-anti stereochemical relationship at the incipient ring
      fusion sites present in stenine. All six stereocenters at the azepinoindole core
      were derived in high stereoselectivity from the functionality present in the
      rearranged cycloadduct 10. Compound 10 was converted to stenine in 11 additional
      steps via a sequence that features a Crabtree's-catalyst directed hydrogenation,
      iodolactonization, and a Keck allylation.

PMID- 15960525
TI  - A new route to diverse 1-azasugars from N-Boc-5-hydroxy-3-piperidene as a common
      building block.
AB  - A new general method for the synthesis of a variety of 1-azasugars with a
      nitrogen atom at the anomeric position is described. The readily available chiral
      N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine
      (13), and 5'-deoxyisofagomine (14) via stereoselective epoxidation and
      regioselective ring-cleavage in a highly stereocontrolled manner. In addition,
      the synthesis of all four stereoisomers of 3,4,5-trihydroxypiperidines (18-21)
      classified as 1-azasugar-type glycosidase inhibitors was stereoselectively
      achieved from the (chiral) piperidene 3.

PMID- 15960526
TI  - Novel and efficient access to phenylamino-pyrimidine type protein kinase C
      inhibitors utilizing a Negishi cross-coupling strategy.
AB  - A novel, short, and efficient synthetic pathway to 3-{4-[2-(3-chlorophenylamino)
      pyrimidin-4-yl]-pyridin-2-ylamino}-propanol (CGP 60474) and a series of analogues
      was developed. The synthetic sequence consisted of a Negishi-type cross-coupling
      reaction in the key step followed by two subsequent nucleophilic substitution
      reactions. This strategy represents a versatile and robust protocol to access
      diverse analogues of the title compound for subsequent SAR studies as potential
      phenylamino-pyrimidine type protein kinase C inhibitors.

PMID- 15960528
TI  - Lewis base catalyzed, enantioselective aldol addition of methyl trichlorosilyl
      ketene acetal to ketones.
AB  - The catalytic enantioselective addition of an acetate enolate equivalent to
      ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide
      range of ketones in the presence of pyridine N-oxide to afford the aldol addition
      products in excellent yields. Chiral 2,2'-pyridyl bis-N-oxides bearing various
      substituents at the 3,3'- and 6,6'-positions also provide excellent yields of the
      aldol products with variable enantioselectivities ranging from 94/6 er for
      aromatic ketones to nearly racemic for aliphatic ketones. An X-ray crystal
      structure of the complex between a catalyst and silicon tetrachloride (((P)-(R,R)
      19.SiCl(4))) has been obtained. Extensive computational analysis provides a
      stereochemical rationale for the observed trends in enantioselectivities.

PMID- 15960527
TI  - Diels-Alder reactions of N-acyl-2-alkyl(aryl)-5-vinyl-2,3-dihydro-4-pyridones.
AB  - Readily available N-acyl-5-vinyl-2,3-dihydro-4-pyridones undergo Diels-Alder
      cyclization with various dienophiles to afford novel octahydroquinolines
      containing synthetically useful functionality. With dihydropyridone 5 and cis
      disubstituted dienophiles, the resulting cycloadducts were obtained as single
      diastereomers in good to excellent yield. The corresponding reaction of 5 with
      methyl acrylate, acrylonitrile, and phenyl vinyl sulfone showed modest preference
      for the endo adducts. The effect of the dihydropyridone C-2 and C-4 substituents
      on the degree of diastereofacial control was examined. By using this methodology,
      the core decahydroquinoline skeleton of gephyrotoxin was prepared in a
      stereocontrolled fashion. Interesting reactivity was observed with certain
      dienophiles leading to ring-opening of the initially formed cycloadducts. This
      tandem reaction provides a route to uniquely substituted beta-aminoketones,
      alcohols, and unnatural amino acids.

PMID- 15960529
TI  - From C-glycosides to pyranopyrans: an approach to thyrsiferol using titanium(III)
      promoted redox couplings.
AB  - An approach to the pyranopyran ring system that is found in many natural
      products, including thyrsiferol, is described. The route entails the assembly of
      an alpha,beta-unsaturated ketone (11) from geraniol and dihydropyran (23) from
      acetyl acetaldehyde dimethyl acetal (19) and their titanium(III)-promoted
      coupling to afford a respectable 60% yield of keto alcohol 26. The sigma-bond
      formed in this process corresponds to the pro-C(9)-C(10) bond of thyrsiferol (4).
      Attempts to invert the stereochemistry at the pro-C(11) center were thwarted by
      the congestion imparted by the presence of the vicinal TBS-ether. Consequently,
      cyclization of the coupling adduct under conditions developed by Olah and Prakash
      and co-workers led to the cis-fused pyranopyran 27. X-ray analysis of this
      crystalline material confirmed each of the stereochemical assignments. After much
      effort, it was determined that the hydroxyl group at C(12) could be removed by
      treating the derived methyl xanthate with a tri-n-butylphosphine-borane complex
      under radical-forming conditions. The reaction sequence worked well, despite the
      hindered working environment and the presence of a potentially labile C-Br bond.

PMID- 15960530
TI  - Highly stereoselective one-pot procedure to prepare bis- and tris-chalcogenide
      alkenes via addition of disulfides and diselenides to terminal alkynes.
AB  - We present here the reaction of diorganoyl dichalcogenides with terminal alkynes
      under catalyst-free conditions, by a one-pot procedure, to prepare bis- and tris
      chalcogenide alkenes selectively, avoiding the previous preparation of chalcogen
      alkynes. The reaction proceeded cleanly under mild reaction conditions, and the
      addition of dichalcogenides to alkynes occurred stereoselectively to give
      exclusively the corresponding Z isomers. We observed that the selectivity control
      was governed by the effective participation of the hydroxyl group from propargyl
      alcohols. In addition, the bis-chalcogenide alkenes were exclusively obtained
      with propargyl alcohol having the acidic hydroxyl group proton. Conversely, the
      alkynes with no potentially acidic hydroxyl group proton, at propargyl positions,
      gave exclusively the tris-chalcogenide alkenes.

PMID- 15960531
TI  - Study of the ESI-mass spectrometry ionization mechanism of Fischer carbene
      complexes.
AB  - By means of deuterium-labeling experiments, we have carried out a systematic ESI
      MS study to determine the mechanism of ESI ionization of alkenyl and alkynyl
      group 6 Fischer carbene complexes. These compounds can be ionized under ESI
      conditions only in the presence of additives such as hydroquinone (HQ) or
      tetrathiafulvalene (TTF). Our results demonstrate that in the ESI source an anion
      radical is formed after the initial HQ- or TTF-mediated electron transfer to the
      metallic carbene complex. For alkenyl carbene complexes, this species evolves by
      extrusion of a hydrogen radical to form an allenylchromium anion that is detected
      as the [M - H](-) ion in the mass spectrum. The preference for this mechanistic
      pathway could be rationalized by DFT calculations. In the case of alkynyl carbene
      complexes, experiments combining deuterated substrate, additive, and solvent
      demonstrate that the previously proposed allene-anion carbene complex is not
      formed. Instead, the H transfer from the ethoxy group in the anion radical,
      followed by extrusion of a hydrogen radical, leads to an allenyl anion that is
      detected in the ESI-MS as [M - H - CO](-).

PMID- 15960532
TI  - Proximal regioselectivity of the O,O'-dialkylation of
      tetrahydroxyketocalix[4]arene.
AB  - The only dialkylated products obtained in the reaction of
      tetrahydroxyketocalixarene 2a with MeI/K(2)CO(3) or PhCH(2)Br/K(2)CO(3) are the
      corresponding proximal (i.e., 1,2) O,O'-dialkyl ethers, in contrast to the parent
      tetrahydroxycalix[4]arene 1a which affords the distal (1,3) dialkyl ether
      derivatives. Pairs of geminally alkylated phenoxy groups in the conformationally
      rigid dibenzylated and tetrabenzylated derivatives are oriented in an anti
      fashion. These results can be rationalized assuming that the 1,3-alternate
      arrangement of the rings preferred by 2a is adopted during all the intermediate
      stages of the alkylation. The NMR spectra (in CDCl(3)) of the monomethyl,
      dimethyl, trimethyl, and tetramethyl ether derivatives of 2a are in agreement
      with a 1,3-alternate conformation.

PMID- 15960533
TI  - Diphenylnitrenium ion: cyclization, electron transfer, and polymerization
      reactions.
AB  - Reactions of diphenylnitrenium ion were examined using laser flash photolysis
      (LFP), product analysis, and computational modeling using density functional
      theory (DFT). In the absence of trapping agents, diphenylnitrenium ion cyclizes
      to form carbazole. On the basis of laser flash photolysis experiments and DFT
      calculations it is argued that this process is a concerted cyclization/proton
      transfer that forms the H-4a tautomer of carbazole. Additional LFP experiments
      and product studies show that diphenylnitrenium ion reacts with electron-rich
      arenes (e.g., N,N-dimethylaniline, diphenylamine, and carbazole) through an
      initial one-electron transfer. The radical intermediates formed in this step then
      couple to form dimeric products. Secondary reactions between the
      diphenylnitrenium ion and these dimers results in the formation of oligomeric
      materials.

PMID- 15960535
TI  - Unexpected halogen substituent effects on the complex thermal relaxation of
      naphthopyrans after UV irradiation.
AB  - The kinetics of the thermal fading of four halogenated naphthopyrans (NP) have
      been analyzed using NMR spectroscopy in CD(3)CN. Two photomerocyanines (TT and
      TC) were detected after UV irradiation. The main relaxation process TC --> NP was
      coupled with TT/TC isomerization. The activation parameters of the various
      processes were rationalized by considering electronegativity and polarizability
      of the halogen substituents and their selective solvation by the electronegative
      nitrogen of acetonitrile.

PMID- 15960534
TI  - "Matched/mismatched" diastereomeric dirhodium(II) carboxamidate catalyst pairs.
      Structure-selectivity correlations in diazo decomposition and hetero-Diels-Alder
      reactions.
AB  - Homo-ligated dirhodium(II) carboxamidates provide well-defined structural
      frameworks with which to investigate catalyst-controlled multiple asymmetric
      induction ("match/mismatch" effects). Diastereomeric pairs of methyl 2
      oxoimidazolidine-4(S)-carboxylate ligands containing 2-phenylcyclopropane
      (4S,2'S,3'S-HMCPIM and 4S,2'R,3'R-HMCPIM) and N-benzenesulfonylproline (4S,2'S
      HBSPIM and 4S,2'R-HBSPIM) attachments at the 1-N-acyl site have been prepared;
      the resulting (cis-2,2)-Rh(2)L(4) compounds have been produced in good yields,
      and the X-ray crystal structure of each dirhodium(II) compound has been obtained.
      The incorporation of additional stereocenters into the dirhodium(II) ligands
      leads to recognizable levels of double asymmetric induction for C-H insertion,
      cyclopropanation, and hetero-Diels-Alder cycloaddition applications. The
      configurationally "matched" cases provide modest increases in enantioselectivity
      for intramolecular C-H insertion reactions relative to the model catalyst
      Rh(2)(MPPIM)(4), but applications of the configurationally mismatched catalysts
      result in significant lowering of enantioselectivity. The Rh(2)(BSPIM)(4)
      catalysts show the highest degree of differential selectivity. Hetero-Diels-Alder
      reactions show inverse behavior from the configurationally matched and mismatched
      Rh(2)L(4) catalysts to that found in the metal carbene transformations.

PMID- 15960536
TI  - Enhanced peptide beta-sheet affinity by metal to ligand coordination.
AB  - A histidine-coordinating metal complex substituted with methoxypyrrole amino
      acids (MOPAS) as a peptide beta-sheet binder shows high affinity for a H(2)N-His
      Leu-Leu-Val-Phe-OMe pentapeptide in DMSO solution. Within the complex, a beta
      sheet conformation is induced into the pentapeptide by weak intra-assembly
      interactions with the MOPAS units.

PMID- 15960537
TI  - 7:8,9:10-dibenzo-1,2,3,4-tetrafluoro- triphenylene: synthesis, structure, and
      photophysical properties of a novel [5]helicene.
AB  - A simple and efficient synthesis and crystallographic analysis of the partially
      fluorinated 7:8,9:10-dibenzo-1,2,3,4-tetrafluorotriphenylene, 1, in 59% yield is
      reported. Compound 1 is a blue luminescent [5]helicene in both solution and the
      solid state. It spontaneously forms enantiomorphous single crystals from racemic
      samples and exhibits slipped, face-to-face F...C(pi) contacts within the stacks
      of molecules.

PMID- 15960538
TI  - A convenient 3-step synthesis of (R)-7-hydroxycarvone from (S)-alpha-pinene.
AB  - A convenient 3-step synthesis of (R)-7-hydroxycarvone (2) has been developed
      starting from (S)-alpha-pinene (7), using photooxygenation, oxidation, and
      fragmentation reactions. An improved synthesis of epoxy alcohol 6 and an unusual
      Ti(OiPr)(4) catalyzed hydroxy epoxide to keto alcohol rearrangement are also
      described.

PMID- 15960540
TI  - Novel synthesis of gem-dichloroaziridines from imines via the KF/Al2O3-promoted
      generation of dichlorocarbene from chloroform.
AB  - KF/Al(2)O(3) was found to be an efficient base for the reaction of imines with
      chloroform in acetonitrile to give gem-dichloroaziridines 2 in moderate to high
      yields. The KF/Al(2)O(3)-promoted dichloroaziridination can be carried out with
      simple workup, tolerates a variety of functional groups present in the imines,
      and proceeds smoothly with a smaller amount of carbene source.

PMID- 15960539
TI  - Versatile use of ytterbium(III) triflate and acid washed molecular sieves in the
      activation of glycosyl trifluoroacetimidate donors. Assemblage of a biologically
      relevant tetrasaccharide sequence of Globo H.
AB  - The nonreducing tetrasaccharide terminus of Globo H has been assembled in good
      yield and excellent stereocontrol exclusively by using mild and moisture stable
      agents such as Yb(OTf)(3) and acid washed molecular sieves for the activation of
      glycosyltrifluoroacetimidate donors in the glycosylation steps.

PMID- 15960541
TI  - Mechanistic diversity of the van Leusen reaction applied to 6-ketomorphinans and
      synthetic potential of the resulting acrylonitrile substructures.
AB  - Tosylmethyl isocyanide was used to convert 7,8-didehydro-6-ketomorphinans to 6,7
      didehydromorphinan-6-carbonitriles with retainment of the 4,5-epoxy ring.
      However, ring opening occurred in the presence of NaH giving 5,6,7,8
      tetradehydromorphinan-6-carbonitriles. Addition of nucleophiles such as Li
      diisopropylamide or Grignard reagents to the acrylonitrile substructure yielded
      ring-opened 5,6-didehydro products. Seven products were characterized by X-ray
      crystal structure analysis and revealed insight into the mechanistic diversity of
      the van Leusen reaction.

PMID- 15960542
TI  - Elimination reactions of N-alkyl-N-chlorothenylamines promoted by MeONa-MeOH and
      Et(2)NH-MeCN. Effect of the beta-aryl group on the imine-forming transition
      state.
AB  - Elimination reactions of N-alkyl-N-chlorothenylamines 1-4 with MeONa-MeOH and
      Et(2)NH-MeCN have been studied kinetically. The elimination reactions are
      regiospecific, producing only the conjugated imines. The reactions are second
      order and exhibit substantial values of Hammett rho and k(H)/k(D), and an E2
      mechanism is evident. The relative rates of elimination for Me/Et/i-Pr/t-Bu
      substituents are 1/0.5/0.2/0.02 with MeONa-MeOH and 1/0.4/0.2/0.06 with Et(2)NH
      MeCN. The transition state structure changes toward more product-like as the base
      is changed from MeONa-MeOH to Et(2)NH-MeCN. Comparison with existing data reveals
      that the structure of the transition state is relatively insensitive to the beta
      aryl group variation.

PMID- 15960543
TI  - Hantzsch synthesis of pyrazolo[1',2':1,2]pyrazolo[3,4-b]pyridines: partial
      agonists of the calcitonin receptor.
AB  - Small molecule calcitonin receptor agonists are of potential utility in the
      treatment and prevention of osteoporosis. Bicycloeneamine 1 was a useful
      intermediate in the synthesis of pyrazolopyridine calcitonin receptor partial
      agonists 2a-f. Dihydropyridines 10a-c were conveniently prepared by reaction of 1
      with Knoevenagel adducts 9a-c, or in the case of 10d, by a three component
      reaction with 1, beta-ketoester 7b, and aldehyde 8c. Oxidation of 10a-d to
      pyridines 11a-d and subsequent amide formation afforded the title compounds.

PMID- 15960544
TI  - The reaction of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with carbon dioxide.
AB  - Amidines have been reported to react with CO(2) to form a stable and isolable
      zwitterionic adduct but previous studies were performed in the presence of at
      least some water. However, spectroscopy of the reaction between DBU and CO(2)
      detects the rapid formation of the bicarbonate salt of DBU when wet DBU is
      exposed to CO(2) and does not indicate that an isolable zwitterionic adduct
      between DBU and CO(2) forms either in the presence or the absence of water.

PMID- 15960545
TI  - Synthesis of (+)-conagenin.
AB  - An efficient total synthesis of (+)-conagenin was achieved. The right fragment of
      conagenin, alpha-methylserine containing a quaternary stereocenter attached to
      nitrogen, was synthesized using allyl cyanate-to-isocyanate rearrangement. The
      left fragment, 2,4-dihydroxy-3-methylpentanoic acid, has three contiguous
      stereogenic centers, which was efficiently constructed by enantioselective
      monoreduction of 2-alkyl-1,3-diketones reported by Cossy, and chelation
      controlled stereoselective reduction of beta-hydroxy ketone. These two fragments
      were coupled through intramolecular amide bond formation with high efficiency.

PMID- 15960546
TI  - Synthesis of tertiary benzamides via Pd-catalyzed coupling of arylboronic esters
      and carbamoyl chlorides.
AB  - Ortho-substituted arylboronic esters are efficiently coupled with carbamoyl
      chlorides under Pd-catalysis to give tertiary benzamides.

PMID- 15960547
TI  - Palladium-catalyzed synthesis of alpha-iminoamides from imidoyl chlorides and a
      carbamoylsilane.
AB  - A series of pure imidoyl chlorides were converted into alpha-iminoamides by
      treatment with a carbamoylsilane under catalysis by palladium(0) complexes.

PMID- 15960548
TI  - Efficient and reusable PdCl2(MeCN)2/CuCl2/PEG-400 system for cyclization of
      alkenyl beta-keto esters and amides.
AB  - PEG-400 [poly(ethylene glycol-400)] was found as an effective medium for the
      PdCl(2)(MeCN)(2)-catalyzed hydroalkylation cyclization of alkenyl beta-keto
      esters and amides. In PEG-400, no additives such as Me(3)SiCl and Ln(OTf)(3) were
      required for the complete conversion of alkenyl beta-keto esters. The results
      also showed that CuCl(2) could promote the reaction. In the presence of
      PdCl(2)(MeCN)(2), CuCl(2), and PEG-400, various alkenyl beta-keto esters and
      amides underwent a selective cyclization reaction to give good to excellent
      yields of the desired six-membered-ring carbocycles. Furthermore, the
      PdCl(2)(MeCN)(2)/CuCl(2)/PEG-400 system could be recycled and reused five times
      without any loss of catalytic activity.

PMID- 15960550
TI  - Incorporation of uncertainty in health economic modelling studies.
AB  - In a recent leading article in PharmacoEconomics, Nuijten described some methods
      for incorporating uncertainty into health economic models and for utilising the
      information on uncertainty regarding the cost effectiveness of a therapy in
      resource allocation decision-making. His proposals are found to suffer from
      serious flaws in statistical and health economic reasoning.Nuijten's suggestions
      for incorporating uncertainty: (a) wrongly interpret the p-value as the
      probability that the null hypothesis is true; (b) represent this probability
      wrongly by truncating the input distribution; and (c) in the specific example of
      an antiparkinsonian drug uses a completely inappropriate p-value of 0.05 when the
      null hypothesis would, in reality, be emphatically disproved by the data.His
      suggestions regarding minimum important differences in cost effectiveness: (a)
      introduce areas of indifference that suggest inappropriate reliance on cost
      minimisation while failing to recognise that decisions should be based on
      expected costs versus benefits; and (b) offer no guidance on how the
      probabilities associated with these areas could be used in decision-making.
      Furthermore, Nuijten's model for Parkinson's disease is over-simplified to the
      point of providing a bad example of modelling practice, which may mislead the
      readers of PharmacoEconomics. The rationale for this paper is to ensure that
      readers do not apply inappropriate analyses as a result of following the
      proposals contained in Nuijten's paper. In addition to a detailed critique of
      Nuijten's proposals, we provide brief summaries of the currently accepted best
      practice in cost-effectiveness decision-making under uncertainty.

PMID- 15960551
TI  - Health utilities in Alzheimer's disease and implications for cost-effectiveness
      analysis.
AB  - The National Institute for Health and Clinical Excellence (NICE) provisional
      decision against memantine and other medications for Alzheimer's disease (AD) has
      generated much discussion. In its decision, NICE expressed concern about the data
      source used for the utility scores in the industry submission of the memantine
      model. NICE therefore turned to an alternative data source. However, in doing so,
      it made the key assumption that moderate-to-severe AD patients living in the
      community were independent. Furthermore, the NICE data source also had its
      limitations. There are numerous limitations in inferring from available data how
      utilities vary between dependent and non-dependent patients with AD. Most
      importantly, we lack direct evidence from primary data. Nonetheless, it seems
      reasonable to assume that patients with severe AD, and likely those with moderate
      AD as well, have full-time care needs, regardless of their setting. The NICE
      assumption that they do not results in a difference in utilities between
      dependent and non-dependent AD individuals of only 0.06. This seems to be at the
      low end of what one would consider a reasonable estimate.

PMID- 15960552
TI  - The economics of topical immunomodulators for the treatment of atopic dermatitis.
AB  - Atopic dermatitis is a common, chronic, relapsing inflammatory skin disease
      frequently affecting infants and children. The worldwide prevalence of atopic
      dermatitis is estimated to be 5--20% of the paediatric population. First-line
      therapy has generally consisted of dry skin care, avoidance of triggers,
      application of topical corticosteroids, and administration of antihistamines and
      oral antibacterials. Topical corticosteroids improve the lesions of atopic
      dermatitis; however, concern on the part of physicians and patients regarding
      adverse effects has led to reluctance to utilise topical corticosteroids early
      and especially for prolonged periods. Topical immunomodulators (TIMs), including
      tacrolimus ointment and pimecrolimus cream, were recently introduced for the
      treatment of atopic dermatitis. Clinical data show that TIMs are effective in
      atopic dermatitis, yet do not cause the significant adverse effects associated
      with topical corticosteroids. Questions remain regarding the place of TIMs as a
      treatment for atopic dermatitis and how to use them most effectively, from both
      therapeutic and pharmacoeconomic standpoints. Specifically, two major issues
      remain unresolved: (i) how TIMs measure up to other therapies, especially topical
      corticosteroids; and (ii) how members of the TIM drug class compare against each
      other. Previous research has established that atopic dermatitis has a significant
      impact on quality of life (QOL) and carries a substantial economic burden. Some
      studies have also measured the utility of various atopic dermatitis disease
      states. While there is a need for further research, early economic studies
      provide evidence that TIMs positively affect the QOL of patients and families. In
      certain patients, TIMs may be cost effective and have an acceptable incremental
      cost utility compared with topical corticosteroids.Making cost-effectiveness
      comparisons between tacrolimus and pimecrolimus is challenging because there are
      limited head-to-head comparative data. Given currently available efficacy data,
      the results of one study suggest that tacrolimus may be more cost effective than
      pimecrolimus in paediatric patients with moderate atopic dermatitis. The full
      economic and QOL benefits of both agents are yet to be completely understood. The
      studies reviewed herein are the first to delineate the pharmacoeconomic benefits
      of TIMs in atopic dermatitis, and lay the foundation for future analyses. TIMs
      represent an exciting advance in the treatment of atopic dermatitis. Additional
      research will help determine the proper place of TIMs among the current array of
      therapeutic options for atopic dermatitis.

PMID- 15960553
TI  - Remission from depression : a review of venlafaxine clinical and economic
      evidence.
AB  - Worldwide, major depression is the leading cause of years lived with a
      disability, and the fourth cause of disability-adjusted life years. Depression is
      second only to hypertension as the most common chronic condition encountered in
      general medical practice. Unfortunately, despite the high prevalence of
      depression, under-recognition and under-treatment are common.Historically,
      clinicians have assessed the short-term effectiveness of antidepressants by
      response rates, often defined as a 50% reduction in depressive symptoms. However,
      this usually does not reflect true clinical remission, and residual symptoms are
      common. Persistence of residual symptoms appears to be a common link to relapse,
      chronic disability and suicide. The burden of not treating depression effectively
      to remission is significant, as the disease is an important contributor to the
      disability levels of the general population. Disability, in turn, has a profound
      impact on lost productivity and medical expenses. In 2000, depression cost the US
      more than US 83 billion dollars annually in lost productivity, medical expenses
      and premature death.Venlafaxine, a dual-acting serotonin norepinephrine
      (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment
      and their chances of achieving complete remission compared with conventional
      antidepressant therapies, with the evidence for this being the strongest for
      comparisons with the selective serotonin receptor inhibitors (SSRIs). To date,
      there are only a small number of economic studies of venlafaxine, and most are
      cost or resource utilisation analyses with significant limitations. Nevertheless,
      two cost-effectiveness analyses of venlafaxine are available. They found
      venlafaxine had a lower average cost per patient achieving remission or per
      symptom-free day compared with SSRIs; one reported an incremental cost
      effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per
      additional patient achieving remission over 8 weeks, and the other found
      venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001
      values). Although requiring further confirmation, these initial data suggest that
      venlafaxine is a cost-effective strategy for the treatment of depression. The
      availability of an effective armamentarium of antidepressant strategies,
      including venlafaxine, to achieve and sustain remission offers both clinical and
      economic value to all those touched by the burden of depression.

PMID- 15960554
TI  - Bipolar disorder and health-related quality of life : review of burden of disease
      and clinical trials.
AB  - Bipolar disorder is a chronic psychiatric disorder with a variable course and
      significant impact on patients' social, occupational, and general functioning and
      wellbeing. Although there are effective pharmaceutical and psychosocial
      interventions for patients with bipolar disorder, many patients receive poor
      quality care. Prospective longitudinal studies demonstrate that less than half of
      bipolar disorder patients have a good long-term response to treatment, long-term
      outcome is highly variable, and many patients do not fully recover. There is
      substantial evidence that bipolar disorder is associated with significant
      impairment to functioning and wellbeing.However, few clinical trials comparing
      treatments for bipolar disorder have incorporated health-related quality-of-life
      (HR-QOL) assessments. Existing studies suggest that, while treatment improves HR
      QOL, there is limited evidence for differences between the mood stabilisers in
      terms of HR-QOL outcomes. Additional clinical trials are needed to evaluate
      patient-reported outcomes associated with the most frequently used
      pharmacological treatments to determine whether there are meaningful differences
      between treatments. There are challenges in measuring HR-QOL in patients with
      acute mania, and future studies should assess the psychometric qualities of HR
      QOL instruments in these and other bipolar disorder patients. HR-QOL outcome data
      may be useful in informing psychiatrists, patients and patient family members of
      the effects of treatment for bipolar disorder on patients' everyday lives,
      functioning and wellbeing.

PMID- 15960555
TI  - Pharmacoeconomic evaluation of antidepressants : a critical appraisal of methods.
AB  - In recent years, there has been much debate regarding the real cost effectiveness
      of new antidepressants. This review is an attempt to identify key contentious
      methodological issues that can impact the reliability, validity and quality of
      the research on this subject. There are inherent complexities between inputs and
      outcomes related to depression, and the choice of pharmacoeconomic methodology
      requires a crucial balance between the study design and its ability to capture
      relevant information. Knowledge of the real efficiency of antidepressants should
      always be ascertained with reference to the real-world setting. Studies that show
      a corresponding balance between internal and external validity, coupled with
      sound methodology and standardised reporting, have the potential to translate
      pharmacoeconomics research into real-world, time-relevant decision-making.

PMID- 15960556
TI  - The cost effectiveness of infliximab for severe treatment-resistant rheumatoid
      arthritis in the UK.
AB  - OBJECTIVE: To estimate the cost effectiveness (from the UK NHS and personal
      social service perspectives) of infliximab plus methotrexate (MTX) compared with
      MTX alone, in the treatment of patients with severe rheumatoid arthritis (RA) who
      were not adequately controlled on disease-modifying antirheumatic drugs and who
      were resistant to MTX. METHOD: Clinical data for the first year of therapy were
      taken from the ATTRACT (Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis
      with Concomitant Therapy) and a Markov model developed to assess costs and
      consequences in the longer term. Transition probabilities and health state
      valuations for the model were estimated based on the ARAMIS (Arthritis,
      Rheumatism, and Aging Medical Information System) cohort, and resource use and
      costs ( 2,000 pounds values) obtained from various sources in the UK. Univariate
      sensitivity analyses were conducted to test the robustness of the results.
      RESULTS: The primary analysis suggested that infliximab plus MTX had an ICER of
      33,618 pounds per QALY gained. Alternative modelling assumptions and various
      other sensitivity analyses were applied, but the ICER always remained within the
      range for interventions typically funded by the NHS. CONCLUSION: This model
      suggests, with its underlying assumptions and data, that the combination of
      infliximab and MTX may be a cost-effective treatment (from the UK NHS and
      personal social service perspectives) for patients experiencing RA that cannot be
      maintained on MTX alone.

PMID- 15960557
TI  - Development of an economic model to assess the cost effectiveness of treatment
      interventions for chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To develop a Markov model that allows the cost effectiveness of
      interventions in patients with chronic obstructive pulmonary disease (COPD) to be
      estimated, and to apply the model to investigate the cost effectiveness of an
      inhaled corticosteroid/long-acting beta(2)-adrenoceptor agonist (beta(2)-agonist)
      combination (salmeterol/fluticasone propionate) versus usual care. METHODS: A
      Markov model consisting of four mutually exclusive disease states was constructed
      (mild, moderate and severe disease, and death). The transition probabilities of
      disease progression (for smokers and ex-smokers) and death were derived from the
      published medical literature. The model outputs were costs, exacerbations,
      survival, QALYs and cost effectiveness. The model was made fully probabilistic to
      reflect the joint uncertainty in the model parameters. Efficacy data for the
      combination of inhaled salmeterol/fluticasone propionate 50/500microg twice daily
      in poorly reversible COPD patients with a history of exacerbations were obtained
      from the 1-year TRISTAN (TRial of Inhaled STeroids ANd long-acting beta-agonists)
      study and applied to the model, based on patient profiles representative of COPD
      clinical trials. RESULTS: According to the model, the mean life expectancy with
      usual care alone (placebo group) was 8.95 years, which decreased to 4.08 QALYs
      once adjusted for quality and discounted, at a lifetime discounted cost of Can
      16,415 dollars per patient (year 2002 values). Assuming that
      salmeterol/fluticasone propionate reduced exacerbation frequency only (base case
      analysis), the estimated mean survival time remained unchanged but there was an
      increase in the number of QALYs (4.21) for an estimated lifetime cost of Can
      25,780 dollars, resulting in a cost-effectiveness ratio of Can 74,887 dollars per
      QALY (95% CI 21,985, 128,671) versus usual care. If a survival benefit was
      assumed for salmeterol/fluticasone propionate, the incremental cost per QALY was
      Can11,125 dollars (95% CI 8710, dominated) versus usual care. If the combination
      achieved around a 10% improvement in forced expiratory volume in 1 second,
      leading to delayed progression to more severe disease states, the benefits
      translated into an incremental cost per QALY of Can 49,928 dollars (95% CI 37
      269, 66,006) versus usual care. CONCLUSIONS: This Markov model allows, for the
      first time, a means of estimating the long-term cost effectiveness and cost
      utility of interventions for COPD. Initial evidence suggests that for patients
      with poorly reversible COPD and a documented history of frequent COPD
      exacerbations, the addition of salmeterol (a long-acting beta(2)-agonist) to
      fluticasone propionate (an inhaled corticosteroid) is potentially cost effective
      from the Canadian healthcare payer's perspective. However, the precision of this
      estimate will be improved when additional data are available from clinical trials
      such as the ongoing TORCH (TOwards a Revolution in COPD Health) study.

PMID- 15960558
TI  - Remission rates with 3 consecutive antidepressant trials: effectiveness for
      depressed outpatients.
AB  - OBJECTIVE: This effectiveness study assessed remission rates in patients who had
      the opportunity to receive up to 3 antidepressant trials if unresponsive. METHOD:
      One hundred seventy-one consecutive outpatients entered 1 of 3 studies for the
      treatment of major depressive disorder (DSM-IV criteria) from January 1999
      through December 2001. This group primarily received fluoxetine as a first
      treatment in trials lasting 6 to 12 weeks (a small number received gepirone). If
      unimproved, patients received a second or third trial (primarily clinician's
      choice). A standard criterion to determine remission-a score of 7 or less on the
      17-item Hamilton Rating Scale for Depression-was used. In order to contrast
      remission rates with first-generation antidepressants, patients' outcomes in a
      previously published study that compared placebo, phenelzine, and imipramine were
      also examined (N = 420). RESULTS: In an intent-to-treat analysis, 66% (113/171)
      of patients who were treated with second-generation antidepressants and 65%
      (275/420) of patients who were treated with first-generation antidepressants
      eventually achieved remission. CONCLUSIONS: Remission rates in the effectiveness
      study are approximately 20% higher than the rates usually cited, a result of our
      choice to examine outcome following 3 treatment trials. This choice is dictated
      by good clinical practice. The usual procedure when comparing treatment
      modalities is to assess outcome after a single anti-depressant trial. The
      cumulative high remission rates suggest antidepressants are effective and should
      encourage more patients to seek treatment and physicians to develop techniques to
      improve patient adherence.

PMID- 15960559
TI  - Prevalence, correlates, and comorbidity of DSM-IV antisocial personality
      syndromes and alcohol and specific drug use disorders in the United States:
      results from the national epidemiologic survey on alcohol and related conditions.
AB  - OBJECTIVE: The purpose of this study was to provide nationally representative
      data on the prevalence, sociodemographic correlates, and comorbidity of
      antisocial syndromes across alcohol and 8 specific drug use disorders, including
      sedative, tranquilizer, opiate, stimulant, hallucinogen, cannabis, cocaine, and
      inhalant/solvent abuse and dependence. METHOD: This study is based on a
      nationally representative sample of adults. Lifetime prevalences of antisocial
      syndromes were estimated and logistic regression analyses were used to examine
      associations between antisocial syndromes and sociodemographic characteristics
      and substance use disorders. Diagnoses were made according to the criteria of the
      DSM-IV using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use
      Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. RESULTS:
      The lifetime prevalences of antisocial personality disorder (APD), conduct
      disorder, and adult antisocial behavior were 3.6%, 1.1%, and 12.3%, respectively.
      Prevalences of alcohol use disorders and drug use disorders were 30.3% and 10.3%,
      respectively. In general, men and individuals who were younger,
      widowed/separated/divorced, of lower socioeconomic status, and living in urban
      areas or in the West were more likely to have antisocial syndromes. Native
      Americans were more likely and Asians and Hispanics were less likely to have APD
      and adult antisocial behavior. Virtually all of the associations between APD and
      adult antisocial behavior and specific substance use disorders were positive and
      statistically significant (p < .05). Significant associations between conduct
      disorder and substance use disorders were concentrated among women. CONCLUSION:
      Comorbidity of specific substance disorders with antisocial syndromes is very
      common in the U.S. population. Further work in many directions is indicated by
      the results of this study, including the factors that give rise to the
      associations and the treatment and prevention implications of these conditions
      when comorbid.

PMID- 15960561
TI  - Suicide and attempted suicide in bipolar disorder: a systematic review of risk
      factors.
AB  - OBJECTIVE: To determine the main risk factors for suicide and nonfatal suicidal
      behavior in patients with bipolar disorder through a systematic review of the
      international literature. DATA SOURCES: Studies were identified through
      electronic searches of MEDLINE (1966-December 2003), EMBASE (1980-December 2003),
      PsycINFO (1872-November 2003), and Biological Abstracts (1985-December 2003)
      using index and free-text search terms for bipolar disorder, bipolar depression,
      manic depression, mania, and affective disorders; combined with terms for self
      harm, self-injury, suicide, attempted suicide, automutilation, self-mutilation,
      self-poisoning, and self-cutting; and combined with terms for risk, case control,
      cohort, comparative, longitudinal, and follow-up studies. No language
      restrictions were applied to the search. STUDY SELECTION: Included studies were
      cohort, case-control, and cross-sectional investigations of patients with bipolar
      disorder in which suicide (13 studies) or attempted suicide (23 studies) was
      reported as an outcome. The selected studies also used diagnostic tools including
      the DSM, International Classification of Diseases, and Research Diagnostic
      Criteria. DATA SYNTHESIS: Meta-analysis of factors reported in more than 1 study
      identified the main risk factors for suicide as a previous suicide attempt and
      hopelessness. The main risk factors for nonfatal suicidal behavior included
      family history of suicide, early onset of bipolar disorder, extent of depressive
      symptoms, increasing severity of affective episodes, the presence of mixed
      affective states, rapid cycling, comorbid Axis I disorders, and abuse of alcohol
      or drugs. CONCLUSIONS: Prevention of suicidal behavior in patients with bipolar
      disorder should include attention to these risk factors in assessment and
      treatment, including when deciding whether to initiate treatment aimed
      specifically at reducing suicide risk.

PMID- 15960560
TI  - Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled
      trials of duloxetine for major depressive disorder.
AB  - OBJECTIVE: The onset or worsening of sexual dysfunction is a common treatment
      emergent side effect of antidepressant medications. Post hoc analyses of pooled
      data from placebo-controlled studies were utilized to assess sexual functioning
      in patients receiving duloxetine or paroxetine. METHOD: Acute-phase data were
      obtained from four 8-week, double-blind, placebo- and paroxetine-controlled
      trials of similar design in which patients meeting DSM-IV criteria for major
      depressive disorder were randomly assigned to receive placebo (N = 371),
      duloxetine (40-120 mg/day; N = 736), or paroxetine (20 mg/day; N = 359). Pooling
      of data from these studies was anticipated during study design. This represented
      all available data from duloxetine studies in which the Arizona Sexual Experience
      Scale (ASEX) was administered both at baseline and endpoint. Long-term data were
      available from extension phases in 2 of these trials in which acute treatment
      responders received placebo (N = 129), duloxetine (80-120 mg/day; N = 297), or
      paroxetine (20 mg/day; N = 140) for an additional 26 weeks. Data were collected
      between March 2000 and July 2002. RESULTS: The incidence of acute treatment
      emergent sexual dysfunction was significantly lower among duloxetine-treated
      patients compared with those receiving paroxetine (p = .015), although both rates
      were significantly higher than placebo (p = .007 and p < .001 for duloxetine and
      paroxetine, respectively). Treatment group differences in the incidence of
      treatment-emergent dysfunction did not vary significantly by gender. In female
      patients, acute treatment-emergent sexual dysfunction was significantly lower in
      the duloxetine treatment group compared with the paroxetine treatment group (p =
      .032), with both rates being significantly higher than placebo (p = .049 and p <
      .001 for duloxetine and paroxetine, respectively). In the somewhat smaller group
      of male patients, acute treatment-emergent dysfunction did not differ
      significantly between duloxetine and placebo treatment groups, but the incidence
      was significantly higher in paroxetine-treated male patients compared with male
      placebo patients (p = .012). The long-term incidence of treatment-emergent
      dysfunction did not differ significantly between duloxetine-, paroxetine-, and
      placebo-treated patients. CONCLUSION: In this analysis of pooled data, patients
      receiving duloxetine (40-120 mg/day) or paroxetine (20 mg/day) had a
      significantly higher incidence of acute treatment-emergent sexual dysfunction
      when compared with placebo patients. However, the incidence of acute treatment
      emergent dysfunction for duloxetine was significantly lower than that observed
      for paroxetine.

PMID- 15960562
TI  - Dual reuptake inhibitors incur lower rates of tachyphylaxis than selective
      serotonin reuptake inhibitors: a retrospective study.
AB  - BACKGROUND: The notion that selective serotonin reuptake inhibitors (SSRIs) may
      be associated with higher relapse rates than other antidepressants during
      maintenance treatment (tachyphylaxis) has been discussed for years, but to date
      there is little or no empirical evidence confirming this phenomenon. In this
      study, we systematically assessed prior anti-depressant treatment history in a
      cohort of depressed patients who presented for outpatient psychiatric treatment.
      Rates of tachyphylaxis were compared in venlafaxine and tricyclic antidepressants
      (TCAs), which act as dual reuptake inhibitors, versus SSRIs. METHOD: 237 patients
      who presented for treatment at the Rhode Island Hospital Department of
      Psychiatry's outpatient practice and were diagnosed with DSM-IV major depressive
      disorder were interviewed with the semistructured Treatment Response to
      Antidepressant Questionnaire. This cohort reported having undergone 326 prior
      SSRI trials, 47 prior venlafaxine trials, and 35 prior trials with a TCA. Rates
      of tachyphylaxis as a function of antidepressant class were compared. RESULTS:
      Rates of tachyphylaxis were significantly lower (chi(2) = 6.77, df = 1, p = .01)
      with the dual reuptake inhibitors venlafaxine and TCAs (3 [3.7%] of 82) compared
      to rates of tachyphylaxis with SSRIs (46 [14.1%] of 326). CONCLUSION: These
      results provide preliminary evidence that dual reuptake inhibitors may incur
      lower rates of tachyphylaxis than SSRIs. By virtue of the retrospective and non
      random design of the study, these results warrant confirmation.

PMID- 15960563
TI  - Double-blind comparison of sertraline and placebo in stroke patients with minor
      depression and less severe major depression.
AB  - BACKGROUND: Poststroke depression is a frequent condition and important to treat.
      The aim of this trial was to study the efficacy and tolerability of sertraline.
      METHOD: In 4 Swedish stroke centers, 123 patients (aged 70.7 +/- 9.9 years) were
      enrolled during the period September 1998 to January 2001 in a randomized, double
      blind, placebo-controlled 26-week trial, at a mean of 128 +/- 97 days (range, 3
      375 days) after stroke, if they fulfilled DSM-IV criteria of major depressive
      episode (N = 76) or minor depressive disorder (N = 47). The primary efficacy
      variable was a change in depression assessed by the Montgomery-Asberg Depression
      Rating Scale. The Emotional Distress Scale (EDS) was administered and the
      occurrence of emotionalism and quality of life (QoL) were assessed, as well as
      neurologic recovery. Efficacy analyses were intention-to-treat, short-term (week
      6) and long-term (week 26). RESULTS: Of the 123 patients, 62 were treated with
      sertraline (50-100 mg/day) and 61 with placebo. Both groups improved
      substantially, with no differences between the treatments, either for major
      depressive episode or minor depressive disorder, or for short- or long-term
      antidepressant effect and neurologic outcome. EDS revealed a better outcome with
      sertraline at week 6 (p < .05). At week 26, the improvement in QoL was better in
      sertraline patients (p < .05) and there was a trend for emotionalism (p = .07).
      No serious side effects were seen. CONCLUSION: Poststroke depression as measured
      by a conventional depression rating scale improved over time irrespective of
      treatment. Positive effects specific to sertraline were identified in emotional
      distress, emotionalism, and QoL. The study indicates that poststroke emotional
      reactions comprise depression and other domains susceptible to pharmacologic
      therapy.

PMID- 15960564
TI  - Suicidal ideation and suicide attempts in body dysmorphic disorder.
AB  - OBJECTIVE: Because suicidality in body dys-morphic disorder (BDD) has received
      little investigation, this study examined rates, correlates, predictors, and
      other aspects of suicidal ideation and suicide attempts in this disorder. METHOD:
      From January 2001 to June 2003, 200 subjects with DSM-IV BDD recruited from
      diverse sources were assessed with standard measures. RESULTS: Subjects had high
      rates of lifetime suicidal ideation (78.0%) and suicide attempts (27.5%). Body
      dysmorphic disorder was the primary reason for suicidal ideation in 70.5% of
      those with a history of ideation and nearly half of subjects with a past attempt.
      Suicidal subjects often did not reveal their BDD symptoms to their clinician. In
      univariate analyses, both suicidal ideation and suicide attempts were associated
      with lifetime functional impairment due to BDD (p < .001), current functional
      impairment (p < .001 to < .05), lifetime bipolar disorder (p < .05), any
      personality disorder (p < .05 to .001), and comorbid borderline personality
      disorder (p < .01 to < .001). A history of suicidal ideation (but not suicide
      attempts) was additionally associated with comorbid lifetime major depression (p
      = .001). A history of suicide attempts (but not suicidal ideation) was
      additionally associated with delusional appearance beliefs (p = .01) and lifetime
      posttraumatic stress disorder (PTSD), an eating disorder, or a substance use
      disorder (p < .001 to < .05). In logistic regression analyses, suicidal ideation
      was significantly predicted by comorbid major depression (p = .010) and greater
      lifetime impairment due to BDD (p = .003); suicide attempts were significantly
      predicted by PTSD (p = .011), a substance use disorder (p = .011), and greater
      lifetime impairment due to BDD (p = .005). CONCLUSION: Individuals with BDD have
      high rates of suicidal ideation and suicide attempts. Lifetime impairment due to
      BDD and certain comorbid disorders are associated with suicidality.

PMID- 15960565
TI  - Omega-3 eicosapentaenoic acid in bipolar depression: report of a small open-label
      study.
AB  - INTRODUCTION: Epidemiologic studies have suggested that consumption of cold water
      fish oils may have some protective function against depression. This proposition
      is supported by a series of biochemical and pharmacologic studies that have
      suggested that fatty acids may modulate neurotransmitter metabolism and cell
      signal trans-duction in humans and that abnormalities in fatty acid and
      eicosanoid metabolism may play a causal role in depression. Aware of the critical
      need for antidepression treatments that might not carry the risk of precipitating
      a manic episode in bipolar patients, we decided to conduct an open-label add-on
      trial of eicosapentaenoic acid (EPA) in bipolar depression. METHOD: Twelve
      bipolar I outpatients with depressive symptoms diagnosed by DSM-IV were treated
      with 1.5 to 2 g/day of the omega-3 fatty acid EPA for up to 6 months. The study
      was conducted between September 2001 and January 2003. RESULTS: Eight of the 10
      patients who completed at least 1 month of follow-up achieved a 50% or greater
      reduction in Hamilton Rating Scale for Depression scores within 1 month. No
      patients developed hypomania or manic symptoms. No significant side effects were
      reported. LIMITATIONS: This study is limited both by the open-label design and by
      the small sample size. As in all previous reported studies, patients in this
      study were treated in an outpatient setting, so that the most severely depressed
      bipolar patients (requiring hospitalization) are not represented. CONCLUSIONS:
      Although the ultimate utility of omega-3 fatty acids in bipolar depression is
      still an open question, we believe that these initial results are encouraging,
      especially for mild to moderate bipolar depression, and justify the continuing
      exploration of its use.

PMID- 15960566
TI  - Does recovery from substance use disorder matter in patients with bipolar
      disorder?
AB  - OBJECTIVE: To examine the potential impact of recovery from substance use
      disorder (SUD) on the course of bipolar disorder among patients diagnosed with
      both bipolar and substance use disorders according to DSM-IV criteria. METHOD: As
      part of the multicenter Systematic Treatment Enhancement Program for Bipolar
      Disorder (STEP-BD), we examined bipolar disorder status (i.e., whether the
      patient is recovering or recovered), role functioning, and quality of life in the
      first 1000 patients to enter the STEP-BD study. We compared patients with no
      history of SUD, current SUD, and past SUD (i.e., lifetime SUD, but no current
      SUD) on these parameters. Data were collected between November 1999 and April
      2001. RESULTS: A current clinical status of recovering or recovered from bipolar
      disorder was less likely among patients with current or past SUD compared to
      patients with no SUD (p < .002). Recovering/recovered status did not differ
      significantly between patients with current SUD versus past SUD. All 3 groups
      differed significantly on measures of role functioning as assessed by the
      Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool
      (LIFE-RIFT), with poorest role functioning among patients with current SUD,
      followed by patients with past SUD (p = .0002). Patients with current or past SUD
      reported significantly lower quality of life as measured by the LIFE-RIFT and the
      Quality of Life Enjoyment and Satisfaction Questionnaire and more lifetime
      suicide attempts (p < .001) than patients without an SUD; patients with past
      versus current SUD did not differ significantly on these measures. CONCLUSION:
      The results suggest that patients with bipolar disorder who experience sustained
      remission from an SUD fare better than patients with current SUD, but not as well
      as subjects with no history of SUD; differences among the 3 groups appear
      greatest in the area of role functioning.

PMID- 15960567
TI  - Risperidone and haloperidol augmentation of serotonin reuptake inhibitors in
      refractory obsessive-compulsive disorder: a crossover study.
AB  - BACKGROUND: Although serotonin reuptake inhibitors (SRIs) are the first-line
      treatment for obsessive-compulsive disorder (OCD), approximately half of patients
      with OCD do not respond adequately to SRI monotherapy. Patients with predominant
      obsessions are common in OCD and are often difficult to treat, necessitating
      adjunctive treatment. METHOD: This was a 9-week, double-blind, placebo
      controlled, crossover study comparing the benefits of 2-week adjunctive
      treatments with risperidone, haloperidol, and placebo in patients with OCD (DSM
      IV criteria) who continued to have severe symptoms despite taking a stable dose
      of an SRI. Eligible patients must have been receiving a therapeutic dose of an
      SRI for at least 12 weeks and at the screening visit had a score > or = 10 on
      items 1-5 (obsession) and a total score > or = 16 on the Yale-Brown Obsessive
      Compulsive Scale (YBOCS). Data were collected from January 1999 through April
      2002. RESULTS: Sixteen patients were enrolled and 12 completed the study. On the
      YBOCS, both risperidone and haloperidol significantly reduced obsession (p < .05)
      when compared with placebo. There was a tendency that haloperidol, and to a
      lesser degree risperidone, also reduced the compulsion and the total YBOCS
      scores. These results were accompanied by a reduction in the Hopkins Symptom
      Checklist 90-revised (SCL-90R) anxiety scale score. According to the 17-item
      Hamilton Rating Scale for Depression, the SCL-90R depression scale, and the
      Profile of Mood States, risperidone, but not halo-peridol, also improved
      depressed mood. Neither risperidone nor haloperidol changed neurocogni-tive
      function during the 2-week treatment. All 12 patients completed the 2-week
      risperidone treatment, but 5 of the 12 terminated haloperidol treatment early
      owing to intolerable side effects. CONCLUSION: Adjunctive risperidone improved
      obsessions and depressed mood and was well tolerated in patients with SRI
      refractory OCD.

PMID- 15960568
TI  - An 11- to 13-year follow-up of 75 subjects with obsessive-compulsive disorder.
AB  - OBJECTIVE: There is a paucity of data on the long-term course and outcome of
      obsessive-compulsive disorder (OCD). Available data suggest that OCD runs a
      chronic course with waxing and waning severity. However, most previous studies
      included severely ill patients who were often clinically referred and
      hospitalized. The present study reports the course and outcome of OCD in patients
      who were largely outpatient, self-referred, and drug-naive. METHOD: Seventy-five
      of the 105 subjects (71%) with DSM-IV-diagnosed OCD were followed up 11 to 13
      years after initial consultation in 1991 and 1992 at a major psychiatric hospital
      in India. A majority were self-referred (N = 63, 84%), drug-naive (N = 54, 72%),
      and outpatients (N = 60, 80%). The follow-up evaluations were carried out by
      experienced clinicians using various scales and structured instruments. The
      course and outcome were determined according to predefined criteria. Multinomial
      logistic regression analysis was performed to identify potential predictors of
      outcome. RESULTS: A majority of subjects were adequately treated with medications
      (N = 57, 76%). Out of 75 subjects, only 18 subjects (24%) had clinical OCD.
      Overall, 57 subjects (76%) had a favorable outcome: 32 subjects (43%) had no OCD
      and 25 (33%) had subclinical OCD. Mixed OCD and any Axis I lifetime comorbidity
      predicted "clinical OCD" outcome. CONCLUSIONS: Outcome of OCD is better than
      generally assumed, and the findings of this study offer a new perspective on the
      long-term outcome of OCD. Poor outcome in previous studies may have been due to
      the inclusion of severely and chronically ill patients.

PMID- 15960569
TI  - Antidepressant drug consumption and public health indicators in Italy, 1955 to
      2000.
AB  - OBJECTIVE: This study investigated the impact of the increasing consumption of
      selective serotonin reuptake inhibitors (SSRIs) and newer anti-depressants on the
      following public health indicators: (1) suicide rates, (2) proportion of
      completed suicides by poisoning with solid or liquid substances, and (3) hospital
      admissions for depression and proportion of admissions for depression that were
      first admissions. METHOD: Data collected by IMS Health on antidepressants
      dispensed in Italy from 1983 to 2000 were obtained from the Italian Ministry of
      Health, while data on suicide deaths from 1955 to 2000 were obtained from the
      Italian National Institute of Statistics. RESULTS: In Italy from 1983 to 2000,
      the use of tricyclic antidepressants remained substantially stable, and the use
      of SSRIs and newer agents dramatically increased. In contrast, suicide rates for
      males decreased from 1955 to 1974 and subsequently increased, reaching a peak in
      1985 and then declining. In females, suicide rates remained substantially stable
      until 1978. A subsequent increase occurred up to 1985, followed by a steady
      decline. Suicide by poisoning using solids or liquids dropped by nearly 50% from
      1986 to 2000. Admissions to the hospital for depression showed an erratic
      pattern; however, no decline was observed. No change was observed in the rate of
      first admissions for depression. CONCLUSION: Despite a reduction in suicides by
      poisoning using solids or liquids, the analysis of long-term trends in suicide
      did not suggest that increases in antidepressant prescribing lie behind recent
      reductions in population suicides. Furthermore, in Italy, newer antidepressants
      had no impact on the total number of admissions for depression or on the
      proportion of all admissions that were first admissions.

PMID- 15960570
TI  - Switching outpatients with bipolar or schizoaffective disorders and substance
      abuse from their current antipsychotic to aripiprazole.
AB  - OBJECTIVE: Substance abuse is extremely common in patients with bipolar
      disorders, although minimal data are available on the treatment of this important
      clinical population. Aripiprazole is an atypical antipsychotic that is approved
      for the treatment of mania and that has a novel mechanism of action, acting as a
      dopamine-2 receptor partial agonist, thereby increasing dopamine release in some
      parts of the brain and decreasing dopa-mine release in other brain regions.
      Dopamine release is implicated in substance use, and both dopaminergic agonists
      and antagonists have been examined for the treatment of substance abuse. To our
      knowledge, dopa-mine receptor partial agonists have not been investigated for
      treatment of substance abuse in humans. METHOD: Twenty antipsychotic-treated
      patients with bipolar or schizoaffective disorder and current substance abuse
      were switched to open-label aripipra-zole using an overlap and taper method. At
      baseline, diagnoses were confirmed using the Mini-International Neuropsychiatric
      Interview based on DSM-IV criteria. Psychiatric symptoms, side effects, and
      substance use and craving were assessed over 12 weeks. Psychiatric symptoms were
      assessed with the Hamilton Rating Scale for Depression (HAM-D), Young Mania
      Rating Scale (YMRS), and Brief Psychiatric Rating Scale (BPRS). Substance craving
      was assessed with visual analogue scales, and side effects were monitored using
      the Abnormal Involuntary Movement Scale, Simpson-Angus Scale, Barnes Akathisia
      Scale, and patient report. Study enrollment was from April 2003 to February 2004.
      RESULTS: Significant baseline-to-exit improvement in HAM-D (p = .002), YMRS (p =
      .021), and BPRS (p = .000) scores were observed without a significant change in
      antipsychotic-induced side effect scales. In 17 participants with current alcohol
      dependence, significant reductions in dollars spent on alcohol (p = .042) and
      alcohol craving (p = .003) were found. In 9 participants with cocaine-related
      disorders, significant reductions in cocaine craving (p = .014), but not use,
      were found. CONCLUSION: A change to aripiprazole was associated with symptomatic
      improvement. Limitations of the study include a small sample size, high
      attrition, and an open-label design. Controlled trials in dual-diagnosis patients
      are needed to confirm these findings.

PMID- 15960571
TI  - Differences in prolactin elevation and related symptoms of atypical
      antipsychotics in schizophrenic patients.
AB  - OBJECTIVE: The aim of this cross-sectional study was to investigate the degree
      and frequency of prolactin (PRL) elevation and related symptoms in patients
      treated with 3 different atypical antipsychotics: clozapine, olanzapine, and
      risperidone. METHOD: Twenty-eight patients receiving clozapine, 29 patients
      receiving olanzapine, and 18 patients receiving risperidone (all meeting DSM-IV
      criteria for schizophrenia, schizophreni-form disorder, or schizoaffective
      disorder) were studied. The median daily dose was 400 mg of clozapine, 10 mg of
      olanzapine, and 3 mg of risperidone. Fasting morning blood samples were analyzed
      for PRL, and the occurrence of hyper-prolactinemic symptoms in the patients was
      evaluated. RESULTS: Elevated PRL levels were found in 16 (89%) of the patients
      receiving risperidone and in 7 (24%) of the patients receiving olanzapine, but in
      none of the patients receiving clozapine. In addition, there was a significant
      difference in median PRL level among the treatment groups (p < .0001), in that
      the PRL level was higher both in the patients treated with risperidone and in the
      patients treated with olanzapine, compared to those treated with clozapine.
      Moreover, hyperpro-lactinemic symptoms-menstrual disturbances, galactorrhea,
      impotence, oligospermia, and decreased libido-were reported in 8 (44%) of the
      risperidone-treated patients and in 1 (3%) of the olanzapine-treated patients,
      but in none of the clozapine-treated patients. CONCLUSION: Treatment with
      risperidone was frequently associated with hyperprolactinemia and related
      symptoms, whereas the occurrence of PRL elevation and related symptoms was modest
      in patients receiving olanzapine and nonexistent in those receiving clozapine.
      Thus, atypical anti-psychotics in therapeutic doses differ with regard to effect
      on PRL secretion.

PMID- 15960572
TI  - Empowering women to collaborate in their mental health care.

PMID- 15960573
TI  - A preliminary study of luteal phase versus symptom-onset dosing with escitalopram
      for premenstrual dysphoric disorder.
AB  - OBJECTIVE: This preliminary study compared the efficacy and tolerability of
      escitalopram administered at symptom onset or throughout the luteal phase in
      premenstrual dysphoric disorder (PMDD). METHOD: Twenty-seven women meeting DSM-IV
      criteria for PMDD were randomly assigned in a double-blind manner to luteal phase
      (N = 13) or symptom-onset (N = 14) dosing of escitalopram (10-20 mg/day) for 3
      consecutive menstrual cycles. Participants were enrolled from November 2002 to
      July 2003, and data collection was completed in December 2003. Symptoms were
      assessed using the 17-item Penn Daily Symptom Report (DSR), the Clinical Global
      Impressions-Improvement scale, the Hamilton Rating Scale for Depression, and the
      Sheehan Disability Scale. Scores were compared using repeated measures analysis
      of covariance and t statistics. RESULTS: Luteal phase and symptom-onset groups
      received escitalopram for a mean of 13.5 and 6.0 days, respectively (mean +/- SD
      dose = 15.2 +/- 5.1 mg/day at the third treatment cycle). Total premenstrual DSR
      scores significantly improved from baseline (p = .003), with a 57% decrease in
      the luteal phase group and a 51% decrease in the symptom-onset group. Clinical
      improvement (DSR score decrease > or = 50% from baseline) was reported by 11 of
      13 patients in the luteal phase group and 9 of 14 patients in the symptom-onset
      group. Symptom severity differentiated the response in the symptom-onset group,
      with those having more severe symptoms less likely to respond. Symptom severity
      did not differentiate treatment response to luteal phase dosing. Escitalopram was
      well tolerated. Adverse events were mild and transient, with only 2 patients
      discontinuing due to adverse events related to the medication. CONCLUSION:
      Premenstrual dysphoric disorder improved significantly with either luteal phase
      or symptom-onset dosing of escitalopram. Women with more severe PMDD may respond
      better to luteal phase dosing than symptom-onset dosing.

PMID- 15960574
TI  - Estrogen augmentation of antidepressants in perimenopausal depression: a pilot
      study.
AB  - OBJECTIVE: To investigate the effects of estrogen augmentation on mood and memory
      in women with perimenopausal depression who had experienced a partial response to
      antidepressant medications. METHOD: In a double-blind, placebo-controlled trial,
      17 subjects taking antidepressant medication were randomly assigned to either
      0.625 mg/day of conjugated estrogen (N = 11) or matching placebo (N = 6) for 6
      weeks. Women between the ages of 40 and 60 years with DSM-IV major depressive
      disorder (MDD) in partial remission who had been taking antidepressant medication
      for a minimum of 8 weeks and were experiencing 1 or more perimenopausal symptoms
      (hot flashes, night sweats, irregular periods, sleep disturbance, memory
      impairment) were recruited from the community. The primary outcome measures were
      the final scores for the Hamilton Rating Scale for Depression (HAM-D) and the
      Buschke Selective Reminding Test. Data were gathered from April 2002 to August
      2003. RESULTS: Women receiving estrogen had a significantly larger decrease in
      HAM-D scores than women receiving placebo (t = 2.86, df = 15, p = .012). Group
      differences in tests of verbal memory were not significant, although improved
      scores in verbal memory were significantly correlated with a decrease in follicle
      stimulating hormone (p = .021). CONCLUSION: Short-term, low-dose estrogen
      augmentation of antidepressant medication was significantly associated with
      improved mood, but not memory, in perimenopausal women with MDD in partial
      remission.

PMID- 15960575
TI  - Prevalence and predictors of parenting outcomes in a cohort of mothers with
      schizophrenia admitted for joint mother and baby psychiatric care in England.
AB  - OBJECTIVES: Most women with schizophrenia have children. Schizophrenia has been
      identified as an independent predictor of poor parenting outcome following joint
      mother and baby psychiatric admission. We aimed to describe the characteristics
      of these women postnatally and to estimate the prevalence of, and identify
      independent predictors of, parenting outcomes. METHOD: Clinical and psychosocial
      data from consecutive joint psychiatric admissions of mothers and infants between
      September 1996 and September 2002 were collected. Diagnoses were based on ICD-10
      criteria (N = 239 schizophrenia; N = 693 affective disorders). The prevalence of
      each parenting outcome at discharge, assessed according to social services
      intervention and staff-rated measures of parenting ability, was estimated.
      Factors associated with poor parenting outcomes and independent predictors were
      identified using "modified" Poisson regression, and prevalence of these parenting
      outcomes was estimated in subgroups of mothers stratified by combinations of
      protective/risk factors. RESULTS: Mothers with schizophrenia were characterized
      as having more complex clinical and psychosocial problems and were considerably
      more likely to experience all types of poor parenting outcomes, compared to
      mothers with affective disorders. Mothers with schizophrenia reporting supportive
      marital and other relationships, those whose partners were well, and those of
      higher social class showed the best parenting outcomes. CONCLUSIONS: Mothers with
      schizophrenia who experience better parenting outcomes may be protected by
      certain factors. Successful parenting is related, partly, to stability within the
      family and access to financial and social resources. The nature of the
      relationship between identified predictors and parenting outcomes in this group
      is unclear but may suggest that parenting outcome varies with clinical outcome in
      schizophrenia. Future research and service development should focus on potential
      protective factors that may encourage successful parenting outcomes in this
      vulnerable group.

PMID- 15960576
TI  - Advancing the treatment of people with mental illness: a call to action in the
      management of metabolic issues.

PMID- 15960577
TI  - Cultural competence in clinical psychopharmacology.

PMID- 15960578
TI  - Monosymptomatic hypochondriacal psychosis: atypical presentation and response to
      olanzapine.

PMID- 15960579
TI  - An African patient with ziprasidone intolerance.

PMID- 15960580
TI  - A case of delirium and subsequent pancytopenia associated with the oral loading
      of valproic acid.

PMID- 15960581
TI  - Issues to consider in the assessment and treatment of paraphilic patients.

PMID- 15960589
TI  - Comparative photobiology of growth responses to two UV-B wavebands and UV-C in
      dim-red-light- and white-light-grown cucumber (Cucumis sativus) seedlings:
      physiological evidence for photoreactivation.
AB  - We examined the influence of short-term exposures of different UV wavebands on
      the elongation and phototropic curvature of hypocotyls of cucumbers (Cucumis
      sativus L.) grown in white light (WL) and dim red light (DRL). We evaluated (1)
      whether different wavebands within the ultraviolet B (UV-B) region elicit
      different responses; (2) the hypocotyl elongation response elicited by
      ultraviolet C (UV-C); (3) whether irradiation with blue light-enriched white
      light (B/WL) given simultaneous with UV-B treatments reversed the effect of UV in
      a manner indicative of photoreactivation; and (4) whether responses in WL-grown
      plants were similar to those grown in DRL. Responses to brief (1-100 min)
      irradiations with three different UV wavebands all induced inhibition of
      elongation measured after 24 h. When WL-grown seedlings were irradiated with
      light containing proportionally greater short wavelength UV-B (37% of UV-B
      between 280 and 300 nm), inhibition of hypocotyl elongation was induced at a
      threshold of 0.5 kJ m(-2), whereas exposure to UV-B including only wavelengths
      longer than 290 nm (and only 8% of UV-B between 290 and 300 nm) induced
      inhibition of hypocotyl elongation at a threshold of 1.6 kJ m(-2). The UV-C
      treatment induced reduction in elongation at a threshold of <0.01 kJ m(-2) for
      DRL-grown plants and <0.03 kJ m(-2) for WL-grown plants. B/WL caused 50% reversal
      of the short-wavelength UV-B-induced inhibition of elongation in DRL-grown
      seedlings but did not reverse the effect of long-wavelength UV-B. B/WL caused 30%
      reversal of the UV-C-induced inhibition of elongation in WL-grown seedlings but
      did not affect the response to short-wavelength UV-B. Short-wavelength UV-B also
      induced positive phototropic curvature in both types of seedlings, and this was
      reversed 60% or completely in DRL-grown and WL-grown seedlings, respectively. The
      similarity of responses between the etiolated (DRL-grown) and de-etiolated (WL
      grown) seedlings indicates that the short-wavelength specific response may be
      relevant to natural light environments, and the apparent photoreactivation
      implicates DNA damage as the sensory mechanism for the response.

PMID- 15960590
TI  - Preclinical evaluation of a novel water-soluble chlorin E6 derivative (BLC 1010)
      as photosensitizer for the closure of the neovessels.
AB  - In the present study, photodynamic activity of a novel photosensitizer (PS),
      Chlorin e(6)-2.5 N-methyl-d-glucamine (BLC 1010), was evaluated using the
      chorioallantoic membrane (CAM) as an in vivo model. After intravenous (i.v.)
      injection of BLC 1010 into the CAM vasculature, the applicability of this drug
      for photodynamic therapy (PDT) was assessed in terms of fluorescence
      pharmacokinetics, i.e. leakage from the CAM vessels, and photothrombic activity.
      The influence of different PDT parameters including drug and light doses on the
      photodynamic activity of BLC 1010 has been investigated. It was found that,
      irrespective of drug dose, an identical continuous decrease in fluorescence
      contrast between the drug inside and outside the blood vessels was observed. The
      optimal treatment conditions leading to desired vascular damage were obtained by
      varying drug and light doses. Indeed, observable damage was achieved when
      irradiation was performed at light doses up to 5 J/cm(2) 1 min after i.v.
      injection of drug doses up to 0.5 mg/kg body weight(b.w.). However, when
      irradiation with light doses of more than 10 J/cm(2) was performed 1 min after
      injection of drug doses up to 2 mg/kg body weight, this led to occlusion of large
      blood vessels. It has been demonstrated that it is possible to obtain the desired
      vascular occlusion and stasis with BLC 1010 for different combinations of drug
      and/or light doses.

PMID- 15960591
TI  - Modeling of a type II photofrin-mediated photodynamic therapy process in a
      heterogeneous tissue phantom.
AB  - We present a quantitative framework to model a Type II photodynamic therapy (PDT)
      process in the time domain in which a set of rate equations are solved to
      describe molecular reactions. Calculation of steady-state light distributions
      using a Monte Carlo method in a heterogeneous tissue phantom model demonstrates
      that the photon density differs significantly in a superficial tumor of only 3 mm
      thickness. The time dependences of the photosensitizer, oxygen and intracellular
      unoxidized receptor concentrations were obtained and monotonic decreases in the
      concentrations of the ground-state photosensitizer and receptor were observed. By
      defining respective decay times, we quantitatively studied the effects of photon
      density, drug dose and oxygen concentration on photobleaching and cytotoxicity of
      a photofrin-mediated PDT process. Comparison of the dependences of the receptor
      decay time on photon density and drug dose at different concentrations of oxygen
      clearly shows an oxygen threshold under which the receptor concentration remains
      constant or PDT exhibits no cytotoxicity. Furthermore, the dependence of the
      photosensitizer and receptor decay times on the drug dose and photon density
      suggests the possibility of PDT improvement by maximizing cytotoxicity in a tumor
      with optimized light and drug doses. We also discuss the utility of this model
      toward the understanding of clinical PDT treatment of chest wall recurrence of
      breast carcinoma.

PMID- 15960592
TI  - Alpha-methylstilbene and the duality of mechanism in the quenching of stilbene
      triplets by molecular oxygen.
AB  - Spin-exchange quenching of alpha-methylstilbene triplets by molecular oxygen and
      by the free radical di-tert-butyl nitroxide is shown to favor the cis isomer more
      than does natural decay. The effect of the two quenching events is an identical
      7% decrease in the fraction of perpendicular triplets that decay to the trans
      isomer. The conclusion that relaxed stilbene triplets reside in a shallow minimum
      corresponding to a geometry in which the two benzyl moieties are orthogonal was
      based on the observation that their quenching by O2 does not alter the trans/cis
      photostationary ratio. Our results with alpha-methylstilbene confirm the
      hypothesis that in the case of stilbene spin exchange quenching by O2 at the
      twisted geometry favors the cis isomer but occurs in competition with excitation
      transfer from transoid triplets that leads to the trans isomer and to singlet
      oxygen. The opposite effects of the two oxygen quenching paths on stilbene isomer
      composition cancel accidentally leading to an overall insensitivity of
      benzophenone-sensitized photostationary states to the presence of oxygen.
      Quenching rate constants derived on the basis of this cancellation are close to
      diffusion-controlled and predict singlet O2 quantum yields of 0.08 and 0.13 in
      the presence of air and under an O2 atmosphere, in good agreement with
      experimental measurements.

PMID- 15960593
TI  - Enzyme-assisted reforming of glucose to hydrogen in a photoelectrochemical cell.
AB  - Hydrogen gas has been produced by reforming glucose in a hybrid
      photoelectrochemical cell that couples a dye-sensitized nanoparticulate wide band
      gap semiconductor photoanode to the enzyme-based oxidation of glucose. A layer of
      porphyrin sensitizer is adsorbed to a TiO2 nanoparticulate aggregate sintered to
      a conducting glass substrate to form the photoanode. Excitation of the porphyrin
      results in electron injection into the TiO2, and migration to a microporous
      platinum cathode where hydrogen is produced by hydrogen ion reduction. The
      oxidized sensitizer dye is reduced by NADH, regenerating the dye and poising the
      NAD+/NADH redox couple oxidizing. The NAD+ is recycled to NADH by the enzyme
      glucose dehydrogenase, which obtains the necessary electrons from oxidation of
      glucose. The reforming of glucose produces gluconolactone, which hydrolyzes to
      gluconate; the electrochemical potential necessary to overcome thermodynamic and
      kinetic barriers to hydrogen production by NADH is provided by light. The quantum
      yield of hydrogen is approximately 2.5%.

PMID- 15960594
TI  - Mechanism of visible light phototoxicity on Porphyromonas gingivalis and
      Fusobacterium nucleatum.
AB  - Phototoxicity of visible light laser on the porphyrin-producing bacteria,
      Porphyromonas gingivalis, in the absence of photosensitizers and under aerobic
      conditions was shown in previous studies. Recently, we found that the noncoherent
      visible light sources at wavelengths of 400-500 nm, commonly used in restorative
      dentistry, induced a phototoxic effect on P. gingivalis, as well as on
      Fusobacterium nucleatum, and to a lesser extent on the Streptococci sp. To
      elucidate the mechanism of this phototoxic effect, P. gingivalis and F. nucleatum
      were exposed to light (1) under aerobic and anaerobic environments and (2) in the
      presence of scavengers of reactive oxygen species (ROS). Phototoxic effect was
      not observed when the bacteria were exposed to light under anaerobic conditions.
      Dimethyl thiourea, a hydroxyl radical scavenger, was effective in reducing
      phototoxicity (P </= 0.05). Other scavengers, such as catalase, superoxide
      dismutase and ascorbic acid, were less effective when applied separately. These
      results support the assumption that the phototoxic effect of blue light on the
      periopathogenic bacteria is oxygen dependent and that hydroxyl radicals play an
      important role in this process.

PMID- 15960595
TI  - Fluorescence spectroscopic study of hypericin-photosensitized oxidation of low
      density lipoproteins.
AB  - By means of UV-VIS absorption and fluorescence spectroscopy, we demonstrate that
      the photosensitizer hypericin (Hyp) interacts nonspecifically with low-density
      lipoproteins (LDL), most probably with the lipid fraction of LDL. The molar ratio
      of monomeric Hyp binding to nonoxidized LDL and mildly oxidized LDL is 30:1.
      Increasing the Hyp concentration further leads to the formation of Hyp aggregates
      inside the LDL molecule. We also demonstrate that photoactivated Hyp oxidizes LDL
      in a light dose and excitation wavelength dependent manner. The level of
      oxidation of LDL depends on the amount of Hyp inside the LDL molecule. The
      maximum of the photosensitized oxidation of the LDL by Hyp is achieved for a 30:1
      molar ratio, which corresponds to the maximum concentration of monomeric form of
      Hyp in LDL.

PMID- 15960596
TI  - Adeno-associated virus-mediated gene transfer for lung diseases.

PMID- 15960597
TI  - Adeno-associated virus-vectored gene therapy for retinal disease.
AB  - Recombinant adeno-associated viral (AAV) vectors have become powerful gene
      delivery tools for the treatment of retinal degeneration in a variety of animal
      models that mimic corresponding human diseases. AAV vectors possess a number of
      features that render them ideally suited for retinal gene therapy, including a
      lack of pathogenicity, minimal immunogenicity, and the ability to transduce
      postmitotic cells in a stable and efficient manner. In the sheltered environment
      of the retina, AAV vectors are able to maintain high levels of transgene
      expression in the retinal pigmented epithelium (RPE), photoreceptors, or ganglion
      cells for long periods of time after a single treatment. Each cell type can be
      specifically targeted by choosing the appropriate combination of AAV serotype,
      promoter, and intraocular injection site. The focus of this review is on examples
      of AAV-mediated gene therapy in those animal models of inherited retinal
      degeneration caused by mutations directly affecting the interacting unit formed
      by photoreceptors and the RPE. In each case discussed, expression of the
      therapeutic gene resulted in significant recovery of retinal structure and/or
      visual function. Because of the key role of the vasculature in maintaining a
      healthy retina, a summary of AAV gene therapy applications in animal models of
      retinal neovascular diseases is also included.

PMID- 15960598
TI  - Evaluation of biodistribution and safety of adenovirus vectors containing group B
      fibers after intravenous injection into baboons.
AB  - Vectors containing group B adenovirus (Ad) fibers are able to efficiently
      transduce gene therapy targets that are refractory to infection with standard Ad
      serotype 5 (Ad5) vectors, including malignant tumor cells, hematopoietic stem
      cells, and dendritic cells. Preliminary studies in mice indicate that, after
      intravenous injection, B-group fiber-containing Ads do not efficiently transduce
      most organs and cause less acute toxicity than Ad5 vectors. However,
      biodistribution and safety studies in mice are of limited value because the mouse
      analog of the B-group Ad receptor, CD46, is expressed only in the testis, whereas
      in humans, CD46 is expressed on all nucleated cells. Unlike mice, baboons have
      CD46 expression patterns and levels that closely mimic those in humans. We
      conducted a biodistribution and toxicity study of group B Ad fiber-containing
      vectors in baboons. Animals received phosphate-buffered saline, Ad5-bGal (a first
      generation Ad5 vector), or B-group fiber-containing Ads (Ad5/35-bGal and Ad5/11
      bGal) at a dose of 2 x 10(12) VP/kg, and vector biodistribution and safety was
      analyzed over 3 days. The amount of Ad5/35-bGal and Ad5/11-bGal vector genomes
      was in most tissues one to three orders of magnitude below that of Ad5.
      Significant Ad5/35- and Ad5/11-mediated transgene (beta-galactosidase) expression
      was seen only in the marginal zone of splenic follicles. Compared with the animal
      that received Ad5-bGal, all animals injected with B-group fiber-containing Ad
      vectors had lower elevations in serum proinflammatory cytokine levels. Gross and
      histopathology were normal in animals that received B-group Ad fiber-containing
      Ads, in contrast to the Ad5-infused animal, which showed widespread endothelial
      damage and inflammation. In a further study, a chimeric Ad5/35 vector carrying
      proapoptotic TRAIL and Ad E1A genes under tumor-specific regulation was well
      tolerated in a 30-day toxicity study. No major clinical, serologic, or pathologic
      abnormalities were noticed in this animal.

PMID- 15960599
TI  - Patterns of gene expression from in utero delivery of adenoviral-associated
      vector serotype 1.
AB  - Adenoviral-associated viral vectors (AAV) have shown significant promise for
      efficient gene delivery to multiple tissues. Studies of different serotypes of
      AAV revealed different expression patterns provided by gene delivery in postnatal
      mice. Previous in utero gene delivery studies of AAV serotype 2 (AAV2)
      demonstrated efficient gene expression in certain fetal tissues depending on
      route of administration. We studied the pattern of gene expression from AAV
      serotype 1 (AAV1) using intramuscular, intraperitoneal, and intravascular routes
      of administration in embryonic day 16 C57BL/6 mice. Limb skeletal muscle
      transduction was only achieved with AAV1 by intramuscular administration. The
      levels of gene expression were 20-fold higher than a comparable administration of
      AAV2. Diaphragm muscle transduction by AAV1 was achieved at the highest level by
      intraperitoneal administration, and to a lesser degree by intravascular
      administration. All delivery routes resulted in transgene expression in the lung.
      Our results indicate that AAV1 can offer higher transgene expression in fetal
      skeletal muscle than AAV2 with intramuscular administration. The transgene
      expression pattern in different tissues, which depends on vector serotype and
      route of administration, will need to be considered in planning therapeutic
      studies for specific disorders.

PMID- 15960601
TI  - Adeno-associated virus 2-mediated intratumoral prostate cancer gene therapy: long
      term maspin expression efficiently suppresses tumor growth.
AB  - Maspin is a member of the serine protease inhibitors and the maspin gene, a tumor
      suppressor gene, is down-regulated in a large fraction of prostate cancers. We
      evaluated the use of adeno-associated virus (AAV, serotype 2) vector encoding
      maspin as a means for in vivo gene therapy for human prostate cancer. TUNEL assay
      of subcutaneously formed LNCaP or DU145 tumors in nude mice showed that
      intratumoral AAV-mediated maspin expression significantly upregulated the number
      of apoptotic cells compared with AAV-LacZ treatment. Immunofluorescence double
      staining for maspin protein and apoptosis in LNCaP tumors showed that the
      percentage of apoptotic cells in AAV-maspin-mediated maspin-expressing cells was
      significantly high compared with that in AAV-GFP-mediated GFP-expressing cells.
      Moreover, significantly fewer CD31-positive microvessels were observed in AAV
      maspin-treated tumors compared with the control tumors. These therapeutic
      responses were highly correlated to persistent maspin expression in tumors,
      confirmed by Western blot analysis until at least day 56 after treatment.
      Finally, intratumoral delivery of AAV-maspin significantly suppressed growth of
      LNCaP and DU145 tumors and improved survival of mice. We conclude that AAV
      mediated prolonged maspin expression efficiently suppresses human prostate tumor
      growth in vivo by apoptosis induction and inhibition of angiogenesis.

PMID- 15960600
TI  - Therapeutic efficacy of PUMA for malignant glioma cells regardless of p53 status.
AB  - Replacement of the p53 tumor suppressor gene is a rational approach to the
      management of malignant gliomas because p53 is frequently mutated or inactivated
      in these cancers. Major weaknesses of this approach are that malignant gliomas
      are mixtures of cells with wild-type and mutant p53, and that tumor cells
      exhibiting wildtype p53 are resistant to p53 gene transfer. An effective
      alternative is needed to overcome these difficulties. p53-upregulated modulator
      of apoptosis (PUMA) was identified as a p53-inducible proapoptotic molecule. Our
      purpose was to elucidate a role for PUMA in p53 gene therapy and to investigate
      whether PUMA is an efficient substitute for p53 in cancer therapy. We
      demonstrated that PUMA was upregulated in mutant p53 malignant glioma cells (U373
      MG and T98G) undergoing apoptosis but was not upregulated in apoptosis-resistant
      wild-type p53 malignant glioma cells (U87-MG and D54) after adenoviral transfer
      of p53. Overexpression of PUMA resulted in massive apoptosis associated with
      mitochondrial damage and caspase-3 activation in all tumor cells tested. Use of
      the human telomerase reverse transcriptase (hTERT) promoter system induced
      apoptosis only in malignant glioma cells with telomerase activity, while sparing
      normal cells lacking telomerase. The ability of PUMA to induce apoptosis was
      greater than that of caspase-6 or caspase-8 transfer, using the same system.
      Moreover, exogenous expression of PUMA under the hTERT promoter system
      significantly suppressed the growth of subcutaneous U87-MG tumors in nude mice
      and did not induce apoptosis in surrounding nontumor tissues. These results
      indicate that PUMA, which is regulated under a tumor-specific expression system
      such as the hTERT promoter, may be better than p53 as a therapeutic tool for
      malignant gliomas.

PMID- 15960602
TI  - Gamma-glutamylcysteine synthetase and L-buthionine-(S,R)-sulfoximine: a new
      selection strategy for gene-transduced neural and hematopoietic stem/progenitor
      cells.
AB  - In most experimental gene therapy protocols involving stem/progenitor cells, only
      a small fraction of cells, often therapeutically inadequate, can be transduced
      and made to express the therapeutic gene. A promising strategy for overcoming
      this problem is the use of a dominant selection marker, such as a drug resistance
      gene. In this paper, we explore the potential of the heavy subunit of gamma
      glutamylcysteine synthetase (gamma-GCSh) to act as a selection marker. We found
      that 3T3 fibroblasts transduced with the bicistronic retroviral vector SF91/GCSh
      eGFP, encoding gamma-GCSh and the enhanced green fluorescent protein (eGFP), were
      highly resistant to L-buthionine-(S,R)-sulfoximine (BSO), a gamma-GCS inhibitor
      with a low clinical toxicity profile. The level of resistance was not
      proportional to the increase in intracellular glutathione. In fact, cells
      overexpressing both heavy and light gamma-GCS subunits had higher intracellular
      GSH levels, and a lower level of resistance to the cytotoxic activity of BSO,
      compared with cells overexpressing gamma-GCSh alone. 3T3 fibroblasts
      overexpressing gamma-GCSh could be selected from cultures containing both naive
      and gene-modified cells by application of exogenous BSO selection pressure for 4
      days. Also, primary neural stem/progenitor cells derived from the lateral
      ventricles of mouse neonatal brains and primary hematopoietic stem/progenitor
      cells (HSCs/HPCs) from mouse bone marrow, transduced with the gamma-GCSh-eGFP
      vector, could be selected by BSO treatment in vitro. On ex vivo BSO selection and
      reimplantation into a syngeneic myeloablated host, donor HSCs/HPCs repopulated
      the marrow and continued to express the transgene(s). These results provide proof
      of principle that somatic stem/progenitor cells, transduced simultaneously with a
      potentially curative gene and gamma-GCSh, can be selected by treatment with BSO
      before in vivo transplantation.

PMID- 15960603
TI  - Cyclosporine inhibits the development of green fluorescent protein (GFP)-specific
      immune responses after transplantation of GFP-expressing hematopoietic
      repopulating cells in dogs.
AB  - Green fluorescent proteins (GFPs) have been widely used to monitor gene transfer
      and expression after lentiviral and oncoretroviral transduction of hematopoietic
      cells. Studies have shown a complete disappearance of GFP-containing cells after
      transplantation of GFP-transduced repopulating cells in nonhuman primates that
      was further shown to be mediated by transgene-specific immune responses. We
      wished to evaluate whether cyclosporine could prevent immune responses to GFP. We
      first determined whether an immune response to GFP was responsible for the
      disappearance of gene-modified cells in dogs. We performed immune assays in two
      dogs transplanted with lentivirally transduced CD34+ cells. Blood samples were
      obtained twice per week for up to 800 days and the GFP transgene product was
      measured by flow cytometry in blood leukocytes. Peripheral blood leukocytes were
      stimulated in vitro for 5 days, using a panel of GFP peptides. Intracellular
      levels of tumor necrosis factor alpha (TNF-alpha), measured by flow cytometry,
      and T cell proliferation after GFP peptide stimulation were measured. Dogs that
      exhibited a decrease in GFP marking developed potent immune responses in vitro to
      the transgene product GFP as shown by an increase in GFP-specific TNF-alpha
      production (p < 0.05) when compared with nontransplanted controls. T cells from
      dogs with low GFP marking exhibited a significant increase in proliferation in
      response to GFP peptide stimulation in vitro (p < 0.05). To study whether
      cyclosporine could inhibit the development of GFP-specific immune responses, we
      treated five dogs with cyclosporine after transplantation of GFP-transduced
      hematopoietic cells. Dogs treated with cyclosporine after hematopoietic stem cell
      transplantation showed stable GFP marking in blood leukocytes over 800 days. Our
      data suggest that cyclosporine prevents immunoactivation against transgene
      products after transplantation of GFP-transduced hematopoietic stem cells as
      indicated by stable GFP marking.

PMID- 15960604
TI  - Vascular oligonucleotide transfer facilitated by a polymer-coated stent.
AB  - To evaluate the potential of clinically used phosphorylcholine (PC)-coated stents
      for their ability to load and release small decoy oligonucleotides (ODNs). Stents
      were loaded with 41 +/- 6 microg ODNs. Ex vivo deployment of ODN-loaded stents in
      explanted rabbit aortas showed significant vascular ODN transfer, with 18 +/- 12%
      of intimal or medial cell nuclei containing ODNs. In proof-of-principle in vivo
      experiments (using the double-injury rabbit model) there was no difference in
      fluorescent signal intensity between animals receiving ODNloaded stents or
      controls. However, a significant increase in signal intensity was detected in the
      kidneys of animals receiving ODN-loaded stents. PC-coated stents can be loaded
      with ODNs. Despite successful ex vivo ODN deposition and nuclear uptake in the
      vessel wall, in vivo vascular ODN transfer was not achieved. Rapid intravascular
      release of ODN before implantation and potential vascular barriers for gene
      transfer are most likely responsible for the currently unsatisfactory in vivo
      release kinetics.

PMID- 15960605
TI  - Stability of lentiviral vector-mediated transgene expression in the brain in the
      presence of systemic antivector immune responses.
AB  - Lentiviral vectors are promising tools for gene therapy in the CNS. It is
      therefore important to characterize their interactions with the immune system in
      the CNS. This work characterizes transgene expression and brain inflammation in
      the presence or absence of immune responses generated after systemic immunization
      with lentiviral vectors. We characterized transduction with SIN-LV vectors in the
      CNS. A dose-response curve using SIN-LV-GFP demonstrated detectable transgene
      expression in the striatum at a dose of 10(2), and maximum expression at 10(6),
      transducing units of lentiviral vector, with minimal increase in inflammatory
      markers between the lowest and highest dose of vector injected. Our studies
      demonstrate that injection of a lentiviral vector into the CNS did not cause a
      measurable inflammatory response. Systemic immunization after CNS injection, with
      the lentiviral vector expressing the same transgene as a vector injected into the
      CNS, caused a decrease in transgene expression in the CNS, concomitantly with an
      infiltration of inflammatory cells into the CNS parenchyma at the injection site.
      However, peripheral immunization with a lentiviral vector carrying a different
      transgene did not diminish transgene expression, or cause CNS inflammation.
      Systemic immunization preceding injection of lentiviral vectors into the CNS
      determined that preexisting antilentiviral immunity, regardless of the transgene,
      did not affect transgene expression. Furthermore, we showed that the transgene,
      but not the virion or vector components, is responsible for providing antigenic
      epitopes to the activated immune system, on systemic immunization with
      lentivirus. Low immunogenicity and prolonged transgene expression in the presence
      of preexisting lentiviral immunity are encouraging data for the future use of
      lentiviral vectors in CNS gene therapy. In summary, the lentiviral vectors tested
      induced undetectable activation of innate immune responses, and stimulation of
      adaptive immune responses against lentiviral vectors was effective in causing a
      decrease in transgene expression only if the immune response was directed against
      the transgene. A systemic immune response against vector components alone did not
      cause brain inflammation, possibly because vector-derived epitopes were not being
      presented in the CNS.

PMID- 15960606
TI  - Interleukin 7-engineered stromal cells: a new approach for hastening naive T cell
      recruitment.
AB  - In this study we determined whether human stromal cells could be engineered with
      a retroviral vector carrying the interleukin 7 (IL-7) gene and investigated the
      effects on T cells in vitro and in vivo in a murine model. Transduced mesenchymal
      cells strongly express CD90 (98.15%), CD105 (87.6%), and STRO-1 (86.7%). IL-7
      production was 16.37 (+/-2 SD) pg/ml, which remained stable for 60 days. In vitro
      immunoselected naive T cells maintained the CD45RA+ CD45RO- naive phenotype (4.2
      times more than controls) after 7 days of culture with IL-7-engineered stromal
      cells. The apoptosis rate (4.7%) of the naive T cells cultured with transduced
      stromal cells overlapped with that of freshly isolated cells. Immunohistological
      analysis detected stromal cells in bone marrow, spleen, and thymus.
      Cotransplantation of IL-7-engineered stromal cells with CD34+ cells improved
      engraftment in terms of CD45+ cells and significantly increased the CD3+ cell
      count in peripheral blood, bone marrow, and spleen. These data demonstrate the
      following: (1) human stromal cells can be transduced, generating a normal layer;
      (2) transduced stromal cells in vitro maintain the naive T cell phenotype; and
      (3) IL-7-transduced stromal cells in vivo home to lymphoid organs and produce
      sufficient IL-7 in loco, supporting T cell development in a cotransplantation
      model. Because of their efficient cytokine production and homing, IL-7-engineered
      stromal cells might be an ideal vehicle to hasten immunological reconstitution in
      T cell-depleted hosts.

PMID- 15960607
TI  - Oncolytic HSV exerts direct antiangiogenic activity in ovarian carcinoma.
AB  - In the present study, we investigated the ability of replication-restricted
      herpes simplex virus (HSV) 1716 lacking ICP34.5 to infect endothelium and disrupt
      tumor vasculature. HSV-1716 efficiently infected and killed mouse endothelial
      cell lines H5V and MS1 cells, as well as human umbilical vein endothelial cells
      in vitro. Capillary tube formation by endothelial cells was inhibited by HSV-1716
      in vitro and in vivo. Following intratumoral administration of oncolytic HSV
      1716, HSV-glycoproteins could be detected in CD31-positive tumor vascular
      endothelium by immunostaining. Viral DNA was recovered from highly purified
      microdissected tumor vascular endothelium. Furthermore, endothelium of tumors
      treated with HSV-1716 exhibited expression of tissue factor, a marker of
      endothelial damage. Importantly, HSV antigen and DNA were also detected in
      endothelium distant from foci of active tumor infection. After intravascular
      inoculation of HSV-1716, viral glycoproteins were detected in association to
      tumor endothelium, but not vascular endothelium of different organs. Purified
      tumor endothelial cells showed high proliferative capability and were susceptible
      to HSV-1716 infection and killing ex vivo while endothelium from normal organs
      was not. We conclude that oncolytic HSV-1716 exerts direct antiangiogenic
      effects, which may contribute to the overall therapeutic efficacy of the virus.

PMID- 15960609
TI  - Mutations in dopachrome tautomerase (Dct) affect eumelanin/pheomelanin synthesis,
      but do not affect intracellular trafficking of the mutant protein.
AB  - Dopachrome tautomerase (Dct) is a type I membrane protein and an important
      regulatory enzyme that plays a pivotal role in the biosynthesis of melanin and in
      the rapid metabolism of its toxic intermediates. Dct-mutant melanocytes carrying
      the slaty or slaty light mutations were derived from the skin of newborn congenic
      C57BL/6J non-agouti black mice and were used to study the effect(s) of these
      mutations on the intracellular trafficking of Dct and on the pigmentation of the
      cells. Dct activity is 3-fold lower in slaty cells compared with non-agouti black
      melanocytes, whereas slaty light melanocytes have a surprisingly 28-fold lower
      Dct activity. Homology modelling of the active site of Dct suggests that the
      slaty mutation [R194Q (Arg194-->Gln)] is located in the active site and may alter
      the ability of the enzyme to transform the substrate. Transmembrane prediction
      methods indicate that the slaty light mutation [G486R (Gly486-->Arg)] may result
      in the sliding of the transmembrane domain towards the N-terminus, thus
      interfering with Dct function. Chemical analysis showed that both Dct mutations
      increase pheomelanin and reduce eumelanin produced by melanocytes in culture.
      Thus the enzymatic activity of Dct may play a role in determining whether the
      eumelanin or pheomelanin pathway is preferred for pigment biosynthesis.

PMID- 15960610
TI  - Regulation of cell survival by lipid phosphate phosphatases involves the
      modulation of intracellular phosphatidic acid and sphingosine 1-phosphate pools.
AB  - We have shown previously that LPPs (lipid phosphate phosphatases) reduce the
      stimulation of the p42/p44 MAPK (p42/p44 mitogen-activated protein kinase)
      pathway by the GPCR (G-protein-coupled receptor) agonists S1P (sphingosine 1
      phosphate) and LPA (lysophosphatidic acid) in serum-deprived HEK-293 cells
      [Alderton, Darroch, Sambi, McKie, Ahmed, N. J. Pyne and S. Pyne (2001) J. Biol.
      Chem. 276, 13452-13460]. In the present study, we now show that this can be
      blocked by pretreating HEK-293 cells with the caspase 3/7 inhibitor, Ac-DEVD-CHO
      [N-acetyl-Asp-Glu-Val-Asp-CHO (aldehyde)]. Therefore LPP2 and LPP3 appear to
      regulate the apoptotic status of serum-deprived HEK-293 cells. This was supported
      further by: (i) caspase 3/7-catalysed cleavage of PARP [poly(ADP-ribose)
      polymerase] was increased in serum-deprived LPP2-overexpressing compared with
      vector-transfected HEK-293 cells; and (ii) serum-deprived LPP2- and LPP3
      overexpressing cells exhibited limited intranucleosomal DNA laddering, which was
      absent in vector-transfected cells. Moreover, LPP2 reduced basal intracellular
      phosphatidic acid levels, whereas LPP3 decreased intracellular S1P in serum
      deprived HEK-293 cells. LPP2 and LPP3 are constitutively co-localized with SK1
      (sphingosine kinase 1) in cytoplasmic vesicles in HEK-293 cells. Moreover, LPP2
      but not LPP3 prevents SK1 from being recruited to a perinuclear compartment upon
      induction of PLD1 (phospholipase D1) in CHO (Chinese-hamster ovary) cells. Taken
      together, these data are consistent with an important role for LPP2 and LPP3 in
      regulating an intracellular pool of PA and S1P respectively, that may govern the
      apoptotic status of the cell upon serum deprivation.

PMID- 15960611
TI  - A direct, continuous, sensitive assay for protein disulphide-isomerase based on
      fluorescence self-quenching.
AB  - PDI (protein disulphide-isomerase) activity is generally monitored by insulin
      turbidity assay or scrambled RNase assay, both of which are performed by UV
      visible spectroscopy. In this paper, we present a sensitive fluorimetric assay
      for continuous determination of disulphide reduction activity of PDI. This assay
      utilizes the pseudo-substrate diabz-GSSG [where diabz stands for di-(o
      aminobenzoyl)], which is formed by the reaction of isatoic anhydride with the two
      free N-terminal amino groups of GSSG. The proximity of two benzoyl groups leads
      to quenching of the diabz-GSSG fluorescence by approx. 50% in comparison with its
      non-disulphide-linked form, abz-GSH (where abz stands for o-aminobenzoyl).
      Therefore the PDI-dependent disulphide reduction can be monitored by the increase
      in fluorescence accompanying the loss of proximity-quenching upon conversion of
      diabz-GSSG into abz-GSH. The apparent K(m) of PDI for diabz-GSSG was estimated to
      be approx. 15 muM. Unlike the insulin turbidity assay and scrambled RNase assay,
      the diabz-GSSG-based assay was shown to be effective in determining a single
      turnover of enzyme in the absence of reducing agents with no appreciable blank
      rates. The assay is simple to perform and very sensitive, with an estimated
      detection limit of approx. 2.5 nM PDI, enabling its use for the determination of
      platelet surface PDI activity in crude sample preparations.

PMID- 15960612
TI  - New insights into plant transaldolase.
AB  - The oxidative pentose phosphate pathway (OPPP) provides plants with important
      substrates for both primary and secondary metabolism via the oxidation of glucose
      6-phosphate. The OPPP is also thought to generate large amounts of reducing power
      to drive various anabolic processes. In animals this major pathway is located
      within the cytoplasm of cells, but in plants its subcellular compartmentation is
      far from clear. Although several enzymes of the OPPP were demonstrated to have
      both cytosolic and plastidic counterparts, there is yet no evidence for a full
      set of functional enzymes in each compartment. We report here the isolation of
      two coding sequences from tomato (Lycopersicon esculentum L.) which encode
      phylogenetically distant sequences (ToTal1 and ToTal2) that putatively encode
      distinct plastidic TA isoforms. The kinetic characterization of ToTal1 revealed
      that, unlike other enzymes of the non-oxidative branch of the OPPP, ToTal1 does
      not follow a Michaelis-Menten mode of catalysis which has implications for its
      role in regulating carbon flux between primary and secondary metabolism. TA genes
      appear to be differentially regulated at the level of gene expression in plant
      tissues and in response to environmental factors which suggests that TA isoforms
      have a non-overlapping role for plant metabolism.

PMID- 15960613
TI  - Osmotic regulation of root system architecture.
AB  - Although root system architecture is known to be highly plastic and strongly
      affected by environmental conditions, we have little understanding of the
      underlying mechanisms controlling root system development. Here we demonstrate
      that the formation of a lateral root from a lateral root primordium is repressed
      as water availability is reduced. This osmotic-responsive regulatory mechanism
      requires abscisic acid (ABA) and a newly identified gene, LRD2. Mutant analysis
      also revealed interactions of ABA and LRD2 with auxin signaling. Surprisingly,
      further examination revealed that both ABA and LRD2 control root system
      architecture even in the absence of osmotic stress. This suggests that the same
      molecules that mediate responses to environmental cues can also be regulators of
      intrinsic developmental programs in the root system.

PMID- 15960614
TI  - AUXIN RESPONSE FACTOR 2 (ARF2): a pleiotropic developmental regulator.
AB  - AUXIN RESPONSE FACTORS (ARFs) regulate auxin-mediated transcriptional
      activation/repression. They are encoded by a gene family in Arabidopsis, and each
      member is thought to play a central role in various auxin-mediated developmental
      processes. We have characterized three arf2 mutant alleles, arf2-6, arf2-7 and
      arf2-8. The mutants exhibit pleiotropic developmental phenotypes, including
      large, dark green rosette leaves, delayed flowering, thick and long
      inflorescence, abnormal flower morphology and sterility in early formed flowers,
      large organ size and delayed senescence and abscission, compared with wild-type
      plants. In addition, arf2 mutant seedlings have elongated hypocotyls with
      enlarged cotyledons under various light conditions. The transcription of ACS2,
      ACS6 and ACS8 genes is impaired in the developing siliques of arf2-6. The
      phenotypes of all three alleles are similar to those of the loss-of-function
      mutants obtained by RNA interference or co-suppression. There is no significant
      effect of the mutation on global auxin-regulated gene expression in young
      seedlings, suggesting that ARF2 does not participate in auxin signaling at that
      particular developmental stage of the plant life cycle. Because ARF2 is thought
      to function as a transcriptional repressor, the prospect arises that its
      pleiotropic effects may be mediated by negatively modulating the transcription of
      downstream genes in signaling pathways that are involved in cell growth and
      senescence.

PMID- 15960615
TI  - ARL1, a LOB-domain protein required for adventitious root formation in rice.
AB  - Adventitious roots constitute the bulk of the fibrous root system in cereals.
      Compared with the current understanding of shoot development, knowledge of the
      molecular mechanisms of development of the adventitious roots of cereals is
      limited. We have isolated and characterized a novel gene controlling the
      initiation of adventitious root primordia in rice (Oryza sativa L.). The gene,
      designated Adventitious rootless1 (ARL1), encodes a protein with a LATERAL ORGAN
      BOUNDARIES (LOB) domain. It is expressed in lateral and adventitious root
      primordia, tiller primordia, vascular tissues, scutellum, and young pedicels.
      ARL1 is a nuclear protein and can form homodimers. ARL1 is an auxin- and ethylene
      responsive gene, and the expression pattern of ARL1 in roots parallels auxin
      distribution. Our findings suggest that ARL1 is an auxin-responsive factor
      involved in auxin-mediated cell dedifferentiation, and that it promotes the
      initial cell division in the pericycle cells adjacent to the peripheral vascular
      cylinder in the stem.

PMID- 15960616
TI  - Spontaneously occurring mutations in the cyclobutane pyrimidine dimer photolyase
      gene cause different sensitivities to ultraviolet-B in rice.
AB  - Sensitivity to ultraviolet-B (UVB) radiation (280-320 nm) varies widely among
      rice cultivars. We previously indicated that UV-resistant rice cultivars are
      better able to repair cyclobutane pyrimidine dimers (CPDs) through photorepair
      than are UV-sensitive cultivars. In this paper, we report that UVB sensitivity in
      rice, in part, is the result of defective CPD photolyase alleles. Surjamkhi
      (indica) exhibited greater sensitivity to UVB radiation and was more deficient in
      CPD photorepair ability compared with UV-resistant Sasanishiki (japonica). The
      deficiency in CPD photorepair in Surjamkhi resulted from changes in two
      nucleotides at positions 377 and 888 in the photolyase gene, causing alterations
      of two deduced amino acids at positions 126 and 296 in the photolyase enzyme. A
      linkage analysis in populations derived from Surjamkhi and Sasanishiki showed
      that UVB sensitivity is a quantitative inherited trait and that the CPD
      photolyase locus is tightly linked with a quantitative trait locus that explains
      a major portion of the genetic variation for this trait. These results suggest
      that spontaneously occurring mutations in the CPD photolyase gene cause different
      degrees of sensitivity to UVB in rice, and that the resistance of rice to UVB
      radiation could be increased by increasing the photolyase function through
      conventional breeding or bioengineering.

PMID- 15960617
TI  - The transcription factor AtGRF5 and the transcription coactivator AN3 regulate
      cell proliferation in leaf primordia of Arabidopsis thaliana.
AB  - The development of the flat morphology of leaf blades is dependent on the control
      of cell proliferation as well as cell expansion. Each process has a polarity with
      respect to the longitudinal and transverse axes of the leaf blade. However, only
      a few regulatory components of these processes have been identified to date. We
      have characterized two genes from Arabidopsis thaliana: ANGUSTIFOLIA3 (AN3),
      which encodes a homolog of the human transcription coactivator SYT, and GROWTH
      REGULATING FACTOR5 (AtGRF5), which encodes a putative transcription factor. AN3
      is identical to GRF-INTERACTING FACTOR1 (AtGIF1). The an3 and atgrf5 mutants
      exhibit narrow-leaf phenotypes due to decreases in cell number. Conversely, cell
      proliferation in leaf primordia is enhanced and leaves grow larger than normal
      when AN3 or AtGRF5 is overexpressed. Both genes are expressed in leaf primordia,
      and in the yeast two-hybrid assay, the gene products were found to interact with
      each other through their N-terminal domains. These results suggest that AN3 and
      AtGRF5 act together and are required for the development of appropriate leaf size
      and shape through the promotion and/or maintenance of cell proliferation activity
      in leaf primordia.

PMID- 15960618
TI  - Arabidopsis IQD1, a novel calmodulin-binding nuclear protein, stimulates
      glucosinolate accumulation and plant defense.
AB  - Glucosinolates are a class of secondary metabolites with important roles in plant
      defense and human nutrition. To uncover regulatory mechanisms of glucosinolate
      production, we screened Arabidopsis thaliana T-DNA activation-tagged lines and
      identified a high-glucosinolate mutant caused by overexpression of IQD1
      (At3g09710). A series of gain- and loss-of-function IQD1 alleles in different
      accessions correlates with increased and decreased glucosinolate levels,
      respectively. IQD1 encodes a novel protein that contains putative nuclear
      localization signals and several motifs known to mediate calmodulin binding,
      which are arranged in a plant-specific segment of 67 amino acids, called the IQ67
      domain. We demonstrate that an IQD1-GFP fusion protein is targeted to the cell
      nucleus and that recombinant IQD1 binds to calmodulin in a Ca(2+)-dependent
      fashion. Analysis of steady-state messenger RNA levels of glucosinolate pathway
      genes indicates that IQD1 affects expression of multiple genes with roles in
      glucosinolate metabolism. Histochemical analysis of tissue-specific IQD1::GUS
      expression reveals IQD1 promoter activity mainly in vascular tissues of all
      organs, consistent with the expression patterns of several glucosinolate-related
      genes. Interestingly, overexpression of IQD1 reduces insect herbivory, which we
      demonstrated in dual-choice assays with the generalist phloem-feeding green peach
      aphid (Myzus persicae), and in weight-gain assays with the cabbage looper
      (Trichoplusia ni), a generalist-chewing lepidopteran. As IQD1 is induced by
      mechanical stimuli, we propose IQD1 to be novel nuclear factor that integrates
      intracellular Ca(2+) signals to fine-tune glucosinolate accumulation in response
      to biotic challenge.

PMID- 15960619
TI  - Plant 7SL RNA genes belong to type 4 of RNA polymerase III- dependent genes that
      are composed of mixed promoters.
AB  - The genes transcribed by RNA polymerase III (pol III) display a great diversity
      in terms of promoter structure and are placed in four groups accordingly. Type 3
      subset of pol III genes has promoter elements which reside entirely upstream of
      the coding region of the gene whereas type 4 consists of genes with mixed
      promoters that enclose intra- and extragenic regulatory sequences. Plant 7SL RNA
      genes have been previously classified as type 3 of pol III genes requiring an
      upstream sequence element and a canonical TATA box for transcriptional activity
      in transfected plant protoplasts. We have identified two novel functional control
      regions within the coding region of an Arabidopsis 7SL RNA gene (At7SL-1) that
      resemble tRNA gene-specific A and B boxes with respect to sequence and position.
      Single and multiple nucleotide substitutions in either of these regions resulted
      in a pronounced reduction of transcription activity in tobacco nuclear extract
      that was not caused by a decreased stability as shown by decay kinetics of wild
      type and mutant RNA transcripts. These findings suggest that plant 7SL RNA genes
      should be actually placed in type 4 of pol III-transcribed genes. As a
      consequence of substantially different upstream promoters utilized by plant and
      human pol III, in vitro transcription of 7SL RNA genes in heterologous systems is
      severely impaired. A chimeric human 7SL RNA gene that contains the 5' flanking
      region up to position -300 of At7SL-1 is yet transcribed with a reduced
      efficiency in tobacco extract when compared with the plant wild-type gene,
      supporting the notion that internal regulatory elements contribute to full
      activity.

PMID- 15960620
TI  - An important role of phosphatidic acid in ABA signaling during germination in
      Arabidopsis thaliana.
AB  - Phosphatidic acid (PA) functions as a lipid signaling molecule in plants.
      Physiological analysis showed that PA triggers early signal transduction events
      that lead to responses to abscisic acid (ABA) during seed germination. We
      measured PA production during seed germination and found increased PA levels
      during early germination. To investigate the role of PA during seed germination,
      we focused on the PA catabolic enzyme lipid phosphate phosphatase (LPP). LPP
      catalyzes the conversion of PA to diacylglycerol (DAG). There are 4 LPP genes in
      the Arabidopsis genome. Among them, AtLPP2 and AtLPP3 are expressed during seed
      germination. Two AtLPP2 T-DNA insertional mutants (lpp2-1 and lpp2-2) showed
      hypersensitivity to ABA and significant PA accumulation during germination.
      Furthermore, double-mutant analysis showed that ABA-insensitive 4 (ABI4) is
      epistatic to AtLPP2 but ABA-insensitive 3 (ABI3) is not. These results suggest
      that PA is involved in ABA signaling and that AtLPP2 functions as a negative
      regulator upstream of ABI4, which encodes an AP2-type transcription factor, in
      ABA signaling during germination.

PMID- 15960621
TI  - NPH4/ARF7 and ARF19 promote leaf expansion and auxin-induced lateral root
      formation.
AB  - Auxin response factors (ARFs) bind auxin response promoter elements and mediate
      transcriptional responses to auxin. Five of the 22 ARF genes in Arabidopsis
      thaliana encode ARFs with glutamine-rich middle domains. Four of these can
      activate transcription and have been ascribed developmental functions. We show
      that ARF19, the fifth Q-rich ARF, also activates transcription. Mutations in
      ARF19 have little effect on their own, but in combination with mutations in
      NPH4/ARF7, encoding the most closely related ARF, they cause several phenotypes
      including a drastic decrease in lateral and adventitious root formation and a
      decrease in leaf cell expansion. These results indicate that auxin induces
      lateral roots and leaf expansion by activating NPH4/ARF7 and ARF19. Auxin induces
      the ARF19 gene, and NPH4/ARF7 and ARF19 together are required for expression of
      one of the arf19 mutant alleles, suggesting that a positive feedback loop
      regulates leaf expansion and/or lateral root induction.

PMID- 15960622
TI  - Repression of light signaling by Arabidopsis SPA1 involves post-translational
      regulation of HFR1 protein accumulation.
AB  - Arabidopsis uses two major classes of photoreceptors to mediate seedling de
      etiolation. The cryptochromes (cry1 and cry2) absorb blue/ultraviolet-A light,
      whereas the phytochromes (phyA-phyE) predominantly regulate responses to red/far
      red light. Arabidopsis COP1 represses light signaling by acting as an E3
      ubiquitin ligase in the nucleus, and is responsible for targeted degradation of a
      number of photomorphogenesis-promoting factors, including HY5, LAF1, phyA, and
      HFR1. Distinct light signaling pathways initiated by multiple photoreceptors
      (including both phytochromes and cryptochromes) eventually converge on COP1,
      causing its inactivation and nuclear depletion. Arabidopsis SPA1, which encodes a
      protein structurally related to COP1, also represses light signaling under
      various light conditions. In this study, we present genetic evidence supporting
      that HFR1, which encodes a photomorphogenesis-promoting bHLH transcription
      factor, acts downstream of SPA1 and is required for different subsets of branch
      pathways of light signaling controlled by SPA1 under different light conditions.
      We show that SPA1 physically interacts with HFR1 in a yeast two-hybrid assay and
      an in vitro co-immunoprecipitation assay. We demonstrate that higher levels of
      HFR1 protein accumulate in the spa1 mutant background under various light
      conditions, including far-red, red, blue, and white light, whereas a marginal
      increase in HFR1 transcript level is only seen in dark- and far-red light-grown
      spa1-100 mutants. Together, our data suggest that repression of light signaling
      by Arabidopsis SPA1 likely involves post-translational regulation of HFR1 protein
      accumulation.

PMID- 15960623
TI  - Activation tagging of a gene for a protein with novel class of CCT-domain
      activates expression of a subset of sugar-inducible genes in Arabidopsis
      thaliana.
AB  - In the current studies, we examined sugar-inducible gene expression using the
      Arabidopsis thaliana line sGsL, which carries luciferase (LUC) and beta
      glucuronidase (GUS) reporter genes under the control of a 210-bp promoter derived
      from the sweet potato sporamin gene (Spo(min)). We isolated an enhancer
      activation-tagged mutant of this line that showed high-level expression of LUC
      and GUS under non-inducing low-sugar conditions. The Activator ofSpo(min)::LUC2
      (ASML2) gene located close to the enhancer encodes a protein belonging to a
      previously uncharacterized class of CCT (CONSTANS, CONSTANS-like, TOC1) domain
      proteins. Overexpression of ASML2 cDNA in the sGsL line resulted in enhanced
      expression of not only LUC and GUS reporters but also several endogenous sugar
      inducible genes, including Atbeta-Amy, ApL3, and VSP2. Transient co-expression of
      35S::ASML2 with the Spo(min)::LUC or Atbeta-Amy::LUC reporter in protoplasts
      resulted in an approximately 2.4 or 5.6-fold transactivation of LUC expression,
      respectively. Expression of ASML2 was high in reproductive organs, and expression
      in seedlings was slightly enhanced by sugars, but not by abscisic acid. These
      results suggest that ASML2 functions as a transcriptional activator and regulates
      the expression of at least a subset of sugar-inducible genes.

PMID- 15960624
TI  - The Botany Array Resource: e-Northerns, Expression Angling, and promoter
      analyses.
AB  - The Botany Array Resource provides the means for obtaining and archiving
      microarray data for Arabidopsis thaliana as well as biologist-friendly tools for
      viewing and mining both our own and other's data, for example, from the
      AtGenExpress Consortium. All the data produced are publicly available through the
      web interface of the database at http://bbc.botany.utoronto.ca. The database has
      been designed in accordance with the Minimum Information About a Microarray
      Experiment convention -- all expression data are associated with the
      corresponding experimental details. The database is searchable and it also
      provides a set of useful and easy-to-use web-based data-mining tools for
      researchers with sophisticated yet understandable output graphics. These include
      Expression Browser for performing 'electronic Northerns', Expression Angler for
      identifying genes that are co-regulated with a gene of interest, and Promomer for
      identifying potential cis-elements in the promoters of individual or co-regulated
      genes.

PMID- 15960625
TI  - Cutaneous manifestations of neurological diseases: review of neuro
      pathophysiology and diseases causing pruritus.
AB  - Pruritus does not always originate from stimulation to the skin associated with
      primary dermatological disorders. It may be caused by neurological or behavioural
      disorders. The essential role of the nervous system in the control (enhancement
      and inhibition) of pruritus and its pathophysiology are presented. In order to
      allow differentiation between dermatological and neurological disorders,
      inherited or acquired peripheral neuropathies and central nervous disorders
      (Arnold-Chiari syndrome, seizure-related disorders, central nervous system
      tumours) that may induce itch are discussed.

PMID- 15960626
TI  - Canine serum immunoreactivity to M. pachydermatis in vitro is influenced by the
      phase of yeast growth.
AB  - In western immunoblotting studies of canine sera using Malassezia pachydermatis
      extracts, the reported patterns of immunoreactivity vary between different
      laboratories. Because the duration of culture influences the antigenic
      composition of lipid-dependent Malassezia spp. when probed with human sera, we
      investigated whether the in vitro growth phase of M. pachydermatis influences
      immunoreactivity using canine sera. Extracts of M. pachydermatis CBS 1879 grown
      in Sabouraud's liquid medium at 37 degrees C for 2, 4, 6, 8 and 10 days were
      prepared by mechanical disruption, centrifugation, dialysis and lyophilization.
      Yeast growth phase was assessed by sequential colony counts and optical density
      measurements. Patterns of IgG immunoreactivity in high (n = 3) and low (n = 3)
      titre sera were compared using extracts prepared at each time point by sodium
      dodecyl sulphate polyacrylamide gel electrophoresis and western immunoblotting.
      Protein bands of 62 and 49 kDa were recognized by all sera, and 98 and 68 kDa
      bands were recognized by five sera. Proteins of 188, 66, 58, 57, 38, 28 and 17
      kDa were only recognized by high titre sera. All high titre sera used recognized
      more bands in exponential phase (d2) extracts when compared with decline phase
      (d8-d10) extracts, and two of these sera showed most bands in stationary phase
      (d4-d6) extracts. Bands of 62 and 57 kDa were primarily detected in exponential
      and early stationary phase extracts. There is variation in antigenic expression
      in different growth phases of M. pachydermatis, which might explain discrepancies
      between previous laboratory studies of canine immunity to this yeast.

PMID- 15960627
TI  - In vitro metabolism of progesterone by canine hair follicle cells.
AB  - Dermal papilla cells (DPC) and dermal fibroblasts (DFB) derived from hair
      follicles from two different body sites (head, flank) of four male, castrated
      beagle dogs were incubated for 24 h with radioactive progesterone (P4). Thin
      layer chromatography was used for separation and autoradiography for
      identification of the radioactive metabolites. In DFB the main metabolites were
      cortisol and 4-pregnene-11beta-ol-3,20-dione, whereas in DPC they were 5alpha
      pregnane-3,20-dione and cortisol. The highest percentage of metabolism of P4 was
      found in DFB of the head. Smaller amounts of other metabolites were found in both
      cell types of both locations.

PMID- 15960628
TI  - Species specificity in the adherence of staphylococci to canine and human
      corneocytes: a preliminary study.
AB  - Staphylococcal pyoderma is rarely contagious between dogs and humans, or humans
      and dogs. This study investigated the hypothesis that there are species
      differences in adherence of Staphylococcus intermedius (the most common isolate
      from dogs) and Staphylococcus aureus (the most common isolate from humans) to
      canine and human corneocytes. Sheets of corneocytes were collected from the
      ventral abdomen of 10 dogs and the medial forearm of 10 humans (all healthy and
      without any history or physical signs of skin disease) using double-sided tape.
      Staphylococcus intermedius from a case of canine bacterial pyoderma and a human
      strain of S. aureus were prepared in phosphate buffered saline (PBS) and applied
      in duplicate, respectively, to the canine and human corneocyte-covered tapes
      using PBS as negative control. After incubation, rinsing, and staining with
      crystal violet, quantification of the adherent bacteria was carried out blindly
      by computerized image analysis. Staphylococcus intermedius was found to adhere
      significantly more to canine corneocytes than S. aureus (P = 0.0006), whereas S.
      aureus showed greater adherence to human corneocytes than S. intermedius (P <
      0.0001). In addition, the pattern of adherence differed between the two
      organisms, with S. intermedius adhering to the entire surface and S. aureus
      adhering mainly to the periphery of both canine and human corneocytes. Preference
      for adherence to these two hosts may explain, in part, why S. intermedius and S.
      aureus are uncommonly isolated from human and canine skin infections,
      respectively.

PMID- 15960629
TI  - Effectiveness of low dose immunotherapy in the treatment of canine atopic
      dermatitis: a prospective, double-blinded, clinical study.
AB  - There are anecdotal reports of increased effectiveness of allergen-specific
      immunotherapy (ASIT) in dogs with doses of vaccine lower than that recommended by
      the manufacturers. However, no controlled studies have been carried out. The aim
      of this prospective, double-blinded study was to evaluate whether induction and
      maintenance with low dose (LD) ASIT resulted in a different success rate compared
      with the standard dose (SD). Twenty-seven dogs with confirmed atopic dermatitis
      were allocated by block randomization to two groups. One group (n = 13) received
      SD ASIT; the other group (n = 14) received LD ASIT (1/10 of the SD) following the
      same frequency protocol. Cases were graded at 0, 3, 6 and 9 months for clinical
      signs using a modified canine atopic dermatitis extent and severity index
      (mCADESI) and for pruritus using a 0-5 descriptor scale. There were no
      significant differences between the groups in the pruritus and mCADESI scores (P
      > 0.155) at the end of the study, and the changes in pruritus (P > 0.920) and
      mCADESI (P > 0.296) scores from the beginning to the end of the study were
      similar in both groups. Pruritus scores in both groups did not change during the
      study (P > 0.052). However, significant reductions in mCADESI scores were seen in
      both groups (P < 0.032). Six dogs achieved a final pruritus score of 0, six
      achieved a reduction in pruritus score and 15 did not improve or worsened. There
      was, therefore, no evidence that LD ASIT is more effective than the standard
      protocol.

PMID- 15960630
TI  - Comparison of the clinical efficacy of oral terbinafine and ketoconazole combined
      with cephalexin in the treatment of Malassezia dermatitis in dogs--a pilot study.
AB  - The purpose of this randomized, single blinded clinical trial was to evaluate
      cytologically and clinically the efficacy of oral cephalexin alone and its
      combination with terbinafine or ketoconazole for the treatment of Malassezia
      dermatitis in dogs. Twenty-two client-owned dogs with Malassezia dermatitis
      completed the 3-week study. All received cephalexin (generic, 250 mg or 500 mg)
      at 22-30 mg kg(-1) twice daily. Eight dogs received terbinafine at 30 mg kg(-1)
      once daily and seven dogs received ketoconazole (generic, 200 mg) at 5-10 mg kg(
      1) twice daily. The remaining seven dogs received cephalexin alone. At week 0
      (visit 1) and week 3 (visit 2), mean yeast counts were determined from three
      affected areas using tape-strip cytology, a clinical index score (CIS) was
      assigned to the affected areas, and owners evaluated pruritus using a visual
      analogue scale. All groups showed reduction in mean yeast counts, CIS and
      pruritus. There was an 86.8%, 80.2% and 28.8% reduction in mean yeast counts from
      visit 1 to visit 2 for the terbinafine, ketoconazole and cephalexin-only groups,
      respectively. However, within treatment group comparisons a significant reduction
      in mean yeast count was only evident for the terbinafine (P < 0.002) and
      ketoconazole (P < 0.01) groups. Pruritus reduction was only significant for the
      terbinafine group. These preliminary results suggest that terbinafine should be
      further assessed for the treatment of canine Malassezia dermatitis.

PMID- 15960631
TI  - Sarcoptic mange in free-ranging raccoon dogs (Nyctereutes procyonoides) in Japan.
AB  - Sarcoptes scabiei infestation was diagnosed in three freshly dead free-ranging
      raccoon dogs (Nyctereutes procyonoides) in Kanagawa Prefecture, Japan. The dogs
      presented with an alopecic pruritic skin disease, with signs of alopecia on the
      ears, muzzle, around the eyes, elbow, thigh and the neck, and hyperpigmented and
      crusted skin lesions, which had a severe malodour. Skin scrapings revealed the
      presence of the mite Sarcoptes scabiei. Histopathology of lesions demonstrated
      marked acanthosis, hyperkeratosis, parakeratosis and fungal elements, which were
      subsequently identified as Acremonium sp., Alternaria sp. and an unknown fungus.
      Mite segments were located mainly in the stratum corneum and also in the stratum
      granulosum. Tunnels could be observed in the hyperkeratotic stratum corneum.
      Scanning electron microscopy (SEM) revealed the tortoise-like Sarcoptes scabiei
      with four long bristles, suckers and blade-like claws on legs 1 and 2, cuticular
      spines, prominent body striations and a terminal anus. SEM also revealed an adult
      female mite digging a tunnel with the head wedged into the very end of the closed
      burrow. Tunnels filled with eggshells, corneocyte debris and faecal pellets were
      also observed.

PMID- 15960632
TI  - Cutaneous metastases of a bronchial adenocarcinoma in a cat.
AB  - This case report describes a cat with metastasis of a bronchial adenocarcinoma to
      the abdominal skin. The cat had been treated with antibiotics and corticosteroids
      for several episodes of coughing when it acutely developed erythema, pustules and
      plaques on the abdominal skin. Diagnosis was based on cytological examination of
      fine-needle aspirates of cutaneous pustules, X-ray examination of the thorax and
      histological examination of skin biopsy samples. As the prognosis was poor, the
      cat was euthanased. Necropsy findings confirmed the diagnosis. Cutaneous
      metastases of lung carcinoma are rare in cats but have been reported in the
      digits with underlying bone involvement. To the authors' knowledge, this is the
      first report of metastasis of a feline bronchial carcinoma to the ventral skin.

PMID- 15960633
TI  - Papular dermatitis due to Leishmania spp. infection in dogs with parasite
      specific cellular immune responses.
AB  - Papular dermatitis due to Leishmania spp. infection was diagnosed in three boxers
      and two Rottweilers with Leishmania-specific cellular immunity. Diagnosis was
      based on histological and immunohistochemical examination of papules in four dogs
      and on cytological examination in one dog. Serum protein electrophoresis was
      within reference ranges and low antibody levels to Leishmania infantum were
      detected. Delayed-type hypersensitivity (DTH) reaction to leishmanin was
      evaluated before treatment in three dogs with positive results. After meglumine
      antimoniate therapy for 3 to 4 weeks and allopurinol treatment for 6 to 10
      months, all dogs were clinically normal, had positive DTH reactions to leishmanin
      and reduced antibody titres. In conclusion, we suggest that this previously
      unreported cutaneous presentation of canine leishmaniosis appears to be
      associated with specific immunocompetence and, consequently, with a favourable
      prognosis.

PMID- 15960635
TI  - Preoperative blood pressure management of children with catecholamine-secreting
      tumors: time for a change.

PMID- 15960636
TI  - Thoracoscopic repair of esophageal atresia with tracheoesophageal fistula:
      anesthetic and intensive care management of a series of eight neonates.
AB  - Advances in minimally invasive techniques have made pediatric laparoscopic
      surgery commonplace. Thoracoscopic surgery in children however is still performed
      in only a few centers throughout the world. Between July 2001 and January 2004,
      the first eight esophageal atresia with tracheoesophageal fistula repairs were
      performed thoracoscopically at the Royal Hospital for Sick Children in Edinburgh.
      This article presents their anesthetic management, their postoperative management
      in the pediatric intensive care unit and reviews the complications seen in both
      the intraoperative and postoperative periods. Finally we discuss how our
      experience to date influences our perioperative management of these challenging
      cases.

PMID- 15960637
TI  - Giving parents written information about children's anesthesia: are setting and
      timing important?
AB  - BACKGROUND: Research indicates that parents wish to receive more information and
      are anxious about anesthesia prior to their child's surgery. METHODS: A pilot
      randomized controlled trial was conducted to ascertain if parents who received a
      general anesthesia information leaflet by post 1 week following their presurgical
      assessment clinic visit (n = 19) had greater knowledge, reduced anxiety, or
      greater satisfaction with anesthetic information on the day of surgery than
      parents who received the leaflet at the clinic visit (n = 21). RESULTS: Parents
      had important knowledge deficits on the day of surgery, despite receiving the
      leaflet in addition to standard verbal communication. Parents who were given the
      leaflet at the presurgical assessment clinic had a modest 10% increase in
      knowledge compared with parents who received the leaflet by post. However,
      parents who received the leaflet within 2 weeks for their child's surgery also
      had 10% greater knowledge, regardless of the method of delivery. There were no
      differences in parental anxiety or satisfaction with the information related to
      method or timing of delivery. Parents appreciated receiving written information
      and a slight majority of parents (56%) preferred to receive the information at
      the presurgical assessment clinic visit. CONCLUSIONS: Parents have unmet
      information needs related to children's anesthetic care. Written information may
      improve parent knowledge and enhance satisfaction, but the setting and timing of
      information delivery are also important to consider.

PMID- 15960638
TI  - Comparative evaluation of midazolam and ketamine with midazolam alone as oral
      premedication.
AB  - BACKGROUND: Oral premedication with midazolam and ketamine is widely used in
      pediatric anesthesia to reduce emotional trauma and ensure smooth induction.
      However, various dosing regimens when used alone or in combination have variable
      efficacy and side effect profile. The aim of our study was to investigate and
      compare the efficacy of oral midazolam alone with a low-dose combination of oral
      midazolam and ketamine. METHODS: We performed a prospective randomized double
      blind study in 100 children who were randomly allocated into two groups. Group M
      received 0.5 mg.kg(-1) oral midazolam and group MK received 0.25 mg.kg(-1) oral
      midazolam with 2.5 mg.kg(-1) oral ketamine. The preoperative sedation score, ease
      of parental separation and ease of mask acceptance were evaluated on a 4-point
      scale. The time to recovery from anesthesia and to achieve satisfactory Aldrete
      score was also noted. RESULTS: Uniform and acceptable sedation scores were seen
      in both the groups (group M 95.9%; group MK 97.96%), without any serious side
      effects. However, the combination offered significantly more children in an
      awake, calm and quiet state, who were easily separated from their parents (73.46%
      in MK vs 41% in group M). The induction scores were comparable between the
      groups. The recovery room characteristics and time to achieve satisfactory
      Aldrete score were also comparable between the two groups. CONCLUSIONS: Oral
      midazolam alone and a combination of midazolam with ketamine provide equally
      effective anxiolysis and separation characteristics. However, the combination
      provided more children in an awake, calm and quiet state who could be separated
      easily from parents.

PMID- 15960639
TI  - Marked variation in oxycodone pharmacokinetics in infants.
AB  - BACKGROUND: The pharmacokinetics of oxycodone (13-hydroxy-7,8-dihydrocodeinone)
      has been studied in adults and in children who are older than 6 months but there
      is no information on the disposition of oxycodone in neonates and young infants.
      The aim of this study was to study the pharmacokinetics of oxycodone in infants
      varying in age from 0 to 6 months. METHODS: Twenty-two infants undergoing surgery
      were given postoperatively an intravenous bolus of 0.1 mg.kg(-1) of oxycodone
      hydrochloride. Ten of the patients were younger than 1 week (group 1), six from 1
      week to 2 months (group 2) and six from 2 to 6 months (group 3). Plasma samples
      were collected for the analysis of oxycodone concentrations up to 24 h.
      Pharmacokinetics were characterized by noncompartmental methods. RESULTS: The
      median (range) values for the clearance (Cl) were 9.9 (2.3-17.2), 20.1 (3.7-40.4)
      and 15.4 (14.8-80.2) ml.min(-1).kg(-1) in the above three groups. The values for
      volume of distribution at steady-state were 3.3 (1.9-4.7), 5.6 (1.3-8.5) and 3.2
      (1.8-6.0) l.kg(-1) and for elimination half-life (t(1/2)) 4.4 (2.4-14.1), 3.6
      (1.6-11.6) and 2.0 (0.8-3.9) h, respectively. Both Cl (r = 0.46) and half-life (r
      = -0.46) were correlated to the age of the patient (P < 0.05). There were 13
      patients who were on mechanical ventilation at the time of oxycodone
      administration. None of the spontaneously breathing infants had hypoventilation
      which required assistance during the study. CONCLUSIONS: The values for Cl and
      t(1/2) varied greatly between the subjects. This variability was most pronounced
      in the two youngest groups. Routine dosing of oxycodone in young infants may be
      dangerous. The dose of oxycodone must be titrated individually.

PMID- 15960640
TI  - Perioperative pharmacokinetics of ibuprofen enantiomers after rectal
      administration.
AB  - BACKGROUND: Ibuprofen is a nonsteroidal anti-inflammatory drug which has both
      peripheral and central analgesic effects. Ibuprofen has been shown to be an
      effective antipyretic and postoperative analgesic drug both in adults and
      children with few side effects. Pharmacokinetics of rectal ibuprofen has not been
      studied, although suppositories are frequently used for perioperative pain
      control in children. METHODS: There were four study groups: full-term infants
      aged 1-7 weeks (n = 9), infants aged 8-25 weeks (n = 8), and infants aged 26-52
      weeks (n = 7). Adult patients were 20-40 years old (n = 7). Ibuprofen suppository
      20 mg.kg(-1) was administered after induction of anesthesia. Blood samples were
      collected from 20 min to 10 h after dosing and pharmacokinetic analysis of
      ibuprofen enantiomers were done. RESULTS: Both ibuprofen enantiomers were
      detectable in blood in 20 min. Total ibuprofen plasma concentrations >10 mg.l(-1)
      were seen from 40 min to 8 h. Values for T(max) of ibuprofen enantiomers and
      total ibuprofen were higher in the adult group than any of the infant groups (P <
      0.05). In addition, values for physiological (standardized) t(1/2) of (R)-(-)-
      and (S)-(+)-ibuprofen were higher in infants aged 1-7 weeks than the adults (P <
      0.05). None of the other pharmacokinetic variables, C(max), AUC, chronological
      t(1/2) or AUC ratio differed between the groups. CONCLUSIONS: A single dose of
      ibuprofen suppository 20 mg.kg(-1) after induction of anesthesia guarantees
      analgesic plasma concentrations during the early postoperative period. Except for
      the delayed absorption of ibuprofen in adults and higher physiological t(1/2) in
      infants aged 1-7 weeks, no major pharmacokinetic differences were observed
      between study groups.

PMID- 15960641
TI  - Risk factors influencing inadvertent hypothermia in infants and neonates during
      anesthesia.
AB  - BACKGROUND: The factors affecting the thermal status in neonates and infants
      undergoing general anesthesia are not yet investigated in detail. We evaluated
      the factors leading to intraoperative hypothermia in 60 neonates and infants.
      METHODS: The initial body temperatures and the core temperatures at the 10th,
      30th, 60th and 90th minute of anesthesia, as well as at the end of the operation
      were recorded. The patients were divided into the groups according to the age,
      type of surgery (minor vs major), operating room (OR) temperatures (low '<23
      degrees C' vs high '>23 degrees C') and the initial core temperature of the
      patients. RESULTS: In 31 neonates and 29 infants, the mean core temperatures
      decreased 10 min after anesthesia induction. In all neonates and in infants with
      'low OR temperature' (<23 degrees C), these decreases continued to the end of the
      surgery. Except infants undergoing minor surgery, in all patients, the core
      temperatures at the end of surgery were lower than the baseline temperature. The
      greatest decrease in core temperatures occurred in neonates undergoing major
      surgery and with low OR temperature. In low OR temperature, the decrease of core
      temperature is higher in patients with major surgery. In patients undergoing
      minor surgery, the decrease of core temperature is more in neonates than infants.
      Major surgery increased the chance of decrease of the core temperature by 2.66
      times and operating room temperature less than 23 degrees C by 1.96 times.
      CONCLUSION: The type of surgery and the OR temperature are the main factors for
      decrease of the core temperature in neonates and infants. In neonates, the core
      temperatures are less stable, regardless of OR temperature and type of surgery.
      In high OR temperature, infants can stabilize their core temperature better than
      neonates.

PMID- 15960642
TI  - Comparison of the effects of clonidine and ketamine added to ropivacaine on
      stress hormone levels and the duration of caudal analgesia.
AB  - BACKGROUND: The purpose of this study was to compare the analgesic quality and
      duration of ropivacaine 0.2% with the addition of clonidine (1 microg.kg(-1))
      with that of ropivacaine 0.2% and the addition of ketamine (0.5 mg.kg(-1)) to
      that of ropivacaine 0.2% and also compare the postoperative cortisol, insulin and
      glucose concentrations, sampled after induction and 1 h later following caudal
      administration in children. METHODS: According to the randomization, patients in
      the ropivacaine group (R; n = 25) received ropivacaine 0.2%, 0.75 ml.kg(-1);
      those in the clonidine group (RC; n = 25) received ropivacaine 0.2% 0.75 ml.kg(
      1) plus clonidine 1 microg.kg(-1) and those in the ketamine/ropivacaine group
      (RK; n = 25) ropivacaine 0.2% 0.75 ml.kg(-1) plus ketamine 0.5 mg.kg(-1) (10
      mg.ml(-1) concentration). Drugs were diluted in 0.9% saline (0.75 ml.kg(-1)) and
      prepared by a staff anesthesiologist not otherwise involved in the study. In all
      groups, the duration of analgesia, analgesic requirements, sedation and insulin,
      glucose, cortisol concentrations were recorded and statistically compared.
      RESULTS: There were no significant differences among the three study groups with
      respect to age, weight or duration of surgery. Caudal administration of clonidine
      1 microg.kg(-1) or ketamine 0.5 mg.kg(-1) induced a longer duration of analgesia
      (P < 0.05) compared with ropivacaine alone. Insulin levels were increased and
      cortisol reduced in all groups. Glucose concentration was increased in all groups
      and statistically significant (P < 0.05). CONCLUSIONS: Addition of ketamine and
      clonidine to ropivacaine 0.2% 0.75 ml.kg(-1), when administered caudally in
      children, prolongs the duration of postoperative analgesia. The need for
      subsequent postoperative analgesic is also reduced. Caudal analgesia attenuates
      or allows partial changes to postoperative cortisol, insulin or blood glucose
      responses to surgery.

PMID- 15960643
TI  - Clonidine administered as adjuvant for bupivacaine in ilioinguinal
      iliohypogastric nerve block does not prolong postoperative analgesia.
AB  - BACKGROUND: Coadministration of clonidine with local anesthetics is associated
      with improvement of the quality of peripheral nerve block and significant
      prolongation of postoperative analgesia. Better analgesia has been reported with
      clonidine in ilioinguinal nerve block compared with caudal use. The object of
      this study was to determine whether adding of 1 microg.kg(-1) clonidine to
      bupivacaine 0.25% in ilioinguinal-iliohypogastric nerve block prolongs
      postoperative analgesia in children. METHODS: Ninety-eight children ASA I-II aged
      between 1 and 12 years, scheduled for elective outpatient herniorrhaphy or
      orchidopexy were randomly allocated to receive an ilioinguinal-iliohypogastric
      nerve block either with 0.3 ml.kg(-1) bupivacaine 0.25% plus 1 microg.kg(-1)
      clonidine or only bupivacaine. Postoperative analgesic needs, time to the first
      analgesic supplementation and sedation score were assessed in hospital for 6 h
      postoperatively and at home by telephone call. RESULTS: Demographic data were
      similar in both groups. There was no statistical difference in the rate of rescue
      analgesia between the two groups during the first six postoperative hours (20.4%
      group clonidine vs 30.6% group no clonidine) (P = 0.17). A slight decrease in
      systolic blood pressure during surgery was reported in the clonidine group. There
      was no difference in the scores of sedation between the two groups. At home, 10
      patients in the clonidine group and nine patients in the nonclonidine group
      received analgesic medication. There was no difference between the two groups
      regarding the number of patients receiving analgesic rescue during the first 24 h
      (log rank = 0.39). Parental satisfaction was high in both groups. CONCLUSIONS:
      Our study failed to demonstrate any advantage in addition of 1 microg.kg(-1)
      clonidine to 0.25% bupivacaine for ilioinguinal-iliohypogastric nerve block
      compared with bupivacaine 0.25% alone.

PMID- 15960644
TI  - A survey of the use of capnography for the confirmation of correct placement of
      tracheal tubes in pediatric intensive care units in the UK.
AB  - BACKGROUND: The Royal College of Anaesthetists and the Association of
      Anaesthetists of Great Britain and Ireland recommend the use of capnography to
      ensure correct tracheal tube placement in the theater environment. Correct
      tracheal tube placement is essential in the care of ventilated patient, even more
      vital if the patient is critically ill, if serious morbidity and mortality is to
      be avoided. This survey examined the availability and use of capnography to
      confirm correct tracheal tube placement in the pediatric intensive care unit
      (PICU) in the UK. METHODS: A questionnaire concerning the use of capnography to
      confirm tracheal tube placement were sent to the lead clinicians of every PICU in
      the UK. RESULTS: A total of 19 replies were received from 26 (73%) consultants.
      One unit did not have a capnograph, 13 units (68%) had one capnograph for several
      beds and five units (26%) had one capnograph for each bed. Two units (11%) used
      capnography for every intubation and in 10 units (52%) the use of capnography was
      dependent on individual physician preference. Eight consultants (42%) felt that
      confirming tracheal tube placement by capnography should be mandatory after every
      intubation whether in the ward, A & E, or PICU. A total of 89% of PICUs have
      trainees with <1 year anesthetic experience compared with 65% of adult ICUs.
      CONCLUSIONS: The use of capnography to confirm tracheal tube placement may be
      even more important in the PICU than in adult ICU.

PMID- 15960645
TI  - Delayed onset refractory dystonic movements following propofol anesthesia.
AB  - Neuroexcitation is an uncommon but well recognized side effect of propofol
      anesthesia and sedation. We present a patient who, despite an intact mental
      status and without any preexisting movement disorder, experienced delayed onset
      of involuntary dystonic movements involving head, neck and shoulder for 11 h
      following emergence from propofol/nitrous oxide anesthesia.

PMID- 15960646
TI  - Use of CobraPLA for airway management in a neonate with Desbuquois syndrome. Case
      report and anesthetic implications.
AB  - We present the anesthetic management of an infant with Desbuquois syndrome (a
      rare form of micromelic dwarfism) with a possible difficult airway. The
      anesthetic implications of this syndrome are presented. The airway was managed
      with a new supraglottic device - the CobraPLA. Although intubation through this
      device was not possible in this instance, CobraPLA provided a satisfactory
      supraglottic airway. It was easy to insert and provided satisfactory conditions
      for positive pressure ventilation. The CobraPLA provides another option for
      airway management.

PMID- 15960647
TI  - Perioperative management of a child with severe hypertension from a catecholamine
      secreting neuroblastoma.
AB  - Increased catecholamine secretion from neuroblastomas can occasionally be
      demonstrated, but severe hypertension is uncommon. We report the perioperative
      management of a 5 year old child with stage III adrenal neuroblastoma who
      presented with malignant hypertension and high norepinephrine and dopamine
      levels. Hypertensive crises occurred during anesthesia for surgical biopsy and
      during chemotherapy. After blood pressure control using phenoxybenzamine and
      enalapril, doxazosin was used successfully as the preoperative alpha-adrenergic
      receptor antagonist for surgical tumor resection.

PMID- 15960648
TI  - Acute quadriplegic myopathy in a 16-month-old child.
AB  - We present a case of a 16-month old previously healthy child who was hospitalized
      because of an acute respiratory insufficiency most likely caused by a viral
      infection and who then developed a severe acute quadriplegic myopathy (AQM).
      Initial clinical symptoms were respiratory acidosis, dypnea, intense wheezing,
      and deterioration of the level of consciousness, which required orotracheal
      intubation and mechanical ventilation. We administered neuromuscular blocking
      agents, corticosteroids, and antibiotics. After 9 days the clinical picture
      improved. An attempt to wean from the ventilator failed. We diagnosed AQM. This
      paper discusses AQM and its clinical importance.

PMID- 15960649
TI  - Prolonged infusion of dexmedetomidine for sedation following tracheal resection.
AB  - Dexmedetomidine is a centrally acting alpha-2 adrenergic agonist that is
      currently approved by the US Food and Drug Administration for short-term use (<
      or = 24 h) to provide sedation in adults in the ICU. This drug has been shown to
      be efficacious in adult medical and surgical patients in providing sedation,
      anxiolysis, and analgesia. Dexmedetomidine has been associated with rapid onset
      and offset, hemodynamic stability, and a natural, sleep-like state in
      mechanically ventilated adults. To date, there are few publications of the use of
      this drug in children, and prolonged infusion has not been described. We report
      our use of dexmedetomidine in a child during a 4-day period of mechanical
      ventilation following tracheal reconstruction for subglottic stenosis.

PMID- 15960650
TI  - Minimizing trauma of feeding tube exchange in patients with bleeding diathesis.

PMID- 15960651
TI  - Modified airway mask as an aid for fibroptic tracheal intubation.

PMID- 15960652
TI  - Subglottic fibrinous cast.

PMID- 15960653
TI  - Very low dose of caudal morphine.

PMID- 15960654
TI  - Sepsis after epidural catheterization in a child with chronic regional pain
      syndrome type I.

PMID- 15960655
TI  - An examination of the intestinal tract of Atlantic salmon, Salmo salar L., parr
      fed different varieties of soy and maize.
AB  - This study was conducted to investigate the long-term effects of feeding plant
      products from both traditional breeding and from biotechnology on intestinal
      somatic indices, histology and cell proliferation in first-feeding Atlantic
      salmon, Salmo salar L. (initial weight 0.21 +/- 0.02 g). A standard fishmeal diet
      (standard fishmeal) was formulated to contain fishmeal as the sole protein source
      and suprex maize as the main starch source. Six experimental diets were then
      developed: two in which some of the fishmeal was replaced with commercially
      available, genetically modified Roundup Ready full-fat soybean meal (GM-soy) or
      commercially available, non-GM full-fat soybean meal (nGM-soy) at a level of
      12.5% of the total diet, and four diets in which the suprex maize was replaced
      with two lines of GM-maize (Dekalb 1; D1 and Pioneer 1; P1), both products of
      event MON810, and their half-sibling non-GM counterparts (Dekalb 2; D2 and
      Pioneer 2; P2), at a level of 12.1% of total diet. Each diet was fed to fish in
      triplicate tanks and the experiment lasted for 8 months, during which the fish
      reached a final weight of 101-116 g. There was no significant effect of diet on
      the intestinal indices, nor were histological changes observed in the pyloric
      caeca or mid intestine. In the distal intestine, one of nine sampled fish fed nGM
      soy showed moderate changes, two of nine sampled fish fed GM-soy showed changes,
      one with moderate and one with severe changes, and two of nine fish fed nGM-maize
      D2 had moderate changes. Using a monoclonal antibody against proliferating cell
      nuclear antigen (PCNA), cell proliferative responses to the experimental diets
      were assessed. In fish fed both soy diets, a significantly higher (P < 0.05) cell
      proliferation response was observed in the distal intestine concomitant with an
      increased localization of PCNA positive cells along the whole distal intestinal
      folds. The PCNA response among the nGM-soy group was significantly higher
      compared with all the other diet groups. In contrast, for fish exposed to dietary
      maize (type D) compared with fish fed the standard fishmeal, the soy-diets (GM
      soy and nGM-soy) and maize (type P), a significantly lower (P < 0.05) cell
      proliferation response was observed in the distal intestine. Results indicated
      that the GM plant products investigated in this study, at about 12% inclusion
      level, were as safe as commercially available non-GM products, at least in terms
      of their effect on indices and histological parameters of the Atlantic salmon
      intestinal tract.

PMID- 15960656
TI  - Polymorphisms in the sequences of Marteilia internal transcribed spacer region of
      the ribosomal RNA genes (ITS-1) in Spain: genetic types are not related with
      bivalve hosts.
AB  - Marteilia refringens is a protozoan parasite causing a disease notifiable to the
      Office International des Epizooties (OIE) and its distribution has implications
      for the transfer of live animals. The internal transcribed spacer-1 (ITS-1) from
      Marteilia clones contains polymorphism. Digestion with HhaI reveals two different
      restriction profiles, previously referred as 'O' (Marteilia from oyster or
      Marteilia refringens) and 'M' (Marteilia from mussels or Marteilia maurini). The
      aim of the present work was to determine whether the two previously described
      Marteilia molecular types (O and M) exist in the Iberian Peninsula and the
      strictness of the association with their bivalve host species. The sequence
      variability in the ITS-1 of Marteilia species was studied in mussels, Mytilus
      galloprovincialis, and flat oysters, Ostrea edulis, from different geographical
      locations in Spain, to establish the existence and the distribution of different
      species or molecular types. Although there were two distinct evolutionary
      lineages that corresponded more or less strictly with the 'M' and 'O' types, it
      was evident from the estimated phylogeny that some 'O' types have switched to 'M'
      type, and vice versa. Moreover, 'O' types were found in mussels and 'M' types
      were found in oysters, which suggests that there have been several cross-species
      transmissions of Marteilia between mussels and oysters.

PMID- 15960657
TI  - Nocardiosis in large yellow croaker, Larimichthys crocea (Richardson).
AB  - An epizootic in seawater-cage reared large yellow croaker, Larimichthys crocea,
      in China was caused by a Nocardia sp. from August to October 2003. The cumulative
      mortality rate was 15% and the diseased fish were 16 months old with individual
      length varying from 25 to 30 cm. Multiple, white nodules, 0.1-0.2 cm in diameter,
      were scattered on the heart, spleen and kidney. The morphology of isolated
      bacteria from Lowenstein-Jensen medium and tryptic soy agar was bead-like or
      long, slender, filamentous rods. Experimental infection indicated that the
      isolated bacterium was the pathogen responsible for the mortalities. A partial
      sequence of the 16S rRNA gene of the organism and the type strain of Nocardia
      seriolae JCM 3360T (Z36925) formed a monophyletic clade with a high sequence
      similarity of 99.9%. Based on the morphological, physiological, biological
      properties and the phylogenetic analysis, the pathogenic organism was identified
      as N. seriolae. This is the first report on N. seriolae-infected large yellow
      croaker in aquaculture.

PMID- 15960658
TI  - The effect of beta-glucan administration on macrophage respiratory burst activity
      and Atlantic salmon, Salmo salar L., challenged with amoebic gill disease-
      evidence of inherent resistance.
AB  - Previous studies have demonstrated that beta-glucans stimulate Atlantic salmon,
      Salmo salar L., head kidney macrophages both in vitro and in vivo and increase
      protection against various pathogens. Based on our previous work that showed
      potent immunostimulatory CpG motif-containing oligodeoxynucleotides increased
      resistance to amoebic gill disease (AGD), the present study investigated the
      immunostimulatory effects of three commercial beta-glucan-containing feeds and
      their ability to increase resistance to AGD. All three commercial beta-glucans
      were able to stimulate the respiratory burst activity of Atlantic salmon head
      kidney macrophages in vitro, albeit at different times and concentrations.
      However, dietary incorporation of the beta-glucans was unable to stimulate the in
      vivo respiratory burst activity of head kidney macrophages, or serum lysozyme
      production, and did not increase resistance against AGD. However, this trial
      showed for the first time that a small subpopulation of Atlantic salmon subjected
      to a severe AGD infection was able to resist becoming heavily infected and
      furthermore survive the challenge.

PMID- 15960659
TI  - Histidine nutrition and genotype affect cataract development in Atlantic salmon,
      Salmo salar L.
AB  - The aim of this study was to investigate effects of dietary levels of histidine
      (His) and iron (Fe) on cataract development in two strains of Atlantic salmon
      monitored through parr-smolt transformation. Three experimental diets were fed:
      (i) a control diet (CD) with 110 mg kg(-1) Fe and 11.7 g kg(-1) His; (ii) CD
      supplemented with crystalline His to a level of 18 g kg(-1) (HD); and (iii) HD
      with added iron up to 220 mg kg(-1) (HID). A cross-over design, with two feeding
      periods was used. A 6-week freshwater (FW) period was followed by a 20-week
      period, of which the first three were in FW and the following 17 weeks in sea
      water (SW). Fish were sampled for weighing, cataract assessment and tissue
      analysis at five time points. Cataracts developed in all groups in SW, but scores
      were lower in those fed high His diets (P < 0.05). This effect was most
      pronounced when HD or HID was given in SW, but was also observed when these diets
      were given in FW only. Histidine supplementation had a positive effect on growth
      performance and feed conversion ratio (P < 0.05), whereas this did not occur when
      iron was added. Groups fed HD or HID had higher lens levels of His and N-acetyl
      histidine (NAH), the latter showing a marked increase post-smoltification (P <
      0.05). The HD or HID groups also showed higher muscle concentrations of the His
      dipeptide anserine (P < 0.05). There was a strong genetic influence on cataract
      development in the CD groups (P < 0.001), not associated with tissue levels of
      His or NAH. The role of His and His-related compounds in cataractogenesis is
      discussed in relation to tissue buffering, osmoregulation and antioxidation.

PMID- 15960660
TI  - Longitudinal serological surveys of Atlantic salmon, Salmo salar L., using a
      rapid immunoperoxidase-based neutralization assay for salmonid alphavirus.
AB  - Longitudinal serological surveys for salmon pancreas disease virus (SPDV), the
      causal agent of pancreas disease (PD), were conducted on multiple caged
      populations of Atlantic salmon, Salmo salar L., on two farms over a 77-week
      period (farm 1, freshwater and marine stages) and a 36-week period (farm 2,
      marine stage only), using a microtitre-based virus neutralization (VN) assay.
      Collected sera were also screened for viraemia with SPDV, and pancreas, heart and
      muscle tissues were examined for lesions consistent with PD. Outbreaks of PD
      occurred during the marine phase on both farms, as demonstrated by
      seroconversion, the isolation of virus and progressive histopathological changes
      consistent with a PD outbreak. All populations monitored showed a progressive
      increase in seroprevalence of 90-100%, typically accompanied by rises in
      geometric mean antibody titres. With the exception of one caged population, which
      showed a marked biphasic seroprevalence pattern, the seroprevalence figures in
      the remaining four monitored populations remained high (> or =70%) until the end
      of the study period. Peak VN titres of > or =1/1280 were detected on both farms.
      The results provide essential baseline information for the interpretation of SPDV
      VN serology results, and indicate that this methodology is suited to both the
      diagnosis and seroepidemiology of SPDV infections.

PMID- 15960661
TI  - Human safety and genetically modified plants: a review of antibiotic resistance
      markers and future transformation selection technologies.

PMID- 15960662
TI  - Use of green fluorescent protein-based reporters to monitor balanced production
      of antifungal compounds in the biocontrol agent Pseudomonas fluorescens CHA0.
AB  - AIMS: To develop reporter constructs based on stable and unstable variants of the
      green fluorescent protein (GFP) for monitoring balanced production of antifungal
      compounds that are crucial for the capacity of the root-colonizing Pseudomonas
      fluorescens strain CHA0 to control plant diseases caused by soil-borne pathogenic
      fungi. METHODS AND RESULTS: Pseudomonas fluorescens CHA0 produces the three
      antifungal metabolites 2,4-diacetylphloroglucinol (DAPG), pyoluteorin (PLT) and
      pyrrolnitrin (PRN). The gfp[mut3] and gfp[AAV] reporter genes were fused to the
      promoter regions of the DAPG, PLT and PRN biosynthetic genes. The reporter
      fusions were then used to follow the kinetics of expression of the three
      antifungal metabolites in a microplate assay. DAPG and PLT were found to display
      an inverse relationship in which each metabolite activates its own biosynthesis
      while repressing the synthesis of the other metabolite. PRN appears not to be
      involved in this balance. However, the microbial and plant phenolic metabolite
      salicylate was found to interfere with the expression of both DAPG and PLT.
      CONCLUSIONS: The results obtained provide evidence that P. fluorescens CHA0 may
      keep the antifungal compounds DAPG and PLT at a fine-tuned balance that can be
      affected by certain microbial and plant phenolics. SIGNIFICANCE AND IMPACT OF THE
      STUDY: To our knowledge, the present study is the first to use stable and
      unstable GFP variants to study antibiotic gene expression in a biocontrol
      pseudomonad. The developed reporter fusions will be a highly valuable tool to
      study in situ expression of this bacterial biocontrol trait on plant roots, i.e.
      at the site of pathogen suppression.

PMID- 15960663
TI  - Oxygen and photoinactivation of Escherichia coli in UVA and sunlight.
AB  - AIMS: To establish the influence of oxygen on Escherichia coli before, during and
      after exposure to UVA or simulated sunlight. METHODS AND RESULTS: Bacterial
      suspensions were exposed either to UVA or simulated sunlight. Conventional
      aerobic plate counts of illuminated cell suspensions were consistently lower than
      those obtained under conditions where reactive oxygen species (ROS) were
      neutralized, either (i) by the addition of the peroxide scavenger sodium pyruvate
      (0.05% w/v) to the medium with subsequent incubation in an anaerobic jar or (ii)
      by culturing on a prereduced medium within an anaerobic cabinet, indicating that
      a substantial proportion of such cells are sublethally injured. While the
      presence of oxygen during the growth period resulted in a greater resistance of
      aerobically grown cells to simulated sunlight compared with their anaerobic
      counterparts, the extent of inactivation during illumination was directly related
      to the dissolved oxygen content of the water. CONCLUSIONS: The results show that,
      at each stage, oxygen has a marked influence on the observed colony count.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Overall, the results indicate that future
      studies of bacteria exposed to UVA or sunlight should consider the effects of
      oxygen at every stage in the procedure, and especially during enumeration, where
      the inhibitory effects of ROS must be neutralized in order to obtain a valid
      count. An investigation of the effects of ROS neutralization on the counts of
      faecal bacteria under field conditions in natural waters is now required to
      establish the significance of these finding to solar water treatment.

PMID- 15960664
TI  - Species-specific oligonucleotide probes for the detection and identification of
      Lactobacillus isolated from mouse faeces.
AB  - AIMS: To develop species-specific monitoring techniques for rapid detection and
      identification of Lactobacillus isolated from mouse faeces. METHODS AND RESULTS:
      The specificity of oligonucleotide probes was evaluated by dot blot hybridization
      to 16S rDNA and 23S rDNA amplified by PCR from 12 Lactobacillus type strains and
      100 strains of Lactobacillus isolated from mouse faeces. Oligonucleotide probes
      specific for each Lactobacillus species hybridized only with targeted rDNA. The
      Lactobacillus strains isolated from mouse faeces were identified mainly as
      Lactobacillus intestinalis, L. johnsonii, L. murinus and L. reuteri using species
      specific probes. 16S rDNA of eight unidentified isolates were sequenced and two
      new probes were designed. Four of eight strains of unhybridized Lactobacillus
      were identified as L. johnsonii/gasseri group, and the remaining four strains as
      L. vaginalis. CONCLUSIONS: The species-specific probe set of L. intestinalis, L.
      johnsonii, L. murinus, L. reuteri and L. vaginalis in this study was efficient
      for rapid identification of Lactobacillus isolated from mouse faeces.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The oligonucleotide probe set for
      Lactobacillus species harboured in the mouse intestine, can be used for rapid
      identification of lactobacilli and monitoring of the faecal Lactobacillus
      community.

PMID- 15960665
TI  - Declines of zoonotic agents in liquid livestock wastes stored in batches on-farm.
AB  - AIM: To measure the decline rates of zoonotic agents introduced into liquid
      livestock wastes in on-farm storage tanks. METHODS AND RESULTS: Salmonella spp.,
      Escherichia coli O157, Campylobacter jejuni, Listeria monocytogenes and
      Cryptosporidium parvum, propagated in laboratory-controlled conditions, were
      inoculated into 35,000-l volumes of fresh livestock wastes (pig slurries, cattle
      slurries and dirty waters). D-values for bacteria were six to 44 days, and for C.
      parvum were 133 to 345 days. Campylobacter jejuni declined significantly more
      rapidly than the other bacterial pathogens, while E. coli O157 declined
      significantly more slowly. On average, bacterial declines were not affected by
      the season of waste deposition and storage or by the dry matter content of the
      wastes, but were more rapid in dirty waters than in pig slurries. The
      physiciochemical composition of wastes in each category varied significantly.
      CONCLUSIONS: Zoonotic agents can survive for several months during storage of
      liquid livestock wastes. Livestock wastes should be batch-stored and not
      subjected to continuous additions. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study indicates that batches of liquid livestock waste, if contaminated with
      bacterial pathogens, should be stored for 6 months to reduce contamination
      levels. Alternative strategies for reducing C. parvum levels in liquid livestock
      wastes should be explored.

PMID- 15960666
TI  - Shelf life and safety aspects of chilled cooked and peeled shrimps (Pandalus
      borealis) in modified atmosphere packaging.
AB  - AIMS: To evaluate the growth of Listeria monocytogenes and shelf life of cooked
      and peeled shrimps in modified atmosphere packaging (MAP). METHODS AND RESULTS:
      Storage trials with naturally contaminated cooked and peeled MAP shrimps
      (Pandalus borealis) were carried out at 2, 5 and 8 degrees C. Challenge tests at
      the same conditions were performed after inoculation with Listeria monocytogenes.
      Both storage trials and challenge tests were repeated after 4 months of frozen
      storage (-22 degrees C). Brochothrix thermosphacta and Carnobacterium
      maltaromaticum were responsible for sensory spoilage of cooked and peeled MAP
      shrimps. In challenge tests, growth of L. monocytogenes was observed at all of
      the storage temperatures studied. At 5 and 8 degrees C the concentration of L.
      monocytogenes increased more than a 1000-fold before the product became sensory
      spoiled whereas this was not observed at 2 degrees C. Frozen storage had only a
      minor inhibiting effect on growth of L. monocytogenes in the thawed product.
      CONCLUSIONS: To prevent L. monocytogenes becoming a safety problem, cooked and
      peeled MAP shrimps should be distributed at 2 degrees C and with a maximum shelf
      life of 20-21 d. At higher temperatures shelf life is significantly reduced.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Information is provided to establish shelf
      life of cooked and peeled MAP shrimps.

PMID- 15960667
TI  - Antimicrobial activity of lactic acid bacteria isolated from Tenerife cheese:
      initial characterization of plantaricin TF711, a bacteriocin-like substance
      produced by Lactobacillus plantarum TF711.
AB  - AIMS: The screening and initial characterization of bacteriocins produced by
      lactic acid bacteria (LAB) from raw Tenerife goats' cheese with possible
      application as biopreservatives or ripening accelerators for Tenerife cheese.
      METHODS AND RESULTS: One hundred and eighty LAB of the genera Lactobacillus (95),
      Leuconostoc (64) and Lactococcus (21) isolated from raw Tenerife goats' cheese
      were screened for the production of antimicrobial substances. Lactobacillus
      plantarum TF711, which had the broadest spectrum of antimicrobial activity, was
      selected for further characterization. The antimicrobial compound was determined
      as a proteinaceous substance, as it was sensitive to proteases. The bacteriocin
      like substance, which we called plantaricin TF711, was active against the Gram
      positive bacteria Bacillus cereus, Clostridium sporogenes and Staphylococcus
      aureus; and against the Enterobacteriaceae Shigella sonnei and Klebsiella
      pneumoniae. It was stable to heat and to treatment with surfactants and organic
      solvents. Highest antimicrobial activity was found between pH 1 and 9.
      Plantaricin TF711 exhibited primary metabolite kinetics, a bacteriostatic mode of
      action and a molecular mass of c. 2.5 kDa as determined by tricine SDS-PAGE.
      CONCLUSIONS: Lact. plantarum TF711 produces a low molecular mass bacteriocin-like
      compound with a wide spectrum of activity and interesting technological
      properties (thermostability, good pH stability and stability against surfactants
      and organic solvents). SIGNIFICANCE AND IMPACT OF THE STUDY: Plantaricin TF711
      was found to have potential for use as a biopreservative in the food industry.

PMID- 15960668
TI  - Evidence for viable but nonculturable yeasts in botrytis-affected wine.
AB  - AIMS: In Botrytis-affected wine, high concentrations of SO2 are added to stop the
      alcoholic fermentation and to stabilize the wine. During maturing in barrels or
      bottle-ageing, an unwanted refermentation can sometimes occur. However, results
      of the usual plate count of wine samples at the beginning of maturing suggest
      wine microbial stability. The aim of this study was to investigate the mode of
      yeasts survival after the addition of SO2 and to identify surviving yeasts.
      METHODS AND RESULTS: Using direct epifluorescence technique, we observed the
      behaviour of cells after SO2 addition and compared the cell number determined by
      this method with the result of plate counts. The persistent yeast species were
      identified using two methods: polymerase chain reaction (PCR)-restriction
      fragment length polymorphism and PCR-denaturing gradient gel electrophoresis.
      They were identified as Saccharomyces cerevisiae and Candida stellata, and after
      few months of maturing, other spoiling yeasts appeared, like Rhodotorula
      mucilaginosa or Zygosaccharomyces bailii. CONCLUSIONS: All characteristics of the
      cells lead to the conclusion that yeast persisted in wine in a viable but
      nonculturable-like state (VBNC). Suppression of the effect of free-SO2 did not
      lead to the resuscitation of the cells; however, another method proved the
      capacity of the cells to exit from the VBNC-like state. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This study permits the characterization of the presence of VBNC
      like yeasts in wine. The 'refermentation' phenomenon is probably due to the exit
      of the VBNC state.

PMID- 15960669
TI  - Occurrence of sublethal injury after pulsed electric fields depending on the
      micro-organism, the treatment medium ph and the intensity of the treatment
      investigated.
AB  - AIMS: The objective was to investigate the occurrence of sublethal injury after
      pulsed electric field (PEF) depending on the treatment time, the electric field
      strength and the pH of the treatment media in two Gram-positive (Bacillus
      subtilis ssp. niger, Listeria monocytogenes) and six Gram-negative (Escherichia
      coli, Escherichia coli O157:H7, Pseudomonas aeruginosa, Salmonella serotype
      Senftenberg 775W, Salmonella serotype Typhimurium, Yersinia enterocolitica)
      bacterial strains. METHODS AND RESULTS: A characteristic behaviour was observed
      for the Gram-positive and Gram-negative bacteria studied. Whereas Gram-positive
      bacteria showed a higher PEF resistance at pH 7.0, the Gram-negative were more
      resistant at pH 4.0. In these conditions, in which bacteria showed their maximum
      resistance, a large proportion of sublethally injured cells were detected. In
      most cases, the longer the treatment time and the higher the electric field
      applied, the greater the proportion of sublethally injured cells that were
      detected. No sublethal injury was detected when Gram-positive bacteria were
      treated at pH 4.0 and Gram-negative at pH 7.0. CONCLUSIONS: Sublethal injury was
      detected after PEF so, bacterial inactivation by PEF is not an 'all or nothing'
      event. SIGNIFICANCE AND IMPACT OF THE STUDY: This work could be useful for
      improving food preservation by PEF.

PMID- 15960670
TI  - Interactions between Saccharomyces cerevisiae and malolactic bacteria:
      preliminary characterization of a yeast proteinaceous compound(s) active against
      Oenococcus oeni.
AB  - AIMS: To investigate the occurrence and extent of Saccharomyces cerevisiae and
      Oenococcus oeni interactions. METHODS AND RESULTS: Interactions between S.
      cerevisiae and O. oeni were investigated by double-layer and well-plate assays
      showing the occurrence of specific interactions for each yeast-malolactic
      bacteria (MLB) coupling. Heat and protease treatments of synthetic grape juice
      fermented by the S. cerevisiae strain F63 indicated that the inhibitory activity
      exerted by this yeast on O. oeni is due to a proteinaceous factor(s) which exerts
      either bacteriostatic or bactericidal effect depending on concentration and
      affects malolactic fermentation in natural grape juice and wine. CONCLUSIONS: A
      proteinaceous factor(s) produced by a S. cerevisiae wine strain able to inhibit
      O. oeni growth and malic acid fermentation was characterized. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The individuation, characterization and exploitation of
      yeast proteinaceous factor(s) exerting inhibitory activity on MLB may offer new
      opportunities for the management of malolactic fermentation.

PMID- 15960671
TI  - Upregulation of ALD3 and GPD1 in Saccharomyces cerevisiae during Icewine
      fermentation.
AB  - AIMS: To determine acetic acid, acetaldehyde and glycerol production by wine
      yeast throughout Icewine fermentation. The expression of yeast cytosolic aldehyde
      dehydrogenases (ALD3 and ALD6) and glycerol-3-phosphate dehydrogenase (GPD1) were
      followed to relate metabolites in the wines to expression patterns of these
      genes. METHODS AND RESULTS: Icewine juice (38.8 degrees Brix, 401 +/- 7 g l(-1)
      sugar), diluted Icewine juice (21.3 degrees Brix, 211 +/- 7 g l(-1) sugar) and
      the diluted juice with sugar levels equal to the original Icewine juice (35.6
      degrees Brix, 402 +/- 6 g l(-1) sugar) were fermented in triplicate using the
      commercial wine yeast K1-V1116. Acetic acid production increased 7.1-fold and
      glycerol production increased 1.8-fold in the Icewine fermentation over that
      found in the diluted juice fermentation. ALD3 showed a 6.2-fold induction and
      GPD1 showed a 2.5-fold induction during Icewine vs the diluted fermentation. ALD3
      was not glucose repressed when additional sugar was added to diluted juice, but
      was upregulated 7.0-fold. CONCLUSIONS: The NAD+-dependant aldehyde dehydrogenase
      encoded by ALD3 appears to contribute to acetic acid production during Icewine
      fermentation. Expression of GPD1 was upregulated in high sugar fermentations and
      reflects the elevated levels of glycerol. Solutes in Icewine juice in addition to
      sugar contribute to the yeast metabolic response. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This work represents the first descriptive analysis of the fermentation of
      Canadian Icewine, the expression patterns of yeast genes involved in metabolite
      production, and their impact on Icewine quality. A role for ALD3 in acetic acid
      production during Icewine fermentation was found.

PMID- 15960672
TI  - Overland flow delivery of faecal bacteria to a headwater pastoral stream.
AB  - AIMS: To quantify and derive statistical relationships with which to predict the
      delivery of faecal bacteria (Escherichia coli) to a pastoral stream, by overland
      flow. METHODS AND RESULTS: A large-scale (1050 m2) rainfall simulator, located
      upon a steep (18 degrees) grazed hillside in New Zealand, was used to simulate 11
      heavy rainfall events. Overland flow was generated and sampled throughout each
      event, before discharging to a headwater stream. The samples were subsequently
      analysed to determine the concentration of E. coli. Statistical analysis showed
      that the time elapsed since the last period of grazing was a statistically
      significant predictor of both the total number (load) and concentrations of E.
      coli in overland flow. Between 10(5) and 10(8)E. coli per m2 of hillside were
      delivered to the stream within overland flow during each event, and peak
      concentrations ranged between 10(3) and 10(7) most probable number per 100 ml.
      CONCLUSIONS: Under heavy rainfall on steep pastoral land, overland flow can
      transport substantial levels of faecal bacteria to streams. Under such
      conditions, it is unlikely that vegetated buffer strips will be particularly
      effective at attenuating bacteria within overland flow. SIGNIFICANCE AND IMPACT
      OF THE STUDY: This work has improved understanding of the importance of overland
      flow as a process contributing to the contamination of pastoral streams by faecal
      bacteria. In addition, the predictive relationships derived can be incorporated
      within catchment models.

PMID- 15960673
TI  - Antimicrobial susceptibility and pulsed-field gel electrophoresis of Shigella
      sonnei strains in Malaysia (1997-2000).
AB  - AIMS: Antimicrobial resistance of Shigella sonnei from Malaysia was determined
      and subtyping was carried by pulsed-field gel electrophoresis (PFGE) to assess
      the extent of genetic diversity of these strains. METHODS AND RESULTS: A total of
      62 isolates of S. sonnei from sporadic cases of shigellosis in different parts of
      Malaysia were studied by antimicrobial susceptibility test and PFGE.
      Approximately 35.5% of the strains showed resistance to three or more
      antimicrobial agents. Eight resistant phenotypes, i.e. RI to RVIII, was defined.
      Resistant phenotype RV and RVIII only appeared in year 2000. PFGE analysis with
      NotI and XbaI restriction showed that a great heterogeneity existed at the DNA
      level among Malaysian S. sonnei isolates. Fifty-eight NotI and 61 XbaI-PFGE
      profiles were observed in 63 S. sonnei isolates, including ATCC 11060 isolate.
      Drug sensitive isolates displayed very different profiles from drug-resistant
      isolates, with a few exceptions. Isolates of resistant phenotype RVI
      (SXTr.TETr.STRr) showed a greater similarity among each other compared with
      isolates of resistant phenotype RI and drug-sensitive isolates. CONCLUSION: Multi
      drug-resistant S. sonnei were circulated in different parts of Malaysia and the
      emergence of new resistant phenotype was observed. Wide genetic variations among
      Malaysian S. sonnei were observed and the drug-sensitive strains could be
      differentiated from drug-resistant strains by PFGE. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The present study verifies the usefulness of PFGE in characterizing
      and comparing strains of S. sonnei. Minor variations among S. sonnei isolates
      could be detected by PFGE.

PMID- 15960674
TI  - Enterococcus faecium F58, a bacteriocinogenic strain naturally occurring in Jben,
      a soft, farmhouse goat's cheese made in Morocco.
AB  - AIMS: Characterization of Ent F-58 produced by Enterococcus faecium strain F58
      isolated from Jben, a soft, farmhouse goat's cheese manufactured without starter
      cultures. METHODS AND RESULTS: E. faecium strain F58 was isolated because of its
      broad inhibitory spectrum, including activity against food-borne pathogenic and
      spoilage bacteria. The antimicrobial substance was produced during the growth
      phase, with maximum production after 16-20 h of incubation at 30 degrees C, and
      was stable over a wide pH range (4-8) and at high temperatures (5 min at 100
      degrees C). The enterocin was purified to homogeneity using cation exchange and
      hydrophobic interaction on C-18 and reverse-phase high-performance liquid
      chromatography. The activity was eluted as two individual active fractions (F-58A
      and F-58B) and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry analysis showed masses of 5210.5 and 5234.3 Da respectively. Both
      peptides were partially sequenced by Edman degradation, and amino-acid sequencing
      revealed high similarity with enterocin L50 (I). PCR-amplified fragments
      containing the structural genes for F-58 A and B were located in a 22-kb plasmid
      harboured by this strain. We verified that it also holds the structural gene for
      P-like enterocin. CONCLUSION: E. faecium strain F58 from Jben cheese, a producer
      of enterocin L50, exerts an inhibitory effect against strains of genera such as
      Listeria, Staphylococcus, Clostridium, Brochothrix and Bacillus. Enterocin was
      characterized according to its functional and biological properties, purification
      to homogeneity and an analysis of its amino acid and genetic sequences.
      SIGNIFICANCE AND IMPACT OF THE STUDY: E. faecium strain F58 is a newly discovered
      producer of enterocin L50, the biotechnological characteristics of which indicate
      its potential for application as a protective agent against pathogens and
      spoilage bacteria in foods.

PMID- 15960675
TI  - Poly(beta-hydroxybutyrate) production by a moderate halophile, Halomonas
      boliviensis LC1 using starch hydrolysate as substrate.
AB  - AIM: The objective of the present work was to enable the use of starch
      hydrolysate, generated by the action of a recombinant maltooligosaccharide
      forming amylase from Bacillus halodurans LBK 34, as the carbon source for the
      production of poly-beta-hydroxybutyrate (PHB) by Halomonas boliviensis LC1.
      METHODS AND RESULTS: In this work, different amounts of the alpha-amylase (Amy
      34) were utilized for starch hydrolysis, resulting in the production of mixtures
      of maltooligosaccharides (G1-G6) at varying ratios. The highest PHB accumulation
      (56 wt%) by H. boliviensis cultivated in shake flasks (with agitation at 160 rev
      min(-1)) was obtained when 6.4 U ml(-1) of the amylase was used for starch
      hydrolysis. When H. boliviensis cells were grown in a fermentor with no oxygen
      limitation the accumulation of PHB was decreased to 35 wt%. Although some
      improvements in PHB accumulation and cell mass concentration were reached by the
      addition of peptone and phosphate, respectively, major enhancements were attained
      when oxygen limitation was induced in the fermentor. CONCLUSIONS: Halomonas
      boliviensis uses preferentially maltose for PHB formation from starch
      hydrolysate. It is also able to hydrolyse higher sugars if no other simpler
      carbon source is available but with a significantly lower polymer yield.
      Furthermore, H. boliviensis is able to adjust its metabolism to oxygen
      limitation, most probably by directing the excess NAD(P)H to PHB accumulation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: There have been no reports related to PHB
      production amongst the members of the genus Halomonas. The use of a
      maltooligosaccharide forming alpha-amylase, which is active at a temperature and
      pH close to that required for growth of H. boliviensis, and the versatility of
      this bacterium in the selection of the carbon source may provide an attractive
      alternative for the utilization of starch-derived raw materials.

PMID- 15960676
TI  - Enterotoxigenic Staphylococcus aureus in bulk milk in Norway.
AB  - AIMS: To investigate the presence of enterotoxigenic Staphylococcus aureus in
      bulk milk and in a selection of raw milk products. METHODS AND RESULTS: Samples
      of bovine (n = 220) and caprine (n = 213) bulk milk, and raw milk products (n =
      82) were analysed for S. aureus. Isolates were tested for staphylococcal
      enterotoxin (SE) production (SEA-SED) by reversed passive latex agglutination and
      for SE genes (sea-see, seg-sej) by multiplex PCR. Staphylococcus aureus was
      detected in 165 (75%) bovine and 205 (96.2%) caprine bulk milk samples and in 31
      (37.8%) raw milk product samples. Enterotoxin production was observed in 22.1%
      and 57.3% of S. aureus isolates from bovine and caprine bulk milk, respectively,
      while SE genes were detected in 52.5% of the bovine and 55.8% of the caprine bulk
      milk isolates. SEC and sec were most commonly detected. A greater diversity of SE
      genes were observed in bovine vs caprine isolates. CONCLUSIONS: Staphylococcus
      aureus seems highly prevalent in Norwegian bulk milk and isolates frequently
      produce SEs and contain SE genes. Enterotoxigenic S. aureus were also found in
      raw milk products. SIGNIFICANCE AND IMPACT OF THE STUDY: Staphylococcus aureus in
      Norwegian bovine and caprine bulk milk may constitute a risk with respect to
      staphylococcal food poisoning from raw milk products.

PMID- 15960677
TI  - Optimization of technical conditions for the transformation of Lactobacillus
      acidophilus strains by electroporation.
AB  - AIMS: To optimize the conditions for electroporating foreign plasmid DNA into
      Lactobacillus acidophilus ATCC 43121. METHODS AND RESULTS: The conditions of
      electroporation were optimized to improve the transformation efficiency. Plasmid
      pNZ123 containing multicloning site and chloramphenicol resistance was employed
      to construct a cloning vector. The optimum electroporation conditions for the
      maximum transformation efficiency were a pulse strength of 12.5 kV cm(-1), a
      pulse number of 10, a pulse interval of 500 ms, and pNZ123 plasmid DNA
      concentration of 25 ng microl(-1). Under the optimum conditions the
      transformation efficiency of L. acidophilus ATCC 43121 was 1.84 +/- 0.13 x 10(4)
      (+/- standard error of measurements) CFU per mug of plasmid DNA. Other strains of
      L. acidophilus showed transformation efficiencies ranging from 1.38 +/- 0.02 x
      10(4) to 9.32 +/- 0.54 x 10(4) under these conditions. A green fluorescent
      protein (GFP) was successfully expressed and detected by fluorescence microscopy
      when the pKU::slpA-GFP, pNZ123 containing GFP gene, was transformed in L.
      acidophilus ATCC 43121 under the optimum conditions. CONCLUSIONS: The results
      suggest that electrical parameters, antibiotic concentration, and host
      specificity play important roles to determine transformation efficiency of
      lactobacilli. The optimum conditions for the transformation of L. acidophilus
      ATCC 43121 may be applied to improve transformation efficiency of other
      lactobacilli. SIGNIFICANCE AND IMPACT OF THE STUDY: The optimized conditions for
      electrotransformation may provide a mean to improve the introduction of foreign
      DNA into L. acidophilus to be used as a vehicle for a heterologous protein
      expression.

PMID- 15960678
TI  - Profiling bacterial survival through a water treatment process and subsequent
      distribution system.
AB  - AIMS: To profile fractions of active bacteria and of bacteria culturable with
      routine heterotrophic plate count (HPC) methods through a typical water treatment
      process and subsequent distribution system. In doing so, investigate how water
      treatment affects both bacterial abundance and diversity, and reveal the
      identities of active bacteria not detected by traditional HPC culture. METHODS
      AND RESULTS: Profiling active fractions was performed by flow cytometric cell
      sorting of either membrane-intact (BacLight kit) or enzymatically active
      (carboxyfluorescein diacetate, CFDA) bacteria, followed by eubacterial 16S rDNA
      directed PCR and denaturing gradient gel electrophoresis (DGGE). Water treatment
      significantly reduced active bacterial numbers detected by the BacLight kit and
      CFDA assay by 2.89 and 2.81 log respectively. Bacterial diversity was also
      reduced from > 20 DGGE bands in the active fractions of reservoir water to only
      two bands in the active fractions of finished water. These two bands represented
      Stenotrophomonas maltophila, initially culturable by HPC, and a Burkholderia
      related species. Both species maintained measurable traits of physiological
      activity in distribution system bulk water but were undetected by HPC.
      CONCLUSIONS: Flow cytometric cell sorting with PCR-DGGE, to assess water
      treatment efficacy, identified active bacteria from a variety of major
      phylogenetic groups undetected by routine HPC. Following treatment S. maltophila
      and a Burkholderia-related species retained activity and entered distribution
      undetected by HPC. SIGNIFICANCE AND IMPACT OF THE STUDY: Methods used here
      demonstrate how water treatment operators can better monitor water treatment
      plant efficacy and assess distribution system instability by the detection and
      identification of active bacteria recalcitrant to routine HPC culture.

PMID- 15960679
TI  - Estimating non-isothermal bacterial growth in foods from isothermal experimental
      data.
AB  - AIM: To develop a mathematical method to estimate non-isothermal microbial growth
      curves in foods from experiments performed under isothermal conditions and
      demonstrate the method's applicability with published growth data. METHODS AND
      RESULTS: Published isothermal growth curves of Pseudomonas spp. in refrigerated
      fish at 0-8 degrees C and Escherichia coli 1952 in a nutritional broth at 27.6-36
      degrees C were fitted with two different three-parameter 'primary models' and the
      temperature dependence of their parameters was fitted by ad hoc empirical
      'secondary models'. These were used to generate non-isothermal growth curves by
      solving, numerically, a differential equation derived on the premise that the
      momentary non-isothermal growth rate is the isothermal rate at the momentary
      temperature, at a time that corresponds to the momentary growth level of the
      population. The predicted non-isothermal growth curves were in agreement with the
      reported experimental ones and, as expected, the quality of the predictions did
      not depend on the 'primary model' chosen for the calculation. CONCLUSIONS: A
      common type of sigmoid growth curve can be adequately described by three
      parameter 'primary models'. At least in the two systems examined, these could be
      used to predict growth patterns under a variety of continuous and discontinuous
      non-isothermal temperature profiles. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      described mathematical method whenever validated experimentally will enable the
      simulation of the microbial quality of stored and transported foods under a large
      variety of existing or contemplated commercial temperature histories.

PMID- 15960680
TI  - Lactate is mainly fermented to butyrate by human intestinal microfloras but inter
      individual variation is evident.
AB  - AIM: To assess the role of lactate as a precursor for butyrate biosynthesis in
      human colonic microflora. METHODS AND RESULTS: Three human faecal microfloras
      were incubated in vitro with media supplemented with 30 mmol l(-1) unenriched or
      13C-enriched lactate. Lactate metabolism and short-chain fatty acid (SCFA)
      production were quantified. Lactate conversion to butyrate was investigated by
      gas chromatography-mass spectrometry and the pathways involved were identified by
      13C nuclear magnetic resonance spectroscopy. All human faecal microfloras rapidly
      and completely fermented lactate, yielding approx. 19 mmol l(-1) total SCFAs.
      However, the SCFA composition varied markedly between microfloras. Butyrate was
      the main end-product for two microfloras but not for the third (60 and 61%vs 27%
      of the net concentration of SCFA produced respectively). The latter was typified
      by its ability to produce propionate as a major product (37%), and valerate (3%).
      13C-Labelling showed that butyrate was produced through the acetyl-CoA pathway
      and that the three microfloras possessed significant differences in their
      metabolic pathways for lactate consumption. CONCLUSIONS: In contrast to the
      ruminal microflora, the human intestinal microflora can utilize both d- and l
      lactate as precursors for butyrate synthesis. Inter-individual variation is
      found. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the
      butyrogenic capability of colonic prebiotics could be related to lactate
      availability. These findings will direct the development of selection strategies
      for the isolation of new butyrate-producing bacteria among the lactate-utilizing
      bacteria present in the human intestinal microfloras.

PMID- 15960681
TI  - Biological control agent of common scab disease by antagonistic strain Bacillus
      sp. sunhua.
AB  - AIMS: To identify an antagonistic strain against Streptomyces scabiei and to
      characterize the antibiotic agent. The efficacy of the isolated strain in
      controlling common scab disease was also evaluated. METHODS AND RESULTS: A
      bacterial strain antagonistic against S. scabiei was isolated from the soil of a
      potato-cultivating area. This bacterium was identified as a Bacillus species by
      16S rRNA gene sequence analysis and was designated Bacillus sp. sunhua.
      Antibiotics produced by this strain were proven to be stable within a broad pH
      range and at high temperatures. The culture broth was extracted with ethyl
      acetate, and then the crude extract was applied to HPLC. Two compounds were
      isolated and identified as iturin A and macrolactin A by 1H-NMR, 13C-NMR, HMBC,
      HMQC and mass spectrometer. The culture broth of Bacillus sp. sunhua had a
      suppressive effect on common scab disease in a pot assay, decreasing the
      infection rate from 75 to 35%. This strain also suppressed Fusarium oxysporum,
      the pathogen of potato dry rot disease. CONCLUSIONS: Bacillus sp. sunhua was
      shown to inhibit S. scabiei effectively. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This is the first report demonstrating that macrolactin A and iturin A inhibit S.
      scabiei. This study demonstrated the possibility of controlling potato scab
      disease using Bacillus sp. sunhua.

PMID- 15960682
TI  - Health care reform and health services research: what once was old is new again,
      and again.

PMID- 15960683
TI  - Profit-seeking, corporate control, and the trustworthiness of health care
      organizations: assessments of health plan performance by their affiliated
      physicians.
AB  - OBJECTIVE: To compare the relative trustworthiness of nonprofit and for-profit
      health plans, using physician assessments to measure dimensions of plan
      performance that are difficult for consumers to evaluate. DATA SOURCE: A
      nationally representative sample of 1,621 physicians who responded to a special
      topics module of the 1998 Socioeconomic Monitoring System Survey (SMS), fielded
      by the American Medical Association. Physicians assessed various aspects of their
      primary managed care plan, defined as the plan in which they had the largest
      number of patients. STUDY DESIGN: Plan ownership was measured as the interaction
      of tax-exempt status (nonprofit versus for-profit) and corporate control (single
      state versus multistate health plans). Two sets of regression models are
      estimated. The dependent variables in the regressions are five measures of
      performance related to plan trustworthiness: two related to deceptive practices
      and three to dimensions of quality that are largely hidden from enrollees. The
      first set (baseline) models relate plan ownership to trustworthy practices,
      controlling for other characteristics of the plan, the marketplace for health
      insurance, and the physician respondents. The second (interactive) set of models
      examines how the magnitude of ownership-related differences in trustworthiness
      varies with the market share of nonprofit plans in each community. DATA
      COLLECTION: The 1998 SMS was fielded between April and September of 1998 by
      Westat Inc. The average time required for a completed interview was approximately
      30 minutes. The overall response rate was 52.2 percent. PRINCIPAL FINDINGS:
      Compared with more local nonprofit plans, for-profit plans affiliated with
      multistate corporations are consistently reported by their affiliated physicians
      to engage in practices associated with reduced trustworthiness. Nonprofit plans
      affiliated with multistate corporations have more physician-reported practices
      associated with trustworthiness than do for-profit corporate plans on four of
      five outcomes, but appear less trustworthy than locally controlled nonprofits on
      two of the five measures. The magnitude of these ownership-related differences
      declines as the market share of nonprofit plans rises: for two of the five
      measures, ownership-related differences in practices related to trustworthiness
      are entirely eliminated when the nonprofits enroll more than 30 percent of the
      local market. CONCLUSIONS: The combination of for-profit ownership and multistate
      corporate control appears to consistently and substantially reduce physician
      reported measures related to the trustworthiness of health plans. Because this is
      the fastest growing form of managed care, these results raise concerns about
      further erosion of trust in American health care. Preserving a substantial market
      niche for nonprofit plans appears to reduce this erosion and should be considered
      by policymakers as a strategy for restoring trust in the health care system.

PMID- 15960685
TI  - Commentary--assessing the impact of managed care patient protection laws:
      problems and pitfalls.

PMID- 15960684
TI  - Impacts of managed care patient protection laws on health services utilization
      and patient satisfaction with care.
AB  - OBJECTIVE: To assess effects of patient protection laws implemented by the vast
      majority of states during the 1990s on the public's satisfaction and trust
      relating to health care, and on key utilization measures. DATA SOURCES/STUDY
      SETTING: Measures of individuals' health care utilization and satisfaction, and
      control variables, came from three waves of the Community Tracking Study (CTS)
      Household Surveys conducted in 1996-1997, 1998-1999, and 2000-2001. The CTS was
      conducted in 60 randomly selected communities, throughout the U.S. In addition, a
      supplemental national sample of households from CTS was also included, resulting
      in a combined sample with cases from 48 states and the District of Columbia.
      After applying exclusion restrictions, the analysis sample was 149,688 adults.
      STUDY DESIGN: Using a fixed-effects methodology, we assessed the influence of
      patient protection laws on satisfaction with care and utilization of services for
      the entire sample and for subsamples of persons in poor health, with low income,
      and who were enrolled in HMOs. DATA COLLECTION/EXTRACTION METHODS: One of the
      authors (Hall) compiled relevant laws in all U.S. states through 2001 from
      primary legal sources, checking for accuracy by conducting independent research
      on statutory changes and by asking three to five regulators in each state to
      verify that the information was correct. PRINCIPAL FINDINGS: Overall, patient
      protection laws had little or no effect on either trust, satisfaction with care,
      or utilization. Significance was found postenactment of a state patient
      protection law only for emergency room visits in the general sample, and only for
      physician trust in the low-income sample. Because of the number of possible
      associations examined, occasional findings of significance could occur by chance.
      CONCLUSIONS: Enactment of managed care patient protection laws did not generally
      increase utilization of health services or improve patient satisfaction with
      care.

PMID- 15960686
TI  - Characteristics of medical practices in three developed managed care markets.
AB  - OBJECTIVE: To describe physician practices, ranging from solo and two-physician
      practices to large medical groups, in three geographically diverse parts of the
      country with strong managed care presences. DATA SOURCES/STUDY DESIGN: Surveys of
      medical practices in three managed care markets conducted in 2000-2001. STUDY
      DESIGN: We administered questionnaires to all medical practices affiliated with
      two large health plans in Boston, MA, and Portland, OR, and to all practices
      providing primary care for cardiovascular disease patients admitted to five large
      hospitals in Minneapolis, MN. We offer data on how physician practices are
      structured under managed care in these geographically diverse regions of the
      country with a focus on the structural characteristics, financial arrangements,
      and care management strategies adopted by practices. DATA COLLECTION: A two
      staged survey consisting of an initial telephone survey that was undertaken using
      CATI (computerized assisted telephone interviewing) techniques followed by
      written modules triggered by specific responses to the telephone survey.
      PRINCIPAL FINDINGS: We interviewed 468 practices encompassing 668 distinct sites
      of care (overall response rate 72 percent). Practices had an average of 13.9
      member physicians (range: 1-125). Most (80.1 percent) medium- (four to nine
      physicians) and large-size (10 or more physicians) groups regularly scheduled
      meetings to discuss resource utilization and referrals. Almost 90 percent of the
      practices reported that these meetings occurred at least once per month. The
      predominant method for paying practices was via fee-for-service payments. Most
      other payments were in the form of capitation. Overall, 75 percent of physician
      practices compensated physicians based on productivity, but there was substantial
      variation related to practice size. Nonetheless, of the practices that did not
      use straight productivity methods (45 percent of medium-sized practices and 54
      percent of large practices), most used arrangements consisting of combinations of
      salary and productivity formulas. CONCLUSIONS: We found diversity in the
      characteristics and capabilities of medical practices in these three markets with
      high managed care involvement. Financial practices of most practices are geared
      towards rewarding productivity, and care management practices and capabilities
      such as electronic medical records remain underdeveloped.

PMID- 15960687
TI  - Welfare reform and health insurance of immigrants.
AB  - OBJECTIVE: To investigate the effect of the Personal Responsibility and Work
      Opportunity Reconciliation Act (PRWORA) on the health insurance coverage of
      foreign- and U.S.-born families headed by low-educated women. DATA SOURCE:
      Secondary data from the March series of the Current Population Surveys for 1994
      2001. STUDY DESIGN: Multivariate regression methods and a pre- and post-test with
      comparison group research design (difference-in-differences) are used to estimate
      the effect of welfare reform on the health insurance coverage of low-educated,
      foreign- and U.S.-born unmarried women and their children. Heterogeneous
      responses by states to create substitute Temporary Aid to Needy Families or
      Medicaid programs for newly arrived immigrants are used to investigate whether
      the estimated effect of PRWORA on newly arrived immigrants is related to the
      actual provisions of the law, or the result of fears engendered by the law.
      PRINCIPAL FINDINGS: PRWORA increased the proportion of uninsured among low
      educated, foreign-born, unmarried women by 9.9-10.7 percentage points. In
      contrast, the effect of PRWORA on the health insurance coverage of similar U.S.
      born women is negligible. PRWORA also increased the proportion of uninsured among
      foreign-born children living with low-educated, single mothers by 13.5 percentage
      points. Again, the policy had little effect on the health insurance coverage of
      the children of U.S.-born, low-educated single mothers. There is some evidence
      that the fear and uncertainty engendered by the law had an effect on immigrant
      health insurance coverage. CONCLUSIONS: This research demonstrates that PRWORA
      adversely affected the health insurance of low-educated, unmarried, immigrant
      women and their children. In the case of unmarried women, it may be partly
      because the jobs that they obtained in response to PRWORA were less likely to
      provide health insurance. The research also suggests that PRWORA may have
      engendered fear among immigrants and dampened their enrollment in safety net
      programs.

PMID- 15960688
TI  - The effect of Medicaid payment generosity on access and use among beneficiaries.
AB  - OBJECTIVE: This study examines the effects of Medicaid payment generosity on
      access and care for adult and child Medicaid beneficiaries. DATA SOURCE: Three
      years of the National Surveys of America's Families (1997, 1999, 2002) are linked
      to the Urban Institute Medicaid capitation rate surveys, the Area Resource File,
      and the American Hospital Association survey files. STUDY DESIGN: In order to
      identify the effect of payment generosity apart from unmeasured differences
      across areas, we compare the experiences of Medicaid beneficiaries with groups
      that should not be affected by Medicaid payment policies. To assure that these
      groups are comparable to Medicaid beneficiaries, we reweight the data using
      propensity score methods. We use a difference-in-differences model to assess the
      effects of Medicaid payment generosity on four categories of access and use
      measures (continuity of care, preventive care, visits, and perceptions of
      provider communication and quality of care). PRINCIPAL FINDINGS: Higher payments
      increase the probability of having a usual source of care and the probability of
      having at least one visit to a doctor and other health professional for Medicaid
      adults, and produce more positive assessments of the health care received by
      adults and children. However, payment generosity has no effect on the other
      measures that we examined, such as the probability of receiving preventive care
      or the probability of having unmet needs. CONCLUSIONS: Higher payment rates can
      improve some aspects of access and use for Medicaid beneficiaries, but the
      effects are not dramatic.

PMID- 15960689
TI  - Satisfaction with surgery outcomes and the decision process in a population-based
      sample of women with breast cancer.
AB  - OBJECTIVE: To better understand medical decision making in the context of
      "preference sensitive care," we investigated factors associated with breast
      cancer patients' satisfaction with the type of surgery received and with the
      decision process. DATA SOURCES/DATA COLLECTION: For a population-based sample of
      recently diagnosed breast cancer patients in the Detroit and Los Angeles
      metropolitan areas (N=1,633), demographic and clinical data were obtained from
      the Surveillance, Epidemiology, and End Results tumor registry, and self-reported
      psychosocial and satisfaction data were obtained through a mailed survey (78.4
      percent response rate). STUDY DESIGN: Cross-sectional design in which
      multivariable logistic regression was used to identify sociodemographic and
      clinical factors associated with three satisfaction measures: low satisfaction
      with surgery type, low satisfaction with the decision process, and decision
      regret. PRINCIPAL FINDINGS: Overall, there were high levels of satisfaction with
      both surgery and the decision process, and low rates of decision regret. Ethnic
      minority women and those with low incomes were more likely to have low
      satisfaction or decision regret. In addition, the match between patient
      preferences regarding decision involvement and their actual level of involvement
      was a strong indicator of satisfaction and decision regret/ambivalence. While
      having less involvement than preferred was a significant indicator of low
      satisfaction and regret, having more involvement than preferred was also a risk
      factor. Women who received mastectomy without reconstruction were more likely to
      report low satisfaction with surgery (odds ratio [OR]=1.54, p<.05), low
      satisfaction with the process (OR=1.37, p<.05), and decision regret (OR=1.55,
      p<.05) compared with those receiving breast conserving surgery (BCS). An
      additional finding was that as patients' level of involvement in the decision
      process increased, the rate of mastectomy also increased (p<.001). CONCLUSIONS: A
      significant proportion of breast cancer patients experience a decision process
      that matches their preferences for participation, and report satisfaction with
      both the process and the outcome. However, women who report more involvement in
      the decision process are significantly less likely to receive a lumpectomy. Thus,
      increasing patient involvement in the decision process will not necessarily
      increase use of BCS or lead to greater satisfaction. The most salient aspect for
      satisfaction with the decision making process is the match between patients'
      preferences and experiences regarding participation.

PMID- 15960690
TI  - Commentary--surgical decisions after breast cancer: can patients be too involved
      in decision making?

PMID- 15960691
TI  - Health services for women in outpatient substance abuse treatment.
AB  - OBJECTIVE: To evaluate how a sample of outpatient substance abuse treatment units
      respond to organizational and environmental influences by adopting and
      implementing treatment services for women. DATA SOURCES: The National Drug Abuse
      Treatment System Survey from 1995 and 2000, a national survey of outpatient
      substance abuse treatment units. STUDY DESIGN: Health services for women are the
      dependent variables. The predictors include organizational and environmental
      factors that represent resource dependence and institutional pressures for the
      treatment unit. Logistic regression and Heckman selection models were used to
      test hypotheses. DATA COLLECTION: Program directors and clinical supervisors at
      each treatment unit were interviewed by telephone in 1995 and 2000. PRINCIPAL
      FINDINGS: Units that depended on specific funding for women's programs and that
      depended on government funds were more likely to adopt, but not necessarily
      implement, women's services. Methadone units and units that train more staff to
      work with women were more likely to adopt as well as implement women's services.
      Private not-for-profit units were more likely to adopt some services, while for
      profit units were less so. However, in general, neither for-profit nor not-for
      profit units significantly implemented services. There was evidence that the odds
      of adopting services were greater in 2000 than 1995 for two services, but were
      otherwise stable. CONCLUSIONS: There is considerable variation in the adoption
      and implementation of women's services. In addition, not all adopted services
      were significantly implemented, which could reflect limited organizational
      resources and/or conflicting expectations. This also suggests that referral
      mechanisms to these services, and therefore access, may not be adequate.
      Government funds and specific funds for women's programs are important resources
      for the provision of these services. Women's services appear more available in
      methadone units, suggesting that regulation has been influential and that the
      recent methadone accreditation system should be evaluated. Staff training may be
      one strategy to encourage implementation of these services. For the most part,
      the adoption of services for women did not change between 1995 and 2000.

PMID- 15960692
TI  - Do seniors understand their risk of moving to a nursing home?
AB  - OBJECTIVE: To determine whether seniors understand their risk of moving to a
      nursing home. Data Sources. We used longitudinal data from the Asset and Health
      Dynamics Among the Oldest Old (AHEAD) database. AHEAD is a nationally
      representative survey (n=8,203) of community dwellers aged 70+ years and their
      spouses. STUDY DESIGN: We followed respondents for 5 years from the date of the
      first interview fielded in 1993. Our primary dependent variable was whether
      respondents moved to a nursing home within 5 years of baseline; self-assessed
      probability of moving to a nursing home within 5 years, also assessed at
      baseline, was the primary explanatory variable. PRINCIPAL FINDINGS: We found that
      seniors who believed they were more likely to move to a nursing home within 5
      years were indeed more likely to do so, and that most elders overestimated their
      likelihood of moving to a nursing home. CONCLUSIONS: Low rates of private long
      term care insurance are not plausibly a result of seniors underestimating their
      personal risk of moving to a nursing home; such an assumption is inherent in many
      strategies to plan for the future long-term care needs of the baby boom
      generation.

PMID- 15960693
TI  - Not of one mind: mental models of clinical practice guidelines in the Veterans
      Health Administration.
AB  - OBJECTIVE: The purpose of this paper is to present differences in mental models
      of clinical practice guidelines (CPGs) among 15 Veterans Health Administration
      (VHA) facilities throughout the United States. DATA SOURCES: Two hundred and
      forty-four employees from 15 different VHA facilities across four service
      networks around the country were invited to participate. Participants were
      selected from different levels throughout each service setting from primary care
      personnel to facility leadership. STUDY DESIGN: This qualitative study used
      purposive sampling, a semistructured interview process for data collection, and
      grounded theory techniques for analysis. DATA COLLECTION: A semistructured
      interview was used to collect information on participants' mental models of CPGs,
      as well as implementation strategies and barriers in their facility. FINDINGS:
      Analysis of these interviews using grounded theory techniques indicated that
      there was wide variability in employees' mental models of CPGs. Findings also
      indicated that high-performing facilities exhibited both (a) a clear, focused
      shared mental model of guidelines and (b) a tendency to use performance feedback
      as a learning opportunity, thus suggesting that a shared mental model is a
      necessary but not sufficient step toward successful guideline implementation.
      CONCLUSIONS: We conclude that a clear shared mental model of guidelines, in
      combination with a learning orientation toward feedback are important components
      for successful guideline implementation and improved quality of care.

PMID- 15960694
TI  - Just-in-time evidence-based e-mail "reminders" in home health care: impact on
      nurse practices.
AB  - OBJECTIVE: To test the effectiveness of two interventions designed to improve the
      adoption of evidence-based practices by home health nurses caring for heart
      failure (HF) patients. DATA SOURCES/STUDY SETTING: Information on nurse practices
      was abstracted from the clinical records of patients admitted between June 2000
      and November 2001 to the care of 354 study nurses at a large, urban, nonprofit
      home care agency. STUDY DESIGN: The study employed a randomized design with
      nurses assigned to usual care or one of two intervention groups upon
      identification of an eligible patient. The basic intervention was a one-time e
      mail reminder highlighting six HF-specific clinical recommendations. The
      augmented intervention consisted of the initial e-mail reminder supplemented by
      provider prompts, patient education material, and clinical nurse specialist
      outreach. DATA COLLECTION: At each home health visit provided by a study nurse to
      an eligible HF patient during the 45-day follow-up period, a structured chart
      abstraction tool was used to collect information on whether the nurse provided
      the care practices highlighted in the e-mail reminder. PRINCIPAL FINDINGS: Both
      the basic and the augmented interventions greatly increased the practice of
      evidence-based care, according to patient records, in the areas of patient
      assessment and instructions about HF disease management. While not all results
      were statistically significant at conventional levels, intervention effects were
      positive in virtually all cases and effect magnitudes frequently were large.
      CONCLUSIONS: The results of this randomized trial strongly support the efficacy
      of just-in-time evidence-based reminders as a means of changing clinical practice
      among home health nurses who are geographically dispersed and spend much of their
      time in the field.

PMID- 15960695
TI  - Just-in-time evidence-based e-mail "reminders" in home health care: impact on
      patient outcomes.
AB  - OBJECTIVE: To assess the impact and cost-effectiveness of two information-based
      provider reminder interventions designed to improve self-care management and
      outcomes of heart failure (HF) patients. DATA SOURCES/STUDY SETTING: Interview
      and agency administrative data on 628 home care patients with a primary diagnosis
      of HF. STUDY DESIGN: Patients were treated by nurses randomly assigned to usual
      care or one of two intervention groups. The basic intervention was an e-mail to
      the patient's nurse highlighting six HF-specific clinical recommendations. The
      augmented intervention supplemented the initial nurse reminder with additional
      clinician and patient resources. DATA COLLECTION: Patient interviews were
      conducted 45 days post admission to measure self-management behaviors, HF
      specific outcomes (Kansas City Cardiomyopathy Questionnaire-KCCQ), health-related
      quality of life (EuroQoL), and service use. PRINCIPAL FINDINGS: Both
      interventions improved the mean KCCQ summary score (15.3 and 12.9 percent,
      respectively) relative to usual care (p< or =.05). The basic intervention also
      yielded a higher EuroQoL score relative to usual care (p< or =.05). In addition,
      the interventions had a positive impact on medication knowledge, diet, and weight
      monitoring. The basic intervention was more cost-effective than the augmented
      intervention in improving clinical outcomes. CONCLUSIONS: This study demonstrates
      the positive impact of targeting evidence-based computer reminders to home health
      nurses to improve patient self-care behaviors, knowledge, and clinical outcomes.
      It also advances the field's limited understanding of the cost-effectiveness of
      selected strategies for translating research into practice.

PMID- 15960696
TI  - The performance of administrative and self-reported measures for risk adjustment
      of Veterans Affairs expenditures.
AB  - OBJECTIVE: To evaluate the performance of different prospective risk adjustment
      models of outpatient, inpatient, and total expenditures of veterans who regularly
      use Veterans Affairs (VA) primary care. DATA SOURCES: We utilized administrative,
      survey and expenditure data on 14,449 VA patients enrolled in a randomized trial
      that gave providers regular patient health assessments. STUDY DESIGN: This cohort
      study compared five administrative data-based, two self-report risk adjusters,
      and base year expenditures in prospective models. DATA EXTRACTION METHODS: VA
      outpatient care and nonacute inpatient care expenditures were based on unit
      expenditures and utilization, while VA expenditures for acute inpatient care were
      calculated from a Medicare-based inpatient cost function. Risk adjusters for this
      sample were constructed from diagnosis, medication and self-report data collected
      during a clinical trial. Model performance was compared using adjusted R2 and
      predictive ratios. PRINCIPAL FINDINGS: In all expenditure models, administrative
      based measures performed better than self-reported measures, which performed
      better than age and gender. The Diagnosis Cost Groups (DCG) model explained total
      expenditure variation (R2=7.2 percent) better than other models. Prior outpatient
      expenditures predicted outpatient expenditures best by far (R2=42 percent).
      Models with multiple measures improved overall prediction, reduced over
      prediction of low expenditure quintiles, and reduced under-prediction in the
      highest quintile of expenditures. CONCLUSIONS: Prediction of VA total
      expenditures was poor because expenditure variation reflected utilization
      variation, but not patient severity. Base year expenditures were the best
      predictor of outpatient expenditures and nearly the best for total expenditures.
      Models that combined two or more risk adjusters predicted expenditures better
      than single-measure models, but are more difficult and expensive to apply.

PMID- 15960697
TI  - Imputation of SF-12 health scores for respondents with partially missing data.
AB  - OBJECTIVE: To create an efficient imputation algorithm for imputing the SF-12
      physical component summary (PCS) and mental component summary (MCS) scores when
      patients have one to eleven SF-12 items missing. STUDY SETTING: Primary data
      collection was performed between 1996 and 1998. STUDY DESIGN: Multi-pattern
      regression was conducted to impute the scores using only available SF-12 items
      (simple model), and then supplemented by demographics, smoking status and
      comorbidity (enhanced model) to increase the accuracy. A cut point of missing SF
      12 items was determined for using the simple or the enhanced model. The algorithm
      was validated through simulation. DATA COLLECTION: Thirty-thousand-three-hundred
      and eight patients from 63 physician groups were surveyed for a quality of care
      study in 1996, which collected the SF-12 and other information. The patients were
      classified as "chronic" patients if they reported that they had diabetes, heart
      disease, asthma/chronic obstructive pulmonary disease, or low back pain. A follow
      up survey was conducted in 1998. PRINCIPAL FINDINGS: Thirty-one percent of the
      patients missed at least one SF-12 item. Means of variance of prediction and
      standard errors of the mean imputed scores increased with the number of missing
      SF-12 items. Correlations between the observed and the imputed scores derived
      from the enhanced models were consistently higher than those derived from the
      simple model and the increments were significant for patients with > or =6
      missing SF-12 items (p<.03). CONCLUSION: Missing SF-12 items are prevalent and
      lead to reduced analytical power. Regression-based multi-pattern imputation using
      the available SF-12 items is efficient and can produce good estimates of the
      scores. The enhancement from the additional patient information can significantly
      improve the accuracy of the imputed scores for patients with > or =6 items
      missing, leading to estimated scores that are as accurate as that of patients
      with <6 missing items.

PMID- 15960698
TI  - Survival strategies for Michigan's health care safety net providers.
AB  - OBJECTIVE: To understand key adaptive strategies considered by health care safety
      net organizations serving uninsured and underinsured populations in Michigan.
      DATA SOURCES/STUDY SETTING: Primary data collected through interviews at
      community-based free clinics, family planning clinics, local public health
      departments, and Federally Qualified Health Centers from 2002 to 2003. RESEARCH
      DESIGN: In each of six service areas in Michigan, we conducted a multiple-site
      case study of the four organizations noted above. We conducted interviews with
      the administrator, the medical or clinical director, the financial or marketing
      director, and a member of the board of directors. We interviewed 74 respondents
      at 20 organizations. PRINCIPAL FINDINGS: Organizations perceive that unmet need
      is expanding faster than organizational capacity; organizations are unable to
      keep up with demand. Other threats to survival include a sicker patient
      population and difficulty in retaining staff (particularly nurses). Most clinics
      are adopting explicit business strategies to survive. To maintain financial
      viability, clinics are: considering or implementing fees; recruiting insured
      patients; expanding fundraising activities; reducing services; or turning away
      patients. Collaborative strategies, such as partnerships with hospitals, have
      been difficult to implement. Clinics are struggling with how to define their
      mission given the environment and threats to survival. CONCLUSIONS: Adaptive
      strategies remain a work in progress, but will not be sufficient to respond to
      increasing service demands. Increased federal funding, or, ideally, a national
      health insurance program, may be the only viable option for expanding
      organizational capacity.

PMID- 15960699
TI  - Commentary--the history and contradictions of the health care safety net.

PMID- 15960700
TI  - The Global Fund at three years--flying in crowded air space.

PMID- 15960701
TI  - From the Old World to the New World: an ecologic study of population
      susceptibility to HIV infection.
AB  - It remains unclear why the global distribution of human immunodeficiency virus
      (HIV), between and within continents, is so heterogeneous. This ecologic study of
      34 populations of the Americas explored the hypothesis that populations differ in
      their intrinsic, biological susceptibility to HIV which, together with exposure,
      might determine the ultimate 'mature' prevalence. If true, national HIV
      prevalence in populations of the Americas should be predictable from each
      country's ethnic mosaic, inter-racial admixture and HIV prevalence in regions of
      Africa, Europe and Asia from where their ancestors migrated. For each country,
      the adult population (15-49 years) was multiplied by the proportion corresponding
      to each ethnic group by HIV prevalence in the country/region of origin of each
      group, yielding the predicted prevalences, which were then compared with observed
      prevalences documented by UNAIDS for 2001. Predicted and observed HIV prevalences
      were highly correlated (r = 0.70, P < 0.001). In North America, predicted
      prevalences were within 0.5% of the observed values, except for African-Americans
      and African-Canadians. In Central and South America, differences between
      predicted and observed prevalences were <1.0% except in Honduras and Guyana. Some
      Caribbean countries had a predicted prevalence identical to the observed one, but
      there were outliers. Overall, predicted prevalence was 0.93% and observed
      prevalence 0.64%; two-thirds of this difference was attributed to Brazil.
      Although it was not possible to adjust to the confounding effects of sexual
      behaviour and cofactors of transmission (such as sexually transmitted infections)
      because of the lack of nationally representative data for each and every country,
      a number of arguments reviewed in the paper suggest that confounders cannot
      explain all this association and that differential susceptibility might be an
      important determinant of steady-state HIV prevalence.

PMID- 15960702
TI  - Retention and effectiveness of HIV/AIDS training of traditional healers in far
      western Nepal.
AB  - OBJECTIVE: To evaluate HIV/AIDS training for traditional healers (THs) in far
      western Nepal. METHODS: We collected data using a structured questionnaire and
      assessed THs' knowledge of HIV transmission, misconceptions and preventive
      measures immediately prior to the initial training conducted from June to
      December 1999, and then 9-12 months after the training in 2000. We also conducted
      six focus group discussions (FGD) and assessed THs' performances after the
      training. We interviewed 12 key informants about their perceptions towards the
      trained THs. RESULTS: THs significantly improved their knowledge of HIV
      transmission, misconceptions and preventive measures after the training. The FGD
      and key informant interview results showed that the trained THs provided
      culturally acceptable HIV/AIDS education to the local people, distributed condoms
      and played a role in reducing the HIV/AIDS-related stigma. CONCLUSIONS: THs have
      a potential to work as key players in HIV/AIDS programmes in Nepal.

PMID- 15960703
TI  - Rapid assessment of Schistosoma mansoni: the validity, applicability and cost
      effectiveness of the Lot Quality Assurance Sampling method in Uganda.
AB  - Rapid and accurate identification of communities at highest risk of morbidity
      from schistosomiasis is key for sustainable control. Although school
      questionnaires can effectively and inexpensively identify communities with a high
      prevalence of Schistosoma haematobium, parasitological screening remains the
      preferred option for S. mansoni. To help reduce screening costs, we investigated
      the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools
      according to categories of S. mansoni prevalence in Uganda, and explored its
      applicability and cost-effectiveness. First, we evaluated several sampling plans
      using computer simulation and then field tested one sampling plan in 34 schools
      in Uganda. Finally, cost-effectiveness of different screening and control
      strategies (including mass treatment without prior screening) was determined, and
      sensitivity analysis undertaken to assess the effect of infection levels and
      treatment costs. In identifying schools with prevalences > or =50%, computer
      simulations showed that LQAS had high levels of sensitivity and specificity
      (>90%) at sample sizes <20. The method also provides an ability to classify
      communities into three prevalence categories. Field testing showed that LQAS
      where 15 children were sampled had excellent diagnostic performance (sensitivity:
      100%, specificity: 96.4%, positive predictive value: 85.7% and negative
      predictive value: 92.3%). Screening using LQAS was more cost-effective than mass
      treating all schools (US$218 vs. US$482/high prevalence school treated).
      Threshold analysis indicated that parasitological screening and mass treatment
      would become equivalent for settings where prevalence > or =50% in 75% of schools
      and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda,
      LQAS provides a rapid, valid and cost-effective method for guiding decision
      makers in allocating finite resources for the control of schistosomiasis.

PMID- 15960704
TI  - Predictors of compliance with community-directed ivermectin treatment in Uganda:
      quantitative results.
AB  - In order to identify the factors influencing compliance with mass ivermectin
      treatment for onchocerciasis control, a cross-sectional study was carried out in
      Bushenyi District, Uganda. Data were collected by interviewing 839 individuals
      who were randomly selected from 30 clusters where onchocerciasis is endemic.
      Information was collected on compliance with ivermectin treatment, socio
      demographic characteristics, perception of personal susceptibility to
      onchocerciasis, knowledge about cause/transmission of onchocerciasis, knowledge
      of signs and symptoms of onchocerciasis, treatment of onchocerciasis, benefits
      and dangers of taking ivermectin, organization of distribution of ivermectin,
      work and selections of community drug distributors (CDDs), social influence and
      support to take ivermectin and on barriers and supports towards compliance with
      ivermectin treatment. The major factors favouring compliance were: perceiving
      CDDs as doing their work well, believing that measuring height is the best way to
      determine one's dose of ivermectin, having social support from one's family,
      saying that ivermectin treatment costs nothing, perceiving personal risk of
      onchocerciasis, believing that ivermectin prevents onchocerciasis and perceiving
      radios as supporting treatment with ivermectin. The strongest predictor of
      compliance with ivermectin treatment is perceiving CDDs as doing their work well
      with adjusted odds ratios of 5.54 (95% CI: 3.19-9.62). In order to improve
      compliance with ivermectin treatment, CDDs need to be well-facilitated and
      ivermectin distribution should be free. Health education is necessary so that
      people perceive themselves to be at risk of onchocerciasis and to understand the
      rationale of using height for dose determination. The health education should
      target the family and use radios.

PMID- 15960705
TI  - Limited influence of haptoglobin genotypes on severe malaria in Ghanaian
      children.
AB  - Haptoglobin (Hp) polymorphisms in sub-Saharan Africa have been associated with an
      increased risk of severe malaria. However, available data are inconclusive. We
      examined the role of Hp polymorphisms in susceptibility to Plasmodium falciparum
      infection and to severe malaria in northern Ghana. Three groups each of 290 age
      and sex-matched children with severe malaria, children with asymptomatic P.
      falciparum infection and aparasitaemic healthy controls were studied. Hp typing
      was based on PCR. In all children, Hp1-1, Hp2-1, and Hp2-2 occurred in 32.4%,
      54.1%, and 13.5%, respectively. The prevalence of the Hp genotypes did not differ
      significantly between groups. However, Hp2 alleles were least common in healthy
      children (0.379), more frequent in parasitaemic controls (0.402), and most common
      in severe malaria patients (0.434; = 3.7; P = 0.06). In matched pair analysis, no
      Hp genotype increased the risk of severe malaria. However, using Hp1-1 as a
      reference, children with Hp2-2 exhibited a slightly increased risk of severe
      malaria (odds ratio, 1.6; P = 0.04). These results indicate that Hp polymorhisms
      may have a rather limited influence on the development of severe malaria.

PMID- 15960706
TI  - Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian
      children with severe malaria.
AB  - Nitric oxide (NO) has toxic properties against Plasmodium falciparum. While high
      blood levels have been associated with protection against severe malarial
      disease, they may also contribute to the pathophysiology of cerebral malaria and
      severe anaemia. Promoter variants in the inducible nitric oxide synthase (iNOS)
      gene have been shown to influence NO concentrations and disease manifestation.
      However, findings are conflicting. We examined associations of plasma NO
      metabolites (NOx) with symptoms of severe malaria, particularly malarial anaemia
      and cerebral malaria, and with iNOS promoter variants. In 210 Ghanaian children
      with severe malaria, we measured plasma nitrite, nitrate, and S-nitrosothiol, and
      genotyped the iNOS promoter variants -954G-->C, -1173C-->T, and the -2.5 kb
      (CCTTT)(n) microsatellite. NOx levels decreased with age. In young children (<24
      months), high NOx was associated with reduced parasite density. This was not seen
      in patients of 24-48 months of age and reversed in older children. Subgroup
      analysis revealed that in children with severe anaemia but without cerebral
      involvement (prostration, impaired consciousness, convulsions), high NOx levels
      correlated with low parasitaemia (P = 0.02). In these children, elevated NOx
      levels were also associated with the iNOS-954C-->T/(CCTTT)(8) haplotype (P =
      0.03). No association between NOx or iNOS genotypes and cerebral malaria was
      observed. Our findings suggest that in young children with severe malaria NOx
      reduces parasitaemia. This effect wanes at higher ages and may reflect a
      predominance of unspecific immune responses to infection in early childhood. This
      finding may have importance for the understanding of associations between iNOS
      variants and severe malaria in regions of differing disease manifestation.

PMID- 15960707
TI  - Malaria infection among pregnant women attending antenatal clinics in six Rwandan
      districts.
AB  - OBJECTIVES: The aim of the study was to assess the knowledge, attitude and
      practices of pregnant women towards malaria and their association with malaria
      morbidity. METHODS: Cross-sectional malaria survey of 1432 pregnant women
      attending six health centres, each of them situated in a specific health district
      in Rwanda from September to October 2002. RESULTS: The overall prevalence of
      malaria infection was 13.6% and all infections but two were caused by Plasmodium
      falciparum. The six health districts were significantly different in terms of
      malaria prevalence, which varied between 11.5% and 15.4% in four and was <5% in
      the other two districts. The prevalence of anaemia and splenomegaly mirrored that
      of malaria infection. In three districts, the prevalence of infection was
      significantly higher in primigravidae than in secundigravidae and multigravidae
      (P = 0.01), while in two others it did not vary with parity. Bed net use was low 
      only 13.1% of the women had at least one bed net at home and 8.3% of them slept
      under it - and significantly different between districts. Most women knew that
      malaria might have serious consequences for their pregnancy and that insecticide
      treated bed nets are useful for malaria prevention. However, the bed net market
      price [1525 Rwandan Francs (RFr), approximately 1.6] was much higher than that
      considered as affordable and acceptable (389 RFr, approximately 0.3). CONCLUSION:
      Malaria in pregnancy is a major problem in Rwanda, even in the districts of low
      transmission. Bed net use among pregnant women is low. The option of providing
      free insecticide-treated bed nets to pregnant women should be explored and
      possibly implemented; it could rapidly increase bed net use and earlier
      attendance to antenatal clinics with clear benefits for the women's health.

PMID- 15960708
TI  - Community-based surveillance: a pilot study from rural Cambodia.
AB  - OBJECTIVE: This study seeks to assess the performance of a community-based
      surveillance system (CBSS), developed and implemented in seven rural communes in
      Cambodia from 2000 to 2002 to provide timely and representative information on
      major health problems and life events, and so permit rapid and effective control
      of outbreaks and communicable diseases in general. METHODS: Lay people were
      trained as Village Health Volunteers (VHVs) to report suspected outbreaks,
      important infectious diseases, and vital events occurring in their communities to
      local health staff who analysed the data and gave feedback to the volunteers
      during their monthly meetings. RESULTS: Over 2 years of its implementation, the
      system was able to detect outbreaks early, regularly monitor communicable disease
      trends, and to provide continuously updated information on pregnancies, births
      and deaths in the rural areas. In addition, the system triggered effective
      responses from both health staff and VHVs for disease control and prevention and
      in outbreaks. CONCLUSION: A CBSS can successfully fill the gaps of the current
      health facility-based disease surveillance system in the rapid detection of
      outbreaks, in the effective monitoring of communicable diseases, and in the
      notification of vital events in rural Cambodia. Its replication or adaptation for
      use in other rural areas in Cambodia and in other developing countries is likely
      to be beneficial and cost-effective.

PMID- 15960710
TI  - Household pit latrines as a potential source of the fly Musca sorbens--a one year
      longitudinal study from The Gambia.
AB  - OBJECTIVES: To assess whether the trachoma vector Musca sorbens was breeding in
      household latrines in a trachoma-endemic part of The Gambia. METHODS:
      Longitudinal study of flies emerging from 16 sentinel household latrines selected
      at random from a list of all latrines present in four Gambian villages. Latrines
      were surveyed and fly traps were set over the drop hole for 24 h once per month
      for a year. RESULTS: All the sentinel latrines were of the 'Gambian improved
      household latrine' design, which has a cement slab but is not ventilated or fly
      proofed. The latrines were all in regular use by a family, mean number of users
      per latrine 14.8 (SD 8.0, range 2-29). Of 55 351 flies caught in 192 catches 54
      130 (97.8%) were Chrysomya albiceps, 690 (1.2%) Musca domestica, 466 (0.8%)
      Chrysomya regalis and 65 (0.1%) M. sorbens. Of the M. sorbens caught 61 (93.8%)
      were female. CONCLUSIONS: Gambian improved household pit latrines cannot be
      considered a source of the trachoma vector M. sorbens, and the promotion of pit
      latrines as a method to reduce M. sorbens is warranted. A large number of C.
      albiceps were caught emerging from the latrines, but this species is not
      considered to be of medical importance.

PMID- 15960709
TI  - A randomized clinical trial to compare the efficacy of three treatment regimens
      along with footcare in the morbidity management of filarial lymphoedema.
AB  - The progression of lymphoedema to elephantiasis associated with increased
      incidence of episodic adeno-lymphangitis (ADL) is of great concern, as it causes
      physical suffering, permanent disability and economic loss to lymphatic
      filariasis patients. This randomized clinical trial aimed to assess the efficacy
      in terms of reduction of oedema and ADL frequency of three treatment regimens
      among lymphoedema patients from Orissa, India. The regimens were: (I) oral
      penicillin--one tablet of 800 000 U penicillin G potassium twice daily for 12
      days--repeated every 3 months for 1 year; (II) diethylcarbamazine--6 mg/kg
      bodyweight for 12 days-repeated every 3 months for 1 year; and (III) topical
      antiseptic, i.e. betadine ointment. Foot care was part of all regimens. All three
      drug regimens are efficacious in reducing oedema and frequency of ADL episodes.
      Although the efficacy was slightly higher in regimen I, the difference was not
      significant. About half of all patients had reduced oedema after the 90 days of
      treatment, with oedema reduction of 75-100% in 20%. A major proportion of the
      remaining patients had oedema reduced by less than 25%. The proportion of people
      whose oedema reduced was slightly but not significantly lower in regimen II.
      anova revealed that lymphoedema reduction varied according to grade; being
      greatest at grade 1 lymphoedema, followed by grade 2. All three regimens
      significantly reduced ADL frequency after 1 year of treatment. This may be
      because of foot care as well as use of antibiotics. The estimated costs of
      treatment per patient for a period of 3 months are US$2.4, 1.5 and 4.0
      respectively for regimen I, II and III. Thus affordable treatments with simple
      antibiotics and foot care can give substantial relief to the patients and reverse
      early lymphoedema.

PMID- 15960711
TI  - Creutzfeldt-Jakob disease in Kenya.
AB  - OBJECTIVE: To study the pattern of occurrence of Creutzfeldt-Jakob disease (CJD)
      in Kenya. Study design Prospective, cross-sectional, descriptive study of
      clinical, encephalographic and natural history of CJD, backed by histology in as
      many patients as possible. METHODS: Consecutive patients presenting with the
      criteria laid down by WHO expert committee for diagnosis of CJD were recruited
      between January 1990 and May 2004. We analysed the clinical features and
      electroencephalography of all participants and took brain biopsies from four
      patients. RESULTS: There were four definite, seven probable and two possible
      cases. The electroencephalographic and histological features were typical of
      sporadic CJD. CONCLUSION: Sporadic CJD occurs in Kenya and the clinical,
      encephalographic and histological features were no different to those described
      elsewhere. Although we did not see variant, hereditary and iatrogenic forms of
      CJD, neurologists should not exclude these in making diagnoses.

PMID- 15960712
TI  - Spinal anaesthesia for Caesarean section: time for re-appraisal?

PMID- 15960713
TI  - Anaesthesia for Caesarean section and neonatal acid-base status: a meta-analysis.
AB  - Spinal anaesthesia is generally preferred for Caesarean section. Its superiority
      for the baby is often assumed. Umbilical artery acid-base status provides a valid
      index of fetal welfare. Twenty-seven studies reporting neonatal acid-base data
      with different types of anaesthesia were used to compare umbilical artery or vein
      pH and base deficit, using random-effect meta-analysis. Cord pH was significantly
      lower with spinal than with both general (difference: -0.015; 95% CI -0.029 to 
      0.001; 13 studies, 1272 subjects) and epidural anaesthesia (difference -0.013;
      95% CI -0.024 to -0.002; 11 studies, 828 subjects). Larger doses of ephedrine
      contributed to the latter effect (p = 0.023). Sixteen studies reported a base
      deficit, which was significantly higher for spinal than for general (difference
      1.109; 95% CI 0.434-1.784 mEq.l(-1); seven studies, 695 subject) and epidural
      anaesthesia (difference 0.910; 95% CI 0.222-1.598 mEq.l(-1); seven studies, 497
      subjects). Spinal anaesthesia cannot be considered safer than epidural or general
      anaesthesia for the fetus.

PMID- 15960714
TI  - The use of the stroke risk index to predict neurological complications following
      coronary revascularisation on cardiopulmonary bypass.
AB  - The aim of this study was to investigate the validity of the stroke risk index
      (SRI) in identifying patients who develop a stroke following coronary artery
      bypass grafting on cardiopulmonary bypass. Retrospective data were analysed from
      6846 patients who underwent adult coronary artery surgical procedures on
      cardiopulmonary bypass between 1997 and 2003. Patients were risk stratified pre
      operatively using the SRI assessment model into low (Group A < or = 50), medium
      (Group B, 51-100) and high risk (Group C, > 100). A total of 217 patients (3.2%)
      with a mean age 65.9 +/- 11.7 years developed adverse neurological events
      following surgery. The CNS injury risk was 4% in Group A, 23% in Group B, and 8%
      in Group C. Pre-operatively, patients in Group B were older (p < 0.05), had a
      greater proportion of redo operations (OR 3.02; p < 0.001), diabetes mellitus (OR
      2.51; p < 0.05), hypertension (OR 1.64; p < 0.01), myocardial infarction (OR
      3.79; p < 0.05), ejection fraction < 30% (OR 1.46; p < 0.01) and absence of sinus
      rhythm (OR 2.52; p < 0.05) when compared with their counterparts. CNS events
      increased the patients' hospital stay by 40% in Groups A and C (p = 0.04) and 72%
      in Group B (p < 0.001). Only 31% returned home, compared with 85% of patients
      without cerebral complications (p < 0.001). These findings demonstrate that
      factors such as a pre-operative history of redo procedures, myocardial
      infarction, ejection fraction < 30% and absence of sinus rhythm play an important
      role in identifying the at-risk population. We conclude, therefore, that a
      further refinement and validation of the SRI is necessary.

PMID- 15960715
TI  - Effects of short-term propofol administration on pancreatic enzymes and
      triglyceride levels in children.
AB  - This prospective, clinical trial evaluated the effects of short-term propofol
      administration on triglyceride levels and serum pancreatic enzymes in children
      undergoing sedation for magnetic resonance imaging. Laboratory parameters of 40
      children, mean age (SD; range) 67 (66; 4-178) months undergoing short-term
      sedation were assessed before and 4 h after having received propofol. Mean (SD)
      propofol loading dose was 2.2 (1.1) mg.kg(-1) followed by continuous propofol
      infusion of 6.9 (0.9) mg.kg(-1).h(-1). Serum lipase levels (p = 0.035) and serum
      triglyceride levels (p = 0.003) were raised significantly after propofol
      administration but remained within normal limits. No significant changes in serum
      pancreatic-amylase levels were seen (p = 0.127). In two (5%) children, pancreatic
      enzymes and in four (10%) children triglyceride levels were raised above normal
      limits; however, no child showed clinical symptoms of pancreatitis. We conclude
      that even short-term propofol administration with standard doses of propofol may
      have a significant effect on serum triglyceride and pancreatic enzyme levels in
      children.

PMID- 15960716
TI  - Lymphocyte contamination of laryngoscope blades--a possible vector for
      transmission of variant Creutzfeldt-Jakob disease.
AB  - Variant Creutzfeldt-Jakob disease (vCJD) is associated with extensive prion
      infection of lymphoreticular tissues during the prolonged asymptomatic incubation
      period. Instruments exposed to infected tissues of preclinically infected
      individuals during medical or surgical procedures represent a potential risk of
      iatrogenic transmission of vCJD prions. We assessed the frequency of
      contamination with lymphoid tissue of single-use laryngoscope blades used for
      tracheal intubation for general anaesthesia. Using a cyto-centrifugation
      technique, lymphocytes were detected from 30% of laryngoscope blades studied. As
      prions resist routine sterilisation procedures, the use of non-disposable
      laryngoscope blades poses a risk of transmitting vCJD from patient to patient.
      The use of such instruments should be abandoned and disposable alternatives used.

PMID- 15960717
TI  - Movement of the upper cervical spine during laryngoscopy: a comparison of the
      Bonfils intubation fibrescope and the Macintosh laryngoscope.
AB  - The movements of the upper cervical spine were measured by fluoroscopy in 20
      patients during laryngoscopy with the Bonfils intubation fibrescope and the
      Macintosh laryngoscope. Laryngoscopy with both the Bonfils intubation fibrescope
      and the Macintosh laryngoscope resulted in significant extension of the cervical
      spine as compared to the neutral position but this extension was significantly
      less with the Bonfils intubation fibrescope than with the Macintosh (p = 0.001).
      However, the atlanto-occipital distance was significantly greater during
      laryngoscopy with the Bonfils intubation fibrescope (p = 0.002), and the angle
      between the occiput and C1 differed significantly between the two techniques (p =
      0.001). With the Bonfils intubation fibrescope, significantly less extension was
      also found at the C1/C2 and C3/C4 levels (p = 0.001 and p = 0.049, respectively).
      There is therefore significantly less movement of the upper cervical spine during
      laryngoscopy with the Bonfils fibrescope compared with the Macintosh
      laryngoscope.

PMID- 15960718
TI  - The management of accidental dural puncture during labour epidural analgesia: a
      survey of UK practice.
AB  - The management of accidental dural puncture and postdural puncture headache in
      obstetric practice continues to be of great interest. This survey aims to explore
      the current management of this complication in the United Kingdom and compares
      the findings to a similar survey undertaken in 1993. A postal questionnaire was
      sent to all maternity units (n = 248). The return rate was 71%. Of these, 144
      units (85%) now have written guidelines for the management of accidental dural
      puncture compared to 58% in 1993. In 47 units (28%), the epidural catheter is now
      routinely placed intrathecally following accidental dural puncture; in 69 units
      (41%) the catheter is re-sited and in the remaining 53 units (31%) either option
      is allowed. This is in contrast to the previous survey, which found that
      catheters were re-sited in 99% of units. Only 31 units (18%) now limit the second
      stage of labour and 19 (11%) avoid pushing and deliver by ventouse or forceps,
      whilst 116 units (69%) allow labour to take place without any intervention. Only
      44 units (26%) now treat postdural puncture headache with an epidural blood patch
      as soon as it is diagnosed, whereas in 120 units (71%) the blood patch is
      performed only after failure of conservative measures. Due to the large increase
      in the use of the intrathecal catheter following this complication, a follow-up
      questionnaire was posted 5 months later to those units (n = 99) that reported
      this practice in the initial survey, with a 94% response rate. The two most
      commonly cited reasons for intrathecal catheterisation were to avoid further
      dural puncture (76%) and to allow immediate analgesia for labour (75%).

PMID- 15960719
TI  - Distance between the skin and the thoracic paravertebral space.
AB  - A fundamental requirement for the safe and effective performance of paravertebral
      blockade is reliable estimates of the depth from skin to paravertebral space at
      different thoracic levels. This distance was assessed using a nerve stimulator
      guided paravertebral blockade technique in 527 separate blocks in 186 patients
      scheduled for various surgical procedures on the trunk. The median skin
      paravertebral depth was 55.0 mm. The skin-paravertebral distance at upper (T1-3)
      and lower (T9-12) thoracic levels were significantly greater than mid-thoracic
      levels (T4-8) (p < 0.05). Body mass index significantly influences this depth at
      upper and lower thoracic levels (p < 0.001) but not in the mid-thoracic region.

PMID- 15960720
TI  - Anabolic steroid abuse: physiological and anaesthetic considerations.
AB  - This review summarises the physiological and pharmacological effects of the
      anabolic steroids used to enhance performance in sports. The anabolic steroids
      promote muscle growth and protein synthesis. Side-effects of anabolic steroids
      include cardiomyopathy, atherosclerosis, hypercoagulopathy, hepatic dysfunction,
      and psychiatric and behavioural disturbances. It is therefore appropriate that
      the anaesthetist be familiar with the abuse of anabolic steroids, their potential
      adverse effects, and the peri-operative risk associated with the use of these
      drugs.

PMID- 15960721
TI  - Acute and chronic pain following craniotomy: a review.
AB  - Postoperative pain is an important clinical problem that has received increasing
      attention in recent years. However, pain following craniotomy has been a
      comparatively neglected topic; this review seeks to redress this imbalance. A
      brief overview of the anatomy of the skull and its linings is given, with
      particular reference to innervation. The various approaches for craniotomies are
      classified, with their association with acute and long-term effects on analgesic
      requirements. A comprehensive search of the literature was undertaken to
      ascertain the incidence of acute pain post craniotomy and current thoughts on
      pharmacological management, touching briefly on pre-emptive treatment. Also
      discussed is the much neglected but nevertheless real incidence of chronic pain
      following craniotomy and its underlying pathogenesis, prevention and treatment.

PMID- 15960722
TI  - Performance of automated air tonometry under hypothermia.
AB  - Intestinal tonometry is used during hypothermic cardio-pulmonary bypass surgery
      to assess splanchnic perfusion. In an in vitro set-up the performance of
      automated air tonometry (TONOCAP) was tested for normo- and hypothermia. A 14-FG
      tonometry catheter was built into a testing chamber (100 cm(3)) perfused with
      blood from a cardio-pulmonary bypass circuit with P(a)co(2) held at 5.6-5.8 kPa
      (alpha-stat). P(r)co(2) from the balloon of the tonometry catheter was measured
      at intervals of 10 min at 37 degrees C and at 25 degrees C by the TONOCAP. Bias
      (precision) of P(r)co(2) - P(a)co(2 alpha-stat) and P(r)co(2) -P(a)co(2 pH-stat)
      at 37 degrees C blood temperature were low at 0.23 kPa (0.21) each.
      Tonometrically measured P(r)co(2) at 25 degrees C significantly differed from
      P(a)co(2 alpha-stat) bias (precision) of 2.00 kPa (0.11) but was similar to
      P(a)co(2 pH-stat) (0.30 kPa (0.11)). P(r)co(2) values as measured by the TONOCAP
      represent pH-stat approach. Identical blood gas management (pH- or alpha-stat)
      should be used for calculation of mucosal-arterial CO(2) difference (P(r-a)co(2)
      gap) or calculation of intramucosal pH.

PMID- 15960723
TI  - Clinical evaluation of the "T-Dagger": a new bedside percutaneous dilational
      tracheostomy device.
AB  - A number of percutaneous dilational tracheostomy devices are now available for
      clinical use. Recently, a new percutaneous dilational tracheostomy device, the "T
      Dagger" (Criticure Invasives, India), has been introduced for rapid bedside
      percutaneous tracheostomy. In a prospective preliminary study, we have performed
      percutaneous dilational tracheostomy (PDT) using the T-Dagger in 20 adult
      ventilated patients in order to evaluate the safety and efficacy of the new
      device. The T-Dagger facilitated bedside PDT in about 3 min with no untoward
      incidents. There was no significant bleeding, pneumothorax, pneumomediastinum,
      tracheal wall injuries or difficulty in ventilation in any of the patients. We
      conclude that the T-Dagger shows early promise in bedside percutaneous dilational
      tracheostomy. However, controlled studies are required in a larger patient
      population before it can be recommended for routine use.

PMID- 15960724
TI  - Transient fixation on a non-native language associated with anaesthesia.

PMID- 15960725
TI  - Peri-operative myocardial ischaemia.

PMID- 15960726
TI  - Prescription errors in Intensive Care.

PMID- 15960727
TI  - Hand positions and the "son-of-Doughty" technique.

PMID- 15960728
TI  - "Doughty" technique.

PMID- 15960729
TI  - Complications of percutaneous tracheostomy in obese patients.

PMID- 15960730
TI  - Routine pre-oxygenation.

PMID- 15960731
TI  - Evaluation of a trans-oesophageal Doppler probe in awake subjects.

PMID- 15960732
TI  - Evaluation of a needle-free system for delivery of skin anaesthesia.

PMID- 15960733
TI  - The Cardiff paediatric laryngoscope and its "non-conforming" siblings.

PMID- 15960734
TI  - Two late-onset postdural puncture headaches.

PMID- 15960735
TI  - Unusually shaped Guedel airways.

PMID- 15960736
TI  - Labelling of prefilled syringes of emergency drugs.

PMID- 15960737
TI  - Ventricular fibrillation following atropine-neostigmine mixture in a patient with
      undiagnosed mitral valve prolapse.

PMID- 15960738
TI  - Herbal medicines and postoperative haemorrhage.

PMID- 15960739
TI  - Fixation of the ProSeal Laryngeal Mask Airway with a gauze bandage.

PMID- 15960745
TI  - Biotechnological potential within the genus Burkholderia.
AB  - Many species within the genus Burkholderia possess significant biotechnological
      potential in bioremediation and biological control. Here we provide a description
      of the Burkholderia strains being investigated for their ability to degrade major
      xenobiotic pollutants and update information on their taxonomy, metabolic
      capacity and genomes.

PMID- 15960746
TI  - Species-directed 16S rRNA gene nested PCR detection of Olsenella species in
      association with endodontic diseases.
AB  - AIMS: To investigate the occurrence of Olsenella uli and Olsenella profusa in
      samples taken from infections of endodontic origin using a devised 16S RNA gene
      based nested PCR protocol. METHODS AND RESULTS: DNA extracted from clinical
      samples was initially amplified using universal 16S rRNA gene primers followed by
      a second round of amplification using the first PCR products to detect a specific
      fragment of either O. uli or O. profusa 16S rRNA gene. Olsenella uli was detected
      in 27% of samples from teeth with asymptomatic periradicular lesions and in 20%
      of pus samples taken from symptomatic (abscess) lesions. Olsenella profusa was
      detected in 7% of asymptomatic teeth and in 13% of symptomatic teeth. A new
      Olsenella phylotype was also detected. CONCLUSIONS: Olsenella species can take
      part in the microbiota associated with infections of the root canal of human
      teeth and a role in the pathogenesis of periradicular diseases is suspected.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present study demonstrates that
      molecular genetic methods keep expanding the list of candidate endodontic
      pathogens to include Olsenella species.

PMID- 15960747
TI  - Genetic characterization of Chromobacterium isolates from black water
      environments in the Brazilian Amazon.
AB  - AIMS: To isolate and to characterize the diversity of Chromobacterium violaceum
      from the Brazilian Amazon region. METHODS AND RESULTS: Twenty-two isolates were
      obtained from the waters and banks of the river Negro, in the Brazilian Amazon.
      All isolates were able to grow in vitro at 44 degrees C and pH 4.0, but were
      adversely affected by temperatures below 15 degrees C, and unable to survive at 4
      degrees C, properties that may be related to the adaptation to the ecosystem. The
      isolates were joined at a final level of similarity of only 13% in the rep-PCR
      analysis. The analysis of 16S rRNA genes resulted in three main groups clustered
      at a final level of similarity of 97% and only three isolates were clustered with
      the type strain. Similar data were obtained for the 23S rRNA gene. CONCLUSIONS: A
      high level of genetic diversity was verified with indications that the Brazilian
      isolates would fit into at least two new clusters besides C. violaceum species.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The results show remarkable bacterial
      adaptability and genetic diversity of C. violaceum in the Amazon region.

PMID- 15960748
TI  - In vivo enzymatic digestion, in vitro xylanase digestion, metabolic analogues,
      surfactants and polyethylene glycol ameliorate laccase production from Ganoderma
      sp. kk-02.
AB  - AIMS: The effect of in vivo enzymatic digestion (IVED), in vitro xylanase
      digestion (IVXD), metabolic analogues, surfactants and polyethylene glycol (PEG)
      on laccase production from Ganoderma sp. kk-02 was studied. METHODS AND RESULTS:
      An acidic laccase producing Ganoderma sp. kk-02 produced 16.0 U ml(-1) and 365.0
      U g(-1) of laccase, when grown under submerged (SmF) and solid state (SSF)
      fermentation conditions, respectively. Modification of the substrate (wheat bran)
      molecular architecture by IVED and IVXD increased subsequent laccase production
      from Ganoderma sp. kk-02 by 1.31-fold (21.0 U ml(-1)) (SmF); 2.21-fold (810.0 U
      g(-1)) (SSF) and 1.10-fold (18.0 U ml(-1)) (SmF); 1.78-fold (650.0 U g(-1)) (SSF)
      when compared with untreated wheat bran. Further enhancement in laccase yield
      under SmF and SSF was obtained when IVED treated wheat bran was used in
      conjunction with amino acids [DL-tryptophan, 2.66-fold (56.0 U ml(-1)) SmF; 2.86
      fold (2324.0 U g(-1)) SSF], vitamins [biotin, 1.71-fold (36.0 U ml(-1)) SmF; 3.06
      fold (2483.0 U g(-1)) SSF], surfactants [Tween-40, 1.85-fold (39.0 U ml(-1)) SmF;
      2.25-fold (1828.0 U g(-1)) SSF], and PEG [PEG 6000, 1.93-fold (40.0 U ml(-1))
      SmF; 1.58-fold (1284.0 U g(-1)) SSF]. CONCLUSIONS: The IVED of substrate (wheat
      bran) facilitated hyper laccase production in presence of additives from
      Ganoderma sp. kk-02. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights a
      new methodology viz. IVED for concomitant and economic production of diverse
      enzymes using the same substrate. The hyper laccase levels obtained could improve
      the economic competitiveness of environmentally benign processes applied in
      varied industries. The work also provides an insight into the regulation of
      complex metabolic pathways governing the expression of extra cellular proteins
      from white-rot fungi.

PMID- 15960749
TI  - pH effects on 10 Streptomyces spp. growth and sporulation depend on nutrients.
AB  - AIMS: Streptomycetes are regarded to prefer neutral to alkaline environmental pH,
      although they commonly occur at remarkably variable pH and nutritional
      conditions. Therefore, the dependence of 10 Streptomyces spp. pH tolerance on
      nutrients was determined. METHODS AND RESULTS: Ten environmental Streptomyces
      spp. were grown and sporulated between pH 4.0 and 11.5, at the interval of 1.5,
      on starch-casein-KNO(3), tryptone-yeast extract-glucose, glycerol-arginine and
      tryptone-soy agars, and three their modifications. On media with starch and
      casein; glucose, tryptone and yeast extract; tryptone and soy peptone; and
      glycerol-arginine and yeast extract strains grew over a broad pH range between
      4.0-5.5 and 10.0-11.5. On glycerol-arginine and on medium with Na-propionate,
      NH(4)NO(3) and yeast extract, streptomycetes grew optimally at pH 7.0 and above.
      The high organic load enabled the growth over a wide pH range. The sporulation pH
      ranges followed those for growth. CONCLUSIONS: The high organic load enabled the
      growth over a wide pH range. The strain-specific differences in sporulation were
      greater than those caused by pH. The best medium for sporulation contained
      glucose and tryptone with minerals of glycerol-arginine agar at pH 5.5.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The growth pH ranges, pH ranges for the
      optimal growth, and sporulation were strongly dependent on nutrients.

PMID- 15960750
TI  - Antimicrobial resistance of Salmonella spp. from pigs at slaughter in Spain in
      1993 and 2001.
AB  - AIM: To compare the incidence of antimicrobial resistance among Salmonella
      serotypes isolated in a pig slaughterhouse in Zaragoza (Spain) during 1993 and
      2001. METHODS AND RESULTS: A total of 168 isolates representing 10 serotypes were
      examined by disc diffusion method using 17 antibiotics. Data showed that the
      majority of the strains were resistant to streptomycin (97%), sulfadiazine
      (93.4%) and tetracycline (83.3%). A large proportion of the collection was
      multidrug resistant (MDR, resistance to four or more antibiotics) with a greater
      incidence in 2001. The findings imply an increasing incidence of MDR amongst S.
      Typhimurium, and all S. Typhimurium-definitive phage type (DT) 104 isolates were
      resistant to ampicillin, chloramphenicol, streptomycin, sulphonamide and
      tetracycline (R-ACSSuT). This resistance phenotype had spread among other phage
      and serotypes. Salmonella Ohio was also a MDR serotype and this is not a serotype
      normally associated with drug resistance. CONCLUSIONS: A large proportion of the
      strains were MDR and this showed that pork products could be a potential vehicle
      of MDR Salmonella food-borne infections. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The findings may have significant public health consequences and could contribute
      to the development of useful practices aimed at limiting the transmission of MDR
      Salmonella serotypes through the food chain.

PMID- 15960752
TI  - Effects of a topical essential oil-containing formulation on biofilm-forming
      coagulase-negative staphylococci.
AB  - AIMS: To evaluate the antimicrobial effects of Polytoxinol (PT), a topical
      essential oil-based formulation, against biofilm positive strains of coagulase
      negative staphylococci. METHODS AND RESULTS: Using a microtitre plate assay we
      measured inhibitory effects for PT against a selection of biofilm-forming
      clinical isolates of coagulase-negative staphylococci. Susceptibility varied
      considerably (MIC = 0.6-20 000 ppm). For the most tolerant clinical isolate
      (Staphylococcus warneri) biofilm growth was inhibited by a 32-fold lower PT
      concentration than planktonic growth. This inhibition of biofilm development,
      which was not observed with the other test isolates, was related to an inhibition
      of the initial phase of S. warneri cell adherence to the polystyrene surface.
      CONCLUSION: The antimicrobial efficacy of PT was verified against clinical
      isolates of coagulase-negative staphylococci in vitro. PT was able to inhibit
      biofilm formation in the most tolerant isolate at sub-inhibitory concentrations.
      SIGNIFICANCE AND IMPACT OF THE STUDY: These observations indicate that an ability
      to prevent biofilm formation, independently of effects on cell viability may
      contribute to the in vivo topical efficacy of essential oils.

PMID- 15960751
TI  - Analysis of the large bowel microbiota of colitic mice using PCR/DGGE.
AB  - AIM: To test combined polymerase chain reaction amplification of 16S rRNA gene
      sequences and denaturing gradient gel electrophoresis (PCR/DGGE) as an analytical
      method to investigate the composition of the large bowel microbiota of mice
      during the development of colitis. METHODS AND RESULTS: The colonic microbiota of
      formerly germfree interleukin 10 (IL-10)-deficient mice that had been exposed to
      the faecal microbiota of specific pathogen-free animals was screened using
      PCR/DGGE. The composition of the large bowel microbiota of IL-10-deficient mice
      changed as colitis progressed. DNA fragments originating from four bacterial
      populations ('Bacteroides sp.', Bifidobacterium animalis, Clostridium cocleatum,
      enterococci) were more apparent in PCR/DGGE profiles of colitic mice relative to
      non-colitic animals, whereas two populations were less apparent (Eubacterium
      ventriosum, Acidophilus group lactobacilli). Specific DNA:RNA dot blot analysis
      showed that bifidobacterial ribosomal RNA (rRNA) abundance increased as colitis
      developed. CONCLUSIONS: PCR/DGGE was shown to be an effective method to
      demonstrate changes in the composition of the large bowel microbiota of mice in
      relation to progression of inflammatory disease. The intensity of staining of DNA
      fragments in DGGE profiles reflected increased abundance of bifidobacterial rRNA
      in the microbiota of colitic animals. As bifidobacterial fragments in PCR/DGGE
      profiles generated from microbiota DNA showed increased intensity of fragment
      staining, an increase in bifidobacterial numbers in colitic mice was indicated.
      SIGNIFICANCE AND IMPACT OF THE STUDY: PCR/DGGE analysis demonstrated an altered
      composition of the large bowel microbiota of colitic mice. This work will allow
      specific groups of bacteria to be targeted in future research concerning the
      pathogenesis of colitis.

PMID- 15960753
TI  - Aerosolization as novel sanitizer delivery system to reduce food-borne pathogens.
AB  - AIMS: As a preliminary experiment on new sanitizer delivery tools, the efficacy
      of aerosolized sanitizer on food-borne pathogens was investigated in larger model
      chamber system. METHODS: Peroxyacetic acid and hydrogen peroxide were aerosolized
      in a model system against artificially inoculated target micro-organisms on
      laboratory media. Cultures of four different food-borne pathogens were inoculated
      and affixed onto three different heights (bottom, wall and ceiling), and three
      different orientations (face-down, vertical and face-down) inside a commercial
      semi-trailer cabinet (14.6 x 2.6 x 2.8 m). Sanitizer was aerosolized into 2
      microm droplet size fog and treated for 1 h at ambient temperature. RESULTS:
      Populations of Bacillus cereus, Listeria innocua, Staphylococcus aureus, and
      Salmonella typhimurium were reduced by an average of 3.09, 7.69, 6.93 and 8.18
      log units per plate respectively. Interestingly, L. innocua, Staph. aureus, and
      Salm. typhimurium showed statistically not different (P >/= 0.05) reduction
      patterns relative to height and orientation that were never expected in a
      spraying system. CONCLUSIONS: Aerosolized sanitizers diffuse like gaseous
      sanitizers. SIGNIFICANCE AND IMPACT OF THE STUDY: Aerosolization has great
      potential for use in commercial applications.

PMID- 15960754
TI  - Real-time PCR detection of Biscogniauxia mediterranea in symptomless oak tissue.
AB  - AIMS: Real-time PCR, based on TaqMan chemistry, was used to detect Biscogniauxia
      mediterranea, a fungal pathogen that after a long endophytic phase may cause
      charcoal disease in oak trees. METHODS AND RESULTS: Specific primers and probe
      were designed and tested on axenic cultures of B. mediterranea and other fungi
      commonly colonizing oaks. Twig samples were collected in Tuscany from apparently
      healthy oaks (Quercus cerris, Quercus ilex and Quercus pubescens) growing near
      trees infected with the fungus. Twigs were divided into two groups: one for
      isolation in agar plates, and one for real-time PCR after DNA extraction. The
      detection limit of the assay was 0.01 pg/DNA, whereas the amounts of fungal DNA
      detected in asymptomatic tissue were >0.5 pg microg(-1) total DNA extracted. In
      the apparently healthy twigs the frequency of isolation found on agar was 25.0%,
      much lower than that with real-time PCR (96.4%). CONCLUSIONS: Real-time PCR is a
      sensitive and fast technique able to specifically detect and quantify the DNA of
      B. mediterranea in oak tissue. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      diagnostic method is a precise tool to localize fungi in symptomless plant
      tissues and promises to advance our understanding of fungal infection during
      their latent phase.

PMID- 15960755
TI  - Characterization of a xylanase from the newly isolated thermophilic Thermomyces
      lanuginosus CAU44 and its application in bread making.
AB  - AIMS: A xylanase from the newly isolated thermophilic fungus, Thermomyces
      lanuginosus CAU44, was characterized and evaluated for its suitability in bread
      making. METHODS AND RESULTS: Xylanase was purified 3.5-fold to homogeneity with a
      recovery yield of 32.8%. It appeared as a single protein band on SDS-PAGE gel
      with a molecular mass of c. 25.6 kDa. The purified xylanase had an optimum pH of
      6.2, and it was stable over pH 5.6-10.3. The optimal temperature of xylanase was
      75 degrees C and it was stable up to 65 degrees C at pH 6.2. Study was further
      carried out to investigate the effect of the purified xylanase on the properties
      of wheat bread and its staling during storage. CONCLUSIONS: The purified xylanase
      from T. lanuginosus CAU44 was stable up to 65 degrees C and had a broad pH range.
      The presence of thermostable xylanase during bread making led to an improvement
      of the specific bread volume and better crumb texture. Besides, addition of
      xylanase provided an anti-staling effect. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The xylanase from the newly isolated Thermomyces lanuginosus CAU44 shows great
      promise as a processing aid in the bread-making industry.

PMID- 15960756
TI  - Susceptibility of Clostridium perfringens to C-C fatty acids.
AB  - AIMS: To determine susceptibility of Clostridium perfringens strains CCM 4435(T)
      and CNCTC 5459 to C(2)-C(18) fatty acids, and evaluate influence of pH in
      cultures grown on glucose. Straw particles were added to cultures to simulate the
      presence of solid phase of the digestive tract milieu. METHODS AND RESULTS:
      Antimicrobial activity of fatty acids was expressed as a concentration at which
      only 50% of the initial glucose was utilized. Lauric acid showed the highest
      antimicrobial activity, followed by myristic, capric, oleic and caprylic acid.
      Only strain CNCTC 5459 was susceptible to linoleic acid. Neither caproic acid and
      acids with a shorter carbon chain nor palmitic and stearic acid influenced
      substrate utilization. The antimicrobial activity of myristic, oleic and linoleic
      acid decreased when clostridia were grown in the presence of straw particles. In
      cultures of both strains treated with capric and lauric acid at pH 5.0-5.3, the
      number of viable cells was <10(2) ml(-1). Only lauric acid reduced number of
      viable cells of both strains below 10(2) ml(-1) at pH > 6. Transmission electron
      microscopy revealed separation of inner and outer membranes and cytoplasma
      disorganization in cells treated with lauric acid. CONCLUSIONS: Lauric acid had
      the highest activity towards C. perfringens among fatty acid tested. Its activity
      was not influenced by the presence of solid particles and did not cease at pH >
      6. SIGNIFICANCE AND IMPACT OF THE STUDY: Lauric acid might be a means for control
      of clostridial infections in farm animals.

PMID- 15960757
TI  - Ecology of Arcobacter species in chicken rearing and processing.
AB  - AIMS: To investigate whether Arcobacter spp. colonize the poultry-rearing
      environment or whether they are contaminants acquired during transportation
      and/or from the processing plant. METHODS AND RESULTS: Samples were collected on
      poultry farms and in the processing plant during slaughter and dressing. Two
      cultural methods of detection were used. Isolates were identified to species
      level using a multiplex-polymerase chain reaction (m-PCR) method, either on the
      initial suspensions, or after enrichment, or on pure cultures of isolates. Of the
      62 samples examined from poultry farms, arcobacters were found only outside the
      rearing sheds (in effluent sludge and stagnant water). Thirty-four samples were
      examined from the processing plant and 26 were positive for arcobacters. All the
      isolates were Arcobacter butzleri. Arcobacters were not found in any sample by
      direct plating nor by m-PCR on the initial suspensions, thus it was concluded
      that numbers were very low. CONCLUSIONS: Arcobacter spp. were not found in
      samples from the live birds and their immediate environment, but A. butzleri was
      found in effluent sludge and stagnant water outside the rearing sheds. However,
      A. butzleri is common in poultry abattoirs, and it appears that poultry carcasses
      are contaminated during processing. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Arcobacters are not found inside poultry-rearing sheds, but are contaminants in
      the processing environment.

PMID- 15960758
TI  - Detection and recovery rates achieved using direct plate and
      enrichment/immunomagnetic separation methods for Escherichia coli O157:H7 in
      minced beef and on bovine hide.
AB  - AIMS: To assess the detection and recovery rates achieved with commonly used
      cultural methods for the enumeration and recovery of Escherichia coli O157:H7
      from minced beef and bovine hide. METHODS AND RESULTS: Minced beef and bovine
      hide were inoculated with varying concentrations (log(10) 1.58-2.58 CFU g(-1) and
      log(10) 2.42-4.49 CFU 100 cm(2) respectively) of E. coli O157:H7 and recovered
      using a direct plate method or an enrichment/immunomagnetic separation (IMS)
      method and then plated onto SMAC or SMAC-CT in both cases. The direct plate
      method detected the pathogen consistently from minced beef samples with an
      average recovery of 69.2-91.2%. From faecal material on the bovine hide the
      recovery of the pathogen ranged from 1.80 to 64.5% with fresh faeces depending on
      the inocula while from dried faeces on hide the results ranged from no recovery
      at all to 25.1%. Enrichment/IMS recovered E. coli O157:H7 at all inocula levels
      tested in minced beef while the pathogen was only detected consistently at an
      average inocula level of log(10) 2.73 CFU 100 cm(2) from fresh faeces and log(10)
      4.49 CFU 100 cm(2) from dried faeces on bovine hide. CONCLUSIONS: The direct
      count enumeration method for E. coli O157:H7 underestimated the numbers of
      pathogens present. The enrichment/IMS procedure consistently detected the
      pathogen from minced beef but did not always detect E. coli O157:H7 from faeces
      on bovine hide. SIGNIFICANCE AND IMPACT OF THE STUDY: Overall this study
      highlights that any microbial data, used in either predictive microbiology or
      risk assessment, must take account of the sensitivity and associated performance
      of the methods employed, in order to make an accurate reflection of the true
      microbiology of the examined sample.

PMID- 15960759
TI  - An extract from teak (Tectona grandis) bark inhibited Listeria monocytogenes and
      methicillin resistant Staphylococcus aureus.
AB  - AIMS: The aim of this study was to characterize the inhibitory mechanism in teak
      (Tectona grandis) bark and to determine its effectiveness against Listeria
      monocytogenes and methicillin resistant Staphylococcus aureus (MRSA). METHODS AND
      RESULTS: Methanol extracts of teak bark were inhibitory to L. monocytogenes and
      MRSA by means of disc diffusion. Gas chromatography-mass spectrometry, and (1)H
      and (13)C nuclear mass resonance analyses revealed that the inhibitory compound
      had a molecular weight of 174, and a structure of 5-hydroxy-1,4-naphthalenedione
      (Juglone). CONCLUSIONS: 5-hydroxy-1,4-naphthalenedione (Juglone) inhibited L.
      monocytogenes and MRSA. SIGNIFICANCE AND IMPACT OF THE STUDY: A compound in an
      extract of teak bark was inhibitory to L. monocytogenes and MRSA.

PMID- 15960760
TI  - Rumen microbial population dynamics in response to photoperiod.
AB  - AIMS: This work was carried out to determine if there was a difference in the
      microbial population of the rumen associated with daylength at which sheep are
      housed. METHODS AND RESULTS: Denaturing gradient gel electrophoresis (DGGE) was
      used to study the ciliate and bacterial diversity in the rumen of Soay rams kept
      in long day (16 h light) or short day (8 h light) photoperiods. Bacterial
      diversity varied according to the daylength conditions where the host animal was
      housed, as did total volatile fatty acids (VFA) concentrations. No differences
      associated with daylength were detected in ciliate diversity, branched VFA
      concentrations or the ruminal ammonia concentrations. CONCLUSIONS: As diets had
      identical composition, yet voluntary intakes levels were higher during long days,
      it is proposed that the differences in bacterial populations arise because of the
      differences in amount of food consumed. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      outcome of this study demonstrated that factors beyond dietary composition must
      be taken into account when trying to study microbial populations, even in what
      can be considered a fairly constant environment.

PMID- 15960761
TI  - 2005 Meeting of the Peripheral Nerve Society, July 9-13, 2005, Tuscany, Italy.
      Abstracts.

PMID- 15960762
TI  - Testosterone-immunopositive primordial germ cells in the testis of the bullfrog,
      Rana catesbeiana.
AB  - In amphibia, steroidogenesis remains quiescent in distinct seasonal periods, but
      the mechanism by which spermatogenesis is maintained under low steroidogenic
      conditions is not clear. In the present study, testosterone location in the
      testes of Rana catesbeiana was investigated immunohistochemically during breeding
      (summer) and nonbreeding (winter) periods. In winter, the scarce interstitial
      tissue exhibited occasional testosterone immunopositivity in the interstitial
      cells but the cytoplasm of primordial germ cells (PG cells) was clearly
      immunopositive. By contrast, in summer, PG cells contained little or no
      immunoreactivity whereas strong immunolabelling was present in the well-developed
      interstitial tissue. These results suggest that PG cells could retain
      testosterone during winter. This androgen reservoir could be involved in the
      control of early spermatogenesis in winter and/or to guarantee spermiogenesis and
      spermiation in the next spring/summer. The weak or negative immunoreaction in the
      summer PG cells might reflect consumption of androgen reservoir by the intense
      spermatogenic activity from spring to summer. Thus, besides acting as stem cells,
      PG cells of R. catesbeiana could exert an androgen regulatory role during
      seasonal spermatogenesis.

PMID- 15960763
TI  - Anatomy of the lactating human breast redefined with ultrasound imaging.
AB  - The aim of this study was to use ultrasound imaging to re-investigate the anatomy
      of the lactating breast. The breasts of 21 fully lactating women (1-6 months post
      partum) were scanned using an ACUSON XP10 (5-10 MHz linear array probe). The
      number of main ducts was measured, ductal morphology was determined, and the
      distribution of glandular and adipose tissue was recorded. Milk ducts appeared as
      hypoechoic tubular structures with echogenic walls that often contained echoes.
      Ducts were easily compressed and did not display typical sinuses. All ducts
      branched within the areolar radius, the first branch occurring 8.0 +/- 5.5 mm
      from the nipple. Duct diameter was 1.9 +/- 0.6 mm, 2.0 +/- 90.7 mm and the number
      of main ducts was 9.6 +/- 2.9, 9.2 +/- 2.9, for left and right breast,
      respectively. Milk ducts are superficial, easily compressible and echoes within
      the duct represent fat globules in breastmilk. The low number and size of the
      ducts, the rapid branching under the areola and the absence of sinuses suggest
      that ducts transport breastmilk, rather than store it. The distribution of
      adipose and glandular tissue showed wide variation between women but not between
      breasts within women. The proportion of glandular and fat tissue and the number
      and size of ducts were not related to milk production. This study highlights
      inconsistencies in anatomical literature that impact on breast physiology,
      breastfeeding management and ultrasound assessment.

PMID- 15960764
TI  - Beyond the initial axon segment of the spinal motor axon: fasciculated
      microtubules and polyribosomal clusters.
AB  - Dense undercoating, microtubular fascicles and scattered polyribosomal clusters
      have until now been considered to be the three structural features of the initial
      segment, and were thought not to extend beyond the initial segment into the
      myelinated parts of the axon. The aim of the present study was to make clear
      whether there is a sudden change in morphology between the unmyelinated and
      myelinated part. We followed spinal motor axons from the initial segment to the
      first internode by conventional electron microscopy and serial sectioning, and
      found that the microtubular fascicles and polyribosomal clusters do exist in the
      internodal axoplasm. The fasciculated microtubules were observed mainly in the
      first paranode. The polyribosomal clusters were found along the course of the
      first internode at a random distance, however, they occurred mainly in the
      proximal part of the first internode. The proportion of sections in which
      ribosomes were found, i.e. the incidence of ribosomes, in the first 30-microm
      long portion was 71 +/- 24% (mean +/- SD, n = 4), and significantly different
      from that in the second 30-microm-long portion (3.2 +/- 1.3%) (mean +/- SD, n =
      4) (P < 0.005). The more distal part of the first internode was not investigated.

PMID- 15960765
TI  - Morphometric and immunohistochemical study of the omasum of red deer during
      prenatal development.
AB  - The red deer is an important study species because of its value in the national
      economy and because it provides a wealth of genetic material. To date, there has
      been little research into the prenatal development of the stomach of ruminants,
      and none of the red deer. We therefore performed a histological evaluation of the
      ontogenesis of the omasum in the red deer. Histomorphometric and
      immunohistochemical analyses were carried out on 50 embryos and fetuses of deer
      from the initial stages of prenatal life until birth. For test purposes, the
      animals were divided into five experimental groups: Group I (1.4-3.6 cm crown
      rump length, CRL; 30-60 days, 1-25% of gestation); Group II (4.5-7.2 cm CRL; 67
      90 days, 25-35% of gestation); Group III (8-19 cm CRL; 97-135 days, 35-50% of
      gestation); Group IV (21-33 cm CRL; 142-191 days, 50-70% of gestation); and Group
      V (36-40 cm CRL; 205-235 days, 75-100% of gestation). At 67 embryonic days, the
      omasum wall was differentiated, and comprised three layers: the epithelial layer,
      pluripotential blastemic tissue and serosa. The stratification of the epithelial
      layer was accompanied by changes in its structure, with the appearance of four
      laminae of different sizes; in order of appearance these were: primary at 67
      days, secondary at 90 days, tertiary at 97 days and quaternary at 135 days. At
      around mid-gestation, lateral evaginations were formed from the stratum basale of
      the primary and secondary smaller laminae. These were the primitive corneum
      papillae. From 205 days, the corneum papillae were present in all four sizes of
      laminae. The histodifferentiation of the lamina propia-submucosa, tunica
      muscularis and serosa showed patterns of development similar to those reported
      for the rumen and reticulum of red deer. The omasum of red deer during prenatal
      life, especially from 67 days of gestation, was shown to be an active structure
      with full secretory capacity. Its histological development, its secretory
      capacity (detected by the presence of neutral mucopolysaccharides) and its
      neuroendocrine nature (detected by the presence of positive non-neuronal enolase
      cells and the neuropeptides vasoactive intestinal peptide and neuropeptide Y)
      were parallel to the development of the rumen and the reticulum. However, its
      prenatal development was later than that of the omasum in sheep, goat and cow.

PMID- 15960766
TI  - Functional specialisation of pelvic limb anatomy in horses (Equus caballus).
AB  - We provide quantitative anatomical data on the muscle-tendon units of the equine
      pelvic limb. Specifically, we recorded muscle mass, fascicle length, pennation
      angle, tendon mass and tendon rest length. Physiological cross sectional area was
      then determined and maximum isometric force estimated. There was proximal-to
      distal reduction in muscle volume and fascicle length. Proximal limb tendons were
      few and, where present, were relatively short. By contrast, distal limb tendons
      were numerous and long in comparison to mean muscle fascicle length, increasing
      potential for elastic energy storage. When compared with published data on
      thoracic limb muscles, proximal pelvic limb muscles were larger in volume and had
      shorter fascicles. Distal limb muscle architecture was similar in thoracic and
      pelvic limbs with the exception of flexor digitorum lateralis (lateral head of
      the deep digital flexor), the architecture of which was similar to that of the
      pelvic and thoracic limb superficial digital flexors, suggesting a functional
      similarity.

PMID- 15960767
TI  - Growth patterns of fresh human crystalline lenses measured by in vitro
      photographic biometry.
AB  - The purpose of the study was to demonstrate and evaluate the use of digital-image
      photography to measure the central thickness and equatorial diameter of whole
      fresh human crystalline lenses free of all zonular attachments. Forty-one human
      donor postmortem intact clear crystalline lenses, with a mean age of 28.5 +/-
      16.4 years, were obtained by the contributing eye banks. The lenses were removed
      by the eye bank and shipped in Optisol-GS, a physiologic preservative storage
      medium, at 7 degrees C. The lenses were stored at the same temperature and in the
      same preservative throughout this study. This medium has been demonstrated to
      maintain the morphometric characteristics of epithelial cells. After freeing the
      lenses of all residual zonular attachments, digital photographs were obtained
      within an average of 20.9 +/- 13.4 h after death. The digital images were used to
      determine the central thickness and equatorial diameter of the crystalline
      lenses. By carefully calibrating the digital images and maintaining the lenses in
      physiological storage medium, reliable dimensional measurements were obtained.
      The dimensions for central thickness for each lens were compared to published,
      age-matched lenses, measured in vivo, and were found to duplicate these in vivo
      measurements reliably.

PMID- 15960768
TI  - Contact guidance in human dermal fibroblasts is modulated by population pressure.
AB  - Morphogenesis is underpinned by orientated cell division, motility and growth.
      The substratum for migrating cells in vivo comprises either extracellular matrix
      or the surfaces of adjacent cells and both are believed to inform the dynamic
      behaviour of adherent cells through contact guidance. Collisions between
      migrating cells in vitro can induce the phenomena of contact inhibition of
      locomotion and division, suggesting that their sensitivity to substratum-derived
      cues may also be influenced by population density. In the present study dermal
      fibroblasts, which are known to be motile in culture and are fundamental to the
      organization of the extracellular matrix, were used to examine the influence of
      population pressure on the ability of substratum topography to induce contact
      guidance. The findings suggest that sensitivity to substratum-derived
      morphogenetic guidance cues, as revealed by alignment of cells to
      microtopography, is modulated by population pressure.

PMID- 15960769
TI  - One of these things is not like the others: the idea of precedence in health
      technology assessment and coverage decisions.
AB  - Health plans often deliberate covering technologies with challenging purposes,
      effects, or costs. They must integrate quantitative evidence (e.g., how well a
      technology works) with qualitative, normative assessments (e.g., whether it works
      well enough for a worthwhile purpose). Arguments from analogy and precedent help
      integrate these criteria and establish standards for their policy application.
      Examples of arguments are described for three technologies (ICSI, genetic tests,
      and Viagra). Drawing lessons from law, ethics, philosophy, and the social
      sciences, a framework is developed for case-based evaluation of new technologies.
      The decision-making cycle includes (1) taking stock of past decisions and
      formulating precedents, (2) deciding new cases, and (3) assimilating decisions
      into the case history and evaluation framework. Each stage requires distinctive
      decision maker roles, information, and methods.

PMID- 15960770
TI  - The common law power of the legislature: insurer conversions and charitable
      funds.
AB  - New York's Empire Blue Cross and Blue Shield conversion from nonprofit to for
      profit form has considerable legal significance. Three aspects of the conversion
      make the case unique: the role of the state legislature in directing the
      disposition of the conversion assets, the fact that it made itself the primary
      beneficiary of those assets, and the actions of the state attorney general
      defending the state rather than the public interest in the charitable assets.
      Drawing on several centuries of common law rejecting the legislative power to
      direct the disposition of charitable funds, this article argues that the
      legislature lacked power to control the conversion and direct the disposition of
      its proceeds and that its actions not only undermined the nonprofit form but also
      raised constitutional concerns.

PMID- 15960771
TI  - The politics of racial disparities: desegregating the hospitals in Jackson,
      Mississippi.
AB  - As health care policymakers and providers focus on eliminating the persistent
      racial disparities in treatment, it is useful to explore how resistance to
      hospital desegregation was overcome. Jackson, Mississippi, provides an
      instructive case study of how largely concealed deliberations achieved the
      necessary concessions in a still rigidly segregated community. The Veterans
      Administration hospital, the medical school hospital, and the private nonprofit
      facilities were successively desegregated, owing mainly to the threatened loss of
      federal dollars. Many of the changes, however, were cosmetic. In contrast to the
      powerful financial incentives offered to hospitals to desegregate and ensure
      equal access in the early years of the Medicare program, current trends in
      federal reimbursement encourage segregation and disparities in treatment.

PMID- 15960772
TI  - Mental health policy and psychotropic drugs.
AB  - The pace of innovation in psychotropic drugs has been rapid over the past 15
      years. There also have been unprecedented increases in spending on prescription
      drugs generally and psychotropic medications specifically. Psychotropic
      medications are playing a more central role in treatment. They also are receiving
      close scrutiny from health insurers, state budget makers, and ordinary citizens.
      Public policy actions regarding prescription drugs have the potential to
      significantly affect clinical care for mental disorders, the costs of this care
      to individuals and society at large, and the prospects for future scientific
      advances. This article outlines the policy issues related to psychotropic drugs
      with respect to their role in determining access to mental health treatment and
      the cost and quality of mental health care.

PMID- 15960773
TI  - Consulting as a strategy for knowledge transfer.
AB  - Academic researchers who work on health policy and health services are expected
      to transfer knowledge to decision makers. Decision makers often do not, however,
      regard academics' traditional ways of doing research and disseminating their
      findings as relevant or useful. This article argues that consulting can be a
      strategy for transferring knowledge between researchers and decision makers and
      is effective at promoting the "enlightenment" and "interactive" models of
      knowledge use. Based on three case studies, it develops a model of knowledge
      transfer-focused consulting that consists of six stages and four types of work.
      Finally, the article explores how knowledge is generated in consulting and
      identifies several classes of factors facilitating its use by decision makers.

PMID- 15960775
TI  - Dyslipidaemia in type 2 diabetes: effects of the thiazolidinediones pioglitazone
      and rosiglitazone.

PMID- 15960776
TI  - Home blood glucose monitoring in type 2 diabetes.

PMID- 15960777
TI  - Clinical networks in diabetes.

PMID- 15960778
TI  - Competency-based education and assessment, the route to competent healthcare
      professionals.

PMID- 15960780
TI  - Outcomes-based education for a changing health service.

PMID- 15960781
TI  - Clinical skills centres: where are we going?

PMID- 15960782
TI  - Lay participation in medical school curriculum development: whose problem is it?

PMID- 15960783
TI  - The future is flexible?

PMID- 15960784
TI  - Lessons for curriculum development and for education in caring for older people:
      the AAMC-Hartford Geriatrics Curriculum Program.

PMID- 15960785
TI  - Using a diary to quantify learning activities.
AB  - BACKGROUND: Diaries of actual learning activities can fill the gap between the
      planned curriculum and students' opinions and outcomes. We report the development
      and validity of such a method, estimate sources of variation and model sampling
      strategies to determine efficient ways to obtain information about a curriculum
      or about individual students. METHODS: Following development and piloting, the
      diary was administered to fourth- and fifth-year medical students. Each student
      was asked to complete a diary on 3 randomly selected days of the academic year.
      Sources of variance and generalisability were determined using variance
      components analysis. Validity was explored by comparing activities with what is
      known about the curriculum, assessment, timetables and the 2 classes of students.
      RESULTS: Response rate was 83% (287/345). Learning activities varied as expected
      with timing of assessments, and on weekdays compared with weekends. For most
      activities, 14 days per student would be needed to obtain generalisable
      information about an individual student. The variation between days is greater
      than the variation between students, meaning that sampling for information on a
      curriculum should include all students and all days of the year but the number of
      diaries per student could be kept low depending on the desired power to detect
      any differences. CONCLUSION: Such an evaluation method is feasible and can
      provide reliable and valid information about study activities. Reasons for good
      compliance are discussed. Sampling strategies should be tailored to the purpose
      of the study.

PMID- 15960786
TI  - Change in knowledge and skills of Year 3 undergraduates in evidence-based
      medicine seminars.
AB  - PURPOSE: To evaluate the effect of a compulsory evidence-based medicine (EBM)
      seminar in critical appraisal skills and the overall acceptance of compulsory EBM
      seminars for Year 3 medical undergraduate students. METHODS: Small group seminars
      by peer teaching were conducted for up to 23 undergraduates. Knowledge and skills
      in EBM before and after the compulsory seminars were evaluated by 2 different
      sets of 20 questions. To apply knowledge, each undergraduate had to analyse an
      individual paper case using the principles of EBM. Undergraduates gave anonymous
      feedback using separate evaluation sheets at the end of the seminar. Main outcome
      variables were changes in knowledge and skills. RESULTS: A total of 132 Year 3
      undergraduates at the University of Frankfurt participated in a compulsory EBM
      seminar during the academic half-year 2003/04 as part of their regular
      curriculum. Complete datasets were available for evaluation from 124
      undergraduates (94%). The seminars led to an overall increase in knowledge
      (question paper score increase from 2.37 to 7.48, 99% CI 6.61-8.36, or 216%).
      Transfer of knowledge into a paper case scenario was generally good, with a mean
      score of 49.5 (SD 5.24) out of 55 points. Feedback indicated good overall
      acceptance of the seminars, with a median of 2 (score range from 1 = excellent to
      6 = failed). CONCLUSION: Trained medical students are effective and well accepted
      EBM trainers in compulsory undergraduate seminars.

PMID- 15960787
TI  - Independent student study groups.
AB  - BACKGROUND AND OBJECTIVES: Teachers and students regulate learning to varying
      degrees in educational programmes in higher education. We present evidence that
      students in a student-centred medical programme self- and co-regulate their
      learning in independently formed study groups. We describe the perceived benefits
      of study groups and the effect of study group membership on student achievement.
      SETTING: Years 1-2 of a 4-year, graduate-entry problem-based medical programme.
      METHODS: We surveyed 233 year 2 students about features of their study groups and
      their study group membership in years 1-2. We compared study group membership
      with students' scores on a written summative assessment held at the end of their
      second year. RESULTS: For students who joined 1 study group, the length of time
      their group stayed together was positively related to achievement in the written
      summative assessment. There were no differences in summative assessment results
      between students who had been in a study group and students who had not been in a
      study group. CONCLUSION: Effective study groups are supportive, socially cohesive
      groups who generate mutual trust and loyalty, and self- and co-regulate their
      learning by giving and receiving explanations and summaries and motivating
      individual study. Teachers can support the formation of study groups by using
      small-group teaching/learning activities, providing clear learning outcomes and
      assessment criteria, minimising competition for grades and allocating room space.

PMID- 15960788
TI  - Developing an outcome-focused core curriculum.
AB  - BACKGROUND: Many UK medical schools have modified their curricula to meet the
      requirements of the General Medical Council and other external agencies. In
      particular, efforts have been focused on increasing integration and reducing
      factual overload through the definition of a core curriculum. Various approaches
      to curriculum change have been adopted in an attempt to meet such demands.
      PURPOSE: This paper describes a curriculum development process, which commences
      with a clear vision, adopts an outcome-based approach and identifies clear
      statements of learning outcomes. The process led to the development of an outcome
      focused core curriculum structured around clinical problems, which is available
      to all students and staff. CONCLUSION: A model of curriculum development has
      evolved which is relatively simple in concept, and appears to be easy to
      comprehend by students, teaching staff and visitors from other institutions. It
      provides a practical framework for managing the difficult problems of integration
      and factual overload. It should be of general interest and applicability to other
      schools with health professional programmes looking for a realistic and
      acceptable way of defining a core curriculum.

PMID- 15960789
TI  - A survey of staff attitudes to increasing medical undergraduate education in a
      district general hospital.
AB  - INTRODUCTION: Medical student numbers in Britain are increasing rapidly, beyond
      the capacity of most teaching hospitals, with more clinical teaching taking place
      in district general hospitals (DGHs). Surveys show that students value the
      intensive clinical teaching, smaller student numbers and perceived greater
      friendliness in DGHs. This paper explores DGH staff attitudes to teaching--their
      level of initial enthusiasm, their attitudes to current teaching, its effect on
      the hospital and to the sustainability of DGH undergraduate teaching--as both
      student numbers and service workloads continue to rise. METHODS: Semi-structured
      interviews with 6 key informants were used to generate themes for a 19-question
      pre-piloted anonymous postal questionnaire sent to all 68 staff involved in
      undergraduate medical teaching in Northampton General Hospital. RESULTS: The
      total response included 85% of consultants. Responses in the 3 staff groups were
      similar. Most respondents felt enthusiastic at the prospect of medical students,
      although they realised that this would be intellectually challenging and increase
      time pressures. These predictions were largely fulfilled. Respondents felt that
      in comparison to teaching hospitals the DGH teaching was more clinically based
      and consultant-led, with more approachable staff. Currently 41 respondents (82%)
      felt that they had inadequate teaching time. A majority felt that the arrival of
      students had improved patient care and that their department had benefited.
      Thirty-seven responders (74%) felt that the planned doubling of student numbers
      would impose an unsustainable departmental load, and would compromise teaching
      quality. The change felt most necessary to support additional teaching was
      increased clinical medical staff. Better co-ordination between the DGH and the
      medical school was also felt necessary. The most popular choice for the
      distribution of extra teaching finance was to the teacher's directorate, i.e.
      speciality [33 (66%)]. Forty-four (86%) felt that increased student numbers would
      have a significant impact on the character of the hospital. The 108 free-text
      comments (2.1 per respondent) centred on hospital character and the benefits of
      students. CONCLUSIONS: This study shows a considerable initial enthusiasm for
      teaching in DGH staff, which is persisting despite increasing student numbers.
      However, the current teaching load is seen to be substantial. Teaching more
      students is likely to produce major problems, based on lack of teaching time and
      increasingly heavy service commitments rather than lack of patients. This is
      likely to be a widespread problem for DGHs. Failure to ensure adequate teaching
      staff and facilities as well as co-ordination could threaten the sustainability
      of this potentially valuable teaching initiative.

PMID- 15960790
TI  - How medical residents perceive the quality of supervision provided by attending
      doctors in the clinical setting.
AB  - INTRODUCTION: The supervision of medical residents is a key responsibility of
      attending doctors in the clinical setting. Most attending doctors, however, are
      unfamiliar with the principles of effective supervision. Although inconsistent,
      supervision has been shown to be both important and effective for the
      professional development of medical residents. OBJECTIVE: To examine how medical
      residents perceive the supervisory roles of attending doctors, in terms of what
      they perceive as poor supervision and what they characterise as good supervisory
      practice. METHOD: We carried out a questionnaire survey of 38 medical residents
      at the Department of Paediatrics at the teaching hospital of the University of
      Amsterdam, the Netherlands. Attending doctors directly involved with the
      supervision of medical residents participated in the study. The clinical settings
      where supervision occurred included the neonatal and paediatric intensive care
      units and the general paediatric wards. RESULTS: Medical residents rated the
      quality of supervision they received in all departments positively. A majority of
      the attending doctors were rated highly in 'overall supervision'. Creating
      pleasant learning environments and being stimulated to learn and function
      independently were aspects of supervision characterised positively. Coaching in
      clinical skills and procedures, effective communication skills and clinical
      decision making using principles of cost-appropriate care were aspects of
      supervision found to be deficient. DISCUSSION: This study shows that medical
      residents enjoy supervision from collaborative, understanding and patient
      attending doctors. Medical residents prefer to be treated as adult learners and
      enjoy feedback that is constructive, measured and adapted to their professional
      needs.

PMID- 15960791
TI  - Students' opinions about their preparation for clinical practice.
AB  - INTRODUCTION: There are data that suggest that medical students do not feel
      sufficiently prepared for clinical practice in the clerkships. The transition
      from pre-clinical to clinical training causes problems. OBJECTIVES: To seek
      quantitative verification of qualitative findings from an earlier focus group
      study on problems medical students encounter when entering the clinical phase of
      undergraduate training. METHODS: At the start of the clinical phase, all Year 4
      students at Maastricht Medical School were surveyed on the transition from pre
      clinical to clinical training and its effects on workload, knowledge, skills and
      learning. RESULTS: The response rate was 67%. Students were uncertain as to how
      to behave and act, mainly because they did not know what was expected of them.
      They experienced a drastic increase in workload and a lack of time for studying.
      They considered themselves to be moderately prepared with regard to knowledge and
      they regarded their physical examination skills as satisfactory. Students
      reported having difficulty applying theoretical knowledge in clinical practice
      and perceived shortcomings in basic science knowledge. In addition, they felt
      compelled to change their learning strategies. DISCUSSION: The results of this
      study confirm the findings of the focus group study. The students experienced
      problems related to professional socialisation and workload and deficiencies in
      knowledge and the organisation of knowledge. A good starting point for
      improvement may involve exploring students' suggestions of an extensive
      introduction into the clerkships, a more gradual transition with regard to
      workload and closer integration of pre-clinical and clinical education.

PMID- 15960792
TI  - Peer assessment of professional competence.
AB  - BACKGROUND: Current assessment formats for medical students reliably test core
      knowledge and basic skills. Methods for assessing other important domains of
      competence, such as interpersonal skills, humanism and teamwork skills, are less
      well developed. This study describes the development, implementation and results
      of peer assessment as a measure of professional competence of medical students to
      be used for formative purposes. METHODS: Year 2 medical students assessed the
      professional competence of their peers using an online assessment instrument.
      Fifteen randomly selected classmates were assigned to assess each student. The
      responses were analysed to determine the reliability and validity of the scores
      and to explore relationships between peer assessments and other assessment
      measures. RESULTS: Factor analyses suggest a 2-dimensional conceptualisation of
      professional competence: 1 factor represents Work Habits, such as preparedness
      and initiative, and the other factor represents Interpersonal Habits, including
      respect and trustworthiness. The Work Habits factor had moderate, yet
      statistically significant correlations ranging from 0.21 to 0.53 with all other
      performance measures that were part of a comprehensive assessment of professional
      competence. Approximately 6 peer raters were needed to achieve a generalisability
      coefficient of 0.70. CONCLUSIONS: Our findings suggest that it is possible to
      introduce peer assessment for formative purposes in an undergraduate medical
      school programme that provides multiple opportunities to interact with and
      observe peers.

PMID- 15960793
TI  - A structured assessment of newly qualified medical graduates.
AB  - INTRODUCTION: While there is extensive published experience with the assessment
      of procedural skills in undergraduate students, this is limited in newly
      qualified medical graduates at the time of entry to the pre-registration
      (internship) year. The few studies that have been published suggest that these
      skills are frequently deficient when objectively tested. We therefore chose to
      assess the competence of a group of South African medical graduates on entry to
      their pre-registration year. METHODS: A total of 58 graduates of South African
      medical schools were assessed. Each subject participated in a 7-station objective
      structured clinical examination (OSCE); 6 of these assessed individual competence
      in phlebotomy, intramuscular injection, female pelvic examination, bladder
      catheterisation, tracheal intubation and prescription writing, while competence
      in cardiopulmonary resuscitation was assessed in a seventh station in randomly
      allocated teams of 3 candidates. Candidates' opinions of their own competence was
      sought by questionnaire. RESULTS: There was a wide variation in competence
      between subjects and across the range of tasks studied. Mean scores ranged from
      85.4% for phlebotomy to 55.3% for prescription writing. The average score across
      all stations was 67.5%, and no student obtained an overall cut-off score of 85%
      or more, which was established using a modified Angoff method. Subjects'
      assessment of their own performance was unduly optimistic; most believed that
      they had demonstrated competence despite clear shortcomings in technique.
      Objective scores for subjects who had been exposed to a structured skills
      laboratory programme were not significantly higher than for those who had not,
      although their self-assessed performance was indeed higher. DISCUSSION: Most of
      the South African medical graduates who participated in this study were unable to
      satisfactorily perform technical procedures appropriate to the house officer on
      entry to the pre-registration year. This is in line with the conclusions of the
      few studies published in other countries. We suggest that the learning outcomes
      of undergraduate medical programmes should include an explicit statement of the
      competencies required for practice in the pre-registration year, and that these
      should be adequately taught and rigorously assessed before graduation.

PMID- 15960794
TI  - Problem-based learning: future challenges for educational practice and research.
AB  - CONTEXT: Problem-based learning (PBL) is widely used in higher education. There
      is evidence available that students and faculty are highly satisfied with PBL.
      Nevertheless, in educational practice problems are often encountered, such as
      tutors who are too directive, problems that are too well-structured, and
      dysfunctional tutorial groups. PURPOSE: The aim of this paper is to demonstrate
      that PBL has the potential to prepare students more effectively for future
      learning because it is based on four modern insights into learning: constructive,
      self-directed, collaborative and contextual. These four learning principles are
      described and it is explained how they apply to PBL. In addition, available
      research is reviewed and the current debate in research on PBL is described.
      DISCUSSION: It is argued that problems encountered in educational practice
      usually stem from poor implementation of PBL. In many cases the way in which PBL
      is implemented is not consistent with the current insights on learning.
      Furthermore, it is argued that research on PBL should contribute towards a better
      understanding of why and how the concepts of constructive, self-directed,
      collaborative and contextual learning work or do not work and under what
      circumstances. Examples of studies are given to illustrate this issue.

PMID- 15960795
TI  - Making sense of focus groups.
AB  - CONTEXT: This paper provides an overview of the contribution of medical education
      research which has employed focus group methodology to evaluate both
      undergraduate education and continuing professional development. PRACTICALITIES
      AND PROBLEMS: It also examines current debates about the ethics and
      practicalities involved in conducting focus group research. It gives guidance as
      to how to go about designing and planning focus group studies, highlighting
      common misconceptions and pitfalls, emphasising that most problems stem from
      researchers ignoring the central assumptions which underpin the qualitative
      research endeavour. PRESENTING AND DEVELOPING FOCUS GROUP RESEARCH: Particular
      attention is paid to analysis and presentation of focus group work and the uses
      to which such information is put. Finally, it speculates about the future of
      focus group research in general and research in medical education in particular.

PMID- 15960796
TI  - Paired lecturing by a basic medical scientist and a clinician.

PMID- 15960797
TI  - Medical students' motivation.

PMID- 15960800
TI  - Mechanisms of aging in senescence-accelerated mice.
AB  - BACKGROUND: Progressive neurological dysfunction is a key aspect of human aging.
      Because of underlying differences in the aging of mice and humans, useful mouse
      models have been difficult to obtain and study. We have used gene-expression
      analysis and polymorphism screening to study molecular senescence of the retina
      and hippocampus in two rare inbred mouse models of accelerated neurological
      senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in
      a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J).
      RESULTS: The majority of age-related gene expression changes were strain
      specific, with only a few common pathways found for normal and accelerated
      neurological aging. Polymorphism screening led to the identification of mutations
      that could have a direct impact on important disease processes, including a
      mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic
      expression of the gene for the chemokine CCL19, which is involved in the
      inflammatory response. CONCLUSION: We show that combining the study of inbred
      mouse strains with interesting traits and gene-expression profiling can lead to
      the discovery of genes important for complex phenotypes. Furthermore, full-genome
      polymorphism detection, sequencing and gene-expression profiling of inbred mouse
      strains with interesting phenotypic differences may provide unique insights into
      the molecular genetics of late-manifesting complex diseases.

PMID- 15960801
TI  - Large-scale 13C-flux analysis reveals mechanistic principles of metabolic network
      robustness to null mutations in yeast.
AB  - BACKGROUND: Quantification of intracellular metabolite fluxes by 13C-tracer
      experiments is maturing into a routine higher-throughput analysis. The question
      now arises as to which mutants should be analyzed. Here we identify key
      experiments in a systems biology approach with a genome-scale model of
      Saccharomyces cerevisiae metabolism, thereby reducing the workload for
      experimental network analyses and functional genomics. RESULTS: Genome-scale 13C
      flux analysis revealed that about half of the 745 biochemical reactions were
      active during growth on glucose, but that alternative pathways exist for only 51
      gene-encoded reactions with significant flux. These flexible reactions identified
      in silico are key targets for experimental flux analysis, and we present the
      first large-scale metabolic flux data for yeast, covering half of these mutants
      during growth on glucose. The metabolic lesions were often counteracted by flux
      rerouting, but knockout of cofactor-dependent reactions, as in the adh1, ald6,
      cox5A, fum1, mdh1, pda1, and zwf1 mutations, caused flux responses in more
      distant parts of the network. By integrating computational analyses, flux data,
      and physiological phenotypes of all mutants in active reactions, we quantified
      the relative importance of 'genetic buffering' through alternative pathways and
      network redundancy through duplicate genes for genetic robustness of the network.
      CONCLUSIONS: The apparent dispensability of knockout mutants with metabolic
      function is explained by gene inactivity under a particular condition in about
      half of the cases. For the remaining 207 viable mutants of active reactions,
      network redundancy through duplicate genes was the major (75%) and alternative
      pathways the minor (25%) molecular mechanism of genetic network robustness in S.
      cerevisiae.

PMID- 15960802
TI  - The rarity of gene shuffling in conserved genes.
AB  - BACKGROUND: Among three sources of evolutionary innovation in gene function -
      point mutations, gene duplications, and gene shuffling (recombination between
      dissimilar genes) - gene shuffling is the most potent one. However, surprisingly
      little is known about its incidence on a genome-wide scale. RESULTS: We have
      studied shuffling in genes that are conserved between distantly related species.
      Specifically, we estimated the incidence of gene shuffling in ten organisms from
      the three domains of life: eukaryotes, eubacteria, and archaea, considering only
      genes showing significant sequence similarity in pairwise genome comparisons. We
      found that successful gene shuffling is very rare among such conserved genes. For
      example, we could detect only 48 successful gene-shuffling events in the genome
      of the fruit fly Drosophila melanogaster which have occurred since its common
      ancestor with the worm Caenorhabditis elegans more than half a billion years ago.
      CONCLUSION: The incidence of gene shuffling is roughly an order of magnitude
      smaller than the incidence of single-gene duplication in eukaryotes, but it can
      approach or even exceed the gene-duplication rate in prokaryotes. If true in
      general, this pattern suggests that gene shuffling may not be a major force in
      reshaping the core genomes of eukaryotes. Our results also cast doubt on the
      notion that introns facilitate gene shuffling, both because prokaryotes show an
      appreciable incidence of gene shuffling despite their lack of introns and because
      we find no statistical association between exon-intron boundaries and recombined
      domains in the two multicellular genomes we studied.

PMID- 15960803
TI  - Natural antisense transcripts with coding capacity in Arabidopsis may have a
      regulatory role that is not linked to double-stranded RNA degradation.
AB  - BACKGROUND: Overlapping transcripts in antisense orientation have the potential
      to form double-stranded RNA (dsRNA), a substrate for a number of different RNA
      modification pathways. One prominent route for dsRNA is its breakdown by Dicer
      enzyme complexes into small RNAs, a pathway that is widely exploited by RNA
      interference technology to inactivate defined genes in transgenic lines. The
      significance of this pathway for endogenous gene regulation remains unclear.
      RESULTS: We have examined transcription data for overlapping gene pairs in
      Arabidopsis thaliana. On the basis of an analysis of transcripts with coding
      regions, we find the majority of overlapping gene pairs to be convergently
      overlapping pairs (COPs), with the potential for dsRNA formation. In all tissues,
      COP transcripts are present at a higher frequency compared to the overall gene
      pool. The probability that both the sense and antisense copy of a COP are co
      transcribed matches the theoretical value for coexpression under the assumption
      that the expression of one partner does not affect the expression of the other.
      Among COPs, we observe an over-representation of spliced (intron-containing)
      genes (90%) and of genes with alternatively spliced transcripts. For loci where
      antisense transcripts overlap with sense transcript introns, we also find a
      significant bias in favor of alternative splicing and variation of
      polyadenylation. CONCLUSION: The results argue against a predominant RNA
      degradation effect induced by dsRNA formation. Instead, our data support
      alternative roles for dsRNAs. They suggest that at least for a subgroup of COPs,
      antisense expression may induce alternative splicing or polyadenylation.

PMID- 15960804
TI  - Tiling microarray analysis of rice chromosome 10 to identify the transcriptome
      and relate its expression to chromosomal architecture.
AB  - BACKGROUND: Sequencing and annotation of the genome of rice (Oryza sativa) have
      generated gene models in numbers that top all other fully sequenced species, with
      many lacking recognizable sequence homology to known genes. Experimental
      evaluation of these gene models and identification of new models will facilitate
      rice genome annotation and the application of this knowledge to other more
      complex cereal genomes. RESULTS: We report here an analysis of the chromosome 10
      transcriptome of the two major rice subspecies, japonica and indica, using
      oligonucleotide tiling microarrays. This analysis detected expression of
      approximately three-quarters of the gene models without previous experimental
      evidence in both subspecies. Cloning and sequence analysis of the previously
      unsupported models suggests that the predicted gene structure of nearly half of
      those models needs improvement. Coupled with comparative gene model mapping, the
      tiling microarray analysis identified 549 new models for the japonica chromosome,
      representing an 18% increase in the annotated protein-coding capacity.
      Furthermore, an asymmetric distribution of genome elements along the chromosome
      was found that coincides with the cytological definition of the heterochromatin
      and euchromatin domains. The heterochromatin domain appears to associate with
      distinct chromosome level transcriptional activities under normal and stress
      conditions. CONCLUSION: These results demonstrated the utility of genome tiling
      microarray in evaluating annotated rice gene models and in identifying novel
      transcriptional units. The tiling microarray sanalysis further revealed a
      chromosome-wide transcription pattern that suggests a role for transposable
      element-enriched heterochromatin in shaping global transcription in response to
      environmental changes in rice.

PMID- 15960805
TI  - Identification of co-regulated transcripts affecting male body size in
      Drosophila.
AB  - Factor analysis is an analytic approach that describes the covariation among a
      set of genes through the estimation of 'factors', which may be, for example,
      transcription factors, microRNAs (miRNAs), and so on, by which the genes are co
      regulated. Factor analysis gives a direct mechanism by which to relate gene
      networks to complex traits. Using simulated data, we found that factor analysis
      clearly identifies the number and structure of factors and outperforms
      hierarchical cluster analysis. Noise genes, genes that are not correlated with
      any factor, can be distinguished even when factor structure is complex. Applied
      to body size in Drosophila simulans, an evolutionarily important complex trait, a
      factor was directly associated with body size.

PMID- 15960806
TI  - Single-feature polymorphism discovery in the barley transcriptome.
AB  - A probe-level model for analysis of GeneChip gene-expression data is presented
      which identified more than 10,000 single-feature polymorphisms (SFP) between two
      barley genotypes. The method has good sensitivity, as 67% of known single
      nucleotide polymorphisms (SNP) were called as SFPs. This method is applicable to
      all oligonucleotide microarray data, accounts for SNP effects in gene-expression
      data and represents an efficient and versatile approach for highly parallel
      marker identification in large genomes.

PMID- 15960808
TI  - How may you help me?
AB  - Most of us have had so many bad experiences with service personnel over the years
      that we harbor the illusion that doing things for ourselves is faster and better.

PMID- 15960807
TI  - Refinement and prediction of protein prenylation motifs.
AB  - We refined the motifs for carboxy-terminal protein prenylation by analysis of
      known substrates for farnesyltransferase (FT), geranylgeranyltransferase I (GGT1)
      and geranylgeranyltransferase II (GGT2). In addition to the CaaX box for the
      first two enzymes, we identify a preceding linker region that appears constrained
      in physicochemical properties, requiring small or flexible, preferably
      hydrophilic, amino acids. Predictors were constructed on the basis of sequence
      and physical property profiles, including interpositional correlations, and are
      available as the Prenylation Prediction Suite (PrePS,
      http://mendel.imp.univie.ac.at/sat/PrePS) which also allows evaluation of
      evolutionary motif conservation. PrePS can predict partially overlapping
      substrate specificities, which is of medical importance in the case of
      understanding cellular action of FT inhibitors as anticancer and anti-parasite
      agents.

PMID- 15960809
TI  - Biochip sensors for the rapid and sensitive detection of viral disease.
AB  - Recent advances in DNA and protein microarray methodology and the emerging
      technology of cell-based sensors have massively increased the speed and
      sensitivity with which we can detect viral infections. The advantages of the
      multi-parameter microarray technologies could be combined with the speed and
      sensitivity of cell-based systems to give 'cell-omic' sensors.

PMID- 15960810
TI  - Histone modifications: from genome-wide maps to functional insights.
AB  - A large number of histone modifications has been implicated in the regulation of
      gene expression. Together, these modifications have the potential to form a
      complex combinatorial regulatory code. Genome-wide mapping approaches provide new
      opportunities to decipher this code, but they may suffer from systematic biases.
      Integration of datasets and improved technologies will provide the way forward.

PMID- 15960811
TI  - Making sense of nonsense: the evolution of selenocysteine usage in proteins.
AB  - A recent analysis of sequences derived from organisms in the Sargasso Sea has
      revealed a surprisingly different set of selenium-containing proteins than that
      previously found in sequenced genomes and suggests that selenocysteine
      utilization has been lost by many groups of organisms during evolution.

PMID- 15960812
TI  - The Dictyostelium genome: the private life of a social model revealed?
AB  - The complete genome sequence of Dictyostelium, a widely studied social amoeba,
      reveals unexpected complexities in genome structure, and cell motility and
      signaling, most notably the presence of a large number of G-protein-coupled
      receptors not previously found outside animals and the absence of receptor
      tyrosine kinases.

PMID- 15960814
TI  - Plant and animal genomes achieve functionality.
AB  - A report on the conference 'Plant and Animal Genomes XIII', San Diego, USA, 15-19
      January 2005.

PMID- 15960813
TI  - The B7 family of immune-regulatory ligands.
AB  - The B7 family consists of structurally related, cell-surface protein ligands,
      which bind to receptors on lymphocytes that regulate immune responses. Activation
      of T and B lymphocytes is initiated by engagement of cell-surface, antigen
      specific T-cell receptors or B-cell receptors, but additional signals delivered
      simultaneously by B7 ligands determine the ultimate immune response. These
      'costimulatory' or 'coinhibitory' signals are delivered by B7 ligands through the
      CD28 family of receptors on lymphocytes. Interaction of B7-family members with
      costimulatory receptors augments immune responses, and interaction with
      coinhibitory receptors attenuates immune responses. There are currently seven
      known members of the family: B7.1 (CD80), B7.2 (CD86), inducible costimulator
      ligand (ICOS-L), programmed death-1 ligand (PD-L1), programmed death-2 ligand (PD
      L2), B7-H3, and B7-H4. Members of the family have been characterized
      predominantly in humans and mice, but some members are also found in birds. They
      share 20-40% amino-acid identity and are structurally related, with the
      extracellular domain containing tandem domains related to variable and constant
      immunoglobulin domains. B7 ligands are expressed in lymphoid and non-lymphoid
      tissues. The importance of the family in regulating immune responses is shown by
      the development of immunodeficiency and autoimmune diseases in mice with
      mutations in B7-family genes. Manipulation of the signals delivered by B7 ligands
      has shown potential in the treatment of autoimmunity, inflammatory diseases and
      cancer.

PMID- 15960815
TI  - Biocomputing enters its adolescence.
AB  - A report on the tenth Pacific Symposium on Biocomputing, Big Island, Hawaii, USA,
      4-8 January 2005.

PMID- 15960817
TI  - B cell targeted therapies.
AB  - Although the precise pathogenesis of rheumatoid arthritis (RA) remains unclear,
      many cell populations, including monocytes, macrophages, endothelial cells,
      fibroblasts and B cells, participate in the inflammatory process. Ongoing
      research continues to evaluate the critical roles played by B cells in sustaining
      the chronic inflammatory process of RA. These findings have contributed to the
      development of targeted therapies that deplete B cells, such as rituximab, as
      well as inhibitors of B lymphocyte stimulation, such as belimumab. In a phase I
      trial, belimumab treatment significantly reduced CD20+ levels in patients with
      systemic lupus erythematosus. Phase I and phase II trials of rituximab found that
      rituximab plus methotrexate achieved significantly better American College of
      Rheumatology 50% responses for patients with RA than those patients receiving
      monotherapy with methotrexate. These clinical trial data present promising
      evidence for B cell targeted therapies as future therapeutic options for RA.

PMID- 15960818
TI  - B cell non-Hodgkin's lymphoma: rituximab safety experience.
AB  - A substantial body of data supports use of rituximab as first-line and
      maintenance therapy for the treatment of indolent non-Hodgkin's lymphoma. With 7
      years of postmarketing surveillance experience and more than 370,000 patient
      exposures, the safety profile of rituximab is well defined. Several multicenter
      trials suggest that infusion reactions associated with rituximab administration
      are well characterized and generally associated with the first infusion; toxicity
      is reduced with subsequent doses. Since some adverse events are related to
      circulating tumor loads of non-Hodgkin's lymphoma, fewer events are anticipated
      in rheumatoid arthritis. Low infection rates in oncology would indicate similar
      safety in patients with rheumatoid arthritis.

PMID- 15960819
TI  - Unmet needs in rheumatoid arthritis.
AB  - Until the pathophysiology/etiology of rheumatoid arthritis (RA) is better
      understood, treatment strategies must focus on disease management. Early
      diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) are
      necessary to reduce early joint damage, functional loss, and mortality. Several
      clinical trials have now clearly shown that administering appropriate DMARDs
      early yields better therapeutic outcomes. However, RA is a heterogeneous disease
      in which responses to treatment vary considerably for any given patient. Thus,
      choosing which patients receive combination DMARDs, and which combinations,
      remains one of our major challenges in treating RA patients. In many well
      controlled clinical trials methotrexate and other DMARDs, including the tumor
      necrosis factor-alpha inhibitors, have shown considerable efficacy in controlling
      the inflammatory process, but many patients continue to have active disease.
      Optimizing clinical response requires the use of a full spectrum of clinical
      agents with different therapeutic targets. Newer therapies, such as rituximab,
      that specifically target B cells have emerged as viable treatment options for
      patients with RA.

PMID- 15960820
TI  - B cells in rheumatoid synovitis.
AB  - In rheumatoid arthritis, T cells, B cells, macrophages, and dendritic cells
      invade the synovial membranes, establishing complex microstructures that promote
      inflammatory/tissue destructive lesions. B cell involvement has been considered
      to be limited to autoantibody production. However, recent studies suggest that B
      cells support rheumatoid disease through other mechanisms. A critical element of
      rheumatoid synovitis is the process of ectopic lymphoid neogenesis, with highly
      efficient lymphoid architectures established in a nonlymphoid tissue site.
      Rheumatoid synovitis recapitulates the pathways of lymph node formation, and B
      cells play a key role in this process. Furthermore, studies of rheumatoid lesions
      implanted in immunodeficient mice suggest that T cell activation in synovitis is
      B cell dependent, indicating the role played by B cells in presenting antigens
      and providing survival signals.

PMID- 15960821
TI  - Overview of BioCreAtIvE: critical assessment of information extraction for
      biology.
AB  - BACKGROUND: The goal of the first BioCreAtIvE challenge (Critical Assessment of
      Information Extraction in Biology) was to provide a set of common evaluation
      tasks to assess the state of the art for text mining applied to biological
      problems. The results were presented in a workshop held in Granada, Spain March
      28-31, 2004. The articles collected in this BMC Bioinformatics supplement
      entitled "A critical assessment of text mining methods in molecular biology"
      describe the BioCreAtIvE tasks, systems, results and their independent
      evaluation. RESULTS: BioCreAtIvE focused on two tasks. The first dealt with
      extraction of gene or protein names from text, and their mapping into
      standardized gene identifiers for three model organism databases (fly, mouse,
      yeast). The second task addressed issues of functional annotation, requiring
      systems to identify specific text passages that supported Gene Ontology
      annotations for specific proteins, given full text articles. CONCLUSION: The
      first BioCreAtIvE assessment achieved a high level of international participation
      (27 groups from 10 countries). The assessment provided state-of-the-art
      performance results for a basic task (gene name finding and normalization), where
      the best systems achieved a balanced 80% precision / recall or better, which
      potentially makes them suitable for real applications in biology. The results for
      the advanced task (functional annotation from free text) were significantly
      lower, demonstrating the current limitations of text-mining approaches where
      knowledge extrapolation and interpretation are required. In addition, an
      important contribution of BioCreAtIvE has been the creation and release of
      training and test data sets for both tasks. There are 22 articles in this special
      issue, including six that provide analyses of results or data quality for the
      data sets, including a novel inter-annotator consistency assessment for the test
      set used in task 2.

PMID- 15960822
TI  - Text detective: a rule-based system for gene annotation in biomedical texts.
AB  - BACKGROUND: The identification of mentions of gene or gene products in biomedical
      texts is a critical step in the development of text mining applications in
      biosciences. The complexity and ambiguity of gene nomenclature makes this a very
      difficult task. METHODS: Here we present a novel approach based on a combination
      of carefully designed rules and several lexicons of biological concepts,
      implemented in the Text Detective system. Text Detective is able to normalize the
      results of gene mentions found by offering the appropriate database reference.
      RESULTS: In BioCreAtIvE evaluation, Text Detective achieved results of 84%
      precision, 71% recall for task 1A, and 79% precision, 71% recall for mouse genes
      in task 1B.

PMID- 15960823
TI  - Overview of BioCreAtIvE task 1B: normalized gene lists.
AB  - BACKGROUND: Our goal in BioCreAtIve has been to assess the state of the art in
      text mining, with emphasis on applications that reflect real biological
      applications, e.g., the curation process for model organism databases. This paper
      summarizes the BioCreAtIvE task 1B, the "Normalized Gene List" task, which was
      inspired by the gene list supplied for each curated paper in a model organism
      database. The task was to produce the correct list of unique gene identifiers for
      the genes and gene products mentioned in sets of abstracts from three model
      organisms (Yeast, Fly, and Mouse). RESULTS: Eight groups fielded systems for
      three data sets (Yeast, Fly, and Mouse). For Yeast, the top scoring system (out
      of 15) achieved 0.92 F-measure (harmonic mean of precision and recall); for Mouse
      and Fly, the task was more difficult, due to larger numbers of genes, more
      ambiguity in the gene naming conventions (particularly for Fly), and complex gene
      names (for Mouse). For Fly, the top F-measure was 0.82 out of 11 systems and for
      Mouse, it was 0.79 out of 16 systems. CONCLUSION: This assessment demonstrates
      that multiple groups were able to perform a real biological task across a range
      of organisms. The performance was dependent on the organism, and specifically on
      the naming conventions associated with each organism. These results hold out
      promise that the technology can provide partial automation of the curation
      process in the near future.

PMID- 15960824
TI  - Data preparation and interannotator agreement: BioCreAtIvE task 1B.
AB  - BACKGROUND: We prepared and evaluated training and test materials for an
      assessment of text mining methods in molecular biology. The goal of the
      assessment was to evaluate the ability of automated systems to generate a list of
      unique gene identifiers from PubMed abstracts for the three model organisms Fly,
      Mouse, and Yeast. This paper describes the preparation and evaluation of answer
      keys for training and testing. These consisted of lists of normalized gene names
      found in the abstracts, generated by adapting the gene list for the full journal
      articles found in the model organism databases. For the training dataset, the
      gene list was pruned automatically to remove gene names not found in the
      abstract; for the testing dataset, it was further refined by manual annotation by
      annotators provided with guidelines. A critical step in interpreting the results
      of an assessment is to evaluate the quality of the data preparation. We did this
      by careful assessment of interannotator agreement and the use of answer pooling
      of participant results to improve the quality of the final testing dataset.
      RESULTS: Interannotator analysis on a small dataset showed that our gene lists
      for Fly and Yeast were good (87% and 91% three-way agreement) but the Mouse gene
      list had many conflicts (mostly omissions), which resulted in errors (69%
      interannotator agreement). By comparing and pooling answers from the participant
      systems, we were able to add an additional check on the test data; this allowed
      us to find additional errors, especially in Mouse. This led to 1% change in the
      Yeast and Fly "gold standard" answer keys, but to an 8% change in the mouse
      answer key. CONCLUSION: We found that clear annotation guidelines are important,
      along with careful interannotator experiments, to validate the generated gene
      lists. Also, abstracts alone are a poor resource for identifying genes in paper,
      containing only a fraction of genes mentioned in the full text (25% for Fly, 36%
      for Mouse). We found that there are intrinsic differences between the model
      organism databases related to the number of synonymous terms and also to curation
      criteria. Finally, we found that answer pooling was much faster and allowed us to
      identify more conflicting genes than interannotator analysis.

PMID- 15960825
TI  - Automatically annotating documents with normalized gene lists.
AB  - BACKGROUND: Document gene normalization is the problem of creating a list of
      unique identifiers for genes that are mentioned within a document. Automating
      this process has many potential applications in both information extraction and
      database curation systems. Here we present two separate solutions to this
      problem. The first is primarily based on standard pattern matching and
      information extraction techniques. The second and more novel solution uses a
      statistical classifier to recognize valid gene matches from a list of known gene
      synonyms. RESULTS: We compare the results of the two systems, analyze their
      merits and argue that the classification based system is preferable for many
      reasons including performance, simplicity and robustness. Our best systems attain
      a balanced precision and recall in the range of 74%-92%, depending on the
      organism.

PMID- 15960826
TI  - ProMiner: rule-based protein and gene entity recognition.
AB  - BACKGROUND: Identification of gene and protein names in biomedical text is a
      challenging task as the corresponding nomenclature has evolved over time. This
      has led to multiple synonyms for individual genes and proteins, as well as names
      that may be ambiguous with other gene names or with general English words. The
      Gene List Task of the BioCreAtIvE challenge evaluation enables comparison of
      systems addressing the problem of protein and gene name identification on common
      benchmark data. METHODS: The ProMiner system uses a pre-processed synonym
      dictionary to identify potential name occurrences in the biomedical text and
      associate protein and gene database identifiers with the detected matches. It
      follows a rule-based approach and its search algorithm is geared towards
      recognition of multi-word names. To account for the large number of ambiguous
      synonyms in the considered organisms, the system has been extended to use
      specific variants of the detection procedure for highly ambiguous and case
      sensitive synonyms. Based on all detected synonyms for one abstract, the most
      plausible database identifiers are associated with the text. Organism specificity
      is addressed by a simple procedure based on additionally detected organism names
      in an abstract. RESULTS: The extended ProMiner system has been applied to the
      test cases of the BioCreAtIvE competition with highly encouraging results. In
      blind predictions, the system achieved an F-measure of approximately 0.8 for the
      organisms mouse and fly and about 0.9 for the organism yeast.

PMID- 15960827
TI  - A simple approach for protein name identification: prospects and limits.
AB  - BACKGROUND: Significant parts of biological knowledge are available only as
      unstructured text in articles of biomedical journals. By automatically
      identifying gene and gene product (protein) names and mapping these to unique
      database identifiers, it becomes possible to extract and integrate information
      from articles and various data sources. We present a simple and efficient
      approach that identifies gene and protein names in texts and returns database
      identifiers for matches. It has been evaluated in the recent BioCreAtIvE entity
      extraction and mention normalization task by an independent jury. METHODS: Our
      approach is based on the use of synonym lists that map the unique database
      identifiers for each gene/protein to the different synonym names. For yeast and
      mouse, synonym lists were used as provided by the organizers who generated them
      from public model organism databases. The synonym list for fly was generated
      directly from the corresponding organism database. The lists were then
      extensively curated in largely automated procedure and matched against MEDLINE
      abstracts by exact text matching. Rule-based and support vector machine-based
      post filters were designed and applied to improve precision. RESULTS: Our
      procedure showed high recall and precision with F-measures of 0.897 for yeast and
      0.764/0.773 for mouse in the BioCreAtIvE assessment (Task 1B) and 0.768 for fly
      in a post-evaluation. CONCLUSION: The results were close to the best over all
      submissions. Depending on the synonym properties it can be crucial to consider
      context and to filter out erroneous matches. This is especially important for
      fly, which has a very challenging nomenclature for the protein name
      identification task. Here, the support vector machine-based post filter proved to
      be very effective.

PMID- 15960828
TI  - Evaluation of BioCreAtIvE assessment of task 2.
AB  - BACKGROUND: Molecular Biology accumulated substantial amounts of data concerning
      functions of genes and proteins. Information relating to functional descriptions
      is generally extracted manually from textual data and stored in biological
      databases to build up annotations for large collections of gene products. Those
      annotation databases are crucial for the interpretation of large scale analysis
      approaches using bioinformatics or experimental techniques. Due to the growing
      accumulation of functional descriptions in biomedical literature the need for
      text mining tools to facilitate the extraction of such annotations is urgent. In
      order to make text mining tools useable in real world scenarios, for instance to
      assist database curators during annotation of protein function, comparisons and
      evaluations of different approaches on full text articles are needed. RESULTS:
      The Critical Assessment for Information Extraction in Biology (BioCreAtIvE)
      contest consists of a community wide competition aiming to evaluate different
      strategies for text mining tools, as applied to biomedical literature. We report
      on task two which addressed the automatic extraction and assignment of Gene
      Ontology (GO) annotations of human proteins, using full text articles. The
      predictions of task 2 are based on triplets of protein--GO term--article passage.
      The annotation-relevant text passages were returned by the participants and
      evaluated by expert curators of the GO annotation (GOA) team at the European
      Institute of Bioinformatics (EBI). Each participant could submit up to three
      results for each sub-task comprising task 2. In total more than 15,000 individual
      results were provided by the participants. The curators evaluated in addition to
      the annotation itself, whether the protein and the GO term were correctly
      predicted and traceable through the submitted text fragment. CONCLUSION: Concepts
      provided by GO are currently the most extended set of terms used for annotating
      gene products, thus they were explored to assess how effectively text mining
      tools are able to extract those annotations automatically. Although the obtained
      results are promising, they are still far from reaching the required performance
      demanded by real world applications. Among the principal difficulties encountered
      to address the proposed task, were the complex nature of the GO terms and protein
      names (the large range of variants which are used to express proteins and
      especially GO terms in free text), and the lack of a standard training set. A
      range of very different strategies were used to tackle this task. The dataset
      generated in line with the BioCreative challenge is publicly available and will
      allow new possibilities for training information extraction methods in the domain
      of molecular biology.

PMID- 15960829
TI  - An evaluation of GO annotation retrieval for BioCreAtIvE and GOA.
AB  - BACKGROUND: The Gene Ontology Annotation (GOA) database http://www.ebi.ac.uk/GOA
      aims to provide high-quality supplementary GO annotation to proteins in the
      UniProt Knowledgebase. Like many other biological databases, GOA gathers much of
      its content from the careful manual curation of literature. However, as both the
      volume of literature and of proteins requiring characterization increases, the
      manual processing capability can become overloaded. Consequently, semi-automated
      aids are often employed to expedite the curation process. Traditionally,
      electronic techniques in GOA depend largely on exploiting the knowledge in
      existing resources such as InterPro. However, in recent years, text mining has
      been hailed as a potentially useful tool to aid the curation process. To
      encourage the development of such tools, the GOA team at EBI agreed to take part
      in the functional annotation task of the BioCreAtIvE (Critical Assessment of
      Information Extraction systems in Biology) challenge. BioCreAtIvE task 2 was an
      experiment to test if automatically derived classification using information
      retrieval and extraction could assist expert biologists in the annotation of the
      GO vocabulary to the proteins in the UniProt Knowledgebase. GOA provided the
      training corpus of over 9000 manual GO annotations extracted from the literature.
      For the test set, we provided a corpus of 200 new Journal of Biological Chemistry
      articles used to annotate 286 human proteins with GO terms. A team of experts
      manually evaluated the results of 9 participating groups, each of which provided
      highlighted sentences to support their GO and protein annotation predictions.
      Here, we give a biological perspective on the evaluation, explain how we annotate
      GO using literature and offer some suggestions to improve the precision of future
      text-retrieval and extraction techniques. Finally, we provide the results of the
      first inter-annotator agreement study for manual GO curation, as well as an
      assessment of our current electronic GO annotation strategies. RESULTS: The GOA
      database currently extracts GO annotation from the literature with 91 to 100%
      precision, and at least 72% recall. This creates a particularly high threshold
      for text mining systems which in BioCreAtIvE task 2 (GO annotation extraction and
      retrieval) initial results precisely predicted GO terms only 10 to 20% of the
      time. CONCLUSION: Improvements in the performance and accuracy of text mining for
      GO terms should be expected in the next BioCreAtIvE challenge. In the meantime
      the manual and electronic GO annotation strategies already employed by GOA will
      provide high quality annotations.

PMID- 15960830
TI  - Learning statistical models for annotating proteins with function information
      using biomedical text.
AB  - BACKGROUND: The BioCreative text mining evaluation investigated the application
      of text mining methods to the task of automatically extracting information from
      text in biomedical research articles. We participated in Task 2 of the
      evaluation. For this task, we built a system to automatically annotate a given
      protein with codes from the Gene Ontology (GO) using the text of an article from
      the biomedical literature as evidence. METHODS: Our system relies on simple
      statistical analyses of the full text article provided. We learn n-gram models
      for each GO code using statistical methods and use these models to hypothesize
      annotations. We also learn a set of Naive Bayes models that identify textual
      clues of possible connections between the given protein and a hypothesized
      annotation. These models are used to filter and rank the predictions of the n
      gram models. RESULTS: We report experiments evaluating the utility of various
      components of our system on a set of data held out during development, and
      experiments evaluating the utility of external data sources that we used to learn
      our models. Finally, we report our evaluation results from the BioCreative
      organizers. CONCLUSION: We observe that, on the test data, our system performs
      quite well relative to the other systems submitted to the evaluation. From other
      experiments on the held-out data, we observe that (i) the Naive Bayes models were
      effective in filtering and ranking the initially hypothesized annotations, and
      (ii) our learned models were significantly more accurate when external data
      sources were used during learning.

PMID- 15960831
TI  - A sentence sliding window approach to extract protein annotations from biomedical
      articles.
AB  - BACKGROUND: Within the emerging field of text mining and statistical natural
      language processing (NLP) applied to biomedical articles, a broad variety of
      techniques have been developed during the past years. Nevertheless, there is
      still a great ned of comparative assessment of the performance of the proposed
      methods and the development of common evaluation criteria. This issue was
      addressed by the Critical Assessment of Text Mining Methods in Molecular Biology
      (BioCreative) contest. The aim of this contest was to assess the performance of
      text mining systems applied to biomedical texts including tools which recognize
      named entities such as genes and proteins, and tools which automatically extract
      protein annotations. RESULTS: The "sentence sliding window" approach proposed
      here was found to efficiently extract text fragments from full text articles
      containing annotations on proteins, providing the highest number of correctly
      predicted annotations. Moreover, the number of correct extractions of individual
      entities (i.e. proteins and GO terms) involved in the relationships used for the
      annotations was significantly higher than the correct extractions of the complete
      annotations (protein-function relations). CONCLUSION: We explored the use of
      averaging sentence sliding windows for information extraction, especially in a
      context where conventional training data is unavailable. The combination of our
      approach with more refined statistical estimators and machine learning techniques
      might be a way to improve annotation extraction for future biomedical text mining
      applications.

PMID- 15960832
TI  - BioCreAtIvE task 1A: gene mention finding evaluation.
AB  - BACKGROUND: The biological research literature is a major repository of
      knowledge. As the amount of literature increases, it will get harder to find the
      information of interest on a particular topic. There has been an increasing
      amount of work on text mining this literature, but comparing this work is hard
      because of a lack of standards for making comparisons. To address this, we worked
      with colleagues at the Protein Design Group, CNB-CSIC, Madrid to develop
      BioCreAtIvE (Critical Assessment for Information Extraction in Biology), an open
      common evaluation of systems on a number of biological text mining tasks. We
      report here on task 1A, which deals with finding mentions of genes and related
      entities in text. "Finding mentions" is a basic task, which can be used as a
      building block for other text mining tasks. The task makes use of data and
      evaluation software provided by the (US) National Center for Biotechnology
      Information (NCBI). RESULTS: 15 teams took part in task 1A. A number of teams
      achieved scores over 80% F-measure (balanced precision and recall). The teams
      that tried to use their task 1A systems to help on other BioCreAtIvE tasks
      reported mixed results. CONCLUSION: The 80% plus F-measure results are good, but
      still somewhat lag the best scores achieved in some other domains such as
      newswire, due in part to the complexity and length of gene names, compared to
      person or organization names in newswire.

PMID- 15960833
TI  - Protein annotation as term categorization in the gene ontology using word
      proximity networks.
AB  - BACKGROUND: We participated in the BioCreAtIvE Task 2, which addressed the
      annotation of proteins into the Gene Ontology (GO) based on the text of a given
      document and the selection of evidence text from the document justifying that
      annotation. We approached the task utilizing several combinations of two distinct
      methods: an unsupervised algorithm for expanding words associated with GO nodes,
      and an annotation methodology which treats annotation as categorization of terms
      from a protein's document neighborhood into the GO. RESULTS: The evaluation
      results indicate that the method for expanding words associated with GO nodes is
      quite powerful; we were able to successfully select appropriate evidence text for
      a given annotation in 38% of Task 2.1 queries by building on this method. The
      term categorization methodology achieved a precision of 16% for annotation within
      the correct extended family in Task 2.2, though we show through subsequent
      analysis that this can be improved with a different parameter setting. Our
      architecture proved not to be very successful on the evidence text component of
      the task, in the configuration used to generate the submitted results.
      CONCLUSION: The initial results show promise for both of the methods we explored,
      and we are planning to integrate the methods more closely to achieve better
      results overall.

PMID- 15960834
TI  - Finding genomic ontology terms in text using evidence content.
AB  - BACKGROUND: The development of text mining systems that annotate biological
      entities with their properties using scientific literature is an important recent
      research topic. These systems need first to recognize the biological entities and
      properties in the text, and then decide which pairs represent valid annotations.
      METHODS: This document introduces a novel unsupervised method for recognizing
      biological properties in unstructured text, involving the evidence content of
      their names. RESULTS: This document shows the results obtained by the application
      of our method to BioCreative tasks 2.1 and 2.2, where it identified Gene Ontology
      annotations and their evidence in a set of articles. CONCLUSION: From the
      performance obtained in BioCreative, we concluded that an automatic annotation
      system can effectively use our method to identify biological properties in
      unstructured text.

PMID- 15960835
TI  - Mining protein function from text using term-based support vector machines.
AB  - BACKGROUND: Text mining has spurred huge interest in the domain of biology. The
      goal of the BioCreAtIvE exercise was to evaluate the performance of current text
      mining systems. We participated in Task 2, which addressed assigning Gene
      Ontology terms to human proteins and selecting relevant evidence from full-text
      documents. We approached it as a modified form of the document classification
      task. We used a supervised machine-learning approach (based on support vector
      machines) to assign protein function and select passages that support the
      assignments. As classification features, we used a protein's co-occurring terms
      that were automatically extracted from documents. RESULTS: The results evaluated
      by curators were modest, and quite variable for different problems: in many cases
      we have relatively good assignment of GO terms to proteins, but the selected
      supporting text was typically non-relevant (precision spanning from 3% to 50%).
      The method appears to work best when a substantial set of relevant documents is
      obtained, while it works poorly on single documents and/or short passages. The
      initial results suggest that our approach can also mine annotations from text
      even when an explicit statement relating a protein to a GO term is absent.
      CONCLUSION: A machine learning approach to mining protein function predictions
      from text can yield good performance only if sufficient training data is
      available, and significant amount of supporting data is used for prediction. The
      most promising results are for combined document retrieval and GO term
      assignment, which calls for the integration of methods developed in BioCreAtIvE
      Task 1 and Task 2.

PMID- 15960836
TI  - Data-poor categorization and passage retrieval for gene ontology annotation in
      Swiss-Prot.
AB  - BACKGROUND: In the context of the BioCreative competition, where training data
      were very sparse, we investigated two complementary tasks: 1) given a Swiss-Prot
      triplet, containing a protein, a GO (Gene Ontology) term and a relevant article,
      extraction of a short passage that justifies the GO category assignment; 2) given
      a Swiss-Prot pair, containing a protein and a relevant article, automatic
      assignment of a set of categories. METHODS: Sentence is the basic retrieval unit.
      Our classifier computes a distance between each sentence and the GO category
      provided with the Swiss-Prot entry. The Text Categorizer computes a distance
      between each GO term and the text of the article. Evaluations are reported both
      based on annotator judgements as established by the competition and based on mean
      average precision measures computed using a curated sample of Swiss-Prot.
      RESULTS: Our system achieved the best recall and precision combination both for
      passage retrieval and text categorization as evaluated by official evaluators.
      However, text categorization results were far below those in other data-poor text
      categorization experiments The top proposed term is relevant in less that 20% of
      cases, while categorization with other biomedical controlled vocabulary, such as
      the Medical Subject Headings, we achieved more than 90% precision. We also
      observe that the scoring methods used in our experiments, based on the retrieval
      status value of our engines, exhibits effective confidence estimation
      capabilities. CONCLUSION: From a comparative perspective, the combination of
      retrieval and natural language processing methods we designed, achieved very
      competitive performances. Largely data-independent, our systems were no less
      effective that data-intensive approaches. These results suggests that the overall
      strategy could benefit a large class of information extraction tasks, especially
      when training data are missing. However, from a user perspective, results were
      disappointing. Further investigations are needed to design applicable end-user
      text mining tools for biologists.

PMID- 15960837
TI  - GENETAG: a tagged corpus for gene/protein named entity recognition.
AB  - BACKGROUND: Named entity recognition (NER) is an important first step for text
      mining the biomedical literature. Evaluating the performance of biomedical NER
      systems is impossible without a standardized test corpus. The annotation of such
      a corpus for gene/protein name NER is a difficult process due to the complexity
      of gene/protein names. We describe the construction and annotation of GENETAG, a
      corpus of 20K MEDLINE sentences for gene/protein NER. 15K GENETAG sentences were
      used for the BioCreAtIvE Task 1A Competition. RESULTS: To ensure heterogeneity of
      the corpus, MEDLINE sentences were first scored for term similarity to documents
      with known gene names, and 10K high- and 10K low-scoring sentences were chosen at
      random. The original 20K sentences were run through a gene/protein name tagger,
      and the results were modified manually to reflect a wide definition of
      gene/protein names subject to a specificity constraint, a rule that required the
      tagged entities to refer to specific entities. Each sentence in GENETAG was
      annotated with acceptable alternatives to the gene/protein names it contained,
      allowing for partial matching with semantic constraints. Semantic constraints are
      rules requiring the tagged entity to contain its true meaning in the sentence
      context. Application of these constraints results in a more meaningful measure of
      the performance of an NER system than unrestricted partial matching. CONCLUSION:
      The annotation of GENETAG required intricate manual judgments by annotators which
      hindered tagging consistency. The data were pre-segmented into words, to provide
      indices supporting comparison of system responses to the "gold standard".
      However, character-based indices would have been more robust than word-based
      indices. GENETAG Train, Test and Round1 data and ancillary programs are freely
      available at ftp://ftp.ncbi.nlm.nih.gov/pub/tanabe/GENETAG.tar.gz. A newer
      version of GENETAG-05, will be released later this year.

PMID- 15960838
TI  - BioCreAtIvE task1A: entity identification with a stochastic tagger.
AB  - BACKGROUND: Our approach to Task 1A was inspired by Tanabe and Wilbur's ABGene
      system. Like Tanabe and Wilbur, we approached the problem as one of part-of
      speech tagging, adding a GENE tag to the standard tag set. Where their system
      uses the Brill tagger, we used TnT, the Trigrams 'n' Tags HMM-based part-of
      speech tagger. Based on careful error analysis, we implemented a set of post
      processing rules to correct both false positives and false negatives. We
      participated in both the open and the closed divisions; for the open division, we
      made use of data from NCBI. RESULTS: Our base system without post-processing
      achieved a precision and recall of 68.0% and 77.2%, respectively, giving an F
      measure of 72.3%. The full system with post-processing achieved a precision and
      recall of 80.3% and 80.5% giving an F-measure of 80.4%. We achieved a slight
      improvement (F-measure = 80.9%) by employing a dictionary-based post-processing
      step for the open division. We placed third in both the open and the closed
      division. CONCLUSION: Our results show that a part-of-speech tagger can be
      augmented with post-processing rules resulting in an entity identification system
      that competes well with other approaches.

PMID- 15960839
TI  - Exploring the boundaries: gene and protein identification in biomedical text.
AB  - BACKGROUND: Good automatic information extraction tools offer hope for automatic
      processing of the exploding biomedical literature, and successful named entity
      recognition is a key component for such tools. METHODS: We present a maximum
      entropy based system incorporating a diverse set of features for identifying gene
      and protein names in biomedical abstracts. RESULTS: This system was entered in
      the BioCreative comparative evaluation and achieved a precision of 0.83 and
      recall of 0.84 in the "open" evaluation and a precision of 0.78 and recall of
      0.85 in the "closed" evaluation. CONCLUSION: Central contributions are rich use
      of features derived from the training data at multiple levels of granularity, a
      focus on correctly identifying entity boundaries, and the innovative use of
      several external knowledge sources including full MEDLINE abstracts and web
      searches.

PMID- 15960840
TI  - Identifying gene and protein mentions in text using conditional random fields.
AB  - BACKGROUND: We present a model for tagging gene and protein mentions from text
      using the probabilistic sequence tagging framework of conditional random fields
      (CRFs). Conditional random fields model the probability P(t/o) of a tag sequence
      given an observation sequence directly, and have previously been employed
      successfully for other tagging tasks. The mechanics of CRFs and their
      relationship to maximum entropy are discussed in detail. RESULTS: We employ a
      diverse feature set containing standard orthographic features combined with
      expert features in the form of gene and biological term lexicons to achieve a
      precision of 86.4% and recall of 78.7%. An analysis of the contribution of the
      various features of the model is provided.

PMID- 15960841
TI  - Recognition of protein/gene names from text using an ensemble of classifiers.
AB  - This paper proposes an ensemble of classifiers for biomedical name recognition in
      which three classifiers, one Support Vector Machine and two discriminative Hidden
      Markov Models, are combined effectively using a simple majority voting strategy.
      In addition, we incorporate three post-processing modules, including an
      abbreviation resolution module, a protein/gene name refinement module and a
      simple dictionary matching module, into the system to further improve the
      performance. Evaluation shows that our system achieves the best performance from
      among 10 systems with a balanced F-measure of 82.58 on the closed evaluation of
      the BioCreative protein/gene name recognition task (Task 1A).

PMID- 15960842
TI  - Gene/protein name recognition based on support vector machine using dictionary as
      features.
AB  - BACKGROUND: Automated information extraction from biomedical literature is
      important because a vast amount of biomedical literature has been published.
      Recognition of the biomedical named entities is the first step in information
      extraction. We developed an automated recognition system based on the SVM
      algorithm and evaluated it in Task 1.A of BioCreAtIvE, a competition for
      automated gene/protein name recognition. RESULTS: In the work presented here, our
      recognition system uses the feature set of the word, the part-of-speech (POS),
      the orthography, the prefix, the suffix, and the preceding class. We call these
      features "internal resource features", i.e., features that can be found in the
      training data. Additionally, we consider the features of matching against
      dictionaries to be external resource features. We investigated and evaluated the
      effect of these features as well as the effect of tuning the parameters of the
      SVM algorithm. We found that the dictionary matching features contributed
      slightly to the improvement in the performance of the f-score. We attribute this
      to the possibility that the dictionary matching features might overlap with other
      features in the current multiple feature setting. CONCLUSION: During SVM
      learning, each feature alone had a marginally positive effect on system
      performance. This supports the fact that the SVM algorithm is robust on the high
      dimensionality of the feature vector space and means that feature selection is
      not required.

PMID- 15960843
TI  - Systematic feature evaluation for gene name recognition.
AB  - In task 1A of the BioCreAtIvE evaluation, systems had to be devised that
      recognize words and phrases forming gene or protein names in natural language
      sentences. We approach this problem by building a word classification system
      based on a sliding window approach with a Support Vector Machine, combined with a
      pattern-based post-processing for the recognition of phrases. The performance of
      such a system crucially depends on the type of features chosen for consideration
      by the classification method, such as pre- or postfixes, character n-grams,
      patterns of capitalization, or classification of preceding or following words. We
      present a systematic approach to evaluate the performance of different feature
      sets based on recursive feature elimination, RFE. Based on a systematic reduction
      of the number of features used by the system, we can quantify the impact of
      different feature sets on the results of the word classification problem. This
      helps us to identify descriptive features, to learn about the structure of the
      problem, and to design systems that are faster and easier to understand. We
      observe that the SVM is robust to redundant features. RFE improves the
      performance by 0.7%, compared to using the complete set of attributes. Moreover,
      a performance that is only 2.3% below this maximum can be obtained using fewer
      than 5% of the features.

PMID- 15960844
TI  - Cancer history and other personal factors affect quality of life in patients with
      hepatitis C.
AB  - BACKGROUND: Although patients with chronic hepatitis C (CHC) have been found to
      have reduced quality of life, little is known about how other characteristics
      affect their quality of life. The purpose of this study was to investigate the
      effect of other characteristics, including history of cancer, on quality of life
      in patients with CHC. METHODS: One hundred forty patients from clinics at three
      hospitals in New York City completed a detailed epidemiologic interview about
      demographic and lifestyle characteristics and the SF-36 measuring health-related
      quality of life. We compared results from our patients to normative data using t
      tests of differences between means. We used multivariate analyses to determine
      other personal and health-related factors associated with quality of life
      outcomes. RESULTS: Compared to normative data, these patients had reduced quality
      of life, particularly on physical functioning. The summary Physical Component
      Score (PCS) was 45.4 +/- 10.6 and the Mental Component Score (MCS) was 48.2 +/-
      11.1, vs norms of 50 +/- 10.0; p-values were < 0.0001 and < 0.05, respectively.
      In multivariate analyses, the PCS was significantly lower among those with cancer
      history, > or = 2 other chronic conditions, less education, low physical
      activity, and higher alanine aminotransferase (ALT) levels. Cancer was more
      important for men, while other chronic conditions were more important for women.
      On the MCS, history of depression, low physical activity, alcohol use, and female
      gender were independently associated with poorer scores. CONCLUSION: Several
      health and lifestyle factors independently influence quality of life in CHC
      patients. Different factors are important for men and women.

PMID- 15960845
TI  - Differential localization of HPV16 E6 splice products with E6-associated protein.
AB  - High-risk Human Papillomavirus (HPV) is the etiological agent associated with the
      majority of anogenital cancers. The primary HPV oncogenes, E6 and E7, undergo a
      complex splicing program resulting in protein products whose purpose is not fully
      understood. Previous mouse studies have confirmed the existence of a translated
      product corresponding to the E6*I splice product. In terms of function, the
      translated E6*I protein has been shown to bind to E6 protein and to E6 associated
      protein (E6AP). E6*I has an inhibitory effect on E6-mediated p53 degradation in
      E6 expressing cells. In order to analyze the relationship between E6*I and full
      length E6 in relation to localization, we created a series of green fluorescent
      protein (GFP) fusion products. The localization of these proteins with reference
      to E6AP in vivo remains unclear. Therefore, we investigated the cellular
      distribution of different forms of E6 with reference to E6AP. E6 and E6*I
      proteins, expressed from a wild type E6 gene cassette, were dispersed in the
      nucleus and the cytoplasm. Whereas, the E6 splice donor mutant (E6MT) was
      primarily localized to the nucleus. E6*I protein and E6AP were found to co
      localize mainly to the cytoplasm, whereas the co-localization of full-length E6
      protein and E6AP, if at all, was found mainly at the perinuclear region. These
      results suggest a functional relationship between the E6*I and full-length E6
      protein which correlates with their localization and likely is important in
      regulation of the E6-E6AP complex.

PMID- 15960846
TI  - Evidence for abundant transcription of non-coding regions in the Saccharomyces
      cerevisiae genome.
AB  - BACKGROUND: Recent studies in a growing number of organisms have yielded
      accumulating evidence that a significant portion of the non-coding region in the
      genome is transcribed. We address this issue in the yeast Saccharomyces
      cerevisiae. RESULTS: Taking into account the absence of a significantly large
      yeast EST database, we use microarray expression data collected for genomic
      regions erroneously believed to be coding to study the expression pattern of non
      coding regions in the Saccharomyces cerevisiae genome. We find that at least 164
      out of 589 (28%) such regions are expressed under specific biological conditions.
      In particular, looking at the probes that are located opposing other known genes
      at the same genomic locus, we find that 88 out of 341 (26%) of these genes
      support antisense transcription. The expression patterns of these antisense genes
      are positively correlated. We validate these results using RT-PCR on a sample of
      6 non-coding transcripts. CONCLUSION: 1. The yeast genome is transcribed on a
      scale larger than previously assumed. 2. Correlated transcription of antisense
      genes is abundant in the yeast genome. 3. Antisense genes in yeast are non
      coding.

PMID- 15960847
TI  - Tree measures and the number of segregating sites in time-structured population
      samples.
AB  - BACKGROUND: Time-structured genetic samples are a valuable source of information
      in population genetics because they provide several correlated observations of
      the underlying evolutionary processes. In this paper we study basic properties of
      the genetic variation in time-structured samples as reflected in the genealogies
      relating individuals and the number of segregating sites observed. Our emphasis
      is on "measurably evolving populations" i.e. populations from which it is
      possible to obtain time-structured samples that span a significant interval of
      evolutionary time. RESULTS: We use results from the coalescent process to derive
      properties of time-structured samples. In the first section we extend existing
      results to attain measures on coalescent trees relating time-structured samples.
      These include the expected time to a most recent common ancestor, the expected
      total branch length and the expected length of branches subtending only ancient
      individuals. The effect of different sampling schemes on the latter measure is
      studied. In the second section we study the special case where the full sample
      consists of a group of contemporary extant samples and a group of contemporary
      ancient samples. As regards this case, we present results and applications
      concerning the probability distribution of the number of segregating sites where
      a mutation is unique to the ancient individuals and the number of segregating
      sites where a mutation is shared between ancient and extant individuals.
      CONCLUSION: The methodology and results presented here is of use to the design
      and interpretation of ancient DNA experiments. Furthermore, the results may be
      useful in further development of statistical tests of e.g. population dynamics
      and selection, which include temporal information.

PMID- 15960848
TI  - The role of vocal individuality in conservation.
AB  - Identifying the individuals within a population can generate information on life
      history parameters, generate input data for conservation models, and highlight
      behavioural traits that may affect management decisions and error or bias within
      census methods. Individual animals can be discriminated by features of their
      vocalisations. This vocal individuality can be utilised as an alternative marking
      technique in situations where the marks are difficult to detect or animals are
      sensitive to disturbance. Vocal individuality can also be used in cases were the
      capture and handling of an animal is either logistically or ethically
      problematic. Many studies have suggested that vocal individuality can be used to
      count and monitor populations over time; however, few have explicitly tested the
      method in this role. In this review we discuss methods for extracting
      individuality information from vocalisations and techniques for using this to
      count and monitor populations over time. We present case studies in birds where
      vocal individuality has been applied to conservation and we discuss its role in
      mammals.

PMID- 15960849
TI  - The effect of illustrations on patient comprehension of medication instruction
      labels.
AB  - BACKGROUND: Labels with special instructions regarding how a prescription
      medication should be taken or its possible side effects are often applied to pill
      bottles. The goal of this study was to determine whether the addition of
      illustrations to these labels affects patient comprehension. METHODS: Study
      participants (N = 130) were enrolled by approaching patients at three family
      practice clinics in Toronto, Canada. Participants were asked to interpret two
      sets of medication instruction labels, the first with text only and the second
      with the same text accompanied by illustrations. Two investigators coded
      participants' responses as incorrect, partially correct, or completely correct.
      Health literacy levels of participants were measured using a validated
      instrument, the REALM test. RESULTS: All participants gave a completely correct
      interpretation for three out of five instruction labels, regardless of whether
      illustrations were present or not. For the two most complex labels, only 34-55%
      of interpretations of the text-only version were completely correct. The addition
      of illustrations was associated with improved performance in 5-7% of subjects and
      worsened performance in 7-9% of subjects. CONCLUSION: The commonly-used
      illustrations on the medication labels used in this study were of little or no
      use in improving patients' comprehension of the accompanying written
      instructions.

PMID- 15960850
TI  - Cell membrane array fabrication and assay technology.
AB  - BACKGROUND: Microarray technology has been used extensively over the past 10
      years for assessing gene expression, and has facilitated precise genetic
      profiling of everything from tumors to small molecule drugs. By contrast,
      arraying cell membranes in a manner which preserves their ability to mediate
      biochemical processes has been considerably more difficult. RESULTS: In this
      article, we describe a novel technology for generating cell membrane microarrays
      for performing high throughput biology. Our robotically-arrayed supported
      membranes are physiologically fluid, a critical property which differentiates
      this technology from other previous membrane systems and makes it useful for
      studying cellular processes on an industrialized scale. Membrane array elements
      consist of a solid substrate, above which resides a fluid supported lipid bilayer
      containing biologically-active molecules of interest. Incorporation of
      transmembrane proteins into the arrayed membranes enables the study of
      ligand/receptor binding, as well as interactions with live intact cells. The
      fluidity of these molecules in the planar lipid bilayer facilitates dimerization
      and other higher order interactions necessary for biological signaling events. In
      order to demonstrate the utility of our fluid membrane array technology to
      ligand/receptor studies, we investigated the multivalent binding of the cholera
      toxin B-subunit (CTB) to the membrane ganglioside GM1. We have also displayed a
      number of bona fide drug targets, including bacterial endotoxin (also referred to
      as lipopolysaccharide (LPS)) and membrane proteins important in T cell
      activation. CONCLUSION: We have demonstrated the applicability of our fluid cell
      membrane array technology to both academic research applications and industrial
      drug discovery. Our technology facilitates the study of ligand/receptor
      interactions and cell-cell signaling, providing rich qualitative and quantitative
      information.

PMID- 15960851
TI  - Signature proteins that are distinctive of alpha proteobacteria.
AB  - BACKGROUND: The alpha (alpha) proteobacteria, a very large and diverse group, are
      presently characterized solely on the basis of 16S rRNA trees, with no known
      molecular characteristic that is unique to this group. The genomes of three alpha
      proteobacteria, Rickettsia prowazekii (RP), Caulobacter crescentus (CC) and
      Bartonella quintana (BQ), were analyzed in order to search for proteins that are
      unique to this group. RESULTS: Blast analyses of protein sequences from the above
      genomes have led to the identification of 61 proteins which are distinctive
      characteristics of alpha-proteobacteria and are generally not found in any other
      bacteria. These alpha-proteobacterial signature proteins are generally of
      hypothetical functions and they can be classified as follows: (i) Six proteins
      (CC2102, CC3292, CC3319, CC1887, CC1725 and CC1365) which are uniquely present in
      most sequenced alpha-proteobacterial genomes; (ii) Ten proteins (CC1211, CC1886,
      CC2245, CC3470, CC0520, CC0365, CC0366, CC1977, CC3010 and CC0100) which are
      present in all alpha-proteobacteria except the Rickettsiales; (iii) Five proteins
      (CC2345, CC3115, CC3401, CC3467 and CC1021) not found in the intracellular
      bacteria belonging to the order Rickettsiales and the Bartonellaceae family; (iv)
      Four proteins (CC1652, CC2247, CC3295 and CC1035) that are absent from various
      Rickettsiales as well as Rhodobacterales; (v) Three proteins (RP104, RP105 and
      RP106) that are unique to the order Rickettsiales and four proteins (RP766,
      RP192, RP030 and RP187) which are specific for the Rickettsiaceae family; (vi)
      Six proteins (BQ00140, BQ00720, BQ03880, BQ12030, BQ07670 and BQ11900) which are
      specific to the order Rhizobiales; (vii) Four proteins (BQ01660, BQ02450, BQ03770
      and BQ13470) which are specific for the order Rhizobiales excluding the family
      Bradyrhizobiaceae; (viii) Nine proteins (BQ12190, BQ11460, BQ11450, BQ11430,
      BQ11380, BQ11160, BQ11120, BQ11100 and BQ11030 which are distinctive of the
      Bartonellaceae family;(ix) Six proteins (CC0189, CC0569, CC0331, CC0349, CC2323
      and CC2637) which show sporadic distribution in alpha-proteobacteria, (x) Four
      proteins (CC2585, CC0226, CC2790 and RP382) in which lateral gene transfers are
      indicated to have occurred between alpha-proteobacteria and a limited number of
      other bacteria. CONCLUSION: The identified proteins provide novel means for
      defining and identifying the alpha-proteobacteria and many of its subgroups in
      clear molecular terms and in understanding the evolution of this group of
      species. These signature proteins, together with the large number of alpha
      proteobacteria specific indels that have recently been identified
      http://www.bacterialphylogeny.com, provide evidence that all species from this
      diverse group share many unifying and distinctive characteristics. Functional
      studies on these proteins should prove very helpful in the identification of such
      characteristics.

PMID- 15960852
TI  - The DiGEM trial protocol--a randomised controlled trial to determine the effect
      on glycaemic control of different strategies of blood glucose self-monitoring in
      people with type 2 diabetes [ISRCTN47464659].
AB  - BACKGROUND: We do not yet know how to use blood glucose self-monitoring (BGSM)
      most effectively in the self-management of type 2 diabetes treated with oral
      medication. Training in monitoring may be most effective in improving glycaemic
      control and well being when results are linked to behavioural change.
      METHODS/DESIGN: DiGEM is a three arm randomised parallel group trial set in UK
      general practices. A total of 450 patients with type 2 diabetes managed with
      lifestyle or oral glucose lowering medication are included. The trial compares
      effectiveness of three strategies for monitoring glycaemic control over 12 months
      (1) a control group with three monthly HbA1c measurements; interpreted with nurse
      practitioner; (2) A self-testing of blood glucose group; interpreted with nurse-
      practitioner to inform adjustment of medication in addition to 1; (3) A self
      monitoring of blood glucose group with personal use of results to interpret
      results in relation to lifestyle changes in addition to 1 and 2. The trial has an
      80% power at a 5% level of significance to detect a difference in change in the
      primary outcome, HbA1c of 0.5% between groups, allowing for an attrition rate of
      10%. Secondary outcome measures include health service costs, well-being, and the
      intervention effect in sub-groups defined by duration of diabetes, current
      management, health status at baseline and co-morbidity. A mediation analysis will
      explore the extent to which changes in beliefs about self-management of diabetes
      between experimental groups leads to changes in outcomes in accordance with the
      Common Sense Model of illness. The study is open and has recruited more than half
      the target sample. The trial is expected to report in 2007. DISCUSSION: The DiGEM
      intervention and trial design address weaknesses of previous research by use of a
      sample size with power to detect a clinically significant change in HbA1c,
      recruitment from a well-characterised primary care population, definition of
      feasible monitoring and behaviour change strategies based on psychological theory
      and evidence, and measures along the hypothesised causal path from cognitions to
      behaviours and disease and well being related outcomes. The trial will provide
      evidence to support, focus or discourage use of specific BGSM strategies.

PMID- 15960853
TI  - Polymorphisms within the canine MLPH gene are associated with dilute coat color
      in dogs.
AB  - BACKGROUND: Pinschers and other dogs with coat color dilution show a
      characteristic pigmentation phenotype. The fur colors are a lighter shade, e.g.
      silvery grey (blue) instead of black and a sandy color (Isabella fawn) instead of
      red or brown. In some dogs the coat color dilution is sometimes accompanied by
      hair loss and recurrent skin inflammation, the so called color dilution alopecia
      (CDA) or black hair follicular dysplasia (BHFD). In humans and mice a comparable
      pigmentation phenotype without any documented hair loss is caused by mutations
      within the melanophilin gene (MLPH). RESULTS: We sequenced the canine MLPH gene
      and performed a mutation analysis of the MLPH exons in 6 Doberman Pinschers and 5
      German Pinschers. A total of 48 sequence variations was identified within and
      between the breeds. Three families of dogs showed co-segregation for at least one
      polymorphism in an MLPH exon and the dilute phenotype. No single polymorphism was
      identified in the coding sequences or at splice sites that is likely to be
      causative for the dilute phenotype of all dogs examined. In 18 German Pinschers a
      mutation in exon 7 (R199H) was consistently associated with the dilute phenotype.
      However, as this mutation was present in homozygous state in four dogs of other
      breeds with wildtype pigmentation, it seems unlikely that this mutation is truly
      causative for coat color dilution. In Doberman Pinschers as well as in Large
      Munsterlanders with BHFD, a set of single nucleotide polymorphisms (SNPs) around
      exon 2 was identified that show a highly significant association to the dilute
      phenotype. CONCLUSION: This study provides evidence that coat color dilution is
      caused by one or more mutations within or near the MLPH gene in several dog
      breeds. The data on polymorphisms that are strongly associated with the dilute
      phenotype will allow the genetic testing of Pinschers to facilitate the breeding
      of dogs with defined coat colors and to select against Large Munsterlanders
      carrying BHFD.

PMID- 15960854
TI  - AnovArray: a set of SAS macros for the analysis of variance of gene expression
      data.
AB  - BACKGROUND: Analysis of variance is a powerful approach to identify
      differentially expressed genes in a complex experimental design for microarray
      and macroarray data. The advantage of the anova model is the possibility to
      evaluate multiple sources of variation in an experiment. RESULTS: AnovArray is a
      package implementing ANOVA for gene expression data using SAS statistical
      software. The originality of the package is 1) to quantify the different sources
      of variation on all genes together, 2) to provide a quality control of the model,
      3) to propose two models for a gene's variance estimation and to perform a
      correction for multiple comparisons. CONCLUSION: AnovArray is freely available at
      http://www-mig.jouy.inra.fr/stat/AnovArray and requires only SAS statistical
      software.

PMID- 15960855
TI  - Manuscript Architect: a Web application for scientific writing in virtual
      interdisciplinary groups.
AB  - BACKGROUND: Although scientific writing plays a central role in the communication
      of clinical research findings and consumes a significant amount of time from
      clinical researchers, few Web applications have been designed to systematically
      improve the writing process. This application had as its main objective the
      separation of the multiple tasks associated with scientific writing into smaller
      components. It was also aimed at providing a mechanism where sections of the
      manuscript (text blocks) could be assigned to different specialists. Manuscript
      Architect was built using Java language in conjunction with the classic lifecycle
      development method. The interface was designed for simplicity and economy of
      movements. Manuscripts are divided into multiple text blocks that can be assigned
      to different co-authors by the first author. Each text block contains notes to
      guide co-authors regarding the central focus of each text block, previous
      examples, and an additional field for translation when the initial text is
      written in a language different from the one used by the target journal.
      Usability was evaluated using formal usability tests and field observations.
      RESULTS: The application presented excellent usability and integration with the
      regular writing habits of experienced researchers. Workshops were developed to
      train novice researchers, presenting an accelerated learning curve. The
      application has been used in over 20 different scientific articles and grant
      proposals. CONCLUSION: The current version of Manuscript Architect has proven to
      be very useful in the writing of multiple scientific texts, suggesting that
      virtual writing by interdisciplinary groups is an effective manner of scientific
      writing when interdisciplinary work is required.

PMID- 15960856
TI  - The incidence of varicella and herpes zoster in Massachusetts as measured by the
      Behavioral Risk Factor Surveillance System (BRFSS) during a period of increasing
      varicella vaccine coverage, 1998-2003.
AB  - BACKGROUND: The authors sought to monitor the impact of widespread varicella
      vaccination on the epidemiology of varicella and herpes zoster. While varicella
      incidence would be expected to decrease, mathematical models predict an initial
      increase in herpes zoster incidence if re-exposure to varicella protects against
      reactivation of the varicella zoster virus. METHODS: In 1998-2003, as varicella
      vaccine uptake increased, incidence of varicella and herpes zoster in
      Massachusetts was monitored using the random-digit-dial Behavioral Risk Factor
      Surveillance System. RESULTS: Between 1998 and 2003, varicella incidence declined
      from 16.5/1,000 to 3.5/1,000 (79%) overall with > or = 66% decreases for all age
      groups except adults (27% decrease). Age-standardized estimates of overall herpes
      zoster occurrence increased from 2.77/1,000 to 5.25/1,000 (90%) in the period
      1999-2003, and the trend in both crude and adjusted rates was highly significant
      (p < 0.001). Annual age-specific rates were somewhat unstable, but all increased,
      and the trend was significant for the 25-44 year and 65+ year age groups.
      CONCLUSION: As varicella vaccine coverage in children increased, the incidence of
      varicella decreased and the occurrence of herpes zoster increased. If the
      observed increase in herpes zoster incidence is real, widespread vaccination of
      children is only one of several possible explanations. Further studies are needed
      to understand secular trends in herpes zoster before and after use of varicella
      vaccine in the United States and other countries.

PMID- 15960857
TI  - AutoFACT: an automatic functional annotation and classification tool.
AB  - BACKGROUND: Assignment of function to new molecular sequence data is an essential
      step in genomics projects. The usual process involves similarity searches of a
      given sequence against one or more databases, an arduous process for large
      datasets. RESULTS: We present AutoFACT, a fully automated and customizable
      annotation tool that assigns biologically informative functions to a sequence.
      Key features of this tool are that it (1) analyzes nucleotide and protein
      sequence data; (2) determines the most informative functional description by
      combining multiple BLAST reports from several user-selected databases; (3)
      assigns putative metabolic pathways, functional classes, enzyme classes,
      GeneOntology terms and locus names; and (4) generates output in HTML, text and
      GFF formats for the user's convenience. We have compared AutoFACT to four well
      established annotation pipelines. The error rate of functional annotation is
      estimated to be only between 1-2%. Comparison of AutoFACT to the traditional top
      BLAST-hit annotation method shows that our procedure increases the number of
      functionally informative annotations by approximately 50%. CONCLUSION: AutoFACT
      will serve as a useful annotation tool for smaller sequencing groups lacking
      dedicated bioinformatics staff. It is implemented in PERL and runs on LINUX/UNIX
      platforms. AutoFACT is available at
      http://megasun.bch.umontreal.ca/Software/AutoFACT.htm.

PMID- 15960858
TI  - Genetics of human obesity.
AB  - The rapid development of new concepts and tools has led to a change in the way in
      which researchers carry out nutrition-related research. Obesity is determined by
      the interaction between predisposing genetic and environmental aspects, but at
      present the gene-gene and gene-environment interactions contributing to the
      development of this complex disease cannot be analysed in detail. The purpose of
      the present paper is to provide some examples of the knowledge that is available
      in the field of obesity genetics, and also the new strategies being developed
      that are aimed at studying the relative contribution of numerous genes to obesity
      and their responses to environmental changes. In the rare cases of monogenic
      obesities in which a major gene is the cause the molecular approach has proved
      extremely powerful in the identification of the genes responsible and in defining
      new syndromes. However, in the common forms of obesity (polygenic obesity) most
      studies have analysed genotype-phenotype associations without sometimes taking
      into account the influence of environmental factors (diet, sedentary lifestyle).
      Among the aspects limiting this integrated approach to obesity are the difficulty
      of having large enough samples and the expansion of biocomputing tools developed
      for accessing the question of multiple interactions with no a priori hypotheses.
      This picture is rapidly changing. Large databases of clinical data and DNA and
      biological sample banks with more precise environmental information and patient
      phenotypes are being compiled. The capacity for studying multiple genes
      simultaneously at the DNA or RNA levels is also possible. Finally, the tremendous
      progress in biocomputing will allow the integration of these different types of
      data (relating to environment, phenotype, genotype, gene expression) and will
      improve the ability to deal with this complex disease.

PMID- 15960859
TI  - Fetal origins of insulin resistance and obesity.
AB  - A number of epidemiological studies worldwide have demonstrated a relationship
      between poor early growth and an increased susceptibility to insulin resistance,
      visceral obesity, type 2 diabetes and other features of the metabolic syndrome in
      adulthood. However, the mechanistic basis of this relationship and the relative
      roles of genes and the environment remain a subject of debate. The 'thrifty
      phenotype' hypothesis proposes that poor fetal nutrition leads to programming of
      metabolism and an adult phenotype that is adapted to poor but not plentiful
      nutrition. The maternal reduced-protein rat model has been used to examine the
      importance of the maternal environment in determining susceptibility to adult
      disease. Pregnant and lactating rat dams are fed a diet containing 80 g
      protein/kg as compared with 200 g protein/kg, which leads to growth restriction
      in utero. Offspring of low-protein dams have increased susceptibility to
      diabetes, insulin resistance and hypertension when fed a palatable high-fat diet
      that promotes obesity. Administration of leptin during pregnancy and lactation to
      these protein-restricted dams produces offspring that have increased metabolic
      rate and do not become obese or insulin resistant when fed on a high-fat diet.
      Increased glucocorticoid exposure, particularly during late gestation, has been
      linked with insulin resistance in adulthood. High levels of fetal glucocorticoids
      may result from a decreased activity of placental 11beta-hydroxysteroid
      dehydrogenase (11beta-HSD) type 2, which normally protects the fetus from high
      maternal glucocorticoid levels. Leptin administration to protein-restricted dams
      inhibits the suppression of 11beta-HSD-2 and may be one mechanism by which the
      metabolic syndrome is prevented.

PMID- 15960860
TI  - Insights from the developing world: thrifty genotypes and thrifty phenotypes.
AB  - Few researchers would dispute that the pandemic of obesity is caused by a
      profound mismatch between humanity's present environmental circumstances and
      those that have moulded evolutionary selection. This concept was first
      articulated when gestational diabetes was described as being the result of a
      'thrifty genotype rendered detrimental by progress'. More recently, this
      hypothesis has been extended to the concept of a 'thrifty phenotype' to describe
      the metabolic adaptations adopted as a survival strategy by a malnourished fetus;
      changes that may also be inappropriate to deal with a later life of affluence.
      Both the thrifty genotype and the thrifty phenotype hypotheses would predict that
      populations in some areas of the developing world would be at greater risk of
      obesity and its co-morbidities; a proposition to be explored in the present
      paper. To date thrifty genes remain little more than a nebulous concept
      propagated by the intuitive logic that man has been selected to survive episodic
      famine and seasonal hungry periods. Under such conditions those individuals who
      could lay down extra energy stores and use them most efficiently would have a
      survival advantage. The search for candidate thrifty genes needs to cover every
      aspect of human energy balance from food-seeking behaviour to the coupling
      efficiency of oxidative phosphorylation. The present paper will describe examples
      of attempts to find thrifty genes in three selected candidate areas: maternally
      transmitted mitochondrial genes; the uncoupling proteins; apoE4, whose
      geographical distribution has been linked to a possible thrifty role in
      lipoprotein and cholesterol metabolism.

PMID- 15960861
TI  - Secretory factors from human adipose tissue and their functional role.
AB  - Obesity is characterized by an expanded adipose tissue mass. Recent data suggest
      that adipose tissue is a multi-functional organ rather than simply a passive
      storage site for excess energy. It has been clearly demonstrated that human
      adipose tissue produces a variety of secretory factors that exert multiple
      effects at both the local and the systemic level. To date, >100 products,
      covering a broad range of protein families as well as many fatty acids and
      prostaglandins, have been reported to be secreted by adipose tissue. The source
      of these secreted factors is not only mature fat cells but also poorly-identified
      cells present in the stromal-vascular fraction including macrophages. Secreted
      factors of particular interest include many cytokines or chemokines, such as TNF
      alpha, IL-6, IL-8, as well as plasminogen activator inhibitor-1, angiotensin-II,
      leptin, and adiponectin. In the obese state the expression and secretion of these
      factors is disturbed. With the exception of adiponectin, most circulating factors
      are elevated. From this perspective, obesity can be described as a pro
      inflammatory condition. In addition, regional differences in adipose expression
      of many of these factors have been found. There is now growing evidence that many
      secretory factors play an important role in the pathophysiology of the metabolic
      and cardiovascular complications of obesity. The question arising from these
      observations is how the secretory pattern of adipose tissue can be modified by
      dietary and pharmacological measures to reduce the health risks of obesity.

PMID- 15960862
TI  - The effects of conjugated linoleic acid on human health-related outcomes.
AB  - Conjugated linoleic acid (CLA) is a collective term for a mixture of positional
      and geometric isomers of conjugated dienoic derivatives of linoleic acid. CLA has
      received considerable attention as a result of animal experiments that report
      anti-carcinogenic, anti-atherogenic and anti-diabetic properties, and modulation
      of body composition and immune function. Several studies of CLA supplementation
      in human subjects have now been published, but in contrast to animal studies
      there has been marked variation between reports on the health-related outcomes.
      The consensus from seventeen published studies in human subjects is that CLA does
      not affect body weight or body composition. Some detrimental effects of the trans
      10,cis-12 CLA isomer have also been reported in terms of altered blood lipid
      composition and impaired insulin sensitivity. Finally, CLA has only limited
      effects on immune functions in man. However, there have been reports of some
      interesting isomer-specific effects of CLA on the blood lipid profile, but not on
      immune function. These isomer-specific effects need further investigation. Until
      more is known, CLA supplementation in man should be considered with caution.

PMID- 15960863
TI  - Bone turnover and nutritional status in Crohn's disease: relationship to
      circulating mononuclear cell function and response to fish oil and antioxidants.
AB  - Crohn's disease is associated with osteoporosis, malnutrition and altered
      function of peripheral blood mononuclear cells (PBMC). The responses of
      circulating immune cells and extra-intestinal manifestations to increased
      inflammatory activity and to modulation by dietary supplementation are uncertain.
      The relationships between disease status, bone turnover and body mass and
      composition, PBMC function and fatty acid availability have been investigated in
      patients with Crohn's disease. The availability of n-3 and n-6 PUFA is altered in
      adult patients and interferon (IFN)-gamma production by PBMC is lower. Increased
      inflammatory activity is associated with increased bone resorption in adult
      patients and decreased body mass in paediatric patients. In healthy male subjects
      there is a proportionate relationship between supplementary intake of EPA and DHA
      (0.3-2.0 g as fish oil/d) in combination with antioxidants (vitamins A, C and E
      and Se) and incorporation into plasma phospholipids and PBMC, and a non-linear
      relationship with PBMC synthesis of TNF-alpha, IL-6 and prostaglandin E2
      (decrease) and IFN-gamma (increase). In adults with Crohn's disease high-dose
      fish oil (2.7 g EPA+DHA/d) in combination with antioxidants (vitamins A, C and E
      and Se) increases the EPA and DHA content of PBMC and decreases the production of
      IFN-gamma by PBMC, but is not associated with effects on bone turnover or
      nutritional status.

PMID- 15960864
TI  - Vitamin D status and its relationship with parathyroid hormone and bone mineral
      status in older adolescents.
AB  - Osteoporosis is an important contributor to the global burden of disease, and in
      the UK alone results in one in three women and one in twelve men aged >50 years
      experiencing a fragility fracture. Optimising peak bone mass in early adulthood
      is thought to reduce osteoporosis risk by offsetting bone losses in later life.
      Ensuring sufficient vitamin D status (measured as 25-hydroxyvitamin D (25OHD) in
      plasma), among other factors, is believed to facilitate the achievement of
      optimum peak bone mass. Lower 25OHD is associated with a higher plasma
      concentration of parathyroid hormone (PTH). As PTH is associated with increased
      bone turnover and bone loss, maintenance of sufficient 25OHD is thought to have a
      protective effect on bone health. However, there is a lack of consensus
      internationally on what constitutes an optimum 25OHD concentration, and values
      between 30 and 80 nmol/l have been suggested. These values have been based on
      findings from various studies in adults in which PTH has been observed to plateau
      at a 25OHD concentration of >30 nmol/l; however, not all studies have found such
      a plateau. Although studies in younger adolescents (14-16 years) have shown an
      inverse relationship between PTH and 25OHD, the concentration of 25OHD required
      for achievement of optimum peak bone mass is unknown. The present review examines
      the evidence defining vitamin D insufficiency thresholds, and the relevance of
      such thresholds to adolescent bone health.

PMID- 15960865
TI  - Influence of triacylglycerol structure of stearic acid-rich fats on postprandial
      lipaemia.
AB  - Exaggerated postprandial lipaemia may increase the risk of CHD by contributing to
      both thrombotic and atherogenic processes. Previous research has focused on the
      quantity and composition of dietary fat, whereas the effect of triacylglycerol
      (TAG) structure on postprandial lipaemia and clotting factor VII activity has
      received little attention. TAG with similar fatty acid composition may have
      different biochemical and physical properties that are dependent on their TAG
      structure, and these differences may affect lipid metabolism. Recent findings
      suggest that differences in the physical properties of stearic acid-rich fats are
      associated with differences in postprandial lipaemia, and may play an important
      role in determining their rates of digestion and absorption.

PMID- 15960866
TI  - Peptide YY, appetite and food intake.
AB  - Obesity is taking on pandemic proportions. The laws of thermodynamics, however,
      remain unchanged, as energy will be stored if less energy is expended than
      consumed; the storage is usually in the form of adipose tissue. Several neural,
      humeral and psychological factors control the complex process known as appetite.
      Recently, a close evolutionary relationship between the gut and brain has become
      apparent. The gut hormones regulate important gastrointestinal functions such as
      motility, secretion, absorption, provide feedback to the central nervous system
      on availability of nutrients and may play a part in regulating food intake.
      Peptide YY (PYY) is a thirty-six amino acid peptide related to neuropeptide Y
      (NPY) and is co-secreted with glucagon-like peptide 1. Produced by the intestinal
      L-cells, the highest tissue concentrations of PYY are found in distal segments of
      the gastrointestinal tract, although it is present throughout the gut. Following
      food intake PYY is released into the circulation. PYY concentrations are
      proportional to meal energy content and peak plasma levels appear postprandially
      after 1 h. PYY3-36 is a major form of PYY in both the gut mucosal endocrine cells
      and the circulation. Peripheral administration of PYY3-36 inhibits food intake
      for several hours in both rodents and man. The binding of PYY3-36 to the Y2
      receptor leads to an inhibition of the NPY neurones and a possible reciprocal
      stimulation of the pro-opiomelanocortin neurones. Thus, PYY3-36 appears to
      control food intake by providing a powerful feedback on the hypothalamic
      circuits. The effect on food intake has been demonstrated at physiological
      concentrations and, therefore, PYY3-36 may be important in the everyday
      regulation of food intake.

PMID- 15960867
TI  - Dietary strategies for the prevention of obesity.
AB  - The rising tide of obesity has led to a resurgence of interest in dietary
      strategies to prevent excess weight gain. Data from controlled intervention
      studies is sparse, but nonetheless evidence from other diverse sources has
      identified a number of specific dietary factors and aspects of eating behaviour
      that either promote or protect against obesity. The present paper reviews the
      evidence in relation to energy density, the macronutrient composition of the
      diet, including the nature of carbohydrate foods and sugar-rich drinks, portion
      size and snacking habits. It concludes that there is now sufficient evidence to
      develop clear dietary guidelines to prevent weight gain that are largely
      consistent with those for the prevention of CVD and cancer. However, coordinated
      action across multiple stakeholders is also required if these guidelines are to
      be translated into sustained changes in eating habits.

PMID- 15960868
TI  - Physical activity and obesity prevention: a review of the current evidence.
AB  - Ecological data on temporal trends suggest that the rising prevalence of obesity
      is, at least in part, attributable to declining population energy expenditure.
      However, population-level data on trends in physical activity are scarce. In
      longitudinal cohort studies individuals who report higher levels of leisure-time
      physical activity tend to be less likely to gain weight, but studies vary in
      their conclusions because of issues of confounding, reverse causality and
      measurement error. The majority of studies suggest that low levels of activity
      are only weakly associated with future weight gain. Questions about dose-response
      can only be properly addressed by studies including objective measures of
      activity with known measurement error. The observational studies leave
      uncertainties about the direction of causality, as individuals who are overweight
      are less likely to stay active. Adjustment for confounding can diminish the
      impact of known confounders, but only randomisation can deal with issues of
      unmeasured confounding. Although there are a large number of clinical trials on
      the treatment of individuals with obesity or the prevention of weight regain
      among weight losers, the updated review of trials to prevent weight gain de novo
      only reveals six trials published since 2000 in adults and eleven in children.
      Not only are these trials relatively few in number but, for various
      methodological reasons, they are uncertain in their conclusions about whether
      increasing activity will be effective in preventing obesity. Whilst efforts
      should continue to enhance the evidence base it is wise, in the meantime, to
      stick to the consensus public health advice of advocating 45-60 min moderate
      intensity activity daily to prevent obesity.

PMID- 15960869
TI  - School- and family-based interventions to prevent overweight in children.
AB  - There have been only a few controlled studies on the prevention of overweight and
      obesity in children and adolescents. These studies differ in relation to
      strategy, setting, duration, focus, variables of outcome and statistical power,
      and therefore do not allow general conclusions to be made about the value of
      preventive measures. All school-based interventions aimed at the prevention of
      overweight and obesity show some improvement of health knowledge and health
      related behaviours. Short-term effects on nutritional state seem to be more
      pronounced in girls than in boys. School-based interventions can reduce the
      incidence of overweight. There is evidence that families of intermediate and high
      socio-economic status as well as intact families benefit more from treatment than
      families sharing other characteristics. Selected prevention in obese children is
      most successful when children are treated together with their parents. However,
      there are social barriers limiting the success of family-based interventions.
      Although some positive effects have been reported, simple interventions in a
      single area (e.g. a school health education programme) are unlikely to work on
      their own. The development of effective preventive interventions probably
      requires strategies that affect multiple settings simultaneously. At present
      there is no concerted action, rather many strategies in health promotion that are
      followed in isolation. Faced with the epidemic of overweight there is a need for
      national campaigns and action plans on childhood overweight and obesity. It is
      tempting to speculate that this strategy will also increase the value of isolated
      approaches (e.g. in schools and families).

PMID- 15960870
TI  - Obesity prevention: necessary and possible. A structured approach for effective
      planning.
AB  - Obesity is a serious public health problem that has important social, economic
      and health consequences. The prevalence of obesity is rising rapidly throughout
      the world in both rich and poor countries, and it affects all sections of
      society. There are several important reasons for addressing the prevention of
      obesity, rather than its treatment or management. The prevention of weight gain
      (or the reversal of small gains) and the maintenance of a healthy weight are
      likely to be easier, less expensive and potentially more effective than the
      treatment of obesity after it has fully developed. A structured planning
      framework for the identification of potential interventions for the promotion of
      healthy weight and the prevention of weight gain is clearly required. However,
      detailed reviews of the scientific literature have revealed that the body of
      research is too small to provide firm guidance on consistently-effective
      interventions for adults or children. Ultimately, a broader approach to evidence
      of effectiveness needs to be adopted. The present paper proposes a structured
      planning approach that utilises the portfolio model and allows the selection of
      interventions to be based on the best available evidence, while not excluding
      untried but promising strategies.

PMID- 15960871
TI  - The management of short-term intestinal failure in obese patients.
AB  - The prevalence of obesity in the general population is high and it is inevitable
      that artificial feeding will be needed from time to time in the obese patient,
      particularly in the critical care setting. Against a background of generous
      endogenous stores of energy as adipose tissue and the ability of obese
      individuals to survive starvation longer than non-obese individuals, emphasis is
      placed on preserving lean body mass and optimizing physiological function.
      Insulin resistance is typical of the obese individual and is exacerbated by
      stress; overfeeding is dangerous, particularly if it results in hyperglycaemia.
      Refeeding syndrome also has to be avoided. Weight may be difficult to measure and
      lean body mass difficult to assess. Calculation of energy requirements is
      therefore problematic in practice in the obese individual and there is
      substantial evidence from controlled clinical trials of the safety of feeding at
      or below resting energy expenditure. If this approach is taken it is wise to
      provide a more generous than normal protein intake and to beware of patients with
      a very high baseline urinary N excretion.

PMID- 15960872
TI  - Winter survival of larvae and pupae of the blowfly, Lucilia sericata (Diptera:
      Calliphoridae).
AB  - The mortality of larvae and pupae of the blowfly Lucilia sericata (Meigen) were
      examined during winter and spring, for two or three years. In soil cores in the
      field, 70-95% of the larvae died overwinter. Larvae congregated in the top 10 cm
      of the soil core and did not move extensively throughout the column during the
      winter. Larvae and pupae at greater depth were less likely to pupariate and
      emerge successfully than larvae closer to the surface. Under semi-natural
      conditions, where pupae were placed outside in sawdust filled tubes, in the
      absence of the usual biotic mortality factors, the mortality of larvae was
      considerably lower and was also unaffected by low winter temperatures. Hence, low
      temperatures did not appear to be the primary cause of high overwintering
      mortality in the field which, it is suggested, is more likely to be the result of
      the action of biotic mortality factors, such as entomopathogenic nematodes and
      fungi.

PMID- 15960873
TI  - Genetic diversity of woolly apple aphid Eriosoma lanigerum (Hemiptera: Aphididae)
      populations in the Western Cape, South Africa.
AB  - The woolly apple aphid Eriosoma lanigerum (Hausmann) is one of the most damaging
      apple pests in South Africa. Information on its genetic diversity is lacking and
      this study, in which the genetic structure of parthenogenetic E. lanigerum
      populations was characterized in the Western Cape Province of South Africa,
      represents the first local study of its kind. A total of 192 individuals from
      four different regions were collected and analysed using amplified fragment
      length polymorphism (AFLP). Using five selective AFLP primer pairs, 250 fragments
      were scored for analysis. Results indicated that a low level of genetic variation
      was apparent in E. lanigerum populations in the Western Cape (H = 0.0192).
      Furthermore, populations collected from geographically distant regions were very
      closely related, which can partly be explained by the fact that agricultural
      practices were responsible for dissemination of populations from a common
      ancestor to geographically distant areas. The low level of variation found
      indicated that the possibility of controlling E. lanigerum in the Western Cape
      using host plant resistance is favourable. This is the first report of AFLP being
      used to characterize the genetic structure of an aphid species. Results indicate
      that this marker may be useful for analysis of other aphid species.

PMID- 15960874
TI  - Bemisia argentifolii is a race of B. tabaci (Hemiptera: Aleyrodidae): the
      molecular genetic differentiation of B. tabaci populations around the world.
AB  - The phylogenetic relationships between genotypes of Bemisia tabaci were compared
      using ITS1 and CO1 nucleotide sequences. Phylogenetic and minimum spanning
      network analyses identified six major races, Asia, Bali, Australia, sub-Saharan
      Africa, Mediterranean/Asia Minor/Africa and New World as well as a large
      collection of genotypes from the Asia region with no strong association with any
      of the races. The term race is based on its usage in Mallet (2001). Mating
      incompatibility occurs between some races. There is insufficient data to raise
      races to species status, but the data supports the recognition of the six races
      and an unresolved core of ungrouped genotypes under the single Bemisia tabaci
      (Gennadius) species name. To clarify the identity of the race to which the B.
      tabaci under investigation is known, the following nomenclature is suggested, B.
      tabaci (Asia), B. tabaci (Bali), B. tabaci (Australia) B. tabaci (sub-Saharan
      Africa), B. tabaci (Mediterranean/Asia Minor/Africa) and B. tabaci (New World).
      Further, there is insufficient molecular or biological data to support the
      separation of B. tabaci and B. argentifolii Bellows & Perring and its use should
      be discontinued.

PMID- 15960875
TI  - Ticks associated with wild mammals in Ghana.
AB  - The host ranges of a collection of 21 tick species found on wild mammals in the
      savanna, forests and coastal zone of Ghana suggested that most species were
      adapted to feeding mainly on host species within a single mammalian order, i.e.
      on artiodactyls (bovids/suids), carnivores, rodents or pholidotes (pangolins).
      Only a few species were dispersed evenly across a range of orders. Seven out of
      ten of the most common ticks on forest mammals were significantly associated with
      a particular host species or a group of closely related host species, which could
      be viewed as their major host or hosts, but they were also recorded much less
      frequently on a wide range of host species. Two other species were confined to
      their major hosts. Only one species appeared to be widely dispersed on forest
      mammals and to lack a particular major host. The majority of tick species
      therefore occurred on hosts with very distinctive biological, behavioural and
      ecological characteristics. The study provided no evidence to support the view
      that host specificity is an artefact of sampling. Finding that the tick species
      on Ghanaian wild mammals occurred on particular hosts, as well as in distinct
      habitats, indicated that tick-host associations are important for tick survival
      and confirmed the importance of climate and vegetation in tick distribution.

PMID- 15960876
TI  - Artificial larviposition sites for field collections of the puparia of tsetse
      flies Glossina pallidipes and G. m. morsitans (Diptera: Glossinidae).
AB  - Tsetse flies Glossina pallidipes Austen and G. morsitans morsitans Westwood
      deposit their larvae in warthog burrows, in August-November, at Rekomitjie
      Research Station, Zambezi Valley, Zimbabwe. Artificial burrows, made from 200-l
      steel drums, were used to sample these flies and to collect their puparia. Sand
      filled plastic trays in the burrows served as a substrate for larval deposition.
      The sand was covered with c. 2 cm of leaf litter after it was shown that only 3%
      of larvae were deposited on bare sand if both substrates were available. Other
      burrow modifications - artificially shading the burrow entrance, increasing the
      relative humidity inside the burrow, or reducing the size of the burrow entrance 
      significantly decreased deposition rates. The use of burrows in the hot season
      results in a reduction in the temperature experienced by the puparium towards an
      assumed optimum level of 26 degrees C. Artificial burrows maintained a mean
      temperature of 28.5 degrees C during October-November 1998, c. 2.5 degrees C
      cooler than ambient; earlier work has shown that natural burrows can be c. 5
      degrees C cooler than ambient at these times. This may explain why natural
      burrows in full sunlight were used for larviposition, whereas artificial burrows
      were used only when they were in deep shade, and why significantly higher
      proportions of G. pallidipes were found in natural (66%) than in artificial
      burrows (34%). Better-insulated artificial burrows might produce more puparia
      with higher proportions of G. pallidipes. Burrows become waterlogged during the
      rains and may be too cool for optimum puparial development during the rest of the
      year. The percentages of G. m. morsitans in catches of females from artificial
      burrows, refuges and odour-baited traps were 34, 26 and < 10% respectively. Traps
      are biased in favour of G. pallidipes; artificial burrows may show a bias in
      favour of G. m. morsitans that is a function of temperature. Artificial warthog
      burrows provide a convenient way of studying the puparial stage in tsetse and for
      the first time facilitate the capture of females as they deposit their larvae.

PMID- 15960877
TI  - Host finding by Uscana lariophaga (Hymenoptera: Trichogrammatidae) in stored
      cowpea: the effect of distance, time interval, host patch size and spatial
      orientation.
AB  - Host finding and parasitization by Uscana lariophaga Steffan, a potential
      biocontrol agent of the storage pest Callosobruchus maculatus (Fabricius), were
      investigated in stored cowpea. Host finding was shown to be a function of
      distance, time, host patch size and the spatial position of U. lariophaga
      relative to the host patch. Uscana lariophaga females were able to find hosts up
      to 75 cm horizontal distance from the host patch, which was the largest distance
      tested. The probability that a host patch was found when an individual U.
      lariophaga female was released at 2.5 cm horizontal distance from the host patch
      ranged from 0.6 after 2 h foraging time to 0.9 after 8 h foraging time. At 10 cm
      from the host patch, host finding probability ranged from 0.2 to 0.45 at these
      respective foraging times. Finding probabilities doubled compared to horizontal
      distances when U. lariophaga was released below the host patch, and halved when
      it was released above the host patch. The negative geotaxic response was shown
      not to be an artefact of the release method. The median net displacement rate in
      the direction of the host patch was two beans per hour (1.4 cm h(-1)). The
      results suggest that U. lariophaga females start searching for hosts regardless
      of the quality of the olfactory information they receive. Additional observations
      indicated that U. lariophaga is adapted to a host with a patchy distribution,
      which implies that host finding over larger distances is relevant for U.
      lariophaga.

PMID- 15960878
TI  - Laboratory studies of the effects of reduced prey choice caused by Bt plants on a
      predatory insect.
AB  - Crops transformed to express Bacillus thuringiensis (Bt) toxins can cause close
      to 100% mortality of certain target pest species. This study assessed the effect
      of target pest reduction on the predatory insect Chrysoperla carnea (Stephens) in
      the presence of alternative prey. Numbers of lacewings recovered from Bt oilseed
      rape (cultivar Oscar, event O52) did not differ significantly from numbers of
      lacewings recovered from conventional oilseed rape in cage experiments with the
      target pest Plutella xylostella (Linnaeus) and the non-target pest Myzus persicae
      (Sulzer) when aphid densities were high. However, significantly fewer lacewings
      were recovered from Bt plants as aphid densities were lowered. Lacewing weights
      were not affected by plant type.

PMID- 15960879
TI  - Sex separation of tsetse fly pupae using near-infrared spectroscopy.
AB  - Implementation of the sterile insect technique for tsetse (Glossina spp.)
      requires that only sterile male insects be released; thus, at some stage of the
      fly production process the females have to be removed. A further constraint in
      the use of the sterile insect technique for tsetse is that the females are needed
      for colony production and hence, a non-destructive method of sex separation is
      required. In most tsetse sterile insect technique programmes thus far, females
      have been eliminated from the released material by hand-separation of chilled
      adults. Using near-infrared (NIR) spectroscopy, significant differences have been
      found between the spectra for the pupae of male and female G. pallidipes Austen.
      Significantly, the differences appear to be maximized 4-5 days before emergence
      of the adults. Tsetse fly pupae up to five days before emergence can be sexed
      with accuracies that generally range from 80 to 100%. This system, when refined,
      will enable effective separation of male and female pupae to be carried out, with
      emerged females being returned to the colony and males being irradiated and
      released. If separation can be achieved five days before emergence, this will
      also enable irradiated male pupae to be shipped to other destinations as
      required. Other Diptera were evaluated using this system but had lower
      classification accuracies of 50-74%. This may be due to the difference in
      reproductive physiology between these different fly groups.

PMID- 15960880
TI  - Radar studies of the vertical distribution of insects migrating over southern
      Britain: the influence of temperature inversions on nocturnal layer
      concentrations.
AB  - Insects migrating over two sites in southern UK (Malvern in Worcestershire, and
      Harpenden in Hertfordshire) have been monitored continuously with nutating
      vertical-looking radars (VLRs) equipped with powerful control and analysis
      software. These observations make possible, for the first time, a systematic
      investigation of the vertical distribution of insect aerial density in the
      atmosphere, over temporal scales ranging from the short (instantaneous vertical
      profiles updated every 15 min) to the very long (profiles aggregated over whole
      seasons or even years). In the present paper, an outline is given of some general
      features of insect stratification as revealed by the radars, followed by a
      description of occasions during warm nights in the summer months when intense
      insect layers developed. Some of these nocturnal layers were due to the insects
      flying preferentially at the top of strong surface temperature inversions, and in
      other cases, layering was associated with higher-altitude temperature maxima,
      such as those due to subsidence inversions. The layers were formed from insects
      of a great variety of sizes, but peaks in the mass distributions pointed to a
      preponderance of medium-sized noctuid moths on certain occasions.

PMID- 15960881
TI  - Description and behavioural biology of two Ufens species (Hymenoptera:
      Trichogrammatidae), egg parasitoids of Homalodisca species (Hemiptera:
      Cicadellidae) in southern California.
AB  - The morphology, distribution, and hosts of two egg parasitoids, Ufens principalis
      Owen sp. n. and U. ceratus Owen sp. n. (Hymenoptera: Trichogrammatidae), are
      described for the first time. These species are compared to U. niger (Ashmead),
      the only species of Ufens s. str. currently described from the Nearctic, and
      diagnostic differences are presented. The behavioural biology of U. principalis,
      and U. ceratus to a smaller extent, is also described for the first time. Ufens
      principalis exhibited a rapid and long-distance response in the form of
      directional flight toward freshly laid eggs of Homalodisca species, its primary
      hosts in southern California. Parasitism involved aggregations of female U.
      principalis on fresh Homalodisca egg masses, which remained attractive to U.
      principalis for a relatively short time. The level of oviposition by U.
      principalis females was low during most of the day and peaked before sunset in
      tandem with a peak in Homalodisca oviposition. Oviposition behaviour of U.
      principalis is described and the distribution of ovipositor probe durations
      showed that most probes were generally of very short duration. Mating of both
      Ufens species occurred on the egg mass, with males showing aggressive behaviour
      towards each other as they competed for emerging females. Ufens ceratus males
      displayed greater aggression towards other males than U. principalis males. By
      contrast, fights among U. principalis males involved more individuals and lasted
      longer than corresponding fights between U. ceratus males.

PMID- 15960882
TI  - Plastins: versatile modulators of actin organization in (patho)physiological
      cellular processes.
AB  - Many actin-binding proteins are expressed in eukaryotic cells. These polypeptides
      assist in stabilizing and rearranging the organization of the actin cytoskeleton
      in response to external stimuli, or during cell migration and adhesion. Here we
      review a particular set of actin-binding proteins called plastins. Plastins (also
      called fimbrins) belong to a subclass of actin-binding proteins known as actin
      bundling proteins. Three isoforms have been characterized in mammals: T-plastin
      is expressed in cells from solid tissue, whereas L-plastin occurs predominantly
      in hematopoietic cells. The third isoform, I-plastin, is specifically expressed
      in the small intestine, colon and kidney. These proteins share the unique
      property of cross-linking actin filaments into tight bundles. Although plastins
      are primarily involved in regulation of the actin cytoskeleton, they possess some
      unique features. For instance, they are implicated in invasion by pathogenic
      bacteria such as Shigella flexneri and Salmonella typhimurium. Also, L-plastin
      plays an important role in leukocyte function. T-plastin, on the other hand, is
      possibly involved in DNA repair. Finally, both T- and L-plastin are implicated in
      several diseases, and L-plastin is considered to be a valuable marker for cancer.

PMID- 15960883
TI  - Dissecting role of regulatory factors in NF-kappaB pathway with siRNA.
AB  - NF-kappaB, a family of related transcription factors, has been a focus of intense
      scientific research during the past decade. Multiple stimuli, both extracellular
      and intracellular, lead to its activation. The NF-kappaB pathway regulates
      expression of a diverse array of genes involved in different biological
      processes. Various pathological states are characterized by the dysregulated NF
      kappaB pathway. Recently, NF-kappaB activation has been connected with multiple
      aspects of oncogenesis and serves as an important mechanism to regulate cell
      survival in response to chemotherapy by activating different genes that inhibit
      apoptosis. Several methods of inhibiting NF-kappaB activation, such as antisense
      oligonucleotides, proteosome inhibitors and RNA interference (RNAi) are currently
      under investigation. RNAi represents a powerful tool to better define the role of
      specific genes in different signal transduction pathways and has recently been
      used to define the function of genes that regulate the NF-kappaB pathway. This
      review discusses the emerging role of RNAi to dissect the function of regulatory
      factors in the NF-kappaB pathway and its potential use as a targeted therapy.

PMID- 15960884
TI  - Activation of ERK/CREB pathway in spinal cord contributes to chronic constrictive
      injury-induced neuropathic pain in rats.
AB  - AIM: To investigate whether activation and translocation of extracellular signal
      regulated kinase (ERK) is involved in the induction and maintenance of
      neuropathic pain, and effects of activation and translocation of ERK on
      expression of pCREB and Fos in the chronic neuropathic pain. METHODS: Lumbar
      intrathecal catheters were chronically implanted in male Sprague-Dawley rats. The
      left sciatic nerve was loosely ligated proximal to the sciaticaos trifurcation at
      approximately 1.0 mm intervals with 4-0 silk sutures. The mitogen-activated
      protein kinase kinase (MEK) inhibitor U0126 or phosphorothioate-modified
      antisense oligonucleotides (ODN) were intrathecally administered every 12 h, 1 d
      pre-chronic constriction injury (CCI) and 3 d post-CCI. Thermal and mechanical
      nociceptive thresholds were assessed with the paw withdrawal latency (PWL) to
      radiant heat and von Frey filaments. The expression of pERK, pCREB, and Fos were
      assessed by both Western blotting and immunohistochemical analysis. RESULTS:
      Intrathecal injection of U0126 or ERK antisense ODN significantly attenuated CCI
      induced mechanical allodynia and thermal hyperalgesia. CCI significantly
      increased the expression of p-ERK-IR neurons in the ipsilateral spinal dorsal
      horn to injury, not in the contralateral spinal dorsal horn. The time courses of
      pERK expression showed that the levels of both cytosol and nuclear pERK, but not
      total ERK, were increased at all points after CCI and reached a peak level on
      postoperative d 5. CCI also significantly increased the expression of pCREB and
      Fos. Phospho-CREB-positive neurons were distributed in all laminae of the
      bilateral spinal cord and Fos was expressed in laminae I and II of the
      ipsilateral spinal dorsal horn. Intrathecal injection of U0126 or ERK antisense
      ODN markedly suppressed the increase of CCI-induced pERK, pCREB and c-Fos
      expression in the spinal cord. CONCLUSION: The activation of ERK pathways
      contributes to neuropathic pain in CCI rats, and the function of pERK may partly
      be accomplished via the cAMP response element binding protein (CREB)-dependent
      gene expression.

PMID- 15960885
TI  - 6-Hydroxydopamine-induced glutathione alteration occurs via glutathione enzyme
      system in primary cultured astrocytes.
AB  - AIM: To define the role of enzymes involved in glutathione metabolism in 6
      hydroxydopamine (6-OHDA)-induced glutathione alteration in primary cultured
      astrocytes. METHODS: Total glutathione (GSx) levels were determined using the
      modified enzymatic microtiter plate assay. The mRNA levels of gamma
      glutamylcysteine synthetase (gammaGCS), gamma-glutamyltransferase (gammaGT),
      glutathione peroxidase (GPx), GR(glutathione reductase), and glutathione
      transferases (GST) were determined using RT-PCR. gammaGT activity was determined
      using gammaGT assay kits. RESULTS: In primary cultured astrocytes, 6-OHDA induced
      a significant elevation of cellular GSx levels after treatment for 24 h. However,
      the GSx levels decreased after 24 h and the values were even lower than the value
      in the control group without 6-OHDA at 48 h. RT-PCR data showed that the mRNA
      levels of gammaGCS, the rate-limiting enzyme of gamma-L-glutamyl-L
      cysteinylglycine (GSH) synthesis, were increased by 6-OHDA after treatment for 24
      h and 48 h; the mRNA levels of GPx, GR, and GST did not alter in 6-OHDA-treated
      astrocytes after treatment for 24 h and 48 h; and 6-OHDA increased the mRNA
      levels and the activity of gammaGT after treatment for 48 h, which induced a
      decrease in GSx levels, despite the up-regulation of gammaGCS after exposure to 6
      OHDA for 48 h. CONCLUSION: The change in gammaGCS correlated with the increase in
      GSH levels induced by 6-OHDA after treatment for 24 h. GSx levels decreased
      because of increased gammaGT mRNA levels and gammaGT activity induced by 6-OHDA
      after treatment for 48 h.

PMID- 15960886
TI  - Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to
      ischemia in short-term type 1 diabetic rats.
AB  - AIM: To examine the tolerance of type 1 diabetic hearts to ischemia and
      reperfusion injury. Myocardial contents of 27-kDa and 70-kDa heat shock proteins
      (hsp) as well as phosphorylated hsp27 were also determined. METHODS: Hearts from
      hyperglycemic rats 3 weeks after streptozocin injection and age-matched normal
      rats were subjected to ischemia and reperfusion in vitro. Cardiac function and
      electrocardiogram were recorded throughout experiments. Myocardial heat shock
      proteins were detected with Western blot. RESULTS: Despite depressed systolic
      function at the baseline, diabetic hearts exhibited considerable enhancement in
      post-ischemic heart function, manifested by an increase in the maximal rate of
      left ventricular pressure rise and fall (post-ischemic dp/dtmax and dp/dtmin were
      560+/-117 and -313+/-68 mmHg/s in control, n=7, 1249+/-57 and -1204+/-36 mmHg/s
      in diabetes, n=10, P<0.01). Reperfusion ventricular fibrillation in the diabetic
      group were attenuated compared with controls (1.5+/-0.3 vs 7.2+/-2.1 min in
      control, P<0.01). The increased heart resistance to ischemia in diabetes was
      associated with hyperglycemia and accompanied by enhanced expression of
      myocardial phosphorylated hsp27 with normal aortic vessel relaxation.
      Cardioprotection was abrogated by metabolic correction with insulin and
      accompanied by phospho-hsp27 reduction. CONCLUSION: Heart resistance to ischemia
      is increased in type 1 diabetes, and hyperglycemia may present a mild yet
      stressful stimulus leading to upregulation of endogenous stress protein, which
      may play a potential role in cardioprotection and compensate for detrimental
      effects of hyperglycemia in diabetes.

PMID- 15960887
TI  - Isoflurane preconditioning protects against ischemia-reperfusion injury partly by
      attenuating cytochrome c release from subsarcolemmal mitochondria in isolated rat
      hearts.
AB  - AIM: To examine if isoflurane preconditioning can attenuate ischemia/reperfusion
      injury by reducing cytochrome c release from inner mitochondrial membrane.
      METHODS: Isolated hearts of Sprague-Dawley rats were perfused on Langendorff
      apparatus. Hearts were randomly assigned to a non-treated group (CON group, n=12)
      or three isoflurane preconditioning groups (0.5% ISC group, 1.0% ISC group, and
      2.0% ISC group; n=12). In the latter three groups, isoflurane was given at
      concentrations of 0.5%, 1.0%, and 2.0% for 15 min with 15-min washout before 30
      min ischemia. Subsarcolemmal mitochondria of the myocardium were isolated after
      60-min reperfusion. Hemodynamics of the each heart was recorded, infarct size of
      the hearts and contents of cytosolic cytochrome or mitochondrial cytochrome c
      were measured at the end of reperfusion. Morphology of isolated mitochondria in
      the four groups was evaluated, respectively. RESULTS: Compared with the CON
      group, cytosolic cytochrome c in 0.5% ISC group, 1.0% ISC group, and 2.0% ISC
      group were significantly decreased along with a significant increase of
      mitochondrial cytochrome c. Infarct size of the hearts in the four groups were
      56%+/-12%, 41%+/-12%, 32%+/-7% and 33%+/-11%, respectively. The values of the
      three isoflurane preconditioning groups were significantly lower than that of the
      CON group (P<0.05). Isoflurane exposure before ischemia can attenuate the change
      of morphology of mitochondria after reperfusion. The effects of 2.0% isoflurane
      on reducing cytochrome c release were more remarkable than 0.5% and 1.0%
      concentrations of isoflurane. CONCLUSION: Myocardioprotective effects of
      isoflurane preconditioning were associated with attenuation of cytochrome c loss
      from the inner membrane of subsarcolemmal mitochondria.

PMID- 15960888
TI  - Taurine inhibits ischemia/reperfusion-induced compartment syndrome in rabbits.
AB  - AIM: To investigate effects of taurine on ischemia/reperfusion (I/R)-induced
      compartment syndrome in rabbit hind limbs. METHODS: Rabbits underwent femoral
      artery occlusion after ligation of branches from terminal aorta to femoral
      artery. After a 7-h ischemia, reperfusion was established with the use of
      heparinized polyethylene shunts. Rabbits received taurine (1g/kg) or normal
      saline (control) by iv infusion 10 min before shunt placement. During
      reperfusion, anterior compartment pressure (ACP) was monitored continuously in
      the left lower extremity. Gastrocnemius muscle triphenyltetrazolium chloride
      (TTC) level, taurine content and myeloperoxidase activity were assayed. Oxidative
      stress was induced in the in vitro gastrocnemius muscle slices by free radical
      generating systems (FRGS), and the malondialdehyde content was measured in
      presence or absence of taurine. RESULTS: After 7 h of ischemia, none of the
      parameters that we measured were different from those before ischemia, except
      that TTC reduction decreased by 80%. In the control group, after 2 h of
      reperfusion, ACP increased 4.5-fold, and gastrocnemius muscle taurine content was
      reduced by 33%. In taurine-treated animals, at 2h reperfusion, the mean arterial
      blood pressure and heart rate were increased, by 6% and 10%. ACP decreased by
      39%, muscle edema decreased by 16%, TTC reduction increased by 150%, and lactate
      dehydrogenase decreased by 36% compared to control group. Plasma and muscle
      taurine content increased by 70% and 88%, respectively. In the taurine-treated
      group, at 2 h reperfusion, plasma malondialdehyde and conjugated diene content
      were decreased by 38% and 23%, respectively, and muscle malondialdehyde and
      conjugated diene content decreased by 22% and 30%, respectively compared to the
      control group. At 2 h reperfusion, myeloperoxidase activity was increased 3.5
      fold in control animals. In the in vitro study, taurine decreased malondialdehyde
      content in muscle slices incubated with hypochlorous acid in a dose-dependent
      manner, but there was no change when incubated with hydrogen peroxide and
      xanthine oxidase. CONCLUSION: Treatment with taurine inhibited I/R-induced
      compartment syndrome by at least in part attenuating oxidative stress injury
      induced by I/R, suggesting clinical application of taurine might be a new
      strategy for the prevention and treatment of compartment syndrome.

PMID- 15960889
TI  - Effect of hydrogen peroxide on persistent sodium current in guinea pig
      ventricular myocytes.
AB  - AIM: To study the effect of hydrogen peroxide (H2O2) on persistent sodium current
      (I(Na.P)) in guinea pig ventricular myocytes. METHODS: The whole-cell, cell
      attached, and inside-out patch-clamp techniques were applied on isolated
      ventricular myocytes from guinea pig. RESULTS: H2O2 (0.1 mmol/L, 0.5 mmol/L and
      1.0 mmol/L) increased the amplitude of whole-cell I(Na.P) in a concentration
      dependent manner, and glutathione (GSH 1 mmol/L) reversed the increased I(Na.P).
      H2O2 (1 mmol/L) increased persistent sodium channel activity in cell-attached and
      inside-out patches. The mean open probability was increased from control values
      of 0.015+/-0.004 and 0.012+/-0.003 to 0.106+/-0.011 and 0.136+/-0.010,
      respectively (P< 0.01 vs control). They were then decreased to 0.039+/-0.024 and
      0.027+/-0.006, respectively, after the addition of 1 mmol/L GSH (P<0.01 vs H2O2).
      The time when open probability began to increase and reached a maximum was
      shorter in inside-out patches than that in cell-attached patches (4.8+/-1.0 min
      vs 11.5+/-3.9 min, P<0.01; 9.6+/-1.6 min vs 18.7+/-4.7 min, P<0.01). CONCLUSION:
      H2O2 increased the I(Na.P) of guinea pig ventricular myocytes in a concentration
      dependent manner, possibly by directly oxidating the cell membrane.

PMID- 15960890
TI  - Expression of pro-inflammatory and anti-inflammatory cytokines in brain of
      atherosclerotic rats and effects of Ginkgo biloba extract.
AB  - AIM: To study the protein and mRNA expressions of pro-inflammatory and anti
      inflammatory cytokines in the brain of rats with atherosclerosis (AS) and the
      effects of Ginkgo biloba extract (GbE) on expressions of cytokines. METHODS: The
      experimental model of AS in rats were established by intraperitioneal injection
      of vitamin D3 with high fat/cholesterol diet. GbE 100 mg/kg was administered to
      rats by ig. After 8 weeks, the expressions of IL-1beta, TNF-alpha, IL-10, and IL
      10R in the brain tissues of AS rats were detected by enzyme-linked immunosorbant
      assay, immunohistochemistry, Western blotting, and reverse transcriptase
      polymerase chain reaction. RESULTS: The protein and mRNA expressions of IL-1beta,
      TNF-alpha, and IL-10 in the brains were markedly higher in AS groups than that in
      control groups (6.11+/-0.15, 1.55+/-0.14, 0.54+/-0.04 ng/g wet weight vs 0.80+/
      0.14, 0.33+/-0.09, and 0.33+/-0.02 ng/g wet weight, respectively). The protein
      and mRNA expressions of IL-1beta and TNF-alpha in the brains were markedly lower
      in GbE groups (3.82+/-0.54, 0.95+/-0.08 ng/g wet weight) than that in AS groups,
      the protein and mRNA expressions of IL-10 and IL-10R in the brains were markedly
      higher in GbE groups (0.85+/-0.06 ng/g wet weight) than that in AS groups.
      CONCLUSION: GbE inhibited production of pro-inflammatory cytokines IL-1beta and
      TNF-alpha, but up-regulated the production of anti-inflammatory cytokines, IL-10
      and IL-10R in brain, which might be related with its anti-AS actions.

PMID- 15960891
TI  - Genistein inhibits carotid sinus baroreceptor activity in anesthetized male rats.
AB  - AIM: To study the effect of genistein (GST) on carotid baroreceptor activity
      (CBA). METHODS: The functional curve of carotid baroreceptor (FCCB) was
      constructed and the functional parameters of carotid baroreceptor were measured
      by recording sinus nerve afferent discharge in anesthetized male rats with
      perfused isolated carotid sinus. RESULTS: GST at 50, 100, and 200 micromol/L
      inhibited the CBA, which shifted FCCB to the right and downward, with a marked
      decrease in peak slope and peak integral value of carotid sinus nerve discharge
      in a concentration-dependent manner. Pretreatment with 100 micromol/L NG-nitro-L
      arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect the
      effect of GST on CBA. Pretreatment with 500 nmol/L Bay K8644, an agonist of
      calcium channels, could completely abolish the effect of GST on CBA. A potent
      inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L), could
      attenuate the inhibitory effect of GST. CONCLUSION: GST inhibits CBA, and the
      effect may be mediated by protein tyrosine kinase inhibition and a decrease in
      Ca2+ influx through the stretch-activated channels.

PMID- 15960892
TI  - Similar effects on rat renal mesangial cells by expressing different fragments of
      adrenomedullin gene in vitro.
AB  - AIM: To construct pEGFP-N3 recombinant vectors carrying adrenomedullin (AM) or
      fragments of the AM gene, and to express AM or fragments of AM from the pEGFP-N3
      recombinant vectors (pEGFP-N3-AM1-2 and pEGFP-N3-AM1-3) and study their
      biological properties on cultured rat renal mesangial cells (RMC). METHODS: Total
      RNA of rat kidney was obtained using TriZol reagent. The cDNA was synthesized by
      reverse transcriptase using oligo-deoxythymidine as primer. The fragments of AM
      gene were then amplified by polymerase chain reaction (PCR) with specific
      upstream and downstream oligonucleotides. The PCR products were digested with
      EcoRI and BamHI and subcloned into the plasmid pEGFP-N3. Facilitated by cationic
      liposomes, RMC were transfected with pEGFP-N3-AM1-2 or pEGFP-N3-AM1-3. After 24
      h, green fluorescent protein (GFP) fluorescent images were examined with a
      fluorescence microscope. After 48 h, the proliferation of RMC was detected using
      the MTT assay, and the mRNA expression of transforming growth factor-beta1 (TGF
      beta1) was measured by semiquantitative PCR. RESULTS: DNA sequence reports
      verified that pEGFP-N3-AM1-2, which carried the full length AM gene translation
      fragment (preproadrenomedullin preproAM1-185), and pEGFP-N3-AM1-3, which carried
      the translation fragment of preproAM [without adrenotensin (ADT, preproAM150
      185)], were constructed successfully. After 24 h, green fluorescence was observed
      in RMC into which either pEGFP-N3-AM1-2 or pEGFP-N3-AM1-3 was transfected, while
      in the control cells no fluorescence was observed. Either pEGFP-N3-AM1-2 or pEGFP
      N3-AM1-3 delivery inhibited the proliferation of RMC (P<0.01) and decreased the
      mRNA transcription level of TGF-beta1 in RMC (P<0.05). However, no significant
      difference was observed between the effects of pEGFP-N3-AM1-2 and pEGFP-N3-AM1-3.
      CONCLUSION: pEGFP-N3-AM1-2 and pEGFP-N3-AM1-3 were constructed successfully and
      were functionally expressed in RMC. Expressing the fragment of AM without ADT has
      similar inhibitory biological effects on RMS proliferation and TGF-beta1
      transcription with full length preproAM.

PMID- 15960893
TI  - Ischemic preconditioning protects post-ischemic renal function in anesthetized
      dogs: role of adenosine and adenine nucleotides.
AB  - AIM: To investigate the effects of renal ischemic preconditioning (IPC) on both
      renal hemodynamics and the renal interstitial concentrations of adenosine and
      adenine nucleotides induced by ischemia-reperfusion injury. METHODS: Renal
      hemodynamics responses to ischemia-reperfusion injury in mongrel dog models were
      determined with or without multiple brief renal ischemic preconditioning
      treatments, as well as the adenosine A1 receptor antagonist (KW-3902),
      respectively. The renal interstitial concentrations of adenosine and adenine
      nucleotides in response to ischemia-reperfusion injury, either following 1-3
      cycles of IPC or not, were measured simultaneously using microdialysis sampling
      technology. RESULTS: One 10-min IPC, adenosine A1 receptor antagonist (KW-3902)
      also shortened the recovery time of renal blood flow (RBF) and urine flow (UF),
      as well as mean blood pressure (BP). Advanced renal IPC attenuated the increment
      of adenosine and adenine nucleotides, as well as recovery time during the 60-min
      reperfusion which followed the 60-min renal ischemia. All of these recovery times
      were dependent on the cycles of 10-min IPC. The renal interstitial concentrations
      of adenosine and adenine nucleotides increased and decreased during renal
      ischemia and reperfusion, respectively. CONCLUSION: A significant relativity in
      dog models exists between the cycles of 10-min renal IPC and the recovery time of
      BP, UF, and RBF during the 60-min renal reperfusion following 60-min renal
      ischemia, respectively. Renal IPC can protect against ischemia-reperfusion injury
      and the predominant effect of endogenous adenosine induced by prolonged renal
      ischemia; renal adenosine A1 receptor activation during the renal ischemia
      reperfusion injury is detrimental to renal function.

PMID- 15960894
TI  - Interaction effects between estrogen receptor alpha and vitamin D receptor genes
      on age at menarche in Chinese women.
AB  - AIM: To evaluate whether estrogen receptor alpha (ER-alpha) and vitamin D
      receptor (VDR) genes are associated with the age at menarche in Chinese women.
      METHODS: A total of 390 pre-menopausal Chinese women were genotyped at the ER
      alpha PvuII, XbaI, and VDR ApaI loci using polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP). RESULTS: Neither the ER-alpha
      gene nor the VDR gene individually had significant effects on the age at menarche
      in our subjects (P>0.10). However, evidence of interaction effects between the
      two genes were observed: with the aa genotype at the VDR ApaI locus, subjects
      with haplotype PX at the ER-alpha gene had, on average, 6 months later onset of
      menarche than the non-carriers (P=0.01). CONCLUSION: We found that neither the ER
      alpha gene or the VDR gene had a significant association with the age at menarche
      individually. However, potential interaction effects between the two genes were
      observed in Chinese women.

PMID- 15960895
TI  - Design, synthesis, and anti-inflammatory evaluation of a series of novel amino
      acid-binding 1,5-diarylpyrazole derivatives.
AB  - AIM: To design and synthesize a series of novel amino acid-binding 1,5
      diarylpyrazole derivatives, which are intended to act as prodrugs with better
      aqueous solubility than celecoxib, and which will exert potent anti-inflammatory
      activities after being converted to their parent compounds in vivo. METHODS: To
      introduce an amino acid, celecoxib analogs containing amino or methylamino group
      were synthesized first through multi-step chemical reactions. All the synthesized
      compounds were screened in an intact cell-based assay in vitro and in carrageenan
      induced mouse paw edema in vivo. Some active compounds were selected for further
      evaluation in a carrageenan-induced rat paw edema model. The preliminary
      pharmacokinetics experiments were conducted using high performance liquid
      chromatography/mass spectrometry (HPLC/MS). RESULTS: Celecoxib, 6 of the 1,5
      diarylpyrazole class of celecoxib analogs, and their amino acid derivatives
      (hydrochloride salts) were synthesized. In vitro screening, the hydrochloride
      salts showed decreased inhibitory effects on cyclooxygenase (COX)-1 and COX-2
      compared with their parent compounds, but some exhibited potent anti-inflammatory
      activity in vivo. Compound 4a was selected for further evaluation, and its anti
      inflammatory effect was equivalent to that of celecoxib after oral administration
      in the carrageenan-induced rat paw edema model. At three doses (25 mg/kg, 50
      mg/kg, and 100 mg/kg) the percentage inhibition on edema was 20.7%, 52.6%, and
      62.6% (for compound 4a) and 27.8%, 38.4%, and 40.1% (for celecoxib),
      respectively. Preliminary pharmacokinetic evaluations support the hypothesis that
      compound 4a was actually converted to its parent compound, compound 4.
      CONCLUSION: The compound bound with amino acid acts like prodrug, which can exert
      anti-inflammatory effect similar to celecoxib after being converted to its parent
      compound. This finding will be of great benefit in carrying out structural
      modifications of prodrug-like selective COX-2 inhibitors.

PMID- 15960896
TI  - Regulating expressions of cyclin D1, pRb, and anti-cancer effects of deguelin on
      human Burkitt's lymphoma Daudi cells in vitro.
AB  - AIM: To investigate anticancer effects and molecular mechanism of deguelin on
      human Burkittos lymphoma Daudi cells in vitro and compare the cytotoxicities of
      deguelin on Daudi cells and human peripheral blood monocular cells (PBMC).
      METHODS: The effects of deguelin on the growth of Daudi cells were studied by 3
      (4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis
      were detected through Hoechst 33258 staining and Annexin V/PI double-labeled
      cytometry. The effect of deguelin on the cell cycle of Daudi cells were studied
      by a propidium iodide method. The expressions of cyclin D1 and pRb were checked
      by Western blot. RESULTS: The proliferation of Daudi cells were decreased in
      deguelin-treated group with a 24-h IC50 value of 51.55 nmol/L. Deguelin induced
      Daudi cells apoptosis was in a time- and dose-dependent manner. G0/G1 phase
      increased and S phase decreased in Daudi cells treated with deguelin. With
      deguelin 0, 5, 10, 20, and 40 nmol/L treatment for 24 h, G0/G1 phase increased
      from 37.34% to 56.56%, whereas S phase decreased from 37.72% to 21.36%. PBMC was
      less sensitive to the cytotoxic effect of deguelin than Daudi cells. The
      expression of cyclin D1 and pRb protein were decreased sharply in Daudi cells
      treated with deguelin. CONCLUSION: Deguelin is able to inhibit the proliferation
      of Daudi cells by regulating the cell cycle that arrested cells at G0/G1 phase
      and inducing the cell apoptosis. Moreover, deguelin selectively induced apoptosis
      of Daudi cells with low toxicity in PBMC. The antitumor effects of deguelin were
      related to down-regulating the expression of cyclin D1 and pRb protein.

PMID- 15960897
TI  - GLB prevents tumor metastasis of Lewis lung carcinoma by inhibiting tumor
      adhesion actions.
AB  - AIM: To investigate the inhibitory effect of a new compound of GLB on tumor
      metastasis in vivo and analyze its actions on tumor cell adhesion to clarify its
      mechanism. METHODS: The effect of GLB on tumor metastasis was analyzed by Lewis
      lung carcinoma model. The pathological morphology of lung alveolar was evaluated
      by hematoxylin-eosin staining. The effect of GLB on the proliferation of human
      prostate cancer cell (PC-3M, with a high metastatic characteristic) was studied
      using the MTT method, and its actions on PC-3M cell adhesion to human umbilical
      vein endothelial cells (HUVEC) and laminin were analyzed in vitro. RESULTS: GLB
      (100 mg/kg/d for 28 d, ig) reduced the number of lung colonies of Lewis lung
      carcinoma metastasis significantly (P<0.05). Simultaneously, GLB could mitigate
      the damage of lung alveolar caused by metastasic tumor deposits. In vitro, GLB
      inhibited dramatically the adhesion of PC-3M cells to HUVEC (P< 0.01) and laminin
      (P<0.05), without cytotoxic or anti-proliferative action on PC-3M cells.
      CONCLUSION: GLB has anti-tumor metastatic activity, which partly depends on its
      inhibition of tumor adhesion.

PMID- 15960898
TI  - Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear
      translocation of NF-kappaB.
AB  - AIM: To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal
      damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factor
      kappa B (NF-kappaB) family members. METHODS: Female Sprague-Dawley (SD) rats were
      randomly divided into groups: (i), control group; (ii), model group; and (iii),
      TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg
      and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day.
      At 50 days of age, all rats in the model group and drug groups also received a
      single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of
      physiological saline. All rats were killed at different times after MNU or
      physiological saline treatment. The apoptotic index of photoreceptor cells was
      calculated by TUNEL labeling; retinal damage was evaluated based on retinal
      thickness and the expression of NF-kappaB family members was detected by Western
      blot. RESULTS: TMP injections, in a dose-dependent manner, suppressed
      photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As
      compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also
      time-dependently upregulated the NF-kappaB/p65 protein level in the nucleus and
      downregulated the IkappaBalpha protein level in the cytoplasm. However, no
      protective effect of TMP injection on MNU-induced central retinal damage was
      found. CONCLUSION: TMP injection partially protects against MNU-induced retinal
      damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor
      cells apoptosis.

PMID- 15960899
TI  - Phase II metabolites of etofesalamide in filamentous fungi.
AB  - AIM: To study phase II metabolites of etofesalamide in filamentous fungi.
      METHODS: Seven fungi were screened to transform etofesalamide. The metabolites of
      etofesalamide were assayed using liquid chromatography coupled to mass
      spectrometry. The major metabolite was subject to enzymatic hydrolysis to confirm
      its structure. RESULTS: Etofesalamide was converted into two phase II
      metabolites: glucoside and riboside conjugates. Glucoside conjugate was the major
      product with a yield greater than 90%; no phase I metabolites were detected.
      CONCLUSION: Glucoside and riboside conjugations of etofesalamide in filamentous
      fungi differ from the phase II metabolism of glucuronidation in mammals.

PMID- 15960901
TI  - Psychosocial issues in genital herpes management.
AB  - Genital herpes leads to considerable distress in many patients at the time of
      diagnosis. Most people with recurrences adapt psychologically over time, but some
      fail to do so, and show continuing psychological morbidity. It is not clear why
      some people adjust and others do not. Antiviral medication may help to promote
      adjustment but the evidence is inconclusive. Little is known about the
      behavioural adjustments that people make, or how they deal with their sexual
      relationships. Many people fail to disclose to some or all of their sexual
      partners, particularly casual partners. There are little hard data on the most
      effective ways to help people adjust to the diagnosis and to help them to reduce
      the risk of transmission, although what people are told (and the practical advice
      they are offered) may be important. This article, the first of two papers in this
      issue to consider the impact of genital herpes, outlines the problems facing
      people with genital herpes; the second article gives practical guidance for
      clinicians supporting people with herpes.

PMID- 15960902
TI  - Pain following herpes zoster: implications for management.
AB  - At the 11th Annual Meeting of the International Herpes Management Forum (IHMF),
      held 27-29 February 2004, I delivered the Martin Wood Memorial Lecture on the
      management of herpes zoster-associated pain. Prevention of post-herpetic
      neuralgia is an important goal in the management of herpes zoster. Recognition of
      individuals at high risk of progression, followed by prompt intervention with
      antiviral agents, helps to reduce the disability, distress and healthcare
      resource utilization caused by this disease and its consequences. In established
      cases of post-herpetic neuralgia, first line therapy with tricyclic
      antidepressants and second line therapy with some anticonvulsants and opioids
      have both shown efficacy in many patients, but development of more effective
      treatments is needed for optimal outcomes.

PMID- 15960903
TI  - Is viral shedding a surrogate marker for transmission of genital herpes? A
      discussion document.
AB  - While the concept linking herpes simplex virus (HSV) shedding to transmission is
      plausible, few data support shedding as a surrogate marker. If shedding is to be
      used as a surrogate marker in future clinical studies, it must be clear how far
      shedding must be reduced, and what the shape of the transmission:viral load curve
      (or transmission:detection frequency curve) is before transmission is reduced. It
      remains unclear whether peak virus load, frequency of detection of virus, or the
      area under curve of the time:virus load plot is the critical parameter in the
      transmission of HSV. This paper reports on an international meeting of experts
      and a debate at the International Herpes Management Forum (IHMF) Annual Meeting
      (2004), convened to examine whether a surrogate marker for HSV transmission is
      necessary, and whether there is any evidence, either in studies involving HSV or
      other viral infections, to suggest that viral shedding could be used as such a
      surrogate.

PMID- 15960904
TI  - Synergistic interactions between herpes simplex virus type-2 and human
      immunodeficiency virus epidemics.
AB  - Several factors clearly influence HSV-2 transmission, such as female gender and
      number of sexual contacts.3,4 Some are less well defined, and may be confounded
      by other factors, but include time since While the concept linking herpes simplex
      virus (HSV) shedding to transmission is plausible, few data support shedding as a
      surrogate marker. If shedding is to be used as a surrogate marker in future
      clinical studies, it must be clear how far shedding must be reduced, and what the
      shape of the transmission:viral load curve (or transmission:detection frequency
      curve) is before transmission is reduced. It remains unclear whether peak virus
      load, frequency of detection of virus, or the area under curve of the time:virus
      load plot is the critical parameter in the transmission of HSV. This paper
      reports on an international meeting of experts and a debate at the International
      Herpes Management Forum (IHMF) Annual Meeting (2004), convened to examine whether
      a surrogate marker for HSV transmission is necessary, and whether there is any
      evidence, either in studies involving HSV or other viral infections, to suggest
      that viral shedding could be used as such a surrogate.

PMID- 15960905
TI  - Management of CMV infection and disease in transplant patients. 27-29 February
      2004.
AB  - The International Herpes Management Forum (IHMF) has published guidelines for the
      diagnosis and management of cytomegalovirus (CMV) infection and disease in solid
      organ (SOT) and haematopoietic stem cell transplant (HSCT) recipients. These
      recommendations have been updated to include, among others: (1) use of whole
      blood for the polymerase chain reaction (PCR) diagnosis of CMV infection; (2) CMV
      load measurements for prognostication and for monitoring response to anti-CMV
      therapy; (3) valganciclovir prophylaxis in CMV donor-positive/recipientnegative
      (D+/R-) SOT patients for prevention of CMV disease; (4) oral ganciclovir
      prophylaxis, in preference to aciclovir, to reduce incidence of CMV disease in
      SOT patients; (5) pre-emptive therapy with oral ganciclovir to reduce incidence
      of CMV disease and viraemia in liver transplant patients; (6) valaciclovir
      prophylaxis, in preference to high-dose oral aciclovir, to prevent CMV infection
      in allogeneic HSCT patients; and (7) foscarnet as an alternative to intravenous
      ganciclovir for pre-emptive treatment of CMV infection in allogeneic HSCT
      patients. New developments in the field requiring further research were
      highlighted, including: optimal frequency of CMV monitoring in CMV D+/R- SOT
      patients; optimal duration of prophylaxis for the prevention of late CMV disease;
      need for an acceptable viral threshold for initiation of pre-emptive therapy; and
      assessment of the clinical efficacy of valganciclovir for the treatment of CMV
      disease and as pre-emptive therapy in SOT and HSCT patients. This article
      presents supporting evidence for these recommendations and statements.

PMID- 15960906
TI  - Supporting the patient with genital HSV infection.
AB  - How a clinician informs a patient that they have genital herpes, and counsels
      them during diagnosis and treatment, has a critical impact on the patient's long
      term adjustment to herpes. Allowing adequate time for discussion (and ensuring
      that the patient understands the information provided) enables the patient to
      gain sufficient understanding of genital herpes and helps them to adjust well to
      the infection. Support should focus on empowering the patient to take control of
      their disease so that they understand the need to practise safer sex
      consistently, discuss their disease openly with partners, and treat herpes
      outbreaks appropriately. The value of suppressive antiviral therapy and
      consistent condom use to help the patient control their disease, its transmission
      and its psychological sequelae, should not be underestimated.

PMID- 15960907
TI  - Posterior tibial tendon insufficiency: which ligaments are involved?
AB  - BACKGROUND: The pathology manifested in posterior tibial tendon insufficiency
      (PTTI) is not limited to the posterior tibial tendon. The association of ligament
      failure with deformity has been discussed in numerous publications, but extensive
      documentation of the structures involved has not been performed. The purpose of
      this observational study was to identify the pattern of ligament involvement
      using standardized, high-resolution magnetic resonance imaging (MRI) in a series
      of 31 consecutive patients diagnosed with PTTI compared to an age matched control
      group without PTTI. METHOD: The structures evaluated by MRI were the posterior
      tibial tendon, superomedial and inferomedial components of the spring ligament
      complex, talocalcaneal interosseous ligament, long and short plantar ligaments,
      plantar fascia, deltoid ligament, plantar naviculocuneiform ligament, and
      tarsometatarsal ligaments. Structural derangement was graded on a five-part scale
      (0 to IV) with level 0 being normal and level IV indicating a tear of more than
      50% of the cross-sectional area of the ligament. Standard flatfoot measurements
      taken from preoperative plain standing radiographs were correlated with the MRI
      grading system. RESULTS: Statistically significant differences in frequency of
      pathology in the PTTI group and controls were found for the superomedial
      calcaneonavicular ligament (p < 0.0001), inferomedial calcaneonavicular ligament
      (p < 0.0001), interosseous ligament (p = 0.0009), anterior component of the
      superficial deltoid (p < 0.0001), plantar metatarsal ligaments (p = 0.0002) and
      plantar naviculocuneiform ligament (p = 0.0006). The ligaments with the most
      severe involvement were the spring ligament complex (superomedial and
      inferomedial calcaneonavicular ligaments) and the talocalcaneal interosseous
      ligament. CONCLUSION: Ligament involvement is extensive in PTTI, and the spring
      ligament complex is the most frequently affected. Because ligament pathology in
      PTTI is nearly as common as posterior tibial tendinopathy, treatment should seek
      to protect or prevent progressive failure of these ligaments.

PMID- 15960908
TI  - Peroneal tendon subluxation in athletes: fibular groove deepening and retinacular
      reconstruction.
AB  - BACKGROUND: The purpose of this study was to evaluate the results of operative
      treatment of recurrent peroneal tendon dislocations followed by accelerated
      rehabilitation incorporating early range of motion and intermittent
      immobilization. METHODS: Four female and nine male athletes with an average age
      of 24 years had objective clinical evidence of peroneal tendon dislocation (14
      ankles). Operative treatment involved removing a bone flap from the distal
      posterior fibula, deepening the posterior fibular groove, and reattaching the
      bone flap within the deepened groove. The superior peroneal retinaculum also was
      reconstructed. Postoperatively, a removable boot was worn for approximately 4
      weeks, when it was replaced with a stirrup brace. RESULTS: At an average followup
      of 35 months, no recurrent subluxation or dislocation of the peroneal tendons had
      occurred. All patients were able to return to sports by 3 months after surgery.
      Nine of the 14 ankles regained normal range of motion, and the remaining five
      were within 5 degrees of the opposite side. Four patients were completely pain
      free, and nine patients had mild occasional pain that did not limit their
      activities. Eight patients returned to preinjury sports participation, and five
      patients elected to participate in sports at a level lower than they had before
      surgery for reasons not related to their ankle injury. CONCLUSIONS: This
      procedure was reliable for preventing recurrent peroneal tendon instability.
      Range of motion was nearly normal, immobilization time was minimal, and all
      patients returned to daily activities and sports within 3 months of surgery.

PMID- 15960909
TI  - The peroneal groove deepening procedure: a biomechanical study of pressure
      reduction.
AB  - BACKGROUND: The goal of this study was to identify pressure changes throughout
      the peroneal groove after a groove deepening procedure. We hypothesized that
      pressures would decrease. METHODS: Twelve fresh-frozen foot and ankle specimens
      were used. A thin pressure strip containing four sensor pads was secured within
      the peroneal groove with pads 1 through 4 positioned at the calcaneofibular
      ligament (CFL) and at the distal, middle, and proximal groove, respectively. The
      midstance phase of gait was simulated with loads applied to the plantar foot and
      posterior tibial tendon and to the peroneus longus and brevis tendons. Pressures
      were recorded with the ankle in neutral, plantarflexion, dorsiflexion, inversion,
      and eversion. Groove deepening was done by osteotomizing the posterior fibular
      wall. Pressure readings were then recorded. Average pressures for each of the
      four sensor pads after the procedure were compared to those obtained before the
      procedure. RESULTS: The mean pressure overlying the CFL increased at all five
      ankle positions; however, these changes were not significant. Significant
      decreases in pressure were noted within the distal and middle groove at all ankle
      positions after the peroneal groove deepening procedure. Pressure within the
      proximal groove increased at all but one position, with a significant difference
      noted in neutral and plantarflexion. CONCLUSION: Pressures within the middle and
      distal peroneal groove significantly decreased after a groove deepening
      procedure. Combining this technique with peroneal tendon debridement may be
      advantageous for treatment of partial peroneal tendon tears or recalcitrant
      peroneal tendinitis.

PMID- 15960910
TI  - Local bone graft harvested from the distal tibia or calcaneus for surgery of the
      foot and ankle.
AB  - BACKGROUND: Numerous operative procedures around the foot and ankle use bone
      graft to augment healing. Autologous bone graft remains the preferred type for
      these procedures. This can be harvested from the iliac crest, but complications
      are frequent. The purpose of our study was to investigate the option of
      harvesting the bone graft from the ipsilateral distal tibia or calcaneus. METHOD:
      Bone graft was harvested in 114 patients from the distal tibia (70 patients) or
      calcaneus (44 patients). The patients were followed postoperatively for an
      average of 16 (range 5 to 28) months and were evaluated for complications (minor
      and major), satisfaction, and healing rates. RESULTS: There were no major
      complications. Ten patients (8.7%) had minor complications including initial
      incisional sensitivity or local numbness, none of which affected function or
      required additional treatment. Satisfaction rate for the procedure was 100%.
      CONCLUSION: Use of autologous bone graft harvested from the ipsilateral distal
      tibia or calcaneus is a safe and reliable alternative to iliac crest bone graft
      harvest for operative procedures of the foot and ankle.

PMID- 15960911
TI  - The modified distal horizontal metatarsal osteotomy for correction of bunionette
      deformity.
AB  - BACKGROUND: Bunionette is a common deformity for which a number of operative
      procedures have been described. The objective of this study was to evaluate the
      results of a modified distal horizontal metatarsal osteotomy in the correction of
      symptomatic bunionette. METHODS: Metatarsal osteotomies were done in 21 feet in
      14 patients (11 females, three males) with an average age of 44 (range 20 to 67)
      years at the time of operation. The average followup was 32 (range 12 to 52)
      months. RESULTS: The average Lesser Toe Metatarsophalangeal-Interphalangeal Score
      of the American Orthopaedic Foot and Ankle Society increased from 42 points
      (range 24 to 50) preoperatively to 87 points (range 60 to 100) at the last
      followup. The fifth metatarsophalangeal angle averaged 18 degrees (5 to 38
      degrees) preoperatively and 5 degrees (-5 to 26 degrees) at final followup. The 4
      5 intermetatarsal angle averaged 14 degrees (10 to 20 degrees) preoperatively and
      9 degrees (5 to 12 degrees) at final followup. Hardware was removed from two feet
      and scheduled for a third foot because of symptomatic skin irritation.
      CONCLUSIONS: The modified distal horizontal metatarsal osteotomy is a stable and
      reliable method for correction of bunionette. Unsatisfactory results in our
      patients were related to prominent hardware.

PMID- 15960912
TI  - Enhancement of syndesmotic fusion rates in total ankle arthroplasty with the use
      of autologous platelet concentrate.
AB  - BACKGROUND: One of the challenges of total ankle arthroplasty continues to be
      achieving a solid distal fusion of the tibiofibular joint. Delayed union rates of
      29% to 38% and the nonunion rates of 9% to 18% for syndesmotic fusion have been
      documented. The risk of tibial component migration has been reported to increase
      8.5 times if a solid syndesmotic fusion is absent. Growth factors have been shown
      to accelerate bone healing and may enhance the fusion of the syndesmosis and,
      thereby, decrease the frequency of nonunion and subsequent tibial component
      migration. METHODS: An autologous platelet concentrate was used to increase the
      amount of growth factors at the site of the distal tibiofibular joint fusion in
      20 total ankle arthroplasties. RESULTS: Our 6-month fusion rate was 100%. When
      compared to historical controls (6-month fusion rate of 62%) the difference was
      statistically significant (p < 0.0001). CONCLUSION: The improved rate of distal
      tibiofibular fusion may be attributable to the increased presence of growth
      factors provided by an autologous platelet concentrate.

PMID- 15960913
TI  - Ligamentous Lisfranc joint injuries: a biomechanical comparison of dorsal plate
      and transarticular screw fixation.
AB  - BACKGROUND: The current treatment of displaced ligamentous injuries of the
      tarsometatarsal (TMT) joints is open reduction and rigid fixation using
      transarticular screws. This technique causes further articular surface damage
      that theoretically may increase the risk of arthritis. Should the screws break,
      hardware removal is difficult. An alternative method that avoids these potential
      complications is rigid fixation using dorsal plates. METHODS: The displacement
      between the first metatarsal and medial cuneiform, the second metatarsal and
      intermediate cuneiform, the first and second metatarsal bases, and the medial
      cuneiform and second metatarsal base were measured in 10 matched pairs of fresh
      frozen cadaver lower extremities in the unloaded and loaded condition. After
      sectioning the Lisfranc and TMT joint ligaments, measurements were repeated in
      the loaded condition. The first and second TMT joints of the right feet were
      fixed with transarticular 3.5-mm cortical screws while those of the left feet
      with were fixed with dorsal 2.7-mm 1/4 tubular plates. Measurements were then
      repeated in the unloaded and loaded condition. RESULTS: After ligament
      sectioning, significantly increased first and second TMT joint subluxation with
      loading was seen. No significant difference was noted with direct comparison
      between plates and screws with respect to ability to realign the first and second
      TMT joints and to maintain TMT joint alignment during loading. The amount of
      articular surface destruction caused by one 3.5-mm screw was 2.0 +/- 0.7% for the
      medial cuneiform, 2.6 +/- 0.5% for the first metatarsal, 3.6 +/- 1.2% for the
      intermediate cuneiform, and 3.6 +/- 1.0% for the second metatarsal. CONCLUSIONS:
      The model reliably produced displacement of the first and second TMT joints
      consistent with a ligamentous Lisfranc injury. Transarticular screws and dorsal
      plates showed similar ability to reduce the first and second TMT joints after TMT
      and Lisfranc ligament transection and to resist TMT joint displacement with
      weightbearing load. CLINICAL RELEVANCE: Dorsal plating may be an alternative to
      transarticular screws in the treatment of displaced Lisfranc injuries.

PMID- 15960914
TI  - Recurrence potential of diffuse-type giant cell tumor in the foot: radiologic and
      pathologic features.
AB  - BACKGROUND: Aggressive musculoskeletal tumors in the foot, such as diffuse-type
      giant cell tumors or extra-abdominal desmoid tumors, are difficult to treat
      because the foot does not have enough soft tissue to allow wide tumor resection.
      We reviewed the clinical behavior of diffuse-type giant cell tumor in the foot
      and evaluated the recurrence potential of these tumors from radiologic and
      pathologic perspectives. METHODS: Six patients with a mean age of 37.6 years were
      included in this study. Radiologic studies, including sonography, computed
      tomography (CT), magnetic resonance imaging (MRI), and bone and gallium citrate
      scintigraphy, were obtained followed by surgical treatment and histologic
      evaluation of the tumor. RESULTS: Recurrence occurred in three patients. Although
      CT and MRI findings were similar in the recurrent and nonrecurrent tumors, marked
      differences were found between the two by scintigraphy; positive radiotracer
      uptake to the affected foot with gallium citrate scintigraphy was noted only in
      recurrent tumors, although positive accumulation was seen in all patients with
      bone scintigraphy. Histologically, the necrotic area and mitotic activity were
      more apparent in recurrent than in the nonrecurrent tumors, and tumor cell
      dyscohesion was noted in the former, (the intercellular space was increased).
      CONCLUSIONS: Repeated recurrence with tumor invasion into tarsal bone resulted in
      breakage of the tarsal arch that supports the body's weight. Amputation would be
      necessary for patients in whom the disease had progressed to obtain local cure
      and relief of pain. In the present study, we found two features of the recurrence
      potential of diffuse-type giant cell tumors: sparse cell to cell contact on
      pathologic examination and positive accumulation in the tumor on gallium citrate
      scintigraphy. We concluded that giant cell tumors with these two features have a
      strong potential for local recurrence, and thus require intensive followup.

PMID- 15960915
TI  - Results of an Internet survey determining the most frequently used ankle scores
      by AOFAS members.
AB  - BACKGROUND: With technological advances in ankle arthroplasty, there has been
      parallel development in the outcome instruments used to assess the results of
      surgery. The literature recommends the use of valid, reliable, and responsive
      ankle scores, but the ankle scores commonly used in clinical practice remain
      undefined. METHODS: An internet survey of members of the American Orthopaedic
      Foot and Ankle Society (AOFAS) was conducted to determine which three ankle
      scores they perceived as most commonly used in the literature, which ones they
      believe are validated, which ones they prefer, and which they use in practice.
      RESULTS: According to respondents, the three most commonly used scores were the
      AOFAS Ankle score, the Foot Function Index (FFI), and the Musculoskeletal
      Outcomes Data Evaluation and Management System (MODEMS). The respondents believed
      that the AOFAS Ankle score, FFI, and MODEMS were validated. The FFI and MODEMS
      are validated, but the AOFAS ankle score is not validated. CONCLUSIONS: Most
      respondents preferred using the AOFAS Ankle score. The use of the empirical AOFAS
      Ankle score continues among AOFAS members.

PMID- 15960916
TI  - Gait instability in older people with hallux valgus.
AB  - BACKGROUND: Hallux valgus is a common condition that may lead to considerable
      pain and disability. There is also evidence that hallux valgus may impair balance
      and increase the risk of falling in older people. Although a number of plantar
      pressure studies have been undertaken in people with and without hallux valgus,
      little is known about how hallux valgus affects basic gait patterns or the
      movement of the upper body when walking. METHODS: Measurements of temporospatial
      parameters of gait and acceleration patterns of the head and pelvis were obtained
      in 71 people (24 men, 47 women) between 75 and 93 (mean 80 +/- 4) years of age
      when walking on both a level surface and a specially designed irregular walkway.
      Foot problems, vision, peripheral sensation, strength, and reaction time also
      were evaluated. RESULTS: After adjusting for potential confounders, subjects with
      moderate to severe hallux valgus were found to exhibit significantly reduced
      velocity and step length on both walking surfaces and less rhythmic acceleration
      patterns in the vertical plane when walking on the irregular surface compared to
      subjects with no or mild hallux valgus. CONCLUSION: These findings indicate that
      hallux valgus has a significant detrimental impact on gait patterns that may
      contribute to instability and risk of falling in older people, particularly when
      walking on irregular terrain.

PMID- 15960917
TI  - Talocalcaneal coalition: a case showing the ossification process.

PMID- 15960918
TI  - Low-grade central osteosarcoma of the foot and ankle: radiographic and pathologic
      features in two patients: case report and literature review.

PMID- 15960919
TI  - Clinical tip: distraction technique for restoring length of the fibula in ankle
      fractures.

PMID- 15960921
TI  - [Selective sentinel node biopsy in melanoma].

PMID- 15960920
TI  - Clinical and biological aspects of sentinel node biopsy in malignant melanoma--an
      update.
AB  - The diagnostic usefulness of sentinel lymph node biopsy (SLNB) has been well
      established, but its therapeutic value remains unproven. First introduced by
      Morton and colleagues, the SLNB procedure is now widely available, and markedly
      enhances our ability to pathologically stage the regional nodes. Although the SLN
      status is acknowledged as the most powerful indicator of prognosis in melanoma,
      there is no evidence to-date, of survival advantage for complete lymphadenectomy
      in SLN-positive patients. Also, there is no effective adjuvant therapy that could
      benefit these sentinel node-positive patients, as yet. Additionally, new data
      have emerged indicating a possible increase in local/in-transit recurrence
      following complete lymphadenectomy in sentinel node-positive patients. To
      understand fully and to evaluate these observations we need information from
      randomized controlled trials. Major changes have occurred following the latest
      revision of melanoma staging system (AJCC, 6th edition). Concerning N category,
      these include the incorporation of the number of metastatic lymph nodes, the
      tumour burden of nodal metastases, and the ulceration of the primary tumour. The
      data obtained from the new staging system will reflect differences in prognosis
      that were not previously emphasized and which, we hope, will serve as a guide to
      more accurate analysis of metastatic pathways in cutaneous melanoma as well as a
      rationale for new forms of treatment.

PMID- 15960922
TI  - Impact of surgery and chemotherapy on von Willebrand factor and vascular
      endothelial growth factor levels in colorectal cancer.
AB  - INTRODUCTION: von Willebrand factor (vWf) is thought to mediate binding of tumour
      cells to platelets and to favour their systemic spreading capacity. Platelets
      involved in tumour angiogenesis are capable of releasing vascular endothelial
      growth factor (VEGF). Hence, levels of vWf and VEGF may correlate with cancer
      stage. The objectives are determine the impact of surgery and chemotherapy on vWf
      and VEGF in colorectal cancer (CRC) patients. MATERIAL AND METHODS: Twenty
      healthy volunteers (group 1), 14 patients with locally advanced CRC (group 2) and
      12 patients with metastatic CRC (group 3) were enrolled. Blood samples were taken
      at recruitment in group 1, and before and after surgery and chemotherapy in
      groups 2 and 3, respectively. Blood levels of vWf, VEGF, platelet count, C
      reactive protein (CRP), ceruloplasmin and carcinoembrionary antigen (CEA) were
      measured. RESULTS: At baseline, group 3 showed higher concentrations of vWf than
      the other groups (p<0.05). In group 2, vWf became elevated 40% post-surgery
      (p=0.016), independently of changes in CRP or ceruloplasmin. In group 3,
      chemotherapy caused a 42% reduction in VEGF (p=0.015). CONCLUSIONS: There was a
      strong correlation between higher vWf levels and more advanced CRC stage at
      diagnosis. These levels were elevated post-surgery in patients with locally
      advanced CRC. Chemotherapy significantly decreased VEGF in metastatic CRC
      patients before CEA showed any significant change.

PMID- 15960923
TI  - Mutation and homozygous deletion analyses of genes that control the G1/S
      transition of the cell cycle in skin melanoma: p53, p21, p16 and p15.
AB  - INTRODUCTION: The role of genes involved in the control of progression from the
      G1 to the S phase of the cell cycle in melanoma tumors is not fully known.
      MATERIAL AND METHODS: The aims of our study were to analyse alterations in p53,
      p21, p16 and p15 genes in melanoma tumors and melanoma cell lines by single
      strand conformational polymorphism (SSCP), and to detect homozygous deletions. We
      analysed the DNA from 39 patients with primary and metastatic melanomas, and from
      9 melanoma cell lines. RESULTS: The SSCP technique showed heterozygous defects in
      the p53 gene in 8 of 39 (20.5%) melanoma tumors: three point mutations in intron
      sequences (introns 1 and 2) and exon 10, and three new polymorphisms located in
      introns 1 and 2 (C to T transition at position 11701 in intron 1; C insertion at
      position 11818 in intron 2; and C insertion at position 11875 in intron 2). One
      melanoma tumor exhibited two heterozygous alterations in the p16 exon 1 (stop
      codon and missense mutation). No defects were found in the remaining genes.
      Homozygous deletions were more frequent in melanoma cell lines than in melanoma
      tumors in p21, p16 and p15 (22.2%, 44.4%, and 44.4% versus 7.7%, 2.5%, and 5.1%
      respectively). TP53 did not show homozygous deletions. CONCLUSIONS: Our results
      suggest that these genes are involved in melanoma tumorigenesis; but perhaps not
      in the major targets. Other suppressor genes that may be informative of the
      mechanism of tumorigenesis in skin melanomas need to be studied.

PMID- 15960924
TI  - [Bacteraemia risk criteria in the paediatric febrile neutropenic cancer patient].
AB  - INTRODUCTION: Cancer patients with febrile neutropenia are not a homogeneous
      group with respect to risk of bacterial infections. Some authors have proposed
      that febrile cancer patients with low risk factors of bacteraemia could be
      managed at home with domiciliary antibiotic treatment. The objectives are: to
      determine the incidence of bacteraemia in our cancer patients who have febrile
      neutropenia; and to identify the low-risk factors so that the patients can be
      managed at home using domiciliary antibiotic treatment. MATERIAL AND METHODS:
      Clinical review of paediatric haemato-oncology disease admitted to our hospital
      in 2002 suffering from febrile neutropenia. RESULTS: We describe a total of 62
      episodes of febrile neutropenia in 30 patients; 24 episodes in haematology
      patients and 38 episodes in oncology patients. High-risk criteria are age <1
      year, poor bone-marrow recovery, chemotherapy within 10 days of the episode,
      rapid fast neutropenia, leukaemia in relapse, uncontrolled solid cancer, and
      cardiac or nephrology disease. Based on the number of risk-factors, patients with
      two or less risk-factors have an incidence of bacteraemia of 6.7% (1/16) and
      patients with three or more risk factors have an incidence of bacteraemia of
      32.6% (15/46); p<0.05. CONCLUSIONS: Incidence of bacteraemia is similar to the
      reviewed literature; probability of bacteraemia increases with the number of
      individual risk factors, and patients with low risk of bacteraemia could be
      managed on an outpatient basis using domiciliary antibiotic treatment.

PMID- 15960925
TI  - [Paralytic ileus due to vinorelbine].
AB  - Intestinal obstruction is very common in cancer patients and occurs in 80% of
      cases with malignant aetiology. Hence, aggressive treatment is needed in most
      cases. The occlusion can be caused by luminal obstruction, paralysis of the
      intestinal muscle or carcinomatosis with mesentery involvement. The clinical case
      we present is that of a patient diagnosed as having lung cancer and who was
      admitted with paralytic ileus following treatment with vinorelbine; a vinca
      alkaloid whose main characteristic toxicities include neutropenia and peripheral
      neuropathy. Also, on rare occasions, the drug can cause paralysis of the ileum
      due to autonomic neuropathy. Hence, before administering aggressive treatment to
      an occlusive syndrome, cases that could benefit from conservative treatment
      should be ruled out.

PMID- 15960926
TI  - Update on retinoblastoma.

PMID- 15960927
TI  - [Primary melanoma of the rectum: an infrequent neoplasia with an atypical
      presentation].
AB  - Primary anorectal melanoma is a rare malignancy with an extremely aggressive
      biological behaviour. The main clinical presentations are local symptoms such as
      rectal bleeding, anal mass or pain, or a change in bowel habits. The tumour is
      frequently mistaken for benign conditions as haemorrhoids or rectal polyps. Many
      treatments can be used: surgery, chemotherapy, radiotherapy, immunotherapy and
      even bio-therapy. Despite this, the disease has a very poor prognosis and 10% of
      patients survive 5 years.

PMID- 15960928
TI  - Postoperative radiotherapy with simultaneous chemotherapy in high-risk squamous
      cell carcinoma of the head and neck: a novel standard that opens new questions.

PMID- 15960929
TI  - Adjuvant treatment of locally-advanced head and neck tumours.
AB  - Every year about 40,000 new patients are diagnosed as having squamous cell
      carcinoma of the head and neck (HNSCC) and nearly 60% of this population present
      with locally-advanced, but non-metastatic, disease. For many years, radiation
      therapy (RT) alone has been the standard non-surgical treatment for locally
      advanced disease. Nevertheless, even the most effective RT regimens (the once
      daily, hyperfractionation, or accelerated fractionation) show an improvement in
      local control rates of 50%-70% and disease-free survival rates of 30%-40%. These
      modest results have stimulated the search for novel strategies combining RT and
      chemotherapy. Several chemotherapeutic agents have been tested in combination
      with RT and cisplatin appears to be the most powerful agent in the treatment of
      locally-advanced head and neck tumours; as has been demonstrated in a large meta
      analysis and, recently, in two multi-centred randomised trials. Based on these
      results, concurrent chemo-radiotherapy may be considered the standard adjuvant
      treatment for locally-advanced head and neck tumours.

PMID- 15960930
TI  - Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour
      site and stage.
AB  - INTRODUCTION: The need to detect pancreatic cancer at earlier stages is
      undisputed. We recorded the signs and symptoms of patients presenting with
      exocrine pancreatic cancer and evaluated their association with clinical
      characteristics such as tumour site and disease stage. PATIENTS AND METHODS: All
      patients (n = 185) with exocrine pancreatic cancer newly diagnosed at five
      general hospitals in Eastern Spain were prospectively recruited over 5 years.
      Symptoms were elicited through personal interviews and signs were recorded by the
      attending physician on admission. RESULTS: At diagnosis, one third of tumours of
      the pancreas head were in stage I and another third in stage IV. None of the
      tumours of the body and tail were in stage I, and over 80% were in stage IV (p <
      0.001) . At presentation, the most frequent symptoms were asthenia (86%),
      anorexia (85%), weight-loss (85%), abdominal pain (79%), and choluria (59%).
      Cholestatic symptoms were more common in tumours affecting only the pancreatic
      head (p < 0.001) . There was a clear trend toward more localized tumours with
      increasing numbers of cholestatic signs (p < 0.001) . Asthenia, anorexia and
      weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval
      was associated with more advanced stage (p = 0.048). CONCLUSIONS: Proper
      attention to signs and symptoms, especially cholestasis, may help identify
      patients with pancreatic cancer at an earlier stage. Results also provide a
      current picture of the semiology of pancreatic cancer which could be of use in
      studies on the potential of proteomic tests in the early detection of this
      neoplasm.

PMID- 15960931
TI  - [Cost-effectiveness analysis of samario-153 (Quadramet) for the treatment of
      patients with prostate cancer and bone metastases].
AB  - OBJECTIVE: To evaluate the cost-effectiveness of samarium [153Sm-EDTMP]
      (Quadramet) compared to conventional therapy in the treatment of pain in patients
      with prostate cancer and bone metastases. METHOD: A decision tree model for the
      treatment of bone pain due to metastases was adapted to the Spanish context. The
      model represents the standard treatment patterns in Spain for the study
      population. The time-course of the model is 4 months and it computes an estimate
      for the cost of pain control per patient. The effectiveness data for the model
      derive from a randomised trial. The current treatment patterns have been
      established according to the consensus opinions of a group of medical experts.
      RESULTS: The cost of pain control per patient is euro 12,515.39 for conventional
      therapy and euro 5,595.52 for samarium-153 (Quadramet) therapy. The incremental
      cost-effectiveness analysis shows that samarium-153 (Quadramet) is a dominant
      therapy. It presents lower costs and higher efficacy than the conventional
      strategy. The sensitivity analyses showed these results to be robust. CONCLUSION:
      Samarium-153 (Quadramet) is cost-effective in treating pain in patients with
      prostate cancer and bone metastases.

PMID- 15960932
TI  - [Safety and efficacy of oral trans-mucosal fentanyl citrate in the long-term
      treatment of breakthrough pain in oncology patients: the ECODIR study].
AB  - INTRODUCTION: Oral trans-mucosal fentanyl citrate (OTFC) is the one drug
      specifically developed for the management of breakthrough pain. This study
      assesses the long-term safety and efficacy of OTFC standard clinical conditions.
      Patients and methods. Six-month observational study performed on cancer patients
      with episodes of breakthrough pain. Safety was assessed by recording the advent
      of adverse events and efficacy by the evaluating the intensity of breakthrough
      pain. RESULTS: 174 cancer patients were recruited into the study. All adverse
      reactions reported were mild or moderate. OTFC was significantly faster (time to
      the commencement of pain relief: 12.7 +/- 11.4 vs 32.7 +/- 18.4 minutes; p <
      0.001) and potent (post-treatment pain intensity: 3.4 +/- 1.5 vs 4.3 +/- 1.5; p <
      0.001) than the previously-used drugs. CONCLUSIONS: This observational study
      confirms the good safety profile of OTFC as well as its effectiveness over long
      term period treatment of breakthrough pain.

PMID- 15960933
TI  - Cuirasse skin metastases secondary to gastric adenocarcinoma.
AB  - Skin metastases are infrequent manifestations of solid tumours. However, it is
      important to recognize them since they may be the first evidence of a neoplasia,
      or a sign of tumour progression or recurrence. Skin metastases from gastric
      adenocarcinomas are particularly rare, and represent 6% of the total in males and
      1% in females. We report, here, the case of a patient diagnosed with gastric
      adenocarcinoma with extensive subcutaneous infiltration of the abdominal wall,
      resulting in an abdominal cuirass.

PMID- 15960934
TI  - Local recurrence and metastatic disease in a typical N1 carcinoid bronchial
      tumour.
AB  - Typical carcinoid bronchial tumour is a well-known disease that, for years, was
      considered benign. Currently, it is classified within the group of neuro
      endocrine lung tumours. It is a low-grade malignancy tumour with a capability of
      local and distant recurrence. Complete resection with mediastinal lymphadenectomy
      is the treatment-of-choice. There are, usually, long-term survivors, even in
      cases of recurrence or mediastinal node invasion. These patients could benefit
      from removal of recurrent or metastatic disease. We present, here, a case of a 19
      years-old female diagnosed as having N1-bronchial typical carcinoid tumour. She
      underwent radical surgery, but with mediastinal recurrence and hepatic
      metastases. A new radical lung resection was performed, and a liver transplant
      was the therapy-of-choice for the metastatic lesion.

PMID- 15960935
TI  - Embryonic tumours of the central nervous system.

PMID- 15960936
TI  - [Prospective study of the risk factors for the development of post-thrombotic
      syndrome after proximal deep venous thrombosis].
AB  - BACKGROUND AND OBJECTIVE: The incidence and risk factors for the development of
      post-thrombotic syndrome (PTS) are not well known, so the aim of our study is to
      evaluate the development of PTS after proximal deep vein thrombosis (DVT) and its
      relationship with several clinical, laboratory and therapeutic factors. PATIENTS
      AND METHOD: Prospective, observational study. INCLUSION CRITERIA: consecutive
      patients with acute symptomatic proximal DVT in the lower extremities diagnosed
      between February 2000 and July 2002. EXCLUSION CRITERIA: life expectancy < 12
      months, impossibility for follow-up, renal or hepatic failure, previous PTS or
      varicosis and recurrent thrombosis during follow up. Endpoint: PTS at 12 months.
      Explicative variables: clinical risk factors for DVT, D-dimer value,
      hypercoaguable state, anticoagulant therapy and compression stockings compliance.
      Multivariable analysis (logistic regression) was performed. RESULTS: One hundred
      and seventy two patients with DVT were evaluated for inclusion. Sixty nine were
      excluded and 87 patients completed follow-up. PTS appeared in 47 patients (54%).
      Compliance of compression stockings was adequate in 57% of patients and decreased
      45% the risk for PTS (p = 0.01). No significant associations were observed
      between PTS and others variables. Multivariable analysis confirmed the protective
      effect of compression stockings (RR = 0.3; p < 0.01) and previous ipsilateral DVT
      appeared significatively associated with PTS development (RR = 8; p = 0.01)
      CONCLUSIONS: About 50% of patients with proximal DVT develop PTS within 1 year.
      Previous ipsilateral DVT is the strongest risk factor for PTS. Regular
      compression stocking use decreases the risk of PTS by 50%.

PMID- 15960937
TI  - [Incidence and clinical features of patients with comorbidity attended in
      internal medicine areas].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to assess the incidence and clinical
      features of patients with numerous disorders--comorbidity patients (CP)--and to
      clinically validate the CP criteria defined by a panel of experts (patients with
      2 or more chronic diseases, distributed into seven categories). PATIENTS AND
      METHOD: Prospective observational study of all patients, attended in internal
      medicine areas of a tertiary teaching hospital, during June 2003. Patients were
      stratified in 3 cohorts: CP, palliative, and general (GE). Incidence of CP,
      functional evaluation (at baseline, at admission, and at discharge), and burden
      of hospital care (by means of urgent and programmed visits, as well as episodes
      of hospitalization) in the last 12 months were analyzed. A multivariate analysis
      of predictors of survival and functional deterioration (fall in Barthel's scale >
      or = 10 points between baseline-discharge values) was performed in the CP cohort.
      RESULTS: 339 patients (CP cohort: 132; palliative: 52; GE: 155) were included.
      The overall incidence was 38.9/100 admissions/month. CP were older (75 [11] vs 67
      [16]); had higher mortality (19.3% vs 6.1%; relative risk [RR]: 3.66 [95%
      confidence interval [CI], 1.65-8.13]; lower functional ability at baseline (45 vs
      95), at admission (20 vs 75), and at discharge (20 vs 95); higher rates of
      significant functional deterioration (16% vs 7%; RR = 2.47 [95% CI, 1.15-5.35]);
      and required more burden of hospital care by means of urgent care (3.6 [3.4]
      episodes vs 2.4 [1.9]), and hospitalizations (1.9 [1.3] vs 1.5 [1]) than GE
      patients. Chronic digestive/hepatic diseases (odds ratio [OR] = 48.3 [2.4-980.9],
      peripheric vascular disease/diabetes with visceral involvement (OR = 5.6 [CI 95%,
      1.1-28.6]), and better functional ability at admission were associated with
      survival. Female gender (OR ) 46.6 [CI 95%, 4.5-486.9]), chronic lung disease (OR
      = 8.9 [CI 95%, 1.2-64]), and neurologic disease with disability (OR = 8 [CI 95%,
      1.1-58.9]), were associated with significant functional deterioration during
      hospital stay. CONCLUSIONS: The defined CP criteria were highly accurate in
      detecting a population of patients with high attention in Internal Medicine
      areas, high mortality rates, clinical frailty (more need of hospital care), and
      significant functional deterioration. Barthel's scale identified correctly this
      group of patients, and was independently associated with survival.

PMID- 15960938
TI  - [Prevalence of C77G polymorphism in exon 4 of the CD45 gene in the Spanish
      population].
AB  - BACKGROUND AND OBJECTIVE: A mutation (C77G) in exon 4 of the CD45 gene is the
      most common cause of CD45 abnormal splicing in European populations, which has
      been associated with an increased susceptibility to human immunodeficiency virus
      infection. We aimed to analyze the C77G frequency in the Spanish population.
      PATIENTS AND METHOD: 517 healthy donors. CD45RA and RO expression was determined
      in circulating T lymphocytes by flow cytometry. CD45 exon 4 sequencing was
      carried out in individuals with an abnormal coexpression of CD45 isoforms.
      RESULTS: 6/517 individuals presented CD45RA persistence on memory T cells; all of
      them were heterozygous for C77G mutation. The resulting allelic frequency was
      0,58% (95% confidence interval, 0.23-1.32). CONCLUSIONS: C77G is present in the
      Spanish population. Further studies to elucidate its clinical significance are
      needed.

PMID- 15960939
TI  - [Comorbidity patients: the need of a coordinated and global care].

PMID- 15960940
TI  - [International standardization of continuous medical training credits. A peer
      review committee statement].

PMID- 15960941
TI  - [Selective cholesterol absorption inhibition as a new prospect in treatment of
      hypercholesterolemia].
AB  - Ezetimibe is the first of a new class of lipid-lowering drugs, the 2
      azetidinones, which selectively inhibits the absorption of intestinal
      cholesterol. Ezetimibe's mechanism of action complements that of cholesterol
      synthesis inhibitors. Ezetimibe as monotherapy or in combination with statins
      significantly decreases plasma cLDL levels. As monotherapy, ezetimibe is well
      tolerated with a side-effect profile similar to placebo, whereas in combination
      with statins no differences in the incidence of myopathy, rhabdomyolysis or
      elevated liver enzymes are reported.

PMID- 15960942
TI  - [2005 Spanish guidelines in diagnosis and treatment of arterial hypertension].

PMID- 15960943
TI  - [Effectiveness and safety of the treatment with tumour necrosis factor alpha
      antagonists in rheumatoid arthritis patients].

PMID- 15960944
TI  - [Informed or signed consent in stem cell transplantation?].

PMID- 15960945
TI  - [Solitary pleural fibrous tumor: study of 4 cases].

PMID- 15960946
TI  - [Value of the positron emission tomography scan in brain radionecrosis].

PMID- 15960947
TI  - [Infection by Paracoccidioides brasiliensis in an immigrant from Venezuela].

PMID- 15960949
TI  - [Public health surveillance: beyond transmissible diseases].

PMID- 15960950
TI  - [Gaceta Sanitaria and the media: one year later].

PMID- 15960951
TI  - State size as measured in terms of public spending and world health, 1990-2000.
AB  - OBJECTIVE: To determine the relationship between state size (measured in terms of
      public spending) and public health indicators in a sample of countries
      representing all regions of the world and from 1990-2000. METHODS: An ecological
      study was performed using data on Central Government Spending (CGS) and per
      capita Gross National Product (GNP) obtained from the International Monetary
      Fund, and on life expectancy, maternal, and infant mortality, provided by the
      World Health Organization. A multiple linear regression model was fitted to
      estimate the effect of CGS on health, which also took into consideration per
      capita GNP and geographical region. RESULTS: CGS varied little over the study
      period, with convergence around an average of 28%, but within a relatively wide
      range (7.80-53.0%); the countries with the strongest economies (according to per
      capita GNP) had the highest levels of CGS. The influence of this factor was
      particularly relevant for the infant mortality rate (r = 0.40; beta = -1.327; EE
      = 0.237; t = -5.590; p < 0.001). Per capita GNP and geographic location were also
      associated with variations in health; health indicators tended to be worse for
      poorer countries in Africa and Asia. In the adjusted model, CGS was statistically
      significant with regard to infant and maternal mortality rates. CONCLUSION: The
      study suggests that state size (in terms of public spending) has an important
      influence upon health and particularly upon mortality. Although it is important
      to bear in mind the limitations of this study and the reduced time window used,
      these results should be taken into consideration in the current political and
      epidemiological debate.

PMID- 15960952
TI  - [Risk factors surveillance for non-communicable disease through telephone survey.
      Results in the Autonomous Community of Madrid from 1995-2003].
AB  - OBJECTIVE: To illustrate -for the first time with Spanish data- the usefulness of
      telephone-interview-based surveillance of non-communicable diseases risk factors
      for the purpose of drawing up public health policies. METHODS: We analysed
      information from the Non-Communicable Disease Risk Factor Surveillance System
      (Sistema de Vigilancia de Factores de Riesgo asociados a Enfermedades No
      Transmisibles- SIVFRENT) for the period 1995-2003. This system is based on
      monthly telephone interviews covering a representative population sample, aged 18
      64 years. 18,049 interviews were conducted for the whole period. Indicators of
      overweight and obesity, sedentary lifestyle, diet, tobacco and alcohol
      consumption, preventive practices, accidents and injuries, and road safety were
      calculated. The time trend was estimated using average annual prevalence ratios,
      obtained from generalised linear models with binomial family and logarithmic
      link. RESULTS: Among men, the changes of greatest magnitude corresponded to an
      increase in overweight and obesity, which registered a relative annual rise of
      3.7%, and a decrease in dieting (-3%), high alcohol consumption (-6.1%) and non
      use of safety belts (-4%). Among women, there was a marked increase in overweight
      and obesity (3.3%), cessation of smoking (3.1%) and recourse to mammograms
      (6.4%), and a decrease in dieting (-4.1%) and non-use of safety belts (-4.5%).
      CONCLUSIONS: Although important progress was observed in a number of indicators,
      such as tobacco and alcohol consumption, road safety and the undertaking of
      preventive practices, the situation worsened in others, i.e., fundamentally the
      increase in overweight and obesity.

PMID- 15960953
TI  - [Physical activity levels in adults living in Bogota (Colombia): prevalence and
      associated factors].
AB  - OBJECTIVE: To determine the prevalence of physical activity levels in adults aged
      18 to 65 years in Bogota city and identify the factors associated with regular
      physical activity. METHODS: We conducted a population-based, cross-sectional
      survey in 3,000 adult residents of Bogota in 2003 who were selected through a
      multistage probabilistic sample. Physical activity levels were determined using
      the short version of the International Physical Activity Questionnaire. Factors
      associated with regular physical activity were identified by logistic regression
      models. RESULTS: The adjusted prevalence of persons undertaking regular physical
      activity was 36.8%. After adjustment for potential confounders, regular physical
      activity was more likely in men (odds ratio [OR] = 1.62; 95% CI, 1.31-2.01) and
      in those whose self-perceived health status was good or very good (OR = 1.87; 95%
      CI, 1.41-2.49) and was less likely in those aged 30-49 years or 50-65 years (OR =
      0.78; 95% CI, 0.63-0.96, and OR = 0.60; 95% CI, 0.43-0.82, respectively) and in
      those whose main activity in the previous 30 days was searching for a job (OR =
      0.71; 95% CI, 0.51-0.97) or carrying out household tasks (OR = 0.72; 95% CI, 0.54
      0.96). In women, unlike men, age groups showed no association with regular
      physical activity. CONCLUSION: This study shows gender differences in the
      prevalence of physical activity levels and associated factors. Future studies
      should establish, in the context of Latin American cities, whether it is
      appropriate to determine specific measures in each domain, in addition to overall
      physical activity levels.

PMID- 15960954
TI  - [Outbreak of 18 cases of hepatitis C in a hemodialysis unit].
AB  - OBJECTIVES: On September 30, 2001 we had notice of a probable outbreak of
      hepatitis C virus (HCV) infection in a hemodialysis unit in Ciudad Real (Spain).
      We conducted an investigation of the outbreak to determine its cause and
      implement control measures. METHODS: We performed a descriptive study and another
      analytic study (retrospective cohort study). In the descriptive study, the
      incidence of HCV infection in the unit between 01/01/98 and 09/30/01 was studied.
      In the cohort study, 86 subjects were included, of which 18 were infected with
      HCV during the outbreak. Virologic study was performed, including serology of
      anti-HCV antibodies, specific IgG avidity study, polymerase chain reaction and
      phylogenetic analysis of the viral subtypes found. RESULTS: In the study period,
      there were 86 patients under treatment in the hemodialysis unit, of which 27
      (31.4%) were HCV-positive before 03/01/01. The epidemic curve suggested a common
      source with secondary cases. Since 1998 only one seroconversion had been
      documented (in 1999). Statistically significant differences were found only for
      the variable of dialysis shift. None of the patients who underwent dialysis on
      the Tuesday-Saturday-Thursday shift exclusively was infected. All cases were
      genosubtype 4d, which is uncommon in Spain (accounting for 3%), suggesting a
      common initial source for all cases. Most of the previous cases of HCV in the
      hemodialysis unit were 1b; three were 4c/4d and one was 1a. The IgG avidity study
      suggested that not all the cases were infected at the same time, supporting the
      hypothesis of a common source with secondary spread. CONCLUSIONS: The outbreak of
      HCV was confirmed, with 18 cases among dialyzed patients in the central unit. The
      outbreak was caused by the same viral strain, probably due to a common source
      with secondary person-to-person transmission among the patients.

PMID- 15960955
TI  - [Automatization of a hospital-based tumor registry].
AB  - INTRODUCTION: To increase data reliability and reduce the costs associated with
      the HTR, the Catalan Institute of Oncology programmed the manual procedures of
      data collection from databases by means of a computer application (ASEDAT).
      MATERIAL AND METHOD: ASEDAT detects the incident tumors of the registry from the
      databases of the pathology records (PR) and discharge records (DR) and selects
      the basic information from both databases. Data from the HTR data was collected
      for the period 1999-2000 by means of 2 procedures: manual and automatized
      collection and the results obtained were compared. RESULTS: 10,498 cancer
      patients were detected. Manual resolution detected 8,309 incident tumors and
      2,374 prevalent tumors. ASEDAT automatically detected 8,901 patients (84.8%), in
      whom 8,367 incident tumors were detected (58 more tumors than the manual
      procedure). Validation of agreement was performed in the incident tumors detected
      by both methods (7,063 tumors). In 6,185 tumors (87.6%) the information agreed in
      all the variables. Of the discordant tumors, 692 (9.8%) were obtained by the RHT
      staff using manual resolution, and the remainder (186; 2.6%) were obtained by the
      application (automatic resolution). CONCLUSIONS: Cancer registry automatization
      is feasible when PR and DR databases are available, coded and automatized.

PMID- 15960956
TI  - [Prescription of cyclooxygenase-2 inhibitors: an intervention strategy in primary
      care].
AB  - OBJECTIVE: To evaluate an intervention designed to rationalize prescription of
      nonsteroidal anti-inflammatory drugs (NSAIDs), especially cyclooxygenase-2
      inhibitors (COXIBs). SUBJECTS AND METHODS: We performed a before-after
      intervention study. Face-to-face educational outreach visits were conducted in
      general practitioners who were heavy prescribers and group intervention for the
      remaining. Data on prescribing habits were obtained from the pharmacy database of
      the Catalan Health Institute. The pre-intervention period (period 1) was compared
      with the immediate postintervention period (period 2, which coincided with the
      publication of a safety alert on the adverse effects of COXIBs) and the late
      postintervention period (period 3). The data monitored were: a) expenditure due
      to COXIBs; b) consumption in daily defined doses (DDD) per 1,000 habitants/day
      (DHD); c) the percentage of COXIBs/total NSAIDs and the percentage of recommended
      NSAIDs/total NSAIDs, and d) the mean daily cost of DHD of NSAIDs. RESULTS: The
      mean monthly reduction in expenditure on COXIBs was 19,480 euro/month in period 2
      and was 18,555 euro/month in period 3. The percentage of reduction in DHD of
      COXIBs was 35.4% (p < 0.001), which remained stable throughout the study. The
      percentage of recommended NSAIDs/total NSAIDs increased 14% in the short term and
      17% in the long term while the mean daily cost was reduced by 10.1% and 11.2%.
      The decrease in DHD of COXIBs in the face-to-face intervention group was 39.5% in
      period 2 and was 42.2% period 3 compared with 19.4% and 12.4% in the group
      intervention. CONCLUSIONS: The educational intervention was associated with
      improvements in prescription of NSAIDs, although some of the improvement was
      probably due to the safety alert issued during the study period.

PMID- 15960957
TI  - [Commentary: complexities in the evaluation of complex interventions].

PMID- 15960958
TI  - [Trends in mortality from homicide in Medellin (Colombia): 1975-2003].
AB  - OBJECTIVE: To describe and evaluate homicide mortality trends in the city of
      Medellin, Colombia, between 1975 and 2003. METHOD: Deaths from homicide between
      January, 1975 and December, 2003 were studied. With the aid of the SSS1 program,
      an analysis of temporary series was run using iterative procedures for ARIMA
      model construction. RESULTS: The mean monthly homicide mortality rate was 13.2 x
      10(5) (minimum 1.94 February 1977 and maximum 38.78 December 1992). A peak was
      observed in the central period of the series. Several models were studied and an
      ARIMA (0,1,1)(0,0,1)12 model was selected. CONCLUSIONS: Marked annual seasonal
      variation was found in mortality from homicide in the city of Medellin. The
      highest rates were found in the month of December.

PMID- 15960959
TI  - [Collective participation and the elicitation of preferences for health care
      programs: a health system perspective].
AB  - The need to increase collective participation in health care decision-making is
      one of the main health reform issues in publicly financed health systems. The
      present article examines the arguments for collective participation, the means
      for improving it and the methods available to elicit collective preferences
      concerning health programs to be financed by the health system. We review the
      various collective participation tools, as well as the preference elicitation
      methods assist priority setting in collectively funded health care systems.
      Finally, the paper suggests some policy implications for policy making design in
      Spain.

PMID- 15960960
TI  - [Surveillance of environmental risks in public health. The case of air
      pollution].

PMID- 15960961
TI  - [Publish or perish? Challenges in biomedical publishing].

PMID- 15960962
TI  - [Health advocacy in violence against women: an experience].
AB  - The development of political responses to a problem needs for its construction as
      a social problem of a continuous epidemiological surveillance system available
      for the affected public and key decision makers. A women's health advocacy net
      based initiative was launched in November 2003. Every month the epidemic index of
      deaths (ratio of deaths in that month and median of deaths occurring the previous
      5 years) due to Intimate Partner Violence (IPV) is published in a section called
      "Violence Alert" of e-leusis.net a women's web page. The objective was giving
      visibility to information contributing to shape the problem. from a population
      perspective. The initiative was introduced at the beginning to journalists and
      every month a press release with the index results and a comment on it is
      circulated. More than half of the months studied (January 2003-December 2004)
      were epidemic (epidemic indexb > or = 1.25). "Violence alert" has received 2330
      visits since then, an average of 65 visits per week. The page attracted media
      coverage from radio, TV and newspapers.

PMID- 15960964
TI  - [Acarbose for the treatment of impared glucose tolerance?].

PMID- 15960966
TI  - Stem cells for lung cancer?
AB  - Stem cells are believed to be crucial players in tumor development. There is much
      interest in identifying those compartments that harbor stem cells involved in
      lung cancer, given the high incidence and recurrence rate of this disease. In
      this issue of Cell, Kim and colleagues describe a niche in the bronchioalveolar
      duct junction of adult mouse lung that harbors stem cells from which
      adenocarcinomas are likely to arise. They enriched, propagated, and
      differentiated these stem cells in vitro and found that they were activated by
      the oncogenic protein K-ras. This study provides exciting insights into how the
      stem cell compartment operates during both normal lung-tissue homeostasis and the
      development of lung cancer. The new work offers perspectives on possible
      therapeutic interventions to combat lung cancer.

PMID- 15960967
TI  - RNA interference libraries prove their worth in hunt for tumor suppressor genes.
AB  - RNA interference has been promoted as an ideal tool for functional genomics, but
      to date the success stories have principally been in model organisms. Two papers
      in this issue of Cell change all that: use of RNA interference libraries
      targeting large proportions of the human genome to uncover two novel tumor
      suppressor genes. REST is a transcriptional repressor that silences neuron
      specific gene expression, and PITX1 is a homeodomain transcription factor that
      promotes the expression of a negative regulator of Ras.

PMID- 15960968
TI  - Getting downstream without a Raft.
AB  - The role of plasma-membrane microdomains in the organization of signaling
      proteins has been a controversial topic in T cell signaling. In this issue of
      Cell, use of single-molecule fluorescence suggests that protein-protein
      interactions, not detergent insolubility, regulate the assembly of signaling
      complexes in the plasma membrane.

PMID- 15960969
TI  - Anchors away! Fos fosters anchor-cell invasion.
AB  - Invasion of cells through breakdown of the basement membrane is a crucial step
      during development and cancer metastasis. In this issue of Cell, simple and
      genetically tractable cellular assay in the worm for elucidating the molecular
      processes that underlie cell invasion in vivo is described. They demonstrate that
      the transcription factor Fos is required for cell invasion and identify three of
      its downstream target genes (encoding a matrix metalloproteinase, hemicentin, and
      a fat-like protocadherin).

PMID- 15960970
TI  - Auxin distribution and plant pattern formation: how many angels can dance on the
      point of PIN?
AB  - The plant hormone auxin is central in patterning diverse plant tissues. The
      direction of auxin flow and the distribution of auxin within tissues are
      regulated by auxin efflux transporters that are polarly localized in cells.
      Feedback regulation between auxin and its transporters establishes homeostatic
      patterns of auxin accumulation but allows dynamic repatterning in response to
      developmental or environmental cues.

PMID- 15960971
TI  - Identification of bronchioalveolar stem cells in normal lung and lung cancer.
AB  - Injury models have suggested that the lung contains anatomically and functionally
      distinct epithelial stem cell populations. We have isolated such a regional
      pulmonary stem cell population, termed bronchioalveolar stem cells (BASCs).
      Identified at the bronchioalveolar duct junction, BASCs were resistant to
      bronchiolar and alveolar damage and proliferated during epithelial cell renewal
      in vivo. BASCs exhibited self-renewal and were multipotent in clonal assays,
      highlighting their stem cell properties. Furthermore, BASCs expanded in response
      to oncogenic K-ras in culture and in precursors of lung tumors in vivo. These
      data support the hypothesis that BASCs are a stem cell population that maintains
      the bronchiolar Clara cells and alveolar cells of the distal lung and that their
      transformed counterparts give rise to adenocarcinoma. Although bronchiolar cells
      and alveolar cells are proposed to be the precursor cells of adenocarcinoma, this
      work points to BASCs as the putative cells of origin for this subtype of lung
      cancer.

PMID- 15960972
TI  - A genetic screen for candidate tumor suppressors identifies REST.
AB  - Tumorigenesis is a multistep process characterized by a myriad of genetic and
      epigenetic alterations. Identifying the causal perturbations that confer
      malignant transformation is a central goal in cancer biology. Here we report an
      RNAi-based genetic screen for genes that suppress transformation of human mammary
      epithelial cells. We identified genes previously implicated in proliferative
      control and epithelial cell function including two established tumor suppressors,
      TGFBR2 and PTEN. In addition, we uncovered a previously unrecognized tumor
      suppressor role for REST/NRSF, a transcriptional repressor of neuronal gene
      expression. Array-CGH analysis identified REST as a frequent target of deletion
      in colorectal cancer. Furthermore, we detect a frameshift mutation of the REST
      gene in colorectal cancer cells that encodes a dominantly acting truncation
      capable of transforming epithelial cells. Cells lacking REST exhibit increased
      PI(3)K signaling and are dependent upon this pathway for their transformed
      phenotype. These results implicate REST as a human tumor suppressor and provide a
      novel approach to identifying candidate genes that suppress the development of
      human cancer.

PMID- 15960973
TI  - A genetic screen identifies PITX1 as a suppressor of RAS activity and
      tumorigenicity.
AB  - Activating mutations of RAS frequently occur in subsets of human cancers,
      indicating that RAS activation is important for tumorigenesis. However, a large
      proportion of these cancers still retain wild-type RAS alleles, suggesting that
      either the RAS pathway is activated in a distinct manner or another pathway is
      deregulated. To uncover novel tumor-suppressor genes, we screened an RNA
      interference library for knockdown constructs that transform human primary cells
      in the absence of ectopically introduced oncogenic RAS. Here we report the
      identification of PITX1, whose inhibition induces the RAS pathway and
      tumorigenicity. Interestingly, we observed low expression of PITX1 in prostate
      and bladder tumors and in colon cancer cell lines containing wild-type RAS.
      Restoration of PITX1 in the colon cancer cells inhibited tumorigenicity in a wild
      type RAS-dependent manner. Finally, we identified RASAL1, a RAS-GTPase-activating
      protein, as a transcription target through which PITX1 affects RAS function.
      Thus, PITX1 suppresses tumorigenicity by downregulating the RAS pathway through
      RASAL1.

PMID- 15960974
TI  - WDR5 associates with histone H3 methylated at K4 and is essential for H3 K4
      methylation and vertebrate development.
AB  - Histone H3 lysine 4 (K4) methylation has been linked to the transcriptional
      activation in a variety of eukaryotic species. Here we show that a common
      component of MLL1, MLL2, and hSet1 H3 K4 methyltransferase complexes, the WD40
      repeat protein WDR5, directly associates with histone H3 di- and trimethylated at
      K4 and with H3-K4-dimethylated nucleosomes. WDR5 is required for binding of the
      methyltransferase complex to the K4-dimethylated H3 tail as well as for global H3
      K4 trimethylation and HOX gene activation in human cells. WDR5 is essential for
      vertebrate development, in that WDR5-depleted X. laevis tadpoles exhibit a
      variety of developmental defects and abnormal spatial Hox gene expression. Our
      results are the first demonstration that a WD40-repeat protein acts as a module
      for recognition of a specific histone modification and suggest a mechanism for
      reading and writing an epigenetic mark for gene activation.

PMID- 15960975
TI  - Physical association and coordinate function of the H3 K4 methyltransferase MLL1
      and the H4 K16 acetyltransferase MOF.
AB  - A stable complex containing MLL1 and MOF has been immunoaffinity purified from a
      human cell line that stably expresses an epitope-tagged WDR5 subunit. Stable
      interactions between MLL1 and MOF were confirmed by reciprocal
      immunoprecipitation, cosedimentation, and cotransfection analyses, and
      interaction sites were mapped to MLL1 C-terminal and MOF zinc finger domains. The
      purified complex has a robust MLL1-mediated histone methyltransferase activity
      that can effect mono-, di-, and trimethylation of H3 K4 and a MOF-mediated
      histone acetyltransferase activity that is specific for H4 K16. Importantly, both
      activities are required for optimal transcription activation on a chromatin
      template in vitro and on an endogenous MLL1 target gene, Hox a9, in vivo. These
      results indicate an activator-based mechanism for joint MLL1 and MOF recruitment
      and targeted methylation and acetylation and provide a molecular explanation for
      the closely correlated distribution of H3 K4 methylation and H4 K16 acetylation
      on active genes.

PMID- 15960976
TI  - Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund
      Thomson syndrome.
AB  - How the replication machinery is loaded at origins of DNA replication is poorly
      understood. Here, we implicate in this process the Xenopus laevis homolog (xRTS)
      of the RECQL4 helicase mutated in Rothmund-Thomson syndrome. xRTS, which bears
      homology to the yeast replication factors Sld2/DRC1, is essential for DNA
      replication in egg extracts. xRTS can be replaced in extracts by its human
      homolog, while RECQL4 depletion from mammalian cells induces proliferation
      failure, suggesting an evolutionarily conserved function. xRTS accumulates on
      chromatin during replication initiation, after prereplication-complex (pre-RC)
      proteins, Cut5, Sld5, or Cdc45 but before replicative polymerases. xRTS depletion
      suppresses the loading of RPA, the ssDNA binding protein that marks unwound
      origins before polymerase recruitment. However, xRTS is unaffected by xRPA
      depletion. Thus, xRTS functions after pre-RC formation to promote loading of
      replication factors at origins, a previously unrecognized activity necessary for
      initiation. This role connects defective replication initiation to a chromosome
      fragility disorder.

PMID- 15960977
TI  - Chromosome and replisome dynamics in E. coli: loss of sister cohesion triggers
      global chromosome movement and mediates chromosome segregation.
AB  - Chromosome and replisome dynamics were examined in synchronized E. coli cells
      undergoing a eukaryotic-like cell cycle. Sister chromosomes remain tightly
      colocalized for much of S phase and then separate, in a single coordinate
      transition. Origin and terminus regions behave differently, as functionally
      independent domains. During separation, sister loci move far apart and the
      nucleoid becomes bilobed. Origins and terminus regions also move. We infer that
      sisters are initially linked and that loss of cohesion triggers global chromosome
      reorganization. This reorganization creates the 2-fold symmetric, ter-in/ori-out
      conformation which, for E. coli, comprises sister segregation. Analogies with
      eukaryotic prometaphase suggest that this could be a primordial segregation
      mechanism to which microtubule-based processes were later added. We see no long
      lived replication "factory"; replication initiation timing does not covary with
      cell mass, and we identify changes in nucleoid position and state that are
      tightly linked to cell division. We propose that cell division licenses the next
      round of replication initiation via these changes.

PMID- 15960978
TI  - Multiple mechanisms confining RNA polymerase II ubiquitylation to polymerases
      undergoing transcriptional arrest.
AB  - In order to study mechanisms and regulation of RNA polymerase II (RNAPII)
      ubiquitylation and degradation, highly purified factors were used to reconstitute
      RNAPII ubiquitylation in vitro. We show that arrested RNAPII elongation complexes
      are the preferred substrates for ubiquitylation. Accordingly, not only DNA-damage
      dependent but also DNA-damage-independent transcriptional arrest results in
      RNAPII ubiquitylation in vivo. Def1, known to be required for damage-induced
      degradation of RNAPII, stimulates ubiquitylation of RNAPII only in an elongation
      complex. Ubiquitylation of RNAPII is dependent on its C-terminal repeat domain
      (CTD). Moreover, CTD phosphorylation at serine 5, a hallmark of the initiating
      polymerase, but not at serine 2, a hallmark of the elongating polymerase,
      completely inhibits ubiquitylation. In agreement with this, ubiquitylated RNAPII
      is hypophosphorylated at serine 5 in vivo, and mutation of the serine 5
      phosphatase SSU72 inhibits RNAPII degradation. These results identify several
      mechanisms that confine ubiquitylation of RNAPII to the forms of the enzyme that
      arrest during elongation.

PMID- 15960979
TI  - Activation-loop autophosphorylation is mediated by a novel transitional
      intermediate form of DYRKs.
AB  - Autophosphorylation of a critical residue in the activation loop of several
      protein kinases is an essential maturation event required for full enzyme
      activity. However, the molecular mechanism by which this happens is unknown. We
      addressed this question for two dual-specificity tyrosine-phosphorylation
      regulated protein kinases (DYRKs), as they autophosphorylate their activation
      loop on an essential tyrosine but phosphorylate their substrates on serine and
      threonine. Here we demonstrate that autophosphorylation of the critical
      activation-loop tyrosine is intramolecular and mediated by the nascent kinase
      passing through a transitory intermediate form. This DYRK intermediate differs in
      residue and substrate specificity, as well as sensitivity to small-molecule
      inhibitors, compared with its mature counterpart. The intermediate's
      characteristics are lost upon completion of translation, making the critical
      tyrosine autophosphorylation a "one-off" inceptive event. This mechanism is
      likely to be shared with other kinases.

PMID- 15960982
TI  - Molecular properties and prebiotic effect of inulin obtained from artichoke
      (Cynara scolymus L.).
AB  - A high molecular weight inulin has been prepared from artichoke (Cynara scolymus
      L.) agroindustrial wastes using environmentally benign aqueous extraction
      procedures. Physico-chemical analysis of the properties of artichoke inulin was
      carried out. Its average degree of polymerization was 46, which is higher than
      for Jerusalem artichoke, chicory, and dahlia inulins. GC-MS confirmed that the
      main constituent monosaccharide in artichoke inulin was fructose and its
      degradation by inulinase indicated that it contained the expected beta-2,1
      fructan bonds. The FT-IR spectrum was identical to that of chicory inulin. These
      data indicate that artichoke inulin will be suitable for use in a wide range of
      food applications. The health-promoting prebiotic effects of artichoke inulin
      were demonstrated in an extensive microbiological study showing a long lasting
      bifidogenic effect on Bifidobacterium bifidum ATCC 29521 cultures and also in
      mixed cultures of colonic bacteria.

PMID- 15960980
TI  - Single-molecule microscopy reveals plasma membrane microdomains created by
      protein-protein networks that exclude or trap signaling molecules in T cells.
AB  - Membrane subdomains have been implicated in T cell signaling, although their
      properties and mechanisms of formation remain controversial. Here, we have used
      single-molecule and scanning confocal imaging to characterize the behavior of GFP
      tagged signaling proteins in Jurkat T cells. We show that the coreceptor CD2, the
      adaptor protein LAT, and tyrosine kinase Lck cocluster in discrete microdomains
      in the plasma membrane of signaling T cells. These microdomains require protein
      protein interactions mediated through phosphorylation of LAT and are not
      maintained by interactions with actin or lipid rafts. Using a two color imaging
      approach that allows tracking of single molecules relative to the CD2/LAT/Lck
      clusters, we demonstrate that these microdomains exclude and limit the free
      diffusion of molecules in the membrane but also can trap and immobilize specific
      proteins. Our data suggest that diffusional trapping through protein-protein
      interactions creates microdomains that concentrate or exclude cell surface
      proteins to facilitate T cell signaling.

PMID- 15960981
TI  - FOS-1 promotes basement-membrane removal during anchor-cell invasion in C.
      elegans.
AB  - Cell invasion through basement membranes is crucial during morphogenesis and
      cancer metastasis. Here, we genetically dissect this process during anchor-cell
      invasion into the vulval epithelium in C. elegans. We have identified the fos
      transcription factor ortholog fos-1 as a critical regulator of basement-membrane
      removal. In fos-1 mutants, the gonadal anchor cell extends cellular processes
      normally toward vulval cells, but these processes fail to remove the basement
      membranes separating the gonad from the vulval epithelium. fos-1 is expressed in
      the anchor cell and controls invasion cell autonomously. We have identified ZMP
      1, a membrane-type matrix metalloproteinase, CDH-3, a Fat-like protocadherin, and
      hemicentin, a fibulin family extracellular matrix protein, as transcriptional
      targets of FOS-1 that promote invasion. These results reveal a key genetic
      network that controls basement-membrane removal during cell invasion.

PMID- 15960983
TI  - Crotonic acid as a bioactive factor in carrot seeds (Daucus carota L.).
AB  - Water extracts from the carrot seed (Daucus carota L.) var. Perfekcja exhibit
      plant growth inhibitory properties against cress, cucumber, onion and carrot in a
      dose-dependant manner. This property results from the action of low-and high
      molecular components of the extract. The low-molecular component was identified
      as crotonic acid ((E)-2-butenoic acid). Its presence was also confirmed in other
      late varieties of carrot. The determined strong herbicidal properties of crotonic
      acid and its availability after release to soil combined with its high level in
      seeds suggest that it might be considered as an allelopathic and autotoxic factor
      in the seeds.

PMID- 15960985
TI  - The Netrin family of guidance factors: emphasis on Netrin-1 signalling.
AB  - During the development of the nervous system, neurons respond to the coordinated
      action of a variety of attractive and repulsive signals from the embryonic
      environment. Netrins form a family of extracellular proteins that regulate the
      migration of neurons and axonal growth cones. These proteins are bifunctional
      signals that are chemoattractive for some neurons and chemorepellent for others.
      Netrins mainly interact with the specific receptors DCC and UNC-5 family. To
      date, several Netrins have been described in mouse and humans: Netrin-1, -3/NTL2,
      -4/beta and G-Netrins. Netrin-1 is the most studied member of the family. It is
      involved in the development many projections of the nervous system. When Netrin-1
      interacts with its specific receptors, a cascade of local cytoplasmic events is
      triggered. Several signal transduction pathways and effector molecules have been
      implicated in the response to Netrin-1: small Rho-GTPases, MAP-Kinases, second
      messengers and the Microtubule Associated Protein 1B (MAP1B).

PMID- 15960986
TI  - Tissue-engineering approaches for axonal guidance.
AB  - Owing to the profound impact of nervous system damage, extensive studies have
      been carried out aimed at facilitating axonal regeneration following injury.
      Tissue engineering, as an emerging and rapidly growing field, has received
      extensive attention for nervous system axonal guidance. Numerous engineered
      substrates containing oriented extracellular matrix molecules, cells or channels
      have displayed potential of supporting axonal regeneration and functional
      recovery. Most attempts are focused on seeking new biomaterials, new cell
      sources, as well as novel designs of tissue-engineered neuronal bridging devices,
      to generate safer and more efficacious neuronal tissue repairs.

PMID- 15960987
TI  - The role of mast cells in migraine pathophysiology.
AB  - Mast cells are critical players in allergic reactions, but they have also been
      shown to be important in immunity and recently also in inflammatory diseases,
      especially asthma. Migraines are episodic, typically unilateral, throbbing
      headaches that occur more frequently in patients with allergy and asthma implying
      involvement of meningeal and/or brain mast cells. These mast cells are located
      perivascularly, in close association with neurons especially in the dura, where
      they can be activated following trigeminal nerve, as well as cervical or
      sphenopalatine ganglion stimulation. Neuropeptides such as calcitonin gene
      related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate
      cyclase activating peptide (PACAP), and substance P (SP) activate mast cells
      leading to secretion of vasoactive, pro-inflammatory, and neurosensitizing
      mediators, thereby contributing to migraine pathogenesis. Brain mast cells can
      also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6
      (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to
      corticotropin-releasing hormone (CRH), a mediator of stress which is known to
      precipitate or exacerbate migraines. A better understanding of brain mast cell
      activation in migraines would be useful and could lead to several points of
      prophylactic intervention.

PMID- 15960984
TI  - Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's
      disease.
AB  - More than a century has elapsed since the description of Alois Alzheimer's
      patient Auguste D. Yet, the well-documented generation of beta-amyloid aggregates
      and neurofibrillary tangles that define Alzheimer's disease is believed to
      represent only a portion of the cellular processes that can determine the course
      of Alzheimer's disease. Understanding of the complex nature of this disorder has
      evolved with an increased appreciation for pathways that involve the generation
      of reactive oxygen species and oxidative stress, apoptotic injury that leads to
      nuclear degradation in both neuronal and vascular populations, and the early loss
      of cellular membrane asymmetry that mitigates inflammation and vascular
      occlusion. Recent work has identified novel pathways, such as the Wnt pathway and
      the serine-threonine kinase Akt, as central modulators that oversee cellular
      apoptosis and the formation of neurofibrillary tangles through their downstream
      substrates that include glycogen synthase kinase-3beta, Bad, and Bcl-xL. Other
      closely integrated pathways control microglial activation, release of
      inflammatory cytokines, and caspase and calpain activation for the processing of
      amyloid precursor protein, tau protein cleavage, and presenilin disposal. New
      therapeutic avenues that are just open to exploration, such as with nicotinamide
      adenine dinucleotide modulation, cell cycle modulation, metabotropic glutamate
      system modulation, and erythropoietin targeted expression, may provide both
      attractive and viable alternatives to treat Alzheimer's disease.

PMID- 15960989
TI  - Smoking, health, risk, and perception.
AB  - We provide a description of health-related incentives faced by a rational smoker
      by considering the role of perception in both immediate quality-of-life effects
      of smoking and future risk of mortality. A person who adapts psychologically to a
      lowered health state, smokes more early in life and shifts demands for health
      investments and health-complementary activities later in life. He also smokes
      more in total. Someone aware of the full mortality consequences of smoking,
      smokes less and demands less medical care than someone who believes that these
      effects are highly reversible. The impacts of new information on mortality risk
      are most valuable early in life. Lastly, someone endowed with a longer life
      expectancy smokes more in the first part of life but conditional on access to
      medical care.

PMID- 15960990
TI  - A nonparametric elicitation of the equity-efficiency trade-off in cost-utility
      analysis.
AB  - We performed an empirical elicitation of the equity-efficiency trade-off in cost
      utility analysis using the rank-dependent quality-adjusted life-year (QALY)
      model, a model that includes as special cases many of the social welfare
      functions that have been proposed in the literature. Our elicitation method
      corrects for utility curvature and, therefore, our estimated equity weights are
      not affected by diminishing marginal utility. We observed a preference for
      equality in the allocation of health. The data suggest that the elicited equity
      weights were jointly determined by preferences for equality and by insensitivity
      to group size. A procedure is proposed to correct the equity weights for
      insensitivity to group size. Finally, we give an illustration how our method can
      be implemented in health policy.

PMID- 15960991
TI  - Axioms for health care resource allocation.
AB  - This paper examines principles of health care resource allocation based on axioms
      for individual preferences and distributive justice. We establish axioms for
      representing individual preferences by quality-adjusted life years (QALYs), as
      well as axioms for existence of a social welfare function depending only on
      QALYs. A symmetric Cobb-Douglas social welfare function is characterized by an
      axiom stating that social welfare is anonymous with respect to the distribution
      of individual life years. Replacing this axiom with an axiom of non-age
      dependence, we obtain a characterization of a utilitarian social welfare function
      with certain weights. Further, we give axioms for a social welfare function being
      a weighted sum of power transformations of individual QALYs.

PMID- 15960992
TI  - Health priorities and public preferences: the relative importance of past health
      experience and future health prospects.
AB  - We explore people's choices where the preference for those with worse future
      health prospects and the preference for the young over the old conflict. The
      empirical study used scenarios with four attributes: past years, past health,
      future years without treatment, and future health without treatment. One hundred
      respondents ranked various patient groups described in these terms. The results
      suggest a strong effect of past years: younger groups (40-year-olds) were always
      chosen over older ones (60-year-olds). Past health was significant in one
      question but not the other and future health and years without treatment were
      both non-significant.

PMID- 15960993
TI  - Does prevention save costs? Considering deferral of the expensive last year of
      life.
AB  - Published cost-effectiveness analyses may overstate the cost-effectiveness ratio
      of preventive care if they do not explicitly model the costs of the last year of
      life, which is postponed by prevention. To determine the degree of
      overestimation, the authors built a statistical model using Medicare expenditure
      data on survivors and decedents. The model shows that the cost-effectiveness
      ratio of prevention may decrease by up to US$ 11,000 per quality-adjusted life
      year saved when expenditure data on the last year life are used. The model is
      able to explain more than half of the median cost increase of published cost
      effectiveness analyses on clinical preventive services.

PMID- 15960994
TI  - State health insurance market reforms and access to insurance for high-risk
      employees.
AB  - A specific focus for state regulations of the small group insurance market was to
      increase offers and stabilize premiums for firms with high-risk workers. We
      examine the effect of reforms implemented from 1993 through 1996 on the
      likelihood of employer sponsored insurance coverage. We find that packages of
      reforms that included both guaranteed issue of some products and some form of
      rate variance restriction had significant positive effects (4.5 percentage
      points) on ESI coverage for high-risk compared with low-risk workers within small
      firms and a small negative effect (-1.7 percentage points) on low-risk workers in
      small compared with large firms. The mechanism for these effects was an increase
      in take-up, rather than offer. Reform packages that included both guaranteed
      issue of all products and rate variance restrictions had similar effects overall,
      although they did not meet criteria for significance. These effects seemed to act
      through increased offer rather than take-up.

PMID- 15960988
TI  - The role of central dopamine D3 receptors in drug addiction: a review of
      pharmacological evidence.
AB  - The cDNA for the dopamine D3 receptor was isolated and characterized in 1990.
      Subsequent studies have indicated that D3 receptors, as well as D3 receptor mRNA,
      are primarily localized in limbic regions in mammals. This finding led to the
      postulate that D3 receptors may be involved in drug dependence and addiction.
      However, this hypothesis has been difficult to test due to the lack of compounds
      with high selectivity for central D3 receptors. The interpretation of results
      from studies using mixed D2/D3 agonists and/or antagonists is problematic because
      these agents have low selectivity for D3 over D2 receptors and it is likely that
      their actions are primarily related to D2 receptor antagonism and possibly
      interaction with other neurotransmitter receptors. Currently, with the synthesis
      and characterization of new highly selective D3 receptor antagonists such as SB
      277011-A this difficulty has been surmounted. The purpose of the present article
      is to review, for the first time, the effects of various putative D3 receptor
      selective compounds in animal models of drug dependence and addiction. The
      results obtained with highly selective D3 receptor antagonists such as SB-277011
      A, SB-414796, and NGB-2904 indicate that central D3 receptors may play an
      important role in drug-induced reward, drug-taking, and cue-, drug-, and stress
      induced reinstatement of drug-seeking behavior. Provided these results can be
      extrapolated to human drug addicts, they suggest that selective DA D3 receptor
      antagonists may prove effective as potential pharmacotherapeutic agents to manage
      drug dependence and addiction.

PMID- 15960995
TI  - Implications of spillover effects within the family for medical cost
      effectiveness analysis.
AB  - Medical cost-effectiveness analyses traditionally treat patients as isolated
      individuals and neglect the effects of improvement in patients' health on the
      welfare of their family members. We use a model based on a family utility
      function with altruistic linkages to show that there can be direct and indirect
      effects on the welfare of all family members. We focus specially on a model of
      how the spillover effects to the spouse in a two-person family might affect
      choice of treatments for prostate cancer. We then test the predictions of this
      model by analyzing treatment choices of prostate cancer patients using the linked
      SEER-Medicare database. We find that our results are consistent with the model's
      predictions. We conclude that cost-effectiveness analyses may better reflect the
      full costs and benefits of medical interventions if they incorporate these family
      effects. However, concerns about equity present a dilemma for the practice of CEA
      from the societal perspective.

PMID- 15960996
TI  - Does provider variation matter to health plans?
AB  - Variance in treatments prescribed by an individual provider may indicate higher
      quality through better matching of patients to treatments or it may indicate
      uncertainty about the healthcare production function. It is unknown how health
      plans respond to provider-level treatment variation. We use a model drawn from
      the portfolio selection literature, which examines the choice among risky assets,
      or in this case, providers with heterogeneous treatment variance. We test this
      model on data from a behavioral healthcare vendor that exercises some control
      over provider selection. We find little evidence that the plan responds to
      provider-level variance.

PMID- 15960997
TI  - The significance of agricultural vs. natural ecosystem pathways in temperate
      climates in assessments of long-term radiological impact.
AB  - Recent developments in performance assessment biosphere models have begun to
      emphasise the importance of natural accumulation pathways. In contrast to the
      agricultural pathways, the database for natural ecosystem pathways is less well
      developed, leading to a mismatch in quality of representations of the two types
      of system. At issue is the lack of reliable soil-plant and animal ingestion
      transfer factors for key radionuclides in natural ecosystems. The relative
      importance of the agricultural vs. natural ecosystem pathways is investigated
      here, in the context of a temperate site in present day, Eastern France. The
      BIOMASS Candidate Critical Group (CCG) methodology has been applied to map a set
      of eight candidate critical groups derived from the present-day societal context
      onto physical locations within a simple model of a river catchment system. The
      overall assessment model has been implemented using the Aquabios code. Annual
      individual dose to each of the CCGs has been calculated for each of the key
      radionuclides (79Se, 94Nb, 99Tc, 129I, 135Cs and 237Np) released to the valley
      aquifer and river. In addition to the traditional agricultural pathways,
      lifestyle groups exploiting natural habitats are explicitly addressed. Results
      show the susceptibility of different candidate critical groups to different
      radionuclides. A reference database typical of those employed in long-term
      performance assessment models is employed. Doses from external exposure (94Nb)
      and dust inhalation (237Np) are shown to dominate agricultural food consumption
      by factors of more than six, but, with the reference data set, foodstuffs
      obtained from natural ecosystems do not contribute significantly to critical
      group dose and, at most, show similar exposures to the agricultural pathways.
      This may lead to the conclusion that natural food can be ruled out of
      consideration in performance assessment models. However, systematic parametric
      sensitivity studies carried out on soil-plant and animal ingestion transfer
      factors restrict the validity of this observation and demonstrate the limitations
      of existing databases. Remaining uncertainties can be reduced by improving
      structural models for performance assessment and by better characterisation of
      sources of locally obtained foods. Improved characterisation of radionuclide
      accumulation in natural ecosystems in temperate as well as alternative future
      climate states should complement the modelling approach.

PMID- 15960998
TI  - Radon and thoron progeny concentration variability in relation to meteorological
      conditions at Bucharest (Romania).
AB  - The paper presents results of natural radioactivity levels in the atmosphere
      obtained for a 5 years period (1994-1999) at the Bucharest Environmental
      Radioactivity Surveillance Station (BERSS). The variability of radon and thoron
      progeny activity concentrations is analysed in relation to the local dynamics of
      the meteorological parameters (wind speed, air temperature, air pressure, cloud
      cover, relative humidity). The radon and thoron progeny concentrations display a
      daily and seasonal variation, with the highest values in the early morning and
      the lowest values in the afternoon. The outdoor radon progeny concentrations show
      maximum values in autumn and minimum values in spring-summer. The outdoor thoron
      progeny concentrations display maximum values in autumn and minimum values in
      winter. Significant statistical correlations with the meteorological parameters
      were obtained. The study on the temporal variability of natural atmospheric
      radioactivity near Bucharest is a starting point for further assessment of the
      radiological consequences resulting from human activities.

PMID- 15960999
TI  - Patient attitudes toward emergency physician attire.
AB  - Previous studies have suggested that Emergency Department (ED) patient
      satisfaction is unaffected by physician attire. We conducted a before-and-after
      trial to test this hypothesis. A convenience sample of ED patients was surveyed
      during a 2-week period. In the first week, emergency physicians wore white coats
      and formal attire. In the second week, the same physicians wore scrubs. Patients
      were asked to indicate on a 100-mm visual analog scale (VAS) their ratings of
      physician appearance, satisfaction, and professionalism. The primary outcome was
      the difference in VAS scores between the two dress styles. There were 111
      patients surveyed. There were no significant differences between patients'
      evaluation of appearance (Delta=-.68 mm VAS, 95% confidence interval [CI] -5.5 to
      4.1), satisfaction (Delta=.83 mm VAS, 95% CI -3.0 to 4.6), or professionalism
      (Delta=-.46 mm VAS, 95% CI -3.6 to 2.6) between the two dress styles. Emergency
      physician attire does not affect patient satisfaction.

PMID- 15961000
TI  - Prevention of CS "tear gas" eye and skin effects and active decontamination with
      Diphoterine: preliminary studies in 5 French Gendarmes.
AB  - Ortho-chlorobenzylidene malononitrile (CS) "tear gas" is a lacrimating riot
      control agent causing eye irritation, excessive lacrimation, and blepharospasm.
      Diphoterine has been efficacious for decontamination of a wide variety of eye and
      skin chemical splashes and was tested in CS exposure. Five French Gendarmes
      either entered a standard training CS exposure chamber, developed eye or skin
      signs and symptoms, and were post-exposure decontaminated with Diphoterine or
      used Diphoterine as pre-CS exposure prophylaxis in the eyes and on the face
      before entering the chamber. Gendarmes who entered the CS chamber without prior
      application of Diphoterine developed expected effects of excessive lacrimation,
      eye irritation, and blepharospasm. After post-exposure Diphoterine
      decontamination, in four Gendarmes these effects rapidly resolved and they were
      fully operational. When Diphoterine was applied to the eyes and face before
      entering the CS chamber, the expected effects did not occur and the single
      Gendarme remained fully operational on exiting the chamber. These results suggest
      that Diphoterine can prevent or rapidly ameliorate the ocular and dermal effects
      of CS and allow law enforcement personnel to remain fully operational or rapidly
      regain operational status after decontamination.

PMID- 15961001
TI  - Is emergent anti-hypertensive treatment beneficial in intracranial hemorrhage?
AB  - A retrospective chart review of adult patients with primary intracranial
      hemorrhage (ICH) was conducted to determine the effects of emergent anti
      hypertensives on mortality. Data included mean arterial pressure (MAP), Glascow
      Coma Scale score (GCS), ICH size, and anti-hypertensive treatment. Multi-variable
      logistic regression determined the effect of anti-hypertensives on ICH mortality.
      Of 66 patients studied, the overall mortality was 30.3%. Mortality was 34.5% for
      patients initially treated with anti-hypertensives vs. 25.8% for patients not
      treated. After controlling for age, MAP, GCS, and ICH size, anti-hypertensives
      given within the first 6 h of presentation were associated with a reduction in
      mortality with a p value of 0.0375 and an odds ratio of 140 (95% confidence
      interval [CI] 1.332 to >999). However, this effect may not occur in patients
      presenting with a systolic blood pressure (SBP)<200 mm Hg. In conclusion, in
      patients with primary intracranial hemorrhage, there was a significant decrease
      in mortality associated with emergent anti-hypertensive therapy. A larger
      prospective study is needed to confirm these findings, define the subgroups that
      may benefit, and better determine the effect size.

PMID- 15961002
TI  - The fast is positive, now what? Derivation of a clinical decision rule to
      determine the need for therapeutic laparotomy in adults with blunt torso trauma
      and a positive trauma ultrasound.
AB  - INTRODUCTION: The object of this study was to derive a clinical decision rule for
      therapeutic laparotomy among adult blunt trauma patients with a positive
      abdominal ultrasound for trauma (FAST) examination. METHODS: We retrospectively
      reviewed the trauma registry and medical records of all critical trauma patients
      who underwent a FAST examination in the emergency department (ED) in a university
      Level I trauma center over a 3-year period. Blunt trauma patients aged >16 years
      who had a positive FAST examination (defined as the presence of intraperitoneal
      fluid) were eligible. We selected seven clinical and ultrasound variables
      available during ED resuscitation for analysis: age, presence of an episode of
      hypotension (systolic blood pressure <90 torr in the ED), presence of abdominal
      tenderness, chest injury, pelvic fracture, femur fracture, and FAST fluid
      location (right upper quadrant [RUQ] only; RUQ plus other location; other
      location only). The primary outcome variable was whether a laparotomy was
      performed and whether this laparotomy was needed to provide the definitive
      surgical intervention ("therapeutic laparotomy"). We analyzed the variables using
      binary recursive partitioning analysis to create a decision rule. RESULTS: There
      were 2336 FAST examinations performed during the study period, resulting in 230
      (9.8%) positive examinations in patients meeting inclusion criteria. There were
      135 patients who had therapeutic laparotomies and 95 who did not need laparotomy.
      The groups were similar in baseline characteristics. In the recursive
      partitioning analysis, the first node in the decision tree was the presence of
      fluid in the RUQ. Of the 144 patients with RUQ fluid, 105 (73%, 95% confidence
      interval [CI] 64%-80%) required therapeutic laparotomy. Of the 86 patients
      without RUQ fluid, 30 (35%, 95% CI 25%-46%) nevertheless required therapeutic
      laparotomies, and the variables blood pressure, femur fracture, abdominal
      tenderness, and age further divided these patient into high- and low-risk groups.
      Of the 12 patients without RUQ fluid who had normal blood pressures, no femur
      fractures, no abdominal tenderness, and were aged 60 years and younger, none (95%
      CI 0%-22%) required therapeutic laparotomy. In conclusion, given a positive FAST
      examination, the presence of fluid in the RUQ is an important predictor of the
      need for therapeutic laparotomy. CONCLUSION: In the absence of fluid in the RUQ,
      there are other clinical variables that may allow for the development of a
      clinical decision rule regarding the need for therapeutic laparotomy.

PMID- 15961003
TI  - Subarachnoid hemorrhage diagnosis by computed tomography and lumbar puncture: are
      fifth generation CT scanners better at identifying subarachnoid hemorrhage?
AB  - This study sought to determine the sensitivity and specificity of modern computed
      tomography (CT) scans for the diagnosis of subarachnoid hemorrhage (SAH). No
      studies have been done recently with fifth generation CT scanners to look at the
      diagnosis of SAH. A retrospective chart review was done of Emergency Department
      (ED), laboratory, and hospital records at Pitt County Memorial Hospital in
      Greenville, North Carolina over 1 year from January 1, 2002 to December 31, 2002.
      Patients presented with headache and had a CT scan of the head with a fifth
      generation multi-detector CT scanner followed by a lumbar puncture (LP) to rule
      out SAH. There were 177 patients who presented to the ED with headache and went
      on to have a CT scan and an LP to rule out SAH. No patients who had a negative CT
      were found to have a subarachoid hemorrhage. It is concluded that fifth
      generation CT scanners are probably more sensitive than earlier scanners at
      detecting SAH.

PMID- 15961004
TI  - Comparison of levalbuterol and racemic albuterol combined with ipratropium
      bromide in acute pediatric asthma: a randomized controlled trial.
AB  - Our study compared levalbuterol (LEV) to the combination of racemic albuterol
      (RAC) and ipratropium bromide (IB) in 140 patients aged 6-18 years presenting to
      a tertiary hospital Emergency Department with acute asthma and a peak expired
      flow rate (PEF)<80% predicted. Patients were randomized to: LEV (<or=6 nebs LEV
      1.25 mg); or RAC/IB (<or=3 nebs RAC 5.0 mg+IB 0.25 mg followed as needed by <or=3
      nebs RAC 5.0 mg). No difference was noted in the study population (mean age 11.6
      years and initial mean predicted PEF 49.5%) between LEV (n=72) and RAC/IB (n=68)
      for study outcomes except for measures of heart rate (HR). Median % HR increase
      for RAC/IB (26%) exceeded LEV (9%) (p<0.001). In a sample of children with acute
      asthma and initial mean PEF<50% predicted, LEV was associated with less
      tachycardia but had no other advantage over RAC combined with IB.

PMID- 15961005
TI  - Marked elevation of cerebrospinal fluid white blood cell count: an unusual case
      of Streptococcus pneumoniae meningitis, differential diagnosis, and a brief
      review of current epidemiology and treatment recommendations.
AB  - The diagnosis of bacterial meningitis is rarely a difficult diagnostic dilemma
      when a patient presents with fever, headache, neck stiffness, and altered mental
      status. Unfortunately for the practicing clinician, patients are rarely that
      straightforward. Patients who are elderly, very young, or immuno-compromised
      often present with subtle findings, making the correct diagnosis a challenge. In
      addition, patients being treated with antibiotics may be misleading in their
      clinical presentation, leading to a missed diagnosis of meningitis. Only when one
      considers the diagnosis or obtains a sample of cerebrospinal fluid is the correct
      diagnosis made. Although the clinical scenario may suggest meningitis, it is the
      cerebrospinal fluid white blood cell count that establishes the definitive
      diagnosis. Despite the advent of systemic antibiotics over 50 years ago,
      bacterial meningitis continues to cause considerable morbidity and mortality
      worldwide. The following case report details a woman diagnosed with Streptococcus
      pneumoniae meningitis with an extremely high cerebrospinal white blood cell
      count. Although this is typically thought to be caused by abscesses or
      malignancy, meningitis alone may cause such an elevation. In addition, a brief
      review of the current epidemiology and treatment regimens for meningitis is
      discussed.

PMID- 15961006
TI  - An uncommon presentation of acute angle closure glaucoma.
AB  - Acute angle closure glaucoma is an ocular emergency that is treatable with prompt
      and appropriate intervention. Recognition of this disease entity is sometimes
      difficult. We report a case of bilateral acute angle closure glaucoma in a 55
      year-old, otherwise healthy individual, and discuss the different ways the
      condition may present. The anatomic and pathophysiologic progression leading to
      an event of angle closure is discussed and treatment modalities available to the
      Emergency Physician are presented.

PMID- 15961007
TI  - Bilateral peritonsillar abscesses: not your usual sore throat.
AB  - We describe a rare case of a previously healthy 30-year-old man who presented to
      the Emergency Department (ED) with bilateral peritonsillar abscesses. The
      clinical presentation of fever, trismus and odynophagia was consistent with
      pertonsillar abscess (PTA), but the presence of symmetric tonsillar swelling and
      midline uvula confounded the diagnosis. The true incidence of bilateral
      peritonsillar abscesses is unknown, but the incidence of unsuspected
      contralateral peritonsillar abscess identified at tonsillectomy has been reported
      to be between 1.9% and 24%. The diagnosis of bilateral peritonsillar abscesses
      should be considered when the clinical presentation suggests the diagnosis of
      PTA, but the physical examination reveals bilateral swollen tonsils with a
      midline uvula.

PMID- 15961008
TI  - Red flag in the emergency department: fracture and primary failure of a
      prosthetic valve.
AB  - This case report concerns a patient with fracture and primary dysfunction of a
      prosthetic valve. A 40-year-old man presented to the Emergency Department with a
      chief complaint of breakthrough pleuritic back pain and shortness of breath. Past
      surgical history was significant only for an aortic valve replacement and mitral
      valve replacement performed 16 years prior. The transthoracic echocardiography
      raised suspicion of prosthesis malposition. The patient was taken to the
      operating room by cardiothoracic surgeons for valve replacement. Operative
      findings revealed that a prosthetic valve leaflet in the mitral position had
      broken off. Primary prosthetic valve failure should not be overlooked in the
      differential diagnosis of patients with valve replacement and a rapidly
      deteriorating clinical course. Emergency echocardiography is a guide to
      convenient diagnosis and management. Early surgical consultation and early
      reparative surgery might prevent unnecessary morbidity and mortality.

PMID- 15961009
TI  - Acute abdominal aortic aneurysm rupture presenting as transient paralysis of the
      lower legs: a case report.
AB  - This article describes the case of a 40-year-old man with transient paralysis of
      both legs as the major symptom of an acute abdominal aortic aneurysm rupture
      presumably due to the occlusion of blood flow to the conus medullaris.

PMID- 15961011
TI  - An abused five-month-old girl: Hangman's fracture or congenital arch defect?
AB  - Hangman's fractures are a rare finding in childhood. In case of suspected or
      proven child abuse, differentiation with a congenital defect of the posterior
      arch of C2 is essential. We present the case of a 5-month-old girl, who had a
      history of being physically abused by one of her caretakers. On the lateral view
      of the cervical spine, a defect of the posterior elements of C2 and an
      anterolisthesis of C2 on C3 was seen. CT scan showed a bilateral defect in the
      posterior elements of C2. No soft-tissue swelling of hematoma was noted. MRI
      showed a normal signal intensity of the intervertebral disc C2-C3. No haematoma
      was noted. Clinical examination revealed a slight head lag and local tenderness;
      there were no neurological deficits. This case shows that the differentiation
      between a congenital C2 arch defect and a hangman's fracture is precarious. In
      this case the findings on MRI and CT scan were interpreted as a congenital
      posterior arch defect (spondylolysis).

PMID- 15961010
TI  - Streptococcus viridans endocarditis from tongue piercing.
AB  - Body piercing and tattooing have undergone a revival in popularity. We present
      the case of a 27-year-old man with a recent tongue piercing and infective
      endocarditis of the aortic valve. He was treated with a 6-week course of
      intravenous antibiotics, but eventually required a Ross procedure for progressive
      aortic insufficiency.

PMID- 15961012
TI  - Major vascular injury after laparoscopic tubal ligation.
AB  - Laparoscopy has become an established approach with diverse applications in both
      diagnostic and therapeutic surgical procedures. In general, the procedure is safe
      and effective and offers the advantage of being less invasive than conventional
      surgery. Complications after laparoscopy are uncommon but among them major
      vascular injury is potentially the most fatal, with recognition or mortality
      typically occurring intra-operatively or in the immediate post-operative period.
      We report the case of a delayed emergency department presentation of a major
      vascular injury after an elective laparoscopic tubal ligation. The prevalence,
      diagnosis, pathophysiolgy and management of major vascular injury after
      laparoscopic surgery is discussed.

PMID- 15961013
TI  - Methadone-induced bradycardia.
AB  - Methadone is commonly used in opiate detoxification in high dose. It has a
      molecular structure similar to verapamil and has been reported to cause similar
      side effects with continuous high-dose infusion. We report the case of a patient
      with a history of addiction and abuse of alprazolam and hydrocodone who developed
      sinus bradycardia after being started on oral methadone for detoxification. The
      potential of methadone to cause side effects similar to verapamil must be
      considered in any patient taking methadone.

PMID- 15961015
TI  - Luxatio erecta: clinical presentation and management in the emergency department.
AB  - Luxatio erecta (inferior glenohumeral dislocation) is an uncommon type of
      shoulder dislocation. Early recognition and reduction is important to prevent
      neurovascular sequelae. We report two cases of luxatio erecta in order to
      describe the clinical presentation and reduction technique in the Emergency
      Department.

PMID- 15961014
TI  - Are one or two dangerous? Opioid exposure in toddlers.
AB  - Ingestions of opioid analgesics by children may lead to significant toxicity as a
      result of depression of the respiratory and central nervous systems. A review of
      the medical literature was performed to determine whether low doses of opioids
      are dangerous in the pediatric population under 6 years old. Methadone was found
      to be the most toxic of the opioids; doses as low as a single tablet can lead to
      death. All children who have ingested any amount of methadone need to be observed
      in an Emergency Department (ED) for at least 6 h and considered for hospital
      admission. Most other opioids are better tolerated in ingestions as small as one
      or two tablets. Based on the limited data available for these opioids, we
      conclude that equianalgesic doses of 5 mg/kg of codeine or greater require 4 to 6
      h of observation in the ED. Data for propoxyphene and all extended-release
      preparations are limited; their prolonged half-lives would suggest the need for
      longer observation periods. All opioid ingestions leading to respiratory
      depression or significant central nervous system depression require admission to
      an intensive care unit.

PMID- 15961016
TI  - Chest pain and arthritis.

PMID- 15961017
TI  - Cement burns.

PMID- 15961018
TI  - Rectus sheath hematoma after acupuncture.

PMID- 15961020
TI  - I work in the ER.

PMID- 15961021
TI  - Upper airway mass mimicking near-fatal asthma.

PMID- 15961022
TI  - Lateral chest radiographs for detecting pneumothorax in supine trauma patients.

PMID- 15961023
TI  - Workforce projections for emergency medicine in Puerto Rico: a five-year follow
      up of an evident demand.
AB  - In this study, two mathematical equations were used to calculate and establish
      the actual Emergency Medicine workforce needed in Puerto Rico (PR) and project
      the time frame to meet the actual demand. 1) Supply equals the number of existing
      Emergency Physicians (EPs) plus residency-trained graduates in EM per year minus
      the annual attrition rate (3%); and 2) Demand equals six (6) full time equivalent
      positions per Emergency Department (ED) times the total number of EDs in PR.
      Under both scenarios tested, the significant EP shortage in PR will continue
      until 2044. The actual calculated shortage is 287 EPs. There is an actual
      significant shortage in the Puerto Rico EP workforce. It will take a long time to
      make leaders understand the positive impact of having residency-trained EPs in
      every ED, on quality patient care and the whole health care system.

PMID- 15961024
TI  - Biodefense research: an emerging conundrum.
AB  - Biodefense research creates a conundrum for the scientific community--what are
      the permissible limits of biodefense research and how can knowledge in the life
      sciences be protected against misuse? As biodefense research expands to counter
      the threat of bioterrorism, so does suspicion and the need for guidance to
      respond to these concerns.

PMID- 15961025
TI  - Natural attenuation and enhanced bioremediation of organic contaminants in
      groundwater.
AB  - An area of intense scientific and practical interest is the biogeochemical and
      microbial processes determining the success of natural attenuation,
      biostimulation and/or bioaugmentation treatments for organic contaminants in
      groundwater. Recent studies in this area have focused on the reductive
      dechlorination of chlorinated solvents, the degradation of the fuel additive
      methyl tert-butyl ether, and the removal of long-term hydrocarbon contamination.
      These studies have been facilitated by the use of stable isotope analysis to
      demonstrate in situ bioremediation and push-pull tests, in which isotopes are
      injected into aquifers and then quickly retrieved and analyzed, to measure in
      situ activity. Molecular tools such as quantitative PCR, the detection of mRNA
      expression, and numerous DNA fingerprinting methods have also proved valuable,
      being employed to identify and sometimes quantify environmentally important
      organisms or changes in communities. Methods to track bacteria and tools to
      characterize bacterial attachment properties have also offered insight into
      bacterial transport in situ.

PMID- 15961026
TI  - Monitoring of microbial metal transformations in the environment.
AB  - The biotransformation of metals is an exciting, developing strategy to treat
      metal contamination, especially in environments that are not accessible to other
      remediation technologies. However, our ability to benefit from these strategies
      hinges on our ability to monitor these transformations in the environment. This
      involves monitoring metals in both solid and aqueous samples, distinguishing
      between different chemical states, and obtaining information on the activities of
      specific microbial taxa in communities that inhabit the treated site.
      Accomplishing these goals requires cooperation among scientists from various
      disciplines and would benefit from both new, innovative approaches and the
      tailoring of established methods to control metal mobility in the environment.

PMID- 15961027
TI  - Genome-assisted analysis of dissimilatory metal-reducing bacteria.
AB  - The availability of whole genome sequences for Shewanella oneidensis and
      Geobacter sulfurreducens has provided numerous new biological insights into the
      function of these model dissimilatory metal-reducing bacteria. Many of these
      findings, including the identification of a high number of c-type cytochromes in
      both organisms, have resulted from comparative genomic analyses, and several have
      been experimentally confirmed. These genome sequences have also aided the
      identification of genes important for the reduction of metal ions and other
      electron acceptors utilized during anaerobic growth, by facilitating the
      identification of genes disrupted by random insertions. Technologies for assaying
      global expression patterns for genes and proteins have also been employed, but
      their application has been limited mainly to the analysis of the role of global
      regulatory genes and to identifying genes expressed or repressed in response to
      specific electron acceptors. It is anticipated that details of the mechanisms of
      metal ion respiration, and metabolism in general, will eventually be revealed by
      comprehensive, systems-level analyses enabled by functional genomics data.

PMID- 15961028
TI  - Bioremediation of polynitrated aromatic compounds: plants and microbes put up a
      fight.
AB  - Industrialization and the quest for a more comfortable lifestyle have led to
      increasing amounts of pollution in the environment. To address this problem,
      several biotechnological applications aimed at removing this pollution have been
      investigated. Among these pollutants are xenobiotic compounds such as
      polynitroaromatic compounds--recalcitrant chemicals that are degraded slowly.
      Whereas 2,4,6-trinitrophenol (TNP) can be mineralized and converted into carbon
      dioxide, nitrite and water, 2,4,6-trinitrotoluene (TNT) is more recalcitrant-
      although several microbes can use it as a nitrogen source. The most effective in
      situ biotreatments for TNT are the use of bioslurry (which can be preceded by an
      abiotic step) and phytoremediation. Phytoremediation can be enhanced by using
      transgenic plants alone or together with microbes.

PMID- 15961029
TI  - Biodegradation and Rhodococcus--masters of catabolic versatility.
AB  - The genus Rhodococcus is a very diverse group of bacteria that possesses the
      ability to degrade a large number of organic compounds, including some of the
      most difficult compounds with regard to recalcitrance and toxicity. They achieve
      this through their capacity to acquire a remarkable range of diverse catabolic
      genes and their robust cellular physiology. Rhodococcus appear to have adopted a
      strategy of hyper-recombination associated with a large genome. Notably, they
      harbour large linear plasmids that contribute to their catabolic diversity by
      acting as 'mass storage' for a large number of catabolic genes. In addition,
      there is increasing evidence that multiple pathways and gene homologues are
      present that further increase the catabolic versatility and efficiency of
      Rhodococcus.

PMID- 15961030
TI  - The evolution of IncP catabolic plasmids.
AB  - The recent adoption of whole plasmid genome sequencing as a routine analytical
      technique has provided the basis for cataloging the historical events through
      which plasmids are assembled from the available families of modular plasmid
      components. Horizontal gene transfer mediated by plasmids plays an important role
      in the adaptation of bacteria to the presence of specific metabolizable
      compounds, including man-made chemicals, in the surrounding environment.
      Bacterial plasmid genome sequence comparisons indicate that plasmids have complex
      genetic histories resulting from transposition, homologous recombination, and
      illegitimate recombinational events. Evidence from IncP plasmid genome sequences
      indicates that cryptic plasmid backbones acquire diverse catabolic pathways
      through gene capture and horizontal gene transfer.

PMID- 15961031
TI  - Marine phage genomics: what have we learned?
AB  - Marine phages are the most abundant and diverse form of life on the planet, and
      their genomes have been described as the largest untapped reservoir of genomic
      information. To date, however, the complete genome sequences of only 17 marine
      phage are known. Nevertheless, these genomes have revealed some interesting
      features, including the presence of photosynthetic genes in cyanophage and common
      patterns of genomic organization. Intriguing findings are also being made from
      studies of the uncultivated marine viral community genome ('metavirome'). The
      greatest challenge in interpreting the biology of these phages, and for making
      comparisons with their terrestrial counterparts, is the high proportion of
      unidentifiable open reading frames (approximately 60%). Future studies are likely
      to focus on sequencing more marine phage genomes from disparate hosts and diverse
      environments and on further basic studies of the biology of existing marine
      phages.

PMID- 15961032
TI  - Expanding the alkane oxygenase toolbox: new enzymes and applications.
AB  - As highly reduced hydrocarbons are abundant in the environment, enzymes that
      catalyze the terminal or subterminal oxygenation of alkanes are relatively easy
      to find. A number of these enzymes have been biochemically characterized in
      detail, because the potential of alkane hydroxylases to catalyze high added-value
      reactions is widely recognized. Nevertheless, the industrial application of these
      enzymes is restricted owing to the complex biochemistry, challenging process
      requirements, and the limited number of cloned and expressed enzymes. Rational
      and evolutionary engineering approaches have started to yield more robust and
      versatile enzyme systems, broadening the alkane oxygenase portfolio. In addition,
      metagenomic approaches provide access to many novel alkane oxygenase sequences.

PMID- 15961033
TI  - Laboratory evolution of catabolic enzymes and pathways.
AB  - The laboratory evolution of environmentally relevant enzymes and proteins has
      resulted in the generation of optimized and stabilized enzymes, as well as
      enzymes with activity against new substrates. Numerous methods, including random
      mutagenesis, site-directed mutagenesis and DNA shuffling, have been widely used
      to generate variants of existing enzymes. These evolved catabolic enzymes have
      application for improving biodegradation pathways, generating engineered pathways
      for the degradation of particularly recalcitrant compounds, and for the
      development of biocatalytic processes to produce useful compounds. Regulatory
      proteins associated with catabolic pathways have been utilized to generate
      biosensors for the detection of bioavailable concentrations of environmentally
      relevant chemicals.

PMID- 15961034
TI  - Tunable promoters in systems biology.
AB  - The construction of synthetic promoter libraries has represented a major
      breakthrough in systems biology, enabling the subtle tuning of enzyme activities.
      A number of tools are now available that allow the modulation of gene expression
      and the detection of changes in expression patterns. But, how does one choose the
      correct promoter and what are the appropriate methods for reading promoter
      strength? Furthermore, how fine should the tuning of gene expression be for some
      specific applications and how can the simultaneous and individual tuning of
      multiple genes be achieved? Some recent studies have helped us to find answers to
      many of these questions.

PMID- 15961035
TI  - All systems go: launching cell simulation fueled by integrated experimental
      biology data.
AB  - Biological simulation serves to unify the basic elements of systems biology,
      namely, model selection, experimentation and model refinement. To select
      biochemical models for simulation, metabolome analysis can be performed using
      capillary electrophoresis or liquid chromatography coupled with mass
      spectrometry. In this manner, selected models can be elaborated with
      temporal/spatial gene and protein expression data obtained from model organisms
      such as Escherichia coli. The E. coli single gene deletion mutant library (KO
      collection) and His-tag/GFP-fusion single open reading frame clone expression
      library (ASKA) are powerful resources for this task. The integration of parallel
      experimental datasets into dynamic simulation tools forms the remaining challenge
      for the systematic analysis and elucidation of biological networks and holds
      promise for biotechnological applications.

PMID- 15961036
TI  - From genomes to in silico cells via metabolic networks.
AB  - Genome-scale metabolic models are the focal point of systems biology as they
      allow the collection of various data types in a form suitable for mathematical
      analysis. High-quality metabolic networks and metabolic networks with
      incorporated regulation have been successfully used for the analysis of
      phenotypes from phenotypic arrays and in gene-deletion studies. They have also
      been used for gene expression analysis guided by metabolic network structure,
      leading to the identification of commonly regulated genes. Thus, genome-scale
      metabolic modeling currently stands out as one of the most promising approaches
      to obtain an in silico prediction of cellular function based on the interaction
      of all of the cellular components.

PMID- 15961037
TI  - The Yeast Systems Biology Network: mating communities.
AB  - Systems biology requires model organisms that allow detailed studies to be
      performed rapidly, accurately and reproducibly. Such model systems are important
      driving forces for elucidating the principle properties of biomolecules, for
      developing general concepts for the quantitative description of living cells, and
      for generating the computational tools for systems analyses. The yeast
      Saccharomyces cerevisiae serves as an excellent model system. To coordinate
      efforts and to bring the yeast research and systems biology communities together,
      the Yeast Systems Biology Network has recently been started.

PMID- 15961038
TI  - Strain improvement by metabolic engineering: lysine production as a case study
      for systems biology.
AB  - A central goal of systems biology is the elucidation of cell function and
      physiology through the integrated use of broad based genomic and physiological
      data. Such systemic approaches have been employed extensively in the past, as
      they are a central element of metabolic flux analysis, the distribution of
      kinetic control in pathways, and the key differentiating characteristic of
      metabolic engineering. In one case study, these tools have been applied to the
      improvement of lysine-producing strains of Corynebacterium glutamicum. The
      systematic study of the physiology of this organism allowed the identification of
      specific metabolic targets and subsequently led to significant improvements in
      product yield and productivity. This case study can serve as a guide for the
      development of systems biology tools for the utilization of large volumes of cell
      and genome-wide transcriptional and physiological data.

PMID- 15961039
TI  - Neuronal proteins custom designed by alternative splicing.
AB  - The evolution of alternative splicing in eukaryotes greatly expanded the number
      of functionally distinct proteins that could be produced from a finite gene pool.
      Extensive in the brains of higher organisms, alternative splicing might be the
      primary mechanism for generating the spectrum of protein activities that support
      complex brain functions. Alternative splicing is controlled at the level of
      individual neurons to custom design proteins for optimal performance. The
      expression profiles of splice isoforms are modified during development and as
      neuronal activity changes. Alternative splicing can lead to incremental, long
      lasting changes in ion channel and receptor activities, independent of changes in
      gene transcription. Recent studies of tissue-specific splicing factors are
      revealing how coordinated alterations in alternative splicing of RNA transcripts
      control synaptic function.

PMID- 15961040
TI  - Trafficking of potassium channels.
AB  - Recent progress in our understanding of the trafficking of potassium channels can
      be seen in particular when considering the Kv-type channels. To date, we have
      discovered that folding of the Kv1.3 T1 domain begins in the ribosomal exit
      tunnel, and that the cell surface expression of Kv4 channels is enhanced by the
      presence of two recently identified accessory subunits. Current advances are
      beginning to enable us to understand the Kv supermolecular complex containing
      these subunits in crystallographic detail. In addition, determinants that govern
      the dendritic or axonal targeting of Kv channels have also been identified. In
      terms of the bigger picture, the careful analysis of gene expression patterns in
      the brain paves the way for studying trafficking in a physiological context.
      Indeed, neuronal activity has recently been shown to fine-tune the localization
      of Kv2.1 channels in microdomains of the neuronal plasma membrane.

PMID- 15961041
TI  - Accelerated and amplified neural responses in visual discrimination: Two features
      are processed faster than one.
AB  - Psychological and neurophysiological models of visual processing have
      traditionally emphasized hierarchical models to explain how separate features of
      visual stimuli are combined. This concept has been challenged recently with the
      demonstration of simultaneous activation of multiple visual areas and rapid
      feedback to primary cortices. Here, we show human visual processing may involve
      similar mechanisms. Subjects discriminated targets from nontargets as a function
      of shape, color, or the conjunction of these features while event-related brain
      potentials (ERPs) were recorded. ERP components from 100 to 200 ms across
      posterior occipital-temporal cortices were fastest and largest for conjunction
      targets. These enhanced early responses were followed by task-specific sustained
      posterior activity (300-500 ms). Faster reaction times were correlated with
      enhanced and faster early processing in the visual ventral areas. These data
      demonstrate the human visual system conjoins features rapidly, accelerating and
      amplifying the processing of relevant stimulus dimensions.

PMID- 15961042
TI  - The fast optical signal--robust or elusive when non-invasively measured in the
      human adult?
AB  - Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral
      cortical tissue elicited by functional stimulation. For some 10 years, another
      optical signal has been reported to be accessible by NIRS. This signal has been
      reported to correlate to the electrophysiological response rendering NIRS an
      exquisite non-invasive approach to investigate neurovascular coupling in the
      human adult. Due to their typical latency of up to hundreds of milliseconds,
      these signals have been termed "fast" optical signals and have been postulated to
      stem from scatter changes in neuronal tissue, as a fingerprint of the
      electrophysiological response. Here, we utter a less optimistic view on the non
      invasive detectability of these changes in the human, motivated by an upper limit
      signal size estimation, predicting a signal size by orders of magnitude smaller
      than those previously reported. Also, we discuss the influence of small stimulus
      correlated movement artifacts potentially mimicking a fast optical signal. Based
      on invasive studies, we perform an upper limit estimation for changes in
      intensity and mean time of flight, which can be expected assuming a scatter
      change in the cerebral cortex while measuring on the surface of the head of an
      adult subject. Since the resulting numbers are far below those previously
      reported, we constructed a simple system, which minimizes technical noise. The
      system allows us to detect rather small intensity changes (2 x 10(-3)%) when
      averaging over approximately 3000 stimuli. Despite this outstandingly low noise
      level of the system, we find a reliable change in response to a sub-motor
      threshold steady state median nerve stimulation in just one single subject (8
      subjects examined, 4 subjects twice). Exceeding the motor threshold leads to
      large stimulus related artifacts, on a similar time scale and with comparable
      amplitude as previously reported signals. To check for potential modality
      specific problems, we next performed a visual stimulation study, avoiding
      potential motor artifacts. For the steady state visually evoked response, no
      subject yielded a reliable result (11 subjects examined, 4 subjects twice). The
      paper discusses these findings by a review of the literature on fast optical
      signals and their being accessible in the adult human.

PMID- 15961043
TI  - Target consolidation under high temporal processing demands as revealed by MEG.
AB  - We investigated the nature of resource limitations during visual target
      processing by imposing high temporal processing demands on the cognitive system.
      This was achieved by embedding target stimuli into rapid-serial-visual
      presentation-streams (RSVP). In RSVP streams, it is difficult to report the
      second of two targets (T2) if the second follows the first (T1) within 500 ms.
      This effect is known as the attentional blink (AB). For the AB to occur, it is
      essential that T1 is followed by a mask, as without such a stimulus, the AB is
      significantly attenuated. Usually, it is thought that T1 processing is delayed by
      the mask, which in turn delays T2 processing, increasing the likelihood for T2
      failures (AB). Predictions regarding amplitudes and latencies of cortical
      responses (M300, the magnetic counterpart to the P300) to targets were tested by
      investigating the neurophysiological effects of the post-T1 item (mask) by means
      of magnetoencephalography (MEG). Cortical M300 responses to targets drawn from
      prefrontal sources--areas associated with working memory--revealed accelerated T1
      yet delayed T2 processing with an intervening mask. The explanation we are
      proposing assumes that "protection" of ongoing T1 processing necessitated by the
      occurrence of the mask suppresses other activation patterns, which boosts T1 yet
      also hinders further processing. Our data shed light on the mechanisms employed
      by the human brain for ensuring visual target processing under high temporal
      processing demands, which is hypothesized to occur at the expense of subsequently
      presented information.

PMID- 15961044
TI  - Mapping postnatal mouse brain development with diffusion tensor microimaging.
AB  - While mouse brain development has been extensively studied using histology,
      quantitative characterization of morphological changes is still a challenging
      task. This paper presents how developing brain structures can be quantitatively
      characterized with magnetic resonance diffusion tensor microimaging coupled with
      techniques of computational anatomy. High resolution diffusion tensor images of
      ex vivo postnatal mouse brains provide excellent contrasts to reveal the
      evolutions of mouse forebrain structures. Using anatomical landmarks defined on
      diffusion tensor images, tissue level growth patterns of mouse brains were
      quantified. The results demonstrate the use of these techniques to three
      dimensionally and quantitatively characterize brain growth.

PMID- 15961045
TI  - Structural brain correlates of prepulse inhibition of the acoustic startle
      response in healthy humans.
AB  - Neural regions modulating prepulse inhibition (PPI) of the startle response, an
      operational measure of sensorimotor gating, are well established from animal
      studies using surgical and pharmacological procedures. The limbic and cortico
      pallido-striato-thalamic circuitry is thought to be responsible for modulation of
      PPI in the rat. The involvement of this circuitry in human PPI is suggested by
      observations of deficient PPI in a number of neuropsychiatric disorders
      characterized by abnormalities at some level in this circuitry and recent
      functional neuroimaging studies in humans. The current study sought to
      investigate structural neural correlates of PPI in a sample of twenty-four right
      handed, healthy subjects (10 men, 14 women). Subjects underwent magnetic
      resonance imaging (MRI) at 1.5 T and were assessed (off-line) on acoustic PPI
      using electromyographic recordings of the orbicularis oculi muscle beneath the
      right eye. Optimized volumetric voxel-based morphometry (VBM) implemented in
      SPM99 was used to investigate the relationship of PPI (prepulse onset-to-pulse
      onset interval 120 ms) to regional grey matter volumes, covarying for sex.
      Significant positive correlations were obtained between PPI and grey matter
      volume in the hippocampus extending to parahippocampal gyrus, basal ganglia
      including parts of putamen, globus pallidus, and nucleus accumbens, superior
      temporal gyrus, thalamus, and inferior frontal gyrus. These findings identify the
      relationship between PPI and grey matter availability on a highly spatially
      localized scale in brain regions shown to be activated in recent functional
      neuroimaging studies in association with PPI in healthy humans and demonstrate
      the validity of structural neuroimaging methods in delineating the neural
      mechanisms underlying human PPI.

PMID- 15961046
TI  - The relationship between whole brain volume and disability in multiple sclerosis:
      a comparison of normalized gray vs. white matter with misclassification
      correction.
AB  - We used SPM99 to obtain normalized whole brain volumes of gray matter, white
      matter, and total parenchyma in patients with multiple sclerosis (MS) (n = 41)
      and age-/sex-matched normal controls (n = 18). As SPM99's automated gray/white
      matter volumes were significantly influenced by tissue compartment
      misclassification due to the effect of MS-related brain lesions, we corrected
      these automated volumes for misclassification before performing our primary
      analyses. For MS patients (disease duration = 9.5 +/- 6.3 years; EDSS score = 3.2
      +/- 1.8; 25FTW = 6.6 +/- 3.1 s), we also measured lesion load (total T1
      hypointense [T1LV] and FLAIR hyperintense lesion volume [FLLV]), central brain
      atrophy (third ventricular width [TVW] and bicaudate ratio [BCR]), and clinical
      status (Expanded Disability Status Scale [EDSS] and 25-ft timed walk [25FTW]).
      Patients with MS had lower gray matter (707 +/- 33 cm(3) [-3.9%], P = 0.003) and
      total parenchymal volume (1088 +/- 48 cm(3) [-3.8%], P = 0.003), but only a trend
      for lower white matter volume (381 +/- 25 cm(3) [-3.7%], P = 0.052) relative to
      normal controls (gray matter: 736 +/- 33 cm(3); total parenchyma: 1132 +/- 49
      cm(3); white matter: 396 +/- 26 cm(3)). Gray matter atrophy was related to
      clinical status (EDSS, 25FTW, and disease duration), lesion load (T1LV and FLLV),
      and central brain atrophy (TVW and BCR), whereas white matter atrophy was related
      to only central brain atrophy. These findings suggest that gray matter loss is
      related to other aspects of brain pathology and has more clinical relevance than
      white matter atrophy in MS.

PMID- 15961047
TI  - Delayed rather than decreased BOLD response as a marker for early Alzheimer's
      disease.
AB  - Functional MRI (fMRI) in established Alzheimer's disease (AD) shows regionally
      altered blood oxygenation level dependent (BOLD) responses. Mild cognitive
      impairment (MCI) is thought to represent an intermediate state between health and
      early Alzheimer's disease. To study this probable early dementia stage pathology,
      we studied in detail the BOLD response in MCI during visual encoding. 28 MCI
      patients, 18 AD patients, and 41 healthy elderly controls performed a face
      encoding task during fMRI scanning. Data were analyzed using orthogonal
      regressors, each representing different phases of the BOLD response (from slow to
      fast). Using a mixed effects model, regressor x group interactions were analyzed
      applying P < 0.05, corrected. In occipital regions, MCI patients could be
      distinguished significantly better from controls and AD patients with a regressor
      of the early phase of the (fast) BOLD response than with the regressor of the
      late (slow) BOLD phase. Occipitally, the early phase BOLD response was
      significantly diminished in MCI patients compared to controls, and significantly
      increased when compared to AD. AD patients showed diminished early phase
      activation in widespread regions throughout the brain when compared to controls.
      There were no differences in the late (slow) phase of the BOLD response. This
      study stresses the importance of analyzing early phase BOLD responses and not
      only using one model of the BOLD response in neurodegenerative diseases. The
      increasing delay of the BOLD response from controls to MCI to AD may be
      consistent with the idea that MCI is a transitional state between healthy aging
      and dementia. Analyzing differences in different phases of the BOLD response
      introduces new opportunities to understand changes in regional brain dynamics in
      MCI and how well this may serve as an early marker of AD pathology.

PMID- 15961048
TI  - Dynamics of male sexual arousal: distinct components of brain activation revealed
      by fMRI.
AB  - The peripheral mechanisms of male sexual arousal are well known. Recently,
      neuroimaging techniques, such as PET or fMRI, allowed the investigation of the
      subjacent cerebral mechanisms. In ten healthy subjects, we have simultaneously
      recorded fMRI images of brain activation elicited by viewing erotic scenes, and
      the time course of penile tumescence by means of a custom-built MRI-compatible
      pneumatic cuff. We have compared activation elicited by video clips with a long
      duration, that led to sexual arousal and penile erection, and activation elicited
      by briefly presented still images, that did induce sexual arousal without
      erection. This comparison and the use of the time course of penile tumescence in
      video clips allowed to perform a time resolved data analysis and to correlate
      different patterns of brain activation with different phases of sexual response.
      The activation maps highlighted a complex neural circuit involved in sexual
      arousal. Of this circuit, only a few areas (anterior cingulate, insula, amygdala,
      hypothalamus, and secondary somatosensory cortices) were specifically correlated
      with penile erection. Finally, these areas showed distinct dynamic relationships
      with the time course of sexual response. These differences might correspond to
      different roles in the development and appraisal of the sexual response. These
      findings shed light on the psychophysiology of male sexuality and open new
      perspectives for the diagnosis, therapy, and possible rehabilitation of sexual
      dysfunction.

PMID- 15961049
TI  - Familiarity enhances invariance of face representations in human ventral visual
      cortex: fMRI evidence.
AB  - Face recognition across different viewing conditions is strongly improved by
      familiarity. In the present study, we tested the hypothesis that the neural basis
      of this effect is a less view-dependent representation of familiar faces in
      ventral visual cortex by assessing priming-related fMRI repetition effects. 15
      healthy volunteers made male/female judgements on familiar (famous) and
      unfamiliar (novel) faces preceded by the same image, a different image of the
      same face, or another (unprimed) face. Reaction times revealed priming by same
      and different images independent of familiarity and more pronounced for same than
      different images. In the imaging data, a main effect of prime condition was found
      in bilateral fusiform and orbitofrontal regions. A right anterior fusiform region
      expressed stronger response decreases to repetition of familiar than unfamiliar
      faces. Bilateral mid-fusiform areas showed stronger response decreases to
      repetition of same than different images. A regions-of-interest analysis
      focussing specifically on face responsive regions suggested differences in the
      degree of image dependency across fusiform cortex. Collapsing across familiarity,
      there was greater image dependency of repetition effects in right than left
      anterior fusiform, replicating previous imaging findings obtained with common
      objects. For familiar faces alone, there was greater generalisation of repetition
      effects over different images in anterior than middle fusiform. This suggests a
      role of anterior fusiform cortex in coding image-independent representations of
      familiar faces.

PMID- 15961050
TI  - Retrieving rules for behavior from long-term memory.
AB  - Human behavior is often dictated by rules or prescribed guides for action. Little
      is currently known regarding how these rules are stored in long-term memory or
      retrieved and implemented. Here, we examined the roles of ventrolateral
      prefrontal cortex (VLPFC) and posterior middle temporal gyrus (postMTG) in rule
      use. We tested two hypotheses: first, that knowledge about actions associated
      with abstract visual symbols is stored in postMTG, and second, that VLPFC is
      involved in the controlled retrieval of rule meanings. Subjects viewed a series
      of road signs during event-related fMRI data collection. Three types of signs
      were intermixed: highly familiar signs, novel signs whose meaning was explained
      to subjects prior to scanning, and novel signs whose meaning was not explained.
      Subjects were asked to think about the meaning of each sign as it was presented
      during scanning and then to give its meaning in a post-scan test. Left postMTG
      was more active when subjects viewed signs whose meaning they knew than signs
      whose meaning they did not know, consistent with a role in storing rule meanings.
      This region was not modulated by experience, in that it was equally engaged by
      newly trained and well-learned signs. In contrast, right VLPFC was more active
      for newly trained signs than for either well-learned or incorrect ones,
      consistent with a role in controlled retrieval. Left VLPFC was reliably engaged
      while subjects attempted to interpret the signs but did not differ according to
      knowledge or experience. These data implicate postMTG in rule storage and VLPFC
      in rule retrieval.

PMID- 15961051
TI  - Diffusion tensor imaging of neurodevelopment in children and young adults.
AB  - Diffusion tensor magnetic resonance imaging (DTI) was used to study regional
      changes in the brain's development from childhood (8-12 years, mean 11.1 +/- 1.3,
      N = 32) to young adulthood (21-27 years, mean 24.4 +/- 1.8, N = 28). Mean
      diffusivity (Trace/3 apparent diffusion coefficient, ADC) and fractional
      anisotropy (FA) were measured in 30 regions of interest (ROIs) in 13 distinct
      brain structures. Correlational analysis was performed to detect changes within 8
      12 years and within 21-27 years, and group analysis to compare childhood
      diffusion properties with young adult values. Increases of fractional anisotropy
      were seen in the genu of the corpus callosum, splenium of the corpus callosum,
      corona radiata, putamen, and head of the caudate nucleus within 8-12 years, and
      also between childhood and young adulthood. Reductions in Trace/3 ADC were
      observed in 9 of 13 structures within 8-12 years and into young adulthood as
      well. DTI demonstrates more widespread changes in the brain's microstructure with
      maturation than previous reports using conventional T1-weighted MRI scans. These
      findings suggest a continuation of the brain's microstructural development
      through adolescence.

PMID- 15961052
TI  - Virtual 10-20 measurement on MR images for inter-modal linking of transcranial
      and tomographic neuroimaging methods.
AB  - It is important to create a link between stereotaxic coordinates and head-surface
      based positioning systems in order to share data between tomographic and
      transcranial brain mapping studies. In our previous studies, we established the
      probabilistic correspondence of the international 10-20 positions to the standard
      stereotaxic coordinate systems and made a reference database. However, its
      expansion required the physical marking of the 10-20 positions and the subsequent
      acquisition of MR images. To avoid such tedious procedures, we developed a
      virtual 10-20 measurement algorithm that can be applied to re-analyze any
      structural MR image that covers the whole head. As in the physical 10-20
      measurements, with the reference points given, the algorithm automatically
      determines each 10-20 position step by step. Using the virtual 10-20 measurement
      method, we re-analyzed the MR images of 17 healthy subjects for whom we had
      determined 10-20 positions by physical marking in our previous study. The
      acquired 10-20 positions were normalized to the Montreal Neurological Institute
      (MNI) stereotactic coordinates and compared with the positions previously
      determined by physical measurements. 10-20 positions determined using the virtual
      and physical methods were roughly consistent. Average standard deviations for
      virtual and physical methods were 7.7 mm and 9.0 mm, respectively. There was a
      systematic shift in the virtual method, likely due to the absence of hair
      interference. We corrected the shift with affine transformation. The virtual 10
      20 measurement method proved to be an effective alternative to physical marking.
      This method will serve as an essential tool for expanding the reference database
      and will further strengthen the link between tomographic and transcranial brain
      mapping methods.

PMID- 15961053
TI  - The role of the human amygdala in the production of conditioned fear responses.
AB  - The amygdala plays a central role in the acquisition and expression of fear
      memories. Laboratory animal studies indicate that the amygdala both receives
      sensory information and produces learned behavioral and autonomic fear responses.
      However, prior functional imaging research in humans has largely focused on
      amygdala activity elicited by fearful stimuli, giving less attention to this
      region's role in the production of fear responses. In contrast, the present study
      used functional magnetic resonance imaging to investigate the amygdala's
      influence on the generation of conditional fear responses. Significant increases
      in amygdala activity were observed during the production of conditioned (learning
      related), but not orienting, nonspecific, and unconditioned (nonlearning-related)
      skin conductance responses. Further, greater amygdala activity was demonstrated
      during conditioned response production than during conditioned stimulus
      presentation. These results suggest the amygdala not only responds to fearful
      stimuli, but also generates learning-related changes in human autonomic fear
      expression.

PMID- 15961054
TI  - Quantification of brain phosphodiesterase 4 in rat with (R)-[11C]Rolipram-PET.
AB  - OBJECTIVE: Phosphodiesterase 4 (PDE4) catabolizes the second messenger 3', 5'
      cyclic adenosine monophosphate and may play a critical role in brain diseases.
      Our aim was to quantify PDE4 in rats with positron emission tomography (PET).
      METHODS: High (n = 6) and low specific activity (SA) (n = 2) higher affinity ((R)
      [(11)C]rolipram) and high SA lower affinity ((S)-[(11)C]rolipram) (n = 2)
      enantiomers were intravenously administered to Sprague-Dawley rats. Brain data
      were acquired using the ATLAS PET scanner and reconstructed using the 3D-ordered
      subset expectation maximization algorithm. Arterial samples were taken to measure
      unmetabolized [(11)C]rolipram. Total distribution volumes (V(T)') were calculated
      using a 1-tissue compartment (1C) and an unconstrained 2-tissue compartment (2C)
      model. RESULTS: High SA R experiments showed later and greater brain uptake, and
      slower washout than low SA R and S experiments. In all regions and in all
      experiments, the 2C model gave significantly better fitting than the 1C model.
      The poor fitting by the latter caused underestimation of V(T)' by 19-31%. The 2C
      model identified V(T)' reasonably well with coefficients of variation less than
      10%. V(T)' values by this model were 16.4-29.2 mL/cm(3) in high SA R, 2.9-3.5 in
      low SA R, and 3.1-3.7 in S experiments. CONCLUSIONS: Specific binding of (R)
      [(11)C]rolipram was accurately measured in living rats. In high SA R experiments,
      approximately 86% of V(T)' was specific binding. Distribution and changes of PDE4
      in animal models can now be studied by measuring V(T)' of high SA (R)
      [(11)C]rolipram.

PMID- 15961056
TI  - Irreversible adsorption of particles on heterogeneous surfaces.
AB  - Methods of theoretical and experimental evaluation of irreversible adsorption of
      particles, e.g., colloids and globular proteins at heterogeneous surfaces were
      reviewed. The theoretical models were based on the generalized random sequential
      adsorption (RSA) approach. Within the scope of these models, localized adsorption
      of particles occurring as a result of short-ranged attractive interactions with
      discrete adsorption sites was analyzed. Monte-Carlo type simulations performed
      according to this model 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
      = lambda2theta(s) > 1 the jamming coverage at the heterogeneous surfaces attained
      the value pertinent to continuous surfaces. The results obtained prove
      unequivocally that spherically shaped sites were more efficient in binding
      particles in comparison with disk-shaped sites. It also was predicted that for
      particle size ratio lambda < 4 the site multiplicity effect plays a dominant
      role, affecting significantly the structure of particle monolayers and the
      jamming coverage. Experimental results validating main aspects of these
      theoretical predictions also have been reviewed. These results were derived by
      using monodisperse latex particles adsorbing on substrates produced by covering
      uniform surface by adsorption sites of a desired size, coverage and surface
      charge. Particle deposition occurred under diffusion-controlled transport
      conditions and their coverage was evaluated by direct particle counting using the
      optical and electron microscopy. Adsorption kinetics was quantitatively
      interpreted in terms of numerical solutions of the governing diffusion equation
      with the non-linear boundary condition derived from Monte-Carlo simulations. It
      was proven that for site coverage as low as a few percent the initial flux at
      heterogeneous surfaces attained the maximum value pertinent to homogeneous
      surfaces. It also was demonstrated that the structure of larger particle
      monolayers, characterized in terms of the pair correlation function, showed much
      more short-range ordering than predicted for homogeneous surface monolayers at
      the same coverage. The last part of this review was devoted to detection of
      polyelectrolyte multilayers on various substrates via particle deposition
      experiments.

PMID- 15961057
TI  - Electrospray ionization and tandem mass spectrometry of eicosanoids.

PMID- 15961058
TI  - Gold layer-based dual crosslinking procedure of glucose oxidase with ferrocene
      monocarboxylic acid provides a stable biosensor.

PMID- 15961059
TI  - A role of salivary carbonic anhydrase VI in dental plaque.
AB  - OBJECTIVE: Carbonic anhydrase (CA) VI is a unique secreted isozyme of CA, which
      catalyzes the reversible reaction CO2 +H2O<-->H+ +HCO3-. CA VI has been thought
      to provide a greater buffering capacity to fluids into which it is secreted. This
      study was performed to confirm this in saliva. DESIGN: Nine healthy subjects
      participated in the study. The pH of the dental plaque from each subject was
      monitored after a mouth rinse with 10% sucrose with or without 10(-5)M
      acetazolamide, a specific inhibitor of CA. Also CA was examined in plaque by
      enzyme histochemistry, immunohistochemistry and Western blot analysis. RESULTS:
      Though sucrose and sucrose plus inhibitor yielded Stephan curves with a similar
      temporal pattern, the pH values of the latter were significantly lower than those
      of the former. Plaque exhibited CA activity by enzyme histochemistry.
      Immunohistochemistry and Western analysis demonstrated that the activity was due
      to CA VI but not to CA I or CA II. CONCLUSIONS: The results indicate that CA VI
      in saliva penetrates plaque and facilitates acid neutralization by salivary
      bicarbonate. Therefore, CA VI may be considered an anti-caries protein in saliva.

PMID- 15961060
TI  - Escherichia coli fusion carrier proteins act as solubilizing agents for
      recombinant uncoupling protein 1 through interactions with GroEL.
AB  - Fusing recombinant proteins to highly soluble partners is frequently used to
      prevent aggregation of recombinant proteins in Escherichia coli. Moreover, co
      overexpression of prokaryotic chaperones can increase the amount of properly
      folded recombinant proteins. To understand the solubility enhancement of fusion
      proteins, we designed two recombinant proteins composed of uncoupling protein 1
      (UCP1), a mitochondrial membrane protein, in fusion with MBP or NusA. We were
      able to express soluble forms of MBP-UCP1 and NusA-UCP1 despite the high
      hydrophobicity of UCP1. Furthermore, the yield of soluble fusion proteins
      depended on co-overexpression of GroEL that catalyzes folding of polypeptides.
      MBP-UCP1 was expressed in the form of a non-covalent complex with GroEL. MBP
      UCP1/GroEL was purified and characterized by dynamic light scattering, gel
      filtration, and electron microscopy. Our findings suggest that MBP and NusA act
      as solubilizing agents by forcing the recombinant protein to pass through the
      bacterial chaperone pathway in the context of fusion protein.

PMID- 15961061
TI  - Environmental enrichment and neurodegenerative diseases.
AB  - Recent reports on experimental models of neurodegeneration in mice have
      strengthened the notion that environmental enrichment (EE) is beneficial, in
      terms of delayed onset and progression, to a variety of neurodegenerative
      diseases. These studies also revealed interesting mechanistic understandings as
      to how EE might function. While it is generally assumed that EE elicits
      transcriptional and translational events that on the whole tend to be
      neuroprotective and neurogenic, fairly specific changes that appear to target the
      underlying pathological causes of disease in these various mouse models have been
      noted. These include a possible restoration of brain-derived neurotrophic factor
      striatal transport in the R6/1 Huntington's mice and an elevation in the levels
      of amyloid-degrading enzyme neprilysin in the APPswe/PS1DeltaE9 Alzheimic mice.
      An elevation in glial-derived neurotrophic factor coupled to a reduction in
      dopamine transporter may underlie beneficial effects in mice with 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonian symptoms. How all these
      findings would translate to disease settings in human patients are unclear, but
      they do provide useful leads for further clinical and paraclinical
      investigations.

PMID- 15961062
TI  - nanor, a novel zygotic gene, is expressed initially at the midblastula transition
      in zebrafish.
AB  - A novel, developmentally regulated gene, nanor, was identified by suppression
      subtractive hybridization. It is first expressed following the midblastula
      transition (MBT), a critical developmental stage in the early vertebrate embryo
      when the zygotic genome is activated. The nanor cDNA (626bp) includes a complete
      open reading frame but neither the gene nor the deduced amino acid sequence shows
      significant similarity to any known gene or protein. Nanor encodes a 175 amino
      acid putative protein with a protein kinase C and three casein kinase II
      phosphorylation sites, an N-myristoylation site and an NFX-type zinc-finger
      domain, indicating a potential role in transcriptional regulation. Semi
      quantitative RT-PCR, Northern blot, and in situ hybridization analysis revealed
      that nanor expression is developmentally regulated. It is initially expressed
      after the MBT at the sphere stage and during epiboly it is expressed in the
      forerunner cells. At 24 h post-fertilization, expression is solely anterior.

PMID- 15961063
TI  - Bevacizumab (Avastin), a humanized anti-VEGF monoclonal antibody for cancer
      therapy.
AB  - Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen
      in vitro and an angiogenic inducer in vivo. The tyrosine kinases Flt-1 (VEGFR-1)
      and Flk-1/KDR (VEGFR-2) are high affinity VEGF receptors. VEGF plays an essential
      role in developmental angiogenesis and is important also for reproductive and
      bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of
      pathological angiogenesis. Anti-VEGF monoclonal antibodies and other VEGF
      inhibitors block the growth of several tumor cell lines in nude mice. Clinical
      trials with VEGF inhibitors in a variety of malignancies are ongoing. Recently, a
      humanized anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved
      by the FDA as a first-line treatment for metastatic colorectal cancer in
      combination with chemotherapy. Furthermore, VEGF is implicated in intraocular
      neovascularization associated with diabetic retinopathy and age-related macular
      degeneration.

PMID- 15961064
TI  - In vitro differentiation characteristics of cultured human mononuclear cells
      implications for endothelial progenitor cell biology.
AB  - Endothelial progenitor cells (EPCs) have been implicated in the pathogenesis and
      treatment of cardiovascular disease. By use of quantitative uptake of DiLDL and
      lectin staining, EPCs have been characterized reliably. However, the exact nature
      and function of this cell population still remains poorly defined. In an attempt
      to further clarify the cell surface characteristics of EPCs, mononuclear cells
      (MNCs) were isolated from human blood and cell surface expression patterns were
      defined by FACS analysis before and after differentiation for 1-10 days in cell
      culture. "Classical" double staining for DiLDL and Ulex europaeus increases to
      89.2 /- 0.05 after 10 days in culture. Looking at EPC-specific markers by FACS
      analysis, 0.18 +/- 0.11% of freshly isolated MNCs express CD34, 0.13 +/- 0.08%
      CD133, 0.59 +/-0.51% VEGFr2, 0.01 +/- 0.02% CD34/VEGFr2, 0.09 +/- 0.05%
      CD34/CD133, 0.58 +/- 0.13% CD34/CD31, and 0.02 +/- 0.01% CD34/CD146,
      respectively. Induction of the endothelial phenotype is evidenced by positive
      staining for VEGFr2, CD146, and CD31, and occurs in co-expression with stem cell
      markers in less than 2 +/- 0.52% of cultured cells. Expression of CD34 increases
      to 0.38 +/- 0.10% after 10 days, whereas the CD133(+) cell population shows an
      initial peak at 24h (0.29 +/- 0.18%) before decreasing to 0.15 +/- 0.02% at day
      10. EPCs co-expressing CD34/CD133 increase to 0.19 +/- 0.09% after 10 days, and
      EPCs double-positive for CD34/VEGFr2 increase to 1.45 +/- 1.03%. Looking at
      leukocyte, lymphocyte, and monocyte lineage markers, 56.27 +/- 0.15% of freshly
      isolated MNCs express CD45, 7.13 +/- 0.02% CD14, and 38.65 +/- 0.01% CD3. Over
      the 10-day culture period, expression of CD45 decreases to 28.48 +/- 0.18%, CD3
      to 23.11 +/- 0.02%, and CD14 to 0.09 +/- 0.02%. Cells co-expressing CD3/CD45
      decrease from 38.88 +/- 0.33% to 24.86 +/- 2.49% after 10 days in culture. These
      findings extend present knowledge by showing that human MNCs differentiate at a
      very low rate to EPCs, while a majority of the cultured cell population remain
      committed to the leukocyte or lymphocyte lineage. Careful surface marker analysis
      might be necessary when using in vitro EPC differentiation systems.

PMID- 15961065
TI  - Thrombophilia in mice expressing a tissue factor variant lacking its
      transmembrane and cytosolic domain.
AB  - Mice with a targeted truncation in the gene encoding tissue factor of blood
      coagulation (TF) to eliminate the cytosolic domain and carrying a neo(R) cassette
      in intron 5 unexpectedly displayed severe spontaneous thrombosis in various
      vascular beds. Thrombosis was observed in heterozygous TF(+/neo) mice, causing
      death of over 50% of adults within 36 weeks of birth, and fulminantly
      exacerbating in pregnant females. Homozygous TF(neo/neo) mice were more severely
      affected and died within 7 weeks after birth. These TF(neo) mice primarily
      synthesized a mutant mRNA aberrantly spliced from exon 5 to neo(R), encoding an
      apparently non-vesicle-binding soluble TF lacking both the transmembrane and
      cytosolic domain, but still capable of blood coagulation induction. This severe
      thrombotic phenotype associated with the presence of a non-anchored soluble TF
      variant underscores the recently recognized significance of circulating TF for
      thrombus formation and development.

PMID- 15961066
TI  - Irsogladine maleate influences the response of gap junctional intercellular
      communication and IL-8 of human gingival epithelial cells following
      periodontopathogenic bacterial challenge.
AB  - Gingival epithelial cells first encounter periodontopathogenic bacteria and their
      metabolic products to produce inflammatory cytokines. Gap junctional
      intercellular communication (GJIC) is thought to play a critical role in cellular
      coordination in tissue homeostasis. Gap junctions are structured by connexins
      (CXs). GJIC response of gingival epithelial cells to the bacteria may be involved
      in the initiation of periodontal disease. Irsogladine maleate (IM) is known to
      enhance GJIC through cAMP. In the present study, we examined an effect of IM on
      GJIC response and on interleukin-8 (IL-8) levels in human gingival epithelial
      cells (HGEC) exposed to a periodontopathogenic bacterium, Actinobacillus
      actinomycetemcomitans, and its outer membrane protein (OMP) 29 in order to test
      the hypothesis that IM has the ability to modulate GJIC and inflammatory
      responses of gingival epithelial cells to periodontopathogenic bacteria. IM
      countered the OMP29-induced reduction of GJIC, CX43 levels and cAMP levels in
      HGEC. The simultaneous addition of OMP29 and dibutyryl cAMP also abrogated the
      repression of GJIC by OMP29. Furthermore, IM obviated the increase in IL-8 levels
      in HGEC stimulated by whole live A. actinomycetemcomitans and by OMP29. These
      findings suggest that IM counters the OMP29-induced GJIC reduction in HGEC
      through cAMP. IM may eliminate initial perturbation of gingival epithelial cells
      by regulating responses of GJIC and IL-8 to periodontopathogenic bacterial
      exposure.

PMID- 15961067
TI  - A role for prefrontal cortex in the extinction of a conditioned taste aversion.
AB  - This study used immunohistochemical methods to determine if the medial prefrontal
      cortex (mPFC) is involved in the extinction of a conditioned taste aversion
      (CTA). As rats reached 90% reacceptance of a tastant (saccharin: SAC) that had
      previously been associated with lithium chloride-induced malaise, c-Fos protein
      expression increased dramatically as compared to animals with active CTAs,
      animals without CTAs (i.e., explicitly unpaired CS-US exposures) or animals
      drinking SAC for the first time. These data indicate a role for mPFC (prelimbic
      and infralimbic cortex) in the formation of a CTA extinction memory.

PMID- 15961068
TI  - The critical threshold of 3-nitropropionic acid-induced ischemic tolerance in the
      rat.
AB  - 3-Nitropropionic acid (3-NPA) is a suicide inactivator of succinate dehydrogenase
      (SDH), commonly used as a pharmacological model of Huntington's disease in
      rodents. Several studies have shown that a single administration of 3-NPA given
      systemically provides subsequent ischemic tolerance. The present study has tested
      the hypothesis that 3-NPA is capable of inducing tolerance in a model of
      permanent focal cerebral ischemia and whether 3-NPA can be truly applicable as a
      tolerance-inducer to ischemia. Rats given 3-NPA intraperitoneally revealed that
      the mortality of 3-NPA of 15, 20, and 25 mg/kg groups was 20.5, 38.8, and 83.3%,
      respectively. All rats survived without behavioral sequelae at smaller doses.
      Three days after 3-NPA preconditioning, the rats showing no behavioral changes
      underwent the permanent middle cerebral artery occlusion. The groups treated with
      10 and 15 mg/kg of 3-NPA showed significantly reduced neurological deficits and
      infarction volumes in comparison with the control group, whereas the groups
      treated with 5 and 20 mg/kg of 3-NPA revealed no tolerance effects. When the
      regional SDH activity (% of control) was photometrically semi-quantified, it was
      observed that the activity was reduced to 90.8, 76.1, 67.8, and 64.3% in the
      outer layers of the cerebral cortex, and to 79.4, 67.5, 63.2, and 62.9% in the
      striatum 1 h after 3-NPA application (5, 10, 15, 20 mg/kg), respectively. In
      conclusion, although the preconditioning with 3-NPA is clearly shown in the
      setting of permanent ischemia, the preconditioning with this mitochondrial toxin
      demonstrated a rather narrow safety margin (critical threshold).

PMID- 15961069
TI  - Focal adhesion kinase mediates MEF2 and c-Jun activation by stretch: role in the
      activation of the cardiac hypertrophic genetic program.
AB  - OBJECTIVE: We have previously reported that myocyte enhancer factor-2 (MEF2)
      transcription factors and c-Jun are rapidly activated by pressure overload and
      that these events are involved in the early activation of the myocardial
      hypertrophic genetic program. In this study, we investigated whether focal
      adhesion kinase (FAK) mediates the activation of MEF2 and c-Jun by mechanical
      stress in isolated neonatal rat ventricular myocytes (NRVMs). METHODS: NRVMs were
      subjected to cyclic stretch up to 4 h and studied by immunoblotting, reverse
      transcriptase-polymerase chain reaction, laser confocal analysis, and reporter
      gene and electrophoretic mobility shift assays. Analysis was extended to NRVMs
      transfected with FAK-antisense oligodeoxynucleotide, treated with FAK/Src
      inhibitor PP2 or JNK/c-Jun inhibitor SP600125. RESULTS: Cyclic stretch increased
      c-Jun expression, JNK/c-Jun phosphorylation, and MEF2-DNA binding activity in
      NRVMs. Reporter gene assays indicated that the MEF2 site is critical to c-jun
      transcription in stretched cells. FAK-antisense transfection abolished MEF2 and c
      jun promoter activation, while either FAK-antisense or PP2 treatment inhibited
      the stretch-induced c-Jun expression and JNK/c-Jun phosphorylation. Finally,
      treatment of NRVMs with the specific JNK/c-Jun inhibitor SP600125 significantly
      reduced the stretch-induced increase of atrial natriuretic factor promoter
      activity. CONCLUSION: The present data indicate that FAK regulates the activation
      of MEF2 and JNK/c-Jun pathways, which in turn have a key role in the early
      activation of the hypertrophic genetic program by mechanical stress in cardiac
      myocytes.

PMID- 15961071
TI  - When is bioavailable testosterone a redundant test in the diagnosis of
      hypogonadism in men?
AB  - OBJECTIVES: Total testosterone (TT) is frequently prescribed with an SHBG and/or
      free or bioavailable testosterone measurement. Our objective was to identify a TT
      range for which subsequent SHBG measurement/calculation adds no additional
      clinical information. DESIGN AND METHODS: Study data were composed of 3955 sets
      of TT, SHBG and calculated bioavailable testosterone (cBAT) results from
      unscreened ambulatory male subjects, aged 18-99. RESULTS: 90% of mismatches
      between TT and cBAT were observed with TT levels between 6.5 and 13.0 nmol/L,
      with only slight age variation and no important change with albumin level. SHBG
      measurement restricted to male patients with TT between 6.5 and 13.0 nmol/L
      should enable reagent cost savings of over 55%. CONCLUSION: We suggest that a TT
      level below 6.5 nmol/L or above 13.0 nmol/L provides sufficient useful
      information for ruling out hypogonadism in ambulatory adult males. This strategy
      of BAT testing should lead to significant time and cost savings.

PMID- 15961070
TI  - A simple binding assay for the direct determination of biotin in urine.
AB  - BACKGROUND: We have devised a simple assay to detect adequate biotin intake,
      which uses an alternative configuration from most existing assays. METHODS: The
      assay depends on the competition of streptavidin peroxidase for immobilized
      biotin or soluble biotin in standards or samples. Immobilized streptavidin
      peroxidase is detected using tetramethylbenzidine, and the plates are read at 450
      nm. The assay was normalised by determining the biotin/creatinine ratio in the
      urine of healthy adults. Urinary biotin excretion was measured in unsupplemented
      pregnant women. The half-life of biotin excretion after a single oral supplement
      was determined for healthy volunteers. RESULTS: Urinary biotin excretion in
      unsupplemented pregnant women was 2.9+/-1.9 micromol/mol creatinine (mean+/-S.D.)
      and was significantly lower (p<0.001) than those of healthy males and females,
      which were 9.0+/-5.4 and 7.0+/-2.1 micromol/mol creatinine (mean+/-S.D.),
      respectively. The half-life of a single oral biotin supplement was 30-40 h, with
      excretion returning to basal levels at 70 h. CONCLUSION: We have devised a novel
      binding assay for the direct determination of total biotin excretion in urine,
      which is suitable for routine clinical laboratory. The assay is inexpensive,
      simple, rapid, and could be fully automated.

PMID- 15961072
TI  - Homocysteine, a risk factor for atherosclerosis, biphasically changes the
      endothelial production of kynurenic acid.
AB  - Increased serum level of homocysteine is an independent risk factor for vascular
      disease. The effect of DL-homocysteine on the endothelial production of kynurenic
      acid, an antagonist of alpha7-nicotinic and N-methyl-D-aspartate (NMDA) glutamate
      receptors, has been evaluated in vitro and in vivo. In rat aortic rings, DL
      homocysteine at 40-100 microM enhanced, whereas at >or=400 microM decreased the
      synthesis of kynurenic acid. S-adenosylhomocysteine mimicked the biphasic action
      of DL-homocysteine. On the contrary, thiol-containing compounds, L-cysteine and L
      methionine, were only inhibiting kynurenic acid production. L-kynurenine uptake
      blockers, L-phenylalanine and L-leucine, reversed the stimulatory effect of S
      adenosylhomocysteine. L-glycine, co-agonist of NMDA receptor, and cis-4
      phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), an antagonist of NMDA
      receptor, have not influenced kynurenic acid formation. In vivo, DL-homocysteine
      (1.3 mmol, i.p.) increased the level of kynurenic acid in rat serum from 23.7+/
      7.1 to 60.7+/-14.2 (15 min, P<0.01) and 55.7+/-13.6 (60 min, P<0.01) pmol/ml,
      respectively; the endothelial content of kynurenic acid was also increased
      (51.6+/-5.8 vs. 73.2+/-9.4 fmol/microg of protein; 15 min; P<0.01). DL
      homocysteine seems to modulate the production of kynurenic acid both directly and
      indirectly, possibly following the conversion to S-adenosylhomocysteine. The
      obtained data suggest a potential contribution of altered formation of kynurenic
      acid to the endothelial changes induced by hyperhomocysteinemia.

PMID- 15961073
TI  - Inhibitory effect of JTP-59557, a new triazole derivative, on intestinal
      phosphate transport in vitro and in vivo.
AB  - JTP-59557 [(-)-4-(2-tert-Butyl-4,5-dichlorophenyl)-5-(5-trifluoromethylpyridin-2
      ylsulfanyl)-4H-[1,2,4]triazol-3-ol] showed an inhibitory effect on Na(+)
      dependent inorganic phosphate (Pi) transport in intestinal brush border membrane
      vesicles with an IC(50) value of 0.40 microM in rabbit and with an IC(50) of 0.19
      microM in rat, without affecting Na(+)-independent Pi and Na(+)-dependent d
      glucose transport activities. In Chinese hamster ovary (CHO) cells expressing
      human type IIb Na/Pi cotransporter (type IIb), JTP-59557 decreased human type IIb
      mediated Pi uptake with an IC(50) of 0.12 microM. In rabbit intestinal brush
      border membrane vesicles, JTP-59557 behaved as a noncompetitive inhibitor with
      respect to Pi. In an in vivo study, single administration of JTP-59557
      significantly decreased the intestinal Pi absorption rate, when either Pi
      solution or laboratory chow was given to rats. In this report, we show that JTP
      59557 is a potent, selective, stereospecific, noncompetitive inhibitor of
      intestinal Na/Pi cotransporters including type IIb, and it may represent a new
      class of intestinal Pi absorption inhibitor.

PMID- 15961074
TI  - WIN 55,212-2-induced reduction of cocaine hyperlocomotion: possible inhibition of
      5-HT(3) receptor function.
AB  - We examined the effect of WIN 55,212-2 (an agonist of cannabinoid receptors) and
      its enantiomer WIN 55,212-3, as well as of ondansetron (an antagonist of
      serotonin (5-HT)(3) receptors) on the cocaine-induced locomotor hyperactivity in
      rats. WIN 55,212-2, but not WIN 55,212-3, in doses of 3 and 6 mg/kg which did not
      affect the basal locomotor activity, dose-dependently reduced the hyperactivation
      evoked by cocaine. The inhibitory effect of WIN 55,212-2 was not affected by
      rimonabant (an antagonist of cannabinoid receptors). Like in the case of WIN
      55,212-2, the cocaine-induced hyperlocomotion was reduced in a dose-dependent
      manner by ondansetron (0.03-0.3 mg/kg). The obtained results indicate that the
      inhibitory effect of WIN 55,212-2 on cocaine hyperactivation is stereoselective
      and is not mediated by cannabinoid receptors. Moreover, together with the
      literature data they may suggest that this effect of WIN 55,212-2 involves
      inhibition of the 5-HT(3) receptor function.

PMID- 15961075
TI  - Intermittent short-duration exposure to low wall shear stress induces intimal
      thickening in arteries exposed to chronic high shear stress.
AB  - We sought to determine whether intermittent short-duration exposure to low wall
      shear stress could induce intimal thickening in arteries chronically exposed to
      high shear stress. An arteriovenous fistula (AVF) was created between the left
      common carotid artery and the corresponding external jugular vein in 20 Japanese
      white male rabbits. After 4 weeks, blood flow was increased 10-fold to 182 +/- 39
      ml/min and shear stress was increased to 33.4 +/- 13 dyn/cm(2). The AVF was then
      occluded for 1 h by finger compression with an 85% reduction in carotid artery
      blood flow (27 +/- 7 ml/min) and a reduction in wall shear stress to 4.9 +/- 1.7
      dyn/cm(2) (P < 0.0001). Release of finger compression restored flow to the AVF
      and high shear stress to the carotid artery. This procedure was repeated at
      weekly intervals with a cumulative total of 4 h of low shear stress exposure.
      Arteries exposed to intermittent low shear stress developed a layer of intimal
      thickening which consisted of 3-4 layers of smooth muscle cells lined with thin
      elastic fibers and medial hyperplasia. Control arteries exposed to 8 weeks of
      continuous high shear had no intimal thickening. Transient exposure to low shear
      stress upregulated TGF-beta1, MMP-2, -14, and TIMP-2 gene expression while MMP-9
      expression was downregulated. We conclude that repeated, intermittent short
      duration exposure to low shear stress in the setting of high flow and high shear
      stress can induce arterial intimal thickening. Short-duration alterations in
      hemodynamic forces can induce rapid vascular cell message expression, which may
      effect arterial remodeling. This experiment suggests that a threshold value of 5
      dyn/cm(2) may be needed in order to initiate and sustain the intimal thickening
      response.

PMID- 15961076
TI  - Circulating fragmented nucleosomal DNA and caspase-3 mRNA in patients with
      lymphoma and myeloma.
AB  - Elevated amounts of cell-free nucleic acids are detected in the circulation of
      cancer patients. The type and pattern of these may vary depending on the origin.
      Recently, we described the presence of circulating fragmented nucleosomal DNA. In
      the present study, our aim was to investigate the association between nucleosomal
      DNA, caspase-3 expression and circulating caspase-3 mRNA, the primary activator
      of nucleosomal DNA fragmentation. DNA fragmentation was analyzed by gel
      electrophoresis, and caspase-3 was analyzed by RT-PCR. Plasma samples from 65% of
      patients were positive for nucleosomal DNA fragmentation, whereas none of the
      healthy controls showed DNA fragmentation (P = 0.0004). Expression of caspase-3
      differed significantly between the cases and controls (P < 0.0001). However, we
      observed no direct correlation between nucleosomal DNA fragmentation and caspase
      3 expression in lymphocytes (P = 0.145). Circulating plasma caspase-3 mRNA was
      detected by nested RT-PCR, and no significant difference was observed between the
      patients and the control group (P = 0.5). Our results indicate that caspase-3
      expression is increased in lymphocytes from patients. When compared to healthy
      individuals, no differences were observed in the amount of circulating mRNA.
      These findings suggest that nucleosomal DNA fragmentation is not correlated with
      elevated levels of apoptosis and circulating caspase-3 mRNA in circulating tumor
      cells.

PMID- 15961077
TI  - Plasmodium berghei NK65: studies on the effect of treatment duration and inoculum
      size on recrudescence.
AB  - Recrudescence of Plasmodium berghei NK65 infection was studied to examine factors
      affecting recrudescence. Treatment with a high dose of chloroquine did not
      prevent recrudescence, but an extended duration of treatment suppressed the
      frequency of recrudescence. Infection with a larger number of parasites also
      resulted in more frequent recrudescences. Recrudescent parasites were as
      sensitive to chloroquine as those before treatment. Splenectomized mice were
      administered carbon particles, infected, and treated with chloroquine.
      Recrudescence was significantly more frequent in these mice than in mice given a
      sham operation and PBS. The results do not suggest that merozoite stages escape
      the effect of chloroquine by 'hiding' in phagocytes, but that latent parasites
      such as dormant ring stages may cause recrudescence.

PMID- 15961078
TI  - Oxidized SOD1 alters proteasome activities in vitro and in the cortex of SOD1
      overexpressing mice.
AB  - Premature ageing, one of the characteristics of Down syndrome (DS), may involve
      oxidative stress and impairment of proteasome activity. Transgenic mice
      overexpressing the human copper/zinc superoxide dismutase (SOD1) gene are one of
      the first murine models for DS and it has been shown that SOD1 overexpression
      might be either deleterious or beneficial. Here, we show a reduction in
      proteasome activities in the cortex of SOD1 transgenic mice and an associated
      increase in the content of oxidized SOD1 protein. As we demonstrate that in vitro
      oxidized SOD can inhibit purified proteasome peptidase activities, modified SOD1
      might be partially responsible for proteasome inhibition shown in SOD1 transgenic
      mice.

PMID- 15961079
TI  - Down-regulation of the tumor suppressor gene C-terminal Src kinase: an early
      event during premalignant colonic epithelial hyperproliferation.
AB  - Hyperproliferation of the premalignant epithelium is critical for colonic
      carcinogenesis; however the mechanisms remain largely unexplored. We report
      herein that prior to occurrence of neoplastic lesions in the azoxymethane-rat
      model of colon carcinogenesis; the tumor suppressor gene C-terminal Src kinase
      (Csk) was down-regulated with a concomitant increase in Src activity.
      Furthermore, pharmacological or genetic (RNA interference) inhibition of Csk
      resulted in increased proliferation in colon cancer cell lines through the
      mitogen-activated protein kinase dependent pathway. Thus, we demonstrate, for the
      first time, that Csk suppression is an important early event in colorectal cancer
      pathogenesis.

PMID- 15961080
TI  - Decreased stability of photosystem I in dgd1 mutant of Arabidopsis thaliana.
AB  - The dgd1 mutant of Arabidopsis thaliana provides us with a powerful tool for
      revealing the specific role of digalactosyldiacylglycerol (DGDG) in
      photosynthesis. Blue-native polyacrylamide gel electrophoresis analysis revealed
      that photosystem I (PSI) subunits are assembled into a PSI complex, and that a
      PSI subcomplex lacking stroma side subunits was also present. PSI subunits in the
      dgd1 mutant were decreased to a similar level compared with that in the wild type
      (WT) Arabidopsis. Further experiments showed that PSI subunits in the stroma
      side, PsaD and PsaE, in the dgd1 mutant were more susceptible to removal by
      chaotropic agents than those in the WT plant, indicating that the stability of
      PsaD and PsaE is impaired in the dgd1 mutant. These results provide evidence that
      DGDG is important for the stability of the PSI complex.

PMID- 15961081
TI  - Expression of pro-apoptotic Bfk isoforms reduces during malignant transformation
      in the human gastrointestinal tract.
AB  - Reduced expression of pro-apoptotic Bcl-2 family proteins has been described in
      many gastrointestinal cancers, and may play a role in tumourigenesis. The human
      homologue of the pro-apoptotic Bcl-2 protein, Bfk, is predominantly expressed in
      tissues of the gastrointestinal tract. In colon, four alternatively spliced
      isoforms were identified; of which two are pro-apoptotic when overexpressed. In
      the transition from normal tissue to tumour, pro-apoptotic Bfk isoform expression
      is substantially reduced in up to 80% of tumours isolated from the human
      gastrointestinal tract (8/10 colonic tumours and 26/37 of all gastrointestinal
      tumours) compared to 3/117 tumours from outside the gastrointestinal tract. These
      data suggest that pro-apoptotic isoforms of Bfk may help to protect against the
      development of human gastrointestinal malignancy.

PMID- 15961082
TI  - Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose
      uptake in the heart.
AB  - In order to investigate the importance of the PDK1-PKB-GSK3 signalling network in
      regulating glycogen synthase (GS) in the heart, we have employed tissue specific
      conditional knockout mice lacking PDK1 in muscle (mPDK1-/-), as well as knockin
      mice in which the protein kinase B (PKB) phosphorylation site on glycogen
      synthase kinase-3alpha (GSK3alpha) (Ser21) and GSK3beta (Ser9) is changed to Ala.
      We demonstrate that in hearts from mPDK1-/- or double GSK3alpha/GSK3beta knockin
      mice, insulin failed to stimulate the activity of GS or induce its
      dephosphorylation at residues that are phosphorylated by GSK3. We also establish
      that in the heart, both GSK3 isoforms participate in the regulation of GS, with
      GSK3beta playing a more prominent role. This contrasts with skeletal muscle where
      GSK3beta is the major regulator of insulin-induced GS activity. Despite the
      inability of insulin to stimulate glycogen synthesis in hearts from the mPDK1-/-
      or double GSK3alpha/GSK3beta knockin mice, these animals possessed normal levels
      of cardiac glycogen, demonstrating that total glycogen levels are regulated
      independently of insulin's ability to stimulate GS in the heart and that
      mechanisms such as allosteric activation of GS by glucose-6-phosphate and/or
      activation of GS by muscle contraction, could operate to maintain normal glycogen
      levels in these mice. We also demonstrate that in cardiomyocytes derived from the
      mPDK1-/- hearts, although the levels of glucose transporter type 4 (GLUT4) are
      increased 2-fold, insulin failed to stimulate glucose uptake, providing genetic
      evidence that PDK1 plays a crucial role in enabling insulin to promote glucose
      uptake in cardiac muscle.

PMID- 15961083
TI  - The solution structure of an N-terminally truncated version of the yeast CDC24p
      PB1 domain shows a different beta-sheet topology.
AB  - Phox and Bem1 (PB1) domains mediate protein-protein interactions via the
      formation of homo- or hetero-dimers. The C-terminal PB1 domain of yeast cell
      division cycle 24 (CDC24p), a guanine-nucleotide exchange factor involved in cell
      polarity establishment, is known to interact with the PB1 domain occurring in bud
      emergence MSB1 interacting 1 (BEM1p) during the regulation of the yeast budding
      process via its OPR/PC/AID (OPCA) motif. Here, we present the structure of an N
      terminally truncated version of the Sc CDC24p PB1 domain. It shows a different
      topology of the beta-sheet than the long form. However, the C-terminal part of
      the structure shows the conserved PB1 domain features including the OPCA motif
      with a slight rearrangement of helix alpha1. Residues which are important for the
      heterodimerization with BEM1p are structurally preserved.

PMID- 15961084
TI  - Three-dimensional architecture of phycobilisomes from Nostoc flagelliforme
      revealed by single particle electron microscopy.
AB  - Phycobilisomes are protein complexes that harvest light and transfer energy to
      the photo system. Here, the three dimensional structure of intact phycobilisomes
      from Nostoc flagelliforme is studied by a combination of negative stain electron
      microscopy and cryo-electron microscopy. Results show that the intact
      phycobilisomes are composed of a tricylindrical core and six rods. Each
      allophycocyanin cylinder presents a double-layered structure when viewed from the
      side and a triangular shape when viewed from the top. These characteristics
      indicate that allophycocyanin trimers in the intact phycobilisomes are arranged
      into hexameric oligomers in a parallel manner.

PMID- 15961085
TI  - Synthesis, biological and modeling studies of 1,3-di-n-propyl-2,4-dioxo-6-methyl
      8-(substituted) 1,2,3,4-tetrahydro [1,2,4]-triazolo [3,4-f]-purines as adenosine
      receptor antagonists.
AB  - A new series of potential adenosine receptor antagonists with a [1,2,4]-triazolo
      [3,4-f]-purine structure bearing at the 1 and 3 position n-propyl groups have
      been synthesized, and their affinities at the four human adenosine receptor
      subtypes (A(1), A(2A), A(2B) and A(3)) have been evaluated. In this case the
      presence of n-propyl groups seems to induce potency at the A(2A) and A(3)
      adenosine receptor subtypes as opposed to our previously reported series bearing
      methyl substituents at the 1 and 3 positions. In particular the non-acylated
      derivative 17 showed affinity at these two receptor subtypes in the micromolar
      range. Indeed, preliminary molecular modeling investigations according to the
      experimental binding data indicate a modest steric and electrostatic antagonist
      receptor complementarity.

PMID- 15961086
TI  - Study of electrochemical oxidation and determination of albendazole using a
      glassy carbon-rotating disk electrode.
AB  - In this work, electrochemical oxidation of albendazole (ABZ) was carried out
      using a glassy carbon-rotating disk electrode. Development of electroanalytical
      methodology for ABZ quantification in pharmaceutical formulations was also
      proposed by using linear sweep voltammetric technique. Electrochemical oxidation
      is observed for ABZ at E(1/2)=0.99 V vs. Ag/AgCl(sat), when an anodic wave is
      observed. Kinetic parameters obtained for ABZ oxidation exhibited a standard
      heterogeneous rate constant for the electrodic process equal to (1.51+/-0.07) x
      10(-5) cm s(-1), with a alphan(a) value equal to 0.76. Limiting current
      dependence against ABZ concentration exhibited linearity on 5.0 x 10(-5) to 1.0 x
      10(-2) mol l(-1) range, being obtained a detection limit of 2.4 x 10(-5) mol l(
      1). Proposed methodology was applied to ABZ quantification in pharmaceutical
      formulations.

PMID- 15961087
TI  - Quantitative analysis of bucillamine and its pharmaceutical formulation using FT
      IR spectroscopy.
AB  - A Fourier transform infrared (FT-IR) spectrometric method was developed for the
      rapid, direct measurement of bucillamine. Conventional KBr-spectra and DRIFTS
      spectra were compared for best determination of active substance in its tablet
      formulation. Two chemometric approaches, partial least squares (PLS) and
      principal component regression (PCR+) methods were used in data processing.
      Similar results were obtained with both chemometric methods.

PMID- 15961088
TI  - Attraction thresholds and sex discrimination of urinary odorants in male and
      female aromatase knockout (ArKO) mice.
AB  - We previously found that both male and female aromatase knockout (ArKO) mice,
      which cannot synthesize estrogens due to a targeted mutation of the aromatase
      gene, showed less investigation of volatile body odors from anesthetized
      conspecifics of both sexes in Y-maze tests. We now ask whether ArKO mice are in
      fact capable of discriminating between and/or responding to volatile odors. Using
      habituation/dishabituation tests, we found that gonadectomized ArKO and wild-type
      (WT) mice of both sexes, which were tested without any sex hormone replacement,
      reliably distinguished between undiluted volatile urinary odors of either adult
      males or estrous females versus deionized water as well as between these two
      urinary odors themselves. However, ArKO mice of both sexes were less motivated
      than WT controls to investigate same-sex odors when they were presented last in
      the sequence of stimuli. In a second experiment, we compared the ability of ArKO
      and WT mice to respond to decreasing concentrations of either male or female
      urinary odors. We found a clear-cut sex difference in urinary odor attraction
      thresholds among WT mice: WT males failed to respond to urine dilutions higher
      than 1:20 by volume, whereas WT females continued to respond to urine dilutions
      up to 1:80. Male ArKO mice resembled WT females in their ability to respond to
      lower concentrations of urinary odors, raising the possibility that the observed
      sex difference among WT mice in urine attraction thresholds results from the
      perinatal actions of estrogen in the male nervous system. Female ArKO mice failed
      to show significant dishabituation responses to two (1:20 and 1:80) dilutions of
      female urine, perhaps, again, because of a reduced motivation to investigate less
      salient, same-sex urinary odors. Previously observed deficits in the preference
      of ArKO male and female mice to approach volatile body odors from conspecifics of
      either sex cannot be attributed to an inability of ArKO subjects to discriminate
      these odors according to sex but instead may reflect a deficient motivation to
      approach same-sex odors, especially when their concentration is low.

PMID- 15961089
TI  - Programming the offspring of the pig by prenatal social stress: neuroendocrine
      activity and behaviour.
AB  - This study provides evidence in the pig that stress experienced during gestation
      has long-lasting effects on offspring daughters, including their maternal
      behaviour. Thirty-six primiparous sows were divided into control and two groups
      that were stressed (by social mixing) during either the second (Mix 2) or third
      (Mix 3) trimester of pregnancy. We found detrimental effects of mixing on the
      mothers' growth, body lesions, and cortisol secretion, but did not observe any
      significant effects on reproductive parameters including birth weight. At 60 days
      of age, 48 daughters were randomly selected from the three treatments: half were
      challenged using a restraint and isolation test. Then, all were culled and brain
      tissue was collected. In situ hybridisation measurements showed increased
      expression of CRH mRNA in the PVN in unrestrained Mix 2 and in the amygdala of
      Mix 2 and Mix 3 daughters. At 67 days, 24 further daughters were mixed to measure
      their responses to this social stress. All showed increased salivary cortisol
      secretion, but Mix 2 and Mix 3 daughters showed a greater and longer response
      than controls. Finally, all 24 were inseminated and at parturition maternal
      behaviour was measured. Mix 2 and Mix 3 daughters were more restless and more
      responsive to piglets that approached the head of the sow, traits which
      previously have been shown to be a component of abnormal maternal behaviour.
      Indeed, Mix 2 and Mix 3 daughters also tended to bite at their piglets more than
      control daughters.

PMID- 15961090
TI  - Unrecognized peripartum cardiomyopathy in Haitian women.
AB  - OBJECTIVE: Haitian women have a high relative incidence of clinical presentation
      with peripartum cardiomyopathy (PPCM): an incidence estimated at one case per
      three hundred live births, a ten-fold occurrence compared to American women. Our
      objective has been to test the hypothesis that some Haitian women may have a
      forme fruste of PPCM while still without clinical symptoms. METHOD: A preliminary
      case-control study was conducted at the Hospital Albert Schweitzer (HAS),
      Deschapelles, Haiti, in which 25 apparently healthy postpartum women, without
      cardiovascular symptoms and with a normal cardiovascular clinical examination,
      were selected from a consecutive list of obstetrical deliveries and screened by
      echocardiography for left ventricular dysfunction. RESULT: Four out of 25
      patients (16%) had asymptomatic left ventricular dysfunction that subsequently
      evolved towards either improvement or deterioration. Supporting evidence for the
      existence of asymptomatic left ventricular dysfunction or forme fruste PPCM is
      presented. A hypothetical schema of the pathophysiology of PPCM explains how a
      latent phase of variable duration may exist prior to onset of detectable clinical
      heart failure. CONCLUSION: Screening Haitian women during the last month of
      pregnancy or in the early postpartum period may help to detect asymptomatic left
      ventricular dysfunction. Early detection and treatment of PPCM in a known high
      risk population could lead to improvements in maternal and fetal mortality and
      morbidity.

PMID- 15961091
TI  - Geriatric fear of falling measure: development and psychometric testing.
AB  - Development of the geriatric fear of falling measure (GFFM) was based on a
      previous qualitative study of Taiwanese community-dwelling elders. Relevant
      parameters or items for assessing subscales were identified and tested in a three
      stage process: item development, content validity testing and reliability
      testing. The GFFM was tested on two groups of community-dwelling elders in Taiwan
      (N=100 and 384) to examine validity and reliability. Good test-retest, internal
      consistency and inter-rater reliability were found. Confirmatory factor analysis
      and good overall model fits supported construct validity of the GFFM. Although
      these data are preliminary, the GFFM could be used as a quick screening
      instrument to evaluate fear of falling and an outcome indicator of nursing
      interventions.

PMID- 15961092
TI  - FEA analysis of silicone MCP implant.
AB  - This paper discusses finite element study of silicone rubber prosthesis for the
      metacarpophalangeal joint of the hand. Based on the experimental data, a material
      model which incorporates test data available for different stress states was
      chosen and calibrated. Finite element models for three commercially available
      silicone joint prosthesis were developed. All models incorporated the same
      material model and allowed for large deformations. These models were validated
      against the experimental data and analyzed under demanding loading conditions.
      Results such as highly non-linear material behavior, dependence on the loading
      history and large deformations near wrinkle formation in the hinge area of the
      joint clearly show the necessity and importance of using multi-stress- state non
      linear material models and accounting for large deformations.

PMID- 15961093
TI  - The effect of three-dimensional shape optimization on the probabilistic response
      of a cemented femoral hip prosthesis.
AB  - Probabilistic analyses allow the effect of uncertainty in system parameters on
      predicted model performance measures to be determined. Furthermore, using
      performance functions to describe a failure event, the probability of failure can
      be quantified. The effect of three-dimensional prosthesis shape optimization on
      the probabilistic response and failure probability of a cemented hip prosthesis
      system is investigated. Random variables include joint and muscle loading,
      cortical and cancellous bone and PMMA bone cement elastic properties, and
      strength parameters describing failure of the bone cement and the prosthesis-bone
      cement interface. Several performance functions describing the bone cement and
      prosthesis-cement interface are used to compute the probability of failure. When
      evaluated deterministically, most performance functions indicated a safe design,
      with the exception of interface tensile failure. However, when evaluated
      probabilistically, finite probabilities of failure were computed, some
      significant. The most likely mode of failure before shape optimization was
      prosthesis-bone cement interface tensile failure with a predicted probability of
      failure of 97.9%. Deterministic prosthesis shape optimization reduced the
      probability of failure for all performance functions and reduced prosthesis-bone
      cement interface tensile failure by 31.7%. Probability sensitivity factors
      indicate that the uncertainty in the joint loading, cement strength, and implant
      cement interface strength have the greatest effect on the computed probability of
      failure. Implant shape optimization results in a more robust implant design that
      is less sensitive to uncertainties in joint loading, which cannot be easily
      controlled, and more sensitive to cement and interface properties, which are
      easier to modify.

PMID- 15961094
TI  - Facile, alternative synthesis of lanthanum phosphate nanocrystals by
      ultrasonication.
AB  - Highly luminescent, rhabdophane (Ce(0.33)La(0.66))PO4.nH2O nanorods and
      nanoparticles were prepared in aqueous solutions by ultrasonication, at pH 1 and
      pH 12, respectively. Both nanorods (5 to 9 nm wide and several tens to several
      hundreds nm long) and nanoparticles (elongated, connected 5 nm particles) were as
      small and as uniform as products obtained from methods that utilize complexing
      agents or surfactants, only with no complexing agent. This method of synthesis by
      ultrasonication is a fast and simple method and it is expected to be applicable
      for the synthesis of other nanocrystalline lanthanide phosphates.

PMID- 15961095
TI  - Friction force measurements relevant to de-inking by means of atomic force
      microscope.
AB  - In the pulping step of the de-inking process, the ink detaches from the fibers
      due to shear and physical chemical interaction. In order to get a better
      understanding of the forces involved between cellulose and ink, the atomic force
      microscope and the colloidal probe technique have been used in the presence of a
      model chemical dispersant (hexa-ethyleneglycol mono n-dodecyl ether, C12E6). A
      cellulose bead was used as the colloidal probe and three different lower surfaces
      have been used, an alkyd resin, mica and a cellulose sphere. The normal and
      lateral forces have been measured at a range of nonionic concentrations. It was
      found that the lateral sliding friction forces deceased with increasing
      surfactant concentration for both the alkyd resin and mica while no differences
      were observed for the cellulose surface. In addition, only a very small change in
      normal force could be detected for the alkyd surface as the concentration
      changed.

PMID- 15961096
TI  - Sorption and immobilization of cellulase on silicate clay minerals.
AB  - The interaction of organic molecules with mineral surfaces is a subject of
      interest in a variety of disciplines. Enzymes are able to be sorbed and
      immobilized by clay minerals and humic colloids in soil environment. The present
      study was done to elucidate some aspects of sorption and immobilization of
      cellulase on soil components by analysis of the sorption, and immobilization of
      cellulase on Avicel, a soil sample, illite, kaolinite, montmorillonite, and
      palygorskite. Palygorskite displayed the highest sorption capacity. Sorbents
      coated with hydroxyaluminum displayed significantly higher capacity than uncoated
      sorbents. The positive effects of Al(OH)(x) coating on sorption capacities of the
      different sorbents were not equal. The effect decreased in the order soil >
      palygorskite > kaolinite > Avicel > montmorillonite > illite. The amount of
      sorbed cellulase desorbed from external surfaces of soil was quite low (about
      16%), especially in coated samples (about 6%). X-ray diffraction analysis of K
      montmorillonite and Ca-montmorillonite showed that Al(OH)(x) was intercalated
      between the montmorillonite layers. Immobilization of cellulase on the sorbents
      did not result in expansion of their crystal structures. Therefore, it may be
      concluded that the amount of cellulase immobilized on internal surfaces of the
      sorbents was negligible.

PMID- 15961098
TI  - Effect of urea on self-organization of sodium N-(11-acrylamidoundecanoyl)-L
      valinate in water.
AB  - In this paper, the hypotheses proposed for the action of urea on the perturbation
      of molecular assemblies have been tested through studies of the effects of urea
      on the aggregation properties of a chiral surfactant, sodium N-(11
      acrylamidoundecanoyl)-L-valinate in water. Surface tension, fluorescence, and
      circular dichroism were used to characterize the solution behavior of the
      amphiphile in the presence of urea. Surface tension measurement indicated
      decrease of critical aggregation concentration (cac) with the addition of urea in
      the low concentration range. Fluorescence probe studies using pyrene and 1
      anilinonaphthalene indicated solubilization of urea molecules near the aggregate
      water interface. Fluorescence anisotropy measurements using 1,6
      diphenylhexatriene as probe molecule suggested increase of packing of the
      hydrocarbon chains of the amphiphiles upon addition of low concentration of urea.
      Dynamic light scattering measurements showed an increase of the hydrodynamic
      radius (R(h)) in the presence of increased concentration of urea. At higher
      concentrations of urea, the R(h) value decreased. Circular dichroism spectra
      showed the presence of chiral aggregates even in the presence of high
      concentration of urea.

PMID- 15961099
TI  - Enhancement of the electrochemical properties of LiMn2O4 through Al3+ and F- co
      substitution.
AB  - The cathode-active materials LiMn2O4, LiAl0.1Mn1.9O4, and LiAl0.1Mn1.9O3.9F0.1
      were synthesized by a microwave-assisted sol-gel method. The influence of
      different doping elements on the structural and electrochemical properties of the
      as-prepared samples was investigated by thermogravimetric analysis (TGA), X-ray
      diffraction (XRD), transmission electron microscopy (TEM), and electrochemical
      experiments. The results indicated that fluorine plays an important role in
      controlling the morphology, and the doped aluminum could enhance significantly
      the stability of spinel-type LiMn2O4. The initial discharge capacity of the Al3+
      and F- co-substituted specimen reached 129.8 mA h/g and has a high capacity
      retention after 40 cycles. The outstanding electrochemical properties of
      LiAl0.1Mn1.9O3.9F0.1 make it a possible promising cathode material for lithium
      ion batteries.

PMID- 15961100
TI  - Studies on manganese nodule leached residues 2. Adsorption of aqueous phosphate
      on manganese nodule leached residues.
AB  - Adsorption of phosphate onto manganese nodule leached residues was investigated
      as a possible alternative to conventional methods of phosphate removal from
      industrial effluents. Adsorption behaviors were studied as a function of time,
      temperature, pH, and concentration level of adsorbate and adsorbent in acetic
      acid-sodium acetate buffer medium. The adsorption of phosphate follows the
      Langmuir adsorption isotherms. The magnitude of adsorption of phosphate in
      manganese nodule leached residues was compared with that in naturally occurring
      Mn nodule. Manganese nodule leached residues show better affinity toward
      phosphate adsorption.

PMID- 15961101
TI  - Structural basis for the thermostability of ferredoxin from the cyanobacterium
      Mastigocladus laminosus.
AB  - Plant-type ferredoxins (Fds) carry a single [2Fe-2S] cluster and serve as
      electron acceptors of photosystem I (PSI). The ferredoxin from the thermophilic
      cyanobacterium Mastigocladus laminosus displays optimal activity at 65 degrees C.
      In order to reveal the molecular factors that confer thermostability, the crystal
      structure of M.laminosus Fd (mFd) was determined to 1.25 A resolution and
      subsequently analyzed in comparison with four similar plant-type mesophilic
      ferredoxins. The topologies of the plant-type ferredoxins are similar, yet two
      structural determinants were identified that may account for differences in
      thermostability, a salt bridge network in the C-terminal region, and the flexible
      L1,2 loop that increases hydrophobic accessible surface area. These conclusions
      were verified by three mutations, i.e. substitution of L1,2 into a rigid beta
      turn ((Delta)L1,2) and two point mutations (E90S and E96S) that disrupt the salt
      bridge network at the C-terminal region. All three mutants have shown reduced
      electron transfer (ET) capabilities and [2Fe-2S] stability at high temperatures
      in comparison to the wild-type mFd. The results have also provided new insights
      into the involvement of the L1,2 loop in the Fd interactions with its electron
      donor, the PSI complex.

PMID- 15961102
TI  - Determining protein topology from skeletons of secondary structures.
AB  - We report a novel computational procedure for determining protein native
      topology, or fold, by defining loop connectivity based on skeletons of secondary
      structures that can usually be obtained from low to intermediate-resolution
      density maps. The procedure primarily involves a knowledge-based geometry filter
      followed by an energetics-based evaluation. It was tested on a large set of
      skeletons covering a wide range of protein architecture, including one modeled
      from an experimentally determined 7.6A cryo-electron microscopy (cryo-EM) density
      map. The results showed that the new procedure could effectively deduce protein
      folds without high-resolution structural data, a feature that could also be used
      to recognize native fold in structure prediction and to interpret data in fields
      like structure genomics. Most importantly, in the energetics-based evaluation, it
      was revealed that, despite the inevitable errors in the artificially constructed
      structures and limited accuracy of knowledge-based potential functions, the
      average energy of an ensemble of structures with slightly different
      configurations around the native skeleton is a much more robust parameter for
      marking native topology than the energy of individual structures in the ensemble.
      This result implies that, among all the possible topology candidates for a given
      skeleton, evolution has selected the native topology as the one that can
      accommodate the largest structural variations, not the one rigidly trapped in a
      deep, but narrow, conformational energy well.

PMID- 15961103
TI  - The three-dimensional structures of tick carboxypeptidase inhibitor in complex
      with A/B carboxypeptidases reveal a novel double-headed binding mode.
AB  - The tick carboxypeptidase inhibitor (TCI) is a proteinaceous inhibitor of metallo
      carboxypeptidases present in the blood-sucking tick Rhipicephalus bursa. The
      three-dimensional crystal structures of recombinant TCI bound to bovine
      carboxypeptidase A and to human carboxypeptidase B have been determined and
      refined at 1.7 A and at 2.0 A resolution, respectively. TCI consists of two
      domains that are structurally similar despite the low degree of sequence
      homology. The domains, each consisting of a short alpha-helix followed by a small
      twisted antiparallel beta-sheet, show a high level of structural homology to
      proteins of the beta-defensin-fold family. TCI anchors to the surface of
      mammalian carboxypeptidases in a double-headed manner not previously seen for
      carboxypeptidase inhibitors: the last three carboxy-terminal amino acid residues
      interact with the active site of the enzyme in a way that mimics substrate
      binding, and the N-terminal domain binds to an exosite distinct from the active
      site groove. The structures of these complexes should prove valuable in the
      applications of TCI as a thrombolytic drug and as a basis for the design of novel
      bivalent carboxypeptidase inhibitors.

PMID- 15961104
TI  - Inhibition of myotoxic activity of Bothrops asper myotoxin II by the anti
      trypanosomal drug suramin.
AB  - Suramin, a synthetic polysulfonated compound, developed initially for the
      treatment of African trypanosomiasis and onchocerciasis, is currently used for
      the treatment of several medically relevant disorders. Suramin, heparin, and
      other polyanions inhibit the myotoxic activity of Lys49 phospholipase A2
      analogues both in vitro and in vivo, and are thus of potential importance as
      therapeutic agents in the treatment of viperid snake bites. Due to its
      conformational flexibility around the single bonds that link the central phenyl
      rings to the secondary amide backbone, the symmetrical suramin molecule binds by
      an induced-fit mechanism complementing the hydrophobic surfaces of the dimer and
      adopts a novel conformation that lacks C2 symmetry in the dimeric crystal
      structure of the suramin-Bothrops asper myotoxin II complex. The simultaneous
      binding of suramin at the surfaces of the two monomers partially restricts access
      to the nominal active sites and significantly changes the overall charge of the
      interfacial recognition face of the protein, resulting in the inhibition of
      myotoxicity.

PMID- 15961105
TI  - Anterior resection of rectal cancer through a one hand-size incision with or
      without laparoscopy: proposal of one hand-size incision surgery (OHaSIS).
AB  - BACKGROUND: One hand-size incision surgery (OHaSIS) is a surgery that is carried
      out through one hand-size incision with or without laparoscopy. Safety,
      feasibility and recovery advantage of the anterior resection of rectal cancer by
      the OHaSIS were studied. STUDY DESIGN: Nineteen consecutive patients with rectal
      cancer, consisting of seven rectosigmoid, six upper rectal, and six lower rectal
      cancers, were treated with anterior resection, including seven high, six low,
      three super-low, and three partial intersphincteric resections, through a
      suprapubic longitudinal one hand-size incision. The initial 11 patients were
      treated in combination with laparoscopy and the following eight patients were
      treated without laparoscopy. RESULTS: All anterior resections with mesorectal
      excision were completed in a safe manner with acceptable operative time (average
      245 min), blood loss (average 280 g), and postoperative complications without any
      elongation of the initial incision. When compared with 12 previous high and low
      anterior resections by conventional open surgery (OS), the 13 high and low
      anterior resections by the OHaSIS showed equivalent operative time, blood loss,
      anastomotic procedures of single stapling, lymph node numbers dissected, surgical
      margin of the anal side of the tumor, and complications. Moreover, analysis of
      perioperative parameters for surgical invasiveness, including a body temperature
      >37 degrees C, days of bed rest, and days of use of parenteral narcotics,
      revealed a recovery advantage in the OHaSIS group compared with that in the OS
      group. CONCLUSIONS: These results suggest that anterior resection for patients
      with rectal cancer by the OHaSIS is safe, feasible, and less invasive than
      conventional OS, and has sufficient operative performance. Although the survival
      benefit and recurrence rate by this approach must be ensured in a future trial,
      we would like to propose the new concept of OHaSIS for treating rectal cancer.

PMID- 15961106
TI  - Nitric oxide and skeletal muscle reperfusion injury: current controversies
      (research review).
AB  - Nitric oxide (NO) has been implicated in a large number of disease processes,
      including ischemia-reperfusion injury following the restoration of oxygenated
      blood to previously ischemic muscle, which is a recognized significant
      complication of vascular surgery. Altered metabolism of NO is implicated in the
      endothelial dysfunction that forms part of the pathophysiology of ischemia
      reperfusion injury. However, NO can demonstrate either protective or cytotoxic
      effects during reperfusion injury. The use of transgenic mice, either NO synthase
      (NOS) gene knockout animals, or animals that over-express NOS isoforms, along
      with direct NO measurements and NO donor or inhibitor studies, have all
      demonstrated a role for NO in skeletal muscle reperfusion injury. There appears
      to be an initial stimulation of NO production in the first 20-min of ischemia,
      with a gradual decline through early reperfusion and a second higher peak of NO
      commencing in the later stages of reperfusion. The absolute levels of NO in the
      reperfused tissue and its regulation by the subtle interplay with superoxide and
      the subsequent production of the highly toxic peroxynitrite anion, are important
      factors in determining whether NO, in the context of ischemia-reperfusion injury,
      has damaging or protective effects in the body.

PMID- 15961107
TI  - A prospective uncontrolled trial of fermented milk drink containing viable
      Lactobacillus casei strain Shirota in the treatment of HTLV-1 associated
      myelopathy/tropical spastic paraparesis.
AB  - Ten patients with human T-cell lymphotropic virus type-1 (HTLV-1)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) were treated in an uncontrolled
      preliminary trial by oral administration of viable Lactobacillus casei strain
      Shirota (LcS) containing fermented milk. HTLV-1 provirus load, motor function,
      neurological findings, and immunological parameters were evaluated after 4 weeks.
      Although LcS did not change the frequencies or absolute numbers of all the
      examined cell surface phenotypes of peripheral blood mononuclear cells, NK cell
      activity was significantly increased after 4 weeks of oral administration of LcS
      preparation. Improvements in spasticity (modified Ashworth Scale scores) and
      urinary symptoms were also seen after LcS treatment. No adverse effect was
      observed in all the 10 patients throughout the study period. Our results
      indicated that LcS may be a safe and beneficial agent for the treatment of
      HAM/TSP; therefore randomized controlled studies are warranted.

PMID- 15961108
TI  - Hypo-excitability of cortical areas in patients affected by Friedreich ataxia: a
      TMS study.
AB  - The aim of the study was to explore excitability of a motor and a non-motor
      (visual) area in patients affected by Friedreich ataxia and to correlate
      neurophysiological data with clinical parameters. Seven patients (3M/4F) and ten
      healthy controls (5M/5F) participated in the study. The hot-spot for activation
      of right abductor pollicis brevis was checked by means of a figure-of-eight coil
      and the motor threshold (MT) on this point was recorded. The phosphene threshold
      (PT) was measured by means of a focal coil over the occipital cortex as the lower
      intensity of magnetic stimulation able to induce the perception of phosphenes.
      The patients showed a significantly higher mean PT (p<.03) and MT values (p<.001)
      than controls. In all but one patient unable to perceive phosphenes (42% vs. 50%
      of controls), TMS at 100% intensity did not elicit motor response at rest. The
      difference in percentage of patients (57.1%) and controls (100%) with motor
      responses was nearly significant. The size of GAA1 expansion showed significant
      correlations with PT and MT values. The results of our study showed that FA
      patients had reduced cortical activation, involving both the motor and the visual
      cortex. The cortical involvement in these patients seems to be mainly genetically
      determined. The study provides the first evidence of cortical dysfunction in
      patients with genetically defined Friedreich ataxia.

PMID- 15961109
TI  - Inflammatory response after acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: This study aimed to characterize the time course of
      inflammatory parameters after acute ischemic stroke. METHODS: We serially
      determined high sensitivity C-reactive protein (CRP), fibrinogen, and leukocyte
      counts at 10 time points between days 1 and 90 after ischemic stroke and in
      control subjects. RESULTS: CRP did not significantly change, whereas fibrinogen
      increased after stroke. At all time points, CRP and fibrinogen were higher than
      in healthy control subjects, but not risk factor control subjects. The leukocyte
      count declined after stroke and was significantly elevated as compared to both
      control groups only on day 1 but not later. NIHSS levels were positively
      correlated with CRP and fibrinogen at all time points. Larger infarcts were
      associated with a higher CRP and leukocyte counts on day 90. Treatment with
      aspirin was associated with lower values for all three inflammatory parameters in
      the subacute phase after ischemia. CONCLUSIONS: The course after stroke was
      different between the parameters of inflammation. Only the leukocytes followed
      the paradigm of an acute phase response.

PMID- 15961110
TI  - Neuroimaging as a marker of the onset and progression of Alzheimer's disease.
AB  - Several neuroimaging techniques are promising tools as early markers of brain
      pathology in Alzheimer's disease (AD). On structural MRI, atrophy of the
      entorhinal cortex is present already in mild cognitive impairment (MCI). In the
      autosomal dominant forms of AD, the rate of atrophy of medial temporal structures
      separates affected from control persons even 3 years before the clinical onset of
      cognitive impairment. The elevated annual rate of brain atrophy offers a
      surrogate tool for the evaluation of newer therapies using smaller samples,
      thereby saving time and resources. On functional MRI, activation paradigms
      activate a larger area of parieto-temporal association cortex in persons at
      higher risk for AD, whereas the entorhinal cortex activation is lesser in MCI.
      Similar findings have been detected with activation procedures and water
      (H(2)(15)O) PET. Regional metabolism in the entorhinal cortex, studied with FDG
      PET, seems to predict normal elderly who will deteriorate to MCI or AD. SPECT
      shows decreased regional perfusion in limbic areas, both in MCI and AD, but with
      a lower likelihood ratio than PET. Newer PET compounds allow for the
      determination in AD of microglial activation, regional deposition of amyloid and
      the evaluation of enzymatic activity in the brain of AD patients.

PMID- 15961111
TI  - MEP recruitment curves in multiple sclerosis and hereditary spastic paraplegia.
AB  - OBJECTIVE: Axons remodel at multiple levels after a single inflammatory lesion in
      the spinal cord, which can contribute to recovery. The primary aim of this study
      was to investigate whether the MEP response as function of the excitatory
      strength, here called recruitment curves, may be used in discriminating
      demyelination from compensated axonal loss. Multiple sclerosis (MS) represents
      both demyelination and axonal degeneration. Hereditary Spastic Paraplegia (HSP)
      was included as a model of pure axonal loss. METHODS: To investigate both spinal
      and cortical recruitment, the methods used for gradual recruitment were two
      different test paradigms of voluntary pre-activation and stimulus intensity. The
      MEP-recruitment curves were obtained by means of transcranial magnetic
      stimulation (TMS) in 29 MS patients, 9 patients with HSP and in 30 healthy
      controls. RESULTS: Saturated recruitment curves were obtained in all subject
      groups, muscles and paradigms and were generally found to be identical. The two
      groups of patients had clinical signs, CMCT changes and reduced MEP amplitude
      reflecting relevant cortico-spinal disorder. CONCLUSIONS: We conclude that both
      demyelination and axonal degeneration in the CNS leads to diminished MEP
      amplitudes and CMCT changes. The recruitment curves of MS and HSP was identical
      to controls and may not be used for diagnostic or monitoring purposes.

PMID- 15961112
TI  - Approaching an individual methotrexate regimen in leptomeningeal carcinomatosis.
AB  - BACKGROUND: Chemotherapeutic effects in leptomeningeal carcinomatosis (LC) vary
      widely between patients, presumably in part because drug elimination from
      cerebrospinal fluid (CSF) differs between individuals. An individual dosing,
      adapted to elimination, may improve treatment efficacy. OBJECTIVE: To discuss the
      feasibility of easily accessible elimination parameters for an individual dosing
      of chemotherapy in LC. MATERIALS AND METHODS: The elimination of intrathecally
      applied methotrexate (Mtx) was tested in 14 LC patients and compared to the
      literature data. Plasma drug levels and CSF albumin levels are suggested as
      elimination parameters. RESULTS AND DISCUSSION: Mtx disappeared from CSF and
      appeared in plasma with an expected wide variation (interindividual range of
      coefficients of variation (CV) of CSF Mtx levels 158-189%, intraindividual range
      of CV of plasma Mtx levels 35-64%). Our data together with reported data suggest
      that plasma Mtx levels mirror closely the Mtx elimination from CSF. The levels of
      CSF albumin and of plasma Mtx at defined sample times correlated negatively (r=
      0.7), which reflects their largely common elimination from CSF. CONCLUSION: Both
      parameters seem appropriate to describe the Mtx elimination from CSF. They should
      allow to individually adapt Mtx dosing towards an improvement of Mtx availability
      in CSF and of treatment efficacy.

PMID- 15961113
TI  - Scaling phloem transport: elasticity and pressure-concentration waves.
AB  - Earlier theoretical analyses of the rate of propagation of pressure-concentration
      waves in the phloem were performed without adequate attention to the elastic
      expansion of sieve tube walls. Here, it is shown that the rate of propagation of
      pressure-concentration waves in phloem sieve tubes is not significantly impeded
      by wall elasticity, but rather, as previously implicated, by the ratio of sap
      osmotic pressure to the axial drop in sap hydrostatic pressure. It is also shown
      that pressure-concentration waves move equally well in both the upstream and
      downstream directions. These results permit future models to ignore elastic
      effects, and lend additional theoretical support to the "osmoregulatory flow"
      hypothesis, which argues that efficient molecular control of the phloem is
      permitted by maintaining sieve sap hydrostatic pressure at a value that is
      spatially nearly constant, which in turn permits changes in sieve tube state to
      be rapidly transmitted throughout the sieve tube via pressure-concentration
      waves.

PMID- 15961114
TI  - A collisional model of the energetic cost of support work qualitatively explains
      leg sequencing in walking and galloping, pseudo-elastic leg behavior in running
      and the walk-to-run transition.
AB  - Terrestrial legged locomotion requires repeated support forces to redirect the
      body's vertical velocity component from down to up. We assume that the
      redirection is accomplished by impulsive leg forces that cause small-angle
      glancing collisions of a point-mass model of the animal. We estimate the
      energetic costs of these collisions by assuming a metabolic cost proportional to
      positive muscle work involved in generating the impulses. The cost of bipedal
      running estimated from this collisional model becomes less than that of walking
      at a Froude number (v2/gl) of about 0.7. Two strategies to reduce locomotion
      costs associated with the motion redirection are: (1) having legs simulate purely
      elastic springs, as is observed in human running; and (2) sequencing the leg
      forces during the redirection phase; examples of this sequencing are the ba-da
      dump pattern of a horse gallop and having push-off followed by heel-strike in
      human walking.

PMID- 15961115
TI  - A density-based approach for the modelling of root architecture: application to
      Maritime pine (Pinus pinaster Ait.) root systems.
AB  - Root morphology influences strongly plant/soil interactions. However, the
      complexity of root architecture is a major barrier when analysing many phenomena,
      e.g. anchorage, water or nutrient uptake. Therefore, we have developed a new
      approach for the representation and modelling of root architecture based on
      branching density. A general root branching density in a space of finite
      dimension was used and enabled us to consider various morphological properties. A
      root system model was then constructed which minimizes the difference between
      measured and simulated root systems, expressed with functions which map root
      density in the soil. The model was tested in 2D using data from Maritime pine
      Pinus pinaster Ait. structural roots as input. We showed that simulated and real
      root systems had similar root distributions in terms of radial distance, depth,
      branching angle and branching order. These results indicate that general density
      functions are not only a powerful basis for constructing models of architecture,
      but can also be used to represent such structures when considering root/soil
      interaction. These models are particularly useful in that they provide a local
      morphological characterization which is aggregated in a given unit of soil
      volume.

PMID- 15961116
TI  - Lipidomics, drugs of abuse and NIDA.

PMID- 15961117
TI  - The action of PKA on smooth muscle myosin phosphorylation.
AB  - The aim of the study is to reveal the characterization of PKA acting on myosin.
      We found: (a) in the absence of Ca(2+)/CaM, PKA slightly phosphorylated MLC(20)
      and stimulated the Mg(2+)-ATPase activity of myosin, which was strengthened
      significantly by arachidonic acid (ACAD); (b) Ca(2+)-independent phosphorylation
      of myosin by PKA was obviously less efficient than both Ca(2+)-dependent and
      independent phosphorylation of myosin by MLCK; (c) micro-amount of calponin could
      not increase the precipitation of myosin phosphorylated by PKA, but it increased
      the precipitation of myosin phosphorylated by MLCK, suggesting the presence of
      conformational differences between the myosins phosphorylated by PKA and by MLCK.

PMID- 15961118
TI  - Toxicity to early life stages and an estrogenic effect of a bisphenol A
      metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on the medaka (Oryzias
      latipes).
AB  - In a recent study, it was reported that 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1
      ene (MBP), a metabolite of bisphenol A (BPA; 2,2-bis(4-hydroxyphenyl)propane),
      showed estrogenic activity in several in vitro assays, and the estrogenic
      activity of MBP was higher than that of BPA. In this study, we have investigated
      the early life stage toxicity and estrogenic effect of MBP on medaka (Oryzias
      latipes). The 96-h median lethal concentration value of MBP and BPA with 24-h-old
      larvae was estimated to be 1,640 and 13,900 microg/l, respectively. The
      hatchability of fertilized eggs exposed to MBP and BPA over 14 days was
      significantly decreased at doses of 2,500 microg/l and 12,500 microg/l,
      respectively. Moreover, to compare the potency of estrogenic activity in vivo,
      male medaka were exposed to various concentrations of MBP and BPA for 21 days.
      The lowest-observed-effect concentrations of MBP and BPA for hepatic vitellogenin
      induction in male medaka were estimated to be 4.1 and 1,000 microg/l,
      respectively. These results suggest that MBP has high toxicity for early life
      stages of the medaka, and that the estrogenic activity of MBP was about 250-fold
      higher than that of BPA to male medaka.

PMID- 15961120
TI  - Differential effects of sublethal ischemia and chemical preconditioning with 3
      nitropropionic acid on protein expression in gerbil hippocampus.
AB  - Pretreatment with a low dose of 3-nitropropionic acid (3-NPA) has been shown to
      induce ischemic tolerance in the gerbil hippocampus. It is well known that
      sublethal (2-min) ischemia also induces ischemic tolerance. To investigate the
      acquisition of ischemic tolerance with 3-NPA, we examined the protein expression
      after 3-NPA treatment in comparison with sublethal ischemia. Immunohistochemical
      studies revealed intense expression of Bcl-2 and Bcl-xL in the hippocampal CA1
      area after 3-NPA treatment. Furthermore, the time course of the expression of Bcl
      xL showed a similar pattern to the acquisition of ischemic tolerance by 3-NPA
      treatment. The induction of Bcl-xL occurred in the hippocampal CA1 area at 24 h
      after 3-NPA treatment, and significant induction was observed at 48 h. Western
      blot analysis of hippocampus harvested 48 h after the pretreatment, showed that
      the expression of Bcl-2 and Bcl-xL was significantly increased by either 3-NPA
      treatment or 2-min ischemia. However, PMCA1 and HSP70 protein expression
      increased only in the sublethal ischemia treated group. The difference between 3
      NPA treated group and control group was not statistically significant. These
      results suggest that Bcl-2 and Bcl-xL are essential for acquisition of ischemic
      tolerance, while HSP70 and PMCA1 play important roles in the enhancement of
      ischemic tolerance.

PMID- 15961121
TI  - Adriatic coast as a microcosm for global genotoxic marine contamination--a long
      term field study.
AB  - Global changes in the marine environment and the continuing disposal of genotoxic
      xenobiotics are increasing the importance of environmental pollution monitoring
      and of biomonitoring programs. Current approaches focus on investigations at
      regional and local levels in an attempt to precisely define the nature and extent
      of any potential environmental crisis. We have initiated, for the first time, a
      long-term biomonitoring program focusing on the Croatian coast of the Adriatic
      Sea to contribute to a more detailed understanding of marine genotoxic effects
      using the mussels Mytilus galloprovincialis Lam., collected along the eastern
      Adriatic coast over a period of five years (1998-2002), as a key test organism.
      The integrity of DNA in its gill homogenate was examined by the Fast Micromethod.
      The strand scission factor (SSF) values, as a measure of DNA integrity, DNA
      damage or incomplete repair have been used for the ranking of sampling sites with
      respect to significant genotoxic stress due to the influence or effects of
      genotoxic xenobiotics. The region of Split (Kastela Bay) proved to be the area
      with the heaviest load of genotoxic agents. The investigation of harmful effects
      in the ecosystem based on biomonitoring of genetic and other agents, not only on
      local levels but also on a wider scale, is considered as an important step in
      marine environmental management.

PMID- 15961122
TI  - Hydrocarbons in surface sediments from the Sfax coastal zone, (Tunisia)
      Mediterranean Sea.
AB  - The Semi-enclosed Mediterranean Sea records various signals of high anthropic
      pressures from surrounding countries and the industrialized European countries.
      This is particularly true for oil pollution. Although accounting for 1% of the
      world's ocean surface, it receives about 25% of the petroleum inputs to the
      ocean. To achieve a global budget we need to collect information from different
      parts of the Mediterranean. Particularly, we focus in this paper on the Southern
      Mediterranean, where data are presently very scarce. In this context, the
      University of Sfax has undertaken an estimation of hydrocarbon pollution along
      the coasts of Sfax and Gabes Gulf. Non-aromatic hydrocarbons were analysed in 8
      surface sediments by FT/IR and GC/MS. Non-aromatic hydrocarbon concentrations
      vary in the range 310-1406 microg g(-1) sediments dry weight, which is high,
      compared to other Mediterranean sites. GC/MS data indicate a large group of
      unresolved compounds suggesting a petroleum contamination, confirmed by the
      identification of hopanes with predominant C29 and C30alpha,beta compounds and
      steranes with predominance of C27 over C28) and C29 compounds.

PMID- 15961123
TI  - Reminiscences of a long-time colleague and friend, Philip C. Hanawalt.
AB  - Philip Hanawalt is a long time contributor to many areas of the DNA repair field.
      This article summarizes aspect of his relationship with the author over the past
      36 years.

PMID- 15961124
TI  - A bacterial model for studying effects of human mutations in vivo: Escherichia
      coli strains mimicking a common polymorphism in the human MTHFR gene.
AB  - A simple bacterial model for studying effects of human mutations in vivo, when
      homologous genes exist in bacterial and human cells, is presented. We have
      constructed Escherichia coli strains bearing different alleles of the metF gene,
      an ortologue of human MTHFR gene, coding for 5,10-methylenetetrahydrofolate
      reductase. These strains bear a null mutation in the chromosomal metF gene and
      different metF alleles on plasmid(s), and thus there are merozygotes mimicking
      wild-type homozygotes, heterozygotes and recessive mutant homozygotes. The A177V
      mutantion in metF corresponds to one of the most common MTHFR polymorphism,
      A222V, which has been shown to be associated with increased levels of
      homocysteine in plasma that, in turn, causes many serious medical problems.
      Results of relatively simple and quick experiments with these strains are
      compatible with previously published reports on effects of the A222V substitution
      in the product of MTHFR gene. In addition, these results suggest either
      impairment of formation of heterodimers and/or heterotetramers by wild-type and
      A177V metF variants or dominance of the wild-type polypepides in such structures.
      Moreover, positive effects of folic acid and vitamins B2 and B12 on physiology of
      the mutant cells, suggested on the basis of clinical studies, is confirmed.
      Therefore, we conclude that the bacterial model described in this report may be a
      useful tool in studies on human mutations.

PMID- 15961125
TI  - Evaluation of the role of P-glycoprotein in the uptake of paroxetine, clozapine,
      phenytoin and carbamazapine by bovine retinal endothelial cells.
AB  - Expression of the drug transport proteins, including P-glycoprotein (Pgp), in the
      brain vascular endothelium represents a challenge for the effective delivery of
      drugs for the treatment of several central nervous system (CNS) disorders
      including depression, schizophrenia and epilepsy. It has been hypothesized that
      Pgp plays a major role in drug efflux at the blood-brain barrier, and may be an
      underlying factor in the variable responses of patients to CNS drugs. However,
      the role of Pgp in the transport of many CNS drugs has not been directly
      demonstrated. To explore the role of Pgp in drug transport across an endothelial
      cell barrier derived from the central nervous system, the expression and activity
      of Pgp in bovine retinal endothelial cells (BRECs) and the effects of
      representative CNS drugs on Pgp activity were examined. Significant Pgp
      expression in BRECs was demonstrated by western analyses, and expression was
      increased by treatment of the cells with hydrocortisone. Intracellular
      accumulation of the well-characterized Pgp-substrate Taxol was markedly increased
      by the non-selective transporter inhibitor verapamil and the Pgp-selective
      antagonist PGP-4008, demonstrating that Pgp is active in these endothelial cells.
      In contrast, neither verapamil nor PGP-4008 affected the intracellular
      accumulation of [3H]paroxetine, [14C]phenytoin, [3H]clozapine or
      [14C]carbamazapine, indicating that these drugs are not substrates for Pgp.
      Paroxetine, clozapine and phenytoin were shown to be Pgp inhibitors, while
      carbamazapine did not inhibit Pgp at any concentration tested. These results
      indicate that Pgp is not likely to modulate patient responses to these drugs.

PMID- 15961126
TI  - Lack of stimulant and anxiolytic-like effects of ethanol and accelerated
      development of ethanol dependence in mu-opioid receptor knockout mice.
AB  - The opioid system is implicated in various aspects of alcoholism. Acute ethanol
      administration produces anxiolytic-like effects in rodents while alcohol
      withdrawal induces anxiogenic-like effects. Mice lacking the mu-opioid receptor
      (MOR) do not self-administer ethanol and display decreased anxiety-like behavior.
      We hypothesized that MOR might be involved in the development and expression of
      alcoholism, particularly in relation to anxiety states. In mice lacking MOR (MOR
      /- mice), we examined the acute anxiolytic-like and locomotor stimulant effects
      of ethanol (0, 0.75, 1.25, 1.75 g/kg, i.p.). In a separate experiment, mice were
      submitted to chronic ethanol-containing liquid diet and we assessed somatic and
      affective ethanol withdrawal on three consecutive withdrawal episodes by scoring
      handling-induced convulsions and anxiety-like behavior. Deletion of MOR blocked
      the acute anxiolytic-like and stimulant effects of ethanol. Furthermore, MOR-/-
      mice displayed affective and physical signs of ethanol withdrawal in earlier
      withdrawal tests than wild-type mice. The present results implicate MOR in
      affective and somatic aspects of ethanol exposure and withdrawal. In addition,
      our findings support the hypothesis that the clinical efficacy of the opioid
      receptor antagonist naltrexone against relapse to alcoholism might be related to
      an action on the acute positive effects of alcohol rather than the negative
      affect of abstinence.

PMID- 15961127
TI  - Alterations in GABAA receptor occupancy occur during the postnatal development of
      rat Purkinje cell but not granule cell synapses.
AB  - The identification of synaptic GABA(A) receptors has proved difficult as neurones
      express multiple GABA(A) receptor subunits. For example, cerebellar granule cells
      express alpha1, alpha6, gamma2, delta and beta2/3 subunits and thus express many
      different GABA(A) receptor subtypes. Furthermore, the contribution of individual
      GABA(A) receptor subtypes is changed by developmental alterations in subunit
      expression. To further characterise the pharmacology of Golgi cell to granule
      cell synapses during development, the benzodiazepine-site ligand zolpidem was
      used. Zolpidem shows selectivity for alpha1betaxgamma2 receptors (x is any beta
      subunit) and slows the decay and enhances the amplitude of alpha1betaxgamma2
      receptor-mediated synaptic currents, provided the receptors are not fully
      occupied. For comparison, zolpidem was applied to Purkinje cell synapses, since
      the synaptic receptors are of known composition (alpha1betaxgamma2). At immature
      and adult Golgi cell to granule cell synapses, the decay of spontaneous and
      miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) was slowed by
      zolpidem but their amplitude and frequency were unaffected. At Purkinje cell
      synapses, although zolpidem slowed the decay of IPSCs at both immature and adult
      synapses, zolpidem only enhanced the amplitude of IPSCs at adult synapses. Thus
      during development, the level of receptor occupation remains constant at Golgi
      cell to granule cell synapses but falls at Purkinje cell synapses.

PMID- 15961128
TI  - Proximal cues of pocket gopher burrow plugging behavior: influence of light,
      burrow openings, and temperature.
AB  - Burrow plugging is readily observed among mammals adapted for digging (i.e.,
      fossorial mammals) as they create and maintain their burrows. We investigated the
      influence of light, burrow openings, and thermal environment as cues of pocket
      gopher (Thomomys mazama, Thomomys talpoides) behavior. When given free access to
      light and no light during artificial-burrow preference trials, both Thomomys spp.
      consistently plugged (i.e., avoided) light treatments. Burrow openings did not
      notably affect plugging behavior of T. mazama. Gophers (T. talpoides) plugged the
      artificial burrows within the light and cold (7 degrees C) treatments, but not
      within the no-light, and 18 or 31 degrees C treatments when light and temperature
      were varied independently. Whereas the presence of light and low ambient
      temperatures induce burrow maintenance by pocket gophers, these cues help
      meliorate adverse conditions within subsurface environs.

PMID- 15961129
TI  - A battery of olfactory-based screens for phenotyping the social and sexual
      behaviors of mice.
AB  - We provide a battery of screens that reflect the social and sexual behavior
      displayed by both captive and feral mice. Some screens focus on measuring aspects
      of chemical communication, providing information about whether or not mice will
      interact and if they do so, predict the nature of the interaction. Other screens
      measure direct interactions between target mice and same- and opposite-sex
      conspecifics, providing an indication of the social status and sexual
      responsiveness, respectively, of target mice. The battery of screens yields a
      high-throughput bioassay of a mouse's relative social status, competitive
      ability, social discrimination, and sexuality. These traits are essential
      elements of the socio-sexual behavior of mice as well as humans. Thus, by
      identifying phenotypic deviants for complex behaviors we will allow geneticists
      to map behavioral abnormalities onto specific chromosomes and increase the
      efficacy of genetically altered mice as models for human behavioral disorders.

PMID- 15961130
TI  - Clinical and pathological features of experimental scrapie in Irish Blackface
      Mountain sheep.
AB  - There have been no reports of natural scrapie in Irish Blackface Mountain (BM)
      sheep which account for approximately 16% of the Irish national sheep flock. The
      aim of this study was to determine if Irish BM sheep had unusual clinical and/or
      pathological features of scrapie which would account for failure to diagnose the
      disease in this breed. BM (n=7), Texel (n=3) and Suffolk sheep (n=1) of scrapie
      susceptible PrP genotypes (ARQ/ARQ and VRQ/ARQ) were orally challenged with
      scrapie-infected brain inoculum. The incubation period, clinical signs, pathology
      and distribution of disease specific prion protein (PrP(d)) in scrapie-affected
      BM sheep were similar to scrapie in the Texel and Suffolk sheep. It was concluded
      that there was no evidence to suggest that scrapie in BM sheep differs
      clinicopathologically from scrapie in other breeds of sheep.

PMID- 15961131
TI  - Hormesis is not homeopathy.

PMID- 15961133
TI  - Flow acoustics in periodic structures.
AB  - A recent paper [A.A. Krokhin, J. Arriaga, L.N. Gumen, Speed of sound in periodic
      elastic composites, Phys. Rev. Lett. 91 (2004) 264302-1-4] addresses the speed of
      sound in periodic elastic composites (phononic crystals) with particular emphasis
      to the case where air bubbles are present in water and arranged periodically. In
      such periodically arranged mixtures, the well-known phenomena of the drop of the
      speed of sound may occur and applications related to, e.g., sound-beam focusing
      and acoustic surgery are possible [F. Cervera, L. Sanchez, J.V. Sanchez-Perez, R.
      Martinez-Sala, C. Rubio, F. Meseguer, C. Lopez, D. Caballero, J. Sanchez-Dehesa,
      Phys. Rev. Lett. 88 (2002) 023902]. In this paper, the analysis is extended
      theoretically to include cases where a background flow in a periodic structure is
      maintained. Calculations of dispersion relations and group velocities are
      presented in cases with one- and two-dimensional material periodicity for
      background flow values in the range: 0-1m/s. Materials considered in the
      calculations are periodic water-air mixtures. It is shown that acoustic waves
      couple to the group velocities only if the (acoustic) wave vector has a component
      along the background flow velocity direction.

PMID- 15961134
TI  - A nuclear localization signal in the matrix of spleen necrosis virus (SNV) does
      not allow efficient gene transfer into quiescent cells with SNV-derived vectors.
AB  - A major limitation in gene therapy for vectors derived from Moloney murine
      leukemia virus (MLV) is that they only deliver genes into dividing cells. In this
      study, a careful comparison of spleen necrosis virus (SNV)-derived vectors with
      MLV and human immunodeficiency virus (HIV)-1 retroviral vectors indicated that
      SNV vectors can deliver genes 4-fold more efficiently than MLV vectors into
      aphidicolin-arrested cells, although at a 25-fold lower efficiency than HIV-1
      derived vectors. Furthermore, the addition of a NLS in the SNV matrix (MA) that
      mimics the one located in HIV-1 MA did not increase the ability of SNV vectors to
      transfer genes into arrested cells. Also, we found that the RD114 envelope was
      able to pseudotype SNV viral particles in a very efficient manner.

PMID- 15961135
TI  - CD4 T cell control of acute and latent murine gammaherpesvirus infection requires
      IFNgamma.
AB  - Murine gammaherpesvirus 68 (gammaHV68, MHV-68)-specific CD4 T cells control
      gammaHV68 infection by reducing the frequency of latently infected cells and by
      inhibiting viral replication. We have previously demonstrated that CD4 T cells do
      not require CD8 T or B cells to control gammaHV68 replication, demonstrating a
      helper-independent activity of CD4 T cells during gammaHV68 infection. The
      effector mechanism(s) required for this helper-independent function of CD4 T
      cells and for the inhibition of the establishment of latency by CD4 T cells are
      not known. Since IFNgamma has been previously shown to be important for control
      of acute, latent, and persistent gammaHV68 infection, we tested the hypothesis
      that CD4 T cells require IFNgamma to limit gammaHV68 latency and replication. We
      utilized a previously described system in which T cell receptor (TCR) transgenic
      T cells (DO.11.10) and a recombinant virus (gammaHV68.OVA) allow for evaluation
      of high numbers of virus-specific CD4 T cells during both acute and latent
      infection. We show here that virus-specific CD4 T cells require IFNgamma for
      their anti-viral function in both acute and latent gammaHV68 infection. We
      additionally show that an in vitro derived T helper type 1 (TH1) CD4 T cell
      clone, which produces IFNgamma, inhibits gammaHV68 replication after adoptive
      transfer into RAG mice. Together, data presented here demonstrate that both CD4 T
      cell-mediated helper-independent control of gammaHV68 replication and inhibition
      of the establishment of gammaHV68 latency require IFNgamma.

PMID- 15961137
TI  - Perception of depth and motion from ambiguous binocular information.
AB  - The visual system can determine motion and depth from ambiguous information
      contained in images projected onto both retinas over space and time. The key to
      the way the system overcomes such ambiguity lies in dependency among multiple
      cues--such as spatial displacement over time, binocular disparity, and
      interocular time delay--which might be established based on prior knowledge or
      experience, and stored in spatiotemporal response characteristics of neurons at
      an early cortical stage. We conducted a psychophysical investigation of whether a
      single ambiguous cue (specifically, interocular time delay) permits depth
      discrimination and motion perception. Data from this investigation are consistent
      with the predictions derived from the response profiles of V1 neurons, which show
      interdependency in their responses to each cue, indicating that spatial and
      temporal information is jointly encoded in early vision.

PMID- 15961136
TI  - Liver injury and viremia in mice infected with dengue-2 virus.
AB  - The goal of this study was to test the feasibility of BALB/c mice as an
      experimental model in the study of dengue disease. BALB/c mice were
      intraperitoneal infected with DENV-2 obtained from a human patient.
      Histopathological analysis of infected animals revealed liver injury with viral
      antigens detection. In initial stages, the most prominent lesions were
      vacuolization and diffuse steatosis in hepatocytes. Serum levels of ALT and AST
      increased progressively, reaching the highest values 7 days p.i. and decreasing
      at the 14th day. Since levels of circulating virus were very low, viremia was
      analyzed in C6/36 cells. Virus presence was detected by ultrastructural analysis,
      confirmed by RT-PCR assays. Period of viremia was analyzed by flow cytometry with
      cells incubated with mouse-infected sera collected in different days, revealing
      peak virus levels at the 7th day p.i. All such data correlate to the development
      of the disease described in humans.

PMID- 15961138
TI  - Acceleration of tributyltin chloride (TBT) degradation in liquid cultures of the
      filamentous fungus Cunninghamella elegans.
AB  - In this study, we have examined the effects of synthetic medium ingredients and
      culture incubation conditions on growth and tributyltin chloride (TBT)
      degradation activity of the fungus Cunninghamella elegans. The best efficiency of
      TBT conversion to less toxic derivatives: dibutyltin and monobutyltin was noticed
      on media which contained glucose, NH(4)Cl, K(2)HPO(4) and MgSO(4). Next, the
      constructed M3 medium (with the above components) ensured vigorous growth of C.
      elegans and allowed the reduction of 80% of the initial TBT content (10 mg l(
      1)), after 3d of biodegradation. The further acceleration of the biocide
      utilization by C. elegans was achieved by additional oxygen supply (pO(2) >or =
      20%) to the growing fungus (89% after 2d of incubation in the BioFlo II
      bioreactor). The efficient xenobiotic biodegradation was related to the intensity
      of fungal growth. The obtained results suggest a cometabolic nature of TBT
      utilization by C. elegans.

PMID- 15961139
TI  - Effect of VOC loading on the ozone removal efficiency of activated carbon
      filters.
AB  - Activated carbon (AC) filters are used widely in air cleaning to remove volatile
      organic compounds (VOCs) and ozone (O(3)). This paper investigates the O(3)
      removal efficiency of AC filters after previous exposure to VOCs. Filter
      performance was tested using coconut shell AC and two common indoor VOCs, toluene
      and d-limonene, representing low and high reactivities with O(3). AC dosed with
      low, medium and high loadings (28-100% of capacity) of VOCs were exposed to
      humidified and ozonated air. O(3) breakthrough curves were measured, from which
      O(3) removal capacity and parameters of the Elovich chemisorption equation were
      determined. VOC-loaded filters were less efficient at removing O(3) and had
      different breakthrough behavior than unloaded filters. After 80 h of exposure,
      VOC-loaded AC samples exhibited 75-95% of the O(3) removal capacity of unloaded
      samples. O(3) breakthrough and removal capacity were not strongly influenced by
      the VOC-loading rate. Toluene-loaded filters showed rapid O(3) breakthrough due
      to poisoning of the AC, while pseudo-poisoning (initially higher O(3) adsorption
      rates that rapidly decrease) is suggested for limonene-loaded filters. Overall,
      VOC loadings provide an overall reduction in chemisorption rates, a modest
      reduction in O(3) removal capacity, and sometimes dramatic changes in
      breakthrough behavior, important considerations in filter applications in
      environments where both O(3) and VOCs are present.

PMID- 15961140
TI  - Synchronous-scan fluorescence spectra of Chlorella vulgaris solution.
AB  - The characterization of the Chlorella vulgaris solution was carried out using
      synchronous-scan spectroscopy. The range of concentration of algae and Fe(III) in
      aqueous solutions were 5 x 10(8)-8 x 10(9) cells l(-1) and 10-60 microM,
      respectively. Effective characterization method used was synchronous-scan
      fluorescence spectroscopy. The wavelength difference (Deltalambda) of 90 nm was
      maintained between excitation and emission wavelengths; 90 nm was found to be the
      best Deltalambda for effective characterization of Chlorella vulgaris solution
      with or without quencher species (e.g., Fe(III), humic acid (HA)) for the first
      time. The peak was observed at about EX 236.6 nm/EM 326.6 nm for synchronous-scan
      fluorescence spectra. The fluorescence quenching of algae in system of algae
      Fe(III)-HA was studied using synchronous-scan spectroscopy for the first time.
      Fe(III) was clearly the effective quencher. The relationship between I0/I
      (quenching efficiency) and c (concentration of Fe(III) added) was a linear
      correlation for the algae solution with Fe(III). Also, Aldrich humic acid was
      found to be an effective quencher. pH effect on synchronous-scan fluorescence
      intensity of algal solution with Fe(III) and/or HA was evident.

PMID- 15961141
TI  - Clinical implications for patients on antithrombotic therapy while taking
      supplements.

PMID- 15961142
TI  - Resolution of nocturnal enuresis in snoring children after treatment with nasal
      budesonide.
AB  - Nocturnal enuresis has been associated with obstructive sleep apnea-hypopnea and
      may resolve after adenotonsillectomy. Nasal corticosteroids have improved
      symptoms and polysomnography findings in children with snoring. Two children with
      primary nocturnal enuresis, chronic nasal obstruction, and loud snoring underwent
      polysomnography. The apnea-hypopnea index was 4.9 and 7.3 episodes/hr, and the
      oxygen desaturation of hemoglobin index was 4.6 and 5.2 episodes/hr. After
      administration of budesonide, the frequency of snoring decreased, the
      polysomnography findings improved, and the enuresis resolved completely. Six
      months after treatment, both children were still dry at night. Administration of
      nasal corticosteroids is associated with resolution of enuresis in children with
      mild obstructive sleep-disordered breathing.

PMID- 15961143
TI  - Periprostatic pheochromocytoma.
AB  - In adults, 10% of pheochromocytomas are extra-adrenal. Most extra-adrenal
      pheochromocytomas occur in the organ of Zuckerkandl. Occasionally,
      pheochromocytomas can arise from paraganglion chromaffin cells in other
      locations. We present the case of a 63-year-old hypertensive man with a
      periprostatic pheochromocytoma. Our patient underwent surgical extirpation of the
      pheochromocytoma, while sparing the prostate from resection. His blood pressure
      has remained well controlled postoperatively without the addition of
      antihypertensive medications.

PMID- 15961144
TI  - Partial adrenalectomy: the National Cancer Institute experience.
AB  - OBJECTIVES: To report our experience of partial adrenalectomy and demonstrate
      whether adrenal function can be preserved in patients with hereditary adrenal
      pheochromocytoma. Total adrenalectomy has largely been used in the treatment of
      patients with hereditary adrenal pheochromocytomas. Adrenal cortical-sparing
      surgery is an alternative approach that aims to balance tumor removal with
      preservation of adrenocortical function. METHODS: From 1995 to 2004, 33 patients
      with hereditary pheochromocytoma presented with adrenal masses. Partial
      adrenalectomy (open or laparoscopic) was performed if normal adrenocortical
      tissue was evident on preoperative imaging or intraoperative ultrasonography.
      Various operative parameters, as well as postoperative function of the residual
      adrenal remnants, were determined. RESULTS: Of the 33 patients, 8 underwent open
      partial adrenalectomy and 25 laparoscopic partial adrenalectomy during a 10-year
      period. Ten patients underwent simultaneous, bilateral partial adrenalectomy and
      8 underwent surgery on a solitary adrenal gland, 4 of whom received postoperative
      steroid replacement (stopped in 3 after 1 to 3 months). All other patients had
      normal catecholamine levels and remained tumor free by imaging at a mean follow
      up of 36 months (range 3 to 102). CONCLUSIONS: Partial adrenalectomy can preserve
      adrenal function in patients with adrenal masses. The laparoscopic approach is
      technically safe and associated with less morbidity without compromising tumor
      removal. With careful surgical planning, especially in patients with tumors in
      solitary glands, adrenocortical function may be preserved, thereby avoiding the
      morbidity associated with medical adrenal replacement.

PMID- 15961145
TI  - Study of lymphatic mapping and sentinel node identification in early stage
      cervical cancer.
AB  - OBJECTIVE: The aim of our study was to compare the identification of sentinel
      lymph nodes (SLN) by blue dye and (99m) Tc; to evaluate detection rate per
      patient and specific side detection rate (SSDR) of SLN, distribution of SLN and
      distribution of positive SLN and false negative rate of the methods. PATIENTS AND
      METHODS: From February 2000 until September 2004, we included 183 women with
      early stage cervical carcinoma. We evaluated two methods of detection of SLN (100
      cases by Patent blue, 83 cases by Patent blue with (99m)Tc). We stratified the
      group upon the size of the tumor and upon the type of surgical method
      (laparoscopy, laparotomy). RESULTS: SLN identification increased in cases when we
      used combination of both methods (Tc + blue dye) SSDR = 93% versus the use of
      blue dye only SSDR = 71% (OR:5,76, CI 95% -2.9 -11.4, <0.0001). Distribution of
      462 SLN-45.0% external iliac artery and vein, 42.6% supraobturator, 4.8
      bifurcation and common illiac artery and vein, 4.6% praesacral, 3% medial part of
      lateral parametrium. Distribution of 44 positive SLN-approximately 38.6% external
      illiac artery and vein, 45.5% supraobturator, 6.8% bifurcation and common illiac
      artery and vein, 4.5% praesacral, 4.5% medial part of lateral parametrium. One
      false negative SN was in presacral area. CONCLUSION: Detection of SLN by
      combination of (99m)Tc and blue dye was statistically significantly better than
      blue dye alone. Our study documents high sensitivity, specificity and low false
      negativity of the method.

PMID- 15961147
TI  - Endogenous opioids are necessary for benzodiazepine palatability enhancement:
      naltrexone blocks diazepam-induced increase of sucrose-'liking'.
AB  - Opioid agonists and benzodiazepine agonists each increase food intake. Both also
      increase hedonic 'liking' reactions to sweet tastes in rats. Do opioids and
      benzodiazepines share overlapping mechanisms of hedonic impact? Or are
      benzodiazepine and opioid effects on hedonic impact mediated by independent
      mechanisms? The present study examined whether blockade of opioid receptors
      prevents benzodiazepine-induced enhancement of taste palatability, as assessed by
      the affective taste reactivity test. Rats were implanted with oral cannulae, and
      prior to an oral infusion of bittersweet quinine-sucrose solution, all received
      i.p. injections of either vehicle, or diazepam alone (5 mg/kg diazepam+0 mg/kg
      naltrexone), naltrexone alone (1 mg/kg naltrexone+0 mg diazepam), or both
      diazepam plus naltrexone (5 mg/kg diazepam+1mg/kg naltrexone). Videotaped hedonic
      ('liking') and aversive ('disliking') orofacial reactions elicited by
      sucrose/quinine taste were compared across drug conditions. Diazepam
      administration alone more than doubled hedonic 'liking' reactions to the
      bittersweet taste, while reducing 'disliking' in half, compared to vehicle
      levels. Naltrexone by itself had little effect on taste-elicited affective
      reactions, and only marginally increased aversive gapes. However, naltrexone
      completely blocked diazepam's enhancement of positive hedonic 'liking' reactions,
      and naltrexone similarly disrupted diazepam-reduction of aversive 'disliking'
      taste reactions. These results indicate that endogenous opioid neurotransmission
      may be crucial to benzodiazepine enhancement of hedonic 'liking' for natural
      taste reward.

PMID- 15961146
TI  - Anxiolytic-like effect of milnacipran in the four-plate test in mice: mechanism
      of action.
AB  - Milnacipran is a serotonin/noradrenaline reuptake inhibitor (SNRI) which has not
      yet been systematically studied preclinically or clinically for the treatment of
      anxiety disorders. In the four-plate test (FPT) which is known to predict
      anxiolytic-like activity in mice, milnacipran (4, 8, 16 and 32 mg/kg)
      demonstrated strong anti-punishment effects following acute administration. The
      anxiolytic-like effect of milnacipran was not reversed by the selective GABA(A)
      receptor antagonist, flumazenil (2 and 4 mg/kg), the selective alpha1
      adrenoceptor antagonist, prazosin (0.5 and 2 mg/kg), the selective alpha2
      adrenoceptor antagonist, idazoxan (1 and 4 mg/kg) or the selective 5-HT2B
      receptor antagonist, SB 206553 (0.1 and 1 mg/kg). In contrast, the selective 5
      HT2A receptor antagonist, SR 46349B (0.1 and 1 mg/kg), and the non-selective 5
      HT2 receptor antagonist, ketanserin (0.125 and 0.5 mg/kg), completely abolished
      the anxiolytic-like effect of milnacipran in FPT. Neurochemical depletion of NA
      or 5-HT completely abolished the activity of milnacipran. These results strongly
      suggest that activation of 5-HT2A receptors is critically involved in the
      anxiolytic activity of milnacipran. On the other hand the lack of activity of
      milnacipran after depletion of NA or 5-HT is consistent with milnacipran acting
      on the locus coeruleus to induce 5-HT release. The present data suggest a strong
      connection between 5-HT2A receptors and NA neurotransmission.

PMID- 15961148
TI  - Fertility of yearling beef bulls during mating.
AB  - Crossbred (Bos taurus) yearling beef bulls were assessed for breeding soundness
      and physical traits prior to multi-sire natural mating at pasture. Bulls (n = 60)
      were assigned to six groups of nine or 10 bulls and two bull-groups were rotated
      on 14-day intervals during a 63-day mating season in each breeding herd (n = 3)
      of 191-196 cows. The remaining bulls (n = 14) were maintained under similar
      environmental conditions without mating exposure. Bulls were observed during
      mating and assessed for breeding soundness and changes following mating. Bulls
      used for breeding (UFB) lost 77 kg of body weight and declined from body
      condition scores of 6 to 4.5, whereas bulls not used for breeding (NUB)
      maintained body condition scores of 6 and gained 27 kg. The UFB bulls incurred a
      75% total injury rate with 63% incidence of lameness and 12% incidence of
      reproductive injuries, resulting in a 22% attrition rate. Only 45% were
      physically sound at the end of mating. Scrotal circumference declined in UFB
      bulls (-4.58%) and increased in NUB bulls (2.49%). From the 98% BSE-satisfactory
      rate (UFB) prior to breeding, only 61% were BSE-satisfactory post-breeding. The
      NUB bulls declined from 57 to 36% satisfactory. The BSE classification was
      influenced by significant increases in abnormal spermatozoa (primary and
      secondary), which was significantly associated with injuries incurred during
      mating. Group and breed differences in injury rates and BSE-status following
      mating were evident. Environmental conditions and mating activity influenced bull
      seminal quality and physical condition. Pregnancy rates in all three breeding
      herds (91-96%) were similar, with insignificant differences between bull-groups;
      the effects of physical and reproductive changes on individual bull fertility
      were immeasurable.

PMID- 15961149
TI  - Prevalence of endometritis and its effects on reproductive performance of dairy
      cows.
AB  - Hostein cows (n=141) in five commercial dairy herds in central New York were
      examined for endometritis by examination of endometrial aspirates for presence of
      inflammatory cells, principally neutrophils, by endometrial cytology at 40-60
      days postpartum. The prevalence of cytologically-diagnosed endometritis was 53%;
      within herds the prevalence varied from 37 to 74% (P=0.02). There was excellent
      agreement between two examiners (Kappa=0.864; P<0.0001). Parity did not influence
      prevalence of endometritis (P=0.53). Cytologically diagnosed endometritis was
      associated with profoundly impaired reproductive performance; Kaplan-Meier
      survival analysis revealed lower overall pregnancy rate (P<0.0001). Median days
      open was 206 for cows with endometritis and 118 for cows free of the condition.
      Overall, 76% of cows in this study became pregnant by 300 days postpartum; 63% of
      cows with endometritis and 89% of cows without endometritis were confirmed
      pregnant by 300 days postpartum (P<0.003). (For these two groups, 69, and 90%
      respectively, became pregnant during the duration of the study). Pregnancy to
      first service percentage was lower (11 versus 36%; P=0.001) for cows with than
      without endometritis, and these cows required more services before 50% became
      pregnant (3 versus 2; P=0.006). In a second study using 22 cows in a university
      owned herd, the prevalence of cytological evidence of inflammation was 100% at 2
      weeks postpartum, and dropped to 89, 58, and 41% at 4, 6, and 8 weeks,
      respectively. Endometritis diagnosed by endometrial cytology late in the
      voluntary waiting period was highly prevalent and exerted a profoundly
      detrimental effect on subsequent reproductive performance, making this condition
      potentially extremely costly to the North American dairy industry.

PMID- 15961150
TI  - Diagnostic applications of ultrasonography to stallion's reproductive tract.
AB  - Although ultrasound evaluation of the reproductive tract of stallions was
      introduced to veterinary practice long ago, this examination is not always
      conducted during routine breeding soundness evaluation. The objective of this
      study was to investigate the clinical relevance of routine ultrasound evaluation
      of the stallion's reproductive tract. Breeding soundness evaluation of 113
      stallions was performed, including ultrasonography of external and internal
      genitalia. Various pathological conditions were detected using this technique,
      with the most frequent being varicocele, thickened vaginal tunics and cystic
      structures. Varicocele and thickened vaginal tunics were associated with
      decreased quality of semen, while cysts of the epididymal head, urethra and
      uterus masculinus were frequently associated with ejaculatory problems. These
      findings suggested that routine ultrasound evaluation of breeding stallions may
      be very helpful in detecting pathological conditions that may impact their
      reproductive career.

PMID- 15961151
TI  - Influence of extender, freezing rate, and thawing rate on post-thaw motility,
      viability and morphology of coyote (Canis latrans) spermatozoa.
AB  - The objective of this study was to examine the post-thaw effects of three
      cryoprotective extenders (Tris-fructose-citric acid extender, Tris-glucose-citric
      acid extender, and lactose extender), three linear freezing rates (-1, -6, and 
      20 degrees C/min), and three thawing rates (37 degrees C water bath for 120s, 60
      degrees C water bath for 30s, and 70 degrees C water bath for 8s) on coyote
      spermatozoa. After thawing, the findings supported that cryopreservation of
      coyote (Canis latrans) spermatozoa frozen at a moderate freezing rate (-6 degrees
      C/min), in either a Tris-fructose or Tris-glucose extender, and thawed at a slow
      rate (37 degrees C water bath for 120s) or moderate rate (60 degrees C water bath
      for 30s), resulted in a more vigorous post-thaw motility (range, 57.5-44.0%) and
      viability (range, 64-49.6%) with the least amount of morphological and acrosomal
      abnormalities.

PMID- 15961152
TI  - Evidence-based practice in stuttering: Some questions to consider.
AB  - A recent forum in JFD (28/3, 2003) evaluated the status of evidence-based
      practice in fluency disorders, and offered recommendations for improvement. This
      article re-evaluates the level of support available for some popular approaches
      to stuttering therapy and questions the relative value placed on some types of
      programs endorsed by the forum. Evidence-based practice is discussed within the
      context of emerging concerns over its application to non-medical interventions
      and suggestions are made for grounding fluency interventions by reference to
      empirically supported principles of change. A popular, evidence-based
      intervention for stuttering in young children (the Lidcombe program) is evaluated
      within the suggested parameters. EDUCATIONAL OBJECTIVES: After reading this
      article, the reader will be able to: (1) evaluate the status of evidence-based
      practice in fluency disorders; (2) list concerns about the impact of narrow
      interpretation of EBP on research and practice in the field of fluency disorders
      and other non-medical domains; (3) articulate the role of theory and basic
      research in selecting among and evaluating therapy approach options.

PMID- 15961154
TI  - The Court for Sexual Offences: perceptions of the families of the victims of
      sexual offences.
AB  - This article aims to evaluate the degree to which the Court for Sexual Offences
      in Bloemfontein, Free State, South Africa and associated auxiliary institutions
      meet the needs of the families of the victims of sex-crimes. The perceptions of
      24 family members of victims were obtained. These individuals generally perceived
      the functioning of the Court and its auxiliary institutions in a positive light.
      However, perceptions of the time that cases took to come to trial and the
      standard of post-trial interaction between the Court and the families was not
      positive. A need for more effective victim-care at both social and psychological
      levels was identified. Future psycho-legal research possibilities in this largely
      neglected field are highlighted.

PMID- 15961153
TI  - The crystallization of an aluminosilicate glass in the K2O-Al2O3-SiO2 system.
AB  - OBJECTIVES: The aims of the study were to explore the nucleation and
      crystallization kinetics of an aluminosilicate glass in K2O-Al2O3-SiO2 system and
      to characterize it. OBJECTIVES: A starting glass composition of wt%; 64.2% SiO2,
      16.1% Al2O3, 10.9% K2O, 4.3% Na2O, 1.7% CaO, 0.5% LiO and 0.4% TiO2 was heated in
      an electric furnace and later quenched to produce glasses. The glass powders were
      heat treated using differing heat treatment schedules and quenched. Dta, Xrd, Eds
      and Sem analyses were used to characterize and explore the crystallization
      kinetics of the glasses. RESULTS: Phase separation of the glasses was identified
      and characterized in the glasses. Tetragonal leucite, cubic leucite and sanadine
      glass-ceramics were produced. Fine leucite crystals (1 microm2) were crystallized
      with minimal matrix microcracking. SIGNIFICANCE: Amorphous phase separation
      appeared to be an important precursor to nucleation and crystal growth in the
      alkali aluminosilicate glasses explored. It was possible to control the
      crystallization of tetragonal leucite and sanidine phases by selected heat
      treatment of glass powders and monoliths, resulting in the production of fine
      grained tetragonal leucite glass-ceramics.

PMID- 15961155
TI  - The Court for Sexual Offences: perceptions of the victims of sexual offences.
AB  - This article explores the perceptions of sexual offence victims following their
      interaction with the Court for Sexual Offences in Bloemfontein, Free State, South
      Africa. The study primarily investigates these individuals' satisfaction with the
      degree to which the Court succeeds in providing more effective justice for
      victims and reduces secondary victimization during judicial proceedings. The
      respondents were generally positive with regard to their experiences with the
      Court. However, cases were still found to be slow in coming to trial. The
      treatment of the victims after their participation in the trials was found not to
      be of the same standard as that received before they testified. These findings
      point to potential changes to the current system to further enhance the Court's
      functioning and legitimacy amongst the people who make use of its services.

PMID- 15961156
TI  - On intelligence and crime: a comparison of incarcerated sex offenders and serious
      non-sexual violent criminals.
AB  - The impact of low IQ on crime has been a focus of debate for several decades now.
      Although sociologists have virtually removed it from the list of possible factors
      influencing crime, the impact of IQ on crime continues to generate a significant
      amount of scientific research and a substantial number of publications. The
      purpose of this study is to assess intellectual levels and to compare two groups
      of incarcerated criminals. Using MANCOVA and ANCOVA procedures, 261 sex offenders
      and 150 non-sexual violent criminals were compared on IQ subscales. The results
      show significant differences on vocabulary, comprehension, arithmetic, mental
      math computations, object assembly, letter-number sequencing, and perception
      subscales, as well as on performance IQ and total IQ. The impacts of penal
      filtering and sample composition are hypothesized to explain differences between
      the two subgroups. Theoretical and practical implications are discussed.

PMID- 15961157
TI  - Selective and efficient inhibition of the alternative pathway of complement by a
      mAb that recognizes C3b/iC3b.
AB  - The alternative pathway (AP) of the complement system plays an important role in
      tissue damage and inflammation associated with certain autoimmune diseases and
      with ischemia-reperfusion injury. Selective inhibition of the AP could prevent
      such pathologies while allowing the classical and lectin pathways of complement
      activation to continue to provide protection. Here we present data describing
      selective inhibition of the AP of complement by anti-C3b/iC3b monoclonal antibody
      (mAb) 3E7, and by a chimeric, "deimmunized" form of this mAb, H17, which contains
      the human IgG1 Fc region and was further modified by substitution of amino acids
      in order to remove T cell epitopes. Both mAbs block AP-mediated deposition of C3b
      onto zymosan or Sepharose 4B, and they also inhibit AP-promoted lysis of rabbit
      erythrocytes. MAbs 3E7 and H17 also successfully compete with both factors B and
      H for binding to C3b-opsonized substrates, and the ability of both mAbs to
      inhibit the AP is blocked by pre-incubation with two different sources of
      C3(H2O). Kinetic measurements demonstrate that mAb 3E7 effectively stops
      progression of C3b deposition after AP activation is initiated. Our results
      therefore suggest that these mAbs block activation of the AP by binding to both
      C3(H2O) and to C3b, and thus prevent binding and activation of factor B. Based on
      these and other observations, mAb H17 may find future use in therapeutic
      applications focused on selective inhibition of the AP.

PMID- 15961158
TI  - Complement: a nostalgic journey The Hans J. Muller-Eberhard Memorial Lecture,
      Honolulu, June 14, 2004.
AB  - The scientific career and research contributions of Hans J. Muller-Eberhard to
      the field of complement research are presented in historical context, and
      interpreted with regard to the state of the field and the research technologies
      available when the contributions were made.

PMID- 15961159
TI  - Anatomic and visual outcomes of scleral buckling versus primary vitrectomy in
      pseudophakic and aphakic retinal detachment: six-month follow-up results of a
      single operation--report no. 1.
AB  - PURPOSE: To compare the anatomic and visual results and complications of
      conventional scleral buckling versus primary vitrectomy for management of
      pseudophakic and aphakic retinal detachment. DESIGN: Prospective, randomized,
      multicenter clinical trial. PARTICIPANTS: Two hundred twenty-five eyes of 225
      patients with pseudophakic or aphakic retinal detachment. INTERVENTION: Eligible
      eyes were assigned randomly either to conventional scleral buckling or primary
      vitrectomy without any buckle. MAIN OUTCOME MEASURES: Visual results, retinal
      reattachment rate, proliferative vitreoretinopathy, macular pucker, cystoid
      macular edema, choroidal detachment, intraocular pressure, extraocular muscle
      dysfunction, and anisometropia. RESULTS: There were no statistically significant
      differences between the 2 treatment groups regarding the single-operation retinal
      reattachment rate at the 1-, 2-, 4-, and 6-month follow-up examinations. Patients
      in the buckle group had 28% greater likelihood of anatomic success compared with
      those in the vitrectomy group (odds ratio, 1.28; 95% confidence interval, 0.73
      2.24), indicating no statistically significant difference. Proliferative
      vitreoretinopathy was the main cause of anatomic failure in both groups and
      occurred independent of the surgical technique used. Best-corrected visual acuity
      at the 1-, 2-, 4-, and 6-month postoperative follow-up examinations showed no
      statistically significant difference between the 2 groups. Six months after
      surgery, 12.8% of eyes in the buckle group and 11.3% of eyes in the vitrectomy
      group achieved visual acuity of 20/40 or better. The difference between the 2
      groups was not statistically significant. Corresponding figures were 66.3% and
      64.5% for visual acuity of 20/200 or better in the buckle and vitrectomy groups,
      respectively, again with no statistically significant difference. There were no
      statistically significant differences in rates of complications. CONCLUSIONS:
      Scleral buckling and primary vitrectomy without an encircling band have
      comparable results in pseudophakic and aphakic retinal detachment. The choice of
      surgical technique depends on various factors, including patient compliance, cost
      of surgery, experience and capability of surgeons, and availability of
      appropriate instrumentation.

PMID- 15961160
TI  - Nanomolar aluminum induces pro-inflammatory and pro-apoptotic gene expression in
      human brain cells in primary culture.
AB  - Aluminum, the most abundant neurotoxic metal in our biosphere, has been
      implicated in the etiology of several neurodegenerative disorders including
      Alzheimer's disease (AD). To further understand aluminum's influence on gene
      expression, we examined total messenger RNA levels in untransformed human neural
      cells exposed to 100 nanomolar aluminum sulfate using high density DNA
      microarrays that interrogate the expression of every human gene. Preliminary data
      indicate that of the most altered gene expression levels, 17/24 (70.8%) of
      aluminum-affected genes, and 7/8 (87.5%) of aluminum-induced genes exhibit
      expression patterns similar to those observed in AD. The seven genes found to be
      significantly up-regulated by aluminum encode pro-inflammatory or pro-apoptotic
      signaling elements, including NF-kappaB subunits, interleukin-1beta precursor,
      cytosolic phospholipase A2, cyclooxygenase-2, beta-amyloid precursor protein and
      DAXX, a regulatory protein known to induce apoptosis and repress transcription.
      The promoters of genes up-regulated by aluminum are enriched in binding sites for
      the stress-inducible transcription factors HIF-1 and NF-kappaB, suggesting a role
      for aluminum, HIF-1 and NF-kappaB in driving atypical, pro-inflammatory and pro
      apoptotic gene expression. The effect of aluminum on specific stress-related gene
      expression patterns in human brain cells clearly warrant further investigation.

PMID- 15961161
TI  - Structural and dynamic properties of Synechocystis sp. PCC 6803 Hb revealed by
      reconstitution with Zn-protoporphyrin IX.
AB  - In its resting state, the truncated globin of the cyanobacterium Synechocystis
      sp. PCC 6803 exhibits hexacoordination of the heme iron, with His46 (E10) and
      His70 (F8, proximal) serving as axial ligands. Diatomic ligands displace the
      distal His46 (E10) from the ferric and ferrous iron and promote considerable
      structural changes in the B helix, E helix, and EF regions. Here, Zn(II)
      substituted hemoglobin was used to explore the role of distal ligands in
      stabilizing the heme pocket structure. NMR data showed that the Zn ion was
      coordinated by the four pyrrole nitrogens and by His70 (F8) only. The proximal
      side of the Zn-porphyrin adopted a geometry recognizable as that of the wild-type
      protein. Decoordination of His46 (E10) to form the pentacoordinate Zn resulted in
      an incomplete transition to the conformation observed in the ferric, cyanide
      bound protein. The NMR data also demonstrated that the H helix underwent complex
      dynamic processes near His117, a residue readily reacting with the wild-type heme
      2-vinyl group in a post-translational modification.

PMID- 15961162
TI  - Raised intracranial pressure complicating cryptococcal meningitis: immune
      reconstitution inflammatory syndrome or recurrent cryptococcal disease?
AB  - We report the case of a patient with advanced HIV disease and cryptococcal
      meningitis, who after an initially good clinical and mycological response to
      systemic anti-fungal treatment developed symptomatic raised intracranial pressure
      10 days after initiation of highly active anti-retroviral therapy. We describe
      the subsequent clinical management and the features that suggest that this
      persistently raised ICP was more likely due to an immune reconstitution syndrome
      (IRIS) following HAART rather than relapse of cryptococcal disease or failure of
      anti-fungal therapy.

PMID- 15961163
TI  - Genetic variability of principal neutralizing determinants on HIV-1 gp41 and its
      correlation with subtypes.
AB  - Several neutralizing determinants have been identified on HIV-1 envelope
      glycoprotein gp41: LGIWGCSGKLIC (HXB2: aa593-604), ELDKWA (aa662-667), NWFDIT
      (aa671-676), and ERDRDR (aa739-744). Restricted mutations were observed on these
      epitopes. In this study, the genetic variability of these neutralizing
      determinants in 3799 isolates from different M-group subtypes (A, B, C, D, F, G,
      H, CRF01_AE and CRF02_AG) and O group was analyzed. Many variants were found to
      be closely correlated with certain subtypes. These subtype-related variants could
      be recruited into the subtype identification and subtype-specific vaccine
      development.

PMID- 15961164
TI  - Oxidants and antioxidants in tonsillar and adenoidal tissue in chronic
      adenotonsillitis and adenotonsillar hypertrophy in children.
AB  - OBJECTIVE: The aim of the study is to determine the possible role of oxidants and
      antioxidants in the pathogenesis of chronic adenotonsillitis and adenotonsillar
      hypertrophy in children. PATIENTS AND METHODS: The children were divided into
      infection and hypertrophy groups, which were comparable according to age and
      gender distribution. The infection group was consisted of 20 children with the
      diagnosis of chronic adenotonsillitis and the hypertrophy group was made up of 19
      children with adenotonsillar hypertrophy to whom adenotonsillectomy was
      performed. Preoperative blood levels of erythrocyte MDA, serum MDA, erythrocyte
      catalase and serum catalase, and adenoidal and tonsillar tissue levels of MDA and
      catalase were studied. RESULTS: There were significant increase in tonsil MDA,
      adenoid MDA, tonsil catalase and adenoid catalase levels in infection group
      (p<0.05). CONCLUSION: Oxidants and antioxidants are found to have an important
      role in the pathogenesis of adenotonsillar hypertrophy and chronic
      adenotonsillitis. These findings strengthen the hypothesis that indicates
      adenotonsillar hypertrophy and chronic adenotonsillitis are different diseases of
      the same tissues.

PMID- 15961165
TI  - Tonsillectomy using the Ligasure vessel sealing system. A preliminary report.
AB  - OBJECTIVE: To evaluate and introduce a new method of tonsillectomy with the use
      of Ligasure vessel sealing system (LVSS) in pediatric population. METHOD: A
      prospective study was conducted on children undergoing tonsillectomy with the use
      of LVSS. Indications included chronic tonsillitis, peritonsilar abscess history,
      and obstructive sleep apnea syndrome. Patients undergoing adenoidectomy, or any
      procedure together with tonsillectomy, and patients with bleeding disorders were
      excluded. Among the available head-pieces, the 'Precise' instrument was used,
      both as haemostatic and dissection tool. Intraoperative bleeding, operative time,
      and complication rates, were evaluated. RESULTS: Our series consisted of 83
      children among 103 patients undergone LVSS tonsillectomy. There was no measurable
      bleeding during surgery in any of the cases. In 18 children limited peritonsilar
      edema was noticed. No postoperative hemorrhage or other complication occurred.
      Mean operative time was 16 min. CONCLUSIONS: LVSS was found quite effective and
      safe, providing sufficient haemostasis, minimal intraoperative blood loss, and
      safety against the variant Creutzfeld-Jakob disease transmission.

PMID- 15961166
TI  - Pediatric postcricoid vascular malformation: a diagnostic and treatment
      challenge.
AB  - Hemangioma of the upper aerodigestive tract is a rarely reported occurrence in
      the pediatric literature. To date, there have been three published case reports
      of postcricoid hemangiomas contributing to unexplained dysphagia and respiratory
      distress. We present three children with a history of swallowing difficulty and
      stridor who were found to have an occult postcricoid mass. Valsalva maneuvers
      confirmed the suspicion of a vascular malformation in both patients. Transoral
      laser therapy (KTP and CO2) was used to ablate the lesions. The patients are
      symptom-free at 5 months, 5 years, and 2 weeks, respectively. The diagnostic
      challenge in evaluating these children and the therapeutic choices are described.

PMID- 15961167
TI  - Two RT-PCR based assays to detect human metapneumovirus in nasopharyngeal
      aspirates.
AB  - Two sensitive and specific RT-PCR assays were standardised for testing the
      presence of human metapneumovirus. A total of 300 nasopharyngeal aspirates
      collected from infants suffering from bronchiolitis since October 2000 to June
      2003 and shown previously as negative to common respiratory viruses were
      examined. Matrix and polymerase viral genes, which show a low rate of variation,
      were chosen to design amplification assays to ensure that any genotype of the
      human metapneumovirus could be detected. A RT-PCR followed by a reverse line
      blotting hybridisation was developed for viral polymerase gene. For the matrix
      gene, after the RT-PCR assay, a subsequent nested PCR was carried out. Both
      assays had similar sensitivity, equivalent to 0.1 TCID50 of human metapneumovirus
      strain NL/1/99 which was used as the positive control. The human metapneumovirus
      was present in 16.6% of the specimens studied. The approaches described below are
      not only a robust method for rapid diagnosis of the human metapneumovirus, but
      also to establish an etiological surveillance tool for epidemiological studies.
      Based on the results obtained, human metapneumovirus infections in Madrid
      followed a seasonal pattern, with most of the infections occurring between
      February and April.

PMID- 15961168
TI  - Development and evaluation of Varicella zoster virus ELISA for oral fluid
      suitable for epidemiological studies.
AB  - An enzyme-linked immunosorbent assay (ELISA) for detection of Varicella zoster
      virus (VZV) antibodies in oral fluid is described. The assay was optimised and
      evaluated using paired serum and oral fluid from healthy adult volunteers (n =
      205) and preschool children (n = 98), oral fluid samples collected for routine
      measles, mumps and rubella testing (n = 537) and samples from a study of atopic
      dermatitis (n = 252). As chickenpox is predominantly a childhood disease and most
      adults are immune, it was crucial to have samples from children aged 1-5 years to
      evaluate the assay. Mixture modelling of the oral fluid results was used to
      determine the optimum cut-off, sensitivity and specificity of the assay. Compared
      to paired sera tested by the same ELISA the sensitivity of the oral fluid assay
      was 93% and specificity 95.7% overall, varying slightly with age group. The assay
      was shown to have good potential for use in large-scale epidemiological studies.

PMID- 15961169
TI  - Development of a homogeneous screening assay for automated detection of antiviral
      agents active against severe acute respiratory syndrome-associated coronavirus.
AB  - The severity and global spread of the 2003 outbreak of the severe acute
      respiratory syndrome-associated coronavirus (SARS-CoV) highlighted the risks to
      human health posed by emerging viral diseases and emphasized the need for
      specific therapeutic agents instead of relying on existing broadly active
      antiviral compounds. The development of rapid screening assays is essential for
      antiviral drug discovery. Thus, a screening system for anti-SARS-CoV agents was
      developed, which evaluated compound potency, specificity and cytotoxicity at the
      initial screening phase. Cell lines were engineered to constitutively express an
      enhanced green fluorescent protein (EGFP) and used to detect (1) antiviral
      potency in SARS-CoV infection tests; (2) antiviral specificity in tests using the
      porcine coronavirus transmissible gastroenteritis virus (TGEV); and (3)
      cytotoxicity in the same assays without virus challenge. The assay system
      involves minimal manipulation after assay set-up, facilitates automated read-out
      and minimizes risks associated with hazardous viruses. The suitability of this
      assay system in drug discovery was demonstrated by screening of 3388 small
      molecule compounds. The results show that these assays can be applied to high
      throughput screening for identification of inhibitors selectively active against
      SARS-CoV.

PMID- 15961170
TI  - Quantitative detection of HIV-1 RNA using NucliSens EasyQ HIV-1 assay.
AB  - HIV-1 RNA viral load has become the major biological marker for disease prognosis
      and outcome of antiretroviral therapy in the treatment of HIV-infected
      individuals. The aim of this study was to compare the performance of the new CE
      marked NucliSens EasyQ HIV-1 assay with NucliSens HIV-1 QT assay (reference
      method). NucliSens EasyQ HIV-1 (EasyQ) couples nucleic acid sequence-based
      amplification (NASBA) with real-time detection using molecular beacons utilizing
      the NucliSens EasyQ analyzer. NASBA is a sensitive, isothermal, transcription
      based amplification system designed specifically for the detection of RNA
      targets. There was significant correlation (r = 0.878, P < 0.0001) between the
      two different assays in the analysis of clinical samples and the frequency of
      concordant results (log difference <0.5) was 74%. The two assays detected HIV-1
      RNA in 81 specimens, and neither detected (below the lower detection limit, 400
      copies/ml for NucliSens HIV-1 QT and 500IU/ml for EasyQ) HIV-1 RNA in 12
      specimens. Three clinical specimens had detectable HIV-1 RNA using the EasyQ
      only, and two specimens had detectable HIV-1 RNA using the NucliSens HIV-1 QT
      only. The EasyQ procedure can analyze 48 clinical samples within 6h. The
      coefficient of variation of EasyQ ranged from 3.0 to 9.5% (3% at 4.9 log; 5.7% at
      3.7 log; 9.5% at 2.7 log). The new assay is shown to be a rapid, convenient, and
      reliable procedure for HIV-1 RNA viral load monitoring.

PMID- 15961171
TI  - Accumulation, transformation and tissue distribution of domoic acid, the amnesic
      shellfish poisoning toxin, in the common cuttlefish, Sepia officinalis.
AB  - Domoic acid (DA) is a phycotoxin produced by some diatoms, mainly from the Pseudo
      nitzschia genus, and has been detected throughout the marine food web. Although
      DA has been frequently found in cephalopod prey such as crustaceans and fish,
      little is known about DA accumulation in these molluscs. This study presents the
      first data showing relevant concentrations of DA detected in the common
      cuttlefish, Sepia officinalis, which is one of the most studied cephalopod
      species in the world. Domoic acid was consistently found throughout 2003 and 2004
      in the digestive gland of cuttlefish reaching concentrations of 241.7 microg DA
      g(-1). The highest DA values were detected during spring and summer months,
      periods when Pseudo-nitzschia occur in the plankton. In fact, Pseudo-nitzschia
      blooms preceded the highest DA concentrations in cuttlefish. Evaluation of DA
      tissue distribution showed elevated DA concentrations in the digestive gland and
      branchial hearts. Further, DA isomers comprised a relevant percentage of the
      toxin profile, indicating degradation and biotransformation of the toxin in the
      branchial hearts. The common cuttlefish, like other cephalopod species, plays a
      central position in the food web and might be a new DA vector to top predators
      like marine mammals. Human intoxications are not expected since DA was only
      seldom detected in the mantle and even then in very low levels (max 0.7 microg DA
      g(-1)). However, in some countries whole juvenile animals are consumed (i.e.
      without evisceration) and in this case they might represent a risk to human
      health. This study contributes to understanding the occurrence of phycotoxins in
      cephalopods and reveals a new member of the marine food web able to accumulate
      DA.

PMID- 15961172
TI  - Interaction of casein kinase 1 delta (CK1 delta) with the light chain LC2 of
      microtubule associated protein 1A (MAP1A).
AB  - CK1delta, a member of the casein kinase 1 family of serine/threonine specific
      kinases, has been shown to be involved in the regulation of microtubule dynamics.
      We have now identified a 176 aa fragment of the light chain LC2 of MAP1A (termed
      LC2-P16) specifically interacting with CK1delta. Two CK1delta interacting domains
      of LC2 were identified, located between aa 2629 and 2753 close to aa 2683 and
      between aa 2712 and 2805 of LC2. The two regions necessary for the interaction of
      LC2 with CK1delta have been mapped between aa 76-103 and aa 351-375 of CK1delta.
      Furthermore, LC2 has been identified as a new substrate of CK1delta. We therefore
      propose a model in which CK1delta could modulate microtubule dynamics by changing
      the phosphorylation status of the light chain LC2 of MAP1A.

PMID- 15961173
TI  - Lipoprotein(a), apolipoprotein(a) polymorphism and coronary atherosclerosis
      severity in type 2 diabetic patients.
AB  - BACKGROUND: Few and conflicting data are available in the literature on the
      association between Lp(a) levels and the severity of coronary artery disease
      (CAD) in diabetic patients. In addition, no studies took into account the role of
      apo(a) polymorphism. The purpose of the present study was to analyse the
      association of the degree of coronary atherosclerosis with Lp(a) levels and
      apo(a) polymorphism in a large group of type 2 diabetic patients. METHODS: The
      study population consisted of 227 consecutive type 2 diabetic patients undergoing
      a routine coronary angiography to evaluate chest pain or suspected CAD. The
      patients were subdivided into four subgroups according to the number of coronary
      arteries diseased: normal arteries (n=26), mono-vessel disease (n=67), bi-vessel
      disease (n=54) and multi-vessel disease (n=80). RESULTS: Lp(a) levels (normal
      arteries: 14.6+/-19.6 mg/dl; mono-vessel disease: 19.0+/-16.4 mg/dl; bi-vessel
      disease: 19.3+/-15.1 mg/dl; multi-vessel disease: 26.5+/-16.8 mg/dl; p<0.001) and
      the percentages of patients with at least one isoform of low molecular weight
      (normal arteries: 23.1%; mono-vessel disease: 38.8%; bi-vessel disease: 75.9%;
      multi-vessel disease: 81.2%; p<0.001) were significantly correlated with
      increasing number of coronary vessels diseased. Multiple logistic regression
      analysis showed that both Lp(a) levels (OR: 1.31; 95% CI: 1.02-4.11) and apo(a)
      polymorphism (OR: 3.43; 95% CI: 1.67-7.05) were independent predictors of CAD
      severity. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) polymorphism
      may be reliable predictors of CAD severity in type 2 diabetic patients.

PMID- 15961174
TI  - Alpha synchronization and anxiety: implications for inhibition vs. alertness
      hypotheses.
AB  - Although there is much evidence that alpha oscillations are linked with processes
      of perception, attention and semantic memory, their functional significance
      remains uncertain. Synchronization in the alpha frequency range is taken to be a
      marker of cognitive inactivity, active inhibition of sensory information, or a
      means of inhibition of non-task relevant cortical areas. Here we propose an
      alternative interpretation which posits that higher alpha power during reference
      interval signifies higher readiness of alpha system to information processing.
      Predictions derived from the inhibition and alertness hypotheses were tested
      during presentation of acoustic stimuli (tone 1000 Hz) and neutral words to 30
      males (18-25 years) with different levels of trait anxiety. On the whole,
      predictions derived from the inhibition theory were not confirmed and findings
      more corresponded to the alertness hypothesis. High-anxiety subjects showed
      higher alpha power during reference interval simultaneously with higher magnitude
      of event-related desynchronization and higher amplitude of phase-locked alpha
      responses. These findings are discussed in terms of functional significance of
      alpha band synchronization and desynchronization.

PMID- 15961175
TI  - Production of glucuronan oligosaccharides using a new glucuronan lyase activity
      from a Trichoderma sp. strain.
AB  - Sinorhizobium meliloti M5N1CS synthesizes a homopolymer of glucuronic acids beta
      (1,4) linked and variably C2 and/or C3O-acetylated. To obtain beta-Delta-(4,5)
      unsaturated oligoglucuronans, various acetylated forms of this bacterial polymer
      were cleaved by a Trichoderma sp. GL2 glucuronan lyase. Oligomers with
      polymerization degrees up to 8 were then produced, purified by liquid
      chromatography (size exclusion and anions exchange) and characterized using 1H
      NMR and ESI-Q/TOF-MS. Finally, the production (in gram quantity) of pure
      unsaturated oligoglucuronans non-acetylated (di- and trisaccharide) was
      investigated thanks to the complete depolymerization of deacetylated glucuronan.

PMID- 15961176
TI  - High through-put characterization of insect morphocryptic entities by a non
      invasive method using direct-PCR of fecal DNA.
AB  - The development of non-invasive molecular techniques is currently increasing,
      particularly in the fields of behavioural ecology and conservation genetics of
      mammals. Surprisingly, genetic studies of Arthropods and particularly the insects
      have not benefited yet from the contributions that non-invasive methods have
      made. Here, we outline a strategy for identifying phytophagous insect genetic
      entities based on direct-PCR of fecal DNA combined with double strand
      conformation polymorphism (DSCP) typing. This allows the differentiation of
      morphocryptic entities within the species Ceutorhynchus assimilis (Coleoptera:
      Curculionidae), a candidate biocontrol agent of a noxious weed. The results
      obtained clearly demonstrate the potential for this method to provide a valuable
      means for genetic and ecological studies of Arthropods.

PMID- 15961177
TI  - Effects of splitting alternative KlCYC1 3'-UTR regions on processing: metabolic
      consequences and biotechnological applications.
AB  - To analyze the functionality of alternative 3'-UTR processing in the yeast
      Kluyveromyces lactis, recombinant forms of the KlCYC1 gene containing the
      proximal (1-713) or the distal (699-1194) 3'-UTR region (positions related to the
      TAA stop codon) were obtained. The cells expressing the gene with proximal 3'-UTR
      showed the same growth phenotype as the wild type. When the gene expressed only
      the distal region, a single transcript was generated and its expression was
      increased in late-growth phases. Cells expressing the alternative distal 3'-UTR
      region showed differences in their levels of cytochrome c biomass and ethanol
      production with respect to the wild type. The split 3'-UTR regions were also
      functional as separate processing units in Saccharomyces cerevisiae. The
      importance of our results in recombinant gene expression applications will be
      discussed.

PMID- 15961178
TI  - Multi-gene gateway clone design for expression of multiple heterologous genes in
      living cells: conditional gene expression at near physiological levels.
AB  - Using Multisite Gateway five-DNA-fragment constructs vectors that enable
      expression of two tandemly situated cDNAs on a single plasmid were developed.
      Heterologous protein production in cells was achieved by modulating respective
      cDNA expression to pre-determined and different levels. Optimization of cDNA
      expression at near physiological protein levels was achieved using promoters from
      four cell cycle-dependent genes. In comparison with conventionally available
      promoters, EF-1alpha or CMV, the promoters used in this study were able to
      modulate cDNA expression levels over a magnitude of approximately 10 or 100-fold,
      respectively. In transiently transfected cells, two different proteins (CPalpha1
      and CPbeta2), which form a heterodimer, each labeled with a different-colored
      fluorescent protein, were successfully synthesized at pre-determined levels from
      their respective cDNAs. The above vectors were designed to contain an FRT/Flp
      recombination site for integration onto chromosomes and for establishment of
      stable clones in HeLa cells by site-specific recombination. In the stable
      transformant cells produced only about 4% of the protein production levels
      measured in the transiently transformed cells. The biological significance of
      these observations is discussed.

PMID- 15961179
TI  - Regiospecific methylation of naringenin to ponciretin by soybean O
      methyltransferase expressed in Escherichia coli.
AB  - Flavonoids found in plants most likely undergo a variety of modification
      reactions such as hydroxylation, glycosylation, and/or methylation. Among these,
      O-methylation has an effect on the solubility and thus on the antimicrobial
      activity of the flavonoids. We analyzed the conversion of naringenin with a
      methyltransferase, SOMT-2, from Glycine max. SOMT-2 was expressed in Escherichia
      coli as a glutathion S-transferase fusion protein. E. coli harboring SOMT-2 was
      grown with daidzein, geninstein, apigenin, naringenin, and quercetin,
      respectively, and reaction products were analyzed with thin layer chromatography
      and HPLC. SOMT-2 could convert apigenin, daidzein, genistein, and quercetin into
      the corresponding 4'-O-methylated compounds such as acacetin, formononetin,
      biochanine A, and 4'-methylated quercetin whereas naringenin turned out to be the
      best substrate tested. SOMT-2 stoichiometically converted naringenin (4',5,7
      trihyroxyflavanone) into a ponciretin (4'-methoxy-5,7-dihydroxyflavanone), whose
      structure was determined by NMR and LC/mass spectral analyses. Considering the
      reactions, SOMT-2 may have a regiospecific methylation activity, resulting in
      transforming 4'-hydroxyl group of flavonoids B-ring to 4'-methyl group.

PMID- 15961180
TI  - [C-reactive protein, leukocyte count and D-dimer monitoring after orthopedic
      surgery: early diagnosis of infectious or thromboembolic complications. Part one:
      C-reactive protein and leukocyte count as an aid in diagnosing postoperative
      infection].
AB  - OBJECTIVES: To evaluate the usefulness of monitoring C-reactive protein (CRP)
      level and leukocyte count for early diagnosis of infection following orthopedic
      surgery. METHOD: A cohort of 179 patients was followed: group 1 comprised 128
      patients undergoing lower limb arthroplasty, group 2 comprised 29 patients
      undergoing lower limb surgery without implant, and group 3 comprised 22 patients
      undergoing spinal or upper limb surgery. CRP level and leukocyte count were
      systematically measured on admission and then once a week for 4 weeks. Wound
      infections, other infections, wound disconnection without infection and hematoma
      were noted. CRP level and leukocyte count were monitored postoperatively in
      patients with and without complications. RESULTS: CRP level was 4- to 8-fold
      above the normal range at the first postoperative measurement but normalized
      within the next 3 weeks (reaching normal levels by the 30th postoperative day, on
      average). In the 7 cases of wound infection (WI), the CRP level rose to 28-fold
      above normal and was significantly different from that in without infection or
      with intercurrent infection (P<0.01). A receiver operating characteristic (ROC)
      curve was established for CRP level, and for a value of 60 (12-fold above the
      normal range) the sensitivity was 100%, the specificity 83.6% and the negative
      predictive value 100%. The variation in leukocyte count was minor, with a
      significant difference noted between only patients not infected or those with WI
      (P<0.05). DISCUSSION AND CONCLUSIONS: Measurement of CRP level can be used for
      early diagnosis of wound infection. In the case of strong clinical suspicion or
      in the presence of high risk factors, when the level is at 12-fold or more above
      the normal range, the diagnosis of infection is highly probable.

PMID- 15961181
TI  - Factors associated with health care utilization by the elderly in a public health
      care system.
AB  - OBJECTIVE: The objective was to determine the factors associated with the use of
      health care services by the elderly residing in the community. METHODS: A cross
      sectional study on 787 elderly people over 64 years of age from Albacete City
      (Castilla-La Mancha, Spain). The study was carried out by personal home
      interviews during a 9-month period. The dependent variables were: health care
      utilization, and characteristics. The independent variables were: self-reported
      health status, self-reported morbidity, medication use, functional status, mental
      health, lifestyle habits, social support, and sociodemographic status. RESULTS:
      The health care services were used by 74.5% in the last 3 months of which 59.4%
      were general practitioner visits, 18.4% were to nursing staff, and 16.5% were
      specialist visits. Laboratory tests were performed in 39.2% and radiological
      examinations in 24.9%. Emergency visits accounted for 2.4%, and hospitalization,
      2.9%. Users of health care services among the elderly population were objectively
      more ill, although there was a group of healthy individuals who also visited the
      physician and a large group of elderly with considerable health problems who
      never saw their physician. In the multivariate analysis, general practitioner
      utilization was independently associated with a perceived unmet need for care (OR
      = 3.15), a negative self-reported health status (OR = 2.51), and a lower
      educational level (OR = 2.41). CONCLUSIONS: Subjective factors as perceived need
      for care, a negative self-reported health status and lower educational level are
      important factors that influence in the utilization of health care services.

PMID- 15961182
TI  - Induction of heat shock proteins by hyperglycemic cerebral ischemia.
AB  - Hyperglycemia worsens the neuronal death induced by cerebral ischemia. A previous
      study demonstrated that diabetic hyperglycemia suppressed the expression of heat
      shock protein 70 (HSP70) in the liver. The objective of this study is to
      determine whether hyperglycemia exacerbates ischemic brain damage by suppressing
      the expression of heat shock proteins (HSPs) in the brain. Both normoglycemic and
      hyperglycemic rats were subjected to a transient global cerebral ischemia of 15
      min and followed by 0.5, 1 and 3 h of reperfusion. The expression of stress
      related genes and levels of HSP proteins were determined by DNA microarray,
      immunocytochemistry and Western blot analyses. The results showed that
      hyperglycemic ischemia upregulated the expressions of hsp70, hsp90A, hsp90B, heat
      shock cognate 71 kD protein (hsc70) and mthsp70. Protein levels of HSP70 and
      HSP60 were enhanced by hyperglycemia compared with normoglycemia. The results
      suggested that hyperglycemia-exacerbated ischemic brain damage is not mediated by
      the suppression of the HSPs. The increased levels of HSPs and mthsp70 suggest
      that the cell and the mitochondrion had strong stress responses to hyperglycemic
      ischemia.

PMID- 15961183
TI  - Neurotransmission- and cellular stress-related gene expression associated with
      prepulse inhibition in mice.
AB  - Prepulse inhibition (PPI) is a cross-species measure of sensorimotor gating. PPI
      deficits have been associated with a number of neuropsychiatric disorders,
      including schizophrenia. Differential PPI has been demonstrated also across
      various inbred mouse strains; however, the molecular mechanisms underlying these
      differences in sensorimotor gating remain unclear. Here, we sought to identify
      gene expression in the medial prefrontal cortex (mPFC) of mice associated with
      PPI using a laser microdissection and microarray analysis-based approach. C57BL/6
      mouse substrains were used for the study as they have dramatically different PPI.
      Transcriptional analysis of closely related substrains was predicted to reduce
      the detection of genetic variation incidental to the phenotype. Microarray
      analysis comparing the mPFC of C57BL/6J to C57BL/6NHsd mice revealed
      neurotransmission- and cellular stress-related transcriptional responses
      associated with lower PPI. Down-regulation of metabotropic glutamate receptor 5,
      phospholipase C, and inositol monophosphatase 1 gene expression suggest altered
      phosphoinositide signaling, while decreased expression of a gamma-amino-butyric
      acid (GABA)A receptor subunit implies changes in GABAergic signaling. Genes
      involved in neuronal excitation and protection were also differentially
      expressed, including up-regulation of five immediate early genes and anti
      apoptotic/survival factors as Bcl2-associated athanogene 3 and brain-derived
      neurotrophic factor. These data support previous findings of genetic influences
      on PPI, and provide novel insights into the molecular mechanisms regulating
      sensorimotor gating.

PMID- 15961184
TI  - Needlestick injuries in a tertiary care centre in Mumbai, India.
AB  - Accidental exposure from blood/body fluid of patients is a risk to healthcare
      workers (HCWs). Percutaneous injury is the most common method of exposure to
      blood-borne pathogens. A policy was formulated at our institute, a tertiary care
      centre in central Mumbai, and we report a six-year (1998--2003) ongoing
      surveillance of needlestick injuries. Of the 380 HCWs who reported needlestick
      injuries, 45% were nurses, 33% were attendants, 11% were doctors and 11% were
      technicians. On source analysis, 23, 15 and 12 were positive for Hepatitis B
      surface antigen (HBsAg), human immunodeficiency virus (HIV) and hepatitis C virus
      (HCV), respectively. Immediate action following potential exposure included
      washing the wound with soap and water, encouraging bleeding and reporting the
      incident to the emergency room. Analysis of the source of injuries revealed that
      known sources accounted for 254 injuries, and unknown sources from garbage bags
      and Operating Theatre instruments accounted for 126 injuries. Most needlestick
      injuries occurred during intravenous line insertion (N=112), followed by blood
      collection (N=69), surgical blade injury (N=36) and recapping needles (N=36).
      Immediate postexposure prophylaxis (PEP) for HCWs who sustained injuries with
      hepatitis-B-virus-positive patients included booster hepatitis B immunization for
      those positive for antiHBs. A full course of immunization with hepatitis B
      immunoglobulin was given to those who were antiHBs negative. All staff who
      sustained injury with HIV were given immediate antiretroviral therapy (AZT 600
      mg/day) for six weeks. Subsequent six-month follow-up showed zero seroconversion.

PMID- 15961185
TI  - Safe disposal and effective destruction of clinical wastes.

PMID- 15961187
TI  - The pathophysiology of brain edema in acute liver failure.
AB  - Brain edema leading to intracranial hypertension is a cause of death in acute
      liver failure (ALF). The pathogenesis of this unique complication has been
      investigated in man, in experimental models and in isolated cell systems. From
      this experience, an integrated view has emerged, pointing at several mechanisms
      that contribute to cerebral swelling; an osmotic derangement in astrocytes,
      changes in cellular metabolism as well as alterations of cerebral blood flow. The
      ability of mild hypothermia to counteract each of these changes in experimental
      systems has supported the organization of a clinical trial of mild cooling in
      this disease. Such an advance can be viewed as the clinical translation of 20
      years of research in this area.

PMID- 15961186
TI  - The agouti-related protein and its role in energy homeostasis.
AB  - The melanocortin system plays an important role in the regulation of energy
      homeostasis. The Agouti-related protein (AGRP) is a natural antagonist of the
      action of alpha-melanocyte stimulating hormone (alpha-MSH) at the melanocortin
      receptors (MCR). AGRP is upregulated by fasting while intracerebroventricular
      injections of synthetic AGRP lead to increased appetite and food intake.
      Transgenic mice overexpressing AGRP are also hyperphagic and eventually become
      obese. AGRP is, therefore, a significant regulator of energy balance and a
      candidate gene for human fatness. Indeed, humans with common single nucleotide
      polymorphisms (SNPs) in the promoter or the coding region are leaner and
      resistant to late-onset obesity than wild-type individuals. AGRP is also
      expressed in the periphery. Recent studies show that AGRP in the adrenal gland is
      upregulated by fasting as much as it is in the hypothalamus. These data open up
      the possibility for a wider role by AGRP not only in food intake but also in the
      regulation of energy balance through its actions on peripheral tissues. This
      review summarizes recent advances in the biochemical and physiological properties
      of AGRP in an effort to enhance our understanding of the role this powerful
      neuropeptide plays in mammalian energy homeostasis.

PMID- 15961188
TI  - Alzheimer's lymphocytes are resistant to ultraviolet B-induced apoptosis.
AB  - In the present pilot investigation, the susceptibility of T-lymphocytes from
      Alzheimer's disease (AD) subjects (n=22) and aged-matched, non-demented controls
      (CNT) (n=12) was examined with ultraviolet (UV) B light-induced apoptosis in
      vitro. The basal apoptotic ratios were similar in both groups. However, the AD
      lymphocytes displayed significantly (p<0.0001) lower apoptotic levels than those
      of the CNT lymphocytes at all of the applied UVB exposure doses (100, 200 and 300
      mJ/cm(2)). These observations indicate that AD lymphocytes are more resistant
      than CNT lymphocytes to UVB irradiation.

PMID- 15961189
TI  - Prevention of age-related dysregulation of calcium dynamics by estrogen in
      neurons.
AB  - To determine the impact of aging and 17beta-estradiol on neuronal Ca2+
      homeostasis, intracellular Fura-2 Ca2+-imaging was conducted during 20-pulses of
      glutamate in hippocampal neurons cultured from embryonic (E18), middle-age (10
      months) and old (24 months) rat brain. Marked age-related differences in
      intracellular Ca2+ ([Ca2+]i) homeostasis and striking regulation by 17beta
      estradiol were seen. Embryonic neurons exhibited the greatest capacity to
      regulate Ca2+ homeostasis followed by middle-age neurons. In old neurons, the
      first peak [Ca2+]i was substantially greater than at other ages and the return to
      baseline Ca2+ rapidly dysregulated with an inability to restore [Ca2+]i following
      the first glutamate pulse which persisted throughout the 20 pulses. 17beta
      Estradiol pretreatment of old neurons profoundly attenuated the peak [Ca2+]i rise
      and delayed the age-associated dysregulation of baseline [Ca2+]i, normalizing
      responses to those of middle-age neurons treated with estradiol. The efficacy of
      17beta-estradiol extended below 10 pg/ml with full protection against toxicity
      from glutamate and Abeta (1-40). These results demonstrate age-associated
      dysregulation of [Ca2+]i homeostasis which was largely prevented by 17beta
      estradiol with implications for estrogen/hormone therapy.

PMID- 15961190
TI  - Age effects on atrophy rates of entorhinal cortex and hippocampus.
AB  - The effects of age, subcortical vascular disease, apolipoprotein E (APOE)
      epsilon4 allele and hypertension on entorhinal cortex (ERC) and hippocampal
      atrophy rates were explored in a longitudinal MRI study with 42 cognitively
      normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC,
      hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes
      were assessed on MR images. Age was significantly associated with increased
      atrophy rates of 0.04+/-0.02% per year for ERC and 0.05+/-0.02% per year for
      hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with
      presence of lacunes, in addition to age. WMH, APOE epsilon4 and hypertension had
      no significant effect on atrophy rates. In conclusion, age and presence of
      lacunes should be taken into consideration in imaging studies of CN subjects and
      AD patients to predict AD progression and assess the response to treatment
      trials.

PMID- 15961191
TI  - QSAR study on carbonic anhydrase inhibitors: water-soluble sulfonamides
      incorporating beta-alanyl moieties, possessing long lasting-intra ocular pressure
      lowering properties--a molecular connectivity approach.
AB  - A QSAR study on a series of carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, and
      more precisely on water-soluble sulfonamides incorporating beta-alanyl moieties,
      possessing long lasting intra-ocular pressure lowering properties, was carried
      out using a series of distance-based topological indices. The regression analysis
      has shown that out of the pool of topological indices used, the 1chi (first-order
      Randic connectivity index) is the best one for modeling CA inhibitory properties
      against all three investigated isozymes, the cytosolic CA I, CA II and the
      membrane-bound CA IV, and that excellent results are obtained in multiparametric
      regressions. The results are critically discussed on the basis of statistical
      parameters.

PMID- 15961192
TI  - Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5
      diarylpyrazoles to validate the modified pharmacophore.
AB  - Diverse analogs of 1,5-diarylpyrazoles having 3-hydroxymethyl-4-sulfamoyl
      (SO2NH2)/methyl sulfonyl (SO2Me)-pheny group at N1 were synthesized and evaluated
      for their in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The SAR
      study mainly involved the variations at positions C-3, C-5 and N1 of the pyrazole
      ring. Several small hydrophobic groups at/around position-4 of C-5 phenyl, viz.
      3,4-dimethylphenyl analog 9, 3-methyl-4-methylsulfanylphenyl analog 14 and 2,3
      dihydrobenzo[b]thiophenyl analog 17, exhibited impressive COX-2 inhibitory
      potency. In general, the sulfonamide analogues with a CHF2 at C-3 were found to
      be more potent than those having a CF3 group. The three dimensional quantitative
      structure activity relationship comprising comparative molecular field analysis
      (3D-QSAR-CoMFA) afforded the models with high predictivity which further
      validated the acceptance of hydroxymethyl (CH2OH) group in the hydrophilic pocket
      of the COX-2 enzyme.

PMID- 15961193
TI  - [Osteo-articular tuberculosis and postpartum: a casual association?].
AB  - INTRODUCTION: Most cases of active tuberculosis in France are due to a recurrence
      of latent tuberculosis. It seems that immunorestitution during the postpartum can
      contribute to the return of latent tuberculosis. EXEGESIS: We report three
      observations of Mycobacterium tuberculosis osteo-articular infections (two Pott's
      diseases and one sterno-clavicular arthritis) occurring during the postpartum of
      women non infected by HIV. Two patients need a surgical treatment. The response
      to standard tuberculous treatment was favourable and all patients were cured.
      CONCLUSION: One must consider osteo-articular tuberculosis when a patient is
      suffering from osseous pains not proving reliable during the postpartum. We must
      remind ourselves of the relationships between tuberculosis and postpartum as well
      as the necessity to the threat both mother and child. Additional epidemiological
      studies should be realised. It appears necessary to increase in France measures
      for tracking tuberculosis in particularly about the latent forms.

PMID- 15961194
TI  - Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine
      against ricin.
AB  - Ricin toxin is a plant-derived ribosome inactivating protein (RIP) of
      extraordinary toxicity. Vaccination using ricin toxoid or its A chain (RTA) is
      protective in animals but both vaccines have two potential toxicities, RIP and
      vascular leak syndrome (VLS). Previously we described three recombinant RTA
      constructs from which both toxicities were eliminated by site-specific mutations.
      One mutant, V76M/Y80A, RiVax, has now been further characterized for
      immunogenicity and toxicity in animals. We have found that RiVax is safe at doses
      of at least 8 mg in mice, 800-fold higher than the protective dose, and induces
      neutralizing antibodies in both mice and rabbits.

PMID- 15961195
TI  - Indications of limited altered gene expression in Pinus sylvestris trees from the
      Chernobyl region.
AB  - To evaluate the consequences of irradiation on the vegetation of the Chernobyl
      region, gene expression was compared in morphologically normal and dwarf needles
      from the same Pinus sylvestris trees in a region where the absorbed dose was 3-5
      Gy. To compare the levels of gene expression, arrays consisting of 373 Pinus
      taeda cDNAs were hybridized with labeled cDNA derived from normal and dwarf
      needles of P. sylvestris. Twelve genes were significantly (P<0.01) up- or down
      regulated between normal and dwarf needles for all five trees taken together.
      Five of these, related to stress or development, were up- or down-regulated 1.25
      1.7-fold in the dwarf needles. There were no significant differences in (137)Cs
      content in the normal and dwarf needles, or in elongation growth rate of
      seedlings raised under controlled conditions from seed derived from trees in the
      region that had received a radiation dose over the range 2-12 Gy.

PMID- 15961196
TI  - Data assimilation for short range atmospheric dispersion of radionuclides: a case
      study of second-order sensitivity.
AB  - This article presents the application of variational data assimilation to a
      simple Gaussian plume model for radionuclides. Adjoint modeling is applied to the
      model in order to minimize discrepancies between contamination observations and
      model outputs. The interest of such an approach is to get a better estimation of
      some parameters such as emissions or dispersion parameters. A second-order
      analysis is also performed to assess the sensitivity of the optimized parameters
      to some poorly known parameters. Sensitivity with respect to network design is
      also done.

PMID- 15961197
TI  - Application of the luminescence single-aliquot technique for dose estimation in
      the Marmara Sea.
AB  - The aim of this study is to obtain the equivalent dose, which is the important
      quantity for all the studies related to the use of luminescence in dating
      sediments. Recent advances in luminescence dating have led to increasing
      application of the technique to sediment from the depositional environmental
      samples. The sample used in this study is the active main fault sample that was
      collected from the Sea of Marmara in NW Turkey. Equivalent dose was measured
      using both the multiple-aliquots and the single-aliquot techniques. In this study
      single aliquot regeneration on additive dose (SARA) procedure was also used. The
      result obtained was not in agreement with the results evaluated from the multiple
      aliquots procedure. So a simple modification was suggested for SARA procedure. In
      our modified procedure the calculated dose (D) values were obtained by using the
      additive dose protocol instead of regeneration protocol.

PMID- 15961199
TI  - Attitude of a group of Belgian stakeholders towards proposed agricultural
      countermeasures after a radioactive contamination: synthesis of the discussions
      within the Belgian EC-FARMING group.
AB  - In the case of radioactive contamination of the environment with an impact on the
      food chain, the remediation strategy will not only be based on scientific
      knowledge and technical experience, but will also be dictated by peculiarities of
      the country. These characteristics include the agro-industrial structure, the
      local and international economical contexts and the political configuration
      including the distribution of responsibilities and competencies. This paper
      identifies and illustrates the most relevant characteristics of the Belgian
      agricultural system and political environment; it also describes the past
      experience with food chain contamination, which is expected to influence the
      attitude of Belgian stakeholders, who would be involved in the setting up of
      countermeasure strategies for maintaining agricultural production and food
      safety. The picture drawn explains why several countermeasures aiming to reduce
      the contamination in food products, although scientifically sound and technically
      feasible, are hardly acceptable or even not acceptable at all, to the
      stakeholders.

PMID- 15961200
TI  - Stakeholder involvement in nuclear crisis management in Greece.
AB  - The setting up of the Greek Stakeholders Group in the framework of the EC Food
      and Agriculture Restoration Management Involving Networked Groups (FARMING)
      project is described. The Group included members from more than 20 governmental
      and non-governmental organisations, having interest and/or responsibilities in
      the management of a crisis following a nuclear accident. The stakeholders, during
      their meetings in 2002, discussed the agricultural countermeasures and rural
      waste disposal options which have been compiled by the EC Sustainable Restoration
      and Long-Term Management of Contaminated Rural, Urban and Industrial Ecosystems
      (STRATEGY) project. All stakeholders agreed that the most preferable were those
      options that ensure public acceptance, minimise environmental impact and maintain
      farming practices and acceptable living and working conditions. Their views are
      synoptically presented along with the major conclusions from the stakeholders
      meetings regarding nuclear crisis management.

PMID- 15961201
TI  - Morbidity at the iliac crest donor site following bone grafting of the cleft
      alveolus.
AB  - We retrospectively analysed all cases of iliac crest bone graft harvest for
      secondary grafting of the cleft alveolus during an 11-year period. The case notes
      were reviewed and postal questionnaires sent to all patients. Of 73 consecutive
      patients, 57 (78%) were male, and the mean (S.D.) age at operation was 10 (1)
      years. A completed questionnaire was received from 72 patients (99%). The median
      stay in hospital was 3 days (range 2-5). The median time until the child could
      walk "normally" was 7 days (range 0-56). Thirty-seven patients (51%) had a
      postoperative limp, which resolved after a median of 7 days (range 3-56). There
      were two (3%) superficial donor site infections. The median length of scar was
      60mm (range 40-100) and patient satisfaction was high, with a median visual
      analogue scale of 9/10 (range 2-10). Harvesting bone from the iliac crest for
      alveolar bone grafting is well tolerated by patients, has few important
      complications, and gives an aesthetically acceptable scar at the donor site.

PMID- 15961202
TI  - Biomechanical background and clinical observations of rotational malalignment in
      TKA: literature review and consequences.
AB  - Malalignment, in particular femoral component malrotation, is a commonly accepted
      failure mode in total knee arthroplasty. The general objective of this paper is
      twofold: firstly, it accentuates clinical observations of the effects of
      rotational malalignment in total knee arthroplasty. Secondly, it discusses the
      relevant parameters of existing knee joint models with regards to rotational
      malalignment and its biomechanical background, thereby setting a basis for future
      studies. To summarise, when modelling malalignment in total knee arthroplasty,
      the following aspects should be considered: Friction between the implant
      components, ligamentous and capsular structures, deformable body to model the PE
      inlay, and an in vivo validation of the model. Because of the large variance in
      anthropometrical data between individuals, future knee joint models should also
      incorporate individual data.

PMID- 15961203
TI  - Bone-cement interface of the glenoid component: stress analysis for varying
      cement thickness.
AB  - BACKGROUND: Although shoulder arthroplasty is an accepted treatment for
      osteoarthritis, loosening of the glenoid component, which mainly occurs at the
      bone-cement interface, remains a major concern. Presently, the mechanical effect
      of the cement mantel thickness on the bone-cement interface is still unclear.
      METHODS: Finite element analysis of a prosthetic scapula was used to evaluate the
      effect of cement thickness on stresses and micromotions at the bone-cement
      interface. The glenoid component was all-polyethylene, keeled and flat back.
      Cement mantel thickness was gradually increased from 0.5 to 2.0 mm. Two
      glenohumeral contact forces were applied: concentric and eccentric. Two extreme
      cases were considered for the bone-cement interface: bonded and debonded.
      FINDINGS: Within cement, stress increased as cement thickness decreased, reaching
      the fatigue limit below 1.0 mm. Bone stress was below its ultimate strength and
      was minimum between 1.0 and 1.5mm. Interface stress was close to the interface
      strength, and also minimum between 1.0 and 1.5 mm. Both the decentring of the
      load and the debonding of the interface increased the stress. INTERPRETATION: A
      cement thinning weakens the cement, but also the bone-cement interface, along the
      back-keel edges. Conversely, a cement thickening rigidifies the cemented implant,
      consequently increasing interfacial stresses and micromotions. To avoid both
      excessive cement fatigue and interface failure, an ideal cement thickness has
      been identified between 1.0 and 1.5 mm.

PMID- 15961204
TI  - Rh proteins: key structural and functional components of the red cell membrane.
AB  - Rh (Rhesus) proteins (D, CcEe) are expressed in red cells (RBC) in association
      with other membrane proteins (RhAG, LW, CD47 and GPB). By interacting with the
      spectrin-based skeleton through protein 4.2 and ankyrin, the Rh complex
      contributes to the maintenance of the mechanical properties of the erythrocyte
      membrane. The RH system is one of the most immunogenic and polymorphic human
      blood group system. Molecular basis of most Rh phenotypes, including the Rh(null)
      phenotype associated with hemolytic anemia, have been determined. The
      demonstration that the RHD-positive locus is composed of the RHD and RHCE genes,
      whereas the RHD gene is deleted in most RhD-negative individuals, allowed fetal
      RhD genotyping by non-invasive PCR assays for antenatal diagnosis of pregnancy at
      risk for Rh hemolytic disease of the newborn. In mammals, the Rh protein family
      includes two non-erythroid members, RhBG and RhCG, mainly expressed in liver and
      kidney, two organs specialized in ammonia genesis and excretion. Functional
      analyses in heterologous systems revealed that RhAG, RhBG and RhCG can mediate
      ammonium (NH(3) and/or NH(4)(+)) transport across the cell membrane and might
      represent mammalian specific ammonium transporters. Furthermore, recent studies
      performed in human and murine red blood cells (RBC) indicate that RhAG
      facilitates CH(3)NH(2)/NH(3) movement across the membrane and represents a
      potential example of gas channel. The crystallographic structure of the bacterial
      ammonia channel AmtB and functional studies showing that AmtB conducts NH(3) into
      reconstituted vesicles is fully consistent with these latter studies. In RBCs,
      RhAG may transport NH(3) to detoxifying organs like kidney and liver and with non
      erythroid tissues orthologs may contribute to regulation of the acid-base
      balance.

PMID- 15961205
TI  - Treatment of insomnia in older adults.
AB  - Insomnia outcome studies from the last 15 years show consistent success for
      behavioral treatment with older adults. The present review of evaluation and
      treatment covers the effects of aging on ability to sleep, the insomnia
      classification system, the treatment efficacy database, and critical outcome
      research methodology. Clinical trial methodology with older adults includes
      familiar challenges; for example, the need for placebo controls, and frequent
      failures to document the adequacy of treatment implementation. Recommendations
      for improving methodology are offered. A new review of treatment for primary
      insomnia in older adults shows strong improvement and consistent results for
      popular behavioral treatments. Older adult clinical trials show proven efficacy
      of behavioral treatment for primary insomnia, efficacy for secondary insomnia,
      and efficacy for insomnia associated with hypnotic dependency.

PMID- 15961206
TI  - Ruling in and ruling out: implications of molecular genetic diagnoses for disease
      classification.
AB  - We report on a qualitative analysis of interviews with 14 genetic counsellors in
      Ontario, Canada about the implications of developments in molecular genetic
      knowledge for disease definition and classification. Genetic counsellors express
      a restrained set of hopes and expectations about the utility of genetic
      diagnoses. They identify several limitations faced by available genetic tests,
      limitations that constrain the significance of genetic information in disease
      identification and clinical management. Yet they also emphasize the fundamental
      nature of genetic information, its decisive role in specifying disease causation,
      and its significance for disease classification. The decisive nature of genetic
      information means that, in some cases, genetic tests foster change in disease
      categories. Diseases are redefined by the "ruling in" of atypical cases
      demonstrating a broader spectrum of clinical effects, or the "ruling out" of
      typical cases with classic clinical presentations that are better assigned to
      other (or no) causes. These redefinitions can be profoundly consequential,
      producing several kinds of uncertainty: What do we call this state of being? How
      do we manage it clinically? And, what are the social entitlements of individuals
      in this state? Though limited today, such complex effects can be expected to
      increase, alongside the growing diagnostic power of molecular genetics.

PMID- 15961207
TI  - The effect of chronic selective serotonin reuptake inhibitor treatment on
      serotonin 1B receptor sensitivity and HPA axis activity.
AB  - The authors have investigated 5-HT 1B receptor function in prefrontal cortex and
      dorsal hippocampus as well as the HPA axis response after subchronic (24 h) and
      chronic (15 days) treatment with the SSRI citalopram. All experiments were
      carried out in presence of citalopram to prevent rapid resensitization of the 5
      HT(1B) receptors. Moreover, this more closely resembles the clinical situation.
      The concentration of citalopram was measured in both brain areas to ensure
      comparable levels in the different treatment groups. Using microdialysis, the
      authors found that under those conditions the effect of the 5-HT 1B receptor
      antagonists SB 224289 and the mixed 5-HT 1B/1D receptor antagonist GR 127935 on
      extracellular levels of 5-HT was unaltered by duration of treatment. Basal levels
      of 5-HT, however, were increased in the dorsal hippocampus following chronic
      treatment. In addition, plasma levels of the catecholamines adrenaline and
      noradrenaline and the HPA axis hormones ACTH and corticosterone were all
      decreased after chronic treatment.

PMID- 15961208
TI  - Direct-care staff body mass index in a state mental hospital: staff obesity may
      impair role modeling for patients.
AB  - INTRODUCTION: Direct-care staff at institutions providing long-term care serve as
      both caretakers and role models for their patients. The authors report a second
      study showing that major portions of such direct-care staff have significant
      problems themselves with overweight and obesity. This may be another changeable
      factor in the complex dynamics governing overweight and obesity among patients
      with chronic mental illness. METHOD: The authors recorded age, sex, and race, and
      measured height and weight during a typical 8-h shift among 50 direct-care staff
      at a long-term care psychiatric institution. Direct-care staff were defined as
      those members of the nursing staff who spent at least 4 h of their 8-h shift in
      direct contact with their patients. RESULTS: Of the 50 direct-care staff, 44 were
      black females. The authors focused on this subgroup in our report. These 44 black
      female direct-care staff had a mean body mass index (BMI) of 33.8+/-8.3 kg/m(2)
      and 27 (61.4%) were obese. Six of them (13.6%) were morbidly obese. CONCLUSIONS:
      Overweight and obesity may be a greater problem for staff providing care for
      patients with chronic mental illness than for the patients themselves. The
      authors believe studies are needed to test the hypothesis that staff obesity may
      impair staff ability to help obese patients lose weight. In our two studies to
      date, black women functioning as direct-care staff were highly vulnerable to
      overweight and obesity.

PMID- 15961209
TI  - Regulation by allergens of chemokine receptor expression on in vitro-generated
      dendritic cells.
AB  - Immature dendritic cells (DCs) derived from CD34+ progenitor cells or peripheral
      monocytes, are used as in vitro sensitization models in many chemical allergen
      treatment studies. During the sensitization, DCs follow maturation process and
      gain the capacity to migrate to lymph nodes where they stimulate T cells.
      Chemokine receptor allows DCs to migrate along chemotactic gradients. In this
      work, we used immature DCs from peripheral monocytes to evaluate the influence of
      allergens on chemokine receptor and surface-marker expression. We tested the
      sensitizers dinitrochlorobenzene, Bandrowski's base, and coumarin, as well as the
      tolerogen dichloronitrobenzene, the irritant sodium dodecyl sulfate and the
      solvent dimethyl sulfoxide. All skin sensitizers up-regulated the co-stimulatory
      molecule CD86 and increased the CD83+ cell population. No expression of the
      chemokine receptors CCR2, CCR3, CCR6, or CXCR5 was observed on DCs exposed to the
      tested chemicals. The strong allergen dinitrochlorobenzene slightly increased
      CCR7 expression on DCs but down-regulated CCR1 surface expression. CCR1 down
      regulation was not mediated by a classical maturation pathway, as it was
      unaffected by the corticosteroid dexamethasone.

PMID- 15961210
TI  - Meta-analytic review of event-related potential studies in post-traumatic stress
      disorder.
AB  - In recent years there has been an accumulation of studies that have utilized the
      measurement of event-related potentials (ERP) to examine the neuroelectric
      correlates of hypothesized alterations in information processing in persons with
      post-traumatic stress disorder (PTSD). The objective of this meta-analysis was to
      summarize the findings of ERP PTSD research, including studies that have examined
      P50 auditory sensory gating, augmenting-reducing P200, and P300 in target
      detection oddball tasks. The results suggest that persons with PTSD exhibit
      alterations in the amplitude and latency of ERP within these paradigms that
      support the hypothesis that changes in information processing can accompany PTSD.
      The results were also consistent with recent cognitive neuropsychological
      findings in PTSD research.

PMID- 15961211
TI  - Motivated executive attention--incentives and the noise-compatibility effect.
AB  - The motivational context is an important variable in experimental research. The
      present study investigates the effects of reward and punishment on performance in
      a noise-compatibility-task [Eriksen, B.A., Eriksen, C.W., 1974. Effects of noise
      letters upon the identification of a target letter in a nonsearch task.
      Perception and Psychophysics 16 (1), 143-149]. Flanking distractors indicated a
      response, which was identical, undefined, or opposite to the appropriate response
      indicated by the central target. At the beginning of each trial a cue specified
      positive, negative or no reinforcement in order to elicit three different
      motivational states: approach, avoidance and a non-reinforced neutral state.
      Fifty-three subjects (aged 20-27 years) participated. Incompatibility effects on
      reaction times and percentage errors were analysed as a function of motivational
      state, as were the effects on two ERPs, the lateralised readines potential (LRP)
      and the N2. Error and LRP data showed effects of reinforcement only when
      incompatible distractors were present, which indicates that controlled processing
      depends on the motivational context. In contrast to previous findings, the N2 was
      not found to depend on response conflict.

PMID- 15961212
TI  - Hemodynamic, hemostatic, and endothelial reactions to psychological and physical
      stress in coronary artery disease patients.
AB  - Episodes of psychological and physical stress may elicit thrombotic cardiac
      events, such as myocardial infarction. These events are triggered when there are
      concurrent hemodynamic, hemostatic, and endothelial abnormalities. Hemodynamic,
      hemostatic, and endothelial reactions of 72 (15 women, 57 men) coronary artery
      disease patients to psychological and physical stress were examined. Blood
      pressure, electrocardiography, and impedance cardiography were recorded during
      rest, mental arithmetic, and exercise. Blood was collected, via catheter, at rest
      and after each task. Mental arithmetic elicited increases in blood pressure,
      heart rate, cardiac output, and cardiac contractility, but no consistent changes
      in hemostatic and endothelial markers. In contrast, exercise, in addition to
      increasing blood pressure, heart rate, cardiac output, cardiac contractility, and
      lowering peripheral resistance, elicited increases in plasma viscosity,
      hematocrit, platelets, and tissue plasminogen activator together with a decrease
      in plasminogen activator inhibitor. This pattern of hemodynamic, hemostatic, and
      endothelial reactions suggests that acute psychological and physical stress
      influence the thrombotic system differently in these high risk patients. Future
      research is needed to investigate how these stress responses are prospectively
      related to acute cardiac events.

PMID- 15961213
TI  - Blood pressure reactivity to stress is better for people who recently had penile
      vaginal intercourse than for people who had other or no sexual activity.
AB  - Penile-vaginal intercourse (PVI) but not other sexual behavior is associated with
      better psychological and physiological function. I examined the relationship of
      sexual behavior patterns to blood pressure (BP) and its reactivity to stress
      (public speaking and verbal arithmetic). For a fortnight, 24 women and 22 men
      used daily diaries to record PVI, masturbation, and partnered sexual behavior in
      the absence of PVI. Persons who reported PVI (but no other sexual activities) had
      better stress response (less reactivity and/or lower baseline levels) than
      persons reporting other or no sexual behaviors. Persons who only masturbated or
      had partnered sex without PVI had 14 mmHg more systolic BP reactivity than those
      who had PVI but not the other behaviors. Many variables were examined but failed
      to confound the observed relationships. The magnitude of the sexual behavior
      effect on BP reactivity is greater than of other factors in the literature. These
      findings add to the research corpus on the benefits of PVI (differentiated from
      other sexual activities).

PMID- 15961214
TI  - Head pushing versus reverse breech extraction in cases of impacted fetal head
      during Cesarean section.
AB  - OBJECTIVE: To compare maternal and neonatal morbidity associated with two methods
      to extract the impacted fetal head during Cesarean delivery. STUDY DESIGN: We
      retrospectively analyzed cases with difficult extraction of the impacted fetal
      head during Cesarean section. We compared maternal and neonatal outcomes between
      cases that were delivered by head extraction following pushing through the vagina
      ('push' method) and those that were delivered by the reverse breech technique
      ('pull' method). RESULTS: We reviewed 3105 Cesarean section reports. Difficult
      extraction necessitating the 'push' or 'pull' methods was noted in 48 (1.5%)
      instances. Women that were delivered by the 'pull' method had significantly lower
      rate of postpartum fever (5% versus 46%; odds ratios, 0.06; 95% confidence
      intervals, 0.007-0.51) and extensions of the uterine incision (15% versus 50%;
      odds ratio, 0.17; 95% CI, 0.04-0.74) compared to those that were delivered by the
      'push' method. Neonatal outcomes were good in all cases. CONCLUSIONS: In cases
      with difficult extraction of the impacted fetal head during Cesarean section,
      'pull' method may result in lower maternal morbidity compared to the traditional
      'push' method.

PMID- 15961215
TI  - Pressure-induced phase transitions of lipid bilayers observed by fluorescent
      probes Prodan and Laurdan.
AB  - The fluorescence spectra of 6-propionyl-2-(dimethylamino)naphthalene (Prodan) and
      6-dodecanoyl-2-(dimethylamino)naphthalene (Laurdan) in bilayer membranes of 1,2
      distearoylphosphatidylcholine (DSPC) were observed as a function of pressure at
      constant temperature. The emission spectra of Prodan and Laurdan varied with the
      pressure-induced states of bilayer membranes. The maximum emission wavelength
      (lambda(max)) of Prodan characteristic of the liquid crystalline (L(alpha)),
      lamellar gel (L(beta)') and pressure-induced interdigitated gel (L(beta)I) phases
      of the DSPC bilayer was 480, 440 and 500 nm, respectively. On the other hand, the
      lambda(max) of Laurdan characteristic of the L(alpha) and L(beta)' phases was 480
      and 440 nm in a similar manner as Prodan probe. However, no change in the
      lambda(max) was observed in spite of the occurrence of the interdigitation of
      bilayer. Since the lambda(max) reflects the solvent property around the probe
      molecules, we could speculate about the location of fluorescent probe in the
      bilayer membranes. In the L(alpha) phase the same chromophore group of Prodan and
      Laurdan probes distributes around phosphate group of lipid (i.e., polar region).
      The transformation of bilayer into the L(beta)' phase causes the Prodan and
      Laurdan molecules to move into the glycerol backbone (i.e., less polar) region.
      In the ripple gel (P(beta)') phase, the emission spectrum of Prodan shows a broad
      peak at about 480 nm and a shoulder around 440 nm, which means that the Prodan
      molecules are widespread over the wide range from the glycerol backbone to the
      hydrophilic part of bilayer. The P(beta)'/L(beta)I phase transition causes the
      Prodan molecule to squeeze out from the glycerol backbone region and to move the
      hydrophilic region near the bilayer surface. Contrarily, the Laurdan molecule was
      not squeezed out from the glycerol backbone region because the long acyl chain of
      Laurdan serves as an anchor in the hydrophobic core of bilayer. The ratio of
      fluorescence intensity of Prodan at 480 nm to that at 440 nm, F(480)/F(440), is
      available to observation of bilayer phase transitions. The plot of F(480)/F(440)
      versus pressure seems to be useful for the recognition of bilayer phase
      transition, especially the bilayer interdigitation.

PMID- 15961216
TI  - Correlation character of ionic current fluctuations: analysis of ion current
      through a voltage-dependent potassium single channel.
AB  - The gating of ion channels has widely been modeled by assuming the transition
      between open and closed states is a memoryless process. Nevertheless, the
      statistical analysis of an ionic current signal recorded from voltage dependence
      K(+) single channel is presented. Calculating the sample auto-correlation
      function of the ionic current based on the digitized signals, rather than the
      sequence of open and closed states duration time. The results provide evidence
      for the existence of memory. For different voltages, the ion channel current
      fluctuation has different correlation attributions. The correlations in data
      generated by simulation of two Markov models, on one hand, auto-correlation
      function of the ionic current shows a weaker memory, after a delayed period of
      time, the attribute of memory does not exist; on the other hand, the correlation
      depends on the number of states in the Markov model. For V(p)=-60 mV pipette
      potential, spectral analysis of ion channel current was conducted, the result
      indicates that the spectrum is not a flat spectrum, the data set from ionic
      current fluctuations shows considerable variability with a broad 1/f -like
      spectrum, alpha=1.261+/-0.24. Thus the ion current fluctuations give information
      about the kinetics of the channel protein, the results suggest the correlation
      character of ion channel protein nonlinear kinetics regardless of whether the
      channel is in open or closed state.

PMID- 15961217
TI  - Urodynamic effect of intravesical resiniferatoxin in patients with neurogenic
      detrusor overactivity of spinal origin: results of a double-blind randomized
      placebo-controlled trial.
AB  - OBJECTIVES: To access by a placebo-controlled randomized clinical trial the
      effect of intravesical resiniferatoxin on the urodynamic parameters of patients
      with neurogenic detrusor overactivity (NDO) of spinal origin. METHODS: Twenty
      eight patients with spinal NDO were randomised to receive intravesically 50 nM
      resiniferatoxin dissolved in 10% ethanol in saline (RTX group) or only the
      vehicle solution (placebo group). Filling cystometries were obtained in each
      patient at 1 month and 1 week before and at 1 and 3 months after treatment. In a
      visual analog scale patients were asked to estimate the discomfort induced by
      treatment. Patients were also persuaded to fill a micturition chart during the 3
      days preceding each cystometry. RESULTS: The RTX and placebo groups were
      homogeneous in what respects the volume to first involuntary detrusor contraction
      (FDC, 143+/-95 ml and 115+/-58 ml, respectively, p=0.3) and maximal cystometric
      capacity (MCC, 189+/-99 ml and 198+/-111 ml, respectively, p=0.8). At the end of
      the study, mean FDC and MCC in the RTX group, 184+/-93 ml and 314+/-135 ml,
      respectively were significantly higher than in the placebo group, 115+/-61 ml
      (p=0.03) and 204+/-92 ml (p=0.02). In the visual analogue scale discomfort caused
      by treatment was similar. Only 10 patients in the RTX group and 6 patients in the
      placebo group completed adequately the micturition chart. Mean frequency and
      urinary incontinence decreased significantly only in the RTX group. CONCLUSIONS:
      Intravesical RTX is effective in increasing bladder capacity in spinal NDO
      patients. Such increment might contribute to decrease urinary frequency and
      incontinence of these patients.

PMID- 15961218
TI  - Prostatic intraepithelial neoplasia (PIN): importance and clinical management.

PMID- 15961219
TI  - Development and validation of a risk score for somatic erectile dysfunction:
      combined results from three cross-sectional surveys.
AB  - OBJECTIVES: Some men with erectile dysfunction (ED) have difficulties discussing
      their condition with their physicians. Existing screening and diagnostic tools
      for ED often require the administration of personal questions regarding the
      condition. We present a simple risk score to estimate the individual likelihood
      of somatic ED, based on age and existing health conditions. METHODS: Data from
      the Cologne Male Survey (n = 4396) were used to develop a multivariable logistic
      regression model for the individual ED likelihood. The regression equation was
      both internally and externally validated using data from a national study (Berlin
      study) and a multinational cross-sectional study (MALES study). RESULTS: A final
      regression equation including age, pelvic surgery, diabetes mellitus, arterial
      circulatory disorder, heart disease, smoking, and hypertension reached an area
      under the receiver operating characteristic curve of 0.84 (0.5 means random and
      1.0 perfect discrimination). Internal validation did not indicate any relevant
      overfit and the external validation results (national data: AUC = 0.75;
      multinational data: AUC = 0.67) are similar to those of other popular risk
      scores. CONCLUSIONS: The validated ED risk score developed from the regression
      equation can be used as a screening tool to identify patients who are at a high
      risk of somatic ED. This tool can facilitate entering into discussions between
      physicians and patients regarding erectile function.

PMID- 15961221
TI  - Azadirachta indica (Neem) leaf powder as a biosorbent for removal of Cd(II) from
      aqueous medium.
AB  - A biosorbent, Neem leaf powder (NLP), was prepared from the mature leaves of the
      Azadirachta indica (Neem) tree by initial cleaning, drying, grinding, washing to
      remove pigments and redrying. The powder was characterized with respect to
      specific surface area (21.45 m2g(-1)), surface topography and surface functional
      groups and the material was used as an adsorbent in a batch process to remove
      Cd(II) from aqueous medium under conditions of different concentrations, NLP
      loadings, pH, agitation time and temperature. Adsorption increased from 8.8% at
      pH 4.0 to 70.0% at pH 7.0 and 93.6% at pH 9.5, the higher values in alkaline
      medium being due to removal by precipitation. The adsorption was very fast
      initially and maximum adsorption was observed within 300 min of agitation. The
      kinetics of the interactions was tested with pseudo first order Lagergren
      equation (mean k(1)=1.2x10(-2)min(-1)), simple second order kinetics (mean
      k2=1.34x10(-3) gmg(-1)min(-1)), Elovich equation, liquid film diffusion model
      (mean k=1.39x10(-2)min(-1)) and intra-particle diffusion mechanism. The
      adsorption data gave good fits with Langmuir and Freundlich isotherms and yielded
      Langmuir monolayer capacity of 158mgg(-1) for the NLP and Freundlich adsorption
      capacity of 18.7 Lg(-1). A 2.0 g of NLP could remove 86% of Cd(II) at 293 K from
      a solution containing 158.8 mg Cd(II) per litre. The mean values of the
      thermodynamic parameters, DeltaH, DeltaS and DeltaG, at 293 K were -73.7 kJmol(
      1), -0.24 Jmol(-1)K(-1) and -3.63 kJmol(-1), respectively, showing the adsorption
      process to be thermodynamically favourable. The results have established good
      potentiality for the Neem leaf powder to be used as a biosorbent for Cd(II).

PMID- 15961220
TI  - Cytotoxicity of PAI2, C595 and Herceptin vectors labeled with the alpha-emitting
      radioisotope Bismuth-213 for ovarian cancer cell monolayers and clusters.
AB  - The vectors PAI2, C595 and Herceptin target the membrane-bound uPA, MUC1 and HER2
      antigens expressed by cancer cells, respectively. The expression of these
      receptors was tested in the ovarian cancer cell line OVCAR-3; MUC-1 was strongly
      expressed (3+), uPA moderately expressed (2+), but HER2 was negative (-). The
      alpha-emitting radionuclide Bismuth-213 was chelated with these targeting vectors
      to form alpha conjugates (ACs), the cytotoxicity of which were tested with OVCAR
      3 cells. The PAI2 and C595 ACs are highly cytotoxic to the ovarian monolayer
      cancer cells and cell clusters in a concentration-dependent fashion and cause
      morphological changes of treated cancer cells, inducing apoptosis. These ACs are
      potential candidates for the control of ovarian cancer at the minimum residual
      disease (MRD) stage.

PMID- 15961222
TI  - Simple empirical method for prediction of impact sensitivity of selected class of
      explosives.
AB  - A new approach is described in this work to predict impact sensitivity of a
      variety of polynitroaliphatics, polynitroaromatics and the explosives containing
      N-NO2. This paper introduces some simple correlations for prediction of impact
      sensitivity of C(a)H(b)N(c)O(d) explosives using a, b, c, d, molecular weight and
      structure information of the explosive. The new correlations are applied to test
      different polynitroaromatics, benzofuroxans and nitramines. The results are
      compared with experimental data and some models of complex quantum mechanics
      computation. Predicted impact sensitivities for 46 explosives have a root mean
      square (rms) of deviation from experiment of 24 cm, which show good agreement
      with respect to measured values as compared to five different quantum mechanical
      models. Impact sensitivities for 58 polynitroaliphatics and related explosives
      are also calculated, and have a rms deviation from experiment of 40 cm.

PMID- 15961223
TI  - The effect of citrate, oxalate, acetate, silicate and phosphate on stability of
      synthetic arsenic-loaded ferrihydrite and Al-ferrihydrite.
AB  - The effect of the organic species oxalate, citrate and acetate and the inorganic
      species silicate and phosphate on release of As(V) from synthetic arsenic-loaded
      ferrihydrite and Al-ferrihydrite in the pH range 4-8 was investigated. For
      ferrihydrite, the organic species increased %As(V) extraction in the order:
      acetate<oxalate<<citrate. In each case, the %As(V) extraction increased when
      acidity changed to pH's lower than 6, but remained unchanged when the pH
      increased from 6 to 8. For Al-ferrihydrite, the trend for %As release as a
      function of pH in the presence of acetate and oxalate was similar to that for
      ferrihydrite. However, unlike the ferrihydrite case, in the presence of citrate
      the %As extraction went through a minimum at pH 6. This is postulated to be
      related to the solubility equilibria of Al-ferrihydrite as a function of pH. The
      co-presence of silicate or phosphate with each of the organic species enhanced
      As(V) extraction in the order SiO3(2-)>PO4(3-). Competitive adsorption of the
      investigated organic and inorganic species on ferrihydrite and Al-ferrihydrite
      could explain the enhanced release of As(V) into solution. However,
      disproportionate adsorption of other species relative to amount of As(V) release
      occurs, suggesting that mechanisms other than competitive adsorption are also
      operative. The results could best be explained in terms of combination of
      competitive adsorption and processes involving pH-dependent dissolution of
      ferrihydrite/Al-ferrihydrite, formation of various complex ionic species
      involving Al(III), Fe(III), As(V), SiO3(2-), PO4(3-), OH-, H+ and organic
      species: acetate, oxalate and citrate.

PMID- 15961224
TI  - Process kinetics of inoculation composting of municipal solid waste.
AB  - A method was used to improve the composting efficiency by seeding with Inoculum A
      (a blend of Bacillus azotofixams, Bacillus megaterium and Bacillus
      mucilaginosus), Inoculum B (a blend of effective cellulolytic strains, i.e.
      Trichoderma koningii, Streptomyces cellulosae, and White-rot fungi), and Inoculum
      C (a mixture of Inoculum A and Inoculum B). There were four runs: the control run
      (not inoculated), Run A, Run B and Run C. During the runs, parameters such as
      temperature, O2, CO2 and H2S emissions, and microbial concentration were
      investigated to study the efficiencies of inoculation composting. The maximum
      oxygen uptake rates in the control run, Run A, Run B and Run C were calculated as
      0.22, 0.32; 0.28 and 0.34 mol/hkg while the corresponding total O2 quantities
      accumulated were 511.18, 684.57, 659.74 and 778.47 g/hkg, respectively. In
      addition, odorous gases were highly reduced by inoculation. In order to
      understand the mechanisms of inoculation composting process, two stages kinetics
      equations were developed from the viewpoint of microbial kinetics. These
      equations showed that, in the first stage, microbial concentration was the main
      limiting factor of the degradation rate. The degradation rates in control, Run A,
      Run B and Run C were 10.5, 13.61, 13.08, and 15.671 g/kgh, respectively. In the
      second stage, the degradation rate was mainly affected by substrate
      concentration. Although the degradation rates were at almost the same level for
      both with and without inoculation, inoculation could reduce the half velocity
      coefficient K(m) and in turn stabilize the composting products efficiently.
      Therefore, inoculation could improve the efficiency of the composting process.

PMID- 15961225
TI  - Photocatalytic degradation of Remazol Red F3B using ZnO catalyst.
AB  - The photocatalytic degradation of aqueous solution of a commercial azo-reactive
      textile dye, Remazol Red F3B, has been investigated in a batch slurry reactor, in
      the presence of ZnO catalyst using two different UV light sources emitting at 254
      nm and 365 nm. The effects of various process variables on degradation
      performance of the process have been investigated. The results showed that
      decolourization and total organic carbon (TOC) removal are both affected in the
      same manner by the solution pH in the pH range 6-10, showing maxima at pH 7 and
      pH 10. They are inversely related to the dye concentration, they increase in
      power-law with the light intensity. Decolourization is faster with 365 nm UV. TOC
      removal is not affected by UV wavelength in the initial period up to 20 min,
      after which it progresses faster under 365 nm UV radiation. These results
      indicate that the UV wavelength influences especially the degradation rate of the
      intermediate products generated during the initial period of the photocatalytic
      process. Finally, catalyst loading affects both efficiencies in the same trend,
      which are maximized at about 2 g/l catalyst loading.

PMID- 15961226
TI  - Degradation kinetics of TNT in the presence of six mineral surfaces and ferrous
      iron.
AB  - Trinitrotoluene (TNT), a nitroaromatic explosive, is a commonly encountered
      groundwater contaminant in the United States that can pose a human health risk,
      even at very low aqueous concentrations. This study describes the process
      characteristics of abiotic degradation of dissolved TNT in the presence of
      ferrous iron (Fe2+) and six different minerals-processes relevant to a more
      complete understanding of reduced iron technologies in TNT cleanup. Kinetic
      degradation batch reactions involving combinations of TNT, ferrous iron, six
      minerals with varying cation exchange capacity, and two pH buffers were
      performed. The rate of TNT degradation was quantified using high performance
      liquid chromatography (HPLC). Unbuffered reactions between TNT, Fe2+, and
      magnetite, pyrite, quartz, and goethite/quartz were insignificant. However,
      unbuffered reactions between TNT, Fe2+, and calcite and siderite proceeded
      rapidly to completion. The difference in reaction rates was attributable to the
      elevated pH in the presence of the latter minerals. For reactions performed in
      buffered systems with pH 7.4, degradation followed a second-order kinetics rate
      law. For reactions in buffered systems with pH 9.0, the reactions proceeded to
      completion almost instantaneously. The presence of the mineral solid surface was
      necessary for TNT reduction to proceed, with the most rapid reaction rates
      occurring in the presence of a suspected hydroxy solid phase that formed at high
      pH.

PMID- 15961227
TI  - Coexistence of salusin and vasopressin in the rat hypothalamo-hypophyseal system.
AB  - Salusins are two newly discovered TOR-related peptides consisting of 28 and 20
      amino acids and designated salusin-alpha and salusin-beta, respectively. Using
      immunohistochemistry techniques, salusin-like immunoreactivity was detected in
      the rat hypothalamo-neurohypophyseal tract and immunopositive cells were
      distributed in the suprachiasmatic, supraoptic and paraventricular nucleus. In
      the paraventricular nucleus, salusin-like immunoreactivity was observed both in
      parvocellular and magnocellular neurons. Many salusin-positive nerve fibers and
      their terminals were identified in the internal layer of the median eminence and
      posterior pituitary. Less intense salusin-positive staining of fibers and
      terminals was found in the suprachiasmatic nucleus and external layer of the
      median eminence. Dual immunostaining was performed to determine if salusin
      coexisted with vasopressin or oxytocin in the hypothalamus. Most of the salusin
      like immunoreactivity was detected in vasopressin- but not in oxytocin-containing
      neurons in these nuclei. The functional significance of the coexistence of
      salusin with vasopressin is discussed, including the possibility that salusin
      participates in the regulation of blood pressure.

PMID- 15961228
TI  - Limited protection of TAT-Bcl-X(L) against pneumolysin-induced neuronal cell
      death.
AB  - Severe brain damage in patients with pneumococcal meningitis is in part caused by
      the cytosolic pneumococcal protein pneumolysin. The devastating effect of this
      neurotoxin might be alleviated by interfering with the cell death pathways that
      it sets in motion. An important player in these pathways is Bcl-X(L), an
      antiapoptotic protein of the Bcl-2 family, which is neuroprotective in various in
      vitro and in vivo models of cell death. We investigated whether its membrane
      permeable form, the TAT-Bcl-X(L) fusion protein, is capable of protecting human
      SH-SY5Y neuroblastoma cells against pneumolysin-induced cell death. Under mild
      pneumolysin-induced neuronal injury, TAT-Bcl-X(L) increased cell viability
      significantly by approximately 40% (82.7 +/- 16.1% versus 70.0+/-8.2%; p = 0.04).
      When the cells were exposed to a more rigorous pneumolysin treatment, TAT-Bcl
      X(L) had no protective effects. This suggests the involvement of additional
      neuronal death pathways in pneumolysin-induced cell death, which are not
      controlled by Bcl-X(L). Therefore, Bcl-X(L), a promising therapeutic candidate
      for ischemia and neurodegenerative diseases, is only of partial efficacy in
      preventing the direct neurotoxicity of pneumolysin.

PMID- 15961229
TI  - Differential amygdala habituation to neutral faces in young and elderly adults.
AB  - Habituation is a highly adaptive property of the nervous system, which allows for
      the allocation of attention and other cognitive resources to more imperative
      environmental events. The amygdala is an important site of habituation in humans,
      but no studies to date have examined the effects of aging on amygdala
      habituation. Given the amygdala's role in evaluating the salience of a stimulus
      and initiating behavioral responses, the potential importance of amygdala
      habituation in aging may be far-reaching. Therefore, we assessed for differences
      in habituation in the amygdalae of healthy young and elderly adults during
      repeated presentations of neutral human faces using functional magnetic resonance
      imaging (fMRI). In addition, we evaluated the relationship between amygdala
      volume and habituation, to examine the effects of atrophy. Eighteen healthy young
      controls and 18 healthy elderly subjects were scanned with fMRI during viewing of
      repeatedly presented neutral human face stimuli. Significant fMRI signal
      decrement was observed across all subjects for early versus late face
      presentations. Analysis of group, condition, and hemisphere revealed a
      significant three-way interaction, with right greater than left habituation in
      the young, but left greater than right amygdala habituation in the elderly.
      Volumetric and correlational analyses demonstrated that amygdala volume is
      associated with habituation in the right, but not left, hemisphere. We conclude
      that, in healthy elderly adults, the amygdala retains its adaptive habituation
      response, but speculate that intrinsic changes in amygdala anatomy during aging
      may modulate its laterality.

PMID- 15961230
TI  - Phase contrast and DIC illumination for AFM hybrids.
AB  - High-resolution optical microscopy is an essential pre-requisite for life science
      force microscopy, particularly for applications in cell biology and medicine.
      Identification and validation of cells is typically established with techniques
      like phase contrast microscopy or differential interference contrast microscopy.
      The option to select or monitor individual cells online with such light
      microscopy techniques while performing atomic force microscopy (AFM) measurements
      is therefore extremely beneficial. Here, we report two conceptually different
      strategies to implement these light microscopy techniques in a fully functional
      AFM head at the ultimate resolution of the Abbe diffraction limit.

PMID- 15961231
TI  - Quantification of biopolymer filament structure.
AB  - The quantitative analysis of a polymer network is important for understanding its
      role in biological function. We developed a Matlab program to recognize and
      segment filaments in a 2-D image, and measure and describe the structure. Our
      algorithm improved the speed of the Lichtenstein Fiberscore segmentation
      algorithm by using matrix convolutions, compared filament length by the
      algorithms of Kulpa, Lichtenstein, and Kimura, and measured the number of
      branchpoints and Euler number. A user interface was added to easily manipulate
      algorithm parameters, select images, and visualize results. We used the program
      to compare the DNA biopolymer network of cystic fibrosis (CF) sputum with mucus
      from patients without respiratory problems. We also examined an image of fibrin.
      The images were taken with a laser scanning confocal microscope after staining
      the specimens with Yo-Yo-1. Computation using matrix convolutions reduced the
      execution time (Pentium III) of a 512 x 512 TIF image from 18 min to 15s. The
      Kimura length estimation appeared best at describing filament length because it
      varied least with filament orientation. The image of CF sputum showed increased
      filament length, more branchpoints, and more negative Euler number compared to
      the normal sample. These quantitative descriptions of the network can be
      correlated to material, mechanical, diffusion, or flow properties, physiological
      processes, or therapy.

PMID- 15961232
TI  - Characterization of the second internal transcribed spacer of ribosomal DNA of
      Calicophoron daubneyi from various hosts and locations in southern Italy.
AB  - Isolates of the rumen fluke Calicophoron daubneyi (Digenea: Paramphistomidae)
      from various hosts and three locations in southern Italy were characterized
      genetically. The second internal transcribed spacer (ITS-2) of ribosomal DNA
      (rDNA) plus flanking 5.8S and 28S sequence (ITS-2+) was amplified from individual
      rumen flukes by PCR. PCR-linked restriction fragment length polymorphism (PCR
      RFLP) analysis was performed using four different restriction endonucleases, and
      PCR products were sequenced. The PCR analyses from all the C. daubneyi specimens
      produced identical fragments, and the PCR-RFLP analyses did not show, with
      respect to any of the four restriction endonucleases, any differences between the
      C. daubneyi specimens. The sequence analyses of the ITS-2+ from each of the C.
      daubneyi specimens showed them all to be 428 bp, and composed of the entire ITS-2
      sequence (282 bp) plus the two partial flanking conserved sequences, 5.8S (99 bp)
      and 28S (47 bp). No intra-specific variation was observed in the nucleotide
      composition of the ITS-2+ (homology=100%). There was, however, an observable
      inter-specific variation between the ITS-2+ of C. daubneyi and the ITS-2+ of both
      Calicophoron calicophorum (homology=97.2 %) and Calicophoronmicrobothrioides
      (homology=97.4 %), both previously deposited in the GenBank. The finding of the
      present study shows that, as has already demonstrated for other parasitic
      helminths, ITS-2 can serve as an effective genetic marker for the molecular
      identification of paramphistomes, and as a useful tool for developing molecular
      epidemiological techniques for the study of C. daubneyi transmission patterns and
      prevalence in definitive and intermediate hosts.

PMID- 15961233
TI  - Bicelle membranes and their use for hydrophobic peptide studies by circular
      dichroism and solid state NMR.
AB  - Mixtures of dicaproyl- (DC), dimyristoyl- (DM) and 1-tetradecanoyl-2
      biphenylbutanoyl-(TBB) phosphatidylcholine (PC) in water produce bicelle
      membranes that are oriented by magnetic fields. DMPC/DCPC systems orient such
      that their membrane plane is parallel to the magnetic field, whereas for
      TBBPC/DCPC, the plane is perpendicular to the field. Partial temperature
      composition-hydration diagrams are established using solid-state 31P-NMR.
      DMPC/DCPC bicelles exist on a large range of composition but on a narrow
      temperature domain (25-45 degrees C). At converse, TBBPC/DCPC form bicelles on a
      narrow compositional range but over a large temperature span (10-70 degrees C).
      The TBBPC/DCPC bicelles are shown to be a very powerful potential tool to study
      the orientation of hydrophobic helices in membranes using wide line 15N-NMR. The
      DMPC/DCPC system that undergoes a micelle-to-bicelle transition on going from 10
      degrees C to 40 degrees C may be used with circular dichroism to study the state
      of association of hydrophobic helices within the membrane. Results suggest that
      the transmembrane fragment of the neu/erbB-2 receptor is monomeric in micellar
      medium and dimeric/multimeric in bicelle membranes.

PMID- 15961234
TI  - Postnatal development of intrinsic GABAergic rhythms in mouse hippocampus.
AB  - The local circuitry of the mammalian limbic cortices, including the hippocampus,
      is capable of generating spontaneous rhythmic activities of 0.5-4 Hz when
      isolated in vitro. These rhythmic activities are mediated by synchronous
      inhibitory postsynaptic potentials in pyramidal neurons as the result of repeated
      discharges of inhibitory interneurons. As such, they are thought to represent an
      intrinsic inhibitory rhythm. It is unknown at present whether such a rhythm
      occurs in the immature rodent hippocampus and, if so, the postnatal time window
      in which it develops. We explored these issues using our recently developed whole
      mouse hippocampal isolate preparation in vitro. We found that spontaneous
      rhythmic field potentials started to emerge in mouse hippocampal isolates around
      postnatal day 10, stabilized after postnatal day 15 and persisted into adulthood.
      In postnatal days 11-14 mouse hippocampi, the properties of these rhythmic
      potentials were in keeping with a CA3-driven, IPSP-based intrinsic network
      activity. The lack of spontaneous field rhythm in neonatal (postnatal days 2-7)
      hippocampi cannot be attributed to the excitatory activities mediated by gamma
      aminobutyric acid type A (GABA-A) receptors, as chloride-dependent
      hyperpolarizing inhibitory postsynaptic potentials were detectable in neonatal
      pyramidal neurons at voltages near resting potentials and pharmacological
      antagonisms of GABA-A receptors produced robust epileptiform discharges in
      neonatal hippocampi. High frequency afferent stimulation or applications of 4
      aminopyridine at low micromolar concentrations failed to induce persistent field
      rhythm in neonatal hippocampi, suggesting that an overall weak glutamatergic
      drive is not the sole causing factor. We suggest that the inhibitory postsynaptic
      potential-based spontaneous rhythmic field potentials develop in a discrete time
      window during the second postnatal week in the mouse hippocampus due to a fine
      tuning in the structure and function of CA3 recurrent circuitry and associated
      GABAergic inhibitory interneurons.

PMID- 15961235
TI  - Expression of somatostatin receptor subtypes (SSTR1-5) in Alzheimer's disease
      brain: an immunohistochemical analysis.
AB  - Somatostatin, widely distributed in human cortical brain regions, acts through
      specific high affinity somatostatin receptors (SSTR1-5) to exert profound effects
      on motor, sensory, behavioral, cognitive and autonomic functions. Somatostatin
      levels are consistently decreased in the cortex of Alzheimer's disease (AD) brain
      and in cerebrospinal fluid, and have become reproducible markers of this disease.
      In the present study, the distributional pattern of SSTR1-5 antigens in the
      frontal cortex of AD and age-matched control brains was studied using antipeptide
      polyclonal rabbit antibodies directed against the five human somatostatin
      receptor subtypes. All five SSTRs were differentially expressed as membrane and
      cytoplasmic proteins in cortical neurons with significant variations in control
      vs. AD brain. In AD cortical brain region, somatostatin and neuropeptide-Y
      positive neurons decreased (>70%), and glial fibrillary acidic protein-positive
      astrocytes significantly increased (>130%) in comparison to control brain. SSTR2
      and 4 were the predominant subtypes followed by SSTR1, 3 and 5. AD cortex showed
      a marked reduction in neuronal expression of SSTR4 and 5 and a modest decrease in
      SSTR2-like immunoreactivity without any changes in SSTR1 immunoreactive neurons.
      In contrast, SSTR3 was the only receptor subtype that increased in AD cortex. In
      AD cortex, SSTR1-, 3- and 4-like immunoreactivities were strongly expressed in
      glial cells but not SSTR2 and 5. These findings suggest the differential loss of
      immunoreactivity of SSTR2, 4 and 5 but not SSTR1, and increased SSTR3 in frontal
      cortex of AD brain as well as subtype-selective glial expression in AD brain. In
      summary, subtype-selective changes in the expression of SSTRs at protein levels
      in AD cortical regions suggest that somatostatin and SSTR-containing neurons are
      pathologically involved in AD and could possibly be used as markers of this
      disease.

PMID- 15961236
TI  - Vesicular glutamate transporter 1 immunostaining in the normal and epileptic
      human cerebral cortex.
AB  - Glutamate is the main excitatory neurotransmitter in the brain where, due to the
      activity of specific vesicular glutamate transporters, it accumulates in synaptic
      vesicles. The vesicular glutamate transporter 1 is found in the majority of axon
      terminals that form asymmetrical (excitatory) synapses in the rat neocortex.
      However, since there is no information available regarding the distribution of
      vesicular glutamate transporter 1 in the human neocortex, we have used
      correlative light and electron microscopy to define its expression in this
      tissue. We found that the distribution of vesicular glutamate transporter 1
      immunoreactivity is virtually identical to that found in the rat neocortex, both
      at the light and electron microscope levels. Therefore, we assessed whether
      vesicular glutamate transporter 1 immunostaining might be a useful tool to study
      the pathological alterations of glutamatergic transmission in the epileptic
      cerebral cortex. We analyzed the distribution of vesicular glutamate transporter
      1 in the peritumoral neocortex of patients with epilepsy secondary to low-grade
      tumors. In these regions, we found alterations in the pattern of vesicular
      glutamate transporter 1-immunoreactivity that perfectly matched the neuronal loss
      and gliosis, as well as the decrease in the number of asymmetrical synapses
      identified by electron microscopy in this tissue. Thus, vesicular glutamate
      transporter 1 immunostaining appears to be a reliable and simple tool to study
      glutamatergic synapses in the normal and epileptic human cerebral cortex.

PMID- 15961237
TI  - Further characterization of muscarinic agonist-induced epileptiform bursting
      activity in immature rat piriform cortex, in vitro.
AB  - The characteristics of muscarinic acetylcholine receptor agonist-induced
      epileptiform bursting seen in immature rat piriform cortex slices in vitro were
      further investigated using intracellular recording, with particular focus on its
      postnatal age-dependence (P+14-P+30), pharmacology, site(s) of origin and the
      likely contribution of the muscarinic acetylcholine receptor agonist-induced post
      stimulus slow afterdepolarization and gap junction functionality toward its
      generation. The muscarinic agonist, oxotremorine-M (10 microM), induced rhythmic
      bursting only in immature piriform cortex slices; however, paroxysmal
      depolarizing shift amplitude, burst duration and burst incidence were inversely
      related to postnatal age. No significant age-dependent changes in neuronal
      membrane properties or postsynaptic muscarinic responsiveness accounted for this
      decline. Burst incidence was higher when recorded in anterior and posterior
      regions of the immature piriform cortex. In adult and immature neurones,
      oxotremorine-M effects were abolished by M1-, but not M2-muscarinic acetylcholine
      receptor-selective antagonists. Rostrocaudal lesions, between piriform cortex
      layers I and II, or layer III and endopiriform nucleus in adult or immature
      slices did not influence oxotremorine-M effects; however, the slow
      afterdepolarization in adult (but not immature) lesioned slices was abolished.
      Gap junction blockers (carbenoxolone or octanol) disrupted muscarinic bursting
      and diminished the slow afterdepolarization in immature slices, suggesting that
      gap junction connectivity was important for bursting. Our data show that neural
      networks within layers II-III function as primary oscillatory circuits for burst
      initiation in immature rat piriform cortex during persistent muscarinic receptor
      activation. Furthermore, we propose that muscarinic slow afterdepolarization
      induction and gap junction communication could contribute towards the increased
      epileptiform susceptibility of this brain area.

PMID- 15961238
TI  - Immunohistological characterization of striatal and amygdalar structures in the
      telencephalon of the fire-bellied toad Bombina orientalis.
AB  - The subpallium of the fire-bellied toad Bombina orientalis was studied by means
      of enzyme-histological detection of NADPH-diaphorase and immunohistological
      demonstration of aspartate, GABA, calretinin, choline-acetyl transferase, Leu-and
      Met-enkephalin, neuropeptide Y, 5-hydroxy-tryptamine (serotonin), somatostatin,
      substance P and tyrosine-hydroxylase. As in other vertebrates, the striato
      pallidum is characterized by GABA-, substance P- and enkephalin-immunoreactivity.
      Neurons and fibers differing in immunoreactivity are arranged in layers. Choline
      acetyl transferase-immunoreactive neurons were found in a position corresponding
      to the mammalian cholinergic cell-group (Ch4-group), which therefore may be
      homologous to the nucleus basalis of Meynert. Within the amygdaloid complex, the
      cortical and lateral (vomeronasal) nuclei are similar in calretinin-, GABA-,
      NADPH-diaphorase-, enkephalin, substance P- and neuropeptide Y-(immuno)histology.
      The medial and central amygdaloid nuclei reveal a dense peptidergic innervation,
      and the medial amygdala additionally exhibits serotonergic fibers and cell bodies
      staining for neuropeptides and tyrosine-hydroxylase. Differences between Bombina
      and other anuran species exist, such as the absence of cholinergic neurons in the
      striatum. Our findings corroborate the view based on recent studies on the
      hodology and cytoarchitecture of the anuran telencephalon that the anuran ventral
      telencephalon contains most of the structures found in the mammalian brain. This
      concerns a septal region, a dorsal and ventral striato-pallidum including a
      nucleus accumbens and an amygdaloid complex consisting of a central, cortical and
      vomeronasal amygdala. The only major difference appears to concern the lack of a
      basolateral amygdala.

PMID- 15961240
TI  - Oxytocin-induced excitation of neurones in the rat central and medial amygdaloid
      nuclei.
AB  - Central oxytocin plays an important role in regulating emotionality. The amygdala
      expresses gonadal steroid-sensitive oxytocin binding sites in both the central
      and medial sub-nuclei, although the densities markedly differ between these
      nuclei. These studies examined the in vitro electrophysiological effects of
      oxytocin in the two amygdaloid nuclei and compared responses in female rats in
      different reproductive states (virgin, pregnant and lactating). Oxytocin (10(-9)
      10(-6)M) caused a concentration-dependent increase in the firing rate of 20-36%
      of the neurones in both nuclei. Although autoradiographic studies using the
      oxytocin receptor antagonist [(125)I]d(CH(2))(5)[Tyr(Me)(2),Thr(4),Orn(8),Tyr
      NH(2)(9)]-vasotocin showed a higher density of binding in the central nucleus of
      the amygdala than medial nucleus of the amygdala, neurones in the central nucleus
      of the amygdala had a much lower sensitivity to oxytocin: equivalent responses
      obtained with 10(-6)M in the central nucleus of the amygdala and 10(-8)M in the
      medial nucleus of the amygdala, and neurones in the central nucleus of the
      amygdala were insensitive to concentrations below 10(-6)M. Furthermore, repeated
      applications of oxytocin induced homologous desensitization in the central
      nucleus of the amygdala, but not medial nucleus of the amygdala-a single
      application of oxytocin producing long duration suppression of responses. This
      indicates that oxytocin has contrasting modes of action in the amygdala. Studies
      made across the reproductive cycle showed that lactating animals exhibited a
      larger proportion of oxytocin-responsive neurones in the medial nucleus of the
      amygdala and a smaller proportion in the central nucleus of the amygdala,
      compared with virgin or pregnant animals, indicating a peripartum shift in
      relative activation within the amygdala. However, changes in responses were not
      accompanied by changes in the density of oxytocin binding sites. These data show
      that oxytocin has a markedly different efficacy on neuronal activation in the
      central and medial sub-nuclei of the amygdala. The relative shift in excitatory
      responses between these two nuclei may underlie some of the neuroendocrine,
      behavioral and anxiolytic effects which have been ascribed to oxytocin in the
      periparturient rat.

PMID- 15961239
TI  - Biphasic actions of topiramate on monoamine exocytosis associated with both
      soluble N-ethylmaleimide-sensitive factor attachment protein receptors and Ca(2+)
      induced Ca(2+)-releasing systems.
AB  - To explore the pharmacological mechanisms of topiramate (TPM), we determined the
      effects of TPM on monoamine (dopamine and serotonin) exocytosis associated with N
      ethylmaleimide-sensitive factor attachment protein receptors and Ca(2+)-induced
      Ca(2+)-releasing systems, including inositol-triphosphate receptor and ryanodine
      receptor in freely moving rat pre-frontal cortex using in vivo microdialysis.
      During resting stage, Ca(2+) output from endoplasmic reticulum Ca(2+) store via
      inositol-triphosphate receptor regulates syntaxin-associated monoamine exocytosis
      mechanism, whereas during neuronal hyperexcitable stage, Ca(2+) output via
      ryanodine receptor regulates synaptobrevin-associated monoamine exocytosis
      mechanism. Basal monoamine releases were increased and decreased by
      therapeutically relevant and supratherapeutic concentration of TPM, respectively.
      The therapeutic-relevant concentration of TPM increased Ca(2+)-evoked release
      concentration-dependently; however, its stimulatory effect was attenuated in the
      supratherapeutic range. The K(+)-evoked releases were reduced by TPM
      concentration-dependently (from therapeutic to supratherapeutic ranges). The
      therapeutic-relevant concentration of TPM-induced elevation of basal release was
      reduced by cleavage with syntaxin and inhibition of inositol-triphosphate
      receptor predominantly, by cleavage with SNAP-25 and synaptobrevin weakly, but
      not by ryanodine receptor inhibitor. The therapeutic-relevant concentration of
      TPM-induced elevation of Ca(2+)-evoked release was reduced by cleavage with
      syntaxin and inositol-triphosphate receptor inhibitor selectively. The
      therapeutic-relevant concentration of TPM-induced reduction of K(+)-evoked
      monoamine release was abolished by cleavage with synaptobrevin, but was not
      affected by cleavage with SNAP-25 or synaptobrevin. The stimulatory effect of
      ryanodine receptor agonist on K(+)-evoked monoamine release was reduced by TPM,
      whereas that of inositol-triphosphate receptor agonist was not affected by TPM.
      Therefore, these results indicate that the combination of the effects of TPM on
      exocytosis mechanisms associated with SNARE and Ca(2+)-induced Ca(2+)-releasing
      systems, enhancement of inositol-triphosphate receptor/syntaxin and inhibition of
      ryanodine receptor/synaptobrevin in pre-frontal cortex, may be involved in
      clinical actions of TPM.

PMID- 15961241
TI  - Rapid damping of food-entrained circadian rhythm of clock gene expression in
      clock-defective peripheral tissues under fasting conditions.
AB  - Restricted feeding-induced free-running oscillation of clock genes in the liver
      was studied in homozygous Clock-mutant (Clock/Clock) mice. Similar to wild-type
      mice, Clock/Clock mice showed robust food-anticipatory behavioral activity in
      accordance with a restricted feeding schedule. Also, the peak of all clock gene
      mRNAs tested was phase-advanced in the liver of Clock/Clock mice as well as wild
      type mice, although the amplitude of clock gene expression was low in Clock/Clock
      mice. The food-anticipatory behavioral rhythm in Clock/Clock mice maintained a
      period similar to wild-type mice during 2-day fasting after the cessation of
      restricted feeding. However, during the fasting days after temporal feeding cues
      were removed, the oscillation of clock genes in the liver and heart, excluding
      the suprachiasmatic nuclei, appeared to result in arrhythmicity in Clock/Clock
      mice. Thus, although the CLOCK-based molecular mechanism is not required for the
      expression of food-anticipatory activity, intact CLOCK protein might be involved
      in sustaining several cycles of peripheral circadian oscillations after
      restricted feeding-induced resetting.

PMID- 15961242
TI  - Stimulation of acetylcholine receptor transcription by neuregulin-2 requires an N
      box response element and is regulated by alternative splicing.
AB  - The neuregulin (Nrg) family of growth/differentiation factors is encoded by at
      least four genes in the mammalian genome: nrg-1, nrg-2, nrg-3 and nrg-4. Nrg-1
      and Nrg-2 share the highest homology within the family, and the primary RNA
      transcripts from their encoding genes are subjected to extensive alternative
      splicing. Although little is known about the biological function of Nrg-2-4,
      their structural similarity with Nrg-1 suggests that they could account for some
      of the activities presently attributed to Nrg-1. Thus, at the neuromuscular
      junction Nrg-1 has been a favored candidate for the signal that activates
      selective acetylcholine receptor (AChR) transcription in synaptic myonuclei.
      However, we have recently shown that like Nrg-1, Nrg-2 can also activate AChR
      transcription in cultured myotubes and accumulates at the synaptic site. Synapse
      specific and Nrg-1-induced AChR transcription require an enhancer sequence, the N
      box, which is also mutated in some patients with congenital myasthenia gravis.
      Here, we show that Nrg-2-induced AChR transcription requires an N-box motif and
      is regulated by alternative splicing. We also show that unique Nrg-2 isoforms are
      differentially distributed between spinal cord and skeletal muscle, the tissues
      that harbor the cellular components of the neuromuscular synapse.

PMID- 15961243
TI  - Decreased adenosine receptor binding in dystonic brains of the dt(sz) mutant.
AB  - In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can
      be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit
      adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this
      movement disorder, adenosine A(1) receptor antagonists were previously found to
      worsen dystonia, while adenosine A(1) and A(2A) receptor agonists exerted
      pronounced beneficial effects. Therefore, in the present study, adenosine
      receptor A(1) and A(2A) binding was determined by autoradiographic analyses in
      dt(sz) hamsters under basal conditions, i.e. in the absence of a dystonic attack,
      and in a group of mutant hamsters which exhibited severe stress-induced dystonic
      attacks prior to kill. In comparison with non-dystonic control hamsters,
      [(3)H]DPCPX (8-cyclopentyl-1,3-dipropylxanthine) binding to adenosine A(1)
      receptors and [(3)H]CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N
      ethlycarboxamindoadenosine) binding to adenosine A(2A) receptors were
      significantly lower throughout the brain of dystonic animals. Under normal
      resting conditions, mutant hamsters showed significant decreases in adenosine
      A(1) (-12 to-42%) and in A(2A) (-19 to-34%) receptor binding compared with
      controls. Stressful stimulation increased adenosine A(1) and A(2A) receptor
      binding in almost all brain regions in both control and dystonic hamsters. The
      stress-induced increase was more marked in mutant hamsters, leading to a
      disappearance of differences in most regions compared with stimulated controls,
      except the striatum. In view of previous findings of striking beneficial effects
      of adenosine A(1) and A(2A) receptor agonists and of striatal dysfunctions in the
      dt(sz) mutant, the reduced adenosine receptor binding may be an important factor
      in the pathogenesis of paroxysmal dystonia.

PMID- 15961244
TI  - Post-exposure treatment attenuates noise-induced hearing loss.
AB  - Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are involved in
      sensory cell and neural death in the peripheral nervous system, including damage
      induced by noise trauma. Antioxidant administration prior to or concomitant with
      noise exposure can prevent auditory deficits, but the efficacy of a delayed
      treatment is not known. We have recently found continued reactive oxygen
      species/reactive nitrogen species formation in the ear for 7-10 days following
      noise exposure and reasoned that antioxidant intervention during this period
      should also reduce noise-induced hearing loss. Guinea-pigs were subjected to 4
      kHz octave band noise at 120 decibels sound- pressure-level (dB SPL) for 5 hours
      and received treatment with ROS and RNS scavengers (salicylate and trolox)
      beginning 3 days prior, 1 hour, 1, 3, or 5 days after noise exposure. Auditory
      thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and
      16 kHz, before and 10 days after noise exposure. Hair cell damage was analyzed by
      quantitative histology, and free radical activity was determined
      immunohistochemically via 4-hydroxynonenal and nitrotyrosine as markers of
      reactive oxygen species and reactive nitrogen species action. Delivered up to 3
      days after noise exposure, salicylate and trolox significantly reduced auditory
      brainstem response deficits, reduced hair cell damage, and decreased reactive
      oxygen species and reactive nitrogen species formation. Earlier drug treatment
      was more effective than later treatment. Our results detail a window of
      opportunity for rescue from noise trauma, and provide evidence for both
      morphological and functional protection by delayed pharmacological intervention.

PMID- 15961245
TI  - Effects of repeated maternal stress on FOS expression in the hypothalamic
      paraventricular nucleus of fetal rats.
AB  - The effects of repeated prenatal stress with different severity (restraint and
      immobilization) on Fos expression in the maternal and fetal hypothalamic
      paraventricular nucleus (PVN) were examined in rats. Acute stress treatment was
      performed for 30 min on gestational day 21, and repeated stress treatment for 30
      min daily for 5 days from gestational days 17-21. In the parvocellular region of
      the maternal PVN, the stress-induced increases in the number of Fos
      immunoreactive neurons were smaller in the repeated stress groups than the acute
      stress groups, indicating an adaptation of Fos expression to repeated stress. The
      attenuated Fos expression observed in the maternal PVN following repeated mild
      stress did not occur in the fetal PVN. In contrast, repeated immobilization
      stress caused a much smaller increase in Fos expression in the fetal PVN than did
      acute immobilization stress. The reduced Fos expression in the fetal PVN
      following repeated severe stress was thought to be due to cell death, since the
      fetal PVN in the chronic immobilization group revealed a reduction in the total
      number of cells and an increase in the number of apoptotic cells. In the female
      but not male fetuses, repeated restraint stress induced a significant increase in
      the number of apoptotic cells in the PVN. These findings suggest that the fetal
      PVN shows no adaptation of Fos expression to repeated maternal stress, but great
      vulnerability to cell death, including apoptosis. In addition, stress-induced
      apoptosis may more easily occur in the fetal PVN in females than males.

PMID- 15961246
TI  - Spike-dependent depolarizing afterpotentials contribute to endogenous bursting in
      gonadotropin releasing hormone neurons.
AB  - Pulsatile secretion of gonadotropin releasing hormone in mammals is thought to
      depend on repetitive and prolonged bursts of action potentials in specific
      neuroendocrine cells. We have previously described episodes of electrical
      activity in isolated gonadotropin releasing hormone neurons, but the intrinsic
      mechanisms underlying the generation of spike bursts are unknown. In acutely
      isolated gonadotropin releasing hormone neurons, which had been genetically
      targeted to express enhanced green fluorescent protein, current pulses generated
      spike-mediated depolarizing afterpotentials in 69% of cells. Spike-dependent
      depolarizing afterpotentials could evoke bursts of action potentials that lasted
      for tens of seconds. Brief pulses of glutamate (as short as 1 ms), which
      simulated excitatory postsynaptic potentials, also triggered spike-mediated
      depolarizing afterpotentials and episodic activity. These data indicate that
      spike-dependent depolarizing afterpotentials, an endogenous mechanism in
      gonadotropin releasing hormone neurons, likely contribute to the episodic firing
      thought to underlie pulsatile secretion of gonadotropin releasing hormone.
      Furthermore, fast excitatory postsynaptic potentials mediated by glutamate can
      activate this intrinsic mechanism.

PMID- 15961247
TI  - Postnatal neurogenesis in the medial cortex of the tropical lizard Tropidurus
      hispidus.
AB  - Young, adult and presumed old specimens of the tropical lizard Tropidurus
      hispidus, living in an almost steady warm habitat, have been the subjects of a 5
      bromodeoxiuridine immunocytochemical study to label proliferating brain cells.
      All animals showed abundant 5-bromodeoxiuridine-labeled nuclei in the ependyma of
      their telencephalic lateral ventricles, with these being especially abundant in
      the medial cortex ependyma. Surprisingly, adult animals displayed higher numbers
      of labeled nuclei when compared with those of young specimens. In a second
      experiment, in order to check the evolution of ependymal-labeled nuclei, adult
      specimens were allowed 4 h or 2, 4, 7, 15 or 30 days of survival after the 5
      bromodeoxiuridine pulse. Most labeled nuclei appeared isolated at short survival
      times (4 h and 2 days after the 5-bromodeoxiuridine pulse) but from day 4 and
      beyond, labeled nuclei appeared in couples or groups usually located in the
      ependyma. Labeled nuclei with vertical fusiform appearance in the inner plexiform
      layer or even recruited in the medial cortex cell layer were assumed to be
      migratory. These presumed migratory nuclei were unexpectedly few (less than 30%)
      when compared with other lizards, and they appeared much later; at 15 and 30 days
      after the pulse. This situation resembles that of mammals where only a small
      proportion of postnatally generated neurons can develop and survive.

PMID- 15961248
TI  - Glucocorticoid receptor involvement in pair bonding in female prairie voles: the
      effects of acute blockade and interactions with central dopamine reward systems.
AB  - Induction of partner preferences in monogamous prairie voles (Microtus
      ochrogaster) was used to examine the possibility that blockade of glucocorticoid
      receptors may be rewarding in females of this species. We first examined the
      ability of either a mineralocorticoid receptor antagonist (spironolactone) or a
      glucocorticoid receptor antagonist (RU-486) to induce partner preferences in
      females. Peripheral administration of either of the antagonists was capable of
      inducing partner preferences, although the effective dose for RU-486 was an order
      of magnitude lower than that for spironolactone. We then examined a potential
      interaction of glucocorticoid receptor with central dopamine in pair bonding by
      treating females with i.c.v. dopamine receptor antagonists (haloperidol,
      SCH23390, or eticlopride) prior to peripheral administration of RU-486. All of
      the dopamine antagonists were capable of reversing the effects of glucocorticoid
      receptor blockade on pair bonding. These results establish the ability for acute
      blockade of glucocorticoid to induce pair bonds in female voles. Further, this
      effect appears to be mediated via an interaction with central dopamine systems.
      Together these findings support the possibility that, unlike other model systems,
      reductions in glucocorticoid receptor activity may enhance reward in female
      prairie voles.

PMID- 15961249
TI  - Epileptogenic insult causes a shift in the form of long-term potentiation
      expression.
AB  - The relationship between epilepsy, modeled here by pentylenetetrazol kindling,
      and learning deficits, modeled here by long-term potentiation (LTP), was studied.
      The field excitatory postsynaptic potentials and population spikes (PS) were
      recorded from strata radiatum and pyramidale, respectively, in urethane
      anesthetized rat dorsal hippocampus CA1 area upon stimulation of Schaffer
      collaterals. To induce LTP, a 100 Hz primed-burst stimulation protocol was used.
      Experiments were carried out at approximately 30 days after the last
      pentylenetetrazol dose. The effects of voltage dependent calcium channel blocker
      verapamil and N-methyl-D-aspartate receptor antagonist MK-801 on LTP expression
      were examined. Tetanic stimulation elicited both field excitatory postsynaptic
      potential LTP and PS LTP in control animals, and LTP-induction of the PS in
      control animals was attenuated by MK-801, but not by verapamil. By contrast,
      kindled rats showed LTP of the PS only. MK-801 reduced the extent of potentiation
      of PS amplitude and verapamil inhibited the PS amplitude potentiation,
      completely. The results suggest that seizure induction modifies mechanisms
      underlying LTP induction and causes a shift in the form of LTP expression. The
      pentylenetetrazol-kindling-induced increase in PS LTP is sensitive to verapamil
      and not to MK-801 and therefore primarily dependent on activation of voltage
      dependent calcium channels rather N-methyl-D-aspartate receptors. Kindling may
      lead to a shift in synaptic plasticity thresholds much like the shift that occurs
      during aging, and such alterations may contribute to deficits in learning and
      memory.

PMID- 15961250
TI  - Depression and cortisol responses to psychological stress: a meta-analysis.
AB  - The purpose of this meta-analysis is to examine the association between
      depression and cortisol responses to psychological stressors. A total of seven
      studies comparing plasma or cortisol responses to psychological stressors in
      clinically depressed (MDD) and non-depressed (ND) individuals (N = 196: 98 MDD,
      98 ND; 83 men, 113 women; mean age = 40 years) were included. Sample size
      adjusted effect sizes (Cohen's d statistic) were calculated and averaged across
      baseline (before stressor onset), stress (stressor onset up to 25 min after
      stressor offset), and recovery (more than 25 min after stressor offset) periods.
      Overall, MDD and ND individuals exhibited similar baseline and stress cortisol
      levels, but MDD patients had much higher cortisol levels during the recovery
      period than their ND counterparts. There was also a significant time of day
      effect in which afternoon studies were more likely to reveal higher baseline
      cortisol levels, blunted stress reactivity, and impaired recovery in MDD
      patients. This blunted reactivity-impaired recovery pattern observed among the
      afternoon studies was most pronounced in studies with older and more severely
      depressed patients.

PMID- 15961251
TI  - Ecstasy and the concomitant use of pharmaceuticals.
AB  - Recent anecdotal evidence suggests that it is becoming increasingly popular among
      ecstasy users to attempt to negate certain side-effects or enhance the drug
      experience through the concomitant use of pharmaceutical drugs or supplements.
      This study was designed to explore the practice of deliberately using
      pharmaceuticals for any reason in association with ecstasy and related drug (ERD)
      use. A cross sectional survey was conducted with 216 adults who had used ecstasy
      at least once in the previous 6 months. Generally, this sample was young, well
      educated, and likely to be in some form of paid employment. Males were slightly
      overrepresented within the sample. About one quarter of the sample had
      deliberately taken a pharmaceutical substance for its putative effects on the
      euphoric effects of, or recovery from, ecstasy use. Those who reported using
      pharmaceuticals were significantly more likely to be male, had more 'apparent'
      years of use, and were more likely to have injected ERDs. As a result, there
      appears to be a need for harm reduction information for ecstasy users regarding
      the risks associated with the mixture of ERDs with pharmaceuticals and
      supplements. Particular attention should be paid to informing users of the
      potentially fatal serotonin syndrome that is likely to arise from combining
      serotonin-enhancing substances, such as ecstasy or SSRI and MAOI groups of
      antidepressants.

PMID- 15961252
TI  - Oestrogen-receptors (ER) are likely to be promiscuous: wider role for oestrogens
      and mimics.
AB  - The anti-breast cancer drug tamoxifen that binds to ER is metabolised in human
      liver by CYP2D6 isoenzyme, whilst the metabolism of 17beta-oestradiol (by
      hydroxylation) is by phase I biotransformation in the liver to 2
      hydroxyoestradiol and to 4-hydroxyoestradiol respectively by two isoenzymes of
      this mixed function oxidase CYP cytochromes P450 (EC 1.14.14.1); CYP1A2 and by
      CYP1B1. Nevertheless, it appears that the receptor (AhR) itself causes the
      expression of oestrogen-regulated target genes (studied by binding of dioxin).
      This is the result of an unknown signalling mechanism at the genome that is
      triggered directly by this receptor by binding promiscuously to ER (alpha or
      beta) sites. This has been observed even in the absence of oestrogens or mimics
      therefore in genome-binding investigations of target tissues such as uterus:
      oestrogen-receptor (ER) is likely to be promiscuous therefore. Furthermore, AhR
      (polycyclic aromatic hydrocarbon receptor), when activated by the binding of
      aromatic hydrocarbons (Ah) forms a complex with the aryl hydrocarbon nuclear
      translocator chaperone protein (Arnt). It is this binding to xenobiotic response
      elements in DNA that initiates expression of the appropriate oestrogen-regulated
      target-genes in the uterus and other target tissues (including mammary, ovaries,
      and brain). The likely promiscuity of oestrogen receptors is proposed to be the
      cause of numerous side effects when oestrogen is involved in therapy, these can
      be manifest in hormone replacement therapy (HRT) and in the incorporation of
      synthetic oestrogens in the wide varieties of oral contraceptives now available.

PMID- 15961254
TI  - Sustained repulsive magnetic force for bone lengthening.

PMID- 15961253
TI  - Insights from a novel tumor model: Indications for a quantitative link between
      tumor growth and invasion.
AB  - Both the lack of nutrient supply and rising mechanical stress exerted by the
      microenvironment appear to be able to cause discrepancies between the actual,
      observed tumor mass and that predicted by West et al.'s [A general model for
      ontogenetic growth. Nature 2001;413:628-31] universal growth model. Using our
      previously developed model we hypothesize here, that (1) solid tumor growth and
      cell invasion are linked, not only qualitatively but also quantitatively, that
      (2) the onset of invasion marks the time point when the tumor's cell density
      reaches a compaction maximum, and that (3) tumor cell invasion, reduction of
      mechanical confinement and angiogenesis can all contribute to an increase in the
      actual tumor mass m towards the level m(W) predicted by West et al.'s universal
      growth curve. These novel insights contribute to our understanding of
      tumorigenesis and thus may have important implications not only for experimental
      cancer research but also be of value for clinical purposes such as for
      predictions of tumor growth dynamics and treatment impact.

PMID- 15961255
TI  - A novel theory: biological processes mostly involve two types of mediators,
      namely general and specific mediators Endogenous small radicals such as
      superoxide and nitric oxide may play a role of general mediator in biological
      processes.
AB  - A great number of papers have shown that free radicals as well as bioactive
      molecules can play a role of mediator in a wide spectrum of biological processes,
      but the biological actions and chemical reactivity of the free radicals are quite
      different from that of the bioactive molecules, and that a wide variety of
      bioactive molecules can be easily modified by free radicals due to having
      functional groups sensitive to redox, and the significance of the interaction
      between the free radicals and the bioactive molecules in biological processes has
      been confirmed by the results of some in vitro and in vivo studies. Based on
      these evidence, this article presented a novel theory about the mediators of
      biological processes. The essentials of the theory are: (a) mediators of
      biological processes can be classified into general and specific mediators; the
      general mediators include two types of free radicals, namely superoxide and
      nitric oxide; the specific mediators include a wide variety of bioactive
      molecules, such as specific enzymes, transcription factors, cytokines and
      eicosanoids; (b) a general mediator can modify almost any class of the
      biomolecules, and thus play a role of mediator in nearly every biological process
      via diverse mechanisms; a specific mediator always acts selectively on certain
      classes of the biomolecules, and may play a role of mediator in different
      biological processes via a same mechanism; (c) biological processes are mostly
      controlled by networks of their mediators, so the free radicals can regulate the
      last consequence of a biological process by modifying some types of the bioactive
      molecules, or in cooperation with these bioactive molecules; the biological
      actions of superoxide and nitric oxide may be synergistic or antagonistic.
      According to this theory, keeping the integrity of these networks and the balance
      between the free radicals and the bioactive molecules as well as the balance
      between the free radicals and the free radical scavengers would be of vital
      importance for physiological processes, and disturbance of these networks and
      balances would be a critical factor of pathological processes. Therefore, the
      investigators who want to get a deep and full understanding of the mechanism of a
      biological process should pay attention to the roles of both free radical and
      bioactive molecule species, and the free radical scavengers, which are used for
      health protection, such a vitamin E and carotenoid, should be taken in a suitable
      dosage.

PMID- 15961256
TI  - [Molecular epidemiology of tuberculosis in Guadeloupe from 1994 to 2000].
AB  - In Guadeloupe, the incidence of tuberculosis decreased between 1994 and 2000. The
      rate of resistance to at least one antibiotic remained constant at 11%, whereas
      the rate of multiple-drug resistance increased from 0.9 to 2.4% in 2000. The
      proportion of patients of foreign origin (mainly from Haiti and the Dominican
      Republic) increased whereas the number of French patients decreased. These
      results show that the epidemiology of tuberculosis in Guadeloupe is similar to
      industrialized countries as older people, foreigners from countries where TB is
      endemic, and HIV+ patients are at a higher risk to declare tuberculosis disease.
      Molecular typing realized by spoligotyping showed the importance of previous
      successive colonizations and migrations as characterized by the presence of major
      phylogenetic families originating essentially from Northern Europe (Haarlem),
      Latin America and Mediterranean (LAM) and from Anglo-Saxon countries (X). The sub
      typing of clustered strains by IS6110-RFLP and by a PCR method based on the
      variable number of tandem DNA repeats (VNTR), highlighted 29 clusters,
      corresponding to 44.8% of clustered strains, and allowed to estimate the rate of
      recent transmission at 32.2%. The epidemiologic data associated with
      fingerprinting results underlined the importance of reactivation cases among
      older people, a significant number of imported TB cases without evident links,
      and casual contacts.

PMID- 15961257
TI  - Heroin overdose among young injection drug users in San Francisco.
AB  - OBJECTIVES: We sought to identify prevalence and predictors of heroin-related
      overdose among young injection drug users (IDU). METHODS: A total of 795 IDU
      under age of 30 years were interviewed in four neighbourhoods in San Francisco,
      California, USA. Participants were recruited as part of a broader study of HIV,
      hepatitis B and C among injecting drug users in San Francisco using street
      outreach and snowball techniques. Independent predictors of recent heroin
      overdose requiring intervention were determined using regression analysis.
      RESULTS: Of 795 injecting drug users under age of 30 years, 22% (174/795) of
      participants reported a heroin overdose in the last year. In stepwise multiple
      logistic regression, independent predictors of recent heroin overdose were
      lifetime incarceration exceeding 20 months (odds ratio (OR) = 2.99, 95%
      confidence interval (CI) = 1.52-5.88); heroin injection in the last 3 months (OR
      = 4.89, 95% CI = 2.03-11.74); cocaine injection in the last 3 months (OR = 1.67,
      95% CI = 1.14-2.45); injection of heroin mixed with methamphetamine in the last 3
      months (OR = 1.74, 95% CI = 1.15-2.65); ever tested for hepatitis B or C (OR =
      1.66 per year, CI = 1.09-2.54) and ever having witnessed another person overdose
      (OR = 2.89, 95% CI = 1.76-4.73). CONCLUSIONS: Individuals with high levels of
      incarceration are at great risk of overdose, and prison or jail should be
      considered a primary intervention site. Further research on the role of cocaine
      and amphetamine in heroin-related overdose is indicated.

PMID- 15961258
TI  - PCR-generated artefact from 16S rRNA gene-specific primers.
AB  - Artefacts consisting of concatenated oligonucleotide primer sequences were
      generated during sub-optimally performing polymerase chain reaction amplification
      of bacterial 16S rRNA genes using a commonly employed primer pair. These
      artefacts were observed during amplification for terminal restriction fragment
      length polymorphism analyses of complex microbial communities, and after
      amplification from DNA from a microbial culture. Similar repetitive motifs were
      found in gene sequences deposited in GenBank. The artefact can be avoided by
      using different primers for the amplification reaction.

PMID- 15961259
TI  - The rapid isolation and growth dynamics of the tsetse symbiont Sodalis
      glossinidius.
AB  - Sodalis glossinidius is known exclusively in endosymbiosis with tsetse flies
      (Genus: Glossina) and is one of the few insect bacterial symbionts that have been
      successfully cultured in vitro. This study details improved isolation and solid
      culture protocols that allow for a standardised and rapid preparation/maintenance
      of clonal material from individual flies. The isolation and culture of S.
      glossinidius was confirmed by partial sequencing of the 16S rDNA gene and
      specific PCR. In addition, the growth dynamics and changes in cell viability
      during liquid culture are described. The potential for culture of other
      endosymbiont taxa is discussed.

PMID- 15961260
TI  - Isolation of transposon mutants from Azospirillum brasilense Yu62 and
      characterization of genes involved in indole-3-acetic acid biosynthesis.
AB  - The molecular genetics of indole-3-acetic (IAA) synthesis and regulation in
      Azospirillum brasilense was investigated in this study. Tn5 mutagenesis was
      performed and five mutants with decreased IAA production were isolated. Five Tn5
      inserted genes from these mutants were cloned and sequenced. Four genes were
      reported for the first time to be involved in IAA production, namely, atrA, ftsA,
      omaA and aldA that code for GntR-family transcriptional regulator, iron-binding
      protein component of ABC-type Fe(3+) transport system, outer membrane protein,
      and aldehyde dehydrogenase, respectively. In addition, two genes atrB and atrC,
      with predicted proteins that showed high homology to aminotransferases, were
      cloned from the downstream of atrA in this bacterium. Studies also showed that
      complementation of atrA, ftsA and omaA were able to restore the IAA production of
      the corresponding IAA(-) mutants. Comparison of Fe(3+) concentrations in culture
      supernatants of the wild-type strain, the ftsA mutant and the complemented strain
      revealed that the iron-uptake ability of the ftsA mutant was highly reduced. This
      result also points to the necessity of iron as a metal ion in IAA synthesis.
      Statistical analysis showed no significant difference in the IAA accumulated in
      cells between the omaA mutant and the wild-type strain, suggesting the omaA might
      not affect IAA secretion but be involved in IAA production in other unknown ways.

PMID- 15961261
TI  - Cloning and expression of the reverse transcriptase component of pufferfish (Fugu
      rubripes) telomerase.
AB  - The enzyme telomerase is essential for maintaining the ends of linear
      chromosomes. It plays an important role in cell proliferation, differentiation,
      tumorigenesis and aging. Telomerase is composed of an RNA subunit (TR) and a
      reverse transcriptase catalytic subunit (TERT). We report here the cloning and
      characterization of the gene encoding the TERT subunit from a teleost fish, Fugu
      rubripes. This is the first fish TERT gene to be cloned. The fugu TERT (fTERT)
      gene comprises of 16 exons and 15 introns similar to the human TERT (hTERT), and
      encodes a 1074 amino acid protein. The fTERT protein showed 33% to 35% sequence
      identity to other vertebrate TERTs, and contained all the signature motifs of the
      TERT family. Analysis of the promoter region of fTERT showed the presence of
      several transcription factor binding sites (E2F-1, E-box, ER, Sp1 and USF sites)
      in common with the hTERT promoter, and whose binding factors are known to
      regulate hTERT. The fTERT gene is expressed in a variety of tissues, with high
      expression detected in the gill, testis, and ovary. fTERT expression was detected
      in an immortalized fugu eye-derived cell line. The level of expression was found
      to be higher in actively dividing cells and reduced at quiescence, suggesting
      cell cycle regulation of TERT and possibly telomerase activity, in this cell
      line.

PMID- 15961262
TI  - Epizootic cutaneous pythiosis in beef calves.
AB  - Enzootic bovine granulomatosis (EBG) is a disease that affects beef calves in the
      flooded Savanna regions of Venezuela. Although Pythium insidiosum was originally
      the suspected etiologic agent, nothing was done to demonstrate its presence in
      the infected animals. The objective of this study was to investigate the
      etiologic agent causing cutaneous lesions in a group of 63 calves diagnosed with
      EBG. The collected samples were analyzed by histopathology, immunohistochemistry,
      serology, and mycological techniques. The clinical manifestations of BEG included
      ulcerated and swollen granulomatous lesions on the limbs of young calves.
      Histopathological studies revealed an eosinophilic inflammatory reaction with
      neutrophils, giant cells and branching hyphae with the Splendore-Hoeppli
      phenomenon. Immunofluorescence analysis identified the branching hyphae as
      elements of the fungal-like organism P. insidiosum. Wet mounts in 10% KOH
      revealed hyaline slender branching hyaline coenocytic hyphae, but cultures from
      those samples were negative. Anti-P. insidiosum immunoglobulins were also
      demonstrated in the collected sera of the affected bovines using latex
      agglutination, immunodiffusion, ELISA, and Western Blot. The histopathological,
      immunohistochemical, and serological tests showed for the first time that P.
      insidiosum could be involved in epizootic bovine pythiosis.

PMID- 15961263
TI  - The effect of endogenous formaldehyde on the rat aorta endothelial cells.
AB  - Previous studies have demonstrated endogenous formaldehyde (FA) may be involved
      in endothelial damage, and may be a potential factor of vulnerability of
      atherosclerosis. However, the mechanism has not been characterized. The present
      studies examined DNA-protein cross-links (DPC) formation in rat aorta endothelial
      cells (RAECs) treated with formaldehyde, hydrogen peroxide (H2O2), or
      formaldehyde with equal molar concentration of H2O2, which is produced with
      formaldehyde in the body at the same time. Using a K+/SDS precipitation assay for
      DPC determination, concentration-dependent increases in DPC formation were
      observed 1.5 h after treatment of RAECs with 0.01-2mM FA, H2O2, or FA with equal
      molar concentration of H2O2. Time-dependent increases in DPC formation were also
      observed at 0.5-4 h time point after treatment of RAECs with 0.05 and 0.1mM FA,
      or 0.1mM FA with H2O2. The DPC levels reduced after treatment with FA and equal
      molar concentration of H2O2, compared with treatment with FA alone. FA may be
      less cytotoxic, as FA alone did not affect the cell viability even treating for
      4h, until the treatment concentration reached 2mM. However, H2O2, and FA with
      H2O2 induced significant decreases of cell viability. These studies suggest that
      FA and H2O2 may injure endothelial cells synergistically, and low concentration
      of FA (0.05-0.1) may contribute to the endothelial injury in the body during
      aging.

PMID- 15961264
TI  - Inhibition of alpha7-nicotinic acetylcholine receptor expression by arsenite in
      the vascular endothelial cells.
AB  - The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR), expressed in the
      neuronal and non-neuronal cells, has been shown to regulate cell proliferation.
      However, the expression and function of the alpha7-nAChR in the proliferation of
      the vascular endothelial cells remain unclear. In this study, we investigated the
      expression of the alpha7-nAChR in the arsenite-exposed vascular endothelial
      cells. The vascular endothelial cells SVEC4-10 and porcine aorta endothelial
      cells (PAEC) expressed the alpha7-nAChR proteins. Moreover, the location of the
      alpha7-nAChR proteins on cell membrane of the vascular endothelial cells was
      identified by the alpha7-nAChR binding to a tetramethylrhodamine-labeled alpha
      bungarotoxin (alpha-BTX). Arsenite (20 microM, 24 h) significantly induced the
      cytotoxicity, cell growth inhibition, and apoptosis in the vascular endothelial
      cells. The level of alpha7-nAChR proteins was concentration dependently decreased
      in the arsenite-treated endothelial cells. Furthermore, a specific alpha7-nAChR
      antagonist, alpha-BTX, inhibited the cell viability in the vascular endothelial
      cells. Nevertheless, alpha-BTX, and a alpha7-nAChR agonist, nicotine, did not
      significantly alter the cytotoxicity in the arsenite-treated endothelial cells.
      In addition, arsenite decreased the level of endothelial nitric oxide synthase
      proteins but did not alter choline acetyltransferase proteins in the SVEC4-10
      endothelial cells. Together, our results indicate that arsenite can inhibit the
      alpha7-nAChR protein expression and cause the cell injury in the vascular
      endothelial cells.

PMID- 15961265
TI  - Comparison between the characteristics of follicular fluid and the developmental
      competence of bovine oocytes.
AB  - There are great differences in the developmental competence of oocytes collected
      from individual cows. Oocytes grow and mature in the follicular fluid (FF). In
      the present study, characteristics of the FF of each ovary and the developmental
      competence of enclosed oocytes were investigated, and these data were then
      compared. A total of 37 pairs of ovaries were collected from beef heifers. The
      concentration of magnesium (Mg), aspirate aminotransferase (AST), nonesterified
      fatty acids (NEFA), and lactate dehydrogenase (LDH) in the FF were great compared
      with serum standard. Several significant correlations among these characteristics
      were detected. Forty-eight hours after fertilization, the stage of embryo
      development at an advanced developmental stage (>6 cell stage) is related to the
      rate of blastulation 8 days after fertilization. In addition, a significantly
      positive or negative correlation was observed between the developmental
      competence (the rate of cleavage in the embryo and blastulation) and the
      concentration of the icterus index (ICT) or blood urea nitrogen (BUN) in the FF.
      In conclusion, the quality of oocytes is affected by the environment in the
      follicle, and BUN or ICT is a predictable index of the developmental competence
      of oocytes.

PMID- 15961266
TI  - Particle size and surface charge affect particle uptake by human dendritic cells
      in an in vitro model.
AB  - Current vaccine development includes optimization of antigen delivery to antigen
      presenting cells, such as dendritic cells (DC). Particulate systems have
      attracted increasing attention in the development of vaccine delivery systems. In
      the present study, we investigated DC uptake of model fluorescent polystyrene
      particles with a broad size range and variable surface properties. Localization
      of particles was investigated using confocal laser scanning microscopy and uptake
      was quantified by flow cytometry. Immature DC were generated from mononuclear
      cells isolated from human blood. The polystyrene particles interacted with the DC
      throughout the tested diameter range of 0.04-15 microm in a time- and
      concentration-dependent manner. The optimal particle diameter for fast and
      efficient acquisition by a substantial percentage of the DC was 0.5 microm and
      below. The surface of 1 and 0.1 microm polystyrene particles was covalently
      modified with different polyaminoacids/proteins, yielding particles with varying
      surface charge. Uptake of 1 microm particles was greatly enhanced when particles
      displayed a positive surface charge. In general, the present findings establish
      that particle diameters of 0.5 microm and below were optimal for DC uptake;
      however uptake of larger particles could be greatly enhanced by rendering the
      particle surface positive. Whether increased particle uptake is correlated with
      increased immune responses, remains to be established.

PMID- 15961267
TI  - Efficacy of stent angioplasty for symptomatic stenoses of the proximal vertebral
      artery.
AB  - BACKGROUND: To evaluate the safety and efficacy of stent angioplasty in the
      treatment of symptomatic arteriosclerotic stenoses of the proximal vertebral
      artery (VA). METHODS: Thirty-eight symptomatic stenoses of the vertebral origin
      were treated with flexible balloon-expandable coronary stents. Angiographic and
      clinical follow-up examinations were obtained in 26 patients at a mean of 11
      months. RESULTS: The immediate post-procedural angiographic results showed no
      residual stenosis in 33 vessels and mild residual stenoses in five vessels.
      Periprocedurally, there were two asymptomatic technical complications and one
      TIA. During follow-up re-stenosis could be detected in 10 cases (36%), and vessel
      occlusions in two patients. Two stents were broken. One of the restenosis caused
      a TIA within the follow-up period. CONCLUSIONS: Flexible balloon-expandable
      coronary stents proved to be save and effective in preventing vertebrobasilar
      stroke but were incapable to preserve the proximal vertebral artery lumen. For
      the VA origine an adequate stent, self-expanding, bioresorbable, or drug-eluting
      has to be found.

PMID- 15961268
TI  - A biomechanical study on flexible intramedullary nails used to treat pediatric
      femoral fractures.
AB  - Flexible intramedullary nails have been indicated to treat femoral fractures in
      pediatric patients. The purpose of this study was to examine the stability of
      simulated transverse fractures after retrograde intramedullary flexible nail
      fixation. Various nail diameter combinations were tested using composite femurs
      in bending, torsion, and a combined axial/bending test where a vertical
      compressive force was applied to the femoral head. The cross-sectional percent
      area fill of the nails within the femurs was also determined. In 4 point bending,
      the greatest repair stiffness was 12% of the intact stiffness. In torsion, the
      greatest stiffness was 1% of the intact stiffness for either internal or external
      rotation. The greatest repair stiffness was 80% of the intact stiffness for a
      compressive load applied to the femoral head. Nail combinations with single nail
      diameters greater than 40% of the mid-shaft canal width, as measured from an AP
      radiograph, prevented the fracture from being reduced and left a posterior gap.
      Flexible intramedullary nails may be of value in the treatment of pediatric
      femoral fractures, but care must be taken to insert nails that are correctly
      sized for the canal and to protect the healing fracture from high torsional and
      bending loads.

PMID- 15961269
TI  - To what extent do variabilities in hormones, metabolites and energy intake
      explain variability in milk yield?
AB  - The objective of the present paper is to describe the extent to which variability
      in milk yield can be explained by variability in plasma hormones, metabolites and
      DE intake. Results from a study including 317 cows and 634 lactations were used.
      Detailed registration of performance was carried out on these cows and 10,809
      plasma samples analyzed for selected hormones and metabolites. Univariate
      analysis was carried out on energy-corrected milk yield and concentrations of
      selected plasma hormones (insulin, growth hormone (GH) and triiodothyronine
      (T3)), metabolites (non-esterified fatty acids (NEFA)), glucose, beta
      hydroxybutyrate (BOHB) and urea nitrogen (BUN), and digestible energy intake (DE
      intake) to estimate between-cow variation through lactations. Partial least
      square (PLS) models were subsequently run to estimate the extent to which between
      cow differences in energy-corrected milk yield could be explained by between-cow
      differences in hormone concentrations, metabolite concentration or DE intake. The
      between-cow variability in energy-corrected milk yield and the hormones and
      metabolites were generally found to be considerable and total variance changed
      through lactation, particularly for GH, T3, NEFA and BOHB. In this study, the
      total variance was highest in third lactation cows. When analyzed separately
      using partial least square models, hormones, metabolites and DE intake accounted
      for 24, 25 and 26% of the variability in ECM, respectively. Insulin and glucose
      were the single most important predictors among the selected hormones and
      metabolites. When including both the hormones and metabolites, the model
      explained 36% of the between-cow variability in ECM and this figure was increased
      to 53% if DE intake was also included. The lack of additivity in the variability
      explained shows that hormones, metabolites and DE intake were correlated
      illustrating the integration and orchestration of metabolism and intake.
      Perspectives of the analysis for use in prevention of diseases and reproduction
      are briefly discussed.

PMID- 15961270
TI  - [Severe subarachnoid haemorrhage].

PMID- 15961271
TI  - Cognitive impairment in three subtypes of multiple sclerosis.
AB  - Patients with relapsing, primary progressive, and secondary progressive MS were
      administered the Tower of London and the Stroop Color-Word Interference Test,
      yielding several measures of executive function and speeded information
      processing. MS patients' performance was compared with healthy controls and with
      a clinical control group consisting of patients with rheumatoid arthritis. The MS
      patients performed the tests more slowly, but did not differ from either group of
      controls on measures of executive function. Slowing in the speed of information
      processing was characteristic of MS patients across two basic tasks differing in
      terms of controlled versus automatic processing and in terms of whether or not
      rapid responding was an explicit feature of successful performance. Although
      evident in all subtypes, this slowing was more pronounced in secondary
      progressive patients and somewhat less pronounced in primary progressive
      patients. Furthermore, the slowing was unrelated to patients' disability status
      or level of depression.

PMID- 15961273
TI  - Beyond emotion archetypes: databases for emotion modelling using neural networks.
AB  - There has been rapid development in conceptions of the kind of database that is
      needed for emotion research. Familiar archetypes are still influential, but the
      state of the art has moved beyond them. There is concern to capture emotion as it
      occurs in action and interaction ('pervasive emotion') as well as in short
      episodes dominated by emotion, and therefore in a range of contexts, which shape
      the way it is expressed. Context links to modality-different contexts favour
      different modalities. The strategy of using acted data is not suited to those
      aims, and has been supplemented by work on both fully natural emotion and emotion
      induced by various technique that allow more controlled records. Applications for
      that kind of work go far beyond the 'trouble shooting' that has been the focus
      for application: 'really natural language processing' is a key goal. The
      descriptions included in such a database ideally cover quality, emotional
      content, emotion-related signals and signs, and context. Several schemes are
      emerging as candidates for describing pervasive emotion. The major contemporary
      databases are listed, emphasising those which are naturalistic or induced,
      multimodal, and influential.

PMID- 15961272
TI  - High-density single-nucleotide polymorphism maps of the human genome.
AB  - Here we report a large, extensively characterized set of single-nucleotide
      polymorphisms (SNPs) covering the human genome. We determined the allele
      frequencies of 55,018 SNPs in African Americans, Asians (Japanese-Chinese), and
      European Americans as part of The SNP Consortium's Allele Frequency Project. A
      subset of 8333 SNPs was also characterized in Koreans. Because these SNPs were
      ascertained in the same way, the data set is particularly useful for modeling.
      Our results document that much genetic variation is shared among populations. For
      autosomes, some 44% of these SNPs have a minor allele frequency > or =10% in each
      population, and the average allele frequency differences between populations with
      different continental origins are less than 19%. However, the several percentage
      point allele frequency differences among the closely related Korean, Japanese,
      and Chinese populations suggest caution in using mixtures of well-established
      populations for case-control genetic studies of complex traits. We estimate that
      approximately 7% of these SNPs are private SNPs with minor allele frequencies
      <1%. A useful set of characterized SNPs with large allele frequency differences
      between populations (>60%) can be used for admixture studies. High-density maps
      of high-quality, characterized SNPs produced by this project are freely
      available.

PMID- 15961274
TI  - As2O3-induced c-Src/EGFR/ERK signaling is via Sp1 binding sites to stimulate
      p21WAF1/CIP1 expression in human epidermoid carcinoma A431 cells.
AB  - Arsenic has been effectively used to treat acute promyelocytic leukemia, and can
      induce cell cycle arrest or apoptosis in human solid tumors. Previously, we have
      demonstrated that As2O3 can induce p21WAF1/CIP1 (p21) expression in A431 cells
      and then due to cellular cytotoxicity. Presently, we have clarified these
      signaling events and compared them with EGF. Using reporter assay, RT-PCR and
      Western blotting, we show that c-Src activation might be a prerequisite for As2O3
      induced EGFR/Ras/Raf/ERK signaling. Furthermore, with the aids of 5'-deletion and
      site-directed mutagenesis, we demonstrate that Sp1 binding sites, ranging from 
      64 to -84 bp, are essential for As2O3- or EGF-regulated p21 expression. Finally,
      our experiments utilizing cycloheximide prompt the suggestion that the stability
      of mRNA or protein also contributes to As2O3- or EGF-induced p21 expression.
      Taken together, we conclude that the Sp1 binding sites are required for As2O3
      induced p21 gene transcription through c-Src/EGFR/Ras/Raf/ERK pathway.
      Furthermore, post-transcriptional or post-translational stabilization mechanism
      is also essential for As2O3-induced p21 expression. EGF-induced p21 expression
      may involve similar mechanisms as those that operate in the As2O3-mediated
      reactions in A431 cells.

PMID- 15961275
TI  - Transcriptional regulation of plasminogen activator inhibitor-1 by transforming
      growth factor-beta, activin A and microphthalmia-associated transcription factor.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is a key molecule that regulates
      turnover of the extracellular matrix. In the present study, we characterized PAI
      1 gene expression in mast cells and melanocytes. In bone marrow-derived cultured
      mast cells, up-regulation of the PAI-1 gene was observed upon treatment with TGF
      beta1, and was regulated at the transcriptional level. Microphthalmia-associated
      transcription factor (MITF), a member of the basic helix-loop-helix leucine
      zipper family of tissue-specific transcription factors predominantly expressed in
      mast cells, melanocytes and osteoclasts, also stimulated PAI-1 gene
      transcription, and TGF-beta1 did not increase PAI-1 mRNA levels in mast cells
      from mi/mi mice expressing dominant-negative MITF. MITF isoforms regulated TGF
      beta1-induced transcription of PAI-1 differently; MITF-E-mediated transcription
      was further increased by TGF-beta1, whereas transcriptional activation by TGF
      beta1 was blocked by MITF-M or MITF-mc expression. In contrast, activin A,
      another member of the TGF-beta family, enhanced transcription induced by MITF-M,
      as well as by MITF-E, although MITF-mc blocked activin A-induced transcription of
      PAI-1. Different regulation of PAI-1 gene expression upon TGF-beta1 and activin A
      treatment was also detected in B16 melanocytes; TGF-beta1 transiently increased
      the PAI-1 mRNA level, whereas activin A had prolonged effects on up-regulation of
      PAI-1. Our results on the control of PAI-1 gene expression by MITF isoforms, TGF
      beta1 and activin A suggest that discrete regulation of the plasminogen activator
      system occurs in a cell type-specific manner.

PMID- 15961276
TI  - Role of PDE3B in insulin-induced glucose uptake, GLUT-4 translocation and
      lipogenesis in primary rat adipocytes.
AB  - In adipocytes, phosphorylation and activation of PDE3B is a key event in the
      antilipolytic action of insulin. The role of PDE4, another PDE present in
      adipocytes, is not yet known. In this work we investigate the role of PDE3B and
      PDE4 in insulin-induced glucose uptake, GLUT-4 translocation and lipogenesis.
      Inhibition of PDE3 (OPC3911, milrinone) but not PDE4 (RO 20-1724) lowered insulin
      induced glucose uptake and lipogenesis, especially in the presence of
      isoproterenol (a general beta-adrenergic agonist), CL316243, a selective beta3
      adrenergic agonist, and pituitary adenylate cyclase-activating peptide. The
      inhibitory effect of OPC3911 was associated with reduced translocation of GLUT-4
      from the cytosol to the plasma membrane. Both OPC3911 and RO 20-1724 increased
      protein kinase A (PKA) activity and lipolysis. H89, a PKA inhibitor, did not
      affect OPC3911-mediated inhibition of insulin-induced glucose uptake and
      lipogenesis, whereas 8-pCPT-2'-O-Me-cAMP, an Epac agonist which mediates PKA
      independent cAMP signaling events, mimicked all the effects of OPC3911. Insulin
      mediated activation of protein kinase B, a kinase involved in insulin-induced
      glucose uptake, was apparently not altered by OPC3911. In summary, our data
      suggest that PDE3B, but not PDE4, contributes to the regulation of insulin
      induced glucose uptake, GLUT-4 translocation, and lipogenesis presumably by
      regulation of a cAMP/Epac signalling mechanisms.

PMID- 15961277
TI  - Cell-surface targeting of alpha2-adrenergic receptors -- inhibition by a
      transport deficient mutant through dimerization.
AB  - We previously demonstrated that the alpha2B-adrenergic receptor mutant, in which
      the F(x)6IL motif in the membrane-proximal carboxyl terminus were mutated to
      alanines (alpha2B-ARm), is deficient in export from the endoplasmic reticulum
      (ER). In this report, we determined if alpha2B-ARm could modulate transport from
      the ER to the cell surface and signaling of its wild-type counterpart. Transient
      expression of alpha2B-ARm in HEK293T cells markedly inhibited cell-surface
      expression of wild-type alpha2B-AR, as measured by radioligand binding.
      Subcellular localization demonstrated that alpha2B-ARm trapped alpha2B-AR in the
      ER. The alpha2B-AR was shown to form homodimers and heterodimers with alpha2B-ARm
      as measured by co-immunoprecipitation of the receptors tagged with green
      fluorescent protein and hemagglutinin epitopes. In addition to alpha2B-AR, the
      transport of alpha2A-AR and alpha2C-AR to the cell surface was also inhibited by
      alpha2B-ARm. Furthermore, transient expression of alpha2B-ARm significantly
      reduced cell-surface expression of endogenous alpha2-AR in NG108-15 and HT29
      cells. Consistent with its effect on alpha2-AR cell-surface expression, alpha2B
      ARm attenuated alpha2A-AR- and alpha2B-AR-mediated ERK1/2 activation. These data
      demonstrated that the ER-retained mutant alpha2B-ARm conferred a dominant
      negative effect on the cell-surface expression of wild-type alpha2-AR, which is
      likely mediated through heterodimerization. These data indicate a crucial role of
      ER export in the regulation of cell-surface targeting and signaling of G protein
      coupled receptors.

PMID- 15961278
TI  - A long-term follow-up study of radiographically evident degenerative changes in
      the temporomandibular joint with different conditions of disk displacement.
AB  - The purpose of this retrospective study is to assess the relationship between an
      initial and persisting condition of disk displacement (DD) and the long-term
      course of radiographically evident degenerative changes of the temporomandibular
      joint (TMJ). Nineteen patients agreed to a radiographic follow-up examination of
      29 joints and were included in this study. The joints were radiographically
      assessed at the first visit and at least 46 months after the first visit (mean
      89.3 months). At the time of the follow-up, all subjects had a good clinical
      course after a favorable response to the treatments. There were significant
      relationships between the initial diagnosis of DD and the interval change in the
      morphology of the articular eminence. The articular eminence became flattened or
      deformed only in the joints with persistent DD without reduction. And there was a
      tendency that the condyle became smaller in the joints initially with permanent
      DD and in the joints which show a progression in the disk-condylar relationship.
      The results of this study suggested that, in the joints with persisting non
      reducing disk displacement, flattening and deformation of the articular eminence
      and regression of the condylar size were likely to happen even after symptoms and
      signs of TMJ disorders were resolved or reduced.

PMID- 15961279
TI  - Surgically assisted rapid maxillary expansion (SARME): a review of the
      literature.
AB  - Transverse maxillary hypoplasia, in adolescents and adults, is frequently seen in
      non-syndromal and syndromal patients including cleft patients. In skeletally
      matured patients, the uni- or bilateral transverse hypoplasia can be corrected by
      means of a surgically assisted rapid maxillary expansion. The treatment is a
      combination of orthodontics and surgical procedures and provides dental arch
      space for alignment of teeth. The procedure also causes a substantial enlargement
      of the maxillary apical base and of the palatal vault, providing space for the
      tongue for correct swallowing and thus preventing relapse. In addition, a
      distinct subjective improvement in nasal breathing associated with enlargement of
      the nasal valve towards normal values is seen with an increase of nasal volume in
      all compartments. In this article we give a review on surgically assisted rapid
      maxillary expansion. We conclude that there is no consensus in the searched
      literature regarding either the surgical technique, the type of distractor used
      (tooth-borne or bone-borne), the existence, cause and amount of relapse and
      whether or not overcorrection is necessary. A proposal for a prospective
      randomized patient study in order to find answers to the lacunas in knowledge
      regarding this treatment is done.

PMID- 15961280
TI  - Relationship between the pharyngeal airway space and craniofacial morphology,
      taking into account head posture.
AB  - This study assessed the relationship between craniofacial characteristics and the
      size of the pharyngeal airway space (PAS), taking into account head posture.
      Sixty dental students 25-30 years of age (30 men and 30 women) were examined by
      lateral cephalometry. The data were corrected with the use of appropriate
      regression equations for the PAS. The PAS significantly correlated with hyoid
      position, maxillary and mandibular size, maxillary and mandibular prognathism,
      and mandibular inclination. A large, anteriorly positioned mandible was
      associated with a large PAS-TP (the most proximal distance between the posterior
      pharyngeal wall and the tongue base). Uvula length and PNS-Ba (the distance
      between the most posterior point of the hard palate and the most inferior point
      of the anterior foramen magnum) correlated with PAS-UP (the most proximal
      distance between the posterior pharyngeal wall and uvula). Our results suggest
      that the anteroposterior dimension of the PAS is substantially affected by the
      size of the enclosure surrounding the PAS, including the maxilla, mandible and
      soft palate.

PMID- 15961281
TI  - Single staged, z-plasty supported, wedge excision modification for treatment of
      auricular lesions under local anesthesia: a technical note.
AB  - Following wedge-excision of auricular lesions, a triangular-cartilage only
      excision is planned at the tip of the wedge. The dimensions and the angles of
      this cartilage can be modified as much as the required helical rotation. After
      approximating the cartilage edges a notching deformity may be observed which can
      be improved using single or multiple z-plasties.

PMID- 15961282
TI  - Unusual penetrating orbit injury.
AB  - Penetrating head and face injuries can cause hemorrhages, neurological lesions,
      visual acuity loss, fractures and facial deformities. This report discusses an
      injury caused by a knife that penetrated the left orbit and reached the skull
      base without damaging any important structures. The knife was removed through the
      entrance wound and no complications were observed either during or after surgery.

PMID- 15961283
TI  - The ketogenic diet influences the levels of excitatory and inhibitory amino acids
      in the CSF in children with refractory epilepsy.
AB  - The ketogenic diet (KD) is an established treatment for medically refractory
      pediatric epilepsy. Its anticonvulsant mechanism is still unclear. We examined
      the influence of the KD on the CSF levels of excitatory and inhibitory amino
      acids in 26 children (mean age 6.1 years) with refractory epilepsy. Seventeen
      amino acids were determined before and at a mean of 4 months after the start of
      the KD. Seizures were quantified. Highly significant changes were found in eight
      amino acids: increases in GABA, taurine, serine, and glycine and decreases in
      asparagine, alanine, tyrosine and phenylalanine. However, aspartate, glutamate,
      arginine, threonine, citrulline, leucine, isoleucine and valine/methionine
      remained unchanged. A significant correlation with seizure response was found for
      threonine (P=0.016). The GABA levels were higher in responders (>50% seizure
      reduction) than in nonresponders during the diet (P=0.041). In the very good
      responders (>90% seizure reduction), the GABA levels were significantly higher at
      baseline as well as during the diet. Age differences were found with
      significantly larger decreases in glutamate and increases in GABA in connection
      with the diet in younger children. Our results indicate that the KD significantly
      alters the levels of several CSF amino acids that may be involved in its
      mechanism of action and the increase in GABA is of particular interest.

PMID- 15961284
TI  - Performance of a seizure warning algorithm based on the dynamics of intracranial
      EEG.
AB  - During the past decade, several studies have demonstrated experimental evidence
      that temporal lobe seizures are preceded by changes in dynamical properties (both
      spatial and temporal) of electroencephalograph (EEG) signals. In this study, we
      evaluate a method, based on chaos theory and global optimization techniques, for
      detecting pre-seizure states by monitoring the spatio-temporal changes in the
      dynamics of the EEG signal. The method employs the estimation of the short-term
      maximum Lyapunov exponent (STL(max)), a measure of the order (chaoticity) of a
      dynamical system, to quantify the EEG dynamics per electrode site. A global
      optimization technique is also employed to identify critical electrode sites that
      are involved in the seizure development. An important practical result of this
      study was the development of an automated seizure warning system (ASWS). The
      algorithm was tested in continuous, long-term EEG recordings, 3-14 days in
      duration, obtained from 10 patients with refractory temporal lobe epilepsy. In
      this analysis, for each patient, the EEG recordings were divided into training
      and testing datasets. We used the first portion of the data that contained half
      of the seizures to train the algorithm, where the algorithm achieved a
      sensitivity of 76.12% with an overall false prediction rate of 0.17h(-1). With
      the optimal parameter setting obtained from the training phase, the prediction
      performance of the algorithm during the testing phase achieved a sensitivity of
      68.75% with an overall false prediction rate of 0.15h(-1). The results of this
      study confirm our previous observations from a smaller number of patients: the
      development of automated seizure warning devices for diagnostic and therapeutic
      purposes is feasible and practically useful.

PMID- 15961285
TI  - Social behaviors in persons with and without persecutory delusions.

PMID- 15961286
TI  - Mutation in the vesicular monoamine gene, SLC18A1, associated with schizophrenia.

PMID- 15961288
TI  - Detection of vanB genotype enterococci in Iran.

PMID- 15961287
TI  - Increased nicotine and cotinine levels in smokers with schizophrenia and
      schizoaffective disorder is not a metabolic effect.
AB  - It has been hypothesized that smokers with schizophrenia take in more nicotine
      per cigarette than smokers without this disorder. This study examines this
      phenomenon by comparing the serum nicotine and cotinine levels in smokers with
      either schizophrenia or schizoaffective disorder compared to control smokers
      without mental illness. Serum cotinine and nicotine levels of smokers with
      schizophrenia or schizoaffective disorder were 1.3 times higher than control
      smokers (cotinine 291 versus 227 ng/mL; p = 0.0115; nicotine 28 versus 21 ng/mL;
      p < 0.001) despite smoking a similar number of cigarettes per day. Similar serum
      3'-hydroxycotinine (3HC) to cotinine ratios in both groups indicate that this
      difference was not due to differences in the rate of metabolism of nicotine or
      cotinine. By examining serum nicotine and 3HC/cotinine ratios in addition to
      cotinine, this study expands upon previous research that relied on cotinine as an
      indirect indicator for nicotine intake. Our data support the hypothesis that the
      increased serum nicotine and cotinine levels observed are attributable to an
      increased nicotine intake per cigarette in smokers with schizophrenia as compared
      to those without mental illness.

PMID- 15961289
TI  - The effect of written information on adherence to antibiotic treatment in acute
      sore throat.
AB  - A randomised clinical trial was conducted to establish whether written
      instructions, in addition to verbal ones, significantly improve adherence to
      antibiotic treatment for acute sore throat in comparison with verbal instructions
      only. Patients were selected by consecutive sampling at seven primary healthcare
      surgeries. The pill count average was 87.4+/-25.2% and it was higher in the
      intervention group (93.7+/-24.5%) than in the control group (81.1+/-24.5%) (P <
      0.05). Absolute risk reduction was 14% (95% confidence interval (CI), -3.77 to
      26.56); relative risk reduction was 24.9% (95% CI, -11.04 to 58.28); the number
      needed to treat was 8.77. Written instructions, in addition to verbal ones,
      significantly improve compliance with antibiotic treatment in tonsillitis of
      acute sore throat in comparison with verbal instructions only.

PMID- 15961290
TI  - Teacher reports of ADHD symptoms in Italian children at the end of first grade.
AB  - OBJECTIVE: To determine the prevalence of teacher-rated ADHD symptoms in Italian
      first-graders. METHOD: 1891 first-graders aged 6.6-7.4 years were evaluated using
      a 34-item DSM-IV-referenced ADHD teacher rating questionnaire which included all
      the 18 DSM-IV ADHD diagnostic criteria, some Oppositional-Defiant Disorder (ODD),
      Conduct Disorder (CD), depression and anxiety symptoms, and questions about the
      child's social and scholastic impairment. RESULTS: Criteria for ADHD were met in
      7.1% (n=135) of the subjects (10.4% males and 3.8% females), 3.5% with the
      Inattentive subtype, 2.3% with the Hyperactive/Impulsive subtype and 1.3% with a
      Combined subtype. Internalizing (depression and/or anxiety) symptoms were
      reported in 25.9% of the subjects with ADHD symptoms, 17% showed externalizing
      symptoms (ODD or CD), and 12.6% showed both. Comorbid symptoms were 10 times more
      frequent than in subjects without ADHD symptoms. Inattentive subtype and
      scholastic impairment were more frequent in females, Hyperactive/Impulsive
      subtype and social impairment were more frequent in males. CONCLUSIONS: Even
      though the real prevalence of ADHD in first graders is presumably lower than that
      found in the present study, this screening procedure might allow detecting those
      children who could benefit from referral for more comprehensive assessments.

PMID- 15961291
TI  - Quetiapine in the treatment of patients with resistant auditory hallucinations:
      two case reports with long-term cognitive assessment.

PMID- 15961292
TI  - Negative evidences in association between apolipoprotein E polymorphism and panic
      disorder.
AB  - The aim is to investigate the association between apolipoprotein E (ApoE) and
      panic disorder (PD). Genotyping 92 PD patients [Diagnostic Statistic Manual IV
      (DSM IV) criteria] and 174 controls no differences were found between both
      groups. Variation in the ApoE-gene was not associated with the development of PD.

PMID- 15961293
TI  - Size and burden of mental disorders in Europe--a critical review and appraisal of
      27 studies.
AB  - Epidemiological data on a wide range of mental disorders from community studies
      conducted in European countries are presented to determine the availability and
      consistency of prevalence, disability and treatment findings for the EU. Using a
      stepwise multimethod approach, 27 eligible studies with quite variable designs
      and methods including over 150,000 subjects from 16 European countries were
      identified. Prevalence: On the basis of meta-analytic techniques as well as on
      reanalyses of selected data sets, it is estimated that about 27% (equals 82.7
      million; 95% CI: 78.5-87.1) of the adult EU population, 18-65 of age, is or has
      been affected by at least one mental disorder in the past 12 months. Taking into
      account the considerable degree of comorbidity (about one third had more than one
      disorder), the most frequent disorders are anxiety disorders, depressive,
      somatoform and substance dependence disorders. When taking into account design,
      sampling and other methodological differences between studies, little evidence
      seems to exist for considerable cultural or country variation. Disability and
      treatment: despite very divergent and fairly crude assessment strategies, the
      available data consistently demonstrate (a) an association of all mental
      disorders with a considerable disability burden in terms of number of work days
      lost (WLD) and (b) generally low utilization and treatment rates. Only 26% of all
      cases had any consultation with professional health care services, a finding
      suggesting a considerable degree of unmet need. The paper highlights considerable
      future research needs for coordinated EU studies across all disorders and age
      groups. As prevalence estimates could not simply be equated with defined
      treatment needs, such studies should determine the degree of met and unmet needs
      for services by taking into account severity, disability and comorbidity. These
      needs are most pronounced for the new EU member states as well as more generally
      for adolescent and older populations.

PMID- 15961294
TI  - Subjective and neurovegetative changes in healthy volunteers and panic patients
      performing simulated public speaking.
AB  - Drug-free symptomatic panic patients, drug-treated nonsymptomatic patients and
      healthy controls were submitted to simulated public speaking. Subjective anxiety,
      cognitive impairment and discomfort measured by the visual analog mood scale as
      well as skin conductance level were higher in symptomatic patients than in
      controls at the beginning of the experimental session, nonsymptomatic patients
      lying in between. Subjective sedation, spontaneous fluctuations of skin
      conductance, heart rate and blood pressure were similar in the three groups.
      Preparation and performance of speech decreased sedation while increasing
      anxiety, cognitive impairment, level and fluctuations of skin conductance, heart
      rate and blood pressure. Anxiety, cognitive impairment and conductance level were
      less increased in symptomatic patients than in controls. Electrodermal activity,
      but not cardiovascular measures of sympathetic arousal correlated with
      anticipatory anxiety. Chronic treatment with serotonin uptake inhibitors
      attenuated the differences between panic patients and controls, supporting the
      participation of serotonin in panic disorder.

PMID- 15961295
TI  - Hemispheric lateralization patterns and psychotic experiences in healthy
      subjects.
AB  - The hypothesis that psychotic experiences in healthy subjects are associated with
      a dysfunction of the right hemisphere is supported by some, but not all,
      available studies. Differences in gender composition of study samples may explain
      in part the divergent findings. The present study was carried out in 42 healthy,
      right-handed university students. Scores on the Schizophrenia and Paranoia scales
      of the Minnesota Multidimensional Personality Inventory-2 were used in
      correlation analyses and to define a High- and a Low-Psychotic group. Brain
      Electrical Microstates and Low Resolution Electromagnetic Tomography (LORETA)
      source analyses of the auditory P300 (P3a and P3b) components of the event
      related potential, as well as a battery of neuropsychological tests, were used to
      assess hemispheric functioning. Scores on the Paranoia scale were positively
      associated with a leftward shift of the P3a topographic descriptors in females
      but not in males. When comparing High-Psychotic and Low-Psychotic females, a
      leftward shift of P3a descriptors and an increased cortical activation in left
      fronto-temporal areas were observed in the High-Psychotic group. Our results
      demonstrated gender-related differences in the pattern of hemispheric imbalance
      associated with psychotic experiences in healthy subjects.

PMID- 15961296
TI  - Influence of the aggregation state in solution on the supramolecular organization
      of adsorbed type I collagen layers.
AB  - In the last years, adsorbed collagen was shown to form layers with a
      supramolecular organization depending on the substrate surface properties and on
      the preparation procedure. If the concentration of collagen and the duration of
      adsorption are sufficient, fibrillar collagen structures are formed,
      corresponding to assemblies of a few molecules. This occurs more readily on
      hydrophobic compared to hydrophilic surfaces. This study aims at understanding
      the origin of such fibrillar structures and in particular at determining whether
      they result from the deposition of fibrils formed in solution or from the
      building of assemblies at the interface. Therefore, type I collagen solutions
      with an increasing degree of aggregation were prepared, using the "neutral-start"
      approach, by ageing pH 5.8 solutions at 37 degrees C for 15 min, 2 or 7 days. The
      obtained solutions were used to investigate the influence of collagen aggregation
      in solution on the supramolecular organization of adsorbed collagen layers, which
      was characterized by X-ray photoelectron spectroscopy and atomic force
      microscopy. Polystyrene and plasma-oxidized polystyrene were chosen as substrates
      for the adsorption. The size and the density of collagen fibrils at the interface
      decreased upon increasing the degree of aggregation of collagen in solution. This
      is explained by a competitive adsorption process between monomers and aggregates
      of the solution, turning at the advantage of the monomers. More aggregated
      solutions, which are thus depleted in free monomers, behave like less
      concentrated solutions, i.e. lead to a lower adsorbed amount and less fibril
      formation at the interface. This study shows that the supramolecular fibrils
      observed in adsorbed collagen layers, especially on hydrophobic substrates, are
      not formed in the solution, prior to adsorption, but are built at the interface,
      through the assembly of free segments of adsorbed molecules.

PMID- 15961297
TI  - The use of an in vitro dissolution and absorption system to evaluate oral
      absorption of two weak bases in pH-independent controlled-release formulations.
AB  - The aim of this study was to compare the oral absorption of two weak bases
      including their pH-independent controlled-release preparations using an in vitro
      evaluation system. This system is able to simulate dissolution of drugs, pH
      change and permeation of drugs through the epithelial cell membrane in the
      gastrointestinal tract. Albendazole-polymers solid dispersion and pH-independent
      sustained-release granules of dipyridamole were prepared by using a solvent
      method. Elution profiles and predicted absorption of these preparations in
      gastric pH conditions similar to those in healthy subjects and patients with
      achlorhydria were compared with those of a physical mixture and commercial
      tablets. When a physical mixture or commercial tablets were used, the elution
      profile and predicted absorption of both albendazole and dipyridamole were
      extremely pH-dependent. On the other hand, when a solid dispersion and granules
      were used, elution and predicted absorption were not affected by changes in pH of
      the flowing solution in a drug-dissolving vessel. These results are in agreement
      with the results of our previous in vivo study using gastric acidity-controlled
      rabbits. Our results suggest that this in vitro system is useful for the
      evaluation of oral absorption of pH-independent controlled-release preparations.

PMID- 15961298
TI  - Structures of the biological repeating units in the O-chain polysaccharides of
      Hafnia alvei strains having a typical lipopolysaccharide outer core region.
AB  - Earlier, the structures of the O-chain polysaccharides of the lipopolysaccharides
      (LPS) of a number of Hafnia alvei strains have been established. However, it
      remained unknown, which is the first and the last monosaccharide of the O-chain.
      This is defined by the structure of the so-called biological repeating unit (O
      unit), which is pre-assembled and then polymerised in the course of biosynthesis
      of bacterial polysaccharides by the Wzy-dependent pathway. Now we report on the
      structures of the O-units in 10 H. alvei strains. The LPS were cleaved by mild
      acid hydrolysis and oligosaccharide fractions IIIa and IIIb were isolated by gel
      chromatography subsequently on Sephadex G-50 and BioGel P-2 and studied by
      methylation analysis and NMR spectroscopy. Fraction IIIb was found to represent
      the core oligosaccharide containing a terminal upstream alpha-d-Glc-(1-->3)-alpha
      d-Glc or alpha-d-Gal-(1-->3)-alpha-d-Glc disaccharide in the outer region that is
      typical of H. alvei. Fraction IIIa consists of the LPS core with one O-unit
      linked by a 3-substituted beta-d-GalNAc residue (in strains PCM 1189 and PCM
      1546) or a 3-substituted beta-d-GlcNAc residue (in the other strains studied). In
      most strains examined the beta-configuration of the d-GlcNAc linkage in the first
      O-unit attached to the core is the same and in some strains is opposite to that
      found in the interior O-units of the O-chain polysaccharide. Various
      monosaccharides, including d-Glc, d-Gal, d-GlcA and acyl derivatives of 3-amino
      3,6-dideoxy-d-glucose or 4-amino-4,6-dideoxy-d-glucose, occupy the non-reducing
      end of the O-unit.

PMID- 15961299
TI  - [Action to be taken when facing one or more cases of whooping-cough].
AB  - The evolution of the epidemiology of pertussis, new licensed macrolides and
      vaccines, new recommendations for vaccination among adolescents and adults need
      an update of the French guidelines for prevention of the disease around one or
      grouped cases of the disease. A particular attention should be raised to the
      diagnosis of whooping cough in adults who are presently the main reservoir of
      Bordetella pertussis. Whooping cough in adults presents as an unexplained
      prolonged cough with nocturnal exacerbation witch accounts for most of the
      contaminations of young infants. A bacteriological confirmation of pertussis
      should be provided before implementation of preventive measures: culture and PCR
      are presently the gold standard for the diagnosis of pertussis in infants,
      children and even adults who have been coughing for less than 20 days. Later on,
      serology (Elisa, immuno-empreinte) is the only technique available, but cannot be
      interpreted if the patient has been vaccinated less than one year ago. Infants
      under three months should be admitted to hospital and every case submitted to
      respiratory isolation. Eviction from the community should be pronounced within
      the five first days following the onset of an effective antibiotic treatment. New
      macrolides should be favoured: clarithromycin for seven days or azithromycin for
      five days. Household contacts should be given the same prophylactic antibiotic
      treatment: children and adolescent not correctly immunized, parents of the index
      case as adults parents of not or not completely immunized infants. The
      vaccination program of the household should be updated. The same measures should
      be applied in case of grouped cases (at least two contemporary or consecutive
      cases in the same area). In that case, the Public Health System doctors should be
      involved in the investigation and the classification of the cases. The close
      contacts not or not completely immunized should be prescribed and antibiotic
      prophylaxis and an update of their vaccination program. Among the occasional
      contacts, high-risk people only should be treated. In the day care centres an
      antibiotic prophylaxis should be given to children who have received less than
      four vaccine shots against pertussis and to the personnel contact to the cases as
      well. In the schools, the antibiotic prophylaxis should be prescribed to all
      children of the classroom(s) not completely vaccinated and to the teacher(s) as
      well. In the boarding schools and institutions with handicapped children,
      antibiotic prophylaxis could be applied to every member if the pertussis vaccine
      coverage is at less than 50%. In hospitals, coughing personnel should wear masks
      and investigations towards pertussis should be performed in people with a more
      than seven day unexplained cough. Preventive measures should be applied in case
      of confirmation of pertussis.

PMID- 15961300
TI  - Structure and modeling studies of the carboxy-terminus region of human
      tropoelastin.
AB  - Elastin macromolecular assembly is a highly complex mechanism involving many
      steps including coacervation, cross-linking, and probably other (not known)
      phenomena. In past studies, it has been proposed that the C-terminal part of
      tropoelastin is also involved in this process and may play a key role in
      tropoelastin interactions with other proteins of the final elastic fibres
      scaffold. Presented here are the results of the biophysical studies
      (biospectroscopy, bioinformatics) of the C-terminal domain of tropoelastin. We
      report the detailed structures adopted by the oxidized (native) and reduced forms
      of the free synthetic peptide with sequence encoded by exon 36 of human
      tropoelastin (GGACLGKACGRKRK) and propose a dynamical interpretation of which
      structures may be involved in interactions with other extra-cellular matrix
      proteins. We also suggest that these structures may be retrieved in other
      proteins sharing a consensus sequence; however no definitive conclusion can be
      drawn here on a possible structure-function relationship.

PMID- 15961301
TI  - Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces
      apoptosis and up-regulates the GADD45, p53 and PPARgamma in human colon cancer
      Caco-2 cells.
AB  - Bitter gourd (Momordica charantia) seed oil (BGO) is a unique oil which contains
      9cis, 11trans, 13trans-conjugated linolenic acid (9c,11t,13t-CLN) at a high level
      of more than 60%. In this study, we investigated the anti-proliferative and
      apoptosis-inducing effects of free fatty acids prepared from BGO (BGO-FFA) using
      colon cancer Caco-2 cells. BGO-FFA and purified 9c,11t,13t-CLN remarkably reduced
      the cell viability of Caco-2. In Caco-2 cells treated with BGO-FFA, DNA
      fragmentation of apoptosis indicators was observed in a dose-dependent manner.
      The expression level of apoptosis suppressor Bcl-2 protein was also decreased by
      BGO-FFA treatment. The GADD45 and p53, which play an important role in apoptosis
      inducing pathways, were remarkably up-regulated by BGO-FFA treatment in Caco-2
      cells. Up-regulation of PPARgamma mRNA and protein were also observed during
      apoptosis induced by BGO-FFA. These results suggest that BGO-FFA rich in
      9c,11t,13t-CLN may induce apoptosis in Caco-2 cells through up-regulation of
      GADD45, p53 and PPARgamma.

PMID- 15961302
TI  - Free oxygen radical-induced lipid peroxidation and antioxidant in infants
      receiving total parenteral nutrition.
AB  - OBJECTIVE: Increased oxygen-derived free radical activity has been reported
      during total parenteral nutrition (TPN) in infants particularly linked to the fat
      infusion. It is possible that partial enteral feeding can ameliorate some of the
      complications of TPN. By this study we aimed to investigate free radical
      formation and antioxidant activity in term and preterm infants during TPN and/or
      enteral feeding. STUDY DESIGN: We had 6 groups of term and preterm infants made
      up of 10 patients each. Group I had only enteral feeding, Group II enteral plus
      parenteral feeding, Group III only parenteral feeding. Plasma malondialdehyde
      (MDA), superoxide dismutase (SOD), vitamin E and vitamin C levels were measured
      in all infants. Blood samples of infants receiving only TPN and TPN plus enteral
      feeding were measured on the 1st and 5th days, and 3h after the end of lipid
      infusion. RESULTS: There was no difference between the term and preterm infants
      in terms of MDA, SOD, vitamin C and E levels taken baseline and after parenteral,
      and enteral plus parenteral feeding on the 1st and 5th days. When 3 groups of
      both term and preterm infants were compared with each other none of the
      parameters showed a statistically significant difference. In addition, we
      compared baseline and 1st and 5th days of TPN therapy in both term and preterm
      infants fed only parenterally and enteral plus parenteral feedings. In term
      infants fed both parenterally and parenteral plus enterally, the MDA levels
      before TPN were significantly higher than that of the levels of patients on
      parenteral nutrition on the 5th day. On the 1st and 5th days of TPN therapy, the
      levels of vitamin C was significantly decreased, in term and preterm infants fed
      only parenterally, levels of vitamin E was increased, in term and preterm infants
      fed both parenterally and parenteral plus enterally. Also, when compared to their
      base line the SOD levels of the term infants detected on the 1st and 5th days
      were significantly high. CONCLUSION: Free radical production is increased by the
      administration of TPN and may be linked to its adverse effects. It may be assumed
      that long-term complications of preterm infants receiving TPN may be reduced by
      further strengthening the antioxidant capacities of the TPN solutions.

PMID- 15961303
TI  - Consequences of raising the height of a landfill in a water-deficient climate.
AB  - A large-scale field experiment has been carried out at the Coastal Park landfill
      which serves the City of Cape Town, South Africa. The landfill is unlined, and
      the City Council was under pressure from the central Government to cap and close
      the existing landfill and to establish an extension to the landfill with a lining
      to prevent the escape of leachate into the ground water. Measuring cells,
      installed to measure the rate of leachate flow from the landfill had shown that
      over a period of 9 years, from 1987 to 1995, leachate flow had averaged only 2%
      of rainfall. It therefore appeared possible, by increasing the moisture
      absorption capacity of the landfill, i.e., by increasing its height, to stop the
      leachate flow completely. If this could be achieved, there would be no need for a
      lining, and the raising would considerably extend the life of the landfill. The
      paper describes the experiment and its results, including the effects of the
      raising on leachate flow, settlement, leachate quality and the potential for
      polluting ground water, and the landfill's water balance.

PMID- 15961304
TI  - Constraining the connectivity of neuronal networks cultured on microelectrode
      arrays with microfluidic techniques: a step towards neuron-based functional
      chips.
AB  - In vitro culture of small neuronal networks with pre-defined topological features
      is particularly desirable when the electrical activity of such assemblies can be
      monitored for long periods of time. Indeed, it is hoped that such networks, with
      pre-determined connectivity, will provide unique insights into the
      structure/function relationship of biological neural networks and their
      properties of self-organization. However, the experimental techniques that have
      been developed so far for that purpose have either failed to provide very long
      term pattern definition and retention, or they have not shown potential for
      integration into more complex microfluidic devices. To address this problem,
      three-dimensional microfluidic systems in poly(dimethylsiloxane) (PDMS) were
      fabricated and used in conjunction with both custom-made and commercially
      available planar microelectrode arrays (pMEAs). Various types of primary neuronal
      cell cultures were established inside these systems. Extracellular electrical
      signals were successfully recorded from all types of cells placed inside the
      patterns, and this bioelectrical activity was present for several weeks. The
      advantage of this approach is that it can be further integrated with microfluidic
      devices and pMEAs to yield, for example, complex neuron-based biosensors or chips
      for pharmacological screening.

PMID- 15961305
TI  - Transcriptional regulation of aromatase in placenta and ovary.
AB  - Our goal is to define the cellular and molecular mechanisms for tissue- and cell
      specific, developmental and hormonal regulation of the human CYP19 (aromatase
      P450/P450arom) gene in estrogen-producing cells. In this article, we review
      studies using transgenic mice and transfected cells to identify genomic regions
      and response elements that mediate CYP19 expression in placenta and ovary, as
      well as to define the molecular mechanisms for O2 regulation of differentiation
      and CYP19 gene expression in human trophoblast cells in culture. We also
      highlight recent findings regarding LRH-1 versus SF-1 mRNA expression and
      cellular localization in the mouse ovary during the estrous cycle and various
      stages of pregnancy. Spatial and temporal expression patterns of mRNAs encoding
      these orphan nuclear receptors in comparison to those of P450arom and 17alpha
      hydroxylase/17,20-lyase mRNAs, suggest an important role of LRH-1 together with
      SF-1 in ovarian steroidogenesis.

PMID- 15961306
TI  - Delignification kinetics of corn stover in lime pretreatment.
AB  - Corn stover was pretreated with excess calcium hydroxide (0.5 g Ca(OH)(2)/g raw
      biomass) in non-oxidative and oxidative conditions at 25, 35, 45, and 55 degrees
      C. The delignification kinetic model of corn stover used three first-order
      reactions with following forms: W(L) = 0.09 x exp(-infinity x t) + 0.28 x exp(
      k(2) x t) + 0.63 x exp(-k(3) x t) in non-oxidative pretreatment; W(L) = 0.16 x
      exp(-infinity x t) + 0.27 x exp(-k(2) x t) + 0.57 x exp(-k(3) x t) in oxidative
      pretreatment. The first term corresponds to the initial phase, which is
      essentially infinite at the time scale of the reaction (weeks). The second and
      third terms correspond to the bulk and residual phases of delignification. The
      activation energies for delignification in the oxidative lime pretreatment
      reactions were estimated as 50.15 and 54.21 kJ/mol in the bulk and residual
      phases, respectively, which are similar to the Kraft delignification of bagasse,
      but much less than in Kraft delignification of wood.

PMID- 15961307
TI  - Effect of structural features on enzyme digestibility of corn stover.
AB  - Corn stover was pretreated with excess calcium hydroxide (0.5 g Ca(OH)2/g raw
      biomass) in non-oxidative and oxidative conditions at 25, 35, 45, and 55 degrees
      C. The enzymatic digestibility of lime-treated corn stover was affected by the
      change of structural features (acetylation, lignification, and crystallization)
      resulting from the treatment. Extensive delignification required oxidative
      treatment and additional consumption of lime (up to 0.17 g Ca(OH)2/g biomass).
      Deacetylation reached a plateau within 1 week and there were no significant
      differences between non-oxidative and oxidative conditions at 55 degrees C; both
      conditions removed approximately 90% of the acetyl groups in 1 week at all
      temperatures studied. Delignification highly depended on temperature and the
      presence of oxygen. Lignin and hemicellulose were selectively removed (or
      solubilized), but cellulose was not affected by lime pretreatment in mild
      temperatures (25-55 degrees C), even though corn stover was contacted with alkali
      for a long time, 16 weeks. The degree of crystallinity slightly increased from
      43% to 60% with delignification because amorphous components (lignin,
      hemicellulose) were removed. However, the increased crystallinity did not
      negatively affect the 3-d sugar yield of enzymatic hydrolysis. Oxidative lime
      pretreatment lowered the acetyl and lignin contents to obtain high digestibility,
      regardless of crystallinity. The non-linear models for 3-d hydrolysis yields of
      glucan (Y(g)), xylan (Y(x)), and holocellulose (Y(gx)) were empirically
      established as a function of the residual lignin (L) for the corn stover
      pretreated with lime and air.

PMID- 15961308
TI  - New natural injection-moldable composite material from sunflower oil cake.
AB  - Through a twin-screw extrusion process the native structure of sunflower oil cake
      was completely transformed (globular protein denaturation/texturization and husk
      fiber defibration) into a simpler matrix-fiber structure, as could be seen on SEM
      micrographs. Further chemical reduction of protein disulfide bridges greatly
      reduced the melt viscosity of the moistened composite that it could be injection
      molded. The molded specimens were tested and their tensile and flexural
      properties and water absorption calculated. Their water resistance appeared to be
      particularly high, and could be enhanced further after a thermal treatment (N2,
      200 degrees C). The proteic matrix seemed to behave like a natural thermoset
      resin. Sunflower oil cake could be used without any additives to make
      biodegradable, water resistant and exceptionally cheap materials.

PMID- 15961309
TI  - Dispersion modelling and measurement of emissions from the co-combustion of meat
      and bone meal with peat in a fluidised bed.
AB  - Due to the ban on meat and bone meal (MBM) as an animal feed, combustion with
      energy recovery has been considered a viable alternative usage for the mounting
      stocks of MBM. The effects of the co-combustion of MBM and peat on flue gas
      emissions and fluidisation were studied using a bubbling fluidised bed (BFB) test
      facility (20 kW). The dispersion of emissions such as nitrogen dioxide (NO2),
      sulphur dioxide (SO2), carbon monoxide (CO), hydrogen chloride (HCl) and
      particulates was investigated for a proposed site and compared to the relevant
      national and international regulations. Concentrations of NO2, CO and HCl were
      less than 10% of legislative and guideline thresholds while ground level
      concentrations of SO2 were also below relevant EU and world guidelines. The
      results indicate the potential for using MBM as a co-fuel with peat in a BFB
      while maintaining high air quality standards.

PMID- 15961310
TI  - Lp-PLA2 inhibitory activities of fatty acid glycerols isolated from Saururus
      chinensis roots.
AB  - (R)-Glycerol-monolinoleate 4 and (R)-glycerol-monostearate 5 were isolated from
      the ethyl acetate extracts of Saururus chinensis roots and (R)- or (S)-fatty acid
      glycerols 4 and 5 were synthesized for confirming their structures and evaluating
      their inhibitory activities against Lp-PLA(2). The (R)-4 and (S)-4 exhibited Lp
      PLA(2) inhibitory activities with IC(50) values of 45.0 and 52.0 microM,
      respectively.

PMID- 15961311
TI  - Rhodanine derivatives as inhibitors of JSP-1.
AB  - Dual-specificity phosphatases (DSPs) are a subclass within the protein tyrosine
      phosphatase family (PTPs). A series of rhodanine-based inhibitors was synthesized
      and shown to be novel, potent, and selective inhibitors against the DSP family
      member JNK-stimulating phosphatase-1 (JSP-1). Compounds of this class may be
      useful for the treatment of inflammatory and proliferative disorders.

PMID- 15961312
TI  - Two patients with 'Dropped head syndrome' due to mutations in LMNA or SEPN1
      genes.
AB  - Dropped head syndrome is characterized by severe weakness of neck extensor
      muscles with sparing of the flexors. It is a prominent sign in several
      neuromuscular conditions, but it may also be an isolated feature with uncertain
      aetiology. We report two children in whom prominent weakness of neck extensor
      muscles is associated with mutations in lamin A/C (LMNA) and selenoprotein N1
      (SEPN1) genes, respectively. This report expands the underlying causes of the
      dropped head syndrome which may be the presenting feature of a congenital
      muscular dystrophy.

PMID- 15961313
TI  - Destabilization of human balance control by static and dynamic head tilts.
AB  - To better understand the effects of varying head movement frequencies on human
      balance control, 12 healthy adult humans were studied during static and dynamic
      (0.14, 0.33, 0.6 Hz) head tilts of +/- 30 degrees in the pitch and roll planes.
      Postural sway was measured during upright stance with eyes closed and altered
      somatosensory inputs provided by a computerized dynamic posturography (CDP)
      system. Subjects were able to maintain upright stance with static head tilts,
      although postural sway was increased during neck extension. Postural stability
      was decreased during dynamic head tilts, and the degree of destabilization varied
      directly with increasing frequency of head tilt. In the absence of vision and
      accurate foot support surface inputs, postural stability may be compromised
      during dynamic head tilts due to a decreased ability of the vestibular system to
      discern the orientation of gravity. This instability may compound the risk of
      falling following recovery from balance disorders or adaptation to altered
      gravity conditions such as space flight. Thus, dynamic head tilts may improve the
      diagnostic sensitivity of computerized dynamic posturography, particularly for
      healthy subjects recovering from temporary balance control deficits.

PMID- 15961314
TI  - Divergent roles of murine neutrophil chemokines in hemorrhage induced priming for
      acute lung injury.
AB  - Neutrophil associated lung injury is identified with a variety of local and
      systemic priming insults. In vitro studies have shown that TNF-alpha mediated
      suppression of neutrophil apoptosis is due to the secretion of interleukin-8 (IL
      8), a human chemokine shown to alter neutrophil chemotaxis. Our initial in vitro
      antibody neutralization studies with neutrophil chemotactic proteins,
      keratinocyte-derived chemokine (KC) and macrophage inflammatory protein-2alpha
      (MIP-2alpha), mouse IL-8 homologues, indicate that MIP-2alpha but not KC appears
      to mediate TNF-alpha suppression of mouse neutrophil apoptosis. Therefore, we
      hypothesized that in vivo neutralization of KC or MIP-2alpha during an initial
      priming insult would produce differential effects on the extent of lung injury by
      restoring normal neutrophil apoptotic function. To assess this, mice were
      hemorrhaged followed with septic challenge at 24 h. Antibody against KC or MIP
      2alpha or a nonspecific IgG was given during resuscitation immediately following
      hemorrhage. Anti-MIP-2alpha treatment resulted in a significant reduction in lung
      tissue IL-6 and myeloperoxidase levels. Percentage of neutrophil apoptosis
      increased significantly in the anti-KC group. Tissue and plasma KC and MIP-2alpha
      were reduced in their respective treatment groups. These data suggest that KC and
      MIP-2alpha differ in their mediation of neutrophil function (apoptosis and
      chemotaxis) and contribution to the pathogenesis of lung injury following
      hemorrhage subsequent to sepsis.

PMID- 15961315
TI  - Aging and T cell development: interplay between progenitors and their
      environment.
AB  - Thymic involution is the hallmark of hematopoietic aging. Because T cell
      differentiation is a multistep process that occurs non-cell autonomously, aging
      defects can occur at multiple points along the developmental pathway, both in the
      T progenitors themselves and in the thymic stromal cells that support their
      development. Here we review the evidence for age-related thymopoiesis defects at
      key steps in the production of naive mature T cells, highlighting the importance
      of the interaction between stromal aging and progenitor aging.

PMID- 15961316
TI  - Toenail and plasma levels as biomarkers of selenium exposure.
AB  - PURPOSE: Both blood and toenail selenium are used to assess selenium exposure in
      epidemiologic studies. Little is known about the relationship of these biomarkers
      with each other or about whether there are differences in the relationships of
      these biomarkers with diet, supplement use, or participant characteristics.
      METHODS: Data are from 220 participants in a large cohort study of supplement use
      and cancer risk. Measures of selenium exposure included supplement use (current
      and 10-year) from a self-administered questionnaire, an inventory of currently
      used supplements (multivitamins and single supplements), dietary intake from a
      food frequency questionnaire (FFQ), and selenium concentration in toenails and
      plasma. RESULTS: Plasma and toenail selenium concentrations were significantly
      correlated (r=.56 [95% confidence interval: .46, .64]). Supplemental selenium was
      the strongest predictor of both selenium biomarkers, and these associations were
      slightly stronger when based on the supplement inventory and 10-year self
      reported use compared to current self-reported use. Correlations of current and
      10-year questionnaire dose and inventory dose with toenail selenium were .26,
      .36, and .33; for plasma selenium, these were .27, .36, and .36. Neither dietary
      selenium nor any participant characteristics, except smoking, was related to
      either biomarker. Current smokers had lower toenail, but not plasma, selenium
      levels compared to nonsmokers (.89 versus 1.03 microg/g, p = .03); however, the
      difference was not significant after control for supplement use (p = .09).
      CONCLUSIONS: Both toenail and plasma selenium levels similarly reflect selenium
      intake exposure. There do not appear to be independent associations of toenail or
      plasma selenium with FFQ-derived selenium intakes, health-related behaviors, or
      demographic characteristics.

PMID- 15961317
TI  - Accessing a new medication in Germany: a novel approach to assess a health
      insurance-related barrier.
AB  - PURPOSE: Knowledge of the existence, position, and magnitude of barriers to
      equitable healthcare is an important consideration in shaping healthcare
      policies. METHODS: The authors developed a novel three-dimensional person-time
      related hurdle model and followed a cohort of 7358 statutorily (SHI) and 457
      privately health insured (PHI) patients with migraine headaches at 377 primary
      care practices (MediPlus, IMS Health) in the second to fourth year of the
      HealthCare Structural Reform Act in Germany. RESULTS: For SHI compared with PHI
      migraine patients, there was a hurdle to receiving sumatriptan at all (2.4-fold
      lower hazard, 95% confidence interval, 1.8-3.2). Among patients who received
      sumatriptan, frequency and intensity of use differed only minimally between SHI
      and PHI patients. CONCLUSIONS: These findings have implications for healthcare
      researchers and healthcare policies. The framework extends traditional hurdle
      models and can serve as a model for quantifying barriers to receipt of services
      under different funding policies.

PMID- 15961318
TI  - Cloning the prophenoloxidase cDNA and monitoring the expression of proPO mRNA in
      prawns (Macrobrachium rosenbergii) stimulated in vivo by CpG
      oligodeoxynucleotides.
AB  - The prophenoloxidase (proPO) system forms the basis of the non-specific defence
      system in crustaceans. The aim of this study was to develop an RT-PCR procedure
      to determine proPO gene expression. We used several degenerate primers designed
      from the conserved regions in amino acid sequences of proPOs from other species
      to clone the possible cDNA(s) from the haemocytes of the prawn Macrobrachium
      rosenbergii. One DNA fragment, 2016 bp long, was cloned by a combination of
      reverse transcriptase-polymerase chain reaction (RT-PCR) and rapid amplification
      of cDNA ends (3'/5'-RACE). This fragment could encode a putative polypeptide with
      671 amino acids. Further analysis showed that this putative polypeptide contained
      six histidine residues and a thiol ester-like motif (GCGWPRHM) just like the
      structural features of proPOs from the shrimp Penaeus monodon. A partial fragment
      of the sequence with 934 bp containing three histidine residues and the thiol
      ester-like motif was used as a target to monitor the activation of the proPO gene
      by the semi-quantitative RT-PCR analysis. The result showed that the highest
      level of proPO mRNA was detected at 1h after in vivo injection with 5 microg of
      CpG oligodeoxynucleotide 2006 per prawn; in the same experiment, the highest PO
      activity was detected at 6 h after injection. In the control, a continuous and
      slow elevation of PO activity was observed during the experimental period, but
      such elevation of proPO mRNA was not observed. From our previous study and the
      time course of gene expression of proPO and enzymatic activity of PO in this
      study, it can be concluded that the enhancement effect was through its
      transcriptional level, its translational level and then its post-translational
      level sequentially. These results suggest that, both for reliability, sensitivity
      and for the timing of sampling, the change in proPO mRNA is more useful than the
      PO activity in monitoring the activation of the proPO non-specific defence system
      of prawns after treatment with stimulants.

PMID- 15961319
TI  - Effect of Achyranthes aspera on the immunity and survival of Labeo rohita
      infected with Aeromonas hydrophila.
AB  - Achyranthes aspera seed was incorporated in the diets (at 0.01%, 0.1% and 0.5%)
      of Labeo rohita, rohu fingerlings (3.0+/-0.4 g). After 2 weeks, the fish were
      immunized with heat-killed Aeromonas hydrophila, and after a further 2 weeks the
      rohu were experimentally infected with Aeromonas hydrophila (ATCC 49140). After 7
      days blood and serum were sampled to determine superoxide anion production,
      bactericidal activity, lysozyme, serum protein, albumin, globulin, serum
      glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase
      (SGPT) and alkaline phosphatase (ALP). Superoxide anion production, serum
      bactericidal activity, lysozyme, ALP, serum protein, albumin:globulin ratio (A/G)
      were enhanced in Achyranthes treated groups compared to the control group. SGOT
      and SGPT levels were elevated in control group, but in Achyranthes treated groups
      the levels were similar to the uninfected-control group. Higher cumulative
      mortalities were observed in the control group (77%) up to day-9 after infection.
      This gradually decreased with increasing dose of Achyranthes, 66% mortality in
      0.01% group, 57% mortality in 0.1% group and 28% mortality in 0.5% group. These
      results indicate that Achyranthes aspera stimulates immunity and increases
      resistance to infection in L. rohita.

PMID- 15961320
TI  - Husbandry stress during early life stages affects the stress response and health
      status of juvenile sea bass, Dicentrarchus labrax.
AB  - In aquaculture management it is important to establish objective criteria to
      assess health and welfare of the fish. Here we show that European sea bass
      (Dicentrarchus labrax) confronted with husbandry-associated stress (tank
      cleaning, i.e. scrubbing, and water temperature variation) during early life
      stages show poorer survival and disease resistance as juveniles. We evaluated
      several parameters for stress (plasma cortisol, glucose and lactate, hydromineral
      status), growth performance, the immune response (plasma IgM levels) and the
      effects of a nodavirus challenge. Principal component analysis allowed the
      establishment of a stress panel including plasma cortisol, osmolality, IgM levels
      and weight. Sea bass juveniles reared during early life in high and constant
      temperature perform best in terms of stress-related parameters assessed by
      principle component analysis. Variable water temperature triggers dramatic
      changes in plasma cortisol, osmolality, IgM levels, body weight and
      susceptibility to nodavirus that suggest a strong and prolonged activation of the
      HPI axis. Scrubbing induces some disturbances typical for mild short-term, acute
      stress, viz. increased plasma osmolality and decreased IgM levels, but does not
      affect plasma cortisol, growth or susceptibility to nodavirus of sea bass. Our
      data fit well with the concept of allostasis. We discuss the relevance of our
      work for sea bass aquaculture.

PMID- 15961321
TI  - Deriving the optimal number of events for an event-related fMRI study based on
      the spatial extent of activation.
AB  - Event-related fMRI is a powerful tool for localising psychological functions to
      specific brain areas. However, the number of events required to produce stable
      activation maps is a poorly investigated and understood problem. Huettel and
      McCarthy [Huettel, S.A., McCarthy, G., 2001. The effects of single-trial
      averaging upon the spatial extent of fMRI activation. NeuroReport 12, 2411-2416]
      have shown that the spatial extent of activation increases monotonically with the
      number of events in an analysis. In the present paper, this result is replicated
      and shown to be a consequence of the cross-correlation technique used to
      determine active voxels and does not hold, for example, for a GLM analysis.
      Another analysis technique, that does not depend on goodness-of-fit to the data,
      is also proposed. This technique calculates an impulse response function (IRF)
      for each voxel, finds the best fitting haemodynamic shape to the IRF and returns
      an area-under-the-curve (%AUC) activation measure. Using spatial extent as a
      measure, asymptotic behaviour is evident after as few as 25 events for the %AUC
      analysis technique in a finger-tapping task with non-overlapping haemodynamic
      responses and for both the GLM and %AUC techniques in a similar task that allows
      responses to overlap. The experimental validity of the %AUC technique to identify
      active brain regions while minimising false positive levels is demonstrated in a
      group study with 25 participants.

PMID- 15961322
TI  - Word and non-word reading: what role for the Visual Word Form Area?
AB  - The putative role of the so-called Visual Word Form Area (VWFA) during reading
      remains under debate. For some authors, this region is specifically involved in a
      pre-lexical processing of words and pseudowords, whereas such specificity is
      challenged by others given the VWFA involvement during both non-word reading and
      word listening. Here, we further investigated this issue, measuring BOLD
      variations and their lateralization with fMRI during word and non-word reading,
      in order to evaluate the lexicality effect, and during reading and listening of
      words, in order to evaluate the impact of stimulus delivery modality on word
      processing networks. Region of interest (ROI) analysis was first performed in
      three target areas: 1-VWFA as defined by a meta-analysis of the word reading
      literature, 2-a middle temporal area (T2) found co-activated by both word reading
      and listening, 3-an inferior occipital area (OI) belonging to the unimodal visual
      cortex of the inferior occipital gyrus. VWFA activity was found not different
      between word and non-word reading but was more leftward lateralized during word
      reading due to a reduction of activity in the VWFA right counterpart. A similar
      larger leftward lateralization during word reading was also uncovered in the T2
      ROI but was related to a larger left side activity. Such a lexicality effect was
      not observed in the OI ROI. By contrast, BOLD increases during listening were
      restricted to the left VWFA and T2 ROIs. Voxel-based analysis (SPM99) showed that
      semantic areas were more active during word than non-word reading and co
      activated by both reading and listening, exhibiting a left lateralized activity
      in all tasks. These results indicate that the left VWFA would be the place where
      visual and verbal representations bind under the control of left semantic areas.

PMID- 15961323
TI  - Altered generation of spontaneous oscillations in Alzheimer's disease.
AB  - Slowing of spontaneous alpha oscillations and an anterior shift of a source of
      alpha activity (8-13 Hz) have been consistently reported in the EEG studies of
      Alzheimer's disease (AD). It is unknown whether these changes are associated with
      a gradual shift in location and frequency of existing sources or rather with the
      involvement of a new set of oscillators. We addressed this question by applying
      source modeling (minimum current estimates, MCE) to spontaneous alpha activity
      recorded with a 306-channel MEG system from eleven non-medicated AD patients with
      mild to moderate cognitive impairment and twelve age-matched controls during the
      eyes-closed session. AD patients had predominant lower alpha band sources in the
      temporal regions, whereas in the controls, robust alpha sources were found near
      the parieto-occipital sulcus. Activation within the parieto-occipital region was
      significantly weaker, and activation in the right temporal area was significantly
      enhanced in the AD patients. These results suggest an increased temporal-lobe
      contribution coinciding with parieto-occipital deficits. We propose that MCE,
      which provides simultaneous mapping of several oscillatory sources, might be
      useful for detecting neurophysiological abnormalities associated with AD in
      combination with other neuropsychological and neurological measures.

PMID- 15961324
TI  - Challenges and lessons learned since implementation of the safety pharmacology
      guidance ICH S7A.
AB  - The International Conference on Harmonization, Topic S7A guidance (ICH S7A) on
      safety pharmacology for human pharmaceuticals has been in effect for 3 years in
      Europe, the United States and Japan. Surveys of the pharmaceutical industry,
      regulatory agencies and the audience attending the 4th Annual Meeting of the
      Safety Pharmacology Society have helped identify and address areas of
      controversy, as well as those challenges that have emerged since implementation
      of the guidance worldwide. Overall, ICH S7A has been successfully implemented.
      The guidance provides for "Good Laboratory Practice" compliant "safety
      pharmacology core battery" of studies that are generally performed prior to first
      administration to humans. The approach is science-driven and specifies the use of
      robust and sophisticated in vitro and/or in vivo assays. There are, however, some
      areas that require further refinement/clarification such as the specifics of
      study design including the selection of dose/concentration, choice of species,
      modeling of the temporal pharmacodynamic changes in relation to pharmacokinetic
      profile of parent drug and major metabolites, use of an appropriate sample size,
      statistical power analysis as a means of demonstrating the sensitivity of the
      model system, testing of human-specific metabolites and demonstrating not only
      the model's sensitivity, but also its specificity for predicting adverse events
      in humans. There was also discussion of when these studies are needed in relation
      to the clinical development plan. Representatives from the pharmaceutical
      industry and regulatory agencies see the implementation of ICH S7A as a major
      step forward towards identifying the risk to Phase 1 and 2 volunteers and
      patients. It remains to be seen, however, whether and in what ways the ICH S7A
      based strategy will contribute to the modification of the integrated risk
      assessment during the latter stages of clinical development or once drugs have
      been introduced to the marketplace.

PMID- 15961325
TI  - Cardiovascular parameters in anaesthetized guinea pigs: a safety pharmacology
      screening model.
AB  - INTRODUCTION: Assessment of cardiovascular functions in vivo is part of the core
      battery of guideline ICH S7A and is thereby required by regulatory authorities.
      The haemodynamic effects of repeated intravenous administrations of reference
      compounds were analyzed in order to validate the guinea pig model for safety
      pharmacology studies under GLP conditions. METHODS: Male guinea pigs (n=54,
      weighing 565-762 g) were anaesthetized using 1.5 g/kg, i.p., urethane. Systolic
      arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), heart
      rate (HR), left ventricular pressure (LVP), cardiac contractility (dp/dt(max)),
      and ECG (RR, QT, and QTc intervals) were recorded continuously. Animals received
      vehicle i.v. followed by cumulative doses of reference compounds. RESULTS:
      Vehicle did not produce any relevant changes, either in cardiovascular or ECG
      parameters. Isoproterenol caused a rapid and significant increase in HR, LVP, and
      dp/dt(max), in contrast to a dose-dependent decrease in SAP and DAP. Epinephrine
      led to a potent increase in all cardiovascular parameters. Nifedipine produced a
      slight decrease in HR and LVP, and a potent decrease in blood pressure and
      dp/dt(max). Verapamil caused a dose-dependent decrease in all cardiovascular
      parameters. Ouabain resulted in a significant increase in SAP, DAP, LVP, and
      dp/dt(max); ECG showed an atrioventricular block and arrhythmia. Terfenadine,
      cisapride, and sotalol prolonged QT and QTc intervals, whereas vehicle and the
      other tested compounds did not produce any prolongation of the QTc interval.
      DISCUSSION: Our results on HR, blood pressure, and ECG obtained after i.v.
      administration of reference compounds show the usefulness of the guinea pig in
      assessing cardiovascular safety. The anaesthetized guinea pig allows the
      measurement of cardiac contractility and the use of doses higher than in
      conscious animals. Using this animal model, several cardiovascular parameters can
      be recorded simultaneously at a modest cost in terms of test compound and the
      number of animals required.

PMID- 15961326
TI  - Topiramate monotherapy as broad-spectrum antiepileptic drug in a naturalistic
      clinical setting.
AB  - Topiramate was assessed in an open-label trial as broad-spectrum antiepileptic
      monotherapy, independently from the epilepsy type or syndrome. Adults and
      children aged 2 years and older, who were diagnosed with epilepsy within the last
      5 years, treatment-naive or failing prior treatment with one antiepileptic drug
      (AED), received individually adjusted doses of topiramate, after escalation to
      100mg/day over 4 weeks (maximum 400mg/day) or 3mg/kg/day over 6 weeks (maximum 9
      mg/kg/day), respectively. Patients were followed for >or=7 months and optionally
      up to a maximum of 13 months. Data were analysed for all patients (n=692), as
      well as for focal (n=421) and generalized epilepsies (n=148). The median
      topiramate dose used was 125 mg/day in adults and 3.3mg/kg/day in children
      (<or=12 years). Overall, 80% of patients completed the 7-month study. During this
      period, 44.3% were seizure-free, while 76.3% achieved >or=50% reduction in mean
      monthly seizure frequency. Patients with focal and generalized epilepsies alike
      responded to treatment (73.9 and 83.8% with at least 50% seizure reduction):
      39.4% of patients with focal epilepsy and 61.5% of those with generalized
      epilepsy were seizure-free. The mean monthly seizure frequency was significantly
      reduced versus baseline at all visits (p<0.001). Similar response rates were
      obtained from the 237 patients completing the 1-year observation period. During
      the mandatory 7-month period of study, 8.8% of patients reported insufficient
      tolerability as a reason for dropout. The most frequent adverse event was
      paraesthesia. Our results support findings that emerge from controlled studies
      that topiramate is effective and well tolerated when used as initial or second
      monotherapy. They also suggest that in a naturalistic setting, overall good
      retention on treatment and seizure freedom are observed at low doses in a broad
      spectrum of epilepsies.

PMID- 15961327
TI  - The role of subchondral bone resorption pits in osteoarthritis: MMP production by
      cells derived from bone marrow.
AB  - OBJECTIVE: The vascular invasion of bone marrow tissue into the subchondral plate
      is often observed in articular cartilage and we named it the subchondral bone
      absorption pit; however, its implication in the pathogenesis of osteoarthritis
      (OA) has been poorly understood. The purpose of this study was to evaluate its
      characteristics and roles in osteoarthritic conditions. METHODS: Articular
      cartilage specimens from 11 patients with medial type knee OA and 7 non-arthritic
      cadavers were analyzed with HE staining. OA sections were stained with safranin
      O, TRAP (tartrate resistant acid phosphatase) and immunostained with anti-MMP-1,
      MMP-3, MMP-13, vitronectin receptor (VNR)-alpha chain, vimentin and bone
      morphogenic protein (BMP) 2/4 antibodies. RESULTS: Subchondral bone resorption
      pits were classified according to the extent of invasion: pits with bone marrow
      tissue were located within uncalcified cartilage below the tidemark in grade I
      and invaded beyond the tidemark in grade II, while no invasion was seen in grade
      0. Grade II pits were dominant in OA compared to non-arthritic joints, especially
      medial condyles. Proteoglycan detected with safranin-O staining was lost around
      the tip of grade II pits and the density of pits was related to the modified
      Mankin Score. Cells in pits expressed vimentin, MMP-1, MMP-3 and MMP-13. Some
      polynuclear cells co-expressed VNR-alpha chain and MMP-13, whereas pits showed
      reparative features expressing BMP. CONCLUSION: These results suggest that
      subchondral bone resorption pits contribute to cartilage degradation by
      expressing matrix metalloproteinases in OA.

PMID- 15961328
TI  - Considerations in measuring cartilage thickness using MRI: factors influencing
      reproducibility and accuracy.
AB  - OBJECTIVE: The primary goal of this study was to describe and evaluate conditions
      that could influence the precision and accuracy of measuring in vivo cartilage
      thickness in the weight bearing regions of the knee from magnetic resonance
      imaging (MRI). DESIGN: Three-dimensional (3D) models of the femoral cartilage
      were created from segmented MR images. The weight bearing regions on femoral
      cartilage were selected for the portion of the tibiofemoral joint that sustains
      contact during walking. Six regions of interest (three on each condyle) were
      located on the femur. Average cartilage thickness was calculated over each
      region. The sensitivity of the precision of the measurements to observer
      variability was evaluated using intra- and inter-observer reproducibility tests
      of cartilage thickness measurements from the MRI-derived 3D models. In addition,
      the quantitative influence of a rule-based protocol for segmentation was
      evaluated using the inter-observer reproducibility protocol. Accuracy tests were
      conducted on porcine knees by comparing 3D models from MR images and laser scans
      across weight bearing and non-weight bearing regions. RESULTS: The precision was
      substantially better for the intra-observer tests (Coefficient of variation (CV)
      = 1-3%) than the inter-observer tests. Adding a rule-based protocol reduced
      variability in inter-observer tests substantially (CV = 6.6% vs 8.3%). Accuracy
      tests showed that the central and weight bearing regions on each condyle were
      more accurate than boundary and non-weight bearing regions. In addition, these
      results indicate that care should be taken when determining cartilage thickness
      of weight bearing regions with cartilage degenerations, since the thickness of
      thinner cartilage can be systematically overestimated in MR images. CONCLUSIONS:
      A rule-based approach can substantially increase inter-observer reproducibility
      when measuring cartilage thickness from multiple observers. This improvement in
      inter-observer reproducibility could be an important consideration for
      longitudinal studies of disease progression. In quantifying cartilage thickness,
      central and weight bearing regions on each condyle can provide more accurate
      measurement than boundary and non-weight bearing regions with average accuracy of
      +/-0.2-0.3 mm. An important finding of this study was that the weight bearing
      regions, which are usually of the greatest clinical interest, were measured most
      accurately by sagittal plane imaging.

PMID- 15961329
TI  - Expression and regulation of Toll-like receptor 2 by IL-1beta and fibronectin
      fragments in human articular chondrocytes.
AB  - OBJECTIVE: The objective of this study was to examine expression and regulation
      of Toll-like receptor 2 (TLR2) in human articular chondrocytes. METHODS: Human
      articular chondrocytes were enzymatically isolated from normal and osteoarthritic
      knee cartilage. Immunohistochemistry, Western blotting, and reverse transcriptase
      polymerase chain reaction (RT-PCR) were used to assess the expression of toll
      like receptors. Following stimulation of chondrocytes in vitro by IL-1beta and
      fibronectin proteolytic fragments, the relative levels of mRNA for TLR2 were
      determined by quantitative real-time PCR. MyD88 activation and nuclear factor
      kappaB (NF-kappaB) translocation were evaluated by immunoprecipitation and
      electrophoretic mobility shift assay, respectively. RESULTS: Human articular
      chondrocytes mainly expressed TLR1, 2, 5 by RT-PCR. Protein expression of TLR2
      was also identified in adult human articular cartilage. TLR2 was upregulated
      following IL-1beta and fibronectin proteolytic fragments stimulation in primary
      cultures of osteoarthritic articular chondrocytes. Fibronectin proteolytic
      fragments-induced TLR2 upregulation involved an IL-1beta autocrine/paracrine
      pathway. CONCLUSIONS: TLR2 is expressed in human articular cartilage and is
      upregulated by proarthritic agents including IL-1beta and fibronectin fragments.
      Signaling through TLR is a novel pro-inflammatory mechanism in osteoarthritis and
      targeting of these signaling pathways may be of value in treatment of
      degenerative joint disease.

PMID- 15961330
TI  - Na+,K(+)-ATPase activity is reduced in hippocampus of rats submitted to an
      experimental model of depression: effect of chronic lithium treatment and
      possible involvement in learning deficits.
AB  - This study was undertaken to verify the effects of chronic stress and lithium
      treatments on the hippocampal Na+,K(+)-ATPase activity of rats, as well as to
      investigate the effects of stress interruption and post-stress lithium treatment
      on this enzyme activity and on spatial memory. Two experiments were carried out;
      in the first experiment, adult male Wistar rats were divided into two groups:
      control and submitted to a chronic variate stress paradigm, and subdivided into
      treated or not with LiCl. After 40 days of treatment, rats were killed, and
      Na+,K(+)-ATPase activity was determined. In the second experiment, rats were
      stressed during 40 days, and their performance was evaluated in the Water Maze
      task. The stressed group was then subdivided into four groups, with continued or
      interrupted stress treatment and treated or not with lithium for 30 additional
      days. After a second evaluation of performance in the Water Maze, rats were
      killed and Na+,K(+)-ATPase activity was also measured. Results showed an
      impairment in Na+,K(+)-ATPase activity and in Water Maze performance of
      chronically stressed rats, which were prevented by lithium treatment and reversed
      by lithium treatment and by stress interruption. These results suggest that the
      modulation of Na+,K(+)-ATPase activity may be one of the mechanisms of action of
      lithium in the treatment of mood disorders.

PMID- 15961331
TI  - Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy
      homeostasis.
AB  - The finding of orexin (hypocretin) deficiency in patients with narcolepsy
      suggests that this hypothalamic neuropeptide plays a crucial role in regulating
      and maintaining sleep/wakefulness states and energy homeostasis. Orexin might be
      especially important for stabilization of behavioral states, because the major
      symptom in narcolepsy is instability of each behavioral state, which results in
      sleep/wakefulness fragmentation. The efferent and afferent systems of orexin
      neurons suggest interactions between these cells and arousal/sleep-wakefulness
      centers in the brainstem as well as important feeding centers in the
      hypothalamus. Electrophysiological studies have shown that orexin neurons are
      regulated by monoamines and acetylcholine as well as metabolic cues, including
      leptin, glucose, and ghrelin. Thus, orexin neurons have the requisite functional
      interactions with hypothalamic feeding pathways and monoaminergic/cholinergic
      centers, and provide a critical link between peripheral energy balance and the
      central mechanisms that coordinate sleep/wakefulness and motivated behavior such
      as food seeking.

PMID- 15961332
TI  - Development, advances and applications of diagnostic ultrasound in animals.
AB  - Ultrasound has many industrial applications but it was first introduced as a
      medical diagnostic aid in the 1940s with its first veterinary application, the
      detection of ovine pregnancy, being reported in 1966. Since then, improvements in
      equipment quality combined with an increased awareness of the benefits of
      ultrasound as an imaging technique have led to its widespread use in the
      veterinary field. Recent advances in computer technology have significantly
      influenced equipment design and the miniaturization of transducers allows intra
      operative and intra-vascular applications. Software advances have improved the
      ability to manipulate and process data, leading to an increased amount of
      information being obtained from each examination and the advent of 'remote
      diagnosis'. Ultrasound guided interventional techniques can now be used for
      diagnostic or therapeutic purposes. Many of these developments have been
      introduced by equipment manufacturers but have found specific applications in the
      veterinary field. Ultrasound is currently employed in a very diverse range of
      situations, not just as a diagnostic tool in the routine clinical workup of a
      range of species, but also for disease screening, conservation projects,
      commercial services, herd management and clinical research.

PMID- 15961333
TI  - Reproductive performance of gilts following an outbreak of acute proliferative
      enteropathy due to Lawsonia intracellularis.
AB  - After a sudden outbreak of clinical porcine proliferative enteropathy (PPE) in a
      Croatian indoor breeding unit, the farm experienced decreased reproductive
      performance of Lawsonia intracellularis positive gilts. Conception-, farrowing-,
      and adjusted farrowing rates were lower (P<0.001) in gilts with positive L.
      intracellularis status. The number of live born and the total born litter size
      were significantly lower (P<0.001) in L. intracellularis positive gilts compared
      to seronegative ones. No differences were observed in numbers of stillborn and
      mummified pigs between the L. intracellularis positive and negative gilts.

PMID- 15961334
TI  - The management and welfare of some common ovine obstetrical problems in the
      United Kingdom.
AB  - This review approaches sheep welfare during the periparturient period from a
      veterinary practitioner viewpoint. At the most fundamental husbandry level, the
      general hygiene standards adopted on many sheep farms in the United Kingdom (UK)
      during the lambing period are unacceptable and require urgent improvement.
      Concerns also arise from obstetrical conditions attended by farmers which cause
      pain that can be identified using clinical criteria such as altered demeanour and
      behaviour of the ewe, and the presence of inflammation of the reproductive tract.
      Reduced production is evidenced by poor milk production and hungry lambs, the
      necessity to rear such lambs artificially and, in neglected cases, death of the
      ewe and her lambs. The correction of dystocia, periparturient vaginal, uterine
      and rectal prolapses is greatly facilitated after epidural injection of
      lignocaine, or a combination of xylazine and lignocaine administered by a
      veterinary surgeon. However, the perceived high professional fees charged for
      these services, and for Caesarean operations, result in few sheep receiving
      veterinary care, with such neglect directly contributing to poor welfare
      standards and an increased ewe mortality rate during the periparturient period.
      Whilst ending any welfare concern, the destruction of ewes rather than requesting
      veterinary services purely for economic reasons is a disturbing trend in sheep
      production in the UK and raises concerns regarding positive interaction between
      veterinary practitioner and farmer. In this article, veterinary treatments which
      provide effective analgesia are described and costed for obstetrical conditions
      in sheep. Recommended treatment protocols are described for the common
      obstetrical problems in sheep. In addition to appropriate treatment of
      obstetrical problems and alleviation of pain, if veterinary involvement could
      reduce ewe periparturient mortality from estimated figures of 4-2% this would
      save an estimated 400,000 ewes annually in the UK. Sheep welfare could be
      considerably improved by practising veterinarians providing practical instruction
      to small groups of clients with funding provided by government agencies.

PMID- 15961335
TI  - High frequency single-mode resonators for EPR spectroscopy enabling rotations of
      the sample about two orthogonal axes.
AB  - A novel single-mode resonant structure which enables the rotation of the sample
      about two orthogonal axes is investigated in view of electron paramagnetic
      resonance applications. The proposed solution is based on cylindrical non
      radiative resonators laterally loaded by the sample holder. The resulting
      structure can still operate in non-radiative regime, although no longer
      rotationally invariant. These theoretical predictions, based on symmetry
      considerations, are confirmed by means of a finite element numerical modelling.
      Theoretical and computational results are then substantiated by experimental
      investigations at millimeter wavelengths. As a result, a single-mode resonator
      which enables all the relevant rotations of the sample is demonstrated at
      millimeter wavelengths for the first time. In this resonator the intensity of the
      microwave field on the sample and its orientation with respect to the static
      magnetic field can be kept constant during the rotations. Therefore, a complete
      characterization of anisotropic systems is possible at the highest sensitivity,
      without the need of split-coil magnets. Possible applications at very high
      frequencies are discussed.

PMID- 15961336
TI  - Milk composition of a free-ranging African elephant (Loxodonta africana) cow
      during early lactation.
AB  - Only one study previously reported comprehensively on the composition of African
      elephant's (Loxodonta africana) milk that was collected from 30 dead animals. In
      the current study milk was obtained from a tame but free-ranging African elephant
      cow without immobilization during the period when she was 4-47 days postpartum.
      At the respective collection times the nutrient content was 21.8 and 25.0 g
      protein; 56.0 and 76.0 g fat; 71.1 and 26.0 g sugars per kilogram of milk. The
      protein fraction, respectively, consisted of 10.0 and 14.0 g caseins/kg milk and
      of 11.8 and 11 g whey proteins/kg milk. During lactation the lactose content
      dropped from 52.5 to 11.8 g/kg milk, while the oligosaccharide content increased
      from 11.8 to 15.2 g/kg milk. The oligosaccharide was characterized as a
      galactosyllactose, which is digestible by cellulase. Electrophoresis and
      identification of protein bands showed a similar migrating sequence of proteins
      as seen in cow's milk, but some of the corresponding proteins were less
      negatively charged. The lipid fraction contains a high content of capric and
      lauric acids, approximately 60% of the total fatty acids, and low content of
      myristic, palmitic and oleic acids.

PMID- 15961337
TI  - Enzymatic and feeding behaviour of Argopecten purpuratus under variation in
      salinity and food supply.
AB  - Argopecten purpuratus is a bivalve filter feeder inhabiting protected areas of
      the Peruvian coastline and northern and central Chile. The species is
      commercially valuable and the natural stocks are over-exploited in Chile, mainly
      in the central region. Expansion of aquaculture farms to the geographically
      protected coastline of southern Chile is a potential solution to this problem.
      So, the objective of the present study was to determine the acute feeding and
      digestive response of A. purpuratus in relation to short acclimation periods (1,
      3 and 7 days) and exposure to variable salinity (24 per thousand, 27 per thousand
      and 30 per thousand) with two different diets. The feeding behaviour of A.
      purpuratus follows that described for other species of bivalves whereby the
      decrease in salinity produces a reduction in the clearance and ingestion rates.
      This behaviour is not affected by the diet type or the 7 day acclimation period.
      Lower values of absorption efficiency are associated with increasing food
      concentration. The response of the AE at 24 per thousand salinity and low organic
      content diet indicates that the interaction of low salinity and low organic
      content diet reduces the AE to values approaching zero. The enzymatic investment
      of A. purpuratus at low salinity (24 per thousand) is similar for both diets and
      more reduced than for 30 per thousand and 27 per thousand salinity. The results
      show that osmotic stress leads to a reduction of the enzymatic response capacity.
      The multiple regression analysis indicates that different responses are observed
      as a function of the enzymatic activity and the organ. A reduction of the
      carbohydrase activities in the digestive gland was observed to low salinity (24
      per thousand), specifically amylase and celullase. The results of this study are
      ecophysiologically relevant and highlight a relationship between digestive
      enzymatic activity and salinity, and may explain the possible differences in the
      energetic balance of A. purpuratus in response to changes in salinity.

PMID- 15961338
TI  - [Evaluation of post transfusion hypertransaminasemia].
AB  - Dosage of post transfusion ALT has been performed since a government
      recommendation was issued in 1996. Yet, the advantage of this analysis during the
      post transfusion tests has not been determined. The aims of this study were to
      estimate: a) the incidence of hypertransaminasemia, b) the causes of
      hypertransaminasemia and c) the advantage of an etiologic investigation. PATIENTS
      AND METHODS: At the University Hospital of Brest, follow-up of the labile blood
      products recipients was initiated in June 1993. Since 1997, a visit in the
      hepatogastroenterology unit was systematically proposed to patients having post
      transfusion hypertransaminasemia. RESULTS: Since November 1997 to July 2003, ALT
      increase was detected in 235 patients (4%). Among them, 108 patients consulted a
      hepatologist. Diagnosis was certain for 46 patients (46%). A drug reaction or
      alcoholic disease was the cause of ALT elevation in the majority of cases (80%).
      The diagnosis was probable for 42 patients (39%) due to medications in 81% of
      cases. The diagnosis remained undetermined in 20 patients (18%). CONCLUSION: Our
      study shows that alcohol or drug hepatotoxicity explained the majority of post
      transfusion hypertransaminasemia. We could not demonstrate a viral cause. We have
      decided to continue the follow-up of post transfusion hypertransaminasemia during
      two more years and to reevaluate the usefulness of the etiologic investigation.

PMID- 15961339
TI  - Allergen-specific IgE and IgG4 are markers of resistance and susceptibility in a
      human intestinal nematode infection.
AB  - IgG4 has been proposed to act as a 'blocking antibody' due to its ability to
      compete for the same epitopes as IgE thus preventing IgE-dependent allergic
      responses. IgG4 and IgE are both elevated in helminth infections and strong anti
      parasite IgE responses are associated with resistance to infection. We wished to
      determine the relationship between anti-parasite IgG4 and IgE and Ascaris
      lumbricoides infection status. We examined anti-parasite responses, including
      antibody levels to recombinant Ascaris allergen-1A (rABA-1A), a target of serum
      IgE in endemic populations. Worm burden was indirectly estimated by measuring
      parasite egg output in a cross-sectional human population (N = 105). Levels of
      anti-parasite IgG4 and IgE in patients' plasma were quantified by immunoassay.
      Global anti-parasite antibody responses did not bear any significant
      relationships with intensity of Ascaris infection. Individuals who had detectable
      levels of IgE but not IgG4 to rABA-1A (11%) had lower average levels of infection
      compared with individuals who produced anti-rABA-1A IgG4 (40%) and sero-negative
      individuals (49%) (P = 0.008). The ratio of IgG4/IgE in rABA-1A responders
      positively correlated with intensity of infection (P < 0.025). IgG4 levels
      positively correlated with infection level in younger children (age 4-11) where
      average levels of infection were increasing (P = 0.038), whereas allergen
      specific IgE emerged as a correlate of immunity in older children and adults (age
      12-36) where infection levels were decreasing (P = 0.048). Therefore, in a
      gastrointestinal helminth infection, differential regulation of anti-allergen
      antibody isotypes relate to infection level. Our results are consistent with the
      concept that IgG4 antibody can block IgE-mediated immunity and therefore allergic
      processes in humans.

PMID- 15961340
TI  - Genetic fuzzy modelling and control of bispectral index (BIS) for general
      intravenous anaesthesia.
AB  - Based on an adaptive genetic fuzzy clustering algorithm, a derived fuzzy
      knowledge model is proposed for quantitatively estimating the systolic arterial
      pressure (SAP), heart rate (HR), and bispectral index (BIS) using 12 patients and
      it validates them according to pharmacological reasoning. Also, a genetic
      proportional integral derivative controller (GPIDC) to adaptive three controller
      parameters and a genetic fuzzy logic controller (GFLC) to adaptive controller
      rules using genetic algorithms (GAs) were simulated and compared each other in a
      patient model using the BIS value as a controlled variable. Each controller was
      tested using a set of 12 virtual patients undergoing a Gaussian random surgical
      disturbance repeated with BIS targets set at 40, 50, and 60. Controller
      performance was assessed using mean absolute error (MAE) of the BIS target, the
      percentage of time with acceptable BIS control (PTABC), and drug consumption
      (DC). It was found that the MAE value of the BIS target was significantly lower
      (P < 0.05) and the values of PTABC and DC of BIS target were significantly higher
      (P < 0.05) in BIS targets set at 40 than at 50 or 60 in both GPIDC and GFLC.
      However, when compared with two controllers in terms of the values of MAE, PTABC,
      and DC each other in BIS targets set at 40, 50, and 60, there were no significant
      differences (P > 0.05). Furthermore, when the simulation results in these two
      controllers were compared with routine standard practice of 12 clinical trials
      (i.e., manual control) in BIS target set at 50, the values of PTABC in both GPIDC
      and GFLC groups were significantly higher (P < 0.05) than in the manual control
      group. In contrast, there were no significant differences (P > 0.05) for these
      three groups in terms of drug consumption. This indicates that either GPIDC or
      GFLC can control the BIS target set at 50 better than manual control, although
      the similar drug consumption is used.

PMID- 15961341
TI  - Predicting genotoxicity of aromatic and heteroaromatic amines using
      electrotopological state indices.
AB  - A quantitative structure-activity relationship (QSAR) model relating
      electrotopological state (E-state) indices and mutagenic potency was previously
      described by Cash [Mutat. Res. 491 (2001) 31-37] using a data set of 95 aromatic
      amines published by Debnath et al. [Environ. Mol. Mutagen. 19 (1992) 37-52].
      Mutagenic potency was expressed as the number of Salmonella typhimurium TA98
      revertants per nmol (LogR). Earlier work on the development of QSARs for the
      prediction of genotoxicity indicated that numerous methods could be effectively
      employed to model the same aromatic amines data set, namely, Debnath et al.;
      Maran et al. [Quant. Struct.-Act. Relat. 18 (1999) 3-10]; Basak et al. [J. Chem.
      Inf. Comput. Sci. 41 (2001) 671-678]; Gramatica et al. [SAR QSAR Environ. Res. 14
      (2003) 237-250]. However, results obtained from external validations of those
      models revealed that the effective predictivity of the QSARs was well below the
      potential indicated by internal validation statistics (Debnath et al., Gramatica
      et al.). The purpose of the current research is to externally validate the model
      published by Cash using a data set of 29 aromatic amines reported by Glende et
      al. [Mutat. Res. 498 (2001) 19-37; Mutat. Res. 515 (2002) 15-38] and to further
      explore the potential utility of using E-state sums for the prediction of
      mutagenic potency of aromatic amines.

PMID- 15961342
TI  - Infrared and Raman bands of phytantriol as markers of hydrogen bonding and
      interchain interaction.
AB  - Hydrogen bonding and interchain interactions in phytantriol, 3,7,11,15
      tetramethyl-1,2,3-hexadecanetriol, have been studied by Fourier transform
      infrared (FT-IR) and Raman spectroscopies. Assignments of the bands were
      performed based on the OH/OD isotopic substitution, molecular modeling, and
      measurements of polarized Raman spectra. Marker bands were evaluated from the
      temperature-dependent spectral changes. It is shown that Raman spectroscopy
      provides sensitive markers, namely I(delta(CH2))/I(deltas(CH3)), tau(CH)2,
      I(nus(CH3)(FR))/I(nus(CH2)), and nus(CH2) for probing the interactions between
      the hydrocarbon chains. Hydrogen bonding interaction might be studied through the
      difference Raman spectroscopy by the analysis of polarized band at 811 cm-1.
      Relationship is found between the frequencies of IR bands at 883-873 and 1097
      1086 cm-1, associated with the vibrations localized at the primary COH site, and
      the frequencies of OH stretching mode, making these bands specific markers in the
      analysis of hydrogen bonding. Evaluated marker bands may be of utility to probe
      the interchain and hydrogen bonding interaction of phytantriol with guest
      molecules in the practically important aqueous liquid-crystalline phases of this
      lipid.

PMID- 15961343
TI  - The search for new targets for cancer chemotherapeutics.

PMID- 15961345
TI  - Fibulins and cancer: friend or foe?
AB  - The fibulins are a family of secreted glycoproteins, which are characterised by
      repeated epidermal-growth-factor-like domains and a unique C-terminal structure.
      Six distinct fibulin genes, encoding at least nine protein products generated by
      alternative splicing, have been identified. Considerable evidence is available
      pointing towards a structural role for fibulins within the extracellular matrix.
      Fibulins have been shown to modulate cell morphology, growth, adhesion and
      motility. The dysregulation of certain fibulins occurs in a range of human
      disorders, including cancer. Indeed, both tumour suppressive and oncogenic
      activities have been proposed for members of the fibulin family. Herein, we
      discuss the possible roles of fibulins in cancer, in addition to their diagnostic
      and therapeutic potential.

PMID- 15961347
TI  - Dreaming of seizures.
AB  - Could some dreams and temporal lobe seizures share an intrinsic neuronal network?
      At the interplay of emotion, memory, dream, and temporal lobe seizure, we report
      on a patient with a left dysplastic amygdala and temporal lobe epilepsy who
      presented with a typical seizure while dreaming. Neuronal networks subserving
      affective states are suggested to be involved in emotional dream, memory recall,
      and amygdalo-hippocampal seizures.

PMID- 15961346
TI  - Increased expression and release of functional tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) by T cells from lupus patients with active
      disease.
AB  - Increased expression of TRAIL in membrane-bound and soluble form in patients with
      systemic lupus erythematosus (SLE) has been previously reported. In this study,
      we characterized the upregulation of T-cell-associated and soluble TRAIL (sTRAIL)
      in vivo and the modulation of TRAIL expression and soluble protein release in
      vitro following T cell activation and IFNalpha exposure. The expression of
      membrane-bound TRAIL as determined by flow cytometry was higher on CD4(+) and
      CD8(+) T cells from lupus patients compared to controls, particularly on
      activated CD69(+)CD8(+) T cells. Similarly, sTRAIL levels determined by ELISA
      were significantly elevated in serum from patients with active SLE and correlated
      with levels of IFNalpha. In vitro, both T-cell-associated and sTRAIL were
      maximally induced by T cell activation plus IFNalpha in patients and controls. By
      Western blot analysis, sTRAIL was detected in sera in both the monomeric and
      multimeric, functional form. Both forms of TRAIL were functional in vitro as
      determined by Annexin V staining and (51)Cr release assay but the apoptotic
      activity of membrane TRAIL was 2.5-fold higher compared to that of sTRAIL. These
      results indicate that IFNalpha-induced enhancement of TRAIL expression and of
      TRAIL-mediated apoptosis may amplify the abnormal apoptotic process in SLE.

PMID- 15961348
TI  - Stigma and safe havens: a medical sociological perspective on African-American
      female epilepsy patients.
AB  - PURPOSE: Very little is known about the attitudes and behaviors of minorities
      with epilepsy. This pilot study explored access to health care, help-seeking
      behaviors, and adherence to treatment among African-American females with
      epilepsy. METHODS: Ethnographic interviews were conducted with 10 African
      American female adults. RESULTS: Findings indicate four major obstacles to care:
      limited financial resources, lack of knowledge about epilepsy among African
      Americans, poor patient-provider communication, and lack of social support.
      Social support impacted individuals seeking surgery, and also affected purchasing
      medication, adherence to medical treatment, and needed transportation. Lack of
      knowledge and misinformation about epilepsy in the African-American community and
      poor communication with physicians contribute to the social stigma felt by these
      patients. CONCLUSIONS: The behavioral epidemiology of epilepsy among African
      Americans is lacking. This disease exacerbates health disparities for this
      population. These findings point to a need for a safe haven for these
      individuals.

PMID- 15961349
TI  - The h-channel: a potential channelopathy in epilepsy?
AB  - Ion channelopathy is a proven cause of inherited human epilepsy, and may play a
      role in acquired epileptic syndromes as well. Of the many ion channel causes of
      epilepsy, the h-channel is a potential new addition. H-channels are voltage-gated
      ion channels with unique biophysical properties. The h-channel exerts a
      significant modulatory influence on neuronal excitability, and is a target of
      antiepileptic drugs. Further, its activity is influenced by seizures, raising the
      question of whether it may play a role in epileptogenesis as well. This review
      summarizes the evidence for the contribution of h-channels to seizures and
      epilepsy, and outlines hypotheses concerning the existence of an "h
      channelopathy" in human epilepsy.

PMID- 15961350
TI  - Patient and physician reactions to generic antiepileptic substitution in the
      treatment of epilepsy.
AB  - BACKGROUND: The clinical and economic consequences of generic antiepileptic drug
      (AED) substitution are not yet fully understood. This article provides a broad
      perspective of generic AED substitution in five countries. METHODS: Two cross
      sectional telephone-based surveys (patient and physician) were undertaken in
      Canada, the United Kingdom, France, Germany, and Spain. A total of 1409
      interviews, 974 patients and 435 physicians, were completed. RESULTS: Across all
      countries studied, patients and physicians alike have elevated concerns about the
      safety and efficacy of generic AEDs as compared with drugs for acute care.
      CONCLUSION: There is an opposition to generic substitution by both patients and
      physicians, especially with concern over increased breakthrough seizure risk.
      Further evidence is required to understand how costs and effects of generic AED
      substitution affect patient welfare.

PMID- 15961352
TI  - Repair of DNA lesions in chromosomal DNA impact of chromatin structure and
      Cockayne syndrome proteins.
AB  - Decondensation of chromatin is essential to facilitate access to DNA metabolizing
      processes such as transcription and DNA repair. Disruption of histone-DNA
      contacts by histone modification or by ATP dependent chromatin remodelling allows
      DNA-binding proteins to compete with histones for DNA. The efficiency of global
      genome nucleotide excision repair (GGR) that removes a variety of helix
      distorting DNA lesions is known to be affected by chromatin structure most
      notably demonstrated by the slow repair of heterochromatin. In addition, the
      efficiency of GGR to repair lesions in transcriptionally active genes requires
      functional CSA and B proteins. We found that repair of UV-photolesions in both
      strands of the active adenosine deaminase gene was delayed in CS cells when
      compared to normal human fibroblasts. We suggest that the lack of transcription
      recovery characteristic for CS cells exposed to DNA damaging agents, might lead
      to changes in the chromatin structure of active genes, causing less efficient
      repair of lesions in these genes when compared to normal cells.

PMID- 15961351
TI  - Beta-adrenergic receptor regulation of pigment epithelial-derived factor
      expression in rat retina.
AB  - In the present study, we have examined a potential mechanism by which sympathetic
      nerves regulate PEDF and whether its down regulation may be responsible for
      increased capillary density observed after sympathectomy. Six weeks post
      sympathectomy, eyes were removed from female Sprague-Dawley rats for Western blot
      analysis, RNA isolation, real-time PCR, and immunohistochemistry for measurement
      of PEDF expression. The contralateral or left eye was used as an intra-animal
      control. In addition, retinal pigment epithelial cells were grown in culture and
      treated with norepinephrine and propranolol. An ELISA assay was used to determine
      the amount of PEDF secreted into the RPE media. Quantitative results of Western
      blot analysis and real-time PCR confirm that both steady-state gene expression
      and protein levels of PEDF are significantly decreased in the sympathectomized
      retina (P<0.05) when compared to the contralateral retina. Qualitative results of
      immunohistochemistry verify that PEDF is located predominantly in the RPE cell
      layer of the retina, and levels are decreased in the sympathectomized retina.
      ELISA results illustrate that norepinephrine significantly increases PEDF
      secretion by RPE cells and propranolol slightly decreases PEDF secretion into RPE
      cell medium. In conclusion, down regulation of PEDF may contribute to the
      increased capillary density of the outer plexiform layer in the retina noted
      after sympathectomy. Furthermore, expression of PEDF was significantly increased
      after treatment of norepinephrine in RPE medium demonstrating a role of beta
      adrenergic regulation of PEDF. Since sympathetic nerves are damaged in diabetes
      and PEDF appears to be regulated by beta-adrenergic receptors, these results
      suggest a role for sympathetic nerves in diabetic retinopathy. This knowledge, in
      turn, may be used for future treatment and prevention of diabetic retinopathy and
      other ocular diseases.

PMID- 15961353
TI  - Transcription promotes guanine to thymine mutations in the non-transcribed strand
      of an Escherichia coli gene.
AB  - Transcription of DNA opens the chromatin, causes topological changes in DNA and
      transiently exposes the two strands to different biochemical environments.
      Consequently, it has long been argued that transcription may promote damage to
      DNA and there are data in Escherichia coli and yeast supporting a correlation
      between high transcription and mutations. We examined the transcription
      dependence of the reversion of a nonsense codon (TGA) in E. coli and found that
      there was a strong dependence of mutations on transcription in strains defective
      in the repair of 8-oxoguanine in DNA. Under conditions of high transcription
      there was a three to five-fold increase in mutations that changed TGA in the non
      transcribed strand to a sense codon. Furthermore, in both mutY and mutM mutY
      backgrounds the mutations were overwhelmingly G:C to T:A. In contrast, when the
      TGA was in the transcribed strand in relation with the inducible promoter, high
      transcription decreased the rate of reversion. Similar results were obtained in a
      strain defective in the transcription-repair coupling factor, Mfd, suggesting
      that transcription dependent increase in base substitutions does not require
      transcription-dependent DNA repair. However, Mfd does modulate the magnitude of
      the mutagenic effect of transcription. These data are consistent with a model in
      which the non-transcribed strand is more susceptible to oxidative damage during
      transcription than the transcribed strand. These results suggest that the
      magnitudes of individual base substitutions and their relative numbers in other
      studies of mutational spectra may also be affected by transcription.

PMID- 15961354
TI  - Nucleotide excision repair in chromatin and the right of entry.
AB  - DNA is packaged with histones and other accessory proteins into chromatin in
      eukaryotic cells. It is well established that the assembly of DNA into chromatin
      affects induction of DNA damage as well as repair of the damage. How the DNA
      repair machinery detects a lesion and 'fixes it' in chromatin has been an
      intriguing question since the dawn of understanding DNA packaging in chromatin.
      Direct recognition/binding by damaged DNA binding proteins is one obvious tactic
      to detect a lesion. Rearrangement of chromatin structure during DNA repair was
      reported more than two decades ago. This early observation suggests that
      unfolding of chromatin structure may be required to facilitate DNA repair after
      lesions are detected. Cells can also exploit DNA processing events to assist DNA
      repair. Transcription coupled repair (TCR) is such an example. During TCR, an RNA
      polymerase blocked by a lesion, may act as a signal to recruit DNA repair
      machinery. Possible roles of histone modification enzymes, ATP-dependent
      chromatin remodeling complexes and chromatin assembly factors in DNA repair are
      discussed.

PMID- 15961355
TI  - The Drosophila mus 308 gene product, implicated in tolerance of DNA interstrand
      crosslinks, is a nuclear protein found in both ovaries and embryos.
AB  - mus 308 designates one of over 30 mutagen sensitivity loci found in Drosophila.
      It is predicted to code for a 229-kDa polypeptide. Published sequence analyses of
      others indicate that this polypeptide would have helicase motifs near its N
      terminus, and similarities to bacterial DNA polymerase I-like enzymes near its C
      terminus. In our studies, two different and highly specific antibodies were
      prepared and used for identification as well as characterization of the mus 308
      gene product. Western blot analyses reveal a single reactive polypeptide in both
      ovaries and embryos as well as in two Drosophila embryo tissue culture cell
      lines; it is nearly absent in homozygous mus 308 mutants. This polypeptide is
      about 229 kDa in size, and indirect immunofluorescence shows that the mus 308
      gene product localizes throughout nuclei in wild-type cells but appears to be
      absent in a mus 308 mutant. Immunoblot analyses throughout development suggest
      greatest abundance at the end of embryogenesis, immediately before hatching of
      first instar larvae. They also showed a smaller ( approximately 100 kDa)
      antigenically and genetically related polypeptide found only in adult males.
      Immunoprecipitation, a highly effective method of specific purification, suggests
      that the mus 308 protein has DNA polymerase activity that is NEM-sensitive but
      largely aphidicolin-resistant. In addition, the immunoprecipitated material has
      DNA-dependent ATPase but lacks detectable helicase.

PMID- 15961356
TI  - Detection of Pseudomonas aeruginosa in patients with cystic fibrosis.
AB  - Chronic pulmonary colonisation with Pseudomonas aeruginosa (PA) in patients with
      CF is associated with a high morbidity and mortality. Adequate treatment of first
      acquisition of PA might prevent or postpone chronic colonisation. Early detection
      of PA is therefore of major importance. Currently, cultures of oropharynx or
      sputum are most commonly practised. However, oropharyngeal culture has
      limitations both in the positive and negative predictive value for the presence
      of PA in the lower respiratory tract. Induction of sputum has little benefit in
      detection of PA. Serology might have additional value in early detection, when
      bacterial density is too low to be detected by culture. Molecular techniques are
      not yet widespread used for detection of PA, but have in general a high
      sensitivity. In this review, we describe the value of different diagnostic
      techniques for detecting PA.

PMID- 15961357
TI  - Reduction in vertebral fracture risk in teriparatide-treated postmenopausal women
      as assessed by spinal deformity index.
AB  - Teriparatide is the first bone-building drug available for the treatment of
      osteoporosis. We investigated the efficacy of this compound as assessed by spinal
      deformity index (SDI) using data from the Fracture Prevention Trial (FPT). The
      FPT was a randomized, double blind trial of placebo versus teriparatide 20 microg
      (TPTD20) versus teriparatide 40 microg (TPTD40) administered by daily self
      injection. Patients included in the current analyses were those patients from the
      placebo (n = 398) and TPTD20 (the approved dose, n = 403) groups with baseline
      and follow-up radiographs and at least one vertebral fracture at baseline. For
      each vertebra, a visual semiquantitative grade of 0, 1, 2, or 3 was assigned for
      no fracture or mild, moderate, or severe fracture, respectively; the SDI was
      calculated by summing the fracture grades of all T4 to L4 vertebrae. The mean SDI
      increased in the placebo and TPTD20 groups by 0.485 and 0.134, respectively (P <
      0.001). The proportions of patients with SDI increases >1, >2, and >3 were
      reduced by 85%, 80%, and 80%, respectively. In the placebo group, increasing
      baseline SDI was correlated with the mean increase in SDI during the trial (r =
      0.080, P = 0.01), consistent with the progressive natural history of
      osteoporosis. However, in the TPTD20 group, increasing baseline SDI was not
      correlated with the mean increase in SDI during the trial (P = 0.297) indicating
      that teriparatide mitigated or eliminated the increased risk associated with
      increasing fracture burden. Increases in SDI during the trial were associated
      with increasing proportions of patients with new or worsening back pain and
      greater mean height loss (P < 0.0001), demonstrating an association with
      important clinical consequences. The results indicate that teriparatide greatly
      reduced the increase in fracture burden in the FPT and mitigated or eliminated
      the risk for future fractures imparted by increasing baseline fracture burden.

PMID- 15961358
TI  - Regional differences in trabecular BMD and micro-architecture of weight-bearing
      bone under habitual gait loading--a pQCT and microCT study in human cadavers.
AB  - This study used both multi-slice pQCT and microCT to investigate regional changes
      in bone mineral density and structural parameters in the ultradistal tibia and in
      the mid-femoral neck under habitual gait loading. Twenty cadavers with 2 females
      and 18 males aged 70.8 +/- 8.5 were used in this study. Seventy-two cylindrical
      bone cores with 5 mm in diameter and 10 mm in length from the anterior/posterior
      and superior/inferior regions were obtained from ultradistal tibia and mid-femur
      neck, respectively, so that their differences in terms of volumetric trabecular
      bone mineral density (tBMD) as well as micro-architectural parameters could be
      studied. The results showed that the mean volumetric tBMD at both the organ
      (including the bone marrow spaces) and tissue levels (excluding the bone marrow
      spaces) were a 49.2% and 28.3%, respectively, lower in the anterior bone cores
      than in the posterior bone cores from the ultradistal tibia (P < 0.01). MicroCT
      measurements on BV/TV, BS/TV, Tb.N, Tb.Th, and DA were found to be on average of
      33.5%, 23.6%, 9.1%, 18.0%, and 14.6%, respectively, lower in the anterior
      trabecular bone cores (P < 0.001), while Tb.Sp and SMI were 12.5% and 29.3%,
      respectively, higher in the anterior trabecular bone cores (P < 0.01). No
      significant difference in micro-architectural parameters was found in the
      trabecular bone cores obtained from mid-femoral neck, except that the mean DA of
      the inferior bone cores was significantly higher by 30.1% than that of the
      superior bone cores (P = 0.01). A statistically significant linear relationship
      with the correlation coefficient, ranging from 0.37 to 0.94 and -0.62 to -0.85,
      respectively, was shown between the tBMD at the organ level and all of the micro
      architectural parameters (P < 0.05). We suggest that dynamic loading changes
      during the striking of the heel in normal gait, as well as the peaks of the hip
      joint reaction force occur during the heel strike and before toe off positions in
      the lifetime of the subject may account for such regional differences in BMD and
      micro-architecture. The findings from the correlation study also suggest that,
      apart from BMD, the micro-architecture may exhibit adaptation in response to such
      excessive loading.

PMID- 15961359
TI  - Worksite-based parenting programs to promote healthy adolescent sexual
      development: a qualitative study of feasibility and potential content.
AB  - CONTEXT: Parents can play a significant role in promoting healthy sexual
      development and risk reduction among adolescents, but many are uncertain about
      how to talk with their adolescents about sex. Worksites provide an untapped but
      promising setting in which to reach parents to help them develop parenting and
      communication skills. METHODS: Focus groups with 33 employed parents of
      adolescents and 41 high school students, and interviews with seven worksite
      executives, explored the desire for worksite-based parenting programs, how best
      to implement programs and recommendations for content. Standard qualitative
      analysis techniques were used to identify major themes in participants' comments.
      RESULTS: Parents and employers were enthusiastic about worksite-based parenting
      programs. Parents reported that adolescents are reluctant to talk with them, but
      acknowledged their own inexperience talking about sex. Their suggestions included
      that programs be held at lunchtime, give participants opportunities to interact
      with each other and with facilitators, and give participants exercises to
      practice at home. Employers described potential benefits (e.g., improved employee
      morale) and challenges (e.g., privacy concerns) of programs. Teenagers said that
      their parents made false assumptions about their sexual activity if they asked
      about sex. Participants suggested that parenting programs cover adolescent
      development, sex, abstinence and communication (e.g., how to start
      conversations). CONCLUSIONS: A worksite-based program designed to help parents of
      adolescents develop communication and parenting skills could provide a way to
      reach busy parents. Recommendations from parents, employers and teenagers can be
      used to make such a program appealing and effective.

PMID- 15961360
TI  - Availability of services for emergency contraceptive pills at high school-based
      health centers.
AB  - CONTEXT: School-based health centers have the potential to increase adolescents'
      awareness of, access to and use of emergency contraceptive pills, which can
      prevent unintended pregnancy following unprotected sex. METHODS: In 2001, 250
      high school-based health centers responded to a nationwide mail survey that
      assessed the provision of education, referral and prescription services for
      emergency contraceptive pills, as well as the perceived benefits and barriers
      related to offering these services. Frequencies, cross-tabulations and logistic
      regression models were used to analyze the data. RESULTS: Fifty-nine percent of
      the centers provided education and referrals for emergency contraceptive pills,
      while 30% provided prescriptions. Staff generally identified the same benefits of
      and barriers to services, although centers that provided services were more
      likely than nonproviders to report benefits and less likely to report barriers.
      Predictors of offering education were providing reproductive health services
      (odds ratio, 4.6) and citing the increased likelihood that students would use the
      method (3.5) and have the opportunity to discuss contraception (2.6). Reporting
      the benefit of pregnancy prevention was a predictor of offering referrals (2.9),
      while providing reproductive health services (30.4) and citing pregnancy
      prevention (6.3) were predictors of offering prescriptions. Predictors of the
      decreased likelihood of offering services were also identified. CONCLUSIONS:
      School centers that provide all three services have the greatest potential to
      ensure the successful use of emergency contraceptive pills by adolescents. While
      the number of centers offering services appears to be increasing, greater efforts
      are needed to improve students' awareness of and access to the method so they can
      make informed decisions regarding their reproductive health.

PMID- 15961361
TI  - Poor knowledge regarding the Pap test among low-income women undergoing routine
      screening.
AB  - CONTEXT: Many women undergoing cervical cancer screening lack appropriate
      understanding of the Pap test. It is important to evaluate knowledge and
      informational needs about Pap testing among groups who may have difficulty
      accessing care or a relatively low likelihood of obtaining follow-up for an
      abnormal result, such as minority and low-income women. METHODS: A sample of 338
      women undergoing cervical screening at two clinics in Texas completed a
      questionnaire measuring their knowledge of Pap testing and asking what specific
      information they would like to know about the test. Group comparisons and
      qualitative analyses were conducted. RESULTS: Women correctly answered an average
      of 8.7 out of 20 questions; the range was 0-17. Mean scores were higher among
      white women (10.2) than among blacks (8.4) and Hispanics (7.4), among women with
      more than a high school education than among their less educated counterparts
      (10.0 vs. 7.9) and among women with an annual household income of at least
      $10,000 than among those with a lower income (9.3 vs. 8.4). Knowledge scores did
      not differ according to Pap history. Open-ended questioning identified a need for
      information on the purpose of the test, exam procedures, abnormal test results
      and prognosis. CONCLUSIONS: Minority women and those of low socioeconomic status
      had poor understanding of Pap testing. Identifying misunderstandings in this
      vulnerable population and improving patient education on the most basic aspects
      of Pap testing may increase adherence to follow-up when abnormalities are
      detected.

PMID- 15961362
TI  - Evaluation of a peer provider reproductive health service model for adolescents.
AB  - CONTEXT: The use of peer providers in family planning clinics has been proposed
      as a strategy that could better serve sexually active adolescent populations.
      METHODS: Baseline and follow-up survey data from 1,424 female and 166 male
      adolescent clients of five California community health clinics were analyzed to
      assess the effectiveness of a peer provider model between 1996 and 1999.
      Multivariable analyses examined differences in outcomes between clients' first
      and last clinic visits, and by whether clients received only clinical services or
      other components of the model (outreach and telephone follow-up) as well.
      RESULTS: Female clients were significantly more likely at their last visit than
      at their first visit to report consistent birth control use (odds ratio, 1.9),
      use at last intercourse (1.8) and use of effective methods (3.5), and were
      significantly less likely to report consistent condom use (0.7). There were no
      significant differences in male birth control or condom use between first and
      last visits. Females who received all components of the model were more likely
      than those who received only clinical services to return for an annual exam (2.2)
      and to make three or more visits during the study period (1.7). The full model
      was particularly effective for females who were Hispanic, had been born to
      adolescent mothers or had had more than one sexual partner in the six months
      before their first clinic visit. CONCLUSIONS: The peer provider model appears to
      be a promising addition to the mix of service delivery models, particularly for
      certain subgroups of clients. The findings underscore the importance of tailoring
      programs on the basis of clients' risk profiles.

PMID- 15961363
TI  - Advanced practice clinicians' interest in providing medical abortion: results of
      a California survey.
AB  - CONTEXT: California's Reproductive Health Privacy Act, which became law in
      January 2003, clarified that advanced practice clinicians could legally provide
      medical abortion. Little is known about the characteristics associated with
      nonphysician clinicians' interest in receiving medical abortion training or their
      perceptions of barriers to medical abortion provision. METHODS: In early 2003, a
      total of 1,176 licensed advanced practice clinicians in California-nurse
      practitioners, physician assistants and certified nurse-midwives-completed a mail
      in survey assessing their personal characteristics, beliefs and clinical
      practices. Weighted univariate and bivariate analyses were conducted to describe
      the respondents, their interest in receiving medical abortion training and their
      perceptions of barriers to providing such care. RESULTS: One-quarter of
      respondents desired training in medical abortion. A higher proportion of nurse
      midwives than of nurse practitioners or physician assistants desired training
      (42% vs. 24% and 23%, respectively). The proportion of respondents desiring
      training also was elevated among clinicians who have prochoice attitudes, those
      who are familiar with medical abortion and those who spend at least one-third of
      their time providing care to women of reproductive age. Lack of training
      opportunities, legal uncertainties and clinical facility constraints were the
      most frequently reported perceived barriers to provision of medical abortion.
      CONCLUSIONS: Considerable proportions of advanced practice clinicians-especially
      of nurse-midwives-may be interested in receiving medical abortion training.
      Perceived barriers to providing medical abortion are amenable to change. Policies
      and programs are needed to ensure that interested, committed clinicians can
      overcome barriers to providing medical abortion for their patients.

PMID- 15961364
TI  - From Peter, Jane and Tiptoes to literacy as freedom.

PMID- 15961365
TI  - Evaluation of a developmental care training programme for neonatal nurses.
AB  - Although the impact of developmental care on premature infants has been
      investigated at length, often the issue of professional development and training
      related to this type of care has not been examined. The aim of the present study
      was to evaluate the impact of a developmental care training programme on nurses'
      behaviours and cognitive attributes with regard to the prevention of
      overstimulation of premature infants. The Theory of Reasoned Action (TRA) was the
      framework underlying the study. This programme evaluation used a quasi
      experimental one group pre-test/post-test design. Participants were nurses
      working in a neonatal intensive care unit. Data were collected by self
      administered questionnaires. Significantly higher post-test scores were observed
      for knowledge and for a variety of theoretical constructs. The results of this
      study showed the potential of such training programmes to help nurses implement
      developmental care.

PMID- 15961366
TI  - Survey of medication administration policies within schools in Sheffield.
AB  - National guidelines exist to help schools in supporting pupils with medical
      needs. However, school staff are not contractually bound to help with the
      administration of medication and policies differ across schools, depending on
      local needs and views. A postal survey was conducted in Sheffield to elicit
      schools' views regarding medication administration. Over 80 percent of the
      responding schools were willing to administer long-term medication and 67 percent
      would help with short-term needs as well. Written information from professionals
      is valued by most schools and many would prefer that dosages of medication are
      adjusted to avoid school hours. Of the schools, 17 percent did not want to take
      any responsibility for medication administration. Reluctance seems to arise from
      perceived lack of training and fear of litigation. These issues need to be
      addressed in order to improve school staff's confidence with the administration
      of medication.

PMID- 15961367
TI  - Emotional reactions of parents after the birth of an infant with extremely low
      birth weight.
AB  - Emotional reactions of parents after the birth of an extremely low birth weight
      (ELBW) infant were followed during the early period of hospital care. Ten pairs
      of parents participated. The process concerning feelings of sadness, anger,
      fear/anxiety and joy was measured by Single Systems Design (SSD). The infants
      were born in gestation weeks 23-27. The emotional reactions of the mothers and
      fathers did not differ significantly. There was emotional confusion during the
      first weeks of parenthood, then the negative feelings decreased and joy
      increased. But at the end of a long period of care, the negative feelings
      reappeared. It is important to be aware that the first weeks after birth can be
      marked by emotional confusion and that negative feelings can return when the
      infant's medical status has been brought under control. The latter might be
      explained emotionally as a delayed crisis reaction.

PMID- 15961368
TI  - Consulting on feeding and sleeping problems in child health care: what is at the
      bottom of advice to parents?
AB  - The aim of this study was to investigate and interpret ideas inherent in sleep
      and diet consultations concerning infants in Swedish child health services. Data
      were obtained through semi-structured interviews of professionals employed in
      these services. A qualitative method with a phenomenological approach was applied
      to analyse the data. The results indicate that professionals have underlying
      conceptions. They considered that when parents force food on their child, this is
      a violation of the child's integrity. This view is based on the idea that such
      actions restrict the child's right to self-determination. In the participants'
      opinions, when the child is forced to sleep well, this is not regarded as a
      violation of the child's integrity, but is perceived as support of the child's
      autonomy. An underlying theoretical view may be that parents' time can be saved
      if the child becomes independent of the parents at as early an age as possible.

PMID- 15961369
TI  - The experience of being ill as narrated by hospitalized children aged 7-10 years
      with short-term illness.
AB  - Children's illness has been investigated through the eyes of parents and nurses
      but the child's own perspective has been largely ignored. The aim of this study
      is to illuminate the 7-10-year-olds' experiences of being ill. Three girls and
      four boys were interviewed and narrated their experience about short-term
      illness. The data obtained was subjected to a thematic qualitative content
      analysis. The analysis suggests that the children combined reality and
      imagination and contrasts seemed to coexist such as being scared/confident,
      sad/cosy and hurt/having fun. They felt caught and tried to escape. The
      experience of illness as narrated by children can lead to a richer understanding
      and influence the way we care for paediatric patients.

PMID- 15961371
TI  - Dynamic myocardial contractile parameters from left ventricular pressure-volume
      measurements.
AB  - A new dynamic model of left ventricular (LV) pressure-volume relationships in
      beating heart was developed by mathematically linking chamber pressure-volume
      dynamics with cardiac muscle force-length dynamics. The dynamic LV model
      accounted for >80% of the measured variation in pressure caused by small
      amplitude volume perturbation in an otherwise isovolumically beating, isolated
      rat heart. The dynamic LV model produced good fits to pressure responses to
      volume perturbations, but there existed some systematic features in the residual
      errors of the fits. The issue was whether these residual errors would be damaging
      to an application where the dynamic LV model was used with LV pressure and volume
      measurements to estimate myocardial contractile parameters. Good agreement among
      myocardial parameters responsible for response magnitude was found between those
      derived by geometric transformations of parameters of the dynamic LV model
      estimated in beating heart and those found by direct measurement in constantly
      activated, isolated muscle fibers. Good agreement was also found among myocardial
      kinetic parameters estimated in each of the two preparations. Thus the small
      systematic residual errors from fitting the LV model to the dynamic pressure
      volume measurements do not interfere with use of the dynamic LV model to estimate
      contractile parameters of myocardium. Dynamic contractile behavior of cardiac
      muscle can now be obtained from a beating heart by judicious application of the
      dynamic LV model to information-rich pressure and volume signals. This provides
      for the first time a bridge between the dynamics of cardiac muscle function and
      the dynamics of heart function and allows a beating heart to be used in studies
      where the relevance of myofilament contractile behavior to cardiovascular system
      function may be investigated.

PMID- 15961372
TI  - TTX-sensitive voltage-gated Na+ channels are expressed in mesenteric artery
      smooth muscle cells.
AB  - The presence and properties of voltage-gated Na+ channels in mesenteric artery
      smooth muscle cells (SMCs) were studied using whole cell patch-clamp recording.
      SMCs from mouse and rat mesenteric arteries were enzymatically dissociated using
      two dissociation protocols with different enzyme combinations. Na+ and Ca2+
      channel currents were present in myocytes isolated with collagenase and elastase.
      In contrast, Na+ currents were not detected, but Ca2+ currents were present in
      cells isolated with papain and collagenase. Ca2+ currents were blocked by
      nifedipine. The Na+ current was insensitive to nifedipine, sensitive to changes
      in the extracellular Na+ concentration, and blocked by tetrodotoxin with an IC50
      at 4.3 nM. The Na+ conductance was half maximally activated at -16 mV, and steady
      state inactivation was half-maximal at -53 mV. These values are similar to those
      reported in various SMC types. In the presence of 1 microM batrachotoxin, the Na+
      conductance-voltage relationship was shifted by 27 mV in the hyperpolarizing
      direction, inactivation was almost completely eliminated, and the deactivation
      rate was decreased. The present study indicates that TTX-sensitive, voltage-gated
      Na+ channels are present in SMCs from the rat and mouse mesenteric artery. The
      presence of these channels in freshly isolated SMC depends critically on the
      enzymatic dissociation conditions. This could resolve controversy about the
      presence of Na+ channels in arterial smooth muscle.

PMID- 15961373
TI  - Relief from a heavy heart: redox-sensitive NF-kappaB as a therapeutic target in
      managing cardiac hypertrophy.

PMID- 15961374
TI  - Myocardial postconditioning: reperfusion injury revisited.

PMID- 15961375
TI  - Mitochondrial permeability transition pore as a target for cardioprotection in
      the human heart.
AB  - After an episode of myocardial ischemia, opening of the mitochondrial
      permeability transition pore (mPTP), at the onset of reperfusion, is a critical
      determinant of myocyte death. We investigated the role of the mPTP as a target
      for cardioprotection in the human heart. We subjected human atrial tissue,
      harvested from patients undergoing cardiac surgery, to a period of lethal hypoxia
      and investigated the effect of suppressing mPTP opening at the onset of
      reoxygenation. We found that suppressing mPTP opening at the onset of
      reoxygenation with known mPTP inhibitors cyclosporin A (CsA, 0.2 micromol/l) and
      sanglifehrin A (SfA, 1.0 micromol/l) 1) improved recovery of baseline contractile
      function from 29.4 +/- 2.0% under control conditions to 48.7 +/- 2.2% with CsA
      and 46.1 +/- 2.3% with SfA (P < 0.01) and 2) improved cell survival from 62.8 +/-
      5.3% under hypoxic control conditions to 91.4 +/- 4.1% with CsA and 87.2 +/- 6.2%
      with SfA (P < 0.001). Furthermore, with a cell model in which oxidative stress
      was used to induce mPTP opening in human atrial myocytes, we demonstrated
      directly that CsA and SfA mediated their cardioprotective effects by inhibiting
      mPTP opening, as evidenced by an extension in the time required to induce mPTP
      opening from 116 +/- 8 s under control conditions to 189 +/- 10 s with CsA and
      183 +/- 12 s with SfA (P < 0.01). We report that suppressing mPTP opening at the
      onset of reoxygenation protects human myocardium against lethal hypoxia
      reoxygenation injury. This suggests that, in the human heart, the mPTP is a
      viable target for cardioprotection.

PMID- 15961376
TI  - Assembly, activation, and signaling by kinin-forming proteins on human vascular
      smooth muscle cells.
AB  - Cardiovascular disease is the number one cause of death in the United States.
      Vascular smooth muscle cells (VSMC) are an important constituent of the vessel
      wall that can bring about pathological changes leading to vascular disease.
      Depending on the environment, the function of VSMC can deviate profoundly from
      its normal contractile role. Despite advances in research, the underlying
      mechanisms that activate VSMC toward vascular disease are poorly understood. For
      the first time, we have observed that factor XII and high-molecular-weight
      kininogen, constituents of the blood plasma, can bind to VSMC in a Zn2+-dependent
      manner. In the presence of prekallikrein, this assembly of factor XII and high
      molecular-weight kininogen on VSMC leads to the activation of prekallikrein to
      kallikrein with a rapid formation of bradykinin. The amount of bradykinin in the
      culture medium then decreases, presumably because of the presence of a kininase
      activity. p44/42 mitogen-activated protein kinase is rapidly phosphorylated in
      response to in situ-generated or in vitro-added bradykinin and is inhibited by
      bradykinin antagonist HOE-140. Binding of factor XII to VSMC also results in a
      concentration-dependent phosphorylation of p44/42 mitogen-activated protein
      kinase. This early mitogenic signal, which is also implicated in atherogenesis,
      may change the metabolic and proliferative activity of VSMC, which are key steps
      in the progression of atherosclerosis.

PMID- 15961377
TI  - Paradoxical attenuation of leukocyte rolling in response to ischemia- reperfusion
      and extracorporeal blood circulation in inflamed tissue.
AB  - In contrast to acute preparations such as the exteriorized mesentery or the
      cremaster muscle, chronically instrumented chamber models allow one to study the
      microcirculation under "physiological" conditions, i.e., in the absence of trauma
      induced leukocyte rolling along the venular endothelium. To underscore the
      importance of studying the naive microcirculation, we implanted titanium dorsal
      skinfold chambers in hamsters and used intravital fluorescence microscopy to
      study venular leukocyte rolling in response to ischemia-reperfusion injury or
      extracorporeal blood circulation. The experiments were performed in chambers that
      fulfilled all well-established criteria for a physiological microcirculation as
      well as in chambers that showed various extents of leukocyte rolling due to
      trauma, hemorrhage, or inflammation. In ideal chambers with a physiological
      microcirculation (<30 rolling leukocytes/mm vessel circumference in 30 s),
      ischemia-reperfusion injury and extracorporeal blood circulation significantly
      stimulated leukocyte rolling along the venular endothelium and, subsequently,
      firm leukocyte adhesion. In contrast, both stimuli failed to elicit leukocyte
      rolling in borderline chambers (30-100 leukocytes/mm), and in blatantly inflamed
      chambers with yet higher numbers of rolling leukocytes at baseline (>100
      leukocytes/mm), we observed a paradoxical reduction of leukocyte rolling after
      ischemia-reperfusion injury or extracorporeal blood circulation. A similar effect
      was observed when we superfused leukotriene B4 (LTB4) onto the chamber tissue.
      The initial increase in leukocyte rolling in response to an LTB4 challenge was
      reversed by a second superfusion 90 min later. These observations underscore 1)
      the benefit of studying leukocyte-endothelial cell interaction in chronically
      instrumented chamber models and 2) the necessity to strictly adhere to well
      established criteria of a physiological microcirculation.

PMID- 15961378
TI  - Bax translocates from cytosol to mitochondria in cardiac cells during apoptosis:
      development of a GFP-Bax-stable H9c2 cell line for apoptosis analysis.
AB  - The proapoptotic protein Bax plays an important role in cardiomyocytic cell
      death. Ablation of this protein has been shown to diminish cardiac damage in Bax
      knockout mice during ischemia-reperfusion. Presently, studies of Bax-mediated
      cardiac cell death examined primarily the expression levels of Bax and its
      prosurvival factor Bcl-2 rather than the localization of this protein, which
      dictates its function. Using immunofluorescence labeling, we have shown that in
      neonatal rat cardiomyocytes and in H9c2 cardiomyoblasts, Bax translocates from
      cytosol to mitochondria upon the induction of apoptosis by hypoxia-reoxygenation
      serum withdrawal and by the presence of the free-radical inducer menadione. Also,
      we found that Bax translocation to mitochondria was associated with the exposure
      of an NH2-terminal epitope, and that this translocation could be partially
      blocked by the prosurvival factors Bcl-2 and Bcl-XL. To visualize the
      translocation of Bax in living cells, we have developed an H9c2 cell line that
      stably expresses green fluorescent protein (GFP)-tagged Bax. This cell line has
      GFP-Bax localized primarily in the cytosol in the absence of apoptotic inducers.
      Upon induction of apoptosis by a number of stimuli, including menadione,
      staurosporine, sodium nitroprusside, and hypoxia-reoxygenation-serum withdrawal,
      we could observe the translocation of Bax from cytosol to mitochondria. This
      translocation was not affected by retinoic acid-induced differentiation of H9c2
      cells. Additionally, this translocation was associated with loss of mitochondrial
      membrane potential, release of cytochrome c, and fragmentation of nuclei.
      Finally, using a tetramethylrhodamine-based dye, we have shown that a rapid
      screening process based on the loss of mitochondrial membrane potential could be
      developed to monitor GFP-Bax translocation to mitochondria. Overall, the GFP-Bax
      stable H9c2 cell line that we have developed represents a unique tool for
      examining Bax-mediated apoptosis, and it could be of great importance in
      screening therapeutic compounds that could block Bax translocation to
      mitochondria to attenuate apoptosis.

PMID- 15961379
TI  - Does load-induced ventricular hypertrophy progress to systolic heart failure?
AB  - Ventricular hypertrophy develops in response to numerous forms of cardiac stress,
      including pressure or volume overload, loss of contractile mass from prior
      infarction, neuroendocrine activation, and mutations in genes encoding sarcomeric
      proteins. Hypertrophic growth is believed to have a compensatory role that
      diminishes wall stress and oxygen consumption, but Framingham and other studies
      established ventricular hypertrophy as a marker for increased risk of developing
      chronic heart failure, suggesting that hypertrophy may have maladaptive features.
      However, the relative contribution of comorbid disease to hypertrophy-associated
      systolic failure is unknown. For instance, coronary artery disease is induced by
      many of the same risk factors that cause hypertrophy and can itself lead to
      systolic dysfunction. It is uncertain, therefore, whether ventricular hypertrophy
      commonly progresses to systolic dysfunction without the contribution of
      intervening ischemia or infarction. In this review, we summarize findings from
      epidemiologic studies, preclinical experiments in animals, and clinical trials to
      lay out what is known-and not known-about this important question.

PMID- 15961380
TI  - Differentially expressed proteins in the pancreas of diet-induced diabetic mice.
AB  - The pancreas is a heterogeneous organ mixed with both exocrine and endocrine
      cells. The pancreas is involved in metabolic activities with the endocrine cells
      participating in the regulation of blood glucose, while the exocrine portion
      provides a compatible environment for the pancreatic islets and is responsible
      for secretion of digestive enzymes. The purpose of this study was to identify
      pancreatic proteins that are differentially expressed in normal mice and those
      with diet-induced type 2 diabetes (T2DM). In this study, C57BL/6J male mice fed a
      high fat diet became obese and developed T2DM. The pancreatic protein profiles
      were compared between control and diabetic mice using two-dimensional gel
      electrophoresis. Differentially expressed protein "spots" were identified by mass
      spectrometry. REG1 and REG2 proteins, which may be involved in the proliferation
      of pancreatic beta cells, were up-regulated very early in the progression of
      obese mice to T2DM. Glutathione peroxidase, which functions in the clearance of
      reactive oxidative species, was found to be down-regulated in the diabetic mice
      at later stages. The RNA levels encoding REG2 and glutathione peroxidase were
      compared by Northern blot analysis and were consistent to the changes in protein
      levels between diabetic and control mice. The up-regulation of REG1 and REG2
      suggests the effort of the pancreas in trying to ameliorate the hyperglycemic
      condition by stimulating the proliferation of pancreatic beta cells and enhancing
      the subsequent insulin secretion. The down-regulation of glutathione peroxidase
      in pancreas could contribute to the progressive deterioration of beta cell
      function due to the hyperglycemia-induced oxidative stress.

PMID- 15961381
TI  - Expression clustering reveals detailed co-expression patterns of functionally
      related proteins during B cell differentiation: a proteomic study using a
      combination of one-dimensional gel electrophoresis, LC-MS/MS, and stable isotope
      labeling by amino acids in cell culture (SILAC).
AB  - B cells play an essential role in the immune response. Upon activation they may
      differentiate into plasma cells that secrete specific antibodies against
      potentially pathogenic non-self antigens. To identify the cellular proteins that
      are important for efficient production of these antibodies we set out to study
      the B cell differentiation process at the proteome level. We performed an in
      depth proteomic study to quantify dynamic relative protein expression patterns of
      several hundreds of proteins at five consecutive time points after
      lipopolysaccharide-induced activation of B lymphocytes. The proteome analysis was
      performed using a combination of stable isotope labeling using [13C6]leucine
      added to the murine B cell cultures, one-dimensional gel electrophoresis, and LC
      MS/MS. In this study we identified 1,001 B cell proteins. We were able to
      quantify the expression levels of a quarter of all identified proteins (i.e. 234)
      at each of the five different time points. Nearly all proteins revealed changes
      in expression patterns. The quantitative dataset was further analyzed using an
      unbiased clustering method. Based on their expression profiles, we grouped the
      entire set of 234 quantified proteins into a limited number of 12 distinct
      clusters. Functionally related proteins showed a strong correlation in their
      temporal expression profiles. The quality of the quantitative data allowed us to
      even identify subclusters within functionally related classes of proteins such as
      in the endoplasmic reticulum proteins that are involved in antibody production.

PMID- 15961382
TI  - Heteromeric protein complexes mediate zinc transport into the secretory pathway
      of eukaryotic cells.
AB  - The cation diffusion facilitator (CDF) family of metal ion transporters plays
      important roles in zinc transport at all phylogenetic levels. In this report, we
      describe a novel interaction between two members of the CDF family in
      Saccharomyces cerevisiae. One CDF member in yeast, Msc2p, was shown recently to
      be involved in zinc transport into the endoplasmic reticulum (ER) and required
      for ER function. We describe here a newly recognized CDF family member in yeast,
      Zrg17p. ZRG17 was previously identified as a zinc-regulated gene controlled by
      the zinc-responsive Zap1p transcription factor. A zrg17 mutant exhibits the same
      zinc-suppressible phenotypes as an msc2 mutant, including an induction of the
      unfolded protein response in low zinc. Moreover, a significant fraction of the
      total Zrg17p protein appears to localize to the ER. Their common phenotypes and
      localization suggested that these two proteins function together to mediate zinc
      transport into the ER. Consistent with this hypothesis, Msc2p and Zrg17p
      physically interact with each other, as determined by co-immunoprecipitation.
      Therefore, we propose that Msc2p and Zrg17p form a heteromeric zinc transport
      complex in the ER membrane. We also demonstrate that ZnT5 and ZnT6, mammalian
      homologues of Msc2p and Zrg17p, functionally interact as well. These results
      suggest that heteromeric complexes formed by different CDF members may be a
      common phenomenon for this ubiquitous family of metal ion transporters.

PMID- 15961383
TI  - Energetic mapping of transition state analogue interactions with human and
      Plasmodium falciparum purine nucleoside phosphorylases.
AB  - Human purine nucleoside phosphorylase (huPNP) is essential for human T-cell
      division by removing deoxyguanosine and preventing dGTP imbalance. Plasmodium
      falciparum expresses a distinct PNP (PfPNP) with a unique substrate specificity
      that includes 5'-methylthioinosine. The PfPNP functions both in purine salvage
      and in recycling purine groups from the polyamine synthetic pathway. Immucillin-H
      is an inhibitor of both huPNP and PfPNPs. It kills activated human T-cells and
      induces purine-less death in P. falciparum. Immucillin-H is a transition state
      analogue designed to mimic the early transition state of bovine PNP. The DADMe
      Immucillins are second generation transition state analogues designed to match
      the fully dissociated transition states of huPNP and PfPNP. Immucillins, DADMe
      Immucillins and related analogues are compared for their energetic interactions
      with human and P. falciparum PNPs. Immucillin-H and DADMe-Immucillin-H are 860
      and 500 pM inhibitors against P. falciparum PNP but bind human PNP 15-35 times
      more tightly. This common pattern is a result of kcat for huPNP being 18-fold
      greater than kcat for PfPNP. This energetic binding difference between huPNP and
      PfPNP supports the k(chem)/kcat binding argument for transition state analogues.
      Preferential PfPNP inhibition is gained in the Immucillins by 5'-methylthio
      substitution which exploits the unique substrate specificity of PfPNP. Human PNP
      achieves part of its catalytic potential from 5'-OH neighboring group
      participation. When PfPNP acts on 5'-methylthioinosine, this interaction is not
      possible. Compensation for the 5'-OH effect in the P. falciparum enzyme is
      provided by improved leaving group interactions with Asp206 as a general acid
      compared with Asn at this position in huPNP. Specific atomic modifications in the
      transition state analogues cause disproportionate binding differences between
      huPNP and PfPNPs and pinpoint energetic binding differences despite similar
      transition states.

PMID- 15961384
TI  - The nipah virus fusion protein is cleaved within the endosomal compartment.
AB  - Nipah virus (NiV) is a recently emerged and highly pathogenic paramyxovirus that
      causes a systemic infection in animals and humans and can infect a wide range of
      cultured cells. Interestingly, the NiV fusion (F) protein has a single arginine
      at the cleavage site similar to paramyxoviruses that are activated by exogenous
      trypsin-like enzymes only present in specific cells and tissues and therefore
      only cause localized infections. We show here that NiV F activation is not
      mediated by an exogenous serum protease but by an endogenous ubiquitous cellular
      protease after endocytosis of the protein. In addition to endocytosis,
      acidification of the endosome is a prerequisite for F cleavage. These results
      show that activation of the NiV F protein depends on a type of proteolytic
      cleavage that is clearly different from what is known for other paramyxoviral and
      orthomyxoviral fusion proteins. To our knowledge, this is the first example of a
      viral class I fusion protein whose activation depends on clathrin-mediated
      constitutive endocytosis.

PMID- 15961385
TI  - Organic cation permeation through the channel formed by polycystin-2.
AB  - Polycystin-2 (PC2), a member of the transient receptor potential family of ion
      channels (TRPP2), forms a calcium-permeable cation channel. Mutations in PC2 lead
      to polycystic kidney disease. From the primary sequence and by analogy with other
      channels in this family, PC2 is modeled to have six transmembrane domains.
      However, most of the structural features of PC2, such as how large the channel is
      and how many subunits make up the pore of the channel, are unknown. In this
      study, we estimated the pore size of PC2 from the permeation properties of the
      channel. Organic cations of increasing size were used as current carriers through
      the PC2 channel after PC2 was incorporated into lipid bilayers. We found that
      dimethylamine, triethylamine, tetraethylammonium, tetrabutylammonium,
      tetrapropylammonium, and tetrapentylammonium were permeable through the PC2
      channel. The slope conductance of the PC2 channel decreased as the ionic diameter
      of the organic cation increased. For each organic cation tested, the currents
      were inhibited by gadolinium and anti-PC2 antibody. Using the dimensions of the
      largest permeant cation, the minimum pore diameter of the PC2 channel was
      estimated to be at least 11 A. The large pore size suggests that the primary
      state of this channel found in vivo is closed to avoid rundown of cation
      gradients across the plasma membrane and excessive calcium leak from endoplasmic
      reticulum stores.

PMID- 15961387
TI  - Unloading induces osteoblastic cell suppression and osteoclastic cell activation
      to lead to bone loss via sympathetic nervous system.
AB  - Osteoporosis is one of the major health problems in our modern world. Especially,
      disuse (unloading) osteoporosis occurs commonly in bedridden patients, a
      population that is rapidly increasing due to aging-associated diseases. However,
      the mechanisms underlying such unloading-induced pathological bone loss have not
      yet been fully understood. Since sympathetic nervous system could control bone
      mass, we examined whether unloading-induced bone loss is controlled by
      sympathetic nervous tone. Treatment with beta-blocker, propranolol, suppressed
      the unloading-induced reduction in bone mass. Conversely, beta-agonist,
      isoproterenol, reduced bone mass in loaded mice, and under such conditions,
      unloading no longer further reduced bone mass. Analyses on the cellular bases
      indicated that unloading-induced reduction in the levels of osteoblastic cell
      activities, including mineral apposition rate, mineralizing surface, and bone
      formation rate, was suppressed by propranolol treatment and that isoproterenol
      induced reduction in these levels of bone formation parameters was no longer
      suppressed by unloading. Unloading-induced reduction in the levels of mineralized
      nodule formation in bone marrow cell cultures was suppressed by propranolol
      treatment in vivo. In addition, loss of a half-dosage in the dopamine beta
      hydroxylase gene suppressed the unloading-induced bone loss and reduction in
      mineralized nodule formation. Unloading-induced increase in the levels of
      osteoclastic activities such as osteoclast number and surface as well as urinary
      deoxypyridinoline was all suppressed by the treatment with propranolol. These
      observations indicated that sympathetic nervous tone mediates unloading-induced
      bone loss through suppression of bone formation by osteoblasts and enhancement of
      resorption by osteoclasts.

PMID- 15961386
TI  - Plant gamma-glutamyl hydrolases and folate polyglutamates: characterization,
      compartmentation, and co-occurrence in vacuoles.
AB  - gamma-Glutamyl hydrolase (GGH, EC 3.4.19.9) catalyzes removal of the polyglutamyl
      tail from folyl and p-aminobenzoyl polyglutamates. Plants typically have one or a
      few GGH genes; Arabidopsis has three, tandemly arranged on chromosome 1, which
      encode proteins with predicted secretory pathway signal peptides. Two
      representative Arabidopsis GGH proteins, AtGGH1 and AtGGH2 (the At1g78660 and
      At1g78680 gene products, respectively) were expressed in truncated form in
      Escherichia coli and purified. Both enzymes were active as dimers, had low K(m)
      values (0.5-2 microm) for folyl and p-aminobenzoyl pentaglutamates, and acted as
      endopeptidases. However, despite 80% sequence identity, they differed in that
      AtGGH1 cleaved pentaglutamates, mainly to di- and triglutamates, whereas AtGGH2
      yielded mainly monoglutamates. Analysis of subcellular fractions of pea leaves
      and red beet roots established that GGH activity is confined to the vacuole and
      that this activity, if not so sequestered, would deglutamylate all cellular
      folylpolyglutamates within minutes. Purified pea leaf vacuoles contained an
      average of 20% of the total cellular folate compared with approximately 50 and
      approximately 10%, respectively, in mitochondria and chloroplasts. The main
      vacuolar folate was 5-methyltetrahydrofolate, of which 51% was polyglutamylated.
      In contrast, the principal mitochondrial and chloroplastic forms were 5-formyl-
      and 5,10-methenyltetrahydrofolate polyglutamates, respectively. In beet roots, 16
      60% of the folate was vacuolar and was again mainly 5-methyltetrahydrofolate, of
      which 76% was polyglutamylated. These data point to a hitherto unsuspected role
      for vacuoles in folate storage. Furthermore, the paradoxical co-occurrence of GGH
      and folylpolyglutamates in vacuoles implies that the polyglutamates are somehow
      protected from GGH attack.

PMID- 15961388
TI  - Identification of TopBP1 as a c-Abl-interacting protein and a repressor for c-Abl
      expression.
AB  - Expression of BCR-ABL is the leading cause of chronic myelogenous leukemia. In
      chronic myelogenous leukemia cells, c-Abl expression is silenced by promoter
      methylation. In addition, the level of c-Abl needs to be tightly and constantly
      regulated due to its cytotoxicity and its rapid degradation after activation. Yet
      the regulation of c-Abl expression remains unclear. In an effort to gain better
      understanding of c-Abl function, we performed a glutathione S-transferase-Abl
      pull-down screen and identified TopBP1, a topoisomerase IIbeta-binding protein
      that contains Brca1 C-terminal motifs and has been implicated in DNA damage
      response. Their physical interaction was verified by in vitro and in vivo assays
      with TopBP1 found as a substrate of Abl proteins. TopBP1 could repress the
      expression of c-Abl at both mRNA and protein levels. Reporter assays indicate
      that TopBP1 directly repressed the promoter activity of c-Abl. Furthermore,
      TopBP1 repressed expression of c-Abl through a novel mechanism that involved
      histone deacetylation and DNA methylation. This transcriptional repression was
      inhibited by c-Abl in a kinase-dependent manner. The dual antagonistic interplay
      between c-Abl and TopBP1 may also provide a mechanism for fine-tuning of c-Abl
      levels.

PMID- 15961389
TI  - G-protein-coupled receptor signaling components localize in both sarcolemmal and
      intracellular caveolin-3-associated microdomains in adult cardiac myocytes.
AB  - This study tests the hypothesis that G-protein-coupled receptor (GPCR) signaling
      components involved in the regulation of adenylyl cyclase (AC) localize with
      caveolin (Cav), a protein marker for caveolae, in both cell-surface and
      intracellular membrane regions. Using sucrose density fractionation of adult
      cardiac myocytes, we detected Cav-3 in both buoyant membrane fractions (BF) and
      heavy/non-buoyant fractions (HF); beta2-adrenergic receptors (AR) in BF; and
      AC5/6, beta1-AR, M4-muscarinic acetylcholine receptors (mAChR), mu-opioid
      receptors, and Galpha(s) in both BF and HF. In contrast, M2-mAChR, Galpha(i3),
      and Galpha(i2) were found only in HF. Immunofluorescence microscopy showed co
      localization of Cav-3 with AC5/6, Galpha(s), beta2-AR, and mu-opioid receptors in
      both sarcolemmal and intracellular membranes, whereas M2-mAChR were detected only
      intracellularly. Immunofluorescence of adult heart revealed a distribution of Cav
      3 identical to that in isolated adult cardiac myocytes. Upon immunoelectron
      microscopy, Cav-3 co-localized with AC5/6 and Galpha(s) in sarcolemmal and
      intracellular vesicles, the latter closely allied with T-tubules. Cav-3
      immunoprecipitates possessed components that were necessary and sufficient for
      GPCR agonist-promoted stimulation and inhibition of cAMP formation. The
      distribution of GPCR, G-proteins, and AC with Cav-3 in both sarcolemmal and
      intracellular T-tubule-associated regions indicates the existence of multiple Cav
      3-localized cellular microdomains for signaling by hormones and drugs in the
      heart.

PMID- 15961390
TI  - TrkA induces apoptosis of neuroblastoma cells and does so via a p53-dependent
      mechanism.
AB  - Neuroblastoma (NB) is the most frequent solid extracranial tumor in children. Its
      clinical prognosis correlates with the expression of members of the Trk
      neurotrophin receptor family, which includes TrkA and TrkB. TrkA expression is
      associated with favorable prognosis, whereas TrkB expression is associated with
      poor prognosis. Here we show that TrkA expression induces the apoptosis of NB
      cells and does so by modulating the levels or activities of a number of proteins
      involved in regulating cell survival and apoptosis, including p53, Bcl-2, and
      caspase-3. TrkA increased the expression of p53 target proteins and failed to
      induce apoptosis in cells where p53 was inactivated by mutation or via expression
      of dominant inhibitory p53 or E1B55K, indicating that TrkA mediates apoptosis, at
      least in part, through p53. Treatment with a caspase inhibitor or overexpression
      of Bcl-X(L) also prevented TrkA from inducing apoptosis. In contrast, elevated
      expression of TrkA in non-transformed sympathetic neurons resulted in the
      suppression of p53 levels and enhanced survival. These results identify apoptosis
      as a novel biological response of TrkA in NB cells and imply that TrkA is a good
      prognosis marker for NB due in part to its ability to mediate apoptosis when
      expressed at sufficient levels.

PMID- 15961391
TI  - Recoverin undergoes light-dependent intracellular translocation in rod
      photoreceptors.
AB  - Photoreceptor cells have a remarkable capacity to adapt the sensitivity and speed
      of their responses to ever changing conditions of ambient illumination. Recent
      studies have revealed that a major contributor to this adaptation is the
      phenomenon of light-driven translocation of key signaling proteins into and out
      of the photoreceptor outer segment, the cellular compartment where
      phototransduction takes place. So far, only two such proteins, transducin and
      arrestin, have been established to be involved in this mechanism. To investigate
      the extent of this phenomenon we examined additional photoreceptor proteins that
      might undergo light-driven translocation, focusing on three Ca(2+)-binding
      proteins, recoverin and guanylate cyclase activating proteins 1 (GCAP1) and
      GCAP2. The changes in the subcellular distribution of each protein were assessed
      quantitatively using a recently developed technique combining serial tangential
      sectioning of mouse retinas with Western blot analysis of the proteins in the
      individual sections. Our major finding is that light causes a significant
      reduction of recoverin in rod outer segments, accompanied by its redistribution
      toward rod synaptic terminals. In both cases the majority of recoverin was found
      in rod inner segments, with approximately 12% present in the outer segments in
      the dark and less than 2% remaining in that compartment in the light. We suggest
      that recoverin translocation is adaptive because it may reduce the inhibitory
      constraint that recoverin imposes on rhodopsin kinase, an enzyme responsible for
      quenching the photo-excited rhodopsin during the photoresponse. To the contrary,
      no translocation of rhodopsin kinase itself or either GCAP was identified.

PMID- 15961392
TI  - Checkpoint kinase 1 regulates diallyl trisulfide-induced mitotic arrest in human
      prostate cancer cells.
AB  - We have shown previously that diallyl trisulfide (DATS), a constituent of
      processed garlic, inhibits proliferation of PC-3 and DU145 human prostate cancer
      cells by causing G(2)-M phase cell cycle arrest in association with inhibition of
      cyclin-dependent kinase 1 activity and hyperphosphorylation of Cdc25C at
      Ser(216). Here, we report that DATS-treated PC-3 and DU145 cells are also
      arrested in mitosis as judged by microscopy following staining with anti-alpha
      tubulin antibody and 4',6-diamidino-2-phenylindole and flow cytometric analysis
      of Ser(10) phosphorylation of histone H3. The DATS treatment caused activation of
      checkpoint kinase 1 and checkpoint kinase 2, which are intermediaries of DNA
      damage checkpoints and implicated in Ser(216) phosphorylation of Cdc25C. The
      diallyl trisulfide-induced Ser(216) phosphorylation of Cdc25C as well as mitotic
      arrest were significantly attenuated by knockdown of check-point kinase 1 protein
      in both PC-3 and DU145 cells. On the other hand, depletion of checkpoint kinase 2
      protein did not have any appreciable effect on G(2) or M phase arrest or Cdc25C
      phosphorylation caused by diallyl trisulfide. The lack of a role of checkpoint
      kinase 2 in diallyl trisulfide-induced phosphorylation of Cdc25C or G(2)-M phase
      cell cycle arrest was confirmed using HCT-15 cells stably transfected with
      phosphorylation-deficient mutant (T68A mutant) of checkpoint kinase 2. In
      conclusion, the results of the present study suggest existence of a checkpoint
      kinase 1-dependent mechanism for diallyl trisulfide-induced mitotic arrest in
      human prostate cancer cells.

PMID- 15961393
TI  - Tyrosine phosphorylation regulates the proteolytic activation of protein kinase
      Cdelta in dopaminergic neuronal cells.
AB  - Oxidative stress is a key apoptotic stimulus in neuronal cell death and has been
      implicated in the pathogenesis of many neurodegenerative disorders, including
      Parkinson disease (PD). Recently, we demonstrated that protein kinase C-delta
      (PKCdelta) is an oxidative stress-sensitive kinase that can be activated by
      caspase-3-dependent proteolytic cleavage to induce apoptotic cell death in cell
      culture models of Parkinson disease (Kaul, S., Kanthasamy, A., Kitazawa, M.,
      Anantharam, V., and Kanthasamy, A. G. (2003) Eur. J. Neurosci. 18, 1387-1401 and
      Kanthasamy, A. G., Kitazawa, M., Kanthasamy, A., and Anantharam, V. (2003)
      Antioxid. Redox. Signal. 5, 609-620). Here we showed that the phosphorylation of
      a tyrosine residue in PKCdelta can regulate the proteolytic activation of the
      kinase during oxidative stress, which consequently influences the apoptotic cell
      death in dopaminergic neuronal cells. Exposure of a mesencephalic dopaminergic
      neuronal cell line (N27 cells) to H(2)O(2)(0-300 microm) induced a dose-dependent
      increase in cytotoxicity, caspase-3 activation and PKCdelta cleavage. H(2)O(2)
      induced proteolytic activation of PKC was delta mediated by the activation of
      caspase-3. Most interestingly, both the general Src tyrosine kinase inhibitor
      genistein (25 microm) and the p60(Src) tyrosine-specific kinase inhibitor (TSKI;
      5 microm) dramatically inhibited H(2)O(2) and the Parkinsonian toxin 1-methyl-4
      phenylpyridinium-induced PKCdelta cleavage, kinase activation, and apoptotic cell
      death. H(2)O(2) treatment also increased phosphorylation of PKCdelta at tyrosine
      site 311, which was effectively blocked by co-treatment with TSKI. Furthermore,
      N27 cells overexpressing a PKCdelta(Y311F) mutant protein exhibited resistance to
      H(2)O(2)-induced PKCdelta cleavage, caspase activation, and apoptosis. To our
      knowledge, these data demonstrate for the first time that phosphorylation of Tyr
      311 on PKCdelta can regulate the proteolytic activation and proapoptotic function
      of the kinase in dopaminergic neuronal cells.

PMID- 15961394
TI  - Cell adhesion status-dependent histone acetylation is regulated through
      intracellular contractility-related signaling activities.
AB  - Although histone acetylation is important for epigenetic gene transcription,
      histone acetylation regulation by extracellular cues has rarely been evidenced.
      Here, we examined whether and how histone acetylation is regulated by cell
      adhesion-mediated signaling. Gastric carcinoma cells in suspension showed a
      higher histone acetylation, compared with fibronectin-adherent cells. This
      difference was supported by a decreased histone deacetylases activity.
      Furthermore, trichostatin A (TSA)-mediated histone acetylation was significantly
      increased only in suspended, but not in fibronectin-adherent, cells.
      Pharmacological inhibition of intracellular contractility-related myosin light
      chain kinase or RhoA-kinase (ROCK) or expression of ROCK1 small interfering RNA,
      dominant negative RhoA, or active Rac1 decreased basal and TSA-mediated histone
      H3 acetylations in suspended cells,whereas inhibition of calmodulin-dependent
      protein kinase II or transient overexpression of wild type myosin light chain
      kinase enhanced the acetylations. Meanwhile, chromatin immunoprecipitation showed
      higher basal and TSA-enhanced associations of ROCK1 promoter regions with Lys(9)
      acetylated histone 3 in suspended cells than in fibronectin-adherent cells and
      expression of ROCK1 was higher and further increased by TSA treatment in
      suspension. In addition, phosphorylation of myosin light chain was further
      increased by TSA in suspension and higher in anchorage-independent cells over
      adherently growing cells, indicating an inverse relationship between ROCK1
      expression-mediated contractility and cell adhesion abilities. Cell adhesion
      analysis showed that pharmacological activation of intracellular contractility
      related signaling activities decreased cell adhesion abilities, whereas
      inhibition of them increased the adhesion. Taken together, these observations
      suggest that cell adhesion-related signal transduction regulates histone
      acetylation, presumably through a close functional linkage between intracellular
      contractility and histone deacetylases activity/histone acetylation.

PMID- 15961395
TI  - c-Jun/activator protein-1 mediates interleukin-1beta-induced dedifferentiation
      but not cyclooxygenase-2 expression in articular chondrocytes.
AB  - Interleukin (IL)-1beta is a major catabolic pro-inflammatory cytokine involved in
      cartilage destruction-associated processes, such as loss of the differentiated
      chondrocyte phenotype (dedifferentiation) and inflammation. Here, we investigated
      the role of c-Jun and activator protein-1 (AP-1) in IL-1beta-induced
      dedifferentiation and cyclooxygenase (COX)-2 expression in primary cultured
      chondrocytes. IL-1beta induced expression and transient phosphorylation of c-Jun
      in primary cultured chondrocytes. Ectopic expression of c-Jun was sufficient to
      cause dedifferentiation, whereas expression of dominant negative c-Jun blocked IL
      1beta-induced dedifferentiation. Interestingly, modulation of c-Jun expression
      did not affect IL-1beta-induced COX-2 expression. Further experiments revealed
      that c-Jun phosphorylation was mediated by c-Jun N-terminal kinase and was
      required for IL-1beta-induced dedifferentiation but not COX-2 expression.
      Consistent with its ability to induce phosphorylation of c-Jun, IL-1beta caused
      transient activation of AP-1, which is necessary for IL-1beta-induced
      dedifferentiation. IL-1beta treatment suppressed expression of Sox-9, a major
      transcription factor that regulates type II collagen expression. Inhibition of c
      Jun N-terminal kinase or AP-1 reversed IL-1beta-induced suppression of Sox-9, and
      ectopic expression of c-Jun was sufficient to cause suppression of Sox-9. Our
      results collectively suggest that IL-1beta suppresses type II collagen expression
      in articular chondrocytes by inducing expression and phosphorylation of c-Jun, AP
      1 activation, and subsequent suppression of Sox-9.

PMID- 15961396
TI  - Peptidoglycan N-acetylglucosamine deacetylases from Bacillus cereus, highly
      conserved proteins in Bacillus anthracis.
AB  - The genomes of Bacillus cereus and its closest relative Bacillus anthracis
      contain 10 polysaccharide deacetylase homologues. Six of these homologues have
      been proposed to be peptidoglycan N-acetylglucosamine deacetylases. Two of these
      genes, namely bc1960 and bc3618, have been cloned and expressed in Escherichia
      coli, and the recombinant enzymes have been purified to homogeneity and further
      characterized. Both enzymes were effective in deacetylating cell wall
      peptidoglycan from the Gram(+) Bacillus cereus and Bacillus subtilis and the
      Gram(-) Helicobacter pylori as well as soluble chitin substrates and N
      acetylchitooligomers. However, the enzymes were not active on acetylated xylan.
      These results provide insight into the substrate specificity of carbohydrate
      esterase family 4 enzymes. It was revealed that both enzymes deacetylated only
      the GlcNAc residue of the synthetic muropeptide N-acetyl-D-glucosamine-(beta-1,4)
      N-acetylmuramyl-L-alanine-D-isoglutamine. Analysis of the constituent
      muropeptides of peptidoglycan from B. subtilis and H. pylori resulting from
      incubation of the enzymes BC1960 and BC3618 with these polymers and subsequent
      hydrolysis by Cellosyl and mutanolysin, respectively, similarly revealed that
      both enzymes deacetylate GlcNAc residues of peptidoglycan. Kinetic analysis
      toward GlcNAc(2-6) revealed that GlcNAc4 was the favorable substrate for both
      enzymes. Identification of the sequence of N-acetychitooligosaccharides (GlcNAc(2
      4)) following enzymatic deacetylation by using 1H NMR revealed that both enzymes
      deacetylate all GlcNAc residues of the oligomers except the reducing end ones.
      Enzymatic deacetylation of chemically acetylated vegetative peptidoglycan from B.
      cereus by BC1960 and BC3618 resulted in increased resistance to lysozyme
      digestion. This is the first biochemical study of bacterial peptidoglycan N
      acetylglucosamine deacetylases.

PMID- 15961397
TI  - Forkhead transcription factors inhibit vascular smooth muscle cell proliferation
      and neointimal hyperplasia.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration contribute
      significantly to atherosclerosis, postangioplasty restenosis, and transplant
      vasculopathy. Forkhead transcription factors belonging to the FoxO subfamily have
      been shown to inhibit growth and cell cycle progression in a variety of cell
      types. We hypothesized that forkhead proteins may play a role in VSMC biology.
      Under in vitro conditions, platelet-derived growth factor (PDGF)-BB, tumor
      necrosis factor-alpha, and insulin-like growth factor 1 stimulated
      phosphorylation of FoxO in human coronary artery smooth muscle cells via MEK1/2
      and/or phosphatidylinositol 3-kinase-dependent signaling pathways. PDGF-BB, tumor
      necrosis factor-alpha, and insulin-like growth factor 1 treatment resulted in the
      nuclear exclusion of FoxO, whereas PDGF-BB alone down-regulated the FoxO target
      gene, p27(kip1), and enhanced cell survival and progression through the cell
      cycle. These effects were abrogated by overexpression of a constitutively active,
      phosphorylation-resistant mutant of the FoxO family member, TM-FKHRL1. The anti
      proliferative effect of TM-FKHRL1 was partially reversed by small interfering RNA
      against p27(kip1). In a rat balloon carotid arterial injury model, adenovirus
      mediated gene transfer of FKHRL1 caused an increase in the expression of
      p27(kip1) in the VSMC and inhibition of neointimal hyperplasia. These data
      suggest that FoxO activity inhibits VSMC proliferation and activation and that
      this signaling axis may represent a therapeutic target in vasculopathic disease
      states.

PMID- 15961398
TI  - Mutations in human cardiac troponin I that are associated with restrictive
      cardiomyopathy affect basal ATPase activity and the calcium sensitivity of force
      development.
AB  - Human cardiac Troponin I (cTnI) is the first sarcomeric protein for which
      mutations have been associated with restrictive cardiomyopathy. To determine
      whether five mutations in cTnI (L144Q, R145W, A171T, K178E, and R192H) associated
      with restrictive cardiomyopathy were distinguishable from hypertrophic
      cardiomyopathy-causing mutations in cTnI, actomyosin ATPase activity and skinned
      fiber studies were carried out. All five mutations investigated showed an
      increase in the Ca2+ sensitivity of force development compared with wild-type
      cTnI. The two mutations with the worst clinical phenotype (K178E and R192H) both
      showed large increases in Ca2+ sensitivity (deltapCa50 = 0.47 and 0.36,
      respectively). Although at least one of these mutations is not in the known
      inhibitory regions of cTnI, all of the mutations investigated caused a decrease
      in the ability of cTnI to inhibit actomyosin ATPase activity. Mixtures of wild
      type and mutant cTnI showed that cTnI mutants could be classified into three
      different groups: dominant (L144Q, A171T and R192H), equivalent (K178E), or
      weaker (R145W) than wild-type cTnI in actomyosin ATPase assays in the absence of
      Ca2+. Although most of the mutants were able to activate actomyosin ATPase
      similarly to wild-type cTnI, L144Q had significantly lower maximal ATPase
      activities than any of the other mutants or wild-type cTnI. Three mutants (L144Q,
      R145W, and K178E) were unable to fully relax contraction in the absence of Ca2+.
      The inability of the five cTnI mutations investigated to fully inhibit ATPase
      activity/force development and the generally larger increases in Ca2+ sensitivity
      than observed for most hypertrophic cardiomyopathy mutations would likely lead to
      severe diastolic dysfunction and may be the major physiological factors
      responsible for causing the restrictive cardiomyopathy phenotype in some of the
      genetically affected individuals.

PMID- 15961399
TI  - Myosin X is a high duty ratio motor.
AB  - Myosin X is expressed in a variety of cell types and plays a role in cargo
      movement and filopodia extension, but its mechanoenzymatic characteristics are
      not fully understood. Here we analyzed the kinetic mechanism of the ATP
      hydrolysis cycle of acto-myosin X using a single-headed construct (M10IQ1).
      Myosin X was unique for the weak "strong actin binding state" (AMD) with a K(d)
      of 1.6 microm attributed to the large dissociation rate constant (2.1 s(-1)).
      V(max) and K(ATPase) of the actin-activated ATPase activity of M10IQ1 were 13.5
      s(-1) and 17.4 mum, respectively. The ATP hydrolysis rate (>100 s(-1)) and the
      phosphate release rate from acto-myosin X (>100 s(-1)) were much faster than the
      entire ATPase cycle rate and, thus, not rate-limiting. The ADP off-rate from acto
      myosin X was 23 s(-1), which was two times larger than the V(max). The P(i)-burst
      size was low (0.46 mol/mol), indicating that the equilibrium is significantly
      shifted toward the prehydrolysis intermediate. The steady-state ATPase rate can
      be explained by a combination of the unfavorable equilibrium constant of the
      hydrolysis step and the relatively slow ADP off-rate. The duty ratio calculated
      from our kinetic model, 0.6, was consistent with the duty ratio, 0.7, obtained
      from comparison of K(m ATPase) and K(m motility). Our results suggest that myosin
      X is a high duty ratio motor.

PMID- 15961400
TI  - An intramolecular interaction between SH2-kinase linker and kinase domain is
      essential for the catalytic activity of protein-tyrosine kinase-6.
AB  - Protein-tyrosine kinase-6 (PTK6, also known as Brk) is a non-receptor tyrosine
      kinase that contains SH3, SH2, and catalytic (Kinase) domains. We have identified
      an intramolecular interaction between the linker (Linker) region connecting the
      SH2 and Kinase domains and the Kinase domain. Residue Trp-184 within the Linker
      region is essential for the Linker-Kinase interaction but not for the Linker-SH3
      interaction. A recombinant PTK6 Kinase domain connected to the Linker region had
      catalytic activity in terms of autophosphorylation, phosphorylation of a PTK6
      substrate, BKS, and phosphorylation of an oligopeptide substrate, whereas the
      Kinase domain itself, or one connected to a Linker region containing a W184A
      substitution, did not. The introduction of the W184A mutation into PTK6 also
      abrogated autophosphorylation and phosphorylation of another PTK6 substrate,
      Sam68, as well as phosphorylation of intracellular proteins. It also abolished
      the ability of PTK6 to promote proliferation and prevent apoptosis of HEK 293
      cells, as well as to permit anchorage-independent colony formation. Therefore,
      unlike Src family members, in which the Linker-Kinase interaction inhibits
      catalytic activity, in PTK6 this interaction has an essential positive role.

PMID- 15961401
TI  - Architecture of the human ndc80-hec1 complex, a critical constituent of the outer
      kinetochore.
AB  - The Ndc80 complex is a constituent of the outer plate of the kinetochore and
      plays a critical role in establishing the stable kinetochore-microtubule
      interactions required for chromosome segregation in mitosis. The Ndc80 complex is
      evolutionarily conserved and contains the four subunits Spc24, Spc25, Nuf2, and
      Ndc80 (whose human homologue is called Hec1). All four subunits are predicted to
      contain globular domains and extensive coiled coil regions. To gain an insight
      into the organization of the human Ndc80 complex, we reconstituted it using
      recombinant methods. The hydrodynamic properties of the recombinant Ndc80 complex
      are identical to those of the endogenous HeLa cell complex and are consistent
      with a 1:1:1:1 stoichiometry of the four subunits and a very elongated shape. Two
      tight Hec1-Nuf2 and Spc24-Spc25 subcomplexes, each stabilized by a parallel
      heterodimeric coiled coil, maintain this organization. These subcomplexes
      tetramerize via an interaction of the C- and N-terminal portions of the Hec1-Nuf2
      and Spc24-Spc25 coiled coils, respectively. The recombinant complex displays
      normal kinetochore localization upon injection in HeLa cells and is therefore a
      faithful copy of the endogenous Ndc80 complex.

PMID- 15961402
TI  - The retinal G protein-coupled receptor (RGR) enhances isomerohydrolase activity
      independent of light.
AB  - Rod and cone visual pigments use 11-cis-retinal, a vitamin A derivative, as their
      chromophore. Light isomerizes 11-cis- into all-trans-retinal, triggering a
      conformational transition of the opsin molecule that initiates phototransduction.
      After bleaching all-trans-retinal leaves the opsin, and light sensitivity must be
      restored by regeneration of 11-cis-retinal. Under bright light conditions the
      retinal G protein-coupled receptor (RGR) was reported to support this
      regeneration by acting as a photoisomerase in a proposed photic visual cycle. We
      analyzed the contribution of RGR to rhodopsin regeneration under different light
      regimes and show that regeneration, during light exposure and in darkness, is
      slowed about 3-fold in Rgr(-/-) mice. These findings are not in line with the
      proposed function of RGR as a photoisomerase. Instead, RGR, independent of light,
      accelerates the conversion of retinyl esters to 11-cis-retinal by positively
      modulating isomerohydrolase activity, a key step in the "classical" visual cycle.
      Furthermore, we find that light accelerates rhodopsin regeneration, independent
      of RGR.

PMID- 15961403
TI  - Androgen receptor gene knockout male mice exhibit impaired cardiac growth and
      exacerbation of angiotensin II-induced cardiac fibrosis.
AB  - Androgen has anabolic effects on cardiac myocytes and has been shown to enhance
      left ventricular enlargement and function. However, the physiological and patho
      physiological roles of androgen in cardiac growth and cardiac stress-induced
      remodeling remains unclear. We aimed to clarify whether the androgen-nuclear
      androgen receptor (AR) system contributes to the cardiac growth and angiotensin
      II (Ang II)-stimulated cardiac remodeling by using systemic AR-null male mice. AR
      knock-out (ARKO) male mice, at 25 weeks of age, and age-matched wild-type (WT)
      male mice were treated with or without Ang II stimulation (2.0 mg/kg/day) for 2
      weeks. ARKO mice with or without Ang II stimulation showed a significant
      reduction in the heart-to-body weight ratio compared with those of WT mice. In
      addition, echocardiographic analysis demonstrated impairments of both the
      concentric hypertrophic response and left ventricular function in Ang II
      stimulated ARKO mice. Western blot analysis of the myocardium revealed that
      activation of extracellular signal-regulated kinases (ERK) 1/2 and ERK5 by Ang II
      stimulation were lower in ARKO mice than those of WT mice. Ang II stimulation
      caused more prominent cardiac fibrosis in ARKO mice than in WT mice with enhanced
      expression of types I and III collagen and transforming growth factor-beta1 genes
      and with increased Smad2 activation. These results suggest that, in male mice,
      the androgen-AR system participates in normal cardiac growth and modulates
      cardiac adaptive hypertrophy and fibrosis during the process of cardiac
      remodeling under hypertrophic stress.

PMID- 15961404
TI  - Identification of the cyclic-nucleotide-binding domain as a conserved determinant
      of ion-channel cell-surface localization.
AB  - Mutations of a putative cyclic-nucleotide-binding domain (CNBD) can disrupt the
      function of the hyperpolarization-activated cyclic-nucleotide-gated channel
      (HCN2) and the human ether-a-go-go-related gene potassium channel (HERG). Loss of
      function caused by C-terminal truncation, which includes all or part of the CNBD
      in HCN and HERG, has been related to abnormal channel trafficking. Similar
      defects have been reported for several of the missense mutations of HERG
      associated with long QT syndrome type 2 (LQT2). Thus, we postulate that normal
      processing of these channels depends upon the presence of the CNBD. Here, we show
      that removal of the entire CNBD prevents Golgi transit, surface localization and
      function of HERG channel tetramers. This is also true when any of the structural
      motifs of the CNBD is deleted, suggesting that deletion of any highly conserved
      region along the entire length of the CNBD can disrupt channel trafficking.
      Furthermore, we demonstrate that defective trafficking is a consequence of all
      LQT2 mutations in the CNBD, including two mutations not previously assessed and
      two others for which there are conflicting results in the literature. The
      trafficking sensitivity of the CNBD might be of general significance for other
      ion channels because complete deletion of the CNBD or mutations at highly
      conserved residues within the CNBD of the related ERG3 channel and HCN2 also
      prevent Golgi transit. These results broadly implicate the CNBD in ion-channel
      trafficking that accounts for the commonly observed loss of function associated
      with CNBD mutants and provides a rationale for distinct genetic disorders.

PMID- 15961405
TI  - Formin-induced actin cables are required for polarized recruitment of the Ste5
      scaffold and high level activation of MAPK Fus3.
AB  - Little is known about how a mitogen-activated protein kinase (MAPK) cascade is
      targeted to specific sites at the plasma membrane during receptor stimulation. In
      budding yeast, the Ste5 scaffold is recruited to a receptor-coupled G protein
      during mating pheromone stimulation, allowing the tethered MAPK cascade to be
      activated by Ste20, a Cdc42-anchored kinase. Here we show that stable recruitment
      of Ste5 at cortical sites requires the formin Bni1, Bni1-induced actin cables,
      Rho1 and Myo2. Rho1 directs recruitment of Bni1 via the Rho-binding domain, and
      Bni1 mediates localization of Ste5 through actin cables and Myo2, which co
      immunoprecipitates with Ste5 during receptor stimulation. Bni1 is also required
      for polarized recruitment and full activation of MAPK Fus3, which must bind Ste5
      to be activated, and polarized recruitment of Cdc24, the guanine exchange factor
      that binds Ste5 and promotes its recruitment to the G protein. In contrast, Bni1
      is not important for activation of MAPK Kss1, which can be activated while not
      bound to Ste5 and does not accumulate at cortical sites. These findings reveal
      that Bni1 mediates the formation of a Ste5 scaffold/Fus3 MAPK signaling complex
      at polarized sites, and suggests that a pool of Ste5 may translocate along formin
      induced actin cables to the cell cortex.

PMID- 15961406
TI  - Colocalization of muscleblind with RNA foci is separable from mis-regulation of
      alternative splicing in myotonic dystrophy.
AB  - Myotonic dystrophy type I (DM1), which is caused by a non-coding CTG-repeat
      expansion in the dystrophia myotonica-protein kinase (DMPK) gene, is an RNA
      mediated disease. Expanded CUG repeats in transcripts of mutant DMPK form nuclear
      foci that recruit muscleblind-like (MBNL) proteins, a family of alternative
      splicing factors. Although transcripts of mutant DMPK and MBNL proteins
      accumulate in nuclear RNA foci, it is not clear whether foci formation is
      required for splicing mis-regulation. Here, we use a co-transfection strategy to
      show that both CUG and CAG repeats form RNA foci that colocalize with green
      fluorescent protein (GFP)-MBNL1 and endogenous MBNL1. However, only CUG repeats
      alter splicing of the two tested pre-mRNAs, cardiac troponin T (cTNT) and insulin
      receptor (IR). Using FRAP, we demonstrate that GFP-MBNL1 in CUG and CAG foci have
      similar half-times of recovery and fractions of immobile molecules, suggesting
      that GFP-MBNL1 is bound by both CUG and CAG repeats. We also find an immobile
      fraction of GFP-MBNL1 in DM1 fibroblasts and a similar rapid exchange in
      endogenous CUG RNA foci. Therefore, formation of RNA foci and disruption of MBNL1
      regulated splicing are separable events.

PMID- 15961407
TI  - First experiments of selected area nano-diffraction from semiconductor interfaces
      using a spherical aberration corrected TEM.
AB  - Selected area diffraction (SAD) from localized areas that are approximately 20 nm
      in diameter has been demonstrated for the first time using a spherical-aberration
      corrected transmission electron microscope (Cs-corrected TEM). We have succeeded
      in obtaining sharp diffraction patterns from well-defined areas on both sides of
      the interface between a Ti-Si-Ge alloy and Si0.54Ge0.46. The errors in the area
      selection by an SAD aperture are reduced to <2 nm by the Cs-correction. The
      applications of this technique in studies of nanometer-sized materials are
      discussed.

PMID- 15961408
TI  - Adiponectin and high-density lipoprotein: a metabolic association through thick
      and thin.

PMID- 15961409
TI  - Elevated C-reactive protein levels and coronary microvascular dysfunction in
      patients with coronary artery disease.
AB  - AIMS: It is still unknown whether elevated C-reactive protein levels are
      responsible for coronary microcirculatory dysfunction in patients with coronary
      artery disease (CAD). This study was aimed at evaluating the association between
      C-reactive protein levels and endothelium-dependent and endothelium-independent
      coronary blood flow (CBF) responses in non-culprit arteries of patients with CAD.
      METHODS AND RESULTS: We studied 28 patients (14 with normal and 14 with elevated
      C-reactive protein levels, >5 mg/L) with single-vessel disease and otherwise
      angiographically normal coronary arteries undergoing percutaneous transluminal
      coronary angioplasty (PTCA). CBF was measured in the non-PTCA vessel using an
      intracoronary Doppler guide wire and quantitative coronary angiography at
      baseline, after intracoronary infusion of substance P and of adenosine, and
      expressed as per cent change from baseline. The increases in CBF during infusion
      of substance P and of adenosine were lesser in patients with elevated than in
      those with normal C-reactive protein levels (34+/-22 vs. 61+/-34%, P=0.04 and
      131+/-53 vs. 189+/-89%, P=0.03, respectively). Multivariable analysis identified
      elevated C-reactive protein level as the only independent predictor of reduced
      response to substance P (P=0.01) and adenosine (P=0.02). CONCLUSION: In patients
      with CAD, evidence of systemic inflammation is independently associated with
      endothelium-dependent and endothelium-independent coronary microvascular
      dysfunction, which, in turn, may be critical to precipitate myocardial ischaemia,
      in particular, in unstable patients.

PMID- 15961410
TI  - Four-day urocortin-I administration has sustained beneficial haemodynamic,
      hormonal, and renal effects in experimental heart failure.
AB  - AIMS: To investigate the subacute effects of a sustained intravenous infusion of
      urocortin-I (Ucn-I) in experimental heart failure (HF). METHODS AND RESULTS: In
      eight sheep with pacing-induced HF, a 4-day infusion of Ucn-I (0.3 microg/kg/h)
      induced prompt (30 min) and sustained (4-day) increases in cardiac output (CO,
      Day 4: 1.8+/-0.2 vs. 2.3+/-0.2 L/min, P<0.001) and stroke volume (7.8+/-0.8 vs.
      10.2+/-1.0 mL/beat, P=0.0011), and reductions in mean arterial pressure (MAP,
      72+/-3 vs. 70+/-3 mmHg, P=0.0305), left atrial pressure (26+/-1 vs. 11+/-2 mmHg,
      P<0.001), and total calculated peripheral resistance (43+/-6 vs. 32+/-4
      mmHg/L/min, P<0.001). Ucn-I also induced persistent falls in plasma renin (1.34+/
      0.23 vs. 0.77+/-0.10 nmol/L/min, P=0.048), aldosterone (3273+/-1172 vs. 382+/-44
      pmol/L, P=0.0098), endothelin-1 (4.6+/-0.3 vs. 2.7+/-0.3 pmol/L, P<0.001),
      vasopressin (24+/-4 vs. 14+/-2 pmol/L, P=0.0028) and atrial (184+/-14 vs. 154+/
      29 pmol/L, P=0.0226) and brain (43+/-5 vs. 32+/-6 pmol/L, P=0.0016) natriuretic
      peptides. Plasma adrenocorticotrophic hormone and cortisol rose transiently on
      Day 0. Ucn-I enhanced urinary sodium excretion (5.3-fold, P=0.0001) and
      creatinine clearance (1.3-fold, P=0.0055) long-term, and tended to increase urine
      output (P=0.0748). Food intake was attenuated over the first 2 days of treatment
      (P=0.0283). CONCLUSION: Four-day administration of Ucn-I induces sustained
      reductions in cardiac preload and MAP, improvements in CO and renal function, and
      inhibition of a range of vasoconstrictor/volume-retaining factors. These findings
      support Ucn-I's therapeutic potential in HF.

PMID- 15961411
TI  - Calpain 3 participates in sarcomere remodeling by acting upstream of the
      ubiquitin-proteasome pathway.
AB  - Mutations in the non-lysosomal cysteine protease calpain 3 cause limb-girdle
      muscular dystrophy type 2A (LGMD2A). Our previous studies of the calpain 3
      knockout mouse (C3KO) suggested a role for calpain 3 in sarcomere formation and
      remodeling. Calpain 3 may mediate remodeling by cleavage and release of
      myofibrillar proteins, targeting them for ubiquitination and proteasomal
      degradation. Loss of proper protein turnover may be the basis for this muscle
      disease. To test this hypothesis in vivo, we used an experimental model of
      hindlimb unloading and reloading that has been shown to induce sarcomere
      remodeling. We showed that the rate of atrophy and especially the rate of growth
      are decreased in C3KO muscles under conditions promoting sarcomere remodeling. In
      wild-type mice, an elevated level of ubiquitinated proteins was observed during
      muscle reloading, which is presumably necessary to remove atrophy-specific and
      damaged proteins. This increase in ubiquitination correlated with an increase in
      calpain 3 expression. C3KO muscles did not show any increase in ubiquitination at
      the reloading stage, suggesting that calpain 3 is necessary for ubiquitination
      and that it acts upstream of the ubiquitination machinery. We found upregulation
      of heat shock proteins in C3KO muscles following challenge with a physiological
      condition that requires highly increased protein degradation. Furthermore, old
      C3KO mice show evidence of insoluble protein aggregate formation in skeletal
      muscles. These studies suggest that accumulation of aged and damaged proteins can
      lead to cellular toxicity and a cell stress response in C3KO muscles, and that
      these characteristics are pathological features of LGMD2A.

PMID- 15961412
TI  - A direct gene transfer strategy via brain internal capsule reverses the
      biochemical defect in Tay-Sachs disease.
AB  - Therapy for neurodegenerative lysosomal Tay-Sachs (TS) disease requires active
      hexosaminidase (Hex) A production in the central nervous system and an efficient
      therapeutic approach that can act faster than human disease progression. We
      combined the efficacy of a non-replicating Herpes simplex vector encoding for the
      Hex A alpha-subunit (HSV-T0alphaHex) and the anatomic structure of the brain
      internal capsule to distribute the missing enzyme optimally. With this gene
      transfer strategy, for the first time, we re-established the Hex A activity and
      totally removed the GM2 ganglioside storage in both injected and controlateral
      hemispheres, in the cerebellum and spinal cord of TS animal model in the span of
      one month's treatment. In our studies, no adverse effects were observed due to
      the viral vector, injection site or gene expression and on the basis of these
      results, we feel confident that the same approach could be applied to similar
      diseases involving an enzyme defect.

PMID- 15961413
TI  - Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.
AB  - Recently targeted disruption of Omi/HtrA2 has been found to cause
      neurodegeneration and a parkinsonian phenotype in mice. Using a candidate gene
      approach, we performed a mutation screening of the Omi/HtrA2 gene in German
      Parkinson's disease (PD) patients. In four patients, we identified a novel
      heterozygous G399S mutation, which was absent in healthy controls. Moreover, we
      identified a novel A141S polymorphism that was associated with PD (P<0.05). Both
      mutations resulted in defective activation of the protease activity of Omi/HtrA2.
      Immunohistochemistry and functional analysis in stably transfected cells revealed
      that S399 mutant Omi/HtrA2 and to a lesser extent, the risk allele of the A141S
      polymorphism induced mitochondrial dysfunction associated with altered
      mitochondrial morphology. Cells overexpressing S399 mutant Omi/HtrA2 were more
      susceptible to stress-induced cell death than wild-type. On the basis of
      functional genomics, our results provide a novel link between mitochondrial
      dysfunction and neurodegeneration in PD.

PMID- 15961414
TI  - Frataxin interacts functionally with mitochondrial electron transport chain
      proteins.
AB  - Frataxin deficiency is the main cause of Friedreich ataxia, an autosomal
      recessive neurodegenerative disorder. Frataxin function in mitochondria has not
      been fully explained yet. In this work, we show that Saccharomyces cerevisiae
      frataxin orthologue Yfh1p interacts physically with succinate dehydrogenase
      complex subunits Sdh1p and Sdh2p of the yeast mitochondrial electron transport
      chain and also with electron transfer flavoprotein complex ETFalpha and ETFbeta
      subunits from the electron transfer flavoprotein complex. Genetic synthetic
      interaction experiments confirmed a functional relationship between YFH1 and
      succinate dehydrogenase genes SDH1 and SDH2. We also demonstrate a physical
      interaction between human frataxin and human succinate dehydrogenase complex
      subunits, suggesting also a key role of frataxin in the mitochondrial electron
      transport chain in humans. Consequently, we suggest a direct participation of the
      respiratory chain in the pathogenesis of the Friedreich ataxia, which we propose
      to be considered as an OXPHOS disease.

PMID- 15961415
TI  - Knowledge management.

PMID- 15961416
TI  - TRP channels in Drosophila photoreceptor cells.
AB  - TRP cation channels are conserved throughout animal phylogeny and include many
      members that function in sensory physiology. The founding TRP is required for
      Drosophila phototransduction and has served as a paradigm for unravelling the
      roles and macromolecular organizations of TRP channels in native tissues. Two
      other TRPC channels, TRPL and TRPgamma, are expressed in photoreceptor cells and
      form heteromultimers with TRP and with each other. TRP is a member of a
      supramolecular signalling complex, the signalplex, which includes the PDZ
      scaffold protein, INAD, and two other core members that remain bound and depend
      on INAD for localization. Other INAD binding proteins are proposed to interact
      dynamically with INAD, one of which, TRPL, undergoes light-dependent
      translocation in photoreceptor cells. Surprisingly, TRP has non-channel
      functions, including an anchoring role necessary for retaining INAD in the
      rhabdomeres. Loss of TRP function or constitutive TRP activity results in retinal
      degeneration, which can be suppressed by disruption or overexpression of the
      Na+/Ca2+ exchanger, CalX, respectively. Given that hypoxia-induced constitutive
      activity of some mammalian TRPs leads to neuronal cell death, interventions that
      increase Na+/Ca2+ exchanger or decrease TRP function have the potential to reduce
      the severity of cell death due to ischaemia.

PMID- 15961417
TI  - Mitofusins 1/2 and ERRalpha expression are increased in human skeletal muscle
      after physical exercise.
AB  - Mitochondrial impairment is hypothesized to contribute to the pathogenesis of
      insulin resistance. Mitofusin (Mfn) proteins regulate the biogenesis and
      maintenance of the mitochondrial network, and when inactivated, cause a failure
      in the mitochondrial architecture and decreases in oxidative capacity and glucose
      oxidation. Exercise increases muscle mitochondrial content, size, oxidative
      capacity and aerobic glucose oxidation. To address if Mfn proteins are implicated
      in these exercise-induced responses, we measured Mfn1 and Mfn2 mRNA levels, pre-,
      post-, 2 and 24 h post-exercise. Additionally, we measured the expression levels
      of transcriptional regulators that control mitochondrial biogenesis and
      functions, including PGC-1alpha, NRF-1, NRF-2 and the recently implicated
      ERRalpha. We show that Mfn1, Mfn2, NRF-2 and COX IV mRNA were increased 24 h post
      exercise, while PGC-1alpha and ERRalpha mRNA increased 2 h post-exercise.
      Finally, using in vitro cellular assays, we demonstrate that Mfn2 gene expression
      is driven by a PGC-1alpha programme dependent on ERRalpha. The PGC
      1alpha/ERRalpha-mediated induction of Mfn2 suggests a role of these two factors
      in mitochondrial fusion. Our results provide evidence that PGC-1alpha not only
      mediates the increased expression of oxidative phosphorylation genes but also
      mediates alterations in mitochondrial architecture in response to aerobic
      exercise in humans.

PMID- 15961418
TI  - Calcium feedback mechanisms regulate oscillatory activity of a TRP-like Ca2+
      conductance in C. elegans intestinal cells.
AB  - Inositol-1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations in Caenorhabditis
      elegans intestinal epithelial cells regulate the nematode defecation cycle. The
      role of plasma membrane ion channels in intestinal cell oscillatory Ca2+
      signalling is unknown. We have shown previously that cultured intestinal cells
      express a Ca2+-selective conductance, I(ORCa), that is biophysically similar to
      TRPM7 currents. I(ORCa) activates slowly and stabilizes when cells are patch
      clamped with pipette solutions containing 10 mm BAPTA and free Ca2+
      concentrations of approximately 17 nm. However, when BAPTA concentration is
      lowered to 1 mm, I(ORCa) oscillates. Oscillations in channel activity induced
      simultaneous oscillations in cytoplasmic Ca2+ levels. Removal of extracellular
      Ca2+ inhibited I(ORCa) oscillations, whereas readdition of Ca2+ to the bath
      caused a rapid and transient reactivation of the current. Experimental manoeuvres
      that elevated intracellular Ca2+ blocked current oscillations. Elevation of
      intracellular Ca2+ in the presence of 10 mm BAPTA to block I(ORCa) oscillations
      led to a dose-dependent increase in the rate of current activation. At
      intracellular Ca2+ concentrations of 250 nm, current activation was transient.
      Patch pipette solutions buffered with 1-4 mm of either BAPTA or EGTA gave rise to
      similar patterns of I(ORCa) oscillations. We conclude that changes in Ca2+
      concentration close to the intracellular opening of the channel pore regulate
      channel activity. Low concentrations of Ca2+ activate the channel. As Ca2+ enters
      and accumulates near the pore mouth, channel activity is inhibited. Oscillating
      plasma membrane Ca2+ entry may play a role in generating intracellular Ca2+
      oscillations that regulate the C. elegans defecation rhythm.

PMID- 15961419
TI  - Increased uncoupling protein-2 mRNA abundance and glucocorticoid action in
      adipose tissue in the sheep fetus during late gestation is dependent on plasma
      cortisol and triiodothyronine.
AB  - The endocrine regulation of uncoupling protein-2 (UCP2), an inner mitochondrial
      protein, in fetal adipose tissue remains unclear. The present study aimed to
      determine if fetal plasma cortisol and triiodothyronine (T3) influenced the mRNA
      abundance of UCP2, glucocorticoid receptor (GR) and 11beta-hydroxysteroid
      dehydrogenase type 1 (11betaHSD1) and 2 (11betaHSD2) in fetal adipose tissue in
      the sheep during late gestation. Perirenal-abdominal adipose tissue was sampled
      from ovine fetuses to which either cortisol (2-3 mg kg(-1) day(-1)) or saline was
      infused for 5 days up to 127-130 days gestation, or near term fetuses (i.e. 142
      145 days gestation) that were either adrenalectomised (AX) or remained intact.
      Fetal plasma cortisol and T3 concentrations were higher in the cortisol infused
      animals and lower in AX fetuses compared with their corresponding control group,
      and increased with gestational age. UCP2 and GR mRNA abundance were significantly
      lower in AX fetuses compared with age-matched controls, and increased with
      gestational age and by cortisol infusion. Glucocorticoid action in fetal adipose
      tissue was augmented by AX and suppressed by cortisol infusion, the latter also
      preventing the gestational increase in 11betaHSD1 mRNA and decrease in 11betaHSD2
      mRNA. When all treatment groups were combined, both fetal plasma cortisol and T3
      concentrations were positively correlated with UCP2, GR and 11betaHSD2 mRNA
      abundance, but negatively correlated with 11betaHSD1 mRNA abundance. In
      conclusion, plasma cortisol and T3 are both required for the late gestation rise
      in UCP2 mRNA and differentially regulate glucocorticoid action in fetal adipose
      tissue in the sheep during late gestation.

PMID- 15961420
TI  - Modulation of calcium currents is eliminated after cleavage of a strategic
      component of the mammalian secretory apparatus.
AB  - Adenosine inhibits neurotransmitter secretion from motor nerves by an effect on
      the secretory apparatus in amphibia. In contrast, the inhibitory effect of
      adenosine is associated with decreases in calcium currents at mouse motor nerve
      endings. To determine if the action of adenosine in the mouse is mediated
      thorough a direct effect on calcium channels or through the secretory machinery,
      the effects of cleavage of the SNARE proteins on the action of adenosine were
      examined. Cleavage of the SNARE syntaxin with botulinum toxin type C (Botx/C)
      prevented the inhibitory effect of adenosine on nerve terminal calcium currents.
      Cleavage of the other SNAREs (synaptobrevin with Botx/D or SNAP-25 with Botx/A)
      failed to affect the inhibitory action of adenosine. The results provide evidence
      for an intimate coupling of nerve terminal calcium channels with a plasma
      membrane component of the SNARE complex, such that modulation of calcium currents
      by a G-protein coupled receptor cannot occur when syntaxin is cleaved.

PMID- 15961421
TI  - Impedance control and internal model use during the initial stage of adaptation
      to novel dynamics in humans.
AB  - This study investigated the neuromuscular mechanisms underlying the initial stage
      of adaptation to novel dynamics. A destabilizing velocity-dependent force field
      (VF) was introduced for sets of three consecutive trials. Between sets a random
      number of 4-8 null field trials were interposed, where the VF was inactivated.
      This prevented subjects from learning the novel dynamics, making it possible to
      repeatedly recreate the initial adaptive response. We were able to investigate
      detailed changes in neural control between the first, second and third VF trials.
      We identified two feedforward control mechanisms, which were initiated on the
      second VF trial and resulted in a 50% reduction in the hand path error. Responses
      to disturbances encountered on the first VF trial were feedback in nature, i.e.
      reflexes and voluntary correction of errors. However, on the second VF trial,
      muscle activation patterns were modified in anticipation of the effects of the
      force field. Feedforward cocontraction of all muscles was used to increase the
      viscoelastic impedance of the arm. While stiffening the arm, subjects also
      exerted a lateral force to counteract the perturbing effect of the force field.
      These anticipatory actions indicate that the central nervous system responds
      rapidly to counteract hitherto unfamiliar disturbances by a combination of
      increased viscoelastic impedance and formation of a crude internal dynamics
      model.

PMID- 15961422
TI  - Furosemide-induced renal medullary hypoperfusion in the rat: role of tissue
      tonicity, prostaglandins and angiotensin II.
AB  - Furosemide (frusemide)-induced renal medullary hypoperfusion provides a model for
      studies of the dependence of local circulation on tissue tonicity. We examined
      the role of medullary prostaglandins (PG) and adenosine (Ado) as possible
      mediators of the response to furosemide. Furosemide was infused i.v. at 0.25 mg
      kg(-1) h(-1) in anaesthetized rats, untreated or treated with intramedullary
      indomethacin (Indo) or Ado. An integrated set-up was used to measure renal
      medullary laser-Doppler flux (MBF) and medullary ionic tonicity (electrical
      admittance, Y), and to infuse Indo and Ado directly into the medulla. The
      cortical flux was measured on kidney surface. The excretion of water, sodium and
      total solute was also determined. Intramedullary Indo (1 mg kg(-1) h(-1))
      decreased MBF 18 +/- 5% and increased tissue Y 14 +/- 3% (both significant); the
      treatment abolished the post-furosemide decrease in MBF (-22% in untreated group)
      and enhanced slightly the increase in renal excretion. Intramedullary Ado (5 mg
      kg(-1) h(-1)) did not change baseline MBF or Y; the post-furosemide decreases in
      MBF (-22%) and Y, and the increase in renal excretion were preserved. We conclude
      that a decrease in intramedullary PG activity secondary to decreased medullary
      hypertonicity mediates the fall in medullary perfusion in response to furosemide;
      the hypoperfusion may help restore the initial tonicity. Together with the
      earlier evidence on the dependence of post-furosemide medullary hypoperfusion on
      angiotensin II, the study exposes its interaction with PG in the control of
      medullary circulation. Adenosine is not involved in medullary vascular responses
      to decreased tissue hypertonicity.

PMID- 15961423
TI  - Characterization of a proton-activated, outwardly rectifying anion channel.
AB  - Anion channels are present in every mammalian cell and serve many different
      functions, including cell volume regulation, ion transport across epithelia,
      regulation of membrane potential and vesicular acidification. Here we
      characterize a proton-activated, outwardly rectifying current endogenously
      expressed in HEK293 cells. Binding of three to four protons activated the anion
      permeable channels at external pH below 5.5 (50% activation at pH 5.1). The
      proton-activated current is strongly outwardly rectifying, due to an outwardly
      rectifying single channel conductance and an additional voltage dependent
      facilitation at depolarized membrane potentials. The anion channel blocker 4,4'
      diisothiocyanostilbene-2,2'-disulphonic acid (DIDS) rapidly and potently
      inhibited the channel (IC50: 2.9 microm). Flufenamic acid blocked this channel
      only slowly, while mibefradil and amiloride at high concentrations had no effect.
      As determined from reversal potential measurements under bi-ionic conditions, the
      relative permeability sequence of this channel was SCN-> I-> NO3-> Br-> Cl-. None
      of the previously characterized anion channel matches the properties of the
      proton-activated, outwardly rectifying channel. Specifically, the proton
      activated and the volume-regulated anion channels are two distinct and separable
      populations of ion channels, each having its own set of biophysical and
      pharmacological properties. We also demonstrate endogenous proton-activated
      currents in primary cultured hippocampal astrocytes. The proton-activated current
      in astrocytes is also carried by anions, strongly outwardly rectifying, voltage
      dependent and inhibited by DIDS. Proton-activated, outwardly rectifying anion
      channels therefore may be a broadly expressed part of the anionic channel
      repertoire of mammalian cells.

PMID- 15961424
TI  - A single air dive reduces arterial endothelial function in man.
AB  - During and after decompression from dives, gas bubbles are regularly observed in
      the right ventricular outflow tract. A number of studies have documented that
      these bubbles can lead to endothelial dysfunction in the pulmonary artery but no
      data exist on the effect of diving on arterial endothelial function. The present
      study investigated if diving or oxygen breathing would influence endothelial
      arterial function in man. A total of 21 divers participated in this study. Nine
      healthy experienced male divers with a mean age of 31 +/- 5 years were compressed
      in a hyperbaric chamber to 280 kPa at a rate of 100 kPa min(-1) breathing air and
      remaining at pressure for 80 min. The ascent rate during decompression was 9 kPa
      min(-1) with a 7 min stop at 130 kPa (US Navy procedure). Another group of five
      experienced male divers (31 +/- 6 years) breathed 60% oxygen (corresponding to
      the oxygen tension of air at 280 kPa) for 80 min. Before and after exposure,
      endothelial function was assessed in both groups as flow-mediated dilatation
      (FMD) by ultrasound in the brachial artery. The results were compared to data
      obtained from a group of seven healthy individuals of the same age who had never
      dived. The dive produced few vascular bubbles, but a significant arterial
      diameter increase from 4.5 +/- 0.7 to 4.8 +/- 0.8 mm (mean +/- s.d.) and a
      significant reduction of FMD from 9.2 +/- 6.9 to 5.0 +/- 6.7% were observed as an
      indication of reduced endothelial function. In the group breathing oxygen,
      arterial diameter increased significantly from 4.4 +/- 0.3 mm to 4.7 +/- 0.3 mm,
      while FMD showed an insignificant decrease. Oxygen breathing did not decrease
      nitroglycerine-induced dilatation significantly. In the normal controls the
      arterial diameter and FMD were 4.1 +/- 0.4 mm and 7.7 +/- 0.2.8%, respectively.
      This study shows that diving can lead to acute arterial endothelial dysfunction
      in man and that oxygen breathing will increase arterial diameter after return to
      breathing air. Further studies are needed to determine if these mechanisms are
      involved in tissue injury following diving.

PMID- 15961425
TI  - Early expression of KCC2 in rat hippocampal cultures augments expression of
      functional GABA synapses.
AB  - The development of GABAergic synapses is associated with an excitatory to
      inhibitory shift of the actions of GABA because of a reduction of [Cl-]i. This is
      due to a delayed postnatal expression of the K+ -Cl- cotransporter KCC2, which
      has low levels at birth and peaks during the first few postnatal weeks. Whether
      the expression of the cotransporter and the excitatory to inhibitory shift have
      other consequences on the operation of GABA(A) receptors and synapses is not yet
      known. We have now expressed KCC2 in immature neurones at an early developmental
      stage and determined the consequences on the formation of GABA and glutamate
      synapses. We report that early expression of the cotransporter selectively
      enhances GABAergic synapses: there is a significant increase of the density of
      GABA(A) receptors and synapses and an increase of the frequency of GABAergic
      miniature postsynaptic currents. The density of glutamate synapses and frequency
      of AMPA miniature postsynaptic currents are not affected. We conclude that the
      expression of KCC2 and the reduction of [Cl-]i play a critical role in the
      construction of GABAergic networks that extends beyond the excitatory to
      inhibitory shift of the actions of GABA.

PMID- 15961426
TI  - The structural basis of the increase in isometric force production with
      temperature in frog skeletal muscle.
AB  - X-ray diffraction patterns were recorded from isolated single fibres of frog
      skeletal muscle during isometric contraction at temperatures between 0 and 17
      degrees C. Isometric force was 43 +/- 2% (mean +/- S.E.M., n = 10) higher at 17
      degrees C than 0 degrees C. The intensity of the first actin layer line increased
      by 57 +/- 18% (n = 5), and the ratio of the intensities of the equatorial 1,1 and
      1,0 reflections by 20 +/- 7% (n = 10), signalling radial or azimuthal motions of
      the myosin head domains. The M3 X-ray reflection from the axial repeat of the
      heads along the filaments was 27 +/- 4% more intense at 17 degrees C, suggesting
      that the heads became more perpendicular to the filaments. The ratio of the
      intensities of the higher and lower angle peaks of the M3 reflection (R(M3)) was
      0.93 +/- 0.02 (n = 5) at 0 degrees C and 0.77 +/- 0.02 at 17 degrees C. These
      peaks are due to interference between the two halves of each myosin filament, and
      the R(M3) decrease shows that heads move towards the midpoint of the myosin
      filament at the higher temperature. Calculations based on a crystallographic
      model of the heads indicated that the observed R(M3) change corresponds to
      tilting of their light-chain domains by 9 deg, producing an axial displacement of
      1.4 nm, which is equal to that required to strain the actin and myosin filaments
      under the increased force. We conclude that the higher force generated by
      skeletal muscle at higher temperature can be accounted for by axial tilting of
      the myosin heads.

PMID- 15961427
TI  - The involvement of Cav3.2/alpha1H T-type calcium channels in excitability of
      mouse embryonic primary vestibular neurones.
AB  - Ca2+ influx through voltage-gated calcium channels probably influences neuronal
      ontogenesis. Many developing neurones transiently express T-type/Cav3 calcium
      channels that contribute to their electrical activity and potentially to their
      morphological differentiation. Here we have characterized the
      electrophysiological properties and the functional role of a large T-type calcium
      current that is present in mouse developing primary vestibular neurones at
      embryonic day E17. This T-type current showed fast activation and inactivation,
      as well as slow deactivation kinetics. The overlap of activation and inactivation
      parameters produced a window current between -65 and -45 mV. Recovery from short
      term inactivation was slow suggesting the presence of the Cav3.2 subunit. This T
      type current was blocked by micromolar concentrations of Ni2+ and was inhibited
      by fast perfusion velocities in a similar fashion to recombinant Cav3.2 T-type
      channels expressed in HEK-293 cells. More importantly, current clamp experiments
      have revealed that the T-current could elicit afterdepolarization potentials
      during the repolarization phase of action potentials, and occasionally generate
      calcium spikes. Taken together, we demonstrate that the Cav3.2 subunit is likely
      to be the main T-type calcium channel subunit expressed in embryonic vestibular
      neurones and should play a key role in the excitability of these neurones during
      the ontogenesis of vestibular afferentation.

PMID- 15961428
TI  - TRPV4 plays an evolutionary conserved role in the transduction of osmotic and
      mechanical stimuli in live animals.
AB  - The TRPV4 ion channel, previously named vanilloid receptor-related osmotically
      activated channel (VR-OAC), functions in vivo in the transduction of osmotic and
      mechanical stimuli. In trpv4 null mice, TRPV4 was found to be necessary for the
      maintenance of systemic osmotic equilibrium, and for normal thresholds in
      response to noxious mechanical stimuli. In a Caenorhabditis elegans TRPV mutant
      transgenic for mammalian TRPV4, the mammalian transgene was directing the osmotic
      and mechanical avoidance response in the context of the ASH 'nociceptive'
      neurone. Molecular mechanisms of gating of TRPV4 in vivo are not known at this
      point and have to be determined.

PMID- 15961429
TI  - Cooling blocks rat hippocampal neurotransmission by a presynaptic mechanism:
      observations using 2-photon microscopy.
AB  - Over the past decade there has been great interest in the therapeutic potential
      of brain cooling for epilepsy, stroke, asphyxia and other neurological diseases.
      However, there is still no consensus regarding the neurophysiological effect(s)
      of brain cooling. We employed standard physiological techniques and 2-photon
      microscopy to directly examine the effect of temperature on evoked
      neurotransmitter release in rat hippocampal slices. We observed a monotonic
      decline in extracellular synaptic potentials and their initial slope over the
      temperature range 33-20 degrees C, when the slices were cooled to a new set point
      in less than 5 s. Imaging the fluorescent synaptic marker FM1-43 with 2-photon
      microscopy showed that the same cooling protocol dramatically reduced transmitter
      release between 33 and 20 degrees C. Cooling also reduced the terminal FM1-43
      destaining that was induced by direct depolarization with elevated K+, indicating
      that axonal conduction block cannot account for our observations. The temperature
      dependence of FM1-43 destaining correlated well with the effect of temperature on
      field potential slope, compatible with a presynaptic explanation for our
      electrophysiological observations. Optical measurement of FM1-43 dissociation
      from cell membranes was not affected by temperature, and rapid cooling of slices
      loaded with FM1-43 did not increase their fluorescence. Our experiments provide
      visible evidence that a major neurophysiological effect of cooling in the
      mammalian brain is a reduction in the efficacy of neurotransmitter release. This
      presynaptic effect may account for some of the therapeutic benefits of cooling in
      epilepsy and possibly stroke.

PMID- 15961430
TI  - Size selectivity of hyaluronan molecular sieving by extracellular matrix in
      rabbit synovial joints.
AB  - In joint fluid the polymer hyaluronan (HA) confers viscous lubrication and
      greatly attenuates trans-synovial fluid loss (outflow buffering). Outflow
      buffering arises from the molecular sieving (reflection) and concentration
      polarization of HA at the synovial membrane surface. Outflow buffering declines
      if HA chain length is reduced, as in arthritis, and this has been attributed to
      reduced HA reflection. This was tested directly in the present study. Infused
      solutions of HA of approximately 2200 kDa (HA2000, 0.2 mg ml(-1)) or
      approximately 500 kDa (HA500, 0.2 mg ml(-1)) or approximately 140 kDa (HA140, 0.2
      4.0 mg ml(-1)) were filtered across the synovial lining of the knee joint cavity
      of anaesthetized rabbits at a constant rate, along with a freely permeating
      reference solute, 20 kDa fluorescein-dextran (FD20). After a priming period the
      femoral lymph was sampled over 3 h. Mixed intra-articular (i.a.) fluid and
      subsynovial fluid were sampled at the end. Fluids were analysed by gel exclusion
      chromatography. The trans-synovial concentration profile was found to depend on
      polymer size. The i.a. concentration of HA2000 increased substantially relative
      to infusate and the subsynovial and lymph concentrations fell substantially. For
      HA500 and HA140 the trans-synovial concentration gradients were less pronounced,
      and absent for FD. The reflected fractions for HA2000, HA500 and HA140 across the
      cavity-to-lymph barrier were 0.65 +/- 0.05 (n = 10), 0.43 +/- 0.09 (n = 3) and
      0.19 +/- 0.05 (n = 7), respectively, at matched filtration rates (P < 0.0001,
      analysis of variance). Reflected fractions calculated from HA i.a. accumulation
      or subsynovial dilution showed the same trend. The results demonstrate size
      selective molecular sieving by the synovial extracellular matrix, equivalent to
      steric exclusion from cylindrical pores of radius 33-59 nm. The findings underpin
      the concentration polarization-outflow buffering theory and indicate that reduced
      HA chain length in arthritis exacerbates lubricant loss from a joint.

PMID- 15961431
TI  - P2X2 knockout mice and P2X2/P2X3 double knockout mice reveal a role for the P2X2
      receptor subunit in mediating multiple sensory effects of ATP.
AB  - Extracellular ATP plays a role in nociceptive signalling and sensory regulation
      of visceral function through ionotropic receptors variably composed of P2X2 and
      P2X3 subunits. P2X2 and P2X3 subunits can form homomultimeric P2X2,
      homomultimeric P2X3, or heteromultimeric P2X2/3 receptors. However, the relative
      contribution of these receptor subtypes to afferent functions of ATP in vivo is
      poorly understood. Here we describe null mutant mice lacking the P2X2 receptor
      subunit (P2X2-/-) and double mutant mice lacking both P2X2 and P2X3 subunits
      (P2X2/P2X3(Dbl-/-)), and compare these with previously characterized P2X3-/-
      mice. In patch-clamp studies, nodose, coeliac and superior cervical ganglia (SCG)
      neurones from wild-type mice responded to ATP with sustained inward currents,
      while dorsal root ganglia (DRG) neurones gave predominantly transient currents.
      Sensory neurones from P2X2-/- mice responded to ATP with only transient inward
      currents, while sympathetic neurones had barely detectable responses. Neurones
      from P2X2/P2X3(Dbl-/-) mice had minimal to no response to ATP. These data
      indicate that P2X receptors on sensory and sympathetic ganglion neurones involve
      almost exclusively P2X2 and P2X3 subunits. P2X2-/- and P2X2/P2X3(Dbl-/-) mice had
      reduced pain-related behaviours in response to intraplantar injection of
      formalin. Significantly, P2X3-/-, P2X2-/-, and P2X2/P2X3(Dbl-/-) mice had reduced
      urinary bladder reflexes and decreased pelvic afferent nerve activity in response
      to bladder distension. No deficits in a wide variety of CNS behavioural tests
      were observed in P2X2-/- mice. Taken together, these data extend our findings for
      P2X3-/- mice, and reveal an important contribution of heteromeric P2X2/3
      receptors to nociceptive responses and mechanosensory transduction within the
      urinary bladder.

PMID- 15961433
TI  - Determinants of prescribing of second-choice antibiotics for upper and lower
      respiratory tract episodes in Dutch general practice.
AB  - OBJECTIVES: The aim of this study was to assess the association between general
      practitioners' (GPs') characteristics and the volume of second-choice antibiotics
      for acute respiratory tract (RT) episodes by GPs. METHODS: Morbidity and
      antibiotic prescription data originated from the Second Dutch National Survey of
      General Practice (DNSGP-2). GPs' characteristics, including professional
      activities and views on RT symptoms and antibiotics, were measured by a written
      questionnaire. Multiple regression was carried out to assess associations between
      possible determinants and volume of second-choice antibiotic prescriptions.
      RESULTS: In approximately 39% of acute RT episodes antibiotics were prescribed,
      with one-quarter being second-choice antibiotics, relatively more frequently in
      lower than in upper RT episodes: 30 versus 19%. GPs who were more frequently
      consulted by patients with RT episodes (beta = 0.29; 95% CI 0.13-0.41), who
      labelled RT episodes more as diagnoses than as symptoms (beta = 0.27; 95% CI 0.15
      0.42), who less frequently used national GP guidelines (beta = -0.17; 95% CI 
      0.31 to -0.03) and who were more inclined to prescribe new drugs (beta = 0.26;
      95% CI 0.13-0.40), prescribed more second-choice antibiotics. CONCLUSIONS: Given
      the growing number of prescriptions of second-choice antibiotics, it is important
      to implement professional guidelines in daily practice, while training in being
      reluctant to prescribe new drugs and being alert to the marketing activities of
      pharmaceutical companies should be started in the medical curriculum.

PMID- 15961432
TI  - The contribution of TRPM8 channels to cold sensing in mammalian neurones.
AB  - Different classes of ion channels have been implicated in sensing cold
      temperatures at mammalian thermoreceptor nerve endings. A major candidate is
      TRPM8, a non-selective cation channel of the transient receptor potential family,
      activated by menthol and low temperatures. We investigated the role of TRPM8 in
      cold sensing during transient expression in mouse cultured hippocampal neurones,
      a tissue that lacks endogenous expression of thermosensitive TRPs. In the absence
      of synaptic input, control hippocampal neurones were not excited by cooling. In
      contrast, all TRPM8-transfected hippocampal neurones were excited by cooling and
      menthol. However, in comparison to cold-sensitive trigeminal sensory neurones,
      hippocampal neurones exhibited much lower threshold temperatures, requiring
      temperatures below 27 degrees C to fire action potentials. These results directly
      demonstrate that expression of TRPM8 in mammalian neurones induces cold sensing,
      albeit at lower temperatures than native TRPM8-expressing neurones, suggesting
      the presence of additional modulatory mechanisms in the cold response of sensory
      neurones.

PMID- 15961434
TI  - Psychiatric disorders following first breast cancer recurrence: prevalence,
      associated factors and relationship to quality of life.
AB  - OBJECTIVE: The purpose of this study was to investigate the prevalence of and
      factors associated with psychiatric disorders and the impact on quality of life
      (QOL) in patients with first breast cancer recurrence. METHODS: We analyzed the
      baseline data on 50 consecutively enrolled recurrent breast cancer patients,
      participating in a feasibility study of multifaceted psychosocial intervention.
      Psychiatric disorders, including major depressive disorder (MDD), dysthymic
      disorder, panic disorder, post-traumatic stress disorder (PTSD), generalized
      anxiety disorder and adjustment disorders (AD), were evaluated according to the
      Structured Clinical Interview for the DSM-III-R and IV. The patients' demographic
      data, biomedical factors, social support, mental adjustment to cancer,
      personality traits and QOL were also evaluated. RESULTS: Eleven (22%) met the DSM
      III-R and IV criteria for MDD, PTSD or AD (MDD, 2%; PTSD, 2%; AD, 20%).
      Univariate analysis indicated that current doxorubicin/cyclophosphamide, presence
      of a confidant, past history of MDD, helplessness/hopelessness and neuroticism
      were significantly associated with psychiatric disorders. On multivariate
      logistic regression analysis, past history of MDD and helplessness/hopelessness
      were significant associated factors. Psychiatric disorders were significantly
      associated with lower functional scales ('emotional functioning', 'body image'
      and 'future perspective') and higher symptom scales ('appetite loss', 'diarrhea',
      'fatigue' and 'nausea-vomiting') in QOL. CONCLUSIONS: The result suggests that
      asking about history of depression and appropriate intervention, including psycho
      education, are needed for patients with first breast cancer recurrence in order
      to detect and manage psychological distress. Although further studies are needed
      to clarify causal links between psychiatric disorders and QOL, patients'
      psychiatric disorders were associated with QOL.

PMID- 15961435
TI  - Phase I evaluation of continuous 5-fluorouracil infusion followed by weekly
      paclitaxel in patients with advanced or recurrent gastric cancer.
AB  - OBJECTIVE: We conducted a phase I trial of escalating doses of weekly paclitaxel
      (Taxol) in combination with a fixed systemic administration of 5-fluorouracil (5
      FU) in patients with advanced or metastatic gastric cancer. METHODS: Patients
      with advanced or recurrent gastric cancer were treated with escalating doses of
      weekly paclitaxel as a 60 min intravenous (i.v.) infusion, along with a fixed
      dose of continuous 5-FU infused over 5 days. Plasma sampling was performed to
      characterize the pharmacokinetics and pharmacodynamics of paclitaxel. RESULTS:
      Eighteen patients received combination therapy at four dose levels of weekly
      Taxol, ranging from 60 to 90 mg/m2/week. Dose-limiting toxicities > grade 3 were
      observed at the 90 mg/m2/week dose level. Toxicities included anemia,
      neutropenia, thrombocytopenia, nausea and alopecia. Two episodes of grade 4
      neutropenia occurred in two of the three patients receiving this dose. At each
      dose level, pharmacological studies documented the persistence of significant
      serum paclitaxel levels over 24 h after drug administration. The maximum
      tolerated dose (MTD) for this regimen was 90 mg/m2/week of paclitaxel for 3 weeks
      plus 600 mg/m2/day of continuous 5-FU for 5 days. CONCLUSIONS: The combination of
      weekly paclitaxel and 5-FU demonstrated an acceptable toxicity profile and
      feasible pharmacokinetic results suggesting its practical applicability. Based on
      these findings, the recommended dose and schedule for phase II study of
      combination chemotherapy is paclitaxel 80 mg/m2/week x 3 over 4 weeks, and
      continuous 5-FU 600 mg/m2/day x 5 days every 4 weeks.

PMID- 15961436
TI  - Clinical impact of criteria for complete response (CR) of primary site to
      treatment of esophageal cancer.
AB  - BACKGROUND: With the development of chemoradiotherapy for esophageal cancer, the
      complete response (CR) rate would become an important surrogate end-point.
      However, the Response Evaluation Criteria in Solid Tumors (RECIST) do not provide
      criteria for a response at the primary site of esophageal cancer. The objective
      of this study was to assess the validity of the endoscopic CR criteria for the
      primary site of esophageal cancer treated with chemoradiotherapy. METHODS: We
      reviewed 139 patients with T1-T4, N0-1, M0-1a esophageal cancer treated with
      definitive chemoradiotherapy from August 1992 to April 1999. CR was tentatively
      defined upon endoscopic observation of the entire esophagus as: (i) disappearance
      of the tumor lesion; (ii) disappearance of ulceration (slough); and (iii) absence
      of cancer cells in biopsy specimens. RESULTS: CR at the primary site (primary-CR)
      was achieved in 80 patients (58%). Of these, 71 (89%) were evaluated as having
      primary-CR within 6 months from the start of therapy. With a median follow-up of
      53 months, a remarkable difference in the 5-year survival rate was observed
      between patients evaluated as having primary-CR and having non-CR (46 and 6%, P <
      0.0001). Local failure was observed in 15 patients and the local control rate in
      patients with primary-CR was 78% at 5 years. CONCLUSIONS: These criteria appear
      to represent an appropriate surrogate end-point because they are convenient to
      apply, require only a short time before a primary-CR can be declared and their
      fulfillment can predict long-term survival. It is recommended that RECIST include
      precise endoscopic findings for primary lesions in esophageal cancer in the CR
      criteria.

PMID- 15961437
TI  - Role of protein kinase C-Ras-MAPK p44/42 in ethanol and transforming growth
      factor-beta3-induced basic fibroblast growth factor release from
      folliculostellate cells.
AB  - In the present study, we determined the interactive effects of ethanol and
      transforming growth factor beta-3 (TGF-beta3) on basic fibroblast growth factor
      (bFGF) release from folliculostellate (FS) cells and the role of the mitogen
      activated protein kinase (MAPK) pathway in this interaction. We found that TGF
      beta3 and ethanol alone increased release of bFGF from FS cells, but together
      they showed markedly increased levels of bFGF compared with the individual
      effect. Ethanol and TGF-beta3 alone moderately increased activation of MAPK
      p44/42, but together they produced marked activation of MAPK p44/42. TGF-beta3
      alone increased the activation of smad2. Ethanol did not activate smad2 or alter
      TGF-beta3 activation of smad2. Pretreatment of FS cells with a mitogen-activated
      protein kinase kinase 1/2 inhibitor or with a protein kinase C (PKC) inhibitor
      suppressed the TGF-beta3 and ethanol actions on MAPK p44/42 activation and bFGF
      release. Ethanol and TGF-beta3, either alone or in combination, increased the
      levels of active Ras. Furthermore, the MAPK p44/42 activation by TGF-beta3 and
      ethanol was blocked by overexpression of Ras N17, a dominant negative mutant of
      Ras p21. These data suggest that the PKC-activated Ras-dependent MAPK p44/42
      pathway is involved in the cross talk between TGF-beta3 and ethanol to increase
      bFGF release from FS cells.

PMID- 15961438
TI  - MagicMatch--cross-referencing sequence identifiers across databases.
AB  - MOTIVATION: At present, mapping of sequence identifiers across databases is a
      daunting, time-consuming and computationally expensive process, usually achieved
      by sequence similarity searches with strict threshold values. SUMMARY: We present
      a rapid and efficient method to map sequence identifiers across databases. The
      method uses the MD5 checksum algorithm for message integrity to generate sequence
      fingerprints and uses these fingerprints as hash strings to map sequences across
      databases. The program, called MagicMatch, is able to cross-link any of the major
      sequence databases within a few seconds on a modest desktop computer.

PMID- 15961439
TI  - DNA-BAR: distinguisher selection for DNA barcoding.
AB  - DNA-BAR is a software package for selecting DNA probes (henceforth referred to as
      distinguishers) that can be used in genomic-based identification of
      microorganisms. Given the genomic sequences of the microorganisms, DNA-BAR finds
      a near-minimum number of distinguishers yielding a distinct hybridization pattern
      for each microorganism. Selected distinguishers satisfy user specified bounds on
      length, melting temperature and GC content, as well as redundancy and cross
      hybridization constraints.

PMID- 15961440
TI  - Querying and computing with BioCyc databases.
AB  - We describe multiple methods for accessing and querying the complex and
      integrated cellular data in the BioCyc family of databases: access through
      multiple file formats, access through Application Program Interfaces (APIs) for
      LISP, Perl and Java, and SQL access through the BioWarehouse relational database.

PMID- 15961441
TI  - caBIONet--A .NET wrapper to access and process genomic data stored at the
      National Cancer Institute's Center for Bioinformatics databases.
AB  - MOTIVATION: The National Cancer Institute's Center for Bioinformatics (NCICB) has
      developed a Java based data management and information system called caCORE. One
      component of this software suite is the object oriented API (caBIO) used to
      access the rich biological datasets collected at the NCI. This API can access the
      data using native Java classes, SOAP requests or HTTP calls. Non-Java based
      clients wanting to use this API have to use the SOAP or HTTP interfaces with the
      data being returned from the NCI servers as an XML data stream. Although the XML
      can be read and manipulated using DOM or SAX parsers, one loses the convenience
      and usability of an object oriented programming paradigm. caBIONet is a set of
      .NET wrapper classes (managers, genes, chromosomes, sequences, etc.) capable of
      serializing the XML data stream into local .NET objects. The software is able to
      search NCICB databases and provide local objects representing the data that can
      be manipulated and used by other .NET programs. The software was written in C#
      and compiled as a .NET DLL.

PMID- 15961442
TI  - Use of extreme patient samples for outcome prediction from gene expression data.
AB  - MOTIVATION: Patient outcome prediction using microarray technologies is an
      important application in bioinformatics. Based on patients' genotypic microarray
      data, predictions are made to estimate patients' survival time and their risk of
      tumor metastasis or recurrence. So, accurate prediction can potentially help to
      provide better treatment for patients. RESULTS: We present a new computational
      method for patient outcome prediction. In the training phase of this method, we
      make use of two types of extreme patient samples: short-term survivors who got an
      unfavorable outcome within a short period and long-term survivors who were
      maintaining a favorable outcome after a long follow-up time. These extreme
      training samples yield a clear platform for us to identify relevant genes whose
      expression is closely related to the outcome. The selected extreme samples and
      the relevant genes are then integrated by a support vector machine to build a
      prediction model, by which each validation sample is assigned a risk score that
      falls into one of the special pre-defined risk groups. We apply this method to
      several public datasets. In most cases, patients in high and low risk groups
      stratified by our method have clearly distinguishable outcome status as seen in
      their Kaplan-Meier curves. We also show that the idea of selecting only extreme
      patient samples for training is effective for improving the prediction accuracy
      when different gene selection methods are used.

PMID- 15961443
TI  - IRILmap: linkage map distance correction for intermated recombinant inbred
      lines/advanced recombinant inbred strains.
AB  - Intermated Recombinant Inbred Lines (IRILs) in plants, or Advanced Recombinant
      Inbred Strains in animals, are constructed by carrying out generations of
      intermating between F2 individuals before starting recurrent inbreeding
      generations by selfing or sib-mating. IRILs are powerful for high-resolution
      genetic mapping because they have undergone more recombination than usual
      Recombinant Inbred Lines (RILs). However, there is no mapping software able to
      generate actual centiMorgan distances from the segregation data obtained with
      IRILs. IRILmap software converts genetic distances computed with any linkage
      mapping program designed for RILs, so that IRIL-derived data can be used to get
      actual centiMorgan distances, directly comparable to F2, backcross or RIL-derived
      maps.

PMID- 15961444
TI  - The predictive power of the CluSTr database.
AB  - SUMMARY: The CluSTr database employs a fully automatic single-linkage
      hierarchical clustering method based on a similarity matrix. In order to compute
      the matrix, first all-against-all pair-wise comparisons between protein sequences
      are computed using the Smith-Waterman algorithm. The statistical significance of
      the similarity scores is then assessed using a Monte Carlo analysis, yielding Z
      values, which are used to populate the matrix. This paper describes automated
      annotation experiments that quantify the predictive power and hence the
      biological relevance of the CluSTr data. The experiments utilized the UniProt
      data-mining framework to derive annotation predictions using combinations of
      InterPro and CluSTr. We show that this combination of data sources greatly
      increases the precision of predictions made by the data-mining framework,
      compared with the use of InterPro data alone. We conclude that the CluSTr
      approach to clustering proteins makes a valuable contribution to traditional
      protein classifications. AVAILABILITY: http://www.ebi.ac.uk/clustr/.

PMID- 15961445
TI  - Prediction of protein-protein interactions using distant conservation of sequence
      patterns and structure relationships.
AB  - MOTIVATION: Given that association and dissociation of protein molecules is
      crucial in most biological processes several in silico methods have been recently
      developed to predict protein-protein interactions. Structural evidence has shown
      that usually interacting pairs of close homologs (interologs) physically interact
      in the same way. Moreover, conservation of an interaction depends on the
      conservation of the interface between interacting partners. In this article we
      make use of both, structural similarities among domains of known interacting
      proteins found in the Database of Interacting Proteins (DIP) and conservation of
      pairs of sequence patches involved in protein-protein interfaces to predict
      putative protein interaction pairs. RESULTS: We have obtained a large amount of
      putative protein-protein interaction (approximately 130,000). The list is
      independent from other techniques both experimental and theoretical. We separated
      the list of predictions into three sets according to their relationship with
      known interacting proteins found in DIP. For each set, only a small fraction of
      the predicted protein pairs could be independently validated by cross checking
      with the Human Protein Reference Database (HPRD). The fraction of validated
      protein pairs was always larger than that expected by using random protein pairs.
      Furthermore, a correlation map of interacting protein pairs was calculated with
      respect to molecular function, as defined in the Gene Ontology database. It shows
      good consistency of the predicted interactions with data in the HPRD database.
      The intersection between the lists of interactions of other methods and ours
      produces a network of potentially high-confidence interactions.

PMID- 15961447
TI  - ANOSVA: a statistical method for detecting splice variation from expression data.
AB  - MOTIVATION: Many or most mammalian genes undergo alternative splicing, generating
      a variety of transcripts from a single gene. New information on splice variation
      is becoming available through technology for measuring expression levels of
      several exons or splice junctions per gene. We have developed a statistical
      method, ANalysis Of Splice VAriation (ANOSVA) to detect alternative splicing from
      expression data. Since ANOSVA requires no transcript information, it can be
      applied when the level of annotation is poor. When validated against spiked clone
      data, it generated no false positives and few false negatives. We demonstrated
      ANOSVA with data from a prototype mouse alternative splicing array, run against
      normal adult tissues, yielding a set of genes with evidence of tissue-specific
      splice variation. AVAILABILITY: The results are available at the supplementary
      information site. SUPPLEMENTARY INFORMATION: The results are available at the
      supplementary information site https://bioinfo.affymetrix.com/Papers/ANOSVA/

PMID- 15961448
TI  - A path planning approach for computing large-amplitude motions of flexible
      molecules.
AB  - MOTIVATION: Motion is inherent in molecular interactions. Molecular flexibility
      must be taken into account in order to develop accurate computational techniques
      for predicting interactions. Energy-based methods currently used in molecular
      modeling (i.e. molecular dynamics, Monte Carlo algorithms) are, in practice, only
      able to compute local motions while accounting for molecular flexibility.
      However, large-amplitude motions often occur in biological processes. We
      investigate the application of geometric path planning algorithms to compute such
      large motions in flexible molecular models. Our purpose is to exploit the
      efficacy of a geometric conformational search as a filtering stage before
      subsequent energy refinements. RESULTS: In this paper two kinds of large
      amplitude motion are treated: protein loop conformational changes (involving
      protein backbone flexibility) and ligand trajectories to deep active sites in
      proteins (involving ligand and protein side-chain flexibility). First studies
      performed using our two-stage approach (geometric search followed by energy
      refinements) show that, compared to classical molecular modeling methods, quite
      similar results can be obtained with a performance gain of several orders of
      magnitude. Furthermore, our results also indicate that the geometric stage can
      provide highly valuable information to biologists. AVAILABILITY: The algorithms
      have been implemented in the general-purpose motion planning software Move3D,
      developed at LAAS-CNRS. We are currently working on an optimized stand-alone
      library that will be available to the scientific community.

PMID- 15961449
TI  - Detecting coevolving amino acid sites using Bayesian mutational mapping.
AB  - MOTIVATION: The evolution of protein sequences is constrained by complex
      interactions between amino acid residues. Because harmful substitutions may be
      compensated for by other substitutions at neighboring sites, residues can
      coevolve. We describe a Bayesian phylogenetic approach to the detection of
      coevolving residues in protein families. This method, Bayesian mutational mapping
      (BMM), assigns mutations to the branches of the evolutionary tree stochastically,
      and then test statistics are calculated to determine whether a coevolutionary
      signal exists in the mapping. Posterior predictive P-values provide an estimate
      of significance, and specificity is maintained by integrating over uncertainty in
      the estimation of the tree topology, branch lengths and substitution rates. A
      coevolutionary Markov model for codon substitution is also described, and this
      model is used as the basis of several test statistics. RESULTS: Results on
      simulated coevolutionary data indicate that the BMM method can successfully
      detect nearly all coevolving sites when the model has been correctly specified,
      and that non-parametric statistics such as mutual information are generally less
      powerful than parametric statistics. On a dataset of eukaryotic proteins from the
      phosphoglycerate kinase (PGK) family, interdomain site contacts yield a
      significantly greater coevolutionary signal than interdomain non-contacts, an
      indication that the method provides information about interacting sites. Failure
      to account for the heterogeneity in rates across sites in PGK resulted in a less
      discriminating test, yielding a marked increase in the number of reported
      positives at both contact and non-contact sites. SUPPLEMENTARY INFORMATION:
      http://www.dimmic.net/supplement/

PMID- 15961450
TI  - A procedure for assessing GO annotation consistency.
AB  - MOTIVATION: The Gene Ontology (GO) is widely used to annotate molecular
      attributes of genes and gene products. Multiple groups undertaking functional
      annotations of genomes contribute their annotation sets to the GO database
      resource and these data are subsequently used in comparative functional analysis
      research. Although GO curators adhere to the same protocols and standards while
      assigning GO annotations, the specific procedure followed by each annotation
      group can vary. Since differences in application of annotation standards would
      dilute the effectiveness of comparative analysis, methods for assessing
      annotation consistency are essential. The development of methodologies that are
      broadly applicable for the assessment of GO annotation consistency is an
      important issue for the comparative genomics community. RESULTS: We have
      developed a methodology for assessing the consistency of GO annotations provided
      by different annotation groups. The method is completely general and can be
      applied to compare any two sets of GO annotations. This is the first attempt to
      assess cross-species GO annotation consistency. Our method compares annotation
      sets utilizing the hierarchical structure of the GO to compare GO annotations
      between orthologous gene pairs. The method produces a report on the annotation
      consistency and inconsistency for each orthologous pair. We present results
      obtained by comparing GO annotations for mouse and human gene sets. AVAILABILITY:
      The complete current MGI_GOA GO annotation consistency report is available online
      at http://www.spatial.maine.edu/~mdolan/

PMID- 15961451
TI  - Multi-way clustering of microarray data using probabilistic sparse matrix
      factorization.
AB  - MOTIVATION: We address the problem of multi-way clustering of microarray data
      using a generative model. Our algorithm, probabilistic sparse matrix
      factorization (PSMF), is a probabilistic extension of a previous hard-decision
      algorithm for this problem. PSMF allows for varying levels of sensor noise in the
      data, uncertainty in the hidden prototypes used to explain the data and
      uncertainty as to the prototypes selected to explain each data vector. RESULTS:
      We present experimental results demonstrating that our method can better recover
      functionally-relevant clusterings in mRNA expression data than standard
      clustering techniques, including hierarchical agglomerative clustering, and we
      show that by computing probabilities instead of point estimates, our method
      avoids converging to poor solutions.

PMID- 15961452
TI  - PILER: identification and classification of genomic repeats.
AB  - SUMMARY: Repeated elements such as satellites and transposons are ubiquitous in
      eukaryotic genomes. De novo computational identification and classification of
      such elements is a challenging problem. Therefore, repeat annotation of sequenced
      genomes has historically largely relied on sequence similarity to hand-curated
      libraries of known repeat families. We present a new approach to de novo repeat
      annotation that exploits characteristic patterns of local alignments induced by
      certain classes of repeats. We describe PILER, a package of efficient search
      algorithms for identifying such patterns. Novel repeats found using PILER are
      reported for Homo sapiens, Arabidopsis thalania and Drosophila melanogaster.
      AVAILABILITY: The PILER software is freely available at
      http://www.drive5.com/piler.

PMID- 15961453
TI  - Clustering short time series gene expression data.
AB  - MOTIVATION: Time series expression experiments are used to study a wide range of
      biological systems. More than 80% of all time series expression datasets are
      short (8 time points or fewer). These datasets present unique challenges. On
      account of the large number of genes profiled (often tens of thousands) and the
      small number of time points many patterns are expected to arise at random. Most
      clustering algorithms are unable to distinguish between real and random patterns.
      RESULTS: We present an algorithm specifically designed for clustering short time
      series expression data. Our algorithm works by assigning genes to a predefined
      set of model profiles that capture the potential distinct patterns that can be
      expected from the experiment. We discuss how to obtain such a set of profiles and
      how to determine the significance of each of these profiles. Significant profiles
      are retained for further analysis and can be combined to form clusters. We tested
      our method on both simulated and real biological data. Using immune response data
      we show that our algorithm can correctly detect the temporal profile of relevant
      functional categories. Using Gene Ontology analysis we show that our algorithm
      outperforms both general clustering algorithms and algorithms designed
      specifically for clustering time series gene expression data. AVAILABILITY:
      Information on obtaining a Java implementation with a graphical user interface
      (GUI) is available from http://www.cs.cmu.edu/~jernst/st/ SUPPLEMENTARY
      INFORMATION: Available at http://www.cs.cmu.edu/~jernst/st/

PMID- 15961454
TI  - CaSPredictor: a new computer-based tool for caspase substrate prediction.
AB  - MOTIVATION: In vitro studies have shown that the most remarkable catalytic
      features of caspases, a family of cysteineproteases, are their stringent
      specificity to Asp (D) in the S1 subsite and at least four amino acids to the
      left of scissile bound. However, there is little information about the substrate
      recognition patterns in vivo. The prediction and characterization of proteolytic
      cleavage sites in natural substrates could be useful for uncovering these
      structural relationships. RESULTS: PEST-like sequences rich in the amino acids
      Ser (S), Thr (T), Pro (P), Glu or Asp (E/D), including Asn (N) and Gln (Q) are
      adjacent structural/sequential elements in the majority of cleavage site regions
      of the natural caspase substrates described in the literature, supporting its
      possible implication in the substrate selection by caspases. We developed
      CaSPredictor, a software which incorporated a PEST-like index and the position
      dependent amino acid matrices for prediction of caspase cleavage sites in
      individual proteins and protein datasets. The program predicted successfully 81%
      (111/137) of the cleavage sites in experimentally verified caspase substrates not
      annotated in its internal data file. Its accuracy and confidence was estimated as
      80% using ROC methodology. The program was much more efficient in predicting
      caspase substrates when compared with PeptideCutter and PEPS software. Finally,
      the program detected potential cleavage sites in the primary sequences of 1644
      proteins in a dataset containing 9986 protein entries. AVAILABILITY: Requests for
      software should be made to Dr Jose E. Belizario SUPPLEMENTARY INFORMATION:
      Supplementary information is available for academic users at site
      http://icb.usp.br/~farmaco/Jose/CaSpredictorfiles.

PMID- 15961455
TI  - Data integration and visualization system for enabling conceptual biology.
AB  - MOTIVATION: Integration of heterogeneous data in life sciences is a growing and
      recognized challenge. The problem is not only to enable the study of such data
      within the context of a biological question but also more fundamentally, how to
      represent the available knowledge and make it accessible for mining. RESULTS: Our
      integration approach is based on the premise that relationships between
      biological entities can be represented as a complex network. The context
      dependency is achieved by a judicious use of distance measures on these networks.
      The biological entities and the distances between them are mapped for the purpose
      of visualization into the lower dimensional space using the Sammon's mapping. The
      system implementation is based on a multi-tier architecture using a native XML
      database and a software tool for querying and visualizing complex biological
      networks. The functionality of our system is demonstrated with two examples: (1)
      A multiple pathway retrieval, in which, given a pathway name, the system finds
      all the relationships related to the query by checking available metabolic
      pathway, transcriptional, signaling, protein-protein interaction and ontology
      annotation resources and (2) A protein neighborhood search, in which given a
      protein name, the system finds all its connected entities within a specified
      depth. These two examples show that our system is able to conceptually traverse
      different databases to produce testable hypotheses and lead towards answers to
      complex biological questions.

PMID- 15961456
TI  - Identification of nine human-specific frameshift mutations by comparative
      analysis of the human and the chimpanzee genome sequences.
AB  - MOTIVATION: The recent release of the draft sequence of the chimpanzee genome is
      an invaluable resource for finding genome-wide genetic differences that might
      explain phenotypic differences between humans and chimpanzees. AVAILABILITY: In
      this paper, we describe a simple procedure to identify potential human-specific
      frameshift mutations that occurred after the divergence of human and chimpanzee.
      The procedure involves collecting human coding exons bearing insertions or
      deletions compared with the chimpanzee genome and identification of homologs from
      other species, in support of the mutations being human-specific. Using this
      procedure, we identified nine genes, BASE, DNAJB3, FLJ33674, HEJ1, NTSR2,
      RPL13AP, SCGB1D4, WBSCR27 and ZCCHC13, that show human-specific alterations
      including truncations of the C-terminus. In some cases, the frameshift mutation
      results in gene inactivation or decay. In other cases, the altered protein seems
      to be functional. This study demonstrates that even the unfinished chimpanzee
      genome sequence can be useful in identifying modification of genes that are
      specific to the human lineage and, therefore, could potentially be relevant to
      the study of the acquisition of human-specific traits.

PMID- 15961457
TI  - Validation of qualitative models of genetic regulatory networks by model
      checking: analysis of the nutritional stress response in Escherichia coli.
AB  - MOTIVATION: The modeling and simulation of genetic regulatory networks have
      created the need for tools for model validation. The main challenges of model
      validation are the achievement of a match between the precision of model
      predictions and experimental data, as well as the efficient and reliable
      comparison of the predictions and observations. RESULTS: We present an approach
      towards the validation of models of genetic regulatory networks addressing the
      above challenges. It combines a method for qualitative modeling and simulation
      with techniques for model checking, and is supported by a new version of the
      computer tool Genetic Network Analyzer (GNA). The model-validation approach has
      been applied to the analysis of the network controlling the nutritional stress
      response in Escherichia coli. AVAILABILITY: GNA and the model of the stress
      response network are available at http://www-helix.inrialpes.fr/gna.

PMID- 15961458
TI  - Tag SNP selection in genotype data for maximizing SNP prediction accuracy.
AB  - MOTIVATION: The search for genetic regions associated with complex diseases, such
      as cancer or Alzheimer's disease, is an important challenge that may lead to
      better diagnosis and treatment. The existence of millions of DNA variations,
      primarily single nucleotide polymorphisms (SNPs), may allow the fine dissection
      of such associations. However, studies seeking disease association are limited by
      the cost of genotyping SNPs. Therefore, it is essential to find a small subset of
      informative SNPs (tag SNPs) that may be used as good representatives of the rest
      of the SNPs. RESULTS: We define a new natural measure for evaluating the
      prediction accuracy of a set of tag SNPs, and use it to develop a new method for
      tag SNPs selection. Our method is based on a novel algorithm that predicts the
      values of the rest of the SNPs given the tag SNPs. In contrast to most previous
      methods, our prediction algorithm uses the genotype information and not the
      haplotype information of the tag SNPs. Our method is very efficient, and it does
      not rely on having a block partition of the genomic region. We compared our
      method with two state-of-the-art tag SNP selection algorithms on 58 different
      genotype datasets from four different sources. Our method consistently found tag
      SNPs with considerably better prediction ability than the other methods.
      AVAILABILITY: The software is available from the authors on request.

PMID- 15961459
TI  - Enhanced position weight matrices using mixture models.
AB  - MOTIVATION: Positional weight matrix (PWM) is derived from a set of
      experimentally determined binding sites. Here we explore whether there exist
      subclasses of binding sites and if the mixture of these subclass-PWMs can improve
      the binding site prediction. Intuitively, the subclasses correspond to either
      distinct binding preference of the same transcription factor in different
      contexts or distinct subtypes of the transcription factor. AVAILABILITY: We
      report an Expectation Maximization algorithm adapting the mixture model of Baily
      and Elkan. We assessed the relative merit of using two subclass-PWMs. The
      resulting PWMs were evaluated with respect to preferred conservation (relative to
      mouse) of potential sites in human promoters and expression coherence of the
      potential target genes. Based on 64 JASPAR vertebrate PWMs, 61-81% of the cases
      resulted in a higher conservation using the mixture model. Also in 98% of the
      cases the expression coherence was higher for the target genes of one of the
      subclass-PWMs. Our analysis of Reb1 sites is consistent with previously
      discovered subtypes using independent methods. Additionally application of our
      method to mutated sites for transcription factor LEU3 reveals subclasses that
      segregate into strongly binding and weakly binding sites with P-value of 0.008.
      This is the first study which attempts to quantify the subtly different binding
      specificities of a transcription factor on a large scale and suggests the use of
      a mixture of PWMs, instead of the current practice of using a single PWM, for a
      transcription factor.

PMID- 15961460
TI  - Mining coherent dense subgraphs across massive biological networks for functional
      discovery.
AB  - MOTIVATION: The rapid accumulation of biological network data translates into an
      urgent need for computational methods for graph pattern mining. One important
      problem is to identify recurrent patterns across multiple networks to discover
      biological modules. However, existing algorithms for frequent pattern mining
      become very costly in time and space as the pattern sizes and network numbers
      increase. Currently, no efficient algorithm is available for mining recurrent
      patterns across large collections of genome-wide networks. RESULTS: We developed
      a novel algorithm, CODENSE, to efficiently mine frequent coherent dense subgraphs
      across large numbers of massive graphs. Compared with previous methods, our
      approach is scalable in the number and size of the input graphs and adjustable in
      terms of exact or approximate pattern mining. Applying CODENSE to 39 co
      expression networks derived from microarray datasets, we discovered a large
      number of functionally homogeneous clusters and made functional predictions for
      169 uncharacterized yeast genes. AVAILABILITY: http://zhoulab.usc.edu/CODENSE/

PMID- 15961461
TI  - GenXHC: a probabilistic generative model for cross-hybridization compensation in
      high-density genome-wide microarray data.
AB  - MOTIVATION: Microarray designs containing millions to hundreds of millions of
      probes that tile entire genomes are currently being released. Within the next 2
      months, our group will release a microarray data set containing over 12,000,000
      microarray measurements taken from 37 mouse tissues. A problem that will become
      increasingly significant in the upcoming era of genome-wide exon-tiling
      microarray experiments is the removal of cross-hybridization noise. We present a
      probabilistic generative model for cross-hybridization in microarray data and a
      corresponding variational learning method for cross-hybridization compensation,
      GenXHC, that reduces cross-hybridization noise by taking into account multiple
      sources for each mRNA expression level measurement, as well as prior knowledge of
      hybridization similarities between the nucleotide sequences of microarray probes
      and their target cDNAs. RESULTS: The algorithm is applied to a subset of an exon
      resolution genome-wide Agilent microarray data set for chromosome 16 of Mus
      musculus and is found to produce statistically significant reductions in cross
      hybridization noise. The denoised data is found to produce enrichment in multiple
      gene ontology-biological process (GO-BP) functional groups. The algorithm is
      found to outperform robust multi-array analysis, another method for cross
      hybridization compensation.

PMID- 15961462
TI  - Modeling the organization of the WUSCHEL expression domain in the shoot apical
      meristem.
AB  - MOTIVATION: The above-ground tissues of higher plants are generated from a small
      region of cells situated at the plant apex called the shoot apical meristem. An
      important genetic control circuit modulating the size of the Arabidopsis thaliana
      meristem is a feed-back network between the CLAVATA3 and WUSCHEL genes. Although
      the expression patterns for these genes do not overlap, WUSCHEL activity is both
      necessary and sufficient (when expressed ectopically) for the induction of
      CLAVATA3 expression. However, upregulation of CLAVATA3 in conjunction with the
      receptor kinase CLAVATA1 results in the downregulation of WUSCHEL. Despite much
      work, experimental data for this network are incomplete and additional hypotheses
      are needed to explain the spatial locations and dynamics of these expression
      domains. Predictive mathematical models describing the system should provide a
      useful tool for investigating and discriminating among possible hypotheses, by
      determining which hypotheses best explain observed gene expression dynamics.
      RESULTS: We are developing a method using in vivo live confocal microscopy to
      capture quantitative gene expression data and create templates for computational
      models. We present two models accounting for the organization of the WUSCHEL
      expression domain. Our preferred model uses a reaction-diffusion mechanism in
      which an activator induces WUSCHEL expression. This model is able to organize the
      WUSCHEL expression domain. In addition, the model predicts the dynamical
      reorganization seen in experiments where cells, including the WUSCHEL domain, are
      ablated, and it also predicts the spatial expansion of the WUSCHEL domain
      resulting from removal of the CLAVATA3 signal. AVAILABILITY: An extended
      description of the model framework and image processing algorithms can be found
      at http://www.computableplant.org, together with additional results and
      simulation movies. SUPPLEMENTARY INFORMATION: http://www.computableplant.org/ and
      alternatively for a direct link to the page,
      http://computableplant.ics.uci.edu/bti1036 can be accessed.

PMID- 15961463
TI  - Predicting protein-protein interaction by searching evolutionary tree
      automorphism space.
AB  - MOTIVATION: Uncovering the protein-protein interaction network is a fundamental
      step in the quest to understand the molecular machinery of a cell. This motivates
      the search for efficient computational methods for predicting such interactions.
      Among the available predictors are those that are based on the co-evolution
      hypothesis "evolutionary trees of protein families (that are known to interact)
      are expected to have similar topologies". Many of these methods are limited by
      the fact that they can handle only a small number of protein sequences. Also,
      details on evolutionary tree topology are missing as they use similarity matrices
      in lieu of the trees. RESULTS: We introduce MORPH, a new algorithm for predicting
      protein interaction partners between members of two protein families that are
      known to interact. Our approach can also be seen as a new method for searching
      the best superposition of the corresponding evolutionary trees based on tree
      automorphism group. We discuss relevant facts related to the predictability of
      protein-protein interaction based on their co-evolution. When compared with
      related computational approaches, our method reduces the search space by
      approximately 3 x 10(5)-fold and at the same time increases the accuracy of
      predicting correct binding partners.

PMID- 15961464
TI  - An HMM posterior decoder for sequence feature prediction that includes homology
      information.
AB  - MOTIVATION: When predicting sequence features like transmembrane topology, signal
      peptides, coil-coil structures, protein secondary structure or genes, extra
      support can be gained from homologs. RESULTS: We present here a general hidden
      Markov model (HMM) decoding algorithm that combines probabilities for sequence
      features of homologs by considering the average of the posterior label
      probability of each position in a global sequence alignment. The algorithm is an
      extension of the previously described 'optimal accuracy' decoder, allowing
      homology information to be used. It was benchmarked using an HMM for
      transmembrane topology and signal peptide prediction, Phobius. We found that the
      performance was substantially increased when incorporating information from
      homologs. AVAILABILITY: A prediction server for transmembrane topology and signal
      peptides that uses the algorithm is available at
      http://phobius.cgb.ki.se/poly.html. An implementation of the algorithm is
      available on request from the authors.

PMID- 15961465
TI  - Prediction of active sites for protein structures from computed chemical
      properties.
AB  - MOTIVATION: Identification of functional information for a protein from its three
      dimensional (3D) structure is a major challenge in genomics. The power of
      theoretical microscopic titration curves (THEMATICS), when coupled with a
      statistical analysis, provides a method for high-throughput screening for
      identification of catalytic sites and binding sites with high accuracy and
      precision. The method requires only the 3D structure of the query protein as
      input, but it performs as well as other methods that depend on sequence
      alignments and structural similarities.

PMID- 15961466
TI  - High-recall protein entity recognition using a dictionary.
AB  - SUMMARY: Protein name extraction is an important step in mining biological
      literature. We describe two new methods for this task: semiCRFs and dictionary
      HMMs. SemiCRFs are a recently-proposed extension to conditional random fields
      (CRFs) that enables more effective use of dictionary information as features.
      Dictionary HMMs are a technique in which a dictionary is converted to a large HMM
      that recognizes phrases from the dictionary, as well as variations of these
      phrases. Standard training methods for HMMs can be used to learn which variants
      should be recognized. We compared the performance of our new approaches with that
      of Maximum Entropy (MaxEnt) and normal CRFs on three datasets, and improvement
      was obtained for all four methods over the best published results for two of the
      datasets. CRFs and semiCRFs achieved the highest overall performance according to
      the widely-used F-measure, while the dictionary HMMs performed the best at
      finding entities that actually appear in the dictionary-the measure of most
      interest in our intended application. AVAILABILITY: Dictionary HMMs were
      implemented in Java. Algorithms are available through an information extraction
      package MINORTHIRD on http://minorthird.sourceforge.net

PMID- 15961467
TI  - A hidden Markov model for analyzing ChIP-chip experiments on genome tiling arrays
      and its application to p53 binding sequences.
AB  - MOTIVATION: Transcription factors (TFs) regulate gene expression by recognizing
      and binding to specific regulatory regions on the genome, which in higher
      eukaryotes can occur far away from the regulated genes. Recently, Affymetrix
      developed the high-density oligonucleotide arrays that tile all the non
      repetitive sequences of the human genome at 35 bp resolution. This new array
      platform allows for the unbiased mapping of in vivo TF binding sequences (TFBSs)
      using Chromatin ImmunoPrecipitation followed by microarray experiments (ChIP
      chip). The massive dataset generated from these experiments pose great challenges
      for data analysis. RESULTS: We developed a fast, scalable and sensitive method to
      extract TFBSs from ChIP-chip experiments on genome tiling arrays. Our method
      takes advantage of tiling array data from many experiments to normalize and model
      the behavior of each individual probe, and identifies TFBSs using a hidden Markov
      model (HMM). When applied to the data of p53 ChIP-chip experiments from an
      earlier study, our method discovered many new high confidence p53 targets
      including all the regions verified by quantitative PCR. Using a de novo motif
      finding algorithm MDscan, we also recovered the p53 motif from our HMM identified
      p53 target regions. Furthermore, we found substantial p53 motif enrichment in
      these regions comparing with both genomic background and the TFBSs identified
      earlier. Several of the newly identified p53 TFBSs are in the promoter region of
      known genes or associated with previously characterized p53-responsive genes.
      SUPPLEMENTARY INFORMATION: Available at the following URL
      http://genome.dfci.harvard.edu/~xsliu/HMMTiling/index.html.

PMID- 15961468
TI  - Improved detection of DNA motifs using a self-organized clustering of familial
      binding profiles.
AB  - MOTIVATION: One of the limiting factors in deciphering transcriptional regulatory
      networks is the effectiveness of motif-finding software. An emerging avenue for
      improving motif-finding accuracy aims to incorporate generalized binding
      constraints of related transcription factors (TFs), named familial binding
      profiles (FBPs), as priors in motif identification methods. A motif-finder can
      thus be 'biased' towards finding motifs from a particular TF family. However,
      current motif-finders allow only a single FBP to be used as a prior in a given
      motif-finding run. In addition, current FBP construction methods are based on
      manual clustering of position specific scoring matrices (PSSMs) according to the
      known structural properties of the TF proteins. Manual clustering assumes that
      the binding preferences of structurally similar TFs will also be similar. This
      assumption is not true, at least not for some TF families. Automatic PSSM
      clustering methods are thus required for augmenting the usefulness of FBPs.
      RESULTS: A novel method is developed for automatic clustering of PSSM models. The
      resulting FBPs are incorporated into the SOMBRERO motif-finder, significantly
      improving its performance when finding motifs related to those that have been
      incorporated. SOMBRERO is thus the only existing de novo motif-finder that can
      incorporate knowledge of all known PSSMs in a given motif-finding run.
      AVAILABILITY: The methods outlined will be incorporated into the next release of
      SOMBRERO, which is available from http://bioinf.nuigalway.ie/sombrero

PMID- 15961469
TI  - A systematic approach for comprehensive T-cell epitope discovery using peptide
      libraries.
AB  - MOTIVATION: T-cell response to peptides bound on MHC Class I or Class II
      molecules is essential for immune recognition of pathogens. T-cells are activated
      by specific peptide epitopes that are determined within the antigen processing
      pathways and presented on the surface of other cells bound to MHC molecules. To
      determine which part of allergenic or pathogenic proteins can stimulate T-cells
      is important for the treatment of diseases. We sought to take advantage of the
      falling cost of synthetic, screening grade peptides, and devise a comprehensive,
      non-hypothesis-driven screen for T-cell epitopes. We were interested in the study
      of celiac disease (CD) and used the ELISPOT technique to perform a large number
      of T-cell assays. We therefore needed to compensate for the lack of statistical
      data analysis methods for ELISPOT assays. RESULTS: We describe a method to
      comprehensively screen for T-cell epitopes within a family or a group of
      proteins. We have implemented an algorithm to generate a set of unique short
      peptide sequences that incorporate all possible epitopes within a group of
      proteins. T-cell assays were performed in 96-well plates using the ELISPOT assay
      to screen for responses in CD patients against any epitopes in glutens. We
      describe a statistical model to fit the data and an Expectation Maximization
      algorithm to estimate the parameters of interest and analyze the resulting data.
      AVAILABILITY: Implementations of our algorithms in R or Perl are available at
      http://bioinf.wehi.edu.au/folders/immunol.

PMID- 15961470
TI  - High-throughput inference of protein-protein interfaces from unassigned NMR data.
AB  - SUMMARY: We cast the problem of identifying protein-protein interfaces, using
      only unassigned NMR spectra, into a geometric clustering problem. Identifying
      protein-protein interfaces is critical to understanding inter- and intra-cellular
      communication, and NMR allows the study of protein interaction in solution.
      However it is often the case that NMR studies of a protein complex are very time
      consuming, mainly due to the bottleneck in assigning the chemical shifts, even if
      the apo structures of the constituent proteins are known. We study whether it is
      possible, in a high-throughput manner, to identify the interface region of a
      protein complex using only unassigned chemical shifts and residual dipolar
      coupling (RDC) data. We introduce a geometric optimization problem where we must
      cluster the cells in an arrangement on the boundary of a 3-manifold, where the
      arrangement is induced by a spherical quadratic form [corrected] The arrangement
      is induced by a spherical quadratic form, which in turn is parameterized by a
      SO(3)xR2. We show that this formalism derives directly from the physics of RDCs.
      We present an optimal algorithm for this problem that runs in O(n3 log n) time
      for an n-residue protein. We then use this clustering algorithm as a subroutine
      in a practical algorithm for identifying the interface region of a protein
      complex from unassigned NMR data. We present the results of our algorithm on NMR
      data for seven proteins from five protein complexes, and show that our approach
      is useful for high-throughput applications in which we seek to rapidly identify
      the interface region of a protein complex. AVAILABILITY: Contact authors for
      source code.

PMID- 15961472
TI  - Whole-proteome prediction of protein function via graph-theoretic analysis of
      interaction maps.
AB  - MOTIVATION: Determining protein function is one of the most important problems in
      the post-genomic era. For the typical proteome, there are no functional
      annotations for one-third or more of its proteins. Recent high-throughput
      experiments have determined proteome-scale protein physical interaction maps for
      several organisms. These physical interactions are complemented by an abundance
      of data about other types of functional relationships between proteins, including
      genetic interactions, knowledge about co-expression and shared evolutionary
      history. Taken together, these pairwise linkages can be used to build whole
      proteome protein interaction maps. RESULTS: We develop a network-flow based
      algorithm, FunctionalFlow, that exploits the underlying structure of protein
      interaction maps in order to predict protein function. In cross-validation
      testing on the yeast proteome, we show that FunctionalFlow has improved
      performance over previous methods in predicting the function of proteins with few
      (or no) annotated protein neighbors. By comparing several methods that use
      protein interaction maps to predict protein function, we demonstrate that
      FunctionalFlow performs well because it takes advantage of both network topology
      and some measure of locality. Finally, we show that performance can be improved
      substantially as we consider multiple data sources and use them to create
      weighted interaction networks. AVAILABILITY:
      http://compbio.cs.princeton.edu/function

PMID- 15961473
TI  - Computing the P-value of the information content from an alignment of multiple
      sequences.
AB  - MOTIVATION: The efficient and accurate computation of P-values is an essential
      requirement for motif-finding and alignment tools. We show that the approximation
      algorithms used in two popular motif-finding programs, MEME and Consensus, can
      fail to accurately compute the P-value. RESULTS: We present two new algorithms:
      one for the evaluation of the P-values of a range of motif scores, and a faster
      one for the evaluation of the P-value of a single motif score. Both exhibit more
      reliability than existing algorithms, and the latter algorithm is comparable in
      speed to the fastest existing method. AVAILABILITY: The algorithms described in
      this paper are available from http://www.cs.cornell.edu/~keich

PMID- 15961474
TI  - Beyond the clause: extraction of phosphorylation information from medline
      abstracts.
AB  - MOTIVATION: Phosphorylation is an important biochemical reaction that plays a
      critical role in signal transduction pathways and cell-cycle processes. A text
      mining system to extract the phosphorylation relation from the literature is
      reported. The focus of this paper is on the new methods developed and implemented
      to connect and merge pieces of information about phosphorylation mentioned in
      different sentences in the text. The effectiveness and accuracy of the system as
      a whole as well as that of the methods for extraction beyond a clause/sentence is
      evaluated using an independently annotated dataset, the Phospho.ELM database. The
      new methods developed to merge pieces of information from different sentences are
      shown to be effective in significantly raising the recall without much difference
      in precision.

PMID- 15961475
TI  - In silico identification of functional regions in proteins.
AB  - MOTIVATION: In silico prediction of functional regions on protein surfaces, i.e.
      sites of interaction with DNA, ligands, substrates and other proteins, is of
      utmost importance in various applications in the emerging fields of proteomics
      and structural genomics. When a sufficient number of homologs is found, powerful
      prediction schemes can be based on the observation that evolutionarily conserved
      regions are often functionally important, typically, only the principal
      functionally important region of the protein is detected, while secondary
      functional regions with weaker conservation signals are overlooked. Moreover, it
      is challenging to unambiguously identify the boundaries of the functional
      regions. METHODS: We present a new methodology, called PatchFinder, that
      automatically identifies patches of conserved residues that are located in close
      proximity to each other on the protein surface. PatchFinder is based on the
      following steps: (1) Assignment of conservation scores to each amino acid
      position on the protein surface. (2) Assignment of a score to each putative
      patch, based on its likelihood to be functionally important. The patch of maximum
      likelihood is considered to be the main functionally important region, and the
      search is continued for non-overlapping patches of secondary importance. RESULTS:
      We examined the accuracy of the method using the IGPS enzyme, the SH2 domain and
      a benchmark set of 112 proteins. These examples demonstrated that PatchFinder is
      capable of identifying both the main and secondary functional patches.
      AVAILABILITY: The PatchFinder program is available at:
      http://ashtoret.tau.ac.il/~nimrodg/

PMID- 15961476
TI  - Predicting the in vivo signature of human gene regulatory sequences.
AB  - MOTIVATION: In the living cell nucleus, genomic DNA is packaged into chromatin.
      DNA sequences that regulate transcription and other chromosomal processes are
      associated with local disruptions, or 'openings', in chromatin structure caused
      by the cooperative action of regulatory proteins. Such perturbations are
      extremely specific for cis-regulatory elements and occur over short stretches of
      DNA (typically approximately 250 bp). They can be detected experimentally as
      DNaseI hypersensitive sites (HSs) in vivo, though the process is extremely
      laborious and costly. The ability to discriminate DNaseI HSs computationally
      would have a major impact on the annotation and utilization of the human genome.
      RESULTS: We found that a supervised pattern recognition algorithm, trained using
      a set of 280 DNaseI HS and 737 non-HS control sequences from erythroid cells, was
      capable of de novo prediction of HSs across the human genome with surprisingly
      high accuracy determined by prospective in vivo validation. Systematic
      application of this computational approach will greatly facilitate the discovery
      and analysis of functional non-coding elements in the human and other complex
      genomes. AVAILABILITY: Supplementary data is available at
      noble.gs.washington.edu/proj/hs

PMID- 15961477
TI  - Statistics of local multiple alignments.
AB  - SUMMARY: BLAST statistics have been shown to be extremely useful for searching
      for significant similarity hits, for amino acid and nucleotide sequences.
      Although these statistics are well understood for pairwise comparisons, there has
      been little success developing statistical scores for multiple alignments. In
      particular, there is no score for multiple alignment that is well founded and
      treated as a standard. We extend the BLAST theory to multiple alignments.
      Following some simple assumptions, we present and justify a significance score
      for multiple segments of a local multiple alignment. We demonstrate its
      usefulness in distinguishing high and moderate quality multiple alignments from
      low quality ones, with supporting experiments on orthologous vertebrate promoter
      sequences.

PMID- 15961478
TI  - De novo identification of repeat families in large genomes.
AB  - MOTIVATION: De novo repeat family identification is a challenging algorithmic
      problem of great practical importance. As the number of genome sequencing
      projects increases, there is a pressing need to identify the repeat families
      present in large, newly sequenced genomes. We develop a new method for de novo
      identification of repeat families via extension of consensus seeds; our method
      enables a rigorous definition of repeat boundaries, a key issue in repeat
      analysis. RESULTS: Our RepeatScout algorithm is more sensitive and is orders of
      magnitude faster than RECON, the dominant tool for de novo repeat family
      identification in newly sequenced genomes. Using RepeatScout, we estimate that
      approximately 2% of the human genome and 4% of mouse and rat genomes consist of
      previously unannotated repetitive sequence. AVAILABILITY: Source code is
      available for download at http://www
      cse.ucsd.edu/groups/bioinformatics/software.html

PMID- 15961479
TI  - Kernels for small molecules and the prediction of mutagenicity, toxicity and anti
      cancer activity.
AB  - MOTIVATION: Small molecules play a fundamental role in organic chemistry and
      biology. They can be used to probe biological systems and to discover new drugs
      and other useful compounds. As increasing numbers of large datasets of small
      molecules become available, it is necessary to develop computational methods that
      can deal with molecules of variable size and structure and predict their
      physical, chemical and biological properties. RESULTS: Here we develop several
      new classes of kernels for small molecules using their 1D, 2D and 3D
      representations. In 1D, we consider string kernels based on SMILES strings. In
      2D, we introduce several similarity kernels based on conventional or generalized
      fingerprints. Generalized fingerprints are derived by counting in different ways
      subpaths contained in the graph of bonds, using depth-first searches. In 3D, we
      consider similarity measures between histograms of pairwise distances between
      atom classes. These kernels can be computed efficiently and are applied to
      problems of classification and prediction of mutagenicity, toxicity and anti
      cancer activity on three publicly available datasets. The results derived using
      cross-validation methods are state-of-the-art. Tradeoffs between various kernels
      are briefly discussed. AVAILABILITY: Datasets available from
      http://www.igb.uci.edu/servers/servers.html

PMID- 15961480
TI  - RASE: recognition of alternatively spliced exons in C.elegans.
AB  - MOTIVATION: Eukaryotic pre-mRNAs are spliced to form mature mRNA. Pre-mRNA
      alternative splicing greatly increases the complexity of gene expression.
      Estimates show that more than half of the human genes and at least one-third of
      the genes of less complex organisms, such as nematodes or flies, are
      alternatively spliced. In this work, we consider one major form of alternative
      splicing, namely the exclusion of exons from the transcript. It has been shown
      that alternatively spliced exons have certain properties that distinguish them
      from constitutively spliced exons. Although most recent computational studies on
      alternative splicing apply only to exons which are conserved among two species,
      our method only uses information that is available to the splicing machinery,
      i.e. the DNA sequence itself. We employ advanced machine learning techniques in
      order to answer the following two questions: (1) Is a certain exon alternatively
      spliced? (2) How can we identify yet unidentified exons within known introns?
      RESULTS: We designed a support vector machine (SVM) kernel well suited for the
      task of classifying sequences with motifs having positional preferences. In order
      to solve the task (1), we combine the kernel with additional local sequence
      information, such as lengths of the exon and the flanking introns. The resulting
      SVM-based classifier achieves a true positive rate of 48.5% at a false positive
      rate of 1%. By scanning over single EST confirmed exons we identified 215
      potential alternatively spliced exons. For 10 randomly selected such exons we
      successfully performed biological verification experiments and confirmed three
      novel alternatively spliced exons. To answer question (2), we additionally used
      SVM-based predictions to recognize acceptor and donor splice sites. Combined with
      the above mentioned features we were able to identify 85.2% of skipped exons
      within known introns at a false positive rate of 1%. AVAILABILITY: Datasets,
      model selection results, our predictions and additional experimental results are
      available at http://www.fml.tuebingen.mpg.de/~raetsch/RASE SUPPLEMENTARY
      INFORMATION: http://www.fml.tuebingen.mpg.de/raetsch/RASE.

PMID- 15961481
TI  - Families of membranous proteins can be characterized by the amino acid
      composition of their transmembrane domains.
AB  - SUMMARY: In eukaryotes, membranous proteins account for 20-30% of the proteome.
      Most of these proteins contain one or more transmembrane (TM) domains. These are
      short segments that transverse the bilayer lipid membrane. Various properties of
      the TM domains, such as their number, their topology and their arrangement within
      the membrane, are closely related to the protein's cellular functions. The
      properties of the TM domains also determine the cellular targeting and
      localization of these proteins. It is not known, however, whether the information
      encoded by TM domains suffices for the purpose of classifying proteins into their
      functional families. This is the question we address here. We introduce an
      algorithm that creates a profile of each functional family of membranous proteins
      based only on the amino acid composition of their TM domains. This is
      complemented by a classifier program for each such family (to determine whether a
      given protein belongs to it or not). We find that in most instances TM domains
      contain enough information to allow an accurate discrimination of approximately
      80% sensitivity and approximately 90% specificity among unrelated polytopic
      functional families with the same number of TM domains. SUPPLEMENTARY
      INFORMATION: Available at www.protonet.cs.huji.ac.il/TM/

PMID- 15961482
TI  - Kernel methods for predicting protein-protein interactions.
AB  - MOTIVATION: Despite advances in high-throughput methods for discovering protein
      protein interactions, the interaction networks of even well-studied model
      organisms are sketchy at best, highlighting the continued need for computational
      methods to help direct experimentalists in the search for novel interactions.
      RESULTS: We present a kernel method for predicting protein-protein interactions
      using a combination of data sources, including protein sequences, Gene Ontology
      annotations, local properties of the network, and homologous interactions in
      other species. Whereas protein kernels proposed in the literature provide a
      similarity between single proteins, prediction of interactions requires a kernel
      between pairs of proteins. We propose a pairwise kernel that converts a kernel
      between single proteins into a kernel between pairs of proteins, and we
      illustrate the kernel's effectiveness in conjunction with a support vector
      machine classifier. Furthermore, we obtain improved performance by combining
      several sequence-based kernels based on k-mer frequency, motif and domain content
      and by further augmenting the pairwise sequence kernel with features that are
      based on other sources of data. We apply our method to predict physical
      interactions in yeast using data from the BIND database. At a false positive rate
      of 1% the classifier retrieves close to 80% of a set of trusted interactions. We
      thus demonstrate the ability of our method to make accurate predictions despite
      the sizeable fraction of false positives that are known to exist in interaction
      databases. AVAILABILITY: The classification experiments were performed using PyML
      available at http://pyml.sourceforge.net. Data are available at:
      http://noble.gs.washington.edu/proj/sppi.

PMID- 15961483
TI  - A motif-based framework for recognizing sequence families.
AB  - MOTIVATION: Many signals in biological sequences are based on the presence or
      absence of base signals and their spatial combinations. One of the best known
      examples of this is the signal identifying a core promoter--the site at which the
      basal transcription machinery starts the transcription of a gene. Our goal is a
      fully automatic pattern recognition system for a family of sequences, which
      simultaneously discovers the base signals, their spatial relationships and a
      classifier based upon them. RESULTS: In this paper we present a general method
      for characterizing a set of sequences by their recurrent motifs. Our approach
      relies on novel probabilistic models for DNA binding sites and modules of binding
      sites, on algorithms to study them from the data and on a support vector machine
      that uses the models studied to classify a set of sequences. We demonstrate the
      applicability of our approach to diverse instances, ranging from families of
      promoter sequences to a dataset of intronic sequences flanking alternatively
      spliced exons. On a core promoter dataset our results are comparable with the
      state-of-the-art McPromoter. On a dataset of alternatively spliced exons we
      outperform a previous approach. We also achieve high success rates in recognizing
      cell cycle regulated genes. These results demonstrate that a fully automatic
      pattern recognition algorithm can meet or exceed the performance of hand-crafted
      approaches. AVAILABILITY: The software and datasets are available from the
      authors upon request.

PMID- 15961484
TI  - Search for folding nuclei in native protein structures.
AB  - The problem of finding folding nuclei (a set of native contacts that play an
      important role in folding) along with identifying folding pathways (a time
      ordered sequence of folding events) of proteins is one of the most important
      problems in protein chemistry. Here we propose a novel and simple approach to
      address this problem as follows: given the topology of the native state, identify
      native contacts that form folding nuclei based on a graph-theoretical approach
      that considers effective contact order (effective loop closure) as its objective
      function. MOTIVATION: A number of computational methods for the prediction of
      folding nuclei already exists in the literature, but most of them rely on
      restrictive assumptions about the nature of nuclei or the process of folding. Our
      motivation is to develop a simple, efficient and robust algorithm to find an
      ensemble of pathways with the lowest effective contact order and to identify
      contacts that are crucial for folding. RESULTS: Our approach is different from
      the previously used methods in that it uses efficient graph algorithms and does
      not formulate restrictive assumptions about folding nuclei. Our predictions
      provide more details concerning the protein folding pathway than most other
      methods in the literature. We demonstrate the success of our approach by
      predicting folding nuclei for a dataset of proteins for which experimental
      kinetic data is available. We show that our method compares favourably with other
      methods in the literature and that its results agree with experimental results.
      AVAILABILITY: The executable for the proposed algorithm is available at
      http://www.cs.ubc.ca/~/foldingnuclei.html

PMID- 15961485
TI  - Mining ChIP-chip data for transcription factor and cofactor binding sites.
AB  - MOTIVATION: Identification of single motifs and motif pairs that can be used to
      predict transcription factor localization in ChIP-chip data, and gene expression
      in tissue-specific microarray data. RESULTS: We describe methodology to identify
      de novo individual and interacting pairs of binding site motifs from ChIP-chip
      data, using an algorithm that integrates localization data directly into the
      motif discovery process. We combine matrix-enumeration based motif discovery with
      multivariate regression to evaluate candidate motifs and identify motif
      interactions. When applied to the HNF localization data in liver and pancreatic
      islets, our methods produce motifs that are either novel or improved known
      motifs. All motif pairs identified to predict localization are further evaluated
      according to how well they predict expression in liver and islets and according
      to how conserved are the relative positions of their occurrences. We find that
      interaction models of HNF1 and CDP motifs provide excellent prediction of both
      HNF1 localization and gene expression in liver. Our results demonstrate that ChIP
      chip data can be used to identify interacting binding site motifs. AVAILABILITY:
      Motif discovery programs and analysis tools are available on request from the
      authors.

PMID- 15961486
TI  - Efficient computation of close lower and upper bounds on the minimum number of
      recombinations in biological sequence evolution.
AB  - MOTIVATION: We are interested in studying the evolution of DNA single nucleotide
      polymorphism sequences which have undergone (meiotic) recombination. For a given
      set of sequences, computing the minimum number of recombinations needed to
      explain the sequences (with one mutation per site) is a standard question of
      interest, but it has been shown to be NP-hard, and previous algorithms that
      compute it exactly work either only on very small datasets or on problems with
      special structure. RESULTS: In this paper, we present efficient, practical
      methods for computing both upper and lower bounds on the minimum number of needed
      recombinations, and for constructing evolutionary histories that explain the
      input sequences. We study in detail the efficiency and accuracy of these
      algorithms on both simulated and real data sets. The algorithms produce very
      close upper and lower bounds, which match exactly in a surprisingly wide range of
      data. Thus, with the use of new, very effective lower bounding methods and an
      efficient algorithm for computing upper bounds, this approach allows the
      efficient, exact computation of the minimum number of needed recombinations, with
      high frequency in a large range of data. When upper and lower bounds match,
      evolutionary histories found by our algorithm correspond to the most parsimonious
      histories. AVAILABILITY: HapBound and SHRUB, programs implementing the new
      algorithms discussed in this paper, are available at
      http://wwwcsif.cs.ucdavis.edu/~gusfield/lu.html

PMID- 15961487
TI  - Robust classification modeling on microarray data using misclassification
      penalized posterior.
AB  - MOTIVATION: Genome-wide microarray data are often used in challenging
      classification problems of clinically relevant subtypes of human diseases.
      However, the identification of a parsimonious robust prediction model that
      performs consistently well on future independent data has not been successful due
      to the biased model selection from an extremely large number of candidate models
      during the classification model search and construction. Furthermore, common
      criteria of prediction model performance, such as classification error rates, do
      not provide a sensitive measure for evaluating performance of such astronomic
      competing models. Also, even though several different classification approaches
      have been utilized to tackle such classification problems, no direct comparison
      on these methods have been made. RESULTS: We introduce a novel measure for
      assessing the performance of a prediction model, the misclassification-penalized
      posterior (MiPP), the sum of the posterior classification probabilities penalized
      by the number of incorrectly classified samples. Using MiPP, we implement a
      forward step-wise cross-validated procedure to find our optimal prediction models
      with different numbers of features on a training set. Our final robust
      classification model and its dimension are determined based on a completely
      independent test dataset. This MiPP-based classification modeling approach
      enables us to identify the most parsimonious robust prediction models only with
      two or three features on well-known microarray datasets. These models show
      superior performance to other models in the literature that often have more than
      40-100 features in their model construction. AVAILABILITY: Our MiPP software
      program is available at the Bioconductor website (http://www.bioconductor.org).

PMID- 15961488
TI  - Automated interpretation of MS/MS spectra of oligosaccharides.
AB  - MOTIVATION: The emerging glycomics and glycoproteomics projects aim to
      characterize all forms of glycoproteins in different tissues and organisms.
      Tandem mass spectrometry (MS/MS) is the key experimental methodology for high
      throughput glycan identification and characterization. Fragmentation of glycans
      from high energy collision-induced dissociation generates ions from glycosidic as
      well as internal cleavages. The cross-ring ions resulting from internal cleavages
      provide additional information that is important to reveal the type of linkage
      between monosaccharides. This information, however, is not incorporated into the
      current programs for analyzing glycan mass spectra. As a result, they can rarely
      distinguish from the mass spectra isomeric oligosaccharides, which have the same
      saccharide composition but different types of sequences, branches or linkages.
      RESULTS: In this paper, we describe a novel algorithm for glycan characterization
      using MS/MS. This algorithm consists of three steps. First, we develop a scoring
      scheme to identify potential bond linkages between monosaccharides, based on the
      appearance pattern of cross-ring ions. Next, we use a dynamic programming
      algorithm to determine the most probable oligosaccharide structures from the mass
      spectrum. Finally, we re-evaluate these oligosaccharide structures, taking into
      account the double fragmentation ions. We also show the preliminary results of
      testing our algorithm on several MS/MS spectra of oligosaccharides. AVAILABILITY:
      The program GLYCH is available upon request from the authors.

PMID- 15961489
TI  - Alignments anchored on genomic landmarks can aid in the identification of
      regulatory elements.
AB  - MOTIVATION: The transcription start site (TSS) has been located for an increasing
      number of genes across several organisms. Statistical tests have shown that some
      cis-acting regulatory elements have positional preferences with respect to the
      TSS, but few strategies have emerged for locating elements by their positional
      preferences. This paper elaborates such a strategy. First, we align promoter
      regions without gaps, anchoring the alignment on each promoter's TSS. Second, we
      apply a novel word-specific mask. Third, we apply a clustering test related to
      gapless BLAST statistics. The test examines whether any specific word is placed
      unusually consistently with respect to the TSS. Finally, our program A-GLAM, an
      extension of the GLAM program, uses significant word positions as new 'anchors'
      to realign the sequences. A Gibbs sampling algorithm then locates putative cis
      acting regulatory elements. Usually, Gibbs sampling requires a preliminary
      masking step, to avoid convergence onto a dominant but uninteresting signal from
      a DNA repeat. However, since the positional anchors focus A-GLAM on the motif of
      interest, masking DNA repeats during Gibbs sampling becomes unnecessary. RESULTS:
      In a set of human DNA sequences with experimentally characterized TSSs, the
      placement of 791 octonucleotide words was unusually consistent (multiple test
      corrected P < 0.05). Alignments anchored on these words sometimes located
      statistically significant motifs inaccessible to GLAM or AlignACE. AVAILABILITY:
      The A-GLAM program and a list of statistically significant words are available at
      ftp://ftp.ncbi.nih.gov/pub/spouge/papers/archive/AGLAM/.

PMID- 15961490
TI  - How old is your fold?
AB  - MOTIVATION: At present there exists no age estimate for the different protein
      structures found in nature. It has become clear from occurrence studies that
      different folds arose at different points in evolutionary time. An estimation of
      the age of different folds would be a starting point for many investigations into
      protein structure evolution: how we arrived at the set of folds we see today. It
      would also be a powerful tool in protein structure classification allowing us to
      reassess the available hierarchical methods and perhaps suggest improvements.
      RESULTS: We have created the first relative age estimation technique for protein
      folds. Our method is based on constructing parsimonious scenarios, which can
      describe occurrence patterns in a phylogeny of species. The ages presented are
      shown to be robust to the different trees or data types used for their
      generation. They show correlations with other previously used protein age
      estimators, but appear to be far more discriminating than any previously
      suggested technique. The age estimates given are not absolutes but they already
      offer intriguing insights, like the very different age patterns of alpha/beta
      folds compared with small folds. The alpha/beta folds appear on average to be far
      older than their small fold counterparts. AVAILABILITY: Example trees and
      additional material are available at http://www.stats.ox.ac.uk/~abeln/foldage
      SUPPLEMENTARY INFORMATION: http://www.stats.ox.ac.uk/~abeln/foldage.

PMID- 15961491
TI  - Experimental design for three-color and four-color gene expression microarrays.
AB  - MOTIVATION: Three-color microarrays, compared with two-color microarrays, can
      increase design efficiency and power to detect differential expression without
      additional samples and arrays. Furthermore, three-color microarray technology is
      currently available at a reasonable cost. Despite the potential advantages, clear
      guidelines for designing and analyzing three-color experiments do not exist.
      RESULTS: We propose a three- and a four-color cyclic design (loop) and a
      complementary graphical representation to help design experiments that are
      balanced, efficient and robust to hybridization failures. In theory, three-color
      loop designs are more efficient than two-color loop designs. Experiments using
      both two- and three-color platforms were performed in parallel and their outputs
      were analyzed using linear mixed model analysis in R/MAANOVA. These results
      demonstrate that three-color experiments using the same number of samples (and
      fewer arrays) will perform as efficiently as two-color experiments. The improved
      efficiency of the design is somewhat offset by a reduced dynamic range and
      increased variability in the three-color experimental system. This result
      suggests that, with minor technological improvements, three-color microarrays
      using loop designs could detect differential expression more efficiently than two
      color loop designs. AVAILABILITY:
      http://www.jax.org/staff/churchill/labsite/software SUPPLEMENTARY INFORMATION:
      Multicolor cyclic design construction methods and examples along with additional
      results of the experiment are provided at
      http://www.jax.org/staff/churchill/labsite/pubs/yong.

PMID- 15961492
TI  - Supervised enzyme network inference from the integration of genomic data and
      chemical information.
AB  - MOTIVATION: The metabolic network is an important biological network which
      relates enzyme proteins and chemical compounds. A large number of metabolic
      pathways remain unknown nowadays, and many enzymes are missing even in known
      metabolic pathways. There is, therefore, an incentive to develop methods to
      reconstruct the unknown parts of the metabolic network and to identify genes
      coding for missing enzymes. RESULTS: This paper presents new methods to infer
      enzyme networks from the integration of multiple genomic data and chemical
      information, in the framework of supervised graph inference. The originality of
      the methods is the introduction of chemical compatibility as a constraint for
      refining the network predicted by the network inference engine. The chemical
      compatibility between two enzymes is obtained automatically from the information
      encoded by their Enzyme Commission (EC) numbers. The proposed methods are tested
      and compared on their ability to infer the enzyme network of the yeast
      Saccharomyces cerevisiae from four datasets for enzymes with assigned EC numbers:
      gene expression data, protein localization data, phylogenetic profiles and
      chemical compatibility information. It is shown that the prediction accuracy of
      the network reconstruction consistently improves owing to the introduction of
      chemical constraints, the use of a supervised approach and the weighted
      integration of multiple datasets. Finally, we conduct a comprehensive prediction
      of a global enzyme network consisting of all enzyme candidate proteins of the
      yeast to obtain new biological findings. AVAILABILITY: Softwares are available
      upon request.

PMID- 15961493
TI  - Protein function prediction via graph kernels.
AB  - MOTIVATION: Computational approaches to protein function prediction infer protein
      function by finding proteins with similar sequence, structure, surface clefts,
      chemical properties, amino acid motifs, interaction partners or phylogenetic
      profiles. We present a new approach that combines sequential, structural and
      chemical information into one graph model of proteins. We predict functional
      class membership of enzymes and non-enzymes using graph kernels and support
      vector machine classification on these protein graphs. RESULTS: Our graph model,
      derivable from protein sequence and structure only, is competitive with vector
      models that require additional protein information, such as the size of surface
      pockets. If we include this extra information into our graph model, our
      classifier yields significantly higher accuracy levels than the vector models.
      Hyperkernels allow us to select and to optimally combine the most relevant node
      attributes in our protein graphs. We have laid the foundation for a protein
      function prediction system that integrates protein information from various
      sources efficiently and effectively. AVAILABILITY: More information available via
      www.dbs.ifi.lmu.de/Mitarbeiter/borgwardt.html.

PMID- 15961494
TI  - Automatic detection of subsystem/pathway variants in genome analysis.
AB  - MOTIVATION: Proteins work together in pathways and networks, collectively
      comprising the cellular machinery. A subsystem (a generalization of pathway
      concept) is a group of related functional roles (such as enzymes) jointly
      involved in a specific aspect of the cellular machinery. Subsystems provide a
      natural framework for comparative genome analysis and functional annotation. A
      subsystem may be implemented in a number of different functional variants in
      individual species. In order to reliably project functional assignments across
      multiple genomes, we have to be able to identify the variants implemented in each
      genome. The analysis of such variants across diverse species is an interesting
      problem by itself and may provide new evolutionary insights. However, no
      computational techniques are presently available for an automated detection and
      analysis of subsystem variants. RESULTS: Here we formulate the subsystem variant
      detection problem as finding the minimum number of subgraphs of a subsystem,
      which is represented as a graph, and solve the optimization problem by integer
      programming approach. The performance of our method was tested on subsystems
      encoded in the SEED, a genomic integration platform developed by the Fellowship
      for Interpretation of Genomes as a component of a large-scale effort on
      comparative analysis and annotation of multiple diverse genomes. Here we
      illustrate the results obtained for two expert-encoded subsystems of the
      biosynthesis of Coenzyme A and FMN/FAD cofactors. Applications of variant
      detection, to support genomic annotations and to assess divergence of species,
      are briefly discussed in the context of these universally conserved and essential
      metabolic subsystems. SUPPLEMENTARY INFORMATION: The details of the variant
      detection results are available at http://ffas.burnham.org/svar/supp.html.

PMID- 15961495
TI  - Bayesian neural network approaches to ovarian cancer identification from high
      resolution mass spectrometry data.
AB  - MOTIVATION: The classification of high-dimensional data is always a challenge to
      statistical machine learning. We propose a novel method named shallow feature
      selection that assigns each feature a probability of being selected based on the
      structure of training data itself. Independent of particular classifiers, the
      high dimension of biodata can be fleetly reduced to an applicable case for
      consequential processing. Moreover, to improve both efficiency and performance of
      classification, these prior probabilities are further used to specify the
      distributions of top-level hyperparameters in hierarchical models of Bayesian
      neural network (BNN), as well as the parameters in Gaussian process models.
      RESULTS: Three BNN approaches were derived and then applied to identify ovarian
      cancer from NCI's high-resolution mass spectrometry data, which yielded an
      excellent performance in 1000 independent k-fold cross validations (k =
      2,...,10). For instance, indices of average sensitivity and specificity of 98.56
      and 98.42%, respectively, were achieved in the 2-fold cross validations.
      Furthermore, only one control and one cancer were misclassified in the leave-one
      out cross validation. Some other popular classifiers were also tested for
      comparison. AVAILABILITY: The programs implemented in MatLab, R and Neal's
      fbm.2004-11-10.

PMID- 15961497
TI  - Reversal distance for partially ordered genomes.
AB  - MOTIVATION: The total order of the genes or markers on a chromosome inherent in
      its representation as a signed per-mutation must often be weakened to a partial
      order in the case of real data. This is due to lack of resolution (where several
      genes are mapped to the same chromosomal position) to missing data from some of
      the datasets used to compile a gene order, and to conflicts between these
      datasets. The available genome rearrangement algorithms, however, require total
      orders as input. A more general approach is needed to handle rearrangements of
      gene partial orders. RESULTS: We formalize the uncertainty in gene order data by
      representing a chromosome from each genome as a partial order, summarized by a
      directed acyclic graph (DAG). The rearrangement problem is then to infer a
      minimal sequence of reversals for transforming any topological sort of one DAG to
      any one of the other DAG. Each topological sort represents a possible
      linearization compatible with all the datasets on the chromosome. The set of all
      possible topological sorts is embedded in each DAG by appropriately augmenting
      the edge set, so that it becomes a general directed graph (DG). The DGs
      representing chromosomes of two genomes are combined to produce a bicoloured
      graph from which we extract a maximal decomposition into alternating coloured
      cycles, and from which, in turn, an optimal sequence of reversals can usually be
      identified. We test this approach on simulated incomplete comparative maps and on
      cereal chromosomal maps drawn from the Gramene browser.

PMID- 15961496
TI  - Classifying noisy protein sequence data: a case study of immunoglobulin light
      chains.
AB  - SUMMARY: The classification of protein sequences obtained from patients with
      various immunoglobulin-related conformational diseases may provide insight into
      structural correlates of pathogenicity. However, clinical data are very sparse
      and, in the case of antibody-related proteins, the collected sequences have large
      variability with only a small subset of variations relevant to the protein
      pathogenicity (function). On this basis, these sequences represent a model system
      for development of strategies to recognize the small subset of function
      determining variations among the much larger number of primary structure
      diversifications introduced during evolution. Under such conditions, most protein
      classification algorithms have limited accuracy. To address this problem, we
      propose a support vector machine (SVM)-based classifier that combines sequence
      and 3D structural averaging information. Each amino acid in the sequence is
      represented by a set of six physicochemical properties: hydrophobicity,
      hydrophilicity, volume, surface area, bulkiness and refractivity. Each position
      in the sequence is described by the properties of the amino acid at that position
      and the properties of its neighbors in 3D space or in the sequence. A structure
      template is selected to determine neighbors in 3D space and a window size is used
      to determine the neighbors in the sequence. The test data consist of 209 proteins
      of human antibody immunoglobulin light chains, each represented by aligned
      sequences of 120 amino acids. The methodology is applied to the classification of
      protein sequences collected from patients with and without amyloidosis, and
      indicates that the proposed modified classifiers are more robust to sequence
      variability than standard SVM classifiers, improving classification error between
      5 and 25% and sensitivity between 9 and 17%. The classification results might
      also suggest possible mechanisms for the propensity of immunoglobulin light
      chains to amyloid formation.

PMID- 15961499
TI  - ExonHunter: a comprehensive approach to gene finding.
AB  - MOTIVATION: We present ExonHunter, a new and comprehensive gene finding system
      that outperforms existing systems and features several new ideas and approaches.
      Our system combines numerous sources of information (genomic sequences, expressed
      sequence tags and protein databases of related species) into a gene finder based
      on a hidden Markov model in a novel and systematic way. In our framework, various
      sources of information are expressed as partial probabilistic statements about
      positions in the sequence and their annotation. We then combine these into the
      final prediction via a quadratic programming method, which we show to be an
      extension of existing methods. Allowing only partial statements is key to our
      transparent handling of missing information and coping with the heterogeneous
      character of individual sources of information. In addition, we give a new method
      for modeling the length distribution of intergenic regions in hidden Markov
      models. RESULTS: On a commonly used test set, ExonHunter performs significantly
      better than the existing gene finders ROSETTA, SLAM and TWINSCAN, with more than
      two-thirds of genes predicted completely correctly. AVAILABILITY: Supplementary
      material available at http://www.bioinformatics.uwaterloo.ca/supplements/05eh/

PMID- 15961500
TI  - Improving protein structure prediction with model-based search.
AB  - MOTIVATION: De novo protein structure prediction can be formulated as search in a
      high-dimensional space. One of the most frequently used computational tools to
      solve such search problems is the Monte Carlo method. We present a novel search
      technique, called model-based search. This method samples the high-dimensional
      search space to build an approximate model of the underlying function. This model
      is incrementally refined in areas of interest, whereas areas that are not of
      interest are excluded from further exploration. Model-based search derives its
      efficiency from the fact that the information obtained during the exploration of
      the search space is used to guide further exploration. In contrast, Monte Carlo
      based techniques lack memory and exploration is performed based on random walks,
      ignoring the information obtained in previous steps. RESULTS: Model-based search
      is applied to protein structure prediction, where search is employed to find the
      global minimum of the protein's energy landscape. We show that model-based search
      uses computational resources more efficiently to find lower-energy conformations
      of proteins than one of the leading protein structure prediction methods, which
      relies on a tailored Monte Carlo method to perform a search. The performance
      improvements become more pronounced as the dimensionality of the search problem
      increases. We argue that model-based search will enable more accurate protein
      structure prediction than was previously possible. Furthermore, we believe that
      similar performance improvements can be expected in other problems that are
      currently solved using Monte Carlo-based search methods. AVAILABILITY: An
      implementation of model-based search can be obtained by contacting the authors.

PMID- 15961501
TI  - Three-stage prediction of protein beta-sheets by neural networks, alignments and
      graph algorithms.
AB  - MOTIVATION: Protein beta-sheets play a fundamental role in protein structure,
      function, evolution and bioengineering. Accurate prediction and assembly of
      protein beta-sheets, however, remains challenging because protein beta-sheets
      require formation of hydrogen bonds between linearly distant residues. Previous
      approaches for predicting beta-sheet topological features, such as beta-strand
      alignments, in general have not exploited the global covariation and constraints
      characteristic of beta-sheet architectures. RESULTS: We propose a modular
      approach to the problem of predicting/assembling protein beta-sheets in a chain
      by integrating both local and global constraints in three steps. The first step
      uses recursive neural networks to predict pairing probabilities for all pairs of
      interstrand beta-residues from profile, secondary structure and solvent
      accessibility information. The second step applies dynamic programming techniques
      to these probabilities to derive binding pseudoenergies and optimal alignments
      between all pairs of beta-strands. Finally, the third step uses graph matching
      algorithms to predict the beta-sheet architecture of the protein by optimizing
      the global pseudoenergy while enforcing strong global beta-strand pairing
      constraints. The approach is evaluated using cross-validation methods on a large
      non-homologous dataset and yields significant improvements over previous methods.
      AVAILABILITY: http://www.igb.uci.edu/servers/psss.html.

PMID- 15961503
TI  - Conservative extraction of over-represented extensible motifs.
AB  - MOTIVATION: The discovery of motifs in biosequences is frequently torn between
      the rigidity of the model on the one hand and the abundance of candidates on the
      other. In particular, the variety of motifs described by strings that include
      'don't care' (dot) patterns escalates exponentially with the length of the motif,
      and this gets only worse if a dot is allowed to stretch up to some prescribed
      maximum length. This circumstance tends to generate daunting computational
      burdens, and often gives rise to tables that are impossible to visualize and
      digest. This is unfortunate, as it seems to preclude precisely those massive
      analyses that have become conceivable with the increasing availability of massive
      genomic and protein data. Although a part of the problem is endemic, another part
      of it seems rooted in the various characterizations offered for the notion of a
      motif, that are typically based either on syntax or on statistics alone. It seems
      worthwhile to consider alternatives that result from a prudent combination of
      these two aspects in the model. RESULTS: We introduce and study a notion of
      extensible motif in a sequence which tightly combines the structure of the motif
      pattern, as described by its syntactic specification, with the statistical
      measure of its occurrence count. We show that a combination of appropriate
      saturation conditions (expressed in terms of minimum number of dots compatible
      with a given list of occurrences) and the monotonicity of probabilistic scores
      over regions of constant frequency afford us significant parsimony in the
      generation and testing of candidate over-represented motifs. The merits of the
      method are documented by the results obtained in implementation, which
      specifically targeted protein sequence families. In all cases tested, the motif
      reported in PROSITE as the most important in terms of functional/structural
      relevance emerges among the top 30 extensible motifs returned by our algorithm,
      often right at the top. Of equal importance seems the fact that the sets of all
      surprising motifs returned in each experiment are extracted faster and come in
      much more manageable sizes than would be obtained in the absence of saturation
      constrains. AVAILABILITY: This software will be available for use with the suite
      of tools at www.research.ibm.com/bioinformatics.

PMID- 15961502
TI  - YeastHub: a semantic web use case for integrating data in the life sciences
      domain.
AB  - MOTIVATION: As the semantic web technology is maturing and the need for life
      sciences data integration over the web is growing, it is important to explore how
      data integration needs can be addressed by the semantic web. The main problem
      that we face in data integration is a lack of widely-accepted standards for
      expressing the syntax and semantics of the data. We address this problem by
      exploring the use of semantic web technologies-including resource description
      framework (RDF), RDF site summary (RSS), relational-database-to-RDF mapping
      (D2RQ) and native RDF data repository-to represent, store and query both metadata
      and data across life sciences datasets. RESULTS: As many biological datasets are
      presently available in tabular format, we introduce an RDF structure into which
      they can be converted. Also, we develop a prototype web-based application called
      YeastHub that demonstrates how a life sciences data warehouse can be built using
      a native RDF data store (Sesame). This data warehouse allows integration of
      different types of yeast genome data provided by different resources in different
      formats including the tabular and RDF formats. Once the data are loaded into the
      data warehouse, RDF-based queries can be formulated to retrieve and query the
      data in an integrated fashion. AVAILABILITY: The YeastHub website is accessible
      via the following URL: http://yeasthub.gersteinlab.org.

PMID- 15961504
TI  - Maximum likelihood of evolutionary trees: hardness and approximation.
AB  - MOTIVATION: Maximum likelihood (ML) is an increasingly popular optimality
      criterion for selecting evolutionary trees. Yet the computational complexity of
      ML was open for over 20 years, and only recently resolved by the authors for the
      Jukes-Cantor model of substitution and its generalizations. It was proved that
      reconstructing the ML tree is computationally intractable (NP-hard). In this work
      we explore three directions, which extend that result. RESULTS: (1) We show that
      ML under the assumption of molecular clock is still computationally intractable
      (NP-hard). (2) We show that not only is it computationally intractable to find
      the exact ML tree, even approximating the logarithm of the ML for any
      multiplicative factor smaller than 1.00175 is computationally intractable. (3) We
      develop an algorithm for approximating log-likelihood under the condition that
      the input sequences are sparse. It employs any approximation algorithm for
      parsimony, and asymptotically achieves the same approximation ratio. We note that
      ML reconstruction for sparse inputs is still hard under this condition, and
      furthermore many real datasets satisfy it.

PMID- 15961505
TI  - Sumoylation of the estrogen receptor alpha hinge region regulates its
      transcriptional activity.
AB  - The steroid hormone 17beta-estradiol (estrogen) plays a significant role in the
      normal physiology of the mammary gland and breast cancer development primarily
      through binding to its receptor, the estrogen receptor alpha (ERalpha). ERalpha
      is a nuclear transcription factor undergoing different types of posttranslational
      modifications, i.e. phosphorylation, acetylation, and ubiquitination, which
      regulate its transcriptional activation and/or stability. Here we identify
      ERalpha as a new target for small ubiquitin-like modifier (SUMO)-1 modification
      in intact cells and in vitro. Moreover, ERalpha sumoylation occurs strictly in
      the presence of hormone. SUMO-1 appears to regulate ERalpha-dependent
      transcription. Using a series of mutants, we demonstrated that ERalpha is
      sumoylated at conserved lysine residues within the hinge region. Mutations that
      prevented SUMO modification impaired ERalpha-induced transcription without
      influencing ERalpha cellular localization. In addition to identifying protein
      inhibitor of activated signal transducer and activator of transcription (PIAS)1
      and PIAS3 as E3 ligases for ERalpha, we also found that PIAS1 and PIAS3, as well
      as Ubc9, modulated ERalpha-dependent transcription independently from their SUMO
      1 conjugation activity. These findings identify sumoylation as a new mechanism
      modulating ERalpha-dependent cellular response and provide a link between the
      SUMO and estrogen pathways.

PMID- 15961506
TI  - The nuclear xenobiotic receptor pregnane X receptor: recent insights and new
      challenges.
AB  - The nuclear receptor pregnane X receptor (PXR) plays a key but structurally
      enigmatic role in human biology. This ligand-regulated transcription factor
      responds to a diverse array of chemically distinct ligands, including many
      endogenous compounds and clinical drugs, and regulates the expression of a
      critical set of protective gene products involved in xenobiotic and endobiotic
      metabolism. The structural basis of this receptor's remarkable and unique
      promiscuity is just now coming into focus. We examine the importance of mobile
      regions novel to the nuclear receptor ligand-binding domain fold in the ability
      of PXR to respond to a variety of small and large agonists. We also review the
      functional roles played by PXR in numerous biological pathways and outline
      emerging areas for the future examination of this key nuclear xenobiotic
      receptor.

PMID- 15961507
TI  - Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein
      lipase.
AB  - Activation of protein kinase A by catecholamines inhibits lipoprotein lipase
      (LPL) activity through the elaboration of an RNA binding complex, which inhibits
      LPL translation by binding to the 3'-untranslated region of the LPL mRNA. To
      better define this process, we reconstituted the inhibitory RNA binding complex
      in vitro and demonstrated that the K homology (KH) domain of A kinase anchor
      protein (AKAP) 121/149 plays a vital role in the inhibition of LPL translation.
      Inhibition of LPL translation occurred in vitro only when the Calpha subunit, R
      subunit, and AKAP 149 were present. Using different glutathione-S-transferase
      fusion proteins of AKAP 149, sequences containing the KH domain were required for
      inhibition of LPL translation, and the inhibition of AKAP 121 expression in 3T3
      F442A adipocytes with short interfering RNA resulted in loss of epinephrine
      mediated translation inhibition. After epinephrine injection into mice, LPL
      activity was inhibited in white adipose tissue but not in brown adipose tissue
      (BAT) or muscle. LPL activity and synthetic rate were inhibited in vitro by the
      addition of epinephrine to 3T3-F442A adipocytes, but there was no effect in L6
      muscle cells and cultures of brown adipocytes. Corresponding with these
      differences in LPL translation, AKAP 121 protein and mRNA were abundantly
      expressed in mouse white adipose tissue, but was either very low or undetectable
      in BAT and muscle. Thus, AKAP 121/149 contains a KH region that is essential to
      the translation inhibition of LPL in response to epinephrine. BAT and muscle do
      not express significant AKAP 121/149, and this likely explains some of the tissue
      specific differences in LPL regulation.

PMID- 15961508
TI  - Transcript profiling of immediate early genes reveals a unique role for
      activating transcription factor 3 in mediating activation of the glycoprotein
      hormone alpha-subunit promoter by gonadotropin-releasing hormone.
AB  - Recent studies profiling immediate early gene responses to GnRH in the LbetaT2
      gonadotrope cell model revealed increased expression of numerous genes including
      activating transcription factor (ATF) 3. The present studies demonstrate similar
      results with GnRH administration in vivo in ovariectomized mice. In this model,
      ATF3 mRNA was markedly up-regulated at 20, 40, and 60 min after in vivo
      administration of a GnRH analog. In alphaT3-1 gonadotrope cells, ATF3 mRNA and
      protein were induced by GnRH in a manner consistent with in vivo observations.
      Pharmacological studies implicated a combined role for the activities of protein
      kinase C isozymes, ERK and c-Jun N-terminal kinase, in modulating ATF3
      expression. The role of ATF3 was further investigated in the activation of the
      human glycoprotein hormone alpha-subunit gene promoter. GnRH induced the alpha
      subunit promoter-luciferase reporter approximately 16-fold, and this induction
      was completely abolished with mutations in the dual cAMP response elements (CREs)
      or the combined inhibition of GnRH-induced ERK and c-Jun N-terminal kinase. GnRH
      induced recruitment of ATF3, c-Jun, and c-Fos to the dual CREs. Overexpression
      and specific knockdown of ATF3 by small inhibitory RNA implicate a functional
      role for ATF3 in mediating activation of the alpha-subunit gene promoter. These
      studies provide clear evidence that ATF3 is a key immediate early gene induced by
      GnRH administration in vivo and in the alphaT3-1 gonadotrope cell model. These
      studies support the conclusion that the dual CREs of the human alpha-subunit
      promoter are the target of GnRH-induced MAPK regulation through ATF3.

PMID- 15961509
TI  - Activin regulates luteinizing hormone beta-subunit gene expression through Smad
      binding and homeobox elements.
AB  - LH beta-subunit (LHbeta), which is essential for ovulation and reproductive
      fitness, is synthesized specifically in pituitary gonadotropes. In this study, we
      show that LHbeta gene expression is induced by activin in mouse primary pituitary
      cells if the cells are treated within 24 h after dispersion in culture.
      Furthermore, male mice deficient in Smad3, and therefore in activin signaling,
      have lower expression of both LHbeta and FSHbeta mRNAs compared with their wild
      type littermates. Using the LbetaT2 immortalized mouse gonadotrope cell line that
      endogenously expresses LH, we identify specific elements in the regulatory region
      of the rat LHbeta gene necessary for its induction by activin. Activin
      responsiveness is conferred by a promoter-proximal region located -121/-86 from
      the transcriptional start site. Maximal LHbeta induction by activin requires a
      homeobox element (HB) and a 5'-early growth response (Egr) site found in this
      region of the promoter. Juxtaposed to the HB are three Smad-binding elements
      (SBEs), which are essential for LHbeta induction. Interestingly, two of the SBEs
      are also critical for basal expression of the LHbeta gene. We demonstrate that
      Smad proteins are necessary and sufficient for activin induction of the LHbeta
      gene. Furthermore, Smad proteins can bind one of the identified SBEs. In addition
      to binding this SBE, Smad proteins interact with pituitary homeobox 1 (Ptx-1) and
      orthodenticle homeobox 1 (Otx-1), which can bind the HB located close to the Smad
      binding site. Thus, activin induction of LHbeta gene expression requires a
      combination of several transcription factors, both basal and activin induced, as
      well as cooperation between multiple DNA elements.

PMID- 15961511
TI  - An underestimated combination of opposites resulting in enhanced thrombotic
      tendency.
AB  - Heterozygous carriers of factor V (FV) Leiden who also carry FV deficiency often
      develop venous thromboembolism, but the thrombosis risk associated with this rare
      condition (pseudohomozygous activated protein C resistance) is still unclear. The
      thrombosis risk of genetically characterized pseudohomozygotes (n = 6) was
      compared with that of FV Leiden heterozygotes (n = 683) and homozygotes (n = 50)
      recruited within a large cohort study on familial thrombophilia. Both thrombin
      generation and Kaplan-Meier thrombosis-free survival analyses were performed in
      different FV genotype groups. FV Leiden pseudohomozygotes showed significantly
      higher thrombosis risk than heterozygotes. The thrombin generation test in
      pseudohomozygotes showed a pattern similar to homozygotes. Accordingly, early
      thrombotic manifestations occurred in pseudohomozygotes at a similar rate as in
      homozygotes. Thus, failure to recognize FV deficiency in FV Leiden heterozygotes
      may result in an underestimate of the thrombosis risk and inadequate management
      of affected patients.

PMID- 15961510
TI  - A FTZ-F1-containing yeast artificial chromosome recapitulates expression of
      steroidogenic factor 1 in vivo.
AB  - Steroidogenic factor 1 (SF-1/Nr5a1) is an orphan nuclear receptor encoded by the
      Ftz-F1 gene and is required for gonad and adrenal development and regulation of
      hormone production within the reproductive and adrenal axes. To extend our
      understanding of Ftz-F1 and its role in SF-1 expression, we identified and
      characterized a yeast artificial chromosome (YAC) containing Ftz-F1. Within this
      YAC, Ftz-F1 is centrally located and flanked by genes encoding a second orphan
      nuclear receptor, germ cell nuclear factor, and proteasome (prosome, macropain)
      subunit beta type 7. Three lines of transgenic mice carrying the YAC were
      generated and in two lines (lines 7 and 14), RT-PCR and ribonuclease protection
      analysis showed that expression of transgenic SF-1 mimicked that of endogenous SF
      1, both spatially and quantitatively. In the third line (line 15), pituitary and
      hypothalamic expression were absent. Comparison of the integrated transgenes
      revealed that line 15 was truncated at the end of intron 4 and revealed a region
      within the locus that is responsible for SF-1 expression in the pituitary and
      hypothalamus. The line 14 transgene was introduced into a mouse strain lacking
      functional SF-1. Examination of SF-1-deficient, transgene-positive mice revealed
      that the YAC was able to rescue adrenal and gonad development, which normally
      arrests in the SF-1-null embryos and showed that the 153-kb transgene integrated
      in line 14 is sufficient to properly direct SF-1 expression and support its
      biological activity. Thus, the study defines a region of Ftz-F1 that contains the
      requisite set of regulatory elements to direct SF-1 cell-specific expression and
      all temporal and quantitative changes need for its biological activity.

PMID- 15961512
TI  - Platelets express functional Toll-like receptor-4.
AB  - Profound thrombocytopenia occurs in humans with sepsis and in mice administered
      lipopolysaccharide (LPS). Growing evidence indicates that platelets may
      contribute to these abnormalities, but whether that is a direct result of LPS
      activation of platelets or an indirect result of other inflammatory mechanisms
      remains unclear. Here we demonstrate that although platelets do not increase P
      selectin expression in response to LPS, platelets bind more avidly to fibrinogen
      under flow conditions in a Toll-like receptor-4 (TLR4)-dependent manner. In
      addition, we find that CD41+ megakaryocytes grown from fetal livers and adult
      circulating platelets express significant amounts of TLR4. LPS induced
      thrombocytopenia in wild-type mice but not in TLR4-deficient (TLR4def) mice. Wild
      type platelets accumulated in the lungs of wild-type mice in response to LPS;
      TLR4def platelets did not. However, wild-type platelets did not accumulate in the
      lungs of LPS-treated TLR4def mice. Neutrophils also accumulated in the lungs, and
      this preceded platelet accumulation. Neutrophil depletion completely abolished
      LPS-induced platelet sequestration into the lungs, but platelet depletion did not
      affect neutrophil accumulation. Thus, our data show for the first time that
      platelets do express functional levels of TLR4, which contribute to
      thrombocytopenia through neutrophil-dependent pulmonary sequestration in response
      to LPS.

PMID- 15961513
TI  - Cooperating cancer-gene identification through oncogenic-retrovirus-induced
      insertional mutagenesis.
AB  - Multiple cooperating mutations that deregulate different signaling pathways are
      required to induce cancer. Identifying these cooperating mutations is a
      prerequisite for developing better combinatorial therapies for treating cancer.
      Here we show that cooperating cancer mutations can be identified through
      oncogenic-retrovirus-induced insertional mutagenesis. Among 13 myeloid leukemias
      induced by transplanting into mice bone marrow cells infected in vitro with a
      replication-defective retrovirus carrying the Sox4 oncogene, 9 contained
      insertional mutations at known or suspected cancer genes. This likely occurred
      because rare bone marrow cells, in which the oncogenic retrovirus happened to
      integrate and in which it mutated a cooperating cancer gene, were selected
      because the host harbored a cooperating cancer mutation. Cooperativity between
      Sox4 and another gene, Mef2c, was subsequently confirmed in transplantation
      studies, in which deregulated Mef2c expression was shown to accelerate the
      myeloid leukemia induced by Sox4. Insertional mutagenesis of cooperating cancer
      genes by a defective oncogenic retrovirus provides a new method for identifying
      cooperating cancer genes and could aid in the development of better therapies for
      treating cancer.

PMID- 15961514
TI  - Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in
      mice.
AB  - Mammalian nonheme iron absorption requires reduction of dietary iron for uptake
      by the divalent metal ion transport system in the intestine. This was thought to
      be mediated by duodenal cytochrome b (Cybrd1), a ferric reductase enzyme resident
      on the luminal surface of intestinal absorptive cells. To test its importance in
      vivo, we inactivated the murine Cybrd1 gene and assessed tissue iron stores in
      Cybrd1-null mice. We found that loss of Cybrd1 had little or no impact on body
      iron stores, even in the setting of iron deficiency. We conclude that other
      mechanisms must be available for the reduction of dietary iron.

PMID- 15961515
TI  - Circulating plasma cells detected by flow cytometry as a predictor of survival in
      302 patients with newly diagnosed multiple myeloma.
AB  - We detected circulating plasma cells (PCs) by flow cytometry in 302 patients with
      newly diagnosed multiple myeloma (MM) by gating on CD38+CD45- cells. The number
      of circulating PCs per 50 000 mononuclear cells was reported. In 80 (27%)
      patients, no circulating PC were seen; 106 (35%) patients had 1 to 10 and 115
      (38%) patients had more than 10 circulating PCs. Median overall survival for the
      302 patients was 47 months. Patients with 10 or fewer circulating PCs had a
      median survival of 58.7 months, whereas patients with more than 10 circulating
      PCs had a median survival of 37.3 months (P = .001). On multivariate analysis,
      the prognostic value of circulating PCs was independent of beta2-microglobulin,
      albumin, and C-reactive protein. There was only a weak correlation between tumor
      mass and circulating PCs, suggesting that the appearance of circulating PCs may
      be a reflection of tumor biology. We conclude that the number of circulating PCs
      measured by flow cytometry in patients with newly diagnosed MM is an independent
      predictor of survival.

PMID- 15961516
TI  - Inhibition of indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus
      infected macrophages in an animal model of HIV-1 encephalitis.
AB  - Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in the kynurenine
      pathway of tryptophan metabolism. IDO activity is linked with immunosuppression
      by its ability to inhibit lymphocyte proliferation, and with neurotoxicity
      through the generation of quinolinic acid and other toxins. IDO is induced in
      macrophages by HIV-1 infection, and it is up regulated in macrophages in human
      brain tissue with HIV-1 encephalitis (HIVE). Using a model of HIVE, we
      investigated whether IDO inhibitor 1-methyl-d-tryptophan (1-MT) could affect the
      generation of cytotoxic T lymphocytes (CTLs) and clearance of virus-infected
      macrophages from the brain. Severe combined immunodeficient mice were
      reconstituted with human peripheral blood lymphocytes, and encephalitis was
      induced by intracranial injection of autologous HIV-1-infected monocyte-derived
      macrophages (MDMs). Animals treated with 1-MT demonstrated increased numbers of
      human CD3+, CD8+, CD8+/interferon-gamma+ T cells, and HIV-1(gag/pol)-specific
      CTLs in peripheral blood compared with controls. At week 2 after MDM injection in
      the basal ganglia, mice treated with 1-MT showed a 2-fold increase in CD8+ T
      lymphocytes in the areas of the brain containing HIV-1-infected MDMs compared
      with untreated controls. By week 3, 1-MT-treated mice showed 89% reduction in HIV
      infected MDMs in brain as compared with controls. Thus, manipulation of
      immunosuppressive IDO activity in HIVE may enhance the generation of HIV-1
      specific CTLs, leading to elimination of HIV-1-infected macrophages in brain.

PMID- 15961517
TI  - SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal
      and engraftment.
AB  - The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial
      action of proteins that determine their self-renewal and/or their commitment to
      differentiation. Stem cell leukemia/T-cell acute lymphoblastic leukemia 1
      (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor, plays key roles
      in controlling the development of primitive and definitive hematopoiesis during
      mouse development but its function in adult HSCs is still a matter of debate. We
      report here that the lentiviral-mediated enforced expression of TAL1 in human
      CD34+ cells marginally affects in vitro the differentiation of committed
      progenitors, whereas in vivo the repopulation capacity of the long-term SCID
      (severe combined immunodeficient) mouse-repopulating cells (LT-SRCs) is enhanced.
      As a consequence, the production of SRC-derived multipotent progenitors as well
      as erythroid- and myeloid-differentiated cells is increased. Looking at the
      lymphoid compartment, constitutive TAL1-enforced expression impairs B- but not T
      cell differentiation. Expression of a mutant TAL1 protein that cannot bind DNA
      specifically impairs human LT-SRC amplification, indicating a DNA-binding
      dependent effect of TAL1 on primitive cell populations. These results indicate
      that TAL1 expression level regulates immature human hematopoietic cell self
      renewal and that this regulation requires TAL1 DNA-binding activity.

PMID- 15961518
TI  - Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune
      responses in vivo and targets interferon-resistant tumor cells.
AB  - Some cutaneous T-cell lymphomas, (CTCLs) clonal T cells are deficient in
      interferon signaling, making them promising targets for viral oncolysis. We
      evaluated cytopathic effects of measles virus (MV) in CTCL. CTCL cell lines and
      infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a
      phase 1 dose escalation trial a total of 16 injections of live MV, Edmonston
      Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL.
      Patients had antimeasles-serum antibodies and were pretreated with interferon
      alpha to prevent uncontrolled virus spread. The well-tolerated treatment with MV
      resulted in clinical responses. Evaluation of biopsies, before and at 11 days
      after injection, by immunohistochemistry and reverse transcriptase-polymerase
      chain reaction (RT-PCR) demonstrated local viral activity with positive staining
      for MV nucleoprotein (NP), an increase of the interferon gamma (IFN-gamma)/CD4
      and IFN-gamma/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients
      demonstrated an increased antimeasles antibody titer after therapy. The data
      demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.

PMID- 15961520
TI  - Alarm pheromone that aggravates stress-induced hyperthermia is soluble in water.
AB  - We previously reported that stressed male Wistar rats released alarm pheromone
      from the perianal region, which aggravated stress-induced hyperthermia and
      increased Fos expression in the mitral/tufted cell layer of the accessory
      olfactory bulb in recipient rats. In this study, we attempted to obtain this
      pheromone in water using these responses as bioassay parameters. Water droplets
      were collected from the ceiling of a box in which no animal was placed, or from a
      box in which an anesthetized donor rat was given electrical stimulation to either
      the neck or perianal regions in order to induce neck odor or alarm pheromone
      release, respectively. Then we placed one of the three kinds of water-containing
      filter papers on the wall of a recipient's home cage and observed heart rate,
      body temperature and behavioral responses, as well as Fos expression in the main
      and accessory olfactory bulbs of the recipient. The water collected from the box
      containing the alarm pheromone was found to generate a reproduction of all of the
      responses seen in the animal that had been directly exposed to alarm pheromone in
      our previous studies. These results suggest that the alarm pheromone is soluble
      in water.

PMID- 15961519
TI  - Differential effects of proteasome inhibition by bortezomib on murine acute graft
      versus-host disease (GVHD): delayed administration of bortezomib results in
      increased GVHD-dependent gastrointestinal toxicity.
AB  - We have recently demonstrated that the proteasome inhibitor, bortezomib,
      administered immediately following murine allogeneic bone marrow transplantation
      (BMT) resulted in marked inhibition of acute graft-versus-host disease (GVHD)
      with retention of graft-versus-tumor effects. We now assessed the effects of
      delayed bortezomib administration (5 or more days after BMT) on GVHD. Recipient
      C57BL/6 (H2b) mice were lethally irradiated and given transplants of bone marrow
      cells and splenocytes from major histocompatibility complex (MHC)-disparate
      BALB/c (H2d) donors. In marked contrast to the effects of bortezomib on GVHD
      prevention when administered immediately after BMT, delayed bortezomib
      administration resulted in significant acceleration of GVHD-dependent morbidity.
      No toxicity was observed following delayed bortezomib administration in models
      where donor T cells were not coadministered, indicating that these deleterious
      effects were critically dependent on GVHD induction. The increase in GVHD
      susceptibility even occurred when late administration of bortezomib was preceded
      by early administration. Pathologic assessment revealed that significant
      increases in gastrointestinal lesions occurred following delayed bortezomib
      administration during GVHD. This pathology correlated with significant increases
      of type 1 tumor necrosis factor alpha (TNF-alpha) receptor transcription in
      gastrointestinal cells and with significant increases of TNF-alpha, interleukin
      1beta (IL-1beta), and IL-6 levels in the serum. These results indicate that the
      differential effects of proteasome inhibition with bortezomib on GVHD are
      critically dependent on the timing of bortezomib administration.

PMID- 15961521
TI  - Olfactory responsiveness to two odorous steroids in three species of nonhuman
      primates.
AB  - Social communication by means of odor signals is widespread among mammals. In
      pigs, for example, the C19-steroids 5-alpha-androst-16-en-3-one and 5-alpha
      androst-16-en-3-ol are secreted by the boar and induce the mating stance in the
      sow. In humans, the same substances have been shown to be compounds of body odor
      and are presumed to affect human behavior. Using an instrumental conditioning
      paradigm, we here show that squirrel monkeys, spider monkeys and pigtail macaques
      are able to detect androstenone at concentrations in the micromolar range and
      thus at concentrations at least as low as those reported in pigs and humans. All
      three species of nonhuman primates were considerably less sensitive to
      androstenol, which was detected at concentrations in the millimolar range.
      Additional tests, using a habituation-dishabituation paradigm, showed that none
      of the 10 animals tested per species was anosmic to the two odorous steroids.
      These results suggest that androstenone and androstenol may be involved in
      olfactory communication in the primate species tested and that the specific
      anosmia to these odorants found in approximately 30% of human subjects may be due
      to their reduced number of functional olfactory receptor genes compared with
      nonhuman primates.

PMID- 15961522
TI  - Development, validation, and evaluation of the PBC-40, a disease specific health
      related quality of life measure for primary biliary cirrhosis.
AB  - BACKGROUND AND AIMS: Study of health related quality of life (HRQOL) and the
      factors responsible for its impairment in primary biliary cirrhosis (PBC) has, to
      date, been limited. There is increasing need for a HRQOL questionnaire which is
      specific to PBC. The aim of this study was to develop, validate, and evaluate a
      patient based PBC specific HRQOL measure. SUBJECTS AND METHODS: A pool of
      potential questions was derived from thematic analysis of indepth interviews
      carried out with 30 PBC patients selected to represent demographically the PBC
      patient population as a whole. This pool was systematically reduced, pretested,
      and cross validated with other HRQOL measures in national surveys involving a
      total of 900 PBC patients, to produce a quality of life profile measure, the PBC
      40, consisting of 40 questions distributed across six domains. The PBC-40 was
      then evaluated in a blinded comparison with other HRQOL measures in a further
      cohort of 40 PBC patients. RESULTS: The six domains of PBC-40 relate to fatigue,
      emotional, social, and cognitive function, general symptoms, and itch. The
      highest mean domain score was seen for fatigue and the lowest for itch. The
      measure has been fully validated for use in PBC and shown to be scientifically
      sound. PBC patient satisfaction, measured in terms of the extent to which a
      questionnaire addresses the problems that they experience, was significantly
      higher for the PBC-40 than for other HRQOL measures. CONCLUSION: The PBC-40 is a
      short easy to complete measure which is acceptable to PBC patients and has
      significantly greater relevance to their problems than other frequently used
      HRQOL measures. Its scientific soundness, shown in extensive testing, makes it a
      valuable instrument for future use in clinical and research settings.

PMID- 15961523
TI  - Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing
      and supporting roles of Shh.
AB  - The inner ear is partitioned along its dorsal/ventral axis into vestibular and
      auditory organs, respectively. Gene expression studies suggest that this
      subdivision occurs within the otic vesicle, the tissue from which all inner ear
      structures are derived. While the specification of ventral otic fates is
      dependent on Shh secreted from the notochord, the nature of the signal
      responsible for dorsal otic development has not been described. In this study, we
      demonstrate that Wnt signaling is active in dorsal regions of the otic vesicle,
      where it functions to regulate the expression of genes (Dlx5/6 and Gbx2)
      necessary for vestibular morphogenesis. We further show that the source of Wnt
      impacting on dorsal otic development emanates from the dorsal hindbrain, and
      identify Wnt1 and Wnt3a as the specific ligands required for this function. The
      restriction of Wnt target genes to the dorsal otocyst is also influenced by Shh.
      Thus, a balance between Wnt and Shh signaling activities is key in distinguishing
      between vestibular and auditory cell types.

PMID- 15961524
TI  - The COP9 signalosome regulates the Neurospora circadian clock by controlling the
      stability of the SCFFWD-1 complex.
AB  - The COP9 signalosome (CSN) promotes the function of SCF-type cullin-based
      ubiquitin ligase complexes in vivo. Paradoxically, removal of the Nedd8
      modification of cullins by CSN inhibits the ubiquitin ligase activity of SCF
      complexes in vitro. Ubiquitination-mediated degradation of the Neurospora
      circadian clock protein FREQUENCY (FRQ) is critical for clock function.
      Ubiquitination of FRQ requires FWD-1, the substrate-recruiting subunit of an SCF
      complex. Here we show that disruption of a subunit of CSN (csn-2) impairs the
      degradation of FRQ and compromises its normal circadian expression. A FRQ
      independent oscillator drives conidiation in the csn-2 mutant, resulting in a 2-d
      conidiation rhythm that persists in constant darkness (DD), constant light (LL),
      light-to-dark (LD) transitions, and temperature cycles. Strikingly, the levels of
      FWD-1 are drastically reduced in csn-2 mutant, explaining the impaired
      degradation of FRQ. Reduction of FWD-1 levels in the mutant requires its F-box,
      suggesting that its degradation is due to autoubiquitination. In addition, SKP-1
      and CUL-1 of the SCF(FWD-1) complex are also unstable in the mutant. Therefore,
      our results establish an important role of CSN in the circadian clock of
      Neurospora. Our findings also reconcile the CSN paradox and suggest that a major
      function of CSN is to maintain the stability of SCF ubiquitin ligases in vivo.

PMID- 15961526
TI  - Preterm birth makes the immature intestine sensitive to feeding-induced
      intestinal atrophy.
AB  - Preterm birth and formula feeding predispose to small intestinal dysfunction,
      which may lead to necrotizing enterocolitis (NEC). In piglets, we tested whether
      the physiological and environmental transitions occurring at birth affect the
      response of the immature intestine to enteral feeding. Pig fetuses (106 days
      gestation, term = 115 days) were prepared with esophageal feeding tubes and fed
      either sow's colostrum (n = 8) or infant formula (n = 7) in utero. After 24 h of
      oral feeding, the pig fetuses were delivered by cesarean section and their
      gastrointestinal morphology and function were compared with those of preterm
      newborn (NB) littermates that were not fed (n = 8) or fed colostrum (n = 7) or
      formula (n = 13) for 24 h after birth. Before birth, both colostrum and formula
      feeding resulted in marked increases in intestinal mass, brush-border enzyme
      activities, and plasma glucagon-like peptide 2 concentrations, to levels similar
      to those in NB colostrum-fed piglets. In contrast, NB formula-fed piglets showed
      reduced intestinal growth, decreased brush-border enzyme activities, and
      intestinal lesions, reflecting NEC. NB formula-fed pigs also showed impaired
      enterocyte endocytotic function and decreased antioxidative capacity, whereas
      brush-border enzyme mRNA levels were unaltered, relative to NB colostrum-fed
      pigs. Our results indicate that the feeding-induced growth and enzyme maturation
      of the immature intestine are not birth dependent. However, with a suboptimal
      diet (milk formula), factors related to preterm birth (e.g., microbial
      colonization and metabolic and endocrine changes) make the immature intestine
      sensitive to atrophy and development of NEC.

PMID- 15961525
TI  - Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells.
AB  - Wnt signaling has been implicated in stem cell (SC) biology, but little is known
      about how stabilized beta-catenin functions within native SC niches. We address
      this by defining the impact of beta-catenin stabilization on maintenance,
      proliferation, and lineage commitment of multipotent follicle SCs when in their
      native niche and in culture. We employ gain of function mutations and inducible
      loss of function mutations to demonstrate that beta-catenin stabilization is
      essential for promoting the transition between SC quiescence and conversion to
      proliferating transit amplifying (TA) progeny. We transcriptionally profile
      purified SCs isolated directly from wild-type and elevated beta-catenin follicles
      in both resting and activated states to uncover the discrete set of genes whose
      expression in native SCs is dependent upon beta-catenin stabilization. Finally,
      we address the underlying mechanism and show that in the SC niche, Wnt signaling
      and beta-catenin stabilization transiently activate Lef1/Tcf complexes and
      promote their binding to target genes that promote TA cell conversion and
      proliferation to form the activated cells of the newly developing hair follicle.
      We also show that these changes precede subsequent Wnt signals that impact on the
      TA progeny to specify the differentiation lineages of the follicle.

PMID- 15961527
TI  - Angiotensin-converting enzyme inhibition attenuates myonuclear addition in
      overloaded slow-twitch skeletal muscle.
AB  - Because optimal overload-induced skeletal muscle hypertrophy requires ANG II, we
      aimed to determine the effects of blocking ANG II production [via angiotensin
      converting enzyme (ACE) inhibition] on potential mediators of hypertrophy in
      overloaded skeletal muscle, namely, myonuclear addition and fibroblast content.
      In a 2 x 2 design, adult (200-225 g) female Sprague-Dawley rats were placed into
      one of four groups (n = 8/group): 7-day skeletal muscle overload, sham operation,
      7-day skeletal muscle overload with ACE inhibition, or sham operation with ACE
      inhibition. Functional overloads of the plantaris and soleus muscles were
      produced via bilateral surgical ablation of the synergistic gastrocnemius muscle,
      and ACE inhibition was accomplished by the addition of the ACE inhibitor
      enalapril maleate to the animals' daily drinking water (0.3 mg/ml). Myonuclear
      addition and extrasarcolemmal nuclear proliferation, as measured by in vivo 5
      bromo-2'-deoxyuridine labeling, were significantly (P < or = 0.05) increased by
      overload in both the slow-twitch soleus and fast-twitch plantaris muscles.
      Furthermore, ACE inhibition attenuated these overload-induced increases in the
      soleus muscle but not in the plantaris muscle. However, the effect of ACE
      inhibition on soleus extrasarcolemmal nuclei was not likely due to differences in
      fibroblast content because overload elicited significant increases in vimentin
      positive areas in soleus and plantaris muscles, and these areas were unaffected
      by ACE inhibition in either muscle. There was no effect of ACE inhibition on any
      measure in sham-operated muscles. Collectively, these data indicate that ANG II
      may mediate the satellite cell response to overload in slow-twitch soleus but not
      in fast-twitch plantaris muscles and that this effect may occur independently of
      changes in fibroblast content.

PMID- 15961528
TI  - Increased corpus cavernosum smooth muscle tone associated with partial bladder
      outlet obstruction is mediated via Rho-kinase.
AB  - Numerous studies have now demonstrated that lower urinary tract symptoms (LUTS)
      are associated with erectile dysfunction (ED) in men independent of age or
      general health. Because one-third of men over the age of 50 will develop LUTS and
      a recent study showed ED in 62% of patients presenting for LUTS, the importance
      of determining the mechanistic link between these two pathologies is clear. Using
      a rabbit model of partial bladder outlet obstruction (PBOO), a primary cause of
      LUTS, we have identified an increased basal corpus cavernosum smooth muscle
      (CCSM) tone associated with an elevated level of smooth muscle myosin (SMM)
      phosphorylation in PBOO compared with sham-operated control rabbits (sham).
      Results from in vitro kinase and phosphatase assays using purified smooth muscle
      myosin showed increased kinase and decreased phosphatase activities in cellular
      extracts from corpora cavernosa isolated from PBOO compared with sham rabbits.
      Increased Rho-kinase expression in the CCSM of PBOO rabbits was suggested by the
      observations that Rho-kinase inhibitors attenuated the increased kinase activity
      and were less effective in relaxing CCSM strips from PBOO vs. sham rabbits. This
      hypothesis was then confirmed by RT-PCR and Western blotting, which demonstrated
      increased expression of both isoforms of Rho-kinase (ROKalpha and ROKbeta).
      Increased SMM basal phosphorylation (necessary for SM contraction) in the CCSM of
      PBOO rabbits, mediated via an increase in Rho-kinase expression/activity, would
      be expected to make the CCSM more difficult to relax (necessary for erection),
      which suggests that the RhoA/Rho-kinase pathway as being involved in the
      mechanism for LUTS-associated ED.

PMID- 15961529
TI  - Newborn lamb coronary artery reactivity is programmed by early gestation
      dexamethasone before the onset of systemic hypertension.
AB  - Exposure of the early gestation ovine fetus to exogenous glucocorticoids induces
      organ-specific alterations in postnatal cardiovascular physiology. To determine
      whether early gestation corticosteroid exposure alters coronary reactivity before
      the development of systemic hypertension, dexamethasone (0.28 mg x kg(-1) x day(
      1)) was administered to pregnant ewes by intravenous infusion over 48 h beginning
      at 27 days gestation (term, 145 days). Vascular responsiveness was assessed in
      endothelium-intact coronary arteries isolated from 1-wk-old steroid-exposed and
      age-matched control lambs (N = 6). Calcium imaging was performed in fura 2-loaded
      primary cultures of vascular smooth muscle cells (VSMC) from the harvested
      coronary arteries. Early gestation steroid exposure did not significantly alter
      mean arterial blood pressure or coronary reactivity to KCl, thromboxane A(2)
      mimetic U-46619, or ANG II. Steroid exposure significantly increased coronary
      artery vasoconstriction to acetylcholine and endothelin-1. Vasodilatation to
      adenosine, but not nitroprusside or forskolin, was significantly attenuated
      following early gestation steroid exposure. Endothelin-1 or U-46619 stimulation
      resulted in a comparable increase in intracellular calcium concentration
      ([Ca(2+)](i)) in coronary VSMC isolated from either dexamethasone-treated or
      control animals. However, the ANG II- or KCl-mediated increase in [Ca(2+)](i) in
      control VSMC was significantly attenuated in VSMC harvested from dexamethasone
      treated lambs. Coronary expression of muscle voltage-gated l-type calcium channel
      alpha-1 subunit protein was not significantly altered by steroid exposure,
      whereas endothelial nitric oxide synthase expression was attenuated. These
      findings demonstrate that early gestation glucocorticoid exposure elicits primary
      alterations in coronary responsiveness before the development of systemic
      hypertension. Glucocorticoid-induced alterations in coronary physiology may
      provide a mechanistic link between an adverse intrauterine environment and later
      cardiovascular disease.

PMID- 15961532
TI  - Renal cortical and medullary blood flow responses to L-NAME and ANG II in wild
      type, nNOS null mutant, and eNOS null mutant mice.
AB  - Experiments in wild-type (WT; C57BL/6J) mice, endothelial nitric oxide synthase
      null mutant [eNOS(-/-)] mice, and neuronal NOS null mutant [nNOS(-/-)] mice were
      performed to determine which NOS isoform regulates renal cortical and medullary
      blood flow under basal conditions and during the infusion of ANG II. Inhibition
      of NOS with N(omega)-nitro-l-arginine methyl ester (l-NAME; 50 mg/kg iv) in
      Inactin-anesthetized WT and nNOS(-/-) mice increased arterial blood pressure by
      28-31 mmHg and significantly decreased blood flow in the renal cortex (18-24%)
      and the renal medulla (13-18%). In contrast, blood pressure and renal cortical
      and medullary blood flow were unaltered after l-NAME administration to eNOS(-/-)
      mice, indicating that NO derived from eNOS regulates baseline vascular resistance
      in mice. In subsequent experiments, intravenous ANG II (20 ng x kg(-1) x min(-1))
      significantly decreased renal cortical blood flow (by 15-25%) in WT, eNOS(-/-),
      nNOS(-/-), and WT mice treated with l-NAME. The infusion of ANG II, however, led
      to a significant increase in medullary blood flow (12-15%) in WT and eNOS(-/-)
      mice. The increase in medullary blood flow following ANG II infusion was not
      observed in nNOS(-/-) mice, in WT or eNOS(-/-) mice pretreated with l-NAME, or in
      WT mice administered the nNOS inhibitor 5-(1-imino-3-butenyl)-l-ornithine (1 mg x
      kg(-1) x h(-1)). These data demonstrate that NO from eNOS regulates baseline
      blood flow in the mouse renal cortex and medulla, while NO produced by nNOS
      mediates an increase in medullary blood flow in response to ANG II.

PMID- 15961531
TI  - Dose-related effects of lauric acid on antropyloroduodenal motility,
      gastrointestinal hormone release, appetite, and energy intake in healthy men.
AB  - We recently reported that intraduodenal infusion of lauric acid (C12) (0.375
      kcal/min, 106 mM) stimulates isolated pyloric pressure waves (IPPWs), inhibits
      antral and duodenal pressure waves (PWs), stimulates release of cholecystokinin
      (CCK) and glucagon-like peptide-1 (GLP-1), and suppresses energy intake and that
      these effects are much greater than those seen in response to isocaloric decanoic
      acid (C10) infusion. Administration of C12 was, however, associated with nausea,
      confounding interpretation of the results. The aim of this study was to evaluate
      the effects of different intraduodenal doses of C12 on antropyloroduodenal (APD)
      motility, plasma CCK and GLP-1 concentrations, appetite, and energy intake.
      Thirteen healthy males were studied on 4 days in double-blind, randomized
      fashion. APD pressures, plasma CCK and GLP-1 concentrations, and appetite
      perceptions were measured during 90-min ID infusion of C12 at 0.1 (14 mM), 0.2
      (28 mM), or 0.4 (56 mM) kcal/min or saline (control; rate 4 ml/min). Energy
      intake was determined at a buffet meal immediately following infusion. C12 dose
      dependently stimulated IPPWs, decreased antral and duodenal motility, and
      stimulated secretion of CCK and GLP-1 (r > 0.4, P < 0.05 for all). C12 (0.4
      kcal/min) suppressed energy intake compared with control, C12 (0.1 kcal/min), and
      C12 (0.2 kcal/min) (P < 0.05). These effects were observed in the absence of
      nausea. In conclusion, intraduodenal C12 dose-dependently modulated APD motility
      and gastrointestinal hormone release in healthy male subjects, whereas effects on
      energy intake were only apparent with the highest dose infused (0.4 kcal/min),
      possibly because only at this dose was modulation of APD motility and
      gastrointestinal hormone secretion sufficient for a suppressant effect on energy
      intake.

PMID- 15961530
TI  - Chronic estradiol and progesterone treatment in conscious dogs: effects on
      insulin sensitivity and response to hypoglycemia.
AB  - We evaluated the effect of chronic (3 wk) subcutaneous treatment with
      progesterone and estradiol (PE; producing serum levels observed in the 3rd
      trimester of pregnancy) or placebo (C) on hepatic and whole body insulin
      sensitivity and response to hypoglycemia in conscious, overnight-fasted
      nonpregnant female dogs, using tracer and arteriovenous difference techniques.
      Insulin was infused peripherally for 3 h at 1.8 mU x kg(-1) x min(-1). Glucose
      was allowed to fall to 3 mM (Hypo) or maintained at 6 mM (Eugly) by peripheral
      glucose infusion. Insulin concentrations were significantly higher in Eugly-PE (n
      = 7) and Hypo-PE (n = 7) than in Eugly-C (n = 6) and Hypo-C groups (n = 7), but
      there were no significant differences in hepatic insulin extraction.
      Concentrations of glucagon, cortisol, epinephrine, and norepinephrine did not
      differ significantly between Eugly groups or between Hypo groups. Whole body
      glucose disposal, adjusted for the differences in insulin between groups, was 35%
      higher in Eugly-C vs. Eugly-PE groups (P < 0.05). Eugly-C and Eugly-PE groups
      exhibited similar rates of net hepatic glucose uptake, but the rate of glucose
      appearance was greater in Eugly-PE in the last hour (P < 0.05). Net hepatic
      glucose output was greater (P < 0.05) in Hypo-PE than in Hypo-C groups, and the
      glucose infusion rate required to maintain equivalent hypoglycemia was less (P <
      0.05). The rate of gluconeogenic flux did not differ between Hypo groups. Chronic
      progesterone and estradiol exposure caused whole body (primarily skeletal muscle)
      insulin resistance and enhanced the liver's response to hypoglycemia without
      altering counterregulatory hormone concentrations.

PMID- 15961533
TI  - Hypoxic pulmonary vasoconstriction in reptiles: a comparative study of four
      species with different lung structures and pulmonary blood pressures.
AB  - Low O2 levels in the lungs of birds and mammals cause constriction of the
      pulmonary vasculature that elevates resistance to pulmonary blood flow and
      increases pulmonary blood pressure. This hypoxic pulmonary vasoconstriction (HPV)
      diverts pulmonary blood flow from poorly ventilated and hypoxic areas of the lung
      to more well-ventilated parts and is considered important for the local matching
      of ventilation to blood perfusion. In the present study, the effects of acute
      hypoxia on pulmonary and systemic blood flows and pressures were measured in four
      species of anesthetized reptiles with diverse lung structures and heart
      morphologies: varanid lizards (Varanus exanthematicus), caimans (Caiman
      latirostris), rattlesnakes (Crotalus durissus), and tegu lizards (Tupinambis
      merianae). As previously shown in turtles, hypoxia causes a reversible
      constriction of the pulmonary vasculature in varanids and caimans, decreasing
      pulmonary vascular conductance by 37 and 31%, respectively. These three species
      possess complex multicameral lungs, and it is likely that HPV would aid to secure
      ventilation-perfusion homogeneity. There was no HPV in rattlesnakes, which have
      structurally simple lungs where local ventilation-perfusion inhomogeneities are
      less likely to occur. However, tegu lizards, which also have simple unicameral
      lungs, did exhibit HPV, decreasing pulmonary vascular conductance by 32%, albeit
      at a lower threshold than varanids and caimans (6.2 kPa oxygen in inspired air
      vs. 8.2 and 13.9 kPa, respectively). Although these observations suggest that HPV
      is more pronounced in species with complex lungs and functionally divided hearts,
      it is also clear that other components are involved.

PMID- 15961534
TI  - P-glycoprotein and breast cancer resistance protein expression in human placentae
      of various gestational ages.
AB  - Placental efflux transporters such as P-glycoprotein (P-gp) and breast cancer
      resistance protein (BCRP) protect the developing fetus from exposure to
      potentially toxic xenobiotics. However, little is known about the expression of
      these transporters in human placentae of different gestational ages. Therefore,
      we quantified the expression of P-gp and BCRP in human placentae of different
      gestational ages. We also measured the expression of various nuclear regulatory
      factors such as the pregnane xenobiotic factor to determine whether their
      expression also changes with gestational age. Syncitial microvillous plasma
      membranes were isolated from human placentae of various gestational ages (60-90
      days, 90-120 days, and full-term C-section placentae). P-gp and BCRP expression
      (protein) in these preparations were measured by Western blot analysis followed
      by an ELISA. Expression (mRNA) of P-gp, BCRP, and nuclear regulatory factors in
      the placentae were quantified by quantitative real-time PCR. P-gp expression
      (relative to that of alkaline phosphatase) was significantly (P < 0.05) higher
      (44.8-fold as protein; 6.5-fold as mRNA) in early gestational age human placentae
      (60-90 days) vs. term placentae. In contrast, BCRP (protein and mRNA) and nuclear
      regulatory factors (mRNA) expression in placental tissue did not change
      significantly with gestational age. However, placental expression of P-gp and
      human chorionic gonadotropin-beta (hCG-beta) transcripts was highly correlated (r
      = 0.73; P < 0.0001; Spearman rank correlation). Expression of P-gp, but not BCRP,
      decreases dramatically with gestational age in human placentae. This decrease in
      P-gp expression is not caused by a change in expression of nuclear receptor
      transcripts but appears to be related to hCG-beta expression. The placental P-gp
      expression appears to be upregulated in early pregnancy to protect the fetus from
      xenobiotic toxicity at a time when it is most vulnerable to such toxicity.

PMID- 15961535
TI  - Daily expression of clock genes in whole blood cells in healthy subjects and a
      patient with circadian rhythm sleep disorder.
AB  - In recent years, circadian rhythm sleep disorders in humans have been increasing.
      Clinical features characteristic of this disorder are well known, but the
      specific causes remain unknown. However, various derangements of circadian
      expression of the clock gene are a probable cause of this disease. We have
      attempted to elucidate the relationship between the expression of the clock genes
      in whole blood cells and the clinical features characteristic of this disorder.
      In this study, we indicate the daily expression of clock genes period (Per) 1, 2,
      3, Bmal1, and Clock in whole blood cells in 12 healthy male subjects. The peak
      phase of Per1, Per2, and Per3 appeared in the early morning, whereas that of
      Bmal1 and Clock appeared in the midnight hours. Furthermore, in one patient case
      with circadian rhythm sleep disorder, we observed variations of the peak phase in
      clock genes by treatments such as light therapy, exercise therapy, and medicinal
      therapy. This study suggested that the monitoring of human clock genes in whole
      blood cells, which may be functionally important for the molecular control of the
      circadian pacemaker as well as in suprachiasmatic nucleus, might be useful to
      evaluate internal synchronization.

PMID- 15961536
TI  - Programming of glucose-insulin metabolism in adult sheep after maternal
      undernutrition.
AB  - The present study examines the effects of late vs. early gestation undernutrition
      on adult glucose-insulin homeostasis in sheep and investigates whether the lower
      birth weight of twins alters glucose-insulin handling in adult life. Pregnant
      sheep were fed to requirement (100% intake) from day 0 of gestation to term [
      approximately 147 days of gestation (dGA), control singles (CS) n = 5; control
      twins (CT) n = 5] or to 50% requirement from days 0-30 dGA [nutrient restricted
      during early gestation (NRE); n = 5] or day 110-term [NR during late nutrition
      (NRL); n = 4]. At all other times, NR sheep received 100% intake. All sheep
      lambed naturally; offspring were weaned at 10 wk and were reared on pasture until
      1 yr of age. At this time, indwelling catheters were inserted, and 2-4 days
      later, basal metabolic and endocrine status and responses to an intravenous
      glucose tolerance test (IVGTT) and feeding were assessed. Adipose and skeletal
      muscle were then sampled after humane euthanasia and were analyzed for expression
      of insulin-signaling proteins and GLUT4. Between groups, birth weight of
      singletons was similar and increased relative to twins. At 1 yr of age, weights
      were similar between groups. The areas under the curve for glucose and insulin
      during the IVGTT were greater in NRL vs. other groups, indicating glucose
      intolerance. This was associated with reduced adipose, but not muscle, GLUT4, and
      increased adipose tissue mass. Adult glucose-insulin homeostasis in sheep was
      unaffected by fetal number. In conclusion, prenatal undernutrition, specifically
      during late gestation, affects adult offspring intermediary metabolism, and, in
      particular, glucose-insulin homeostasis.

PMID- 15961537
TI  - Effects of 7-day amino acid infusion on renal growth, function, and renin
      angiotensin system in fetal sheep.
AB  - These experiments examined whether renal growth and the fetal renin-angiotensin
      system could be stimulated by infusion of amino acids and whether chronic amino
      acid infusions restored glomerulotubular balance, which had been disrupted during
      4-h infusions. Five fetal sheep aged 122 +/- 1 days gestation received an
      infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22
      mmol/min for 7 days. Six control fetuses were given saline at the same rate (5
      ml/h). Kidney wet weights after amino acid infusion were 28% larger than control
      fetuses (P < 0.05), and renal angiotensinogen mRNA levels were approximately 2.6
      fold higher (P < 0.005). Circulating renin levels and renal renin mRNA levels
      were suppressed (P < 0.05), and renal renin protein levels tended to be lower.
      Arterial pressure was increased, and there was a marked, sustained natriuresis
      and diuresis. Glomerular filtration rate and filtered sodium were approximately
      two-fold higher throughout infusion (P < 0.05). Fractional proximal sodium
      reabsorption, suppressed at 4 h (from 73.4 +/- 6.5 to 53.7 +/- 10.2%), did not
      return to control levels (36.1 +/- 3.4% on day 7, P < 0.05). Distal sodium
      reabsorption was markedly increased (from 79 +/- 25 to 261 +/- 75 mumol/min by
      day 7, P < 0.005), but this was not sufficient to restore glomerulotubular
      balance. The resultant high rates of sodium excretion led to hyponatremia and
      polyhydramnios. In conclusion, long-term amino acid infusions increased renal
      angiotensinogen gene expression, kidney weight, and distal nephron sodium
      reabsorptive capacity but failed to restore proximal and total glomerulotubular
      balance.

PMID- 15961538
TI  - Modest maternal protein restriction fails to program adult hypertension in female
      rats.
AB  - Modest maternal dietary protein restriction in the rat leads to hypertension in
      adult male offspring. The purpose of this study was to determine whether female
      rats are resistant to developing the increased blood pressure seen in male rats
      after maternal protein restriction. Pregnant rats were fed a normal protein (19%,
      NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and
      ANG II levels were reduced by 50-65% in male LP compared with NP pups, but were
      not suppressed in female LP compared with female NP. Mean arterial pressure in
      conscious, chronically instrumented adult female offspring (22 wk) was not
      different in LP (LP: 120 +/- 3 mmHg vs. NP: 121 +/- 2 mmHg), and glomerular
      filtration rate was also not different in LP vs. NP. The number of glomeruli per
      kidney was similar in adult LP and NP female offspring (LP: 26,050 +/- 2,071 vs.
      NP: 26,248 +/- 1,292, NP), and individual glomerular volume was also not
      different (LP: 0.92 +/- 0.11 10(6) microm(3), LP vs. NP: 1.07 +/- 0.11 10(6)
      microm(3)); the total volume of all glomeruli per kidney was also not
      significantly different. Thus female rats are relatively resistant to the
      programming for adult hypertension by perinatal protein restriction that we have
      described in males. This resistance may be due to the fact that modest maternal
      protein restriction does not reduce the number of glomeruli with which females
      are endowed as it does in males. The intrarenal renin-angiotensin system during
      development may play a key role in this protective effect of female gender.

PMID- 15961539
TI  - Interactive drives from two brain stem premotor nuclei are essential to support
      rat tail sympathetic activity.
AB  - Anatomical studies indicate that sympathetic preganglionic neurons receive inputs
      from several brain stem cell groups, but the functional significance of this
      organization for vasomotor control is not known. We studied the roles of two
      brain stem premotor cell groups, the medullary raphe and the rostral
      ventrolateral medulla (RVLM), in determining the activity of sympathetic
      vasomotor supply to the tail of urethane-anesthetized, artificially ventilated
      rats. Chemical inactivation of either RVLM (bilaterally) or raphe cells by
      microinjecting glycine (120-200 nl, 0.5 M) or muscimol (40-160 nl, 2.1-8 mM) was
      sufficient to inhibit ongoing tail sympathetic fiber activity and to block its
      normally strong response to mild cooling via the trunk skin (reducing rectal
      temperature from 38.5 to 37 degrees C). After bilateral RVLM inactivation, tail
      sympathetic fibers could still be excited by chemical stimulation of raphe
      neurons (l-glutamate, 120 nl, 50 mM), and strong cooling (rectal temperature
      approximately 33 degrees C) caused a low level of ongoing activity. After
      chemical inhibition of raphe neurons, however, neither strong cooling nor
      chemical stimulation of RVLM neurons activated tail sympathetic fibers.
      Electrical stimulation of the RVLM elicited tail sympathetic fiber volleys before
      and after local anesthesia of the raphe (150-500 nl of 5% tetracaine),
      demonstrating the existence of an independent descending excitatory pathway from
      the RVLM. The data show that neurons in both the medullary raphe and the RVLM,
      acting together, provide the essential drive to support vasomotor tone to the
      tail. Inputs from these two premotor nuclei interact in a mutually facilitatory
      manner to determine tonic, and cold-induced, tail sympathetic activity.

PMID- 15961540
TI  - Phenotypic and functional characterization of adult brain neuropoiesis.
AB  - The modern concept of neurogenesis in the adult brain is predicated on the
      premise that multipotent glial cells give rise to new neurons throughout life.
      Although extensive evidence exists indicating that this is the case, the
      transition from glial to neuronal phenotype remains poorly understood. A unique
      monolayer cell-culture system was developed to induce, expose, and recapitulate
      the entire developmental series of events of subventricular zone (SVZ)
      neurogenesis. We show here, using immunophenotypic, ultrastructural,
      electrophysiological, and time-lapse analyses, that SVZ-derived glial fibrillary
      acidic protein(low)/A2B5+/nestin+ candidate founder cells undergo metamorphosis
      to eventually generate large numbers of fully differentiated interneuron
      phenotypes. A model of postnatal neurogenesis is considered in light of known
      embryonic events and reveals a limited developmental potential of SVZ
      stem/progenitor cells, whereby ancestral cells in both embryonic and
      postnatal/adult settings give rise to glia and GABAergic interneurons.

PMID- 15961541
TI  - Accelerated chemically induced tumor development mediated by CD4+CD25+ regulatory
      T cells in wild-type hosts.
AB  - We examined the role of CD4+CD25+ regulatory T cells in the development of 3
      methylcholanthrene (MCA)-induced tumors. Immunization of wild-type BALB/c mice
      with a series of SEREX (serological identification of antigens by recombinant
      expression cloning)-defined broadly expressed self-antigens results in the
      development of highly active CD4+CD25+ regulatory T cells. Accelerated tumor
      development was observed in mice immunized with self-antigens and was abolished
      by antibody-mediated depletion of CD4+ T cells or CD25+ T cells. A similar
      acceleration of tumorigenesis was also observed in mice adoptively transferred 2
      or 4 weeks after MCA injection with CD4+CD25+ T cells derived from mice immunized
      with DnaJ-like 2, one of these self-antigens. Experiments with Jalpha281-/- mice
      lacking invariant natural killer (iNK) T cells indicated that iNK T cells, known
      for their protective role in the development of MCA-induced tumors, were
      suppressed in immunized hosts. NK cells, also known to play a protective role in
      MCA induced-tumorigenesis, were also suppressed in mice immunized with
      serologically defined self-antigens in a CD4+CD25+ T cell-dependent manner. We
      propose that CD4+CD25+ regulatory T cells generated by immunization with these
      self-antigens enhance susceptibility to MCA induced-tumorigenesis by down
      regulating iNK T and NK reactivity, and suggest that these observations provide
      direct evidence for the existence of cancer immunosurveillance in this system of
      chemical carcinogenesis.

PMID- 15961542
TI  - Long-term cortical plasticity evoked by electric stimulation and acetylcholine
      applied to the auditory cortex.
AB  - Auditory fear conditioning with tone bursts followed by electric leg stimulation
      activates neurons not only in the auditory and somatosensory systems but also in
      many other regions of the brain and elicits shifts in the best frequencies (BFs)
      of collicular and cortical neurons, i.e., reorganization of the frequency (co
      chleotopic) maps in the inferior colliculus and auditory cortex (AC). What are
      the neural elements minimally necessary for evoking long-term cortical BF shifts?
      We found that: (i) both electric stimulation and acetylcholine applied to the AC
      evoke the long-term cortical BF shift as does the conditioning; (ii) both
      electric stimulation of the AC and acetylcholine applied to the inferior
      colliculus increase the short-term collicular BF shift evoked by the cortical
      electric stimulation but do not change it into long-term; and (iii) as this short
      term collicular BF shift is blocked by atropine, the development of the long-term
      cortical BF shift becomes slow and small. Therefore, the most essential neural
      elements for evoking the long-term cortical BF shift are the AC, corticofugal
      feedback and the cholinergic nucleus. Our current data support the Gao-Suga
      model, which hypothesizes that the small short-term cortical BF shifts are evoked
      by tonal stimuli without the association of conditioned and unconditioned stimuli
      in the multisensory thalamic nuclei and that these BF shifts are augmented and
      changed into the large long-term BF shifts by cholinergic neurons.

PMID- 15961543
TI  - Reelin promoter hypermethylation in schizophrenia.
AB  - Reelin mRNA and protein levels are reduced by approximately 50% in various
      cortical structures of postmortem brain from patients diagnosed with
      schizophrenia or bipolar illness with psychosis. In addition, the mRNA encoding
      the methylating enzyme, DNA methyltransferase 1, is up-regulated in the same
      neurons that coexpress reelin and glutamic acid decarboxylase 67. We have
      analyzed the extent and pattern of methylation within the CpG island of the
      reelin promoter in genomic DNA isolated from cortices of schizophrenia patients
      and nonpsychiatric subjects. Ten (The Stanley Foundation Neuropathology
      Consortium) and five (Harvard Brain Collection) schizophrenia patients and an
      equal number of nonpsychiatric subjects were selected from each brain collection.
      Genomic DNA was isolated, amplified (from base pair -527 to base pair +322) after
      bisulphite treatment, and sequenced. The results show that within the promoter
      region there were interesting regional variations. There was increased
      methylation at positions -134 and 139, which is particularly important for
      regulation, because this portion of the promoter is functionally competent based
      on transient transfection assays. This promoter region binds a protein present in
      neuronal precursor nuclear extracts that express very low levels of reelin mRNA;
      i.e., an oligonucleotide corresponding to this region and that contains
      methylated cytosines binds more tightly to extracts from nonexpressing cells than
      the nonmethylated counterpart. Collectively, the data show that this promoter
      region has positive and negative properties and that the function of this complex
      cis element relates to its methylation status.

PMID- 15961544
TI  - Single-file electrophoretic transport and counting of individual DNA molecules in
      surfactant nanotubes.
AB  - We demonstrate a complete nanotube electrophoresis system (nanotube radii in the
      range of 50 to 150 nm) based on lipid membranes, comprising DNA injection, single
      molecule transport, and single-molecule detection. Using gel-capped electrodes,
      electrophoretic single-file transport of fluorescently labeled dsDNA molecules is
      observed inside nanotubes. The strong confinement to a channel of molecular
      dimensions ensures a detection efficiency close to unity and identification of
      DNA size from its linear relation to the integrated peak intensity. In addition
      to constituting a nanotechnological device for identification and quantification
      of single macromolecules or biopolymers, this system provides a method to study
      their conformational dynamics, reaction kinetics, and transport in cell-like
      environments.

PMID- 15961546
TI  - Simple cystatin C-based prediction equations for glomerular filtration rate
      compared with the modification of diet in renal disease prediction equation for
      adults and the Schwartz and the Counahan-Barratt prediction equations for
      children.
AB  - BACKGROUND: Serum creatinine is the most commonly used marker for estimation of
      glomerular filtration rate (GFR). To compensate for its drawbacks as a GFR
      marker, several prediction equations including several parameters are being used,
      with the Modification of Diet in Renal Disease (MDRD), Schwartz, and Counahan
      Barratt equations being the ones most widely accepted for estimation of relative
      GFR in mL x min(-1) x (1.73 m(2))(-1). The present study analyzes whether these
      GFR prediction equations for adults and children might be replaced by simple
      prediction equations based on plasma concentrations of cystatin C. METHODS: Data
      from 536 patients (0.3-93 years), consecutively referred for determination of GFR
      by an invasive gold standard procedure, were used for the analysis. Calculations
      of bias (median percentage of error), correlation (adjusted R(2)), and percentage
      of estimates within 30% and 50% of measured GFR were used in the comparisons.
      RESULTS: A cystatin C-based prediction equation using only concentration in mg/L
      and a prepubertal factor: GFR [mL x min(-1) x (1.73 m(2))(-1)] = 84.69 x cystatin
      C (mg/L)(-1.680) x 1.384 (if a child <14 years) assessed GFR equally well or
      better than the simplified MDRD, the Schwartz, and the Counahan-Barratt
      prediction equations for the adult (> or =18 years) and juvenile groups of the
      investigated cohort. Age did not influence the cystatin C-based prediction
      equation for adults, whereas gender did, but with a factor close to unity (0.948
      for females). CONCLUSION: A GFR prediction equation based solely on cystatin C
      (in mg/L) and a prepubertal factor might replace the simplified MDRD prediction
      equation for adults and the Schwartz and Counahan-Barratt prediction equations
      for children.

PMID- 15961545
TI  - Fibronectin controls cap-dependent translation through beta1 integrin and
      eukaryotic initiation factors 4 and 2 coordinated pathways.
AB  - Fibronectin (FN) is a major matrix protein involved in multiple processes. Little
      is known about how adhesion to FN affects the translational machinery. We show
      that in fibroblasts adhesion to FN triggers translation through the coordinated
      regulation of eukaryotic initiation factors (eIFs) 4F and 2 and is impaired by
      blocking beta1 integrin engagement. FN-stimulated translation has unique
      properties: (i) it is highly sensitive to the inhibition of phosphatidylinositol
      3-kinase (PI3K), but not to the inhibition of mammalian target of rapamycin,
      downstream of PI3K; (ii) there is no synergy between serum-stimulated translation
      and FN-dependent translation; (iii) FN-dependent translation, unlike growth
      factor-stimulated translation, does not lead to increased translocation of 5'
      terminal oligopyrimidine tract mRNAs to polysomes; and (iv) cells devoid of
      attachment to matrix show an impairment of initiation of translation accompanied
      by phosphorylation of eIF2alpha, which cannot be reverted by active PI3K. These
      findings indicate that integrins may recruit the translational machinery in a
      unique way and that FN-dependent translation cannot be blocked by mammalian
      target of rapamycin inhibition.

PMID- 15961547
TI  - Maternal serum invasive trophoblast antigen and first-trimester Down syndrome
      screening.
AB  - BACKGROUND: In the United States, Down syndrome screening is still performed
      mainly in the second trimester, using 3 or 4 markers. Moving screening into the
      first trimester has the advantage of earlier diagnosis. Currently, first
      trimester screening typically includes maternal serum pregnancy-associated plasma
      protein-A (PAPP-A), the free beta-subunit of human chorionic gonadotropin (free
      beta), and ultrasound measurement of nuchal translucency thickness (NT). The
      current report describes a case-control study of serum invasive trophoblast
      antigen (ITA) and its possible inclusion in first-trimester screening for Down
      syndrome. METHODS: As part of an earlier observational study, serum samples from
      54 Down syndrome and 276 matched unaffected pregnancies were collected between 9
      and 15 weeks of gestation. Samples had been aliquoted and stored at -20 degrees C
      for 8 years. ITA was measured and converted to weight-adjusted multiples of the
      median (MoM). The distributions of other first-trimester markers are from a
      single published study. RESULTS: Median ITA MoM in Down syndrome pregnancies
      increase as gestational age increases (2.02 MoM at 11 and 2.44 MoM at 13
      completed weeks). At 75% detection, maternal age in combination with ITA and PAPP
      A measurements have an 8.0% false-positive rate, slightly lower than the 8.8%
      found for the free beta and PAPP-A combination; adding NT measurements reduces
      false positives for the 2 combinations to 2.0% and 1.8%, respectively.
      CONCLUSION: Serum ITA appears to be a useful first-trimester Down syndrome marker
      that could replace free beta measurements while maintaining performance.

PMID- 15961548
TI  - Human kallikrein 4: quantitative study in tissues and evidence for its secretion
      into biological fluids.
AB  - BACKGROUND: Human kallikrein 4 (hK4) is a proteolytic enzyme belonging to the
      tissue kallikrein family of serine proteases. Previous tissue expression studies
      have demonstrated highest KLK4 mRNA expression in prostatic tissue, but there has
      been only limited evidence for the presence of hK4 protein in prostate and other
      tissues and in corresponding biological secretions. METHODS: To investigate the
      concentrations of hK4 in tissues and biological fluids, we developed a new hK4
      specific sandwich-type immunoassay using a monoclonal antibody as the capture
      reagent. RESULTS: The assay has a detection limit of 0.02 microg/L and <0.1%
      cross-reactivity toward any of the other 14 human kallikreins. Twelve of 40
      tissue extracts prepared from various human tissues contained detectable hK4
      concentrations (0.68-7143 ng/g of total protein), with healthy prostate tissue
      containing the highest amount of hK4. Examination of 16 malignant and 18 benign
      prostate tissues revealed no significant differences in hK4 protein content, and
      the tissues contained a wide range of values (benign, <0.02 to 801 ng/g;
      malignant, <0.02 to 824 ng/g). Among the biological fluids tested, seminal plasma
      and urine contained widely varying amounts of hK4; concentrations in 54 urine
      samples were <0.02 to 2.6 microg/L, whereas concentrations in 58 seminal plasma
      samples were 0.2-202 microg/L. Affinity purification of hK4 from seminal plasma
      and subsequent mass spectrometry demonstrated the secreted nature of hK4 in
      seminal plasma. CONCLUSIONS: hK4 is found primarily in prostate tissue and is
      secreted in seminal plasma. Its value as a novel prostatic biomarker needs to be
      defined further.

PMID- 15961549
TI  - Case-control and two-gate designs in diagnostic accuracy studies.
AB  - BACKGROUND: In some diagnostic accuracy studies, the test results of a series of
      patients with an established diagnosis are compared with those of a control
      group. Such case-control designs are intuitively appealing, but they have also
      been criticized for leading to inflated estimates of accuracy. METHODS: We
      discuss similarities and differences between diagnostic and etiologic case
      control studies, as well as the mechanisms that can lead to variation in
      estimates of diagnostic accuracy in studies with separate sampling schemes
      ("gates") for diseased (cases) and nondiseased individuals (controls). RESULTS:
      Diagnostic accuracy studies are cross-sectional and descriptive in nature.
      Etiologic case-control studies aim to quantify the effect of potential causal
      exposures on disease occurrence, which inherently involves a time window between
      exposure and disease occurrence. Researchers and readers should be aware of
      spectrum effects in diagnostic case-control studies as a result of the restricted
      sampling of cases and/or controls, which can lead to changes in estimates of
      diagnostic accuracy. These spectrum effects may be advantageous in the early
      investigation of a new diagnostic test, but for an overall evaluation of the
      clinical performance of a test, case-control studies should closely mimic cross
      sectional diagnostic studies. CONCLUSIONS: As the accuracy of a test is likely to
      vary across subgroups of patients, researchers and clinicians might carefully
      consider the potential for spectrum effects in all designs and analyses,
      particularly in diagnostic accuracy studies with differential sampling schemes
      for diseased (cases) and nondiseased individuals (controls).

PMID- 15961550
TI  - New reference intervals for thyrotropin and thyroid hormones based on National
      Academy of Clinical Biochemistry criteria and regular ultrasonography of the
      thyroid.
AB  - BACKGROUND: The aim of our present study was to establish new reference intervals
      for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical
      Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also
      assessed the effect of potentially confounding factors to modulate the limits of
      these intervals. METHODS: We investigated 870 apparently healthy persons and
      excluded, step by step, those with a family history of thyroid disease,
      pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase
      or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the
      entire group were finally included as reference collective. We measured serum
      concentrations of TSH, total and free thyroxine (T(4) and FT(4)), and total and
      free triiodothyronine (T(3) and FT(3)) of the whole and the reference collective
      on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and
      97.5th percentiles for comparison. RESULTS: The calculated lower limit for TSH
      differed significantly between the reference intervals for healthy persons with
      an assessed normal thyroid gland vs the nonselected group of healthy blood
      donors. Age was the only independent factor and was significantly inversely
      associated with TSH (P <0.0001). Use of oral contraceptives was a significant
      predictor for variation in T(4) concentrations (P <0.001). Age and oral
      contraceptives were independently associated with T(3) variations (P <0.05). For
      FT(4) vs FT(3) variation, gender and (inversely) age (P <0.01) were independent
      modulating factors. CONCLUSIONS: The selection of healthy persons according to
      NACB criteria combined with sonographic confirmation of a normal thyroid gland
      provide a valid basis for the reference interval for TSH. Factors indicating a
      preclinical disease state, such as family history, pathologic ultrasonography
      result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies,
      can be associated with normal hormone concentrations. Additionally, patient age
      and gender as well as use of contraceptives should be considered in diagnostic
      evaluation of thyroid diseases.

PMID- 15961551
TI  - Quantification of lipoprotein subclasses by proton nuclear magnetic resonance
      based partial least-squares regression models.
AB  - BACKGROUND: Cardiovascular disease risk can be estimated in part on the basis of
      the plasma lipoprotein profile. Analysis of lipoprotein subclasses improves the
      risk evaluation, but the traditional methods are very time-consuming. Novel,
      rapid, and productive methods are therefore needed. METHODS: We obtained plasma
      samples from 103 fasting people and determined the plasma lipoprotein subclass
      profiles by an established ultracentrifugation-based method. Proton nuclear
      magnetic resonance (NMR) spectra were obtained from replicate samples on a 600
      MHz NMR spectrometer. From the ultracentrifugation-based reference data and the
      NMR spectra, we developed partial least-squares (PLS) regression models to
      predict cholesterol and triglyceride (TG) concentrations in plasma as well as in
      VLDL, intermediate-density lipoprotein (IDL), LDL, 3 LDL fractions, HDL, and 3
      HDL subclasses. RESULTS: The correlation coefficients (r) between the plasma TG
      and cholesterol concentrations measured by the 2 methods were 0.98 and 0.91,
      respectively. For LDL- and HDL-cholesterol concentrations, r = 0.90 and 0.94,
      respectively. For cholesterol concentrations in the LDL-1, LDL-2, and LDL-3
      fractions, r = 0.74, 0.78, and 0.69, respectively, and for HDL subclasses
      HDL(2b), HDL(2a), and HDL(3), cholesterol concentrations were predicted with r =
      0.92, 0.94, and 0.75, respectively. TG concentrations in VLDL, IDL, LDL, and HDL
      were predicted with correlations of 0.98, 0.85, 0.77, and 0.74, respectively. The
      cholesterol and TG concentrations in the main lipoprotein fractions and in LDL
      fractions and HDL subclasses predicted by the PLS models were 94%-100% of the
      concentrations obtained by ultracentrifugation. CONCLUSION: NMR-based PLS
      regression models are appropriate for use in research in which analyses of the
      plasma lipoprotein profile, including LDL and HDL subclasses, are required in
      large numbers of samples.

PMID- 15961552
TI  - Biological variation of total prostate-specific antigen: a survey of published
      estimates and consequences for clinical practice.
AB  - BACKGROUND: The objectives of this study were to determine whether a single
      result for total prostate-specific antigen (tPSA) can be used confidently to
      guide the need for prostate biopsy and by how much serial tPSA measurements must
      differ to be significant. tPSA measurements include both analytical and
      biological components of variation. The European Group on Tumor Markers conducted
      a literature survey to determine both the magnitude and impact of biological
      variation on single, the mean of replicate, and serial tPSA measurements.
      METHODS: The survey yielded 27 studies addressing the topic, and estimates for
      the biological variation of tPSA could be derived from 12 of these studies.
      RESULTS: The mean biological variation was 20% in the concentration range 0.1-20
      microg/L for men over 50 years. The biological variation means that the one-sided
      95% confidence interval (CI) of the dispersion for a single tPSA result is
      approximately 33%. Three replicate samples with one analysis on each narrow the
      one-sided 95% CI for the mean concentration to approximately 20% and facilitate
      decisions on prostate biopsy. During monitoring of serial measurements, the
      change needed for significance is approximately 50% (P <0.05). CONCLUSIONS: The
      biological variation of tPSA has implications for screening, diagnosis, and
      monitoring. Single measurements may not be sufficiently precise for screening and
      diagnosis. Replicate samples and calculation of the mean concentration may
      improve precision by reducing the dispersion. Monitoring of tPSA requires an
      estimate of either the change needed for significance or, alternatively, of the
      significance of the change.

PMID- 15961553
TI  - Testosterone measurement by isotope-dilution liquid chromatography-tandem mass
      spectrometry: validation of a method for routine clinical practice.
AB  - BACKGROUND: Immunoassay is unsatisfactory for measuring the testosterone
      concentrations typically found in women. Bench-top tandem mass spectrometers are
      a viable alternative technology for measurements in the clinical laboratory.
      METHODS: We used stable-isotope dilution liquid chromatography-tandem mass
      spectrometry (ID/LC-MS/MS) to measure testosterone in plasma and serum. The
      sample volume was 50 muL in duplicate; preparation and analysis were carried out
      in a single tube, and a batch of 192 tubes was analyzed in 17.5 h. RESULTS: Intra
      and interassay imprecision was <15% in the range 0.3-49 nmol/L. Recovery of
      testosterone added to samples at concentrations of 0.625-20 nmol/L was 96% (CV =
      12%; n = 26). Six samples were serially diluted with double charcoal-stripped
      serum to demonstrate linearity. Correlation (r(2)) with isotope-dilution gas
      chromatography-mass spectrometry for 20 pools of clinical samples (range, 0.5
      38.5 nmol/L) was 0.99. Correlations with our extraction RIA were 0.97 for
      clinical samples from men (range, 8-46.3 nmol/L) and 0.66 for samples from women
      (range, 0.7-3.0 nmol/L), but were 0.35 for male samples containing <3 nmol/L
      testosterone and 0.77 for female samples containing >8 nmol/L. Various steroids
      added to double charcoal-stripped serum showed no interference at the retention
      time of the testosterone peak. CONCLUSIONS: The ID/LC-MS/MS method has improved
      accuracy compared with immunoassay. The low sample volume and simplicity,
      rapidity, and robustness of the method make it suitable for use as a high
      throughput assay in routine clinical biochemistry laboratories.

PMID- 15961554
TI  - Melanocortinergic modulation of cholecystokinin-induced suppression of feeding
      through extracellular signal-regulated kinase signaling in rat solitary nucleus.
AB  - Signals from the gut and hypothalamus converge in the caudal brainstem to control
      ingestive behavior. We have previously shown that phosphorylation of ERK1/2 in
      the solitary nucleus (NTS) is necessary for food intake suppression by exogenous
      cholecystokinin (CCK). Here we test whether this intracellular signaling cascade
      is also involved in the integration of melanocortin-receptor (MCR) mediated
      inputs to the caudal brainstem. Using fourth ventricular-cannulated rats and
      Western blotting of NTS tissue, we show that the MC4R agonist melanotan II (MTII)
      rapidly and dose-dependently increases phosphorylation of both ERK1/2 and cAMP
      response element-binding protein (CREB). Sequential administration of fourth
      ventricular MTII and peripheral CCK at doses that alone produced submaximal
      stimulation of pERK1/2 produced an additive increase. Prior fourth ventricular
      administration of the MC4R antagonist SHU9119 completely abolished the CCK
      induced increases in pERK and pCREB and, in freely feeding rats, SHU9119
      significantly increased meal size and satiety ratio. Prior administration of the
      MAPK kinase inhibitor U0126 abolished the capacity of MTII to suppress 2-h food
      intake and significantly decreased MTII-induced ERK phosphorylation in the NTS.
      Furthermore, pretreatment with the cAMP inhibitor, cAMP receptor protein-Rp
      isomer, significantly attenuated stimulation of pERK induced by either CCK or
      MTII. The results demonstrate that activation of the ERK pathway is necessary for
      peripheral CCK and central MTII to suppress food intake. The cAMP-->ERK-->CREB
      cascade may thus constitute a molecular integrator for converging satiety signals
      from the gut and adiposity signals from the hypothalamus in the control of meal
      size and food intake.

PMID- 15961555
TI  - Orexin expression and function: glucocorticoid manipulation, stress, and feeding
      studies.
AB  - We investigated the effects of glucocorticoid manipulation on orexin-A-induced
      feeding and prepro-orexin mRNA levels in the lateral hypothalamic area (LHA) of
      the rat brain. Adrenalectomy (ADX) reduced orexin-A-induced feeding over 4 h by
      about 60%, compared with shams, an effect that was reversed by corticosterone
      (CORT) replacement. ADX had no effect on prepro-orexin mRNA levels in the LHA in
      either the morning or the evening; however, message was up-regulated by CORT in
      the morning but not the evening. An increased number of emulsion grains per cell
      in the LHA suggests that this is a specific increase in prepro-orexin mRNA and is
      not due to an increased number of cells expressing message. Prepro-orexin mRNA
      levels in the LHA were elevated 4 h after injection of lipopolysaccharide,
      compared with saline-injected controls. Partial but not complete abolition of
      orexin-A-induced feeding by ADX suggests that orexin-A-induced feeding may be
      mediated through glucocorticoid-dependent and glucocorticoid-independent
      pathways. In the morning increased prepro-orexin mRNA after CORT replacement
      demonstrates that orexin expression is sensitive to increased concentrations of
      glucocorticoids. However, the lack of effect of ADX on prepro-orexin mRNA levels
      suggests that endogenous glucocorticoids are not involved in tonic regulation of
      basal prepro-orexin expression. Overall our data constitute a body of evidence
      for an integrated relationship between central orexin expression, stress,
      glucocorticoid manipulation, and feeding patterns in the rat.

PMID- 15961556
TI  - Fibroblast growth factor-23 mutants causing familial tumoral calcinosis are
      differentially processed.
AB  - Familial tumoral calcinosis (TC, OMIM 211900) is a heritable disorder
      characterized by hyperphosphatemia, normal or elevated serum 1,25
      dihydroxyvitamin D, and often severe ectopic calcifications. Two recessive
      mutations in fibroblast growth factor-23 (FGF23), serine 71/glycine (S71G) and
      serine 129/phenylalanine (S129F), were identified as causing TC. Herein, we
      undertook comprehensive biochemical analyses of an extended TC family carrying
      the S71G FGF23 mutation, which revealed that heterozygous (serine/glycine, S/G)
      individuals had elevated serum FGF23 C-terminal fragments compared with wild-type
      (serine/serine, S/S) family members (P < 0.025). To understand the differential
      processing of FGF23 in TC patients, we transiently expressed S71G as well as
      S129F FGF23. FGF23 ELISA in tandem with Western analyses revealed increased
      proteolytic cleavage of mutant FGF23 and a limited secretion of intact protein.
      Furthermore, S71G and S129F FGF23 carrying mutations that disrupt the furin-like
      protease RXXR motif in FGF23 rescued the secretion of the intact protein, and
      both TC mutant proteins harboring the R176Q mutation revealed no altered
      sensitivity to trypsin compared with the native (R176Q)FGF23. Finally, S71G, but
      not S129F mutant FGF23, is rescued by temperature. In summary, FGF23 mutations
      causing TC lead to increased intracellular proteolysis of FGF23, most likely by
      furin-like proteases, due to conformational changes of the mutant protein. The
      destabilizing nature of these mutations provides new insight into the
      pathophysiology of TC and exemplifies the physiological importance of FGF23 in
      phosphate and vitamin D metabolism.

PMID- 15961558
TI  - XXY mice exhibit gonadal and behavioral phenotypes similar to Klinefelter
      syndrome.
AB  - Klinefelter syndrome (XXY males) is the most common sex chromosome aneuploidy.
      XXY mice were generated by using a four-generation breeding scheme that involves
      the use of a structurally rearranged Y chromosome, Y*, yielding approximately 50%
      of the live-born male offspring in the fourth generation with a XXY karyotype.
      Adult XXY mice have small testes, decreased plasma T levels, and elevated plasma
      FSH levels. The testes of adult XXY mice contained small seminiferous tubules
      with intraepithelial vacuolization and absence of germ cells, whereas Leydig
      cells appeared to be more abundant than their XY littermates. Androgen receptor
      immunoexpression was localized in Leydig cells and peritubular myoid cells in
      both XY and XXY mice. Androgen receptor immunoexpression was abundant in the
      Sertoli cells of XY mice but nearly absent in those of XXY mice. The testicular
      phenotype was marked by a 23.1% decrease in testis weights in XXY pups beginning
      at d 7 after birth. Gonocyte numbers were similar in XY and XXY mice at d 1 of
      age, followed by a 62.6% decrease in the number of gonocytes in the XXY mice on d
      3 and further progressive loss in spermatogonia by d 5 and 7. On d 10, only a few
      spermatogonia remained in the XXY mice. To determine whether the phenotype of XXY
      mice extended into the neurobehavioral domain, studies were conducted
      demonstrating impairment of learning and memory function in XXY mice. We conclude
      that adult XXY mice have testicular failure and learning deficits, similar to its
      human counterpart, Klinefelter syndrome.

PMID- 15961557
TI  - Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)
      beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary
      lactotropes.
AB  - The neurotransmitter dopamine is known to inhibit prolactin secretion and the
      proliferation of lactotropes in the pituitary gland. In this study, we determined
      whether dopamine and TGFbeta1 interact to regulate lactotropic cell
      proliferation. We found that dopamine and the dopamine agonist bromocriptine
      stimulated TGFbeta1 secretion and TGFbeta1 mRNA expression but inhibited
      lactotropic cell proliferation both in vivo and in vitro. The dopamine's
      inhibitory action on lactotropic cell proliferation was blocked by a TGFbeta1
      neutralizing antibody. We also found that PR1 cells, which express low amounts of
      the dopamine D2 receptor, demonstrated reduced expression of TGFbeta1 type II
      receptor and TGFbeta1 mRNA levels and had undetectable levels of TGFbeta1
      protein. These cells showed a reduced TGFbeta1 growth-inhibitory response.
      Constitutive expression of the D2 receptor short isoform, but not the D2 receptor
      long isoform, induced TGFbeta1 and TGFbeta1 type II receptor gene expression and
      recovered dopamine- and TGFbeta1-induced growth inhibition in PR1 cells. The
      constitutive expression of D2 receptor short isoform also reduced the tumor cell
      growth rate. These data suggest that a TGFbeta1 system may mediate, in part, the
      growth-inhibitory action of dopamine on lactotropes.

PMID- 15961559
TI  - Maternal nutritional programming of fetal adipose tissue development:
      differential effects on messenger ribonucleic acid abundance for uncoupling
      proteins and peroxisome proliferator-activated and prolactin receptors.
AB  - Maternal nutrient restriction at specific stages of gestation has differential
      effects on fetal development such that the offspring are programmed to be at
      increased risk of a range of adult diseases, including obesity. We investigated
      the effect of maternal nutritional manipulation through gestation on fetal
      adipose tissue deposition in conjunction with mRNA abundance for uncoupling
      protein (UCP)1 and 2, peroxisome proliferator-activated receptors (PPAR)alpha and
      gamma, together with long and short forms of the prolactin receptor (PRLR).
      Singleton-bearing ewes were either nutrient restricted (3.2-3.8 MJ day(-1)
      metabolizable energy) or fed to appetite (8.7-9.9 MJ day(-1)) over the period of
      maximal placental growth, i.e. between 28 and 80 d gestation. After 80 d
      gestation, ewes were either fed to calculated requirements, (6.7-7.5 MJ day(-1)),
      or to appetite (8.0-10.9 MJ day(-1)). At term, offspring of nutrient-restricted
      ewes possessed more adipose tissue, an adaptation that was greatest in those born
      to mothers that fed to requirements in late gestation. This was accompanied by an
      increased mRNA abundance for UCP2 and PPARalpha, an adaptation not seen in
      mothers re-fed to appetite. Maternal nutrition had no effect on mRNA abundance
      for UCP1, PPARgamma, or PRLR. Irrespective of maternal nutrition, mRNA abundance
      for UCP1 was positively correlated with PPARgamma and the long and short forms of
      PRLR, indicating that these factors may act together to ensure that UCP1
      abundance is maximized in the newborn. In conclusion, we have shown, for the
      first time, differential effects of maternal nutrition on key regulatory
      components of fetal fat metabolism.

PMID- 15961560
TI  - Transforming growth factor-beta3 increases gap-junctional communication among
      folliculostellate cells to release basic fibroblast growth factor.
AB  - Folliculostellate (FS) cells are known to communicate with each other and with
      endocrine cells via gap junctions in the anterior pituitary. We investigated
      whether TGFbeta3 and estradiol, known to regulate FS cell production and
      secretion of basic fibroblast growth factor (bFGF), increases gap junctional
      communication to alter bFGF secretion from FS cells. FS cells in monolayer
      cultures were treated with TGFbeta3 or vehicle alone for 24 h and then
      microinjected with Lucifer Yellow and high-molecular-weight Texas Red dextran.
      Ten minutes later the transfer of dye among adjacent cells was recorded with a
      digital microscope. TGFbeta3 increased the transfer of dye. The TGFbeta3
      neutralizing antibody and the gap junction inhibitor octanol reduced the effect
      of TGFbeta3 on the transfer of dye. The TGFbeta3-induced transfer of dye was
      unaltered by simultaneous treatment with estradiol. The steroid alone also had no
      effect. TGFbeta3 increased total and phosphorylated levels of connexin 43.
      Estradiol treatment did not produce any significant changes on basal or TGFbeta3
      induced increases in connexin 43 levels. The gap-junction inhibitor octanol
      reduced TGFbeta3-increased levels of bFGF in FS cells. Taken together, these
      results suggest that TGFbeta3 may act on FS cells to increase gap-junctional
      communication to maximize its effect on bFGF secretion.

PMID- 15961561
TI  - Functional effects of transforming growth factor beta on adhesive properties of
      porcine trophectoderm.
AB  - In pigs, expression and amounts of biologically active TGFbetas at the conceptus
      maternal interface increase significantly as conceptuses elongate and begin the
      implantation process. Before their activation, secreted TGFbetas are
      noncovalently associated with their respective, isoform-specific latency
      associated peptides (LAPs), which contain the Arg-Gly-Asp (RGD) amino acid
      sequence that serves as a ligand for numerous integrins. Objectives of this study
      were to determine whether TGFbeta1 increases production of fibronectin by porcine
      trophectoderm, whether porcine trophectoderm adheres specifically to fibronectin
      and LAP, and whether functional interactions between porcine trophectoderm and
      the two TGFbeta-associated proteins, fibronectin and LAP, are integrin mediated.
      Porcine trophectoderm cells (pTr2) were cultured in presence of TGFbeta1, LAP, or
      pan-neutralizing anti-TGFbeta antibody; TGFbeta specifically increased (P < 0.05)
      fibronectin mRNA levels, as determined by Northern and slot blot analyses.
      Immunofluorescence microscopy demonstrated a TGFbeta-induced increase in
      fibronectin in pTr2 cells. In dispersed cell adhesion assays, adhesion of pTr2
      cells to fibronectin was inhibited by an RGD-containing peptide (P < 0.05) and
      pTr2 cells attached to recombinant LAP but not to an LAP mutant, which contained
      an RGE sequence rather than the RGD site (P < 0.05). Fibronectin- and LAP-coated
      microbeads induced integrin activation at apical surfaces of both trophectoderm
      and uterine luminal epithelial cells, as indicated by aggregation and
      transmembrane accumulation of talin detected with immunofluorescence microscopy.
      Cell surface biotinylation and immunoprecipitation revealed integrin subunits
      alphav and beta1 on apical membranes of pTr2 cells. These results suggest
      multiple effects of TGFbeta at the porcine conceptus-maternal interface,
      including integrin-mediated conceptus-maternal communication through LAP.

PMID- 15961562
TI  - Expression, regulation, and function of paired-box gene 8 in the human placenta
      and placental cancer cell lines.
AB  - Pax proteins are transcriptional regulators that control a variety of
      developmental decisions in vertebrates. During development, the paired-box gene 8
      (PAX8) is expressed in the thyroid, kidney, and several areas of the central
      nervous system. It is also expressed in the adult thyroid gland, in which it
      mediates TSH-induced modulation of the expression of important genes, such as
      those encoding thyroglobulin, thyroperoxidase, and the sodium/iodide symporter
      (NIS). Thus far, placental expression of PAX8 has been described only in mice. In
      the present study, we show that PAX8 is also expressed in the human placenta at
      term. In an in vitro model of placental cancer, the JAR choriocarcinoma cell
      line, human chorionic gonadotropin (hCG) increased levels of PAX8 mRNA and
      protein, and gel retardation assays indicated that the up-regulation of PAX8
      protein expression is associated with an increase in its DNA-binding activity.
      The effects of hCG were mimicked by forskolin, indicating that they are cAMP
      dependent. Levels of mRNA for the Wilms' tumor 1 (WT1) and NIS genes were
      increased in JAR cells by hCG treatment, whereas overexpression of PAX8 increased
      only levels of WT1 mRNA. In cells transfected with PAX8-specific small
      interfering RNA, the stimulatory effects of hCG on WT1 mRNA levels were
      abolished, but hormonal enhancement of NIS mRNA levels was unchanged. These
      findings indicate that, in JAR cells, hCG activates a cAMP-dependent pathway that
      can up-regulate WT1 expression through PAX8.

PMID- 15961563
TI  - Bazedoxifene acetate: a selective estrogen receptor modulator with improved
      selectivity.
AB  - We assessed the preclinical characteristics of a novel, stringently screened
      selective estrogen receptor modulator, bazedoxifene acetate, including its
      ability to bind to and activate estrogen receptors and promote increased bone
      mineral density and bone strength in rats, and the effects impacting the uterine
      endometrium, breast cancer cell proliferation, and central nervous system
      associated vasomotor responses in an animal model. Bazedoxifene bound to estrogen
      receptor-alpha with an IC50 of 26 nm, an affinity similar to that of raloxifene.
      Bazedoxifene did not stimulate proliferation of MCF-7 cells but did inhibit
      17beta-estradiol-induced proliferation with an IC50 of 0.19 nm. In an immature
      rat uterine model, bazedoxifene (0.5 and 5.0 mg/kg) was associated with less
      increase in uterine wet weight than either ethinyl estradiol (10 microg/kg) or
      raloxifene (0.5 and 5.0 mg/kg). Histological analysis revealed that
      coadministration of bazedoxifene also appeared to reduce raloxifene-stimulated
      endometrial luminal epithelial cell and myometrial cell hypertrophy. In
      ovariectomized rats, bazedoxifene was associated with significant increases in
      bone mineral density at 6 wk, compared with control, and better compressive
      strength of bone samples from the L4 vertebrae, compared with samples from
      ovariectomized animals. In the morphine-addicted rat model of vasomotor activity,
      bone-sparing doses of bazedoxifene alone were not associated with 17beta
      estradiol inhibition of increased vasomotor activity. Bazedoxifene acetate
      represents a promising new treatment for osteoporosis, with a potential for less
      uterine and vasomotor effects than selective estrogen receptor modulators
      currently used in clinical practice. Controlled clinical trial data will be
      needed to confirm these effects.

PMID- 15961564
TI  - Differential increase in forebrain and caudal neurosecretory system corticotropin
      releasing factor and urotensin I gene expression associated with seawater
      transfer in rainbow trout.
AB  - Transfer to seawater (SW) in rainbow trout elicits an increase in plasma cortisol
      and a bout of anorexia. Although the corticotropin-releasing factor (CRF) system
      has known hypophysiotropic and anorexigenic properties, it is not known whether
      CRF-related peptides originating from either the forebrain or the caudal
      neurosecretory system (CNSS) play a role during SW acclimation. Therefore, we
      examined the effects of SW transfer on food intake, plasma osmolality,
      hypothalamic-pituitary-interrenal axis activity, and the expression of CRF and
      urotensin I (UI) in the forebrain and the CNSS. While SW transfer chronically
      suppressed food intake over a 2-wk period, it transiently increased plasma
      osmolality, ACTH, and cortisol. Similarly, 24 h after SW transfer, hypothalamic
      and preoptic area CRF mRNA levels were significantly increased but recovered to
      pretransfer levels within 7 d. Conversely, SW transfer elicited a delayed
      increase in hypothalamic UI mRNA levels and had no effect on preoptic area UI
      expression. In the CNSS, SW exposure was associated with parallel increases in
      CRF and UI mRNA levels from 24 h post transfer through 7 d. Finally, in situ
      hybridization demonstrated an extensive and overlapping pattern of CNSS CRF and
      UI expression. These results differentially implicate specific neuronal
      populations of the CRF system in the acute and chronic responses to a
      hyperosmotic stress and suggest that forebrain and CNSS CRF-related peptides have
      different roles in the coordinated response to fluid balance disturbances.

PMID- 15961565
TI  - Cultured embryonic hippocampal neurons deficient in glucocorticoid (GC) receptor:
      a novel model for studying nongenomic effects of GC in the neural system.
AB  - Glucocorticoid (GC) acts through both genomic and nongenomic mechanisms. It
      affects the structure and function of the central nervous system, especially the
      hippocampus. Here we report an in vitro culture system that can yield embryonic
      hippocampal neurons deficient in the expression of GC receptor as demonstrated by
      immunoblotting, immunocytochemistry, and RT-PCR. Owing to this unique feature,
      those neuron preparations can serve as an ideal model for studying the nongenomic
      actions of GC on neural cells. In this study, we found that the Erk1/2, c-Jun N
      terminal kinase (JNK), and p38 MAPKs were activated in these neurons by BSA
      conjugated corticosterone within 15 min of treatment. This activation was not
      blocked by RU38486, spironolactone, or cycloheximide. Therefore, it is concluded
      that the activation of MAPKs observed here was due to the nongenomic action of
      GC. Furthermore, a 24-h incubation with corticosterone at concentrations ranged
      from 10(-11)-10(-5) M did not have an effect on the viability of GC receptor
      deficient neurons.

PMID- 15961566
TI  - Tunicate gonadotropin-releasing hormone (GnRH) peptides selectively activate
      Ciona intestinalis GnRH receptors and the green monkey type II GnRH receptor.
AB  - In vertebrates, GnRH binds to its receptor and stimulates predominantly G(q/11)
      mediated signal transduction in gonadotropes. However, little is known about the
      GnRH receptor and its signaling pathway in tunicates, a group that arose before
      the vertebrates. Although tunicates have had duplications of a few genes in the
      last 600 million years, the early vertebrates had duplications of the full
      genome. Also unknown is the nature of GnRH signaling in the tunicate, which lacks
      both a pituitary gland and sex steroids. However, we know that tunicates have
      GnRH peptides because we previously reported six GnRH peptides encoded within the
      tunicate genome of Ciona intestinalis. Here we clone and sequence cDNAs for four
      putative GnRH receptors from C. intestinalis. These are the only invertebrate
      GnRH receptors found to date. Each Ciona GnRH receptor was expressed in COS-7
      cells, incubated with each of the six C. intestinalis GnRHs and assayed for a
      signaling response. GnRH receptors 1, 2, and 3 responded to Ciona GnRH peptides
      to stimulate intracellular cAMP accumulation. In contrast, only GnRH receptor 1
      activated inositol phosphate turnover in response to one of the Ciona GnRHs. The
      green monkey type II GnRH receptor cDNA was tested as a comparison and a positive
      control. In conclusion, the four GnRH receptors encoded within the C.
      intestinalis genome were all transcribed into messenger RNA, but only three of
      the Ciona GnRH receptors were biologically active in our assays. The Ciona GnRH
      receptors almost exclusively activated the cAMP pathway.

PMID- 15961567
TI  - The effects of early headgear treatment on dental arches and craniofacial
      morphology: an 8 year report of a randomized study.
AB  - The aim of this study was to determine the long-term effects of early headgear
      (HG) treatment on craniofacial structures. The total study group comprised 68
      children (40 males and 28 females) aged 7.6 years (standard deviation 0.3 years).
      The children, who had a Class II tendency in occlusion and moderate crowding,
      were randomly divided into two groups of equal size. In the first group, HG
      treatment was initiated immediately. In the second group, which served as a
      control group, only minor interceptive procedures were performed during the first
      follow-up period of 2 years. During the 8 year follow-up, orthodontic therapy,
      including fixed appliances and possible extractions, was carried out when
      necessary. The results showed that the most evident difference between the groups
      was the wider and longer dental arches in the HG group, which could only partly
      be explained by the higher rate of extractions in the control group. For the
      cephalometric measurements, the most significant difference was in the maxillary
      plane orientation. The peer assessment rating (PAR) score, showing the general
      outcome of treatment, was at the same level in both groups at follow-up. The
      deficit of the early HG treatment was the longer mean total treatment time,
      resulting from the two-phase treatment.

PMID- 15961568
TI  - Perceptions of facial aesthetics in two and three dimensions.
AB  - The aims of this study were to investigate whether the preferred facial
      relationship chosen by professionals and the general public is Class I and to
      ascertain whether viewing two-dimensional (2D) or three-dimensional (3D) images
      had any effect on the ranking of facial attractiveness. Orthodontists (n = 47),
      maxillofacial surgeons (n = 25) and members of the general public (n = 78)
      assessed 2D and 3D facial scans of two males and two females that had been
      morphed to produce five images reflecting different skeletal patterns: Class I,
      mild and moderate Class II, and mild and moderate Class III. Each assessor placed
      the images in rank order of preference, after viewing alternate 2D and 3D image
      formats for each face. The data were analysed using logistic regression. In 2D,
      professionals (orthodontists and maxillofacial surgeons) chose Class I as the
      preferred facial image more frequently than the general public for only one of
      the four faces. However, in 3D format they chose Class I as the preferred facial
      image for some subject faces more, and others less, frequently when compared with
      the general public. The gender of the assessor was not significant when assessing
      the preferred facial relationship for Class I images in either 2D or 3D formats.
      The oldest assessors (56+ years) were significantly less likely than the younger
      age groups to select Class I as the preferred facial relationship in both 2D and
      3D. In summary, there was too great a degree of variation to say that a
      difference between 2D and 3D facial images was evident.

PMID- 15961569
TI  - The influence of lower face vertical proportion on facial attractiveness.
AB  - This study investigated the influence of changing lower face vertical proportion
      on the attractiveness ratings scored by lay people.Ninety-two social science
      students rated the attractiveness of a series of silhouettes with normal, reduced
      or increased lower face proportions. The random sequences of 10 images included
      an image with the Eastman normal lower face height relative to total face height
      [lower anterior face height/total anterior face height (LAFH/TAFH) of 55 per
      cent], and images with LAFH/TAFH increased or decreased by up to four standard
      deviations (SD) from the Eastman norm. All the images had a skeletal Class I
      antero-posterior (AP) relationship. A duplicate image in each sequence assessed
      repeatability. The participants scored each image using a 10 point numerical
      scale and also indicated whether they would seek treatment if the image was their
      own profile. The profile image with normal vertical facial proportions was rated
      by the lay people as the most attractive. Attractiveness scores reduced as the
      vertical facial proportions diverged from the normal value. Images with a reduced
      lower face proportion were rated as significantly more attractive than the
      corresponding images with an increased lower face proportion. Images with a
      reduced lower face proportion were also significantly less likely to be judged as
      needing treatment than the corresponding images with an increased lower face
      proportion.

PMID- 15961570
TI  - Space conditions and dental and occlusal features in patients with palatally
      impacted maxillary canines: an aetiological study.
AB  - The aetiology of palatal canine impaction is unclear. The aim of this research
      was to investigate the occlusal features that could contribute to the aetiology
      of palatal maxillary canine impaction. The material consisted of the pre
      treatment dental casts of 34 patients (27 female and seven male) with unilateral
      palatal canine impaction (impaction group). The average age of this group was
      17.7 years (+/- 4.6). These were matched according to age, gender and type of
      malocclusion with a comparison group of pre-treatment dental casts from
      unaffected orthodontic patients. From the dental casts the following parameters
      were obtained: (1) dentoalveolar arch relationship, (2) missing or anomalous
      teeth, (3) the mesiodistal width of each maxillary tooth, (4) the upper arch
      perimeter, (5) the maxillary inter-premolar and inter-molar widths. The arch
      length-tooth size discrepancy was only calculated for subjects with no missing
      teeth. Palatal canine impaction occurred most frequently in subjects with a Class
      II division 2 malocclusion. There was an association between palatal canine
      impaction and anomalous lateral incisors (P = 0.01). The transverse arch
      dimension was significantly wider in the impaction group than in the comparison
      group (P < 0.01). There was no statistically significant difference in the
      mesiodistal width of maxillary teeth or in the arch length-tooth size discrepancy
      between the palatal canine impaction group and their matched comparisons (P >
      0.05). These results suggest that the presence of an 'excess palatal width' and
      anomalous lateral incisor may contribute to the aetiology of palatal canine
      impaction.

PMID- 15961571
TI  - Light curing time reduction: in vitro evaluation of new intensive light-emitting
      diode curing units.
AB  - The aim of the present in vitro study was to establish the minimum necessary
      curing time to bond stainless steel brackets (Mini Diamond Twin) using new,
      intensive, light-emitting diode (LED) curing units. Seventy-five bovine primary
      incisors were divided into five equal groups. A standard light curing adhesive
      (Transbond XT) was used to bond the stainless steel brackets using different
      lamps and curing times. Two groups were bonded using an intensive LED curing lamp
      (Ortholux LED) for 5 and 10 seconds. Two more groups were bonded using another
      intensive LED curing device (Ultra-Lume LED 5) also for 5 and 10 seconds.
      Finally, a high-output halogen lamp (Optilux 501) was used for 40 seconds to bond
      the final group, which served as a positive control. All teeth were fixed in hard
      acrylic and stored for 24 hours in water at 37 degrees C. Shear bond strength
      (SBS) was measured using an Instron testing machine. Weibull distribution and
      analysis of variance were used to test for significant differences. The SBS
      values obtained were significantly different between groups (P < 0.001). When
      used for 10 seconds, the intensive LED curing units achieved sufficient SBS,
      comparable with the control. In contrast, 5 seconds resulted in significantly
      lower SBS. The adhesive remnant index (ARI) was not significantly affected.A
      curing time of 10 seconds was found to be sufficient to bond metallic brackets to
      incisors using intensive LED curing units. These new, comparatively inexpensive,
      curing lamps seem to be an advantageous alternative to conventional halogen lamps
      for bonding orthodontic brackets.

PMID- 15961572
TI  - Numerical simulation of the biomechanical behaviour of multi-rooted teeth.
AB  - The elastic properties of the periodontal ligament (PDL) in eight multi-rooted
      teeth were examined in a combined experimental and numerical study in six
      minipigs. The initial tooth movement of the mandibular primary molars surrounded
      by the periodontium was registered three-dimensionally (3D) in an optomechanical
      measuring system. The dissections were then embedded in resin and cut in
      transverse sections. Based on these sections, 3D finite element (FE) models were
      constructed and numerically loaded with the same force systems as used in the
      experiment. The material behaviour of the PDL registered in the experiment was
      non-linear and could be approximated with a bilinear parameter set consisting of
      two Young's moduli, E1 and E2, and one ultimate strain, epsilon12, separating
      both elastic regimes. When a deficient congruence existed between the
      experimental and numerical force/deflection curves the material parameters were
      varied to obtain a satisfactory congruence. The material behaviour determined for
      these specimens delivered mean values of E1 = 0.05 MPa, E2 = 0.18 MPa and
      epsilon12 = 6.4 per cent for the elastic behaviour of the multi-rooted minipig
      teeth. There was no significant difference in the material parameters determined
      for specimens with two, four or six roots. The results were in close agreement
      with the material parameters of the PDL, determined in previous investigations of
      single-rooted human and pig teeth.

PMID- 15961573
TI  - Recolonization of mutans steptococci on teeth with orthodontic appliances after
      antimicrobial therapy.
AB  - The aim of the present study was to compare the recolonization pattern of mutans
      streptococci on densely colonized teeth with and without fixed orthodontic
      appliances after treatment with a 40 per cent chlorhexidine (CHX) varnish (EC 40,
      Explore). Healthy subjects free of carious lesions requiring fixed orthodontic
      appliance treatment but with high bacterial mutans streptococci saliva counts
      were recruited (n = 10). For baseline registration, plaque from buccal sites was
      sampled and cultivated on Dentocult strips. Following professional tooth
      cleaning, CHX varnish was applied to all teeth for 8 minutes. Subsequently,
      orthodontic brackets and bands were inserted in either the upper or lower arch.
      Eight weeks after varnish application the degree of recolonization with mutans
      streptococci was reassessed on the buccal sites. Statistical analysis showed that
      recolonization with mutans streptococci was significantly higher (P < 0.05) on
      teeth with orthodontic appliances. The results indicate that the use of fixed
      orthodontic appliances creates artificial environments suitable for the
      proliferation of mutans streptococci after CHX varnish suppression.

PMID- 15961574
TI  - Polarization of naive T cells into Th1 or Th2 by distinct cytokine-driven murine
      dendritic cell populations: implications for immunotherapy.
AB  - Dendritic cells (DCs) activate T cells and regulate their differentiation into T
      helper cell type 1 (Th1) and/or Th2 cells. To identify DCs with differing
      abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow
      progenitors in granulocyte macrophage-colony stimulating factor (GM), GM +
      interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations.
      The GM + IL-4 DCs expressed high levels of CD80/CD86 and major histocompatibility
      complex (MHC) class II and produced low levels of IL-12p70. GM and GM + IL-15 DCs
      expressed low levels of CD80/CD86 and MHC class II. The GM + IL-15 DCs produced
      high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only
      high levels of IL-12p70. Naive T cells stimulated with GM + IL-4 DCs secreted
      high levels of IL-4 and IL-5 in addition to IFN-gamma. In contrast, the GM + IL
      15 DCs induced higher IFN-gamma production by T cells with little or no Th2
      cytokines. GM DCs did not induce T cell polarization, despite producing large
      amounts of IL-12p70 following activation. A similar pattern of T cell activation
      was observed after in vivo administration of DCs. These data suggest that IL
      12p70 production alone, although necessary for Th1 differentiation, is not
      sufficient to induce Th1 responses. These studies have implications for the use
      of DC-based vaccines in immunotherapy of cancer and other clinical conditions.

PMID- 15961575
TI  - Effect of plasmid backbone modification by different human CpG motifs on the
      immunogenicity of DNA vaccine vectors.
AB  - DNA vaccines, in general, have been found to be poorly immunogenic in nonhuman
      primates and humans as compared with mice. As the immunogenicity of DNA plasmids
      relies, to a large extent, on the presence of CpG motifs as built in adjuvants,
      we addressed the issue of poor immunogenicity by inserting recently identified
      CpG oligonucleotides (ODN) optimal for human (K-type or D-type CpG ODN) into the
      backbone of plasmid VR1020. We found that plasmid DNA containing K-type CpG
      motifs or D-type CpG motifs significantly enhanced the up-regulation of surface
      molecules and production of interleukin-6 from human peripheral blood mononuclear
      cells (PBMC) and stimulated monocytes to develop into functionally mature
      dendritic cells (DC) compared with unmodified plasmid. Monocyte maturation into
      DC was through plasmacytoid DC present in the culture. It is interesting that the
      K-type CpG motif-modified plasmid stimulated significant levels of interferon
      (IFN)-gamma and IFN-alpha from human PBMC. Immunization of mice with D-type CpG
      motif-modified plasmid, encoding Plasmodium falciparum surface protein 25,
      yielded enhanced antigen-specific antibodies. Taken together, these results
      suggest that insertion of immunomodulatory human CpG motifs into plasmid DNA can
      improve immunogenicity of DNA vaccines.

PMID- 15961576
TI  - Maintenance of the CD40-related immunodeficient response in hyper-IgM B cells
      immortalized with a LMP1-regulated mini-EBV.
AB  - Our previous investigation of a patient (pt1) with non-X-linked hyper
      immunoglobulin M syndrome revealed a CD40-mediated defect in B cell activation
      that resulted in low CD23 expression and absence of germ-line transcription and
      class-switch recombination. These deficiencies were complemented in vitro by a
      high threshold of sustained signaling through CD40. To further analyze the
      signaling defect in pt1 B cells, two types of Epstein-Barr virus lymphoblastoid
      cell lines (LCLs) were generated that either constitutively expressed the viral
      transforming protein latent membrane protein-1 (LMP1; pt1-LCL) or expressed it
      under the control of a tet-inducible promoter (pt1-LCL(tet)). Because LMP1
      signals through the CD40 pathway, the pt1-LCL and pt1-LCL(tet) lines allow
      comparison of downstream functions in response to either constitutive LMP1
      signals or regulated LMP1 and CD40 signals. Immortalized pt1-LCLs were initially
      CD23(lo)/CD38(hi) and reverted to a CD23(hi)/CD38(lo) phenotype upon extended
      growth in culture, suggesting that the CD40 defect was reversed by selection
      and/or constitutive expression of LMP1. In contrast, pt1-LCL(tet) cells retained
      the CD23(lo)/CD38(hi) phenotype after extended periods of culture and failed to
      up-regulate CD23 in response to CD40 signals. Analysis of pt1-LCL(tet) cells in
      response to the CD40 signals in the presence or absence of LMP1 revealed that
      mitogenic activation resulted only from LMP1 and not CD40, indicating a
      difference in the response of pt1 B cells to these two distinct signals.
      Together, these data demonstrate that the pt1-LCL(tet) cells maintain the CD40
      related defect and provide a unique approach to study the independent effects of
      LMP1- and CD40-directed signals.

PMID- 15961577
TI  - Chemokine expression during development of fibrosis versus resolution in a murine
      model of granulomatous experimental autoimmune thyroiditis.
AB  - Severe granulomatous experimental autoimmune thyroiditis (G-EAT) in DBA/1 or
      CBA/J wild type (WT) mice at day 19 progresses to fibrosis by day 35, but severe
      G-EAT in DBA/1 interferon (IFN)-gamma-/- mice or less-severe G-EAT at day 19 in
      WT mice resolves by day 35. To study the role of chemokines in autoimmune
      diseases and fibrosis, profiles of chemokines and chemokine receptors were
      analyzed in DBA/1 WT versus IFN-gamma-/- and CBA/J thyroids, which have distinct
      outcomes of autoimmune inflammation. Gene expression of CXC chemokine ligand 1
      (CXCL1) and CXC chemokine receptor 2 (CXCR2) paralleled neutrophil infiltration
      and thyrocyte destruction in DBA/1 WT or CBA/J thyroids, and gene expression of
      CC chemokine ligand 11 (CCL11), CCL8, and CC chemokine receptor 3 paralleled
      eosinophil infiltration in IFN-gamma-/- thyroids. Gene and protein expression of
      CXCL10, CXCL9, and CXCR3 was significantly lower in IFN-gamma-/- compared with
      DBA/1 WT thyroids. Moreover, immunostaining showed that CXCL10 was expressed by
      thyrocytes and inflammatory cells, and strong expression of CXCL10 by thyrocytes
      was as early as day 7. High expression of CCL2 was only observed in severely
      destroyed DBA/1 WT or CBA/J thyroids, which would develop fibrosis. Thus, the
      differential expression of chemokines may direct distinct cellular populations in
      DBA/1 WT versus IFN-gamma-/- thyroids. Up-regulation of CXCL10 by thyrocytes
      suggests its role in regulating the recruitment of specific subsets of activated
      lymphocytes to the thyroid during autoimmune inflammation. The early expression
      of CXCL1, CXCL10, and CCL2 may suggest their involvement in the initiation and
      perpetuation of disease in severe G-EAT thyroids, which progress to fibrosis.

PMID- 15961578
TI  - Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)
      1 expression in human mononuclear leukocytes.
AB  - Thrombin, the key enzyme of the coagulation cascade, exerts cellular effects
      through activation of the protease-activated receptors (PARs). Interleukin (IL)
      10, besides its anti-inflammatory properties, is considered a major denominator
      of the immunosuppressive effect during human endotoxemia. We have recently shown
      that thrombin inhibits IL-12 production in human mononuclear cells and that such
      inhibition is accompanied by IL-10 up-regulation. To our knowledge, there are no
      data available to show that thrombin mediates IL-10 production by its
      interactions with PAR-1. We here report that human alpha-thrombin enhances IL-10
      expression in human peripheral blood mononuclear cells and in established
      monocytic cell lines and that this up-regulation requires PAR-1 expression. The
      use of proteolytically inactive thrombin reveals that such enhancement requires
      thrombin proteolytic activity. Addition of PAR-1 agonist peptides, such as
      SFLLRN, results in a significant increase of IL-10 production. PAR-1 expression
      is required for thrombin-induced IL-10 production, as shown by experiments
      performed with antisense or sense PAR-1 oligonucleotides. Treatment with thrombin
      or SFLLRN of monocytic cell lines, such as U937 and Mono Mac-6, results in an
      increased IL-10 production. This suggests that the observed IL-10 up-regulation
      may be the result of a direct interaction with monocytes. The observation that
      thrombin-mediated up-regulation of IL-10 may require the expression of the PAR-1
      receptor identifies a new, functional link between inflammation and coagulation.
      Our results may also contribute to better design therapeutic strategies to treat
      several disorders, characterized by the presence of inflammatory as well as
      coagulant responses.

PMID- 15961580
TI  - Epidemiologic approaches to disasters: reducing our vulnerability.

PMID- 15961579
TI  - Profiling dendritic cell maturation with dedicated microarrays.
AB  - Dendritic cell (DC) maturation is the process by which immature DC in the
      periphery differentiate into fully competent antigen-presenting cells that
      initiate the T cell response. However, DC respond to many distinct maturation
      stimuli, and different types of mature DC induce qualitatively different T cell
      responses. As DC maturation involves the coordinated regulation of hundreds of
      genes, comprehensive assessment of DC maturation status would ideally involve
      monitoring the expression of all of these transcripts. However, whole-genome
      microarrays are not well-suited for routine phenotyping of DC, as the vast
      majority of genes represented on such chips are not relevant to DC biology, and
      their cost limits their use for most laboratories. We therefore developed a DC
      dedicated microarray, or "DC Chip", incorporating probes for 121 genes up
      regulated during DC maturation, 93 genes down-regulated during maturation, 14 DC
      specific genes, and 90 other genes with known or probable immune functions. These
      microarrays were used to study the kinetics of DC maturation and the differences
      in maturation profiles among five healthy donors after stimulation with tumor
      necrosis factor-alpha + polyI:C. Results obtained with the DC Chip were
      consistent with flow cytometry, enzyme-linked immunosorbent assay, and real-time
      polymerase chain reaction, as well as previously published data. Furthermore, the
      coordinated regulation of a cluster of genes (indoleamine dioxygenase,
      kynureninase, kynurenine monoxygenase, tryptophanyl tRNA synthetase, and 3
      hydroxyanthranilate 3,4-dioxygenase) involved in tryptophan metabolism was
      observed. These data demonstrate the use of the DC Chip for monitoring the
      molecular processes involved in the orientation of the immune response by DC.

PMID- 15961581
TI  - CTLA-4 gene polymorphisms and susceptibility to type 1 diabetes mellitus: a HuGE
      Review and meta-analysis.
AB  - The authors performed a meta-analysis of 33 studies examining the association of
      type 1 diabetes mellitus with polymorphisms in the cytotoxic T-lymphocyte
      associated antigen-4 (CTLA-4) gene, including the A49G (29 comparisons), C(-318)T
      (three comparisons), and (AT)n microsatellite (six comparisons) polymorphisms.
      The studies included 5,637 cases of type 1 diabetes and 6,759 controls (4,775 and
      5,829, respectively, for analysis of the A49G polymorphism). The random-effects
      odds ratio for the *G (Ala) allele versus the *A (Thr) allele was 1.45 (95%
      confidence interval (CI): 1.28, 1.65), with significant between-study
      heterogeneity (p < 0.001). The effect size tended to be higher in type 1 diabetes
      cases with age of onset <20 years (odds ratio (OR) = 1.61), and there was a
      significant association between the presence of glutamic acid decarboxylase-65
      autoantibodies and the *G allele among type 1 diabetes cases (OR = 1.49). Larger
      studies showed more conservative results (p = 0.011). After exclusion of studies
      with fewer than 150 subjects and studies with significant deviation from Hardy
      Weinberg equilibrium in the controls, the summary odds ratio was 1.40 (95% CI:
      1.28, 1.54). Available data showed no strong association for the 106-base-pair
      allele of the microsatellite polymorphism (OR = 0.99, 95% CI: 0.64, 1.55) or the
      *T allele of the C(-318)T polymorphism (OR = 0.92, 95% CI: 0.45, 1.89). This meta
      analysis demonstrates that the CTLA-4*G genotype is associated with type 1
      diabetes.

PMID- 15961583
TI  - The relation between calcium intake and body composition in a Dutch population:
      The Amsterdam Growth and Health Longitudinal Study.
AB  - To investigate whether dietary calcium intake is related to body mass index and
      the sum of four skinfolds among subjects in the Amsterdam Growth and Health
      Longitudinal Study (the Netherlands), the authors followed a cohort of men and
      women from age 13 years in 1977 to age 36 years in 2000. Longitudinal linear
      regression analyses were performed with generalized estimating equations in
      continuous and categorical models, with adjustment for possible confounders.
      Results showed that calcium intake during adolescence is a weak predictor of
      calcium intake in adulthood. In this population, only a slight indication was
      found of a weak inverse relation of calcium intake with body composition. No
      differences were observed between the middle (800-1,200 mg/day) and high (>1,200
      mg/day) groups of calcium intake, suggesting a threshold of approximately 800
      mg/day above which calcium intake has no additional beneficial effect on body
      composition.

PMID- 15961582
TI  - In utero exposure to background levels of polychlorinated biphenyls and cognitive
      functioning among school-age children.
AB  - Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. In
      utero exposure to background levels of PCBs has been associated with intellectual
      impairment among children in most, but not all, studies. The authors evaluated
      prenatal PCB exposure in relation to cognitive test (intelligence quotient (IQ))
      scores on the Wechsler Intelligence Scale for Children at age 7 years. Pregnant
      women were recruited from 12 US study centers from 1959 to 1965, and their
      children were followed until age 7 years (the Collaborative Perinatal Project).
      Third trimester serum was analyzed for PCBs in 1997-1999 for 732 women selected
      at random and for an additional 162 women whose children had either a low or a
      high IQ score. The PCB-IQ association was examined in multivariate models. Among
      those in the lowest exposure category (<1.25 microg of PCB/liter of serum), the
      fully adjusted mean IQ score was 93.6 (standard error: 1.8); among those in the
      highest category (> or =5 microg of PCB/liter), the mean IQ was 97.6 (standard
      error: 1.2); and overall the increase in IQ per unit increase in PCB level
      (microg/liter) was 0.22 (95% confidence interval: -0.28, 0.71). In these data, in
      utero exposure to background levels of PCBs was not associated with lower IQ at
      age 7 years.

PMID- 15961584
TI  - Ankle-brachial index and subclinical cardiac and carotid disease: the multi
      ethnic study of atherosclerosis.
AB  - The authors studied associations between ankle-brachial index (ABI) and
      subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis.
      Participants included 3,458 women (average age = 62.6 years) and 3,112 men
      (average age = 62.8 years) who were free of clinically evident cardiovascular
      disease. Measurements included ABI, carotid artery intima-media thickness, and
      coronary artery calcium assessed with computed tomography. Five ABI categories
      were defined: <0.90 (definite peripheral arterial disease (PAD)), 0.90-0.99
      (borderline ABI), 1.00-1.09 (low-normal ABI), 1.10-1.29 (normal ABI), and > or
      =1.30 (high ABI). Compared with that in men with normal ABI, significantly higher
      internal carotid artery intima-media thickness was observed in men with definite
      PAD (1.58 vs. 1.09; p < 0.001), borderline ABI (1.33 vs. 1.09; p < 0.001), and
      low-normal ABI (1.18 vs. 1.09; p < 0.001) after adjustment for confounders. Fully
      adjusted odds ratios for a coronary artery calcium score greater than 20
      decreased across progressively higher ABI categories in both women (2.85
      (definite PAD), 1.27 (borderline ABI), 1.11 (low-normal ABI), 1.00 (normal ABI;
      referent), and 0.78 (high ABI); p for trend = 0.0002) and men (3.26 (definite
      PAD), 1.72 (borderline ABI), 1.14 (low-normal ABI), 1.00 (normal ABI; referent),
      and 1.43 (high ABI); p for trend = 0.0002). These findings indicate excess
      coronary and carotid atherosclerosis at ABI values below 1.10 (men) and 1.00
      (women) and may imply increased risk of cardiovascular events in persons with
      borderline and low-normal ABI.

PMID- 15961585
TI  - Body mass index and incident ischemic heart disease in South Korean men and
      women.
AB  - Asian populations have a higher body fat percentage for a given body mass index
      (BMI) than Caucasians. However, little information is available on the
      association of BMI with ischemic heart disease (IHD) incidence in Asians at low
      BMI levels. The authors prospectively evaluated the association of BMI (weight
      (kg)/height m2) with IHD incidence over 9 years of follow-up (1993-2001) among
      133,740 South Korean adults (89,050 men, 44,690 women) who participated in the
      1990 and 1992 examinations of the Korea Medical Insurance Corporation Study.
      Average BMI at baseline was 23.4 (standard deviation, 2.3) in men and 22.3
      (standard deviation, 2.3) in women. After multivariate adjustment, there was a
      14% (95% confidence interval: 12, 16) increased risk of incident IHD per unit of
      increase in BMI. This trend was also observed within the range considered normal
      by Western standards, and a BMI of 24-<25 was associated with an IHD hazard ratio
      of 2.01 (95% confidence interval: 1.32, 3.05) in comparison with a BMI of 18-<19.
      The association of BMI with IHD in this cohort of relatively young South Korean
      men and women was progressive over the range of BMI values, with no threshold of
      change in risk and no indication of a U-shaped relation at low BMI levels.

PMID- 15961586
TI  - Ethnicity, education, and blood pressure in Cuba.
AB  - The causes of variation in hypertension risk by ethnicity and educational level
      are not well understood. To gain further insight into this issue in a
      nonindustrialized country, a population-based sample of 1,667 persons aged 15-74
      years was recruited in Cienfuegos, Cuba. In this 2001-2002 study, interviewers
      classified 29% of participants as Black or mulatto and 71% as White. Educational
      attainment was stratified at the median number of school years. Compared with
      White women, non-White women had higher blood pressures (3.0/1.7, systolic blood
      pressure/diastolic blood pressure) and a higher prevalence of hypertension (24%,
      95% confidence interval: 20, 28 vs. 15%, 95% confidence interval: 12, 18). Among
      men, no differences in blood pressure were observed by ethnicity. Men with a
      lower level of education had a 14% lower risk of hypertension compared with men
      above the median. However, women with a lower level of education had a 24%
      increase in risk. The effect of education was equally strong among Whites alone
      and when occupation was used for stratification. No variation was observed for
      body mass index or self-reported health behaviors by ethnicity or education. The
      narrower ethnic gradient in hypertension prevalence than seen in North America
      and the gender-specific social status effect, in the context of relatively equal
      living conditions, suggest that the influence of psychosocial stressors may be
      specific to cultural contexts.

PMID- 15961587
TI  - Is the association between socioeconomic position and coronary heart disease
      stronger in women than in men?
AB  - The association between socioeconomic position and health is generally believed
      to be weaker among women than men. However, gender differences in the relation
      between socioeconomic position and coronary heart disease have not been evaluated
      in a representative sample of the US population. The authors examined this
      association in the First National Health and Nutrition Examination Survey (1971
      1993), a longitudinal, representative study of the US population (n = 6,913).
      Information on educational attainment, household income, and covariates was
      derived from the baseline interview, and that on incident coronary heart disease
      was obtained from hospital records/death certificates over 22 years of follow-up.
      Cox's proportional hazards models showed that education and income were inversely
      associated with incident coronary heart disease in age-only and multivariate
      models. Risk associated with education varied by gender (p = 0.01), with less
      than high school education associated with stronger risk of coronary heart
      disease in women (relative risk = 2.15, 95% confidence interval: 1.46, 3.17) than
      in men (relative risk = 1.58, 95% confidence interval: 1.18, 2.12) in age
      adjusted models. Low education was associated with greater social and
      psychological risks for women than men; however, metabolic risks largely
      explained gender differences in the educational gradient in coronary heart
      disease.

PMID- 15961588
TI  - Short-term oral contraceptive use and the risk of epithelial ovarian cancer.
AB  - Oral contraceptive (OC) use has been consistently linked to a reduction in
      ovarian cancer in a dose-dependent fashion. Whether short-term OC use is
      protective remains controversial. In 1994-1998 in the Delaware Valley of
      Pennsylvania, the authors examined the association between short-term OC use and
      ovarian cancer in a population-based case-control study comparing 608 incident
      epithelial ovarian cancer cases with 926 community controls. Using unconditional
      logistic regression and adjusting for known confounders, they found a significant
      reduction in ovarian cancer risk for women who had used OCs for < or =6 months
      (odds ratio = 0.73, 95% confidence interval: 0.54, 0.99). This protective effect
      was observed in only that group who had used OCs for < or =6 months and stopped
      because of side effects (odds ratio = 0.59, 95% confidence interval: 0.40, 0.87
      for side effects and odds ratio = 0.91, 95% confidence interval: 0.60, 1.37 for
      non-side-effects). Women who used OCs for >6 months were at a reduced risk
      independent of their reason for stopping. Results were similar when stratifying
      by parity and hormone therapy use. Thus, OC use for as little as 6 months
      provides significant protection against ovarian cancer risk, protection that
      appears limited to those women who stop using OCs because of side effects.
      Mediating factors may reflect endogenous hormone levels, OC metabolism, or OC
      bioactivity.

PMID- 15961589
TI  - Intensity of smoking and smoking cessation in relation to risk of cataract
      extraction: a prospective study of women.
AB  - The authors investigated the association of smoking and smoking cessation with
      the incidence of cataract extraction in a population-based prospective cohort
      study. A total of 34,595 women aged 49-83 years in the Swedish Mammography Cohort
      were followed from September 1997 through June 2002. Information on smoking,
      diet, and other lifestyle factors was collected through a self-administered
      questionnaire. A total of 2,128 cases of age-related cataract extraction were
      identified. Relative risks were estimated as rate ratios using Cox proportional
      hazards models. The authors observed a significant dose-response association
      between intensity of smoking and risk of cataract extraction (among current
      smokers, p for trend = 0.02; among past smokers, p for trend = 0.0002). After
      cessation of smoking, the risk decreased with time. Among women with a moderate
      lifetime smoking intensity (6-10 cigarettes/day), the relative risk was not
      significantly different from the risk among never smokers 10 years after smoking
      cessation. Among women who had smoked more intensively (>10 cigarettes/day),
      after 20 years of nonsmoking the increased risk became small and no longer
      statistically significant in comparison with never smokers (for trend over time,
      p < 0.0001). This prospective study confirmed smoking as a risk factor for
      cataract, with a dose response for smoking intensity. Smoking cessation predicts
      reduced risk over time, but a longer period of time is needed with a higher
      smoking intensity.

PMID- 15961590
TI  - Are the acute effects of particulate matter on mortality in the National
      Morbidity, Mortality, and Air Pollution Study the result of inadequate control
      for weather and season? A sensitivity analysis using flexible distributed lag
      models.
AB  - Time-series studies have linked daily variations in nonaccidental deaths with
      daily variations in ambient particulate matter air pollution, while controlling
      for qualitatively larger influences of weather and season. Although time-series
      analyses typically include nonlinear terms for weather and season, questions
      remain as to whether models to date have completely controlled for these
      important predictors. In this paper, the authors use two flexible versions of
      distributed lag models to control extensively for the confounding effects of
      weather and season. One version builds on the current approach to controlling for
      weather, while the other version offers a new approach. The authors conduct a
      comprehensive sensitivity analysis of the particulate matter-mortality relation
      by applying these methods to the recently updated National Morbidity, Mortality,
      and Air Pollution Study database that comprises air pollution, weather, and
      mortality time series from 1987 to 2000 for 100 US cities. They combine city
      specific estimates of the short-term effects of particulate matter on mortality
      using a Bayesian hierarchical model. They conclude that, within the broad classes
      of models considered, national average estimates of particulate matter relative
      risk are consistent with previous estimates from this study and are robust to
      model specification for weather and seasonal confounding.

PMID- 15961591
TI  - Dynamic models of meningococcal carriage, disease, and the impact of serogroup C
      conjugate vaccination.
AB  - Much interest has surrounded the use of conjugate vaccines in recent years, with
      the development of vaccines against disease caused by Haemophilus influenzae type
      b, Neisseria meningitidis, and Streptococcus pneumoniae. These vaccines offer the
      potential for safe and effective disease control, but some questions remain,
      particularly regarding the duration and mechanisms of protection and the longer
      term impact of vaccination on carriage. In this paper, the authors use data on
      immunization with serogroup C meningococcal conjugate vaccines in England and
      Wales to develop and apply a mathematical model to investigate the direct and
      indirect (herd immunity) effects of a conjugate vaccine program. A realistic, age
      structured, dynamic model was developed and parameterized and was fitted to
      epidemiologic data from England and Wales. The effects of a range of vaccine
      strategies, including hypothetical scenarios, were investigated. The basic
      reproduction number was estimated to be 1.36. Catch-up vaccination targeting
      teenagers generated substantial herd immunity and was important in controlling
      disease rapidly. The results were sensitive to changes in the assumptions
      regarding the method of vaccine action, particularly duration of protection and
      efficacy of vaccination against carriage acquisition. This model can be used to
      help predict the potential impact of vaccine strategies both in the United
      Kingdom and elsewhere.

PMID- 15961592
TI  - Radiological evaluation of sinus lift operation: what the general radiologist
      needs to know.
AB  - This article provides an overview of the sinus lift operation, including
      radiographic evaluation of the procedure. Plain radiographs such as dental or
      panoramic radiographs have conventionally been used to measure the bone volume in
      the operation site, but full three-dimensional assessment of the region before
      and after the sinus lift operation is advisable both to allow planning of the
      lift and to see the results of it. The general radiologists sometimes
      misinterpret the graft material used in sinus lift cases as odontogenic tumour or
      some other pathology. The aim of this article is to put an end to this wrong
      interpretation and to familiarize the general radiologist with pre-operative and
      post-operative imaging of sinus lift cases.

PMID- 15961593
TI  - Software for automated application of a reference-based method for a posteriori
      determination of the effective radiographic imaging geometry.
AB  - OBJECTIVES: Presentation and validation of software developed for automated and
      accurate application of a reference-based algorithm (reference sphere method:
      RSM) inferring the effective imaging geometry from quantitative radiographic
      image analysis. METHODS: The software uses modern pattern recognition and
      computer vision algorithms adapted for the particular application of automated
      detection of the reference sphere shadows (ellipses) with subpixel accuracy. It
      applies the RSM algorithm to the shadows detected, thereby providing three
      dimensional Cartesian coordinates of the spheres. If the three sphere centres do
      not lie on one line, they uniquely determine the imaging geometry. Accuracy of
      the computed coordinates is investigated in a set of 28 charge-coupled device
      (CCD)-based radiographs of two human mandible segments produced on an optical
      bench. Each specimen contained three reference spheres (two different radii
      r1=1.5 mm, r2=2.5 mm). True sphere coordinates were assessed with a manually
      operated calliper. Software accuracy was investigated for a weighted and
      unweighted algebraic ellipse-fitting algorithm. RESULTS: The critical depth- (z-)
      coordinates revealed mean absolute errors ranging between 1.1+/-0.7 mm
      (unweighted version; r=2.5 mm) and 1.4+/-1.4 mm (weighted version, r=2.5 mm),
      corresponding to mean relative errors between 5% and 6%. Outliers resulted from
      complete circular dense structure superimposition and one obviously deformed
      reference sphere. CONCLUSIONS: The software provides information fundamentally
      important for the image formation and geometric image registration, which is a
      crucial step for three-dimensional reconstruction from > or =2 two-dimensional
      views.

PMID- 15961594
TI  - Thallium-201 chloride (Tl-201) accumulation and Na+/K+-ATPase expression in
      tumours of the head and neck.
AB  - OBJECTIVES: The purpose of this report was to evaluate the relationship between
      the tumour retention index of thallium-201 chloride (Tl-201) scintigraphy and the
      Na+/K+-ATPase expression in tumours of the head and neck. METHODS: Tl-201
      scintigraphy was performed in 146 patients (129 with malignant tumours, ten with
      benign tumours and seven with inflammation). The tumour retention index was
      obtained from the early and delayed dynamic Tl-201 scans. The Na+/K+-ATPase
      expression was evaluated immunohistochemically in 61 of 129 patients with
      malignant tumour. Furthermore, another 22 patients with benign tumour were
      evaluated immunohistochemically as a benign control. Comparison of the
      correlations between the grade of histopathological differentiation of tumour,
      the tumour retention index of Tl-201 scintigraphy and the Na+/K+-ATPase
      expression was performed. RESULTS: The grade of histopathological differentiation
      of tumour, the tumour retention index of Tl-201 scintigraphy and the expression
      of Na+/K+-ATPase showed a good correlation indicating that Na+/K+-ATPase plays an
      important role in transportation for Tl-201 to go through the tumour cell
      membrane. CONCLUSIONS: Na+/K+-ATPase is one of the most important factors for Tl
      201 accumulation in tumour.

PMID- 15961596
TI  - Survey of dental radiological practice in Turkey.
AB  - OBJECTIVES: The aim of this study was to determine the dentist's knowledge about
      dose reduction techniques, radiographic equipment and quality of dental
      radiographic service in general dental practice in Turkey. METHODS: The survey
      was performed on 636 dentists who attended the 11th International Congress
      organized by the Turkish Dental Association. Information on the demographic
      characteristics of the dentists, radiographic equipment, techniques and
      processing they used and radiation protection was obtained with a 32 point
      questionnaire. RESULTS: The respondents' knowledge concerning the technical
      details of their equipment was limited, with 512 (86.9%) not knowing the
      kilovoltage peak (kVp) of their machine. Only 34 (5.5%) respondents reported
      having rectangular collimators. The dentists had little knowledge about the speed
      of film they used. D-speed film was the most preferred one with 21.6%. Fifty
      eight (10.2%) dentists used E-speed film and the F-speed film was used only by 13
      (2.3%) dentists. The most preferred technique (62%) for periapical radiography
      was the bisecting angle technique. Four hundred and eighty five (82.5%) of the
      dentists reported that they took the radiographs by themselves. CONCLUSIONS: In
      the present study, the results indicate that for minimizing any unnecessary
      radiation, attempts should be made to improve dentists' knowledge about radiation
      dose reduction techniques.

PMID- 15961595
TI  - A trial for histopathological subclassification of papillary cystadenoma
      lymphomatosum by 99Tcm-pertechnetate in a patient with multiple bilateral lesions
      of the parotid glands.
AB  - OBJECTIVES: The purpose of this report was to evaluate the possibility of
      subclassification of papillary cystadenoma lymphomatosum (PCL) with 99Tc(m)
      pertechnetate. METHODS: A patient with multiple bilateral PCLs in the parotid
      glands was examined by using 99Tc(m)-pertechnetate. RESULTS: All PCLs of the
      present case, which were diagnosed as the subtype-II histopathologically, showed
      similar radioactive indexes in scintigraphy (the mean radioactive index = 3.62),
      although tumours were different in size. The mean radioactive index corresponded
      well with that from four cases of subtype-II of our previous report (the mean
      radioactive index = 3.84). CONCLUSIONS: The results of the present report suggest
      a possibility of histopathological subclassification of PCLs into subtypes by
      99Tc(m)-pertechnetate scintigraphy.

PMID- 15961597
TI  - Audit for extraoral radiographic examinations in a digital department.
AB  - OBJECTIVES: To investigate whether extraoral radiographs requested by clinicians
      were actually viewed by the clinicians after recording. METHODS: Digital
      extraoral images recorded at the radiology department were tracked over a 1-year
      period. Digital images are communicated to the clinical departments through our
      Picture Archiving and Communication System and may be viewed at any computer
      which houses the image display and enhancement software "DigiView". DigiView
      keeps track of user actions, among others where and when an image is opened. An
      image was defined as viewed if it had been opened in DigiView within 3 months
      after it had been recorded. The number of opened and non-opened images was
      calculated in relation to the referring clinical departments/units in the dental
      school. RESULTS: 2374 digital extraoral images were requested by the clinical
      departments. Two-thirds of these images were requested from the orthodontic
      department. Twenty-two percent (n=346) of their requested images were not opened.
      The distribution of non-opened images for the other clinical departments was:
      oral surgery=3% (18 images); periodontology=17% (1 image); treatment planning=33%
      (1 image); prosthetic=5% (6 images); county=21% (8 images) and oral
      physiology=23% (6 images). Panoramic images constituted the majority (58%) of non
      opened images. Twenty-six percent of the images were opened once, 15% were opened
      twice and 41% were opened three times or more. CONCLUSIONS: Digital imaging
      offers new possibilities for audit compared with conventional film radiography.
      It seems that custom in some disciplines rules the referral of patients to
      radiographic examination and that this may lead to over-prescription.

PMID- 15961598
TI  - A precise receptor-positioning device for subtraction radiography, based on cross
      arch stabilization.
AB  - OBJECTIVES: To devise and test for reproducibility a new patient-beam alignment
      device for subtraction radiography. METHODS: A rigid, cross-arch bar was used
      with bite-registration material. A modified Rinn XCP rod and ring were firmly
      attached to the bar and were placed in contact with the X-ray cone. The receptor
      was held by a slot in the bar. Duplicate sets (n=8 pairs) of digital radiographs
      were made with a modified, calibrated DenOptix photostimulable phosphor system.
      Image pairs were registered and compared for geometrical and intensity errors by
      means of quantitative subtraction radiography. The reproducibility of patient
      beam alignment for each pair was determined by measuring spatial errors at
      alveolar crest edges and by comparing magnifications. Intensity errors measured
      at two predetermined regions of alveolar bone were used to estimate corresponding
      bone-mass errors. RESULTS: Misalignment at the alveolar crest was generally <1
      pixel (0.085 mm), and everywhere < or =0.25 mm. The magnification was constant
      within a relative standard deviation of 0.13% (n=8). Trabecular features were
      generally invisible or barely visible in subtraction images. The standard
      deviation of intensity errors was 1.07% (n=16). This corresponds to a change in
      bone mass of approximately 2% or less. CONCLUSION: The device has potential for
      clinical population studies in which the goal is to detect small changes in bone
      mass and alveolar-crest height. It is convenient to use and comfortable for
      patients. Because of the cross-arch design, patient-beam alignment is expected to
      be relatively insensitive to bite-registration errors, tooth movement, and tooth
      loss.

PMID- 15961599
TI  - MR images mimic disc after discectomy.
AB  - MRI of a 30-year-old woman 1 year after discectomy showed a residual disc-like
      tissue. The observation was initially confusing, but a close comparison of pre-
      and post-operative images suggested that the inferior wall of the anterior joint
      capsule had migrated superiorly after the removal of the disc and mimicked a
      residual disc on the follow-up MR images.

PMID- 15961600
TI  - Multiple idiopathic external apical root resorption: report of four cases.
AB  - Multiple idiopathic external root resorption is an unusual condition that may
      present in a cervical or an apical form. In this article, we review the published
      literature relating to multiple idiopathic external apical root resorption and
      present four clinical cases. We consider the aetiology of this condition and
      discuss the various treatment options.

PMID- 15961601
TI  - An unusual tonsillolithiasis in a patient with chronic obstructive sialoadenitis.
AB  - Concretions in the tonsil or peritonsillar area are an infrequent entity in
      clinical practice. Some patients have no symptoms or they can present with fetor
      oris or odynophagia. The lesions are often detected incidentally during
      radiographic examination. This pathology can be related to lithiasis in other
      regions of body. The authors describe a tonsillolith accidentally detected in a
      patient with a lithiasis of left submandibular gland. We review published cases
      of tonsilloliths and analyse the causes of stone formation in peritonsillar and
      tonsil regions.

PMID- 15961602
TI  - Dentomaxillofacial imaging in Proteus syndrome.
AB  - Proteus syndrome is a rare condition that involves atypical growth of the bones,
      skin and head and a variety of other symptoms. Only a few authors have reported
      on the craniofacial manifestations so far. The authors present a case of a 7-year
      old girl with Proteus syndrome in which the facial skeleton showed unilateral
      overgrowth. The analysis of the radiological evaluation revealed a bialveolar
      prognathism, a skeletal class III, a dolicocephalic growth pattern and a left
      convex face scoliosis. On the left side, the lesser wing of the sphenoid was
      elevated and the ethmoidal cell complex was hypertrophic. The left ramus and body
      of the mandible were enlarged. The asymmetric dental development with a
      precocious dental age on the affected side was the most striking feature on the
      panoramic view. Early diagnosis and therapy depend on clinical evaluation and
      imaging. Therefore, further evaluations on the craniofacial features of patients
      with Proteus syndrome are necessary in order to establish a list of
      characteristic symptoms.

PMID- 15961603
TI  - Nasolabial cyst with radiographic contrast medium: report of two cases.
AB  - Two cases are presented of a nasolabial cyst (NC) on which a radiographic
      contrast medium was used in order to define the real extension of the lesion. Use
      of contrast is important for visualizing the definite extensions of NC primarily
      in cases when plain radiographs may not show any detectable changes and CT can
      not be used.

PMID- 15961604
TI  - Trifid mandibular nerve canal.

PMID- 15961605
TI  - Effectiveness of mask and helmet interfaces to deliver noninvasive ventilation in
      a human model of resistive breathing.
AB  - The helmet, a transparent latex-free polyvinyl chloride cylinder linked by a
      metallic ring to a soft collar that seals the helmet around the neck, has been
      recently proposed as an effective alternative to conventional face mask to
      deliver pressure support ventilation (PSV) during noninvasive ventilation in
      patients with acute respiratory failure. We tested the hypothesis that mechanical
      characteristics of the helmet (large internal volume and high compliance) might
      impair patient-ventilator interactions compared with standard face mask.
      Breathing pattern, CO(2) clearance, indexes of inspiratory muscle effort and
      patient-ventilator asynchrony, and dyspnea were measured at different levels of
      PSV delivered by face mask and helmet in six healthy volunteers before (load-off)
      and after (load-on) application of a linear resistor. During load-off, no
      differences in breathing pattern and inspiratory muscle effort were found. During
      load-on, the use of helmet to deliver pressure support increased inspiratory
      muscle effort and patient-ventilator asynchrony, worsened CO(2) clearance, and
      increased dyspnea compared with standard face mask. Autocycled breaths accounted
      for 12 and 25% of the total minute ventilation and for 10 and 23% of the total
      inspiratory muscle effort during mask and helmet PSV, respectively. We conclude
      that PSV delivered by helmet interface is less effective in unloading inspiratory
      muscles compared with PSV delivered by standard face mask. Other ventilatory
      assist modes should be tested to exploit to the most the potential benefits
      offered by the helmet.

PMID- 15961606
TI  - Efficiency of the normal human diaphragm with hyperinflation.
AB  - We evaluated an index of diaphragm efficiency (Eff(di)), diaphragm power output
      (Wdi) relative to electrical activation, in five healthy adults during tidal
      breathing at usual end-expiratory lung volume (EELV) and diaphragm length (L(di
      ee)) and at shorter L(di ee) during hyperinflation with expiratory positive
      airway pressure (EPAP). Measurements were repeated with an inspiratory threshold
      (7.5 cmH(2)O) plus resistive (6.5 cmH(2)O.l(-1).s) load. Wdi was the product of
      mean inspiratory transdiaphragmatic pressure (DeltaPdi(mean)), diaphragm volume
      displacement measured fluoroscopically, and 1/inspiratory duration (Ti(-1)).
      Diaphragm activation, measured with esophageal electrodes, was quantified by
      computing root-mean-square values (RMS(di)). With EPAP, 1) EELV increased [mean
      r(2) = 0.91 (SD 0.01)]; 2) in four subjects, L(di ee) decreased [mean r(2) = 0.85
      (SD 0.07)] and mean Eff(di) decreased 34% per 10% decrease in L(di ee) (P <
      0.001); and 3) in one subject, gastric pressure at EELV increased two- to
      threefold, L(di ee) was unchanged or increased, and Eff(di) increased at two of
      four levels of EPAP (P < or = 0.006, ANOVA). Inspiratory loading increased Wdi (P
      = 0.003) and RMS(di) (P = 0.004) with no change in Eff(di) (P = 0.63) or its
      relationship with L(di ee). Eff(di) was more accurate in defining changes in L(di
      ee) [(true positives + true negatives)/total = 0.78 (SD 0.13)] than
      DeltaPdi(mean).RMS(di)(-1), RMS(di), or DeltaPdi(mean).Ti (all <0.7, P < or =
      0.05, without load). Thus Eff(di) was principally a function of L(di ee)
      independent of inspiratory loading, behavior consistent with muscle force-length
      velocity properties. We conclude that Eff(di), measured during tidal breathing
      and in the absence of expiratory muscle activity at EELV, is a valid and accurate
      measure of diaphragm contractile function.

PMID- 15961607
TI  - Effects of dietary phytoestrogens on cardiac remodeling secondary to chronic
      volume overload in female rats.
AB  - Previously, we demonstrated that intact female rats fed a standard rodent diet
      containing soybean products exhibit essentially no adverse left ventricular (LV)
      remodeling in response to aortocaval fistula-induced chronic volume overload. We
      hypothesized that phytoestrogenic compounds in the diet contributed to the female
      cardioprotection. To test this hypothesis, four groups of female rats were
      studied: sham-operated (Sham) and fistula (Fist) rats fed a diet with [P(+)] or
      without [P(-)] phytoestrogens. Eight weeks postfistula, systolic and diastolic
      cardiac function was assessed by using a blood-perfused, isolated heart
      preparation. High-phytoestrogen diet had no effect on body, heart, and lung
      weights, or cardiac function in Sham rats. Fistula groups developed LV
      hypertrophy, which was not reduced by dietary phytoestrogens [1,184 +/- 229 mg
      Fist-P(-) and 1,079 +/- 199 mg Fist-P(+) vs. 620 +/- 47 mg for combined Sham
      groups, P < 0.05]. Unstressed LV volume increased in Fist-P(-) rats (428 +/- 16
      vs. 300 +/- 14 microl Sham, P < 0.0001), but it was not different from Sham for
      Fist-P(+) animals (286 +/- 17 microl). Fist-P(-) rats developed increased
      ventricular compliance (5.3 +/- 0.8 vs. 2.3 +/- 0.3 microl/mmHg Sham, P < 0.01),
      whereas Fist-P(+) rats had no change in compliance (2.8 +/- 0.4 mul/mmHg).
      Intrinsic ventricular contractility was maintained in the Fist-P(+) rats, but it
      was reduced (P < 0.001) in the Fist-P(-) rats [systolic pressure-volume slope:
      1.04 +/- 0.03, 0.60 +/- 0.06, and 0.99 +/- 0.08 mmHg/microl, for Fist-P(+), Fist
      P(-), and Sham, respectively]. These data indicate that dietary phytoestrogens
      contribute significantly to female cardioprotection against volume overload
      induced adverse ventricular remodeling and that studies evaluating gender
      differences in cardiovascular remodeling must consider the influence of dietary
      phytoestrogens.

PMID- 15961608
TI  - Early time course of myocardial electrical impedance during acute coronary artery
      occlusion in pigs, dogs, and humans.
AB  - Changes in myocardial electrical impedance (MEI) and physiological end points
      have been correlated during acute ischemia. However, the importance of MEI's
      early time course is not clear. This study evaluates such significance, by
      comparing the temporal behavior of MEI during acute total occlusion of the left
      anterior descending coronary artery in anesthetized humans, dogs, and pigs. Here,
      interspecies differences in three MEI parameters (baseline, time to plateau
      onset, and plateau value normalized by baseline) were evaluated using Kruskal
      Wallis ANOVA and post hoc tests (P < 0.05). Noteworthy differences in the MEI
      time to plateau onset were observed: In dogs, MEI ischemic plateau was reached
      after 46.3 min (SD 12.9) min of occlusion, a significantly longer period compared
      with that of pigs and humans [4.7 (SD 1.2) and 4.1 min (SD 1.9), respectively].
      However, no differences could be observed between both animal species regarding
      the normalized MEI ischemic plateau value (15.3% (SD 4.7) in pigs, vs. 19.6% (SD
      2.6) in dogs). For all studied MEI parameters, only swine values resembled those
      of humans. The severity of myocardial supply ischemia, resulting from coronary
      artery occlusion, is known to be dependent on collateral flow. Thus, because dogs
      possess a well-developed collateral system (unlike humans or pigs), they have
      shown superior resistance to occlusion of a coronary artery. Here, the early MEI
      time course after left anterior descending coronary artery occlusion, represented
      by the time required to reach ischemic plateau, was proven to reflect such
      interspecies differences.

PMID- 15961609
TI  - Lack of response to all-trans retinoic acid supplementation in adult dogs
      following left pneumonectomy.
AB  - We showed previously that removing 55-58% of the lung by right pneumonectomy (R
      PNX) in adult dogs triggers compensatory growth of the remaining lung, but
      removing 42-45% of the lung by left PNX (L-PNX) does not. We also showed that,
      following R-PNX, supplemental all-trans retinoic acid (RA) selectively enhances
      alveolar capillary endothelial cell volume (Yan X, Bellotto DJ, Foster DJ,
      Johnson RL, Jr., Hagler HH, Estrera AS, and Hsia CC. J Appl Physiol 96: 1080
      1089, 2004). We hypothesized that RA supplementation might enhance compensation
      following L-PNX and tested this hypothesis by administering RA (2 mg.kg(-1).day(
      1), 4 days/wk) or placebo orally to litter-matched adult foxhounds for 4 mo
      following L-PNX. Resting lung function was measured under anesthesia. Air and
      tissue volumes of the remaining lung were assessed by high-resolution computed
      tomography scan and by detailed postmortem morphometric analysis of the fixed
      lung. There was no significant difference in resting lung function, lung volume,
      alveolar structure, or septal ultrastructure between RA and placebo treatment
      groups. We conclude that RA supplementation does not induce post-PNX compensatory
      lung growth in the absence of existing cellular growth activities initiated by
      other primary signals.

PMID- 15961610
TI  - 5,6-EET-induced contraction of intralobar pulmonary arteries depends on the
      activation of Rho-kinase.
AB  - The mechanism mediating epoxyeicosatrienoic acid (EET)-induced contraction of
      intralobar pulmonary arteries (PA) is currently unknown. EET-induced contraction
      of PA has been reported to require intact endothelium and activation of the
      thromboxane/endoperoxide (TP) receptor. Because TP receptor occupation with the
      thromboxane mimetic U-46619 contracts pulmonary artery via Rho-kinase activation,
      we examined the hypothesis that 5,6-EET-induced contraction of intralobar rabbit
      pulmonary arteries is mediated by a Rho-kinase-dependent signaling pathway. In
      isolated rings of second-order intralobar PA (1-2 mm OD) at basal tension, 5,6
      EET (0.3-10 microM) induced increases in active tension that were inhibited by Y
      27632 (1 microM) and HA-1077 (10 microM), selective inhibitors of Rho-kinase
      activity. In PA in which smooth muscle intracellular Ca(2+) concentration
      ([Ca(2+)](i)) was increased with KCl (25 mM) to produce a submaximal contraction,
      5,6-EET (1 microM) induced a contraction that was 7.0 +/- 1.6 times greater than
      without KCl. 5,6-EET (10 microM) also contracted beta-escin permeabilized PA in
      which [Ca(2+)](i) was clamped at a concentration resulting in a submaximal
      contraction. Y-27632 inhibited the 5,6-EET-induced contraction in permeabilized
      PA. 5,6-EET (10 microM) increased phosphorylation of myosin light chain (MLC),
      increasing the ratio of phosphorylated MLC/total MLC from 0.10 +/- 0.03 to 0.30
      +/- 0.02. Y-27632 prevented this increase in MLC phosphorylation. These data
      suggest that 5,6-EET induces contraction in intralobar PA by increasing Rho
      kinase activity, phosphorylating MLC, and increasing the Ca(2+) sensitivity of
      the contractile apparatus.

PMID- 15961611
TI  - Habitual exercise program protects murine intestinal, skeletal, and cardiac
      muscles against aging.
AB  - Aging and aerobic exercise are two conditions known to interfere with health and
      quality of life, most likely by inducing oxidative stress to the organism. We
      studied the effects of aging on the morphological and functional properties of
      skeletal, cardiac, and intestinal muscles and their corresponding oxidative
      status in C57BL/6 mice and investigated whether a lifelong moderate exercise
      program would exert a protective effect against some deleterious effects of
      aging. As expected, aged animals presented a significant reduction of physical
      performance, accompanied by a decrease of gastrocnemius cross-sectional area and
      cardiac hypertrophy. However, most interesting was that aging dramatically
      interfered with the intestinal structure, causing a significant thickening of the
      ileum muscular layer. Senescent intestinal myocytes displayed many mitochondria
      with disorganized cristae and the presence of cytosolic lamellar corpuscles.
      Lipid peroxidation of ileum and gastrocnemius muscle, but not of the heart,
      increased in aged mice, thus suggesting enhanced oxidative stress. With exception
      of the intestinal muscle responsiveness, animals submitted to a daily session of
      60 min, 5 days/wk, at 13 up to 21 m/min of moderate running in treadmill during
      animal life span exhibited a reversion of all the observed aging effects on
      intestinal, skeletal, and heart muscles. The introduction of this lifelong
      exercise protocol prevented the enhancement of lipid peroxidation and sarcopenia
      and also preserved cellular and ultracellular structures of the ileum. This is
      the first time that the protective effect of a lifelong regular aerobic physical
      activity against the deleterious effects of aging on intestinal muscle was
      demonstrated.

PMID- 15961612
TI  - Expression of phospholemman and its association with Na+-K+-ATPase in skeletal
      muscle: effects of aging and exercise training.
AB  - Phospholemman (PLM) is a recently identified accessory protein of the Na(+)-K(+)
      ATPase (NKA), with a high level of expression in skeletal muscle. The objectives
      of this study are to characterize the PLM in skeletal muscle and to test the
      hypothesis that, as an accessory protein of NKA, expression of PLM and its
      association with the alpha-subunits of NKA is regulated during aging and with
      exercise training. PLM was characterized in skeletal muscle of 6- and 16-mo-old
      sedentary middle-aged rats (Ms), and the effects of aging and exercise training
      were studied in Ms, 29-mo-old sedentary senescent, and 29-mo-old treadmill
      exercised senescent rats. Expression of PLM was muscle-type dependent, and
      immunofluorescence study showed that PLM distributed predominantly on the
      sarcolemmal membrane of the muscle fibers. Anti-PLM antibody reduced activity of
      NKA, and thus PLM appears to be required for NKA to express its full activity in
      skeletal muscle. Expression of PLM was not altered with aging but increased after
      exercise training. Coimmunoprecipitation studies demonstrated that PLM associates
      with both the alpha(1)- and alpha(2)-subunit isoforms of NKA. Compared with Ms
      rats, levels of PLM-associated alpha(1)-subunit increased in 29-mo-old sedentary
      senescent rats, and treadmill exercise has a tendency to partially reverse it.
      There was no significant change in PLM-associated alpha(2)-subunit with age, and
      exercise training has a tendency to increase that level. It is concluded that, in
      skeletal muscle, PLM appears to be a protein integral to the NKA complex and that
      PLM has the potential to modulate NKA in an isoform-specific and muscle type
      dependent manner in aging and after exercise training.

PMID- 15961613
TI  - Lack of age-related decreases in basal whole leg blood flow in resistance-trained
      men.
AB  - Reductions in basal leg blood flow have been implicated in the pathogenesis of
      metabolic syndrome and functional impairment in humans. We tested the hypothesis
      that reductions in basal whole leg blood flow with age are either absent or
      attenuated in those who perform regular strength training. A total of 104
      normotensive men aged 20-34 yr (young) and 35-65 yr (middle aged), who were
      either sedentary or resistance trained, were studied. Mean and diastolic blood
      pressures were higher (P < 0.05-0.001) in the middle-aged compared with the young
      men, but there were no significant differences between the sedentary and
      resistance-trained groups. In the sedentary group, basal whole leg blood flow
      (duplex Doppler ultrasound) and vascular conductance were lower ( approximately
      30 and approximately 38%, respectively; P < 0.01) in the middle-aged compared
      with the young men. There were no such age-related differences in the resistance
      trained group. In the young men, basal whole leg blood flow and vascular
      conductance were not different between the two activity groups, but, in the
      middle-aged men, they were higher ( approximately 35 and approximately 36%,
      respectively; P < 0.01) in the resistance-trained men than in the sedentary men.
      When blood flow and vascular conductance were expressed relative to the leg
      muscle mass, the results were essentially the same. We concluded that the age
      related reduction in basal whole leg blood flow is absent in resistance-trained
      men. These results suggest that resistance training may favorably influence leg
      perfusion in aging humans, independent of its impact on leg muscle mass.

PMID- 15961614
TI  - Sympathetic nervous activity decreases during head-down bed rest but not during
      microgravity.
AB  - We tested the hypothesis that sympathoadrenal activity in humans is low during
      spaceflight and that this effect can be simulated by head-down bed rest (HDBR).
      Platelet norepinephrine and epinephrine were measured as indexes of long-term
      changes in sympathoadrenal activity. Ten normal healthy subjects were studied
      before and during HDBR of 2-wk duration, as well as during an ambulatory study
      period of a similar length. Platelet norepinephrine concentrations (half-life = 2
      days) were studied in five cosmonauts, 2 wk before launch, within 12 h after
      landing after 11-12 days of flight, and at least 2 wk after return to Earth.
      Because of the long half-life of platelet norepinephrine, data obtained early
      after landing would still reflect the microgravity state. Platelet norepinephrine
      decreased markedly during HDBR (P < 0.001), whereas there were no significant
      changes when subjects were ambulatory. Platelet epinephrine did not change during
      HDBR. During microgravity, platelet norepinephrine and epinephrine increased in
      four of the five cosmonauts. Platelet norepinephrine concentrations expressed in
      percentage of preflight and pre-HDBR values, respectively, were significantly
      different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs.
      60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also
      significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet
      norepinephrine and epinephrine response during spaceflight flight is most likely
      related to the concomitant decrease in plasma volume. HDBR cannot be applied to
      simulate changes in sympathoadrenal activity during microgravity.

PMID- 15961615
TI  - Assessing historical exposure is like solving a mystery.

PMID- 15961616
TI  - Silica: deja vu all over again?

PMID- 15961617
TI  - Long term effects of air pollution in Europe.

PMID- 15961618
TI  - Use of history science methods in exposure assessment for occupational health
      studies.
AB  - AIMS: To show the power of history science methods for exposure assessment in
      occupational health studies, using the dry cleaning industry in Denmark around
      1970 as the example. METHODS: Exposure data and other information on exposure
      status were searched for in unconventional data sources such as the Danish
      National Archives, the Danish Royal Library, archives of Statistics Denmark, the
      National Institute of Occupational Health, Denmark, and the Danish Labor
      Inspection Agency. Individual census forms were retrieved from the Danish
      National Archives. RESULTS: It was estimated that in total 3267 persons worked in
      the dry cleaning industry in Denmark in 1970. They typically worked in small
      shops with an average size of 3.5 persons. Of these, 2645 persons were considered
      exposed to solvents as they were dry cleaners or worked very close to the dry
      cleaning process, while 622 persons were office workers, drivers, etc in shops
      with 10 or more persons. It was estimated that tetrachloroethylene constituted
      85% of the dry cleaning solvent used, and that a shop would normally have two
      machines using 4.6 tons of tetrachloroethylene annually. CONCLUSION: The history
      science methods, including retrieval of material from the Danish National
      Archives and a thorough search in the Royal Library for publications on dry
      cleaning, turned out to be a very fruitful approach for collection of exposure
      data on dry cleaning work in Denmark. The history science methods proved to be a
      useful supplement to the exposure assessment methods normally applied in
      epidemiological studies.

PMID- 15961619
TI  - Mortality in the UK industrial silica sand industry: 1. Assessment of exposure to
      respirable crystalline silica.
AB  - AIMS: To develop a job-exposure matrix (JEM) from personal and static respirable
      crystalline silica (RCS) measurements in UK industrial silica sand workers.
      METHODS: A total of 2429 personal and 583 static RCS dust samples were collected
      using cyclone samplers at seven UK quarries between 1978 and 2000. These data
      were combined, and analysis of variance using general linear models was used to
      evaluate the effect of quarry, job, and year on RCS concentrations, and
      facilitate the creation of five quarry and three time categories with similar
      exposure levels by comparing the least-square GM RCS concentrations. RESULTS: The
      overall geometric mean (GM) RCS concentration was 0.09 mg/m3 (geometric standard
      deviation 3.9). Silica flour and dry job categories tended to have the highest
      RCS exposure and 13.3% of all samples exceeded the UK maximum exposure level of
      0.3 mg/m3. RCS levels generally decreased over time. CONCLUSIONS: Data have been
      collected and used to develop a JEM for UK industrial silica sand workers between
      1978 and 2000. Although there were some limitations in the data and certain
      assumptions were made, the use of available data to estimate exposure
      quantitatively is an improvement over the use of qualitative and surrogate
      measures of exposure. The continual collection of dust measurements in the
      industry is essential to facilitate the exploration of exposure-response
      relations that may exist between silica and silicosis, lung cancer, and other
      diseases.

PMID- 15961620
TI  - Mortality in the UK industrial silica sand industry: 2. A retrospective cohort
      study.
AB  - AIMS: To evaluate the mortality experience of a cohort of employees in the UK
      silica sand industry exposed to respirable crystalline silica (RCS). METHODS: A
      retrospective cohort mortality study followed all workers to 2001 with at least
      one year's employment at one of seven UK silica sand producing quarries between
      1950 and 1986. Each worker was assigned a job category and cumulative exposure to
      RCS was estimated using a job-exposure matrix. RESULTS: A total of 764 deaths
      were identified in 2703 cohort members. The overall mortality rate for the cohort
      was lower than would be expected in the general population. Mortality from
      circulatory and respiratory disease was also less than expected, but death due to
      pneumoconiosis was slightly raised (two deaths). Mortality from all cancers was
      slightly decreased. Mortality was not raised in any job category. Cancer
      mortality was raised at one quarry due to a significant increase in lung
      (standardised mortality rate (SMR) 162.0, 95% CI 113.5 to 224.3) and bladder (SMR
      366.5, 95% CI 167.6 to 695.7) cancers. Mortality from lung cancer and other
      causes did not show a trend with cumulative exposure to RCS. CONCLUSIONS: This
      study did not show any consistent relation between RCS exposure (in the absence
      of other known carcinogens) and the development of lung cancer. This contrasts
      with a number of studies that have shown positive findings in similar and related
      industries.

PMID- 15961621
TI  - Twenty five year mortality and air pollution: results from the French PAARC
      survey.
AB  - AIMS AND METHODS: Long term effects of air pollution on mortality were studied in
      14,284 adults who resided in 24 areas from seven French cities when enrolled in
      the PAARC survey (air pollution and chronic respiratory diseases) in 1974. Daily
      measurements of sulphur dioxide, total suspended particles, black smoke, nitrogen
      dioxide, and nitric oxide were made in 24 areas for three years (1974-76). Cox
      proportional hazards models controlling for individual confounders (smoking,
      educational level, body mass index, occupational exposure) were applied, and
      frailty models used to take into account spatial correlation. Indicators of air
      pollution were the mean concentration. RESULTS: Models were run before and after
      exclusion of six area monitors influenced by local traffic (NO/NO2 >3 in ppb).
      After exclusion of these areas, analyses showed that adjusted risk ratios (95%
      CI) for TSP, BS, NO2, and NO for non-accidental mortality were 1.05 (1.02 to
      1.08), 1.07 (1.03 to 1.10), 1.14 (1.03 to 1.25), and 1.11 (1.05 to 1.17) for 10
      microg/m3 respectively. Consistent patterns for lung cancer and cardiopulmonary
      causes were observed. CONCLUSIONS: Urban air pollution assessed in the 1970s was
      associated with increased mortality over 25 years in France.

PMID- 15961622
TI  - Cancer incidence in the Swedish leather tanning industry: updated findings 1958
      99.
AB  - AIMS: To assess how a 10 year extension of the follow up period affected cancer
      incidence in the Swedish leather tanning cohort. METHODS: A cohort of 2027
      tannery workers (of which 482 were women) who had been employed for at least one
      year between 1900 and 1989 at one of three Swedish leather tanneries, was
      established. The start of observation varied between 1958 and 1966 for the three
      plants. Through linkage with the Swedish Cancer Registry, incident cancer cases
      were recorded up to 1999. Cause specific expected cancer incidence was calculated
      for 1958-99 based on calendar year, sex, and five year age group specific
      incidence rates for the counties where the plants had been located. Altogether
      56,022 person-years at risk were generated. RESULTS: A total of 351 incident
      cancer cases were observed compared to 302 expected, which resulted in an
      increased standardised incidence ratio (SIR) of 1.16 (95% CI 1.04 to 1.29). An
      enhanced risk for prostate cancer was observed (SIR 1.44, 95% CI 1.10 to 1.86),
      mainly attributable to the later part of the observation period (1990-99). In
      this updated analysis the previously observed risk excess for soft tissue
      sarcomas was no longer significant (SIR 2.62, 95% CI 0.96 to 5.70). For multiple
      myelomas and sinonasal cancer the slight non-significant excesses remained, still
      based on very few cases. CONCLUSIONS: The increased risk for prostate cancer in
      the present study might be a chance finding, but is noteworthy, since it is in
      acccordance with the finding of increased SIR for prostate cancer among leather
      workers in another recent Swedish study. Moreover, excess risks for prostate
      cancer among farmers have been reported, indicating pesticides as possible
      causative agents. Leather tanners have also been exposed to pesticides.

PMID- 15961623
TI  - Age at exposure to ionising radiation and cancer mortality among Hanford workers:
      follow up through 1994.
AB  - BACKGROUND: Studies of workers at the plutonium production factory in Hanford, WA
      have led to conflicting conclusions about the role of age at exposure as a
      modifier of associations between ionising radiation and cancer. AIMS: To evaluate
      the influence of age at exposure on radiation risk estimates in an updated follow
      up of Hanford workers. METHODS: A cohort of 26 389 workers hired between 1944 and
      1978 was followed through 1994 to ascertain vital status and causes of death.
      External radiation dose estimates were derived from personal dosimeters. Poisson
      regression was used to estimate associations between mortality and cumulative
      external radiation dose at all ages, and in specific age ranges. RESULTS: A total
      of 8153 deaths were identified, 2265 of which included cancer as an underlying or
      contributory cause. Estimates of the excess relative risk per Sievert (ERR/Sv)
      for cumulative radiation doses at all ages combined were negative for all cause
      and leukaemia and positive for all cancer and lung cancer. Cumulative doses
      accrued at ages below 35, 35-44, and 45-54 showed little association with
      mortality. For cumulative dose accrued at ages 55 and above (10 year lag), the
      estimated ERR/Sv for all cancers was 3.24 (90% CI: 0.80 to 6.17), primarily due
      to an association with lung cancer (ERR/Sv: 9.05, 90% CI: 2.96 to 17.92).
      CONCLUSIONS: Associations between radiation and cancer mortality in this cohort
      are primarily a function of doses at older ages and deaths from lung cancer. The
      association of older age radiation exposures and cancer mortality is similar to
      observations from several other occupational studies.

PMID- 15961624
TI  - Appropriate use of personal protective equipment among healthcare workers in
      public sector hospitals and primary healthcare polyclinics during the SARS
      outbreak in Singapore.
AB  - BACKGROUND: Singapore was affected by an outbreak of severe acute respiratory
      syndrome (SARS) from 25 February to 31 May 2003, with 238 probable cases and 33
      deaths. AIMS: To study usage of personal protective equipment (PPE) among three
      groups of healthcare workers (HCWs: doctors, nurses, and administrative staff),
      to determine if the appropriate PPE were used by the different groups and to
      examine the factors that may determine inappropriate use. METHODS: A self
      administered questionnaire survey of 14,554 HCWs in nine healthcare settings,
      which included tertiary care hospitals, community hospitals, and polyclinics, was
      carried out in May-July 2003. Only doctors, nurses, and clerical staff were
      selected for subsequent analysis. RESULTS: A total of 10 236 valid questionnaires
      were returned (70.3% response); 873 doctors, 4404 nurses, and 921 clerical staff
      were studied. A total of 32.5% of doctors, 48.7% of nurses, and 77.1% of the
      administrative staff agreed that paper and/or surgical masks were "useful in
      protecting from contracting SARS". Among this group, 23.6% of doctors and 42.3%
      of nurses reported working with SARS patients. The view that a paper and/or
      surgical mask was adequate protection against SARS was held by 33.3% of doctors
      and 55.9% of nurses working at the A&E unit, 30.5% of doctors and 49.4% of nurses
      from medical wards, and 27.5% of doctors and 37.1% of nurses from intensive care
      units. Factors which predicted for agreement that paper and/or surgical masks
      were protective against SARS, included HCW's job title, reported contact with
      SARS patients, area of work, and Impact Events Scale scores. CONCLUSION: A
      variety of factors determine appropriate use of personal protective equipment by
      HCWs in the face of a major SARS outbreak.

PMID- 15961626
TI  - Breast cancer risk among Finnish cabin attendants: a nested case-control study.
AB  - BACKGROUND: Earlier studies have found increased breast cancer risk among female
      cabin crew. This has been suggested to reflect lifestyle factors (for example,
      age at first birth), other confounding factors (for example, age at menarche), or
      occupational factors such as exposure to cosmic radiation and circadian rhythm
      alterations due to repeated jet lag. AIMS: To assess the contribution of
      occupational versus lifestyle and other factors to breast cancer risk among cabin
      attendants in Finland. METHODS: A standardised self-administered questionnaire on
      demographic, occupational, and lifestyle factors was given to 1041 cabin
      attendants. A total of 27 breast cancer cases and 517 non-cases completed the
      questionnaire. Breast cancer diagnoses were confirmed through the Finnish Cancer
      Registry. Exposure to cosmic radiation was estimated based on self-reported
      flight history and timetables. A conditional logistic regression model was used
      for analysis. RESULTS: In the univariate analysis, family history of breast
      cancer (OR = 2.67, 95% CI: 1.00 to 7.08) was the strongest determinant of breast
      cancer. Of occupational exposures, sleep rhythm disruptions (OR = 1.72, 95% CI:
      0.70 to 4.27) were positively related and disruption of menstrual cycles (OR =
      0.71, 95% CI: 0.26 to 1.96) negatively related to breast cancer. However, both
      associations were statistically non-significant. Cumulative radiation dose (OR =
      0.99, 95% CI: 0.83 to 1.19) showed no effect on breast cancer. CONCLUSIONS:
      Results suggest that breast cancer risk among Finnish cabin attendants is related
      to well established risk factors of breast cancer, such as family history of
      breast cancer. There was no clear evidence that the three occupational factors
      studied affected breast cancer risk among Finnish flight attendants.

PMID- 15961625
TI  - A randomised controlled trial of postural interventions for prevention of
      musculoskeletal symptoms among computer users.
AB  - AIMS: To examine the effect of two workstation and postural interventions on the
      incidence of musculoskeletal symptoms among computer users. METHODS: Randomised
      controlled trial of two distinct workstation and postural interventions (an
      alternate intervention and a conventional intervention) among 376 persons using
      computer keyboards for more than 15 hours per week. The incidence of
      neck/shoulder symptoms and hand/arm symptoms during six months of follow up among
      individuals in the intervention groups was compared to the incidence in computer
      users who did not receive an intervention (comparison group). For individuals in
      the intervention groups, study staff adjusted workstations, where possible, and
      trained individuals to assume the intervention postures. Individuals reported
      musculoskeletal symptoms in a weekly diary. Participants who reported discomfort
      intensity of 6 or greater on a 0-10 visual analogue scale or who reported
      musculoskeletal symptoms requiring use of analgesic medication were considered
      symptomatic. RESULTS: There were no significant differences in the incidence of
      musculoskeletal symptoms among the three intervention groups. Twenty two (18.5%)
      participants in the alternate intervention group, 25 (20.2%) in the conventional
      intervention group, and 25 (21.7%) in the comparison group developed incident arm
      or hand symptoms. Thirty eight (33.3%) participants in the alternate intervention
      group, 36 (31.0%) in the conventional intervention group, and 33 (30.3%) in the
      comparison group developed incident neck or shoulder symptoms. Compliance with
      all components of the intervention was attained for only 25-38% of individuals,
      due mainly to the inflexibility of workstation configurations. CONCLUSIONS: This
      study provides evidence that two specific workplace postural interventions are
      unlikely to reduce the risk of upper extremity musculoskeletal symptoms among
      computer users.

PMID- 15961628
TI  - Regression modelling and other methods to control confounding.

PMID- 15961629
TI  - 142Nd evidence for early (>4.53 Ga) global differentiation of the silicate Earth.
AB  - New high-precision samarium-neodymium isotopic data for chondritic meteorites
      show that their 142Nd/144Nd ratio is 20 parts per million lower than that of most
      terrestrial rocks. This difference indicates that most (70 to 95%) of Earth's
      mantle is compositionally similar to the incompatible element-depleted source of
      mid-ocean ridge basalts, possibly as a result of a global differentiation 4.53
      billion years ago (Ga), within 30 million years of Earth's formation. The
      complementary enriched reservoir has never been sampled and is probably located
      at the base of the mantle. These data influence models of Earth's compositional
      structure and require revision of the timing of global differentiation on Earth's
      Moon and Mars.

PMID- 15961627
TI  - Identifying public water facilities with low spatial variability of disinfection
      by-products for epidemiological investigations.
AB  - BACKGROUND AND AIMS: Epidemiological studies of disinfection by-products (DBPs)
      and reproductive outcomes have been hampered by misclassification of exposure. In
      most epidemiological studies conducted to date, all persons living within the
      boundaries of a water distribution system have been assigned a common exposure
      value based on facility-wide averages of trihalomethane (THM) concentrations.
      Since THMs do not develop uniformly throughout a distribution system, assignment
      of facility-wide averages may be inappropriate. One approach to mitigate this
      potential for misclassification is to select communities for epidemiological
      investigations that are served by distribution systems with consistently low
      spatial variability of THMs. METHODS AND RESULTS: A feasibility study was
      conducted to develop methods for community selection using the Information
      Collection Rule (ICR) database, assembled by the US Environmental Protection
      Agency. The ICR database contains quarterly DBP concentrations collected between
      1997 and 1998 from the distribution systems of 198 public water facilities with
      minimum service populations of 100,000 persons. Facilities with low spatial
      variation of THMs were identified using two methods; 33 facilities were found
      with low spatial variability based on one or both methods. Because brominated
      THMs may be important predictors of risk for adverse reproductive outcomes, sites
      were categorised into three exposure profiles according to proportion of
      brominated THM species and average TTHM concentration. The correlation between
      THMs and haloacetic acids (HAAs) in these facilities was evaluated to see whether
      selection by total trihalomethanes (TTHMs) corresponds to low spatial variability
      for HAAs. TTHMs were only moderately correlated with HAAs (r = 0.623).
      CONCLUSIONS: Results provide a simple method for a priori selection of sites with
      low spatial variability from state or national public water facility datasets as
      a means to reduce exposure misclassification in epidemiological studies of DBPs.

PMID- 15961630
TI  - Marked decline in atmospheric carbon dioxide concentrations during the Paleogene.
AB  - The relation between the partial pressure of atmospheric carbon dioxide (pCO2)
      and Paleogene climate is poorly resolved. We used stable carbon isotopic values
      of di-unsaturated alkenones extracted from deep sea cores to reconstruct pCO2
      from the middle Eocene to the late Oligocene (approximately 45 to 25 million
      years ago). Our results demonstrate that pCO2 ranged between 1000 to 1500 parts
      per million by volume in the middle to late Eocene, then decreased in several
      steps during the Oligocene, and reached modern levels by the latest Oligocene.
      The fall in pCO2 likely allowed for a critical expansion of ice sheets on
      Antarctica and promoted conditions that forced the onset of terrestrial C4
      photosynthesis.

PMID- 15961631
TI  - Crystal structure of human toll-like receptor 3 (TLR3) ectodomain.
AB  - Toll-like receptors (TLRs) play key roles in activating immune responses during
      infection. The human TLR3 ectodomain structure at 2.1 angstroms reveals a large
      horseshoe-shaped solenoid assembled from 23 leucine-rich repeats (LRRs).
      Asparagines conserved in the 24-residue LRR motif contribute extensive hydrogen
      bonding networks for solenoid stabilization. TLR3 is largely masked by
      carbohydrate, but one face is glycosylation-free, which suggests its potential
      role in ligand binding and oligomerization. Highly conserved surface residues and
      a TLR3-specific LRR insertion form a homodimer interface in the crystal, whereas
      two patches of positively charged residues and a second insertion would provide
      an appropriate binding site for double-stranded RNA.

PMID- 15961633
TI  - The fight of the decade.

PMID- 15961632
TI  - Genome-scale identification of nucleosome positions in S. cerevisiae.
AB  - The positioning of nucleosomes along chromatin has been implicated in the
      regulation of gene expression in eukaryotic cells, because packaging DNA into
      nucleosomes affects sequence accessibility. We developed a tiled microarray
      approach to identify at high resolution the translational positions of 2278
      nucleosomes over 482 kilobases of Saccharomyces cerevisiae DNA, including almost
      all of chromosome III and 223 additional regulatory regions. The majority of the
      nucleosomes identified were well-positioned. We found a stereotyped chromatin
      organization at Pol II promoters consisting of a nucleosome-free region
      approximately 200 base pairs upstream of the start codon flanked on both sides by
      positioned nucleosomes. The nucleosome-free sequences were evolutionarily
      conserved and were enriched in poly-deoxyadenosine or poly-deoxythymidine
      sequences. Most occupied transcription factor binding motifs were devoid of
      nucleosomes, strongly suggesting that nucleosome positioning is a global
      determinant of transcription factor access.

PMID- 15961634
TI  - Italian science. Abstentions scuttle drive to liberalize Italy's embryo laws.

PMID- 15961636
TI  - Geochemistry. New geochemical benchmark changes everything on Earth.

PMID- 15961635
TI  - Scientific publishing. Society bars papers from Iranian authors.

PMID- 15961637
TI  - Molecular biology. Nucleosomes help guide yeast gene activity.

PMID- 15961638
TI  - Intellectual property. U.S. patent reform begins long journey through Congress.

PMID- 15961639
TI  - Infectious diseases. Turf war halts Spain's foot-and-mouth disease studies.

PMID- 15961640
TI  - Astronomy. Extrasolar planets get smaller and (possibly) harder.

PMID- 15961641
TI  - Genetics. Jumping DNA mixes it up in the developing brain.

PMID- 15961642
TI  - Biomedical policy. House approves 0.5% raise for NIH, comments on database.

PMID- 15961643
TI  - Earth science. The story of O2.

PMID- 15961644
TI  - Earth science. A better atmosphere for life.

PMID- 15961645
TI  - American Astronomical Society meeting. A sprawling Andromeda Galaxy startles and
      puzzles observers.

PMID- 15961646
TI  - American Astronomical Society meeting. Snapshots from the meeting.

PMID- 15961647
TI  - American Astronomical Society meeting. A rocky landing for Deep Impact?

PMID- 15961648
TI  - American Society of Gene Therapy meeting. Retroviral vectors: a double-edged
      sword.

PMID- 15961649
TI  - American Society of Gene Therapy meeting. Smart vector restores liver enzyme.

PMID- 15961650
TI  - Space exploration. Private mission aims to give solar sails their day in the sun.

PMID- 15961651
TI  - Retraction.

PMID- 15961652
TI  - Reassessing U.S. coral reefs.

PMID- 15961653
TI  - Written in our genes?

PMID- 15961654
TI  - Comment on "Inflammatory exposure and historical changes in human life-spans".

PMID- 15961656
TI  - Comment on "The ocean sink for anthropogenic CO2".

PMID- 15961658
TI  - Plant science. GRAS genes and the symbiotic green revolution.

PMID- 15961659
TI  - Archaeology. Glassmaking in Bronze-Age Egypt.

PMID- 15961661
TI  - Climate. Uncertainty in hurricanes and global warming.

PMID- 15961660
TI  - Macroevolution. Seeds of diversity.

PMID- 15961662
TI  - Energetics of load carrying in Nepalese porters.
AB  - Nepalese porters routinely carry head-supported loads equal to 100 to 200% of
      their body weight (Mb) for many days up and down steep mountain footpaths at high
      altitudes. Previous studies have shown that African women carry head-supported
      loads of up to 60% of their Mb far more economically than army recruits carrying
      equivalent loads in backpacks. Here we show that Nepalese porters carry heavier
      loads even more economically than African women. Female Nepalese porters, for
      example, carry on average loads that are 10% of their Mb heavier than the maximum
      loads carried by the African women, yet do so at a 25% smaller metabolic cost.

PMID- 15961663
TI  - Late Bronze Age glass production at Qantir-Piramesses, Egypt.
AB  - It has been uncertain whether the glass produced during the Late Bronze Age (LBA)
      originated in Egypt or Mesopotamia. Here we present evidence for the production
      of glass from its raw materials in the eastern Nile Delta during the LBA. Glass
      was made in workshops that were separate from where the production of objects
      took place. The initial melting of the raw materials to semi-finished glass was
      done at temperatures of 900 degrees to 950 degrees C, followed by coloration and
      ingot production at 1000 degrees to 1100 degrees C.

PMID- 15961664
TI  - Quantum interference device made by DNA templating of superconducting nanowires.
AB  - The application of single molecules as templates for nanodevices is a promising
      direction for nanotechnology. We used a pair of suspended DNA molecules as
      templates for superconducting two-nanowire devices. Because the resulting wires
      are very thin, comparable to the DNA molecules themselves, they are susceptible
      to thermal fluctuations typical for one-dimensional superconductors and exhibit a
      nonzero resistance over a broad temperature range. We observed resistance
      oscillations in these two-nanowire structures that are different from the usual
      Little-Parks oscillations. Here, we provide a quantitative explanation for the
      observed quantum interference phenomenon, which takes into account strong phase
      gradients created in the leads by the applied magnetic field.

PMID- 15961665
TI  - Spectral signatures of hydrated proton vibrations in water clusters.
AB  - The ease with which the pH of water is measured obscures the fact that there is
      presently no clear molecular description for the hydrated proton. The mid
      infrared spectrum of bulk aqueous acid, for example, is too diffuse to establish
      the roles of the putative Eigen (H3O+) and Zundel (H5O2+) ion cores. To expose
      the local environment of the excess charge, we report how the vibrational
      spectrum of protonated water clusters evolves in the size range from 2 to 11
      water molecules. Signature bands indicating embedded Eigen or Zundel limiting
      forms are observed in all of the spectra with the exception of the three- and
      five-membered clusters. These unique species display bands appearing at
      intermediate energies, reflecting asymmetric solvation of the core ion. Taken
      together, the data reveal the pronounced spectral impact of subtle changes in the
      hydration environment.

PMID- 15961666
TI  - Dilution of the northern North Atlantic Ocean in recent decades.
AB  - Declining salinities signify that large amounts of fresh water have been added to
      the northern North Atlantic Ocean since the mid-1960s. We estimate that the
      Nordic Seas and Subpolar Basins were diluted by an extra 19,000 +/- 5000 cubic
      kilometers of freshwater input between 1965 and 1995. Fully half of that
      additional fresh water-about 10,000 cubic kilometers-infiltrated the system in
      the late 1960s at an approximate rate of 2000 cubic kilometers per year. Patterns
      of freshwater accumulation observed in the Nordic Seas suggest a century time
      scale to reach freshening thresholds critical to that portion of the Atlantic
      meridional overturning circulation.

PMID- 15961667
TI  - Secondary evolutionary escalation between brachiopods and enemies of other prey.
AB  - The fossil record of predation indicates that attacks on Paleozoic brachiopods
      were very rare, especially compared to those on post-Paleozoic mollusks, yet
      stratigraphically and geographically widespread. Drilling frequencies were very
      low in the early Paleozoic (<<1%) and went up slightly in the mid-to-late
      Paleozoic. Present-day brachiopods revealed frequencies only slightly higher. The
      persistent rarity of drilling suggests that brachiopods were the secondary
      casualties of mistaken or opportunistic attacks by the enemies of other taxa.
      Such sporadic attacks became slightly more frequent as trophic systems escalated
      and predators diversified. Some evolutionarily persistent biotic interactions may
      be incidental rather than coevolutionary or escalatory in nature.

PMID- 15961668
TI  - Nodulation signaling in legumes requires NSP2, a member of the GRAS family of
      transcriptional regulators.
AB  - Rhizobial bacteria enter a symbiotic interaction with legumes, activating diverse
      responses in roots through the lipochito oligosaccharide signaling molecule Nod
      factor. Here, we show that NSP2 from Medicago truncatula encodes a GRAS protein
      essential for Nod-factor signaling. NSP2 functions downstream of Nod-factor
      induced calcium spiking and a calcium/calmodulin-dependent protein kinase. We
      show that NSP2-GFP expressed from a constitutive promoter is localized to the
      endoplasmic reticulum/nuclear envelope and relocalizes to the nucleus after Nod
      factor elicitation. This work provides evidence that a GRAS protein transduces
      calcium signals in plants and provides a possible regulator of Nod-factor
      inducible gene expression.

PMID- 15961669
TI  - NSP1 of the GRAS protein family is essential for rhizobial Nod factor-induced
      transcription.
AB  - Rhizobial Nod factors induce in their legume hosts the expression of many genes
      and set in motion developmental processes leading to root nodule formation. Here
      we report the identification of the Medicago GRAS-type protein Nodulation
      signaling pathway 1 (NSP1), which is essential for all known Nod factor-induced
      changes in gene expression. NSP1 is constitutively expressed, and so it acts as a
      primary transcriptional regulator mediating all known Nod factor-induced
      transcriptional responses, and therefore, we named it a Nod factor response
      factor.

PMID- 15961671
TI  - Complementary process to response bias in the centromedian nucleus of the
      thalamus.
AB  - Activity in several areas of the human brain and the monkey brain increases when
      a subject anticipates events associated with a reward, implicating a role for
      bias of decision and action. However, in real life, events do not always appear
      as expected, and we must choose an undesirable action. More than half of the
      neurons in the monkey centromedian (CM) thalamus were selectively activated when
      a small-reward action was required but a large-reward option was anticipated.
      Electrical stimulation of the CM after a large-reward action request substituted
      a brisk performance with a sluggish performance. These results suggest
      involvement of the CM in a mechanism complementary to decision and action bias.

PMID- 15961670
TI  - Major dissociation between medial and lateral entorhinal input to dorsal
      hippocampus.
AB  - Hippocampal place cells are a model system of how the brain constructs cognitive
      representations and of how these representations support complex behavior,
      learning, and memory. There is, however, a lack of detailed knowledge about the
      properties of hippocampal afferents. We recorded multiple single units from the
      hippocampus and the medial and lateral entorhinal areas of behaving rats.
      Although many medial entorhinal neurons had highly specific place fields, lateral
      entorhinal neurons displayed weak spatial specificity. This finding demonstrates
      a fundamental dissociation between the information conveyed to the hippocampus by
      its major input streams, with spatial information represented by the medial and
      nonspatial information represented by the lateral entorhinal cortex.

PMID- 15961672
TI  - Selective effects of the anticancer drug Yondelis (ET-743) on cell-cycle
      promoters.
AB  - Yondelis is a potent DNA-binding anticancer drug isolated from the tunicate
      Ecteinascidia turbinata currently undergoing phase III clinical trials. We and
      others have shown selective inhibition to the transcriptional induction of
      several genes. We tested the hypothesis that Yondelis specifically targets cell
      cycle genes. Our analysis on endogenous and transfected reporter systems revealed
      complex patterns of transcriptional inhibition and, surprisingly, activation.
      Other inducible systems-the metallothionein and the CYP3A4 promoters-were little
      affected. We assayed whether interference of DNA binding of the common nuclear
      factor Y (NF-Y) activator was responsible for the observed inhibition: in vivo
      chromatin immunoprecipitation analysis in NIH3T3 and HCT116 cells indicates that
      NF-Y binding is little affected by Yondelis addition. Finally, histone
      acetylation was modestly affected only on Cdc2 and cyclin B2 but not on other
      repressed promoters. These data prove that Yondelis is not a general inhibitor of
      inducible genes, and its selective effects are exerted downstream from
      transcription factors binding and histone acetyl transferases recruitment.

PMID- 15961673
TI  - Enhanced CCAAT/enhancer-binding protein beta-liver-enriched inhibitory protein
      production by Oltipraz, which accompanies CUG repeat-binding protein-1 (CUGBP1)
      RNA-binding protein activation, leads to inhibition of preadipocyte
      differentiation.
AB  - The CCAAT/enhancer-binding protein (C/EBP) beta-isoforms liver-enriched activator
      protein (LAP) and truncated dominant-negative liver-enriched inhibitory protein
      (LIP) differentially regulate adipogenesis. We previously demonstrated that
      oltipraz (5-[2-pyrazinyl]-4-methyl-1,2-dithiol-3-thione), a cancer
      chemopreventive agent, promotes C/EBPbeta-LAP activation in hepatocytes. This
      study investigated whether oltipraz affects adipocyte differentiation and, if so,
      the molecular basis for the alterations in adipogenesis. The expression of LIP
      notably increased 6 to 48 h after oltipraz treatment of 3T3-L1 preadipocytes,
      whereas that of LAP was minimally changed. Oltipraz treatment approximately 3
      fold elevated the ratio of LIP to LAP. Immunoblot, gel-shift, and Southwestern
      analyses revealed that oltipraz enhanced the levels of nuclear LIP and LAP and
      their binding to the C/EBP-binding site. Cotransfection of predipocytes with the
      plasmid encoding LIP interfered with LAP-mediated luciferase expression,
      confirming the inhibitory role of LIP in gene expression. Likewise, LAP-mediated
      luciferase gene transactivation was inhibited by oltipraz, as was observed by
      cotransfection of a dominant-negative mutant form of C/EBP. Oltipraz enhanced
      cytoplasmic translocation and RNA binding of CUG repeat-binding protein-1
      (CUGBP1) but not calreticulin, another RNA-binding protein that interacts with
      C/EBPbeta mRNA. When 3T3-L1 preadipocytes were induced to differentiate by
      exposure to 3-isobutyl-1-methylxanthine, dexamethasone, and insulin, oltipraz
      markedly inhibited hormone-induced adipocyte differentiation. In primary cultured
      rat preadipocytes, oltipraz enhanced LIP production and inhibited adipocyte
      differentiation. In conclusion, oltipraz inhibits adipogenesis by promoting LIP
      production and activation, and the enhanced LIP production accompanies
      cytoplasmic translocation of CUGBP1 and its binding to the GC-rich region of
      C/EBPbeta mRNA. Our finding holds significance in that adipogenesis can be
      pharmacologically controlled by LIP production.

PMID- 15961674
TI  - The role of Thr139 in the human immunodeficiency virus type 1 reverse
      transcriptase sensitivity to (+)-calanolide A.
AB  - The coumarins represent a unique class of non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) that were isolated from tropical plants. (+)-Calanolide A,
      the most potent compound of this class, selects for the T139I resistance mutation
      in HIV-1 reverse transcriptase (RT). Seven RTs mutated at amino acid position 139
      (Ala, Lys, Tyr, Asp, Ile, Ser, and Gln) were constructed by site-directed
      mutagenesis. The mutant T139Q enzyme retained full catalytic activity compared
      with wild-type RT, whereas the mutant T139I, T139S, and T139A RTs retained only
      85 to 50% of the activity. Mutant T139K, T139D, and T139Y RTs had seriously
      impaired catalytic activities. The mutations in the T139I and T139D RTs were
      shown to destabilize the RT heterodimer. (+)-Calanolide A lost inhibitory
      activity (up to 20-fold) against the mutant T139Y, T139Q, T139K, and T139I
      enzymes. All of the mutant enzymes retained marked susceptibility toward the
      other NNRTIs, including nevirapine, delavirdine, efavirenz, thiocarboxanilide UC
      781, quinoxaline GW867420X, TSAO [[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D
      ribofuranosyl]-3'-spiro-5''-(4''-amino-1'',2''-oxathiole-2'',2''-dioxide)]
      derivatives, and the nucleoside inhibitor, ddGTP. The fact that the T139I RT 1)
      proved to be resistant to (+)-calanolide A, 2) represents a catalytically
      efficient enzyme, and 3) requires only a single transition point mutation (ACA-
      >ATA) in codon 139 seems to explain why mutant T139I RT virus strains, but not
      virus strains containing other amino acid changes at this position, predominantly
      emerge in cell cultures under (+)-calanolide A pressure.

PMID- 15961676
TI  - The effect of severe undernutrition and subsequent refeeding on whole-body
      metabolism and protein synthesis in human subjects.
AB  - BACKGROUND: To determine the consequences of severe undernutrition and refeeding
      on whole-body metabolism and protein synthesis. METHODS: Respiratory quotient
      (RQ), resting energy expenditure (REE), and whole-body protein synthesis (WBPS)
      were assessed in undernourished patients, with anorexia nervosa (n = 8) or with
      coexistent disease (n = 17). Results were compared with 17 healthy controls. Six
      anorexic patients and 13 disease patients consented to study after nutrition
      support. RESULTS: Mean body mass index was 12.46 +/- 0.53 kg/m2 in the anorexia
      patients and 13.81 +/- 0.40 kg/m2 in the disease patients (controls 23.71 +/-
      0.72 kg/m2; p < .001). Compared with controls, RQ was similar in anorexia
      patients (0.85 +/- 0.05 vs 0.90 +/- 0.05) but lower in the disease patients (0.76
      +/- 0.03 vs 0.90 +/- 0.05; p = .02). REE was lower in the patients (anorexia 1058
      +/- 134.0 kcal/d, disease 1189 +/- 101.4 kcal/d vs 1828 +/- 89.76 kcal/d; p <
      .001); however, expressed as kcal/kg/d, it was higher (anorexia 32.17 +/- 4.25,
      disease 31.30 +/- 2.14 vs 25.07 +/- 1.00; p < .05). WBPS was lower in the
      patients (anorexia 140.9 +/- 10.54 g/d, disease 119.8 +/- 8.57 g/d vs 305.0 +/-
      21.64 g/d; p < .001); however, when expressed as g/kg/d, the anorexia patients
      were similar to controls, whereas the disease patients were lower (3.11 +/- 0.24
      vs 4.27 +/- 0.32; p < .05). Refeeding increased RQ in the disease patients (0.84
      +/- 0.03 vs 0.76 +/- 0.03; p < .05), and normalized REE (anorexia 27.65 +/- 3.05
      kcal/kg/d, disease 28.90 +/- 1.85 kcal/kg/d). WBPS increased in the disease
      patients (173.6 +/- 16.38 g/d vs 116.5 +/- 10.15 g/d; p < .01). CONCLUSIONS:
      Undernutrition is associated with increased REE (kcal/kg/d). Reduction in RQ and
      protein synthesis (g/kg/d) was evident in those patients with coexistent disease.
      Refeeding resulted in normalization of RQ, REE (kcal/kg/d), and protein synthesis
      (g/kg/d).

PMID- 15961677
TI  - Hypoleptinemia in gastric cancer patients: relation to body fat mass, insulin,
      and growth hormone.
AB  - BACKGROUND: It remains elusive whether there are other causes besides body fat
      mass wasting contributing to decreased leptin level in cancer cachexia patients.
      This study attempts to explore possible factors influencing leptin levels in
      patients with gastric cancer. METHODS: Hormones levels (including leptin,
      insulin, growth hormone (GH), insulin-like growth factor I, glucagons, and
      cortisol), acute phase reactant, and body composition were measured in 88 gastric
      cancer patients and 24 healthy controls. All patients were divided into weight
      loss (48 patients) or nonweight-loss (40 patients) groups and cachexia (body mass
      index <18; 13 patients) or noncachexia (75 patients) groups. The detection was
      repeated 3 months after radical surgery in 16 patients. RESULTS: Compared with
      the controls, leptin levels decreased in gastric cancer patients with and without
      weight loss (p < .001 and p = .003, respectively), even when the percentage of
      fat mass was adjusted (p = .004 and 0.018, respectively). GH and insulin levels
      also changed significantly. Similar results were also found in patients with and
      without cachexia. Multivariate regression analysis showed that the percentages of
      fat mass (standardized coefficient [SC] = 0.631, p < .001), GH (SC = -0.244, p =
      .005) and insulin (SC = 0.201, p = .020) were significantly correlated with
      leptin. In the 16 patients who underwent radical surgery, leptin levels remained
      low and no significant changes in the other hormones were detected. CONCLUSIONS:
      Our results showed that low leptin levels in gastric cancer patients depended not
      only on the percentage of fat mass, but also on GH and insulin levels. Chronic
      high GH and low insulin levels may inhibit the leptin secretion.

PMID- 15961678
TI  - Preoperative oral supplementation with long-chain Omega-3 fatty acids
      beneficially alters phospholipid fatty acid patterns in liver, gut mucosa, and
      tumor tissue.
AB  - BACKGROUND: The uptake of omega-3 polyunsaturated fatty acids (PUFAs) into the
      liver, gut mucosa, and tumor tissue and plasma levels after preoperative
      administration of supplemented enteral nutrition was investigated in patients
      with malignancies of the upper gastrointestinal tract. The objective of the study
      was to evaluate the incorporation of preoperatively administrated PUFAs,
      eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) into cell
      phospholipids. METHODS: Patients undergoing major gastrointestinal surgery (n =
      40) were prospectively randomized to receive a PUFA-supplemented liquid oral diet
      5 days preoperatively or an isocaloric control diet. The planned diet intake was
      1000 mL/d providing 3.7 g of PUFA. The diet was given in addition to the usual
      hospital diet. The phospholipid fractions in plasma were analyzed on the day of
      surgery. Tissue samples of liver, gut mucosa (small intestine), and tumor were
      taken during surgery and homogenized. EPA and DHA content was analyzed using
      liquid gas chromatography. RESULTS: Both patient groups (PUFA group: n = 20;
      control group: n = 20) were similar in age, weight, and surgical procedures. As
      compared with the control group, the PUFA group had significantly increased
      levels of EPA in liver tissue (0.4 vs 1.3 weight %), gut mucosa (0.3 vs 1.0
      weight %), and tumor tissue (0.3 vs 0.8 weight %). Also, the DHA levels in the
      PUFA group were significantly higher than the control group: liver tissue (4.1 vs
      7.5 weight %), gut mucosa (2.1 vs 3.7 weight %) and tumor tissue (1.9 vs 4.2
      weight %). CONCLUSIONS: This study suggests that administration of PUFA-enriched
      diets leads to increased incorporation of EPA and DHA not only in liver and gut
      mucosa tissue, but also in tumor tissue in patients with solid gastrointestinal
      tumors. Thus, preoperative administration of oral PUFA-enriched diets could have
      an impact on the postoperative inflammatory response after major abdominal
      surgery.

PMID- 15961679
TI  - Importance of parenteral nutrition in patients undergoing hemopoietic stem cell
      transplantation procedures in the autologous system.
AB  - OBJECTIVE: The aim of this study was to assess the frequency of parenteral
      nutrition and to compare the impact of parenteral and oral feeding on the
      nutrition and clinical status of adults undergoing autologous hemopoietic stem
      cell transplantation. METHODS: The study involved 35 patients with neoplasm of
      the hemopoietic system who underwent hemopoietic cell autotransplantation at the
      Hematology Clinic (Jagiellonian University, Krakow, Poland). The patients'
      nutrition status was assessed using body mass index (BMI) values, body mass
      components, concentration of albumin, and total protein in blood serum. The
      clinical status evaluation included duration of hematologic reconstruction,
      concentration of bilirubin, enzyme activity (alanine aminotransferase and
      aspartate aminotransferase), severity of infections, and duration of
      hospitalization. RESULTS: Parenteral nutrition was required in 19 patients. Oral
      feeding was used in 16 patients. Symptoms of malnutrition on the day preceding
      the introduction of conditioning treatment were recorded only in patients
      requiring parenteral nutrition (31.6%). In the posttransplantation period, a
      statistically significant decrease in body mass was observed in both groups,
      whereas the share of fatty tissue in total body mass was significantly less in
      patients (men and women) fed parenterally. CONCLUSION: A supply of 25-30 kcal/kg
      and 1-1.5 g protein/kg/day as an element of parenteral nutrition (where 20%-30%
      of the energy requirement was covered by fats, 15%-20% by amino acids, and 50%
      55% by glucose) helped prevent the development of malnutrition and restore the
      functions of the hemopoietic system at a level comparable to that for patients
      fed naturally.

PMID- 15961680
TI  - Intestinal growth in parenterally-fed rats induced by the combined effects of
      glucagon-like peptide 2 and epidermal growth factor.
AB  - BACKGROUND: Parenteral nutrition and the absence of luminal feeding result in
      impaired intestinal growth and differentiation of enterocytes. Glucagon-like
      peptide 2 (GLP-2) and epidermal growth factor (EGF) have each been shown to have
      trophic effects on the intestine, and thus have the potential to benefit patients
      fed parenterally, such as those with intestinal failure from short bowel
      syndrome. We report studies aimed to determine whether there may be synergistic
      effects of these 2 peptides. METHODS: Rats were established on parenteral
      nutrition (PN) and infused for 6 days with GLP-2 (20 microg/d), EGF (20
      microg/d), or GLP-2 + EGF (20 microg/d of each). These groups were compared with
      untreated PN-fed and orally-fed controls. Tissue was obtained from small
      intestine and colon to determine growth, proliferation, and representative gene
      expression. RESULTS: Small intestinal weight was increased by 75%, 43%, and 116%
      in the GLP-2, EGF, and GLP-2 + EGF groups, respectively, compared with PN
      controls (all p < .001). Cell proliferation increased with GLP-2, EGF, and GLP-2
      + EGF in proximal small intestine by factors of 2.3, 1.7, and 3.4 respectively (p
      < .001). A synergistic effect on villous and crypt area was observed in the
      proximal small intestine when GLP-2 and EGF were combined (p < .05). GLP-2 had no
      effect in the colon, unlike EGF. Further studies showed GLP-2 + EGF significantly
      increased expression in distal small intestine of transcripts for the bile acid
      transport protein IBABP (p < .05) and showed a significant correlation between
      the expression of IBABP and the transcription factor HNF-4. CONCLUSIONS: Both GLP
      2 and EGF upregulate growth of the small intestine, and this is augmented when
      GLP-2 and EGF are combined. These findings may lead to improved treatment of
      patients receiving PN.

PMID- 15961681
TI  - Effect of amino acid infusion on human postoperative colon protein synthesis in
      situ.
AB  - BACKGROUND: Amino acids are an integral part of parenteral nutrition because of
      their anabolic action helping to conserve body protein after surgical stress. At
      the gastrointestinal tract, an adequate supply of amino acids may be particularly
      important because of the gut's high rate of protein turnover, cell division, and
      proliferation. However, no information is available about the effects of amino
      acids on human intestinal protein metabolism after surgery. METHODS: Studies were
      performed in postabsorptive patients 8-10 days after major abdominal surgery.
      Mass spectrometry techniques (capillary gas chromatography/combustion isotope
      ratio mass spectrometry) were used to directly determine the incorporation rate
      of 1-[13C]-leucine into colon mucosal protein. All subjects had a colostomy,
      which allowed easy access to the colon mucosa, and consecutive sampling from the
      same tissue was performed during continuous isotope infusion (0.16 micromol/kg
      min). Isotopic enrichments were determined at baseline and after a 4-hour
      infusion of amino acids or after infusion of saline (control group). RESULTS:
      Compared with baseline, infusion of amino acids reduced fractional colon protein
      synthesis significantly by -29.2 +/- 8.3%. This decrease was also significantly
      different from the corresponding (insignificant) change during saline infusion
      (+19.4 +/- 26.9%, p < .05 vs amino acid group). CONCLUSIONS: After surgery, an
      amino acid infusion acutely reduces postoperative colon protein synthesis. This
      effect possibly may be attributed to interactions of specific amino acids
      (glutamine) with an altered intestinal immune system and enterocyte activity.

PMID- 15961682
TI  - Effects of parenteral nutrition supplemented with alanyl-glutamine on nutrition
      status in rats.
AB  - BACKGROUND: Glutamine, a nonessential amino acid, has received increasing
      attention because it becomes essential during stress and catabolic conditions.
      Many investigations have shown that during severe stress, the consumption of
      glutamine exceeds glutamine synthesis, resulting in depletion of glutamine
      stores. The aim of this study was to evaluate the effects of supplementing
      parenteral diets with a glutamine-containing dipeptide, L-alanyl-L-glutamine, on
      rat nutrition status. METHODS: Male Wistar rats were used. Animals (n = 36) were
      centrally catheterized and randomly assigned to 1 of the following groups based
      on method of parenteral nutrition (PN): control group with oral nutrition and IV
      infusion of a saline solution; standard parenteral nutrition (SPN) group; or
      alanyl-glutamine-supplemented PN (ALA-GLN PN) group (20 g/L). Parenteral
      nutrition was isocaloric and isonitrogenous. Infusions were administered at a
      rate of 2.0 mL/h over 5 days. Nutrition status was assessed by body weight
      change, plasma proteins, accumulated urinary creatinine, and nitrogen balance.
      RESULTS: Accumulated urinary creatinine increased significantly after day 4 in
      the ALA-GLN PN group, compared with the SPN group and the controls. Body weight
      change significantly differed on day 5 between the ALA-GLN PN and SPN groups.
      After 3 days, nitrogen balance was significantly lower and nitrogen retention
      higher in the ALA-GLN PN group when compared with the SPN group. Albumin and
      transferrin concentrations decreased significantly in the SPN group, but did not
      differ from the controls in the ALA-GLN PN group. CONCLUSIONS: Weight, plasma
      proteins, urinary accumulated creatinine, and nitrogen retention showed a better
      evolution in the group supplemented with the glutamine dipeptide when compared
      with the SPN group. Our results suggest a more suitable nutrition support in
      animals receiving L-alanyl-L-glutamine.

PMID- 15961683
TI  - Economic analysis of home vs hospital-based parenteral nutrition in Ontario,
      Canada.
AB  - BACKGROUND: Advances in technology and infrastructure have facilitated transfer
      of complex services from acute care hospitals to the home. This increases the
      burden on community resources but may provide net savings to the health care
      system. We undertook a retrospective cohort study of patients transferred from
      hospital to home while receiving home parenteral nutrition (PN) to assess their
      costs of care. METHODS: A detailed review of medical records was undertaken for
      all patients managed by the Hamilton Health Sciences Home PN Program between 1996
      and 2001 whose PN was initiated in hospital. Mean per diem direct medical costs
      were estimated from the perspective of the provincial Ministry of Health for 3
      periods: the last 2 weeks before discharge and the first month after discharge.
      Costs were compared among time intervals and among patients subgroups defined by
      age and underlying disease. RESULTS: Twenty-nine eligible subjects were
      identified. Common indications for PN included malignancy (n = 12), inflammatory
      bowel disease (n = 6), and intestinal ischemia (n = 4). Mean per diem costs in
      the last week of hospitalization were higher than those in the first month after
      discharge (dollars 567 vs dollars 405, p < .0001). Acute care resources accounted
      for <10% of the overall costs on home PN. The estimated monthly savings per
      patient maintained on home PN were dollars 4860 (95% confidence interval dollars
      2700-dollars 7000). Savings were even greater among patients with underlying
      malignancy and advanced age. CONCLUSIONS: Home PN is cost saving when compared
      with hospital-based PN. Neither age nor underlying malignancy should pose a
      barrier to receipt of home PN.

PMID- 15961684
TI  - Celiac disease unmasked after pancreaticoduodenectomy.

PMID- 15961685
TI  - Rhoads Lecture: a 45-year obsession and passionate pursuit of optimal nutrition
      support: puppies, pediatrics, surgery, geriatrics, home TPN, A.S.P.E.N., et
      cetera.

PMID- 15961686
TI  - Severe obesity: a growing health concern A.S.P.E.N. should not ignore.
AB  - The definition of malnutrition in the published standards of the American Society
      of Parenteral and Enteral Nutrition (A.S.P.E.N.) is any derangement in the normal
      nutrition status and includes overnutrition, commonly referred to as obesity. The
      incidence of obesity is increasing and reaching epidemic proportions in the
      United States and even worldwide. This has significant financial impact as our
      society spends billions of dollars on fad diets, commercial weight-loss programs,
      nutrition and dietary supplements, prescription and over-the-counter medications,
      and health clubs. Another approximately dollars 100 billion are spent to treat
      the medical consequences of obesity. Currently, for those patients with
      intractable morbid obesity, defined as having a body mass index >40 kg/m2,
      surgery offers the only option for achieving meaningful and sustainable weight
      loss. The resultant weight loss dramatically improves health and decreases the
      cost of health care for these patients. Years of refinement in technology and the
      introduction of safer and less invasive procedures have dramatically reduced the
      short-term morbidities and long-term metabolic consequences of these procedures.
      This address will review the field of weight loss (bariatric) surgery and will
      offer a compelling request for A.S.P.E.N. to include obesity in its fabric.

PMID- 15961687
TI  - Preoperative fasting: an outdated concept?
AB  - Recent studies have shown that fasting during the preoperative period for
      elective surgery induces a metabolic state that seems unfavorable for patients.
      Results from animal studies indicate that rapid depletion of liver glycogen
      before surgery leads to mobilization of muscle glycogen after surgery, in turn
      leading to reduced muscle strength. Depletion of liver glycogen also influences
      the function of the mononuclear phagocytic system (MPS), which is located
      predominantly in the liver. The MPS is essential in restricting endotoxin, which
      may translocate from the gut. In addition, surgery per se puts a substantial
      physical strain on the patient, and fasting may adversely affect the metabolic
      response to surgery. This paper presents experimental and clinical data that,
      when combined together, prove that fasting before surgery has adverse
      consequences for the patient.

PMID- 15961688
TI  - Noninvasive verification of nasogastric tube placement using a magnet-tracking
      system: a pilot study in healthy subjects.
AB  - BACKGROUND: Fluoroscopic verification of nasogastric (NG) feeding tube placement
      is inconvenient and involves radiation exposure. We tested whether the position
      of an NG tube can be assessed reliably by a recently introduced magnet-tracking
      system. METHODS: A small permanent magnet was attached at the end of an NG tube
      and its position was monitored using an external sensor array connected to a
      computer. NG tube trajectory, spontaneous movements of the magnet, and its
      position relative to the lower esophageal sphincter (LES) and xiphisternum were
      assessed in 22 healthy subjects and compared with esophageal manometry. In 12
      subjects, localization of the magnet was also compared with fluoroscopy. RESULTS:
      Magnet-tracking displayed NG tube tip movement reproducibly as it moved
      vertically in the esophagus and then laterally into the stomach. Compared with
      manometry, the accuracy and sensitivity of magnet tracking for localization of
      the NG tube tip, above or below the diaphragm, were 100%. Compared with
      fluoroscopy, the accuracy of NG tube localization by magnet tracking was 100%.
      With the magnet in the stomach, but not in the esophagus or LES, low amplitude
      displacements at a frequency of 3 per minute, consistent with gastric slow wave
      activity, were observed. CONCLUSIONS: Magnet tracking allows accurate, real-time,
      3-dimensional localization of an NG tube with respect to anatomic landmarks.
      Recorded motor patterns are indicative of the position of the NG tube. Magnet
      tracking may be a useful tool for bedside placement of nasogastric and enteral
      feeding tubes.

PMID- 15961689
TI  - Health care for all.

PMID- 15961690
TI  - Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma
      pathogenesis?
AB  - The potential role of atypical bacterial infection in the pathogenesis of asthma
      is a subject of continuing debate. There is an increasing body of literature
      concerning the association between the atypical bacteria Chlamydophila pneumoniae
      and Mycoplasma pneumoniae and asthma pathogenesis; however, many studies
      investigating such a link have been uncontrolled and have provided conflicting
      evidence, in part due to the difficulty in accurately diagnosing infection with
      these atypical pathogens. This article reviews the evidence for an association
      between atypical bacterial respiratory pathogens and the pathogenesis of asthma,
      and discusses the biological mechanisms that could account for such a link. The
      possible role of antibacterial therapy in the management of asthma and the need
      for well-designed studies to investigate this is also discussed.

PMID- 15961691
TI  - Roflumilast fully prevents emphysema in mice chronically exposed to cigarette
      smoke.
AB  - RATIONALE: There is a need for new agents capable of suppressing the inflammatory
      response in chronic obstructive pulmonary disease. OBJECTIVES: This study
      evaluated the effects of roflumilast, a phosphodiesterase 4 (PDE4) inhibitor on
      acute lung inflammation and chronic lung changes in models of cigarette exposure
      in mice. METHODS: Roflumilast was given orally either at 1 mg/kg (R1) or at 5
      mg/kg (R5). In the acute model (five cigarettes for 20 minutes), bronchoalveolar
      lavage fluid (BALF) changes were investigated at 4 and 24 hours. In the chronic
      model (three cigarettes/day for 7 months), morphometric and biochemical
      parameters were assessed at 7 months. MEASUREMENTS AND MAIN RESULTS: Acute
      exposure caused a fivefold increase in BALF neutrophils. Both doses of
      roflumilast partially prevented (by 30%) this increase. In addition, after smoke
      exposure, R1 increased BALF interleukin-10 by 79% and R5 by 129%. Chronic smoke
      exposure caused a 1.8-fold increase in lung macrophage density, emphysema, an
      increase of the mean linear intercept (+21%), a decrease of the internal surface
      area (-13%), and a drop (-13%) in lung desmosine content. R1 did not have any
      effect, whereas R5 prevented the increase in lung macrophage density by 70% and
      fully prevented the other changes. In addition, in the smoke-exposure group, 63%
      of the mice showed goblet cell metaplasia, and neither of the doses of
      roflumilast had any effect. CONCLUSIONS: This study shows for the first time that
      a PDE4 inhibitor partially ameliorates lung inflammation and fully prevents
      parenchymal destruction induced by cigarette smoke.

PMID- 15961692
TI  - Treatment of experimental asthma by decoy-mediated local inhibition of activator
      protein-1.
AB  - RATIONALE: Asthma is associated with increased expression of a typical array of
      genes involved in immune and inflammatory responses, including those encoding the
      prototypic Th2 cytokines interleukin (IL) 4, IL-5, and IL-13. Most of these genes
      contain binding sites for activator protein-1 (AP-1) within their promoter and
      are therefore believed to depend on AP-1 for their expression, suggesting that
      this transcription factor could be of particular importance in asthma
      pathophysiology. OBJECTIVE: To clarify the role of AP-1 in the effector phase of
      pulmonary allergy. METHODS: Ovalbumin (OVA)-sensitized mice were intratracheally
      given decoy oligodeoxyribonucleotides (ODNs) specifically directed to AP-1 or
      scrambled control ODNs before challenge with aerosolized OVA. Twenty-four hours
      after the last OVA challenge, airway hyperresponsiveness was measured and
      allergic airway inflammation was evaluated quantitatively. AP-1 decoys were
      localized using flow cytometry and immunohistochemistry. AP-1 activity in the
      lung was assessed using electrophoretic mobility shift assay. MEASUREMENTS AND
      MAIN RESULTS: Intratracheally delivered AP-1 decoys efficiently targeted airway
      immune cells, thus precluding AP-1 activation on OVA challenge. Decoy-mediated
      local inhibition of AP-1 resulted in significant attenuation of all the
      pathophysiologic features of experimental asthma-namely, eosinophilic airway
      inflammation, airway hyperresponsiveness, mucous cell hyperplasia, production of
      allergen-specific immunoglobulins, and synthesis of IL-4, IL-5, and IL-13.
      Scrambled control ODNs had no detectable effects. CONCLUSIONS: Our results reveal
      a key role for AP-1 in the effector phase of pulmonary allergy and indicate that
      specific AP-1 inhibition in the airways may have therapeutic value in the control
      of established asthma.

PMID- 15961694
TI  - One hundred years of lung cancer.
AB  - A hundred years ago, lung cancer was a reportable disease, and it is now the
      commonest cause of death from cancer in both men and women in the developed
      world, and before long, will reach that level in the developing world as well.
      The disease has no particular symptoms or signs for its detection at an early
      stage. Most patients therefore present with advanced stage IIIB or IV disease.
      Screening tests began in the 1950s with annual chest x-ray films and sputum
      cytology but they resulted in no improvement in overall mortality compared with
      control subjects. The same question is now being asked of spiral low-dose
      computed tomographic scanning. There have been big refinements in the staging
      classification of lung cancer and advances in stage identification using
      minimally invasive technology. Postsurgical mortality has declined from the early
      days of the 1950s but 5-year cure rates have only barely improved. The addition
      of chemotherapy to radical radiotherapy, together with novel radiotherapy
      techniques, is gradually improving the outcome for locally advanced, inoperable
      non-small cell lung cancer. Chemotherapy offers modest survival improvement for
      patients with non-small cell lung cancer, the modern agents being better
      tolerated resulting in an improved quality of life. The management of small cell
      lung cancer, which appeared so promising at the beginning of the 1970s, has hit a
      plateau with very little advance in outcome over the last 15 years. The most
      important and cost-effective management for lung cancer is smoking cessation, but
      for those with the disease, novel agents and treatment approaches are urgently
      needed.

PMID- 15961693
TI  - Diminished lipoxin biosynthesis in severe asthma.
AB  - RATIONALE AND OBJECTIVES: Severe asthma is characterized by increased airway
      inflammation that persists despite therapy with corticosteroids. It is not,
      however, merely an exaggeration of the eosinophilic inflammation that
      characterizes mild to moderate asthma; rather, severe asthma presents unique
      features. Although arachidonic acid metabolism is well appreciated to regulate
      airway inflammation and reactivity, alterations in the biosynthetic capacity for
      both pro- and antiinflammatory eicosanoids in severe asthma have not been
      determined. METHODS: Patients with severe asthma were identified according to
      National Heart, Lung, and Blood Institute Severe Asthma Research Program
      criteria. Samples of whole blood from individuals with severe or moderate asthma
      were assayed for biosynthesis of lipoxygenase-derived eicosanoids. MEASUREMENTS
      AND MAIN RESULTS: The counterregulatory mediator lipoxin A4 was detectable in low
      picogram amounts, using a novel fluorescence-based detection system. In activated
      whole blood, mean lipoxin A4 levels were decreased in severe compared with
      moderate asthma (0.4 [SD 0.4] ng/ml vs. 1.8 [SD 0.8] ng/ml, p=0.001). In sharp
      contrast, mean levels of prophlogistic cysteinyl leukotrienes were increased in
      samples from severe compared with moderate asthma (112.5 [SD 53.7] pg/ml vs. 64.4
      [SD 24.8] pg/ml, p=0.03). Basal circulating levels of lipoxin A4 were also
      decreased in severe relative to moderate asthma. The marked imbalance in
      lipoxygenase-derived eicosanoid biosynthesis correlated with the degree of
      airflow obstruction. CONCLUSIONS: Mechanisms underlying airway responses in
      severe asthma include underproduction of lipoxins. This is the first report of a
      defect in lipoxin biosynthesis in severe asthma, and suggests an alternative
      therapeutic strategy that emphasizes natural counterregulatory pathways in the
      airways.

PMID- 15961695
TI  - Quality of life, physical disability, and respiratory impairment in Duchenne
      muscular dystrophy.
AB  - RATIONALE: Duchenne muscular dystrophy (DMD) leads to progressive, generalized
      paresis, and to respiratory failure in the second decade of life. The assumption
      that severe physical disability precludes an acceptable quality of life is
      common, but has not been specifically evaluated in DMD. OBJECTIVES: The purpose
      of this study was to investigate the quality of life in relation to physical
      disability, pulmonary function, and the need for assisted ventilation in DMD.
      METHODS: In 35 patients with DMD, aged 8-33 yr, we assessed physical disability
      by a score ranging from 9 (no disability) to 80 (complete dependence on care and
      technical aids), pulmonary function, and health-related quality of life by Short
      Form 36 of the medical outcome questionnaire. MEASUREMENTS AND MAIN RESULTS: All
      patients required a wheelchair and help for dressing and eating. Fourteen
      patients were on long-term noninvasive positive-pressure ventilation. In
      ventilated patients, mean +/- SD FVC was 12 +/- 10 % predicted, and the physical
      disability score was 65 +/- 7. Corresponding values in spontaneously breathing
      patients were 48 +/- 25 % predicted, and 51 +/- 7, respectively (p < 0.05 for
      both comparisons between groups). Short-Form 36 physical function scores were
      massively reduced in both groups (1 +/- 2, and 0 +/- 0, respectively), but
      vitality, role-emotional, social function, and mental health scores were nearly
      normal (67-98), and did not differ between groups. CONCLUSIONS: Quality of life
      in DMD is not correlated with physical impairment nor the need for noninvasive
      positive-pressure ventilation. The surprisingly high quality of life experienced
      by these severely disabled patients should be taken into consideration when
      therapeutic decisions are made.

PMID- 15961696
TI  - Routine hospital use of a new commercial whole blood interferon-gamma assay for
      the diagnosis of tuberculosis infection.
AB  - RATIONALE: Interferon (IFN)-gamma blood tests may improve the current level of
      diagnostic accuracy for tuberculosis infection. The QuantiFERON-TB Gold (QFT
      Gold) has been used in selected populations and shows higher specificity than the
      tuberculin skin test (TST). OBJECTIVE: To evaluate the QFT-Gold test in
      unselected patients and assess the level of agreement with the TST. METHODS: The
      test has been routinely performed on whole blood samples in our microbiology
      laboratory for 8 months. Demographic, clinical, and microbiological data have
      been collected and correlated to the QFT-Gold results. MEASUREMENTS AND MAIN
      RESULTS: Of 318 patients tested, 68 (21.4%) gave an indeterminate (low positive
      mitogen control) QFT-Gold result. Indeterminate results were significantly
      overrepresented in patients with a negative TST (28.9% vs. 6.6% in TST-positive
      patients; p < 0.0001, chi2 test) and were more frequent in patients receiving
      immunosuppressive therapies than in those who were not receiving such treatments
      (odds ratio, 3.35; 95% confidence interval, 1.84-6.08; p < 0.0001). After
      excluding indeterminate results, the concordance between QFT-Gold and TST was
      significantly lower in Bacille Calmette-Guerin-vaccinated individuals (41.5%)
      than in nonvaccinated individuals (80.3%) (p < 0.0001). In 11 patients with
      active tuberculosis (5 culture-confirmed), QFT-Gold provided more positive
      results than the TST (66.7% vs. 33.3%; p = 0.165). CONCLUSIONS: The QFT-Gold test
      is feasible in routine hospital use for the diagnosis of tuberculosis infection.
      As with the TST, immunosuppression may negatively affect the test's performance,
      with a significant rate of indeterminate results in the most vulnerable
      population.

PMID- 15961698
TI  - Inhaled corticosteroids and the beneficial effect of deep inspiration in asthma.
AB  - Deep inspiration-induced bronchoprotection and bronchodilation are impaired in
      asthma. We evaluated the effect of inhaled glucocorticosteroids on these
      phenomena. Two groups of subjects with asthma, 9 with moderate/severe
      hyperresponsiveness to methacholine, and 12 with mild/borderline
      hyperresponsiveness to methacholine, received inhaled fluticasone (880 microg
      daily) for 12 weeks. Serial bronchoprovocations were performed at Weeks 0, 6, and
      12. The impact of deep inspirations on the airway response to methacholine was
      evaluated on the basis of inspiratory vital capacity and FEV(1). Fluticasone
      produced a wide spectrum of changes in the beneficial effects of deep
      inspiration, but the mean changes were not significant. The magnitude of the
      steroid-induced changes in bronchoprotection by deep inspiration correlated with
      baseline log PC(20) (the provocative concentration of methacholine causing a 20%
      fall in FEV(1); higher log PC(20) predicted improvement of the deep inspiration
      effect). The steroid-induced changes led to the emergence of strong positive
      correlations between the effects of deep inspiration and the methacholine log
      PC(20) that did not exist at baseline. We conclude that deep inspiration-induced
      bronchoprotection can be restored by inhaled glucocorticosteroids only in
      individuals with mild hyperresponsiveness. After steroid treatment, the
      beneficial effects of deep inspiration become significant determinants of the
      magnitude of airway hyperresponsiveness.

PMID- 15961697
TI  - Asthma severity and exposure to occupational asthmogens.
AB  - RATIONALE: Severe asthma is a public health problem with limited information
      regarding preventable causes. Although occupational exposures have been
      implicated as important risk factors for asthma and asthma exacerbations,
      associations between occupational exposures and asthma severity have not been
      reported. OBJECTIVE: To examine associations between occupational exposures and
      asthma severity. METHODS: The Epidemiological Study on the Genetics and
      Environment of Asthma combines a case-control study with a family study of
      relatives of patients with asthma. Adult patients (n = 148) were recruited in
      chest clinics and control subjects without asthma (n = 228) were population
      based. Occupational exposures to nonasthmogenic irritants and asthmogens
      (classified as "any asthmogen" including three broad groups: high-molecular
      weight agents, low-molecular-weight agents, and mixed environments) were assessed
      by an asthma-specific job exposure matrix. Asthma severity was defined from an 8
      grade clinical score (frequency of attacks, persistent symptoms, and
      hospitalization). Patients with severe (score >or= 2) and mild asthma were
      compared with control subjects using nominal logistic regression. MAIN RESULTS:
      Significant associations were observed between severe adult-onset asthma and
      exposure to any occupational asthmogen (odds ratio [OR], 4.0; 95% confidence
      interval [CI], 2.0-8.1), high-molecular-weight agents (OR, 3.7; CI, 1.3-11.1),
      low-molecular-weight agents (OR, 4.4; CI, 1.9-10.1), including industrial
      cleaning agents (OR, 7.2; CI, 1.3-39.9), and mixed environments (OR, 7.5; CI, 2.4
      23.5). No significant associations were found between nonasthmogenic irritants
      and asthma severity, nor between asthmogens and childhood-onset asthma or mild
      adult-onset asthma. CONCLUSIONS: Our results suggested a strong deleterious role
      of occupational asthmogens in severe asthma. Clinicians should consider
      occupational exposures in patients with moderate to severe asthma.

PMID- 15961699
TI  - Effects of different ventilator settings on sleep and inspiratory effort in
      patients with neuromuscular disease.
AB  - Patients with neuromuscular disease (NMD) who require long-term ventilation
      normally have the ventilation set using empirical daytime parameters. We
      evaluated arterial blood gases (ABG), breathing pattern, respiratory muscle
      function, and sleep architecture during ventilation with two noninvasive Pressure
      Support Ventilation (nPSV) settings in nine patients with NMD. The two settings
      were randomly applied: the usual (US), with the nPSV setting titrated on simple
      clinical parameters, and the physiological (PHYS), tailored to the patient's
      respiratory effort. During wakefulness, nPSV significantly improved ABG and
      minute ventilation and reduced the diaphragmatic pressure-time product
      (PTPdi/breath), independently of the type of setting (PTPdi/breath spontaneous
      breathing 5.7 +/- 2.4, US 3.2 +/- 2, PHYS 3.6 +/- 1.6 cm H2O . seconds(-1), p <
      0.001). However, during sleep, PHY nPSV resulted in a significant improvement of
      gas exchange, sleep efficiency (71.7% +/- 14 US vs. 80.6% +/- 8.3 PHYS, p < 0.01)
      and % of REM sleep (9.1% +/- 7 US vs. 17.3% +/- 5.4 PHYS, p < 0.01). This
      improvement was significantly correlated with the reduction in ineffective
      efforts. In NMD, nPSV is effective in improving daytime ABG and in unloading
      inspiratory muscles independently of whether it is set on the basis of the
      patient's comfort or the patient's respiratory mechanics. However, PHYS was
      associated with better sleep architecture and nighttime gas exchange.

PMID- 15961700
TI  - An oral apoJ peptide renders HDL antiinflammatory in mice and monkeys and
      dramatically reduces atherosclerosis in apolipoprotein E-null mice.
AB  - OBJECTIVE: To determine the properties of a peptide synthesized from D-amino
      acids corresponding to residues 113 to 122 in apolipoprotein (apo) J. METHODS AND
      RESULTS: In contrast to D-4F, D- [113-122]apoJ showed minimal self-association
      and helicity in the absence of lipids. D-4F increased the concentration of apoA-I
      with pre-beta mobility in apoE-null mice whereas D- [113-122]apoJ did not. After
      an oral dose D- [113-122]apoJ more slowly associated with lipoproteins and was
      cleared from plasma much more slowly than D-4F. D- [113-122]apoJ significantly
      improved the ability of plasma to promote cholesterol efflux and improved high
      density lipoprotein (HDL) inflammatory properties for up to 48 hours after a
      single oral dose in apoE-null mice, whereas scrambled D- [113-122]apoJ did not.
      Oral administration of 125 microg/mouse/d of D- [113-122]apoJ reduced
      atherosclerosis in apoE-null mice (70.2% reduction in aortic root sinus lesion
      area, P=4.3 x 10(-13); 70.5% reduction by en face analysis, P=1.5 x 10(-6)). In
      monkeys, oral D- [113-122]apoJ rapidly reduced lipoprotein lipid hydroperoxides
      (LOOH) and improved HDL inflammatory properties. Adding 250 ng/mL of D-[113
      122]apoJ (but not scrambled D- [113-122]apoJ) to plasma in vitro reduced LOOH and
      increased paraoxonase activity. CONCLUSIONS: Oral D- [113-122]apoJ significantly
      improves HDL inflammatory properties in mice and monkeys and inhibits lesion
      formation in apoE-null mice.

PMID- 15961701
TI  - Critical role of Mst1 in vascular remodeling after injury.
AB  - OBJECTIVE: Apoptosis of vascular smooth muscle cells (VSMCs) is observed in
      chronic vascular lesions such as atherosclerotic plaques and is believed to
      contribute to the vascular remodeling process. Mst1 is a ubiquitously expressed
      serine/threonine kinase known to be activated in response to a wide variety of
      nonphysiological apoptotic stimuli. However, little is known of the physiological
      function of Mst1, and its role in VSMCs has never been examined. METHODS AND
      RESULTS: Treatment of VSMCs with staurosporine induced apoptosis and cleavage of
      Mst1, which is a marker of its activation, as well as activation of caspase 3.
      Adenovirus-mediated overexpression of wild-type Mst1 (AdMst1) in VSMCs increased
      apoptotic cells with activation of caspase 3. Mst1 was induced and activated in
      the balloon-injured rat carotid artery. Infection with AdMst1 in balloon-injured
      rat carotid artery suppressed neointimal formation compared with infection with
      AdLacZ. Infection with AdMst1 significantly increased the apoptotic cell number
      in the neointima compared with infection with AdLacZ without affecting BrdU
      incorporation. CONCLUSIONS: Our results suggest that Mst1 plays an important role
      in the induction of apoptosis of VSMCs, mediating the vascular remodeling
      process, and may be a potential therapeutic target for vascular proliferative
      diseases.

PMID- 15961702
TI  - Vascular endothelium has a local anti-adenovirus vector system and glucocorticoid
      optimizes its gene transduction.
AB  - OBJECTIVE: Although adenovirus is a powerful tool for vascular research and
      therapy, endothelial impairment after infection has been reported. We
      investigated the mechanisms of this impairment and the effect of dexamethasone
      (DEX) on gene transfer into the vascular endothelial cells. METHODS AND RESULTS:
      Beta-galactosidase gene encoding adenovirus vector (beta-gal-Ad) (7.5 x 10(8)
      plaque-forming units/mL) transduced beta-gal into the rabbit organ-cultured
      pulmonary endothelium, followed by an apoptosis and an impairment of endothelium
      dependent relaxation (EDR). Endothelial cell infected by beta-gal-Ad expressed
      proinflammatory genes mRNAs and suppressed endothelial nitric oxide synthase
      (eNOS) mRNA. Treatment with DEX dramatically increased beta-gal protein
      expression in the endothelium, attenuated beta-gal-Ad-induced apoptosis, and
      prevented the impairment of EDR. DEX also suppressed the mRNAs expressions of
      proinflammatory genes and recovered eNOS mRNA expression in organ-cultured
      vascular endothelium. In addition, we confirmed the DEX's beneficial effects in
      an endothelial cell line (in vitro) and rat femoral artery (in vivo) experiments.
      CONCLUSIONS: These results suggest that adenovirus vector induces host-immune
      responses and apoptosis in vascular endothelial cells. DEX is found to be a
      useful and potent tool to prevent the Ad-induced impairments of the endothelium
      and to optimize gene expression efficiency by adenovirus vector at the protein
      translation level in both in vitro and in vivo experiments.

PMID- 15961703
TI  - Iron stores and vascular function in voluntary blood donors.
AB  - BACKGROUND: Iron is a pro-oxidant cofactor that may be linked to atherosclerosis
      progression. Reduction of body iron stores secondary to blood donation has been
      hypothesized to reduce coronary risk, but retrospective studies have yielded
      inconsistent findings. We sought to assess the effects of blood donation
      frequency on body iron stores and physiological and biochemical biomarkers of
      vascular function associated with atherosclerosis progression. METHODS AND
      RESULTS: Forty high-frequency voluntary blood donors (> or =8 donations in past 2
      years) and 42 low-frequency blood donors (1 to 2 donations in past 2 years) aged
      50 to 75 years were randomly selected from American Red Cross of Connecticut
      blood donor records. Flow-mediated dilation in the brachial artery, serum markers
      of iron stores, vascular inflammation and oxidative stress, and cardiac risk
      factors were assessed in all subjects. Serum ferritin was significantly decreased
      in high-frequency blood donors when compared with low-frequency blood donors
      (median values 17 versus 52 ng/mL; P<0.001), but hematocrit did not differ
      between groups. Flow-mediated dilation in the brachial artery was significantly
      greater in high-frequency donors when compared with low-frequency donors in
      univariate analysis (5.5+/-2.6% versus 3.8+/-1.6%; P=0.0003) and in multivariate
      analysis adjusting for cardiac risk factors and other potential confounders.
      Serum biomarkers of vascular inflammation did not differ between groups but 3
      nitrotyrosine, a marker of oxidative stress, was decreased in high-frequency
      donors when compared with low-frequency donors. CONCLUSIONS: High-frequency blood
      donors had evidence of decreased body iron stores, decreased oxidative stress,
      and enhanced vascular function when compared with low-frequency donors. These
      findings support a potential link between blood donation and reduced
      cardiovascular risk that warrants further investigation in prospective outcome
      studies.

PMID- 15961704
TI  - Processes involved in the site-specific effect of probucol on atherosclerosis in
      apolipoprotein E gene knockout mice.
AB  - OBJECTIVE: To elucidate processes by which the antioxidant probucol increases
      lesion size at the aortic sinus and decreases atherosclerosis at more distal
      sites in apolipoprotein E-deficient (apoE(-/-)) mice. METHODS AND RESULTS: Male
      apoE(-/-) mice were fed high-fat chow with 1% (w/w) probucol or without
      (controls) for 6 months, before aortic sinus, arch, and descending aorta were
      analyzed separately for lesion size and composition. Compared with control,
      probucol significantly increased lesion size by 33% at the sinus, but it
      inhibited atherosclerosis at the descending aorta by 94%. Sites where
      atherosclerosis was inhibited contained substantially fewer macrophages, less
      lipids (cholesterol and cholesteryl esters), and endogenous antioxidant (alpha
      tocopherol), but not oxidized lipids, and the extent to which probucol metabolism
      occurred was increased. Compared with control, aortic sinus lesions of probucol
      mice contained a substantially increased content of extracellular matrix, but
      decreased total cell and macrophage density, comparable levels of lipids and
      alpha-tocopherol, and decreased concentrations of oxidized lipids (cholesteryl
      ester hydroperoxides, F2-isoprostanes, and 7-ketocholesterol). CONCLUSIONS:
      Probucol affects atherosclerosis in apoE(-/-) mice independent of the
      accumulation of arterial lipid oxidation products, thereby dissociating the 2
      processes. Rather, probucol exerts antiinflammatory activity by decreasing
      accumulation of macrophages in lesions, and it promotes a more stable lesion
      composition at the aortic sinus.

PMID- 15961705
TI  - Genes of cholesterol metabolism in human atheroma: overexpression of perilipin
      and genes promoting cholesterol storage and repression of ABCA1 expression.
AB  - OBJECTIVE: Accumulation of cholesterol in foam cells of atheroma plaques depends
      on the balance between uptake and efflux of cholesterol. It may also depend on
      proteins surrounding lipid droplets, adipophilin, and perilipins. They favor
      triglyceride storage in adipocytes and could play a similar role for cholesterol
      in atheroma. METHODS AND RESULTS: We measured in human atheroma and nearby
      macroscopically intact tissue (MIT) the expression of perilipin, adipophilin, and
      regulatory factors of cholesterol metabolism. We identified perilipin A in human
      arterial wall. Its expression was largely increased in atheroma compared with
      MIT, and perilipin was present in macrophages and vascular smooth muscle cells.
      Adipophilin, ACAT1, and CD36 were also overexpressed in atheroma. mRNA levels of
      low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A
      reductase, and SREBP-2 were unchanged. With respect to efflux of cholesterol, the
      mRNA levels of NCEH and ABCA-1 were unchanged, whereas CLA-1 mRNA was slightly
      higher in atheroma. Importantly, immunoblotting of ABCA-1 showed a dramatic
      decrease of ABCA1 protein, the key molecule of cholesterol efflux, in atheroma
      compared with MIT. CONCLUSIONS: We show the presence and induction of perilipin
      in atheroma. This overexpression and the coordinated modifications of expression
      of key regulatory factors for cholesterol metabolism could favor cholesterol
      accumulation.

PMID- 15961706
TI  - Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid
      (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular
      calcification.
AB  - OBJECTIVE: Matrix gamma-carboxyglutamic acid (Gla) protein (MGP), a vitamin K
      dependent protein, is a potent in vivo inhibitor of arterial calcification. We
      hypothesized that low endogenous production of MGP and impaired carboxylation of
      MGP may contribute to the development or the progression of vascular disease.
      METHODS AND RESULTS: Novel conformation-specific antibodies against MGP were used
      for immunohistochemistry of healthy and sclerotic arteries. In healthy arteries,
      MGP was mainly displayed around the elastin fibers in the tunica media. The
      staining colocalized with that for carboxylated MGP, whereas undercarboxylated
      MGP (ucMGP) was not detected. In atherosclerotic arteries, ucMGP was found in the
      intima, where it was associated with vesicular structures. In Monckeberg's
      sclerosis of the media, ucMGP was localized around all areas of calcification.
      The results indicate that ucMGP is strongly associated with vascular
      calcification of different etiologies. In a separate study, serum MGP
      concentrations in a cohort of 172 subjects who had undergone percutaneous
      coronary intervention were significantly reduced compared with an apparently
      healthy population. CONCLUSIONS: These data show that impaired carboxylation of
      MGP is associated with intimal and medial vascular calcification and suggest the
      essentiality of the vitamin K modification to the function of MGP as an inhibitor
      of ectopic calcification.

PMID- 15961709
TI  - Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results
      of the MERCI trial.
AB  - BACKGROUND AND PURPOSE: The only Food and Drug Administration (FDA)-approved
      treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given
      intravenously within 3 hours of symptom onset. An alternative strategy for
      opening intracranial vessels during stroke is mechanical embolectomy, especially
      for patients ineligible for intravenous tPA. METHODS: We investigated the safety
      and efficacy of a novel embolectomy device (Merci Retriever) to open occluded
      intracranial large vessels within 8 hours of the onset of stroke symptoms in a
      prospective, nonrandomized, multicenter trial. All patients were ineligible for
      intravenous tPA. Primary outcomes were recanalization and safety, and secondary
      outcomes were neurological outcome at 90 days in recanalized versus
      nonrecanalized patients. RESULTS: Recanalization was achieved in 46% (69/151) of
      patients on intention to treat analysis, and in 48% (68/141) of patients in whom
      the device was deployed. This rate is significantly higher than that expected
      using an historical control of 18% (P<0.0001). Clinically significant procedural
      complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial
      hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes
      (modified Rankin score < or =2) were more frequent at 90 days in patients with
      successful recanalization compared with patients with unsuccessful recanalization
      (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and
      mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01).
      CONCLUSIONS: A novel endovascular embolectomy device can significantly restore
      vascular patency during acute ischemic stroke within 8 hours of stroke symptom
      onset and provides an alternative intervention for patients who are otherwise
      ineligible for thrombolytics.

PMID- 15961710
TI  - Racial disparities in stroke risk factors: the impact of socioeconomic status.
AB  - BACKGROUND AND PURPOSE: In the US, blacks have a higher incidence of stroke and
      more severe strokes than whites. Our objective was to determine if differences in
      income, education, and insurance, as well as differences in the prevalence of
      stroke risk factors, accounted for the association between ethnicity and stroke.
      METHODS: We used data from the Third National Health and Nutrition Survey (NHANES
      III), a cross-sectional sample of the noninstitutionalized US population (1988
      1994), and included blacks and whites aged 40 years or older with a self-reported
      stroke history. Income was assessed using a ratio of income to US Census Bureau
      annual poverty threshold. RESULTS: Among 11 163 participants, 2752 (25%) were
      black and 619 (6%) had a stroke history (blacks: 160/2752 [6%]; whites: 459/8411
      [6%]; P=0.48). Blacks had a higher prevalence of 5 risk factors independently
      associated with stroke: hypertension, treated diabetes, claudication, higher C
      reactive protein, and inactivity; whites had a higher prevalence of 3 risk
      factors: older age, myocardial infarction, and lower high-density lipoprotein
      cholesterol. Ethnicity was independently associated with stroke after adjusting
      for the 8 risk factors (adjusted odds ratio, 1.32; 95% CI, 1.04 to 1.67).
      Ethnicity was not independently associated with stroke after adjustment for
      income and income was independently associated with stroke (adjusted odds ratios
      for: ethnicity, 1.15; 95% CI, 0.88 to 1.49; income, 0.89; 95% CI, 0.82 to 0.95).
      Adjustment for neither education nor insurance altered the ethnicity-stroke
      association. CONCLUSIONS: In this study of community-dwelling stroke survivors,
      ethnic differences exist in the prevalence of stroke risk factors and income may
      explain the association between ethnicity and stroke.

PMID- 15961712
TI  - Houston paramedic and emergency stroke treatment and outcomes study (HoPSTO).
AB  - BACKGROUND AND PURPOSE: Establishment of stroke centers, combined with accurate
      paramedic diagnosis and rapid transport, is essential to deliver acute stroke
      therapy. We wanted to measure and improve paramedic and hospital performance
      through implementation of the Brain Attack Coalition and American Stroke
      Association guidelines. METHODS: Pre-intervention and active-intervention phases
      with parallel data measurement points were used. The study involved six hospitals
      comprising the majority of acute-stroke admissions in Houston, Tex. Hospital,
      paramedic, and patient data were collected prospectively pre-intervention and
      during the active-intervention phase on all suspected acute-stroke patients
      admitted by Houston Fire Department-Emergency Medical Services. A multilevel
      educational intervention included paramedic, hospital, and community education.
      Paramedic diagnostic accuracy, hospital-performance efficiency, and thrombolytic
      treatment rates were the main outcome measures of the study. RESULTS: Four
      hundred forty-six patients (74 per month) were transported in the pre
      intervention phase to participating hospitals (59.8% of all suspected stroke
      patients transported city wide by Houston Fire Department-Emergency Medical
      Services), compared with 1072 patients (89 per month, or 68.7%) transported in
      the active-intervention phase (P<0.001). Accuracy of paramedic diagnosis of
      stroke increased from 61% to 79%. Admission within 2 hours of symptom onset
      increased from 58% to 62% (P=0.002). Thrombolysis rates increased in 4 of 6
      centers, with 1 post- tissue plasminogen activator hemorrhage (3.7%) reported.
      CONCLUSIONS: A multilevel educational program improves rapid hospitalization and
      paramedic diagnostic accuracy and increases the number of patients presenting for
      evaluation within the 3-hour tissue plasminogen activator window. Stroke center
      development supports safe thrombolytic practice in community settings.

PMID- 15961713
TI  - The Early Systemic Prophylaxis of Infection After Stroke study: a randomized
      clinical trial.
AB  - BACKGROUND AND PURPOSE: Early infection after stroke is frequent but the clinical
      value of antibiotic prophylaxis in acute stroke has never been explored.
      OBJECTIVE AND METHODS: The Early Systemic Prophylaxis of Infection After Stroke
      (ESPIAS) is a randomized, double-blind, placebo-controlled study of antibiotic
      prophylaxis in patients older than 18 years with nonseptic ischemic or
      hemorrhagic stroke enrolled within 24 hours from clinical onset. Interventions
      included intravenous levofloxacin (500 mg/100 mL/d, for 3 days) or placebo (0.9%
      physiological serum) in addition to optimal care. A sample size of 240 patients
      was calculated to identify a 15% absolute risk reduction of the primary outcome
      measure, which was the incidence of infection at day 7 after stroke. Secondary
      outcome measures were neurological outcome and mortality at day 90. RESULTS:
      Based on a preplanned futility analysis, the study was interrupted prematurely
      when 136 patients had been included. Levofloxacin and placebo patients had a
      cumulative rate of infection of 6% and 6% (P=0.96) at day 1; 10% and 12% (P=0.83)
      at day 2; 12% and 15% (P=0.66) at day 3; 16% and 19% (P=0.82) at day 7; and 30%
      and 33% (P=0.70), at day 90. Using logistic regression, favorable outcome at day
      90 was inversely associated with baseline National Institutes of Health Stroke
      Scale (OR, 0.72; 95% CI, 0.59 to 0.89; P=0.002) and allocation to levofloxacin
      (OR, 0.19; 95% CI, 0.04 to 0.87; P=0.03). CONCLUSIONS: Prophylactic
      administration of levofloxacin (500 mg/100 mL/day for 3 days) is not better than
      optimal care for the prevention of infections in patients with acute stroke.

PMID- 15961714
TI  - Organized stroke care: the core of effective stroke care provision.

PMID- 15961715
TI  - Recommendations for comprehensive stroke centers: a consensus statement from the
      Brain Attack Coalition.
AB  - BACKGROUND AND PURPOSE: To develop recommendations for the establishment of
      comprehensive stroke centers capable of delivering the full spectrum of care to
      seriously ill patients with stroke and cerebrovascular disease. Recommendations
      were developed by members of the Brain Attack Coalition (BAC), which is a
      multidisciplinary group of members from major professional organizations involved
      with the care of patients with stroke and cerebrovascular disease. SUMMARY OF
      REVIEW: A comprehensive literature search was conducted from 1966 through
      December 2004 using Medline and Pub Med. Articles with information about clinical
      trials, meta-analyses, care guidelines, scientific guidelines, and other relevant
      clinical and research reports were examined and graded using established evidence
      based medicine approaches for therapeutic and diagnostic modalities. Evidence was
      also obtained from a questionnaire survey sent to leaders in cerebrovascular
      disease. Members of BAC reviewed literature related to their field and graded the
      scientific evidence on the various diagnostic and treatment modalities for
      stroke. Input was obtained from the organizations represented by BAC. BAC met on
      several occasions to review each specific recommendation and reach a consensus
      about its importance in light of other medical, logistical, and financial
      factors. CONCLUSIONS: There are a number of key areas supported by evidence-based
      medicine that are important for a comprehensive stroke center and its ability to
      deliver the wide variety of specialized care needed by patients with serious
      cerebrovascular disease. These areas include: (1) health care personnel with
      specific expertise in a number of disciplines, including neurosurgery and
      vascular neurology; (2) advanced neuroimaging capabilities such as MRI and
      various types of cerebral angiography; (3) surgical and endovascular techniques,
      including clipping and coiling of intracranial aneurysms, carotid endarterectomy,
      and intra-arterial thrombolytic therapy; and (4) other specific infrastructure
      and programmatic elements such as an intensive care unit and a stroke registry.
      Integration of these elements into a coordinated hospital-based program or system
      is likely to improve outcomes of patients with strokes and complex
      cerebrovascular disease who require the services of a comprehensive stroke
      center.

PMID- 15961716
TI  - Reperfusion-induced translocation of deltaPKC to cardiac mitochondria prevents
      pyruvate dehydrogenase reactivation.
AB  - Cardiac ischemia and reperfusion are associated with loss in the activity of the
      mitochondrial enzyme pyruvate dehydrogenase (PDH). Pharmacological stimulation of
      PDH activity improves recovery in contractile function during reperfusion.
      Signaling mechanisms that control inhibition and reactivation of PDH during
      reperfusion were therefore investigated. Using an isolated rat heart model, we
      observed ischemia-induced PDH inhibition with only partial recovery evident on
      reperfusion. Translocation of the redox-sensitive delta-isoform of protein kinase
      C (PKC) to the mitochondria occurred during reperfusion. Inhibition of this
      process resulted in full recovery of PDH activity. Infusion of the deltaPKC
      activator H2O2 during normoxic perfusion, to mimic one aspect of cardiac
      reperfusion, resulted in loss in PDH activity that was largely attributable to
      translocation of deltaPKC to the mitochondria. Evidence indicates that
      reperfusion-induced translocation of deltaPKC is associated with phosphorylation
      of the alphaE1 subunit of PDH. A potential mechanism is provided by in vitro data
      demonstrating that deltaPKC specifically interacts with and phosphorylates
      pyruvate dehydrogenase kinase (PDK)2. Importantly, this results in activation of
      PDK2, an enzyme capable of phosphorylating and inhibiting PDH. Thus,
      translocation of deltaPKC to the mitochondria during reperfusion likely results
      in activation of PDK2 and phosphorylation-dependent inhibition of PDH.

PMID- 15961717
TI  - Inhibition of Rho-kinase attenuates hypoxia-induced angiogenesis in the pulmonary
      circulation.
AB  - Pulmonary hypertension (PH) is a common complication of chronic hypoxic lung
      diseases, which increase morbidity and mortality. Hypoxic PH has previously been
      attributed to structural changes in the pulmonary vasculature including narrowing
      of the vascular lumen and loss of vessels, which produce a fixed increase in
      resistance. Using quantitative stereology, we now show that chronic hypoxia
      caused PH and remodeling of the blood vessel walls in rats but that this
      remodeling did not lead to structural narrowing of the vascular lumen. Sustained
      inhibition of the RhoA/Rho-kinase pathway throughout the period of hypoxic
      exposure attenuated PH and prevented remodeling in intra-acinar vessels without
      enlarging the structurally determined lumen diameter. In chronically hypoxic
      lungs, acute Rho kinase inhibition markedly decreased PVR but did not alter the
      alveolar to arterial oxygen gap. In addition to increased vascular resistance,
      chronic hypoxia induced Rho kinase-dependent capillary angiogenesis. Thus,
      hypoxic PH was not caused by fixed structural changes in the vasculature but by
      sustained vasoconstriction, which was largely Rho kinase dependent. Importantly,
      this vasoconstriction had no role in ventilation-perfusion matching and
      optimization of gas exchange. Rho kinase also mediated hypoxia-induced capillary
      angiogenesis, a previously unrecognized but potentially important adaptive
      response.

PMID- 15961718
TI  - Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces
      intramyocardial vasculopathy in apolipoprotein E-null mice.
AB  - Endothelial dysfunction induced by oxidized low-density lipoprotein (OxLDL) has
      been implicated in the pathogenesis of atherosclerosis and vasculopathy.
      Increased expression of lectin-like oxidized low-density lipoprotein receptor-1
      (LOX-1), the receptor for OxLDL in endothelial cells, has been demonstrated in
      the atherosclerotic plaques from experimental atherosclerotic animal models and
      human clinical samples. In vitro, activation of LOX-1 alters the expression of
      several endothelial cell genes that are involved in endothelial dysfunction. To
      investigate the role of LOX-1 in terms of both endothelial dysfunction and
      resultant vascular changes, we generated mice overexpressing LOX-1 (LOXtg) in
      C57BL/6 and apolipoprotein E-null mice (apoEKO) backgrounds. We found that the
      expression of the transgene was prominent in coronary vessels and cardiomyocytes.
      The enhancement of OxLDL uptake in LOXtg mice was consistent with the expression
      level of LOX-1. Under hyperlipidemic conditions, both OxLDL and 8-hydroxy-2'
      deoxyguanosine accumulated in the coronary arteries of LOXtg/apoEKO mice. The
      expression of ICAM-1 and VCAM-1, as well as the number of macrophages around
      blood vessels, were significantly increased in LOXtg/apoEKO mice compared with
      control littermates. There were no differences in either the hemodynamic profile
      or the plasma lipid profile between the 2 groups of animals. LOXtg/apoEKO mice
      displayed accelerated intramyocardial vasculopathy, and the atheroma-like lesion
      area was increased 10-fold in the LOXtg/apoEKO mice compared with nontransgenic
      littermates after 3-weeks on the high-fat diet. Thus, it is demonstrated that LOX
      1 overexpression promotes inflammatory intramyocardial vasculopathy in a
      hyperlipidemic mouse model, and this effect is probably mediated through the
      endothelial dysfunction induced by overexpression of LOX-1.

PMID- 15961719
TI  - Long-term and sustained COMP-Ang1 induces long-lasting vascular enlargement and
      enhanced blood flow.
AB  - Vascular enlargement is a characteristic feature of angiopoietin-1 (Ang1)-induced
      changes in adult blood vessels. However, it is unknown whether tissues having
      Ang1-mediated vascular enlargement have more blood flow or whether the
      enlargement is reversible. We have recently created a soluble, stable and potent
      Ang1 variant, COMP-Ang1. In the present study, we investigated the effects of
      varied dose and duration of COMP-Ang1 on vascular enlargement and blood flow in
      the tracheal microvasculature of adult mice and explored a possible mechanism of
      long-lasting vascular enlargement. We found that COMP-Ang1 administered by
      adenoviral vector induced long-lasting vascular enlargement and increased
      tracheal blood flow. In contrast, short-term administration of COMP-Ang1
      recombinant protein induced transient vascular enlargement that spontaneously
      reversed within a month. In both cases, the vascular enlargement resulted from
      endothelial proliferation. The COMP-Ang1-induced vascular remodeling is mediated
      mainly through Tie2 activation. Sustained overexpression of Tie2 could
      participate in the maintenance of vascular changes. Together, our findings
      indicate that sustained treatment with COMP-Ang1 can produce long-lasting
      vascular enlargement and increased blood flow.

PMID- 15961720
TI  - Expression of slow skeletal troponin I in adult mouse heart helps to maintain the
      left ventricular systolic function during respiratory hypercapnia.
AB  - Compared with the adult, neonatal heart muscle is less sensitive to deactivation
      by acidic pH. We hypothesized that expression of slow skeletal troponin I
      (ssTnI), the embryonic isoform, in adult heart would help maintain left
      ventricular (LV) systolic function during respiratory hypercapnia. We assessed LV
      function by transthoracic 2D-targeted M-mode and pulsed Doppler echocardiography
      in transgenic (TG) mice in which cardiac TnI was replaced with ssTnI and in
      nontransgenic (NTG) littermates. Anesthetized mice were ventilated with either
      100% oxygen or 35% CO2 balanced with oxygen. Arterial blood pH with 35% CO2
      decreased to the same levels in both groups of animals. In the absence of
      propranolol, the LV fractional shortening was higher in TG compared with NTG mice
      throughout most of the experimental protocol. LV diastolic function was impaired
      in TG compared with NTG mice both at 100% oxygen and 35% CO2 because E-to-A wave
      ratio of mitral flow was significantly lower, and E-wave deceleration time and LV
      isovolumic relaxation time were longer in TG compared with NTG mice. When
      compensatory mechanisms that occur through stimulation of beta-adrenergic
      receptors during hypercapnia were blocked by continuous perfusion with
      propranolol, we found that NTG mice died within 3 to 4 minutes after switching to
      35% CO2, whereas TG mice survived. Our experiments demonstrate the first evidence
      that specific replacement of cardiac TnI with ssTnI has a protective effect on
      the LV systolic function during hypercapnic acidosis in situ.

PMID- 15961721
TI  - Heterocellular contact at the myoendothelial junction influences gap junction
      organization.
AB  - Heterocellular communication between vascular smooth muscle cells (VSMC) and
      endothelial cells (EC) at the myoendothelial junction (MEJ) is a critical part of
      control of the arteriolar wall. We have developed an in vitro model of the MEJ
      composed of primary cultures of murine EC and VSMC. Immunoctytochemistry and
      immunoblots demonstrated Cx37 and Cx43 in both cell types, whereas Cx40 was found
      only in EC. Cx37 was excluded from the MEJ in both EC and VSMC. Connexin
      composition as well as functionality of the gap junctions at the MEJ was assessed
      by measuring diffusional transfer of biocytin and Cy3. Using connexin-specific
      blockers and manipulations of expression of individual connexin proteins, we
      confirmed that Cx37 is not a part of EC-VSMC coupling, and we demonstrated that
      heterotypic gap junctions are functional at the MEJ. We speculate that specific
      gap junction organization may be a vital component of EC-VSMC contact at the MEJ.

PMID- 15961722
TI  - Failure of bone marrow to reconstitute lung epithelium.
AB  - A new paradigm of epithelial tissue reconstitution has been suggested whereby
      circulating cells derived from bone marrow contribute to a variety of epithelial
      cell types. With regard to the lung, several recent reports have used
      immunofluorescence microscopy to demonstrate engraftment of bone marrow-derived
      cells as type II pneumocytes, the endogenous progenitors of the lung alveolus. We
      show here that immunofluorescence microscopy, as has been used in previous
      reports, cannot reliably identify rare engrafted cells in lung tissue sections
      after transplantation of bone marrow cells or purified hematopoietic stem cells
      tracked with ubiquitous labels. We have employed a lineage-specific reporter
      system based on transgenic mice that express the GFP reporter gene only in lung
      epithelial cells (surfactant protein C-GFP) to assay for engrafted cells by flow
      cytometry, histology, and molecular methods. Using this approach to evaluate
      transplant recipients, including those subjected to bleomycin-induced lung
      injury, we demonstrate that when autofluorescence, dead cells, and contaminating
      blood cells are excluded from analysis, there is no detectable reconstitution of
      lung alveolar epithelial cells by unfractionated bone marrow cells or purified
      hematopoietic stem cells.

PMID- 15961723
TI  - Cyr61 protects against hyperoxia-induced cell death via Akt pathway in pulmonary
      epithelial cells.
AB  - We have used gene expression profiling approaches to identify new molecular
      targets in various models of lung injury and human lung diseases. Among the many
      genes that are significantly induced in these studies, cysteine-rich61 (Cyr61)
      consistently ranks as one of the most significant genes. Here, we use the well
      established model of hyperoxia to better understand the function of Cyr61 in
      acute lung injury. Cyr61, a stress-related immediate-early response gene, has
      known diverse functions involving angiogenesis, tumorigenesis, and wound repair.
      It belongs to the newly discovered "CCN" family containing six growth and
      regulatory factors. We showed that hyperoxia induces Cyr61 expression in a
      variety of pulmonary cells and in lung tissue in vivo. Loss of function studies,
      by suppressing Cyr61 expression by siRNA, accelerated lung epithelial cell death
      after hyperoxia. Gain of function studies, by overexpressing Cyr61, significantly
      conferred increased resistance to hyperoxia-induced cell death. Moreover, cells
      overexpressing Cyr61 induce Akt activation. Inhibition of Akt by siRNA abrogated
      the protective effects of Cyr61-overexpressing cells in response to hyperoxia.
      Taken together, our data demonstrate that Cyr61 expression provides
      cytoprotection in hyperoxia-induced pulmonary epithelial cell death and that this
      effect was in part mediated via the Akt signaling pathway.

PMID- 15961724
TI  - Diacylglycerol-containing docosahexaenoic acid in acyl chain modulates airway
      smooth muscle tone.
AB  - We synthesized and assessed the role of a diacylglycerol (DAG)-containing
      docosahexaenoic acid (DHA), that is, 1-stearoyl-2-docosahexaenoyl-sn-glycerol
      (SDHG), in the contraction of guinea pig airway smooth muscle (ASM). We compared
      its action with 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) and 1,2-dioctanoyl-sn
      glycerol (1,2-DiC8), a stable DAG analog. The three DAGs (SAG, SDHG, and 1,2
      DiC8) induced reversible concentration-dependent contraction of ASM. SDHG induced
      higher guinea pig ASM contraction than did SAG and 1,2-DiC8. The effects of SDHG
      were blocked, to different extents, by nifedipine (L-type Ca2+ channel blocker).
      By employing GF-109203X (protein kinase C [PKC] inhibitor) and lanthanum (La3+),
      a nonselective cation channel blocker, we observed that SDHG evoked ASM
      contractile response via PKC-dependent and PKC-independent (but Ca2+-dependent)
      pathways. Interestingly, SAG exerted its action only by increasing [Ca2+]i and
      did not require PKC activation. To probe the implication of calcium mobilization,
      we employed thapsigargin (TG), which also induced ASM contraction in a calcium
      dependent manner. SDHG and 1,2-DiC8, in a PKC-dependent manner, induced the
      phosphorylation of CPI-17 (myosin light chain phosphatase inhibitor of 17 kD).
      Furthermore, SAG and TG failed to phosphorylate CPI-17 in ASM cells. Our results
      suggest that different DAG species, produced during a dietary supplementation
      with fatty acids, could modulate the reactivity of airway smooth muscles in a PKC
      dependent and -independent manner, and hence, may play a critical role in health
      and disease.

PMID- 15961725
TI  - Evidence that bone marrow cells do not contribute to the alveolar epithelium.
AB  - An ongoing controversy is the role of marrow cells in populating the alveolar
      epithelium. In this study, we employed flow cytometry and histologic techniques
      to evaluate this process. Donor bone marrow was harvested from transgenic mice
      expressing the LacZ or eGFP gene ubiquitously, or under the control of the human
      surfactant protein (SP)-C promoter, and transplanted into lethally irradiated,
      neonatal mice. In recipients transplanted with marrow that express eGFP or lacZ
      ubiquitously, light microscopy revealed cells whose morphology and location were
      compatible with a type II cell phenotype. Consistent with this, fluorescent
      microscopy suggested colocalization of eGFP and pro-SP-C proteins in single
      cells. In mice transplanted with SP-C-eGFP marrow, engraftment was not detectable
      by histology or flow cytometry. We therefore used deconvolution microscopy to
      reanalyze histologic sections that were thought to show marrow-derived type II
      cells. We found that all putative marrow-derived pneumocytes resulted from the
      overlapping fluorescent signals of an endogenous pro-SP-C+ type II cell and a
      donor-derived eGFP+ cell. Taken together, our observations underscore the
      technical difficulties associated with evaluating engraftment in lung, and argue
      against a contributory role for marrow cells in populating the alveolar
      epithelium.

PMID- 15961726
TI  - Interleukin-25 and interleukin-13 production by alveolar macrophages in response
      to particles.
AB  - Particle inhalation-induced lung inflammation acts as an adjuvant to allergens or
      respiratory viral infection in a process that is mediated by macrophages and
      epitheliums. The production of interleukin (IL)-4 and IL-13 by activated T cells
      is involved in the augmentation of Th2-type immune responses to particles, and IL
      25 induces the synthesis of IL-4 and IL-13. However, whether IL-13 and IL-25 are
      directly regulated by particle instillation in the lung has not been studied. The
      aim of this study was to reveal particle induction of IL-13 and IL-25 in the
      lung. TiO(2) instillation potently induced the mRNA expression for IL-25 and IL
      13 in lung tissue extracts 24 h after treatment, as compared with the sham group.
      Immunostaining for IL-25 and IL-13 showed strong positivity for macrophages in
      the inflammatory lung lesions of TiO(2)-treated rats. The alveolar macrophages
      expressed IL-25 and IL-13 24 h after in vitro stimulation with TiO(2) particles
      in dose- and time-dependent manners, with maximal induction at 24 and 48 h after
      stimulation, respectively. The sequence of the rat IL-25 gene is 95% homologous
      with the mouse IL-25 gene. These findings indicate that alveolar macrophages play
      an important role in particle-induced lung inflammation via direct induction of
      IL-13 and IL-25 production.

PMID- 15961728
TI  - Real-time investigation of nucleic acids phosphorylation process using molecular
      beacons.
AB  - Phosphorylation of nucleic acids is an indispensable process to repair strand
      interruption of nucleic acids. We have studied the process of phosphorylation
      using molecular beacon (MB) DNA probes in real-time and with high selectivity.
      The MB employed in this method is devised to sense the product of a
      'phosphorylation-ligation' coupled enzyme reaction. Compared with the current
      assays, this novel method is convenient, fast, selective, highly sensitive and
      capable of real-time monitoring in a homogenous solution. The preference of T4
      polynucleotide kinase (T4 PNK) has been investigated using this approach. The
      results revealed that a single-stranded oligonucleotide containing guanine at the
      5' termini is most preferred, while those utilizing cytosine in this location are
      least preferred. The preference of (T)9 was reduced greatly when phosphoryl was
      modified at the 5' end, implying that T4 PNK could discern the
      phosphorylated/unphosphorylated oligonucleotides. The increase of oligonucleotide
      DNA length leads to an enhancement in preference. A fast and accurate method for
      assaying the kinase activity of T4 PNK has been developed with a wide linear
      detection range from 0.002 to 4.0 U/ml in 3 min. The effects of certain factors,
      such as NTP, ADP, (NH4)2SO4 and Na2HPO4, on phosphorylation have been
      investigated. This novel approach enables us to investigate the interactions
      between proteins and nucleic acids in a homogenous solution, such as those found
      in DNA repair or in drug development.

PMID- 15961727
TI  - Constitutive and inducible expression of b7 family of ligands by human airway
      epithelial cells.
AB  - Activated T cells have been implicated in chronic rhinosinusitis (CRS) and asthma
      and physically interact with epithelial cells in the airways. We now report that
      human airway epithelial cells display significant constitutive cell-surface
      expression of costimulatory ligands, B7-H1, B7-H2, B7-H3, and B7-DC. Expression
      of B7-H1 and B7-DC was selectively induced by stimulation of either BEAS2B or
      primary nasal epithelial cells (PNEC) with interferon (IFN)-gamma (100 ng/ml).
      The combination of IFN-gamma and tumor necrosis factor-alpha (100 ng/ml)
      selectively induced expression better than IFN-gamma alone. Fluticasone treatment
      (10(-7) M) reduced the baseline expression and inhibited the induction of B7-H1
      and B7-DC in BEAS2B cells. In vitro exposure of PNEC to IFN-gamma also resulted
      in selective induction of B7-H1 and B7-DC. Monoclonal antibody blockade of B7-H1
      or B7-DC enhanced IFN-gamma expression by purified T cells in co-culture
      experiments, suggesting that these two B7 homologs inhibit T cell responses at
      the mucosal surface. Immunohistochemical staining of human sinonasal surgical
      tissue confirmed the presence of B7-H1, B7-H2, and B7-H3 in the epithelial cell
      layer, especially in samples from patients diagnosed with Samter's Triad, a
      severe form of CRS. Real-time PCR analysis of sinonasal tissue revealed elevated
      levels of B7-H1 and B7-DC in CRS compared with controls. These results
      demonstrate that epithelial cells express functional B7 costimulatory molecules
      and that expression of selected B7 family members is inducible in vitro and in
      vivo. Epithelial B7 homologs could play a role in regulation of lymphocytic
      activity at mucosal surfaces.

PMID- 15961729
TI  - Monitoring tat peptide binding to TAR RNA by solid-state 31P-19F REDOR NMR.
AB  - Complexes of the HIV transactivation response element (TAR) RNA with the viral
      regulatory protein tat are of special interest due in particular to the
      plasticity of the RNA at this binding site and to the potential for therapeutic
      targeting of the interaction. We performed REDOR solid-state NMR experiments on
      lyophilized samples of a 29 nt HIV-1 TAR construct to measure conformational
      changes in the tat-binding site concomitant with binding of a short peptide
      comprising the residues of the tat basic binding domain. Peptide binding was
      observed to produce a nearly 4 A decrease in the separation between
      phosphorothioate and 2'F labels incorporated at A27 in the upper helix and U23 in
      the bulge, respectively, consistent with distance changes observed in previous
      solution NMR studies, and with models showing significant rearrangement in
      position of bulge residue U23 in the bound-form RNA. In addition to providing
      long-range constraints on free TAR and the TAR-tat complex, these results suggest
      that in RNAs known to undergo large deformations upon ligand binding, 31P-19F
      REDOR measurements can also serve as an assay for complex formation in solid
      state samples. To our knowledge, these experiments provide the first example of a
      solid-state NMR distance measurement in an RNA-peptide complex.

PMID- 15961730
TI  - SW-ARRAY: a dynamic programming solution for the identification of copy-number
      changes in genomic DNA using array comparative genome hybridization data.
AB  - Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a
      technique capable of detecting deletions and duplications in genomes at high
      resolution. However, array CGH studies of the human genome noting false negative
      and false positive results using large insert clones as probes have raised
      important concerns regarding the suitability of this approach for clinical
      diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming
      algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for
      detecting copy-number changes in array CGH data. In a blind series of
      hybridizations to arrays consisting of the entire tiling path for the terminal 2
      Mb of human chromosome 16p, the method identified all monosomies between 267 and
      1567 kb with a high degree of statistical significance and accurately located the
      boundaries of deletions in the range 267-1052 kb. The approach is unique in
      offering both a nonparametric segmentation procedure and a nonparametric test of
      significance. It is scalable and well-suited to high resolution whole genome
      array CGH studies that use array probes derived from large insert clones as well
      as PCR products and oligonucleotides.

PMID- 15961732
TI  - Evolution of novel functions: cryptocyanin helps build new exoskeleton in Cancer
      magister.
AB  - Hemocyanin, the blue blood protein of many arthropods and molluscs, reversibly
      binds oxygen at its highly conserved copper-oxygen-binding sites and supplies
      tissues with oxygen. Cryptocyanin, closely related structurally and
      phylogenetically to arthropod hemocyanin, lacks several of the six critical
      copper-binding histidines, however, and has lost the ability to bind oxygen.
      Despite this loss of function, cryptocyanin continues to be synthesized, an
      indication that it has been exploited to carry out new functions. Here, we show
      that cryptocyanin is present in extremely high concentrations in the hemolymph of
      the crab during the premolt portion of the molt cycle. Both proteins are
      specifically expressed in the same type of cell in the hepatopancreas and
      secreted into the hemolymph, but cryptocyanin plays a major role in forming the
      new exoskeleton, while hemocyanin functions in oxygen transport. A cessation in
      cryptocyanin, but not hemocyanin, synthesis after eyestalk ablation supports our
      hypothesis that cryptocyanin is closely regulated by molting hormones. The
      contrasts between the two gene products illustrate how a gene duplication of a
      copper-oxygen protein and its subsequent mutation may work in concert with the
      evolution of new regulatory mechanisms, leading to the assumption of new
      functions.

PMID- 15961731
TI  - Triplex-induced recombination and repair in the pyrimidine motif.
AB  - Triplex-forming oligonucleotides (TFOs) bind DNA in a sequence-specific manner at
      polypurine/polypyrimidine sites and mediate targeted genome modification.
      Triplexes are formed by either pyrimidine TFOs, which bind parallel to the purine
      strand of the duplex (pyrimidine, parallel motif), or purine TFOs, which bind in
      an anti-parallel orientation (purine, anti-parallel motif). Both purine and
      pyrimidine TFOs, when linked to psoralen, have been shown to direct psoralen
      adduct formation in cells, leading to mutagenesis or recombination. However, only
      purine TFOs have been shown to mediate genome modification without the need for a
      targeted DNA-adduct. In this work, we report the ability of a series of
      pyrimidine TFOs, with selected chemical modifications, to induce repair and
      recombination in two distinct episomal targets in mammalian cells in the absence
      of any DNA-reactive conjugate. We find that TFOs containing N3'-->P5'
      phosphoramidate (amidate), 5-(1-propynyl)-2'-deoxyuridine (pdU), 2'-O-methyl
      ribose (2'-O-Me), 2'-O-(2-aminoethyl)-ribose, or 2'-O, 4'-C-methylene bridged or
      locked nucleic acid (LNA)-modified nucleotides show substantially increased
      formation of non-covalent triplexes under physiological conditions compared with
      unmodified DNA TFOs. However, of these modified TFOs, only the amidate and pdU
      modified TFOs mediate induced recombination in cells and stimulate repair in cell
      extracts, at levels comparable to those seen with purine TFOs in similar assays.
      These results show that amidate and pdU-modified TFOs can be used as reagents to
      stimulate site-specific gene targeting without the need for conjugation to DNA
      reactive molecules. By demonstrating the potential for induced repair and
      recombination with appropriately modified pyrimidine TFOs, this work expands the
      options available for triplex-mediated gene targeting.

PMID- 15961733
TI  - Intragel oxygen promotes hypoxia tolerance of scyphomedusae.
AB  - Populations of jellyfish are known to thrive in many low oxygen environments,
      however, the physiological mechanisms that permit these organisms to live in
      hypoxia remain unknown. The oxyregulatory abilities of four species of
      scyphomedusae were investigated, and it was found that Aurelia labiata,
      Phacellophora camtschatica, Cyanea capillata and Chrysaora quinquecirrha maintain
      steady oxygen consumption to below 20 hPa oxygen (<10% air saturation). Oxygen
      content of the mesoglea of A. labiata was measured using a fibre optic oxygen
      optode, and oxygen profiles through the gel are characterised by a gradient that
      decreases from just below normoxia at the aboral subsurface to approximately 85%
      air saturation near the subumbrellar musculature. This gradient sustains
      oxyregulation by scyphomedusae, and it is demonstrated that A. labiata must be
      using intragel oxygen to meet its metabolic needs. Gel can also be used as an
      oxygen reservoir when A. labiata moves into hypoxia. Gel oxygen is depleted after
      about 2 h in anoxia and recovers to 70% of normal after 2.5 h in normoxia.
      Behaviour experiments in the laboratory showed that Aurelia labiata behaves
      similarly in normoxia and hypoxia (30% and 18% air saturation). The acute
      threshold for provoking behavioural changes in A. labiata is somewhere near its
      critical partial pressure, and oxygen stratification stimulates swimming back and
      forth across the oxycline. Intragel oxygen dynamics are recognised as a
      fundamental component of medusan physiology.

PMID- 15961734
TI  - Regional and developmental variations of blood vessel morphometry in the chick
      embryo chorioallantoic membrane.
AB  - Avian eggs contain all the necessary materials for embryonic development except
      for oxygen, which diffuses in from the environment via pores in the hard,
      calcified eggshell to the chorioallantoic membrane (CAM), the respiratory organ,
      which is rich in blood vessels. An air cell is formed at the blunt pole of the
      egg between the two membranes of the eggshell and enlarges during incubation due
      to water vapor loss. In this study of the CAM of chicken eggs, we compared blood
      vessel numerical density [N(A(v))], area fraction of blood vessels [A(A(v))], CAM
      thickness (D(CAM)), total length of blood vessels (L) and surface area of the CAM
      attached to the eggshell (CAMre) with those under the air cell (CAMac) during
      incubation. We found that N(A(v)), A(A(v)), D(CAM) and L of the CAM increase with
      embryonic age and development. The N(A(v)), A(A(v)) and L under the air cell were
      higher in relation to the rest of the CAM at all ages tested, while the D(CAM)
      under the air cell was always lower than around the rest of the egg. Since the
      eggshell over the air cell has a relatively greater porosity, and the respiratory
      gas exchange ratio there is higher than at other areas of the egg, there is a
      correlation between all the above morphometric data and the eggshell porosity.
      This suggests optimization of embryonic gas exchange in the chicken egg. We would
      like to propose that, during natural incubation, an increased gas diffusion under
      the air cell, together with increased blood vessel numerical density, may
      compensate for covering of the central part of the eggshell by the incubating
      parent.

PMID- 15961735
TI  - Energy costs of blood digestion in a host-specific haematophagous parasite.
AB  - Fleas consume and digest blood from their hosts. We hypothesized that the energy
      costs of digestion of blood by fleas is dependent on the host species. To test
      this hypothesis, we studied CO2 emission, a measure of energy expenditure, during
      digestion of a blood meal taken by Parapulex chephrenis from a preferred (Acomys
      cahirinus) and a non-preferred (Gerbillus dasyurus) host. We predicted that the
      energy cost of digestion would be lower for A. cahirinus blood than that for G.
      dasyurus. Male and female fleas consumed similar amounts of blood per unit body
      mass, independent of host species. Our prediction was supported in that fleas
      expended significantly more energy digesting blood of G. dasyurus than blood of
      A. cahirinus. We also found CO2 emission rates of fed fleas were higher than
      those of unfed fleas and differed significantly among stages of blood digestion
      when a flea fed on G. dasyurus but not when it fed on A. cahirinus. When fed on
      G. dasyurus, fleas spent less energy during earlier than later stages of
      digestion.

PMID- 15961736
TI  - Laminin and the malaria parasite's journey through the mosquito midgut.
AB  - During the invasion of the mosquito midgut epithelium, Plasmodium ookinetes come
      to rest on the basal lamina, where they transform into the sporozoite-producing
      oocysts. Laminin, one of the basal lamina's major components, has previously been
      shown to bind several surface proteins of Plasmodium ookinetes. Here, using the
      recently developed RNAi technique in mosquitoes, we used a specific dsRNA
      construct targeted against the LANB2 gene (laminin gamma1) of Anopheles gambiae
      to reduce its mRNA levels, leading to a substantial reduction in the number of
      successfully developed oocysts in the mosquito midgut. Moreover, this molecular
      relationship is corroborated by the intimate association of developing P. berghei
      parasites and laminin in the gut, as observed using confocal microscopy. Our data
      support the notion of laminin playing a functional role in the development of the
      malaria parasite within the mosquito midgut.

PMID- 15961737
TI  - A method for deriving displacement data during cyclical movement using an
      inertial sensor.
AB  - Biomechanical studies often employ optical motion capture systems for the
      determination of the position of an object in a room-based coordinate system.
      This is not ideal for many types of study in locomotion since only a few strides
      may be collected per ;trial', and outdoor experiments are difficult with some
      systems. Here, we report and evaluate a novel approach that enables the user to
      determine linear displacements of a proprietary orientation sensor during
      cyclical movement. This makes experiments outside the constraints of the
      laboratory possible, for example to measure mechanical energy fluctuations of the
      centre of mass during over-ground locomotion. Commercial orientation sensors
      based on inertial sensing are small and lightweight and provide a theoretical
      framework for determining position from acceleration. In practice, the
      integration process is difficult to implement because of integration errors,
      integration constants and the necessity to determine the orientation of the
      measured accelerations. Here, by working within the constraints of cyclical
      movements, we report and evaluate a method for determining orientation and
      relative position using a modified version of a commercial inertial orientation
      sensor that combines accelerometers, gyroscopes and magnetometers, thus giving a
      full set of movement parameters (displacement, velocity and acceleration in three
      dimensions). The 35 g sensor was attached over the spine of a horse exercising on
      a treadmill. During canter locomotion (9.0 m s-1), the amplitudes of trunk
      movement in the x (craniocaudal), y (mediolateral) and z (dorsoventral)
      directions were 99.6, 57.9 and 140.2 mm, respectively. Comparing sensor
      displacement values with optical motion capture values for individual strides,
      the sensor had a median error (25th, 75th percentile) in the x, y and z
      directions of 0.1 (-9.7, +10.8), -3.8 (-15.5, +13.7) and -0.1 (-6.3, +7.1) mm,
      respectively. High-pass filtering of the displacement data effectively separated
      non-cyclical from cyclical components of the movement and reduced the
      interquartile ranges of the errors considerably to (-3.6, 6.2), (-4.0, 3.8) and (
      4.5, 5.1) for x, y and z displacement, respectively, during canter locomotion.
      This corresponds to (-3.2, 5.5)%, (-6.7, 6.3)% and (-3.3, 3.7)% of the range of
      motion.

PMID- 15961738
TI  - Habituated visual neurons in locusts remain sensitive to novel looming objects.
AB  - Many animals must contend with visual cues that provide information about the
      spatiotemporal dynamics of multiple objects in their environment. Much research
      has been devoted to understanding how an identified pair of interneurons in the
      locust, the Descending Contralateral Movement Detectors (DCMDs), respond to
      objects on an impending collision course. However, little is known about how
      these neurons respond when challenged with multiple, looming objects of different
      complex shapes. I presented locusts with objects resembling either another locust
      or a bird approaching on a direct collision course at 3 m s-1 while recording
      from the DCMD axon within the mesothoracic ganglion. Stimulus presentations were
      designed to test: (i) whether DCMD habituation was related to the frequency of
      approach, (ii) if habituated DCMDs were able to respond to a novel stimulus and
      (iii) if non-looming motion within complex objects (internal object motion)
      during approach affects habituation. DCMD responses to simulated locusts or birds
      habituated more when the time interval between consecutive approaches within
      similar sequences decreased from 34 s to 4 s. Strongly habituated DCMDs were,
      however, able to respond to the same object approaching along a new trajectory or
      to a larger object approaching along the same trajectory. Habituation was not
      affected by internal object motion. These data are consistent with earlier
      findings that DCMD habituation occurs at localized synapses, which permits
      maintained sensitivity to multiple objects in the animal's environment.

PMID- 15961739
TI  - The metabolic cost of egg production is repeatable.
AB  - The metabolic cost of egg production in birds (passerines) has been measured as a
      16-27% increase in basal or resting metabolic rate (BMR and RMR, respectively)
      when comparing non-breeding values with those in egg-producing individuals.
      However, available data to date have been obtained in free-living birds and may
      thus be confounded by the effect of variable ecological conditions on non
      reproductive physiological machinery (organ mass or metabolic activity) which
      might contribute to measured variation in RMR. Here, we show that in captive,
      controlled conditions, the process of egg formation induces a 22% increase in RMR
      in female zebra finches Taeniopygia guttata. Among individuals, variation in
      laying RMR is independent of egg mass, clutch size or total clutch mass.
      Importantly, we show that individual variation in both non-breeding and laying
      RMR is repeatable over periods of at least 8-10 months, i.e. individual variation
      in RMR remained constant over time for any given physiological state. This
      suggests that the metabolic cost of egg formation should respond to selection.
      However, we also show that in males, but not females, repeatability of RMR
      declines over time even when birds are kept in constant controlled conditions.

PMID- 15961740
TI  - Burst characteristics of daily jaw muscle activity in juvenile rabbits.
AB  - Muscle activation varies with different behaviors and can be quantified by the
      level and duration of activity bursts. Jaw muscles undergo large anatomical
      changes during maturation, which are presumably associated with changes in daily
      muscle function. Our aim was to examine the daily burst number, burst length
      distribution and duty time (fraction of the day during which a muscle was active)
      of the jaw muscles of juvenile male rabbits (Oryctolagus cuniculus). A radio
      telemetric device was implanted to record muscle activity continuously from the
      digastric, superficial and deep masseter, medial pterygoid and temporalis during
      maturation week 9-14. Daily burst characteristics and duty times were determined
      for activations, including both powerful and non-powerful motor behavior. All
      muscles showed constant burst numbers, mean burst lengths and duty times during
      the recording period. Including all behavior, the temporalis showed significantly
      larger daily burst numbers (205,000) and duty times (18.2%) than the superficial
      and deep masseter (90,000; 7.5%). Burst numbers and duty times were similar for
      the digastric (120,000; 11.1%) and medial pterygoid (115,000; 10.4%). The
      temporalis and deep masseter showed many short low activity bursts (0.05 s), the
      digastric showed many long bursts (0.09 s). For activations during powerful
      behaviors the superficial masseter and medial pterygoid had the largest burst
      numbers and duty times. Both muscles showed similar burst characteristics for all
      activation levels. It was concluded that activation of the jaw muscles is
      differently controlled during powerful and non-powerful motor behaviors and the
      functional organization of motor control patterns does not vary from 9 to 14
      weeks of age.

PMID- 15961741
TI  - Emperor penguins adjust swim speed according to the above-water height of ice
      holes through which they exit.
AB  - Emperor penguins leap from the water onto the sea ice. Their ability to reach
      above-water height depends critically on initial vertical speed of their leaping,
      assuming that the kinetic energy is converted to gravitational potential energy.
      We deliberately changed the above-water heights of ice hole exits, in order to
      examine whether penguins adjusted swim speed in accordance with the above-water
      height of the ice. Penguins were maintained in a corral on the fast ice in
      Antarctica, and voluntarily dived through two artificial ice holes. Data loggers
      were deployed on the penguins to monitor under water behavior. Nine instrumented
      penguins performed 386 leaps from the holes during experiments. The maximum swim
      speeds within 1 s before the exits through the holes correlated significantly
      with the above-water height of the holes. Penguins adopted higher speed to exit
      through the higher holes than through the lower holes. Speeds of some failed
      exits were lower than the theoretical minimum values to reach a given height.
      Penguins failed to exit onto the sea ice in a total of 37 of the trials. There
      was no preference to use lower holes after they failed to exit through the higher
      holes. Rather, swim speed was increased for subsequent attempts after failed
      leaps. These data demonstrated that penguins apparently recognized the above
      water height of holes and adopted speeds greater than the minimal vertical speeds
      to reach the exit height. It is likely, especially in the case of higher holes
      (>40 cm), that they chose minimum speeds to exit through the holes to avoid
      excess energy for swimming before leaping. However, some exceptionally high
      speeds were recorded when they directly exited onto the ice from lower depths. In
      those cases, birds could increase swim speed without strokes for the final
      seconds before exit and they only increased the steepness of their body angles as
      they surfaced, which indicates that the speed required for leaps by emperor
      penguins were aided by buoyancy, and that penguins can sometimes exit through the
      ice holes without any stroking effort before leaping.

PMID- 15961742
TI  - Adhesion of echinoderm tube feet to rough surfaces.
AB  - Echinoderms attach strongly and temporarily to the substratum by means of
      specialized organs, the podia or tube feet. The latter consist of a basal
      extensible cylinder, the stem, which bears an apical flattened disc. The disc
      repeatedly attaches to and detaches from the substratum through adhesive and de
      adhesive secretions. In their activities, echinoderms have to cope with substrata
      of varying degrees of roughness as well as with changing hydrodynamic conditions,
      and therefore their tube feet must adapt their attachment strength to these
      environmental constraints. This study is the first attempt to evaluate the
      influence of substratum roughness on the temporary adhesion of echinoderm tube
      feet and to investigate the material properties of their contact surface. It was
      demonstrated that tube foot discs are very soft (E-modulus of 6.0 and 8.1 kPa for
      sea stars and sea urchins, respectively), have viscoelastic properties and adapt
      their surface to the substratum profile. They also show increased adhesion on a
      rough substratum in comparison to its smooth counterpart, which is due mostly to
      an increase in the geometrical area of contact between the disc and the surface.
      Tenacity (force per unit area) increases with roughness [e.g. 0.18 and 0.34 MPa
      on smooth polymethyl-methacrylate (PMMA), 0.21 and 0.47 MPa on rough PMMA for sea
      stars and sea urchins, respectively] if only the projected surface area of the
      adhesive footprint is considered. However, if this tenacity is corrected to take
      into account the actual substratum 3-D profile, surface roughness no longer
      influences significantly the corrected adhesion strength (e.g. 0.18 and 0.34 MPa
      on smooth PMMA, 0.19 and 0.42 MPa on rough PMMA for sea stars and sea urchins,
      respectively). It can be hypothesized that, under slow self-imposed forces, disc
      material behaves viscously to adapt to substratum roughness while the adhesive
      fills out only very small surface irregularities (in the nanometer range). It is
      deposited as a thin film ideal for generation of strong adhesion. Under short
      pulses of wave-generated forces, attached discs probably behave elastically,
      distributing the stress along the entire contact area, in order to avoid crack
      generation and thus precluding disc peeling and tube foot detachment.

PMID- 15961743
TI  - Life at acidic pH imposes an increased energetic cost for a eukaryotic
      acidophile.
AB  - Organisms growing in acidic environments, pH<3, would be expected to possess
      fundamentally different molecular structures and physiological controls in
      comparison with similar species restricted to neutral pH. We begin to investigate
      this premise by determining the magnitude of the transmembrane electrochemical H+
      gradient in an acidophilic Chlamydomonas sp. (ATCC PRA-125) isolated from the Rio
      Tinto, a heavy metal laden, acidic river (pH 1.7-2.5). This acidophile grows most
      rapidly at pH 2 but is capable of growth over a wide pH range (1.5-7.0), while
      Chlamydomonas reinhardtii is restricted to growth at pH>or=3 with optimal growth
      between pH 5.5 and 8.5. With the fluorescent H+ indicator, 2',7'-bis-(2
      carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that the acidophilic
      Chlamydomonas maintains an average cytosolic pH of 6.6 in culture medium at both
      pH 2 and pH 7 while Chlamydomonas reinhardtii maintains an average cytosolic pH
      of 7.1 in pH 7 culture medium. The transmembrane electric potential difference of
      Chlamydomonas sp., measured using intracellular electrodes at both pH 2 and 7, is
      close to 0 mV, a rare value for plants, animals and protists. The 40,000-fold
      difference in [H+] could be the result of either active or passive mechanisms.
      Evidence for active maintenance was detected by monitoring the rate of ATP
      consumption. At the peak, cells consume about 7% more ATP per second in medium at
      pH 2 than at pH 7. This increased rate of consumption is sufficient to account
      for removal of H+ entering the cytosol across a membrane with relatively high
      permeability to H+ (7x10(-8) cm s-1). Our results indicate that the small
      increase in the rate of ATP consumption can account for maintenance of the
      transmembrane H+ gradient without the imposition of cell surface H+ barriers.

PMID- 15961744
TI  - Do seasonal changes in metabolic rate facilitate changes in diving behaviour?
AB  - Macaroni penguins were implanted with data loggers to record heart rate (fH),
      abdominal temperature (Tab) and diving depth during their pre-moult trip (summer)
      and winter migration. The penguins showed substantial differences in diving
      behaviour between the seasons. During winter, mean and maximum dive duration and
      dive depth were significantly greater than during summer, but the proportion of
      dives within the calculated aerobic dive limit (cADL) did not change. Rates of
      oxygen consumption were estimated from fH. As winter progressed, the rate of
      oxygen consumption during dive cycles (sVO2DC)) declined significantly and
      mirrored the pattern of increase in maximum duration and depth. The decline in
      sVO2DC) was matched by a decline in minimum rate of oxygen consumption
      (sVO2min)). When sVO2min) was subtracted from sVO2DC), the net cost of diving was
      unchanged between summer and winter. We suggest that the increased diving
      capacity demonstrated during the winter was facilitated by the decrease in
      sVO2min). Abdominal temperature declined during winter but this was not
      sufficient to explain the decline in sVO2min). A simple model of the interactions
      between sVO2min), thermal conductance and water temperature shows how a change in
      the distribution of fat stores and therefore a change in insulation and/or a
      difference in foraging location during winter could account for the observed
      reduction in sVO2min) and hence sVO2DC).

PMID- 15961745
TI  - Physiological responses to feeding, fasting and estivation for anurans.
AB  - Anuran estivation is characterized by long episodes of aphagia. To investigate
      whether estivating anurans downregulate intestinal performance as an adaptive
      mechanism to reduce energy expenditure, I compared the metabolic and intestinal
      responses to feeding, fasting and estivation among non-estivating and estivating
      species of the anuran families Bufonidae, Leptodactylidae and Ranidae. Standard
      metabolic rates of the estivating Bufo alvarius, Ceratophrys ornata and
      Pyxicephalus adspersus were significantly less than those of the non-estivating
      Bufo marinus, Leptodactylus pentadactylus and Rana catesbeiana. Whereas the
      digestion of rodent meals equaling 15% of anuran body mass generated significant
      metabolic responses for all species, specific dynamic action was significantly
      greater for the estivating species. For estivating species, feeding triggered
      more than a doubling of small intestinal mass and significant upregulation of
      intestinal nutrient transport rates, resulting in six- to tenfold increases in
      total intestinal nutrient uptake capacity. The postprandial intestinal responses
      of the non-estivating species were much more modest, averaging a 50% increase in
      small intestinal mass and 69% increase in uptake capacities. Following 1 month of
      laboratory-induced estivation, C. ornata and P. adspersus had further depressed
      metabolic rates by 20%, intestinal masses by 44%, and total intestinal uptake
      capacities by 60%. In a fashion similar to infrequently feeding, sit-and-wait
      foraging snakes, estivating anurans possess the capacity to severely downregulate
      intestinal performance with fasting and estivation, and subsequently upregulate
      the gut with feeding. The depression in gut performance during estivation aids in
      reducing energy expenditure, thereby increasing the duration that the animal can
      remain dormant while relying solely upon stored energy.

PMID- 15961746
TI  - Antifreeze activity in the gastrointestinal fluids of Arctogadus glacialis
      (Peters 1874) is dependent on food type.
AB  - The influence of two food types, Boreogadus saida (Bs) and crustaceans (Cr), on
      the osmolality, ion concentrations, antifreeze activity and antifreeze
      glycoprotein (AFGP) distribution in the gastrointestinal fluids of the Arctic
      gadoid Arctogadus glacialis was determined. The gastrointestinal fluids were
      hyperosmotic to serum but no significant differences in osmolality were found
      between the two food types. The food type significantly affected the antifreeze
      activity of the mid-gut fluids. The hysteresis freezing points, -3.27+/-0.30
      degrees C and -2.44+/-0.11 degrees C for B. saida and crustaceans, respectively,
      were significantly lower than that of serum (-1.99+/-0.07 degrees C).
      Furthermore, an exceptionally large thermal hysteresis ranging from 1.47+/-0.19
      degrees C to 2.04+/-0.30 degrees C was observed in the intestinal fluids of fish
      feeding on B. saida. Native gel electrophoresis revealed that the
      gastrointestinal fluids contained AFGPs in all the different size groups.
      However, differences in band intensities for the two food types suggest that the
      ingested food has an influence on the concentration of the different AFGP-sizes
      in these fluids. A decrease in band intensities combined with a drop in thermal
      hysteresis from mid-gut to hind-gut fluid suggests that absorption of AFGP or
      possibly degradation occur during digestion.

PMID- 15961747
TI  - Low temperature acclimated populations of the grain aphid Sitobion avenae retain
      ability to rapidly cold harden with enhanced fitness.
AB  - In contrast to previous studies of rapid cold-hardening (RCH), which have
      investigated the responses of insects maintained under 'summer conditions' (20
      degrees to 25 degrees C), this study focuses on the ability of low-temperature
      acclimated insects to undergo RCH. When the grain aphid Sitobion avenae Fabricus
      was low-temperature acclimated by rearing for three generations at 10 degrees C,
      the discriminating temperatures (temperature that results in approximately 20%
      survival after direct transfer from the rearing temperature to a sub-zero
      temperature for a period of 3 h), of first instar nymphs and adult aphids were 
      11.5 degrees and -12 degrees C, respectively. Maximum rapid cold-hardening was
      induced by cooling aphids at 0 degrees C for 2 h (nymphs) or 30 min (adults),
      resulting in survival at the respective discriminating temperatures increasing
      from 26% to 96% (nymphs) and 22% to 70% (adults). Cooling from 10 degrees to 0
      degrees C at 1 degree, 0.1 degrees and 0.05 degrees C min-1 significantly
      increased survival of nymphs at the discriminating temperature, but not of
      adults. There were no ;ecological costs' associated with rapid cold-hardening at
      0 degrees C, or with exposure of rapidly cold-hardened aphids to the
      discriminating temperatures; fecundity and longevity, in both nymphs and adults
      were either similar to control aphids or significantly increased. The study
      demonstrates that rapid cold-hardening ability is retained in aphids that have
      already undergone cold-acclimation, as would be the case in overwintering aphids.
      Both rapid cold-hardening and subsequent exposure at previously lethal
      temperatures can enhance fitness in surviving individuals.

PMID- 15961748
TI  - Fetal alcohol syndrome prevention in South Africa and other low-resource
      countries.

PMID- 15961749
TI  - Drinking and intimate partner violence in a changing society.

PMID- 15961751
TI  - Addressing the growing burden of trauma and injury in low- and middle-income
      countries.

PMID- 15961750
TI  - The World Bank: global health or global harm?

PMID- 15961752
TI  - Health communication, intelligence, and health differentials.

PMID- 15961754
TI  - "Whistle while you work": a historical account of some associations among music,
      work, and health.
AB  - Music has long been a uniting force among workers. Music can improve team spirit
      and provide an enjoyable diversion, but it is most useful in expressing the true
      feelings of a sometimes desperate community. Over time, a variety of musical
      media have emerged to match the prevailing conditions at work: the folk songs of
      19th-century handloom weavers, the songs of industrial Britain's trade union
      members, the workers' radio programs of the 1940s. Associations have arisen to
      encourage and coordinate musical activities among workers, and public awareness
      of the hazards of some occupations has been promoted through music.

PMID- 15961753
TI  - The trouble with "MSM" and "WSW": erasure of the sexual-minority person in public
      health discourse.
AB  - Men who have sex with men (MSM) and women who have sex with women (WSW) are
      purportedly neutral terms commonly used in public health discourse. However, they
      are problematic because they obscure social dimensions of sexuality; undermine
      the self-labeling of lesbian, gay, and bisexual people; and do not sufficiently
      describe variations in sexual behavior.MSM and WSW often imply a lack of lesbian
      or gay identity and an absence of community, networks, and relationships in which
      same-gender pairings mean more than merely sexual behavior. Overuse of the terms
      MSM and WSW adds to a history of scientific labeling of sexual minorities that
      reflects, and inadvertently advances, heterosexist notions. Public health
      professionals should adopt more nuanced and culturally relevant language in
      discussing members of sexual-minority groups.

PMID- 15961755
TI  - American College of Radiology Imaging Network digital mammographic imaging
      screening trial: objectives and methodology.
AB  - This study was approved by the Institutional Review Board (IRB) of the American
      College of Radiology Imaging Network (ACRIN) and each participating site and by
      the IRB and the Cancer Therapy Evaluation Program at the National Cancer
      Institute. The study was monitored by an independent Data Safety and Monitoring
      Board, which received interim analyses of data to ensure that the study would be
      terminated early if indicated by trends in the outcomes. The ACRIN, which is
      funded by the National Cancer Institute, conducted the Digital Mammographic
      Imaging Screening Trial (DMIST) primarily to compare the diagnostic accuracy of
      digital and screen-film mammography in asymptomatic women presenting for
      screening for breast cancer. Over the 25.5 months of enrollment, a total of 49
      528 women were included at the 33 participating sites, which used five different
      types of digital mammography equipment. All participants underwent both screen
      film and digital mammography. The digital and screen-film mammograms of each
      subject were independently interpreted by two radiologists. If findings of either
      examination were interpreted as abnormal, subsequent work-up occurred according
      to the recommendations of the interpreting radiologist. Breast cancer status was
      determined at biopsy or follow-up mammography 11-15 months after study entry. In
      addition to the measurement of diagnostic accuracy by using the interpretations
      of mammograms at the study sites, DMIST included evaluations of the relative cost
      effectiveness and quality-of-life effects of digital versus screen-film
      mammography. Six separate reader studies using the de-identified archived DMIST
      mammograms will also assess the diagnostic accuracy of each of the individual
      digital mammography machines versus screen-film mammography machines, the effect
      of breast density on diagnostic accuracy of digital and screen-film mammography,
      and the effect of different rates of breast cancer on the diagnostic accuracy in
      a reader study.

PMID- 15961756
TI  - Cancer patients' and patient advocates' perspectives on a novel information
      source: a qualitative study of the art of oncology, when the tumor is not the
      target.

PMID- 15961757
TI  - Improved response in high-risk neuroblastoma with protracted topotecan
      administration using a pharmacokinetically guided dosing approach.
AB  - PURPOSE: To estimate the response rate and toxicity associated with intravenous
      topotecan when it is administered on a protracted schedule according to a
      pharmacokinetically guided dosing approach to treat childhood high-risk
      neuroblastoma. PATIENTS AND METHODS: In this prospective phase II trial,
      topotecan was administered intravenously daily for 5 days for each of 2
      consecutive weeks for two cycles. On the basis of topotecan systemic clearance,
      doses were individualized to attain a single-day topotecan lactone area under the
      plasma concentration-time curve (AUC) of 80 to 120 ng/mL . h. Patients
      subsequently received standard treatment. RESULTS: Both cycles were administered
      to 28 (93%) of the 30 enrolled patients (median age, 3.1 years). Target topotecan
      AUCs were achieved in 92 (72%) of the 127 measurements conducted after
      pharmacokinetically guided adjustment; the median dosage required to achieve
      target AUCs was 2.7 mg/m(2) (range, 0.95 to 3.8 mg/m(2)). The response rate was
      60% (95% CI, 41% to 77%); there were one complete and 17 partial responses. No
      patient experienced disease progression during initial topotecan therapy. Primary
      tumor volumes decreased (median decrease, -58.2%; range, -95.1% to -4.9%) in the
      26 patients with available size data. Homovanillic acid levels in 16 (89%) of 18
      patients and vanillylmandelic acid levels in 14 (78%) of 18 patients were lower
      (P = .002 and P = .018, respectively) after topotecan therapy. Reversible grade 4
      myelosuppression occurred in all patients, but no deaths occurred as a result of
      infection or toxicity. CONCLUSION: Topotecan is active against neuroblastoma when
      it is administered on a protracted schedule and targeted systemic exposure is
      achieved.

PMID- 15961758
TI  - Impact of latent Epstein-Barr virus infection on outcome in children and
      adolescents with Hodgkin's lymphoma.
AB  - PURPOSE: The prognostic significance of latent Epstein-Barr virus (EBV) infection
      in Hodgkin's lymphoma (HL) is debated controversially. Especially in the
      pediatric age group, no conclusive data are available. PATIENTS AND METHODS:
      Eight hundred forty-two children and adolescents (median age, 13.7 years) from
      pediatric multicenter treatment studies HD-90 and HD-95 were studied for latent
      EBV infection in Hodgkin's and Reed-Sternberg cells by immunostaining against
      latent membrane protein 1 (LMP-1). Results were compared with established risk
      factors. RESULTS: Two hundred sixty-three patients (31%) were LMP positive. EBV
      infection correlated with sex (39% male v 23% female; P < .001), histologic
      subtype (69% mixed cellularity v 22% nodular sclerosis v 6% lymphocyte
      predominance; P < .001) and young age. With a median follow-up of 4.9 years, 820
      patients (97%) are alive. Probability of overall survival at 10 years (+/-
      standard deviation) for EBV-negative and -positive patients was 98.1% +/- 0.6%
      and 95.1% +/- 1.4%, respectively (P = .017 by log-rank test). A negative effect
      of EBV infection became evident for patients with nodular sclerosis subtype
      Bennett II (P = .02), and those treated for advanced stages (P = .003). In
      multivariate analysis, LMP positivity was an independent factor for adverse
      outcome (RR = 3.08). Probability of failure-free survival (FFS) in LMP positive
      and negative patients was 89.1% +/- 2.3% and 84.1% +/- 3.9%, respectively (P =
      .86). CONCLUSION: With effective combined treatment modalities in pediatric HL,
      latent EBV infection has no influence on FFS but is associated with an inferior
      overall survival in crucial subgroups.

PMID- 15961759
TI  - Phase III randomized multicenter study of a humanized anti-CD33 monoclonal
      antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone
      in patients with refractory or first-relapsed acute myeloid leukemia.
AB  - PURPOSE: Lintuzumab (HuM195) is an unconjugated humanized murine monoclonal
      antibody directed against the cell surface myelomonocytic differentiation antigen
      CD33. In this study, the efficacy of lintuzumab in combination with induction
      chemotherapy was compared with chemotherapy alone in adults with first relapsed
      or primary refractory acute myeloid leukemia (AML). PATIENTS AND METHODS:
      Patients with relapsed or primary resistant AML (duration of first response, zero
      to 12 months) were randomly assigned to receive either mitoxantrone 8 mg/m(2),
      etoposide 80 mg/m(2), and cytarabine 1 g/m(2) daily for 6 days (MEC) in
      combination with lintuzumab 12 mg/m(2), or MEC alone. Overall response, defined
      as the rate of complete remission (CR) and CR with incomplete platelet recovery
      (CRp), was the primary end point of the study, with additional analyses of
      survival time and toxicity. RESULTS: A total of 191 patients were randomly
      assigned from November 1999 to April 2001. The percent CR plus CRp with MEC plus
      lintuzumab was 36% v 28% in patients treated with MEC alone (P = .28). The
      overall median survival was 156 days and was not different in the two arms of the
      study. Apart from mild antibody infusion-related toxicities (fever, chills, and
      hypotension), no differences in chemotherapy-related adverse effects, including
      hepatic and cardiac dysfunction, were observed with the addition of lintuzumab to
      induction chemotherapy. CONCLUSION: The addition of lintuzumab to salvage
      induction chemotherapy was safe, but did not result in a statistically
      significant improvement in response rate or survival in patients with
      refractory/relapsed AML.

PMID- 15961760
TI  - Use of magnetic resonance imaging to assess blood-brain/blood-glioma barrier
      opening during conformal radiotherapy.
AB  - PURPOSE: For chemotherapy to act synergistically and safely with radiation
      against high-grade gliomas, drugs must pass the endothelial junctions of the
      blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood
      brain barrier (BBB) to cause toxicity to normal brain. The objective of this
      study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during
      a course of radiotherapy of high-grade gliomas. PATIENTS AND METHODS: Sixteen
      patients with grade 3 or 4 supratentorial malignant glioma receiving conformal
      radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after
      completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)
      uptake index was analyzed with respect to the tumor and RT dose received.
      RESULTS: In the nonenhanced tumor region, contrast uptake increased significantly
      after the receipt of approximately 10 Gy (P < .01), and reached a maximum after
      the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor
      region, contrast uptake decreased over the course of RT and became significant
      after completion of RT in patients without progressive disease. The healthy brain
      showed only nonsignificant changes during and after irradiation. CONCLUSION:
      Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced
      tumor region but not in the remaining brain during the course of RT, suggesting
      opening of the BTB. This finding suggests that the effect of conformal radiation
      is more selective on the BTB than the BBB, and there may be a window extending
      from 1 week after the initiation of radiotherapy to 1 month after the completion
      of treatment during which a pharmaceutical agent has maximum access to high-grade
      gliomas.

PMID- 15961761
TI  - Randomized trial of neoadjuvant chemotherapy comparing paclitaxel, ifosfamide,
      and cisplatin with ifosfamide and cisplatin followed by radical surgery in
      patients with locally advanced squamous cell cervical carcinoma: the SNAP01
      (Studio Neo-Adjuvante Portio) Italian Collaborative Study.
AB  - PURPOSE: Neoadjuvant chemotherapy may represent an alternative to irradiation in
      locally advanced squamous cell cervical cancer. Aims of this study were to
      compare a three-drug (paclitaxel, ifosfamide, and cisplatin [TIP]) with a two
      drug (ifosfamide and cisplatin [IP]) regimen and to assess the prognostic value
      of pathologic response on survival. PATIENTS AND METHODS: Patients (n = 219) were
      randomly assigned to ifosfamide 5 g/m(2) during 24 hours plus cisplatin 75
      mg/m(2), or paclitaxel 175 mg/m(2) plus ifosfamide 5 g/m(2) during 24 hours and
      cisplatin 75 mg/m(2) every 3 weeks for three courses. RESULTS: Grades 3 to 4
      neutropenia, anemia, and thrombocytopenia were more frequent with TIP. We
      recorded four deaths related to toxicity. The optimal pathologic response (OPT)
      rate (residual disease < 3 mm stromal invasion) was higher with TIP than with IP
      (48% v 23%; odds ratio, 3.22; 95% CI, 1.69 to 5.88; P = .0003). At a median
      follow-up of 43.4 months, 79 women experienced disease progression or died (46 in
      the IP arm, 33 in the TIP arm). Patients receiving TIP experienced a treatment
      failure rate 25% less than those receiving IP, but this difference was not
      statistically significant (hazard ratio [HR], 0.75; 95% CI, 0.48 to 1.17; P =
      .20). Sixty-one patients died (37 in the IP arm, 24 in the TIP arm), and the HR
      of death was in favor of TIP, although not significantly (HR, 0.66; 95% CI, 0.39
      to 1.10; P = .11). In patients assessable for response (n = 189), the average
      death rates were higher in the group that did not achieve OPT (HR, 5.88; 95% CI,
      2.50 to 13.84; P < .0001). CONCLUSION: The TIP regimen is associated with a
      higher response rate than the IP regimen, without a statistically significant
      effect on overall survival. OPT was a prognostic factor for survival.

PMID- 15961762
TI  - Achieving optimal outcomes after radical prostatectomy.
AB  - PURPOSE: The most favorable outcome that can be achieved after radical
      prostatectomy is complete tumor resection without recurrence and full recovery of
      continence and potency. Risks of erectile dysfunction, incontinence, and disease
      recurrence are well described, but in isolation, do not adequately inform
      patients of the possibility of becoming cancer-free while at the same time
      returning to their preoperative functional state. We sought to determine the
      frequency of optimal outcomes after radical prostatectomy and the time to such
      outcomes. PATIENTS AND METHODS: Patients who underwent radical prostatectomy
      performed at a tertiary referral center between July 1998 and July 2003 for
      clinical stage T1 to T3 prostate cancer were identified. Patients were excluded
      if they were incontinent or impotent preoperatively, or if they had received
      radiotherapy or neoadjuvant androgen deprivation therapy previously. Six hundred
      forty-seven patients were analyzed for time to recovery of full continence and
      potency without cancer recurrence after surgery. Optimal outcome probability was
      calculated with a Markov state transition model to simulate clinical outcomes in
      the first 4 years following radical prostatectomy. RESULTS: Mean patient age was
      58 years, and mean pretreatment prostate-specific antigen was 6.9 ng/mL. Cancer
      free status with full continence and potency was achieved in 30% of men at 12
      months, 42% at 24 months, 47% at 36 months, and 53% at 48 months postoperatively.
      CONCLUSION: Optimal outcomes after radical prostatectomy can be achieved in a
      small majority of cases. Time to full recovery is primarily dictated by recovery
      of erectile function. This information is helpful for patients interested in
      their chances of returning to their preoperative functional state.

PMID- 15961763
TI  - Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17
      demethoxygeldanamycin in patients with advanced malignancies.
AB  - PURPOSE: To study the toxicity and pharmacokinetic-pharmacodynamic profile of 17
      allylamino, 17- demethoxygeldanamycin (17-AAG) and to recommend a dose for phase
      II trials. PATIENTS AND METHODS: This was a phase I study examining a once-weekly
      dosing schedule of 17-AAG. Thirty patients with advanced malignancies were
      treated. RESULTS: The highest dose level reached was 450 mg/m(2)/week. The dose
      limiting toxicities (DLTs) encountered were grade 3 diarrhea in three patients
      (one at 320 mg/m(2)/week and two at 450 mg/m(2)/week) and grade 3 to 4
      hepatotoxicity (AST/ALT) in one patient at 450 mg/m(2)/week. Two of nine DLTs
      were at the highest dose level. Two patients with metastatic melanoma had stable
      disease and were treated for 15 and 41 months, respectively. The dose versus area
      under the curve-relationship for 17-AAG was linear (r(2) = .71) over the dose
      range 10 to 450 mg/m(2)/week, with peak plasma concentrations of 8,998 mug/L
      (standard deviation, 2,881) at the highest dose level. After the demonstration of
      pharmacodynamic changes in peripheral blood leukocytes, pre- and 24 hours post
      treatment, tumor biopsies were performed and demonstrated target inhibition (c
      RAF-1 inhibition in four of six patients, CDK4 depletion in eight of nine
      patients and HSP70 induction in eight of nine patients) at the dose levels 320
      and 450 mg/m(2)/week. It was not possible to reproducibly demonstrate these
      changes in biopsies taken 5 days after treatment. CONCLUSION: It has been
      possible to demonstrate that 17-AAG exhibits a tolerable toxicity profile with
      therapeutic plasma concentrations and target inhibition for 24 hours after
      treatment and some indications of clinical activity at the dose level 450
      mg/m(2)/week. We recommend this dose for phase II clinical trials.

PMID- 15961765
TI  - Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant
      epirubicin for early breast cancer: correlation with doses of epirubicin and
      cyclophosphamide.
AB  - PURPOSE: We reviewed follow-up of patients treated in 19 randomized trials of
      adjuvant epirubicin in early breast cancer to determine incidence, risk, and risk
      factors for subsequent acute myeloid leukemia (AML) and myelodysplastic syndrome
      (MDS). PATIENTS AND METHODS: The patients (N = 9,796) were observed from the
      start of adjuvant treatment (53,080 patient-years). Cases of AML or MDS (AML/MDS)
      were reported, with disease characteristics. Incidence and cumulative risk were
      compared for possible risk factors, for assigned regimens, and for administered
      cumulative doses of epirubicin and cyclophosphamide. RESULTS: In 7,110 patients
      treated with epirubicin-containing regimens (92% of whom also received
      cyclophosphamide), 8-year cumulative probability of AML/MDS was 0.55% (95% CI,
      0.33% to 0.78%). The risk of developing AML/MDS increased in relation to planned
      epirubicin dose per cycle, planned epirubicin dose-intensity, and administered
      cumulative doses of epirubicin and cyclophosphamide. Patients with administered
      cumulative doses of both epirubicin and cyclophosphamide not exceeding those used
      in standard regimens (</= 720 mg/m(2) and </= 6,300 mg/m(2), respectively) had an
      8-year cumulative probability of developing AML/MDS of 0.37% (95% CI, 0.13% to
      0.61%) compared with 4.97% (95% CI, 2.06% to 7.87%) for patients administered
      higher cumulative doses of both epirubicin and cyclophosphamide. CONCLUSION:
      Patients treated with standard cumulative doses of adjuvant epirubicin (</= 720
      mg/m(2)) and cyclophosphamide (</= 6,300 mg/m(2)) for early breast cancer have a
      lower probability of secondary leukemia than patients treated with higher
      cumulative doses. Increased risk of secondary leukemia must be considered when
      assessing the potential benefit to risk ratio of higher than standard doses.

PMID- 15961764
TI  - Randomized phase II/III trial of interferon Alfa-2a with and without 13-cis
      retinoic acid in patients with progressive metastatic renal cell Carcinoma: the
      European Organisation for Research and Treatment of Cancer Genito-Urinary Tract
      Cancer Group (EORTC 30951).
AB  - PURPOSE: A randomized phase II/III trial was conducted to determine whether
      combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a
      (IFN-alpha-2a) was superior to IFN-alpha-2a alone in patients with progressive
      metastatic renal cell carcinoma. PATIENTS AND METHODS: Three hundred twenty
      patients were randomly assigned to treatment with IFN-alpha-2a plus 13-CRA or to
      IFN-alpha-2a alone. IFN-alpha-2a was given daily subcutaneously, starting at a
      dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU
      by increments of 3 MU. Patients randomly assigned to combination therapy received
      oral 13-CRA 1 mg/kg/d plus IFN-alpha-2a. RESULTS: Median time to progression was
      5.1 months for patients treated with the combination and 3.4 months for patients
      on IFN-alpha-2a alone (P = .008). Progression-free survival rates at 6 months
      were 43% for patients receiving combined therapy and 30% for patients on IFN
      alpha-2a, and at 12 months, 27% and 17%, respectively. Median overall survival
      was 17.3 months for patients on IFN-alpha-2a and 13-CRA, and 13.2 months for
      patients treated with IFN-alpha-2a (P = .048). Twenty-two percent of the patients
      receiving the combination stopped treatment due to toxicity, as compared with 16%
      on IFN-alpha-2a. CONCLUSION: Progression-free and overall survival for patients
      with progressive metastatic renal cell carcinoma treated with IFN-alpha-2a plus
      13-CRA were significantly longer compared with patients on IFN-alpha-2a alone (P
      = .007 and P = .048, respectively). Improvement in efficacy in the combination
      arm was accompanied by increased, though not serious, toxicity.

PMID- 15961766
TI  - Chemotherapy for breast cancer during pregnancy: an 18-year experience from five
      London teaching hospitals.
AB  - PURPOSE: The rare association between breast cancer and pregnancy means that few
      oncologists gain an expertise in this area. In particular, there are few
      published data concerning the use of chemotherapy for breast cancer during
      pregnancy. In this retrospective case series, we describe the experiences of five
      hospitals in London, United Kingdom, and how they manage this condition. PATIENTS
      AND METHODS: Retrospective searches were performed at five London hospitals in
      order to identify women who received chemotherapy for breast cancer while
      pregnant. RESULTS: Twenty-eight women were identified who had received
      chemotherapy for breast cancer during pregnancy. Twenty-four women received
      adjuvant or neoadjuvant chemotherapy for early breast cancer, and four women
      received palliative chemotherapy for metastatic disease. A total of 116 cycles of
      chemotherapy were administered during pregnancy. Sixteen women were treated with
      anthracycline-based chemotherapy and 12 received cyclophosphamide, methotrexate,
      and fluorouracil. All but one of the women were treated after the first
      trimester. One spontaneous abortion occurred in the woman treated during her
      first trimester; otherwise, there were no serious adverse consequences for the
      mothers or neonates. CONCLUSION: These data provide evidence that in terms of
      peripartum complications and immediate fetal outcome, chemotherapy can be safely
      administered to women during the second and third trimesters of pregnancy.

PMID- 15961767
TI  - Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta
      analysis of randomized controlled trials.
AB  - PURPOSE: Current treatment for febrile neutropenia (FN) includes hospitalization
      for evaluation, empiric broad-spectrum antibiotics, and other supportive care.
      Clinical trials have reported conflicting results when studying whether the
      colony-stimulating factors (CSFs) improve outcomes in patients with FN. This
      Cochrane Collaboration review was undertaken to further evaluate the safety and
      efficacy of the CSFs in patients with FN. METHODS: An exhaustive literature
      search was undertaken including major electronic databases (CANCERLIT, EMBASE,
      LILACS, MEDLINE, SCI, and the Cochrane Controlled Trials Register). All
      randomized controlled trials that compare CSFs plus antibiotics versus
      antibiotics alone for the treatment of established FN in adults and children were
      sought. A meta-analysis of the selected studies was performed. RESULTS: More than
      8,000 references were screened, with 13 studies meeting eligibility criteria for
      inclusion. The overall mortality was not influenced significantly by the use of
      CSF (odds ratio [OR] = 0.68; 95% CI, 0.43 to 1.08; P = .1). A marginally
      significant result was obtained for the use of CSF in reducing infection-related
      mortality (OR = 0.51; 95% CI, 0.26 to 1.00; P = .05). Patients treated with CSFs
      had a shorter length of hospitalization (hazard ratio [HR] = 0.63; 95% CI, 0.49
      to 0.82; P = .0006) and a shorter time to neutrophil recovery (HR = 0.32; 95% CI,
      0.23 to 0.46; P < .00001). CONCLUSION: The use of the CSFs in patients with
      established FN caused by cancer chemotherapy reduces the amount of time spent in
      hospital and the neutrophil recovery period. The possible influence of the CSFs
      on infection-related mortality requires further investigation.

PMID- 15961768
TI  - Cyclin D1 in breast cancer pathogenesis.
AB  - Taking a perspective on available evidence that emphasizes relevance to human
      disease, cyclin D1 is solidly established as an oncogene with an important
      pathogenetic role in breast cancer and other human tumors. However, the precise
      cellular mechanisms through which aberrant cyclin D1 expression drives human
      neoplasia are less well established. Indeed, emerging evidence suggests that
      cyclin D1 might act, predominantly or at least in part, through pathways that do
      not involve its widely accepted function as a cell cycle regulator. Although
      therapeutic exploitation of the role of cyclin D1 as a molecular driver of breast
      cancer carries great promise, it is also suggested that direct targeting of the
      cyclin D1 gene or gene products may prove more successful than approaches that
      rely on arguably incomplete knowledge of the oncogenic mechanisms of cyclin D1.

PMID- 15961769
TI  - CNS manifestations of malignancies: case 1. Conjunctival relapse of acute
      lymphoblastic leukemia heralding pituitary and CNS disease.

PMID- 15961770
TI  - CNS manifestations of malignancies: case 2. Skull and brain metastasis from
      tibial osteosarcoma.

PMID- 15961771
TI  - CNS manifestations of malignancies: case 3. Leukemic optic neuropathy
      complicating leukemia cutis.

PMID- 15961772
TI  - Unrealistic expectations.

PMID- 15961774
TI  - How lymphotoxic is dose-intensified temozolomide? The glioblastoma experience.

PMID- 15961776
TI  - Weekly epirubicin plus tamoxifen versus tamoxifen alone as adjuvant treatment of
      operable, node-positive, elderly breast cancer patients.

PMID- 15961777
TI  - Fellows' forum forgotten?

PMID- 15961779
TI  - Radiation therapy and tamoxifen: concurrent or sequential? It's no longer the
      question!

PMID- 15961781
TI  - Potential risk of a common hereditary thrombophilia and adjuvant chemotherapy for
      low-stage breast cancer.

PMID- 15961782
TI  - Cognitive impairment, aromatase inhibitors, and age.

PMID- 15961783
TI  - Clinical responses to gefinitib after failure of treatment with cetuximab in
      advanced non-small-cell lung cancer.

PMID- 15961784
TI  - Thematic review series: the immune system and atherogenesis. Molecular mechanisms
      regulating monocyte recruitment in atherosclerosis.
AB  - Cardiovascular disease, a progressive disorder characterized by the accumulation
      of lipids in the artery wall, is a leading cause of death in Western societies.
      One of the initial events in atherogenesis involves the recruitment of
      inflammatory cells from the circulation into the developing lesion. Studies
      during the past decade have underscored the role of inflammatory mediators in
      disease initiation and progression. Critical progress has been made in our
      understanding of the complex mechanisms by which monocytes, macrophages, and T
      cells accumulate in atherosclerotic plaques. Experimental research has identified
      several candidate adhesion proteins and chemokines that are critically involved
      in the recruitment process, and encouraging data provide a mechanistic framework
      for new therapeutic targets. This review provides an overview of our current
      understanding of the mechanisms that direct the recruitment of monocytes to, and
      their retention in, atherosclerotic lesions.

PMID- 15961785
TI  - Free fatty acid release from human breast cancer tissue inhibits cytotoxic T
      lymphocyte-mediated killing.
AB  - Immune-mediated antitumor activities confront a variety of tumor-mediated defense
      mechanisms. Here, we describe a new mechanism involving FFA that may allow breast
      cancer to evade immune clearance. We determined the IC50 at which unbound free
      fatty acids (FFA(u)) inhibit murine cytotoxic T-lymphocyte (CTL)-mediated killing
      to assess the physiologic relevance of this phenomenon. We found that the IC50
      for unbound oleate is 125 +/- 30 nM, approximately 200-fold greater than normal
      plasma levels. FFA inhibition, however, may play an important role in breast
      cancer because we found that large quantities of FFAs are released constitutively
      into the media surrounding samples of human breast cancer but not normal or
      benign tissue. FFA(u) concentration ([FFA(u)]) increased to at least 25 nM in 20
      of 22 cancer tissue samples and exceeded 100 nM in 11 patients. Media from these
      samples inhibited CTL-mediated killing. Extrapolation from our in vitro
      conditions suggests that for tumor interstitial fluid, in vivo [FFA(u)] may be
      300-fold greater than we observed in vitro. Although breast cancer release of FFA
      may suppress effector cell antitumor activity, strategies that reduce
      interstitial [FFA(u)] may significantly improve antitumor immune therapies.

PMID- 15961786
TI  - On the importance of anandamide structural features for its interactions with
      DPPC bilayers: effects on PLA2 activity.
AB  - The acylethanolamide anandamide (AEA) occurs in a variety of mammalian tissues
      and, as a result of its action on cannabinoid receptors, exhibits several
      cannabimimetic activities. Moreover, some of its effects are mediated through
      interaction with an ion channel-type vanilloid receptor. However, the chemical
      features of AEA suggest that some of its biological effects could be related to
      physical interactions with the lipidic part of the membrane. The present work
      studies the effect of AEA-induced structural modifications of the
      dipalmitoylphosphatidylcholine (DPPC) bilayer on phospholipase A2 (PLA2)
      activity, which is strictly dependent on lipid bilayer features. This study,
      performed by 2-dimethylamino-(6-lauroyl)-naphthalene fluorescence, demonstrates
      that the effect of AEA on PLA2 activity is concentration-dependent. In fact, at
      low AEA/DPPC molar ratios (from R = 0.001 to R = 0.04), there is an increase of
      the enzymatic activity, which is completely inhibited for R = 0.1. X-ray
      diffraction data indicate that the AEA affects DPPC membrane structural
      properties in a concentration-dependent manner. Because the biphasic effect of
      increasing AEA concentrations on PLA2 activity is related to the induced
      modifications of membrane bilayer structural properties, we suggest that AEA
      phospholipid interactions may be important to produce, at least in part, some of
      the similarly biphasic responses of some physiological activities to increasing
      concentrations of AEA.

PMID- 15961787
TI  - Acid sphingomyelinase is induced by butyrate but does not initiate the anticancer
      effect of butyrate in HT29 and HepG2 cells.
AB  - Butyric acid and sphingomyelin (SM) affect colonic tumorigenesis. We examined the
      potential link between butyrate stimulation and SM metabolism in colonic and
      hepatic cancer cell lines. After incubating HT29 and HepG2 cells with butyrate
      and other short-chain fatty acids, we found that butyrate increased acid but not
      neutral or alkaline sphingomyelinase (SMase) activity by 10- to 20-fold. The
      effects occurred after 16 h of incubation and were associated with reduced SM and
      phosphatidylcholine contents and increased ceramide levels. Northern blotting
      showed increased acid SMase mRNA levels in these cells after butyrate
      stimulation. Propionate was less potent, and acetate had no effect. No similar
      changes of acid phosphatase could be identified. At concentrations that increased
      acid SMase expression, butyrate inhibited cell proliferation, activated caspase
      3, and induced apoptosis. However, the antiproliferative and apoptotic effects of
      butyrate preceded the changes of acid SMase and were not affected by knocking
      down acid SMase expression by small, interfering RNA. In addition, butyrate
      induced acid SMase expression was not affected by blocking the caspase pathway.
      In conclusion, butyrate regulates SM metabolism by stimulating acid SMase
      expression in colon and liver cancer cells, but the increased acid SMase is not a
      critical mechanism for initiating the anticancer effects of butyrate.

PMID- 15961788
TI  - Human hormone-sensitive lipase (HSL): expression in white fat corrects the white
      adipose phenotype of HSL-deficient mice.
AB  - In white adipose tissue (WAT), hormone-sensitive lipase (HSL) can mediate
      lipolysis, a central pathway in obesity and diabetes. Gene-targeted HSL-deficient
      (HSL-/-) mice with no detectable HSL peptide or activity (measured as cholesteryl
      esterase) have WAT abnormalities, including low mass, marked heterogeneity of
      cell diameter, increased diacylglycerol content, and low beta-adrenergic
      stimulation of adipocyte lipolysis. Three transgenic mouse strains preferentially
      expressing human HSL in WAT were bred to a HSL-/- background. One, HSL-/- N,
      expresses normal human HSL (41.3 +/- 9.1% of normal activity); two express a
      serine-to-alanine mutant (S554A) initially hypothesized to be constitutively
      active: HSL-/- ML, 50.3 +/- 12.3% of normal, and HSL-/- MH, 69.8 +/- 15.8% of
      normal. In WAT, HSL-/- N mice resembled HSL+/+ controls in WAT mass, histology,
      diacylglyceride content, and lipolytic response to beta-adrenergic agents. In
      contrast, HSL-/- ML and HSL-/- MH mice resembled nontransgenic HSL-/- mice,
      except that diacylglycerol content and perirenal and inguinal WAT masses
      approached normal in HSL-/- MH mice. Therefore, 1) WAT expression of normal human
      HSL markedly improves HSL-/- WAT biochemically, physiologically, and
      morphologically; 2) similar levels of S554A HSL have a low physiological effect
      despite being active in vitro; and 3) diacylglycerol accumulation is not
      essential for the development of the characteristic WAT pathology of HSL-/- mice.

PMID- 15961789
TI  - Higher order lipase gene association with plasma triglycerides.
AB  - Lipoprotein lipase, HL, and endothelial lipase (EL) are proteoglycan-bound
      enzymes that regulate plasma lipoprotein levels through coordinated triglyceride
      (TG) lipase and phospholipase activity. We hypothesized that single nucleotide
      polymorphisms (SNPs) in lipase genes would have higher order impact on plasma
      lipoproteins beyond the influence of individual SNPs. In a sample of asymptomatic
      Caucasian subjects (n = 738), we used a two-stage approach, first identifying
      groups of subjects with similar multilocus lipase genotypes and then
      characterizing the relationships between genotype groups and plasma lipids. Using
      complementary methods, including a permutation test procedure and a mixed-effects
      modeling approach, we found a higher order interaction between four SNPs in three
      lipase genes (EL 2,237 3' untranslated region, EL Thr111Ile, HL -514C/T, and LPL
      HindIII) and plasma TG levels. Subjects who were heterozygous for all four lipase
      SNPs had significantly higher plasma TG levels beyond the effect of individual
      lipase SNPs and environmental factors, even after correcting for multiple
      comparisons. In conclusion, lipase genes had synergistic association with plasma
      TG beyond individual gene effects. Higher order multilocus genotype contributions
      to dyslipidemia and atherosclerotic cardiovascular disease need to be considered
      a priori because they may have an important effect even in the absence of
      significant main effects of the individual genes.

PMID- 15961790
TI  - Control of ACAT2 liver expression by HNF1.
AB  - ACAT catalyzes the formation of cholesteryl esters from cholesterol and long
      chain fatty acids. There are two known genes encoding the two ACAT enzymes, ACAT1
      and ACAT2 (also known as Soat1 and Soat2). In adult humans, ACAT1 is present in
      most tissues, whereas ACAT2 is localized to enterocytes and hepatocytes. In this
      report, we elucidate the mechanisms that control the liver-specific expression of
      the human ACAT2 gene. We identified hepatic nuclear factor 1 (HNF1) as an
      important liver-specific trans-acting element for the human ACAT2 gene using the
      human hepatocellular carcinoma cell lines HuH7 and HepG2. Targeted deletion of
      the HNF1 binding site in the DNA sequence abolished not only the basal promoter
      function in HepG2 and HuH7 cells but also the induction of the ACAT2 promoter by
      HNF1. Electrophoretic mobility shift assay and chromatin immunoprecipitation
      assay demonstrated that the transcription factors HNF1alpha and HNF1beta interact
      with this region in the human ACAT2 gene in vitro and in vivo. These data
      indicate that a) the identified HNF1 binding site serves as a positive regulator
      sequence, b) the binding site is functionally active both in vivo and in vitro,
      and c) the transcription factors HNF1alpha and HNF1beta, which bind to this site,
      play an important part in the regulation of the human ACAT2 promoter.

PMID- 15961791
TI  - A sandwich enzyme-linked immunosorbent assay for human plasma apolipoprotein A-V
      concentration.
AB  - Apolipoprotein A-V (apoA-V) is a recently discovered apolipoprotein that appears
      to have a role in plasma triglyceride (TG) transport. We have developed an ELISA
      for apoA-V using monoclonal antibodies that has a lower limit of detection of 0.3
      ng/ml and linearity up to 20 ng/ml. The ELISA was then used to quantify plasma
      apoA-V in 196 healthy subjects and 106 patients with insulin-resistant diabetes
      mellitus. In the healthy subjects, total apoA-V concentration was 179.2 +/- 74.8
      ng/ml, and it was greater in females than in males (P < 0.005). It was correlated
      positively with the plasma HDL cholesterol (r = 0.32, P < 0.0001), apoA-I (r =
      0.27, P = 0.0001), and apoE (r = 0.18, P = 0.011) concentrations and negatively
      with plasma TG concentration (r = -0.22, P = 0.021). In relation to single
      nucleotide polymorphism 3 (-1131C/T) of the apoA-V gene, apoA-V concentration was
      higher in the T/T type than in the C/C type (P < 0.01). Plasma TG concentration
      was lower in the T/T type than in the C/C or C/T type (P < 0.05). ApoA-V
      concentration was lower in the diabetic patients (69.4 +/- 44.3 ng/ml; P < 0.01)
      than in the healthy controls.

PMID- 15961792
TI  - Growth charts for babies.

PMID- 15961793
TI  - Strontium ranelate for the treatment of osteoporosis.

PMID- 15961794
TI  - Reducing variation in surgical care.

PMID- 15961795
TI  - Buruli ulcer.

PMID- 15961796
TI  - Junior doctors' shifts and sleep deprivation.

PMID- 15961797
TI  - Italians fail to overturn restrictive reproduction law.

PMID- 15961799
TI  - Article removed after US complains it could help terrorists.

PMID- 15961801
TI  - G8 cancels debt of the world's poorest countries.

PMID- 15961803
TI  - US Supreme Court says no to medical marijuana.

PMID- 15961805
TI  - Mental health should have same priority as physical health.

PMID- 15961806
TI  - Canadian Supreme Court upholds right to take out private health insurance.

PMID- 15961807
TI  - Appeal launched to step up research and development for neglected diseases.

PMID- 15961808
TI  - HIV infections in the US pass one million.

PMID- 15961810
TI  - More information needed on risks of over the counter drugs.

PMID- 15961811
TI  - Living near a nuclear power station doesn't increase a child's cancer risk.

PMID- 15961812
TI  - Debt ridden trust has no cash to pay creditors.

PMID- 15961813
TI  - Drug regulator criticised for error in reporting consultation results.

PMID- 15961814
TI  - Outcomes of planned home births with certified professional midwives: large
      prospective study in North America.
AB  - OBJECTIVE: To evaluate the safety of home births in North America involving
      direct entry midwives, in jurisdictions where the practice is not well integrated
      into the healthcare system. DESIGN: Prospective cohort study. SETTING: All home
      births involving certified professional midwives across the United States (98% of
      cohort) and Canada, 2000. PARTICIPANTS: All 5418 women expecting to deliver in
      2000 supported by midwives with a common certification and who planned to deliver
      at home when labour began. MAIN OUTCOME MEASURES: Intrapartum and neonatal
      mortality, perinatal transfer to hospital care, medical intervention during
      labour, breast feeding, and maternal satisfaction. RESULTS: 655 (12.1%) women who
      intended to deliver at home when labour began were transferred to hospital.
      Medical intervention rates included epidural (4.7%), episiotomy (2.1%), forceps
      (1.0%), vacuum extraction (0.6%), and caesarean section (3.7%); these rates were
      substantially lower than for low risk US women having hospital births. The
      intrapartum and neonatal mortality among women considered at low risk at start of
      labour, excluding deaths concerning life threatening congenital anomalies, was
      1.7 deaths per 1000 planned home births, similar to risks in other studies of low
      risk home and hospital births in North America. No mothers died. No discrepancies
      were found for perinatal outcomes independently validated. CONCLUSIONS: Planned
      home birth for low risk women in North America using certified professional
      midwives was associated with lower rates of medical intervention but similar
      intrapartum and neonatal mortality to that of low risk hospital births in the
      United States.

PMID- 15961815
TI  - Creative use of existing clinical and health outcomes data to assess NHS
      performance in England: Part 1--performance indicators closely linked to clinical
      care.

PMID- 15961816
TI  - Basic transthoracic echocardiography.

PMID- 15961817
TI  - ABC of conflict and disaster: military approach to medical planning in
      humanitarian operations.

PMID- 15961818
TI  - Aspirin for everyone older than 50? For.

PMID- 15961819
TI  - Aspirin for everyone older than 50? Against.

PMID- 15961820
TI  - Obstacles to maintaining licensure in the United States.

PMID- 15961821
TI  - The General Medical Council and the future of revalidation: GMC prepares to
      deliver notable improvements.

PMID- 15961822
TI  - The General Medical Council and the future of revalidation: revalidation,
      discretionary points, clinical excellence awards--steps on the same ladder.

PMID- 15961823
TI  - The General Medical Council and the future of revalidation: GMC member responds.

PMID- 15961824
TI  - Underwater birth and neonatal respiratory distress: case report does not
      constitute reliable evidence.

PMID- 15961825
TI  - The General Medical Council and the future of revalidation: revalidation process
      would not pass appraisal.

PMID- 15961826
TI  - The General Medical Council and the future of revalidation: profession needs to
      debate regulator's role.

PMID- 15961827
TI  - The General Medical Council and the future of revalidation: regulation,
      regulation, regulation.

PMID- 15961828
TI  - Was Rodney Ledward a statistical outlier? Statistical method may be difficult to
      apply in clinical practice.

PMID- 15961829
TI  - Was Rodney Ledward a statistical outlier? Initial investigations of outliers must
      be chosen carefully.

PMID- 15961830
TI  - Some patients stop treatment when variables improve.

PMID- 15961831
TI  - Treatment of postmenopausal osteoporosis: exercise was not mentioned.

PMID- 15961832
TI  - Was Rodney Ledward a statistical outlier? Ledward's managers knew for 10 years
      that he was a risk.

PMID- 15961833
TI  - The tide of prescribing for depression is turning.

PMID- 15961834
TI  - SARS changed medical dress code.

PMID- 15961835
TI  - Incomprehensible consent forms: child friendly consent forms lead the way.

PMID- 15961836
TI  - Incomprehensible consent forms: plain English is important.

PMID- 15961837
TI  - Are you sitting comfortably?

PMID- 15961838
TI  - Ergonomics of digital imaging.
AB  - There has been an increase in the use of digital imaging in recent years and
      radiologists have almost universally accepted the use of computers in their day
      to-day work. Completely filmless radiology departments, with all reporting being
      done on visual display terminals and picture archiving and communications systems
      (PACS) around the department, are already a reality in many places in the UK and
      other parts of the world. There is a constant need of computers for literature
      searches on the web, e-mails, communication and preparing lectures and
      presentations. With this explosive increase in the use of computers in the
      hospital, it is imperative that the use of computer monitor screens for medical
      use is optimized in order to avoid eyestrain and fatigue. This is especially
      important as tired eyes and brains may be more likely to commit errors. We have
      reviewed the current literature to elaborate a few useful measures that can be
      taken to minimize the effect of excessive computer use in a soft-copy radiology
      reporting area on the eyes and the musculoskeletal system. We recommend that
      optimal placement of computer monitors with user-friendly PACS terminal
      interfaces will ensure greater acceptability and improve reporting efficiency and
      accuracy. Good work practices to ensure reduction of reporting errors are
      highlighted.

PMID- 15961839
TI  - 3D reconstruction of the skeletal anatomy of the normal neonatal foot using 3D
      ultrasound.
AB  - Currently imaging plays a limited role in the assessment of the neonate with a
      foot deformity. The aim of this study was to establish a technique for examining
      the neonatal foot with three-dimensional ultrasound (3D US). 3D US was attempted
      on the normal feet of 20 infants (9 male, 11 female) under 6 weeks old (range 35
      41 days). The data sets were obtained whilst the infants were feeding or asleep
      to minimize movement artefact. A high-resolution optically tracked freehand 3D US
      system (Diasus, 16 MHz transducer) was used with Stradx software to acquire and
      analyse the data sets. Manual segmentation of the non-ossified tarsi from the
      data sets was performed. Five infants were too restless to be examined. 107 data
      sets were recorded from 22 feet of the remaining 15 infants. 21 of the data sets
      were discarded due to movement artefact. 86 were suitable for manual
      segmentation. Surface interpolation of the segmented data sets produced surface
      rendered reconstructions illustrating the complex 3D anatomy of the foot. This
      new technique may offer a method of examining the deformed foot, e.g. congenital
      talipes equinovarus.

PMID- 15961840
TI  - Incidence of upper limb venous thrombosis associated with peripherally inserted
      central catheters (PICC).
AB  - The objective of this study was to prospectively determine the incidence of
      venous thrombosis (VT) in the upper limbs in patients with peripherally inserted
      central catheters (PICC). We prospectively investigated the incidence of VT in
      the upper limbs of 26 patients who had PICC inserted. The inclusion criteria were
      all patients who had a PICC inserted, whilst the exclusion criterion was the
      inability to perform a venogram (allergies, previous contrast medium reaction and
      inability of gaining venous access). Both valved and non-valved catheters were
      evaluated. Prior to removal of the PICC, an upper limb venogram was performed.
      The number of segments involved with VT were determined. The duration of central
      venous catheterization was classified as; less than 6 days, between 6 days and 14
      days and more than 14 days. VT was confirmed in 38.5% (10/26) of the patients.
      The majority 85.7% (12/14) were complete occlusive thrombi and the majority of VT
      only involved one segment. There was no statistical correlation between the site
      of insertion of the PICC and the location of VT. Neither was there any observed
      correlation between the occurrence of VT with the patient's history of
      hypertension, hypercholesterolaemia, coronary artery disease, diabetes mellitus,
      cardiac insufficiency, smoking or cancer. There was also no statistical
      correlation with the size of the catheter. In conclusion, PICCs are associated
      with a significant risk of upper extremity deep vein thrombosis (UEVT).

PMID- 15961841
TI  - Protein C and/or S deficiency presenting as peripheral arterial insufficiency.
AB  - Although protein C and/or S deficiency has frequently been associated with venous
      thromboembolic events, instances of arterial thromboses have been reported.
      However, the exact incidence of protein C and/or S deficiency in patients with
      peripheral arterial insufficiency has not been established. Furthermore, given
      the lack of adequate studies to define the natural history and angiographic
      findings of these patients, the treatment has not been well delineated.
      Therefore, we conducted a prospective study to investigate the prevalence,
      characteristic angiographic findings and optimal treatments in patients with
      peripheral arterial insufficiency associated with protein C and/or S deficiency.
      Between September 2000 and August 2004, 133 patients who presented with
      peripheral arterial insufficiency underwent hypercoagulability tests before the
      initiation of any treatments. Of these, 11 patients (8.3%) with protein C and/or
      S deficiency were included in this study. There were nine males and two females.
      The ages ranged from 38 years to 72 years (mean 57 years). All patients showed
      characteristic angiographic findings: long segment thrombotic occlusion of a main
      peripheral artery without evidence of atherosclerosis or with mild
      atherosclerotic changes in the aorta and other major arterial trees. Surgical or
      endovascular procedures were performed in nine patients: bypass graft in four,
      thrombectomy in four and catheter-directed thrombolysis in one. Conservative
      treatment with full anticoagulation was performed in two patients. All patients
      received pre- and post-operative anticoagulation. Except for one amputated case,
      clinical and vascular laboratory improvements were achieved in 10 patients. Mean
      follow-up period was 21 months (range 4-45 months). However, one patient, in whom
      re-vascularization surgery was performed successfully, discontinued warfarin
      therapy himself at 10 months after surgery, graft occlusion and limb loss
      occurred at 30 months after surgery. This initial experience suggests that
      protein C and/or S deficiency may be an independent risk factor for peripheral
      arterial insufficiency. Patients who present with peripheral arterial
      insufficiency and protein C and/or S deficiency demonstrate characteristic
      angiographic findings. Once the diagnosis of protein C and/or S deficiency is
      made, patients should be treated with life-long anticoagulation.

PMID- 15961842
TI  - Emergency management and infection control in a radiology department during an
      outbreak of severe acute respiratory syndrome.
AB  - The World Health Organization classified Taiwan as a serious epidemic-stricken
      area when the extent of severe acute respiratory syndrome (SARS) in Taiwan became
      clear. As of 11 July 2003, 671 probable SARS cases had been identified in Taiwan
      and 7 healthcare workers had died from the disease. Radiographers were easily
      infected by SARS because they had close contact with suspected or probable cases
      while conducting chest X-ray examinations. Three radiographers had been infected
      by the end of May 2003. Because of the impact of SARS on the Radiology
      Department, the department established a SARS emergency infection control team
      and re-designed the department's infection-control and emergency-management
      procedures based on the concept of risk-grade protection. This effort included
      installing a radiographic room at the fever-screening station, re-allocating
      human resources in the Radiology Department, training the department staff in
      infection control, and drafting new operational procedures for radiographers
      conducting X-ray examinations on SARS patients. The goal of this program was to
      reduce the infection rate and distribute materials efficiently in the department.
      This article introduces the emergency-management procedure of the Radiology
      Department during the SARS outbreak and the infection-protection experience of
      the department staff.

PMID- 15961843
TI  - Modelling of output factors for conformal megavoltage X-ray beams.
AB  - A method is described for calculating the output from conformally shaped
      megavoltage X-ray beams. The model has been developed for Varian accelerators but
      is shown to work for accelerators from another manufacturer. The use of dynamic
      wedging and both static and dynamic multileaf collimated beams are included in
      the model. For any linear accelerator, the data required are a set of measured
      output factors for square beams, an in-air profile and a limited number of
      readily available parameters defining the geometry of the head of the
      accelerator. The three components of the output, namely primary, head scatter and
      phantom scatter are modelled and calculated individually for any point in a beam.
      An optimization procedure is developed that automatically determines the eight
      parameters required to model an accelerator in order for these calculations to be
      performed. The performance of the method is demonstrated for shaped beams using
      asymmetric and multileaf collimation, both with and without wedging, and for a
      range of beam energies. The model has been incorporated into a computer program
      that is used clinically.

PMID- 15961844
TI  - The dose response of normoxic polymer gel dosimeters measured using X-ray CT.
AB  - X-ray CT was used to determine the dose response of normoxic polymer gel
      dosimeters. Normoxic polymer gel dosimeters were manufactured and irradiated up
      to 150 Gy. Up to 50 CT images were acquired on a Toshiba Aquilion Multislice CT
      scanner using protocols for 80 kV and 135 kV to determine dose response. HU-dose
      sensitivity, the linear regression of data for the HU versus dose for the linear
      part of the curve up to 60 Gy was 0.38+/-0.07 HU Gy(-1) for 135 kV and 0.37+/
      0.01 HU Gy(-1) for 80 kV. Dose resolution was found to be < 1.3 Gy for an
      absorbed dose range up to 70 Gy for 135 kV, similar to that measured previously
      for polyacrylamide gel (PAG). Although the HU-dose sensitivity was lower than
      that previously measured for PAG gel dosimeters it had a greater range of
      absorbed dose indicating that normoxic polymer gel dosimeters have potential in
      CT gel dosimetry.

PMID- 15961845
TI  - Limited ARSAC licence acquisition for radionuclide radiology.
AB  - Radionuclide radiology faces a potentially crippling future manpower shortage. A
      combination of future retirement, few trainees and many currently unfilled posts
      threatens to limit future service delivery. The case is made for in-house modular
      training of existing consultants as the way forward for radionuclide radiology,
      allowing limited ARSAC licence acquisition. We propose this as a viable solution
      to the manpower problem in radionuclide radiology.

PMID- 15961846
TI  - The use of CT-MR image registration to define target volumes in pelvic
      radiotherapy in the presence of bilateral hip replacements.
AB  - Increasing numbers of patients with hip replacements are presenting for pelvic
      radiotherapy, which is usually planned using CT images. Image artefacts caused by
      the presence of metallic implants tend not to be severe for single hip
      replacements and allow for adequate definition of target volumes. When bilateral
      hip replacements are present, the image artefacts can render CT images useless
      for target definition, particularly for tumours of the prostate and bladder. MR
      images are not susceptible to such severe artefacts. This note describes a small
      series of patients with bilateral hip replacements on whom CT-MR image
      registration has been used to successfully define adequate target volumes.

PMID- 15961847
TI  - A local diagnostic reference level for velopharyngeal investigations.
AB  - The purpose of this study was to derive an initial local diagnostic reference
      level for velopharyngeal investigations carried out as standard radiological
      practice in the Medical Imaging Department, Queen Victoria Hospital, East
      Grinstead. This is a specialist video-fluoroscopic radiological technique used to
      evaluate velopharyngeal dysfunction, especially for paediatric patients. A
      retrospective analysis over a period of 7 months involving 50 examinations
      yielded dose-area product values ranging from 0.04 Gy cm(2) (minimum) to 0.37 Gy
      cm(2) (maximum) with a mean value of 0.11 Gy cm(2) and 3rd quartile value of 0.12
      Gy cm(2). The maximum effective dose was estimated as 0.016 mGy. An initial local
      diagnostic reference level of 0.12 Gy cm(2) has been levied.

PMID- 15961848
TI  - Pulmonary benign metastasising leiomyomas presenting as fluid-containing masses
      on CT in a patient with two unrelated malignancies.

PMID- 15961849
TI  - Basal cell adenoma of the parotid gland: dynamic CT and MRI findings.
AB  - Imaging findings in basal cell adenoma (BCA) of the parotid gland have been
      rarely reported. We report dynamic CT and MRI findings of BCA in the parotid
      gland in a 78-year-old woman. Dynamic CT study demonstrated strong multinodular
      contrast enhancement in the early phase which decreased gradually in the later
      phases. The mass was isointense on T(1) weighted and hyperintense on T(2)
      weighted MR images with a central haemorrhagic-necrotic component. The
      microscopic findings were consistent with membranous type BCA.

PMID- 15961850
TI  - Acute subdural haematoma without subarachnoid haemorrhage caused by rupture of an
      internal carotid artery bifurcation aneurysm: case report and review of
      literature.
AB  - Spontaneous pure acute subdural haematoma (ASDH) without intraparenchymal or
      subarachnoid haemorrhage caused by a ruptured cerebral aneurysm is extremely
      rare. To our knowledge, the present case is the first report of an internal
      carotid artery bifurcation aneurysm presenting as pure ASDH. Suitable diagnostic
      investigations and therapeutic strategies are discussed. Arterial origin of
      bleeding should be considered in all cases of non-traumatic ASDH and a vascular
      anomaly has to be excluded. The neurological status on admission dictates the
      appropriate timing and methodology of the neuroradiological investigations.

PMID- 15961851
TI  - CT and MRI appearances of inflammatory pseudotumour of the cervical lymph nodes.
AB  - Inflammatory pseudotumour (IPT), also known as plasma cell granuloma and
      inflammatory myofibroblastic tumour, is a rare cause of benign cervical
      lymphadenopathy which mimics malignant causes of cervical lymphadenopathy. The
      imaging features of IPT affecting the cervical lymph nodes have not previously
      been described. We present cross sectional imaging in a case of IPT occurring in
      a 42-year-old African-Caribbean man, from his initial presentation to a
      subsequent spontaneous reduction in the extent of lymphadenopathy.

PMID- 15961852
TI  - Anomalous pancreaticobiliary junction (APBJ) with the drainage of the uncinate
      process into the minor papilla: demonstration by MRI.
AB  - We report a case of a 30-year-old patient with anomalous pancreaticobiliary
      junction (APBJ) that has not been described before. The patient had a clinical
      history of recurrent attacks of pancreatitis, cholangitis and cholecystitis that
      were confirmed by abnormal laboratory values. Endoscopic retrograde
      cholangiopancreatography revealed a 20 mm long junction of choledoc and
      pancreatic duct, and uncinate process draining into the minor papilla. On MR
      cholangiopancreatography, strictures at the junction of hepatic duct, increased
      gallbladder wall thickness and intraductal stone in the pancreatic duct were
      demonstrated as complementary findings. Other MRI findings included decreased
      signal intensity of the pancreas consistent with fibrosis from past pancreatitis
      attacks and atrophy of the left liver lobe.

PMID- 15961853
TI  - Internal carotid artery dissection presenting with ipsilateral tenth and twelfth
      nerve palsies and apparent mass lesion on MRI.
AB  - We report the case of a 47-year-old man who presented with a few months' history
      of right-sided headache and dysphagia, with ipsilateral tenth and twelfth cranial
      nerve palsies on examination. The initial MRI showed an enhancing mass lesion in
      relation to the right carotid sheath and jugular foramen, and was reported as a
      possible paraganglioma. Subsequent angiography performed to assess tumour
      vascularity demonstrated a dissection involving a tonsillar loop of the right
      internal carotid artery (ICA). Imaging findings at MRI and angiography and the
      presentations and mechanisms of ICA dissection are briefly discussed.

PMID- 15961854
TI  - Radiological associations with dermatological disease.
AB  - Skin disease and its treatment may have radiological connotations. Though this
      article is not a comprehensive account of dermatological and radiological
      associations, it provides an eclectic selection of some common and some rare
      clinical entities, which the practicing radiologist may recognize or remember.

PMID- 15961855
TI  - BJR Review of the Year 2004.

PMID- 15961856
TI  - Simultaneously misleading acronyms in radiation therapy.

PMID- 15961858
TI  - Incidental finding on abdominal CT scan.

PMID- 15961859
TI  - Alteration of intracellular histamine H2 receptor cycling precedes antagonist
      induced upregulation.
AB  - Long-term administration of a histamine H2 receptor (H2R) antagonist (inverse
      agonist) induces upregulation of H2R in parietal cells, which may be relevant to
      the rebound hypersecretion of gastric acid that occurs after withdrawal of
      treatment. The mechanisms underlying this effect are unknown. We hypothesized
      that the H2R upregulation could be related to receptor trafficking and used H2R
      green fluorescent protein (H2R-GFP) to test the hypothesis. Human H2R-GFP was
      generated and functionally expressed in HEK-293 cells. Binding of the H2R
      antagonist [3H]tiotidine was performed to quantify H2R expression, and H2R-GFP
      was imaged in living cells by confocal and evanescent wave microscopy. The
      binding affinity of [3H]tiotidine was not significantly different between H2R-GFP
      and wild-type H2R-expressing HEK-293 cells, both of which had constitutive
      activity of adenylate cyclase. Visualization of H2R-GFP revealed that the agonist
      induced H2R internalization and the antagonist-induced recycling of the
      internalized H2R from the recycling endosome within 2 h. Long exposure to the
      antagonist increased GFP fluorescence in the plasma membrane and also induced
      upregulation of H2R-GFP estimated by the binding assay, whereas long exposure to
      the agonist enhanced degradative trafficking of H2R-GFP. We examined whether the
      upregulation reflected an increase in receptor synthesis. Treatment with
      antagonist did not augment H2R mRNA, and subsequent inhibition of protein
      synthesis by cycloheximide had no effect on H2R upregulation. These findings
      suggested that upon exposure to an antagonist (inverse agonist), the equilibrium
      between receptor endocytosis and recycling is altered before H2R upregulation,
      probably via suppressing H2R degradation.

PMID- 15961860
TI  - L-type amino acids stimulate gastric acid secretion by activation of the calcium
      sensing receptor in parietal cells.
AB  - Parietal cells are the primary acid secretory cells of the stomach. We have
      previously shown that activation of the calcium-sensing receptor (CaSR) by
      divalent (Ca(2+)) or trivalent (Gd(3+)) ions stimulates acid production in the
      absence of secretagogues by increasing H(+),K(+)-ATPase activity. When
      overexpressed in HEK-293 cells, the CaSR can be allosterically activated by L
      amino acids in the presence of physiological concentrations of extracellular
      Ca(2+) (Ca(o)(2+); 1.5-2.5 mM). To determine whether the endogenously expressed
      parietal cell CaSR is allosterically activated by L-amino acids, we examined the
      effect of the amino acids L-phenylalanine (L-Phe), L-tryptophan, and L-leucine on
      acid secretion. In ex vivo whole stomach preparations, exposure to L-Phe resulted
      in gastric luminal pH significantly lower than controls. Studies using D-Phe
      (inactive isomer) failed to elicit a response on gastric pH. H(+)-K(+)-ATPase
      activity was monitored by measuring the intracellular pH (pH(i)) of individual
      parietal cells in isolated rat gastric glands and calculating the rate of H(+)
      extrusion. We demonstrated that increasing Ca(o)(2+) in the absence of
      secretagogues caused a dose-dependent increase in H(+) extrusion. These effects
      were amplified by the addition of amino acids at various Ca(o)(2+)
      concentrations. Blocking the histamine-2 receptor with cimetidine or inhibiting
      system L-amino acid transport with 2-amino-2-norbornane-carboxylic acid did not
      affect the rate of H(+) extrusion in the presence of L-Phe. These data support
      the conclusion that amino acids, in conjunction with a physiological Ca(o)(2+)
      concentration, can induce acid secretion independent of hormonal stimulation via
      allosteric activation of the stomach CaSR.

PMID- 15961862
TI  - "EEG happy families": the fun way to learn about common EEG abnormalities.

PMID- 15961863
TI  - The clinical role of evoked potentials.

PMID- 15961864
TI  - EEG in the diagnosis, classification, and management of patients with epilepsy.

PMID- 15961865
TI  - Nerve conduction studies: essentials and pitfalls in practice.

PMID- 15961866
TI  - The basics of electromyography.

PMID- 15961867
TI  - Specialised electromyography and nerve conduction studies.

PMID- 15961868
TI  - How to get the most out of nerve conduction studies and electromyography.

PMID- 15961870
TI  - EEG in neurological conditions other than epilepsy: when does it help, what does
      it add?

PMID- 15961871
TI  - The paid/unpaid work of participants.

PMID- 15961872
TI  - From schism to continuum? The problematic relationship between expert and lay
      knowledge--an exploratory conceptual synthesis of two qualitative studies.
AB  - Ideas about lay and expert knowledge increasingly underscore debates within
      qualitative health research. In this article, the authors develop an exploratory
      synthesis of two qualitative studies in which they critique the lay-expert
      divide, suggesting instead a spectrum of knowledge(s) about health and scientific
      issues. In the original studies, the researchers examined food risks and
      alternative medicine, and they shared an interest in the lay-expert knowledge
      relationship. Reinterpreting each study in the light of the other led to greater
      conceptual development. Three mutual themes emerged and are presented with
      discussion of their contribution to wider theoretical debates. This worked
      example indicates that researchers can achieve valuable additional conceptual
      development through the cross-fertilization of ideas across qualitative studies
      united not by common health topics but by shared conceptual concerns.

PMID- 15961873
TI  - Life versus disease in difficult diabetes care: conflicting perspectives
      disempower patients and professionals in problem solving.
AB  - Conflicts in problem solving are known from diabetes research on patients with
      good glycemic control but have rarely been studied in the care of patients with
      poor glycemic control. Equally, the different perspectives of health care
      providers and patients have not been a focus in previous studies. The authors
      studied the interactions between health care providers and 11 diabetes patients
      with poor glycemic control in a grounded theory study at a Danish university
      hospital. Keeping Life and Disease Apart was identified as a core category. It
      involved a pattern of conflicts both between and within patients and health
      professionals, which disempowered them in problem solving. Three approaches to
      problem solving were identified: A compliance-expecting approach kept the pattern
      unchanged, a failure-expecting approach deadlocked the pattern, and a mutuality
      expecting approach appeared to neutralize the conflict.

PMID- 15961874
TI  - Observations of shipboard illness behavior: work discipline and the sick role in
      a residential work setting.
AB  - In this article, the author reports on a small-scale ethnographic study of
      illness behavior in a residential work setting, a large merchant cargo ship with
      a multinational crew. Although parallels with previous observational work on
      illness behavior in residential settings (where illnesses result in treatment
      only if there is a break in accommodation to symptoms) exist, it is clear that
      type of setting is pivotal in shaping illness careers. Here, accommodation to
      symptoms was overlain by the economic imperative to keep the ship functioning:
      Management feared that the right to the sick role would allow "malingering,"
      whereas workers feared adoption of the sick role would exclude them from
      employment. In the latter case, the worker might experience illness or disability
      in a manner parallel to a Marxist analysis of the product of workers'labor: as an
      alien object of control and oppression, grounds for his or her removal from the
      workforce.

PMID- 15961875
TI  - Older stroke patients' negotiations within the hierarchic medical context.
AB  - A stroke can affect a person's whole being and make him or her feel helpless and
      insecure. In this study, the authors aimed to analyze from a gender perspective
      how elderly women and men responded to treatment and care after stroke in the
      acute care setting. They used a strategic selection procedure in this qualitative
      follow-up interview study, in which 7 women and 5 men aged 75 to 83 participated.
      Personal interviews were performed, tape-recorded, transcribed verbatim, and
      analyzed in accordance with grounded theory. In the hierarchic medical context,
      the participants used four kinds of negotiations. These negotiations were either
      resistant (striving for autonomy and criticizing the care) or adjustive
      (following the rules and building alliances) to the hierarchic structure. The
      authors discuss how the concepts of power from above versus power from below can
      be applied in the hierarchic medical context.

PMID- 15961876
TI  - HIV-positive patients and the doctor-patient relationship: perspectives from the
      margins.
AB  - The doctor-patient relationship and the medical consultation are important
      resources for the health work of people living with chronic illness. In this
      article, the author examines physician-based outpatient health care from the
      standpoint of women and men who live with HIV in conditions of economic and
      social marginality. She draws on focus group and interview conversations with 79
      HIV-positive individuals in southern Ontario. Using the approach of institutional
      ethnography, she offers a close reading of patients' descriptions of what they
      consider good doctoring. Areas of best practice that enhance access to health
      care examined here include doctors' interactional styles, ways of providing
      treatment options and treatment information, and ways of addressing the specific
      needs and life circumstances of patients living in poverty and social
      marginality.

PMID- 15961878
TI  - Interviewing young children: explicating our practices and dilemmas.
AB  - Qualitative research studies have demonstrated that very young children can
      provide important insights into their daily lives and health experiences. Despite
      the shift to include children's perspectives in research and document principles
      related to good data collection with children, there has not been a parallel move
      within the scholarly community to lay bare the practical challenges inherent in
      conducting interviews with children. In this article, the authors consider the
      degree to which well-known standards for qualitative research apply to research
      interviews with young children. They make practical recommendations that build on
      existing theoretical work about the conduct of qualitative interviews with young
      children.

PMID- 15961877
TI  - Normalization in families raising a child who is medically fragile/technology
      dependent and developmentally delayed.
AB  - The authors combined and analyzed parent data from two field studies examining
      family experiences in raising children who were both medically fragile and
      developmentally delayed or disabled to compare these families' experiences to
      published attributes of normalization. Normalization is usually considered a
      useful conceptual and coping strategy for families of children with chronic
      conditions, but it has not been examined in families whose children have both
      complex physical and developmental disabilities. Developmental delays compounded
      the effects of the children's physical chronic conditions, severely affecting how
      families organized and managed their daily lives, with the result that families
      did not fit currently established attributes of normalization. Instead, parents
      recognized normal and positive aspects of their lives while acknowledging the
      profound challenges that their families faced. Parents concluded that it was
      possible to have a good life that was not necessarily normal by usual standards.

PMID- 15961879
TI  - What about focus group interaction data?
AB  - The purpose of this article is to discuss issues related to group interaction
      data in focus groups. How should it be analyzed and reported? The author
      addresses these questions using qualitative research approaches with examples
      from her research to foster further discussion regarding focus group research.

PMID- 15961881
TI  - Processing color figures: that was then, this is now.

PMID- 15961880
TI  - Research with participants in problem experience: challenges and strategies.
AB  - In this article, the author draws on his years of fieldwork contact with
      participants who experience various problem events in life, including truancy,
      running away, delinquency, vagrancy, homelessness, gang membership, criminal
      conviction, drug abuse, domestic abuse, sexual deviance, sexually transmitted
      disease, mental disorder, and infection with HIV/AIDS. He examines challenges
      from and explores strategies for research with participants in problem
      experience, on the matter of recruitment, participation, empowerment, cross
      checking, and researcher protection. He includes examples to illustrate how
      generalizations in each category are made from real-world observation.

PMID- 15961883
TI  - Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in
      development, repair, and cancer.
AB  - Intestinal myofibroblasts are alpha-smooth muscle actin-positive stromal cells
      that exist as a syncytium with fibroblasts and mural cells in the lamina propria
      of the gut. Through expression and secretion of cytokines, chemokines, growth
      factors, prostaglandins, and basal lamina/extracellular matrix molecules, as well
      as expression of adhesion molecules and receptors for many of the same soluble
      factors and matrix, myofibroblasts mediate information flow between the
      epithelium and the mesenchymal elements of the lamina propria. With the use of
      these factors and receptors, they play a fundamental role in intestinal
      organogenesis and in the repair of wounding or disease. Intestinal neoplasms
      enlist and conscript myofibroblast factors and matrix molecules to promote
      neoplastic growth, carcinoma invasion, and distant metastases.

PMID- 15961882
TI  - AMP-18 protects barrier function of colonic epithelial cells: role of tight
      junction proteins.
AB  - Antrum mucosal protein (AMP)-18 and a synthetic peptide of amino acids 77-97 have
      mitogenic and motogenic properties for epithelial cells. The possibility that AMP
      18 is also protective was evaluated in the colonic mucosa of mice and monolayer
      cultures of human colonic epithelial Caco-2/bbe (C2) cells. Administration of AMP
      peptide to mice with dextran sulfate sodium (DSS)-induced colonic injury delayed
      the onset of bloody diarrhea and reduced weight loss. Treatment of C2 cells with
      AMP peptide protected monolayers against decreases in transepithelial electrical
      resistance induced by the oxidant monochloramine, indomethacin, or DSS. A
      molecular mechanism for these barrier-protective effects was sought by asking
      whether AMP peptide acted on specific tight junction (TJ) proteins. Immunoblots
      of detergent-insoluble fractions of C2 cells treated with AMP peptide exhibited
      increased accumulation of specific TJ proteins. Occludin immunoreactivity was
      also increased in detergent-insoluble fractions obtained from colonic mucosal
      cells of mice injected with AMP peptide. Observations using laser scanning
      confocal (CF) microscopy supported the capacity of AMP peptide to enhance
      accumulation of occludin and zonula occludens-1 in TJ domains of C2 cell
      monolayers and together with immunoblot analysis showed that the peptide
      protected against loss of these TJ proteins following oxidant injury. AMP peptide
      also protected against a fall in TER during disruption of actin filaments by
      cytochalasin D and stabilized perijunctional actin during oxidant injury when
      assessed by CF. These findings suggest that AMP-18 could protect the intestinal
      mucosal barrier by acting on specific TJ proteins and stabilizing perijunctional
      actin.

PMID- 15961884
TI  - Dual action of prostaglandin E2 on gastric acid secretion through different EP
      receptor subtypes in the rat.
AB  - We examined the role of prostaglandin E (EP) receptor subtypes in the regulation
      of gastric acid secretion in the rat. Under urethane anesthesia, the stomach was
      superfused with saline, and the acid secretion was determined at pH 7.0 by adding
      50 mM NaOH. The acid secretion was stimulated by intravenous infusion of
      histamine or pentagastrin. Various EP agonists were administered intravenously,
      whereas EP antagonists were given subcutaneously 30 min or intravenously 10 min
      before EP agonists. PGE(2) suppressed the acid secretion stimulated by either
      histamine or pentagastrin in a dose-dependent manner. The acid inhibitory effect
      of PGE(2) was mimicked by sulprostone (EP(1)/EP(3) agonist) but not butaprost
      (EP(2) agonist) or AE1-329 (EP(4) agonist). The inhibitory effect of sulprostone,
      which was not affected by ONO-8711 (EP(1) antagonist), was more potent against
      pentagastrin- (50% inhibition dose: 3.6 mug/kg) than histamine-stimulated acid
      secretion (50% inhibition dose: 18.0 mug/kg). Pentagastrin increased the luminal
      release of histamine, and this response was also inhibited by sulprostone. On the
      other hand, AE1-329 (EP(4) agonist) stimulated the acid secretion in vagotomized
      animals with a significant increase in luminal histamine. This effect of AE1-329
      was totally abolished by cimetidine as well as AE3-208 (EP(4) antagonist). These
      results suggest that PGE(2) has a dual effect on acid secretion: inhibition
      mediated by EP(3) receptors and stimulation through EP(4) receptors. The former
      effect may be brought about by suppression at both parietal and enterochromaffin
      like cells, whereas the latter effect may be mediated by histamine released from
      enterochromaffin-like cells.

PMID- 15961885
TI  - Events at the host-microbial interface of the gastrointestinal tract IV. The
      pathogenesis of Helicobacter pylori persistence.
AB  - Long-term interactions between Helicobacter pylori and humans significantly
      increase the risk for peptic ulcer disease and noncardia gastric adenocarcinoma.
      The vast majority of infected persons remain persistently colonized unless a
      targeted antibiotic regimen is employed; thus regulation of inflammation by H.
      pylori is governed by levels of host-bacteria equilibria that are not found
      during cellular interactions with acute enteric pathogens. It is important to
      gain insight into mechanisms that regulate immune evasion by H. pylori not only
      to develop more effective treatments for disease, but also because such knowledge
      may serve as a paradigm for the role that other chronic infectious agents play in
      the genesis of pathological lesions that arise from inflammatory foci.

PMID- 15961887
TI  - Case finishing checklist.

PMID- 15961886
TI  - Cytochrome P4502E1 primes macrophages to increase TNF-alpha production in
      response to lipopolysaccharide.
AB  - Kupffer cells become activated in response to elevated levels of LPS during
      ethanol feeding, but the role of ethanol in the molecular processes of activation
      remains unclear. Because cytochrome P4502E1 (CYP2E1) is upregulated in Kupffer
      cells after ethanol, we hypothesized that this effect primes Kupffer cells,
      sensitizing them to increase TNF-alpha production in response to LPS. However,
      cultured Kupffer cells rapidly lose their CYP2E1. This difficulty was overcome by
      transfecting CYP2E1 to RAW 264.7 macrophages. Macrophages with stable increased
      CYP2E1 expression (E2) displayed increased levels of CD14/Toll-like receptor 4,
      NADPH oxidase and H2O2, accompanied by activation of ERK1/2, p38, and NF-kappaB.
      These increases primed E2 cells, sensitizing them to LPS stimuli, with
      amplification of LPS signaling, resulting in increased TNF-alpha production.
      Diphenyleneiodonium, a NADPH oxidase inhibitor, and diallyl sulfide, a CYP2E1
      inhibitor, decreased approximately equally H2O2 levels in E2 cells, suggesting
      that NADPH oxidase and CYP2E1 contribute equally to H2O2 generation. Because
      CYP2E1 expression also enhanced the levels of the membrane localized NADPH
      oxidase subunits p47phox and p67phox, thereby contributing to the oxidase
      activation, it may augment H2O2 generation via this mechanism. H2O2, derived in
      part from NADPH and CYP2E1, activated ERK1/2 and p38. ERK1/2 stimulated TNF-alpha
      production via activation of NF-kappaB, whereas p38 promoted TNF-alpha production
      by stabilizing TNF-alpha mRNA. Oxidant generation after CYP2E1 overexpression
      appears to be central to macrophage priming and their sensitization to LPS.
      Accordingly, CYP2E1 priming could explain the sensitization of Kupffer cells to
      LPS activation by ethanol, a critical early step in alcoholic liver disease.

PMID- 15961889
TI  - Bjorn U. Zachrisson, DDS, MSD, PhD, on current trends in adult treatment, part 2.
      Interview by Robert G. Keim.

PMID- 15961890
TI  - SureSmile: a report of clinical findings.

PMID- 15961891
TI  - Surgical guide for optimal positioning of mini-implants.

PMID- 15961893
TI  - Temporary replacement of missing teeth using lingual retainers.

PMID- 15961892
TI  - Accurate polyvinyl siloxane impressions.

PMID- 15961894
TI  - [Relation between storage stability and molecular mobility in cells of seed and
      pollen].
AB  - In recent years, it is possible to know the optimal storage conditions of seeds
      and pollen from the relationship between storage stability and molecular
      mobility, which can be successfully determined by techniques of spin probe,
      electron paramagnetic resonance (EPR) and saturation transfer electron
      paramagnetic resonance spectroscopy (ST-EPRS). This is theoretically and
      practically important to germplasm conservation. This review focuses on the
      current advances in the research of molecular mobility and storage stability of
      seed and pollen.

PMID- 15961895
TI  - Uptake and transport of calcium in plants.
AB  - Recently, research on Ca(2+) transport in plants has been focused on cellular and
      molecular level. But the uptake, transport and distribution are also very
      important for calcium to accomplish its function at whole plant level. There are
      many cells along the way of transport of Ca(2+) from root to shoot, and Ca(2+)
      passes either through the cytoplasm of cells linked by plasmodesmata (the
      symplast) or through the spaces between cells (the apoplast), which include
      Ca(2+) uptake by root cells, Ca(2+) transport from root cortex to and through the
      xylem, and then out of it into leaves or fruits. Ca(2+) channels, Ca(2+)/H(+)
      antiporter and Ca(2+)-ATPase play roles in the uptake and transport of Ca(2+) in
      root cells. To be transported from root surface to xylem, Ca(2+) needs to
      traverse endodermal cells and xylem parenchyma cells. Endodermal Casparian band,
      the main barrier for the apoplastic movement of ions into the stele, compels some
      Ca(2+) to enter root symplast through Ca(2+) channels in endodermal cells and
      then reach xylem parenchyma. Ca(2+)-ATPase may drive Ca(2+) into the stelar
      apoplast from xylem parenchyma. Some Ca(2+) effuses from endodermal cell and then
      get to xylem through apoplastic pathway. Ca(2+) is transported in plant xylem
      vessel in chelate form and the speed of water flow is the key factor Ca(2+)
      transport via xylem in trunk. There are both apoplastic and symplastic pathways
      of Ca(2+) transport in fruit or leaf tissue too.

PMID- 15961896
TI  - Agrobacterium-mediated transformation of Malus robusta with tomato iron
      transporter gene.
AB  - The tomato iron transporter gene (LeIRT2) was introduced to Malus robusta Rehd.
      via Agrobacterium-mediated transformation to produce iron-deficiency tolerant
      apple rootstock. A total of 19 putative transformants were obtained, 11 of which
      were verified by PCR amplification to carry a fragment of the transgene. Among
      them, nine were confirmed to carry the transgene by Southern blot analysis with
      one to three copies of the transgene integrated into the plant genome. Two
      transgenic plants, one carrying one copy and the other three copies of the
      transgene, were hydroponically cultured to test their tolerance to iron
      deficiency, which was found only in the transgenic plant with a single copy,
      which weighted 21%-4% greater than those of the control plants.

PMID- 15961897
TI  - [Effects of exogenous nitric oxide donor on germination and activities of
      hydrolytic enzymes in wheat seed under osmotic stress].
AB  - Results in this paper showed that the effect of nitric oxide (NO) donor, sodium
      nitroprusside (SNP), which could promote the germination of wheat seeds under
      osmotic stress, was through enhancing imbibition using water content
      determination and imbibition analysis of wheat seed. SNP could also enhance
      amylase isozyme I activities, accelerate the liquefaction of endosperms, while
      have no effect on esterase. Moreover, SNP could strongly increase the sugars,
      such as the fructose, glucose and sucrose contents in wheat seeds during early
      germination (12 h) under normal conditions. When the seeds were treated with SNP
      with or without PTIO, an NO scavenger, and different exogenous sugars, i.e.
      fructose, glucose and sucrose, it was found that these sugars might activate
      amylase isozyme I activity mediated by the signal molecule NO to start the early
      stage of germination.

PMID- 15961898
TI  - [Specific expression of the foreign gene regulated by the rice rbcS promoter in
      transgenic rice].
AB  - To use different types of promoters in transgenic rice research, the 5'-upstream
      regulation region of rice Rubisco small subunit gene (rbcS) was cloned from a
      Chinese cultivar Wuyunjing 8, and its sequences were confirmed by comparison with
      the known genome sequences of both japonica and indica rice. The cloned rbcS
      promoter was fused to the 5'-upstream of GUS (beta-glucuronidase) coding region
      in a binary vector, and introduced into rice by Agrogacterium-mediated
      transformation. The integration of the rbcS-GUS fusion gene in transgenic rice
      was confirmed by PCR analysis. The results of both histochemical staining and
      quantitative analysis of GUS activity showed that the expression level of GUS
      fusion gene was significantly stronger in leaf blade and sheath than in other
      organs of transgenic rice plants, and the GUS activity was restricted to the
      mesophyll cells of leaf tissue, which showed that the rice rbcS promoter could
      control not only the tissue- but also the cell-specific expression of foreign
      genes in transgenic rice. The present results also demonstrated that light
      induction had a significant effect on the enhancement of transgene's expression
      when regulated by the rice rbcS promoter in transgenic rice. Our results showed
      that the rice rbcS promoter might be very useful for the expression of target
      genes in transgenic rice, with particularly high efficiency in leaf tissues.

PMID- 15961899
TI  - [The characteristics of nuclear/cytoplasmic genomes of asymmetric somatic hybrid
      of Daucus carota var. sativa and Swertia mussotii].
AB  - Protoplasts of Swertia mussotii irradiated by ultra-violet light (UV) 260
      microW/cm(2) were fused with protoplasts of Daucus carota var. sativa using the
      PEG method. Analysis of 5S rDNA spacer sequences and random amplified polymorphic
      DNA (RAPD) showed the presence and combination of nuclear DNA from both parents.
      All hybrids mainly contained genomes of D. carota (receptor) RAPD bands, and a
      few donor RAPD bands of S. mussotii. There is no obvious relationship between the
      nuclear DNA composition was not affected by UV-dosage. SSR analysis of
      chloroplast DNA of the hybrid clones further revealed that cpDNAs of the parents
      were integrated and recombined in the hybrids randomly.

PMID- 15961900
TI  - Cloning and expression analysis of CRY2 gene in Sorghum bicolor.
AB  - CRY2 is the apoprotein of cryptochrome 2 and CRY2 cDNA has been cloned from
      Sorghum bicolor in this study. The results of sequence analysis shows that it
      contains a complete open reading frame encoding a predicted protein of 690 amino
      acids sharing 87% identity with the CRY2 of rice, but only 45.5% with that of
      Arabidopsis and 57% with that of tomato. The DNA sequence of sorghum CRY2
      contains three introns and four exons. RT-PCR results show that CRY2 has been
      transcribed in root, leaf and mesocotyl in sorghum seedlings. CRY2 protein has
      been shown by Western blot analysis to be present in mesocotyl, leaf and root,
      and to be accumulated in the dark and to be degraded under blue light.

PMID- 15961901
TI  - [Fragment length polymorphism of Wx-B1 gene digested by BamHI and its relation to
      amylose content of wheat].
AB  - There are two types of starch, amylose and amylopectin of flour. Amylose content
      (AC) is significantly negatively correlated with noodle quality. The waxy gene
      (Wx) encodes the granule-bound starch synthase (GBSS, EC 3.4.1.11), or Wx
      protein, is responsible for the synthesis of amylose in wheat. Common wheat is
      allohexaploid, it has three different Wx proteins: Wx-A1, Wx-B1, and Wx-D1.
      Consequently, amylose content and pasting properties of starch were influenced by
      the lack of the Wx-B1 protein, followed by that of Wx-D1, and Wx-A1. Using STS
      (sequence-tagged sites) primers, the sequences were amplified near the 4th intron
      region, and fragments amplified were digested by BamHI in 35 wheat cultivars. The
      results indicate that some fragments can be digested and the other cannot. The
      fragments digested showed two length polymorphism, and the length is negatively
      correlated with amylose content. The fragment in many cultivars with amylose
      content above 20% can be digested by BamHI, while those with amylose content
      below 20% cannot. All these indices demonstrate that there is variation exists in
      amplified region of Wx-B1 gene. This can be useful in breeding program to select
      wheat cultivars with different amylose content, and improve wheat quality.

PMID- 15961902
TI  - [Changes in polyamine levels in Citrus sinensis Osb. cv. Valencia callus during
      somatic embryogenesis].
AB  - Somatic embryogenetic capability and changes in polyamine level and their
      relationship were analyzed using the long-term (8 years) subcultured calli of
      Citrus sinensis Osb. cv. Valencia as materials. The results showed that
      endogenous polyamine contents in embryogenic calli were higher than those in non
      embryogenic calli, and the embryogenetic capability was positively correlated to
      the levels of endogenous polyamines. When the calli were transferred to a
      differentiation medium, the putrescine content rapidly increased and reached a
      peak, then fell gradually. Applying exogenous putrescine raised the embryogenesis
      frequency and endogenous putrescine level. It indicated that increase in
      putrescine content at early stage of differentiation promoted embryogenesis. With
      the development of somatic embryo, spermidine content reached its the highest
      level at globular embryo stage, spermine content rose and reached a peak at a
      later stage of globular embryo development. Furthermore, changes of the
      putrescine, spermidine and spermine contents during somatic embryogenesis were
      similar in Valencia calli which had different ploidy levels, but their contents
      decreased following the increasing of ploidy level. Changes in arginine
      decarboxylase activity were positively correlated to the polyamine levels, which
      suggest that the later is a key factor in regulating the polyamine levels during
      somatic embryogenesis in citrus plants.

PMID- 15961903
TI  - [The relationship between activities of chitinase and beta-1,3-glucanase and
      resistance to rhizomania in sugar beet].
AB  - The relationship between activities of chitinase and beta-1,3-glucanase and
      resistance to rhizomania of sugar beet were studied in diseased soil and disease
      free soil by using a method of comparative physiology. Two resistant varieties
      and two susceptible ones of sugar beet were used in this experiment. Chitinase
      and beta-1,3-glucanase activities of the resistant varieties were higher than the
      susceptible ones in either diseased soil or disease-free soil. There is a
      positive correlation between chitinase, beta-1,3-glucanase activity and yield of
      beet in diseased soil, suggesting that pathogen infection can induce resistance
      to rhizomania through activating chitinase and beta-1,3-glucanase.

PMID- 15961904
TI  - [The relationship between the desiccation-induced browning and the metabolism of
      active oxygen and phenolics in pericarp of postharvest longan fruit].
AB  - Longan (Dimocarpus longan Lour.) fruits are very susceptible to water loss and
      pericarp browning, and postharvest pericarp browning is the most important
      factors degrading the quality of longan fruit and shorting storage life. Pericarp
      browning has been attributed to desiccation, chilling, heat stress, senescence
      and pest or pathogen attack. Desiccation is the most main factor of induced
      pericarp browning in longan. The relationship between water loss from pericarp
      and pericarp browning in longan cv. Fuyan fruits using open plastic punnets and
      sealed polyethylene bags at 10 degrees C +/-1 degrees C and 50% relative
      humidity, and the effect of pericarp water loss of the fruit on active oxygen
      metabolism and phenolics metabolism were investigated. Water loss resulted in
      rapid pericarp browning. Development of pericarp browning was higher with higher
      rate of water loss from pericarp and storage time (from 0 to 6 days). Water loss
      from pericarp was positively correlated with pericarp browning index
      significantly (P<0.01). Water loss from pericarp resulted in reduced activities
      of reactive-oxygen-scavenging enzymes (SOD, CAT, APX and GR), decreased amounts
      of endogenous antioxidant substances (AsA and GSH), and increased rates of O(
      .)(2) production, MDA content and relative leakage rate, which showed that
      membrane structure was broken. Water loss from pericarp resulted in an increase
      in activity of PPO, and obvious reductions in total phenolic and flavonoid
      contents, whereas there was not obvious change in anthocyanin content. These
      results show that phenolics and flavonoids are the main substrates for PPO during
      desiccation-induced browning. Water loss from pericarp caused a significant
      increase in activity of POD, which also plays an important role in desiccation
      induced browning in pericarp of longan fruit. Water loss from pericarp caused an
      increase in pH value, which resulted in changes in anthocyanin structure and
      color, the degradation of anthocyanin became easier. The results suggest that
      desiccation-induced browning of longan pericarp may be due to a decrease in
      activities of reactive-oxygen-scavenging enzymes and amounts of endogenous
      antioxidant substances, an accumulation of active oxygen, an increase in membrane
      lipid peroxidation, an injury of the integrity of cellular membrane structure,
      which, in turn, may cause cellular decompartmentation, resulted in PPO and POD,
      located in plastid and other organelle, to come into contact with phenolic and
      flavonoid substrates, located in vacuole, to form brown polymers.

PMID- 15961905
TI  - [Effects of Triton X-100 on the oxygen uptake rate of photosystem I particles
      treated at 70 degrees C].
AB  - The characteristics including oxygen uptake rates, fluorescence spectra and
      absorption spectra of photosystem I particles with or without Triton-X 100
      treatment before or after the incubation at 70 degrees C for 10 min were
      compared. The oxygen uptake rates of photosystem I particles decreased after
      being incubated at 70 degrees C for 10 min, which could be recovered by the
      addition of Triton-X 100. Singlet oxygen was formed when the light-harvesting
      complex I was separated from the core complex of photosystem I, which resulted in
      high oxygen uptake rate. There was much difference in the fluorescence spectra of
      photosystem I particles between photosystem I particles treated with Triton-X 100
      after the incubation at 70 degrees C for 10 min or not, which implies the ability
      of Triton-X 100 to promote the recovery of photosystem I particles after the
      incubation at 70 degrees C for 10 min.

PMID- 15961906
TI  - [Gene expression and activity regulation of two calmodulin binding protein
      kinases in tobacco seedling].
AB  - Two different calmodulin-binding protein kinase cDNAs (NtCBK1/2) have been
      isolated from tobacco. To understand the CBK protein activity regulation, we
      compared the activity regulation of NtCBK1 and NtCBK2 by pH, Mg(2+) concentration
      and Na(+) concentration. We found the autophosphorylation of NtCBK1/2 reached the
      maximum in pH 7.5 and 8 respectively; Mg(2+) and Na(+) shown different effects on
      the activity of NtCBKs, high and low Mg(2+) concentrations both inhibited the
      activity of NtCBKs, but Na+ had little effect on the kinase activity. In
      addition, to obtain further insight about the physiological roles of individual
      NtCBKs, we detected the expression profiles of CBKs. The results revealed
      different patterns of expression of NtCBK1 and NtCBK2. Both are largely expressed
      in leaf and flower; but in stem and root, NtCBK1 gene had stronger expression
      than NtCBK2. NtCBK2 expression was induced by GA treatment, while NtCBK1
      expression remained unchanged under GA treatment. Expression of both NtCBK1 and
      NtCBK2 increased in response to salt stress, the former to a greater extent, and
      both expressions did not change under high/low temperature, drought, NAA and ABA
      treatments.

PMID- 15961907
TI  - [Effects of salt stress on the growth and Na+ and K+ contents in Aeluropus
      littoralis var. sinensis Debeaux].
AB  - After seedlings of Aeluropus littoralis var. sinensis Debeaux were treated with
      different NaCl concentrations (0-200 mmol/L) for 17 days, some physiological
      indexs were measured. With an increase in NaCl concentration, the growth of A.
      littoralis was inhibited gradually. There was no optimum salt concentration, and
      the shoots were more sensitive than the roots. The proportion of organic dry
      weight in total dry weight increased, which implies that the contribution of
      organic matter to osmotic adjustment increased with salinity. After being treated
      with the inhibitor--benzene-sulphuric acid choline which could inhibit the salt
      glands to secrete the salinity outside the body. The Na(+) and K(+) contents of
      leaves increased, while the amount of Na(+) and K(+) decreased in the secretion,
      and the growth was severely inhibited. After being treated with NaCl 100 mmol/L,
      the relative Na(+) contents in the cap cells and basal cells determined by X-ray
      microanalysis were from about one to more than triple those of the epidermis and
      mesophyllous cells, it shows that the salt glands could effectively collect Na(+)
      from other cells and secrete them outside the body to keep normal physiological
      function.

PMID- 15961908
TI  - [Changes in trans-thylakoid membrane proton motive force induced by treatments
      with red and far-red light in Dunaliella salina].
AB  - The changes in trans-thylakoid membrane proton motive force caused by red light
      and caused by far-red light in the halotolerant green alga, Dunaliella salina are
      investigated. Irradiation with red light decreased the intensity of the fast
      phase of millisecond delayed light emission (ms-DLE) in D. salina, and far-red
      light led to the opposite effects. Under low temperature conditions (4 degrees
      C), red light still decreased ms-DLE fast phase intensity, however, far-red light
      did not enhance the ms-DLE fast phase intensity as it did at room temperature. In
      the presence of the uncoupler, nigericin, which eliminates the proton gradient
      across the thylakoid membrane, there was still a decrease in ms-DLE after red
      light irradiation, while far-red light had no stimulatory effects anymore. The
      far-red light-induced increase in ms-DLE fast phase is thus suggested to be due
      to the proton gradient formed by water oxidation in photosystem II. Previous
      studies with higher plants revealed that far red light increased ms-DLE fast
      phase intensity slightly, while red light caused a transient increase in ms-DLE
      fast phase intensity followed by a gradual decrease. Taken together, green algae
      differ from higher plants with respect to red light- and far red light-induced
      changes in ms-DLE. The possible reason is discussed.

PMID- 15961910
TI  - [Transient expression of GUS gene controlled by different regulator sequences in
      rice and Populus tomrutosa].
AB  - GUS gene controlled by several kinds of regulator sequences (promoters, TMVOmega
      enhancer and fragments of 18S rRNA gene from Arabidopsis thaliane) were
      introduced into the calli of rice and Populus tomrutosa respectively by gene gun.
      The transient expression of GUS gene in the calli of rice and P. tomrutosa was
      investigated. The results showed: (1) in the calli of rice, Ubil promoter was the
      most effective one among the several regulator sequences and CaMV35S with
      fragments of 18S rRNA gene is the least effective one; (2) in the calli of P.
      tomrutosa, CaMV35S promoter with 18S rDNA fragments was the most effective one
      among the several regulator sequences; and (3) tandem CaMV35S-Ubil promoter with
      TMVOmega sequence could not enhance significantly the expression of GUS gene in
      the calli of rice and P. tomrutosa.

PMID- 15961909
TI  - [O2-* burst of tobacco leaves triggered by Erwinia carotovora subsp. carotovora
      inoculation].
AB  - O(-.)(2) production based on chemical method by Ecc-treated intact tobacco leaves
      was observed. It showed a long-lasting one-phase course beginning 1 h and ending
      14 h after Erwinia carotovora subsp. carotovora (Ecc) was inoculated. In Ecc
      treated leaves, O(-.)(2) production rate of 3 h is 2 times of 1 h, and of 10 h it
      remains 1.7 times. It decreases rapidly between 10 h and 14 h, at 14 h it falls
      to the level before inoculation. This is a completely different course from the
      widely accepted two-phase course obtained from suspension-cultured cells.
      Electron spin resonance (ESR) spectrum of O(-.)(2) produced by intact tobacco
      leaves after Ecc inoculation 2 h and 6 h was also observed, the amplitude of 6 h
      is larger than of 2 h in Ecc-treated group. In the control group, there is no
      difference between the amplitude of 2 h and 6 h. This indicated that O(-.)(2)
      amount of Ecc-treated group is higher than of the control group, which is the
      same result as obtained through chemical method. The ESR spectrum of O(-.)(2)
      produced by chloroplasts and mitochondria from tobacco leaves after 2 h and 6 h
      after Ecc inoculation were observed. In chloroplast experiment, the amplitude of
      6 h was larger than of 2 h in Ecc-treated group while it was the same in the
      control group. ESR spectrum of O(-.)(2) produced by mitochondria was proved to be
      a same result after a careful comparison, in spite of a greater difference
      between 2 h and 6 h in control group than chloroplast experiment. The fact that
      spectra of these two organelles were both synchronous with that of intact leaves
      implied that these two organelles possibly participated in cellular O(-.)(2)
      burst. Chloroplasts in the dark showed no ESR spectrum 2 h and 6 h after Ecc
      inoculation in Ecc-treated group as well as in the control group, indicating that
      O(-.)(2) in the chloroplast probably originated from the photosynthetic electron
      transport process.

PMID- 15961912
TI  - [Team communication needed in treatment for denture prosthesis. 1) Opinion from
      dentist's standpoint].
AB  - The objectives of using a denture to treat a defect are preservation of remaining
      tissue and improvement in the functional recovery rate. Close cooperation between
      dentist and dental technician and a shared understanding of fundamental knowledge
      and technology, from denture design to production, are indispensable in order to
      successfully achieve a combination of these objectives. Furthermore, accurate
      communication from dentist to dental technician of all patient information gained
      from the preoperative examination and necessary for production of the prosthesis
      is essential for a successful treatment outcome. This information should be
      shared by both the dentist and the dental technician. It is extremely important
      to describe this information appropriately and to append other information as
      needed in order to convey this information from the dentist to the dental
      technician by means of a dental technician specification. While this exchange of
      opinions by means of accompanying materials is of course useful in the denture
      production process, these materials are also valuable for re-evaluating the
      design of the prosthesis and handling by the technician in case a problem related
      to preservation of remaining tissue or improvement in the functional recovery
      rate arises during a subsequent visit by the patient. It is important for the
      dentist and the dental technician to consider the following six factors using the
      same criteria when treating a patient using a removable partial denture: (1)
      minimization of denture movement, (2) occlusion, (3) reduction of burden on the
      abutment, (4) consideration of periodontal tissue, (5) consideration of
      sensation, and (6) aesthetic considerations. To that end, the authors have found
      clinical application of a "design chart" to be useful.

PMID- 15961911
TI  - [Current status of team communication considered from a questionnaire survey on
      the laboratory prescription card].
AB  - Team communication between dentists and dental technicians offers high-quality
      medical treatment for patients. When dentists and dental technicians understand
      dental treatments and laboratory procedures and talk to each other from an equal
      standpoint, good team communication between them can be established. However,
      undergraduate dental students do not sufficiently understand the content and
      processes of laboratory procedures because the subjects and hours in laboratory
      procedures have been reduced at present. Education on team communication between
      dentists and dental technicians is not sufficiently included in the training
      content of postgraduate training practice. It seems that at present, it is
      difficult for good team communication to be established between new graduate
      dentists and dental technicians. In view of this, the current status of the team
      communication between dentists and dental technicians in the present clinic was
      investigated, because a guideline for constructing team communications between
      dentists and dental technicians is given in the dental education before and after
      graduation. That is to say, the current status of the team communication of
      dentists and dental technicians was investigated by considering a questionnaire
      survey on the laboratory prescription card, which is the most important
      information means for connecting dentists with dental technicians in the dental
      clinic. The results were as follows: The entry items were insufficient on the
      laboratory prescription cards. Therefore, it is necessary to prepare such
      laboratory prescription cards that required items are entirely indicated as well
      as to enter them fully by dentists.

PMID- 15961913
TI  - [Team communication needed in treatment for denture prosthesis. 2) Opinion from
      dental technician's standpoint].
AB  - As for the team communication between clinical and technological sides in the
      denture treatment,a smooth cooperative teamwork must be established in its target
      treatment through individual adequate recognitions concerning the main points of
      sequential procedures from examination, diagnosis, therapeutic designing,
      impression taking and bite registration and then setting performed by a dentist
      on the clinical side as well as concerning the main points of technical
      procedures indirectly performed by a dental technician on the technological side
      in order to achieve the most improved preservation of remained tissues with an
      increased rate of functional restoration, being the final target of treatment. At
      present when an ultra-aged society is coming, the demand of denture treatment has
      been enhanced more and more. In response to the enhanced patient's demand,
      various modes of denture treatment have been introduced and the dental technology
      has advanced remarkably. In particular, a technical procedure by means of partial
      parallel milling representative of rigid support or of Konuskronen requires very
      complicated working processes. In addition, the elasticity is also required
      including such an occlusal construction as being harmonious with the jaw function
      or such tooth crown morphology as being prepared in consideration of periodontal
      tissues together with a lot of information from the clinical side required as
      well in the denture treatment. In this study, therefore, the dental technical
      procedures presently performed by referring to varied individual information are
      newly arranged and summarized so as that these complicated technical processes
      and working steps could be performed more easily and accurately.

PMID- 15961914
TI  - [Team communication needed in treatment for fixed prosthesis. 1) Opinion from
      dentist's standpoint].
AB  - It is important that a dentist and a dental technician share information about
      form and function of the restoration to be provided for the patient. The purpose
      of this paper is to discuss the methods and the contents of communication that a
      dentist establishes with a dental technician in treatment for fixed prosthesis.
      The communication is not one-way in which a dentist directs some work content to
      a dental technician; rather, it is a two-way communication of exchange that
      includes dental technician's knowledge and skill toward the dentist. A dentist
      must communicate with a dental technician to express four factors of
      biocompatibility, function, esthetics and biomechanics in the fixed prosthesis.
      Provisional restorations are used for embodiment as early as possible, and each
      other's communication enables smooth sharing of the image of the final
      prosthesis. It is necessary to inform the dental technician of the contents that
      are required for fabrication of fixed prosthesis and that cannot be obtained from
      the model. The fixed prosthesis satisfactory for the patient can be made through
      cooperation between dentist and dental technician. Furthermore, the strong
      relationship of mutual trust can realize more reliable fixed prosthesis.

PMID- 15961915
TI  - [Team communication needed in treatment for fixed prosthesis. 2) Opinion from
      dental technician's standpoint].
AB  - The fabrication of a fixed prosthesis is influenced by the communication between
      the dentist and the laboratory technician. Especially for tooth-colored
      restoration of anterior teeth, the laboratory technician has the difficult task
      of understanding the shade selected by the dentist and reproducing it in the
      final restoration. Conventional shade analysis techniques using the Vita shade
      guide often result in subjective analysis and a resultant miscommunication of
      color. Over the years, many different techniques including picture-taking,
      drawing of diagrams, and using multiple shade guides have been formulated to help
      overcome this problem. Recently, digital shade analysis systems have been
      designed to eliminate the subjectivity of color analysis and provide precise
      information for laboratory buildup and fabrication. However, even these
      techniques have not completely erased the difficulties involved in communicating
      the choice of the proper shade for tooth-colored restoration. Many dentists are
      only familiar with techniques they were taught in dental school and/or their
      residency program, and they are unaware of other, superior methods that can be
      used. This review introduces various shade analysis systems that can be performed
      in dental clinical practice. Further, it highlights the importance of
      communication between the dentist, technician, and patient for the fabrication
      and delivery of aesthetic restorations.

PMID- 15961916
TI  - [A study on the differences in function of free-sided and unilateral chewing].
AB  - PURPOSE: Unilateral chewing requires a greater number of chewing strokes up to
      the point of the first swallowing. The rate of storage of ground food particles
      in the oral vestibule is said to be high during unilateral chewing. However,
      influence of the masticatory method, that is free-sided or unilateral chewing,
      involved in masticatory efficiency has not been elucidated. On that point, in
      order to clearly represent the effects that free-sided (bilateral) chewing and
      unilateral chewing have on the chewing efficiency, our purpose was to examine the
      difference of the functions of both free-sided chewing and unilateral chewing.
      METHODS: We used 116 dentate subjects with normal occlusal relations, and
      compared the number of chewing strokes for peanuts up to the point of the first
      swallowing (abbreviated as "chewing strokes") for both free-sided chewing and
      unilateral chewing. Following this, we made calculations regarding the amount of
      saliva secretion, occlusal force, and contact points of posterior teeth. Based on
      the averages of three parameters (saliva secretion, occlusal force and contact
      points of posterior teeth), all the subjects were classified into two groups
      (high score group and low score group). In the two groups, we counted the
      difference in the number of free-sided chewing and unilateral chewing. And also
      in two groups, the amount of remaining coarse particles immediately prior to the
      first swallowing was investigated between free-sided chewing and unilateral
      chewing. RESULTS: The number of chewing strokes by free-sided chewing for all
      subjects was 10% less than that of unilateral chewing. Furthermore, the numbers
      of chewing strokes by free-sided chewing were all less than those of unilateral
      chewing in both groups on three parameters. The amount of remaining coarse
      particles by free-sided chewing was significantly smaller than that of unilateral
      chewing in the low score group of saliva secretion and occlusal force.
      CONCLUSIONS: The number of chewing strokes by free-sided chewing was less than
      that of unilateral chewing in both of the high score group and low score group on
      the amount of saliva secretion, occlusal force, and contact points of posterior
      teeth.

PMID- 15961917
TI  - [Investigation of meals in health care service facility].
AB  - PURPOSE: Oral care and oral treatment are promoted in health care service
      facilities. However, disorders of eating, mastication and swallowing and care
      management of meal were get behind. This study investigated them in health care
      service facilities. METHODS: Doctors who work in facilities were screened for
      care management of meal using questionnaire. Inpatients were screened for age,
      meal menu, vertical stop, prosthetic treatment, satisfaction of mastication and
      difference of meal menu in the home and in the facility. RESULTS: Doctors and
      care workers have little understanding of mastication. Inpatients were satisfied
      to be able to eat rice in the home and in the facility. It is of paramount
      importance to have remaining teeth, to maintain vertical stop and to have
      prosthetic treatment. CONCLUSIONS: Education on the importance of mastication is
      needed. The research results show that new action and diagnosis method for
      deciding menus aiming at mastication of steamed rice need to be developed.

PMID- 15961918
TI  - [Electroencephalogram evaluation of denture tolerance with different design of
      upper major connector].
AB  - PURPOSE: This study investigated the possibility of objectively evaluating
      denture tolerance with different designs of upper major connector through
      electroencephalographic examination. METHODS: Nine healthy dentate subjects wore
      five designs of palatal plates (All palatal type, Anterior palatal type,
      Horseshoe type, Palatal bar type, and Palatal strap type). Electromyograms (EMG)
      from the masseter and the posterior temporal muscles during mastication and
      electroencephalograms (EEG) before and after mastication were simultaneously
      recorded and analyzed. In addition to evaluation by visual analogue scale (VAS),
      questionnaire surveys consisting of five comfort parameters were also done.
      RESULTS: VAS values showed uncomfortable feeling for all questions on wearing
      each type of palatal plate, particularly the Total palatal type, Horseshoe type,
      and Palatal strap type. There were no significant differences between control and
      all palatal plates in EMG evaluations. After mastication, %alpha in EEG decreased
      and %beta increased, both significantly, compared with those before mastication.
      The slope of 1/f fluctuation in alpha-wave increased after mastication
      significantly. The variation of EEG (%alpha, %beta and 1/f fluctuation in alpha
      wave) before and after mastication were similar to the results of VAS value.
      CONCLUSIONS: Denture tolerance with different design of upper major connector
      influenced the higher center of the brain and suggested that the possibility of
      detecting changes might be indicated electroencephalographically.

PMID- 15961919
TI  - [Study on color stability of composite resins for a facing crown polymerized with
      high output photo-curing unit].
AB  - PURPOSE: This study investigated the color stability of composite resins for a
      facing crown cured with a high output photo-curing unit (Hyper LII, YAMAHACHI
      DENTAL MFG., CO.). METHODS: Four brands of composite resins for a facing crown
      after polymerization with Hyper LII were immersed in coffee. Color measurement
      was carried out before and 1, 2, and 4 weeks after immersion, and the results
      were compared. RESULTS: 1. After immersion in coffee, the L* values decreased
      gradually, the a* values showed little change, and the b* values increased
      gradually in all resins. 2. The difference in the color difference values
      (deltaE*ab) between each material became greater with time; the deltaE*ab after 4
      weeks immersion were from 3.0 [Dentacolor (DEC), dentin specimen] to 6.3 [Solidex
      (SOL), enamel specimen] on polished surfaces, and from 0.9 [Gradia (GRA), dentin
      specimen] to 5.2 (SOL, enamel specimen) on non-polished surfaces. However, the
      deltaE*ab were 1/3 to 1/5 better than those of our previous studies. 3. The
      enamel specimens showed larger color differences than the dentin specimens. 4.
      When polished surfaces were compared with non-polished surfaces, Cesead II
      (CEII), DEC and SOL showed almost equal color differences while GRA showed larger
      color differences. CONCLUSIONS: This study suggests that composite resins for a
      facing crown cured with a high output photo-curing unit result in a decrease of
      color changes with time and an improvement of color stability.

PMID- 15961920
TI  - [A case of burning mouth associated with dental metal allergy].
AB  - PATIENT: A 70-year-old male presented with a history or chief complaint of
      burning and prickly sensation in the oral cavity at two years after dental
      treatments. We diagnosed that this symptom might be due to hypersensitivity
      reaction to the Zn, Co and Hg used in dental prostheses based on the results of
      patch testing and metal analysis. After removal of all the suspected metals, the
      symptom disappeared. DISCUSSION: Many alternative causes have been proposed for
      burning mouth. As reported previously, mucosal allergic reactions have developed
      into burning mouth in patients. It is advisable to perform patch tests in
      selected patients to identify a possible etiological agent. Although patch
      testing for these symptoms might provide useful information, it is difficult to
      characterize the significance of contact allergy. Therefore, careful diagnosis,
      treatment and follow-up are necessary alleviate to symptoms of such case.
      CONCLUSION: This case showed that metal allergy might be related to the condition
      of burning mouth.

PMID- 15961921
TI  - [A case report of a speech disturbance patient treated by a magnetic attachment
      overdenture].
AB  - PATIENT: A 50-year-old female who wore a cast-clasp-supported removable partial
      denture (RPD) complained of speech disturbance, because the clasps disturbed her
      tongue movement during speech. She wished to receive dental implant treatment,
      but it was difficult to solve the esthetic problem by the planned implant
      supported fixed partial denture. Therefore, the RPD (overdenture) supported by
      magnetic attachments was inserted to recover the speech disturbance. DISCUSSION:
      The treatment outcome of this patient was evaluated with a self-administered
      questionnaire. The results suggested that the RPD with magnetic attachments
      improved the patient's pronunciation, esthetics and quality of life. CONCLUSION:
      It was suggested that the magnetic attachment overdenture effectively solved the
      speech disturbance.

PMID- 15961922
TI  - [Effect of obturator prosthesis for partial maxillectomy].
AB  - PATIENT: 77-year-old completely edentulous female was treated for a malignant
      carcinoma with an upper left posterior maxilla resection. Existing complete
      dentures were modified by an immediate surgical obturator with resin. A
      definitive obturator was fabricated following healing of the site to recover
      speech and chewing function. DISCUSSION: Thermoplastic wax was used for border
      molding of the custom tray and conventional impression procedures were followed.
      A buccal flange type obturator was utilized to reduce weight. Flat cusped
      posterior teeth were used to reduce stress on the residual ridge and facilitate
      occlusal contact and balance of the prosthesis. CONCLUSION: The patient was
      satisfied with the recovery of chewing and pronunciation. Expected chewing
      function existed on the non-resected side. Speech and pronunciation were similar
      to the pre-operative condition with complete dentures. Prosthetic rehabilitation
      with a maxillary obturator prosthesis may provide good speech and adequate
      chewing function following partial resection of the edentulous maxilla.

PMID- 15961923
TI  - [Feasibility study on a noninvasive measurement system for boron concentration.].
AB  - The kinematics of boron compounds in vivo is crucial to fully and safely utilize
      boron neutron capture therapy. In this paper, we proposed a prompt gamma-ray
      Compton scatter camera (PG-CSC), which can evaluate the 3-D kinematics of boron
      compounds without invasion. This PG-CSC combines a Compton camera with prompt
      gamma-ray analysis. The results of its design optimization and tests using
      simulations showed that one-hour-measurement was sufficient to evaluate a 3-D
      boron concentration distribution in a rat's brain with the resolution of 1 mm in
      FWHM.

PMID- 15961924
TI  - [2D imaging simulations of a small animal PET scanner with DOI measurement: jPET
      RD.].
AB  - We present a preliminary study on the design of a high sensitivity small animal
      DOI-PET scanner: jPET-RD (for Rodents with DOI detectors), which will contribute
      to molecular imaging. The 4-layer DOI block detector for the jPET-RD that
      consists of scintillation crystals (1.4 mm x 1.4 mm x 4.5 mm) and a flat panel
      position-sensitive photomultiplier tube (52 mm x 52 mm) was previously proposed.
      In this paper, we investigate imaging performance of the jPET-RD through
      numerical simulations. The scanner has a hexagonal geometry with a small diameter
      and a large axial aperture. Therefore DOI information is expected to improve
      resolution uniformity in the whole field of view (FOV). We simulate the scanner
      for various parameters of the number of DOI channels and the crystal length.
      Simulated data are reconstructed using the maximum likelihood expectation
      maximization with accurate system modeling. The trade-off results between
      background noise and spatial resolution show that only shortening the length of
      crystal does not improve the trade-off at all, and that 4-layer DOI information
      improves uniformity of spatial resolution in the whole FOV. Excellent performance
      of the jPET-RD can be expected based on the numerical simulation results.

PMID- 15961925
TI  - [A comparison of the helmet output factors for five Gamma-Knife units.].
AB  - A radiophotoluminescent (RPL) glass rod dosimeter (GRD) and a small active volume
      p-type silicon diode detector are used for the measurement of the helmet output
      factors from five Gamma-Knife units, which include four Model B units and a Model
      C unit. The output factors for the five units measured with the GRD from 14, 8
      and 4 mm helmets relative to the 18 mm helmet are 0.984 +/- 0.003, 0.951 +/-
      0.003 and 0.884 +/- 0.006, respectively. Similarly, the corresponding output
      factors measured with the p-type silicon diode detector are 0.983 +/- 0.002,
      0.952 +/- 0.003 and 0.867 +/- 0.015, respectively. The output factors are
      corrected with the end effect for each helmet of the five units. The end effect
      time for the four Model B units ranges from 4 sec for the 18 mm helmet to 2 sec
      for the 4 mm helmet. The results for the Model C unit are within 1 sec for all
      the helmets. The output factors for the five units obtained from both detectors
      are in good agreement with the values in a recent publication and the values
      recommended by Elekta, the device manufacturer, except for that of the 4 mm
      helmet measured with the GRD. The average GRD output factor for the 4 mm helmet
      is 1.6% higher than Elekta's value, 0.870, but is in good agreement with the
      published value which was measured using small active volume detectors. The
      helmet output factors for the five Gamma-Knife units measured with the GRD agree
      within measurement deviation.

PMID- 15961926
TI  - [Polarity effects of commercial plane-parallel ionization chamber in therapeutic
      electron dosimetry-Results with C-134A ionization chamber.].
AB  - Plane-parallel ionization chambers that exhibit polar effects with low energy
      electron beams are recommended for therapeutic electron dosimetry. In this study,
      the polarity effects of a C-134A ionization chamber, a major commercially
      available plane-parallel ionization chamber in Japan, were characterized as a
      function of mean energy at various depths. Polarity effects were measured at
      representative depths along depth dose curves of nominal 4, 6, 9, 12 and 15 MeV
      electron beams, and were compared with previously reported results. Polarity
      errors for the ionization chamber studied were shown to monotonically increase
      with decreasing mean energy at a given depth and were maximal at about 1-2 MeV.
      It was also shown that polarity errors depended on the energy of the incident
      electron beam. The polarity error of the C-134A ionization chamber was larger
      than that of other previously investigated plane-parallel ionization chambers.
      Because the magnitude of polarity effects should be determined throughout the
      depth dose curve in therapeutic electron dosimetry, it is always necessary to
      measure ionization readings taken at both polarities.

PMID- 15961927
TI  - Determination of the levels of anti-thyroid-stimulating hormone receptor antibody
      with thyroid peroxidase antibody in Omani patients with Graves' disease.
AB  - OBJECTIVE: To determine the levels of anti-thyroid-stimulating hormone receptor
      antibody (TRAb) and thyroid peroxidase antibodies (TPO) in Omani patients with
      Graves' disease (GD). SUBJECTS AND METHODS: ELISA was used to measure the levels
      of TRAb and TPO in sera of 111 patients with GD, 40 patients with systemic lupus
      erythematosus (SLE) and 50 healthy normal subjects. Seventy-eight GD patients
      received iodine-131 treatment while 33 newly diagnosed patients did not receive
      any treatment. RESULTS: The levels of TRAb in the patients with GD, SLE and
      normal subjects were 7.24 9+/-0.623, 1.04+/-0.179 and 0.539+/-0.070 units/liter,
      respectively. Elevated levels of TRAb were found in 75, 5 and 2% of patients with
      GD, SLE and normal subjects, respectively. For anti-TPO antibodies, the levels
      were 713.331+/-97.905, 85.575+/-34.936 and 22.96+/-4.544 lU/ml, for patients with
      GD, SLE and normal subjects, respectively. The elevated level of anti-TPO
      antibodies were found in 72, 15 and 6% of patients with GD, SLE and normal
      subjects. Statistically significant differences in positive levels of TRAb and
      anti-TPO antibodies were found in patients with GD as compared to SLE and normal
      subjects (p<0.001). The treated GD patients had lower levels of TRAb than
      untreated, but no difference was detected in the levels of anti-TPO antibodies
      between the treated and not treated. CONCLUSION: High levels of TRAb and TPO were
      detected in Omani patients with GD. TRAb may be helpful in the diagnosis and
      monitoring the efficacy of iodine-131 treatment in GD patients.

PMID- 15961928
TI  - Angiotensin-converting enzyme I/D polymorphism in Behcet's disease.
AB  - OBJECTIVE: To investigate a potential relationship between I/D polymorphism
      within intron 16 of the angiotensin-converting enzyme (ACE) gene located on human
      chromosome 17 and Behcet's disease. MATERIALS AND METHODS: Genomic DNA was
      obtained from 35 Turkish patients diagnosed with Behcet's disease according to
      the International Study Group criteria and 150 healthy individuals. Polymerase
      chain reaction was used to detect the presence of I and D (insertion and
      deletion) alleles in intron 16 of the ACE gene in these DNA samples. RESULTS: We
      found differences in ACE I/D polymorphism between Behcet's disease and healthy
      controls (chi2=4.61, d.f.=1, p=0.044). In Behcet's disease patients, the D allele
      frequency was 84.3% and I allele frequency 15.7%. CONCLUSION: An association
      between Behcet's disease and ACE polymorphism may provide a useful basis for
      future molecular studies and therapeutic approaches in this complex disease.

PMID- 15961929
TI  - Post-test probability for pulmonary embolism after ventilation-perfusion scan
      assessed by nuclear medicine physicians.
AB  - OBJECTIVE: The objective of this prospective study was to compare assessments of
      pre- and post-ventilation-perfusion (V/Q) scan probabilities for pulmonary
      embolism (PE) by the nuclear medicine physician and the referring physician.
      MATERIALS AND METHODS: Seventy-nine patients (41 females, 38 males, mean age 49
      years) referred for V/Q scans over a period of 6 months and suspected of PE were
      included in the study. The pre-test likelihood was determined independently by a
      consultant nuclear physician and a referring physician prior to the V/Q scan. The
      scan was performed according to a standard protocol using 8 view technetium-99m
      diethylenetriamine pentaacetic acid aerosol ventilation study followed by a
      technetium-99m macroaggregated albumin perfusion study. The scan was interpreted
      according to prospective investigation of pulmonary embolism diagnosis criteria.
      The post-scan probability was calculated. The probability of PE was quoted as
      low, intermediate and high. Agreement or disagreement in assessing the pre- and
      post-scan probability was classified according to the degree of difference (no
      difference: 0; minor difference: 1, and major difference: 2 grades). RESULTS: The
      agreement between the nuclear medicine and referring physicians on clinical
      probability of PE was moderate (63%) before the scan and good (90%) after the
      scan. The disagreement in assessing the clinical probability between the
      referring physician and the nuclear medicine physician was predominantly minor.
      Only 5 and 1% of the disagreement was major in pre-scan and post-scan
      probabilities, respectively. CONCLUSION: The data show that nuclear medicine
      physicians can use the assessment of pre-scan clinical likelihood to determine
      the post-scan probability of PE.

PMID- 15961930
TI  - Dysregulation of non-heme iron metabolism in glial brain tumors.
AB  - OBJECTIVE: To study iron exchange irregularities in experimental animals and
      patients with glial brain tumors to ascertain the role of the 'iron component' in
      glial brain tumor pathogenesis. SUBJECT AND METHODS: A suspension of A.101.08
      tumor cells was implanted in the cortex of the left-brain hemisphere of rats to
      model experimentally induced glial brain tumor. At 7 or 14 days after
      implantation, blood and tissue samples from the tumor, peritumoral tissue, and
      brain regions were taken for analysis. Blood and plasma samples were obtained
      from 23 patients as well as biopsy samples taken during tumor removal surgery.
      Electron resonance spectroscopy was used to determine the concentrations of
      transferrin iron, transferrin in whole blood and in blood cells, and chelatable
      and stored iron in the tissues of experimental animals and patients. RESULTS:
      Hypoferremia was found in rats with both small and large glial brain tumors,
      whereas hyperferremia was found to be a characteristic of malignant glial brain
      tumors in humans. We identified statistically significant increases in stored and
      chelatable iron concentrations in the tumor and peritumoral brain tissue compared
      to the blood and the adjacent brain tissue (probably normal) in both human
      malignant glial brain tumors and in rat experimental glial brain tumors.
      CONCLUSIONS: These findings suggest that iron misregulation plays a part in glial
      brain tumor pathogenesis and this may provide a basis for understanding the
      association between glial brain tumors and epilepsy.

PMID- 15961931
TI  - Frequency of red blood cell alloantibody in Kuwaiti population.
AB  - OBJECTIVE: The aim of this study was to analyze the alloimmunization against red
      blood cells (RBC) among Kuwaiti population. MATERIALS AND METHODS: Retrospective
      analysis of RBC alloimmunization among 179,045 Kuwaiti patients, pregnant women,
      and allogeneic blood donors was conducted for the period of 1992-2001. The
      frequency of 24 alloantibody specificities from 1,278 alloimmunized Kuwaitis was
      estimated. RESULTS: The prevalence of positive antibody screen in Kuwait was
      0.49%. The five most frequently identified alloantibodies were anti-D (27.3%),
      anti-E (18.5%), anti-K (15.6%), anti-Le(a) (8.7%), and anti-Le(b) (6.6%).
      Frequency of alloimmunization was greater among Kuwaiti female than male patients
      (3.2 F to 1 M). Anti-D (p<0.001), anti-E (p=0.05), anti-K (p=0.04) were also more
      frequently identified alloantibody among Kuwaiti females. CONCLUSION: The results
      show higher predominance of RBC alloimmunization in females than males. Anti-D,
      anti-E, and anti-K were the most common clinically significant alloantibodies
      identified in the Kuwaiti population and were also more frequent among Kuwaiti
      females.

PMID- 15961932
TI  - Significance of atypical pathogens among community-acquired pneumonia adult
      patients admitted to hospital in Kuwait.
AB  - OBJECTIVES: The aim of this study is to determine the microbial etiology and
      severity of community-acquired pneumonia (CAP) in Kuwait. SUBJECTS AND METHODS:
      The severity of consecutive adult CAP cases admitted to 3 hospitals over a 1-year
      period was classified according to the Pneumonia Outcome Research Team (PORT)
      severity index. The microbial etiology was determined using standard methods for
      bacteria and serological tests for atypical and viral pathogens. RESULTS: The
      study population was 124 of the 135 admissions; 63 female, 61 male; mean age
      41.3+/-18 years. The severity class distribution was: class I 31%, class II 37%,
      class III 17%, class IV 13%, and class V 2%. Etiological agents were identified
      from 44 patients (35%), with one pathogen in 31 (25%), two in 9 (7%), and three
      or more in 4 (3%). The most common pathogens identified were: Mycoplasma
      pneumoniae in 14 patients (11%), Legionella pneumophila in 10 (8%), Chlamydia
      pneumoniae in 8 (6%), influenza B virus in 8 (6%), influenza A virus in 5 (4%),
      Haemophilus influenzae in 4 (3%), Streptococcus pneumoniae in 3 (2%),
      Staphylococcus aureus in 3 (2%), gram-negative enterobacteria in 5 (4%),
      Moraxellacatarrhalis in 2 (2%), and viruses in 4 (3%). The yields from laboratory
      tests were 48% for paired serology, 20% from adequate sputum sample, and 3% from
      blood culture. CONCLUSION: Our study shows that a large percentage of mild CAP
      cases are admitted to hospitals in Kuwait. Atypical pathogens have a significant
      role in the etiology of CAP. There is overtreatment of CAP with a combination
      treatment consisting mainly of third-generation chephalosporins and macrolides.

PMID- 15961933
TI  - Comparison of erythrocyte sedimentation rate measurement by the automated
      SEDIsystem and conventional Westergren method using the Bland and Altman
      statistical method.
AB  - OBJECTIVES: To compare the performance of SEDIsystem(TM), a fully automated
      analyzer for the measurement of the erythrocyte sedimentation rate (ESR), with
      the manual Westergren method. MATERIALS AND METHODS: Both methods were applied to
      150 randomly selected subjects. The linear regression and Bland and Altman data
      analysis methods were used to measure the agreement between the automated and
      manual methods. RESULTS: The regression analysis showed a good correlation
      between the two methods (r=0.91). The Bland and Altman data analysis showed no
      systematic bias (95% confidence interval for mean difference); however, limits of
      agreement were between 11.52 and -37.88. This indicates that ESR values measured
      by the SEDIsystem may be 11.52 mm/h above or 37.88 mm/h below the reference
      method. A greater scatter of data was also observed with abnormally high (>25
      mm/h) ESR results (mean of difference=-21.4 and limits of agreement=-45.2 and
      2.26) compared with normal (<25 mm/h) readings (mean of difference=-3.9 and
      limits of agreement=-13.5 and 5.7). CONCLUSION: The Bland and Altman statistical
      analysis showed a wide degree of scatter between results obtained by the two ESR
      techniques that was not clearly demonstrated using the linear regression
      analysis. The automated system was found to underestimate ESR with the Bland and
      Altman statistical analysis, and therefore a correction factor is recommended.

PMID- 15961934
TI  - The use of locked nails in the treatment of humeral shaft: delayed union and
      nonunion.
AB  - OBJECTIVES: To assess the results and clinical outcome of delayed union and
      nonunion humeral shaft treatment using locked medullary nails. SUBJECTS AND
      METHODS: The Russel and Taylor humeral locking nail was used to treat 21 patients
      with humeral shaft fractures at Al Razi hospital, Kuwait, from 1997 to 2001. Of
      these, 8 had delayed union and 13 nonunion. Also, 13 had previous operative
      treatment, while 8 had nonoperative treatment. Antegrade nailing was done in all
      cases, and all nails were fixed statically. Autogenous iliac bone grafts were
      used in 17 cases. RESULTS: Of the 21 cases of fractures, 19 were united. Only 2
      cases had persistent nonunion. Eighteen cases had satisfactory shoulder function,
      and 3 lost shoulder abduction between 40 and 65 degrees. CONCLUSION: Our data
      showed that humeral locked nails can achieve satisfactory clinical results in
      treating humeral shaft delayed unions and nonunions.

PMID- 15961935
TI  - Evaluation of the BD Phoenix Automated Microbiology System for identification and
      antimicrobial susceptibility testing of common clinical isolates.
AB  - OBJECTIVE: To evaluate the accuracy and reliability of the BD Phoenix Automated
      Microbiology System for identification (ID) and antimicrobial susceptibility
      testing (AST) of Gram-positive and Gram-negative isolates. MATERIALS AND METHODS:
      The ID of 291 Gram-negative and 158 Gram-positive clinical isolates were
      evaluated by the system. The AST of 252 Gram-negative and 151 Gram-positive
      isolates with correct ID were then evaluated. The results were compared with
      those of the API ID system and the microbroth dilution method. All discrepant
      results were repeated for verification. RESULTS: Over 90% Gram-negative and Gram
      positive isolates were correctly identified to species or genus level by the
      Phoenix system. The minimum inhibitory concentration agreement rates between the
      Phoenix and the microbroth dilution methods within +/-1 dilution ranged from 87.3
      to 97.6% for Gram-negative isolates, and from 50 to 100% for Gram-positive
      isolates. For Gram-positive isolates, vancomycin had significant low minimum
      inhibitory concentration agreement rates. CONCLUSIONS: Overall, the results
      indicate that the Phoenix system is a reliable system. It could provide accurate
      ID and AST results for routine clinical laboratories.

PMID- 15961936
TI  - Cementless Zweymuller hip replacement: a short-term follow-up in Al Razi
      Hospital, Kuwait.
AB  - OBJECTIVE: To present initial experience of the first 71 cases of cementless
      total hip replacement in Al Razi Hospital. SUBJECT AND METHODS: Between 1996 and
      2004, total hip replacement was performed in 71 patients (40 male, 31 female,
      average age 40.7 years, range 17-74) using Zweymuller cementless prosthesis. The
      patients were followed clinically and radiologically over an average period of 36
      months (range 6-84). The results were assessed according to Merle d'Aubigne
      clinical score. Radiological assessment included position of the implant,
      behavior of the prosthesis/bone interface and signs of osteointegration. RESULTS:
      Average clinical score during the 3 years' follow-up period was 17.8 points. Most
      of the implants were in optimal positions. No significant radiological
      modifications of the implant-bone interface were observed. CONCLUSION: Zweymuller
      total hip prosthesis gives excellent clinical and radiological results in short
      term follow-up.

PMID- 15961937
TI  - Antibiotic susceptibility profile of group B streptococcus (Streptococcus
      agalactiae) at the Maternity Hospital, Kuwait.
AB  - OBJECTIVES: This study was designed to determine the antibiotic susceptibility
      profile of clinical isolates of group B streptococcus(GBS, Streptococcus
      agalactiae) and to use the information for formulating appropriate intrapartum
      antibiotic policy for GBS carriage in pregnancy. MATERIALS AND METHODS: A total
      of 1,166 clinical isolates (single isolates) of GBS obtained from vaginal/rectal
      samples of pregnant mothers seen at the Maternity Hospital, Kuwait were studied
      over a period of 43 months between May 1998 and December 2001. The isolates were
      identified by standard methods and their susceptibility to penicillin,
      ampicillin, cephalothin, clindamycin and erythromycin was determined by disk
      diffusion technique, minimal inhibitory concentration (MIC) using the Vitek
      automated sensitivity card system and E-test methods. RESULTS: All the GBS
      isolates were fully susceptible to penicillin, ampicillin and cephalothin. Only
      0.7 and 1.7% were resistant to erythromycin and clindamycin, respectively. Disk
      diffusion results interpreted by the standard interpretative criteria recommended
      by the National Committee on Clinical Laboratory Standards correlated well with
      Vitek results as well as the E-test for penicillin. The MIC of penicillin against
      all isolates ranged between 0.016 and 0.064 microg/ml. For the 6 months of 1998
      and throughout 1999, the percentages of isolates susceptible at MICs of 0.016,
      0.023, 0.032, 0.047 and 0.064 microg/ml were 6.5, 9.9, 31, 38.8 and 12%,
      respectively. The trend was similar in the subsequent years except that the
      percentage of isolates susceptible at MIC of 0.064 microg/ml increased to 26.6%
      in 2000, but went down to 4.4% in 2001. CONCLUSION: The trend in susceptibility
      of GBS to a variety of often used antibiotics for therapy and prophylaxis
      remained unchanged over nearly a 4-year period. The apparent increase in the
      number of isolates susceptible at higher MIC values of penicillin (0.047 and
      0.064 microg/ml) in 2000 appears to be a bleb that cannot be explained by any
      event in the hospital for that year. Our data, based on susceptibility profiles,
      supports the use of penicillin or ampicillin for intrapartum chemoprophylaxis to
      prevent early-onset neonatal GBS infections.

PMID- 15961938
TI  - E-test: an alternative method for susceptibility testing of Mycobacterium
      tuberculosis.
AB  - OBJECTIVE: The purpose of this study was to compare the agar proportion method
      with the E-test method for susceptibility testing of Mycobacterium tuberculosis.
      MATERIALS AND METHODS: A total of 100 isolates were tested for isoniazid,
      rifampin, streptomycin and ethambutol susceptibility using an indirect-proportion
      method as well as the E-test method. RESULTS: Categorical agreement between the
      methods was 100% for isoniazid, rifampin, streptomycin, and ethambutol.
      CONCLUSION: The E-test method appears to be an alternative method to agar
      proportion for testing the susceptibility of M. tuberculosis isolates to the
      first-line antituberculous agents.

PMID- 15961939
TI  - Investigation of Epstein-Barr virus DNA in formalin-fixed and paraffin- embedded
      breast cancer tissues.
AB  - OBJECTIVE: To investigate etiological role of Epstein-Barr virus (EBV) DNA in
      breast cancer. MATERIALS AND METHODS: The presence of EBV DNA in 57 breast cancer
      tissues was investigated with a sensitive PCR assay. The breast cancer tissues
      were from invasive ductular (n=28), lobular (n=20) and other miscellaneous
      carcinomas (n=9). Tissues from normal breasts and patients with various benign
      breast diseases (n=55): fibrocystic disease (n=34), fibroadenoma (n=16),
      hyperplasia, and granulomatous mastitis (n=5), were used as control samples.
      RESULTS: EBV DNA was detected in 13 (23%) cancerous tissues (7 ductular, 4
      lobular, 2 other carcinoma) and 19 (35%) in the control tissues. The difference
      between EBV presence in malignant and benign tissues was not statistically
      significant (p>0.05). CONCLUSION: The presence of EBV DNA was detected almost
      equally in both breast cancer and normal tissues, which indicates no etiological
      role for EBV in breast cancer. We suggest further etiological studies.

PMID- 15961940
TI  - Transurethral microwave thermotherapy for treatment of benign prostatic
      hyperplasia: a preliminary assessment of the Prostalund feedback treatment
      machine.
AB  - OBJECTIVE: The aim of this preliminary study was to evaluate the efficacy of
      Prostalund feedback treatment (PLFT) using microwave thermotherapy equipment for
      benign prostate hyperplasia (BPH) in patients with urinary retention and an
      indwelling urethral catheter. SUBJECTS AND METHODS: Four unselected patients, 51
      68 years old (mean age 60 years), with urinary retention and an indwelling
      catheter were treated with PLFT under local anaesthesia and sedation. They were
      considered high-risk patients for treatment by transurethral resection of the
      prostate (TURP) under spinal or general anaesthesia. Initial assessment included
      prostate-specific antigen, determination of prostate volume and exclusion of
      prostate cancer using transrectal ultrasound (TRUS). The patients had the
      indwelling catheter for 1-2 weeks prior to treatment, the urethral catheters were
      removed 10-12 days after PLFT. Two patients who failed to void after
      transurethral microwave thermotherapy underwent urodynamic study to determine the
      reason for failure. RESULT: The mean volume of the treated prostate gland was
      75.50 cm3 (range 51-150 cm3). Two of the 4 patients were successfully relieved of
      their indwelling catheter with satisfactory peak flow, residual urine and symptom
      score, while treatment failed in the remaining 2. The reasons for the failure
      were identified as a small bladder capacity and neurogenic bladder in a diabetic
      patient and the presence of a middle lobe with large protruding lateral lobes
      into the bladder of the other patient. The latter patient had a prostate volume
      of 150 cm3. 'Salvage' TURP in both patients revealed that PLFT caused extensive
      necrosis of prostatic tissue and the TURP was then accomplished with minimal
      blood loss (<200 ml) even in the patient with 150-gram prostate. There were no
      serious complications such as bleeding, sepsis, rectoprostatic fistula or urine
      incontinence. CONCLUSION: The result of this preliminary investigation appears to
      be satisfactory and indicates that PLFT could be a good, minimally invasive
      alternative to surgery for BPH patients with retention of urine and an indwelling
      catheter.

PMID- 15961941
TI  - Atraumatic restorative treatment with resin-modified glass ionomer material:
      short-term results of a pilot study.
AB  - OBJECTIVES: The aim of this study was to assess the feasibility of the resin
      modified glass ionomer (RMGI) material in atraumatic restorative treatment (ART)
      approach and compare RMGI with the high-strength traditional glass ionomer cement
      (GIC) in permanent teeth with one or more surface-carious cavities. MATERIALS AND
      METHODS: This study was conducted in a village school in rural southeastern
      Anatolia, Turkey. The RMGI and GIC restorations with the ART technique were
      placed randomly employing a split mouth design. In addition, the ART approach was
      used when necessary for both primary and/or permanent teeth with no pulpal
      involvement and no perceived pain before treatment. Ninety-one fillings were
      placed on contralateral molar pairs of 37 children. Baseline and 6-month
      evaluation of the fillings were made with the classic ART, modified Ryge and
      USPHS criteria. RESULTS: Based on the ART criteria, 100% of RMGI and 92.4% of GIC
      restorations were classified as successful after 6 months, and the difference
      between the 2 groups was statistically significant (p=0.009). While marginal
      discoloration was the commonest failure in the RMGI group according to both the
      modified Ryge and USPHS criteria, unsatisfactory surface texture and low anatomic
      form were the commonly seen failures in the ART technique. CONCLUSION: Generally,
      for each rating system, RMGI exhibited better clinical performance than GIC in
      all categories, except for marginal discoloration. Results based on the 6-month
      evaluation show that RMGI can be an alternative material to the GIC.

PMID- 15961942
TI  - Late development of diabetes mellitus after interferon-alfa and ribavirin therapy
      for chronic hepatitis C: a case report.
AB  - OBJECTIVE: To report the late development of immune-mediated diabetes mellitus
      after completion of alfa-interferon therapy for hepatitis C in an Asian patient.
      CLINICAL PRESENTATION AND INTERVENTION: A 50-year-old male with chronic hepatitis
      C received treatment with alfa-interferon and ribavirin for 52 weeks. He
      developed immune-mediated diabetes mellitus with low C-peptide and positive
      antiglutamic acid decarboxylase antibody after completion of therapy. The
      hepatitis C infection was eradicated, but he continued to be diabetic requiring
      insulin therapy during the follow-up. CONCLUSION: This report shows thatimmune
      mediateddiabetes mellitus can occur as a late complication of alfa-interferon
      therapy.

PMID- 15961943
TI  - Large adrenal pseudocyst presenting with epigastric distress and abdominal
      distention.
AB  - OBJECTIVE: We report a patient with a large adrenal pseudocyst presenting with
      epigastric distress and abdominal distention. CLINICAL PRESENTATION AND
      INTERVENTION: A 35-year-old man presented with a 1-year history of nonspecific
      epigastric distress and abdominal distention. Routine laboratory tests and
      endocrine function tests were within the normal ranges. Magnetic resonance
      imaging (MRI) revealed a large left adrenal cyst. Adrenal cyst showed low
      intensity on T1-weighted MRI images and high density on T2-weighted MRI images.
      The patient underwent surgery, and the cyst was completely removed. Histological
      examination showed that the cyst wall consisted of hyalinized fibrous tissue
      without an epithelial or endothelial lining, and a diagnosis of an adrenal
      pseudocyst was made. Symptoms resolved after pseudocyst removal. CONCLUSION: The
      report showed a patient with adrenal pseudocyst, a rare and uncommon condition
      that was diagnosed on MR images and confirmed by histology. The epigastric
      distress and the abdominal distention resolved after the pseudocyst was
      surgically removed.

PMID- 15961944
TI  - Primary hepatic carcinoid tumor.
AB  - OBJECTIVES: To describe a rare case of primary carcinoid tumor of the liver and
      its management. CLINICAL PRESENTATION AND INTERVENTIONS: A 44-year-old Nigerian
      male presented with a big inoperable liver mass, which proved to be a carcinoid
      tumor by fine needle aspiration cytology. Extensive search for a primary lesion
      including laparotomy and peroperative ultrasound failed to find a primary lesion
      in the gastrointestinal tract and pancreas. Percutaneous embolization of the
      tumor followed by complete dearterializations of the liver seemed to have halted
      the growth of the tumor. The patient remained well with normal liver function
      tests for 56 months when he decided to go back to his country. CONCLUSION: The
      result showed that dearterializations of a primary inoperable carcinoid of the
      liver offered good palliation.

PMID- 15961945
TI  - Preliminary evidence for ethnic differences in primary hyperoxaluria type 1
      genotype.
AB  - BACKGROUND: Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of
      peroxisomal alanine:glyoxylate aminotransferase (AGT). In about one third of
      patients, enzymatically active AGT is synthesized but is mistargeted to
      mitochondria. There are more than 50 mutations identified in the gene for AGT.
      Four mutations, G170R, 33_34insC, F152I and I244T account for more than 50% of
      PH1 alleles. The question arose whether there are ethnic differences in PH1
      genotype. METHODS: The published data on mutations in the AGT gene were examined
      with respect to recurrences and geographic or ethnic association. The mutations
      that have been found in at least 2 unrelated individuals were considered.
      RESULTS: Two common mutations, G170R and 33_34insC showed no obvious ethnic
      associations and have been found in a variety of populations. A third common PH1
      mutation, I244T, has a strong association with people from a Spanish or North
      African background. A particularly high frequency among Canary Islands PH1
      patients suggests a probable founder effect. Between these two extremes are a
      number of mutations that recur at low frequency within certain ethnic groups.
      CONCLUSIONS: Ethnic associations of PH1 genotypes span a spectrum ranging from
      limited recurrences confined to a population group, to a probable founder effect.

PMID- 15961946
TI  - Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation
      in primary hyperoxaluria type 1 in Israel.
AB  - BACKGROUND/AIMS: Primary hyperoxaluria type 1 (PH1) is caused by the deficiency
      of the liver enzyme alanine:glyoxylate aminotransferase which results in
      increased synthesis and excretion of oxalate. The clinical manifestations of PH1
      are heterogeneous with respect to the age of onset and rate of progression. The
      aim of this study was to investigate possible relationships between a given
      genotype, the biochemical profile and the clinical phenotype. METHODS: We
      conducted a study of 56 patients from 22 families with PH1 from Israel. The
      clinical and biochemical data were compiled and the genotype was determined for
      each family. RESULTS: The prevalent phenotype was of early onset with progression
      to end-stage renal disease during the first decade of life. Fifteen PH1-causing
      mutations were detected in 21 families: 10 were first described in this patient
      population. Marked intra-familial clinical heterogeneity was noted, meaning that
      there was no correlation between a given genotype and the phenotype. CONCLUSIONS:
      The clinical course of patients with PH1 is not dictated primarily by its
      genotype. Other genetic and/or environmental factors play a role in determining
      the ultimate phenotype.

PMID- 15961947
TI  - Primary hyperoxaluria--the German experience.
AB  - BACKGROUND: Primary hyperoxaluria (PH) is a heterogeneous disease with variable
      age of onset and inconsistent progression into renal failure (ESRF). AIMS: In
      1994 we initiated a survey within our Pediatric Nephrology working group to
      ascertain epidemiologic data and current practices. Updates were performed in
      2000 and 2004. RESULTS: Diagnosis of PH was made in 65 patients (42 with PH type
      I, 3 with PH type II, 12 unclassified and 8 reported dead), which suggests a
      minimum prevalence of 0.7 per 1 million of the population. First symptoms were
      urolithiasis, nephrocalcinosis, urinary tract infection or hematuria. Diagnosis
      was often delayed and was made only in ESRF in 11% of patients. Measurement of
      urine metabolites or plasma oxalate in ESRF was performed in 76 and 57%,
      respectively. Determination of enzyme activity in liver biopsy (55% overall) and
      mutation analysis have increasingly been performed since 2000 (84.2 and 51%).
      Treatment included high fluid intake, pyridoxine, citrate and magnesium
      preparations. Pyridoxine response was reported in 21% of patients. No
      genotype/phenotype correlation was seen. Most patients (39) do not require renal
      replacement therapy, 5 patients receive chronic hemodialysis. Preemptive liver (n
      = 5) and combined liver-kidney transplantation (n = 9) were the preferred
      transplantation procedures. CONCLUSION: Despite increasing knowledge and
      awareness, diagnosis of PH is still too often delayed and diagnosis only made in
      ESRF. Most German patients, however, do currently not require renal replacement
      therapy. Genotype/phenotype correlations were not found. Combined liver kidney
      transplantation is the preferred procedure, but has its specific risks.
      Additional treatment options are clearly needed.

PMID- 15961948
TI  - A 20-year experience of combined liver/kidney transplantation for primary
      hyperoxaluria (PH1): the European PH1 transplant registry experience 1984-2004.
AB  - Primary hyperoxaluria (PH1) is a condition caused by a hepatic-based enzyme
      defect which can lead to renal failure due to oxalate stone disease, obstructive
      uropathy and nephrocalcinosis. It has been shown that the underlying metabolic
      defect can be corrected by liver transplantation and in most cases (renal failure
      having already occurred) is accompanied by a kidney graft. This paper describes
      the current results of 127 liver transplants performed in 117 patients over a 20
      year period from 1984 to 2004 in 35 European centres. The mean age at onset of
      symptoms was 5.6 +/- 7.8 years and the mean age at which a diagnosis was made was
      8.8 +/- 9.5 years. The diagnosis was confirmed by liver biopsy proven decreased
      AGT activity in 68% of cases, hyperoxaluria in 74%, hyperglycolicaciduria in 37%
      and hyperoxalaemia in 50%. Patients were transplanted at a mean age of 16.5 +/-
      11.4 years following a period of dialysis of 3.2 +/- 3.2 years (range 0-14.4
      years). 1-, 5- and 10-year patient survival values were 86, 80 and 69%,
      respectively, and liver graft survival rates of 80, 72 and 60% at the same time
      intervals. There have been 27 deaths and 10 liver retransplants have been carried
      out. Patient outcomes are improved when prolonged periods on dialysis and the
      complications of systemic oxalosis have not occurred.

PMID- 15961949
TI  - International registry for primary hyperoxaluria.
AB  - BACKGROUND/AIMS: Primary hyperoxaluria (PH) is an inherited disorder that causes
      calcium urolithiasis and renal failure. Due to its rarity, experience at most
      centers with this disease is limited. METHODS: A secure, web-based, institutional
      review board/ethics committee and American Health Insurance Portability and
      Accountability Act (HIPAA)-compliant registry was developed to facilitate
      international contributions to a data base. To date 95 PH patients have been
      entered. RESULTS: PH type was confirmed in 84/95 (PH1 79%, PH2 9%). Mean age +/-
      SD at symptom onset was 9.5 +/- 10.2 (median 5.5) years whereas age at diagnosis
      was 15.0 +/- 15.2 (median 10.0) years. Urolithiasis was present at diagnosis in
      90% (mean 7, median 1, stones prior to diagnosis) and nephrocalcinosis in 48%.
      Surprisingly 15% of the patients were asymptomatic at the time of diagnosis.
      Nineteen of the 95 patients were first recognized to have PH after they had
      reached end-stage renal disease, with the diagnosis made only after kidney
      transplantation in 7 patients. Patients were followed for 12.1 +/- 10.6 (median
      9.4) years. Thirty-four of 95 progressed to end-stage renal failure, before (19
      patients) or after (15 patients) diagnosis. In the PH1 cohort actuarial renal
      survival was 64% at 30 years of age, 47% at 40 years, and 29% at 50 years.
      CONCLUSION: We have developed a PH registry, and demonstrated the feasibility of
      this secure, web-based approach for data entry. By facilitating accumulation of
      an increasing cohort of patients, this registry should allow more complete
      characterization of clinical expression of PH, an appreciation of geographic
      variability, and identification of treatment outcomes.

PMID- 15961950
TI  - Primary hyperoxaluria type 1 in Japan.
AB  - BACKGROUND/AIMS: Current status of primary hyperoxaluria (PH) has not been
      surveyed in Japan. METHODS: Japanese patients with PH were reviewed in the
      published literature. RESULTS: Fifty-nine patients were diagnosed as PH from 1962
      to 2003. The median ages both at diagnosis and at the onset of initial symptoms
      were 17 (range: 0.02-63) and 13 (range: 0-58) years, respectively. Twenty-nine
      (49%) patients were older than 20 years at diagnosis, among whom 26 (90%) already
      presented end-stage renal failure (ESRF) or soon evolved into ESRF. Among 30
      (51%) diagnosed as PH under 20 years old, only 13 (43%) were already in a
      terminal stage of renal insufficiency. Ten patients were diagnosed as PH1 by
      liver biopsy. We identified two types of enzymatic phenotypes in 3 of those
      patients examined. In 1 case, immunoreactive SPT/AGT protein level was very low
      due to accelerated proteolysis, while in other 2 cases, the immunoreactivity was
      detected on mitochondria due to mistargeting. Of 9 cases having been subjected to
      kidney transplantation at a median age of 20 years (range 7.3-40.0), it was only
      2 cases that were reported to be successful, while the median survival time of
      the kidney grafts being 1.4 years (range 0-7). Of 4 patients having undergone
      combined liver/kidney transplantations (at the ages of 1.3, 1.4, 9 and 41 years,
      respectively), the surgery was successful in 3 cases; in the remaining one case,
      however, rejection required removal of the transplanted kidney was observed. The
      overall survival ratio of all the 59 PH cases accounted for 77, 71 and 55% at 5,
      10 and 20 years, respectively. CONCLUSION: Assuming that the majority of the 59
      patients with PH reported was classified as PH1, it is postulated that morbidity
      of violent infantile PH1 in Japan might be less than those in the USA and Europe,
      and symptoms of elderly Japanese PH1 patients seem to be milder than those of
      Western patients. Establishment of an early detection system of PH1 and more
      popular application of combined liver/kidney transplantation deserve further
      study.

PMID- 15961951
TI  - Molecular etiology of primary hyperoxaluria type 1: new directions for treatment.
AB  - Primary hyperoxaluria type 1 (PH1) is a rare autosomal-recessive disorder caused
      by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase
      (AGT). AGT deficiency results in increased synthesis and excretion of the
      metabolic end-product oxalate and deposition of insoluble calcium oxalate in the
      kidney and urinary tract. Classic treatments for PH1 have tended to address the
      more distal aspects of the disease process (i.e. the symptoms rather than the
      causes). However, advances in the understanding of the molecular etiology of PH1
      over the past decade have shifted attention towards the more proximal aspects of
      the disease process (i.e. the causes rather than the symptoms). The determination
      of the crystal structure of AGT has enabled the effects of some of the most
      important missense mutations in the AGXT gene to be rationalised in terms of AGT
      folding, dimerization and stability. This has opened up new possibilities for the
      design pharmacological agents that might counteract the destabilizing effects of
      these mutations and which might be of use for the treatment of a potentially life
      threatening and difficult-to-treat disease.

PMID- 15961952
TI  - Early prediction of acute renal injury using urinary proteomics.
AB  - AIMS: The lack of early biomarkers for acute renal failure (ARF) has crippled our
      ability to launch potentially effective therapeutic measures. We tested the
      hypothesis that urinary proteomics could identify novel early biomarker patterns
      for ischemic renal injury. METHODS: Sixty patients undergoing cardiopulmonary
      bypass (CPB) were enrolled. Urine samples obtained at 2 and 6 h post CPB were
      analyzed by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass
      Spectrometry (SELDI-TOF-MS). The primary outcome variable was ARF, defined as a
      50% or greater increase in serum creatinine. RESULTS: Fifteen patients (25%)
      developed ARF 2-3 days after CPB. SELDI-TOF-MS analysis of urine from the ARF
      group at baseline versus at 2 and 6 h post-CPB consistently showed a marked and
      statistically significant enhancement of protein biomarkers with m/z of 6.4,
      28.5, 43 and 66 kDa. The same biomarkers were enhanced when comparing control
      versus ARF groups at 2 and 6 h post-CPB. The sensitivity and specificity of the
      28.5-, 43- and 66-kDa biomarkers for the prediction of ARF at 2 h following CPB
      was 100%. The receiver operating characteristic curves revealed an area under the
      curve of 0.98. CONCLUSION: SELDI-TOF-MS is a novel, non-invasive, sensitive,
      highly predictive, reproducible, rapid method for the prediction of acute renal
      injury following CPB.

PMID- 15961953
TI  - Hypersensitivity pneumonitis due to Bunashimeji mushrooms in the mushroom
      industry.
AB  - BACKGROUND: Detection of hypersensitivity pneumonitis (HP) in employees involved
      in the Bunashimeji mushroom industry is difficult. The level of precipitating
      antibody is not related with the prediction of progression and resolution of HP.
      The aims of this study were to examine the actual prevalence of HP in the
      Bunashimeji industry and the clinical differences among selected employees.
      METHODS: One hundred and fourteen employees worked in Bunashimeji enterprises.
      These subjects were divided into the following subgroups: office workers,
      pickers/packers with mask and pickers/packers without mask. We measured serum
      Krebs von der Lungen-6 (KL-6), surfactant protein (SP)-A and SP-D, and examined
      the stimulation index (SI) due to Bunashimeji spores. Chest high-resolution
      computed tomography (HRCT), pulmonary function tests and bronchoalveolar lavage
      (BAL) were performed for select employees who showed positive SI values (>200%)
      to examine the clinical differences. RESULTS: The proportion of respiratory
      symptoms was significantly higher in the pickers/packers than that in the office
      workers. The picker/packer group had high serum KL-6 concentrations and SI
      compared with the office worker group. Thirty select employees were divided into
      the following three subgroups: HP, select employees without HP, and SI <400% and
      KL-6 <500 U/ml , using high SI levels (>400%) and positive serum KL-6
      concentration (>500 U/ml). Four exhibited ground glass opacities with
      centrilobular fine nodules on HRCT, and 8 had high numbers of lymphocytes in the
      BAL fluid. The BAL findings and serum KL-6 concentrations showed significant
      differences among the three groups. CONCLUSIONS: Four employees were evaluated as
      having HP. Serum KL-6 and SP-D may be related to the resolution of HP in addition
      to SI and chest HRCT.

PMID- 15961954
TI  - Prevalence of allergy symptoms and total IgE in a New York City cohort and their
      association with birth order.
AB  - BACKGROUND: An inverse association between birth order and allergic disease has
      been widely observed, but has not been examined in the high asthma prevalence,
      inner-city populations of the United States. As part of an ongoing prospective
      birth cohort study, the prevalence of early phenotypes of asthma and/or allergy
      was compared with those reported in other studies, and the association with birth
      order was evaluated. METHODS: Children of Dominican and African-American mothers
      living in Northern Manhattan underwent detailed periodic questionnaires. Total
      IgE from the mothers (n = 321) and the children at birth (n = 291) and at ages 24
      (n = 244) and 36 (n = 155) months was measured. The association between birth
      order and allergy symptoms was evaluated at 12 (n = 350), 24 (n = 290) and 36 (n
      = 247) months. RESULTS: Total serum IgE was detectable (>0.5 IU/ml) in 35% of the
      children's cord blood and averaged 15 and 21 IU/ml at ages 24 and 36 months,
      respectively. They were not significantly different at any age between children
      with and without older siblings. Additionally, at these ages, there were no
      consistent associations between birth order and either wheeze, itchy eyes or
      eczema. CONCLUSIONS: Despite a substantially higher prevalence of asthma in the
      Northern Manhattan community compared with other areas, total IgE levels at ages
      24 and 36 months, but not cord blood, are similar to those reported in other
      areas of the world. In this community, results at this age do not support a
      protective effect of higher birth order.

PMID- 15961955
TI  - Effect of liver transplantation on tuftsin activity and phagocytic activity of
      neutrophil granulocytes in patients with liver cirrhosis.
AB  - BACKGROUND: Tuftsin activity (TA) is reduced in cirrhosis. This contributes to
      the defective phagocytic activity (PA) of neutrophil granulocytes and is related
      to the impairment of splenic function. Orthotopic liver transplantation (OLT)
      cures cirrhosis and might restore TA. This study was aimed at determining if OLT
      restores TA and PA. METHODS: We measured in 9 cirrhotic patients, before and
      after successful OLT, TA by a bioassay and PA by chemiluminescence in which
      neutrophils of the patient were tested with both autologous (PA1) and pooled sera
      from healthy subjects (PA2). Splenic function was assayed by the pitted red cell
      count. RESULTS: Before OLT, TA was reduced in 7 patients, and PA1 in all the
      patients. Pitted cell count was elevated in all the patients. After OLT (median
      39 months; range 21-49), TA improved in all cases [median: from 8% (5-16%) to 20%
      (9-22%), p < 0.008], normalizing in 5 out of the 7 patients with low values. PA1
      improved in all the patients [from 102 cpm (65-128 cpm) to 235 cpm (78-280 cpm),
      p < 0.008], normalizing in 5. Pitted red count decreased in 7 patients and
      normalized in 3 [from 3.3% (2.1-6.0%) to 2.4% (1.4-2.8%), p < 0.021]. Platelet
      count [from 55 x 10(3) (30-100) to 185 x 10(3) (93-286), p < 0.008] and leucocyte
      count [from 3.60 x 10(3) (1.81-5.23) to 5.53 x 10(3) (3.31-6.71), p < 0.008] also
      improved. CONCLUSIONS: OLT improves TA and PA of cirrhotic patients. This effect
      is associated with an improvement of both functional hyposplenism and
      haematological hypersplenism. The restoration of natural defences against
      infections may mitigate the adverse effect of immunosuppressive treatment.

PMID- 15961956
TI  - ACP1 genotype and asthma in the Chinese Han population.

PMID- 15961957
TI  - Differential regulation of luteinizing hormone and follicle-stimulating hormone
      expression during ovarian development and under sexual steroid feedback in the
      European eel.
AB  - Pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating
      hormone (FSH) are, in teleosts as in mammals, under the control of hypothalamic
      factors and steroid feedbacks. In teleosts, feedback regulations largely vary
      depending on species and physiological stage. In the present study the regulation
      of FSH and LH expression was investigated in the European eel, a fish of
      biological and phylogenetical interest as a representative of an early group of
      teleosts. The eel FSHbeta subunit was cloned, sequenced and together with earlier
      isolated eel LHbeta and glycoprotein hormone alpha (GPalpha) subunits used to
      study the differential regulation of LH and FSH. In situ hybridization indicated
      that FSHbeta and LHbeta are expressed by separate cells of the proximal pars
      distalis of the adenohypophysis, differently from the situation in mammals. The
      profiles of LHbeta and FSHbeta subunit expression were compared during
      experimental ovarian maturation, using dot-blot assays. Expression levels for
      LHbeta and GPalpha increased throughout ovarian development with a positive
      correlation between these two subunits. Conversely, FSHbeta mRNA levels
      decreased. To understand the role of sex steroids in these opposite variations,
      immature eels were treated with estradiol (E2)and testosterone (T), both steroids
      being produced in eel ovaries during gonadal development. E2 treatment induced
      increases in both LHbeta and GPalpha mRNA levels, without any significant effect
      on FSHbeta. In contrast, T treatment induced a decrease in FSHbeta mRNA levels,
      without any significant effect on the other subunits. These data demonstrate that
      steroids exert a differential feedback on eel gonadotropin expression, with an E2
      specific positive feedback on LH and a T-specific negative feedback on FSH,
      leading to an opposite regulation of LH and FSH during ovarian development.

PMID- 15961958
TI  - Expression of glutamate receptor subunits in the hypothalamus of the female rat
      during the afternoon of the proestrous luteinizing hormone surge and effects of
      antiprogestin treatment and aging.
AB  - The excitatory transmitter, glutamate has been implicated in the control of
      reproduction, hormone secretion and neuroendocrine regulation. The present study
      examined whether the hypothalamic expression of three key ionotropic glutamate
      receptor subunits (NMDAR1, GluR1 and GluR6) fluctuates significantly on proestrus
      in the rat, and whether treatment with the antiprogestin, RU486 affected
      glutamate receptor subunit expression. The studies revealed that NMDAR1, GluR1
      and GluR6 mRNA levels in the mediobasal hypothalamus (MBH) and preoptic area
      (POA) fluctuate little throughout the day of proestrus. However, treatment with
      the antiprogestin, RU486 induced a significant elevation of GluR6 mRNA levels at
      14.00 and 16.00 h on proestrus in the MBH, suggesting that endogenous
      progesterone (P4) may act to inhibit hypothalamic GluR6 levels. In support of
      this suggestion, exogenous P4 treatment to estrogen (E2)-primed ovariectomized
      (ovx) rats significantly suppressed GluR6 mRNA levels in the afternoon (12.00
      16.00 h) in the MBH, and at 12.00 h in the POA, which preceded LH surge
      induction. Likewise, temporal examination of hypothalamic GluR6 protein levels in
      E2 + P4-treated young and middle-aged ovx rats revealed an early elevation from
      12.00 to 14.00 h, which was followed by a fall from 16.00 to 20.00 h. The early
      elevation of GluR6 protein levels was most pronounced in the POA of the young
      rat, and this elevation was markedly attenuated in the middle-aged rat. As a
      whole, the studies suggest that glutamate receptor expression fluctuates little
      on proestrus in the hypothalamus, but that expression of the kainate GluR6
      receptor subunit may be modulated by progesterone and aging.

PMID- 15961959
TI  - Effects of D-amphetamine on temporal discrimination in pigeons.
AB  - Two experiments used a matching to sample of durations procedure to examine
      changes in temporal discrimination evoked by D-amphetamine (0.75, 1.50, 2.25 and
      3.0 mg/kg i.m.) in pigeons. Responses to one key color were reinforced after long
      (8-s) stimuli: responses to the alternative key color were reinforced after short
      (2-s) stimuli. Stimuli of intermediate duration were reinforced in Experiment 1
      and were not reinforced in Experiment 2. Sigmoid functions relating percent of
      choices of the key reinforced after long-duration stimuli to the duration of
      stimulus presented were fit by a cumulative normal function. In addition to a
      parameter giving the left/right position of the sigmoid curves (which indexes
      temporal perception), this function also provided estimates of the range and
      slope of the curve (measures of stimulus control). The results showed that,
      contrary to many published reports, amphetamine had no effect on the left/right
      positioning of the sigmoid curve. There was, however, an effect of amphetamine on
      stimulus control, as shown by the general flattening of the psychophysical
      functions. Little evidence of tolerance to the drug's behavioral effects was
      found after 30 consecutive days of behavioral testing under amphetamine.

PMID- 15961960
TI  - Antagonistic interaction between adenosine A2A and dopamine D2 receptors
      modulates the social recognition memory in reserpine-treated rats.
AB  - Increasing evidence suggests that antagonistic interactions between specific
      subtypes of adenosine and dopamine receptors in the basal ganglia are involved in
      the control of motor activity. However, there are few studies investigating this
      interaction in other brain regions and its role in additional functions. In the
      present study, we evaluated whether reserpine-treated rats (1.0 mg/kg, i.p.)
      exhibit altered social recognition memory abilities. The effects of acute
      administration of the dopamine receptor agonists 7,8-dihydroxy-1-phenyl-2,3,4,5
      tetrahydro-1H-3 benzazepine (SKF 38393, dopamine D(1) receptor agonist) and
      quinpirole (dopamine D(2) receptor agonist), together with the adenosine receptor
      antagonists caffeine (non-selective), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX,
      adenosine A(1) receptor antagonist) and 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo
      {2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, adenosine A(2A) receptor
      antagonist), were also investigated. Twenty-four hours after treatment, reserpine
      treated rats exhibited a significant disruption in the ability to recognize a
      juvenile rat after a short period of time. These animals did not show any motor
      deficit. The social recognition disruption induced by reserpine was reversed by
      acute treatment with quinpirole (0.05-0.1 mg/kg, i.p.), caffeine (10.0-30.0
      mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.), but not with SKF 38393 (0.5-3.0
      mg/kg, i.p.) or DPCPX (0.5-3.0 mg/kg, i.p.). Moreover, a synergistic response was
      observed following the co-administration of 'non-effective' doses of ZM241385
      (0.1 mg/kg, i.p.) and quinpirole (0.01 mg/kg, i.p.). These results reinforce and
      extend the notion of antagonistic interactions between adenosine and dopamine
      receptors, and demonstrate, for the first time, that the blockade of adenosine
      A(2A) receptors and the activation of dopamine D(2) receptors can reverse the
      social recognition deficits induced by reserpine in rats.

PMID- 15961961
TI  - Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.
AB  - The present study assessed the effect of D-amphetamine on responding maintained
      by wheel-running and sucrose reinforcement. Six male albino Wistar rats were
      placed in running wheels and exposed to a fixed-interval 30-s schedule that
      produced either a drop of 5% sucrose solution or the opportunity to run for 15 s
      as reinforcing consequences for lever pressing. Each reinforcer type was signaled
      by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D
      amphetamine were administered by i.p. injection 20 min prior to a session. As the
      dose increased, index of curvature values decreased toward zero and rate
      dependency plots revealed increases in lower rates early in the interval and
      decreases in higher rates toward the end of the interval. Effects were similar in
      the presence of both stimuli. However, an analysis of post-reinforcement pauses
      and local response rates broken down by transitions revealed a differential
      effect. As the dose increased, local response rates following a wheel-running
      reinforcer were affected more than those following a sucrose reinforcer.

PMID- 15961962
TI  - Sharing of the home base: a social test in rats.
AB  - The open field provides abundant opportunities for a pair of rats to express
      social interactions. Rats demonstrate social proximity while exploring the open
      field and also during simultaneous occupancy of a home base (HB). The HB is
      defined as a place in the field for which rats show a long-term preference, both
      in terms of occupancy and as a starting and ending point of exploratory
      excursions. In the present study, the social proximity of pairs of rats treated
      with phencyclidine (PCP; 2 mg/kg) or saline (Sal), and rats treated with
      clozapine (CLZ; 1.3 mg/kg) alone or in combination with PCP (CLZ-PCP), was
      videotaped and analysed algorithmically. PCP was tested for its disruptive
      effects on social interactions, and CLZ was tested for its ability to reverse
      some forms of the disruptive effects of PCP. The results showed that PCP reduced
      the rate of pairs establishing a common HB and shortened social HB occupancy, but
      had no effect on episodes of social exploration in the field. These findings
      demonstrate that the antisocial effect of PCP cannot be generalized across the
      entire spectrum of behavioural states in the open field. CLZ further decreased
      rather than increased social HB occupancy. This effect was derived from the
      reduction in rate of pairs establishing a common HB.

PMID- 15961963
TI  - Parenteral antioxidant treatment preserves temporal discrimination following
      intrahippocampal aggregated Abeta(1-42) injections.
AB  - There is evidence that oxidative stress may play a role in the neuropathology of
      Alzheimer's disease (AD). This study used an aggregated beta-amyloid (Abeta)
      injection model of AD in the rat, and a recycling conjunctive schedule of food
      reinforcement to examine the effects of bilateral intrahippocampal injections of
      aggregated Abeta(1-42) (5.0 microl/side) on temporal discrimination, and the
      efficacy of the antioxidant alpha-tocopherol (150 mg/kg daily p.o.) in
      alleviating these effects. The results indicated that bilateral intrahippocampal
      injections of aggregated Abeta(1-42) detrimentally affected temporal
      discrimination from five-day block 31-35 post-injections until the end of the
      study (90 days post-injections). Daily treatment with alpha-tocopherol improved
      temporal discrimination under the recycling conjunctive schedule following
      aggregated Abeta(1-42) injections from the five-day block 61-65 days until the
      end of the study.

PMID- 15961964
TI  - Acute effects of lorazepam on laboratory measures of aggressive and escape
      responses of adult male parolees.
AB  - Acute benzodiazepine administrations typically decrease aggressive responding,
      but increases in aggression have been reported in some studies. The
      benzodiazepine lorazepam has been studied less frequently than other
      benzodiazepines in aggression research, although it is often used to suppress
      violent aggression in patients. The present study was designed to investigate the
      effects of acute administrations of lorazepam on aggressive responding in adult
      humans on a laboratory aggression task. Eight adult males participated in
      experimental sessions on the Point Subtraction Aggression Paradigm (PSAP), which
      provided subjects with aggressive, escape and monetary-reinforced response
      options. Acute oral doses (1, 2 and 4 mg) of lorazepam decreased both aggressive
      responding and monetary-reinforced responding in seven of eight subjects. In one
      subject, lorazepam produced dose-dependent increases in aggressive responding.
      The effects of lorazepam on escape responding were the same as the effects on
      aggressive responding. The results are consistent with prior research using the
      PSAP and clinical data showing that benzodiazepines generally decrease
      aggression, and contrast with other studies that have shown that benzodiazepines
      can increase aggression. Since lorazepam affected both aggressive and escape
      responding, it is suggested that while lorazepam often produces sedation, it also
      modifies human aggressive responding, in part, by suppressing reactions to
      aversive stimuli.

PMID- 15961965
TI  - Cross-reinstatement by cocaine and amphetamine of morphine-induced place
      preference in mice.
AB  - The cross-reinstatement by psychostimulants of a conditioned place preference
      (CPP) induced by morphine was evaluated in mice. In Experiment 1, we examined the
      effects of a single dose of cocaine and amphetamine on a previously extinguished
      morphine CPP. After acquisition of CPP induced by morphine (40 mg/kg), animals
      underwent daily extinction sessions of 15 min duration until the CPP was
      extinguished. Subsequently, animals received a non-contingent injection of
      cocaine (25 mg/kg) or amphetamine (4 mg/kg), which produced the reinstatement of
      the extinguished morphine-induced CPP. In Experiment 2, we evaluated the
      reinstating effects of several priming doses of cocaine (Experiment 2A) or
      amphetamine (Experiment 2B). As in the first experiment, after conditioning with
      morphine (40 mg/kg), mice underwent daily 15 min extinction sessions. When the
      preference was no longer evident, we tested the effects of cocaine (0, 6.25,
      12.5, 25 and 50 mg/kg) and amphetamine (0, 0.5, 1, 2 and 4 mg/kg) on the
      reinstatement of CPP. Doses from 12.5 mg/kg of cocaine upward and doses from 1
      mg/kg of amphetamine upward effectively reinstated CPP. Our results demonstrate
      cross-reinstatement with psychostimulants and opiates, suggesting that in
      abstinent individuals, drug exposure can produce craving for the previously
      abused drug and relapse.

PMID- 15961966
TI  - GABAergic modulation of the discriminative stimulus effects of methamphetamine.
AB  - To assess whether gamma-aminobutyric acid (GABA) modulation of dopamine is
      important in mediation of the discriminative stimulus effects of methamphetamine,
      the GABA compounds chlordiazepoxide (benzodiazepine site agonist), pentobarbital
      (barbiturate site agonist), bicuculline and pentylenetetrazol (GABA(A) receptor
      antagonists) were tested in Sprague-Dawley rats trained to discriminate
      methamphetamine (1 mg/kg, i.p.) from saline. Each of the compounds produced
      modest amounts of methamphetamine-appropriate responding (20-35%) when tested
      alone. When tested in combination with methamphetamine, the antagonists
      (bicuculline and pentylenetetrazol) failed to shift the methamphetamine dose
      effect curve. In contrast, chlordiazepoxide (25 mg/kg, i.p.) reduced
      methamphetamine-appropriate responding at each dose of methamphetamine tested,
      and pentobarbital (10 mg/kg, i.p.) dose-dependently decreased the discriminative
      stimulus effects of 1 mg/kg methamphetamine. In conclusion, GABA(A) antagonists
      and positive modulators likely do not produce methamphetamine-like stimulus
      effects. However, activation of GABA(A) receptors can interfere with the
      discriminative stimulus effects of methamphetamine.

PMID- 15961967
TI  - Reduced sensitivity to sucrose in rats bred for helplessness: a study using the
      matching law.
AB  - Anhedonia is a core symptom of depression. As it cannot be directly assessed in
      rodents, anhedonia is usually inferred from a reduced consumption of, or
      preference for, a reinforcer. In the present study we tried to improve the
      measurement of anhedonia by performing a detailed preference analysis based on
      the generalized matching law and tested its sensitivity in rats congenitally
      prone (cLH) or resistant (cNLH) to learned helplessness. According to the current
      interpretation of learned helplessness as a model for depression, a reduction in
      the rewarding properties of sucrose in cLH rats was hypothesized. Our results
      revealed that the 'preference allocation' index provided by this test, but not
      the traditional measures of sucrose consumption or preference over water, was
      significantly lower in cLH rats, and was correlated with the helpless behaviour
      as measured in an escape procedure. Therefore, it is clear that more subtle
      preference measures provided by the analysis of choice using the matching law
      principles are more sensitive and discriminative than those based on consumption
      of, or preference for, a single concentration of sucrose over water. Moreover,
      our data are in agreement with the proposed relationship between helplessness and
      sucrose preference, and support the usefulness of the cLH and cNLH rats as a
      model of depression.

PMID- 15961968
TI  - Micafungin (Mycamine) for fungal infections.
AB  - A new intravenous drug for prophylaxis and treatment of Candida infections.

PMID- 15961969
TI  - Viagra and loss of vision.

PMID- 15961970
TI  - Vagus nerve stimulation for depression.
AB  - An implanted device for treatment-resistant depression.

PMID- 15961971
TI  - Drugs for acne, rosacea and psoriasis.

PMID- 15961977
TI  - Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study.
AB  - BACKGROUND AND OBJECTIVE: Polymorphic cytochrome P450 (CYP) 2D6 activity has been
      shown to be a determinant of the pharmacokinetics and pharmacodynamics of
      tramadol via hepatic phase I O -demethylation of (+)-tramadol to (+)-O
      desmethyltramadol. Our objective was to investigate whether tramadol can be used
      as a probe for CYP2D6 phenotyping by determining the concordance between the 8
      hour tramadol and 12-hour sparteine metabolic urinary ratios. METHODS: Sparteine
      phenotyping test was carried out in 278 healthy, white subjects. At a minimum of
      2 weeks later, each subject took 50 mg tramadol hydrochloride followed by 8-hour
      urine collection, and a venous blood sample was drawn from 276 subjects. Urine
      and plasma concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol were
      determined. CYP2D6 genotyping was performed with regard to *3, *4, *6, and *9
      alleles. RESULTS: There were 28 poor metabolizers of sparteine (10.1% [confidence
      interval, 6.8%-14.2%]). Very low recoveries of (+)-M1 were found in poor
      metabolizers (0.53% [range, 0.1%-1.1%]) compared with extensive metabolizers
      (8.7% [range, 1.7%-23.2%]). A bimodal distribution of the metabolic ratio of (-)
      M1/(+)-M1 was found. The visual antimode was 2.0. This new phenotype test had
      only 1 misclassified subject compared with sparteine phenotyping (sensitivity and
      negative predictive value, 100%; specificity, 99.6%; positive predictive value,
      96.6%). Of the 28 sparteine poor metabolizers, 26 were found to be genotypically
      poor metabolizers with regard to the inactivating mutations *3, *4, and *6.
      CONCLUSION: Fifty milligrams of tramadol is an alternative CYP2D6 phenotype probe
      by use of the 8-hour urinary ratio of (-)-M1/(+)-M1. The poor metabolizers have a
      metabolic ratio of 2.0 or higher.

PMID- 15961978
TI  - Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of
      repaglinide pharmacokinetics.
AB  - BACKGROUND AND OBJECTIVE: A large interindividual variability exists in the
      plasma concentrations of repaglinide. Our aim was to investigate possible
      associations between the pharmacokinetics of repaglinide and single nucleotide
      polymorphisms (SNPs) in the genes encoding for the drug transporters organic
      anion transporting polypeptide 1B1 (OATP1B1) (SLCO1B1 ) and P-glycoprotein ( MDR1
      , ABCB1 ) and the drug-metabolizing enzymes cytochrome P450 (CYP) 2C8 and CYP3A5.
      METHODS: A total of 56 healthy volunteers ingested a single 0.25-mg dose of
      repaglinide. Plasma repaglinide and blood glucose concentrations were measured
      for up to 7 hours. All subjects were genotyped for the -11187G>A and 521T>C SNPs
      in SLCO1B1 and the 3435C>T and 2677G>T/A SNPs in ABCB1 , as well as for the
      CYP2C8*3 (416G>A, 1196A>G), CYP2C8*4 (792C>G), and CYP3A5*3 (6986A>G) alleles.
      RESULTS: The area under the plasma concentration-time curve from time 0 to
      infinity [AUC(0-infinity)] and peak concentration in plasma (Cmax) of repaglinide
      varied 16.9-fold and 10.7-fold, respectively, between individual subjects.
      Multiple regression analyses indicated that the SLCO1B1 521T>C SNP and the
      CYP2C8*3 allele were independent predictors of the AUC(0-infinity) and Cmax of
      repaglinide (adjusted multiple R2 = 45% and 36%, respectively). In subjects with
      the SLCO1B1 521CC genotype, the AUC(0-infinity) of repaglinide was 107% and 188%
      higher, respectively, than in subjects with the SLCO1B1 521TC or 521TT
      (reference) genotype (P < .0001). In subjects with the CYP2C8*1/*3 genotype, the
      AUC(0-infinity) and Cmax of repaglinide were 48% and 44% lower, respectively,
      than in those with the CYP2C8*1/*1 genotype (P < .05). The pharmacokinetics of
      repaglinide was not associated with the studied ABCB1 SNPs or the CYP3A5*3
      allele. The elimination half-life of repaglinide was not associated with any SNP.
      Only the SLCO1B1 -11187GA genotype was significantly associated with an enhanced
      effect of repaglinide on blood glucose. CONCLUSIONS: Genetic polymorphism in
      SLCO1B1 is a major determinant of interindividual variability in the
      pharmacokinetics of repaglinide. The effect of SLCO1B1 polymorphism on the
      pharmacokinetics of repaglinide may be clinically important.

PMID- 15961979
TI  - Allelic variants of cytochrome P450 2C9 modify the interaction between
      nonsteroidal anti-inflammatory drugs and coumarin anticoagulants.
AB  - INTRODUCTION: Cytochrome P450 (CYP) plays a key role in the metabolism of
      coumarin anticoagulants and nonsteroidal anti-inflammatory drugs (NSAIDs).
      Because CYP2C9 is a genetically polymorphic enzyme, genetic variability could
      play an important role in the potential interaction between NSAIDs and coumarins.
      We investigated whether NSAIDs were associated with overanticoagulation during
      therapy with coumarins and evaluated the effect of the CYP2C9 polymorphisms on
      this potential interaction. METHODS: We conducted a population-based cohort study
      among patients of an anticoagulation clinic who were treated with acenocoumarol
      or phenprocoumon between April 1, 1991, and May 31, 2003, and whose CYP2C9 status
      was known. Patients were followed up until an international normalized ratio
      (INR) of 6.0 or greater was reached or until the end of treatment, death, or the
      end of the study. Proportional hazards regression analysis was used to estimate
      the risk of an INR of 6.0 or greater in relation to concomitant use of a coumarin
      anticoagulant and NSAIDs after adjustment for several potentially confounding
      factors. To study effect modification by CYP2C9 genotype, stratified analyses
      were performed for wild-type patients and patients with a variant genotype.
      RESULTS: Of the 973 patients in the cohort, 415 had an INR of 6.0 or greater.
      Several NSAIDs increased the risk of overanticoagulation. The risk of
      overanticoagulation was 2.98 (95% confidence interval, 1.09-7.02) in coumarin
      treated patients taking NSAIDs with a CYP2C9*2 allele and 10.8 (95% confidence
      interval, 2.57-34.6) in those with a CYP2C9*3 allele. CONCLUSIONS: Several NSAIDs
      were associated with overanticoagulation. For NSAIDs that are known CYP2C9
      substrates, this risk was modified by allelic variants of CYP2C9. More frequent
      INR monitoring of patients taking NSAIDs is warranted.

PMID- 15961980
TI  - Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and
      drug interactions of intravenous lorazepam in healthy volunteers.
AB  - OBJECTIVE: Our objective was to investigate the effect of the uridine 5'
      diphosphate-glucuronosyltransferase (UGT) 2B15 genetic polymorphism on the
      pharmacokinetics and pharmacodynamics of lorazepam in basal, inhibited, and
      induced metabolic states in healthy normal volunteers. METHODS: Twenty-four
      healthy subjects were enrolled and grouped into UGT2B15*1/*1 or UGT2B15*2/*2
      genotype groups. The pharmacokinetic and pharmacodynamic profiles of intravenous
      lorazepam were characterized before and after inhibition with 600 mg valproate
      once daily for 4 days and after induction with rifampin (INN, rifampicin)
      pretreatment (600 mg once daily for 10 days), with a washout period of 10 days
      between. The plasma concentrations of lorazepam and lorazepam glucuronide were
      analyzed before and at 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 hours after
      lorazepam administration by liquid chromatography-tandem mass spectrometry.
      Visual analog scale assessments and psychomotor coordination tests were
      administered before and up to 12 hours after drug administration. RESULTS: The
      UGT2B15*2/*2 group showed 0.58-fold (95% confidence interval, 0.43-0.72; P <
      .0001) lower systemic clearance during the basal state and 1.37-fold (95%
      confidence interval, 1.05-1.88; P = .037) higher area under the visual analog
      scale-time curve during the induced state compared with the UGT2B15*1/*1 group.
      The mean systemic clearance of lorazepam decreased by 20% in the inhibited state
      and increased by 140% in the induced state. During the inhibited or induced
      state, absolute values of clearance were consistently lower in the *2/*2 group,
      but the percent changes from baseline did not differ significantly by genotype.
      CONCLUSIONS: Our results suggest that the UGT2B15*2 polymorphism is a major
      determinant of interindividual variability with respect to the pharmacokinetics
      and pharmacodynamics of lorazepam.

PMID- 15961981
TI  - Insulin-mediated venodilation is impaired in young, healthy carriers of the 825T
      allele of the G-protein beta3 subunit gene (GNB3).
AB  - OBJECTIVE: A C825T polymorphism has been identified for the gene encoding the G
      protein beta 3 subunit ( GNB3 ). The 825T allele is associated with hypertension
      and obesity, which in turn are closely linked with resistance to the metabolic
      and vascular effects of insulin. We hypothesized that venodilation in response to
      insulin would be impaired in GNB3 825T-allele carriers. Because vasodilatory
      properties of insulin are mainly mediated by nitric oxide, we also investigated
      the influence of the T-786C polymorphism of the gene for endothelial nitric oxide
      synthase ( NOS3 ) on insulin-mediated venous responses. METHODS: We used the
      linear variable transducer technique to compare dorsal hand vein compliance in 31
      young, healthy men ( GNB3 C825T: 15 CC, 14 CT, and 2 TT; NOS3 T-786C: 14 TT, 13
      TC, and 4 CC). Individual dose-response curves to phenylephrine (3.2-10,000
      ng/min) were established, and veins were preconstricted by a constant infusion of
      phenylephrine at the individual dose needed to procure 70% of maximal
      constriction. Then insulin was infused (50-250,000 microU/min), and the changes
      in venous diameter were recorded. RESULTS: Venous response to insulin was
      biphasic, with venoconstriction at low doses being followed by venodilation at
      higher doses. Insulin dose-response curves of GNB3 825T-allele carriers were
      significantly shifted to the right (ANOVA, P < .001, versus CC). NOS3 T-786C
      allele carrier status had no influence on insulin-induced vascular responses ( P
      = .60 for TC/CC versus TT). CONCLUSION: This study is the first to show the
      influence of a genetic polymorphism on insulin-mediated venodilation in men in
      vivo. Further studies are needed to determine whether these results translate to
      other vascular beds, and possible gender-specific differences remain to be
      investigated.

PMID- 15961982
TI  - Imaging P-glycoprotein transport activity at the human blood-brain barrier with
      positron emission tomography.
AB  - BACKGROUND: Numerous knockout mouse studies have revealed that P-glycoprotein (P
      gp) significantly limits drug distribution across the mouse blood-brain barrier
      (BBB). To determine the importance of P-gp at the human BBB, we developed a state
      of-the-art, noninvasive, quantitative imaging technique to measure P-gp activity
      by use of carbon 11-labeled verapamil as the P-gp substrate and cyclosporine
      (INN, ciclosporin) as the P-gp inhibitor. METHODS: In brief, 11C-verapamil
      (approximately 0.2 mCi/kg) was administered to healthy volunteers (n = 12 [6
      women and 6 men]) as an intravenous infusion over a period of approximately 1
      minute before and after at least a 1-hour infusion of cyclosporine (2.5 mg x kg(
      1) x h(-1)). Arterial blood samples and brain positron emission tomography images
      were obtained at frequent intervals for 45 minutes. Both blood and plasma
      radioactivity contents were determined in each verapamil sample. The content of
      verapamil and its metabolites in the 20- and 45-minute plasma samples was
      determined by a rapid solid-phase extraction method. The brain uptake of 11C
      radioactivity (brain area under the curve [AUCbrain ]/blood area under the curve
      [AUCblood]) was determined in the presence and absence of cyclosporine. RESULTS:
      The AUCbrain/AUCblood ratio of 11C-radioactivity was increased by 88% +/- 20%
      (1.02 +/- 0.18 versus 0.55 +/- 0.10, P < .001) in the presence of cyclosporine
      (mean blood concentration, 2.8 +/- 0.4 micromol/L) without affecting 11C
      verapamil metabolism or plasma protein binding. The corresponding increases for
      the brain white and gray matter were 84% +/- 13% and 84% +/- 18%, respectively.
      CONCLUSIONS: This is the first time that P-gp activity at the human BBB has been
      measured. The modest inhibition of human BBB P-gp by cyclosporine has
      implications for P-gp-based drug interactions at the human BBB. Our method for
      imaging P-gp activity can be used to identify multidrug-resistant tumors or to
      determine the contribution of P-gp polymorphism, inhibition, or induction to
      interindividual variability in drug response.

PMID- 15961983
TI  - Population pharmacokinetics and exposure-response relationship of enfuvirtide in
      treatment-experienced human immunodeficiency virus type 1-infected patients.
AB  - OBJECTIVE: Our objective was to characterize population pharmacokinetics of
      enfuvirtide, 90 mg twice daily injected subcutaneously, in treatment-experienced
      human immunodeficiency virus type 1 (HIV-1)-infected patients, as well as the
      relationship between exposure and antiviral effect. METHODS: Plasma
      concentrations of enfuvirtide and HIV-1 ribonucleic acid were obtained from 628
      patients in 2 phase III studies. NONMEM software was used for population
      pharmacokinetic analysis and to assess the effects of age, gender, body weight,
      anti-gp41 antibodies, and concomitant drugs. Enfuvirtide exposure (area under the
      plasma concentration-12-hour time curve or steady-state trough concentration) was
      calculated from individual parameter estimates derived from the model. The
      decline in HIV-1 ribonucleic acid from baseline at week 2 or 24 was regressed
      against estimates of enfuvirtide exposure by a maximum effect model. The exposure
      response relationship was examined in functional monotherapy (phenotypic
      sensitivity score of 0) and combination therapy (phenotypic sensitivity score >
      or = 1). RESULTS: Enfuvirtide population pharmacokinetics was well described by a
      1-compartment model with first-order absorption and elimination. Body weight and
      female gender were identified as affecting apparent clearance but not efficacy
      and safety. Concomitant medications had no significant effect on enfuvirtide
      pharmacokinetics. Antiviral response to enfuvirtide was independent of drug
      exposure, suggesting that the approved 90-mg twice-daily dose was in the plateau
      portion of the dose-response curve. For functional monotherapy (phenotypic
      sensitivity score of 0), approximately 66% of estimated maximal effect was
      achieved at week 2 and 73% at week 24, and for combination therapy, more than 92%
      was achieved at both weeks 2 and 24. CONCLUSIONS: Body weight and gender affected
      enfuvirtide clearance, but changes in exposure did not affect efficacy or safety.
      Efficacy reached a plateau at the 90-mg twice-daily dosage in the exposure
      response curve.

PMID- 15961984
TI  - Pharmacokinetics of levetiracetam in patients with moderate to severe liver
      cirrhosis (Child-Pugh classes A, B, and C): characterization by dynamic liver
      function tests.
AB  - BACKGROUND: Levetiracetam is an antiepileptic drug approved for use as adjunctive
      therapy in adults with partial-onset seizures. We sought to investigate possible
      changes in the pharmacokinetics of levetiracetam and its metabolite ucb L057 in
      patients with liver cirrhosis, who may require dose adjustments. METHODS: A
      single dose of levetiracetam was administered to 5 healthy subjects and to
      patients with Child-Pugh class A (n = 5), B (n = 6), or C (n = 5) alcohol-induced
      cirrhosis. The pharmacokinetics of levetiracetam and ucb L057 was measured and
      correlated with biochemical liver function parameters, with creatinine clearance,
      and with kinetics of caffeine, lidocaine, and d -sorbitol as probes for specific
      liver functions. RESULTS: Dynamic liver function tests revealed a deterioration
      of liver function. The pharmacokinetics of levetiracetam and its metabolite did
      not differ between healthy subjects and those with class A or B cirrhosis.
      However, in patients with class C cirrhosis, levetiracetam total clearance was
      reduced by 57% (90% confidence interval [CI], 43%-67%; P < .001). The geometric
      mean ratio of the area under the plasma concentration-time curve for
      levetiracetam, Child-Pugh class C versus control, was 2.41 (90% CI, 1.80-3.23),
      and the geometric mean of the half-life ratio was 2.27 (90% CI, 1.74-2.97). This
      was explained by the deterioration of renal function in patients with severe
      hepatic disease. CONCLUSIONS: In pharmacokinetic studies of hepatic impairment,
      including all classes of cirrhosis may be more revealing than including only
      selected classes of liver failure. No dose adjustment of levetiracetam is
      necessary in patients with mild to moderate liver impairment; however, patients
      with severe cirrhosis should initially receive only half of the commonly
      recommended dose.

PMID- 15961985
TI  - Dosing strategy in patients with renal failure receiving enoxaparin for the
      treatment of non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: Enoxaparin therapy is recommended for the initial treatment of
      patients with non-ST-segment elevation acute coronary syndrome. However, little
      dosing information is available regarding the use of enoxaparin in patients with
      renal impairment. METHODS: We conducted a population pharmacokinetic analysis
      using anti-Xa activities measured in 532 patients (normal renal function in 34%,
      mild renal impairment in 36%, moderate renal impairment in 20%, and severe renal
      impairment in 10%) receiving subcutaneous enoxaparin (mean weight-corrected dose
      [+/-SD], 0.83 +/- 0.19 mg x kg(-1) x 12 h(-1) for an acute coronary syndrome.
      Simulations were then performed to develop a dosing strategy for patients with
      renal impairment. RESULTS: A 1-compartment model with first-order kinetics best
      fit the data. The covariate analysis showed that enoxaparin clearance was related
      to renal function and volume of distribution to total body weight. Enoxaparin
      clearance was decreased by 31% in patients with moderate renal impairment and by
      44% in patients with severe renal impairment, resulting in a significant
      accumulation with the use of the standard 1 mg . kg(-1) x 12 h(-1) dosing
      regimen. Simulations showed that a first unadjusted dose of 1 mg/kg followed by a
      regimen of 0.8 mg . kg(-1) x 12 h(-1) in patients with moderate renal impairment
      or 0.66 mg . kg(-1) x 12 h(-)1 in patients with severe renal impairment should
      avoid accumulation of enoxaparin and keep peak anti-Xa activities between 0.5 and
      1.2 IU/mL for a large majority of patients. CONCLUSIONS: An enoxaparin dosage
      reduction should be considered in acute coronary syndrome patients with
      creatinine clearance lower than 50 mL/min. A simple dosing protocol for
      enoxaparin to avoid significant accumulation in patients with moderate or severe
      renal impairment is proposed.

PMID- 15961986
TI  - Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured
      by bupropion hydroxylation.
AB  - OBJECTIVE: Our objective was to study the effect of the antiplatelet agents
      clopidogrel and ticlopidine on bupropion (INN, amfebutamone) hydroxylation, a
      probe reaction for cytochrome P450 (CYP) 2B6 activity. METHODS: Twelve healthy
      male volunteers took a single 150-mg oral dose of bupropion either alone or after
      pretreatment with 75 mg clopidogrel once daily or 250 mg ticlopidine twice daily
      for 4 days. On day 4, a single 150-mg oral dose of bupropion was administered.
      Plasma concentrations of bupropion and its CYP2B6-catalyzed metabolite,
      hydroxybupropion, were measured for up to 72 hours. RESULTS: The mean area under
      the plasma concentration-time curve (AUC) of hydroxybupropion calculated from
      time 0 to infinity was reduced by 52% ( P = .001; 95% confidence interval [CI],
      39% to 66%) by clopidogrel and by 84% ( P < .0001; 95% CI, 73% to 94%) by
      ticlopidine. Clopidogrel reduced the AUC ratio of hydroxybupropion over bupropion
      by 68% ( P = .002; 95% CI, 58% to 77%) and ticlopidine by 90% ( P = .001; 95% CI,
      85% to 96%). The AUC of bupropion was increased by 60% ( P = .02; 95% CI, 21% to
      98%) and by 85% ( P < .0001; 95% CI, 48% to 85%) with clopidogrel and
      ticlopidine, respectively. CONCLUSIONS: Both clopidogrel and ticlopidine
      significantly inhibited the CYP2B6-catalyzed bupropion hydroxylation. Patients
      receiving either clopidogrel or ticlopidine are likely to require dose
      adjustments when treated with drugs primarily metabolized by CYP2B6.

PMID- 15961987
TI  - Short-term metabolic and hemodynamic effects of ephedra and guarana combinations.
AB  - OBJECTIVE: Serious adverse health events have been reported with the use of
      dietary supplements containing ephedra and guarana. We sought to determine
      whether repeated dosing and multi-ingredient formulations contribute to the
      adverse effects of these supplements. METHODS: In this study, 16 healthy adults
      (8 women) took 2 doses each of ephedra-guarana alone, Xenadrine RFA, a
      multicomponent dietary supplement containing 25 mg ephedra alkaloids and 200 mg
      caffeine, or placebo 5 hours apart in a randomized, double-blind, 3-arm crossover
      study. RESULTS: Peak plasma ephedrine levels averaged 130 to 140 ng/mL. Compared
      with placebo, Xenadrine and ephedra-guarana significantly increased heart rate
      (maximum increase, 9.4 +/- 8.6 beats/min; P = .002), blood pressure (maximum
      increase in systolic and diastolic pressure, 11.5 +/- 10.7 mm Hg and 7.3 +/- 7.4
      mm Hg, respectively; P = .015), postprandial glucose concentration (maximum
      change, 41.0 +/- 18.8 mg/dL; P < .0001), and insulin concentration (maximum
      change, 41.2 +/- 47.8 microIU/mL; P = .005). Serum potassium concentrations were
      significantly decreased by both treatments. Hemodynamic and metabolic changes
      were observed after both the first and second doses. However, plasma free fatty
      acid concentrations increased after the first dose only. Xenadrine RFA produced
      higher increases in glucose concentration than ephedra-guarana, but no other
      pharmacodynamic differences between the treatments were found. CONCLUSIONS:
      Consumption of 2 doses of ephedra and guarana supplements, per supplement label
      recommendations, results in persistent increases in heart rate and blood pressure
      and unfavorable actions on glucose and potassium homeostasis. Such effects could
      be detrimental in persons with hypertension, atherosclerosis, or glucose
      intolerance, conditions that are strongly associated with obesity.

PMID- 15961988
TI  - A pharmacokinetic-pharmacodynamic model for the quantitative prediction of
      dofetilide clinical QT prolongation from human ether-a-go-go-related gene current
      inhibition data.
AB  - BACKGROUND: QT prolongation is an important biomarker of the arrhythmia torsades
      de pointes and appears to be related mainly to blockade of delayed inward cardiac
      rectifier potassium currents. The aim of this study was to quantify the
      relationship between in vitro human ether-a-go-go-related gene (hERG) potassium
      channel blockade and the magnitude of QT prolongation in humans for the class III
      antiarrhythmic dofetilide. METHODS: The in vitro affinity and activity of
      dofetilide were determined in recombinant cell cultures expressing the hERG
      channel, and the QT-prolonging effect of dofetilide was assessed in 5 clinical
      studies (80 healthy volunteers and 17 patients with ischemic heart disease). A
      population pharmacokinetic-pharmacodynamic analysis of the in vitro and in vivo
      data was performed in NONMEM by use of the operational model of pharmacologic
      agonism to estimate the efficiency of transduction from ion channel binding to
      Fridericia-corrected QT response. RESULTS: A 3-compartment pharmacokinetic model
      with first-order absorption characterized the time course of dofetilide
      concentrations. On the basis of an in vitro potency of 5.13 ng/mL for potassium
      current inhibition and predicted unbound dofetilide concentrations, the estimated
      transducer ratio (tau) of 6.2 suggests that the QT response plateaus before
      currents are fully blocked. In our study population, 10% hERG blockade
      corresponds to a QT prolongation of 20 ms (95% confidence interval, 12-32 ms).
      With long-term dofetilide administration, tolerance develops with a half-life of
      4.7 days. CONCLUSIONS: The current mechanism-based pharmacokinetic
      pharmacodynamic model quantified the relationship between in vitro hERG channel
      blockade and clinical QT prolongation for dofetilide. This model may prove
      valuable for assessing the risk of QT prolongation in humans for other drugs that
      selectively block the hERG channel on the basis of in vitro assays and
      pharmacokinetic properties.

PMID- 15961989
TI  - The use of tegaserod in critically ill patients with impaired gastric motility.
AB  - Studies have shown that early enteral nutrition in critically ill patients
      reduces the incidence of morbidity and death. Nonetheless, intolerance to gastric
      enteral nutrition is common in these patients as a result of gastroparesis. The
      use of prokinetic agents such as metoclopramide, domperidone, cisapride, and
      erythromycin can improve gastric emptying, but these agents are not without
      deleterious adverse effects. Tegaserod, a selective serotonin type 4 receptor
      partial agonist, was recently approved for treatment of women with irritable
      bowel syndrome. On the basis of tegaserod's mechanism of action, it was
      hypothesized that tegaserod may accelerate the return of gastric function in
      intensive care unit patients with gastroparesis. It would thus provide an
      additional agent for the management of gastroparesis with a more favorable safety
      profile. We present 3 case reports of the successful use of tegaserod in
      intensive care unit patients with impaired gastric motility. To our knowledge,
      the use of tegaserod in this setting has not been reported or studied previously.

PMID- 15961990
TI  - Detection of CYP2C9*5 in a white Brazilian subject.

PMID- 15961996
TI  - Negative feedback regulation among SR splicing factors encoded by Rbp1 and Rbp1
      like in Drosophila.
AB  - SR proteins constitute a widely conserved family of splicing regulators. Negative
      autoregulation of SR proteins has been proposed to exert homeostatic control on
      the splicing environment, but few examples have been studied and the role of
      isoforms that lack the RS domain is unclear. We show that genes Rbp1 and Rbp1
      like, which encode Drosophila homologs of mammalian SRp20, negatively
      autoregulate and crossregulate at the level of alternative 3' splice site
      selection. This adjusts the relative expression of isoforms with either an RS
      domain or unrelated C-terminal domains (ALT) that are rich in serine and
      threonine. The effects of RBP1-ALT on splicing of doublesex and Rbp1-like are
      opposite to those of RBP1-RS and RBP1L-RS. RBP1-ALT and -RS exert opposing
      negative feedback on the ALT/RS ratio. However, RBP1-ALT inhibits the expression
      of RBP1-RS while stimulating that of RBP1L-RS. This asymmetry may contribute to
      changes in the RBP1-RS/RBP1L-RS ratio that are observed during development. These
      results provide the first example of a feedback-regulated SR protein network with
      evidence of an active homeostatic role for alternative isoforms.

PMID- 15961997
TI  - Nuclear speckles and nucleoli targeting by PIP2-PDZ domain interactions.
AB  - PDZ (Postsynaptic density protein, Disc large, Zona occludens) domains are
      protein-protein interaction modules that predominate in submembranous scaffolding
      proteins. Recently, we showed that the PDZ domains of syntenin-1 also interact
      with phosphatidylinositol 4,5-bisphosphate (PIP2) and that this interaction
      controls the recruitment of the protein to the plasma membrane. Here we evaluate
      the general importance of PIP2-PDZ domain interactions. We report that most PDZ
      proteins bind weakly to PIP2, but that syntenin-2, the closest homolog of
      syntenin-1, binds with high affinity to PIP2 via its PDZ domains. Surprisingly,
      these domains target syntenin-2 to nuclear PIP2 pools, in nuclear speckles and
      nucleoli. Targeting to these sites is abolished by treatments known to affect
      these PIP2 pools. Mutational and domain-swapping experiments indicate that high
      affinity binding to PIP2 requires both PDZ domains of syntenin-2, but that its
      first PDZ domain contains the nuclear PIP2 targeting determinants. Depletion of
      syntenin-2 disrupts the nuclear speckles-PIP2 pattern and affects cell survival
      and cell division. These findings show that PIP2-PDZ domain interactions can
      directly contribute to subnuclear assembly processes.

PMID- 15961998
TI  - Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum-infected
      erythrocytes.
AB  - The human malarial parasite Plasmodium falciparum exports proteins to
      destinations within its host erythrocyte, including cytosol, surface and
      membranous profiles of parasite origin termed Maurer's clefts. Although several
      of these exported proteins are determinants of pathology and virulence, the
      mechanisms and trafficking signals underpinning protein export are largely
      uncharacterized-particularly for exported transmembrane proteins. Here, we have
      investigated the signals mediating trafficking of STEVOR, a family of
      transmembrane proteins located at the Maurer's clefts and believed to play a role
      in antigenic variation. Our data show that, apart from a signal sequence, a
      minimum of two addition signals are required. This includes a host cell targeting
      signal for export to the host erythrocyte and a transmembrane domain for final
      sorting to Maurer's clefts. Biochemical studies indicate that STEVOR traverses
      the secretory pathway as an integral membrane protein. Our data suggest general
      principles for transport of transmembrane proteins to the Maurer's clefts and
      provide new insights into protein sorting and trafficking processes in P.
      falciparum.

PMID- 15961999
TI  - Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by
      constitutive CREB activation.
AB  - Salivary gland tumors, a group of histologically diverse benign and malignant
      neoplasms, represent a challenging problem for diagnosis and treatment. A
      specific recurring t(11;19)(q21;p13) translocation is associated with two types
      of salivary gland tumors, mucoepidermoid carcinomas and Warthin's tumors. This
      translocation generates a fusion protein comprised of the N-terminal CREB (cAMP
      response element-binding protein)-binding domain of the CREB regulator MECT1
      (Mucoepidermoid carcinoma translocated-1) and the C-terminal transcriptional
      activation domain of the Notch coactivator Mastermind-like 2 (MAML2). Here, we
      demonstrate that the MECT1-MAML2 fusion protein induces expression of multiple
      genes known to be CREB transcriptional targets. MECT1-MAML2 was found to bind to
      CREB, recruit p300/CBP into the CREB complex through a binding domain on MAML2,
      and constitutively activate CREB-dependent transcription. The transforming
      activity of MECT1-MAML2 was markedly reduced by blocking CREB DNA binding. Thus,
      this fusion oncogene mimics constitutive activation of cAMP signaling, by
      activating CREB directly. This study has identified a novel, critical mechanism
      of transformation for an oncogene associated very specifically with salivary
      gland tumors, and identified potential targets for the development of novel
      therapies.

PMID- 15962000
TI  - Pseudouridylation of yeast U2 snRNA is catalyzed by either an RNA-guided or RNA
      independent mechanism.
AB  - Yeast U2 small nuclear RNA (snRNA) contains three pseudouridines (Psi35, Psi42,
      and Psi44). Pus7p and Pus1p catalyze the formation of Psi35 and Psi44,
      respectively, but the mechanism of Psi42 formation remains unclear. Using a U2
      substrate containing a single (32)P radiolabel at position 42, we screened a GST
      ORF library for pseudouridylase activity. Surprisingly, we found a Psi42-specific
      pseudouridylase activity that coincided with Nhp2p, a protein component of a Box
      H/ACA sno/scaRNP (small nucleolar/Cajal body-specific ribonucleoprotein). When
      isolated by tandem affinity purification (TAP), the other protein components of
      the H/ACA sno/scaRNP also copurified with the pseudouridylase activity.
      Micrococcal nuclease-treated TAP preparations were devoid of pseudouridylase
      activity; however, activity was restored upon addition of RNAs from TAP
      preparations. Pseudouridylation reconstitution using RNAs from a Box H/ACA RNA
      library identified snR81, a snoRNA known to guide rRNA pseudouridylation, as the
      Psi42-specific guide RNA. Using the snR81-deletion strain, Nhp2p- or Cbf5p
      conditional depletion strain, and a cbf5 mutation strain, we further demonstrated
      that the pseudouridylase activity is dependent on snR81 snoRNP in vivo. Our data
      indicate that snRNA pseudouridylation can be catalyzed by both RNA-dependent and
      RNA-independent mechanisms.

PMID- 15962001
TI  - Immunodetection of disease-associated mutant PrP, which accelerates disease in
      GSS transgenic mice.
AB  - The absence of infectivity-associated, protease-resistant prion protein (PrP(Sc))
      in the brains of spontaneously sick transgenic (Tg) mice overexpressing PrP
      linked to Gerstmann-Straussler Scheinker syndrome, and the failure of gene
      targeted mice expressing such PrP to develop disease spontaneously, challenged
      the concept that mutant PrP expression led to spontaneous prion production. Here,
      we demonstrate that disease in overexpressor Tg mice is associated with
      accumulation of protease-sensitive aggregates of mutant PrP that can be
      immunoprecipitated by the PrP(Sc)-specific monoclonal antibody designated 15B3.
      Whereas Tg mice expressing multiple transgenes exhibited accelerated disease when
      inoculated with disease-associated mutant PrP, Tg mice expressing mutant PrP at
      low levels failed to develop disease either spontaneously or following
      inoculation. These studies indicate that inoculated mutant PrP from diseased mice
      promotes the aggregation and accumulation of pre-existing pathological forms of
      mutant PrP produced as a result of transgene overexpression. Thus, while
      pathological mutant PrP possesses a subset of PrP(Sc) characteristics, we now
      show that the attribute of prion transmission suggested by previous studies is
      more accurately characterized as disease acceleration.

PMID- 15962002
TI  - A Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and
      inhibitory mechanisms.
AB  - We have identified two LIM domain proteins, LimF and ChLim, from Dictyostelium
      that interact with each other and with the small, Rab5-related, Rab21 GTPase to
      collectively regulate phagocytosis. To investigate in vivo functions, we
      generated cell lines that lack or overexpress LimF and ChLim and strains that
      express activating or inhibiting variants of Rab21. Overexpression of LimF, loss
      of ChLim, or expression of constitutively active Rab21 increases the rate of
      phagocytosis above that of wild type. Conversely, loss of LimF, overexpression of
      ChLim, or expression of a dominant-negative Rab21 inhibits phagocytosis. Our
      studies using cells carrying multiple mutations in these genes further indicate
      that ChLim antagonizes the activating function of Rab21-GTP during phagocytosis;
      in turn, LimF is required for Rab21-GTP function. Finally, we demonstrate that
      ChLim and LimF localize to the phagocytic cup and phago-lysosomal vesicles. We
      suggest that LimF, ChLim, and activated Rab21-GTP participate as a novel
      signaling complex that regulates phagocytic activity.

PMID- 15962003
TI  - Kir6.2 mutations causing neonatal diabetes provide new insights into Kir6.2-SUR1
      interactions.
AB  - ATP-sensitive K(+) (K(ATP)) channels, comprised of pore-forming Kir6.2 and
      regulatory SUR1 subunits, play a critical role in regulating insulin secretion.
      Binding of ATP to Kir6.2 inhibits, whereas interaction of MgATP with SUR1
      activates, K(ATP) channels. We tested the functional effects of two Kir6.2
      mutations (Y330C, F333I) that cause permanent neonatal diabetes mellitus, by
      heterologous expression in Xenopus oocytes. Both mutations reduced ATP inhibition
      and increased whole-cell currents, which in pancreatic beta-cells is expected to
      reduce insulin secretion and precipitate diabetes. The Y330C mutation reduced ATP
      inhibition both directly, by impairing ATP binding (and/or transduction), and
      indirectly, by stabilizing the intrinsic open state of the channel. The F333I
      mutation altered ATP binding/transduction directly. Both mutations also altered
      Kir6.2/SUR1 interactions, enhancing the stimulatory effect of MgATP (which is
      mediated via SUR1). This effect was particularly dramatic for the Kir6.2-F333I
      mutation, and was abolished by SUR1 mutations that prevent MgATP
      binding/hydrolysis. Further analysis of F333I heterozygous channels indicated
      that at least three SUR1 must bind/hydrolyse MgATP to open the mutant K(ATP)
      channel.

PMID- 15962004
TI  - VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor
      angiogenesis.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is
      essential in vasculogenesis and angiogenesis. We have generated a pan
      phosphorylation site map of VEGFR-2 and identified one major tyrosine
      phosphorylation site in the kinase insert (Y951), in addition to two major sites
      in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation
      of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells,
      whereas phosphorylation of Y951 was identified in a subset of vessels.
      Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed
      in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951
      peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress
      fibers and migration, but not mitogenesis. Tumor vascularization and growth was
      reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling
      in pathological angiogenesis.

PMID- 15962006
TI  - Enforced expression of KDR receptor promotes proliferation, survival and
      megakaryocytic differentiation of TF1 progenitor cell line.
AB  - Vascular endothelial growth factor (VEGF) receptor-2/kinase insert domain
      containing receptor (KDR) is expressed in primitive hematopoietic cells, in
      megakaryocytes and platelets. In primitive hematopoiesis KDR mediates cell
      survival via autocrine VEGF, while its effect on cell growth and differentiation
      has not been elucidated. We induced enforced KDR expression in the granulocyte
      macrophage-colony-stimulating factor (GM-CSF)-dependent TF1 progenitor cell line
      (TF1-KDR), treated the cells with VEGF and analyzed their response. In GM-CSF
      deprived cells, VEGF induces cell proliferation and protection against apoptosis,
      followed by enhanced expression of megakaryocytic (MK) markers. Combined with GM
      CSF, VEGF induces a mild proliferative stimulus, followed by cell adherence,
      accumulation in G0/G1, massive MK differentiation and Fas-mediated apoptosis.
      Accordingly, we observed that MK-differentiating cells, derived from
      hematopoietic progenitors, produce VEGF, express KDR, inhibition of which reduces
      MK differentiation, indicating a key role of KDR in megakaryopoiesis. In
      conclusion, TF1-KDR cells provide a reliable model to investigate the biochemical
      and molecular mechanisms underlying hematopoietic progenitor proliferation,
      survival and MK differentiation.

PMID- 15962007
TI  - Neutrophils: dead or effete? Cell surface phenotype and implications for
      phagocytic clearance.

PMID- 15962005
TI  - Intravenous apoptotic spleen cell infusion induces a TGF-beta-dependent
      regulatory T-cell expansion.
AB  - Apoptotic leukocytes are endowed with immunomodulatory properties that can be
      used to enhance hematopoietic engraftment and prevent graft-versus-host disease
      (GvHD). This apoptotic cell-induced tolerogenic effect is mediated by host
      macrophages and not recipient dendritic cells or donor phagocytes present in the
      bone marrow graft as evidenced by selective cell depletion and trafficking
      experiments. Furthermore, apoptotic cell infusion is associated with TGF-beta
      dependent donor CD4+CD25+ T-cell expansion. Such cells have a regulatory
      phenotype (CD62L(high) and intracellular CTLA-4+), express high levels of
      forkhead-box transcription factor p3 (Foxp3) mRNA and exert ex vivo suppressive
      activity through a cell-to-cell contact mechanism. In vivo CD25 depletion after
      apoptotic cell infusion prevents the apoptotic cell-induced beneficial effects on
      engraftment and GvHD occurrence. This highlights the role of regulatory T cells
      in the tolerogenic effect of apoptotic cell infusion. This novel association
      between apoptosis and regulatory T-cell expansion may also contribute to
      preventing deleterious autoimmune responses during normal turnover.

PMID- 15962008
TI  - Functional intrinsic and extrinsic apoptotic pathways in human fetal mesenchymal
      stem cells.

PMID- 15962009
TI  - Locating ligand binding and activation of a single antiporter.
AB  - Single-molecule force spectroscopy was applied to unfold individual Na(+)/H(+)
      antiporters NhaA from membrane patches. The force-extension curves contained
      detailed information about the strength and location of molecular interactions
      established within NhaA. Although molecular interactions that stabilize secondary
      structure elements remained unaffected on switching NhaA into its functional
      state, those that are assigned to the Na(+)-binding site changed markedly. These
      interactions were formed only in the presence of Na(+), with their full strength
      being established at pH approximately 6. This finding is in apparent contrast to
      measurements that suggest that NhaA is fully active at pH 7. Statistical
      analysis, however, showed that not all NhaA molecules activated this molecular
      interaction at pH 6, but at pH 7. This implies that the molecular interactions
      established on Na(+) binding may represent an early step in NhaA activation. The
      direct observation of molecular interactions established within an antiporter
      provides new insights into their activation mechanisms.

PMID- 15962010
TI  - Sulphatase activities are regulated by the interaction of sulphatase-modifying
      factor 1 with SUMF2.
AB  - Sulphatases undergo a unique post-translational modification that converts a
      highly conserved cysteine located within their active site into formylglycine.
      This modification is necessary for the catalytic activities of the sulphatases,
      and it is generated by the protein product of sulphatase-modifying factor 1
      (SUMF1), the gene mutated in multiple sulphatase deficiency (MSD). A paralogous
      gene, SUMF2, was discovered through its sequence similarity to SUMF1. We present
      evidence that SUMF2 colocalizes with SUMF1 within the endoplasmic reticulum and
      that the two proteins form heterodimers. SUMF1 and SUMF2 also form homodimers. In
      addition, SUMF2 is able to associate with the sulphatases with and without SUMF1.
      We have previously shown that co-transfection of SUMF1 with the sulphatase
      complementary DNAs greatly enhances the activities of the overexpressed
      sulphatases. Here, we show that SUMF2 inhibits the enhancing effects of SUMF1 on
      sulphatases, suggesting that the SUMF1-SUMF2 interaction represents a further
      level of control of these sulphatase activities.

PMID- 15962011
TI  - Sprouty2 acts at the Cbl/CIN85 interface to inhibit epidermal growth factor
      receptor downregulation.
AB  - The ubiquitin ligase Cbl mediates ubiquitination of activated receptor tyrosine
      kinases (RTKs) and interacts with endocytic scaffold complexes, including
      CIN85/endophilins, to facilitate RTK endocytosis and degradation. Several
      mechanisms regulate the functions of Cbl to ensure the fine-tuning of RTK
      signalling and cellular homeostasis. One regulatory mechanism involves the
      binding of Cbl to Sprouty2, which sequesters Cbl away from activated epidermal
      growth factor receptors (EGFRs). Here, we show that Sprouty2 associates with
      CIN85 and acts at the interface between Cbl and CIN85 to inhibit EGFR
      downregulation. The CIN85 SH3 domains A and C bind specifically to proline
      arginine motifs present in Sprouty2. Intact association between Sprouty2, Cbl and
      CIN85 is required for inhibition of EGFR endocytosis as well as EGF-induced
      differentiation of PC12 cells. Moreover, Sprouty4, which lacks CIN85-binding
      sites, does not inhibit EGFR downregulation, providing a molecular explanation
      for functional differences between Sprouty isoforms. Sprouty2 therefore acts as
      an inducible inhibitor of EGFR downregulation by targeting both the Cbl and CIN85
      pathways.

PMID- 15962014
TI  - Atypical glandular cells in cervical smear during pregnancy and postpartum
      period.

PMID- 15962015
TI  - Surveillance of above- and below-ground mosquito breeding habitats in a rural
      midwestern community: baseline data for larvicidal control measures against West
      Nile Virus vectors.
AB  - BACKGROUND: Mosquitoes in the genus Culex are thought to play a major role as
      vectors in the transmission cycle of West Nile virus (WNV) and other arboviruses
      in the United States. Effective control of mosquitoes through larviciding and
      adulticiding is expensive for communities and should be guided by reliable
      surveillance data on the distribution of mosquito breeding habitats. However, few
      small to medium sized cities in rural areas of the midwestern United States have
      this type of baseline information available. OBJECTIVE: During the summer of
      2004, we investigated the characteristics of Culex and other mosquito-breeding
      habitats in a rural central Wisconsin community with a population of
      approximately 19,000. Such baseline information will aid in the development of
      rational strategies to control mosquito populations and prevent human exposure to
      WNV and other mosquito-transmitted viruses. METHODS: Mosquito larvae were
      collected and identified weekly from 14 below-ground storm water catch basins and
      10 above-ground standing water sites distributed throughout the community.
      Collection began June 4, 2004 and continued through September 24, 2004. For each
      collection site the primary and adjacent land use patterns were determined.
      RESULTS: Over the study period, 1,244 larvae were collected from catch basins;
      94% were Culex species. Breeding activity was first detected in early July. Peak
      breeding was observed during a period of several weeks when average daily
      temperatures were at the maximum observed and rainfall had declined. Organically
      enriched catch basins in low intensity urban sites adjacent to forests and
      wetlands were found to be more productive breeding habitats compared to catch
      basins having little organic debris located in isolated high intensity urban
      sites. Above-ground standing water sites produced 1,504 larvae; 66% of which were
      Culex species. Flood control ditches and permanent wetlands with stagnant water
      were most productive, while ditches with moving water were least productive
      habitats. Larvae were produced earlier in the season by above-ground sites than
      were produced by catch basins. However, larvae production was more variable in
      above-ground sites since half the sites became dry at some point during the study
      period. CONCLUSION: The observed differences in Culex larvae production based on
      the variables of habitat-type, temperature, and precipitation support the need
      for ongoing surveillance in communities to guide public health officials in
      planning for and prioritizing mosquito control efforts.

PMID- 15962012
TI  - Adeno-associated virus vectors: potential applications for cancer gene therapy.
AB  - Augmenting cancer treatment by protein and gene delivery continues to gain
      momentum based on success in animal models. The primary hurdle of fully
      exploiting the arsenal of molecular targets and therapeutic transgenes continues
      to be efficient delivery. Vectors based on adeno-associated virus (AAV) are of
      particular interest as they are capable of inducing transgene expression in a
      broad range of tissues for a relatively long time without stimulation of a cell
      mediated immune response. Perhaps the most important attribute of AAV vectors is
      their safety profile in phase I clinical trials ranging from CF to Parkinson's
      disease. The utility of AAV vectors as a gene delivery agent in cancer therapy is
      showing promise in preclinical studies. In this review, we will focus on the
      basic biology of AAV as well as recent progress in the use of this vector in
      cancer gene therapy.

PMID- 15962016
TI  - Atypical Papanicolaou smear in pregnancy.
AB  - Atypical glandular cells (AGC) in Papanicolaou (Pap) smears can be associated
      with premalignant and malignant cervical and endometrial lesions. AGC is
      difficult to diagnose in pregnancy due to confusion with normal cellular changes
      that accompany graviditas. While guidelines have been established for management
      of AGC cases in the non-pregnant patient, special considerations are required
      when this is discovered during a pregnancy. A routine Pap smear performed on a 29
      year-old woman being seen for a history of infertility yielded AGC and a high
      grade squamous intraepithelial lesion. The patient achieved pregnancy 1 month
      later. Satisfactory colposcopic exam was performed with cytobrush sampling of the
      endocervical canal, in addition to 2 exocervical biopsies at 11 weeks gestation.
      Positive diagnosis of endocervical adenocarcinoma in situ resulted in a risk
      informed decision to proceed with a cold knife conization of the cervix. Final
      pathology showed complete resection of the lesion with negative margins and an
      additional area of squamous dysplasia (cervical intraepithelial neoplasia, grade
      II to III). Appropriate follow-up was recommended. AGC found upon Pap smear
      during a pregnancy can be associated with significant pathology for which an
      aggressive management approach is warranted.

PMID- 15962018
TI  - Controversies in off-pump coronary artery surgery.
AB  - Motivated by a desire to reduce the morbidity of a well-established and effective
      procedure for coronary artery disease, up to 25% of coronary artery bypass
      operations are being performed without the use of a heart-lung pump. Concerns
      remain about the quality of the coronary anastomoses and the completeness of
      revascularization. Randomized trials have not revealed the significant reduction
      in morbidity or mortality that the early enthusiasts had hoped for. Yet a number
      of non-randomized studies have shown clinical benefit from the avoidance of an
      extracorporeal circulation, but these have been criticized for potential bias in
      patient selection and management.A majority of surgeons have not yet adopted this
      technique and are waiting for the accumulation of more evidence.

PMID- 15962017
TI  - Self-measurement of blood pressure at home in the management of hypertension.
AB  - To be suitable for the management of hypertension, self-measurement of blood
      pressure (BP) at home should follow international recommendations. The use of
      accurate and validated measuring devices is an important prerequisite. Upper arm
      BP monitors are the first choice, while wrist and finger devices cannot be
      recommended. Measurements should, preferentially, be downloaded from the memory
      of a device or printed. Reference values have been proposed, but were mostly
      based on cross-sectional observations and have not yet been widely validated by
      prospective outcome studies. Currently, levels of home BP of <135 mm Hg systolic
      and 85 mm Hg diastolic are usually considered normal. Home BP measurement is
      sometimes recommended as an alternative to ambulatory BP monitoring to diagnose
      white-coat hypertension.However, home BP measurement cannot replace ambulatory BP
      monitoring in the diagnosis of hypertension (white-coat), but both techniques
      have complementary roles. The appropriateness of home BP measurement to guide
      antihypertensive treatment has only been tested in one large-scale randomized
      trial: the THOP (Treatment of Hypertension Based on Home or Office Blood
      Pressure) trial. The THOP trial showed that antihypertensive treatment based on
      home instead of office BP led to less intensive drug treatment, but also to less
      BP control with no differences in general wellbeing and left ventricular mass.
      Home BP monitoring also contributed to the identification of patients with white
      coat hypertension. On balance, most evidence supports the view that office BP
      measurement remains the key in the diagnosis and treatment of hypertension.
      Treatment can be started without confirmation of elevated office BP in patients
      with high office BP and target organ damage, or a high cardiovascular risk
      profile. In patients with raised office BP but without target organ damage (white
      coat hypertension), or with normal office BP but unexplained target organ damage
      (masked hypertension), ambulatory or home BP monitoring or both must be used to
      confirm the diagnosis. Few longitudinal studies have addressed the long-term
      prognostic meaning of home BP measurement. Until more prospective data become
      available, management of hypertension exclusively based on self-measurement of BP
      at home cannot be recommended.

PMID- 15962019
TI  - Auer rods galore! Acute promyelocytic leukemia.

PMID- 15962020
TI  - Antonio Maria Valsalva (1666 - 1723).

PMID- 15962021
TI  - Searching for evidence-based medicine in the literature part 2: resources.

PMID- 15962022
TI  - Insight into multiple sclerosis.

PMID- 15962023
TI  - A very short uranium-uranium bond: the predicted metastable U(2)2+.
AB  - Quantum chemical calculations, based on multiconfigurational wave functions and
      including relativistic effects, show that the U(2)2+ system has a large number of
      low-lying electronic states with S of 0 to 2 and Lambda ranging from zero to ten.
      These states share a very small bond length of about 2.30 A, compared to 2.43 A
      in neutral U2. The Coulomb explosion to 2 U+ lowers the energy by only 1.6 eV and
      is separated by a broad barrier.

PMID- 15962024
TI  - Characterisation of the water/o-nitrophenyl octyl ether system in terms of the
      partition of nonelectrolytes and of ions.
AB  - The Abraham linear free energy relationship, or solvation equation, has been
      applied to literature data on the partition of nonelectrolytes in the water to o
      nitrophenyl octyl ether (NPOE) system. The resulting equation is compared to
      equations for other water to solvent systems using the D-parameter of Abraham and
      Martins and the theta-parameter of Ishihama and Asakawa. It is shown that as a
      solvent in partitioning systems, NPOE quite resembles nitrobenzene and 1,2
      dichloroethane, and that the latter does not resemble an alkane-like solvent.
      Using descriptors for simple ions that we have previously obtained, we show that
      ions and nonelectrolytes can be included in the same linear free energy
      relationship.

PMID- 15962025
TI  - Prediction of collective diffusion coefficient of bovine serum albumin in aqueous
      electrolyte solution with hard-core two-Yukawa potential.
AB  - A new method to predict concentration dependence of collective diffusion
      coefficient of bovine serum albumin (BSA) in aqueous electrolyte solution is
      developed based on the generalized Stokes-Einstein equation which relates the
      diffusion coefficient to the osmotic pressure. The concentration dependence of
      osmotic pressure is evaluated using the solution of the mean spherical
      approximation for the two-Yukawa model fluid. The two empirical correlations of
      sedimentation coefficient are tested in this work. One is for a disordered
      suspension of hard spheres, and another is for an ordered suspension of hard
      spheres. The concentration dependence of the collective diffusion coefficient of
      BSA under different solution conditions, such as pH and ionic strength is
      predicted. From the comparison between the predicted and experimental values we
      found that the sedimentation coefficient for the disordered suspension of hard
      spheres is more suitable for the prediction of the collective diffusion
      coefficients of charged BSA in aqueous electrolyte solution. The theoretical
      predictions from the hard-core two-Yukawa model coupled with the sedimentation
      coefficient for a suspension of hard spheres are in good agreement with available
      experimental data, while the hard sphere model is unable to describe the behavior
      of diffusion due to its neglect of the double-layer repulsive charge-charge
      interaction between BSA molecules.

PMID- 15962026
TI  - A hierarchy of global coupling induced cluster patterns during the oscillatory H2
      electrooxidation reaction on a Pt ring-electrode.
AB  - We report experimental results on spatiotemporal pattern formation during the
      oscillatory hydrogen electrooxidation reaction on a Pt ring-electrode under
      negative (desynchronizing) global coupling (GC). Spatially one-dimensional
      profiles of the interfacial potential drop along the angular direction of the
      ring electrode are recorded by means of a potential probe. The dynamics is
      investigated as a function of two control parameters, the applied voltage U and
      the strength of the global coupling. The latter is adjusted either by varying the
      distance between the working electrode (WE) and the reference electrode (RE) or
      by inserting a negative impedance device in series with the WE. In the absence of
      global coupling, uniform oscillations were destabilized by migration coupling,
      and electrochemical turbulence developed at large values of U (H. Varela, C.
      Beta, A. Bonnefont and K. Krischer, Phys. Rev. Lett., 2005, 94, 174104; ).
      Already low global coupling strengths sufficed to suppress turbulence. Instead,
      regular two-phase clusters formed. At higher coupling strength, a second type of
      two-phase cluster was observed as well as two types of irregular cluster
      patterns, which were connected with an irregular motion of the cluster boundaries
      and the emergence and disappearance of clusters through splitting and merging of
      the boundaries, respectively. Upon increasing the coupling strength even further,
      five-phase clusters were stabilized and at the highest coupling strength applied
      the cluster patterns transformed into strongly modulated pulses. The two types of
      two-phase clusters and the five-phase clusters are analyzed employing several
      signal processing techniques.

PMID- 15962027
TI  - The nature of the oxidation states of gold on ZnO.
AB  - The interaction between gold in the 0, i, ii and iii oxidation states and the
      zinc-terminated ZnO(0001) surface is studied via the QM/MM electronic embedding
      method using density functional theory. The surface sites considered are the
      vacant zinc interstitial surface site (VZISS) and the bulk-terminated island site
      (BTIS). We find that on the VZISS, only Au(0) and Au(i) are stable oxidation
      states. However, all clusters of i to iii oxidation states are stable as
      substitutionals for Zn2+ in the bulk terminated island site. Au(OH)(x) complexes
      (x= 1-3) can adsorb exothermically onto the VZISS, indicating that higher
      oxidation states of gold can be stabilised at this site in the presence of
      hydroxyl groups. CO is used as a probe molecule to study the reactivity of Au in
      different oxidation states in VZISS and BTIS. In all cases, we find that the
      strongest binding of CO is to surface Au(i). Furthermore, CO binding onto Au(0)
      is stronger when the gold atom is adsorbed onto the VZISS compared to CO binding
      onto a gas phase neutral gold atom. These results indicate that the nature of the
      oxidation states of Au on ZnO(0001) will depend on the type of adsorption site.
      The role of ZnO in Au/ZnO catalysts is not, therefore, merely to disperse gold
      atoms/particles, but to also modify their electronic properties.

PMID- 15962028
TI  - Low temperature quantum rate coefficient of the H + CH+ reaction.
AB  - In this paper we report the first theoretical study of the title reaction. A
      global, single-valued model of the ground-state potential energy surface has been
      obtained by fitting to an extensive set of high-level ab initio calculations. The
      surface is found to be attractive apart from linear geometries where energy
      barriers appear due to conical intersections. This model was then used to
      calculate the reactive reactant state selected cross sections for collision
      energies ranging from threshold up to 4000 cm(-1). These calculations were
      performed using our version of the Baer's approach of the RIOSA-NIP method which
      is based on the use of a negative imaginary potential. We find that the reaction
      probability is extremely oscillatory as a function of kinetic energy as it is a
      case for insertion reactions with a low exoergicity. The resulting reaction rate
      coefficient is found to first increase slowly as a function of temperature up to
      a broad maximum around 20 K and then to decrease slowly when temperature keeps
      increasing.

PMID- 15962029
TI  - The influence of nuclear volume and electronic structure on the rotational energy
      of platinum monoxide, PtO.
AB  - The pure rotational spectra of seven isotopic species of platinum monoxide have
      been measured with a cavity pulsed jet Fourier-transform microwave spectrometer.
      The molecules were prepared by laser ablation of Pt foil in the presence of O2
      and stabilized in a supersonic jet of argon. A multi-isotopomer Dunham-type
      analysis of the spectra produced values for Y01 and Y11, along with unusually
      large values for Born-Oppenheimer breakdown (BOB) parameters for both Pt and O
      atoms. The values of the BOB parameters have been rationalized in terms of the
      molecular electronic structure and finite nuclear size (field shift) effects. A
      large negative 195Pt effective nuclear spin-rotation constant has been
      rationalized in terms of the electron-nucleus dipole-dipole hyperfine constant.
      Precise internuclear separations have been evaluated.

PMID- 15962030
TI  - The absorption spectrum of water near 750 nm by CW-CRDS: contribution to the
      search of water dimer absorption.
AB  - The absorption spectrum of natural water vapour around 750 nm has been recorded
      with a typical sensitivity of 3 x 10(-10) cm(-1) using a cw cavity ring down
      spectroscopy set up based on a Ti:sapphire laser. The 13 312.4-13 377.7 cm(-1)
      spectral interval was chosen as it corresponds to the region where water dimer
      absorption was recently measured (K. Pfeisticker et al., Science, 2003, 300, 2078
      2080). The line parameters (wavenumber and intensity) of a total of 286 lines of
      water vapor were measured by a one by one fit of the lines to a Voigt profile.
      For the main water isotopologue, 276 lines were measured with line intensities as
      weak as 5 x 10(-29) cm molecule(-1)i.e. about 50 times smaller than the weakest
      H(2)16O line intensities included in the 2004 edition of the HITRAN database. On
      the basis of the predictions of Schwenke and Partridge, all but 16 lines could be
      assigned to different isotopologues of water (H(2)16O, H(2)18O, and HD16O)
      present in natural abundance in the sample. A total of 272 energy levels of
      H(2)16O were determined and rovibrationally assigned to 18 upper vibrational
      states. Half of them had not been reported previously. The importance of the
      additional absorbance resulting from the observation of many new weak lines is
      discussed in relation to the detection of water dimer absorption and compared to
      the absorbance predicted by Schwenke and Partridge. The quality of the line
      parameters of water monomer is shown to be of crucial importance to identify the
      absorbance of the water dimer in the considered region.

PMID- 15962031
TI  - Dispersed fluorescence spectroscopy of the CBr2A1B1-X1A1 transition.
AB  - Dispersed fluorescence spectra following the excitation of the CBr2A1B1-X1A1 2
      and 2 bands at visible wavelengths were acquired in a discharge supersonic free
      jet expansion using an intensified charge-coupled device (ICCD) detector. The
      dispersed fluorescence spectra show signal-to-noise ratios of up to 60 and extend
      out to a maximum red shift frequency of 6000 cm(-1). Complete and detailed
      vibrational structure of the ground singlet state (X1A1) was observed.
      Vibrational parameters including fundamental frequencies, anharmonicities, and
      coupling constants were determined for the CBr2 X1A1 state. Additional
      vibrational structure starting at approximately 3650 cm(-1) was observed and this
      indicates the singlet-triplet energy gap to be >10 kcal mol(-1).

PMID- 15962032
TI  - Adding water to sugar: a spectroscopic and computational study of alpha- and beta
      phenylxyloside in the gas phase.
AB  - The gas phase structures of phenyl alpha- and beta-d-xylopyranoside (alpha- and
      beta-pXyl) and their mono-hydrates have been investigated using a combination of
      resonant two-photon ionization (R2PI), ultra-violet hole-burning and resonant
      infrared ion dip spectroscopy, coupled with density functional theory (DFT) and
      ab initio computation. The hole-burning experiments indicate the population of a
      single conformer only, in each of the two anomers. Their experimental and
      calculated infrared spectra are both consistent with a conformational assignment
      corresponding to the computed global minimum configuration. All three OH groups
      are oriented towards the oxygen atom (O1) on the anomeric carbon atom to form an
      all trans(ttt) counter-clockwise chain of hydrogen bonds. The mono-hydrates,
      alpha- and beta-pXyl(H(2)O) each populate two distinct structures in the
      molecular beam environment, with the water molecule inserted between OH4 and OH3
      or between OH3 and OH2 in alpha-pXyl(H2O), and between OH2 and O1 in either of
      two alternative orientations, in beta-pXyl(H2O). In all of the mono-hydrated
      xyloside complexes, the water molecule inserts into the weakest link of the sugar
      molecules' hydrogen-bonded chain of hydroxy groups, creating a single extended
      chain, strengthened by co-operativity. The all-trans configuration of the xylose
      moiety is retained and the mono-hydrate structures correspond to those calculated
      to lie at the lowest relative energies.

PMID- 15962033
TI  - Reaction dynamics of Y + O2--> YO(X,A',A)+ O(3P(J)) studied by the crossed-beam
      technique.
AB  - The dynamics of the reaction, Y + O2--> YO + O was studied by using the crossed
      beam technique at several collision energies from 10.3 to 52.0 kJ mol(-1). The Y
      atomic beam was generated by laser vaporization and crossed with the O2 beam at a
      right angle. Among the energetically accessible electronic states of YO, the
      formation of the A2Pi and A'2Delta states was observed by their chemiluminescence
      at all collision energies. By analyzing the chemiluminescence spectra of
      YO(A2Pi(1/2,3/2)-X2Sigma+), vibrational state distributions and relative
      populations of spin-orbit states were determined for YO(A2Pi(1/2,3/2)). At low
      collision energies, the vibrational distributions agree quite well with those
      expected from the statistical energy partitioning, while a little deviation from
      the statistical expectation was observed at the highest energy, 52.0 kJ mol(-1).
      The populations of two spin-orbit states are in good agreement with the
      statistical expectations at all collision energies. The vacuum ultraviolet laser
      induced fluorescence (VUV-LIF) technique was employed to determine the
      distributions of spin-orbit states of the product O(3P(J)) at two collision
      energies, 20.7 and 52.0 kJ mol(-1). The line shapes of the O atom transitions
      were analyzed to determine relative branching ratio of the ground state to the
      excited states of YO, i.e. YO(X2Sigma+)+ O(3P(J))vs. YO(A2Pi and A'2Delta)+
      O(3P(J)). The results showed that the electronically excited YO was formed with
      comparable amount with the ground state which is statistically more favorable,
      and suggested the occurrence of two mechanisms taking place in the title
      reaction.

PMID- 15962034
TI  - A kinetic study of the reactions of vanadium, iron, and cobalt with sulfur
      dioxide.
AB  - A kinetic study of the reactions of ground state V, Fe, and Co with SO2 is
      reported. V, Fe, and Co were produced by the 248 nm photodissociation of VCl4,
      ferrocene, and Co(C5H5)(CO)2, respectively, and were detected by laser-induced
      fluorescence. V + SO2 proceeds by an abstraction reaction with rate constants
      given by k=(2.33 +/- 0.57)x 10(-10) exp[-(1.14 +/- 0.19) kcal mol(-1)/RT] cm3
      molecule(-1) s(-1) over the temperature range 296-571 K. Fe + SO2 was studied in
      the N2 buffer range of 10-185 Torr between 294 and 498 K. The limiting, low
      pressure third-order rate constants are given by k(0)=(3.45 +/- 1.19)x 10(-30)
      exp[-(2.81 +/- 0.24) kcal mol(-1)/RT] cm6 molecule(-2) s(-1). Co + SO2 was
      studied in the CO2 buffer range of 5-40 Torr between 294 and 498 K. This reaction
      is independent of temperature over the indicated range and has a third-order rate
      constant of k0=(5.23 +/- 0.28)x 10(-31) cm6 molecule(-2) s(-1). Results of this
      work are compared to previous work on the Sc, Ti, Cr, Mn, and Ni + SO2 systems.
      The reaction efficiencies for the abstraction reactions depend on the ionization
      energies of the transition metal atoms and on the reaction exothermicities, and
      the reaction efficiencies of the association reactions are strongly dependent on
      the energies needed to promote an electron from a 4s2 configuration to a 4s1
      configuration.

PMID- 15962035
TI  - Rate coefficients for the OH + CFH2CH2OH reaction between 238 and 355 K.
AB  - The rate coefficient for the reaction OH + CFH2CH2OH --> products (k1) between
      238 and 355 K was measured using the pulsed laser photolysis-laser induced
      fluorescence (PLP-LIF) technique to be (5.15 +/- 0.88)x 10(-12) exp[-(330 +/-
      45)/T] cm3 molecule(-1) s(-1); k1(298 K)= 1.70 x 10(-12) cm3 molecule(-1) s(-1).
      The quoted uncertainties are 2sigma(95% confidence level) and include estimated
      systematic errors. The present results are discussed in relation to the measured
      rate coefficients for the reaction of OH with other fluorinated alcohols and
      those calculated using recently reported structure additivity relationships for
      fluorinated compounds (K. Tokuhashi, H. Nagai, A. Takahashi, M. Kaise, S. Kondo,
      A. Sekiya, M. Takahashi, Y. Gotoh and A. Suga, J. Phys. Chem. A, 1999, 103, 2664
      2672, ). Infrared absorption cross sections for CFH2CH2OH are reported and they
      are used to calculate the global warming potentials (GWP) for CFH2CH2OH of
      approximately 8, approximately 2, and approximately 1, respectively, for the 20,
      100 and 500 year horizons. A brief discussion of the atmospheric degradation of
      CFH2CH2OH is provided. It is concluded that CFH2CH2OH is an acceptable substitute
      for CFCs in terms of its impact on Earth's climate and the composition of the
      atmosphere. The room temperature rate coefficient for the reaction OH + CFH2CH2OH
      --> products (k10) was measured to be 3.26 x 10(-12) cm3 molecule(-1) s(-1), in
      good agreement with recent measurements from this laboratory.

PMID- 15962036
TI  - Gas-phase rate coefficients for the reactions of nitrate radicals with (Z)-pent-2
      ene, (E)-pent-2-ene, (Z)-hex-2-ene, (E)-hex-2-ene, (Z)-hex-3-ene, (E)-hex-3-ene
      and (E)-3-methylpent-2-ene at room temperature.
AB  - Rate coefficients for reactions of nitrate radicals (NO3) with (Z)-pent-2-ene,
      (E)-pent-2-ene, (Z)-hex-2-ene, (E)-hex-2-ene, (Z)-hex-3-ene, (E)-hex-3-ene and
      (E)-3-methylpent-2-ene were determined to be (6.55 +/- 0.78)x 10(-13) cm3
      molecule(-1) s(-1), (3.78 +/- 0.45)x 10(-13) cm3 molecule(-1) s(-1), (5.30 +/-
      0.73)x 10(-13) cm(3) molecule(-1) s(-1), (3.83 +/- 0.47)x 10(-13) cm(3) molecule(
      1) s(-1), (4.37 +/- 0.49)x 10(-13) cm(3) molecule(-1) s(-1), (3.61 +/- 0.40)x 10(
      13) cm3 molecule(-1) s(-1) and (8.9 +/- 1.5)x 10(-12) cm3 molecule(-1) s(-1),
      respectively. We performed kinetic experiments at room temperature and
      atmospheric pressure using a relative-rate technique with GC-FID analysis. The
      experimental results demonstrate a surprisingly large cis-trans(Z-E) effect,
      particularly in the case of the pent-2-enes, where the ratio of rate coefficients
      is ca. 1.7. Rate coefficients are discussed in terms of electronic and steric
      influences, and our results give some insight into the effects of chain length
      and position of the double bond on the reaction of NO3 with unsaturated
      hydrocarbons. Atmospheric lifetimes were calculated with respect to important
      oxidants in the troposphere for the alkenes studied, and NO3-initiated oxidation
      is found to be the dominant degradation route for (Z)-pent-2-ene, (Z)-hex-3-ene
      and (E)-3-methylpent-2-ene.

PMID- 15962037
TI  - Nitrogen dioxide multiphase chemistry: uptake kinetics on aqueous solutions
      containing phenolic compounds.
AB  - The uptake coefficients of NO2 on aqueous solutions containing guaiacol, syringol
      and catechol were determined over the pH range from 1 to 13 using the wetted wall
      flowtube technique. The measured uptake coefficients were used to determine the
      rate coefficients for the reaction of the physically dissolved NO2 with the
      neutral and deprotonated forms of phenolic compounds listed above. These organic
      compounds are ubiquitous not only in biomass burning plumes but also in soils,
      where they form part of the building blocks of humic acids. The NO2 uptake
      kinetics on solutions containing guaiacol, syringol or catechol were observed to
      be strongly pH dependent with uptake coefficients increasing from below 10(-7),
      under acidic conditions, to more than 10(-5) at pH values above 10. This
      behaviour illustrates the difference of reactivity between the neutral phenolic
      species and the phenoxide ions. The corresponding second order rate coefficients
      were typically observed to increase from 10(5) M(-1) s(-1) for the neutral
      compounds to a minimum of 10(8) M(-1) s(-1) for the phenoxide ions.

PMID- 15962038
TI  - Depth profiling of sterically-stabilised polystyrene nanoparticles using laser
      ablation/ionisation mass spectrometric methods.
AB  - An aerodynamic lens has been used to introduce polystyrene nanoparticles into an
      apparatus that combines laser vaporisation with mass spectrometric measurements
      of ion intensity. The particles have a mean diameter of 129 nm and are sterically
      stabilised with poly(ethylene glycol) which coats the surface to a depth of
      approximately 5 nm. Measurements have been made at wavelengths of 266, 355, and
      523 nm, and over a range of laser powers. The results provide clear evidence that
      depth profiling can be achieved by changing the wavelength of the ablating
      radiation, but that changes in power at a single wavelength have little influence
      on the range of ions observed. At 523 nm the mass spectra are predominantly
      derived from surface-bound material, whilst at 266 nm the dominant contribution
      is from ions related to the polystyrene core of the particles. It is proposed
      that these differences in behaviour can be equated with existing models of the
      laser ablation process.

PMID- 15962039
TI  - A reexamination of the adsorption of CO and nitriles on alkali-metal mordenites:
      characterization of multiple interactions.
AB  - The low temperature adsorption of CO and the room temperature adsorption of
      propionitrile and ortho-toluonitrile on LiMOR, NaMOR, KMOR and CsMOR zeolites
      have been investigated by FT-IR spectroscopy. Two different CO species, both most
      probably located in the main channels coordinated on Na ions at IV and VI sites,
      have been observed. They are associated to a shift of the CO stretching to higher
      frequencies, as usual. However, together, more strongly bonded species associated
      to a slight shift of the CO stretching to a lower frequency are also observed.
      Similar species, with the CN stretching shifted upwards (weaker adsorption) and
      with the CN stretching shifted downwards (stronger adsorption) are also observed
      in the case of the interaction of propionitrile (PrN), a molecule that should
      enter the main channels, and in the case of the interaction of ortho-toluonitrile
      (o-TN), whose access to the main channels should be highly hindered. The data
      show that the species characterized by a stronger adsorption but a lower
      stretching frequency may form both in the main channels and at the external
      surface. Their formation is easier with the larger cations. These species are
      identified as "multiply bonded", possibly to two cations. The evidence for this
      new interaction, stronger than the usual one site-one molecule species, may
      change considerably the view of the adsorption chemistry of cationic zeolites,
      from localized simple sites to cooperative complex interactions.

PMID- 15962040
TI  - Polyhedra in (inorganic) chemistry.
AB  - A systematic description of polyhedra with varying degrees of regularity is
      illustrated with examples of chemical structures, mostly from different fields of
      Inorganic Chemistry. Also the geometrical relationships between different
      polyhedra are highlighted and their application to the analysis of complex
      structures is discussed.

PMID- 15962041
TI  - Easy hydrolysis of white phosphorus coordinated to ruthenium.
AB  - The P4 molecule bound to ruthenium as an eta1-ligand in [CpRu(PPh3)2(eta1-P4)]Y
      (Y = PF6, CF3SO3) undergoes an easy reaction with water in exceedingly mild
      conditions to yield PH3, which remains coordinated to the [CpRu(PPh3)2] fragment,
      and oxygenated derivatives.

PMID- 15962042
TI  - Stabilising small clusters: synthesis and characterisation of thermolabile
      [Gd4F7(15-crown-5)4][AsF6]5.6 SO2.
AB  - Addition of 15-crown-5 to [GdF(AsF6)2], both dissolved in liquid SO2, and
      crystallisation at -30 degrees C has led to the isolation of the tetranuclear
      ionic complex [Gd4F7(15-crown-5)4][AsF6]5.6 SO2 which is stable up to--10 degrees
      C where SO2 loss leads to loss of crystallinity.

PMID- 15962043
TI  - I...pi halogen-bonding in the structures of platinum-alkynyl compounds: an
      overlooked supramolecular interaction.
AB  - The crystal structures of both a symmetric and an unsymmetric platinum--alkynyl
      compound with terminal iodophenyl functionalities have been determined, and found
      to exhibit an attractive interaction between the iodine atom and the carbon
      carbon triple bond of the alkynyl ligand.

PMID- 15962044
TI  - Solid state coordination chemistry of the copper(ii)-terpyridine/oxovanadium
      organophosphonate system: hydrothermal syntheses, structural characterization and
      magnetic properties.
AB  - The hydrothermal reactions of CuSO4.5H2O, Na3VO4, 2,2':6':2''-terpyridine
      (terpy), and the appropriate organophosphonate ligand yield a series of materials
      of the Cu(ii)-terpy/oxovanadium organophosphonate family. The complexes exhibit
      distinct structures spanning one-, two- and three-dimensions and exhibiting
      diverse oxovanadium building blocks. Thus, [{Cu(terpy)}(V2O4)(O3PPh)(HO3PPh)2]
      (1) is one-dimensional and constructed from binuclear units of corner-sharing
      V(v) square pyramids. While [{Cu(terpy)}VO(O3PCH2PO3)] (2),
      [{Cu(terpy)}2(V4O10)(O3PCH2CH2PO3)] (3), and
      [{Cu(terpy)}(V2O4){O3P(CH2)3PO3}].2.5H(2)O (4.2.5H2O) are similarly one
      dimensional, the V/O structural components consist of isolated V(iv) square
      pyramids, tetranuclear V(v) units of three tetrahedra and one square pyramid in a
      corner-sharing arrangement, and isolated V(v) tetrahedra and square pyramids,
      respectively. The second propylenediphosphonate derivative,
      [{Cu(terpy)}(V2O4){O3P(CH2)3PO3}] (5) is three-dimensional and exhibits isolated
      V(v) tetrahedra as the vanadate component. The two-dimensional structure of
      [{Cu(terpy)(H2O)}(V3O6){O3P(CH2)4PO3}] (6) is mixed valence with isolated V(iv)
      square pyramids and binuclear units of corner-sharing V(v) tetrahedra providing
      the V/O substructures.

PMID- 15962045
TI  - DFT calculations, structural and spectroscopic studies on the products formed
      between IBr and N,N'-dimethylbenzoimidazole-2(3H)-thione and -2(3H)-selone.
AB  - The NBO charge distribution calculated at DFT level on the [LEX](+) species
      [LE=N,N'-dimethylbenzoimidazole-2(3H)-thione (3) and -2(3H)-selone (4)(Scheme 1);
      X=I, Br] suggests that the most likely products from the reaction 3 of 4 and with
      IBr are the 10-X-2 charge-transfer (CT) adduct and the 10-Se-3 "T-shaped"
      hypervalent adduct featuring a linear Br--Se--I system, respectively. This
      prediction is confirmed by the synthesis, and X-ray diffraction analysis of 3.IBr
      (I) and 4.I(0.72)Br(1.28)(II). In particular II, is a 10-Se-3 "T-shaped"
      hypervalent adduct containing an almost linear X--Se--X system [X--Se--X
      179.07(3) degrees, X=I(0.36)/Br(0.64)], which is roughly perpendicular to the
      average plane of the benzoimidazole moiety. The FT-Raman spectra of I and II
      agree very well with their structural features. In particular, the complexity of
      the FT-Raman spectrum of II reflects the disorder in the X-ray crystal structure
      of this compound.

PMID- 15962046
TI  - Formation of [2 + 2] diruthenium(II) metallomacrocycles from ligands containing
      2,2':6',2''-terpyridine domains linked through flexible polyethyleneoxy spacers.
AB  - The syntheses of three ligands containing two terpy metal-binding domains linked
      through flexible polyethyleneoxy spacers are described. These ligands have been
      utilised as building blocks in a two-step process for the formation of a series
      of dinuclear ruthenium(II) metallomacrocycles of the type [Ru2L2]4+. Employing a
      two-step methodology allows the formation of homoleptic ([Ru2L2]4+) and
      heteroleptic ([Ru2LL']4+) species in which the ligands differ in the length of
      the polyethyleneoxy spacer connecting each terpy motif. Homoleptic
      metallomacrocycles have been characterised through single crystal X-ray
      diffraction studies, while 2D-NMR spectroscopy has been employed for the
      characterisation of the heteroleptic species.

PMID- 15962047
TI  - Coordination chemistry of P, O-bidentate phosphinophenolates with Ga3+ and In3+.
AB  - Novel complexes of Ga3+ and In3+ were synthesized with two hetero donor
      phosphinophenolate ligands (PO-, ortho-phenoxydiphenylphosphine; MePO-, 5-methyl
      2-phenoxydiphenylphosphine). RPO-(R=H, Me) binds in a bidentate fashion through
      both the hard O and the soft P donor atoms to In3+, whereas, it only binds Ga3+
      through the O donor. Electrochemical synthesis proved to be a practical synthetic
      approach to In2(PO)3Cl3, In(PO)3 and In(MePO)3. [In(MePO)(H2O)Cl2]2 and
      Ga(HPO)Cl3 were synthesized from MCl3(M=In and Ga, respectively). Both dimetallic
      indium complexes, [In(MePO)(H2O)Cl2]2 and In2(PO)3Cl3, incorporate phenolate
      oxygen atoms bridging the two metal ions. Each pair of In atoms are in a
      distorted octahedral geometry in each complex, with the former complex having a
      coordination sphere of PO3Cl2 for both indium metal ions and the latter showing a
      coordination sphere of PO3Cl2 for one indium and P2O3Cl for the other. Ga(HPO)Cl3
      is a zwitterionic complex, with Ga having a OCl3 coordination core. All these
      complexes were fully characterized by a variety of techniques including X-ray
      crystallography.

PMID- 15962048
TI  - Synthesis, structure, and reactivity of fluorous phosphorus/carbon/phosphorus
      pincer ligands and metal complexes.
AB  - Reactions of the diphosphine 1,3-C6H4(CH2PH2)2 and fluorous alkenes
      H2C=CHR(fn)(R(fn)=(CF2)(n-1)CF3; n = 6, 8) at 75 degrees C in the presence of
      AIBN give the title ligands 1,3-C6H4(CH2P(CH2CH2R(fn))2)2(3-R(fn)) and byproducts
      1,3-C6H4(CH3)(CH2P(CH2CH2R(fn))2)(4-R(fn)) in 1 : 3 to 1 : 5 ratios. Workups give
      -R(fn) in 4--17% yields. Similar results are obtained photochemically. Reaction
      of 1,3-C6H4(CH2Br)2 and HP(CH2CH2R(f8))2 (5) at 80 degrees C (neat, 1 : 2 mol
      ratio) gives instead of simple substitution the metacyclophane [1,3
      C6H4(CH2P(CH2CH2R(f8))2 CH2-1,3-C(6)H(4)CH(2)P[lower bond 1
      end](CH2CH2R(f8))2C[upper bond 1 end]H2](2+)2Br-, which upon treatment with
      LiAlH(4) yields 3-R(f8)(20%), 4-R(f8), and other products. Efforts to better
      access 3-R(f8), either by altering stoichiometry or using various combinations of
      the phosphine borane (H3B)PH(CH2CH2R(f8))2 and base, are unsuccessful. Reactions
      of 3-R(fn) with Pd(O2CCF3)2 and [IrCl(COE)2]2(COE=cyclooctene) give the palladium
      and iridium pincer complexes (2,6,1-C6H3(CH2 P(CH2CH2R(fn))(2)(2)Pd(O2CCF3)(10
      R(fn); 80-90%) and (2,6,1-C6H3(CH2P(CH2CH2R(f8))2)2)Ir(Cl)(H)(11-R(f8); 29%),
      which exhibit CF3C6F(11)/toluene partition coefficients of >96 : <4. The crystal
      structure of 10-R(f8) shows CH2CH2R(f8) groups with all-anti conformations that
      extend in parallel above and below the palladium square plane to create fluorous
      lattice domains. NMR monitoring shows a precursor to 11-R(f8) that is believed to
      be a COE adduct.

PMID- 15962049
TI  - Dative sigma- and pi-bonding in boron-nitrogen compounds: molecular structures of
      (CH3)2NB(CH3)N(CH3)B(CH3)2 and [(CH3)2B]2NN(CH3)2 determined by gas electron
      diffraction and quantum chemical calculations.
AB  - The molecular structures of
      dimethylamino[(dimethylboryl)methylamino]methylborane, Me2NBMeNMeBMe2 (1) and 1,1
      bis(dimethylboryl)-2,2-dimethylhydrazine, (Me2B)2NNMe2 (2) have been determined
      by gas electron diffraction (GED), density functional theory calculations at the
      B3PW91/6-311++G** level and ab initio calculations at the MP2/6-311++G** level. 1
      adopts an open structure similar to that of the isoelectronic hydrocarbon
      molecule permethylbutadiene; the central B-N bond distance at 148.0/149.3(7) pm
      (MP2/GED) corresponds to a single covalent N--B bond distance, the two terminal
      distances, 140.9/140.5(4) pm and 141.8/141.3(4) pm, correspond to the distance
      between N and B atoms joined by a covalent sigma-bond and a dative pi-bond. A
      closed form where the establishment of a dative bond between the terminal N and B
      atoms has led to the formation of a four-membered ring also corresponds to a
      minimum on the potential energy surface, but the energy is calculated to be 14.3
      kJ mol(-1) higher at the MP2 level. This structure is also incompatible with the
      GED data. 2 adopts a structure in which a dative sigma-bond between the
      dimethylamino N atom and one of the boron atoms has led to the formation of a
      three-membered N(2)B ring. The dative sigma-bond distance is 165.5/164.0(13) pm,
      the two other bond distances in the ring are N-B=150.6/148.9(9) pm corresponding
      to a covalent sigma-bond and N-N=145.1/145.4(3) pm. The terminal B--N distance
      139.6/138.9(9) pm is consistent with a covalent sigma-bond augmented by a dative
      pi-bond. An open Y-shaped structure also corresponds to a minimum on the
      potential energy surface, but the energy is 18.7 kJ mol(-1) higher (MP2) and it
      is incompatible with the GED data.

PMID- 15962050
TI  - The experimental gas-phase structures of 1,3,5-trisilylbenzene and
      hexasilylbenzene and the theoretical structures of all benzenes with three or
      more silyl substituents.
AB  - The structures of 1,3,5-trisilylbenzene and hexasilylbenzene in the gas phase
      have been determined by electron diffraction, and that of 1,3,5-trisilylbenzene
      by X-ray crystallography. The structures of three trisilylbenzene isomers, three
      tetrasilylbenzenes, pentasilylbenzene and hexasilylbenzene have been computed, ab
      initio and using Density Functional Theory, at levels up to MP2/6-31G*. The
      primary effect of silyl substituents is to narrow the ring angle at the
      substituted carbon atoms. Steric interactions between silyl groups on
      neighbouring carbon atoms lead first to displacement of these groups away from
      one another, and then to displacement out of the ring plane, with alternate
      groups moving to opposite sides of the ring. In the extreme example,
      hexasilylbenzene, the SiCCSi dihedral angle is 17.8(8) degrees .

PMID- 15962051
TI  - Functionalised trimethylsilyl reagents in cluster synthesis: reactions of
      Ph2P(S)SSiMe3 with group 11 salts.
AB  - A series of complexes, ranging from the small cluster
      1/infinity[Ag(Ph2PS2)(dppe)](infinity) [dppe=1,2-bis(diphenylphosphino)ethane] to
      [Cu48S20(O(t)Bu)2(Ph2PS2)2(dppm-)4(dppm)4][dppm=1,2
      bis(diphenylphosphino)methane] (the largest Cu cluster containing
      phosphinodithioato ligands), has been synthesised. The structural evidence
      presented here indicates that in these reactions initially small cyclic
      aggregates or one-dimensional coordination polymers are formed. The growth of
      these intermediates to larger aggregates can take up to several months and could
      proceed via cationic intermediates.

PMID- 15962052
TI  - Racemic monoperoxovanadium(V) complexes with achiral OO and ON donor set
      heteroligands: synthesis, crystal structure and stereochemistry of
      [NH3(CH2)2NH3][VO(O2)(ox)(pic)].2H2O and [NH3(CH2)2NH3][VO(O2)(ox)(pca)].
AB  - Monoperoxovanadium(V) complexes, [NH3(CH2)2NH3][VO(O2)(ox)(pic)].2H2O (1) and
      [NH3(CH2)2NH3][VO(O2)(ox)(pca)] (2) [NH3(CH2)2NH3 = ethane-1,2-diammonium(2+),
      ox=oxalate(2-), pic=pyridine-2-carboxylate(1-), pca=pyrazine-2-carboxylate(1-)],
      were synthesized and characterized by X-ray analysis, IR and Raman
      spectroscopies. The five equatorial positions of the pentagonal bipyramid around
      the vanadium atoms are occupied by the eta2-peroxo ligand, two oxygen atoms of
      the ox, and the nitrogen atom of the pic or pca ligands, respectively. The oxo
      ligand and the oxygen atom of pic or pca are in the axial positions. Networks of
      X-HO (X=C, N or O) hydrogen bonds, and pi-pi interactions between aromatic rings
      in and anion-pi interactions in , determine the molecular packings and build up
      the supramolecular architecture. Three stereochemical rules for occupation of the
      donor sites in two-heteroligand [VO(O2)(L1)(L2)] complexes (L1, L2 are bidentate
      neutral or differently charged anionic heteroligands providing an OO, NN or ON
      donor set) are discussed. and crystallize as racemic compounds. The 51V NMR
      spectra proved that the parent complex anions of and partially decompose on
      dissolution in water to the monoperoxo-ox, -pic or -pca complexes.

PMID- 15962053
TI  - Enantioselectivity in Ni(II) Schiff-base complexes derived from amino-acids and
      (S)-o-N-(N-benzylprolyl)aminobenzophenone: molecular structure of several chiral
      Ni(II) Schiff-base complexes, circular dichroism and molecular mechanics studies.
AB  - Several Ni(II) complexes derived from (S)-o-N-(N-benzylprolyl)aminobenzophenone
      ((S)-BBP) and amino acids of general formula [Ni((S)-BBP-L-(or D-)-aa)] were
      prepared. The crystal and molecular structures of [Ni((S)-BBP-Gly)], [Ni((S)-BBP
      L-Ser)] and [Ni((S)-BBP-L-aaIm)](aaIm =L-2-amino-3-(imidazol-1-yl)propanoate were
      determined by X-ray diffraction analysis. In the three complexes the nickel atoms
      display a square-planar coordination and the overall structure around the metal
      indicates that the entire Schiff-base ligands form quite rigid frameworks.
      Molecular mechanics calculations were carried out for complexes [Ni((S)-BBP
      Gly)], [Ni((S)-BBP-Ser)] and [Ni((S)-BBP-aaIm)] containing either the L- or D
      amino acid forms, and the factors controlling the stereoselectivity are
      discussed. Several other [Ni((S)-BBP-L-aa)] complexes are also prepared and their
      circular dichroism spectra in solution and of the solids dispersed in KBr disks
      are measured and discussed. In agreement with other studies in solution with
      similar [Ni((S)-BBP-aa)] complexes, the Cotton effects for the bands with
      lambda(max) at 520--530 nm are positive when the amino acids have the L
      configuration at the alpha-carbon. The same is observed in this work for the
      solid-state CD spectra of all compounds.

PMID- 15962054
TI  - Magneto-structural correlations in binuclear copper(II) compounds bridged by a
      ferrocenecarboxylato(-1) and an hydroxo- or methoxo-ligands.
AB  - The syntheses, characterization and X-ray crystal structures of the first two
      examples of asymmetrically bridged dinuclear copper(ii) complexes containing a
      ferrocenecarboxylato ligand and a methoxo group in [{Cu(dmen)}2(micro-OMe){micro
      O2C(eta5-C5H4)Fe(eta5-C5H5)}](ClO4)2, 1, (dmen=N,N-dimethylethylenediamine) or an
      hydroxo group in [{Cu(tmen)}2(micro-OH){micro-O2C(eta5-C5H4)Fe(eta5
      C5H5)}](ClO4)2, 2 , (tmen=N,N,N'N'-tetramethylethylenediamine) are reported.
      Magneto-chemical studies revealed that 1 and 2 exhibit opposite superexchange
      interactions between the two Cu(II) paramagnetic centers: an antiferromagnetic
      coupling (J = -11 cm(-1)) in 1 and a ferromagnetic interaction (J = +29 cm(-1))
      in 2. The results obtained from these studies suggest that the weak interactions
      between the Cu(II) ions and the perchlorate anions detected in the crystal
      structures are important to introduce significant distortions in the
      heterobridged [Cu2(micro-OR){micro-O2C(eta5-C5H4)Fe(eta5-C5H5)}]2+ cores of 1 and
      2, which clearly affect the nature and strength of the superexchange
      interactions. Computational studies based on density functional theory and ab
      initio multiconfigurational second-order perturbation theory (CASPT2)
      calculations have also been performed in order to rationalize the magnetic
      behaviour of 1 and 2. The magneto-structural correlations for complexes
      containing the [Cu(micro-OR)(micro-O2CR')Cu] core are discussed, and the
      relevance of the out-of-plane angle of the R group with the Cu(micro-OR)Cu plane
      established.

PMID- 15962055
TI  - Cultivating the art of service.

PMID- 15962056
TI  - [Quality of life and depressive symptoms in nursing residents].
AB  - This study aimed to evaluate quality of life and prevalence of
      dysphoria/depressive symptoms in nursing residents at a medical school in Sao
      Paulo, Brazil. An exploratory, descriptive and cross-sectional study was carried
      out, involving 68 nursing residents from the first and second year of residency
      from all specialty areas, by applying the Brazilian version of the quality of
      life questionnaire SF-36 (Medical Outcomes Study 36--Item Short-Form Health
      Survey) and the Brazilian Version of the Beck Depression Inventory (BDI). Aspects
      related to quality of life were at risk in the mental component of SF-36:
      emotional aspects, vitality and mental health. Dysphoria/depression were found in
      27.9% of the nursing residents.

PMID- 15962057
TI  - [Difficulties experienced by the patient care team at the intensive care unit].
AB  - This interpretative case study aimed to identify the difficulties experienced by
      the patient care team while working at the Intensive Care Unit. Data were
      collected through participant observation and semistructured interviews with
      doctors, nurses and nurse's aides. Two major categories emerged from the data
      analysis: Care delivery in intensive care-- "it is difficult to deal with death
      and inform the patient's family" and care delivery in intensive care-- "the lack
      of material resources and the difficulty to work in a team". The difficulties are
      related to the contact with family members, dealing with death and the lack of
      material resources, and particularly with the relation between team members.
      Therefore, teams need to promote opportunities and discussions to reflect on the
      technical, scientific and ethic aspects of care for critical patients as well as
      family members, with a view to better care quality and interpersonal relations.

PMID- 15962058
TI  - [Team mourning: revelations of nursing professionals on the care provided to
      children/adolescents in the process of death/dying].
AB  - For nursing professionals, death is the greatest villain of their work since, in
      general, they are educated to take care of life only. The purpose of this study
      is to investigate how nursing professionals experience mourning when facing the
      death of hospitalized children/adolescents. Therefore, authors used a qualitative
      descriptive-exploratory research. Data were collected through interviews with
      nursing professionals who work in clinics with pediatric beds at a university
      hospital. Empirical data showed that professionals need emotional support in
      order to experience mourning and prevent the Burnout Syndrome. Authors recommend
      the inclusion of the theme death in the curricula, and also that hospitals must
      turn to permanent education as a strategy to promote changes in attitudes and
      behaviors regarding patients who are dying.

PMID- 15962059
TI  - [Nursing: the meaning of this profession to nurses. A first approach].
AB  - In an attempt to understand, tell and, why not, participate a little in the
      history of Nursing, we proposed to study the prejudices and negative stereotypes
      that have permeated this profession over time. This is a before-after
      experimental type of study in a population of adolescents regularly enrolled in
      the eleventh grade of a Brazilian public school. The intervention took the form
      of a lecture about the profession and a questionnaire with closed questions which
      was applied before and after the lecture. Conclusions were based on the results
      of binomial and McNemar's non-parametric tests for the significance of changes.
      Although the statistically significant presence of prejudice and negatives
      stereotypes was not found, the results of the intervention were in line with
      expectations, since the changes(or tendency towards changes) took place exactly
      in those subgroups that showed a greater frequency of stereotypes.

PMID- 15962060
TI  - [Teaching of nursing in mental and psychiatric health: the point-of-view of
      teachers and students in a social phenomenology perspective].
AB  - This study aimed to understand the teaching-learning process from the point-of
      view of teachers and students who experienced the nursing practice in mental and
      psychiatric health. Data were collected through interviews with students and
      teachers who had experienced the phenomenon and analyzed according to a social
      phenomenology perspective. The teachers' experiences gave rise to the following
      concrete meaning categories: valuing communication and the relation between
      persons, learning to appreciate others as human beings, appreciating integral
      care; demystifying fears and prejudices and attaching meaning to self-knowledge.
      The following categories emerging from students' interviews: acknowledging the
      relevance of knowledge in communication and interpersonal relations; learning to
      appreciate others as human beings; applying acquired knowledge to integral care;
      feeling motivated to change attitudes; acknowledging the meaning of self
      knowledge. Finally, the social types were described. In this subject, the
      teaching-learning process arouses interest in the specialty, personal development
      and valuation of its application in general nursing.

PMID- 15962061
TI  - [Production of meanings about family members living with mentally-ill patients].
AB  - Nowadays, family care is a great challenge for Mental Health practice, which
      requires professionals to study and take a closer look at these social actors.
      This study, which is guided by a social constructionist and qualitative approach,
      aimed to get to know the meanings Family Health Program (FHP) professionals
      attribute to family members living with mentally-ill patients. Data were
      collected by means of the focus group technique, involving members from two FHP
      teams in Ilheus/Bahia, Brazil. As a result, we describe the family members and
      their conceptual registers, as well as the following meanings: caring, motivating
      and suffering prejudice; powerless and lacking resources; producing abuse and
      unbalanced. It was observed that some of these meanings reinforce the community's
      exclusion of mental patients and their family members, while others oppose this
      discourse and are thus able to favor a closer approximation between these actors
      and the professionals, in view of a new practice that improves their living
      conditions.

PMID- 15962062
TI  - [The role of visiting family member and companion of adult and elderly people
      according to nurse indications].
AB  - This qualitative study was based on Symbolic Interactionism and Grounded Theory
      and aimed to understand the interactive experience of visiting family members and
      companions of hospitalized adult and elderly people and to develop a theoretical
      model of this experience. Data were collected through observations and
      interviews. Two phenomena emerged from the data analysis: living the expectation
      of hospitalization and assuming the roles of a family visitor or companion.
      Understanding this experience increased our knowledge about the change that
      occurred, which was called "shifting between the role of visiting family member
      and companion in view of nurses' indications": sharing an experience of few
      pleasures in solidarity with hospitalized adult and elderly people.

PMID- 15962063
TI  - [Investment of time resource in prenatal care by family health staff].
AB  - This study is about low-risk pregnant women attended by a family health unit. It
      aims to describe the time resource the health staff invested and to analyze its
      configuration in the prenatal monitoring process. Data were collected from 47
      women between 20 and 29 years old, who were attended from 2001 to 2003, in the
      eastside of Sao Paulo City. The pregnant women were classified according to the
      health care they received: a first group without health problems, a second with
      early expert intervention and a third with patients needing dental treatment. In
      the three groups, more time was invested by health professionals with higher
      education, followed by community health agents during home visits. Average total
      time per pregnant woman was 10 hours for the first group and 12 hours for the
      second and the third group. The time invested in direct care ranged from 59.40%
      to 80.51%.

PMID- 15962064
TI  - [The contribution of a scientific journal to nursing integration and the
      foundation of professional actions].
AB  - This study analyzes how the Latin American Journal of Nursing contributed to the
      integration of nurses in Brazil and Latin America and provided foundations for
      their professional actions. The research methodology is based on the knowledge
      management model called "Knowledge Capitals", developed by the CRIE (Business
      Intelligence Reference Center), which focuses on subscriber Relationship Capital.
      Data were collected from the Journal's subscriber database and by means of an
      electronic questionnaire sent to subscribers ranked as "private persons" and
      those with an electronic address. It was evidenced that the Journal's role is
      inexpressive in Latin America, with a merely satisfactory penetration in Brazil.
      The respondents confirmed the Journal's contribution to the foundation of
      professional nursing actions.

PMID- 15962065
TI  - [Post-hemorrhoidectomy pain descriptors].
AB  - This study aimed at comparing scales of judgements on differences and verifying
      the stability and agreement of the estimation made by descriptors of post
      operative pain as assessed by three different samples. Nineteen subjects who had
      been submitted to hemorrhoidectomy participated in the study. They were randomly
      divided into three groups (Group C, T and F), who received an intravenous
      administration of ketoprofen 100 mg, tenoxicam 40 mg or physiological serum 0.9%
      before the surgery. The task of each participant was to assign a score, from 1 to
      7, to each descriptor of the pain felt in the first complaint after surgery. The
      descriptors attributed to post-operative pain were evaluated by the
      psychophysical method of category estimation. The obtained results were: the
      descriptors with higher scores for Group C were intense, unbearable and terrible;
      for Group T, intense, tremendous and unbearable and for Group F, unbearable,
      intense and terrible.

PMID- 15962066
TI  - [Nursing care in ambulatory surgery at a teaching hospital: patients, procedures
      and biological and psychosocial needs].
AB  - This descriptive study aimed to characterize the profile of 167 subjects who were
      treated at the Ambulatory Surgical Center of a University Hospital in Sao Paulo
      State and procedures realized at the Ambulatory Surgical Center, as well as to
      identify the biological and psychosocial needs of these patients. Data were
      obtained through a semistructured interview and patients' files and were subject
      to descriptive analysis. The group was characterized by an equal number of
      individuals from both genders; average age was 51 years and socioeconomic levels
      were poor. The most common surgical and anesthetic procedures were ophthalmologic
      procedures and use of local anesthesia with or without sedation. The biological
      needs were: altered arterial pressure, electrocardiographic alterations, use of
      medication, allergy to medication, prolonged fasting, nausea, vomiting and pain.
      The psychosocial needs were: worry, fear, anxiety, discomfort caused by waiting
      for the realization of procedures and doubts or lack of information concerning
      perioperative care.

PMID- 15962067
TI  - [The sickening process of colostomy patients by cancer].
AB  - This study aimed to understand how patients with colostomy by cancer and their
      family members perceive the sickening process. The theoretical and methodological
      reference frameworks the study was based on were anthropology and ethnography.
      Data were collected through interviews, in a narrative form, and observations
      with twelve colostomy patients and five family members, in the period from June
      2002 to May 2003. The analysis allowed us to understand that the experience of
      having a colostomy by cancer is a social-cultural construction.

PMID- 15962068
TI  - [Corticotrophin hormone serum levels of parturients submitted to nonpharmacologic
      anxiety and pain relief method during labor].
AB  - This study aimed to analyze the plasma ACTH levels and the correlation between
      the ACTH levels and pain and anxiety during parturition. Seventeen parturients
      received routine nursing care (control group--CG) and nineteen (Experimental
      Group--EG) were stimulated and guided to perform respiration and relaxation
      techniques. ACTH levels, pain intensity and state-trait anxiety were evaluated.
      ACTH levels were lower at the beginning of labor, peaked at the end and decreased
      again in the immediate postpartum period. There was no significant statistical
      difference between the groups. Lower ACTH levels and partial stress relief in the
      EG suggest the interference of breathing and relaxation techniques; ACTH levels
      did not show any correlation with anxiety or pain in any of both groups.

PMID- 15962069
TI  - [Greater survival among patients with immunogenetic markers of rapid progression
      to AIDS: subsidies for nursing care].
AB  - This study sought subsidies for improving nursing care programs for AIDS patients
      and aimed to verify the influence of changes in sexual behavior, including the
      adoption of safe sex practices, associated with the survival of AIDS patients
      with immunogenetic markers of rapid disease progression. 27 AIDS patients were
      interviewed, with genetic predisposition to rapid progression to AIDS. Genes were
      typified through the polymerase chain reaction. In spite of the presence of
      immunogenetic factors, associated with individual predisposition to a rapid
      evolution of the disease, changes in sexual behavior, including safe sex
      practices and antiretroviral therapy, may be related to greater survival. This
      suggests that counseling, detection of risk attitudes and health education,
      focusing on positive health behavior, are tools nursing must use with HIV
      positive patients, with a view to better quality of life and greater survival
      among these individuals, even among those with genetic predisposition to rapid
      disease progression.

PMID- 15962070
TI  - [Social representations associated with tube feeding among adult hospitalized
      patients].
AB  - This study aimed to identify and understand adult patients' representations on
      tube feeding. Data were collected through interviews with sixteen patients who
      were using feeding tubes, which were analyzed through discourse analysis and
      Social Representation Theory. We identified a sequence in which representations
      are reorganized and redefined through experience, in order to turn this treatment
      tolerable. This sequence begins when patients face the need of a feeding tube,
      followed by the experience of its use and finally, when deciding about continuing
      its use or not, when going home. Some representations contribute to treatment
      adherence and others to its rejection. Getting to know positive and negative
      ideas about this treatment makes it possible to approach these patients in a more
      direct way, with a view to better adherence and satisfaction.

PMID- 15962071
TI  - [The contribution of belly dance to body education, physical and mental health of
      women who go to the gym or dance].
AB  - This qualitative study aimed to examine the benefits of belly dance for the
      health of women who go to a gym in the interior of Sao Paulo state, Brazil and
      was based on the researchers' experience and other literature on dancing. The
      references were the experience of the researcher and other literature on the
      dance area. The sample consisted of 12 women from 16 to 40 years of age who
      practiced belly dance for more than three months, who received a questionnaire
      with open questions. The analysis of their answers demonstrated that belly dance
      is beneficial for an integral education that values life, improving these women's
      health and quality of life.

PMID- 15962072
TI  - [The therapist in group psychotherapy].
AB  - Nowadays, group psychotherapy designates a broad range of procedures based on
      different theoretical frameworks, applied to several contexts. The purpose of
      this study is to understand the group therapist's role, delineating some
      strategies and necessary abilities for group psychotherapy practice. The authors
      emphasize the technical-scientific level in which the work with groups is
      developed and the influence of the therapist's personality on the participants.
      They conclude that, in order to preserve their role without loosing the
      specificity of his function due to his involvement in multiple patients'
      experiences, therapists must have a stable professional identity. Therefore, the
      therapists' preparation, based on a process of continuing formation, is a
      necessary condition to enable them to face peculiar situations that occur in the
      group context and also to assure the singular therapeutic potential of group
      psychotherapy.

PMID- 15962073
TI  - [Reflections on stress and burnout and their relationship with nursing].
AB  - This bibliographic review aimed to differentiate between stress and Burnout and
      to establish their relationship with nursing work to support the understanding of
      psychical suffering at work. The study was based on the analysis and
      interpretation of articles, thesis and dissertations produced between 1990 and
      2001. Although there is a consensus among the individuals on the existence of
      stress and burnout, there are several controversies surrounding these terms.
      These theories were created in the context of capitalist production increase.
      Stress refers to a personal tiring that interferes in the life of the person but
      not necessarily in his/her relationship with the work. Burnout is a syndrome
      involving negative attitudes and behaviors towards users, clients, organization
      and work. It is a gradual process of subjective experiences that result in
      practical and emotional problems to workers and organizations. Nursing work
      facilitates stress and burnout and causes suffering and illness among workers.

PMID- 15962074
TI  - [Team work in a family health care program: the team process concept and
      operational teams].
AB  - This work is a theoretical revision of team work in a family Health Care Program.
      We define team work in the health care field as a relationship network among
      people, power, knowledge, affection, and wishes, when there is a possibility of
      identifying group processes. We deal with concepts of Operational Group from the
      Argentinean School, which might help health professionals to get training in team
      work. We have visible (spoken) and invisible (unspoken) tasks within teams, which
      are modified and need to be combined and known. Communication, learning, the
      feeling of belonging, the atmosphere, the actions' pertinence for the team's
      purpose and power relations may help the team to get to know and analyze each
      other and to build a team. External supervision may help the team to turn itself
      into an operational team, working towards a life care project.

PMID- 15962075
TI  - [Academic activity report as a strategy for learning research].
AB  - This study aimed to analyze academic activity reports about the structure and
      mental abilities developed by graduate students of two nursing curriculum
      proposals at a Brazilian university. The study was based on 83 students: 39 from
      the Transition Curriculum (group I) and 44 from the Integrated Curriculum (group
      II). Data were collected through a registration card with topics from the
      December 2002 report by group I and the December 2003 report by group II. The
      results, presented as frequency percentages, showed that group II elaborated the
      academic activity report with a better structure than group I. This group also
      developed a more complex reasoning, especially in the "development" topic.
      Interventions with group II present a better development in this teaching
      strategy.

PMID- 15962076
TI  - [Situation of endemic pemphigus foliaceus in Mato Grosso do Sul, Brazil, 1990
      1999].
AB  - 307 cases were examined to characterize epidemiological aspects of endemic
      pemphigus foliaceus. The disease was predominantly identified in rural workers
      between 10 and 42 years old. Incidence was higher in the December, January,
      February, March and May (average: 30.7 cases/year). Our findings identified a
      corridor, coinciding with the state watershed.

PMID- 15962078
TI  - Correlation of nutritional status and food intake in hemodialysis patients.
AB  - BACKGROUND: Patients in end-stage renal disease often suffer from poor appetite,
      various comorbidities, and dietary restrictions. Despite regular hemodialysis,
      nutritional imbalances are frequently reported. Aiming to correlate nutritional
      status with food ingestion, a prospective study was done in an outpatient group.
      METHODS: Stable patients undergoing chronic hemodialysis for at least 3 months
      (n=44) were investigated by dietary recall and standard anthropometric,
      biochemical, and bioimpedance determinations, including subjective and objective
      global assessment. The mean age of the group was 47.0+/-16.9 years, and 63.6%
      were men. Body mass index was 22.2+/-3.9 kg/m2 (mean+/-SD), calorie intake was
      1471+/-601 kcal/day (20.7+/-6.7 kcal/kg/day), and protein ingestion was 74.3+/
      16.6 g protein/day (1.2 g/kg/day). Dietary and clinical findings were correlated
      with nutritional indices by linear regression analysis. RESULTS: Malnutrition
      estimated by subjective global assessment was very common (>90%), despite the
      fact that body mass index and serum albumin were within an acceptable range in
      the majority of the population. Objective global assessment yielded roughly
      comparable numerical findings, with 6.8% being well nourished, 61.4% at
      nutritional risk or lightly undernourished, 29.6% moderately malnourished, and
      2.3% severely malnourished. Total calorie intake was devoid of associations, but
      protein, carbohydrate, and lipid input positively correlated with triceps
      skinfold (P=.02). Lipid ingestion was the only marker directly associated with
      arm circumference, and it correlated with body mass index, as well as with total
      body fat (bioimpedance analysis) (P<.001). CONCLUSIONS: 1) Bioimpedance analysis
      was useful and was correlated with clinical findings; 2) Lipid intake was the
      best dietary index in this experience, surpassing protein or total energy; 3)
      Despite its shortcomings, dietary recall was useful in the assessment of
      hemodialysis patients.

PMID- 15962079
TI  - Endovascular treatment for intermittent claudication in patients who do not
      improve with clinical treatment.
AB  - PURPOSE: To study the results including long-term follow-up obtained with
      endovascular treatment of patients with intermittent claudication who did not
      experience clinical improvement with conservative treatment. METHODS: From
      January 1992 to January 2002, 62 of 1380 patients (4.5%) with intermittent
      claudication underwent endovascular treatment and were followed up for up to 120
      months (mean 76 months). The variables analyzed were the functioning of the
      arterial segment undergoing the endovascular procedure, the evolution of the
      maximum walking distance, and incidence of related morbidity and mortality.
      RESULTS: Fifty-two patients (84%) experienced no walking limitation after the
      procedure, and 6 patients (10%) improved but still exhibited some degree of
      limitation, for a total improved outcome of 94%. The patency rate was 82%. There
      was no intraoperative mortality. One primary failure and one immediate thrombosis
      occurred, and both were surgically corrected. Thrombosis of the treated artery
      occurred in 6 patients 12, 16, 25, 29, 62, and 66 months after the procedure.
      These patients started to experience intermittent claudication with a walking
      distance to onset that was similar to their presurgical distance to onset. During
      follow-up, a mortality rate of 12.9% (8 patients) was observed, 6 due to
      myocardial infarctions and 2 due cerebral infarction. Three patients underwent
      coronary bypasses 22, 36, and 55 months after the endovascular surgery, and 2
      patients underwent coronary angioplasty after 6 and 26 months. The mean follow up
      period was 76 months (range 0-120 months). CONCLUSION: This study shows that
      endovascular treatment of intermittent claudication brought about a lasting
      regression of the ischemic conditions in a significant number of patients, with
      excellent patency rates. It was concluded that this is a good alternative for
      selected patients, with low rates of complications and positive long-term
      results.

PMID- 15962080
TI  - Edema and malignancy in meningiomas.
AB  - PURPOSE: In recent years there have been many attempts to define a subset of
      aggressive malignant meningiomas based on histopathology and imaging
      technologies. The purpose of this study was to evaluate the level of peritumoral
      edema and its volume using the imaging technologies, computer tomography and
      magnetic resonance imaging, and correlate these results with the histological WHO
      classification. Reported causes of tumoral edema and its relationships to the
      histological characteristics were also reviewed. METHODS: The cases of 55
      patients with meningiomas who underwent surgery at the Hospital das Clinicas (Fac
      Med Univ Sao Paulo) between September 1993 and September 1997 were reviewed. The
      level of edema according to the classification of Ide et al. (1995) was compared
      to the histological WHO classification. RESULTS: Classification of the degree of
      edema was: level 0 edema--28 cases ; level I edema--19 cases; level II edema--8
      cases. Histological classification was: benign meningioma--43 cases; atypical
      meningiomas--11 cases; malignant meningioma--1 case. There was a significant
      (P=.0089) correlation between the degree of tumoral edema and the histological
      characteristics. CONCLUSIONS: These results suggest that the degree of edema as
      revealed by computer tomography and magnetic resonance imaging can be an
      important clinical predictive factor for the histological grade of the
      meningioma.

PMID- 15962081
TI  - Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA
      levels, and anthropometric parameters of their neonates.
AB  - PURPOSE: To study the effect of antiretroviral drugs administered during
      pregnancy on CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women and on
      the anthropometric parameters of their neonates. METHODS: A prospective study was
      conducted on 57 pregnant women and their neonates divided into 3 groups: ZDV
      Group, HIV-infected mothers taking zidovudine (n=20); triple therapy (TT) Group,
      mothers taking zidovudine+lamivudine+nelfinavir (n=25), and Control Group, normal
      women (n=12). CD4 lymphocyte counts and HIV-1 RNA levels of pregnant women were
      analyzed during two periods of pregnancy. The perinatal prognosis took into
      account preterm rates, birth weight, intrauterine growth restriction, perinatal
      death, and vertical transmission of HIV-1. Data were analyzed statistically using
      the nonparametric chi-square, Mann-Whitney, Friedman, Kruskal-Wallis, and
      Wilcoxon matched pairs tests, with the level of significance set at P<.05.
      RESULTS: The major maternal demographic and anthropometric data were homogeneous
      for the various groups. HIV-1 viral burden, which was initially elevated, median
      of 14,370 copies/mL, was significantly reduced in the TT group, reaching 40
      copies/mL. With respect to T-CD4+ lymphocyte counts, there was a significant
      recovery in Group TT at the end of pregnancy, this value being significantly
      different from that for the ZDV group (P=0052). There was no difference between
      groups regarding gestation length, Apgar scores, or neonatal anthropometric
      classification. There was no case of vertical HIV-1 transmission. CONCLUSIONS:
      The results obtained for the present series demonstrate the efficiency and
      suggest safety of the use of antiretroviral drugs during pregnancy as revealed by
      anthropometric parameters of the neonate.

PMID- 15962082
TI  - Study of warm ischemia followed by reperfusion on a lower limb model in rats:
      effect of allopurinol and streptokinase.
AB  - Prolonged tissue ischemia leads to changes in microcirculation and production of
      oxygen free radicals. The event eventually responsible for tissue death is the no
      reflow phenomenon and its management is a challenge for the surgeon dealing with
      replantation or transplantation. We introduce a model of warm ischemia and
      reperfusion of the lower limb of rats with which we studied the effect of
      allopurinol and streptokinase. METHOD: Section of the lower limb with
      preservation of vessels and nerves was performed in 110 rats. Femoral vessels
      clamped for periods of 0, 2, 4, 6, and 8 hours of ischemia were allowed to
      reperfuse (groups M0, M2, M4, M6, and M8 respectively). Other groups, E1, E2, and
      E3, received streptokinase, allopurinol, or a combination of the two drugs after
      6 hours of ischemia. RESULTS: Viability rates of the ischemic limbs after 7 days
      were 100% (M0), 80% (M2), 63.6% (M4), 50% (M6), and 20% (M8). In the experimental
      groups, E1, E2, and E3, viability rates were 67% (E1), 70% (E2), and 70% (E3).
      Groups M0, M2, M4, M6, and M8 differed among themselves except for groups M4 and
      M6. Group E1 had a higher rate of limb viability than M6 (control group) but not
      than M4. Groups E1, E2 and E3 had higher rates of limb viability than M6 but not
      than M2 or M4. DISCUSSION: The results suggest that increased viability of limbs
      after 6 hours of ischemia occurs when allopurinol or streptokinase is used. The
      combination of the two drugs does not appear to produce any additional effect.

PMID- 15962083
TI  - The level of nicotine dependence is an independent risk factor for cancer: a case
      control study.
AB  - BACKGROUND: Less than 20% of lifetime smokers will ever develop cancer. Smoking
      habits characteristics, particularly the level of nicotine dependence level, were
      not fully evaluated as a marker of risk. METHODS: Case-control study of voluntary
      patients prospectively enrolled in a smoking cessation program in a cancer
      hospital. For each cancer case, patients of the same age and sex were selected.
      The Beck Depression Inventory, an instrument for the diagnosis of depressive mood
      and clinical depression, and the Fagerstrom Test Questionnaire, a questionnaire
      that has a good correlation with nicotine levels, used to determine the degree of
      dependence on nicotine, were applied. Age on admission to the study, sex, and
      number of pack-years were also evaluated. RESULTS: From May 1999 to May 2002, 56
      cancer patients (case) and 85 matching controls (control) were identified in the
      population studied. There was no difference regarding pack-years. Fagerstrom Test
      Questionnaire was significantly higher in patients with cancer (7.5+/-1.9)
      compared to controls (6.3+/-2.0). We found a Fagerstrom Test Questionnaire>7 in
      73.2% of the cancer cases versus 43.5% of the controls (p=0.001). The proportion
      of depressed patients was higher in the cancer group (37.5% x 17.6%). Logistic
      regression adjusted for age and tobacco consumption disclosed that Fagerstrom
      Test Questionnaire score>7 has an odds ratio for cancer of 3.45 (95% CI 1.52
      7.83, p=0.003). CONCLUSION: Fagerstrom Test Questionnaire higher than 7 was
      identified as a risk factor for cancer in smokers with similar tobacco
      consumption.

PMID- 15962084
TI  - Coronary revascularization with the left internal thoracic artery and radial
      artery: comparison of short-term clinical evolution between elective and
      emergency surgery.
AB  - BACKGROUND: Left internal thoracic artery-to left anterior descending artery
      grafting has become a fundamental part of coronary artery bypass grafting. This
      grafting has led to increased use of other arterial conduits, of which the radial
      artery is most popular. Whether radial grafting can be used in the emergency
      patient is not known. This study compares the short-term clinical evolution
      between elective vs emergency coronary artery bypass grafting surgery with left
      internal thoracic artery and radial artery. METHODS: A retrospective study of 47
      patients who underwent elective or emergency coronary artery bypass grafting from
      1996 to 2003. All patients had coronary stenosis>70% in all target vessels. Only
      the left internal thoracic artery and radial artery were used as grafts. Patients
      were divided into elective group (23 patients) and emergency group (24 patients).
      Emergency criteria were unstable angina and/or critical coronary stenosis with
      high risk for acute myocardial infarction. Groups were similar for age and number
      of diseased vessels. RESULTS: The mean number of left internal thoracic artery
      grafts per patient in the elective and emergency groups were respectively 1.17
      and 1.38 (P=.17). The mean number of radial artery grafts per patient in the
      elective and emergency groups was respectively 2.26 and 2.08 (P=.48). The 30-day
      mortality was 0. There was no postoperative cardiogenic shock. The elective group
      had 1 acute myocardial infarction (4.4%) postoperatively, and emergency group had
      5 (20.8%). A nonsignificant trend towards acute myocardial infarction was noted
      in the emergency group (P=.18). Intensive care unit and postoperative stay were
      similar in both groups. CONCLUSION: Coronary artery bypass grafting using left
      internal thoracic artery and radial artery accomplishing complete
      revascularization can be performed in emergency patients with results similar to
      those for elective patients.

PMID- 15962085
TI  - Angiogenesis as an indicator of metastatic potential in papillary thyroid
      carcinoma.
AB  - Angiogenesis is new blood vessel formation, a process that can lead to tumor
      development. Microvessel count has been correlated to metastasis in some
      neoplasias. PURPOSE: To determine if measurement of microvessel density is useful
      in predicting metastasis to the cervical lymph node and prognosis in patients
      with papillary thyroid carcinoma. METHODS: A retrospective analysis was performed
      in 30 patients that had undergone total thyroidectomy. They were divided in 2
      groups of 15 patients--with and without metastatic disease. Immunohistochemistry
      was used to detect expression of CD34 in archival paraffin-embedded papillary
      thyroid tumors, and microvessel density was calculated based on it. Association
      between microvessel density and the presence of metastasis, according to
      histological subtype, disease recurrence, and AMES prognostic index groups was
      determined through statistical analysis. RESULTS: The median microvessel density
      for the patient group without metastasis (200.0 microvessels/mm2) was apparently,
      but not significantly, less than that observed among metastatic disease patients
      (254.4 microvessels/mm2) (P=.20). When papillary carcinoma subtypes were
      analyzed, this difference became significant (P=02). The follicular variant
      exhibited a greater microvessel density than the other subtypes, independent of
      metastasis presence. There was an apparent, but not significant, tendency for a
      larger median microvessel density in the group of patients that presented
      recurrence (294.4 microvessels/mm2 vs 249.6 microvessels/mm2, P=.11). There was
      no relationship between risk level and microvessel density: in the low- and high
      risk groups, the median MVD was 304.0 microvessels/mm2 and 229.6
      microvessels/mm2, respectively (P=.27). CONCLUSIONS: The results suggest that
      angiogenesis is more intense among metastatic tumors in the classic and the tall
      cell variants, indicating that microvessel count can be an indicator of the
      potential for metastasis in these subtypes of papillary thyroid carcinoma.
      Patients that developed recurrent disease had a tendency to exhibit higher
      angiogenesis; however, there was no association between microvessel density and
      the AMES prognostic index.

PMID- 15962086
TI  - Hypertension and depression.
AB  - Despite the high prevalence of depression and hypertension, the relationship
      between the two diseases has received little attention. This paper reviews the
      epidemiological, pathophysiological, and prognostic aspects of this association,
      as well as its implications for treatment. A Medline search was conducted using
      the following key words: depression, blood pressure, blood pressure variability,
      physical morbidity, hypertension, mood, stress, hypertension, antidepressive
      agents, and genetics, from 1980 to 2004. We found descriptions of increased
      prevalence of hypertension in depressed patients, increased prevalence of
      depression in hypertensive patients, association between depressive
      symptomatology and hypotension, and alteration of the circadian variation of
      blood pressure in depressed patients. There is considerable evidence suggesting
      that hyperreactivity of the sympathetic nervous system and genetic influences are
      the underlying mechanisms in the relationship between depression and
      hypertension. Depression can negatively affect the course of hypertensive
      illness. Additionally, the use of antidepressive agents can interfere with blood
      pressure control of patients with hypertension by inducing changes in blood
      pressure and orthostatic hypotension.

PMID- 15962087
TI  - Hereditary nonpolyposis colorectal cancer identification and surveillance of high
      risk families.
AB  - Hereditary nonpolyposis colorectal cancer is an autosomal dominant condition
      caused by highly penetrant gene mutations. It is characterized by increased
      susceptibility for a specific group of cancer, mainly colorectal cancer. The
      syndrome originates from the inheritance of mutations in DNA mismatch repair
      genes. The most commonly affected genes in hereditary nonpolyposis colorectal
      cancer are hMLH1 and hMSH2. Their deficient expression renders the cell
      susceptible to the accumulation of many molecular defects, a condition which can
      be evaluated by the instability in sections of base repeats in the genoma known
      as microsatellite instability. The molecular detection of hereditary nonpolyposis
      colorectal cancer is possible in most of the highly suspicious cases. Genetic
      tests for hereditary nonpolyposis colorectal cancer also allow characterization
      of the individual that bears the mutation within a family. The high cost and
      restricted availability of these tests hamper their use for every person
      presenting colorectal cancer. Due to this fact, some clinical criteria have been
      developed by a hereditary nonpolyposis colorectal cancer international
      organization to select families with a high probability of carrying the mutation.
      Once families at risk are identified, they are encouraged to join a screening
      program that aims at early detection of hereditary nonpolyposis colorectal cancer
      related cancers, increasing the possibility of its prevention and early
      detection.

PMID- 15962088
TI  - Antiphospholipid antibodies, thrombosis, and adenocarcinoma.

PMID- 15962089
TI  - Uremic stomatitis in chronic renal failure.

PMID- 15962090
TI  - Phantom limb pain induced by spinal anesthesia.

PMID- 15962091
TI  - Nitric oxide as a regulator of inflammatory processes.
AB  - Nitric oxide (NO) plays an important role in mediating many aspects of
      inflammatory responses. NO is an effector molecule of cellular injury, and can
      act as an anti-oxidant. It can modulate the release of various inflammatory
      mediators from a wide range of cells participating in inflammatory responses
      (e.g., leukocytes, macrophages, mast cells, endothelial cells, and platelets). It
      can modulate blood flow, adhesion of leukocytes to the vascular endothelium and
      the activity of numerous enzymes, all of which can have an impact on inflammatory
      responses. In recent years, NO-releasing drugs have been developed, usually as
      derivatives of other drugs, which exhibit very powerful anti-inflammatory
      effects.

PMID- 15962092
TI  - Nitric oxide: a major determinant of mast cell phenotype and function.
AB  - Mast cells (MC) are important in the numerous physiological processes of
      homeostasis and disease. Most notably, MC are critical effectors in the
      development and exacerbation of allergic disorders. Nitric oxide (NO) is a
      diatomic radical produced by nitric oxide synthase (NOS), and has pluripotent
      cell signaling and cytotoxic properties. NO can influence many MC functions.
      Recent evidence shows the source of this NO can be from the mast cell itself.
      Governing the production of this endogenous NO, through alterations in the
      expression of tetrahydrobiopterin (BH4), a NOS cofactor, has stabilizing effects
      on MC degranulation. Furthermore, NO regulates the synthesis and secretion of de
      novo generated mediators, including leukotrienes and chemokines. These novel
      observations add to the growing body of knowledge surrounding the role of NO in
      the MC.

PMID- 15962093
TI  - Regulation of endothelial derived nitric oxide in health and disease.
AB  - Endothelial nitric oxide synthase (eNOS) is the primary physiological source of
      nitric oxide (NO) that regulates cardiovascular homeostasis. Historically eNOS
      has been thought to be a constitutively expressed enzyme regulated by calcium and
      calmodulin. However, in the last five years it is clear that eNOS activity and NO
      release can be regulated by post-translational control mechanisms (fatty acid
      modification and phosphorylation) and protein-protein interactions (with caveolin
      1 and heat shock protein 90) that direct impinge upon the duration and magnitude
      of NO release. This review will summarize this information and apply the post
      translational control mechanisms to disease states.

PMID- 15962094
TI  - Nitric oxide paradox in asthma.
AB  - Asthma results from allergen-driven intrapulmonary Th2 response, and is
      characterized by intermittent airway obstruction, airway hyperreactivity (AHR),
      and airway inflammation. Accumulating evidence indicates that inflammatory
      diseases of the respiratory tract are commonly associated with elevated
      production of nitric oxide (NO). It has been shown that exhaled NO may be derived
      from constitutive NO synthase (NOS) such as endothelial (NOS 3) and neural (NOS
      1) in normal airways, while increased levels of NO in asthma appear to be derived
      from inducible NOS2 expressed in the inflamed airways. Nevertheless, the
      functional role of NO and NOS isoforms in the regulation of AHR and airway
      inflammation in human or experimental models of asthma is still highly
      controversial. In the present commentary we will discuss the role of
      lipopolysaccharides contamination of allergens as key element in the controversy
      related to the regulation of NOS2 activity in experimental asthma.

PMID- 15962095
TI  - Nitric oxide synthase activity and endogenous inhibitors in rats recovered from
      allergic encephalomyelitis.
AB  - We have previously reported that in comparison with normal rats, the presence of
      experimental allergic encephalomyelitis (EAE) leads to decreased endogenous
      inhibitory activity (EIA) of Ca2+-dependent nitric oxide synthase (NOS) in both
      brain and serum, and increased expression of protein 3-nitrotyrosine (NT) in
      brain. In this work we show that animals recovered from the clinical signs of EAE
      are not different from controls in terms of either brain NOS activity, EIA of
      NOS, or NT expression. These results suggest that parallel to the reversal of the
      disease symptoms, a normalization of the production of nitric oxide and related
      species occurs.

PMID- 15962096
TI  - The pathogenesis of diabetic complications: the role of DNA injury and poly(ADP
      ribose) polymerase activation in peroxynitrite-mediated cytotoxicity.
AB  - Recent work has demonstrated that hyperglycemia-induced overproduction of
      superoxide by the mitochondrial electron-transport chain triggers several
      pathways of injury [(protein kinase C (PKC), hexosamine and polyol pathway
      fluxes, advanced glycation end product formation (AGE)] involved in the
      pathogenesis of diabetic complications by inhibiting glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) activity. Increased oxidative and nitrosative stress
      activates the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP). PARP
      activation, on one hand, depletes its substrate, NAD+, slowing the rate of
      glycolysis, electron transport and ATP formation. On the other hand, PARP
      activation results in inhibition of GAPDH by poly-ADP-ribosylation. These
      processes result in acute endothelial dysfunction in diabetic blood vessels,
      which importantly contributes to the development of various diabetic
      complications. Accordingly, hyperglycemia-induced activation of PKC and AGE
      formation are prevented by inhibition of PARP activity. Furthermore, inhibition
      of PARP protects against diabetic cardiovascular dysfunction in rodent models of
      cardiomyopathy, nephropathy, neuropathy, and retinopathy. PARP activation is also
      present in microvasculature of human diabetic subjects. The present review
      focuses on the role of PARP in diabetic complications and emphasizes the
      therapeutic potential of PARP inhibition in the prevention or reversal of
      diabetic complications.

PMID- 15962097
TI  - An overview of the effects of annexin 1 on cells involved in the inflammatory
      process.
AB  - The concept of anti-inflammation is currently evolving with the definition of
      several endogenous inhibitory circuits that are important in the control of the
      host inflammatory response. Here we focus on one of these pathways, the annexin 1
      (ANXA1) system. Originally identified as a 37 kDa glucocorticoid-inducible
      protein, ANXA1 has emerged over the last decade as an important endogenous
      modulator of inflammation. We review the pharmacological effects of ANXA1 on cell
      types involved in inflammation, from blood-borne leukocytes to resident cells.
      This review reveals that there is scope for more research, since most of the
      studies have so far focused on the effects of the protein and its peptido
      mimetics on neutrophil recruitment and activation. However, many other cells
      central to inflammation, e.g. endothelial cells or mast cells, also express
      ANXA1: it is foreseen that a better definition of the role(s) of the endogenous
      protein in these cells will open the way to further pharmacological studies. We
      propose that a more systematic analysis of ANXA1 physio-pharmacology in cells
      involved in the host inflammatory reaction could aid in the design of novel anti
      inflammatory therapeutics based on this endogenous mediator.

PMID- 15962098
TI  - New insights into the anti-inflammatory actions of aspirin-induction of nitric
      oxide through the generation of epi-lipoxins.
AB  - Aspirin has always remained an enigmatic drug. Not only does it present with new
      benefits for treating an ever-expanding list of apparently unrelated diseases at
      an astounding rate but also because aspirin enhances our understanding of the
      nature of these diseases process. Originally, the beneficial effects of aspirin
      were shown to stem from its inhibition of cyclooxygenase-derived prostaglandins,
      fatty acid metabolites that modulate host defense. However, in addition to
      inhibiting cyclooxygenase activity aspirin can also inhibit pro-inflammatory
      signaling pathways, gene expression and other factors distinct from eicosanoid
      biosynthesis that drive inflammation as well as enhance the synthesis of
      endogenous protective anti-inflammatory factors. Its true mechanism of action in
      anti-inflammation remains unclear. Here the data from a series of recent
      experiments proposing that one of aspirin's predominant roles in inflammation is
      the induction of nitric oxide, which potently inhibits leukocyte/endothelium
      interaction during acute inflammation, will be discussed. It will be argued that
      this nitric oxide-inducing effects are exclusive to aspirin due to its unique
      ability, among the family of traditional anti-inflammatory drugs, to acetylate
      the active site of inducible cyclooxygenase and generate a family of lipid
      mediators called the epi-lipoxins that are increasingly being shown to have
      profound roles in a range of host defense responses.

PMID- 15962099
TI  - Lipoxin agonists: turn right! to path of resolving neutrophil.
AB  - An impressive array of cellular and molecular adaptive responses achieves
      homeostasis. The inflammatory reaction is an adaptive response triggered by an
      insult to culminate into the overt cardinal signs of inflammation, eventually
      leading to resolution and returning the organism back to its original centered
      state. This article focuses on some aspects of the lipoxin A4 signaling pathway
      during the resolution phase, to better understand molecular mechanisms by which a
      neutrophil directs an inflammatory reaction to switch off and resume homeostasis.
      Defining the resolution state of a neutrophil at the molecular level will aid in
      treatments of diseases that are associated with an exaggerated and uncontrolled
      inflammation.

PMID- 15962100
TI  - The balance between the production of tumor necrosis factor-alpha and interleukin
      10 determines tissue injury and lethality during intestinal ischemia and
      reperfusion.
AB  - A major goal in the treatment of acute ischemia of a vascular territory is to
      restore blood flow to normal values, i.e. to "reperfuse" the ischemic vascular
      bed. However, reperfusion of ischemic tissues is associated with local and
      systemic leukocyte activation and trafficking, endothelial barrier dysfunction in
      postcapillary venules, enhanced production of inflammatory mediators and great
      lethality. This phenomenon has been referred to as "reperfusion injury" and
      several studies demonstrated that injury is dependent on neutrophil recruitment.
      Furthermore, ischemia and reperfusion injury is associated with the coordinated
      activation of a series of cytokines and adhesion molecules. Among the mediators
      of the inflammatory cascade released, TNF-alpha appears to play an essential role
      for the reperfusion-associated injury. On the other hand, the release of IL-10
      modulates pro-inflammatory cytokine production and reperfusion-associated tissue
      injury. IL-1beta, PAF and bradykinin are mediators involved in ischemia and
      reperfusion injury by regulating the balance between TNF-alpha and IL-10
      production. Strategies that enhance IL-10 and/or prevent TNF-alpha concentration
      may be useful as therapeutic adjuvants in the treatment of the tissue injury that
      follows ischemia and reperfusion.

PMID- 15962101
TI  - Nitric oxide and the resolution of inflammation: implications for
      atherosclerosis.
AB  - The ubiquitous free radical, nitric oxide (NO), plays an important role in many
      biological processes including the regulation of the inflammatory response.
      Alterations in NO synthesis by endogenous systems likely influence inflammatory
      processes occurring in a wide range of diseases including many in the
      cardiovascular system (e.g. atherosclerosis). Progression of inflammatory
      conditions depends not only upon the recruitment and activation of inflammatory
      cells but also upon their subsequent removal from the inflammatory milieu.
      Apoptosis, or programmed cell death, is a fundamental process regulating
      inflammatory cell survival and is critically involved in ensuring the successful
      resolution of an inflammatory response. Apoptosis results in shutdown of
      secretory pathways and renders effete, but potentially highly histotoxic, cells
      instantly recognisable for non-inflammatory clearance by phagocytes (e.g.,
      macrophages). However, dysregulation of apoptosis and phagocytic clearance
      mechanisms can have drastic consequences for development and resolution of
      inflammatory processes. In this review we highlight the complexities of NO
      mediated regulation of inflammatory cell apoptosis and clearance by phagocytes
      and discuss the molecular mechanisms controlling these NO mediated effects. We
      believe that manipulation of pathways involving NO may have previously
      unrecognised therapeutic potential for limiting or resolving inflammatory and
      cardiovascular disease.

PMID- 15962103
TI  - Regulating inflammation through the anti-inflammatory enzyme platelet-activating
      factor-acetylhydrolase.
AB  - Platelet-activating factor (PAF) is one of the most potent lipid mediators
      involved in inflammatory events. The acetyl group at the sn-2 position of its
      glycerol backbone is essential for its biological activity. Deacetylation induces
      the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is
      catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2
      that also degrades a family of PAF-like oxidized phospholipids with short sn-2
      residues. Biochemical and enzymological evaluations revealed that at least three
      types of PAF-AH exist in mammals, namely the intracellular types I and II and a
      plasma type. Many observations indicate that plasma PAF AH terminates signals by
      PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In
      this review, we will focus on the potential of PAF-AH as a modulator of diseases
      of dysregulated inflammation.

PMID- 15962102
TI  - Mechanisms of eosinophil cytokine release.
AB  - Human eosinophils have been demonstrated to contain a multitude of cytokines and
      chemokines that exist pre-formed within these cells. This content of pre-formed
      cytokines, with diverse potential biologic activities, provides eosinophils with
      capabilities distinct from most other leukocytes. The localization of pre-formed
      cytokines within eosinophils is both within specific granules and associated with
      substantial numbers of morphologically distinct cytoplasmic vesicles. Stimulation
      for release of specific cytokines, such as IL-4, leads to a regulated signal
      transduction cascade, which is dependent on the formation of leukotriene C4
      within eosinophils where it acts as an intracrine mediator. IL-4 release occurs
      selectively and is by means of vesicular transport. The capabilities of
      eosinophils not only to rapidly release pre-formed cytokines but also to
      differentially regulate which cytokines are released endow eosinophils with
      distinct abilities in innate and acquired immunity.

PMID- 15962104
TI  - CC-chemokine receptors: a potential therapeutic target for Trypanosoma cruzi
      elicited myocarditis.
AB  - The comprehension of the pathogenesis of Trypanosoma cruzi-elicited myocarditis
      is crucial to delineate new therapeutic strategies aiming to ameliorate the
      inflammation that leads to heart dysfunction, without hampering parasite control.
      The augmented expression of CCL5/RANTES and CCL3/MIP-1alpha, and their receptor
      CCR5, in the heart of T. cruzi-infected mice suggests a role for CC-chemokines
      and their receptors in the pathogenesis of T. cruzi-elicited myocarditis. Herein,
      we discuss our recent results using a CC-chemokine receptor inhibitor (Met
      RANTES), showing the participation of CC-chemokines in T. cruzi infection and
      unraveling CC-chemokine receptors as an attractive therapeutic target for further
      evaluation in Chagas disease.

PMID- 15962105
TI  - Mechanisms for suppressing NADPH oxidase in the vascular wall.
AB  - Oxidative stress underlies many forms of vascular disease as well as tissue
      injury following ischemia and reperfusion. The major source of oxidative stress
      in the artery wall is an NADPH oxidase. This enzyme complex as expressed in
      vascular cells differs from that in phagocytic leucocytes both in biochemical
      structure and functions. The crucial flavin-containing catalytic subunits, Nox1
      and Nox4, are not found in leucocytes, but are highly expressed in vascular cells
      and upregulated with vascular remodeling, such as that found in hypertension and
      atherosclerosis. The difference in catalytic subunits offers the opportunity to
      develop "vascular specific" NADPH oxidase inhibitors that do not compromise the
      essential physiological signaling and phagocytic functions carried out by
      reactive oxygen and nitrogen species. Nitric oxide and targeted inhibitors of
      NADPH oxidase that block the source of oxidative stress in the vasculature are
      more likely to prevent the deterioration of vascular function that leads to
      stroke and heart attack, than are conventional antioxidants. The roles of Nox
      isoforms in other inflammatory conditions are yet to be explored.

PMID- 15962106
TI  - Hemopressin: a novel bioactive peptide derived from the alpha1-chain of
      hemoglobin.
AB  - Hemopressin (PVNFKFLSH), a novel bioactive peptide derived from the alpha1-chain
      of hemoglobin, was originally isolated from rat brain homogenates. Hemopressin
      causes hypotension in anesthetized rats and is metabolized in vivo and in vitro
      by endopeptidase 24.15 (EP24.15), neurolysin (EP24.16), and angiotensin
      converting enzyme (ACE). Hemopressin also exerts an antinociceptive action in
      experimental inflammatory hyperalgesia induced by carrageenin or bradykinin via a
      mechanism that is independent of opioids. These findings suggest that this
      peptide may have important regulatory physiological actions in vivo.

PMID- 15962107
TI  - Lymphatic vessel contractile activity and intestinal inflammation.
AB  - Edema is a consistent observation in inflammatory bowel disease (IBD), and immune
      responses are inevitable in inflammation. Because the lymphatic system is an
      integral part of both tissue fluid homeostasis and immune reactions, it is likely
      that lymphatics play a role in the complex etiology of IBD. Despite the
      consistent findings that the lymphatic system is altered during gastrointestinal
      inflammation, the majority of studies conducted on the disease only mention the
      lymphatic system in passing. The effects of inflammatory mediators on lymphatic
      vessel function also remain poorly defined, despite its essential role in
      immunity and prevention of tissue edema. Processes allowing effective lymph
      transport are altered during inflammation, however, the mode of alteration and
      reason why lymphatics are ineffective in inflammatory reactions need to be
      further investigated. In addition, these processes have not yet been examined in
      an appropriate animal model and little has been done using in vivo methods of
      investigation in any model of gastrointestinal inflammation. This paper reviews
      the role of the lymphatic system in intestinal inflammation, as well as the role
      of the inflammatory products in mediating lymphatic contractile function.

PMID- 15962108
TI  - P2X1 receptors and the endothelium.
AB  - Adenosine triphosphate (ATP) is now established as a principle vaso-active
      mediator in the vasculature. Its actions on arteries are complex, and are
      mediated by the P2X and P2Y receptor families. It is generally accepted that ATP
      induces a bi-phasic response in arteries, inducing contraction via the P2X and
      P2Y receptors on the smooth muscle cells, and vasodilation via the actions of P2Y
      receptors located on the endothelium. However, a number of recent studies have
      placed P2X1 receptors on the endothelium of some arteries. The use of a specific
      P2X1 receptor ligand, alpha, beta methylene ATP has demonstrated that P2X1
      receptors also have a bi-functional role. The actions of ATP on P2X1 receptors is
      therefore dependant on its location, inducing contraction when located on the
      smooth muscle cells, and dilation when expressed on the endothelium, comparable
      to that of P2Y receptors.

PMID- 15962109
TI  - Mechanisms of leukocyte lipid body formation and function in inflammation.
AB  - An area of increasingly interest for the understanding of cell signaling are the
      spatio-temporal aspects of the different enzymes involved in lipid mediator
      generation (eicosanoid-forming enzymes, phospholipases and their regulatory
      kinases and phosphatases) and pools of lipid precursors. The compartmentalization
      of signaling components within discrete and dynamic sites in the cell is critical
      for specificity and efficiency of enzymatic reactions of phosphorilation, enzyme
      activation and function. We hypothesized that lipid bodies--inducible non
      membrane bound cytoplasmic lipid domains--function as specialized intracellular
      sites of compartmentalization of signaling with major roles in lipid mediator
      formation within leukocytes engaged in inflammatory process. Over the past years
      substantial progresses have been made demonstrating that all enzymes involved in
      eicosanoid synthesis localize at lipid bodies and lipid bodies are distinct sites
      for eicosanoid generation. Here we will review our current knowledge on the
      mechanisms of formation and functions of lipid bodies pertinent to inflammation.

PMID- 15962110
TI  - Mast cell changes in experimental diabetes: focus on attenuation of allergic
      events.
AB  - The prevalence of atopic diseases and diabetes is increasing worldwide though the
      concurrence of these pathologies in individual patients is found less frequent
      than it would be predicted. Moreover, co-existence of diabetes and allergy is
      generally marked by attenuation of their respective symptoms, and effective
      treatment of one disease exacerbates the other. This review gives an update of
      the state-of-the-art concerning the intercurrence of allergy and diabetes,
      particularly focusing on the consequences to the allergen-evoked vascular and
      cellular changes. It is proposed that the reduction in mast cell numbers and
      reactivity may be a pivotal mechanism behind the mutual exclusion phenomenon.

PMID- 15962111
TI  - Thymus involution in alloxan diabetes: analysis of mast cells.
AB  - We previously reported that alloxan-induced diabetes results in reduction in the
      number and reactivity of mast cells at different body sites. In this study, the
      influence of diabetes on thymic mast cells was investigated. Thymuses from
      diabetic rats showed marked alterations including shrinkage, thymocyte depletion,
      and increase in the extracellular matrix network, as compared to those profiles
      seen in normal animals. Nevertheless, we noted that the number and reactivity of
      mast cells remained unchanged. These findings indicate that although diabetes
      leads to critical alterations in the thymus, the local mast cell population is
      refractory to its effect. This suggests that thymic mast cells are under a
      different regulation as compared to those located in other tissues.

PMID- 15962112
TI  - Selective PDE4 inhibitors as potent anti-inflammatory drugs for the treatment of
      airway diseases.
AB  - Phosphodiesterases (PDEs) are responsible for the breakdown of intracellular
      cyclic nucleotides, from which PDE4 are the major cyclic AMP metabolizing
      isoenzymes found in inflammatory and immune cells. This generated greatest
      interest on PDE4 as a potential target to treat lung inflammatory diseases. For
      example, cigarette smoke-induced neutrophilia in BAL was dose and time
      dependently reduced by cilomilast. Beside the undesired side effects associated
      with the first generation of PDE4 inhibitors, the second generation of selective
      inhibitors such as cilomilast and roflumilast showed clinical efficacy in asthma
      and chronic obstructive pulmonary diseases trials, thus re-enhancing the interest
      on these classes of compounds. However, the ability of PDE4 inhibitors to prevent
      or modulate the airway remodelling remains relatively unexplored. We demonstrated
      that selective PDE4 inhibitor RP 73-401 reduced matrix metalloproteinase (MMP)-9
      activity and TGF-beta1 release during LPS-induced lung injury in mice and that CI
      1044 inhibited the production of MMP-1 and MMP-2 from human lung fibroblasts
      stimulated by pro-inflammatory cytokines. Since inflammatory diseases of the
      bronchial airways are associated with destruction of normal tissue structure, our
      data suggest a therapeutic benefit for PDE4 inhibitors in tissue remodelling
      associated with chronic lung diseases.

PMID- 15962113
TI  - The role of interferon-gamma on immune and allergic responses.
AB  - Allergic diseases have been closely related to Th2 immune responses, which are
      characterized by high levels of interleukin (IL) IL-4, IL-5, IL-9 and IL-13.
      These cytokines orchestrate the recruitment and activation of different effector
      cells, such as eosinophils and mast cells. These cells along with Th2 cytokines
      are key players on the development of chronic allergic inflammatory disorders,
      usually characterized by airway hyperresponsiveness, reversible airway
      obstruction, and airway inflammation. Accumulating evidences have shown that
      altering cytokine-producing profile of Th2 cells by inducing Th1 responses may be
      protective against Th2-related diseases such as asthma and allergy. Interferon
      gamma (IFN-gamma), the principal Th1 effector cytokine, has shown to be crucial
      for the resolution of allergic-related immunopathologies. In fact, reduced
      production of this cytokine has been correlated with severe asthma. In this
      review, we will discuss the role of IFN-gamma during the generation of immune
      responses and its influence on allergic inflammation models, emphasizing its
      biologic properties during the different aspects of allergic responses.

PMID- 15962114
TI  - Regulation of stem cell factor expression in inflammation and asthma.
AB  - Stem cell factor (SCF) is a major mast cell growth factor, which could be
      involved in the local increase of mast cell number in the asthmatic airways. In
      vivo, SCF expression increases in asthmatic patients and this is reversed after
      treatment with glucocorticoids. In vitro in human lung fibroblasts in culture, IL
      1beta, a pro-inflammatory cytokine, confirms this increased SCF mRNA and protein
      expression implying the MAP kinases p38 and ERK1/2 very early post-treatment, and
      glucocorticoids confirm this decrease. Surprisingly, glucocorticoids potentiate
      the IL-1beta-enhanced SCF expression at short term treatment, implying increased
      SCF mRNA stability and SCF gene transcription rate. This potentiation involves
      p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1
      also confirm this increase and decrease of SCF expression by IL-1beta and
      glucocorticoids, and the potentiation by glucocorticoids of the IL-1beta-induced
      SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation,
      and the effect of IL-1beta or glucocorticoids alone. DNA binding of GR and NF
      kappaB are also demonstrated for these effects. In conclusion, this review
      concerns new mechanisms of regulation of SCF expression in inflammation that
      could lead to potential therapeutic strategy allowing to control mast cell number
      in the asthmatic airways.

PMID- 15962115
TI  - Selective suppression of leukocyte recruitment in allergic inflammation.
AB  - Allergic diseases result in a considerable socioeconomic burden. The incidence of
      allergic diseases, notably allergic asthma, has risen to high levels for reasons
      that are not entirely understood. With an increasing knowledge of underlying
      mechanisms, there is now more potential to target the inflammatory process rather
      than the overt symptoms. This focuses attention on the role of leukocytes
      especially Th2 lymphocytes that regulate allergic inflammation and effector cells
      where eosinophils have received much attention. Eosinophils are thought to be
      important based on the high numbers that are recruited to sites of allergic
      inflammation and the potential of these cells to effect both tissue injury and
      remodelling. It is hoped that future therapy will be directed towards specific
      leukocyte types, without overtly compromising essential host defence responses.
      One obvious target is leukocyte recruitment. This necessitates a detailed
      understanding of underlying mechanisms, particularly those involving soluble
      chemoattractants signals and cell-cell adhesion molecules.

PMID- 15962116
TI  - Local anaesthetic medication for the treatment of asthma.
AB  - It is presumed that drugs able to prevent bronchial spasm and/or inflammation may
      have therapeutic potential to control asthma symptoms. The local anaesthetic
      lidocaine has recently received increased attention as an alternative form of
      treatment for asthmatic patients. This paper reviews the major findings on the
      topic and summarizes the putative mechanisms underlying the airway effects of
      local anaesthetic agents. We think that lidocaine extends the spectrum of options
      in asthma therapy, probably by counteracting both spasmogenic and inflammatory
      stimuli in the bronchial airways. The possibility of development of new anti
      asthma compounds based on the synthesis of lidocaine derivatives is also on the
      horizon.

PMID- 15962117
TI  - Macrophage elastase (MMP-12): a pro-inflammatory mediator?
AB  - As many metalloproteinases (MMPs), macrophage elastase (MMP-12) is able to
      degrade extracellular matrix components such as elastin and is involved in tissue
      remodeling processes. Studies using animal models of acute and chronic pulmonary
      inflammatory diseases, such as pulmonary fibrosis and chronic obstructive
      pulmonary disease (COPD), have given evidences that MMP-12 is an important
      mediator of the pathogenesis of these diseases. However, as very few data
      regarding the direct involvement of MMP-12 in inflammatory process in the airways
      were available, we have instilled a recombinant form of human MMP-12 (rhMMP-12)
      in mouse airways. Hence, we have demonstrated that this instillation induced a
      severe inflammatory cell recruitment characterized by an early accumulation of
      neutrophils correlated with an increase in proinflammatory cytokines and in
      gelatinases and then by a relatively stable recruitment of macrophages in the
      lungs over a period of ten days. Another recent study suggests that resident
      alveolar macrophages and recruited neutrophils are not involved in the delayed
      macrophage recruitment. However, epithelial cells could be one of the main
      targets of rhMMP-12 in our model. We have also reported that a corticoid,
      dexamethasone, phosphodiesterase 4 inhibitor, rolipram and a non-selective MMP
      inhibitor, marimastat could reverse some of these inflammatory events. These data
      indicate that our rhMMP-12 model could mimic some of the inflammatory features
      observed in COPD patients and could be used for the pharmacological evaluation of
      new anti-inflammatory treatment. In this review, data demonstrating the
      involvement of MMP-12 in the pathogenesis of pulmonary fibrosis and COPD as well
      as our data showing a pro-inflammatory role for MMP-12 in mouse airways will be
      summarized.

PMID- 15962118
TI  - Protease-activated receptors and inflammatory hyperalgesia.
AB  - Recent advances in basic science pointed to a role for proteinases, through the
      activation of proteinase-activated receptors (PARs) in nociceptive mechanisms.
      Activation of PAR1, PAR2 and PAR4 either by proteinases or by selective agonists
      causes inflammation inducing most of the cardinal signs of inflammation:
      swelling, redness, and pain. Sub-inflammatory doses of PAR2 agonist still induced
      hyperalgesia and allodynia while PAR2 has been shown to be implicated in the
      generation of hyperalgesia in different inflammatory models. In contrast, sub
      inflammatory doses of PAR1 increases nociceptive threshold, inhibiting
      inflammatory hyperalgesia, thereby acting as an analgesic agent. PARs are present
      and functional on sensory neurons, where they participate either directly or
      indirectly to the transmission and/or inhibition of nociceptive messages. Taken
      together, the results discussed in this review highlight proteinases as signaling
      molecules to sensory nerves. We need to consider proteinases and the receptors
      that are activated by proteinases as important potential targets for the
      development of analgesic drugs in the treatment of inflammatory pain.

PMID- 15962119
TI  - Role of protease-activated receptor-2 in inflammation, and its possible
      implications as a putative mediator of periodontitis.
AB  - Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein
      coupled receptors with seven-transmembrane domains. This receptor is widely
      distributed throughout the body and seems to be importantly involved in
      inflammatory processes. PAR2 can be activated by serine proteases such as
      trypsin, mast cell tryptase, and bacterial proteases, such as gingipain produced
      by Porphyromonas gingivalis. This review describes the current stage of knowledge
      of the possible mechanisms that link PAR2 activation with periodontal disease,
      and proposes future therapeutic strategies to modulate the host response in the
      treatment of periodontitis.

PMID- 15962120
TI  - Inflammatory effects of snake venom metalloproteinases.
AB  - Metalloproteinases are abundant enzymes in crotaline and viperine snake venoms.
      They are relevant in the pathophysiology of envenomation, being responsible for
      local and systemic hemorrhage frequently observed in the victims. Snake venom
      metalloproteinases (SVMP) are zinc-dependent enzymes of varying molecular weights
      having multidomain organization. Some SVMP comprise only the proteinase domain,
      whereas others also contain a disintegrin-like domain, cysteine-rich, and lectin
      domains. They have strong structural similarities with both mammalian matrix
      metalloproteinases (MMP) and members of ADAMs (a disintegrin and
      metalloproteinase) group. Besides hemorrhage, snake venom metalloproteinase
      induce local myonecrosis, skin damage, and inflammatory reaction in experimental
      models. Local inflammation is an important characteristic of snakebite
      envenomations inflicted by viperine and crotaline snake species. Thus, in the
      recent years there is a growing effort to understand the mechanisms responsible
      for SVMP-induced inflammatory reaction and the structural determinants of this
      effect. This short review focuses the inflammatory effects evoked by SVMP.

PMID- 15962121
TI  - Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial
      injury and malfunction.
AB  - T lymphocyte-mediated pathogenesis is common to a variety of enteropathies,
      including giardiasis, cryptosporidiosis, bacterial enteritis, celiac's disease,
      food anaphylaxis, and Crohn's disease. In giardiasis as well as in these other
      disorders, a diffuse loss of microvillous brush border, combined or not with
      villus atrophy, is responsible for disaccharidase insufficiencies and
      malabsorption of electrolytes, nutrients, and water, which ultimately cause
      diarrheal symptoms. Other mucosal changes may include crypt hyperplasia and
      increased infiltration of intra-epithelial lymphocytes. Recent studies using
      models of giardiasis have shed new light on the immune regulation of these
      abnormalities. Indeed, experiments using an athymic mouse model of infection have
      found that these epithelial injuries were T cell-dependent. Findings from further
      research indicate that that the loss of brush border surface area, reduced
      disaccharidase activities, and increase crypt-villus ratios are mediated by CD8+
      T cells, whereas both CD8+ and CD4+ small mesenteric lymph node T cells regulate
      the influx of intra-epithelial lymphocytes. Future investigations need to
      characterize the CD8+ T cell signaling cascades that ultimately lead to
      epithelial injury and malfunction in giardiasis and other malabsorptive disorders
      of the intestine.

PMID- 15962122
TI  - Neutrophil transepithelial migration: role of toll-like receptors in mucosal
      inflammation.
AB  - The symptomatic phases of many inflammatory diseases are characterized by
      migration of large numbers of neutrophils (PMN) across a polarized epithelium and
      accumulation within a lumen. For example, acute PMN influx is common in diseases
      of the gastrointestinal system (ulcerative colitis, Crohn's disease, bacterial
      enterocolitis, gastritis), hepatobiliary system (cholangitis, acute
      cholecystitis), respiratory tract (bronchial pneumonia, bronchitis, cystic
      fibrosis, bronchiectasis), and urinary tract (pyelonephritis, cystitis). Despite
      these observations, the molecular basis of leukocyte interactions with epithelial
      cells is incompletely understood. In vitro models of PMN transepithelial
      migration typically use N-formylated bacterial peptides such as fMLP in isolation
      to drive human PMNs across epithelial monolayers. However, other microbial
      products such as lipopolysaccharide (LPS) are major constituents of the
      intestinal lumen and have potent effects on the immune system. In the absence of
      LPS, we have shown that transepithelial migration requires sequential adhesive
      interactions between the PMN beta2 integrin CD11b/CD18 and JAM protein family
      members. Other epithelial ligands appear to be abundantly represented as
      fucosylated proteoglycans. Further studies indicate that the rate of PMN
      migration across mucosal surfaces can be regulated by the ubiquitously expressed
      transmembrane protein CD47 and microbial-derived factors, although many of the
      details remain unclear. Current data suggests that Toll-like receptors (TLR),
      which recognize specific pathogen-associated molecular patterns (PAMPs), are
      differentially expressed on both leukocytes and mucosal epithelial cells while
      serving to modulate leukocyte-epithelial interactions. Exposure of epithelial
      TLRs to microbial ligands has been shown to result in transcriptional
      upregulation of inflammatory mediators whereas ligation of leukocyte TLRs
      modulate specific antimicrobial responses. A better understanding of these events
      will hopefully provide new insights into the mechanisms of epithelial responses
      to microorganisms and ideas for therapies aimed at inhibiting the deleterious
      consequences of mucosal inflammation.

PMID- 15962123
TI  - Epithelial cell signaling responses to enterohemorrhagic Escherichia coli
      infection.
AB  - Enterohemorrhagic Escherichia coli, including the serotype O157:H7 that is most
      commonly identified with human disease, cause both sporadic cases and outbreaks
      of non-bloody diarrhea and hemorrhagic colitis. In about 10% of infected
      subjects, the hemolytic uremic syndrome (hemolytic anemic, thrombocytopenia, and
      acute renal failure) develops, likely as a consequence of systemic spread of
      bacterial-derived toxins variously referred to as Shiga-like toxin, Shiga toxin,
      and Verotoxin. Increasing evidence points to a complex interplay between
      bacterial products--for example, adhesins and toxins--and host signal
      transduction pathways in mediating responses to infection. Identification of
      critical signaling pathways could result in the development of novel strategies
      for intervention to both prevent and treat this microbial infection in humans.

PMID- 15962124
TI  - Good bug, bad bug: in the case of enteric inflammatory disease does the
      epithelium decide?
AB  - Many studies demonstrate that intestinal inflammation is either initiated or
      exaggerated by a component of the normal microbiota, most likely commensal
      bacteria or products derived from these organisms. We review the nature of human
      inflammatory bowel disease, the evidence for the involvement of the normal
      bacterial flora in these disorders and the relevance of maintaining the integrity
      of the epithelial barrier. Moreover, we, and others, have shown abnormal
      mitochondria structure in tissue resections from patients with inflammatory bowel
      disease and tissues from rodents that demonstrated psychological stress-induced
      increases in epithelial permeability. Thus, we also consider the possibility that
      a defect in epithelial mitochondrial function would predispose an individual to
      respond to their commensal bacteria flora--no longer considering them as a
      beneficial passive inhabitant, but rather perceiving them as a threatening and
      pro-inflammatory stimulus. In support of this postulate, we discuss our recent
      findings from an in vitro model showing that the human colon-derived T84 cell
      line exposed to the metabolic stressor, dinitrophenol, and the non-pathogenic,
      non-invasive, Escherichia coli (strain HB101) display a loss of barrier function,
      increased signal transduction and increased production of the chemokine,
      interleukin 8.

PMID- 15962125
TI  - Epithelial effects of proteinase-activated receptors in the gastrointestinal
      tract.
AB  - The intestinal epithelium plays a crucial role in providing a barrier between the
      external environment and the internal milieu of the body. A compromised mucosal
      barrier is characteristic of mucosal inflammation and is a key determinant of the
      development of intestinal diseases such as Crohn's disease and ulcerative
      colitis. The intestinal epithelium is regularly exposed to serine proteinases and
      this exposure is enhanced in numerous disease states. Thus, it is important to
      understand how proteinase-activated receptors (PARs), which are activated by
      serine proteinases, can affect intestinal epithelial function. This review
      surveys the data which demonstrate the wide distribution of PARs, particularly
      PAR-1 and PAR-2, in the gastrointestinal tract and accessory organs, focusing on
      the epithelium and those cells which communicate with the epithelium to affect
      its function. PARs have a role in regulating secretion by epithelia of the
      salivary glands, stomach, pancreas and intestine. In addition, PARs located on
      subepithelial nerves, fibroblasts and mast cells have important implications for
      epithelial function. Recent data outline the importance of the cellular site of
      PAR expression, as PARs expressed on epithelia may have effects that are
      countered by PARs expressed on other cell types. Finally, PARs and their ability
      to promote epithelial cell proliferation are discussed in terms of colon cancer.

PMID- 15962126
TI  - Beyond sepsis pathophysiology with cytokines: what is their value as biomarkers
      for disease severity?
AB  - Sepsis is a major challenge in medicine. It is a common and frequently fatal
      infectious condition. The incidence continues to increase, with unacceptably high
      mortality rates, despite the use of specific antibiotics, aggressive operative
      intervention, nutritional support, and anti-inflammatory therapies. Typically,
      septic patients exhibit a high degree of heterogeneity due to variables such as
      age, weight, gender, the presence of secondary disease, the state of the immune
      system, and the severity of the infection. We are at urgent need for biomarkers
      and reliable measurements that can be applied to risk stratification of septic
      patients and that would easily identify those patients at the highest risk of a
      poor outcome. Such markers would be of fundamental importance to decision making
      for early intervention therapy or for the design of septic clinical trials. In
      the present work, we will review current biomarkers for sepsis severity and
      especially the use of cytokines as biomarkers with important pathophysiological
      role.

PMID- 15962127
TI  - Failure of neutrophil migration toward infectious focus in severe sepsis: a
      critical event for the outcome of this syndrome.
AB  - Sepsis is a systemic inflammatory response commonly caused by bacterial
      infection. We demonstrated that the outcome of sepsis induced by cecal ligation
      and puncture (CLP) correlates with the severity of the neutrophil migration
      failure towards infectious focus. Failure appears to be due to a decrease in the
      rolling and adhesion of neutrophil to endothelium cells. It seems that neutrophil
      migration impairment is mediated by the circulating inflammatory cytokines, such
      as TNF-alpha and IL-8, which induce the nitric oxide (NO) production
      systemically. It is supported by the fact that intravenous administration of
      these cytokines reduces the neutrophil migration induced by different
      inflammatory stimuli, and in severe sepsis the circulating concentrations of the
      cytokines and chemokines are significantly increased. Moreover, the neutrophil
      migration failure and the reduction in the rolling/adhesion were not observed in
      iNOS-/- mice and, aminoguanidine prevented this event. We also demonstrated that
      the failure of neutrophil migration is a Toll-4 receptor (TLR4) dependent
      mechanism, since it was not observed in TLR4 deficient mice. Furthermore, it was
      also observed that circulating neutrophils obtained from septic patients present
      failure of neutrophil chemotaxis toward fMLP, IL-8, and LTB4 and an increased in
      sera concentrations of NO3 and cytokines. In conclusion, we demonstrated that, in
      sepsis, failure of neutrophil migration is critical for the outcome and that NO
      is involved in the process.

PMID- 15962128
TI  - Should we use antidepressants for the treatment of major depressive disorder in
      children and adolescents?

PMID- 15962129
TI  - Selective serotonin reuptake inhibitors in children and adolescents with major
      depression.

PMID- 15962130
TI  - [Post-traumatic stress in tsunami-affected areas].

PMID- 15962131
TI  - [Body dysmorphic disorder: an alternative expression of obsessive-compulsive
      disorder?].

PMID- 15962132
TI  - Behavioral inhibition and history of childhood anxiety disorders in Brazilian
      adult patients with panic disorder and social anxiety disorder.
AB  - PURPOSE: To evaluate the presence of behavioral inhibition and anxiety disorders
      during childhood in Brazilian adult patients with panic disorder and social
      anxiety disorder compared to a control group. METHODS: Fifty patients with panic
      disorder, 50 patients with social anxiety disorder, and 50 control subjects were
      included in the study. To assess the history of childhood anxiety, the Schedule
      for Affective Disorders and Schizophrenia for School Age Children, Epidemiologic
      Version (K-SADS-E), and the Diagnostic Interview for Children and Adolescents
      Parent Version (DICA-P) were used. The presence of behavioral inhibition in
      childhood was assessed by the self-reported scale of Behavioral Inhibition
      Retrospective Version (RSRI-30). RESULTS: Patients showed significantly higher
      prevalence of anxiety disorders and behavioral inhibition in childhood compared
      to the control group. Patients with social anxiety disorder also showed
      significantly higher rates of avoidance disorder (46% vs. 18%, p = 0.005), social
      anxiety disorder (60% vs. 26%, p = 0.001), presence of at least one anxiety
      disorder (82% vs. 56%, p = 0.009) and global behavioral inhibition (2.89 +/- 0.61
      vs. 2.46 +/- 0.61, p < 0.05) and school/social behavioral inhibition (3.56 +/-
      0.91 vs. 2.67 +/- 0.82, p < 0.05) in childhood compared to patients with panic
      disorder. CONCLUSION: Our data are in accordance to the literature and
      corroborates the theory of an anxiety diathesis, suggesting that a history of
      anxiety disorders in childhood is associated with an anxiety disorder diagnosis,
      mainly social anxiety disorder, in adulthood.

PMID- 15962133
TI  - Popular conceptions of schizophrenia in Cape Verde, Africa.
AB  - INTRODUCTION: It has been well documented that schizophrenia presents a better
      clinical course in developing countries. Although there are many epidemiological
      studies showing this association, little research has been conducted to
      investigate the local representation systems for schizophrenia in these
      countries. OBJECTIVES: This study focuses on cultural factors of schizophrenia,
      namely the local representation systems for the disease, as well as what is
      locally understood as deviant behavior and its acceptability, and mechanisms of
      social-cultural insertion or exclusion of patients with schizophrenia in Cape
      Verde, Africa. METHODS: Randomized open interviews were carried out with the
      relatives of patients under treatment at the mental health out patient service of
      the Batista de Sousa Hospital (Sao Vicente Island) between the years 1994 and
      1995. Interviews dealt with patients' life histories and disease related to
      problems, strategies employed by the family to cope with such problems, and
      comments on the social and family burden. RESULTS: 20 interviews with close
      relatives of 10 patients were analyzed. The study focused on three main
      categories explaining schizophrenia: "tired head" (cabeca cansada), "nervous"
      (nervoso), and supernatural categories (like "sorcery" or "witchcraft"). The
      interviewees expressed their opinions, either explicitly or not, on whether their
      relatives truly had a disease. CONCLUSION: Characteristics of local categories
      for schizophrenia found in Cape Verde can be regarded as a less stigmatized way
      of dealing with the disease. It is reasonable to suppose that the understanding
      of such cultural factors could lead to better outcomes in the treatment for
      schizophrenia in this country, and also in others, where similar conditions can
      be identified.

PMID- 15962134
TI  - The psychopathological factors of refractory schizophrenia.
AB  - OBJECTIVES: The heterogeneity of clinical manifestations in schizophrenia has
      lead to the study of symptom clusters through psychopathological assessment
      scales. The objective of this study was to elucidate clusters of symptoms in
      patients with refractory schizophrenia which may also help to assess the
      patients' therapeutical response. METHODS: Ninety-six treatment resistant
      patients were evaluated by the anchored version Brief Psychiatric Rating Scale
      (BPRS-A) as translated into Portuguese. The inter-rater reliability was 0.80. The
      18 items of the BPRS-A were subjected to exploratory factor analysis with Varimax
      rotation. RESULTS: Four factors were obtained: Negative/Disorganization, composed
      by emotional withdrawal, disorientation, blunted affect, mannerisms/posturing,
      and conceptual disorganization; Excitement, composed of excitement, hostility,
      tension, grandiosity, and uncooperativeness, grouped variables that evoke brain
      excitement or a manic-like syndrome; Positive, composed of unusual thought
      content, suspiciousness, and hallucinatory behavior; and Depressive, composed of
      depressive mood, guilt feelings, and motor retardation, clearly related to
      depressive syndrome. CONCLUSIONS: The study reproduced the four factors described
      in the literature, either in refractory or non-refractory patients. The BPRS-A
      allowed the distinction of psychopathological factors, which are important in the
      evaluation of treatment response of patients with schizophrenia.

PMID- 15962135
TI  - Factors associated with psychiatric treatment dropout in a mental health
      reference center, Belo Horizonte.
AB  - OBJECTIVE: To characterize an outpatient public referral center for mental health
      and to assess factors associated with treatment dropout. METHODS: A non
      concurrent prospective study was undertaken to review 295 patient files.
      Patients, whose first consultation took place between January and December 1997,
      were followed-up for at least four months until April 1998. Patients were
      considered as having abandoned their treatment when, following a recommendation
      for at least a second visit, they did not return within four months after the
      first consultation. Social, demographic and clinical variables were compared to
      verify possible factors associated with dropout of treatment. Statistical
      analysis was performed using relative hazard (RR) with 95% confidence interval
      (CI) estimated by the Cox Regression Model. RESULTS: Cumulative incidence of
      treatment dropout was 39.2% while multivariate analysis indicated that the
      following characteristics were statistically associated with treatment
      interruption: to live outside the referral area (RR = 1.95), no history of
      previous psychiatric hospitalizations (RR = 1.88), alcohol or drug use at
      admission (RR = 1.72), spontaneous demand to the service (RR = 2.12), lack of bus
      passes (RR = 3.68) and to have less than four clinical appointments (RR = 7.31).
      CONCLUSIONS: Our findings suggest that services should be aware of the high
      incidence of treatment interruption, especially among those with no history of
      previous psychiatric hospitalizations and with less institutional bonds. This may
      indicate that mental health services should develop and implement public policies
      targeted at this population.

PMID- 15962136
TI  - The influence of somatic symptoms on the performance of elders in the Beck
      Depression Inventory (BDI).
AB  - BACKGROUND: The Beck Depression Inventory (BDI) has been widely used to assess
      the prevalence of depressive symptomatology in clinical and non-clinical samples.
      On elders, however, the Beck Depression Inventory total score can be influenced
      by the increased scores on somatic and performance subscale due to the impact of
      ageing process itself and clinical diseases. PURPOSE: To verify if there are
      differences between answers of adults and elders for the BDI Somatic and
      Performance subscale. METHODS: Five hundred and fifty six subjects were
      interviewed. Two hundred and seventeen were adults (between 18 and 59 years old)
      and 339 were elders (> or = 60 years). Adults and elders with terminal diseases
      or dementia were excluded. The convenience sampling method was used. RESULTS:
      Elders answered significantly with higher scores in the Somatic and Performance
      subscale compared to adults (p < 0.001). Female gender and educational level were
      also associated to higher scores in the Somatic subscale. No differences between
      both age groups were found in the Cognitive-Affective subscale (p = 0.332).
      CONCLUSIONS: Positive answers in the BDI Somatic and Performance subscale must be
      carefully assessed among elder subjects. The age factor, either by aging or due
      to several diseases, can bring signs that are not necessarily symptoms of major
      depression. Further studies are suggested.

PMID- 15962137
TI  - Reliability of the Social Phobia and Anxiety Inventory (SPAI) Portuguese version
      in a heterogeneous sample of Brazilian university students.
AB  - OBJECTIVE: To evaluate internal consistency and temporal stability trough test re
      test reliability of the Portuguese version of the Social Phobia and Anxiety
      Inventory (SPAI) in a heterogeneous Brazilian sample. METHODS: After informed
      consent, the translated and adapted version of the SPAI Portuguese was tested and
      re-tested at a 14-day interval in a sample of 225 university students, both
      genders, from 4 different undergraduate courses. After double data entry,
      statistical analysis included Cronbach's alphas, Pearson and intra-class
      correlation coefficients. RESULTS: The studied sample consisted of 213 students
      from 4 sub-samples: 95 law students, 31 social communication students, 54 civil
      engineering students and 33 dental medicine students. The mean age was 23 (+/-6)
      years and 110 (51.6%) were female. The Cronbach' alpha was 0.96, no difference
      for both genders. The differential (total) score of the SPAI Portuguese showed
      Pearson coefficient 0.83 (95% CI 0.78-0.87) and Intra-class coefficient 0.83 (95%
      CI 0.78-0.86). There was no statistical difference in Pearson coefficients
      between genders (p = 0.121) and the 4 sub-samples (p = 0.258). CONCLUSION: The
      results do not ensure validity, however, the SPAI Portuguese version presented a
      good content homogeneity with satisfactory level of internal consistency. The
      temporal stability evaluated was substantial. The results showed that the
      Portuguese SPAI presents perfectly acceptable reliability for both genders and
      suggest that it can be used in Brazilian populations.

PMID- 15962138
TI  - Epidemiology of suicide in Brazil (1980-2000): characterization of age and gender
      rates of suicide.
AB  - OBJECTIVE: To describe the suicide rates in Brazil in recent decades, drawing
      comparisons with the worldwide epidemiological situation. METHODS: Descriptive
      analyses of Brazilian suicide data, relating to the 1980-2000 period and
      extracted from the DATASUS database. Brazilian suicide trends were examined by
      age and gender. RESULTS: The overall rate of suicide in Brazil increased 21% in
      20 years. Men were found to be 2.3 to 4.0 times more likely to commit suicide
      than were women, and the highest suicide rates were found in the over-65 age
      group. The greatest increase in suicide rates (1900%) was seen in the 15-24 age
      range. CONCLUSION: Brazilian suicide rates, although low, are consistent with the
      global trend toward growth. Although the highest rates are still seen among the
      elderly, members of the younger population have been killing themselves with ever
      increasing frequency.

PMID- 15962139
TI  - Prevalence of eating disorders and psychiatric comorbidity in a clinical sample
      of type 2 diabetes mellitus patients.
AB  - BACKGROUND: A few studies have shown high rates of eating disorders and
      psychiatric morbidity in patients with type 2 diabetes mellitus. OBJECTIVE:
      Disturbed eating behavior and psychiatric comorbidity in a sample of T2DM
      patients. METHODS: Seventy type 2 diabetes mellitus patients between 40 and 65
      years of age (mean, 52.9 +/- 6.8) from a diabetes outpatient clinic were
      sequentially evaluated. The Structured Clinical Interview for DSM-IV, Binge
      Eating Scale and Beck Depression Inventory were used to assess eating disorders
      and other psychiatric comorbidity. In addition to the descriptive analysis of the
      data, we compared groups divided based on the presence of obesity (evaluated by
      the body mass index) or an eating disorder. RESULTS: Twenty percent of the sample
      displayed an eating disorder. Binge eating disorder was the predominant eating
      disorder diagnosis (10%). Overall, the group of obese patients with type 2
      diabetes mellitus presented rates of psychiatric comorbidity comparable to those
      seen in their nonobese counterparts. However, the presence of an eating disorder
      was associated with a significant increase in the frequency of anxiety disorders
      (57.1% x 28.6%; p = 0.044). CONCLUSIONS: In our study sample, the occurrence of
      eating disorders was increased compared to rates observed in the general
      population, with the predominance of binge eating disorder. The presence of an
      eating disorder in type 2 diabetes mellitus patients was associated with higher
      rates of anxiety disorders.

PMID- 15962140
TI  - Clinical expression of obsessive-compulsive disorder in women with bipolar
      disorder.
AB  - OBJECTIVE: To study clinical and psychopathological features of obsessive
      compulsive disorder (OCD) in women with bipolar disorder (BD). METHODS: Fifteen
      outpatients with concurrent bipolar disorder I (80.0%) or II (20.0%) and
      obsessive-compulsive disorder were studied. Most of them (80.0%) sought treatment
      for bipolar disorder. They were ascertained by means of the Structured Clinical
      Interview for DSM-IV (SCID/P), semi-structured interviews to investigate
      obsessions, compulsions and sensory phenomena that may precede compulsions and an
      additional module for the diagnosis of chronic motor and vocal tics. Severity of
      symptoms was assessed by the Yale-Brown Obsessive-Compulsive Rating Scale,
      Hamilton Depression Rating Scale and Young Mania Rating Scale. RESULTS: Obsessive
      compulsive disorder presented early onset (before the age of 10) in 9 (60%)
      cases, preceded bipolar disorder in 10 (66.7%) and displayed chronic waxing and
      waning course in 13 (86.7%) of them. There was wide overlap between types of
      obsessive-compulsive symptoms and all patients experienced sensory phenomena
      preceding the compulsions. There was no clear-cut impact of depressive and manic
      episodes on the intensity of obsessive-compulsive symptoms, which increased in
      depression and decreased in mania in 40.0% of the cases, had the opposite pattern
      in 26.7% of the patients and fluctuated inconsistently in the rest of them. Tics
      disorders were diagnosed in 5 (33.3%) patients. CONCLUSIONS: Our results suggest
      that in women with comorbid bipolar disorder and obsessive-compulsive disorder
      the latter presents features that may be typical of the association of the two
      disorders, such as early onset and sensory phenomena preceding compulsions. A
      prospective controlled study is necessary to confirm these observations, due to
      some limitations of our study: small exclusively female sample, heterogeneity
      concerning the type of bipolar disorder and the disorder that determined sought
      of treatment and retrospective non-controlled design.

PMID- 15962141
TI  - Translation, adaptation and reliability study of the Scale to Assess Unawareness
      of Mental Disorder--SUMD.
AB  - INTRODUCTION: Previous studies have suggested that lack of insight into mental
      disorder can be an important predicting factor involving the course of psychotic
      disorders mainly regarding compliance with treatment. The Scale to Assess
      Unawareness of Mental Disorder--SUMD is a semi-structured open interview that
      evaluates global insight, insight into illness and insight into symptoms. The
      SUMD has shown good reliability and validity and has demonstrated certain
      advantages over previous measures of insight, suggesting the usefulness of a
      multidimensional view of this complex concept. OBJECTIVE: The aim of this study
      is to translate, adapt and test the reliability of the SUMD in schizophrenic
      patients. METHODS: This study involved 35 schizophrenic patients according to the
      DSM-IV criteria, who where under treatment in the Schizophrenia Program of the
      Federal University of Sao Paulo. Two independent examiners conducted the
      reliability study simultaneously. RESULTS: The results demonstrated that the SUMD
      achieved a good intraclass reliability coefficients between investigators--ICC
      ranged from 0.55 to 0.97--for the general items to assess awareness of mental
      disorder and 0.56 to 0.98--for the symptoms items. DISCUSSION: These coefficients
      were similar to those found by the researchers who developed this scale. The SUMD
      scale has proven to be easily applied and may be deemed an useful instrument with
      good psychometrics capacities in researches involving schizophrenic subjects.

PMID- 15962142
TI  - [Basic concepts in epidemiology and statistics for reading controlled clinical
      trials].
AB  - The authors present the basic concepts in epidemiology and statistics needed for
      understanding properly the design and results of controlled clinical trials.
      Through a set of examples, the concepts of measures of association and effect,
      statistical significance tests, p-value, confidence interval and statistical
      power are presented and common their misinterpretations are discussed.

PMID- 15962143
TI  - [The De Clerambault's syndrome: a bibliographic revision].
AB  - De Clerambault's syndrome (or erotomania) consists in a delusional conviction, by
      the patient, in which someone of higher social status has fallen in love with him
      or her. Sexual privation can be an important psychodynamic factor on the
      development of this condition, but organic factors related to its genesis
      continue on investigation. This study revises the most important aspects that the
      literature brings us about this disease and its causes. The databases MEDLINE and
      LILACS have been consulted, and the most appropriate articles were examined. It
      is established that erotomania is not much found in the scientific literature,
      and, probably, it isn't as rare as it has been proposed. The major part of its
      etiologic explanation is based on psychodynamic factors, without, however,
      confirmed relation of cause with its clinic presentation. The progress in the
      neurobiologic researches will improve, perhaps, the accuracy of diagnose and
      treatment of these patients.

PMID- 15962144
TI  - [Descriptive psychopathology: is there a common language?].
AB  - We elaborated a review of some of the main books of descriptive psychopathology,
      Brazilian and international ones, with the objective of examining if there is
      uniformity among the various authors about concepts and terminology. We observed
      that there is not truly a common language: some concepts are used by some authors
      but are ignored by others; a same term is utilized with different meanings; and a
      same concept is assigned by different terms. Here some points of divergence among
      the various authors are presented and discussed.

PMID- 15962146
TI  - Organic vs. psychogenic tics.

PMID- 15962147
TI  - [Myocardial disease in a patient treated with clozapine].

PMID- 15962148
TI  - [Frequency of epilepsy in psychiatric inpatients].

PMID- 15962149
TI  - [Psycho-educational intervention in mood disorders: an experience of Affective
      Disorders Study Group].

PMID- 15962150
TI  - [Depressive symptoms and death in acute ischemic coronary syndromes].

PMID- 15962153
TI  - [1st Brazilian Congress of Epidemiology].

PMID- 15962154
TI  - [Genetic epidemiology: epidemiology, genetics or none of them?].
AB  - In an attempt to contribute to a better understanding of the identity of Genetic
      Epidemiology, we review its conception, its field of influence, its appropriate
      methods and techniques and, at last, some of its applications. Genetic
      Epidemiology involves the study of genetic factors acting on diseases and on
      their environmental interactions. These includes two major areas: a descriptive
      one, related to the distribution of such conditions in families and populations,
      to the epidemiologic surveillance and to the study of determinants; and another
      characterized by intervention, which is related to preventive measures. Because
      of the difficulty in considering all possible situations, especial attention is
      given to review some converging epidemiological and genetical methods and
      techniques. Among them, we stress the case studies on lab methodologies, as
      dermatoglyphics, and on quantitative procedures, as path analysis. Some studies
      are taken as examples for application, since they have been object of research in
      our country: leprosy, hydrargyrism and schizophrenia.

PMID- 15962155
TI  - [The rights to health information].
AB  - This article discusses the role of the press in the diffusion of health
      information during an epidemics outbreak. After having analysed the news
      published at the Sao Paulo City press since January 1988, we identified some
      patterns of behavior by health authorities and by the press. The right to
      information is discussed in relation to the construction of a critical health
      awareness which allows social groups to act when facing health situation of
      potential threat.

PMID- 15962156
TI  - [Social equity in the health domain].
AB  - In the European debate on equity in health and health care a crucial question has
      received scant consideration. It concerns the precise specification of a health
      system's objectives and the manner by which they can be suitably interpreted to
      permit monitoring of implemented policies. This article is an attempt to review
      actual and potential contributions to this area of study. It adopts the view that
      the meaning of equity in the health domain depends crucially on how social
      justice is defined and that this in turn depends on value judgements or the views
      of society held by individuals, groups or governments. Such an approach allows
      one to choose principles of distribution which are in agreement with a society's
      value set and subsequently to apply them as the correct yardstick for measuring
      the success of policy. Following an initial exposition of the approach, the main
      body of the article discusses the question of competing theories of society -
      Libertarian, Liberal and Democratic Socialist - and appraises the various
      distribution principles, to be found in the economic and philosophical
      literature, which they imply. The final section offers some brief conclusions and
      avenues for further research.

PMID- 15962157
TI  - [New technologies, occupational medicine and health].
AB  - The present article deals with the health effects and social aspects associated
      with the introduction of modern microelectronic technologies within work
      processes, particularly in the Federal Republic of Germany. The author makes
      considerations on some theoretical limitations of Occupational Medicine in order
      to analyse and avert problems resulting from these processes.

PMID- 15962158
TI  - [Professional training in biology: its relationships with animal experimentation
      and environmental protection].
AB  - With reference to the controversy regarding animal experimentation, this article
      questions the relationship with the professional training in universities. The
      considerations voiced in the paper are based on data gathered from interviews
      with students and professors of Biological Science courses at two different
      universities in Sao Paulo. These data reveal that the use of animals is not seen
      as an ethical problem by most of the people interviewed and, also, that there
      exists a high degree of unfamiliarity with the laws, principles and techniques
      recommended for animal experimentation. It is also suggested that this situation
      springs from a class orientation and predominance of a technician tendency geared
      toward professionalization, which in turn is subordinated to market demands, in
      university teaching.

PMID- 15962159
TI  - [Evaluating children health conditions in a small community: the study of
      Itapirapua, Ribeira Valley, SP].
AB  - A household survey for evaluating the mortality, morbidity, nutritional status
      and health services utilization of children aged under five years was carried out
      in a rural village in Ribeira, Sao Paulo State. Most children belonged to
      families of rural laborers earning less than 80 US dollars per month and living
      under inadequate environmental conditions. The infant mortality rate was equal to
      83 per thousand and 35% of the children were affected by moderate or severe
      stunting, rates which are well above those for the State. The main reasons for
      clinic attendances and hospital admissions were acute respiratory infections and
      diarrhea. The median duration of breastfeeding was 14.4 months, the highest
      reported for Brazil. Only 40% of the mothers had received antenatal care, and 56%
      delivered in a hospital - of whom 35% had a caesarean section. Vaccine coverage
      reached 65% of children aged 12 months or more. This survey revealed an enclave
      of high morbidity and mortality within Brazil's richest state. It also showed
      that with a limited budget and within a short time it is possible to obtain
      valuable information for planning child survival strategies.

PMID- 15962160
TI  - [Water measurement taxation - an opinion from United Kingdom].

PMID- 15962162
TI  - [Echos from the 1st Brazilian Congress of Epidemiology].

PMID- 15962161
TI  - [Homeless children in Brazil].

PMID- 15962173
TI  - Genotoxic, neurotoxic and neuroprotective activities of apomorphine and its
      oxidized derivative 8-oxo-apomorphine.
AB  - Apomorphine is a dopamine receptor agonist proposed to be a neuroprotective agent
      in the treatment of patients with Parkinson's disease. Both in vivo and in vitro
      studies have shown that apomorphine displays both antioxidant and pro-oxidant
      actions, and might have either neuroprotective or neurotoxic effects on the
      central nervous system. Some of the neurotoxic effects of apomorphine are
      mediated by its oxidation derivatives. In the present review, we discuss recent
      studies from our laboratory in which the molecular, cellular and neurobehavioral
      effects of apomorphine and its oxidized derivative, 8-oxo-apomorphine-semiquinone
      (8-OASQ), were evaluated in different experimental models, i.e., in vitro
      genotoxicity in Salmonella/microsome assay and WP2 Mutoxitest, sensitivity assay
      in Saccharomyces cerevisiae, neurobehavioral procedures (inhibition avoidance
      task, open field behavior, and habituation) in rats, stereotyped behavior in
      mice, and Comet assay and oxidative stress analyses in mouse brain. Our results
      show that apomorphine and 8-OASQ induce differential mutagenic, neurochemical and
      neurobehavioral effects. 8-OASQ displays cytotoxic effects and oxidative and
      frameshift mutagenic activities, while apomorphine shows antimutagenic and
      antioxidant effects in vitro. 8-OASQ induces a significant increase of DNA damage
      in mouse brain tissue. Both apomorphine and 8-OASQ impair memory for aversive
      training in rats, although the two drugs showed a different dose-response
      pattern. 8-OASQ fails to induce stereotyped behaviors in mice. The implications
      of these findings are discussed in the light of evidence from studies by other
      groups. We propose that the neuroprotective and neurotoxic effects of dopamine
      agonists might be mediated, in part, by their oxidized metabolites.

PMID- 15962174
TI  - Early effects of estrogen on the rat ventral prostate.
AB  - Complex interactions between androgen and estrogen (E2) regulate prostatic
      development and physiology. We analyzed the early effects of a high single dose
      of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult
      90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight,
      and the variation in the relative and absolute volume of tissue compartments and
      apoptotic indices were determined for 7 days. Castration and exogenous E2
      markedly reduced ventral prostate weight (about 50% of the control), with a
      significant reduction in the epithelial compartment and increased stroma. The
      final volume of the epithelium was identical at day 7 for all treatments (58.5%
      of the control). However, E2 had an immediate effect, causing a reduction in
      epithelial volume as early as day 1. An increase in smooth muscle cell volume
      resulted from the concentration of these cells around the regressing epithelium.
      The treatments resulted in differential kinetics in epithelial cell apoptosis.
      Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells
      presenting signs of apoptosis, whereas E2 caused an immediate increase (observed
      on day 1) and a sustained (up to day 7) effect. E2 administration to castrated
      rats significantly increased the level of apoptosis by day 3, reaching 9% of the
      epithelial cells. The divergent kinetics between treatments resulted in the same
      levels of epithelial regression after 7 days (approximately 30% of control).
      These results show that E2 has an immediate and possibly direct effect on the
      prostate, and anticipates epithelial cell death before reducing testosterone to
      levels as low as those of castrated rats. In addition, E2 and androgen
      deprivation apparently cause epithelial cell death by distinct and independent
      pathways.

PMID- 15962175
TI  - Cardiovascular actions of angiotensin-(1-7).
AB  - Angiotensin-(1-7) (Ang-(1-7)) is now considered to be a biologically active
      member of the renin-angiotensin system. The functions of Ang-(1-7) are often
      opposite to those attributed to the main effector component of the renin
      angiotensin system, Ang II. Chronic administration of angiotensin-converting
      enzyme inhibitors (ACEI) increases 10- to 25-fold the plasma levels of this
      peptide, suggesting that part of the beneficial effects of ACEI could be mediated
      by Ang-(1-7). Ang-(1-7) can be formed from Ang II or directly from Ang I. Other
      enzymatic pathways for Ang-(1-7) generation have been recently described
      involving the novel ACE homologue ACE2. This enzyme can form Ang-(1-7) from Ang
      II or less efficiently by the hydrolysis of Ang I to Ang-(1-9) with subsequent
      Ang-(1-7) formation. The biological relevance of Ang-(1-7) has been recently
      reinforced by the identification of its receptor, the G-protein-coupled receptor
      Mas. Heart and blood vessels are important targets for the formation and actions
      of Ang-(1-7). In this review we will discuss recent findings concerning the
      biological role of Ang-(1-7) in the heart and blood vessels, taking into account
      aspects related to its formation and effects on these tissues. In addition, we
      will discuss the potential of Ang-(1-7) and its receptor as a target for the
      development of new cardiovascular drugs.

PMID- 15962176
TI  - Recombinant viruses as vaccines against viral diseases.
AB  - Vaccine approaches to infectious diseases are widely applied and appreciated.
      Amongst them, vectors based on recombinant viruses have shown great promise and
      play an important role in the development of new vaccines. Many viruses have been
      investigated for their ability to express proteins from foreign pathogens and
      induce specific immunological responses against these antigens in vivo.
      Generally, gene-based vaccines can stimulate potent humoral and cellular immune
      responses and viral vectors might be an effective strategy for both the delivery
      of antigen-encoding genes and the facilitation and enhancement of antigen
      presentation. In order to be utilized as a vaccine carrier, the ideal viral
      vector should be safe and enable efficient presentation of required pathogen
      specific antigens to the immune system. It should also exhibit low intrinsic
      immunogenicity to allow for its re-administration in order to boost relevant
      specific immune responses. Furthermore, the vector system must meet criteria that
      enable its production on a large-scale basis. Several viral vaccine vectors have
      thus emerged to date, all of them having relative advantages and limits depending
      on the proposed application, and thus far none of them have proven to be ideal
      vaccine carriers. In this review we describe the potential, as well as some of
      the foreseeable obstacles associated with viral vaccine vectors and their use in
      preventive medicine.

PMID- 15962177
TI  - Partial characterization and anticoagulant activity of a heterofucan from the
      brown seaweed Padina gymnospora.
AB  - The brown algae Padina gymnospora contain different fucans. Powdered algae were
      submitted to proteolysis with the proteolytic enzyme maxataze. The first extract
      of the algae was constituted of polysaccharides contaminated with lipids,
      phenols, etc. Fractionation of the fucans with increasing concentrations of
      acetone produced fractions with different proportions of fucose, xylose, uronic
      acid, galactose, and sulfate. One of the fractions, precipitated with 50% acetone
      (v/v), contained an 18-kDa heterofucan (PF1), which was further purified by gel
      permeation chromatography on Sephadex G-75 using 0.2 M acetic acid as eluent and
      characterized by agarose gel electrophoresis in 0.05 M 1,3 diaminopropane/acetate
      buffer at pH 9.0, methylation and nuclear magnetic resonance spectroscopy.
      Structural analysis indicates that this fucan has a central core consisting
      mainly of 3-beta-D-glucuronic acid 1-> or 4-beta-D-glucuronic acid 1 ->,
      substituted at C-2 with alpha-L-fucose or beta-D-xylose. Sulfate groups were only
      detected at C-3 of 4-alpha-L-fucose 1-> units. The anticoagulant activity of the
      PF1 (only 2.5-fold lesser than low molecular weight heparin) estimated by
      activated partial thromboplastin time was completely abolished upon desulfation
      by solvolysis in dimethyl sulfoxide, indicating that 3-O-sulfation at C-3 of 4
      alpha-L-fucose 1-> units is responsible for the anticoagulant activity of the
      polymer.

PMID- 15962178
TI  - APOA1/C3/A4 gene cluster variability and lipid levels in Brazilian children.
AB  - Genetic studies have suggested that polymorphisms of genes coding for
      apolipoproteins are significant determinants of serum lipoprotein and lipid
      levels in adults. However, only a few studies have investigated the association
      of these polymorphisms in children. Therefore, in the present investigation we
      studied the distribution of APOA1 -75 G>A, +83 C>T, APOC3 -482 C>T, -455 T>C and
      3238 C>G, and APOA4 Q360H and T347S polymorphisms and their influence on plasma
      lipoprotein levels in children from a Brazilian northeastern admixed population.
      The seven polymorphic sites were genotyped in 414 children aged 5 to 15 years
      (mean 8.9 +/- 2.9). The genotypes of the seven polymorphic sites were assessed by
      PCR-RFLP methods. The frequencies of the less common alleles were, in general,
      intermediate among parental populations, as expected. Strong linkage
      disequilibrium was detected between polymorphisms at the APOA1, APOC3 and APOA4
      loci in this admixed population sample. Overall the genotype effects seen in
      adults were weaker or absent in children. The APOC3/-455 and APOA4 T347S variants
      showed significant effects on HDL cholesterol in girls (P = 0.033 and P = 0.016,
      respectively). Significantly higher plasma total (P = 0.003) and LDL cholesterol
      (P = 0.004) levels were observed in boys who were carriers of the 3238G allele at
      the APOC3/3238 C>G site. These results disclosed an overall absence of
      associations between these polymorphisms and lipids in children. This finding is
      not unexpected because expression of the effect of these polymorphisms might
      depend on the interaction with environmental variables both internal and external
      to the individual.

PMID- 15962179
TI  - Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory
      drugs on the production of reactive oxygen species by activated rat neutrophils.
AB  - The release of reactive oxygen specie (ROS) by activated neutrophil is involved
      in both the antimicrobial and deleterious effects in chronic inflammation. The
      objective of the present investigation was to determine the effect of therapeutic
      plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) on the
      production of ROS by stimulated rat neutrophils. Diclofenac (3.6 microM),
      indomethacin (12 microM), naproxen (160 microM), piroxicam (13 microM), and
      tenoxicam (30 microM) were incubated at 37 masculineC in PBS (10 mM), pH 7.4, for
      30 min with rat neutrophils (1 x 10(6) cells/ml) stimulated by phorbol-12
      myristate-13-acetate (100 nM). The ROS production was measured by luminol and
      lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS
      production: 58 +/- 2% diclofenac, 90 +/- 2% indomethacin, 33 +/- 3% piroxicam,
      and 45 +/- 6% tenoxicam (N = 6). For the lucigenin assay, naproxen, piroxicam and
      tenoxicam were ineffective. For indomethacin the inhibition was 52 +/- 5% and
      diclofenac showed amplification in the light emission of 181 +/- 60% (N = 6).
      Using the myeloperoxidase (MPO)/H2O2/luminol system, the effects of NSAIDs on MPO
      activity were also screened. We found that NSAIDs inhibited both the peroxidation
      and chlorinating activity of MPO as follows: diclofenac (36 +/- 10, 45 +/- 3%),
      indomethacin (97 +/- 2, 100 +/- 1%), naproxen (56 +/- 8, 76 +/- 3%), piroxicam
      (77 +/- 5, 99 +/- 1%), and tenoxicam (90 +/- 2, 100 +/- 1%), respectively (N =
      3). These results show that therapeutic levels of NSAIDs are able to suppress the
      oxygen-dependent antimicrobial or oxidative functions of neutrophils by
      inhibiting the generation of hypochlorous acid.

PMID- 15962180
TI  - Morphological changes induced by testosterone in the mammary glands of female
      Wistar rats.
AB  - Increased levels of androgens in postmenopausal women are considered to be a risk
      factor for breast cancer. Testosterone, alone or in combination with estrogen,
      induces epithelial dysplasia and mammary tumors in Noble rats. Since this model
      of hormone-induced neoplasia has not been reported in other rat strains, we
      studied the effect of testosterone on the mammary gland morphology of female
      Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the
      dorsum midline with a silicone tube containing 50 mg testosterone (testosterone
      propionate in 30 animals and non-esterified testosterone in the remaining 30
      animals) and 20 additional animals were implanted with empty tubes and used as
      control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days
      after implantation, and the mammary glands were dissected, fixed and embedded in
      paraffin. Histological sections were then stained with hematoxylin and eosin and
      picrosyrius red for collagen visualization. Morphological and morphometric
      analysis demonstrated ductal proliferation and acinotubular differentiation with
      secretory activity in all treated animals, peaking at 90 days of androgen
      exposure. After 90 days the proliferation of acinar epithelial cells was evident,
      but there was a progressive reduction of secretory differentiation and an
      increase in intralobular collagen fibers. There was no morphological evidence of
      dysplastic changes or other pre-neoplastic lesions. Testosterone treatment
      applied to adult, non-castrated female Wistar rats induced a mammary gland
      hyperplasia resembling the lactating differentiation, with progressive reduction
      in secretory differentiation.

PMID- 15962181
TI  - Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration.
AB  - Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle
      regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear
      whether calcineurin preferentially affects the regeneration of slow- or fast
      twitch muscles. We investigated the effect of a calcineurin inhibitor,
      cyclosporin A (CsA), on the morphology and fiber diameter of regenerating slow-
      and fast-twitch muscles. Adult Wistar rats (259.5 +/- 9 g) maintained under
      standard conditions were treated with CsA (20 mg/kg body weight, ip) for 5 days,
      submitted to cryolesion of soleus and tibialis anterior (TA) muscles on the 6th
      day, and then treated with CsA for an additional 21 days. The muscles were
      removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter
      the body weight gain of the animals after 21 days of regeneration (P = 0.001) and
      CsA significantly reduced the body weight gain (15.5%; P = 0.01) during the same
      period. All treated TA and soleus muscles showed decreased weights (17 and 29%,
      respectively, P < 0.05). CsA treatment decreased the cross-sectional area of both
      soleus and TA muscles of cryoinjured animals (TA: 2108 +/- 930 vs 792 +/- 640
      microm(2); soleus: 2209 +/- 322 vs 764 +/- 439 m(2); P < 0.001). Histological
      sections of both muscles stained with Toluidine blue revealed similar
      regenerative responses after cryolesion. In addition, CsA was able to minimize
      these responses, i.e., centralized nuclei and split fibers, more efficiently so
      in TA muscle. These results indicate that calcineurin preferentially plays a role
      in regeneration of slow-twitch muscle.

PMID- 15962182
TI  - Relationships between fetal body weight of Wistar rats at term and the extent of
      skeletal ossification.
AB  - We investigated the relationship between fetal body weight at term (pregnancy day
      21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges
      (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal
      vertebrae in Wistar rats. The relationships between fetal body weight and sex,
      intrauterine position, uterine horn, horn size, and litter size were determined
      using historical control data (7594 fetuses; 769 litters) of untreated rats.
      Relationships between body weight and degree of ossification were examined in a
      subset of 1484 historical control fetuses (154 litters) which were subsequently
      cleared and stained with alizarin red S. Fetal weight was independent of horn
      size, uterine horn side (left or right) or intrauterine position. Males were
      heavier than females and fetal weight decreased with increasing litter size.
      Evaluation of the skeleton showed that ossification of sternum, metacarpus and
      metatarsus was extensively complete and independent of fetal weight on pregnancy
      day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges
      and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight.
      The strongest correlation between body weight and degree of ossification was
      found for hindlimb, medial and proximal phalanges. Our data therefore suggest
      that, in full-term rat fetuses (day 21), reduced ossification of sternum,
      metacarpus and metatarsus results from a localized impairment of bone
      calcification (i.e., a malformation or variation) rather than from general growth
      retardation and that ossification of hindlimb (medial and proximal) phalanges is
      a good indicator of treatment-induced fetal growth retardation.

PMID- 15962183
TI  - Effect of an isotonic rehydration sports drink and exercise on urolithiasis in
      rats.
AB  - The objective of the present study was to evaluate the role of physical exercise
      as well as the influence of hydration with an isotonic sports drink on renal
      function in male Wistar rats. Four groups were studied over a period of 42 days:
      1) control (N = 9); 2) physical exercise (Exe, N = 7); 3) isotonic drink (Drink,
      N = 8); 4) physical exercise + isotonic drink (Exe + Drink, N = 8). Physical
      exercise consisted of running on a motor-driven treadmill for 1 h/day, at 20
      m/min, 5 days a week. The isotonic sports drink was a commercial solution used by
      athletes for rehydration after physical activity, 2 ml administered by gavage
      twice a day. Urine cultures were performed in all animals. Twenty-four-hour urine
      samples were collected in metabolic cages at the beginning and at the end of the
      protocol period. Urinary and plasma parameters (sodium, potassium, urea,
      creatinine, calcium) did not differ among groups. However, an amorphous material
      was observed in the bladders of animals in the Exe + Drink and Drink groups.
      Characterization of the material by Western blot revealed the presence of Tamm
      Horsfall protein and angiotensin converting enzyme. Physical exercise and the
      isotonic drink did not change the plasma or urinary parameters measured. However,
      the isotonic drink induced the formation of intravesical matrix, suggesting a
      potential lithogenic risk.

PMID- 15962184
TI  - Can organic and transgenic soy be used as a substitute for animal protein by
      rats?
AB  - We evaluated the protein quality of organic and transgenic soy fed to rats
      throughout life. Thirty female Wistar rats were divided into three groups (N =
      10): organic soy group (OSG) receiving organic soy-based diet, genetically
      modified soy group (GMSG) receiving transgenic soy-based diet, and a control
      group (CG) receiving casein-based diet. All animals received water and isocaloric
      diet (10% protein), ad libitum for 291 days. After this, the weight of GMSG
      animals (290.9 +/- 9.1 g) was significantly lower (P <= 0.04) than CG (323.2 +/-
      7.9 g). The weight of OSG (302.2 +/- 8.7 g) was between that of the GMSG and the
      CG. Protein intake was similar for OSG (308.4 +/- 6.8 g) and GMSG (301.5 +/- 2.5
      g), and significantly lower (P <= 0.0005) than the CG (358.4 +/- 8.1 g). Growth
      rate was similar for all groups: OSG (0.80 +/- 0.02 g), GMSG (0.81 +/- 0.03 g)
      and CG (0.75 +/- 0.02 g). In addition to providing a good protein intake and
      inducing less weight gain, both types of soy were utilized in a manner similar to
      that of casein, suggesting that the protein quality of soy is similar to that of
      the standard protein casein. The groups fed soy-based diet gained less weight,
      which may be considered to be beneficial for health. We conclude that organic and
      transgenic soy can be fed throughout life to rats in place of animal protein,
      because contain high quality protein and do not cause a marked increase in body
      weight.

PMID- 15962185
TI  - Humoral response to low molecular weight antigens of Mycobacterium tuberculosis
      by tuberculosis patients and contacts.
AB  - Much effort has been devoted to the identification of immunologically important
      antigens of Mycobacterium tuberculosis and to the combination of target antigens
      to which antibodies from serum of tuberculous patients could react specifically.
      We searched for IgG antibodies specific for antigens of 45 to 6 kDa obtained
      after sonication of the well-characterized wild M. tuberculosis strain in order
      to detect differences in the antibody response to low molecular weight antigens
      from M. tuberculosis between patients with pulmonary tuberculosis and contacts.
      Specific IgG antibodies for these antigens were detected by Western blot analysis
      of 153 serum samples collected from 51 patients with confirmed pulmonary
      tuberculosis. Three samples were collected from each patient: before therapy, and
      after 2 and 6 months of treatment. We also analyzed 25 samples obtained from
      contacts, as well as 30 samples from healthy individuals with known tuberculin
      status, 50 samples from patients with other lung diseases and 200 samples from
      healthy blood donors. The positive predictive value for associated IgG reactivity
      against the 6-kDa and 16-kDa antigens, 6 and 38 kDa, and 16 and 38 kDa was 100%
      since simultaneous reactivity for these antigens was absent in healthy
      individuals and individuals with other lung diseases. This association was
      observed in 67% of the patients, but in only 8% of the contacts. The humoral
      response against antigens of 16 and 6 kDa seems to be important for the detection
      of latent tuberculosis since the associated reactivity to these antigens is
      mainly present in individuals with active disease.

PMID- 15962186
TI  - Maternal aggression in Wistar rats: effect of 5-HT2A/2C receptor agonist and
      antagonist microinjected into the dorsal periaqueductal gray matter and medial
      septum.
AB  - The objective of the present study was to assess the role of the 5-HT2A/2C
      receptor at two specific brain sites, i.e., the dorsal periaqueductal gray matter
      (DPAG) and the medial septal (MS) area, in maternal aggressive behavior after the
      microinjection of either a 5-HT2A/2C receptor agonist or antagonist. Female
      Wistar rats were microinjected on the 7th postpartum day with the selective
      agonist alpha-methyl-5-hydroxytryptamine maleate (5-HT2A/2C) or the antagonist 5
      HT2A/2C, ketanserin. The agonist was injected into the DPAG at 0.2 (N = 9), 0.5
      (N = 10), and 1.0 microg/0.2 microl (N = 9), and the antagonist was injected at
      1.0 microg/0.2 microl (N = 9). The agonist was injected into the medial septal
      area (MS) at 0.2 (N = 9), 0.5 (N = 7), and 1.0 microg/0.2 microl (N = 6) and the
      antagonist was injected at 1.0 microg/0.2 microl (N = 5). For the control, saline
      was injected into the DPAG (N = 7) and the MS (N = 12). Both areas are related to
      aggressive behavior and contain a high density of 5-HT receptors. Non-aggressive
      behaviors such as horizontal locomotion (walking) and social investigation and
      aggressive behaviors such as lateral threat (aggressive posture), attacks
      (frontal and lateral), and biting the intruder were analyzed when a male intruder
      was placed into the female resident's cage. For each brain area studied, the
      frequency of the behaviors was compared among the various treatments by analysis
      of variance. The results showed a decrease in maternal aggressive behavior
      (number of bites directed at the intruder) after microinjection of the agonist at
      0.2 and 1.0 microg/0.2 microl (1.6 +/- 0.7 and 0.9 +/- 0.3) into the DPAG
      compared to the saline group (5.5 +/- 1.1). There was no dose-response
      relationship with the agonist. The present findings suggest that the 5-HT2A/2C
      receptor agonist has an inhibitory effect on maternal aggressive behavior when
      microinjected into the DPAG and no effect when microinjected into the MS.
      Ketanserin (1.0 microg/0.2 microl) decreased locomotion when microinjected into
      the DPAG and MS, but did not affect aggressive behavior. We interpret these
      findings as evidence for a specific role of 5-HT2A/2C receptors in the DPAG in
      the inhibition of female aggressive behavior, dissociated from those on motor
      activity.

PMID- 15962187
TI  - Influence of melatonin on the development of functional nicotinic acetylcholine
      receptors in cultured chick retinal cells.
AB  - The influence of melatonin on the developmental pattern of functional nicotinic
      acetylcholine receptors was investigated in embryonic 8-day-old chick retinal
      cells in culture. The functional response to acetylcholine was measured in
      cultured retina cells by microphysiometry. The maximal functional response to
      acetylcholine increased 2.7 times between the 4th and 5th day in vitro (DIV4,
      DIV5), while the Bmax value for [125I]-alpha-bungarotoxin was reduced. Despite
      the presence of alpha8-like immunoreactivity at DIV4, functional responses
      mediated by alpha-bungarotoxin-sensitive nicotinic acetylcholine receptors were
      observed only at DIV5. Mecamylamine (100 microM) was essentially without effect
      at DIV4 and DIV5, while dihydro-ss-erythroidine (10-100 microM) blocked the
      response to acetylcholine (3.0 nM-2.0 microM) only at DIV4, with no effect at
      DIV5. Inhibition of melatonin receptors with the antagonist luzindole, or
      melatonin synthesis by stimulation of D4 dopamine receptors blocked the
      appearance of the alpha-bungarotoxin-sensitive response at DIV5. Therefore, alpha
      bungarotoxin-sensitive receptors were expressed in retinal cells as early as at
      DIV4, but they reacted to acetylcholine only after DIV5. The development of an
      alpha-bungarotoxin-sensitive response is dependent on the production of melatonin
      by the retinal culture. Melatonin, which is produced in a tonic manner by this
      culture, and is a key hormone in the temporal organization of vertebrates, also
      potentiates responses mediated by alpha-bungarotoxin-sensitive receptors in rat
      vas deferens and cerebellum. This common pattern of action on different cell
      models that express alpha-bungarotoxin-sensitive receptors probably reflects a
      more general mechanism of regulation of these receptors.

PMID- 15962188
TI  - A routine electrocardiogram cannot be used to determine the size of myocardial
      infarction in the rat.
AB  - Nine lead electrocardiograms of non-infarcted (N = 61) and infarcted (N = 71)
      female Wistar rats (200-250 g) were analyzed in order to distinguish left
      ventricle myocardial infarction (MI) larger than 40% (LMI) from MI smaller than
      40% (SMI). MI larger than 40% clearly caused a deviation of AQRS and AT from
      normal values of 270-360 degrees to 90-270 degrees. Infarcted rats showed Q wave
      in D1 larger than 1 mm with 94% sensitivity and 100% specificity. The sum of QRS
      positivity in V1, V2 and V6 lower than 10 mm identified MI with 82% sensitivity
      and 100% specificity. The data showed that MI can be easily and reliably
      diagnosed by electrocardiogram in the rat. However, contradicting what is
      frequently believed, when specificity and sensitivity were analyzed focusing on
      MI size, none of these current electrocardiographic indices of MI size adequately
      discriminates LMI from SMI.

PMID- 15962189
TI  - Subacute effects of a maximal exercise bout on endothelium-mediated vasodilation
      in healthy subjects.
AB  - We evaluated vascular reactivity after a maximal exercise test in order to
      determine whether the effect of exercise on the circulation persists even after
      interruption of the exercise. Eleven healthy sedentary volunteers (six women, age
      28 +/- 5 years) were evaluated before and after (10, 60, and 120 min) a maximal
      exercise test on a treadmill. Forearm blood flow (FBF) was measured by venous
      occlusion plethysmography before and during reactive hyperemia (RH). Baseline
      FBF, analyzed by the area under the curve, increased only at 10 min after
      exercise (P = 0.01). FBF in response to RH increased both at 10 and 60 min vs
      baseline (P = 0.004). Total excess flow for RH above baseline showed that
      vascular reactivity was increased up to 60 min after exercise (mean +/- SEM,
      before: 526.4 +/- 48.8; 10 min: 1053.0 +/- 168.2; 60 min: 659.4 +/- 44.1 ml 100
      ml(-1) min(-1) . s; P = 0.01 and 0.02, respectively, vs before exercise). The
      changes in FBF were due to increased vascular conductance since mean arterial
      blood pressure did not change. In a time control group (N = 5, 34 +/- 3 years,
      three women) that did not exercise, FBF and RH did not change significantly (P =
      0.07 and 0.7, respectively). These results suggest that the increased vascular
      reactivity caused by chronic exercise may result, at least in part, from a
      summation of the subacute effects of successive exercise bouts.

PMID- 15962190
TI  - Effect of aging on carotid artery stiffness and baroreflex sensitivity during
      head-out water immersion in man.
AB  - To examine the possible age-related blood pressure (BP) deregulation in response
      to central hypervolemia, we measured spontaneous baroreflex sensitivity (SBRS),
      carotid arterial compliance (CC), and R-R interval coefficient of variation
      (RRICV) during basal and thermoneutral resting head-out-of-water immersion (HOWI)
      in 7 young (YG = 24.0 +/- 0.8 years) and 6 middle-aged/older (OL = 59.3 +/- 1.3
      years) healthy men. Compared with basal conditions (YG = 19.6 +/- 4.0 vs OL = 6.1
      +/- 1.5 ms/mmHg, P < 0.05), SBRS remained higher in YG than OL during rest HOWI
      (YG = 23.6 +/- 6.6 vs OL = 9.3 +/- 2.1 ms/mmHg, P < 0.05). The RRICV was
      significantly different between groups (YG = 6.5 +/- 1.4 vs OL = 2.8 +/- 0.4%, P
      < 0.05) under HOWI. The OL group had no increase in CC, but a significant
      increase in systolic BP (basal = 115.3 +/- 4.4 vs water = 129.3 +/- 5.3 mmHg, P <
      0.05) under HOWI. In contrast, the YG group had a significant increase in CC
      (basal = 0.16 +/- 0.01 vs water = 0.17 +/- 0.02 mm(2)/mmHg, P < 0.05) with no
      changes in systolic BP. SBRS was positively related to CC (r = 0.58, P < 0.05 for
      basal vs r = 0.62, P < 0.05 for water). Our data suggest that age-related vagal
      dysfunction and reduced CC may be associated with SBRS differences between YG and
      OL groups, and with BP elevation during HOWI in healthy older men.

PMID- 15962191
TI  - Heart rate variability in athletes and nonathletes at rest and during head-up
      tilt.
AB  - The purpose of the present study was to determine if autonomic heart rate
      modulation, indicated by heart rate variability (HRV), differs during supine rest
      and head-up tilt (HUT) when sedentary and endurance-trained cyclists are
      compared. Eleven sedentary young men (S) and 10 trained cyclists (C) were
      studied. The volunteers were submitted to a dynamic ECG Holter to calculate HRV
      at rest and during a 70 masculine HUT. The major aerobic capacity of athletes was
      expressed by higher values of VO2 at anaerobic threshold and peak conditions (P <
      0.05). At rest the athletes had lower heart rates (P < 0.05) and higher values in
      the time domain of HRV compared with controls (SD of normal RR interval, SDNN,
      medians): 59.1 ms (S) vs 89.9 ms (C), P < 0.05. During tilt athletes also had
      higher values in the time domain of HRV compared with controls (SDNN, medians):
      55.7 ms (S) vs 69.7 ms (C), P < 0.05. No differences in power spectral components
      of HRV at rest or during HUT were detected between groups. Based on the analysis
      of data by the frequency domain method, we conclude that in athletes the resting
      bradycardia seems to be much more related to changes in intrinsic mechanisms than
      to modifications in autonomic control. Also, HUT caused comparable changes in
      sympathetic and parasympathetic modulation of the sinus node in both groups.

PMID- 15962192
TI  - Carcinosarcoma of the urinary bladder: a case report.
AB  - Carcinosarcomas are rare tumours containing both malignant mesenchymal and
      epithelial elements. This reports presents a 70-year-old man with carcinosarcoma
      of the urinary bladder, which is proven histologically.

PMID- 15962193
TI  - Use of the appendix as ureteral substitute in a patient with a single kidney
      affected by relapsing upper urinary tract carcinoma.
AB  - The treatment of upper urinary tract transitional cell carcinoma (UT-TCC) in
      single-kidney patients requires the radical removal of cancer, but also, when
      feasible, the preservation of the continuity of the urinary tract by various
      surgical techniques. In case of wide resections during ureteral surgery, a
      ureteral replacement could be advocated. In the literature, the cecal appendix
      has rarely been used as a ureteral substitute, moreover in benign pathological
      conditions, showing encouraging early results. The positive functional and
      oncological outcomes obtained after a lengthy follow-up in a single-kidney
      patient with UT-TCC treated by ureteral resection and appendix interposition
      confirm the viability of this surgical option.

PMID- 15962194
TI  - Clinical holistic medicine: holistic rehabilitation.
AB  - Quality of life, health, and ability are often lost at the same time and most
      often in one decaying existential movement over 5 or 10 years. This "loss of
      life" is mostly too slow to be felt as life threatening, but once awakened to
      reality, it provokes the deepest of fears in patients: the fear of death itself
      and destruction of our mere existence. The horrible experience of having "lost
      life", often without even noticing how it happened, can be turned into a strong
      motivation for improvement. Personal development is about finding the life deeply
      hidden within in order to induce revitalization and rehabilitation.
      Rehabilitation is about philosophy of life with the integration of the repressed
      painful feelings and emotions from the past and the letting go of the associated
      negative beliefs and decisions. The holistic medical toolbox builds on
      existential theories (the quality of life theories, the life mission theory, the
      theory of character, the theory of talent, and the holistic process theory) and
      seems to have the power to rehabilitate the purpose of life, the character of the
      person, and fundamental existential dimensions of man: (1) love; (2) strength of
      mind, feelings, and body; and 3) joy, gender, and sexuality; allowing the person
      once again to express and realize his talents and full potential. The principles
      of rehabilitation are not very different from other healing, but the task is
      often more demanding for the holistic physician as the motivation and resources
      often are very low and the treatment can take many years.

PMID- 15962195
TI  - Clinical holistic medicine: holistic treatment of rape and incest trauma.
AB  - Studies indicate that at least 15% of the female population in western countries
      has experienced sexual abuse and severe sexual traumas. This paper explains how
      even serious sexual abuse and trauma can be healed when care and resources
      encourage the patient to return to the painful life events. When the physician
      cares and receives the trust of the patient, emotional holding and processing
      will follow quite naturally. Spontaneous regression seems to be an almost pain
      free way of integrating the severe traumas from earlier experiences of rape and
      incest. This technique is a recommended alternative to classical timeline therapy
      using therapeutic commands. When traumatized patients distance themselves from
      their soul (feelings, sexuality, and existential depth), they often lose their
      energy and enjoyment of life. However, this does not mean that they are lost to
      life. Although it may seem paradoxical, a severe trauma may be a unique
      opportunity to regain enjoyment of life. The patient will often be richly
      rewarded for the extensive work of clearing and sorting out in order to
      experience a new depth in his or her existence and emotional life, with a new
      ability to understand life in general and other people in particular. So what may
      look like a tragedy can be transformed into a unique gift; if the patient gets
      sufficient support, there is the possibility of healing and learning.
      Consciousness-based medicine seems to provide severely traumatized patients with
      the quality of support and care needed for their soul to heal.

PMID- 15962196
TI  - Case report: a novel solution to penile zipper injury--the needle holder.
AB  - Penile injuries are relatively uncommon. The crush injury mediated by entrapment
      of the skin between the teeth and fastener of a zipper mechanism has been
      described. It is seen more commonly in uncircumcised children than adults. A
      number of treatment methods have been mentioned in the literature. An adult case
      presentation and novel method of management using two small needle holders is
      illustrated.

PMID- 15962197
TI  - Clinical holistic medicine: the existential crisis--life crisis, stress, and
      burnout.
AB  - The triple and parallel loss of quality of life, health, and ability without an
      organic reason is what we normally recognize as a life crisis, stress, or a
      burnout. Not being in control is often a terrible and unexpected experience.
      Failure on the large existential scale is not a part of our expectations, but
      most people will experience it. The key to getting well again is to get resources
      and help, which most people experience with shame and guilt. Stress and burnout
      might seem to be temporary problems that are easily handled, but often the
      problems stay. It is very important for the physician to identify this pattern
      and help the patient to realize the difficulties and seriousness of the
      situation, thus helping the patient to assume responsibility and prevent
      existential disaster, suicide, or severe depression. As soon as the patient is an
      ally in fighting the dark side of life and works with him/herself, the first step
      has been reached. Existential pain is really a message to us indicating that we
      are about to grow and heal. In our view, existential problems are gifts that are
      painful to receive, but wise to accept. Existential problems require skill on the
      part of the holistic physician or therapist in order to help people return to
      life--to their self-esteem, self-confidence, and trust in others. In this paper,
      we describe how we have met the patients soul to soul and guided them through the
      old pains and losses in order to get back on the track to life.

PMID- 15962198
TI  - Clinical holistic medicine: mental disorders in a holistic perspective.
AB  - From a holistic perspective, psychiatric diseases are caused by the patient's
      unwillingness to assume responsibility for his life, existence, and personal
      relations. The loss of responsibility arises from the repression of the
      fundamental existential dimensions of the patients. Repression of love and
      purpose causes depersonalization (i.e., a lack of responsibility for being
      yourself and for the contact with others, loss of direction and purpose in life).
      Repression of strength in mind and emotions leads to derealization (the breakdown
      of the reality testing, often with mental delusions and hallucinations). The
      repression of joy and gender leads to devitalization (emotional emptiness, loss
      of joy, personal energy, sexuality, and pleasure in life). The losses of
      existential dimensions are invariably connected to traumas with life-denying
      decisions. Healing the wounds of the soul by holding and processing will lead to
      the recovery of the person's character, purpose of life, and existential
      responsibility. It can be very difficult to help a psychotic patient. The
      physician must first love his patient unconditionally and then fully understand
      the patient in order to meet and support the patient to initiate the holistic
      process of healing. It takes motivation and willingness to suffer on behalf of
      the patients in order to heal, as the existential and emotional pain of the
      traumas resulting in insanity is often overwhelming. We believe that most
      psychiatric diseases can be alleviated or cured by the loving and caring
      physician who masters the holistic toolbox. Further research is needed to
      document the effect of holistic medicine in psychiatry.

PMID- 15962199
TI  - Clinical holistic medicine: the patient with multiple diseases.
AB  - In clinical practice, patients can present with many different diseases, often
      both somatic and mental. Holistic medicine will try to see the diseases as a
      whole, as symptoms of a more fundamental imbalance in the state of being. The
      holistic physician must help the patient to recover existence and a good
      relationship with self. According to the life mission theory, theory of
      character, and holistic process theory of healing, recovering the purpose of life
      (the life mission) is essential for the patient to regain life, love, and trust
      in order to find happiness and realize the true purpose of life. We illustrate
      the power of the holistic medical approach with a case study of an invalidated
      female artist, aged 42 years, who suffered from multiple severe health problems,
      many of which had been chronic for years. She had a combination of neurological
      disturbances (tinnitus, migraine, minor hallucinations), immunological
      disturbances (recurrent herpes simplex, phlegm in the throat, fungal infection in
      the crotch), hormonal disturbances (14 days of menstruation in each cycle),
      muscle disturbances (neck tensions), mental disturbances (tendency to cry,
      inferiority feeling, mild depression, desolation, anxiety), abdominal complaints,
      hemorrhoids, and more. The treatment was a combined strategy of improving the
      general quality of life, recovering her human character and purpose of life
      ("renewing the patients life energy", "balancing her global information system"),
      and processing the local blockages, thus healing most of her many different
      diseases in a treatment using 30 h of intense holistic therapy over a period of
      18 months.

PMID- 15962202
TI  - Decoding the interactions of SM proteins with SNAREs.
AB  - The success and efficiency of fusion of transport vesicles to target membranes
      depend upon sets of proteins that are functionally and evolutionarily conserved.
      The soluble N-ethylmaleimide-sensitive fusion (NSF)-attachment protein receptor
      (SNARE) family and the Sec1/Munc18 family, also termed SM proteins, are central
      players in this process. SM proteins interact with syntaxins of SNARE family,
      which has been regarded intrinsic for function. By exploring the bi-molecular
      interactions of SM proteins with syntaxins and their functional implications in
      vivo in several eukaryotes, which has been enormously facilitated by the
      availability of the three-dimensional structures of members of both protein
      families, the long-standing assumption that SM proteins fulfill their regulatory
      role by binding to syntaxins has to be reconsidered.

PMID- 15962203
TI  - [Giant cell arteritis].

PMID- 15962204
TI  - [Transcutaneous sonography of the stomach].

PMID- 15962212
TI  - The changing landscape of epidemic bacterial meningitis in Africa: new
      opportunities for prevention.

PMID- 15962213
TI  - An outbreak of serotype 1 Streptococcus pneumoniae meningitis in northern Ghana
      with features that are characteristic of Neisseria meningitidis meningitis
      epidemics.
AB  - BACKGROUND: The Kassena-Nankana District (KND) of northern Ghana lies in the
      African meningitis belt, where epidemics of bacterial meningitis have been
      reoccurring every 8-12 years. These epidemics are generally caused by Neisseria
      meningitidis, an organism that is considered to be uniquely capable of causing
      meningitis epidemics. METHODS: We recruited all patients with suspected
      meningitis in the KND between 1998 and 2003. Cerebrospinal fluid samples were
      collected and analyzed by standard microbiological techniques. Bacterial isolates
      were subjected to serotyping, multilocus sequence typing (MLST), and antibiotic
      resistance testing. RESULTS: A continual increase in the incidence of
      pneumococcal meningitis was observed from 2000 to 2003. This outbreak exhibited
      strong seasonality, a broad host age range, and clonal dominance, all of which
      are characteristic of meningococcal meningitis epidemics in the African
      meningitis belt. The case-fatality rate for pneumococcal meningitis was 44.4%;
      the majority of pneumococcal isolates were antibiotic sensitive and expressed the
      serotype 1 capsule. MLST revealed that these isolates belonged to a clonal
      complex dominated by sequence type (ST) 217 and its 2 single-locus variants,
      ST303 and ST612. CONCLUSIONS: The S. pneumoniae ST217 clonal complex represents a
      hypervirulent lineage with a high propensity to cause meningitis, and our results
      suggest that this lineage might have the potential to cause an epidemic. Serotype
      1 is not included in the currently licensed pediatric heptavalent pneumococcal
      vaccine. Mass vaccination with a less complex conjugate vaccine that targets
      hypervirulent serotypes should, therefore, be considered.

PMID- 15962214
TI  - Phagocytosis of Salmonella montevideo by human neutrophils: immune adherence
      increases phagocytosis, whereas the bacterial surface determines the route of
      intracellular processing.
AB  - Complement-opsonized particles become immune adherent to complement receptor 1
      (CR1 or CD35) on human erythrocytes, allowing particles to be ingested by
      phagocytes in the liver and the spleen. We investigated the role that immune
      adherence plays in the uptake and killing of Salmonella montevideo by human
      neutrophils. Exposure to serum induced loss of flagella and facilitated immune
      adherence, which was followed by more-efficient phagocytosis and killing,
      compared with that after exposure to serum-opsonized, free bacteria. One
      correlate of bacterial killing is the fusion of phagosomes with lysosomes, which
      can be monitored by Lyso-Tracker or lysosomal-associated membrane protein 2
      colocalization with the intracellular bacteria. At 5 min, phagolysosmal fusion
      was significantly faster for immune-adherent bacteria than for non-immune
      adherent bacteria, but, by 35 min, the difference between the 2 groups was
      minimal. Immune adherence also facilitated the ingestion of antibody complement
      opsonized fluorescent microspheres, but, unlike bacteria, most internalized
      microspheres failed to fuse with lysosomes. However, addition of
      lipopolysaccharide, a Toll-like receptor ligand, to microspheres directed their
      intracellular trafficking, resulting in rapid lysosomal fusion. Thus, immune
      adherence facilitates phagocytosis, but the route of intracellular processing
      depends on the molecular nature of the target and is independent of host
      complement and antibody.

PMID- 15962215
TI  - Dual effects of extracellular adherence protein from Staphylococcus aureus on
      peripheral blood mononuclear cells.
AB  - Extracellular adherence protein (Eap) has been suggested as an important
      virulence factor of Staphylococcus aureus because it enhances bacterial adherence
      and internalization into eukaryotic cells, interference with T cells, and
      neutrophil adherence to endothelial cells. We demonstrate that Eap has dual
      effects on peripheral blood mononuclear cells, depending on its concentration. At
      low concentrations (up to 9 microg/mL), Eap induces a proliferative response; at
      higher concentrations, it causes a significant inhibition of T cell proliferation
      induced by S. aureus supernatants toxic shock syndrome toxin-1 or
      phytohemagglutinin. A marked increase in apoptotic (i.e., Annexin V and propidium
      iodide positive) T and B cells could be demonstrated after exposure to the
      inhibitory concentration of Eap. Human anti-Eap antibodies prepared from
      polyspecific immunoglobulin G (IgG) blocked the immunomodulatory effects of Eap.
      Our results demonstrate novel immunomodulatory activities of Eap and identify
      potential mechanisms of action of intravenous IgG therapy in the treatment of S.
      aureus infections.

PMID- 15962216
TI  - Protective anti-V antibodies inhibit Pseudomonas and Yersinia translocon assembly
      within host membranes.
AB  - Pathogenic Yersinia species and Pseudomonas aeruginosa share a similar type III
      secretion/translocation system. The translocation system consists of 3 secreted
      proteins, YopB/PopB, YopD/PopD, and LcrV/PcrV; the latter is known to be a
      protective antigen. In an in vitro assay, the translocation system causes the
      lysis of erythrocytes infected with wild-type (wt) P. aeruginosa. wt Y.
      enterocolitica is not hemolytic, but a multiknockout mutant deprived of all the
      effectors and of YopN ( Delta HOPEMN) is hemolytic. In the presence of antibodies
      against PcrV and Y. pestis LcrV, the hemolytic activity of P. aeruginosa was
      inhibited. Similarly, the hemolytic activity of Delta HOPEMN was inhibited in the
      presence of anti-LcrV antibodies. The assembly of the translocon, composed of
      PopB/D and YopB/D proteins, was disturbed in immunoprotected erythrocyte
      membranes, mimicking the phenotypes of V knockout mutants. Thus, protective
      antibodies against the V antigens of Yersinia species and P. aeruginosa act at
      the level of the formation of the translocon pore in membranes of infected host
      cells by blocking the function of LcrV/PcrV. The hemolysis assay could be adapted
      for high-throughput screening of anti-infectious compounds that specifically
      target the type III translocon.

PMID- 15962217
TI  - Effector functions of heparin-binding hemagglutinin-specific CD8+ T lymphocytes
      in latent human tuberculosis.
AB  - BACKGROUND: Most individuals infected with Mycobacterium tuberculosis do not
      develop tuberculosis (TB) and can be regarded as being protected by an
      appropriate immune response to the infection. The characterization of the immune
      responses of individuals with latent TB may thus be helpful in the definition of
      correlates of protection and the development of new vaccine strategies. The
      highly protective antigen heparin-binding hemagglutinin (HBHA) induces strong
      interferon (IFN)- gamma responses during latent, but not active, TB. Because of
      the recently recognized importance of CD8(+) T lymphocytes in anti-TB immunity,
      we characterized the CD8(+) T lymphocyte responses to HBHA in subjects with
      latent TB. RESULTS: HBHA-specific CD8(+) T lymphocytes expressed memory cell
      markers and synthesized HBHA-specific IFN- gamma . They also restricted
      mycobacterial growth and expressed cytotoxicity by a granule-dependent mechanism.
      This activity was associated with the intracellular expression of HBHA-induced
      perforin. Surprisingly, the perforin-producing CD8(+) T lymphocytes were distinct
      from the IFN- gamma -producing CD8(+) T lymphocytes. CONCLUSION: During latent
      TB, the HBHA-specific CD8(+) T lymphocyte population expresses all 3 effector
      functions associated with CD8(+) T lymphocyte-mediated protective immune
      mechanisms, which supports the notion that HBHA may be protective in humans and
      suggests that markers of HBHA-specific CD8(+) T lymphocyte responses may be
      useful in the monitoring of protection.

PMID- 15962218
TI  - Multinational impact of the 1968 Hong Kong influenza pandemic: evidence for a
      smoldering pandemic.
AB  - BACKGROUND: The first pandemic season of A/H3N2 influenza virus (1968/1969)
      resulted in significant mortality in the United States, but it was the second
      pandemic season of A/H3N2 influenza virus (1969/1970) that caused the majority of
      deaths in England. We further explored the global pattern of mortality caused by
      the pandemic during this period. METHODS: We estimated the influenza-related
      excess mortality in 6 countries (United States, Canada, England and Wales,
      France, Japan, and Australia) using national vital statistics by age for 1967
      1978. Geographical and temporal pandemic patterns in mortality were compared with
      the genetic drift of the influenza viruses by analyzing hemagglutinin and
      neuraminidase sequences from GenBank. RESULTS: In North America, the majority of
      influenza-related deaths in 1968/1969 and 1969/1970 occurred during the first
      pandemic season (United States, 70%; Canada, 54%). Conversely, in Europe and
      Asia, the pattern was reversed: 70% of deaths occurred during the second pandemic
      season. The second pandemic season coincided with a drift in the neuraminidase
      antigen. CONCLUSION: We found a consistent pattern of mortality being delayed
      until the second pandemic season of A/H3N2 circulation in Europe and Asia. We
      hypothesize that this phenomenon may be explained by higher preexisting
      neuraminidase immunity (from the A/H2N2 era) in Europe and Asia than in North
      America, combined with a subsequent drift in the neuraminidase antigen during
      1969/1970.

PMID- 15962219
TI  - Influenza virus neuraminidase contributes to secondary bacterial pneumonia.
AB  - Secondary bacterial pneumonia is a common cause of death during influenza
      epidemics. We hypothesized that virus-specific factors could contribute to
      differences in annual excess mortality. Recombinant influenza viruses with
      neuraminidases from representative strains from the past 50 years were created
      and characterized. The specific level of their neuraminidase activity correlated
      with their ability to support secondary bacterial pneumonia. Recombinant viruses
      with neuraminidases from 1957 and 1997 influenza strains had the highest level of
      activity, whereas a virus with the neuraminidase from a 1968 strain had the
      lowest level of activity. The high level of activity of the neuraminidase from
      the 1957 strain, compared with that of other neuraminidases, more strongly
      supported the adherence of Streptococcus pneumoniae and the development of
      secondary bacterial pneumonia in a mouse model. These data lend support to our
      hypothesis that the influenza virus neuraminidase contributes to secondary
      bacterial pneumonia and subsequent excess mortality.

PMID- 15962220
TI  - Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear
      cells from HCV-monoinfected and HIV/HCV-coinfected persons.
AB  - It has been speculated that hepatitis C virus (HCV) replicates in peripheral
      blood mononuclear cells (PBMCs), which, therefore, may be a site for interaction
      with human immunodeficiency virus (HIV). We used strand-specific real-time
      polymerase chain reaction to detect HCV RNA in 28 HCV-monoinfected and 20 HIV/HCV
      coinfected women. At the first visit, positive-strand HCV RNA was detected in
      serum samples from 89% of the women, whereas positive-strand HCV RNA was detected
      in PBMC samples from 32% and 55% of the HCV-monoinfected and HIV/HCV-coinfected
      women, respectively. After initiation of antiretroviral therapy, the HIV/HCV
      coinfected women were significantly more likely to have detectable positive- and
      negative-strand HCV RNA in the PBMC compartment than were the HCV-monoinfected
      women. HIV and HCV RNA levels were not correlated. Serum HCV RNA levels were
      correlated over time; HCV RNA levels in the serum and PBMC compartments were not.
      These data suggest differential regulation of HCV RNA in the serum and PBMC
      compartments and may partially explain the limited HCV antiviral response rates
      observed in coinfected persons.

PMID- 15962221
TI  - Hepatitis C virus core protein and hepatitis activity are associated through
      transactivation of interleukin-8.
AB  - BACKGROUND: We evaluated the association between variations in hepatitis C virus
      (HCV) core protein and hepatitis severity in patients with chronic HCV infection
      who achieved remission without viral eradication and had a biochemical response
      to interferon (IFN) therapy, to evaluate the effect of HCV core sequence in the
      absence of the influence of host factors. METHODS. Using serum from 10 patients
      with a biochemical response and 10 patients with no response, we measured serum
      levels of interleukin (IL)-1 beta , IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IFN-
      gamma , and tumor necrosis factor- alpha before and after IFN therapy. Expression
      vectors with the core region were transfected into Huh7 cells, and cytokine
      induction was evaluated by reporter assay. RESULTS: In biochemical responders,
      only IL-8 levels decreased after IFN therapy (P=.04). Changes in the C-terminal
      hydrophobic region were observed more frequently in biochemical responders.
      Activation of the IL-8 promoter by HCV core protein was significantly decreased
      in biochemical responders after IFN therapy (P=.04). When 69 C-terminal amino
      acids from before IFN therapy were replaced with those from after IFN therapy in
      3 biochemical responders, their ability to transactivate IL-8 decreased.
      CONCLUSIONS: Differences in amino acids in the HCV core protein correlates with
      hepatitis activity through the modulation of IL-8 induction in HCV-infected
      patients.

PMID- 15962222
TI  - Single-nucleotide polymorphisms associated with symptomatic infection and
      differential human gene expression in healthy seropositive persons each implicate
      the cytoskeleton, integrin signaling, and oncosuppression in the pathogenesis of
      human parvovirus B19 infection.
AB  - This study was undertaken to further examine the role of the host response to
      parvovirus B19 in the development of symptoms and consequences of viral
      persistence. Genomic DNA from 42 patients with symptomatic B19 infection was
      analyzed using the HuSNP assay (Affymetrix), and the results were compared with
      those from analysis of 53 healthy control individuals. Fifty-seven single
      nucleotide polymorphisms were identified that were significantly associated with
      symptomatic infection. Total RNA from peripheral blood mononuclear cells from 57
      B19-seropositive and 13 B19-seronegative donors was analyzed by hybridization to
      a single-color microarray representing 9522 human genes. Ninety-two genes were
      shown to be differentially expressed. Differential expression was confirmed in 6
      of 38 genes (SKIP, MACF1, SPAG7, FLOT1, c6orf48, and RASSF5) tested using real
      time quantitative polymerase chain reaction in a different group of healthy
      subjects. Genes identified in both studies play a functional role in the
      cytoskeleton, integrin signaling, and oncosuppression, themes that have been
      shown to be important in parvovirus infections.

PMID- 15962223
TI  - Persistent West Nile virus infection in the golden hamster: studies on its
      mechanism and possible implications for other flavivirus infections.
AB  - Golden hamsters (Mesocricetus auratus) experimentally infected with West Nile
      virus (WNV) developed chronic renal infection and persistent shedding of virus in
      urine for up to 8 months, despite initial rapid clearance of virus from blood and
      the timely appearance of high levels of specific neutralizing antibodies.
      Infectious WNV could be recovered by direct culture of their urine and by
      cocultivation of kidney tissue for up to 247 days after initial infection. Only
      moderate histopathologic changes were observed in the kidneys or brain of the
      chronically infected hamsters, although WNV antigen was readily detected by
      immunohistochemistry within epithelium, interstitial cells, and macrophages in
      the distal renal tubules. Comparison of WNV isolates from serial urine samples
      from individual hamsters over several months indicated that the virus underwent
      both genetic and phenotypic changes during persistent infection. These findings
      are similar to previous reports of persistent infection with tickborne
      encephalitis and Modoc viruses.

PMID- 15962225
TI  - Type I interferon production is profoundly and transiently impaired in primary
      HIV-1 infection.
AB  - BACKGROUND: Successful immunological control of human immunodeficiency virus
      (HIV) infection is achieved only in rare individuals. Plasmacytoid dendritic
      cells (DCs) are mostly responsible for the production of strong antiviral factors
      -that is, type I interferons (IFNs)--in response to viruses. Their natural IFN
      production is impaired in chronic HIV infection, in correlation with viral load
      and disease progression, but it has not been tested during the critical stage of
      primary infection, when a balance is set between host immune responses and viral
      replication. METHODS: We longitudinally studied 26 patients during the primary
      stage of HIV infection. Fifteen patients received highly active antiretroviral
      therapy (HAART) for 12 months. RESULTS: At the time of inclusion into the cohort,
      median type I IFN production in response to herpes simplex virus type 1
      stimulation was dramatically impaired in peripheral blood mononuclear cells
      (PBMCs) from HIV-infected patients, compared with that in PBMCs from 31
      uninfected donors (180 vs. 800 IU/mL; P<.0001). Median circulating plasmacytoid
      DC counts were also significantly decreased (7300 vs. 13,500 cells/mL; P=.001).
      Twelve months later, IFN production returned to normal, and the data suggest that
      HAART may help in the recovery of IFN production by plasmacytoid DCs.
      CONCLUSIONS: These data underline the potential for early antiretroviral
      treatment and IFN- alpha treatment to enhance viral control in a larger
      proportion of patients during the critical stage of primary infection.

PMID- 15962224
TI  - Immune reconstitution after receipt of highly active antiretroviral therapy in
      children with advanced or progressive HIV disease and complete or partial viral
      load response.
AB  - We assessed CD4 cell recovery in 175 children with advanced human
      immunodeficiency virus disease who had received a 4-drug antiretroviral regimen
      and were categorized as viral load (VL) responders (VLRs), partial VLRs, or non
      VLRs. Median CD4 cell counts increased from baseline to week 48, and, among
      children with maximal follow-up, increases in CD4 cell counts were sustained to
      week 96 among VLRs and partial VLRs but not among non-VLRs. For VL rebounders
      still in the study, CD4 cell counts remained increased for 32 weeks after VL
      rebound. Sustained immunologic benefits can be achieved even with partial VL
      response in children with advanced disease.

PMID- 15962226
TI  - The effect of micronutrient supplementation on disease progression and death in
      simian immunodeficiency virus-infected juvenile male rhesus macaques.
AB  - BACKGROUND: We investigated the impact that micronutrient supplementation has on
      the progression of simian acquired immunodeficiency syndrome (SAIDS). METHODS:
      Twenty-four simian immunodeficiency virus-infected juvenile male rhesus macaques
      were randomized into 2 groups. One group was given certified chow, and the other
      group was given chow and a supplement that contained 2-3 times the estimated
      nutritional requirement of micronutrients. Virological, immunological, and body
      composition measurements were taken every 4 weeks for 120 weeks. RESULTS: There
      was no difference between groups in weight gain, body mass index (BMI), crown
      heel length, waist circumference, total tissue mass, lean mass, bone mineral
      content, or bone mineral density. The rhesus macaques on the supplemented diet
      had a higher death rate (hazard ratio, 2.39; P<.001) than those on the
      nonsupplemented diet; death in both groups was associated with a higher viral
      load set point during the early phase of infection. Additionally, higher body
      weight, BMI, crown-rump length, and lower viral load set point were protective
      from death in both groups. CONCLUSIONS: Micronutrient supplementation did not
      significantly alter the progression of SAIDS with respect to changes in body
      composition and immunological characteristics. A significantly higher rate of
      death was observed in rhesus macaques on the supplemented diet.

PMID- 15962227
TI  - Efficacy of DB289 in Thai patients with Plasmodium vivax or acute, uncomplicated
      Plasmodium falciparum infections.
AB  - BACKGROUND: DB289 is the orally active prodrug of the diamidine DB75, which was
      developed for the treatment of human African trypanosomiasis. METHODS: We tested
      the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute,
      uncomplicated P. falciparum infections in an open-label pilot study at the
      Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections
      and 23 patients with P. falciparum infections were admitted and treated with 100
      mg of DB289 given orally twice a day for 5 days and were followed for 28 days.
      Patients with P. vivax infections were also treated with primaquine on days 10
      23. RESULTS: All patients cleared parasites by day 7, with a mean+/-SD clearance
      time of 43+/-41 h. One patient with a P. vivax infection had a recurrence of
      parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had
      recurrences of parasitemia caused by P. vivax and 2 had recurrences of
      parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia
      caused by P. falciparum were the parasites genotypically distinct from the
      infecting parasites the patient had at enrollment, which means there was a 96%
      cure rate. CONCLUSIONS: DB289 is a promising new antimalarial compound that could
      become an important component of new antimalarial combinations.

PMID- 15962228
TI  - White blood cell counts and malaria.
AB  - White blood cells (WBCs) were counted in 4697 individuals who presented to
      outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru,
      between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each
      site and in each year, WBC counts in the Plasmodium falciparum-infected patients
      were lower than those in the Plasmodium vivax-infected patients, which, in turn,
      were lower than those in the uninfected patients. In Thailand, one-sixth of the
      P. falciparum-infected patients had WBC counts of <4000 cells/microL. Leukopenia
      may confound population studies that estimate parasite densities on the basis of
      an assumed WBC count of 8000 cells/microL. For instance, in the present study,
      use of this conventional approach would have overestimated average asexual
      parasite densities in the P. falciparum-infected patients in Thailand by nearly
      one-third.

PMID- 15962229
TI  - High level of var2csa transcription by Plasmodium falciparum isolated from the
      placenta.
AB  - Plasmodium falciparum parasites that bind to chondroitin sulphate A (CSA) express
      unique variant surface antigens that are involved in the placental sequestration
      that precipitates pregnancy-associated malaria (PAM). Two var gene subfamilies,
      var1csa and var2csa, have been associated with CSA binding. We show here that
      placental P. falciparum isolates highly transcribed var2csa but not var1csa.
      var2csa was not transcribed or was only minimally transcribed by parasites
      isolated from nonpregnant women. Placental parasites that effectively bound to
      placental chondroitin sulphate proteoglycans transcribed higher levels of
      var2csa. In pregnant women, levels of var2csa transcription and plasma anti
      VAR2CSA immunoglobulin G were associated. These findings support the idea that
      VAR2CSA plays a crucial role in PAM and strengthen the rationale for the
      development of VAR2CSA-based vaccines.

PMID- 15962230
TI  - Mice with disseminated candidiasis die of progressive sepsis.
AB  - BACKGROUND: Candida species are among the most common etiologies of nosocomial
      bloodstream infections, causing a mortality of >40%. The murine model of
      hematogenously disseminated candidiasis is the standard for investigating both
      the activity of antifungal agents and the pathogenesis of this disease. However,
      despite decades of use, little is known about the physiological characteristics
      of the host in this model, and the cause of death remains unclear. METHODS: Using
      i-STAT technology, we measured blood chemistry and hemodynamic parameters to
      define host physiological characteristics during murine disseminated candidiasis.
      RESULTS: Mice with hematogenously disseminated candidiasis died of progressive
      sepsis, as manifested by worsening hypotension, tachycardia, and hypothermia. The
      mice developed metabolic acidosis, as well as profound acidemia and hypoglycemia.
      They also developed renal insufficiency, which became severe only shortly before
      death. Kidney fungal burden was correlated with severity of renal failure and
      systemic acidosis. The presence of significant weight loss, hypotension, or
      hypothermia was predictive of imminent death. CONCLUSIONS: These findings
      indicate that the murine model of hematogenously disseminated candidiasis
      accurately recapitulates the progressive sepsis seen during severe clinical
      cases. The results underscore the validity of the model for study of the
      pathophysiological aspects of this disease, as well as for the evaluation of
      antifungal drug efficacy.

PMID- 15962231
TI  - Genetic variations in the receptor-ligand pair CCR5 and CCL3L1 are important
      determinants of susceptibility to Kawasaki disease.
AB  - Kawasaki disease (KD) is an enigmatic, self-limited vasculitis of childhood that
      is complicated by development of coronary-artery aneurysms. The high incidence of
      KD in Asian versus European populations prompted a search for genetic
      polymorphisms that are differentially distributed among these populations and
      that influence KD susceptibility. Here, we demonstrate a striking, inverse
      relationship between the worldwide distribution of CCR5- Delta 32 allele and the
      incidence of KD. In 164 KD patient-parent trios, 4 CCR5 haplotypes including the
      CCR5- Delta 32 allele were differentially transmitted from heterozygous parents
      to affected children. However, the magnitude of the reduced risk of KD associated
      with the CCR5- Delta 32 allele and certain CCR5 haplotypes was significantly
      greater in individuals who also possessed a high copy number of the gene encoding
      CCL3L1, the most potent CCR5 ligand. These findings, derived from the largest
      genetic study of any systemic vasculitis, suggest a central role of CCR5-CCL3L1
      gene-gene interactions in KD susceptibility and the importance of gene modifiers
      in infectious diseases.

PMID- 15962232
TI  - Questions concerning the New Haven coronavirus.

PMID- 15962233
TI  - Lack of association between New Haven coronavirus and Kawasaki disease.

PMID- 15962234
TI  - Kawasaki disease and human coronavirus.

PMID- 15962238
TI  - Insulin-transferrin-selenium prevent human chondrocyte dedifferentiation and
      promote the formation of high quality tissue engineered human hyaline cartilage.
AB  - This study was to investigate the effects of insulin-transferrin-selenium (ITS)
      on the proliferation and quantitative gene expression of adult human nasal septum
      chondrocytes in monolayer culture expansion and the formation of tissue
      engineered hyaline cartilage. Effects of ITS on human nasal septum chondrocytes
      monolayer culture expansion and gene expression were evaluated in various culture
      media either added with 2% fetal bovine serum (FBS) or 1 ng/mL basic fibroblast
      growth factor plus 1 ng/mL transforming growth factor or both serum and growth
      factors supplementation in comparison with medium added with 10%FBS. Chondrocytes
      cultured in medium added with 2% fetal bovine serum and growth factors either
      supplemented with or without ITS were then mixed with pluronic F-127 hydrogel for
      in vivo tissue engineered cartilage formation in nude mice model. Engineered
      tissues were removed after 8 weeks of implantation and evaluated with
      histological staining, immunohistochemistry, transmission electron microscopy and
      quantitative gene expression analysis. ITS promoted human chondrocytes
      proliferation and reduced chondrocytes dedifferentiation in media supplemented
      with serum and growth factors. ITS with 2% FBS and growth factors provided 15
      fold increased in chondrocytes number by the end of the culture period compared
      to the standard culture medium used in chondrocytes culture (medium added with
      10% FBS). Engineered tissue resulted from ITS supplementation demonstrated higher
      quality of cartilage formation. In conclusion, our study has demonstrated the
      benefits of ITS supplementation in human chondrocytes monolayer culture and
      tissue engineering cartilage formation.

PMID- 15962239
TI  - Mental models and meaningful learning.
AB  - If you understand something, you can use the information you have acquired to
      solve problems to which that knowledge is relevant. Meaningful learning is
      learning with understanding. Achieving meaningful learning begins with the
      building of correct, appropriate mental models, or representations, of the
      knowledge being acquired. The next step is learning to use the available mental
      models to solve problems. In many of the biomedical sciences, this means being
      able to either calculate something, predict the responses of the system, or
      explain the responses of the system. Since only the learner can do the learning,
      the only possible role for the teacher is to help the learner to learn. This
      means creating an active learning environment in which the learner can acquire
      the needed information, continually test the mental models being built, and
      correct or refine those models as needed. In an active learning environment,
      students are given ample opportunities to learn to solve problems. If the goal of
      the course is the achievement of meaningful learning, it is essential that the
      students then be assessed to determined whether they have reached that goal.

PMID- 15962237
TI  - Deletions involving long-range conserved nongenic sequences upstream and
      downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis
      syndrome.
AB  - The expression of a gene requires not only a normal coding sequence but also
      intact regulatory regions, which can be located at large distances from the
      target genes, as demonstrated for an increasing number of developmental genes. In
      previous mutation studies of the role of FOXL2 in blepharophimosis syndrome
      (BPES), we identified intragenic mutations in 70% of our patients. Three
      translocation breakpoints upstream of FOXL2 in patients with BPES suggested a
      position effect. Here, we identified novel microdeletions outside of FOXL2 in
      cases of sporadic and familial BPES. Specifically, four rearrangements, with an
      overlap of 126 kb, are located 230 kb upstream of FOXL2, telomeric to the
      reported translocation breakpoints. Moreover, the shortest region of deletion
      overlap (SRO) contains several conserved nongenic sequences (CNGs) harboring
      putative transcription-factor binding sites and representing potential long-range
      cis-regulatory elements. Interestingly, the human region orthologous to the 12-kb
      sequence deleted in the polled intersex syndrome in goat, which is an animal
      model for BPES, is contained in this SRO, providing evidence of human-goat
      conservation of FOXL2 expression and of the mutational mechanism. Surprisingly,
      in a fifth family with BPES, one rearrangement was found downstream of FOXL2. In
      addition, we report nine novel rearrangements encompassing FOXL2 that range from
      partial gene deletions to submicroscopic deletions. Overall, genomic
      rearrangements encompassing or outside of FOXL2 account for 16% of all molecular
      defects found in our families with BPES. In summary, this is the first report of
      extragenic deletions in BPES, providing further evidence of potential long-range
      cis-regulatory elements regulating FOXL2 expression. It contributes to the
      enlarging group of developmental diseases caused by defective distant regulation
      of gene expression. Finally, we demonstrate that CNGs are candidate regions for
      genomic rearrangements in developmental genes.

PMID- 15962240
TI  - The building blocks in the professional education process that lead to best
      practices and quality medicine.
AB  - It is time for the faculty of veterinary colleges to take responsibility for the
      veterinary curriculum, to move beyond the debate over teaching styles, and to
      understanding what a curriculum needs to accomplish. Our challenge is to engage
      students, faculty, and all veterinary professionals in evidence-based medicine
      and medical outcomes assessment and to identify best practices and continually
      improve the quality of veterinary health care. The education program of students
      must lay the foundation for this essential approach to veterinary practice.

PMID- 15962241
TI  - Global perspectives of veterinary education: reflections from the 27th World
      Veterinary Congress.
AB  - All who work in veterinary education must recognize the breadth of their
      responsibilities. We are at a time in veterinary history where the profession
      must look how to meet a global standard for veterinary education and the global
      recognition of our basic qualification. There is a societal expectation that a
      professional approach is being taken to managing food security and food safety,
      as well as the environment and biodiversity. Within our profession, we need to
      recognize our obligation to fulfill this role. Society and regulators will seek
      those who have the capacity to provide for society's needs. It is no longer a
      case of relying on the reputation of our profession alone. There is a significant
      disparity in universal recognition of the veterinary qualification between the
      major blocs of the developed world and the developing world. Graduates from
      developing countries are not widely recognized, and they and their countries may
      therefore be at a significant disadvantage. There will be significant costs
      involved in raising the standards of veterinary education. A lead must be taken
      by a global body such as the World Veterinary Association to develop a long-term
      strategy toward global recognition of the veterinary qualification.

PMID- 15962242
TI  - Standards of veterinary education for the future: preparing the profession for
      the new century.

PMID- 15962243
TI  - Veterinary education in a global village.

PMID- 15962244
TI  - The needs for public health education: reflections from the 27th world veterinary
      congress.
AB  - The needs for public health education are addressed based on papers presented at
      the 27th World veterinary Congress held in Tunis, Tunisia, on September 25-29,
      2002. The article first summarizes the public health problems presented from
      developing countries, followed by the problems from developed countries. A
      summary of the solutions proposed or practiced by each group of speakers is
      presented. On the basis of the problems and solutions presented, the author
      suggests how education can address the problems and their solutions. The
      dichotomy between developed and developing countries is not new, but educational
      advances in veterinary public health (VPH) are required to provide the citizens
      of all countries with safe food and less risk of zoonotic diseases. This is true
      whether a country is too poor to have adequate veterinary services for good food
      safety and preventing major zoonoses, or is a wealthy country plagued by the
      emerging pathogens associated with modern intensive agriculture systems.

PMID- 15962245
TI  - Veterinarians with disabilities: an international issue.

PMID- 15962246
TI  - Veterinary education in Brazil: past history, current issues.

PMID- 15962247
TI  - Needs, difficulties, and possible approaches to providing quality clinical
      veterinary education with the aim of improving standards of companion animal
      medicine in sri lanka.
AB  - Companion animal medicine has now gained prominence in Sri Lanka as a result of
      an increased public interest in pets; however, veterinary education has not kept
      pace with current developments. The main constraints faced by the veterinary
      education system are those common to all university education in Sri Lanka.
      Changes in the current system, though important, depend heavily on political will
      and vision, which are not forthcoming in the near future. It is therefore both
      necessary and important that the private sector provide the impetus to improve
      standards of veterinary medicine in Sri Lanka. The immediate focus should be on
      improving the skills of practitioners through clinically based continuing
      education programs. Later, more specialized and intensive programs may be
      initiated. Interaction and sharing of knowledge with more developed countries are
      critical in leading the way to improved standards of companion animal medicine in
      Sri Lanka.

PMID- 15962248
TI  - Reflections upon the trends of education and research in small animal
      reproduction in Europe.
AB  - An open questionnaire-based survey was performed among 86 institutions of
      veterinary education in 32 European countries: 15 within the European Union (EU)
      and 17 outside the EU, in Central and Eastern Europe and the European Free Trade
      Association (EFTA). The survey aimed to provide a view of the general status of
      education and research in small animal reproduction (SAR) in Europe. It further
      aimed to disclose whether ongoing trends in organization (e.g., from the
      classical animal reproduction discipline orientation [DO] toward a species
      oriented [SO] organization) among veterinary colleges responsible for
      undergraduate education and research in SAR have affected the provision of
      clinical services, continuing professional development (CPD), specialization,
      post-graduate education, and research. Response rates reached 80% among EU
      institutions and 48.4% in other countries (overall response rate = 68.6%). A
      clear, significant majority of institutions (> 60%) were DO, with a well-defined
      comparative subject in the veterinary curriculum. No differences were reported
      for either orientation in their ability to provide undergraduate education or
      clinical services in SAR. However, more DO institutions reported active research
      in SAR than their SO counterparts. Similar (and stronger) differences were seen
      for post-graduate education, CPD, and participation in specialization programs
      (national or European). Finally, more DO than SO institutions provided assisted
      reproductive technologies (ARTs), such as AI with frozen semen, to customers. The
      analysis of the data emanating from the respondents' perceptions, supports the
      advantages of the more classical, DO-based approach. The results highlight the
      need for caution when institutions abandon the comparative benefits of the
      classical DO animal reproduction subject for a SO approach, which tends to
      prioritize clinical specialized service rather than research and research
      education. In the author's opinion, in the absence of the data generated by
      comparative research and used in research education and the development of new
      technologies in SAR, there is a risk that sound science-based academic
      preparation for undergraduates and candidates for post-graduate research
      education is constrained. To counteract these negative trends, SAR must be
      recognized as a very important branch of the department of animal reproduction.
      Access to resources, personnel for teaching and research, and curriculum space
      should be made available in order to provide the basis for relevant post-graduate
      training, specialization, and research.

PMID- 15962249
TI  - Informative evaluation of the teaching skills of the faculty at Alfort veterinary
      school.
AB  - A quantitative method for the informative evaluation of teaching activities was
      devised using a survey from 33 experts. It is based on an evaluation, by students
      and two peers, of the four steps of the instructional methodology: analysis of
      training needs, statement of learning objectives, delivery of teaching session,
      and testing of student performance. Faculty evaluation is optional, and results
      are strictly confidential. Results of a three-year trial of this protocol at the
      Alfort veterinary school are presented and discussed. Each year the method has
      been assessed and some changes have been implemented. It is now felt that
      evaluation questionnaires for lectures and tutorial sessions have been validated,
      while those for laboratories and clinical teaching have to be tested through a
      larger number of settings. A the same time, a change from informative to
      summative evaluation is under consideration.

PMID- 15962250
TI  - The history of veterinary education in India.

PMID- 15962251
TI  - Ensuring that the competent are truly competent: an overview of common methods
      and procedures used to set standards on high-stakes examinations.
AB  - Determining whether or not an examinee has met an adequate standard of
      performance constitutes a central task for licensure and certification bodies.
      Consequently, standard setting is a key activity for all certification and
      licensing testing programs. The purpose of this article is to provide an overview
      of methods that have been proposed for set a passing standard on an examination.
      First, the distinction between norm-referenced and criterion-referenced methods
      for setting a standard will be outlined. Then, both test-centered and examinee
      centered methods for setting a passing standard will be explicated. The
      importance of factoring in the consequences of adopting a standard will also be
      illustrated via the Hofstee method. In the concluding section, important issues
      pertaining to the selection of panelists as well as the validation of the
      standard will be addressed briefly.

PMID- 15962252
TI  - Professional and veterinary competencies: addressing human relations and the
      human-animal bond in veterinary medicine.
AB  - PURPOSE: The purpose of this study was to determine the nature and degree of
      coverage of human relations and the human-animal bond in veterinary curricula
      across North America. The attitudes and opinions of a cohort of veterinary
      students and alumni about human relations skills and human-animal bond training
      in the veterinary program was also investigated. METHOD: Twenty veterinary
      schools across North America were contacted and data were collected regarding
      their coverage of human relations and the human-animal bond in the curriculum. A
      survey was developed to measure attitudes and opinions about this type of
      training. The survey was disseminated to students in years 1 to 4 and alumni from
      the Ontario Veterinary College (OVC). Data were analyzed descriptively. RESULTS:
      Based on availability of contact people, 20 schools in North America were
      contacted, and all participated in the study. Each of the veterinary schools
      surveyed has incorporated strategies for teaching human relations skills through
      required courses, electives, guest speakers, and/or community service programs.
      The overall participation rate for OVC students was 53%. Ninety-nine percent of
      all students surveyed agreed that their ability to deal with people using
      effective human relations skills was a concern, and all students said they would
      like to receive more training in this area. There was a 41% participation rate
      for OVC alumni. Fifty-five percent of alumni said they had learned enough in the
      veterinary program to employ effective human relations skills in practice, yet
      65% felt they had not received enough instruction in addressing the human-animal
      bond specifically. CONCLUSIONS: It is apparent that veterinary schools recognize
      the need to prepare entry-level practitioners to deal with the human-animal bond
      and with human relations. It is also evident that students and practitioners
      value receiving information of this nature in the curriculum and desire further
      training. Specific learning objectives for veterinary curricula have been
      outlined based on findings from this study.

PMID- 15962253
TI  - A model euthanasia workshop: one class's experience at Tufts University.
AB  - Performing euthanasia is likely one of the most challenging tasks a veterinarian
      faces. Four students at Tufts University School of Veterinary Medicine felt that
      they and their classmates needed additional training on this subject. They
      informally surveyed their classmates to determine what topics and formats the
      students desired. The findings were used to develop the Euthanasia Workshop at
      the university, a voluntary series of lectures and discussions on technical and
      emotional issues relating to euthanasia. The four students then informally
      surveyed 30 North American veterinary colleges to determine the scope of
      euthanasia training in other veterinary programs. They found that euthanasia,
      while often covered within other courses, is rarely taught as a stand-alone
      course.

PMID- 15962254
TI  - Attitudes of veterinary medical students and medical students toward
      collaborative learning: an experiment.
AB  - This study measured the attitudes of 55 medical students and 30 veterinary
      medical students as they participated in an experiment of collaborative teaching
      and learning about basic surgical skills. Two parallel forms of an attitude
      questionnaire were developed, with three subscales: confidence in one's own
      surgical skill; collaboration with the other type of student; and inter
      professional collaboration in general. These attitude scales were administered
      before and after an experiment involving the veterinary medical students teaching
      the medical students incision and exploratory laparoscopy in a laboratory setting
      using live rabbits. After the experiment, measures of the medical students'
      attitudes had increased significantly on all three subscales. Measures of the
      veterinary students' attitudes increased significantly on two subscales but
      declined on the subscale of inter-professional collaboration.

PMID- 15962255
TI  - An anatomist's comments on learning and teaching.
AB  - A Texas farm boy, who entered veterinary school in 1966 with the goal of becoming
      a "cow doctor" but instead has ended up teaching anatomy for more than 30 years,
      shares some of his personal philosophy and ideas about learning and teaching. The
      author claims no special expertise in teaching methodology, offers no "cutting
      edge" techniques, and presents no particularly "novel" concepts on how to be a
      good teacher. He merely shares his personal, common-sense teaching philosophy,
      which is pretty much summarized in "Smallwood's 12 or More Axioms of Learning and
      Teaching". As a "parting shot", the author comments briefly on teaching anatomy
      using the problem-based learning approach.

PMID- 15962256
TI  - Tailored therapy for early Barrett's lesions.

PMID- 15962257
TI  - Stapled transanal rectal resection for obstructed defaecation and evidence-based
      practice.

PMID- 15962258
TI  - Surgical management of chronic pain after inguinal hernia repair.
AB  - BACKGROUND: Chronic pain after inguinal hernia repair is an adverse outcome that
      affects about 12 per cent of patients. Principles of treatment have not been
      defined. This review examines neurectomy and mesh or staple removal as possible
      treatments. METHOD: A literature search was carried out using the Medline and
      Ovid databases. Keywords were 'pain; chronic', 'herniorrhaphy; inguinal',
      'neurectomy' and similar words. Article references were cross-checked for
      additional references. Articles were reviewed for data on surgical treatment of
      chronic pain after hernia repair. RESULTS: Neurectomy of the ilioinguinal,
      iliohypogastric, genitofemoral or lateral femoral cutaneous nerve was described
      in 14 papers. Overall, a favourable outcome was reported. However, the
      methodological quality was poor in all studies in respect of preoperative
      diagnostic criteria and treatment, intraoperative success in identifying a
      pathological lesion or nerve and quality of follow-up; this hindered
      interpretation of the data. Insufficient information is available at present on
      the effect of removal of mesh or staples. CONCLUSION: Chronic pain after hernia
      repair is a significant problem and there is a need for a definitive assessment
      of its surgical treatment.

PMID- 15962259
TI  - Risk factors for anastomotic failure after total mesorectal excision of rectal
      cancer (Br J Surg 2005; 92: 211-216).

PMID- 15962260
TI  - Sex-based analysis of the outcome of laparoscopic cholecystectomy for acute
      cholecystitis (Br J Surg 2005; 92: 463-466).

PMID- 15962261
TI  - Ethics of palliative surgery in patients with cancer.
AB  - BACKGROUND: Surgery is an important palliative method for patients with advanced
      malignant disease. In addition to concerns related to clinical decision making,
      various moral challenges are encountered in palliative surgery. Some of these
      relate to the patients and their illness, others to the surgeons, their
      attitudes, skills and knowledge base. METHOD AND RESULTS: Pertinent moral
      challenges are addressed and analysed with respect to prevailing perspectives in
      normative ethics. The vulnerability of patients with non-curable cancer calls for
      moral awareness. Demands regarding sensibility and precaution in this clinical
      setting represent substantial challenges with regard to the 'duty to help',
      benevolence, respect of autonomy and proper patient information. Moreover,
      variations in definition of palliative surgery as well as limited scientific
      evidence with respect to efficacy, effectiveness and efficiency pose
      methodological and moral problems. Therefore, a definition of palliative surgery
      that addresses these issues is provided. CONCLUSION: Both surgical skill and much
      moral sensibility are required to improve palliative care in surgical oncology.
      This should be taken into account not only in clinical practice but also in
      education and research.

PMID- 15962262
TI  - Laparoscopic surgery for colorectal cancer (Br J Surg 2005; 92: 519-520).

PMID- 15962263
TI  - Validity of the Glasgow Aneurysm Score and the Hardman Index in predicting
      outcome after ruptured abdominal aortic aneurysm repair (Br J Surg 2005; 92: 570
      573).

PMID- 15962265
TI  - A novel osteotropic biomaterial OG-PLG: in vitro efficacy.
AB  - Previously, a novel osteotropic biomaterial, OG-PLG [simvastatin grafted to
      poly(lactide-co-glycolide), PLG], was synthesized and shown to have degradation
      controlled release kinetics. The objective here was to determine the effect of
      grafting statins to PLG on bone regeneration in vitro. Rat bone marrow cells were
      stimulated in vitro with simvastatin dissolved in media, saponified simvastatin
      dissolved in media, simvastatin released through diffusion from emulsion freeze
      dried scaffolds, and OG-PLG. Unstimulated cultures and cultures stimulated with
      dexamethasone were used as negative and positive controls, respectively. In vitro
      bone formation was assessed using the alkaline phosphatase (ALP) and von Kossa
      assays at different times up to 16 days. ALP analysis revealed that saponified
      simvastatin at 10(-7)M and OG-PLG significantly increased ALP expression at
      various time points. von Kossa assay showed that simvastatin, saponified
      simvastatin, and OG-PLG significantly enhanced mineralization, with the effect
      from OG-PLG being the most significant. In short, OG-PLG significantly enhanced
      in vitro bone cell mineralization beyond the effect of simvastatin or saponified
      simvastatin dissolved in media and simvastatin released via diffusion from
      scaffolds.

PMID- 15962266
TI  - Role of granulocytes and monocytes in the polyvinyl chloride-induced synthesis of
      interleukin 8, monocyte chemoattractant protein 1, and leukotriene B4.
AB  - In an in vitro whole blood model of artificial surface-induced inflammation, we
      have studied the contribution of leukocyte populations in the synthesis of
      inflammatory mediators. This was done by depleting the blood of specific cell
      types using magnetic beads coated with monoclonal antibodies against leukocyte
      surface antigens. Synthesis of interleukin 8 (IL-8) was highly dependent on CD15+
      cells and was reduced by 80% when these cells were removed from the blood.
      Correspondingly, IL-8 production showed a high correlation with the concentration
      of granulocytes (r = 0.77, p < 0.0001). Synthesis of monocyte chemoattractant
      protein 1 (MCP-1) was dependent on CD14+ cells and was reduced by 35% when these
      cells were removed from the blood. Correspondingly, MCP-1 production correlated
      with the concentration of monocytes (r = 0.39, p < 0.0001). Synthesis of
      leukotriene B4 (LTB4) was highly dependent on CD15+ cells and was reduced by 75%
      when these cells were removed from the blood. Correspondingly, LTB4 production
      correlated strongly with the granulocyte concentration (r = 0.54, p < 0.0001). As
      expected, complement activation was not affected by cell depletion and did not
      correlate with the concentration of any of the cell types. Thus, artificial
      surface-induced IL-8 and LTB4 synthesis was almost exclusively granulocyte
      dependent. However, MCP-1 synthesis was mainly a product of monocytes, although
      granulocytes and other subpopulations may partly contribute. (c) 2005 Wiley
      Periodicals, Inc. J Biomed Mater Res, 2005.

PMID- 15962267
TI  - Microtensile testing of collagen fibril for cardiovascular tissue engineering.
AB  - As a candidate scaffold material for cardiac tissue engineering, Type I collagen
      material shows different mechanical properties due to the differences in the
      structural features such as orientation of fibril alignment and the environmental
      factors such as ultraviolet (UV) irradiation. In this article one-dimensional
      tensile stress tests were performed with the use of a nanoscale tensile tester on
      four groups of Type I collagen samples that were differentiated in terms of
      fibril orientation and/or UV irradiation. The collagen surface structure was
      studied with the use of an atomic force microscope (AFM). Effects of fibril
      orientation and UV irradiation on their mechanical properties were investigated.
      The mechanical properties and deformation mechanisms are discussed in conjunction
      with collagen structure, fibril orientation, and dispersion of the generated
      crosslinking by UV irradiation.

PMID- 15962268
TI  - Influence of deposition parameters on chemical properties of calcium phosphate
      coatings prepared by using electrostatic spray deposition.
AB  - The electrostatic spray deposition (ESD) technique offers the possibility of
      depositing calcium phosphate (CaP) coatings onto various substrate materials with
      defined chemical and morphological properties. The relationship between physical,
      apparatus-related deposition parameters, and the chemical characteristics of ESD
      coatings was investigated by means of X-ray diffraction, Fourier transform
      infrared spectroscopy, and energy dispersive spectroscopy to be able to deposit
      CaP coatings with tailored chemical properties. The results showed that the
      chemical characteristics of CaP coatings, deposited with use of the ESD
      technique, were strongly dependent on the deposition temperature, the nozzle-to
      substrate distance, the liquid flow rate, and the geometry of the spraying
      nozzle. By investigating the influence of the deposition temperature, information
      could be obtained on the formation mechanism of CaP coatings-and specifically the
      biologically interesting carbonate apatite phase-using the ESD technique. CaP
      coatings were not formed merely because of solvent evaporation; a chemical
      reaction was needed to synthesize the coatings. This reaction involved thermal
      decomposition of the organic solvent butyl carbitol into carbonate ions via
      formation of intermediate oxalate ions. The amount of carbonate incorporation,
      and consequently, the Ca/P ratios of the deposited coatings, was shown 1) to
      decrease with increasing nozzle-to-substrate distance, 2) to decrease with
      increasing liquid flow rate, and 3) to decrease by making use of a novel two
      component nozzle geometry.

PMID- 15962269
TI  - Enhanced mineralized tissue adhesion to titanium over polystyrene assessed by the
      nano-scratch test.
AB  - The critical load determined by the scratch test is regarded to be a
      representative measure of coating adhesion in the field of engineering. This
      study aimed to evaluate the method for its usefulness for assessing the
      mineralized tissue-titanium interface strength. Osteoblastic cells derived from
      rat bone marrow were cultured on polystyrene, titanium-coated polystyrene, and
      titanium disks with either a machined or dual-acid etched surface. Nano-scratch
      testing was performed on mineralized tissue specimens at culture day 28. The
      scratch path was monitored by light microscopy until complete delamination of
      mineralized tissue from the substrate occurred, and the required force was
      recorded as the critical load. Energy-dispersive spectroscopic analysis was used
      to verify the delamination. The mean critical load values (+/- standard
      deviations) were as follows: polystyrene 31 mN (+/-1), titanium-coated
      polystyrene 67 mN (+/-4), machined titanium 76 mN (+/-4), DAE titanium 107 mN (+/
      3), with statistical differences (P < 0.05; ANOVA). No elemental calcium and
      phosphorous were observed in the delaminated areas. The nano-scratch test applied
      to cultured mineralized tissue differentiated the critical load from various
      culture conditions: polystyrene vs. titanium; titanium with different surface
      topographies. Culturing mineralized tissue on titanium, especially on roughened
      surfaces, increased the tissue critical load. The nano-scratch test may be useful
      to evaluate mineralized tissue adhesion properties in titanium cultures.

PMID- 15962270
TI  - Radiation synthesis of poly(N-vinyl-2-pyrrolidone)-kappa-carrageenan hydrogels
      and their use in wound dressing applications. I. Preliminary laboratory tests.
AB  - Poly(N-vinyl-2-pyrrolidone)-kappa-carrageenan hydrogels (PVP-KC) were prepared by
      irradiating the mixtures of aqueous solutions of PVP, KC, potassium chloride, and
      poly(ethylene glycol) by gamma-rays at different doses. Their preliminary
      laboratory tests were evaluated to identify their usability in wound dressing
      applications. For investigation of the effect of components on the gelation of
      PVP, sol-gel analyses were made and gel fractions of the hydrogels were
      determined. Mechanical experiments were conducted for both unirradiated and
      irradiated samples. For investigation of the fluid uptake capacity of the
      hydrogels, swelling experiments were performed in pseudo-extracellular fluid
      solution at various temperatures. Acidity/alkalinity (pH) and electrical
      conductivity tests were achieved from aqueous extracts of hydrogels, and
      bioadhesion strength of the hydrogels was investigated on human skin.

PMID- 15962271
TI  - Improving the blood compatibility of polyurethane using carbon nanotubes as
      fillers and its implications to cardiovascular surgery.
AB  - Blood compatibility has been an occlusion for biomaterials used in the
      cardiovascular system. In this work, a multiwalled carbon nanotubes-polyurethane
      composite (MWNT-PU) was prepared through a controlled co-precipitation. The
      surface chemical composition of treated carbon nanotubes was analyzed with XPS
      and the thermal behaviors of composite were characterized by DSC. The platelet
      adhesion and activation caused by the composite were evaluated by using SEM and
      flow cytometric analysis, respectively, and the disruption of red blood cells was
      analyzed through measuring the absorbance of free hemoglobin. The experimental
      results demonstrated that: (1) Multiwalled carbon nanotubes (MWNTs) with oxygen
      containing functional groups could be well dispersed in polyurethane matrix
      through a controlled coprecipitation; (2) the composite surface displayed a
      significantly improved anticoagulant function, which can be indicative of the
      promising potentials of carbon nanotube-based materials in the implants and
      medical devices applied in blood-contacting environments.

PMID- 15962272
TI  - Effects of nano HAP on biological and structural properties of glass bone cement.
AB  - A novel type of glass-based nanoscale hydroxyapatite (HAP) bioactive bone cement
      (designed as GBNHAPC) was synthesized by adding nanoscale hydroxyapatite
      crystalline (20-40 nm), into the self-setting glass-based bone cement (GBC). The
      inhibition rate of nanoscale HAP and micron HAP on osteosarcoma U2-OS cells was
      examined. The effects of nanoscale HAP on the crystal phase, microstructure and
      compressive strength of GBNHAPC were studied, respectively. It was concluded that
      nanoscale HAP could inhibit the cell proliferation, whereas micron HAP could not,
      and that nanoscale HAP could be dispersed in the cement evenly and the morphology
      did not change significantly after a longer immersion time. XRD and FTIR results
      show nanoscale HAP did not affect the setting reaction of the cement.
      Furthermore, GBNHAPC had a higher compressive strength (92.6 +/- 3.8 MPa) than
      GBC (80.1 +/- 3.0 MPa). It was believed that GBNHAPC might be a desirable
      biomaterial that could not only fill bone defects but also inhibit cancer cell
      growth.

PMID- 15962273
TI  - Production of monocyte chemoattractant protein-1 in amyotrophic lateral
      sclerosis.
AB  - The presence of activated microglia in the spinal cord of amyotrophic lateral
      sclerosis (ALS) patients is usually accompanied by inflammatory biochemical
      changes, but these are largely unexplored. Monocyte chemoattractant protein-1
      (MCP-1) is critical for recruitment of inflammatory cells of monocytic lineage
      after inflammation or injury to the central nervous system. MCP-1 concentrations
      were measured by an enzyme-linked immunosorbent assay in the cerebrospinal fluid
      (CSF) and the serum of 27 patients with ALS and 30 patients with noninflammatory
      neurological diseases. In ALS, circulating MCP-1 levels were significantly
      increased in the serum and particularly in the CSF. Immunoreactivity for MCP-1 in
      ALS spinal cord was detected mostly in astrocytes but also in microglia, neurons,
      and within the vasculature of the cord. Our findings suggest a role for MCP-1 as
      an important molecular mediator of the injury response in ALS.

PMID- 15962274
TI  - Accuracy of predicting maximal quadriceps force from submaximal effort
      contractions after anterior cruciate ligament injury.
AB  - Weakness and failure of voluntary activation of the quadriceps femoris muscles
      often occur after anterior cruciate ligament (ACL) rupture. Side-to-side strength
      comparisons are used as a measure of progress, and are inaccurate if the
      quadriceps has activation failure. Burst superimposition testing is commonly used
      to assess quadriceps strength and activation during a maximal volitional
      isometric contraction (MVIC), using the central activation ratio (CAR)
      calculation. A recently developed mathematical model predicts the MVIC from
      submaximal efforts. The purpose of this study was to compare the CAR calculation
      to the mathematical model. We hypothesized that the model would be a more
      accurate predictor of strength than the CAR calculation when voluntary activation
      failure is present. Data from the involved and uninvolved quadriceps muscles of
      100 consecutive subjects with complete, isolated ACL rupture were retrospectively
      evaluated. Subjects who required multiple trials to produce an MVIC with full
      activation (true MVIC) were used to compare the CAR calculation, the mathematical
      model, and this true MVIC. Subjects unable to produce a true MVIC with multiple
      trials were used to compare the mathematical model to the CAR calculation.
      Results demonstrate that both methods reliably and accurately estimate the
      quadriceps weakness associated with ACL rupture. We recommend use of the CAR
      calculation to provide estimations of true quadriceps strength to facilitate
      clinical decisions about progress in rehabilitation after ACL rupture.

PMID- 15962275
TI  - Conformations, energies, and intramolecular hydrogen bonds in dicarboxylic acids:
      implications for the design of synthetic dicarboxylic acid receptors.
AB  - The various conformers of the dicarboxylic acids HO2C--(CH2)n--CO2H, n = 1-4,
      were obtained using density functional methods (DFT), both in the gas phase and
      in the aqueous phase using a polarized continuum model (PCM). Several new
      conformers were identified, particularly for the two larger molecules glutaric (n
      = 3) and adipic acid (n =4). The PCM results show that the stability of most
      conformers were affected, many becoming unstable in the aqueous phase; and the
      energy ordering of conformers is also different. The results suggest that
      conformational preferences could be important in determining the design and
      stability of appropriate synthetic receptors for glutaric and adipic acid.
      Geometry changes between gas and aqueous phases were most marked in those
      conformers containing an intramolecular hydrogen bond. Additional calculations
      have probed the strength of intramolecular hydrogen bonds in these dicarboxylic
      acids. In the cases of glutaric and adipic acid, the strength of the
      intramolecular hydrogen bond were estimated to be around 28-29 kJ/mol, without
      any vibrational energy correction. The intramolecular hydrogen bond energies in
      malonic and succinic acid were also estimated from the calculated H-bond
      distances using an empirical relationship. Intramolecular H-bond redshifts of 170
      250 cm(-1) have been estimated from the results of the harmonic frequency
      analyses.

PMID- 15962276
TI  - Optimization of auxiliary basis sets for the LEDO expansion and a projection
      technique for LEDO-DFT.
AB  - We present a systematic procedure for the optimization of the expansion basis for
      the limited expansion of diatomic overlap density functional theory (LEDO-DFT)
      and report on optimized auxiliary orbitals for the Ahlrichs split valence plus
      polarization basis set (SVP) for the elements H, Li--F, and Na--Cl. A new method
      to deal with near-linear dependences in the LEDO expansion basis is introduced,
      which greatly reduces the computational effort of LEDO-DFT calculations.
      Numerical results for a test set of small molecules demonstrate the accuracy of
      electronic energies, structural parameters, dipole moments, and harmonic
      frequencies. For larger molecular systems the numerical errors introduced by the
      LEDO approximation can lead to an uncontrollable behavior of the self-consistent
      field (SCF) process. A projection technique suggested by Lowdin is presented in
      the framework of LEDO-DFT, which guarantees for SCF convergence. Numerical
      results on some critical test molecules suggest the general applicability of the
      auxiliary orbitals presented in combination with this projection technique.
      Timing results indicate that LEDO-DFT is competitive with conventional density
      fitting methods.

PMID- 15962277
TI  - Adaptation of a fast Fourier transform-based docking algorithm for protein
      design.
AB  - Designing proteins with novel protein/protein binding properties can be achieved
      by combining the tools that have been developed independently for protein docking
      and protein design. We describe here the sequence-independent generation of
      protein dimer orientations by protein docking for use as scaffolds in protein
      sequence design algorithms. To dock monomers into sequence-independent dimer
      conformations, we use a reduced representation in which the side chains are
      approximated by spheres with atomic radii derived from known C2 symmetry-related
      homodimers. The interfaces of C2-related homodimers are usually more hydrophobic
      and protein core-like than the interfaces of heterodimers; we parameterize the
      radii for docking against this feature to capture and recreate the spatial
      characteristics of a hydrophobic interface. A fast Fourier transform-based
      geometric recognition algorithm is used for docking the reduced representation
      protein models. The resulting docking algorithm successfully predicted the wild
      type homodimer orientations in 65 out of 121 dimer test cases. The success rate
      increases to approximately 70% for the subset of molecules with large surface
      area burial in the interface relative to their chain length. Forty-five of the
      predictions exhibited less than 1 A C(alpha) RMSD compared to the native X-ray
      structures. The reduced protein representation therefore appears to be a
      reasonable approximation and can be used to position protein backbones in
      plausible orientations for homodimer design.

PMID- 15962279
TI  - Characterization of the nonregular regions of proteins by a contortion index.
AB  - Nonstructured regions in proteins that provide the link between two regular
      structured regions play a significant role in maintaining the scaffold of the
      protein. Not only do they act as connectors between two regular secondary
      structural elements of proteins but they also provide the necessary turn or
      reversal in the polypeptide chain. This incorporates flexibility in the
      structure. Thus an understanding of the structural aspects of the nonregular
      regions is necessary to have a better insight into these features. We can assume
      the nonregular region to be a contorted polypeptide segment tethered by regular
      secondary structured regions at both ends. To describe the undulating nature of
      the nonregular regions, we introduce a parameter called the "contortion index."
      This index describes how tortuously the region is organized. Our analysis shows
      that the contortion index is related to other physicochemical parameters and can
      be used to characterize the nonregular regions of proteins.

PMID- 15962278
TI  - Lysozyme fibrillation: deep UV Raman spectroscopic characterization of protein
      structural transformation.
AB  - Deep ultraviolet resonance Raman spectroscopy was demonstrated to be a powerful
      tool for structural characterization of protein at all stages of fibril
      formation. The evolution of the protein secondary structure as well as the local
      environment of phenylalanine, a natural deep ultraviolet Raman marker, was
      documented for the fibrillation of lysozyme. Concentration-independent
      irreversible helix melting was quantitatively characterized as the first step of
      the fibrillation. The native lysozyme composed initially of 32% helix transforms
      monoexponentially to an unfolded intermediate with 6% helix with a characteristic
      time of 29 h. The local environment of phenylalanine residues changes
      concomitantly with the secondary structure transformation. The phenylalanine
      residues in lysozyme fibrils are accessible to solvent in contrast to those in
      the native protein.

PMID- 15962280
TI  - Rationalization of the multireceptorial character of chiral solvating agents
      based on quinine and its derivatives: overview of selected NMR investigations.
AB  - A summary of selected NMR studies of enantiodiscrimination phenomena regarding
      the use of quinine-based chiral solvating agents (CSAs) for the determination of
      the enantiomeric compositions in solution is reported, with explanations of their
      multireceptorial character offered.

PMID- 15962281
TI  - Enantioseparation of the esters of alpha-N-acetyl amino acids by lipase in ionic
      liquid.
AB  - Chiral alpha-amino acids have been obtained via enzymatic resolution in ionic
      liquid medium. The acetyl esters of a series of amino acids were separated by
      enzyme porcine pancreas lipase (PPL) in an aqueous solution of N-ethyl pyridinium
      trifluoroacetate, [EtPy]+ [CF3OO]-. A comparative study with organic solvent
      acetonitrile shows that the ionic liquids provide a better medium for enzymatic
      resolution.

PMID- 15962282
TI  - Enantiopure drug synthesis: from methyldopa to imipenem to efavirenz.
AB  - An historical retrospective is presented relative to the development of practical
      processes for the syntheses of three major drugs: methyldopa, imipenem, and
      efavirenz. Each highlights a major method for asymmetric synthesis. This work was
      initially presented as a lecture at the BLOCKBUSTER CHIRALITY section of the
      CHIRALITY 2004 meeting in New York City, and this paper is simply a written
      account of that presentation. The original literature that details the chemistry
      discussed herein is noted in the reference section.

PMID- 15962283
TI  - Supernova antineutrino interactions cause chiral symmetry breaking and possibly
      homochiral biomaterials for life.
AB  - There is some evidence that nonracemic hydrocarbons occur in meteorites. This
      would indicate an extraterrestrial origin of the homochirality in living systems
      (proteins, DNA, RNA). The weak interaction breaks chiral symmetry, but a robust
      process is needed. We propose that, in an SNII explosion, antineutrinos could
      provide this mechanism in the solar cloud. Pre-simple estimates of this
      possibility are given here.

PMID- 15962284
TI  - A viral kinetic study using pegylated interferon alfa-2b and/or lamivudine in
      patients with chronic hepatitis B/HBeAg negative.
AB  - We studied viral dynamic parameters in 44 chronic hepatitis B/hepatitis B e
      antigen (HBeAg)(-) patients treated with pegylated interferon alfa-2b (PEG-IFN)
      100 or 200 microg weekly or lamivudine 100 mg daily or the combination of PEG-IFN
      100 or 200 microg with lamivudine. Patients receiving PEG-IFN monotherapy
      exhibited viral load oscillations between weekly injections, which were resolved
      by the addition of lamivudine. The median pharmacological delay was estimated at
      4.1, 5.8, and 1.8 hours in PEG-IFN monotherapy, PEG-IFN 100/200 microg +
      lamivudine, and lamivudine monotherapy, respectively (P = .44). The median half
      life of free virus was 12.7 hours (range, 2.4-69.2 hours). The mean antiviral
      effectiveness of PEG-IFN 100/200 microg monotherapy was lower than that of
      lamivudine (82.6% vs. 96.4%; P = .005). The mean effectiveness of PEG-IFN 100
      microg + lamivudine and PEG-IFN 200 microg + lamivudine was 92.8% and 94.4%,
      respectively. The half-life of infected cells ranged from 2.7 to 75 days. The
      median half-life of infected cells in patients receiving the combination regimens
      of PEG-IFN and lamivudine was similar to that of lamivudine patients (5.0 days
      vs. 6.0 days, P = .77). In conclusion, the addition of pegylated interferon alfa
      2b in lamivudine treatment was found to neither enhance the potency of blocking
      HBV production nor the decay rates of infected cells. Supplementary material for
      this article can be found on the HEPATOLOGY website
      (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

PMID- 15962285
TI  - Functional analysis of hepatitis B virus reactivating in hepatitis B surface
      antigen-negative individuals.
AB  - The biological properties of latent or occult hepatitis B virus (HBV) have been
      poorly characterized as a result of the extremely low virus concentration. This
      report describes the phenotype of HBV reactivating in two patients after an HBsAg
      negative latency period. One patient had latent HBV infection for at least 12
      years without detectable viremia and symptoms of liver disease. Several full
      length HBV genomes were cloned at reactivation, sequenced, and functionally
      tested by transfection into HuH7 cells. Genomes from both patients showed a low
      replication phenotype. It was caused at the level of RNA encapsidation or HBV DNA
      synthesis, but was not attributable to uncommon mutations in the terminal protein
      domain of P protein. A substantial subpopulation ( approximately 50%) of genomes
      from one patient did not express pre-S2/S mRNA and HBsAg. Site-directed
      mutagenesis identified a single G-A mutation within the S gene (position 458) to
      be responsible for this effect. The G458A mutation was also effective if the S
      gene was placed under control of a heterologous promoter. Furthermore, nuclear
      run-on transcription showed that the G458A mutation acts at the
      posttranscriptional level. The mutation affected a 5' splice site and prevented
      splicing of the pre-S2/S mRNA from position 458 to 1305. In conclusion, HBV
      latency may be characterized by viruses with reduced replication competence and
      antigen expression. In one patient, HBsAg expression was terminated by an as yet
      undescribed posttranscriptional mechanism. A single mutation inactivated a 5'
      splice site that is obviously essential for pre-S2/S mRNA accumulation.
      Supplementary material for this article can be found on the HEPATOLOGY website
      (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

PMID- 15962286
TI  - Induction of the von Hippel-Lindau tumor suppressor gene by late hypoxia limits
      HIF-1 expression.
AB  - Hypoxia-inducible factor (HIF) remains the central focus of oxygen sensing during
      hypoxia. HIF is a heterodimeric transcription factor consisting of an oxygen
      regulated alpha- and a constitutively expressed beta subunit. The von Hippel
      Lindau tumor suppressor (pVHL) is a component of the E3 ubiquitin ligase complex
      and targets HIF-alpha to proteasomal degradation, but also is known to exert a
      significant control on HIF transactivation activity. However, the understanding
      of the full interaction between HIF and pVHL has been hindered by a lack in the
      understanding of pVHL regulation. Here, we report that pVHL itself is induced in
      prolonged hypoxia in a kinetic that parallels the observed downregulation of HIF
      1alpha protein under such conditions. In addition, we document direct HIF-1alpha
      binding to the VHL promoter and identify a functional hypoxia response element
      (HRE) within the VHL promoter. Such induction of pVHL in hypoxia furthermore has
      functional implications for the HIF dependent hypoxic response, implicating a
      physiologically relevant feedback mechanism. These results provide an intriguing
      model, whereby HIF self-regulates expression through VHL and highlight the role
      of pVHL as a unifying mechanism of HIF regulation.

PMID- 15962287
TI  - Role of c-Jun N-terminal kinase in the PDGF-induced proliferation and migration
      of human adipose tissue-derived mesenchymal stem cells.
AB  - Platelet-derived growth factor (PDGF) is a critical regulator of proliferation
      and migration for mesenchymal type cells. In this study, we examined the role of
      mitogen-activated protein (MAP) kinases in the PDGF-BB-induced proliferation and
      migration of human adipose tissue-derived mesenchymal stem cells (hATSCs). The
      PDGF-induced proliferation was prevented by a pretreatment with the c-Jun N
      terminal kinase (JNK) inhibitor, SP600125. However, it was not prevented by a
      pretreatment with a p38 MAP kinase inhibitor, SB202190, and a specific inhibitor
      of the upstream kinase of extracellular signal-regulated kinase (ERK1/2), U0126.
      Treatment with PDGF induced the activation of JNK and ERK in hATSCs, and
      pretreatment with SP600125 specifically inhibited the PDGF-induced activation of
      JNK. Treatment with PDGF induced the cell cycle transition from the G0/G1 phase
      to the S phase, the elevated expression of cyclin D1, and the phosphorylation of
      Rb, which were prevented by a pretreatment with SP600125. In addition, the PDGF
      induced migration of hATSCs was completely blocked by a pretreatment with
      SP600125, but not with U0126 and SB202190. These results suggest that JNK protein
      kinase plays a key role in the PDGF-induced proliferation and migration of
      mesenchymal stem cells.

PMID- 15962288
TI  - Myosin light chain kinase and acto-myosin contractility modulate activation of
      the ERK cascade downstream of oncogenic Ras.
AB  - The actin cytoskeleton is recognized as an important component of both adhesion-
      and growth factor-dependent signaling, but its role in oncogene-dependent
      signaling has received much less attention. In this study, we investigated the
      role played by the acto-myosin cytoskeleton and its main regulators, i.e., myosin
      light chain kinase and Rho kinase, in oncogenic Ki-Ras-induced signaling. We
      found that activation of the ERK cascade by Ras is dependent on acto-myosin
      contractility, under the regulation of myosin light chain kinase but not Rho
      kinase. Inhibition of myosin II or myosin light chain kinase caused a complete
      loss of ERK phosphorylation in a time- and dose-dependent manner, but proved
      dispensable for activation of the PI3K pathway. We also provide evidence that the
      target of myosin light chain kinase lays at the level of Raf activation. Since
      myosin light chain kinase is a target of ERK, these results suggest a previously
      uncharacterized signaling pathway involving Ras-mediated alterations of the actin
      cytoskeleton, which might play a critical role in ERK activation by the Ras
      oncogene and contribute to aberrant signaling and enhanced cell motility. In
      addition, restoration of stress fibers following ectopic expression of
      tropomyosin 2 resulted in reduced levels of ERK phosphorylation. Finally, these
      studies suggest that myosin light chain kinase but not Rho kinase plays an
      essential role in the generation of ERK signaling in transformed cells and
      indicate distinct cellular roles for Rho-kinase and myosin light chain kinase
      dependent functions involving the regulation of acto-myosin contractility.

PMID- 15962289
TI  - Comprehensive analyses of CD8+ T cell responses during longitudinal study of
      acute human hepatitis C.
AB  - We comprehensively studied the cellular immune response during acute human
      hepatitis C virus (HCV) infection by monthly prospective sampling of persons at
      high risk of infection. In 19 of 23 subjects, interferon-gamma-secreting T cells
      specific for 1 or more peptides spanning the entire HCV polyprotein were detected
      1 to 3 months after infection. The median time to development of interferon gamma
      responses to HCV peptides was 33 days (range, 29-50 days), and these responses
      peaked between 180 and 360 days. Nineteen subjects had sufficient follow-up to
      determine outcome, with 15 (79%) developing persistent viremia and 4 (21%)
      clearing viremia spontaneously. Of those with progression to chronic infection
      and detectable T cell responses, all lost recognition of one or more antigens
      recognized during acute infection, and the median reduction in the magnitude of
      responses was 85%. Most significantly, despite ongoing viremia, those who had
      persistent infection did not develop new epitope specificities after the first 6
      months of infection. In conclusion, in most individuals, the CD8+ T cell
      responses generated early in HCV infection decline in peripheral blood and are
      not replaced with new responses. Supplementary material for this article can be
      found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 15962290
TI  - Effects of parathyroid hormone on Wnt signaling pathway in bone.
AB  - The Wnt signaling pathway has recently been demonstrated to play an important
      role in bone cell function. In previous studies using DNA microarray analyses, we
      observed a change in some of the molecular components of the canonical Wnt
      pathway namely, frizzled-1 (FZD-1) and axil, in response to continuous
      parathyroid hormone (PTH) treatment in rats. In the present study, we further
      explored other components of the Wnt signaling pathway in rat distal metaphyseal
      bone in vivo, and rat osteoblastic osteosarcoma cells (UMR 106) in culture.
      Several Wnt pathway components, including low-density lipoprotein-receptor
      related protein 5 (LRP5), LRP6, FZD-1, Dickkopf-1 (Dkk-1), and Kremen-1 (KRM-1),
      were expressed in bone in vivo and in osteoblasts in vitro. Continuous exposure
      to PTH (1-38) both in vivo and in vitro upregulated the mRNA expression of LRP6
      and FZD-1 and decreased LRP5 and Dkk-1. These effects in UMR 106 cells were
      associated with an increase in beta-catenin as measured by Western blots and
      resulted in functional activation (three to six-fold) of a downstream Wnt
      responsive TBE6-luciferase (TCF/LEF-binding element) reporter gene. Activation of
      the TBE6-luciferase reporter gene by PTH (1-38) in UMR 106 cells was inhibited by
      the protein kinase A (PKA) inhibitor, H89. Activation was mimicked by PTH (1-31),
      PTH-related protein (1-34), and forskolin, but both PTH (3-34) and (7-34) had no
      effect. These findings suggest that the effect of PTH on the canonical Wnt
      signaling pathway occurs at least in part via the cAMP-PKA pathway through the
      differential regulation of the receptor complex proteins (FZD-1/LRP5 or LRP6) and
      the antagonist (Dkk-1). Taken together, these results reveal a possible role for
      the Wnt signaling pathway in PTH actions in bone.

PMID- 15962291
TI  - Outcome of hepatitis B e antigen-negative chronic hepatitis B on long-term
      nucleos(t)ide analog therapy starting with lamivudine.
AB  - We determined the clinical outcome of hepatitis e antigen (HBeAg)-negative
      chronic hepatitis B patients treated with long-term nucleos(t)ide analog therapy
      starting with lamivudine. We evaluated 201 such patients treated for 3.8 +/- 1.4
      years and 2 historical similar cohorts: 1 treated with interferon-alfa (n = 209)
      and 1 untreated (n = 195). Virological or biochemical remission rate at 48 months
      under lamivudine was 34% or 36%, respectively, whereas adefovir was administered
      in 79 patients with virological-biochemical breakthroughs or no response. Of the
      lamivudine-treated patients, 4 died, 1 underwent a transplantation, and another 8
      developed major events, all having advanced fibrosis at baseline and all but 1
      having experienced breakthroughs or no response. At 5 years, survival was 96%,
      and major event-free survival was 93%. The major event-free survival was
      significantly better in patients with than in those without virological remission
      under lamivudine. At the end of follow-up, both survival and major event-free
      survival were independently associated with type of and response to treatment,
      being significantly better in patients under long-term antiviral therapy or
      interferon sustained responders than in interferon non-sustained responders or
      untreated cases (5-year survival: 96% or 98% vs. 88% or 90%, respectively). In
      conclusion, in HBeAg-negative chronic hepatitis B, long-term nucleos(t)ide analog
      therapy starting with lamivudine significantly improves survival and reduces the
      risk of major complications, compared with interferon non-sustained responders or
      untreated patients. In such patients with advanced fibrosis, close follow-up for
      lamivudine resistance and prompt onset of additional antiviral therapy is
      required or the ab initio use of agent(s) with low resistance rates should be
      considered.

PMID- 15962292
TI  - Oxidative mitochondrial DNA damage and deletion in hepatocytes of rejecting liver
      allografts in rats: role of TNF-alpha.
AB  - An orthotopic liver transplant model in the rat was used to evaluate the role of
      tumor necrosis factor alpha (TNF-alpha) in liver transplant rejection. There were
      significantly increased levels of TNF-alpha mRNA and parallel increases in 8
      hydroxy-2' deoxyguanosine (8-OHdG) indicative of oxidative DNA damage present 7
      to 12 days after transplantation. Cells staining positively for 8-OHdG were
      localized to the cytoplasm of hepatocytes adjacent to the TNF-alpha expressing
      inflammatory cells in the portal areas or in patches surrounded by inflammatory
      cells in the hepatic sinusoids. Significantly more cells staining for 8-OHdG were
      found in the allogeneic grafts that were strongly rejected than in the syngeneic
      controls or in the grafts placed in species that accepted the allograft
      permanently after a rejection episode. TUNEL reactivity lagged 2 days behind peak
      reactivity for 8-OHdG. On day 12 after transplantation, many cells stained for
      both 8-OHdG and TUNEL, indicating that the cells suffering oxidative DNA injury
      were undergoing apoptosis or death. Oxidative injury resulted in mtDNA deletion
      consisting of 4,834 base-pairs. Studies of hepatocytes cultured from normal rats
      displayed dose-dependent relationships between TNF-alpha concentration and 8-OHdG
      and mtDNA mutation. Repetitive intraperitoneal injection of Enbrel, a TNF
      receptor blocker, significantly decreased hepatocyte 8-OHdG levels and the
      frequency of deleted mtDNA while greatly extending graft survival time. In
      conclusion, the data presented implicate TNF-alpha as being capable of causing
      oxidative DNA damage and mtDNA mutation in hepatocytes.

PMID- 15962293
TI  - Activation and function of hepatocyte NF-kappaB in postischemic liver injury.
AB  - The inhibitor of NF-kappaB (I-kappaB) kinase (IKK) complex consists of 3
      subunits, IKK1, IKK2, and NF-kappaB essential modulator (NEMO), and is involved
      in the activation of NF-kappaB by various stimuli. IKK2 or NEMO constitutive
      knockout mice die during embryogenesis as a result of massive hepatic apoptosis.
      Therefore, we examined the role of IKK2 in TNF-induced apoptosis and
      ischemia/reperfusion (I/R) injury in the liver by using conditional knockout
      mice. Hepatocyte-specific ablation of IKK2 did not lead to impaired activation of
      NF-kappaB or increased apoptosis after TNF-alpha stimulation whereas conditional
      NEMO knockout resulted in complete block of NF-kappaB activation and massive
      hepatocyte apoptosis. In a model of partial hepatic I/R injury, mice lacking IKK2
      in hepatocytes displayed significantly reduced liver necrosis and inflammation
      than wild-type mice. AS602868, a novel chemical inhibitor of IKK2, protected mice
      from liver injury due to I/R without sensitizing them toward TNF-induced
      apoptosis and could therefore emerge as a new pharmacological therapy for liver
      resection, hemorrhagic shock, or transplantation surgery.

PMID- 15962294
TI  - Is the FXR the fix for cholesterol gallstone disease?
AB  - Cholesterol gallstone disease is characterized by several events, including
      cholesterol precipitation in bile, increased bile salt hydrophobicity and
      gallbladder inflammation. Here, we describe the same phenotype in mice lacking
      the bile acid receptor, FXR. Furthermore, in susceptible wild-type mice that
      recapitulate human cholesterol gallstone disease, treatment with a synthetic FXR
      agonist prevented sequelae of the disease. These effects were mediated by FXR
      dependent increases in biliary bile salt and phospholipid concentrations, which
      restored cholesterol solubility and thereby prevented gallstone formation. Taken
      together, these results indicate that FXR is a promising therapeutic target for
      treating or preventing cholesterol gallstone disease.

PMID- 15962296
TI  - TIPS for veno-occlusive disease: is the contraindication real?

PMID- 15962299
TI  - PDGF-BB induces vascular smooth muscle cell expression of high molecular weight
      FGF-2, which accumulates in the nucleus.
AB  - Basic fibroblast growth factor (FGF-2) and platelet-derived growth factor (PDGF)
      are implicated in vascular remodeling secondary to injury. Both growth factors
      control vascular endothelial and smooth muscle cell proliferation, migration, and
      survival through overlapping intracellular signaling pathways. In vascular smooth
      muscle cells PDGF-BB induces FGF-2 expression. However, the effect of PDGF on the
      different forms of FGF-2 has not been elucidated. Here, we report that treatment
      of vascular aortic smooth muscle cells with PDGF-BB rapidly induces expression of
      20.5 and 21 kDa, high molecular weight (HMW) FGF-2 that accumulates in the
      nucleus and nucleolus. Conversely, PDGF treatment has little or no effect on 18
      kDa, low-molecular weight FGF-2 expression. PDGF-BB-induced upregulation of HMW
      FGF-2 expression is controlled by sustained activation of extracellular signal
      regulated kinase (ERK)-1/2 and is abolished by actinomycin D. These data describe
      a novel interaction between PDGF-BB and FGF-2, and indicate that the nuclear
      forms of FGF-2 may mediate the effect of PDGF activity on vascular smooth muscle
      cells.

PMID- 15962300
TI  - Characterisation of the transcription factor, SIX5, using a new panel of
      monoclonal antibodies.
AB  - SIX5 is a member of the human SIX family of transcription factors, many of which
      are involved in eye development. However, SIX5 transcripts are known to be
      present at very low levels in cells and no study has yet convincingly
      demonstrated detection of endogenous SIX5 protein by Western blotting or
      immunolocalisation. We have produced a new panel of 18 monoclonal antibodies
      (mAbs) that recognise at least four different epitopes in order to identify
      authentic human SIX5 protein in cells and tissues. Phage-displayed peptide
      libraries were used to identify individual amino-acids important for antibody
      binding within each epitope. Endogenous SIX5 migrated in SDS-PAGE with an
      apparent M(r) of 100 kDa and was present at similar levels in all foetal tissues
      and cell lines tested. In HeLa cells, it was located in the nucleoplasm with a
      granular distribution. An mRNA for a shorter splicing isoform of SIX5, with an
      altered carboxy-terminus, has been described, but further mAbs specific for this
      isoform did not detect any endogenous protein. We conclude that the full-length
      isoform is the major functional protein in vivo while the putative shorter
      protein is undetectable and may not be expressed at all.

PMID- 15962301
TI  - EAST interacts with Megator and localizes to the putative spindle matrix during
      mitosis in Drosophila.
AB  - We have used immunocytochemistry to demonstrate that the EAST protein in
      Drosophila, which forms an expandable nuclear endoskeleton at interphase,
      redistributes during mitosis to colocalize with the spindle matrix proteins,
      Megator and Skeletor. EAST and Megator also colocalize to the intranuclear space
      surrounding the chromosomes at interphase. EAST is a novel protein that does not
      have any previously characterized motifs or functional domains. However, we show
      by immunoprecipitation experiments that EAST is likely to molecularly interact
      with Megator which has a large NH2-terminal coiled-coil domain with the capacity
      for self assembly. On the basis of these findings, we propose that Megator and
      EAST interact to form a nuclear endoskeleton and as well are important components
      of the putative spindle matrix complex during mitosis.

PMID- 15962303
TI  - beta-cryptoxanthin stimulates cell differentiation and mineralization in
      osteoblastic MC3T3-E1 cells.
AB  - The effect of beta-cryptoxanthin, a kind of carotenoid, on cell differentiation
      and mineralization in osteoblastic MC3T3-E1 cells was investigated. Cells were
      cultured for 72 h in a minimum essential medium containing 10% fetal bovine serum
      (FBS), and the cells with subconfluency were changed to a medium containing
      either vehicle or beta-cryptoxanthin (10(-8) to 10(-6) M) without FBS. Cells were
      cultured for 3 to 21 days. Gene expression in osteoblastic cells was determined
      using reverse transcription-polymerase chain reaction (RT-PCR). Culture with beta
      cryptoxanthin (10(-7) or 10(-6) M) for 3 days caused a significant increase in
      Runx2 type 1, Runx2 type 2, alpha1 (I) collagen, and alkaline phosphatase mRNA
      levels in osteoblastic cells. These increases were completely blocked in the
      presence of cycloheximide, an inhibitor of protein synthesis, or 5,6-dichloro-1
      beta-D-ribofuranosylbenzimidazole (DRB), an inhibitor of transcriptional
      activity. Meanwhile, vitamin A (10(-6) M) did not have a significant effect on
      Runx2 type 1 mRNA expression in the cells. The effect of beta-cryptoxanthin (10(
      6) M) in stimulating Runx2 type 1 and alpha1 (I) collagen mRNA levels, protein
      content, and alkaline phosphatase activity in the cells was also seen in the
      presence of vitamin A (10(-6) M), suggesting that the mode of beta-cryptoxanthin
      action differs from that of vitamin A. Prolonged culture with beta-cryptoxanthin
      (10(-6) M) for 3 to 21 days caused a significant increase in cell number,
      deoxyribonucleic acid (DNA) content, protein content, and alkaline phosphatase
      activity in osteoblastic cells, suggesting that beta-cryptoxanthin stimulates
      cell proliferation and differentiation. Moreover, culture with beta-cryptoxanthin
      (10(-7) or 10(-6) M) for 5 to 21 days caused a remarkable increase in
      mineralization. This study demonstrates that beta-cryptoxanthin has a stimulatory
      effect on cell differentiation and mineralization due to enhancing gene
      expression of proteins, which involve in bone formation in osteoblastic MC3T3-E1
      cells.

PMID- 15962302
TI  - Arsenic trioxide (As2O3) inhibits invasion of HT1080 human fibrosarcoma cells:
      role of nuclear factor-kappaB and reactive oxygen species.
AB  - In order to define the role of As2O3 in regulating the tumor cell invasiveness,
      the effects of As2O3 on secretion of matrix metalloproteinases (MMPs) and
      urokinase plasminogen activator (uPA), and in vitro invasion of HT1080 human
      fibrosarcoma cells were examined. As2O3 inhibited cell adhesion to the collagen
      matrix in a concentration dependent manner, whereas the same treatment enhanced
      cell to cell interaction. In addition, As2O3 inhibited migration and invasion of
      HT1080 cells stimulated with phorbol 12-myristate 13-aceate (PMA), and suppressed
      the expression of MMP-2, -9, membrane type-1 MMP, uPA, and uPA receptor (uPAR).
      In contrast, As2O3 increased the expression of tissue inhibitor of
      metalloproteinase (TIMP)-1 and PA inhibitor (PAI)-1, and reduced the MMP-2, -9,
      and uPA promoter activity in the presence and absence of PMA. Furthermore, the
      promoter stimulating and DNA binding activity of nuclear factor-kappaB (NF
      kappaB) was blocked by As2O3, whereas the activator protein-1 activity was
      unchanged. Pretreatment of the cells with N-acetyl-L-cysteine (NAC) significantly
      prevented suppression of MMPs and uPA secretion, DNA binding activity of NF
      kappaB, and in vitro invasion of HT1080 cells by As2O3, suggesting a role of
      reactive oxygen species (ROS) in this process. These results suggest that As2O3
      inhibits tumor cell invasion by modulating the MMPs/TIMPs and uPA/uPAR/PAI
      systems of extracellular matrix (ECM) degradation. In addition, the generation of
      ROS and subsequent suppression of NF-kappaB activity by As2O3 might partly be
      responsible for the phenomena. Overall, As2O3 shows potent activity controlling
      tumor cell invasiveness in vitro.

PMID- 15962304
TI  - Topoisomerase inhibitor induced dephosphorylation of H1 and H3 histones as a
      consequence of cell cycle arrest.
AB  - Posttranslational modifications of histones have an integral function in the
      structural and functional organization of chromatin. Several changes in the
      modification state of histones could be observed after induction of apoptosis
      with topoisomerase inhibitors and other inducers. Most of these studies include
      the analysis of the state of phosphorylation of histones, and the results are to
      some extent controversial, depending on cell lines and agents used. In the
      present study we compared the kinetics of the dephosphorylation of H1 and H3
      histones with apoptosis markers after treatment of leukemic cell lines with
      topoisomerase inhibitors. In parallel, we determined cell cycle parameters in
      detail. Dephosphorylation of both histone classes started within 1 h of
      induction, and no direct correlation with timing and intensity of the
      investigated apoptotic features could be observed. In contrast, we show that the
      effect of topoisomerase inhibitors on the state of H1 and H3 phosphorylation is
      not directly related to apoptosis, but reflects the changes in the cell cycle
      distribution of cells treated with these inducers.

PMID- 15962305
TI  - Compartmentalization of hnRNP-K during cell cycle progression and its interaction
      with calponin in the cytoplasm.
AB  - Coronary artery blockage, due to cardiovascular disease, is routinely treated by
      either balloon-angioplasty or bypass surgery. The limited success of these
      clinical interventions is due at least in part to smooth muscle cell (SMC)
      proliferation. Here we show that heterogeneous nuclear ribonucleoprotein complex
      K (hnRNP-K) protein levels increase in SMC with response to serum stimulation in
      vitro, in the aortas from an animal model of atherosclerosis, and in occluded
      human vein segments. hnRNP-K is a multi-functional protein that has been studied
      primarily in cancer cells and has been suggested to play a role in cell cycle
      progression. We show that in untransformed, cultured SMC, hnRNP-K protein sub
      cellular localization modulates through the cell cycle in both the cytoplasm and
      nucleus. Using cycloheximide, we observed that cytoplasmic accumulation of hnRNP
      K protein at later time points in the cell cycle occurred with a concomitant
      decrease in nuclear hnRNP-K protein, suggesting a translocation of nuclear hnRNP
      K protein to the cytoplasm. Also, because we did not observe an increase in hnRNP
      K protein at early time points in the cell cycle in the presence of
      cycloheximide, we propose that the early increase in cytoplasmic hnRNP-K protein
      following serum stimulation is due to new hnRNP-K protein synthesis. When present
      in the cytoplasm, hnRNP-K is part of a multi-protein complex that consists of at
      least two other proteins, calponin and ERK1/2. Our findings from this study are
      intriguing because they suggest that cytoplasmic hnRNP-K in SMC is part of a
      signaling complex that may be involved in growth-stimulated post-transcriptional
      regulation.

PMID- 15962306
TI  - Virtual reality of stem cell transplantation to repair injured myocardium.
AB  - The search for the fountain of youth continues into the 21st century with hopes
      that embryonic or hematopoietic stem cells (SC) will repair injured tissues in
      the heart, lungs, pancreas, muscles, nerves, liver, or skin. This commentary
      focuses on the potential of SC for inducing cardiac regeneration after myocardial
      injury, the barriers to SC treatment that need to be overcome for ensuring
      successful cardiac repair, and the experimental approaches that can be applied to
      the problem.

PMID- 15962308
TI  - alpha5beta1 integrin stimulates Bcl-2 expression and cell survival through Akt,
      focal adhesion kinase, and Ca2+/calmodulin-dependent protein kinase IV.
AB  - CHO cells expressing alpha5beta1 integrin are more resistant to apoptosis and
      express more Bcl-2 than the same cells engineered to express alphavbeta1 or
      cytoplasmically truncated alpha5Deltacbeta1 integrin as their main fibronectin
      receptor. The Bcl-2 up-regulation by alpha5beta1 is mediated, at least in part,
      by the focal adhesion kinase (FAK) and phosphatidylinositol-3 kinase (PI3K)/Akt
      pathways. Here, we show that integrin-mediated activation of Ca2+/calmodulin
      dependent protein kinase (CaMK) IV, and the NF-kappaB and CREB transcription
      factors also enhance the integrin-dependent regulation of Bcl-2 expression in the
      alpha5beta1cells. A forkhead transcription factor, which is inactivated by Akt,
      blocked Bcl-2 expression. The FAK pathway was found to be defective in both the
      alphavbeta1 and alpha5Deltacbeta1 cells. These cell lines differed from one
      another in two Bcl-2-regulating pathways: adhesion through alphavbeta1 failed to
      activate Akt, allowing forkhead to suppress Bcl-2 transcription, whereas
      alpha5Deltacbeta1 did not activate NF-kappaB and CREB, presumably because CaMK IV
      was not activated. Our results indicate that three pathways, the FAK, PI3K/Akt,
      and CaMK IV mediate the survival-supporting activity of alpha5beta1 integrin.

PMID- 15962307
TI  - Wnt-mediated regulation of chondrocyte maturation: modulation by TGF-beta.
AB  - Wnt proteins are expressed during limb morphogenesis, yet their role and
      mechanism of action remains unclear during long bone growth. Wnt expression,
      effects and modulation of signaling events by BMP and transforming growth factor
      beta (TGF-beta) were evaluated in chick embryonic chondrocytes. Chondrocyte cell
      cultures underwent spontaneous maturation with increased expression of colX and
      this was associated with an increase in the expression of multiple Wnts,
      including Wnt 4, 5a, 8c, and 9a. Both parathyroid hormone related peptide (PTHrP)
      and TGF-beta inhibited colX, but had disparate effects on Wnt expression. While
      TGF-beta strongly inhibited all Wnts, PTHrP did not inhibit either Wnt8c or Wnt9a
      and had lesser effects on the expression of the other Wnts. BMP-2 induced colX
      expression, and also markedly increased Wnt8c expression. Overexpression of beta
      catenin and/or T cell factor (TCF)-4 also induced the type X collagen promoter.
      Overexpression of Wnt8c induced maturation, as did overexpression of beta
      catenin. The Wnt8c/beta-catenin maturational effects were enhanced by BMP-2 and
      inhibited by TGF-beta. TGF-beta also inhibited activation of the Topflash
      reporter by beta-catenin, suggesting a direct inhibitory effect since the
      Topflash reporter contains only beta-catenin binding sequences. In turn beta
      catenin inhibited activation of the p3TP-Luc reporter by TGF-beta, although the
      effect was partial. Thus, Wnt/beta-catenin signaling is a critical regulator of
      the rate of chondrocyte differentiation. Moreover, this pathway is modulated by
      members of the TGF-beta family and demonstrates the highly integrated nature of
      signals controlling endochondral ossification.

PMID- 15962309
TI  - Comparison of staging systems for HCC: one more positive answer or mission
      impossible?

PMID- 15962310
TI  - Reactivation of viral replication after replacement of tenofovir by adefovir.

PMID- 15962311
TI  - Murine liver antigen presenting cells control suppressor activity of CD4+CD25+
      regulatory T cells.
AB  - CD4(+)CD25(+) regulatory T cells (Treg) are important mediators of peripheral
      immune tolerance; however, whether Treg participate also in hepatic immune
      tolerance is not clear. Therefore, we tested the potential of Treg to suppress
      stimulation of CD4(+) T cells by liver sinusoidal endothelial cells (LSEC),
      Kupffer cells (KC), or hepatocytes. In the absence of Treg, all 3 types of liver
      cells could stimulate CD4(+) T cell proliferation; in the presence of Treg,
      however, CD4(+) T cell proliferation was suppressed. Interaction with KC even
      stimulated the expansion of the Treg population; LSEC or hepatocytes, in
      contrast, could not induce proliferation of Treg. Because liver inflammation can
      be induced by infection, we tested the potential of liver cells to modify Treg
      suppressor activity in the presence of microbial signals. In the presence of
      immune-stimulatory CpG-oligonucleotides, LSEC, KC, and hepatocytes could indeed
      overcome Treg-mediated suppression; in the presence of lipopolysaccharide (LPS),
      however, only KC and hepatocytes, but not LSEC, could overcome Treg suppressor
      activity. Hepatocytes from mice with deficient toll-like receptor-4 signaling
      failed to abrogate Treg suppression in response to LPS, indicating that
      overcoming Treg suppressor activity was indeed a response of the liver cell and
      not of the Treg. In conclusion, Treg can suppress CD4(+) T cell stimulation by
      liver cells. However, in response to microbial signals, the liver cells can
      overcome the suppressive activity of Treg. Thus, liver cells may facilitate the
      transition from hepatic immune tolerance to hepatic inflammation by controlling
      Treg suppressor activity.

PMID- 15962312
TI  - Methionine aminopeptidases type I and type II are essential to control cell
      proliferation.
AB  - The dependence of cell growth on methionine aminopeptidase (MetAP) function in
      bacteria and yeast is firmly established. Here we report experimental evidence
      that the control of cell proliferation in mammalian cells is directly linked and
      strictly dependent on the activity of both MetAP-1 and MetAP-2. The targeted
      downregulation of either methionine aminopeptidase MetAP-1 or MetAP-2 protein
      expression by small interfering RNA (siRNA) significantly inhibited the
      proliferation of human umbilical vein endothelial cells (HUVEC) (70%-80%), while
      A549 human lung carcinoma cell proliferation was less inhibited (20%-30%). The
      cellular levels of MetAP-2 enzyme were measured after MetAP-2 siRNA treatment and
      found to decrease over time from 4 to 96 h, while rapid and complete depletion of
      MetAP-2 enzyme activity was observed after 4 h treatment with two pharmacological
      inhibitors of MetAP-2, PPI-2458 and fumagillin. When HUVEC and A549 cells were
      treated simultaneously with MetAP-2 siRNA and PPI-2458, or fumagillin, which
      irreversibly inhibit MetAP-2 enzyme activity, no additive effect on maximum
      growth inhibition was observed. This strongly suggests that MetAP-2 is the single
      critical cellular enzyme affected by either MetAP-2 targeting approach. Most
      strikingly, despite their significantly different sensitivity to growth
      inhibition after targeting of either MetAP-1 or MetAP-2, HUVEC, and A549 cells,
      which were made functionally deficient in both MetAP-1 and MetAP-2 were
      completely or almost completely inhibited in their growth, respectively. This
      closely resembled the observed growth inhibition in genetically double-deficient
      map1map2 yeast strains. These results suggest that MetAP-1 and MetAP-2 have
      essential functions in the control of mammalian cell proliferation and that MetAP
      dependent growth control is evolutionarily highly conserved.

PMID- 15962314
TI  - FRNK, the autonomously expressed C-terminal region of focal adhesion kinase, is
      uniquely regulated in vascular smooth muscle: analysis of expression in
      transgenic mice.
AB  - FRNK, the autonomously expressed carboxyl-terminal region of focal adhesion
      kinase (FAK), is expressed in tissues that are rich in vascular smooth muscle
      cells (VSMCs). Here we report the generation of transgenic mice harboring the
      putative FRNK promoter fused to LacZ and examine the promoter activity in situ
      via expression of beta-galactosidase. The transgenic mice exhibited expression of
      beta-galactosidase predominantly in arterial VSMCs in large and small blood
      vessels of major organs. Upregulation of beta-galactosidase activity was observed
      in tunica media following carotid injury, indicating that the FRNK promoter is
      activated in VSMCs in response to injury. Robust expression of beta-galactosidase
      in blood vessels was also detected in the developing embryo. However, expression
      was also observed in the midline, the nose and skin epidermis, indicating
      distinct transcriptional regulation of the FRNK promoter in embryogenesis. To
      analyze FRNK expression in vitro, we identified a 116 bp sequence in the FRNK
      promoter that was sufficient to function as an enhancer when fused to the minimal
      actin promoter and expressed in cultured smooth muscle cells. Mutation of AP-1
      and NF-E2 binding consensus sequences within this element abrogated enhancer
      activity, supporting the involvement of this promoter element in VSMC expression
      of FRNK.

PMID- 15962315
TI  - Overexpression of regucalcin suppresses cell proliferation in cloned rat hepatoma
      H4-II-E cells: involvement of intracellular signaling factors and cell cycle
      related genes.
AB  - The role of regucalcin, which is a regulatory protein in intracellular signaling
      pathway, in the regulation of cell proliferation was investigated by using the
      cloned rat hepatoma H4-II-E cells overexpressing regucalcin. The hepatoma cells
      (wild type) and stable regucalcin/pCXN2 transfectants were cultured for 72 h in a
      medium containing 10% fetal bovine serum (FBS) to obtain subconfluent
      monolayters. The proliferation of cells was significantly suppressed in
      transfectants cultured for 24-72 h. The proliferation of wild-type cells was
      significantly inhibited when the cells were cultured for 72 h in a medium
      containing an inhibitor of transcriptional activity or protein synthesis. Such an
      effect was not seen in transfectants. The presence of various inhibitors of
      protein kinase including PD 98059 (10(-7) or 10(-6) M), dibucaine (10(-6) M),
      wortmannin (10(-8) or 10(-6) M), or genistein (10(-5) M) caused a significant
      inhibition of the proliferation of wild-type cells. These inhibitory effects were
      not seen in transfectants. Staurosporine (10(-8) - 10(-7) M) significantly
      inhibited the proliferation of wild-type cells and transfectants. Also, the
      effect of vanadate (10(-5) M), an inhibitor of protein tyrosine phosphatase, or
      Bay K 8644 (10(-6) M), an agonist of calcium entry into cells, in inhibiting the
      proliferation of wild-type cells was not observed in transfectants. Moreover, the
      proliferation of wild-type cells was significantly inhibited in the presence of
      roscovitine (10(-7) or 10(-6) M) or sulforaphane (10(-7) M), which induces cell
      cycle arrest. Such effect was not seen in transfectants. The inhibitory effect of
      sodium butyrate (8.3 x 10(-4) M) on proliferation of wild-type cells was also
      induced in transfectants. Gene expression in hepatoma cells cultured for 72 h
      with 10% FBS was determined by using reverse transcription-polymerase chain
      reaction (RT-PCR). The expression of p21 mRNA was significantly enhanced in
      transfectants, while cdc2a and chk2 mRNA expression were not significantly
      changed. Insulin-like growth factor-I (IGF-I) mRNA expression was significantly
      suppressed in transfectants. This study demonstrates that overexpression of
      regucalcin has a suppressive effect on cell proliferation that is partly mediated
      through various intracellular signaling-related factors, and that the effect may
      be partly involved in the change in p21 or IGF-I mRNA expression. The finding
      further supports that regucalcin plays an important role as a suppressor in the
      enhancement of cell proliferation.

PMID- 15962313
TI  - Osteoblast calcium-sensing receptor has characteristics of ANF/7TM receptors.
AB  - There is evidence for a functionally important extracellular calcium-sensing
      receptor in osteoblasts, but there is disagreement regarding its identity.
      Candidates are CASR and a putative novel calcium-sensing receptor, called
      Ob.CASR. To further characterize Ob.CASR and to distinguish it from CASR, we
      examined the extracellular cation-sensing response in MC3T3-E1 osteoblasts and in
      osteoblasts derived from CASR null mice. We found that extracellular cations
      activate ERK and serum response element (SRE)-luciferase reporter activity in
      osteoblasts lacking CASR. Amino acids, but not the calcimimetic NPS-R568, an
      allosteric modulator of CASR, also stimulate Ob.CASR-dependent SRE-luciferase
      activation in MC3T3-E1 osteoblasts. In addition, we found that the dominant
      negative Galphaq(305-359) construct inhibited cation-stimulated ERK activation,
      consistent with Ob.CASR coupling to Galphaq-dependent pathways. Ob.CASR is also a
      target for classical GPCR desensitization mechanisms, since beta-arrestins, which
      bind to and uncouple GRK phosphorylated GPCRs, attenuated cation-stimulated SRE
      luciferase activity in CASR deficient osteoblasts. Finally, we found that Ob.CASR
      and CASR couple to SRE through distinct signaling pathways. Ob.CASR does not
      activate RhoA and C3 toxin fails to block Ob.CASR-induced SRE-luciferase
      activity. Mutational analysis of the serum response factor (SRF) and ternary
      complex factor (TCF) elements in SRE demonstrates that Ob.CASR predominantly
      activates TCF-dependent mechanisms, whereas CASR activates SRE-luciferase mainly
      through a RhoA and SRF-dependent mechanism. The ability of Ob.CASR to sense
      cations and amino acids and function like a G-protein coupled receptor suggests
      that it may belong to the family of receptors characterized by an evolutionarily
      conserved amino acid sensing motif (ANF) linked to an intramembranous 7
      transmembrane loop region (7TM).

PMID- 15962317
TI  - Male cell microchimerism in normal and diseased female livers from fetal life to
      adulthood.
AB  - Male microchimerism is frequent in the adult female liver and is attributed to
      fetal cells originating from previous male offspring. It has never been studied
      in pregnant women, female children, or fetuses. We examined its frequency and
      cellular nature in normal and diseased female livers from fetal life to
      adulthood. Forty-six liver samples from 29 women, 6 female children, and 11
      female fetuses were screened for the Y chromosome via polymerase chain reaction
      (PCR) assay and fluorescent in situ hybridization (FISH). The X chromosome was
      used as an internal control. A third PCR assay was used for Y genotyping. The Y
      chromosome was detected in 5 of 6 children, 7 of 11 fetuses, 3 of 9 women with
      normal liver, 7 of 10 women with chronic hepatitis C, 5 of 6 women with acute
      liver disease during pregnancy with male offspring, and 2 of 4 nonpregnant women
      with fulminant hepatitis. In positive samples, the mean XY/XX ratio was 0.012 (+/
      0.004). In women, male microchimerism was correlated with previous male
      offspring. Male hepatocytes, detected via FISH combined with anti-hepatocyte
      immunohistochemistry, were observed only in fetuses (4/9) and in postpartem women
      (4/6). Y genotypes were different from each other in 4 of 5 female livers. In
      conclusion, male liver microchimerism is frequent in normal and diseased female
      livers. The presence of male cells in the liver of female children and fetuses is
      probably due to the transplacental transmission of fetal cells preexisting in the
      mother and acquired either from previous pregnancy with male offspring or during
      the mother's own fetal life.

PMID- 15962316
TI  - A20 protects mice from lethal radical hepatectomy by promoting hepatocyte
      proliferation via a p21waf1-dependent mechanism.
AB  - The liver has a remarkable regenerative capacity, allowing recovery following
      injury. Regeneration after injury is contingent on maintenance of healthy
      residual liver mass, otherwise fulminant hepatic failure (FHF) may arise.
      Understanding the protective mechanisms safeguarding hepatocytes and promoting
      their proliferation is critical for devising therapeutic strategies for FHF. We
      demonstrate that A20 is part of the physiological response of hepatocytes to
      injury. In particular, A20 is significantly upregulated in the liver following
      partial hepatectomy. A20 protects hepatocytes from apoptosis and ongoing
      inflammation by inhibiting NF-kappaB. Hepatic expression of A20 in BALB/c mice
      dramatically improves survival following extended and radical lethal hepatectomy.
      A20 expression in the liver limits hepatocellular damage hence maintains
      bilirubin clearance and the liver synthetic function. In addition, A20 confers a
      proliferative advantage to hepatocytes via decreased expression of the cyclin
      dependent kinase inhibitor p21(waf1). In conclusion, A20 provides a proliferative
      advantage to hepatocytes. By combining anti-inflammatory, antiapoptotic and pro
      proliferative functions, A20-based therapies could be beneficial in prevention
      and treatment of FHF.

PMID- 15962318
TI  - Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a
      highly standardized murine model.
AB  - Mortality in colorectal cancer is associated with the development of liver
      metastases. Surgical removal of these tumors is the only hope for cure, but
      recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often
      occurs as a result of hemorrhage or vascular clamping. Although the adverse
      effects of I/R on postoperative liver function are well documented, the influence
      of I/R on the outgrowth of residual micrometastases is unknown. We used a highly
      standardized mouse model of partial hepatic I/R to study the effects of I/R on
      the outgrowth of preestablished colorectal micrometastases. Five days following
      intrasplenic injection of C26 colon carcinoma cells, the vascular structures of
      the left lobe were clamped for 45 minutes under hemodynamically stable
      conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis,
      and tumor growth were assessed over time. I/R caused oxidative stress and early
      liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was
      accelerated five- to sixfold compared with nonoccluded lobes and was associated
      with areas of necrotic liver tissue surrounded by inflammatory cells and
      apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were
      completely prevented by occluding blood flow intermittently. In contrast,
      ischemic preconditioning or treatment with the antioxidants alpha-tocopherol or
      ascorbic acid failed to protect against late tissue necrosis and tumor growth,
      although early hepatocellular damage was largely prevented by these methods. In
      conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth.
      Measures to prevent I/R-induced late tissue necrosis cross-protect against this
      phenomenon.

PMID- 15962320
TI  - Steatosis: co-factor in other liver diseases.
AB  - The prevalence of fatty liver is rising in association with the global increase
      in obesity and type 2 diabetes. In the past, simple steatosis was regarded as
      benign, but the presence of another liver disease may provide a synergistic
      combination of steatosis, cellular adaptation, and oxidative damage that
      aggravates liver injury. In this review, a major focus is on the role of
      steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms
      promoting fibrosis and the effect of weight reduction in minimizing liver injury
      have been most widely studied. Steatosis, obesity, and associated metabolic
      factors may also modulate the response to alcohol- and drug-induced liver disease
      and may be risk factors for the development of hepatocellular cancer. The
      pathogenesis of injury in obesity-related fatty liver disease involves a number
      of pathways, which are currently under investigation. Enhanced oxidative stress,
      increased susceptibility to apoptosis, and a dysregulated response to cellular
      injury have been implicated, and other components of the metabolic syndrome such
      as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also
      may be increased as a by-product of altered hepatocyte regeneration and
      activation of bipotential hepatic progenitor cells. In conclusion, active
      management of obesity and a reduction in steatosis may improve liver injury and
      decrease the progression of fibrosis.

PMID- 15962321
TI  - Milk thistle and chronic liver disease.

PMID- 15962322
TI  - Diagnosis of small hepatocellular carcinoma.

PMID- 15962323
TI  - Of mice and women: toward a mouse model of autoimmune hepatitis.

PMID- 15962324
TI  - A novel target of hepatitis B virus mutations: splicing of surface RNA.

PMID- 15962325
TI  - Methodological issues and the measurement of fatigue in primary biliary
      cirrhosis.

PMID- 15962327
TI  - Inactivation of stress protein p8 increases murine carbon tetrachloride
      hepatotoxicity via preserved CYP2E1 activity.
AB  - The p8 protein is a transcription factor that regulates the expression of genes
      involved in cell defense against the adverse effects of stress. Its expression is
      strongly, rapidly, and transiently induced in most cells on exposure to various
      stress agents. This study assessed the role of p8 in the response of the liver to
      CCl(4)-induced injury. We found that p8 was indeed overexpressed in the liver
      after CCl(4) administration. Hepatic injury following CCl(4) injection was
      monitored in wild-type and p8(-/-) mice. Serum alanine and aspartate
      aminotransferase activities were higher and peaked earlier in p8(-/-) mice than
      in wild-type mice, which is in agreement with the observation of significantly
      larger areas of necrosis in p8(-/-) liver. Absence of p8 expression is therefore
      associated with increased liver sensitivity to CCl(4). In fact, CCl(4) toxicity
      is mediated by derivatives generated by its conversion by the enzyme CYP2E1. It
      is known that CYP2E1 is downregulated in the liver during the first hours
      following CCl(4) administration as part of a self-defense mechanism. We found
      that CYP2E1 downregulation was significantly delayed in p8(-/-) liver compared
      with wild-type liver, allowing increased production of toxic CCl(4) derivatives.
      In conclusion, inactivation of the p8 gene increases liver sensitivity to CCl(4),
      as it appears to delay the triggering of CYP2E1 downregulation. The p8 protein is
      therefore an important element of hepatocyte stress response.

PMID- 15962328
TI  - Transforming growth factor beta can mediate apoptosis via the expression of TRAIL
      in human hepatoma cells.
AB  - Transforming growth factor beta (TGF-beta) has been shown to induce apoptotic
      cell death in normal and transformed hepatocytes. However, the exact mechanism
      through which TGF-beta induces cell death is still unknown. We examined a
      potential role of various death receptor/ligand systems in TGF-beta-induced
      apoptosis and identified the tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) as a mediator of TGF-beta-induced apoptosis in hepatoma cells. TGF
      beta-induced apoptosis is significantly impaired upon blockage of TRAIL. We show
      that TRAIL is upregulated in hepatoma cells upon treatment with TGF-beta, whereas
      TRAIL receptor levels remain unchanged. In conclusion, our results provide
      evidence that the TRAIL system is critically involved in TGF-beta-induced cell
      death in liver pathology.

PMID- 15962329
TI  - Characterization of serine/cysteine protease inhibitor alpha1-antitripsin from
      meconium-instilled rabbit lungs.
AB  - We have recently purified from meconium-instilled rabbit lungs a novel serine
      proteinase inhibitor, with an apparent molecular mass of 50 kDa, which we assign
      to be alpha1-antitripsin. We hypothesize that serpin may attenuate pulmonary
      inflammation and improve surfactant function after meconium aspiration. Alpha1
      antitripsin is a member of the proteinase inhibitor (serpin) superfamily and
      inhibitor of neutrophil elastase, and it can be identified as a member of the
      family by its amino acid sequence due to the high degree of conserved residues.
      Alpha1-antitripsin is synthesized by epithelial cells, macrophages, monocytes,
      and neutrophils. Deficiency in alpha1-antitripsin leads to exposure of lungs to
      uncontrolled proteolytic attack from neutrophil elastase or other damaging
      factors culminating in lung destruction and cell apoptosis. We hypothesize that
      accumulation of alpha1-antitripsin in the lungs serves as a predisposed
      protection against meconium-induced lung injury. In this paper, we show how this
      knowledge can lead to the development of novel therapeutic approaches for
      treatment of MAS.

PMID- 15962331
TI  - Cytoplasmic retention of peroxide-activated ERK provides survival in primary
      cultures of rat hepatocytes.
AB  - Reactive oxygen species (ROS) are implicated in tissue damage causing primary
      hepatic dysfunction following ischemia/reperfusion injury and during inflammatory
      liver diseases. A potential role of extracellular signal-regulated kinase (ERK)
      as a mediator of survival signals during oxidative stress was investigated in
      primary cultures of hepatocytes exposed to ROS. Hydrogen peroxide (H(2)O(2))
      induced a dose-dependent activation of ERK, which was dependent on MEK
      activation. The ERK activation pattern was transient compared with the ERK
      activation seen after stimulation with epidermal growth factor (EGF). Nuclear
      accumulation of ERK was found after EGF stimulation, but not after H(2)O(2)
      exposure. A slow import/rapid export mechanism was excluded through the use of
      leptomycin B, an inhibitor of nuclear export sequence-dependent nuclear export.
      Reduced survival of hepatocytes during ROS exposure was observed when ERK
      activation was inhibited. Ribosomal S6 kinase (RSK), a cytoplasmic ERK substrate
      involved in cell survival, was activated and located in the nucleus of H(2)O(2)
      exposed hepatocytes. The activation was abolished when ERK was inhibited with
      U0126. In conclusion, our results indicate that activity of ERK in the cytoplasm
      is important for survival during oxidative stress in hepatocytes and that RSK is
      activated downstream of ERK. Supplementary material for this article can be found
      on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270
      9139/suppmat/index.html).

PMID- 15962332
TI  - Exercise training in mitochondrial myopathy: a randomized controlled trial.
AB  - Patients with mitochondrial myopathies (MM) usually suffer from exercise
      intolerance due to their impaired oxidative capacity and physical deconditioning.
      We evaluated the effects of a 12-week supervised randomized rehabilitation
      program involving endurance training in patients with MM. Twenty MM patients were
      assigned to a training or control group. For three nonconsecutive days each week,
      patients combined cycle exercise at 70% of their peak work rate with three upper
      body weight-lifting exercises performed at 50% of maximum capacity. Training
      increased maximal oxygen uptake (28.5%), work output (15.5%), and minute
      ventilation (40%), endurance performance (62%), walking distance in shuttle
      walking test (+95 m), and peripheral muscle strength (32%-62%), and improved
      Nottingham Health Profile scores (21.47%) and clinical symptoms. Control MM
      patients did not change from baseline. Results show that our exercise program is
      an adequate training strategy for patients with mitochondrial myopathy.

PMID- 15962330
TI  - Nicotine inhibits myofibroblast differentiation in human gingival fibroblasts.
AB  - Cigarette smoking has been suggested as a risk factor for several periodontal
      diseases. It has also been found that smokers respond less favorably than non
      smokers to periodontal therapy. Previous work in our lab has shown that nicotine
      inhibits human gingival cell migration. Since myofibroblasts play an important
      role in wound closure, we asked if nicotine affects gingival wound healing
      process by regulating myofibroblast differentiation. Human gingival fibroblasts
      (HGFs) from two patients were cultured in 10% fetal bovine serum cell culture
      medium. Cells were pretreated with different doses of nicotine (0, 0.01, 0.1, and
      1 mM) for 2 h, and then incubated with transforming growth factor beta (TGF
      beta1) (0, 0.25, 0.5, and 1 ng/ml) with or without nicotine for 30 h. The
      expression level of alpha-smooth muscle actin (alpha-SMA), a specific marker for
      myofibroblasts, was analyzed by Western blots, immunocytochemistry, and real-time
      polymerase chain reaction (real-time PCR). Phosphorylated p38 mitogen-activated
      protein kinase (Phospho-p38 MAPK) activity was analyzed by Western blots. TGF
      beta1 induced an increase of alpha-SMA protein and mRNA expression, while
      nicotine (1 mM) inhibited the TGF-beta1-induced expression of alpha-SMA but not
      beta-actin. Nicotine treatment down-regulated TGF-beta1-induced p38 MAPK
      phosphorylation. Our results demonstrated for the first time that nicotine
      inhibits myofibroblast differentiation in human gingival fibroblasts in vitro;
      supporting the hypothesis that delayed wound healing in smokers may be due to
      decreased wound contraction by myofibroblasts.

PMID- 15962333
TI  - Activity-dependent influences are greater for fibers in rat medial gastrocnemius
      than tibialis anterior muscle.
AB  - Skeletal muscles are highly adaptive to changes in loading or activation. A model
      of neuromuscular inactivity (spinal cord isolation, SI) was used to determine the
      role of activity-independent and -dependent neural influences on the size and
      myonuclei number in type-identified fibers of a fast extensor (medial
      gastrocnemius, MG) and flexor (tibialis anterior, TA) rat muscle. Fibers were
      categorized based on myosin heavy chain isoform composition. Four days after SI,
      all fiber types tended to atrophy and lose myonuclei, with the percent loss of
      myonuclei being disproportionately less than the decrease in fiber size. At 60
      days after SI, all fiber types in MG and the fastest fibers in TA were
      significantly smaller and had fewer myonuclei than control. The disproportionate
      amount of atrophy resulted in a smaller myonuclear domain. These effects were
      greater in MG than TA, indicating that activity-dependent influences were greater
      in the extensor than flexor. The smaller myonuclear domains after a period of
      chronic inactivity suggest the presence of intrinsic mechanisms operating to
      maintain the genetic material necessary to recover from atrophic conditions.

PMID- 15962334
TI  - Heat shock proteins and neuromuscular disease.
AB  - The heat shock proteins are families of proteins with known activities that
      include chaperoning nascent peptides within the cell and cytoprotection. Most
      work on the nervous system has related to the role of heat shock proteins in
      neuroprotection from either hypoxic-ischemic or traumatic injury. The role of
      these proteins during normal physiological activity and injury is still under
      investigation. Heat shock proteins in neuromuscular disease have been
      investigated to some extent but were largely neglected until recently. The goal
      of this review is to summarize the evidence linking heat shock proteins with
      neuromuscular disease and to provide some insight into the roles or functions of
      these proteins in disease states.

PMID- 15962335
TI  - Variations in gene expression among different types of human skeletal muscle.
AB  - There is a consistent variation in the response of different skeletal muscle
      groups to mutations in genes known to cause muscular dystrophy, yet these muscles
      appear histologically similar. To better understand these phenotypic differences,
      we analyzed gene expression patterns in control muscle specimens obtained from
      four sites at autopsy: deltoid, quadriceps, gastrocnemius, and tibialis anterior
      (TA). A total of 35 muscle samples from nine individuals (four pediatric and five
      geriatric) were studied. Factors potentially influencing gene expression in the
      different samples included individuality, age, muscle type, gender, cause of
      death, postmortem interval, and ethnicity. The first three factors, in decreasing
      order, were found to have a significant impact on the stratification of muscle
      specimens. A novel analytic method, using a second round of normalization, was
      used to elicit differences between muscle types. This approach may be extended to
      a broader survey, potentially elucidating a molecular classification of the
      skeletal muscles.

PMID- 15962336
TI  - How reliable are thermodynamic feasibility statements of biochemical pathways?
AB  - The driving force for organo- or lithotrophic growth as well as for each step in
      the metabolic network is the Gibbs reaction energy. For each enzymatic step it
      must be negative. Thermodynamics contributes therefore to the in-silico
      description of living systems. It may be used for assessing the feasibility of a
      given pathway because it provides a further constraint for those pathways which
      are feasible from the point of view of mass balance calculations (metabolic flux
      analysis) and the genetic potential of an organism. However, when this constraint
      was applied to lactic acid fermentation according to a method proposed by
      Mavrovouniotis (1993a, ISMB 93:273-283) it turned out that an unrealistically
      wide metabolite concentration range had to be assumed to make this well-known
      glycolytic pathway thermodynamically feasible. During a search for the reasons of
      this surprising result the insufficient consideration of the activity
      coefficients was identified as main cause. However, it is shown in the present
      contribution that the influence of the activity coefficients on Gibbs reaction
      energy can be easily taken into account based on the intracellular ionic
      strength. The uncertainty of the tabulated equilibrium constants and of the
      apparent standard Gibbs energies derived from them was found to be the second
      most important reason for the erroneous result of the feasibility analysis.
      Deviations of intracellular pH from the standard value and bad estimations of
      currency metabolites, e.g., NAD(+) and NADH, were found to be of lesser
      importance but not negligible. The pH dependency of Gibbs reaction enthalpy was
      proved to be easily taken into account. Therefore, the application of
      thermodynamics for a better in-silico prediction of the behavior of living cell
      factories calls predominantly for better equilibrium data determined under well
      defined conditions and also for a more detailed knowledge about the intracellular
      ionic strength and pH value.

PMID- 15962337
TI  - In silico design and adaptive evolution of Escherichia coli for production of
      lactic acid.
AB  - The development and validation of new methods to help direct rational strain
      design for metabolite overproduction remains an important problem in metabolic
      engineering. Here we show that computationally predicted E. coli strain designs,
      calculated from a genome-scale metabolic model, can lead to successful production
      strains and that adaptive evolution of the engineered strains can lead to
      improved production capabilities. Three strain designs for lactate production
      were implemented yielding a total of 11 evolved production strains that were used
      to demonstrate the utility of this integrated approach. Strains grown on 2 g/L
      glucose at 37 degrees C showed lactate titers ranging from 0.87 to 1.75 g/L and
      secretion rates that were directly coupled to growth rates.

PMID- 15962338
TI  - Evaluation of the tetracycline promoter system for regulated gene expression in
      Kluyveromyces marxianus.
AB  - A tetracycline repressible promoter system designed for Saccharomyces cerevisiae
      was evaluated for use in Kluyveromyces marxianus. A plasmid was constructed
      containing the Escherichia coli beta-glucuronidase (gus) gene cloned downstream
      of the yeast tet-off promoter, the tetR-VP16 activator protein gene, and the URA3
      gene for selection. The tet-off promoter-gus construct was integrated into the
      chromosomal DNA and tested under varying growth conditions in complex medium. The
      repressors tetracycline and doxycycline were both found to be effective for
      inhibiting gene expression. Doxycycline levels of 0.5 microg/mL or greater were
      sufficient to nearly completely suppress Gus synthesis. For most transformants,
      the induction ratio was approximately 2,000-fold. The tet-off promoter was
      effective at 30, 37, and 42 degrees C, although the overall Gus activity was
      highest at 37 degrees C. During exponential growth, little product was formed;
      expression increased dramatically in late exponential and early stationary phase.
      The promoter thus shows promise for protein synthesis following cell growth. No
      inducer is required and the repressor is only needed to prevent expression during
      the seed culture.

PMID- 15962339
TI  - Mutual relationships between soils and biological carrier systems.
AB  - Improved viability and antagonistic activity of biocontrol agents during soil
      inoculation is of crucial importance to their effective application. The
      chitinolytic bacterium Serratia marcescens was used as a model organism to study
      the efficacy of freeze-dried alginate beads (in comparison to their non-dried
      counterparts) as possible carriers for immobilized biocontrol agents. The release
      of bacteria and chitinolytic enzyme from alginate beads, before and during their
      application in soil, was examined, and the beads' physical properties
      characterized. Dispersal of the alginate bead-entrapped S. marcescens in the soil
      resulted in high soil cell densities throughout the 35 days of the experiment.
      Chitin inclusion in the beads resulted in significantly higher chitinolytic
      activity of S. marcescens, increased dry-bead porosity and decreased stiffness.
      Rehydration of the dried beads (after immersion in soil) resulted in a sixfold
      increase in weight due to water absorption. No significant differences were found
      in bacterial count inside the non-dried (gel) versus dried beads. However, higher
      cell densities and chitinase activity were detected in soil containing dried
      beads with chitin than in that containing their non-dried counterparts. The
      biological performance of S. marcescens was examined in the greenhouse: a free
      cell suspension reduced bean (Phaseolus vulgaris L.) disease by 10%, while
      immobilized bacteria found in the dried, chitin-containing beads reduced disease
      by 60%.

PMID- 15962340
TI  - Effect of pH change on the performance and microbial community of enhanced
      biological phosphate removal process.
AB  - An acetate-rich wastewater, containing 170 mg/L of total organic carbon (TOC), 13
      mg/L of N, and 15 mg/L of P, was treated using the enhanced biological phosphate
      removal (EBPR) process operated in a sequencing batch reactor. A slight change of
      pH of the mixed liquor from 7.0 to 6.5 led to a complete loss of phosphate
      removing capability and a drastic change of microbial populations. The process
      steadily removed 94% of TOC and 99.9% of P from the wastewater at pH 7.0, but
      only 93% TOC and 17% of P 14 days after the pH was lowered to pH 6.5. The sludge
      contained 8.8% P at pH 7.0, but only 1.9% at pH 6.5. Based on 16S rDNA analysis,
      64.8% of the clones obtained from the sludge at pH 7.0 were absent in the pH 6.5
      sludge. The missing microbes, some of which were likely responsible for the
      phosphate removal at pH 7.0, included beta-Proteobacteria, Actinobacteria,
      Bacteriodetes/Chlorobi group, plus photosynthetic bacteria and Defluvicoccus of
      the alpha-Proteobacteria. Among them, the last two groups, which represented 9.3%
      and 10.1% of the EBPR sludge at pH 7.0, have rarely been reported in an EBPR
      system.

PMID- 15962341
TI  - Copper(II) and zinc(II) complexes can fix atmospheric carbon dioxide.

PMID- 15962346
TI  - Effects of methoxyfenozide on Lobesia botrana Den & Schiff (Lepidoptera:
      Tortricidae) egg, larval and adult stages.
AB  - The effect of the non-steroidal ecdysone agonist methoxyfenozide was evaluated
      against different developmental stages of the grape berry moth, Lobesia botrana
      Dennis & Schiffermuller (Lep, Tortricidae). Methoxyfenozide administered orally
      reduced the fecundity and fertility of adults treated with 1, 5 and 10 mg litre(
      1); longevity was not affected. An LC(50) value of 4.5 mg litre(-1) was obtained
      when applied to eggs of less than 1 day old. Surface treatment was more effective
      than when applied by spraying. Administered into the diet, methoxyfenozide had a
      larvicidal effect; older larvae were more susceptible than younger larvae, with
      LC(50) values of 0.1 mg litre(-1) for L(1), 0.04 for L(3) and 0.02 for L(5).
      Larvae treated with sub-lethal doses throughout their lives did not emerge as
      adults at the highest doses (0.08, 0.04, 0.02 and 0.01 mg litre(-1)), with 65%
      and 40% emergence occurring for the lowest (0.005 and 0.0025 mg litre(-1)).
      Mortality occurred only in the larval stage.

PMID- 15962347
TI  - Chiral quantification of D-, L-phenylglycine mixture using mass spectrometric
      kinetic method.
AB  - A novel mass spectrometric method is applied to rapid, accurate, quantitative
      analysis of chiral phenylglycine. Transition-metal-bound complex ions containing
      the chiral phenylglycine are generated by electrospray ionization mass
      spectrometry and subjected to collision-induced dissociation. The ratio of the
      two competitive dissociation rates is related to the enantiomeric composition of
      the mixture, allowing the determination of enantiomeric contamination in the
      intermediates.

PMID- 15962348
TI  - Hydrophilic interaction liquid chromatography/mass spectrometry for determination
      of domoic acid in Adriatic shellfish.
AB  - This paper describes a new method for sensitive, specific and direct
      determination of domoic acid (DA), the causative toxin of amnesic shellfish
      poisoning (ASP) syndrome, in shellfish. It is based on combination of hydrophilic
      interaction liquid chromatography with mass spectrometry (HILIC/MS). The high
      percentage of organic modifier in the mobile phase and the omission of ion
      pairing reagents, both favoured in HILIC, result in enhanced detection limits
      with MS detection. The new method was set up either on an ionspray ion trap MS
      instrument operating in MS and MS/MS scanning acquisition modes, or on a
      turboionspray triple-quadrupole MS system operating in selected ion monitoring
      (SIM) and multiple reaction monitoring (MRM) acquisition modes. Positive and
      negative ion experiments were performed. MRM experiments are recommended for
      screening contaminated shellfish tissue and for quantitative analyses due to
      highest sensitivity and selectivity. The minimum detection levels for the toxin
      in tissue were found to be 63 and 190 ng/g in positive and negative MRM
      experiments, respectively, which are well below the regulatory limit for DA in
      tissue (20 microg/g). Application to shellfish samples collected in the Adriatic
      Sea (Italy) in the period 2000-2004 demonstrated for the first time in Italy the
      presence of DA as a new toxin that has entered the Adriatic Mytilus
      galloprovincialis toxin profile.

PMID- 15962349
TI  - Frontiers in GPCR research.

PMID- 15962350
TI  - Effects of chlorpyrifos in freshwater model ecosystems: the influence of
      experimental conditions on ecotoxicological thresholds.
AB  - Three experiments were conducted to determine the impact of the insecticide
      chlorpyrifos (single applications of 0.01 to 10 microg AI litre(-1)) in plankton
      dominated nutrient-rich microcosms. The microcosms (water volume approximately 14
      litres) were established in the laboratory under temperature, light regimes and
      nutrient levels that simulated cool 'temperate' and warm 'Mediterranean'
      environmental conditions. The fate of chlorpyrifos in the water column was
      monitored and the effects on zooplankton, phytoplankton and community metabolism
      were followed for 4 or 5 weeks. The mean half-life (t1/2) of chlorpyrifos in the
      water of the test systems was 45 h under 'temperate' conditions and about 30 h
      under 'Mediterranean' environmental conditions. Microcrustaceans (cladocerans and
      copepod nauplii) were amongst the most sensitive organisms. All three experiments
      yielded community NOEC (no observed effect concentrations) of 0.1 microg AI
      litre(-1), similar to those derived from more complex outdoor studies. Above this
      threshold level, responses and effect chains, and time spans for recovery,
      differed between the experiments. For example, algal blooms as an indirect effect
      from the impact of exposure on grazing organisms were only observed under the
      'Mediterranean' experimental conditions. The relatively simple indoor test system
      seems to be sufficient to provide estimates of safe threshold levels for the
      acute insecticidal effects of low-persistence compounds such as chlorpyrifos. The
      robustness of the community NOEC indicates that this threshold level is likely to
      be representative for many freshwater systems.

PMID- 15962351
TI  - Odysseus syndrome: nihilism by proxy (Connelly et al., 2005).

PMID- 15962352
TI  - Depression and anxiety in primary caregivers: a comparative study of caregivers
      of demented and nondemented older persons.

PMID- 15962353
TI  - An audit of the Addenbrooke's Cognitive Examination (ACE) in clinical practice.

PMID- 15962354
TI  - Postoperative delirium after elective orthopedic surgery.

PMID- 15962356
TI  - Triple quadrupole tandem mass spectrometry of sesquiterpene lactones: a study of
      goyazensolide and its congeners.
AB  - Electrospray ionization tandem mass spectrometry (ESI-MS/MS) was used to
      investigate the fragmentation pattern of ten sesquiterpene lactones of the
      goyazensolide type under low-energy collision-induced dissociation (CID) using a
      triple quadrupole mass spectrometer. The analysis revealed that loss of CO(2)[M +
      H - 44](+) is the predominant process for compounds that exhibit a hydroxyl at C
      8. In contrast, compounds with different acyloxy groups at C-8 fragment by means
      of elimination of the corresponding carboxylic acids [M + H - (R(2)CO(2)H)](+)
      and consecutive losses of CO and H(2)O. Our results also demonstrate the
      influence of both the stereochemistry of the acyloxy group at C-8 on the relative
      abundances of product ions and the hydroxyl at C-15, which creates an additional
      pathway, resulting in highly diagnostic product ions. This work clearly
      demonstrates the utility of tandem quadrupole low-resolution mass spectrometry
      for studies on the rationalization of the fragmentation of a series of compounds
      with a highly conserved core structure, but differing in substituent groups.

PMID- 15962357
TI  - Effect of stereochemistry on the electrospray ionization tandem mass spectra of
      transition metal chloride complexes of monosaccharides.
AB  - The effect of stereochemistry on the complexation of aldohexoses (glucose,
      mannose, galactose, allose and talose) and ketohexoses (fructose, tagitose and
      sorbose) with transition metal chlorides (CoCl(2), NiCl(2), MnCl(2) and ZnCl(2))
      has been investigated by electrospray ionization tandem mass spectrometry.
      Electrospray ionization of methanolic solutions of hexoses containing metal
      chlorides gave abundant ions corresponding to [M + MetCl](+) and [2M + MetCl](+)
      which on collision-induced dissociation gave characteristic fragment ions. The
      fragmentation pathways have been confirmed by examining methyl glucoside and
      several isotopically labeled glucoses. Eliminations of H(2)O and HCl, C-C
      cleavages and elimination of metalhydroxychloride are the competing fragmentation
      pathways observed. All these pathways seem to be influenced by the
      stereochemistry of the molecule. The fragmentation of the dimeric complexes, [2M
      + MetCl](+), is also controlled by the stereochemistry of the molecule. The
      abundance of the product ions corresponding to elimination of HCl is found to
      increase with increasing number of axial hydroxyl groups in aldohexoses. [2M +
      MetCl](+) dissociates by elimination of HCl followed by C(2)H(4)O(2) in
      aldohexose complexes and by elimination of HCl followed by C(3)H(6)O(3) in
      ketohexose complexes.

PMID- 15962358
TI  - Characterisation of sulphoxides by atmospheric pressure ionisation mass
      spectrometry.
AB  - An observation that a series of proprietary compounds containing a methyl
      thiophenyl group all underwent metabolic S-oxidation, and that the product ion
      spectra of the resulting S-oxides showed methyl radical loss under low-energy
      atmospheric pressure ionisation tandem mass spectrometry (API-MS/MS) conditions,
      has led to an investigation of the fragmentation of commercially available
      sulphoxides. The phenyl methyl sulphoxides studied do lose methyl radicals under
      MS/MS conditions on triple quadrupole mass spectrometers. In addition, the phenyl
      sulphoxides, with simple substituents other than a methyl group, also showed a
      tendency to lose the substituent as a radical. It was concluded that radical loss
      from these simple sulphoxides was characteristic of S-oxidation of these
      molecules. Radical losses, such as those reported here, are used in-house to
      distinguish S-oxidation from N- and C-oxidation in metabolism studies.

PMID- 15962359
TI  - A shot in the arm for immunotherapy.

PMID- 15962360
TI  - Benzidine photodegradation: a mass spectrometry and UV spectroscopy combined
      study.
AB  - The benzidine photodegradation process was studied using UV/Vis spectroscopy and
      electrospray ionization mass spectrometry (ESI-MS) combined with collision
      induced dissociation (CID) and tandem mass spectrometry (MS/MS). Mass
      spectrometry was used to characterize benzidine and to identify and characterize
      possible degradation products and intermediates. The MS data showed that
      benzidine is quite persistent in aqueous medium. Moreover, the MS analysis
      enabled us to propose the following three degradation products/intermediates: 4'
      nitro-4-biphenylamine, tetrahydroxybiphenyl and 4,4'-dinitrobiphenyl. For the
      benzidine molecular ion and protonated molecule and for the protonated molecules
      of the degradation products/intermediates detected, fragmentation patterns are
      proposed based on CID and MS/MS data. For the photodegradation process different
      catalysts were used, namely the commercial TiO2 Degussa P25, and the laboratory
      prepared ZnO, TiO2 anatase and a titanium-zinc oxide with a perovskite type
      structure. Comparison of the different catalysts showed that degradation was
      favoured with the commercial TiO2. Nevertheless, the other catalysts appear to be
      promising and economic alternatives for potential future remediation studies.

PMID- 15962361
TI  - Hepatitis B and alcohol affect survival of hepatocellular carcinoma patients.
AB  - AIM: In the USA, Hawaii has the highest incidence of hepatocellular carcinoma
      (HCC) and a diverse population. It is an ideal place to characterize HCC in the
      context of ethnicity/risk factors. METHODS: A total of 262 cases of HCC (1992
      2003) were retrospectively reviewed for demographics, ethnicity, birthplace,
      viral hepatitis, alcohol use, diabetes, smoking and risk factors for viral
      hepatitis such as intravenous drug abuse (IVDA), transfusions, tattoos and
      vertical transmission. Tumor stage, Child's class, Cancer of the Liver Italian
      Program (CLIP) score, alpha-fetoprotein level, treatment and survival were
      recorded. RESULTS: Gender, age, viral hepatitis, alcohol, IVDA, and diabetes
      differed significantly in Asians, non-Asians and Pacific Islanders. There were
      also specific differences within Asian subgroups. Alpha-fetoprotein, smoking,
      transfusions, stage and resectability did not differ between groups. Asians were
      more likely to have hepatitis B, while non-Asians were more likely to have
      hepatitis C. Factors that decreased survival included hepatitis B, alcohol,
      elevated alpha-fetoprotein, CLIP>2 and increased Child's class. When Asians were
      combined with Pacific Islanders, median survival (1.52 years vs 3.54 years), 1-
      and 3-year survival was significantly worse than those for non-Asians. After Cox
      regression analysis for hepatitis B and alcohol, there was no difference in
      survival by ethnicity. CONCLUSION: Various ethnicities have different risk
      factors for HCC. Hepatitis B, alcohol, and alpha-fetoprotein are more important
      factors for survival than ethnicity.

PMID- 15962362
TI  - Overexpression of Bax induces apoptosis and enhances drug sensitivity of
      hepatocellular cancer-9204 cells.
AB  - AIM: To investigate the role of overexpression of Bax in apoptotic pathways and
      the response of human hepatocellular cancer (HCC)-9204 cells to cell death
      induced by adriamycin. METHODS: The whole length of Bax cDNA was transfected into
      human HCC-9204 cells by the method of lipofectamine transfection. An inducible MT
      II regulatory system was constructed, which allowed controlled expression of
      protein upon addition of ZnSO4 (100 micromol/L) as an external inducer. Stable
      transfecting inducible expression vector containing Bax gene was performed.
      Expression of Bax in protein was analyzed by immunohistochemistry and Western
      blotting. TUNEL and flow cytometry were used to assess the effect of Bax on
      apoptosis. Colony assay and tetrazolium blue (MTT) assay were used to evaluate
      the difference in drug sensitivity of HCC-9204 cells after Bax-transfection.
      RESULTS: Immunohistochemistry and Western blotting demonstrated that the
      expression of Bax protein markedly increased in Bax-transfected cells 4 h after
      the addition of ZnSO4. Bax positive signal was frequently found on the cytoplasm
      and perinuclear region of HCC-9404 cells, and there was ectopic expression in
      cells with marked condensation of chromatin and cytoplasm (apoptotic cells).
      Apoptotic index significantly increased in Bax-transfected HCC-9204/Bax cells
      (3.6 vs 27.2, 4.2 vs 32.3, P<0.05). Flow cytometry analysis showed a significant
      sub-G1 peak and apoptosis in 15.4% HCC-9204/Bax cells 24 h after treatment.
      Furthermore, colony survival rate decreased from 66% (HCC-9204/pMD) to 45% (HCC
      9204/Bax) 2 d after ADR withdrawal. MTT assay result showed that the effects of
      Bax on cell viability following ADR exposure were significant as compared to the
      vehicle-transfected HCC-9204/pMD cells (21% vs 44%, P<0.01). CONCLUSION:
      Overexpression of Bax not only induces apoptosis, but also sensitizes HCC-9204
      cells to cell death induced by adriamycin.

PMID- 15962363
TI  - Effective inhibition of expression of hepatitis B virus genes by DNAzymes.
AB  - AIM: To evaluate the inhibitory effects of DNAzymes on the expressions of
      hepatitis B virus (HBV) s (HBsAg) and e (HBeAg) in 2.2.15 cells, and to explore
      the potential therapeutic effects of DNAzymes on replication of HBV genome.
      METHODS: DNAzymes DrzBS and DrzBC specific to HBV (ayw subtype) s gene ORF A157UG
      and e gene ORF A1816UG, were designed and synthesized. Inhibitory effects of
      DrzBS or DrzBC on the expressions of HBV s and e genes as well as HBV DNA levels
      in culture supernatants were observed in 2.2.15 cells. RESULTS: After being
      treated with DrzBS or DrzBC, the expression of HBV s or e genes in 2.2.15 cells
      was depressed dramatically. The maximum inhibition rate was 94.2% and 91.8% for
      DrzBS and DrzBC, respectively. The concentration for effective inhibition of both
      DrzBS and DrzBC was within 0.1-2.5 micromol/L, showing a dose-dependence. The
      efficiency of inhibiting HBsAg, HBeAg in 2.2.15 cells by DrzBS or DrzBC was
      higher than that of the same target genes by antisense oligonucleotides (ASON).
      The concentration for effective inhibition of DNAzymes was at least 10-fold lower
      compared with ASON controls. Neither inhibition on the replication of HBV DNA nor
      toxicity to 2.2.15 cells was observed. CONCLUSION: DrzBS and DrzBC can block the
      expression of HBV s- and e-genes in 2.2.15 cells and provide a specific and
      effective anti-HBV gene therapeutic means.

PMID- 15962364
TI  - Pancreatic involvement in chronic viral hepatitis.
AB  - AIM: To elucidate the frequency and characteristics of pancreatic disorders in
      the course of chronic viral hepatitis. METHODS: We prospectively assessed the
      serum pancreatic enzyme levels and imaging findings in patients with chronic
      viral hepatitis and healthy control subjects. RESULTS: Serum amylase (t-Amy),
      salivary amylase (s-Amy), pancreatic amylase (p-Amy) and serum lipase levels were
      higher in hepatitis patients in comparison to control subjects. However, in
      asymptomatic viral carriers, only the serum t-Amy levels were higher than those
      of the controls. The levels of each enzyme rose with the progression of liver
      disease in patients with hepatitis B or C; whereas the levels of each enzyme
      within the same clinical stage of the disease did not differ between patients
      diagnosed with either hepatitis B or hepatitis C virus. Imaging findings
      demonstrated chronic pancreatitis in only 1 out of 202 patients (0.5%).
      CONCLUSION: Our data suggest that serum levels of pancreatic enzymes increase
      with the progression of liver disease in patients diagnosed with viral hepatitis.
      Pancreatic disease, asymptomatic in most cases, may represent an extrahepatic
      manifestation of chronic viral hepatitis.

PMID- 15962365
TI  - Direct measurement of gastric H+/K+-ATPase activities in patients with or without
      Helicobacter pylori-associated chronic gastritis.
AB  - AIM: The role of Helicobacter pylori (H pylori) infection in gastric acid
      secretion of patients with chronic gastritis remains controversial. This study
      was designed to elucidate the effect of H pylori on H+/K+-ATPase activities in
      gastric biopsy specimens. METHODS: Eighty-two patients with chronic gastritis who
      had undergone upper endoscopy were included in this study. H pylori infection was
      confirmed by rapid urease test and histology. Gastric H+/K+-ATPase activities and
      serum gastrin concentrations were measured by an enzymatic method and
      radioimmunoassay, respectively. For those patients who received triple therapy
      for eradicating H pylori, changes in the activity of gastric H+/K+-ATPase and
      serum gastrin levels were also measured. RESULTS: The mean gastric H+/K+-ATPase
      activity in H pylori-positive group (42 patients) was slightly higher than that
      in H pylori-negative group (29 patients) (169.65+/-52.9 and 161.38+/-43.85 nmol
      Pi/(mg.h), respectively, P=0.301). After eradication of H pylori, the gastric
      H+/K+-ATPase activities slightly decreased compared to prior therapy (165.03+/
      59.50 and 158.42+/-38.93 nmol Pi/(mg.h), respectively, P=0.805). The mean basal
      gastrin concentration was slightly higher in H pylori-positive patients than in H
      pylori-negative patients (87.92+/-39.65 pg/mL vs 75.04+/-42.57 pg/mL, P=0.228).
      The gastrin levels fell significantly after the eradication of H pylori. (Before
      treatment 87.00+/-30.78 pg/mL, after treatment 64.73+/-18.96 pg/mL, P=0.015).
      CONCLUSION: Gastric H+/K+-ATPase activities are not associated with H pylori
      status in patients with chronic gastritis.

PMID- 15962366
TI  - Patients with Helicobacter pylori positive and negative duodenal ulcers have
      distinct clinical characteristics.
AB  - AIM: To assess the clinical characteristics of Helicobacter pylori (H pylori)
      negative duodenal ulcer. METHODS: Patients with an endoscopic diagnosis of
      duodenal ulcer between 1996 and 2002 were included in the present study. Patients
      were considered to be negative for H pylori, if both histological examination and
      rapid urease test of biopsy specimens were negative. A comparison was made
      between patients with H pylori positive and negative duodenal ulcers. RESULTS: A
      total of 1 343 patients were studied. Their mean age was 54.7+/-0.5 years. There
      was a male preponderance (M:F=2.5:1). Three hundred and ninety-eight patients
      (29.6%) did not have H pylori infection. The annual proportion of patients with H
      pylori negative duodenal ulcers increased progressively from 1996 to 2002. On
      multivariate analysis, patients with H pylori negative duodenal ulcer were more
      likely to be older, have concomitant medical problem, pre-existing malignancy,
      recent surgery, underlying sepsis, or taken non-steroidal anti-inflammatory
      drugs. In terms of clinical presentations, patients with H pylori negative
      duodenal ulcer were more likely to present with bleeding, multiple ulcers and
      larger ulcers. CONCLUSION: The proportion of patients with H pylori negative
      duodenal ulcers is on the rise because of a continued drop in incidence of H
      pylori positive duodenal ulcers in recent years. Such patients have distinct
      clinical characteristics and it is important to ascertain the H pylori status
      before starting eradication therapy.

PMID- 15962367
TI  - Distribution of Helicobacter pylori in north China.
AB  - AIM: To compare the distribution of virulence-associated genotypes of
      Helicobacter pylori (H pylori) in two areas of north China with different gastric
      cancer risk and furthermore probe into the pathogenicity of the bacterium.
      METHODS: Gastric biopsies were taken from 355 subjects from Zhuanghe, a high risk
      area of gastric cancer, and 136 subjects from Shenyang, a low risk area of
      gastric cancer. A total of 149 H pylori strains isolated from these patients were
      studied by PCR for differences in the genotypes of cagA, vacA, and iceA. RESULTS:
      In patients with high risk for gastric cancer, higher frequencies of vacA s1 or
      s1m1b genotypes were found as compared to those from the low risk area.
      CONCLUSION: There is significantly different distribution of H pylori genotypes
      between Zhuanghe and Shenyang areas in north China.

PMID- 15962368
TI  - Helicobacter pylori specific immune response induced by conservative flagellin
      linear B-cell epitope.
AB  - AIM: To testify the immunogenicity of a conservative B-cell linear epitope of
      Helicobacter pylori (H pylori) flagellin A. METHODS: Different programs were used
      to analyze the secondary structure, molecular hydropathy, and surface
      accessibility of H pylori flagellin A. Linear B-cell epitopes were estimated
      based on the structural and physiochemical information. Analysis of residue
      divergence was proposed to screen a conservative linear epitope. The 29-peptide
      (Pep29mer) synthesized by chemical method, including the predicted conservative B
      cell epitope and a known K2d compatible T-cell epitope, was used to immunize
      mice, and then H pylori-specific antibodies were detected by ELISA. RESULTS:
      Based on the analyses of divergent amino acid residues, structural and
      physiochemical characteristics, it was strongly suggested that the short fragment
      NDSDGR was the core of a conservative linear epitope in flagellin A. Animals
      immunized by Pep29mer acquired efficient immune response. In detail, serum H
      pylori-specific IgA and IgG1 increased significantly in immunized group, while
      IgG2a only had an insignificant change. H pylori-specific IgA in gastrointestinal
      flushing fluid also increased significantly. CONCLUSION: The conservative short
      fragment NDSDGR is the core of a linear B-cell epitope of flagellin A.

PMID- 15962370
TI  - Effects of Changtai granules, a traditional compound Chinese medicine, on chronic
      trinitrobenzene sulfonic acid-induced colitis in rats.
AB  - AIM: To study the effects of Changtai granules (CTG), a traditional compound
      Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in
      rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250
      300 g, were employed in the present study. The rat colitis models were induced by
      2,4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg
      in 50% ethanol. The experimental animals were randomly divided into dexamethasone
      (DX) treatment, CTG treatment, and model control groups, which were intracolicly
      treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude
      drug/kg, and the equal amount of saline respectively from 6 h following induction
      of the colitis in rats inflicted with TNBS to the end of study. A normal control
      group of rats treated without TNBS but saline enema was also included in the
      study. After 3 wk of treatment, the animals were assessed for colonal
      inflammatory and ulcerative responses with respect to mortality, frequency of
      diarrhea, histology and myeloperoxidase activity (MPO). RESULTS: The therapeutic
      effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively
      inhibited the activity of granulocytes, macrophages and monocytes in a dose
      dependent manner. Also it reduced MPO and formation of inflammation in colonic
      mucosal tissue. Furthermore, administration of CTG significantly prevented body
      mass loss and death, and decreased frequency of diarrhea in UC rats, when
      compared with the model control group rats. CONCLUSION: CTG would prove to be an
      ideal drug for chronic UC, and is warranted to be studied further.

PMID- 15962369
TI  - Glutamine is highly effective in preventing in vivo cobalt-induced oxidative
      stress in rat liver.
AB  - AIM: To evaluate the in vivo effect of glutamine on cobalt-generated oxidative
      stress and (HO-1) induction in rat liver. METHODS: Fasted female Wistar rats
      received a single injection of cobalt chloride (375 micromol/kg body weight) and
      then were killed at different times. Lipid peroxidation and soluble and enzymatic
      antioxidant defense system (reduced glutathione (GSH), catalase (CAT),
      glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) were measured in
      liver homogenates. Ferritin and ferritin iron contents as well as heme oxygenase
      1 (HO-1) activity and expression were also determined. The antioxidant properties
      of glutamine (Gln) were also evaluated. RESULTS: Cobalt chloride increased lipid
      peroxidation (50% over control values) 1 h after treatment. GSH reached a minimum
      at 3 h (40%) increasing thereafter. Twelve hours after CoCl2 injection, the
      antioxidant enzymes CAT, GSH-Px and SOD also diminished by about 30%. Heme
      oxygenase-1 induction was observed 6 h after treatment reaching a maximum value
      of 14-fold over the controls, 12 h after cobalt treatment. A 1.7-fold increase in
      ferritin and ferritin-bound iron 24 h after treatment were also obtained.
      Administration of glutamine (300 mg/kg body weight) by gavage 24 h before CoCl2
      treatment entirely prevented the increase in thiobarbituric acid reactive
      substances (TBARS) content, the decrease in GSH levels, and partially reverted
      heme oxygenase-1 induction. CONCLUSION: These results suggested that a natural
      product such as glutamine prevents glutathione depletion and consequently heme
      oxygenase induction.

PMID- 15962371
TI  - P-glycoprotein is not involved in pathway of anti-Fas/Fas-induced apoptosis in
      KBv200 cells.
AB  - AIM: To verify whether P-glycoprotein (P-gp) could induce cell resistance to
      apoptosis by inhibiting caspase-8 and caspase-3. METHODS: Human KB cells, either
      drug-sensitive or with multidrug resistance (MDR) phenotype caused by
      overexpression of P-gp (KBv200 cells), were treated with anti-Fas (CH-11
      monoclonal antibody) to induce apoptosis. Cytotoxicity was detected by MTT assay.
      Symptoms of cell death were assessed by morphological observation after
      Hoechst33258 staining, activation of caspase-8 and caspase-3 was measured by
      Western blotting. RESULTS: Compared with KB cells, the resistance of KBv200 cells
      to VCR (vincristine) was about 51-fold higher. Anti-Fas (CH-11) induced
      cytotoxicity and apoptosis in both sensitive KB cells and MDR phenotype KBv200
      cells. The IC50 of CH-11 in KB cells was similar to that in KBv200 cells. CH-11
      induced similar apoptotic rates in both KB cells and KBv200 cells, which could be
      classified as caspase-dependent apoptotic pathway. Verapamil (VRP) did not affect
      CH-11-mediated apoptosis in KBv200 cells. CONCLUSION: Expression of P
      glycoprotein does not induce resistance to caspase-8 and -3 activation or anti
      Fas-induced cell apoptosis.

PMID- 15962372
TI  - Effects of adrenomedullin gene overexpression on biological behavior of hepatic
      stellate cells.
AB  - AIM: To investigate the effects of adrenomedullin (AM) gene overexpression on the
      biological characteristics of human hepatic stellate cells (hHSCs) by stable
      transfection. METHODS: hHSCs which express low basal levels of AM were stably
      transfected with an expression construct containing rat AM gene or with an empty
      expression vector. Expression of AM in hHSCs was determined by reverse
      transcription (RT)-polymerase chain reaction (PCR) and radioimmunoassay (RIA).
      Cell proliferation was evaluated by 5-bromo-2'-deoxyuridine (BrdU) incorporation
      and immunocytochemistry. RT-PCR and Western blot were used to test the expression
      of procollagen types I and III. Protein expressions of interstitial collagenase
      (MMP-1), gelatinase (MMP-2) and tissue inhibitors of matrix metalloproteinases-2
      (TIMP-2) were assessed by Western blot. RESULTS: Two cell clones (A-2, A-8)
      transfected with the AM gene expressed higher levels of AM mRNA (non-transfected
      group: 0.86+/-0.11, empty vector group: 1.01+/-0.11, A-2 clone group: 1.44+/-0.08
      and A-8 clone group: 1.36+/-0.05) and protein (12.31+/-0.17, 12.35+/-0.12,
      12.56+/-0.06 and 12.62+/-0.07) (P<0.05). AM gene overexpression had inhibitory
      effects on cell proliferation of hHSCs (29.6%, 30.9%, 18.9% and 21.8%,
      respectively. P<0.05) and expression of procollagen type I (0.58+/-0.1, 0.48+/
      0.11, 0.3+/-0.06 and 0.31+/-0.07 at mRNA level) (0.27+/-0.07, 0.3+/-0.06, 0.14+/
      0.05 and 0.13+/-0.05 at protein level) (P<0.05) and procollagen type III (0.17+/
      0.04, 0.15+/-0.03, 0.1+/-0.02 and 0.09+/-0.02 at mRNA level) (0.22+/-0.04, 0.2+/
      0.03, 0.11+/-0.04 and 0.13+/-0.03 at protein level) (P<0.05). Compared with cells
      non-transfected (TIMP2: 2.77+/-0.03, MMP-2: 0.5+/-0.04, MMP-1: 0.49+/-0.07) and
      transfected with empty vector (TIMP2: 2.79+/-0.04, MMP-2: 0.48+/-0.03, MMP-1:
      0.45+/-0.09), these two clones had lower expression levels of TIMP2(A-2 clone
      group: 2.7+/-0.02 and A-8 clone group: 2.71+/-0.02) (P<0.05) and MMP-2(A-2 clone
      group: 0.15+/-0.05 and A-8 clone group: 0.13+/-0.04) (P<0.05) but displayed a
      higher expression level of MMP-1(A-2 clone group: 0.68+/-0.06 and A-8 clone
      group: 0.81+/-0.09) (P<0.05). CONCLUSION: AM gene exerts negative influence to
      some extent on hHSCs by inhibiting proliferation and production of extracellular
      matrix (ECM) in addition to inducing MMP-1 expression.

PMID- 15962373
TI  - Peroxynitrite induced decrease in Na+, K+-ATPase activity is restored by taurine.
AB  - AIM: Peroxynitrite (ONOO-) is a powerful oxidant shown to damage membranes. In
      the present study, the effect of taurine on changes of liver plasma membrane Na+,
      K+-ATPase induced by ONOO- was investigated. METHODS: Liver plasma membrane was
      exposed to ONOO- with or without taurine. Na+, K+-ATPase activity and lipid
      peroxidation as thiobarbituric acid reactive substances (TBARS) levels were
      measured. RESULTS: Different concentrations of ONOO- (100, 200, 500, and 1000
      micromol/L) were found to decrease liver plasma membrane Na+, K+-ATPase activity
      significantly. The depletion of enzyme activity was not concentration dependent.
      Effects of different concentrations of taurine on liver plasma membrane Na+, K+
      ATPase activity were also measured. Taurine did not cause any increase in enzyme
      activity. When plasma membranes were treated with 200 micromol/L ONOO- with
      different concentrations of taurine, a restoring effect of taurine on enzyme
      activity was observed. TBARS levels were also measured and taurine was found to
      decrease the elevated values. CONCLUSION: Taurine is observed to act as an
      antioxidant of ONOO- to decrease lipid peroxidation and thus affect liver plasma
      membrane Na+, K+-ATPase by restoring its activity.

PMID- 15962374
TI  - A comparison of the clinical, demographic and psychiatric profiles among patients
      with erosive and non-erosive reflux disease in a multi-ethnic Asian country.
AB  - AIM: To examine the clinical spectrum of gastroesophageal reflux disease (GERD)
      and compare erosive (ERD) with non-erosive (NERD) in terms of clinical,
      demographic and psychiatric profiles. METHODS: Patients with reflux symptoms were
      enrolled and stratified to NERD and ERD after endoscopy (LA classification).
      Patients with ERD presenting with dyspepsia were included. Patients on proton
      pump inhibitors (PPI) or H2 receptor antagonists before endoscopy were excluded.
      Demographic data, Helicobacter pylori (H pylori) status and presence of minor
      psychiatric morbidity (based on General Health Questionnaire-28) were analyzed.
      RESULTS: Among 690 patients screened, 533 were eligible for analysis (male to
      female ratio: 3:2; Chinese: 75.4%; Malay: 9.8%; Indian: 14.8%). Clinical spectrum
      of GERD: N: 40.5%; A: 46%; B: 9.2%; C: 2.1%; D: 0.6%; Barrett's esophagus: 1.7%.
      Compared to patients with NERD, patients with ERD were significantly older (45 vs
      39.4 years), more likely to be male (64.4% vs 53.7%), tended to smoke (19.6% vs
      9.7%), less likely to have minor psychiatric morbidity (26.4 vs 46.7%) and were
      more likely to respond to PPI (79.7 vs 66.8%). There was also a trend towards a
      higher BMI (24.5 vs 23.5). Race, alcohol consumption and H pylori status were not
      significant. On multivariate analysis, age and presence of minor psychiatric
      morbidity remained with significant differences. CONCLUSION: The majority of
      patients who have typical symptoms of GERD have NERD or mild erosive reflux
      disease. Compared to patients with erosive reflux disease, patients with NERD
      were younger and had a higher prevalence of minor psychiatric morbidity.

PMID- 15962375
TI  - Prevalence of non-Helicobacter pylori duodenal ulcer in Karachi, Pakistan.
AB  - AIM: To determine the prevalence of non-Helicobacter pylori (H pylori)-related
      duodenal ulcer in patients with acid-peptic diseases. METHODS: Medical records of
      patients who attended the Gastroenterology Department at Aga Khan University
      Hospital from 1999 to 2001 and had endoscopic diagnosis of duodenal ulcers were
      reviewed. Duodenal ulcer associated with H pylori was diagnosed on the basis of
      endoscopy, rapid urease test and histopathology whereas histories of aspirin or
      other non-steroidal anti-inflammatory drugs (NSAIDs) related duodenal ulcers. Non
      H pylori, non-NSAID duodenal ulcers were those without H pylori infection and
      history of NSAID intake. Co-morbid conditions associated were noted. RESULTS: Of
      2 260 patients, 10% (217/2 260) had duodenal ulcer. Duodenal ulcer related to H
      pylori infection accounted for 53% (116/217), NSAID-related 10% (22/217), non-H
      pylori non-NSAID 29% (62/217), and 8% (17/217) had both H pylori infection and
      histories of NSAID intake. Fifteen percent (18/116) patients had past histories
      of peptic ulcer disease in H pylori infection, while 8% (5/62) in non-H pylori
      non-NSAID ulcer. Co-morbid conditions in H pylori infection were seen in 23%
      (27/116) and 34% (21/62) in non-H pylori non-NSAID ulcer. CONCLUSION: Incidence
      of H pylori infection related with duodenal ulcer is common. In the presence of
      co-morbids, non-H pylori and non-NSAID duodenal ulcer is likely to be present.

PMID- 15962376
TI  - One-week dual therapy with ranitidine bismuth citrate and clarithromycin for the
      treatment of Helicobacter pylori infection in Brazilian patients with peptic
      ulcer.
AB  - AIM: To assess the efficacy and safety of ranitidine bismuth citrate plus
      clarithromycin given for 1 wk in Brazilian patients with peptic ulcer. METHODS:
      One hundred and twenty patients with peptic ulcer were randomized in two
      treatment groups: (1) 1-wk regimen consisting of ranitidine bismuth citrate 400
      mg b.i.d. with clarithromycin 500 mg b.i.d. or (2) 2-wk regimen of the same
      treatment. Eradication of the infection was considered when both the histologic
      examination and the urease test were negative for the infection 3 mo after
      treatment. RESULTS: By intention to treat analysis, Helicobacter pylori (H
      pylori) was eradicated in 73% and 76% of patients, respectively treated for 1 or
      2 wk (P>0.05). By per protocol analysis, the eradication rates were 80% and 83%,
      respectively, in patients treated for 1 or 2 wk (P>0.05). Nine patients (8.2%)
      reported minor side effects. CONCLUSION: One-week therapy with ranitidine bismuth
      citrate and clarithromycin is safe, well tolerated and effective for treatment of
      H pylori infection, and appears to be comparable to the 2-wk regimen in terms of
      efficacy.

PMID- 15962377
TI  - Oxidative stress in portal hypertension-induced rats with particular emphasis on
      nitric oxide and trace metals.
AB  - AIM: To investigate the oxidative-stress-related changes in rats with portal
      hypertension with particular emphasis on nitric oxide (NO) and trace metals.
      METHODS: Cirrhosis was induced by partial portal vein ligation (PVL) in Wistar
      rats. The lipid peroxidation marker (malondialdehyde, MDA), antioxidant defense
      enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH),
      and agents known to have antioxidant features including nitric oxide (NO), zinc
      (Zn), copper (Cu) were determined both in serum and in liver tissue at 4 wk after
      surgery in PVL and sham-operated rats. Portal pressure of all experimental
      animals was measured. MDA was detected by thiobarbituric acid reactivity assay.
      SOD activity was determined by inhibition of nitroblue tetrazolium reduction with
      xanthine/xanthine oxidase used as a superoxide generator. CAT activity was
      determined by the breakdown of hydrogen peroxide. GSH concentrations were
      measured by using metaphosphoric acid for protein precipitation and 5'-5'-dithio
      bis-2-nitrobenzoic acid for color development. NO was detected by the Griess
      method after reduction of nitrate to nitrite with nitrate reductase, and the
      concentrations of Zn and Cu were measured by a Shimadzu 680 AA atomic absorption
      spectrometer. Histopathological confirmation was done under light microscope.
      Statistical analyses were done by Student's t-test, and significance of the
      difference was tested by the unpaired Mann-Whitney test. P<0.05 was considered
      statistically significant. RESULTS: Histopathological studies confirmed PVL
      induced cirrhotic changes. There was a statistically significant difference in
      portal pressure between PVL and control groups (P<0.001). The results showed
      significant increases in the levels of MDA and NO in both tissue and serum
      (P<0.05 and P<0.001, respectively in tissue; P<0.001 for each in serum), and Zn
      only in tissue (P<0.001) in rats with PVL compared with sham-operated rats.
      Besides, PVL rats exhibited reduced plasma and tissue GSH, CAT, SOD (P<0.001 for
      each). Serum and tissue Cu concentration did not change. CONCLUSION: Our findings
      suggest that PVL in rats induces important biochemical and molecular changes
      related to oxidative stress in the liver.

PMID- 15962378
TI  - Dieulafoy's lesion: a case series study.
AB  - AIM: Dieulafoy's lesion (DL) accounts for 1-5.8% of cases of acute upper
      gastrointestinal bleeding (GIB). Its mortality is high, approaching 20%, despite
      recent advances in endoscopic therapy. We aimed to report our experience in the
      treatment of DL. METHODS: A retrospective case study of all patients with DL
      between January 1993 and January 2003 was done. Characteristics, treatment
      methods, success rates and 30-d mortality of the patients were analyzed. RESULTS:
      Thirty-six patients were noted to have DL in the study period. Thirty-three
      records were available for assessment in which 35 DL were identified. The median
      age of the patients was 67 years with male to female ratio of 5.6:1. Significant
      comorbidities existed in 69% of the patients. Eighty-nine percent of the DL was
      found at first endoscopy, three DL at laparotomy. Significant coexistent
      endoscopic findings existed in 23%. Hemostasis was achieved in 88% by using
      adrenaline injection, or in combination with heater probe application at first
      endoscopy. Four cases had re-bleeding, all were successfully treated
      endoscopically. The 30-d mortality rate was 23%. CONCLUSION: Successful
      endoscopic hemostasis could be achieved in 100% of cases of DL. The overall
      mortality may still remain high, mainly due to the comorbidities and age of these
      patients.

PMID- 15962379
TI  - Changes of gastric and intestinal blood flow, serum phospholipase A2 and
      interleukin-1beta in rats with acute necrotizing pancreatitis.
AB  - AIM: To explore the relationship between gastric and intestinal microcirculatory
      impairment and inflammatory mediators released in rats with acute necrotizing
      pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control
      group and ANP group. ANP model was induced by injection of 5% sodium taurocholate
      under the pancreatic membrane. Radioactive biomicrosphere technique was used to
      measure the gastric and intestinal tissue blood flow at 2 and 12 h after the
      induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and
      interleukin-1beta levels were determined. Pathologic changes in pancreas, gastric
      and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group
      (0.62+/-0.06 and 0.35+/-0.05) mL/(min.g) was significantly lower than that in
      control group (0.86+/-0.11 and 0.85+/-0.06) mL/(min.g) (P<0.01) at 2 and 12 h
      after induction of ANP. The intestinal blood flow in ANP group (0.80+/-0.07 and
      0.50+/-0.06) mL/(min.g) was significantly lower than that in control group
      (1.56+/-0.18 and 1.61+/-0.11) mL/(min.g) (P<0.01). Serum PLA2 activities (94.29+/
      9.96 and 103.71+/- 14.40) U/L and IL-1beta levels (0.78+/-0.13 and 0.83+/-0.20)
      microg/L in ANP group were higher than those in control group (65.27+/-10.52 and
      66.63+/-9.81) U/L, (0.32+/-0.06 and 0.33+/-0.07) betag/L (P<0.01). At 2 and 12 h
      after introduction of the model, typical pathologic changes were found in ANP.
      Compared with control group, the gastric and intestinal mucosal pathologic
      changes were aggravated significantly (P<0.01) at 12 h after induction of ANP.
      Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred.
      CONCLUSION: Decrease of gastric and intestinal blood flow and increase of
      inflammatory mediators occur simultaneously early in ANP, both of them are
      important pathogenic factors for gastric and intestinal mucosal injury in ANP.

PMID- 15962380
TI  - Transformation of hepatitis B serologic markers in babies born to hepatitis B
      surface antigen positive mothers.
AB  - AIM: To better understand the clinical significance of hepatitis B serologic
      markers in babies born to hepatitis B surface antigen (HBsAg) positive mothers,
      the incidence of maternal serologic markers of hepatitis B via placenta and its
      transformation in these babies were investigated. METHODS: Mothers with positive
      HBsAg were selected in the third trimester of pregnancy. Their babies received
      immunoprophylaxis with hepatitis B immunoglobulin and hepatitis B vaccine after
      birth, and were consecutively followed up for hepatitis B serologic markers and
      HBV DNA at birth, mo 1, 4, 7, 12, and 24. RESULTS: Forty-two babies entered the
      study, including 16 born to hepatitis B e antigen (HBeAg)-positive HBsAg carrier
      mothers and 26 to HBeAg-negative HBsAg carrier mothers. Apart from four babies
      born to HBeAg-positive carrier mothers and demonstrated persistent positive HBeAg
      eventually became HBV carriers, all other babies developed anti-HBs before 12 mo
      of age. Among the other 12 babies born to HBeAg-positive carrier mothers, HBeAg
      was detected in 7 at birth, in 4 at mo 1, and in none of them thereafter. No
      antibody response to the transplacental HBeAg was detected. Among the babies born
      to HBeAg-negative carrier mothers, anti-HBe was detected 100% at birth and mo 1,
      in 88.5% at mo 4, in 46.2% at mo 7, in 4.2% at mo 12 and none in mo 24. Among all
      the immunoprophylaxis-protected babies born to either HBeAg-positive or HBeAg
      negative carrier mothers, anti-HBc was detected in 100% at birth, mo 1 and mo 4,
      in 78.9% at mo 7, in 36.1% at mo 12 and in none at mo 24. CONCLUSION: HBeAg can
      pass through human placenta from mother to fetus and become undetectable before 4
      mo of age, but no antibodies response to the transplacental HBeAg can be detected
      till mo 24 in the immunoprophylaxis-protected babies. The sole existence of anti
      HBe before 1 year of age or anti-HBc before 2 years of age in babies born to
      HBsAg carrier mothers may simply represent the transplacental maternal
      antibodies, instead of indicators of HBV infection status.

PMID- 15962381
TI  - Nodal spread and micrometastasis within mesorectum.
AB  - AIM: To study the distribution of positive lymph nodes within mesorectum and to
      investigate the possible micrometastasis in negative lymph nodes. METHODS: Large
      slice technique combined with tissue microarray was used in the pathologic study
      of 31 specimens. RESULTS: A total of 992 lymph nodes were harvested and cancer
      metastasis was found in 148 lymph nodes. Some positive lymph nodes were located
      in the outer layer of mesorectum and more at the same site of mesorectum as the
      primary tumor. Circumferential margin lymph node metastasis was observed in nine
      cases. No significant difference in occurrence of micrometastasis was observed in
      different stage tumors. CONCLUSION: Positive lymph nodes are distributed in
      mesorectum and micrometastasis can be found in negative lymph nodes.

PMID- 15962382
TI  - Expression of CD44v6 gene in normal human peripheral blood.
AB  - AIM: To investigate if CD44v6 could be used as a molecular marker of cancer
      progression and metastasis through the detection of CD44v6 gene expression in
      normal human peripheral blood. METHODS: RNA was extracted from the peripheral
      blood mononuclear cells of 50 healthy donors, the expression of CD44v6 was
      investigated using reverse transcriptase-polymerase chain reaction (RT-PCR).
      RESULTS: CD44v6 mRNA was detected in 58% of healthy volunteers under the proper
      controls. CONCLUSION: Our results suggest that the measurement of CD44v6
      expression in peripheral blood by RT-PCR is not suitable for detection of
      circulating tumor cells.

PMID- 15962383
TI  - Differences in biological features of gastric dysplasia, indefinite dysplasia,
      reactive hyperplasia and discriminant analysis of these lesions.
AB  - AIM: To investigate the differences in biological features of gastric dysplasia
      (Dys), indefinite dysplasia (IDys) and reactive hyperplasia (RH) by studying the
      biomarker alterations in cell proliferation, cell differentiation, cell cycle
      control and the expression of house-keeping genes, and further to search for
      markers which could be used in guiding the pathological diagnosis of three
      lesions. METHODS: Expressions of MUC5AC, MUC6, adenomatous polyposis coli (APC),
      p53, Ki-67, proliferation cell nuclear antigen (PCNA) and EGFR were studied by
      immunohistochemistry with a standard Envision technique in formalin-fixed and
      paraffin-embedded specimens from 43 RH, 35 IDys, 35 Dys and 36 intestinal type
      gastric carcinomas (IGC). In addition, Bayes discriminant analysis was used to
      investigate the value of markers studied in differential diagnosis of RH, IDys,
      Dys and IGC. RESULTS: The MUC5AC and MUC6 antigen expressions in RH, IDys, Dys
      and IGC decreased gradually (MUC5AC: 86.04%, 77.14%, 28.57%, 6.67%; MUC6: 65.15%,
      54.29%, 20.00%, 25.00%, respectively). The expressions of the two markers had no
      significant difference between RH and IDys, but were all significantly higher
      than those of the other two lesions (MUC5AC: chi2=27.607, 38.027 and 17.33,
      26.092; MUC6: chi2=16.54, 12.665 and 9.282, 6.737, P<0.01). There was no
      significant difference between RH and IDys, Dys and IGC in MUC6 expression. The
      APC gene expression in the four lesions had a similar decreasing tendency (RH
      69.76%, IDys 68.57%, Dys 39.39%, IGC 22.86%), and it was significantly higher in
      the first two lesions than in the last two (chi2=7.011, 16.995 and 14.737,
      19.817, P<0.05). The p53 expression in RH, IDys, Dys and IGC was 6.98%, 20%,
      57.14% and 50%, respectively. There was no significant difference between RH and
      IDys or Dys and IGC, but the p53 expression in RH and IDys was significantly
      lower than that in Dys and IGC (chi2=7.011, 16.995 and 14.737, 19.817, P<0.01).
      The Ki-67 label index was significantly different among four lesions (RH: 0.298+/
      8.92%, IDys: 0.358+/-9.25%, Dys: 0.498+/-9.03%, IGC: 0.620+/-10.8%, P<0.001).
      Positive immunostaining of PCNA was though observed in all specimens, significant
      differences were detected among four lesions (F=95.318, P<0.01). In addition, we
      used Bayes discriminant analysis to investigate molecular pathological
      classification of the lesions, and obtained the best result with the combination
      of MUC5AC, Ki-67 and PCNA. The overall rate of correct classification was 67.4%
      (RH), 68.6% (IDys), 70.6% (Dys) and 84.8% (IGC), respectively. CONCLUSION: Dys
      has neoplastic biological characteristics, while RH and IDys display hyperplastic
      characteristics. MUC5AC and proliferation-related biomarkers (Ki-67, PCNA) are
      more specific in distinguishing Dys from RH and IDys.

PMID- 15962384
TI  - Co-expression of heat shock protein 70 and glucose-regulated protein 94 in human
      gastric carcinoma cell line BGC-823.
AB  - AIM: To investigate the co-expression and significance of heat shock protein 70
      (HSP70) and glucose-regulated protein 94 (grp94) in human gastric carcinoma cell
      line BGC-823. METHODS: The expression and localization of HSP70 and grp94 in
      human gastric carcinoma cell line BGC-823 were determined by immunocytochemistry
      and indirect immunofluorescence cytochemical staining. Flow cytometry was used to
      analyze the correlation between expression of HSP70, grp94 and cell cycle in BGC
      823 cell line. RESULTS: Gastric cancer cell line BGC-823 expressed high level of
      HSP70 and grp94. The positive rate of HSP70 and grp94 was 84.9+/-4.94% and 79.6+/
      5.16%, respectively. Both of them were stained in cell plasma. There was a
      significant difference compared with control group (1.9+/-0.94%, P<0.01). During
      the cell cycle, HSP70 and grp94 were continuously expressed in BGC-823.
      CONCLUSION: HSP70 and grp94 are highly expressed in human gastric carcinoma BGC
      823 cells through the whole cell cycle. There is no relationship between
      expression of HSP70, grp94 and cell cycle.

PMID- 15962385
TI  - Effects of L-arginine on serum nitric oxide, nitric oxide synthase and mucosal
      Na+-K+-ATPase and nitric oxide synthase activity in segmental small-bowel
      autotransplantation model.
AB  - AIM: To explore a simple method to create intestinal autotransplantation in rats
      and growing pigs and to investigate the effect of L-arginine supplementation on
      serum nitric oxide (NO), nitric oxide synthase (NOS) and intestinal mucosal NOS
      and Na+-K+-ATPase activity during cold ischemia-reperfusion (IR) in growing pigs.
      METHODS: In adult Wistar rat models of small bowel autotransplantation, a fine
      tube was inserted into mesenteric artery via the abdominal aorta. The superior
      mesenteric artery and vein were occluded. Isolated terminal ileum segment was
      irrigated with Ringer's solution at 4 degrees and preserved in the same solution
      at 0-4 degrees for 60 min. Then, the tube was removed and reperfusion was
      established. In growing pig models, a terminal ileum segment, 50 cm in length,
      was isolated and its mesenteric artery was irrigated via a needle with lactated
      Ringer's solution at 4 degrees. The method and period of cold preservation and
      reperfusion were described above. Ten white outbred pigs were randomly divided
      into control group and experimental group. L-arginine (150 mg/kg) was
      continuously infused for 15 min before reperfusion and for 30 min after
      reperfusion in the experimental group. One, 24, 48, and 72 h after reperfusion,
      peripheral vein blood was respectively collected for NO and NOS determination. At
      the same time point, intestinal mucosae were also obtained for NOS and Na+-K+
      ATPase activity measurement. RESULTS: In adult rat models, 16 of 20 rats
      sustained the procedure, three died of hemorrhage shock and one of deep
      anesthesia. In growing pig models, the viability of small bowel graft remained
      for 72 h after cold IR in eight of 10 pigs. In experimental group, serum NO level
      at 1 and 24 h after reperfusion increased significantly when compared with
      control group at the same time point (152.2+/-61.4 micromol/L vs 60.8+/-31.6
      micromol/L, t=2.802, P=0.02<0.05; 82.2+/-24.0 micromol/L vs 54.0+/-24.3
      micromol/L, t=2.490, P=0.04<0.05). Serum NO level increased significantly at 1 h
      post-reperfusion when compared with the same group before cold IR, 24 and 48 h
      post-reperfusion (152.2+/-61.4 micromol/L vs 75.6+/-16.2 micromol/L, t=2.820,
      P=0.02<0.05, 82.2+/-24.0 micromol/L, t=2.760, P=0.03<0.05, 74.2+/-21.9
      micromol/L, t=2.822, P=0.02<0.05). Serum NOS activity at each time point had no
      significant difference between two groups. In experimental group, intestinal
      mucosal NOS activity at 1 h post-reperfusion reduced significantly when compared
      with pre-cold IR (0.79+/-0.04 U/mg vs 0.46+/-0.12 U/mg, t=3.460, P=0.009<0.01).
      Mucosal NOS activity at 24, 48, and 72 h post-reperfusion also reduced
      significantly when compared with pre-cold IR (0.79+/-0.04 U/mg vs 0.57+/-0.14
      U/mg, t=2.380, P=0.04<0.05, 0.61+/-0.11 U/mg, t=2.309, P=0.04<0.05, 0.63+/-0.12
      U/mg, t=2.307, P=0.04<0.05). In control group, mucosal NOS activity at 1 and 24 h
      post-reperfusion was significantly lower than that in pre-cold IR (0.72+/-0.12
      U/mg vs 0.60+/-0.07 U/mg, t=2.320, P=0.04<0.05, 0.58+/-0.18 U/mg, t=2.310,
      P=0.04<0.05). When compared to the normal value, Na+-K+-ATPase activity increased
      significantly at 48 and 72 h post-reperfusion in experimental group (2.48+/-0.59
      micromol/mg vs 3.89+/-1.43 micromol/mg, t=3.202, P=0.04<0.05, 3.96+/-0.86
      micromol/mg, t=3.401, P=0.009<0.01) and control group (2.48+/-0.59 micromol/mg vs
      3.58+/-0.76 micromol/mg, t=2.489, P=0.04<0.05, 3.67+/-0.81 micromol/mg, t=2.542,
      P=0.03<0.05). CONCLUSION: This novel technique for intestinal autotransplantation
      provides a potentially consistent and practical model for experimental studies of
      graft cold preservation. L-arginine supplementation during cold IR may act as a
      useful adjunct to preserve the grafted intestine.

PMID- 15962386
TI  - Contrast-enhanced ultrasonographic imaging diagnosis on assessment of vascularity
      in liver metastatic lesions.
AB  - AIM: To investigate the vasculature of rabbit liver metastatic lesions by color
      Doppler imaging and power Doppler imaging (PDI) techniques. METHODS: Eight New
      Zealand rabbits with implanted VX2 liver tumors were used. All ultrasound
      examinations were performed with a HP 5500 color Doppler ultrasound scanner.
      Before and after the injection of contrast agent, the changes of gray scale and
      the periphery and intralesional blood flow of the liver metastatic lesion were
      carefully observed by B mode ultrasound, color Doppler flow imaging (CDFI) and
      PDI. RESULTS: Twelve lesions were found in the eight rabbits with implanted VX2
      liver tumors, whose diameter ranged from 1.6 to 4.8 cm. Echoes of these lesions
      were not characterized and has lack of specificity. After the injection of
      contrast agent, the numbers of dot or strip-like flow messages increased both at
      the periphery and inside of these lesions under the mode of CDFI and PDI, and
      were more pronounced under PDI. Morphology of intralesional vessels extended,
      even branched and some signals were clearly found encircling the lesion. And some
      vessels were found penetrating into the center of the lesion. CONCLUSION: PDI
      after injection of self-made echo contrast agent can show a pronounced
      sensitivity than that of B mode ultrasound and CDFI in diagnosis of vascularity
      of a metastatic lesion.

PMID- 15962387
TI  - Optimization of competitively differentiated polymerase chain reaction in
      detection of HBV basal core promoter mutation.
AB  - AIM: To improve competitively differentiated polymerase chain reaction (CD-PCR)
      in detection of HBV basal core promoter mutation. METHODS: Recombinant plasmid of
      double point mutation A1762T/G1764A in basal core promoter of HBV constructed by
      site-directed mutagenesis was used as mutant control. To reveal the deficiency
      mechanism of CD-PCR, relationship between the circle number of PCR and the
      increased speed of products of each competitive primer was comparatively studied.
      Diversified amount of dNTPs and mutual primer of the competitive primers were
      tried to optimize CD-PCR. Optimized CD-PCR was evaluated by detecting
      A1762T/G1764A mutation in recombinant plasmids and clinical sera from patients
      with HBV infection. RESULTS: The deficiency mechanism of CD-PCR was that the
      products of mismatched competitive primer grew fast when the amplification of
      matched primer entered into plateau stage, which led to decrease in or
      disappearance of the difference in the amount of their products. This phenomenon
      could be eliminated by reducing dNTPs to 10 micromol/L and mutual primer to about
      100 nmol/L. Optimized CD-PCR could detect both mutant and wild strain independent
      of the amount of templates and the number of PCR cycles. Its detection limit was
      10(3) copies/mL, about 50 copies/reaction. About 10% of mutant DNAs among wild
      type DNAs could be detected. A1762T/G1764A mutant was detected in 41.8% (51/122)
      of patients with HBV infection, but not detected in controls with negative HBsAg.
      CONCLUSION: Optimized CD-PCR can detect mutation independent of the amount of
      initial templates and the number of PCR cycles.

PMID- 15962388
TI  - Inhibition effect of Chinese herbal medicine on transcription of hepatitis C
      virus structural gene in vitro.
AB  - AIM: To investigate the inhibitory effect of Chinese herbal medicine on the
      transcription of hepatitis C virus (HCV) structural gene in Hela D cells.
      METHODS: Hela cell line was transfected with recombinant pBK-CMV-HCV containing
      HCV structural gene by Lipofectamine. RT-nested-PCR and Western blot assay were
      used to testify the HCV gene expression in Hela cells. The Hela cells expressing
      HCV structural protein were named Hela D cells. Prescriptions of Xiao chaihu
      Decoction (XCHD), Fufang Huangqi (FFHQ) and Bingganling (BGL) were respectively
      added to Hela D cells in various concentrations. Semi-quantitative RT-nested-PCR
      product analysis was performed according to the fluorescent density between HCV
      DNA band and GAPDH DNA band in gel electrophoresis after screened. RESULTS:
      Recombinant pBK-CMV-HCV could correctly express the HCV structural gene in Hela D
      cells. After co-culture of Hela D cells with three prescriptional different
      concentrations for 48 h respectively, the transcription of HCV gene decreased
      with increasing of the concentration of each prescription. The lightness ratio of
      HCV product bands to GAPDH product bands was 0.24, 0.10 and 0.12 in Hela D cells
      incubated with 0.1 g/mL of XCHD, FFHQ and BGL respectively and the lightness
      ratio HCV product bands to GAPDH product bands was 0.75, 0.67 and 0.61
      respectively in the control cells. CONCLUSION: The prescriptions of XCHD, FFHQ
      and BGL partly inhibit the transcription of HCV structural gene in Hela D cells.

PMID- 15962389
TI  - Single nucleotide polymorphism in DNA methyltransferase 3B promoter and its
      association with gastric cardiac adenocarcinoma in North China.
AB  - AIM: To investigate the association between single nucleotide polymorphism (SNP)
      in promoter of the DNA methyltransferase 3B (DNMT3B) gene and risk for
      development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA).
      METHODS: The hospital based case-control study included 212 GCA patients and 294
      control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and
      restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C
      genotype was not detected in both GCA patients and controls. In control subjects,
      the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that
      of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype
      distribution in the GCA patients was not significantly different from that in
      controls (P=0.34 and 0.33, respectively). When stratified by smoking status and
      family history of upper gastrointestinal cancer, significant difference in the
      genotype distribution was not observed between GCA patients and controls. The
      distribution of DNMT3B genotypes in GCA patients with or without lymphatic
      metastasis did not show significant difference (P=0.42). CONCLUSION: The
      distribution of DNMT3B SNP in North China is distinct from that in Caucasians.
      Although this SNP has been associated with susceptibility to lung, head, neck and
      breast cancer, it may not be used as a stratification marker to predict
      susceptibility and lymphatic metastasis of GCA, at least in the population of
      North China.

PMID- 15962390
TI  - Relationship between the downregulation of HLA class I antigen and
      clinicopathological significance in gastric cancer.
AB  - AIM: To discuss the expression of human leukocyte antigen (HLA) class I antigens
      in gastric cancer and correlate these with pathologic type and TNM stage.
      METHODS: The expression of HLA class I antigen was detected by
      immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer
      specimens with lymphatic metastasis and 22 controls of normal gastric mucosa
      using four monoclonal antibodies. RESULTS: The expression of HLA class I antigen
      (B/C locus) was significantly downregulated in gastric cancer and in lymphatic
      metastasis than that in normal gastric mucosa (chi2=7.712, P<0.05). The
      expression of other HLA class I antigens was also downregulated, but the change
      was slight. There was no relationship between the downregulation of HLA class I
      antigen and that of beta2m and LMP2. The expression of HLA class I (B/C locus)
      was statistically correlated with pathologic stage in gastric adenocarcinoma
      (chi2=4.164, P<0.05). CONCLUSION: The expression of HLA class I antigen (B/C
      locus) was obviously downregulated in gastric cancer and in lymphatic metastasis.
      This abnormal expression would provide the tumor cells with a way to avoid
      immunological recognition.

PMID- 15962391
TI  - Fas ligand expression in colon cancer: a possible mechanism of tumor immune
      privilege.
AB  - AIM: To detect the expression of Fas ligand (FasL) in colon cancer tissues and
      cell lines and analyze the function of FasL-expressing colon cancer cells in
      inducing Fas-sensitive T lymphocyte apoptosis. METHODS: Ninety surgically
      resected colon cancer tissues and 15 hepatic metastasis specimens were
      investigated by immunohistochemical method with normal colon mucosa and colon
      adenoma as control. The relationship between FasL expression and pathologic
      features was also analyzed. FasL expression of 4 colon cancer cell lines, SW620,
      Lovo, LS-174T and SW1116, were detected by Western blotting assay. The function
      of FasL expressed on colon cancer cells was determined by coculture assay with
      Jurkat T lymphocytes, the apoptotic rate of which was detected by flow cytometry
      assay. RESULTS: Fifty-six (62.22%) cases of all the 90 colon cancer tissues and
      all (100%) the liver metastasis specimens expressed FasL, significantly higher
      than normal colon mucosa and colonic adenoma. Higher expression of FasL was found
      in more advanced stage of colon cancer and in cancer tissues with lymphatic or
      hepatic metastasis. All the colon cancer cell lines were found to express FasL.
      After coculture with the SW1116 cells for 24 h with an effector: target ratio
      10:1, the rate of apoptosis of Jurkat cells rose from 1.9% to 21.0%. CONCLUSION:
      The expression of FasL is upregulated in colon cancer and the functionally
      expressed FasL can induce apoptosis of Fas-expressing T lymphocytes.

PMID- 15962392
TI  - Application of endoscopic sphincterotomy in acute pancreatitis with fluid
      collection: a prospective study.
AB  - AIM: To elucidate the role of endoscopic sphincterotomy (EST) in the treatment of
      acute pancreatitis. METHODS: Ninety patients with acute pancreatitis were
      randomly divided into two groups: EST group and control group. All the patients
      underwent pancreatitis routine therapy, additionally the EST group was treated
      with EST and endoscopic naso-bile drainage (ENBD). The time of disappearance of
      abdominal symptoms and signs, normalization of amylase, hospitalization and
      absorption of acute fluid was recorded for all patients. RESULTS: The time of
      disappearance of abdominal pain, normalization of blood and urine amylase and
      hospitalization was significantly shorter in EST group than in control group. The
      ratios of disappearance of fluid in mild acute pancreatitis patients was
      significantly higher in EST group (51.52%, 84.85%, 90.91%, 93.94%) than in the
      control group (0%, 30.30%, 69.70%, 72.73%, P<0.01 or P<0.05). When the ratios of
      reduction of fluid in severe acute pancreatitis patients of the EST group were
      compared (8.33%, 58.33%, 83.33%, 91.67%) with those in the control group (0%,
      8.33%, 25% and 41.67%), there were significant differences. CONCLUSION: The
      effect of EST+ENBD on acute pancreatitis with fluid is rather good.

PMID- 15962393
TI  - Detection of lymph nodes micrometastases in Dukes' A and B colorectal cancer
      using anti-cytokeratin antibodies AE1/AE3.
AB  - AIM: To detect lymph nodes micrometastases and analyze its correlation with
      clinicopathological parameters in Dukes' A and B colorectal cancer patients.
      METHODS: One hundred and fourteen patients with colorectal cancer (Dukes' A 16;
      Dukes' B 98) undergoing curative operation without histological lymph nodes
      metastases were studied between 2001 and 2003. A total of 2,481 lymph nodes were
      analyzed using monoclonal cytokeratin antibody AE1/AE3 (DAKO, Carpinteria, CA)
      for immunohistochemistry. RESULTS: In total, 33 (29%) patients were positive for
      cancer cell by immunohistochemistry. In 31 (94%) patients of them positive nodes
      showed single tumor cell or small groups of tumor cells; and tumor deposits
      measuring 0.2 and 0.37 mm in diameter in another 2 (6%) patients. Micrometastases
      were mainly located in the subcapsular sinus or paracortical sinus. There was no
      correlation between the positive lymph nodes and gender, age, tumor site, tumor
      size, histological type, histological grade, invasion depth, Dukes' staging and
      microsatellite instability (P>0.05). CONCLUSION: Our findings suggest that
      immunohistochemical technique using monoclonal cytokeratin antibody AE1/AE3 may
      be a sensitive and reliable method for detecting lymph nodes micrometastases in
      Dukes' A and B colorectal cancer. The clinical significance of lymph nodes
      micrometastases is still not confirmed.

PMID- 15962395
TI  - Acute cholestasis related to desloratidine.

PMID- 15962394
TI  - The value and limitation of transcatheter arterial chemoembolization in
      preventing recurrence of resected hepatocellular carcinoma.
AB  - AIM: To evaluate the value and limitation of postoperative transcatheter arterial
      chemoembolization (TACE) in preventing recurrence of hepatocellular carcinoma
      (HCC). METHODS: In the first group, 987 postoperative patients with HCC, who did
      not have any evidence of recurrence in the first preventative TACE but were found
      to have recurrence at different times during the follow-up survey, were analyzed.
      In the second group, 643 postoperative patients with HCC had no TACE for compared
      study. To study the relationship between the recurrence time and the number of
      TACE treatments was analyzed. RESULTS: The 6-, 12-, and 18-mo recurrence rates in
      the first and second groups were 22.2% (210 cases) vs 61.6% (396 cases), 78.0%
      (770 cases) vs 74.7% (480 cases) and 88.6% (874 cases) vs 80.1% (515 cases).
      There were significant differences between the recurrence rates of the two groups
      at 6 mo (P<0.0001). CONCLUSION: The principal role of TACE after HCC operation is
      to suppress, detect early and treat micro-metastasis. It has a good effect of
      preventing recurrence of HCC in 6 mo, but such an effect is less satisfactory in
      a longer period. When it is uncertain whether HCC is single-central or multi
      central and if there is cancer residue or metastasis after operation, TACE is
      valuable to prevent recurrence.

PMID- 15962396
TI  - Erythropoietin in liver cirrhosis: two questions without answers.

PMID- 15962397
TI  - Bibliography. Current world literature. General otolaryngology.

PMID- 15962398
TI  - Bibliography. Current world literature. Allergy.

PMID- 15962399
TI  - Mirrored EMG activity during unimanual rhythmic movements.
AB  - We studied instances of mirror movements--in the form of coherent EMG activity of
      the muscles in the arm not intended to move--during the performance of a
      unimanual rhythmic task in healthy adults. Epochs of involuntary muscle activity
      were detected and analyzed using time-resolved spectral methods. The observed
      frequency and phase locking between EMG patterns derived from homologous extensor
      muscles indicated the presence of neural cross-talk, which is relevant to the
      study of interlimb coordination.

PMID- 15962400
TI  - Is vitamin A implicated in the pathophysiology of increased intracranial
      pressure?

PMID- 15962401
TI  - Laparoscopic pancreatic resection: results of a multicenter European study of 127
      patients.
AB  - BACKGROUND: The reported experience with laparoscopic pancreatic resections (LPR)
      remains limited to case reports or small series of patients. METHODS: A
      retrospective multicenter study was conducted in 25 European surgical centers
      concerning their experience with LPR. Detailed questionnaires were used, focusing
      on patients, tumors, operative data, and late outcome. RESULTS: During the study
      period, 127 patients with presumed pancreatic neoplasms were enrolled in this
      series. Final diagnoses included benign pancreatic diseases in 111 patients (87%;
      insulinoma: 22, neuroendocrine neoplasm: 20, mucinous cystadenoma: 26, serous
      cystadenoma: 21, chronic pancreatitis: 11, others: 11), and 16 patients (13%) had
      malignant pancreatic diseases (insulinoma: 3, neuroendocrine neoplasm: 5, ductal
      adenocarcinoma: 4, cystadenocarcinoma: 2, renal metastases: 2). Five patients
      with presumed benign pancreatic disease had malignancy at final pathology. The
      median tumor size was 30 mm (range, 5-120 mm); 89% of tumors were located in the
      left pancreas. Laparoscopically successful procedures included 21 enucleations,
      24 distal splenopancreatectomies, 58 distal pancreatectomies with splenic
      preservation, and 3 pancreatoduodenal resections. The overall conversion rate was
      14%. There were no postoperative deaths. The rate of overall postoperative
      pancreatic-related complications was 31%, including a 17% rate of clinical
      pancreatic fistula. The surgical reoperation rate was 6.3%. In laparoscopically
      successful operations, the median postoperative hospital stay was 7 days (range,
      3-67 days), decreased compared with patients requiring conversion to open
      pancreatectomy. During a median follow-up of 15 months (range, 3-47 months), 23%
      of the patients with pancreatic malignancies had tumor recurrence. Late outcome
      was satisfactory in all patients with benign diseases. CONCLUSIONS: LPR is
      feasible and safe in selected patients with presumed benign and distal pancreatic
      tumors. The management of the pancreatic stump remains a challenge. The role of
      LPR for pancreatic malignancies remains controversial.

PMID- 15962402
TI  - The Role of IGF Parameters in the Management of Growth Disorders and Acromegaly -
      Diagnosis, Efficacy and Safety. Proceedings of the 7th KIGS/KIMS Expert Meeting
      on Growth Hormone and Growth Disorders. Paris, France, January 16-17, 2004.

PMID- 15962403
TI  - Transmission of rabies from an organ donor.

PMID- 15962404
TI  - Transmission of rabies from an organ donor.

PMID- 15962405
TI  - What ails the FDA?

PMID- 15962406
TI  - What ails the FDA?

PMID- 15962407
TI  - What ails the FDA?

PMID- 15962408
TI  - Obesity and longevity.

PMID- 15962410
TI  - Obesity and longevity.

PMID- 15962409
TI  - Obesity and longevity.

PMID- 15962411
TI  - Obesity and longevity.

PMID- 15962412
TI  - Brain-healthy strategies.

PMID- 15962413
TI  - The many benefits of boosting HDL.

PMID- 15962414
TI  - Gene profiling coming of age in cancer therapy.

PMID- 15962415
TI  - The A's and B's of sunscreen.

PMID- 15962416
TI  - My everyday body temperature is 97.4 degrees F, below the normal 98.6 degrees F
      (37 degrees C). So am I running a fever if my temperature is 99 degrees F?

PMID- 15962417
TI  - Kitchen equipment. A user's guide.

PMID- 15962418
TI  - Strike the spike. Controlling after-meal blood glucose highs.

PMID- 15962419
TI  - Living alone and living well with diabetes.

PMID- 15962420
TI  - Convenience cooking step by step.

PMID- 15962421
TI  - Diabetes quiz. How much do you know about protein?

PMID- 15962422
TI  - CIT. A therapy for stroke recovery.

PMID- 15962423
TI  - Women & diabetes. Urinary incontinence.

PMID- 15962424
TI  - Supermarket smarts. Frozen dinners and entrees.

PMID- 15962425
TI  - Foot care. Drugstore do's and don't's.

PMID- 15962426
TI  - Puerto Rico cuisine. Spicy and flavorful.

PMID- 15962427
TI  - Helping young children succeed with diabetes care.

PMID- 15962428
TI  - Gluten-free food companies.

PMID- 15962429
TI  - Big question for 2005: what happened to CDC's HIV prevention plan? Experts say
      U.S. is long way from meeting goals.
AB  - Although the CDC has reached the year when its strategic plan for HIV prevention
      was supposed to be realized, little has changed since the plan was published in
      January 2001, experts say. For example, the HIV new infection rate has not
      changed at all, according to official estimates, and about the same proportion of
      HIV-infected individuals do not know their HIV status. Some experts claim the
      fault has been a lack of federal funding to back up the ambitious goals.

PMID- 15962430
TI  - CDC plans to persevere with prevention efforts.
AB  - In this Q & A, AIDS Alert interviews Ronald Valdiserri, MD, MPH, deputy director
      of the National Center for HIV, STD, and TB Prevention at the CDC. Valdiserri
      discusses what has been achieved by the HIV Prevention Strategic Plan Through
      2005, and what more needs to be accomplished.

PMID- 15962431
TI  - CDC issues guidelines on treating OIs among adults. ART is cornerstone of
      treatment plan.
AB  - The CDC has confirmed that in the age of antiretroviral therapy clinicians may
      choose to treat some opportunistic infections (OIs) less aggressively. The CDC's
      recent guidelines emphasize the importance of antiretroviral therapy in reducing
      the incidence of OIs, particularly in individuals who have a CD4 t-cell count of
      less than 200 cells. But they also confirm that some OI treatment might pose more
      risks than benefits.

PMID- 15962432
TI  - Reaching rural African American women difficult. Researcher discusses chief
      issues.
AB  - Poverty and inequality are among the major challenges faced by the rural African
      American women at risk for HIV infection, and they increase this population's
      potential for becoming infected, an expert says.

PMID- 15962433
TI  - New tool measures potential for adherence. Tool is part of multidisciplinary
      approach.
AB  - A team of HIV clinicians and medical professionals at Weill Cornell Medical
      Center at New York Presbyterian Hospital have developed an assessment tool that
      is used to identify a new HIV patient's potential for adherence. The tool,
      consisting of 20 questions, was designed to assess the psychosocial factors that
      could influence a patient's adherence to antiretroviral therapy, according to a
      senior social worker in the Center for Special Studies at Weill Cornell.

PMID- 15962434
TI  - African women push for HIV disclosure law.

PMID- 15962435
TI  - Prevention. Battle brews to prevent HIV/AIDS through condom distribution.

PMID- 15962436
TI  - Settlement. Lambda Legal reaches agreement in HIV discrimination suit.

PMID- 15962437
TI  - Prevention. Catholics advise condoms to prevent AIDS in Honduras.

PMID- 15962438
TI  - Medicare. Advocates: Congressional cuts would hurt HIV health care.

PMID- 15962439
TI  - Prevention. ACLU: abstinence program promotes Christianity with taxes.

PMID- 15962441
TI  - Disclosure. Victim's HIV status to be redacted from court documents.

PMID- 15962440
TI  - Prisons. Inmate must allege HIV exposure to demand test.

PMID- 15962443
TI  - Comprehensive update on antiretroviral therapy in HIV-infected children.

PMID- 15962442
TI  - Policy. U.S. backs off stipulation on AIDS funds under criticism.

PMID- 15962444
TI  - Incarceration creates special issues for HIV clinicians.

PMID- 15962445
TI  - Nursing. How can clinicians help motivate their clients to change?

PMID- 15962446
TI  - Dental services in the RWCA: implications for reauthorization.

PMID- 15962447
TI  - Multidrug-resistant HIV.

PMID- 15962448
TI  - Methicillin-resistant Staphylococcus aureus infection in a man with HIV disease.

PMID- 15962449
TI  - Recent developments in HIV treatment, Part 2.

PMID- 15962450
TI  - FDA approves once-daily Kaletra.

PMID- 15962451
TI  - Memory loss in persons with HIV/AIDS: assessment and strategies for coping.
AB  - Although the incidence of HIV-related dementia has decreased significantly in the
      era of contemporary HAART, the prevalence of memory and cognitive symptoms
      remains steady in persons with HIV/AIDS. Recognition of which memory symptoms may
      be specifically related to HIV infection is becoming more and more challenging
      because of the increased survival and aging of those living with HIV disease.
      Therefore, numerous age-related causes of memory impairment may need to be ruled
      out. Depression can often result in subjective memory symptoms but rarely causes
      objective cognitive impairment. Because of the widespread use of thiamine food
      supplementation, alcohol is now a less common cause of severe memory impairment.
      HAART remains the treatment of choice for HIV-related dementia.

PMID- 15962452
TI  - Editorial comment: treatment of HIV-associated cognitive impairment--beyond
      HAART.

PMID- 15962453
TI  - Effect of recombinant human growth hormone on exercise capacity in patients with
      HIV-associated wasting on HAART.
AB  - Over 700 patients with HIV-associated wasting while receiving HAART were randomly
      assigned to double-blind treatment for 12 weeks with recombinant human growth
      hormone (rhGH) daily or on alternate days, or to placebo. Maximum exercise
      intensity increased by a median of 2.35kJ in the alternate-days group and 2.60 kJ
      in the daily group but decreased by 0.25kJ in the placebo group. The median
      difference between the daily and placebo groups was 2.85 kJ (P < .0001). These
      improvements suggest that rhGH treatment may enable patients with wasting to
      perform activities of daily living that would be exhausting without rhGH
      treatment.

PMID- 15962454
TI  - Editorial comment: use of recombinant human growth hormone for wasting--questions
      for clinical practice.

PMID- 15962455
TI  - African lentiviruses related to HIV.

PMID- 15962456
TI  - Clinical Gallery. Manifestations of neonatal herpes and herpetic cervicitis.

PMID- 15962457
TI  - The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among
      disorders of mood and affect. Proceedings of a roundtable meeting.
AB  - This monograph summarizes the proceedings of a roundtable meeting convened to
      discuss pseudobulbar affect (PBA). Two didactic lectures were presented followed
      by a moderated discussion among 11 participants. Post-meeting manuscript
      development synthesized didactic- and discussion-based content ad incorporated
      additional material from the neuroscience literature. A conceptual framework with
      which to distinguish between disorders of mood and affect is presented first, and
      disorders of affect regulation are then reviewed briefly. A detailed description
      of the most common of these disorders, PBA, is the focus of the remainder of the
      monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA
      are reviewed, and current and emerging methods of evaluation and treatment of
      persons with PBA are discussed. The material presented in this monograph will
      help clinicians better recognize, diagnose, and treat PBA, and will form a
      foundation for understanding and interpreting future studies of this condition.

PMID- 15962458
TI  - What will the new World Bank head do for global health?

PMID- 15962459
TI  - This new mosquito repellent is a match for the standby.

PMID- 15962460
TI  - Assisted living. How much assistance can you really count on?

PMID- 15962461
TI  - Probiotics. Are enough in your diet?

PMID- 15962462
TI  - Vitamin E pills. Now it's thumbs down.

PMID- 15962463
TI  - Annotated bibliography of NINR findings on women's health in pregnancy and
      childbirth: 2005 update. National Institute of Nursing Research, National
      Institutes of Health, U.S. Department of Health and Human Services.

PMID- 15962464
TI  - NICE guideline on antenatal care: routine care for the healthy pregnant woman-
      recommendations on the use of complementary therapies do not promote clinical
      excellence.

PMID- 15962465
TI  - The need for effective disease control in international aquaculture.
AB  - Globally, aquaculture is steadily expanding both in terms of total production and
      the range of species farmed. At an overall annual growth rate of about 10%, it is
      by far the fastest growing sector of food animal production in the world and is
      providing an increasing proportion of the total production of fish and shellfish
      for human consumption. However, diseases continue to cause significant economic
      losses in international aquaculture production and to have a detrimental effect
      on valuable export trade for some countries. Financial losses have been drastic
      in some cases and the national economies of some developing countries have been
      adversely affected. Even just at the local level, disease can have a serious
      impact on the livelihoods and food security of many individual small farmers and
      their families, particularly in poorer countries. Despite all the problems
      caused, diseases continue to be spread internationally even where import health
      safeguards are in place. Recent examples of such spread are presented and some
      reasons for the appearance of a disease in a country for the first time are
      given. It is an unfortunate fact that despite many years of damaging economic and
      social impact of disease in different sectors of aquaculture, and large sums
      being spent on research around the world, there are relatively few effective and
      officially approved products available to control or prevent them. Despite the
      potential market, there are as yet no commercial vaccines available to prevent
      the damaging effects of many of the most serious diseases. Without such vaccines,
      it is likely that the serious impact of diseases in international aquaculture
      will continue for many years to come.

PMID- 15962466
TI  - Eradication versus vaccination strategies to control infectious diseases--some
      lessons to be learned from terrestrial animals.
AB  - In the pre-vaccine era, highly contagious and dangerous animal virus diseases had
      enormous socio-economic impacts on societies, and the only way of control was a
      vigorous stamping-out strategy. Diseases that were difficult to diagnose on
      clinical grounds could not be contained and often became endemic. Considerable
      progress in the control of viral infections of farm animals was made when their
      viral aetiology became known and means for the propagation of the infectious
      agents, first in animals and later in cell culture, were developed. This led to
      the development of several generations of vaccines that were applied with
      increasing success in the control of infectious diseases. Inactivated as well as
      live attenuated vaccines were successfully used, as shown in the control of
      classical swine fever and foot-and-mouth disease. Recently both inactivated and
      live "marker" vaccines have been added or will be added to the repertoire of
      tools for the control and eradication of infectious diseases. Attempts to
      eradicate endemic Aujeszky's disease from pig populations are greatly facilitated
      by the systematic use of deletion marker vaccines. Currently the use of marker
      vaccines for emergency use to contain outbreaks of classical swine fever and foot
      and-mouth disease is under discussion between stakeholders and legislators.

PMID- 15962467
TI  - Adaptive immunity in teleosts: cellular immunity.
AB  - Specific cell-mediated immunity in fish is to date a relatively poorly studied
      area in fish immunology. Despite breakthroughs in the cloning of the fish TcR and
      major histocompatibility (MHC) molecules, and more recently the CD3 and CD8
      marker molecules, assays to measure specific T-cell responses are still in their
      infancy. The classical division of T cells into cytotoxic (Tc) and helper (Th)
      subpopulations is probably relevant to fish, based on the presence of these
      functional activities and MHC class I and II molecules, but as yet even this is
      not definitively proved. This review will consider which specific cell-mediated
      responses can be measured within fish and what their relevance is to fish
      vaccination programmes.

PMID- 15962468
TI  - Immune functions in crustaceans: lessons from flies.
AB  - In recent years insects, notably Drosophila, have emerged as a popular model for
      studying immune responses to bacterial and fungal pathogens. Due to the
      availability of the complete genome sequence, genome-wide scans of immune
      responses have been performed using microarray analyses. These analyses have
      revealed the presence of two major pathways: Toll and Imd. Each pathway consists
      of four steps: (i) recognition through pattern recognition receptors; (ii)
      modulation by serine proteases; (iii) signal transduction leading to
      translocation of transcription factors and (iv) humoral and cellular responses.
      We have compared the information from insects with those currently available in
      crustaceans, and have identified commonalities and differences. Remarkably, in
      both insects and crustaceans, little is known about their anti-viral responses.
      Future research will have to focus on these anti-viral immune responses
      ultimately to control viral diseases, which are at present a major threat to
      culturing penaeid shrimp.

PMID- 15962469
TI  - Identification of expressed genes in carp (Cyprinus carpio) head kidney cells
      after in vitro treatment with immunostimulants.
AB  - We analysed a total of 530 expressed genes from the head kidney cells of common
      carp (Cyprinus carpio) treated by immunostimulants. Sequences of the cDNA clones
      were compared with sequences in the GenBank database. Immune-related genes
      identified after in vitro stimulation of carp head kidney cells were: BPI/LBP, C
      type lectins, fucolectins, CC-chemokine, CXC-chemokine, CD18, cyclophilin,
      FcgammaR, G-CSFR, HSP 70, Ig heavy and light chains, NITR, integrin beta2-alpha,
      Mx, interleukin-1beta, beta thymosin, lysozyme G & C, MHC class II associated
      invariant chain 1 and 2, granulin, CAAT binding protein and tumour necrosis
      factor-alpha induced protein. The expression of these immune-related genes may be
      important for estimating the efficacy of immunostimulants.

PMID- 15962470
TI  - Bacterial vaccines for fish--an update of the current situation worldwide.
AB  - During the last few years, the use of vaccines for disease prevention in
      aquaculture has expanded both with regard to the number of fish species and
      number of microbial diseases. According to the responses to a questionnaire
      received from 41 countries, vaccination is used in the commercial aquaculture of
      species like Atlantic salmon (Salmo salar), rainbow trout (Oncorhynchus mykiss),
      sea bass (Dicentrarchus labrax), sea bream (Sparus aurata), barramundi (Lates
      calcarifer), tilapia (Tilapia spp), turbot (Scophthalmus maximus L.), yellowtail
      (Seriola quinqueradiata), purplish and gold-striped amberjack (Seriola dumereli),
      striped jack (Pseudocaranx dentex) and channel catfish (Ictalurus punctatus). The
      range of bacterial infections for which vaccines are commercially available now
      comprises classical vibriosis (Listonella anguillarum, Vibrio ordalii),
      furunculosis (Aeromonas salmonicida subsp. salmonicida), cold-water vibriosis
      (Vibrio salmonicida), yersiniosis (Yersinia ruckeri), pasteurellosis
      (Photobacterium damselae supsp. piscicida), edwardsiellosis (Edwardsiella
      ictaluri), winter ulcer (Moritella viscosa), and streptococcosis/lactococcosis
      (Streptococcus iniae, Lactococcus garviae). Furthermore, experimental vaccines
      are used against diseases such as infection with Vibrio harveyi and
      Photobacterium damsela subsp. damsela in barramundi, piscirickettsiosis and
      bacterial kidney disease in salmonids, as well as infection with Flexibacter
      maritimus (now: Tenacibaculum maritimum) in turbot. There was good agreement
      between the information received from different sources in the same country. Most
      vaccines are licensed products, but some non-licensed vaccines are also used in
      commercial fish farms. Most bacterial vaccines are inactivated products and
      recombinant vaccine technology has so far been used to a very limited extent.
      Salmonid fish are usually immunised with multivalent vaccines by intraperitoneal
      injection. In marine fish species vaccination is generally performed by
      immersion, but use of injection vaccination is increasing, particularly in the
      Mediterranean region. Only limited use of orally administered fish vaccines is
      reported. In general, the effect of vaccination against bacterial infections is
      good. The best protection is obtained with injectable, adjuvanted vaccines.
      However, injection-site adverse reactions often occur when such products are
      used.

PMID- 15962471
TI  - Update on bacterial vaccines: Photobacterium damselae subsp. piscicida.
AB  - Photobacterium damselae subsp. piscicida is the causative agent of pasteurellosis
      in wild and farmed marine fish worldwide. Although serologically homogeneous,
      recent molecular advances have led to the discovery of distinct genetic clades,
      depending on geographical origin. Further details of the strategies for host
      colonisation have arisen including information on the role of capsule,
      susceptibility to oxidative stress, confirmation of intracellular survival in
      host epithelial cells, and induced apoptosis of host macrophages. This improved
      understanding has given rise to new ideas and advances in vaccine technologies,
      which are reviewed in this paper.

PMID- 15962472
TI  - Vaccination strategies to prevent emerging diseases for Spanish aquaculture.
AB  - In recent years, three serious diseases have emerged in Spanish aquaculture.
      These are lactococcosis caused by Lactococcus garvieae, which is of economical
      importance in rainbow trout (Oncorhynchus mykiss); pseudomonadiasis caused by
      Pseudomonas anguilliseptica which affects gilthead seabream (Sparus aurata) and
      turbot (Scophthalmus maximus); and flexibacteriosis caused by Tenacibaculum
      maritimum which became a devastating problem in the emerging culture of sole
      (Solea spp). To obtain useful information for the design and development of new
      vaccines, antigenic characterisation of representative strains was performed. In
      this work we present the strategies adopted for the vaccine formulation (strains
      included, use of adjuvants) and administration (route, necessity of booster,
      etc.). The results from laboratory and/or field vaccination trials performed
      showed that for lactococcosis, protection lasting for five months was obtained
      with an oil-adjuvanted bacterin formulation. Unadjuvanted bacterin gave only a
      short duration of protection, which could, however, be prolonged by an antigen
      boost administered via the feed. A bacterin against Pseudomonas anguilliseptica
      gave protection for 12 weeks when tested in an experimental challenge trial in
      turbot. Besides the flexibacteriosis vaccine developed by our group for turbot,
      and due to the antigenic host-associated variability within T. maritimum, a new
      bacterin was developed against this bacterium to be used specifically in sole.
      This new bacterin, administered to sole by intraperitoneal injection, yielded RPS
      values of 94 % six weeks after immunization. In conclusion, these results suggest
      that vaccination constitutes a cost-effective method of controlling diseases that
      have emerged in the most important fish species being cultured in Spain.

PMID- 15962473
TI  - Update on viral vaccines for fish.
AB  - A substantial amount of research has been done on fish viruses affecting species
      in aquaculture. This review will focus on the salmonid industry, as this is the
      most industrialised part of fish farming where vaccines are extensively used. In
      spite of the amount of research performed, both in commercial companies and in
      academic organisations, few viral vaccines are licensed. As of today, all fish
      virus vaccines for sale are based upon inactivated virus or recombinant proteins.
      No live attenuated or DNA vaccines are currently licensed, but one DNA vaccine
      against IHN is being tested in controlled field trials in Canada. Vaccines
      against infectious pancreatic necrosis (IPN) have been sold for many years in
      Norway and are now also available in Chile. Most of the research on these
      vaccines has been performed by pharmaceutical companies, and not much information
      is available as scientific publications. It has also been difficult to establish
      reproducible IPN challenge models suitable for vaccine testing and this probably
      explains the lack of scientific publications. Quite the reverse is the case for
      the fish rhabdoviruses viral hemorrhagic septicaemia virus (VHSV) and infectious
      haematopoietic necrosis virus (IHNV). The challenge models are reproducible, and
      both inactivated virus and DNA vaccines offer excellent protection. Recombinant
      subunit vaccines have so far shown unsatisfactory effect. Little information has
      been published regarding vaccine development against pancreas disease (PD) and
      infectious salmon anaemia (ISA). PD and ISA vaccines have been tested at the
      laboratory scale with good results, and two commercial ISA vaccines are currently
      available in Canada. Regarding nodaviruses, a few publications have shown effect
      of recombinant subunit formulations. However, nodaviruses cause disease early in
      the lifecycle of marine fish, and injection of these formulations into fish of a
      few grams is so far difficult on a commercial scale.

PMID- 15962474
TI  - The vaccine formulation and its role in inflammatory processes in fish--effects
      and adverse effects.
AB  - Adjuvants are helper substances that assist in the development of vaccine
      efficacy by enhancing the magnitude, extending the duration and/or directing the
      nature of the immune response. Most fish vaccines for injection are formulated
      with oil adjuvants and provide a strong and long-lasting immunity. Inherent
      problems of such formulations are the injection-site reactions, the challenge
      being to balance adjuvanticity against reactogenicity to produce a sufficient
      level of protection with as few side-effects as possible. Current findings on
      cellular inflammatory responses to oil adjuvanted vaccines in fish and on
      prediction factors for the effect versus side-effect balance are being discussed.
      The focus of future vaccine formulation studies will probably comprise the effect
      of formulation parameters on antigen retention, and the effect of antigen purity
      and concentration on recipient fish responses at the cellular and cytokine level.

PMID- 15962475
TI  - Vaccine adjuvant technology: from theoretical mechanisms to practical approaches.
AB  - Poorly immunogenic antigens depend on vaccine adjuvants to evoke an immune
      response. In addition, adjuvants largely determine the magnitude, quality, time
      of onset and the duration of immune responses to co-administered antigens. As
      late as 1989, Janeway aptly called adjuvants: "the immunologist's dirty little
      secret". This statement reflected the ignorance on the mechanisms of action of
      most known adjuvants. Yet, rational vaccine design involves a logical choice of
      adjuvant based on a knowledge of their mode of action and their effects on
      product efficacy and safety. However, even today the key processes critical for
      immune induction in general and those evoked by vaccine adjuvants in particular
      are being disputed among immunologists. This paper presents the four most
      important concepts likely to explain some of the mechanisms of vaccine adjuvants.
      They include: (i) the geographical concept of immune reactivity; (ii) the depot
      concept; (iii) the hypothesis of pathogen-structure recognition, and (iv) the
      damage/endogenous danger theory. These paradigms are based on observations
      gathered in mammalian species, largely in murine models. In aquatic animals the
      processes underlying immune induction will at least partly overlap those in
      mammals. However, due to inherent species differences, certain pathways may be
      different. Rational vaccine design, a difficult goal in mammals, is further
      hampered in aquatic animals by the lack of immunological tools in these species.
      Extensive trial and error-based approaches have yielded adjuvant candidates for
      various fish species, with acceptable safety and proven efficacy, some of which
      are presented.

PMID- 15962476
TI  - Immunisation of fish by bath immersion using ultrasound.
AB  - Ultrasonic irradiations (USI) as a means to open routes in the skin, thus
      facilitating the transdermal delivery of vaccines that will improve the
      effectiveness of vaccination by immersion, are reviewed in this paper. Based on
      our recent results in goldfish and carp it could be summarized that: (i) USI
      significantly improved the antigen uptake and enhanced antibody response; (ii)
      the requirements for high antigen concentrations, which are needed for simple
      bath immersion, could be considerably reduced in presonicated fish; (iii) after
      bath immersion, the antigen was slowly released from the skin to the blood in
      which its presence could still be detected 24 hours later. This retardation of
      the antigen in the skin was suggested to be due to a possible interaction with
      cells of the local immune system, in which it is processed and recognized. It is
      concluded that the recent advances in biotechnology of immunization with
      recombinant DNA and the use of DNA vaccines, together with the improvement of
      their administration using USI, provide interesting prospects for the further
      application of vaccines against viral and even parasitic diseases of fish.

PMID- 15962477
TI  - Development of a cost-effective oral vaccination method against viral disease in
      fish.
AB  - Different vaccination methods have been applied to protect fish against the
      detrimental effects of various pathogens. Several studies have shown the
      potentials of oral vaccination. In theory oral vaccination is an effortless and
      stress-free method which can be applied at almost any age. In general, however,
      the vaccine has to be protected to avoid digestion, which results in high costs
      for application in aquaculture. In this paper we introduce a cost-effective oral
      vaccination strategy for viral diseases of fish. The vaccines discussed here
      include fusion proteins consisting of a gut adhesion molecule and a viral peptide
      expressed in plants. The adhesion molecule mediates binding to and uptake from
      the gut, whereas the viral peptide functions as vaccine antigen mediating the
      induction of a humoral immune response. The first pilot studies using a fusion of
      the gut adhesion molecule and well-characterised heterologous linear B- and T
      cell viral epitopes, produced in potato tubers, showed a promising binding and
      subsequent uptake in the end gut of carp. The results further indicated that a
      specific humoral immune response was evoked.

PMID- 15962478
TI  - Recombinant subunit vaccines: potentials and constraints.
AB  - Recombinant DNA techniques have enormous potential for the development of
      inexpensive, safe and efficacious vaccines for the aquaculture industry. Aside
      from rationally attenuated pathogens, two broad categories of recombinant
      vaccines have been described. The first are so-called "vectored" vaccines, which
      consist of either viral or plasmid expression vectors harbouring genes for
      protective antigens from a given pathogen. The second are recombinant subunit
      antigens produced using heterologous protein expression systems. Less onerous
      from a regulatory standpoint, recombinant subunit vaccines generate strong
      antibody responses in recipient animals when administered parenterally with
      adjuvant-containing formulations. This approach is nevertheless constrained by
      the fact that low-cost systems for protein expression (especially E. coli, but
      also yeast) often generate misfolded or incorrectly processed membrane antigens
      that fail to protect, while more complex insect and mammalian tissue culture
      cells are prohibitively expensive from a production standpoint. Furthermore,
      subunit antigens generate less than optimal mucosal and cytotoxic T-cell
      responses, the last two of which are especially important for the clearance of
      intracellular pathogens. Fortunately, these constraints are now being overcome
      through the use of new generation adjuvants and delivery systems that enhance
      immunogenicity, as well as new expression systems for the production of viral and
      protozoan membrane antigens.

PMID- 15962479
TI  - Development of a subunit vaccine for infectious pancreatic necrosis virus using a
      baculovirus insect/larvae system.
AB  - Various attempts to develop a vaccine against infectious pancreatic necrosis
      virus (IPNV) have not yielded consistent results. Thus, at present, no commercial
      vaccine is available that can be used with confidence to immunize fry of salmon
      and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp
      strain and expressed all structural protein genes in insect cells and larvae
      using a baculovirus expression system. Green fluorescent protein was also
      coexpressed as a reporter molecule. High yields of IPNV proteins were obtained
      and the structural proteins self assembled to form virus-like particles (VLPs).
      We tested the immunogenicity of the putative VLP antigen in immersion vaccine
      experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and
      by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using
      an oil adjuvant formulation. Rainbow trout were challenged by immersion using
      either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination,
      while Atlantic salmon were bath challenged with Sp strain after two months, after
      parr-smolt transformation. In the rainbow trout fry challenged two weeks post
      immunization, cumulative mortality rates three weeks post challenge were 14 % in
      the fry that had received the highest dose versus 8 % in the control groups. No
      indication of protection was seen in repeated trials using a lower dose of
      antigen and challenge three weeks post-immunisation. The cumulative mortality
      rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post
      challenge was lower (56%) than in the control fish (77%), showing a dose-response
      pattern.

PMID- 15962480
TI  - An oral delivery system for recombinant subunit vaccine to fish.
AB  - Oral vaccination is considered as the most desirable method for immunizing fish
      because it is non-stressful, user-friendly and is capable of easy administration
      to large numbers of fish. However, many publications have indicated that the
      current oral vaccines still lack the desired efficacy. Here we reported on an
      oral vaccine method to deliver recombinant subunit vaccine based on the food
      chain of fish, in that live Artemia nauplii are encapsulated with recombinant
      bacteria containing the antigen. The feasibility and efficacy of this method for
      delivering protein antigen was tested in a zebrafish model, where immunisation
      took place through feeding Artemia encapsulated with recombinant E. coli. By this
      oral vaccine method the antigen could be delivered to the hindgut as confirmed by
      immuno-histochemistry, and its efficacy was demonstrated by the ability to
      protect vaccinated fish significantly from a direct injection of a native
      Pseudomonas exotoxin and bacterial pathogen. Combined with the recombinant
      technology for producing desired protein antigens, this oral vaccine delivery
      method provides the capacity to deliver a variety of different antigens,
      including the option for delivery of multivalent vaccines by the oral route.

PMID- 15962481
TI  - The place of marker vaccines in control and eradication of animal diseases-
      aspects of comparative interest.
AB  - Smallpox is the first viral infection to have been eradicated world-wide. This
      remarkable success is due to several factors including the availability of an
      efficacious vaccine and the absence of a wildlife reservoir. The only animal
      virus disease sharing these characteristics is rinderpest, for which there are
      several efficacious vaccines. Other animal viral infections do not share the same
      characteristics, either due to the lack of an efficacious vaccine (African swine
      fever), or to the existence of wildlife reservoirs such as the wild boar for
      classical swine fever, the African buffalo for foot-and-mouth disease, bats for
      lyssavirus infections, etc. These diseases are more prone to regional elimination
      than a complete worldwide eradication. Two methods are used to eliminate an
      animal viral infection, either vaccination or the strict application of hygienic
      measures including stamping out and incineration, or the combination of both
      methods. Public opinion is more and more concerned about stamping out, even when
      necessary such as when dealing with emerging zoonoses. On the other hand,
      generalised vaccination (i.e. against foot-and-mouth disease, classical swine
      fever, etc.) may be discontinued despite its efficacy, for macro-economical
      reasons. The solution may come from the use of marker vaccines associated with
      companion diagnostic tests to make a distinction between infected and immunised
      animals by serological examination. Current control and eradication programmes
      against these and other diseases, the role of marker vaccines, and the
      limitations of such programmes are being discussed.

PMID- 15962482
TI  - Use of Arthrobacter davidanieli as a live vaccine against Renibacterium
      salmoninarum and Piscirickettsia salmonis in salmonids.
AB  - Arthrobacter davidanieli (proposed species nomenclature) is a non-pathogenic Gram
      variable bacterium related to, but taxonomically distinct from, Renibacterium
      salmoninarum, the aetiological agent of bacterial kidney disease (BKD). We have
      demonstrated that vaccination with live A. davidanieli is effective against BKD
      in Atlantic salmon (Salmo salar) showing above 80 relative percent survival in
      experimental challenge trials. Good protection was also demonstrated in long-term
      field trials where Atlantic salmon were naturally exposed to R. salmoninarum
      challenge until 23 months after vaccination. The same vaccine, which is licensed
      in Canada against BKD has also proved effective in reducing mortality from
      experimental challenge of coho salmon (Oncorhynchus kisutch) with Piscirickettsia
      salmonis, the causative agent of piscirickettsiosis. Under field conditions in
      Chile, use of the vaccine led to a significant reduction in piscirickettsiosis
      mortality in coho salmon over 10 months following sea transfer. The vaccine
      strain is unique in that it is the first live organism to be licensed as a
      vaccine for use in aquaculture. Potential mechanisms of protection against the
      two taxonomically disparate pathogens are discussed.

PMID- 15962483
TI  - Overview of recent DNA vaccine development for fish.
AB  - Since the first description of DNA vaccines for fish in 1996, numerous studies of
      genetic immunisation against the rhabdovirus pathogens infectious haematopoietic
      necrosis virus (IHNV) and viral haemorrhagic septicaemia virus (VHSV) have
      established their potential as both highly efficacious biologicals and useful
      basic research tools. Single small doses of rhabdovirus DNA constructs provide
      extremely strong protection against severe viral challenge under a variety of
      conditions. DNA vaccines for several other important fish viruses, bacteria, and
      parasites are under investigation, but they have not yet shown high efficacy.
      Therefore, current research is focussed on mechanistic studies to understand the
      basis of protection, and on improvement of the nucleic acid vaccine applications
      against a wider range of fish pathogens.

PMID- 15962484
TI  - Critical assessment of regulatory standards and tests for fish vaccines.
AB  - Within the European Economic Area (EU member states plus Norway, Iceland and
      Liechtenstein), veterinary vaccines must comply with EU regulations and relevant
      monographs of the European Pharmacopoeia. Since 1996, three European monographs
      specific for fish have been adopted; concerning oil-adjuvanted, injectable
      vaccine for salmonids against furunculosis, as well as bacterins against
      classical vibriosis (Listonella anguillarum) or cold-water vibriosis (Vibrio
      salmonicida) in salmonids. The regulatory requirements laid down in these
      monographs include the use of seronegative fish for in vivo safety testing;
      conduct of vaccination trials in which experimental challenge is administered by
      injection, and minimum relative protection to be achieved at a given level of
      control mortality. Several aspects of these requirements are being questioned.
      This concerns the relevance of injection challenge methods as opposed to
      waterborne challenge; the validity of relative protection assessed at 60 %
      control mortality (RPS6) as compared to protection calculated at the endpoint of
      mortality (RPSendpoint), and poor test power due to low numbers of fish per
      treatment group. There is a strong need for future efforts to refine the methods
      for documentation and testing of fish vaccines, and to assure their suitability
      for the intended purpose.

PMID- 15962485
TI  - European Pharmacopoeia (EP), USDA and MAFF standards--will they ever be
      harmonised under the VICH umbrella?
AB  - Harmonisation of standards can have benefits for both users and manufacturers of
      vaccines. It also helps regulatory authorities when products are assessed to have
      a uniform standard in different regions. The first priority for harmonisation has
      to be the elimination of duplicate testing for the same purpose, for example
      tests for safety, immunogenicity and batch potency. A further priority is to
      harmonise batch-testing requirements first, since duplication of testing affects
      production batches. Fish vaccines present particularities as far as harmonisation
      between regions is concerned because of geographical, climatic and other factors.
      A commitment from regulatory authorities and manufacturers is a precondition for
      harmonisation. The different parties should commit themselves to harmonisation
      within a reasonable time and to implementing their decisions promptly. When there
      is a commitment on the part of all participants to work together in developing
      common science-based regulatory standards, then the optimal conditions exist.
      Harmonisation is time-consuming and costly but in the end the benefits can no
      doubt exceed the investment. Harmonisation also needs a forum since the present
      terms of reference of regulatory and standardisation bodies do not cover this.
      The only forum at present is the International Cooperation on Harmonization of
      Technical Requirements for Registration of Veterinary Products (VICH), which is a
      tripartite activity involving the European Union, Japan and the U.S.A. Before
      deciding to propose inclusion in the VICH programme, a preliminary study should
      be carried out to assess the benefits expected, the obstacles to harmonisation
      and the feasibility of achieving a satisfactory result. In the framework of VICH,
      there have been some successful harmonisation projects for veterinary vaccines:
      residual formaldehyde determination, and residual moisture determination. A
      harmonised proposal for mycoplasma testing is now available for public comment.
      Work on extraneous agents testing for avian and mammalian viral vaccines is well
      advanced.

PMID- 15962486
TI  - Regulatory constraints as seen from the pharmaceutical industry.
AB  - In Chile, Canada, Europe, Japan, and the USA, which are the main geographical
      areas for fish farming of high value fish such as salmonids, sea bass, sea bream,
      yellowtail and catfish, vaccination has been established as an important method
      for the prevention of infectious diseases. To make new vaccines available to the
      fish farming industry, pharmaceutical companies must comply with the regulatory
      framework for licensing of fish vaccines, which in recent years has become more
      regulated. Considerable scientific and regulatory skills are thus required to
      develop, document and license vaccines in accordance with the requirements in the
      different geographical areas. International co-operation to harmonise
      requirements for the licensing documentation is ongoing. Even though there are
      obvious benefits to the pharmaceutical industry from the harmonisation process,
      it may sometimes impose unreasonable requirements. The regulatory framework for
      fish vaccines clearly has an impact on the time for bringing a new fish vaccine
      to the market. Several hurdles need to be passed to complete the regulatory
      process, i.e. obtain a licence. Fulfilment of the rather detailed and extensive
      requirements for documentation of the production and controls, as well as safety
      and efficacy of the vaccine, represent a challenge to the pharmaceutical
      industry, as do the different national and regional licensing procedures. This
      paper describes regulatory constraints related to the documentation, the
      licensing process, the site of production and the continuing international
      harmonisation work, with emphasis on inactivated conventional fish vaccines.

PMID- 15962487
TI  - Vaccination and consumer perception of seafood quality.
AB  - Unlike other segments of international food production, finfish aquaculture has
      so far not been associated with major food scandals. However, because of
      increased focus on food safety, the seafood industry and associated businesses
      have to respond to and document all aspects related to their products and
      processes. Consumers have a right to know, and need knowledge and information to
      be able to make qualified choices. In aquaculture good management and
      environmental attention is essential for both product quality and economic
      sustainability. One of the main challenges in all farming activities is efficient
      fish health management, which is crucial for maintaining and further developing
      the industry. In all biological production, and also in aquaculture, diseases
      have been, are, and will continue to present a challenge. When dealing with
      disease incidents, environmental, ethical, biological and economic issues must be
      taken into account. In animal health management there is a common understanding
      that prevention is better than treatment, so also in aquaculture. In many
      segments of industrial fish farming, vaccines have proved a good management tool
      to control diseases and to reduce both mortality and the use of
      chemotherapeutics. As seen in a recent Norwegian consumer survey, this might
      unfortunately look somewhat different from a consumer point of view. The
      perception of vaccines as foreign substances, visible vaccine lesions or pigment,
      words about genetically produced vaccines, and a general lack of knowledge may
      fuel scepticism. Even when experts are giving good and well-documented
      information, consumers still stick to their original perception of food,
      including seafood. Given this background, this papers discusses the aquaculture
      industry's priorities regarding vaccines and vaccination strategies, and its
      information policy towards the customer.

PMID- 15962488
TI  - The choice of disease control strategies to secure international market access
      for aquaculture products.
AB  - Since production from capture fisheries cannot meet the demands of exports,
      aquaculture has subsequently played a major role in securing the raw materials
      for the world's food industries. Aquaculture has rapidly developed from extensive
      systems to semi-intensive, intensive and super-intensive systems. This has
      introduced the use of chemicals and drugs into the systems, which cause residual
      problems in the products. In the developed world, food safety has become a major
      issue of concern. The world market now demands healthy aquaculture products from
      farm to table. To achieve these requirements and to keep their markets, countries
      involved in aquaculture have implemented control measures such as farm licensing,
      code of conduct for sustainable aquaculture, hazard analysis and critical control
      point (HACCP) and good aquaculture practice. However, infectious diseases in
      aquaculture are of major concern to the industry and are typically controlled by
      eradication of the pathogen, treatment with antibiotic or chemotherapeutics,
      and/or by preventative measures such as the use of probiotics or vaccines. To
      limit the use of chemicals and antibiotics, good farm management is highly
      recommended. In terms of treatment, chemicals and antibiotics should be evaluated
      to establish recommended doses and withdrawal periods, otherwise alternative
      treatments should be developed. Environmentally-friendly probiotics have been
      introduced to aquaculture practice in the last decade to replace pathogenic
      bacteria with beneficial bacteria transient in the gut. Micro-organisms have also
      been prepared for the purpose of biocontrol and bioremediation. The application
      of probiotic, biocontrol and bioremediation seem promising; however considerable
      efforts of further research in terms of food and environmental safety are needed.
      Vaccination has proved highly effective in controlling diseases in the salmon
      industry mainly in Europe, America and Japan. In other Asian countries, this
      practice seem to be slower to develop due to differences in the aquaculture
      systems used and the economic value of the fish species farmed. Because shrimp
      farming is a large industry in this region, much effort has been put into
      developing a vaccine for viral diseases of shrimp. The efficacy of those vaccines
      remains inconclusive. Immunostimulants are another option developed for use in
      the shrimp industry in the region; however their efficacy also remains unclear.

PMID- 15962489
TI  - Vaccines for the control of reproduction--status in mammals, and aspects of
      comparative interest.
AB  - The objective of producing vaccines which target elements of the reproductive
      system to control fertility has been pursued for many years. Of the many targets
      for such vaccines, several sperm-associated antigens have been proposed for
      antibody-mediated intervention before fertilization but the very abundance of
      antigen to be neutralized has been a barrier. Zona pellucida antigens associated
      with the surface of the oocyte have also been targeted and used successfully for
      control of 'wild' elephant populations but worries concerning
      immunopathologically-mediated tissue damage have been mooted. Vaccines using
      human chorionic gonadotropin (hCG) which is required for the implantation and
      maintenance of the fertilized egg, although of interest for the development of
      fertility control in human populations, has no relevance in the context of the
      present conference because external fertilization of fish eggs is independent.
      The pathways by which gonadotropin-releasing hormone (GnRH) secreted by the
      hypothalamus promote release of luteinizing (LH) and follicle-stimulating hormone
      (FSH) which govern the physiological maturation and maintenance of the
      reproductive organs, provide many targets for immunological intervention. Most
      consistent success has been reported using GnRH-based vaccines which are
      immunosterilizing in a variety of mammalian species such as pigs, rodents and
      white-tailed deer. The fact that the structure of the decapeptide, GnRH, has been
      maintained over so many years of evolution and been conserved across so many
      animal species, encourages the view that a strategy for control of sexual
      maturation in fish based upon stimulation of GnRH antibodies may well prove to be
      a practical proposition, provided the formulation of an appropriate highly
      immunogenic vaccine can be achieved.

PMID- 15962490
TI  - [The emergency services strike: an impossible task].

PMID- 15962491
TI  - [Without delay we should invent urological surgery for tomorrow].

PMID- 15962492
TI  - [CRP in the management of bacterial infections in emergency].
AB  - OBJECTIVES: To assess the interest of measuring CRP in emergency for diagnosing
      bacterial infections and making decisions about antibiotics and to compare its
      practical usefulness with clinicians' conclusions. METHODS: Systematic CRP
      measurements in 80 consecutive patients admitted to emergency ward with possible
      bacterial infection. RESULTS: were not transmitted to the physician in charge.
      Patients' files were analyzed retrospectively in two phases. In phase 1, two
      senior physicians assessed the diagnosis and need for antibiotics on the basis of
      the admission (emergency unit) files. In phase 2, a panel of experts examined the
      complete files (including discharge notes) to determine the likelihood of
      infection (obvious or probable, unlikely or excluded) and appropriateness of
      emergency antibiotics. Their recommendations were used as the standard, against
      which the usefulness of the laboratory indicators (including CRP) and decisions
      of the emergency physicians were assessed. ROC curves were used to determine
      threshold values for CRP and body temperature. We then calculated the
      sensitivity, positive predictive value and negative predictive value of these
      cutoffs and compared them with those for the phase 1 clinician recommendations.
      RESULTS: The study included 76 patients (mean age: 74 years): 28 presented
      obvious or possible infections and 21 required emergency antibiotic therapy. Mean
      leukocyte values did not differ between groups. For diagnosis, the threshold
      value of CRP was 85 mg/L and of body temperature 37.8 degrees C; for prescribing
      antibiotics, the values were 130 mg/L and 38 degrees C, respectively. The
      sensitivity, specificity, negative and positive predictive values of CRP were,
      respectively, 79, 81, 76, and 83% for diagnosis of bacterial infection and 71,
      71, 48 and 87% for prescription of an emergency antibiotic. These values were
      lower than those of clinician's conclusions. CONCLUSION: Because of the
      variability in the thresholds used in its interpretation, the lack of
      specificity, and its poor predictive value for treatment decisions, CRP is of
      little interest in the diagnosis and treatment of patients with bacterial
      infections in intensive care. The cost generated by this examination is therefore
      not justified.

PMID- 15962493
TI  - [Emergency room deaths: 3-month retrospective analysis].
AB  - OBJECTIVES: Determine the characteristics of patients who died in the emergency
      unit and assess the number for whom care was limited or withdrawn. METHODS: A 3
      month single-center retrospective study of all the patients who died in the
      emergency room. Bivariate analysis was used to compare the clinical
      characteristics of patients who died despite maximum care (MC) with those for
      whom care was limited (LC). RESULTS: 84 patients died during the study period: 48
      men and 36 women (mean age: 73 +/- 18 years). Half had normal mobility (43
      patients, 50%), and 35 (40%) lived at home. Nearly all (72 patients, 72%) had a
      severe chronic disease. In descending order, death was ascribed to neurological
      (n = 22, 24%), cardiac (n = 14, 15%), septic (n = 13, 14%) and respiratory (n =
      9, 10%) causes. The decision was made to limit or stop active care for 73
      patients (84%) and recorded in 48 case files (55%). The principal differences
      between patients receiving MC and LC were respectively C and D Knaus
      classification and their age. CONCLUSION: Death is frequent in emergency units
      and often strikes elderly patients with impaired mobility and severe chronic
      diseases. The decisions to limit or stop active care are the predominant direct
      cause, but their modalities warrant further exploration in a prospective study.

PMID- 15962494
TI  - [Harmonizing indications for emergency radiological examinations for adults].
AB  - INTRODUCTION: The "Collegiale des radiologistes" of the Paris public hospital
      system (Assistance Publique-Hopitaux de Paris, AP-HP) has participated since 1998
      in a collaborative quality improvement program for the 49 radiology departments.
      They work together with the AP-HP college of emergency physicians on one part of
      this program, which focuses on emergency radiologic work-ups. Analysis of the
      dysfunctions in this sector underlined the lack of agreement between clinicians
      and radiologists on the examinations required. OBJECTIVE: The aim of this project
      was to establish operational and consensual guidelines for physicians,
      radiologists and emergency teams for the use of diagnostic radiology in emergency
      situations in adults. METHOD: The working group of radiologists and emergency
      physicians drafted this document, largely from documentary sources. A large panel
      of physicians validated the draft during successive review sessions, and the two
      colleges then approved them. RESULTS: The guidelines are presented in 3 columns:
      clinical situations, quality aims (type of imaging, time within which the
      examination should be performed) and comments. The clinical situations were
      regrouped by anatomical area or system: head, neck, thorax, heart, gynecology,
      abdomen, urinary, non-traumatic bone and spine disorders, multiple trauma, and
      isolated trauma of the spine and limbs and of the head, trunk, abdomen, and
      pelvis. CONCLUSION: These guidelines based on consensus within the institution
      make it possible to harmonize the requests for and practices of radiologic
      examinations in emergency situations. Their implementation is an integral part of
      the ongoing development of operating agreements between the radiology and
      emergency departments.

PMID- 15962495
TI  - [Primary hydatid cyst of the thyroid, an unusual localisation of hydatidosis].
AB  - INTRODUCTION: Echinococcus granulosus, responsible for hydatidosis, most often
      lodges in the liver and lungs, but is found in other organs of the body in 10% of
      cases. CASE: A painless, left cervical tumefaction suddenly developed in a 28
      year-old Portuguese man. After thyroid lobectomy with isthmusectomy, the
      pathology findings led to the diagnosis of hydatidosis. DISCUSSION: The thyroid
      is a rare location for a hydatid cyst. Diagnosis can be difficult and fine-needle
      aspiration cytology is not usually helpful. Treatment requires surgical excision,
      and administration of benzimidazole derivatives to prevent recurrence.

PMID- 15962496
TI  - [A urachus cyst revealing a torpid Crohn's disease in a young adult with chronic
      fever].
AB  - INTRODUCTION: This case report describes a rare situation in which a
      superinfected cyst of the urachus complicated initially unknown and inactive
      Crohn's disease. CASE: A 21-year-old man presented a chronic fever finally
      attributed to a superinfected urachal cyst. Six months after ablation of the
      cyst, progressive Crohn's disease was diagnosed. DISCUSSION: The association of
      Crohn's disease and a superinfected urachal cyst is extremely rare. The case
      reported here is original in two aspects: the slowly progressive Crohn's disease
      was diagnosed after its complication; the superinfection developed through local
      bacterial translocation (ileal loop adjacent to the urachal cyst).

PMID- 15962497
TI  - [Macrophage activation syndrome after treatment with infliximab for fistulated
      Crohn's disease].
AB  - INTRODUCTION: Macrophage activation syndrome has never been reported as an
      adverse effect of infliximab. CASE: Treatment with infliximab was prescribed for
      a 37-year-old man with fistulated Crohn's disease unresponsive to azathioprine.
      Three months after the last injection, he developed macrophagic activation
      syndrome, with febrile pancytopenia, hyperferritinemia, hypertriglyceridemia and
      an activated cephalin time twice the control level. DISCUSSION: Elimination of
      the known causes of macrophage activation syndrome suggests it is related to the
      infliximab treatment, but its pathogenesis remains a mystery.

PMID- 15962498
TI  - [Vasoplegic shock and myocardial infarction during administration of iloprost].
AB  - INTRODUCTION: The association of vasoplegic shock and myocardial infarction in a
      patient under iloprost treatment for critical ischemia of the lower limbs has not
      previously been reported. OBSERVATION: A 56 year-old man suffering from type 2
      diabetes, hypertension and dyslipidemia developed critical ischemia of the right
      leg and was treated with iloprost. On the 19th day of infusion, he developed a
      vasoplegic shock with myocardial infarction. The shock resolved and he recovered
      from the infarction. DISCUSSION: This case report indicates the need for
      reinforced blood pressure and electrocardiographic monitoring in diabetes
      patients treated with iloprost.

PMID- 15962499
TI  - [Mycobacterium marinum tenosynovitis of the abductors].
AB  - INTRODUCTION: Infection with Mycobacterium marinum is rare and usually produces
      cutaneous lesions. We report here two cases of tenosynovitis of abductor muscles.
      CASE: The first case presented isolated involvement of the abductors of the left
      thumb, and the second the abductors of the middle finger. In both cases, the
      bacteriological examinations found M. marinum. Antibiotic therapy for three
      months with rifampin and clarithromycin cured the infection. DISCUSSION: These
      cases of tenosynovitis followed deep inoculation. A mycobacterial infection
      should be considered in cases of synovitis, especially when limited to an area of
      the hand in patients without other rheumatic disorders.

PMID- 15962500
TI  - Systemic adverse effects of topical ocular treatments.
AB  - Some eyedrops, gels or ointments may cause adverse effects as serious as those
      observed with systemic therapies. Because of their relatively poor penetration
      into eye tissue, ophthalmic drugs usually contain high concentrations of their
      active ingredient. Asking patients about these drugs to prevent interactions is
      useful when prescribing a new systemic treatment. Conversely, it is advisable to
      ask about ophthalmic drugs during the etiological investigation of possible
      iatrogenic effects.

PMID- 15962501
TI  - [Choice of a dialysis method for patients with kidney failure].
AB  - The principal options for treatment of end-stage renal disease are hospital, out
      center, self-or home hemodialysis or continuous ambulatory or automated
      peritoneal dialysis. Hemodialysis and peritoneal dialysis were long considered
      competitive methods, but they have become complementary and the same patient can
      use them successively at different life stages. The choice of technique usually
      depends on family, personal, social and work factors, rather than the medical
      situation. The healthcare team provides guidance to the patient in making this
      choice. The choice of treatment is optimal when the referral is early.

PMID- 15962502
TI  - [Transitional cell carcinoma of the upper urinary tract new concepts in
      management].
AB  - Transitional cell carcinomas of the upper urinary tract (UUT-TCCs) are rare: they
      account for approximately 5% of all urothelial carcinomas. 30% of patients with
      UUT-TCC have a history of bladder TCC, but fewer than 2% of patients with bladder
      TCC have UUT-TCC. Tumor microsatellite instability (MSI) is an indicator of the
      clonal expansion of neoplasms; it was first identified in tumors from patients
      with hereditary non-polyposis colorectal carcinoma (HNPCC). UUT-TCC occurs in 5%
      of patients with HNPCC. High-frequency microsatellite instability is present in
      almost 20% of cases of sporadic UUT-TCC. In cases of UUT-TCC with high-frequency
      MSI, hereditary cancer must be sought, especially if the patient is younger than
      60 years or has a personal or family history of an HNPCC-related cancer: such
      patients should undergo DNA sequencing for the MSH2 gene germline mutation.
      Invasive UUT-TCC has a poor prognosis. 5-year survival is less than 50% for stage
      T2-T3 tumors and less than 10% for T4 or N+/M+ tumors. The main prognostic
      factors are age and tumor stage and grade. High-frequency MSI is a positive
      prognostic factor, especially in patients younger than 70 years with T2/T3/N0-M0
      tumors.

PMID- 15962503
TI  - [Paget's disease, workup and monitoring].
AB  - Paget's disease is a progressive bone disease, characterized by bone hypertrophy
      and increased bone resorption. The pain and deformity that characterize its
      clinical course are not simple to assess, but it has a characteristic
      radiographic appearance. In most cases, treatment can be monitored through
      biological markers of bone turnover. Total alkaline phosphatase is the best
      marker and measurement of collagen breakdown products is useful in difficult
      cases. The goal of treatment is the normalization of these biological markers, to
      prevent complications of the disease.

PMID- 15962504
TI  - [Paget's disease and its therapeutic management].
AB  - Bisphosphonates, potent anti-osteoclastic agents, are nowadays the first-line
      therapy for Paget's disease of bone. Solid evidence about efficacy and the
      risk/benefit ratio favor tiludronate and risedronate for oral administration and
      pamidronate for intravenous administration. Treatment is always intermittent,
      with the frequency of therapeutic sequences depending on the specific drug and
      the quality and duration of response. Treatment response is assessed by the
      extent of the reduction of biochemical markers of bone turnover, especially
      plasma total alkaline phosphatase. The goal of the treatment is to induce full
      remission, that is, normal levels of alkaline phosphatase. Bisphosphonates should
      be used in all patients with bone involvement that might create long-term
      articular (arthropathy) or neurologic (compression) complications. This
      aggressive strategy is the most likely to provide effective prevention of
      complications in the long term.

PMID- 15962505
TI  - [Nodular dermohypodermatitis of the right arm].

PMID- 15962506
TI  - Dynamics of CNS barriers: evolution, differentiation, and modulation.
AB  - (1) Three main barrier layers at the interface between blood and tissue protect
      the central nervous system (CNS): the endothelium of brain capillaries, and the
      epithelia of the choroid plexus (CP) and the arachnoid. The classical work on
      these barriers in situ until the 1970s laid the foundations for modern
      understanding. Techniques for brain endothelial cell isolation and culture
      pioneered by Ferenc Joo in the 1970s opened up new fields of examination,
      enabling study of mechanisms at the cellular and molecular level. (2) Astrocytic
      glial cells are closely associated with the brain endothelial barrier. During
      evolution the barrier appears to have shifted from the glial to the endothelial
      layer, in parallel with the increasing importance of the microvasculature and its
      regulation. Vestiges of the barrier potential of glia remain in the modern
      mammalian CNS. (3) Evolutionary evidence suggests that the advantage derived from
      ionic homeostasis around central synapses was the major selective pressure
      leading to refinement of CNS barrier systems. This is one element of the modern
      'multitasking' barrier function. (4) While epithelia are constitutively able to
      form barriers at appropriate interfaces, the 'default' condition for endothelia
      is more leaky; inductive influences from associated cells especially astrocytes
      are important in generating the full blood-brain barrier (BBB) phenotype in brain
      capillaries. The underlying mechanisms are being elucidated at the molecular and
      genomics level. (5) The barrier layers of the nervous system can be modulated by
      a number of receptor-mediated processes, involving several signal transduction
      pathways, both calcium dependent and independent. Some agents acting as
      'inducers' in the long term can act as 'modulators' in the short-term, with some
      overlap of signaling pathways. Modulating agents may be derived both from the
      blood and from cells associated with cerebral vessels. Less is known about the
      modulation of the CP. (6) The challenge for the next era of CNS barrier studies
      will be to apply new knowledge from proteomics and genomics to understanding the
      in vivo condition in physiology and pathology.

PMID- 15962507
TI  - In search of the astrocytic factor(s) modulating blood-brain barrier functions in
      brain capillary endothelial cells in vitro.
AB  - (1) The blood-brain barrier (BBB) is formed by brain capillary endothelial cells
      (ECs). There are various cell types, in particular astrocytes, but also pericytes
      and neurons, located in close vicinity to the capillary ECs which may influence
      formation and function of the BBB. Based on this consideration, this paper
      discusses various aspects of the influence of the surrounding cells on brain
      capillary ECs with special focus on the role of astrocytes. (2) Based on the
      morphology of the BBB, important aspects of brain EC functions are summarized,
      such as transport functions and maintenance of low paracellular permeability.
      Moreover, various facets are discussed with respect to the influence of
      astrocytes, pericytes, microglia, and neurons on the BBB. Data on the role of
      glial cells in the ontogenesis of the BBB are presented subsequently. The
      knowledge on this subject is far from being complete, however, these data imply
      that the neural/neuronal environment rather than glial cells may be of importance
      in the maturation of the barrier. (3) The role of glial cells in the induction
      and maintenance of the BBB is discussed under physiological as well as
      pathological conditions. Although the literature presents manifold evidence for a
      great variety of effects induced by astroglia, there are also many controversies,
      which may result from different cellular models and experimental conditions used
      in the respective studies. Numerous factors secreted by astrocytes have been
      shown to induce a BBB phenotype. On the molecular level, increased expression of
      barrier-relevant proteins (e.g., tight junction proteins) is documented in the
      presence of astrocyte-derived factors, and many studies demonstrate the
      improvement of physiological parameters, such as increased transendothelial
      resistance and decreased paracellular permeability, in different in vitro models
      of the BBB. Moreover, one has to take into account that the interaction of brain
      ECs and astrocytes is bi-directional, and that the other cell types surrounding
      the brain microvasculature also contribute to BBB function or dysfunction,
      respectively. (4) In conclusion, it is expected that the present and future
      research focused on molecular mechanisms and signaling pathways will produce new
      and exciting insights into the complex network of BBB regulation: the cornerstone
      is laid.

PMID- 15962508
TI  - Rat brain endothelial cell lines for the study of blood-brain barrier
      permeability and transport functions.
AB  - (1) In vitro models of the BBB have been developed from cocultures between
      bovine, porcine, rodent or human brain capillary endothelial cells with rodent or
      human astrocytes. Since most in vivo BBB studies have been performed with small
      laboratory animals, especially rats, it is important to establish a rat brain
      endothelial (RBE) cell culture system that will allow correlations between in
      vitro and in vivo results. The present review will constitute a brief description
      of the best characterized RBE cell lines (RBE4, GP8/3.9, GPNT, RBEC1, TR-BBBs and
      rBCEC4 cell lines) and will summarize their recent and important contribution to
      our current knowledge of the BBB transport functions and permeability to blood
      borne solutes, drugs, and cells. (2) In most cases, primary cultures of RBE cells
      were transduced with an immortalizing gene (SV40 or polyoma virus large T-antigen
      or adenovirus E1A), either by transfection of plasmid DNA or by infection using
      retroviral vectors. In one case however, the conditionally immortalized TR-BBB
      cell line was derived from primary cultures of brain endothelial cells of SV40-T
      expressing transgenic rats. (3) All cell lines appear to have an endothelial
      morphology. The absence of foci formation would mean that the cells are not
      transformed. The endothelial origin is shown by the expression of Factor VIII
      related antigen. Immortalized RBE cells express all the enzymes and transporters
      that are considered as specific for the blood-brain barrier endothelium, with
      similar characteristics to those expected from in vivo analyses, but at a
      significantly lower level. Some RBE cell lines are responsive to astroglial
      factors, such as RBE4 cells, rBEC4, and TR-BBB cells. None of the immortalized
      RBE cell lines appear to generate the necessary restrictive paracellular barrier
      properties that would allow to use them in transendothelial permeability
      screening. (4) RBE cell lines have been used to demonstrate that transporters
      such as organic cation transporter/carnitine transporter, serotonin transporter,
      and the ATA2 system A isoform are expressed in rat brain endothelium. When the
      transporter is shown to be expressed with the same properties in the immortalized
      RBE cells as in vivo, regulation studies may be initiated even if the transporter
      is down-regulated. Pharmacological applications have been proposed with well
      characterized transporters such as monocarboxylic acid transporter-1, large
      neutral amino acid tansporter-1, nucleoside carrier systems, and P-glycoprotein.
      RBE cell monolayers have also been used to investigate the mechanism of the
      transendothelial transport of large molecules, such as immunoliposomes or
      nanoparticles, potentially useful as drug delivery vectors to the brain. (5) RBE4
      and GP8 cell lines have been extensively used to demonstrate that intercellular
      adhesion molecule-1 (ICAM-1) engagement in brain endothelial cells triggers
      multiple signal transduction pathways. Using functional assays, it was
      established that ICAM-1 signaling is intimately and actively involved in
      facilitating lymphocyte infiltration. (6) Several RBE cell lines have been
      described, which constitute tentative in vitro models of the rat BBB. The major
      limitation of these models generally appears to be due to their relatively high
      paracellular permeability to small molecules, thus limiting their use for
      permeability studies. The strategies developed for the production of these RBE
      cell lines will enable the characterization of still more efficient permeability
      models, as well as the immortalization of human brain endothelial cells.

PMID- 15962510
TI  - Effect of oxidative stress on the junctional proteins of cultured cerebral
      endothelial cells.
AB  - (1) There is increasing evidence that the cerebral endothelium and the blood
      brain barrier (BBB) plays an important role in the oxidative stress-induced brain
      damage. The aim of the present study was to investigate the role of
      interendothelial junctional proteins in the BBB permeability increase induced by
      oxidative stress. (2) For the experiments, we have used cultured cerebral
      endothelial cells exposed to hypoxia/reoxygenation or treated with the redox
      cycling quinone 2,3-Dimethoxy-1,4-naphthoquinone (DMNQ) in the presence or
      absence of glucose. The expression of junctional proteins and activation of
      mitogen activated protein kinases (MAPK) was followed by Western-blotting, the
      interaction of junctional proteins was investigated using coimmunoprecipitation.
      (3) Oxidative stress induces a downregulation of the tight junction protein
      occludin expression which is more pronounced in the absence of glucose.
      Furthermore, oxidative stress leads to disruption of the cadherin-beta-catenin
      complex and an activation of extracellular signal-regulated kinase (ERK1/2),
      which is more intense in the absence of glucose. (4) We have shown that one of
      the causes of the BBB breakdown is probably the structural alteration of the
      junctional complex caused by oxidative stress, a process in which ERK1/2 may play
      an important role.

PMID- 15962511
TI  - Impaired regulation of pH homeostasis by oxidative stress in rat brain capillary
      endothelial cells.
AB  - (1) Endothelial cells are permanently challenged by altering pH in the blood, and
      oxidative damage could also influence the intracellular pH (pH(i)) of the
      endothelium. Cerebral microvascular endothelial cells form the blood-brain
      barrier (BBB) and pH(i) regulation of brain capillary endothelial cells is
      important for the maintenance of BBB integrity. The aim of this study was to
      address the pH regulatory mechanisms and the effect of an acute exposure to
      hydrogen peroxide (H2O2) on the pH regulation in primary rat brain capillary
      endothelial (RBCE) cells The RBCE monolayers were loaded with the fluorescent pH
      indicator BCECF and pH(i) was monitored by detecting the fluorescent changes. (2)
      The steady-state pH(i) of RBCE cells in HEPES-buffer (6.83 +/- 0.1) did not
      differ significantly from that found in bicarbonate-buffered medium (6.90 +/-
      0.08). Cells were exposed to NH4CI to induce intracellular acidification and then
      the recovery to resting pH was studied. Half-recovery time after NH4Cl prepulse
      induced acid load was significantly less in the bicarbonate-buffered medium than
      in the HEPES-medium, suggesting that in addition to the Na+ / H+ exchanger, HCO3-
      / Cl- exchange mechanism is also involved in the restoration of pH(i) after an
      intracellular acid load in primary RBCE cells. We used RT-PCR-reactions to detect
      the isoforms of Na+ / H+ exchanger gene family (NHE). NHE-1 -2, -3 and -4 were
      equally present, and there was no significant difference in the relative
      abundance of the four transcripts in these cells. (3) No pH(i) recovery was
      detected when the washout after an intracellular acid load occurred in nominally
      Na+ -free HEPES-buffered medium or in the presence of 10 microM 5-(N-ethyl-N
      isopropyl)amiloride (EIPA), a specific inhibitor of Na+ / H+ exchanger. The new
      steady-state pH(i) were 6.37 +/- 0.02 and 6.60 +/- 0.02, respectively. (4) No
      detectable change was observed in the steady-state pH(i) in the presence of 100
      microM H2O2; however, recovery from NH4Cl prepulse-induced intracellular acid
      load was inhibited when H2O2 was present in 50 or 100 microM concentration in the
      HEPES-buffered medium during NH4Cl washout. These data suggest that H2O2 is
      without effect on the activity of Na+ / H+ exchanger at rest, but could inhibit
      the function of the exchanger after an intracellular acid load.

PMID- 15962509
TI  - Permeability studies on in vitro blood-brain barrier models: physiology,
      pathology, and pharmacology.
AB  - (1) The specifically regulated restrictive permeability barrier to cells and
      molecules is the most important feature of the blood-brain barrier (BBB). The aim
      of this review was to summarize permeability data obtained on in vitro BBB models
      by measurement of transendothelial electrical resistance and by calculation of
      permeability coefficients for paracellular or transendothelial tracers. (2)
      Results from primary cultures of cerebral microvascular endothelial cells or
      immortalized cell lines from bovine, human, porcine, and rodent origin are
      presented. Effects of coculture with astroglia, neurons, mesenchymal cells, blood
      cells, and conditioned media, as well as physiological influence of serum
      components, hormones, growth factors, lipids, and lipoproteins on the barrier
      function are discussed. (3) BBB permeability results gained on in vitro models of
      pathological conditions including hypoxia and reoxygenation, neurodegenerative
      diseases, or bacterial and viral infections have been reviewed. Effects of
      cytokines, vasoactive mediators, and other pathogenic factors on barrier
      integrity are also detailed. (4) Pharmacological treatments modulating
      intracellular cyclic nucleotide or calcium levels, and activity of protein
      kinases, protein tyrosine phosphatases, phospholipases, cyclooxygenases, or
      lipoxygenases able to change BBB integrity are outlined. Barrier regulation by
      drugs involved in the metabolism of nitric oxide and reactive oxygen species, as
      well as influence of miscellaneous treatments are also listed and evaluated. (5)
      Though recent advances resulted in development of improved in vitro BBB model
      systems to investigate disease modeling, drug screening, and testing vectors
      targeting the brain, there is a need for checking validity of permeability models
      and cautious interpretation of data.

PMID- 15962512
TI  - Pharmacological targeting of ICAM-1 signaling in brain endothelial cells:
      potential for treating neuroinflammation.
AB  - (1) The vasculature of the blood-brain barrier allows only comparatively few
      leukocytes to enter and survey the healthy central nervous system (CNS). However,
      during pathological CNS inflammation, the number of leukocytes adhering to and
      penetrating the CNS vasculature increases strongly. (2) Endothelial adhesion
      molecules do not only mediate firm adhesion of leukocyte to vascular beds but
      also trigger signaling cascades within the endothelial cell, which play a crucial
      role in modulating subsequent leukocyte diapedesis. (3) Signaling through
      endothelial intercellular adhesion molecule-1 (ICAM-1, CD54) has been shown to
      induce changes of the endothelial cytoskeleton, transcription, and
      interendothelial junctions, all of which may be important in modulating
      endothelial disposition to infiltrating leukocytes. Furthermore, a number of
      recent reports document that drugs interfering with endothelial ICAM-1 signaling,
      efficiently reduce leukocyte migration both in vitro and in animal models of CNS
      inflammation. (4) These approaches are novel in as much as they target vascular
      beds rather than the penetrating leukocytes. Since endothelial ICAM-1 signaling
      appears to differ between different vascular beds we propose that such compounds
      could potentially be used as exquisite drugs in the treatment of
      neuroinflammatory diseases.

PMID- 15962514
TI  - Human cerebral microvessel endothelial cell culture as a model system to study
      the blood-brain interface in ischemic/hypoxic conditions.
AB  - (1) Cerebral ischemia and reperfusion induce several changes on the endothelial
      cells at the microcirculatory level. (2) Vasogenic brain edema due to compromised
      blood-brain barrier, transformation of the endothelial cell surface from an
      anticoagulant to a procoagulant surface are important factors in the pathogenesis
      of ischemic stroke. (3) Release of prostaglandins, endothelin-1, complement
      proteins, and matrix metalloproteinase-9 by microvascular endothelial cells are
      other components in the complex mechanism of brain ischemia/hypoxia. (4)
      Ultrastructural studies documented the opened paracellular avenues in the course
      of vasogenic edema in different experimental models (5) Tight junctions of
      endothelial cells have been characterized with freeze fracture electron
      microscopy, and the process of transvesiculation was analyzed using rapid freeze
      and freeze substitution procedure before electron microscopy studies (6) In
      endothelial cell-culture experiments, we used rodent and later human brains. (7)
      Endothelial cells co-cultured with astroglia resulted in an elaborate tight
      junctional complex. (8) This co-culture technique becomes the basis of in vitro
      blood-brain barrier studies On endothelial cells of human brain origin, different
      regulatory factors found to be responsible for the complex mechanism of ischemic
      stroke.

PMID- 15962515
TI  - Interoperability conundrum: EMR implementation options go beyond core vendor and
      best of breed.

PMID- 15962513
TI  - Mechanisms of the blood-brain barrier disruption in HIV-1 infection.
AB  - (1) Alterations of brain microvasculature and the disruption of the blood-brain
      barrier (BBB) integrity are commonly associated with human immunodeficiency virus
      type 1 (HIV-1) infection. These changes are most frequently found in human
      immunodeficiency virus-related encephalitis (HIVE) and in human immunodeficiency
      virus-associated dementia (HAD). (2) It has been hypothesized that the disruption
      of the BBB occurs early in the course of HIV-1 infection and can be responsible
      for HIV-1 entry into the CNS. (3) The current review discusses the mechanisms of
      injury to brain endothelial cells and alterations of the BBB integrity in HIV
      infection with focus on the vascular effects of HIV Tat protein. In addition,
      this review describes the mechanisms of the BBB disruption due to HIV-1 or Tat
      protein interaction with selected risk factors for HIV infection, such as
      substance abuse and aging.

PMID- 15962516
TI  - Hired hands: farming out IT has friends and foes.

PMID- 15962517
TI  - Physician-led data sharing.

PMID- 15962518
TI  - Bridging the hospital-physician gap: with a three-part approach, CIOs can engage
      physicians in choosing and using technology.

PMID- 15962519
TI  - Transformation in the lab: hospitals are gearing up to automate.

PMID- 15962520
TI  - A 21st-century workforce solution: online bidding for nursing staff saves
      resources, improves recruitment and retention, and enhances care.

PMID- 15962521
TI  - The potential of WLANs: enterprise asset visibility begins with tracking
      equipment and ends with better patient care.

PMID- 15962522
TI  - Azacitidine.
AB  - Azacitidine (Vidaza; Pharmion), an inhibitor of DNA methylation, was approved by
      the US FDA for the treatment of myelodysplastic syndromes in May 2004. It is the
      first drug to be approved by the FDA for treating this rare family of bone-marrow
      disorders, and has been given orphan-drug status. It is also a pioneering example
      of an agent that targets 'epigenetic' gene silencing, a mechanism that is
      exploited by cancer cells to inhibit the expression of genes that counteract the
      malignant phenotype.

PMID- 15962523
TI  - Bevacizumab.
AB  - Bevacizumab (Avastin; Genentech/Roche), an antibody against vascular endothelial
      growth factor, was approved by the US FDA in February 2004 for the first-line
      treatment of metastatic colorectal cancer in combination with 5-fluorouracil
      based chemotherapy. It is the first approved agent to target tumour angiogenesis.

PMID- 15962524
TI  - Cetuximab.
AB  - Cetuximab (Erbitux; ImClone Systems/Bristol-Myers Squibb) is a monoclonal
      antibody that binds to the epidermal growth factor receptor, which is important
      in the growth of many cancers. In February 2004, it was granted accelerated
      approval by the US FDA for the treatment of metastatic colorectal cancer on the
      basis of tumour response rates in Phase II trials.

PMID- 15962525
TI  - Clofarabine.
AB  - Clofarabine (Clolar; Genzyme), a purine nucleoside antimetabolite, was granted
      accelerated approval by the US FDA for the treatment of paediatric patients with
      relapsed or refractory acute lymphoblastic leukaemia in December 2004. It is the
      first new drug for paediatric leukaemia to be approved in more than a decade, and
      the only one to receive approval for paediatric use before adult use.

PMID- 15962526
TI  - Erlotinib hydrochloride.
AB  - Erlotinib hydrochloride (Tarceva; OSI Pharmaceuticals/Genentech/Roche), a member
      of a class of targeted anticancer drugs that inhibit the activity of the
      epidermal growth factor receptor, was approved by the US FDA in November 2004 for
      the treatment of advanced non-small-cell lung cancer after failure of at least
      one prior chemotherapy regimen. It is the first such drug to demonstrate an
      increase in survival in Phase III trials in patients with advanced non-small-cell
      lung cancer.

PMID- 15962528
TI  - Oncology. Market indicators.

PMID- 15962527
TI  - Pemetrexed disodium.
AB  - In February 2004, pemetrexed disodium (Alimta; Eli Lilly), an anticancer drug
      that targets folate-dependent reactions that are essential for cell
      proliferation, became the first drug to be approved by the US FDA for the
      treatment of the rare cancer malignant pleural mesothelioma. Its accelerated
      approval for the second-line treatment of non-small-cell lung cancer followed in
      August 2004.

PMID- 15962529
TI  - Questions raised by the new CHUM.

PMID- 15962531
TI  - [Showcase of nurses' professional accomplishments].

PMID- 15962530
TI  - [Combined effect of Acticoat and VAC on wound healing].

PMID- 15962532
TI  - [Pneumococcal vaccine for all children].

PMID- 15962533
TI  - [Elimination of syringes and needles: a prickly subject].

PMID- 15962534
TI  - [France Paquet. The humanity of care, it's also that! Interview by Laurette
      Therrien].

PMID- 15962535
TI  - [Knowledge Transfer and Exchange Bureau].

PMID- 15962536
TI  - [Six nurses at Gonaives].

PMID- 15962537
TI  - Systems integration. The electronic records linchpin.

PMID- 15962538
TI  - Safety innovators put I.T. on the line.

PMID- 15962539
TI  - Effective I.T. budgeting takes practice.

PMID- 15962540
TI  - Is M.D. resistance an old chestnut?

PMID- 15962541
TI  - An Rx for reducing medication errors.

PMID- 15962542
TI  - Mobile images music to radiologists' ears.

PMID- 15962543
TI  - Readers' perspectives. Pharmacy benefit plans and pharmacies are moving
      expeditiously to support electronic prescriptions.

PMID- 15962544
TI  - Wound infections caused by Vibrio vulnificus and other marine bacteria.
AB  - Infections caused by Vibrio vulnificus were first reported in 1979 by Blake et
      al. of the US Centers for Disease Control. At that time described as a 'rare,
      unnamed halophilic lactose-fermenting Vibrio species', V. vulnificus has emerged
      as the most virulent foodborne pathogen in the United States with a
      hospitalization rate of 0.910 and a case-fatality rate of 0.390. It is in
      addition a significant cause of potentially life-threatening wound infections.
      Infections following ingestion of raw or undercooked seafood, commonly raw
      oysters, can lead to a primary septicaemia with a fatality rate of 50-60%. An
      unusual symptom, occurring in 69% of 274 cases reviewed by Oliver, is the
      development of secondary lesions, typically on the extremities, which are
      generally severe (often a necrotizing fasciitis) and require tissue debridement
      or amputation. These cases occur almost exclusively in males over the age of 50
      years. Interestingly, this gender specificity has been found to be due to the
      female hormone oestrogen, which in some manner provides protection against the
      lethal V. vulnificus endotoxin. Further, most cases occur in persons with certain
      underlying diseases which are either immunocompromising or which lead to elevated
      serum iron levels (e.g. liver cirrhosis, chronic hepatitis, haemochromatosis). V.
      vulnificus infections resulting in primary septicaemia have been extensively
      studied, and the subject of several reviews. This review concentrates on the
      wound infections caused by this marine bacterial pathogen, including the more
      recently described biotypes 2 and 3, with brief discussions of those caused by
      other marine vibrios, and the increasingly reported wound/skin infections caused
      by Mycobacterium marinum, Erysipelothrix rhusiopathiae, and Aeromnonas
      hydrophila.

PMID- 15962545
TI  - Epidemiology of pericardial effusions at a large academic hospital in South
      Africa.
AB  - The aim was to establish the prevalence of large pericardial effusions in the
      Western Cape Province of South Africa, and to determine the incidence of various
      types of effusions. A total of 233 patients presented with large pericardial
      effusions. Each patient underwent tests for HIV, sputum smear and culture, blood
      culture, blood biochemistry and serological testing. Tuberculous pericardial
      effusions were diagnosed according to pre-determined criteria. Eighty-four
      patients (36.1%) were found to be HIV positive; 81 of these (96.4 %) had
      tuberculous pericarditis. More than 65% of the study population was aged between
      15 and 39 years. The prevalence of HIV amongst unemployed individuals was 49.0%
      compared to 30.0% amongst employed individuals. Tuberculous pericarditis was the
      most common cause of pericardial effusions (69.5%, n=162). It was concluded that
      tuberculosis (TB) is a leading cause of pericarditis in this province of South
      Africa. The prevalence of TB confounded by HIV co-infection is steadily
      increasing, burdening the health-care facilities.

PMID- 15962546
TI  - Sensitivity of the Swedish statutory surveillance system for communicable
      diseases 1998-2002, assessed by the capture-recapture method.
AB  - To assess the sensitivity of the Swedish surveillance system, four notifiable
      communicable diseases in Sweden were examined during 1998-2002 with the two
      sources capture-recapture method, based on parallel clinical and laboratory
      notifications. The sensitivity (proportion of diagnosed diseases actually being
      notified) was highest for salmonellosis (99.9%), followed by meningococcal
      infection (98.7%), and tularaemia (98.5%). For penicillin-resistant pneumococci,
      introduced as a notifiable disease in 1996, the overall sensitivity was 93.4%-
      increasing from 86.5% in 1998 to 98.5% in 2002. The system benefited from
      parallel reporting, with a sensitivity of clinical and laboratory notifications
      alone (all diseases combined) of 91.6% and 95.9% respectively. The sensitivity of
      both clinical and laboratory notifications was markedly higher in counties using
      the national electronic reporting system, SmiNet. Thus, sensitivity was higher
      for diseases with a long tradition of reporting, and there is a run-in period
      after a new disease becomes notifiable.

PMID- 15962547
TI  - A model-adjusted space-time scan statistic with an application to syndromic
      surveillance.
AB  - The space-time scan statistic is often used to identify incident disease
      clusters. We introduce a method to adjust for naturally occurring temporal trends
      or geographical patterns in illness. The space-time scan statistic was applied to
      reports of lower respiratory complaints in a large group practice. We compared
      its performance with unadjusted populations from: (1) the census, (2) group
      practice membership counts, and on adjustments incorporating (3) day of week,
      month, and holidays; and (4) additionally, local history of illness. Using a
      nominal false detection rate of 5%, incident clusters during 1 year were
      identified on 26, 22, 4 and 2% of days for the four populations respectively. We
      show that it is important to account for naturally occurring temporal and
      geographic trends when using the space-time scan statistic for surveillance. The
      large number of days with clusters renders the census and membership approaches
      impractical for public health surveillance. The proposed adjustment allows
      practical surveillance.

PMID- 15962548
TI  - Risk factors of sexually transmitted infections among migrant and non-migrant
      sexual partnerships from rural South Africa.
AB  - In October 1998, cohorts of circular migrant men and their non-migrant sexual
      partners, and non-migrant men and their non-migrant sexual partners from rural
      South Africa were recruited and followed-up every 4 months until October 2001. At
      each visit, information on sociodemographic, sexual behaviour, sexually
      transmitted infections (STIs) and HIV was collected. In total, 553 individuals
      aged between 18 and 69 years were recruited. A man and his sexual partner(s) form
      a sexual partnership. Migration status, age, marital status, age at sexual debut,
      recent sexual partners and HIV status were found to be important determinants of
      STI. The risk of STI varies (sigma2 = 1.45, P < 0.001) significantly across
      sexual partnerships even after controlling for important determinants. The
      variance implies substantial correlation (0.59) between members of the same
      sexual partnership. Ignoring this correlation leads to incorrect inference.
      Migration contributes significantly to the spread of STIs. Community
      interventions of HIV/STI should target co-transmitter sexual partnerships rather
      than high-risk individuals.

PMID- 15962549
TI  - Outbreaks of gastroenteritis due to infections with Norovirus in Switzerland,
      2001-2003.
AB  - Viral infections, especially those with noroviruses are the most common cause of
      acute gastroenteritis in Europe. To obtain information about the epidemic
      situation of noroviruses in Switzerland, an initial study was launched in the
      German-speaking part of the country to systematically compile Norovirus outbreak
      information between 2001 and 2003. In total, 73 outbreaks were registered. Most
      affected were closed settings, e.g. nursing homes (34%) and hospitals (25%).
      Transmission pathways were identified in 74% of Norovirus outbreaks. In 81% of
      these cases person-to-person transmission was the primary route of infection and
      on seven occasions (13%), a foodborne transmission was the possible cause.
      Furthermore, Norovirus outbreak characteristics of epidemiological importance are
      highlighted with a discussion of four selected events.

PMID- 15962550
TI  - Temporally distinct Escherichia coli 0157 outbreaks associated with alfalfa
      sprouts linked to a common seed source--Colorado and Minnesota, 2003.
AB  - Escherichia coli O157 outbreaks were identified in Minnesota in February 2003
      involving seven persons and in Colorado in July 2003 involving 13 persons. Case
      isolates from the two states had matching pulsed-field gel electrophoresis (PFGE)
      patterns. Independent case-control studies linked infections in each outbreak
      with eating alfalfa sprouts that were traced to the same seed distributor. The
      Colorado sprouter reportedly complied with the Food and Drug Administration (FDA)
      sprout guidance, whereas the Minnesota sprouter did not. These investigations
      revealed that increased compliance with existing FDA guidance is needed and that
      additional research is needed to improve the alfalfa seed decontamination
      process. This reaffirms the FDA recommendation that raw alfalfa sprouts should be
      considered potentially contaminated and avoided by persons at high-risk such as
      the elderly, young children, and immunocompromised persons. PFGE played an
      essential role in linking these two temporally and geographically distinct E.
      coli O157 outbreaks.

PMID- 15962551
TI  - Modelling the epidemiology of Verocytotoxin-producing Escherichia coli serogroups
      in young calves.
AB  - We investigate the epidemiology of 12 Verocytotoxin-producing Escherichia coli
      (VTEC) serogroups observed in a calf cohort on a Scottish beef farm. Fitting
      mathematical models to the observed time-course of infections reveals that there
      is significant calf-to-calf transmission of VTEC. Our models suggest that 40% of
      all detected infections are from calf-to-calf transmission and 60% from other
      sources. Variation in the rates at which infected animals recover from infection
      by different VTEC serogroups appears to be important. Two thirds of the observed
      VTEC serogroups are lost from infected calves within 1 day of infection, while
      the rest persist for more than 3 days. Our study has demonstrated that VTEC are
      transmissible between calves and are typically lost from infected animals in less
      than 1 week. We suggest that future field studies may wish to adopt a tighter
      sampling frame in order to detect all circulating VTEC serogroups in similar
      animal populations.

PMID- 15962552
TI  - Transmission of F4+ E. coli in groups of early weaned piglets.
AB  - The aim of this study was to estimate transmission parameters of enterotoxigenic
      F4+ Escherichia coli F4 (F4+ E. coli) in groups of early weaned piglets with F4
      receptor-positive (F4R+) and F4-receptor-negative piglets (F4R-). Transmission of
      F4+ E. coli was quantified in four heterogeneous groups of F4R+ and F4R- piglets.
      Infectiousness was determined by the number of F4+ E. coli/g faeces shed during 8
      days. Transmission parameters were estimated using generalized linear models
      assuming a stochastic SIR model. F4R+ piglets were found to be more susceptible
      than F4R- piglets, but F4R+ and F4R- piglets were not different in
      infectiousness. The reproduction ratios for homogeneous F4R+ and F4R- populations
      were estimated as 6.37 (95% CI 1.89-21.48) and 0.02 (95% CI 0.00-1.13)
      respectively. The implication of these results is that in order to prevent major
      outbreaks, the fraction of F4R+ piglets should be small (approximately 10% or
      less). Therefore, selective breeding programmes could contribute to reducing F4+
      E. coli-related diarrhoea and transmission.

PMID- 15962553
TI  - Shigellosis remains an important problem in children less than 5 years of age in
      Thailand.
AB  - This is a review of existing data on the burden of shigellosis in Thailand to
      determine trends, vulnerable groups, predominant species and serotypes, and
      antimicrobial resistance patterns. Diarrhoea and dysentery morbidity and
      mortality data from 1991 to 1999 was collected from the routine surveillance
      system and demographic data from the government census. International and local
      literature published between 1988 and 2000 was systematically reviewed. Based on
      the routine surveillance system, the annual incidence of bacillary dysentery
      decreased from 1.3 to 0.2/10,000 persons per year. The remaining burden is
      highest in children <5 years of age at 2.7/10,000 persons per year. In
      comparison, a prospective study utilizing active surveillance found an incidence
      in children <5 years of age that was more than 100-fold higher at 640/10,000
      persons per year. Despite the decrease in morbidity and mortality based on
      routinely collected data, shigellosis remains an important problem in children <5
      years of age in Thailand.

PMID- 15962554
TI  - Risk factors for toxoplasmosis in pregnant women in Kent, United Kingdom.
AB  - The aim of this study was to establish the relative importance of various risk
      factors for toxoplasmosis in a United Kingdom antenatal population. Toxoplasma
      immune status was determined by an immunoassay and linked to a questionnaire
      exploring dietary and environmental exposure to toxoplasmosis. The overall
      seroprevalence found was 9.1% (172/1897). A significantly higher seroprevalence
      was associated with rural location of the childhood home, childhood home in
      Europe excluding the United Kingdom, feeding a dog raw meat and increased age. A
      non-significant higher prevalence of toxoplasmosis was observed in women who had
      lived with a cat or kitten as a child. In contrast to recent European studies
      only weak associations between diet and toxoplasmosis were found. Gardening
      activity was not associated with seropositivity but a non-significant lower
      seroprevalence was seen in gardeners who always wore gloves. This study confirms
      that toxoplasma prevalence in the United Kingdom has continued to decline since
      the 1960s. The increasing seroprevalence with age found in this study, highlights
      the continuing need to educate women of childbearing age about the risk factors
      for toxoplasmosis.

PMID- 15962555
TI  - Incidence of congenital toxoplasmosis estimated by neonatal screening: relevance
      of diagnostic confirmation in asymptomatic newborn infants.
AB  - Congenital toxoplasmosis is rarely identified by routine clinical examination.
      The aim of this study was to estimate the incidence of the disease in the region
      of Ribeirao Preto, south-eastern Brazil. A definitive diagnosis was made on the
      basis of the persistence of anti-Toxoplasma IgG antibodies beyond 1 year of age.
      Blood samples obtained from 15,162 neonates and adsorbed onto filter paper were
      tested for anti-Toxoplasma IgM antibodies. Fifteen samples gave positive results.
      A definitive diagnosis was confirmed in five of the 13 infants (38.5%) who
      completed follow-up. These five infants presented with serum IgM and/or IgA
      antibodies, and clinical abnormalities. Disease incidence was estimated to be
      3.3/10,000 (95% CI 1.0-7.7), indicating the need for preventive measures.
      Neonatal screening is feasible, but screening tests with a better performance are
      required; positive screening results must be carefully confirmed.

PMID- 15962556
TI  - Penicillin-resistant pneumococcal meningitis: high antibiotic exposure impedes
      new vaccine protection.
AB  - The frequency of meningitis due to penicillin-resistant Streptococcus pneumoniae
      (PRP) has increased in recent years, making treatment failure more likely. It is
      currently expected that pneumococcal conjugate vaccines might curb this trend. We
      investigated this issue using a mathematical model applied to the current
      prevalence of resistance and antibiotic exposure in the United States and in
      France. Our main finding was that the level of antibiotic exposure may limit the
      effect of the vaccine. In relatively low antibiotic exposure environments such as
      the United States, large-scale vaccination prevents a large part of PRP
      meningitis cases, whereas in high antibiotic-exposure environments such as
      France, vaccination alone does not lead to a substantial reduction in PRP
      meningitis incidence. Our results suggest that antibiotic exposure reduction will
      remain of primary importance for the control of PRP meningitis despite wide scale
      use of pneumococcal conjugate vaccines.

PMID- 15962557
TI  - Serological and virological features of dengue fever and dengue haemorrhagic
      fever in Thailand from 1999 to 2002.
AB  - Serological and virological features of dengue fever (DF) and dengue haemorrhagic
      fever (DHF) in Thailand were analysed in 2715 patients from 1999 to 2002. The
      illness was caused by DEN-1 in 45%, DEN-2 in 32%, DEN-3 in 18% and DEN-4 in 5% of
      patients. Almost all of the DHF cases caused by DEN-2 and DEN-4 were in secondary
      infection, while approximately 20% of the DHF cases caused by DEN-1 and DEN-3
      were in primary infection. Male:female ratio and age distribution were not
      different among four serotypes in primary and secondary infections. These results
      indicate that DEN-1 and DEN-3 induce DHF in both primary and secondary
      infections, and suggest that DEN-2 and DEN-4 in Thailand are less likely to cause
      DHF in primary infections.

PMID- 15962558
TI  - Exposure time to hepatitis B virus and associated risk factors among children in
      Edirne, Turkey.
AB  - Hepatitis B virus (HBV) infection is endemic in Turkey, but the main routes of
      transmission were not well established. This study aims to detect the exposure
      time to HBV and associated risk factors among children. In a sampling group of
      children aged 0-19 years living in Edirne, antiHBc, antiHBs and HBsAg were
      screened by the microELISA method. A questionnaire was also completed for each
      child. In 717 children that were included in the study, the total antiHBc
      seropositivity was 5.4% and was 1.8, 0.8, 1.7, 6.8, 11.8% in 0-1, 2-5, 6-10, 11
      14, 15-19 years age groups respectively. The overall HBsAg seropositivity was
      1.7%. The risk of HBV infection increased after the age of 10 years (OR 7.79, 95%
      CI 3.01-20.16). Collective circumcision was the only independent factor according
      to regression analysis. Children living in Edirne should be vaccinated against
      HBV before reaching 11 years of age.

PMID- 15962559
TI  - Experimental rabies infection in haematophagous bats Desmodus rotundus.
AB  - In order to determine the susceptibility and serum neutralizing antibody response
      of Desmodus rotundus to rabies virus, bats were inoculated with a virus isolated
      from a naturally infected haematophagous bat. Bats were divided into four groups
      of 10 animals each. Dilutions of rabies virus containing 100, 1000, 10,000 and
      100,000 MICLD50 (lethal dose 50% for mice inoculated by the intracerebral route)
      were administrated in the pectoral muscle. The presence of rabies virus was
      detected in brain and salivary glands by fluorescent antibody, mouse inoculation
      and RT-PCR. The observed mortality for each virus dose was 0, 20, 20 and 60%
      respectively. Serum neutralizing antibodies were tested for by the rapid
      fluorescent focus inhibition test, and antibody titres greater than 0.5 IU/ml
      were found in 53% of bats 30 days after virus inoculation. Resistance to
      infection was seen in bats that developed low or no detectable antibody response
      as well as in bats with high titres. Among the 10 bats that died of rabies, eight
      showed signs of paralytic rabies and two bats showed no clinical signs.

PMID- 15962560
TI  - Molecular epidemiology of rabies in northern Colombia 1994-2003. Evidence for
      human and fox rabies associated with dogs.
AB  - During the period 2000-2003, wild grey foxes (Urocyon cinereoargenteus) in
      northern Colombia became infected with rabies. In order to derive phylogenetic
      relationships between rabies viruses isolated in foxes, dogs and humans in this
      region, 902 nt cDNA fragments containing the G-L intergenic region and encoding
      the cytoplasmic domain of protein G and a fragment of protein L were obtained by
      RT-PCR, sequenced and compared. Phylogenetic analysis showed that rabies viruses
      isolated in foxes, dogs and humans belonged to a single genetic variant.
      Speculative analysis together with epidemiological data indicated that rabies in
      foxes may have been due to contact with rabid dogs. Rabies transmission between
      dogs, wild foxes and humans may happen in natural conditions in northern
      Colombia. This finding is the first to suggest dog-to-fox rabies transmission in
      South America, and provides another example of dog rabies variants being able to
      successfully colonize wildlife hosts.

PMID- 15962561
TI  - Patterns of spread and persistence of foot-and-mouth disease types A, O and Asia
      1 in Turkey: a meta-population approach.
AB  - Despite significant control efforts, foot-and-mouth disease (FMD) persists in
      Turkey, and new strains of serotypes A, O and Asia-1 are periodically reported to
      enter the country from the east. The status of FMD in Turkey is important
      regionally because the country forms a natural bridge between Asia where the
      disease is endemic, and Europe which has disease-free status. This study analysed
      spatial and temporal patterns of FMD occurrence in Turkey to explore factors
      associated with the disease's persistence and spread. Annual records of FMD
      distribution in Turkish provinces throughout 1990-2002, grouped by serotype (O, A
      and Asia 1), were analysed using geostatistical techniques to explore their
      spatial and temporal patterns. A meta-population model was used to test how
      disease status, expressed in terms of presence/absence, extinction, and
      colonization, and measured at the province level throughout the periods 1990-1996
      and 1997 2002, could be predicted using province-level data on: ruminant
      livestock numbers; meat production-demand discrepancy (as a surrogate measure of
      animal and animal products marketing, i.e. long-distance contagion through the
      traffic of mainly live animals to urban centres); and the disease prevalence
      distribution as recorded for the previous year. A drastic overall reduction in
      FMD occurrence was observed from the period 1990-1996 to 1997-2002 when the
      disease was shown to retract into persistence islands. FMD occurrence was
      associated with host abundance, short distance contagion from adjacent provinces,
      and meat production-demand discrepancies. With FMD retracting into identified
      provinces, a shift in predictors of FMD occurrence was observed with a lower
      contribution of short-distance contagion, and a relatively higher association
      with meat production-demand discrepancies leading to live animal transport over
      long distances, and hence presenting opportunities for identifying critical
      control points. The pattern of persistence differed according to serotype groups
      and is discussed in relation to their differential affinity to cattle and small
      ruminant hosts.

PMID- 15962562
TI  - The occurrence of encephalomyocarditis virus (EMCV) in European pigs from 1990 to
      2001.
AB  - The occurrence of encephalomyocarditis virus (EMCV) among domestic pigs and wild
      boar in several European countries is described and discussed. From 1990 to 2001
      clinical outbreaks were analysed and serum samples, partly from existing
      screening programmes, were tested for antibodies against EMCV. Most clinical EMCV
      outbreaks were reported in Belgium (320), followed by Italy (110), Greece (15)
      and Cyprus (6). The outbreaks appeared to be clustered in 'endemic areas' with an
      increase in outbreaks during the autumn and winter months. The within-herd
      seroprevalence measured in clinically affected pig farms varied considerably
      among farms (2-87%), with age (0-84%) and by country. Data from farms with no
      clinical disease showed that subclinical infection with EMCV was found both
      within (seroprevalence 6-62%) and outside (up to 17 %) the endemic areas of the
      clinically affected countries as well as in the non-clinically affected countries
      Austria and France (3-5.4%). Among wild boar, the seroprevalence varied between
      0.6 and 10.8%, and a study in Belgium found a prevalence of virus infection of
      3.3%.

PMID- 15962563
TI  - Incidence and persistence of classical swine fever in free-ranging wild boar (Sus
      scrofa).
AB  - Although veterinary authorities aim to limit persistence of classical swine fever
      (CSF) in wild boar (Sus scrofa), to avoid potential transmission to pigs, factors
      influencing CSF transmission and persistence are not clearly understood. Here we
      analyse incidence and persistence in a CSF epidemic that occurred in the French
      Vosges Forest. Higher incidence was found in large forests compared to smaller
      isolated ones, being highest near the starting point of the epidemic, but poorly
      related to the local density. We hypothesize that the spatial and social
      structure of wild boar populations may be responsible for this variability of
      incidence over space. Persistence was highest near the starting point of the
      epidemic and where initial density was highest. We hypothesize that persistence
      was favoured by the abundance of young wild boar, itself encouraged by CSF. Our
      results allow us to propose management measures aimed at limiting CSF
      persistence.

PMID- 15962564
TI  - Helicobacter pylori seropositive subjects do not show a pronounced systemic
      inflammatory response even in the presence of the interleukin-1 receptor
      antagonist gene polymorphism.
AB  - The aim of this analysis was to evaluate the effects of the presence of the IL
      1RA gene polymorphism and H. pylori infection on markers of a systemic
      inflammatory response taking into account virulence markers of this infection.
      Serum concentrations of interleukin (IL)-6, IL-8, and tumour-necrosis factor
      (TNF)-alpha of 479 occasional blood donors were not statistically significantly
      higher in subjects having antibodies against H. pylori, or more specifically
      against CagA and VacA, and being homozygous for the pro-inflammatory IL-1RN*2
      allele compared to others after adjustment for covariates. The findings suggest
      that the possible pro-inflammatory effect of the IL-1RN*2 allele in combination
      with H. pylori infection is limited to the mucosal level.

PMID- 15962565
TI  - The incidence and expression of the subcondylar tubercle of the mandible in early
      Polynesians, modern Indians and modern Europeans.
AB  - A sample of pre-European Polynesian and Melanesian mandibles, modern Asian
      Indians and cadaveric European mandibles were investigated to establish the
      prevalence of a subcondylar tubercle and to attempt to relate its presence to
      mandibular function. Among the three population samples, the subcondylar tubercle
      appeared 1.5 times more frequently among the Polynesians/Melanesians, than either
      the Indian or European groups. It was fairly equally present on both sides in all
      three groups. Where it was present unilaterally, it was far more likely to be
      present on the left side. This left-side presence coincided with a significantly
      greater right-side condylar height and ramal width.

PMID- 15962566
TI  - Haemogenetic studies in Bulgaria.
AB  - Within a study of the genetics of Bulgarian populations, the markers AB0, RH,
      MNS, P, HPA, GM(1), PGM1, ACP and ESD were examined in 2346 individuals from
      seven subpopulations of south-central and south-eastern Bulgaria. The combined
      data have been compared with other populations of the Balkans.

PMID- 15962567
TI  - Reproductive pattern in agrarian and immigrant receptor populations: a survey of
      El Ejido (SE Spain).
AB  - This paper deals with the fertility pattern of the El Ejido population, an
      agricultural Spanish community characterised by the rapid development of its
      modern agrarian economy. Consequently, the arrival of immigrants has sharply
      increased throughout the second half of the twentieth century, with important
      demographic consequences as well as reproductive changes. The analyses of the age
      specific fertility rate (fx) and the total fertility rate (TFR) were used in
      order to describe the reproductive pattern of this population in 2000. The main
      characteristics were the following: a) Regarding the temporal change, an
      important decrease of fx has been observed in all age groups for the last twenty
      years, as a consequence of progressive birth control. However, the reproductive
      pattern has kept almost invariable and has been characterised by a maximum
      fertility at age group of 25-29 years old. b) Regarding the general Spanish
      fertility, the comparison of fx in both populations suggests a younger maternity
      in the agricultural population than in the national, the maximum fertility
      delayed to the 30-34 age group. c) Moreover, the El Ejido population showed a
      clear higher offspring per woman (TFR = 1.42) than the national (TFR = 1.24),
      according to the agrarian character of the El Ejido population. d) Finally, this
      greater reproductive level of El Ejido is also due to the arrival of women at
      fertile age, who come mainly from Africa, and above all from Morocco.

PMID- 15962568
TI  - Genetic analysis of bilateral dermatoglyphic asymmetry in twins and their
      parents.
AB  - The data for this study were collected on 64 twin pairs (30 MZ and 34 DZ) and
      their 128 parents. Two following hypotheses were evaluated: 1. Bilateral
      asymmetry is significantly genetically controlled; 2. The twinning phenomenon
      would affect the magnitude of bilateral asymmetry. The results revealed no
      statistically significant differences between mean values of MZ and DZ twins and
      their parents for the majority of the traits. Significant differences were
      recorded for only 6 of 96 comparisons (6%). Analysis of variance revealed
      separated sources of MZ, DZ and singleton variance. F-ratios, contrasting
      variances between different groups were significant for 26 of 96 comparisons
      (27%) showing heterogeneity of variance between zygosities and between twins and
      their parents. In addition, environmental covariance appeared to be larger for MZ
      than DZ with respect to directional asymmetry (DA) for all 16 traits and
      fluctuating asymmetry (FA) for 14 traits. These observations showed complex
      environmental determinism for bilateral asymmetry for the majority of
      dermatoglyphic traits. Significant genetic variance ratios (GVRs) were observed
      for four variables (25%) with respect to DA and three variables (18.75%) with
      respect to FA. All these significant GVRs were rendered insignificant because of
      evidence of greater environmental covariance for MZ twins, except possibly for DA
      for URC4.

PMID- 15962569
TI  - [The eruption times of permanent teeth in boys and girls in the Stormarn
      District, Schleswig-Holstein (Germany)].
AB  - In a longitudinal study in two small towns in southern Schleswig-Holstein
      (Ammersbek and Ahrensburg, District Stormarn; 9155 inhabitants) we investigated
      2832 oral findings of 1396 patients (711 males, 685 females). The minimum age was
      1.51 years, and the maximum age was 25.50 years. The dental findings were
      collected over a period of about 20 years (1982-2002). The oral findings per
      child were assessed between one and eight times. The eruption times of teeth in
      females are earlier than those for the same teeth in males. Further, the
      permanent dentition in females is completed earlier than in males. In both sexes
      the tooth eruption occurs symmetrically in both jaws. The comparison of both jaws
      revealed a slightly advanced eruption of the lower jaw teeth in both sexes. There
      is a noteworthy change in the eruption sequence of the teeth. In contrast to
      other reports we observed that the eruption of the canine proceeds the eruption
      of the second molar. We found no acceleration of the dentition when compared with
      other reports and could confirm the rules of tooth eruption in man. CONCLUSION:
      Oral examination of teeth is a simple tool to calculate tooth eruption intervals.
      This first investigation on a population of Schleswig-Holstein revealed a change
      in the eruption sequence of permanent teeth. These findings are relevant for
      dental treatment planning and should be reconfirmed at certain intervals.

PMID- 15962570
TI  - A multivariate study of three body measurements of different states of India.
AB  - Considerable attempts have been made to study the changes in three important body
      measurements (viz. body height, body weight and chest circumference) in young
      healthy males between different states of India using univariate statistical
      analysis in which body measurements are assumed to be independent of each other.
      Actually these body measurements are correlated with each other and thus the
      assumption of independence is violated in univariate statistical analysis. Hence
      the results obtained by univariate statistical analysis may be misleading. An
      attempt has, therefore, been made in the present study to apply multivariate
      statistical analysis in order to have an idea about the simultaneous changes in
      these three correlated measurements between different states of India in healthy
      Indian males of age ranging from 16-21 years. It has been concluded that
      significant changes take place in these three body measurements simultaneously of
      young healthy males of 16-21 years of age between different states of India.

PMID- 15962571
TI  - The relationship of age, body mass index and waist circumference with blood
      pressure in Bengalee Hindu male jute mill workers of Belur, West Bengal, India.
AB  - A cross-sectional study of 150 adult Bengalee Hindu male jute mill workers of
      Belur, a suburb of Kolkata, West Bengal, India, was undertaken to study the
      relationship of age, body mass index (BMI) and waist circumference (WC) with
      systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure. The mean
      age and the BMI of the subjects were 40.7 years (S.D. = 15.2) and 23.2 kg/m2
      (S.D. = 3.2), respectively. The mean SBP, DBP and MAP were 124.7 mmHg (S.D. =
      7.8), 81.5 mmHg (S.D. = 5.7) and 95.9 mmHg (S.D. = 6.1), respectively. Age had
      similar significant (p < 0.001) correlations with BMI and WC. Age and WC were
      significantly correlated (p < 0.001) with all the three blood pressure variables.
      In general, the correlations of BMI with SBP (r = 0.24, p < 0.01), DBP (r = 0.15,
      n.s.) and MAP (r = 0.19, p < 0.05) were weaker. Age controlled multiple
      regression analyses demonstrated that BMI did not have a significant effect of
      any blood pressure variable. However, WC had a significant impact (p < 0.0001) on
      SBP (t = 7.068), DBP (t = 5.190) and MAP (t = 6.387), even after adjusting for
      the effect of age. Moreover, even after age adjustment, percent variations in SBP
      (20.7%), DBP (12.5%) and MAP (17.2%) explained by WC were high. This significant
      impact (p < 0.0001) of WC on SBP (t = 9.426), DBP (t = 8.349) and MAP (t = 9.642)
      remained even after controlling for the combined effects of age and BMI.

PMID- 15962572
TI  - The influence of anthropometrical and flexibility parameters on the results of
      breaststroke swimming.
AB  - The aim of this investigation was to study the possible relationships between
      anthropometry, flexibility and specific swimming results in female breaststroke
      swimmers. Subjects were 125 female breaststroke swimmers in age of 11-18 years.
      Body height and mass were measured and BMI (kg/m2 ) and Broca index (body height
      in cm - 100 = weight in kg) were calculated. The flexibility of hip external
      rotation, knee external rotation, ankle dorsal flexion and ankle supination were
      measured with plastic goniometer. 100 m breaststroke swimming using kickboard and
      legs only was used as a swimming performance parameter. The number of kicks was
      also fixed. Horizontal jumping ability was measured using a simple standing broad
      jump (cm) minus body height (cm). As a rule, flexibility in different joints did
      not depend on anthropometrical parameters. Only knee external rotation and ankle
      dorsal flexion correlated significantly with body mass (r = -0.221 and r = 
      0.210, respectively) and BMI (r = 0.242 and r = 0.204, respectively). The
      relationship between flexibility in different joints, as a rule, was not
      significant. Stepwise multiple regression analysis indicated that from the used
      anthropometrical parameters the most important was the body height, which
      explained 11.1% (R2 x 100) of the 100 m breaststroke swim results using legs
      only. The most important parameter from the measured flexibility indices was knee
      external rotation (11.1%, R2 x 100). Combination of knee external rotation and
      ankle supination increased the determination coefficient to 24.4%. Finally, three
      flexibility measures (knee external rotation, ankle supination, hip external
      rotation) explained the swimming results by 28.2% (R2 x 100). It was concluded
      that the good flexibility is more important than single anthropometrical
      parameters when explaining the breaststroke swimming results using kickboard and
      legs only.

PMID- 15962573
TI  - [ Recommendations for the forensic and age determination from the skeleton].

PMID- 15962574
TI  - Introduction: quality improvement in public sector healthcare organizations.

PMID- 15962575
TI  - Quality improvement in a federally funded community breast and cervical cancer
      screening program.
AB  - Continuous Quality Improvement (CQI) methods offer healthcare organizations
      valuable tools for improving services to their patients. These tools are also
      useful in improving the way an organization delivers its services. In this case
      study, the authors describe the use of quality improvement activities for
      improving the enrollment and screening for breast and cervical cancer for the
      Women's Health Connection (WHC). The WHC is operated by the Nevada Department of
      Human Resources, Health Division, to provide screening for income eligible women
      between the ages of 40-64. Funding for the WHC was provided by the Department of
      Health and Human Services' Centers for Disease Control and Prevention (CDC)
      through the National Breast and Cervical Cancer Early Detection Program
      (NBCCEDP). By using Quality Improvement Teams, the WHC was able to restructure
      the way women were being enrolled in the program in order to increase the number
      of women screened and to help the program meet CDC performance indicators. This
      article documents the quality improvement process used in the case study,
      highlights the areas improved, and demonstrates how quality improvement was
      useful in improving services provided to women. It also describes staff
      acceptance of the quality improvement process and its potential future
      applications.

PMID- 15962576
TI  - End-user perceptions of a computerized medication system: is there resistance to
      change?
AB  - Public mandate to control cost, while improving quality of service, leads health
      care administrators to look to information technology for innovative solutions.
      This case study of acute care registered nurses in a public hospital focuses on
      experiences of the end-users of a computerized medication system. Data was
      obtained by in-depth interviews and observation performed in the clinical
      setting. Findings fell into five challenging issues to the end-user and health
      care administration: end-user perceptions of inadequate training, negative
      experiences of implementation, perceived deficiencies in quality of technology,
      perceptions of lack of participatory design and a ensuing circumvention of the
      new system. Emphasis is on the relationship of the findings to the quality of
      public health care administration.

PMID- 15962577
TI  - Re-engineering the Los Angeles County public health care safety net:
      recommendations from a Blue Ribbon Health Task Force.
AB  - Public hospitals throughout the United States are under increasing fiscal and
      political pressure to survive because of dynamic changes in healthcare delivery,
      an increasing uninsured population of patients and rapidly declining
      reimbursement. These safety net health care programs are also saddled with
      outdated and bureaucratic governmental policies and procedures which make it even
      more difficult to improve the quality of care and efficiency of the organization.
      As these pressures mount, some public hospital systems have attempted to be
      reinvented through the re-engineering process. Los Angeles County, the second
      largest health system in the United States, has done relatively little to adjust
      to changing times. Los Angeles County Department of Health Services has been
      attempting to re-engineer for the past three years, but this has not averted the
      need for a second billion-dollar waiver in 2000 from the state and federal
      governments. A Blue Ribbon Health Task Force was appointed to examine the failure
      of re-engineering to restructure the Los Angeles public health delivery system.
      In this article, the group's findings and recommendations are reported. They
      cover three general areas: eliminating bureaucratic hurdles, improving healthcare
      planning and management of operations and setting priorities on critical
      investments in health services.

PMID- 15962578
TI  - A cohort study of former and current Medicaid recipients in two North Carolina
      counties, 1996-1999.
AB  - This article presents findings of a 1998-99 resurvey of Medicaid recipients
      (adults and children) who were first surveyed in 1996 in Mecklenburg and New
      Hanover Counties in North Carolina. It reports the insurance status and health
      care of former Medicaid recipients and compares them with those still on Medicaid
      in 1998-99 in respect to access to care and satisfaction. Just under half of
      those who had left Medicaid were without employer-sponsored health insurance
      (ESI) at the time of the second survey. Former Medicaid recipients without ESI
      rated their access to healthcare lower than those with Medicaid and former
      Medicaid recipients with ESI. Over 50% of target respondents in all groups were
      more positive than negative on access-related variables. But only those on
      Medicaid in Mecklenburg County had significant increases in satisfaction with
      health care between 1996 and 1998-99. Those in the control county who were off
      Medicaid and those still receiving it and former recipients in Mecklenburg showed
      no significant change. The study has great policy relevance in light of recent
      national welfare reform.

PMID- 15962579
TI  - [Opportunistic pathogens and infections].

PMID- 15962580
TI  - [Basic evaluation of BACTEC MGIT 960 Series for drug susceptibility testing of
      antimicrobial agents against Mycobacterium tuberculosis].
AB  - This time, we compared conventional method Well pack P (the proportion method on
      Ogawa egg medium) with automated instrument BACTEC MGIT 960 AST system for
      Mycobacterium tuberculosis drug susceptibility testing. Fifty-three M.
      tuberculosis stock strains were used. Concordance rates between the two methods
      were SM: 94.3%; INH: 100%; RFP: 100%; and EB: 90.5%. All 23 drug-susceptible
      strains corresponded to four drugs. Discrepant results were observed in six of 30
      drug-resistant strain. The mean times for results from the MGIT 960 AST system
      was 8.7 days. On the other hand, with Well pack P, growth of drug resistant
      strains was slow, and it was still difficult to judge four weeks later. Although
      the MGIT 960 AST system has problems, such as its high cost of labor and
      reagents, and the confirmation of contamination, because it is an automatic
      instrument, there are no discrepancies due to different technician techniques.
      The MGIT 960 AST system was found to be a rapid and excellent method.

PMID- 15962581
TI  - [Evaluation of beta-lactamase detection reagent with used HMRZ-86 for the
      detection of extended-spectrum beta-lactamase and metallo-beta-lactamase].
AB  - Currently, evidence related to infectious diseases and the nosocomial infection
      in hospitals with Gram-negative rods with extended spectrum beta-lactamase (ESBL)
      or metallo-beta-lactamase (MBL) is accumulating. Thereby, it will be very
      important to know quickly the resistant mechanisms for antibiotics in the
      treatment strategy of patients with infectious diseases in a clinical setting.
      Then, beta-lactamase detection reagent Cica beta-Test (Kanto Chemical, Tokyo)
      which used HMRZ-86 was evaluated. Bacteria used in the present study were 42
      stocked strains of beta-lactamase produced strain isolated from clinical samples
      in our hospital. ESBL were coincided in 13 strains among 17 (76.5%). MBL were
      coincided in 8 strains among 11 (72.7%). KOXY belongs to class A beta-lactamase
      was missjudged as ESBL. Therefore, although there are a little of limitations.
      Cica beta-Test provides us the rapid information of the esistance mechanism in 15
      min with relatively, which is surely valuable to treat patients with bacterial
      infection and to prevent the nosocomial infection.

PMID- 15962582
TI  - [The role of the "infection control nurse (ICN)" in an outbreak].
AB  - The nosocomial infection and its expansion is a big problem for both customers
      and healthcare organizations. It is one of the most important tasks for the
      infection control team to prevent spreadng the hospital infection and to minimize
      its damage for clients and healthcare organizations. Japanese nurse association
      (JNA) has established the system of the certified nurses who finished authorized
      certification program in 15 areas including infection control in 1999. They are
      called "Certified Expert nurse (CEN)" and the number of CEN concerning about
      infection control (ICN) has reached 146 nurses in Japan in 2004. ICNs should have
      an ability to predict the possibility of an outbreak and to take measures to meet
      the situation, practically direct intervention and research for the outbreak. In
      this literature I have summarized the roles of ICN, introducing our experience of
      the scabies outbreak in our affiliated intermediate care facility for the senior
      citizens. It is important for ICN to research and analyze the outbreak, at the
      same time we have to feedback effectively to the healthcare stuffs to change
      their attitude and develop the system to discover the outbreak earlier by
      educating them.

PMID- 15962583
TI  - [The effects of associative strength between lexical and conceptual
      representations on word processing in second language learners].
AB  - The purpose of this study was to examine how the learning experience affects
      associative strength between lexical representations of first and second language
      (L1, and L2) and conceptual representation, and word processing. The critical
      experimental manipulations were L2 proficiency, word frequency, and matching
      direction. The subjects were advanced learners and beginners. Association
      strength was assessed by measuring reaction time and error rate in translation
      recognition tasks with three sets of English (L2) and Japanese (L1) words that
      were high or low frequency, and corresponding pictures. The results showed that
      (1)the two associations involving L2 words were stronger when L2 word frequency
      was high, (2)both L2-L1 and L2-Picture association were strengthened with L2
      proficiency. However, (3)there was no difference between L2-L1 and L2-Picture
      conditions. Moreover, (4) the association between L1 words and pictures were
      strong regardless of L2 proficiency or word frequency. These results suggest that
      L2 learning experience strengthens both associations involving L2 words.

PMID- 15962584
TI  - [The effects of bereavement of friends on depression in adulthood: age and family
      support as moderators].
AB  - The purpose of this longitudinal study was to examine the moderating effects of
      age and social support from family members in the relationship between the
      bereavement of friends and depression. The participants were 1 402 Japanese
      community-dwelling men and women aged between 40 and 79 years, who had done the
      baseline and the two-year follow-up surveys of the National Institute for
      Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). By using hierarchical
      multiple regression analysis, we detected a significant interaction between age,
      social support from family members, and the bereavement of friends. Younger
      participants who were receiving less support from family members after the loss
      of friends showed significantly higher depression scores.

PMID- 15962585
TI  - [Social support and acceptance of the disease by parents of children who have
      progressive muscular dystrophy].
AB  - The purpose of this study was to investigate the relationship in the parents
      among social support, psychological stress response, and acceptance of the fact
      that their children had progressive muscular dystrophy. Parents of progressive
      muscular dystrophy patients, 326 in total, completed a questionnaire that
      included scales of social support, acceptance of muscular dystrophy, positive
      thought on child's muscular dystrophy, and psychological stress response. Results
      of analysis of variance (ANOVA) indicated that features of the social support
      received by the parents differed at different stages of the disease, but levels
      of acceptance of the disease and psychological stress response were not
      different. Results of analysis of covariance structure suggested that social
      support increased parent's positive cognition about the disease, the cognition in
      turn increased their acceptance of the disease, and the acceptance reduced
      psychological stress responses. Finally, social support systems that were
      available to the parents of children with muscular dystrophy were discussed.

PMID- 15962586
TI  - [Appraisal dimensions of emotions: an empirical integration of the previous
      findings].
AB  - Appraisal theories of emotions assume that the emotions are elicited by the
      appraisals of events or circumstances along with the several dimensions. However,
      there are some inconsistencies among the dimensions proposed by various appraisal
      theories. The purpose of this study was to integrate the appraisal dimensions
      that were proposed by Scherer, Roseman, and Smith & Ellsworth's theories by
      empirically investigating the appraisals associated with each emotion. Three
      hundred seventy-six Japanese participants recalled a past experience associated
      with one of 13 emotions, and rated the nature of the emotional event along the
      appraisal dimensions proposed by them. A factor analysis identified eight
      factors: pleasantness, self/other control, certainty, anticipated effort and
      attention, novelty, human/situation control, motivational state, and coping
      potentials. These dimensions were consistently proposed by the appraisal
      theorists. Moreover the associations between each emotion and its appraisal
      profiles were mostly consistent with the previous theories except for a few
      dimensions. Discussion argued that the appraisal dimensions identified in this
      study adequately capture the important features of major emotions.

PMID- 15962587
TI  - [The effects of information of the other's cooperative behavior on moral
      obligation].
AB  - Although it is expected that a social dilemma is solved by giving people feedback
      information about others' cooperative behavior, previous studies demonstrated
      that the information may promote cooperative behavior in some situations but may
      promote non-cooperative behavior in other situations. The study hypothesize that
      the feedback information of the others' cooperative behavior promote cooperative
      behavior for those who feel high obligation to cooperate in a social dilemma
      situation, such as a problem of bicycle parking behavior on road, but promote
      defective behavior for those who have low moral obligation. This is because the
      former people are hypothesized to attribute the cause of other's cooperative
      behavior to their social and intrinsic motivation, but the latter are
      hypothesized to attribute it to the egoistic motivation. The data from an
      experiment (n = 126) supported the hypotheses.

PMID- 15962588
TI  - [A study of attentional resource of discrete and gradational allocation strategy
      using error-related negativity (ERN)].
AB  - The error-related negativity (ERN) is a component of the event-related brain
      potential (ERP) that is associated with action monitoring and error detection.
      The ERN amplitude reflects attentional resource allocated to error detection. The
      present study examined whether discrete or gradational allocation strategy of
      attentional resource in error detection using the ERN amplitude. Only Eriksen
      flanker task was used in the single task condition. Eriksen flanker task was used
      as a primary task and Sternberg memory search task was used as a secondary task
      in the dual task conditions. The task difficulty of the secondary task
      manipulated in the present study included the memory load. Memory set sizes of 2,
      4 and 6 were used in the Sternberg memory search task (M2, M4 and M6 conditions).
      The results indicated that reaction time was gradually delayed in the primary
      task as the task difficulty of the secondary task gradually increased. However
      the ERN amplitude of the primary task decreased in M6 condition alone. In
      conclusion, discrete allocation strategy of attentional resource was adopted in
      the error detection.

PMID- 15962589
TI  - [The effect of location of a highlight in a shaded circle on depth perception].
AB  - Two experiments were performed to examine how the apparent depth of a shaded
      circle on a plane was affected by the direction and the distance of a highlight
      in the shaded area from the center of the circle. Fourteen undergraduates were
      asked to rate the concentrically shaded circle according to the apparent depth
      using the method of magnitude estimation. Experiment I showed that the rating was
      the highest in the upper-left, upper-right, and top conditions of the direction
      and the lowest in the bottom condition. Experiment 2 showed that the rating was
      the highest when the highlight was located at a third of the diameter of the
      circle apart from the center and the lowest when the highlight was on the edge of
      the circle or in the center. On the whole, the results support Ramachandran's
      "Assumption of Light From Above", which states that humans perceive a circle
      shaded bright in the top and dark in the bottom as convex due to their long
      experience on the earth since their birth.

PMID- 15962590
TI  - [Rewarding property of nicotine and methamphetamine tested by conditioned place
      preference in rats: effect of chronic nicotine pretreatment].
AB  - Nicotine is classified as a dependence-producing drug. This study investigated
      the rewarding property of nicotine employing the conditioned place preference
      (CPP) paradigm in a three-compartment box, and compared it with that of
      methamphetamine (MAP). In place conditioning using a biased method, rats were
      placed in one (white or black) compartment under the drug treatment and placed in
      the other compartment without drug. In the preference test conducted after
      conditioning, the time spent in the nicotine-paired compartment significantly
      increased compared with that in the baseline test, suggesting nicotine's
      rewarding property, although the property was weaker compared with that of MAP.
      Chronic nicotine pretreatment by a subcutaneous osmotic mini-pump for 7days
      before place conditioning tended to increase the rewarding property of nicotine,
      and the possible mechanism of this effect was discussed.

PMID- 15962591
TI  - [Reconsideration of the role of shape similarity in preschooler's inference about
      word meanings].
AB  - This study examined how children used shape similarity information when they
      inferred the meaning of a novel label which was given to a familiar object. When
      children were shown two objects similar only in shape (white paper cup and
      glass), 5 : 7- to 6 : 7-year-old children (N = 28, M = 5 : 11) assigned the novel
      label only to the object identical to the target, whereas 4 : 7- to 5 : 6-year
      old children (N = 28, M 4 : 11) mapped the novel label to all objects within the
      familiar object category. When children of both age groups (N = 15, M = 5 : 8,
      range = 5: 3 to 6 : 2; N 12, M = 4 : 10, range = 4 : 3 to 5 : 1) were shown two
      paper cups identical except color (white paper cup and pink one), children
      selected both of the two objects. These results showed children in both age
      groups regarded the objects identical except color as those given the same label;
      on the other hand, children did not think of the objects similar only in shape as
      qualified for the same label. Therefore the results imply that what is treated as
      "shape similarity" in this area of research includes the similarity not only in
      shape but also in other dimensions such as material.

PMID- 15962592
TI  - [Improvement of psychic health preservation system in servicemen].

PMID- 15962593
TI  - [Methodological aspects of evaluation of servicemen life quality].

PMID- 15962594
TI  - [Medical-and-social risk factors of pneumonia and acute bronchitis occurred in
      recruits].

PMID- 15962595
TI  - [The experience of videoendoscopic subfascial dissection of perforated veins].

PMID- 15962596
TI  - [The orthopedic stage of complex treatment of the wounded with mandible defects].

PMID- 15962597
TI  - [The efficiency of modern methods of narcomania prevention used in RF MD
      educational centers].

PMID- 15962598
TI  - [Sonapax use in the clinical practice].

PMID- 15962599
TI  - [Reflexotherapy used in excretory-and-inflammatory form of male infertility].

PMID- 15962600
TI  - [Theoretical premises to development of air force medicine].

PMID- 15962601
TI  - [Technical means of the new generation used for autonomous supply of the mobile
      medical formations of RF Armed Forces medical service with oxygen].
AB  - According to the tasks and initiative of RF MD Main Military Medical Headquarters
      the series of research and experimental designers' work was performed. It allowed
      determining the main principles of anew conception of supplying the mobile
      medical formations with oxygen and creating the necessary technical means for its
      realization, i.e. for autonomous supply of medical service troop link with
      oxygen. The most optimal schemes of new technical mean application to obtain the
      oxygen at the stages of medical evacuation were worked out. The oxygen supply
      system based on the use of created technical means of its production is easily
      adapted to dynamically changing problems of medical service. The state trials
      have confirmed the prospects of the conception proposed.

PMID- 15962602
TI  - [Record optimization and control of medical property stocks].
AB  - To conduct the adequate control of medical property coming to the medical
      provision institution the software was developed where the special attention was
      paid to the functions of control-and-operational department. It is conditioned by
      the fact that together with cost control it is necessary to record the medical
      property in natural values. The use of the created program in local net system
      allowed organizing the operative control of material stocks at all stages of its
      movement.

PMID- 15962603
TI  - [The use of infusion solutions manufactured in the field conditions].

PMID- 15962604
TI  - [The main Military Sanitary Headquaters of the Red Army during the period of
      Great Patriotic War].

PMID- 15962605
TI  - [Does the treatment delay influence reperfusion efficacy and short- and long-term
      left ventricular function in patients with anterior myocardial infarction treated
      with primary coronary angioplasty?].
AB  - The benefit of thrombolysis in acute myocardial infarction (AMI) is time
      dependent, but there is lack of evidence of such a close correlation in patients
      undergoing primary percutaneous transluminal coronary angioplasty (pPTCA). The
      aim of this study was to evaluate the importance of delay of treatment for
      myocardial reperfusion and early and late ventricular function in patients with
      anterior AMI treated with pPTCA. METHODS: 106 consecutive patients (76 men, 30
      women, age 63 +/- 11 years) treated with pPTCA for anterior AMI was included in
      this study. We evaluated angiographic (myocardial blush grade (MBG), TIMI flow,
      corrected TIMI frame count) and electrocardiographic (resolution of ST segment
      elevation--nST) markers of myocardial reperfusion. Echocardiography was performed
      3 and 180 days after pPTCA. End-diastolic volume (EDV), end-systolic volume (ESV)
      and ejection fraction were calculated. Patients were divided into three groups:
      group A (41 pts.) reperfused within 3 hours, group B (40 pts.) reperfused between
      3-6 hours, group C (25 pts.) reperfused between 6-12 hours from symptoms onset.
      RESULTS: MBG 0-1 (lack of myocardial reperfusion) was significantly more common
      in group B and C, compared with group A (p = 0.002). The incidence of nST was
      higher in group A (p < 0.0001). The EF after 3 days (p = 0.03) and after 6 months
      (p = 0.04) was better in group A in comparison to group C. There was not
      significant difference in EDV after 3 days, but after 6 months EDV was
      significantly higher in group C (p = 0.02). CONCLUSIONS: The delay of treatment
      over 3 hours is associated with decreasing of myocardial reperfusion efficacy and
      deterioration of the early and late LV function.

PMID- 15962606
TI  - [Effect of orlistat therapy on carbohydrate, lipid, vitamin and hormone plasma
      levels in obese subjects].
AB  - Orlistat is an inhibitor of lipase which splits triglycerides into free fatty
      acides and glycerol. This drug, by inhibiting hydrolysis of triglycerides, is the
      cause of significant loss of fat in the faeces. 13 obese and 15 nonobese subjects
      were examined. Obese subjects received orlistat (Xenical, F. Hoffmann La Roche
      Ltd, Switzerland) 3 x 120 mg/d. Treatment with orlistat for 16 weeks was followed
      by a significant fall of BMI and MAP, insulinemia, insulin/glucose ratio,
      leptinemia, serum total cholesterol, triglycerides, HDL-cholesterol and 25-OH-D
      concentration respectively. Orlistat did not influence significantly serum LDL
      cholesterol concentration but unexpectedly increased plasma levels of folic acid,
      vitamin B12 and NPY. CONCLUSIONS: (1) Monitoring of plasma 25-OH-D levels in
      obese patients on orlistat therapy seems to be mandatory. (2) In spite of
      significant changes (in opposite direction) in leptinemia and serum NPY level
      observed in obese subjects treated with orlistat, presence of a functional
      relationship between these hormones could not be confirmed.

PMID- 15962607
TI  - [Cardiovascular risk factors in dialyzed patients].
AB  - Cardiovascular complications are the main cause of mortality and morbidity among
      patients on dialyses. The aim of the work was to assess the effect of the type of
      renal replacement therapy on the risk factors and cardiovascular complication in
      dialyzed patients. The studies were performed retrospectively on 90 hemodialyzed
      and 49 peritoneally dialyzed patients. Risk factors of cardiovascular diseases as
      well as serum lipids, complete blood count, serum albumin, fibrinogen, C-reactive
      protein, calcium, phosphates, PTH, systolic, diastolic, mean blood pressure, left
      ventricular hypertrophy. Hemodialyzed patients were more anemic, longer on renal
      replacement therapy, with higher albumin, phosphates, lower fibrinogen,
      cholesterol, LDL, triglycerides, calcium, systolic and diastolic blood pressure
      than peritoneally dialyzed patients. Left ventricular hypertrophy more frequently
      found in hemodialyzed patients than in peritoneally dialyzed patients. In
      peritoneally dialyzed patients glucose load into the peritoneum, dyslipidemia and
      hiperfibrinogenemia may further contribute at the cardiovascular complications.
      In hemodialyzed patients anemia, left ventricular hypertrophy and ischemic heart
      disease is more frequent than in peritoneally dialyzed patients.

PMID- 15962608
TI  - [Factors influencing cardiac complications in patients with type-2 diabetes
      mellitus and silent myocardial ischaemia: five-year follow-up].
AB  - Silent myocardial ischaemia (SMI), a common disorder, has been studied by
      different research groups for the last 25 years. It is known that SMI is more
      common in patients with type 2 diabetes mellitus (type 2 DM) than in the general
      population, even though pathological mechanisms responsible for SMI are unclear.
      The aim of the study was to assess the role of SMI and other conditions in
      predicting adverse outcome in patients with type 2 DM during five years of follow
      up. MATERIALS AND METHODS: 67 males with type 2 DM were enrolled into the study
      group. 55-healthy men were used as a control group (CG). Precise clinical
      examinations (medical history, physical examination, laboratory tests) were
      conducted. Coronary risk factors and the level of diabetes control were assessed.
      Noninvasive cardiological tests: ETT, 24 h ECG and echocardiography were
      performed. The prevalence of the following complications: ischaemia, unstable
      angina, myocardial infarction, heart failure, death and need for invasive
      procedures was recorded for five years. Parameters responsible for the
      complications were analyzed with the use of univariate logistic regression test;
      odds ratio was calculated. RESULTS: The silent myocardial ischaemia was found in
      32.8% of patients with type 2 DM and in 9.1% men in control group (p < 0.001).
      The complications were observed in 24% of men with DM and in 16% in control group
      (NS). It was found that 25 parameters in the studied group and 16 parameters in
      the control group were statistically significant for the prediction of
      complications (among analyzed 92 parameters). The most important of them in type
      2 DM group are: duration of diabetes (years) OR--1.18 (p < 0.01), fasting glucose
      (mg/dl) OR--1.017 (p < 0.01), SMI episodes (ETT) OR--4.72 (p < 0.01), diastolic
      dysfunction (E/A), OR--0.003 (p < 0.02) and left ventricle hypertrophy OR--3.86
      (p < 0.05), whereas in CG--SMI episodes, OR--17.72 (p < 0.002). CONCLUSIONS: (1)
      The silent myocardial ischaemia is common in patients with type 2 DM. It was
      diagnosed in 33% of the patients. (2) The presence of SMI significantly increases
      the risk of complications both in patients with diabetes mellitus and the control
      group. (3) There are many other factors predisposing to the complications. In
      patients with diabetes mellitus they included, besides SMI, the duration of
      diabetes, chronic hyperglycemia and left ventricular diastolic dysfunction.

PMID- 15962609
TI  - [Anagrelide in the treatment of thrombocythemia essential (ET)].
AB  - Essential thrombocythaemia (ET), the most often occurring myeloproliferative
      disorder is a clonal malignant disorder arising from stem cell. The course of the
      disease is complicated by some severe thrombotic events and far less commonly by
      haemorrhagic phenomena. Treatment of ET consist of antiplatelet drugs (e.g.
      aspirin) and lowering platelet count (hydroxyurea or interferon alpha).
      Anagrelide (anagrelide hydrochloride) is an imidazoquinazoline derivative which
      lowers platelet count probably by inhibiting thrombopoiesis and reduces platelet
      aggregation. The aim of the study was to evaluate the efficacy and side effects
      of anagrelide in patients with ET refractory to prior treatment with hydroxyurea.
      Anagrelide (Agrylin or Thromboreductin) was used in 40 patients with ET from Jan.
      1999 to June. 2003. Out of 40 patients, there were 29 females and 11 males,
      (median age 52.0 +/- 14.25 years; range, 21-72). Median follow up was 23 months
      (range, 8 to 54 months). Anagrelide in the average dose of 2,0 mg (range, 1,0-3,5
      mg) reduced platelet count in all patients. Median time of response was 3-4
      weeks. Complete remission (platelet count < or =450 G/l) achieved 22 persons
      (55%) and partial remission 17 persons, and only one patient had platelet count
      slightly above 600 G/l (627 G/l). There was a significant (p < 0.05) reduction in
      platelet count from a mean of 1136.05 +/- 295.09 G/l to 480.98 +/- 72.26 G/l
      (56%) Despite platelet count reduction <500 G/l in 3 patients reappeared symptoms
      of low extremities deep venous thrombosis and in one transient ischaemic cerebral
      stroke was found. Hemoglobin level in a single case was lower than 12 g/dL (10.8
      g/dL), and neither leukopenia nor disturbances of hepatic or renal function were
      observed. During the first two months of treatment with anagrelide some mild and
      transient side effects were noticed, eg. headache in 10 (25%), fluid retention in
      8 (20%), palpitations in 4 (10%), and diarrhoea in 2 (5%) patients, but all of
      them continued therapy. Achieved platelet count reduction allowed in 2 ET
      patients safe performance of planned surgery (cholecystectomy, partial
      thyroidectomy) and in 1 balloon coronary angioplasty. Anagrelide proved to be an
      effective drug for of ET patients refractory to hydroxyurea.

PMID- 15962610
TI  - [Clinical, biochemical and hormonal characteristics of 84 patients with
      incidentally found adrenal tumor (incidentaloma)].
AB  - In this study we have analyzed 84 patients (58 women, 26 men, mean age 57 +/- 1.1
      year) hospitalized in the Department of Nephrology, Endocrinology and Metabolic
      Diseases of the Medical University of Silesia in Katowice from 01.01.1999 to
      30.04.2003 because of incidentally discovered adrenal tumors (incidentaloma). The
      diameter of the tumors ranged from 8 to 86 mm (mean size 35.4 +/- 1.8 mm).
      Unilateral tumors were found in 74 patients and bilateral ones in 10 patients. In
      all patients circadian rhythm of plasma cortisol concentration and urinary
      cortisol excretion were measured. In 73 patients with a history of hypertension
      plasma renin activity was estimated in basal conditions and after stimulation by
      sodium restriction and upright position. Aldosteronemia and urinary
      metoxycatecholamines excretion were also determined. 45 patients with tumors >4
      cm and/or with suspicion of malignancy or hormonal hypersecretion were qualified
      for surgical treatment. Thirty two patients out of the selected 45 have been
      operated so far. In two patients histopathological examination confirmed
      malignancy (adrenocortical carcinoma in one patient and metastatic cancer in the
      other one). The remaining 30 patients were operated because of size of the
      adrenal mass (16 patients) or biochemical suspicion of pheochromocytoma (12
      patients, 5 of them with the mass size >4 cm) or primary aldosteronism (2
      patients). The histological examination confirmed Conn syndrome in two patients
      and pheochromocytoma in one patient.

PMID- 15962611
TI  - [Six-month outcomes and prediction of mortality in 458 patients with acute
      coronary syndromes without persistent ST segment elevation assigned to early
      invasive strategy].
AB  - BACKGROUND: Utilization of early invasive strategy for patients with acute
      coronary syndromes (ACS) without persistent ST-segment elevation remains
      controversial. In this study we characterized a group of high-risk patients who
      underwent early invasive assessment and treatment. METHODS: We analysed 458
      consecutive pts who fulfilled following criteria: (1) rest angina within 24 hours
      prior to admission, (2) at least one of the following: ST-segment depression (>
      or = 0.05 mV), transient (> or =20 min) ST-segment elevation (> or = 0.05 mV), T
      wave inversion (> or =1 mV) in at least 2 contiguous leads, positive serum
      cardiac markers. All patients were diagnosed invasively with subsequent
      revascularization if appropriate. Analysis of long-term survival and occurrence
      of major adverse cardiovascular events requiring hospitalization (MACE) was
      performed. RESULTS: Baseline characteristics of the pts: Age: 61.5 +/- 10 years,
      males: 67.3%, diabetes: 19.6%, hypertension: 72.9%, smokers: 39.5%,
      hyperlipidemia: 78.6%, previous myocardial infarction: 50.4%, previous CABG 6.5%,
      previous PCI 14.4%. PCI was performed in 71.8% of pts, 18.2% underwent CABG, 1.3%
      had combined PCI and elective CABG and 8.7% of pts were treated conservatively.
      In-hospital and overall mortality was 3.3% and 4.8% respectively. MACE were
      observed in 20.3% of pts. Multivariate analysis identified two independent
      predictors of death: diabetes mellitus (OR: 6.01, 95% CI: 1.1-13.2, p = 0.04) and
      heart failure (OR: 11.6, 95% CI: 2.56-15.6, p = 0.005) and three predictors of
      combined endpoint (death, non-fatal myocardial infarction, repeat
      revascularization): male sex (OR: 3.33, 95% CI: 1.30-8.55, p = 0.01), previous MI
      (OR: 2.32, 95% CI: 1.07-5.03, p = 0.03) and PCI treatment of acute coronary
      syndrome (OR: 3.11, 95% CI: 1.39-6.98, p = 0.006). CONCLUSIONS: Early invasive
      strategy in high-risk ACS patients yields good long-term results with low
      mortality rate, especially during in-hospital observation. Diabetes mellitus and
      heart failure were independently associated with increased mortality rate,
      whereas male sex, previous MI and PCI during index hospitalization predicted
      major adverse cardiovascular events in 6-month follow-up.

PMID- 15962612
TI  - [28-year-old woman with Goodpasture's syndrome and nonspecific colitis].
AB  - Goodpasture's syndrome usually becomes manifest with progressive
      glomerulonephritis and pulmonary hemorrhage. The diagnostic hallmark is the
      demonstration of anti-basement membrane anti-alpha3 type IV collagen antibodies
      (anti-GMB antibodies) in patient sera. Herein is reported the case of 28-year-old
      woman with Goodpasture's syndrome who developed the acute symptoms of nonspecific
      colitis which required surgical intervention. Immunosuppression along with
      plasmapheresis was successful in the treatment of life-threatening pulmonary
      hemorrhage, but not for the improvement of renal function.

PMID- 15962613
TI  - [Simultaneous occurrence of autoimmune hepatitis type III and autoimmune
      thyroiditis type III (Graves disease)].
AB  - The case of simultaneous clinical manifestation of autoimmune hepatitis (AIH) and
      autoimmune thyroiditis was described. The authors presented diagnostic
      difficulties often related to AIH. The interdependence between the liver and
      thyroid gland function was emphasized. Correlative occurrence of different
      diseases of autoimmune origin in the same patients indicates a particular genetic
      predisposition.

PMID- 15962614
TI  - [First Polish experience with enzyme replacement therapy in patients with Fabry
      disease].
AB  - We report here the course and outcomes of 18-month enzyme replacement therapy in
      two 43 and 41-year-old brothers with Fabry disease. At 18 months of recombinant
      alpha-galactosidase A (Fabrazyme) infusions, we observed in the older patient:
      weight gain, decreased proteinuria (from 4 to 1.5 g/d), stabilization of
      creatinine clearance, much lower frequency and intensity of angina, and in the
      younger brother: weight gain, stabilization of creatinine clearance and
      proteinuria, prolongation of PQ interval and improvement of hearing. However,
      neurologic manifestations deteriorated over treatment period in both patients. No
      serious infusion-related side effects were observed.

PMID- 15962615
TI  - [Ageing and immune system].

PMID- 15962616
TI  - [Interleukin 3 (IL-3) and its clinical applications].

PMID- 15962617
TI  - [Low-carbohydrate, high-fat diets: efficacy and safety].

PMID- 15962618
TI  - [Adiponectin--common link in the pathogenesis of metabolic disorders and
      cardiovascular diseases?].

PMID- 15962619
TI  - [Inflammation of fat tissue--panniculitis. The clinical study--part I. The
      clinical picture of panniculitis and pathogenetic hypotheses].

PMID- 15962621
TI  - [Donating, a basic instinct?].

PMID- 15962620
TI  - [Inflammation of fat tissue--panniculitis. The clinical study--part II. Case
      reports].

PMID- 15962622
TI  - [Pre-travel advice for the elderly].
AB  - The aging population, the multiplication of leisure activities and the many
      possibilities to travel will confront the primary care physician to elderly
      travelers who want health advice prior to their journey, sometimes in remote
      areas. Age itself is no contra-indication to travel, but the co-morbidities and
      the potential upsets that the elderly can be submitted to might render her/him
      more vulnerable to health problems. A medical evaluation, specific
      recommendations about traveling (including sufficient medication and medical
      material) and a medical certificate should be proposed by the primary care
      practitioner to her/his elderly patient planning to travel.

PMID- 15962623
TI  - [Travelling when pregnant? possible, but...].
AB  - Travelling when pregnant? possible, but... Travelling when pregnant is possible.
      We recommend to travel during the 2nd trimester, avoid region of high malaria
      endemicity, choose destination where good medical service exist, check for
      adequate insurance coverage, favour comfortable type of travel, without long air
      or road transportation, avoid travelling if at risk pregnancy. For any
      vaccination or medication risks and benefits should be carefully weighed,
      pregnant women are more vulnerable and at higher risk of complications.

PMID- 15962624
TI  - [HIV and travel].
AB  - Since the introduction of antiretroviral therapy (ART), persons living with HIV
      (PLHIV) are traveling more frequently and international travel has become much
      safer. Specific concerns include the safety of ART during travel, drug adherence
      and interactions. The simultaneous administration of ART and antimalarial drugs
      is a challenge, considering the lack of reliable data. Several travel-related
      infectious diseases are more frequent and/or more severe in PLHIV. Even with a
      CD4 count > 400/microl, some PLHIV experience lower immune responses to several
      vaccines. With avanced immunosuppression, complications following the
      administration of live vaccines can occur, and most of the responses to vaccine
      are clearly reduced. The consequences of reduced vaccine immunogenicity on their
      clinical effectiveness (protection against infection) are unclear.

PMID- 15962625
TI  - [Diabetics travelling].
AB  - As anyone else, diabetic patients are confronted to professional or private
      travels. This article is meant to gather some practical recommendations to allow
      patients to travel safely. All travels must be thoroughly prepared and diabetes
      must stabilised at best before departure. To avoid severe hypoglycaemias and
      ketosis are the medical objectives. It is therefore essential that patients take
      with them their injection material and a sufficient carbohydrate back up. The
      prevention of diarrheas and vomiting, as well as the adaptation of treatment to
      jet-lag and all kind of physical activity are necessary to have a nice travel.
      Some specific aspects of travelling by car, boat or plane are discussed.

PMID- 15962626
TI  - [Pre- and post-exposure rabies prophylaxis: who to vaccinate and how?].
AB  - Switzerland is rabies free since 1996 (except bats). However sporadic cases in
      animals (imported dogs and local bats essentially) may occur from time to time.
      The disease is always fatal, which implies special attention when someone gets
      bitten or scratched by a wild or unknown animal, not only in a country with a
      high endemicity, but also in Switzerland. In this article, we will explore in
      detail the modalites of application of pre- and post-exposure prophylaxis
      following the publication of new recommandations from the Public Health
      authorites of Switzerland.

PMID- 15962627
TI  - [Diagnosis of malaria in general practice: dealing with uncertainty].
AB  - Malaria is the disease to exclude when dealing with a patient coming back from an
      endemic area with fever. We need reliable diagnostic tools with negative
      likelihood ratio (LR-) close to zero (-> high negative predictive value).
      Ideally, a microscopical examination (ME) (thick and thin film) should be done,
      with or without a rapid diagnostic test (RDT). When the ME is not immediately
      available, an RDT can be done in the practice office and the ME delayed for 6-12
      hours, provided there is no danger sign or thrombopenia. Indeed, the LR- of RDT
      being of 0.08 (estimated in a meta-analysis of RDT in non-immune travelers), the
      probability of falciparum malaria is 1% after a negative RDT. When the RDT is
      positive, the patient should always be treated with an anti-malarial, even if the
      ME is negative.

PMID- 15962628
TI  - [The right to know...and the duty to tell].

PMID- 15962629
TI  - [The right to know].

PMID- 15962630
TI  - [Cancer of the prostate: importance of androgen deprivation and radiotherapy].

PMID- 15962631
TI  - [Childhood hypertension: current medical management].
AB  - Pediatricians currently have improved understanding of how to best manage
      childhood hypertension. The goal of antihypertensive drug therapy in children
      with secondary hypertension is currently to reduce the blood pressure below the
      90th centile. Most authors currently favor therapy with a blocker of the renin
      angiotensin system (a converting enzyme inhibitor or an angiotensin II
      antagonist) or a calcium channel blocker. In patients with kidney disease and
      diabetes mellitus we generally advise therapy of hypertension with a blocker of
      the renin-angiotensin system especially in the presence of pathological
      proteinuria.

PMID- 15962632
TI  - [The engagement of sugar and television].

PMID- 15962633
TI  - ["Mental suffering," small French tragi-comedy (Act 4)].

PMID- 15962634
TI  - [Disheartened physicians].

PMID- 15962635
TI  - Adverse affects of paclitaxel and carboplatin combination chemotherapy in
      epithelial gynecologic cancer.
AB  - OBJECTIVE: To evaluate the adverse affects of paclitaxel and carboplatin
      combination chemotherapy. DESIGN: Descriptive cross sectional study MATERIAL AND
      METHOD: Patients with epithelial cancer of the ovary, fallopian tube and
      peritoneum treated with paclitaxel and carboplatin combination chemotherapy at
      Chiang Mai University Hospital between August 2003 and August 2004. RESULTS: Of
      224 evaluable cycles in 63 patients treated with paclitaxel (175 mg/m2) and
      carboplatin (AUC 5), grade 3 and 4 neutropenia occurred in 37.1% or 41.3% of
      patients. 4.8% of patients experienced febrile neutropenia. Grade 3 and 4
      leukopenia occurred in 8.6% of courses and 12.6% of patients. Grade 3 anemia
      occurred in 5.2% of courses and 9.5% of patients. Grade 3 thrombocytopenia
      occurred in 2.8% of courses and 9.6% of patients. The nonhematologic adverse
      affects were rare, however, some adverse events may be potentially life
      threatening. CONCLUSION: Adverse affects of paclitaxel and carboplatin
      combination chemotherapy are acceptable and manageable in the majority of
      patients.

PMID- 15962636
TI  - Changing physician's practice on antenatal corticosteroids in preterm birth.
AB  - This study aimed to monitor the change of practice in antenatal corticosteroids
      use in preterm birth, assess how physicians would prescribe and identify factors
      associated with such a prescription. Medical records were reviewed quantitatively
      and current attending physicians were interviewed qualitatively. Multiple
      logistic regression with random effect model was used for analysis. The results
      revealed that antenatal corticosteroid use in preterm births initially doubled
      after the evidence became available and tripled after the evidence was
      disseminated. The antenatal corticosteroid use among women having a gestational
      age less than 34 weeks increased significantly from 41% to 71% and 73%,
      respectively (p < 0.01). A gestational age of 34 weeks or more or a higher
      cervical dilatation at admission reduced the use of corticosteroids
      significantly. In conclusion, physician's practice changed based on the evidence.
      The education for the early recognition of labor and guidelines on the use of
      antenatal corticosteroids should be implemented.

PMID- 15962637
TI  - One year study of Implanon on the adverse events and discontinuation.
AB  - OBJECTIVE: To determine adverse events and discontinuation of Implanon in healthy
      Thai women between 16 and 45 years of age. DESIGN: Prospective descriptive study.
      SETTING: Family Planning Unit, Department of Obstetrics and Gynecology, Faculty
      of Medicine, Chiang Mai University. SUBJECTS: Ninety-two female volunteers with
      eligible criteria, no contraindication for hormonal contraceptive and wished to
      have long-term contraception were recruited. MAIN OUTCOME MEASURES: Determination
      of adverse events was done three months after Implanon insertion. Discontinuation
      of Implanon use was reviewed during the study period of one year RESULTS:
      Amenorrhea (40.2%) and infrequent bleeding (39.1%) were the most menstrual
      adverse events. While most non-menstrual adverse events were headache/dizziness
      (27.2%) and lower abdominal pain (23.9%). Severe non-menstrual side effect was
      rare (1-2%). Seven subjects (7.6%) discontinued using Implanon during the one
      year period of study. CONCLUSION: Implanon demonstrated a high continue rate at
      the first year of insertion. It produced similar adverse events like other
      progestin-only contraceptives. Counseling before insertion is important for
      increased client satisfaction and a higher continuation rate.

PMID- 15962638
TI  - Operative treatment of hepatic trauma in Vachira Phuket Hospital.
AB  - Descriptive study of an 8-year period, 211 patients with hepatic trauma were
      studied retrospectively. Most of the patients were male (81.5%). Patients mainly
      affected were in the third decade of life (46.9%) with an age range of 2 to 65
      years old (Mean 26.1 +/- 9.8). Fifty four percent resulted from blunt and 46.4%
      from penetrating injuries. The most common cause of injuries was motorcycle
      accidents (41.2%). The injuries were graded by the hepatic injury scale (grades I
      to VI). There were 22 (10.4%), 62 (29.4%), 70 (33.2%), 27 (12.8%), 28 (13.3%) and
      2 (0.9%) patients with grade I, II, III, IV, V and VI hepatic injuries,
      respectively. Forty seven percent of patients were in shock when they first
      arrived at the emergency room. One hundred and sixty five patients (78.2%) had
      375 associated injuries. Seventy three percent of patients had low grade hepatic
      injuries (grades I to III), the remainder (27%) had high grade hepatic injuries
      (grades IV to VI). Operative treatment of hepatic injuries varied according to
      degree of injury. Low grade hepatic injuries amenable to relatively simple
      operative treatment. Nineteen deaths (12.3%) occurring in this group were
      attributed to the commonly encountered associated injuries inside and outside the
      abdomen, which were more frequently seen after blunt trauma (89.5%). High-grade
      hepatic injuries required major techniques. Thirty four of these patients died
      (59.6%), death was related to the injury itself (91.2%), which were more
      frequently seen after blunt trauma (85%). During operation, suture ligature of
      the bleeding point, or hepatorrhaphy stopped the bleeding in most circumstances.
      Perihepatic packing was a useful procedure when termination of the operation was
      considered necessary in order to prevent the development of hypothermia, acidosis
      and coagulopathy. Perihepatic packing was used for treatment of 73% of high grade
      hepatic injuries and yielded 65.5% survival rate. The results were 59 patients
      had complication (morbidity 28%) and 53 patients in the present study died
      (mortality 25.1%). Thirty one patients (14.7%) died of hepatic cause, whereas 22
      patients (10.4%) died of non hepatic causes. Exsanguination and associated head
      injuries were the major cause of death (83%). Nonsurvivors had a significantly
      higher shock, blunt injury, associated injury and high grade hepatic injury than
      survivors (p < 0.005). The high mortality and morbidity can be achieved by well
      regulated motorcycle accident prevention measures and well prehospital care.

PMID- 15962639
TI  - Vaccination against hepatitis B virus: are Thai medical students sufficiently
      protected?
AB  - Medical students are frequently at risk of being infected by hepatitis B virus
      (HBV) via occupational exposure to infected blood or body fluids. In 2002, the
      Faculty of Medicine, Siriraj Hospital provided screening tests for HBV serology
      to all medical students for a vaccination campaign against the infection. There
      were 1,165 medical students tested. Eight hundred and eleven (69.6%) students had
      immunity by previous vaccination, but more importantly 212 (18.2%) had no
      immunity and required vaccination. Most of the students who needed to be
      vaccinated were in the pre-clinical year (82.5%). Moreover, the students in the
      pre-clinical year who had previous vaccination had a 2.2 times greater risk of
      having negative anti-HBs than the students in the clinical year (OR = 2.2, 95% CI
      = 1.4-3.5). This is because they might have been vaccinated when they were young
      and the antibody waned overtime.

PMID- 15962640
TI  - Estimated economic losses of hospitalized AIDS patients at Siriraj Hospital from
      January 2003 to December 2003: time for aggressive voluntary counseling and HIV
      testing.
AB  - This retrospective study was performed to explore the pattern of adult HIV
      infected patients admitted to Siriraj Hospital from January 2003 to December 2003
      and estimated the economic losses of these patients. Two hundred and forty four
      medical records were available for review. The proportion of male to female was 2
      to 1. Mean age of patients was 36.64 +/- 9.72 years. The mean CD4 count among 112
      patients was 82.79 +/- 96.49 cell/mm3. One hundred and twenty four (50.82%) were
      newly diagnosed of HIV infection. The three most common opportunistic infections
      were Tuberculosis (42.62%), Pneumocystis carinii pneumonia (14.75%), and
      cryptococcosis (13.11%). The mean duration of admission was 15.72 +/- 15.11 days.
      The mean expense per admission was 38,194.58 +/- 32,354.86 Baht. Fifty four
      patients (22.13%) died during admission. The mean income of these patients was
      3,903.5 +/- 3,841.42 baht per month. The estimated economic losses of 54 patients
      who died during admission including medical care expense and income losses due to
      premature death was 69,769,739.32 baht. However, the expected medical expense of
      antiretroviral medications in these 54 patients if they had been diagnosed
      earlier and their lives had been saved would have been 42,214,608 baht.
      Therefore, vigorous voluntary counseling and HIV testing in patients aged 13-70
      years when they have any risk factors for HIV infection regardless of symptoms
      might be more cost effective than diagnosis when they get sick.

PMID- 15962641
TI  - Tonometry after laser in situ keratomileusis treatment: a preliminary study in
      Thai patients.
AB  - OBJECTIVE: To evaluate the change in intraocular pressure (IOP) measurement by
      Goldmann applanation tonometer after Laser in Situ Keratomileusis (LASIK) for
      myopia and myopic astigmatism, and to assess the correlation between the changes
      of lOP reading and the reduction of central corneal thickness (CCT) after LASIK
      in Thai patients. STUDY DESIGN: Prospective correlational study. MATERIAL AND
      METHOD: LASIK was performed on 65 eyes of 33 patients for correction of myopia
      and myopic astigmatism. IOP was measured by Goldmann applanation tonometer before
      and 3 months after LASIK. The correlation between the change in IOP reading and
      the change in central corneal thickness were evaluated. RESULTS: IOP reading was
      significantly reduced by mean of 2.9 +/- 2.5 mmHg (p = 0.0001). The authors used
      Pearson analysis to study the correlation between the change in IOP and the
      reduction of CCT. In subgroup analysis the patients were divided by degree of
      myopia: group 1, myopia less than -3 diopters (D) (n = 14); group 2, myopia -3 to
      -6 D (n = 31); group 3, myopia greater than -6 D (n = 20)). The result showed
      more correlation in higher myopia group (Pearson; r = 0.158 in group 3, r = 
      0.098 in group 2 and r = -0.102 in group 1). CONCLUSION: Goldmann applanation
      tonometry underestimates the IOP in thin cornea. Variability in CCT is a potent
      confounder of this tonometry technique. Therefore, it has important implications
      for considering CCT measurement incorporated with Goldmann applanation tonometry
      for glaucoma diagnosis especially in myopic patients who undergo LASIK surgery.

PMID- 15962642
TI  - Retrobulbar injection of triamcinolone in thyroid associated orbitopathy.
AB  - OBJECTIVE: To identify the result of retrobulbar triamcinolone injection in
      patients with thyroid associated orbitopathy MATERIAL AND METHOD: Prospective
      noncomparative pilot study in 27 eyes of 19 patients who had been diagnosed as
      thyroid associated orbitopathy during October 2000 through April 2002. The
      patients received retrobulbar 40 mg triamcinolone treatment for each orbit
      weekly, totaling 4 applications. RESULTS: Three months after treatment, most of
      the patients demonstrated no significant change in visual acuity and visual
      field. Improvement of proptosis was observed in 15 eyes (56%) and stable in 10
      eyes (37%). Seven patients (41%) had improvement of extraocular muscle function
      as demonstrated by Hess test. These results remained stable in the majority of
      patients at the 6 months follow up period. No systemic side effects were observed
      The only significant local side-effect was intraocular pressure elevation which
      was found in 8 eyes and responded to antiglaucoma therapy. CONCLUSION: This
      preliminary study demonstrated the potential benefit of retrobulbar triamcinolone
      injection in cases of thyroid associated orbitopathy. Long-term study in these
      patients is required.

PMID- 15962643
TI  - Nondiagnostic core needle biopsy of the breast under imaging guidance: result of
      rebiopsy.
AB  - OBJECTIVE: To determine the rate and the clinical application of recommendation
      for repeat biopsy after core needle biopsy (CNB) under imaging guidance and to
      determine the result of rebiopsy. MATERIAL AND METHOD: A retrospective review was
      performed in 1,306 consecutive women who underwent core needle biopsy under
      imaging guidance at the breast diagnostic center, the Faculty of Medicine,
      Ramathibodi Hospital from October 1997 to March 2004. RESULTS: Among 1,306
      patients, there were 44 patients (3.37%) who had undergone rebiopsy. The three
      most common reasons for recommendation of rebiopsy were discordant imaging and
      pathology, atypical ductal hyperplasia and inadequate specimen. The authors found
      12 malignancies subsequently found in rebiopsy (27.3%). The most common reason
      for rebiopsy in this group was inadequate specimen. CONCLUSION: Core needle
      biopsy under imaging guidance is a minimally invasive diagnostic tool and
      promises high accuracy and reliability. However, some patients need rebiopsy to
      exclude hidden malignancy. The cooperation between the radiologists, surgeons and
      pathologists are prudent for giving the best care to the patients.

PMID- 15962644
TI  - Single dose oral clonidine premedication does not enhance postoperative, single
      low dose epidural morphine analgesia in hysterectomy patients.
AB  - In this randomized, double blind placebo controlled study, the authors evaluated
      the effects of oral clonidine premedication on very low dose epidural morphine
      analgesia in 50 hysterectomy patients. Patients were randomized to receive a
      single oral clonidine 300 microg (n = 25) or a placebo (n = 25) 90 minutes before
      insertion of the epidural catheter. 3 ml of 2% lidocaine with adrenaline (5
      microg ml(-1) mixed with 2 mg morphine were injected via epidural, followed by an
      additional volume of 2% lidocaine with adrenaline (5 microg ml(-1)) titrated to
      T6 block height before commencing general anesthesia. The postoperative analgesia
      regimen was 2 mg of intravenous morphine every 10 minutes for the first 48 hr and
      1 gm of oral acetaminophen every 4-6 hr after initiation of oral diet at 24-48 hr
      as required. Morphine consumption, acetaminophen, pain scores, and side effects
      were recorded thoughout 48 hr after surgery. The results show patients in the
      clonidine and placebo groups were not different in terms of local anesthetics
      dose (p = 0.27), total morphine and acetaminophen requirement (p = 0.34, p = 0.1)
      respectively. Pain scores at rest and movement were also not different in both
      groups (p = 0.83, p = 0.64) respectively. No serious adverse effects were noted.
      The authors concluded that oral clonidine approximately 6 microg kg(-1) does not
      enhance the analgesic effect of epidural morphine 2 mg after hysterectomy.

PMID- 15962645
TI  - Correlation between symptoms and urodynamic findings in Thai female patients with
      urinary incontinence.
AB  - OBJECTIVE: To determine the accuracy of a urinary incontinence questionnaire in
      the diagnosis of various types of urinary incontinence classified according to
      the results of multichannel urodynamic testing. MATERIAL AND METHOD: Between May
      2000 and April 2004, 129 women with symptoms of urinary incontinence were
      interviewed using a urinary incontinence questionnaire consisting of 12 urinary
      symptoms questions. Various patient demographic and other descriptive data were
      also collected. All patients underwent multichannel urodynamic testing, and
      classified using the International Continence Society criteria. Descriptive data
      and patient symptoms were tested for statistical association with the types of
      urinary incontinence. Sensitivity and specificity were used to measure the
      accuracy of the symptoms in distinguishing between the various urodynamic
      conditions. RESULTS: Of the 12 questions, only three questions (two stress
      incontinence symptoms and one overactive bladder symptom) were significantly
      associated with the urodynamic diagnoses of genuine Stress Urinary Incontinence
      (SUI) and Detrusor Overactivity (DO). The sensitivity and specificity for
      distinguishing between genuine SUI and DO from other urodynamic diagnoses or
      between each other were relatively low. CONCLUSION: Symptoms of urinary
      incontinence were not sufficient to predict types of urinary incontinence.
      Therefore, the authors suggest that urodynamic testing is still essential in the
      diagnosis and management of female urinary incontinence.

PMID- 15962646
TI  - The efficiency of different adjunct techniques for regional anesthesia.
AB  - In the present prospective, randomized controlled trial, 110 unpremedicated
      patients undergoing orthopedic surgery under regional anesthesia were randomly
      divided into 5 groups, with 22 patients in each. During the operation, group 1
      listened to a pre-recorded explanation and music, group 2 listened to a
      subliminal sound, group 3 received propofol by patient-controlled sedation (PCS),
      group 4 received intravenous midazolam, and group 5 was the control group.
      Patients in the midazolam group were significantly more sedated than the control
      group at 1 hr into the operation. The group that listened to an explanation and
      music were significantly less satisfied than the propofol group at the end of the
      operation and 30 min. postoperatively. An incremental cost-effectiveness ratio
      showed that if explanation and music are used instead of propofol it would save
      299.53 baht per patient, but the patient satisfaction score will be 17.26 points
      lower than if the more expensive drug is used.

PMID- 15962647
TI  - Aural rehabilitation for deaf children: a northeastern Thailand experience.
AB  - Aural rehabilitation for deaf children (hearing loss > 90 dB) has been
      established since World War II. Many developed countries such as USA, Canada,
      United Kingdom, Netherlands and Australia have famous institutes providing aural
      rehabilitation for these children so that they are able to communicate with other
      people in the hearing society. Teaching programs include auditory training,
      speech stimulation, speech correction and developing language skills by using
      natural conversation and real models. In Thailand, the most common mode of
      communication for deaf children is total communication which focuses on sign
      language, thus, limiting the ability to communicate with other people. With the
      realization of this problem, the preschool program for deaf children was set up
      in 1993 by an audiologist and a speech pathologist at the speech and hearing
      clinic, Department of Otolaryngology, Faculty of Medicine, Khon Kaen University.
      A study of 31 deaf children with the average better ear hearing threshold of 103
      dB (103.5 +/- 7.01), who visited the program regularly showed that it took an
      average of 277 days or approximately 9 months (9.25 +/- 4.1) after hearing aid
      fitting, in acquiring spontaneous meaningful single words or 638 days or
      approximately 21 months (21.3 +/- 4.3) in acquiring simple conversation or
      sentences of more than three words. The limitation and problems of the program
      will be discussed.

PMID- 15962648
TI  - Management of life threatening hemorrhage from facial fracture.
AB  - Persisted bleeding from facial fractures after nasal packing or direct pressure
      is not common, however if it happens, the mortality rate is very high. The study
      of the treatment for this group of surviving patients was made to find the
      guideline for management of these patients. From the period of 1 January 1993 to
      31 December 2002, 3756 cases of facial fractures were treated at the Trauma
      Center, Faculty of Medicine, Siriraj Hospital. There were 14 life-threatening
      hemorrhage cases and 9 patients survived. They were 3 Le Fort fracture, 2 nasal
      fracture, 1 mandibular fracture and 3 multiple facial fractures. Repacking of
      nasal cavities was performed and was able to stop bleeding successfully in 2
      cases. Three cases required operation and 3 cases had angiography and
      embolization. One case still bled after operation and needed angiography and
      embolization. The present study shows that the adequacy of nasal packing or wound
      compression should be evaluated first. Early operation could stop bleeding in
      nearly half of the cases. Angiography and embolization can be used alone or
      adjunct to the operation to control bleeding with good result.

PMID- 15962649
TI  - Sentinel node localization in breast cancer using intradermal dye injection:
      results, influencing factors and learning curve.
AB  - To evaluate the identification rate, false negative rate, concordance, negative
      predictive value of sentinel node localization in breast cancer using intradermal
      isosulfan blue injection whether this is accurate enough for surgical approach in
      breast cancer surgery and whether there is a significant learning curve for this
      technique. Factors affecting the outcomes of the procedure are also determined.
      From August 2002 to September 2003, 66 cases of stage 0-IIIB operable breast
      cancer patients underwent sentinel lymph node biopsy before standard breast
      cancer operation. Overall, identification rate was 80.3%, false negative rate was
      10.6%, concordance was 86.8%, negative predictive value was 83.3%, sentinel node
      was the only node that was positive in 45.5%, and mean operative time was 55.1
      minutes. Factors found to lower sentinel node identification rate are neoadjuvant
      chemotherapy and large tumor (T3-4) while previous excision was not found to
      affect the identification rate. There is significant learning curve in this
      technique and this should be performed at least 40-45 cases in the learning phase
      to accomplish a high identification rate and lower false negative rate before
      implicating into clinical practice.

PMID- 15962650
TI  - A test strip IgM dot-ELISA assay using leptospiral antigen of endemic strains for
      serodiagnosis of acute leptospirosis.
AB  - A test strip IgM dot-ELISA assay for the detection of leptospire-specific IgM
      antibodies in human sera was developed. Antigen dotted on a nitrocellulose paper
      strip was the pool sonicated antigen prepared from three predominant reactive
      Leptospira serovars currently in endemic area, i.e., Bratislava, Sejroe and
      Pyrogenes. The ability of the test to diagnose acute leptospiral infection was
      assessed by testing 343 single serum samples from 96 laboratory-confirmed
      leptospirosis case patients with positive result in the standard microscopic
      agglutination test (MAT), 55 serum samples from patients with various diseases
      other than leptospirosis, and 192 serum samples from healthy individuals. Using
      the results of the MAT as a gold standard, the sensitivity and specificity of the
      test strip IgM dot-ELISA assay were 98.96 and 93.93 per cent, respectively. The
      assay offered relatively high negative predictive values (99.57%) thus making the
      assay ideally suited for rapid screening. The stability of the test strip was
      assessed with a panel of five positive and five negative control sera after
      storage at 4 degrees C and -20 degrees C at different times. The results showed a
      good performance of the test strip at both storage temperatures for up to one
      year. In conclusion, the test strip IgM dot-ELISA assay was sufficiently
      sensitive for use as a screening test for serodiagnosis of acute leptospirosis.
      The assay was simple, inexpensive, and easy to perform for both a single test
      format and a large number of specimens. However, further studies are still needed
      to improve the stability of the test strip and assay reagents at ambient
      temperature, and to make the assay more rapidly and more user friendly.

PMID- 15962651
TI  - Randomized trial of atorvastatin in improving endothelial function in diabetics
      without prior coronary disease and having average cholesterol level.
AB  - OBJECTIVE: The aim of this study was to determine whether HMGCoA reductase
      inhibitor with atorvastatin can modulate endothelial function in type II
      diabetics having average cholesterol and no prior cardiovascular disease.
      MATERIAL AND METHOD: Type II diabetics, with no prior cardiovascular events and
      total cholesterol at admission of < or = 200 mg/dl or LDL < or = 140 mg/dl, were
      randomized to placebo (n = 20) or atorvastatin 20 mg daily (n = 22) for 30 weeks.
      Brachial artery endothelium-dependent dilatation or flow-mediated dilatation
      (FMD) and endothelium-independent dilatation or nitroglycerine-mediated
      dilatation (NTGMD) were measured at baseline and after thirty weeks of treatment.
      RESULTS: Baseline clinical characteristics were similar at admission in both
      groups. After thirty weeks of treatment, the FMD did not significantly change in
      either the atorvastatin or placebo group (4.11 +/- 1.05% to 3.01 +/- 1.27% vs
      5.75 +/- 1.93% to 6.45 +/- 1.41%, respectively; p = 0.46 by analysis of
      covariance). Similarly, the NTGM did not change in either group. CONCLUSION: The
      addition of HMGCoA reductase inhibitor with atorvastatin did not improve
      endothelial function in type 2 diabetes having average cholesterol with no prior
      cardiovascular disease, despite an improvement of the lipid profile.

PMID- 15962652
TI  - Reliability of the Roland - Morris Disability Questionnaire (Thai version) for
      the evaluation of low back pain patients.
AB  - OBJECTIVE: To determine the reliability of the Thai version of the Roland -
      Morris disability questionnaire in low back pain patients. MATERIAL AND METHOD:
      To develop Thai version of the Roland - Morris disability questionnaire and test
      it in 120 low back pain patients. Reliability of the Thai version of the Roland -
      Morris disability questionnaire was assessed by internal consistency using
      Cronbach's alpha coefficient. RESULTS: The overall Cronbach's alpha coefficient
      of the scale was 0.83. The Cronbach's alpha coefficient of each question in the
      Thai version of the Roland - Morris disability questionnaire exceeded 0.7 (range,
      0.71- 0.93). The Cronbach's alpha coefficient tested in acute or chronic low back
      pain patients whether they have back pain only or back pain with radiculopathy
      which also exceeded 0.7 (range, 0.83-0.87). CONCLUSION: The Thai version of the
      Roland - Morris disability questionnaire is a reliable tool for assessing
      functional disability of low back pain in Thai patients.

PMID- 15962653
TI  - Cross-validation of a self-report scale for postoperative pain in school-aged
      children.
AB  - The present study cross-validated self-report pain scales: Verbal Rating Scale
      (VRS), Facial Expression Scale (FACES), Color Analogue Scale (CAS) and Poker Chip
      Tool (PCT) in Thai children aged 5-12 years. The concordance with observational
      measure, Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) was also
      tested. Among 100 students, test-retest reliability of all self-report measures
      was moderate to good (K = 0.501-0.712) and only FACES yielded acceptable face
      validity(IC > 0.5). Validation in 87 patients, all scales showed construct and
      concurrent validity. FACES was the most preferred scale. Agreement of self-report
      measures and CHEOPS was better in the age group 5-8 years (K = 0.417-0.826) than
      9-12 years (K = 0.231-0.529). In conclusion, FACES is a valid, reliable and
      practical tool. Self-report measures are more in concordance with CHEOPS in the
      younger age group.

PMID- 15962654
TI  - Six criteria for rabies diagnosis in living dogs.
AB  - OBJECTIVE: The authors studied the predictive value of six criteria for clinical
      diagnosis of rabies in living dogs. DESIGN: Identify and test the criteria in a
      retrospective and prospective study. MATERIAL AND METHOD: Both studies were
      conducted at the Rabies Diagnostic Unit, Queen Saovabha Memorial Institute, Thai
      Red Cross Society, Bangkok. The authors reviewed 1,170 dogs that were kept under
      observation for 10 days after they exhibited abnormal behavior. To test the
      predictive value of the six criteria, a prospective study involving 450 rabies
      suspected dogs was also performed. RESULTS AND CONCLUSION: The six criteria
      demonstrated 90.2% sensitivity, 96.2% specificity and 94.6% accuracy for the
      clinical diagnosis of rabies. They can be used for a presumptive diagnosis and
      may help in prioritizing post-exposure treatments and institute urgent rabies
      control measures.

PMID- 15962655
TI  - Spontaneous resorption of an insect hair in the corneal stroma: a case report.
AB  - A case of keratitis, due to an insect hair penetrating into the deep cornea, was
      reported. The patient felt right ocular pain while riding a motorcycle, as an
      insect struck into his eye. On examination, an insect hair was seen embedded into
      the corneal stroma with severe corneal edema, which caused a visual acuity of the
      right eye decreased to hand motion. The patient was treated by a topical
      antibiotics, cycloplegics, and anti-inflammatory drugs, without removing the
      hair. After a 6-week follow-up period, there was a spontaneous resorption of the
      hair. There was no apparent toxic sign during 6-months of follow up, and the
      visual acuity improved to 6/6. The insect hair could be left in the deep cornea
      with careful observation, and spontaneous resorption can occur.

PMID- 15962656
TI  - A case report of infant with left ventricular noncompaction.
AB  - Left ventricular noncompaction (LVNC) is a rare cardiomyopathy resulting from
      abnormal arrest during endomyocardial embryogenesis. The authors present a 6
      month-old infant with intractable cardiogenic shock and echocardiographic
      features of LVNC, characterized by excessively prominent ventricular
      trabeculation and deep intertrabecular recesses as the first case report in
      Thailand.

PMID- 15962657
TI  - Bilateral Kuttner tumor of submandibular glands; a case report and review of the
      literature.
AB  - Kuttner tumor is a relatively uncommon disease of the salivary gland. It is also
      known as chronic sclerosing sialadenitis or cirrhosis of the submandibular gland.
      The examination of the submandibular gland characterizes clinically by a firm
      swelling of the gland, and histologically by progressive periductal sclerosis,
      dense lymphocytic infiltration with lymphoid follicle formation, reduction of the
      secretory gland parenchyma and fibrosis. Clinical, cytologic, histopathologic and
      immunohistopathologic features with briefly reviewed relevant literature
      describing 231 cases are discussed. The patients with the mean age of 44 years
      (range 13-81 years) had submandibular masses known to be present for 1 week to 55
      years (mean 23.2 years). There is a slight predilection for occurrence in men.
      This is the first reported description of bilateral Kuttner tumor of
      submandibular glands in Thailand. It was initially diagnosed as a primary
      submandibular gland neoplasm that fine needle aspiration revealed to be chronic
      sialadenitis.

PMID- 15962658
TI  - Concomitant dengue infection and Kawasaki disease in an infant: a case report and
      literature review.
AB  - A previously healthy 11-month-old girl presented with fever and rash for 6 days.
      Physical examination revealed an irritable infant with a high fever, injected
      conjunctivae, red cracked lips, posterior auricular lymphadenopathy,
      hepatomegaly, generalized erythematous maculopapular rash and petechial
      hemorrhage on trunk, face and extremities. Complete blood count showed atypical
      lymphocytosis and thrombocytopenia. Dengue infection was initially diagnosed. The
      persistent fever and clinical manifestations of Kawasaki disease (KD) were
      observed on day 8 with high erythrocyte sedimentation rate (56 mm/hr). Treatment
      of KD included intravenous immunoglobulin on day 9 of the illness. Desquamation
      of the fingers was found on day 15 of the illness. Ectasia of left coronary
      artery with small aneurysmal dilatation was detected by echocardiography on day
      15 of the illness. Hemagglutination-inhibition test and enzyme-linked
      immunosorbent assay for dengue virus eventually showed a four-fold rising.
      According to the literature review, this is the second reported case of dengue
      infection concomitant with KD. The natural course of each disease may be modified
      and causes some difficulties in diagnosis and management.

PMID- 15962659
TI  - Searching for medical ethics in Dharma conversation.
AB  - Our medical ethics team has a great opportunity to consider the terminology
      of"Moral Rights", "Good guys", "Understanding the real world" and the issues
      about "live salvation". What has been mentioned about these terms in Buddhism? In
      Buddhism, it has been cited that moral duty is the cause that leads to the moral
      rights as result. When we act the right as well as decent things, we are entitled
      to get the fair deals in return. We used to forget to consider that, isn't our
      moral duty or not?, to just either pay respect to the other people's rights or
      simply protect the other people's rights. Regarding to the Buddhism religion,
      there are a certain criteria to be "Good guys" i.e. firstly, not to make any sin
      at all such as not to exploit the others physically, verbally and mentally.
      Secondly, to make merits, such as helping out; showing the mercy and kindness to
      the underprivileged; donating money, land and properties, or even sharing the
      justified idea is also included. We also forgot to ask about tempting the others
      with a certain of hindrance i.e. assets, land and properties. Have you already
      made the sin with these temptations or dominating the idea of people? How the
      people will understand the fine line between the sin and meritorious deed?
      Buddhism kindly advises us to understand and consider the real world in two steps
      as well as in parallel way. Looking around us as surrounding of illusion. These
      illusion or fantasies will not be sustainable, only temporarily indeed. For
      example, human being has to go through aging process, illness and eventually
      death. What we need to consider in parallel is the matter about "Within us". What
      is the secret issue about "Within us"? Brain, spirit, heart or extremities,
      wherever we point at, will be just only human biological tissues or various
      elements. Last, but not least, practicing salvation when you still alive is
      perplexing. Live salvation is already existed within us, nowadays. No need to
      wait for the next life. Salvation can exist when we still alive. Salvation is to
      purify our spirit which require proper training to keep it clean in sustainable
      way.

PMID- 15962660
TI  - Prevalence and management of abnormal pap smear in antenatal care clinic at
      Thammasat University Hospital.
AB  - OBJECTIVE: To investigate the prevalence of abnormal Papanicolaou smear in
      pregnant patients who attend the Antenatal Care Clinic at Thammasat University
      Hospital. MATERIAL AND METHOD: Pregnant patients who attended the antenatal care
      clinic at Thammasat University Hospital from August 2003 to December 2003 were
      recruited for Papanicolaou test. Patients who had abnormal results of equally or
      over "abnormal squamous/glandular cells of undetermined significance" were
      assigned for colposcopy and colposcopic biopsy to confirm the result. RESULTS:
      From 500 Papanicolaou smear performed, there were only four patients who had
      abnormal Pap tests, which were: 2 ASC-US and 2 LSIL. The prevalence of abnormal
      Pap smear in pregnant patients who attended the antenatal clinic at Thammasat
      University Hospital was 0.8 percent. CONCLUSION: The prevalence of abnormal
      Papanicolaou smear in pregnant patients attending antenatal care clinic at
      Thammasat University Hospital was quite low in compares with other literature.

PMID- 15962661
TI  - Screening of cervical neoplasia by using pap smear with speculoscopy compared
      with pap smear alone.
AB  - OBJECTIVE: The objective was to compare the sensitivity and specificity of Pap
      smear plus speculoscopy with Pap smear alone. MATERIAL AND METHOD: The study was
      conducted in the Gynecology Clinic, Rajavithi hospital, Thailand between February
      1st and July 31st 2003. Women who made a request for cervical screening underwent
      a Pap smear, speculoscopy and colposcopy. Colposcopically directed biopsies were
      obtained from women who had a positive colposcopy. Analytical methods were
      applied. RESULTS: Of 257 women recruited to the study, Pap smear plus
      speculoscopy could increase sensitivity from 6.67% with Pap smear alone and to
      33.33% when Pap smear plus speculoscopy is used. The false negative rate was
      reduced from 93.33% with Pap alone and to 66.67% with Pap smear plus
      speculoscopy. In using Pap smear alone compared with combination of two tests,
      the specificity decreased from 97.52% to 77.68% and false positive rate increased
      from 2.48% to 22.31%, respectively. CONCLUSION: Adding speculoscopy to the Pap
      smear is able to significantly increase the sensitivity of the cervical
      screening. It also reduces the 'false negative" result. However, as expected, the
      specificity slightly decreases, due to the false positive from speculoscopy
      itself. One solution is to defer colposcopy for 6 months and to perform
      colposcopy only if either Pap smear or speculoscopy is positive.

PMID- 15962662
TI  - Feto-maternal hemorrhage after cordocentesis at Maharaj Nakorn Chiang Mai
      Hospital.
AB  - OBJECTIVE: To evaluate the incidence and volume of feto-maternal hemorrhage
      following cordocentesis. STUDY DESIGN: Descriptive study. MATERIAL AND METHOD:
      One hundred and sixteen asymptomatic non-anemic pregnant women with an indication
      for cordocentesis at 18-22 weeks of gestation between January and June 2004 were
      recruited. Maternal blood samples were obtained immediately before and 30 minutes
      after cordocentesis. Fetal cells in the maternal blood were counted using
      Kleihauer Betke test. About 25,000 maternal cells per slide were scanned by the
      same examiner. Feto-maternal hemorrhage was considered significant if the fetal
      bleeding was more than 0.25 ml. RESULTS: There was a significant increase in
      fetal blood volume in maternal circulation after cordocentesis (Paired Students t
      test, p < 0.001). A significant hemorrhage (> 0.25 ml) occurred in 63 from 116
      women (54. 7%). Only one had marked hemorrhage of more than 5.0 ml and none had
      massive hemorrhage (> 15 ml). CONCLUSION: Cordocentesis at 18-22 weeks of
      gestation can be associated with feto-maternal hemorrhage in more than half of
      the cases but nearly all cases had only minimal hemorrhage and none had massive
      hemorrhage.

PMID- 15962663
TI  - Risk factors for early infection after an acute cerebral infarction.
AB  - BACKGROUND AND OBJECTIVE: Infection is a common complication after an acute
      stroke. This is important because it may cause death or delayed successful
      rehabilitation. Investigation of the risk factors for infection after an acute
      stroke is limited The objective of this study was to determine the risk factors
      for early infection after an acute cerebral infarction. DESIGN: Retrospective
      analystical study. MATERIAL AND METHOD: The medical records of patients admitted
      within 48 hours of onset of symptoms to Prasat Neurological Institute from 1
      January 2002 to 31 December 2003, with a diagnosis of cerebral infarction,
      confirmed with CT or MRI of the brain were retrospectively studied. Collected
      data included clinical features, risk factors for stroke, comorbid conditions,
      infection, and results of diagnosis tests. Univariate and multiple logistic
      regression analyses were used to determine factors that were associated with the
      risk of early infection. RESULTS: During the 24-month study period, 332 cerebral
      infarct patients were identified. Early infection occurred in 7.6%. The most
      common infection was pneumonia (4.3%). In the final multiple logistic model,
      independent risk factors for early infections were atrial fibrillation (OR, 9.31;
      95% CI, 2.18-39.75), thromboembolic infarction (large vessel disease) (OR, 6.04;
      95% CI, 1.97-18.54), admission conscious level (subconscious or unconscious/coma)
      (OR, 4.82; 95% CI, 1.60-14.55) and previous stroke (OR, 3.20; 95% CI, 1.21-8.47)
      respectively. CONCLUSION: Atrial fibrillation, thromboembolic infarction (large
      vessel disease), admission conscious level (subconscious or unconscious/coma),
      and previous stroke were independent risk factors for development of early
      infection.

PMID- 15962664
TI  - The correlation of left ventricular hypertrophy with the severity of
      atherosclerosis and embolic events.
AB  - OBJECTIVE: The study was undertaken to assess the correlation between the
      presence and degree of aortic atheroma with degree of Left ventricular (LV) mass
      index and subsequent clinical outcomes. MATERIAL AND METHOD: The authors studied
      the clinical profiles of 87 patients with aortic atherosclerosis and controls,
      who had undergone TEE between 1995 and 2000. RESULTS: Mean LV mass index was 116
      gram/m2 in atherosclerosis group compared to 81 gram/m2 in the control group (p <
      0.009). In the atherosclerotic group, there was a close correlation between LV
      mass index score and severity of the plaque in the aortic arch and descending
      aorta (p < 0.001, 0.001). The presence of large ulcerated plaque had a
      significant correlation with stroke (p < 0.002). CONCLUSION: 1) LV mass index
      correlates with the severity of aortic atheroma. 2) Smoking, elevated mean
      arterial blood pressure and a high LV mass index score are significantly
      correlated with large ulcerated plaque and stroke. 3) These findings may in part
      explain the higher cardiovascular risk in patients with increased left
      ventricular mass.

PMID- 15962665
TI  - Preoperative chemoradiotherapy in locally advanced rectal cancer: Ramathibodi
      experience.
AB  - A retrospective study of the preoperative chemoradiotherapy in locally advanced
      rectal cancer performed at Ramathibodi Hospital. The median age of twelve
      patients was 52 years. The tumor locations (upper-, mid-, lower rectum) were 25%,
      50% and 25%, respectively. Eleven patients had clinical stage 111 disease. All
      received concurrent 5-FU-based chemoradiotherapy followed by surgery (if
      resectable) and chemotherapy. The most common toxicity of preoperative treatment
      was gr. 1-2 diarrhea (58.3%). The response rate was 41.7%. Five patients (41.7%)
      underwent sphincter-sparing surgery. Four patients underwent AP resection. Twenty
      five percent achieved pathological complete response. Pathological downstaging
      occurred in 33.3%. The remaining three patients had unresectable disease. With
      the median follow up of 13 months, five patients had progressive disease and one
      has expired. The local failure rate was 16.7%. The one-year recurrence-free
      survival was 75%. The authors conclude that preoperative chemoradiotherapy is an
      effective treatment with favorable outcome in locally advanced rectal cancer.

PMID- 15962666
TI  - Growth of breast-fed and formula-fed infants compared with national growth
      references of Thai children.
AB  - OBJECTIVE: To compare the growth patterns of breast-fed (BF) and formula-fed (FF)
      infants with national growth references of Thai children and to determine whether
      the Thai growth references can be used to assess growth of BF infants who were
      fed according to Thai guidelines of infant feeding. DESIGN: Cohort study.
      MATERIAL AND METHOD: One hundred and fifty six term infants (78 BF and 78 FF
      infants) were followed prospectively for 12 months. Milk was the only food source
      during the first 4 months and solid foods were introduced after 4 months of age.
      Body weight, length and head circumference were measured at the age of 1, 2, 4,
      6, 9 and 12 months. RESULTS: Of the 156 infants, 140 completed the study (71 BF
      and 69 FF infants). BF and FF infants had similar mean weight and length from 0
      to 6 months, thereafter BF infants had lower weight and length than FF infants
      with significant difference at 9-12 months in male infants and at 12 months in
      female infants (p < 0.05). Compared with national growth references of Thai
      children, mean weight and length of BF and FF infants in the study were
      significantly lower than the mean values of Thai infants from 0 to 1 months,
      thereafter mean weight and length of BF infants were close to the Thai references
      but those of FF infants were higher than the Thai references after 6 months with
      significant difference in weight from 9 to 12 months and length at 12 months. The
      incidence of malnutrition and obesity at 1 year of age was not different between
      the two feeding groups. Inadequate complementary food was the risk factor of
      infant malnutrition (adjusted RR 4.7, 95% CI 1.1-21.9, p 0.04). CONCLUSION: BF
      and FF infants had similar weight and length from birth to 6 months, thereafter,
      FF infants had higher weight and length than BF infants and Thai growth
      references. Growth of BF infants correlated well with the national growth
      references of Thai children, so the Thai growth references can be used to assess
      growth of BF infants who were fed according to Thai guidelines of infant feeding.

PMID- 15962667
TI  - Screening for diabetic retinopathy in rural area using single-field, digital
      fundus images.
AB  - OBJECTIVE: To evaluate the practicability of using single-field, 2.3 million
      pixel, digital fundus images for screening of diabetic retinopathy in rural
      areas. MATERIAL AND METHOD: All diabetic patients who regularly attended the
      diabetic clinic at Kabcheang Community Hospital, located at 15 kilometers from
      the Thailand-Cambodia border, were appointed to the hospital for a 3-day diabetic
      retinopathy screening programme. The fundi of all patients were captured in
      single-field, 45 degrees, 2.3 million-pixel images using nonmydriatic digital
      fundus camera and then sent to a reading center in Bangkok. The fundi were also
      examined through dilated pupils by a retinal specialist at this hospital. The
      grading of diabetic retinopathy from two methods was compared for an exact
      agreement. RESULTS: The average duration of single digital fundus image capture
      was 2 minutes. The average file size of each image was 750 kilobytes. The average
      duration of single image transmission to a reading center in Bangkok via
      satellite was 3 minutes; via a conventional telephone line was 8 minutes. Of all
      150 patients, 130 were assessed for an agreement between dilated fundus
      examination and digital fundus images in diagnosis of diabetic retinopathy. The
      exact agreement was 0.87, the weighted kappa statistics was 0.74. The sensitivity
      of digital fundus images in detecting diabetic retinopathy was 80%, the
      specificity was 96%. For diabetic macular edema the exact agreement was 0.97, the
      weighted kappa was 0.43, the sensitivity was 43%, and the specificity was 100%.
      CONCLUSION: The image capture of the nonmydriatic digital fundus camera is
      suitable for screening of diabetic retinopathy and single-field digital fundus
      images are potentially acceptable tools for the screening. The real-time image
      transmission via telephone lines to remote reading center, however, may not be
      practical for routine diabetic retinopathy screening in rural areas.

PMID- 15962668
TI  - Long-term treatment of N-3 PUFAS on plasma lipoprotein levels and fatty acid
      composition of total serum and erythrocyte lipids in hypertriglyceridemic
      patients.
AB  - The low incidence of coronary heart disease in Greenland Eskimos and Japanese
      fishermen who have high consumption of fish and seafood has called the attention
      in the role of eicosapentaenoic (EPA = 20:5n-3) and docosahexaenoic (DHA = 22: 6n
      3) acids, the major n-3 polyunsaturated fatty acids (PUFAs) in fish oils, in
      reducing cardiovascular risk. N-3 PUFAs may reduce serum lipids by promoting
      fatty acid oxidation and decrease VLDL producing from the liver, depress tissue
      arachidonate synthesis and alter the composition and tissue PUFAs. Plasma
      lipoprotein and fatty acid composition of total serum and erythrocyte lipids in 9
      hypertriglyceridemic patients consisting of 4 males and 5 females aged 39-72 yr
      who attended the Nutrition Clinic, Ramathibodi Hospital were investigated. The
      study period consisted of 4 wks of dietary advice only followed by 48 wks of
      dietary advice with a daily intake of 6 g of fish oil capsules (FOC). Six grams
      of FOC provided 1080 mg of 2:5n-3 and 720 mg of 22:6n-3. Their plasma
      triglyceride (TG) levels at wk 0, 12, 24, 36, 48 were 356.7, 230.1, 209.7, 192.9,
      22 7.4 mg/dL and M-particle (equivalent to very low density lipoprotein, VLDL)
      were 484.4, 354.8, 383.1, 349.7, 453.2 mg/dL respectively that decreased
      significantly, whereas their plasma low density lipoprotein cholesterol (LDL-C)
      levels at the same periods were 139.4, 164.9, 171.0, 157.1, 158.3 mg/dL that
      increased significantly. Serum and erythrocyte 20:5n-3 and 22:6n-3 in these
      subjects were significantly higher than those at wk 0 throughout the study. These
      findings indicate the bioavailability of 20: 5n-3 and 22:6n-3 in TG lowering
      effect of FOC. Fatty acids from fish oil have a remarkable effect on the
      synthesis and clearance of TG-rich lipoproteins, especially VLDL and
      chylomicrons. Though daily treatment with 6 g of FOC has a striking effect in
      increasing plasma LDL-C levels.

PMID- 15962669
TI  - Accuracy of transcutaneous bilirubinometer estimates using BiliCheck in Thai
      neonates.
AB  - BACKGROUND: Neonatal jaundice is the most frequently encountered diagnostic and
      therapeutic problem in the newborn. In the jaundiced infant, it is thought that
      the binding capacity of plasma albumin is exceeded, which allows free bilirubin
      to diffuse into and accumulate within extravascular tissues, such as the central
      nervous system. Affected newborns may develop kernicterus. The standard method of
      serum bilirubin measurement requires blood specimen taken by heel prick or
      venepunetue which involves pain of the newborn and is time consuming. A non
      invasive, transcutaneous measurement of bilirubin concentration is developed to
      be an alternative method as a reliable for the screening method to detect
      hyperbilirubinemia OBJECTIVE: To compare the estimates of serum bilirubin using a
      recently introduced device called a BiliCheck and its transcutaneous
      bilirubinometer index with the standard direct spectrophotometric measurement of
      serum bilirubin. DESIGN: Prospective descriptive study. MATERIAL AND METHOD:
      Estimates of serum bilirubin, as measured using the BiliCheck, were compared with
      serum bilirubin concentration measured by direct spectrophotometry in neonates at
      Songklanagarind Hospital. Transcutaneous bilirubinometer readings were taken on
      the forehead. RESULTS: Eighty-two newborns were enrolled in the present study.
      The means and standard deviations of serum bilirubin concentration and
      transcutaneous bilirubinometer index were 11.96 +/- 2.98 and 11.61 +/- 2.93
      mg/dl, respectively. There was no statistically significant difference (p = 0.44,
      paired t-test). The correlation coefficient between total serum bilirubin and
      BiliCheck index was 0.95 with the linear regression equation of Y= 0.99x + 0.4.
      CONCLUSION: Serum bilirubin can be accurately measured by the transcutaneous
      bilirubinometer index in full term newborn infants prior to any intervention
      modalities.

PMID- 15962670
TI  - A germline mutation in a Thai family with familial multiple endocrine neoplasia
      type 1.
AB  - Multiple endocrine neoplasia type 1, caused by the mutation in the MEN1 gene, is
      an autosomal dominant disorder with over 95% penetrance characterized by
      hyperparathyroidism, pancreatic endocrine tumor and pituitary tumor. The authors
      performed a molecular analysis to identify a mutation in a Thai man with MEN1. He
      was found to be heterozygous for IVS6 + 1G to A. Two of his three children were
      also found to carry this mutation. The newly available genetic test for patients
      with MEN1 in Thailand makes it possible to accurately DNA-based diagnose
      clinically suspected individuals and their presymptomatic members, which has
      important therapeutic impacts on them.

PMID- 15962671
TI  - Prevalence of cardiovascular risk factors in a rural area in Southern Thailand:
      potential ethnic differences.
AB  - In Thepa district, Songkhla province, Southern Thailand, parents of children
      being followed long term from conception for their development (N 1325), as well
      as health workers of the same district (N 150) were surveyed with regards to
      anthropometry, occupation, family size, food and leisure habits, and blood levels
      of lipids, sugar, creatinine and hematocrit. Differences among those of Thai or
      Chinese extracts (Thai-Buddhists) and those of Malay extracts (Thai-Muslims) were
      separately evaluated for males and females. The mean age for the group (N 1475,
      including 636 couples) was 31.5 +/- 7.3 (SD) and ranged from 15-66 years. There
      were 794 females (485 Muslims) ages 29.6 +/- 6.6 (SD). The Muslim families were
      larger in size averaging 2.8 +/- 1.6 children while the Buddhist's averaged 1.9
      +/- 0.9. Fifty four percent of the group were engaged in rubber tapping and this
      often included both members of the family. Sixty eight percent of the males
      currently smoked Differences in measured variables between Muslims and Buddhists
      were minimal. The most striking however was the high density lipoprotein
      cholesterol (HDL-C) among the males where the age-adjusted average was 51.3 +/-
      0.72 (SE) among the Buddhists and 42.2 +/- 0.59 (SE) in the Muslims. This
      difference was significant even when adjusted for other related variables.
      Differences in the ethnic groups were also examined in terms of prevalence of
      risks (hypertension, BMI > or = 25%, waist-hip-ratio, fasting plasma glucose > or
      = 110 mg%, total cholesterol > or = 200 mg%, triglyceride > or = 150 mg% and low
      HDL-C). For hypertension (systolic > or = 140 or diastolic > or = 90 mmHg),
      female Muslims showed higher prevalence (4.5% vs 1.6%; OR 2.82 CI 1.04-7.64). For
      low HDL-C, male Muslim showed higher prevalence 23.6 vs 8.8%, OR 2.31 CI 1.27
      4.22). Other risks showed no differences among the ethnic groups. The differences
      in parameters or in prevalence of risk between these two ethnic groups (minimal
      intermarriage) are distinct from differences among Malays and Chinese in
      Singapore where such differences were subsequently reflected in the differences
      in incidence and out-come of ischemic heart diseases.

PMID- 15962672
TI  - Plasma ascorbate and ceruloplasmin levels in Thai premature infants.
AB  - BACKGROUND: Free radicals have been implicated in the pathogenesis of some
      complications among premature infants. Even though ascorbate is an important anti
      oxidant in human plasma, it can also act as a pro-oxidant at high concentrations
      in the presence of metal ions, which causes oxidative damage in premature
      infants. OBJECTIVE: To determine plasma ascorbate and ceruloplasmin levels in
      premature infants (and their mothers) and full-term infants and to compare
      between groups. MATERIAL AND METHOD: Premature (n = 27) and full-term infants (n
      = 24) and the mothers of the premature infants (n = 13) admitted to Srinagarind
      Hospital, Khon Kaen University, Thailand, were enrolled in the study. Plasma
      ascorbate and ceruloplasmin levels were determined and compared among various
      clinical presentations. RESULTS: Plasma ascorbate has negative correlation with
      gestational age of infants. Its level on day 1 of the premature infants was
      significantly higher than full-term group (52.62 vs 39.00 micromol/L) and then
      decline after birth. Premature infants receiving oxygen therapy had lower plasma
      ascorbate than premature infants without oxygen therapy (p = 0.017). Plasma
      ascorbate in premature infants who died was higher than in those that survived (p
      = 0.029). Premature infants with poor outcomes had a higher ratio of plasma
      ascorbate to ceruloplasmin than those with good outcomes (p < 0.05). CONCLUSION:
      This study shows that high plasma ascorbate and low ceruloplasmin levels are
      associated with poor outcomes of premature infants; that is, ascorbate can act as
      either an anti-oxidant or a pro-oxidant.

PMID- 15962673
TI  - Early experience with pediatric cardiac intervention in Songklanagarind Hospital.
AB  - BACKGROUND: Nowadays, pediatric cardiac intervention is an effective optional
      treatment for congenital heart disease (CHD). Several cardiac centers have been
      established in different regions of Thailand and Songklanagarind Hospital is the
      newest of these university cardiac centers. OBJECTIVE: To report results and
      complications of transcatheter treatment for congenital cardiac defects in
      Songklanagarind Hospital. MATERIAL AND METHOD: The medical database was reviewed
      for the results and complications of different types of pediatric cardiac
      intervention from May, 2000 to December, 2003. RESULTS: There were 102 cases of
      pediatric cardiac intervention. Sixty-seven were patent ductus arteriosus (PDA),
      16 were valvular pulmonary stenosis (VPS), 10 were cyanotic CHD which needed
      balloon atrial septostomy (BAS), 8 were abnormal aorto-pulmonary (AP)
      collaterals, and 1 was severe valvular aortic stenosis (VAS). Coil embolization
      was performed in 53 patients with PDA and 8 patients with AP-collateral vessels,
      32 of PDAs (60.4%) and all AP-collateral vessels (100%) were completely
      obliterated within 24 hours. The Amplatzer duct occluder (ADO) was deployed in 14
      PDAs with 100% completely obliteration within 24 hours. In those with VPS or VAS,
      percutaneous balloon valvuloplasty (PBV) was the treatment of choice. The mean
      peak to peak systolic pressure gradient in VPS was reduced from 62.8 +/- 33.3
      mmHg to 33.33 +/- 33.33 mmHg and from 76 mmHg to 49 mmHg in VAS after the
      procedures. In BAS, the mean diameter of atrial communication increased from 3.0
      +/- 0.7 mm to 5.9 +/- 0.4 mm. In coil embolization, 8 had distal PA embolization
      (15%), 1 had hemolysis (2%) and 1 had decreased dorsalis pedis pulse (2%). One
      (7%) of the ADO-implanted patients had a weak femoral pulse. Of the VPS cases, 1
      died from intractable heart failure, and 1 developed hemiparesis, from which they
      completely recovered within 6 months. The patient with VAS had a femoral artery
      complication. CONCLUSION: Pediatric cardiac intervention in Songklanagarind
      Hospital has satisfactory results with an acceptable complication rate.

PMID- 15962674
TI  - Relationship between soluble leptin receptor, leptin, lipid profiles and
      anthropometric parameters in overweight and obese Thai subjects.
AB  - Median, range and 95% confidence interval (CI) for median of age, anthropometric
      variables, soluble leptin receptor, serum leptin and lipid profile levels of 48
      overweight (Body mass index (BMI) = 25.00-29.99 kg/m2) and obese (BMI > or = 30.
      00 kg/m2) Thai males and 166 overweight and obese Thai females, compared with 26
      males and 81 females in a control group (BMI = 18.50-24.99 kg/m2), were
      determined The study subjects were persons who turned up regularly for physical
      check-ups at the Out-patient Department, General Practice Section, Ratchawithi
      Hospital, Bangkok, aged between 18-60 years. Serum leptin, triglyceride and low
      density lipoprotein cholesterol/high density lipoprotein cholesterol ratios (LDL
      C/ HDL-C ratio) were significantly higher in the overweight and obese males and
      females. Soluble leptin receptor and HDL-C were significantly lower in the
      overweight and obese males and females. Cholesterol and LDL-C were significantly
      higher in the overweight and obese females, but there was no significant
      difference in the overweight and obese males when compared with the control
      males. Low soluble leptin receptor levels were found in 38.1% (8/21) of the
      overweight and obese males, while 31.5% (29/92) were found in the overweight and
      obese females. Elevated leptin levels were found in 66.7% (32/48) and 89.8%
      (149/166) of the overweight and obese males and females, respectively. Both low
      soluble leptin receptor levels and elevated leptin levels were found in 9.5%
      (2/21) and 29.4% (27/92) of the overweight and obese males and females,
      respectively. A significant positive correlation was found between soluble leptin
      receptor and cholesterol, and between weight, BMI, waist, hip and HDL-C, with
      leptin. Serum soluble leptin receptor levels were significantly negatively
      correlated with leptin and BMI. The results can elucidate the causes and
      consequences of obesity, and are expected to aid the provision of care for
      overweight and obese Thai people.

PMID- 15962675
TI  - Detection of cytomegalovirus in vitreous, aqueous and conjunctiva by polymerase
      chain reaction (PCR).
AB  - OBJECTIVE: To evaluate the diagnostic value of polymerase chain reaction (PCR)
      performed on vitreous, aqueous and conjunctiva for the detection of
      cytomegalovirus in AIDS patients with a clinical diagnosis of cytomegalovirus
      retinitis. MATERIAL AND METHOD: PCR-based assay was used to detect
      cytomegalovirus DNA in vitreous, aqueous and conjunctival samples from 24
      patients with the acquired immunodeficiency syndrome (AIDS) who had untreated
      clinically diagnosed cytomegalovirus retinitis and from 15 immunocompetent
      patients, including 11 with retinal detachment, 2 with macular hole and 2 with
      vitreous hemorrhage. RESULTS: Cytomegalovirus DNA was detected in 16, 9 and 3 of
      24 vitreous, aqueous and conjunctival samples, respectively, from patients with
      AIDS, untreated clinically diagnosis of cytomegalovirus retinitis; and in one
      patient out of 15 vitreous, aqueous and conjunctival samples from immunocompetent
      patients with vitreoretinal diseases. CONCLUSION: The use of PCR in the detection
      of cytomegalovirus in vitreous, aqueous and conjunctival samples had an equal
      specificity of 93% and had sensitivity of 67, 37 and 12%, respectively.

PMID- 15962676
TI  - Efficacy of benzimidazole carbamate on an intestinal fluke co-infected with
      nematodes.
AB  - The efficacy of a single dose of benzimidazole, drugs commonly used for the
      treatment of Ascaris and hookworm, was evaluated against one of the tiny-sized
      intestinal flukes, Haplorchis sp in the endemic area where mixed infections of
      roundworms and flatworms existed. At day 7 after treatment, albendazole (400 mg)
      induced 42.5% cure rate, mebendazole (500 mg) a cure rate of 32.4%, on the other
      hand, praziquantel (40 mg/kg) gave 94.6% cure rate and the placebo at 15.9%. At
      the single dose, benzimidazole could not completely expelled the haplorchid; but
      could reduce one third to two fifth of the infection, similar to the drugs
      efficacy against Trichuris infection.

PMID- 15962677
TI  - Experience on endoscopic retrograde cholangiopancreatography at tertiary referral
      center in Thailand: risks and complications.
AB  - BACKGROUND: Several complications from ERCP have been described, including
      pancreatitis, hemorrhage, perforation, and cholangitis. The actual incidences and
      risk factors in Thailand have never been analyzed. MATERIAL AND METHOD: The
      authors retrospectively reviewed the outcome of ERCP at Chulalongkorn University
      Hospital between September 2000 and December 2002. Potential risk factors were
      statistically assessed. RESULTS: The incidence of post-ERCP pancreatitis,
      hemorrhage, perforation and cholangitis was 3.6%, 2.1%, 1.2% and 6%,
      respectively. Risk factors of pancreatitis were the suspected diagnosis of
      sphincter of Oddi dysfunction and pancreatic interventions, especially through
      minor papilla. Prophylactic pancreatic duct stent prior to precut sphincterotomy
      may reduce the incidence of pancreatitis. Hemorrhage was associated with duodenal
      diverticulum. The incidence of cholangitis was higher in biliary duct dilation
      and cholangiocarcinoma, especially hilar involvement. CONCLUSION: Incidence of
      these complications was comparable to international series with similar risk
      factors. Cholangitis developed more frequently probably due to a higher incidence
      of cholangiocarcinoma.

PMID- 15962678
TI  - Does preloading with colloids prevent hemodynamic changes when neurosurgical
      patients are subsequently changed to the seated position?
AB  - OBJECTIVE: This prospective, randomized, double-blind study was designed to
      determine and compare the usefulness of preloading colloids (Haemaccel) 10 ml/Kg
      before positioning whether it can prevent hemodynamic changes during seated
      positioning or not. MATERIAL AND METHOD: The authors studied 20 patients by
      randomly dividing them into 2 groups. The control group was given crystalloid as
      maintenance and deposit replacement but the study group was given extra colloids
      10 ml/Kg 30 minutes before starting general anesthesia. Both groups were
      monitored and given anesthesia, balanced technique. Systolic and diastolic blood
      pressures, heart rate, central venous pressure (CVP) at different time intervals
      in the sitting position for 30 minutes were recorded. Statistical analysis was
      done by Student t-test, Chi-square test and ANOVA (p-value < 0. 05 considered
      significant). RESULTS: The results showed that systolic blood pressure at 15, 20,
      30 minutes and CVP at 15, 25, 30 minutes after positioning in the study group was
      maintained significantly compared to the control group and there were no
      significant changes in diastolic blood pressure and heart rate. There were no
      other complications during the sitting period. CONCLUSION: It is concluded that
      preloading colloid fluid prior to repositioning could prevent the decrease of
      systolic blood pressure and central venous pressure during sitting positioning
      without other complications.

PMID- 15962679
TI  - Radiation scattering to the primary surgeon during closed locked femoral nailing.
AB  - A prospective study of the radiation exposure to the primary surgeon during
      closed static locked femoral nailing was performed in 50 cases. There were 44
      males and 6 females whose ages ranged from 15 to 70 years (average, 32). The
      degree of fracture comminution was classified by Winquist. The cases included 1
      Winquist (WQ)1, 9 WQ2, 27 WQ3 and 13 WQ4. The Grosse-Kempf femoral nail was used
      in 40 cases and the AO interlocking femoral nail was used in 10 cases. The C-arm
      image intensifier model Phillip BV212 and BV 300 were used during the present
      study. The average operation time was 52 minutes (range, 30 to 120). The
      fluoroscopic time for the entire procedure average 132 seconds (range, 23 to
      366). The radiation exposure to the primary surgeon ranged from 2 to 231 micro-Sv
      with an average of 30 micro-Sv per procedure. From the present study, it was
      found that radiation scattered to the primary surgeon during current practice for
      closed static femoral nailing using the recent model of C-arm image intensifier
      was minimal and far below the permissible dose. It was also found that the group
      using the C-arm model BV 300 (n = 16) had significant lesser fluoroscopic time
      and less radiation scattering to the primary surgeon than the group with model BV
      212 (n = 34).

PMID- 15962680
TI  - The efficacy and effectiveness of influenza vaccination among Thai elderly
      persons living in the community.
AB  - OBJECTIVE: To determine the efficacy and cost-effectiveness of influenza
      vaccination in the Thai elderly living in an urban community. MATERIAL AND
      METHOD: The study design was a stratified, randomized, double blind, placebo
      controlled trial. A total of 635 participants aged 60 years and older living in
      an urban community was randomized to receive an influenza vaccine or tetanus
      toxoid as a placebo injection. All participants were followed up 4-6 weeks in the
      community for influenza-like illness and treatment received, hospitalization and
      death for one year. A hemagglutination inhibition (HI) test for influenza virus
      antibody of all participants was done on the day of vaccination as well as 1
      month, 5 months, and 12 months after the vaccination. Main outcome measures were
      immune response rate and protective titer, influenza-like illness, serological
      influenza, treatment received for influenza-like illness and their expenses,
      hospitalization and death during the study period. RESULTS: The immune response
      rate of vaccinations was 97.1% and protective titer for A (H1N1) and A (H3N2)
      strains were 96.4 and 98.6%, respectively. The incidence of influenza-like
      illness was 4.83% in the vaccine group compared with 10.88% in the placebo group.
      The relative risk reduction was 56% (95% CI = 14 to 77%). The survival analysis
      also showed that vaccinations significantly reduced the incidence of influenza (p
      = 0. 009). The number needed to prevent one episode was 17 persons (95% CI = 9 to
      71 persons). The adverse reactions of vaccinations were mild and tolerable.
      However, the number of treatments received for influenza-like illness and their
      cost were not significantly different between the two groups. None of the
      subjects had pneumonia nor needed hospitalization during the study period. Seven
      participants died during the year of follow up, but not from influenza.
      CONCLUSION: In Thai elderly living in the community, influenza vaccination
      reduced the incidence of influenza-like illness by half, but not the number of
      treatments received for influenza-like illness, their cost, and its serious
      complications. In the year of the study, considering the cost of vaccines and the
      numbers needed to prevent one episode of infection from the provider's viewpoint,
      it may not be cost-effective to recommend that all Thai older persons living in
      the community should receive influenza vaccination annually. Vaccination
      recommendation for the elderly should be promptly implemented in expectation of a
      severe epidemic in Thailand.

PMID- 15962681
TI  - Lumbo-peritoneal shunting improved spinal cord compression due to a large
      anterior sacral meningocele.
AB  - OBJECTIVE: Lumbo-peritoneal shunt was used as an alternative treatment in a large
      anterior sacral meningocele, a rare congenital malformation, is illustrated.
      CLINICAL PRESENTATION: A 48-year-old female patient presented with a two-month
      history of progressive paraparesis, leg pain and numbness of both legs. The
      investigation demonstrated spina bifida with a huge sac of meningocele,
      protruding anteriorly into the pelvic cavity. On two previous surgical operations
      for closure, the fistula through the posterior transsacral approach failed 20
      years ago at another hospital, but her symptoms had subsided spontaneously
      without explanation. She came to Thammmasat Hospital with an episode of spinal
      cord compression for 2 months. MANAGEMENT: Because of the old surgical scar and
      high pressure of the meningocele, a lumbo-peritoneal shunt was selected to drain
      the cerebrospinal fluid from the meningocele to the peritoneal cavity.
      CONCLUSION: Lumbo-peritoneal shunting is an optional treatment for a large sacral
      meningocele, especially in a large fistula with unsuccessful surgical closure.

PMID- 15962683
TI  - Waiver of consent in clinical observational research.
AB  - In the present article the requirements for waivers of informed consent in
      clinical research on subjects who are patients in a hospital are reviewed The
      most important requirements seem to be that the research must pose minimal risk
      and obtaining informed consent is impracticable. It is suggested that
      requirements for waivers of consent in research ethics guidelines be modified to
      exclude the requirement of impracticable consent, but to retain that of minimal
      risk research, and to add another requirement that restricts modifications of the
      medical management procedures to those which are minor in some sense. According
      to these suggestions, waivers of consent for retrospective chart reviews are seen
      to be coherent and consistent. These suggestions also imply that certain types of
      prospective observational studies should also be granted waivers of consent. On
      the other hand, waivers of consent should probably not be granted to any type of
      randomized clinical trials.

PMID- 15962682
TI  - Balloon expandable stents for coarctation of the aorta: current status and
      technical considerations: case report.
AB  - BACKGROUND: Balloon expandable stents have been used to manage coarctation of the
      aorta (Co) in selected patients with very encouraging results. MATERIAL AND
      METHOD: The authors report here the first group of patients with Co who underwent
      a successful implantation of the new Palmaz Genesis stent with intermediate term
      follow up. RESULTS: There were 5 patients with an age range from 14 to 23 years
      old. All of them had significant Co and were receiving multiple anti-hypertensive
      medications. Primary stenting was performed in all patients. All of them had an
      immediate relief of the gradient. All antihypertensive medications were
      discontinued immediately in 4 patients. All patients had one year follow up which
      revealed a minimum gradient. One patient continues to receive oral
      antihypertensive medication. CONCLUSION: In patients with coarctation of the
      aorta (native or recoarctation of aorta), stent implantation may be a feasible
      and improved option to relieve the stenosis. Short and mid term followup of these
      patients have shown encouraging results.

PMID- 15962684
TI  - Laboratory diagnosis of rabies in Bangkok and the central part of Thailand, 2001
      2004.

PMID- 15962685
TI  - Animals and ethics.

PMID- 15962686
TI  - Visuospatial abilities, memory, and executive functioning in trichotillomania and
      obsessive-compulsive disorder.
AB  - Few studies have compared neuropsychological functioning in trichotillomania
      (TTM) and obsessive-compulsive disorder (OCD). In OCD, most studies suggest
      abnormal visuospatial abilities, memory, and executive functioning. We compared
      23 TTM, 21 OCD and 26 healthy control individuals on neuropsychological tasks
      assessing these abilities. Neither the TTM nor the OCD groups suffered from
      generalized neuropsychological deficits compared to the healthy control group.
      TTM participants showed increased perseveration on the Object Alternation Task
      suggesting difficulties with response flexibility. OCD participants showed
      impaired ability to learn from feedback on the Wisconsin Card Sorting Test. Other
      executive functions, as well as memory and visuospatial abilities were unimpaired
      in TTM and OCD. Our data suggest that TTM and OCD are characterized by different
      patterns of neuropsychological dysfunction.

PMID- 15962687
TI  - Dichotic target detection with words: a modified procedure.
AB  - The purpose of the present study was to investigate the influence of attention on
      the magnitude and reliability of laterality effects in dichotic target detection.
      Twenty-five participants completed a dichotic target detection task requiring
      them to identify the ear to which a target word was presented. Correct left and
      right responses (LL and RR outcomes, respectively) produced a large and reliable
      right ear advantage (REA). Participants circled right when the target was
      presented to the left ear (LR outcomes) more often than they circled left when
      the target was presented to the right (RL outcomes). A combination of the LL+LR
      outcomes compared to RR+RL outcomes resulted in a reduced REA. Finally, cases
      where participants incorrectly responded left or right when the target was absent
      produced no systematic differences, reflecting the absence of a generalized bias
      to respond "right." The discussion emphasizes the usefulness of the approach
      presented here in producing a score that minimizes the attentional component of
      laterality effects.

PMID- 15962688
TI  - Ecological validity of the WMS-III rarely missed index in personal injury
      litigation.
AB  - The purpose of this study was to evaluate the clinical utility of the Rarely
      Missed Index (RMI) to detect cognitive exaggeration in 78 nonlitigant patients
      (i.e., Mixed Clinical group) and 158 personal injury litigants (i.e., 20
      Suspected Exaggerators, 12 Borderline Exaggerators, 126 Genuine Responders). The
      base rate for probable malingered neurocognitive dysfunction in the litigant
      sample was 12.7%. The false positive error rate of the RMI in the Genuine
      Responder and Mixed Clinical group ranged from 5.4% to 8.6%. Positive RMI scores
      were found in 25% and 41.7% of the Suspected Exaggerator and Borderline
      Exaggerator groups respectively. The clinical utility of the RMI to identify
      Suspected Exaggerators versus individuals in the Genuine Responder and Mixed
      Clinical groups revealed low sensitivity (sensitivity = .25), very high
      specificity (range = .91 to .95), moderate positive predictive power (range = .50
      to .71), and moderate to high negative predictive power (range = .68 to .83).
      These results do not support the use of the RMI as a reliable predictor of
      cognitive exaggeration.

PMID- 15962689
TI  - Visual memory testing in older adults with age-related visual decline: a measure
      of memory performance or visual functioning?
AB  - Although we know that vision is correlated with memory performance in older
      adults, the implications for this in terms of neuropsychological assessment have
      not been investigated. Relationships among age, visual acuity, and visual and
      verbal memory in 89 community dwelling volunteers aged 60 to 87 years were
      examined. Vision was tested using the Landolt C and visual and verbal memory were
      assessed via the Visual Reproduction (VR) and Word List (WL) subtests from the
      Wechsler Memory Scale, Third Edition (WMS-III; Wechsler, 1997), respectively.
      Significant correlations were observed between vision and the VR and WL tasks.
      Hierarchical multiple regression analyses revealed that vision significantly
      increased the R2 for VR and WL after controlling for age and education. The
      effect of vision was not specific to visual memory. We conclude that vision is
      correlated with general memory function in older adults, and is not modality
      specific.

PMID- 15962690
TI  - Specific impairments of selective attention in mild Alzheimer's disease.
AB  - The aim of the present study was to evaluate selective visual attention in
      subjects affected by Alzheimer's Disease (AD), by means of a computerized spatial
      exploration test that adopts a Touch Screen (TS) interface, which has already
      proved able to characterize alternative strategies in performing search tasks. We
      assessed a group of 16 patients affected by mild to moderate AD, comparing them
      with 16 control subjects matched for age and education. In the experimental tasks
      the performance of the AD patients was worse than that of the normal elderly,
      both quantitatively (slower speeds) and qualitatively (poorer planning and higher
      number of omissions and perseverations). In the visual attention tasks there
      appeared to be no close connection between AD patients' performance and increased
      Reaction Times (RT); this evidenced a specific role of non-elementary cognitive
      structures enclosed in a higher attentional domain, rather than a general
      decrease in the speed of basic cognitive processes. Our results are in line with
      specific AD literature: while psychomotor speed and lower attention levels
      (sensorimotor) are preferentially impaired in subcortical forms of dementia, the
      higher levels of selective and divided attention could be the first to
      deteriorate and appear more markedly disrupted in the Alzheimer type of dementia.

PMID- 15962691
TI  - Development and Validation of the Design Organization Test (DOT): a rapid
      screening instrument for assessing visuospatial ability.
AB  - A brief paper-and-pencil instrument was developed to rapidly assess visuospatial
      ability and serve as an alterative to the WAIS Block Design subtests during
      screening or when assessment time is limited. The Design Organization Test (DOT)
      consists of square black-and-white grids with visual patterns similar to those of
      the Block Design subtests. Administration is straightforward and requires
      examinees to reproduce as many designs as possible in 2 minutes using a numerical
      code key. For 411 college students, alternate forms of the DOT yielded
      reliability estimates comparable to that of the test-retest reliability of WAIS
      III Block Design subtest. In a clinical sample, the DOT was significantly
      correlated (r = .92) with WAIS-III Block Design scores and was successfully
      substituted in place of Block Design raw scores without significant change in
      Performance IQ or Full Scale IQ. The results suggest that the DOT provides a
      useful and rapid screening measure of visuospatial ability.

PMID- 15962692
TI  - Contraversive pushing and inattention of the contralesional hemispace.
AB  - The aim of this study was to investigate, in 114 stroke patients, the frequency
      of occurrence of a largely unknown neurological disorder, characterized by a
      postural imbalance due to a 'pushing away' reaction of the body towards the
      contralesional side of space, in function of hemispheric lesion localization and
      gender. The study also investigate the relation of this contraversive pushing
      with active movement, somatosensory perception deficits and, in particular,
      inattention of contralesional hemispace and body. The similarity of the presence
      of contraversive pushing and the syndrome of spatial hemineglect together with a
      gender-related differentiation suggest the existence of a "pusher syndrome", in
      which the pathophysiology points in the direction of a spatial higher-order
      processing deficit, related to spatial inattention, underlying the higher
      frequency and severity of contraversive pushing after right brain lesions.

PMID- 15962693
TI  - Attentional inhibition in patients with focal frontal lobe lesions.
AB  - Patients with unilateral, frontal lobe damage and matched controls performed an
      identity negative priming task as a measure of inhibition in selective attention.
      Control participants demonstrated a normal negative priming effect, as evidenced
      by slower reaction times when a previously to-be-ignored item became the target
      on a subsequent trial (distractor suppression). On the other hand, patients with
      left medial frontal lobe damage showed positive priming in the distractor
      suppression condition suggesting facilitation of distractor information. Patients
      with right frontal lobe damage showed an unreliable pattern of negative priming,
      some demonstrating an absence of negative priming and others demonstrating
      enhanced negative priming in the distractor suppression condition. Neither
      patient group nor controls demonstrated slower responses on a target-to
      distractor condition included to evaluate a noninhibitory (i.e., episodic
      retrieval) account of negative priming. Taken together, our results suggest that
      (a) the negative priming effect represents active inhibition of a distractor
      representation, rather than a noninhibitory mismatch between retrieval episodes,
      and (b) that the frontal lobes, especially the left frontal lobes, contribute to
      this active inhibition.

PMID- 15962694
TI  - Learning and memory in aging combat veterans with PTSD.
AB  - The California Verbal Learning Test (CVLT) was administered to examine learning
      and memory performance in aging combat veterans with (n = 30) and without PTSD (n
      = 20), and veterans unexposed to combat (n = 15). Combat veterans with PTSD
      (PTSD+) showed many impairments compared to non-exposed veterans, but only long
      delay free recall consistently discriminated the PTSD+ group from combat-exposed
      subjects without PTSD (PTSD-), when data were corrected for subscale scores on
      the WAIS (Vocabulary, Block Design). Alterations in total learning were
      associated with PTSD when controlling for substance abuse and depression. Two
      contrast measures, proactive interference and recognition hits, distinguished
      combat from noncombat veterans, and may be related to trauma exposure.
      Impairments in total learning are similar to what has been observed in Holocaust
      survivors. However, increased severity of rapid forgetting may be a specific
      alteration in older combat veterans, likely reflecting aspects of both combat
      exposure and aging.

PMID- 15962695
TI  - Recognition memory in Parkinson's disease with and without dementia: evidence
      inconsistent with the retrieval deficit hypothesis.
AB  - Parkinson's disease (PD) has been associated with a pattern of performance on
      memory tests in which free recall is impaired but recognition and cued recall are
      intact, indicating problems with memory retrieval. Recent findings suggest that
      PD patients exhibit deficits in recognition as well as free recall, however. The
      current study set out to provide clear evidence that recognition and cued recall
      are not intact in PD. Ninety-nine idiopathic PD patients were administered the
      California Verbal Learning Test and their performance was compared to a well
      matched normative sample. A profile analysis revealed that nondemented patients
      exhibited deficits on measures of cued recall and delayed recognition that were
      similar in magnitude to that of free recall. This was also the case for the cued
      recall deficits exhibited by demented patients; however, in this group
      recognition was worse than free recall. In both groups poor recognition appeared
      due to an elevated number of false positive errors. These results are
      inconsistent with the retrieval deficit hypothesis but support the notion that PD
      memory problems are secondary to prefrontal dysfunction.

PMID- 15962696
TI  - Reliability and validity of the fine motor scale of the Peabody Developmental
      Motor Scales-2.
AB  - This study examined the test-retest reliability, inter-rater reliability,
      convergent validity and discriminant validity of the Fine Motor Scale of the
      Peabody Developmental Motor Scales-second edition (PDMS-FM-2). Participants
      included two groups of 18 children between the ages of 4 and 5 years with and
      without mild fine motor problems. The PDMS-FM-2 was administered twice to 12
      children and rated by two occupational therapists. The PDMS-FM-2 results were
      compared with scores on the Movement Assessment Battery for Children (M-ABC). In
      addition, the scores of the children with and without fine motor problems were
      compared. For the test-retest reliability and the inter-rater reliability,
      correlation coefficients varied from r = 0.84 to r = 0.99. These results suggest
      that PDMS-FM-2 has excellent test-retest and inter-rater reliability. Convergent
      validity with the fine motor section of the M-ABC and discriminant validity have
      been confirmed. Only 39% of the children in the group with problems in fine motor
      activities had fine motor problems according to the PDMS-FM-2. This finding seems
      to indicate that the PDMS-FM-2 may not be sensitive enough for this population.

PMID- 15962697
TI  - Effects of a hand training programme in five patients with myotonic dystrophy
      type 1.
AB  - The aim of this study was to evaluate hand function and self-rated occupational
      performance before and after specific hand training in five participants with
      myotonic dystrophy (MD) type 1. MD is the commonest of the muscular dystrophies
      with adult onset and is associated with muscle weakness, wasting and myotonia.
      Compensatory techniques and strategies are mostly offered as the only
      intervention therapy. In the present study, the participants were their own
      controls using pre- and post-test measures. Each participant was tested at
      intervals a total of nine times before and nine times after hand training. A hand
      held myometer (Microfet2), Grippit, Purdue Pegboard and self-rated myotonia were
      used as outcome measures. Occupational performance was assessed pre- and post
      test using the Canadian Occupational Performance Measurement (COPM) in which the
      participants rated their own performance and satisfaction in five self-chosen
      occupational performance areas. The participants performed hand training for a
      total of three months, three times per week using a specific resistance training
      programme including Theraputty, a silicone-based putty. Hand function was
      significantly increased and a positive change in self-rated occupational
      performance was noted after the training period. This study indicates that hand
      training has a positive effect on hand function, i.e. motor function and
      occupational performance. The present results need to be replicated in a
      controlled study including a larger number of patients and over a longer period
      of time.

PMID- 15962698
TI  - A strategy for supervising occupational therapy students at community sites.
AB  - Within the field of occupational therapy various innovative strategies have been
      used to provide students with effective clinical education (fieldwork)
      opportunities. One of the more unusual strategies involves the student
      participating in a placement at a site where there is no occupational therapist
      and no well-defined role. The University of Alberta, Canada developed and piloted
      a new fieldwork supervisory position. Feedback was collected from both the sites
      and students to explore the impact of this position on the fieldwork experience
      for stakeholders. As well, sites and students were asked to give their opinions
      on more general aspects of these placements. Both sites and students positively
      endorsed the fieldwork educator for independent community placement's role. Most
      recommendations for improvement revolved around increasing the time dedicated to
      this position and making it permanent. Caution must be taken in generalizing the
      results of this study, as there may be various considerations that make this an
      appropriate supervision strategy in Alberta, Canada but not in other locations.
      Further research is required to determine whether this supervision strategy could
      be used with other students or professions in other locations.

PMID- 15962699
TI  - Changes in accessibility and usability in housing: an exploration of the housing
      adaptation process.
AB  - The purpose of a housing adaptation is to enhance daily activities and to improve
      housing accessibility and usability by removing physical barriers in the home.
      The aim of this study was to investigate longitudinal changes in housing
      accessibility among clients receiving grants for housing adaptations. Baseline
      assessments were administered one month before the housing adaptation, with the
      first follow-up after two to three months, and the second follow-up after eight
      to nine months. The Housing Enabler and the Usability in My Home instruments were
      used to collect data from 131 consecutively enrolled clients living in general
      housing. Accessibility and usability improved significantly, the number of
      physical environmental barriers decreased and dependence on mobility devices
      increased, but at different times along the process. The results indicate the
      complexity of the housing adaptation process and the need to consider person
      environment interactions over time. The methodology seems useful for quality
      development of assessment, intervention and evaluation processes in housing
      adaptations performed by occupational therapists.

PMID- 15962700
TI  - The influence of executive functions, sensation seeking, and HIV serostatus on
      the risky sexual practices of substance-dependent individuals.
AB  - From a public health standpoint, identifying factors that contribute to risky
      sexual practices among substance-dependent individuals is critical, particularly
      in the context of HIV infection. This study examines the respective contributions
      of executive neurocognitive functions, sensation seeking, and HIV serostatus in
      predicting risky sexual practices among poly-substance users (with a history of
      dependence primarily for cocaine or cocaine/heroin). HIV+ (n=109) and HIV-
      (n=154) substance-dependent individuals were assessed using three neurocognitive
      tasks of executive functions: Stroop reaction time, delayed non-matching to
      sample, and the Iowa Gambling Task. Sensation seeking was assessed using the
      Sensation Seeking Scale-V. Greater sensation seeking was associated with more
      risky sexual practices among HIV+ participants, particularly among those who
      performed best on the Iowa Gambling Task. Our findings indicate that continued
      risk behavior among HIV+ drug users may be driven by sensation seeking (a
      personality trait common among drug users); however, the impact of executive
      functions is less clear.

PMID- 15962701
TI  - Semantic priming in patients with right frontal lobe lesions.
AB  - Patients with unilateral, right frontal lobe damage (N=13) and matched controls
      (N=20) performed a task of lexical ambiguity resolution in order to explore the
      contribution of right frontal regions to lexical-semantic priming. Word triplets
      consisting of balanced homographs were presented to participants in four
      conditions: concordant, discordant, neutral, and unrelated. Controls demonstrated
      facilitation for concordant meanings of homographs, as evidenced by their faster
      reaction times in the concordant relative to the unrelated (baseline) condition,
      as well as a lack of facilitation for the discordant meaning relative to the
      neutral and concordant conditions. Results in patients with right frontal lobe
      damage differed depending on the site of the lesion. Patients with lesions
      restricted to the right medial frontal lobe only showed facilitation in the
      neutral condition, while those with lesions encroaching upon the right
      dorsolateral region demonstrated facilitation of both discordant and concordant
      meanings relative to the baseline condition. These results support a role for the
      right frontal lobe in semantic priming and suggest possible specialization within
      the right prefrontal cortex for the processing of lexical-semantic information.

PMID- 15962702
TI  - The contribution of implicit and explicit memory to the effects of errorless
      learning: a comparison between young and older adults.
AB  - There is evidence that the prevention of errors during learning might be helpful
      in improving an impaired memory performance, both in amnesia as well as in normal
      age-related memory decline. Although errorless learning is a promising technique
      for use in rehabilitation practice, the underlying mechanisms are unclear. That
      is, it has been suggested that the beneficial effects of errorless learning
      operate through implicit memory, whereas others implicate that it is explicit
      memory that is responsible for the enhanced memory performance after errorless
      learning. The current study examined the contribution of implicit and explicit
      memory function to the memory performance after errorless and errorful learning
      using the process-dissociation procedure. A group of young adults (N=40) was
      compared to a matched group of older individuals (N=40) on a spatial memory task
      (i.e., learning the locations of everyday objects in a room). The results clearly
      show age-related decline in explicit spatial memory, while implicit spatial
      memory was unaffected. Furthermore, the young group benefited from errorless
      learning compared to errorful learning, while the older group did not show a
      difference between the two learning conditions. Also, it was found that the
      effects of errorful learning were related to explicit memory function, and not
      implicit processing, corroborating and extending recent findings.

PMID- 15962703
TI  - Verbal memory in first-episode schizophrenia: heterogeneity in performance?
AB  - It is unclear if the commonly observed "subcortical" verbal memory profile in
      schizophrenic patients is present at the onset of the disease. Therefore, the
      performance of 43 first-episode patients with schizophrenia or schizophreniform
      disorder on the Dutch version of the California Verbal Learning Test (VLGT) was
      compared to that of 43 normal comparison participants. We hypothesized that the
      first-episode patients would exhibit a "subcortical" memory profile, that is,
      they would show a primary retrieval deficit. This hypothesis was not confirmed:
      the patients displayed a profile suggestive of a prominent storage deficit, that
      is, a "cortical" memory profile. Subsequently, patients' VLGT performance was
      cluster analyzed to determine whether subgroups could be identified exhibiting a
      cortical, subcortical, and normal profile, respectively. Two subgroups (N=22;
      N=13) exhibited memory impairments, while one subgroup (N=8) was unimpaired. The
      memory profiles of the two impaired subgroups differed both qualitatively and
      quantitatively, but did not conform neatly to a cortical and a subcortical
      profile. Demographic and verbal fluency data provided limited validation of the
      subgroup classification. Our results may suggest that combining the verbal memory
      performance of first-episode patients obscures meaningful heterogeneity.
      Alternatively, the cluster solution could merely reflect a continuum of severity.

PMID- 15962704
TI  - Working memory and inhibitory control among manic and euthymic patients with
      bipolar disorder.
AB  - Bipolar disorder (BPD) is a severe psychiatric illness that is characterized by
      episodes of extreme mood states. The affective components of bipolar disorder
      have been studied extensively, but only recently have investigators begun to
      systematically examine its cognitive concomitants. Although executive dysfunction
      has been reported in this population, especially while patients are manic, the
      tasks administered in many previous studies have made it difficult to determine
      the specific executive abilities that were compromised. The present study
      examined 15 patients with bipolar disorder who were manic, 18 who were euthymic,
      and 18 healthy participants. Tests were selected to evaluate two specific aspects
      of executive functioning in these participants. The Object Alternation Task was
      given as a measure of inhibitory control, and the Delayed Response Task was
      included as a measure of spatial delayed working memory. All groups performed
      similarly on the Delayed Response Task. On the Object Alternation Task, however,
      the manic and euthymic patients committed significantly more perseverative errors
      than healthy participants. These results indicated that patients in the present
      sample had relatively normal working memory abilities, but had a deficit in
      behavioral self-regulation, which was evident across mood states.

PMID- 15962705
TI  - Speed, speed variability, and accuracy of information processing in 5 to 6-year
      old children at risk of ADHD.
AB  - The early assessment of Attention-Deficit/Hyperactivity Disorder (ADHD) children
      has mainly focused on the behavioral, social, and pre-academic impairments. This
      study examined whether 5 to 6-year-old children at risk of ADHD are characterized
      by information-processing deficits. By screening 1317 children in Southern
      Limburg (the Netherlands) with the Child Behavior Checklist, 363 were selected
      and underwent a computerized examination. Eighteen months later, standardized
      psychiatric information was obtained. Thirty-three ADHD children were compared
      with 75 borderline ADHD children, 122 pathological controls, and 133 healthy
      controls. ADHD and borderline ADHD children were slower and more variable in
      their processing speed on all tasks than children with no or other pathology.
      These differences were most pronounced for the divided and focused attention
      tasks. Furthermore, one measure of a state regulation deficit discriminated
      between groups. With regard to accuracy, only the proportion of misses on a go-no
      go task was higher in the ADHD group than in the other groups. Evidence was found
      that ADHD is better seen as a continuum rather than a discrete category. Already
      at a young age, children at risk of ADHD show specific information-processing
      deficits. Deficits in time perception and/or energetic state control in children
      with ADHD may possibly account for subnormal task performance.

PMID- 15962706
TI  - Mayo's older African American normative studies: confirmatory factor analysis of
      a core battery.
AB  - Covariance structure analyses of a core neuropsychological test battery
      consisting of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory
      Scale-Revised, and Auditory Verbal Learning Test have previously identified a 5
      factor model in a sample of cognitively normal White volunteers from Mayo's Older
      Americans Normative Studies (MOANS). The present study sought to replicate this
      factor structure in a sample of 289 cognitively normal, community-dwelling
      African American elders from Mayo's Older African Americans Normative Studies
      (MOAANS). The original 5-factor model was tested against 2 alternative 4-factor
      models and a 6-factor model generated on a substantive basis. Confirmatory factor
      analysis supported the construct validity of this core battery in older African
      Americans by replicating the original 5-factor model of Verbal Comprehension,
      Perceptual Organization, Attention/Concentration, Learning, and Retention as
      viable in the present sample.

PMID- 15962707
TI  - The differential clinical and neurocognitive profiles of COMT SNP rs165599
      genotypes in schizophrenia.

PMID- 15962708
TI  - FLAIR lesion volume in multiple sclerosis: relation to processing speed and
      verbal memory.
AB  - Information processing speed and episodic memory are two commonly affected
      cognitive abilities in MS. Insights into the mechanisms of and relationships
      between these abilities have recently come from structural neuroimaging
      techniques, but few studies have used fluid-attenuated inversion recovery
      (FLAIR), a neuroimaging sequence known to be sensitive to cortical and
      juxtacortical lesions in MS. We hypothesized that a volumetric index of FLAIR
      total lesion volume (TLV) would be associated with slowed processing speed and
      verbal memory dysfunction in MS. Twenty MS patients underwent FLAIR imaging and
      were administered measures of verbal memory and processing speed. Correlational
      and regression analyses indicated that TLV was directly and independently related
      to measures of processing speed and verbal memory, and TLV accounted for 56% of
      the variance in cognitive performance. These findings, considered in the context
      of prior work, suggest that FLAIR TLV is a useful predictor of commonly impaired
      cognitive functions in MS, and shows promise as a functionally relevant biomarker
      for disease status.

PMID- 15962709
TI  - Aerosol-administered alpha-tocopherol attenuates lung inflammation in rats given
      lipopolysaccharide intratracheally.
AB  - Intrapulmonary administration of bacterial lipopolysaccharide (LPS) induces a
      well-characterized lung inflammatory response involving alveolar macrophage
      activation, proinflammatory cytokine elaboration, and neutrophil influx. Vitamin
      E, a lipophilic antioxidant consisting of a family that includes tocopherols and
      tocotrienols, has previously been shown to have a variety of anti-inflammatory
      effects, raising interest in its possible uses in disease prevention or therapy.
      Because aerosol delivery is a specific and rapid way to administer agents to the
      lungs, the authors undertook to determine whether inhaled vitamin E aerosols
      would have an anti-inflammatory effect in the lungs. Using a rat model of acute
      lung inflammation caused by intratracheally administered LPS (10 microg
      Pseudomonas aeruginosa LPS), the authors examined the effect of aerosol
      administered vitamin E, in this case alpha-tocopherol, on several indices of lung
      inflammation which are increased by LPS treatment. It was found that inhaled
      alpha-tocopherol aerosol, but not inhaled alpha-tocopherol acetate aerosol,
      decreased tumor necrosis factor alpha (TNFalpha) and cytokine-induced neutrophil
      chemoattractant-1 (CINC-1) mRNA levels in lung tissue, TNFalpha and CINC-1
      immunoreactive protein levels in lung lavage, and the number of neutrophils
      recoverable by lung lavage from rats given LPS intratracheally. These results
      contribute to the increasing body of work describing immunomodulatory functions
      of alpha-tocopherol, and support the idea that direct aerosol administration of
      alpha-tocopherol may play a beneficial role in strategies to control inflammatory
      lung illnesses.

PMID- 15962710
TI  - Expression and characterization of the intracellular vanilloid receptor (TRPV1)
      in bronchi from patients with chronic cough.
AB  - TRPV1 is a modulator of noxious stimuli known to be important in the cough
      reflex. We have compared the expression of TRPV1 in normal human airways and
      those from patients with chronic cough and found that there is up regulation in
      airways smooth muscle in disease. This increased expression appears to be
      intracellular and we have therefore examined the role of intracellular rat and
      human TRPV1 activity was found using intracellular calcium signalling with human
      intracellular TRPV1 being located in a thapsigargin insensitive compartment.
      Increase in TRPV1 activity may have a role in the airway hypersensitivity seen in
      chronic cough.

PMID- 15962711
TI  - Influence of depletion of alveolar macrophages on apoptosis in Candida-induced
      acute lung injury.
AB  - Apoptosis plays an important role in acute lung injury (ALI), and alveolar
      macrophages (AMs) are known to secrete proinflammatory cytokines and promote
      alveolar inflammation. The authors have previously reported that AMs can be
      depleted by inhalation of 1 mM 2-chloroadenosine (2-CA). In this study, the
      authors evaluated the effect of AM depletion by 2-CA inhalation on apoptosis in
      Candida-induced ALI. The results of in situ terminal deoxynucleotidyl transferase
      mediated dUTP biotin nick end-labeling (TUNEL) and immunohistochemical studies
      and measurement of cytokine levels and caspase 3 activities in lung homogenates
      indicated that the Fas-FasL system and apoptosis of alveolar epithelial cells are
      suppressed by depletion of AMs by 2-CA inhalation.

PMID- 15962712
TI  - Discrimination of resident and infiltrated alveolar macrophages by flow cytometry
      in influenza A virus-infected mice.
AB  - Laser flow cytometric analysis was used in conjunction with in vivo labeling with
      the lipophilic fluorescent dye DiIC18(5)-DS to discriminate resident alveolar
      macrophages from newly infiltrating monocytes/macrophages in mice with and
      without pulmonary influenza A virus infection. Leukocytes in bronchoalveolar
      lavage (BAL) and peripheral blood were analyzed by 2-color flow cytometry as a
      function of time following intravenous injection of DiIC18(5)-DS. At 4 hours, dye
      positive leukocytes were present in both BAL and blood of normal mice, indicating
      that DiIC18(5)-DS rapidly crossed the pulmonary endothelial-epithelial barrier.
      At 4 days after dye injection, 98% of BAL cells were DiIC18(5)-DS positive, and
      almost all of these were monocytes/macrophages based on labeling with fluorescein
      isothiocyanate (FITC)-conjugated antibody to the Mac-3 marker. Only 3.2% +/- 0.3%
      of peripheral blood monocytes (approximately 0.16% of total peripheral blood
      leukocytes) were DiIC18(5)-DS positive at 6 days after injection, whereas > 95%
      of BAL leukocytes were strongly dye-positive on days 6 to 28. When DiIC18(5)-DS
      was injected in mice 6 days prior to intranasal challenge with influenza A, flow
      cytometry indicated that 57.8% 5.6% and 60.7% +/- 8.5% of macrophages/monocytes
      in BAL were newly infiltrated (i.e., DiIC18(5)-DS negative, Mac-3 positive) at 4
      and 7 days, respectively, post viral infection. The discrimination of
      subpopulations of resident and newly recruited macrophages in BAL should
      facilitate future mechanistic studies on pulmonary infection and inflammatory
      lung injury.

PMID- 15962713
TI  - Bioavailability of beryllium oxide particles: an in vitro study in the murine
      J774A.1 macrophage cell line model.
AB  - Beryllium metal and its oxide and alloys are materials of industrial significance
      with recognized adverse effects on worker health. Currently, the degree of risk
      associated with exposure to these materials in the workplace is assessed through
      measurement of beryllium aerosol mass concentration. Compliance with the current
      mass-based occupational exposure limit has proven ineffective at eliminating the
      occurrence of chronic beryllium disease (CBD). The rationale for this research
      was to examine the mechanism of beryllium bioavailability, which may be pertinent
      to risk. The authors tested the hypothesis in vitro that dissolution of particles
      engulfed by macrophages is greater than dissolution in cellular medium alone.
      Physicochemical changes were evaluated in vitro for well-characterized high
      purity beryllium oxide (BeO) particles in cell-free media alone and engulfed by
      and retained within murine J774A.1 monocyte-macrophage cells. The BeO particles
      were from a commercially available powder and consisted of diffuse clusters
      (aerodynamic diameter range 1.5 to 2.5 microm) of 200-nm diameter primary
      particles. Following incubation for 124 to 144 hours, particles were recovered
      and recharacterized. Recovered particles were similar in morphology, chemical
      composition, and size relative to the original material, confirming the
      relatively insoluble nature of the BeO particles. Measurable levels of dissolved
      beryllium, representing 0.3% to 4.8% of the estimated total beryllium mass added,
      were measured in the recovered intracellular fluid. Dissolved beryllium was not
      detected in the extracellular media. The BeO chemical dissolution rate constant
      in the J774A. 1 cells was 2.1 +/- 1.7 x 10(-8)g/(cm2 . day). In contrast, the BeO
      chemical dissolution rate constant in cell-free media was < 8.1 x 10(-9)g/(cm2 .
      day). In vivo, beryllium dissolved by macrophages may be released in the
      pulmonary alveolar environment, in the lymphatic system after transport of
      beryllium by macrophages, or in the alveolar interstitium after migration and
      dissolution of beryllium particles in tissue. These findings demonstrate a
      mechanism of bioavailability for beryllium, are consistent with previously
      observed results in canine alveolar macrophages, and provide insights into
      additional research needs to understand and prevent beryllium sensitization and
      CBD.

PMID- 15962714
TI  - Double-stranded RNA stimulates the expression of monocyte chemoattractant protein
      1 in BEAS-2B bronchial epithelial cells.
AB  - BEAS-2B bronchial epithelial cells were treated with polyinosinic-polycytidylic
      acid (poly IC), a synthetic double-stranded RNA (dsRNA) analog, and the
      expressions of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein were
      analyzed by reverse transcriptase-polymerase chain reaction and enzyme-linked
      immunosorbent assay. Poly IC enhanced the expression of MCP-1 and release of
      mononuclear cell chemotactic activity, which were inhibited by dexamethasone pre
      treatment. The poly IC-induced up-regulation of MCP-1 was blocked by 2
      aminopurine, a specific inhibitor of dsRNA-dependent protein kinase, but not by
      nuclear factor (NF)-kappaB inhibitor SN50.

PMID- 15962715
TI  - The influence of sex differences and social environment on the occurrence of
      psychosomatic disorders.

PMID- 15962716
TI  - Proposal of practicing Japanese Kampo in menopausal medicine.
AB  - Traditional Chinese Medicine (TCM) is now called "Kampo Medicine" in Japan. What
      is really needed for the treatment of human sickness and what is really wanted by
      sick people is medical care tailored to the particular patient, which respects
      the individual characteristics and personality of the patient. In Kampo medicine,
      therapeutic policy is determined on the basis of the physical constitution and
      condition of individual patients. For this reason, Kampo medicine is called
      "tailor-made medicine." One characteristic of Kampo medicine is that it is aimed
      at treating conditions preceding disease. The diagnosis system of Kampo medicine
      therefore includes identification of the personality of each patient and
      correction of its distortion, if any. Women with undefined complaints in the
      climacteric period often have multiple symptoms. To identify the characteristics
      of each patient and to provide treatment tailored to each patient, SHO diagnosis
      is needed. This diagnostic process is unique to Kampo medicine and is not
      included in modern Western medicine. Making full use of the traditional
      diagnostic approach of Kampo medicine, SHO is determined and the patient's
      condition is understood from the standpoint of Kampo medicine. Optimum treatment
      is then provided on the basis of such understanding of the patient and his or her
      illness. Kampo medicine is established as a science with art. Practicing Kampo
      medicine involves dealing with patients using a science with art and thus
      providing humane medical care to patients. Kampo medicine is thus of use to all
      the world.

PMID- 15962717
TI  - Trauma and grief 2-7 years after termination of pregnancy because of fetal
      anomalies--a pilot study.
AB  - The aim of the study was to obtain information on the long-term posttraumatic
      stress response and grief several years after termination of pregnancy due to
      fetal malformation. We investigated 83 women who had undergone termination of
      pregnancy between 1995 and 1999 and compared them with 60 women 14 days after
      termination of pregnancy and 65 women after the spontaneous delivery of a full
      term healthy child. Women 2-7 years after termination of pregnancy were expected
      to show a significantly lower degree of traumatic experience and grief than women
      14 days after termination of pregnancy. Contrary to the hypothesis, however, the
      results showed no significant intergroup differences with respect to the degree
      of traumatic experience. With the exception of one subscale (fear of loss), this
      also applied to the grief reported by the women. However, both groups differed
      significantly in their posttraumatic stress response from women who had given
      spontaneous birth to a full-term healthy child. The results indicate that
      termination of pregnancy is to be seen as an emotionally traumatic major life
      event which leads to severe posttraumatic stress response and intense grief
      reactions that are still detectable some years later.

PMID- 15962718
TI  - Semen providers and their three families.
AB  - BACKGROUND: In 1985 the Swedish government introduced legislation that required
      all semen providers to furnish identifying information on themselves which would
      then be made available to their biological/provider offspring when they are
      deemed to have 'sufficient maturity'. The purpose of the legislation was to
      protect the child's rights and needs. The aim of this paper is to examine the
      degree to which semen providers have considered the implications of their
      decision to donate upon their three families; their birth family, the family they
      form with their partner, and the recipient family. METHODS: Thirty semen
      providers from two Swedish clinics were sent self-completion questionnaires
      collecting both quantitative and qualitative information. The initial response
      rate was 100%. Questions requested demographic information; the degree to which
      semen providers had consulted with or advised their partners, family, existing
      offspring and acquaintances about their semen donation; views and attitudes of
      semen providers towards donor offspring, anonymity, information sharing, payments
      to semen providers, community acceptance of DI and semen providers, experience of
      donation, recruitment/screening procedures. RESULTS: Almost all respondents had
      told their partners that they were providing semen, however, a much smaller
      proportion had told their birth families. Almost two thirds of semen providers
      were positive or very positive about the prospect of meeting their offspring at
      some time in the future, with older men expressing more enthusiasm. CONCLUSIONS:
      The findings suggest that semen providers have only partially considered and
      addressed the full implications of having semen provider offspring. The age of
      semen providers could be influential in determining some attitudes and views.

PMID- 15962719
TI  - Emotional impact and acceptability of medical abortion with mifepristone: a
      German experience.
AB  - In Germany, four years of experience with mifepristone as an alternative
      procedure to surgical abortion have revealed a still reluctant use of the new
      method. In the public discussion, the more participatory role of the women in the
      abortion procedure is often feared to have negative consequences for the
      emotional processing of the event. This study compares the women's criteria for
      selecting a method and the psychological responses before and four weeks after
      medical or surgical abortion. Two hundred and nineteen women answered questions
      regarding demographic data, motivation, medical details and social support.
      Additionally, the women completed the Hospital Anxiety and Depression Scale
      (HADS) and the Impact of Event Scale (IES). There were no differences regarding
      sociodemographic and reproductive characteristics among both groups. Comparing
      data before and a month after the abortion, our study showed a significant
      decline of both anxiety and depression for both abortion methods. The medical
      group had significantly lower entrance levels of anxiety than the surgical group.
      The medical regimen caused significantly more sequelae such as prolonged
      bleeding, pain and other side effects. However, this did not have a negative
      influence on the coping process. A vast majority of women in both groups
      evaluated choosing between different abortion methods as being highly important
      to them. Our study supports the consensus view that termination of an unwanted
      pregnancy is a positive first solution to the conflict, regardless of the chosen
      method. The positive outcome and high satisfaction levels among the participants
      illustrate the importance of an ongoing and improved accessibility of medical
      abortion for women in Germany.

PMID- 15962720
TI  - Obesity as a risk factor for premenstrual syndrome.
AB  - PURPOSE: To determine the association between obesity and Premenstrual Syndrome
      (PMS). METHODS: A cross-sectional study was conducted using a random-digit
      dialing method. The sampling frame consisted of all possible area codes,
      exchanges, and 4-digit suffixes in Virginia. A total of 874 women between the
      ages of 18-44 residing in the state of Virginia between August 1 and September
      15, 1994 were interviewed. Cases were defined as women who reported severe or
      extreme PMS symptom changes using the Shortened Premenstrual Assessment Form. The
      main exposure variable was obesity as measured by Body Mass Index. RESULTS: The
      prevalence of PMS in Virginia was 10.3 percent. Obese women (BMI > or = 30) had
      nearly a three-fold increased risk for PMS than non-obese women OR = 2.8 (95% CI
      = 1.1, 7.2). PMS was more prevalent among whites, younger women, and smokers.
      CONCLUSION: This data provided evidence that obesity is strongly associated with
      PMS. Since obesity is a modifiable risk factor, PMS management strategies should
      not only consider factors such as, high stress, and smoking but also obesity.

PMID- 15962721
TI  - Obstetrician-gynecologists' decision making about the diagnosis of major
      depressive disorder and premenstrual dysphoric disorder.
AB  - Major depressive disorder (MDD) is underdiagnosed and undertreated in ambulatory
      care settings including gynecologic practices. Far less is known about the
      diagnosis of Premenstrual Dysphoric Disorder (PMDD). Three hundred and thirty
      five gynecologists responded to mailed questionnaires that used descriptive
      scenarios as analogues to clinical cases. Questionnaire recipients were randomly
      selected to receive either a MDD or PMDD version of the questionnaire.
      Respondents were less accurate when diagnosing MDD cases (48% accuracy; p =
      0.526), than PMDD cases (80% accuracy; p < 0.001), but were significantly more
      confident about their probability ratings of MDD cases, t = 2.57, p < 0.02.
      Qualitative analysis suggested that less accurate MDD respondents did not
      prioritize case data according to DSM-IV criteria, whereas almost all PMDD
      respondents made use of valid reasoning strategies. Respondents did not take base
      rates into account when deciding about the probability of either affective
      disorder. Results imply that gynecologists employ cognitive strategies that
      result in accurate diagnostic judgments about PMDD, but overconfidence, lack of
      attention to DSM-IV criteria and base rate neglect could hinder clinical
      decisions about MDD, and may contribute to underdiagnosis of depression.

PMID- 15962722
TI  - The integration of a woman's perspective in hysterectomy decisions.
AB  - It has been argued, based on a limited amount of research data, that patient
      participation in decision-making regarding surgery, results not only in more
      patient satisfaction, but also in better surgery outcomes. Especially in a
      procedure such as hysterectomy, with far-reaching consequences and many potential
      side effects, it may therefore be relevant to promote an active role of the
      patient in the decision-making process. The article identifies contextual
      elements that might promote this active role. Subsequently a model of
      participative, informed decision-making is outlined. The model entails that
      clinical guidelines should be adjusted to the particular situation at hand and
      that patients should be fully informed about hysterectomy-involved risks. An
      overview of the various guidelines and risks is provided. Proper counseling in
      the decision-making phase as well as in the post-hysterectomy period is
      advocated. Throughout the article attention is paid to documented and
      undocumented ethnic differences regarding various aspects of hysterectomy,
      particularly differences in patient participation around the world.

PMID- 15962723
TI  - Experiential factors associated with childbirth-related fear in Swedish women and
      men: a population based study.
AB  - The aim of this study was to investigate and compare experiential factors
      associated with childbirth-related fear in women and in men. A questionnaire was
      completed by 410 women and 329 men who prior to the study had had a healthy baby
      at Umea university hospital, Sweden. The level of fear was estimated, and twenty
      nine statements designed to measure experiences and perceptions connected to
      childbirth and childbirth-related fear, were subjected to exploratory factor
      analysis. Factor scores were calculated and differences among women and men with
      intense and mild/moderate fear were estimated. Intense fear was reported by 23%
      of the women and 13% of the men. The factor analysis identified four factors
      explaining 52% of the variance in woman and 50% in men. The factors were named
      'exposedness and inferiority', 'communicative difficulties', 'norms of harmony'
      and 'insecurity and danger'. The relative order of the factors varied in relation
      to gender, and in the women, 'exposedness and inferiority' had the greatest
      explanatory power, while this was true for 'communicative difficulties' in the
      men. Most factors were reported to a significantly higher extent by respondents
      with intense fear. The results are discussed from a gender perspective.

PMID- 15962724
TI  - Reproduce and die! Why aging? Part I.
AB  - In multi-cellular organisms--and hence also in man--aging and dying is the fate
      of the soma, i.e., the body proper; germ cells are--at least in principle-
      immortal. As the soma can be considered to be the "service compartment" of the
      germ cells, it loses its function once a species' phase of reproduction is over.
      Hence, there is an intimate relationship between reproduction and aging, and
      therefore also between a species' reproductive strategy and aging: there has been
      no selection for maintenance of the soma beyond the reproductive phase of life
      (when there is no reproduction, there is also no natural selection). As a
      consequence, mechanisms, important for maintenance of the soma during the
      reproductive phase, increasingly begin to fail once this phase is over, resulting
      in an accumulation of all kinds of pathology and genetic errors, rendering an
      individual increasingly more prone to a variety of (internal and external)
      attacks. In the end, the soma collapses, be it due to organ failure, a neoplasm
      or to a final external push, e.g., an infection.

PMID- 15962725
TI  - Sex differences in mortality, a comparison of the United Kingdom and other
      developed countries.
AB  - Women, on average, live longer than men, though sex differences in mortality vary
      from country to country and over time. This study includes a description of
      recent changes in life expectancies at different ages, followed by a more
      detailed analysis of death rates by age in selected countries. Additionally it
      provides a historical perspective on the sex differences in mortality in France
      and England and Wales. Possible explanations for the differences among countries
      are explored using trends in mortality by cause of death.

PMID- 15962726
TI  - Review of sources and methods to monitor healthy life expectancy.
AB  - This article presents the rationale for proposed changes in the methods used to
      calculate Healthy Life Expectancy (HLE). HLE is currently calculated for Great
      Britain and England based on data from the General Household Survey (GHS). The
      proposed revisions have been prompted by three sets of changes reflecting
      improvements to sources and methods. Changes in GHS methodology and survey
      coverage which affect estimates of the rates of ill-health in the
      noninstitutional population. Availability of data from the 2001 Census to update
      estimates of the ill-health rates and the size of the institutional population.
      Inclusion of data from the Continuous Household Survey of Northern Ireland (CHS
      NI) to produce a HLE estimate for the UK.

PMID- 15962727
TI  - Death certification: issues from a pilot of the Shipman Inquiry's interim
      proposals.
AB  - This article investigates the issue of death certification in England and Wales.
      The Shipman Inquiry published interim proposals designed to make the system of
      death certification safer and more accurate. The proposed forms were piloted by
      doctors and relatives on a sample of deaths in one locality. They were then
      interviewed to assess the forms' feasibility and acceptability.

PMID- 15962728
TI  - Conceptions in England and Wales, 2003.

PMID- 15962729
TI  - Death registrations in England and Wales, 2004: causes.

PMID- 15962730
TI  - Role of intralesional bleomycin in the treatment of complicated hemangiomas:
      prospective clinical study.
AB  - BACKGROUND: Hemangioma is the most common tumor of infancy. Although it has a
      basically benign nature and usually spontaneously regresses, a small percentage
      (5%) have complications that need treatment. Many different therapeutic
      modalities can be used in this tumor. OBJECTIVE: To investigate the effect of a
      new method of treatment (intralesional bleomycin injection) in complicated
      hemangiomas. MATERIALS AND METHODS: In the Department of Radiation Oncology at
      Nemazee Hospital in Shiraz, Iran, from April 1992 to October 1998, 32 patients
      with complicated hemangioma were treated with four to six courses of direct
      injection of bleomycin into the lesion. RESULTS: After a minimum follow-up of 6
      years, there was 70 to 100% regression in 18 patients, 50 to 70% in 7 cases, and
      less than 50% reduction in 7 patients. CONCLUSION: Intralesional injection of
      bleomycin is an easy, safe, and effective therapeutic modality in complicated
      cutaneous hemangiomas.

PMID- 15962731
TI  - Effects of botulinum toxin type A on contouring of the lower face.
AB  - BACKGROUND: Masseteric muscle hypertrophy is an uncommon dition represented as a
      swelling of the masseter muscle. Recent reports have demonstrated the successful
      use of botulinum in the treatment of masseteric hypertrophy. OBJECTIVE: This
      study was a prospective trial to evaluate the effectiveness of botulinum toxin
      type A (Botox) in the treatment of masseteric muscle hypertrophy according to
      doses of 10, 20, and 30 U. MATERIALS AND METHODS: Twenty-two patients were
      referred to the dermatologic clinic for the management of masseteric muscle
      hypertrophy. Ultrasonographic measurements of the thickness of the masseter
      muscle were performed, and clinical photographs were taken before treatment and
      1, 2, 3, 4, 6, and 9 months after the treatment. RESULTS. The median values of
      percentage reduction of muscle mass were 10.3%, 16.5%, 23.7%, 24.7%, 21.6%, 16.5%
      in the 10 U group; 11.9%, 18.8%, 24.8%, 27.7%, 26.7%, and 21.8% in the 20 U
      group; and 12.0%, 19.4%, 25.0%, 27.8%, 37.8%, and 24.1% in the 30 U group.
      CONCLUSION. The adequate dose of botulinum toxin type A for treatment of
      masseteric muscle hypertrophy should be above 20 U. The effect of botulinum toxin
      type A is maintained for at least 9 months as the treatment of masseteric muscle
      hypertrophy.

PMID- 15962732
TI  - Outcomes of 532 nm frequency-doubled Nd:YAG laser use in the treatment of port
      wine stains.
AB  - BACKGROUND: Port-wine stains (PWSs) are congenital dermal malformations involving
      venules, capillaries, and, probably, perivascular nerves. The primary morbidities
      of PWS are psychological disturbances that adversely affect the development of
      personality. Lasers have been the treatment of choice for PWS. However, only one
      type of laser is not a panacea for all PWS malformations. For the treatment of
      PWSs, carbon dioxide, argon, krypton, copper bromide, frequency-doubled
      neodymium:yttrium-aluminum-garnet (Nd:YAG), flashlamp pumped pulsed dye laser,
      and also intense pulsed light sources can be used. OBJECTIVE: To determine the
      efficacy and the frequency of side effects of the frequency-doubled Nd:YAG laser
      for the treatment of PWSs. PATIENTS AND METHODS: In this study, 532 nm frequency
      doubled Nd:YAG laser with a 2 to 6 mm spot size, 15- to 50-millisecond pulse
      width, and a 9.5 to 20 J/cm2 fluence was applied for 89 patients (62 female, 27
      male; age range 3-49 years) with PWSs on the face and/or neck for 1 to 12
      sessions, with 2-month treatment-free intervals. Improvement rates were
      considered a failure (< 25%), mild (25-49%), moderate (50-74%), good (75-94%),
      and excellent (> 95%). RESULTS: Excellent (n = 12; 13%), good (n = 34; 38%),
      moderate (n = 39; 44%), and mild (n = 4; 5%) improvement of lesions was obtained
      after an average of 5.6, 5.5, 4.4, and 3.8 therapy sessions, respectively. No
      treatment failure was observed for any patient. As adverse effects, transient
      hyperpigmentation (n = 2; 2.25%), hypopigmentation (n = 1; 1.12%), and
      hypotrophic scarring (n = 1; 1.12%) were noted. CONCLUSIONS: The results obtained
      asserted that the frequency-doubled Nd:YAG laser is a quick, safe, and effective
      treatment modality for PWS malformations and can be appreciated as a useful
      alternative therapy that can raise the rates of success in cases with PWSs
      refractory to other laser therapies.

PMID- 15962733
TI  - Treatment of congenital nevomelanocytic nevi with the CO2 and Q-switched
      alexandrite lasers.
AB  - BACKGROUND: A variety of treatment options exist for the management of congenital
      nevomelanocytic nevi (CNN). Surgical treatment has been the traditional approach,
      but scarring and cosmetic problems are common. Recently, lasers have been used to
      treat CNN because, in some cases, surgical excisions are inadequate owing to
      their inaccessible location, size, and depth. OBJECTIVE: The effects of the
      combined use of CO2 laser and Q-switched Alexandrite laser on CNN were evaluated.
      METHODS: Eleven patients with CNN were enrolled in this study. The surface
      epithelium was abraded by a CO2 laser. Subsequently, the lesion was treated by a
      Q-switched alexandrite laser. Repeated treatments were done every 6 weeks. The
      results were evaluated clinically by both physicians and patients at 2 and 6
      weeks after each treatment using a 5-point grade scale. RESULTS: By the end of
      the treatments, the average improvement scale assessed by the physicians, with a
      5-point grade scale, was 3.82 and that of the patients was 3.73. There were no
      cases of hypertrophic scar or postinflammatory hyperpigmentaton persisting beyond
      2 weeks. There were no recurrences during the 2-year follow-up period.
      CONCLUSION: The combined laser treatment is an effective method for the treatment
      of CNN. The clinical outcome was favorable; the treatment was safer, less
      painful, and relatively nonscarring; and there was a quicker recovery period and
      less of a burden to repeat treatment when necessary compared with conventional
      treatments.

PMID- 15962734
TI  - Effects of intense pulsed light and the 1,064 nm Nd:YAG laser on sun-damaged
      human skin: histologic and immunohistochemical analysis.
AB  - BACKGROUND: Nonablative methods may produce collagen synthesis in sun-damaged
      skin. OBJECTIVE: To study the effects of intense pulsed light (IPL) and 1,064 nm
      neodymium:yttrium-aluminum-garnet (Nd:YAG) laser: a histologic and
      immunohistochemical analysis of sun-damaged skin. MATERIALS AND METHODS: Nine
      subjects participated. Five subjects received five-monthly treatments with IPL
      (560 nm cutoff filter, 8 x 35 mm spot size, pulse duration 2.4/4.2 milliseconds,
      pulse delay 15 milliseconds, fluence 28-35 J/cm2). Four subjects received
      treatment with a 1,064 nm Nd:YAG laser (130 J/cm2, triple pulse, 7.0/7.0/7.0
      millisecond pulse duration, 75-millisecond delay). Routine histology and
      immunohistochemistry on 2 mm punch biopsies were taken before treatment and then
      at 3 and 6 months. We quantified collagen in the upper dermis and expression of
      heat shock protein 70 and procollagen 1. RESULTS: Pretreatment specimens
      contained solar damage. After treatment with the 1,064 nm Nd:YAG laser, the
      amount of collagen in the papillary dermis was slightly thicker than in those
      subjects treated with the IPL device (nonsignificant differences). Scattered
      dendritic cells in the papillary and upper reticular dermis expressed heat shock
      protein 70 and procollagen 1 after treatment with either light device.
      CONCLUSION: Both the IPL and 1,064 nm Nd:YAG laser-induced heat activation of
      superficial dermal dendritic cells resulted in deposition of collagen in the
      papillary dermis without evident morphologic damage to the epidermis or dermis.

PMID- 15962735
TI  - Is topical anesthesia useful in noninvasive skin tightening using radiofrequency?
AB  - BACKGROUND: The radiofrequency (RF) system has been applied to Asian skin for
      noninvasive skin tightening. The only drawback is the pain during the treatment.
      OBJECTIVE: The relationships between the effectiveness of a topical anesthetic at
      various RF levels and the respective treatment results were compared and assessed
      after 3 months. SUBJECTS AND METHODS: Eighty-four females, ranging in age from 30
      to 60 years, were divided into three groups of 28 subjects each. In all groups,
      the entire bilateral cheeks were treated. Group A underwent RF treatment
      (ThermaCool TC, Thermage, Hayward, CA, USA) with topical anesthesia and group B
      without anesthesia, and in group C, half of the face was treated with anesthesia
      and the other half was not. The degree of pain was recorded. Digital photographs
      of the patients pre- and post-treatment were objectively assessed by double
      blinded physicians. Subjective assessment was performed with questionnaires.
      RESULTS: The average treatment levels for groups A and B were 14.13 and 14.02,
      respectively. Although anesthesia was useful for pain reduction, it did not allow
      a significant energy upgrade. In group C, 8 (28.6%) patients showed a
      statistically insignificant difference in the treatment levels, but not in the
      results, between the anesthetized and the unanesthetized sides. CONCLUSIONS: The
      use of anesthesia did not affect the final efficacy of the treatment compared
      with no anesthesia.

PMID- 15962736
TI  - Accuracy and predictors of basal cell carcinoma diagnosis.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer in the United
      States. Therefore, prospective assessment of dermatologists' acumen in diagnosing
      BCC is important but, unfortunately, is lacking. OBJECTIVE. We sought to
      determine the positive predictive value (PPV) for clinically diagnosing BCC based
      on how confident the physician is of the diagnosis. We also sought to determine
      which clinical and historical factors most influence a dermatologist's perception
      that a tumor is a BCC and to determine which factors are correlated with a lesion
      being a BCC. METHODS: Dermatology attending faculty at the University of Miami
      performing biopsies on their patients in whom BCC was a consideration were asked
      to complete a questionnaire. They recorded how confident they were of their
      clinical diagnosis of BCC. They also recorded various clinical and historical
      factors about the patients and the lesions biopsied. RESULTS: The PPV for
      clinically diagnosing BCC when the clinician was most confident was 80%. Age (>
      64 years) and the presence of pigmentation, telangiectasias, and a pearly border
      were statistically associated with a greater confidence level and a histologic
      diagnosis of BCC. Sunscreen use was associated with fewer diagnoses of BCCs.
      CONCLUSION: This is the first study to determine a relevant PPV for the clinical
      diagnosis of BCC because the PPV was based on clinical confidence level. These
      results highlight the role of diagnostic biopsies, could improve patient
      referral, and may help increase the PPV in the future.

PMID- 15962737
TI  - Detection of residual basal cell carcinoma by in vivo confocal microscopy.
AB  - BACKGROUND: Near-infrared reflectance-mode confocal scanning laser microscopy
      (RCM) represents a novel imaging technique for microscopic analysis of skin
      lesions and may provide a noninvasive modality for the diagnosis of basal cell
      carcinoma (BCC). OBJECTIVE: To determine the feasibility of detecting residual or
      clinically equivocal BCC using RCM. METHODS: In this pilot study, RCM was used in
      three cases to characterize the histologic features of index lesions in vivo.
      These were subsequently correlated with corresponding hematoxylin-eosin-stained
      sections obtained during Mohs micrographic surgery. RESULTS: Evaluation of
      clinically equivocal lesions by RCM revealed features characteristic of BCC,
      including tightly packed nests of elongated, monomorphic, polarized nuclei and
      subjacent ectatic blood vessels with lymphocytes undergoing margination and
      rolling. Conventional histology confirmed the presence of BCC in all cases.
      CONCLUSION: We report the use of RCM in the confirmation of residual BCC in two
      cases and the tentative diagnosis with subsequent pathologic conformation of a
      third case in which a biopsy was previously inadequate. Our results demonstrate
      that confocal microscopy may facilitate diagnosis of BCC in vivo and warrant
      further prospective study to quantify the sensitivity and specificity of this
      rapidly evolving imaging modality.

PMID- 15962738
TI  - Effect of full-thickness skin graft initial dimension on secondary wound
      contraction: experimental study in rats.
AB  - BACKGROUND: The size of a full-thickness skin graft (FTSG) is typically
      determined using a pattern of the defect usually obtained following excision of a
      skin lesion. OBJECTIVE: The aim of this experimental study is to investigate the
      effects of various graft sizes on secondary wound contraction. METHODS: Four 2.5
      x 2.5 cm defects were created on the backs of 20 rats. Defect A was left to heal
      by secondary intention. The graft obtained from defect B (exact size graft) was
      sutured to its original bed. The wound of defect C (large graft) was patterned,
      and this was used to obtain a generous graft from the abdomen. A presized 1.5 x
      1.5 graft obtained from defect D (small graft) was sutured to its original wound.
      Graft areas on days 0, 3, 7, 10, 14, 18, and 21 were calculated and converted
      into a percentage of the original wound size. Analysis of variance was used for
      statistical comparison. Open wounds reached a final wound size of 5% at day 21.
      Exact-size grafts showed the least secondary contraction rate (74.19 +/- 4.30 %)
      (p < .05). CONCLUSION: A graft in the size of a planned excision preserves its
      original area better than grafts larger or smaller in size in the rodent model.
      The size of a FTSG is an important factor in preventing secondary wound
      contraction. However, it should be stressed that the results of this study cannot
      necessarily be extrapolated to real clinical scenarios without further detailed
      studies.

PMID- 15962739
TI  - Prefabricated nasolabial flap for reconstruction of full-thickness distal nasal
      defects.
AB  - BACKGROUND: The reconstruction of full-thickness nasal tip and alar defects is
      challenging owing to the distal nose's triple-layer structure: skin, cartilage,
      and mucosa. OBJECTIVE: In the reconstruction of wounds of the distal half of the
      nose involving the rim, the most important issue to be considered is to provide a
      good functional and an acceptable esthetic result. Various local and distant
      flaps have been described for this purpose. The nasolabial flap is one of the
      most frequently used flaps in reconstruction of small- to moderate-size distal
      nasal defects. Its reliable blood supply, minimal donor site morbidity, and
      excellent texture and color match are some of the advantages of this local flap.
      METHODS: In this study, superiorly based subcutaneous pedicled nasolabial flaps
      have been prefabricated with cartilage and skin grafts. This method has been used
      in 10 cases. RESULTS: One patient had partial flap necrosis, and two patients
      experienced hyperpigmentation on the suture line. Scar revision was performed in
      one patient for hypertrophic scar tissue at the flap margins. No other
      complications were seen in the remaining patients. None of the patients
      experienced a skin graft loss or cartilage exposure. CONCLUSION: The
      prefabricated nasolabial flap offers a superior esthetic and functional result
      and may be an appropriate reconstructive option in reconstruction of small- to
      moderate-size distal nasal defects.

PMID- 15962740
TI  - Body dysmorphic disorder.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is a syndrome characterized by
      distress secondary to imagined or minor defects in one's appearance. Although it
      is a psychiatric disorder, most affected patients present to the dermatologist or
      plastic surgeon to improve their perceived defect. OBJECTIVE: The objective was
      to review the literature on BDD, examining the epidemiology, etiology, clinical
      features, diagnostic criteria, and treatment of the disorder. METHODS: Three
      representative cases of BDD are presented; in addition, a search of MEDLINE was
      completed and a review of all published data on BDD was performed. RESULTS: BDD
      has an estimated prevalence of 1 to 2% in the general population; this prevalence
      is increased in patient populations. There is significant comorbidity associated
      with BDD. CONCLUSIONS: BDD is a relatively common psychiatric disorder in which
      patients typically present to cosmetic surgeons for treatment of their perceived
      or imagined defect. Surgical treatments usually prove unsatisfactory to the
      patient and to the practitioner. Psychiatric treatment is extremely challenging.

PMID- 15962741
TI  - Body dysmorphic disorder and the liposuction patient.
AB  - BACKGROUND: Body dysmorphic disorder (BDD) is an under-recognized disorder that
      affects a sizeable number of patients who seek cosmetic enhancement, in
      particular liposuction. Understanding and recognizing BDD can positively impact
      the care delivered to patients. OBJECTIVE: To familiarize physicians with the
      presenting signs of BDD and present strategies for caring for BDD patients in a
      liposuction and/or cosmetic surgery practice. METHODS: Review of currently
      available literature and diagnostic criteria. RESULTS: BDD affects approximately
      1% of patients in the United States, but as many as 7 to 15% of patients seeking
      cosmetic surgery. Patients with BDD will usually demonstrate an obsession with
      the area they seek treatment of. In addition, patients with BDD present a unique
      challenge to the liposuction surgeon. CONCLUSIONS: Physicians who care for
      patients seeking liposuction or other cosmetic procedures should learn to
      recognize those who have BDD. Proper recognition and counseling of BDD patients
      can have a significant positive impact on not only their care but also on the
      patient-physician relationship. Failure to recognize BDD can, and often does,
      lead to patient dissatisfaction, as well as difficult future interactions with
      the BDD patient.

PMID- 15962742
TI  - Three-dimensional reconstruction of basal cell carcinomas.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common type of skin cancer.
      One of the main problems with BCC is the risk of local recurrence of the tumor
      after treatment. This is mainly due to its irregular outgrowths, which cannot be
      detected clinically. OBJECTIVE: To better understand the tumor morphology and
      growth pattern of BCC, we tried to develop a method that provides a precise three
      dimensional model of the tumor. METHODS: Because Mohs surgery provides the best
      overview of the tumor and the tumor margins (both lateral and in depth), the
      reconstruction was based on slides from Mohs surgery. After digitization and
      processing of the slides, the tumor was then surrounded by a Mohs surgeon on a
      computer screen. These selections (lines) were used for a three-dimensional
      reconstruction of the tumor using MedSurf3D software. RESULTS: This method allows
      three-dimensional reconstruction of any given BCC. The MedSurf3D software enables
      visualization of a three-dimensional model of the tissue, which is removed during
      the surgical procedure. CONCLUSIONS: Three-dimensional reconstruction is a
      fascinating tool that might improve our understanding of the behavior, growth
      pattern, and tumor morphology of BCCs. This technique might also be useful in
      other fields of cutaneous oncology, such as the calculation of the tumor volume
      of melanomas.

PMID- 15962743
TI  - "Jigsaw puzzle" advancement flap for repair of a surgical defect involving the
      lateral nasal ala.

PMID- 15962744
TI  - Locking horizontal mattress suture.
AB  - The horizontal mattress suture is useful in wounds in which there is a need for
      wound edge compression to provide hemostasis, closure is under moderate tension,
      or edge eversion is important. Its primary disadvantage is difficult suture
      removal and precise wound edge apposition. We describe a locking horizontal
      mattress technique that facilitates suture removal and provides more control over
      wound edge placement while providing hemostasis, tensile strength, and eversion.

PMID- 15962745
TI  - Horizontal square buried sutures in a two-layered fashion enable direct primary
      closure for small circular wounds without dog-ears on the face.
AB  - BACKGROUND: Dog-ears often lead to lengthening of an excision, and it is
      desirable to avoid them. OBJECTIVE: Facial skin, including the subepidermal
      connective tissue, is flexible and can be used advantageously to minimize dog
      ears using a novel buried suture technique. METHODS: After removing a round
      lesion, the first horizontal square buried suture (HSBS) was deeply placed
      parallel to the longitudinal direction of the defect beneath superficial fascia.
      After the first HSBS was tied, the defect became fusiform but was still largely
      open. The second HSBS was also placed parallel to the longitudinal direction of
      the defect but in more superficial fascia and using smaller horizontal buried
      loops than those of the first deep suture. After the second HSBS in the middle of
      the dermis was tied, the wound was almost closed without dog-ears. Consequently,
      few skin sutures were required to finish the operation. CONCLUSIONS: Using this
      technique, a small circular or oval defect on the face up to 1 cm in diameter can
      be closed without any additional excision of the skin and without creating dog
      ears.

PMID- 15962746
TI  - Angioedema acute hypersensitivity reaction to injectable hyaluronic acid.
AB  - BACKGROUND: Injectable hyaluronic acid was introduced to European markets in 1996
      and has demonstrated a high safety profile. We describe the first reported case
      of angioedema-type hypersensitivity following injection of the upper lip with non
      animal-stabilized hyaluronic acid (NASHA) gel. OBJECTIVE: To report a case and
      discuss a potential mechanism for and treatment of angioedema-type
      hypersensitivity following injection with NASHA gel into the upper lip. METHODS
      AND MATERIALS: Not applicable. RESULTS: Not applicable. CONCLUSION: Although
      injectable hyaluronic acid has a high safety profile, this reaction is dramatic.
      Treatments and potential mechanisms are discussed.

PMID- 15962747
TI  - Duplex ultrasonography-guided foam sclerotherapy of incompetent perforator veins
      in a patient with bilateral venous leg ulcers.
AB  - BACKGROUND: Recent advances in the form of foam sclerotherapy have extended the
      indications for sclerotherapy in the treatment of varicose veins. OBJECTIVES: (1)
      To see if perforator veins can be closed by using foam sclerotherapy; (2) to
      evaluate whether using foam sclerotherapy for treatment of incompetent perforator
      veins has an influence on venous leg ulcer healing. METHODS: Incompetent
      perforator veins above bilateral venous leg ulcers were treated with duplex
      ultrasonography-guided sclerotherapy using polidocanol foam. RESULTS: After 4
      days, significant improvement in the ulcers was visible; after 10 days, one ulcer
      had closed; and within 3 weeks, both ulcers were closed. Control duplex
      ultrasonography showed closed perforator veins. CONCLUSION: This case illustrates
      that duplex ultrasonography-guided foam sclerotherapy is an effective and
      minimally invasive way of treating incompetent perforator veins. The fast healing
      of the venous leg ulcers in this case report indicates that foam sclerotherapy
      could be a promising addition in the treatment of venous leg ulceration with
      incompetent perforator veins.

PMID- 15962748
TI  - Hair growth induced by diode laser treatment.
AB  - BACKGROUND: Although hair reduction by long-pulsed red and infrared lasers and
      light sources is generally quite effective, paradoxical hair growth has rarely
      been observed following treatment. OBJECTIVE: To report a case of thick hair
      growth following 810 nm diode laser treatment and its subsequent treatment.
      METHODS. A 24-year-old man who had previously had laser hair reduction on his
      posterior neck was treated to a test area on his upper back. RESULTS: Thick
      terminal hair developed in the treated area subsequent to laser treatment.
      Further treatment of this area removed the terminal hair but resulted in terminal
      hair growth in an annular distribution surrounding the treatment site.
      CONCLUSIONS: Diode laser treatment rarely stimulates terminal hair growth. This
      phenomenon should be studied to better understand hair growth cycles and to help
      develop more effective treatments for hair loss and hair growth.

PMID- 15962749
TI  - Pilonidal sinus disease treated by depilation using an 800 nm diode laser and
      review of the literature.
AB  - BACKGROUND: Pilonidal sinus disease is a debilitating, disfiguring chronic
      ailment that is often resistant to therapy. Its etiology and treatment remain in
      question. OBJECTIVE: To assess the efficacy of an 800 nm diode laser in the
      treatment of recalcitrant pilonidal sinus disease. METHODS: Two patients with
      recalcitrant pilonidal sinus disease were treated in the lower back, buttocks,
      and perigluteal cleft area with an 800 nm diode laser with a spot size of 9 x 9
      mm, fluences of 30 to 48 J/cm2, and pulse widths of 15 to 24 milliseconds.
      RESULTS: Long-term relief of pilonidal sinus disease was produced with as few as
      two treatments 2 months apart to as many as six treatments over a 2-year period.
      With each successive treatment, fewer pulses were needed and the interval between
      treatments increased. CONCLUSION: The 800 nm diode laser may be an effective tool
      in the treatment of pilonidal sinus disease. By eliminating the source of hair
      and hair fragments that course along the surface of the lower back and buttocks,
      interruption of the etiologic source for pilonidal sinus disease can be
      accomplished.

PMID- 15962750
TI  - Subungual schwannoma: a rare location.
AB  - BACKGROUND: Schwannoma is a benign tumor of neural tissue and usually develops in
      deeper soft tissue. Cutaneous involvement is uncommon, and a subungual location
      is extremely rare. In fact, it has not been previously reported. OBJECTIVE: To
      present a case of subungual schwannoma. METHOD: A 49-year-old man had a subungual
      tumor on his right thumb of 8 years duration. The lesion caused a mild stinging
      sensation in winter and grew slowly. The tumor was excised using a transungual
      approach. After closure, the wound was dressed with a trimmed original nail
      plate. RESULTS: The nail plate grew normally, and there was no recurrence 1 year
      postoperatively. CONCLUSION: We describe a case of schwannoma that developed in
      the subungual area of a thumb. Although schwannoma rarely develops in this area,
      it should be considered in the differential diagnosis of subungual tumor.

PMID- 15962751
TI  - Staging and assessment of lymph node involvement by 18F-fluorodeoxyglucose
      positron emission tomography in invasive extramammary Paget's disease.
AB  - BACKGROUND: 18F-Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a
      functional and metabolic imaging modality that is efficacious in nodal staging
      and detection of extranodal involvement for malignant tumors. OBJECTIVE: We
      describe the novel use of PET for staging patients with invasive extramammary
      Paget's disease (EMPD) and discuss the potential advantages of this technology
      relative to other diagnostic modalities. METHODS: We evaluated three patients
      with invasive EMPD whose staging was made by PET at Hokkaido University Hospital.
      RESULTS: All lymph nodes detected by PET were over 10 mm. Distant internal
      metastases were not seen in all cases. PET failed to detect 10 and 5 to 7 mm
      nodal involvement but succeeded in detecting nodes over 10 mm. CONCLUSIONS: These
      data suggest that PET may be useful in determining disease activity at the time
      of initial diagnosis but is less useful and proves difficult to detect a small or
      subclinical involvement. This is the first report of PET being used for invasive
      EMPD.

PMID- 15962752
TI  - Perineural spread of squamous cell carcinoma involving the spinal accessory nerve
      in an immunocompromised organ transplant recipient.
AB  - BACKGROUND: Squamous cell carcinoma is the second most common cutaneous
      malignancy in humans, affecting approximately 200,000 people in the United States
      each year. In immunocompromised patients, squamous cell carcinoma is the most
      common skin cancer, and it also tends to behave more aggressively than in
      immunocompetent patients. OBJECTIVE: We describe an immunocompromised patient,
      previously treated for a squamous cell carcinoma of the left posterior shoulder,
      who subsequently developed a cord-like, intraneural metastasis of the spinal
      accessory nerve. RESULTS: The patient presented with a 3-month history of
      lancinating pain of the left neck and shoulder. He had been treated previously
      for a squamous cell carcinoma of the left posterior shoulder, which subsequently
      recurred twice. On examination, a cord-like mass was palpable along the path of
      the spinal accessory nerve. Given the aggressive nature of this patient's
      squamous cell carcinoma, surgical exploration was performed. Frozen-section
      analysis of the spinal accessory nerve and of the multiple supraclavicular nerves
      revealed perineural and intraneural squamous cell carcinoma. CONCLUSION: To our
      knowledge, this is the first reported case of a primary cutaneous squamous cell
      carcinoma of the trunk or extremity metastasizing to a cranial nerve.

PMID- 15962753
TI  - Use of a skin-fat composite graft to prevent alar notching: an alternative to
      delayed postoperative repair.
AB  - BACKGROUND: Full-thickness defects of the alar rim can be challenging to repair
      and often require the use of multistaged interpolated flaps. Alar notching is a
      known complication of these procedures even after cartilage batten grafts have
      been placed to support the alar framework. Standard techniques for repair of alar
      notching involve reinsertion of a cartilage graft, usually at the time of alar
      groove reconstruction 3 months postoperatively. OBJECTIVE: We present a technique
      to prevent alar notching associated with nasolabial interpolation flaps. If early
      notching is noted at the time of pedicle division, preemptive placement of a skin
      fat composite graft can obviate the need for additional procedures. METHODS: A
      case report detailing the procedure and a review of the options for repair of
      alar notching are provided. RESULTS. Placement of a skin-fat composite graft
      harvested from the divided pedicle flap resulted in correction of alar notching.
      CONCLUSION: This procedure is presented as an alternative to delayed cartilage
      grafting for repair of alar rim notching after placement of an interpolated
      pedicle flap. If notching is noted early, correction at the time of pedicle
      division allows for use of available tissue for composite grafting, avoidance of
      a delayed reconstructive procedure, and a good functional and cosmetic

PMID- 15962754
TI  - Repair of the alar groove with combination partial primary closure and second
      intention healing.
AB  - BACKGROUND: The reconstruction of small defects of the alar groove can be a
      unique challenge owing to the importance of maintaining its concave structure.
      OBJECTIVE: To present a report of a patient with a small alar groove defect that
      was repaired using a combination of partial primary closure and second-intention
      healing. METHODS: A 73-year-old female was referred for the treatment of a basal
      cell carcinoma of the right nasal ala and underwent Mohs micrographic surgery
      with clearance of the lesion. The final defect, less than 1 cm, extended to the
      subcutaneous fat. Two absorbable subcutaneous sutures were placed in the defect,
      and the wound was then allowed to heal by second intention. RESULTS. This closure
      yielded a good cosmetic result, with preservation of the alar groove. CONCLUSION:
      A combination of primary closure and second-intention healing is a time
      efficient, low-risk option for nonperforating, small alar groove defects.

PMID- 15962755
TI  - To the editor: Re: Endovascular laser procedures and deep vein thrombosis.

PMID- 15962756
TI  - To the editor: Unilateral nevoid hyperkeratosis of the nipple and areola:
      excellent response to cryotherapy.

PMID- 15962757
TI  - To the editor: Re: Dehisced clean wound: resuture it or Steri-Strip it?

PMID- 15962758
TI  - Extremely low frequency (ELF) magnetic fields and apoptosis: a review.
AB  - In recent years, there has been increasing evidence that extremely low frequency
      magnetic fields might be linked to tumours, particularly with childhood
      leukaemia. In the same period, the role of apoptosis in the tumour process has
      also gained increasing importance. It is the purpose of this review to describe
      the apoptotic process, discuss selected papers in which apoptosis is examined in
      cells exposed to magnetic fields and describe the possible biophysical mechanisms
      responsible for changes in the apoptotic process in exposed cells. Despite some
      differences, as a whole, the literature seems to demonstrate that magnetic fields
      induce changes in apoptosis in cells exposed to different experimental protocols.
      In addition, the important role of ions, particularly of Ca2+, in the apoptotic
      process is also discussed, and one possible model for magnetic field action on
      apoptosis that brings together experimental observations of different nature is
      suggested and discussed.

PMID- 15962759
TI  - Characterization of a complex 125I-induced DNA double-strand break: implications
      for repair.
AB  - PURPOSE: To examine the role of radiation-induced DNA double-strand break (DSB)
      structural organization in DSB repair, and characterize the structural features
      of 125I-induced DSBs that may impact the repair process. METHODS: Plasmid DNA was
      linearized by sequence-specific targeting using an 125I-labeled triplex-forming
      oligonucleotide (TFO). Following isolation from agarose gels, base damage
      structures associated with the DSB ends in plasmids linearized by the 125I-TFO
      were characterized by probing with the E. coli DNA damage-specific endonuclease
      and DNA-glycosylases, endonuclease IV (endo IV), endonuclease III (endo III), and
      formamidopyrimidine-glycosylase (Fpg). RESULTS: Plasmid DNA containing DSBs
      produced by the high-LET-like effects of 125I-TFO has been shown to support at
      least 2-fold lower end joining than gamma-ray linearized plasmid, and this may be
      a consequence of the highly complex structure expected near an 125I-induced DSB
      end. Therefore, to determine if a high density of base damage exists proximal to
      the DSBs produced by 125I-TFOs, short fragments of DNA recovered from the DSB end
      of 125I-TFO-linearized plasmid were enzymatically probed. Base damage and AP site
      clustering was demonstrated within 3 bases downstream and 7 bases upstream of the
      targeted base. Furthermore, the pattern and extent of base damage varied
      depending upon the presence or absence of 2 M DMSO during irradiation.
      CONCLUSIONS: 125I-TFO-induced DSBs exhibit a high degree of base damage
      clustering proximal to the DSB end. At least 60% of the nucleotides within 10 bp
      of the 125I decay site are sensitive to cleavage by endo IV, endo III, or Fpg
      following damage accumulation in the presence of DMSO, whereas > or = 80% are
      sensitive in the absence of DMSO. The high degree of base damage clustering
      associated with the 125I-TFO-induced DSB end may be a major factor leading to its
      negligible in vitro repair by the non-homologous end-joining pathway (NHEJ).

PMID- 15962760
TI  - Correlation between mitotic delay and aberration burden, and their role for the
      analysis of chromosomal damage.
AB  - The aim was to investigate further the relationship between radiation-induced
      mitotic delay and the expression of chromosome damage in V79 cells. Recently
      published data on the time-course of chromosome aberrations in V79 first-cycle
      metaphases after exposure to 10.4 MeV u(-1) Ar ions (LET = 1226 keV microm(-1))
      were supplemented and reanalysed. A statistical analysis of the distribution of
      aberrations among cells was performed. Furthermore, cells were grouped into
      subpopulations carrying 0, 1 -2, 3-4, 5- 6 and 7 or more aberrations. Then, based
      on the mitotic index, the flux of each subgroup through the first mitosis was
      determined and the average entrance time to mitosis was estimated. For
      comparison, the flux of aberrant V79 cells generated by X-irradiation was
      analysed. Analysis of the Ar ion data revealed that the flux of each
      subpopulation through the first mitosis is strongly affected by its aberration
      burden, i.e. a positive correlation between the mitotic delay and the number of
      aberrations carried by a cell was observed. The distribution of aberrations among
      cells could be well described by Neyman-type A statistics; the corresponding fit
      parameters also reflect the damage-dependent mitotic delay. Interestingly,
      comparison of the flux of Ar ion and X-ray-irradiated V79 cells through mitosis
      revealed (1) that a direct correlation exists between the number of aberrations
      carried by a cell and its average entrance time to mitosis, and (2) that this
      effect is independent of the linear energy transfer. The role of these
      observations for radiation cytogenetics is discussed.

PMID- 15962761
TI  - Simple biodosimetry method for use in cases of high-dose radiation exposure that
      scores the chromosome number of Giemsa-stained drug-induced prematurely condensed
      chromosomes (PCC).
AB  - There is a need for quick dose estimation by a simple method in radiation
      accidents. This study develops a simple and rapid dose estimation protocol for
      victims of such accidents, in particular those involving high radiation doses.
      Human peripheral blood lymphocytes (PBL) were gamma-irradiated in vitro at
      several dose points up to 60 Gy, and were stimulated with phytohaemagglutinin-P
      (PHA-P) for 2 days to obtain dividing cells. PBL were then forced to condense
      prematurely, using 50 nM calyculin A, and the obtained chromosome spreads were
      Giemsa stained. The G2-PCC (prematurely condensed chromosomes) index and
      chromosome number for each radiation dose point were scored. G2-PCC were stably
      induced using calyculin A within 24 h delays in stimulation of PBL with PHA-P.
      The chromosome number of G2-PCC increased steeply with radiation doses up to 30
      Gy at a rate of 0.31 Gy(-1) and then decreased at 0.30 Gy(-1) up to 40 Gy. More
      than 10% of G2-PCC index remained up to a 15 Gy dose. Even after 40 Gy
      irradiation, about 2% PCC index was obtained, and this value was enough to score
      a sufficient number of chromosome spreads for analysis. Therefore, the combined
      use of chromosome number and G2-PCC index allows biodosimetry to be done easily
      and rapidly. If PCC are not induced using calyculin A, it is strongly suggested
      that the radiation dose is over 50 Gy. A rapid and easy dose estimation for large
      dose exposure whole-body was realized by combined analysis of Giemsa-stained
      chromosome number of G2-PCC and PCC index using calyculin A. This simple method
      will be of use for rapid decision making of therapy for radiation accident
      victims. This method also has potential for use as a biodosimeter for partial
      body exposure accidents.

PMID- 15962762
TI  - Evaluation of lesion clustering in irradiated plasmid DNA.
AB  - PURPOSE: To measure the yield of DNA strand breaks and clustered lesions in
      plasmid DNA irradiated with protons, helium nuclei, and y-rays. MATERIALS AND
      METHODS: Plasmid DNA was irradiated with 1.03, 19.3 and 249 MeV protons (linear
      energy transfer = 25.5, 2.7, and 0.39 keV microm(-1) respectively), 26 MeV helium
      nuclei (25.5 keV microm) and gamma-rays (137Cs or 60Co) in phosphate buffer
      containing 2 mM or 200 mM glycerol. Single-and double-strand breaks (SSB and DSB)
      were measured by gel electrophoresis, and clustered lesions containing base
      lesions were quantified by converting them into irreparable DSB in transformed
      bacteria. RESULTS: For protons, SSB yield decreased with increasing LET (linear
      energy transfer). The yield of DSB and all clustered lesions seemed to reach a
      minimum around 3 keV microm(-1). There was a higher yield of SSB, DSB and total
      clustered lesions for protons compared to helium nuclei at 25.5 keV microm(-1). A
      difference in the yields between 137Cs and 60Co gamma-rays was also observed,
      especially for SSB. CONCLUSION: In this work we have demonstrated the complex LET
      dependence of clustered-lesion yields, governed by interplay of the radical
      recombination and change in track structure. As expected, there was also a
      significant difference in clustered lesion yields between various radiation
      fields, having the same or similar LET values, but differing in nanometric track
      structure.

PMID- 15962763
TI  - Quantitative evaluation of the parameters of bacterial photoreactivation after
      exposure to ultraviolet light and ionizing radiation.
AB  - The purpose was to compare quantitatively the parameters of photoreactivation of
      an ultraviolet (UV) light hypersensitive strain of Escherichia coli Bs-1
      irradiated with UV light and ionizing radiation. In addition, to evaluate the
      influence of the different physical and chemical factors on the parameters of the
      photoreactivation kinetics of the bacterial cells exposed to ionizing radiation.
      Survival curves and kinetics of the photoreactivation were measured in E. coli Bs
      1 cells exposed to UV light (254 nm) and ionizing radiations (gamma-rays of
      137Cs, gamma-rays of 60Co and 25 MeV pulsed X-rays). A mathematical model
      describing the process of photoreactivation in terms of a decreasing effective
      dose was applied to the experimental data obtained here and that published by
      others to evaluate quantitatively the probability of photoreactivation and the
      irreversible component of the radiation damage. Both the rate and extent of
      photoreactivation decreased in the following order of inactivating agents: WUV
      light, pulsed X-ray beam, gamma-ray of 60Co and gamma-ray of 137Cs. However, the
      irreversible component of radiation damage increased with the same order of
      radiations whereas the probability of photoreactivation per unit time was
      independent of the kind of radiation. After exposure to 6 MeV photons, the
      parameters of photoreactivation were changed in the presence of caffeine or after
      irradiation in the presence of the radioprotective agent dithiothreitol. The
      independence of the probability of photoreactivation on the quality of radiation
      indicates the cells have the same ability to photoreactivate damage produced by
      different kinds of radiations and is an additional argument indicating that
      during ionizing radiation a UV-like damage can be produced. The decrease in the
      extent and the rate of photoreactivation with radiation quality is explained by
      the formation of irreversible damage rather than by the impairment of the
      photorecovery process itself. Chemical and physical factors influencing the
      relative contribution of ionization and excitation on the ionizing radiation
      effect could modify both the extent of the photoreactivation and the probability
      of the recovery per unit time. It is concluded that the mathematical approach
      used here may be useful to reveal some new relationships between the parameters
      of photoreactivation.

PMID- 15962764
TI  - Heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, potentiated
      radiation-induced cell killing in a hormone-sensitive prostate cancer cell line
      through degradation of the androgen receptor.
AB  - Until now, there has not been enough information on how androgens or androgen
      deprivation may influence the response of cancer cells to radiation. In this
      study, the effect of dihydrotestosterone (DHT) on cellular proliferative activity
      and radiosensitivity was examined in a hormone-sensitive human prostate cancer
      cell line, LNCaP. In addition, the study also examined how a heat shock protein
      90 (Hsp90) chaperone complex inhibitor modified the effect of DHT on the
      radiosensitivity of the cells, because binding of the androgen receptor (AR) to
      Hsp90 is required to maintain the stability and functioning of AR. The hormone
      sensitive human prostate cancer cell line, LNCaP, was used. Radicicol was used as
      one of the known Hsp90 chaperone complex inhibitors, and the cells were incubated
      in the presence of this compound at a concentration of 500 nM. Cellular
      radiosensitivity was determined by the clonogenic assay; the changes in the
      protein expression were examined by Western blotting or immunofluorescence. DHT
      at a concentration of 1 nM caused enhancement of the proliferative activity and
      reduction of the radiosensitivity of the cells. Radicicol at a concentration of
      500 nM abolished the DHT-induced decrease in cellular radiosensitivity and
      potentiated the radiation-induced cell killing synergistically. Consistent with
      the changes in the cellular radiosensitivity, radicicol degraded AR, Raf-1 and
      HER2/neu via reduced binding of AR to Hsp90, although selective degradation of
      HER2/neu caused by Herceptin, a monoclonal antibody against HER2, did not affect
      the cellular radiosensitivity. The results suggest that the Hsp9O chaperone
      complex may be a potential molecular target for potentiation of radiation-induced
      cell killing in a hormone-sensitive prostate cancer cell line.

PMID- 15962765
TI  - Critical volume model analysis of lung complication data from different strains
      of mice.
AB  - The critical volume (CV) normal tissue complication probability (NTCP) model was
      used to fit experimental data on radiation pneumonitis in mice to test the model
      and determine the values of the model parameters characterizing the lung
      structure: relative critical volume and cell radiosensitivity. The entire lungs
      of mice from ten different strains were irradiated acutely and homogeneously to
      different doses. The experimental animals from the different strains expressed
      different radiation sensitivities, forming ten well-defined dose-response curves.
      The most widely accepted biological NTCP model (the individual CV NTCP) readily
      applicable to cases of acute uniform irradiation was used to fit all the
      individual dose-response curves simultaneously. To account for the apparent
      difference in the response of the different strains, it was assumed that the
      strains differed in their (cell) radiosensitivity. The maximum likelihood method
      of fitting was used. The obtained fit was statistically highly acceptable. The
      best-fit value of the relative critical volume, mu, was 78%, which is extremely
      close to the histologically observed value of around 72%. The values of
      radiosensitivity, alpha, ranged between 0.26 and 0.37 Gy(-1) for the different
      strains. The best-fit numbers of functional subunits (FSU) constituting the lung,
      N, and the number of cells in an FSU, N(o), were implausibly low: N = 9 and N(o)
      = 23, respectively. The best-fit value of N(o)N was a very small number that was
      unlikely to correspond to the total number of cells comprising the lung,
      suggesting that a different interpretation of N and N(o) was required. The
      individual CV model provided a simultaneous description of the individual
      responses of different mouse strains through assumed interindividual variability
      in alpha only. A new interpretation is given to the entities corresponding to
      N(o) and N. N(o)N is interpreted as the number of certain elementary structures.
      These structures are considered to be equivalent to the classical functional
      subunit, which is much larger than a cell and plays a fundamental role in
      determining the radiation response of the organ. N is identified as the number of
      the few large subdivisions of the lungs, M = microN is the number that have to be
      damaged for the lung to fail. N(o) is interpreted as the mean number of
      elementary structures (FSU) per large subdivision. This imposes a picture of
      damage to large, contiguous subdivisions containing many FSU, which is consistent
      with the histological appearance of the lungs of mice in respiratory distress.
      This picture is in marked contrast to the random distribution of small areas of
      damage expected for the small size of an FSU. This random distribution is
      characteristic of earlier stages of the development of radiation pneumonitis,
      suggesting that some additional process spreads injury from damaged FSU to
      adjacent, undamaged FSU during the terminal phase.

PMID- 15962766
TI  - Ixodes philipi: redescription of female and first description of male, with
      records from streaked shearwater in Japan (Acarina: Ixodidae).
AB  - Ixodes philipi Keirans & Kohls, 1970 is so far known only from two female
      specimens taken from the streaked shearwater, Puffinus leucomelas (Temminck,
      1835) [presently Calonectris leucomelas (Temminck, 1835)], or the madeiran storm
      petrel, Oceanodroma castro (Harcourt, 1851), in Japan. We redescribe the female
      and describe the male of this species. We used nine adults (four males and five
      females) taken from the bodies of C. leucomelas and/or soil samples of their nest
      burrows in Japan, indicating that C. leucomelas is the main natural host bird of
      I. philipi.

PMID- 15962767
TI  - Optical and ultrastructural studies of midgut and salivary glands of first instar
      of Dermatobia hominis (Diptera: Oestridae).
AB  - Midguts and salivary glands of newly hatched larvae (L1) of Dermatobia hominis
      (L., Jr.) were studied using light and electron microscopy. The larval midgut has
      a tubular, sinusoidal form and consists of a monolayer of epithelial cells with
      an underlying basement membrane and a surrounding layer of connective tissue. The
      fine structure of the midgut shows digestive cells with short microvilli, large
      nuclei, and cytoplasm containing few visible organelles (mitochondria, rough
      endoplasmic reticulum, and free ribosomes). In the basal region, the plasma
      membrane of the cells is folded into a labyrinth area. Hemidesmosomes link the
      basal surface to the basement membrane and septet junctions are present between
      adjacent cells. The connective tissue circling the basement membrane contains
      collagen fibrils, muscle fibers, and tracheal tubes. Prominent nuclei with
      evident nucleoli occur in the digestive cells. The salivary gland is simple and
      tubular. It has a monolayer of epithelial cells surrounded by basement membrane
      and connective tissue. The fine structure of the salivary gland shows epithelial
      cells, microvilli, secretion into the lumen, septate junctions at the lateral
      face and a basal labyrinth region. The cell nucleus is large and the cytoplasm
      contains rough endoplasmic reticulum, ribosomes and mitochondria.

PMID- 15962768
TI  - Three new species and one new subspecies of Toxorhynchites (Diptera: Culicidae)
      of the afrotropical region.
AB  - Three new species and one new subspecies in the subgenus Afrorhynchus of the
      genus Toxorhynchites are described from the Afrotropical region. With the
      addition of these four new taxa, 14 species and two subspecies of subgenus
      Afrorhynchus are presently known in the region. Keys are provided for the
      identification of adult males and females of the subgenus Afrorhynchus in Africa.

PMID- 15962769
TI  - Larval morphology of Chrysomya nigripes (Diptera: Calliphoridae), a fly species
      of forensic importance.
AB  - The morphology of all instars of Chrysomya nigripes Aubertin, a blow fly species
      of forensic importance, is presented with the aid of both light microscopy and
      scanning electron microscopy (SEM). Morphological features of the
      cephalopharyngeal skeleton, anterior spiracle, posterior spiracle, and dorsal
      spines between the prothorax and mesothorax are highlighted. No consistent
      features were found, even using SEM, for distinguishing the first instar of C.
      nigripes from that of Chrysomya megacephala (F.) or Chrysomya rufifacies
      (Macquart), two other commonly associated blow fly species in corpses in
      Thailand. Several features observed in second and third instars proved to be
      valuable characteristics for separating these species.

PMID- 15962770
TI  - Anopheles gambiae s.l. and Anopheles funestus mosquito distributions at 30
      villages along the Kenyan coast.
AB  - This study investigated whether Anopheles gambiae s.l. and Anopheles funestus
      Giles mosquito populations were distributed randomly among houses on the coast of
      Kenya. Sample means and variances of mosquitoes were estimated from bimonthly
      pyrethrum spray collections at 30 villages from July 1997 through May 1998. In
      total, 5,476 An. gambiae s.l. and 3,461 An. funestus were collected. The number
      of An. gambiae s.l. collected was highest in November/December and lowest in May.
      The number of An. funestus collected was highest during September/October and
      lowest during May. As the density of mosquitoes decreased, there was a tendency
      toward randomness in the distribution. The proportion of An. gambiae s.l. and An.
      funestus mosquitoes collected per house for each sampling period also showed
      patterns of clustering, with 80% of An. gambiae s.l. collected from <30% of the
      houses and 80% of An. funestus collected from <20% of the total houses. The total
      number of mosquitoes collected from any one house ranged from 0 to 121 for An.
      gambiae s.l. and from 0 to 152 for An. funestus. This coupled with the results of
      the variance to mean ratio plots suggests extensive clustering in the
      distribution of An. gambiae s.l. and An. funestus mosquito populations throughout
      the year along the coast of Kenya.

PMID- 15962771
TI  - Genetic structure of the tick Ornithodoros coriaceus (Acari: Argasidae) in
      California, Nevada, and Oregon.
AB  - The argasid tick Ornithodoros coriaceus (Koch) is the only confirmed vector of
      epizootic bovine abortion (EBA) in the United States. The disease and its tick
      vector have historically been reported in the foothills of the Sierra Nevada
      Mountains and coast ranges of California. In the past two decades, the range of
      EBA has apparently expanded into southern Oregon and northern Nevada. Possible
      explanations for this expansion include 1) increased recognition and reporting of
      EBA in these regions; 2) widespread movement of tick-infested and EBA-infected
      hosts with subsequent colonization of these regions by infected ticks; and 3)
      widespread movement of the EBA agent, independent of tick movements, into extant
      tick populations in these new regions. The current study was performed to
      evaluate these hypotheses by examining patterns of variability in a 420-bp
      segment of the 16S mitochondrial rDNA gene sequence among 210 O. coriaceus
      individuals from 14 sites in California, Oregon, and Nevada. Sixty-three unique
      haplotypes were identified in the ticks tested, with 84% of the sequence
      variation attributable to among-population variation and 16% to within-population
      variation. A majority of the haplotypes were unique to their particular
      collection site, whereas only four collection sites shared haplotypes. Overall,
      very little evidence of gene flow among tick populations was detected, making it
      unlikely that widespread tick movement had introduced O. coriaceus and the EBA
      agent into new regions.

PMID- 15962773
TI  - Development of Dermatophagoides pteronyssinus (Acari: Pyroglyphidae) at constant
      and simultaneously fluctuating temperature and humidity conditions.
AB  - House dust mites are found in almost all dwellings in New Zealand and are a major
      risk factor in the development of asthma and perennial allergic rhinitis. We
      studied the longevity, life stage length, and fecundity of a New Zealand strain
      of European house dust mite, Dermatophagoides pteronyssinus (Trouessart), at
      constant (23 degrees C, 75% RH) and the fluctuating conditions typically found in
      dry (18-25 degrees C, 60-38% RH) and damp (18-23 degrees C, 70-55% RH) New
      Zealand dust mite microhabitats in carpets. All the adult mites placed in the
      "dry" conditions died within 18 d. Mites in the "da conditions had developmental
      times, oviposition, and death rates that were not significantly different from
      constant conditions. These mites are tolerant of fluctuating temperatures, but
      they are more susceptible to environments that strongly fluctuate in humidity.

PMID- 15962772
TI  - Fecundity of naturally blood-fed Ochlerotatus japonicus.
AB  - Ochlerotatus japonicus (Theobald) collected in gravid traps were held
      individually in modified BioQuip breeders in a darkened room under ambient
      conditions and readily oviposited on Styrofoam blocks. Counts were made of eggs
      laid on Styrofoam blocks, container sides, and water surface, and dissections
      allowed for counts of retained eggs to determine the fecundity of this species.
      In total, 32,970 eggs were oviposited by 289 females with a range of 3-249 eggs
      per female. The mean +/- SD number of eggs oviposited per female, 114.08 +/-
      51.08, was significantly less than the mean number of eggs produced per female,
      125.85 +/- 47.89. Wing lengths ranged from 2.8 to 4.7 mm with a mean of 3.81 +/-
      0.38 mm. Wing length was positively correlated with total eggs formed (r2 =
      0.3481); wing = 3.22054 + 0.0047 total eggs formed. There was no monthly size
      difference although females collected during October produced significantly fewer
      eggs than females collected from June to September. A low egg viability of 40%
      was attributed to improper storage of the Styrofoam blocks on which eggs were
      oviposited.

PMID- 15962774
TI  - Survivorship of Anopheles gambiae sensu stricto (Diptera: Culicidae) larvae in
      western Kenya highland forest.
AB  - The western Kenya highland has been experiencing dramatic landuse changes in the
      past three decades. Landuse change has been hypothesized to be one of the
      mechanisms for malaria epidemics in African highlands because it can alter the
      physical and chemical characteristics of mosquito breeding habitats. One
      important landuse change in western Kenya highland is deforestation. The current
      study examined the effects of forestation or deforestation on the survivorship of
      Anopheles gambiae larvae and colonization of other aquatic insects in larval
      habitats in Kakamega forest (elevation 1,500-1,700 m above sea level), western
      Kenya. We found that the survivorship of An. gambiae larvae was reduced from 55
      to 57% in habitats fully exposed to sunlight (open habitats) to 1-2% in habitats
      with full forest canopy coverage (forest habitats) and partial canopy coverage
      (forest edge habitats) in two out of three trials. The average daily water
      temperature of the open habitats was approximately 3-3.4 degrees C higher than
      the forest habitats. Insect species in the orders of Diptera, Coleoptera, and
      Odonata colonized the larval habitats, but the three habitat types differed
      greatly in the animal assemblage. Canonical correspondence analysis found that
      water temperature and amount of leaf litter were the significant variables
      associated with animal assemblages. Redundancy analysis revealed that openness
      and the presence of predatory animals were significantly related to An. gambiae
      survivorship. This result suggests that deforestation facilitates the survival of
      the immature stage of An. gambiae in the highland.

PMID- 15962775
TI  - Ecological characterization of the aquatic habitats of mosquitoes (Diptera:
      Culicidae) in enzootic foci of Venezuelan equine encephalitis virus in western
      Venezuela.
AB  - We studied the aquatic mosquito habitats in and around enzootic foci of
      Venezuelan Equine Encephalitis virus (VEE) in western Venezuela. Specimens were
      sampled for 5 mo in three types of vegetation: tall lowland tropical forests,
      short inundated/secondary growth forests, and pastures/herbaceous vegetation
      around forests. Ground pools, flooded pastures, swamps, ponds, and canals
      predominated. We used a multivariate statistical approach to quantitatively
      assess the relationships of mosquito species with broad categories of the
      landscape, and with environmental variables within each aquatic habitat. Twenty
      four mosquito species in the genera Aedes, Psorophora, Culex, Mansonia, and
      Uranotaenia were collected. Species richness was higher in the tall forests than
      in other types of vegetation. Discriminant Function Analysis showed a strong
      association between landscape category and mosquito species assemblage and
      identified Culex erraticus Dyar & Knab and Mansonia titillans Walker as indicator
      species of open areas, and Aedes serratus Theobald as an indicator of tall
      forests. M. titillans, Uranotaenia geometrica Theobald, Cx. erraticus, and Culex
      dunni Dyar were associated with unshaded, warm, vegetated waters in flooded
      pastures and swamps, whereas Ae. serratus, Aedes fulvus (Wiedemann), Psorophora
      albipes Theobald, Psorophora ferox (Humboldt), Culex caudelli Dyar & Knab, and
      Culex pedroi Sirivanakarn & Belkin were associated with small, shaded ground
      pools within the tall forests. Culex coronator Dyar & Knab was associated with
      partially exposed sites within short forests. These results allowed us to
      interpret better our previous studies on mosquito adult spread in the study area
      and their possible role as VEEV disseminators.

PMID- 15962776
TI  - Influence of meso- and microscale habitat structure on focal distribution of
      sympatric Ixodes scapularis and Amblyomma americanum (Acari: Ixodidae).
AB  - We compared the distribution of sympatric Ixodes scapularis Say and Amblyomma
      americanum (L.) within several suitable forested habitats at different spatial
      scales and characterized differences in microhabitat features accounting for the
      observed distribution of questing ticks. We used automatic data loggers placed in
      the shrub and litter layers to contrast mesoclimate and microclimate conditions
      experienced by questing ticks. Larger numbers of I. scapularis were collected at
      sites where the forest canopy was more fragmented and where the canopy contained
      more hardwood species than pitch pine, Pinus rigida Mill. Dominance of pine in
      the canopy affected the character of the shrub layer vegetation and composition
      of the litter layer, which concomitantly affected the microclimate conditions
      experienced by questing ticks. Pitch pine-dominated habitats were drier and
      hotter than those under a broad-leaved canopy, and questing ticks experienced
      increased saturation deficit in the later spring and summer in pine forest sites.
      The shrub layer vegetation seemed to have a moderating effect on the microclimate
      experienced by questing ticks and subtle differences in vegetation structure
      resulted in substantially different conditions as encountered by questing ticks
      over the space of a few meters. In contrast to questing I. scapularis, all three
      stages of questing A. americanum exhibited poor relationships with microclimate
      variables recorded in the litter and shrub layers. Further research is required
      to determine which environmental conditions and which habitats are most likely to
      support this species.

PMID- 15962777
TI  - Relationships between occurrence of Anopheles gambiae s.l. (Diptera: Culicidae)
      and size and stability of larval habitats.
AB  - One potentially important target of malaria vector control is the immature stages
      of anopheline mosquitoes. To design efficient larval control methods, mechanisms
      regulating mosquito productivity in natural habitats must be understood. We
      examined the relationships between pupal occurrence of Anopheles gambiae s.l. and
      size and stability of larval habitats for a period of 1 yr in western Kenya. We
      also examined relationships between abundance of indoor resting anophelines and
      habitat availability. Habitat size was measured by the total water volume (cubic
      meters). Habitat stability was defined as the number of occurrences when water
      was continuously present in a habitat for 6 d. Pupal occurrence was indicated by
      the number of days that pupae were observed in a habitat during the study period.
      We found that habitat stability and pupal occurrence were positively correlated
      with habitat size. When habitat size fell below approximately 1 m3, habitat
      stability and pupal occurrence decreased rapidly. Habitat availability was
      significantly correlated with the density of indoor resting mosquitoes in houses
      near to larval sites. These results suggest that habitat size is an important
      determinant of habitat stability, pupal occurrence, and adult mosquito abundance.

PMID- 15962778
TI  - Attraction of Culex pipiens/restuans (Diptera: Culicidae) mosquitoes to bird
      uropygial gland odors at two elevations in the Niagara region of Ontario.
AB  - In an effort to determine whether female Culex pipiens L. and Culex restuans
      Theobald mosquitoes (Diptera: Culicidae) are attracted to crow, Corvus
      brachyrhynchus, uropygial gland secretions, CDC miniature light traps (baited
      with CO2 but with the lights removed) were placed at approximately 1.5- and 5-m
      elevations, in 10 trees in awoodlot near Niagara Falls, Canada. These traps were
      assigned either a bird odor or a blank control. Bird odors were created by
      attaching cotton swabs coated with crow uropygial gland secretions to the trap
      intake. A significantly greater number of Cx. pipiens/ restuans were found in the
      5-m traps compared with 1.5-m traps, with a significant number attracted to the
      bird odor over the no odor traps at the 5-m elevation, but not at 1.5 m. We also
      found more Aedes vexans (Meigen) in the 1.5-m traps than the 5-m traps; however,
      presence or absence of bird odor did not influence the distribution of Ae.
      vexans.

PMID- 15962779
TI  - Comparison of contact and spatial repellency of catnip oil and N,N-diethyl-3
      methylbenzamide (deet) against mosquitoes.
AB  - Nepetalactone, the primary component of catnip oil, was compared with the
      repellent N,N-diethyl-3-methylbenzamide (deet) for its ability to affect the host
      seeking ability of Aedes aegypti (L.). A triple cage olfactometer was used to
      bioassay each substance and to assess its attraction inhibition (spatial
      repellent) attributes when combined with the following attractants: carbon
      dioxide, acetone, a blend of L-lactic acid and acetone, and human odors.
      Repellent tests were conducted with each substance against female Ae. aegypti,
      Anopheles albimanus Weidemann, and Anopheles quadrimaculatus Say. Catnip oil and
      deet were both weakly attractive to Ae. aegypti, catnip oil was the better
      spatial repellent, whereas deet was a more effective contact repellent in tests
      with all three species of mosquitoes.

PMID- 15962780
TI  - Comparative study on nocturnal behavior of Aedes aegypti and Aedes albopictus.
AB  - Nocturnal behavior of nonblood-fed females of Aedes aegypti (L.) and Aedes
      albopictus (Skuse) was studied using an automatic recording device equipped with
      a photoelectric sensor. Carbon dioxide, heating, and the contrast of the black
      and white colors were used as attractive cues for mosquitoes. The nocturnal host
      seeking activity positively correlated with the increasing light intensity in
      both species. Ae. aegypti was found to be more sensitive to light than Ae.
      albopictus. The threshold of light intensity for the activation of the nocturnal
      host-seeking activity was <0.1 lx (approximately 0.01 foot candle) in Ae. aegypti
      and >10 lx (approximately 1 foot candle) in Ae. albopictus. Complete darkness
      during the daytime deactivated the host-seeking activity of both species,
      irrespective of their increasing flight activity controlled by their intrinsic
      circadian rhythms. This finding suggested that visual cues are indispensable for
      host-seeking behavior. The eye parameter value, the product of the ommatidial
      diameter, and the interommatidial angle were significantly larger in Ae. aegypti
      than those in Ae. albopictus, indicating that the eye of Ae. aegypti is more
      adapted to a darker environment.

PMID- 15962781
TI  - Isozyme similarity in Anopheles oswaldoi sensu lato (Diptera: Culicidae) from the
      Amazon region, Brazil.
AB  - Isozyme electrophoresis studies were conduced on Anopheles oswaldoi sensu lato
      from three states in Amazonian (Brazil), including Acre, where this taxon has
      been incriminated as a potential human malaria vector. The 13 enzymes analyzed
      yielded a total of 20 loci. Of these, 10 were monomorphic in the three samples.
      Diagnostic loci were not found. The measures of genetic variability showed mean
      number of alleles per locus between 1.5 and 2.0, percentage of polymorphic loci
      of 40%, and mean heterozygosities from 0.031 to 0.062. The inbreeding coefficient
      F(IS) had a moderate mean value (0.109), which resulted from heterozygote
      genotype deficiencies and the presence of rare alleles in the homozygote state.
      Mean F(ST) value (0.0502) and genetic distance values (Nei's genetic similarity
      values of 0.994-0.997; Roger's genetic similarity values of 0.963-0.968) were
      very low among the three samples of An. oswaldoi s. l. Preliminary results of
      identifications of male genitalia indicated that An. oswaldoi s. s. Peryassu and
      Anopheles konderi Galvao & Damasceno of the An. oswaldoi complex coexist
      sympatrically in Sena Madureira, Acre, and Sao Miguel, Rondonia, whereas in the
      sample from Coari, Amazonas, only An. konderi was identified. The isozyme results
      do not suggest differences between these species, particularly in areas of
      sympatry.

PMID- 15962782
TI  - Seroprevalence of Oestrus ovis (Diptera, Oestridae) infestation and associated
      risk factors in ovine livestock from southwestern Spain.
AB  - This survey was carried out to determine the seroprevalence of nasal infestation
      by sheep bot fly, Oestrus ovis L., and to identify the risk factors associated
      with the disease in flocks in southwestern Spain. In total, 5,878 sera samples of
      adult sheep were collected at random in 551 farms from four provinces in the
      southwestern Spain: Badajoz, Caceres, Cordoba, and Sevilla. Sera were tested by
      enzyme-linked immunosorbent assay for O. ovis antibodies, by using a crude L2
      larval as antigen. The seropositive mean prevalence was 69.30%, and mean
      percentage of optical densities was 61.83%. There were significant differences
      between the provinces studied; C6rdoba and Sevilla were the provinces with more
      infested animals and higher seroprevalences. The correlation between
      seroprevalence and percentage of antibodies by farms was significant. There were
      only 18 farms free of seropositive animals, and 115 of the total 551 farms had
      all sampled animals seropositive, an indication of the high importance of this
      parasitosis in the investigated areas. Altitude, latitude, flock size, and ovine
      population density were the potential risk factors associated with the detection
      of O. ovis antibodies. Those animals breeding in regions located at low altitudes
      (<500 m), meridian latitudes (<39.5 degrees N), and on farms with medium-to-large
      flock size (>250 sheep) and high ovine population density (>100 sheep per km2)
      were more likely to be seropositive. These findings confirm that these studied
      factors should be considered as potential risk factors to the presence of O. ovis
      in ovines from southwestern Spain.

PMID- 15962783
TI  - Microbial control of Musca domestica (Diptera: Muscidae) with selected strains of
      Beauveria bassiana.
AB  - Nineteen strains and species of entomopathogenic fungi were examined for their
      potential as biological control agents of the house fly, Musca domestica L.
      Bioassays against larvae, pupae, and adult males and females in small containers
      indicated five strains of Beauveria bassiana (Bals.) Vuill. were relatively more
      virulent. Three of the virulent strains, chosen for efficiency of production in a
      rice-based, diphasic fungal production system, were further evaluated by mixing
      spore-contaminated rice residue with sugar and tested as a food bait for adult
      flies in a 33-m3 walk-in chamber. Up to 90% mortality was obtained within 15 d of
      exposure. The results indicate bait formulations of the most virulent and
      aggressive strain should be further developed and studied.

PMID- 15962784
TI  - Synthesis of additional endotoxins in Bacillus thuringiensis subsp. morrisoni PG
      14 and Bacillus thuringiensis subsp. jegathesan significantly improves their
      mosquitocidal efficacy.
AB  - A fundamental principal of resistance management is that the more complex and
      potent a toxin mixture, the slower resistance will develop to the mixture in an
      insect population. Thus, to develop more complex and potent mosquitocidal
      bacteria, we genetically engineered Bacillus thuringiensis subsp. morrisoni PG-14
      and Bacillus thuringiensis subsp. jegathesan, to synthesize, respectively, the
      binary (Bin) toxin of Bacillus sphaericus or a combination of Bin and the CytlA
      protein of Bacillus thuringiensis subsp. israelensis. Engineering these two
      larvicidal bacteria in general significantly improved their efficacy against
      fourth instars in comparison with their wild-type parental strains. For B.
      thuringiensis subsp. morrisoni PG-14, which naturally synthesizes Cyt1A,
      synthesis of Bin improved efficacy nine-fold (LC50 from 4.5 to 0.5 ng/ml) against
      Culex quinquefasciatus Say, although no improvement was observed (LC50 of 2 ng/ml
      for both strains) against Aedes aegypti L. For B. thuringiensis subsp.
      jegathesan, cosynthesis of Bin plus Cyt1A in combination with its normal
      complement of endotoxins improved efficacy 17-fold (LC50 from 34 to 2 ng/ml)
      against Cx. quinquefasciatus and 3.2-fold (LC50 from 68 to 21 ng/ml) against Ae.
      aegypti. Addition of Bin alone to B. thuringiensis subsp. jegathesan did not
      improve toxicity (LC50 from 68 to 65 ng/ml) against Ae. aegypti, indicating that
      CytlA synergized the activity of the endotoxins in this strain against Ae.
      aegypti. These results demonstrate that mosquitocidal efficacy of these strains
      and likely their resistance management properties can be improved significantly
      by increasing their toxin complexity and the amount of toxin they synthesize.

PMID- 15962785
TI  - Increased monooxygenase activity associated with resistance to permethrin in
      Pediculus humanus capitis (Anoplura: Pediculidae) from Argentina.
AB  - We studied the profile of permethrin resistance in populations of head lice
      infesting children 6-12 yr old in schools and their homes in and around Buenos
      Aires, Argentina. Five permethrin-resistant populations with different levels of
      resistance were collected: Hogar Loyola (HL), Republica de Turquia (RT), Hogar
      Mitre (HM), Guardia de Honor (GH), and Ricardo Guiraldes (RG). One susceptible
      population, Bandera Argentina (BA), also was collected. Their level of resistance
      was evaluated, and results showed resistance ratios of 13 for HL, 16 for RT, 22
      for HM, 61 for GH, and 69 for RG. To elucidate the possible involvement of the
      cytochrome P450 monooxygenase system in conferring permethrin resistance,
      ethoxycoumarin-O-deethylase (ECOD) activity was measured in abdomens of
      individual third instars and adults by using a fluorometric assay. The ECOD
      activity was lower in the susceptible BA population (4.7 ng per louse) than in
      the resistant ones (13.7 ng per louse for RG, 12.3 ng per louse for GH, 8.6 ng
      per louse for RT, and 8.2 ng per louse for HL). ECOD activity was significantly
      correlated with the level of resistance in the field populations (r = 0.97, P =
      0.0009), suggesting a role for cytochrome monooxygenase P450 system in permethrin
      resistance by head louse, Pediculus humanus capitis De Geer.

PMID- 15962786
TI  - Oxalic acid as a fungal acaracidal virulence factor.
AB  - Cell-free culture supernatants of the entomopathogenic fungus Beauveria bassiana
      (Bals.) Vuillemin were able to induce mortality in several tick species,
      including adult Ambylomma americanum (L.), Ambylomma maculatum Koch, and Ixodes
      scapularis Say. Four lines of experimental evidence support the hypothesis that
      oxalic acid secretion by B. bassiana, coupled to a reduction in the pH of the
      medium, act as potent acaricidal factors during pathogenesis. 1) Acaracidal
      activity of culture supernatants was retained after treatments including boiling
      and protease digestion, but was lost after dialysis. 2) Metabolite analyses
      indicated oxalate to be the major secreted organic compound present in the active
      culture supernatants. 3) Treatment of ticks with the pure compound oxalate at pH
      4.0 resulted in almost 80% mortality in adult A. americanum ticks within 14 d,
      whereas treatment of ticks with oxalate at pH 7.0, or with formate, citrate, or
      phosphate at both pH 4 and 7 resulted in <10% mortality, even after 28 d. 4) Cell
      free culture supernatants from B. bassiana mutants with decreased oxalate
      production displayed lower acaricide activity than wild type.

PMID- 15962787
TI  - Use of novel compounds for pest control: insecticidal and acaricidal activity of
      essential oil components from heartwood of Alaska yellow cedar.
AB  - Laboratory bioassays were conducted to determine the activity of 15 natural
      products isolated from essential oil components extracted from the heartwood of
      Alaska yellow cedar, Chamaecyparis nootkatensis (D. Don) Spach., against Ixodes
      scapularis Say nymphs, Xenopsylla cheopis (Rothchild), and Aedes aegypti (L.)
      adults. Four of the compounds from the essential oil have been identified as
      monoterpenes, five as eremophilane sesquiterpenes, five as eremophilane
      sesquiterpene derivatives from valencene and nootkatone, and one as a
      sesquiterpene outside the eremophilane parent group. Carvacrol was the only
      monoterpene that demonstrated biocidal activity against ticks, fleas, and
      mosquitoes with LC50 values after 24 h of 0.0068, 0.0059, and 0.0051% (wt:vol),
      respectively. Nootkatone from Alaska yellow cedar was the most effective of the
      eremophilane sesquiterpenes against ticks (LC50 = 0.0029%), whereas the
      nootkatone grapefruit extract exhibited the greatest biocidal activity against
      fleas (LC50 = 0.0029%). Mosquitoes were most susceptible to one of the
      derivatives of valencene, valencene-13-aldehyde (LC50 = 0.0024%), after 24 h.
      Bioassays to determine residual activity of the most effective products were
      conducted at 1, 2, 4, and 6 wk after initial treatment. Residual LC50 values for
      nootkatone did not differ significantly at 4 wk posttreatment from the
      observations made at the initial 24-h treatment. The ability of these natural
      products to kill arthropods at relatively low concentrations represents an
      alternative to the use of synthetic pesticides for control of disease vectors.

PMID- 15962788
TI  - The Fc fragment mediates the uptake of immunoglobulin C from the midgut to
      hemolymph in the ixodid tick Amblyomma americanum (Acari: Ixodidae).
AB  - The phenomenon of immunoglobulin uptake from the midgut into the hemolymph has
      been observed in both argasid and ixodid ticks, but the mechanism of the uptake
      is not known. Using capillary feeding of adult Amblyomma americanum (L.) female
      ticks, we investigated the role of immunoglobulin G Fc and Fab fragments in the
      uptake process. Intact IgG and fragments labeled with 125I were introduced alone
      or as a mixture with a 10-fold molar excess of unlabeled compounds into ticks,
      and then the concentration of the compounds after 3 and 6 h of continuous feeding
      was assessed in the hemolymph. Our results showed that the uptake of Fc fragments
      was approximately 4 times higher than Fab fragments at 6 h of the feeding and
      that Fc but not Fab fragments competed with uptake of intact IgG. Glycosylation
      of the immunoglobulins did not seem to be required for uptake. There was not a
      statistically significant difference between the uptake of untreated IgG and IgG
      treated either with periodate or N-glycanase, and untreated Fc fragments or
      deglycosylated Fc fragments had equal activity in competition experiments with
      IgG. The uptake into hemolymph of IgG and Fc fragments, but not Fab fragments,
      was dependent on the pH of the feeding solution and showed a maximum at
      approximately pH 7.0. In addition, tick midgut cells bound Fc fragments with high
      affinity, estimated at 21 nM; the interaction with Fab fragments seemed
      nonspecific. Our results suggest that Fc fragments are the major determinant for
      the specific uptake of immunoglobulin G into tick hemolymph.

PMID- 15962789
TI  - Avian host and mosquito (Diptera: Culicidae) vector competence determine the
      efficiency of West Nile and St. Louis encephalitis virus transmission.
AB  - The ability of the invading NY99 strain of West Nile virus (WNV) to elicit an
      elevated viremia response in California passerine birds was critical for the
      effective infection of Culex mosquitoes. Of the bird species tested, Western
      scrub jays, Aphelocoma coerulescens, produced the highest viremia response,
      followed by house finches, Carpodacus mexicanus, and house sparrows, Passer
      domesticus. Most likely, few mourning, Zenaidura macroura, or common ground,
      Columbina passerine, doves and no California quail, Callipepla californica, or
      chickens would infect blood-feeding Culex mosquitoes. All Western scrub jays and
      most house finches succumbed to infection. All avian hosts produced a lower
      viremia response and survived after infection with an endemic strain of St. Louis
      encephalitis virus. Culex species varied in their susceptibility to infection
      with both viruses, with Culex stigmatosoma Dyar generally most susceptible,
      followed by Culex tarsalis Coquillett, and then Culex p. quinquefasciatus Say.
      Populations within Culex species varied markedly in their susceptibility, perhaps
      contributing to the focality of WNV amplification. Transmitting female Cx.
      tarsalis expectorated from six to 3,777 plaque-forming units (PFU) of WNV during
      transmission trials, thereby exposing avian hosts to a wide range of infectious
      doses. Highly susceptible house finches and moderately susceptible mourning doves
      were infected by subcutaneous inoculation with decreasing concentrations of WNV
      ranging from 15,800 to <0.3 PFU. All birds became infected and produced
      comparable peak viremias on days 2-3 postinoculation; however, the rise in
      viremia titer and onset of the acute phase of infection occurred earliest in
      birds inoculated with the highest doses. WNV virulence in birds seemed critical
      in establishing elevated viremias necessary to efficiently infect blood feeding
      Culex mosquitoes.

PMID- 15962790
TI  - Prefeeding Dermacentor andersoni (Acari: Ixodidae) on cattle with prior tick
      exposure may inhibit detection of tick paralysis by using hamster bioassay.
AB  - The effect of prefeeding Dermacentor andersoni Stiles on naive and previously
      challenged cattle before conducting virulence assays by using hamsters was
      examined. In an initial observational trial, ticks prefed on a previously
      challenged heifer did not cause paralysis after transfer to hamsters, whereas
      ticks from the same lot that were prefed on a naive heifer did cause paralysis.
      Subsequent paired trails were conducted to simultaneously compare paralysis after
      feeding on naive and previously challenged heifers. In the first trial,
      prefeeding ticks on a previously challenged heifer did not result in loss of
      virulence. In a second trial, ticks fed on a previously challenged heifer had
      greatly diminished virulence after transfer to hamsters. This also occurred in a
      third trial after the previously challenged animal had two prior exposures to
      virulent D. andersoni. Weight gains of ticks that did not cause paralysis after
      transfer to hamsters were higher after feeding on previously challenged cattle,
      indicating that loss of virulence was not due to failure of ticks to reattach and
      feed. Ticks gained little weight on paralyzed hamsters due to the reduced time
      spent feeding on hamsters when paralysis occurred. Results indicate that assaying
      ticks for virulence requires prefeeding on naive hosts. If these are not
      available, rabbits, a resistant host, can be used for prefeeding ticks.

PMID- 15962791
TI  - Failure of ticks to transmit Scopulariopsis brevicaulis (Deuteromycota), a common
      filamentous fungal commensal of ticks.
AB  - The capacity of ticks to transmit a fungus was examined by analyzing tick saliva,
      host tissue from feeding sites, and host blood for presence of Scopulariopsis
      brevicaulis (Sacc.) Bainier, an internal mycosymbiont of the American dog tick,
      Dermacentor variabilis (Say), and lone star tick, Amnblyomma americanum (L.).
      Although >85% of ticks were infected with S. brevicaulis, conidia presence was
      low (0-5% of samples) in microscopic observations and mycological culturing of
      saliva expressed from larvae, nymphs, and adults. Additionally, the recovery of
      S. brevicaulis from blood and tissue feeding sites from a rabbit where S.
      brevicaulis-positive adult ticks had attached and fed was not increased compared
      with control tissue where no feeding occurred, indicating that transmission does
      not occur by the blood-feeding route. Tick mouthparts were found to contain S.
      brevicaulis in addition to Penicillium glabrum (Wehmer) Westling, but these
      agents were sparse in isolations from the feeding sites, which makes it unlikely
      that ticks act frequently as a mechanical fungal vector.

PMID- 15962792
TI  - Western gray squirrel (Rodentia: Sciuridae): a primary reservoir host of Borrelia
      burgdorferi in Californian oak woodlands?
AB  - In California, dense woodlands have been recognized as important biotopes where
      humans are exposed to the nymphal stage of the western blacklegged tick, Ixodes
      pacificus Cooley & Kohls, the primary vector of the Lyme disease spirochete
      Borrelia burgdorferi sensu stricto (s.s.), in the far-western United States. To
      identify the principal reservoir host(s) of this spirochete, and of closely
      related spirochetes in the B. burgdorferi sensu lato (s.l.) complex, in dense
      woodlands in Mendocino County, California, approximately 50 species of birds and
      mammals, including wood rats and kangaroo rats, were evaluated as potential hosts
      for vector ticks and borreliae in 2002 and 2003. Although polymerase chain
      reaction (PCR) and sequencing analyses revealed that many vertebrate species had
      been exposed to one or more members of the B. burgdorferi s.l. spirochetal
      complex, only the western gray squirrel, Sciurus griseus, fulfilled the major
      criteria for a reservoir host of B. burgdorferi s.s. Ear-punch biopsies from
      eight of 10 squirrels collected from five separate woodlands were PCR-positive
      for B. burgdorferi s.s., 47% of I. pacificus larvae (n = 64) and 31% of nymphs (n
      = 49) removed from squirrels contained B. burgdorferi s.l., and the engorgement
      status of I. pacificus larvae was associated positively with acquisition of
      spirochetes. Overall, 83 and 100% of the amplicons sequenced from PCR-positive I.
      pacificus larvae and nymphs, respectively, were identified as B. burgdorferi s.s,
      Among the five remaining positive I. pacificus larvae, three contained B.
      bissettii and two had uncharacterized B. burgdorferi s.l. Borrelia burgdorferi
      s.s. was detected in one of five larvae and zero of two nymphs of the Pacific
      Coast tick, Dermacentor occidentalis Marx, that likewise had been removed from
      squirrels. The rickettsial agent of human anaplasmosis, Anaplasma
      phagocytophilum, was detected in the blood or ear biopsies of two squirrels and
      in one (1.6%) of 64 I. pacificus larvae and two (4.1%) of 49 nymphs obtained from
      squirrels. The one rickettsial-positive larva was coinfected with B. burgdorferi
      s.s. The apparently high reservoir potential of S. griseus for B. burgdorferi
      s.s., plus the fact that the geographic distribution of this squirrel coincides
      well with that of most reported human cases of Lyme disease in this region,
      indicated that it may be essential for maintaining foci of B. burgdorferi s.s. in
      certain types of woodlands. The findings with respect to A. phagocytophilum,
      although of less certain significance, suggest that S. griseus could serve as a
      secondary host of this rickettsia.

PMID- 15962793
TI  - Retention of Escherichia coli by house fly and stable fly (Diptera: Muscidae)
      during pupal metamorphosis and eclosion.
AB  - Populations of Escherichia coli obtained by feeding larval house flies, Musca
      domestica L. and stable flies, Stomoxys calcitrans (L.), persisted through the
      pupal stage. The abundance of E. coli in house fly pupae increased initially then
      declined before adult emergence. Abundance of E. coli in stable fly pupae
      increased through pupal development and remained high. Infected stable fly pupal
      cases typically contained more E. coli than house fly pupal cases. A greater
      proportion of emerging adult house flies were infected with E. coli compared with
      stable flies; however, the abundance of E. coli on infected flies was similar
      between species. Adult flies contained 0.04-0.19% of the E. coli in the pupal
      cases. The proportion of infected house fly adults and the amount of E. coli on
      the infected flies were related to the levels of E. coli in the pupal cases;
      however, these relationships did not occur with the stable fly. Results suggest
      that retention of E. coli from larval to adult house flies could play a role in
      the transmission and spread of E. coli, whereas stable fly adults probably play a
      minor role in E. coli spread. However, pupae of both species have potential to
      act as reservoirs for E. coli.

PMID- 15962794
TI  - Transmission of a Venezuelan equine encephalitis complex Alphavirus by Culex
      (Melanoconion) gnomatos (Diptera: Culicidae) in northeastern Peru.
AB  - Venezuelan equine encephalitis (VEE) complex alphaviruses are serious health
      threats in the Americas and regularly infect humans living in or near Amazonian
      rain forests. As part of a larger surveillance program, we placed six hamster
      baited mosquito traps in a disturbed white sand forest of northeastern Peru for 3
      d. Virus isolations from hamster serum and trapped mosquito pools demonstrated
      that a VEE subtype IIIC alphavirus was transmitted to a hamster by the mosquito
      Culex (Melanoconion) gnomatos Sallum, Hutchings & Ferreira. This species, like
      the other seven proven VEE complex alphavirus vectors, is a member of the
      Spissipes section of this subgenus. The composition of mosquitoes collected at
      the site over the sampling period was typical for the region.

PMID- 15962795
TI  - Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae) for
      vesicular stomatitis virus.
AB  - To determine the vector competence of Culicoides sonorensis Wirth & Jones midges
      for vesicular stomatitis virus (VSV)-New Jersey, insects were experimentally
      infected per os and sampled over time. Viral replication, as determined by in
      situ hybridization, was seen in epithelial, neural, and hemolymph cell types
      throughout the insect. Spatial and temporal distribution of virus was determined
      by immunohistochemical examination of sequentially sampled insects. Tissues of
      the alimentary canal were infected in a temporal pattern that paralleled the
      route of digestion/absorption: foregut and midgut by day 1, surrounding hemolymph
      and Malpighian tubules by day 3, and finally the midgut/ hindgut junction,
      hindgut, and rectal region by day 5. The circulation of virus in the hemolymph by
      day 3 coincided with infection of the dermis and fat bodies, the salivary glands,
      eyes, cerebral and subthoracic ganglia, and the ovaries. Oviduct epithelium and
      ovarial sheaths were infected by day 3, followed by infection of the developing
      oocytes by day 5. Interestingly, neural infections were seen in the subabdominal
      ganglia innervating the midgut in 33% of insects by 1 d postfeeding in the
      absence of positive staining in the hemolymph or surrounding tissues. A
      retrograde axonal transport infection route for these ganglia is discussed. The
      disseminated, productive, noncytolytic infection in Culicoides is consistent with
      that of an efficient biological vector for VSV. Virus readily replicated
      throughout the insect, passing both midgut and salivary gland infection barriers
      and reaching transmission-related organs in 3 d. Establishing the competence of
      this insect vector for VSV provides the foundation for animal transmission
      studies in the future. The possibility of horizontal, transovarial, and
      mechanical transmission is discussed.

PMID- 15962796
TI  - Bioecology and vectorial capacity of Aedes albopictus (Diptera: Culicidae) in
      Macao, China, in relation to dengue virus transmission.
AB  - Until 2001, the Chinese Territory of Macao had not registered any autochthonous
      dengue cases, despite the abundance of Aedes albopictus (Skuse), a known vector.
      This work describes a bioecological characterization of the local Ae. albopictus
      adult population, with the purpose of estimating the receptivity of Macao to
      dengue introduction. In the wet seasons of 1997 and 1998 and the dry season of
      1998, Ae. albopictus was the most abundant human-biting mosquito. Daily biting
      rates of 314 mosquitoes per person were recorded in the wet season with a
      reduction to 94 in the dry season. Ae. albopictus was mainly exophagic and
      exophilic and had a human blood index of 44%. The parity rate of field-collected
      mosquitoes was 57%. Daily survival rate ranged from 91 to 97%. Estimates of
      vectorial capacity ranged from 144 to 880, depending on what parameter values
      were used. These estimates indicated a great receptivity for the introduction of
      dengue viruses, as the 2001 outbreak came to prove.

PMID- 15962797
TI  - Ultrastructural study of West Nile virus pathogenesis in Culex pipiens
      quinquefasciatus (Diptera: Culicidae).
AB  - The ultrastructural features of West Nile virus (WNV) replication and
      dissemination in orally infected Culex pipiens quinquefasciatus Say were analyzed
      over a 25-d infection period. To investigate the effects of virus replication on
      membrane induction, cellular organization, and cell viability in midgut and
      salivary gland tissues, midguts were dissected on days 3, 7, 14, and 21, and
      salivary glands were collected on days 7, 14, 21, and 25 postinfection (d.p.i.)
      for examination by transmission electron microscopy (TEM). Whole mosquito heads
      were embedded for TEM analysis 14 d.p.i. to localize WNV particles and to
      investigate the effects of replication on nervous tissues of the brain. Membrane
      proliferation was induced by WNV in the midgut epithelium, midgut muscles, and
      salivary glands, although extensive endoplasmic reticulum swelling was a unique
      feature of salivary gland infection. TEM revealed WNV-induced pathology in
      salivary glands at 14, 21, and 25 d.p.i., and we hypothesize that long-term virus
      infection of this tissue results in severe cellular degeneration and apoptotic
      like cell death. This finding indicates that the efficiency of WNV transmission
      may decrease with mosquito age postinfection.

PMID- 15962798
TI  - Reservoir competence of native North American birds for the lyme disease
      spirochete, Borrelia burgdorfieri.
AB  - Reservoir competence for the Lyme disease spirochete, Borrelia burgdorferi, was
      tested for six species of native North American birds: American robin, gray
      catbird, brown thrasher, eastern towhee, song sparrow, and northern cardinal.
      Wild birds collected by mist netting on Fire Island, NY, were held in a field
      laboratory in cages over water and locally collected larval ticks were placed on
      the birds, harvested from the water after engorgement, and tested for infection
      by direct fluorescentantibody staining after molting to the nymphal stage.
      American robins were competent reservoirs, infecting 16.1% of larvae applied to
      wild-caught birds, compared with 0% of control ticks placed on uninfected
      laboratory mice. Robins that were previously infected in the laboratory by
      nymphal feeding infected 81.8% of applied larvae. Wild-caught song sparrows
      infected 4.8% of applied larvae and 21.1% when infected by nymphal feeding.
      Results suggest moderate levels of reservoir competence for northern cardinals,
      lower levels for gray catbirds, and little evidence of reservoir competence for
      eastern towhees or brown thrashers. Lower infection rates in larvae applied to
      wild-caught birds compared with birds infected in the laboratory suggest that
      infected birds display temporal variability in infectiousness to larval ticks.
      Engorged larvae drop from birds abundantly during daylight, so the abundance of
      these bird species in the peridomestic environment suggests that they might
      contribute infected ticks to lawns and gardens.

PMID- 15962799
TI  - Relative encounter frequencies and prevalence of selected Borrelia, Ehrlichia,
      and Anaplasma infections in Amblyomma americanum and Ixodes scapularis (Acari:
      Ixodidae) ticks from central New Jersey.
AB  - To evaluate their relative importance in tick-borne disease transmission in New
      Jersey, host-seeking Amblyomma americanum (L.) and Ixodes scapularis Say adults
      and nymphs were collected during spring activity periods in 2003 and 2004 to
      determine relative frequencies at which these ticks were encountered from an area
      known to be hyperendemic for Lyme disease. Although similar numbers of the two
      species were encountered during early spring of both years, A. americanum were
      encountered more often later in the season and exhibited a longer activity period
      than I. scapularis. A. americanum nymphs were collected at frequencies between
      2.6 and 7.3 times higher than I. scapularis nymphs. Polymerase chain reaction
      (PCR) analysis of 121 A. americanum adults yielded infection prevalences of 9.1%
      for Borrelia lonestari, 12.3% for Ehrlichia chaffeenensis, and 8.2% for E.
      ewingii, and coinfection prevalences of 4.1% for E. chaffeensis/E. ewingii and
      0.8% for E. chaffeensis/B. lonestari. Infection prevalences in 147 I. scapularis
      adults were 50.3% for B. burgdorferi, 6.1% for Anaplasma (Ehrlichia)
      phagocytophilum, and 1.4% for a recently described novel Borrelia species,
      whereas the coinfection prevalences were 2.7% for B. burgdorferi/A.
      phagocytophilum, 0.7% for B. burgdorferi/novel Borrelia, and 0.7% for A.
      phagocytophilum/novel Borrelia. The B. burgdorferi infection prevalence in I.
      scapularis was considerably higher than that in A. americanum. However, the
      higher A. americanum encounter frequencies compared with I. scapularis may result
      in increased risk of acquiring exposure to A. americanum-transmitted pathogens.
      The potential public health implications of these results are discussed.

PMID- 15962800
TI  - Presence of Borrelia burgdorferi (Spirochaetales: Spirochaetaceae) in southern
      Kettle Moraine State Forest, Wisconsin, and characterization of strain W97F51.
AB  - Lyme disease, caused by Borrelia burgdorferi Johnson, Schmidt, Hyde, Steigerwalt
      & Brenner; babesiosis, caused by Babesia microti Franca; and human granulocytic
      ehrlichiosis, caused by Anaplasma phagocytophilum Bakken & Dumler have been
      reported in Wisconsin, mainly in the endemic areas of the northwestern part of
      the state. People exposed to blacklegged ticks, Ixodes scapularis Say, from this
      region can potentially contract one or all of these diseases concurrently. Within
      the past several years, there have been cases of Lyme disease reported from
      southeastern Wisconsin, an area that contains deer, mice, and similar vegetation
      found at regions with high endemicity. However, past white-tailed deer surveys
      suggested no existence of I. scapularis in southeastern Wisconsin. However, in
      1996, we identified questing adult I. scapularis in the southernmost part of the
      Southern Kettle Moraine State Forest, Walworth County. To determine whether an
      established population of I. scapularis exists in this region, we performed a
      detailed survey of the abundance of host-seeking I. scapularis adults and the
      presence and abundance of subadults feeding on white-footed mice, Peromyscus
      leucopus Rafinesque. We also tested for possible infections of B. burgdorferi,
      Ba. microti, and A. phagocytophilum in ticks and B. burgdorferi harbored by mice.
      In 1997 and 1998, a total of 249 P. leucopus mice and 118 questing adult I.
      scapularis ticks, in addition to 157 larvae and seven nymphs feeding on mice,
      were collected and their locations were recorded from the Nordic trails of the
      Southern Kettle Moraine State Forest. Only one P. leucopus and its attached
      engorged I. scapularis nymph were infected with B. burgdorferi, whereas none of
      the engorged larvae attached to mice were infected. However, 4.2% of questing
      adult I. scapularis were infected with B. burgdorferi. The abundance of questing
      adult I. scapularis was 1.6 ticks per hour. The prevalence of subadult ticks on
      mice was 27%, with a mean intensity on infested mice of 2.0. I. scapularis adults
      were not infected with either Ba. microti or A. phagocytophilum. A unique strain
      of B. burgdorferi s.l. (W97F51) was discovered, showing 33 nucleotide
      substitutions and one codon insertion in a 567-bp fragment of the OspB gene,
      compared with Borrelia bissettii (strain Ca389). The sequences of ospA, ospB,
      ospC,fla, and rrs genes and the rrf-rrl intergenic spacer region were compared
      between W97F51 and other B. burgdorferi s.l. species. Although W97F51 was most
      genetically related to B. bissettii, the genetic identity of W97F51 was less than
      that of B. bissettii conspecifics. This study documents the existence of an
      established population of I. scapularis and the presence of B. burgdorferi with a
      novel strain in southeastern Wisconsin.

PMID- 15962801
TI  - Detection of Rickettsia, Borrelia, and Bartonella in Carios kelleyi (Acari:
      Argasidae).
AB  - Carios kelleyi (Colley & Kohls 1941), a tick associated with bats and bat
      habitats, has been reported to feed on humans, but there is little published data
      regarding the presence of vector-borne pathogens in these ticks. C. kelleyi
      nymphs and adults were collected from residential and community buildings in
      Jackson County, Iowa, and tested by polymerase chain reaction for Rickettsia,
      Borrelia, Bartonella, Coxiella, and Anaplasma. Rickettsia DNA was detected in 28
      of 31 live ticks. Sequences of the 17-kDa and rOmpA genes suggest that this agent
      is a novel spotted fever group Rickettsia. Transstadial and transovarial
      transmission of this Rickettsia were demonstrated. The flagellin gene of a
      Borrelia, closely related to B. turicatae, was detected in one of 31 live ticks.
      The 16S-23S intergenic spacer region of Bartonella henselae also was detected in
      one of 31 live ticks. Coxiella or A. phagocytophilum DNA were not detected in
      these ticks.

PMID- 15962802
TI  - Effects of antemortem ingestion of ethanol on insect successional patterns and
      development of Phormia regina (Diptera: Calliphoridae).
AB  - The effects of antemortem ingestion of ethanol by domestic pigs, Sus scrofa L.,
      on postmortem insect successional patterns and the development of Phormia regina
      (Meigen) were studied during summer 2003 in Blacksburg, VA. Insect samples were
      collected from the carcasses of ethanol-treated and untreated pigs for 10 d
      postmortem during two successional studies. In total, 32 insect taxa were
      collected during the two studies, with 29 and 27 taxa observed on the carcasses
      of ethanol-treated and untreated pigs, respectively. The earliest arrivers to
      both carcass types were dipterans. This group was represented by six families,
      with P. regina and Phaenicia coeruleiviridis (Macquart) being the most common
      calliphorids. Beetles in six families were collected on the carcasses of ethanol
      treated pigs, but only three of the families were collected on carcasses of the
      untreated pigs. Permutation analyses to test the null hypothesis of no similarity
      between successional patterns of insect taxa from carcasses of ethanol-treated
      and untreated pigs showed that the successional patterns were similar between
      carcass types in the first (P = 0.003) and the second (P = 0.01) studies. The
      results of the development study of P. regina maggots in the field show that
      there was a significant difference between the distributions of length for
      maggots reared on loin tissue from ethanol-treated and untreated pigs. Maggots
      that fed on tissue from ethanol-treated pigs took approximately 11.9 h longer to
      reach the pupal stage than maggots that fed on tissue from untreated pigs. The
      longer developmental time for maggots on tissue from ethanol-treated pigs was due
      mainly to the longer postfeeding period of the third instar.

PMID- 15962803
TI  - Detection of West Nile viral RNA from an overwintering pool of Culex pipens
      pipiens (Diptera: Culicidae) in New Jersey, 2003.
AB  - In total, 1,324 Culex pipiens pipiens L. female mosquitoes were collected at Ft.
      Hancock, Monmouth County, New Jersey, from January to March 2001-2003. Mosquitoes
      were held in an insectary at 27 degrees C and a photoperiod of 16:8 (L:D) h for 6
      to 21 d after which they were tested in 34 pools. West Nile viral RNA was
      detected in one pool by a TaqMan reverse transcription-polymerase chain reaction
      assay; however, infectious virus could not be isolated using either Vero cell
      plaque assay or C6/36 mosquito cells. Twenty females dissected in January and
      March 2003 confirmed ovarian diapause status. We suggest that the mode of
      infection in this pool of overwintering females may have been due to vertical
      (transgenerational) transmission.

PMID- 15962804
TI  - Detection of chandipura virus from sand flies in the genus Sergentomyia (Diptera:
      Phlebotomidae) at Karimnagar District, Andhra Pradesh, India.
AB  - A total of 191 adult sand flies belonging to the genus Sergentomyia were
      collected from seven villages in Karimnagar and Warangal districts of Andhra
      Pradesh State, India, after an outbreak of encephalitis due to Chandipura virus
      (CHPV). Fifteen pools, each containing two specimens, were tested by reverse
      transcriptase-polymerase chain reaction and sequencing. One pool of Sergentomyia
      from Kolanur village in Karimnagar District was positive for CHPV.

PMID- 15962805
TI  - First record of hosts for tick Carios kelleyi (Acari: Ixodida: Argasidae) in
      Canada and Montana.
AB  - I found Carios kelleyi Cooley & Kohls (formerly Ornithodoros kelleyi) (Acari:
      Ixodida: Argasidae) on five species of bats (Eptesicusfuscus, Myotis lucifugus,
      Myotis ciliolabrum, Myotis evotis, and Myotis volans) in the prairies of
      southeastern Alberta and north central Montana. This is the first occurrence of
      ticks on bats in Canada. This is also the first record of C. kelleyi on M. evotis
      and M. volans. Dates of parasitization ranged from 22 May to 17 October, and the
      number of ticks per host ranged from 1 to 44 (median two ticks per host). Number
      of parasitized individuals was significantly higher in rock-roosting E. fuscus
      compared with building-roosting E. fuscus, rock- and building-roosting M.
      lucifugus, and rock-roosting M. ciliolabrum and M. evotis. A significant sex bias
      was noted in rock-roosting E. fuscus in 2000 with significantly more females
      parasitized. The number of ticks per bat host was highest in 2001, corresponding
      to the driest and hottest summer of the survey.

PMID- 15962806
TI  - A new Francisella (Beggiatiales: Francisellaceae) inquiline within Dermacentor
      variabilis say (Acari: Ixodidae).
AB  - While estimating the prevalence of the Dermacentor variabilis (Say) symbiont
      (DVS) in dog ticks on Martha's Vineyard, MA, we identified DNA that may represent
      a heretofore unrecognized Francisella sp. Polymerase chain reaction targeting a
      portion of the 16S rDNA specific for DVS yielded an amplicon that was only 96.6%
      similar to that of DVS accessioned in GenBank. Phylogenetic analysis of the 16S
      and 23S rDNA genes suggests the presence of a distinct bacterium closely related
      to the other endosymbionts of Dermacentor spp. Fifty-five percent of dog ticks
      tested from three sites in Massachusetts showed evidence of infection with this
      new agent, called Dermacentor variabilis francisella (DVF), whereas 100% tested
      positive for DVS. All larval progeny of dog ticks known to contain DVF also
      showed evidence of colonization, demonstrating that this agent may be maintained
      by transovarial transmission. Coinfection of ticks with both Francisella species
      did not seem to interfere with transmission.

PMID- 15962807
TI  - Differential infectivity of the Lyme disease spirochete Borrelia burgdorferi
      derived from Ixodes scapularis salivary glands and midgut.
AB  - Blood fed nymphal Ixodes scapularis Say infected with Borrelia burgdorferi were
      dissected to obtain salivary gland and midgut extracts. Extracts were inoculated
      into C3H/HeJ mice, and ear, heart, and bladder were cultured to determine
      comparative infectivity. Aliquots of extracts were then analyzed by quantitative
      polymerase chain reaction to determine the number of spirochetes inoculated into
      mice. A comparative median infectious dose (ID50) was determined for both
      salivary gland and midgut extract inoculations. Our data demonstrated a
      statistically significant difference (P < 0.002) in the ID50 derived from
      salivary gland (average = 18) versus midgut (average = 251) extracts needed to
      infect susceptible mice. A rationale for the differential infectivity of salivary
      and midgut derived spirochetes is discussed.

PMID- 15962808
TI  - Cytokines in Salmonella infections.
AB  - Cytokines are intercellular signal molecules involved in the immune pathogenesis
      of infectious diseases. Cytokine mediated pathological alterations are mainly
      attributable to an imbalance in cytokine production. Experimental and clinical
      studies have documented the fact that Salmonella infections induce a Th1
      dependent immune response and interferon-gamma and interleukin-12 are central to
      its genesis. Salmonella endotoxins, flagellins and porins are among the chief
      mediators of cytokine release. Lectin binding proteins, Toll-like receptors,
      transcription factors and various cells also contribute to this process. Serum
      and local (fecal) cytokine determination in salmonellosis provides evidence on
      the immune events occurring after antigen challenge. They might also serve as
      clinical and prognostic markers of disease severity and outcome. Recent studies
      are focused on the effect and interaction between pro-inflammatory (interleukin
      1, interferon-gamma and tumor necrosis factor) and anti-inflammatory cytokines
      (interleukin-10).

PMID- 15962809
TI  - Female sex hormones and multiple sclerosis.
AB  - Multiple sclerosis is the most frequent debilitating neurological disease in
      young subjects. The autoimmune process predominantly affects females. This paper
      presents a review of experimental and clinical data about the effect of female
      sex hormones and conditions associated with hormonal alterations on the disease
      process. Specific consideration is given to the use of estrogens as a remedy
      influencing the disease course. There haven't been enough studies to indicate
      presence of either hormonal disbalance in females with multiple sclerosis or
      peculiarities in the hormone-cytokine profile during disease relapse and
      remission. Further investigations in this area are needed to provide more
      profound knowledge of the pathogenesis of this socially significant disease.

PMID- 15962810
TI  - Assessment of total antioxidant capacity in human plasma.
AB  - INTRODUCTION: Human serum contains many different antioxidants that may be
      important in the maintenance of antioxidant screen. Aging decreases the level of
      enzymatic and non-enzymatic antioxidant in plasma. In this study we investigated
      total antioxidant capacity in plasma obtained from healthy young and old
      volunteers. MATERIAL AND METHODS: The ferric reducing antioxidant capacity was
      used to measure the total antioxidant capacity of plasma. In in vitro
      experiments, the effects of exogenous compounds (ascorbic acid, uric acid,
      Trolox) on total ferric reducing activity of plasma obtained from young females
      were tested. Total antioxidant capacity of plasma was expressed as micromol
      Trolox equivalent/1 (a water-soluble analog of vitamin E). RESULTS: We
      demonstrated that total antioxidant capacity of plasma obtained from healthy
      young females and males did not differ significantly between each other (22.9 +/-
      1.1 and 24.4 +/- 1.1 micromol Trolox equivalent/1, respectively) and was
      significantly higher than plasma antioxidant capacity of elderly volunteers (15.8
      +/- 1.0 and 16.4 +/- 0.98 micromol Trolox equivalent/1, respectively). In vitro
      addition of ascorbic acid, uric acid, or Trolox to plasma samples significantly
      increased their total antioxidant capacity, but it did not act additively.
      CONCLUSIONS: Our results confirmed that plasma antioxidant capacity declines with
      the volunteers' age and supplementation of antioxidants could be useful for
      enhancement of antioxidant screen in plasma.

PMID- 15962811
TI  - Suicidal behaviour and aggression in psychiatric inpatients.
AB  - OBJECTIVE: Theoretically, suicidal behaviour and aggression are usually said to
      be correlated. Such relationship is, however, not reliably supported by clinical
      and experimental evidence. It has been more frequently found when suicidal
      psychiatric patients are compared with healthy non-suicidal controls rather than
      when the comparison is done within the group of the psychiatric patients.
      Therefore we decided to investigate whether such relationship exists in a group
      with a high risk of suicidal behaviour--psychiatric male inpatients. MATERIAL AND
      METHODS: 113 male inpatients, mostly with schizophrenia and other psychotic
      disorders and mood disorders were studied in the first five days after their
      admission. Using a structured clinical interview and formal rating scales data
      were collected about the number of suicide attempts and aggressive acts committed
      throughout their lives, current suicide ideation and suicide planning behaviour,
      alcohol use, depression and outwardly directed aggression. Correlation analysis
      and chi-square test were used to analyze the data. RESULTS: There is no
      significant relation between current aggressivity and current suicide risk, as
      well as between the lifetime aggression and the lifetime suicide behaviour. The
      current suicide ideation and suicide planning behaviour are related to previous
      suicidal behaviour and to the current depression level. The lifetime aggression
      is related to the alcohol use. CONCLUSIONS: The results of our study do not
      define aggression as a suicide risk factor within the group of psychiatric
      inpatients. This findings could benefit the evaluation of the suicidal risk in
      psychiatric clinic.

PMID- 15962812
TI  - A 25-year experience with standard orchidopexy in cryptorchism.
AB  - We reviewed retrospectively 1466 children aged 1 to 16 years who were operated at
      the Clinic because of cryptorchism between 1979 and 2003. The Gross technique was
      used in 922 (55%) orchidopexies, the Petrivalsky/Schoemaker technique--in 603
      (36%), subcutaneous fixation was performed in 109 cases (6.5%) and surgical
      exploration with or without excision in 42 cases (2.5%). The early results were
      successful in 42% of all cases with intra-abdominal testes, in 74% of cases with
      testes high in the inguinal canal, in 87% of cases with testes located low in the
      canal, and 98% with ectopic testes. Based on these results we consider surgery as
      the principal therapeutic modality to treat cryptorchism which should be
      performed no later than two years of age. We advise using surgical approaches
      other than the standard orchidopexy with inguinal canal exploration in cases of
      high abdominal testes. The results of the present study are discussed alongside
      the data available in the literature.

PMID- 15962813
TI  - Single centre experience of the upper limb replantation and revascularisation.
AB  - Replantation is defined as reattachment of the amputated limb using the
      neurovascular and musculoskeletal structures in order to obtain the recovery of
      the limb. Fortunately, injuries causing limb amputation are rare. Adequate
      treatment within the optimal time scale can provide successful rehabilitation of
      the shape and function of the replanted part. We report the experience of our
      Clinical Centre (regional replantation centre) in the replantation of five
      forearms/hands and revascularisation of six hands between 1997 and 2001. The most
      frequent site of injury was the distal part of the forearm, while the major cause
      of injuries was a wood processing machine. The surgical procedures were performed
      under general anaesthesia within 2-6 hours after injury. Vascular anastomoses,
      nerve repair and muscle repair were performed following the external bone
      fixation. All patients were given anticoagulation treatment postoperatively.
      Thrombosis in the anastomotic site developed as an early complication in two
      patients who underwent thrombectomy; one of these patients developed gangrene and
      underwent amputation. Late postoperative results were good in 10 patients. One
      patient developed acral epidermolysis. Postoperative results after
      revascularisation were good in all patients.

PMID- 15962814
TI  - Electrocardiographic changes after laparoscopic cholecystectomy.
AB  - AIM: To determine whether ECG changes observed after laparoscopic cholecystectomy
      could be correlated with procedure characteristics. MATERIAL AND METHODS. We
      studied prospectively 500 patients who underwent laparoscopic cholecystectomy for
      documented gallstones and prior history of cardiovascular disease, volume of
      carbon dioxide insufflated in the peritoneal cavity, duration of the procedure
      and intra-abdominal pressure created. RESULTS: We found that 9 (1.8%) patients
      developed LV strain, 2 (0.4%) patients--atrial fibrillation, 2 (0.4%) patients-
      tachyarrhythmia in the presence of AF, 1 (0.2%) patient--RBBB and 1 (0.2%)
      patient--myocardial ischemia with ST depression regarding these ECG leads.
      Statistical analysis of the data was performed using multifactorial logistic
      regression analysis. These changes were not correlated to the above referred
      procedure characteristics. CONCLUSION: We conclude that ECG changes are frequent
      events after laparoscopic cholecystectomy (3%) but are not correlated to prior
      history of cardiovascular disease, the duration of the procedure, the volume of
      carbon dioxide insufflated and the intra-abdominal pressure.

PMID- 15962815
TI  - Analysis of stresses in hard dental tissues generated by clinical application of
      retentive root canal posts.
AB  - INTRODUCTION: Exact adjustment of retentive posts to the length of root canals is
      an important prerequisite for the effectiveness of post systems. AIM: To
      determine stresses generated in hard dental tissues of upper and lower canines by
      the application of root canal posts. MATERIAL AND METHODS: The finite element
      method was used to create models of upper and lower canines. Loading by a
      vertical force of Pw = 24 N and a horizontal force of Pv = 15 N was investigated.
      Twenty two partial dentures and total overdentures in 17 patients were
      constructed and retained by devices for intraroot retention, placed in canine
      roots. 16 upper and lower canines were restored by steel posts and composite
      resin cores. RESULTS AND DISCUSSION: Equivalent stresses were the greatest at the
      opening of the root canal. Their maximal values during horizontal loading (6.2 -
      6.8 MPa) were several times as high as the values during vertical loading (1.0 -
      1.1 MPa). The maximal equivalent stresses were in the range of 20 - 25 MPa, when
      the diameter of the root canal was 1.5 x 10(-3) mm smaller than the diameter of
      the post. CONCLUSIONS: Stresses generated in canine roots with retentive posts
      during horizontal loading are greater than the stresses induced by vertical
      loading. Attempts for forceful placement of posts in insufficiently enlarged root
      canals produce stresses of considerable magnitude which could result in cracks
      and fractures of hard dental tissues.

PMID- 15962816
TI  - The smear layer in the root canal and its removal.
AB  - Instrumentation of the root canal during endodontic treatment produces a smear
      layer which is not uniformly attached to the canal wall. Its morphological
      structure comprises dentin particles, organic debris, odontoblast processes,
      microorganisms and their metabolic products. The view that has currently gained
      wide popularity holds that leaving the smear layer in the root canal contradicts
      the principles of efficient treatment as this might compromise the optimal
      progression of the healing process. The proven unfavorable effects of the smear
      layer on treatment outcome bring forward the necessity for additional application
      of agents aimed at its complete removal. As the smear layer has a complex
      structure, these agents should possess a potential for dealing with both its
      organic and inorganic components. The wide range of used medications includes
      different concentrations of sodium hypochlorite as a major irrigant of the root
      canal, chlorhexidine gluconate, chelating agents (EDTA), organic acids, combined
      preparations (MTAD), combined use of agents that can tackle both the organic and
      inorganic components. Lasers find manifold applications in various medical fields
      and can be regarded as a future solution to the problem of total smear layer
      removal. In the present review we have made a critical analysis of currently used
      agents placing the emphasis on the potential use of new medications, capable of
      attacking the smear layer.

PMID- 15962817
TI  - A case of encephalomyelopolyneuropathy in vitamin B12 deficiency.
AB  - A case of a 44-years-old patient with unusual clinical presentation of
      encephalomyelopolyneuropathy in vitamin B12 deficiency is presented. The disease
      manifested itself with gastrointestinal bleeding, which necessitated emergency
      hospitalisation in surgical clinic. Clinical examinations revealed atrophic
      gastritis, pernicious anemia, neurological and mental complications. The
      diagnosis was made according to the following criteria: physical examination-
      smooth tongue, atrophic gastritis, mild hepatosplenomegaly; laboratory findings-
      pernicious anemia, low vitamin B12 serum levels; neurological examination-
      syndrome of combined damage of the posterior and lateral columns of the spinal
      cord; magnetic resonance imaging--typical hyperintense areas on T2-weighted
      images in the posterior columns in the cervical regions of the spinal cord;
      transcranial magnetic stimulation--prolonged central motor conduction time of the
      motor evoked potentials bilaterally; psychological examination--cognitive
      decline. After treatment with vitamin B12 an improvement of the hematological
      findings, neurological deficit and cognitive impairments was found. CONCLUSION:
      Neurological complications could be an early manifestation of vitamin B12
      deficiency. In diagnostic aspect similar complaints require examination of the
      serum levels of vitamin B12. The delay in diagnosis and inadequate therapy bear
      the risk of incomplete recovery of the neurological deficit. The current problem
      of "cognitive decline" necessitates routine examination of the serum levels of
      vitamin Bl2 in all patients with initial cognitive impairments and their prompt
      and approapriate treatment.

PMID- 15962819
TI  - Health plans undaunted by Medicare Part D.

PMID- 15962818
TI  - With more enthusiasm than money, Brailer pushes nationwide EMR system.

PMID- 15962820
TI  - Class action suit: windfall or just wind?

PMID- 15962821
TI  - Compensation monitor. New model, more money for family docs.

PMID- 15962822
TI  - Are consumers really directing their own care?

PMID- 15962823
TI  - Hospitals may see plans as their new confidant.

PMID- 15962824
TI  - Evaporation of retiree benefits may be health plan opportunity.

PMID- 15962825
TI  - Implementing Medicare Part D could get ugly.

PMID- 15962826
TI  - Predictive modeling & genomics: marriage of promise and risk.

PMID- 15962827
TI  - The formulary files. Antiretroviral coverage lacking in 30 percent of ADAPs.

PMID- 15962828
TI  - Microcircuit devices deliver considerable relief from chronic pain.

PMID- 15962829
TI  - Managed care outlook. Covering the uninsured seen as legislative priority.

PMID- 15962830
TI  - It's all about access.

PMID- 15962831
TI  - Strategies for developing a successful Medicare part D formulary.

PMID- 15962832
TI  - Antidementia agents: what is important in this class.

PMID- 15962833
TI  - Tumor necrosis factor inhibitors: following best practice.

PMID- 15962834
TI  - Bisphosphonates: providing strength to a significant class.

PMID- 15962835
TI  - Translating evidence-based information into effective risk communication: current
      challenges and opportunities.
AB  - Recent medical advances and the easy availability of evidence-based information
      at the point of care are believed to provide physicians with improved tools for
      risk communication. However, evidence indicates that physicians still display
      marked variability in ordering tests. Factors that determine a physician's test
      ordering tendencies vary by specialization, practice, geographical location,
      defensive practice, and tolerance of uncertainty and are also modified by patient
      requests. Understanding of statistical terms on the part of both physicians and
      patients remains limited. Physicians may display limited ability to assess
      pretest and posttest probabilities, especially in low- and intermediate-risk
      patients, even after attending short courses in epidemiology, or may find the
      process impractical. Presentation of diagnostic-test results in a natural
      frequency format might improve understanding. Both physicians and patients have
      difficulty grasping the term "number needed to treat" compared with "relative
      risk reduction" when comparing therapeutic options. Other patient-related factors
      that limit understanding include low literacy, individual risk tolerance, and
      framing patterns of the problem (potential gains vs losses). Despite numerous
      available modalities (quantitative and qualitative) of risk communication,
      consensus over the advantage of any single modality in translating evidence into
      risk communication is limited. It is essential that physicians remain patient
      centered, generate trust, and build a partnership with the patient to achieve
      consensus for medical decision-making. Future studies are indicated to assess the
      effectiveness of novel risk-communication modalities based on patients' and
      physicians' characteristics and identify appropriate modality of translating
      evidence (quantitative or qualitative information).

PMID- 15962836
TI  - Alterations of glomerular and extracellular levels of glutathione peroxidase in
      patients and experimental rats with diabetic nephropathy.
AB  - To investigate the status and role of glutathione peroxidase (GPX) in diabetic
      nephropathy, we measured GPX in the plasma and urine of 14 patients with diabetic
      glomerulosclerosis (DGS) and measured glomerular GPX immunostaining in these
      patients and in rats with streptozotocin-induced diabetes of varying duration.
      Plasma GPX levels were significantly lower in DGS patients than in diabetic
      patients without nephropathy (P < .05) or normal controls (P < .01). Urinary GPX
      concentrations were also significantly lower in DGS patients than in diabetic
      patients without nephropathy or normal controls (both P < .05). Immunostaining of
      glomerular GPX was significantly less in DGS patients than in normal controls (P
      < .05) and was negatively correlated with the glomerular sclerosis score and the
      index of mesangial expansion. Serial examination of glomerular GPX in diabetic
      rats showed that immunostaining scores for glomerular GPX in rats were
      significantly lower than those in normal control rats after 1 and 3 months'
      duration of diabetes, and staining scores were also significantly lower in rats
      killed after 3 months of diabetes than in those killed after 1 week. In
      conclusion, our study demonstrates that GPX concentrations in plasma, urine, and
      glomeruli are decreased in individuals with DGS and that the immunostaining of
      glomerular GPX decreases progressively.

PMID- 15962837
TI  - Senile seminal vesicle amyloid is derived from semenogelin I.
AB  - Senile seminal vesicle amyloid (SSVA), one of the most common forms of localized
      amyloidosis, is associated with the male aging process. Although it had been
      posited that the amyloidogenic component originated from exocrine cells and that,
      on the basis of immunohistochemistry, that the amyloid was composed of
      lactoferrin, the nature of SSVA was never established definitively. To address
      this issue, we have used our microanalytic techniques to characterize the
      structure of the congophilic green birefringent protein extracted from 5 such
      amyloid-containing specimens. Mass spectrometric analysis revealed that in all
      cases, the fibrils were composed mainly of polypeptide fragments identical in
      sequence to the N-terminal portion of the major secretory product of seminal
      vesicles, namely semenogelin I (SgI). Although lactoferrin was detected in 3
      instances, the trace amount and seemingly intact form of this molecule indicated
      that it was not the amyloidogenic molecule. The SgI nature of the amyloid was
      confirmed through demonstration that the deposits were immunostained specifically
      with Sgl-reactive antibodies. The results of our research provide unequivocal
      evidence that SSVA is derived from SgI, and we provisionally designate this form
      of amyloidosis as ASgI.

PMID- 15962838
TI  - Antagonism of vascular endothelial growth factor results in microvessel attrition
      and disorganization of wound tissue.
AB  - Vascular endothelial growth factor (VEGF) is a potent growth factor that is
      indispensable for the development of blood vessels in the fetus and for wound
      healing in adults. VEGF likely plays a role in maintaining the blood vessels once
      they have been formed. It is not clear, however, whether a low tissue VEGF
      (caused either by disease or by systemic administration of VEGF antagonists) can
      cause abnormalities in preexisting blood vessels, especially of wound tissue that
      requires high local levels of VEGF for healing. The present study investigated
      the effect of VEGF antagonism on blood vessels of foreign-body granulomas (a
      model of wound-healing tissue). Granulomas were induced by implanting perforated
      polyvinyl tubes into the subcutaneous tissue of rats and allowed to develop for
      14 days, at which time the implanted tubes were completely encapsulated by the
      subcutaneous tissue. The encapsulated granulomas consisted of 3 distinct
      histological layers, of which the middle layer was well perfused by a rich supply
      of microvessels. Morphologically, the granuloma remained "stable" after
      developing for 14 days. At 1 week, VEGF levels in the granuloma fluid, which is
      in equilibrium with the interstitial fluid, were 25 times higher than in the
      plasma. VEGF levels in the granuloma fluid continued to increase for up to 3
      weeks, reflecting the high dependence of the wound tissue on ambient VEGF levels.
      After injection of the VEGF receptor antagonist in the fully formed granuloma,
      the preexisting blood vessels in the middle layer regressed and underwent
      apoptosis, accompanied by expansion of the extracellular matrix (predominately
      collagen I) into areas normally devoid of matrix. We conclude that wound tissue
      is sensitive to ambient VEGF levels, and that a low VEGF condition resulting from
      VEGF receptor antagonism can disrupt the healing of wound tissue.

PMID- 15962839
TI  - Polynitroxyl albumin inhibits inflammation and vasoocclusion in transgenic sickle
      mice.
AB  - Individuals with sickle-cell disease (SCD) and transgenic sickle mice expressing
      human betaS globin exhibit enhanced reactive oxygen species (ROS) production,
      vascular inflammation, and episodic vasoocclusion. We hypothesize that reduction
      of ROS will reduce endothelial-cell activation and adhesion-molecule expression,
      thereby inhibiting vasoocclusion. To test this hypothesis, we measured
      endothelial-cell activation, adhesion-molecule expression, and vasoocclusion in
      sickle mice after administering i.v. polynitroxyl albumin (PNA), a superoxide
      dismutase and catalase mimetic. Untreated sickle mice, compared with normal mice,
      showed increased activation of nuclear factor-kappaB (NF-kappaB), an oxidant
      sensitive transcription factor, in their lungs, livers, and skin. NF-kappaB
      activation was increased further in the livers and skin of sickle but not normal
      mice after hypoxia-reoxygenation. IV administration of PNA inhibited NF-kappaB
      activation by 60% (P < .01) in the lungs and by 33% (P < .05) in the livers of
      sickle mice after hypoxia-reoxygenation. PNA also reduced the expression of
      vascular cell-adhesion molecule-1 (VCAM-1) by 57% in lung (P < .05) and by 33% in
      liver (P < .05) and reduced the expression of intercellular-adhesion molecule-1
      (ICAM-1) by 40% in lung (P < .05) and by 53% in liver (P < .05). PNA inhibited a
      hypoxia-reoxygenation-induced increase in leukocyte rolling (P < .01) and
      adhesion (P < .05) in venules of the dorsal skin. Most importantly, PNA
      completely inhibited hypoxia-reoxygenation-induced vasoocclusion (P < .001).
      Control albumin had no effect on NF-kappaB, VCAM-1, ICAM-1, rolling, adhesion, or
      vasoocclusion. We speculate that therapies to reduce oxidative stress will
      inhibit inflammation and vasoocclusion in SCD.

PMID- 15962840
TI  - Monitoring of cardiac function on the basis of serum troponin I levels in
      patients with acute leukemia treated with anthracyclines.
AB  - Anthracyclines are used extensively in the therapy of hematologic malignancies.
      However, their use has been limited by acute and chronic cardiotoxicity. Cardiac
      troponins have emerged as sensitive and specific markers of even minor myocardial
      damage. In this study we prospectively evaluated serial measurements of serum
      cardiac markers and echocardiography in patients with de novo acute myeloid and
      lymphoid leukemias (AML and ALL, respectively) treated with anthracyclines. We
      examined and subdivided 79 patients into 3 groups: group 1 (37 patients with AML,
      all < 60 years), group 2 (25 with AML, all 260 years), group 3 (17 with ALL).
      Serum specimens were collected before treatment and during and after therapy and
      were analyzed for troponin I (Tnl), myoglobin, creatine phosphokinase-muscle
      myocardium isoenzyme B, and lactate dehydrogenase concentrations. In group 1, 4
      of the 37 patients (11%) had increased levels of Tnl on the 14th day of induction
      therapy, but by the 28th day the Tnl level had returned to normal in 3 of these 4
      patients. In group 2, 3 of the 25 patients (12%) demonstrated increased Tnl
      concentrations on the 7th day of induction therapy, but by the 14th day these
      levels had normalized in 2 of the 3. In group 3, we detected no increased Tnl
      concentrations. Echographic study did show a significant correlation with the Tnl
      levels (P < .001), involving a reversible decrease in left ventricular ejection
      fraction among patients with increased Tnl levels (> 0.15 ng/mL) on day 14 in
      group 1 and on day 7 in group 2. These results may aid the clinician in the
      treatment of patients by identifying high-risk patients who may benefit from
      closer observation or supportive cardiac therapy.

PMID- 15962841
TI  - To publish or not to publish.

PMID- 15962842
TI  - Diabetic injury to the kidney.

PMID- 15962843
TI  - Thickened liquids: practice patterns of speech-language pathologists.
AB  - This study surveyed the practice patterns of speech-language pathologists in
      their use of thickened liquids for patients with swallowing difficulties. A 25
      item Internet survey about thickened liquids was posted via an e-mail list to
      members of the American Speech-Language-Hearing Association Division 13,
      Swallowing and Swallowing Disorders (Dysphagia). Responses of 145 professionals
      who primarily manage adult dysphagia are reported. Although the majority affirmed
      that thickening thin liquids was an effective intervention strategy, opinions
      about effectiveness were more favorable for nectar-thick versus honey-like and
      spoon-thick consistencies. Respondents also acknowledged that their patients had
      little liking for thickened liquids. Results highlight issues related to products
      and staff training, as well as perceptions concerning the factors that might
      affect patients' acceptance of and compliance with use of the products.

PMID- 15962844
TI  - Children's responses to educators' questions in day care play groups.
AB  - An exploratory study examined adults' questions to small groups of children to
      determine how questions influenced their response rate and complexity of
      response. Thirteen educators of toddlers and 13 educators of preschoolers were
      videotaped during free-play. Both groups of educators used an equivalent
      frequency of open-ended and closed questions, but the preschool educators used
      more topic-continuing questions. Consistent with their developmental level,
      preschoolers responded more frequently than toddlers. Toddlers demonstrated few
      effects of question type. In contrast, preschoolers used more multiword
      utterances following open-ended questions and topic-continuing questions.
      Implications for in-service education for staff of early childhood settings
      include increasing the use of both open-ended and topic-continuing questions.

PMID- 15962845
TI  - Does barium influence tongue behaviors during swallowing?
AB  - The validity of videofluoroscopic swallowing assessments rests on the
      understanding that thin, nectar-, honey-, and spoon-thick radiopaque liquids
      resemble nonopaque liquids, both in their consistency and in the variations in
      swallowing that they elicit. Tongue movements during sequential swallows of
      opaque and nonopaque liquids were studied in 8 healthy participants in 2 age
      groups (<30 years, >50 years) using electromagnetic midsagittal articulography.
      Differences included smaller sip size, longer oropharyngeal transit times, and
      greater variability in tongue movement patterns with opaque liquids compared to
      nonopaque liquids, but effect sizes for these differences were small. Transit
      times were significantly longer for older participants than younger participants.
      We recommend matching radiopaque bolus size in videofluoroscopy to the patient's
      habitually preferred sip mass for comparator nonopaque liquids.

PMID- 15962846
TI  - Story presentation effects on children's retell content.
AB  - This study investigated the possibility that the amount of content children
      include in their stories is affected by how stories are presented. Simple stories
      were presented to kindergarten and Grade 2 children in 3 conditions: orally (oral
      only), pictorially (pictures only), and combined oral and pictures. The
      kindergarteners recalled more content in the combined condition than in pictures,
      only. The 2nd graders recalled more content in the oral only and combined
      conditions than in pictures only. The grades differed in both conditions
      involving oral presentation, but not in the pictures only condition. Thus,
      children in both grades provided more story information when they retold a story
      presented orally than when they told the story from pictures alone.

PMID- 15962847
TI  - Dysphagic independent feeders' justifications for noncompliance with
      recommendations by a speech-language pathologist.
AB  - The purpose of this study was to examine the various ways in which independent
      feeding patients with dysphagia justified their noncompliance with swallowing
      recommendations suggested by a speech-language pathologist (SLP). Sixty-three
      independent-feeding dysphagia patients between the ages of 65 and 100 years who
      had been identified by the SLP or staff as noncompliant with SLP recommendations
      were interviewed about their reasons for noncompliance. Reasons were classified
      into 8 categories: (a) denial of a swallowing problem, (b) dissatisfaction with
      the preparations such as thickened liquids or pureed foods, (c) assuming a
      calculated risk for noncompliant behaviors, (d) rationalizing their noncompliance
      in the face of contradictory evidence, (e) minimization of the severity of their
      problem, (f) verbal accommodation while maintaining noncompliance, (g) projection
      of blame toward the SLP, and (h) deflection of noncompliance by referring to an
      external authority. Reasons for noncompliance were discussed in light of theory
      and research on denial, coping mechanisms, and the social-cognitive transition
      model. Implications were drawn for SLP practice in dealing with noncompliant
      independent-feeding patients with dysphagia.

PMID- 15962848
TI  - Reduplication revisited: functions, constraints, repairs, and clinical
      implications.
AB  - This case study considers the phonological forms of early lexical items produced
      by 1 normally developing boy, from 19 to 22 months of age, who began to produce
      all monosyllabic words as bisyllabic. In order to link this empirical data (the
      apparent creation of increased complexity) with universal tendencies (motivated
      by the reduction of complexity), the functions of reduplication were revisited.
      Phonological processes (i.e., reduplication and final consonant deletion) are
      viewed as repairs motivated by 2 interacting constraints (i.e., constraints on
      monosyllabic words and on word-final consonants). These longitudinal case study
      data provide further evidence for a relationship between final consonant deletion
      and reduplication. A possible treatment approach for similar patterns
      demonstrated clinically is recommended.

PMID- 15962849
TI  - [Perioperative thrombosis prophylaxis--where are we going?].

PMID- 15962850
TI  - [Thromboprophylaxis in hip and knee arthroplasty. Are the new anticoagulants
      better than those previously used?].

PMID- 15962851
TI  - [Antibiotics and overweight].

PMID- 15962852
TI  - [Salla disease].

PMID- 15962853
TI  - [Hand hygiene: hand infections and handwashing].

PMID- 15962854
TI  - [The cost-effectiveness of fondaparinux compared to enoxaparin as prophylaxis for
      deep-vein thrombosis in Denmark].

PMID- 15962855
TI  - [Overweight and psychiatric disease. Preliminary experiences from a psycho
      educative weight reduction program].

PMID- 15962856
TI  - [The term happiness pill is a problematic Danish phenomenon].

PMID- 15962857
TI  - [Communication between cancer patients and physicians regarding unconventional
      treatments].

PMID- 15962858
TI  - [Oral transmucosal fentanyl: suitable as an analgesic for children in emergency
      departments].

PMID- 15962859
TI  - [Salla disease in Danish children. The first two cases of Salla disease in Danish
      children].

PMID- 15962860
TI  - [Deep venous thrombosis and fatal pulmonary embolism in a physically restrained
      patient].

PMID- 15962861
TI  - [Myoclonus following combined spinal-epidural anesthesia].

PMID- 15962862
TI  - [Dietary Recommendations 2005].

PMID- 15962863
TI  - [Eye diseases: new therapeutic possibilities. Implantation technology in hearing
      loss].

PMID- 15962864
TI  - [Picture of the month: orbital sclerosis fibrosis].

PMID- 15962865
TI  - [Does the introduction of electronic medical records affect the use of ambulatory
      services?].

PMID- 15962867
TI  - [Drainage treatment of secretory otitis media 2].

PMID- 15962866
TI  - [Clinical intervention research: two editorials and one discussion].

PMID- 15962868
TI  - [Obesity surgery reduces the mortality: medical journalism].

PMID- 15962869
TI  - Asthma: versatile treatment for a variable disease.
AB  - OBJECTIVE: This review describes factors contributing to the variable nature of
      asthma and the versatile treatment strategies required for the clinical
      management of the disease. DATA SOURCES: A comprehensive review of the literature
      using MEDLINE was conducted. STUDY SELECTION: Included articles were selected for
      their relevance to variability or severity of asthma. Bibliographies of selected
      articles served as additional sources of considered publications. RESULTS: Asthma
      severity can vary substantially among patients and within individual patients
      because of physiologic, environmental, or behavioral factors. Inhaled
      corticosteroids are an effective and versatile treatment option for special
      populations with asthma and for patients with varying degrees of asthma severity.
      Inhaled corticosteroids are now the preferred treatment for all three severity
      levels of persistent asthma, especially in young children and pregnant women.
      Treatment regimens may be adjusted up or adjusted down when appropriate to
      maintain optimal symptom control and limit potential adverse systemic effects.
      CONCLUSIONS: The clinical management of asthma is challenging given the day-to
      day variability of the disease. Variability in pulmonary function and asthma
      symptoms may be minimized through increased awareness of the factors contributing
      to asthma variability as well as the effective use of inhaled corticosteroid
      therapy. Flexible treatment strategies that consider the different severities of
      asthma and account for variability within individual patients may be particularly
      useful in improving adherence and patient outcomes.

PMID- 15962870
TI  - Ventilator strategy for status asthmaticus in pregnancy: a case-based review.
AB  - Asthma is a common and potentially serious condition complicating pregnancy.
      However, the literature available on the management of severe asthma in pregnancy
      is limited. We describe two episodes of respiratory failure due to asthma in
      pregnant women and discuss their management in the context of a review of the
      literature. In both patients, adequate oxygenation was maintained by using
      controlled hypoventilation with a permissive hypercapnia strategy. Both patients
      received aggressive steroid therapy, aerosolized bronchodilators, sedation, and
      paralysis. Aggressive asthma treatment as in a nongravid female is recommended.

PMID- 15962871
TI  - Management of asthma among community-based primary care physicians.
AB  - BACKGROUND: Despite significant improvements in asthma treatment and the
      dissemination of national and international guidelines for asthma management,
      there are ongoing concerns that suboptimal care is being provided for patients
      with asthma. OBJECTIVE: To determine the current practice patterns of asthma care
      among primary care physicians. DESIGN: A cross-sectional study. SETTING: Province
      of Alberta, Canada (population: 3 million people). PARTICIPANTS: Patients, 5
      years of age or older, who had a physician's diagnosis of asthma, and had at
      least two visits for asthma between 1996 and 2001. MEASUREMENT AND RESULTS:
      Charts of 3072 distinct patients (from 45 unique primary care physicians) were
      reviewed. Previous emergency department visits or hospitalizations were
      experienced by 20% of the sample. A total of 25% of patients had documented
      evidence that they had performed spirometry. More than half of the patients had
      no documented evidence that they had received any form of asthma education; only
      2% of the charts indicated that patients received a written action plan. Two
      thirds of the patients were prescribed an inhaled steroid within 6 months of the
      last clinic visit. CONCLUSIONS: Our study indicates a gap in the provision of
      asthma education, written action plans, and spirometric testing for patients
      diagnosed with asthma among primary care physicians.

PMID- 15962872
TI  - Bacterial contamination of spacer devices used by asthmatic children.
AB  - OBJECTIVES: To investigate bacterial contamination in spacer devices used by
      asthmatic children and the device maintenance procedures practiced by parents.
      METHODS: Spacer devices used by 62 asthmatic children were examined. Swabs taken
      from the inner surface of the reservoirs and face masks were cultured. Parents
      were interviewed regarding their spacer cleaning and disinfection routines.
      RESULTS: Bacterial contamination was noted in 22 reservoirs (35.5%) and 16 masks
      (25.8%). Pseudomonas aeruginosa was isolated from 21.0% of the reservoirs and
      14.5% of the face masks, Klebsiella pneumoniae from 6.5% and 4.8%, and
      Staphylococcus aureus from 9.7% and 8.1%, respectively. Only 34 parents (54.8%)
      reported that they received cleaning and maintenance instructions from the
      medical staff at initiation of spacer use by their child, and only 38 (61.8%)
      cleaned the device after each use. CONCLUSION: Bacterial contamination is common
      in spacer devices. This study demonstrates that contamination rates are
      significantly lower when parents clean and actually dry (preferably with an air
      blower) spacer devices after each use. Spacer device maintenance should be
      emphasized in education programs for managing asthma.

PMID- 15962873
TI  - Correct use of three powder inhalers: comparison between Diskus, Turbuhaler, and
      Easyhaler.
AB  - A Phase IV, 4-week, open, randomized multicenter parallel group trial compared
      correct use and acceptability of Diskus, Turbuhaler, and Easyhaler powder
      inhalers among 326 inhaler naive asthmatics/symptomatics. The subjects were asked
      to read the instruction leaflet before taking one dose at the first visit. The
      correct use was evaluated when the subject took the dose. After that, the
      subjects were instructed in correct use. The use of the devices was also
      videotaped at every visit, and independent referees judged correct use.
      Acceptability was evaluated by a questionnaire. At the first visit, the
      proportions of subjects who used the devices correctly were as follows:
      Easyhaler, 45%; Diskus, 43%; and Turbuhaler, 51%. The corresponding figures at
      the last visit were 84%, 89%, and 81%. The differences at any visit were not
      statistically significant. Acceptability was greater for Easyhaler and Diskus for
      three of eight items throughout the study, all pertaining to receiving the powder
      from the device and control of the inhalation of the powder. Patient education in
      the use of devices is important, because only half of the subjects used the
      devices correctly, and still after 4 weeks 10-20% could not use the devices
      satisfactorily, regardless of which device.

PMID- 15962874
TI  - Health care use and quality of life among patients with asthma and panic
      disorder.
AB  - The purpose of this study was to assess the associations between panic disorder
      (PD) and health services use, health-related quality of life, and use of short
      acting beta2-agonists among individuals with asthma. We studied 21 adults with
      comorbid asthma and panic disorder (asthma-PD) and 27 asthma patients without PD
      (asthma-only). Participants attended a single session at a laboratory to complete
      the study. A retrospective chart review was conducted to assess use of health
      care resources for asthma treatment during the past 12 months. Patients completed
      the Asthma Quality of Life Questionnaire and lung function testing. Asthma-only
      and asthma-PD patients displayed no differences on asthma severity, as measured
      by spirometry and asthma medication class. Asthma-PD patients had more visits to
      their primary care physicians for asthma (p < 0.01) and reported a lower quality
      of life related to asthma (p < 0.01) and greater use of short-acting beta2
      agonists (p < 0.05) than asthma-only patients. These findings were independent of
      pulmonary function, asthma medication class, and sociodemographic status. These
      data show that coexistence of PD in asthma is associated with increased use of
      primary care health resources and greater perceived impairment from asthma,
      independent of asthma severity. These findings indicate a need to develop
      interventions to improve quality of life and self-management of asthma among PD
      patients.

PMID- 15962875
TI  - Relationship between body mass index and asthma characteristics in a group of
      Italian children and adolescents.
AB  - The prevalence of asthma and obesity, two often associated conditions, is
      influenced not only by age and gender but also by lifestyle factors. This study
      aimed to determine whether, in a Mediterranean northern Italian region, Liguria,
      an increased prevalence of obesity could be detected in asthmatic children and
      adolescents and to evaluate the possible relationship between body mass index
      (BMI) and the characteristics and/or severity of asthma. BMI was determined in
      554 asthmatic subjects (2.2-16.1 years) and 625 age-matched controls; BMI was
      expressed as a continuous variable in standard deviation score (SDS) units,
      determined as difference between the individual observed value and the reference
      mean for age and sex, divided by the corresponding standard deviation (BMI-SDS).
      Overweight/obesity was set at BMI-SDS of 2 or more. BMI-SDS was significantly
      higher in controls than in asthmatics (p = 0.04); however, the proportion of
      overweight/obesity subjects (BMI-SDS > or = 2) was similar in controls and in
      asthmatic patients (p = 0.08). Evaluation of the asthmatic group revealed that
      BMI-SDS was independent of gender (p = 0.57), atopic sensitization (p = 0.69),
      and comorbidity with other allergic symptoms (p = 0.60). By contrast, BMI-SDS was
      lower in preschool-age children than in school-age children and adolescents (p <
      0.0001), in subjects with a high rate of acute respiratory tract infections (p =
      0.04), and in those not treated with inhaled corticosteroids (IGCs) (p = 0.02).
      Although an increase in the prevalence of overweight/obesity was not detected in
      asthmatic children and adolescents, the results reported here suggest a
      preventive surveillance of calorie intake and a promotion of physical activity in
      children requiring long-term treatment with inhaled glucocorticosteroids.

PMID- 15962876
TI  - Electronic asthma action plan database: asthma action plan development using
      Microsoft Access.
AB  - We created a user-friendly database for use with asthma management consistent
      with the national guidelines for asthma. A database was designed by using
      Microsoft Access for the creation of asthma action plans that can be shared
      between providers caring for patients with asthma. This database and the use of
      "form entry" improved documentation of asthma action plans, which are
      increasingly being used to assess appropriateness of care. We currently have 400
      asthma action plans in the database. These action plans can be queried to
      document compliance with accepted best practices. Asthma action plans can be
      created and stored in an Access database that is both user-friendly and that can
      be networked to provide more consistent asthma care.

PMID- 15962877
TI  - Sensitivity of the skin prick test and specificity of the serum-specific IgE test
      for airway responsiveness to house dust mites in asthma.
AB  - BACKGROUND: The concept that asthma diagnosis based on allergen-specific IgE
      levels in serum is more accurate than diagnosis based on skin test reactivity is
      controversial. OBJECTIVE: To determine the atopy parameter that correlates most
      closely with airway reactivity to house dust mites in asthma. METHODS: Forty
      three asthma cases were examined retrospectively for data on Dermatophagoides
      farinae-specific bronchoprovocation, serum-specific IgE, and skin prick tests.
      RESULTS: The maximal decreases in FEV1 following bronchoprovocation were
      correlated significantly with both the IgE levels and skin test scores. The
      accuracies of the tests were highest at a cutoff value of class 4 or higher for
      the IgE and of 3+ or higher for the skin test. At the cutoff values, the
      accuracies of both tests were similar (70% vs. 70%). The sensitivity of the skin
      test (81%) was higher than that of the IgE test (67%), whereas the specificity of
      the IgE test (71%) was higher than that of the skin test (52%). The sensitivity
      of the skin test was 91% at 2+ or higher, and the specificity of the IgE test was
      95% at class 6 or higher. CONCLUSION: These results suggest that both the
      specific IgE level and the skin test reactivity are useful parameters in the
      prediction of positive airway responses to house dust mites in asthma. However,
      the skin test is more sensitive, whereas the IgE test is more specific.
      Therefore, these tests can be used in a complementary fashion (i.e., the skin
      test for screening and the specific IgE test for confirmation of the relevant
      allergen).

PMID- 15962878
TI  - The use of synthetic bedding in children. Do strategies of change influence
      associations with asthma?
AB  - BACKGROUND: Epidemiological data suggest in contrast to clinical recommendations
      a negative effect of synthetic bedding on asthma and respiratory symptoms.
      OBJECTIVE: To assess the effects of bedding filled with synthetic material on the
      risk of asthma and respiratory symptoms in 6- to 7-year-old children, taking into
      account allergy-related change of bedding material. METHODS: We analyzed data
      from the ISAAC Phase III cross-sectional survey (1999/2000) in Munster, Germany.
      Data were collected by parental report from representative school-based samples
      of 6- to 7-year old children (n = 3,529). We calculated prevalence ratios with
      95% confidence intervals for the association between respiratory symptoms
      suggestive of asthma and synthetic pillows and blankets and adjusting for
      potential confounders. RESULTS: In the preliminary analyses, synthetic pillows
      and synthetic blankets were positively associated with the studied respiratory
      outcomes. For example, a high number of wheezing attacks was positively
      associated with synthetic pillows (PR = 4.44; 95% CI 2.84-6.94) and synthetic
      blankets (PR = 3.80; 95% CI 2.48-5.82). However, in the restricted analysis,
      excluding participants reporting allergy-related change of bedding (pillows n =
      440; blankets n = 437), the positive associations disappeared for all studied
      outcomes. CONCLUSIONS: Our findings suggest that allergy-related choice of
      bedding is an important factor in the assessment of the relation between
      synthetic bedding and asthma symptoms. Ignoring those changes can lead to false
      positive risk estimates. Prospective studies that allow to disentangle the
      temporal sequence of disease, exposure, and change of bedding should help to
      further clarify this issue.

PMID- 15962879
TI  - Differences in asthma clinical outcomes according to initial severity.
AB  - Information on asthma morbidity outcomes in relation to the initial degree of
      severity is scarce. OBJECTIVE: To determine the differences in asthma morbidity,
      quality of life (QOL), and lung function outcomes according to the initial
      severity of the illness. METHOD: A cohort of 235 (102 mild, 69 moderate, and 64
      severe) asthma patients was followed up for 3 years. The following parameters
      were collected for all patients: asthma morbidity, clinical data, spirometry, and
      St. George's Respiratory Questionnaire (SGRQ). RESULTS: A significant reduction
      in asthma morbidity and an improvement in pulmonary function and QOL were
      observed in the total group 3 years later. However, when the sample was
      stratified according to the initial severity, differences were observed between
      means in the third year compared with the first year in the following: number of
      primary care visits (patient/year) due to asthma: mild -1 (95% CI: -1.42 to 
      0.56); moderate -0.9 (-.92 to 0.18); and severe 1 (-0.23 to 2.27) (p = 0.020);
      FEV, (%): mild 8.5 (-5.3 to 11.6), moderate -0.3 (-3.2 to 2.6), and severe -1.5 (
      5 to 2) (p < 0.001); and total score of the SGRQ: mild -9.8 (-12.2 to -7.3),
      moderate -9.1 (-12.9 to -5.2), and severe -7.9 (-11.9 to -3.9) (p < 0.001).
      CONCLUSIONS: We conclude that asthma prognosis varies according to the initial
      severity. Clinical, QOL, and pulmonary function outcomes in the mild asthma group
      are better than in the moderate and severe groups.

PMID- 15962880
TI  - The prevalence of reversible airflow obstruction and/or methacholine
      hyperreactivity in random adult asthma patients identified by administrative
      data.
AB  - BACKGROUND: Asthma is a chronic inflammatory lung disease. It is commonly
      diagnosed and treated on the basis of clinical impression, although national
      guidelines recommend documenting reversible airflow obstruction. OBJECTIVES:
      Determine the frequency of reversible airflow obstruction, and/or methacholine
      hyperreactivity during 2003 in a well-characterized population with a low-risk
      asthma diagnosis during 2001. METHODS: Of a total population of 7460 low-risk
      adult (18-64 years) asthma patients (no hospitalizations or emergency department
      visits; < 3 oral steroid courses; < 12 beta-agonist canisters; and < 3
      prescibers, all in prior 12 months) cared for by a large health care program, a
      random sample of 400 was recruited to undergo a diagnostic asthma evaluation. The
      evaluation included a physical examination, medical record review,
      questionnaires, allergy testing, spirometry for airflow obstruction and
      reversibility, and/or methacholine hyperreactivity. RESULTS: Of the 400 randomly
      selected patients, 106 (26.5%) started and 82 (77.3%) completed the asthma
      evaluation. Evaluated subjects were predominately female (71%), middle-aged (mean
      51.0 +/- 11.0 years), diagnosed asthmatics for long duration (mean 22.1 +/- 17.5
      years), and nonsmokers (88.7%). Asthma was confirmed in 62.1% (51 of 82) based on
      a deltaFEV1 12% or greater after albuterol (n = 38), deltaFEV1 15% or greater
      after Advair (n = 6), or a positive methacholine challenge (n = 7). Only 35 of
      400 patients (8.7%) ever had reversibility measured in their medical record. Of
      these, only 12 (34.3%) had a deltaFEV1 12% or greater after albuterol.
      Reversibility was confirmed in all six who had asthma evaluations. CONCLUSIONS:
      More than one third of low-risk adult asthmatics cannot be confirmed to have
      asthma 2 years later. Spirometry that documented reversibility in the medical
      record accurately predicted asthma confirmation. Physicians should more widely
      perform spirometry with reversibility to establish the diagnosis of asthma as
      recommended by national asthma guidelines.

PMID- 15962881
TI  - [Medical controversies--new articles in Lakartidningen. Socratic debates carry
      the knowledge forward in spite of a fragile scientific basis].

PMID- 15962882
TI  - [Sugar triggers our reward-system. Sweets release opiates which stimulates the
      appetite for sucrose--insulin can depress it].
AB  - The consumption of sweet food has increased in Sweden, as in other Western
      countries. The type of food item has changed. The sweet is dominated by soft
      drinks. Appetite regulation for sucrose has been described in experimental animal
      models. It has been found that opioids stimulate appetite for sucrose. At the
      same time sucrose releases endogenous opioids so that a triggering of sucrose
      consumption occurs. Insulin has been shown to decrease sucrose intake by blocking
      the opioid response. Sucrose addiction has been described in rat model. With a
      concentrated sucrose solution to drink an opioid dependence developed with 1)
      increased consumption of sucrose 2) abstinence symptoms with no sucrose and 3)
      anxiety with an opiate blocker. Sucrose addiction in man has not been described
      in the scientific literature. There is an increased liking of sweets with
      alcoholic persons, which may be significant to support a strongly rewarding
      effect of sucrose, also in man. We should limit the access to sweet foods, in
      particular the sweet drinks. Insulin and insulin sensitivity may be an important
      factor to restrict the intake of sweet food.

PMID- 15962883
TI  - [Extremely weak evidence for sugar dependence in humans].

PMID- 15962884
TI  - [Differentiate between eating disorders and dependence--even though the
      biological mechanisms are identical!].

PMID- 15962885
TI  - [New knowledge--also confusing].

PMID- 15962886
TI  - [Genital mutilation of children is an offence. Do health services have a
      sufficient knowledge to see the problem?].
AB  - There are contradicting opinions whether female genital cutting (FGC) takes place
      in Sweden. The results from several studies indicate, however, that FGC is
      practiced on girls residing in Sweden. Almost no research has been done on girls
      on how they are affected by FGC. Thus there is no scientifically based knowledge
      on signs and symptoms in girls related to the practice, which can lead to cases
      passing unnoticed. Many health professionals feel they have poor knowledge about
      FGC. It is important to teach about FGC at medical and nursing schools and to
      make guidelines based on paediatric aspects of FGC.

PMID- 15962888
TI  - [Basal cell cancer should primarily be treated surgically. There are a lot of
      alternative therapeutic methods but few comparative studies].

PMID- 15962887
TI  - [Treatment of osteoporotic vertebral compression. Explosive interest for
      vertebroplasty and kyphoplasty].
AB  - During the last 15 years, two new treatment strategies have gained worldwide
      attention in the treatment of osteoporotic vertebral fractures. The exponential
      increase in the use of percutaneous vertebro- or kyphoplasty has up to now not
      been supported by scientific sound evidence-based data. There exist no
      prospective randomised controlled trials (RCT) that support the efficacy of the
      treatments, not even adequate controlled studies. Instead we have to rely on
      prospective and retrospective uncontrolled short-term observational studies and
      case-control studies. These studies consistently indicate that the short-term
      results after the procedures in the treatment of osteoporotic vertebral fractures
      are favourable, regarding both pain relief and functional status. However, if a
      vertebro- or a kyphoplasty produces a better outcome than conservative treatment,
      and if the long-term results are as favourable as the short-term results in the
      treatment of osteoporotic vertebral fractures, is currently unknown.

PMID- 15962889
TI  - ["Why doesn't it turn out the way you expected?" Reflections on difficulties with
      health care planning in Uganda].

PMID- 15962890
TI  - [Will a national quality registry for diabetes result in better medical
      quality?].

PMID- 15962891
TI  - [Future physicians disseminate the health policy program].

PMID- 15962892
TI  - [Climacteric disorders: more research on different therapeutic alternatives is
      necessary--acupuncture included].

PMID- 15962893
TI  - [Deaf children should learn both sign language and Swedish].

PMID- 15962894
TI  - [Occupational health services, yes, but there are problems].

PMID- 15962896
TI  - [Climate changes and human health].

PMID- 15962895
TI  - [The soldiers had trichinosis].

PMID- 15962897
TI  - [What is your diagnosis? ascaridiasis].

PMID- 15962898
TI  - [Oral rehydration with a plantain flour-based solution precooked with
      standardized electrolytes].
AB  - BACKGROUND: The success of oral rehydration therapy in cases of severe diarrheas
      have led to a need for locally based therapy preparations. A preparation
      consisting of a precooked plantain flour-based solution and standard rehydration
      electrolytes was examined for its effectiveness in treating dehydration, as well
      as its anti-diarrhoeal properties. METHODS: A sample of 101 children, ranging in
      age from 1 to 48 months, was selected, which had presented diarrhea for less than
      one week from onset, with mild dehydration and no associated complications. Fifty
      four children received the ORS/WHO standard treatment, and 47 received a solution
      with electrolytes similar to ORS/WHO, containing 50 g of precooked plantain flour
      instead of glucose (ORS/plantain). RESULTS: Successful rehydration was achieved
      in 94.4% of the children in the ORS/WHO group and 91.5% in the ORS/plantain group
      (p = 0.70). Required time for rehydration was 5.8 (SD +/- 3.0) hours in the
      ORS/WHO group and 6.2 (SD +/- 3.7) hours in the ORS/plantain group (p = 0.31).
      Stool output during rehydration was 7.5 g/kg body weight/hour (SD +/- 7.6) in the
      ORS/WHO group, and 7.05 g/kg/hour (SD +/- 9.4) in the ORS/plantain group (p =
      0.78). No significant differences were noted in the concentrations of plasma
      sodium. The observation period was 22.3 hours (SD +/- 5.3) for the ORS/WHO group
      and 22.7 hours (SD +/- 4.7) for the ORS/plantain group. Stool output during the
      observation period was 5.7 g/kg/hour (SD +/- 4.7) in the ORS/WHO group and 6.3
      g/kg/hour (SD +/- 7.9) in the ORS/plantain group (p = 0.67). The proportion of
      children requiring intravenous fluids during the first 24 hours was 11.1% in the
      ORS/WHO group and 8.5% in the ORS/plantain group (RR = 1.31; 95% CI 0.39-4.35).
      CONCLUSIONS: The plantain flour-based solution proved effective and safe in
      correcting dehydration; however the antidiarrhoeal properties of ORS/plaintain
      were not demonstrated.

PMID- 15962899
TI  - [Phenotypic and genotypic methods for detecting multidrug resistance in
      Mycobacterium tuberculosis].
AB  - BACKGROUND: Expeditious charactization of drug susceptibility in Mycobacterium
      tuberculosis is difficult and, calls for the design and evaluation of faster,
      cheaper and more effective new techniques. OBJECTIVE: The aim of the current
      study was to compare one genotypic and two phenotypic methods for rapid
      susceptibility detection of M. tuberculosis. MATERIAL AND METHODS: Twenty-one M.
      tuberculosis strains were evaluated by phenotypic methodologies of oxidation and
      reduction of Alamar blue and MTT in the presence of streptomycin, isoniazid,
      rifampin and ethambutol. In all tests, the proportion method was applied as the
      comparison standard. By means of receiver operative characteristic (ROC)
      analysis, the performance, predictive values and threshold values for all drugs
      were determined. In addition, the performance of PCR and reverse line blot
      hybridization in establishing predictive values for sensitivity and resistance
      were compared in contingency tables. RESULTS: The susceptibility patterns
      established by colorimetric techniques were obtained after seven days of
      incubation. The performances of these tests were excellent for all drugs-the
      areas under curves were >0.9, 100% of sensitivity (S) and specificity (E) >80%.
      The genotypic method of RFLP oligotyping detected multidrug resistance with S of
      100% and E of 93%. Conclusion. The results indicated that Alamar blue, MTT and
      RFLP methodologies are rapid and useful tools for characterizing multidrug
      resistance in M. tuberculosis, particularly for those patients with high risk of
      developing multidrug resistant tuberculosis.

PMID- 15962900
TI  - [Hepatitis C virus core protein production and purification in a baculovirus
      expression system for biological assays].
AB  - BACKGROUND: The hepatitis C virus (HCV) commonly causes persistent infection. One
      of the viral mechanisms in preventing viral clearance is the ability of HCV to
      induce functional alterations of the immune system cells, specifically of
      dendritic cells. Viral proteins producing the dendritic cell functional
      alterations have been identified as the HCV core protein, which makes up the
      capsid structural unit. OBJECTIVE: One of the limitations to evaluate core
      protein properties is the difficulty in obtaining and purifying the complete
      protein--consisting of 191 amino acids. The aim of the current study was to
      produce and purify the recombinant core protein in a eukaryotic system, and to
      evaluate its effect in human dendritic cell cultures. RESULTS: The core protein
      p23 isoform was expressed in a baculovirus system and purified using isoelectric
      point separation and electroelution. The purity of the core protein was confirmed
      by silver stain and Western blot. These analyses showed the presence of two bands
      that correspond to p23 and p21 isoforms of core protein as previously reported.
      CONCLUSION: The expressed protein differed from naive core protein is terms of
      molecular weight, isoforms and subcellular localization. The procedures developed
      for core protein are applicable for expression of other membrane-associated
      proteins produced in eukaryotic systems.

PMID- 15962901
TI  - [Dental fluorosis in primary school students of the department of Caldas,
      Colombia].
AB  - BACKGROUND: A prevalence survey of dental fluorosis was conducted among primary
      school students in Caldas, a small province in west central Colombia. MATERIALS
      AND METHODS: The cross-sectional study compared the prevalence of dental
      fluorosis in the four regions of Caldas. In the urban area, a probabilistic
      sample was selected and,in the rural areas, students were sampled in locations
      that were readily accessible. One thousand sixty-one students were examined while
      at school in daylight conditions. The surveillance tool applied was the Dean
      Index. Univariate and bivariate analyses were made with a chi-square test being
      applied for the latter to show independence among variables. RESULTS: Sixty-three
      percent (95% CI: 60-66%) of primary school students were affected by fluorosis to
      some degree of severity. Among them, 56% (95% CI: 52-59) were classified in the
      mild and very mild degrees, whereas 7% (95% CI: 2-16) were classified as moderate
      or severe. A statistically significant association between the region variable
      and dental fluorosis was observed. However, no association was found with gender,
      area, schooling or age variables. Within Caldas, the eastern region showed the
      lowest prevalence (47.9%) in contrast to the other three areas (northern, central
      south and western) where prevalences exceeded 68%. CONCLUSIONS: At least two of
      three primary school students in Caldas suffer from some degree of dental
      fluorosis.

PMID- 15962903
TI  - [Characteristics of new cell cultures derived from embryonic tissues of Aedes
      aegypti (Diptera: Culicidae)].
AB  - INTRODUCTION: Cell cultures from insects are a useful methodology in
      technological and biomedical studies. OBJECTIVE: The present work was aimed at
      obtaining and characterizing cell cultures derived from Aedes aegypti embryonic
      tissues. MATERIALS AND METHODS: Embryonated eggs were used for embryonic tissue
      explants in L-15/Grace and MMNP12 culture media, supplemented with 20% fetal
      bovine serum and a mixture of 1% antimycotic and antibiotics, at a pH ranging
      from 6.8 to 7.0. The incubation temperature was 28 degrees C; a CO2 atmosphere
      was not required. RESULTS: Cell growth was obtained in L-15/Grace medium three
      weeks after embryonic tissues explants. Six months were required for achieving a
      confluent monolayer. Twenty-eight serial cell subcultures were carried out from
      August 2003 to June 2004. Cell morphology was characterized as epithelial in the
      later subcultures. Karyotype morphometry as well as molecular and isozymatic
      profiles were established. The cultures were compared with adult samples from the
      species taken from the same colony and with cell lines derived from other
      insects. DISCUSSION AND CONCLUSIONS: These cells are an important in vitro system
      in applied and basic research.

PMID- 15962902
TI  - [Development of a multiantigenic serological test for tuberculosis diagnosis].
AB  - OBJECTIVE: The present work evaluated a multi-antigen printing immunoassay
      (MAPIA) for the serological diagnosis of tuberculosis. MATERIALS AND METHODS:
      Sera were obtained from 66 patients with tuberculosis, verified clinically and
      bacteriologically and from 47 healthy individuals (control group). Sample sera
      were used for detection of antibodies against 3 enriched mixtures of proteins and
      5 unique recombinant antigens. The antigens were presented in a solid matrix.
      Sensitivity, specificity and predictive values were evaluated and confirmed by a
      logistic regression analysis. A prevalence value was calculated and used for the
      selection of the best antigenic combination. RESULTS: The sensitivity and
      specificity values of individual antigens varied between 5-83% and 9-100%. The
      enriched mixtures values were more accurate than those obtained with the
      recombinant antigens. Combinations of several antigens improved the sensitivity
      values up to the 81% level. In most cases, specificity values of 57% or less were
      obtained. CONCLUSIONS: These results suggested that the multiantigenic test can
      be a useful screening tool, to be used in conjunction with the more definitive
      diagnostic tests.

PMID- 15962904
TI  - [Genetic variability of Trypanosoma cruzi in blood and organs of infected mice
      determined by LSSP-PCR].
AB  - BACKGROUND: Chagas' disease, caused by Trypanosoma cruzi, has a variable clinical
      course, ranging from asymptomatic infection to chronic disease. Trypanosoma cruzi
      has a clonal population structure, although infecting strains are often
      multiclonal. Genetic variability of T. cruzi may be one of the determinant
      factors in differential tissue tropism and consequently of the clinical forms of
      the disease. OBJECTIVE: To examine this possibility, mice were infected with two
      Colombian T. cruzi strains to determine the distribution of genetic variants in
      blood and organs. The sensitivity of three molecular markers was evaluated, and
      the genetic variability of the clones was determined. The latter was attained by
      means of low-stringency single specific primer polymerase chain reaction (LSSP
      PCR) using a kinetoplast DNA (kDNA) marker. The kDNA signatures obtained with the
      LSSP-PCR were analyzed by neighbor-joining. RESULTS AND CONCLUSION: The presence
      of the two lineages of T. cruzi was confirmed, as well as the multiclonal
      character of the two strains. The most sensitive marker was the kDNA. The most
      affected organ was the heart, which showed the greatest number of positive
      results with the three markers. Genetic differences were noted between the clones
      from the blood and organs of infected mice. These results support the value of
      the LSSP-PCR technique for the study of the molecular epidemiology of Chagas'
      disease.

PMID- 15962905
TI  - [Identification of the gene sequence of telomerase catalytic subunit in
      Plasmodium falciparum].
AB  - INTRODUCTION: The enzyme telomerase regulates telomere length by synthesis of
      telomeric repeats to compensate for telomeric loss in each DNA replication cycle.
      Therefore, telomerase is a potential target to block growth of cells with high
      replication rates. In Plasmodium falciparum, telomerase activity has been
      documented, but little information on its structure and role. METHODS: Herein,
      alignment of multiple sequences was undertaken comparing telomerase catalytic
      subunit sequences as found in existing databases. A consensus sequence was
      compared with the sequences in the P. falciparum genome project and as a result,
      a candidate sequence for a portion of the telomerase gene was recovered. Primer
      sets were designed for DNA and RNA amplifications. RESULTS: DNA fragments
      corresponding to telomerase conserved domains were amplified by using reverse
      transcription and PCR of cDNA. With a combination of bioinformatics and
      sequencing methods, the sequence of telomerase catalytic subunit gene (TERT) in
      P. falciparum was discovered, and its presence and transcription demonstrated.

PMID- 15962906
TI  - [Effects of vegetal oil supplementation on the lipid profile of Wistar rats ].
AB  - BACKGROUND: Dietary tocopherols, tocotrienols and saturated, mono and
      polyunsaturated fatty acids have been reported to have an effect on blood lipid
      profiles. In Colombia, vegetable oils (palm, soy, corn, sunflower, and canola)
      are a common dietary constituent and consumed in high quantities. OBJECTIVE: In
      the current study, the effects of vegetable oil consumption was examined by
      measuring blood concentrations of triglycerides (TG), total cholesterol (TC) and
      HDL cholesterol (HDL-C) in male Wistar rats. METHODS: The concentrations of
      tocopherols, tocotrienols, and fatty acids in each oil was quantified by High
      Performance Liquid Chromatography (HPLC). Each rat diet was supplemented with 0.2
      ml/day with one oil type. Over a 4-week period, groups of animals were sacrificed
      weekly and blood samples were obtained to quantify TC, TG and HDL-C for each oil
      class. Statistical analyses included mean, standard deviation, ANOVA and
      Bonferroni comparisons tests. RESULTS: Triglyceride content was not affected
      except in the control and the soy group in the third treatment week, although a
      tendency for decreased TG was noted in the palm oil group and for increased TG in
      the sunflower oil and canola oil groups. No significant differences in total
      cholesterol were observed. In HDL-C, significant differences were present for
      every treatment week (p = 0.005); this represented a decreasing trend in palm oil
      group and an increasing trend in the sunflower and corn oil groups. CONCLUSION:
      The oils effected changes in the blood lipid profile. A small amount of saturated
      fatty acids (tocopherol and tocotrienol) were favourable for the HDL-C increase.
      The presenct of tocorienols tended to decrease the TG and probably helped
      attenuate the unfavorable effects of the saturated fatty acids.

PMID- 15962907
TI  - Anti-glucuronoxylomannan IgG1 specific antibodies production in Cryptococcus
      neoformans resistant mice.
AB  - BACKGROUND: Cryptococcus neoformans is a widely disseminated fungus shown to be
      responsible for infections in individuals with impaired cell mediated immunity,
      such as patients with human immunodeficiency virus (HIV). Cryptococcus neoformans
      has a polysaccharide capsule composed of glucuronoxylomannan (GXM), which acts as
      a major virulence factor and is considered to be a thymus independent type-2
      antigen (TI-2). OBJECTIVE: In the current study, the production kinetics were
      evaluated for IgG subclasses specific for GXM, and assessed with the cross
      reactive antibodies to Streptococcus pneumoniae polysaccharide. In addition,
      spleen B cell subpopulations were quantified in murine models of cryptococcosis
      with different susceptibilities to the infection. MATERIALS AND METHODS:
      Antibodies were detected by ELISA at different time intervals after C. neoformans
      infection in moderately resistant (Balb/c), highly resistant (CBA/j) and
      susceptible (C57BL/6) mouse strains. B cells subpopulations were determined by
      flow cytometry analysis. RESULTS: Early production of IgG1, described as
      protector antibodies, coincided with a decrease of the number of C. neoformans
      colony forming units in the lungs. Polysaccharide cross-reactive antibodies were
      detected in each of the three mouse strains. Antibody titers were highest in the
      susceptible strain (C57BL/6), a strain which also showed the highest proportion
      of splenic CD5+ B lymphocytes. In contrast, CBA/J mice showed the highest levels
      of CD43+ B. CONCLUSIONS: These findings suggest that IgG1 antibodies specific for
      GXM, are implicated in host protection against C. neoformans infection and may be
      regulated by CD43+ cells. They also suggest that cross reactivity antibodies are
      not important in the protection against C. neoformans infection.

PMID- 15962908
TI  - [Factor analysis and validation of a Spanish version of the Brief Psychiatric
      Rating Scale in Colombia].
AB  - INTRODUCTION: A validation study was directed toward an evaluation of the Brief
      Psychiatric Rating Scale (BPRS) in a Spanish-language version in Colombia. The
      BPRS is important because it is one of the most widely used scales in clinical
      and research settings in mental health. METHODS: The BPRS was administered to 149
      psychiatric impatients and the scores evaluated for factorial structure and
      internal consistency. Test-retest and inter-rater reliability were assessed in a
      sub-sample of 30 patients. Concurrent validity was analyzed by comparing scores
      on BPRS with scores on GAF scale. Sensitivity to change was evaluated by
      comparing scores in two clinically different settings. RESULTS: Principal
      component factor analysis indicated a structure with three domains:
      schizophreniform, bipolarity and depression. The instrument showed good internal
      consistency (Cronbach's alpha = 0.79). Coefficients corresponding to inter-rater
      and test-retest reliability were 0.94 and 0.82 respectively. Correlation between
      BPRS and GAF was 0.7 (Spearman). Within-subjects ANOVA showed the scale to be an
      instrument good sensitivity for detecting changes in of clinical characteristics.
      CONCLUSION: We concluded that the Spanish language version evaluated in Colombia
      to be a valid clinical-report instrument with adequate psychometric properties.

PMID- 15962909
TI  - [Presence of circulating cytomegalic cells in HIV negative immunosuppressed
      individuals following cytomegalovirus infection].
AB  - OBJECTIVE: Immunofluorenscence methods to detect pp65 antigenemia were
      implemented for identifying the circulating virus-infected cells in individuals
      known to have cytomegalovirus infection and disease symptoms. MATERIAL AND
      METHODS: Between December-2002 and July-2003, 110 peripheral blood samples were
      obtained from 46 immunosuppressed patients. pp65 antigenemia and the presence of
      circulating cells were determined by indirect immunofluorescence using a
      commercial kit to detect CMV pp65 antigen in peripheral blood leukocytes.
      Antigenemia was positive when one or more cells was observed with multilobulated,
      homogenous fluorescent stain in the nucleus. The presence of infected circulating
      cells (peripheral blood mononuclear cells) was determined when an extended
      pattern of fluorescent stain was observed throughout the cytoplasm in cells of 35
      to 50 microm. RESULTS: Eight antigenemias from 7 patients (15%) were positive. Of
      these, 4 (57%) were also positive for circulating infected cells and consisted of
      3 kidney transplant recipients and 1 liver transplant recipient. The number of
      positive cells in antigenemia was greater in kidney-transplant recipients than in
      the rest of immunosupressed patients (457 vs. 1.96, p < 0.005). No association
      was seen between the presence of infected circulating cells, morbidity, mortality
      or the development of GVHD (p < 0.001). CONCLUSION: No correlation was observed
      between the presence of infected cells, antigenemia and mortality. To
      substantiate the lack of correlation amongst these factors, prospective studies
      with larger sample sizes are necessary. These studies will aid in better defining
      the clinical application in immunosupressed patients.

PMID- 15962910
TI  - [The human immunodeficiency virus type 1 and the developing central nervous
      system].
AB  - Currently, at least 42 million people are infected worldwide with the human
      immunodeficiency virus type 1 (HIV-1). Of these, 3.2 million are children
      infected, in 90% of the cases, through vertical transmission. In Colombia,
      approximately 200,000 persons have been infected since the beginning of the
      pandemic, with an increasing trend in the seroprevalence among pregnant women.
      Although HIV-1 is basically lymphotropic, its capacity to invade the central
      nervous system (CNS) is well known, generating multiple neurological alterations,
      especially prominent in children, with encephalopathy being the most prevalent.
      Classically, two types of neurological disorders are recognized in children,
      consisting of early and late encephalopathies, each with differing clinical and
      immunological characteristics. HIV-1 infection of the CNS is limited to
      macrophages, microglia and astrocytes in a restricted manner. In patients with
      acquired immunodeficiency virus (AIDS), neurons are rarely infected, suggesting
      that cellular and viral soluble factors, are responsible for the neuronal damage.
      The conclusion is that the CNS in earlier stages of development is especially
      susceptible to HIV-1 infection. The epidemiological trends predict that these
      types of clinical manifestations of HIV-1 will increase in frequency, and
      increases the necessity for an understanding of the underlying neuropathogenesis.

PMID- 15962911
TI  - [Incomplete epidemiologic surveillance of the Dengue-2 epidemic in Ibague,
      Colombia, 1995-1997].

PMID- 15962912
TI  - Suicide prevention: a vital national public health issue.
AB  - Suicide continues to be a major public health problem in the United States, with
      30,000 deaths per year. The suicide rate, which hovers around 10-12/100,000, has
      remained virtually unchanged over the past three decades. In 1999 the Surgeon
      General proposed a national plan to serve as a roadmap toward developing a
      comprehensive national suicide prevention strategy. The key features of this plan
      were encapsulated in the acronym AIM, Awareness, Intervention and Methodology, to
      define the relevant components of a national strategy. This refers to increasing
      public awareness of the problem of mental illness and suicide, providing
      increased access to treatment and prevention resources and developing improved
      research methodologies. Despite the overall numbers, suicide is a low base-rate
      event, which makes studying intervention and prevention strategies very
      difficult, as very large subject samples are required for meaningful outcome
      assessments. Suicide prevention and prevention research have received
      substantially fewer public resources than many other medical conditions, and
      apparent public health risks such as bioterrorism. It is for this reason that a
      comprehensive, national public health based suicide prevention program is
      required.

PMID- 15962913
TI  - The importance of public sector health care in an underserved population.
AB  - California's employed Latinos are less likely to have private health insurance
      than most other segments of the US population and face a variety of other
      barriers to obtaining health care. To better understand the availability and
      adequacy of health services for these individuals, researchers analyzed data from
      a telephone survey of 1,000 randomly-selected, employed adults. Among all survey
      respondents, a significant percentage obtained their health care from sources
      fully or partially dependent on government financing. Among the uninsured (30.7
      percent of the sample), a majority of those who had a regular source of care
      received services from publicly-supported providers. Dissatisfaction with care
      was infrequent (less than 5 percent of the total sample) and apparently no
      greater among those receiving care from public sources than among those served by
      private doctors. These findings underscore the importance of the public sector in
      providing health care for the underserved, the high quality of the services
      provided (or partially supported) by the public sector, and the seriousness of
      the consequences for the disadvantaged should public support for their healthcare
      diminish.

PMID- 15962914
TI  - Defining and implementing arsenic policies in Bangladesh: possible roles for
      public and private sector actors.
AB  - A UN report warned up to 50% of Bangladesh's population (57 million) are at risk
      of arsenic poisoning from naturally occurring arsenic in well water. This article
      explores how this problem occurred, assesses what factors impede progress
      eliminating this problem and recommends governmental measures for prevention of
      arsenic poisoning.

PMID- 15962915
TI  - The privatization of human services: myths, social capital and civil society.
AB  - It is fashionable to point to privatization and the involvement of for-profits as
      the parties responsible for many, if not most, of the ills that plague the social
      welfare system today. This article takes a contrary point of view. Three
      arguments are made. First, private sector human service delivery and the use of
      for-profits in the United States predate privatization as a defined public
      policy. Second, the privatization of the human services is a world wide
      phenomenon that transcends politics and ideology. Third, the privatization of
      human services helps to promote civil society and generate social capital.

PMID- 15962916
TI  - The State Children's Health Insurance Program: has it reduced the percentage of
      uninsured children?
AB  - Recent data indicate that the percentage of children in the United States who are
      uninsured is declining. Although many factors have contributed to that decline,
      this study assesses the role of public health insurance, specifically the State
      Children's Health Insurance Program (SCHIP), in reducing the percentage of
      uninsured children without health insurance from 1998-2000 and whether Medicaid
      and SCHIP crowd out exists. While this research confirms a significant decline in
      the percentage of uninsured children since SCHIP began enrolling children in
      1998, other factors, including the poverty rate, the percentage of children on
      Medicaid, geographic region and race had a greater impact in explaining that
      result than SCHIP. Lastly, the data findings are consistent with research
      suggesting crowd out does exist.

PMID- 15962917
TI  - Activism in an age of restraint: the resiliency of administrative structure in
      implementing the State Children's Health Insurance Program.
AB  - This article examines state efforts to build administrative structures and
      outreach networks in the State Children's Health Insurance Program (CHIP) through
      a comparative review of 18 states that have been the subject of ongoing research
      by the Nelson A. Rockefeller Institute of Government. The article explores the
      role that institutional structures play at the state level in shaping the
      implementation and administration of federal policy choices. States have
      generally opted to rely largely on existing Medicaid bureaucracies in order to
      implement the new CHIP programs. As a result, CHIP programs have been tightly
      integrated into existing Medicaid structures. Rarely put forward as exemplars of
      responsiveness and, these bureaucracies have nonetheless played a crucial role in
      building and managing CHIP programs across the United States. As this analysis
      will show, this has even been the case in those few states that have opted to
      officially house CHIP administration outside of the Medicaid bureaucracy.
      Furthermore, existing Medicaid systems have often been active as partners and
      participants in efforts to publicize and promote the CHIP program through
      outreach and education efforts. As part of these initiatives, efforts have been
      made to portray CHIP as a form of health insurance rather than a welfare benefit.
      A slight paradox results where key actors in the health and human services
      bureaucracy play an active role in program management while making efforts to
      dissassociate the program from the traditional welfare system. These efforts have
      been largely successful. And in doing so, not only have children been brought
      into the CHIP program but more families have been connected to the Medicaid
      program. In short, a review of state experiences reveals the resiliency and
      flexibility of existing state administrative systems in responding to and
      addressing substantive policy change.

PMID- 15962918
TI  - Antidepressants during pregnancy: new research on fetal outcomes raises
      questions.

PMID- 15962919
TI  - Identification and characteristics of older homeless African American women.
AB  - More older African American women are homeless, with this issue receiving little
      research attention. An exploratory study examined demographics and health
      characteristics of 100 women. Their mean age was 52.55 years (SD = 3.57) and
      ranged from 50 to 74 years. Most were unmarried, homeless more than three months,
      reported more than two diagnoses, and self-rated their health as fair or good.
      Length of time homeless did not significantly influence self-reported health.
      Medical diagnoses increased with time homeless, and rates of some chronic
      diseases were higher than domiciled African American elders 60 years of age and
      over Nearly half (48.5%) of women who were homeless more than 12 months reported
      emotional/mental illness.

PMID- 15962920
TI  - Depression and the adolescent with type 1 diabetes: the covert comorbidity.
AB  - Diabetes and depression have become increasingly linked. The incidence of
      depression in the adolescent diabetic population is especially concerning. The
      purpose of this article is to raise awareness of the association between diabetes
      and depression particularly in the adolescent population. It also discusses
      treatment techniques for the same population. Several treatment techniques have
      proved successful in this population. Psychiatric nurse practitioners and
      advanced practiced nurses are poised to implement these treatments and
      interventions.

PMID- 15962921
TI  - Female sexual assault: the impact on the male significant other.
AB  - In this existential-phenomenological investigation five men were interviewed
      about their experience of being a male significant other (MSO) of a female sexual
      assault victim. The purpose of the study was to understand the MSO's meaning of
      the rape and the emotional impact it had on him. The thematic structure of a
      man's response to having a female significant other sexually assaulted depicts an
      impact on his emotional life in four significant areas: (1) his immediate painful
      thoughts and feelings, (2) his relationship with the victim, (3) his world view
      on male attitudes, and (4) the long-term effects of the trauma. It is an
      experience that has left him feeling angry, helpless, and guilty, prompted him to
      self-inspection, and thus changed him forever.

PMID- 15962922
TI  - Nursing students' attitude change towards mental illness and psychiatric case
      recognition after a clerkship in psychiatry.
AB  - Attitudes towards mental illness were measured in all 92 students of the seventh
      semester in the School of Nursing of Athens University before (time 1) and after
      (time 2) the completion of 40 and 90 hours of lectures on clinical psychiatry and
      clerkship, respectively. The instrument used to measure attitudinal dimensions
      was the Cohen and Struening's Opinions about Mental Illness (OMI) scale, which
      yieldsfive factors and was proven to be reliable and valid in previous studies.
      Hypothetical case vignettes were used to assess psychiatric case recognition. In
      factors A, B, and D statistically significant differences in attitudes towards
      mental illness between time I and 2 were observed. It seems that the completion
      of training in psychiatry influenced the students' opinions about mental illness;
      they expressed less authoritarianism and discriminatory beliefs as well as
      positive views about social integration of mentally ill persons. The group of
      students who failed to recognize the case vignettes satisfactorily also expressed
      negative views in four out of five OMI scale factors.

PMID- 15962923
TI  - Nurse bait: strategies hospitalized patients use to entice nurses within the
      context of the interpersonal relationship.
AB  - Patients on medical-surgical and psychiatric inpatient units long for more and
      deeper connections with nurses. Patients' dependence on the nursing staff, as
      well as their perceived powerlessness, creates a situation where patients believe
      they have to actively find ways to seek needed nursing care. This paper will
      describe active strategies used by medical-surgical patients to entice nurses
      within the context of the nurse-patient relationship; strategies designed to
      mitigate vulnerability and increase interpersonal connection. Implications for
      nursing practice and for Peplau 's Theory of Interpersonal Relations will be
      presented.

PMID- 15962924
TI  - Divorce transition differences of midlife women.
AB  - Divorce transition experienced by and its influence upon midlife women's health
      is not fully understood. Interviews were conducted with 24 divorced women who
      self-classified into decider status groups: initiator (who first decided to end
      marriage), non-initiator (recipient of end of marriage decision), and mutual
      decider (shared decision to end marriage). Interpretive content analysis
      involving pattern coding was conducted. The divorce transition by initiators
      (n=8) included self-focused growth, optimism, and social support losses and
      opportunities, while the divorce transition by non-initiators (n=8) included
      being left, ruminating, vulnerability, and spiritual comfort. No profile emerged
      for the mutual-decider group (n=8). This study supports that differences in
      divorce transition exist for initiators and non-initiators.

PMID- 15962925
TI  - Metabolic activation of the tobacco carcinogen 4-(methylnitrosamino)-(3-pyridyl)
      1-butanone by cytochrome P450 2A13 in human fetal nasal microsomes.
AB  - Among human P450s studied to date, P450 2A13 is the most efficient catalyst of 4
      (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) alpha-hydroxylation. This
      reaction is a key bioactivation pathway in NNK-induced carcinogenesis. P450 2A13
      mRNA has been detected in human tissues, but it is unknown whether the enzyme is
      functional in vivo. Therefore, we studied NNK alpha-hydroxylation in human fetal
      nasal mucosal microsomes, which have been shown to contain high levels of P450 2A
      protein, presumed to be a mixture of P450 2A6 and 2A13. The microsomes
      efficiently catalyzed NNK alpha-hydroxylation at the methylene and methyl
      carbons, as well as carbonyl reduction. Antibodies against mouse P450 2A5
      inhibited alpha-hydroxylation by these microsomes greater than 90%. K(m) and
      V(max) values for alpha-methylene hydroxylation were 6.5 +/- 1.1 muM and 3.0 +/-
      0.1 pmol/min/mg; for alpha-methyl hydroxylation, they were 6.7 +/- 0.8 microM and
      0.85 +/- 0.03 pmol/min/mg. The K(m) values agree closely with those for NNK
      metabolism by P450 2A13. Using a new technique, we separated P450 2A13 from P450
      2A6 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Quantitative
      immunoblot analysis indicated that the level of P450 2A13 in the pooled fetal
      nasal microsome sample used for kinetic analysis was approximately 1.6 pmol/mg
      protein. In the same sample, P450 2A6 was not detected (detection limit, 67
      fmol/mg protein). These kinetic, immunoinhibition, and immunoblot data confirm
      that P450 2A13 is a functional enzyme and the catalyst of NNK alpha-hydroxylation
      in human fetal nasal mucosa. The results are also the first to demonstrate high
      efficiency NNK alpha-hydroxylation in a human tissue.

PMID- 15962926
TI  - Reactive sulfur species: kinetics and mechanism of the oxidation of cystine by
      hypochlorous acid to give N,N'-dichlorocystine.
AB  - Cystine and HOCl (a neutrophil-derived oxidant) react to form an intermediate
      that has a half-life of ca. 5 min at pH 7.5. The intermediate subsequently
      decomposes to eventually yield a mixture of cystine, higher oxides of Cys, and
      other uncharacterized species. Spectral titrations, transitory (1)H NMR and UV
      vis spectra, and the reaction properties of the intermediate are consistent with
      a formulation of N,N'-dichlorocystine {NDC = [-SCH(2)CH(NHCl)(CO(2)H)](2)}. The
      reaction of equimolar amounts of HOCl with cystine at pH 11.3 does not yield N
      chlorocystine [NCC = (-O2C)(H3N+)CHCH(2)SSCH(2)CH(NHCl)(CO(2)H)] but rather a 1:1
      mixture of NDC and cystine. This result could be explained by two mechanisms:
      rapid disproportionation of NCC to produce NDC and cystine or a faster reaction
      of the second equivalent of HOCl with NCC than the first equivalent of HOCl
      reacts with cystine. The latter mechanism is favored because of our observation
      by NMR spectroscopy that NDC decomposes via a species that we have assigned as
      NCC. Thus, disproportionation of NCC is apparently a relatively slow process. The
      rates of reaction of cystine(0) = [-SCH(2)CH(NH(3)(+))(CO(2)(-))](2) degrees ,
      cystine(1-) = [((-)O(2)C)(H(2)N)CHCH(2)SSCH(2)CH(NH(3)(+))(CO(2)(-))](-), and
      cystine(2-) = [-SCH(2)CH(NH2)(CO2)(-))]2(2-) have been investigated, and it is
      clear that cystine(0) is unreactive, whereas cystine(2-) is about four times more
      reactive than cystine(1-). Accordingly, the following mechanism is proposed
      (constants for 5 degrees C): HOCl = H+ + OCl-, pK1 = 7.47; cystine(0) = cystine(1
      ) + H+, pK2 = 8.15; cystine(1-) = cystine(2-) + H+, pK3 = 9.00; cystine(1-) +
      HOCl --> NCC(1-) + H2O, k4 = 4.3(2) x 10(6) M(-1) s(-1); cystine(2-) + HOCl -->
      NCC(2)(-) + H2O, k5 = 1.6(2) x 10(7) M(-1) s(-1); NCC(1-) --> NCC(2-) + H+, k6 =
      fast; NCC(2-) + HOCl --> NDC(2-) + H2O, k7 = fast. At physiologic pH, the k4
      pathway dominates. The generation of long-lived chloramine derivatives of cystine
      may have physiological consequences, since such compounds are known to react with
      nucleophiles via mechanisms that are also characteristic of HOCl, electrophilic
      transfer C+.

PMID- 15962927
TI  - Proteomic identification of potential susceptibility factors in drug-induced
      liver disease.
AB  - Drug-induced liver disease (DILD) causes significant morbidity and mortality and
      impairs new drug development. Currently, no known criteria can predict whether a
      drug will cause DILD or what risk factors make an individual susceptible.
      Although it has been shown in mouse studies that the disruption of key regulatory
      factors, such as cyclooxygenase-2 (COX-2), interleukin (IL)-6, and IL-10,
      increased susceptibility to DILD caused by acetaminophen (APAP), no single factor
      seems to be absolute. As an approach to better understand the multifactorial
      basis of DILD, we compared the hepatic proteome of mice that are resistant (SJL)
      and susceptible (C57Bl/6) to APAP-induced liver disease (AILD), using solution
      based isotope-coded affinity tag (ICAT) liquid chromatography mass spectrometry.
      Several novel factors were identified that were more highly expressed in the
      livers of SJL mice, including those involved in stress response, cell
      proliferation and tissue regeneration, and protein modification, implicating
      these proteins as potential hepatoprotective factors. There was also a selective
      loss of several mitochondrial proteins from the livers of the susceptible C57Bl/6
      mice, suggesting that the loss of functional mitochondria may indeed play a role
      in AILD. These findings indicate that comparative hepatic proteomic analyses of
      susceptible and resistant mouse strains may provide a global approach for
      identifying potential risk factors and mechanistic pathways responsible for DILD.

PMID- 15962928
TI  - Bioactivation of 2,3-diaminopyridine-containing bradykinin B1 receptor
      antagonists: irreversible binding to liver microsomal proteins and formation of
      glutathione conjugates.
AB  - The 2,3-diaminopyridine (DAP) moiety was found to represent a core structure
      essential for the potency of a new series of human bradykinin B(1) receptor
      antagonists. However, incubation of (14)C-labeled 2,3-DAP derivatives with rat
      and human liver microsomes resulted in substantial irreversible binding of
      radioactive material to macromolecules by a process that was NADPH-dependent.
      Trapping the reactive species with GSH led to significant reduction of the
      irreversible binding of radioactivity, with concomitant formation of abundant GSH
      adducts. One type of thiol adducts (detected in both human and rat liver
      microsomes), resulting from addition of 305 Da to the parent compound, was
      observed with all 2,3-DAP compounds. These adducts also were detected in rat
      hepatocyte incubates, as well as in rat bile, following intravenous
      administration of 2,3-DAPs. Formation of the conjugates appeared to involve
      modification of the DAP ring, based upon mass spectral analysis of a number of
      representative GSH adducts; this was corroborated by detailed LC NMR analysis of
      one compound. Formation of this type of GSH conjugate was markedly reduced when
      the 2-amino methyl group linking the 2,3-DAP and the biphenyl moiety was replaced
      with an ether oxygen atom. It is postulated, therefore, that oxidation of the 2
      amino group serves as a key step leading to the formation of reactive species
      associated with the DAP core. In addition, this step appears to be mediated
      primarily by P450 3A, as evidenced by the marked decrease in both the
      irreversible binding of radioactivity and the formation of the GSH adducts in
      human liver microsomes following treatment with ketoconazole and monoclonal
      antibodies against P450 3A. A mechanism for the bioactivation of 2,3-DAP is
      proposed wherein oxidation (dehydrogenation or N-hydroxylation followed by
      dehydration) of the 2-amino group, catalyzed by P450 3A, results in the formation
      of a highly electrophilic species, pyridine-2,3-diimine.

PMID- 15962929
TI  - Screening of human serum proteins for uranium binding.
AB  - About 20% of uranyl ions in serum are associated with the protein pool. A few of
      them such as transferrin have been characterized, but most still have to be
      identified to obtain a better explanation of the biochemical toxicology and
      kinetics of uranium. We designed an in vitro sensitive procedure involving a
      combination of bidimensional chromatography with time-resolved fluorescence,
      coupled with proteomic analysis, to identify uranium-binding proteins in human
      serum fractions. Ten novel targets were identified and validated using purified
      proteins and inductively coupled plasma mass spectrometry. Of these,
      ceruloplasmin, hemopexin, and two complement proteins displayed the capacity to
      bind uranium with stoichiometry greater than 1 mole of uranium per mole of
      protein. Not all of these targets are metalloproteins, suggesting that uranyl
      ions can use a wide variety of binding sites and coordination strategies. These
      data provide additional insights into a better understanding of uranium chemical
      toxicity.

PMID- 15962930
TI  - Structure-activity models for contact sensitization.
AB  - Allergic contact dermatitis (ACD) is a widespread cause of workers' disabilities.
      Although some substances found in the workplace are rigorously tested, the
      potential of the vast majority of chemicals to cause skin sensitization remains
      unknown. At the same time, exhaustive testing of all chemicals in workplaces is
      costly and raises ethical concerns. New approaches to developing information for
      risk assessment based on computational (quantitative) structure-activity
      relationship [(Q)SAR] methods may be complementary to and reduce the need for
      animal testing. Virtually any number of existing, de novo, and even preconceived
      compounds can be screened in silico at a fraction of the cost of animal testing.
      This work investigates the utility of ACD (Q)SAR modeling from the occupational
      health perspective using two leading software products, DEREK for Windows and
      TOPKAT, and an original method based on logistic regression methodology. It is
      found that the correct classification of (Q)SAR predictions for guinea pig data
      achieves values of 73.3, 82.9, and 87.6% for TOPKAT, DEREK for Windows, and the
      logistic regression model, respectively. The correct classification using LLNA
      data equals 73.0 and 83.2% for DEREK for Windows and the logistic regression
      model, respectively.

PMID- 15962931
TI  - Glutathione-mediated formation of oxygen free radicals by the major metabolite of
      oltipraz.
AB  - The major metabolite of the cancer chemopreventive oltipraz (1), a
      pyrrolopyrazine thione, 4, has been shown to be a phase two enzyme inducer, an
      activity thought to be a key to the cancer chemopreventive action of the parent
      compound. To understand the possible mechanism by which the metabolite acts as an
      inducer, a study of its potential to generate free radicals was undertaken.
      Electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1
      pyrroline-N-oxide (DMPO) were performed with 7-methyl-6,8-bis-methyldisulfanyl
      pyrrolo[1,2-a]pyrazine, 5, a synthetic precursor to the metabolite in aqueous and
      organic solvents. In the presence of GSH, which rapidly liberates the metabolite
      from the precursor, a 1:2:2:1 quartet spectrum with hyperfine coupling constants
      a(N) = a(H) = 14.9 G, characteristic of the hydroxyl radical adduct of DMPO, was
      observed in the presence of oxygen. No signal was seen under anaerobic
      conditions. This signal was quenched by the addition of the superoxide scavenging
      enzyme Cu,Zn-superoxide dismutase. In aqueous dimethyl sulfoxide (80 vol % DMSO),
      the metabolite precursor 5, GSH, and DMPO exhibited an EPR spectrum with the
      hyperfine values of a(N) = 12.7 G, a(H1) = 10.3 G, and a(H2) = 1.3 G,
      corresponding to the superoxide radical adduct of DMPO. The amount of superoxide
      radical adduct formed from the reaction of 5 and GSH increases with GSH
      concentration in phosphate buffer solution. Kinetic studies show that the
      formation of superoxide radical anion is first-order with respect to GSH. The
      formation of superoxide radical anion by the metabolite in the presence of GSH is
      linear at lower concentrations of 5 but becomes nonlinear at high concentrations.
      Overall, these studies suggest a mechanism in which GSH reduces the metabolite 4
      to 4. , presumably a radical anion, that in turn donates an electron to oxygen
      resulting in superoxide radical anion formation. This GSH stimulated redox cycle
      of the metabolite 4 suggests a possible mechanism by which the parent compound
      oltipraz might effect the cancer chemopreventive increase in the transcription of
      phase two enzymes that is mediated by transcription factor Nrf2.

PMID- 15962932
TI  - Identification and quantification of the depurinating DNA adducts formed in mouse
      skin treated with dibenzo[a,l]pyrene (DB[a,l]P) or its metabolites and in rat
      mammary gland treated with DB[a,l]P.
AB  - Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogenic polycyclic aromatic
      hydrocarbon and has been identified in the environment. Comparative
      tumorigenicity studies in mouse skin and rat mammary gland indicate that DB[a,l]P
      is slightly more potent than DB[a,l]P-11,12-dihydrodiol and much more potent than
      (+/-)-syn-DB[a,l]P-11,12-dihydrodiol-13,14-epoxide {(+/-)-syn-DB[a,l]PDE} and (+/
      )-anti-DB[a,l]PDE. We report here the identification and quantification of the
      depurinating adducts formed in mouse skin treated with DB[a,l]P, DB[a,l]P-11,12
      dihydrodiol, (+/-)-syn-DB[a,l]PDE, or (+/-)-anti-DB[a,l]PDE and rat mammary gland
      treated with DB[a,l]P. The biologically formed adducts were compared with
      standard adducts by their retention times on HPLC and their spectra obtained by
      fluorescence line-narrowing spectroscopy at low temperature. In mouse skin
      treated with DB[a,l]P, depurinating adducts comprised 99% of the total adducts.
      Most of the depurinating adducts were formed by one-electron oxidation, with 63%
      at Ade and 12% at Gua. The remainder were formed by the diol epoxide, with 18% at
      Ade and 6% at Gua. When mouse skin was treated with DB[a,l]P-11,12-dihydrodiol,
      depurinating adducts comprised 80% of the total, and the predominant one was with
      Ade (69%). Treatment of skin with (+/-)-syn-DB[a,l]PDE resulted in 32%
      depurinating adducts, primarily at Ade (25%), whereas treatment with (+/-)-anti
      DB[a,l]PDE produced 97% stable adducts. The formation of depurinating adducts
      following treatment of rat mammary gland with DB[a,l]P resulted in approximately
      98% depurinating adducts, with the major adducts formed by one-electron
      oxidation. Only one depurinating diol epoxide adduct was formed. Tumorigenicity,
      mutations, and DNA adduct data suggest that depurinating Ade adducts play a major
      role in the initiation of tumors by DB[a,l]P.

PMID- 15962933
TI  - Identification and quantification of stable DNA adducts formed from
      dibenzo[a,l]pyrene or its metabolites in vitro and in mouse skin and rat mammary
      gland.
AB  - The stable adducts of dibenzo[a,l]pyrene (DB[a,l]P) formed by rat liver
      microsomes in vitro were previously quantified, whereas the depurinating adducts
      were both identified and quantified [Li, et al. (1995) Biochemistry 34, 8043]. In
      this article, we report the identification and quantification of the stable DNA
      adducts obtained from DB[a,l]P and DB[a,l]P-11,12-dihydrodiol activated by rat
      liver microsomes and from reaction of (+/-)-anti-DB[a,l]P-11,12-dihydrodiol-13,14
      epoxide (DB[a,l]PDE) and (+/-)-syn-DB[a,l]PDE with DNA in vitro. In addition, the
      stable DNA adducts were identified and quantified following treatment of mouse
      skin with DB[a,l]P, DB[a,l]P-11,12-dihydrodiol, (+/-)-anti-DB[a,l]PDE, or (+/-)
      syn-DB[a,l]PDE in vivo and treatment of rat mammary gland with DB[a,l]P in vivo.
      The DNA adducts were analyzed by the (32)P-postlabeling method, and the major
      adducts were identified by comparison with standards. The six stable adducts of
      DB[a,l]P formed by rat liver microsomes in vitro were either guanine or adenine
      adducts of anti-DB[a,l]PDE or syn-DB[a,l]PDE. About 43% of the detected stable
      adducts from microsomes were with guanine and 44% were with adenine. The pattern
      of adducts formed from DB[a,l]P-11,12-dihydrodiol with microsomes was very
      similar to that from DB[a,l]P. Reaction of (+/-)-anti-DB[a,l]PDE with DNA in
      vitro formed higher levels of stable adducts (55% from guanine and 39% from
      adenine) than (+/-)-syn-DB[a,l]PDE did (about 44% with guanine and 47% with
      adenine). In mouse skin treated with DB[a,l]P, 1% of the total adducts detected
      were stable adducts, comprised of 51% guanine adducts and 46% from adenine; with
      DB[a,l]P-11,12-dihydrodiol, 54% of the total were stable adducts, with a pattern
      of adducts similar to those formed from DB[a,l]P. Treatment of mouse skin with
      (+/-)-syn-DB[a,l]PDE formed 68% stable adducts, mostly at guanine. With (+/-)
      anti-DB[a,l]PDE, mouse skin contained almost exclusively (97%) stable adducts:
      61% guanine adducts and 33% adenine adducts. In rat mammary gland treated with
      DB[a,l]P, 2% of the total adducts were stable, with 42% guanine adducts and 55%
      adenine adducts. Approximately equal to or greater amounts of stable guanine
      adducts were formed in all systems, except for rat mammary gland. In contrast,
      the majority of depurinating adducts were adenine adducts. The carcinogenic
      potencies of these compounds in mouse skin, published earlier, do not
      qualitatively or quantitatively correlate with stable adducts, but rather with
      depurinating adducts.

PMID- 15962934
TI  - Metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide in rats:
      evidence for bioactivation through alcohol-O-glucuronidation and O-sulfation.
AB  - The agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS), was shown
      to be nephrotoxic in rats. Previous studies have indicated that the metabolism of
      NDPS contributes to its mechanism of toxicity and both phase I and phase II
      pathways may be involved. In the current report, we investigated the detailed
      biotransformation of [(14)C]NDPS in rats using HPLC-ESI-MS. The chemical
      reactivity of the phase II NDPS metabolites was also evaluated. In vivo studies
      were conducted by administering [(14)C]NDPS to male Fischer 344 rats. Urine,
      tissue (liver and kidney), and plasma samples were analyzed. The mechanism of
      formation and chemical reactivity of the glucuronide and sulfate metabolites of
      NDPS were investigated in vitro using liver subcellular preparations. Major in
      vivo metabolites of NDPS were identified as the oxidative [N-(3,5-dichlorophenyl)
      2- and 3-hydroxysuccinamic acid, 2-/3-NDHSA] and hydrolytic products [N-(3,5
      dichlorophenyl)succinamic acid]. N-Acetylcysteine and cysteine (with
      intramolecular aminolysis) conjugates were also detected in rat urine and fecal
      extracts, respectively, suggesting the formation of reactive intermediate(s) in
      the metabolism of NDPS. Small amounts of the alcohol-O-glucuronide and O-sulfate
      of 2-/3-NDHSA were detected in rat urine, plasma, and tissue homogenates. The
      formation of these phase II metabolites was found to be mediated through the
      initial conjugation of N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS)
      followed by hydrolysis. As compared to NDHS, NDHS-O-sulfate is approximately 500
      fold more reactive toward GSH conjugation. In rat liver S9, fortifying phase II
      cofactors (UDPGA or PAPS) in incubation mixtures with NDHS also significantly
      increased the amount of GSH adducts produced. Results of this research
      demonstrate that phase II metabolites of NDPS were produced in rats. The
      formation of the alkyl alcohol-O-glucuronide and O-sulfate conjugates represents
      bioactivation pathways in the metabolism of NDPS that could potentially
      contribute to its mechanism of nephrotoxicity.

PMID- 15962935
TI  - Desferrioxamine inhibits production of cytotoxic heme to protein cross-linked
      myoglobin: a mechanism to protect against oxidative stress without iron
      chelation.
AB  - The heme group of myoglobin can form a covalent bond to the protein when met
      (ferric) myoglobin is reacted with peroxides under acidic conditions. This heme
      to protein cross-linked species is highly pro-oxidant and found in the urine of
      patients with rhabdomyolytic-associated acute renal failure. Desferrioxamine, an
      iron-chelating agent used in the treatment of iron overload, is reported to be
      partially effective at preventing kidney failure following rhabdomyolysis. In
      this article, we show that in addition to its capacity as an iron chelator,
      desferroxamine can inhibit the peroxide-induced formation of heme to protein
      cross-linked myoglobin and decreases the pro-oxidant activity of both native and
      heme to protein cross-linked myoglobin. The mechanism of peroxidation and of heme
      to protein cross-linking involves the formation of ferryl intermediate
      (Fe(4+)=O(2-)), and it is by the reduction of this intermediate to the ferric
      form that desferrioxamine can exert inhibitory effects. The concentrations at
      which desferrioxamine inhibits the formation of heme to protein cross-linked
      myoglobin and prevents the pro-oxidant activity of native and oxidatively
      modified myoglobins are comparable to the concentrations used for in vivo studies
      of iron-related oxidative stress. Thus, the ameliorative effects of treatment of
      posthemolytic events by desferrioxamine cannot be exclusively assigned to its
      ability to chelate free iron.

PMID- 15962936
TI  - Synthesis of a 2'-deoxyguanosine adduct of cis-2-butene-1,4-dial, a reactive
      metabolite of furan.
AB  - Furan is a liver and kidney toxicant and a hepatocarcinogen in rodents. Its
      reactive metabolite, cis-2-butene-1,4-dial, reacts with nucleosides to form
      adducts in vitro. The reaction with 2'-deoxyguanosine generates 3-(2'-deoxy-beta
      D-erythropentafuranosyl)-3,5,6,7-tetrahydro-6-hydroxy-7-(ethane-2"-al)-9H
      imidazo[1,2-alpha]purine-9-one as the major reaction product. A synthetic
      approach to this adduct is presented in this report. The key step in this
      synthesis is the preparation of 2'-deoxy-3',5'-O-bis(tert-butyldimethylsilyl)-1
      (1,2,5,6-tetrahydroxyhexan-3-yl)guanosine. Treatment of this intermediate with
      sodium periodate gave three reaction products: a one-substituted adduct, 2'-deoxy
      3',5'-O-bis(tert-butyldimethylsilyl)-1-(2,5-dihydroxy-tetrahydrofuran-3
      yl)guanosine; a 1,N(2)-cyclic adduct, 3-[2'-deoxy-3',5'-O-bis(tert
      butyldimethylsilyl)-beta-D-erythropentafuranosyl]-6-hydroxy-8-formyl-5,6,7,8
      tetrahydropyrimidino[1,2-alpha]purin-10(3H)-one; and the 1,N(2)-bicyclic adduct,
      3-[2'-deoxy-3',5'-O-bis(tert-butyldimethylsilyl)-beta-D-erythropentafuranosyl]
      3,5,6,7-tetrahydro-6-hydroxy-7-(ethane-2"-al)-9H-imidazo[1,2-alpha]purine-9-one.
      The one-substituted and 1,N(2)-cyclic reaction products were unstable and
      rearranged over time to yield the 1,N(2)-bicyclic 2'-deoxyguanosine adducts. The
      desired reaction product was obtained as a mixture of four diastereomers by
      removing the tert-butyldimethylsilyl groups with hydrogen fluoride. This
      synthetic approach to the cis-2-butene-1,4-dial-derived dGuo adducts confirms our
      previous structural characterization of the in vitro cis-2-butene-1,4-dial-dGuo
      reaction product. These studies demonstrate that the observed 1,N(2) bicyclic
      structure is the thermodynamically stable isomer, supporting our previous
      observations that this adduct is the major product formed in vitro. Finally,
      these studies provide the necessary groundwork for the preparation of
      oligonucleotides with site specifically incorporated cis-2-butene-1,4-dial
      derived adducts.

PMID- 15962937
TI  - Tocopherol metabolism using thermochemolysis: chemical and biological properties
      of gamma-tocopherol, gamma-carboxyethyl-hydroxychroman, and their quinones.
AB  - Identification and quantitative estimation of quinone metabolites of gamma
      tocopherol (gamma-T) and its derivative gamma-carboxyethyl hydroxychroman (gamma
      CEHC) are complicated by their functions as arylating electrophiles. We
      hypothesize that their biological properties are expressed through arylating
      quinone electrophile addition (Michael reaction) with thiol nucleophiles in cells
      and tissues. Glutathione (GSH) reacted with gamma-tocopheryl quinone (gamma-TQ)
      to form the hydroquinone adduct, which was identified by electrospray time-of
      flight MS (ESI-TOF-MS). Tetramethylammonium hydroxide (TMAH) thermochemolysis
      reduced and methylated quinones and cleaved and methylated thioether adducts.
      These relatively nonpolar derivatives were readily separated by GC and identified
      by MS fragmentation patterns. gamma-CEHC was synthesized and oxidized to a
      product identified as the quinone lactone (gamma-CEHC-QL). TMAH methylated both
      gamma-CEHC-QL and its GSH adduct without opening the lactone ring, and these
      products were separated by GC and identified by MS fragmentation patterns. gamma
      CEHC-QL reacted with both the cysteinyl enzyme papain and fetal bovine serum, and
      TMAH thermochemolysis showed that each product mixture contained unreacted
      precursor and thioether adduct. Cytotoxicities of phenolic precursors, gamma-T
      and gamma-CEHC, and their quinones, gamma-TQ and gamma-CEHC-QL, respectively,
      were compared in COS1, NT2, 3T3, and N2a cell lines. Phenolic precursor gamma-T
      had a small effect only with NT2 and 3T3 cells while gamma-CEHC had no effect in
      any cell line. Arylating quinones were highly cytotoxic in all cell lines with
      gamma-TQ showing a significantly greater cytotoxicity than gamma-CEHC-QL. These
      data are consistent with our arylating electrophile hypothesis as an explanation
      for some biological activities of Ts through their quinone metabolites.

PMID- 15962939
TI  - Nitric oxide-mediated nitrosation of 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline potentiated by hemin and myeloperoxidase.
AB  - N-Nitrosamines formed by nitrosation of heterocyclic amines might initiate colon
      cancer in individuals consuming well-done red meat diets and with inflammatory
      conditions in their colon. This study investigates nitric oxide (NO)-mediated
      nitrosation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and the
      influence of dietary (hemin) and inflammatory [NO, myeloperoxidase (MPO), and
      H(2)O(2)] components on nitrosation. Using the NO donor spermine NONOate (1.2
      microM NO/min) at pH 7.4 with 0.005 mM MeIQx, a product due to NO autoxidation
      was at the limit of detection (1% of total radioactivity recovered by HPLC).
      Product formation increased 13- or 16-fold in the presence of 10 microM hemin or
      85 nM MPO, respectively, with an in situ system for generating H(2)O(2) (glucose
      oxidase/glucose). The nitrosation product and its chloro derivative were analyzed
      by electrospray ionization mass spectrometry, and the product was determined to
      be 2-nitrosoamino-3,8-dimethylimidazo[4,5-f]quinoxaline (N-NO-MeIQx). Nitrosation
      by NO autoxidation was only detected at > or =1.2 microM NO/min and was not
      affected by H(2)O(2). Investigations with hemin determined minimum effective
      components necessary for potentiation: 1 microM hemin, 1 microM H(2)O(2)/min, and
      0.012 microM NO/min. The reactive nitrogen oxygen species (RNOS) produced by
      hemin and MPO had a 4- and 3-fold, respectively, greater affinity for MeIQx than
      those produced by NO autoxidation. Test agents were used to characterize
      nitrosation. Results with catalase, SOD, azide, and NADH are consistent with
      multiple RNOS, the lack of peroxynitrite involvement in nitrosation, and
      peroxidatic potentiation by oxidative nitrosylation rather than nitrosation.
      Using phorbol ester stimulated human neutrophils, the formation of N-NO-MeIQx and
      its modification by test agents was consistent with MPO and not peroxynitrite.
      Thus, nitrosation of MeIQx and its potentiation by hemin and MPO provide a
      mechanism by which well-done red meat consumption and inflammation can generate N
      nitroso compounds and initiate colon cancer under inflammatory conditions, such
      as colitis.

PMID- 15962938
TI  - Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) by PAH o-quinones:
      involvement of reactive oxygen species and copper(II)/copper(I) redox cycling.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants
      and procarcinogens that require activation by host metabolism. Metabolic
      activation of PAHs by aldo-keto reductases (AKRs) leads to formation of reactive
      and redox active o-quinones, which may cause oxidatively generated DNA damage.
      Spectrophotometric assays showed that NADPH caused PAH o-quinones to enter futile
      redox cycles, which result in the depletion of excess cofactor. Copper(II)
      amplified NADPH-dependent redox cycling of the o-quinones. Concurrent with NADPH
      oxidation, molecular oxygen was consumed, indicating the production of ROS. To
      determine whether PAH o-quinones can cause 8-oxo-dGuo formation in salmon testis
      DNA, three prerequisite experimental conditions were satisfied. Quantitative
      complete enzymatic hydrolysis of DNA was achieved, adventitious oxidation of dGuo
      was eliminated by the use of chelex and desferal, and basal levels of less than
      2.0 8-oxo-dGuo/10(5) dGuo were obtained. The HPLC-ECD analytical method was
      validated by spiking the DNA with standard 8-oxo-dGuo and demonstrating
      quantitative recovery. HPLC-ECD analysis revealed that in the presence of NADPH
      and Cu(II), submicromolar concentrations of PAH o-quinones generated >60.0 8-oxo
      dGuo adducts/10(5) dGuo. The rank order of 8-oxo-dGuo generated in isolated DNA
      was NP-1,2-dione > BA-3,4-dione > 7,12-DMBA-3,4-dione > BP-7,8-dione. The
      formation of 8-oxo-dGuo by PAH o-quinones was concentration-dependent. It was
      completely or partially inhibited when catalase, tiron, or a Cu(I) specific
      chelator, bathocuproine, was added, indicating the requirement for H(2)O(2),
      O(2)(-), and Cu(I), respectively. Methional, which is a copper-hydroperoxo
      complex [Cu(I)OOH] scavenger, also suppressed 8-oxo-dGuo formation. By contrast,
      mannitol, sodium benzoate, and sodium formate, which act as hydroxyl radical
      scavengers, did not block its formation. Sodium azide, which can act as both a
      hydroxyl radical and a (1)O(2) scavenger, abolished the formation of 8-oxo-dGuo.
      These data showed that the production of 8-oxo-dGuo was dependent on Cu(II)/Cu(I)
      catalyzed redox cycling of PAH o-quinones to produce ROS and that the immediate
      oxidant was not hydroxyl radical or Cu(I)OOH and that it is more likely (1)O(2),
      which can produce a 4,8-endoperoxide-dGuo intermediate.

PMID- 15962940
TI  - Mass spectrometric analysis of relative levels of pyridyloxobutylation adducts
      formed in the reaction of DNA with a chemically activated form of the tobacco
      specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.
AB  - Exposure to the tobacco-related nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK) and N'-nitrosonornicotine is carcinogenic to humans. Metabolic
      activation of NNK leads to the formation of DNA adducts, which play a critical
      role in NNK carcinogenesis. Adducts specific to NNK result from covalent linkage
      of a pyridyloxobutyl (POB-1-yl) group to DNA. Furthermore, some such adducts are
      unstable, releasing the degradation product 4-hydroxy-1-(3-pyridyl)-1-butanone (4
      HPB). Previous qualitative reports from our laboratory have established the
      chemical structures of the major POB-1-yl-DNA adducts. In this study, we have
      quantitated the levels of each of these adducts in vitro, as well as their
      contribution to the biomarker of DNA pyridyloxobutylation, 4-HPB. Standards for
      the POB-DNA adducts O(6)-(POB-1-yl)dGuo, 7-(POB-1-yl)Gua, O(2)-(POB-1-yl)dThd,
      and O(2)-(POB-1-yl)Cyt were synthesized and used to determine standard responses
      by reverse phase HPLC-electrospray ionization-tandem mass spectrometry (ESI
      MS/MS). DNA was incubated with varying amounts of 4-(acetoxymethylnitrosamino)-1
      (3-pyridyl)-1-butanone in the presence of an esterase, conditions favorable to
      the formation of an active pyridyloxobutylating agent. After sequential enzymatic
      and neutral thermal hydrolysis, isolation, and purification, the
      pyridyloxobutylated mixture was analyzed by HPLC-ESI-MS/MS to quantify the
      relative level of each of these four adducts as well as the released 4-HPB. The
      most abundant product was 4-HPB, which accounted for two-thirds of the analyzed
      mixture. The highest adduct levels measured were those of bases that result from
      loss of deoxyribose upon neutral thermal hydrolysis. These adducts, 7-(POB-1
      yl)Gua and O(2)-(POB-1-yl)Cyt, comprised an average of 23 and 6% of the analyzed
      mixture, respectively. O(2)-(POB-1-yl)dThd and the mutagenic adduct O(6)-(POB-1
      yl)dGuo were detected at the lowest levels, 4 and 2%, respectively. The relative
      levels of adducts determined in this study provide further insight regarding the
      chemical reactivity of the activated form of NNK with respect to DNA bases.
      Furthermore, the analytical standards and mass spectrometric methods used lay the
      groundwork for establishing a representative array of pyridyloxobutylation
      adducts as biomarkers of tobacco exposure in further biochemical and in vivo
      studies.

PMID- 15962941
TI  - Synthesis, characterization, and 32p-postlabeling analysis of DNA adducts derived
      from the environmental contaminant 3-nitrobenzanthrone.
AB  - 3-Nitrobenzanthrone (3-NBA) is a potent mutagen and potential human carcinogen
      identified in diesel exhaust and ambient air particulate matter. 3-NBA forms DNA
      adducts in rodent tissues that arise principally through reduction to N-hydroxy-3
      aminobenzanthrone (N-OH-ABA), esterification to its acetate or sulfate ester, and
      reaction of this activated ester with DNA. We detected 3-NBA-derived DNA adducts
      in rodent tissues by (32)P-postlabeling and generated them chemically by acid
      catalyzed reaction of N-OH-ABA with DNA, but their structural identification has
      not yet been reported. We have now prepared 3-NBA-derived adducts by reaction of
      a possible reactive metabolite, N-acetoxy-N-acetyl-3-aminobenzanthrone (N-Aco-N
      Ac-ABA), with purine nucleosides and nucleotides, characterized them, and have
      shown that they are present in DNA treated with this 3-NBA derivative. Three of
      these adducts have been characterized as the C-C adduct N-acetyl-3-amino-2-(2'
      deoxyguanosin-8-yl)benzanthrone, the C-N adduct N-acetyl-N-(2'-deoxyguanosin-8
      yl)-3-aminobenzanthrone, and an unusual 3-acetylaminobenzanthrone adduct of
      deoxyadenosine, which involves a double linkage between adenine and benzanthrone
      (N1 to C1, N(6) to C11b), creating a five-membered imidazo type ring system.
      According to IUPAC fused ring conventions, we propose the following systematic
      name for this adduct: (9'-(2' '-deoxyribofuranosyl))purino[6',1':2,3]imidazo[5,4
      p](1,11b-dihydro-(N-acetyl-3-amino))benzanthrone. The 3'-phosphates of these
      novel adducts could be 5'-postlabeled using [gamma-(32)P]ATP, although the
      efficiency of labeling was found to be low (less than 20%). However, none of
      these adducts could be detected in DNA from 3-NBA-treated rats by (32)P
      postlabeling. Two of these synthetic adducts were treated with alkali to generate
      nonacetylated adducts, and these were also shown by HPLC to differ from those
      adducts found in rat DNA. Therefore, a different approach to the synthesis of
      authentic standards is needed for the structural characterization of 3-NBA
      derived DNA adducts formed in vivo.

PMID- 15962942
TI  - Prediction of genotoxicity of chemical compounds by statistical learning methods.
AB  - Various toxicological profiles, such as genotoxic potential, need to be studied
      in drug discovery processes and submitted to the drug regulatory authorities for
      drug safety evaluation. As part of the effort for developing low cost and
      efficient adverse drug reaction testing tools, several statistical learning
      methods have been used for developing genotoxicity prediction systems with an
      accuracy of up to 73.8% for genotoxic (GT+) and 92.8% for nongenotoxic (GT-)
      agents. These systems have been developed and tested by using less than 400 known
      GT+ and GT- agents, which is significantly less in number and diversity than the
      860 GT+ and GT- agents known at present. There is a need to examine if a similar
      level of accuracy can be achieved for the more diverse set of molecules and to
      evaluate other statistical learning methods not yet applied to genotoxicity
      prediction. This work is intended for testing several statistical learning
      methods by using 860 GT+ and GT- agents, which include support vector machines
      (SVM), probabilistic neural network (PNN), k-nearest neighbor (k-NN), and C4.5
      decision tree (DT). A feature selection method, recursive feature elimination, is
      used for selecting molecular descriptors relevant to genotoxicity study. The
      overall accuracies of SVM, k-NN, and PNN are comparable to and those of DT lower
      than the results from earlier studies, with SVM giving the highest accuracies of
      77.8% for GT+ and 92.7% for GT- agents. Our study suggests that statistical
      learning methods, particularly SVM, k-NN, and PNN, are useful for facilitating
      the prediction of genotoxic potential of a diverse set of molecules.

PMID- 15962943
TI  - [(O--N--N)PtX] complexes as a new class of light-emitting materials for
      electrophosphorescent devices.
AB  - The synthesis and photophysical properties of the robust Pt(II) emitters [(O--N-
      N)PtX] (HO--N--N = 6-(2-hydroxyphenyl)-2,2'-bipyridine and its derivatives; X =
      Cl, Br, I, or -CC-Ph) are reported. Yellow electroluminescent devices based on
      these materials display a low turn-on voltage (1 cd m(-2) at 4 V) and a high
      luminance (37000 cd m(-2)). Complex 2e, [(F(t)Bu2O--N--N)PtCl], has the highest
      thermal stability and gave the best OLED.

PMID- 15962944
TI  - Photophysical and electrochemical properties of heteroleptic tris-cyclometalated
      iridium(III) complexes.
AB  - Mixed (difluoro)phenylpyridine/(difluoro)phenylpyrazole tris-cyclometalated
      iridium complexes were prepared in order to study the effect of fluorination and
      the pyridine/pyrazole ratio on the emission and electrochemical properties.
      Increasing fluorination and replacement of pyridine by pyrazole both leads to a
      widening of the HOMO-LUMO gap and generally leads to a blue shift in emission.

PMID- 15962945
TI  - A three-dimensional coordination polymer featuring effective ferrimagnetic
      hydroxide-bridged manganese(II) chains.
AB  - A three-dimensional coordination polymer, [Mn3(OH)2Na2(3-cnba)6]n (1) (3-Hcnba =
      3-cyanobenzoic acid), has been synthesized by the reaction of MnCl2, NaN3, and 3
      Hcnba in water. Its crystal structure was determined by single-crystal X-ray
      diffraction. Magnetic studies show that the complex behaves as a three
      dimensional metamagnet built from effective ferrimagnetic Mn(II) chains in which
      spin moments are linked by interactions in an AF-F-AF (F = ferromagnetic and AF =
      antiferromagnetic) sequence in the triangular magnetic repeating unit.

PMID- 15962946
TI  - High-frequency and -field EPR investigation of a manganese(III) N-confused
      porphyrin complex, [Mn(NCTPP)(py)2].
AB  - We report the first high-frequency and -field electron paramagnetic resonance
      (HFEPR) study of a Mn(III) N-confused porphyrin (NCP) complex (NCP is also known
      as inverted porphyrin or 2-aza-21-carbaporphyrin). We have found a striking
      variation in the electronic properties of the S = 2 Mn(III) ion coordinated by
      NCP compared to other Mn(III) porphyrinoid complexes. Thus, inversion of a single
      pyrrole ring greatly changes the equatorial ligand field exerted and leads to
      large magnitudes of both the axial and rhombic zero-field splitting
      [respectively, D = -3.084(3) cm(-1), E = -0.608(3) cm(-1)], which are
      unprecedented in other Mn(III) porphyrinoids.

PMID- 15962947
TI  - Magnetism of [Ni(dmit)2] salts with [meso- and (1S, 2S)-diphenyl-1,2
      ethanediammonium]([18]crown-6)2 supramolecular cations.
AB  - Meso- and (1S, 2S)-diphenyl-1,2-ethanediammonium (DPEDA2+) complexed with
      [18]crown-6 were introduced into [Ni(dmit)2]-based magnetic salts as
      countercations. The configurational difference of DPEDA2+ modulated the crystal
      structure and magnetic behavior of the salts. A two-dimensional (2D) Heisenberg
      antiferromagnetic square lattice was observed in (meso-diphenyl-1,2-ethane
      diammonium2+)([18]crown-6)2[Ni(dmit)2](-)2, which was the first example of a 2D
      magnetic lattice in [Ni(dmit)2]- salts.

PMID- 15962948
TI  - Molecular tectonics: self-complementary supramolecular Se...N synthons directing
      assembly of 1D silver chains into 3D porous molecular architectures.
AB  - Reaction of 2,1,3-benzoselenadiazole (bsd) with AgNO3 results in the formation of
      a novel model example of a Se...N synthon directed molecular network of different
      polymorphs at different temperatures. Alpha-[Ag(bsd)2(NO3)] x 0.5bsd formed at
      ambient temperature, has a 3D porous molecular network constructed with monomeric
      [Ag(bsd)2(NO3)] motif, and has 1D channels that are encapsulated with 1D arrays
      of two-fold-disordered dimeric (bsd)2 guests aggregated by the self-complementary
      nonbonded Se...N interactions. This is the first molecular net directed by
      supramolecular Se...N synthons. The second polymorph, beta-[Ag(bsd)2(NO3)] x
      0.5bsd, formed from an analogous reaction at 50 degrees C, contains a similar 3D
      molecular network constructed with tetrameric [Ag4(bsd)8(NO3)4] motif and 1D
      arrays of well-ordered dimeric (bsd)2 guests are encapsulated in the channels.
      Such ordered (bsd)2 dimers provide an excellent simplified dimeric model for MO
      calculations of intermolecular nonbonded Se...N interactions.

PMID- 15962949
TI  - A giant supramolecular light-harvesting antenna-acceptor composite.
AB  - A giant light-harvesting antenna-acceptor composite was constructed by
      heterodimerization of imidazolylmanganese(III)porphyrin to molecular terminals of
      the zinc porphyrin array composed of meso-meso linked
      bis(imidazolylzincporphyrin). Fluorescence quenching titration indicated that the
      terminal imidazolylmanganase(III)porphyrin quenched excited zinc porphyrin
      separated by a large number of intervening porphyrins and that the meso-meso
      linked bis(imidazolylzincporphyrin) array was an efficient light-harvesting
      antenna.

PMID- 15962950
TI  - 1,4-Di(1,2,3-triazol-1-yl)butane as building block for the preparation of the
      iron(II) spin-crossover 2D coordination polymer.
AB  - The novel bidentate ligand 1,4-di(1,2,3-triazol-1-yl)butane (bbtr) reacts with
      Fe(ClO4)2 x 6H2O to form the 2D coordination polymer with (3,6) network topology.
      The {[Fe(bbtr)3](ClO4)2}infinity represents an example of spin-crossover material
      based on 1,2,3-triazole as donor group, and displays an abrupt spin transition
      accompanied by a thermal hysteresis loop (T(1/2)decrease = 101 K and
      T(1/2)increase = 109 K).

PMID- 15962951
TI  - Diastereoisomerically selective enantiomerically pure titanium complexes of Salan
      ligands: synthesis, structure, and preliminary activity studies.
AB  - The degree of diastereoselectivity in the wrapping of four new chiral Salan
      ligands to form chiral-at-metal titanium complexes ranged from mild to perfect as
      a function of the ligands' N substituents; the enantiomerically pure complexes
      catalyzed the addition of diethyl zinc to benzaldehyde in 73-76% enantiomeric
      excess.

PMID- 15962952
TI  - Metal-organotetraphosphonate inorganic-organic hybrids: crystal structure and
      anticorrosion effects of zinc hexamethylenediaminetetrakis(methylenephosphonate)
      on carbon steels.
AB  - The synthesis and structural characterization of the first polymeric M-HDTMP
      organic-inorganic hybrids are described [M = Zn2+, Ca2+; HDTMP =
      hexamethylenediaminetetrakis(methylenephosphonate)]. The 3D crystal structure of
      the Zn2+ analogue [Zn(HDTMP) x H2O] is described. The Zn center is found in a
      distorted octahedral environment of phosphonate oxygens. There is a long Zn...O
      interaction (2.622 A) originating from a protonated -P-OH group. Synergistic
      combinations of Zn2+ and the tetraphosphonate are found to form films that
      protect against the corrosion of carbon steels.

PMID- 15962953
TI  - Structural and kinetic studies on uranyl(V) carbonate complex using 13C NMR
      spectroscopy.
AB  - We have measured 13C NMR spectra of uranyl(V) carbonate complex in D2O solution
      containing 1.003 M Na2(13)CO3 at various temperatures. Two singlet signals
      corresponding to free and coordinated CO3(2-) were observed at 169.13 and 106.70
      ppm, respectively. From the peak area ratio, the structure of the uranyl(V)
      carbonate complex was determined as [U(V)O2(CO3)3]5-. Furthermore, kinetic
      analyses of the exchange reaction of free and coordinated CO3(2-) in
      [U(V)O2(CO3)3]5- were carried out using 13C NMR line-broadening. As a result, the
      first-order rate constant at 298 K and the activation parameters for CO3(2-)
      exchange reaction in [U(V)O2(CO3)3]5- were evaluated as 1.13 x 10(3) s(-1) and
      deltaH(double dagger) = 62.0 +/- 0.7 kJ x mol(-1), deltaS(double dagger) = 22 +/-
      3 J x mol(-1) x K(-1), respectively. We suggest that the exchange follows a
      dissociative mechanism as in the corresponding [U(VI)O2(CO3)3]4- complex.

PMID- 15962954
TI  - On the nature of carbon-hydrogen bond activation at rhodium and related
      reactions.
AB  - Over the past 20 years, substantial progress has been made in the understanding
      of the activation of C-H and other strong bonds by reactive metal complexes in
      low oxidation states. This paper will present an overview of the use of
      pentamethylcyclopentadienyl and trispyrazolylborate rhodium complexes for the
      activation of arene and alkane C-H bonds. Insights into bond strengths, kinetic
      and thermodynamic selectivities, and the nature of the intermediates involved
      will be reviewed. The role of eta-2 arene complexes will be shown to be critical
      to the C-H activation reactions. Some information about the fleeting alkane sigma
      complexes will also be presented. In addition, use of these complexes with
      thiophenes has shown the ability to cleave C-S bonds. Mechanistic information has
      been obtained indicating coordination through sulfur prior to cleavage. Relevant
      examples of nickel-based C-S cleavage will also be given.

PMID- 15962955
TI  - Synthesis, characterization, and physicochemical properties of manganese(III) and
      manganese(V)-oxo corrolazines.
AB  - The structural and physicochemical properties of the manganese-corrolazine (Cz)
      complexes (TBP8Cz)Mn(V)O (1) and (TBP8Cz)Mn(III) (2) (TBP = p-tert-butylphenyl)
      have been determined. Recrystallization of 2 from toluene/MeOH resulted in the
      crystal structure of (TBP8Cz)Mn(III)(CH3OH) (2 x MeOH). The packing diagram of 2
      x MeOH reveals hydrogen bonds between MeOH axial ligands and meso N atoms of
      adjacent molecules. Solution binding studies of 2 with different axial ligands
      (Cl-, Et3PO, and Ph3PO) reveal strong binding, corroborating the preference of
      the Mn(III) ion for a five-coordinate environment. High-frequency and field
      electron paramagnetic resonance (HFEPR) spectroscopy of solid 2 x MeOH shows that
      2 x MeOH is best described as a high-spin (S = 2) Mn(III) complex with zero-field
      splitting parameters typical of corroles. Structural information on 1 was
      obtained through an X-ray absorption near-edge structure (XANES)/extended X-ray
      absorption fine structure (EXAFS) study and compared to XANES/EXAFS data for 2 x
      MeOH. The XANES data for 1 shows an intense pre-edge transition characteristic of
      a high-valent metal-oxo species, and a best fit of the EXAFS data gives a short
      Mn-O bond distance of 1.56 A, confirming the structure of the metal-oxo unit in
      1. Detailed spectroelectrochemical studies of 1 and 2 were performed revealing
      multiple reversible redox processes for both complexes, including a relatively
      low potential for the Mn(V) --> Mn(IV) process in 1 (near 0.0 V vs saturated
      calomel reference electrode). Chemical reduction of 1 results in the formation of
      a Mn(III)Mn(IV)(mu-O) dimer as characterized by electron paramagnetic resonance
      spectroscopy.

PMID- 15962956
TI  - The first coordination polymers and hydrogen bonded networks containing
      octahedral Nb6 clusters and alkaline earth metal complexes.
AB  - Three novel coordination polymers built of octahedral niobium cyanochloride
      clusters [Nb6Cl12(CN)6] and alkaline earth metal complexes have been prepared by
      reaction of aqueous solutions of (Me4N)4Nb6Cl18 and KCN with solutions of
      alkaline earth metal salts and 1,10-phenanthroline (phen) (1:2 molar ratio) in
      H2O/EtOH. The structures of [Ca(phen)2(H2O)3]2[Nb6Cl12(CN)6] x (phen)(EtOH)1.6
      (1), [Ca(phen)2(H2O)2]2[Nb6Cl12(CN)6] x (phen)2 x 4H2O (2), and
      [Ba(phen)2(H2O)]2[Nb6Cl12(CN)6] (3) were determined by single-crystal X-ray
      diffraction. The three compounds were found to crystallize in the monoclinic
      system (space group Pn) with a = 11.5499(6) A, b = 17.5305(8) A, c = 21.784(1) A,
      beta = 100.877(1) degrees for 1; triclinic system (P1) with a = 12.609(4) A, b =
      13.262(4) A, c = 16.645(5) A, alpha = 69.933(6) degrees, beta = 68.607(6)
      degrees, gamma = 63.522(5) degrees for 2; and a = 16.057(1) A, b = 16.063(1) A, c
      = 16.061(1) A, alpha = 86.830(1) degrees, beta = 64.380(1) degrees, gamma =
      67.803(1) degrees for 3. Compounds 1 and 2 are built of cluster anions
      [Nb6Cl12(CN)6]4- trans-coordinated by two Ca2+ complexes via CN ligands to form
      neutral macromolecular units [Ca(phen)2(H2O)3]2[Nb6Cl12(CN)6] in 1 and
      [Ca(phen)2(H2O)2]2[Nb6Cl12(CN)6] in 2. Water of coordination and cyanide ligands
      form hydrogen bonded 3D and 2D frameworks for 1 and 2, respectively. The
      structure of 3 consists of [Nb6Cl12(CN)6]4- cluster anions and [Ba(phen)2(H2O)]2+
      complexes linked through bridging cyanide ligands to form a neutral three
      dimensional framework in which each barium complex is bound to three neighboring
      Nb6 clusters and each Nb6 cluster is linked to six Ba complexes.

PMID- 15962957
TI  - cis-Dioxomolybdenum(VI) and oxo(phosphine oxide)molybdenum(IV) complexes: steric
      and electronic fine-tuning of cis-[MoOS]2+ precursors.
AB  - The complexes cis-Tp(iPr)Mo(VI)O2(OAr) (Tp(iPr) = hydrotris(3-isopropylpyrazol-1
      yl)borate, -OAr = phenolate or naphtholate derivative) are formed upon metathesis
      of Tp(iPr)MoO2Cl and HOAr/NEt3 in dichloromethane. The orange, diamagnetic dioxo
      Mo(VI) complexes exhibit strong nu(MoO2) IR bands at ca. 930 and 905 cm(-1) and
      NMR spectra indicative of C(s) symmetry. They undergo electrochemically
      reversible, one-electron reductions at potentials in the range -0.714 to -0.855 V
      vs SCE (in MeCN) and react with PEt3 to produce Tp(iPr)Mo(IV)O(OAr)(OPEt3). The
      green, diamagnetic oxo-Mo(IV) complexes display a single nu(MoO) IR band at ca.
      950 cm(-1) and exhibit NMR spectra indicative of C1 symmetry. The crystal
      structures of eight dioxo-Mo(VI) complexes have been determined to assess the
      degree of frontal (O3-donor face) steric congestion at the Mo center, to identify
      complexes amenable to conversion into monomeric oxosulfido-Mo(VI) derivatives.
      The complexes display distorted octahedral geometries, with a cis arrangement of
      terminal oxo ligands, with d(Mo=O)av = 1.694 A and angle(MoO2)av = 103.4 degrees.
      Maximal frontal steric congestion is observed in the 2-phenolate derivatives, and
      these are identified as precursors for strictly monomeric(solid and solution
      state) oxosulfido-Mo(VI) counterparts.

PMID- 15962958
TI  - 3D coordination polymers with nitrilotriacetic and 4,4'-bipyridyl mixed ligands:
      structural variation based on dinuclear or tetranuclear subunits assisted by Na-O
      and/or O-H...O interactions.
AB  - The reactions of Cu(II) with the mixed nitrilotriacetic acid (H3NTA) and 4,4'
      bipyridyl (4,4'-bpy) ligands in different metal-to-ligand ratios in the presence
      of NaOH and NaClO4 afforded two complexes, Na3[Cu2(NTA)2(4,4'-bpy)]ClO4 x 5H2O
      (1) and [Cu2(NTA) (4,4'-bpy)2]ClO4 x 4H2O (2). The two complexes have been
      characterized by elemental analysis, IR, XRD, and single-crystal X-ray
      diffraction. 1 contains a basic doubly negatively charged [Cu2(NTA)2(4,4'-bpy)]2-
      dinuclear unit which was further assembled via multiple Na-O and O-H...O
      interactions into a three-dimensional (3D) pillared-layer structure. 2 features a
      two-dimensional (2D) undulated brick-wall architecture containing a basic doubly
      positively charged [Cu4(NTA)2(4,4'-bpy)2]2+ tetranuclear unit. The 2D network
      possesses large cavities hosting guest molecules and was further assembled via O
      H...O hydrogen bonds into a 3D structure with several channels running in
      different directions.

PMID- 15962959
TI  - 1H NMR investigation of high-spin and low-spin iron(III) meso-ethynylporphyrins.
AB  - The 1H NMR spectra of iron(III) 5-ethynyl-10,15,20-tri(p-tolyl)porphyrin
      [(ETrTP)Fe(III)X(n)], iron(III) 5-(phenylethynyl)-10,15,20-tri(p-tolyl)porphyrin
      [(PETrTP)Fe(III)X(n)], iron(III) 5-(phenylbutadiynyl)-10,15,20-tri(p
      tolyl)porphyrin [(PBTrTP)Fe(III)X(n)], iron(III) 5,10,15,20
      tetra(phenylethynyl)porphyrin [(TPEP)Fe(III)X(n)], iron(III) 1,4-bis-[10,15,20
      tri(p-tolyl)porphyrin-5-yl]-1,3-butadiyne {[(TrTP)Fe(III)X(n)]2 B}, and 5,10,15
      triphenylporphyrin [(TrPP)Fe(III)X(n)] have been studied to elucidate the impact
      of meso-ethynyl substitution on the electronic structure and spin density
      distribution of high-spin (X = Cl-, n = 1) and low-spin (X = CN-, n = 2)
      derivatives. The meso substituents, i.e., ethynyl, phenylethynyl, and
      phenylbutadiynyl, provided insight into the efficiency of spin density
      delocalization along structural elements that are typically applied to transmit
      electronic effects along multipart polyporphyrinic systems. The positive spin
      density localized at the meso-carbon of high-spin iron(III) ethynylporphyrins is
      effectively delocalized along the ethyne or butadiyne fragment as illustrated by
      the comparison of isotropic shifts of C(meso)-H and -CC-H determined for
      (TrPP)Fe(III)Cl (-82.6 ppm, 293 K) and (ETrTP)Fe(III)Cl (-49.5 ppm, 298 K). The
      replacement of the ethynyl hydrogen by phenyl or phenylethynyl provided evidence
      for the pi spin density distribution around the introduced phenyl ring. An
      analysis of the isotropic shifts for the low-spin bis-cyanide iron(III)
      porphyrins series reveals the analogous mechanism of spin density transfer.
      Treatment of high-spin [(TrTP)Fe(III)Cl]2 B with a base resulted in formation of
      the cyclic [(TrTP)Fe(III)OFe(III)(TrTP)B]2 complex linked by two mu-oxo bridges.
      (TPEP)H2 has been characterized by X-ray crystallography as a porphyrin dication
      where two molecules of trifluoroacetic acid associate with two coordinated
      trifluoroacetate anions. The X-ray structure of bis-tetrahydrofuran 1,4
      bis[10,15,20-tri(p-tolyl)porphyrinatozinc(II)-5-yl]-1,3-butadiyne complex
      {[(TrTP)Zn(II)(THF)]2 B} reveals two parallel, non-coplanar [(TrTP)Zn(THF)]
      subunits linked by the linear butadiyne moiety.

PMID- 15962960
TI  - Rational synthesis and magnetic properties of a family of low-dimensional
      heterometallic Cr-Mn complexes based on the versatile building block [Cr(2,2'
      bipyridine)(CN)4]-.
AB  - Six heterometallic compounds based on the building block [Cr(bpy)(CN)4]- (bpy =
      2,2'-bipyridine) with secondary and/or tertiary coligands as modulators,
      {Mn(H2O)2[Cr(bpy)(CN)4]2}n (1), {Mn(bpy)(H2O)[Cr(bpy)(CN)4]2 x H2O}n (2),
      [Mn(bpy)2][Cr(bpy)(CN)4]2 x 5H2O (3), {[Mn(dca)(bpy)(H2O)][Cr(bpy)(CN)4] x H2O}n
      (4) (dca = N(CN)2(-)), {Mn(N3)(CH3OH)[Cr(bpy)(CN)4] x 2H2O}n (5), and
      {Mn(bpy)(N3)(H2O)[Cr(bpy)(CN)4] x H2O}2 (6), have been prepared and characterized
      structurally and magnetically. X-ray crystallography reveals that the compounds
      1, 2, 4, and 5 consist of one-dimensional (1D) chains with different structures:
      a 4,2-ribbon-like chain, a branched zigzag chain, a 2,2-CC zigzag chain, and a
      3,3-ladder-like chain, respectively. It also reveals that compound 3 has a
      trinuclear [MnCr2] structure, and compound 6 has a tetranuclear [Mn2Cr2] square
      structure. Magnetic studies show antiferromagnetic interaction between Cr(III)
      and Mn(II) ions in all compounds. All of the chain compounds exhibit metamagnetic
      behaviors with different critical temperatures (Tc) and critical fields (Hc; at
      1.8 K): 3.2 K and 3.0 kOe for 1; 2.3 K and 4.0 kOe for 2; 2.1 K and 1.0 kOe for
      4; and 4.7 K and 5.0 kOe for 5, respectively. The noncentrosymmetric compound 2
      is also a weak ferromagnet at low temperature because of spin canting. The
      magnetic analyses reveal Cr-Mn intermetallic magnetic exchange constants, J, of 
      4.7 to -9.4 cm(-1) (H = -JS(Cr) x S(Mn)). It is observed that the
      antiferromagnetic interaction through the Mn-N-C-Cr bridge increases as the Mn-N
      C angle (theta) decreases to the range of 155-180 degrees, obeying an empirical
      relationship: J = -40 + 0.2theta. This result suggests that the best overlap
      between t(2g) (high-spin Mn(II)) and t(2g) (low-spin Cr(III)) occurs at an angle
      of approximately 155 degrees.

PMID- 15962961
TI  - X-ray absorption spectroscopic study of the reduced hydroxylases of methane
      monooxygenase and toluene/o-xylene monooxygenase: differences in active site
      structure and effects of the coupling proteins MMOB and ToMOD.
AB  - The diiron active sites of the reduced hydroxylases from methane monooxygenase
      (MMOH(red)) and toluene/o-xylene monooxygenase (ToMOH(red)) have been
      investigated by X-ray absorption spectroscopy (XAS). Results of Fe K-edge and
      extended X-ray absorption fine structure analysis reveal subtle differences
      between the hydroxylases that may be correlated to access of the active site. XAS
      data were also recorded for each hydroxylase in the presence of its respective
      coupling protein. MMOB affects the outer-shell scattering contributions in the
      diiron site of MMOH(red), whereas ToMOD exerts its main effect on the first-shell
      ligation of ToMOH(red); it also causes a slight decrease in the Fe-Fe separation.
      These results provide an initial step toward delineating the differences in
      structure and reactivity in bacterial multicomponent monooxygenase proteins.

PMID- 15962962
TI  - New polynuclear manganese clusters from the use of the hydrophobic carboxylate
      ligand 2,2-dimethylbutyrate.
AB  - The syntheses, structures, and magnetic properties are reported of
      [Mn12O12(O2CPe(t))16(MeOH)4] (4), [Mn6O2(O2CH2)(O2CPe(t))11(HO2CPe(t))2(O2CMe)]
      (5), [Mn9O6(OH)(CO3)(O2CPe(t))12(H2O)2] (6), and [Mn4O2(O2CPe(t))6(bpy)2] (7, bpy
      = 2,2'-bipyridine), where Pe(t) = tert-pentyl (Pe(t)CO2H = 2,2-dimethylbutyric
      acid). These complexes were all prepared from reactions of
      [Mn12O12(O2CPe(t))16(H2O)4] (3) in CH2Cl2. Complex 4 x 2MeCN crystallizes in the
      triclinic space group P1 and contains a central [Mn(IV)4O4] cubane core that is
      surrounded by a nonplanar ring of eight alternating Mn(III) and eight mu3-O(2-)
      ions. This is only the third Mn12 complex in which the four bound water molecules
      have been replaced by other ligands, in this case MeOH. Complex 5 x (1/2)CH2Cl2
      crystallizes in the monoclinic space group P2(1)/c and contains two [Mn3(mu3
      O)]7+ units linked at two of their apexes by two Pe(t)CO2(-) ligands and one mu4
      CH2O2(2-) bridge. The complex is a new structural type in Mn chemistry, and also
      contains only the third example of a gem-diolate unit bridging four metal ions.
      Complex 6 x H2O x Pe(t)CO2H crystallizes in the orthorhombic space group Cmc2(1)
      and possesses a [Mn(III)9(mu3-O)6(mu-OH)(mu3-CO3)]12+ core. The molecule contains
      a mu3-CO3(2-) ion, the first example in a discrete Mn complex. Complex 7 x 2H2O
      crystallizes in the monoclinic space group P2(1)/c and contains a known
      [Mn(III)2Mn(II)2(mu3-O)2]6+ core that can be considered as two edge-sharing,
      triangular [Mn3O] units. Additionally, the synthesis and magnetic properties of a
      new enneanuclear cluster of formula [Mn9O7(O2CCH2Bu(t))13(THF)2] (8, THF =
      tetrahydrofuran) are reported. The molecule was obtained by the reaction of
      [Mn12O12(O2CCH2Bu(t))16(H2O)4] (2) with THF. Complexes 2 and 4 display
      quasireversible redox couples when examined by cyclic voltammetry in CH2Cl2;
      oxidations are observed at -0.07 V (2) and -0.21 V (4) vs ferrocene. The magnetic
      properties of complexes 4-8 have been studied by direct current (DC) and
      alternating current (AC) magnetic susceptibility techniques. The ground-state
      spin of 4 was established by magnetization measurements in the 1.80-4.00 K and
      0.5-7 T ranges. Fitting of the reduced magnetization data by full matrix
      diagonalization, incorporating a full powder average and including only axial
      anisotropy, gave S = 10, g = 2.0(1), and D = -0.39(10) cm(-1). The complex
      exhibits two frequency-dependent out-of-phase AC susceptibility signals
      (chi(M)'') indicative of slow magnetization relaxation. An Arrhenius plot
      obtained from chi(M)'' vs T data gave an effective energy barrier to relaxation
      (U(eff)) of 62 and 35 K for the slower and faster relaxing species, respectively.
      These studies suggest that complex 4 is a single-molecule magnet (SMM). DC
      susceptibility studies on complexes 5-8 display overall antiferromagnetic
      behavior and indicate ground-state spin values of S < or = 2. AC susceptibility
      studies at < 10 K confirm these small values and indicate the population of low
      lying excited states even at these low temperatures. This supports the small
      ground-state spin values to be due to spin frustration effects.

PMID- 15962963
TI  - Model for acetylene reduction by nitrogenase derived from density functional
      theory.
AB  - The catalytic cycle of acetylene reduction at the FeMo cofactor of nitrogenase
      has been investigated on the basis of density functional theory. C2H2 binds to
      the same site as N2, but it binds to a less reduced state of the cofactor. In a
      manner similar to that of N2 binding, one of the sulfur bridges opens during
      acetylene binding. The model explains the strong noncompetitive inhibition of N2
      reduction by C2H2 and the weak competitive inhibition of C2H2 reduction by N2.
      Our proposed mechanism is consistent with experimentally observed
      stereoselectivity and the ability of C2H2 to suppress H2 production by
      nitrogenase.

PMID- 15962964
TI  - Crystal structure, chemical bonding, and phase relations of the novel compound
      Co4Al(7+x)Si(2-x) (0.27 < or = x < or = 1.05).
AB  - The title compound was detected and characterized during a systematic study of
      the Al-rich part of the Co-Al-Si system. The crystal structure was established
      via single-crystal X-ray diffraction. It represents a new type of structure of
      intermetallic compounds (Pearson symbol mC26, space group C2/m). The homogeneity
      range of the phase Co4Al(7+x)Si(2-x) (0.27(3) < or = x < or = 1.05(2)) and
      equilibria with neighboring phases were studied by electron probe microanalysis
      (EPMA) and X-ray powder diffraction. The lattice parameters of the compound were
      found to vary between Al-poor and Al-rich composition (a = 11.949(1)-12.042(1) A,
      b = 3.9986(4)-4.0186(4) A, c = 7.6596(8)-7.6637(9) A, and beta = 106.581(7)
      106.140(7) degrees). A partial disorder caused by the Al/Si substitution in one
      of the five main group element positions was found, and different ordering models
      yielding different Al/Si occupation motifs and different distributions of
      interatomic distances are discussed in detail. Chemical bonding analysis with the
      electron localization function (ELF) reveals a covalently bonded Al/Si network
      and rather ionic interactions between Co and the network.

PMID- 15962965
TI  - Synthesis and characterization of the face-sharing bioctahedral [Mo2O6F3]3-
      anion.
AB  - The face-sharing bioctahedral molybdenum(VI) oxide fluoride anion [Mo2O6F3]3- has
      been isolated in the new compound [Cu(3-apy)4]3(Mo2O6F3)2 (3-apy = 3
      aminopyridine) and has been characterized by experimental and computational
      techniques. Single-crystal X-ray diffraction studies show that the structure of
      the [Mo2O6F3]3- anion resembles two distorted face-sharing octahedra, each with
      three short terminal metal-ligand bonds and three long metal-ligand-metal
      bridging interactions. Aspects of the electronic structure, as well as geometric
      comparisons of the bond lengths and angles in [Mo2O6F3]3- with those in the
      similarly distorted [MoO3F3]3- anion, suggest that the six terminal ligand
      positions of the confacial bioctahedra are occupied exclusively by oxide ligands
      and that the three bridging sites are occupied by fluorides. Crystal data for
      [Cu(3-apy)4]3(Mo2O6F3)2: trigonal space group R3 (No. 148) with hexagonal axes of
      a = 13.881(1) A and c = 31.783(3) A (Z = 3).

PMID- 15962966
TI  - Dual room-temperature fluorescent and phosphorescent emission in 8-quinolinolate
      osmium(II) carbonyl complexes: rationalization and generalization of intersystem
      crossing dynamics.
AB  - A new series of quinolinolate osmium carbonyl complexes were synthesized and
      characterized by spectroscopic methods. Single-crystal X-ray diffraction studies
      indicate that these complexes consist of an octahedral ligand arrangement with
      one chelating quinolinolate, one tfa or halide ligand, and three mutually
      orthogonal terminal CO ligands. Variation of the substituents on quinolinolate
      ligands imposes obvious electronic or structural effects, while changing the tfa
      ligand to an electron-donating iodide slightly increases the charge density on
      the central osmium atom. These Os(II) complexes show salient dual emissions
      consisting of fluorescence and phosphorescence, the spectral properties and
      relaxation dynamics of which have been studied comprehensively. The results, in
      combination with the theoretical approaches, lead us to propose that the emission
      mainly originates from the quinolinolate pi pi* state. Both experimental and
      theoretical approaches generalize various types of intersystem crossing versus
      those of the tris(quinolinolate) iridium Ir(Q)3, and their relative efficiencies
      were accessed on the basis of the associated frontier orbital configurations. Our
      results suggest that [1d(pi)pi* absolute value(H(so))3 pi pi*] (or [3d(pi)pi*
      absolute value(H(so))1 pi pi*]) in combination with a smaller deltaE(S1-T1) gap
      (i.e., increasing the MLCT (d(pi)pi*) character) is the main driving force to
      induce the ultrafast S1 --> T1 intersystem crossing in the third-row transition
      metal complexes, giving the strong phosphorescent emission.

PMID- 15962967
TI  - Assembly of helical hydrogen bonds in a new layered aluminophosphate
      [C6N3H17][Al2(HPO4)(PO4)2].
AB  - A new layered aluminophosphate, [C6N3H17][Al2(HPO4)(PO4)2] (denoted AlPO-CJ21),
      has been prepared in an alcoholic system by the use of N-(2-aminoethyl)
      piperazine (AEPP) as the template. Its inorganic layer containing a series of
      bridged six-membered rings (MRs) is a new type of 4.6-net sheet built up from
      AlO4, PO2(OH)(=O), and PO3(=O) tetrahedra. Interestingly, inorganic helical
      chains of right- or left-handedness are presented in the aluminophosphate layers,
      and fascinating hydrogen-bonded helices are self-assembled under solvothermal
      conditions between organic templates and inorganic sheets via strong hydrogen
      bondings of O...N atoms. Crystal data: monoclinic, P2(1) (No. 4), a = 10.069(2)
      A, b = 8.0875(16) A, c = 10.598(2) A, beta = 94.71(3) degrees, z = 2, R(1) =
      0.0325 [I > 2sigma(I)], and wR(2) = 0.0807 (all data); Flack parameter: 0.03.

PMID- 15962968
TI  - Synthesis, structure, and stereochemistry of trinuclear metal complexes formed
      from the phosphorus-based achiral tripodal ligand {P(S)[N(Me)N=CHC6H4-o-OH]3}
      (LH3): luminescent properties of L2Cd3 x 2H2O.
AB  - Neutral trinuclear metal complexes L2Cd3 x 2H2O, L2Mn3 x MeOH, and L2Zn3 x MeOH
      were isolated in the reaction between the phosphorus-centered achiral
      tris(hydrazone) P(S)[N(Me)N=CHC6H(4)-o-OH]3 (LH3) and the corresponding divalent
      metal ions. The trinuclear complexes contain two equivalent terminal metal ions
      (M(t)) and a central metal ion (M(c)). The ligand encapsulates M(t) in a facial
      N3O3 coordination environment. From the coordination sphere of the two terminal
      metal ions a pair of phenolic oxygen atoms further coordinate to the central
      metal ion. The coordination requirements of M(c) are completed by the solvents of
      coordination. The achiral trianionic tripodal ligand (L)3- induces chirality in
      the metal complexes. This results in a delta (clockwise) or lambda
      (anticlockwise) configuration for the terminal metal ions. The enantiomeric
      complexes 2-4 (delta-delta or lambda-lambda) crystallize as racemic compounds.
      The supramolecular structures of 2-4 reveal chiral recognition in the solid
      state; every molecule with the delta-delta configuration interacts
      stereospecifically, through C-H...S=P bonds, with two lambda-lambda molecules to
      generate a one-dimensional polymeric chain. Photophysical studies of the
      diamagnetic trinuclear complexes reveal that the tricadmium complex is
      luminescent in the solid state as well as in solution. In contrast LH3 and L2Zn3
      x MeOH are nonluminescent.

PMID- 15962969
TI  - Synthesis and molecular and extended structures for a diaminonaphthalene-derived
      bis(amido)stannylene.
AB  - The cyclic bis(amido)tin(II) compound Sn[1,8-((iPrN)2C10H6] (2) was isolated from
      the reaction of Li2[1,8-((iPrN)2C10H6] (1) and SnCl2. Solid-state structural
      analysis of 2 showed it to be a mononuclear species with a pyramidal Sn center as
      part of a nonplanar metallaheterocycle. The packing diagram of 2 revealed an
      extended one-dimensional head-to-tail chain structure with short intermolecular
      Sn/arene-C interactions. Computational examination of 2 (DFT/PW91 and MP2 with 6
      31G* and 6-311G** basis functions) indicated that the optimum gas-phase structure
      of 2,which displays a Sn center in the plane of the naphthyl backbone with a
      slightly twisted metallaheterocycle, is approximately 24 kcal/mol lower in energy
      than the X-ray structure. The solid-state geometry of 2 is attributed to the
      intermolecular donation of the naphthalene pi-electrons to a Lewis acidic Sn
      center, which leads to the observed supramolecular structure. The crystal
      structure of 1 is also reported.

PMID- 15962970
TI  - Effective, selective coupling of propylene oxide and carbon dioxide to
      poly(propylene carbonate) using (salen)CrN3 catalysts.
AB  - The copolymerization of propylene oxide and CO2 has been investigated employing
      Cr(salen)N3 complexes as catalysts. Unfortunately the reaction could not be
      studied in real time via in situ IR spectroscopy, thereby obtaining detailed
      kinetic data, because of the copolymer limited solubility in most solvents.
      Investigations employing batch reactor runs concentrating on varying the
      cocatalyst, the equivalents of cocatalyst, and the steric and electronic
      structure of the catalyst through modification of the salen ligand were
      undertaken. It was discovered that the optimal catalyst for copolymer selectivity
      vs the monomeric propylene carbonate was one that contained a salen ligand with
      an electron-withdrawing phenylene backbone and electron-donating tert-butyl
      groups in the phenolate rings. This catalyst was used to investigate the effect
      of altering the nature of the cocatalyst and its concentration, the three
      cocatalysts being tricyclohexylphosphine (PCy3), PPN+ N3(-), and PPN+ Cl-, where
      PPN+ is the large very weakly interacting bis(triphenylphosphoramylidene)ammonium
      cation. By utilization of more or less than 1 equiv of PCy3 as cocatalyst, the
      yield of polymer was reduced. On the other hand, the PPN+ salts showed the best
      activity when 0.5 equiv was employed, and produced only cyclic when using over 1
      equiv.

PMID- 15962971
TI  - Enantiomerically pure pentagonal-bipyramidal metal complexes with predetermined
      helicity in the solid and solution states.
AB  - New metal complexes with pentagonal-bipyramidal geometry have been synthesized
      with the chiral, pentadentate bis(oxazoline) ligand (R,R)-1, including the metal
      ions magnesium(II), iron(II), and cadmium(II). In the solid state, a complete
      transfer of chirality from the ligand is observed to exclusively yield
      enantiomerically pure P-helical, isostructural pentagonal bipyramidal complexes,
      as determined by X-ray analysis of four compounds. This uncommon coordination
      geometry is likely to be driven by pi-pi-stacking of the terminal phenyl groups
      of the linear ligands. The complex cations in [Fe((R,R)-1)(H2O)2](ClO4)2 (3),
      [Cd((R,R)-1)(H2O)2](ClO4)2 (4), and [Mg((R,R)-1)(H2O)2](ClO4)2 (5) are
      mononuclear with the two apical positions of the pentagonal bipyramide occupied
      by two water molecules. In contrast, the structure in dinuclear [Cd((R,R)
      1)(MeOH)(mu-I)(CdI3)] (2c) can be described as pentagonal-bipyramidal around
      cadmium with MeOH and distorted-tetrahedral CdI4 (via one bridging iodo ligand)
      completing the coordination sphere in axial positions. The crystal packing of 3-5
      shows a highly ordered orientation of the mononuclear helical cations into one
      dimensional chains along the crystallographic axis a, stabilized by
      intermolecular pi-pi-stacking. In contrast, the dinuclear helices in 2c are
      tilted relative to one another, and consequently, directed, one-dimensional
      helicity in the solid state is not observed. Studies using a combination of mass
      spectrometry and NMR and CD spectroscopy indicate the presence of only one C2
      symmetrical, mononuclear species in acetonitrile for each case, suggesting the
      formation of diastereo- and enantiomerically pure complexes also in the solution
      state. All compounds exhibit a very characteristic and almost identical CD
      pattern between 200 nm and 300 nm. This signal can be attributed to the P
      helical, pentagonal arrangement of the ligand.

PMID- 15962972
TI  - Geometrical and electronic structures of dinuclear complex ions {(mu
      bpym)[Cu(EAr3)2]2}2+ with intramolecular "organic sandwich" formation (E = P or
      As; Ar = Aryl; bpym = 2,2'-bipyrimidine).
AB  - The compound {(mu-bpym)[Cu(AsPh3)2]2}(BF4)2 (1) has been prepared and studied in
      comparison with the triphenylphosphine analogue 2. Qualitatively, the structure
      of 1 with characteristically distorted copper(I) coordination caused by
      Ph/bpym/Ph sandwich interactions is similar to that of 2 and is approximately
      reproduced by DFT calculations for the model complex ions {(mu
      bpym)[Cu(EMe2Ph)2]2}2+, E = P or As. In contrast, the dinuclear {(mu-bpym)[Cu(P(3
      Me-C6H4)3)2]2}(BF4)2 (3) displays a distinctly less distorted metal coordination
      geometry due to the steric requirements of the methyl groups in the meta-tolyl
      substituents. The electrochemical reduction of 1 is less reversible than for the
      phosphine analogues; the one-electron-reduced form 1*- exhibits a broad,
      unresolved EPR signal at g = 2.0023. Resonance Raman spectroscopy of 1 shows the
      typical vibrations of the bpym ligand in agreement with the MLCT assignment of
      the long-wavelength transitions below 500 nm. All three dinuclear complexes
      exhibit luminescence at room temperature in the solid and in solution.

PMID- 15962973
TI  - Structural, magnetic, and spectroscopic comparative studies on four new
      derivatives of DIMMAL (2-di1H-2-imidazolylmethylmalonate): a novel generator of
      multidimensional networks.
AB  - This paper reports the synthesis, structure solution, and magnetic
      characterization of four new DIMMAL-containing compounds (H2DIMMAL = 2-di1H-2
      imidazolylmethylmalonic acid), H2DIMMAL x H2O (1), Na2(DIMMAL) x 5H2O (2),
      [Cu(HDIMMAL)2] (3), and [Cu2(DIMMAL)2(H2O)2] x 2H2O (4). Compound 1, containing
      two carboxylates and two protonated imidazole rings, adopts the dizwitterion
      configuration. These monohydrate MBBs pack together into a 3D array driven, as in
      the other three cases herein reported, by a combination of multiple-path H-bonds
      and aromatic-aromatic interactions. Compound 2 consists of centrosymmetric Na+
      tetramers in which four NaO6 distorted octahedra are interconnected by
      carboxylate and water bridges. Compound 3 consists of mononuclear [Cu(HDIMMAL)2]
      units in which HDIMMAL- acts as a tridentate ligand through two imidazole N atoms
      and the deprotonated O from a carboxylate. Compound 4 consists of centrosymmetric
      cyclic dinuclear [Cu2(DIMMAL)2(H2O)2] x 2H2O units involving propionate-arm
      bridges. The building-block units described above, in each case, are
      interconnected into 3D networks by multiple H-bonding paths and aromatic-aromatic
      interactions. The EPR spectra are indicative of an essentially d(x2-y2) ground
      state for the copper(II) ions in 3 and 4 (CuN4O2 and CuN2O2O' chromophores,
      respectively). Magnetic susceptibility measurements in the range of 1.8-200 K for
      compound 4 show weak antiferromagnetic exchange between the copper(II) ions (2J =
      -1.6(1) cm(-1)). The effectiveness of the propionate-arm bridges, involving C-C
      sigma bonds, in propagating magnetic exchange between the copper(II) ions is
      discussed.

PMID- 15962974
TI  - Structural and photophysical properties of coordination networks combining
      [Ru(bipy)(CN)4]2- anions and lanthanide(III) cations: rates of photoinduced Ru-to
      lanthanide energy transfer and sensitized near-infrared luminescence.
AB  - Co-crystallization of K2[Ru(bipy)(CN)4] with lanthanide(III) salts (Ln = Pr, Nd,
      Gd, Er, Yb) from aqueous solution affords coordination oligomers and networks in
      which the [Ru(bipy)(CN)4]2- unit is connected to the lanthanide cation via Ru-CN
      Ln bridges. The complexes fall into two structural types:
      [{Ru(bipy)(CN)4}2{Ln(H2O)m}{K(H2O)n}] x xH2O (Ln = Pr, Er, Yb; m = 7, 6, 6,
      respectively), in which two [Ru(bipy)(CN)4]2- units are connected to a single
      lanthanide ion by single cyanide bridges to give discrete trinuclear fragments,
      and [{Ru(bipy)(CN)4}3{Ln(H2O)4}2] x xH2O (Ln = Nd, Gd), which contain two
      dimensional sheets of interconnected, cyanide-bridged Ru2Ln2 squares. In the Ru
      Gd system, the [Ru(bipy)(CN)4]2- unit shows the characteristic intense (3)metal
      to-ligand charge transfer luminescence at 580 nm with tau = 550 ns; with the
      other lanthanides, the intensity and lifetime of this luminescence are diminished
      because of a Ru --> Ln photoinduced energy transfer to low-lying emissive states
      of the lanthanide ions, resulting in sensitized near-infrared luminescence in
      every case. From the degree of quenching of the Ru-based emission, Ru --> Ln
      energy-transfer rates can be estimated, which are in the order Yb (k(EnT)
      approximately 3 x 10(6) sec(-1), the slowest energy transfer) < Er < Pr < Nd
      (k(EnT) approximately 2 x 10(8) sec(-1), the fastest energy transfer). This order
      may be rationalized on the basis of the availability of excited f-f levels on the
      lanthanide ions at energies that overlap with the Ru-based emission spectrum. In
      every case, the lifetime of the lanthanide-based luminescence is short
      (tens/hundreds of nanoseconds, instead of the more usual microseconds), even when
      the water ligands on the lanthanide ions are replaced by D2O to eliminate the
      quenching effects of OH oscillators; we tentatively ascribe this quenching effect
      to the cyanide ligands.

PMID- 15962975
TI  - Tetraphosphinite resorcinarene complexes: silver(I) capsule complexes.
AB  - Resorcinarene tetraphosphinite ligands, P4, react with silver(I) trifluoroacetate
      or silver(I) triflate, AgX, to give the corresponding [Ag4X4(P4)] complexes. The
      resorcinarene skeleton in these complexes adopts a boat conformation with the
      silver(I) phosphinite units on the horizontal, rather than the upright, arene
      units of the resorcinarene. The [Ag4X4(P4)] complexes react with free P4 ligand
      to yield the [Ag2X2(P4)] or [AgX(P4)] complexes, which are characterized in
      solution by NMR spectroscopy to have a conformation opposite to that of the
      [Ag4X4(P4)] complexes; the silver(I) phosphinite groups are on the upright arene
      rings of the resorcinarene "boat" instead of the horizontal arene units. There is
      an easy equilibrium between these complexes. When X = triflate, the [Ag4X4(P4)]
      complexes disproportionate and add aqua ligands during slow crystallization to
      give "capsule complexes", which are characterized crystallographically as
      [Ag10(O3SCF3)10(OH2)6(P4)2], [Ag10(O3SCF3)6(OH2)8(P4)2][O3SCF3]4, or
      [Ag13(O3SCF3)13(OH2)7(P4)2] depending on the resorcinarene tetraphosphinite
      ligand P4 used. These unusual capsule complexes are formed by the tail-to-tail
      self-assembly of pairs of [Ag4(P4)]4+ units linked by additional silver ions that
      bind to the phenyl substituents of one resorcinarene through {Ag(eta2-C6H5)}+
      binding and to the bridging triflate ligands, aqua ligands, or both of the other
      resorcinarene unit.

PMID- 15962976
TI  - Synthesis and characterization of new coordination polymers generated from bent
      bis(cyanophenyl)oxadiazole ligands and Ag(I) salts.
AB  - Two new bent bis(cyanophenyl)oxadiazole ligands, 2,5-bis(4-cyanophenyl)-1,3,4
      oxadiazole (L7) and 2,5-bis(3-cyanophenyl)-1,3,4-oxadiazole (L8), were
      synthesized. The coordination chemistry of these ligands with various Ag(I) salts
      has been investigated. Seven new coordination polymers, namely,
      {[Ag(L7)(H2O)]ClO4}n) (1) (triclinic, P1, a = 9.342(4) A, b = 9.889(4) A, c =
      10.512(4) A, alpha = 68.978(6) degrees, beta = 78.217(6) degrees, gamma =
      81.851(7) degrees, Z = 2), {[Ag(L7)]SO3CF3}n (2) (monoclinic, P2(1)/n, a =
      7.559(2) A, b = 23.739(6) A, c = 10.426(3) A, beta = 108.071(4) degrees, Z = 4),
      {[Ag(L8)]BF4 x 0.5(C6H6) x H2O}n (3) (triclinic, P1, a = 7.498(3) A, b =
      10.649(4) A, c = 13.673(5) A, alpha = 98.602(5) degrees, beta = 100.004(5)
      degrees, gamma =110.232(5) degrees, Z = 2), {[Ag(L8)SbF6] x H2O}n (4) (triclinic,
      P1, a = 8.2621(9) A, b = 10.6127(12) A, c = 13.3685(15) A, alpha = 98.012(2)
      degrees, beta = 106.259(2) degrees, gamma = 112.362(2) degrees, Z = 2),
      {[Ag2(L8)2(SO3CF3)] x H2O}n (5) (triclinic, P1, a = 10.713(4) A, b = 13.449(5) A,
      c = 15.423(5) A, alpha = 65.908(5) degrees, beta = 74.231(5) degrees, gamma =
      83.255(5) degrees, Z = 2), {[Ag2(L8)(C6H6)(ClO4)] x ClO4}n (6) (monoclinic,
      P2(1)/n, a = 6.9681(17) A, b = 20.627(5) A, c = 17.437(4) A, beta = 95.880(4)
      degrees, Z = 4), and {[Ag2(L8)(H2PO4)2]}n (7) (triclinic, P1, a = 7.956(2) A, b =
      9.938(3) A, c = 14.242(4) A, alpha = 106.191(4) degrees, beta = 97.322(4)
      degrees, gamma = 107.392(4) degrees, Z = 1), were obtained by the combination of
      L7 and L8 with Ag(I) salts in a benzene/methylene chloride mixed-solvent system
      and fully characterized by infrared spectroscopy, elemental analysis, and single
      crystal X-ray diffraction. In addition, the luminescence and electrical
      conductance properties of compounds 1-6 and the host-guest chemistry of compound
      3 were investigated.

PMID- 15962977
TI  - Light-driven expulsion of the sterically hindering ligand L in tris-diimine
      ruthenium(II) complexes of the Ru(phen)2(L)2+ family: a pronounced ring effect.
AB  - Three new ruthenium(II) complexes have been prepared which contain two 1,10
      phenanthroline units and a third sterically hindering chelate. In one case, the
      hindering ligand is a disubstituted 2,2'-bipyridine (bpy) attached to two very
      bulky manisyl groups. The two other systems are similar in terms of size of the
      hindering groups (anisyl substituents) located close to the central metal. The
      complexes investigated in the Present Report are aimed at providing building
      blocks of future light-driven molecular machines. The photochemical expulsion of
      the sterically hindering chelate has thus been studied by UV-vis spectroscopy and
      1H NMR. Surprisingly, the manisyl-containing complex turned out to be
      photochemically inert, indicating that a too bulky group acts as a protecting
      function versus decomplexation rather than as a destabilizing group. For the two
      other systems, a pronounced ring effect was observed: whereas the acyclic systems
      undergo fast photochemical expulsion of the bipy-based ligand, in the cyclic
      complex, the bipy-incorporating ring is decoordinated about 5 times less
      efficiently than the acyclic ligand of the previous case. These observations on
      the strong dependence of the photochemical behavior of the ruthenium(II)
      complexes on their structural properties are corroborated by X-ray diffraction
      studies on the three compounds investigated.

PMID- 15962978
TI  - Tuning the band gap in hybrid tin iodide perovskite semiconductors using
      structural templating.
AB  - Structural distortions within the extensive family of organic/inorganic hybrid
      tin iodide perovskite semiconductors are correlated with their experimental
      exciton energies and calculated band gaps. The extent of the in- and out-of-plane
      angular distortion of the SnI4(2-) perovskite sheets is largely determined by the
      relative charge density and steric requirements of the organic cations. Variation
      of the in-plane Sn-I-Sn bond angle was demonstrated to have the greatest impact
      on the tuning of the band gap, and the equatorial Sn-I bond distances have a
      significant secondary influence. Extended Huckel tight-binding band calculations
      are employed to decipher the crystal orbital origins of the structural effects
      that fine-tune the band structure. The calculations suggest that it may be
      possible to tune the band gap by as much as 1 eV using the templating influence
      of the organic cation.

PMID- 15962979
TI  - Rodlike bimetallic ruthenium and osmium complexes bridged by phenylene spacers.
      Synthesis, electrochemistry, and photophysics.
AB  - In the search for light-addressable nanosized compounds we have synthesized 10
      dinuclear homometallic trisbipyridyl complexes of linear structure with the
      general formula [M(bpy)3-BL-M(bpy)3]4+ [M = Ru(II) or Os(II); BL = polyphenylenes
      (2, 3, 4, or 5 units) or indenofluorene; bpy = 2,2'-bipyridine]. By using a
      "chemistry on the complex" approach, different sizes of rodlike systems have been
      obtained with a length of 19.8 and 32.5 A for the shortest and longest complex,
      respectively. For one of the ruthenium precursors, [Rubpy-ph2-Si(CH3)3][PF6]2,
      single crystals were obtained by recrystallization from methanol. Their
      photophysical and electrochemical properties are reported. All the compounds are
      luminescent both at room and low temperature with long excited-state lifetimes
      due to an extended delocalization. Nanosecond transient absorption showed that
      the lowest excited state involves the chelating unit attached to the bridging
      ligand. Electrochemical data indicated that the first reduction is at a slightly
      more positive potential than for the reference complexes [M(bpy)3]2+ (M = Ru,
      Os). This result confirms that the best acceptor is the bipyridine moiety
      connected to the conjugated spacers. The role of the tilt angle between the
      phenylene units, in the two series of complexes, for the ground and excited
      states is discussed.

PMID- 15962981
TI  - Assembly of azido- or cyano-bridged binuclear complexes containing the bulky
      [Mn(phen)2]2+ building block: syntheses, crystal structures, and magnetic
      properties.
AB  - Two new cyano-bridged heterobinuclear complexes,
      [Mn(II)(phen)2Cl][Fe(III)(bpb)(CN)2] x 0.5CH3CH2OH x 1.5H2O (1) and
      [Mn(II)(phen)2Cl][Cr(III)(bpb)(CN)2] x 2H2O (2) [phen = 1,10-phenanthroline;
      bpb(2-) = 1,2-bis(pyridine-2-carboxamido)benzenate], and four novel azido-bridged
      Mn(II) dimeric complexes, [Mn2(phen)4(mu(1,1)-N3)2][M(III)(bpb)(CN)2]2 x H2O [M =
      Fe (3), Cr (4), Co (5)] and [Mn2(phen)4(mu(1,3)-N3)(N3)2]BPh4 x 0.5H2O (6), have
      been synthesized and characterized by single-crystal X-ray diffraction analysis
      and magnetic studies. Complexes 1 and 2 comprise [Mn(phen)2Cl]+ and [M(bpb)(CN)2]
      units connected by one cyano ligand of [M(bpb)(CN)2]-. Complexes 3-5 are doubly
      end-on (EO) azido-bridged Mn(II) binuclear complexes with two [M(bpb)(CN)2]-
      molecules acting as charge-compensating anions. However, the Mn(II) ions in
      complex 6 are linked by a single end-to-end (EE) azido bridging ligand with one
      large free BPh4(-) group as the charge-balancing anion. The magnetic coupling
      between Mn(II) and Fe(III) or Cr(III) in complexes 1 and 2 was found to be
      antiferromagnetic with J(MnFe) = -2.68(3) cm(-1) and J(MnCr) = -4.55(1) cm(-1) on
      the basis of the Hamiltonian H = -JS(Mn)S(M) (M = Fe or Cr). The magnetic
      interactions between two Mn(II) ions in 3-5 are ferromagnetic in nature with the
      magnetic coupling constants of 1.15(3), 1.05(2), and 1.27(2) cm(-1) (H = 
      JS(Mn1)S(Mn2)), respectively. The single EE azido-bridged dimeric complex 6
      manifests antiferromagnetic interaction with J = -2.29(4) cm(-1) (H = 
      JS(Mn1)S(Mn2)). Magneto-structural correlationship on the EO azido-bridged Mn(II)
      dimers has been investigated.

PMID- 15962980
TI  - The reactions of nitrosyl complexes with cysteine.
AB  - The reaction kinetics of a set of ruthenium nitrosyl complexes, {(X)5MNO}n,
      containing different coligands X (polypyridines, NH3, EDTA, pz, and py) with
      cysteine (excess conditions), were studied by UV-vis spectrophotometry, using
      stopped-flow techniques, at an appropriate pH, in the range 3-10, and T = 25
      degrees C. The selection of coligands afforded a redox-potential range from -0.3
      to +0.5 V (vs Ag/AgCl) for the NO+/NO bound couples. Two intermediates were
      detected. The first one, I1, appears in the range 410-470 nm for the different
      complexes and is proposed to be a 1:1 adduct, with the S atom of the cysteinate
      nucleophile bound to the N atom of nitrosyl. The adduct formation step of I1 is
      an equilibrium, and the kinetic rate constants for the formation and dissociation
      of the corresponding adducts were determined by studying the cysteine
      concentration dependence of the formation rates. The second intermediate, I2, was
      detected through the decay of I1, with a maximum absorbance at ca. 380 nm. From
      similar kinetic results and analyses, we propose that a second cysteinate adds to
      I1 to form I2. By plotting ln k1(RS-) and ln k2(RS-) for the first and second
      adduct formation steps, respectively, against the redox potentials of the NO+/NO
      couples, linear free energy plots are obtained, as previously observed with OH-
      as a nucleophile. The addition rates for both processes increase with the
      nitrosyl redox potentials, and this reflects a more positive charge at the
      electrophilic N atom. In a third step, the I2 adducts decay to form the
      corresponding Ru-aqua complexes, with the release of N2O and formation of
      cystine, implying a two-electron process for the overall nitrosyl reduction. This
      is in contrast with the behavior of nitroprusside ([Fe(CN)5NO]2-; NP), which
      always yields the one-electron reduction product, [Fe(CN)5NO]3-, either under
      substoichiometric or in excess-cysteine conditions.

PMID- 15962982
TI  - Syntheses and properties of emissive iridium(III) complexes with tridentate
      benzimidazole derivatives.
AB  - A series of novel emissive Ir(III) complexes having the coordination environments
      of [Ir(N--N--N)2]3+, [Ir(N--N--N)(N--N)Cl]2+, and [Ir(N--N--N)(N--C--N)]2+ with
      2,6-bis(1-methyl-benzimidazol-2-yl)pyridine (L1, N--N--N), 1,3-bis(1-methyl
      benzimidazol-2-yl)benzene (L2H, N--C--N), 4'-(4-methylphenyl)-2,2':6',2' '
      terpyridine (ttpy, N--N--N), and 2,2'-bipyridine (bpy, N--N) have been
      synthesized and their photophysical and electrochemical properties studied. The
      Ir(III) complexes exhibited phosphorescent emissions in the 500-600 nm region,
      with lifetimes ranging from approximately 1-10 micros at 295 K. Analysis of the 0
      0 energies and the redox potentials indicated that the lowest excited state of
      [Ir(L1)(L2)]2+ possessed the highest contribution of 3MLCT (MLCT = metal-to
      ligand charge transfer) among the Ir(III) complexes, reflecting the sigma
      donating ability of the tridentate ligand, ttpy < L1 < L2. The emission quantum
      yields (phi) of the Ir(III) complexes ranged from 0.037 to 0.19, and the highest
      phi value (0.19) was obtained for [Ir(L1)(bpy)Cl]2+. Radiative rate constants
      (k(r)) were 1.2 x 10(4) s(-1) for [Ir(ttpy)2]3+, 3.7 x 10(4) s(-1) for
      [Ir(L1)(bpy)Cl]2+, 3.8 x 10(4) s(-1) for [Ir(ttpy)(bpy)Cl]2+, 3.9 x 10(4) s(-1)
      for [Ir(L1)2]3+, and 6.6 x 10(4) s(-1) for [Ir(L1)(L2)]2+. The highest radiative
      rate for [Ir(L1)(L2)]2+ with the highest contribution of 3MLCT could be explained
      in terms of the singlet-triplet mixing induced by spin-orbit coupling of 5d
      electrons in the MLCT electronic configurations.

PMID- 15962983
TI  - Dinuclear, bishydrated Gd(III) polyaminocarboxylates with a rigid xylene core
      display remarkable proton relaxivities.
AB  - Two novel dinuclear Gd(III) complexes have been synthesized, based on a xylene
      core substituted with diethylenetriamine-N,N,N'',N''-tetraacetate (DTTA)
      chelators in para or meta position. The complexes [Gd2(pX(DTTA)2)(H2O)4]2- and
      [Gd2(mX(DTTA)2)(H2O)4]2- both exhibit high complex stability (log K(GdL) = 19.1
      and 17.0, respectively), and a good selectivity for Gd(III) against Zn(II), the
      most abundant endogenous metal ion (log K(ZnL) = 17.94 and 16.19). The water
      exchange rate is identical within experimental error for the two isomers:
      k(ex)298 = (9.0 +/- 0.4) x 10(6) s(-1) for [Gd2(pX(DTTA)2)(H2O)4]2- and (8.9 +/-
      0.5) x 10(6) s(-1) for [Gd2(mX(DTTA)2)(H2O)4]2-. It is very similar to the
      k(ex)298 of the structural analogue, bishydrated [Gd(TTAHA)(H2O)2]3-, and about
      twice as high as that of the monohydrated [Gd(DTPA)(H2O)]2- (TTAHA(6-) = N-tris(2
      aminoethyl)amine-N',N',N'',N'',N''',N'''-hexaacetate; DTPA(5-) =
      diethylenetriamine-N,N,N',N'',N''-pentaacetate). This relatively fast water
      exchange can be related to the presence of two inner sphere water molecules which
      decrease the stereorigidity of the inner sphere thus facilitating the water
      exchange process. At all frequencies, the water proton relaxivities (r1 = 16.79
      and 15.84 mM(-1) s(-1) for the para and meta isomers, respectively; 25 degrees C
      and 20 MHz) are remarkably higher for the two dinuclear chelates than those of
      mononuclear commercial contrast agents or previously reported dinuclear Gd(III)
      complexes. This is mainly the consequence of the two inner-sphere water
      molecules. In addition, the increased molecular size as compared to monomeric
      compounds associated with the rigid xylene linker between the two Gd(III)
      chelating subunits also contributes to an increased relaxivity. However, proton
      relaxivity is still limited by fast molecular motions which also hinder any
      beneficial effect of the increased water exchange rate.

PMID- 15962984
TI  - Controlled hydrolysis of lanthanide complexes of the N-donor tripod tris(2
      pyridylmethyl)amine versus bisligand complex formation.
AB  - The reaction of the lanthanide salts LnI3(thf)4 and Ln(OTf)3 with tris(2
      pyridylmethyl)amine (tpa) was studied in rigorously anhydrous conditions and in
      the presence of water. Under rigorously anhydrous conditions the successive
      formation of mono- and bis(tpa) complexes was observed on addition of 1 and 2
      equiv of ligand, respectively. Addition of a third ligand equivalent did not
      yield additional complexes. The mono(tpa) complex [Ce(tpa)I3] (1) and the
      bis(tpa) complexes [Ln(tpa)2]X3 (X = I, Ln = La(III) (2), Ln = Ce(III) (3), Ln =
      Nd(III) (4), Ln = Lu(III) (5); X = OTf, Ln = Eu(III) (6)) were isolated under
      rigorously anhydrous conditions and their solid-state and solution structures
      determined. In the presence of water, 1H NMR spectroscopy and ES-MS show that the
      successive addition of 1-3 equiv of tpa to triflate or iodide salts of the
      lanthanides results in the formation of mono(tpa) aqua complexes followed by
      formation of protonated tpa and hydroxo complexes. The solid-state structures of
      the complexes [Eu(tpa)(H2O)2(OTf)3] (7), [Eu(tpa)(mu-OH)(OTf)2]2 (8), and
      [Ce(tpa)(mu-OH)(MeCN)(H2O)]2I4 (9) have been determined. The reaction of the
      bis(tpa) lanthanide complexes with stoichiometric amounts of water yields a
      facile synthetic route to a family of discrete dimeric hydroxide-bridged
      lanthanide complexes prepared in a controlled manner. The suggested mechanism for
      this reaction involves the displacement of one tpa ligand by two water molecules
      to form the mono(tpa) complex, which subsequently reacts with the noncoordinated
      tpa to form the dimeric hydroxo species.

PMID- 15962985
TI  - New approach to the chemistry of technetium(V) and rhenium(V) phenylimido
      complexes: novel [M(NPh)PNP]3+ metal fragments (M = Tc, Re; PNP =
      aminodiphosphine) suitable for the synthesis of stable mixed-ligand compounds.
AB  - Ligand-exchange reactions of the aminodiphosphine ligand bis[(2
      diphenylphosphino)ethyl]amine hydrochloride (PNHP x HCl) with labile
      M(NPh)Cl3(PPh3)2 precursors (M = Re, Tc) in the presence of triethylamine yield
      monocationic phenylimido mer,cis-[M(NPh)Cl2(PNHP)]Cl (M = Re, 1; Tc, 2)
      intermediate complexes. X-ray analyses show that in both compounds the
      aminodiphosphine acts as a tridentate ligand dictating a mer,cis arrangement. Two
      chloride ligands, respectively in an equatorial and in the axial position trans
      to the linear M-NPh moiety, fill the remaining positions in a distorted
      octahedral geometry. The chloride trans to the metal-imido core is labile, and is
      replaced by an alcoholate group, without affecting the original geometry, as
      established in mer,cis-[Re(NPh)(OEt)Cl(PNHP)]Cl 4. Otherwise, ligand-exchange
      reactions involving the aminodiphosphine bis[(2
      diphenylphosphino)ethyl]methylamine (PNMeP), in which the central secondary amine
      has been replaced by a tertiary amine function, or its hydrochloride salt (PNMeP
      x HCl) give rise to three different species, depending on the experimental
      conditions: fac,cis-[Re(NPh)Cl2(PNMeP)]Cl 3a, cis,fac-Re(NPh)Cl3(PNMeP) x HCl 3b,
      and mer,trans-[Re(NPh)Cl2(PNMeP)]Cl 3c, which are characterized in solution by
      multinuclear NMR studies. The monodentate groups incorporated in these
      intermediate compounds, either halides and/or ethoxide, undergo substitution
      reactions with bidentate donor ligands such as catechol, ethylene glycol, and 1,2
      aminophenol to afford stable mixed ligand complexes of the type [M(NPh)(O,O
      cat)(PNP)]Cl [PNP = PNHP M = Re 5, Tc 6; PNP = PNMeP M = Re 7], [Re(NPh)(O,O
      gly)(PNP)]Cl [PNP = PNHP 8, PNMeP 9] and [Re(NPh)(O,N-ap)(PNMeP)]Cl 10. X-ray
      diffraction analyses of the representative compounds 5 and 8 reveal that the
      aminodiphosphine switches from the meridional to the facial coordination mode
      placing the heteroatom of the diphosphine trans to the phenylimido unit and the
      bidentate ligand in the equatorial plane. Solution-state NMR studies suggest an
      analogous geometry for 6, 7, 9, and 10. Comparison with similar mixed ligand
      complexes including the terminal nitrido group is discussed.

PMID- 15962986
TI  - Arylzinc alkoxides: [ArZnOCHPr(i)2]2 and Ar2Zn3(OCHPr(i)2)4 when Ar = C6H5, p
      CF3C6H4, 2,4,6-Me3C6H2, and C6F5.
AB  - From the reactions between diarylzinc compounds (Ar2Zn) and the alcohol
      (Pr(i)2CHOH) in toluene, the compounds [ArZn(OCHPr(i)2)]2 (Ar = C6H5, C6F5, p
      CF3C6H4, and 2,4,6-Me3C6H2) have been isolated and shown to exist in equilibra
      with the trinuclear complexes Ar2Zn3(OCHPr(i)2)4 and Ar2Zn when Ar = C6H5, C6F5,
      and p-CF3C6H4. The trinuclear complexes have also been prepared from reactions of
      the Ar2Zn compounds with the alcohol, which reveals that the ease of Zn-C(aryl)
      bond cleavage is sensitive to the nature of the Ar group: C6H5 > 4-CF3C6H4 >
      C6F5. The molecular structures of Ar2Zn3(OCHPr(i)2)4 where Ar = p-CF3C6H4 and
      C6F5 and [ArZn(OCHPr(i)2)]2 where Ar = C6F5, p-CF3C6H4, and 2,4,6-Me3C6H2 are
      reported based on single-crystal X-ray diffraction studies. The X-ray structure
      of Zn(p-CF3C6H4)2 is also reported. The reactivity of these new compounds toward
      the polymerization of propylene oxide (PO) and the copolymerization of PO and CO2
      have been investigated along with related reactions involving the partial
      hydrolysis of the Ar2Zn and R2Zn compounds, where R = t-Bu, n-Bu, and n-Oct.
      These results are compared with the previous studies employing Et2Zn as an
      organozinc precursor.

PMID- 15962987
TI  - Proton electroreduction catalyzed by cobaloximes: functional models for
      hydrogenases.
AB  - Cobaloximes have been examined as electrocatalysts for proton reduction in
      nonaqueous solvent in the presence of triethylammonium chloride.
      [Co(III)(dmgH)2pyCl], working at moderate potentials (-0.90 V/(Ag/AgCl/3 mol x L(
      1) NaCl) and in neutral conditions, is a promising catalyst as compared to other
      first-row transition metal complexes which generally function at more negative
      potentials and/or at lower pH. More than 100 turnovers can be achieved during
      controlled-potential electrolysis without detectable degradation of the catalyst.
      Cyclic voltammograms simulation is consistent with a heterolytic catalytic
      mechanism and allowed us to extract related kinetic parameters. Introduction of
      an electron-donating (electron-withdrawing) substituent in the axial pyridine
      ligand significantly increases (decreases) the rate constant of the catalytic
      cycle determining step. This effect linearly correlates with the Hammet
      coefficients of the introduced substituents. The influence of the equatorial
      glyoxime ligand was also investigated and the capability of the stabilized BF2
      bridged species [Co(dmgBF2)2(OH2)2] for electrocatalyzed hydrogen evolution
      confirmed.

PMID- 15962988
TI  - Aromatic interactions in unusual backbone nitrogen-coordinated zinc peptide
      complexes: a crystallographic and spectroscopic study.
AB  - A series of zinc complexes with dipeptide ligands of the type Dpg-Xaa was
      synthesized, where Dpg is dipicolylglycine and Xaa is phenylalanine (Phe),
      tyrosine (Tyr), tryptophan (Trp), 2-naphthylalanine (Nal), or glycine (Gly). It
      was shown that aromatic interactions promote the unusual coordination of an
      anionic peptide backbone nitrogen atom to zinc. This binding mode was, for the
      first time, characterized by X-ray structure analyses of the electrically neutral
      complexes [(Dpg-Phe)(-H)Zn], [(Dpg-Tyr)(-H)Zn], [(Dpg-Trp)(-H)Zn], and [(Dpg
      Nal)(-H)Zn]. The pKa values for amide nitrogen deprotonation were determined by
      1H NMR titrations {[(Dpg-Phe)Zn], 7.17; [(Dpg-Tyr)Zn], 6.85; [(Dpg-Trp)Zn], 6.85;
      [(Dpg-Nal)Zn], 6.64; [(Dpg-Gly)Zn], 8.54}. It was calculated that aromatic
      interactions contribute ca. -8 to -11 kJ/mol of stabilizing free enthalpy changes
      in the derivatives with aromatic amino acid side chains. These are the first
      quantitative data obtained for crystallographically characterized metal
      complexes. A comparison with the literature shows that it is difficult to
      distinguish between pi-cation attraction and pi-pi stacking. However, it is
      evident that modification of small peptides with synthetic pyridine ligands
      enhances their ability to stabilize secondary structures by noncovalent
      interactions. This is an important consideration for the design of biomimetic
      metallopeptides.

PMID- 15962989
TI  - Photoinduced electron transfer in platinum(II) terpyridinyl acetylide complexes
      connected to a porphyrin unit.
AB  - A series of six new dyads consisting of a zinc or magnesium porphyrin appended to
      a platinum terpyridine acetylide complex via a para-phenylene bisacetylene spacer
      are described. Different substituents on the 4' position of the terpyridinyl
      ligand were explored (OC7H15, PO3Et2, and H). The ground-state electronic
      properties of the dyads are studied by electronic absorption spectroscopy and
      electrochemistry, and they indicate some electronic interactions between the
      porphyrin subunit and the platinum complex. The photophysical properties of these
      dyads were investigated by steady-state, time-resolved, and femtosecond transient
      absorption spectroscopy in N,N-dimethylformamide solution. Excitation of the
      porphyrin unit leads to a very rapid electron transfer (2-20 ps) to the nearby
      platinum complex followed by an ultrafast charge recombination, thus preventing
      any observation of the charge separated state. The variation in the rate of the
      photoinduced electron transfer in the series of dyads is consistent with Marcus
      theory. The results underscore the potential of the para-phenylene bisacetylene
      bridge to mediate a rapid electron transfer over a long donor-acceptor distance.

PMID- 15962990
TI  - pH-specific aqueous synthetic chemistry in the binary cadmium(II)-citrate system.
      Gaining insight into cadmium(II)-citrate speciation with relevance to cadmium
      toxicity.
AB  - The involvement of Cd(II) in toxic manifestations and pathological aberrations in
      lower and higher organisms entails interactions with low and high molecular mass
      biological targets. To understand the relevant chemistry in aqueous media, we
      have launched pH-dependent synthetic efforts targeting Cd(II) with the
      physiological ligand citric acid. Reactions of Cd(II) with citric acid upon the
      addition of NaOH at pH 2.5 and pyridine at pH 3 and the addition of ammonia at pH
      approximately 7 led to the new complexes [Cd3(C6H5O7)2(H2O)5] x H2O (1) and
      (NH4)[Cd(C6H5O7)(H2O)] x H2O (2), respectively. Complexes 1 and 2 were
      characterized by elemental analysis, spectroscopy (FT-IR and NMR), and X-ray
      crystallography. Complex 1 crystallizes in the monoclinic space group P2(1)/n,
      with a = 18.035(6) A, b = 10.279(4) A, c = 12.565(4) A, beta = 109.02(1) degrees,
      V = 2202(2) A3, and Z = 4. Complex 2 crystallizes in the monoclinic space group
      P2(1), with a = 9.686(4) A, b = 8.484(4) A, c = 7.035(3) A, beta = 110.28(1)
      degrees, V = 542.3(4) A3, and Z = 2. Complex 1 is a trinuclear assembly with the
      citrate ligand securing a stable metallacyclic ring around one Cd(II), with the
      terminal carboxylates spanning into the coordination sphere of two nearby Cd(II)
      ions. Complex 2 contains mononuclear units of Cd(II) bound by citrate in an
      overall coordination number of 8. In both 1 and 2, the participating citrates
      exhibit three different modes of coordination, thus projecting a distinct yet
      variable aqueous structural chemistry of Cd(II) with physiological substrates.
      The pH-dependent chemistry and its apparent structural diversity validate past
      solution speciation studies, projecting the existence of mononuclear species such
      as the one in the anion of 2. The spectroscopic and structural properties of 2
      emphasize the significance of the information emerging from synthetic studies
      that otherwise would not have been revealed through conventional solution
      studies, while concurrently shedding light onto the linkage of the requisite
      chemistry with the potential biological toxicity of Cd(II).

PMID- 15962991
TI  - Theoretical designs for planar tetracoordinated carbon in Cu, Ag, and Au
      organometallic chemistry: a new target for synthesis.
AB  - In the past 30 years, substantial efforts and progress have been made in the
      design and synthesis of molecules containing tetracoordinated planar carbon, by
      overcoming the inherent preference for tetrahedral bonding. As a result, we have
      studied 12 organometallic molecules containing group 11 elements (i.e., M-X; M =
      Cu, Ag, and Au and X = I, II, III, and IV) using density functional theory to
      determine whether the central carbon atom exists in a planar geometry. Our
      theoretical findings suggest that in such M-X species, bonding interactions
      between the central carbon and the coinage metal ligands and between the metal
      ligands (i.e., metallophilic attractions) are both important in favoring planar
      tetracoordinated carbon compounds over the corresponding tetrahedral structures.
      The compounds studied in this work are seen as excellent targets for chemical
      synthesis.

PMID- 15962992
TI  - Reactions of methane with titanium atoms: CH3TiH, CH2=TiH2, agostic bonding, and
      (CH3)2TiH2.
AB  - Laser-ablated titanium atoms react with methane to form the insertion product
      CH3TiH, which undergoes a reversible photochemical alpha-H transfer to give the
      methylidene complex CH2=TiH2. On annealing a second methane activation occurs to
      produce (CH3)2TiH2. These molecules are identified from matrix infrared spectra
      by isotopic substitution (CH4, 13CH4, CD4, CH2D2) and comparison to DFT frequency
      calculations. The computed planar structure for singlet ground-state CH2=TiH2
      shows CH2 distortion and evidence for agostic bonding (H-C-Ti, 91.4 degrees),
      which is supported by the spectra for CHD=TiHD.

PMID- 15962993
TI  - Activation of metallocenes for olefin polymerization as monitored by IR
      spectroscopy.
AB  - Binary mixtures of Cp2ZrMe2, Cp2ZrCl2, dimethylaluminum chloride,
      trimethylaluminum, and methylaluminoxane (MAO), as well as Cp2ZrMe2 with boron
      based activators, have been studied by in situ IR spectroscopy (Cp =
      cyclopentadienyl, Me = methyl). The position of a strong band near 800 cm(-1),
      corresponding to the out-of-plane vibration of the Cp hydrogen atoms, is
      sensitive to the bonding environment around Zr and can be used to monitor
      reactions and the formation of new products in these mixtures. Harmonic
      frequencies determined by density functional theory correlate well with
      experimental values and have been used to assist in the interpretation of the
      data. The frequency of the Cp out-of-plane vibration, ranging from 797 to 832 cm(
      1) in our experiments, is found to increase with increasing electron density on
      the Cp ring and decreasing Zr-Cp distance. In the mixture of MAO and Cp2ZrMe2, a
      stable complex is rapidly formed at low Al/Zr ratios. A mechanism that may
      explain the need for a large MAO excess is proposed for the activation of
      metallocenes with MAO. The proposed mechanism involves the formation of dimers or
      oligomers of MAO cages that tend to dissipate the charge of the anion. This
      destabilization of the Cp2ZrMe2-MAO complex facilitates the formation of the
      catalytically active cation.

PMID- 15962994
TI  - Aqueous reductive dechlorination of chlorinated ethylenes with tetrakis(4
      carboxyphenyl)porphyrin cobalt.
AB  - The catalytic dechlorination of chlorinated ethylenes by 5,10,15,20-tetrakis(4
      carboxyphenyl)porphyrin cobalt ((TCPP)Co), a cobalt complex structurally similar
      to vitamin B12, was studied. It was found to have superior aqueous-phase
      dechlorination activity on chlorinated ethylenes (CEs) relative to vitamin B12.
      Bimolecular rate constants for the degradation of CEs by (TCPP)Co of 250, 24,
      0.24, and 1.5 M(-1) s(-1) were found for perchloroethylene (PCE),
      trichloroethylene (TCE), cis-dichloroethylene (cDCE), and trans-dichloroethylene
      (tDCE), respectively. Through kinetic analysis, the rate laws for PCE and TCE
      were determined to be first order in substrate and catalyst, and PCE degradation
      was shown to be sensitive to the concentration of the titanium citrate bulk
      reductant and pH. The importance of the Co(I) oxidation state on dehalogenation
      was studied with UV-vis absorbance spectroscopy, a variety of reducing agents,
      and cyclic voltammetry. Evidence of chlorovinyl complexes as potential catalytic
      cycle intermediates was obtained through the preparation of (TPP)Co(trans-C2H2Cl)
      and the observation of (TPP)Co(C2HCl2) and (TCPP)Co(C2HCl2) by mass spectrometry.
      The X-ray crystal structure of (TPP)Co(trans-C2H2Cl) is reported.

PMID- 15962995
TI  - Synthesis and structures of monomeric magnesium, calcium, strontium, and barium
      amides involving the N,N-(2,4,6-trimethylphenyl)(trimethylsilyl)amido ligand.
AB  - An extended family of aryl-substituted alkaline earth metal silylamides M{N(2,4,6
      Me3C6H2)(SiMe3)}donor(n) was prepared using alkane elimination (Mg), salt
      elimination (Ca, Sr, Ba), and direct metalation (Sr, Ba). Three different donors,
      THF, TMEDA (TMEDA = N,N,N',N'-tetramethylethylenediamine), and PMDTA (PMDTA =
      N,N,N',N'',N''-pentamethyldiethylenetriamine) were employed to study their
      influence on the coordination chemistry of the target compounds, producing
      monomeric species with the composition M{N(2,4,6-Me3C6H2)(SiMe3)}2(THF)2 (M = Mg,
      Ca, Sr, Ba), M{N(2,4,6-Me3C6H2)(SiMe3)}2TMEDA (M = Ca, Ba), and M{N(2,4,6
      Me3C6H2)(SiMe3)}2PMDTA (M = Sr, Ba). For the heavier metal analogues, varying
      degrees of agostic interactions are completing the coordination sphere of the
      metals. Compounds were characterized using IR and NMR spectroscopy in addition to
      X-ray crystallography.

PMID- 15962996
TI  - Preparation and crystal structures of a series of titanium(III) 9-BBN hydroborate
      complexes containing Ti...H agostic interactions.
AB  - 9-BBN hydroborate complexes Ti{(mu-H)2BC8H14}3(THF)2 (1), Ti{(mu
      H)2BC8H14}3(OEt2) (2), and [K(OEt2)4]-[Ti{(mu-H)2BC8H14}4] (4) were formed from
      the reaction of TiCl4 with K[H2BC8H14] in diethyl ether or THF. Ti{(mu
      H)2BC8H14}3(PhNH2) (3) was isolated from the reaction of 2 with aniline in
      diethyl ether. In the formation of these complexes, Ti(IV) is reduced to Ti(III).
      The coordinated diethyl ether in 2 can be displaced by the stronger bases THF and
      aniline, to form 1 and 3, respectively. All of the compounds were characterized
      by single-crystal X-ray diffraction analysis. In complex 1, which contains two
      coordinated THF ligands, the titanium possesses a 17 electron configuration and
      there is no evidence for agostic interaction. Complexes 2 and 3 contain only one
      coordinated ether or aniline ligand, and the titanium possesses a 15 electron
      configuration. In these compounds, a C-H hydrogen on an alpha carbon on the
      BC8H14 unit of a 9-BBN hydroborate ligand forms an agostic interaction with the
      titanium. Criteria for assessing the existence of agostic interactions are
      discussed. As the potassium salt, the anion of complex 4 is more stable than the
      complexes 1-3. Organometallic anions of the type [ML4]- for titanium(III) are
      rare.

PMID- 15962997
TI  - Synthesis, X-ray diffraction studies, and DFT calculations on hexacoordinated
      germanium derivatives: the case of germaspirobis(ocanes).
AB  - Synthesis of the title compounds, viz. [RN(CH2CHR'O)2]2Ge (1, R = Me, R' = H; 2,
      R = Me, R' = Ph; 3, R = Ph, R' = H), by the reaction of 2 equiv of corresponding
      dialkanolamines RN(CH2CHR'OH)2 (4, R = Me, R' = H; 5, R = Me, R' = Ph; 6, R = Ph,
      R' = H) with (AlkO)4Ge is reported. Composition and structures of all novel
      compounds were established by 1H and 13C NMR spectroscopy and mass spectrometry
      as well as elemental analysis data. The single-crystal X-ray diffraction of 2 has
      clearly indicated the presence of two transannular interactions Ge<--N in the
      compound. N atoms are cis-orientated. The compound 3 possesses long Ge...N
      distances. The structural data obtained from geometry optimizations by DFT
      calculations on 1-3 reproduces experimental results. Both cis- and trans-isomers
      were studied, and cis-configuration was found to be more thermodynamically stable
      for all three compounds. The transition states for possible cis <--> trans
      rearrangement processes in 1-3 were calculated. The properties of the Ge-O and
      Ge<--N bonds in 1-3 were analyzed by the AIM approach. The interactions between
      the Ge atom and N atoms as well as O atoms possess predominantly ionic character.

PMID- 15962998
TI  - Migraine during pregnancy: options for therapy.
AB  - Migraine is common during pregnancy, but fortunately this combination of
      conditions obviously exists for only a finite period. The greatest frequency of
      migraine attacks occurs during the first trimester. Accurate diagnosis is a sine
      qua non in this setting as in any headache patient. It is in the first trimester
      that the fetus is at greatest risk from abortifacient and teratogenic drugs, and
      when very early pregnancy may be undiagnosed. Ergot alkaloids (including
      methysergide) should be avoided during pregnancy because of their teratogenicity,
      and most other drug classes should be used only when unavoidable. The use of
      prophylactic agents during pregnancy should be the exception, not the rule, and
      preferably only during the second and third trimesters; propranolol is probably
      safest in this situation. De novo headache during pregnancy usually requires
      expert review of the patient. Treatment tactics for uncomplicated migraine in
      pregnancy depend on the concurrent clinical situation. Paracetamol
      (acetaminophen) is the mainstay for the patient whose typical attacks continue
      into the first trimester. If paracetamol is insufficient, then partial agonist
      opioids may be used if typical migraine attacks persist in the second and third
      trimesters (which is uncommon). 'Chronic migraine' in pregnancy, i.e. >or=15
      headache days per month, is rare, and is the greatest therapeutic challenge. Co
      morbidities such as depression or epilepsy require specialised approaches. The
      complexities associated with these tactics are discussed in this article, and it
      is emphasised that none has the specific approval of regulatory authorities.
      Heightened pharmacovigilance will better inform the future pregnant migraineur.
      However, this type of information is less likely to be available for novel
      classes of neuropharmacological agents than for existing ones.

PMID- 15962999
TI  - Medication overuse headache in patients with primary headache disorders:
      epidemiology, management and pathogenesis.
AB  - Medication overuse headache (MOH) is a common medical condition that is
      associated with considerable long-term morbidity and disability. Patients
      experiencing MOH have primary headache disorders (migraine, tension-type headache
      [TTH] or the combination of migraine and TTH) that change to a pattern of daily
      or near-daily headaches over a period of years or decades following the overuse
      of symptomatic headache medications. Overused drugs include analgesics, ergot
      alkaloids, serotonin 5-HT(1B/1D) receptor agonists ('triptans') and medications
      containing barbiturates, codeine, caffeine, tranquillisers and mixed analgesics.
      Affected patients usually have a long history of primary headache, overuse of
      medications and MOH before they consult a physician for care. Patients with MOH
      are usually managed in specialist centres by withdrawal of the overused drugs and
      treatment of withdrawal symptoms (on an inpatient or outpatient basis), headache
      prophylaxis and limited use of symptomatic acute medications. Most patients
      respond to this therapy, although the prognosis is not always good and >or=50%
      may lapse over an initial 5-year follow-up period. The best practical strategy at
      present is to prevent the overuse of drugs in the first place by patient
      education and formal management approaches conducted in primary care to treat the
      primary headache before it changes to MOH. The quality of the clinical evidence
      on MOH is suboptimal and further biological and clinical research is urgently
      required to help facilitate the management of these patients more effectively in
      the future.

PMID- 15963000
TI  - Efficacy of olanzapine and ziprasidone for the treatment of schizophrenia: a
      systematic review.
AB  - It is difficult to determine the relative efficacy of atypical antipsychotics for
      the treatment of schizophrenia, based on the available literature. The purpose of
      this article is to review and compare the efficacy of two atypical
      antipsychotics: olanzapine and ziprasidone.This review focused on randomised
      trials in which these two antipsychotics were compared with placebo, conventional
      antipsychotics and each other. Common efficacy measures were the Brief
      Psychiatric Rating Scale, Positive and Negative Syndrome Scale and Schedule for
      Assessment of Negative Symptoms. When sufficient data were available, the mean
      treatment effect (with 95% confidence intervals) was computed and presented.
      Olanzapine was consistently found to be significantly superior to placebo and
      comparable with, or superior to, haloperidol for the treatment of overall,
      positive and negative schizophrenic symptoms. Ziprasidone appears to have
      significantly greater efficacy than placebo for overall and negative symptoms,
      but it remains uncertain whether ziprasidone is comparable in efficacy with
      conventional antipsychotics such as haloperidol. Two unpublished clinical trials
      have directly compared olanzapine and ziprasidone. One of these trials found no
      significant efficacy differences between the two drugs, whereas the results of
      the other study favoured olanzapine. Compared with ziprasidone, olanzapine has a
      larger body of evidence supporting its efficacy, and a greater proportion of
      findings for olanzapine have been published, allowing for greater scrutiny of
      results. Both drugs appear to be superior to placebo for the treatment of overall
      and negative symptoms of schizophrenia, but olanzapine generally compares more
      favourably with conventional antipsychotics. Firm conclusions regarding the
      comparison between olanzapine and ziprasidone require additional published trials
      on ziprasidone, particularly in direct comparison with olanzapine.

PMID- 15963003
TI  - Spotlight on olanzapine in bipolar I disorder.
AB  - Olanzapine is an atypical antipsychotic that is approved in the US and Europe for
      the oral treatment of acute manic episodes in patients with bipolar I disorder
      and for maintenance therapy to prevent recurrence in responders. Oral olanzapine
      is effective in the treatment of bipolar mania, both as single agent therapy and
      as adjunctive therapy in combination with lithium or valproate semisodium. In the
      treatment of acute episodes, olanzapine is superior to placebo and at least as
      effective as lithium, valproate semisodium, haloperidol and risperidone in
      reducing the symptoms of mania and inducing remission. Additional comparative
      studies are required to determine the efficacy of olanzapine relative to newer
      atypical antipsychotics such as quetiapine, ziprasidone and aripiprazole.
      Olanzapine is also effective at delaying or preventing relapse during long-term
      maintenance therapy in treatment responders and is currently the only atypical
      antipsychotic approved for this indication. Current evidence suggests that
      olanzapine may be more effective than lithium in preventing relapse into mania,
      but not relapse into depression or relapse overall. Olanzapine is generally well
      tolerated and, although it is associated with a higher incidence of weight gain
      than most atypical agents, it has a low incidence of extrapyramidal symptoms.
      Therefore, oral olanzapine is a useful first-line or adjunctive agent for both
      the acute treatment of manic episodes and the long-term prevention of relapse
      into manic, depressive or mixed episodes associated with bipolar I disorder.

PMID- 15963002
TI  - Thrombolysis in acute ischaemic stroke: a guide to patient selection.
AB  - Thrombolysis should be a routine treatment for selected patients with acute
      ischaemic stroke and shows promise in a much larger group of patients. This
      recommendation is based on data from two completed meta-analyses: the Cochrane
      Library and the rt-PA Study Group individual patient meta-analysis. In patients
      with ischaemic stroke, treatment with alteplase (recombinant tissue plasminogen
      activator; rt-PA) is associated with a non-significant excess of deaths,
      equivalent to about 19 extra deaths per 1000 treated. Furthermore, thrombolysis,
      regardless of which drug is used, definitely increases the odds of fatal
      intracranial haemorrhage by 4-fold. However, despite these risks, thrombolysis
      with alteplase reduces the odds of death or disability, with the benefit being
      equivalent to about 55 extra independent survivors per 1000 treated.
      Unfortunately, there are currently too few data to provide a comprehensive guide
      to patient selection. The available data suggest that younger patients (<80 years
      of age) who can be treated with alteplase within 3 hours of stroke onset have the
      most to gain, equivalent to about 100 more independent survivors per 1000
      treated. The role of thrombolysis beyond 3 hours, in those with more extensive CT
      scan ischaemic change, and patients >80 years of age needs further evaluation. In
      summary, thrombolysis with alteplase is now an established treatment for acute
      ischaemic stroke, but clinicians need to cooperate in terms of enrolling more
      patients in further trials if we are to get the most out of this important
      treatment.

PMID- 15963001
TI  - Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the
      mechanism of action.
AB  - Acamprosate is an abstinence-promoting drug widely used in the treatment of
      alcohol dependence but which has a mechanism of action that has remained obscure
      for many years. Recently, evidence has emerged that this drug may interact with
      excitatory glutamatergic neurotransmission in general and as an antagonist of the
      metabotropic glutamate receptor subtype 5 (mGluR5) in particular. These findings
      provide, for the first time, a satisfactory, unifying hypothesis that can bring
      together and explain the diverse neurochemical effects of acamprosate. Glutamic
      acid is involved in several aspects of alcohol dependence and withdrawal, many of
      which can be modified by acamprosate. For example, during chronic exposure to
      alcohol, the glutamatergic system becomes upregulated, leaving the brain exposed
      to excessive glutamatergic activity when alcohol is abruptly withdrawn. The surge
      in glutamic acid release that occurs following alcohol withdrawal can be
      attenuated by acamprosate. The elevated extracellular levels of glutamic acid
      observed in withdrawal, together with supersensitivity of NMDA receptors, may
      expose vulnerable neurons to excitotoxicity, possibly contributing to the
      neuronal loss sometimes observed in chronic alcohol dependence. In vitro studies
      suggest that the excitotoxicity produced by ethanol can effectively be blocked by
      acamprosate. Moreover, glutamatergic neurotransmission plays an important role in
      the acquisition of cue-elicited drinking behaviours, which again can be modulated
      by acamprosate. In conclusion, the glutamatergic hypothesis of the mechanism of
      action of acamprosate helps explain many of its effects in human alcohol
      dependence and points the way to potential new activities, such as
      neuroprotection, that merit exploration in the clinic.

PMID- 15963004
TI  - Reporting of deaths during pre-approval clinical trials for advanced HIV-infected
      populations.
AB  - The Division of Antiviral Drug Products of the US FDA has regulatory authority
      over the investigational new drugs under development by various sponsors to treat
      HIV-infected populations. The FDA and the sponsors of investigational new drugs
      use the Code of Federal Regulations to guide the entire drug development process,
      in order to ensure that safe and efficacious drugs are brought to market. To
      achieve this goal, diligent monitoring for safety during the pre-approval phase
      of new drug development is particularly crucial. When deciding what adverse
      experiences on clinical trials should be expeditiously reported, the Division
      recommends a conservative interpretation of the Code of Federal Regulations,
      where an adverse experience in a clinical trial of advanced HIV-infected patients
      is considered to be 'associated with the use of the drug' when the relationship
      cannot be ruled out with objective evidence. Fatal adverse experiences for
      subjects on clinical trials should be especially scrutinised. Safety reporting
      should be expedited when death occurs during clinical trials of advanced HIV
      infected populations. The three components of an expedited reportable death
      occurrence, namely 'serious', 'unexpected' and 'associated with the drug use' as
      they relate to advanced HIV-infected populations, are discussed in this article.
      An occurrence of death is by definition serious. Unexpected experiences are
      unlisted adverse experiences, but need to be put into the context of specificity
      and severity. 'Associated with the drug use' has been clarified as 'relationship
      to the drug cannot be ruled out'. Because death in the advanced HIV-infected/AIDS
      population is usually a complex event, the possible contribution of the study
      drug is difficult to rule out. Thus, if the three components of the reporting
      requirement are met or insufficient information is available to make a firm
      determination of causality by the seventh day of the reporting period, the
      Division of Antiviral Drug Products expects expedited death reports on subjects
      participating in investigational new drug clinical studies.

PMID- 15963005
TI  - Treatment with selective serotonin reuptake inhibitors in the third trimester of
      pregnancy: effects on the infant.
AB  - Pharmacotherapy in pregnant women is often necessary to treat chronic or
      relapsing depression or anxiety disorders. Studies that have evaluated the safety
      of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have not
      shown an enhanced risk of major congenital malformations and these results may
      have contributed to the increasing use of these agents during pregnancy. Fewer
      studies have assessed the safety of SSRIs in the third trimester of pregnancy.
      This article reviews available human data on the safety of SSRI treatment in the
      third trimester. The main purpose is to present and discuss the existing
      literature on the risks to the infant and to suggest treatment guidelines for the
      use of SSRIs in late pregnancy. The use of SSRIs in the third trimester has shown
      various perinatal complications, most frequently respiratory distress,
      irritability and feeding problems. Further studies are needed to evaluate the
      frequency of these complications and to elucidate whether the symptoms represent
      a direct serotonergic effect or are a drug withdrawal effect. Studies have shown
      conflicting results with respect to whether SSRI exposure decreases birthweight
      and increases the risk of premature delivery. A few case reports have described
      intracerebral haemorrhage in neonates after maternal SSRI treatment, but it is
      not known whether the frequency of such complications is higher than in unexposed
      neonates. Data on possible long-term effects of prenatal SSRI exposure on
      psychomotor and behavioural development are very sparse. Our interpretation of
      the current literature suggests that the risk of not receiving adequate
      antidepressant treatment in the third trimester when indicated outweighs the
      risks of adverse events in the infant. Thus, adequate pharmacological treatment
      should not be withheld from a depressed pregnant woman in late pregnancy.
      However, the neonate should be monitored for possible adverse effects after
      maternal use of an SSRI in the third trimester.

PMID- 15963007
TI  - Drug interactions of clinical importance with antihyperglycaemic agents: an
      update.
AB  - Because management of type 2 diabetes mellitus usually involves combined
      pharmacological therapy to obtain adequate glucose control and treatment of
      concurrent pathologies (especially dyslipidaemia and arterial hypertension), drug
      drug interactions must be carefully considered with antihyperglycaemic drugs.
      Additive glucose-lowering effects have been extensively reported when combining
      sulphonylureas (or the new insulin secretagogues, meglitinide derivatives, i.e.
      nateglinide and repaglinide) with metformin, sulphonylureas (or meglitinide
      derivatives) with thiazolidinediones (also called glitazones) and the biguanide
      compound metformin with thiazolidinediones. Interest in combining alpha
      glucosidase inhibitors with either sulphonylureas (or meglitinide derivatives),
      metformin or thiazolidinediones has also been demonstrated. These combinations
      result in lower glycosylated haemoglobin (HbA(1c)), fasting glucose and
      postprandial glucose levels than with either monotherapy. Even if modest
      pharmacokinetic interferences have been reported with some combinations, they do
      not appear to have important clinical consequences. No significant adverse
      effects, except a higher risk of hypoglycaemic episodes that may be attributed to
      better glycaemic control, occur with any combination. Challenging the classical
      dual therapy with sulphonylurea plus metformin, there is a recent trend to use
      alternative dual combinations (sulphonylurea plus thiazolidinedione or metformin
      plus thiazolidinedione). In addition, triple therapy with the addition of a
      thiazolidinedione to the metformin-sulphonylurea combination has been recently
      evaluated and allows glucose targets to be reached before insulin therapy is
      considered. This triple therapy appears to be safe, with no deleterious drug-drug
      interactions being reported so far.Potential interferences may also occur between
      glucose-lowering agents and other drugs, and such drug-drug interactions may have
      important clinical implications. Relevant pharmacological agents are those that
      are widely coadministered in diabetic patients (e.g. lipid-lowering agents,
      antihypertensive agents); those that have a narrow efficacy/toxicity ratio (e.g.
      digoxin, warfarin); or those that are known to induce (rifampicin [rifampin]) or
      inhibit (fluconazole) the cytochrome P450 (CYP) system. Metformin is currently a
      key compound in the pharmacological management of type 2 diabetes, used either
      alone or in combination with other antihyperglycaemics. There are no clinically
      relevant metabolic interactions with metformin, because this compound is not
      metabolised and does not inhibit the metabolism of other drugs. In contrast,
      sulphonylureas, meglitinide derivatives and thiazolidinediones are extensively
      metabolised in the liver via the CYP system and thus, may be subject to drug-drug
      metabolic interactions. Many HMG-CoA reductase inhibitors (statins) are also
      metabolised via the CYP system. Even if modest pharmacokinetic interactions may
      occur, it is not clear whether drug-drug interactions between oral
      antihyperglycaemic agents and statins may have clinical consequences regarding
      both efficacy and safety. In contrast, a marked pharmacokinetic interference has
      been reported between gemfibrozil and repaglinide and, to a lesser extent,
      between gemfibrozil and rosiglitazone. This leads to a drastic increase in plasma
      concentrations of each antihyperglycaemic agent when they are coadministered with
      the fibric acid derivative, and an increased risk of adverse effects. Some
      antihypertensive agents may favour hypoglycaemic episodes when co-prescribed with
      sulphonylureas or meglitinide derivatives, especially ACE inhibitors, but this
      effect seems to result from a pharmacodynamic drug-drug interaction rather than
      from a pharmacokinetic drug-drug interaction. No, or only modest, interferences
      have been described with glucose-lowering agents and other pharmacological
      compounds such as digoxin or warfarin. The effects of inducers or inhibitors of
      CYP isoenzymes on the metabolism and pharmacokinetics of the glucose-lowering
      agents of each pharmacological class has been tested. Significantly increased
      (with CYP inhibitors) or decreased (with CYP inducers) plasma levels of
      sulphonylureas, meglitinide derivatives and thiazolidinediones have been reported
      in healthy volunteers, and these pharmacokinetic changes may lead to enhanced or
      reduced glucose-lowering action, and thus hypoglycaemia or worsening of metabolic
      control, respectively. In addition, some case reports have evidenced potential
      drug-drug interactions with various antihyperglycaemic agents that are usually
      associated with a higher risk of hypoglycaemia.

PMID- 15963006
TI  - Improving the tolerability of anticholinergic agents in the treatment of
      overactive bladder.
AB  - Pharmacological treatment for overactive bladder has centred around the
      interruption of the detrusor activity that is central to urge and incontinence
      symptoms. The majority of patients with this disorder are treated with
      antimuscarinic agents. These drugs have been demonstrated to improve urgency,
      frequency of micturition and urge incontinence, all of which are primary symptoms
      of overactive bladder; however, they are also commonly associated with
      anticholinergic adverse effects, most notably dry mouth. Attempts to increase
      tolerability have included the development of advanced formulations that regulate
      release of the active ingredient and the development of pharmacological agents
      that target the desired bladder receptors more specifically and accurately.
      Although all agents provide good efficacy, tolerability is greatly affected by
      the formulation used to deliver the active pharmacological agent, as well as the
      specificity of the targeted receptors. Clinical trials involving a transdermal
      formulation of oxybutynin have shown that this delivery method may be associated
      with a lower incidence of anticholinergic adverse events compared with both the
      immediate-release and the extended-release oral formulations of traditional
      agents, as well as the most recently approved agents - trospium chloride,
      solifenacin and darifenacin. Much is still being learned about the function and
      specificity of muscarinic receptors, which will support the development of agents
      with sustained efficacy and enhanced tolerability compared with the available
      formulations to date. These include the S-isomer of oxybutynin, as well as
      selective muscarinic M2 receptor antagonists.

PMID- 15963009
TI  - From the Uppsala monitoring centre: a review of viewpoint part 1 and part 2.
AB  - The core task of the Uppsala Monitoring Centre (UMC) is the collection and
      processing of adverse drug reaction reports from member countries of the WHO
      Programme for International Drug Monitoring to detect early signals of potential
      drug hazards. Also a high priority is the communication of information about drug
      safety issues to the widest possible professional and general audiences in order
      to improve patient safety and welfare. The publication of the two parts of the
      publication Viewpoint represents a pioneering effort to provide easily accessible
      information on international pharmacovigilance for lay and specialist readers.

PMID- 15963008
TI  - Corticosteroid-associated tendinopathies: an analysis of the published literature
      and spontaneous pharmacovigilance data.
AB  - INTRODUCTION AND OBJECTIVE: Corticosteroids may cause tendinopathies, an adverse
      effect that is not well known and characterised, although it was initially
      described more than 40 years ago. This study was conducted in order to
      characterise the important aspects of this adverse reaction, such as the role
      played by routes of corticosteroid administration, therapy duration,
      comedication, cumulative corticosteroid dose and underlying disease. STUDY DESIGN
      AND METHODS: Published case reports of tendinopathies that were associated with
      corticosteroid use were identified by a comprehensive literature search using the
      databases MEDLINE, Pharm-line, EMBASE, ToxFile, Adis Inpharma, International
      Pharmaceutical Abstracts, Drug Information Fulltext and PASCAL. The reference
      lists of all pertinent articles were cross-referenced to retrieve additional
      cases. Spontaneous reports were requested from the Uppsala Monitoring Centre (the
      WHO Collaborating Centre for International Drug Monitoring). Information of
      published and spontaneous reports was analysed with regard to age, sex,
      underlying disease, individual corticosteroids, equivalent corticosteroid dose,
      latency time, cumulative dose, route of administration, comedication and type of
      tendinopathy. RESULTS: We included and analysed 73 published case reports and
      case series involving 133 patients and 191 spontaneous reports of corticosteroid
      associated tendinopathies. The proportion of women with tendinopathies was 50.8%
      and 41.0%, respectively. The mean age (+/- standard deviation) of patients with a
      tendinopathy was 50 +/- 17 years and 61 +/- 16 years, respectively. The
      predominant routes of administration were oral (33% of published cases and 47% of
      spontaneous cases) and intra-articular (35% of the published cases or parenteral
      (7% of the spontaneous cases). There were isolated cases of tendinopathy after
      inhaled or topical (i.e. ocular, cutaneous, nasal) corticosteroid use.
      Tendinopathies that were reported in the literature cases consisted mainly of
      tendon ruptures (93%), predominantly of the Achilles tendon. Of the spontaneous
      cases, 31% had a rupture and the remaining cases had a tendinitis or an
      unspecified tendon disorder. CONCLUSION: Oral and parenteral applications,
      especially intra-articular use, were the most prevalent routes of administration
      in cases with corticosteroid-associated tendinopathies. However, topical
      application has also been rarely associated with tendinopathies. Future
      pharmacoepidemiological studies should further address this issue to quantify the
      risk of corticosteroid-associated tendinopathies.

PMID- 15963010
TI  - The pharmacovigilance system in India.

PMID- 15963011
TI  - Renal adverse effects of interferon-alpha.

PMID- 15963012
TI  - The easiest cut: managing elective surgery in the public sector.
AB  - The problem of surgical waiting lists requires multifactorial solutions.

PMID- 15963014
TI  - Tailoring access to high cost, genetically targeted drugs.
AB  - Assessment of real cost effectiveness, with data linked to individual health
      outcomes while protecting patient privacy, is an essential challenge we need to
      meet.

PMID- 15963013
TI  - Clinicians prescribing exercise: is air pollution a hazard?
AB  - A common-sense approach to reducing exposure to polluted air is required.

PMID- 15963015
TI  - Is this clinical trial fully registered? A statement from the International
      Committee of Medical Journal Editors.

PMID- 15963016
TI  - Cancellation of operations on the day of intended surgery at a major Australian
      referral hospital.
AB  - OBJECTIVE: To establish the rate of and reasons for cancellations of surgery on
      the scheduled day in an Australian hospital. DESIGN: Prospective survey. SETTING:
      Major metropolitan tertiary hospital, 13 May to 15 November 2002. MAIN OUTCOME
      MEASURES: Proportion of operations cancelled on the day of surgery, obtained each
      day from the operating theatre list and a separate list of additions and
      cancellations compiled on the day; reasons for cancellations from the
      cancellation list, extended or confirmed, as necessary, by questioning of
      bookings and ward staff, or members of the surgical team; estimated and actual
      duration of each operation and patient information from hospital clinical
      records. RESULTS: 7913 theatre sessions were scheduled by 133 surgeons in the
      study period; 941 of these (11.9%) were cancelled on the day, including 724 of
      5472 (13.2%) elective procedures on working weekdays. Main reasons for
      cancellation were: no theatre time due to over-run of previous surgery (18.7%);
      no postoperative bed (18.1%); cancelled by patient (17.5%); and change in patient
      clinical status (17.1%). Procedural reasons (including patient not ready, no
      surgeon, list error, administrative cause, and communication failure) totalled
      21.0%. Ear, nose and throat surgery experienced the most cancellations (19.6%),
      followed by cardiothoracic surgery (15.8%). CONCLUSIONS: There were five major
      reasons of similar magnitude for on-the-day surgery cancellations. We estimated
      that 60% of cancellations of elective procedures were potentially avoidable.
      Change of one factor leading to cancellation (eg, provision of more postoperative
      beds) is not likely to lead to improvement unless the other major factors are
      also tackled.

PMID- 15963017
TI  - A community-based intervention to reduce antibiotic use for upper respiratory
      tract infections in regional South Australia.
AB  - OBJECTIVE: To evaluate the effectiveness of a community-based and GP-based
      intervention in reducing unnecessary antibiotic prescribing for upper respiratory
      tract infections (URTIs) including sore throats, sinusitis and otitis media.
      DESIGN: Analysis of pharmacy dispensing data in June to October before (2000) and
      after (2001) the intervention, which commenced on 25 June 2001. SETTING AND
      PARTICIPANTS: Local consumers, health professionals, the Adelaide Southern
      Division of General Practice, the South Australian Government, and the local
      media in a rural region of South Australia, covering about 2000 square
      kilometres, with a population of over 20 000. INTERVENTION: Community
      dissemination of consumer information on antibiotic use for URTIs (including a
      local media campaign) and education of health professionals (including sessions
      with general practitioners at the four practices in the study area) on current
      Australian therapeutic guidelines for antibiotics, and a validated clinical
      scoring system for decision making in managing sore throat. MAIN OUTCOME
      MEASURES: Total dispensing data from local pharmacies for the months of June to
      October in 2000 and 2001, covering the six antibiotics considered most likely to
      be used for URTIs (amoxycillin, amoxycillin/clavulanic acid, cefaclor,
      doxycycline, erythromycin and roxithromycin). RESULTS: The dispensing of the six
      antibiotics reduced by 32% overall, from 77.1 to 52.9 defined daily doses per
      1000 population per day, with statistically significant reductions in the range
      of 31%-70% for individual antibiotics; there was no reduction for amoxycillin
      with or without clavulanic acid. CONCLUSION: The intervention was associated with
      reduced dispensing of unnecessary antibiotics for URTIs.

PMID- 15963018
TI  - Adult domiciliary oxygen therapy. Position statement of the Thoracic Society of
      Australia and New Zealand.
AB  - Patients with chronic obstructive pulmonary disease and a stable daytime PaO2 of
      < or = 55 mmHg (7.3 kPa) live longer and have a better quality of life if
      provided with long-term continuous oxygen therapy. It is reasonable to offer
      continuous oxygen therapy also to patients with other lung diseases that cause
      chronic hypoxaemia. Indications for supplemental oxygen therapy during exercise
      (ambulatory oxygen therapy) and sleep (nocturnal oxygen therapy) are less clear.

PMID- 15963019
TI  - Effectiveness of treatments for depression in older people.
AB  - OBJECTIVE: To conduct a systematic review of the evidence for the effectiveness
      of a range of possible treatments for depression in older people. DATA SOURCES:
      Literature search using the PubMed, PsycInfo and Cochrane Library databases. DATA
      SYNTHESIS: Treatments that have been suggested to be effective for depression
      were grouped under three categories: medical treatments, psychological
      treatments, and lifestyle changes/alternative treatments. We describe each
      treatment, review the studies of its effectiveness in people aged > or = 60
      years, and give a rating of the level of evidence. CONCLUSIONS: The treatments
      with the best evidence of effectiveness are antidepressants, electroconvulsive
      therapy, cognitive behaviour therapy, psychodynamic psychotherapy, reminiscence
      therapy, problem-solving therapy, bibliotherapy (for mild to moderate depression)
      and exercise. There is limited evidence to support the effectiveness of
      transcranial magnetic stimulation, dialectical behaviour therapy, interpersonal
      therapy, light therapy (for people in nursing homes or hospitals), St John's wort
      and folate in reducing depressive symptoms.

PMID- 15963020
TI  - Sight-seeing in the Solomon Islands.

PMID- 15963021
TI  - Severe renal failure and nephrocalcinosis in anorexia nervosa.
AB  - Two patients with anorexia nervosa and raised serum creatinine levels were found
      to have nephrocalcinosis on renal biopsy, an association not previously
      described.

PMID- 15963022
TI  - Potential pitfalls in the diagnosis of phaeochromocytoma.
AB  - Six patients being evaluated for phaeochromocytoma had misleading investigative
      findings: all initially had raised urinary catecholamine levels, and five had
      adrenal masses on imaging studies. Adrenalectomy in these five patients revealed
      only one pathologically confirmed phaeochromocytoma. Tricyclic antidepressant use
      produced misleading elevations in urinary catecholamine levels in three patients.
      24-hour urine studies should be performed at least twice, after eliminating
      confounding factors (stressors, medications).

PMID- 15963023
TI  - 11. Fractures and minor head injuries: minor injuries in children II.
AB  - Fractures in children are common, but the plasticity of children's bones means
      that they may be incomplete. If a child has deformity, swelling or bony point
      tenderness in a limb after a fall, it is likely to be fractured. A fractured limb
      that appears deformed will most probably need to be reduced. Effective splinting,
      using whatever means is readily available, and early, adequate analgesia, can
      ameliorate the severe pain associated with a fracture. In young children with
      open growth plates, Salter-Harris type I injuries of the distal fibula are more
      common than ligament injuries of the ankle. After an ankle ligament injury,
      functional treatment--brace or tapes, with active physiotherapy--results in a
      better outcome than immobilisation. A child with a head injury, who does not lose
      consciousness, has only one or no episodes of vomiting, and is stable, alert and
      interactive, and neurologically normal, is extremely unlikely to have sustained
      an intracranial injury.

PMID- 15963024
TI  - Should thyroxine tablets be refrigerated? Have we got it wrong in Australia?

PMID- 15963025
TI  - Staphylococcal toxic shock syndrome: still a problem.

PMID- 15963026
TI  - Weight gain and diabetes with "second-generation" antipsychotic drugs.

PMID- 15963027
TI  - A syndromic rash in patients attending methadone clinics in New South Wales.

PMID- 15963028
TI  - Life-threatening milk-alkali syndrome resulting from antacid ingestion during
      pregnancy.

PMID- 15963030
TI  - The GTPase RhoA increases utrophin expression and stability, as well as its
      localization at the plasma membrane.
AB  - The Rho family of small GTPases are signalling molecules involved in cytoskeleton
      remodelling and gene transcription. Their activities are important for many
      cellular processes, including myogenesis. In particular, RhoA positively
      regulates skeletal-muscle differentiation. We report in the present study that
      the active form of RhoA increases the expression of utrophin, the autosomal
      homologue of dystrophin in the mouse C2C12 and rat L8 myoblastic cell lines. Even
      though this RhoA-dependent utrophin increase is higher in proliferating
      myoblasts, it is maintained during myogenic differentiation. This occurs via two
      mechanisms: (i) transcriptional activation of the utrophin promoter A and (ii)
      post-translational stabilization of utrophin. In addition, RhoA increases plasma
      membrane localization of utrophin. Thus RhoA activation up-regulates utrophin
      levels and enhances its localization at the plasma membrane.

PMID- 15963031
TI  - Diabetic ketoacidosis in children: the problems continue.

PMID- 15963032
TI  - Predictors of glucose control in children and adolescents with type 1 diabetes
      mellitus.
AB  - AIMS: To evaluate the glucose control [(as measured by hemoglobin A1c (HbA1c)],
      the factors associated with glycemic control, and possible explanations for these
      associations in a sample of children and adolescents with type 1 diabetes.
      METHODS: Data were collected on 155 children and adolescents, with type 1
      diabetes mellitus, attending a multidisciplinary diabetes clinic in Portland, OR.
      Patients' hospital charts were reviewed to determine demographic factors, disease
      related characteristics, and HbA1c level. RESULTS: Mean percent HbA1c was 9.3.
      Adolescents between the ages of 14 and 18 yr were in poorer metabolic control
      (adjusted mean percent HbA1c 0.56 higher than children 2-8 yr). Children who
      attended the clinic three to four times in the previous year were in better
      control (adjusted mean percent HbA1c 0.46 lower than those who visited two or
      fewer times and 1.11 lower than those who attended five or more times). Children
      with married parents were in better glycemic control than those of single,
      separated, or divorced parents (adjusted mean percent HbA1c 0.47 lower for
      children of married parents). This effect appeared to be mediated, in part, by
      the number of glucose checks performed per day. CONCLUSIONS: This study suggests
      that adolescents should be targeted for improved metabolic control. Diabetes team
      members need to be aware of changing family situations and provide extra support
      during stressful times. Regular clinic attendance is an important component of
      intensive diabetes management. Strategies must be developed to improve
      accessibility to the clinic and to identify patients who frequently miss
      appointments.

PMID- 15963033
TI  - Clinical presentation of type 1 diabetes.
AB  - OBJECTIVE: To identify the presenting features of type 1 diabetes in a national
      incident cohort aged under 15 yr, the duration of symptoms, the occurrence of
      diabetic ketoacidosis (DKA) at presentation, and the frequency of a family
      history of diabetes. METHODS: A prospective study was undertaken of incident
      cases of type 1 diabetes using an active monthly reporting card system from
      January 1, 1997 to December 31, 1998 in the Republic of Ireland. Follow-up
      questionnaires were distributed to pediatricians nationally. RESULTS: Two hundred
      and eighty-three incident cases were identified. Polyuria, polydipsia and weight
      loss were the main presenting symptoms in all age categories. Nocturnal enuresis
      was reported in 19% under 5 yr and in 31% aged 5-9.99 yr. Constipation was noted
      in five patients and in 10.4% under 5 yr of age. The median duration of symptoms
      was highest in the youngest (under 2 yr) and oldest (10-14.99 yr) age categories.
      Presentation in moderate/severe DKA occurred in 25% overall and six of nine of
      those aged under 2 yr. A family history of type 1 diabetes in a first-degree
      relative was found in 10.2%. CONCLUSIONS: This study confirms the abrupt onset of
      type 1 diabetes, the absence of a family history, and the importance of the
      classical symptoms of polyuria, polydipsia, and weight loss in the majority of
      cases. It reveals secondary enuresis as an important symptom, especially in those
      under 10 yr, and constipation in the under 5 yr age group. The very young (under
      2 yr) are more difficult to diagnose, have more variability of symptom duration,
      and are more likely to present in moderate/severe DKA. A high index of suspicion
      aids early diagnosis.

PMID- 15963034
TI  - Increased incidence and severity of diabetic ketoacidosis among uninsured
      children with newly diagnosed type 1 diabetes mellitus.
AB  - OBJECTIVES: (a) To determine the incidence and severity of diabetic ketoacidosis
      (DKA) and (b) to stratify according to insurance status at the initial diagnosis
      of type 1 diabetes (T1DM). RESEARCH DESIGN AND METHODS: Subjects included
      children <18 yr who presented with new-onset T1DM from January 2002 to December
      2003 and were subsequently followed at the Barbara Davis Center. Insurance status
      and initial venous pH were obtained. RESULTS: Overall, 383 subjects presented
      with new-onset T1DM and 359 (93.7%) were enrolled. Forty-three (12.0%) of these
      children were uninsured and 40 (11.1%) had Medicaid. One hundred and two (28.4%)
      subjects presented with DKA. When compared to the insured subjects, uninsured
      subjects had a significantly increased risk of presenting with DKA [odds ratios
      (OR): 6.19, 95% CI 3.04-12.60, p < 0.0001], as well as presenting with severe
      DKA, defined as venous pH <7.10 (OR: 6.09, 95% CI 3.21-11.56, p < 0.0001). There
      were no differences, however, between the insured and Medicaid subjects in their
      probability of presenting with DKA or severe DKA. The risk of presenting with DKA
      (as well as with severe DKA) was the highest among patients <4 yr old.
      CONCLUSIONS: At the time of initial diagnosis, uninsured patients were more
      likely to present with DKA than insured patients. Furthermore, when the uninsured
      subjects presented with DKA, the condition tended to be more severe and life
      threatening. A potential explanation is that uninsured subjects may delay seeking
      timely medical care, thereby presenting more critically ill, whereas insured
      subjects may have their T1DM diagnosed earlier.

PMID- 15963035
TI  - Neuropsychiatric disorders at the presentation of type 2 diabetes mellitus in
      children.
AB  - OBJECTIVES: To estimate the frequency of neuropsychiatric disease (NPD) in an
      urban pediatric type 2 diabetes mellitus (T2DM) population, to compare
      demographic characteristics of affected patients with those unaffected with NPD,
      and to determine the frequency of psychotropic medication treatment. STUDY
      DESIGN: Retrospective chart review of patients with T2DM at the Children's
      Hospital of Philadelphia. RESULTS: Of 237 patients with T2DM, 46 (19.4%) were
      found to have NPD at the presentation of diabetes. Diagnoses by report included
      depression, attention-deficit hyperactivity disorder (ADHD), neurodevelopmental
      disorders, schizophrenia, and bipolar disorder. Those affected were 63% females
      and 37% males, with a mean age of 14.6 yr and body mass index (BMI) of 34.3
      kg/m(2) at diagnosis of T2DM. Patients were 79% African American, 13% Caucasian,
      4.3% Hispanic, and 4.3% Asian. There were no statistically significant
      differences in demographic characteristics or BMI between those affected and
      unaffected with NPD. Twenty-nine patients (63%) were on psychotropic medication
      and were prescribed 58 medications, most commonly mood stabilizers (n = 20) and
      atypical antipsychotics (n = 17). CONCLUSIONS: Our data reveal a high frequency
      of NPD among pediatric patients with T2DM at presentation to a tertiary care,
      urban medical center. Many affected patients are receiving psychotropic
      medication. These data have implications for screening regimens for pediatric
      populations at high risk for T2DM and for therapeutic interventions, including
      lifestyle measures.

PMID- 15963036
TI  - Diabetic ketoacidosis, hyperosmolarity and hypernatremia: are high-carbohydrate
      drinks worsening initial presentation?
AB  - The case of five pediatric patients who presented to the Royal Children's
      Hospital, Melbourne with newly diagnosed diabetes mellitus between January 2001
      and September 2003 is reported. Each case was complicated by hyperosmolarity and
      hypernatremia and required intensive therapy. Fluid intake prior to admission in
      each case was documented and consisted of between 5 and 12 L of carbonated
      carbohydrate beverages and 'isotonic' sports drinks. At presentation, biochemical
      results of the four cases (four males and one female), mean age 13.6 yr (range
      11.7-15.1 yr) included glucose (mean 1460 mg/dL; range 864-2106), adjusted sodium
      (mean 176.3 mmol/L; range 165-183), serum osmolarity (mean 399 mmol/kg; range 364
      424), anion gap (mean 48 mEq/L; range 42-84), and pH (mean 7.15; range 7.01
      7.27). All five cases had evidence of ketonuria on presentation. Treatment in all
      five cases consisted of replacement of fluids over a prolonged period of 72 h and
      careful monitoring of electrolyte response. Three of five cases required
      hemofiltration in the first 48 h postadmission. All five cases made a complete
      recovery without neurological sequelae. Carbonated carbohydrate fluid intake may
      precipitate a more severe presentation of type 1 diabetes mellitus (T1DM). Fluid
      composition and intake should be carefully estimated at admission to help
      identify and manage similar cases.

PMID- 15963037
TI  - Progression from normal glucose tolerance to type 2 diabetes in a young girl:
      longitudinal changes in insulin sensitivity and secretion assessed by the clamp
      technique and surrogate estimates.
AB  - The pathophysiology of type 2 diabetes (T2DM) involves insulin resistance and
      relative insulin deficiency in at-risk youth. We-report longitudinal changes in
      insulin sensitivity and secretion in a high-risk African-American youth with
      obesity and polycystic ovary syndrome who progressed from normal glucose
      tolerance to impaired glucose tolerance to T2DM within 5 yr. This report
      demonstrates that in our patient: (i) insulin resistance was the pre-existing
      abnormality, but it was the marked decline in insulin secretion which led to T2DM
      and (ii) surrogate estimates of insulin sensitivity using fasting glucose and
      insulin concentrations were not reliable indices in reflecting the changes in in
      vivo insulin sensitivity in this case.

PMID- 15963038
TI  - Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of
      African-American children?
AB  - Adiponectin is an adipocytokine with antidiabetogenic properties. The present
      study investigated: (i) the effect of race on adiponectin levels and (ii) the
      relationship of adiponectin levels in children to insulin sensitivity and
      secretion. Fasting adiponectin levels were determined in 22 healthy prepubertal
      black compared with 22 white children of similar body composition. We previously
      reported these black children to have lower insulin sensitivity and higher first
      phase insulin secretion than their white peers. Fasting adiponectin levels were
      lower in black children (9.9 +/- 1.0 microg/mL vs. 15.7 +/- 1.1 microg/mL, p <
      0.001). Adiponectin correlated positively with insulin sensitivity (r = 0.29, p =
      0.06) and negatively with first-phase insulin levels (r = -0.47, p = 0.001). In a
      multiple regression analysis, 48% of the variance in first-phase insulin
      secretion was explained by the independent effects of race (p = 0.017),
      adiponectin (p = 0.03), and percentage of body fat (p < 0.001). Adiponectin did
      not contribute significantly to the variance in insulin sensitivity. In summary,
      black children have approximately 35% lower adiponectin levels than their white
      peers. Lower adiponectin does not seem to explain the racial differences in
      insulin sensitivity. The relationship of hyperinsulinemia and hypoadiponectinemia
      needs to be further explored.

PMID- 15963039
TI  - From congenital hyperinsulinism to diabetes mellitus: the role of pancreatic beta
      cell KATP channels.
AB  - Pancreatic beta-cell adenosine triphosphate (ATP)-sensitive potassium (K(ATP))
      channels play a pivotal role in linking glucose metabolism to regulated insulin
      secretion. K(ATP) channels are hetero-octameric complexes comprising two subunits
      Kir6.2 and sulfonylurea receptor 1 (SUR1). Changes in the intracellular
      concentration of nucleotides (ATP) cause alterations in the resting and opening
      state of the K(ATP) channels. Loss-of-function mutations in the genes encoding
      the two subunits of K(ATP) channels lead to the most common form of congenital
      hyperinsulinism (CHI). This causes persistent and severe hypoglycemia in the
      neonatal and infancy period. CHI can cause mental retardation and epilepsy if not
      treated properly. On the other hand, now there is evidence of an association
      between polymorphisms in the Kir6.2 gene and type 2 diabetes mellitus, mutations
      in the Kir6.2 gene and neonatal diabetes mellitus, and mutations in the SUR1 gene
      and diabetes mellitus. Interestingly, for reasons that are unclear at present,
      mice knockout models of K(ATP) channels are different from the human phenotype of
      CHI. This article is a review focusing on how abnormalities in the pancreatic
      beta-cell K(ATP) channels can lead to severe hypoglycemia on the one hand and
      diabetes mellitus on the other.

PMID- 15963041
TI  - A commentary on the Zinkernagel-Hengartner 'Credo 2004'.
AB  - In 'Credo 2004', Zinkernagel and Hengartner give us a food-for-thought analysis
      of immune responsiveness based on a 'pragmatic and empiric point of view.' The
      Credo 2004 postulates derived by inductive extrapolation from observation to
      generalization do not satisfactorily account for immune behaviour because they
      lack a conceptualization as illustrated here. Nevertheless, Credo 2004 is
      certainly valuable in a limited framework because it is based on the most likely
      of assumptions namely that the immune system was evolutionarily selected to
      protect against infectious agents, and therefore the study of pathogens will most
      accurately reveal how the immune system responds normally to protect. After
      reformulating them, the postulates of Credo 2004 are analysed with respect to
      their generality.

PMID- 15963043
TI  - Upregulation of Bcl-2 at the foetal-maternal interface from mice undergoing
      abortion.
AB  - Several burning questions remain unanswered in pregnancy-related research. Pro-
      and anti-inflammatory cytokines orchestrate an intriguing interaction leading
      either to the development of a normal individual or to its rejection. Augmented
      Th1 cytokines' production is involved in immunological rejection of the foetus.
      Excessive production of Th1 cytokines, particularly of tumour necrosis factor
      (TNF)-alpha, also triggers apoptosis. Thus, in the present work we investigated
      the incidence of apoptosis in a well-known experimental model of Th1-induced
      abortion, characterized by increased local TNF-alpha levels. Apoptosis of
      lymphocytes as well as their Th1 and Th2 cytokine production were analysed by
      flow cytometry. TNF-alpha mRNA levels were additionally analysed by real time
      reverse transcription-polymerase chain reaction (RT-PCR) in placental and
      decidual samples. Total placental apoptosis activity was investigated by
      measuring caspase-3 activity and by TdT-mediated dUTP nick end label staining.
      Immunohistochemistry, Western blot and real time RT-PCR were used to localize and
      quantify several anti- and pro-apoptotic molecules at the foetal-maternal
      interface. Despite elevated Th1 levels at the foetal-maternal interface, mice
      undergoing abortion presented comparable apoptotic rates. Interestingly, we found
      a significant upregulation of the anti-apoptotic Bcl-2 protein at the foetal
      maternal interface from abortion-prone mice, while no changes could be observed
      for pro-apoptotic molecules. In the light of our results, we conclude that there
      is no evidence of increased apoptosis in mice undergoing immunological abortion
      in spite of elevated TNF-alpha levels. This is probably due to a selective
      upregulation of anti-apoptotic pathways (i.e. Bcl-2) at the foetal-maternal
      interface as a compensatory and/or protective mechanism.

PMID- 15963044
TI  - Immunoglobulin-A antibodies in upper airway secretions may inhibit intranasal
      influenza virus replication in mice but not protect against clinical illness.
AB  - Mice immunized intranasally with a formalin-inactivated A/PR/8/34 (H1N1)
      influenza whole virus vaccine adjuvanted with cholera toxin, outer membrane
      vesicles from group B meningococci or formalin-inactivated whole cell Bordetella
      pertussis were protected against replication of the homologous virus in the nasal
      cavity. Only some mice were protected against clinical illness measured as weight
      loss and lowered body temperature. All mice immunized subcutaneously with one
      tenth the intranasal vaccine dose without adjuvant were protected against
      clinical illness but not against local mucosal viral replication. Replicating
      virus was primarily found in animals with low concentrations of immunoglobulin
      (Ig)-A antibodies in saliva regardless of concentrations of IgG antibodies in
      serum. Clinical illness was seen only in those with low serum antibodies
      regardless of antibody levels in saliva. Nonreplicating nasal vaccines may not be
      sufficiently protective unless they also have a substantial influence on systemic
      immunity.

PMID- 15963045
TI  - Expression of the virulence factor, BfpA, by enteropathogenic Escherichia coli is
      essential for apoptosis signalling but not for NF-kappaB activation in host
      cells.
AB  - Localized adherence (LA) of enteropathogenic Escherichia coli (EPEC) to
      epithelial cells results in attaching and effacing of the surface of these cells.
      LA depends on the gene bfpA, which codes for the BfpA protein. We found that EPEC
      E. coli adherence factor (EAF)((+)), expressing BfpA, significantly reduced HeLa
      cell viability in comparison with EPEC-EAF((-)), as evaluated by the
      mitochondrial-dependent succinate dehydrogenase conversion of 3'-[4,5,
      dimethylthiazol-2yl]2,5-diphenyltetrazolium bromide (MTT) to its formazan.
      Apoptosis accounts for a substantial loss of the cell viability, because the
      cells incubated with EPEC-EAF((+)) or with cloned BfpA (data not shown), but not
      with EPEC-EAF((-)), were positive for annexin-V binding, demonstrated chromatin
      condensation and nuclei fragmentation and exhibited a high level of caspase-3
      activity. Because the blockade of bacterial cell-surface-associated BfpA by anti
      BfpA immunoglobulin (Ig)Y antibody suppressed apoptotic death induced by EPEC
      EAF((+)), BfpA may be the trigger for apoptosis. Both EPEC-EAF((+)) and EPEC
      EAF((-)), as well as recombinant BfpA (data not shown), activated nuclear factor
      (NF)-kappaB in a similar manner as analysed by the electrophoretic mobility shift
      assay (EMSA). EMSA supershift analysis demonstrated the presence of p65/RelA in a
      DNA-binding complex. In contrast to DNA binding, NF-kappaB-dependent reporter
      gene transactivation was stimulated more strongly by EPEC B171/EAF((+)),
      suggesting a role for this virulence factor in the regulation of transcriptional
      activity of NF-kappaB. Because suppression of NF-kappaB activation by BAY11-7085,
      a NF-kappaB inhibitor, neither induced apoptosis by itself nor blocked apoptosis
      induction by EPEC-EAF((+)), it may be suggested that apoptosis is not regulated
      by the NF-kappaB pathway in HeLa cells.

PMID- 15963046
TI  - CD45RA and RO isoforms have distinct effects on cytokine- and B-cell-receptor
      mediated signalling in human B cells.
AB  - The common leucocyte antigen, CD45, is widely expressed on the surface of
      lymphocytes. In T and B cells, CD45 has an important role in the early events of
      receptor signalling. However, the role of various CD45 isoforms in B-cell
      receptor (BCR)- and cytokine-induced signalling and proliferation is still
      unclear. In the present study, we establish two follicular lymphoma cell lines
      expressing either CD45RA (HF28RA) or CD45R0 (HF28R0) isoforms. It was observed
      that the two isoforms had distinct effects on BCR- or cytokine-induced cellular
      proliferation. BCR stimulation significantly increased the proliferation of
      HF28R0 cells, in contrast to a decreased proliferation of HF28RA cells. Moreover,
      proliferation of HF28R0 cells significantly increased after the addition of
      interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12, IL-13, IL-15, interferon-gamma
      and tumour necrosis factor-alpha cytokines, whereas most of these cytokines
      significantly inhibited the proliferation of HF28RA cells. In addition, the cell
      lines had their individual cytokine mRNA expression profiles after BCR
      stimulation. We also analysed the effect of CD45 isoforms on intracellular
      signalling after BCR stimulation. It was found out that the kinetics of ERK1/2
      MAP kinase phosphorylation was clearly faster in HF28R0 than in HF28RA cells. The
      phosphorylation of other analysed MAP kinases or PTKs was very similar in the
      cell lines.

PMID- 15963047
TI  - A full flora, but not monocolonization by Escherichia coli or lactobacilli,
      supports tolerogenic processing of a fed antigen.
AB  - Fed protein undergoes processing and coupling to major histocompatibility complex
      (MHC) II molecules during passage through the intestinal epithelium, generating a
      tolerogenic form of the antigen in serum. Transfer of this factor to naive
      animals induces tolerance in the recipient. In this study, we investigate what
      impact colonization with Gram-positive (Lactobacillus plantarum) or Gram-negative
      (Escherichia coli) bacteria has on tolerogenic processing in the gut. Germ-free
      (GF), monocolonized or conventional mice were fed ovalbumin (OVA), and their
      serum was collected and transferred to naive conventional recipients that were
      tested for delayed-type hypersensitivity against OVA after parenteral
      immunization. A transferable tolerogenic factor was produced by conventional
      mice, but not by mice that were germ free or monocolonized with either E. coli or
      L. plantarum. Conventional, but neither GF nor monocolonized mice showed
      upregulation of MHCII expression in the epithelium of small intestine. The
      results suggest that a complex intestinal microflora is needed to support oral
      tolerance development.

PMID- 15963048
TI  - Infection of human endothelial cells with Staphylococcus aureus induces
      transcription of genes encoding an innate immunity response.
AB  - Staphylococcus aureus is a gram-positive bacterium frequently isolated from
      patients with bloodstream infections. Endothelial cells (EC) play an important
      role in host defence against bacteria, and recent reports have shown that
      infection of EC with S. aureus induces expression of cytokines and cell surface
      receptors involved in activating the innate immune response. The ability of S.
      aureus to invade nonphagocytic cells, including EC, has been documented. However,
      the knowledge of the role of EC in pathogenesis of S. aureus infection is still
      limited. In this study, we investigate the gene-expression program in human EC
      initiated by internalized S. aureus, using microarray analysis. We found 156
      genes that were differentially regulated at least threefold, using arrays
      representing 14,239 genes. Many of the upregulated genes code for proteins
      involved in innate immunity, such as cytokines, chemokines and cell adhesion
      proteins. Other upregulated genes encode proteins involved in antigen
      presentation, cell signalling and metabolism. Furthermore, intracellular bacteria
      survived for days without inducing EC death.

PMID- 15963049
TI  - Simultaneous expression and detection of multiple retroviral constructs in
      haematopoietic cells after bone marrow transplantation.
AB  - Due to the complexity and redundancy of molecular processes governing the
      development and function of haematopoietic cells, experimental procedures
      allowing simultaneous alteration in gene expression of multiple genes in vivo are
      needed. Here, we describe a protocol allowing for simultaneous transduction of
      haematopoietic stem cells (HSC) with two different replication incompetent
      retroviral expression vectors followed by transplantation of lethally irradiated
      recipient mice. These bicistronic retroviral vectors carried genes for the
      enhanced green and yellow florescent proteins (EGFP and EYFP) respectively.
      Spleen cells from reconstituted animals were stained for common lymphocyte and
      myeloid markers, then analysed on a two-laser, 488 and 635 nm, flow cytometer
      equipped with a 510/20-nm bandpass filter for FL1, a 550/30-nm bandpass filter
      for FL2 and a 530-nm short-pass dichroic mirror. It was demonstrated that cells
      expressing EGFP, EYFP or combinations thereof could be distinguished and analysed
      for staining with PerCP- and APC-conjugated reagents. We found that a sizable
      proportion of cells (70%) from reconstituted animals expressed EGFP and/or EYFP
      and that expression of these genes did not affect lymphoid or myeloid
      development. We also demonstrated that the alternative optical configuration
      allowed for conventional multiparameter flow cytometric analyses.

PMID- 15963050
TI  - Milk-derived GM(3) and GD(3) differentially inhibit dendritic cell maturation and
      effector functionalities.
AB  - Gangliosides are complex glycosphingolipids, which exert immune-modulating
      effects on various cell types. Ganglioside GD(3) and GM(3) are the predominant
      gangliosides of human breast milk but during the early phase of lactation, the
      content of GD(3) decreases while GM(3) increases. The biological value of
      gangliosides in breast milk has yet to be elucidated but when milk is ingested,
      dietary gangliosides might conceptually affect immune cells, such as dendritic
      cells (DCs). In this study, we address the in vitro effect of GD(3) and GM(3) on
      DC effector functionalities. Treatment of bone marrow-derived DCs with GD(3)
      before lipopolysaccharide-induced maturation decreased the production of
      interleukin-6 (IL-6), IL-10, IL-12 and tumor necrosis factor-alpha as well as
      reduced the alloreactivity in mixed leucocyte reaction (MLR). In contrast, only
      IL-10 and IL-12 productions were significantly inhibited by GM(3,) and the
      potency of DCs to activate CD4(+) cells in MLR was unaffected by GM(3). However,
      both gangliosides suppressed expression of CD40, CD80, CD86 and major
      histocompatibility complex class II on DCs. Because GD(3) overall inhibits DC
      functionalities more than GM(3), the immune modulating effect of the ganglioside
      fraction of breast milk might be more prominent in the commencement of lactation
      during which the milk contains the most GD(3).

PMID- 15963051
TI  - Bioactivation of latent transforming growth factor beta1 by Mycobacterium
      tuberculosis in human mononuclear phagocytes.
AB  - Biologically active transforming growth factor beta 1 (TGFbeta1) has been
      identified at sites of Mycobacterium tuberculosis (MTB) infection in the lung;
      however, the underlying mechanism(s) for its activation is not clear. Here using
      an enzyme-linked immunospot assay for TGFbeta1, we show that human blood
      monocytes (MN) and alveolar macrophages (AM) produce bioactive TGFbeta1 upon
      stimulation by MTB. However, only MTB-stimulated MN increased TGFbeta1 production
      on a per cell basis. The frequency of TGFbeta1-producing MN was reduced by an
      inhibitor of plasmin, bdellin, indicating a role for plasmin pathways in the
      bioactivation of cytokine. The expression of urokinase plasminogen activator
      receptor (uPAR) mRNA and both surface and soluble uPAR (CD87) was increased in
      MTB-activated MN. However, antibody neutralization of uPAR suppressed bioactive
      TGFbeta1 in MN alone. Thus, the more immature MN, which are continuously
      recruited to the lung during tuberculosis (TB), have a higher capacity to
      bioactivate TGFbeta1 by expression of components of the plasmin pathway. Excess
      production and bioactivation of TGFbeta1 at sites of MTB infection may undermine
      host immune responses during TB.

PMID- 15963052
TI  - Normal ICOS, ICOSL and AID alleles in Danish patients with common variable
      immunodeficiency.
AB  - Common variable immunodeficiency, CVID, is a primary antibody deficiency
      characterized by decreased levels of serum immunoglobulin G (IgG), decreased IgA
      and/or IgM and recurrent infections. It is assumed to be heterogeneous group of
      disorders caused by different genetic defects. Some patients have decreased
      levels of class switched memory B cells and/or decreased levels of somatic
      hypermutation which points to defects in the germinal centre (GC) reactions as
      cause of the disease in these patients. The inducible costimulator, ICOS, and
      its' ligand, ICOSL, are both involved in and necessary for the GC reaction and so
      is activation-induced cytidine deaminase, AID. Therefore, we sequenced the ICOS,
      ICOSL and AID genes in a cohort of 34 Danish CVID patients. We found 13 new
      single nucleotide polymorphisms (SNP) in the intron regions of the ICOSL gene as
      well as one SNP in exon 3. However, none of these polymorphisms were associated
      with CVID. We did not find a previously reported CVID-causing ICOS gene deletion
      or any other unique mutations in the ICOS or AID genes.

PMID- 15963053
TI  - Responses to free lipopolysaccharide and Escherichia coli by normal human
      intestinal macrophages, following their migration out of the lamina propria.
AB  - Intestinal macrophage responses to luminal bacteria and their constituents are
      important in mucosal inflammatory responses. We investigated the responses of
      intestinal macrophages to free lipopolysaccharide (LPS) and Escherichia coli.
      Macrophages were isolated from normal terminal ileum and colon by allowing them
      to migrate out of the lamina propria of mucosal samples denuded of epithelial
      cells. Following exposure to free LPS or fluorescein-labelled E. coli,
      responsiveness was studied by intracellular expression of tumour necrosis factor
      alpha (TNF-alpha). CD14, CD33, CD68, TLR2 and TLR4 expression was studied by
      fluorescence-activated cell sorter (FACS). TLR and NOD2 expression was confirmed
      by reverse-transcriptase polymerase chain reaction (RT-PCR). CD14 was expressed
      by 36.5 +/- 4.0% of the macrophages obtained following migration out of the
      lamina propria. These cells also expressed TLR2, TLR4 and NOD2. Of cells exposed
      to free LPS or those that had taken up E. coli, a greater proportion of CD14(+)
      than CD14(-) macrophages expressed intracellular TNF-alpha. Moreover, a greater
      proportion of macrophages (CD14(+) and CD14(-)) demonstrated responses to E. coli
      than free LPS. In conclusion, a proportion of macrophages obtained following
      migration out of the lamina propria of normal terminal ileal and colonic mucosal
      samples express CD14, TLR2 and TLR4. These cells respond to free LPS and E. coli,
      as demonstrated by the expression of TNF-alpha.

PMID- 15963054
TI  - Skeletal morbidity in childhood acute lymphoblastic leukaemia.

PMID- 15963055
TI  - Mutations within the transcription factor PROP1 are rare in a cohort of patients
      with sporadic combined pituitary hormone deficiency (CPHD).
AB  - OBJECTIVE: Mutations within the pituitary-specific paired-like homeobox gene
      PROP1 have been described in 50-100% of patients with familial combined pituitary
      hormone deficiency (CPHD). We screened a cohort of sporadic (n = 189) and
      familial (n = 44) patients with hypopituitarism (153 CPHD and 80 isolated hormone
      deficiencies) for mutations within the coding sequence of PROP1. DESIGN AND
      PATIENTS: Patients with congenital hypopituitarism were recruited from the London
      Centre for Paediatric Endocrinology as well as several national and international
      centres. The pituitary phenotype ranged from isolated growth hormone deficiency
      (IGHD) to panhypopituitarism. Clinical data, including endocrine and neuro
      radiological studies were obtained from patient records, and DNA was collected
      and screened for mutations within PROP1 using PCR and single-stranded
      conformation polymorphism (SSCP) analysis. Positive results on SSCP were
      sequenced directly. RESULTS: The prevalence of PROP1 mutations in unselected
      sporadic cases of hypopituitarism was lower (1.1%) than in familial cases
      (29.5%). PROP1 mutations can be associated with a highly variable phenotype, and
      both pituitary hypoplasia and pituitary hyperplasia. We describe the waxing and
      waning of a pituitary mass over 20 months in association with a PROP1 mutation
      that is predicted to lead to complete loss of function. Additionally, we have
      identified a possible founder mutation in CPHD patients from the Indian
      subcontinent. CONCLUSIONS: PROP1 mutations are rare in sporadic cases of CPHD,
      although the prevalence rises if there is a positive family history or if the
      patients are carefully selected with respect to the endocrine and
      neuroradiological phenotype. There is considerable phenotypic variability in
      families with the same mutation, indicating the role of other genetic or
      environmental factors on phenotypic expression. Finally, the pituitary
      enlargement that is observed in patients with PROP1 mutations can wax and wane in
      size before eventual involution.

PMID- 15963056
TI  - Efficacy of ACE-inhibitor therapy on renal disease in glycogen storage disease
      type 1: a multicentre retrospective study.
AB  - BACKGROUND: The efficacy of ACE-inhibitors in decreasing microalbuminuria and
      proteinuria has been reported in a few patients with glycogen storage disease
      type 1 (GSD1); however, no case-control study has ever been published. AIM: The
      aim of the current study was to evaluate the efficacy of ACE-inhibitors in
      reducing glomerular hyperfiltration, microalbuminuria and proteinuria, and in
      delaying the progression of renal damage. PATIENTS AND METHODS: Ninety-five
      patients (median age at the time of the study: 14.5 years) were enrolled from
      nine Italian referral centres for metabolic diseases. A retrospective study of a
      10-year follow-up was conducted in order to compare the evolution of these
      parameters in treated patients with those who were not treated with ACE
      inhibitors. RESULTS: A significant and progressive decrease of glomerular
      filtration rate was observed in treated patients vs. those who were not treated
      with ACE-inhibitors (P < 0.05). No difference was observed for microalbuminuria
      and proteinuria between the two groups of patients. Moreover, the ACE-inhibitors
      significantly delayed the progression from glomerular hyperfiltration to
      microalbuminuria, but not that from microalbuminuria to proteinuria. CONCLUSIONS:
      The results of the present study underline the importance of a strict follow-up
      of renal function in GSD1 patients. The detection of glomerular hyperfiltration
      suggests precocious initiation of ACE-inhibitor treatment to delay the
      progression of renal damage. A randomized prospective study is needed to
      establish for certain the real effectiveness of this treatment in GSD1 patients.

PMID- 15963057
TI  - Long-term remission following withdrawal of dopamine agonist therapy in subjects
      with microprolactinomas.
AB  - OBJECTIVE: Reports suggest that up to 70% of patients with microprolactinomas
      treated with dopamine agonist therapy may achieve long-term normoprolactinaemic
      remission following drug withdrawal. Yet, there is no consensus on the duration
      of therapy nor is therapeutic interruption universally practised. We have
      assessed remission rates in a large cohort of treatment-naive subjects with
      microprolactinomas. Subjects received dopamine agonist (DA) therapy with either
      cabergoline or bromocriptine for a period of 2 to 3 years in the majority of
      cases, followed by a trial of treatment withdrawal. DESIGN: Retrospective
      analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women
      and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or
      bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years.
      RESULTS: Following withdrawal of therapy, 57 subjects developed recurrence (64%)
      and the mean time to recurrence was 9.6 months (range 1-44 months), while 32
      subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7
      years). There was no difference in remission rates between subjects treated with
      cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship
      between pretreatment prolactin concentration and risk of recurrent symptomatic
      hyperprolactinaemia was observed. No subjects developed clinical features to
      suggest tumour expansion following therapeutic discontinuation. CONCLUSIONS: This
      study confirms that abrupt withdrawal of chronic dopamine agonist therapy,
      following 2 to 3 years of treatment is safe and associated with long-term
      remission in 30-40% of subjects with microprolactinomas. This therapeutic
      strategy is convenient and applicable in clinical practice.

PMID- 15963058
TI  - Short-term testosterone supplementation does not activate GH and IGF-I production
      in postmenopausal women.
AB  - BACKGROUND: Testosterone (Te), oestradiol, GH and IGF-I concentrations fall in
      postmenopausal women. OBJECTIVE: To test the effect of increased Te availability
      on impoverished GH/IGF-I secretion in this context. DESIGN/PATIENTS: Placebo (Pl)
      and a low vs. high dose of Te were administered transdermally for 7 days to each
      of 15 healthy older women (ages 48-81 years) in a randomized, double-blind
      crossover design. MEASUREMENTS: Frequent blood sampling, GHRP-2 (Growth hormone
      releasing peptide-2) infusion, and deconvolution analysis were used to assess GH
      secretion. RESULTS: Graded Te supplementation increased serum Te concentrations
      (nmol/l) from 0.87 +/- 0.06 [Pl] to 5 +/- 1 [low] and 7.3 +/- 1.6 [high] (P <
      0.001), but did not affect: (i) pulsatile GH secretion (microg/l/12 h; conversion
      factor: 1 microg/l = 0.33 mU/l), 29 +/- 7.2, 32 +/- 5.6 and 27 +/- 4.9; (ii) GH
      regularity (approximate entropy), 0.52 +/- 0.05, 0.57 +/- 0.05 and 0.56 +/- 0.05;
      (iii) IGF-I concentrations (microg/l; conversion factor: 1 microg/l = 0.131
      nmol/l), 126 +/- 13, 135 +/- 15 and 141 +/- 13; (iv) IGFBP-3 (mg/l), 3.7 +/- 0.2,
      3.6 +/- 0.1 and 3.7 +/- 0.2; (v) IGFBP-1 (microg/l), 41 +/- 2.3, 44 +/- 3.8 and
      44 +/- 3.2; and (vi) the mass of GH secreted (microg/l/3 h) after GHRP-2
      injection, 123 +/- 27, 146 +/- 32 and 147 +/- 38. CONCLUSION: Up to 8-fold
      elevation of Te concentrations for 1 week in postmenopausal women does not
      detectably amplify GH secretion or action, thus indicating that low androgen
      availability is not a proximate acute mediator of hyposomatotropism in
      postmenopausal individuals.

PMID- 15963059
TI  - Postoperative treatment of clinically nonfunctioning pituitary adenomas with
      dopamine agonists decreases tumour remnant growth.
AB  - OBJECTIVE: There is no consensus as to the optimal postoperative treatment of
      patients with clinically nonfunctioning pituitary adenomas (NFPA) in whom total
      tumour removal has not been achieved. In this study we assessed whether dopamine
      agonist (DA) treatment can prevent postoperative remnant enlargement in NFPA.
      DESIGN AND METHODS: Thirty-three patients (25 men/8 women; mean age, 61.7 +/-
      11.2 years; mean follow-up, 40.6 +/- 4.8 months) were treated with DA, and their
      outcome was compared to that of 47 untreated patients (33 men/14 women; mean age,
      59 +/- 2 years; mean follow-up, 42.9 +/- 4.2 months). RESULTS: Tumour mass
      decreased or remained stable in 18/20 patients in whom DA treatment was initiated
      upon detection of residual tumour on postoperative MRI (group I). In 13 subjects
      (group II), DA therapy was started when tumour remnant growth became evident
      during the course of routine follow-up. Tumour growth stabilized or decreased in
      8/13 (61.5%) of these patients. In contrast, tumour size remained stable in only
      38.3% (18/47) of the untreated subjects (P < 0.0001 for comparisons among the
      three groups) and increased in the remaining 29 patients. Tumour enlargement free
      mean survival time was 103.7 +/- 8.8 months (CI 86.3-121) for group I, 43.9 +/-
      9.6 months (CI 25.2-62.8) for group II and 36.7 +/- 3.8 (CI 29.2-44.2) for the
      control group (P = 0.0017). Treatment vs. control hazard ratio for tumour
      enlargement was 0.135 for group I (P = 0.007, 95% CI 0.032-0.577) and 0.892 for
      group II (P = 0.817; 95% CI 0.34-2.34). CONCLUSIONS: Dopamine agonist therapy is
      associated with a decreased prevalence of residual tumour enlargement in patients
      with nonfunctioning pituitary adenomas, particularly when treatment is instituted
      before tumour remnant growth is detected.

PMID- 15963060
TI  - Characterization of antipituitary antibodies targeting pituitary hormone
      secreting cells in idiopathic growth hormone deficiency and autoimmune endocrine
      diseases.
AB  - OBJECTIVE: In order to investigate whether somatotrophs are the target of
      antipituitary antibodies (APA) in adult patients with growth hormone deficiency
      (GHD), we studied the sera of 37 APA positive patients. PATIENTS: Patients were
      grouped as follows: nine patients with APA at high titre (> 1 : 8) affected by
      apparently idiopathic GHD; four of them (group 1a) with isolated GHD diagnosed
      during childhood and five with GHD diagnosed during adulthood associated with
      autoimmune endocrine diseases (group 1b), and 28 patients with autoimmune
      endocrine diseases without pituitary impairment, previously found positive for
      APA at low titre (1 : 8, group 2). MEASUREMENTS: APA were evaluated by a four
      layer double indirect immunofluorescence technique. RESULTS: In group 1a
      patients, APA immunostained exclusively GH-producing cells. In group 1b patients,
      APA were directed not only to GH- but also to other pituitary hormone-producing
      cells. In group 2 patients, APA were directed selectively to PRL-producing cells
      and rarely to some GH-producing cells. CONCLUSIONS: In the present study, we
      demonstrated that GH-secreting cells are the target of the autoimmune reaction in
      autoimmune GHD and that the immunostaining of only the somatotrophs is typical of
      isolated GHD. In contrast, the finding of diffuse staining of APA indicates the
      need to search for other autoimmune diseases. Finally, the presence of APA at low
      titre directed against PRL-secreting cells in patients with autoimmune endocrine
      diseases in the absence of pituitary impairment, seems to be only a nonspecific
      marker of pituitary autoimmunity. A longitudinal study would be useful to clarify
      the relationship between the different pituitary cell involvement and the natural
      history of pituitary dysfunction in autoimmune hypophysitis.

PMID- 15963061
TI  - Endogenous oestrogens are related to cognition in healthy elderly women.
AB  - OBJECTIVE: To investigate whether levels of endogenous hormones, in particular
      circulating oestrogens and SHBG, are associated with cognition in healthy
      postmenopausal women. DESIGN: Cross-sectional study. PATIENTS: Four hundred and
      two healthy postmenopausal women aged 50-74 years between 8 and 30 years after
      menopause, none taking oestrogen. MEASUREMENTS: Serum concentration of
      oestradiol, oestrone, and sex hormone binding globulin (SHBG) determined by
      immunoassay. Cognition assessed using the mini-mental state examination
      questionnaire (MMSE). RESULTS: In this group, 149 individuals had a MMSE score <
      27, while only 89 individuals had a MMSE score < 26, indicating a relatively
      healthy population with regard to cognitive ability. Cognition decreased with
      age, time since menopause and blood pressure, and was better with higher age at
      menopause. Serum oestrogens and SHBG levels were not related to age, age at
      menopause, or time since menopause, and oestrogen levels were positively
      associated with blood pressure. After adjustment for mean arterial pressure and
      SHBG, the frequency of mild cognitive impairment decreased significantly with
      higher oestradiol and oestrone serum levels [ORs Q5 vs. Q1: 0.41 (95% CI 0.20
      0.84) and 0.51 (95% CI 0.20-0.99) for oestradiol and oestrone, respectively].
      CONCLUSIONS: Postmenopausal women with higher remaining circulating oestradiol
      levels appear less likely to suffer from cognitive impairment. This effect is
      independent of age at menopause, time since menopause and BMI. These findings
      support the hypothesis that endogenous oestrogens may protect against cognitive
      decline with ageing.

PMID- 15963062
TI  - Correlation between genotype, phenotype and sex of rearing in 111 patients with
      partial androgen insensitivity syndrome.
AB  - OBJECTIVE: Partial androgen insensitivity syndrome (PAIS) is a heterogeneous
      group of intersex disorders characterized by a typical perineoscrotal
      hypospadias/micropenis phenotype, and a normal androgen-producing testis. Various
      mutations in the androgen receptor (AR) are known to cause PAIS. Phenotypic
      expression is widely variable and there are no agreed guidelines to determine the
      sex of rearing in individuals with borderline masculinization. We aimed to
      quantitatively assess the external genital phenotype in relation to AR genotype
      and sex of rearing and identify criteria that differentiate mutation positive
      (ARmt) from mutation negative (ARwt) PAIS patients. PATIENTS AND DESIGN: Cases
      with a diagnosis of PAIS were identified from the Cambridge Intersex Database. An
      external masculinization score (EMS) was used to quantify the degree of
      undermasculinization. Family history of AIS and details of the sex of rearing
      were recorded. Androgen binding was analysed in fibroblasts obtained from genital
      skin biopsies and mutational analysis of the AR was performed on genomic DNA
      extracted from peripheral blood. EMS and sex of rearing were compared in cases
      with similar mutations reported on the McGill International Database. RESULTS:
      Two hundred and sixty-three patients with PAIS were identified. Androgen receptor
      gene sequencing was performed in 111 patients. Twenty-seven (24%) had mutations.
      Family history of AIS was present in 61 and 21% of ARmt and ARwt patients,
      respectively. The median EMS was 3 in both groups. The majority of ARmt patients
      had abnormal binding and there was a tendency to a higher median testosterone
      rise on hCG stimulation in ARmt (9.3 nmol/l) compared with ARwt patients (6.9
      nmol/l). All patients with EMS of 4 or more were raised as male but there was an
      overlap of sex of rearing in patients with an EMS less than 4. A wide variation
      of EMS in relation to genotype and sex of rearing was observed. CONCLUSION: The
      phenotype in PAIS is extremely variable and is rarely predicted by the AR
      genotype. Apart from the family history, there are no specific criteria to
      differentiate ARwt from ARmt. Sex of rearing is not entirely dependent on the
      EMS. Cultural issues, other modifying genes and response to androgen trials might
      be influencing factors. Collaborative studies with uniform protocols are needed
      to investigate infants with PAIS. Documenting phenotype, surgical procedures and
      outcome criteria are necessary to enable decision-making on the sex of rearing in
      patients with a lower range EMS.

PMID- 15963063
TI  - Severe hypoleptinaemia associated with insulin resistance in patients with common
      variable immunodeficiency.
AB  - OBJECTIVE: Common variable immunodeficiency (CVI) is a primary immunodeficiency
      syndrome characterized by impaired production of antibodies and recurrent
      infections. Delay in diagnosis leads to metabolic wastage and low body weight.
      Leptin, a hormone produced by white adipose tissue, modulates insulin action by
      signal transduction cross-talk and by direct action on pancreatic beta-cells. We
      hypothesized that patients with CVI might present a defective regulation of
      leptin production and insulin resistance. PATIENTS: Thirteen CVI patients (39 +/-
      11 years) under gammaglobulin replacement were evaluated in parallel with 13
      gender-, age-, body weight- and body mass index (BMI)-matched healthy
      voluntaries, and with data from two large population series, the Bruneck and the
      Hoorn Studies. MEASUREMENTS: Serum leptin and insulin levels, homeostasis model
      assessment - insulin resistance (HOMA-IR), body composition, haematological,
      biochemical and immunoglobulin measurements were obtained. Data were analysed by
      a one-way analysis of variance (anova) and by Pearson's rank analysis. The
      institutional ethics committee approved the study, and informed consent was
      obtained from patients and controls. RESULTS: No differences were found between
      CVI and the control group when comparing gender distribution, age, body weight,
      BMI, waist/hip ratio, relative body fat and fasting glucose levels. Leptin levels
      were lower (P < 0.05) in CVI patients than in controls and lower than fasting
      leptin levels detected in a large population study. CVI patients' serum leptin
      levels did not correlate with BMI (r = 0.074, P = 0.8) and their high HOMA-IR
      indicated insulin resistance. CONCLUSIONS: CVI patients are relatively
      hypoleptinaemic and insulin resistant, and their serum leptin levels are not
      correlated to their BMI.

PMID- 15963064
TI  - Ambulatory blood pressure monitoring in patients with hyperthyroidism before and
      after control of thyroid function.
AB  - BACKGROUND AND OBJECTIVE: Thyroid hormones have pronounced effects on the
      cardiovascular system. Thyrotoxicosis affects blood pressure (BP), modifying both
      diastolic (DBP) and systolic (SBP) pressures. There are no studies examining BP
      with ambulatory blood pressure monitoring (ABPM) in hyperthyroidism before and
      after control of thyroid function. Our aims were (1) to analyse ABPM in a group
      of normotensive hyperthyroid patients before and after normalizing circulating
      thyroid hormones and (2) to compare these results with those obtained in a group
      of euthyroid subjects. PATIENTS AND MEASUREMENTS: We studied 20 normotensive
      hyperthyroid subjects [18 women; age (mean +/- SEM) 49.0 +/- 3.0 years] and 15
      healthy subjects. Patients were evaluated by ABPM over 24 h, at diagnosis and
      after therapy (n = 18). RESULTS: The average 24-h, daytime and night-time SBP was
      significantly greater in hyperthyroid patients than in controls with no
      significant differences in DBP. Circadian BP rhythm, estimated by the difference
      between mean values of SBP, DBP and mean BP during daytime and night-time, was
      unchanged. The average 24-h and daytime SBP significantly decreased after
      normalizing thyroid function in the 18 hyperthyroid evaluated patients. Daytime
      SBP and DBP were higher than night-time values both before and after control of
      thyroid function. However, no differences in circadian BP rhythm were observed.
      CONCLUSIONS: Normotensive hyperthyroid patients exhibit higher ambulatory SBP
      throughout 24 h than normotensive euthyroid subjects. Control of hyperthyroidism
      decreases ambulatory SBP values. Mean nocturnal fall in BP is comparable in
      normotensive hyperthyroid patients and control subjects.

PMID- 15963065
TI  - Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates
      ovarian growth.
AB  - OBJECTIVE: Ovarian enlargement is a constant feature of syndromes of extreme
      insulin resistance. The objective of this study is to show the role of insulin on
      ovarian growth in the presence of low gonadotropin levels. PATIENTS: Seven young
      patients with syndromes of extreme insulin resistance (five with lipodystrophy,
      one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied.
      MEASUREMENTS: Baseline LH concentrations and luteinizing hormone releasing
      hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide
      values were measured. Pelvic ultrasounds were performed. RESULTS: Four patients
      were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin
      levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM
      PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low
      gonadotropins that did not respond to LHRH stimulation test. All seven patients
      had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary.
      Testosterone values were increased in 4 of 7 patients. CONCLUSION: This
      represents the first example of the pathologic role of insulin to stimulate
      ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and
      steroidogenesis are normally stimulated by gonadotropins at puberty,
      hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic
      steroid profile that is active at all ages. We suggest that these patients
      constitute a model to separate the effect of insulin from gonadotropin in
      stimulating ovarian growth and/or steroidogenesis.

PMID- 15963067
TI  - Differentiated thyroid carcinoma with distant metastases at presentation:
      prognostic factors and outcome.
AB  - BACKGROUND: Differentiated thyroid cancer (DTC) presenting with distant
      metastases is uncommon. Prognostic factors that affect survival remain unclear.
      AIM: To evaluate factors influencing the survival of patients with DTC presenting
      with distant metastases. METHOD: A retrospective study of 111 patients (62 F, 49
      M) with DTC who presented with distant metastases (M1) treated at the Royal
      Marsden Hospital from 1940 to 2002. RESULTS: The median follow-up of living
      patients was 3.9 years (0.3-48) with a 10-year cause-specific survival rate of
      31%. Histology identified 46 papillary, 60 follicular and five Hurthle cell
      cancers. Sites of metastases comprised 54 lung (49%), 27 bone (24%), 21 multiple
      sites (19%) and nine with other single sites affected (8%). Near-total, total or
      completion thyroidectomy was performed in 56% of patients, radioiodine ablation
      in 76% and radioiodine therapy in 67%. External beam radiotherapy was given to 12
      patients and the same number received chemotherapy. Univariate analysis was
      performed with cause-specific survival as the main outcome measure. Age over 70,
      poorly differentiated tumours and Hurthle cell cancers were associated with worse
      outcomes (P < 0.01). Patients with multiple organ metastases had a worse survival
      (P = 0.02). Radical surgery did not significantly improve outcome compared to
      more conservative forms of surgery (subtotal thyroidectomy, hemi-thyroidectomy or
      lobectomy) but patients receiving radioiodine ablation and therapy had improved
      survival (P < 0.01). Multivariate analysis identified age over 70, poorly
      differentiated tumours and Hurthle cell variant to be the only independent
      factors associated with worse outcome (P < 0.01). Treatment in the 1991-2002 era
      was associated with an improved survival compared to all previous decades (P =
      0.009). CONCLUSIONS: Patients with DTC presenting with distant metastases have a
      worse outcome if aged over 70, have poorly differentiated tumours or have Hurthle
      cell variant. Despite their unfavourable prognosis, a dramatic improvement in
      survival was observed in the most recent era (1991-2002).

PMID- 15963066
TI  - The effects of growth hormone status on circulating levels of vascular growth
      factors.
AB  - BACKGROUND: Vascular growth factors are important not only in angiogenesis but
      also for the maintenance of normal endothelial integrity and function. Elevated
      levels of vascular endothelial growth factor (VEGF), angiopoietin-2, hepatocyte
      growth factor (HGF), endostatin and angiogenin have been associated with
      endothelial dysfunction and atherosclerosis. Both acromegaly and growth hormone
      deficiency (GHD) are associated with endothelial dysfunction and changes in blood
      vessel morphology. AIM: To investigate the effect of GH status on the circulating
      levels of angiogenic factors. DESIGN: We measured the levels of six endothelial
      growth modulators, four angiogenic growth factors and two inhibitors of
      angiogenesis in 35 untreated acromegalics, 36 untreated GH-deficient subjects and
      101 normal control subjects. Fifteen GH-deficient subjects were also studied
      before and 1 year after treatment with GH. RESULTS: Mean angiogenin
      concentrations were increased in acromegaly and decreased in GH-deficient
      subjects compared to control subjects. Endostatin levels showed a similar pattern
      although the elevated levels in acromegalic subjects did not achieve statistical
      significance. Angiogenin and endostatin levels both correlated significantly with
      IGF-I levels (R = 0.61, P < 0.001 and R = 0.22, P < 0.01, respectively). The
      relationship between angiogenin and IGF-I levels remained significant even after
      correction for gender, age, body mass index (BMI) and insulin resistance. There
      were no significant differences in the levels of HGF, VEGF, VEGF-C or
      angiopoietin-2 between the three groups. VEGF-D levels were elevated in both
      acromegalic and GH-deficient male subjects. A similar pattern was apparent in
      female subjects. After GH treatment, a significant reduction in VEGF-D levels and
      a significant rise in endostatin levels were observed in GH-deficient subjects. A
      nonsignificant increase in angiogenin levels was also observed. CONCLUSION: These
      data indicate that significant perturbations in the levels of vascular growth
      modulators are present in both acromegaly and GHD. While changes in endostatin
      and angiogenin levels appear to correlate with IGF-I levels, VEGF-D levels show
      similar perturbations in both acromegaly and GHD. Further studies are required to
      determine the relationship of the perturbations to endothelial dysfunction in
      these conditions.

PMID- 15963068
TI  - Gender differences in the relation of insulin-like growth factor binding protein
      1 to cardiovascular risk factors: a population-based study.
AB  - OBJECTIVE: A possible involvement of insulin-like growth factor-I (IGF-I) and its
      binding protein IGFBP-1 in the pathogenesis of cardiovascular disorder has been
      suggested. However, few publications have addressed the gender differences in
      cardiovascular risk factors in relation to the IGF/IGFBP system. The aim of the
      present study was to study gender differences in the relationship between fasting
      serum levels of IGFBP-1 and cardiovascular risk factors in a normal population of
      men and women. DESIGN: Cross-sectional study. Patients A normal population of 273
      men and women aged 20-74 years. MEASUREMENTS: A medical examination was performed
      and blood drawn in the morning after subjects had been fasting overnight. Before
      the examination, they were asked to fill out a questionnaire concerning lifestyle
      and psychosocial factors. RESULTS: Fasting IGFBP-1 was lower in men than in women
      and was positively correlated to age in men but not in women. The men had in
      general a more disadvantageous cardiovascular risk profile than women, with
      several indicators of the metabolic syndrome: higher blood pressure and higher
      serum levels of total cholesterol, triglycerides, low density lipoprotein
      cholesterol (LDL-C), plasma-glucose and insulin, as well as lower IGFBP-1. Women
      had lower physical activity, lower consumption of alcohol, and lower values on
      indicators of psychosocial and mental health but had a healthier diet. Our
      findings indicate that low circulating levels of IGFBP-1 are associated with the
      well-known risk factors of cardiovascular disease; however, the association
      showed a different pattern for men and women. In men we found a negative
      association with body mass index (BMI), insulin resistance and diastolic blood
      pressure, and a positive association with SHBG, cortisol and testosterone. For
      women low IGFBP-1 appears in negative associations with BMI, waist-hip ratio
      (WHR), insulin resistance and testosterone, and in positive associations with
      SHBG and cortisol. Significant gender differences in the correlation with IGFBP-1
      are seen for testosterone, cortisol, SHBG, WHR and oestradiol. For HDL-C and
      diastolic blood pressure the gender difference in correlation was at the limit of
      significance (P < 0.10). CONCLUSION: Low circulating levels of IGFBP-1 are
      associated with the well-known risk factors of cardiovascular disease; however,
      the association showed a different pattern for men and women. The most marked
      gender differences in the correlation with IGFBP-1 are seen for testosterone,
      cortisol, SHBG, WHR, oestradiol, HDL-C and diastolic blood pressure. Our study
      emphasizes the importance of separate analyses for men and women. The results
      presented are a step towards gaining a better understanding of the gender
      differences in cardiovascular disease and in the regulation of IGFBP-1, though
      further prospective studies are needed.

PMID- 15963069
TI  - Assessment of quality of life in patients with uncontrolled vs. controlled
      acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL).
AB  - OBJECTIVE: Acromegaly is a chronic disease with an important impact on quality of
      life. An acromegaly disease-generated quality of life questionnaire (AcroQoL) has
      recently been developed. We aimed to confirm reliability, construct validity and
      disease-specificity of the AcroQoL questionnaire. Second, we investigated the
      effect of remission status on health-related quality of life (HRQoL) in patients
      with acromegaly. DESIGN AND PATIENTS: Using a prospective, cross-sectional
      design, 33 patients with treated acromegaly and 22 patients with treated hormone
      inactive pituitary adenoma under stable replacement therapy completed the German
      version of the AcroQoL questionnaire. MEASUREMENTS AND RESULTS: Cronbach's alpha
      analysis showed high reliability of the total score and the different scales and
      subscales in patients with acromegaly (alpha ranging from 0.83 to 0.93, item
      total correlation 0.41-0.84). Patients with hormone-inactive pituitary adenoma
      showed lower reliability (alpha ranging from 0.17 to 0.75). Exploratory factor
      analysis in patients with acromegaly suggested a two-factorial solution with item
      distribution largely matching the scaling of the original Spanish questionnaire.
      Multiple regression analysis revealed significantly lower results of the total
      score and the different scales and subscales (indicating worse HRQoL) in patients
      with persistent acromegalic activity compared to patients with acromegaly in
      remission or discordant remission status. Consistently, IGF-I was an independent
      negative predictor of the different scores of the questionnaire. CONCLUSIONS: The
      AcroQoL questionnaire represents a reliable, construct valid and disease-specific
      tool for assessing health-related quality of life in patients with acromegaly.
      Patients with biochemically uncontrolled acromegaly showed significantly lower
      HRQoL than patients with acromegaly in remission or discordant remission status.

PMID- 15963070
TI  - Seladin-1/DHCR24 expression in normal ovary, ovarian epithelial and granulosa
      tumours.
AB  - OBJECTIVE: The human DIMINUTO/DWARF1 homolog seladin-1/DHCR24 has been recently
      reported to be up-regulated in adrenocortical adenomas. Seladin-1 expression has
      been reported in the normal ovary. Granulosa cell tumours of the ovary (GCT) as
      with adrenocortical adenomas arise from a steroidogenic tissue, respond to
      pituitary hormone stimulation and synthesize steroid hormones. DESIGN: To test
      the hypothesis that seladin-1 may also have a role in the pathogenesis of GCT, we
      determined the expression of seladin-1 in a cohort of GCT and in mucinous and
      serous cystadenocarcinomas and in normal ovary. MEASUREMENTS: Expression was
      determined by RT-PCR using gene specific primers and probes combined with
      Southern blot analysis of the PCR products. RESULTS: Seladin-1 expression was
      identified in the normal ovary, mucinous cystadenocarcinomas and serous
      cystadenocarcinomas of the ovary whereas no expression was observed in the GCT.
      CONCLUSIONS: Based on our results, seladin-1 is not expressed in the granulosa
      cells or at least not in those that give rise to GCT.

PMID- 15963071
TI  - Does an automated thyroid register improve the clinical management of hypothyroid
      patients? An observational study.

PMID- 15963072
TI  - Effectiveness of long-term rosiglitazone administration in patients with
      Cushing's disease.

PMID- 15963073
TI  - Hypopituitarism and rare dermatological diseases: an intriguing case of xanthoma
      disseminatum.

PMID- 15963074
TI  - Review article: practical management of inflammatory bowel disease patients
      taking immunomodulators.
AB  - Azathioprine, mercaptopurine, methotrexate, ciclosporin and tacrolimus all have
      their respective niches in the treatment of inflammatory bowel disease. These
      immunomodulators are potent and effective medications; however, they potentially
      have serious toxicity. To maximize benefit and minimize risk, clinicians must
      understand the mechanism of action, appropriate indications, range of toxicity
      and proper dosing of these medications. Furthermore, once initiating therapy,
      patients need to be monitored appropriately for evidence of efficacy and
      toxicity. This review includes the rationale behind recommendations for the
      management and monitoring of patients using immunomodulators. For the purine
      antagonists--azathioprine and mercaptopurine--the evidence for utility of
      thiopurine methyltransferase testing and mercaptopurine metabolite monitoring is
      addressed. The roles of liver biopsy and screening for methylenetetrahydrofolate
      reductase mutations in patients taking methotrexate are reviewed. With
      appropriate monitoring, the calcineurin inhibitors--ciclosporin and tacrolimus-
      can be used safely and effectively. Immunomodulators are important agents for the
      treatment of Crohn's disease and ulcerative colitis, and prescribing clinicians
      should be comfortable recognizing both their value and their limitations.

PMID- 15963075
TI  - Review article: the changing epidemiology of hepatocellular carcinoma in Canada.
AB  - The aim of this study was to examine the incidence of and mortality caused by
      hepatocellular carcinoma over the last 20 years in Canada, including the
      associated risk factors hepatitis C, diabetes and obesity. Databases from the
      Surveillance & Risk Assessment Division of Health Canada & Statistics Canada were
      analysed for trends in both age-adjusted incidence of and mortality due to
      hepatocellular carcinoma from 1984 to 2001. The epidemiological impact of
      hepatitis C, diabetes and obesity on hepatocellular carcinoma was also assessed.
      The incidence of hepatocellular carcinoma increased from 4.0 per 100,000 in 1984
      to 5.5 in 2,000 for males, and from 1.6 per 100,000 in 1984 to 2.2 in 2,000 for
      females. Mortality rates showed a 48% increase in males and 39% increase in
      females. The incidence of hepatitis C increased sharply in 1995 and remained
      elevated until 2,000 with an average value of 85.4 per 100,000 in males and 45.4
      per 100,000 in females. This increase is likely due to the widespread testing for
      hepatitis C. The prevalence of obesity and diabetes has increased in recent years
      and probably contributes to the increased incidence of hepatocellular carcinoma.
      The incidence of hepatocellular carcinoma in Canada has increased in the past 20
      years and is associated with a rise in the incidence of hepatitis C, obesity and
      diabetes.

PMID- 15963076
TI  - Review article: angiogenesis soluble factors as liver disease markers.
AB  - Angiogenesis is the formation of new blood vessels from pre-existing ones; it has
      been studied at the molecular level in different pathologies and is currently
      considered a promising novel therapeutic target in cancer. Recently, the use of
      angiogenesis soluble factors as markers of tumour growth has been investigated.
      The knowledge gained has led to test their use as therapeutic agents.
      Additionally, angiogenesis soluble factors could be used for the follow-up of
      pathologies that currently require monitoring with invasive techniques, like
      chronic viral hepatitis or renal and haematological diseases. The different
      factors have been described in multiple studies. In some cases, such as
      hepatocellular carcinoma, a potential use as prognostic markers has been
      suggested.

PMID- 15963077
TI  - Rifaximin dose-finding study for the treatment of small intestinal bacterial
      overgrowth.
AB  - BACKGROUND: Few controlled studies assessing choice and duration of antibiotic
      therapy for small intestinal bacterial overgrowth are available. AIM: To assess
      efficacy, safety and tolerability of different doses of rifaximin, a broad
      spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth
      eradication. METHODS: We enrolled 90 consecutive patients affected by small
      intestinal bacterial overgrowth. The presence of small intestinal bacterial
      overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above
      the basal value after 50 g glucose ingestion. Patients were randomized in three 7
      day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group
      2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1
      month after the end of therapy. Compliance to the treatment and incidence of side
      effects were also evaluated. RESULTS: No drop-outs were observed in the three
      groups. Glucose breath test normalization rate was significantly higher in group
      3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No
      significant differences in patient compliance and incidence of side-effects were
      found among groups. CONCLUSIONS: Higher doses of rifaximin lead to a significant
      gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth
      eradication without increasing the incidence of side-effects.

PMID- 15963078
TI  - Effect of hepatitis C infection on tacrolimus doses and blood levels in liver
      transplantation recipients.
AB  - BACKGROUND: In our cohort of patients with hepatitis-C virus, which is the most
      common indication for liver transplantation, we have noted higher relative blood
      levels of tacrolimus compared to patients without hepatitis-C virus. AIM: To
      verify this observation and determine its clinical significance, we performed a
      comparison of doses and blood levels of tacrolimus in hepatitis-C virus and non-
      hepatitis-C virus liver transplantation recipients. METHODS: Tacrolimus dose and
      trough level, as well as mean alanine aminotransferase, for all patients
      transplanted at our center with a deceased donor between 1/1995 and 12/1999 with
      hepatitis-C virus were recorded at monthly intervals during the first 24 months
      following transplantation and compared to patients without hepatitis-C virus.
      RESULTS: The tacrolimus levels for hepatitis-C virus and non-hepatitis-C virus
      patients were not significantly different at any of the monthly intervals, except
      month 9. In addition, the overall mean tacrolimus levels for hepatitis-C virus
      and non-hepatitis-C virus patients were not significantly different (P = ns).
      However, the mean tacrolimus dose (mg/kg) was significantly higher for hepatitis
      C virus patients at 12, 15, 18, 21 and 24 months, P < 0.01. The total mean
      tacrolimus dose in hepatitis-C virus patients was lower during year one by 39% (P
      = 0.018) and by 73% (P = 0.001) during year two. The total difference in cost of
      tacrolimus (for year one and two) administered to hepatitis-C virus patients was
      $4920, P = 0.03. The serum alanine aminotransferase was significantly higher in
      hepatitis-C virus patients at each monthly interval except month 1, P < or =
      0.01. CONCLUSIONS: Liver transplant recipients with hepatitis-C virus require
      significantly lower oral doses of tacrolimus to achieve the same blood levels
      compared to non-hepatitis-C virus patients. This difference may result in a
      significant reduction in the cost of tacrolimus in hepatitis-C virus patients.
      The most likely explanation for these findings is decreased hepatic clearance of
      tacrolimus caused by mild hepatic injury from recurrent hepatitis-C virus.

PMID- 15963079
TI  - A 10-day levofloxacin-based triple therapy in patients who have failed two
      eradication courses.
AB  - BACKGROUND: A standard third-line treatment is lacking, and European guidelines
      recommend performing culture in these patients. However, the use of this
      procedure as 'routine practice' is definitively not feasible. AIM: To evaluate
      the eradication rate of a 10-day levofloxacin-based triple therapy in patients
      who have failed two eradication courses for Helicobacter pylori. METHODS: A total
      of 151 patients with persistent Helicobacter pylori infection after two
      treatments were studied. Patients were considered positive if two of three
      endoscopic tests were positive. Susceptibility testing was also performed.
      Patients received a standard dose of proton-pump inhibitors twice daily,
      levofloxacin 250 mg twice daily and amoxicillin 1 g twice daily, for 10 days.
      Endoscopic follow-up was carried out 4-6 weeks after the end of eradication
      therapy. RESULTS: About 76% (95% CI: 68.8-82.3), and 85% (95% CI: 77.5-89.7) of
      patients were eradicated according to intention-to-treat and per-protocol
      analysis, respectively. Eradication rates of the strains showed as 92% (95% CI:
      83.2-96.7) of those resistant to both metronidazole and clarithromycin but
      susceptible to levofloxacin. CONCLUSIONS: In patients who failed previous
      regimens, the 10-day levofloxacin-based triple therapy is safe and effective,
      allowing eradication in almost 80% of the patients.

PMID- 15963080
TI  - Most Helicobacter pylori strains of Kolkata in India are resistant to
      metronidazole but susceptible to other drugs commonly used for eradication and
      ulcer therapy.
AB  - BACKGROUND: Helicobacter pylori infection is very common in India, as in other
      developing countries, but few data exist on the susceptibility of H. pylori to
      antimicrobial agents commonly used for eradication here. AIM: To determine the
      antimicrobial susceptibility of H. pylori strains from Kolkata, in eastern India.
      METHODS: A total of 67 H. pylori strains isolated from gastritis and peptic ulcer
      patients of Kolkata were examined in the study. Minimum inhibitory concentration
      to the antibiotics was determined by the agar dilution method. RESULTS: Most of
      the strains (85%) were resistant to at least 8 microg/mL of metronidazole and
      7.5% strains were resistant to tetracycline, which was high when compared with
      other reports in India. All Kolkata strains were highly sensitive to
      clarithromycin, furazolidone and amoxicillin. CONCLUSIONS: Our results differed
      significantly from the few available reports on drug sensitivity profile of H.
      pylori from other parts of India, namely, Hyderabad, Mumbai and Lucknow. This
      finding supports the need for rigorous susceptibility testing as a guide to
      empirical treatment and more generally, to define the resistance patterns of H.
      pylori in particular geographical areas.

PMID- 15963081
TI  - Omeprazole delays gastric emptying in healthy volunteers: an effect prevented by
      tegaserod.
AB  - BACKGROUND: Proton-pump inhibitors effectively suppress stomach acidity. They are
      widely used for treating gastro-oesophageal reflux disease and related
      conditions. While generally safe, omeprazole and other proton-pump inhibitors can
      delay gastric emptying. AIM: To test the hypothesis that tegaserod can normalize
      or prevent omeprazole-induced delay in gastric emptying. METHODS: This was a
      randomized, double-blind, placebo-controlled, parallel group study in 40 healthy
      male volunteers. After informed consent and screening, qualified volunteers were
      treated with unblinded omeprazole 20 mg b.d. and either blinded tegaserod 6 mg
      t.d.s. (active treatment group) or placebo-matching tegaserod t.d.s. (control
      group) for 14 days. Gastric emptying was assessed before and after treatment,
      using a scintigraphy method. RESULTS: Omeprazole monotherapy significantly
      delayed gastric emptying expressed by duration of lag-phase (P < 0.007), time to
      gastric half-emptying (P < 0.003), and gastric retention of the meal at 60 (P <
      0.002) and 120 min (P < 0.04) after its ingestion. Tegaserod taken together with
      omeprazole effectively prevented development of the above effects. Combined
      treatment was safe and well tolerated. CONCLUSION: Concomitant administration of
      tegaserod 6 mg t.d.s. prevented development of the delayed gastric emptying
      induced by omeprazole monotherapy.

PMID- 15963082
TI  - Effect of concomitant dosing of famotidine with lansoprazole on gastric acid
      secretion in relation to CYP2C19 genotype status.
AB  - BACKGROUND: Famotidine increases Helicobacter pylori-eradication rates by a
      triple lansoprazole/amoxicillin/clarithromycin therapy in patients with the rapid
      extensive metabolizer genotype of CYP2C19. AIM: To determine the effect of
      famotidine on the gastric acid inhibition by lansoprazole in relation to CYP2C19
      genotypes. METHODS: Twenty healthy volunteers with different CYP2C19 genotypes-
      consisting of six rapid extensive metabolizers, nine intermediate metabolizers
      and five poor metabolizers--underwent three 7-day courses with placebo,
      lansoprazole 30 mg twice daily, and lansoprazole 30 mg twice plus famotidine 20
      mg twice daily. Lansoprazole was dosed after breakfast and dinner. Famotidine was
      dosed after lunch and at bedtime. Intragastric pH monitoring was performed for 24
      h on day 7 of each course. RESULTS: With placebo, no difference was observed in
      intragastric pH profiles among the three CYP2C19 genotype groups. With
      lansoprazole 30 mg twice daily, the median of 24-h intragastric pH in poor
      metabolizers (6.1) was significantly higher than those of rapid extensive
      metabolizers (4.5) and intermediate metabolizers (5.0), respectively (P = 0.0176
      and 0.0388), whereas with lansoprazole 30 mg twice and famotidine 20 mg twice
      daily, the medians were 5.4, 5.7, and 6.1, respectively (not significant).
      CONCLUSION: Acid inhibition by lansoprazole was influenced by CYP2C19 genotype
      status. This influence was offset by the concomitant use of famotidine.

PMID- 15963083
TI  - South Asian origin as a risk factor for GERD.

PMID- 15963084
TI  - Long-term follow-up of Helicobacter pylori eradication therapy in Vietnam:
      reinfection and clinical outcome.

PMID- 15963085
TI  - Polyethylene glycol for constipation: author's reply.

PMID- 15963086
TI  - Personalized drug therapy; the genome, the chip and the physician.

PMID- 15963088
TI  - Clinical pharmacology of DP-b99 in healthy volunteers: first administration to
      humans.
AB  - AIMS: To investigate the safety, tolerability and pharmacokinetics of DP-b99 in
      healthy volunteers. DP-b99 is a newly developed lipophilic, cell permeable
      derivative of BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid),
      which selectively modulates the distribution of metal ions in hydrophobic milieu,
      and is in clinical development as a neuroprotectant for cerebral ischaemic
      stroke. To our knowledge no BAPTA derivative has ever been administered to man.
      Here we report the first human administration of DP-b99 in a phase I, two-part,
      double-blind, randomized placebo controlled study, with single IV doses of 0.003
      1.0 mg kg(-1) day(-1) DP-b99 (part 1) or multiple ascending doses of 0.03-1.0 mg
      kg(-1) day(-1) DP-b99 over 4 days (part 2). METHODS: A double-blind, dose
      escalating tolerability study of DP-b99 in normal (young - aged between 18 and 40
      years and elderly - aged between 65 and 85 years) healthy adult male volunteers
      was conducted. Part 1 of the study investigated single administration of
      ascending intravenous doses, and part 2 examined the effects of ascending doses
      given repeatedly over 4 days. Twenty-four young volunteers in part 1 received
      single dose administrations and 26 young volunteers in part 2 received repeated
      ascending dose administrations of either intravenous DP-b99 or placebo.
      Subsequently, 10 elderly volunteers received repeated intravenous DP-b99 (1 mg
      kg(-1)) or placebo in part 2 over 4 days. Adverse events were identified by
      either subject self reporting or based upon laboratory parameters (blood
      chemistry, complete blood cell count, prothrombin time (PT), activated partial
      thromboplastin (PTT), physical examination, vital signs (blood pressure, pulse
      rate, respiratory rate, body temperature) and urinalysis. A comprehensive set of
      cardiovascular parameters was assessed as well (blood pressure, 12 lead-ECG
      recordings and continuous bedside cardiac monitoring for 6 h on day 1). RESULTS:
      The administration of DP-b99 up to the highest dose of 1.0 mg kg(-1) was well
      tolerated and had an acceptable safety profile up to the highest dose of 1.0 mg
      kg(-1) tested in both study parts. No serious or severe adverse events were
      encountered. Eight mild to moderate adverse events were observed in six of the
      seven young subjects treated with four repeated doses of 1.0 mg kg(-1), with
      reversible phlebitis being the most frequently reported adverse event. The drug
      was tolerated better at the injection site by the elderly group compared with the
      younger subjects. No adverse effects were observed in cardiovascular parameters
      sensitive to trans-membranous calcium concentrations. The pharmacokinetic
      parameters were derived by noncompartmental analysis. On day 1 following
      administration of 1 mg kg(-1) the mean half-life of DP-b99 in young volunteers
      was 3.47 +/- 0.90 h and in the elderly was 2.11 +/- 0.09 h. On day 4 following
      the same administration of DP-b99 the mean half-life was 4.36 +/- 1.49 and 2.10
      +/- 1.14 h in the young and elderly, respectively. There was higher systemic
      exposure in the elderly, for example C(max), had a mean 1.6-fold higher exposure
      on day 1 (95% CI Lower 0.90, Upper 2.74) and 2.5-fold on day 4 (95%CI 1.70,
      3.68). This increase is in line with the presumed central role of hepatic blood
      flow in the elimination of DP-b99. No accumulation was observed after repeated
      dosing with 1 mg kg(-1) (mean accumulation calculated by AUC(0, 24 h) (day 4) :
      AUC(0, 24 h) (day 1) and was observed to be between 0.9 and 1.3 (young, elderly).
      CONCLUSIONS: This study suggests that DP-b99 is well tolerated in healthy young
      and elderly volunteers within the dose range evaluated. Studies to investigate
      further the efficacy of the compound are in progress.

PMID- 15963089
TI  - Investigation of the effects of physiological and vasodilation-induced autonomic
      activation on the QTc Interval in healthy male subjects.
AB  - AIMS: Drug-induced prolongation of the QTc interval is an important marker for
      potential proarrhythmic action. Prolongation of the QTc interval results from
      alteration of the ionic currents that regulate cardiac repolarisation. Such
      effects may result from direct drug action or alternatively they could also occur
      indirectly by drug-induced modulation of autonomic tone, which is known to
      regulate cardiac repolarization. This study examined the effects of physiological
      and drug-induced autonomic activation on heart rate, QT and QTc intervals.
      METHODS: We studied 29 healthy male subjects aged 18-30 years.
      Electrocardiographs were recorded before and during autonomic activation induced
      by mental activation, standing, exercise and glyceryl trinitrate (GTN) (0.5 mg
      sublingual)-induced vasodilation in the presence and absence of beta-blockade
      (atenolol 100 mg daily for 4 days). QT intervals were measured manually by
      electronic callipers and corrected using the Fridericia formula. RESULTS: Heart
      rates were significantly increased during mental arithmetic, standing, exercise
      and GTN and this effect was significantly attenuated by atenolol, except for
      mental activation. QTc intervals were significantly reduced on standing and
      exercise and this was significantly attenuated by atenolol during exercise. In
      contrast, GTN increased QTc intervals (Delta = 5.7 ms, confidence interval +/-
      3.2 ms, P < 0.005) and this was not attenuated by atenolol. CONCLUSIONS:
      Alteration in QTc intervals may result from physiological manoeuvres and
      vasodilation, interventions known to induce autonomic activation. We suggest that
      QTc prolongation due to GTN is indirectly mediated and unlikely to carry any
      proarrhythmic effect. Understanding whether drug-induced QTc prolongation is
      directly or indirectly mediated may be important to determine any potential
      proarrhythmic risk.

PMID- 15963090
TI  - Levocetirizine has a longer duration of action on improving total nasal symptoms
      score than fexofenadine after single administration.
AB  - AIMS: To compare the onset and duration of action of the new antihistamine
      levocetirizine with that of the second-generation antihistamine fexofenadine
      using the Vienna Challenge Chamber (VCC). The latter is an environment where
      subjects can be exposed to specific aeroallergens in controlled and reproducible
      conditions allowing for precise comparisons of anti-allergic drugs. METHODS:
      Ninety-four subjects received a single dose of levocetirizine 5 mg, fexofenadine
      120 mg or placebo in a random order using a three-way cross-over design. On day
      1, subjects were exposed to grass pollens (1500 grains/m(3)) in the VCC over a
      period of 4 h. Treatment was given 2 h after the start of challenge. On day 2, 22
      h after drug intake, subjects were again exposed to pollens for 6 h. Specified
      symptoms were assessed by the subjects every 15 min using 5-point scales. The
      main efficacy parameter was the change from baseline in the Major Symptom Complex
      Score (MSCS = sum of rhinorrhea, sneezing, itchy nose and eyes). RESULTS:
      Baseline characteristics, including symptoms scores, were similar in the three
      study groups. During the first 2 h after drug intake both antihistamines achieved
      clinically relevant and significant (P < 0.001) improvements in symptom scores.
      Twenty-two to 24 h after drug intake, mean (SEM) MSCS reductions were: 1.9 (0.3)
      after placebo (baseline of 9.7), 3.8 (0.3) after fexofenadine (baseline of 9.9),
      and 5.1 (0.3) after levocetirizine (baseline of 9.8). Levocetirizine was
      significantly (P < 0.001) more effective than fexofenadine with a score
      difference of 1.3 (95% CI 0.7, 1.9). This was maintained until the end of the
      study (up to 28 h). CONCLUSIONS: A rapid onset of action in alleviating seasonal
      allergic rhinitis (SAR) symptoms of subjects exposed to grass pollens in the VCC
      was observed after levocetirizine and fexofenadine. Levocetirizine was more
      effective than fexofenadine at and later than 22 h after drug intake, an
      indication of the longer-duration of action of levocetirizine.

PMID- 15963091
TI  - Pharmacokinetic evidence for the induction of lopinavir metabolism by efavirenz.
AB  - AIMS: The influence of efavirenz on lopinavir pharmacokinetics was investigated
      using a population approach. METHODS: Forty-five HIV patients treated with
      lopinavir/ritonavir plus efavirenz (A) and 24 patients treated with
      lopinavir/ritonavir plus nucleoside/nucleotide reverse transcriptase inhibitors
      (B) were studied. RESULTS: A relationship (P < 0.01) was established between the
      elimination rate constant of lopinavir (k(10)) and treatment with efavirenz. Mean
      k(10) was higher in group A than in group B (0.3838 vs 0.2810 h(-1)) (P < 0.001,
      95% confidence interval for difference between means 0.1004, 0.1052).
      CONCLUSIONS: These results suggest that lopinavir metabolism is induced by
      efavirenz.

PMID- 15963092
TI  - Population pharmacokinetics of imatinib mesylate in patients with chronic-phase
      chronic myeloid leukaemia: results of a phase III study.
AB  - AIMS: This study was designed to investigate the biochemical and physiological
      covariates or comedications that affect the pharmacokinetics of imatinib mesylate
      in patients with chronic-phase chronic myeloid leukaemia (CP CML). METHODS:
      Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once
      daily during a phase III trial of imatinib vs interferon-alfa plus cytarabine for
      the treatment of newly diagnosed CP CML. Covariates included age, weight, sex,
      ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver
      function, and creatinine concentration. Blood samples for imatinib analysis were
      taken on treatment days 1 and 29. Nonlinear mixed effects modelling was used for
      the population pharmacokinetic analysis. RESULTS: Population mean estimates (95%
      confidence interval) at day 1 for apparent clearance (CL) and apparent volume of
      distribution (V) of imatinib were 14 (13-15) l h(-1) and 252 (237-267) l,
      respectively. Modelling suggested that CL decreased by 4 (3-5) l h(-1) from day 1
      to day 29, whereas V remained unchanged. Interindividual variability in CL and V
      was 32% and 31%, respectively. Weight, Hb, and WBC count demonstrated small
      effects on CL and V. Doubling body weight or Hb or halving the WBC count was
      associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60%
      and 5% increase in V, respectively. Comedications showed no clear effects on
      imatinib CL. CONCLUSIONS: Population covariates and coadministered drugs
      minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.

PMID- 15963093
TI  - Dexamethasone as a probe for vinorelbine clearance.
AB  - AIM: To assess the value of using dexamethasone as an in vivo probe for
      predicting vinorelbine clearance (CL). METHODS: A population approach
      (implemented with NONMEM) was used to analyse blood vinorelbine pharmacokinetic
      data from 20 patients who received a 20-min intravenous infusion of vinorelbine
      (from 20 to 30 mg m(-2)). Selected patient clinical data as well as known
      functional single CYP3A5 and ABCB1 genotype were also tested as covariates.
      RESULTS: The best covariate model (with +/- 95% confidence intervals) was based
      on dexamethasone plasma clearance (DPC) and alkaline phosphatase (ALP):
      vinorelbine blood CL (l h(-1)) = 39.8(+/- 4.0) x (DPC/13.2)(0.524(+/-0.322)) x
      (ALP/137)(-0.198(+/-0.158)). Interindividual variability in vinorelbine CL
      decreased from 29.7% (model without covariate) to 14.7% when including DPC and
      ALP. Vinorelbine CL was not correlated with body surface area (BSA) or associated
      with CYP3A5 and ABCB1 genotype. CONCLUSIONS: These results indicate that
      individualization of vinorelbine dose would be improved by using dexamethasone
      clearance rather than BSA. Dexamethasone merits further evaluation as a probe of
      CYP3A metabolism.

PMID- 15963094
TI  - Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract.
AB  - AIM: The aim of this study was to quantify the mRNA expression of three
      cytochromes P450 (CYP) and P-glycoprotein (P-gp) in the human gastrointestinal
      (GI) tract. METHOD: Biopsies were obtained from gastric, duodenal, colonic and
      rectal mucosa during routine gastro-colonoscopy in 27 patients. The biopsies were
      snap-frozen in liquid nitrogen. Real-time reverse transcriptase-polymerase chain
      reaction (RT-PCR) was used for the quantitative analyses of mRNA expressed by the
      CYP2E1, CYP3A4 and CYP3A5 genes, and the MDR1 gene coding for P-gp protein. The
      mRNA expression of b-actin was used as an internal standard for comparisons
      between samples. RESULTS: All CYP genes were expressed at all locations
      throughout the GI tract, although all showed substantial interindividual
      variation. CYP2E1 had the highest expression at all locations (P < 0.05 to P <
      0.0001), except in the right colon. CYP3A4 and CYP3A5 had their highest mRNA
      expression in the duodenum (P < 0.001 and P < 0.000 001, respectively) and CYP2E1
      in the stomach (P < 0.01). MDR1 mRNA concentrations increased along the GI tract
      with the highest expression being in the left colon (P < 0.000001). CONCLUSION:
      Multiple sampling within the same individual enabled us to study the
      intraindividual variation in expression of CYP and MDR1 genes along the GI tract.
      We find that CYP2E1 mRNA expression is higher than that of the other CYPs. CYP3A
      expression is highest in the duodenum and that of MDR1 increases from stomach and
      duodenum to colon.

PMID- 15963095
TI  - Enantioselective disposition of lansoprazole in relation to CYP2C19 genotypes in
      the presence of fluvoxamine.
AB  - AIMS: Lansoprazole is affected by polymorphism of CYP2C19. The aim of this study
      was to examine the effects of fluvoxamine, a CYP2C19 inhibitor, on the
      pharmacokinetics of each lansoprazole enantiomer among three different CYP2C19
      genotype groups. METHODS: Eighteen healthy subjects, of whom six each were
      homozygous extensive metabolizers (homEMs), heterozygous extensive metabolizers
      (hetEMs), or poor metabolizers (PMs) for CYP2C19, participated in the study. Each
      subject received either placebo or fluvoxamine, 25 mg twice daily for 6 days,
      then a single oral dose of 60 mg of racemic lansoprazole. The plasma
      concentrations of lansoprazole enantiomers and lansoprazole sulphone were
      subsequently measured for 24 h post lansoprazole administration using liquid
      chromatography. RESULTS: In the homEMs and hetEMs, fluvoxamine significantly
      increased the AUC(0, infinity) and C(max) and prolonged the elimination half-life
      of both (R)- and (S)-lansoprazole, whereas in the PMs, the only statistically
      significant effect of fluvoxamine was on the AUC(0, infinity) for (R)
      lansoprazole. The mean fluvoxamine-mediated percent increase in the AUC(0,
      infinity) of (R)-lansoprazole in the homEMs compared with the PMs was significant
      (P = 0.0117); however, C(max) did not differ among the three CYP2C19 genotypes.
      On the other hand, fluvoxamine induced a significant percent increase in both the
      AUC(0, infinity) and C(max) for (S)-lansoprazole in the homEMs compared with the
      hetEMs (P = 0.0007 and P = 0.0125, respectively) as well as compared with the PMs
      (P < 0.0001 for each parameter). The mean R : S ratio for AUC(0, infinity) of
      lansoprazole in the homEMs was significantly different between the placebo and
      the fluvoxamine treatment groups (12.7 (9.1, 16.8) vs 6.4 (5.4, 7.4),
      respectively, P < 0.0001), though not in the PMs (5.5 (4.3, 6.7) vs 5.9 (5.3,
      6.5), respectively). CONCLUSIONS: The magnitude of the contribution of CYP2C19 to
      the metabolism of (S)-lansoprazole is much greater compared with that of the (R)
      enantiomer. In extensive metabolizers, hepatic CYP2C19 plays an important role in
      the absorption and elimination of lansoprazole, particularly the (S)-enantiomer.

PMID- 15963096
TI  - The role of CYP2C and CYP3A in the disposition of 3-keto-desogestrel after
      administration of desogestrel.
AB  - AIMS: Our objective was to study in vivo the role of CYP2C and CYP3A4 in the
      disposition of 3-keto-desogestrel after administration of desogestrel, by using
      the selective inhibitors fluconazole (CYP2C) and itraconazole (CYP3A4). METHODS:
      This study had a three-way crossover design and included 12 healthy females, the
      data from 11 of whom were analyzed. In the first (control) phase all subjects
      received a single 150 microg oral dose of desogestrel alone. In the second and
      third phases subjects received a 4 day pretreatment with either 200 mg
      fluconazole or 200 mg itraconazole once daily in a randomized balanced order.
      Desogestrel was given 1 h after the last dose of the CYP inhibitor. Plasma 3-keto
      desogestrel concentrations were determined for up to 72 h post dose. RESULTS:
      Pretreatment with itraconazole for 4 days significantly increased the area under
      the plasma concentration-time curve (AUC) of 3-keto-desogestrel by 72.4% (95%
      confidence interval on the difference 12%, 133%; P = 0.024) compared with the
      control phase, whereas fluconazole pretreatment had no significant effect (95% CI
      on the difference -42%, 34%). Neither enzyme inhibitor affected significantly the
      maximum concentration (95% CI on the difference 14%, 124% for itraconazole and 
      23%, 40% for fluconazole) or elimination half-life (95% CI on the difference 
      42%, 120% for itraconazole and -24%, 61% for fluconazole) of 3-keto-desogestrel.
      CONCLUSIONS: According to the present study, the biotransformation of desogestrel
      to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as
      suggested earlier. However, the further metabolism of 3-keto-desogestrel seems to
      be catalyzed by CYP3A4.

PMID- 15963097
TI  - Risk of cholestatic liver disease associated with flucloxacillin and
      flucloxacillin prescribing habits in the UK: cohort study using data from the UK
      General Practice Research Database.
AB  - AIMS: To provide additional quantification of the risk of flucloxacillin-related
      liver disease and to describe time trends in flucloxacillin prescribing in the
      UK. METHODS: This was a cohort study using data from the UK General Practice
      Research Database. We identified patients with a first-time prescription for
      flucloxacillin or, for comparison, oxytetracycline from 1992 to 2002 and cases
      who developed clinically documented cholestatic liver disease of uncertain origin
      after first-time use of these drugs. We also determined the annual frequency of
      first-time use of flucloxacillin from 1991 to 2000. RESULTS: We identified 283
      097 and 131 189 first-time users of flucloxacillin and oxytetracycline,
      respectively. The risk of cholestatic liver disease per 100 000 first-time users
      was 8.5 (95% CI 5.4, 12.6) in the 1-45 days and 1.8 (95% CI 0.6, 4.1) in the 46
      90 days after starting flucloxacillin, and 0.8 (95% CI 0.02, 4.3) in the 1-45
      days after starting oxytetracycline. The frequency of first-time use of
      flucloxacillin remained stable between 1991 and 2000. CONCLUSIONS: Flucloxacillin
      is now established as an important cause of cholestatic liver disease. Warnings
      about the risk have not had an impact on prescribing practices in the UK, where
      it remains the predominantly prescribed antistaphylococcal oral antibiotic. This
      situation in the UK is in sharp contrast to regulatory actions and changes in
      prescribing habits in Australia after identification of the risk of cholestasis
      associated with flucloxacillin, and to the predominant use of the alternative
      drug dicloxacillin in the USA.

PMID- 15963098
TI  - Suboptimal choices and dosing of statins at start of therapy.
AB  - AIM: To assess dosing and determinants of the choice of statins among starters of
      statins. METHODS: Data were obtained from the PHARMO database comprising pharmacy
      and linked hospital discharge records of approximately 300 000 subjects in the
      Netherlands. All new users of statins in 1998 were selected. Patient
      characteristics and drug regimens were compared between starters of different
      statins. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using
      polytomous logistic regression modelling, using the start of simvastatin therapy
      as reference category. RESULTS: In 1998, 1738 patients started using simvastatin
      (41.1%), pravastatin (23.1%), fluvastatin (11.9%), atorvastatin (22.8%) or
      cerivastatin (1.0%). Compared with starters with simvastatin [mean dose 1.02 +/-
      0.39 defined daily doses (DDDs)], starters with pravastatin (1.27 +/- 0.56 DDDs)
      and atorvastatin (1.43 +/- 0.59 DDDs) received higher doses (P < 0.001), whereas
      users of fluvastatin (0.78 +/- 0.37 DDDs) and cerivastatin (0.81 +/- 0.30 DDDs)
      received lower doses (P < 0.001). Patients already using CYP3A4 inhibitors more
      frequently received fluvastatin (OR = 1.80; 95% CI 1.11, 2.94), metabolized by
      non-CYP3A4 pathways, and atorvastatin (OR = 1.62; 95% CI 1.06, 2.47), which is
      metabolized by CYP3A4, than simvastatin. Statin doses were not adjusted when
      prescribed to patients using CYP3A4 inhibitors. CONCLUSIONS: Many patients
      starting statin therapy did not receive a statin of first choice. The
      coadministration of potentially interacting drugs may have led to a change in
      statin choice, but not in dosage lowering. These findings suggest that the
      quality of statin therapy could be improved.

PMID- 15963099
TI  - Queen Mary Utilization of Antihypertensive Drugs Study: use of antihypertensive
      drug classes in the hypertension clinic 1996-2004.
AB  - BACKGROUND: Utilization of antihypertensive drugs in the hypertension outpatient
      clinic is surveyed periodically in the Queen Mary Utilization of Antihypertensive
      Drugs Study (QUADS). METHODS: Two hundred and fifty-one patients (123 men, 128
      women) were interviewed in April to December 1996, 439 patients (232 men, 207
      women) in January to December 99 and 228 patients (109 men, 119 women) in April
      to May 2004. Their case notes were reviewed. RESULTS: The percentages of patients
      receiving no drug (lifestyle modification), one, two, three and over three drugs
      were 7%, 48%, 36%, 7%, 3%, respectively, in 1996; 14%, 34%, 36%, 13% and 1%,
      respectively, in 1999; and 3%, 30%, 40%, 22% and 6%, respectively, in 2004. The
      number of drugs correlated with age and overweight. In 1996, 51% patients
      received calcium channel blockers (CCB); 46% beta-blockers (BB); 32% angiotensin
      converting enzyme inhibitors (ACEI); 15% thiazide diuretics; 5% alpha-blockers;
      and 0% angiotensin receptor blockers (ARB). In 1999, the respective figures were
      52% CCB, 49% BB, 24% ACEI, 22% thiazide diuretics, 4%alpha-blockers and 2% ARB.
      In 2004, the respective figures were 65% CCB, 64% BB, 33% ACEI, 24% thiazide
      diuretics, 4% alpha-blockers and 7% ARB. Fewer patients on BBs reported side
      effects. Only 11% were on alpha statin and 9% on aspirin. Blood pressure on
      treatment was 147 +/- 21/84 +/- 11 mmHg in 1999 and 144 +/- 21/82 +/- 11 mmHg in
      2004. CONCLUSIONS: Increasingly, multiple drugs were used for blood pressure
      control. Blood pressure control needs improvement, especially in diabetics. CCBs
      and BBs were consistently popular. Thiazide diuretics, ARBs, statins and aspirin
      were underused, despite favourable clinical trial evidence.

PMID- 15963100
TI  - Deep vein thrombosis and pulmonary embolism reported in the Prescription Event
      Monitoring Study of Yasmin.
AB  - AIM: To evaluate cases of deep vein thrombosis (DVT) and pulmonary embolism (PE)
      reported in a prescription event monitoring study of Yasmin, an oral
      contraceptive. METHODS: Reports of DVT/PE and events suggestive of DVT/PE were
      followed up by questionnaire. RESULTS: Thirteen cases (DVT five; PE eight), each
      with possible risk factor(s), were identified in 15 645 females using Yasmin.
      Applying complete case analysis, the crude incidence rate was 13.7 cases per 10
      000 woman-years (95% confidence interval 7.3, 23.4). CONCLUSIONS: Yasmin is
      associated with venous thromboembolism. An incidence rate has been calculated,
      but this may be subject to bias and should be interpreted with caution.

PMID- 15963101
TI  - Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on
      medication with sulphonylurea hypoglycaemic agents.
AB  - AIMS: The genetically polymorphic cytochrome P450 (CYP) enzyme CYP2C9 metabolizes
      most sulphonylurea oral hypoglycaemic agents. The aim of this study was to test
      the hypothesis that individuals with genotypes predicting low CYP2C9 activity may
      be at a higher risk of severe drug-associated hypoglycaemia. METHODS: In a case
      control study, 20 diabetic patients admitted to the emergency department with
      severe hypoglycaemia during sulphonylurea drug treatment were compared with a
      control group of 337 patients with type 2 diabetes but without a history of
      severe hypoglycaemia. A large sample of 1988 healthy Caucasian subjects served as
      a second control group. RESULTS: The CYP2C9 genotypes *3/*3 and *2/*3 that are
      predictive of low enzyme activity were more common in the hypoglycaemic group
      than in the comparison groups (10%vs <2%, respectively: odds ratio 5.2; 95%
      confidence interval 1.01, 27). Furthermore, the diabetic patient group with
      severe hypoglycaemia exhibited lower body mass indexes, higher rates of renal
      failure, were older compared with the diabetic group without severe
      hypoglycaemia, and were being treated with higher doses of glibenclamide.
      CONCLUSIONS: These findings suggest that among other factors, individuals with
      genetically determined low CYP2C9 activity are at an increased risk of
      sulphonylurea-associated severe hypoglycaemia. Thus, genotyping might be a tool
      for the better prediction of adverse effects caused by oral hypoglycaemic agents.

PMID- 15963102
TI  - Bosentan decreases the plasma concentration of sildenafil when coprescribed in
      pulmonary hypertension.
AB  - AIMS: To determine whether bosentan decreases the plasma concentration of
      sildenafil in patients with pulmonary arterial hypertension. METHODS: Ten
      patients (aged 39-77 years) with pulmonary arterial hypertension in WHO
      functional class III received bosentan 62.5 mg twice daily for 1 month, then 125
      mg twice daily for a second month. Sildenafil 100 mg was given as a single dose
      before starting bosentan (visit 1) and at the end of each month of bosentan
      treatment (visits 2 and 3). Sildenafil and its primary metabolite,
      desmethylsildenafil, were measured in plasma at 0 h and 0.25, 0.5, 1, 1.5, 2, 3,
      4, 6, 8, 10, 12, 18 and 24 h using liquid chromatography-tandem mass
      spectrometry. Statistical analysis was by repeated measures anova, using log
      transformed data where appropriate. RESULTS: Treatment with bosentan 62.5 mg
      twice daily for 4 weeks was associated with a two-fold increase in sildenafil
      clearance/F and a 50% decrease in the AUC (P < 0.001). Increasing the dose of
      bosentan to 125 mg twice daily led to a further increase in sildenafil oral
      clearance and decrease in the AUC (P < 0.001 vs. 62.5 mg bosentan). The ratio of
      AUC on bosentan treatment relative to that of visit 1 was 0.47 [95% confidence
      interval (CI) 0.36, 0.61] for visit 2 and 0.31 (95% CI 0.23, 0.41) for visit 3 (P
      < 0.001). Sildenafil C(max) fell from 759 ng ml(-1) on visit 1 to 333 ng ml(-1)
      on visit 3 (P < 0.01) and there was a significant decrease in the plasma half
      life of sildenafil on the higher bosentan dose (P < 0.05). The AUC and plasma
      half-life of desmethylsildenafil was also decreased by bosentan in a dose
      dependent manner (P < 0.01). CONCLUSIONS: Bosentan significantly decreases the
      plasma concentration of sildenafil when coadministered to patients with pulmonary
      hypertension.

PMID- 15963106
TI  - Inadvertent intrathecal administration of rifampicin.

PMID- 15963107
TI  - Beyond marketing: the real value of robotic radical prostatectomy.

PMID- 15963108
TI  - Prolonging survival in prostate cancer: chemotherapy will have an important role.

PMID- 15963109
TI  - alpha-acylmethyl co-enzyme A racemase: a tumour marker for the 21st century?

PMID- 15963110
TI  - The 'flare' phenomenon: should we be concerned?

PMID- 15963111
TI  - Molecular staging of bladder cancer.
AB  - Attempts are being made in many laboratories to find new biomarkers for and new
      methods of molecular staging of bladder cancer. At the forefront of this are the
      authors from Los Angeles who have contributed the first of four mini-reviews in
      this section. Other mini-reviews examine the role of hand-assisted laparoscopy in
      urology, a contribution to the sometimes heated argument about whether
      laparoscopy should be 'pure' or hand-assisted: in addition, two mini-reviews
      describe the role of photodynamic diagnosis in managing superficial bladder
      cancer, and the contribution of non-surgical factors to the success of
      hypospadias repair.

PMID- 15963112
TI  - The role of hand-assisted laparoscopy in urology: a critical appraisal.

PMID- 15963113
TI  - The role of photodynamic diagnosis in the contemporary management of superficial
      bladder cancer.

PMID- 15963114
TI  - Nonsurgical factors in the success of hypospadias repair.

PMID- 15963115
TI  - Racial differences in serum prostate-specific antigen (PSA) doubling time,
      histopathological variables and long-term PSA recurrence between African-American
      and white American men undergoing radical prostatectomy for clinically localized
      prostate cancer.
AB  - OBJECTIVE: To determine if there are significant differences in biochemical
      characteristics, biopsy variables, histopathological data, and rates of prostate
      specific antigen (PSA) recurrence between African-American (AA) and white
      American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as
      likely to die from prostate cancer than their white counterparts. PATIENTS AND
      METHODS: We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and
      were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score,
      clinical stage, pathological stage, and PSA recurrence data were available for
      the cohort. The chi-square test of proportions and t-tests were used to assess
      basic associations with race, and log-rank tests and Cox regression models for
      time to PSA recurrence. Forward stepwise variable selection was used to assess
      the effect on the risk of PSA recurrence for race, adjusted by the other
      variables added one at a time. RESULTS: The AA men had higher baseline PSA
      levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the
      biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had
      a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years.
      However, race was not an independent predictor of PSA recurrence (P = 0.225).
      Important predictors for PSA recurrence in a multivariable model were biopsy
      HGPIN (P < 0.014), unilateral vs bilateral cancer (P < 0.006), pathology Gleason
      score and positive margin status (both P < 0.001). CONCLUSIONS: This study
      indicates that while there are racial differences in baseline serum PSA and
      incidence of HGPIN, race is not an independent risk factor for PSA recurrence.
      Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN
      and margin positivity are independently associated with PSA recurrence. The PSA
      doubling time after recurrence may also be important, leading to the increased
      mortality of AA men with prostate cancer.

PMID- 15963116
TI  - Installation of telerobotic surgery and initial experience with telerobotic
      radical prostatectomy.
AB  - OBJECTIVE: To assess the ability of untrained laparoscopic surgeons to learn and
      implement laparoscopic telerobotic radical prostatectomy (TRP) using the daVinci
      Surgical System (Intuitive Surgical, CA), and assess the education, safety and
      efficacy issues when instituting this system. PATIENTS AND METHODS: Between
      December 2003 and October 2004, 122 consecutive TRPs were performed by two
      surgeons for clinically localized prostate cancer. The individual robotic surgeon
      was assisted at the bedside by another surgeon. The TRP was performed robotically
      by the surgeon at the remote console unit. Perioperative data and pathological
      results were recorded. The two surgeons spent 1 week in a skills laboratory using
      a porcine model of laparoscopic TRP, and then cadaveric robotic prostatectomy.
      The first six cases were mentored by an experienced telerobotic surgeon. RESULTS:
      The TRP was conducted by two surgeons with no previous laparoscopic experience.
      There were no conversions to open surgery. Assessing the complications,
      postoperative continence, operating time and transfusion rates showed equivalent
      efficacy and safety to open and pure laparoscopic methods. CONCLUSION: TRP
      represents a novel computer-based surgical approach to prostate cancer, which
      offers the benefits of minimally invasive surgery without the extensive
      experience associated with the laparoscopic method. It remains to be seen whether
      the robotic approach can deliver better outcomes in continence and potency over
      time.

PMID- 15963117
TI  - Robot-assisted vs pure laparoscopic radical prostatectomy: are there any
      differences?
AB  - OBJECTIVE: To compare our experience of pure laparoscopic radical prostatectomy
      (LRP) with robot-assisted radical prostatectomy (RAP). PATIENTS AND METHODS: The
      two techniques were compared retrospectively in 100 patients with localized
      prostate cancer who had LRP or RAP (50 each). Both groups were similar in age,
      serum prostate-specific antigen level, Gleason score and clinical stage. Their
      charts were reviewed, collating intraoperative data and early functional outcome.
      RESULTS: The mean surgical time for LRP and RAP was 235 and 202 min (P > 0.05)
      and mean (95% confidence interval) blood loss 299 (40) and 206 (63) mL (P =
      0.014), with no transfusions in either group. The positive margin rate did not
      differ significantly (14% LRP and 12% RAP) and there was no biochemical
      recurrence in either group. Early functional outcomes were similar. CONCLUSIONS:
      Both LRP and RAP are technically demanding, but feasible, with the patient
      clearly benefiting. There were no major surgical differences between the
      techniques, but RAP is more costly.

PMID- 15963118
TI  - Radical prostatectomy versus high-dose rate brachytherapy for prostate cancer:
      effects on health-related quality of life.
AB  - OBJECTIVE: To examine the effects of different treatments on the health-related
      quality of life (HRQoL) of men with localized prostate cancer. PATIENTS AND
      METHODS: Between October 1997 and August 2002, 182 men diagnosed with prostate
      cancer (T1c to T3bN0M0) had radical prostatectomy (RP, 89) or (192)iridium high
      dose rate brachytherapy (HDR-BT, 93) with external beam radiotherapy, and were
      followed for > or = 6 months. A postal survey was sent in which HRQoL was
      assessed using the 36-item Short-Form Health Survey (SF-36) QoL questionnaire,
      and disease-specific QoL using the University of California Los Angeles Prostate
      Cancer Index (UCLA-PCI). RESULTS: Questionnaire responses were obtained from 151
      of 182 patients; there was no significant difference in SF-36 scale scores
      between men treated with RP or HDR-BT. In the UCLA-PCI, the HDR-BT group had
      better urinary function (P < 0.001) and sexual function scores (P= 0.043). Men
      treated with RP had better bowel bother scores (P = 0.027). In patients with > or
      = 2 years of follow-up, urinary function (P < 0.001) and sexual bother (P =
      0.029) were better for men treated with HDR-BT than for men treated with RP. Men
      treated with HDR-BT had significantly better urinary function (P = 0.009) and
      sexual bother (P = 0.013) even than 30 men treated with unilateral nerve-sparing
      RP. CONCLUSIONS: In terms of HRQoL, RP and HDR-BT did not differ, but HDR-BT
      resulted in better urinary and sexual function than RP. When planning treatment,
      QoL concerns, including mental health issues associated with prostate cancer,
      need to be addressed with the patients, as do the potential side-effects.

PMID- 15963119
TI  - Does neoadjuvant hormone therapy for early prostate cancer affect cognition?
      Results from a pilot study.
AB  - OBJECTIVE: To examine, in a prospective study, the influence that temporary
      reversible medical castration for localized prostate cancer has on cognition, by
      assessing whether temporary 3-5 month treatment with a luteinizing-hormone
      releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long
      term affect on cognitive function. PATIENTS, SUBJECTS AND METHODS: Thirty-two
      patients with localized prostate cancer had cognitive assessments at baseline
      (T1) before the start of drug treatment, at 3 months (T2) or on completing drug
      treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no
      prostate cancer (controls subjects) completed the cognitive tests at the same
      times. In addition, psychological functioning and quality of life were assessed
      at the same times, together with serum free and bound testosterone, beta
      oestradiol and sex hormone-binding globulin levels. RESULTS: There was a
      significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%)
      patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients
      (nine of 15) who had a change in performance declined on tasks of spatial memory
      and ability. At T3 there was significant cognitive decline in 11 (34%) patients
      and five (28%) control subjects (odds ratio 1.37, P = 0.631). CONCLUSION: This
      pilot study suggests that short-term LHRH therapy for early-stage prostate cancer
      has modest short-term consequences on men's cognitive functioning; a larger
      prospective study is warranted.

PMID- 15963120
TI  - Surgical treatment of stage pT3b renal cell carcinoma in solitary kidneys: a case
      series.
AB  - OBJECTIVE: To describe the surgical management of patients with renal cell
      carcinoma (RCC) in a solitary kidney (managed preferentially by nephron-sparing
      surgery, NSS, to avoid dialysis) and extending into the renal vein or inferior
      vena cava (T3b). PATIENTS AND METHODS: We identified 13 patients treated
      surgically between 1977 and 2002 for stage T3b RCC in a solitary kidney; their
      charts were reviewed to ascertain details of management, pathology and outcomes.
      RESULTS: NSS was successful in seven patients (four in situ and three
      extracorporeally). Five patients had radical nephrectomy (RN), four after failed
      NSS. The mean (sem) operative duration was longer for NSS, at 5.8 (0.7) h, than
      RN, at 3.3 (0.6) h. There was one death during surgery before nephrectomy, and
      eight other complications in six patients. At a median (range) follow-up of 24 (0
      204) months, eight patients had died, four from RCC (all having had NSS) at a
      median interval of 9.5 (7-16) months. Of the five patients alive at a median
      follow-up of 25 months, four had no identifiable disease, whilst one had systemic
      recurrence. CONCLUSIONS: NSS combined with venous tumour thrombectomy for
      treating T3b RCC involving a solitary kidney is feasible, albeit complicated.
      There was oncological success in a third of the patients. The treatment of these
      patients needs to be individualized, as alternatives to NSS (RN or observation)
      have obvious disadvantages.

PMID- 15963121
TI  - A description of radical nephrectomy practice and outcomes in England: 1995-2002.
AB  - OBJECTIVES: To describe national trends in the practice of radical nephrectomy
      (RN) in England between 1995 and 2002. METHODS: Data were extracted from the
      Hospital Episode Statistics database of the Department of Health in England
      between 1995/1996 and 2001/2002. Patients were included in the study if an
      International Classification of Diseases diagnosis code (ICD-10) for malignant
      neoplasm of the kidney, renal pelvis or ureter, and an operative procedure code
      (OPCS-4) describing total or partial excision of the kidney by either a
      laparoscopic or open approach, were present in any of the diagnosis or operative
      procedure fields. Overall, 17 308 patients were included. RESULTS: Patient age
      and the proportion who were men did not change over the study period. The
      proportion of patients admitted as an emergency decreased from 14.0% to 7.5% over
      this period (P < 0.001). The mean waiting duration increased by almost 6 days (P
      < 0.001) and length of stay by approximately 1 day, from 11.7 days in 1995 to
      10.8 days in 2001 (P < 0.001). In-hospital mortality decreased from 2% to 1.5% (P
      = 0.134). In-hospital mortality and length of stay were higher in older patients
      and in those admitted as an emergency. Women had a longer stay than men (11.5 vs
      11.1 days), but in-hospital mortality was higher in men (2.3% vs 1.6%). The
      national number of RNs per year increased by approximately 20%, from 2254 in 1995
      to 2671 in 2001. Over the same period the mean annual hospital volume of RN
      increased by approximately 40%, from 17 in 1995 to 24 in 2001. The annual number
      of laparoscopic RNs nationally increased from seven in 1995 to 84 in 2002.
      CONCLUSIONS: The annual number of RNs in England increased by almost a fifth and
      this was accompanied by an increase in annual hospital volume of about two
      fifths. There was a large proportional increase in the number of laparoscopic
      RNs. Emergency admission rates and length of stay decreased but this was not
      accompanied by a significant change in in-hospital mortality rate.

PMID- 15963122
TI  - The relationship between angiogenesis and cyclooxygenase-2 expression in prostate
      cancer.
AB  - OBJECTIVE: To test the hypothesis that angiogenesis in prostate cancer is
      associated with tumour invasion and metastasis, and that this is mediated through
      increased cyclooxygenase-2 (COX-2) expression. PATIENTS AND METHODS: Angiogenesis
      was assessed in 105 patients with either prostate cancer (79) or benign prostatic
      hyperplasia (BPH, 26) and these data correlated with levels of COX-2 expression
      in the same dataset. The mean microvessel density (MVD) was analysed as a marker
      of angiogenesis, using the endothelial antigen CD34 stained by
      immunohistochemistry. RESULTS: There was no difference in MVD in progressive
      tumour stages compared with BPH. There was a negative correlation between MVD and
      COX-2 expression, but the effect of increased COX-2 expression on MVD was not
      marked. CONCLUSION: These data suggest that COX-2 drives tumour spread in
      prostate cancer by means other than the promotion of angiogenesis.

PMID- 15963123
TI  - Testicular-sparing microsurgery for suspected testicular masses.
AB  - OBJECTIVE: To describe a microsurgical technique for removing suspected
      testicular masses with sparing of the testicular parenchyma, and to describe case
      studies. PATIENTS AND METHODS: Six men were referred with testicular lesions (3-6
      mm) detected on ultrasonography (US); in one, the lesion was palpable. US showed
      hypoechoic lesions and in two cases were mixed hypoechoic and anechoic. In these
      men, the testicular lesion was identified by US before surgery, giving three
      dimensional coordinates to facilitate intraoperative recognition. A traditional
      inguinal incision was used and the funiculus clamped subinguinally without
      opening the canal. The testicle was isolated after sectioning the gubernaculum
      testis. In a separate operative field, an equatorial incision of the albuginea
      was made in a plane orthogonal to the major axis of the testicle, sparing the
      subtunical vasa. The parenchymal lobuli were dislodged and the seminiferous
      tubules dissociated, the nodule identified and completely removed, together with
      approximately 1 mm of surrounding healthy tissue. This technique can also be used
      for microsurgical testicular sperm extraction (MicroTESE), to retrieve sperm in
      infertile men. RESULTS: In two infertile men MicroTESE was also performed.
      Histology revealed one case each of seminoma, Leydig-cell tumour, Leydig cell
      hyperplasia, atrophy, normality in the incidental forms, and complicated cysts of
      the albuginea. In the follow-up for infertility reasons, no scarring was
      observable on the tunica albuginea in the men who had conservative therapy. One
      year later the patient with seminoma was free of disease. CONCLUSIONS: The
      increasingly frequent detection of benign testicular lesions, particularly in
      infertile men, calls for a surgical approach that must be as conservative as
      possible for the testicular parenchyma. We think that microsurgery should be the
      first-line technique in small suspected testicular lesions in infertile men.

PMID- 15963124
TI  - Extracorporeal application of high-intensity focused ultrasound for prostatic
      tissue ablation.
AB  - OBJECTIVE: To investigate the efficacy and safety of extracorporeal prostatic
      tissue ablation using high-intensity focused ultrasound (HIFU) in vivo in
      animals, and in a clinical feasibility study in men, as this is an
      investigational minimally invasive treatment alternative for locally confined
      prostatic carcinoma, but may have significant side-effects. PATIENTS, MATERIALS
      AND METHODS: Ultrasound (1.04 MHz excitation frequency) was generated by an
      extracorporeal cylindrical piezo-ceramic element and focused by a paraboloidal
      reflector to a focal size of 32 x 4 mm. The focal distance and aperture diameter
      were both 100 mm. HIFU was applied extracorporeally at different intensities and
      pulse duration (up to 6 s) to 11 dog prostates in vivo (median intensity 1192
      W/cm2) and eight patients (median intensity 3278 W/cm2, range 2384-3576) under
      general anaesthesia. The lesions were assessed macroscopically and histologically
      after HIFU and any side-effects evaluated. RESULTS: Thermoablation was feasible
      in vivo and in all patients. Macroscopic analysis and histology showed sharply
      demarcated coagulative necrosis. Side-effects, including skin and rectal burns,
      occurred only after transvesical application in the in vivo study. There were no
      side-effects in patients after perineal application. CONCLUSION: Extracorporeal
      HIFU is technically feasible and induces sharply demarcated tissue damage in the
      prostate. From the early results of this phase 1 study, the perineal approach
      seems to be safe.

PMID- 15963125
TI  - Association of cigarette smoking, alcohol consumption and physical activity with
      lower urinary tract symptoms in older American men: findings from the third
      National Health And Nutrition Examination Survey.
AB  - OBJECTIVES: To examine the association of cigarette smoking, alcohol consumption
      and physical activity with lower urinary tract symptoms (LUTS) in older men.
      SUBJECTS AND METHODS: The study included 2797 men participating in the Third
      National Health and Nutrition Examination Survey (NHANES III), who were aged > or
      = 60 years. During an interview, LUTS, smoking history, alcohol consumption and
      physical activity were assessed. Cases comprised men with at least three of the
      symptoms of nocturia, hesitancy, weak stream and incomplete emptying. Men who had
      had prostate surgery unrelated to cancer were not included as cases. Controls
      were men with no symptoms or surgery. We adjusted for age and race in logistic
      regression models and used sampling weights to account for selection probability.
      RESULTS: Current cigarette smokers had no higher odds of LUTS than 'never'
      smokers, but former heavy smokers (> or = 50 pack-years) had a higher odds of
      LUTS than never smokers (odds ratio 2.01; 95% confidence interval 1.04-3.89). Men
      who drank alcohol daily had a lower chance of LUTS than non-drinkers (0.59; 0.37
      0.95; P trend, 0.07). All levels of moderate and vigorous activity were
      statistically significantly inversely associated with LUTS (P trend, 0.06),
      whereas men who reported no leisure-time physical activity had a greater odds of
      LUTS (2.06; 1.26-3.39). CONCLUSIONS: Moderate alcohol consumption and physical
      activity may be protective against LUTS. Current cigarette smoking was not
      consistently associated with the condition. The possible association in former
      smokers warrants further investigation.

PMID- 15963126
TI  - Relevance and variability of the severity of incontinence, and increased daytime
      and night-time voiding frequency, associated with quality of life in men with
      lower urinary tract symptoms.
AB  - OBJECTIVES: To estimate the distribution of the severity of urinary incontinence
      (UI) and daytime and night-time voiding in patients with lower urinary tract
      symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH); to estimate the
      proportion of 'subjectively relevant' symptoms within each severity category; to
      identify differences in quality of life (QoL) by degree of subjectively relevant
      daytime and night-time symptoms; and to identify differences in QoL in men with
      subjectively relevant UI or no UI. PATIENTS AND METHODS: Data from a group of 480
      men awaiting urological assessment for LUTS suggestive of BPH were collected by
      questionnaire shortly after referral from their general practitioner in 1997
      2000. The International Continence Society--Benign Prostatic Hyperplasia Index,
      Sandvik's Incontinence Severity Index, and the World Health Organization Quality
      of Life Survey--Abbreviated Version (WHOQoL-bref) were used to assess symptoms
      and QoL. RESULTS: There was a large heterogeneity of self-reported symptom
      severity and related bother in the three symptoms of UI, increased daytime
      voiding frequency and night-time voiding in these referred patients. The WHOQoL
      bref showed significant group differences of subjectively relevant symptoms.
      CONCLUSION: The perception of increased night and daytime frequency, as measured
      by symptom severity and bother, varied greatly. The severity of UI and its effect
      on men waiting for a urological assessment of LUTS suggestive of BPH also varied
      widely. In general, the symptoms and their impact were slight to moderate. The
      WHOQoL-bref could be used to differentiate among groups of subjectively relevant
      symptoms, and in so doing supported information generated by the bother question.

PMID- 15963127
TI  - The prevalence and correlates of urinary tract symptoms in Norwegian men: the
      HUNT study.
AB  - OBJECTIVES: To estimate the prevalence of lower urinary tract symptoms (LUTS) by
      severity (using the International Prostate Symptom Score, IPSS) in a population
      based study of men aged > or = 20 years, and to assess the association between
      putative risk factors and the presence of moderate to severe LUTS. SUBJECTS AND
      METHODS: Between 1995 and 1997, LUTS data were collected from 21 694 male
      residents aged > or = 20 years in Nord Trondelag County in Norway, using the
      IPSS; from the IPSS (score 0-35) LUTS was defined as a score of > or = 8,
      indicating moderate to severe symptoms. We estimated the prevalence of LUTS and
      used logistic regression analysis to study lifestyle and anthropometric factors,
      and comorbidity related to LUTS. RESULTS: The overall prevalence of moderate to
      severe LUTS was 15.8% (13.2% moderate and 2.6% severe). The prevalence of LUTS
      increased strongly with age, from approximately 5% among men aged < 40 years to >
      30% when aged > or = 70 years. Factors positively associated with an increased
      risk of moderate and severe LUTS were anthropometric (body mass index and waist
      hip ratio) and lifestyle factors (alcohol consumption and smoking), as well as
      comorbid conditions, including diabetes, history of stroke, muscle complaints and
      osteoarthritis. CONCLUSION: The findings from this population-based study suggest
      that the prevalence of LUTS among men aged > or = 20 years may be lower than
      previously estimated. Although LUTS may be viewed as an inevitable consequence of
      ageing, it appears to be exacerbated by lifestyle factors and comorbid
      conditions.

PMID- 15963128
TI  - A prospective randomized trial comparing transurethral prostatic resection and
      clean intermittent self-catheterization in men with chronic urinary retention.
AB  - OBJECTIVE: To determine whether a preliminary period of clean intermittent self
      catheterization (CISC) before transurethral resection of the prostate (TURP)
      improves bladder contractility and surgical outcome in men with chronic urinary
      retention (CUR), and whether pressure-flow studies (PFS) before TURP predict the
      outcome. PATIENTS AND METHODS: The study was a two-centre, pragmatic and
      randomized trial. Included were 41 men scheduled for TURP with lower urinary
      tract symptoms (LUTS), an International Prostate Symptom Score (IPSS) of > 7,
      benign prostatic enlargement and a persistent postvoid residual urine volume
      (PVR) of > 300 mL. They had conventional PFS using unphysiological filling. The
      patients then gave consent and were randomized into two treatment groups; the
      first had TURP after stabilizing renal function by indwelling catheterization if
      indicated, and the second was taught CISC. Men in both groups were reviewed at 3
      and 6 months after surgery or the start of CISC, by the IPSS, urine culture and
      assay of plasma creatinine, and upper tract imaging and repeat PFS at 6 months.
      The primary outcome variables were IPSS, maximum urinary flow rate, voiding and
      end-filling pressures, and mean PVR; secondary variables included treatment
      failure, complications and other urodynamic measures. RESULTS: Of the 41
      patients, 17 (mean age 67 years, range 52-84) were randomized to immediate TURP
      and 24 (mean age 69 years, range 55-85) to CISC. There was a significant
      improvement in IPSS and quality of life at 6 months in both groups (P < 0.001).
      In the CISC group there was a significant improvement in voiding and end-filling
      pressures, indicating recovery of bladder function (P < 0.001 for each). Of the
      41 men, nine (22%) with voiding pressures of < or = 45 cmH2O had no significant
      improvement in symptoms or urodynamic variables. Detrusor overactivity was found
      in 17 (41%) patients, of whom six had upper tract dilatation which resolved after
      treatment. CONCLUSION: The present results emphasize the usefulness of CISC in
      ensuring the recovery of bladder function in men with CUR. Measuring the voiding
      pressure before TURP can predict the surgical outcome. Both CISC and immediate
      TURP are effective for relieving LUTS and result in a better quality of life. A
      preliminary period of CISC before TURP for men with CUR and low voiding pressure
      may be valuable. The presence of upper tract dilatation is associated with high
      end-void and end-fill bladder pressures, and such men have a good outcome from
      surgery.

PMID- 15963129
TI  - Preoperative administration of chlormadinone acetate reduces blood loss
      associated with transurethral resection of the prostate: a prospective randomized
      study.
AB  - OBJECTIVES: To assess the effects of giving chlormadinone acetate (CMA) before
      surgery on blood loss associated with transurethral resection of the prostate
      (TURP), in a prospective randomized controlled study. PATIENTS AND METHODS:
      Candidates for TURP among patients with benign prostatic hyperplasia were
      randomized to either treatment with CMA (CMA+) or not (CMA-). In principle, CMA
      was started at least 28 days before TURP and continued until just before surgery.
      RESULTS: In all, 33 patients in the CMA+ (median duration of treatment 34.5 days)
      and 38 in the CMA- group were evaluable. The mean blood loss during TURP was less
      in the CMA+ (237.3 mL) than in the CMA- group (263.1 mL), but the difference was
      not significant. There was significantly less blood loss per gram of resected
      prostate tissue in the CMA+ (9.6 mL/g) than in the CMA- group (13.3 mL/g) (P <
      0.05). Haematuria on the day of and the day after TURP was also significantly
      less severe in the CMA+ than in the CMA- group (P < 0.001 and P < 0.05,
      respectively). The mean microvessel density of resected prostate tissue was
      significantly less after CMA treatment (P < 0.001). CONCLUSIONS: CMA given for 1
      month before TURP could reduce blood loss to some extent during and after TURP,
      and this may be related to a decrease in microvessel density.

PMID- 15963130
TI  - Porcine small intestinal submucosa as a percutaneous mid-urethral sling: 2-year
      results.
AB  - OBJECTIVE: To report the 2-year follow-up results on patients treated with a
      novel minimally invasive outpatient procedure for placing a mid-urethral sling,
      using porcine small intestinal submucosa (SIS). PATIENTS AND METHODS: Thirty-four
      women with urodynamic evidence of stress urinary incontinence (SUI, 19) or of SUI
      with a positive cough test (15) were treated. A curved ligature carrier was used
      to create a tract between bilateral suprapubic stab incisions and a 2-cm mid
      urethral vaginal incision. A suture secured to each end of the SIS sling was
      placed through the eyelet of the ligature carrier. Extraction was used to
      position the sling at the mid-urethra, providing a backboard of support that was
      remodelled with ingrowth of the patient's autologous tissue. RESULTS: SUI was
      reportedly cured in 27 of the 34 women (79%) at the 2-year follow-up; three (9%)
      of those with no complete resolution were pleased with their results, because the
      improvement allowed them to wear an average one or fewer pads per day. One
      patient developed de novo urge incontinence. Three patients (9%) developed
      suprapubic inflammation at 10, 21 and 45 days after surgery; all resolved, but
      one had a recurrence of SUI. No prolonged retention, erosion or other
      complications were noted. CONCLUSIONS: Early results with the percutaneous mid
      urethral placement of SIS are promising and potentially comparable with those
      after using synthetic minimally invasive slings.

PMID- 15963131
TI  - Hyperbaric oxygen therapy for radiation-induced haemorrhagic cystitis.
AB  - OBJECTIVE: To assess the efficacy of hyperbaric oxygen (HBO) for treating
      haemorrhagic cystitis. PATIENTS AND METHODS: From February 1997 to April 2004,
      seven patients with radiation-induced haemorrhagic cystitis were treated with
      HBO; they received a mean (range) of 30 (18-57) HBO treatments and the follow-up
      was 24 (3-53) months. RESULTS: The haematuria resolved completely in all seven
      patients shortly after treatment; one had an improvement but died from
      complications relating to cancer shortly after completing treatment, and two had
      recurrence of gross haematuria. They were re-treated with HBO until the
      haematuria resolved. CONCLUSIONS: Radiation-induced haemorrhagic cystitis can be
      treated successfully with HBO primarily or after failure of standard regimens.
      This method was well tolerated even in patients debilitated by advanced cancer
      and blood loss. Long-term remission is possible in most patients, and re
      treatment effectively manages recurrent bleeding.

PMID- 15963132
TI  - Magnetic resonance imaging as a sole method for the morphological and functional
      evaluation of live kidney donors.
AB  - OBJECTIVE: To evaluate gadolinium-enhanced dynamic magnetic resonance imaging
      (MRI) as the sole method for the anatomical and functional assessment of
      potential live-kidney donors. SUBJECTS AND METHODS: The study included 50
      consecutive kidney donors; in addition to routine donor evaluation, the kidney
      was imaged with Gd-enhanced dynamic MRI, which was also used for selectively
      determining the glomerular filtration rate (GFR) of each kidney. All donors had a
      m99Tc-mercaptoacetyltriglycine (MAG3) renal scan as the reference standard to
      measure GFR. The anatomical results of MRI were compared with the findings at
      donor nephrectomy, and the GFR estimated from MRI compared with that from MAG3
      scintigraphy. RESULTS: MR angiography had 100% sensitivity, 94% specificity and
      96% overall accuracy for detecting the number of renal arteries, and 100%
      sensitivity, 98% specificity and 98% overall accuracy for the number of renal
      veins. There was a close correlation (r = 0.54, P < 0.01) between the GFR of each
      kidney estimated by MRI or MAG3. For the right and left kidneys the mean isotope
      clearance was not significantly different from that of mean MRI clearance. MR
      urography allowed visualization of the urinary tract and the detection of any
      abnormality. CONCLUSION: Gd-enhanced dynamic MRI can provide accurate information
      about the anatomy of the urinary tract and vasculature of the kidney, and can be
      used to accurately estimate the selective GFR of each kidney. Therefore, we
      recommend MRI as a single imaging diagnostic method for assessing potential live
      kidney donors.

PMID- 15963133
TI  - Vitamin E therapy prevents hyperoxaluria-induced calcium oxalate crystal
      deposition in the kidney by improving renal tissue antioxidant status.
AB  - OBJECTIVE: To determine whether vitamin E prevents hyperoxaluria-induced stone
      formation, using a new animal model of calcium oxalate stone disease, as our
      previous in- vitro and in-vivo studies showed that oxalate and hyperoxaluria
      induce free-radical generation, which results in peroxidative injury to renal
      tubular cells. MATERIALS AND METHODS: Ethylene glycol (EG) was administered at
      150 mg/day by gavage for 3 weeks to rats fed on diets with adequate (group 1),
      excess (group 2) or deficient (group 3) vitamin E. Several indicators of
      peroxidation, free radicals and enzymatic activity were then assessed. RESULTS:
      EG treatment in group 1 lead to increased lipid peroxidation, protein thiol,
      excretion of urinary enzymes, oxalate and decreases in urinary calcium,
      antioxidant enzymes and altered glutathione redox balance. Although renal
      function was not altered, there was increased water intake, urine volume and
      lowered urinary pH in these rats. These changes were more intense, with extensive
      calcium-oxalate crystal deposition, in rats in group 3, and prevented in rats in
      group 2, except for urinary oxalate levels, which remained high.
      Histopathological examination showed that there was no deposition of calcium
      oxalate crystals in rats in group 2. CONCLUSION: This is the first study to
      demonstrate in-vivo evidence that hyperoxaluria-induced peroxidative injury
      induces individual calcium oxalate crystal attachment in the renal tubules. In
      addition, excess vitamin E completely prevented calcium oxalate deposition, by
      preventing peroxidative injury and restoring renal tissue antioxidants and
      glutathione redox balance. Therefore, vitamin E therapy might provide protection
      against the deposition of calcium oxalate stones in the kidney of humans.

PMID- 15963134
TI  - Treatment of pelvic fracture-related urethral trauma: a survey of current
      practice in the UK.
AB  - OBJECTIVE: To quantify experience of pelvic fracture-related urethral trauma
      (PFUT), a condition not often encountered and managed by urologists. METHODS: The
      consultant urologists of the UK and Ireland were contacted informally to
      establish their experience with PFUT and its management, both immediate and
      delayed. In addition, particular individuals thought to have a specific interest
      in PFUT were targeted for more data. RESULTS: The overall response rate was 49%
      (235 responders), representing 78% of urological departments, including all the
      targeted individuals. Of the responders, 129 (55%) had never seen PFUT in 1-25
      years of consultant practice. Only four urologists (2% of responders) saw three
      or more cases a year. Another four (2%) saw one or two cases per year and the
      remaining 98 (41%) saw PFUT less frequently. Acutely, 69% of urologists who
      treated PFUT did so by placing a urethral catheter. Subsequent strictures were
      treated endoscopically for as long as this was possible. The other 31% inserted a
      suprapubic catheter and referred the patient for reconstructive surgery if
      needed. Those who used urethroplasty for strictures after PFUT were identified
      and targeted; half used urethral mobilization and spatulated anastomosis alone.
      Only three surgeons performed more than five procedures a year. CONCLUSION:
      Whatever a specialist reconstructive unit might do, practice in the wider
      urological community is different. Even within specialized units, PFUT is rare
      and the surgical management is often significantly different from published
      'expert' opinion.

PMID- 15963135
TI  - Upper and lower urinary tract outcome after surgical repair of cloacal
      malformations: a three-decade experience.
AB  - OBJECTIVE: To report the urological outcome of the surgical correction of
      persistent cloaca, which is technically demanding and may require many procedures
      in an effort to preserve renal function and provide urinary continence. PATIENTS
      AND METHODS: A retrospective chart review from 1971 to 2003 identified 23
      patients with cloacal malformations (two posterior, 21 classical) that were
      reconstructed. The confluence of the urethra, vagina and rectum was noted to be
      high in 16, low in five and unknown in two; one patient was a conjoined twin.
      RESULTS: The mean (range) follow-up was 9.3 (0.4-31.6) years. Urinary anomalies
      included 14 patients with renal anomalies (six solitary kidneys, four renal
      dysplasia, two pelvi-ureteric junction, one each duplex and crossed fused) and
      two duplicated bladders. Vesico-ureteric reflux was present in 13 patients (57%),
      hydronephrosis at birth in 13, a bony vertebral abnormality in 14 and the VACTERL
      association in four. Total urogenital mobilization (TUM) was used in six patients
      and spinal cord untethering in four; a nephrectomy was required in three and
      partial nephrectomy in one. Upper tract dilation was still present in six
      patients. Age-adjusted creatinine levels were abnormal in four (18%) patients and
      borderline in another six (26%). In the nine patients with a solitary kidney (six
      solitary, three after nephrectomy), the age-adjusted creatinine level was
      abnormal in two and borderline in four. A vesicostomy was initially performed in
      11 patients. The method of bladder emptying is known in 22; 10 void, 11 require
      clean intermittent catheterization (five abdominal stoma, six urethral) and one
      was diverted with a conduit. Of the 18 patients aged > 47 months 15 were
      continent (14 complete > 4 h, one partial 2-4 h), and three are wet (one
      conduit). Reconstruction of the lower urinary tract included four bladder
      augmentations (one ureteric, one ileal, two colon), five bladder neck procedures
      (two artificial sphincter, one each bladder neck repair, sling, bladder neck
      division) and six catheterizable channels (one now with a colon conduit). The
      ureters were re-implanted in 12 patients. CONCLUSION: Although the surgical
      correction of this rare malformation is complex, the upper urinary and lower
      urinary tract outcome can be favourable, albeit after several reconstructive
      procedures. TUM has emerged as the primary method for vaginal reconstruction, but
      the long-term lower tract outcome after this procedure is awaited.

PMID- 15963136
TI  - An objective assessment of the results of hypospadias surgery.
AB  - OBJECTIVE: To compare the cosmetic result of tubularized incised-plate
      urethroplasty (Snodgrass method) with that of two established techniques, the
      meatal-based flap and onlay island flap repair. SUBJECTS AND METHODS: Photographs
      of the penis after hypospadias repair in 32 boys were assessed by a panel of five
      independent health professionals, including four surgeons with variable
      paediatric urological experience and a urology nurse. Twenty patients had a
      distal and 12 a proximal meatus. The Snodgrass technique was applied by one
      paediatric urologist for either distal (10) or proximal (six) hypospadias. A
      Mathieu repair was used for distal hypospadias (10) and an onlay preputial island
      flap for proximal hypospadias (six) by a second paediatric urologist. The panel
      was asked to grade cosmesis as poor, unsatisfactory, satisfactory or very good
      (points 1-4) for each of the following aspects of penile appearance: meatus,
      glans, shaft and overall appearance. Photographs were taken in a standard way,
      with a standard distance, lighting and two views, one of the dorsal surface and
      one ventral, for each patient. Signed written consent for the study was obtained
      from each family. RESULTS: The mean assessment score for any aspect of cosmesis
      was significantly higher for the Snodgrass technique (P < 0.05). The mean score
      (95% confidence interval) for the meatus was 0.76 (0.4-1.1) points higher for the
      patients with a Snodgrass repair than those with a Mathieu or onlay island flap
      repair (P = 0.002). Correspondingly, the values for the glans were 0.67 (0.38
      0.97) (P = 0.003), shaft 0.42 (0.16-0.69) (P = 0.01) and overall appearance 0.62
      (0.24-1.0) (P = 0.01) points higher for the Snodgrass repair. The Snodgrass
      technique was more effective in producing a vertically orientated meatus (87.5%)
      than the Mathieu and Duckett onlay repairs (37.5%; P = 0.009). CONCLUSION: The
      Snodgrass technique, as assessed by this panel, had a better cosmetic outcome
      than the Mathieu and Duckett onlay island flap repairs. The assessment of
      cosmesis in hypospadias surgery is potentially more objective when several health
      professionals, not involved in the surgery, compared the various methods of
      repair.

PMID- 15963137
TI  - Myogenic bladder decompensation in boys with a history of posterior urethral
      valves is caused by secondary bladder neck obstruction?
AB  - OBJECTIVE: To investigate whether myogenic bladder decompensation in patients
      treated for congenital posterior urethral valves (PUV, the most serious cause of
      infravesical obstruction in male neonates and infants) may be secondary to
      bladder neck obstruction, as despite prompt ablation of PUV these patients can
      have dysfunctional voiding during later childhood or adolescence, the so-called
      'valve bladder syndrome'. PATIENTS AND METHODS: The study comprised 18 boys (mean
      age 14 years, range 6.2-18.5) who had had successful transurethral ablation of
      PUV between 1982 and 1996, and had completed a follow-up which included serial
      assessment of serum creatinine, completion of a standard voiding diary,
      ultrasonography with measurement of urine before and after voiding, a urodynamic
      examination with simultaneous multichannel recording of pressure, volume and flow
      relationships during the filling and voiding phases, coupled with video
      cystoscopy at least twice. The mean (range) follow-up was 9.3 (6-17) years.
      RESULTS: Urodynamic investigation showed myogenic failure with inadequate bladder
      emptying in 10 patients; five with myogenic failure also had unstable bladder
      contractions. On video-cystoscopy the posterior bladder neck lip appeared
      elevated in all patients but in those with myogenic failure it was strongly
      suggestive of hypertrophy, with evidence of obstruction. At the last follow-up
      one patient with myogenic failure who had had bladder neck incision and four
      others who were being treated with alpha-adrenergic antagonists had a significant
      reduction of their postvoid residual urine. CONCLUSION: Despite early valve
      ablation, a large proportion of boys treated for PUV have gradual detrusor
      decompensation, which may be caused by secondary bladder neck obstruction leading
      to obstructive voiding and finally detrusor failure. Surgical or pharmacological
      intervention to improve bladder neck obstruction may possibly avert this course,
      but further studies are needed to validate this hypothesis.

PMID- 15963138
TI  - Expression of Ki-67 in squamous cell carcinoma of the penis.
AB  - OBJECTIVE: To investigate the Ki-67 labelling index (LI) as a prognostic factor
      for the outcome of penile carcinoma, as in squamous cell carcinoma (SCC) of the
      larynx the expression of this marker correlates with histological features
      indicative of prognosis. PATIENTS AND METHODS: We retrospectively analysed the
      records of 44 patients in whom primary SCC of the penis was treated with
      amputation and bilateral lymphadenectomy (pT1, in 24, pT2 in 20, pN+ in 10; G1 in
      12, G2 in 28 and G3 in four). During a mean follow-up of 35.6 months, four
      patients had disease progression. Tumour tissue was stained immunohistochemically
      using the streptavidin-biotin method. The mean Ki-67 LI was defined as the
      percentage of total tumour cells that were Ki-67-positive. The results were
      compared with pathological tumour stage, grade, nodal status and clinical disease
      progression. RESULTS: The mean (range) Ki-67 LI was 40.5 (6.4-93.0)%; a high mean
      Ki-67 LI was significantly inversely correlated with tumour differentiation (P <
      0.005) and there was a tendency for a high Ki-67 LI to be associated with
      advanced local tumour stage, nodal metastasis and clinical disease progression,
      but these correlations were not statistically significant (P = 0.07, 0.07 and
      0.06, respectively). CONCLUSIONS: The Ki-67 LI is correlated with tumour grade in
      penile cancer, and may indicate a greater risk of nodal metastasis.

PMID- 15963139
TI  - Accuracy of the routine detection of mutation in mismatch repair genes in
      patients with susceptibility to hereditary upper urinary tract transitional cell
      carcinoma.
AB  - OBJECTIVE: To establish the clinical benefits of systematic testing for hMSH6 and
      hMLH1 mutations in the very rare patients with upper urinary tract transitional
      cell carcinomas (UUT-TCCs), a clinical predisposition for hereditary tumour and
      no mutation detected in hMSH2 gene. PATIENTS AND METHODS: In all, 164 UUT-TCC
      specimen blocks were screened for microsatellite instability (MSI); 27 (16%) had
      high MSI levels. Eight patients (30%) had clinical criteria suspicious of
      hereditary tumour; in three a mutation in hMSH2 was detected. For the other
      patients, clinical data were collated, and DNA gene sequences analysed to detect
      mutations in hMLH1 and in hMSH6 genes. RESULTS: Five patients were assessed (mean
      age at the diagnosis of UUT-TCC 65.2 years, sd 8, range 54-71; two aged < 60
      years). Three patients had a personal history of hereditary nonpolyposis
      colorectal related-cancer (three colorectal). There were only mutations in hMSH2
      gene detected, with none in hMSH6 and hMLH1. CONCLUSION: For the rare patients
      with UUT-TCC who are suspected of carrying mismatch repair gene mutations if no
      hMSH2 mutation is found by genetic testing, complementary DNA sequencing for
      hMLH1 and hMSH6 mutation does not seem to contribute and should not be
      recommended in daily practice.

PMID- 15963140
TI  - Mesenchymal cells infiltrating a bladder acellular matrix gradually lose smooth
      muscle characteristics in intraperitoneally regenerated urothelial lining tissue
      in rats.
AB  - OBJECTIVE: To characterize serial long-term histological changes in mesenchymal
      cells infiltrating a collagen-based matrix, as in a hollow organ with
      differentiated urothelial lining created intraperitoneally by grafting cultured
      urothelial cells, mesenchymal cells with smooth-muscle immunohistochemical
      characteristics infiltrated into the scaffold, despite no mesenchymal cells being
      seeded into the scaffold before grafting. MATERIALS AND METHODS: To regenerate a
      urothelial lining tissue intraperitoneally, rat urothelial cells were cultured
      and seeded with the feeder-layer technique onto bladder acellular matrix (BAM).
      After 7 days of cultivation to attach urothelial cells on the BAM, the matrix was
      folded with the urothelial cells inside and grafted onto the mesentery of the
      previously partially cystectomized rat. RESULTS: The grafted urothelial cells on
      the BAM, which formed a monolayer before grafting, stratified into three to four
      layers as early as 4 days after grafting. Although the regenerated urothelium
      became thinner with time, there was urothelial stratification and a peculiar
      angular appearance on the apical surface of the regenerated urothelium even after
      56 days. The mesenchymal cells infiltrating the BAM showed positive
      immunohistochemical staining to alpha-smooth muscle actin or desmin at 7 days.
      Subsequently, the number of actin- or desmin-positive cells gradually decreased
      with time. On transmission electron microscopy, the infiltrating mesenchymal
      cells were characterized as myofibroblasts at 7 days. Smooth muscle-like cells
      were identified at 14 and 28 days, and fibrocytes were the main population at 56
      days. CONCLUSIONS: Although epithelial-mesenchymal interactions have been assumed
      to be one of the most critical factors in smooth-muscle development, mesenchymal
      cells infiltrating the scaffold in this intraperitoneal regeneration model
      gradually lost smooth muscle characteristics with time. These results suggest
      that interactions between cultured urothelial cells and infiltrating mesenchymal
      cells alone could not maintain the smooth muscle character of infiltrating
      mesenchymal cells.

PMID- 15963141
TI  - Apoptosis: a key effector mechanism of lymphocyte action in human nonseminomatous
      testicular carcinoma?
AB  - OBJECTIVE: To correlate the number of tumour-infiltrating T lymphocytes (TILs)
      with the extent of apoptosis in testicular germ cell tumours, as TILs are
      considered to be a favourable prognostic factor of human testicular tumours,
      especially of seminomas, but the mechanism by which TIL contribute to an improved
      outcome is unclear. MATERIALS AND METHODS: Tissue samples from 47 patients with
      nonseminomatous germ cell tumour (NSGCT) and 15 with seminomatous GCT were
      investigated immunohistochemically for lymphocyte infiltration and apoptosis. The
      apoptotic index (AI) was assessed in various categories (DNA condensation and
      fragmentation) using in-situ end-labelling to identify typical apoptotic DNA
      strand breaks, and nuclear staining to identify typical apoptotic morphology.
      RESULTS: In seminomatous GCT there was no correlation between the number of TILs
      and any AI. In NSGCT there was only a relationship between lymphoid infiltration
      and those AIs showing morphological criteria of apoptosis in a small subgroup of
      NSGCT, i.e. metastasized embryonal cell carcinomas. Only 1.2% (AI, chromatin
      condensation) and 0.8% (AI, fragmentation and condensation) of all tumour cells
      showed these features of apoptosis. The overall AI in NSGCT was 7.9%.
      CONCLUSIONS: TILs do not seem to induce apoptosis in testicular tumours.
      Embryonal cell carcinomas might be susceptible to lymphocyte attack, resulting in
      apoptosis of the tumour cell. The mechanisms of interaction between lymphocytes
      and testis tumour cells need further investigation.

PMID- 15963142
TI  - In vivo and in vitro response of corpus cavernosum to phosphodiesterase-5
      inhibition in the hypercholesterolaemic rabbit.
AB  - OBJECTIVE: To investigate the effects of hypercholesterolaemia (HC) on rabbit
      corpus cavernosa in vivo and in vitro, and evaluate the efficacy of vardenafil
      and sildenafil in normal and HC rabbits, as the phosphodiesterase-5 (PDE-5)
      inhibitors vardenafil and sildenafil are widely used for treating erectile
      dysfunction (ED) and most organic causes of ED are associated with vascular risk
      factors like HC. MATERIALS AND METHODS: Male New Zealand White rabbits were
      randomly divided into two groups; 11 HC rabbits were fed a 2% cholesterol diet,
      and 12 age-matched control rabbits received a regular diet. After 12-14 weeks,
      erectile responses to intravenous sodium nitroprusside (SNP) and PDE-5 inhibitors
      were evaluated for 2 h in conscious rabbits. Penile length was measured and the
      area under the curve calculated. Relaxant responses of corpus cavernosal strips
      to electrical-field stimulation (EFS) were measured before and after exposure to
      PDE-5 inhibitors and the nitric oxide synthase inhibitor N'-nitro-L-arginine
      methyl ester. RESULTS: HC rabbits had a lower erectile response to SNP than
      controls; in both control and HC rabbits there was a greater erectile response
      after simultaneous exposure to SNP and vardenafil, or SNP and sildenafil.
      However, the responses of the HC rabbits were still significantly less than those
      of the controls. Corpora from control rabbits responded to EFS with greater
      relaxations at all frequencies, except 1 Hz. Corpora from both HC and control
      rabbits had greater responses to EFS after exposure to vardenafil and sildenafil;
      N'-nitro-L-arginine methyl ester diminished the response to EFS. CONCLUSIONS:
      There was a significantly lower in vivo and in vitro erectile response in HC
      rabbits than in controls; erectile function measured in conscious rabbits can be
      used to assess quantitatively the efficacy of different agents, e.g. sildenafil
      and vardenafil, in pathological animals. In addition, both agents improve in
      vitro responses of erectile tissue from HC rabbits to EFS.

PMID- 15963143
TI  - Effect of bladder ischaemia/reperfusion on superoxide dismutase activity and
      contraction.
AB  - OBJECTIVES: To correlate the effect of bilateral in-vivo bladder
      ischaemia/reperfusion on superoxide dismutase activity (SOD) and then to
      correlate this with contractile responses to various forms of stimulation.
      MATERIALS AND METHODS: Twenty mature male New Zealand White rabbits were divided
      into five equal groups: group 1 (controls); group 2, 2 h of in-vivo bilateral
      bladder ischaemia; and groups 3-5, 2 h of in-vivo ischaemia followed by 1, 7 or
      14 days of reperfusion (recovery). At the end of the treatment period, bladder
      strips were incubated and placed in isolated baths for contractile studies. The
      contractile responses to field stimulation, carbachol (10 micromol/L), ATP and
      KCl were determined. The balance of the bladder body was separated into muscle
      and mucosa sections and analysed for SOD activity. RESULTS: There were few
      effects on contraction either directly after ischaemia or after 1 day of
      reperfusion. However, all contractile responses were significantly reduced at 7
      and 14 days after ischaemia. SOD activity of the detrusor muscle was reduced
      significantly immediately after ischaemia and at 7 and 14 days of reperfusion.
      SOD activity of the mucosa was significantly greater than that of the muscle, and
      was significantly reduced by both ischaemia and all times of reperfusion.
      CONCLUSIONS: These studies show clearly that both ischaemia and reperfusion
      result in significantly lower activity of SOD, and in contractile dysfunctions,
      and that reperfusion results in greater decreases in both SOD activity and
      contractile responses than ischaemia alone.

PMID- 15963144
TI  - Allopurinol provides long-term protection for experimentally induced testicular
      torsion in a rabbit model.
AB  - OBJECTIVE: To assess the effect of five antioxidants on exocrine function of
      rabbit testes retained in situ for 24 h and 3 months after experimental torsion.
      MATERIALS AND METHODS: The left testes of peripubertal rabbits were clamped for
      60 min, after which the clamps were removed and the testes allowed to reperfuse.
      The right testes served as internal controls. There were eight rabbits in each of
      the following experimental groups: (a) sham; (b) 60-min ischaemia followed by
      reperfusion; (c) 60-min ischaemia followed by left orchidectomy. In five further
      groups, rabbits were exposed to 60-min ischaemia followed by reperfusion, but
      received one of the following antioxidants before reperfusion: acetyl salicylic
      acid, ascorbic acid, allopurinol, quercetin or superoxide dismutase. Both testes
      were excised at 24 h or 3 months. The degree of lipid peroxidation, a measure of
      free radical damage, was assessed in testicular tissue homogenates by measuring
      the tissue levels of malondialdehyde (MDA). The Johnsen score was used to assess
      the morphological damage at 24 h and 3 months for each group. RESULTS: At 3
      months twisted viable testes allowed to reperfuse had higher MDA levels than
      controls; the left testes of rabbits treated with allopurinol had significantly
      lower MDA levels than untreated rabbits and rabbits given other antioxidants.
      Rabbits given quercetin, ascorbic acid or superoxide dismutase had lower (but not
      significantly) left testicular MDA levels than untreated rabbits, while rabbits
      given acetyl salicylic acid had even higher levels. Allopurinol-treated rabbits
      had a Johnsen score of > 7.6 and those given other antioxidants had scores of <
      7.6 at 3 months. CONCLUSION: The twisted viable testis treated by orchidopexy
      contains high free radical levels at 3 months. Of the antioxidants studied, only
      allopurinol had a beneficial long-term effect, by significantly reducing
      testicular MDA levels at 3 months.

PMID- 15963145
TI  - The era of ESSTIs is slowly approaching?

PMID- 15963146
TI  - Laparoscopic O'Conor's repair for vesico-vaginal and vesico-uterine fistulae.

PMID- 15963147
TI  - Tied and tested: a cheap and simple method for transurethral resection.

PMID- 15963150
TI  - Conventional and alternative methods for providing analgesia in renal colic.

PMID- 15963152
TI  - High-intensity focused ultrasound (HIFU) for treating prostate cancer.

PMID- 15963153
TI  - Managing patients with an overactive bladder and glaucoma: a questionnaire survey
      of Japanese urologists on the use of anticholinergics.

PMID- 15963154
TI  - Vesico-vaginal fistula.

PMID- 15963155
TI  - Surgical atlas transureteroureterostomy.

PMID- 15963157
TI  - The impact of severe acute respiratory syndrome on medical house staff: a
      qualitative study.
AB  - OBJECTIVE: To explore the impact of severe acute respiratory syndrome (SARS) on a
      medical training program and to develop principles for professional training
      programs to consider in dealing with future, similar crises. DESIGN: Qualitative
      interviews analyzed using grounded theory methodology. SETTING: University
      affiliated hospitals in Toronto, Canada during the SARS outbreak in 2003.
      PARTICIPANTS: Medical house staff who were allocated to a general internal
      medicine clinical teaching unit, infectious diseases consultation service, or
      intensive care unit. RESULTS: Seventeen medical residents participated in this
      study. Participants described their experiences during the outbreak and
      highlighted several themes including concerns about their personal safety and
      about the negative impact of the outbreak on patient care, house staff education,
      and their emotional well-being. CONCLUSION: The ability of residents to cope with
      the stress of the SARS outbreak was enhanced by the communication of relevant
      information and by the leadership of their supervisors and infection control
      officers. It is hoped that training programs for health care professionals will
      be able to implement these tenets of crisis management as they develop strategies
      for dealing with future health threats.

PMID- 15963158
TI  - Perceived preparedness to provide preventive counseling: reports of graduating
      primary care residents at academic health centers.
AB  - OBJECTIVE: To assess the perceived preparedness of residents in adult primary
      care specialties to counsel patients about preventive care and psychosocial
      issues. DESIGN: Cross-sectional national mail survey of residents (63% response
      rate). PARTICIPANTS: Nine hundred twenty-eight final-year primary care residents
      in Internal Medicine (IM), family practice (FP), and Obstetrics/Gynecology
      (OB/GYN) at 162 U.S. academic health centers. MEASUREMENTS: Residents self-rated
      preparedness to counsel patients about smoking, diet and exercise, substance
      abuse, domestic violence, and depression. RESULTS: Residents felt better prepared
      to counsel about smoking (62%) and diet and exercise (53%) than about depression
      (37%), substance abuse (36%), or domestic violence (21%). In most areas, females
      felt better prepared than males. Rates of counseling preparedness varied
      significantly by specialty after adjustment for gender, race, medical school
      location, and percent of training spent in ambulatory settings. FP residents felt
      better prepared than OB/GYN residents to counsel about smoking, diet and
      exercise, and depression, while OB/GYN residents felt better prepared to address
      domestic violence than IM or FP residents. IM residents' perceptions of
      preparedness were between the other 2 specialties. Proportion of training spent
      in ambulatory settings was not associated with residents' perceived preparedness.
      CONCLUSIONS: Physicians completing residencies in adult primary care did not feel
      very well prepared to counsel patients about preventive and psychosocial issues.
      Significant differences exist among specialties, even after adjusting for
      differences in time spent in ambulatory settings. Increasing residency time in
      ambulatory settings may not alone be sufficient to ensure that residents emerge
      with adequate counseling skills.

PMID- 15963159
TI  - A survey of health care practitioners' knowledge of the QT interval.
AB  - OBJECTIVE: To assess health care practitioners' ability to correctly measure the
      QT interval, and to identify factors and medications that may increase the risk
      of QT-interval prolongation and torsades de pointes. DESIGN: A cross-sectional
      analysis of a survey administered between April 2002 and March 2003. PARTICIPANTS
      AND SETTING: Health care practitioners attending Grand Rounds Conferences at 6
      academic institutions in the United States in internal medicine and psychiatry
      and at 6 community hospitals in the same geographical areas as the academic
      institutions. INTERVENTION: Anonymous, self-administered questionnaire that
      included 20 questions on the QT interval. MEASUREMENTS AND MAIN RESULTS: Of
      approximately 826 attendees, 517 (63%) completed the survey. Of about 608
      attendees of internal medicine conferences, 371 (61%) responded, and of about 208
      attendees of psychiatry conferences, 146 (67%) responded. Of a total number of 20
      questions, the median number of correct answers for the whole group was 10
      (interquartile range 7-13). The median number of correct answers for internists
      was 12 (interquartile range 9-13), for psychiatrists 10 (interquartile range 7
      13), and for other specialists 10 (interquartile range 5-13). Respondents who
      graduated between 1990 and 1999 and academicians performed significantly better
      overall than other respondents. Of the 517 respondents, 224 (43%) measured the QT
      interval correctly. Physicians in training and academicians were more likely to
      measure the QT interval correctly. CONCLUSION: The majority of health care
      practitioners cannot correctly measure the QT interval and cannot correctly
      identify factors and medications that can prolong the QT interval. Our findings
      suggest that greater attention to the QT interval is warranted to ensure safer
      use of QT prolonging medications.

PMID- 15963160
TI  - Depression and suicidal behaviors in Medicare primary care patients under age 65.
AB  - OBJECTIVE: To examine suicidal behavior and depression prevalence among a group
      of Medicare patients under age 65 with functional impairment and recent
      significant health care services use. DESIGN: An observational study of baseline
      characteristics of participants in a randomized controlled trial. SETTING: A
      Medicare demonstration (N=1,605) that enrolled primary care patients in 8
      counties in New York, 6 counties in West Virginia, and 5 counties in Ohio.
      PATIENTS/PARTICIPANTS: All demonstration participants under age 65 (n=164).
      Participants were required to have impairment in at least 2 activities of daily
      living or 3 instrumental activities of daily living, and to have had recent
      significant health care use. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      The Paykel questionnaire for suicidal ideation and attempts, the Mini
      international Neuropsychiatric Interview Major Depressive Episode module, and the
      15-item Geriatric Depression Scale were administered at baseline; 14.8% of the
      patients indicated suicidal ideation during the past year, 4.9% reported a
      suicide attempt during that time, 25.9% indicated at least 1 lifetime suicide
      attempt, 34.6% had a major depressive episode in the last month, and 58.3% had
      clinically significant depressive symptoms during the previous week. CONCLUSIONS:
      These levels of suicidal ideation and behaviors and of depression are far higher
      than those found in studies of nonelderly American adults, and may indicate the
      need for routine screening in this population.

PMID- 15963161
TI  - Beyond the medical record: other modes of error acknowledgment.
AB  - BACKGROUND: Studies before and since the 1999 Institute of Medicine report have
      noted the limitations of using medical record reporting for reliably quantifying
      and understanding medical error. Quantitative macro analyses of large datasets
      should be supplemented by small-scale qualitative studies to provide insight into
      micro-level daily events in clinical and hospital practice that contribute to
      errors and adverse events and how they are reported. DESIGN: The study design
      involved semistructured face-to-face interviews with residents about the medical
      errors in which they recently had been involved and included questions regarding
      how those errors were acknowledged. OBJECTIVE: This paper reports the ways in
      which medical error is or is not reported and residents' responses to a perceived
      medical error. PARTICIPANTS: Twenty-six residents were randomly sampled from a
      total population of 85 residents working in a 600-bed teaching hospital.
      MEASUREMENTS: Outcome measures were based on analysis of cases residents
      described. Using Ethnograph and traditional methods of content analysis, cases
      were categorized as Documented, Discussed, and Uncertain. RESULTS: Of 73 cases,
      30 (41.1%) were formally acknowledged and Documented in the medical record; 24
      (32.9%) were addressed through Discussions but not documented; 19 cases (26%)
      cases were classified as Uncertain. Twelve cases involved medication errors,
      which were acknowledged in different categories. CONCLUSIONS: The supervisory
      discussion, the informal discussion, and near-miss contain important information
      for improving clinical care. Our study also shows the need to improve residents'
      education to prepare them to recognize and address medical errors.

PMID- 15963162
TI  - Stage of readiness to control weight and adopt weight control behaviors in
      primary care.
AB  - BACKGROUND: While the majority of adults are attempting weight loss at any given
      time, few engage in optimal diet and exercise. We examined factors associated
      with being in advanced stages of behavior change for weight loss, diet, and
      exercise. METHODS: We surveyed primary care patients about their health, health
      habits, and perception and advice about weight as health risk, and about stage of
      readiness to lose weight, improve diet (control food portions, limit fat intake,
      increase fruits and vegetables), and increase planned exercise using the
      Prochaska Stage of Behavior Change model. We conducted bivariable analyses to
      describe the association between being at the preparation (change in 1 month),
      action (changing now), and maintenance (maintaining change) stages of change for
      weight loss and being at 1 of these 3 advanced stages for improving diet and
      exercise. We also conducted multivariable analyses to examine factors associated
      with being at these advanced stages of readiness to concurrently lose weight,
      improve diet, and increase exercise. RESULTS: Of 365 patients (response rate of
      60%), 33% were overweight (body mass index [BMI], 25.0-29.9 kg/m(2)) and 27% were
      obese (BMI, 30.0+kg/m(2)). Of 199 respondents at the preparation, action, or
      maintenance stage of losing weight, 61% were also at an advanced stage for
      improving diet and exercise. Those perceiving weight as a health risk were more
      likely to be at advanced stages of readiness to concurrently lose weight, improve
      diet, and increase exercise (adjusted odds ratio [AOR], 5.6; 95% CI, 2.5 to 12.5)
      after adjustment for confounders; this perception was associated with BMI ([AOR,
      1.2; 95% CI, 1.1 to 1.3 for each unit increment in BMI]) and being advised by a
      physician about weight as a health risk (AOR, 6.7; 95% CI, 3.0 to 15.1).
      Demographic factors, having obesity-related comorbidities, and mental and
      physical functioning did not appear important. CONCLUSIONS: A large proportion of
      primary care patients are at advanced stages of readiness to lose weight, improve
      diet, and increase exercise. Future studies should examine the effectiveness of
      primary care interventions to help patients optimize weight-related behavior.

PMID- 15963163
TI  - Brief report: attitudes toward hormone therapy after the Women's Health
      Initiative: a comparison of internists and gynecologists.
AB  - In the Women's Health Initiative (WHI), postmenopausal women receiving
      combination hormone therapy (HT) experienced more adverse outcomes than placebo
      recipients. To determine whether gynecologists and internists interpreted the WHI
      differently, we conducted a survey in which physicians responded to a
      hypothetical asymptomatic woman who asks whether to continue HT. In response to
      this scenario, gynecologists were more likely than internists to hold permissive
      views about prescribing HT (66% vs 35%; P<.001). These results suggest that
      gynecologists may be less concerned than internists about the adverse events
      associated with HT, or that gynecologists have stronger beliefs about benefits of
      HT.

PMID- 15963164
TI  - Brief report: needlestick injury and inadequate post-exposure practice in medical
      students.
AB  - BACKGROUND: Medical students are at a particularly high risk for needlestick
      injury and its consequences because of their relative inexperience and lack of
      disability insurance. OBJECTIVE: To determine the risk of needlestick injury and
      the use of post-exposure prophylaxis among medical students. DESIGN: Internet
      based survey. PARTICIPANTS: The 2003 graduating medical school class at the
      University of Toronto. MEASUREMENTS: Number of needlestick injuries,
      circumstances surrounding those incidents, and post-exposure actions. RESULTS:
      The response rate was 88% (157/178). Over one third (55/157) of respondents
      suffered at least 1 needlestick injury. In more than half the high-risk injuries,
      the students continued working and did not seek medical advice. Six students who
      suffered a needlestick injury began prophylactic human immunodeficiency virus
      medications. Of those students who suffered an injury, 15% had purchased
      disability insurance prior to the incident. CONCLUSIONS: Poor use of post
      exposure procedures and a lack of disability insurance leave medical students at
      high risk for career and life-altering consequences from a needlestick injury.

PMID- 15963165
TI  - Low health literacy is associated with HIV test acceptance.
AB  - BACKGROUND: The Centers for Disease Control and Prevention has proposed
      increasing the proportion of people who learn their HIV serostatus. The health
      care setting represents a logical site to accomplish this goal. However, little
      is known about factors that determine acceptability of HIV testing in health care
      settings, particularly patients' health literacy. OBJECTIVE: To evaluate the
      association between patients' health literacy and acceptance of HIV testing among
      individuals at an urgent care center (UCC). METHODS: As part of a prospective
      study that sought to increase HIV testing at a UCC located in an inner-city
      hospital serving an indigent population, we surveyed patients who had been
      offered an HIV test by their providers and had accepted or refused testing.
      Pretest counseling was provided using a low-literacy brochure given to patients
      upon registration into the clinic. We measured health literacy level using the
      Rapid Estimate of Adult Literacy in Medicine (REALM) scale. RESULTS: Three
      hundred seventy-two patients were enrolled in the study. In univariate analysis,
      no statistically significant difference between HIV test acceptors or refusers
      was found for gender, race/ethnicity, marital status, income, type of health
      insurance, educational level, or type of test offered. Acceptors were more likely
      to have a low literacy level (odds ratio [OR], 1.763; 95% confidence interval
      [CI], 1.084 to 2.866) and be less than 40 years old (OR, 1.639; 95% CI, 1.085 to
      2.475). In multivariate analysis, low health literacy was shown to be a predictor
      of HIV test acceptance controlling for age and education (OR, 2.017; 95% CI,
      1.190 to 3.418). CONCLUSIONS: Low health literacy was shown to be a predictor of
      HIV test acceptance. Patients presenting to a UCC with poorer health literacy
      appear more willing to comply with health care providers' recommendations to
      undergo HIV testing than those with adequate health literacy when an "opt-out"
      strategy combined with a low-literacy brochure is used.

PMID- 15963166
TI  - Racial and ethnic disparities in influenza vaccination among elderly adults.
AB  - OBJECTIVES: To examine whether access to care factors account for racial/ethnic
      disparities in influenza vaccination among elderly adults in the United States.
      DESIGN: Indicators of access to care (predisposing, enabling,
      environmental/system, and health need) derived from Andersen's behavioral model
      were identified in the National Health Interview Survey questionnaire. The
      relationship of these indicators to influenza vaccination and race/ethnicity was
      assessed with multiple logistic regression models. MAIN RESULTS: Significant
      differences in vaccination were observed between non-Hispanic (NH) whites (66%)
      and Hispanics (50%, P<.001) and between NH whites (66%) and NH blacks (46%,
      P<.001). Controlling for predisposing and enabling access to care indicators,
      education, marital status, regular source of care, and number of doctor visits,
      reduced the prevalence odds ratios (POR) comparing Hispanics to non-Hispanic
      whites from 1.89 to 1.27. For NH blacks, controlling for access to care
      indicators changed the POR only from 2.24 (95% CI, 1.9 to 2.7) to 1.93 (95% CI,
      1.6 to 2.4). CONCLUSIONS: This study confirmed the existence of sizable
      racial/ethnic differences in influenza vaccination among elderly adults. These
      disparities were only partially explained by differences in indicators of access
      to care, especially among non-Hispanic blacks for whom large disparities
      remained. Factors not available in the National Health Interview Survey, such as
      patient attitudes and provider performance, should be investigated as possible
      explanations for the racial/ethnic disparity in influenza vaccination among non
      Hispanic blacks.

PMID- 15963167
TI  - Poor patient comprehension of abnormal mammography results.
AB  - BACKGROUND: Screening mammography for women 50 to 69 years of age may lead to 50%
      having an abnormal study. We set out to determine the proportion of women who
      understand their abnormal mammogram results and the factors that predict
      understanding. METHODS: We surveyed 970 women age 40 to 80 years identified with
      abnormal mammograms from 4 clinical sites. We collected information on
      demographic factors, language of interview, consultation with a primary care
      physician, receipt of follow-up tests, and method of notification of index
      mammogram result. This study examines the following outcomes: the participant's
      report of understanding of her physician's explanation of results of the index
      mammogram, and a comparison of the radiology report to the participant's report
      of her index mammogram result. Multivariate models controlled for age, education,
      income, insurance status, and clinical site. RESULTS: The majority (70%) reported
      a "full understanding" of their physician's explanation of their abnormal
      mammogram, but a significant minority (30%) reported less than a full
      understanding (somewhat, not at all, did not explain). Among women of Asian
      ethnicity, only 63% reported full understanding. Asian ethnicity was a negative
      predictor (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3 to 0.7), and
      consultation with a primary care physician was a positive predictor (OR, 2.3; 95%
      CI, 1.7 to 3.3) of reported full understanding. Of the 304 women with a
      suspicious abnormality, only 51% understood their result to be abnormal. Women
      notified in person or by telephone were more likely than women notified in
      writing to understand their result to be abnormal (OR, 2.3; 95% CI, 1.2 to 4.8).
      CONCLUSION: Almost half of women with the most suspicious mammograms did not
      understand that their result was abnormal. Our data suggest that direct
      communication with a clinician in person or by phone improves comprehension.

PMID- 15963168
TI  - Recruiting ethnically diverse general internal medicine patients for a telephone
      survey on physician-patient communication.
AB  - BACKGROUND: Limited evidence exists on the effectiveness of recruitment methods
      among diverse populations. OBJECTIVE: Describe response rates by recruitment
      stage, ethnic-language group, and type of initial contact letter (for African
      American and Latino patients). DESIGN: Tracking of response status by recruitment
      stage and ethnic-language group and a randomized trial of ethnically tailored
      initial letters nested within a cross-sectional telephone survey on physician
      patient communication. PARTICIPANTS: Adult general medicine patients with >or=1
      visit during the preceding year, stratified by 4 categories: African-American (N=
      1,400), English-speaking Latino (N= 894), Spanish-speaking Latino (N= 965), and
      non-Latino white (N= 1,400). MEASUREMENTS AND RESULTS: Ethnically tailored
      initial letters referred to shortages of African-American (or Latino) physicians
      and the need to learn about the experiences of African-American (or Latino)
      patients communicating with physicians. Of 2,482 patients contacted, eligible,
      and able to participate (identified eligibles), 69.9% completed the survey.
      Thirty-nine percent of the sampling frame was unable to be contacted, with losses
      higher among non-Latino whites (46.5%) and African Americans (44.2%) than among
      English-speaking (32.3%) and Spanish-speaking Latinos (25.1%). For identified
      eligibles, response rates were highest among Spanish-speaking Latinos (75.2%),
      lowest for non-Latino whites (66.4%), and intermediate for African Americans
      (69.7%) and English-speaking Latinos (68.1%). There were no differences in
      overall response rates between patients receiving ethnically tailored letters
      (72.2%) and those receiving general letters (70.0%). CONCLUSIONS: Household
      contact and individual response rates differed by ethnic-language group,
      highlighting the importance of tracking losses by stage and subpopulation.
      Careful attention to recruitment yielded acceptable response rates among all
      groups.

PMID- 15963169
TI  - Brief report: if you build it, they will come: methods for recruiting Latinos
      into cancer research.
AB  - BACKGROUND: Latinos have low representation in cancer prevention trials and
      intervention studies. Culturally appropriate recruitment strategies are needed to
      address this issue. OBJECTIVE: To describe and summarize the effectiveness of
      recruitment strategies used by the Latin American Cancer Research Coalition
      (LACRC). DESIGN: Descriptive report of recruitment methods. PARTICIPANTS:
      Uninsured Latino immigrants (N=1,170; 77% female, 23% male) from Central and
      South America recruited to 7 cancer control studies. APPROACH: The LACRC
      recruitment model involved inclusion of Latino researchers and providers, and use
      of culturally acceptable materials released through culturally appropriate
      outlets such as Latino radio stations. RESULTS: The overall participation rate
      was high-96% of patients identified as eligible agreed to participate. Women were
      excellent referrals for recruiting men to research studies. Additionally, a local
      Latino radio program was used to efficiently recruit eligible study participants.
      CONCLUSIONS: Latinos are interested and willing to participate in cancer control
      studies when culturally relevant approaches are used. Research teams that partner
      with Latino researchers and with Latino service providers are important in
      educating Latinos about cancer control and encouraging participation in research.

PMID- 15963170
TI  - Populations at risk: a critical need for research, funding, and action.

PMID- 15963171
TI  - Medical education and JGIM.

PMID- 15963172
TI  - Functional status and patient satisfaction: a comparison of ischemic heart
      disease, obstructive lung disease, and diabetes mellitus.
AB  - OBJECTIVE: To determine the extent to which chronic illness and disease severity
      affect patient satisfaction with their primary care provider in general internal
      medicine clinics. DESIGN: Cross-sectional mailed questionnaire study. SETTING:
      Primary care clinics at 7 Veterans Affairs medical centers.
      PATIENTS/PARTICIPANTS: Of 62,487 patients participating in the Ambulatory Care
      Quality Improvement Project, 35,383 (57%) returned an initial screening
      questionnaire and were subsequently sent a satisfaction questionnaire. Patients
      (N=21,689; 61%) who returned the Seattle Outpatient Satisfaction Survey (SOSQ)
      were included in the final analysis, representing 34% of the original sample.
      MEASUREMENTS AND MAIN RESULTS: The organizational score of the SOSQ measures
      satisfaction with health care services in the internal medicine clinic, and the
      humanistic scale measures patient satisfaction with the communication skills and
      humanistic qualities of the primary care physician. For ischemic heart disease
      (IHD), chronic obstructive pulmonary disease (COPD), and diabetes, patient
      ability to cope with their disease was more strongly associated with patient
      satisfaction than disease severity. Among IHD patients, improvement in ability to
      cope emotionally with their angina was associated with higher SOSQ organizational
      scores (standardized beta=0.18; P<.001) but self-reported physical limitation due
      to angina was not (beta=0.01; P=.65). Similarly, in COPD, improved ability to
      cope with dyspnea was associated with greater organizational scores (beta=0.11;
      P<.001) but physical function was not (beta=-0.03; P=.27). For diabetes,
      increased education was associated with improved organizational scores
      (beta=0.31; P<.001) but improvement in symptom burden was not (beta=0.03; P=.14).
      Similar results were seen with prediction of SOSQ humanistic scores. CONCLUSIONS:
      Patient education and ability to cope with chronic conditions are more strongly
      associated with satisfaction with their primary care provider than disease
      severity. Further improvements in patient education and self-management may lead
      to improved satisfaction and quality of care.

PMID- 15963174
TI  - Causes of preventable visual loss in type 2 diabetes mellitus: an evaluation of
      suboptimally timed retinal photocoagulation.
AB  - To examine circumstances surrounding suboptimally timed retinal photocoagulation,
      we reviewed the medical records of 238 patients who had received photocoagulation
      for diabetic retinopathy at one of three large referral centers. Forty-three
      percent (95% confidence interval, 36% to 49%) of cases were rated as probably or
      definitely suboptimally timed (i.e., patient could have benefited from earlier
      photocoagulation). About one third of cases were due to patients going many years
      without screening (> 3 years), and two thirds were associated with surveillance
      problems (failures to achieve close follow-up for known retinopathy). We found
      that suboptimal timing of photocoagulation was common but was not due to patients
      going between 13 and 36 months between screening visits, suggesting that current
      performance measures, which focus on annual retinal examinations, may be
      requiring wasteful care while not addressing a major quality problem.

PMID- 15963173
TI  - Depression and glycemic control in Hispanic primary care patients with diabetes.
AB  - CONTEXT: Maintaining optimal glycemic control is an important goal of therapy in
      patients with diabetes mellitus. Patients of Hispanic ancestry have been shown to
      have high rates of diabetes and poor glycemic control (PGC). Although depression
      is common in adults with diabetes, its relationship to glycemic control remains
      unclear, especially among Hispanics. OBJECTIVE: To assess the association of
      depression with PGC in Hispanics. DESIGN: Data from a cross-sectional mental
      health survey in primary care were crosslinked to the hospital's computerized
      laboratory database. SETTING: Urban general medicine practice at a teaching
      hospital. PATIENTS: Two hundred and nine patients (mean [standard deviation] age,
      57.1 [10.3] years; 68% females) with recent International Classification of
      Diseases, Ninth Revision (ICD-9) codes for diabetes mellitus, and 1 or more
      hemoglobin A(1c) (HbA(1c)) tests. MAIN OUTCOME MEASURE: Probability of PGC
      (HbA(1c)>or=8%). RESULTS: Probability for PGC steadily increased with severity of
      depression. Thirty-nine (55.7%) of the 70 patients with major depression had
      HbA(1c)>or=8%, compared with 39/92 (42.4%) in the minimal to mild depression
      group, and 15/47 (31.9%) in the no depression group (P(trend)=.01; adjusted odds
      ratio, 3.27; 95% confidence interval, 1.23 to 8.64, for moderate or severe
      depression vs no depression). Only 29 (41.4%) of the patients with major
      depression received mental health treatment in the previous year. CONCLUSIONS: In
      this primary care sample of Hispanic patients with diabetes, we found a
      significant association between increasing depression severity and PGC. Yet, less
      than one half of the patients with moderate or severe depression received mental
      health treatment in the previous year. Improving identification and treatment of
      depression in this high-risk population might have favorable effects on diabetic
      outcomes.

PMID- 15963175
TI  - Internet use among primary care patients with type 2 diabetes: the generation and
      education gap.
AB  - BACKGROUND: The Internet represents a promising tool to improve diabetes care.
      OBJECTIVE: To assess differences in demographics, self-care behaviors, and
      diabetes-related risk factor control by frequency of Internet use. DESIGN AND
      PARTICIPANTS: We surveyed 909 patients with type 2 diabetes attending primary
      care clinics. MEASUREMENTS: Frequency of Internet use, socioeconomic status, and
      responses to the Problem Areas in Diabetes (PAID), Summary of Diabetes Self-care
      Activities (SDSCA), and Health Utilities Index (HUI) scales. Survey responses
      were linked to last measured hemoglobin A1c, cholesterol, and blood pressure
      results. Comorbidities and current medications were obtained from the medical
      record. RESULTS: Internet "never-users" (n=588, 66%) were significantly older
      (70.0+/-11.2 vs 59.0+/-11.3 years; P<.001) and less educated (26% vs 71%
      with>high school; P<.001) than Internet users (n=308, 34%). There were few
      significant differences in PAID or SDSCA scores or in diabetes metabolic control
      despite longer diabetes duration (10.3+/-8.2 vs 8.3+/-6.7 years; P<.001) and
      greater prevalence of coronary disease (40% vs 24%; P<.001) in nonusers. Less
      than 10% of current nonusers would use the Internet for secure health-related
      communication. CONCLUSIONS: Older and less educated diabetes patients are less
      likely to use the Internet. Despite greater comorbidity, nonusers engaged in
      primary care had equal or better risk factor control compared to users.

PMID- 15963176
TI  - Diabetes and cardiovascular disease among Asian Indians in the United States.
AB  - CONTEXT: Studies, mostly from outside the United States, have found high
      prevalence of diabetes, coronary heart disease (CHD), and hypertension among
      Asian Indians, despite low rates of associated risk factors. OBJECTIVE: To
      analyze the prevalence of obesity, diabetes, CHD, hypertension, and other
      associated risk factors among Asian Indians in the United States compared to non
      Hispanic whites. DESIGN, SETTING, AND SUBJECTS: Cross-sectional study using data
      from the National Health Interview Survey (NHIS) for 1997, 1998, 1999, and 2000.
      We analyzed 87,846 non-Hispanic whites and 555 Asian Indians. MAIN OUTCOME
      MEASURES: Whether a subject reported having diabetes, CHD, or hypertension.
      RESULTS: Asian Indians had lower average body mass indices (BMIs) than non
      Hispanic whites and lower rates of tobacco use, but were less physically active.
      In multivariate analysis controlling for age and BMI, Asian Indians had
      significantly higher odds of borderline or overt diabetes (adjusted OR [AOR],
      2.70; 95% confidence interval [CI], 1.72 to 4.23). Multivariate analysis also
      showed that Asian Indians had nonsignificantly lower odds ratios for CHD (AOR,
      0.58; 95% CI, 0.25 to 1.35) and significantly lower odds of reporting
      hypertension (AOR, 0.58; 95% CI, 0.42 to 0.82) compared to non-Hispanic whites.
      CONCLUSION: Asian Indians in the United States have higher odds of being diabetic
      despite lower rates of obesity. Unlike studies on Asian Indians in India and the
      United Kingdom, we found no evidence of an elevated risk of CHD or hypertension.
      We need more reliable national data on Asian Indians to understand their
      particular health behaviors and cardiovascular risks. Research and preventive
      efforts should focus on reducing diabetes among Asian Indians.

PMID- 15963177
TI  - Brief report: the burden of diabetes therapy: implications for the design of
      effective patient-centered treatment regimens.
AB  - BACKGROUND: Management of diabetes, and in particular blood glucose, can be
      complex and burdensome. OBJECTIVE: To evaluate patient views of the burdens of
      therapy and its impact on self-management. PATIENTS: Veteran patients with type 2
      diabetes. DESIGN: Mailed survey. MEASUREMENTS: Patients described their views of
      the burden of diabetes treatments, adherence, and clinical and demographic
      status. Factors associated with ratings of burden and adherence to therapy were
      examined using multivariate regression methods. RESULTS: The response rate was
      67% (n=1,653). Patients viewed pills as the least burdensome treatment and
      insulin as the most burdensome. Ratings of the burden of insulin were lower if a
      patient had prior experience with therapy. Adherence to prescribed therapy varied
      substantially; for example, patients followed medication recommendations more
      closely than other areas of self-management. Multivariate analyses showed that
      the main predictor of adherence was patients' ratings of the burden of therapy.
      CONCLUSIONS: Injected insulin regimens are viewed as highly burdensome by
      patients, although this burden is attenuated by experience. Adherence to self
      management is strongly and independently correlated with views of treatment
      burden. The burden of diabetes-related treatments may be a source of suboptimal
      glucose control seen in many care settings. Providers should consider the burden
      of treatment for a particular patient and its impact on adherence as part of a
      decision-making process to design effective treatment regimens.

PMID- 15963178
TI  - Time for "drilling down".

PMID- 15963181
TI  - Conceptualizing in nursing: what's the point?

PMID- 15963180
TI  - Caring for older Americans: the future of geriatric medicine.
AB  - In response to the needs and demands of an aging population, geriatric medicine
      has grown rapidly during the past 3 decades. The discipline has defined its core
      values as well as the knowledge base and clinical skills needed to improve the
      health, functioning, and well-being of older persons and to provide appropriate
      palliative care. Geriatric medicine has developed new models of care, advanced
      the treatment of common geriatric conditions, and advocated for the health and
      health care of older persons. Nevertheless, at the beginning of the 21st century,
      the health care of older persons is at a crossroads. Despite the substantial
      progress that geriatric medicine has made, much more remains to be done to meet
      the healthcare needs of our aging population. The clinical, educational, and
      research approaches of the 20th century are unable to keep pace and require major
      revisions. Maintaining the status quo will mean falling further and further
      behind. The healthcare delivery and financing systems need fundamental redesign
      to improve quality and eliminate waste. The American Geriatrics Society (AGS)
      Task Force on the Future of Geriatric Medicine has identified five goals aimed at
      optimizing the health of older persons: To ensure that every older person
      receives high-quality, patient-centered health care; To expand the geriatrics
      knowledge base; To increase the number of healthcare professionals who employ the
      principles of geriatric medicine in caring for older persons; To recruit
      physicians and other healthcare professionals into careers in geriatric medicine;
      To unite professional and lay groups in the effort to influence public policy to
      continually improve the health and health care of seniors. Geriatric medicine
      cannot accomplish these goals alone. Accordingly, the Task Force has articulated
      a set of recommendations primarily aimed at the government, organizations,
      agencies, foundations, and other partners whose collaboration will be essential
      in accomplishing these goals. The vision described in this document and the
      accompanying recommendations are only the broad outline of an agenda for the
      future. Geriatric medicine, through its professional organizations and its
      partners, will need to mobilize resources to identify and implement the specific
      steps that will make the vision a reality. Doing so will require broad
      participation, consensus building, creativity, and perseverance. The consequences
      of inaction will be profound. The combination of a burgeoning number of older
      persons and an inadequately prepared, poorly organized physician workforce is a
      recipe for expensive, fragmented health care that does not meet the needs of our
      older population. By virtue of their unique skills and advocacy for the health of
      older persons, geriatricians can be key leaders of change to achieve the goals of
      geriatric medicine and optimize the health of our aging population. Nevertheless,
      the goals of geriatric medicine will be accomplished only if geriatricians and
      their partners work in a system that is designed to provide high-quality,
      efficient care and recognizes the value of geriatrics.

PMID- 15963182
TI  - Patient management of long-term continuous subcutaneous insulin infusion.
AB  - AIM: This paper reports a study of patients' current practice with continuous
      subcutaneous insulin infusions, particularly with respect to the management of
      the pump. BACKGROUND: Successful implementation of continuous subcutaneous
      insulin infusion requires a motivated patient with a range of technical skills
      and self-management capabilities. The therapy should be prescribed, implemented
      and monitored by a skilled professional team familiar with it and capable of
      supporting the patient. METHODS: A questionnaire was mailed to 102 continuous
      subcutaneous insulin infusion treated patients at a Swedish university hospital
      with experience of pump treatment for at least 6 months. RESULTS: The
      questionnaire was answered by 88% of the patients, 53 women and 37 men, aged 22
      71 years with a duration of continuous subcutaneous insulin infusion use of
      between 7 months and 19 years. The changing interval for soft infusion set ranged
      from 2.0 to 10.0 days (mean 4.8) and for metal needles from 1.5 to 7.5 days (mean
      3.8), P = 0.001. Catheter occlusions were significantly more often reported in
      patients with presence of bleeding at the infusion site (P = 0.011) and among
      those using insulin lispro (P = 0.032). CONCLUSIONS: Patients having long-term
      continuous subcutaneous insulin infusion should be carefully audited with respect
      to the management of the insulin pump and its accessories. In patients who
      frequently experience problems, shorter intervals between changes of infusion
      sets are strongly advocated and type of insulin preparation may be of importance
      in some cases.

PMID- 15963183
TI  - Self-care strategies for depressive symptoms in people with HIV disease.
AB  - AIM: This paper reports a study with people living with HIV to examine the
      experience of depressive symptoms, self-care symptom management strategies,
      symptom outcomes in response to those strategies, and sources from which the
      strategies were learned. BACKGROUND: Depressive symptoms are common, under
      diagnosed and under-treated in people living with HIV. These symptoms have been
      associated with lower medication adherence, risky behaviours and poorer health
      outcomes. METHODS: The study was based on the model of symptom management
      developed by the University of California San Francisco School of Nursing Symptom
      Management Faculty. Thirty-four HIV+ men and women from a larger study of symptom
      self-care strategies (n = 422) reported experiencing depressive symptoms. Data
      were collected from this subset on the Web, by mail and in-person using the
      critical incident technique. RESULTS: Depressive symptoms were described using 80
      words and phrases clustered into eight categories: futility, sadness,
      loneliness/isolation, fatigue, fear/worry, lack of motivation, suicidal thoughts
      and other. A total of 111 self-care strategies were coded into six categories:
      practising complementary/alternative therapies, talking to others, using
      distraction techniques, using antidepressants, engaging in physical activity, and
      using denial/avoidant coping. Sources of information for strategies used were
      trial and error (31%), healthcare providers (28%), family and friends (20%),
      classes/reading (8%), clergy (8%), support groups (4%) and other (3%). Overall,
      92% of the self-care strategies used were reported as helpful, 4% were sometimes
      helpful and 4% were not helpful. CONCLUSIONS: People living with HIV use numerous
      effective self-care strategies to manage depressive symptoms. Further study is
      needed to validate the use of these strategies across populations, to standardize
      dose, duration and frequency, and to measure their effectiveness.

PMID- 15963184
TI  - Community nurses' talk of equality and the discursive constitution of selves.
AB  - AIM: The aim of this paper is to explore how stories revealed the discursive
      constitution of particular selves and to consider the implications for future
      understandings of equality and practice. BACKGROUND: Equality has long been an
      objective of most Western healthcare systems, as enshrined in the principles of
      equal rights to access, treatment and care. Service users, however, continue to
      experience inequities, oppression and discrimination. These continuing
      inequalities have resulted in demands for nurses to tackle discrimination and
      oppression and promote equality in their practice. METHODS: Semi-structured
      interviews were conducted with 14 community nurse students and 14 practice
      teachers from two universities in England in 1998. Discourse analysis was used to
      interpret the narratives. FINDINGS: Community nurses were actively positioning
      themselves and were being positioned through dominant and competing discourses.
      Their narratives revealed stories of equality in health care that were contingent
      upon complex discursively constituted selves. They were found to take up, rework
      and in some cases subvert and reject dominant subject positions. The implications
      of these selves are considered in relation to the development of equality and
      practice. CONCLUSIONS: Educationalists and practitioners need to engage with
      these discourses and diverse selves and begin to develop approaches which remain
      open to scrutiny and challenge so that specific and localized understandings of
      equality and practice can evolve.

PMID- 15963185
TI  - Patients' and nurses' perceptions of nursing problems in an acute care setting.
AB  - AIM: This paper reports a study to determine the degree of agreement or
      disagreement between nurses and patients in their perceptions of the presence,
      severity, and importance of nursing problems. BACKGROUND: Patient experiences,
      values and preferences are increasingly acknowledged as important factors
      underpinning healthcare decision-making. The ability to identify patient problems
      accurately is an important prerequisite for planning and implementing
      individualized high quality care. METHODS: A convenience sample of patients (n =
      80) and Registered Nurses (n = 30) in an acute care setting responded to a 43
      item questionnaire. Findings. Nurses identified patients' problems with a
      sensitivity of 0.53 and a positive predictive value of 0.50. Patients identified
      several severe problems that were not identified by nurses, particularly problems
      with nutrition, sleep, pain, and emotions/spirituality. Nurses underestimated the
      severity in 47% of mutually-identified problems. An overall level of agreement of
      44% was found on the importance of patient problems. Low levels of agreement on
      severity and importance were related more to individual differences than to
      systematic differences. CONCLUSIONS: Nurses need to be more aware that patients
      and nurses often hold disparate views of the priorities in nursing care. To plan
      individualized nursing care effectively, nurses need to elicit and use individual
      patients' preferences more systematically in care planning.

PMID- 15963186
TI  - Effects of Sun-style Tai Chi exercise on physical fitness and fall prevention in
      fall-prone older adults.
AB  - AIM: This paper reports a study to determine changes in the physical fitness
      (knee and ankle muscle strength, balance, flexibility, and mobility), fall
      avoidance efficacy, and fall episodes of institutionalized older adults after
      participating in a 12-week Sun-style Tai Chi exercise programme. BACKGROUND: Fall
      prevention has a high priority in health promotion for older people because a
      fall is associated with serious morbidity in this population. Regular exercise is
      effective in fall prevention for older adults because of improvements in strength
      and balance. Tai Chi exercise is considered to offer great potential for health
      promotion and rehabilitation, particularly in the maintenance of good mental and
      physical condition in older people. METHODS: A quasi-experimental design with a
      non-equivalent control group was used. Data were collected from September 2001 to
      January 2002. A total of 68 fall-prone older adults with a mean age of 77.8 years
      participated in the study, and 29 people in the Tai Chi group and 30 controls
      completed the post-test measures. The Tai Chi exercise programme was provided
      three times a week for 12 weeks in the experimental group. Data were analysed for
      group differences using t-tests. RESULTS: At post-test, the experimental group
      showed significantly improved muscle strength in knee and ankle flexors (P <
      0.001) and extensors (P < 0.01), and improved flexibility (P < 0.01) and mobility
      (P < 0.001) compared with the control group. There was no significant group
      difference in fall episodes, but the relative risk ratio for the Tai Chi exercise
      group compared with the control group was 0.62. The experimental group reported
      significantly more confidence in fall avoidance than did the control group.
      CONCLUSION: The findings reveal that Tai Chi exercise programmes can safely
      improve physical strength and reduce fall risk for fall-prone older adults in
      residential care facilities.

PMID- 15963187
TI  - Predictors of distress and depression in elders with arthritic pain.
AB  - AIM: The aim of this paper is to report the findings of a study testing a theory
      of chronic pain, with financial hardship added as a contextual stimulus.
      BACKGROUND: Arthritis is highly prevalent among older people, resulting in severe
      pain and suffering. A previous study testing a theory of chronic pain in elders
      with arthritis found that pain, disability and social support explained only 35%
      of the variance in their emotional distress. It is possible that demands, other
      than chronic pain, such as financial hardship, also contribute to these elders'
      stress and depression. METHOD: The theory was tested with 235 elders with
      arthritis using a secondary data analysis strategy. Data were obtained from the
      study of Ageing, Status, and Sense of Control carried out in 1998 in the United
      States of America. Variables were constructed from original questionnaires.
      RESULTS: The hypothesized model fitted the data only moderately well (chi2 =
      40.04, d.f = 6, P < 0.0001; CFI = 0.88; NFI = 0.88). Disability and financial
      hardship positively predicted distress, while social support and age had a
      reverse impact on distress, which explained 24% of the variance in distress. This
      means that elders with higher levels of disability, more financial hardship, less
      social support or younger age are likely to have higher levels of distress.
      Distress alone explained 33% of the variance in depressive symptoms. A data
      derived model was created with excellent fit (chi2 = 3; d.f. = 4; P = 0.56; CFI =
      1.00; NFI = 0.99), showing that disability, social support, financial hardship
      and age predicted distress (R2 = 0.24). Pain, disability and distress predicted
      depression (R2 = 0.44). CONCLUSIONS: The results partially supported the theory.
      Exploring the possibility of using depression as part of the control process and
      removing gender as a residual stimulus may lead to further refinement of the
      theory. The findings allow nurses to have a better understanding of the
      experiences of elders with arthritis, and thus to offer appropriate care to meet
      their needs.

PMID- 15963188
TI  - Older people's willingness to use home care nursing services.
AB  - AIM: This paper reports a study exploring willingness to use home care nursing
      services among older people and discussing the implications for long-term and
      home care nursing policies. BACKGROUND: The proportion of older people is
      increasing in all societies across the world. Correspondingly, Korean society has
      experienced a rapid growth in its population of older people, and this is
      expected to increase from 7.2% in 2000 to 14.4% in 2019. The government is in the
      process of developing publicly-financed long-term care for older people, and home
      care nursing services are expected to be provided as an element of this care.
      Methods. A cross-sectional study design was used, employing data from a
      nationally representative interview survey with 1834 respondents conducted during
      May and July, 2001. Univariate and logistic regression analyses were conducted.
      RESULTS: Willingness to use home care nursing services differed according to
      whether co-payment was required. About half the respondents answered that they
      would not use the services; 43% expressed a willingness to use them without co
      payment; and 5% were very willing to use them even with co-payment. People with
      lower incomes showed greater willingness to use the services with no co-payment,
      while the high income group showed the greatest willingness under co-payment.
      Sex, living with adult children, living area, activities of daily living, and
      chronic conditions were associated with willingness. Older people who had known
      about or used home care nursing services previously showed greater willingness.
      CONCLUSIONS: Co-payment guidelines for minimizing unmet needs are required,
      especially for older people with low incomes. A positive evaluation from those
      who knew about or had used such services is expected to contribute to the use of
      home care nursing services by older people.

PMID- 15963189
TI  - Developing and validating a tool to measure parenting self-efficacy.
AB  - AIMS: This paper reports the development of a tool to measure parenting self
      efficacy as an aid to evaluating parenting programmes. BACKGROUND: Whilst there
      has been increasing interest in parenting programmes from parents, government and
      professionals, there is a lack of rigorous evaluation studies of their
      effectiveness, particularly their longer-term outcomes. Equally, there is little
      research evidence of the views and experiences of parents themselves. It is
      important to develop robust outcome measures which draw on well-developed
      theoretical constructs to measure parents' perceived abilities to manage their
      children based on their own views and experiences. Self-efficacy, a self
      perception of one's ability to perform competently and effectively in a
      particular task or setting, may provide such a framework. METHODS: Data from 12
      focus groups conducted with parents and parenting programme facilitators informed
      the development of the tool. A thematic analysis of the focus group transcripts
      identified key items to be included in the self-efficacy instrument, and these
      were developed into 82 Likert-format statements. A multi-method approach was used
      to test the instrument for validity and reliability. FINDINGS: Nine domain
      specific sub-scales of parenting were identified from the analysis of the focus
      group data. Internal reliability coefficients for the subscales ranged from 0.80
      to 0.89, and the overall scale reliability was 0.94. External reliability
      coefficients ranged from rs = 0.58 (n = 19, P < 0.01) to rs = 0.88 (n = 19, P <
      0.01). CONCLUSION: A valid and reliable tool to measure parenting self-efficacy
      has been developed, which will aid evaluation of parenting programmes.

PMID- 15963190
TI  - Using concept maps to optimize the composition of collaborative student groups: a
      pilot study.
AB  - AIM: The aim of this paper is to stimulate interest in the practical classroom
      application of concept mapping strategies as an approach that teachers can easily
      use to enhance collaborative learning. BACKGROUND: Concept mapping has been
      developed as a tool to support meaningful learning. However, much of the research
      literature fails to explain how concept maps might be most gainfully employed
      within the classroom. As a result, concept mapping is a tool that is under-used.
      METHODS: Students on a postgraduate teacher preparation programme for nurses were
      arranged in triads on the basis of the morphology of individually-produced
      concept maps for the topics of 'genetics' and 'pathogenic microbes'. They were
      arranged in heterogeneous triads to produce a consensus map for 'pathogenic
      microbes', and then in homogeneous triads to produce a consensus map for
      'genetics'. The number of acceptable propositions found in their individual maps
      was compared with the number found in the consensus group maps, and gain scores
      were calculated for each participant. FINDINGS: Participants arranged in triads
      of individuals having very different knowledge structures were found to make a
      greater improvement than those arranged in triads composed of individuals with
      qualitatively similar knowledge structures. CONCLUSIONS: The study was undertaken
      with a very small sample and only looked at two topic areas. However, the
      findings support the idea that collaborative groups work most effectively when
      individuals within the group bring different perspectives to a problem, and that
      this perspective can be usefully identified within the classroom environment as
      variations in concept map morphology.

PMID- 15963191
TI  - Nurses' views on ethical codes: a focus group study.
AB  - AIM: This paper reports a study exploring nurses' views on the 'potential'
      content and functions of an ethical code for nurses in Belgium. The term
      'potential' is used, because Belgian nurses do not have experience with an
      ethical code. BACKGROUND: Ethical codes have been developed to guide nurses'
      practice and to improve their professional status. Little empirical research,
      however, has been undertaken to determine nurses' views on the content and
      functions of these codes. The available quantitative studies merely give some
      information on nurses' (lack of) knowledge and use of their ethical code. No
      nursing ethical code currently exists in Belgium. Qualitative research exploring
      nurses' views, therefore, was needed in order to find out which functions an
      ethical code could fulfil and what the code's content could be. METHOD: Eight
      focus groups were conducted with 50 nurses in different healthcare settings in
      Belgium. Data were generated during 2003. FINDINGS: According to participants, an
      ethical code could fulfil several functions, including supporting their
      professional nursing identity (external function) and giving guidelines for
      nursing practice (internal function). In addition, some aspects of content were
      mentioned, including nurses' responsibilities in a relational context: particular
      attention should be paid to the personality of the nurse and to the specificity
      of nursing as a relational activity. Most agreement was reached on the 'ethical'
      function of the code, namely guiding nurses' professional moral practice.
      Regarding disciplinary use and the need for legalization of the ethical code, on
      the contrary, opinions were divergent. CONCLUSIONS: It is of utmost importance to
      take into account nurses' views when developing an ethical code for their
      profession. This study gave a first picture of the views of nurses themselves.
      These initial findings should be completed with nurses' views on the formulation,
      dissemination and promotion of the ethical code. Such evidence-based development
      of an ethical code will probably give more guarantees that the code will meet
      nurses' expectations and will function optimally.

PMID- 15963195
TI  - Blood pressure and cardiovascular risk reduction--new targets, new challenges.

PMID- 15963197
TI  - Effects of sibutramine in overweight, poorly controlled Chinese female type 2
      diabetic patients: a randomised, double-blind, placebo-controlled study.
AB  - To assess the efficacy of sibutramine 15 mg once daily as weight reduction in
      overweight and obese (body mass index > 25 kg/m2) Chinese female type 2 diabetic
      patients and to evaluate the influence of weight loss on diabetic control, a
      randomised, double-blind, placebo-control, 12-week study was conducted. Chinese
      female type 2 diabetic patients, poorly controlled glucose levels and HbA(1C) >
      8% were randomly assigned to two groups. In addition to their hypoglycaemic
      agents (maximal doses of sulphonylureas and metformin), one group (n = 30)
      received a sibutramine 15 mg once daily for 12 weeks, and the other (n = 30)
      received placebo for the same period. Comparing the changes that occurred after
      12 weeks in the sibutramine and placebo groups, the former showed significantly
      greater reduction in body weight (2.5 vs. 0.1 kg, p < 0.05), fasting plasma
      insulin level (28.8 vs. 2.4 pmol/l, p < 0.01), 2-h postprandial blood glucose
      after standard test meal (3.2 vs. 1.1 mmol/l, p < 0.01), insulin resistance (5.1
      vs. 0.2, p < 0.01), HbA1C (1.7% vs. 0.2%, p < 0.05), triglyceride (0.43 vs. 0.12
      mmol/l, p < 0.05) and total cholesterol (0.52 vs. 0.08 mmol/l, p < 0.05). No
      significant differences were found between treatment groups in blood pressure and
      heart rate. The addition of sibutramine to diet and oral hypoglycaemic therapy
      resulted in significant weight loss and improvement in metabolic parameters in
      the treatment group. Sibutramine should be considered for use alongside diet and
      oral hypoglycaemic therapy in Chinese overweight and obese women with poorly
      controlled type 2 diabetes.

PMID- 15963198
TI  - Short burst oxygen therapy in chronic obstructive pulmonary disease: a patient
      survey and cost analysis.
AB  - The prescription of home oxygen cylinders is substantial. This study aimed to
      establish patient's current use of short burst oxygen therapy in chronic
      obstructive pulmonary disease (COPD) and to examine potential cost savings if
      cylinder use had been replaced by a concentrator. An interviewer-administered
      questionnaire was completed by 100 patients currently receiving short burst
      oxygen therapy. Patients reported that they used their oxygen before
      exercise/activity (26%), during exercise (19%), after exercise/activity (87%) and
      at rest (46%) and mostly for the relief of symptomatic breathlessness. The length
      of time [mean (SD)] patients had oxygen at home was 27.42 (29.31) months. Of
      those patients using cylinders, savings could have been made by transferring from
      cylinders to concentrators. While withdrawal of oxygen may be difficult, an
      oxygen assessment service could ensure that future prescription is aimed at those
      who benefit and is delivered by the most cost-effective method.

PMID- 15963199
TI  - Efficacy and safety of salmeterol/fluticasone propionate delivered via a
      hydrofluoroalkane metered dose inhaler in Chinese patients with moderate asthma
      poorly controlled with inhaled corticosteroids.
AB  - A randomised, open-label, multicentre study compared the efficacy and
      tolerability of salmeterol 25 microg/fluticasone propionate 125 microg (two
      puffs, twice daily) delivered via a hydrofluoroalkane metered-dose inhaler (HFA
      MDI) and salmeterol 50microg/fluticasone propionate 250 microg (one puff, twice
      daily) delivered via a Diskus inhaler in Chinese patients with moderate asthma
      uncontrolled with inhaled corticosteroids (ICSs). Morning peak expiratory flow
      (PEF) was the primary efficacy endpoint. Secondary endpoints included evening
      PEF, forced expiratory volume in 1 s, day and night symptom scores, rescue
      medication and patient self-evaluation of efficacy. Safety was assessed according
      to adverse events recorded. Both treatments were equipotent and significantly
      improved morning PEF (HFA-MDI 40 l/min; Diskus 42 l/min; p < 0.05) and all
      secondary endpoints (p < 0.05) from baseline, over 1-4 weeks. Similarly, both
      treatments were well tolerated. Salmeterol/fluticasone propionate delivered via
      an HFA-MDI or Diskus inhaler provides a choice of efficacious delivery systems in
      Chinese patients whose asthma is poorly controlled on ICSs alone.

PMID- 15963200
TI  - Pain-relieving factors in migraine and tension-type headache.
AB  - We performed the present study to compare patients with migraine and tension-type
      headache (TTH) in their behaviour during the attacks and the manoeuvres to
      relieve the pain. One hundred thirty consecutive patients with either migraine (n
      = 75) or TTH (n = 55) were questioned (including the use of a checklist)
      concerning their usual behaviour during the attacks and non-pharmacological
      manoeuvres performed to relieve the pain. The results of the two types of
      headache were compared. Patients with migraine tended to perform more manoeuvres
      than patients with TTH (mean: 4.3 vs. 3.6). These manoeuvres included pressing
      and applying cold stimuli to the painful site, trying to sleep, changing posture,
      sitting or reclining in bed (using more pillows than usual to lay down),
      isolating themselves, using symptomatic medication, inducing vomiting, changing
      diet and becoming immobile during the attacks. The only measure predominantly
      reported by patients with TTH was scalp massage. Migraineurs, compared to
      patients with TTH, changing eating habits, pressed the pain site; there were no
      significant differences between the two groups. The behaviour of patients during
      headache attacks varies with the diagnosis. Measures that do not always result in
      pain relief are performed in order to prevent its worsening or to improve
      associated symptoms. These behavioural differences may be because of the
      different pathogenesis of the attacks or of various styles of dealing with the
      pain. They can also aid the differential diagnosis between headaches in doubtful
      cases.

PMID- 15963201
TI  - Assessment of efficacy and psychomotor performances of thiocolchicoside and
      tizanidine in patients with acute low back pain.
AB  - Objectives of this study were to assess efficacy and effects on psychomotor
      performances of thiocolchicoside (TCC) and tizanidine (TZ) compared to placebo.
      Patients complaining of acute low back pain (LBP) associated with muscle spasm
      were enrolled in this randomised, double-blind clinical trial, comparing the
      effects of oral TCC, TZ and placebo on psychomotor performances assessed by a
      visual analogue scale of tiredness, drowsiness, dizziness and alertness and by
      psychometric tests after 2 and 5-7 days of treatment. The efficacy assessments,
      both TCC and TZ, were more effective than placebo in improving pain at rest, hand
      to-floor distance, Schober test and decreased paracetamol consumption. There were
      significant differences among the treatment groups in favour of TCC compared to
      TZ in visual analog scale-parameters. TZ-induced reduction of psychomotor
      performances of the patients was confirmed by psychometric tests, which showed
      significant differences among groups. This study showed that TCC is at least as
      effective as TZ in the treatment of acute LBP, while it appears devoid of any
      sedative effect in contrast to TZ.

PMID- 15963202
TI  - The comparison of two lower extremity block techniques combined with sciatic
      block: 3-in-1 femoral block vs. psoas compartment block.
AB  - The objective of this study was to compare clinical and postoperative analgesic
      effects of femoral or psoas compartment blocks in patients undergoing
      arthroscopies. Fifty patients were randomly assigned to one of the two groups.
      Either femoral (group F) or psoas compartment (group P) block was applied
      followed by sciatic nerve block. All nerve blocks were provided with a 15 ml of
      bupivacaine 0.5% + 10 ml of lignocaine (lidocaine) 2%. Systolic and diastolic
      blood pressure (SBP and DBP), heart rate, and pulse oxymetry (SpO2) were
      recorded. Quality of anaesthesia, time to first analgesic use, verbal pain scores
      (VPS), sensorial and motor blockade resolution times and side effects were also
      recorded. Quality of anaesthesia, complete sensory blockade of obturator and
      lateral cutaneous nerves were higher in the group P than in group F. However,
      complete motor blockade findings were similar in both groups. In the group P, VPS
      values measured at 10 and 15 min were lower than that of group F. These values
      decreased at 10 min and thereafter as to baseline values. VPS values of the group
      F declined at 20 min and following measurement times as to baseline values.
      Durations of motor and sensorial block, and time to first analgesic use were
      similar between two groups. Total analgesic consumption at first 24 h in group P
      was lower than those of group F. Regarding heart rates, SpO2, SBP and DBP values,
      no significant differences were found between the groups. Combined psoas-sciatic
      technique provided more comfortable intraoperative anaesthesia and better
      postoperative analgesia when compared with femoral-sciatic technique for
      arthroscopic procedures.

PMID- 15963203
TI  - Impaired endothelium-dependent flow-mediated dilation in Behcet's disease: more
      prominent endothelial dysfunction in patients with vascular involvement.
AB  - Brachial artery endothelial dysfunction was shown previously in a small group of
      Behcet's disease (BD) patients. This study aimed to compare the endothelial
      function in BD patients with and without vascular involvement. The study group
      consisted of 25 BD patients with vascular involvement, 25 BD patients without any
      vascular disease and 46 healthy controls. Brachial artery flow-mediated
      (endothelium-dependent) dilation (FMD), nitroglycerine-induced dilation and
      carotid artery intima-media thickness were measured. FMD was impaired in patients
      with BD (10.41 +/- 3.85%) compared to healthy controls (14.41 +/- 3.39%, p <
      0.001). FMD was significantly lower in BD patients with vascular involvement
      (8.80 +/- 3.63%) than those without any vascular disease (12.02 +/- 3.43%, p =
      0.003). This study reveals that endothelial dysfunction documented by brachial
      artery FMD is a feature of BD, and it is more prominent in patients with vascular
      involvement.

PMID- 15963204
TI  - Thrombocytopenia due to hypotension unrelated to infection: shock marrow.
AB  - Although peripheral blood cytopenias are observed in clinical practice following
      hypotensive episodes unrelated to infection, there has previously been no formal
      description of this in the medical literature. We retrospectively reviewed all
      medical intensive care unit records from two hospitals over a 5-year period to
      identify cases in which sustained hypotension had occurred that was unrelated to
      infection. After initial review, 10 records were identified that met our criteria
      (systolic blood pressure < 90 mmHg for at least 6 h, with no evidence of sepsis
      or use of drugs commonly associated with suppression of haematopoiesis). All 10
      of these patients were found to develop thrombocytopenia. The degree of
      thrombocytopenia correlated with the severity and duration of hypotension. Severe
      thrombocytopenia appeared to be associated with a poor outcome. Thrombocytopenia
      following shock unrelated to sepsis is common and is presumably related to
      hypoxic injury to haematopoietic progenitor cells.

PMID- 15963205
TI  - Anticardiolipin antibody and Taiwanese chronic haemodialysis patients with
      recurrent vascular access thrombosis.
AB  - Vascular access failure is a major cause of morbidity in chronic haemodialysis
      (HD) patients. However, some factors (such as homocysteine levels) are known
      regarding the risk factors predisposing certain HD patients to vascular access
      thrombosis (VAT). Immunoglobulin-G anticardiolipin antibody (IgG-ACA) is strongly
      associated with venous and arterial thrombosis in patients with normal renal
      function. Previous investigations have reported the characteristics of patients
      with raised IgG-ACA titre and recurrent VAT of HD in Western countries, but few
      equivalent studies exist for Taiwan. This retrospective study attempts to
      determine whether raised IgG-ACA titres are associated with an increased risk of
      recurrent VAT in chronic HD patients. This study enrolled 483 patients undergoing
      HD. IgG-ACA titre and hepatitis B&C marker were measured for all patients. A
      history of recurrent (VAT more than one) and/or VAT was elicited by using
      information from the patient questionnaires and was verified by means of careful
      inpatient and outpatient chart review. Raised IgG-ACA titres were present in
      21.7% (105/483) of patients. In both groups (raised IgG-ACA and normal IgG-ACA),
      the type of shunt differed significantly (p = 0.029). In predicting for more or
      one episodes of VAT by using multiple logistic regression with all significant
      factors, synthetic graft was also a significant factor (p < 0.0001). The 105
      raised IgG-ACA titres and 378 normal IgG-ACA titres were associated between
      chronic HD patients and recurrent VAT (p = 0.034). In predicting for more or one
      episode of VAT by using multiple logistic regression with all significant
      factors, raised IgG-ACA titre was a non-significant factor (p = 0.336). The
      presence of hepatitis C had a higher percentage in group with raised IgG-ACA
      titres of HD patients (p = 0.042). In predicting for more or one episode of VAT
      by using multiple logistic regression with all significant factors, the presence
      of hepatitis C was also a significant factor (p = 0.022). In conclusion, the
      prevalence of raised IgG-ACA titres was 21.7% among HD patients. There was a weak
      association between raised IgG-ACA titre and recurrent VAT and this finding may
      be the consequence of pathogenetic role of raised IgG-ACA titres in the
      development of VAT status for chronic HD patients. The presence of hepatitis C
      was a cofactor.

PMID- 15963206
TI  - Histopathological features of liver and its relation to serum transaminase levels
      in 91 cases of anti-HBe-positive chronic hepatitis B.
AB  - For assessing the histopathological features and its relation to alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels in anti-HBe
      positive chronic hepatitis B in Babol, north of Iran, liver biopsy samples of 91
      anti-HBe-positive chronic hepatitis B virus (HBV) infection with raised ALT were
      scored according to histological hepatitis activity index (HAI) from March 2000
      to July 2003. Seventy-seven males and 14 females with a mean age of 32.24 (+/
      11.92) years were studied. Mean ALT and AST levels were 112.5 (+/-98.9) and 69.57
      (+/-60.6) IU/l, respectively. Minimal, mild, moderate and severe chronic
      hepatitis were seen in 35 (38.5%), 49 (53.8%), seven (7.7%) and 0 cases,
      respectively. There was not any significant difference between HAI and ALT levels
      of < 60, between 60-79 and > or = 80 IU/l (p = 0.299), but with regard to AST
      levels, this difference was significant (p = 0.005). This study showed that more
      than 90% of our cases are in the early stages of the liver disease. Although both
      serum ALT and AST levels are associated with the activity of hepatitis in HBV
      carriers, the AST is a better laboratory screening test for finding the severity
      of liver injury than ALT.

PMID- 15963207
TI  - The prevalence of benign breast disease in women with polycystic ovary syndrome:
      a review of a 12-year follow-up.
AB  - A cross-sectional study of benign breast disease (BBD) was conducted to determine
      the actual prevalence and follow-up importance of BBD among women with polycystic
      ovary syndrome (PCOS) in conjunction with an ongoing prospective cohort study.
      The present study involved a subset of the original group of 244 women with a
      diagnosis of PCOS and 244 control women matched by age and race. A total of 240
      women (116 cases and 124 controls) were included in the present analysis. The
      majority of women in each group were Caucasians (93 and 96%, respectively). The
      median age was 46 years in the cases and 47 years in the controls. Screening
      mammography begins at the age of 40 and has been carried out in 69% of cases and
      66% of controls since the study began. Family history of breast disease was
      observed in 27 cases of both the groups (p > 0.05). Neither fibrocystic breast
      disease, lump thickening, calcification, fibroadenoma, pain, redness, discharge
      nor hyperplasia showed a significantly higher prevalence rate in cases than in
      controls. Eleven (9%) women with PCOS and 21 (17%) controls underwent diagnostic
      or curative surgery (relative risk: 0.56). These results, in contrast to the
      previously published literature, do not allow us to conclude that there is a
      higher risk for BBD among women with PCOS, and the proportion of women with a
      positive family history of breast cancer was significantly greater in women with
      PCOS compared with controls. Our observation is that having PCOS does not appear
      to affect surgeons' decisions to remove BBD.

PMID- 15963208
TI  - Type 2 diabetes mellitus: a cardiovascular perspective.
AB  - Diabetes mellitus is a disease, which is at the epitome of cardiovascular risk
      factors causing considerable morbidity and mortality. In addition to
      microvascular complications, there is two- to six-fold increased risk of
      macrovascular diseases, such as coronary artery disease, peripheral artery
      disease and stroke. While the mortality from coronary artery disease in patients
      without diabetes has declined over the past 20 years, the mortality in men with
      type 2 diabetes mellitus has not changed. Furthermore, the prevalence of diabetes
      in the UK has increased by 30% since 1991 and the same among the world population
      in 2010 is expected to be twice in 1990. This dramatic increase has serious
      implications from a cardiovascular perspective and thus the aggressive management
      of blood pressure, dyslipidaemia and blood glucose in diabetes is of vital
      importance. The aim of this review is to evaluate the current evidence and to
      discuss the implications of type 2 diabetes and its relevance to clinical
      practice in cardiology. We address this broad subject in discussing (i) the
      pathophysiology of cardiovascular disease in the setting of type 2 diabetes and
      (ii) the prevalence of cardiovascular risk, complications and prognostic
      implications in type 2 diabetes, with a discussion of current therapeutic
      interventions for the prevention or delay of these consequences where relevant.

PMID- 15963209
TI  - Cognitive performance in patients with Alzheimer's disease receiving
      cholinesterase inhibitors for up to 5 years.
AB  - The cholinesterase inhibitors (ChE-Is)--rivastigmine, donepezil and galantamine-
      demonstrated efficacy in large, 6-month, double-blind, placebo-controlled trials,
      and are widely used for the symptomatic treatment of patients with mild-to
      moderate Alzheimer's disease (AD). Over the past few years, data have emerged,
      suggesting that these agents may have long-term benefits. These data have been
      summarized in this study, followed by an interpretation of clinical relevance.
      Data were identified by searches of Medline((R)) and references from relevant
      English-language articles. The search words 'Alzheimer', 'donepezil',
      'rivastigmine', 'galantamine' and 'long term' were used. In addition, recent data
      presented at international congresses and/or provided by colleagues in this field
      of research were included in order to ensure maximum topicality. Data are
      available showing cognitive performance in patients remaining on rivastigmine for
      up to 5 years (n = 83), donepezil for up to 4.9 years (n = 18) and galantamine
      for up to 4 years (n = 185). Most of these data come from open-label studies and
      need to be interpreted with caution. The data appear to suggest that patients,
      caregivers and physicians will still see some decline on ChE-Is after a period of
      stabilization, but this may be slower and later than expected if the patients
      were left untreated. This applies across all domains of AD - not simply cognition
      - and function can be relatively preserved, even if cognitive scores are falling.
      Despite the limitations of current data, the information reviewed in this study
      may help practising doctors assess the long-term value of ChE-Is in this
      consistently progressive disease.

PMID- 15963210
TI  - Accelerated atherosclerosis in rheumatoid arthritis and systemic lupus
      erythematosus.
AB  - It is important for primary care physicians to recognise rheumatoid arthritis and
      systemic lupus erythematosus patients as high-risk groups for atherosclerosis,
      requiring aggressive risk-factor modification. Recent studies suggest that this
      increased risk is not explained by an excess of traditional risk factors, but
      rather appears to be related to underlying rheumatic disease activity. Moreover,
      there is emerging data that aggressive treatment with disease-modifying agents
      may reduce the incidence of atherosclerosis in these conditions.

PMID- 15963211
TI  - Overactive bladder: achieving a differential diagnosis from other lower urinary
      tract conditions.
AB  - Overactive bladder (OAB) is a debilitating condition characterised by an urgent
      need to urinate (urgency), often with urinary frequency and, in some cases,
      urgency incontinence and nocturnal frequency. Patients often adopt complex
      adaptive behaviours to cope with their symptoms as OAB can compromise all
      dimensions of a patient's quality of life. Most OAB patients present initially to
      their primary care physician. Diagnosis is based on presenting symptomatology and
      does not require any invasive tests. Direct questioning about symptoms is
      important in achieving a differential diagnosis. The most common condition to be
      considered when working towards a differential diagnosis is a urinary tract
      infection (UTI). However, some physicians have expressed concerns about
      identifying the small number of cases where bladder cancer is a potential
      underlying aetiology for the symptoms of OAB. In this review, we examine the
      prevalence and patient profiles for these bladder conditions and their presenting
      symptomatology. We also review tests that may be recommended to exclude a
      diagnosis of UTI or bladder cancer and present a diagnostic algorithm suitable
      for office-based primary care practice.

PMID- 15963212
TI  - Darifenacin in the treatment of overactive bladder.
AB  - Antimuscarinic drug therapy has been shown to be effective in the management of
      patients with symptoms of the overactive bladder syndrome (OAB), but the
      bothersome antimuscarinic adverse effects of dry mouth, constipation, somnolence
      and blurred vision often affect compliance with medication. The development of
      bladder selective M3 specific antagonists offers the possibility of increasing
      efficacy whilst minimising adverse effects. The M3 specific antagonist
      solifenacin has recently been marketed, and darifenacin will soon be available.
      The purpose of this article is to review the pharmacology and clinical trial data
      available for darifenacin, in addition to examining its role in the treatment of
      the OBS.

PMID- 15963213
TI  - Simultaneous treatment of hypertension and dyslipidaemia may help to reduce
      overall cardiovascular risk: focus on amlodipine/atorvastatin single-pill
      therapy.
AB  - Single-pill amlodipine besylate/atorvastatin calcium (Caduet), Pfizer Inc, NY,
      USA) is the first therapy aimed at the simultaneous treatment of hypertension
      (HTN) and dyslipidaemia (DYS). The benefits of lowering blood pressure (BP) in
      patients with HTN and lowering cholesterol in patients with DYS are well known
      and well studied. However, worldwide, many patients with HTN have concomitant
      DYS, which places them at greater risk for cardiovascular disease compared with
      patients with just one of these risk factors. Clinical trials have demonstrated
      that amlodipine plus atorvastatin can be safely co-administered across the dose
      range. Single-pill amlodipine/atorvastatin reduces both BP and cholesterol and
      may help to improve the management of patients with concomitant HTN and DYS.

PMID- 15963214
TI  - A 5-year audit of haemodialysis access.
AB  - This is a review of our experience with vascular access procedures over a 5-year
      period at Derriford Hospital, Plymouth, UK. The aims of the study were to examine
      the outcome of vascular access procedures and factors influencing access
      survival. Between April 1995 and March 2000, 151 patients who underwent 221
      vascular access procedures were studied. Of these, 136 had autogenous
      arteriovenous fistulae, whereas 85 had prosthetic AV grafts (41% in the thigh).
      The overall primary failure rate was 21% whereas the 1- and 5-year cumulative
      access survival rates were 60 and 41%, respectively. Thigh grafts have a mean
      survival of 36 months compared with 32 months for prosthetic upper limb and 43
      months for autogenous fistulae. Age, diabetes and predialysis status did not
      significantly influence access survival. Thrombosis was responsible for access
      failure in 62 cases (28%). Avoiding subclavian vein canulation and performing
      vessel mapping prior to access placement should reduce the risk of access failure
      due to outflow obstruction.

PMID- 15963215
TI  - Coexistence of Crohn's disease and neuroendocrine tumour of appendix: more than
      coincidence?

PMID- 15963216
TI  - How I do it? Excision of neck lumps under local anaesthesia.
AB  - Excisions of neck lesions under local anaesthesia are made technically more
      difficult by the injection of anaesthetic agent, causing the lesion to become
      less palpable. Pen marking the lesion can circumvent the problem; however, this
      marking often disappears after skin preparation. We describe a technique which
      abolishes this problem.

PMID- 15963217
TI  - Perianal abscesses due to ingested foreign bodies.
AB  - Four cases of perianal abscesses due to foreign bodies (FBs) impacted in the anal
      canal are reported. The clinical presentation mimics common causes of acute anal
      pain. Digital rectal examination under local or general anaesthesia and/or
      proctoscopy can establish the diagnosis, but may miss the presence of an FB.
      Incision and drainage of the abscess along with removal of the FB results in
      immediate pain relief and long-term cure. Impacted FBs must not be overlooked as
      an unusual cause of perianal abscess.

PMID- 15963218
TI  - Volvulus--a rare complication of ileal conduit.
AB  - Conduit volvulus is a very rare complication of ileal conduit. To date, only
      seven surgically confirmed cases have been reported. Conduit volvulus is a
      potentially reversible cause of renal impairment in patients with urinary
      diversion. The diagnosis depends on accurate radiological evaluation. The length
      of the bowel to construct the ileal conduit, closure of defects around the
      conduit and its mesentery and retroperitonealization of ureteroileal anastomosis
      are the determining factors for such a complication.

PMID- 15963219
TI  - Toxic hepatitis associated with paroxetine.
AB  - Hepatotoxicity is a rare complication of paroxetine, a selective serotonin
      reuptake inhibitor. Regarded as safe in therapeutic use, there have been reports
      of cases of severe hepatic dysfunction with gross elevations of transaminase
      levels that may be related to this drug. We report here severe adverse
      cholestatic and hepatocellular injury in a patient taking paroxetine probably due
      to an immune-mediated hypersensitivity reaction.

PMID- 15963220
TI  - Cyclosporine--a treatment and a rare complication: Raynaud's phenomenon.

PMID- 15963221
TI  - Managing chronic headaches in the clinic.

PMID- 15963223
TI  - In response to 'ezetimibe-induced hyperlipidaemia' case report.

PMID- 15963225
TI  - A generic approach for the design of whole-genome oligoarrays, validated for
      genomotyping, deletion mapping and gene expression analysis on Staphylococcus
      aureus.
AB  - BACKGROUND: DNA microarray technology is widely used to determine the expression
      levels of thousands of genes in a single experiment, for a broad range of
      organisms. Optimal design of immobilized nucleic acids has a direct impact on the
      reliability of microarray results. However, despite small genome size and
      complexity, prokaryotic organisms are not frequently studied to validate selected
      bioinformatics approaches. Relying on parameters shown to affect the
      hybridization of nucleic acids, we designed freely available software and
      validated experimentally its performance on the bacterial pathogen Staphylococcus
      aureus. RESULTS: We describe an efficient procedure for selecting 40-60 mer
      oligonucleotide probes combining optimal thermodynamic properties with high
      target specificity, suitable for genomic studies of microbial species. The
      algorithm for filtering probes from extensive oligonucleotides libraries fitting
      standard thermodynamic criteria includes positional information of predicted
      target-probe binding regions. This algorithm efficiently selected probes
      recognizing homologous gene targets across three different sequenced genomes of
      Staphylococcus aureus. BLAST analysis of the final selection of 5,427 probes
      yielded >97%, 93%, and 81% of Staphylococcus aureus genome coverage in strains
      N315, Mu50, and COL, respectively. A manufactured oligoarray including a subset
      of control Escherichia coli probes was validated for applications in the fields
      of comparative genomics and molecular epidemiology, mapping of deletion mutations
      and transcription profiling. CONCLUSION: This generic chip-design process merging
      sequence information from several related genomes improves genome coverage even
      in conserved regions.

PMID- 15963226
TI  - The placental RCAS1 expression during stillbirth.
AB  - BACKGROUND: Independently of the fetal death cause the beginning and course of
      stillbirth is closely related with the growing cytotoxic activity at the maternal
      fetal interface. RCAS1 participates in the inhibition of maternal immune response
      during pregnancy. The alterations of RCAS1 protein expression in placental cells
      seem to determine the beginning of the labor and participate in the placental
      abruption. The aim of the present study was to investigate RCAS1 expression in
      placentas obtained following stillbirths or normal term births. METHODS: RCAS1
      expression was evaluated by Western blot method with the use of monoclonal anti
      RCAS1 antibody in 67 placental tissue samples. Pregnant women were divided into
      four groups according to the mode of labor onset--spontaneous or induced, and the
      type of labor, stillbirth or labor at term. Placental beta-Actin expression was
      chosen as a control protein. Relative amounts of placental RCAS1 were compared
      with the use of Student's t-test, whereas beta-Actin control data were compared
      with the use of Mann-Whitney U test. RESULTS: The average relative amount of
      RCAS1 was significantly lower in women with induced stillbirths than in women
      with induced labor at term. Similarly, significantly lower RCAS1 placental levels
      were observed in patients with spontaneous stillbirths than in women with
      spontaneous labor at term. Significant differences in RCAS1 expression were also
      observed with the respect to the beginning of the stillbirth: spontaneous and
      induced. Lowest RCAS1 placental levels were observed in women with spontaneous
      stillbirth. CONCLUSIONS: These preliminary results indicate that the alterations
      of RCAS1 expression in the human placenta may be involved in the changes of
      maternal immune system that take place during stillbirth.

PMID- 15963227
TI  - Can bile duct injuries be prevented? "A new technique in laparoscopic
      cholecystectomy".
AB  - BACKGROUND: Over the last decade, laparoscopic cholecystectomy has gained
      worldwide acceptance and considered to be as "gold standard" in the surgical
      management of symptomatic cholecystolithiasis. However, the incidence of bile
      duct injury in laparoscopic cholecystectomy is still two times greater compared
      to classic open surgery. The development of bile duct injury may result in
      biliary cirrhosis and increase in mortality rates. The mostly blamed causitive
      factor is the misidentification of the anatomy, especially by a surgeon who is at
      the beginning of his learning curve. Biliary tree injuries may be decreased by
      direct coloration of the cystic duct, ductus choledochus and even the gall
      bladder. METHODS: gall bladder fundus was punctured by Veress needle and all the
      bile was aspirated. The same amount of fifty percent methylene blue diluted by
      saline solution was injected into the gall bladder for coloration of biliary
      tree. The dissection of Calot triangle was much more safely performed after
      obtention of coloration of the gall bladder, cystic duct and choledocus. RESULTS:
      Between October 2003 and December 2004, overall 46 patients (of which 9 males)
      with a mean age of 47 (between 24 and 74) underwent laparoscopic cholecystectomy
      with methylene blue injection technique. The diagnosis of chronic cholecystitis
      (the thickness of the gall bladder wall was normal) confirmed by pre-operative
      abdominal ultrasonography in all patients. The diameters of the stones were
      greater than 1 centimeter in 32 patients and calcula of various sizes being
      smaller than 1 cm. were documented in 13 cases. One patient was operated for gall
      bladder polyp (our first case). Successful coloration of the gall bladder, cystic
      duct and ductus choledochus was possible in 43 patients, whereas only the gall
      bladder and proximal cystic duct were visualised in 3 cases. In these cases,
      ductus choledochus visibility was not possible. None of the patients developed
      bile duct injury. CONCLUSION: The number of bile duct injuries related to
      anatomic misidentification can be decreased and even vanished by using
      intraoperative methylene blue injection technique into the gall bladder fundus
      intraoperatively.

PMID- 15963228
TI  - Insulin resistance in adolescents with Down syndrome: a cross-sectional study.
AB  - BACKGROUND: The prevalence of diabetes mellitus is higher in individuals with
      Down syndrome (DS) than in the general population; it may be due to the high
      prevalence of obesity presented by many of them. The aim of this study was to
      evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model
      Assessment) method, in DS adolescents, describing it according to the sex, body
      mass index (BMI) and pubertal development. METHODS: 15 adolescents with DS (8
      males and 7 females) were studied, aged 10 to 18 years, without history of
      disease or use of medication that could change the suggested laboratory
      evaluation. On physical examination, the pubertal signs, acanthosis nigricans
      (AN), weight and height were evaluated. Fasting plasma glucose and insulin were
      analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was
      calculated using the HOMA method. The patients were grouped into obese,
      overweight and normal, according to their BMI percentiles. The EPIINFO 2004
      software was used to calculate the BMI, its percentile and Z score. RESULTS: Five
      patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II
      IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and
      9 normal. Considering the total number of patients, HOMA was 1.7 +/- 1.0, insulin
      9.3 +/- 4.8 microU/ml and glucose 74.4 +/- 14.8 mg/dl. The HOMA values were 2.0
      +/- 1.0 in females and 1.5 +/- 1.0 in males. Considering the nutritional
      classification, the values of HOMA and insulin were: HOMA: 3.3 +/- 0.6, 2.0 +/-
      1.1 and 1.3 +/- 0.6, and insulin: 18.15 +/- 1.6 microU/ml, 10.3 +/- 3.5 microU/ml
      and 6.8 +/- 2.8 microU/ml, in the obese, overweight and normal groups
      respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5
      +/- 1.3, 1.4 +/- 0.6 and 0.8 +/- 0.0, and insulin: 13.0 +/- 5.8 microU/ml, 7.8 +/
      2.9 microU/ml and 4.0 +/- 0.0 microU/ml, in the adult, pubertal and prepubertal
      groups respectively. CONCLUSION: The obese and overweight, female and adult
      patients showed the highest values of HOMA and insulin.

PMID- 15963229
TI  - Down syndrome, paternal age and education: comparison of California and the Czech
      Republic.
AB  - BACKGROUND: The association between maternal age and risk of Down syndrome has
      been repeatedly shown in various populations. However, the effect of paternal age
      and education of parents has not been frequently studied. Comparative studies on
      Down syndrome are also rare. This study evaluates the epidemiological
      characteristics of Down syndrome in two culturally and socially contrasting
      population settings, in California and the Czech Republic. METHODS: The observed
      live birth prevalence of Down syndrome was studied among all newborns in the
      California counties monitored by California Birth Defects Monitoring Program from
      1996 to 1997, and in the whole Czech Republic from 1994 to 1998. Logistic
      regression was used to analyze the data. RESULTS: A total of 516,745 (California)
      and 475,834 (the Czech Republic) infants were included in the analysis. Among
      them, 593 and 251, respectively, had Down syndrome. The mean maternal age of
      children with Down syndrome was 32.1 years in California and 26.9 years in the
      Czech Republic. Children born to older mothers were at greater risk of Down
      syndrome in both populations. The association with paternal age was mostly
      explained by adjusting for maternal age, but remained significant in the Czech
      Republic. The association between maternal education and Down syndrome was much
      stronger in California than in the Czech Republic but parental age influences
      higher occurrence of Down syndrome both in California and in the Czech Republic.
      CONCLUSION: The educational gradient in California might reflect selective impact
      of prenatal diagnosis, elective termination, and acceptance of prenatal
      diagnostic measures in Californian population.

PMID- 15963230
TI  - pSLIP: SVM based protein subcellular localization prediction using multiple
      physicochemical properties.
AB  - BACKGROUND: Protein subcellular localization is an important determinant of
      protein function and hence, reliable methods for prediction of localization are
      needed. A number of prediction algorithms have been developed based on amino acid
      compositions or on the N-terminal characteristics (signal peptides) of proteins.
      However, such approaches lead to a loss of contextual information. Moreover,
      where information about the physicochemical properties of amino acids has been
      used, the methods employed to exploit that information are less than optimal and
      could use the information more effectively. RESULTS: In this paper, we propose a
      new algorithm called pSLIP which uses Support Vector Machines (SVMs) in
      conjunction with multiple physicochemical properties of amino acids to predict
      protein subcellular localization in eukaryotes across six different locations,
      namely, chloroplast, cytoplasmic, extracellular, mitochondrial, nuclear and
      plasma membrane. The algorithm was applied to the dataset provided by Park and
      Kanehisa and we obtained prediction accuracies for the different classes ranging
      from 87.7%-97.0% with an overall accuracy of 93.1%. CONCLUSION: This study
      presents a physicochemical property based protein localization prediction
      algorithm. Unlike other algorithms, contextual information is preserved by
      dividing the protein sequences into clusters. The prediction accuracy shows an
      improvement over other algorithms based on various types of amino acid
      composition (single, pair and gapped pair). We have also implemented a web server
      to predict protein localization across the six classes (available at
      http://pslip.bii.a-star.edu.sg/).

PMID- 15963231
TI  - Cognate peptide-receptor ligand mapping by directed phage display.
AB  - BACKGROUND: A rapid phage display method for the elucidation of cognate peptide
      specific ligand for receptors is described. The approach may be readily
      integrated into the interface of genomic and proteomic studies to identify
      biologically relevant ligands. METHODS: A gene fragment library from influenza
      coat protein haemagglutinin (HA) gene was constructed by treating HA cDNA with
      DNAse I to create 50-100 bp fragments. These fragments were cloned into plasmid
      pORFES IV and in-frame inserts were selected. These in-frame fragment inserts
      were subsequently cloned into a filamentous phage display vector JC-M13-88 for
      surface display as fusions to a synthetic copy of gene VIII. Two well
      characterized antibodies, mAb 12CA5 and pAb 07431, directed against distinct
      known regions of HA were used to pan the library. RESULTS: Two linear epitopes,
      HA peptide 112-126 and 162-173, recognized by mAb 12CA5 and pAb 07431,
      respectively, were identified as the cognate epitopes. CONCLUSION: This approach
      is a useful alternative to conventional methods such as screening of overlapping
      synthetic peptide libraries or gene fragment expression libraries when searching
      for precise peptide protein interactions, and may be applied to functional
      proteomics.

PMID- 15963232
TI  - A description of physical therapists' knowledge in managing musculoskeletal
      conditions.
AB  - BACKGROUND: Physical therapists increasingly provide direct access services to
      patients with musculoskeletal conditions, and growing evidence supports the cost
      effectiveness of this mode of healthcare delivery. However, further evidence is
      needed to determine if physical therapists have the requisite knowledge necessary
      to manage musculoskeletal conditions. Therefore, the purpose of this study was to
      describe physical therapists' knowledge in managing musculoskeletal conditions.
      METHODS: This study utilized a cross-sectional design in which 174 physical
      therapist students from randomly selected educational programs and 182
      experienced physical therapists completed a standardized examination assessing
      knowledge in managing musculoskeletal conditions. This same examination has been
      previously been used to assess knowledge in musculoskeletal medicine among
      medical students, physician interns and residents, and across a variety of
      physician specialties. RESULTS: Experienced physical therapists had higher levels
      of knowledge in managing musculoskeletal conditions than medical students,
      physician interns and residents, and all physician specialists except for
      orthopaedists. Physical therapist students enrolled in doctoral degree
      educational programs achieved significantly higher scores than their peers
      enrolled in master's degree programs. Furthermore, experienced physical
      therapists who were board-certified in orthopaedic or sports physical therapy
      achieved significantly higher scores and passing rates than their non board
      certified colleagues. CONCLUSION: The results of this study may have implications
      for health and public policy decisions regarding the suitability of utilizing
      physical therapists to provide direct access care for patients with
      musculoskeletal conditions.

PMID- 15963233
TI  - Carvacrol and p-cymene inactivate Escherichia coli O157:H7 in apple juice.
AB  - BACKGROUND: Outbreaks of food poisoning associated with drinking un-pasteurised
      apple juice contaminated with enterohaemorrhagic Escherichia coli O157:H7 are a
      cause of serious illness and occasionally death. Whilst a well-established heat
      process (pasteurisation) will readily eliminate the pathogen, some consumers are
      demanding more fresh-like foods that have not been subjected to processing
      methods that are perceived as severe and may lead to loss of flavour and
      vitamins. Therefore, alternative methods are being investigated to replace
      pasteurisation and improve the safety of minimally-processed juices. The addition
      of natural antimicrobial substances such as the phenolic substances carvacrol and
      p-cymene (derived from the essential oils of herbs and spices) provides a
      potential new route to assure safety and extend the shelf-life of raw fruit
      juices. The aim of this study was to evaluate the addition of very low
      concentrations (0.25-1.25 mM) of carvacrol and p-cymene both individually and in
      combination as a novel means of controlling Escherichia coli O157:H7 in un
      pasteurised apple juice. RESULTS: When inoculated at a level of 4 log CFU/ml into
      un-pasteurised apple juice (pH 3.20 +/- 0.06), Escherichia coli O157:H7 survived
      for up to 3 and 19 days at 25 degrees and 4 degrees C, respectively. Treatment of
      the juice with 1.25 mM carvacrol or p-cymene reduced the numbers of E. coli
      O157:H7 to undetectable levels within 1-2 days at both storage temperatures. The
      effective concentrations of carvacrol could be reduced even further by combining
      it at 0.5 mM with cymene at 0.25 mM. The phenolic compounds were biocidal against
      both spoilage yeasts and E. coli O157:H7 thereby increasing the shelf-life and
      improving the safety of un-pasteurised apple juice, particularly when stored at
      chill temperatures. CONCLUSION: The results showed that the natural antimicrobial
      compounds carvacrol and p-cymene could potentially be used to extend the shelf
      life and improve the safety margins in un-pasteurised chilled fruit juices.

PMID- 15963235
TI  - Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a
      male: case report and review of the literature.
AB  - SUMMARY:  BACKGROUND: Secretory carcinoma (SC) of the breast is a rare and
      indolent tumor. Although originally described in children, it is now known to
      occur in adults of both sexes. Recently, the tumor was associated with the ETV6
      NTRK3 gene translocation. CASE PRESENTATION: A 52-year-old male was diagnosed
      with secretory breast carcinoma and underwent a modified radical mastectomy. At
      18 months the tumor recurred at the chest wall and the patient developed lung
      metastases. He was treated concurrently with radiation and chemotherapy without
      response. His tumor showed the ETV6-NTRK3 translocation as demonstrated by
      fluorescent in situ hybridization (FISH). CONCLUSION: SC is a rare slow-growing
      tumor best treated surgically. There are insufficient data to support the use of
      adjuvant radiation or chemotherapy. Its association with the ETV6-NTRK3 fusion
      gene gives some clues for the better understanding of this neoplasm and
      eventually, the development of specific therapies.

PMID- 15963234
TI  - Zinc-finger domains of the transcriptional repressor KLF15 bind multiple sites in
      rhodopsin and IRBP promoters including the CRS-1 and G-rich repressor elements.
AB  - BACKGROUND: In the retina, many of the genes that encode components of the visual
      transduction cascade and retinoid recycling are exclusively expressed in
      photoreceptor cells and show highly stereotyped temporal and spatial expression
      patterns. Multiple transcriptional activators of photoreceptor-specific genes
      have been identified, but little is known about negative regulation of gene
      expression in the retina. We recently identified KLF15, a member of the
      Sp/Kruppel-like Factor family of zinc-finger containing transcription factors, as
      an in vitro repressor of the promoters of the photoreceptor-specific genes
      rhodopsin and IRBP/Rbp3. To gain further insight into the mechanism of KLF15
      mediated regulation of gene expression, we have characterized the binding
      characteristics and specificity of KLF15's DNA binding domains and defined the
      KLF15 binding sites in the rhodopsin and IRBP promoters. RESULTS: In EMSA and
      DNAseI footprinting assays, a KLF15-GST fusion protein containing the C-terminal
      zinc-finger domains (123 amino acids) showed zinc-dependent and sequence-specific
      binding to a 9 bp consensus sequence containing a core CG/TCCCC. Both the bovine
      rhodopsin and IRBP promoters contained multiple KLF15 binding sites that included
      the previously identified CRS-1 and G-rich repressor elements. KLF15 binding
      sites were highly conserved between the bovine, human, chimp and dog rhodopsin
      promoters, but less conserved in rodents. KLF15 reduced luciferase expression by
      bRho130-luc (containing 4 KLF15 sites) and repressed promoter activation by CRX
      (cone rod homeobox) and/or NRL (neural retina leucine zipper), although the
      magnitude of the reduction was smaller than previously reported for a longer
      bRho225-luc (containing 6 KFL15 sites). CONCLUSION: KLF15 binds to multiple 9 bp
      consensus sites in the Rhodospin and IRBP promoters including the CRS-1 and G
      rich repressor elements. Based on the known expression pattern of KLF15 in non
      photoreceptor cells, we hypothesize an in vivo role for KLF15 in repressing
      photoreceptor-specific gene expression in the inner retina.

PMID- 15963237
TI  - A 63 element 1.75 dimensional ultrasound phased array for the treatment of benign
      prostatic hyperplasia.
AB  - BACKGROUND: Prostate cancer and benign prostatic hyperplasia are very common
      diseases in older American men, thus having a reliable treatment modality for
      both diseases is of great importance. The currently used treating options, mainly
      surgical ones, have numerous complications, which include the many side effects
      that accompany such procedures, besides the invasive nature of such techniques.
      Focused ultrasound is a relatively new treating modality that is showing
      promising results in treating prostate cancer and benign prostatic hyperplasia.
      Thus this technique is gaining more attention in the past decade as a non
      invasive method to treat both diseases. METHODS: In this paper, the design,
      construction and evaluation of a 1.75 dimensional ultrasound phased array to be
      used for treating prostate cancer and benign prostatic hyperplasia is presented.
      With this array, the position of the focus can be controlled by changing the
      electrical power and phase to the individual elements for electronically focusing
      and steering in a three dimensional volume. The array was designed with a maximum
      steering angle of +/- 13.5 degrees in the transverse direction and a maximum
      depth of penetration of 11 cm, which allows the treatment of large prostates. The
      transducer piezoelectric ceramic, matching layers and cable impedance have been
      designed for maximum power transfer to tissue. RESULTS: To verify the capability
      of the transducer for focusing and steering, exposimetry was performed and the
      results correlated well with the calculated field. Ex vivo experiments using
      bovine tissue were performed with various lesion sizes and indicated the
      capability of the transducer to ablate tissue using short sonications.
      CONCLUSION: A 1.75 dimensional array, that overcame the drawbacks associated with
      one-dimensional arrays, has been designed, built and successfully tested. Design
      issues, such as cable and ceramic capacitances, were taken into account when
      designing this array. The final prototype overcame also the problem of generating
      grating lobes at unwanted locations by tapering the array elements.

PMID- 15963238
TI  - Evidence-based patient choice: a prostate cancer decision aid in plain language.
AB  - BACKGROUND: Decision aids (DA) to assist patients in evaluating treatment options
      and sharing in decision making have proliferated in recent years. Most require
      high literacy and do not use plain language principles. We describe one of the
      first attempts to design a decision aid using principles from reading research
      and document design. The plain language DA prototype addressed treatment
      decisions for localized prostate cancer. Evaluation assessed impact on knowledge,
      decisions, and discussions with doctors in men newly diagnosed with prostate
      cancer. METHODS: Document development steps included preparing an evidence-based
      DA in standard medical parlance, iteratively translating it to emphasize shared
      decision making and plain language in three formats (booklet, Internet, and audio
      tape). Scientific review of medical content was integrated with expert health
      literacy review of document structure and design. Formative evaluation methods
      included focus groups (n = 4) and survey of a new sample of men newly diagnosed
      with prostate cancer (n = 60), compared with historical controls (n = 184).
      RESULTS: A transparent description of the development process and design elements
      is reported. Formative evaluation among newly diagnosed prostate cancer patients
      found the DA to be clear and useful in reaching a decision. Newly diagnosed
      patients reported more discussions with doctors about treatment options, and
      showed increases in knowledge of side effects of radiation therapy. CONCLUSION:
      The plain language DA presenting medical evidence in text and numerical formats
      appears acceptable and useful in decision-making about localized prostate cancer
      treatment. Further testing should evaluate the impact of all three media on
      decisions made and quality of life in the survivorship period, especially among
      very low literacy men.

PMID- 15963236
TI  - Echocardiography-based left ventricular mass estimation. How should we define
      hypertrophy?
AB  - Left ventricular hypertrophy is an important risk factor in cardiovascular
      disease and echocardiography has been widely used for diagnosis. Although an
      adequate methodologic standardization exists currently, differences in
      measurement and interpreting data is present in most of the older clinical
      studies. Variability in border limits criteria, left ventricular mass formulas,
      body size indexing and other adjustments affects the comparability among these
      studies and may influence both the clinical and epidemiologic use of
      echocardiography in the investigation of the left ventricular structure. We are
      going to review the most common measures that have been employed in left
      ventricular hypertrophy evaluation in the light of some recent population based
      echocardiographic studies, intending to show that echocardiography will remain a
      relatively inexpensive and accurate tool diagnostic tool.

PMID- 15963239
TI  - Insufficient neutralization in testing a chlorhexidine-containing ethanol-based
      hand rub can result in a false positive efficacy assessment.
AB  - BACKGROUND: Effective neutralization in testing hand hygiene preparations is
      considered to be a crucial element to ensure validity of the test results,
      especially with the difficulty to neutralize chlorhexidine gluconate. Aim of the
      study was to measure the effect of chemical neutralization under practical test
      conditions according to EN 1500. METHODS: We have investigated two ethanol-based
      hand rubs (product A, based on 61% ethanol and 1% chlorhexidine gluconate;
      product B, based on 85% ethanol). The efficacy of products (application of 3 ml
      for 30 s) was compared to 2-propanol 60% (v/v) (two 3 ml rubs of 30 s each) on
      hands artificially contaminated with Escherichia coli using a cross-over design
      with 15 volunteers. Pre-values were obtained by rubbing fingertips for 1 minute
      in liquid broth. Post-values were determined by sampling immediately after
      disinfection in liquid broth with and without neutralizers (0.5% lecithin, 4%
      polysorbate 20). RESULTS: The neutralizers were found to be effective and non
      toxic. Without neutralization in the sampling fluid, the reference disinfection
      reduced the test bacteria by 3.7 log10, product B by 3.3 log10 and product A by
      4.8 log10 (P = 0.001; ANOVA). With neutralization the reference disinfection
      reduced the test bacteria by 3.5 log10, product B by 3.3 log10 and product A by
      2.7 log10 (P = 0.011; ANOVA). In comparison to the reference treatment Product B
      lead to a lower mean reduction than the reference disinfection but the difference
      was not significant (P > 0.1; Wilcoxon-Wilcox test). Without neutralizing agents
      in the sampling fluid, product A yielded a significantly higher reduction of test
      bacteria (4.8; P = 0.02) as compared to the situation with neutralizing agents
      (2.7; P = 0.033). CONCLUSION: The crucial step of neutralization lies in the
      sampling fluid itself in order to stop any residual bacteriostatic or
      bactericidal activity immediately after the application of the preparation,
      especially with chlorhexidine gluconate-containing preparations. This is
      particularly important at short application times such as the 30 s.

PMID- 15963240
TI  - Genetic lesions within the 3a gene of SARS-CoV.
AB  - A series of frameshift mutations within the 3a gene has been observed in culture
      derived severe acute respiratory syndrome coronavirus (SARS-CoV). We report here
      that viral RNA from clinical samples obtained from SARS-CoV infected patients
      also contains a heterogeneous population of wild-type and mutant 3a transcripts.

PMID- 15963241
TI  - Anti-proliferative effects, cell cycle G2/M phase arrest and blocking of
      chromosome segregation by probimane and MST-16 in human tumor cell lines.
AB  - BACKGROUND: Anticancer bisdioxopiperazines, including ICRF-154, razoxane (Raz,
      ICRF-159) and ICRF-193, are a family of anticancer agents developed in the UK,
      especially targeting metastases of neoplasms. Two other bisdioxopiperazine
      derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai
      Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
      Cytotoxic activities and mechanisms of Raz (+)-steroisomer (ICRF-187,
      dexrazoxane), Pro and MST-16 against tumor cells were evaluated by MTT
      colorimetry, flow cytometry and karyotyping. RESULTS: Pro was cytotoxic to human
      tumor cell lines in vitro (IC50<50 microM for 48 h). Four human tumor cell lines
      (SCG-7901, K562, A549 and HL60) were susceptible to Pro at low inhibitory
      concentrations (IC50 values < 10 microM for 48 h). Although the IC50 against HeLa
      cell line of vincristine (VCR, 4.56 microM), doxorubicin (Dox, 1.12 microM) and 5
      fluoruouracil (5-Fu, 0.232 microM) are lower than Pro (5.12 microM), ICRF-187
      (129 microM) and MST-16 (26.4 microM), VCR, Dox and 5-Fu shows a low dose-related
      - high cytotoxic activity. Time-response studies showed that the cytotoxic
      effects of Pro are increased for 3 days in human tumor cells, whereas VCR, Dox
      and 5-Fu showed decreased cytotoxic action after 24 h. Cell cycle G2/M phase
      arrest and chromosome segregation blocking by Pro and MST-16 were noted. Although
      there was similar effects of Pro and MST-16 on chromosome segregation blocking
      action and cell cycle G2/M phase arrest at 1- 4 microM, cytotoxicity of Pro
      against tumor cells was higher than that of MST-16 in vitro by a factor of 3- 10
      folds. Our data show that Pro may be more effective against lung cancer and
      leukemia while ICRF-187 and MST-16 shows similar IC50 values only against
      leukemia. CONCLUSION: It suggests that Pro has a wider spectrum of cytotoxic
      effects against human tumor cells than other bisdioxopiperazines, especially
      against solid tumors, and with a single cytotoxic pathway of Pro and MST-16
      affecting chromosome segregation and leading also to cell G2/ M phase arrests,
      which finally reduces cell division rates. Pro may be more potent than MST-16 in
      cytotoxicity. High dose- and time- responses of Pro, when compared with VCR, 5-Fu
      and Dox, were seen that suggest a selectivity of Pro against tumor growth.
      Compounds of bisdioxopiperazines family may keep up their cytotoxic effects
      longer than many other anticancer drugs.

PMID- 15963242
TI  - The effects of zotepine in treating psychotic patients with hyperuricaemia: a
      case series.

PMID- 15963243
TI  - Amitriptyline and nortriptyline inhibit interleukin-1 release by rat mixed glial
      and microglial cell cultures.
AB  - Pro-inflammatory cytokines, such as interleukin (IL)-1beta and tumour necrosis
      factor (TNF)-alpha have been suggested to be involved in the pathophysiology of
      depression and in the mechanism of action of antidepressant drugs. Until now the
      effect of antidepressants on cytokines has been examined only in plasma, blood
      mononuclear cells and spleen, which reflect the activity of peripheral cytokine
      network. The aim of this study was to evaluate the effect of amitriptyline and
      its metabolite nortriptyline on the release of IL-1beta and TNF-alpha by
      lipopolysaccharide (LPS)-activated rat mixed glial and microglial cell cultures.
      LPS stimulated the release of both cytokines. The exposure of mixed glial culture
      to amitriptyline and nortriptyline led to a decrease in both IL-1beta and TNF
      alpha release. Moreover, amitriptyline reduced LPS-stimulated IL-1beta release by
      microglial cultures. Although amitriptyline reduced secretion of both cytokines,
      the drug did not affect IL-1beta and TNF-alpha mRNAs in mixed cell cultures. Our
      study has shown for the first time that amitriptyline and nortriptyline
      administered at concentrations which may be achieved in plasma and brain
      structures during treatment, inhibit the secretion of IL-1beta and TNF-alpha in
      rat mixed glial and microglial cell cultures. The obtained results support the
      previous observations that antidepressants are able to reduce peripheral release
      of pro-inflammatory cytokines and suggest that the cytokine network may be
      involved in the central mechanism of action of amitriptyline and nortriptyline.

PMID- 15963244
TI  - QTc interval prolongation and antipsychotic drug treatments: focus on sertindole.
AB  - Since the 1960s, physicians have been aware of electrocardiographic (ECG)
      abnormalities and cases of sudden death associated with the use of antipsychotic
      drugs in patients with schizophrenia. Explanations for such deaths have
      traditionally focused on drug-induced prolongation of the QT interval leading to
      the development of life-threatening ventricular arrhythmias such as torsade de
      pointes (TdP). It is now apparent that most conventional and atypical
      antipsychotics can cause dose-related prolongation of the corrected QT interval
      (QTc), although there are important differences in the potency of individual
      agents. This review discusses potential mechanisms underlying QTc prolongation
      and arrhythmogenesis and examines the evidence for a relationship between
      antipsychotic drugs and prolongation of the QTc interval. New
      electrophysiological and epidemiological data are presented which suggest there
      may not be a clear-cut cause-effect relationship between QTc prolongation and the
      development of ventricular tachyarrhythmias for all atypical antipsychotics. For
      at least one of these agents (sertindole), counterbalancing mechanisms may act to
      reduce the risk of proarrhythmic activity arising as a result of QTc
      prolongation.

PMID- 15963245
TI  - Frontiers in research into interstitial cells of Cajal.

PMID- 15963246
TI  - Interstitial cells in the vasculature.
AB  - Interstitial cells of Cajal are believed to play an important role in
      gastrointestinal tissues by generating and propagating electrical slow waves to
      gastrointestinal muscles and/or mediating signals from the enteric nervous
      system. Recently cells with similar morphological characteristics have been found
      in the wall of blood vessels such as rabbit portal vein and guinea pig mesenteric
      artery. These non-contractile cells are characterised by the presence of numerous
      processes and were easily detected in the wall of the rabbit portal vein by
      staining with methylene blue or by antibodies to the marker of Interstitial Cells
      of Cajal c-kit. These vascular cells have been termed "interstitial cells" by
      analogy with interstitial cells found in the gastrointestinal tract. Freshly
      dispersed interstitial cells from rabbit portal vein and guinea pig mesenteric
      artery displayed various Ca2+-release events from endo/sarcoplasmic reticulum
      including fast localised Ca2+ transients (Ca2+ sparks) and longer and slower Ca2+
      events. Single interstitial cells from the rabbit portal vein, which is a
      spontaneously active vessel, also demonstrated rhythmical Ca2+ oscillations
      associated with membrane depolarisations, which suggests that in this vessel
      interstitial cells may act as pacemakers for smooth muscle cells. The function of
      interstitial cells from the mesenteric arteries is yet unknown. This article
      reviews some of the recent findings regarding interstitial cells from blood
      vessels obtained by our laboratory using electron microscopy,
      immunohistochemistry, tight-seal patch-clamp recording, and fluorescence confocal
      imaging techniques.

PMID- 15963247
TI  - IFN-zeta/ limitin: a member of type I IFN with mild lympho-myelosuppression.
AB  - Interferon (IFN)-Zeta/limitin has been considered as a novel type I IFN by the
      Nomenclature Committee of the International Society for Interferon and Cytokine
      Research. IFN-Zeta/limitin shows some sequence homology with IFN-alpha and IFN
      beta, has a globular structure with five alpha-helices and four loops, and
      recognizes IFN-alpha/beta receptor. Although IFN-zeta/limitin displays antiviral,
      immunomodulatory, and antitumor effects, it has much less lympho-myelosuppressive
      activities than IFN-alpha. Treatment of cells with type I IFNs induces and/or
      activates a number of molecules, which regulate cell cycle and apoptosis. It is
      noteworthy that IFN-zeta/limitin activates the Tyk2-Daxx and Tyk2-Crk pathways
      weaker than IFN-alpha. Because experiments using antisense oligonucleotides have
      revealed their essential role in type I IFN-related suppression of lympho
      hematopoiesis, little ability of IFN-zeta/limitin to activate the Tyk2-dependent
      signaling pathway may explain its uniquely narrow range of biological activities.
      Further analysis of structure-function relationship of type I IFNs will establish
      an engineered cytokine with useful features of IFN-zeta/limitin.

PMID- 15963248
TI  - L-selectin: mechanisms and physiological significance of ectodomain cleavage.
AB  - L-selectin is a cell adhesion molecule consisting of a large, highly
      glycosylated, extracellular domain, a single spanning transmembrane domain and a
      small cytoplasmic tail. It is expressed on most leukocytes and is involved in
      their rolling on inflamed vascular endothelium prior to firm adhesion and
      transmigration. It is also required for the constitutive trafficking of
      lymphocytes through secondary lymphoid organs. Like most adhesion molecules, L
      selectin function is regulated by a variety of mechanisms including gene
      transcription, post-translational modifications, association with the actin
      cytoskeleton, and topographic distribution. In addition, it is rapidly
      downregulated by proteolytic cleavage near the cell surface by ADAM-17 (TACE) and
      at least one other "sheddase". This process of "ectodomain shedding" results in
      the release of most of the extracellular portion of L-selectin from the cell
      surface while retaining the cytoplasmic, transmembrane, and eleven amino acids of
      the extracellular domain on the cell. This review will examine the mechanism(s)
      of L-selectin ectodomain shedding and discuss the physiological implications.

PMID- 15963249
TI  - Matrix metalloproteinases and angiogenesis.
AB  - Matrix metalloproteinases (MMPs) are a family of enzymes that proteolytically
      degrade various components of the extracellular matrix (ECM). Angiogenesis is the
      process of forming new blood vessels from existing ones and requires degradation
      of the vascular basement membrane and remodeling of the ECM in order to allow
      endothelial cells to migrate and invade into the surrounding tissue. MMPs
      participate in this remodeling of basement membranes and ECM. However, it has
      become clear that MMPs contribute more to angiogenesis than just degrading ECM
      components. Specific MMPs have been shown to enhance angiogenesis by helping to
      detach pericytes from vessels undergoing angiogenesis, by releasing ECM-bound
      angiogenic growth factors, by exposing cryptic proangiogenic integrin binding
      sites in the ECM, by generating promigratory ECM component fragments, and by
      cleaving endothelial cell-cell adhesions. MMPs can also contribute negatively to
      angiogenesis through the generation of endogenous angiogenesis inhibitors by
      proteolytic cleavage of certain collagen chains and plasminogen and by modulating
      cell receptor signaling by cleaving off their ligand-binding domains. A number of
      inhibitors of MMPs that show antiangiogenic activity are already in early stages
      of clinical trials, primarily to treat cancer and cancer-associated angiogenesis.
      However, because of the multiple effects of MMPs on angiogenesis, careful testing
      of these MMP inhibitors is necessary to show that these compounds do not actually
      enhance angiogenesis.

PMID- 15963250
TI  - Angiogenesis inhibitors found within the haemostasis pathway.
AB  - Angiogenesis, the development of new blood vessels from the existing vasculature,
      and haemostasis, the coagulation cascade leading to formation of a clot, are
      among the most consistent host responses associated with cancer. Importantly,
      these two pathways interrelate, with blood coagulation and fibrinolysis
      influencing tumor angiogenesis directly, thereby contributing to tumor growth.
      Moreover, many endogenous inhibitors of angiogenesis are found within platelets
      or harboured as cryptic fragments of haemostatic proteins. In this review we
      outline ways in which angiogenesis is coordinated and regulated by haemostasis in
      human cancer. Then we detail the experimental and pre-clinical evidence for the
      ability of many of these endogenous proteins to inhibit tumor angiogenesis and
      thus their potential to be anti-cancer agents, with particular reference to any
      clinical trials.

PMID- 15963251
TI  - Neural stem cells in inflammatory CNS diseases: mechanisms and therapy.
AB  - Autoimmune inflammatory diseases of the central nervous system (CNS) are highly
      complex in their interaction of different cell populations. The main therapy
      focus in the last years has been the inhibition of the immune system. Recent
      progress has shown that endogenous as well as transplanted neural stem cells
      might positively influence the outcome of such diseases. In this review, we
      discuss the current concept of the underlying pathogenesis with a specific focus
      on local CNS cells and potential treatment options.

PMID- 15963252
TI  - Reprogramming mediated by stem cell fusion.
AB  - Advances in mammalian cloning prove that somatic nuclei can be reprogrammed to a
      state of totipotency by transfer into oocytes. An alternative approach to
      reprogram the somatic genome involves the creation of hybrids between somatic
      cells and other cells that contain reprogramming activities. Potential fusion
      partners with reprogramming activities include embryonic stem cells, embryonic
      germ cells, embryonal carcinoma cells, and even differentiated cells. Recent
      advances in fusion-mediated reprogramming are discussed from the standpoints of
      the developmental potency of hybrid cells, genetic and epigenetic correlates of
      reprogramming, and other aspects involved in the reprogramming process. In
      addition, the utility of fusion-mediated reprogramming for future cell-based
      therapies is discussed.

PMID- 15963253
TI  - Identification and expansion of pancreatic stem/progenitor cells.
AB  - Pancreatic islet transplantation represents an attractive approach for the
      treatment of diabetes. However, the limited availability of donor islets has
      largely hampered this approach. In this respect, the use of alternative sources
      of islets such as the ex vivo expansion and differentiation of functional
      endocrine cells for treating diabetes has become the major focus of diabetes
      research. Adult pancreatic stem cells /progenitor cells have yet to be recognized
      because limited markers exist for their identification. While the pancreas has
      the capacity to regenerate under certain circumstances, questions where adult
      pancreatic stem/progenitor cells are localized, how they are regulated, and even
      if the pancreas harbors a stem cell population need to be resolved. In this
      article, we review the recent achievements both in the identification as well as
      in the expansion of pancreatic stem/progenitor cells.

PMID- 15963254
TI  - Pathways of apoptosis and importance in development.
AB  - The elimination of cells by programmed cell death is a fundamental event in
      development where multicellular organisms regulate cell numbers or eliminate
      cells that are functionally redundant or potentially detrimental to the organism.
      The evolutionary conservation of the biochemical and genetic regulation of
      programmed cell death across species has allowed the genetic pathways of
      programmed cell death determined in lower species, such as the nematode
      Caenorhabditis elegans and the fruitfly Drosophila melanogaster to act as models
      to delineate the genetics and regulation of cell death in mammalian cells. These
      studies have identified cell autonomous and non-autonomous mechanisms that
      regulate of cell death and reveal that developmental cell death can either be a
      pre-determined cell fate or the consequence of insufficient cell interactions
      that normally promote cell survival.

PMID- 15963256
TI  - Permeability properties of a three-cell type in vitro model of blood-brain
      barrier.
AB  - We previously found that RBE4.B brain capillary endothelial cells (BCECs) form a
      layer with blood-brain barrier (BBB) properties if co-cultured with neurons for
      at least one week. As astrocytes are known to modulate BBB functions, we further
      set a culture system that included RBE4.B BCECs, neurons and astrocytes. In order
      to test formation of BBB, we measured the amount of 3H-sucrose able to cross the
      BCEC layer in this three-cell type model of BBB. Herein we report that both
      neurons and astrocytes induce a decrease in the permeability of the BCEC layer to
      sucrose. These effects are synergic as if BCECs are cultured with both neurons
      and astrocytes for 5 days, permeability to sucrose decreases even more. By
      Western analysis, we also found that, in addition to the canonical 60 kDa
      occludin, anti-occludin antibodies recognize a smaller protein of 48 kDa which
      accumulates during rat brain development. Interestingly this latter protein is
      present at higher amounts in endothelial cells cultured in the presence of both
      astrocytes and neurons, that is in those conditions in which sucrose permeation
      studies indicate formation of BBB.

PMID- 15963255
TI  - Survivin as a target for new anticancer interventions.
AB  - Survivin is a member of the inhibitor of apoptosis protein (IAP) family, that has
      been implicated in both control of cell division and inhibition of apoptosis.
      Specifically, its anti-apoptotic function seems to be related to the ability to
      directly or indirectly inhibit caspases. Survivin is selectively expressed in the
      most common human neoplasms and appears to be involved in tumor cell resistance
      to some anticancer agents and ionizing radiation. On the basis of these findings
      survivin has been proposed as an attractive target for new anticancer
      interventions. Several preclinical studies have demonstrated that down-regulation
      of survivin expression/function, accomplished through the use of antisense
      oligonucleotides, dominant negative mutants, ribozymes, small interfering RNAs
      and cyclin-dependent kinase inhibitors, increased the apoptotic rate, reduced
      tumor-growth potential and sensitized tumor cells to chemotherapeutic drugs with
      different action mechanisms and gamma-irradiation in in vitro and in vivo models
      of different human tumor types.

PMID- 15963257
TI  - Direct interaction between SNAP-23 and L-type Ca2+ channel.
AB  - During secretion, membrane-bound secretory vesicles dock and fuse at the base of
      porosomes in the cell plasma membrane. Among other proteins, the porosome is
      composed of SNAREs and Ca2+-channels. Ca2+-channels and SNAREs have been
      implicated in cell secretion. Several immunoprecipitation and binding studies
      suggest the physical interaction of the t-SNARE proteins, Syntaxin-1 and SNAP-25
      with various Ca2+-channels. In this study, using yeast two-hybrid and
      immunoanalysis, we demonstrate for the first time, direct interaction of SNAP-23
      and a L-type Ca2+-channel at the plasma membrane in pancreas.

PMID- 15963258
TI  - Activation of focal adhesion kinase in human lung cancer cells involves multiple
      and potentially parallel signaling events.
AB  - Integrins are adhesion receptors that transmit signals bidirectionally across the
      plasma membrane. In our previous report we have shown that the squamous lung
      cancer cell line, Calu-1, binds to collagen type IV (Coll IV) through beta1
      integrin and results in phosphorylation of focal adhesion kinase (FAK) (Ann
      Thorac Surg 2004; 78:450-457). Considering the critical role of FAK in cell
      migration, proliferation, and survival, here we investigated potential mechanisms
      of its activation and regulation in Calu-1 cells. We observed the phosphorylation
      of Tyr397 of FAK (the autophosphorylation site of FAK) and paxillin, the
      immediate downstream substrate of FAK following the adhesion of Calu-1 cells to
      Coll IV. FAK remains phosphorylated during proliferation either on Coll IV or on
      uncoated plates for 72 h, as determined by peroxivanadate treatment. Exposure of
      Calu-1 cells with 60 microM genistein, reduces FAK phosphorylation (7.6 fold) and
      cell proliferation. Extracellular signal regulated kinases (ERKs) were also
      phosphorylated after Coll IV attachment. Disruption of Calu-1 cell cytoskeleton
      integrity by 1-5 muM Cytochalasin D resulted in the inhibition of cell adhesion
      (50% to 75%, p<0.19 - 6.6 x 10(7)) and ERKs phosphorylation (2 fold) without any
      effect on FAK phosphorylation. Protein Kinase C inhibitor, Calphostin C at 100
      and 250 nM concentrations did not block Coll IV induced FAK phosphorylation but
      activated the ERKs in a dose dependent manner. beta1-integrin is essential for
      Coll IV induced FAK activation, but it is not physically associated with FAK as
      determined by immunodetection assay. Collectively, this report defines the
      existence of multiple and potentially parallel Coll IV/beta1-integrin mediated
      signaling events in Calu-1 cells, which involve FAK, ERKs, and PKC.

PMID- 15963259
TI  - Age-dependent changes in Fibroblast growth factor 2 (FGF-2) expression in mouse
      cerebellar neurons.
AB  - Fibroblast growth factor 2 (FGF-2) is a neurotrophic factor that regulates many
      neuronal functions and survival. We have characterised FGF-2 expression
      immunohistochemically in the cerebellum of young (4 months) and old (22 months)
      mice. About half of the population of the granule cells (GC), and all Purkinje
      cells (PC) expressed FGF-2 in all folia of the cerebellum at both ages. FGF-2
      showed differential intracellular localization: predominantly localised to the
      nuclei of GC and present mainly in the cytosol of PC. There was a statistically
      significant (P = 0.0028) reduction in the number of FGF-2-positive GC in the
      cerebella of old (41.3+/-0.91%) compared to young (48.5+/-1.67%) mice, whereas no
      statistically significant age-dependent difference occurred in the number of FGF
      2 positive PC. These results indicate a possible role of FGF-2 in cerebellar
      ageing.

PMID- 15963260
TI  - C-kit immunopositive interstitial cells (Cajal-type) in human myometrium.
AB  - Previous reports describing Cajal-like interstitial cells in human uterus are
      contradictory in terms of c-kit immunoreactivity: either negative (but vimentin
      positive) in pregnant myometrium, or positive, presumably in the endometrium. The
      aim of this study was to verify the existence of human myometrial Cajal-like
      interstitial cells (m-CLIC). Six different, complementary approaches were used:
      1) methylene-blue supravital staining of tissue samples (cryosections), 2)
      methylene blue and Janus green B vital staining (m-CLIC and mitochondrial
      markers, respectively), and 3) extracellular single-unit electrophysiological
      recordings in cell cultures, 4) non-conventional light microscopy on
      glutaraldehyde/osmium fixed, Epon-embedded semi-thin sections (less than 1
      microm) stained with toluidine blue (TSM), 5) transmission electron microscopy
      (TEM), and 6) immunofluorescence (IF). We found m-CLIC in myometrial cryosections
      and in cell cultures. In vitro, m-CLIC represented approximately 7% of the total
      cell number. m-CLIC had 2-3 characteristic processes which were very long
      (approximately 60 microm), very thin (< or =0.5 microm) and moniliform. The
      dilated portions of processes usually accommodated mitochondria. In vitro, m-CLIC
      exhibited spontaneous electrical activity (62.4+/-7.22 mV membrane potentials,
      short duration: 1.197+/-0.04 ms). Moreover, m-CLIC fulfilled the usual TEM
      criteria, the so-called 'gold' or 'platinum' standards (e.g. the presence of
      discontinuous basal lamina, caveolae, endoplasmic reticulum, and close contacts
      between each other, with myocytes, nerve fibers and/or capillaries etc.). IF
      showed that m-CLIC express CD117/c-kit, sometimes associated with CD34, with
      vimentin along their processes. In conclusion, we describe myometrial Cajal-like
      interstitial cells that have affinity for methylene blue and Janus green B vital
      dyes, fulfill (all) TEM criteria, express CD117/c-kit and have spontaneous
      electric activity.

PMID- 15963261
TI  - Characterization of integrin beta6 and thrombospondin-1 double-null mice.
AB  - To identify overlapping and non-overlapping functions for TSP-1 and alphavbeta6,
      we crossed TSP-1-null and beta6-null mice and compared the phenotype of the
      double-null mice with those of wild-type and single-null mice. The double-null
      mice exhibited focal acute and organizing pneumonia that was more severe than the
      wild-type and single-null mice as well as a significantly higher incidence of
      inflammation in tissues other than the lung. The TSP-1-null and beta6-null mice
      exhibited a five to eight-fold increase in granulocyte recruitment to the lung
      three days after exposure to lipopolysaccharide. They also had abnormalities that
      were infrequently observed in the wild-type and single-null mice, including heart
      degeneration (8.35% in wild-type and 28.1% in double-null mice), hyperplasia of
      the glandular of the stomach (2.8% in wild-type and 21.1% in double-null mice)
      and endometrial hyperplasia (0% in wild-type and 38.5% in double-null females).
      Furthermore, the beta6-null and double-null mice displayed a significant
      elevation in benign and malignant cancers. Stomach papillomas, squamous cell
      carcinomas of the ear and stomach, and adenocarcinomas of the lungs,
      vagina/cervix and colon were observed with the highest frequency. These data
      demonstrate that TSP-1 and alphavbeta6 are involved in regulation of the immune
      system and epithelial homeostasis. They also indicate that alphavbeta6 functions
      as a tumor suppressor gene and that activation of TGFbeta by TSP-1 and
      alphavbeta6 contributes to normal tissue architecture and function.

PMID- 15963262
TI  - Tissue arrays as fiducial markers for section alignment in 3-D reconstruction
      technology.
AB  - Combination of conventional histology and the three-dimensional spatial view of
      tissue structures offers new prospects for understanding and diagnosing nature
      and development of human diseases. The essential technical problem related to
      three-dimensional reconstruction in histopathology is represented by the correct
      alignment of serial sections. During the past years several methods have been
      proposed but failed to become popular because of their limits in terms of time
      consume and restricted applicability. We aimed to overcome this problem by
      applying the technology of Tissue Array, thus by positioning adequate fiducial
      markers from specific "donor" blocks into the "recipient" paraffin block of
      interest. Digitized pictures of serially cut sections were aligned according to
      the tissue markers embedded by Tissue Array, and then processed with specific
      softwares for three-dimensional reconstruction. Thirteen models, including fetal
      hearts, breast and thyroid carcinomas, were elaborated. We found the procedure to
      be easy, fast and reproducible. Moreover, by selectively embedding the fiducial
      markers according to specific angles, the Tissue Arrays can be exploited in order
      to establish the distance between sections. This original methodology of
      incorporating Tissue Arrays into paraffin blocks as fiducial markers for three
      dimensional reconstruction has a potential impact on histology for research
      purposes and diagnostic applications.

PMID- 15963263
TI  - How could a chirp be more effective than a louder clock--resonant transfer of
      energy between subthreshold excitation pulses and excitable tissues.
AB  - By definition, electrical resonance of excitable biomembranes reflects their
      remarkable ability to select input signals with preferential frequencies as ones
      that will pass through the chain of information exchange within a coordinated
      organism. This feature is known to be caused and regulated by the voltage
      dependent kinetics of transmembrane ion channels. Knowledge about the resonant
      behavior of excitable cells may prove crucial toward better underpinning those
      essential properties of neurons which make them to function as a highly
      coordinated network. In this work we present novel experimental evidence which
      strongly supports the paradigm of selective communication between excitable
      cells, by no more than efficient transfer of energy which takes place when the
      frequency of subthreshold presynaptic pulses matches the natural, resonant
      frequency of a target excitable tissue. As a possible direct application, our
      novel experimental results prove the functional importance of bursting activity
      of pre-synaptic neurons as an effective physiological mechanism for
      discriminatory communication between neurons.

PMID- 15963264
TI  - Immune responses induced by intranasal imiquimod and implications for
      therapeutics in rhinovirus infections.
AB  - Notwithstanding the progress recently made in immunology and virology, there is
      yet no effective, specific treatment for the common cold. Symptomatic treatment
      is minimally effective. An anecdotal report of rapid clearing of the common cold
      of recent onset after intranasal application of imiquimod in several subjects by
      one of the authors, made us test the hypothesis that this treatment works through
      the secretion of interferon by the nasal mucosa. We decided to do an animal study
      in primates (Indian Macaca Mulata): 5 treatment and 3 control animals were used.
      Imiquimod or placebo was massaged into the nares of the animals and periodic
      samples of post-nasal fluid were taken and measurements for Interferon alpha
      (IFNalpha) and Tumor Necrosis Factor alpha (TNFalpha) were made by ELISA methods,
      and kinetic studies. mRNA IFNalpha was also isolated and analyzed by quantitative
      competitive RT-PCR. The internal standard was constructed to be complementary to
      and compete with oligonucleotide primers and for amplification of target
      sequences. One intranasal application of imiquimod rapidly (1-4 Hours) induced
      high levels of mRNA for IFNalpha, and minimal levels in the control animals.
      Rapid induction of INFalpha, and proportional increase of TNFalpha sustained for
      4 and 6 hours respectively were noted. No adverse reactions to treatment were
      found in macaques during this short period of intranasal imiquimod usage (except
      in one macaque with a short period of lacrimation). No animal had cytotoxic
      effects when examined at 6 hr, 12 hr, 24 hr or 48 hr, except one animal, which
      had an episode of lacrimation for 6 hr post treatment. Thus both safety and
      efficacy of short treatment with imiquimod is proven in this animal model. Proof
      of principle for intranasal treatment of the common cold with imiquimod is shown.
      We think that this work will encourage a number of double blind clinical trials
      to confirm the effectiveness of the intranasal treatment of the common cold with
      imiquimod.

PMID- 15963265
TI  - A two-dimensional electrophoresis preliminary approach to human hepatocarcinoma
      differentiation induced by PPAR-agonists.
AB  - Adopting biochemical and proteomic approaches, we investigated the effect of some
      PPAR-agonists, a new class of differentiating agents, on human hepatocellular
      carcinoma Hep-G2 cell line. Cancer differentiation was assayed by checking
      albumin, transferrin and alpha-fetoprotein synthesis. Cell metabolism was studied
      by NMR spectroscopy of cell culture supernatants and by evaluation of
      mitochondrial respiratory chain enzyme activities. The two dimensional
      electrophoresis approach was employed to analyze modifications in the expression
      of cellular proteins linked to cell phenotype differentiation in the attempt to
      identify potential diagnostic and prognostic biomarkers of hepatocellular
      carcinoma. Results indicate that PPAR-agonists are able to act as differentiating
      inducers in human hepatocellular carcinoma Hep-G2 cell line as well as to inhibit
      mitochondrial respiratory chain Complex I, provoking a selective derangement of
      cellular oxidative metabolism. Lastly, two dimensional electrophoresis showed
      interesting modifications in the pattern of expression of cellular proteins that
      confirm biochemical data (increase in albumin and transferrin, decrease of alpha
      fetoprotein synthesis) and, moreover, emphasize the meaning of these data by the
      increase of spots indicatively ascribed to HSP70 and catalase.

PMID- 15963266
TI  - About the presence of interstitial cells of Cajal outside the musculature of the
      gastrointestinal tract.
AB  - Santiago Ramon y Cajal observed a special cell type that appeared to function as
      endstructures of the intrinsic nervous system in several organs. These cells were
      structurally and functionally further characterized in the gut musculature and
      named interstitial cells of Cajal (ICC). In recent years, interstitial cells have
      been identified in the vasculature, urinary tract, glands and other organs. Their
      morphologies and functions are just beginning to be clarified. It is likely that
      amongst them, subtypes will be discovered that warrant the classification of
      interstitial cells of Cajal. This "point of view" continues the discussion on the
      criteria that should be used to identify ICC outside the musculature of the gut.

PMID- 15963268
TI  - The interstitial cells of Cajal in pancreas.

PMID- 15963269
TI  - Snapshots of mammary gland interstitial cells: methylene-blue vital staining and
      c-kit immunopositivity.
AB  - We show here that methylene-blue supravital staining of specimens from normal
      human mammary gland reveals (selectively) interstitial (stromal) cells, with 2-3
      long (20-80 microm), thin, moniliform processes. Such cells appear c-kit/CD117
      positive, either by immunohistochemistry (IHC) or immunofluorescence (IF). Since
      these features (affinity for methylene blue, c-kit positivity, and characteristic
      processes) define archetypal interstitial cells of Cajal (ICC) in light
      microscopy, our results suggest the existence of Cajal-like cells in the
      interstitium of human normal mammary gland.

PMID- 15963270
TI  - Novel type of interstitial cell (Cajal-like) in human fallopian tube.
AB  - We describe here--presumably for the first time--a Cajal-like type of tubal
      interstitial cells (t-ICC), resembling the archetypal enteric ICC. t-ICC were
      demonstrated in situ and in vitro on fresh preparations (tissue cryosections and
      primary cell cultures) using methylene-blue, crystal-violet, Janus-Green B or
      MitoTracker-Green FM Probe vital stainings. Also, t-ICC were identified in fixed
      specimens by light microscopy (methylene-blue, Giemsa, trichrome stainings,
      Gomori silver-impregnation) or transmission electron microscopy (TEM). The
      positive diagnosis of t-ICC was strengthened by immunohistochemistry (IHC;
      CD117/c-kit+ and other 14 antigens) and immunofluorescence (IF; CD117/c-kit+ and
      other 7 antigens). The spatial density of t-ICC (ampullar-segment cryosections)
      was 100-150 cells/mm2. Non-conventional light microscopy (NCLM) of Epon semithin
      sections revealed a network-like distribution of t-ICC in lamina propria and
      smooth muscle meshwork. t-ICC appeared located beneath of epithelium, in a 10-15
      microm thick 'belt', where 18+/-2% of cells were t-ICC. In the whole lamina
      propria, t-ICC were about 9%, and in muscularis approximately 7%. In toto, t-ICC
      represent ~8% of subepithelial cells, as counted by NCLM. In vitro, t-ICC were
      9.9+/-0.9% of total cell population. TEM showed that the diagnostic 'gold
      standard' (Huizinga et al., 1997) is fulfilled by 'our' t-ICC. However, we
      suggest a 'platinum standard', adding a new defining criterion- characteristic
      cytoplasmic processes (number: 1-5; length: tens of microm; thickness: < or =0.5
      microm; aspect: moniliform; branching: dichotomous; organization: network,
      labyrinthic-system). Quantitatively, the ultrastructural architecture of t-ICC
      is: nucleus, 23.6+/-3.2% of cell volume, with heterochromatin 49.1+/-3.8%;
      mitochondria, 4.8+/-1.7%; rough and smooth endoplasmic-reticulum (1.1+/-0.6%,
      1.0+/-0.2%, respectively); caveolae, 3.4+/-0.5%. We found more caveolae on the
      surface of cell processes versus cell body, as confirmed by IF for caveolins.
      Occasionally, the so-called 'Ca2+-release units' (subplasmalemmal close
      associations of caveolae+endoplasmic reticulum+mitochondria) were detected in the
      dilations of cell processes. Electrophysiological single unit recordings of t-ICC
      in primary cultures indicated sustained spontaneous electrical activity
      (amplitude of membrane potentials: 57.26+/-6.56 mV). Besides the CD117/c-kit
      marker, t-ICC expressed variously CD34, caveolins 1&2, alpha-SMA, S-100,
      vimentin, nestin, desmin, NK-1. t-ICC were negative for: CD68, CD1a, CD62P, NSE,
      GFAP, chromogranin-A, PGP9.5, but IHC showed the possible existence of
      (neuro)endocrine cells in tubal interstitium. We call them 'JF cells'. In
      conclusion, the identification of t-ICC might open the door for understanding
      some tubal functions, e.g. pace-making/peristaltism, secretion (auto-, juxta-
      and/or paracrine), regulation of neurotransmission (nitrergic/purinergic) and
      intercellular signaling, via the very long processes. Furthermore, t-ICC might
      even be uncommitted bipotential progenitor cells.

PMID- 15963271
TI  - Antimicrobial resistance determinants and future control.
AB  - At the beginning of the 21st century, antimicrobial resistance is common, has
      developed against every class of antimicrobial drug, and appears to be spreading
      into new clinical niches. We describe determinants likely to influence the future
      epidemiology and health impact of antimicrobial-resistant infections.
      Understanding these factors will ultimately optimize preventive strategies for an
      unpredictable future.

PMID- 15963272
TI  - Hidden epidemic of macrolide-resistant pneumococci.
AB  - Community-acquired respiratory tract infections (RTIs) account for a substantial
      proportion of outpatient antimicrobial drug prescriptions worldwide. Concern over
      the emergence of multidrug resistance in pneumococci has largely been focused on
      penicillin-resistant Streptococcus pneumoniae. Macrolide antimicrobial drugs have
      been widely used to empirically treat community-acquired RTIs because of their
      efficacy in treating both common and atypical respiratory pathogens, including S.
      pneumoniae. However, increased macrolide use has been associated with a global
      increase in pneumococcal resistance, which is leading to concern over the
      continued clinical efficacy of the macrolides to treat community-acquired RTIs.
      We provide an overview of macrolide-resistant S. pneumoniae and assess the impact
      of this resistance on the empiric treatment of community-acquired RTIs.

PMID- 15963273
TI  - Community-associated methicillin-resistant Staphylococcus aureus in hospital
      nursery and maternity units.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has
      rarely been reported in the hospital setting. We report an outbreak of 7 cases of
      skin and soft tissue infections due to a strain of CA-MRSA. All patients were
      admitted to the labor and delivery, nursery, or maternity units during a 3-week
      period. Genetic fingerprinting showed that the outbreak strain was closely
      related to the USA 400 strain that includes the midwestern strain MW2. All
      isolates contained the staphylococcal chromosome cassette mec type IV. Genes for
      Panton-Valentine leukocidin and staphylococcal enterotoxin K were detected in all
      isolates, and most contained other enterotoxin genes. Testing of nearly 2,000
      MRSA isolates collected during citywide surveillance studies from 1999 to 2003
      showed that approximate, equals 1% were genetically related to MW2. CA-MRSA
      strain MW2 has been present in this region at least since 1999. This study
      documents the spread of this strain among healthy newborns at 1 hospital.

PMID- 15963274
TI  - Relative fitness of fluoroquinolone-resistant Streptococcus pneumoniae.
AB  - Fluoroquinolone resistance in Streptococcus pneumoniae is primarily mediated by
      point mutations in the quinolone resistance-determining regions of gyrA and parC.
      Antimicrobial resistance mutations in housekeeping genes often decrease fitness
      of microorganisms. To investigate the fitness of quinolone-resistant S.
      pneumoniae (QRSP), the relative growth efficiencies of 2 isogenic QRSP double
      mutants were compared with that of their fluoroquinolone-susceptible parent,
      EF3030, by using murine nasopharyngeal colonization and pneumonia models. Strains
      containing the GyrA: Ser81Phe, ParC: Ser79Phe double mutations, which are
      frequently seen in clinical QRSP, competed poorly with EF3030 in competitive
      colonization or competitive lung infections. However, they efficiently produced
      lung infection even in the absence of EF3030. The strain containing the GyrA:
      Ser81Phe, ParC: Ser79Tyr double mutations, which is seen more frequently in
      laboratory-derived QRSP than in clinical QRSP, demonstrated reduced nasal
      colonization in competitive or noncompetitive lung infections. However, the
      strain was equally able to cause competitive or noncompetitive lung infections as
      well as EF3030.

PMID- 15963275
TI  - Global spread of vancomycin-resistant Enterococcus faecium from distinct
      nosocomial genetic complex.
AB  - Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide,
      and the vancomycin-resistance gene (vanA) has crossed genus boundaries to
      methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents
      an immediate threat for patient care and creates a reservoir of mobile resistance
      genes for other, more virulent pathogens. Evolutionary genetics, population
      structure, and geographic distribution of 411 VRE and vancomycin-susceptible
      Enterococcus faecium isolates, recovered from human and nonhuman sources and
      community and hospital reservoirs in 5 continents, identified a genetic lineage
      of E. faecium (complex-17) that has spread globally. This lineage is
      characterized by 1) ampicillin resistance, 2) a pathogenicity island, and 3) an
      association with hospital outbreaks. Complex-17 is an example of cumulative
      evolutionary processes that improved the relative fitness of bacteria in hospital
      environments. Preventing further spread of this epidemic E. faecium subpopulation
      is critical, and efforts should focus on the early disclosure of ampicillin
      resistant complex-17 strains.

PMID- 15963276
TI  - Community prescribing and resistant Streptococcus pneumoniae.
AB  - We investigated the association between prescribing antimicrobial agents and
      antimicrobial resistance of Streptococcus pneumoniae among children with acute
      otitis media in southern Israel. During a 6-year period, all prescriptions of a
      sample of approximately 20% of Jewish and Bedouin children <5 years of age were
      recorded and all pneumococcal isolates from middle ear fluid were collected.
      Although antimicrobial drug use was significantly higher in Bedouin children, the
      proportion of S. pneumoniae isolates with penicillin MIC = or > 1.0 microg/mL was
      significantly higher in Jewish children. In both populations, antimicrobial
      prescriptions were markedly reduced over time, especially for penicillins and
      erythromycin. In contrast, azithromycin prescriptions increased from 1998 to 2001
      with a parallel increase in macrolide and multidrug resistance. Penicillin
      resistance was associated with macrolide resistance. These findings strongly
      suggest that azithromycin affects increased antimicrobial resistance, including
      multidrug resistance, in S. pneumoniae.

PMID- 15963277
TI  - pVir and bloody diarrhea in Campylobacter jejuni enteritis.
AB  - The plasmid pVir may play a role in the virulence of Campylobacter jejuni, a
      leading cause of bacterial gastroenteritis. The pVir plasmid was identified in
      17% of 104 C. jejuni clinical isolates studied and was significantly associated
      with the occurrence of blood in patient stool, a marker of invasive infection.
      The pVir plasmid was not associated with greater occurrence of diarrhea, fever,
      pain, vomiting, or need for patient hospitalization. Isolates containing pVir
      were also associated with the presence of a tetracycline-resistance plasmid, but
      pVir did not transfer with tetracycline-resistance plasmids to recipient strains
      of C. jejuni. The association of pVir and bloody stool suggests that pVir may be
      clinically relevant in C. jejuni infections.

PMID- 15963278
TI  - Community-associated methicillin-resistant Staphylococcus aureus, Canada.
AB  - A total of 184 methicillin-resistant Staphylococcus aureus (MRSA) strains were
      collected from patients who sought treatment primarily for skin and soft tissue
      infections from January 1, 1999, to March 31, 2002, in east-central Saskatchewan,
      Canada. Molecular subtyping analysis using pulsed-field gel electrophoresis
      showed 2 major clusters. Cluster A (n = 55) was composed of a multidrug-resistant
      MRSA strain associated with a long-term care facility and was similar to the
      previously reported nosocomial Canadian epidemic strain labeled CMRSA-2. Cluster
      B (n = 125) was associated with cases identified at community health centers and
      was indistinguishable from a community-associated (CA)-MRSA strain identified
      previously in the United States (USA400). Cluster B remained susceptible to a
      number of classes of antimicrobial agents and harbored the lukF-PV and lukS-PV
      toxin genes. Over 50% of both clonal groups displayed high-level resistance to
      mupirocin. This is the first report of the USA400 strain harboring the lukF-PV
      and lukS-PV toxin genes in Canada.

PMID- 15963279
TI  - Emergence and spread of Streptococcus pneumoniae with erm(B) and mef(A)
      resistance.
AB  - Streptococcus pneumoniae isolates (N = 31,001) were collected from patients with
      community-acquired respiratory tract infections during the PROTEKT US
      surveillance study (2000-2003). While the macrolide (erythromycin) resistance
      rate remained stable at approximately 29%, the prevalence of resistant isolates
      containing both erm(B) and mef(A) increased from 9.7% in year 1 to 16.4% in year
      3, with substantial regional variability. Almost all (99.2%) dual erm(B) + mef(A)
      macrolide-resistant isolates exhibited multidrug resistance, whereas 98.6% and
      99.0% were levofloxacin- and telithromycin-susceptible, respectively. These
      strains were most commonly isolated from the ear or middle-ear fluid of children.
      Of 152 representative erm(B)+mef(A) isolates, >90% were clonally related to the
      multidrug-resistant international Taiwan19F-14 clonal complex 271 (CC271). Of 366
      erm(B)+mef(A) isolates from the PROTEKT global study (1999-2003), 83.3% were
      CC271, with the highest prevalence seen in South Africa, South Korea, and the
      United States. This study confirms the increasing global emergence and rapidly
      increasing US prevalence of this multidrug-resistant pneumococcal clone.

PMID- 15963280
TI  - International Salmonella Typhimurium DT104 infections, 1992-2001.
AB  - The incidence of multidrug-resistant (MDR) Salmonella Typhimurium infections in
      humans, and in particular MDR definitive phage type 104 (DT104), has increased
      substantially in many countries in the last 2 decades, often associated with
      increased illness. To examine the magnitude of this problem, a survey was
      conducted among countries with available antimicrobial resistance or phage typing
      surveillance data. A total of 29, primarily industrialized, countries
      participated in the survey, which covered the years 1992-2001. Overall, the
      incidence of MDR S. Typhimurium and DT104 increased continuously during this
      period, although the problem affected primarily Europe and North America. The
      increase appeared to have peaked in the United Kingdom but not in other
      countries. Also, the incidence of quinolone-resistant S. Typhimurium was
      increasing. This survey implies that MDR S. Typhimurium constitutes an increasing
      public health problem in large parts of the world and emphasizes the importance
      of surveillance and control programs.

PMID- 15963281
TI  - Methicillin-resistant-Staphylococcus aureus hospitalizations, United States.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly a cause of
      nosocomial and community-onset infection with unknown national scope and
      magnitude. We used the National Hospital Discharge Survey to calculate the number
      of US hospital discharges listing S. aureus-specific diagnoses, defined as those
      having at least 1 International Classification of Diseases (ICD)-9 code specific
      for S. aureus infection. The number of hospital discharges listing S. aureus
      specific diagnoses was multiplied by the proportion of methicillin resistance for
      each corresponding infection site to determine the number of MRSA infections.
      From 1999 to 2000, an estimated 125,969 hospitalizations with a diagnosis of MRSA
      infection occurred annually, including 31,440 for septicemia, 29,823 for
      pneumonia, and 64,706 for other infections, accounting for 3.95 per 1,000
      hospital discharges. The method used in our analysis may provide a simple way to
      assess trends of the magnitude of MRSA infection nationally.

PMID- 15963282
TI  - Integrating Escherichia coli antimicrobial susceptibility data from multiple
      surveillance programs.
AB  - Collaboration between networks presents opportunities to increase analytical
      power and cross-validate findings. Multivariate analyses of 2 large,
      international datasets (MYSTIC and SENTRY) from the Global Advisory on Antibiotic
      Resistance Data program explored temporal, geographic, and demographic trends in
      Escherichia coli resistance from 1997 to 2001. Elevated rates of
      nonsusceptibility were seen in Latin America, southern Europe, and the western
      Pacific, and lower rates were seen in North America. For most antimicrobial drugs
      considered, nonsusceptibility was higher in isolates from men, older patients,
      and intensive care unit patients. Nonsusceptibility to ciprofloxacin was higher
      in younger patients, rose with time, and was not associated with intensive care
      unit status. In univariate analyses, estimates of nonsusceptibility from MYSTIC
      were consistently higher than those from SENTRY, but these differences
      disappeared in multivariate analyses, which supports the epidemiologic relevance
      of findings from the 2 programs, despite differences in surveillance strategies.

PMID- 15963283
TI  - Nonprescribed antimicrobial drugs in Latino community, South Carolina.
AB  - We investigated in a sample of Latinos the practices of antimicrobial drug
      importation and use of nonprescribed antimicrobial drugs. In interviews conducted
      with 219 adults, we assessed health beliefs and past and present behaviors
      consistent with acquiring antimicrobial drugs without a prescription in the
      United States. Many (30.6%) believed that antimicrobial drugs should be available
      in the United States without a prescription. Furthermore, 16.4% had transported
      nonprescribed antimicrobial drugs into the United States, and 19.2% had acquired
      antimicrobial agents in the United States without a prescription. A stepwise
      logistic regression analysis showed that the best predictors of having acquired
      nonprescribed antimicrobial drugs in the United States were beliefs and behavior
      consistent with limited regulations on such drugs. Many persons within the Latino
      community self-medicate with antimicrobial drugs obtained without a prescription
      both inside and outside the United States, which adds to the reservoir of
      antimicrobial drugs in the United States.

PMID- 15963284
TI  - Fluoroquinolone-resistant Escherichia coli carriage in long-term care facility.
AB  - We conducted a cross-sectional study to determine the prevalence of, and risk
      factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in
      residents in a long-term care facility. FQ-resistant E. coli were identified from
      rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable
      analyses, prior FQ use was the only independent risk factor for FQ-resistant E.
      coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12
      months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified
      clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition
      (7 residents) of FQ-resistant E. coli was documented and was associated with de
      novo colonization with genetically distinct strains. Unlike the case in the
      hospital setting, FQ-resistant E. coli carriage in long-term care facilities is
      associated with clonal spread.

PMID- 15963285
TI  - Methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci
      in rural communities, western United States.
AB  - The impact and prevalence of antimicrobial drug resistance in rural community
      healthcare settings is uncertain. Prospective surveillance in 51 rural hospitals
      in Idaho and Utah examined the epidemiologic features of clinical cases of
      methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant
      enterococci (VRE). Thirty-two cases of VRE were reported; for 6, the patient had
      no prior healthcare exposure or coexisting condition. Among the 724 MRSA cases
      available for evaluation, 405 (56%) were healthcare-associated (HA-MRSA), and 319
      (44%) were community-associated (CA-MRSA). The characteristics of HA-MRSA and CA
      MRSA patients with coexisting factors were similar, which suggests community
      transmission of healthcare strains. CA-MRSA cases without coexisting factors,
      however, demonstrated features previously reported for community strains. MRSA
      infections were substantially more frequent than VRE in rural communities in the
      western United States. Based on epidemiologic criteria, a large proportion of
      MRSA cases were community-associated. CA-MRSA rates were predictive of
      institutional MRSA rates.

PMID- 15963286
TI  - Clinician knowledge and beliefs after statewide program to promote appropriate
      antimicrobial drug use.
AB  - In 1999, Wisconsin initiated an educational campaign for primary care clinicians
      and the public to promote judicious antimicrobial drug use. We evaluated its
      impact on clinician knowledge and beliefs; Minnesota served as a control state.
      Results of pre- (1999) and post- (2002) campaign questionnaires indicated that
      Wisconsin clinicians perceived a significant decline in the proportion of
      patients requesting antimicrobial drugs (50% in 1999 to 30% in 2002; p<0.001) and
      in antimicrobial drug requests from parents for children (25% in 1999 to 20% in
      2002; p = 0.004). Wisconsin clinicians were less influenced by nonpredictive
      clinical findings (purulent nasal discharge [p = 0.044], productive cough [p =
      0.010]) in terms of antimicrobial drug prescribing. In 2002, clinicians from both
      states were less likely to recommend antimicrobial agent treatment for the adult
      case scenarios of viral respiratory illness. For the comparable pediatric case
      scenarios, only Wisconsin clinicians improved significantly from 1999 to 2002.
      Although clinicians in both states improved on several survey responses, greater
      overall improvement occurred in Wisconsin.

PMID- 15963287
TI  - Impact of statewide program to promote appropriate antimicrobial drug use.
AB  - The Wisconsin Antibiotic Resistance Network (WARN) was launched in 1999 to
      educate physicians and the public about judicious antimicrobial drug use. Public
      education included radio and television advertisements, posters, pamphlets, and
      presentations at childcare centers. Physician education included mailings,
      susceptibility reports, practice guidelines, satellite conferences, and
      presentations. We analyzed antimicrobial prescribing data for primary care
      physicians in Wisconsin and Minnesota (control state). Antimicrobial prescribing
      declined 19.8% in Minnesota and 20.4% in Wisconsin from 1998 to 2003. Prescribing
      by internists declined significantly more in Wisconsin than Minnesota, but the
      opposite was true for pediatricians. We conclude that the secular trend of
      declining antimicrobial drug use continued through 2003, but a large-scale
      educational program did not generate greater reductions in Wisconsin despite
      improved knowledge. State and local organizations should consider a balanced
      approach that includes limited statewide educational activities with increasing
      emphasis on local, provider-level interventions and policy development to promote
      careful antimicrobial drug use.

PMID- 15963288
TI  - Trypanosomiasis relapse after melarsoprol therapy, Democratic Republic of Congo,
      1982-2001.
AB  - Recently, a high proportion of patients with late-stage Trypanosoma brucei
      gambiense trypanosomiasis, who had been treated with melarsoprol in some disease
      endemic areas, subsequently relapsed. To determine whether the frequency of
      postmelarsoprol relapses increased over time, we reviewed data from 2,221
      trypanosomiasis patients treated with melarsoprol during this period in Nioki,
      Democratic Republic of Congo, from 1982 to 2001. The frequency of relapses was
      5.6%(31/553), 6.8%(35/512), 4.5%(18/398), 11.4%(34/299), and 5.0%(17/343) for
      those treated from 1982 to 1985, 1986 to 1989, 1990 to 1993, 1994 to 1997, and
      1998 to 2001, respectively. The higher frequency of relapses in 1994 to 1997 was
      associated with an incremental dosage regimen of melarsoprol. In multivariate
      analysis, after adjustment for treatment regimen, sex, residence, and
      trypanosomes in cerebrospinal fluid, postmelarsoprol relapses did not increase in
      Nioki, perhaps because 1) little drug pressure exists; 2) subtherapeutic doses
      have rarely been administered; 3) little potential exists for the preferential
      transmission of melarsoprol-resistant strains.

PMID- 15963289
TI  - Methicillin-resistant Staphylococcus aureus in community-acquired skin
      infections.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (MRSA) is the
      most common pathogen among patients with skin and soft tissue infections seeking
      treatment at a Los Angeles (USA) area emergency department. The proportion caused
      by MRSA increased from 29% in 2001 to 2002 to 64% in 2003 to 2004. No clinical or
      historical features reliably predict MRSA etiology.

PMID- 15963290
TI  - Rifampicin resistance in tuberculosis outbreak, London, England.
AB  - Mycobacterium tuberculosis isolates cultured from 6 patients associated with an
      isoniazid-resistant M. tuberculosis outbreak acquired rifampicin resistance. The
      rpoB gene sequence showed that resistance was associated with rare mutations in
      each isolate. Three isolates had a mutation outside the rifampicin resistance
      determining region.

PMID- 15963291
TI  - Free-living Canada geese and antimicrobial resistance.
AB  - We describe antimicrobial resistance among Escherichia coli isolated from free
      living Canada Geese in Georgia and North Carolina (USA). Resistance patterns are
      compared to those reported by the National Antimicrobial Resistance Monitoring
      System. Canada Geese may be vectors of antimicrobial resistance and resistance
      genes in agricultural environments.

PMID- 15963292
TI  - Macrolide- and telithromycin-resistant Streptococcus pyogenes, Belgium, 1999
      2003.
AB  - We found a 13% macrolide resistance in 3,866 Streptococcus pyogenes isolated from
      tonsillopharyngitis patients; 59% macrolide-resistant isolates were distributed
      in 5 clones, suggesting the importance of both resistance gene transfer and
      clonal dissemination in the spread of these organisms. We also report one of the
      largest collections of telithromycin-resistant isolates.

PMID- 15963293
TI  - Hospitalization and antimicrobial resistance in Salmonella outbreaks, 1984-2002.
AB  - Few studies have evaluated the health consequences of antimicrobial-resistant
      Salmonella strains associated with outbreaks. Among 32 outbreaks occurring in the
      United States from 1984 to 2002, 22% of 13,286 persons in 10 Salmonella-resistant
      outbreaks were hospitalized, compared with 8% of 2,194 persons in 22 outbreaks
      caused by pansusceptible Salmonella strains (p<0.01).

PMID- 15963294
TI  - Cephalosporin and ciprofloxacin resistance in Salmonella, Taiwan.
AB  - We report the prevalence and characteristics of Salmonella strains resistant to
      ciprofloxacin and extended-spectrum cephalosporins in Taiwan from January to May
      2004. All isolates resistant to extended-spectrum cephalosporins carried blaCMY
      2, and all ciprofloxacin-resistant Salmonella enterica serotype Choleraesuis
      isolates were genetically related.

PMID- 15963295
TI  - Global spread of multiple aminoglycoside resistance genes.
AB  - Emergence of the newly identified 16S rRNA methylases RmtA, RmtB, and ArmA in
      pathogenic gram-negative bacilli has been a growing concern. ArmA, which had been
      identified exclusively in Europe, was also found in several gram-negative
      pathogenic bacilli isolated in Japan, suggesting global dissemination of
      hazardous multiple aminoglycoside resistance genes.

PMID- 15963296
TI  - armA and aminoglycoside resistance in Escherichia coli.
AB  - We report armA in an Escherichia coli pig isolate from Spain. The resistance gene
      was borne by self-transferable IncN plasmid pMUR050. Molecular analysis of the
      plasmid and of the armA locus confirmed the spread of this resistance
      determinant.

PMID- 15963297
TI  - Tuberculosis due to resistant Haarlem strain, Tunisia.
AB  - Multidrug-resistant tuberculosis was diagnosed in 21 HIV-negative,
      nonhospitalized male patients residing in northern Tunisia. A detailed
      investigation showed accelerated transmission of a Mycobacterium tuberculosis
      clone of the Haarlem type in 90% of all patients. This finding highlights the
      epidemic potential of this prevalent genotype.

PMID- 15963298
TI  - Community-associated methicillin-resistant Staphylococcus aureus, Switzerland.
AB  - Two case-control studies evaluated the prevalence of community-associated
      methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage at hospital
      admission and characteristics of patients with CA-MRSA. Among 14,253 patients, CA
      MRSA prevalence was 0.9/1,000 admissions. Although 5 CA-MRSA isolates contained
      Panton-Valentine leukocidin, only 1 patient had a previous skin infection. No
      easily modifiable risk factor for CA-MRSA was identified.

PMID- 15963299
TI  - Community-associated methicillin-resistant Staphylococcus aureus in pediatric
      patients.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections increased from 2000 to 2003 in hospitalized pediatric patients in
      Houston. CA-MRSA was associated with greater illness than was infection with
      methicillin-susceptible strains. Children with CA-MRSA were younger and mostly
      African American. Of MRSA isolates, 4.5% had the inducible macrolide-lincosamide
      streptogramin B phenotype.

PMID- 15963300
TI  - Erythromycin-nonsusceptible Streptococcus pneumoniae in children, 1999-2001.
AB  - After increasing from 1995 to 1999, invasive erythromycin-nonsusceptible
      Streptococcus pneumoniae rates per 100,000 decreased 53.6% in children from
      Baltimore, Maryland (US), from 1999 to 2001, which was partially attributed to
      strains related to the mefE-carrying England14-9 clone. The decline in infection
      rates was likely due to the pneumococcal 7-valent conjugate vaccine.

PMID- 15963301
TI  - Community-acquired methicillin-resistant Staphylococcus aureus, Uruguay.
AB  - A novel, methicillin-resistant [corrected] Staphylococcus aureus clone (Uruguay
      clone) with a non-multidrug-resistant phenotype caused a large outbreak,
      including 7 deaths, in Montevideo, Uruguay. The clone was distinct from the
      highly virulent community clone represented by strain MW2, although both clones
      carried Panton-Valentine leukocidin gene and cna gene.

PMID- 15963302
TI  - Rifampin-resistant meningococcal disease.
AB  - Rifampin-resistant meningococcal disease occurred in a child who had completed
      rifampin chemoprophylaxis for exposure to a sibling with meningococcemia.
      Susceptibility testing of 331 case isolates found only 1 other case of rifampin
      resistant disease in Minnesota, USA, during 11 years of statewide surveillance.
      Point mutations in the RNA polymerase Beta subunit (rpoB) gene were found in
      isolates from each rifampin-resistant case-patient.

PMID- 15963304
TI  - Data needs and uses for older adult health surveillance: perspectives from state
      health agencies.

PMID- 15963305
TI  - Aging well: toward a way of life for all people.

PMID- 15963306
TI  - Are older adults up-to-date with cancer screening and vaccinations?
AB  - INTRODUCTION: Public health organizations in the United States emphasize the
      importance of providing routine screening for breast cancer, cervical cancer, and
      colorectal cancer, as well as vaccinations against influenza and pneumococcal
      disease among older adults. We report a composite measure of adults aged 50 years
      and older who receive recommended cancer screening services and vaccinations.
      METHODS: We analyzed state data from the 2002 Behavioral Risk Factor Surveillance
      System, which included 105,860 respondents aged 50 and older. We created a
      composite measure that included colonoscopy or sigmoidoscopy within 10 years or a
      fecal occult blood test in the past year, an influenza vaccination in the past
      year, a Papanicolaou test within 3 years for women with an intact cervix, a
      mammogram, and for adults aged 65 and older, a pneumonia vaccination during their
      lifetime. We performed separate analyses for four age and sex groups: men aged 50
      to 64, women aged 50 to 64, men aged 65 and older, and women aged 65 and older.
      RESULTS: The percentage of each age and sex group that was up-to-date according
      to our composite measure ranged from 21.1% of women aged 50 to 64 (four tests) to
      39.6% of men aged 65 and older (three tests). For each group, results varied by
      income, education, race/ethnicity, insurance status, and whether the respondent
      had a personal physician. CONCLUSION: These results suggest the need to improve
      the delivery of cancer screenings and vaccinations among adults aged 50 and
      older. We propose continued efforts to measure use of clinical preventive
      services.

PMID- 15963308
TI  - Computations of confidence intervals for estimates in the United States National
      Hospital Discharge Survey, 1979-2000.
AB  - INTRODUCTION: The National Hospital Discharge Survey is a primary data source for
      epidemiology research in the United States. To ensure that estimates are
      reliable, confidence intervals need to be calculated. The original survey data
      source is not available to the public, and the usual statistical methods are
      unsuitable for calculating confidence intervals. Instead, calculating confidence
      intervals requires using the statistical methods and relative standard errors
      that the U.S. National Center for Health Statistics has provided. However, the
      relative standard error parameters differ by hospital, patient category, and
      group. They also change yearly with sampling and are expressed differently before
      and during or after 1988. Consequently, manual computations of confidence
      intervals with multiple groups, diseases, and years are inefficient and prone to
      error. We developed a SAS program to compute confidence intervals for National
      Hospital Discharge Survey data from 1979 through 2000, newborns excluded.
      METHODS: We transposed 22 tables of relative standard error parameters (one for
      each year) into two new parameter tables that maintain the sampling designs
      before 1988 and during and after 1988 but are similar in overall structure. We
      unified all values to make each set of relative standard error parameters unique.
      We developed a program, COMPURSE, to search for relative standard error
      parameters for inputted estimates and to calculate confidence intervals. We set
      up an interface program for users to enter data, time period, confidence interval
      level, and output location; to read the relative standard error parameter tables;
      and to run the COMPURSE program. RESULTS: For different sets of National Hospital
      Discharge Survey data, COMPURSE efficiently and correctly retrieved relevant
      relative standard error parameters for estimates and accurately calculated
      relative standard errors, standard errors, and confidence intervals for annual
      estimates, multiple-year summaries, and average annual estimates. CONCLUSION: The
      program COMPURSE helps users analyze National Hospital Discharge Survey data
      efficiently.

PMID- 15963307
TI  - Cholesterol levels and statin use in patients with coronary heart disease treated
      in primary care settings.
AB  - INTRODUCTION: Therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA)
      reductase inhibitors, or statins, has proven to be effective in the treatment of
      lipid disorders. However, statin therapy continues to be underused, even though
      statins are a relatively safe and well-tolerated class of agents. In this study,
      we assessed trends in lipid control in patients with heart disease who receive
      most of their health care in primary care clinics. The objective was to determine
      whether systems of care implemented within a large medical group are associated
      with improved treatment and control of dyslipidemia in a high-risk group of
      coronary heart disease patients. METHODS: All adults with heart disease in a
      Minnesota medical group (N = 2947) were identified using diagnosis and procedure
      codes related to coronary heart disease (sensitivity = 0.85; positive predictive
      value = 0.89) in 1996. Study subjects were observed from 1995 to 1998. Subjects
      had a baseline and follow-up test for low-density lipoprotein cholesterol and
      high-density lipoprotein cholesterol. Changes between baseline and follow-up
      measurements and trends in the use of statins and other lipid-active agents among
      the study subjects were analyzed. RESULTS: Among 1388 subjects with two or more
      eligible lipid measurements, mean low-density lipoprotein cholesterol improved
      from 137.6 mg/dL to 111.0 mg/dL (P < .001), and mean high-density lipoprotein
      cholesterol improved from 42.3 mg/dL to 46.3 mg/dL (P < .001). The percentage of
      patients with low-density lipoprotein cholesterol < or = 100 mg/dL rose from
      12.5% to 39.8% (P < .001), and the percentage with high-density lipoprotein
      cholesterol > or = 40 mg/dL rose from 52.5% to 67.6% (P < .001). In multivariate
      models, statin use was identified as the main factor that contributed to the
      improvement in low-density lipoprotein cholesterol (P < .001). Men had greater
      decreases in low-density lipoprotein cholesterol than women after adjusting for
      other variables (P < .001). Statin use rose from 24.3% at baseline to 69.6% at
      follow-up. The statin discontinuation rate was 8.3% for baseline statin users and
      12.2% for subjects who used statins at any time during the study period.
      CONCLUSION: Investment in better heart disease care for patients in primary care
      clinics led to major improvement in lipid control over 30 months, primarily due
      to increased statin use. Improvements in low-density lipoprotein cholesterol and
      high-density lipoprotein cholesterol were sufficient to substantially reduce risk
      of subsequent major cardiovascular events.

PMID- 15963309
TI  - Concordance of chronic conditions in older Mexican American couples.
AB  - INTRODUCTION: There is substantial evidence that marriage is beneficial to
      health, but evidence on whether the health status of one spouse is similar, or
      concordant, with the other spouse is limited. This study assessed whether a
      chronic condition of one spouse is a risk factor for the same chronic condition
      in the other spouse. METHODS: The study used baseline data from the Hispanic
      Established Populations for the Epidemiologic Studies of the Elderly on 553
      couples (1106 individuals) who are representative of approximately 500,000 older
      (> or =65 years) Mexican Americans living in the southwestern United States.
      Logistic regression was used to predict six chronic conditions among couples:
      heart condition, stroke, hypertension, diabetes, arthritis, and cancer. Analyses
      were adjusted for age, education, U.S. nativity, blood pressure, body mass index,
      smoking, and alcohol consumption. RESULTS: The wife's history of hypertension,
      diabetes, arthritis, and cancer was associated with higher odds that the husband
      would have these conditions. A history of hypertension, arthritis, and cancer in
      the husband was associated with higher odds that the wife would have these
      conditions. CONCLUSION: These results provide preliminary evidence that chronic
      conditions in one spouse are associated with an increased risk of developing like
      conditions in the other spouse among older Mexican American couples. We propose
      that the reciprocal influence that marital partners have on each other may be
      caused by shared living arrangements and shared health risks. Health promotion
      activities should target family systems. In particular, health providers should
      gather health histories not only from patients and their genetic family members
      but also from spouses.

PMID- 15963310
TI  - Evaluation of community and organizational characteristics of smoke-free
      ordinance campaigns in 15 Wisconsin cities.
AB  - INTRODUCTION: Smoke-free restaurant ordinance campaigns were conducted in 15
      Wisconsin cities during 1992 through 2002. Community and health coalition
      organizational characteristics varied with each campaign; nine campaigns were
      successful in enacting ordinances, and six campaigns failed. METHODS: Data on
      community and coalition characteristics were analyzed. Community characteristics
      included adjusted gross income, percentage of Democratic voters in recent
      elections, and county smoking prevalence. Coalition characteristics included the
      number of supporters identified, leadership experience, level of print news media
      coverage, and editorial position of local newspaper. RESULTS: Successful
      campaigns were more likely to have leadership with high levels of political
      experience; eight of nine successful campaigns had leadership with high levels of
      experience, and two of six unsuccessful campaigns had leadership with high levels
      of experience. Every successful campaign had high levels of newspaper coverage
      and strong editorial support. None of the unsuccessful campaigns had high levels
      of news coverage or strong editorial support. CONCLUSION: Characteristics
      controlled or influenced by coalitions are associated with successful outcomes.
      Community characteristics were not associated with outcomes. These results should
      assist communities planning to implement smoke-free ordinances or other health
      policy campaigns.

PMID- 15963311
TI  - Evaluation of Salud Para Su Corazon (Health for your Heart) -- National Council
      of La Raza Promotora Outreach Program.
AB  - INTRODUCTION: In 2001, the National Heart, Lung, and Blood Institute partnered
      with the National Council of La Raza to conduct a pilot test of its community
      based outreach program Salud Para Su Corazon (Health for Your Heart), which aims
      to reduce the burden of morbidity and mortality associated with cardiovascular
      disease among Latinos. METHODS: The effectiveness of promotores de salud
      (community health workers) in improving heart-healthy behaviors among Latino
      families participating in the pilot program at seven sites was evaluated. Data on
      the characteristics of the promotores in the Salud Para Su Corazon program were
      compiled. Promotores collected data on family risk factors, health habits,
      referrals and screenings, information sharing, and program satisfaction from 223
      participating Latino families (320 individual family members) through
      questionnaires. Paired t tests and chi-square tests were used to measure pretest
      posttest differences among program participants. RESULTS: Results demonstrated
      the effectiveness of the promotora model in improving heart-healthy behaviors,
      promoting community referrals and screenings, enhancing information sharing
      beyond families, and satisfying participants' expectations of the program. The
      main outcome of interest was the change in heart-healthy behaviors among
      families. CONCLUSION: The community outreach model worked well in the seven pilot
      programs because of the successes of the promotores and the support of the
      community-based organizations. Successes stemmed in part from the train-the
      trainer approach. Promotoria, as implemented in this program, has the potential
      to be integrated with a medical model of patient care for primary, secondary, and
      tertiary prevention.

PMID- 15963312
TI  - The National Program of Cancer Registries: explaining state variations in average
      cost per case reported.
AB  - INTRODUCTION: The Centers for Disease Control and Prevention's National Program
      of Cancer Registries is a federally funded surveillance program that provides
      support and assistance to state and territorial health departments for the
      operation of cancer registries. The objective of this study was to identify
      factors associated with the Centers for Disease Control and Prevention's costs to
      report cancer cases during the first 5 years of the National Program of Cancer
      Registries. METHODS: Information on expenditures and number of cases reported
      through the National Program of Cancer Registries was used to estimate the
      average cost per case reported for each state program. Additional information was
      obtained from other sources, and regression analyses were used to assess the
      contribution of each factor. RESULTS: Average costs of the National Program of
      Cancer Registries differed substantially among programs and were inversely
      associated with the number of cases reported (P < .001). The geographic area of
      the state was positively associated with the cost (P = .01), as was the regional
      cost of living (P = .08), whereas the program type (i.e., enhancement or
      planning) was inversely associated with cost (P = .08). CONCLUSION: The apparent
      existence of economies of scale suggests that contiguous state programs might
      benefit from sharing infrastructure and other fixed costs, such as database
      management resources, depending on the geographic area and population size
      served. Sharing database management resources might also promote uniform data
      collection and quality control practices, reduce the information-sharing burden
      among states, and allow more resources to be used for other cancer prevention and
      control activities.

PMID- 15963313
TI  - The People with Arthritis Can Exercise (PACE) program: a qualitative evaluation
      of participant satisfaction.
AB  - INTRODUCTION: Developed by the Arthritis Foundation, People with Arthritis Can
      Exercise is a community-based exercise program for individuals with arthritis.
      This qualitative study was designed to assess participant satisfaction with the
      program and examine motivators and barriers to attending program classes.
      METHODS: We conducted an 8-week randomized controlled trial of People with
      Arthritis Can Exercise among 347 participants residing in 18 urban and rural
      communities across North Carolina. Semistructured telephone interviews were
      conducted with 51 of the participants. Participants were asked about their
      overall satisfaction with the program. Motivating factors and barriers to
      attending the classes, including content, instructor, location, and schedule,
      were examined. RESULTS: Of the 51 participants interviewed, 96% were female, with
      an average age in years of 67 (range, 32-90 years). Participants reported
      deriving considerable social support from exercising in a group with others who
      have arthritis. They identified two main factors that motivated them to continue
      participating in the exercise class: ability to work at their own pace during the
      class and confidence that they could do different kinds of exercise safely.
      Participants also reported that the instructor played a vital role in sustaining
      their motivation to exercise. Among the participants, noncompleters of the
      program reported arthritis-related illness or insufficient physical challenge as
      key barriers to class participation. CONCLUSION: This study suggests that a group
      exercise program for older adults with arthritis promotes a sense of social
      support and increases self-efficacy for exercise by allowing participants to work
      at their own pace.

PMID- 15963314
TI  - The role of state public health agencies in addressing less prevalent chronic
      conditions.
AB  - INTRODUCTION: State-based chronic disease programs typically focus on the most
      prevalent chronic conditions, such as cancer, diabetes, and cardiovascular
      disease, but interest in less prevalent chronic conditions (LPCCs), such as
      epilepsy, is growing. In our study, we examined the perceived roles of state
      health departments in addressing LPCCs and used this information to develop
      recommendations for state health departments that are considering developing
      LPCCs programs. We also compared the identified state health department roles for
      LPCCs with roles related to healthy aging, as well as to the essential elements
      of existing state-based chronic disease programs, to determine whether future
      LPCCs programs would have any unique requirements. METHODS: Participants used
      concept-mapping techniques to generate a set of 100 statements on steps that
      state health departments could take to address LPCCs. The participants sorted and
      rated each statement according to importance and feasibility. We used a sequence
      of multivariate statistical analyses to generate a series of maps, or clusters,
      and rating graphics. We reviewed the findings and produced recommendations for
      state health departments. We used a similar process to examine roles of state
      health departments in addressing healthy aging. RESULTS: The participants grouped
      the LPCCs statements into nine clusters, which they rated as moderately feasible
      and important. The healthy aging statements were grouped into eight clusters.
      Clusters for LPCCs and healthy aging were similar. We also compared LPCCs
      clusters and the essential elements of existing state-based chronic disease
      programs and found that they were similar. CONCLUSION: The similarities between
      LPCCs clusters and essential elements of existing state-based chronic disease
      programs highlight an important point. State health departments that are
      considering establishing LPCCs programs should use strategies that have already
      been used by other public health agencies to develop chronic disease prevention
      and control programs.

PMID- 15963315
TI  - Sex differences in stroke recovery.
AB  - INTRODUCTION: This study examined differences between men and women in the
      ability to perform basic activities of daily living, instrumental activities of
      daily living, and higher physical functioning after stroke. The objective of the
      study was to determine whether sex differences in stroke recovery can be
      explained by depressive status beyond older age, stroke severity, prestroke
      physical functioning, and other medical comorbidities. METHODS: A total of 459
      stroke patients were recruited from acute and subacute facilities in an urban
      midwestern community. These patients were followed prospectively from stroke
      onset until 6 months poststroke. All study participants were assessed using
      standardized stroke outcome measures, including the National Institutes of Health
      Stroke Scale, the Barthel Activities of Daily Living Index, the Lawton
      Instrumental Activities of Daily Living scale, and the SF-36 Health Survey
      physical functioning scale. The Geriatric Depression Scale was used to assess
      depressive status. Each outcome was measured at baseline (within 2 weeks of
      stroke onset), as well as 1, 3, and 6 months poststroke. Prestroke physical
      functioning, stroke characteristics, and comorbidities were also assessed at
      baseline. RESULTS: Female patients in the study were older than male patients,
      with a mean age of 71 years for women vs 69 years for men. Female patients
      reported lower prestroke physical functioning than their male counterparts. Six
      months after stroke, women in the study were less likely than the men to achieve
      a score of > or = 95 on the Barthel Activities of Daily Living Index (hazards
      ratio [HR] = 0.68; 95% confidence interval [CI], 0.52-0.90), carry out eight of
      nine instrumental activities of daily living without assistance (HR = 0.46; 95%
      CI, 0.30-0.68), and score > or = 90 on the SF-36 Health Survey physical
      functioning scale (HR = 0.54; 95% CI, 0.28-1.01). When age, prestroke physical
      functioning, stroke severity, and depressive status at baseline were controlled
      in the analysis, women in the study continued to be less likely (HR = 0.51; 95%
      CI, 0.32-0.79) than men in the study to be able to carry out eight of nine
      instrumental activities of daily living completely without assistance, but there
      were no observed sex differences in achievement of independence in basic
      activities of daily living or higher physical functioning. CONCLUSION: Prestroke
      physical functioning and depressive symptoms are important factors in the
      investigation of sex differences in stroke recovery. Lower recovery of activities
      of daily living and physical functioning in women after stroke may be due to
      multifactorial effects of older age, poor physical function prior to stroke
      onset, and depressive status after stroke.

PMID- 15963316
TI  - An innovative approach to enhancing the surveillance capacity of state-based
      diabetes prevention and control programs: the Diabetes Indicators and Data
      Sources Internet Tool (DIDIT).
AB  - The Diabetes Indicators and Data Sources Internet Tool (DIDIT) is an interactive
      Web-based resource with information on 38 diabetes indicators (e.g., diabetes
      associated complications, care, lifestyle) and 12 associated data sources
      frequently used by state diabetes prevention and control programs. This tool is
      designed to strengthen the ability of states to conduct diabetes surveillance and
      to promote consistency in defining and tracking indicators across states. In this
      way, the DIDIT supports one of the 10 essential public health services: the
      timely and accurate assessment of public health. In addition to serving as a
      central repository of information on diabetes surveillance, the DIDIT also allows
      users to share experiences of using these indicators and data sources in their
      diabetes surveillance activities, data analysis, and tracking of diabetes-related
      objectives stated by Healthy People 2010. The DIDIT is an innovative approach to
      enhancing public health surveillance at the state and national levels.

PMID- 15963317
TI  - Revisions to chronic disease surveillance indicators, United States, 2004.
AB  - To allow public health officials to uniformly define, collect, and report chronic
      disease data, Indicators for Chronic Disease Surveillance was released by the
      Council of State and Territorial Epidemiologists in 1999. This publication
      provided standard definitions for 73 indicators developed by epidemiologists and
      chronic disease program directors at the state and federal levels. The indicators
      were selected because of their importance to public health and the availability
      of state-level data. This report describes the latest revisions to the chronic
      disease indicators published in 2004. The revised set of 92 indicators includes
      24 for cancer; 15 for cardiovascular disease; 11 for diabetes; 7 for alcohol; 5
      each for nutrition and tobacco; 3 each for oral health, physical activity, and
      renal disease; and 2 each for asthma, osteoporosis, and immunizations. The
      remaining 10 indicators cover such overarching conditions as poverty, education,
      and life expectancy. Although multiple states have used the indicators, wider
      adoption depends on increased epidemiology capacity at the state level and
      improved access to surveillance data.

PMID- 15963318
TI  - Tracking Healthy Days -- a window on the health of older adults.
AB  - In collaboration with its partners in the public health and aging services
      communities, the Centers for Disease Control and Prevention (CDC) Health Care and
      Aging Studies Branch has developed and validated a brief set of health-related
      quality of life (CDC HRQOL) measures for tracking the perceived physical and
      mental health of adults over time. For the past 12 years, these measures -- also
      called the Healthy Days measures -- have been used in an expanding set of
      population health surveys, surveillance systems, performance report cards, and
      evaluation studies, and they have provided useful disease and disability burden
      data to inform decision making and provide new insights for prevention research.
      Although now used continuously to assess health-related quality of life for
      Americans aged 12 years and older, the measures and population data have been
      especially valuable in applications affecting older adults, for which health
      related quality of life is an outcome of primary importance. The CDC HRQOL
      measures are recommended to public health and social service professionals as a
      feasible way to assess perceived physical and mental health needs of older adults
      and to document the effects of policies and interventions.

PMID- 15963321
TI  - Terminology in "Rural community knowledge of stroke warning signs and risk
      factors".

PMID- 15963322
TI  - HIV/AIDS: Here to Stay for a Long Time.

PMID- 15963319
TI  - Age-related eye diseases: an emerging challenge for public health professionals.
AB  - In April 2004, The Eye Disease Prevalence Research Group published a series of
      articles that included age-specific estimates for the prevalence of low vision
      and blindness in whites, African Americans, and Hispanics living in the United
      States. Also included were age-, sex-, and ethnic-specific incidences of the
      following age-related eye diseases: diabetic retinopathy, macular degeneration,
      cataracts, and glaucoma. We reviewed the group's series of articles and
      highlighted key findings on the overall prevalence of and risk factors for age
      related eye diseases, as well as opportunities to preserve and restore vision. We
      examined publications that show the public health impact of age-related eye
      diseases and the importance of projected increases in prevalence of low vision
      and blindness. Approximately 1 in 28 Americans aged older than 40 years is
      affected by low vision or blindness. Among community-dwelling adults, the
      prevalence of low vision and blindness increases dramatically with age in all
      racial and ethnic groups. Whites have higher rates of macular degeneration than
      African Americans, but glaucoma is more common among older African Americans.
      Between 2000 and 2020, the prevalence of blindness is expected to double. Age
      related eye diseases are costly to treat, threaten the ability of older adults to
      live independently, and increase the risk for accidents and falls. To prevent
      vision loss and support rehabilitative services for people with low vision, it is
      imperative for the public health community to address the issue through
      surveillance, public education, and coordination of screening, examination, and
      treatment.

PMID- 15963323
TI  - Evidence-based Medicine and Antibiotic Prophylaxis for Endocarditis: More Fuel to
      the Fire.

PMID- 15963324
TI  - Agents for the Treatment of Multidrug-resistant Gram-positive Endocarditis.
AB  - Several newer agents with activity against multidrug- resistant gram-positive
      pathogens are available. These agents have in vitro and clinical data supporting
      their utility in the treatment of infections caused by pathogens such as
      methicillin-resistant staphylococci and vancomycin-resistant enterococci.
      Daptomycin appears to be rapidly bactericidal, and linezolid and
      quinupristin/dalfopristin also are cidal against staphylococci. Although the
      agents have several properties that are attractive for use in endocarditis,
      clinical data are limited. Further investigation with each agent and combination
      therapy are warranted before definitive recommendations can be made.

PMID- 15963326
TI  - Role of Echocardiography in Diagnosis and Management of Endocarditis.
AB  - Echocardiography plays an increasingly important role in diagnosis and management
      of patients with infective and noninfective endocarditis. Significant changes to
      diagnostic criteria for endocarditis have occurred, and there are evolving trends
      associated with an older population presenting with endocarditis, greater numbers
      of patients with prosthetic heart valves and complex congenital heart disease,
      and an exponential increase in the numbers of patients eligible for pacing and
      defibrillator implants. The diagnostic accuracy of echocardiography has been
      enhanced by developments such as multiplanar transesophageal probes, real-time
      three-dimensional echocardiography, and intracardiac echocardiography. Standard
      echocardiography techniques now define the need for and timing of surgical
      intervention in endocarditis and may help determine the duration of treatment and
      follow-up after diagnosis.

PMID- 15963325
TI  - Dentistry and Endocarditis.
AB  - Bacterial endocarditis (BE), a rare heart infection caused by a bacteremia, has
      frequently been blamed on but rarely caused by dental procedures. Viridans group
      streptococci are found abundantly in the mouth and the gingival sulcus but have
      been surpassed by staphylococci as the leading cause of BE. Antibiotic
      prophylaxis has been recommended before dental procedures in patients at risk for
      BE, but it remains controversial because studies have failed to show that
      antibiotic prophylaxis is an effective preventive for BE or that dental
      procedures are an important cause of BE. The risks and costs of antibiotic
      prophylaxis, including antibiotic resistance, cross-reactions with other drugs,
      allergy, anaphylaxis, and even death, may exceed the benefits in preventing BE.
      The rationale for the use of antibiotic prophylaxis to prevent BE allegedly
      caused by dental procedure bacteremias must be seriously reexamined based on
      recent evidence, particularly the absolute risk rates for endocarditis after a
      given dental procedure.

PMID- 15963327
TI  - Embolic Risk in Subacute Bacterial Endocarditis: Determinants and Role of
      Transesophageal Echocardiography.
AB  - Embolic events are a frequent and life-threatening complication of subacute
      bacterial endocarditis (SBE) and are associated with a high mortality and
      morbidity. The prediction of the embolic risk in an individual patient remains a
      challenge. Echocardiography plays a key role in the management of infective
      endocarditis both for the diagnostic and prognostic assessment of these patients,
      but its value in predicting embolic events is still debated. This review focuses
      on the characteristics of embolic events in SBE, and on the role of
      echocardiography, especially transesophageal echocardiography (TEE), in the
      prediction of embolic events. The review confirms that, among other factors, TEE
      may be helpful in both the prediction of the embolic risk and the decision to
      perform early surgery.

PMID- 15963328
TI  - Dexamethasone for Treatment of Tuberculous Meningitis in Adolescents and Adults.

PMID- 15963329
TI  - Neurosyphilis: A Current Review.
AB  - Neurosyphilis continues to be a difficult diagnosis for clinicians. The decision
      to perform a lumbar puncture, interpretation of cerebrospinal fluid findings,
      clear diagnostic guidelines, establishment of definitive therapy (including
      alternatives to penicillins), and approach to the follow-up of patients with
      neurosyphilis are all areas that pose ongoing challenges to clinicians.
      Coinfection with HIV has also further complicated the already challenging arena
      of neurosyphilis presentation, diagnosis, and management. Clinicians must
      recognize the recent changes in the epidemiology of syphilis and know when to
      initiate appropriate screening. This article highlights the limitations and
      controversies related to neurosyphilis diagnosis and treatment, and current
      recommendations on management of patients with neurosyphilis, including those
      coinfected with HIV.

PMID- 15963330
TI  - Adjunctive Corticosteroids in Adults with Bacterial Meningitis.
AB  - Bacterial meningitis is a complex disorder in which neurologic injury is caused,
      in part, by the causative organism and, in part, by the host's own inflammatory
      response. In studies of experimental bacterial meningitis, adjuvant treatment
      with corticosteroids, specifically dexamethasone, has beneficial effects. On the
      basis of these experimental studies, several clinical trials were undertaken to
      determine the effects of adjunctive corticosteroids in patients with bacterial
      meningitis. On the basis of overall benefit without detrimental effects by
      subgroup analysis, dexamethasone therapy should be initiated before or with the
      first dose of antibiotic and should be continued in most patients with community
      acquired acute bacterial meningitis. For patients with a low suspicion of
      meningitis but an urgent need for antibiotics before cerebrospinal fluid can be
      obtained, we recommend initiation of treatment with dexamethasone, with
      discontinuation of dexamethasone therapy as soon as the diagnosis has been
      excluded.

PMID- 15963331
TI  - West Nile Virus Encephalitis.
AB  - West Nile virus (WNV) is a small RNA virus. It was first isolated in the blood of
      a febrile woman in the West Nile district of Uganda in 1937. Although WNV has
      caused human disease in Africa and Europe since its identification, the first
      documented human infections occurred in the United States in 1999. Wild birds are
      the reservoir for WNV, and most transmission to humans occurs after the bite of
      an infected mosquito. In humans, 80% of infections are asymptomatic and nearly
      20% cause a mild self-limiting illness called WNV fever. Less than 1% will
      develop central nervous system (CNS) infection, which manifests as meningitis,
      encephalitis, or acute flaccid paralysis. The case fatality rate for CNS
      infection is approximately 15%. Human vaccine is not available. Personal mosquito
      protection remains the best prevention, and treatment is supportive.

PMID- 15963332
TI  - Update on Hepatitis B and C Coinfection in HIV.
AB  - Coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) is common in
      patients with HIV infection. HIV infection and immunosuppression alter the
      natural history of chronic viral hepatitis, and some patients experience
      accelerated progression to clinically significant liver disease. Therapies used
      in the treatment of HBV or HCV monoinfection have been applied to the treatment
      of HIV-coinfected patients. However, development of viral resistance and lack of
      virologic response remain significant areas of concern. Timely diagnosis and
      clinical staging of chronic hepatitis infection are critical in the management of
      HIV-coinfected patients.

PMID- 15963333
TI  - Cardiovascular and Endothelial Disease in HIV Infection.
AB  - As combination antiretroviral therapy improves outcome for HIV-infected patients,
      more focus is directed on the durability of these regimens and the prevention of
      long-term adverse events. Given the prevalence of metabolic complications
      associated with combination therapy, namely insulin resistance, dyslipidemia, and
      truncal adiposity, interest in whether these complications predispose patients to
      cardiovascular disease prematurely is appropriate. This paper reviews the most
      recent data regarding the effects of HIV and its treatment on endothelial
      dysfunction, serum biomarkers, and vascular indices, and provides an update on
      the risk for cardiovascular events in the HIV-infected patient population.

PMID- 15963334
TI  - Patterns of lung volume use during an extemporaneous speech task in persons with
      Parkinson disease.
AB  - This study examined patterns of lung volume use in speakers with Parkinson
      disease (PD) during an extemporaneous speaking task. The performance of a control
      group was also examined. Behaviors described are based on acoustic, kinematic and
      linguistic measures. Group differences were found in breath group duration, lung
      volume initiation, and lung volume termination measures. Speakers in the control
      group alternated between a longer and shorter breath groups. With starting lung
      volumes being higher for the longer breath groups and lower for shorter breath
      groups. Speech production was terminated before reaching tidal end expiratory
      level. This pattern was also seen in 4 of 7 speakers with PD. The remaining 3 PD
      speakers initiated speech at low starting lung volumes and continued speaking
      below EEL. This subgroup of PD speakers ended breath groups at agrammatical
      boundaries, whereas control speakers ended at appropriate grammatical boundaries.
      LEARNING OUTCOMES: As a result of participating in this exercise, the reader will
      (1) be able to describe the patterns of lung volume use in speakers with
      Parkinson disease and compare them with those employed by control speakers; and
      (2) obtain information about the influence of speaking task on speech breathing.

PMID- 15963335
TI  - Changes in speech and language development of a young child after decannulation.
AB  - This report reviews the speech and language development of a child who, as result
      of complete subglottic stenosis, was aphonic from birth until 2 years and 11
      months of age at which time laryngotracheal reconstruction provided normal
      respiration. The boy had congenital subglottic stenosis requiring neonatal
      tracheostomy. The congenital subglottic stenosis progressed to complete
      subglottic stenosis during the neonatal period. The child's speech and language
      development was monitored for a 24-week period following airway reconstruction.
      LEARNING OUTCOMES: The reader will learn about and be able to describe: (1) the
      speech and language development of a child who was aphonic from birth until 35
      months of age, (2) the effects of surgical repair of a tracheotomy on the child's
      speech and language development, (3) the likely importance of babbling in speech
      and language development.

PMID- 15963336
TI  - Meaning matters: a clinician's/student's guide to general sign theory and its
      applicability in clinical settings.
AB  - The pragmatic mapping process and its variants have proven effective in second
      language learning and teaching. The goal of this paper is to show that the same
      process applies in teaching and intervention with disordered populations. A
      secondary goal, ultimately more important, is to give clinicians, teachers, and
      other educators a tool-kit, or a framework, from which they can evaluate and
      implement interventions. What is offered is an introduction to a general theory
      of signs and some examples of how it can be applied in treating communication
      disorders. LEARNING OUTCOMES: (1) Readers will be able to relate the three
      theoretical consistency requirements to language teaching and intervention. (2)
      Readers will be introduced to a general theory of signs that provides a basis for
      evaluating and implementing interventions.

PMID- 15963337
TI  - Recent advances in the treatment of stuttering: a theoretical perspective.
AB  - Prolonged speech and its variants are widely used in the behavioral treatment of
      stuttering. Unlike these approaches, which depend on clinician-prescribed speech
      pattern changes, two behavioral treatment regimens, one for children and another
      for adults, recently developed at the Australian Stuttering Research Center,
      promote self-monitoring of speech as a means of controlling stuttering. In these
      programs, the clients themselves modify their speech in subtle and variable ways
      to gain control over stuttering and, in that, they appear to be similar to a well
      known experimental technique for suppressing stutters known as response
      contingent stimulation. The present paper provides an integrated explanation for
      the effectiveness of both clinician-directed as well as client-initiated speech
      pattern modifications and, in the process, develops a new model of stuttering. It
      also shows why client-generated speech patterns changes potentially produce
      faster and more lasting improvement than those changes prescribed by a clinician.
      LEARNING OUTCOMES: The reader will learn about: (1) two hypothesized methods of
      preparing utterance motor plans--speech concatenation and speech construction;
      (2) how behavioral treatment programs make use of speech construction to promote
      fluency in persons who stutter; (3) why therapy procedures based on cognitively
      driven speech construction produce faster and superior results than those based
      on motorically driven speech construction; and (4) the empirical evidence that
      suggests that speech concatenation is the source of stuttering.

PMID- 15963338
TI  - The consequences of spasmodic dysphonia on communication-related quality of life:
      a qualitative study of the insider's experiences.
AB  - The purpose of this study was to explore the biopsychosocial consequences of
      spasmodic dysphonia (SD) as experienced by people with SD. Qualitative research
      methods were used to investigate the insider's perspective of living with SD. Six
      adults with SD participated in face-to-face phenomenological interviews. The
      results are summarized in a model of personal experiences of SD which shows that
      communication-related quality of life (QOL) is shaped by experiences with
      multiple physiologic (voice quality, effort, voice dependability); personal
      (affective responses, changes in self-view, coping strategies) and social
      (physical environment, other people, participation in social roles) factors.
      Communication-related QOL is a complex and individualized construct with
      multidimensional contributors. This study suggests that understanding the nature
      of communication-related QOL for each individual requires exploration of each
      component of the model, exploration of the unique relationships among components
      for each person, and recognition of the multidimensional factors that shape the
      experience of SD. LEARNING OUTCOMES: As a result of this activity the reader will
      be able to (1) identify general features of the phenomenological research method;
      (2) identify the three general categories of psychosocial consequences of SD; (3)
      identify those psychosocial consequences of SD that are under-represented in the
      literature; and (4) identify key conclusions of the communication-related quality
      of life model.

PMID- 15963339
TI  - Selenosugar and trimethylselenonium among urinary Se metabolites: dose- and age
      related changes.
AB  - Once selenium (Se) is absorbed by the body, it is excreted mostly into the urine
      and the major metabolite is 1beta-methylseleno-N-acetyl-d-galactosamine
      (selenosugar) within the required to low-toxic range. Selenosugar plateaus with a
      dose higher than 2.0 microg Se/ml water or g diet, and trimethylselenonium (TMSe)
      starts to increase, indicating that TMSe can be a biomarker of excessive and
      toxic doses of Se. Here, we show dose-related changes in the two urinary Se
      metabolites to clarify the relationship between the dose and urinary metabolites
      by feeding selenite to rats. It was also examined whether the metabolites are
      related to age, and further whether a possible exogenous source of the N-acetyl-d
      galactosamine moiety, chondroitin 4-sulfate, affects the urinary metabolites.
      Selenite in drinking water was fed ad libitum to male Wistar rats of 36 and 5
      weeks of age, and the concentrations of Se in the urine and organs were
      determined together with speciation of the urinary Se metabolites. In young rats,
      selenosugar was always the major urinary metabolite and TMSe increased with a
      dose higher than 2.0 microg Se/ml drinking water. On the other hand, in adult
      rats, TMSe increased only marginally despite that the rats suffered much more
      greatly from the Se toxicity, suggesting that TMSe cannot be a biomarker of Se
      toxicity. The results suggest that sources of the sugar moiety of selenosugar are
      more abundant in adult rats than in young rats. Chondroitin 4-sulfate did not
      affect the ratio of the two urinary metabolites, suggesting that the sugar source
      is of endogenous origin and that it increases with age.

PMID- 15963340
TI  - Involvement of protein kinase C in the mechanism of action of Escherichia coli
      heat-stable enterotoxin (STa) in a human colonic carcinoma cell line, COLO-205.
AB  - The present study was undertaken to determine the involvement of calcium-protein
      kinase C pathway in the mechanism of action of Escherichia coli heat stable
      enterotoxin (STa) apart from STa-induced activation of guanylate cyclase in human
      colonic carcinoma cell line COLO-205, which was used as a model cultured cell
      line to study the mechanism of action of E. coli STa. In response to E. coli STa,
      protein kinase C (PKC) activity was increased in a time-dependent manner with its
      physical translocation from cytosol to membrane. Inhibition of the PKC activity
      in membrane fraction and inhibition of its physical translocation in response to
      IP3-mediated calcium release inhibitor dantrolene suggested the involvement of
      intracellular store depletion in the regulation of PKC activity. Among different
      PKC isoforms, predominant involvement of calcium-dependent protein kinase C
      (PKC(alpha)) was specified using isotype-specific pseudosubstrate, which showed
      pronounce enzyme activity. Inhibition of enzyme activity by PKC(alpha)-specific
      inhibitor Go6976 and immunoblott study employing isotype-specific antibody
      further demonstrated the involvement of calcium-dependent isoform of PKC in the
      mechanism of action of E. coli STa. Moreover, inhibition of guanylate cyclase
      activity by PKC(alpha)-specific inhibitor Go6976 suggested the involvement of
      PKC(alpha) in the regulation of guanylate cyclase activity.

PMID- 15963342
TI  - Comprehensive analysis of differential gene expression profiles on carbon
      tetrachloride-induced rat liver injury and regeneration.
AB  - Microarray analysis of RNA from carbon tetrachloride (CCl4)-administered rat
      livers was performed at various time points to establish a global gene expression
      profile during injury and regeneration stages. A single dose of 1 ml/kg of CCl4
      was given by ip injection, and the liver samples were obtained after 6, 24, 48 h,
      and 2 weeks. Histopathologic, biochemical, and immunohistochemical studies
      enabled the classification of the CCl4 effect into injury (6 and 24 h) and
      regeneration (48 h and 2 weeks) stages. The expression levels of 5180 clones on a
      custom rat gene microarray were analyzed and 587 clones yielded changeable gene
      expression on at least single time point. One hundred seventy-nine clones were
      classified as injury-specific clones, while 38 clones as regeneration-specific
      clones. Characteristic gene expression profiles could be associated with CCl4
      induced gene expression with the disruption of lipid metabolism, which is known
      to cause the fatty liver induced by CCl4 treatment. In addition, induction of the
      transcripts for many ribosomal proteins was detected during the injury stage,
      particularly at the 24-h time point, despite the previous report of decreased
      protein synthesis rate upon CCl4 treatment. Several genes with known functions
      were also identified as CCl4-regulated genes. In conclusion, we established a
      global gene expression profile utilizing microarray analysis in rat liver upon
      acute CCl4 administration with a full chronological profile that not only covers
      injury stage but also later points of regeneration stage.

PMID- 15963341
TI  - Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine
      and chlorpyrifos.
AB  - Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their
      differences in structure and mechanism of action, share many aspects for damage
      to the developing brain. Both are thought to generate oxidative radicals; in the
      current study, we evaluated their ability to produce lipid peroxidation in two in
      vitro models of neural cell development (PC12 and SH-SY5Y cells) and for
      nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos,
      in concentrations relevant to human exposures, elicited an increase in
      thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect
      that was prevented by addition of the antioxidant, Vitamin E. Initiating
      differentiation with nerve growth factor, which enhances nicotinic acetylcholine
      receptor expression, increased the TBARS response to nicotine but not
      chlorpyrifos, suggesting that the two agents act by different originating
      mechanisms to converge on the endpoint of oxidative damage. Furthermore, nicotine
      protected the cells from oxidative damage evoked by chlorpyrifos and similarly
      blocked the antimitotic effect of chlorpyrifos. Treatment of adolescent rats with
      nicotine elicited increases in TBARS in multiple brain regions when given in
      doses that simulate plasma nicotine concentrations found in smokers or at one
      tenth the dose. Our results indicate that nicotine and chlorpyrifos elicit
      oxidative damage to developing neural cells both in vitro and in vivo, a
      mechanism that explains some of the neurodevelopmental endpoints that are common
      to the two agents. The balance between neuroprotectant and neurotoxicant actions
      of nicotine may be particularly important in situations where exposure to tobacco
      smoke is combined with other prooxidant insults.

PMID- 15963343
TI  - Biotransformation and nephrotoxicity of ochratoxin B in rats.
AB  - Ochratoxin B (OTB), a secondary metabolite of Aspergillus ochraceus, is the
      nonchlorinated analogue of the mycotoxin ochratoxin A (OTA), which is one of the
      most potent renal carcinogens in rodents. Despite the closely related structure,
      OTB is considered to be of much lower toxicity. OTA is poorly metabolized and
      slowly eliminated, and this may play an important role in OTA toxicity,
      carcinogenicity, and organ specificity. Since little is known regarding
      biotransformation and renal toxicity of OTB, the aim of this study was to
      investigate biotransformation of OTB in rats and to characterize the
      nephrotoxicity and cytotoxicity of OTB. Male F344 rats were administered either a
      single dose of OTB (10 mg/kg bw) or repeated doses (2 mg/kg bw, 5 days/week for 2
      weeks) and euthanized 72 h after the last dosing. In proximal tubule cells of
      animals treated with a single high dose of OTB, a slight increase in mitotic
      figures was observed, but no treatment-related changes were evident in clinical
      chemistry, in renal function, and histopathology after repeated administration.
      Excretion of OTB and metabolites in urine and feces was analyzed using both HPLC
      with fluorescence detection and LC-MS/MS. Ochratoxin beta, which results from
      cleavage of the peptide bond, was the major metabolite excreted in urine in
      addition to small amounts of 4-hydroxy-OTB. In total, 19% of the administered
      dose was recovered as OTB and ochratoxin beta in urine and feces within 72 h
      after a single dose. In contrast to OTA, no tissue-specific retention of OTB was
      evident after single and repeated administration. In LLC-PK1 cells, a renal cell
      culture system that retains much of the specific features of the proximal tubule,
      only minor differences in the extent of cytotoxicity of OTA and OTB were
      observed. At low concentrations (< 25 microM), treatment with OTA was slightly
      more toxic, whereas reduction in cell viability was similar at concentrations up
      to 100 microM. In summary, these data suggest that OTA and OTB have a similar
      potential to induce cytotoxicity in vitro, but large differences in their
      potential to induce nephrotoxicity in rodents. OTB is more extensively
      metabolized and more rapidly eliminated than OTA. The lack of specific retention
      of OTB in the kidneys and the differences in toxicokinetics may therefore provide
      an explanation for the lower toxicity of OTB.

PMID- 15963344
TI  - Preventive mechanism of cellular glutathione in monomethylarsonic acid-induced
      cytolethality.
AB  - Human pentavalent arsenic metabolic intermediate, monomethylarsonic acid
      (MMAs(V)), is a major arsenic type found in the blood in chronic arsenic
      poisoning patients, but little information is available on its toxicity potential
      or mechanisms of action. In this study, we investigated the molecular mechanisms
      of in vitro cytolethality of MMAs(V) using rat liver TRL 1215 cells. Cellular
      arsenic concentrations reached the nanomolar range in TRL 1215 cells when cells
      were exposed to millimolar levels of MMAs(V), and most of the MMAs(V) was not
      metabolized during the 48-h incubation. Under these conditions, MMAs(V) showed
      significant cytolethality when cellular reserves of reduced glutathione (GSH)
      were depleted. Morphological and biochemical evidence confirmed that MMAs(V)
      induced both necrosis and apoptosis in the cellular GSH-depleted cells. MMAs(V)
      significantly enhanced cellular caspase 3 activity in the cellular GSH-depleted
      cells, and a caspase 3 inhibitor blocked MMAs(V)-induced apoptosis. MMAs(V) also
      enhanced the production of cellular reactive oxygen species (ROS) in the cellular
      GSH-depleted cells, and addition of a membrane-permeable radical trapping reagent
      completely prevented both MMAs(V)-induced cellular caspase 3 activation and
      cytolethality in these cells. These observations suggest that MMAs(V) typically
      generates harmful ROS in cells, and cellular GSH prevents cytolethality by
      scavenging these toxic ROS. However, when cellular GSH levels are decreased,
      MMAs(V) induces oxidative stress in the cells, and this leads to apoptosis and/or
      necrosis depending on the cellular ROS/GSH ratio.

PMID- 15963345
TI  - Arsenite binding to synthetic peptides based on the Zn finger region and the
      estrogen binding region of the human estrogen receptor-alpha.
AB  - We selected the estrogen receptor protein for study because of prior results
      indicating that arsenite is a "potential nonsteroidal environmental estrogen". We
      utilized radioactive (73)As-labeled arsenite and vacuum filtration methodology to
      determine the binding affinity of arsenite to synthetic peptides. A zinc finger
      region containing four free sulfhydryls and the hormone binding region containing
      three free sulfhydryls based on the human estrogen receptor-alpha were studied.
      Peptide 15 (RYCAVCNDYASGYHYGVWSCEGCKA) bound arsenite with a K(d) of 2.2 microM
      and B(max) (maximal binding capacity) of 89 nmol/mg protein. Peptide 10
      (LECAWQGKCVEGTEHLYSMKCKNV) had a K(d) of 1.3 microM and B(max) of 59 nmol/mg
      protein. In contrast, the monothiol peptide 19 (LEGAWQGKGVEGTEHLYSMKCKNV) bound
      arsenite with a higher K(d) of 124 microM and a B(max) of 26 nmol/mg protein. In
      our studies, amino acids other than cysteine (including methionine and histidine)
      did not bind arsenite at all. Peptides modeled on the estrogen receptor with two
      or more nearby free sulfhydryls (two or five intervening amino acids) had low
      K(d) values in the 1-4 microM range. Peptides containing single sulfhydryls or
      two sulfhydryls spaced 17 amino acids apart had higher K(d) values in the 100-200
      microM range, demonstrating lower affinity. With the exception of peptide 24
      which had an unusually high B(max) value of 234 nmol/mg, the binding capacity of
      the studied peptides was proportional to the number of free cysteines. Binding of
      trivalent arsenicals to peptides and proteins can contribute to arsenic toxicity
      and carcinogenicity via altered peptide/protein structure and enzyme function.

PMID- 15963346
TI  - Metabolic activation of polycyclic and heterocyclic aromatic hydrocarbons and DNA
      damage: a review.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic compounds
      (HACs) constitute a major class of chemical carcinogens present in the
      environment. These compounds require activation to electrophilic metabolites to
      exert their mutagenic or carcinogenic effects. There are three principal pathways
      currently proposed for metabolic activation of PAH and HAC: the pathway via bay
      region dihydrodiol epoxide by cytochrome P450 enzymes (CYPs), the pathway via
      radical cation by one-electron oxidation, and the ortho-quinone pathway by
      dihydrodiol dehydrogenase (DD). In addition to these major pathways, a brief
      description of a minor metabolic activation pathway, sulfonation, for PAHs that
      contain a primary benzylic alcoholic group or secondary hydroxyl group(s) is
      included in this review. The DNA damages caused through the reactive metabolites
      of PAH/HAC are described involving the DNA covalent binding to form stable or
      depurinating adducts, the formation of apurinic sites, and the oxidative damage.
      The review emphasizes the chemical/biochemical reactions involved in the
      metabolic processes and the chemical structures of metabolites and DNA adducts.

PMID- 15963347
TI  - More on methyl mercury.

PMID- 15963349
TI  - The 5'-nucleotidases as regulators of nucleotide and drug metabolism.
AB  - The 5'-nucleotidases are a family of enzymes that catalyze the dephosphorylation
      of nucleoside monophosphates and regulate cellular nucleotide and nucleoside
      levels. While the nucleoside kinases responsible for the initial phosphorylation
      of salvaged nucleosides have been well studied, many of the catabolic
      nucleotidases have only recently been cloned and characterized. Aside from
      maintaining balanced ribo- and deoxyribonucleotide pools, substrate cycles that
      are formed with kinase and nucleotidase activities are also likely to regulate
      the activation of nucleoside analogues, a class of anticancer and antiviral
      agents that rely on the nucleoside kinases for phosphorylation to their active
      forms. Both clinical and in vitro studies suggest that an increase in
      nucleotidase activity can inhibit nucleoside analogue activation and result in
      drug resistance. The physiological role of the 5'-nucleotidases will be covered
      in this review, as will the evidence that these enzymes can mediate resistance to
      nucleoside analogues.

PMID- 15963350
TI  - A novel paradigm for therapeutic basis of advanced heart failure--assessment by
      gene therapy.
AB  - The precise mechanism(s) of the progression of advanced heart failure (HF) should
      be determined to establish strategies for its treatment or prevention. Based on
      pathological, molecular, and physiological findings in 3 animal models and human
      cases, we propose a novel scheme that a vicious cycle formed by increased
      sarcolemma (SL) permeability, preferential activation of calpain over
      calpastatin, and translocation and cleavage of dystrophin (Dys) commonly lead to
      advanced HF. The aim of this article was to assess our recent paradigm that
      disruption of myocardial Dys is a final common pathway to advanced HF,
      irrespective of its hereditary or acquired origin, but not intended to provide a
      comprehensive overview of the various factors that may be involved in the course
      of HF in different clinical settings. In addition, each component of Dys
      associated proteins (DAP) was heterogeneously degraded in vivo and in vitro, i.e.
      Dys and alpha-sarcoglycan (SG) were markedly destroyed using isolated calpain 2,
      while delta-SG was not degraded at all. The up-regulation of calpain 2 was
      confirmed through previously published data that remain insufficient for precise
      evaluation, supporting our new scheme that the activation of calpain(s) is
      involved in the steady process of Dys cleavage. In addition, somatic gene therapy
      is discussed as a potential option to ameliorate the physiological/metabolic
      indices and to improve the prognosis.

PMID- 15963352
TI  - The tipsy terminal: presynaptic effects of ethanol.
AB  - Considerable evidence suggests that the synapse is the most sensitive CNS element
      for ethanol effects. Although most alcohol research has focussed on the
      postsynaptic sites of ethanol action, especially regarding interactions with the
      glutamatergic and GABAergic receptors, few such studies have directly addressed
      the possible presynaptic loci of ethanol action, and even fewer describe effects
      on synaptic terminals. Nonetheless, there is burgeoning evidence that presynaptic
      terminals play a major role in ethanol effects. The methods used to verify such
      ethanol actions range from electrophysiological analysis of paired-pulse
      facilitation (PPF) and spontaneous and miniature synaptic potentials to direct
      recording of ion channel activity and transmitter/messenger release from acutely
      isolated synaptic terminals, and microscopic observation of vesicular release,
      with a focus predominantly on GABAergic, glutamatergic, and peptidergic synapses.
      The combined data suggest that acute ethanol administration can both increase and
      decrease the release of these transmitters from synaptic terminals, and more
      recent results suggest that prolonged or chronic ethanol treatment (CET) can also
      alter the function of presynaptic terminals. These new findings suggest that
      future analyses of synaptic effects of ethanol should attempt to ascertain the
      role of presynaptic terminals and their involvement in alcohol's behavioral
      actions. Other future directions should include an assessment of ethanol's
      effects on presynaptic signal transduction linkages and on the molecular
      machinery of transmitter release and exocytosis in general. Such studies could
      lead to the formulation of new treatment strategies for alcohol intoxication,
      alcohol abuse, and alcoholism.

PMID- 15963351
TI  - Physiology and pharmacology of the cardiac pacemaker ("funny") current.
AB  - First described over a quarter of a century ago, the cardiac pacemaker "funny"
      (I(f)) current has been extensively characterized since, and its role in cardiac
      pacemaking has been thoroughly demonstrated. A similar current, termed I(h), was
      later described in different types of neurons, where it has a variety of
      functions and contributes to the control of cell excitability and plasticity.
      I(f) is an inward current activated by both voltage hyperpolarization and
      intracellular cAMP. In the heart, as well as generating spontaneous activity, f
      channels mediate autonomic-dependent modulation of heart rate: beta-adrenergic
      stimulation accelerates, and vagal stimulation slows, cardiac rate by increasing
      and decreasing, respectively, the intracellular cAMP concentration and,
      consequently, the f-channel degree of activation. Four isoforms of
      hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels have been
      cloned more recently and shown to be the molecular correlates of native f
      channels in the heart and h-channels in the brain. Individual HCN isoforms have
      kinetic and modulatory properties which differ quantitatively. A comparison of
      their biophysical properties with those of native pacemaker channels provides
      insight into the molecular basis of the pacemaker current properties and,
      together with immunolabelling and other detection techniques, gives information
      on the pattern of HCN isoform distribution in different tissues. Because of their
      relevance to cardiac pacemaker activity, f-channels are a natural target of drugs
      aimed at the pharmacological control of heart rate. Several agents developed for
      their ability to selectively reduce heart rate act by a specific inhibition of f
      channel function; these substances have a potential for the treatment of diseases
      such as angina and heart failure. In the near future, devices based on the
      delivery of f-channels in situ, or of a cellular source of f-channels (biological
      pacemakers), will likely be developed for use in therapies for diseases of heart
      rhythm with the aim of replacing electronic pacemakers.

PMID- 15963353
TI  - Pharmacological aspects of cytotoxic polyamine analogs and derivatives for cancer
      therapy.
AB  - During the past 20 years, numerous derivatives and analogues of spermidine (Spd)
      and spermine (Spm) were synthesized with the aim to generate a new type of
      anticancer drug. The common denominator of most cytotoxic polyamine analogues is
      their lipophilicity, which is superior to that of the parent amines. The natural
      polyamines bind to polyanions and to proteins with anionic binding sites. Their
      hydrophilicity/hydrophobicity is balanced, allowing them to perform physiological
      functions by interacting with some of these anionic structures, without impairing
      the functionality of others. Because the attachment of lipophilic substituents to
      the polyamine backbone increases the binding energy, lipophilic polyamine
      derivatives affect secondary and tertiary structures of a larger number of
      macromolecules than do their natural counterparts. In addition, lipophilicity
      improves the blood-brain barrier transport and thus enhances CNS toxicity. Close
      structural analogues of spermidine and spermine mimic the natural polyamines in
      regulatory functions. The cytotoxic mechanisms of analogues with a less close
      structural resemblance to spermidine or spermine have not been completely
      clarified. The displacement of spermidine from functional binding sites and the
      consequent prevention of its physiological roles is a likely mechanism, but many
      others may play a role as well. Up to now, polyamine analogues were conceived
      without specific growth-related targets in mind. To develop therapeutically
      useful drugs, it will be imperative to identify specific targets and to design
      compounds that interact selectively with the target molecules. It will also be
      necessary to include, at an early state of the work, pharmacological and
      toxicological considerations, to avoid unproductive directions.

PMID- 15963354
TI  - Therapeutic role of coenzyme Q(10) in Parkinson's disease.
AB  - Mitochondrial dysfunction has been well established to occur in Parkinson's
      disease (PD) and appears to play a role in the pathogenesis of the disorder. A
      key component of the mitochondrial electron transport chain (ETC) is coenzyme
      Q(10), which not only serves as the electron acceptor for complexes I and II of
      the ETC but is also an antioxidant. In addition to being crucial to the
      bioenergetics of the cell, mitochondria play a central role in apoptotic cell
      death through a number of mechanisms, and coenzyme Q(10) can affect certain of
      these processes. Levels of coenzyme Q(10) have been reported to be decreased in
      blood and platelet mitochondria from PD patients. A number of preclinical studies
      in in vitro and in vivo models of PD have demonstrated that coenzyme Q(10) can
      protect the nigrostriatal dopaminergic system. A phase II trial of coenzyme Q(10)
      in patients with early, untreated PD demonstrated a positive trend for coenzyme
      Q(10) to slow progressive disability that occurs in PD.

PMID- 15963355
TI  - Many good reasons to have STAT3 in the heart.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) participates in a wide variety of physiological processes and directs
      seemingly contradictory responses, such as proliferation and apoptosis. The
      constitutive activation of STAT3 promotes tumor growth and angiogenesis and is
      associated with drug resistance in cancer therapy. In contrast, in the heart, the
      down-regulation of STAT3 has been associated with end-stage heart failure in
      patients. Moreover, multiple studies showed that the activation of STAT3 promotes
      cardiomyocyte survival and hypertrophy, as well as cardiac angiogenesis, in
      response to various pathophysiologic stimuli, strongly suggesting that STAT3 is
      beneficial for the heart. Conditional knockout (STAT3-KO) mice harboring a
      cardiomyocyte-restricted deletion of STAT3 showed enhanced susceptibility to
      cardiac injury caused by myocardial ischemia, systemic inflammation, or drug
      toxicity. STAT3-KO mice were also more prone to the pathogenesis of age-related
      heart failure. Thus, STAT3 is involved in multiple mechanisms required for the
      protection of the heart from injury and heart failure. These observations should
      be taken into account in designing novel therapeutic strategies for the
      prevention of cardiac failure.

PMID- 15963356
TI  - Critical periods for the role of oxidative stress in the developmental
      neurotoxicity of chlorpyrifos and terbutaline, alone or in combination.
AB  - The developmental neurotoxicity of chlorpyrifos (CPF) involves mechanisms other
      than inhibition of cholinesterase. In the current study, we examined the ability
      of CPF to evoke lipid peroxidation in the developing brain of fetal and neonatal
      rats. CPF given to pregnant rats on gestational days 17-20 or to neonatal rats on
      postnatal days 1-4, failed to elicit increases in thiobarbituric acid-reactive
      species (TBARS) in brain regions even when the dose was raised above the
      threshold for systemic toxicity and hepatic damage. In contrast, CPF
      administration during the second postnatal week, the peak period of neuronal cell
      differentiation and synaptogenesis, did evoke significant increases in TBARS even
      at a dose devoid of systemic toxicity. Terbutaline, which is chemically unrelated
      to CPF and which stimulates neuronal cell metabolism through direct actions on
      beta-adrenoceptors, also elicited oxidative damage in the developing brain with
      greater sensitivity in the second postnatal week. These results indicate that
      diverse compounds can exert convergent effects on brain development through their
      shared potential to elicit oxidative stress, and that the net outcome is
      dependent upon specific developmental stages in which metabolic demand is
      especially high. Furthermore, given the common use of terbutaline in the therapy
      of preterm labor, and the nearly ubiquitous exposure of the human population to
      organophosphorus pesticides, the combined oxidative burden of exposure to both
      agents may contribute to the worsened neurodevelopmental outcomes noted in animal
      models of such dual exposures.

PMID- 15963357
TI  - A new software for carrying out one-way ANOVA post hoc tests.
AB  - The objective of this study was to develop a convenient, easy to use stand-alone
      program to statistically process experimental data. The method involves user
      input of data for analysis into a grid format, followed by one-way analysis of
      variance (ANOVA) of the data to determine the F ratio. If the value of the F
      ratio is greater than the appropriate critical F distribution at alpha=0.05, the
      null hypothesis is rejected, it is assumed that at least one of the group means
      is significantly different from the other group means, and it is valid to proceed
      with post hoc testing. A choice of four post hoc tests are available: Dunnett's,
      Fisher's, Scheffe's or Tukey's. The results of the post hoc test are displayed
      and can be printed for record keeping. The methodology developed in this present
      study should help scientists to carry out post hoc comparisons quickly and easily
      without the expense or time that commercial statistical packages require.

PMID- 15963358
TI  - A single amino acid substitution improves the in vivo immunogenicity of the HPV16
      oncoprotein E7(11-20) cytotoxic T lymphocyte epitope.
AB  - One of the few and most extensively studied human papilloma virus (HPV) type 16
      oncoprotein E7-derived cytotoxic T lymphocyte (CTL) epitopes is YMLDLQPETT,
      presented to CTL by HLA-A2.1. We previously identified an altered peptide ligand
      (APL) of this epitope with increased binding affinity for HLA-A2.1, YMLDLQPETV.
      Herein, the in vivo immunogenicity of this APL was investigated in HLA-A2.1
      transgenic HHD mice. Both in vitro and direct ex vivo analysis, performed using
      newly generated HHD tetramers, showed a significant increase in the number of
      specific CD8+ T cells upon vaccination with the APL as compared to its unmodified
      counterpart. Improved immunogenicity of the APL was also observed in functional
      analyses, including antigen-specific lytic activity and cytokine production of
      primed CD8+ T cells. Consequently, the YMLDLQPETV peptide may prove useful when
      included in vaccination strategies against HPV16-induced cervical carcinoma.

PMID- 15963359
TI  - Reduced viral burden amongst high responder patients following HIV-1 p24 peptide
      based therapeutic immunization.
AB  - We have previously shown that HIV p24-like peptides (Vacc-4x) via activation of
      skin dendritic cells induced immune responses in 90% of HIV patients on highly
      active antiretroviral treatment (HAART). These patients (n=38) were here
      subjected to a final 14-week interruption of HAART. Patients with the highest
      delayed type hypersensitivity (DTH) responses to Vacc-4x-peptides before
      treatment interruption tended to achieve lower actual HIV RNA levels at the end
      of the study compared to Vacc-4x DTH low-responders (p=0.08) and significantly so
      in terms of viral loads relative to their individual pre-HAART HIV RNA set-points
      (p=0.04). CD4+ lymphocyte counts were maintained only among DTH high responders
      but decreased in the other patients during recurrent viremia (p</=0.02). No other
      pre-study differences in HIV history or p24-responses were found.

PMID- 15963360
TI  - Formulation of botulinum neurotoxin heavy chain fragments for vaccine
      development: mechanisms of adsorption to an aluminum-containing adjuvant.
AB  - Heavy chain fragments of botulinum neurotoxin serotypes A and B are being
      developed as a bivalent vaccine for botulism. To potentiate the immune response,
      an aluminum containing adjuvant will be formulated with the two antigens. The
      adsorption mechanisms of each antigen to aluminum phosphate and aluminum
      hydroxide adjuvants were studied. The adsorption of the serotype A antigen to
      each adjuvant, and the serotype B antigen to aluminum phosphate adjuvant, is
      dependent on electrostatic attractive forces. The serotype A antigen is basic,
      and pretreatment with phosphate anions is required for favorable adsorption
      conditions to aluminum hydroxide adjuvant. In contrast, the serotype B antigen
      displays a high affinity to aluminum hydroxide adjuvant even when the two species
      possess the same charge. It is proposed that the serotype B antigen is adsorbed
      to aluminum hydroxide adjuvant by a ligand exchange mechanism.

PMID- 15963361
TI  - Efficacy of a SHIV 89.6 proviral DNA vaccine against mucosal SIVmac239 challenge.
AB  - Sixty percent of rhesus macaques infected with virulence attenuated virus SHIV
      89.6 are protected from subsequent intravaginal challenge with pathogenic
      SIVmac239 [Abel K, Compton L, Rourke T, Montefiori D, Lu D, Rothaeusler K, et al.
      Simian-human immunodeficiency virus SHIV89.6-induced protection against
      intravaginal challenge with pathogenic SIVmac239 is independent of the route of
      immunization and is associated with a combination of cytotoxic T-lymphocyte and
      alpha interferon responses. J Virol 2003;77(5):3099-118; Miller CJ, McChesney MB,
      Lu X, Dailey PJ, Chutkowski C, Lu D, et al. Rhesus macaques previously infected
      with simian/human immunodeficiency virus (HIV) are protected from vaginal
      challenge with pathogenic SIVmac239. J Virol 1997;71(3):1911-21]. Previously, we
      have shown that inoculation with a proviral plasmid encoding SHIV 89.6 (pMA SHIV
      89.6) results in systemic infection that is delayed compared to SHIV 89.6 virus
      inoculation [Busch M, Lu D, Fritts L, Lifson JD, Miller CJ. Comparison of
      virology and immunology in SHIV 89.6 proviral DNA and virus-inoculated rhesus
      macaques. J Med Primatol 2003;32(4-5):240-6]. We now report that, although
      monkeys inoculated with pMA SHIV-89.6 or SHIV 89.6 virus had similar plasma anti
      SIV binding antibody titers and number of anti-SIV IFN-gamma secreting cells on
      the day of mucosal SIVmac239 challenge, a smaller proportion of monkeys immunized
      with pMA SHIV-89.6 were protected from vaginal SIVmac239 challenge compared to
      monkeys immunized using SHIV 89.6 virus. Protected DNA immunized monkeys had
      stronger anti-SIV IFN-gamma ELISPOT responses in the acute stage post-challenge
      than unprotected monkeys. Plasma anti-SIV binding antibody titers and PBMC
      cytokine responses in the acute stages post-challenge were similar in DNA
      vaccinated-protected and DNA vaccinated-unprotected monkeys. These results
      suggest that the delay in systemic infection resulting from delivery of SHIV 89.6
      as a plasmid decreased the effectiveness of this live attenuated vaccine.

PMID- 15963362
TI  - Pulmonary CD4+ cytokine responses in mice reveal differences in the relative
      immunogenicity of cold-adapted influenza A vaccine donor strains.
AB  - We previously described differences in the 50% protective dose and isotype
      specific antibody secreting cell (ASC) responses to US and Russian influenza A
      cold-adapted (ca) donor strains in the lungs of BALB/c mice [Wareing MD, Watson
      JM, Brooks MJ, Tannock GA. Immunogenic and isotype-specific responses to Russian
      and US cold-adapted influenza A vaccine donor strains A/Leningrad/134/17/57,
      A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice. J Med Virol
      2001;65(1):171-7]. A/Leningrad/134/17/57(Len/17-ca) was shown to be a superior
      immunogen to A/Leningrad/134/47/57-ca (Len/47-ca), which, in turn, was superior
      to A/Ann Arbor/6/60-ca (AA-ca) but no other comparative data exist. In order to
      extend our findings and determine a means for selecting the most immunogenic ca
      influenza A vaccine, the intracellular cytokine responses by CD4+ and CD8+ T
      cells to AA-ca, Len/47-ca and Len/17-ca and their respective wild-type parental
      viruses were compared in mice. Day 5 after infection with Len/17-ca, when levels
      of IL-2, -4 and -10 were highest in the mediastinal lymph nodes (MLN) and lungs,
      was chosen as the optimum time to harvest lymphocytes and 72 h was determined to
      be the optimum re-stimulation period for lymphocytes by APCs. Under these
      conditions, the frequency of CD4+ and CD8+ cells expressing cytokines was highest
      in the lungs compared with the MLN. A dominant IL-6 response was induced,
      although all virus strains induced a Th1/Th2 cytokine profile. While the CD8+
      cytokine response appeared non-specific, the cytokine response elicited in the
      lungs by CD4+ cells to Len/17-ca-inoculation was greater than that induced by
      Len/47-ca, or AA/ca. The CD4+ cytokine response in the lungs may be a useful
      measure of immunogenicity to determine the most effective influenza reassortant
      for inclusion in vaccines.

PMID- 15963363
TI  - Immunogenicity of two paediatric doses of monovalent hepatitis B or combined
      hepatitis A and B vaccine in 8-10-year-old children.
AB  - Hepatitis A and B vaccines are highly immunogenic in three-dose schedules. To
      obtain an equivalent result in children with two paediatric doses would be of
      significant benefit. The purpose of this study was to measure the immunogenicity
      of a two-dose schedule in children with two licensed recombinant HBsAg containing
      vaccines given at paediatric doses, one of them combined with hepatitis A. Seven
      hundred and four healthy school children aged 8-10 years were recruited in an
      open label study to receive either Twinrix Pediatric (360 El.U HAV antigen; 10
      microg HBsAg) or Recombivax (2.5 microg HBsAg) vaccine intramuscularly 6 months
      apart. The seroconversion (>/=1 mIU/ml for anti-HBs antibodies and >/=33 mIU/ml
      for anti-HAV antibodies), seroprotection (anti-HBs >/=10 mIU/ml) rates and the
      geometric mean titers (GMTs) were determined 4-8 weeks after the second dose. The
      anti-HBs seroconversion rate was 97.1% with Twinrix and 97.2% with Recombivax.
      The seroprotection rates were 96.5 and 94.4%, respectively (P = 0.17). The GMT
      was higher with Twinrix than with Recombivax (3248 mIU/ml versus 742 mIU/ml, P <
      0.0001). All the children vaccinated with Twinrix seroconverted to HAV and the
      GMT was 5168 mIU/ml. The obtained results suggest that two paediatric doses of
      hepatitis vaccines are highly immunogenic in 8-10-year-old children. This
      schedule could facilitate a greater vaccine acceptance and the addition of
      hepatitis A vaccine to existing adolescent universal hepatitis B virus
      immunization programs.

PMID- 15963364
TI  - Prophylactic vaccination with phage-displayed epitope of C. albicans elicits
      protective immune responses against systemic candidiasis in C57BL/6 mice.
AB  - Epitope LKVIRK on 47 kDa of heat shock protein (Hsp) 90 of Candida albicans,
      corresponding to residues 386-391 of the Hsp90, is recognized by patients
      recovering from invasive candidiasis. The efficacy of hybrid phage displaying
      epitope LKVIRK in the N-terminal region of the major coat protein (pVIII) in
      inducing anti-invasive candidiasis immune response was studied in C57BL/6 mice.
      Indirect phage-ELISA results demonstrated that the mice immunized with hybrid
      phage had significantly higher titers of epitope LKVIRK-specific serum IgG as
      compared to those immunized with heat-killed C. albicans (HK-CA). C57BL/6 mice
      immunized either with hybrid phage or with wild-type phage also developed
      significant levels of delayed-type hypersensitivity (DTH) response and splenocyte
      proliferation, as well as with HK-CA. In addition, high levels of IFN-gamma in
      the CD4(+) splenocytes from phage-immunized mice were detected as well during 1
      week post-inoculation. Furthermore, mice immunized with hybrid phage acquired a
      resistance to systemic C. albicans infection as confirmed by fewer C. albicans
      cells in the kidneys, and had a longer lifespan compared to control groups
      following intravenous challenge with C. albicans. These results indicate that
      hybrid phage displaying epitope LKVIRK may serve as a potential vaccine
      conferring a resistance to systemic candidiasis.

PMID- 15963365
TI  - Assessment of contaminant lability during phytoremediation of polycyclic aromatic
      hydrocarbon impacted soil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are recalcitrant compounds, some of which
      are known carcinogens, often found in high residual soil concentrations at
      industrial sites. Recent research has confirmed that phytoremediation holds
      promise as a low-cost treatment method for PAH contaminated soil. In this study,
      the lability of soil bound PAHs in the rhizosphere was estimated using solid
      phase extraction resin. An extraction time of 14 days was determined to be
      appropriate for this study. Resin-extractable PAHs, which are assumed to be more
      bioavailable, decreased during plant treatments. Significant reductions in the
      labile concentrations of several PAH compounds occurred over 12 months of plant
      growth. The differences in concentration between the unplanted and the planted
      soil indicate that the presence of plant roots, in addition to the passage of
      time, contributes to reduction in the bioavailability of target PAHs.

PMID- 15963366
TI  - Organotin contamination in fishes with different living patterns and its
      implications for human health risk in Taiwan.
AB  - Contaminated levels of butyl- and phenyltin compounds, tributyltin (TBT),
      dibutyltin (DBT), monobutyltin (MBT), triphenyltin (TPT), diphenlytin (DPT), and
      monophenyltin (MPT), were investigated in pelagic, demersal and cultured fish
      species from different seasons and locations in Taiwan. Seasonal variations were
      found in fishes from Wuchi and Hsingta fishing harbors for their butyltin levels
      (winter>summer) with the opposite trend for phenyltins in fishes from Patoutzu
      fishing harbor and demersal fishes from four fishing harbors (summer>winter).
      Fish liver contained the lowest percentage of TBT and the highest percentage of
      TPT among six organotin compounds. Consumption of contaminated pelagic species
      and fishes from Hsingta fishing harbor had the highest hazard index. However, the
      hazard quotients and hazard indices were all less than 1, suggesting a daily
      exposure at these levels of TBT, DBT and TPT may not be likely to cause any
      deleterious effects during lifetime in human population.

PMID- 15963368
TI  - Temporal variation of trace metal geochemistry in floodplain lake sediment
      subject to dynamic hydrological conditions.
AB  - Climate change and land use may significantly influence metal cycling in dynamic
      river systems. We studied temporal variation of sediment characteristics in a
      floodplain lake, including concentrations of dissolved organic carbon, acid
      volatile sulfide and trace metals. The sampling period included a severe winter
      inundation and a dramatic water level drop during summer. Temporal changes were
      interpreted using multivariate analysis and chemical equilibrium calculations.
      Metal concentrations in sediment increased with depth, indicating a gradual
      improvement of sediment quality. In contrast, dissolved metal concentrations were
      highest in top layers due to mobilization from oxyhydroxides and precipitation
      with sulfides in deeper layers. Inundation had a mobilizing effect as it
      stimulated resuspension and oxygenation of sediment top layers. Water table
      lowering combined with organic matter decomposition led to immobilization due to
      sulfide formation. The chemistry of the sediments was consistent with model
      calculations, especially for macro-elements. The results illustrate the
      importance of seasonality for metal risk assessment.

PMID- 15963367
TI  - The analysis of soil cores polluted with certain metals using the Box-Cox
      transformation.
AB  - To define the soil properties for a given area or country including the level of
      pollution, soil survey and inventory programs are essential tools. Soil data
      transformations enable the expression of the original data on a new scale, more
      suitable for data analysis. In the computer-aided interactive analysis of large
      data files of soil characteristics containing outliers, the diagnostic plots of
      the exploratory data analysis (EDA) often find that the sample distribution is
      systematically skewed or reject sample homogeneity. Under such circumstances the
      original data should be transformed. The Box-Cox transformation improves sample
      symmetry and stabilizes spread. The logarithmic plot of a profile likelihood
      function enables the optimum transformation parameter to be found. Here, a
      proposed procedure for data transformation in univariate data analysis is
      illustrated on a determination of cadmium content in the plough zone of
      agricultural soils. A typical soil pollution survey concerns the determination of
      the elements Be (16 544 values available), Cd (40 317 values), Co (22 176
      values), Cr (40 318 values), Hg (32 344 values), Ni (34 989 values), Pb (40 344
      values), V (20 373 values) and Zn (36 123 values) in large samples.

PMID- 15963369
TI  - Acid neutralization within limestone sand reactors receiving coal mine drainage.
AB  - Pulsed bed treatment of acid mine drainage (AMD) uses CO2 to accelerate limestone
      dissolution and intermittent fluidization to abrade and carry away metal
      hydrolysis products. Tests conducted with a prototype of 60 L/min capacity showed
      effective removal of H+ acidity over the range 196-584 mg/L (CaCO3) while
      concurrently generating surplus acid neutralization capacity. Effluent alkalinity
      (mg/L CaCO3) rose with increases in CO2 (DC, mg/L) according to the model
      Alkalinity=31.22+2.97(DC)0.5, where DC was varied from 11-726 mg/L. Altering
      fluidization and contraction periods from 30s/30s to 10s/50s did not influence
      alkalinity but did increase energy dissipation and bed expansion ratios. Field
      trials with three AMD sources demonstrated the process is capable of raising AMD
      pH above that required for hydrolysis and precipitation of Fe3+ and Al3+ but not
      Fe2+ and Mn2+. Numerical modeling showed CO2 requirements are reduced as AMD
      acidity increases and when DC is recycled from system effluent.

PMID- 15963370
TI  - Sampling technologies and air pollution control devices for gaseous and
      particulate arsenic: a review.
AB  - Direct measurement of arsenic release requires a good sampling and analysis
      procedure in order to capture and detect the total amount of metals emitted. The
      literature is extensively reviewed in order to evaluate the efficiency of full
      field-scale and laboratory scale techniques for capturing particulate and gaseous
      emissions of arsenic from the thermo-chemical treatment of different sources of
      arsenic. Furthermore, trace arsenic concentrations in ambient air, national
      standard sampling methods and arsenic analysis methods are considered. Besides
      sampling techniques, the use of sorbents is also reviewed with respect to both
      approaches (1) to prevent the metals from exiting with the flue gas and (2) to
      react or combine with the metals in order to be collected in air pollution
      control systems. The most important conclusion is that submicron arsenic fumes
      are difficult to control in conventional air pollution control devices. Complete
      capture of the arsenic species requires a combination of particle control and
      vapour control devices.

PMID- 15963372
TI  - Comparison of PM2.5 carbon measurement methods in Hong Kong, China.
AB  - Samples from Hong Kong, China, were analyzed for organic carbon (OC), elemental
      carbon (EC), and total carbon (TC) by three thermal protocols (low-temperature
      IMPROVE and high-temperature STN and NIOSH) and two optical monitoring methods:
      reflectance and transmittance. Good agreement (+/-10%) for TC among the three
      protocols was observed for sample loadings of 1-55 microg m(-3). The two
      protocols using a reflectance pyrolysis correction showed best agreement for EC,
      with <20% differences found for approximately 80% of the samples. Hong Kong has a
      large diesel fleet, and for some heavily loaded samples the light transmittance
      was too low for quantitative detection, resulting in large uncertainties in the
      OC/EC split based on transmittance. Hong Kong experienced OC levels similar to
      those at US sites, but has much higher EC concentrations. OC/EC ratios range from
      2 to 5 at two US sites and from 0.2 to 1.2 at three Hong Kong sites.

PMID- 15963371
TI  - Perfluorooctane sulfonic acid and organohalogen pollutants in liver of three
      freshwater fish species in Flanders (Belgium): relationships with biochemical and
      organismal effects.
AB  - A perfluorooctane sulfonic acid (PFOS) assessment was conducted on gibel carp
      (Carassius auratus gibelio), carp (Cyprinus carpio), and eel (Anguilla anguilla)
      in Flanders (Belgium). The liver PFOS concentrations in fish from the Ieperlee
      canal (Boezinge, 250-9031 ng/g wet weight, respectively) and the Blokkersdijk
      pond (Antwerp, 633-1822 ng/g wet weight) were higher than at the Zuun basin (Sint
      Pieters-Leeuw, 11.2-162 ng/g wet weight) and among the highest in feral fish
      worldwide. Eel from the Oude Maas pond (Dilsen-Stokkem) and Watersportbaan basin
      (Ghent) had PFOS concentrations ranging between 212 and 857 ng/g wet weight. The
      hepatic PFOS concentration was significantly and positively related with the
      serum alanine aminotransferase activity, and negatively with the serum protein
      content in eel and carp. The hepatic PFOS concentration in carp correlated
      significantly and negatively with the serum electrolyte concentrations whereas a
      significant positive relation was found with the hematocrit in eel. Although 13
      organochlorine pesticides, 22 polychlorinated biphenyl (PCB) congeners and 7
      polybrominated diphenyl ethers (PBDEs) were also measured in the liver tissue,
      only PCB 28, PCB 74, gamma-hexachlorocyclohexane (gamma-HCH) and
      hexachlorobenzene (HCB) were suggested to contribute to the observed serological
      alterations in eel.

PMID- 15963373
TI  - Structural and functional diversity of microbial communities from a lake sediment
      contaminated with trenbolone, an endocrine-disrupting chemical.
AB  - Effects of trenbolone (TBOH), a hormone used in cattle production, on the
      structure and function of microbial communities in a fresh water sediment from a
      lake in Southern Germany were studied in a microcosm experiment. The microbial
      community structure and the total gene pool of the sediment, assessed by 16S
      rRNA/rDNA and RAPD fingerprint analysis, respectively, were not significantly
      affected by TBOH. In contrast, the N-acetyl-glucosaminidase activity was almost
      50% lower in TBOH treated samples (P<0.05). Also, the substrate utilization
      potential, measured using the BIOLOG system, was reduced after TBOH treatment.
      Interestingly, this potential did not recover at the end of the experiment, i.e.
      19 days after the addition of the chemical. Repeated application of TBOH did not
      lead to an additional reduction in the substrate utilization potential. Overall
      results indicate that microbial community function was more sensitive to TBOH
      treatment than the community structure and the total gene pool.

PMID- 15963374
TI  - Availability of heavy metals for uptake by Salix viminalis on a moderately
      contaminated dredged sediment disposal site.
AB  - Extractability of Cd, Cr, Cu, Ni, Pb, and Zn in a dredged sediment disposal site
      was assessed using single extraction procedures (H2O; 0.01 M CaCl2; 1 M NH4OAc;
      NH4OAc-EDTA; CaCl2-TEA-DTPA). Only Cd and Zn were found to exceed statutory
      threshold values for total content. The field was planted with Salix viminalis
      "Orm" and accumulation of heavy metals in bark, leaves, roots, and wood was
      evaluated at seven sampling locations along an observed gradient in texture and
      pollution. Biomass production was high, ranging from 13.2 to 17.8 t ha(-1) y(-1)
      dry weight. Metal accumulation in aboveground plant parts was low, amounting to
      the following annually extracted mass of metals per ha: 5034 g Zn, 83 g Cd, 145 g
      Cu, 83 g Pb, 12 g Ni and 6 g Cr. The use of accumulating clones and the use of
      soil amendments might enhance extraction efficiency in future research.

PMID- 15963375
TI  - Sources of errors on visuoperceptual tasks: role of education, literacy, and
      search strategy.
AB  - The current study explored possible sources of demographic effects through
      analyses of errors from modified formats of the Benton Visual Retention Test
      (BVRT) completed by African American elders. Results indicate that: (1) reading
      level was a stronger predictor of BVRT performance than years of education; (2)
      on the single-item matching format of the task, individuals with lower reading
      levels disproportionately produced errors on items that differed in geometric,
      rather than spatial features; and (3) on a multiple-choice matching format,
      individuals with lower reading levels committed more errors on items where the
      target was located in the lower half of a 2 x 2 matrix.

PMID- 15963376
TI  - A new method of administering the Grooved Pegboard Test: performance as a
      function of handedness and sex.
AB  - The purpose of the present study was twofold: first to examine the influences of
      sex and handedness on manual performance on the Grooved Pegboard Test; and
      secondly to provide normative data for two versions (Place and Remove tasks) of
      the Grooved Pegboard Test, as previous work (Bryden & Roy, 1999) had suggested
      that the Remove task of the Grooved pegboard may provide a purer measure of motor
      speed of the two hands than the standard administration of the Grooved Pegboard
      Test. One hundred and fifty-three (47 males and 106 females) participants
      completed the Grooved Pegboard Test. Individuals performed the standard version
      of the Grooved Pegboard Test (Place task) and a novel version of the test (Remove
      task). In the standard version, participants were timed on their speed for
      placing the pegs, while in the novel version they were timed on their speed for
      removing the pegs. Results confirmed previously noted hand and sex differences in
      the Place task of the Grooved Pegboard Test, as well as the lack of effect of
      handedness on performance (Bornstein, 1995; Ruff & Parker, 1993). Significant
      performance differences between the hands were also noted for the Remove task.
      Findings also indicated that the Remove task was sensitive to sex and handedness
      effects.

PMID- 15963377
TI  - A simple method to dissociate sensory-attentional and motor-intentional biases in
      unilateral visual neglect.
AB  - A variant of a line bisection test was devised. Patients with unilateral visual
      neglect and control subjects were asked to perform the test, which consisted of
      two subtasks: a verbal and a manual task. The verbal task was newly designed and
      did not require manual responses from the subjects. The manual task was similar
      to conventional line bisection tasks. This paper reports and discusses the
      results obtained from each task and their correlations. This technique is
      compatible with bedside examinations, does not require a complex apparatus, and
      provides useful data for the assessment of unilateral visual neglect.

PMID- 15963378
TI  - "The W and M are mixing me up": use of a visual code in verbal short-term memory
      tasks.
AB  - When normal participants are presented with written verbal short-term memory
      tasks (e.g., remembering a set of letters for immediate spoken recall) there is
      evidence to suggest that the information is re-coded into phonological form. This
      paper presents a single case study of MJK whose reading follows the pattern of
      phonological dyslexia. In short-term memory tasks MJK does not phonologically re
      code written materials but, it is argued, uses a visual code. There are three
      main lines of evidence for this, (a) MJK tends to substitute visually similar
      items for one another, (b) her performance is better with visual than auditory
      stimuli, and (c) she is able to remember numbers (e.g., 8) better than written
      words (e.g., eight). Investigation of short-term memory in others with
      phonological dyslexia is warranted.

PMID- 15963379
TI  - Time ordering in frontal lobe patients: a stochastic model approach.
AB  - Frontal lobe patients reproduced a sequence of capital letters or abstract
      shapes. Immediate and delayed reproduction trials allowed the analysis of short-
      and long-term memory for time order by means of suitable Markov chain stochastic
      models. Patients were as proficient as healthy subjects on the immediate
      reproduction trial, thus showing spared encoding and short-term memory. They
      failed, instead, on the delayed trials with capital letters, but not with random
      shapes, suggesting that their long-term memory impairment did not depend on
      primary deficits for ordering, but on inability to benefit from the
      organisational strategies that improve the retention and retrieval in normal
      subjects.

PMID- 15963380
TI  - Dorsal stream deficits suggest hidden dyslexia among deaf poor readers:
      correlated evidence from reduced perceptual speed and elevated coherent motion
      detection thresholds.
AB  - Prelingual deafness and developmental dyslexia have confounding developmental
      effects on reading acquisition. Therefore, standard reading assessment methods
      for diagnosing dyslexia in hearing people are ineffective for use with deaf
      people. Recently, Samar, Parasnis, and Berent (2002) reported visual evoked
      potential evidence that deaf poor readers, compared to deaf good readers, have
      dorsal stream visual system deficits like those previously found for hearing
      dyslexics. Here, we report new psychometric and psychophysical evidence that
      deficits in dorsal stream function, likely involving extrastriate area MT, are
      associated with relatively poor reading comprehension in deaf adults. Poorer
      reading comprehension within a group of 23 prelingually deaf adults was
      associated with lower scores on the Symbol Digit Modality Test, a perceptual
      speed test commonly used to help identify dyslexia in hearing people.
      Furthermore, coherent dot motion detection thresholds, which reflect the
      functional status of area MT, correlated negatively with reading scores in each
      visual quadrant. Elevated motion thresholds for deaf poor readers were not due to
      general cognitive differences in IQ but were specifically correlated with poor
      perceptual speed. With IQ controlled, a highly reliable right visual field
      advantage for coherent motion detection was found. Additional analyses suggested
      that the functional status of dorsal stream motion detection mechanisms in deaf
      people is related to reading comprehension, but the direction and strength of
      lateralization of those mechanisms is independent of reading comprehension. Our
      results generally imply that dyslexia is a hidden contributor to relatively poor
      reading skill within the deaf population and that assessment of dorsal stream
      function may provide a diagnostic biological marker for dyslexia in deaf people.

PMID- 15963381
TI  - Sex differences in a human analogue of the Radial Arm Maze: the "17-Box Maze
      Test".
AB  - This study investigated sex differences in spatial memory using a human analogue
      of the Radial Arm Maze: a revision on the Nine Box Maze originally developed by
      called the 17-Box Maze Test herein. The task encourages allocentric spatial
      processing, dissociates object from spatial memory, and incorporates a within
      participants design to provide measures of location and object, working and
      reference memory. Healthy adult males and females (26 per group) were
      administered the 17-Box Maze Test, as well as mental rotation and a verbal IQ
      test. Females made significantly fewer errors on this task than males. However,
      post hoc analysis revealed that the significant sex difference was specific to
      object, rather than location, memory measures. These were medium to large effect
      sizes. The findings raise the issue of task- and component-specific sexual
      dimorphism in cognitive mapping.

PMID- 15963382
TI  - The effects of focal and global attentional systems on spatial biases.
AB  - The background page on which a stimulus is presented can influence the allocation
      of attention to that stimulus. The purpose of this study was to learn if there
      are hemispheric asymmetries in how background distraction affects attentional
      processing. Asymmetries were investigated by having right eye dominant subjects
      perform line bisections and manipulating the side of background distraction
      (right versus left), the eye of regard (right versus left), and the type of
      attention allocated (focal versus global). Overall subjects bisected lines to the
      left of center (pseudoneglect) and when viewing with the right eye (versus left)
      deviated more to the left. Subjects had more background distraction when viewing
      symbol than solid lines. Although overall, bias did not differ with the side of
      background distraction or the line being on one side or the other, when subjects
      viewed symbol, but not solid lines, this leftward bias was increased when the
      line was displaced to the right, thereby increasing the size of the left sided
      background. These findings suggest that when engaging the left hemisphere by
      using focused attention and placing the line on the right side, there is more
      distraction than when the right hemisphere is engaged.

PMID- 15963383
TI  - Hemispheric specialization and recognition memory for abstract and realistic
      pictures: a comparison of painters and laymen.
AB  - Recognition memory and hemispheric specialization were assessed for abstract
      colour/black and white pictures of sport situations in painters and visually
      naive subjects using a forced choice yes/no tachistoscopic procedure. Reaction
      times showed a significant three-way interaction of picture type, expertise, and
      visual field, indicating that painters processed the abstract pictures in the
      right hemisphere and sport pictures leftwards relative to the novices. The
      novices showed an overall LVF/RH advantage, strongest for sport pictures. The
      opposing gradients in the painters indicate a preferential change of processing
      strategy by which descriptive systems appear to have developed for figurative,
      but not abstract pictures.

PMID- 15963384
TI  - Perceptual asymmetries are preserved in memory for highly familiar faces of self
      and friend.
AB  - We investigated the effect of familiarity on people's perception of facial
      likeness by asking participants to choose which of two mirror-symmetric chimeric
      images (made from the left or right half of a photograph of a face) looked more
      like an original image. In separate trials the participants made this judgment
      for their own face and for the face of a close friend; half of them matched to a
      true image of the original and half matched to a mirror image of the original. In
      the case of matching to a friend's face presented in the familiar orientation,
      over 80% of participants chose the left-left composite to be a better likeness to
      the original, whereas only 62% showed the same left-side bias when matching to a
      mirror image. The difference is significant, and the result contrasts markedly
      with a second experiment where participants who were unfamiliar with the faces
      showed comparable left-side biases when matching to true or mirror reversed
      images. The result suggests that perceptual asymmetries are retained in our long
      term memory for highly familiar faces. While matching to images of self also
      showed an effect of familiarity, the data in this condition show less evidence of
      perceptual asymmetry and are discussed in relation to recent research on the
      representation of one's own face.

PMID- 15963386
TI  - Quality of care reigns supreme: cardiologists at the helm.

PMID- 15963385
TI  - Monitoring of hematological, inflammatory and oxidative reactions to acute oral
      iron exposure in human volunteers: preliminary screening for selection of
      potentially-responsive biomarkers.
AB  - BACKGROUND: Iron is an essential micronutrient but also a major catalyst of
      oxidative and inflammatory reactions. OBJECTIVE: To evaluate the potential
      utility of selected biomarkers in blood or urine to indicate in vivo oxidative or
      inflammatory response to oral iron intake at pharmacological doses. METHODS:
      Three healthy volunteers provided morning, fasting samples of blood and urine on
      up to 13 study days--3 before, 7 during and 3 following a 7-consecutive-day
      period of receiving 120 mg of iron per day as ferrous sulfate in commercially
      available syrup. A series of 23 biomarkers were measured on each collection of
      biological fluids to monitor iron-responsive changes in biomarkers related to
      hematological or iron status, inflammation and in vivo oxidation. RESULTS: Among
      the inflammatory biomarkers measured, white blood cells, serum CRP and urinary
      neopterin showed no response to iron dosing. Only circulating interleukin-4 (IL
      4) and TNF-alpha had abnormal responses with a time association to the oral iron
      intake. Among the oxidative biomarkers, expression of blood superoxide dismutase
      (SOD), hemoxygenase-1, catalase as well as circulating thiobarbituric acid
      reactive substances (TBARS), total oxidative capacity and carbonyl proteins were
      stable in response to iron exposure. Only urinary TBARS, 8-hydroxy-2
      desoxyguanosine and isoprostanes evidenced consistent or suggestive responses to
      ingestion of the iron challenge. Serum hepcidin concentration increased
      dramatically in all three subjects after only the first 120 mg dose of iron, and
      remained elevated even 9 days after cessation of the iron intervention.
      CONCLUSIONS: Most of the candidate biomarkers show very limited promise as
      response-indicators to oral iron dosing at the 120 mg dosages or lower, but
      circulating IL-4, TNF-alpha as well as urinary TBARS, 8-hydroxy-2-desoxyguanosine
      and isoprostanes showed potential utility as reliable indicators of oxidative and
      inflammatory response to oral ferrous sulfate.

PMID- 15963387
TI  - Alcohol and the cardiovascular system: research challenges and opportunities.
AB  - Excessive alcohol consumption has long been associated with cardiovascular
      disorders, including cardiomyopathy, hypertension, coronary artery disease, and
      stroke. However, recent evidence suggests that moderate alcohol intake can
      actually provide a measure of cardioprotection, particularly against coronary
      heart disease and ischemia-reperfusion injury. To explore the various dimensions
      of these opposing actions of alcohol, the National Institute on Alcohol Abuse and
      Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of
      the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges
      and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the
      following topics: the epidemiology of alcohol and cardiovascular disease,
      clinical manifestations of alcohol, genetics of alcohol and cardiovascular
      disease, mechanisms underlying the molecular and cellular effects of alcohol, the
      application of new and emerging technology, and translation from discovery to
      therapeutic modalities of treatment. The panel concluded that future studies are
      needed to: 1) determine the role of genes and the environment in assessing
      mechanisms underlying the benefits of alcohol use and cardiovascular disease
      risk; 2) define the biological mechanisms underlying alcohol-induced peripheral
      vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing
      enzymes, genetic susceptibility, and pharmacogenomics in determining
      cardiovascular disease risk and effective treatment; 4) determine common
      mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative
      stress and inflammation; 5) assess the role of insulin resistance, blood
      clotting, protein kinase C isoforms, and signal transduction mechanisms mediating
      alcohol's beneficial effects; and 6) explore the potential of stem cells in
      myocardial regeneration and repair in hearts damaged by alcohol.

PMID- 15963388
TI  - Improvement of cardiovascular risk markers by pioglitazone is independent from
      glycemic control: results from the pioneer study.
AB  - OBJECTIVES: This study was performed to assess whether the anti-inflammatory and
      antiatherogenic effects of pioglitazone suggested by animal experiments are
      reproducible in man and independent from improvements in metabolic control.
      BACKGROUND: Type 2 diabetes is associated with increased cardiovascular risk.
      METHODS: A total of 192 patients were enrolled into a six-month, prospective,
      open-label, controlled clinical study. They were randomized to receive either
      pioglitazone (45 mg) or glimepiride (1 to 6 mg, with the intent to optimize
      therapy). Biochemical and clinical markers to assess therapeutic effects included
      HbA1c, fasting glucose, insulin, adiponectin, lipids, high-sensitivity C-reactive
      protein (hsCRP), intracellular adhesion molecule, vascular cell adhesion
      molecule, vascular endothelial growth factor, fibrinogen, von Willebrand factor,
      matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1,
      soluble CD40 ligand, and carotid intima-media thickness (IMT). RESULTS: The study
      was completed by 173 patients (66 female, 107 male; age [+/- SD]: 63 +/- 8 years;
      disease duration: 7.2 +/- 7.2 years; HbA1c: 7.5 +/- 0.9%; pioglitazone arm: 89
      patients). A comparable reduction in HbA1c was seen in both groups (p < 0.001).
      In the pioglitazone group, reductions were observed for glucose (p < 0.001 vs.
      glimepiride group at end point), insulin (p < 0.001), low-density
      lipoprotein/high-density lipoprotein ratio (p < 0.001), hsCRP (p < 0.05), MMP-9
      (p < 0.05), MCP-1 (p < 0.05), and carotid IMT (p < 0.001), and an increase was
      seen in high-density lipoprotein (p < 0.001) and adiponectin (p < 0.001).
      Spearman ranks analysis revealed only one correlation between the reduction in
      cardiovascular risk parameters and the improvement in the metabolic parameters
      (MMP-9 and fasting blood glucose, p < 0.05) CONCLUSIONS: This prospective study
      gives evidence of an anti-inflammatory and antiatherogenic effect of pioglitazone
      versus glimepiride. This effect is independent from blood glucose control and may
      be attributed to peroxisome proliferator-activated receptor gamma activation.

PMID- 15963389
TI  - Use of bivalirudin during percutaneous coronary intervention in patients with
      diabetes mellitus: an analysis from the randomized evaluation in percutaneous
      coronary intervention linking angiomax to reduced clinical events (REPLACE)-2
      trial.
AB  - OBJECTIVES: The objective of this study was to confirm that the efficacy and
      safety of percutaneous coronary intervention (PCI) in diabetic patients are not
      compromised by a bivalirudin-based antithrombotic strategy. BACKGROUND: Previous
      studies have shown a survival benefit with use of platelet glycoprotein (GP)
      IIb/IIIa inhibitors in diabetic patients undergoing PCI. The Randomized
      Evaluation in Percutaneous Coronary Intervention Linking Angiomax to Reduced
      Clinical Events (REPLACE)-2 trial showed the non-inferiority of a strategy of
      bivalirudin with provisional GP IIb/IIIa inhibition compared with routine GP
      IIb/IIIa inhibition. The relative efficacy of these two strategies in diabetic
      patients has not been studied. METHODS: We evaluated the diabetic patients
      enrolled in the REPLACE-2 trial to assess the impact of these antithrombotic
      strategies on the short- and long-term outcome after PCI. RESULTS: The REPLACE-2
      trial enrolled 1,624 diabetic patients and 4,368 non-diabetic patients. Compared
      with non-diabetic patients, diabetic patients had similar short-term outcome but
      higher mortality at 1 year (3.06% vs. 1.85%, p = 0.004). There was no difference
      in short-term or long-term ischemic events among the diabetic patients randomized
      to the two arms. Specifically, the 1-year mortality rate was non-significantly
      lower in the bivalirudin arm, suggesting no differential survival impact of the
      two strategies (2.3% vs. 3.9%). There was less minor bleeding in the bivalirudin
      arm in diabetic patients (12.6% vs. 24.4%, p < 0.001), whereas no difference was
      seen in the incidence of major bleeding (3.0% vs. 3.3%, p = 0.69). CONCLUSIONS:
      Compared with routine GP IIb/IIIa inhibition, the use of bivalirudin with
      provisional GP IIb/IIIa inhibitors in diabetic patients is associated with no
      differences in clinical outcomes at 30 days, a trend toward lesser mortality at 1
      year, and a reduction in minor bleeding.

PMID- 15963390
TI  - Enhanced T-helper-1 lymphocyte activation patterns in acute coronary syndromes.
AB  - OBJECTIVES: We sought to determine whether different stages of coronary artery
      disease (CAD) are associated with distinct differentiation patterns of activated
      T cells. BACKGROUND: Atherosclerosis is an inflammatory disease. However, little
      is known about specific inflammatory cell activation in atherosclerosis, for
      example, the T-helper (Th)1/Th2-balance. METHODS: We studied 18 patients with
      stable angina (SA), 28 patients with acute coronary syndrome (ACS) (16 with
      unstable angina pectoris and 12 with ST-segment elevation myocardial infarction),
      19 patients with unheralded myocardial infarction (UH), and 16 control patients.
      Cytokine patterns and transcription factor signaling pathways of circulating T
      cells were characterized using reverse transcription polymerase chain reaction
      and flow cytometry. RESULTS: Although interferon (IFN)-gamma(+)/CD3(+) T cells
      were approximately 2-fold greater in patients with SA or UH than in control
      subjects, there was a massive expansion of Th1 cells in patients with ACS (p <
      0.001). This increase was paralleled by significantly increased mRNA transcript
      levels for signal-transducer-and-activator-4 (ACS 1.17 +/- 0.14 relative units
      [RU]; control patients 0.44 +/- 0.09 RU; SA 0.67 +/- 0.12 RU; UH 0.61 +/- 0.17
      RU), interleukin-2 (ACS 1.55 +/- 0.51 RU; control patients 0.21 +/- 0.09 RU; SA
      0.54 +/- 0.18 RU; UH 0.45 +/- 0.16 RU), and IFN-gamma in ACS (1.27 +/- 0.39 RU;
      control patients 0.35 +/- 0.09 RU; SA 0.58 +/- 0.11 RU; UH 0.53 +/- 0.24 RU; p <
      0.002). Th2 and Th0 cells were not different across patient subsets. The burden
      of CAD was identical between SA (1.4 +/- 0.2 diseased vessels, 68 +/- 13%
      diameter stenosis) and ACS (1.4 +/- 0.2 diseased vessels, 64 +/- 17% diameter
      stenosis) but significantly greater in patients with UH (2.5 +/- 0.5 diseased
      vessels, 95 +/- 7% diameter stenosis; p < 0.05). CONCLUSIONS: Patients with UH
      have a greater burden of obstructive CAD than SA but no greater T-cell
      activation. Patients with ACS have the same extent of CAD than SA but
      significantly greater activation of Th1 cells that may contribute to the
      increasing instability. Differences in circulating Th1 cells might indicate
      different pathogenic components, leading to ACS and UH.

PMID- 15963391
TI  - Volumetric quantitative analysis of tissue characteristics of coronary plaques
      after statin therapy using three-dimensional integrated backscatter intravascular
      ultrasound.
AB  - OBJECTIVES: The purpose of the present study was twofold: 1) to evaluate the
      usefulness of three-dimensional (3D) integrated backscatter (IB) intravascular
      ultrasound (IVUS) for quantitative tissue characterization of coronary plaques;
      and 2) to use this imaging technique to determine if six months of statin therapy
      alters the tissue characteristics of coronary plaques. BACKGROUND: Three
      dimensional IVUS techniques for quantitative tissue characterization of plaque
      composition have not been developed. METHODS: Radiofrequency (RF) signals were
      obtained using an IVUS system with a 40-MHz catheter. The IB values of the RF
      signal were calculated and color-coded. The 3D reconstruction of the color-coded
      map was performed by computer software. A total of 18 IB IVUS images were
      captured at an interval of 1 mm in each plaque. A total of 52 patients with
      hyperlipidemia were randomized to treatment with pravastatin (20 mg/day, n = 17),
      atorvastatin (20 mg/day, n = 18), or diet (n = 17) for six months. The tissue
      characteristics of arterial plaque in each patient (one arterial segment per
      patient) were analyzed with 3D IB IVUS before and after treatment. RESULTS:
      Significant increases of fibrous volume (pravastatin: 25.4 +/- 6.5% to 28.1 +/-
      6.1%; atorvastatin: 26.2 +/- 5.7% to 30.1 +/- 5.5%) and mixed lesion volume
      (atorvastatin: 25.5 +/- 6.6% to 28.7 +/- 5.1%) and a reduction of lipid volume
      (pravastatin: 25.5 +/- 5.7% to 21.9 +/- 5.3%; atorvastatin: 26.5 +/- 5.2% to 19.9
      +/- 5.5%) were observed after statin therapy. CONCLUSIONS: Statin therapy reduced
      the lipid component in patients with stable angina without reducing the degree of
      stenosis. Three-dimensional IB IVUS offers the potential for quantitative
      volumetric tissue characterization of coronary atherosclerosis.

PMID- 15963392
TI  - Detection of lipid-laden atherosclerotic plaque by wavelet analysis of
      radiofrequency intravascular ultrasound signals: in vitro validation and
      preliminary in vivo application.
AB  - OBJECTIVES: This study examined the feasibility of using a wavelet analysis of
      radiofrequency (RF) intravascular ultrasound (IVUS) signals in detecting lipid
      laden plaque. BACKGROUND: Wavelet analysis is a new mathematical model for
      assessing local changes in a geometrical profile of time-series signals. METHODS:
      Radiofrequency IVUS signals of 85 arbitrarily selected vectors were acquired from
      27 formalin-fixed noncalcified atherosclerotic plaques from human necropsy with a
      digitizer at 500 MHz with 8-bit resolution by use of a 40-MHz IVUS catheter.
      Wavelet analysis of these RF signals was performed using a Daubechies-2 wavelet
      to obtain a color-coded map of the correlation coefficient with the wavelet
      reconstructed over the x-y plane of the wavelet scale and the distance from the
      IVUS catheter. The plaque segment was then examined histologically after being
      stained with Masson's trichrome stain. This technique also was applied in vivo in
      29 human coronary plaque segments. These segments were excised subsequently by
      directional coronary atherectomy and processed for histologic analysis. RESULTS:
      In the in vitro study, histologic examination revealed lipid-laden segments in 29
      vectors. When performing a wavelet analysis with the Daubechies-2 wavelet, the
      color-coded mapping revealed a different pattern in lipid-laden plaques compared
      with other types of plaque. Using this wavelet analysis, lipid-laden plaque could
      be detected with a sensitivity of 83% (24 of 29) and a specificity of 82% (46 of
      56). In the in vivo study, fatty plaque could be detected with a sensitivity of
      81% (13 of 16) and a specificity of 85% (11 of 13) with this method. CONCLUSIONS:
      Wavelet analysis of RF IVUS signals enabled in vitro as well as in vivo detection
      of lipid-laden plaque. This method may be useful in assessing plaque
      vulnerability in patients with coronary artery disease.

PMID- 15963393
TI  - Diagnosis of thin-cap fibroatheromas by a self-contained intravascular magnetic
      resonance imaging probe in ex vivo human aortas and in situ coronary arteries.
AB  - OBJECTIVES: We sought to correlate findings obtained from a self-contained
      magnetic resonance imaging (MRI) probe with plaque morphology of ex vivo human
      aortas and coronary arteries. BACKGROUND: Early detection of thin-cap
      fibroatheromas (TCFAs) may allow for early preventive treatment of acute coronary
      syndromes. We developed an intravascular MRI catheter capable of imaging the
      arterial wall without external magnets or coils by differentiating lipid-rich and
      fibrotic-rich areas of the atherosclerotic plaque on the basis of differential
      water diffusion. METHODS: Aortic samples (n = 16) and coronary arteries were
      obtained within 12 h of death. Coronary specimens were intermediate in
      angiographic severity (30% to 60% luminal narrowing, n = 18). Blinded histologic
      and immunohistochemical analyses of the tissues were performed and correlated to
      MRI findings. RESULTS: The 16 aortic lesions included four ulcerated plaques, two
      TCFAs, two thick-cap fibrous atheromas, two intimal xanthomas, and six adaptive
      intimal thickenings. The MRI scan correctly correlated with the histologic
      diagnosis in 15 (94%) of 16 lesions. The 18 coronary lesions included one plaque
      rupture, three TFCAs, seven thick-cap fibrous atheromas, four fibrocalcific
      plaques, two intimal xanthomas, and one adaptive intimal thickening. The MRI scan
      correlated with the histologic diagnosis in 16 of 18 lesions (sensitivity 100%,
      specificity 89%). CONCLUSIONS: The self-contained intravascular MRI catheter
      successfully identified TCFA and may prove to be an important diagnostic approach
      to determining the presence of lesions with increased risk of causing death or
      myocardial infarction.

PMID- 15963394
TI  - Picking plaques that pop ...

PMID- 15963395
TI  - Incidence and clinical correlates of ruptured plaques in saphenous vein grafts:
      an intravascular ultrasound study.
AB  - OBJECTIVES: The goal of this study was to assess the incidence, clinical
      correlates, and angiographic appearance of ruptured atherosclerotic plaques
      detected in saphenous vein grafts (SVGs). BACKGROUND: Ruptured atherosclerotic
      plaques in native coronary arteries but not in SVGs have been well described with
      intravascular ultrasound (IVUS). METHODS: We reviewed 791 pre-intervention IVUS
      SVG studies and identified 95 ruptured plaques in 76 SVGs in 73 patients.
      Standard clinical, angiographic, and IVUS measurements were collected and/or
      measured. Ruptured plaques were compared with nonruptured plaques in 276 randomly
      selected patients. RESULTS: The IVUS-detected ruptured plaques had
      angiographically complex morphology (95%) with ulceration (79%), intimal flap
      (71%), and sometimes aneurysm formation (14%). Compared with control SVG lesions,
      ruptured plaques occurred more often in patients with acute coronary syndromes,
      in older SVGs (12.3 +/- 5.0 years vs. 8.6 +/- 5.2 years, p < 0.001), and in
      patients with hypercholesterolemia (92% vs. 81%, p = 0.021) and hypertension (78%
      vs. 63%, p = 0.015). Multiple ruptured plaques were identified in 22 patients in
      19 grafts, more often in diabetic patients (55% vs. 29%, p = 0.054). A tear in
      the fibrous cap could be identified in 59% of plaques; in 70% it occurred at the
      shoulder of the plaque and in 30% at the center of the plaque. The IVUS features
      of ruptured plaques included positive remodeling in 71%, which was more common
      than in control plaques (40%, p < 0.001). CONCLUSIONS: Ruptured atherosclerotic
      plaques occur in old SVGs with an incidence of 9.7%. These lesions have a complex
      angiographic appearance and positive remodeling characteristics. This is similar
      to ruptured plaques in native arteries.

PMID- 15963396
TI  - Relationship between carotid artery intima-media thickness and brachial artery
      flow-mediated dilation in middle-aged healthy men.
AB  - OBJECTIVES: We aimed to determine the relationship between carotid intima-media
      thickness (IMT) and brachial artery flow-mediated dilation (FMD) in healthy
      middle-age men. BACKGROUND: Carotid IMT and brachial artery FMD are frequently
      used as surrogate measures of subclinical atherosclerosis. Whereas carotid IMT
      identifies early structural abnormalities, brachial artery FMD, considered a
      bioassay of endothelial function, measures functional vascular integrity. The
      relationship between carotid IMT and brachial artery FMD has not been well
      studied. METHODS: We measured traditional risk factors, carotid IMT, and brachial
      artery FMD in 1,578 middle-aged men without known cardiovascular disease and
      analyzed the relationship between carotid IMT and brachial FMD. RESULTS: Carotid
      IMT correlated with age, systolic blood pressure, body mass index, fasting
      glucose, total and low-density lipoprotein (LDL) cholesterol, and with the
      overall Framingham risk score (p < 0.001 for all), whereas impaired brachial
      artery FMD correlated with systolic and diastolic blood pressure (p < 0.01). No
      relationship was observed between carotid IMT and brachial artery FMD for the
      entire cohort (r = -0.006, p = 0.82) and in subgroups defined by traditional risk
      factors or by quintiles of carotid IMT and brachial FMD. CONCLUSIONS: In middle
      aged healthy men, there is no significant correlation between carotid IMT and
      brachial artery FMD. This finding suggests that these are unique, independent
      surrogates that measure different aspects and stages of early atherosclerosis.
      Further studies are needed to define their role in clinical research and in
      cardiovascular risk assessment.

PMID- 15963397
TI  - Is the association between flow-mediated dilation and cardiovascular risk limited
      to low-risk populations?
AB  - OBJECTIVES: The aim of this research was to study whether the relation between
      endothelial function measured by flow-mediated dilation (FMD) of the brachial
      artery and cardiovascular risk factors is affected by the baseline cardiovascular
      risk. BACKGROUND: Flow-mediated dilation of the brachial artery is widely used as
      a measure of endothelial function. Relations between FMD and most cardiovascular
      risk factors have been described. METHODS: We performed a meta-regression
      analysis of 211 selected articles (399 populations) reporting on FMD and
      cardiovascular risk factors. Mean values of FMD; age; proportion of men;
      proportion of smokers; blood pressure; lipids; glucose; and the presence of
      diabetes mellitus, of hyperlipidemia, and of hypertension were retrieved from the
      articles. The 10-year risk of coronary heart disease (CHD) for each population
      was estimated based on the Framingham risk score. The relation between FMD and
      cardiovascular risk factors was assessed within each risk category by linear
      regression analysis, adjusting for age and gender, and weighted for the study
      size. RESULTS: A relation between FMD and cardiovascular risk factors was most
      clear in the category with lowest baseline risk (below 2.8% per decade). In
      populations with low baseline risk, for each % increase in Framingham risk, FMD
      decreased by 1.42% (95% confidence interval: 0.65 to 2.19). In medium- and high
      risk populations, FMD was not related to risk (-0.02% [-0.27 to 0.22] and 0.06% [
      0.02 to 0.13], respectively). These findings were independent of differences in
      brachial lumen diameter and technical aspects of the FMD measurement.
      CONCLUSIONS: Only in populations at low risk, endothelial function measured by
      FMD is related to the principal cardiovascular risk factors, and to the estimated
      10-year risk of CHD.

PMID- 15963398
TI  - Primary and a half prevention: can we identify asymptomatic subjects with high
      vascular risk?

PMID- 15963399
TI  - Changes in brain natriuretic peptide levels and bioelectrical impedance
      measurements after treatment with high-dose furosemide and hypertonic saline
      solution versus high-dose furosemide alone in refractory congestive heart
      failure: a double-blind study.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of a new treatment
      for refractory congestive heart failure (CHF) on brain natriuretic peptide (BNP)
      plasma levels and hydration station. BACKGROUND: The study was aimed at
      evaluating the effects of the combination of high-dose furosemide and small
      volume hypertonic saline solution (HSS) in refractory CHF patients. METHODS: A
      total of 94 patients (34 women/60 men) with refractory CHF (age 55 to 80 years)
      were enrolled. They had to have an ejection fraction <35%, serum creatinine <2
      mg/dl, blood urea nitrogen <60 mg/dl, a reduced urinary volume, and a low
      natriuresis (<500 ml/24 h and <60 mEq/24 h, respectively). Patients were divided
      (double-blind) into two groups: group 1 (18 women/30 men) received an intravenous
      furosemide (500 to 1,000 mg) plus HSS twice a day in 30 min. Group 2 (16 women/30
      men) received an intravenous bolus of furosemide (500 to 1,000 mg/twice a day)
      alone, for four to six days. At entry, body weight, blood pressure, heart rate,
      and laboratory parameters were checked during hospitalization; BNP levels were
      measured on admission, 6 and 30 days after discharge, while on admission and 6
      days after, impedance plethysmography was performed. The HSS group received 120
      mmol of Na intake versus 80 mmol in non-HSS group. Fluid intake of 1,000 was
      given to both groups. RESULTS: The groups were similar for clinical
      characteristics. A significant increase in daily diuresis and natriuresis was
      observed in HSS group, p < 0.05. The BNP values showed significant intragroup and
      intergroup differences, 6 and 30 days after treatment. The patients from the HSS
      group reached a better hydration state than the non-HSS group after six days. In
      addition, the HSS group showed a significant reduction in hospitalization time
      and readmission rate. CONCLUSIONS: Our data show that the HSS group reached dry
      weight more rapidly, a significantly faster reduction in BNP levels, shorter
      hospitalization stay, and lower incidence in readmissions in the 30-day study
      period.

PMID- 15963400
TI  - Torrent or torment from the tubules? Challenge of the cardiorenal connections.

PMID- 15963401
TI  - Inhibition of awake sympathetic nerve activity of heart failure patients with
      obstructive sleep apnea by nocturnal continuous positive airway pressure.
AB  - OBJECTIVES: This study was designed to determine whether reductions in morning
      systolic blood pressure (BP) elicited by treatment of moderate to severe
      obstructive sleep apnea (OSA) in heart failure (HF) patients are associated with
      a reduction in sympathetic vasoconstrictor tone. BACKGROUND: Daytime muscle
      sympathetic nerve activity (MSNA) is elevated in HF patients with coexisting OSA.
      In our recent randomized trial in HF, abolition of OSA by continuous positive
      airway pressure (CPAP) increased left ventricular ejection fraction (LVEF) and
      lowered morning systolic BP. METHODS: Muscle sympathetic nerve activity, BP, and
      heart rate (HR) of medically treated HF patients (EF <45%) and OSA (apnea
      hypopnea index > or =20/h of sleep) were recorded on the morning after overnight
      polysomnography, and again one month after patients were randomly allocated
      nocturnal CPAP treatment or no CPAP (control). RESULTS: In nine control patients,
      there were no significant changes in the severity of OSA, MSNA, systolic BP, or
      HR. In contrast, in the 8 CPAP-treated patients, OSA was attenuated, and there
      were significant reductions in daytime MSNA (from 58 +/- 4 bursts/min to 48 +/- 5
      bursts/min; 84 +/- 4 bursts/100 heart beats to 72 +/- 5 bursts/100 heart beats; p
      < 0.001 and p = 0.003, respectively), systolic BP (from 135 +/- 5 mm Hg to 120 +/
      6 mm Hg, p = 0.03), and HR (from 69 +/- 2 min(-1) to 66 +/- 2 min(-1); p =
      0.013). CONCLUSIONS: Treatment of coexisting OSA by CPAP in HF patients lowers
      daytime MSNA, systolic BP, and HR. Inhibition of increased central sympathetic
      vasoconstrictor outflow is one mechanism by which nocturnal CPAP reduces awake BP
      in HF patients with moderate to severe OSA.

PMID- 15963402
TI  - Treating sleep apnea in heart failure patients: promises but still no prizes.

PMID- 15963403
TI  - Fish intake and risk of incident heart failure.
AB  - OBJECTIVES: Our aim was to investigate the relation between fish consumption and
      incidence of congestive heart failure (CHF). BACKGROUND: The incidence and health
      burden of CHF are rising, particularly in older persons. Although n-3 fatty acids
      have effects that could favorably influence risk of CHF, the relation between
      fish intake and CHF incidence is unknown. METHODS: Among 4,738 adults age > or
      =65 years and free of CHF at baseline in 1989-90, usual dietary intake was
      assessed using a food frequency questionnaire. In a participant subsample,
      consumption of tuna or other broiled or baked fish, but not fried fish,
      correlated with plasma phospholipid n-3 fatty acids. Incidence of CHF was
      prospectively adjudicated. RESULTS: During 12 years' follow-up, 955 participants
      developed CHF. In multivariate-adjusted analyses, tuna/other fish consumption was
      inversely associated with incident CHF, with 20% lower risk with intake 1 to 2
      times/week (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = 0.64 to
      0.99), 31% lower risk with intake 3 to 4 times/week (HR = 0.69, 95% CI = 0.52 to
      0.91), and 32% lower risk with intake > or =5 times/week (HR = 0.68, 95% CI =
      0.45 to 1.03), compared with intake <1 time/month (p trend = 0.009). In similar
      analyses, fried fish consumption was positively associated with incident CHF (p
      trend = 0.01). Dietary long-chain n-3 fatty acid intake was also inversely
      associated with CHF (p trend = 0.009), with 37% lower risk in the highest
      quintile of intake (HR = 0.73, 95% CI = 0.57 to 0.94) compared with the lowest.
      CONCLUSIONS: Among older adults, consumption of tuna or other broiled or baked
      fish, but not fried fish, is associated with lower incidence of CHF. Confirmation
      in additional studies and evaluation of potential mechanisms is warranted.

PMID- 15963404
TI  - The growing mismatch between patient longevity and the service life of
      implantable cardioverter-defibrillators.
AB  - Implantable cardioverter-defibrillators (ICDs) are lifesaving devices. Over
      100,000 patients received ICDs in 2004 at a cost of $2 billion for the pulse
      generators alone. Because of expanded indications and coverage by Medicare, the
      number of ICD implantations and replacements is expected to increase dramatically
      during the next decade. The average ICD patient at our institution now lives
      nearly 10 years after the procedure. However, the service life of pulse
      generators has decreased from 4.7 +/- 1 year for single-chamber units to 4.0 +/-
      1 year for dual-chamber devices. This mismatch between patient longevity and the
      service life of ICDs poses a significant clinical and economic burden that must
      be addressed. One near-term solution is for manufacturers to provide devices with
      larger batteries so that most patients can have an ICD pulse generator that lasts
      a lifetime. For the long-term, more robust or renewable energy sources are
      needed.

PMID- 15963405
TI  - Are transthoracic echocardiographic parameters associated with atrial
      fibrillation recurrence or stroke? Results from the Atrial Fibrillation Follow-Up
      Investigation of Rhythm Management (AFFIRM) study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the associations of
      transthoracic echocardiographic parameters with recurrent atrial fibrillation
      (AF) and/or stroke. BACKGROUND: The Atrial Fibrillation Follow-up Investigation
      of Rhythm Management (AFFIRM) study, an evaluation of elderly patients with AF at
      risk for stroke, provided an opportunity to evaluate the implications of
      echocardiographic parameters in patients with AF. METHODS: Transthoracic
      echocardiographic measures of mitral regurgitation (MR), left atrial (LA)
      diameter, and left ventricular (LV) function were evaluated in the AFFIRM rate-
      and rhythm-control patients who had sinus rhythm resume and had these data
      available. Risk for recurrent AF or stroke was evaluated with respect to
      transthoracic echocardiographic measures. RESULTS: Of 2,474 patients studied, 457
      had > or =2(+)/4(+) MR, and 726 had a LA diameter >4.5 cm. The LV ejection
      fraction was abnormal in 543 patients. The cumulative probabilities of at least
      one AF recurrence/stroke were 46%/1% after 1 year and 84%/5% by the end of the
      trial (> 5 years), respectively. Multivariate analysis showed that randomization
      to the rhythm-control arm (hazard ratio [HR] = 0.64; p < 0.0001) and a qualifying
      episode of AF being the first known episode (HR = 0.70; p < 0.0001) were
      associated with decreased risk. Duration of qualifying AF episode >48 h (HR =
      1.55; p < 0.0001) and LA diameter (p = 0.008) were associated with an increased
      risk of recurrent AF. Recurrent AF was more likely with larger LA diameters (HR =
      1.21, 1.16, and 1.32 for mild, moderate, and severe enlargement, respectively).
      No transthoracic echocardiographic measures were associated with risk of stroke.
      CONCLUSIONS: In the AFFIRM study, large transthoracic echocardiographic LA
      diameters were associated with recurrent AF, but no measured echocardiographic
      parameter was associated with stroke.

PMID- 15963406
TI  - Measurement of ventricular torsion by two-dimensional ultrasound speckle tracking
      imaging.
AB  - OBJECTIVES: We sought to examine the accuracy/consistency of a novel ultrasound
      speckle tracking imaging (STI) method for left ventricular torsion (LVtor)
      measurement in comparison with tagged magnetic resonance imaging (MRI) (a time
      domain method similar to STI) and Doppler tissue imaging (DTI) (a velocity-based
      approach). BACKGROUND: Left ventricular torsion from helically oriented myofibers
      is a key parameter of cardiac performance but is difficult to measure. Ultrasound
      STI is potentially suitable for measurement of angular motion because of its
      angle-independence. METHODS: We acquired basal and apical short-axis left
      ventricular (LV) images in 15 patients to estimate LVtor by STI and compare it
      with tagged MRI and DTI. Left ventricular torsion was defined as the net
      difference of LV rotation at the basal and apical planes. For the STI analysis,
      we used high-frame (104 +/- 12 frames/s) second harmonic two-dimensional images.
      RESULTS: Data on 13 of 15 patients were usable for STI analysis, and LVtor
      profile estimated by STI strongly correlated with those by tagged MRI (y = 0.95x
      + 0.19, r = 0.93, p < 0.0001, analyzed by repeated-measures regression models).
      The STI torsional velocity profile also correlated well with that by the DTI
      method (y = 0.79x + 2.4, r = 0.76, p < 0.0001, by repeated-measures regression
      models) with acceptable bias. CONCLUSIONS: The STI estimation of LVtor is
      concordant with those analyzed by tagged MRI (data derived from tissue
      displacement) and also showed good agreement with those by DTI (data derived from
      tissue velocity). Ultrasound STI is a promising new method to assess LV torsional
      deformation and may make the assessment more available in clinical and research
      cardiology.

PMID- 15963407
TI  - Assessment of myocardial viability in reperfused acute myocardial infarction
      using 16-slice computed tomography in comparison to magnetic resonance imaging.
AB  - OBJECTIVES: The aim of this study was to examine if contrast-enhanced multislice
      spiral computed tomography (MSCT) is comparable to contrast-enhanced magnetic
      resonance imaging (MRI) for depiction of acute myocardial infarction (MI).
      BACKGROUND: Delayed-enhancement MRI of MI is well established, but there are no
      clinical reports about MSCT for this indication. Early perfusion deficit on MSCT
      has been reported to correlate with the presence of MI. METHODS: A total of 28
      consecutive patients (23 men; 55.9 +/- 11.4 years) with reperfused MI underwent
      contrast-enhanced cardiac 16-slice MSCT. Images were acquired in the arterial
      phase and the late phase 15 min after administration of 120 ml contrast material.
      Within 5 days, patients underwent MRI after administration of 0.2 mmol Gd
      dimeglumine/kg/bodyweight. All examinations were completed within two weeks after
      MI. The area of MI was compared between the different imaging techniques using
      Bland-Altman method and multivariate analysis. Agreement of the contrast
      enhancement patterns was evaluated with a weighted kappa test. RESULTS: Mean
      infarct size on MRI was 31.2 +/- 22.5% per slice compared with 33.3 +/- 23.8% per
      slice for late-enhancement MSCT and 24.5 +/- 18.3% per slice for early-perfusion
      deficit MSCT. Bland-Altman data showed a good agreement between late-enhancement
      MRI and late-enhancement MSCT. Contrast enhancement patterns demonstrated an
      excellent agreement between late-enhancement MRI and late-enhancement MSCT (kappa
      = 0.878). The results were worse comparing MRI and early-phase MSCT (kappa =
      0.635). CONCLUSIONS: Multislice spiral computed tomography allows for the
      assessment of acute MI. Late-enhancement MSCT appears to be as reliable as
      delayed contrast-enhanced MRI in assessing infarct size and myocardial viability
      in acute MI.

PMID- 15963408
TI  - Planimetry of mitral valve stenosis by magnetic resonance imaging.
AB  - OBJECTIVES: We sought to determine whether noninvasive planimetry of the mitral
      valve area (MVA) by magnetic resonance imaging (MRI) is feasible and reliable in
      patients with mitral stenosis (MS). BACKGROUND: Accurate assessment of MVA is
      particularly important for the management of patients with valvular stenosis.
      Current standard techniques for assessing the severity of MS include
      echocardiography (ECHO) and cardiac catheterization (CATH). METHODS: In 22
      patients with suspected or known MS, planimetry of MVA was performed with a 1.5-T
      magnetic resonance scanner using a breath-hold balanced gradient echo sequence
      (true FISP). Data were compared with echocardiographically determined MVA (ECHO
      MVA, n = 22), as well as with invasively calculated MVA by the Gorlin-formula at
      (CATH-MVA, n = 17). RESULTS: The correlation between MRI- and CATH-MVA was 0.89
      (p < 0.0001), and the correlation between MRI- and ECHO-MVA was 0.81 (p <
      0.0001). The MRI-MVA slightly overestimated CATH-MVA by 5.0% (1.60 +/- 0.45 cm(2)
      vs. 1.52 +/- 0.49 cm(2), p = NS) and ECHO-MVA by 8.1% (1.61 +/- 0.42 cm(2) vs.
      1.48 +/- 0.42 cm(2), p < 0.05). On receiver-operating characteristic curve
      analysis, a value of MRI-MVA below 1.65 cm(2) indicated mitral stenosis (CATH-MVA
      < or =1.5 cm(2)), with a good sensitivity and specificity (89% and 75%,
      respectively). CONCLUSIONS: Magnetic resonance planimetry of the mitral valve
      orifice in mitral stenosis offers a reliable and safe method for noninvasive
      quantification of mitral stenosis. In the clinical management of patients with
      mitral stenosis, it has to be considered that planimetry by MRI slightly
      overestimates MVA, as compared with MVA calculated echocardiographically and at
      catheterization.

PMID- 15963409
TI  - Hemodynamic comparison of bioprostheses for complete supra-annular position in
      patients with small aortic annulus.
AB  - OBJECTIVES: The present study evaluates complete supra-annular bioprostheses in
      patients with an aortic annulus of 18 to 23 mm in diameter. BACKGROUND: Aortic
      valve replacement in patients with small aortic annulus using stented
      bioprostheses is often associated with unsatisfactory hemodynamic results and
      high incidence of patient-prosthesis mismatch. METHODS: Between February 2000 and
      January 2004, 156 patients with aortic valve disease and an aortic annulus of 18
      to 23 mm in diameter received the stented bovine Soprano (Sorin Biomedica Cardio,
      Saluggia, Italy) (n = 18), Perimount (Edwards Lifesciences, Irvine, California)
      (n = 52), Perimount Magna (Edwards Lifesciences) (n = 42), or the stented porcine
      Mosaic (Medtronic Inc., Minneapolis, Minnesota) (n = 44) bioprostheses.
      Intraoperatively, the surgeon measured the aortic annulus diameter by inserting a
      hegar dilator. Thus, postoperative hemodynamic results could be referred to the
      patient's aortic annulus diameter instead of referring the results to the labeled
      valve size. This allows for objective comparisons between different valve types.
      RESULTS: There was no significant difference in hemodynamic results between the
      different valve types in patients with an aortic annulus 18 to 20 mm. In patients
      with an annulus 21 to 23 mm, the Magna was significantly superior to the other
      investigated devices in mean pressure gradient, effective orifice area, and
      incidence of patient-prosthesis mismatch. There was no significant difference
      between the complete supra-annular bioprostheses Mosaic and Soprano and the intra
      supra-annular Perimount valve. CONCLUSIONS: In patients with an aortic annulus of
      18 to 20 mm in diameter, hemodynamic performance is independent of the implanted
      stented valve type and the annular position. Root enlargement or stentless valves
      may be beneficial alternatives. Patients with annulus diameter 21 to 23 mm
      benefit from the Magna in complete supra-annular position leading to superior
      hemodynamic results.

PMID- 15963410
TI  - Intracoronary ultrasound assessment late after the arterial switch operation for
      transposition of the great arteries.
AB  - OBJECTIVES: This research was undertaken to assess the status of the coronary
      wall morphology late after the arterial switch operation (ASO) for transposition
      of the great arteries employing intravascular ultrasound (IVUS). BACKGROUND: Long
      term patency of the reimplanted coronary arteries is a key issue after ASO.
      Follow-up studies have demonstrated coronary obstruction in up to 8% of patients
      that may be related to progressive fibrocellular intimal thickening. METHODS:
      Twenty-two asymptomatic children were enrolled at a median age of 9.5 years
      (range 5 to 22 years); IVUS images were obtained in 20 children at cardiac
      catheterization 5.0 to 21.6 years after the operation (in two cases IVUS study
      was not feasible due to technical constraints). Quantitative analysis was
      performed in 37 coronary arteries involving segments with a mean length of 28.4
      +/- 1.8 mm. RESULTS: Thirty-three arteries (89%) displayed variable degrees of
      proximal eccentric intimal proliferation, with the maximal intimal thickening
      being 0.26 +/- 0.14 mm (range 0.06 to 0.71 mm) at the most thickened site.
      According to the Stanford classification, all children had coronary artery
      involvement with 50% having moderate-to-severe lesions (>0.3 mm). No risk factors
      for such abnormalities were encountered, including age, origin of the coronary
      arteries, hemodynamics, and follow-up duration after surgery. CONCLUSIONS:
      Intravascular ultrasound assessment late after the ASO revealed proximal
      eccentric intimal thickening in most of the studied vessels. This observation
      suggests the development of early atherosclerosis in the reimplanted coronary
      arteries, which may have a role in the genesis of late coronary events.

PMID- 15963411
TI  - Real-time magnetic resonance-guided endovascular repair of experimental abdominal
      aortic aneurysm in swine.
AB  - OBJECTIVES: This study tested the hypotheses that endografts can be visualized
      and navigated in vivo solely under real-time magnetic resonance imaging (rtMRI)
      guidance to repair experimental abdominal aortic aneurysms (AAA) in swine, and
      that MRI can provide immediate assessment of endograft apposition and aneurysm
      exclusion. BACKGROUND: Endovascular repair for AAA is limited by endoleak caused
      by inflow or outflow malapposition. The ability of rtMRI to image soft tissue and
      flow may improve on X-ray guidance of this procedure. METHODS: Infrarenal AAA was
      created in swine by balloon overstretch. We used one passive commercial
      endograft, imaged based on metal-induced MRI artifacts, and several types of
      homemade active endografts, incorporating MRI receiver coils (antennae). Custom
      interactive rtMRI features included color coding the catheter-antenna signals
      individually, simultaneous multislice imaging, and real-time three-dimensional
      rendering. RESULTS: Eleven repairs were performed solely using rtMRI,
      simultaneously depicting the device and soft-tissue pathology during endograft
      deployment. Active devices proved most useful. Intraprocedural MRI provided
      anatomic confirmation of stent strut apposition and functional corroboration of
      aneurysm exclusion and restoration of laminar flow in successful cases. In two
      cases, there was clear evidence of contrast accumulation in the aneurysm sac,
      denoting endoleak. CONCLUSIONS: Endovascular AAA repair is feasible under rtMRI
      guidance. Active endografts facilitate device visualization and complement the
      soft tissue contrast afforded by MRI for precise positioning and deployment.
      Magnetic resonance imaging also permits immediate post-procedural anatomic and
      functional evaluation of successful aneurysm exclusion.

PMID- 15963412
TI  - Different effects of a high-cholesterol diet on ischemic cardiac dysfunction and
      remodeling induced by coronary stenosis and coronary occlusion.
AB  - OBJECTIVES: The aim of the study was to assess whether and how the high
      cholesterol diet (HCD)-related worsening of heart failure differs between
      coronary stenosis (CS)-induced myocardial ischemia and coronary occlusion-induced
      myocardial infarction (MI). BACKGROUND: An HCD, a risk factor for coronary artery
      disease, also worsens ischemic heart failure. Although accelerated coronary
      plaque formation may be a cause of this, other mechanism(s), such as its effects
      through the coronary microcirculation, remain to be clarified. METHODS: In rats
      fed a normal chow diet or HCD, CS or MI was created surgically, and we assessed
      left ventricular (LV) function by echocardiography and myocardial inflammation by
      histopathology. In the CS groups, CS severity by histopathology, myocardial
      perfusion by microspheres, myocardial protein kinase C (PKC) translocation by
      Western blotting, and myocardial endothelial nitric oxide (NO) function were also
      investigated by the in vitro myocardial oxygen consumption method. RESULTS:
      Coronary stenosis impaired myocardial endothelial NO function and reduced
      coronary flow reserve, evoking myocardial ischemia, as shown by PKC- activation,
      myocardial inflammation, fibrosis, cardiac dysfunction, and remodeling. By
      itself, HCD greatly augmented such CS-induced myocardial abnormalities without
      modulating the CS severity. Such detrimental effects of HCD were ameliorated by
      supplying a cofactor of endothelial NO synthase-tetrahydrobiopterin. In contrast,
      MI-induced heart failure was not aggravated by HCD. CONCLUSIONS: The CS-induced
      ischemic myocardium seems to be more susceptible to the pro-inflammatory effect
      of HCD than infarcted myocardium, leading to aggravation of LV dysfunction and
      remodeling via modification of the coronary circulation downstream of the
      epicardial CS site, partly through impairment of endothelial NO.

PMID- 15963413
TI  - Late angiographic stent thrombosis (LAST) events with drug-eluting stents.
AB  - OBJECTIVES: We sought to describe the incidence of late angiographic stent
      thrombosis (LAST) events in an unselected drug-eluting stent (DES) population.
      BACKGROUND: Concerns have been raised that LAST may be a potential limitation of
      DES. METHODS: We have previously reported the angiographic incidence of early
      stent thrombosis (1.0%) in this prospective cohort of 2,006 patients treated with
      either sirolimus-eluting stents (SES) (n = 1,017) or paclitaxel-eluting stents
      (PES) (n = 989). We continued long-term follow-up to determine the incidence of
      LAST events, defined as angiographically proven stent thrombosis associated with
      acute symptoms more than 30 days after DES implantation. All patients had at
      least 1 year of follow-up, mean duration 1.5 years. RESULTS: There were eight
      angiographically confirmed LAST events in seven patients: three with SES (at 2,
      25, and 26 months) and five with PES (at 6, 7, 8, 11, and 14.5 months). Three
      cases were related to complete cessation of antiplatelet therapy, two cases
      occurred while patients were on aspirin therapy within one month of cessation of
      clopidogrel, and three cases occurred at a time when patients were apparently
      clinically stable on aspirin monotherapy. We observed no cases of LAST in
      patients who were on dual antiplatelet therapy. Two deaths occurred directly as a
      result of LAST. CONCLUSIONS: Angiographically proven late stent thrombosis occurs
      with an incidence of at least 0.35% (95% confidence limits 0.17% to 0.72%) in
      patients treated with DES. Importantly, it may also occur when patients are
      stable on antiplatelet monotherapy.

PMID- 15963414
TI  - The growth of diagnostic imaging services.

PMID- 15963415
TI  - Diastolic dysfunction and Doppler echocardiography.

PMID- 15963417
TI  - Vascular complications and arteriotomy closure devices during percutaneous
      coronary procedures.

PMID- 15963418
TI  - Heart failure training: care for older adults with chronic heart failure.

PMID- 15963422
TI  - Exposure to ethanol induces oxidative damage in the pituitary gland.
AB  - Chronic exposure of pubertal male rats to ethanol results in a decline in serum
      testosterone and decreased or inappropriately normal serum luteinizing hormone
      (LH) and follicle stimulating hormone (FSH) levels suggesting a functional defect
      in the pituitary. The molecular mechanisms behind this disorder are undefined. A
      role for ethanol-induced oxidative damage in the pathophysiology is supported by
      studies in liver, muscle, and heart of experimental animals, but there is limited
      evidence in the pituitary. We examined markers of oxidative damage to lipids and
      proteins in pituitaries from rats consuming ethanol for 5, 10, 20, 30, and 60
      days in addition to markers of damage to nucleic acids in pituitaries after 60
      days of ethanol exposure. There were increases in 8-oxo-deoxyguanosine
      immunoreactivity, a marker of oxidative damage to nucleic acids, and an overall
      increase in malondialdehyde and 4-hydroxynonenal, markers of lipid peroxidation.
      Protein carbonylation and protein nitrotyrosination, markers of protein
      oxidation, were significantly increased after 30 days and 60 days of ethanol
      consumption, respectively. After 60 days of ethanol exposure, TUNEL assay
      revealed that cell death in the ethanol-treated pituitaries was not significantly
      different from that in the pair-fed controls at the time of examination. We also
      measured serum testosterone, FSH, and LH after ethanol consumption for 5, 10, 20,
      30, and 60 days. Through 5 to 60 days of ethanol exposure, testosterone levels
      were consistently lower whereas LH and FSH were inappropriately unchanged,
      suggesting pituitary malfunction. These results provide evidence for ethanol
      induced oxidative damage at the pituitary level, which may contribute to
      pituitary dysfunction.

PMID- 15963423
TI  - Ethanol-induced alterations in Rab proteins: possible implications for pituitary
      dysfunction.
AB  - Chronic exposure of pubertal male rats to ethanol results in a decline in serum
      testosterone, increased gonadotropins, pituitary luteinizing hormone (LH) and
      follicle stimulating hormone (FSH) content, and decreased or inappropriately
      normal serum LH and FSH levels, suggesting impaired secretory release of
      gonadotropins. The molecular mechanisms behind this disorder are undefined, but a
      disruption of vesicle-mediated secretory processes is possible because
      intracellular protein trafficking pathways are involved in secretion of
      glycoproteins such as FSH and LH. Because small GTP-binding proteins of Rab
      family have been implicated as key regulators of membrane and protein trafficking
      in mammalian cells, this study was designed to test if ethanol-impaired pituitary
      FSH and LH secretion is associated with changes in Rab proteins, particularly
      Rab1B, Rab3B, Rab6, and Rab11. Male Sprague-Dawley rats 35 days old were pair-fed
      a Lieber-DeCarli diet with ethanol or without ethanol for 5 to 60 days. After
      ethanol exposure, serum testosterone levels decreased while LH and FSH were
      inappropriately unchanged. Immunohistochemical staining showed decreased Rab1B,
      Rab3B, and Rab11 protein levels in ethanol-treated pituitaries. Immunoblotting
      showed that ethanol induced a transient reduction in Rab6 after 5 days of ethanol
      exposure, whereas Rab3B decreased after 20 days, Rab11 after 30 days, and Rab1B
      after 60 days. Despite these changes in Rab proteins, mRNA levels were unaffected
      by ethanol exposure. We concluded that reductions in key Rab proteins may lead to
      altered vesicle trafficking and may play a role in disruption of pituitary FSH
      and LH secretion caused by ethanol.

PMID- 15963424
TI  - Sex differences in ethanol liquid diet consumption in Sprague-Dawley rats.
AB  - There are reports of sex differences in ethanol intake between different strains
      of male and female rats; however, ethanol consumption (via an ethanol liquid
      diet) and blood ethanol levels (BELs) between male and female rats of the Sprague
      Dawley strain have not been studied. Therefore, the aims of this study were to
      examine body growth, ethanol consumption (ml/day and g.kg(-1).day(-1)), and BELs
      in adult male and female (n=6-8 per group; sham-operated and ovariectomized)
      Sprague-Dawley rats consuming different concentrations (3% to 9% volume/volume)
      of the Lieber-DeCarli liquid ethanol diet. Throughout the study, male rats
      weighed significantly more than both female groups, and ovariectomized female
      rats weighed more than sham female rats. Ethanol diet consumption (ml/day) was
      significantly greater in male rats than in female rats at higher ethanol
      concentrations, whereas, when the diet consumption was expressed in grams of
      ethanol per kilogram of body weight per day, the sham female group was shown to
      consume significantly more ethanol than the male group. Even though there were
      differences in ethanol intake, BELs were similar among the groups. The data
      indicate that, similar to other strains, Sprague-Dawley rats also exhibit sex
      differences in their pattern of body growth (weight gain) and ethanol intake;
      however, BELs were similar among the groups.

PMID- 15963425
TI  - Effects of acute administration of ethanol on cerebral glucose utilization in
      adult alcohol-preferring and alcohol-nonpreferring rats.
AB  - Local cerebral glucose utilization (LCGU) rates, as determined by the [(14)C]-2
      deoxyglucose (2-DG) technique, were examined after acute ethanol administration
      within selected brain regions of alcohol-preferring (P) and alcohol-nonpreferring
      (NP) rats. Adult male P and NP rats were injected with saline, 0.25 g/kg, or 1.0
      g/kg ethanol, intraperitoneally (ip), 10 min before an intravenous bolus of
      [(14)C]2-DG (125 microCi/kg). Timed arterial blood samples were collected over 45
      min and assayed for plasma glucose, ethanol, and [(14)C]2-DG levels. Image
      densities were determined using quantitative autoradiography and LCGU values
      calculated. Data were collected from several key limbic, basal ganglionic,
      cortical, and subcortical structures. Low-dose ethanol (0.25 g/kg) significantly
      decreased LCGU rates in several brain regions including the medial prefrontal
      cortex, olfactory tubercles, and the CA1 subregion of the hippocampus of P rats.
      Low-dose ethanol had no significant effects on LCGU rates in the NP rats.
      Moderate-dose ethanol (1.0 g/kg) also significantly lowered LCGU rates in many
      brain regions of P rats, including key limbic structures, such as the medial
      prefrontal cortex, olfactory tubercles, ventral tegmental area, basolateral
      nucleus of the amygdala, lateral septum, and ventral pallidum. Moderate-dose
      ethanol also significantly lowered LCGU rates in the medial prefrontal cortex as
      well as in the habenula of NP rats. All other regions were unaffected in the NP
      rats. These findings support the suggestion that certain central nervous system
      regions of P rats may be more sensitive than those of NP rats to the effects of
      low to intermediate doses of ethanol.

PMID- 15963426
TI  - Effects of ethanol drinking on central nervous system functional activity of
      alcohol-preferring rats.
AB  - The [(14)C]-2-deoxyglucose (2-DG) technique was used to assess the rates of local
      cerebral glucose utilization (LCGU) in key limbic, cerebral cortical,
      hippocampal, basal ganglionic, and subcortical regions of alcohol-preferring (P)
      rats following chronic 24-h free-choice ethanol drinking. Adult male P rats were
      submitted to (1) 8 continuous weeks of two-bottle access to 15% ethanol and water
      (E-C group); (2) 8 weeks of identical two-bottle access followed by 2 weeks of
      ethanol deprivation (E-D group); (3) cycles of 2 weeks of two-bottle ethanol
      access and 2 weeks of deprivation, repeated for four cycles (E-RD group); or (4)
      water only treatment [ethanol-naive group (E-N group)]. A single pulse of [(14)C]
      2-DG (125 microCi/kg) was administered via a venous catheter, and timed arterial
      blood samples were collected over 45 min and later assayed for plasma glucose and
      [(14)C]-2-DG concentrations. Quantitative autoradiography was used to determine
      [(14)C] densities, and LCGU values were calculated. With the exception of a few
      small differences in the hippocampus, no significant differences were found in
      any of the central nervous system (CNS) regions examined among the four
      experimental groups of P rats. Animals in the E-D group had lower LCGU rates in
      the anterior hippocampal CA1 subregion than animals in the E-N, E-C, and E-RD
      groups. In the anterior hippocampal CA3 subregion and the anterior hippocampal
      dentate gyrus, the E-D group had significantly lower LCGU rates than the E-RD
      group. Overall, the results of this study indicate that 24-h ethanol-drinking
      experience has little effect on CNS functional neuronal activity in P rats.

PMID- 15963427
TI  - Role of dopamine in behavioral sensitization to ethanol in DBA/2J mice.
AB  - Behavioral sensitization has been proposed to play an important role in
      addiction. Elucidation of the neural processes mediating sensitization may
      therefore lead to the development of new pharmacotherapeutic treatments. A large
      number of studies have examined sensitization to psychostimulants and morphine.
      In contrast, despite the prevalence of alcoholism, the neural processes
      underlying sensitization to ethanol have not been identified. The aim of the
      present study was to examine the role of different components of the dopamine
      system in sensitization to the locomotor stimulant effects of ethanol in DBA/2J
      mice. Sensitization was induced by administering ethanol [2 g/kg
      intraperitoneally (ip)] before locomotor activity trials. Control groups received
      saline (12.5 ml/kg ip) before each activity trial. The ability of the dopamine
      uptake inhibitors GBR 12909 (3.33-10.0 mg/kg) and bupropion (20 and 30 mg/kg) to
      cross-sensitize to ethanol was then examined. In addition, the effects of SKF
      82958 (0.1-1.0 mg/kg), a dopamine D(1) (D(1)) receptor agonist, quinpirole (0.05
      and 0.1 mg/kg), a dopamine D(2)/D(3) (D(2)/D(3)) receptor agonist, and a
      combination of SKF 82958 and quinpirole were examined. Cross-sensitization was
      observed between the dopamine uptake inhibitor GBR 12909 and ethanol. In
      contrast, the less selective uptake inhibitor bupropion did not exhibit cross
      sensitization. Similarly, stimulation of D(1) and D(2)/D(3) receptors did not
      cause cross-sensitization even when the agonists were administered together.
      Taken together, these data suggest that sensitization to ethanol is associated
      with changes in the dopaminergic system.

PMID- 15963428
TI  - Fast neutron radiography scanner for the detection of contraband in air cargo
      containers.
AB  - There is a growing need to rapidly scan bulk air cargo for contraband such as
      illicit drugs and explosives. The Commonwealth Science and Industrial Research
      Organisation (CSIRO) have been working with Australian Customs Service to develop
      a scanner capable of directly scanning airfreight containers in 1--2 minutes
      without unpacking. The scanner combines fast neutron and gamma-ray radiography to
      provide high-resolution images that include information on material composition.
      A full-scale prototype scanner has been successfully tested in the laboratory and
      a commercial-scale scanner is due to be installed at Brisbane airport in 2005.

PMID- 15963429
TI  - Development of activity standard for 90 Y microspheres.
AB  - (90)Y microspheres are important therapeutic radiopharmaceuticals used in the
      treatment of liver cancer through a process known as selective internal radiation
      therapy. SIR-spheres is a radiopharmaceutical product that is comprised of (90)Y
      microspheres suspended in sterile, pyrogen-free water for injection into
      patients. It is necessary to establish for the SIR-spheres production the
      capability of accurately measuring the activity of this product to a traceable
      national measurement standard. An activity standard for SIR-spheres was developed
      from a standard for (90)Y solution, employing a highly quantifiable chemical
      digestion process. Calibration factors for the manufacturer's ionisation chambers
      were determined for 1 and 5 ml of the SIR-spheres product placed in Wheaton
      vials, for both 34% and 44% of (90)Y microsphere concentration.

PMID- 15963430
TI  - Combination of chemical separation and data treatment for 55 Fe, 63 Ni, 99 Tc,
      137 Cs and 90 Sr/90Y activity determination in radioactive waste by liquid
      scintillation.
AB  - Routine operations involving nuclear reactors and decommissioning activities
      require numerous chemical analyses. Most of the procedures developed for these
      chemical characterisations involve several separation steps to prepare the sample
      for measurement. Chemical treatments are time- and manpower-consuming, labour
      intensive and produce significant quantities of waste. In order to address this
      problem, we evaluate a data treatment procedure (multivariate calibration--PLS),
      which we propose as a substitute to some of these separation steps. Mixtures of
      beta emitter radionuclides of increasing complexity ((90)Sr/(90)Y--(99)Tc,
      (90)Sr/(90)Y--(99)Tc--(63)Ni--(137)Cs and (90)Sr/(90)Y--(99)Tc--(63)Ni--(137)Cs-
      (55)Fe) have been measured by liquid scintillation (LS) counting. The influences
      of quenching and level of activity was evaluated and the activity of unknown
      samples determined. Despite the spectra overlapping and low resolution of LS,
      relative errors in the activities quantification of unknown samples inside the
      range covered by the calibration matrix are lower than 15% whatever the number of
      radionuclides included in the solution was.

PMID- 15963431
TI  - Evaluation of the depth-ratio and backscattering-factor methods in quality
      control measurements of electron beam energies.
AB  - Sensitivities of two different methods for evaluating electron beam energy have
      been investigated. One of them uses the ratio of ionization at two depths
      corresponding to two different points on the depth curve of ionization. The other
      one uses the magnitude of backscattering by lead as a measure of the electron
      beam energy. The depth-ratio method was found to be sensitive and practical for a
      routine quality control program. The sensitivity of the backscattering effect was
      found to be insufficient for electron energies higher than 12 MeV.

PMID- 15963432
TI  - Fullerene-pyropheophorbide a complexes as sensitizer for photodynamic therapy:
      uptake and photo-induced cytotoxicity on Jurkat cells.
AB  - The main challenge in searching for new photosensitizers is to improve their
      specificity for target cells to avoid toxicity towards normal cells. New modular
      drug delivery systems were proposed consisting of a multiplying unit with the
      property of carrying several drug moieties and an addressing unity with high
      selectivity for target cells. Following this concept, two new fullerene-bis
      pyropheophorbide a derivatives were synthesized: a mono-(FP1) and a hexa-adduct
      (FHP1). The photophysical characterization of the compounds revealed
      significantly different parameters related to the number of addends at the
      fullerene core. In this study, the derivatives were tested with regard to their
      intracellular uptake and photosensitizing activity towards human leukemia T
      lymphocytes (Jurkat cells) in comparison with the free sensitizer,
      pyropheophorbide a. The C(60)-hexa-adduct FHP1 resulted to have a significative
      phototoxic activity (58% dead cell, after a dose of 400 mJ/cm(2), 688 nm) while
      the mono-adduct FP1 had a very low phototoxicity and only at higher light doses.
      The photosensitizing activity of the fullerene hexa-adduct, FHP1, resulted to be
      lower than that of pyropheophorbide a. The lesser intracellular concentration
      reached by the C(60)-hexa-adduct FHP1 is probably the reason for its lower
      phototoxicity with respect to pyropheophorbide a.

PMID- 15963433
TI  - Acrylamide-quenching of Rhizomucor miehei lipase.
AB  - Steady-state and time-resolved fluorescence-quenching measurements have been
      performed to study multitryptophan lipase from filamentous fungus Rhizomucor
      miehei. Using the steady-state acrylamide fluorescence quenching data and the
      fluorescence-quenching-resolved-spectra (FQRS) method, the total emission
      spectrum of native ("closed-lid") lipase has been decomposed into two distinct
      spectral components accessible to acrylamide. According to FQRS analysis, more
      quenchable component has a maximum of fluorescence emission at about 352 nm
      whereas less quenchable component emits at about 332 nm. The redder component
      participates in about 60-64% of the total lipase fluorescence and may be
      characterized by the dynamic and static quenching constants equal to K(1) = 3.75
      M(-1) and V(1) = 1.12 M(-1), respectively. The bluer component is quenchable via
      dynamic mechanism with K(2) = 1.97 M(-1). Significant difference in the values of
      acrylamide bimolecular rate quenching constants estimated for redder and bluer
      component (i.e., k(q) = 1.2 x 10 (9) M(-1)s (-1) vs. k(q) = 4.3 x 10(8) M(-1) s(
      1), respectively), suggests that tryptophan residues in fungal lipase are not
      uniformly exposed to the solvent.

PMID- 15963434
TI  - Encapsulation of porphyrins and chlorins in biodegradable nanoparticles: the
      effect of dye lipophilicity on the extravasation and the photothrombic activity.
      A comparative study.
AB  - In the present work, we performed a preclinical inter-comparison study using
      several photosensitizers with the goal of optimizing photodynamic therapy (PDT)
      for the treatment of choroidal neovascularization (CNV) associated with age
      related macular degeneration. The tested molecules were the porphyrins meso
      tetraphenylporphyrin (TPP) and meso-tetra-(4-carboxyphenyl)-porphyrin (TCPP), and
      the chlorins pheophorbide-a (Pheo-a) and chlorin e(6) (Ce(6)). Each of these
      molecules was entrapped in biodegradable nanoparticles (NP) based on poly(d,l
      lactic acid). The influence of the degree of lipophilicity on the incorporation
      efficiency of the drug in the NPs, and on the dye leakage from blood vessels as
      well as on the photothrombic efficiency was investigated using the chick
      chorioallantoic membrane (CAM) as in vivo model. NP characterization showed that
      the dye was more effectively entrapped in the polymeric matrix when its degree of
      lipophilicity increased. While less lipophilic compounds (TCPP, Ce(6))
      extravasate rather easily, the more lipophilic dyes (TPP, Pheo-a) tend to remain
      inside the blood vessels. After injection of a drug dose of 1 mg/kg body weight
      and a drug-light application interval of 1 min, irradiation with light doses
      ranging from 5 to 20 J/cm(2) led to the highest photothrombic efficiency when
      using the NPs loaded with the most lipophilic molecule (TPP). The latter induced
      vascular damage, which was significantly higher than that observed with the other
      molecules tested. Thus, in addition to minimal leakage from blood vessels, the
      TPP in NP formulation exhibited photothrombic efficiency similar to Visudyne
      which was also tested in the CAM model.

PMID- 15963435
TI  - Photochemistry of the alkaloids eudistomin N (6-bromo-nor-harmane) and eudistomin
      O (8-bromo-nor-harmane) and other bromo-beta-carbolines.
AB  - The UV-absorption, fluorescence excitation and emission spectra of the alkaloids
      eudistomin N (6-bromo-nor-harmane) and eudistomin O (8-bromo-nor-harmane) were
      described. In order to perform a comparative analysis, we also studied other
      bromo-beta-carbolines and the corresponding non-substituted-carboline. Thus, 6
      bromo-, 8-bromo-, 6,8-dibromo-, 3,6-dibromo- and 3,6,8-tribromo-derivatives of
      nor-harmane, harmane and harmine were studied. These studies were performed in
      EtOH and in EtOH + 1% perchloric acid solutions (pa). Furthermore, fluorescence
      quantum yields (phi(f)) in acetonitrile and acetonitrile + 1% perchloric acid
      solutions at 298 K were measured. The HOMO and LUMO energy, the positions
      (lambda(max)) and oscillator strength (f) of the (1)S(1) <--(1)S(0) band for all
      the neutral and protonated beta-carbolines studied was calculated and compared
      with the experimental data. The pK(a) values in aqueous solution for eudistomin N
      and O (6-bromo- and 8-bromo-nor-harmane), for 6-bromo-, 8-bromo- and 6,8-dibromo
      harmane, and for 6-bromo- and 8-bromo-harmine were spectrophotometrically
      measured (pK((a)(H(2)O))) . The change of the acid-base character of these
      compounds on going from the ground state (pK(a)) to the first electronic excited
      singlet state (pK(a)(*)) as DeltapK(a) = pK(a)(*)-pK(a) = 0.625 Deltanu /T, in
      ethanol solution at 298 K were calculated (DeltapK(a(EtOH))). Proton affinities
      (PA) for all the compounds studied defined as minus the enthalpy change of the
      reaction M+H(+)--> MH(+) (gas state) were calculated. Basicity relative to
      pyridine (DeltaH(rPy)) defined as the enthalpy change of the isodesmic reaction
      MH(+) + Py--> M + PyH(+) (gas state) was also calculated. The effect of bromine
      as substituent on the properties of the beta-carboline moiety in nor-harmane,
      harmane and harmine is discussed.

PMID- 15963436
TI  - Ultraviolet photodegradation of folic acid.
AB  - The vitamin folate is vital for all living creatures. Scientists have suggested
      that ultraviolet degradation of folate in vivo played a role in the evolution of
      mankind. In order to better understand the photodegradation of folate, we have
      provided a spectroscopic study of the ultraviolet photodegradation of aqueous
      folic acid under aerobic conditions. We found strong indications that the folic
      acid molecule is cleaved into p-aminobenzoyl-L-glutamic acid and 6-formyl pterin
      when exposed to ultraviolet radiation. When the irradiation continues, 6-formyl
      pterin is degraded to pterin-6-carboxylic acid. The photodegradation of folic
      acid is divided into three phases. In the first phase, the formation of
      photoproducts follows a zero order rate law. In the second phase the presence of
      photoproducts sensitizes the degradation of folic acid and the degradation
      process is accelerated. In the third phase the degradation of 6-formyl pterin to
      pterin-6-carboxylic acid is the dominating process. This reaction follows a first
      order rate law. We show that both 6-formyl pterin and pterin-6-carboxylic acid
      sensitize the photodegradation of folic acid. However, experiments performed in
      heavy water indicate that generation of singlet oxygen is probably not the
      explanation for the photosensitizing of folic acid.

PMID- 15963437
TI  - Photodynamic activity of dibiotinylated aluminum sulfophthalocyanine in vitro and
      in vivo.
AB  - The photodynamic activity of dibiotinylated aluminum sulfophthalocyanine was
      studied in vitro and in vivo. Dibiotinylated aluminum sulfophthalocyanine
      provided enhanced phototoxic action on OAT-75 cell monolayers as compared with
      the parent drug. Photodynamic therapy of mice with Ehrlich carcinoma using
      dibiotinylated aluminum sulfophthalocyanine (0.25 mg/kg) resulted in enhanced
      inhibition of tumor growth, pronounced vascular damage (thrombosis and
      destruction of vascular walls) and eventual tumor necrosis.

PMID- 15963438
TI  - Photostability and photoprotection factor of boldine and glaucine.
AB  - Boldine hydrochloride was more photounstable than boldine after irradiation with
      UVB (lambda = 300 nm). However, photoconsumption quantum yields, for glaucine
      hydrochloride (6.5 x 10(-2)) and boldine hydrochloride (6.7 x 10(-2)) in air,
      were quite similar. The photolysis was oxygen dependent in both cases, and the
      effect over the kinetics after the addition of 2,2,6,6-tetramethyl-1
      piperidinyloxy suggested free radicals participation. The fact that the
      antioxidative capacity of boldine and boldine hydrochloride did not change during
      the photolysis, suggests that the phenolic structure remains unchanged in the
      photoproducts, corroborated with the photoproducts analysis. The photoprotection
      capacity was evaluated before and after irradiation. Results indicate that the
      values before irradiation are similar for all three compounds, only glaucine
      increasing its capacity with length of irradiation time.

PMID- 15963439
TI  - Remission, intractability, and antiepileptic-drug withdrawal.

PMID- 15963440
TI  - Cardiovascular risk factors associated with migraine.

PMID- 15963442
TI  - Diagnosis of multifocal motor neuropathy.

PMID- 15963443
TI  - Immune response to immunotherapy: the role of neutralising antibodies to
      interferon beta in the treatment of multiple sclerosis.
AB  - Interferon beta was the first therapy to be approved for the treatment of
      relapsing-remitting multiple sclerosis (MS) more than 10 years ago. Interferon
      beta reduces relapse rates and disease burden and activity, and it may have
      beneficial effects on the progression of long-term disease disability. The
      occurrence of neutralising interferon-beta antibodies has been postulated as a
      possible cause of the failure of interferon beta in some patients with MS. Here
      we discuss the basic mechanisms that may account for the generation of an
      interferon-beta antibody response and its biological implications. We review the
      evidence for neutralising antibodies as a consequence of interferon-beta
      treatment, and discuss the implications for the treatment of MS. Strategies to
      assess and manage the long-term impact of neutralising antibodies will be
      outlined.

PMID- 15963444
TI  - Surgery for malignant gliomas: mechanistic reasoning and slippery statistics.
AB  - Current surgical treatment of malignant gliomas largely depends on mechanistic
      reasoning and data collected in non-randomised studies. Technological advance has
      enabled more accurate resection of tumours and preservation of eloquent brain
      areas but ethical considerations have restricted randomised trials on the
      efficacy of surgery to one small trial that found a 3 month survival advantage
      for patients over age 65 years who received surgery and interim analysis of a
      larger trial. There is an argument for surgery as a palliative measure in
      patients with symptoms caused by mechanisms that are surgically remediable.
      Whether there is any survival advantage from surgery in patients other than those
      with immediately life-threatening, surgically remediable complications, such as
      raised intracranial pressure, is unclear. The available data show that if such an
      advantage does exist, it is modest at best. Adjuvant treatments given surgically
      are being studied. Chemotherapy wafers are the most prominent of the adjuvant
      treatments but the evidence available is insufficient to recommend their use in
      routine practice. In this review we examine the prevailing mechanistic model and
      observational data; we assess how these are applied and the priorities they
      indicate for future research.

PMID- 15963445
TI  - Striatal deformities of the hand and foot in Parkinson's disease.
AB  - Striatal deformities of the hand and foot are abnormal postures that are common
      in patients with advanced Parkinson's disease (PD); they can present in the early
      stages of PD and in other parkinsonian disorders. Over a century ago, Charcot and
      Purves-Stewart recognised these deformities, which cause substantial functional
      disability and discomfort. The term striatal is used because pathology in the
      neostriatum (putamen and caudate) has been suggested to cause the deformities,
      but the pathogenesis is unknown. Misdiagnosis of the deformities is common
      particularly when they occur early and in the absence of cardinal parkinsonian
      signs, such as tremor, bradykinesia, and rigidity-because the hand deformities
      are similar to those in rheumatoid arthritis, equinovarus foot deformity
      typically suggests an orthopaedic problem, and toe extension may be thought to be
      the Babinski sign of upper-motor-neuron syndromes. Here we review the background
      and clinical features of these deformities to highlight these commonly
      unrecognised and poorly understood parkinsonian signs.

PMID- 15963446
TI  - In pursuit of evidence-based treatments for paediatric stroke: the UK and Chest
      guidelines.
AB  - BACKGROUND: Arterial ischaemic stroke and cerebral sinovenous thrombosis are
      increasingly seen in infants and children. Incidence ranges from two to six per
      100,000 children a year. Adverse outcome including death, neurological deficits,
      and reduced quality of life affect most children with stroke. Residual
      neurological deficits last many decades, for the rest of a patient's life. Of
      major concern is the risk of recurrent stroke, which affects up to 25% of
      children who have arterial ischaemic stroke after the newborn period. Children
      with ischaemic stroke are empirically treated with antithrombotics including
      antiplatelet (aspirin and clopidogrel) and anticoagulant (heparins and warfarin)
      drugs. No randomised controlled trials have been done besides those in patients
      with sickle-cell disease and adult trial data are not directly applicable to
      paediatric stroke due to maturational differences in coagulation and vascular
      systems as well as different stroke mechanisms. RECENT DEVELOPMENTS: National and
      international networks of clinical and basic researchers focused on paediatric
      stroke are now developing. Recently published cohort and case-controlled studies
      are elucidating stroke mechanisms, outcomes, and treatment safety in children.
      Two sets of guidelines have been published in the past 6 months. These guidelines
      differ both in the scope of treatments and subgroups of patients with stroke they
      cover; however, both focus on ischaemic stroke beyond the newborn period. There
      are areas of agreement-for children with sickle-cell disease and stroke, both
      guidelines recommend initial and maintenance transfusion therapy to reduce the
      proportion of sickle-cell haemoglobin to less than 30%. For children with
      sinovenous thrombosis or arterial stroke due to dissection or cardiac embolism,
      both guidelines recommend anticoagulant therapy with warfarin or low molecular
      weight heparin for 3-6 months. However, the guidelines diverge in their
      recommendations for the initial treatment of non-haemorrhagic arterial ischaemic
      stroke, one recommending aspirin and the other 5-7 days of anticoagulants. The
      guidelines also differ in their recommendations for long-term treatment of
      children after arterial ischaemic stroke, one set recommending maintenance
      aspirin in all patients and the other only in children with vasculopathy. These
      differences arise from both a lack of sufficient evidence and the differing views
      of neurologists and haematologists in the treatment of paediatric cerebral
      thrombosis. WHERE NEXT?: Multicentre studies and networks provide increasingly
      precise data regarding mechanisms, outcomes, and treatment safety in paediatric
      stroke. These data and networks will enable clinical trials to address areas of
      divergent opinion and improve the outcome from childhood stroke in the near
      future.

PMID- 15963447
TI  - New insights into transient global amnesia: recent imaging and clinical findings.
AB  - Transient global amnesia (TGA) is one of the most striking syndromes in clinical
      neurology. Despite several new hypotheses concerning TGA pathogenesis-including
      psychological disturbances, personality traits, and hypoxic-ischaemic origin
      associated with venous congestion in memory relevant structures or small vessel
      changes-there is no consensus about the cause. New imaging techniques,
      particularly diffusion-weighted imaging, open up new insights into the location
      of TGA pathology. Studies with dynamic venous duplex sonography confirmed the
      importance of jugular-vein-valve insufficiency. We review these new findings and
      their implications for a better understanding of this remarkable syndrome.
      Although we still do not have all the answers, the use of new imaging modalities,
      neuropsychological findings, and epidemiological data may in future help to
      unravel the origin of TGA.

PMID- 15963448
TI  - Cognitive impairment, aphasia, and seizures in a 51-year-old man.

PMID- 15963449
TI  - Experimental evaluation of hotspot identification methods.
AB  - Identifying crash "hotspots", "blackspots", "sites with promise", or "high risk"
      locations is standard practice in departments of transportation throughout the
      US. The literature is replete with the development and discussion of statistical
      methods for hotspot identification (HSID). Theoretical derivations and empirical
      studies have been used to weigh the benefits of various HSID methods; however, a
      small number of studies have used controlled experiments to systematically assess
      various methods. Using experimentally derived simulated data--which are argued to
      be superior to empirical data, three hot spot identification methods observed in
      practice are evaluated: simple ranking, confidence interval, and Empirical Bayes.
      Using simulated data, sites with promise are known a priori, in contrast to
      empirical data where high risk sites are not known for certain. To conduct the
      evaluation, properties of observed crash data are used to generate simulated
      crash frequency distributions at hypothetical sites. A variety of factors is
      manipulated to simulate a host of 'real world' conditions. Various levels of
      confidence are explored, and false positives (identifying a safe site as high
      risk) and false negatives (identifying a high risk site as safe) are compared
      across methods. Finally, the effects of crash history duration in the three HSID
      approaches are assessed. The results illustrate that the Empirical Bayes
      technique significantly outperforms ranking and confidence interval techniques
      (with certain caveats). As found by others, false positives and negatives are
      inversely related. Three years of crash history appears, in general, to provide
      an appropriate crash history duration.

PMID- 15963450
TI  - Translocation of deltaPKC to mitochondria during cardiac reperfusion enhances
      superoxide anion production and induces loss in mitochondrial function.
AB  - Activation of the delta-isoform of protein kinase C (deltaPKC) by certain
      conditions of oxidative stress results in translocation of the kinase to the
      mitochondria leading to release of cytochrome c and the induction of apoptosis.
      In the current study, the effects of myocardial reperfusion-induced deltaPKC
      translocation on mitochondrial function were assessed. Mitochondria isolated from
      hearts that had undergone ischemia (30 min) followed by reperfusion (15 min)
      exhibited a significant increase in the rate of superoxide anion (O(2)(-))
      generation. This was associated with the translocation of deltaPKC to the
      mitochondria within the first 5 min of reperfusion. deltaPKC translocation
      occurred exclusively during reperfusion and could be mimicked by infusion of
      intact hearts with H(2)O(2) suggesting redox-dependent activation during
      reperfusion. Infusion of a peptide inhibitor (deltaV(1-1)) specific to the delta
      isoform of PKC significantly reduced reperfusion-induced increases in
      mitochondrial O(2)(-) generation. Finally, the decline in mitochondrial
      respiratory activity evident upon prolonged reperfusion (120min) was completely
      prevented by inhibition of deltaPKC translocation. Thus, deltaPKC represents a
      cytosolic redox-sensitive molecule that plays an important role in amplification
      of O(2)(-) production and subsequent declines in mitochondrial function during
      reperfusion.

PMID- 15963451
TI  - Involvement of phospholipid, biomembrane integrity, and NO peroxidase activity in
      the NO catabolism by cytochrome c oxidase.
AB  - The physiological regulation of mitochondrial respiration by NO has been reported
      to result from the reversible binding of NO to the two-electron reduced binuclear
      center (Fe(2+)(a3)-Cu(1+)(B)) of cytochrome c oxidase (CcO). Although the role of
      CcO and its derived catalytic intermediates in the catabolism of NO has been
      documented, little has been established for the enzyme in its fully oxidized
      state (Fe(3+)(a3)-Cu(2+)(B)). We report: (1) CcO, in its fully oxidized state,
      represents the major component of the mitochondrial electron transport chain for
      NO consumption as controlled by the binding of NO to its binuclear center.
      Phospholipid enhances NO consumption by fully oxidized CcO, whereas the
      consumption of NO is slowed down by membrane structure and membrane potential
      when CcO is embedded in the phospholipid bilayer. (2) In the presence of
      H(2)O(2), CcO was shown to serve as a mitochondria-derived NO peroxidase. A CcO
      derived protein radical intermediate was induced and involved in the modulation
      of NO catabolism.

PMID- 15963452
TI  - Liposome composition effects on lipid mixing between cells expressing influenza
      virus hemagglutinin and bound liposomes.
AB  - The involvement of contacting and distal lipid monolayers in different stages of
      protein-mediated fusion was studied for fusion mediated by influenza virus
      hemagglutinin. Inclusion of non-bilayer lipids in the composition of the
      liposomes bound to hemagglutinin-expressing cells affects fusion triggered by low
      pH. Lysophosphatidylcholine added to the outer membrane monolayers inhibits
      fusion. The same lipid added to the inner monolayer of the liposomes promotes
      both lipid and content mixing. In contrast to the inverted cone-shaped
      lysophosphatidylcholine, lipids of the opposite effective shape, oleic acid or
      cardiolipin with calcium, present in the inner monolayers inhibit fusion. These
      results along with fusion inhibition by a bipolar lipid that does not support
      peeling of one monolayer of the liposomal membrane from the other substantiate
      the hypothesis that fusion proceeds through a local hemifusion intermediate. The
      transition from hemifusion to the opening of an expanding fusion pore allows
      content mixing and greatly facilitates lipid mixing between liposomes and cells.

PMID- 15963453
TI  - Immunohistochemical evaluation of osteoclast recruitment during experimental
      tooth movement in young and adult rats.
AB  - OBJECTIVE: Orthodontic tooth movement starts slower in adults than in juveniles,
      but the rate of tooth movement in later phases is the same in both age groups.
      The hypotheses to be tested are that these phenomena are related to slower
      osteoclast recruitment in adults than in juveniles, but that in later phases the
      osteoclast numbers are the same in both age groups. DESIGN: Standardized
      orthodontic tooth movement was performed in two groups of 30 rats, aged 6 weeks
      and 9-12 months, respectively. All maxillary molars at one side were together
      moved mesially by a continuous force of 10 cN. The other side served as a
      control. After 1, 2, 4, 8 and 12 weeks, groups of animals were killed. After ED1
      staining osteoclast numbers at the mesial and distal sides of selected roots were
      counted. RESULTS: At the compression sides osteoclast numbers increased in both
      age groups. In young rats, a maximum was reached at 2 weeks, in adults at 4
      weeks. In later phases of tooth movement, the number of osteoclasts in the adults
      was approximately twice as high as in the juveniles, while the rate of tooth
      movement was the same. A positive correlation between the rate of tooth movement
      and osteoclast numbers was found only in young rats. CONCLUSIONS: Orthodontic
      forces induce faster osteoclast recruitment in young than in adult rats and more
      osteoclasts are needed to achieve a certain rate of tooth movement in adult than
      in young rats.

PMID- 15963454
TI  - Pressure transmission across dentine in response to an external pressure: a
      laboratory study.
AB  - PURPOSE: To determine whether transducers could provide a convenient method of
      measuring dentine permeability and to investigate the effects of removal of pulp
      tissue and perfusion time on the pressure increase across human dentine after low
      pressure perfusion. METHOD: Human premolar teeth that had been stored for 1-2
      months were prepared for full crown preparations. The pulp tissue was removed
      from half the samples and all the coronal segments perfused with saline at 1.3kPa
      for varying times. An external pressure was then applied and the response within
      the pulp chambers recorded with transducers. RESULTS: Extirpation of pulp tissue
      reduced the rate of rise of pressure inside the pulp chamber by approximately
      50%. Perfusion at 1.3kPa for up to 1h had no effect on pressure rise, but 6h of
      perfusion produced a very significant increase. CONCLUSION: Transducers can
      provide a relatively simple, convenient and clinically relevant measurement of
      dentine permeability. For stored coronal segments that have been perfused at
      physiological pressures, extirpation of pulp tissue and perfusion time have
      significant effects on pressure transmission across dentine.

PMID- 15963455
TI  - The structure of DNA-DOPC aggregates formed in presence of calcium and magnesium
      ions: a small-angle synchrotron X-ray diffraction study.
AB  - The structure of aggregates formed due to DNA interaction with
      dioleoylphosphatidylcholine (DOPC) vesicles in presence of Ca(2+) and Mg(2+)
      cations was investigated using synchrotron small-angle X-ray diffraction. For
      DOPC/DNA=1:1 mol/base and in the range of concentration of the cation(2+) 0-76.5
      mM, the diffractograms show the coexistence of two lamellar phases: L(x) phase
      with repeat distance d(Lx) approximately 8.26-7.39 nm identified as a phase where
      the DNA strands are intercalated in water layers between adjacent lipid bilayers,
      and L(DOPC) phase with repeat distance d(DOPC) approximately 6.45-5.65 nm
      identified as a phase of partially dehydrated DOPC bilayers without any divalent
      cations and DNA strands. The coexistence of these phases was investigated as a
      function of DOPC/DNA molar ratio, length of DNA fragments and temperature. If the
      amount of lipid increases, the fraction of partially dehydrated L(DOPC) phase is
      limited, depends on the portion of DNA in the sample and also on the length of
      DNA fragments. Thermal behaviour of DOPC+DNA+Ca(2+) aggregates was investigated
      in the range 20-80 degrees C. The transversal thermal expansivities of both
      phases were evaluated.

PMID- 15963456
TI  - Structure and thermotropic phase behaviour of detergent-resistant membrane raft
      fractions isolated from human and ruminant erythrocytes.
AB  - Detergent-resistant membrane raft fractions have been prepared from human, goat,
      and sheep erythrocyte ghosts using Triton X-100. The structure and thermotropic
      phase behaviour of the fractions have been examined by freeze-fracture electron
      microscopy and synchrotron X-ray diffraction methods. The raft fractions are
      found to consist of vesicles and multilamellar structures indicating considerable
      rearrangement of the original ghost membrane. Few membrane-associated particles
      typical of freeze-fracture replicas of intact erythrocyte membranes are observed
      in the fracture planes. Synchrotron X-ray diffraction studies during heating and
      cooling scans showed that multilamellar structures formed by stacks of raft
      membranes from all three species have d-spacings of about 6.5 nm. These
      structures can be distinguished from peaks corresponding to d-spacings of about
      5.5 nm, which were assigned to scattering from single bilayer vesicles on the
      basis of the temperature dependence of their d-spacings compared with the
      multilamellar arrangements. The spacings obtained from multilamellar stacks and
      vesicular suspensions of raft membranes were, on average, more than 0.5 nm
      greater than corresponding arrangements of erythrocyte ghost membranes from which
      they were derived. The trypsinization of human erythrocyte ghosts results in a
      small decrease in lamellar d-spacing, but rafts prepared from trypsinized ghosts
      exhibit an additional lamellar repeat 0.4 nm less than a lamellar repeat
      coinciding with rafts prepared from untreated ghosts. The trypsinization of sheep
      erythrocyte ghosts results in the phase separation of two lamellar repeat
      structures (d=6.00; 5.77 nm), but rafts from trypsinized ghosts produce a
      diffraction band almost identical to rafts from untreated ghosts. An examination
      of the structure and thermotropic phase behaviour of the dispersions of total
      polar lipid extracts of sheep detergent-resistant membrane preparations showed
      that a reversible phase separation of an inverted hexagonal structure from
      coexisting lamellar phase takes place upon heating above about 30 degrees C. Non
      lamellar phases are not observed in erythrocytes or detergent-resistant membrane
      preparations heated up to 55 degrees C, suggesting that the lamellar arrangement
      is imposed on these membrane lipids by interaction with non-lipid components of
      rafts and/or that the topology of lipids in the erythrocyte membrane survives
      detergent treatment.

PMID- 15963457
TI  - Are "obsessive" beliefs specific to OCD?: a comparison across anxiety disorders.
AB  - Cognitive models of obsessive-compulsive disorder (OCD) assign a central role to
      maladaptive beliefs about threat, uncertainty, importance and control of
      thoughts, responsibility, and perfection. Previous research has demonstrated that
      such beliefs relate to specific OCD symptoms in a theoretically meaningful way.
      The aim of the present study was to determine whether these beliefs are endorsed
      more strongly by OCD patients than by those with other anxiety disorders. Eighty
      nine adult OCD patients, 72 anxious control (AC) patients, and 33 nonclinical
      control (NCC) participants completed a measure of obsessive beliefs as well as
      measures of depression and trait anxiety. Compared to NCCs and ACs, OCD patients
      more strongly endorsed beliefs related to threat estimation, tolerance of
      uncertainty, importance and control of thoughts, and perfectionism, but not
      inflated responsibility. Using revised, condensed subscales, OCD patients
      differed from ACs on beliefs about perfectionism and certainty and about
      importance and control of thoughts, but not on beliefs about threat estimation
      and inflated responsibility. When controlling for depression and trait anxiety,
      the OCD and AC group did not differ on most belief domains, except for a belief
      that it is possible and necessary to control one's thoughts. Results are
      discussed in light of evolving cognitive-behavioral theories that highlight
      appraisals of thought control and the use and effectiveness of varying thought
      control strategies.

PMID- 15963458
TI  - A cell line model for the differentiation of human dendritic cells.
AB  - We have identified human monocytic (THP-1) and myelogenous CD34+ (KG-1) leukemia
      cell lines that can be differentiated rapidly into mature dendritic cells (DCs)
      when cultured in serum-free medium containing GM-CSF, TNF-alpha, and ionomycin.
      These hematopoietic cell line-derived DCs are highly pure and monotypic, and
      display the morphologic, phenotypic, molecular, and functional properties of DCs
      generated from human donor-derived monocytes or CD34+ hematopoietic progenitor
      cells. During differentiation into mature DCs, the cells exhibit de novo cell
      surface expression of CD83, CD80, CD86, CD40, CD206, CD209, CD120a, CD120b, and
      intracellular synthesis of IL-10, increase their endocytotic capacity, and
      acquire characteristic stellate morphology. To further define the cells as DCs,
      cytosolic induction and upregulation of RelB and RelA (p65), transcription
      factors of the NF-kappaB/Rel family essential for differentiation and maturation
      of DCs, as well as upregulation of the immunoproteasome subunits LMP2, LMP7, and
      MECL-1, and the proteasome activator PA28alpha, components essential for
      efficient MHC class I peptide antigen processing, were demonstrated during
      differentiation of the cells. In contrast to the cell lines, the cell line
      derived mature DCs are capable of stimulating allogeneic CD4+ and CD8+ T cells,
      ultimately defining them as potent antigen-presenting cells. The approach to
      differentiate THP-1 and KG-1 cells into immature and mature DCs may serve as an
      experimental model to study molecular events and pathways that govern the
      differentiation of human malignant myeloid precursors, monocytes, and CD34+
      hematopoietic progenitor cells into DCs.

PMID- 15963459
TI  - Homology modeling and substrate binding study of Nudix hydrolase Ndx1 from
      Thermos thermophilus HB8.
AB  - With homology modeling techniques, molecular mechanics, and molecular dynamics
      methods, a 3D structure model of Ndx1 is created and refined. This model is
      further assessed by Profile-3D and ProStat, which confirm that the refined model
      is reliable. With this model, a flexible docking study is performed and the
      result indicates that Glu46, Arg88, and Glu90 are three important determinant
      residues in binding, as they have strong hydrogen bonding interactions and
      electrostatic interactions with Ap6A. In addition, we further find that three
      residues, Ser38, Leu39 and Glu46, coordinate enzyme-bound Mg2+ ions in complex N
      A. The Glu46 is consistent with the experimental results by Iwai et al., and the
      other four residues mentioned above may also play vital roles in catalysis of
      Ndx1.

PMID- 15963460
TI  - Urokinase plasminogen activator receptor is upregulated by Helicobacter pylori in
      human gastric cancer AGS cells via ERK, JNK, and AP-1.
AB  - The gastric pathogen Helicobacter pylori (H. pylori) is suggested to be
      associated with gastric cancer progression. In this study, we investigated the
      effect of H. pylori on urokinase plasminogen activator receptor (uPAR) expression
      which has been known to correlate closely with gastric cancer invasion. H. pylori
      induced the uPAR expression in a time- and concentration-dependent manner.
      Specific inhibitors and inactive mutants of MEK-1 and JNK were found to suppress
      the H. pylori-induced uPAR expression and the uPAR promoter activity.
      Electrophoretic mobility shift assay and transient transfection study using an AP
      1 decoy oligonucleotide confirmed that the activation of AP-1 is involved in the
      H. pylori-induced uPAR upregulation. The AGS cells treated with H. pylori showed
      a remarkably enhanced invasiveness, and this effect was partially abrogated by
      uPAR-neutralizing antibodies. These results suggest that H. pylori induces uPAR
      expression via Erk-1/2, JNK, and AP-1 signaling pathways and, in turn, stimulates
      the cell invasiveness in human gastric cancer AGS cells.

PMID- 15963461
TI  - 1.88 A crystal structure of the C domain of hCyP33: a novel domain of peptidyl
      prolyl cis-trans isomerase.
AB  - Cyclophilins (CyPs) are a widespreading protein family in living organisms and
      possess the activity of peptidyl-prolyl cis-trans isomerase (PPIase), which is
      inhibited by cyclosporin A (CsA). The human nuclear cyclophilin (hCyP33) is the
      first protein which was found to contain two RNA binding domains at the amino
      terminus and a PPIase domain at the carboxyl-terminus. We isolated the hCyP33
      gene from the human hematopoietic stem/progenitor cells and expressed it in
      Escherichia coli, and determined the crystal structure of the C domain of hCyP33
      at 1.88 A resolution. The core structure is a beta-barrel covered by two alpha
      helices. Superposition of the structure of the C domain of hCyP33 with the
      structure of CypA suggests that the C domain contains PPIase active site which
      binds to CsA. Furthermore, C domain seems to be able to bind with the Gag-encoded
      capsid (CA) of HIV-1 and may affect the viral replication of HIV-1. A key residue
      of the active site is changed from Ala-103-CypA to Ser-239-hCyP33, which may
      affect the PPIase domain/substrates interactions.

PMID- 15963462
TI  - Phosphorylation and binding partner analysis of the TSC1-TSC2 complex.
AB  - Tuberous sclerosis complex (TSC) is an autosomal dominant benign tumour syndrome
      caused by mutations to either the TSC1 or TSC2 tumour suppressor gene. The TSC1
      and TSC2 gene products, TSC1 and TSC2, form a protein complex that integrates
      inputs from multiple signalling cascades to inactivate the small GTPase rheb, and
      thereby inhibit mTOR-dependent cell growth. We have used matrix-assisted laser
      desorption/ionisation time-of-flight and Fourier transform mass spectrometry to
      identify TSC1 and TSC2 phosphorylation sites and candidate TSC1 and TSC2
      interacting proteins. We identified three sites of TSC2 phosphorylation and a
      novel site of TSC1 phosphorylation, and investigated the roles of these sites in
      regulating the activity of the TSC1-TSC2 complex. In addition, we identified
      three TSC1-TSC2 interacting proteins, including DOCK7 a putative rhebGEF.

PMID- 15963463
TI  - Hydrogen peroxide and peroxynitrite enhance Ca2+ mobilization and aggregation in
      platelets from type 2 diabetic patients.
AB  - Cytosolic Ca2+ mobilization, especially Ca2+ entry, is enhanced in platelets from
      type 2 diabetic individuals, which might result in platelet hyperaggregability.
      In the present study, we report an increased oxidant production in resting and
      stimulated platelets from diabetic donors. Pretreatment of platelets with
      catalase or trolox, an analog of vitamin E, reversed the enhanced Ca2+ entry,
      evoked by thapsigargin plus ionomycin or thrombin, observed in platelets from
      diabetic subjects, so that in the presence of these scavengers Ca2+ entry was
      similar in platelets from healthy and diabetic subjects. In contrast, mannitol
      was without effect on Ca2+ mobilization. Catalase and trolox reduced thrombin
      induced aggregation in platelets from type 2 diabetic subjects, while mannitol
      did not modify thrombin-induced platelet hyperaggregability. We conclude that
      H2O2 and ONOO- are likely involved in the enhanced Ca2+ mobilization observed in
      platelets from type 2 diabetic patients, which might lead to platelet
      hyperactivity and hyperaggregability.

PMID- 15963464
TI  - Paraoxonase-1 and linoleic acid oxidation in familial hypercholesterolemia.
AB  - Serum paraoxonase-1 (PON1) is a high-density lipoprotein-associated enzyme that
      can inhibit low-density lipoprotein (LDL) oxidation in vitro. The role of PON1 in
      vivo still remains to be clarified. We investigated the effect of PON1 genotype (
      107C > T and 192Q > R), concentration, paraoxonase activity, and arylesterase
      activity on the early phase of lipid peroxidation in plasma samples of 110
      patients with heterozygous familial hypercholesterolemia. The degree of lipid
      oxidation was assessed by quantitation of oxidized-linoleic acid (the most
      abundant fatty acid present in LDL) using high performance liquid chromatography.
      We found a significant inverse correlation between paraoxonase activity and the
      oxidized-linoleic acid concentration (r = -0.22, P = 0.03), independent of
      baseline linoleic acid levels. These findings support an anti-oxidative role for
      PON1 in patients with FH, and thus may give insight into the functioning of PON1
      in vivo.

PMID- 15963465
TI  - Characterization of the organic cation transporter SLC22A16: a doxorubicin
      importer.
AB  - Specific efflux transporters, such as P-glycoprotein, have been shown to confer
      drug resistance by decreasing the intracellular accumulation of anticancer drugs.
      Understanding influx transporters, as well as efflux transporters, is essential
      to overcome this resistance. We report the expression profile and pharmacological
      characterization of an organic cation transporter, SLC22A16. The results of our
      experiments indicate that SLC22A16 is a mediator of doxorubicin uptake in cancer
      cells. Quantitative real-time RT-PCR analyses show that SLC22A16 is expressed in
      primary samples taken from patients with acute leukemia. Xenopus oocytes injected
      with SLC22A16 cRNA import doxorubicin, a widely used anticancer drug for
      hematological malignancies, in a saturable and dose-dependent manner. The
      apparent Km value for doxorubicin import was 5.2+/-0.4 microM. In cytotoxic
      assays, stable transfectants of leukemic Jurkat cells overexpressing SLC22A16
      cells became significantly more sensitive to doxorubicin (2 microM) treatment.
      Characterization of SLC22A16 will help in designing novel therapies targeting
      hematological malignancies.

PMID- 15963466
TI  - Testicular type Sox9 is not involved in sex determination but might be in the
      development of testicular structures in the medaka, Oryzias latipes.
AB  - Testicular type Sox9 is the most upstream conserved gene in the sex determining
      cascade among vertebrate. However, in medaka, only one Sox9 gene was identified
      as expressed in the ovary; no other Sox9 gene was reported expressed in the
      testis. We explored the medaka genome and cloned a novel testicular type Sox9
      cDNA. Phylogenetic analysis revealed that both our isolated Sox9 and the already
      reportedly cloned medaka Sox9 belongs zebrafish Sox9a branch. Therefore, we named
      our gene Sox9a2. Unexpectedly, Sox9a2 mRNA was expressed in somatic cells
      surrounding germ cells at similar high levels in both sexes during early gonadal
      sex differentiation. However, at the initial stage of testicular tubules
      development, the expression of Sox9a2 was maintained only in XY gonads, and was
      remarkably reduced in XX gonads. These results suggest that Sox9a2 is not
      involved in early sex determination and differentiation, but is involved in the
      later development of testicular tubules in medaka.

PMID- 15963467
TI  - Functional VEGF C-634G polymorphism is associated with development of diabetic
      macular edema and correlated with macular retinal thickness in type 2 diabetes.
AB  - Since vascular endothelial growth factor (VEGF) has a strong effect on induction
      of vascular permeability, VEGF is an attractive candidate gene for development of
      diabetic macular edema (ME). Among the 378 patients with type 2 diabetes studied,
      203 patients had no retinopathy, 93 had non-proliferative diabetic retinopathy
      (NPDR), and 82 had proliferative diabetic retinopathy (PDR). ME was present in 16
      patients with NPDR and 47 patients with PDR. We genotyped three VEGF
      polymorphisms: C-2,578A, G-1,154A, and C-634G. Genotype and allele distribution
      of C-634G, but not C-2,578A or G-1,154A, were significantly different between
      patients with and without diabetic retinopathy. Logistic regression analysis
      revealed that the C-634G genotype was a risk factor for DR (p = 0.002), and
      furthermore for ME (p = 0.047), independently from severity of DR, with the -634C
      allele increasing the risk. Macular thickness measured by optical coherence
      tomography was correlated with the C-634G genotype, with the trend increasing
      with the presence of more -634C alleles (p = 0.006). Stepwise regression analysis
      showed that duration of diabetes and presence of the C-634G genotype were
      independent predictors of macular thickness. In addition, basic transcriptional
      activity levels associated with the -634C allele were greater compared to those
      seen with the -634G allele in human glioma and lymphoblastic T-lymphocyte cells.
      These results demonstrate that the VEGF C-634G polymorphism is a genetic risk
      factor for ME as well as DR.

PMID- 15963468
TI  - A prothrombin activator (Lopap) modulating inflammation, coagulation and cell
      survival mechanisms.
AB  - A severe hemorrhagic syndrome produced by contact with Lonomia obliqua
      caterpillars has become epidemic in southern Brazil. A significant thrombin
      production with intense consumption of fibrinogen and high D-dimer production
      indicates a consumption coagulopathy and secondary fibrinolysis in patients.
      Lopap is a single-chain 69kDa serine protease isolated from the crude extract of
      L. obliqua bristles. Experiments in mice showed that the purified protein,
      similar to the crude extract, causes uncoagulable blood by fibrinogen depletion.
      In order to characterize the effects of Lopap on cells involved with hemostatic
      system, we performed experiments using human umbilical vein endothelial cells
      (HUVECs). Our results show that Lopap exerts a direct effect on endothelial cells
      by increasing the liberation of molecules involved in the regulation of vascular
      tone, inhibiting platelet activation and chemotaxis, apart from inducing the
      expression of cell adhesion molecules which participate in inflammatory
      responses. The release or new synthesis of mediators involved in coagulation as
      von Willebrand factor and tissue factor, or in fibrinolysis as tissue plasminogen
      activator, was not affected by Lopap. Also our results demonstrated that Lopap
      acts on cell survival of HUVECs, regulating the expression of molecules as NO and
      avoiding cell death.

PMID- 15963469
TI  - Structural comparison of yeast snoRNP and spliceosomal protein Snu13p with its
      homologs.
AB  - Snu13p is a bifunctional yeast protein involved in both messenger RNA splicing as
      well as ribosomal RNA maturation. Snu13p initiates assembly of ribonucleoprotein
      particles by interacting with a conserved RNA motif called kink turn. Unlike its
      archaeal homolog, L7Ae, Snu13p displays differential specificity for functionally
      distinct kink turns. Thus, the structures of Snu13p at different functional
      states, including those alone and bound with RNAs, are required to understand how
      the protein differentially interacts with kink turns. Although the structure of
      the human homolog of Snu13p bound with a spliceosomal RNA is known, there has not
      been a report of a structure of free Snu13p. This has hindered our ability to
      understand the structural basis for Snu13p's substrate specificity. We report a
      crystal structure of free Snu13p at 1.9A and a detailed structural comparison
      with its homologs. We show that free Snu13p has nearly an identical conformation
      as that of its human homolog bound with RNA. Interestingly, both eukaryotic
      proteins exhibit notable structural differences in their central beta-sheets as
      compared to their archaeal homolog, L7Ae. The observed structural differences
      offer a possible explanation to the observed difference in RNA specificity
      between Snu13p and L7Ae.

PMID- 15963470
TI  - Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase
      and topoisomerase activities and human cancer cell proliferation.
AB  - Conjugated eicosapentaenoic acid (cEPA) selectively inhibited the activities of
      mammalian DNA polymerases (pols) and human DNA topoisomerases (topos) [Yonezawa
      Y, Tsuzuki T, Eitsuka T, Miyazawa T, Hada T, Uryu K, et al. Inhibitory effect of
      conjugated eicosapentaenoic acid on human DNA topoisomerases I and II. Arch
      Biochem Biophys 2005;435:197-206]. In this report, we investigated the inhibitory
      effect of cEPA on a human promyelocytic leukemia cell line, HL-60, to determine
      which enzymes influence cell proliferation. cEPA inhibited the proliferation of
      HL-60 cells (LD(50)=20.0 microM), and the inhibitory effect was stronger than
      that of non-conjugated EPA. cEPA arrested the cells at G1/S-phase, increased
      cyclin A and E protein levels, and prevented the incorporation of thymidine into
      the cells, indicating that it blocks the primary step of in vivo DNA replication
      by inhibiting the activity of replicative pols rather than topos. This compound
      also induced apoptosis of the cells. These results suggested the therapeutic
      potential of cEPA as a leading anti-cancer compound that poisons pols.

PMID- 15963471
TI  - Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human
      aortic smooth muscle cells.
AB  - Thiazolidinediones are a new class of anti-diabetic agents which increase insulin
      sensitivity by binding to the peroxisome proliferator-activated receptor gamma
      (PPAR(gamma)) and stimulating the expression of insulin-responsive genes involved
      in glucose and lipid metabolism. These drugs also have vasodilatory and anti
      proliferative effects on vascular smooth muscle cells. However the mechanisms for
      these actions are not fully understood. Adenosine is a vasodilator and a
      substrate of equilibrative nucleoside transporters (ENT). The present study
      studied the effects of three thiazolidinediones, troglitazone, pioglitazone and
      ciglitazone, on ENT1 in the human aortic smooth muscle cells (HASMCs). Although
      incubating HASMCs for 48h with thiazolidinediones had no effect on ENT1 mRNA and
      protein levels, troglitazone acutely inhibited [3H]adenosine uptake and [3H]NBMPR
      binding of HASMCs with IC50 values of 2.35+/-0.35 and 3.99+/-0.57microM,
      respectively. The effect of troglitazone on ENT1 was PPAR(gamma)-independent and
      kinetic studies revealed that troglitazone was a competitive inhibitor of ENT1.
      In contrast, pioglitazone and ciglitazone had minimal effects on [3H]adenosine
      uptake by HASMCs. Troglitazone differs from pioglitazone and ciglitazone in that
      its side-chain contains a Vitamin E moiety. The difference in structure of
      troglitazone did not account for its inhibitory effect on ENT1 because Vitamin E
      did not inhibit [3H]adenosine uptake by HASMCs. Using the nucleoside transporter
      deficient PK15NTD cells stably expressing ENT1 and ENT2, it was found that
      troglitazone inhibited ENT1 but had no effect on ENT2. From these results, it is
      suggested that troglitazone may enhance the vasodilatory effect of adenosine by
      inhibiting ENT1. Pharmacologically, troglitazone is a novel inhibitor of ENT1.

PMID- 15963472
TI  - Effect of repeated systemic administration of selective inhibitors of
      endocannabinoid inactivation on rat brain endocannabinoid levels.
AB  - Several selective inhibitors of endocannabinoid inactivation via either the fatty
      acid amide hydrolase (FAAH) or the putative endocannabinoid transporter have been
      developed so far. Here, we have studied the effect in rats of a subchronic
      intraperitoneal treatment with three recently developed selective inhibitors of
      endocannabinoid uptake (VDM-11, UCM-707 and OMDM-2) or with a selective FAAH
      inhibitor (N-arachidonoyl-serotonin, AA-5-HT), on the brain levels of anandamide
      and 2-arachidonoylglycerol (2-AG) measured by means of isotope dilution LC-MS 1,
      5 and 12 h after the last treatment. OMDM-2 was the most efficacious compound at
      enhancing the levels of anandamide at all time points, with a maximal effect (1.9
      fold enhancement) after 5h. This compound also enhanced 2-AG levels by
      approximately 1.3-fold, but only 5 and 12h from administration. VDM-11 slightly,
      albeit significantly, enhanced anandamide levels (1.3-fold) only at 1h from
      administration and 2-AG levels (1.3-fold) only after 5h. Finally, UCM-707 only
      affected 2-AG levels (by two-fold) at only 1h from administration. FAAH
      inhibition by AA-5-HT significantly enhanced the levels of both anandamide
      (between 1.3- and 1.5-fold, maximal effect after 1 h) and 2-AG (between 1.3- and
      1.6-fold, maximal effect after 12 h) at all time points. Brains from rats treated
      with AA-5-HT did never exhibit enhanced levels of serotonin, thus pointing to the
      metabolic stability of this FAAH inhibitor. These data indicate that: (1) the
      pharmacological effects reported so far for the four compounds under study in
      animal models of diseases may be due to enhancement of both anandamide and 2-AG
      levels; (2) 2-AG seems to need a longer time after the last administration in
      order to be augmented; (3) OMDM-2 and AA-5-HT should be regarded as enhancers of
      endocannabinoid levels suitable for use in vivo.

PMID- 15963473
TI  - Dissociated glucocorticoids equipotently inhibit cytokine- and cAMP-induced
      matrix degrading proteases in rat mesangial cells.
AB  - Dissociated glucocorticoids are synthetic ligands of the glucocorticoid receptor
      (GR) and which discriminate between transrepression and transactivation. These
      compounds were predicted to have large therapeutic benefits when compared to
      conventional glucocorticoids because of reduced side effects. In this study, we
      compared the transrepressive properties of different dissociated glucocorticoids
      on the interleukin-1beta (IL-1beta)-activated metalloproteinase-9 (MMP-9) and
      tissue plasminogen activator (tPA) expression in rat mesangial cells (MC). Both
      proteinases regulate the turnover of extracellular matrix (ECM). We demonstrate
      that the GR agonist RU 24858, equipotent to dexamethasone (DEX), exhibited strong
      suppressive effects on the IL-1beta-induced MMP-9 and tPA mRNA levels concomitant
      with an inhibition of corresponding enzyme activities. In contrast, RU 24782 and
      RU 40066 exhibited weaker inhibitory activities on both proteinases.
      Mechanistically, the changes in MMP-9 expression level by different RUs were
      accompanied by an inhibition of cytokine-induced promoter activity indicating
      that the inhibition occurs on a transcriptional level. In parallel to the
      reduction in mRNA levels, we observed an attenuation of cytokine-induced DNA
      binding of nuclear factor kappa B (NF-kappaB) and reduced contents of the p65
      subunit of NF-kappaB within cell nuclei. Along with these transrepressive
      activities RU 24858, RU 24782 and RU 40066 displayed similar transactivation
      potentials as indicated by induction of the glucocorticoid-inducible mouse
      mammary tumor virus (MMTV) reporter gene and by induced expression level of
      plasminogen activator inhibitor 1 (PAI-1). Interestingly, the different RUs
      affected the expression of cAMP-induced tPA and inducible NO synthase with the
      same potency as the IL-1beta-induced protease expression thus indicating that
      these compounds equipotently modulate cytokine- and cAMP-driven gene expression.

PMID- 15963474
TI  - Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages:
      structure-activity relationship and molecular mechanisms involved.
AB  - The effects of anthocyanidins, the aglycon nucleuses of anthocyanins widely
      occurring in reddish fruits and vegetables, on the expression of cyclooxygenase-2
      (COX-2) were investigated in lipopolysaccharide (LPS)-activated murine macrophage
      RAW264 cells. Of five anthocyanidins, delphinidin and cyanidin inhibited LPS
      induced COX-2 expression, but pelargonidin, peonidin and malvidin did not. The
      structure-activity relationship suggest that the ortho-dihydroxyphenyl structure
      of anthocyanidins on the B-ring appears to be related with the inhibitory
      actions. Delphinidin, the most potent inhibitor, caused a dose-dependent
      inhibition of COX-2 expression at both mRNA and protein levels. Western blotting
      analysis indicated that delphinidin inhibited the degradation of IkappaB-alpha,
      nuclear translocation of p65 and CCAAT/enhancer-binding protein (C/EBP)delta and
      phosphorylation of c-Jun, but not CRE-binding protein (CREB). Moreover,
      delphinidin suppressed the activations of mitogen-activated protein kinase (MAPK)
      including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase
      (ERK) and p38 kinase. MAPK inhibitors (U0126 for MEK1/2, SB203580 for p38 kinase
      and SP600125 for JNK) specifically blocked LPS-induced COX-2 expression. Thus,
      our results demonstrated that LPS-induced COX-2 expression by activating MAPK
      pathways and delphinidin suppressed COX-2 by blocking MAPK-mediated pathways with
      the attendant activation of nuclear factor-kappaB (NF-kappaB), activator protein
      1 (AP-1) and C/EBPdelta. These findings provide the first molecular basis that
      anthocyanidins with ortho-dihydroxyphenyl structure may have anti-inflammatory
      properties through the inhibition of MAPK-mediated COX-2 expression.

PMID- 15963475
TI  - Metabolic changes in rat striatum following convulsive seizures.
AB  - Generalized convulsive seizures increase glucose utilization within the brain but
      their impact on metabolism is not well known. The striatum receives excitatory
      input from widespread sources in the brain and could potentially reflect energy
      depletion in the brain resulting from generalized seizures. We utilized
      multiprobe microdialysis in freely moving rats subjected to maximal electroshock
      to simultaneously measure glucose, lactate, and pyruvate levels in the
      interstitial space within striatum and in peripheral subcutaneous tissue. A brief
      convulsive seizure was associated with marked changes in striatal and peripheral
      metabolism during the post-ictal state that lasted up to 1 h. There were
      significant central and peripheral elevations of glucose, pyruvate, and lactate,
      reflecting increased glucose metabolism. Interestingly, the lactate-to-pyruvate
      ratio increased significantly in the periphery but remained unchanged in the
      striatum. Thus, there appears to be brain mechanisms that maintain adequate
      energy sources and prevent anaerobic shift during the post-ictal state.

PMID- 15963476
TI  - (1)H magnetic resonance spectroscopy of autosomal ataxias.
AB  - Multiple forms of autosomal ataxia exist which can be identified by genetic
      testing. Due to their wide variety, the identification of the appropriate genetic
      test is difficult but could be aided by magnetic resonance data. In this study,
      magnetic resonance spectroscopy (MRS) and imaging (MRI) data were recorded for 20
      ataxia patients of six different types and compared to 20 normal subjects.
      Spectra were acquired in the pons, left frontal lobe, left basal ganglia, left
      cerebellar hemisphere and vermis. Both metabolite spectra and absolute metabolite
      concentrations were determined. Differences in metabolite levels were observed
      between ataxia patients and control subjects and between ataxia patients of
      different types. A number of correlations were found between metabolite ratios,
      atrophy levels, number of repeats on the small and large allele, age at
      examination, symptoms duration and age at symptoms onset for ataxia patients.
      These MR characteristics are expected to be useful for the identification of the
      ataxia type.

PMID- 15963477
TI  - Peroxynitrite like Pan?

PMID- 15963478
TI  - Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyopathy due
      to systemic carnitine deficiency.
AB  - OBJECTIVE: 1,2-Diacylglycerol (DAG), a lipid second messenger that activates
      protein kinase C (PKC), is increased with a distinct fatty acid composition in
      the heart of the juvenile visceral steatosis (JVS) mouse, which develops
      pathological cardiac hypertrophy with lipid accumulation induced by the
      perturbation of fatty acid beta-oxidation due to systemic carnitine deficiency.
      Fish oil (FO) may exert its beneficial effects on the cardiomyopathy in JVS mice
      by modifying the molecular species composition of myocardial DAG. To test this
      hypothesis, we investigated the effects of dietary FO on the hypertrophied hearts
      in JVS mice. METHODS: Both control and JVS mice were fed a FO diet (containing
      10% FO) or a standard diet from 4 weeks of age. RESULTS: At 8 weeks of age, the
      ventricular-to-body weight ratio in JVS mice was 2.7-fold higher than that in
      controls (9.9 +/- 0.1 vs. 3.7 +/- 0.1 mg/g, P < 0.01) and was reduced by dietary
      FO (7.7 +/- 0.1 mg/g, P < 0.01 vs. JVS mice). In JVS mice, myocardial DAG levels
      were elevated by 2.3-fold with a distinct fatty acid composition with increases
      in C18:1n-7,9 and C18:2n-6 fatty acids compared with controls; dietary FO had no
      effects on the total DAG levels but significantly altered the fatty acid
      composition of DAG with reduction of both fatty acid species. Immunoblot analysis
      showed that dietary FO prevented the membrane translocation of cardiac PKCs
      alpha, beta2, and epsilon in JVS mice. Dietary FO did not affect the plasma and
      myocardial total carnitine levels in JVS mice. Furthermore, dietary FO
      significantly improved the progressive left ventricular dysfunction and survival
      rate in JVS mice. CONCLUSIONS: Dietary FO may attenuate cardiac hypertrophy with
      improvements in cardiac function and survival in JVS mice via modification of the
      molecular species composition of myocardial DAG and the consequent inhibition of
      PKC redistribution. These results suggest the implication of the molecular
      species composition of DAG in the pathogenesis of lipotoxic cardiomyopathy due to
      perturbations of fatty acid beta-oxidation.

PMID- 15963479
TI  - Involvement of furin-like proprotein convertases in the arterial response to
      injury.
AB  - BACKGROUND: Furin-like proprotein convertases (PCs) are proteolytic activators of
      proproteins, like membrane type 1-matrix metalloproteinase (MT1-MMP) and
      transforming growth factor beta (TGF-beta), that are described in the arterial
      response to injury. However, the involvement of furin-like PCs in the arterial
      response to injury has not been studied yet. We studied furin, MT1-MMP, MMP
      levels and TGF-beta signaling after arterial injury. We also investigated the
      effect of an inhibitor of furin-like PCs, alpha1-antitrypsin Portland (alpha1
      PDX), on arterial injury following balloon dilation. METHODS AND RESULTS: NZW
      rabbit femoral and iliac arteries (N=42) were balloon dilated unilaterally and
      harvested after 2, 7, 14, 28 or 42 days. Furin mRNA levels were increased after 2
      and 7 days. MMP-2 and MT1-MMP levels were increased after day 7 and TGF-beta
      signaling, by phosphorylating Smad 1/5 and 2/3, was increased at all time points.
      Inhibition of furin-like PCs, by adenoviral over-expression of alpha1-PDX,
      blocked proTGF-beta activation and Smad phosphorylation, and reduced MT1-MMP and
      MMP-2 activation (N=5). In vivo adventitial inhibition of furin-like PCs (N=9)
      resulted in a reduction of 13.1+/-5.2% in advential and 23.6+/-7.9% in intimal
      areas (P<0.05), but had no effect on lumen size due to decreased vessel areas.
      CONCLUSIONS: This study demonstrates that furin-like PCs are involved in the
      arterial response to injury possibly through activation of the TGF-beta-Smad
      signaling pathway and identifies furin-like PCs as a possible target to inhibit
      intimal hyperplasia.

PMID- 15963480
TI  - The role of Toll-like receptor signalling in the pathogenesis of arthritis.
AB  - Recent evidence highlighted the role of Toll-like receptors (TLRs) as key
      recognition structures of the innate immune system. The activation of TLRs
      initiates the production of inflammatory cytokines, chemokines, tissue
      destructive enzymes, and type I interferons. In addition, TLR signalling plays an
      important role in the activation and direction of the adaptive immune system by
      the upregulation of costimulatory molecules of antigen presenting cells.
      Considering the important role of TLR signalling as a critical link between
      innate and adaptive immunity it has been proposed that a dysregulation in TLR
      signalling might be associated with autoimmunity. In this review, recent studies
      on TLR signal transduction pathways activated by corresponding ligands are
      summarized and evidence for a possible role of TLR signalling in the pathogenesis
      of rheumatoid arthritis is discussed.

PMID- 15963481
TI  - Neuroglial response after induction of experimental allergic encephalomyelitis in
      susceptible and resistant rat strains.
AB  - Experimental allergic encephalomyelitis (EAE), the animal model for multiple
      sclerosis in humans, a T-cell mediated disease of the central nervous system is
      characterized by inflammatory infiltrates of myelin antigen(s)-specific T cells
      and consecutive demyelination. Spinal cord tissue emulsified in complete Freund's
      adjuvant clinical disease in the genetically susceptible Dark Agouti rats (DA)
      but not in Albino Oxford (AO) rats although similar inflammatory infiltrates in
      the CNS are observed in both strains 10-12 days after induction. We have shown
      that the resistance to clinical disease of AO rats is associated with rapid
      clearance of infiltrating mononuclear cells by a mechanism of apoptosis. Here, we
      demonstrate by immunohistochemical and FACS analyses of the expression of CD11b/c
      that microglial cells respond differently to disease induction in the two
      strains. Whereas microglial cells are activated throughout the period of day 10
      28 days after EAE induction in AO rats they are only activated at the inception
      and resolution phases but not at the peak of clinical disease in DA rats when
      there is the highest level of CD4+ T cell infiltration. Our findings are
      compatible with the notion that microglia terminate effector T cells by apoptosis
      and that lack of this mechanism as evidenced by the lack of CD11b/c expression,
      support T cell survival and clinical expression of disease.

PMID- 15963482
TI  - Association of NKT cells and granulocytes with liver injury after reperfusion of
      the portal vein.
AB  - Reperfusion of the liver was conducted by clamping the portal vein for 30 min in
      mice, followed by unclamping. Unique variation in the number of lymphocytes was
      induced and liver injury occurred thereafter. The major expander cells in the
      liver were estimated to be natural killer T cells (i.e., NKT cells), whereas
      conventional T cells and NK cells increased only slightly or somewhat decreased
      in number and proportion at that time. Reflecting the expansion of NKT cells in
      the liver, a Th0-type of cytokine profile was detected in sera, and cytotoxic
      activity was enhanced in liver lymphocytes. In NKT cell-deficient mice including
      CD1d (-/-) mice and athymic nude mice, the magnitude of liver injury decreased up
      to 50% of that of control mice. It was also suspected that accumulating
      granulocytes which produce superoxides might be associated with liver injury
      after reperfusion. This might be due to stress-associated production of
      catecholamines. It is known that granulocytes bear surface adrenergic receptors
      and that they are activated by sympathetic nerve stimulation after stress. The
      present results therefore suggest that liver injury after reperfusion may be
      mainly caused by the activation of NKT cells and granulocytes, possibly by their
      cytotoxicity and superoxide production, respectively.

PMID- 15963483
TI  - C-type lectin OCILRP2/Clr-g and its ligand NKRP1f costimulate T cell
      proliferation and IL-2 production.
AB  - We are reporting the identification of a novel C-type lectin receptor-ligand pair
      that is involved in T cell costimulation. The receptor, OCILRP2/Clr-g, is rapidly
      induced following T cell activation and maintained at a substantial level of up
      to 72 h. The ligand, NKRP1f, is predominantly expressed on dendritic cells (DC).
      The soluble OCILRP2-Ig blocking protein significantly suppresses specific antigen
      stimulated T cell proliferation as well as IL-2 secretion both in vitro and in
      vivo; conversely, NKRP1f-expressing antigen presenting cells (APC) enhance
      B7.1/CD28-mediated costimulation for T cell proliferation through interaction
      with OCILRP2/Clr-g. Our studies reveal a unique functional interaction between
      two C-type lectins, OCILRP2/Clr-g and NKRP1f, during APC-mediated T cell
      costimulation and suggest a role for C-type lectins in maintaining T cell
      response or memory in vivo.

PMID- 15963484
TI  - Novel missense mutation in the CASR gene in a Chinese family with familial
      hypocalciuric hypercalcemia.
AB  - BACKGROUND: Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant
      disorder characterized by asymptomatic and non-progressive hypercalcemia
      resulting from loss-of-function mutations of the CASR (calcium-sensing receptor)
      gene located on chromosome 3, or from mutations in two mapped but unidentified
      genes located on chromosome 19. METHODS: We report a middle-aged woman
      incidentally found to have FHH. To determine the molecular basis of FHH in this
      Chinese family, we performed direct DNA sequencing of the CASR gene of the
      proband. RESULTS: We found that the proband is heterozygous for a novel missense
      mutation P798T, confirming the diagnosis of FHH. Family screening showed that all
      of the offspring with biochemical features of FHH have the P798T mutation. The
      mutation, P798T, is located in the third intracellular loop of the CASR, possibly
      affecting the downstream calcium sensing pathway and therefore inactivating the
      receptor function. CONCLUSIONS: The molecular basis of FHH in a Chinese family
      was established. The developed mutation detection assay provides a reliable
      method for identifying FHH carriers.

PMID- 15963485
TI  - Improved infrared spectrophotometer for point-of-care patient 13C-urea breath
      testing in the primary care setting.
AB  - The 13C-urea breath test provides non-invasive testing for Helicobacter pylori
      infection with the possibility of analysis at the point of care. Point of care
      tests require accurate and efficient desktop instrumentation. OBJECTIVE: To
      compare results obtained from a new infrared spectrophotometer (10 kg, 2 min
      sample measurement) to the previously approved UBiT-IR300 (22.5 kg, 5-6 min
      sample measurement). DESIGN AND METHODS: Adults underwent urea breath testing;
      breath samples were analyzed using the new and the predicate instruments.
      RESULTS: There were 220 adults enrolled (age range 18-74 years; M/F = 35:65);
      with 86 UBT positive and 134 negative cases. The overall agreement between
      instruments was 99.6% (95% C.I. = 97.6 to 99.9); the positive agreement was 100%.
      CONCLUSION: Technical performance of the new instrument was excellent.

PMID- 15963486
TI  - Validation of a high-performance liquid chromatography method for the measurement
      of mycophenolic acid and its glucuronide metabolites in plasma.
AB  - OBJECTIVES: The need for therapeutic drug monitoring of the immunosuppressant
      mycophenolic acid is becoming more evident. This paper describes a simple high
      performance liquid chromatography procedure for the simultaneous quantitation of
      mycophenolic acid (MPA) and its glucuronide metabolites in plasma using protein
      precipitation followed by HPLC analysis with isocratic elution and UV detection.
      DESIGN AND METHODS: The performance of this method is compared to the EMIT 2000
      MPA immunoassay (Dade Behring Diagnostics Inc., Cupertino, California, USA).
      RESULTS AND CONCLUSION: Intra-assay precision and accuracy of calibrators were
      determined for MPA at 0.5 and 20 mg/L, MPAGe at 5 and 200 mg/L, and MPAGa at 2.5
      and 100 mg/L and showed coefficients of variation of less than 5.0% and biases of
      less than 14.0%. Inter-assay precision and accuracy of quality control samples
      were determined for MPA at 2 and 15 mg/L, MPAGe at 20 and 150 mg/L and showed CVs
      of less than 5.0% and biases of less than 14%. The lower limit of quantitation of
      the method was determined for MPA at 0.25 mg/L, MPAGe at 0.5 mg/L, and MPAGa at
      0.25 mg/L and showed CVs of less than 19% and biases of less than 20%. This
      method, compared to the EMIT 2000 MPA immunoassay, showed a linear regression
      analysis relationship of EMIT = 0.973 HPLC + 0.55 (r(2) = 0.851), and was
      determined to be suitable for therapeutic drug monitoring and pharmacokinetic
      studies of MPA.

PMID- 15963487
TI  - Selection of cryoprotectants based on their toxic effects on oyster gametes and
      embryos.
AB  - Cryopreservation is a valuable tool for aquaculture by providing continuous seed
      production, regardless of the spawning seasons. This study aimed to select the
      least toxic among the cryoprotectants dimethyl sulfoxide (Me2SO), propylene
      glycol (PG), and methanol (MET) based on their toxicological effects on
      Crassostrea rhizophorae gametes and trochophores. They were exposed for 10, 20,
      and 30 min to a range of concentrations of those cryoprotectants. The endpoint
      was EC15-24 h (effective concentration which causes abnormalities in 15% of the
      population exposed to the cryoprotectants for 24 h), recently determined as the
      chronic value (the concentration at which chronic effects are first observed) for
      C. rhizophorae embryonic phases. There were no significant differences (p>0.05)
      among the exposure times in Me2SO toxic effects to either gametes or
      trochophores. For MET, the increase in exposure time resulted in higher toxicity
      for gametes, but not for trochophores, while for PG there was a significant
      (p>0.05) increase in toxicity with the increase of exposure for trochophores and
      spermatozoa, but not for oocytes. For gametes, MET was the most toxic among the
      cryoprotectants, while PG was the most toxic for trochophores.

PMID- 15963488
TI  - In vivo cryochemotherapy of a human lung cancer model.
AB  - Cryotherapy, an efficient technique to destroy tumour cells, is sometimes applied
      locally as a palliative treatment in lung cancers. It can be performed in
      combination with chemotherapy. Our aims were to determine in vivo: (1) the
      effects of cryochemotherapy in a human lung adenocarcinoma, (2) if it presents a
      benefit compared to the separate treatments and (3) if cryotherapy allows a
      tumour retention of the drug. Cells from the A549 cell line were xenografted into
      SCID mice. Tumours were treated by cryotherapy, chemotherapy (injection of
      Vinorelbine: Navelbine) or both and were studied morphologically at variable time
      points. Apoptosis was analysed by immunohistochemical staining of cleaved caspase
      3 and by TUNEL. Intratumour Navelbine concentration was assessed by high
      performance liquid chromatography. Necrosis was important 2 h after
      cryochemotherapy (45% of the tumour surface) and at the later time points.
      Expression of cleaved caspase-3 was not significantly different from that of
      untreated tumours, except at the time point of 2 h where it was maximal (58%).
      Navelbine concentration was more important in tumours treated by chemotherapy
      than in tumours treated by cryochemotherapy, demonstrating that in our model, the
      benefit of the association observed 2h after treatment was not due to a
      concentration-dependent effect.

PMID- 15963489
TI  - A small stress protein acts synergistically with trehalose to confer desiccation
      tolerance on mammalian cells.
AB  - The ability to desiccate mammalian cells while maintaining a high degree of
      viability would be very important in many areas of biological science, including
      tissue engineering, cell transplantation, and biosensor technologies. Certain
      proteins and sugars found in animals capable of surviving desiccation might aid
      this process. We report here that human embryonic kidney (293H) cells transfected
      with the gene for the stress protein p26 from Artemia and loaded with trehalose
      showed a sharp increase in survival during air-drying. Further, we find vacuum
      drying greatly improved the ability of the cells to survive, and that the
      physical shape and structure of the cellular sample had a large influence on
      recovery following rehydration. Cells suspended in a rounded droplet survived
      desiccation markedly better than those spread as a thin film. Finally, we used
      alamarBlue to monitor cellular metabolism and Hema 3 to assess colony formation
      after vacuum-drying. AlamarBlue fluorescence indicated that the transfected 293H
      cells expressing p26 (E11'L) grew much better than the control 293H cells. In
      fact, immediate survival and colony formation in E11'L cells increased as much as
      34-fold compared with control cells when the samples were dried to a water
      content of 0.2 g H2O/g dry weight, as measured by gravimetric analysis. These
      results indicate that p26 improves cell survival following drying and
      rehydration, and suggest that dry storage of mammalian cells is a likely
      possibility in the future.

PMID- 15963490
TI  - BMP signaling and stem cell regulation.
AB  - Stem cells play an essential role in cellular specialization and pattern
      formation during embryogenesis and in tissue regeneration in adults. This is
      mainly due to a stem cell's ability to replenish itself (self-renewal) and, at
      the same time, produce differentiated progeny. Realization of these special stem
      cell features has changed the prospective of the field. However, regulation of
      stem cell self-renewal and maintenance of its potentiality require a complicated
      regulatory network of both extracellular cues and intrinsic programs.
      Understanding how signaling regulates stem cell behavior will shed light on the
      molecular mechanisms underlying stem cell self-renewal. In this review, we focus
      on comparing the progress of recent research regarding the roles of the BMP
      signaling pathway in different stem cell systems, including embryonic stem cells,
      germline stem cells, hematopoietic stem cells, and intestinal stem cells. We hope
      this comparison, together with a brief look at other signaling pathways, will
      bring a more balanced view of BMP signaling in regulation of stem cell
      properties, and further point to a general principle that self-renewal of stem
      cells may require a combination of maintenance of proliferation potential,
      inhibition of apoptosis, and blocking of differentiation.

PMID- 15963491
TI  - Exocrine pancreas development in zebrafish.
AB  - Although many of the genes that regulate development of the endocrine pancreas
      have been identified, comparatively little is known about how the exocrine
      pancreas forms. Previous studies have shown that exocrine pancreas development
      may be modeled in zebrafish. However, the timing and mechanism of acinar and
      ductal differentiation and morphogenesis have not been described. Here, we
      characterize zebrafish exocrine pancreas development in wild type and mutant
      larvae using histological, immunohistochemical and ultrastructural analyses.
      These data allow us to identify two stages of zebrafish exocrine development.
      During the first stage, the exocrine anlage forms from rostral endodermal cells.
      During the second stage, proto-differentiated progenitor cells undergo terminal
      differentiation followed by acinar gland and duct morphogenesis.
      Immunohistochemical analyses support a model in which the intrapancreatic ductal
      system develops from progenitors that join to form a contiguous network rather
      than by branching morphogenesis of the pancreatic epithelium, as described for
      mammals. Contemporaneous appearance of acinar glands and ducts in developing
      larvae and their disruption in pancreatic mutants suggest that common molecular
      pathways may regulate gland and duct morphogenesis and differentiation of their
      constituent cells. By contrast, analyses of mind bomb mutants and jagged
      morpholino-injected larvae suggest that Notch signaling principally regulates
      ductal differentiation of bipotential exocrine progenitors.

PMID- 15963492
TI  - Nicotinic receptors regulate B lymphocyte activation and immune response.
AB  - The presence of nicotinic acetylcholine receptors (nicotinic receptors) composed
      of either alpha7 or alpha4 and beta2 subunits is revealed in B lymphocytes by
      means of radioligand binding assay and Cell ELISA. Mouse B lymphocytes contained
      12,200+/-3200 of epibatidine-binding sites and 3130+/-750 of alpha-Bungarotoxin
      binding sites per cell. Mice lacking nicotinic receptor subunits alpha4, beta2 or
      alpha7 had less serum IgG and IgG-producing cells in the spleen, but showed
      stronger immune response to both protein antigen in vivo and CD40-specific
      antibody in vitro than wild-type mice. Anti-CD40-stimulated proliferation of B
      lymphocytes from beta2 knockout, but not wild-type mice was inhibited with
      nicotine. Our results indicate that signalling through nicotinic receptors
      affects both the pre-immune state and activation of B lymphocytes in the immune
      response, possibly via CD40-dependent pathway. This could contribute to immune
      depression found in tobacco smokers.

PMID- 15963493
TI  - Suppressive effects of isorhynchophylline on 5-HT2A receptor function in the
      brain: behavioural and electrophysiological studies.
AB  - Isorhynchophylline is a major oxindole alkaloid found in Uncaria species which
      have long been used in traditional Chinese medicine. Here, we investigated the
      effects of isorhynchophylline and isorhynchophylline-related alkaloids on 5
      hydroxytryptamine (5-HT) receptor-mediated behavioural responses in mice and 5-HT
      evoked current responses in Xenopus oocytes expressing 5-HT2A or 5-HT2C
      receptors. Isorhynchophylline dose-dependently inhibited 5-HT2A receptor-mediated
      head-twitch but not 5-HT1A receptor-mediated head-weaving responses evoked by 5
      methoxy-N,N-dimethyltryptamine. Pretreatment with reserpine, a monoamine
      depleting agent, enhanced the head-twitching, but did not influence the effect of
      isorhynchophylline on the behavioural response. Isocorynoxeine, an
      isorhynchophylline-related alkaloid in which the configuration of the oxindole
      moiety is the same as in isorhynchophylline, also reduced the head-twitch
      response in reserpinized mice over the same dose range as isorhynchophylline,
      while both rhynchophylline and corynoxeine, stereoisomers of isorhynchophylline
      and isocorynoxeine, did not. None of the alkaloids tested had an effect on meta
      chlorophenylpiperazine-induced hypolocomotion, a 5-HT2C receptor-mediated
      behavioural response. In experiments in vitro, isorhynchophylline and
      isocorynoxeine dose-dependently and competitively inhibited 5-HT-evoked currents
      in Xenopus oocytes expressing 5-HT2A receptors, but had less of a suppressive
      effect on those in oocytes expressing 5-HT2C receptors. These results indicate
      that isorhynchophylline and isocorynoxeine preferentially suppress 5-HT2A
      receptor function in the brain probably via a competitive antagonism at 5-HT2A
      receptor sites and that the configuration of the oxindole moiety of
      isorhynchophylline is essential for their antagonistic activity at the 5-HT2A
      receptor.

PMID- 15963494
TI  - Effect of milnacipran on extracellular monoamine concentrations in the medial
      prefrontal cortex of rats pre-treated with lithium.
AB  - Antidepressants are effective in most patients with depression, but sometimes
      have sub-optimal effects. Thus, there is a need to use more powerful
      antidepressants when dealing with treatment-resistant cases. Lithium carbonate is
      widely used for this purpose. We investigated the acute effects of milnacipran, a
      serotonin-noradrenaline reuptake inhibitor, on extracellular serotonin, dopamine
      and noradrenaline concentrations, in the rat medial prefrontal cortex. The
      effects of milnacipran were examined in rats following 7 days of treatment with
      lithium, and in untreated controls. The lithium group had significantly greater
      basal levels of extracellular serotonin than the control group. Milnacipran (3
      mg/kg) combined with lithium treatment caused a greater increase in extracellular
      noradrenaline and dopamine levels than milnacipran alone. Milnacipran (3 and 30
      mg/kg) combined with lithium treatment also caused a greater increase in
      extracellular serotonin levels than milnacipran alone. Thus, lithium might
      augment the antidepressant effects of serotonin-noradrenaline reuptake inhibitors
      by augmenting serotonin release.

PMID- 15963495
TI  - Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in
      platelets.
AB  - We examined the interplay between adenosine and the nitric oxide (NO)-containing
      oxatriazole derivative GEA 3175 in human platelets. The importance of cyclic
      guanosine 3'5'-monophosphate (cGMP)-inhibited phosphodiesterases (PDEs) was
      elucidated by treating the platelets with adenosine combined with either GEA 3175
      or the PDE3-inhibitor milrinone. The drug combinations provoked similar cyclic
      adenosine 3'5'-monophosphate (cAMP) responses. On the contrary, cGMP levels were
      increased only in GEA 3175-treated platelets. Both drug combinations reduced P
      selectin exposure, platelet adhesion and fibrinogen-binding. However, adenosine
      together with GEA 3175 was more effective in inhibiting platelet aggregation and
      ATP release. Thrombin-induced rises in cytosolic Ca2+ were suppressed by the two
      drug combinations. Adenosine administered with GEA 3175 was, however, more
      effective in reducing Ca2+ influx. In conclusion, the interaction between
      adenosine and GEA 3175 involves cGMP-mediated inhibition of PDE3. The results
      also imply that inhibition of Ca2+ influx represent another cGMP-specific
      mechanism that enhances the effect of adenosine.

PMID- 15963496
TI  - Effect of sildenafil citrate and a nitric oxide donating sildenafil derivative,
      NCX 911, on cavernosal relaxation and superoxide formation in
      hypercholesterolaemic rabbits.
AB  - Hypercholesterolaemia promotes erectile dysfunction through increased superoxide
      formation and negation of nitric oxide (NO) bioactivity in cavernosal tissue. The
      source of superoxide has not been clearly defined, however. Sildenafil (Viagra),
      the standard therapy for erectile dysfunction, may also be rendered more
      effective by the presence of an NO donor. One drug that intrinsically fulfils
      this criterion is sildenafil nitrate (NCX 911), an NO donating derivative of
      sildenafil. The objective of this study, therefore, was to determine the source
      of superoxide and its effect on erectile function in corpus cavernosum from
      hypercholesterolaemic rabbits and to determine whether NCX 911 confers an
      improvement over sildenafil citrate in this model. Hypercholesterolaemia elicited
      an increase in superoxide formation by rabbit cavernosal tissue and a reduction
      of carbachol-stimulated relaxation both of which were reversed by diphenylene
      iodonium chloride and apocynin (NADPH oxidase inhibitors). In response to sodium
      nitroprusside, hypercholesterolaemia also caused an attenuation of cavernosal
      relaxation which was not reversed with NADPH oxidase inhibitors. Both sildenafil
      citrate and NCX 911 significantly reversed impaired carbachol-stimulated
      relaxation and inhibited superoxide formation by cavernosal tissue from
      hypercholesterolaemic rabbits, NCX 911 being more potent. NCX 911 also augmented
      cavernosal cGMP levels, an effect blocked by the guanylyl cyclase inhibitor, 1H
      {1,2,4}oxadiazolo {4,3-a}quinoxalin-1-one (ODQ). These data demonstrate that
      hypercholesterolaemia promotes erectile dysfunction through an augmentation of
      superoxide derived from NADPH oxidase in cavernosal tissue. It also indicates
      that NO donating sildenafil may be therapeutically more beneficial than
      conventional sildenafil in treating erectile dysfunction with an oxidative stress
      related aetiology.

PMID- 15963497
TI  - Effect of indomethacin on E-cadherin and beta-catenin expression in HT-29 colon
      cancer cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) lower the incidence of and
      mortality from colon cancer. Although there is much evidence from epidemiological
      and laboratory studies that NSAIDs have antitumor activity and reduce the
      incidence of colon cancer, the mechanism of action remains unknown. In this
      paper, we present the effect of indomethacin on growth inhibition, induction of
      apoptosis, and alterations in the expression of several genes involved in Wnt
      signaling in HT-29 colon cancer cells. We have shown that indomethacin reduces
      the proliferation rate of HT-29 colon cancer cells and induces apoptosis.
      Concentrations of indomethacin from 10(-4) to 10(-3) M strongly inhibited the
      growth of HT-29 cells. The inhibition of growth, as well as induction of
      apoptosis was dose and time dependent. The treatment of cells with 4 x 10(-4) M
      indomethacin caused strong inhibition of cell growth (about 70%), enhanced
      expression of APC, decreased expression of beta-catenin and induced expression of
      E-cadherin proteins. Expression of beta-catenin was not markedly reduced instead,
      beta-catenin was translocated from the nucleus and cytoplasm to the plasma
      membrane. These results were confirmed by real-time RT-PCR analysis on mRNA
      level. At a concentration of 4 x 10(-4) M indomethacin there was increased
      expression of APC gene (10.9-fold induction; DeltaDeltaCt = 3.43) and E-cadherin
      gene (3.5-fold induction; DeltaDeltaCt = 1.79). These results suggest the
      antiproliferative effect of indomethacin may contribute to enhanced cell adhesion
      through increased expression of E-cadherin and translocation of beta-catenin from
      the nucleus to the cell membrane.

PMID- 15963498
TI  - Neuregulin-regulated gene expression in mammary carcinoma cells.
AB  - Recent studies have suggested that autocrine production of Neuregulin (NRG), a
      growth factor that activates members of the Epidermal Growth Factor Receptor/ErbB
      family of proto-oncogenes, is sufficient for breast tumor initiation and
      progression. To elucidate the molecular mechanisms regulating these events, we
      undertook a global analysis of genes regulated by NRG in luminal mammary
      epithelial cell lines. Gene expression profiling of estrogen receptor-positive
      T47D cells exposed to NRG-1 revealed both previously identified and novel targets
      of NRG activation. Profiling of other estrogen receptor-positive breast cancer
      cell lines, MCF7 and SUM44, yielded a group of twenty-one genes whose transcripts
      are upregulated by NRG in all three lines tested. The NRG targets are FBJ murine
      osteosarcoma viral oncogene homolog B, Early growth response 1, v-jun avian
      sarcoma virus 17 oncogene homolog, Activating transcription factor 3, Homo
      sapiens cDNA FLJ31636 fis, Jun B proto-oncogene, Forkhead box C1,
      Platelet/endothelial cell adhesion molecule 1, NADPH-dependent retinol
      dehydrogenase/reductase, Dual specificity phosphatase 5, NGF inducible protein
      TIS21, Connective tissue growth factor, Jun D proto-oncogene, Serum response
      factor, Cullin 1, v-myc avian myelocytomatosis viral oncogene, Transient receptor
      potential channel 1, Low density lipoprotein receptor, Transforming growth factor
      beta 1, Nucleoporin 88 kDa, and Pleckstrin homology-like domain A1. Since NRG
      activation of these cells induces resistance to anti-hormonal therapy, the
      identified genes may provide clues to molecular events regulating mammary tumor
      progression and hormone independence.

PMID- 15963499
TI  - Transcription factor single-minded 2 (SIM2) is ubiquitinated by the RING-IBR-RING
      type E3 ubiquitin ligases.
AB  - Human single-minded 2 (SIM2) is a member of the basic helix-loop-helix/Per-Arnt
      Sim (bHLH/PAS) family of transcription factors and is associated with the
      etiology of Down syndrome phenotype. Here, we examined a possibility of the post
      translational modification of SIM2 protein by transfecting various expression
      constructs followed by the analysis with immunoprecipitation and Western
      blotting. In fact, transient expression of SIM2 cDNA in HEK293 cells revealed
      poly-ubiquitination of SIM2 protein. In the stable transfectants, a proteasome
      inhibitor MG132 protected the poly-ubiquitinated SIM2 protein from degradation.
      Furthermore, in the cells co-transfected with SIM2 and each of four different E3
      ubiquitin ligases, SIM2 was immunoprecipitated with the RING-IBR-RING-type E3
      ubiquitin ligases, Parkin and HHARI, but it was not immunoprecipitated with other
      E3 ligases, such as one RING-type Siah-1 and the PHD type AIRE. A series of
      deletion constructs revealed that Parkin actually binds to SIM2 with the IBR (294
      377)-RING2 (378-465) domains and that the sites for poly-ubiquitination of SIM2
      reside within the PAS1-PAS2 region (aa 141-289). We postulated that transcription
      factor SIM2 and E3 ubiquitin ligase Parkin may interact each other to play an
      important physiological role in the brain development which is controlled by
      ubiquitination.

PMID- 15963500
TI  - Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1.
AB  - The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of
      cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as
      one of the key downstream signaling effectors. A critical role of mTOR signaling
      in skeletal muscle differentiation has been identified recently, and an unusual
      regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An
      mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but
      the regulatory mechanism is not completely understood. Here, we report the
      investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12
      myotube hypertrophy. Added at a later stage when rapamycin no longer had any
      effect on normal myocyte differentiation, rapamycin completely blocked myocyte
      hypertrophy as measured by myotube diameter. Importantly, a concerted increase of
      average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which
      was also inhibited by rapamycin added at a time when it no longer affected normal
      differentiation. The mTOR protein level, its catalytic activity, its
      phosphorylation on Ser2448, and the activity of S6K1 were all found increased in
      IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells
      stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic
      evidence for the requirement of mTOR and its downstream effector S6K1 in the
      regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling
      mechanisms in different stages of skeletal muscle development: While mTOR
      regulates the initial myoblast differentiation in a kinase-independent and S6K1
      independent manner, the hypertrophic function of mTOR requires its kinase
      activity and employs S6K1 as a downstream effector.

PMID- 15963501
TI  - Elevation of cyclic AMP in Jurkat T-cells provokes distinct transcriptional
      responses through the protein kinase A (PKA) and exchange protein activated by
      cyclic AMP (EPAC) pathways.
AB  - Elevating cyclic AMP with a combination of forskolin and IBMX (Fskn/IBMX) was
      found as the cause of G1 growth arrest in Jurkat T-cells, concomitant with an
      induction of the cyclin-dependent kinase inhibitor, p27Kip1. The protein kinase
      inhibitor H-89, which can discriminate between EPAC and PKA pathways, blocked the
      inhibition in cell growth and induction of p27Kip1, indicating an involvement of
      PKA, but not EPAC. The EPAC-specific cyclic AMP analogue, 8-CPT-2Me-cAMP was able
      to activate Rap1, but failed to induce growth arrest or induction p27Kip1. These
      results demonstrate that PKA, and not EPAC, mediates cyclic AMP-dependent growth
      arrest in Jurkat T-cells. To further investigate a role for EPAC in these cells,
      we carried out cDNA microarray analysis of cells stimulated with 8-CPT-2Me-cAMP.
      We identified separate groups of genes whose expression was either induced or
      repressed in response to 8-CPT-2Me-cAMP. This provides the first demonstration
      that EPAC can regulate gene expression, although it may not be involved in cell
      cycle control. Finally, we identify c-Jun as a transcription factor whose
      activity is specifically down-regulated following EPAC activation, but not PKA.
      The control of gene expression by cyclic AMP in Jurkat T-cells therefore requires
      input from the EPAC signalling cascade.

PMID- 15963502
TI  - Three-dimensional reconstruction of cells in the living lens: the relationship
      between cell length and volume.
AB  - During terminal differentiation, lens fiber cells increase in length by 100-1000
      fold. The mechanism of cellular elongation is not well understood but previous
      measurements on differentiating embryonic fiber cells indicated that cell volume
      increases in direct proportion to cell length. Fiber cells are tightly packed
      within the lens. Under these circumstances, a cellular volume increase might be
      transduced into an increase in length. Such considerations have led to the
      suggestion that volume increase may be the driving force for cell elongation. In
      the present study, we tested this model using a strain of mice in which a GFP
      transgene is expressed sporadically in the lens. We employed a combination of
      confocal microscopy, image deconvolution, and volume-rendering techniques to
      visualize the structure of individual GFP-expressing cells within the living
      lens. We examined their morphology at various stages of differentiation; from the
      central epithelium to young fiber cells. At each stage, cell length and volume
      were determined. In contrast to earlier studies, our data indicated that
      increases in cell length were not matched by a proportional increase in volume.
      Rather, the initial phase of elongation (in which cells increased in length from
      <10 to >150 microm) appeared to result largely from a change in cell shape. The
      present observations suggest that the driving force for elongation of primary and
      secondary fiber cells may differ fundamentally.

PMID- 15963503
TI  - Inhibition of neutral endopeptidase (NEP) facilitates neurogenic inflammation.
AB  - Neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) are involved
      in neuropeptide degradation and may modulate neurogenic inflammation. We
      therefore explored the effect of specific blockers of NEP and ACE on the
      intensity of neurogenic inflammation. We investigated eight subjects on three
      occasions. Two pairs of microdialysis fibers equipped with intraluminal wires
      were inserted intracutaneously into the volar forearms and electrical stimuli
      were delivered via the intraluminal electrodes. The microdialysis fibers were
      perfused either with normal saline, phosphoramidon (NEP inhibitor), or captopril
      (ACE inhibitor). CGRP release was assessed in the microdialysis eluate via a
      specific EIA and by evaluating the extent and intensity of the neurogenic flare
      via a laser Doppler imager. The area of hyperalgesia and allodynia was assessed
      during electrical stimulation. Inhibition of NEP with phosphoramidon increased
      flare intensity (P < 0.002) and size (P < 0.01), while blocking ACE had no effect
      on neurogenic vasodilation. CGRP release could be measured in microdialysis
      samples after phosphoramidon perfusion only (P < 0.03), not in samples with
      captopril or saline perfusion. No effect on the areas of hyperalgesia and
      allodynia could be detected. Our findings suggest that NEP but not ACE is most
      important for CGRP degradation in human skin. This may be of particular
      importance for the understanding of pain disorders like migraine or complex
      regional pain syndrome.

PMID- 15963504
TI  - MafA transcription factor is phosphorylated by p38 MAP kinase.
AB  - Basic-leucine zipper transcription factors of the Maf family are key regulators
      of various developmental and differentiation processes. We previously reported
      that the phosphorylation status of MafA is a critical determinant of its
      biological functions. Using Western blot and mass spectrometry analysis, we now
      show that MafA is phosphorylated by p38 MAP kinase and identify three
      phosphoacceptor sites: threonine 113 and threonine 57, evolutionarily conserved
      residues located in the transcription activating domain, and serine 272. Mutation
      of these residues severely impaired MafA biological activity. Furthermore, we
      show that p38 also phosphorylates MafB and c-Maf. Together, these findings
      suggest that the p38 MAP kinase pathway is a novel regulator of large Maf
      transcription factors.

PMID- 15963505
TI  - Phospho-STAT5 accumulation in nuclear fractions from vitamin A-deficient rat
      liver.
AB  - The growth hormone (GH)-responsive cytochrome P450 (CYP) 2C11 is down-regulated
      in vitamin A-deficient (VAD) rat liver. This study assessed the impact of a VAD
      diet on the hepatic Janus kinase-Signal Transducers and Activators of
      Transcription (JAK-STAT) system that mediates GH signalling. Nuclear tyrosine-
      and serine-phosphorylated STAT5 accumulated in VAD liver, whereas nuclear JAK2
      tyrosine kinase and SHP-1 phosphatase were decreased. Tyrosine-phosphorylated SHP
      1 was decreased to 36+/-14% of control (P<0.01), indicating its impaired
      activation in VAD liver. Episodic GH pulses increased nuclear phospho-STAT5,
      especially in control liver, but nuclear phospho-JAK2 and phospho-SHP-1 were not
      restored. CYP2C11 protein and testosterone 16alpha-hydroxylation were decreased
      in VAD liver to 67+/-16% and 76+/-19% of control, and were further decreased by
      GH to 32+/-8% and 30+/-14% of control. Thus, hypo-responsiveness of JAK-STAT in
      VAD liver is associated with impaired nuclear phospho-STAT dephosphorylation.

PMID- 15963506
TI  - Purification and functional reconstitution of the human Wilson copper ATPase,
      ATP7B.
AB  - Wilson disease is a disorder of copper metabolism, due to inherited mutations in
      the Wilson copper ATPase gene ATP7B. To purify and study the function of the
      ATPase, the enzyme was truncated by five of the six metal binding domains and
      endowed with an N-terminal histidine-tag for affinity purification. This
      construct, delta1-5WNDP, was able to functionally complement a yeast strain
      defective in its native copper ATPase CCC2. Delta1-5WNDP was purified by Ni
      affinity chromatography and reconstituted into proteoliposomes. This allowed, for
      the first time, the functional study of the Wilson ATPase in a purified,
      reconstituted system.

PMID- 15963507
TI  - The p53 pathway is synergized by p38 MAPK signaling to mediate 11,11'
      dideoxyverticillin-induced G2/M arrest.
AB  - The phytochemical 11,11'-dideoxyverticillin, derived from the fungus Shiraia
      bambusicola, has been shown to possess potent anticancer activity in vitro and in
      vivo. Here, we investigated the effect of 11,11'-dideoxyverticillin on cell cycle
      progression, and explored the potential mechanisms for this effect. A
      concentration- and time-dependent cell cycle blockade at G2/M phase was observed
      in human colon cancer cells (HCT-116) following 11,11'-dideoxyverticillin
      treatment and was associated with marked increases in levels of p53, phospho
      p53(ser20) and phospho-Chk2(Thr 68). When wild type p53 expression was
      specifically inhibited by RNA interference, HCT-116 cells treated with 11,11'
      dideoxyverticillin failed to arrest in G2/M and did not show increased phospho
      Chk2(Thr 68). On the other hand, 11,11'-dideoxyverticillin treatment also
      elicited p38 MAP kinase activity and expression of phospho-p38 MAPK. Treatment
      with a specific p38 MAPK inhibitor (SB203580) successfully inhibited p38 MAPK and
      delayed the onset of G2/M arrest induced by 0.5 microM 11,11'-dideoxyverticillin
      after approximately 6 h, but did not abolish the induction of G2/M arrest.
      Additionally, SB203580 did not alter the levels of p53, phospho-p53 (ser20), or
      phospho-Chk2 (Thr68) proteins in 11,11'-dideoxyverticillin-treated cells.
      Together, these findings indicate that p53-mediated phosphorylation of Chk2 maybe
      plays a vital role in 11,11'-dideoxyverticillin-induced G2/M arrest, and that p38
      MAPK might accelerate this progression. Our work suggests a new possibility of
      interactions among p53, Chk2 and p38 MAPK signaling in G2/M arrest.

PMID- 15963508
TI  - Occurrence of the aminoacyl-tRNA synthetases in high-molecular weight complexes
      correlates with the size of substrate amino acids.
AB  - One of the distinctive and mysterious features of mammalian aminoacyl-tRNA
      synthetases (AARSs) is the existence of stable high-molecular weight complexes
      containing 10 out of 20 AARSs. The composition and structure of these complexes
      are conserved among multicellular animals. No specific function associated with
      these structures has been found, and there is no evident rationale for a
      particular separation of AARSs in "complex-bound" and "free" forms. We have
      demonstrated a strong association between the occurrence of AARSs in the
      complexes and the volume of their substrate amino acids. The significance of this
      association is discussed in terms of the structural organization of translation
      in the living cell.

PMID- 15963509
TI  - Cry11Aa toxin from Bacillus thuringiensis binds its receptor in Aedes aegypti
      mosquito larvae through loop alpha-8 of domain II.
AB  - Bacillus thuringiensis subs israelensis produces Cry toxins active against
      mosquitoes. Receptor binding is a key determinant for specificity of Cry toxins
      composed of three domains. We found that exposed loop alpha-8 of Cry11Aa toxin,
      located in domain II, is an important epitope involved in receptor interaction.
      Synthetic peptides corresponding to exposed regions in domain II (loop alpha-8,
      beta-4 and loop 3) competed binding of Cry11Aa to membrane vesicles from Aedes
      aegypti midgut microvilli. The role of loop alpha-8 of Cry11A in receptor
      interaction was demonstrated by phage display and site-directed mutagenesis. We
      isolated a peptide-displaying phage (P5.tox), that recognizes loop alpha-8 in
      Cry11Aa, interferes interaction with the midgut receptor and attenuates toxicity
      in bioassay. Loop alpha-8 mutants affected in toxicity and receptor binding were
      characterized.

PMID- 15963510
TI  - Cyclin-dependent kinase 11(p58) interacts with HBO1 and enhances its histone
      acetyltransferase activity.
AB  - CDK11(p58), a 58kDa protein of the PITSLRE kinase family, plays an important role
      in cell cycle progression, and is closely related to cell apoptosis. To gain
      further insight into the function of CDK11(p58), we screened a human fetal liver
      cDNA library for its interacting proteins using the yeast two-hybrid system. Here
      we report that histone acetyltransferase (HAT) HBO1, a MYST family protein,
      interacts with CDK11(p58) in vitro and in vivo. CDK11(p58) and HBO1 colocalize in
      the cell nucleus. Recombinant CDK11(p58) enhances the HAT activity of HBO1
      significantly in vitro. Meanwhile, overexpression of CDK11(p58) in mammalian
      cells leads to the enhanced HAT activity of HBO1 towards free histones. Thus, we
      conclude that CDK11(p58) is a new interacting protein and a novel regulator of
      HBO1. Both of the proteins may be involved in the regulation of eukaryotic
      transcription.

PMID- 15963511
TI  - Respiratory cytochrome c oxidase can be efficiently reduced by the photosynthetic
      redox proteins cytochrome c6 and plastocyanin in cyanobacteria.
AB  - Plastocyanin and cytochrome c6 are two small soluble electron carriers located in
      the intrathylacoidal space of cyanobacteria. Although their role as electron
      shuttle between the cytochrome b6f and photosystem I complexes in the
      photosynthetic pathway is well established, their participation in the
      respiratory electron transport chain as donors to the terminal oxidase is still
      under debate. Here, we present the first time-resolved analysis showing that both
      cytochrome c6 and plastocyanin can be efficiently oxidized by the aa3 type
      cytochrome c oxidase in Nostoc sp. PCC 7119. The apparent electron transfer rate
      constants are ca. 250 and 300 s(-1) for cytochrome c6 and plastocyanin,
      respectively. These constants are 10 times higher than those obtained for the
      oxidation of horse cytochrome c by the oxidase, in spite of being a reaction
      thermodynamically more favourable.

PMID- 15963512
TI  - Tubulin cofactor A gene silencing in mammalian cells induces changes in
      microtubule cytoskeleton, cell cycle arrest and cell death.
AB  - Microtubules are polymers of alpha/beta-tubulin participating in essential cell
      functions. A multistep process involving distinct molecular chaperones and
      cofactors produces new tubulin heterodimers competent to polymerise. In vitro
      cofactor A (TBCA) interacts with beta-tubulin in a quasi-native state behaving as
      a molecular chaperone. We have used siRNA to silence TBCA expression in HeLa and
      MCF-7 mammalian cell lines. TBCA is essential for cell viability and its
      knockdown produces a decrease in the amount of soluble tubulin, modifications in
      microtubules and G1 cell cycle arrest. In MCF-7 cells, cell death was preceded by
      a change in cell shape resembling differentiation.

PMID- 15963513
TI  - Determination of hydrochlorothiazide and irbesartan in pharmaceuticals by fourth
      order UV derivative spectrophotometry.
AB  - The fourth-order derivative spectrum from the alcoholic sample is used. HCT can
      be determined by a specific peak-trough, of low intensity, at 330-340 nm. For IST
      evaluation, a peak-trough around 250-310 nm is available, common to both
      products, whose amplitude increases linearly only for low concentration values,
      while it decreases at higher values. The most difficult aspect of the analysis
      lies in how to find the optimal concentration range, so that both signals can be
      evaluated simultaneously. The best results were achieved by using a linear
      regression for HCT and a regression plane for IST.

PMID- 15963514
TI  - 2,1,3-Benzothiadiazine derivatives: synthesis and screening versus PDE4 enzyme.
AB  - A series of N-1,3 disubstituted 2,1,3-benzothiadiazine derivatives (BTDs) were
      synthesized and evaluated for their inhibitory activity versus enzymatic isoform
      PDE4 extracted from U937 cell line. Some of the tested compounds showed a high
      PDE4 inhibitory activity at 100 microM and the IC(50) value of the most
      interesting terms were evaluated. The structure-activity relationships of these
      compounds showed that the 3,5-di-tert-butyl-4-hydroxybenzyl moiety at N-1
      position is important to obtain activity at micromolar level as previously
      reported. For the same compounds the antioxidant activity were evaluated
      highlighting 14 as the most significative one. The introduction of other bulky
      substituents in N-1 position is detrimental.

PMID- 15963515
TI  - Difficulties and special issues associated with field research in behavioral
      neuroendocrinology.
AB  - Classical behavioral neuroendocrinology has focused on a limited number of
      domestic mammals and birds. The model systems used in these studies represent a
      very small proportion of the diversity of hormone-behavior interactions found in
      nature. In the last three decades, an increasing number of researchers have
      concentrated their efforts on studying behavioral neuroendocrinology of wild
      animals. Field behavioral neuroendocrinology presents a series of challenges
      ranging from the design of the experiments to sample preservation and
      transportation. The constraints of field conditions limit the number of factors
      that can be controlled for and the questions that can be addressed. On the other
      side, many behaviors can be studied only in the field, and only a few species can
      be kept in captivity. Thus, field studies are necessary to understand the
      complexity and variety of interactions between hormones, brain, and behavior. In
      this article, we will review some of the peculiarities and challenges of field
      behavioral neuroendocrinology, including solutions for some of the most commonly
      encountered technical issues.

PMID- 15963516
TI  - Rotational stability of Seidel nail distal locking mechanism.
AB  - The intramedullary distal locking mechanism in the Seidel nail uses interference
      fit, avoiding the need of a screw traversing soft tissue and the risk of
      neurovascular injury. However, there is concern for its rotational stability.
      This study was designed to test the rotational stability of the distal locking
      mechanism under the least stable conditions. A transverse osteotomy was performed
      10 cm proximal to the trochlea in 10 cadaveric humeri, followed by insertion of a
      9 mm diameter Seidel nail and distally locked. The proximal humeral segments were
      removed. Rotational test to failure was performed with a material testing
      machine. The initial medullary diameter and the amount of flange spread measured
      9.95 mm and 11.28 mm, respectively. Most of the flanges were found to be
      incompletely deployed. Failure occurred by slippage of the flanges. The average
      failure torque and torsional stiffness of the nail bone construct tested were
      0.262 N m and 0.070 N m/ degrees . The Seidel nail distal locking mechanism has
      low rotational stability on mechanical testing. However, the low failure torque
      tested in vitro does not always preclude successful fracture healing and a good
      clinical outcome. Whether the presence of rotational micro motion would be
      beneficial to bone healing would need further investigation.

PMID- 15963517
TI  - A comparison of amoxicillin and erythromycin for asymptomatic Chlamydia
      trachomatis infection in pregnancy.

PMID- 15963518
TI  - A biomechanics-based method for the quantification of muscle selectivity in a
      musculoskeletal system.
AB  - In this paper, we have developed a novel and simple method to quantify the
      ability to selectively activate our muscles in an effective pattern to achieve a
      particular task. In the context of this study, we define an effective pattern as
      that in which muscles whose mechanical contribution to the task is greatest, are
      mostly active, while the antagonist muscles are mostly silent. This new method
      uses biomechanical parameters to project the multi-channel EMGs into a three
      dimensional artificial torque space, where the EMGs are represented as muscle
      activation vectors. Using the muscle activation vectors we defined a simple
      scalar, the muscle selection index, to quantify muscle selectivity. We
      demonstrate that by using this index we are able to quantify the muscle
      selectivity during the generation of isometric shoulder or elbow torques in brain
      injured and able-bodied subjects. This method can be used during both static and
      dynamic motor tasks in a multi-articular musculoskeletal system.

PMID- 15963519
TI  - The interaction at the solid/liquid interface of 2,4-dichlorophenoxyacetic acid
      with silica modified by reaction with ammonia gas.
AB  - A method for the attachment of ammonia to modified silica gel has been developed.
      In the first step, tetraethylorthosilicate and (3
      glycidoxypropyl)trimethoxysilane were co-condensed in the presence of n
      dodecylamine, a neutral surfactant template, to produce a modified mesoporous
      silica. The epoxy group incorporated into the mesoporous silica was opened by
      ammonia gas thus introducing amine chelate groups covalently bound to the
      inorganic surface. The modified material contained 1.13+/-0.06 mmol of amine per
      gram of silica, exhibited a surface area of 831+/-29 m(2)g(-1) and a porous
      diameter of 1.95 nm. Infrared, 29Si and 13C NMR spectra were in agreement with
      the proposed structure of the modified mesoporous silica in the solid state. This
      ordered organic-inorganic hybrid presented a high capacity for the removal of the
      agrochemical 2,4-dichlorophenoxyacetic acid from water: the DeltaH and DeltaG
      values for the interaction were determined to be -110.61 and -9.37 kJ mol(-1),
      respectively.

PMID- 15963520
TI  - Rheological characterization of polysaccharide-surfactant matrices for cosmetic
      O/W emulsions.
AB  - Rheometrical techniques can be profitably used for polysaccharide matrices in
      order to evaluate their suitability for the preparation of stable cosmetic O/W
      emulsions. In particular, the rheological properties of aqueous scleroglucan
      systems were investigated under continuous and oscillatory shear conditions in a
      polymer concentration range (0.2-1.2% w/w) embracing the sol/gel transition. The
      effects due to the addition of two different surfactants (up to 10% w/w) were
      examined at constant polymer concentration (0.4% w/w). The selected additives are
      a nonionic polymeric siliconic surfactant (dimethicone copolyol) and a cationic
      surfactant (tetradecyltrimethylammonium bromide), respectively. Polysaccharide
      surfactant interactions leading to complex formation were detected also through
      rheology. The combined action of both nonionic and cationic surfactants in the
      polymer solution was examined at two different surfactant concentration levels (5
      and 10% w/w), demonstrating the beneficial effects produced on the mechanical
      properties of the polymer matrix by the coexistence of both surfactants. Such
      beneficial effects are confirmed by the stability and rheology shown by the
      emulsions prepared. In this way, the results point out the good agreement between
      the rheology of the continuous phase and the final characteristics of the
      emulsion obtained.

PMID- 15963521
TI  - Interactions of sodium montmorillonite with poly(acrylic acid).
AB  - The chemical-structural modifications of the natural clay sodium montmorillonite
      during interaction with poly(acrylic acid) were studied mainly by X-ray
      photoemission spectroscopy. Samples of modified montmorillonite were prepared
      from the reaction of sodium montmorillonite ( approximately 0.5 g) and an aqueous
      solution of poly(acrylic acid) (pH approximately 1.8, 50 g) at varying
      temperatures. X-ray diffraction indicated that the montmorillonite interlayer
      space ( approximately 13 A), formed by regular stacking of the silicate layers
      (dimension approximately 1x1000 nm), expanded to approximately 16 A as the
      reaction was carried out at room temperature and at 30 degrees C. At 60 degrees
      C, the interlayer space further expanded to approximately 20 A. The results of X
      ray photoemission spectroscopy indicated that poly(acrylic acid) molecules
      exchange sodium ions on the surface of the silicate layers. These combined
      results allowed development of a reaction model that explains the dependency of
      the interlayer expansion with temperature. Information concerning the surface
      chemical reactions and systematic increases in the interlayer distances is
      particularly useful if montmorillonite and poly(acrylic acid) are to be used for
      formation of nanocomposite materials.

PMID- 15963522
TI  - Stability and magnetic characterization of oleate-covered magnetite ferrofluids
      in different nonpolar carriers.
AB  - This work describes the preparation and stability evaluation of suspensions
      consisting of hydrophobic magnetite nanoparticles dispersed in different organic
      solvents. The ferrite particles are covered by a shell of chemisorbed oleate ions
      following a procedure that is described in detail. The oleate-covered particles
      were dispersed in different organic solvents with dielectric constants,
      epsilon(r), ranging between 1.8 and 9, and the centrifugal field strength needed
      to remove particle aggregates formed during the synthesis was determined for the
      different liquid carriers used. A thermodynamic analysis demonstrated that the
      observed stability of the suspensions in liquids with epsilon(r) < 5 is well
      correlated with the very low lyophobic attraction between the particles. This can
      easily be surmounted by thermal agitation, since the van der Waals attraction is
      negligible. In contrast, for liquids with epsilon(r) > 9, the suspensions become
      unstable because of the combined action of the van der Waals and lyophobic
      attractions, the latter being dominant for very polar solvents. Finally, a
      complete magnetic characterization of the oleate-magnetite powder, as well as of
      several stable ferrofluids prepared with it, was carried out. From this
      characterization, the magnetic diameters and magnetic moments of the particles
      immersed in the different liquid carriers were estimated and compared to those
      corresponding to the dry magnetic particles. This made it possible to estimate
      the thickness of the nonmagnetic layer on the particles.

PMID- 15963523
TI  - Zinc stable isotope fractionation during its adsorption on oxides and hydroxides.
AB  - Adsorption of Zn on goethite, hematite, birnessite, pyrolusite, corundum, and
      gibbsite was studied using a batch adsorption technique as a function of pH, zinc
      concentration in solution, and time of exposure. Adsorption from 0.01 M NaNO3
      solutions undersaturated with respect to zinc (hydr)oxide at 3<pH<8 was found to
      be reversible and equilibrium was achieved in less than 24 h. A 2pK surface
      complexation model that assumes the constant capacitance of the electric double
      layer (CCM) and postulates the formation of positively charged >MeOZn+ complexes,
      where Me=Fe, Mn, and Al, was used to describe the dependence of adsorption
      equilibria on aqueous solution composition in a wide range of pH and Zn
      concentration. The logarithms of surface stability constant for Zn interaction
      with metal oxy(hydr)oxides (>MeOH0+Zn2+-->MeOZn+) vary from -2.5 to 0.5. They are
      higher for oxy(hydr)oxides than for anhydrous oxides. Stable isotopes of zinc in
      several filtrates were measured using an ICP-MS Neptune multicollector which made
      it possible, for the first time, to assess the degree of isotopic fractionation
      between 66Zn and 64Zn during zinc adsorption on mineral surfaces. The isotopic
      offset between aqueous solution and mineral surfaces
      (Delta(66/64)Zn(soln/solid)=delta((66/64)Zn)(solution)-delta((66/64)Zn)(surface))
      was found to be weakly dependent on percentage of adsorbed metal and equals
      0.20+/-0.03, 0.17+/-0.06, -0.10+/-0.03, -0.10+/-0.09, and -0.13+/-0.12 per
      thousand for goethite, birnessite, pyrolusite, corundum, and Al(OH)3. For
      hematite, Delta(66/64)Zn varies from -0.61+/-0.10 per thousand at pH 5.5 to 
      0.02+/-0.09 per thousand at 5.8<pH<6.7. Overall, zinc stable isotopic
      fractionation induced by adsorption on most mineral surfaces does not exceed 0.2
      per thousand. We do not observe any correlation between the sign and magnitude of
      isotopic offset and the chemical nature of solid phase (hydrous versus anhydrous
      minerals), zinc surface adsorption constants (surface complexation model of the
      present work), and coordination and first-neighbor distances of surface
      >MeOZn(H2O)(n) complexes (available literature data on X-ray absorption
      spectroscopy). Apparently, the fine structure of surface complexes and the
      position and bond strength for second neighbors of zinc are likely to control its
      isotopic fractionation during adsorption on mineral surfaces. Our results
      strongly suggest that inorganic processes controlling zinc isotope adsorption on
      soil and sediment minerals should be of second-order importance compared to
      biological factors.

PMID- 15963524
TI  - Water-based latex dispersions 4. Exchange dynamics and residence times of
      nonylphenol ethoxylate in concentrated latex dispersions.
AB  - The equilibrium residence times of the nonionic surfactant nonylphenol ethoxylate
      (NP100) in a latex dispersion were determined using NMR diffusometry. At 16% w/w
      particle concentration and 0.12, 0.43 and 0.81% w/w NP100, the residence times of
      the surfactant were 0.16, 1.02 and 4.73 s in solution (tau(A)) and 0.3, 0.37 and
      0.61 s on the surface of the particles (tau(B)), respectively. At even higher
      particle concentration (>45% w/w), tau(A) and tau(B) were 1.47 and 2.2 s.
      Calculating the number of collisions that ought to result in adsorbed species, at
      16% w/w, only 2, 5 and 2 per thousand (corresponding to 0.12, 0.43 and 0.81% w/w
      NP100) resulted in adsorption, whereas at >45% w/w, only 12 per thousand resulted
      in adsorption, which suggested that the surfactant was irreversibly adsorbed on
      the particles. The small increase in collision frequency with increased particle
      concentration could be a result of a diffusion controlled adsorption, while an
      energy barrier for desorption controlled the overall exchange dynamics in the
      dispersion. The slow dynamics in the dispersion was controlled, mainly by the
      nonylphenol group, which gave NP100 a strong preference to surfaces. In addition,
      the chain length of the poly(ethylene glycol) (PEG) group changed the solution
      behavior from being that of a typical surfactant to that of a polymer.

PMID- 15963525
TI  - Relaxation phenomena of hydrolyzed polyvinylamine molecules adsorbed at the
      silica/water interface I. Saturated homogeneous polymer layers.
AB  - Surface area exclusion chromatography was used to investigate the adsorption and
      reconformation characteristics of hydrolyzed polyvinylamine molecules at
      silica/water interfaces employing radiolabeled polymers. The polymer solution was
      injected at the inlet of the column, whereas the polymer was successively
      adsorbed on the stacked glass-fiber filters constituting the stationary phase of
      the column. The filters and effluent samples collected at the outlet were
      individually analyzed for radioactivity content, which provided the adsorption
      histogram and the relative affinity of the various polymers. For saturated
      polymer layers, the relaxation process was demonstrated when the exceedingly
      adsorbed molecules desorbed. Modifications in the adsorption on the successive
      filters were thus converted into changes in the interfacial area of adsorbed
      molecules, taking into account the deviation from the plateau adsorption expected
      for nonrelaxing systems. Adsorption characteristics of nonrelaxed polymer layers
      were determined from the adsorption values determined before relaxation occurred.
      Adsorption and relaxation characteristics were determined to depend strongly on
      molecular weight and degree of hydrolysis of the polyvinylamine molecules. Half
      hydrolyzed polymers had adsorption and relaxation characteristics close to those
      of the fully hydrolyzed polyvinylamine. Accordingly, adsorption isotherms on the
      cellulose/water interface were carried out to possibly extend the main
      conclusions of the study.

PMID- 15963526
TI  - Enrichment of Pb(II) ions using phthalic acid functionalized XAD-16 resin as a
      sorbent.
AB  - A simple and reliable method has been developed using polymeric material
      containing phthalic acid as a chelating agent to concentrate ultratrace amounts
      of lead ions in aqueous solutions. After characterization by CHN, IR, and thermal
      studies, the static and dynamic sorption behavior of Pb(II) ions onto new
      synthetic resin has been investigated. The sorption has been optimized with
      respect to pH, shaking speed, and contact time between the two phases. Maximum
      sorption is achieved from solution of pH 5-8 after 10 min agitation time. The
      lowest concentration for quantitative recovery is 5.8 ng cm(-3) with a
      preconcentration factor of approximately 850. The kinetics of sorption follows
      the first-order rate equation with the rate constant k=0.58+/-0.04 min(-1). The
      variation of the equilibrium constant K(c) with temperature between 10 and 50
      degrees C yields values of DeltaH, 52.4+/-1.65 kJmol(-1), DeltaS, 186+/-5.21
      Jmol(-1)K(-1), and DeltaG(303K), -4.15+/-0.002 kJmol(-1). The sorption data of
      Pb(II) ions in the concentration range from 2.41x10(-6) to 1.44x10(-4) molL(-1)
      follows the Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherms at all
      temperatures investigated. The sorption of Pb(II) ions onto synthesized resin in
      the presence of common anions and cations has also been measured. The possible
      sorption mechanism of Pb(II) ions onto phthalic acid modified XAD-16 is also
      discussed. The sorption procedure is utilized to preconcentrate Pb(II) ions prior
      to their determination in automobile exhaust particulates by atomic absorption
      spectrometry using direct and standard addition methods.

PMID- 15963527
TI  - Differential constraints on the working memory and reading abilities of
      individuals with learning difficulties and typically developing children.
AB  - This study examined the factors that constrain the working memory span
      performance and reading ability of individuals with generalized learning
      difficulties. In the study, 50 individuals with learning difficulties (LD) and 50
      typically developing children (TD) matched for reading age completed two working
      memory span tasks. Participants also completed independent measures of the
      processing and storage operations involved in each working memory span task and
      Raven's Coloured Progressive Matrices. The results showed that despite an
      equivalent level of working memory span, the relative importance of the
      constraints on working memory differed between the groups. In addition, working
      memory span was not closely related to word recognition or sentence comprehension
      performance in the LD group. These results suggest that the working memory span
      performance of LD and TD individuals may reflect different working memory
      limitations and that individuals with generalized learning difficulties may
      approach cognitive tasks in a qualitatively different way from that of typically
      developing individuals.

PMID- 15963528
TI  - Feeding glucose or sucrose, but not trehalose, suppresses the starvation-induced
      premature pupation in the yellow-spotted longicorn beetle, Psacothea hilaris.
AB  - Under 25 degrees C and a long-day photoperiod, starvation induces premature
      pupation in 4th instar Psacothea hilaris larvae exceeding a threshold weight of
      180 mg, resulting in the formation of small but morphologically normal adults. To
      investigate possible mechanisms underlying this phenomenon, we first measured the
      hemolymph trehalose and glucose levels of starved larvae. When larvae were
      starved after 4 days of feeding (attaining the threshold weight), glucose levels
      decreased 4-fold within the next 24 h, while trehalose levels, after a temporary
      slight decrease, increased remarkably to reach a peak just before the prepupa
      stage. The effects of ingesting various nutrients on the developmental fate and
      the hemolymph sugar titers of starving larvae were then examined. Feeding on agar
      blocks containing sucrose or glucose totally suppressed the occurrence of
      premature pupation, while trehalose, fructose, casein and starch were
      ineffective. Feeding on glucose or trehalose resulted in a 6-fold decrease in
      hemolymph glucose levels and remarkably elevated trehalose levels. Since feeding
      on glucose and trehalose induced similar changes in hemolymph sugar titers but
      trehalose was not effective in suppressing premature pupation, glucose may have
      exhibited its effects via gustatory mechanisms.

PMID- 15963529
TI  - Determinants of virulence for the parasite Nosema whitei in its host Tribolium
      castaneum.
AB  - For many parasites, especially those that obligately kill the host for
      transmission, host age is crucially important to determine success. Here, we have
      experimentally investigated this relationship with the microsporidian parasite,
      Nosema whitei, in its host, the Red Flour Beetle, Tribolium castaneum. We find
      that infection is only possible in young larvae and that spore load at the time
      of transmission (i.e., host death) correlates with host body size. The data
      suggested that an infection by N. whitei prolongs the life span of the infected
      larva and prevents them from pupation. Together, virulence to the host and
      success for the parasite is mainly determined by the host age at infection. The
      patterns are consistent with theoretical predictions for obligate killer
      parasites.

PMID- 15963530
TI  - Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with
      pacing-induced heart failure.
AB  - We hypothesized that chronic xanthine oxidase inhibition (XOI) would have
      favorable effects on both ventricular and vascular performance in evolving heart
      failure (HF), thereby preserving ventricular-vascular coupling. In HF, XOI
      reduces oxidative stress and improves both vascular and myocardial function. Dogs
      were randomized to receive either allopurinol (100 mg/day p.o.) or placebo
      following surgical instrumentation for chronic measurement of left-ventricular
      pressure and dimension and during induction of HF by rapid pacing. In the placebo
      group (n = 8), HF was characterized by increased LV end-diastolic pressure
      (LVEDP, 10.2 +/- 5.5 and 29.8 +/- 3.9 mmHg, before and after HF, respectively, P
      < 0.05), end-diastolic dimension (LVEDD, from 29.5 +/- 3.2 to 34.3 +/- 3.2 mm, P
      < 0.001), and afterload (arterial elastance, Ea, from 17.9 +/- 1.2 to 42.6 +/-
      7.9 mmHg/mm, P < 0.05), and reduced contractility (End-systolic ventricular
      elastance, Ees, from 10.8 +/- 1.3 to 5.6 +/- 2.3 mmHg/mm, P < 0.05). Thus,
      ventricular-vascular coupling (Ees/Ea ratio) fell 57.6+/-9% (0.61 +/- 0.1 to 0.16
      +/- 0.1, P < 0.05). Allopurinol (n = 9) profoundly attenuated both the Ea
      increase (from 22.3 +/- 3 to 25.6 +/- 4.6 mmHg/mm, P = NS) and the fall in Ees
      (from 11.8+/-1.1 to 11.7+/-1, P = NS), thereby preserving the Ees/Ea ratio (from
      0.58 +/- 0.1 to 0.56 +/- 0.1, P < 0.001 vs. placebo). Allopurinol did not affect
      the increase in preload (LVEDP and LVEDD). XO cardiac mRNA and protein were
      similarly upregulated approximately fourfold in both groups. Allopurinol
      ameliorates increases in afterload and reductions in myocardial contractility
      during evolving HF, thereby preserving ventricular-vascular coupling. These
      results demonstrate a unique and potent hemodynamic profile of XOI, thereby
      providing further rationale for developing XOIs as a novel HF therapy.

PMID- 15963531
TI  - The search for the palmitoylethanolamide receptor.
AB  - Palmitoylethanolamide (PEA), the naturally occurring amide of ethanolamine and
      palmitic acid, is an endogenous lipid that modulates pain and inflammation.
      Although the anti-inflammatory effects of PEA were first characterized nearly 50
      years ago, the identity of the receptor mediating these actions has long remained
      elusive. We recently identified the ligand-activated transcription factor,
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as the receptor
      mediating the anti-inflammatory actions of this lipid amide. Here we outline the
      history of PEA, starting with its initial discovery in the 1950s, and discuss the
      pharmacological properties of this compound, particularly in regards to its
      ability to activate PPAR-alpha.

PMID- 15963532
TI  - Antibody against cholesteryl ester transfer protein (CETP) elicited by a
      recombinant chimeric enzyme vaccine attenuated atherosclerosis in a rabbit model.
AB  - The recombinant chimeric enzyme of AnsB-TTP-CETPC, which comprised asparagianse,
      tetanus toxin helper T-cell epitope and CETP B-cell epitope, was used to
      vaccinate New Zealand white rabbits in alum adjuvant. After anti-CETP antibodies
      were successfully produced, rabbits were fed with a high cholesterol diet for
      fifteen weeks until atherosclerotic lesions formed in arteries. The results
      showed that after CETP was inhibited by anti-CETP antibodies the fraction of
      plasma cholesterol in HDL increased and the fraction of plasma cholesterol in LDL
      decreased in rAnsB-TTP-CETPC immunized rabbits. The average size of aorta
      atherosclerotic plaques in rabbits treated with rAnsB-TTP-CETPC was 42.3% less
      than in rabbits treated with OVA (neutral control), or 47.6% less than in rabbits
      treated with rHSP 65 (negative control). The average thickness of hyperplastic
      coronary artery in rAnsB-TTP-CETPC immunized rabbits was 159+/-12 microm, which
      was significantly lower than in rHSP 65 immunized rabbits (187+/-15 microm) or
      OVA immunized rabbits (248+/-18 microm). The data reported here demonstrated that
      rAnsB-TTP-CETPC could significantly attenuate the development of atherosclerosis
      in rabbits fed with high cholesterol diet, and might be developed to an anti
      atherosclerosis vaccine in the future.

PMID- 15963533
TI  - Continuous inhibition of the renin-angiotensin system and protection from
      hypertensive end-organ damage by brief treatment with angiotensin II type 1
      receptor blocker in stroke-prone spontaneously hypertensive rats.
AB  - To investigate the short-term blockade of angiotensin II type 1 (AT1) receptor at
      the prehypertensive stage and its effects on hypertensive sequelae after
      maturation, we administered AT1 receptor blocker (ARB, 1 mg/kg/day) to male
      stroke-prone spontaneously hypertensive rats (SHRSP) from 5 to 10 weeks of age.
      Although blood pressure in the treated group was significantly lower than in the
      control group at 10 weeks of age, it gradually increased within 2-3 weeks and
      reached approximately 250 mm Hg at 17 weeks after cessation of the treatment (27
      weeks of age), and reached parity with the control after 20 weeks of age.
      Nonetheless, hypertensive end-organ damage such as cerebral lesion, cardiac
      hypertrophy and nephrosclerosis were markedly suppressed in the treated group.
      Plasma renin activity (PRA), plasma angiotensin II (AII) levels and cerebral
      angiotensin-converting enzyme (ACE) activity were also significantly lower in the
      treated group than in the control group, indicating continuous suppression of the
      circulating and local renin-angiotensin system (RAS). In the brain, intercellular
      adhesion molecule-1 (ICAM-1) mRNA expression was significantly lower in the
      cerebral cortex of the treated group than in the control group, while AT1
      receptor expression was similar. Such beneficial effects by ARB treatment were
      not found in the hydralazine-treated group, even though blood pressure changes
      were similar in both groups. These results demonstrated that early and transient
      treatment by ARB effective for the prevention of hypertensive end-organ damage.
      This may be due to the low concentration of plasma angiotensin II by continuous
      inhibition of RAS even after maturation.

PMID- 15963534
TI  - General methodology for nonlinear modeling of neural systems with Poisson point
      process inputs.
AB  - This paper presents a general methodological framework for the practical modeling
      of neural systems with point-process inputs (sequences of action potentials or,
      more broadly, identical events) based on the Volterra and Wiener theories of
      functional expansions and system identification. The paper clarifies the
      distinctions between Volterra and Wiener kernels obtained from Poisson point
      process inputs. It shows that only the Wiener kernels can be estimated via cross
      correlation, but must be defined as zero along the diagonals. The Volterra
      kernels can be estimated far more accurately (and from shorter data-records) by
      use of the Laguerre expansion technique adapted to point-process inputs, and they
      are independent of the mean rate of stimulation (unlike their P-W counterparts
      that depend on it). The Volterra kernels can also be estimated for broadband
      point-process inputs that are not Poisson. Useful applications of this modeling
      approach include cases where we seek to determine (model) the transfer
      characteristics between one neuronal axon (a point-process 'input') and another
      axon (a point-process 'output') or some other measure of neuronal activity (a
      continuous 'output', such as population activity) with which a causal link
      exists.

PMID- 15963535
TI  - Lifesaving explains mortality decline with time.
AB  - Mortality rates of human populations in developed countries are declining with
      time. We show that this effect can be explained via a 'lifesaving' methodology.
      Our approach is based on considering a non-homogeneous Poisson process of
      potentially harmful events. Each of these events can be 'cured' with a given
      probability or can result in a termination of the Poisson process (death) with a
      complementary probability. A lifesaving ratio, defining the corresponding
      relative increase in life expectancy for homogeneous and heterogeneous
      populations is analyzed. Some generalizations are discussed. Several simple
      examples are considered.

PMID- 15963536
TI  - SKY and FISH analysis of radiation-induced chromosome aberrations: a comparison
      of whole and partial genome analysis.
AB  - For a retrospective dose estimation of human exposure to ionising radiation, a
      partial genome analysis is routinely used to quantify radiation-induced
      chromosome aberrations. For this purpose, fluorescence in situ hybridisation
      (FISH) with whole chromosome painting probes for selected chromosomes is usually
      applied covering about 20% of the whole genome. Since genome-wide screening
      techniques like spectral karyotyping (SKY) and multiplex FISH (mFISH) have been
      developed the detection of radiation-induced aberrations within the whole genome
      has now become feasible. To determine the correspondence between partial and
      whole genome analysis of radiation-induced chromosome aberrations, they were
      measured comprehensively in this study using in vitro irradiated blood samples
      from three donors. We were able to demonstrate that comparable results can be
      detected with both approaches. However, complex aberrations might be
      misinterpreted by partial genome analysis. We therefore conclude that whole
      genome analysis by SKY is useful especially in the high dose range to correct
      aberration data for complex exchange aberrations.

PMID- 15963537
TI  - The lateral septal area is involved in the pressor pathway activated by
      microinjection of norepinephrine into the rat brain cingulate cortex.
AB  - The cingulate cortex (CC) is involved in cardiovascular regulation.
      Microinjection of norepinephrine (NE) into the Cg3 area of the CC caused
      vasopressin release and pressor responses in unanesthetized rats. Microinjection
      of acetylcholine (ACh) into the lateral septal area (LSA) of unanesthetized rats
      caused similar vasopressin-related pressor responses. The LSA is anatomically
      connected to the CC and the paraventricular nucleus (PVN) of the hypothalamus, an
      important nucleus involved in vasopressin synthesis. Therefore, we attempted to
      verify if the cholinergic neurotransmission within the LSA is involved in the
      mediation of the pressor response to the microinjection of NE into the Cg3. Local
      pretreatment with lidocaine, muscimol, atropine or hemicholinium-3 microinjected
      into the LSA blocked the pressor response to the microinjection of NE injection
      into the Cg3. Conversely, pretreatment with physostigmine microinjected into the
      LSA potentiated the pressor response to NE injection into the Cg3. The present
      results indicate that the synapses in the LSA are part of the pressor pathway
      originating at the CC and that cholinergic neurotransmission within the LSA is
      involved in the mediation of the cardiovascular responses to the microinjection
      of NE into the Cg3.

PMID- 15963538
TI  - The dopamine D3 receptor and drug dependence: effects on reward or beyond?
AB  - Abused drugs (alcohol, heroin, cocaine, tetrahydrocannabinol and nicotine) elicit
      a variety of chronically relapsing disorders by interacting with brain reward
      systems. All of these drugs increase dopamine levels in the shell of nucleus
      accumbens, a structure that has been involved in their hedonic and reinforcing
      properties. Dopamine D(3) receptors (DRD3) are predominantly expressed in the
      nucleus accumbens, but also in the ventral tegmental area and in the amygdala,
      brain structures implicated in drug dependence. Moreover, converging
      pharmacological, human post-mortem and genetic studies have suggested the
      involvement of the DRD3 in drug dependence. Based on early studies using non
      selective DRD3 ligands, the DRD3 was proposed as having a direct role in the
      rewarding effects of psychostimulants. However, recent studies using highly
      selective DRD3 ligands and the DRD3-deficient mice have revealed that the DRD3 is
      not implicated in the direct reinforcing effects of drugs of abuse. In contrast,
      the DRD3 appears to be implicated in the motivation to self-administer drugs
      under schedules where the response requirements are high. This is consistent with
      a behavioral economic analysis, with the effects of DRD3 ligands revealed only in
      situations with high prices for drug. Drug-self administration and relapse are
      strongly controlled by environmental stimuli. The DRD3 strongly modulates the
      influence of these environmental stimuli on drug-seeking behavior. DRD3 blockade
      disrupts the reactivity to drug-associated stimuli in various paradigms, such as
      second-order schedules of drug-self administration, conditioned place preference
      and Pavlovian conditioning procedures. In several paradigms, the involvement of
      the DRD3 has been confirmed by using DRD3-deficient mice. On the contrary,
      reactivity to stimuli associated with natural reinforcers, such as food, appears
      unaffected by modulation of the DRD3. All these findings suggest that DRD3
      ligands may represent a useful strategy for decreasing relapse in abstinent drug
      abusers.

PMID- 15963539
TI  - Ambient temperature related sleep changes in rats neonatally treated with
      capsaicin.
AB  - Ambient temperature related sleep changes in rats neonatally treated with
      capsaicin. PHYSIOL BEHAV 00(0) 000-000, 2004. The study was conducted on adult
      male Wistar rats, neonatally treated with capsaicin to destroy the peripheral
      warm receptors. The sleep-wakefulness was recorded for 5 h at an ambient
      temperature (T(amb)) of 18, 24, 30 and 33 degrees C on different days. The rectal
      temperatures (T(r)) of the rats were studied on exposure to 6 and 37 degrees C
      for 2 h to assess their thermoregulatory ability. The changes in the behavioral
      thermoregulation were assessed by noting the thermal preference of rats when they
      were placed in an environmental chamber with 3 interconnected compartments
      maintained at 24, 27 and 30 degrees C. Slow wave (SWS) and rapid eye movement
      (REM) sleep were decreased at 18 degrees C and increased at 30 degrees C, in
      control rats. There was a decrease in REM sleep and no change in SWS when T(amb)
      was raised from 30 to 33 degrees C. However, in neonatally capsaicin treated
      rats, sleep was increased even at 33 degrees C, though there was no significant
      change in sleep when T(amb) was increased from 18 to 24 degrees C. Capsaicin
      treated rats showed thermoregulatory deficiency at 37 degrees C but the thermal
      preference was unaltered in these rats. The results suggest that the central warm
      receptors can produce alteration in sleep at different T(amb), even in absence of
      peripheral warm receptors. The behavioral thermoregulation was unaffected in
      these rats, though their ability to defend the body temperature in warm
      environment was affected.

PMID- 15963540
TI  - Silicon-mediated alleviation of Mn toxicity in Cucumis sativus in relation to
      activities of superoxide dismutase and ascorbate peroxidase.
AB  - The effects of exogenous silicon (Si) on plant growth, activities of superoxide
      dismutase (SOD), guaiacol peroxidase (GPX), ascorbate peroxidase (APX),
      dehydroascorbate reductase (DHAR), glutathione reductase (GR) and catalase, and
      concentrations of ascorbate and glutathione were investigated in cucumber
      (Cucumis sativus L.) plants treated with excess manganese (Mn) (600 microM).
      Compared with the treatment of normal Mn (10 microM), excess Mn significantly
      increased H2O2 concentration and lipid peroxidation indicated by accumulation of
      thiobarbituric acid reactive substances. The leaves showed apparent symptoms of
      Mn toxicity and the plant growth was significantly inhibited by excess Mn. The
      addition of Si significantly decreased lipid peroxidation caused by excess Mn,
      inhibited the appearance of Mn toxicity symptoms, and improved plant growth. This
      alleviation of Mn toxicity by Si was related to a significant increase in the
      activities of SOD, APX, DHAR and GR and the concentrations of ascorbate and
      glutathione.

PMID- 15963541
TI  - Flavonoids, triterpenoids and a lignan from Vitex altissima.
AB  - A new tetrahydrofuranoid lignan, altissinone (1) and a new acylated flavone C
      glucoside, 2''-O-p-hydroxybenzoylorientin (2), were isolated in addition to
      several known triterpene acids and flavonoids from the ethyl acetate extractives
      of the leaves of Vitex altissima. The structures of the compounds were
      established based on interpretation of high resolution NMR (HMQC, HMBC and NOESY)
      spectral data. The ethyl acetate extract exhibited significant anti-inflammatory
      activity in rat paw edema model. The flavonoids and triterpene acids showed
      moderate antioxidant and 5-lipoxygenase enzyme inhibitory activities,
      respectively.

PMID- 15963542
TI  - Chickpea wilt: identification and toxicity of 8-O-methyl-fusarubin from Fusarium
      acutatum.
AB  - Fusarium acutatum was isolated from wilting chickpea plants in Pakistan.
      Filtrates from cultures grown on a defined liquid medium caused permanent wilting
      of chickpea cuttings and killed cells, isolated enzymically from healthy plants,
      in a bioassay. Toxic activity was retained by a cyano solid phase extraction
      cartridge and the toxin was isolated by elution from the cartridge in
      acetonitrile and Si-gel thin layer chromatography of the eluate. Analytical HPLC
      of the compound on a cyano column with diode array detection gave a single peak
      with a homogeneous spectrum and lambda(max) at 224 and 281 nm. NMR and mass
      spectral studies showed that the toxin was 8-O-methyl-fusarubin. The pure
      compound caused permanent wilting of chickpea cuttings and the LD50 value in the
      cell bioassay was 327 ng/ml.

PMID- 15963543
TI  - Pyrrolizidine alkaloids from Anchusa strigosa and their antifeedant activity.
AB  - The pyrrolizidine alkaloid (PA) content of flowers, leaves, and roots of Anchusa
      strigosa (Boraginaceae) was analysed by ESI-LC-MS. Six PAs, including two new
      natural compounds, were detected, characterized by NMR spectroscopy, and
      quantified in each plant organ. The results indicated that the highest total
      concentration of PAs was in the leaves (23.63 mg/g of dried part), followed by
      the flowers (19.77 mg/g), and finally by the roots (1.80 mg/g). All PAs isolated
      were subjected to Spodoptera exigua and Pieris brassicae larvae. Feeding activity
      by both herbivore species using a bioassay was inhibited up to circa 75%
      depending on PA and applied concentration.

PMID- 15963544
TI  - A simple colorimetric method to detect biological evidence of human exposure to
      microcystins.
AB  - Toxic cyanobacteria are contaminants of surface waters worldwide. Microcystins
      are some of the most commonly detected cyanotoxins. Biological evidence of human
      exposure may be difficult to obtain due to limitations associated with cost,
      laboratory capacity, analytic support, and expertise. We investigated the
      application of an enzyme-linked immunosorbant assay (ELISA) to detect
      microcystins in human serum. We analyzed ten serum samples collected from
      dialysis patients who were known to be exposed to a mixture of microcystins
      during a 1996 outbreak in Brazil. We applied a commercially available ELISA
      method to detect microcystins in serum, and we compared the ELISA results to a
      more specific method, liquid chromatography/mass spectrometry (LC/MS) that was
      also used to detect microcystins in serum. The Spearman correlation coefficient
      was calculated using serum microcystin concentrations in split samples obtained
      by the two methods. Serum microcystin concentrations were similar, and we found
      good correlation of microcystin concentrations between the two methods. The ELISA
      detected total microcystins, median=19.9 ng/ml; LC/MS detected microcystin-LR
      equivalents, median=21.2 ng/ml; Spearman r=0.96, p<0.0001. We found that ELISA is
      a simple, accessible method to screen human serum for evidence of microcystin
      exposure.

PMID- 15963545
TI  - Mutational analysis of the RNA-binding domain of the Prunus necrotic ringspot
      virus (PNRSV) movement protein reveals its requirement for cell-to-cell movement.
AB  - The movement protein (MP) of Prunus necrotic ringspot virus (PNRSV) is required
      for cell-to-cell movement. MP subcellular localization studies using a GFP fusion
      protein revealed highly punctate structures between neighboring cells, believed
      to represent plasmodesmata. Deletion of the RNA-binding domain (RBD) of PNRSV MP
      abolishes the cell-to-cell movement. A mutational analysis on this RBD was
      performed in order to identify in vivo the features that govern viral transport.
      Loss of positive charges prevented the cell-to-cell movement even though all
      mutants showed a similar accumulation level in protoplasts to those observed with
      the wild-type (wt) MP. Synthetic peptides representing the mutants and wild-type
      RBDs were used to study RNA-binding affinities by EMSA assays being approximately
      20-fold lower in the mutants. Circular dichroism analyses revealed that the
      secondary structure of the peptides was not significantly affected by mutations.
      The involvement of the affinity changes between the viral RNA and the MP in the
      viral cell-to-cell movement is discussed.

PMID- 15963546
TI  - Human immunodeficiency virus type 1 KK26-27 matrix mutants display impaired
      infectivity, circularization and integration but not nuclear import.
AB  - We analyzed the role of human immunodeficiency virus (HIV)-1 matrix protein (MA)
      during the virus replication afferent phase. Single-round infection of H9 T
      lymphocytes showed that the combined mutation of MA Lys residues 26-27 in MA
      reported nuclear localization signal (NLS)-1 impaired infectivity, abrogated 2
      LTR-circle formation and significantly reduced integration. However, the mutation
      did not affect viral DNA docking to chromatin in either interphasic or mitotic
      cells, indicating that MA N-terminal basic domain should not represent a major
      determinant of HIV-1 nuclear import in T lymphocytes. These data point to a
      previously unreported role of MA in the late, post-chromatin-binding, afferent
      phase of HIV-1 replication cycle.

PMID- 15963547
TI  - A new sensitive and quantitative HTLV-I-mediated cell fusion assay in T cells.
AB  - Similar to several other viruses, human T cell leukemia virus type I (HTLV-I)
      induces the formation of multinucleated giant cells (also known as syncytium)
      when amplified in tissue culture. These syncytia result from the fusion of
      infected cells with uninfected cells. Due to the intrinsic difficulty of
      infecting cells with cell-free HTLV-I virions, syncytium formation has become an
      important tool in the study of HTLV-I infection and transmission. Since most HTLV
      I-based cell fusion assays rely on the use of non-T cells, the aim of this study
      was to optimize a new HTLV-I-induced cell fusion assay in which HTLV-I-infected T
      cell lines are co-cultured with T cells that have been transfected with an HTLV-I
      long terminal repeat (LTR) luciferase reporter construct. We demonstrate that co
      culture of various HTLV-I-infected T cells with different transfected T cell
      lines resulted in induction of luciferase activity. Cell-to-cell contact and
      expression of the viral gp46 envelope protein was crucial for this induction
      while other cell surface proteins (including HSC70) did not have a significant
      effect. This quantitative assay was shown to be very sensitive. In this assay,
      the cell fusion-mediated activation of NF-kappaB and the HTLV-I LTR occurred
      through previously described Tax-dependent signaling pathways. This assay also
      showed that cell fusion could activate Tax-inducible cellular promoters. These
      results thus demonstrate that this new quantitative HTLV-I-dependent cell fusion
      assay is versatile, highly sensitive, and can provide an important tool to
      investigate cellular promoter activation and intrinsic signaling cascades that
      modulate cellular gene expression.

PMID- 15963548
TI  - Differential expression of LFA-3, Fas and MHC Class I on Ad5- and Ad12
      transformed human cells and their susceptibility to lymphokine-activated killer
      (LAK) cells.
AB  - Adenovirus (Ad) E1A is a potent oncogene and has been shown to deregulate the
      expression of a large number of cellular genes leading to cellular
      transformation. Here we have analysed the expression of several immunomodulatory
      molecules on the surface of a set of human cell lines transformed with either
      Ad12 or Ad5. Human cells transformed with Ad12 demonstrated reduced expression of
      cell surface LFA-3, Fas and MHC class I when compared to Ad5-transformed cells.
      Furthermore, Ad12-transformed human cell lines demonstrated greater
      susceptibility to lysis by lymphokine-activated killer (LAK) cells, compared to
      Ad5-transformed human cell lines. In contrast, previous studies with rodent cells
      showed that both Ad5- and Ad12-transformed rat cells were susceptible to LAK
      cells. Thus, transformation of human cells with Ad5 or Ad12 results in
      differences in the expression of immunomodulatory molecules on the cell surface
      and differential recognition of these virus-transformed cells by immune effector
      cells.

PMID- 15963549
TI  - Parametric decomposition of optic flow by humans.
AB  - Ego motion and natural motions in the world generate complex optic flows in the
      retina. These optic flows, if produced by rigid surface patches, can be
      decomposed into four components, including rotation and expansion. We showed
      previously that humans can precisely estimate parameters of these components,
      such as the angular velocity of a rotational motion and the rate of expansion of
      a radial motion. However, natural optic flows mostly display motions containing a
      combination of more than one of these components. Here, we report that when a
      pure motion (e.g., rotation) is combined with its orthogonal component (e.g.,
      expansion), no bias is found in the estimate of the component parameters. This
      suggests that the visual system can decompose complex motions. However, this
      decomposition is such that the presence of the orthogonal component increases the
      discrimination threshold for the original component. We propose a model for how
      the brain decomposes the optic flow into its elementary components. The model
      accounts for how errors in the estimate of local-velocity vectors affect the
      decomposition, producing the increase of discrimination thresholds.

PMID- 15963550
TI  - Development of a Ct equation taking into consideration the effect of lot
      variability on the inactivation of Cryptosporidium parvum oocysts with ozone.
AB  - Cryptosporidium parvum oocysts are prevalent in surface water and ground water
      under the influence of surface water, and are difficult to inactivate using free
      chlorine, the most common disinfectant currently used for treating drinking
      water. In contrast, it has been shown that ozone is a more effective disinfectant
      than chlorine. US EPA is currently evaluating a treatment rule, which addresses
      the control of C. parvum oocysts in drinking water. The use of Ct (average
      disinfectant concentration multiplied by characteristic contact time) values is
      being considered as one of the options for demonstrating adequate control of this
      microbial contaminant. The purpose of this study is to incorporate the
      variability in inactivation kinetics among different lots of oocysts and to
      develop a statistical model for Ct based on first-order delayed Chick--Watson
      inactivation kinetics. A Bayesian approach is used to estimate the delayed Chick-
      Watson kinetic parameters. A log-linear regression analysis is then used to
      represent the effect of temperature on the resulting kinetic parameters. The
      overall model developed in this study provides an approach for water utilities
      and regulatory agencies to decide on the level of safety needed when developing
      treatment requirements for the inactivation of C. parvum oocysts with ozone as
      part of broader risk assessment considerations.

PMID- 15963551
TI  - Assessment of insecticide contamination in runoff and stream water of small
      agricultural streams in the main soybean area of Argentina.
AB  - The first- and second-order streams, Brown and Horqueta, respectively, which are
      located in the main area of soybean production in Argentina were examined for
      insecticide contamination caused by runoff from nearby soybean fields. The
      insecticides most widely used in Argentina (chlorpyrifos, cypermethrin and
      endosulfan) were detected in sediments, suspended particles and water. Highest
      concentrations in suspended particles were 318 microg/kg for endosulfan in the
      stream Horqueta, while 226 microg/kg chlorpyrifos and 13.2 microg/kg cypermethrin
      were measured in the stream Brown. In the Horqueta stream 150 and 53 microg/kg
      chlorpyrifos and cypermethrin were detected in runoff sediments, respectively.
      Whereas cypermethrin concentrations in the suspended particles were relatively
      low, levels in the floodwater of Brown reached 0.7 microg/l. The highest
      chlorpyrifos concentration in floodwater was 0.45 microg/l in Brown. However,
      endosulfan was not detected in the water phase. In runoff water the highest
      concentrations measured were 0.3 microg/l for chlorpyrifos in Horqueta and 0.49
      microg/l for cypermethrin in the Brown stream. On five sampling dates during the
      pesticide application period in Brown stream (2002/2003) the concentration of
      chlorpyrifos and cypermethrin in runoff and/or floodwater exceeded the water
      quality criteria for freshwater mentioned in this study. In three cases this
      insecticide concentration was measured in stream water, indicating an acute risk
      to aquatic life. The acute toxicity-exposure-ratio (TER) for chlorpyrifos and
      cypermethrin also shows an acute risk for aquatic invertebrates in the Brown
      stream. In the Horqueta chlorpyrifos concentrations in the runoff exceeded the
      safety levels three times during the application period (2001/2002), potentially
      endangering the aquatic fauna. Effects on aquatic macroinvertebrates after
      insecticide contamination were reported in earlier studies in Horqueta stream.

PMID- 15963552
TI  - How accurately do semi-permeable membrane devices measure the bioavailability of
      polycyclic aromatic hydrocarbons to Daphnia magna?
AB  - Semi-permeable membrane devices (SPMDs) are passive samplers that have been
      designed to sample the bioavailable fractions of hydrophobic organic compounds in
      aquatic ecosystems. This study aims at evaluating the ability for SPMD to sample
      polycyclic aromatic hydrocarbons (fluoranthene, pyrene and benzo[a]pyrene) that
      are actually bioavailable to Daphnia magna. For that purpose, the SPMD-available
      fraction and the bioavailable fraction to D. magna are compared in controlled
      media with Dissolved Organic Matters (DOMs) from various origins and at different
      concentrations. The presence of all but one DOM reduces the accumulation of PAHs
      in SPMD or in D. magna. Moreover, this comparative laboratory study shows that in
      10 cases on 13, the SPMD-available fraction is close to the available fraction to
      D. magna. When significant differences are observed between SPMD-available and
      bioavailable fractions, they remain less than 50% at DOM concentrations below
      10mg/l DOC, which corresponds to a maximum DOC concentration usually found in
      temperate rivers. This study confirms the suitability of the SPMD technique to
      monitor readily bioavailable hydrophobic contaminants in aquatic environments
      containing DOM from various origins and characteristics.

PMID- 15963553
TI  - Subsoil TPH and other petroleum fractions-contamination levels in an oil storage
      and distribution station in north-central Mexico.
AB  - Many oil industry related sites have become contaminated due to the activities
      characteristic of this industry, such as oil exploration and production,
      refining, and petro-chemistry. In Mexico, reported hydrocarbon spills for the
      year 2000 amounted to 185203, equivalent to 6252 tons (PEMEX, 2000). The first
      step for the remediation of these polluted sites is to assess the size and
      intensity of the oil contamination affecting the subsoil and groundwater,
      followed by a health risk assessment to establish clean up levels. The aim of
      this work was to characterize the soil and water in a north-central Mexico Oil
      Storage and Distribution Station (ODSS), in terms of TPHs, gasoline and diesel
      fractions, BTEX, PAHs, MTBE, and some metals. Besides, measurements of the
      explosivity index along the ODSS were made and we describe and discuss the risk
      health assessment analysis performed at the ODSS, as well as the recommendations
      arising from it. Considering soils with TPH concentrations higher than 2000 mg
      kg(-1), the contaminated areas corresponding to the railway zone is about 12776.5
      m2, to the south of the storage tanks is about 6558 m2, and to the south of the
      filling tanks is about 783 m2. Total area to be treated is about 20107 m2 (volume
      of 20107 m3), considering 1m depth.

PMID- 15963554
TI  - A case of endometrial stromal sarcoma with curvilinear calcification.
AB  - BACKGROUND: Although many histopathological, clinical, and imaging findings of
      ESS have been described, intense calcifications have not been reported
      previously. CASE: A 54-year-old female was admitted with vaginal bleeding and
      abdominal pain. Gynecologic examination revealed a huge, firm pelvic mass
      extending up to the epigastrium. Transabdominal ultrasonography and computed
      tomography demonstrated a well-demarcated uterine mass containing heterogeneous
      solid and cystic areas and a centric curvilinear calcification. Histopathological
      diagnosis was established as undifferentiated high-grade endometrial stromal
      sarcoma. CONCLUSION: Endometrial stromal sarcomas should be considered in the
      differential diagnosis of uterine masses containing curvilinear calcifications.

PMID- 15963555
TI  - Meigs syndrome and gliomatosis peritonei: a case report and review of literature.
AB  - To the best of our knowledge, pseudo-Meigs syndrome (PMS) has never been
      described in the setting of gliomatosis peritonei (GP), both arising from an
      ovarian teratoma. We present a case of ovarian teratoma with both these rare
      findings. The case is unique as it presents two rare manifestations of ovarian
      teratoma in the same patient; there are many cases in the literature where both
      these manifestations have been described in different patients. The case is also
      rare because lymph node involvement along with gliomatosis was found. We review
      the literature for these two rare complications of ovarian teratoma.

PMID- 15963556
TI  - Is the I-131 whole-body scanning proper for follow-up management of the patients
      with malignant struma ovarii without performing the thyroidectomy?

PMID- 15963557
TI  - Comparison of reproductive performance by artificial insemination versus natural
      service sires in California dairies.
AB  - This study compared the calving to conception intervals for cows in AI pens with
      cows exposed to natural service sires, controlling for milk production, mastitis
      occurrence, parity and calving month effects. Records from 10 western United
      States dairy herds (mean herd size = 2058 cows) were evaluated retrospectively
      over an 18-month period. Eight bull breeding analysis cohorts were created (the
      first cohort 0-50 days in milk and the remaining cohorts at 25 days in milk
      intervals through 226 days). The cohorts contained non-pregnant cows that were
      first moved into bullpens during the described cohort period. Equal numbers of
      non-pregnant cows only exposed to AI during the cohort period were randomly
      selected from the pool of eligible non-pregnant cows. An AI cow was used only
      once in the data analysis, but was included in a bull breeding cohort at a later
      date if she remained non-pregnant and was transferred to a bullpen. Univariate
      and multivariate survival analysis was used to compare the calving to conception
      intervals. Cows in AI groups had higher hazard rates for pregnancy across all
      cohorts. Parity and milk production were significantly associated with risk for
      pregnancy. In herds that practice a mixture of AI and bull breeding, overall herd
      reproductive performance might be improved by allowing cows more opportunities at
      AI prior to moving them into clean-up bullpens.

PMID- 15963558
TI  - Cost comparison of natural service sires and artificial insemination for dairy
      cattle reproductive management.
AB  - Despite the widespread popularity of artificial insemination, many dairymen still
      prefer the use of natural service sires due to a variety of reasons, including a
      common perception that it is easier to manage and less expensive than AI. Little
      has been done to estimate the explicit and implicit costs, including the probable
      loss of genetic progress associated with the use of natural service sires in
      dairy herds. A partial budget approach was used to stochastically model the
      expected costs and returns of reproductive management options in large, western,
      Holstein dairies. Option one was natural service sires managed using currently
      recommended approaches including breeding soundness evaluations, bull
      vaccination, and a rotational breeding system. Option two was an AI system using
      a modified Presync-Ovsynch timed AI program in conjunction with estrus detection
      and inseminations performed by a commercial route breeder. Stochastic variables
      in the model included the cost of the lactating ration and purchased bulls, as
      well as the value received for milk, market bulls, and net merit gains. All other
      variables were treated deterministically. Under the model's assumptions, the use
      of natural service sires averaged approximately US dollar 10 more in cost per cow
      per year as compared to an AI program. Sixty percent of the time, AI was less
      expensive than using bulls. However, there was wide variation in expected
      differences in cost between the two systems with net merit estimates having the
      largest impact, followed by prices received for milk sold and market bulls.

PMID- 15963559
TI  - The effects of vetrabutin chlorhydrate and oxytocin on stillbirth rate and
      asphyxia in swine.
AB  - Oxytocin and vetrabutin chlorhydrate (VC) are used to reduce the duration of
      farrowing in swine. The objective of the present study was to evaluate the use of
      these products on intra-partum stillbirth (IPS) rate and asphyxia. At the onset
      of parturition, sows (n=180) were allocated to receive 2 mL of saline (control
      group), oxytocin (40 IU i.m.) or 100mg of VC per 60 kg of body weight, with all
      treatments given i.m. Oytocin-treated sows had a higher number of IPS than the VC
      and Control groups (means, 1.2, 0.8 and 0.6, respectively; P<0.001), and the
      highest percentage of ruptured umbilical cords (76.0, 9.4 and 37.5%; P<0.003).
      There were differences among groups for duration of farrowing (means, 163.0,
      211.2 and 306.9 min in the oxytocin, VC and control groups; P<0.001), interval
      between piglets (13.9, 19.2 and 28.1 min; P<0.001), and in IPS, the incidence of
      ruptured umbilical cords was 76.0, 9.4 and 37.5% (P<0.003) and absence of a fetal
      heartbeat was 53.3, 16.9 and 12.5% (P<0.05). Although oxytocin decreased both
      duration of farrowing and interval between piglets by approximately 50% relative
      to control sows, it resulted in a significantly higher rate of IPS, in
      association with a much higher incidence of ruptured umbilical cord and absence
      of a fetal heartbeat. Treatment with VC reduced farrowing duration by
      approximately 1.5h, with an IPS rate that was not significantly different from
      controls but significantly lower than that of oxytocin-treated sows.

PMID- 15963560
TI  - Transcervical artificial insemination in the cat.
AB  - Many studies have reported new reproductive techniques for reproduction in
      endangered non-domestic felids. Artificial insemination is an important tool for
      developing breeding programs. This manuscript reviews recent progress in feline
      artificial insemination, with particular emphasis on intrauterine sperm
      deposition. Intrauterine insemination of felids results in higher fertilization
      rates than intravaginal insemination, despite insemination with fewer sperm.
      Although surgical insemination was utilized historically, there are some reports
      of catheterization of the cervix of the queen. Recently, a new technique and
      catheter were proposed for transcervical insemination of fresh or frozen-thawed
      semen.

PMID- 15963561
TI  - Event-related brain potentials elicited during word recognition by adult good and
      poor phonological decoders.
AB  - Cognitive processing of lexical and sub-lexical stimuli was compared for good and
      poor adult phonological decoders. Sixteen good decoders and 16 poor decoders,
      average age 19 years, silently read 150 randomly computer presented sentences
      ending in incongruous regular, irregular, or nonwords and 100 congruent filler
      sentences. Electro-encephalographic recordings were made from the final word of
      each incongruous sentence. Although no significant group differences were found,
      good decoders showed specialised hemispheric word recognition processing at P200
      and P300. Nonwords elicited greater N200 and P300 amplitudes for both good and
      poor decoders. Larger amplitude P200s were elicited by poor decoders when
      processing nonwords. These findings provide evidence for separable lexical and
      sub-lexical procedures and support a psychophysiological basis for a core
      phonological deficit in poor phonological decoders.

PMID- 15963562
TI  - Inlay shading effect on the photopolymerization kinetic of a dental composite
      material used as bonding system in an indirect restoration technique.
AB  - OBJECTIVES: To define the inlay shading effect on the polymerization levels and
      kinetics of a light activated bonding system for an indirect restoration
      technique. MATERIALS AND METHODS: For the bonding system, an adhesive: Excite
      (Ivoclar-vivadent) and a composite: Z250 (3M-ESPE, St Paul Minnesota, USA) were
      investigated. A Demetron (Kerr USA) light curing unit was used. The composite
      inlay blocks of 2 mm thick were used for the experiment (Artglass A2 Heraeus,
      Kulzer, Dormagen, Germany). The bonding composite was photocured using a 2 mm
      composite inlay block as a shielding system while the adhesive was shielded by a
      2.3 mm thick wafer, composed of the inlay material and the previously cured
      bonding composite. The kinetics and levels of polymerization were measured by a
      differential scanning calorimeter technique (DSC 25, Mettler, Orange, CA,
      Toledoh, kusnacht, switzerland). RESULTS: The inlay shielded dental composite
      reaches a significantly lower level of polymerization compared to the unshielded
      composite. Inlay shielded composite, has a slower polymerization kinetic compared
      to unshielded composite. The resin adhesive shielded by the inlay-composite wafer
      reaches polymerization values not significantly different from those of the
      unshielded adhesive. SIGNIFICANCES: The degree of cure of the light-cured
      composite resins for use as a base for indirect composite restorations, may be
      severely reduced as a result of inlay shielding.

PMID- 15963563
TI  - Rapid functional assays of recombinant IP3 receptors.
AB  - Functional assays of inositol 1,4,5-trisphosphate receptors (IP3R) currently use
      45Ca2+ release methods, fluorescent Ca2+ indicators within either the ER or
      cytosol, or electrophysiological analyses of IP3R in the nuclear envelope or
      artificial bilayers. None of the methods is presently amenable to the rapid, high
      throughput quantitative analyses of IP3R function needed to address the
      structural determinants of IP3R behavior. We use a low-affinity Ca2+ indicator
      (Mag-fluo-4) to measure free [Ca2+] within the ER of permeabilized DT40 cells
      expressing only rat type 1 IP(3)R, and establish that the indicator is capable of
      reliably reporting the Ca(2+) release evoked by IP3. A 96-well fluorescence plate
      reader equipped for automated fluid additions (FlexStation, Molecular Devices) is
      used to monitor IP3-evoked Ca2+ release. The method allows quick and economical
      functional assays of recombinant IP3R in small volumes (< or = 100 microl).

PMID- 15963564
TI  - PenBase, the shrimp antimicrobial peptide penaeidin database: sequence-based
      classification and recommended nomenclature.
AB  - Antimicrobial peptides play a major role in innate immunity. The penaeidins,
      initially characterized from the shrimp Litopenaeus vannamei, are a family of
      antimicrobial peptides that appear to be expressed in all penaeid shrimps. As of
      recent, a large number of penaeid nucleotide sequences have been identified from
      a variety of penaeid shrimp species and these sequences currently reside in
      several databases under unique identifiers with no nomenclatural continuity. To
      facilitate research in this field and avoid potential confusion due to a diverse
      number of nomenclatural designations, we have made a systematic effort to
      collect, analyse, and classify all the penaeidin sequences available in every
      database. We have identified a common penaeidin signature and subsequently
      established a classification based on amino acid sequences. In order to clarify
      the naming process, we have introduced a 'penaeidin nomenclature' that can be
      applied to all extant and future penaeidins. A specialized database, PenBase,
      which is freely available at , has been developed for the penaeidin family of
      antimicrobial peptides, to provide comprehensive information about their
      properties, diversity and nomenclature.

PMID- 15963565
TI  - Effect of tuftsin on embryo vaccination with Newcastle disease virus vaccine.
AB  - The effect of tuftsin of embryo and post-hatch vaccination with NDV-F was
      studied. The embryo vaccination with NDV-F resulted in more number of dead-in
      shell embryos. To overcome this problem, the vaccine was treated separately with
      ethyl methane sulfate (EMS) and 5-fluorouracil (5-FU) and administered. Treating
      the vaccine with 5-FU resulted in better hatchability as compared to EMS
      treatment. In embryo, NDV antibody titres increased upto 2 weeks of age and
      declined thereafter, whereas in post-hatch vaccination, the antibody titre
      increased from second to fourth week of age and declined thereafter. The
      seroconversion was better when the vaccine was given along with tuftsin either to
      embryos or chicks (post-hatch vaccination) as compared to those vaccinated
      without tuftsin. Moreover, the percentage of hatchability was more in tuftsin
      administered groups. It was found that embryo vaccination can ensure definite
      protection during the early life of the chicks despite the presence of maternal
      antibodies. In cases where breeder vaccinations do not result in concomitant
      transfer of antibody to progeny chicks, embryo vaccination would give only
      neonatal resistance. During the later stages, embryo vaccination did not confer
      any advantage over post-hatch vaccination.

PMID- 15963566
TI  - In vivo neurochemical monitoring and the study of behaviour.
AB  - In vivo neurochemical monitoring techniques measure changes in the extracellular
      compartment of selected brain regions. These changes reflect the release of
      chemical messengers and intermediates of brain energy metabolism resulting from
      the activity of neuronal assemblies. The two principal techniques used in
      neurochemical monitoring are microdialysis and voltammetry. The presence of
      glutamate in the extracellular compartment and its pharmacological
      characteristics suggest that it is released from astrocytes and acts as
      neuromodulator rather than a neurotransmitter. The changes in extracellular
      noradrenaline and dopamine reflect their role in the control of behaviour.
      Changes in glucose and oxygen, the latter a measure of local cerebral blood flow,
      reflect synaptic processing in the underlying neuronal networks rather than a
      measure of efferent output from the brain region. In vivo neurochemical
      monitoring provides information about the intermediate processing that intervenes
      between the application of the stimulus and the resulting behaviour but does not
      reflect the final efferent output that leads to behaviour.

PMID- 15963567
TI  - The conceptual nervous system of J.A. Gray: schizophrenia and consciousness.

PMID- 15963569
TI  - Spontaneous resolution of binary copper(II) complexes with racemic dipeptides:
      crystal structures of glycyl-L-alpha-amino-n-butyrato copper(II) monohydrate,
      glycyl-D-valinato copper(II) hemihydrate, and glycyl-L-valinato copper(II)
      hemihydrate.
AB  - Copper(II) complexes with glycyl-DL-alpha-amino-n-butyric acid (H2gly-DL-but),
      glycyl-DL-valine (H2gly-DL-val), glycyl-DL-norleucine (H2gly-DL-norleu), glycyl
      DL-threonine (H2gly-DL-thr), glycyl-DL-serine (H2gly-DL-ser), glycyl-DL
      phenylalanine (H2gly-DL-phe), and glycyl-L-valine (H2gly-L-val), have been
      prepared and characterized by IR, powder diffuse reflection, CD and ORD spectra,
      and magnetic susceptibility measurements, and by single-crystal X-ray
      diffraction. The crystal structures of the copper complex with H2gly-DL-but, the
      copper complex with H2gly-DL-val, and [Cu(gly-L-val)]n.0.5nH2O have been
      determined by a single-crystal X-ray diffraction method. As for the structure of
      the copper complex with H2gly-DL-but, the configuration around the asymmetric
      carbon atom is similar to that of [Cu(gly-L-val)]n.0.5nH2O. Therefore it is
      concluded that the copper complex with H2gly-DL-but is [Cu(gly-L-but)]n.nH2O. On
      the contrary, as for the structure of the copper complex with H2gly-DL-val, the
      configuration around the asymmetric carbon atom is different from that of [Cu(gly
      L-val)]n.0.5nH2O. Therefore it is concluded that the copper complex with H2gly-dl
      val is [Cu(gly-D-val)]n.0.5nH2O. So during the crystallization of the copper(II)
      complexes with H2gly-DL-but and H2gly-DL-val, spontaneous resolution has been
      observed; the four complexes have separated as [Cu(gly-D-but)]n.nH2O, [Cu(gly-L
      but)]n.nH2O, [Cu(gly-D-val)]n.0.5nH2O, and [Cu(gly-L-val)]n.0.5nH2O,
      respectively. [Cu(gly-L-but)]n.nH2O is orthorhombic with the space group
      P2(1)2(1)2(1). [Cu(gly-D-val)]n.0.5nH2O and [Cu(gly-L-val)]n.0.5nH2O are
      monoclinic with the space group C2. In these complexes, the copper atom is in a
      square-pyramidal geometry, ligated by a peptide nitrogen atom, an amino nitrogen
      atom, a carboxyl oxygen atom, and a carboxyl oxygen atom and a peptide oxygen
      atom from neighboring molecules. So these complexes consist of a two-dimensional
      polymer chain bridged by a carboxyl oxygen atom and a peptide oxygen atom from
      neighboring molecules. The axial oxygen atom is located above the basal plane and
      the side chain of an amino acid is located below it. These polymer chains consist
      of only one or the other type of optical isomers; no racemic dipeptides are
      found. Therefore, spontaneous resolution has been observed in the crystallization
      of copper(II) complexes with H2gly-DL-but and H2gly-DL-val. The crystal structure
      of [Cu(gly-D-val)]n.0.5nH2O agrees almost completely with that of [Cu(gly-L
      val)]n.0.5nH2O, except for the configuration around the asymmetric carbon atom.

PMID- 15963568
TI  - The cytidine deaminases AID and APOBEC-1 exhibit distinct functional properties
      in a novel yeast selectable system.
AB  - Activation-induced cytidine deaminase (AID) is indispensable for immunoglobulin
      maturation by somatic hypermutations and class switch recombination and is
      supposed to deaminate cytidines in DNA, while its homolog APOBEC-1 edits
      apolipoprotein (apo) B mRNA by cytidine deamination. We studied the editing
      activity of APOBEC-1 and AID in yeast using the selectable marker Gal4 linked to
      its specific inhibitor protein Gal80 via an apo B cassette (Gal4-C) or via the
      variable region of a mouse immunoglobulin heavy chain gene (Gal4-VH). Expression
      of APOBEC-1 induced C to U editing in up to 15% of the Gal4-C transcripts, while
      AID was inactive in this reaction even in the presence of the APOBEC-1
      complementation factor. After expression of APOBEC-1 as well as AID approximately
      10(-3) of yeast cells survived low stringency selection and expressed beta
      galactosidase. Neither AID nor APOBEC-1 mutated the VH sequence of Gal4-VH, and
      consequently the yeast colonies did not escape high stringent selection. AID,
      however, induced frequent plasmid recombinations that were only rarely observed
      with APOBEC-1. In conclusion, AID cannot substitute APOBEC-1 to edit the apo B
      mRNA, and the expression of AID in yeast is not sufficient for the generation of
      point mutations in a highly transcribed Gal4-VH sequence. Cofactors for AID
      induced somatic hypermutations of immunoglobulin variable regions, that are
      present in B cells and a variety of non-B cells, appear to be missing in yeast.
      In contrast to APOBEC-1, AID alone does not exhibit an intrinsic specificity for
      its target sequences.

PMID- 15963570
TI  - Selective tumor targeting by enhanced permeability and retention effect.
      Synthesis and antitumor activity of polyphosphazene-platinum (II) conjugates.
AB  - Nanosized polyphosphazene-platinum (II) conjugates with a wide range of molecular
      weight from 24,000 to 115,000 were synthesized to study their tumor selectivity
      by enhanced permeability and retention (EPR) effect and their antitumor activity.
      It has been found from biodistribution study that the present polyphosphazene
      Pt(II) conjugates exhibit high tumor selectivity by EPR effect with the tumor to
      tissue ratio (TTR) from 3.6 to 13 depending on the molecular size. These polymer
      conjugates have shown excellent in vivo antitumor activity against both murine
      and human cancer cell lines. In particular, xenograft trials of the conjugates
      have shown outstanding tumor inhibition effect on the stomach cancer cell line,
      YCC-3, which is one of the least responsive to the anticancer agents currently in
      clinical use, although the reason is not clearly explainable yet. The high in
      vivo activity seems to be attributed to the controlled-release of the antitumor
      active platinum (II) moiety, [GlyGluPt(dach] (dach=trans-(+/-)-1,2
      diaminocyclohexane) from the phosphazene backbone by degradation in aqueous
      solution.

PMID- 15963571
TI  - Porcine dermatitis and nephropathy syndrome (PDNS) is associated with a systemic
      cytokine expression profile indicative of proinflammation and a Th1 bias.
AB  - Porcine dermatitis and nephropathy syndrome (PDNS) is broadly discussed as a
      porcine circovirus type 2 (PCV2)-associated disease, although PCV2, in contrast
      to postweaning multisystemic wasting syndrome (PMWS), has to date not been proven
      to be the aetiologic agent. In order to better understand the complex
      immunopathology of PDNS, the systemic cytokine expression profiles of (i) five
      pigs suffering from PDNS, (ii) five animals suffering from naturally acquired
      PMWS and (iii) five controls were investigated at mRNA and protein levels by
      means of multiplex real-time RT-PCR and flow cytometric intracellular cytokine
      detection, respectively. IL-1alpha, IL-6 and IFN-gamma mRNA expressions were
      found to be elevated in PDNS pigs. At the protein level, an increased capacity of
      peripheral blood mononuclear cells to produce IL-2, IL-4, IL-6, IL-12, TNF-alpha
      and IFN-gamma was evident. Hematological investigations revealed a hypochromic
      anemia while basophils and monocytes were relatively and neutrophils absolutely
      increased in PDNS pigs. PCV2 antibody levels did not differ significantly between
      PDNS and PMWS affected animals. Taken results together, the cytokine profile of
      the PDNS affected animals together with hematological data pointed towards a
      proinflammatory condition supporting a Th1 bias. Cytokine data of PMWS affected
      animals exhibited only minor non-significant differences when compared to
      controls, only IL-10 was significantly decreased at the mRNA level.

PMID- 15963572
TI  - Experimental Actinobacillus pleuropneumoniae infection in piglets with different
      types and levels of specific protection: immunophenotypic analysis of lymphocyte
      subsets in the circulation and respiratory mucosal lymphoid tissue.
AB  - Actinobacillus pleuropneumoniae (APP) infection in piglets results in severe and
      fatal fibrinous hemorrhagic necrotizing pneumoniae. The aim of our study was to
      analyze changes in lymphocyte subset distribution in peripheral blood,
      bronchoalveolar lavage fluid (BALF) and tracheobronchal lymph nodes (TLN) in non
      immune piglets upon a challenge with a high dose of APP and to compare the
      quality of such changes in unprotected piglets with counterparts exhibiting
      specific immunity mediated by high titers of colostrum-derived APP-specific
      antibodies and/or a low dose APP infection in the early postnatal period.
      Challenge with APP resulted in a massive increase in CD8-negative gammadelta T
      cells in parallel with a reduction in numbers of CD3-CD8low cells in BALF
      independent of the type and level of immunity and this seems to be a general
      phenomenon associated with experimental infection. An increase in B-lymphocyte
      numbers in TLN was another characteristic feature accompanying APP infection in
      all experimental groups. In piglets with colostrum-derived APP-specific
      antibodies, this was associated with higher relative numbers of IgM+CD2+
      lymphocytes in TLN, while B-cells with the CD2- surface phenotype apparently
      expanded in the absence of passive humoral immunity.

PMID- 15963573
TI  - CDR3 sequence preference of TCRBV8S2+ T cells within the CNS does not reflect
      single amino acid dependent avidity expansion.
AB  - To investigate the influence of antigen and restricting MHC class II molecule on
      the T cell repertoire, we varied the peptide source by immunizing either with
      myelin basic protein (MBP) (rat)63-88 or MBP(GUINEA PIG (GP))63-88, which differ
      in the core region of the peptide binding site at position 79 by a single
      exchange of threonine (T) to serine (S) and by altering the MHC by immunizing MHC
      congenic LEW (RT1(1)) and LEW.1W (RT1u) rats. In both MHC haplotypes both
      peptides lead to oligoclonal dominance of TCRBV8S2 expressing T cells within the
      central nervous system (CNS) as assessed by complementary determining region 3
      (CDR3) spectratyping. In contrast cytofluorometric analysis indicated that only
      MBP(GP)63-88 in context with the RT1(l) haplotype of the LEW rat lead to strong
      expansions of TCRBV8S2 expressing T cells within the CNS. Importantly, the small
      conservative change from S to T at position 79 within MBP63-88 had a strong
      influence both on the encephalitogenic potential of the peptide and on the number
      of TCRBV8S2+ T cells infiltrating the CNS. These results demonstrate that even
      minor changes in only one side chain of an amino acid within an (auto)antigen can
      dramatically alter TCR avidity for certain MHC class II/peptide complexes.

PMID- 15963574
TI  - Pathologic evaluation of routine tonsillectomy and adenoidectomy specimens in the
      pediatric population: is it really necessary?
AB  - OBJECTIVE: To evaluate the necessity of histopathologic examination for routine
      tonsillectomy and/or adenoidectomy in terms of unexpected malignancy by
      evaluating a large group of pediatric patients retrospectively with review of the
      literature. MATERIALS AND METHODS: A retrospective chart review of all patients
      under the age of 19 who underwent tonsillectomy and/or adenoidectomy between
      January 1990 and January 2005 was carried out. The records were analyzed
      concerning each patient's age, sex, indication for surgery, type of surgical
      procedure and the result of histopathologic examination of the specimen. The
      patients operated for chronic or recurrent infections and obstructive hypertrophy
      were included in the study. Moreover, the English literature was searched in
      Medline for articles published between 1949 and March 2005 and the studies
      dealing with pathologic analysis of tonsillectomy and/or adenoidectomy specimens
      were reviewed. RESULTS: The total number of patients was 2826. After excluding 83
      patients because of insufficient data, 2743 patients with an age distribution
      from 1 to 18 years (mean: 7.53) were reviewed. There were 1534 males (56%) and
      1209 females (44%). Tonsillectomy and adenoidectomy were performed together on
      1930 patients (70%) while tonsillectomy and adenoidectomy alone were performed on
      287 (10%) and 526 (20%) patients, respectively. Evaluation of the pathology
      reports revealed no malignancies. Review of the literature identified 14 articles
      and 5 of them included only pediatric patients. The rate of unexpected
      malignancies observed in these pediatric series varied between 0 and 0.18%.
      CONCLUSION: After being evaluated by an experienced otolaryngologist, pathologic
      evaluation of all specimens may not be necessary if a child undergoing routine
      tonsillectomy and/or adenoidectomy is not found to have certain preoperative risk
      factors.

PMID- 15963575
TI  - Melanotic neuroectodermal tumor in a newborn.
AB  - Melanotic neuroectodermal tumor of infancy (MNTI) is an uncommon, fast-growing,
      pigmented neoplasm of neural crest origin; it primarily affects the maxilla of
      the infants during the first year of life. Approximately 200 instances of this
      tumor are reported in the medical literature. We present a case of newborn with
      MNTI on the left maxillary alveolar ridge. The patient underwent complete
      surgical resection without maxillectomy. There has been no recurrence in a follow
      up period of 1 year. The diagnostic features and management alternatives of MNTI
      are discussed.

PMID- 15963576
TI  - Lymphoproliferative disorder of the airway of an adolescent without
      immunodeficiency.
AB  - Epstein-Barr virus (EBV) is a ubiquitous viral pathogen in humans that has a
      unique ability to immortalize B-cells. In immunosuppressed individuals, EBV can
      produce non-neoplastic lymphoproliferative disorders involving various organs. We
      describe a case report of EBV-associated lymphoproliferative disorder in an
      immunocompetent 14-year-old male. The case provides a description of EBV
      associated lymphoproliferation affecting the upper and lower respiratory tract.
      The massive submucosal infiltration of B-cells in the lingual tonsils, trachea,
      and bronchi produced near-complete airway obstruction resulting in tracheotomy.
      Neither surgical reduction of lingual tonsils nor treatment with steroids was of
      benefit. An extensive evaluation for immunodeficiency and neoplasia was normal.
      Treatment with rituximab, an anti-CD20 antibody, resulted in near-complete
      resolution of the infiltrative process, sufficient to allow decannulation.
      Rituximab is a treatment option for the rare occurrence of non-neoplastic, EBV
      associated, lymphoproliferative disorders.

PMID- 15963577
TI  - Sulfatase activity in the oyster Crassostrea virginica: its potential
      interference with sulfotransferase determination.
AB  - Two sulfatase isoforms, a soluble one with an optimum pH of 5.0, and a microsomal
      one with an optimum pH of 7.6, were observed in digestive gland, gonads, mantle
      and gills of the oyster C. virginica. The highest sulfatase activity was recorded
      in the digestive gland cytosol and is likely to interfere with the in vitro
      determination of sulfotransferase activity. Indeed, the sulfatase inhibitor
      Na(2)SO(3) led to an increase of measured sulfotransferase activity (31+/-9%),
      suggesting that those sulfatases might be partially responsible for the low
      sulfotransferase activities found in C. virginica.

PMID- 15963578
TI  - Transcriptome responses to carbon tetrachloride and pyrene in the kidney and
      liver of juvenile rainbow trout (Oncorhynchus mykiss).
AB  - We report the effects of the hepatotoxic compound carbon tetrachloride (CCl(4))
      and pyrene, a model polycyclic aromatic hydrocarbon, on the transcriptomes of
      juvenile rainbow trout kidneys and livers. Fish were exposed to sublethal doses
      for 4 days and expression of 1273 genes was measured using a cDNA microarray.
      Efforts were focused on differentiating between unspecific responses and those
      that can be regarded as molecular signatures of CCl(4) and pyrene toxicities.
      Expression profiles were analyzed in terms of Gene Ontology categories. Universal
      reactions to chemical toxicity were observed in metallothionein, HSP90 and
      mitochondrial proteins of oxidative phosphorylation, which were induced in both
      tissues. Several genes showed similar responses to both compounds in either
      kidney or liver; most of the effects are implicated in hematopoiesis and immune
      response. Stimulation of mitochondrial and heat shock proteins was greater in the
      liver than in the kidney, whereas genes involved in transcription, humoral immune
      response and apoptosis were suppressed. Pyrene and CCl(4) caused opposite effects
      on expression of several genes, including HSP-27, macrophage receptor Marco,
      metalloproteinases (MMP9 and MMP13), and delta-6 fatty acid desaturase. Pyrene
      affected mainly genes implicated in the maintenance of the genetic apparatus,
      immune response, glycolysis, and iron homeostasis. CCl(4) affected the structural
      proteins and genes involved in cellular stress, protein folding, and steroid
      metabolism. Overall, pyrene suppressed a range of protective or acclimative
      reactions, many of which were stimulated with CCl(4). Additionally, gene
      profiling analyses indicated adaptive and potentially maladaptive reactions to
      toxicity. For instance, stimulation of mitochondrial proteins coincided with
      suppression of catalase, whereas CCl(4) down-regulated fatty acid metabolism and
      peroxisomal proteins. A number of candidate biomarkers for ecotoxicological risk
      assessment were identified as our understanding of mechanisms of pyrene and
      CCl(4) toxicities in rainbow trout increased.

PMID- 15963579
TI  - An iron regulatory-like protein expressed in Plasmodium falciparum displays
      aconitase activity.
AB  - Plasmodium falciparum iron regulatory-like protein (PfIRPa) has homology to both
      mammalian iron regulatory proteins and aconitases and is capable of binding RNA
      iron response elements. We examined the subcellular localization of PfIRPa and
      its enzymatic properties at low oxygen tension. Differential digitonin
      permeabilization of isolated trophozoites with subsequent Western blot analysis
      suggests that the localization of PfIRPa is predominantly in the membranous
      compartments of the parasite, such as the mitochondrion. Immunofluorescence
      analysis showed that PfIRPa colocalizes with heat shock protein 60 (Hsp60), a
      mitochondrial marker, and is also present in the parasitic cytosol/food vacuole.
      Under conditions favoring the formation of an iron-sulfur cluster, recombinant
      PfIRPa (rPfIRPa) had aconitase activity as detected by a colorimetric NADPH-MTT
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. As
      assessed by the hydration of cis-aconitate spectrophotometrically at 240 nm,
      rPfIRPa had high affinity for cis-aconitate (Km=3.5 microM) but a low turnover
      number (Kcat= 3.3 s(-1)). The overall catalytic efficiency (Kcat/Km) of rPfIRPa
      was similar in magnitude to human cytosolic IRP1/aconitase and human
      mitochondrial aconitase. PfIRPa immunoprecipitated from parasite lysates also had
      aconitase activity, as assessed by an MTT-based assay. Our results provide
      evidence that PfIRPa localizes in the mitochondrion and in the cytosol/food
      vacuole and is able to demonstrate aconitase activity. Further understanding of
      the role of PfIRPa/aconitase in the regulation of P. falciparum homeostasis may
      contribute towards the development of novel antimalarial strategies against
      plasmodial species.

PMID- 15963580
TI  - Elderly psychiatric patients at risk of folic acid deficiency: a case controlled
      study.
AB  - In the elderly, folic acid deficiency may result in psychiatric symptoms or the
      increases in severity of other organic and non-organic mental diseases. We aimed
      to characterize elderly, community-dwelling, newly admitted patients to a large
      urban psychiatric hospital who are suffering from untreated folic acid deficiency
      in comparison with elderly inpatients who do not suffer from this deficiency.
      During a 2-year period, all subjects aged 65 years or older admitted to the large
      psychiatric center were tested for levels of serum folic acid levels. Subjects
      suffering from folic acid deficiency were compared (unpaired t-test) with matched
      patients with normal serum levels. Of the 293 newly admitted elderly patients 45
      (15.7%) suffered from folic acid deficiency. Mean age for the folic acid
      deficient group was 77.3+/-8.1 years, 38% were diagnosed as suffering from
      dementia, 22% were depressed and 51% were living alone. In the comparison group
      mean age was 77.3+/-6.3 years, 33% were diagnosed as suffering from dementia, 24%
      were suffering from depression and 57% were living alone. We conclude that we
      could not find any "characteristic" of elderly subjects at risk of folic acid
      deficiency.

PMID- 15963581
TI  - Larger hip circumference independently contributed to reduced metabolic risks in
      Tehranian adult women.
AB  - BACKGROUND: It has been suggested that health professionals may discard
      measurement of hip circumference from public health screening efforts. Before
      discarding the hip circumference in epidemiological surveys, it is important to
      consider whether any important information is likely to be lost. OBJECTIVE: To
      evaluate the relationship between hip circumference and metabolic risk factors in
      an urban adult population of Tehranian women. DESIGN: In this population-based
      cross-sectional study, a representative sample of 5720 women aged 18-74 years,
      were included. Demographic data was collected; anthropometric indices and blood
      pressure were measured according to standard protocol. Hypertension was defined
      based on Joint National Committee VI (JNC VI). Biochemical analysis was conducted
      on fasting blood samples. Diabetes was defined as fasting plasma glucose (FPG) >
      or =126 mg/dl or 2-h plasma glucose (2hPG) > or =200 mg/dl. Lipid disorders and
      components of metabolic syndrome were considered based on Adult Treatment Panel
      III (ATP III). RESULTS: Mean age of women was 39.9+/-14.6 years. Mean body mass
      index, waist-to-hip ratio, waist and hip circumferences for subjects were 27.1+/
      5.1 kg/m2, 0.83+/-0.08, 86.5+/-13.1 cm and 103.5+/-9.8 cm, respectively. Higher
      hip circumference was associated with lower levels of serum total- and LDL
      cholesterol, serum triglyceride, fasting plasma glucose, 2-h plasma glucose,
      systolic and diastolic blood pressure. Subjects in the top quintile of hip
      circumference had higher values of serum HDL-cholesterol concentration compared
      to those in the lower category. After adjustment for potential confounding
      variables and anthropometric measures associated with higher hip circumference, a
      significant decreasing trend was observed for odds of having high LDL-cholesterol
      (odds ratios among quintiles: 1.00, 0.98, 0.97, 0.95, 0.84, respectively, P for
      trend=0.04), diabetes (1.00, 0.68, 0.58, 0.45, 0.42, P for trend=0.01),
      hypertension (1.00, 0.96, 0.82, 0.78, 0.70, P for trend 0.02), low serum HDL
      cholesterol (1.00, 1.03, 0.86, 0.82, 0.56, P for trend=0.04), elevated blood
      pressure (1.00, 0.99, 0.82, 0.70, 0.61, P for trend=0.01) and abnormal glucose
      homeostasis (1.00, 0.69, 0.66, 0.54, 0.48, P for trend=0.01) among hip
      circumference quintile categories. Individuals in the upper category of hip
      circumference had lower odds of having hypercholestrolemia (0.86 vs. 1.00) and
      high serum triglyceride levels (0.74 vs. 1.00) compared to those in the lowest
      category. CONCLUSION: Hip circumference is independently and inversely associated
      with metabolic risk factors. This study underscores the importance of continuing
      to measure hip circumference in epidemiologic surveys in Tehranian adult women.

PMID- 15963582
TI  - Younger age potentiates post myocardial infarction survival disadvantage of
      women.
AB  - BACKGROUND: Female patients with acute myocardial infarction (MI) exhibit higher
      unadjusted in-hospital mortality rates compared to male patients. However,
      contradictory evidence exists on whether this survival disadvantage disappears
      after adjustment for age and other prognostic factors. This study, based on a
      countrywide survey of consecutive unselected patients with acute MI, examined
      whether female gender is an independent predictor of poor short-term outcome and
      less intensive in-hospital treatment. METHODS: Data on a total of 7433 patients
      were analyzed. RESULTS: The mean age was 64+/-13 years and the proportion of
      females in this population was 23%. Univariate and multivariate predictors of in
      hospital mortality in female patients were estimated. Unadjusted in-hospital
      mortality rates of women were significantly higher compared to men (17.7 vs. 8.6,
      p<0.001). In multivariate analysis, female gender was an independent predictor of
      in-hospital mortality in the total population [relative risk (RR)=1.29, 95%
      confidence interval (CI)=1.02-1.64, p=0.036]. The RR of women for in-hospital
      death was exaggerated among younger patients, aged <55 years (RR=3.84, 95%
      CI=1.07-13.74, p=0.039). Female gender was also independently and inversely
      associated with administration of thrombolytic treatment (RR=0.724, 95% CI=0.630
      0.831, p=<0.001). CONCLUSION: Although female gender is an independent predictor
      of higher post-MI in-hospital mortality with a pronounced effect among younger
      patients, women are less likely to receive thrombolysis than men. Based on the
      results from this countrywide study, we should consider women, especially of
      younger age, as patients at particular high risk, who contrary to common
      practice, deserve more intensive and aggressive in-hospital treatment.

PMID- 15963583
TI  - Sport practice and the risk of lone atrial fibrillation: a case-control study.
AB  - BACKGROUND: Lone atrial fibrillation (LAF) is characterized by the presence of
      atrial fibrillation in the absence of structural heart disease or other
      identifiable cause of arrhythmia. In a recent study, we reported sport practice
      to be more frequent in LAF patients than in the general population. The aim of
      the study was to determine the association between sport practice and the
      prevalence of LAF in men. METHODS: An age-matched case-control study was
      designed. Cases were identified from consecutive patients who attended an
      outpatient clinic; 51 men with LAF were included, 20 of them with vagal
      characteristics. Controls were selected from the general population (n=109). A
      questionnaire to assess former and current sport practice and the number of
      lifetime hours of sport practice was administered. Conditional logistic
      regression was used for statistical analysis. RESULTS: The proportion of patients
      with LAF who reported current sport practice (31%) was higher than that observed
      in controls (14%). In the logistic regression, current practice of sport was
      associated with a higher prevalence of LAF (OR=3.13; 95% CI: 1.39-7.05). The
      practice of more than 1500 lifetime hours of sport appears to be the threshold
      for the observed association. Current practice of sport with a lifetime practice
      greater than 1500 h was associated with LAF (OR=2.87; 95% CI: 1.20-6.91).
      CONCLUSION: In men, the combination of current and prolonged lifetime sport
      practice is associated with higher risk of LAF.

PMID- 15963584
TI  - Herd-level factors associated with isolation of Salmonella in a multi-state study
      of conventional and organic dairy farms II. Salmonella shedding in calves.
AB  - The objective of this study was to evaluate associations between herd-level
      factors and the isolation of Salmonella in calves from dairy farms in Minnesota,
      Wisconsin, Michigan and New York. Study farms were 129 conventional and organic
      farms enrolled without regard to previous history of Salmonella infection. Herds
      were sampled at 2-month intervals over a 1-year period. Salmonella was isolated
      in fecal samples from 176 (3.8%) of 4673 preweaned calves with 40 (31.0%) of 129
      farms having at least one positive calf sample over the course of the study.
      Multivariable logistic regression using the generalized estimating equations
      approach was used to evaluate risk factors for Salmonella shedding after
      adjustment for effects of herd size, season, state of origin and the multiple
      sampling occasions per herd. Factors retained in the final model that were
      associated with an increased odds for Salmonella shedding were lack of routine
      feeding of milk replacer containing antimicrobials to preweaned calves (OR=2.8,
      95% CI: 1.4, 5.8), use of maternity housing as a hospital area for sick cows more
      than once a month (OR=2.1, 95% CI: 1.1, 4.0), and cow prevalence level by visit,
      categorized into the following four-levels: > or =20% (OR=11.6, 95% CI: 5.7,
      23.7), 10-19.9% (OR=4.7, 95% CI: 2.0, 11.5), 0.1-9.9% (OR=3.6, 95% CI: 1.5, 8.7)
      and 0% (reference level). Herd size was not associated with Salmonella shedding
      in the final multivariable model.

PMID- 15963585
TI  - Feasibility of assessment of regulatory lipids in breath condensate as potential
      presymptomatic harbingers of pulmonary pathobiology.
AB  - Regulatory lipids from the airway surface readily form aerosols that can be
      recovered non-invasively by cooling expired breath to form breath condensate
      (BC). Regulatory lipids have been detected previously utilizing enzyme-linked
      immunosorbent serologic assay (ELISA). Here we test the feasibility of assessment
      of regulatory lipids in BC by mass spectrometry so presently unknown lipid
      regulatory components can be detected without addition of specific antibodies as
      in the ELISA procedure. Baseline regulatory lipids were detected in >pg/mL BC in
      control animals or human lung tissue culture cells. In nearly every case animals
      exposed to toxins or infectious bacteria showed increases in the BC regulatory
      components. Lipids were recovered from BC by solid phase extraction.
      Phosphatidylcholine (PC) based lipids were detected as the progenitor (parent)
      ions of isomers that fragmented in producing product positive ions at m/z 184 (of
      phosphocholine) in tandem MS using capillary HPLC and electrospray ionization. BC
      eicosanoids such as prostaglandins, thromboxane, and isoprostanes require
      capillary gas chromatography for separation and detection that necessitates
      methoximation, pentafluorobenzyl (PFB) ester formation, and trimethyl silylation
      of hydroxyls prior to gas chromatography/ion trap tandem mass spectrometry of
      negative ions after chemical ionization (NICI). Tetradeuterated internal
      standards were utilized for quantitation with the GC/NICI/MS. Changes in
      concentrations of lipids and eicosanoids were observed in piglets, and rats
      exposed to aerosolized 100 mug/kg lipopolysaccharide (LPS), or 50 mug/kg and 150
      mug/kg aerosolized Staphylococcal enterotoxin B (SEB) in BC as well as in human
      THP-1 cell culture cell supernatants and bronchoalveolar lavage (BAL) samples in
      rats. Responses of the molecular species of phosphatidylcholines (PCs), platelet
      activating factors (PAFs) and specific eicosanoids correlated to the toxin and
      bacterial infections suggesting that patterns of differential responses could be
      detected with further experimentation. Initial targets included prostaglandins
      (PGE(2), PGF(2alpha)), thromboxane (TXB2), and prostacyclin (as 6-Keto
      PGF(1alpha)) that show differential responses to inflammation, the leukotriene
      (LTB4) and PGD2 for allergic responses, isoprostanes (8-iso-PGF(2alpha)) for free
      radical oxidative stress responses, and HETEs for differential lipoxygenase
      activities. PAFs and lysoPAFs have been shown to increase with inflammation and
      in the feasibility experiments reported here. Preliminary studies show pulmonary
      responses of piglets to intrathecal exposure of toxicants (LPS and SEB) or
      infections with Actinobacillus pleuropneumoniae induce increased levels of lipids
      and two eicosanoids with the suggestion that differential patterns might be
      detected with expanded testing. Preliminary experience indicates numerous other
      eicosanoids were available for assay in BC. This suggests an important potential
      application of BC to observe a wide array of factors to establish comprehensive
      profiles for physiological and pathophysiological states. Ultimately this
      technique could be used as a non-invasive possibly presymptomatic assessment of
      pulmonary pathobiology.

PMID- 15963586
TI  - Mood effects on the ERP processing of emotional intensity in faces: a P3
      investigation with depressed students.
AB  - This study examined mood-relevant emotion processing in depression using event
      related potentials (ERPs). Cognition in depression has been characterized as
      having attention and memory biases for negative (or mood relevant) information
      and away from positive (or mood incongruent) information, however, the time
      course and specificity of this processing during the perception of emotional
      expressions is not well known. In order to index specific information processing
      stages a visual oddball task with facial stimuli was utilized, with neutral
      expressions as the standard and targets varying on valence (happy and fear) and
      intensity (40%, 70% or 100% emotive) dimensions. Participants were 36 university
      students grouped according to their BDI-II scores; 18 non-depressed controls (BDI
      II<or=eight; M=4.1) and 18 depressed (BDI-II>or=15, M=25.5), age- and sex-matched
      between groups. Mixed model ANOVAs revealed interactions between control and
      depressed participants with happy and fearful stimuli showing significantly
      reduced P3 amplitudes and P3 latencies for happy faces as well as significantly
      delayed P3 latencies specifically for 40% happy faces in depressed participants.
      These findings are interpreted as evidence for a diminished cognitive processing
      ability during emotion discrimination for low-intensity mood incongruous (happy)
      faces in depression.

PMID- 15963587
TI  - Role of proprioceptive information in movement programming and control in 5 to 11
      year old children.
AB  - The role of proprioceptive inputs in the control of goal-directed movements was
      examined, by means of the tendon vibration technique, in 5 to 11-year old
      children performing a serial pointing task. Children pointed, with movements of
      various amplitudes and at various positions, by alternating wrist flexions and
      extensions. Tendon vibration was applied to both agonist and antagonist muscles
      to perturb relevant muscular proprioceptive inputs during the static or dynamic
      phase of the task, i.e., during stops on targets or during movement execution.
      Constant and variable amplitude errors as well as constant position error were
      evaluated. Vibratory perturbation applied during movement execution resulted in a
      similar reduction in movement amplitude, yielding an increased constant error in
      all age groups and a systematic position error in the direction of the movement
      starting point. Perturbing proprioception during static phases preceding movement
      resulted in an age-related increase in the variable amplitude error, which was
      maximal in 5-year old children performing extension movements. The results were
      interpreted in terms of the use of proprioceptive information in the feedforward
      and feedback based components of movement control in children. In particular, the
      results indicated (1) developmental changes in the relative weighting of each
      component, (2) an increased capacity to move from one strategy to the other,
      depending on the availability of information, and (3) developmental changes from
      an alternated to an integrated control of amplitude and position in serial
      pointing.

PMID- 15963588
TI  - Limiting the recruitment of degrees of freedom reduces the stability of
      perception-action patterns.
AB  - The goal of the present study was to examine how recruiting/suppressing degrees
      of freedom affects the (differential) stability of two rhythmic perception-action
      patterns. In particular, participants synchronized either adduction-on-the-beat
      or abduction-on-the-beat movements of the right index finger with an auditory
      metronome. The stability of both patterns as performed in the horizontal plane
      was predicted to depend on the utilization, or recruitment, of the vertical plane
      of motion. Movements of the index finger were either free or physically
      restricted to the horizontal plane. The results showed that in the free
      condition, the vertical plane was recruited more in the more stable pattern
      (abduction-on-the-beat) than in the less stable pattern (adduction-on-the-beat).
      In the constrained condition, abduction-on-the-beat pattern was destabilized,
      whereas the stability of the adduction-on-the-beat pattern was preserved. These
      results suggest that the recruitment of the vertical plane of motion in the
      abduction-on-the-beat movements brought about an increase in the stability of
      this pattern. More generally, the trade-off between the stability of coordination
      patterns in the horizontal plane is based on a self-organizing process of
      recruitment in which neuromuscular factors are an intrinsic aspect.

PMID- 15963589
TI  - Polymorphisms of heat shock protein 70 gene (HSPA1A, HSPA1B and HSPA1L) and
      schizophrenia.
AB  - The heat shock protein 70 (HSP70) is believed to be involved in the pathogenesis
      of schizophrenia with regards to neurodevelopment. An aberration in the HSP70 has
      been proposed in schizophrenia patients, suggesting that it is a candidate gene
      for schizophrenia. This study aimed to investigate the association between the
      three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B)
      and schizophrenia. One hundred and sixty-one patients with schizophrenia and 165
      controls were enrolled in the study. A polymerase chain reaction (PCR) with a
      restriction fragment length enzyme (RFLP) was used to genotype the HSPA1A, HSPA1L
      and HSPA1B polymorphisms. There were no significant differences in the allelic or
      genotype frequencies of the HSPA1A and HSPA1L polymorphisms between the
      schizophrenia patients and the controls, while there was a marginal difference in
      the genotype frequency of the HSPA1B polymorphisms, and a significant difference
      in the allelic frequency of the HSPA1B polymorphisms between the schizophrenia
      patients and the controls. There was no evidence of an association between the
      clinical variables and schizophrenia across the genotypes among the three HSP70
      gene polymorphisms. These results suggest that a HSPA1B polymorphism might be
      related to the pathogenesis of schizophrenia at least in the Korean population.
      Therefore, larger studies from different ethnic groups should be performed to
      confirm these results.

PMID- 15963590
TI  - Efficient production and recovery of diterpenoid tanshinones in Salvia
      miltiorrhiza hairy root cultures with in situ adsorption, elicitation and semi
      continuous operation.
AB  - In Salvia miltiorrhiza hairy root cultures, the desired secondary metabolites
      diterpenoid tanshinones are normally produced at low yields and stored within the
      roots. To enhance tanshinone production and the secondary product recovery, we
      employed three means, elicitation with a yeast elicitor (YE), in situ adsorption
      of tanshinones with a hydrophobic polymeric resin (X-5) and semi-continuous mode
      of operation. YE treatment stimulated the tanshinone biosynthesis, increasing the
      total tanshinone (TT) content of root by about two-fold, from 0.46 to 1.37 mg/g
      dry weight (dw) (TT content=total content of three major tanshinones,
      cryptotanshinone, tanshinone I and tanshinone IIA). The addition of X-5 resins to
      the culture only increased the tanshinone yield slightly, but recovered more than
      80% of tanshinones from the roots. With the application of a semi-continuous
      culture process involving repeated medium renewal, elicitor addition and resin
      replacement, starting at the late exponential growth phase, the root biomass was
      increased to 30.5g dw/l (versus 8-10g dw/l in batch mode) and the volumetric
      tanshinone yield to 87.5mg/l (about 15-fold increase), with 76.5% adsorbed to the
      resin. The volumetric productivity of total tanshinone reached 1.46 mg/lday, more
      than 7.4 times that of the batch culture. The results demonstrate that the
      integration of multiple elicitation, in situ adsorption and semi-continuous
      operation can synergistically enhance tanshinone production in S. miltiorrhiza
      hairy root cultures.

PMID- 15963591
TI  - Improving the amylolytic activity of Saccharomyces cerevisiae glucoamylase by the
      addition of a starch binding domain.
AB  - Glucoamylase produced by amylolytic strains of Saccharomyces cerevisiae (var.
      diastaticus) lacks a starch binding domain that is present in homologous
      glucoamylases from Aspergillus niger and other filamentous fungi. The absence of
      the binding domain makes the enzyme inefficient against raw starch and hence
      unsuitable for most biotechnological applications. We have constructed a hybrid
      glucoamylase-encoding gene by in-frame fusion of the S. cerevisiae STA1 gene and
      DNA fragment that encodes the starch binding domain of A. niger glucoamylase. The
      hybrid enzyme resulting from expression of the chimeric gene in S. cerevisiae has
      substrate binding capability and hydrolyses insoluble starch, properties not
      present in the original yeast enzyme.

PMID- 15963592
TI  - Assessment of sequence diversity in the 5'-terminal region of Citrus tristeza
      virus from India.
AB  - Twenty-one Citrus tristeza virus (CTV) isolates from India were characterized,
      using genotype-specific multiple molecular markers (MMM) from the 54'-terminal
      region and two other overlapping primer pairs (CN487/489 and CN488/491) from
      ORF1a (697-1484 nucleotides (nt)). The 5'-terminal genotype-specific primer pairs
      amplified about 500 bases from the 5'-end of the CTV genomic RNA (gRNA). With the
      three different MMM, the VT genotype-specific primers amplified 19 Indian CTV
      isolates. The T30-specific primers amplified five isolates, and the T36 primer
      amplified only one isolate T36. All isolates were amplified with CN488/491
      primers; however, only 20 isolates were amplified with CN487/489 pair. A
      phylogenetic tree, derived from the sequences of the different MMM primer
      amplified products, placed all the isolates into four distinct genogroups. Three
      of these four groups were typified by the reference isolates T30, T36, and VT.
      The fourth group, represented by the isolate BAN-2, was considered as a new
      genogroup. A phylogenetic tree based on sequences of the CN487/491 amplified
      products and other published sequences placed all of the isolates in eight
      genogroups. Phylogenetic correlation over the three different regions sequences
      of these CTV isolates showed more sequence variability between 1082 and 1484nt
      than between 1 and 500 or 697-1105 nt of the CTV gRNA. Based on three different
      5' regions sequences and phylogenetic analysis, it is hypothesized that isolates
      BAN-1, BAN-2, and B165 are three naturally occurring variants that add to the
      complexity of the CTV populations in India.

PMID- 15963593
TI  - Characteristics of nitrogen release from synthetic zeolite Na-P1 occluding
      NH4NO3.
AB  - Zeolites can accommodate a considerable amount of occluded salt such as NH4NO3,
      which can serve as a good source of slow-release plant nutrient. This study
      evaluates the kinetics of ion release from NH4NO3-occluded Na-P1 (N-NaP) using a
      simulated soil solution and deionized water as leaching solutions. The patterns
      of ion releases were examined as a function of leaching time under both static
      and continuous-flow conditions for more than one month. Releases of both NH4+ and
      NO3- from N-NaP were found to be slow and steady under both the above conditions.
      The soil solution affected the release of NH4+ and NO3- differently, while
      deionized water released nearly the same equivalents of these ions. This clearly
      indicates that ion release from salt-occluded zeolite involves two different
      reactions, cation exchange and dissolution. The kinetics of ion release from
      occluded NH4NO3 under static condition was best described by the standard Elovich
      model while the power function model best expressed these under continuous-flow
      condition. The initial ion release patterns under both conditions exhibited
      considerable deviation from the simulated models, probably as a result of the
      presence of hydrated occluded NH4NO3. Flow condition and the presence of
      electrolytes in leaching solution affected the release kinetics significantly.
      Release of occluded NH4NO3 was delayed by the presence of the NH4NO3 coated on
      zeolite crystals. These results indicate that the ion release property of
      occluded salt could be predicted and controlled. This study clearly shows that
      NH4NO3-occluded zeolites could be developed as slow release fertilizers.

PMID- 15963594
TI  - Late diabetes complications and non-dipping phenomenon in patients with Type 1
      diabetes.
AB  - BACKGROUND: Cardiovascular autonomic neuropathy (CAN) has been thought to
      underlie the loss of normal nocturnal blood pressure dipping, which is associated
      with a higher risk for nephropathy in Type 1 diabetes. Previous analyses also
      suggest however that nephropathy is a major predictor of subsequent CAN.
      OBJECTIVE: To investigate links between non-dipping phenomenon (NDP) and
      complications, particularly CAN and nephropathy. METHODS: 24-h ambulatory blood
      pressure monitoring was performed on 61 consecutively recruited subjects (mean
      age: 38.5+/-8.1, mean duration: 29.5+/-8.2 years) from the Pittsburgh
      Epidemiology of Diabetes Complications cohort (658 subjects with childhood onset
      Type 1 diabetes diagnosed between 1950 and 80). NDP was diagnosed if nocturnal
      fall of both systolic and diastolic blood pressure was <10% of the average
      daytime blood pressure. CAN was detected by abnormal (<or=1.1)
      expiration/inspiration heart rate ratio. Proteinuria was established by abnormal
      (>20 microg/min) albumin excretion rate (AER) in at least two of three timed
      urines. RESULTS: Non-dippers (n=17) had greater LDLc (p=0.012) and AER (p=0.052)
      and a higher frequency of nephropathy (OR=3.6, 95% CI=1.0-12.6) and proliferative
      retinopathy (OR=5.1, 95% CI=1.3-20.3) compared to the 44 dippers. CAN and NDP
      were not associated. In multivariate analyses, adjusting for CAN, proteinuria was
      significantly related to NDP (OR=3.6, 95% CI=1.0-12.6), an association that
      further modeling suggests was related to interactions between nephropathy, LDLc
      and hypertension. CONCLUSIONS: These data suggest a strong link between NDP and
      proteinuria which is independent of CAN and may be modified by LDLc and
      hypertension.

PMID- 15963595
TI  - Type 1 diabetes and leg length.

PMID- 15963596
TI  - Up-regulation of nNOS and associated increase in nitrergic vasodilation in
      superior mesenteric arteries in pre-hepatic portal hypertension.
AB  - BACKGROUND/AIMS: Splanchnic arterial vasodilation in portal hypertension has been
      attributed largely to vascular NO overproduction. Three NO-synthase (NOS)
      isoforms have been identified of which e(ndothelial)-NOS has been found up
      regulated and i(nducible)-NOS not expressed in the splanchnic circulation in
      portal hypertension. So far, n(euronal)-NOS has not been investigated and hence,
      the current study evaluates nNOS-expression and nNOS-mediated vasorelaxation in a
      model of portal vein-ligated rats (PVL). METHODS: Mesenteric vasculature of PVL
      and sham rats was evaluated for nNOS-protein (immunohistochemically and Western
      blotting). In vitro perfused de-endothelialized mesenteric arterial vasculature
      was pre-constricted with norepinephrine (EC(80)) and tested for nNOS-mediated
      vasorelaxation by periarterial nerve stimulation (PNS, 2-12 Hz, 45V) before and
      after incubation with the NOS-inhibitor L-NAME (10(-4)M). RESULTS: nNOS was
      localized to the adventitia of the mesenteric arterial tree showing more intense
      staining and increased protein expression in PVL as compared to sham rats. PNS
      induced a frequency-dependent vasorelaxation, which was more pronounced in PVL
      rats. L-NAME abolished this difference in nerval-mediated vasorelaxation, the
      effect being significantly greater in PVL than in sham animals. CONCLUSIONS:
      Perivascular nNOS-protein expression is enhanced in mesenteric arteries in portal
      hypertension mediating an increased nerval NO-mediated vasorelaxation. This nNOS
      derived NO overproduction may play an important role in the pathogenesis of
      arterial vasodilation in portal hypertension.

PMID- 15963597
TI  - Recombinant HBsAg inhibits LPS-induced COX-2 expression and IL-18 production by
      interfering with the NFkappaB pathway in a human monocytic cell line, THP-1.
AB  - BACKGROUND/AIMS: Hepatitis B virus suppresses the human immune-system and HBsAg
      inhibits the induction of cytokines by LPS in human macrophages, but the
      mechanisms involved remain unclear. COX-2 and its product, PGE2, play a role in
      hepatitis B and IL-18 has also been shown to inhibit HBV infection in vivo. We
      investigated whether rHBsAg affects induction of COX-2 and IL-18 by LPS and, if
      so, which signal pathways are involved in a human monocytic cell line, THP-1.
      METHODS: Cell culture, Western blotting for COX-2, ERK and IKB-alpha,
      immunofluorescence for HBsAg and NFkappaB protein and ELISA for PGE2, IL-18 and
      IL-12 were performed. RESULTS: rHBsAg inhibits LPS-induced COX-2 expression in a
      time- and dose-dependent manner by blocking the ERK and NFkappaB pathways. LPS
      induced IL-18 production was also down-regulated by rHBsAg by interfering mainly
      with the NFkappaB pathway. PGE2 reversed the inhibition of LPS-induced IL-18
      production by rHBsAg. rHBsAg was also found to inhibit the induction of IL-12 by
      LPS in THP-1 cells. CONCLUSIONS: These results showed a novel anti-inflammatory
      property of rHBsAg which involves inhibition of COX-2 and suggested that
      hepatitis B virus may regulate IFN-gamma production by inhibiting IL-18 and IL-12
      production.

PMID- 15963598
TI  - Ontogeny of AMPA and NMDA receptor gene expression in the developing sheep white
      matter and cerebral cortex.
AB  - This study examined the hypothesis that the high prevalence of white matter
      injury in premature infants is associated with increased expression of calcium
      permeable forms of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) subtype of glutamate receptors in pre-myelinating white matter. We
      characterized expression of subunits of the AMPA, and for reference, the N-methyl
      d-aspartate (NMDA), glutamate receptors at 0.5, 0.65, 0.85, and term gestation in
      the ovine fetal white matter and cerebral cortex. There was a low expression of
      the critical calcium-impermeable AMPA receptor GluR2 subunit in subcortical white
      matter both absolutely and relative to other AMPA subunits throughout gestation.
      In contrast, GluR2 subunit mRNA expression fell in the cerebral cortex with
      increasing gestation whereas protein expression increased. These findings suggest
      a vulnerability of subcortical white matter to AMPA receptor-mediated calcium
      toxicity throughout the second half of gestation. Thus, the hypothesis that AMPA
      receptor-mediated glutamate toxicity contributes to brain damage in premature
      infants needs to be revised.

PMID- 15963599
TI  - The KCNQ5 potassium channel from mouse: a broadly expressed M-current like
      potassium channel modulated by zinc, pH, and volume changes.
AB  - The KCNQ proteins compose a sub-group of the voltage-activated potassium channel
      family. The family consists of five members (KCNQ1 to 5--also named Kv7.1 to
      Kv7.5) encoded by single genes, which all give rise to proteins forming slowly
      activating potassium-selective ion channels. The physiological importance of the
      KCNQ channel family is emphasized by the fact that mutations in four of the five
      genes have been linked to human pathologies (KCNQ1 to 4). Here, we present the
      cloning and characterization of a novel KCNQ5 ortholog from mouse isolated by
      homology cloning from total mouse brain RNA (GenBank accession number: AY679158).
      The predicted protein is 95% identical to human KCNQ5. Upon expression in Xenopus
      oocytes, these proteins form voltage-dependent slowly activating channels with
      half-maximal activation at -21 mV. Our functional characterization revealed three
      novel modes of modulation: pH-dependent potentiation by Zn2+ (EC50 = 21.8 microM
      at pH 7.4), inhibition by acidification (IC50 = 0.75 microM; pKa = 6.1), and
      regulation by small changes in cell volume. Furthermore, the channels are
      activated by the anti-convulsant drug retigabine (EC50 = 2.0 microM) and
      inhibited by the M-current blockers linopiridine and XE-991. Finally, real-time
      RT-PCR was used to quantify the expression profile in a wide range of mouse
      tissues. These experiments revealed a relatively broad expression pattern in the
      nervous system but also expression in other tissues. Highest overall expression
      levels were observed in cortex and hippocampus. This study shows that murine
      KCNQ5 channels, in addition to sharing biophysical and pharmacological
      characteristics with the human ortholog, are tightly regulated by physiological
      stimuli such as changes in extracellular Zn2+, pH, and tonicity, thus adding to
      the complex regulation of these channels.

PMID- 15963600
TI  - AMPA/kainate receptor antagonist DNQX blocks the acute increase of Per2 mRNA
      levels in most but not all areas of the SCN.
AB  - The daily light:dark cycle synchronizes the circadian timing system by resetting
      the phase of the circadian pacemaker on a daily basis. Light acutely increases
      mRNA levels of the clock genes Per1 and Per2 in the suprachiasmatic nucleus
      (SCN), the site of the primary circadian pacemaker in mammals. Light is conveyed
      to the SCN through the retinohypothalamic tract (RHT), an efferent projection
      from retinal ganglion cells that releases the excitatory amino acid (EAA)
      neurotransmitter glutamate in the SCN. EAA receptor activation in the SCN is
      critical for the ability of light to phase-shift the circadian pacemaker. In a
      previous study, we demonstrated that EAA receptor activation is necessary and
      sufficient for light to acutely increase Per1 mRNA levels in the SCN. In the
      current study, we determined whether EAA receptor activation in the SCN is
      necessary for the ability of light to increase Per2 mRNA levels in the SCN in
      Syrian hamsters. The NMDA receptor antagonist AP5 and the AMPA/kainate receptor
      antagonist DNQX inhibited the ability of light and NMDA to acutely increase Per2
      mRNA levels in the SCN. In hamsters injected with DNQX, Per1 and Per2 mRNA levels
      remained slightly elevated in the ventrolateral SCN, suggesting that AMPA/kainate
      receptor activation in this region is not critical for the effects of light on
      the circadian pacemaker.

PMID- 15963601
TI  - Does incineration turn infectious waste aseptic?
AB  - Incineration of infectious waste is considered to be biologically safe. We
      performed basic experiments to confirm that bacillus spores are killed by
      incineration in a muffle furnace. Biological samples containing 10(6) spores of
      Bacillus stearothermophilus were placed in stainless steel Petri dishes and then
      into hot furnaces. The furnace temperature and duration of incineration were 300
      degrees C for 15 min, 300 degrees C for 30 min, 500 degrees C for 15 min, 500
      degrees C for 30 min and 1100 degrees C for 3 min. We confirmed that all spores
      of B. stearothermophilus were killed at each of these settings. The effect of
      incineration seems to be equivalent to that of sterilization, based on the
      satisfactory sterilization assurance level of 10(-6).

PMID- 15963602
TI  - Systemic administration of lipopolysaccharide upregulates angiotensin II
      expression in rat renal tubules: immunohistochemical and ELISA studies.
AB  - We investigated whether angiotensin II (AII) peptide is induced in the rat kidney
      under endotoxemic conditions. Immunohistochemistry revealed strong AII-like
      immunoreactivity in the renal tubules of rats given high-dose lipopolysaccharide
      (LPS; 1000 microg/kg) intraperitoneally (i.p.). AII-like immunoreactivity in
      renal tubules was slight at 1h after the LPS injection, but marked at 3 h. There
      were few signals in the kidney in saline-injected control rats. When injected at
      0.1, 10, or 1000 microg/kg i.p., LPS-induced a dose-related increase in AII-like
      immunoreactivity in renal tubules that was unaffected by treatment with the
      prostaglandin-synthesis blocker indomethacin. ELISA measurement of the AII
      concentration in the whole kidney supported the above findings. These results
      suggest that systemically administered LPS induces AII peptide expression in
      renal tubules by a prostaglandin-independent mechanism.

PMID- 15963603
TI  - The relation between melanocortin 1 receptor (MC1R) variation and the generation
      of phenotypic diversity in the cutaneous response to ultraviolet radiation.
AB  - The melanocortin 1 receptor (MC1R) is known to play an important role in
      determining physiological variation in human pigmentation, and consequently human
      susceptibility to ultraviolet radiation. A reason for wider interest is that the
      considerable phenotypic diversity has been in part generated by the effects of
      gene dosage, and the presence of a large number of mutations at this G-protein
      coupled receptor that are not functionally equivalent. Thus, a range of mutations
      at a single receptor locus can lead to a complex range of graded phenotypes.

PMID- 15963604
TI  - Special issue in honor of professor Ch.R.K. Murthy.

PMID- 15963605
TI  - The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity
      of tetraphenylporphyrin.
AB  - Several strategies have been proposed to improve the efficiency of
      photosensitizers used in photodynamic therapy (PDT). In this context, the
      synthesis of mono- (1) and di-glucosylated (2) porphyrins, and mono-glucosylated
      chlorin (3) was performed. HT29 human adenocarcinoma cells were significantly
      more sensitive to asymmetric and less hydrophobic glucosylated photosensitizers
      mediated PDT (1, 3), compared to tetraphenylporphyrin (TPP). The lowest
      photosensitivity observed for TPP was consistent with the lowest uptake.
      Moreover, the most pronounced photodynamic activity measured for 3 was in
      relation with the improvement of cellular uptake, the singlet oxygen quantum
      yield and the high extinction coefficient value at 650 nm compared to porphyrins.
      Cellular localization analysis showed that 1 and 3 accumulated mainly inside the
      endoplasmic reticulum.

PMID- 15963606
TI  - Synthesis and inhibition of PGE2 production of 6,8-disubstituted chrysin
      derivatives.
AB  - A series of 6,8-disubstituted chrysin derivatives have been synthesized and
      evaluated for their PGE2 inhibitory activities. 6,8-Disubstituted chrysin
      derivatives were obtained from naturally occurring chrysin by halogenation,
      oxidation, thiomethylation and C-C cross coupling reaction. Among the compounds
      investigated, 6,8-dibromochrysin (2), 6,8-diiodochrysin (4), 6,8
      dimethylthiochrysin (9) and 6,8-dimethoxychrysin (11) showed as strong inhibitory
      activities of PGE2 production from LPS-induced RAW 264.7 cells as wogonin, a well
      known natural flavone having strong and selective COX-2 inhibitory activity.

PMID- 15963607
TI  - "Reference Biospheres" for solid radioactive waste disposal: the BIOMASS
      methodology.
AB  - The BIOMASS Theme 1 project has developed a methodology for the logical and
      defensible construction of 'assessment biospheres': mathematical representations
      of biospheres used in the total system performance assessment of radioactive
      waste disposal. The BIOMASS Methodology provides a systematic approach to
      decision making, including decisions on how to address biosphere change. The
      BIOMASS Methodology was developed through consultation and collaboration with
      many relevant organisations, including regulators, operators and a variety of
      independent experts. It has been developed to be practical and to be consistent
      with recommendations from ICRP and IAEA on radiation protection in the context of
      the disposal of long-lived solid radioactive wastes. The five main steps in the
      methodology are described in this paper. The importance of a clear assessment
      context, to clarify intentions and to support a coherent biosphere assessment
      process within an overall repository performance assessment, is strongly
      emphasised. A well described assessment context is an important tool for ensuring
      consistency across the performance assessment as a whole. The use of interaction
      matrices has been found to be helpful in clarifying the interactions between
      different habitats within the biosphere system and the significant radionuclide
      transfer pathways within the biosphere system. Matrices also provide a useful
      means of checking for consistency.

PMID- 15963608
TI  - Modelling and experimental studies on the transfer of radionuclides to fruit.
AB  - Although fruit is an important component of the diet, the extent to which it
      contributes to radiological exposure remains unclear, partially as a consequence
      of uncertainties in models and data used to assess transfer of radionuclides in
      the food chain. A Fruits Working Group operated as part of the IAEA BIOMASS
      (BIOsphere Modelling and ASSessment) programme from 1997 to 2000, with the aim of
      improving the robustness of the models that are used for radiological assessment.
      The Group completed a number of modelling and experimental activities including:
      (i) a review of experimental, field and modelling information on the transfer of
      radionuclides to fruit; (ii) discussion of recently completed or ongoing
      experimental studies; (iii) development of a database on the transfer of
      radionuclides to fruit; (iv) development of a conceptual model for fruit and (v)
      two model intercomparison studies and a model validation study. The Group
      achieved significant advances in understanding the processes involved in transfer
      of radionuclides to fruit. The work demonstrated that further experimental and
      modelling studies are required to ensure that the current generation of models
      can be applied to a wide range of scenarios.

PMID- 15963609
TI  - Does the Annane paper (2004) signal the end of HBO for ORN?

PMID- 15963611
TI  - Vascularisation of Norian CRS bone cement and its replacement by autologous bone
      when used for orbital reconstruction.
AB  - Various bone cements based on calcium phosphate have been used as adjuncts for
      repairing both the craniofacial and axial skeleton. Ideally these materials
      should provide initial strength and contour for the reconstruction, and be
      replaced over time by physiological absorption and bony deposition. Although
      there is evidence from animal models to support this, opportunities for human
      studies are rare. Here we offer clinical and histological evidence of this
      process.

PMID- 15963612
TI  - Design of monolimb using finite element modelling and statistics-based Taguchi
      method.
AB  - BACKGROUND: Monolimb is a transtibial prosthesis having the socket and shank
      molded into one piece of thermoplastic material. If properly designed, the shank
      of a monolimb can have a controlled deflection during walking which simulates the
      ankle joint motions to some extent. However, there is no clear guidance for the
      design of monolimb considering the dilemma between shank flexibility and
      structural integrity. METHODS: Finite element analysis was used to simulate
      structural tests based on ISO10328 on monolimbs of different configurations.
      Statistics-based Taguchi method was employed to identify the significance of each
      design factor in controlling the deformation and stress within monolimbs. The
      design factors considered were the thickness of the thermoplastics,
      anteroposterior and medialateral dimensions of the elliptical shank, and depth of
      the posterior seam line. By progressively fine-tuning the design factors, the
      monolimb configuration was optimized giving offering appropriate flexibilities of
      the shank and would not structurally fail in normal uses. Experimental structural
      test was used to validate the finite element model. FINDINGS: Anteroposterior
      dimension of the shank was shown to be the most important design factor
      determining the peak von Mises stress values, deformation and dorsiflexion angles
      of monolimbs. Depth of seam line appears much less important than the other three
      factors. A monolimb fulfilling the design requirements was suggested.
      Experimental test results reasonably matched with the finite element results.
      INTERPRETATION: Finite element analysis and Taguchi method was shown to be an
      effective method in optimizing the structural design of prostheses. Further
      prosthetic design can be facilitated based on the degree of importance of the
      design factors on the structural behavior of the prosthesis. Gait analysis of
      amputees using the suggested monolimb design is needed in the future.

PMID- 15963613
TI  - The cartilage thickness distribution in the tibiofemoral joint and its
      correlation with cartilage-to-cartilage contact.
AB  - OBJECTIVE: The objective of this study was to investigate whether regions of
      cartilage in the tibiofemoral joint where cartilage-to-cartilage contact occurred
      was thicker than other regions. DESIGN: In vivo human subjects. BACKGROUND: The
      thickness of the cartilage in the knee has been investigated in various studies.
      However, the factors that influence the thickness distribution within the joint
      remain unclear. METHODS: Six healthy living knees (5 male, 1 female, average age
      = 27) were scanned using magnetic resonance imaging. Three-dimensional models of
      the tibial and femoral cartilage layers were created. The cartilage thickness
      distribution was compared between regions where cartilage-to-cartilage contact
      was observed during in vivo weightbearing flexion and regions with no contact.
      RESULTS: The regions with cartilage-to-cartilage contact were significantly
      thicker than the regions without cartilage-to-cartilage contact (P < 0.05). On
      the medial condyle, the cartilage-to-cartilage contact regions were up to 40%
      thicker than regions with no contact. On the lateral femoral condyle, the maximum
      difference between these regions was 20%. On the tibial plateau, the maximal
      differences between regions with and without cartilage-to-cartilage contact were
      found to be 40% on the medial side and 50% on the lateral side. CONCLUSIONS: The
      data suggested that in normal knees, the cartilage was thicker in regions where
      cartilage-to-cartilage contact was present. Future studies should investigate the
      effects of in vivo loading on cartilage maintenance and growth. Relevance
      Injuries that alter knee kinematics might load regions of the joint where the
      cartilage is thinner. This might alter the stress distributions within the
      cartilage.

PMID- 15963614
TI  - An active shape model for the reconstruction of scoliotic deformities from back
      shape data.
AB  - OBJECTIVE: The objective of the present study is to improve the accuracy and
      reliability of the spinal midline reconstructions in scoliosis from back shape
      data. Design. An active shape model which covers the variety of scoliotic curves
      with a minimum of adjustable parameters is designed for the reconstruction of the
      spinal midline based on rasterstereographic back surface measurements.
      BACKGROUND: To reduce the number of X-rays needed for patients with a scoliosis,
      an automatic method was developed for the reconstruction of spinal deformities
      from back shape data. METHODS: 264 digital X-rays of 264 patients with scoliosis
      were used as a training set. By examining the statistics of the vertebral body
      centres a point distribution model was derived. The model is used as a basis to
      reconstruct the spinal midline from back shape data (active shape model).
      RESULTS: 478 rasterstereographs of 114 scoliotic patients have been evaluated
      with this new procedure and with an existing procedure. Both procedures deliver a
      three-dimensional curve of the spinal midline. The frontal projections of these
      spinal midlines are compared with the vertebral centres of the corresponding 478
      X-rays. The active shape model improved the results as compared to the existing
      procedure from sigma(x)=3.4mm to sigma(x)=3.0mm. CONCLUSION: The use of the
      active shape model improves the overall accuracy of the spinal midline
      reconstructions in scoliosis from back shape data.RELEVANCE. Improvements to the
      accuracy and the reliability of the three-dimensional spinal reconstruction based
      on back shape data, can lead to an additional reduction of X-rays for patients
      with a scoliosis.

PMID- 15963615
TI  - Comparison of zone II flexor tendon repairs using an in vitro linear cyclic
      testing protocol.
AB  - BACKGROUND: This study used in vitro cyclic testing protocol to examine the
      dynamic properties from a survivorship point of view for a modified Kessler core
      suture with a running epitenon suture, a modified Kessler core suture with a
      cross-stitched epitenon suture and a 4-strand Savage core suture with a running
      epitenon suture. METHODS: A survivorship analysis using in vitro dynamic
      mechanical testing was performed using 20 N and 33 N with 500 cycles to simulate
      early rehabilitation. The gap formation was recorded by direct measurement with
      an electronic calliper every 100 cycles at the point of lowest force during the
      cycle at the site of greatest gap formation. Results were analysed using a log
      rank test for survival analysis and the relative risk of deterioration
      calculated. FINDINGS: No significant increased risk of gap formation was noted
      for the Kessler with a cross-stitched epitenon over the standard Kessler repair.
      A significant decrease in the risk of significant gap formation in the Savage
      repair over the two Kessler repairs (>10-fold difference in the standard (P <
      0.01) and > 7-fold in the cross-stitched (P < 0.05) was found. INTERPRETATION:
      The survivorship testing protocol found the Savage repair to be superior to the
      other methods under dynamic loading. Survival curves and relative risks provide a
      unique way to assess the properties of different repair techniques.

PMID- 15963616
TI  - A comparative study between axial compression and lateral fall configuration
      tested in a rat proximal femur model.
AB  - BACKGROUND: Conventional testing method for evaluation of rat hip failure force
      is based on an axial compression approach. However, as the most osteoporotic hip
      fractures are a result of a lateral fall, it is necessary to establish mechanical
      testing methods more close to clinical conditions. This study was therefore
      designed to evaluate the differences in hip mechanical failure force to be tested
      between 'axial compression' and 'lateral fall configuration' in a rat proximal
      femur model. METHODS: Eighteen 10-month-old female Wistar rats were body-weight
      matched and divided into ovariectomized group (n = 9) and sham group (n = 9). All
      rats were euthanized 3 months after surgery. The bilateral proximal femora of
      each rat were excised. The left femur served for testing to failure in a fall
      configuration fashion while the right femur was tested using axial compression
      approach. After mechanical testing, the anterior-posterior radiographs were taken
      to identify the fracture mode and measure the Pauwel's angle between the fracture
      line and the line perpendicular to the femoral shaft long axis. FINDINGS: The
      failure force in fall configuration was significantly correlated with but lower
      than that tested in axial compression. A comparison between the ovariectomized
      and sham group showed that the failure force in both fall configuration and axial
      compression was found significantly higher in the sham group than that in the
      ovariectomized group. However, the logistic regression analysis revealed that the
      fall configuration approach had larger discrimination power. Radiographs showed
      that almost all samples fractured at the base of the femur neck. The Pauwel's
      angle in fall configuration group was significantly larger than that in axial
      compression group. INTERPRETATION: In comparison with the characteristics of
      axial compression test, the fall configuration approach generated higher shearing
      stress with larger bending moment to the bone and induced susceptibility to
      fracture at lower mechanical load. Although the failure force obtained from the
      two testing configurations revealed significant correlation, the mechanical
      testing in fall configuration demonstrated higher sensitivity in identifying the
      estrogen-deficiency induced deterioration of hip mechanical failure force as
      compared with that in axial compression. These findings suggested the potential
      application of lateral fall configuration in evaluation of improvement effects of
      intervention stratagems on hip mechanical failure force involving an
      ovariectomized rat model.

PMID- 15963617
TI  - Head and neck position sense in whiplash patients and healthy individuals and the
      effect of the cranio-cervical flexion action.
AB  - BACKGROUND: Whiplash may damage structures within the neck that can affect
      position sense. Deep neck flexor muscle retraining may improve position sense.
      The current study compared range of motion and position sense in whiplash and
      control subjects and investigated the effects of a muscle training session on
      position sense. METHODS: Twenty-three subjects with whiplash were compared with a
      matched control group. Range of motion and neck position sense measures were
      recorded using the 3-Space Fastrak. Measures of function were also assessed in
      the whiplash group. Subjects were then randomised into experimental and control
      groups and the former group received a training session to activate the deep neck
      flexor and scapular stabilising muscles (the cranio-cervical flexion action)
      during head and neck movements. After training, position sense measures were re
      evaluated. FINDINGS: Results showed significant reductions (P < 0.05) in active
      range of motion in the whiplash group when compared to the healthy group. No
      significant differences (P > 0.05) between whiplash and healthy groups in
      position matching accuracy were observed. Functional outcome scores indicated the
      whiplash group to be mildly disabled. No effect on error scores was observed when
      position-matching tasks were performed with and without the cranio-cervical
      flexion action. Correlations between functional measures or range of motion, and
      position sense were not significant. INTERPRETATION: There was no evidence of
      position sense impairment in the mildly disabled whiplash subjects. The
      performance of the cranio-cervical flexion action had no effect on position
      sense, and hence clinical improvements observed from using this action may be
      more associated with mechanical stabilisation.

PMID- 15963618
TI  - Income inequality, poverty, and population health: evidence from recent data for
      the United States.
AB  - In this study, state-level US data for the years 2000 and 1990 are used to
      provide additional evidence on the roles of income inequality and poverty in
      population health. Five main points are noted. First, contrary to the suggestion
      made in several recent studies, the income inequality parameter is observed to be
      quite robust and carries statistical significance in mortality equations
      estimated from several observation sets and a fairly wide variety of
      specificational choices. Second, the evidence does not indicate that significance
      of income inequality is lost when education variables are included. Third,
      similarly, the income inequality parameter shows significance when a race
      variable is added, and also when both race and urbanization terms are entered.
      Fourth, while poverty is seen to have some mortality-increasing consequence, the
      role of income inequality appears stronger. Fifth, income inequality retains
      statistical significance when a quadratic income term is added and also if the
      log-log version of a fairly inclusive model is estimated. I therefore suggest
      that the recent skepticism articulated by several scholars in regard to the
      robustness of the income inequality parameters in mortality equations estimated
      from the US data should be reconsidered.

PMID- 15963619
TI  - Handling of contamination variability in exposure assessment: a case study with
      ochratoxin A.
AB  - The contamination of foods dedicated to human consumption varies over space and
      time. In exposure assessment, this is usually addressed through probabilistic
      modelling. The present work explores how the variability and uncertainty of
      exposures estimated at the population level are affected by: (a) the (non
      )parametric nature of input contamination distributions; (b) the time-window used
      to sample contamination values within those distributions. Focusing on exposure
      of the French population to food mycotoxin ochratoxin A, we implement a range of
      second-order Monte-Carlo simulations that allow distinguishing variability of
      exposures from uncertainty of distributional parameters estimates. A simulation
      runs 10,000 iterations. Overall estimates of parameters are given by the median
      across iterations and 95%CI by 2.5th and 97.5th percentiles. Our results show
      that: (a) parametric (log-normal) input distributions may lead to over-estimation
      of variability and greater uncertainty as compared to non-parametric ones (P97.5
      [95%CI] of 7.1 [6.6;7.7] for Parametric-Occasion, 4.6 [4.3;5.0] for Non
      Parametric-Occasion), and that (b) the 'Occasion' time-window combines better
      estimate of variability and lower uncertainty when exposure modelling is applied
      to populations living in developed countries with complex agri-food systems
      (P97.5 [95%CI]: 7.3 [6.2;8.9] for Non-Parametric-Week, 4.6 [4.3;5.0] for Non
      Parametric-Occasion). A deterministic approach is nevertheless preferred to
      probabilistic modelling every time input data quality is questionable.

PMID- 15963620
TI  - Aptamers against extracellular targets for in vivo applications.
AB  - Oligonucleotides are multifunctional molecules which can interfere with gene
      expression by different mechanism such as antisense, RNA interference, ribozymes,
      etc. For most in vivo diagnostic and therapeutic applications, oligonucleotides
      need to be delivered to the intracellular compartment of a specific organ, a
      difficult task which limits considerably their use. However, aptamer
      oligonucleotides which target extracellular markers obviate this problem.
      Aptamers are short oligonucleotides (<100 bases) selected from large
      combinatorial pools of sequences for their capacity to bind to many types of
      different targets, ranging from small molecules (amino acids, antibiotics...) to
      proteins or nucleic acid structures. Aptamers present the same high specificity
      and affinity for their targets as antibodies. In addition to efficient binding,
      aptamers have been shown in many cases to display an inhibitory activity on their
      targets. Moreover, they seem to lack immunogenicity and can be chemically
      modified in order to improve their stability against nucleases or extend their
      blood circulation time, two properties which are particularly useful for in vivo
      applications. Recently, aptamers have been selected against whole living cells,
      opening a new avenue which presents three major advantages 1) direct selection
      without prior purification of the targets; 2) conservation of membrane proteins
      in their native conformation similar to the in vivo conditions and 3)
      identification of (new) targets for a specific phenotype. Many aptamers are now
      being developed against biomedical relevant extracellular targets: membrane
      receptor proteins, hormones, neuropeptides, coagulation factors... Among them,
      one aptamer that inhibits the human VEGF165 has recently been approved by FDA for
      the treatment of age-related macular degeneration. Here we discuss the recent
      developments of aptamers against extracellular targets for in vivo therapy and as
      tools for diagnosis using molecular imaging.

PMID- 15963621
TI  - Characterization of conformational epitope of alginate-derived polymannuronates
      by surface plasmon resonance.
AB  - In the present study, we developed a mAb to alginate-derived polymannuronates
      (ADPM) and examined the antigenic epitopes using surface plasmon resonance (SPR)
      in conjunction with a large panel of oligomannuronate probes. We found that
      tetrasaccharide is the minimum-binding unit, and that increases in chain length
      from the tetrasaccharide to the heptsaccharide further enhance monovalent
      binding. A sharp increase in affinity was observed when increasing from the
      octasaccharide to the cosasaccharide, which is due to a further enhancement of
      the individual antigenic epitope combined with multivalency. Kinetic binding
      studies further suggested that the conformational epitope is discontinuous and
      infrequent and that a C6-carboxyl group is important in maintaining the
      conformational epitope. Moreover, CD analysis revealed there were conformational
      structures in epitopes. The data support our hypothesis that the conformational
      epitope for the mAb may be an extended helical segment of ADPM. ADPM exists
      mainly in linear form, but it can infrequently and spontaneously form extended
      helices. Although helices are not prevalent in ADPM, the immune system
      preferentially selects these conformational epitopes because they are unique.
      Together, our results indicate that the antigenic epitopes in beta-d-mannuronates
      are conformational and require C6-carboxyl groups.

PMID- 15963622
TI  - Should there be a change in the teaching of airway management in the medical
      school curriculum?

PMID- 15963623
TI  - Methylenedioxymethamphetamine (ecstasy)-related myocardial hypertrophy: an
      autopsy study.
AB  - BACKGROUND: Myocardial hypertrophy is a well-recognized complication of cocaine
      and methamphetamine abuse and is a strong, independent risk factor for sudden
      death, myocardial infarction, and congestive heart failure. We sought to
      determine if use of MDMA (methylenedioxyamphetamine or "ecstasy") is associated
      with myocardial hypertrophy at death. METHODS AND RESULTS: A matched,
      retrospective study using medical examiner (ME) death reports. Consecutive MDMA
      positive (+) and MDMA negative (-) deaths identified from MEs in 10 states and a
      local county, respectively. Five MDMA(-) cases were matched to each MDMA(+) case
      for age, sex, and ethnicity. MDMA(+) cases were confirmed using GC/MS and other
      drugs of abuse (e.g., cocaine and methamphetamine) were absent. Matched MDMA(-)
      cases were trauma fatalities with intact hearts and blood negative for all
      illicit stimulants. Cardiac weights were compared between the two groups. Twenty
      seven MDMA(+) deaths and 135 matched MDMA(-) deaths were enrolled. Mean age was
      20 years (range 16--33 years); 44% were female. 70.4% were Caucasian, 14.8%
      African-American, 11.1% Asian, and 3.7% Hispanic. Mean heart weight of MDMA(+)
      fatalities was 315.7 and 277.2g for MDMA(-) fatalities (Diff=38.5 g; 95% CI=18.3-
      8.7). Multivariate analysis revealed that MDMA(+) fatalities were more likely to
      have an enlarged heart (OR=18.3; 95% CI=3.6--1.6). CONCLUSION: The findings of
      this study suggest that MDMA users might also be at risk for myocardial
      hypertrophy and possible cardiac toxicity, similar to other stimulants.

PMID- 15963624
TI  - Comparison of different kinds of probes used for analysis of variant telomeric
      sequences.
AB  - In this work we aimed to compare and critically evaluate results obtained by
      different types of probes used for hybridisation to detect variant telomeric
      sequences with respect to their reliability and information value. Using slot
      blot hybridisation we investigated three types of probes (oligonucleotides,
      cloned fragments and concatenated probes) under various conditions of
      hybridisation and washing. The concatenated probes exhibited the highest
      specificity although all three types are suitable for hybridisation of telomeric
      sequences under appropriate experimental conditions. We demonstrate how
      understanding generated from these data enables interpretation of hybridisation
      patterns of oligonucleotide probes to genomic DNAs.

PMID- 15963626
TI  - Specific molecular interactions by force spectroscopy: from single bonds to
      collective properties.
AB  - Interactions involving multiple bonds occur throughout biology, and have distinct
      properties that are fundamentally different from those present in single bond
      systems. We have developed a new method to analyse the AFM force measurements in
      order to extract relevant information and to characterise the interactions
      involving from single to multiple bonds. Our study reveals a surprising behaviour
      in the presence of multiple bonds with a high rebinding probability: the mean
      binding forces increase with decreasing pulling velocity. Such behaviour is
      different from the force dependence on the loading rate for single bond rupture
      or existing models for multiple bonds rupture.

PMID- 15963625
TI  - Why forces between proteins follow different Hofmeister series for pH above and
      below pI.
AB  - The relative effectiveness of different anions in crystallizing proteins follows
      a reversed Hofmeister sequence for pH<pI and a direct Hofmeister sequence for
      pH>pI. The phenomenon has been known almost since Hofmeister's original work but
      it has not been understood. It is here given a theoretical explanation. Classical
      electrolyte and double layer theory deals only with electrostatic forces acting
      between ions and proteins. Hydration and hydration interactions are dealt with
      usually only in terms of assumed hard core models. But there are, at and above
      biological salt concentrations, other non-electrostatic (NES) ion-specific forces
      acting that are ignored in such modeling. Such electrodynamic fluctuation forces
      are also responsible for ion-specific hydration. These missing forces are
      variously comprehended under familiar but generally unquantified terms,
      typically, hydration, hydrogen bonding, pi-electron-cation interactions, dipole
      dipole, dipole-induced dipole and induced dipole-induced dipole forces and so on.
      The many important body electrodynamic fluctuation force contributions are
      accessible from extensions of Lifshitz theory from which, with relevant
      dielectric susceptibility data on solutions as a function of frequency, the
      forces can be extracted quantitatively, at least in principle. The classical
      theories of colloid science that miss such contributions do not account for a
      whole variety of ion-specific phenomena. Numerical results that include these non
      electrostatic forces are given here for model calculations of the force between
      two model charge-regulated hen-egg-white protein surfaces. The surfaces are
      chosen to carry the same charge groups and charge density as the protein. What
      emerges is that for pH<pI (where the anions are counter-ions) the repulsive
      double layer forces increase in the order NaSCN<NaI<NaCl, while at higher pH>pI
      (where anions are co-ions) the forces increase in the order NaCl<NaI<NaSCN. This
      is in excellent agreement with both solubility experiments and experiments using
      SAXS. The results are also consistent with cation effects observed in protein
      solutions. Our results may provide some insights into a long-standing problem in
      solution chemistry and biology.

PMID- 15963627
TI  - Melting temperatures of nucleic acids: discrepancies in analysis.
AB  - Melting temperature, T(m), is an important property of nucleic acid duplexes. It
      is typically determined from spectroscopic or calorimetric melting experiments.
      More than one analytical method has been used to extract T(m) values from
      experimental melting data. Unfortunately, different methods do not give the same
      results; the same melting data can be assigned different T(m) values depending
      upon which method is used to process that data. Inconsistencies or systematic
      errors between T(m)s reported in published data sets can be significant and add
      confusion to the field. Errors introduced from analysis can be greater than
      experimental errors, ranging from a fraction of degree to several degrees. Of the
      various methods, the most consistent and meaningful approach defines melting
      temperature as the temperature at the transition midpoint where half of the base
      pairs are melted and standard free energy is zero. Assuming a two-state melting
      behavior, we present here a set of general equations that can be used to
      reconcile these analytical T(m) differences and convert results to the correct
      melting temperatures at the transition midpoint. Melting temperatures collected
      from published sources, which were analyzed using different methods, can now be
      corrected for these discrepancies and compared on equal footing. The similar
      corrections apply to T(m) differences between calorimetric and spectroscopic
      melting curves. New algorithm for selection of linear sloping baselines, 2nd
      derivative method, is suggested, which can be used to automate melting curve
      analysis.

PMID- 15963628
TI  - Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of
      transitional cell carcinoma of the urinary bladder.
AB  - OBJECTIVE: To assess whether urinary levels of tumor-associated trypsin inhibitor
      (TATI) would aid in the detection of bladder transitional cell carcinoma (TCC);
      and to compare diagnostic performance of urinary TATI with that of nuclear matrix
      protein 22 (NMP22) and barbotage cytology. METHODS: We determined TATI and NMP22
      levels in voided urine from 181 subjects: 153 with previous bladder cancer, 20
      with urologic pathology other than bladder cancer, and eight healthy volunteers.
      TATI was analyzed continuously and categorically on the basis of its quartile
      distribution. We also measured urinary creatinine and barbotage cytology in 173
      and 154 patients, respectively. RESULTS: Urinary TATI levels were significantly
      higher in TCC patients with evidence of tumor on cystoscopic evaluation (n = 96)
      than in control subjects (n = 85; p < 0.001). Higher levels of TATI were
      associated with positive cytology assay results (p = 0.018), higher NMP22 levels
      (p < 0.001), and invasive tumor stage (p = 0.026). The area under the receiver
      operating characteristics (ROC) curve (AUC) of TATI for the detection of TCC was
      0.712 (95%CI: 0.637-0.786). The overall AUCs for TATI and NMP22 were not
      statistically different from each other (p = 0.174). In the >75% sensitivity
      region of the ROC curves, TATI was consistently more specific than NMP22. TATI,
      NMP22, and cytology were independently associated with bladder cancer (p = 0.049,
      p = 0.040, and p < 0.001, respectively). Adjustment of TATI for urinary
      creatinine levels did not affect any of the outcomes. CONCLUSIONS: Urinary level
      of TATI may add independent information to urinary cytology and NMP22 in the
      detection of bladder TCC. TATI seems to outperform NMP22 for bladder TCC
      detection.

PMID- 15963629
TI  - Twenty years experience with semen cryopreservation in testicular cancer
      patients: who needs it?
AB  - PURPOSE: To evaluate the role of semen cryopreservation (SCP) in the fertility
      saving management of testicular cancer (TC) patients, treated at the Norwegian
      Radium Hospital between 1983 and 2002. PATIENTS AND METHODS: 422 of 1388 newly
      diagnosed TC patients had SCP All patients were followed up for post-treatment
      paternity. RESULTS: During the 20 years study period, by 2002 an increasing
      percentage of patients had pre-treatment SCP, reaching 43% after 1994. Twenty
      nine (7%) of the 422 patients with SCP had used their frozen semen for assisted
      reproductive techniques (ART) at least once to achieve fatherhood. Pregnancies
      were achieved in 16 of these patients' partners, but two of these pregnancies
      ended in abortions. 67(17%) of 393 men with SCP fathered at least one child
      without use of frozen semen. The comparable figures for those without SCP were
      205 out of 966(21%). Twenty years after orchiectomy the cumulative incidence of
      first post-treatment fatherhood was 47% for the 393 patients who had SCP but did
      not use it for ART, and 34% for the 966 patients without SCP (p=0.12).
      CONCLUSION: If offered, about 50% of the young and middle-aged patients newly
      diagnosed with TC are interested in pre-treatment SCP. Though our study reveals
      that a considerable number of TC patients referred to SCP, achieve fatherhood
      without the use of frozen semen, the psychological impact of pre-treatment
      cryopreservation is undeniable. Furthermore, for some TC survivors ART with
      cryopreserved sperm offers the only chance of post-treatment paternity.

PMID- 15963630
TI  - Telomere length on bladder washing samples from patients with bladder cancer
      correlates with tumor characteristics flow cytometry method for quantitative
      fluorescence in situ hybridization (flow-FISH technique).
AB  - OBJECTIVE: The purpose of the present study was to evaluate the length of
      telomeres in patients with bladder cancer using a quantitative flow cytometry
      (flow-FISH) technique. METHODS: Bladder washing samples from 51 patients with
      bladder cancer were obtained immediately before transurethral resection. The
      average length of telomere repeats was measured by flow-FISH, as previously
      reported. Results were expressed in molecular equivalents of soluble fluorochrome
      (MESF) units. RESULTS: Bladder washing specimens provided adequate cell numbers
      for flow-FISH in 49 cases. The TEL means were 1014.71, 2343.36, 5567 and 18267.57
      for Ta, T1, T2 and T3/4 tumors, respectively. Regarding grade it was obtained a
      mean MESF value of 1379.46, 3391.29 and 15925.11 for G1, G2 and G3, respectively.
      ANOVA demonstrated statistically significant differences in stage (p: 0.014) and
      tumor grades (p: 0.012). In relation to ploidy, we found a mean MESF value of
      2701.37 and 16085.44 MESF units for diploid and aneuploid cells, respectively.
      Significant difference (p: 0.003) was observed between both groups. CONCLUSION:
      To date, this is the first report wherein telomere length was measured using flow
      FISH method in exfoliated cells in urine from patients with bladder cancer.
      Further investigations are required to demonstrate whether flow-FISH technique
      might be considered as a tumor marker of bladder cancer.

PMID- 15963631
TI  - BCG dose reduction by decreasing the instillation frequency: effects on local
      Th1/Th2 cytokine responses in a mouse model.
AB  - OBJECTIVES: Based on the requirement of a Th1 immune response for clinical
      efficacy, and incited by the arbitrary induction scheme, frequent side effects
      and the empirical approach in improving BCG immunotherapy for superficial bladder
      cancer, an alternative intravesical BCG treatment schedule for dose reduction was
      investigated without compromising Th1 cytokine induction in the bladder in a
      mouse model. METHODS: Mice were submitted to 6 weekly BCG instillations and
      treatment schedules omitting intermediate instillations during this standard
      scheme. Th1 (IFN-gamma, IL-2, IL-12p40), and Th2 (IL-10, IL-4) cytokine responses
      in individual mouse bladders were measured by a semiquantitative RT-PCR based
      method. RESULTS: A schedule of only two BCG instillations, administered in week 1
      and week 6, resulted in induction of at least the same levels of IFN-gamma, IL-2
      and IL-12p40 Th1 cytokine mRNA compared to 6 weekly instillations, whereas
      significantly lower levels of Th2 cytokines IL-10 and IL-4 mRNA were observed.
      CONCLUSIONS: During the 6-week period the intermediate weekly BCG instillations
      2, 3, 4, and 5 do not contribute to Th1 cytokine upregulation in the bladder,
      provided that the BCG dose is sufficient. Whether such a reduced BCG frequency
      schedule has immune stimulating capacity and therapeutic efficacy associated with
      less side effects in patients remains to be investigated.

PMID- 15963632
TI  - A role for the P2X receptor in urinary tract physiology and in the
      pathophysiology of urinary dysfunction.
AB  - OBJECTIVE: We provide a historical perspective of the P2X receptor class in
      bladder physiology and the pathophysiology of urinary dysfunction. METHODS: A
      literature search was performed using the MEDLINE database. RESULTS: Evidence
      suggests that P2X receptors serve a combined function in sensory and motor
      activity of human bladder. P2X receptors mediate excitation of sensory neurons
      and evoke muscle contraction in response to ATP release. Anatomical and
      functional defects in the P2X receptor signaling are associated with a variety of
      urologic diseases. CONCLUSION: Current research underscores the importance of P2X
      receptors in urologic physiology. Potential applications exist in relation to the
      diagnosis and treatment of urinary dysfunction. However, the detailed mechanism
      of P2X receptor function in bladder physiology and in urinary tract disease
      remains unknown and warrants further investigation.

PMID- 15963633
TI  - Female urinary incontinence in the west of Turkey: prevalence, risk factors and
      impact on quality of life.
AB  - OBJECTIVES: To determine the prevalence and risk factors of urinary incontinence
      (UI), and to assess its impact on quality of life (QOL) in Turkish women.
      METHODS: In this cross-sectional study, 1012 women aged over 18 years were
      interviewed through a questionnaire including 'International Consultation on
      Incontinence Questionnaire Short Form'. RESULTS: The overall prevalence of UI was
      23.9% (n=242). Among these women, 62 (25.6%) had urge, 80 (33.1%) stress and 100
      (41.3%) mixed type UI. The prevalence rate increased with advancing age. Eighty
      nine women (36.8%) stated to have urinary leakage at least once a day or more,
      while 153 (63.2%) women were experiencing less than twice a week. UI was
      significantly associated with fecal incontinence, hypertension, history of
      nocturnal enuresis, and recurrent urinary tract infections. Overall, 211 (87.2%)
      women stated that UI have negative impact on the QOL. This effect remained mostly
      at the mild or moderate level. Although many (87.2%) had intention for medical
      assistance, only a few (14.9%) had realized it. Women with urge UI and aged 40 to
      50 years looked for more assistance than others. CONCLUSIONS: UI affect
      approximately one of four Turkish women. The results emphasize the need for
      taking preventive measures and policy development for UI.

PMID- 15963634
TI  - The impact of prostate size in laparoscopic radical prostatectomy.
AB  - OBJECTIVES: Large prostates can be challenging to remove during open or
      laparoscopic radical prostatectomy (LRP). Our objective was to critically analyse
      the impact of prostate volume in LRP. METHODS: 400 cases of LRP were performed.
      Three hundred and fourteen patients had a small prostate (weight < 75 g) and 86
      patients had a large prostate (weight > or = 75 g) on final histology. The
      following outcomes were assessed: operative time; estimated blood loss (EBL);
      transfusion rate; length of hospital stay (LOS); length of catheterisation;
      perioperative and postoperative complications (including incontinence and
      erectile dysfunction); surgical margin status; and early biochemical recurrence
      rates. RESULTS: Patients' age, PSA, Gleason sum and clinical stage were all
      similar. Larger prostates were associated with a 14 minutes longer mean operating
      time (p < 0.001), but fewer positive surgical margins (p = 0.01). Blood loss,
      blood transfusion rate, length of hospital stay, length of catheterisation and
      complication rate were all similar in both groups. CONCLUSIONS: Prostate size
      should not be a factor determining a patient's suitability for LRP. Further
      follow-up is needed to assess the effect of prostate size on long-term functional
      and oncological results.

PMID- 15963635
TI  - Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic
      significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and
      BCG-non-treated patients.
AB  - OBJECTIVES: This study aimed to determine the prognostic value of depth of lamina
      propria invasion in initial high-grade T1 bladder tumors. Secondary aims were to
      evaluate the prognostic significance of concomitant carcinoma in situ (CIS) and
      the impact of bacillus Calmette-Guerin (BCG) treatment as well as to assess the
      feasibility of microstaging by pathologists in a community setting. PATIENTS AND
      METHODS: Ninety-seven tumors were available for study and were substaged
      according to invasion superficial to, into or beyond the muscularis mucosae (MM)
      (T1a, T1b, T1c). Outcomes were compared by chi-square analysis. Recurrence-free
      and progression-free survival estimates were obtained by Kaplan-Meier analysis.
      BCG treatment impact and prognostic significance of CIS were also evaluated (Cox
      regression). RESULTS: T1 subclassification was possible in 87% (85/97) of cases:
      38 (39.1%) T1a, 10 (10.3%) T1b, and 37 (38.1%) T1c; in 12 patients (12.4%)
      substaging was not possible. Mean age was 66.4 years and mean follow-up was 53
      months. Recurrence rates were similar for all groups. By contrast, the
      progression rate for deep lamina propria-invasive tumors, i.e. T1b and T1c, was
      34% (16/47) in comparison to 8% (3/38) for T1a (p=0.016). Progression-free
      intervals were significantly different in patients with (T1b, T1c) or without
      (T1a) deep lamina propria involvement (p=0.003), regardless of BCG treatment
      (p=0.02). BCG-treated patients (67 cases) showed a slight trend towards a better
      outcome, but differences were not significant. CIS was associated with more than
      50% of cases that progressed. On multivariate analysis, depth of invasion and CIS
      remained two independent prognostic factors, increasing the hazards ratio of
      progression to 4.47 and 3.19 respectively. CONCLUSIONS: The depth of invasion in
      the TURB specimens is an independent prognostic factor for T1 bladder cancer even
      in BCG-treated patients. Associated CIS significantly increases the risk of
      progression in these patients. The percentage of cases that can be substaged
      according to the depth of lamina propria involvement increases over time with the
      collaboration between urologists and pathologists. Consequently, we support that
      routine pathological assessment of the level of MM invasion in patients with
      stage T1 bladder cancer should be included in the histopathological report.

PMID- 15963636
TI  - Phase II trial of weekly paclitaxel and carboplatin chemotherapy in patients with
      advanced transitional cell cancer.
AB  - OBJECTIVE: We investigated the efficacy and toxicity of a first-line combination
      chemotherapy using weekly paclitaxel and carboplatin in patients with metastatic
      transitional cell cancer (TCC). PATIENTS AND METHODS: Thirty-three patients with
      advanced measurable TCC of the urothelium were entered onto this trial. Patients
      were treated once weekly with a combination therapy of paclitaxel (100mg/m(2))
      and carboplatin (AUC 2, according to the Calvert formula). Therapy courses were
      administered for six consecutive weeks. After two cycles, a re-staging was
      carried out to evaluate response. RESULTS: Objective response rate was 57.6% with
      6 complete (18.2%) and 13 partial remissions (39.4%). Seven patients had stable
      disease (21.2%) and 7 patients had progressed at the first evaluation of response
      (21.2%). Median progression-free interval and median survival was 6.5 (1-35) and
      12 (2.5-58) months, respectively. Toxicity was moderate and manageable with grade
      3 and 4 neutropenia in 8 patients (24%), but no case of neutropenic fever. Other
      hematological grade 3 toxicities occurred in 9 patients (27%) and grade 3
      peripheral neuropathy in 2 patients (6%). There was no treatment-related death.
      Dose reduction or short delay of treatment was necessary in 3 patients.
      CONCLUSIONS: Combination therapy using weekly paclitaxel and carboplatin was
      active in patients with advanced TCC and adverse prognostic features. The weekly
      dosing used in this trial warrants further investigation as an alternative first
      line approach in patients with poor renal reserve and/or performance status or as
      a second-line management of advanced TCC.

PMID- 15963637
TI  - HGF and postnatal testis development.
AB  - Hepatocyte growth factor regulates many cellular functions acting through c-met,
      its specific receptor with tyrosine kinase activity. We have previously reported
      that in prepubertal rats HGF is secreted in the seminiferous tubules by purified
      peritubular myoid cells whereas Sertoli cells do not express HGF mRNA. In the
      present paper we report that HGF is expressed by the myoid cells during the
      entire postnatal testicular development studied and secreted in the culture
      medium. On the contrary, in Sertoli cells HGF starts to be clearly detectable by
      northern blot at 25 days of age. HGF is expressed and secreted by Sertoli cells
      isolated from 35-day-old rats and is able to increase the levels of c-met
      expression of the Sertoli cells. Although the role of HGF during the development
      of the postnatal testis need further research to be clarified, the data here
      presented indicate that HGF is one of the growth factors regulating mammalian
      testicular function.

PMID- 15963638
TI  - Concomitant choroid plexus papillomas involving the third and fourth ventricles:
      A case report and review of the literature.
AB  - Choroid plexus papillomas (CPP) are histopathologically benign and rare central
      nervous system (CNS) neoplasms arising from the epithelium of the choroid plexus.
      The most common site of presentation of these lesions is in the fourth ventricle
      in adults and lateral ventricles in children. Third ventricular CPP are uncommon.
      In this study, we present a case of a 66-year-old woman with complaints of
      progressive confusion, lethargy, and weakness who was found to have concomitant
      third and fourth ventricular masses on imaging studies. The patient underwent a
      biopsy of the third ventricular mass. The biopsy was followed by staged
      resections of the fourth and third ventricular masses, respectively. Pathology
      from the biopsy and both resections was benign CPP. Multifocal concomitant CPP is
      rare. Concomitant CPPs may be secondary to mere coincidental tumor occurrence or
      to biologic seeding of cerebrospinal fluid (CSF) from a primary CPP despite
      otherwise benign histopathology. The primary treatment for CPP is surgical
      resection. Post-operative chemotherapy or radiation for CPP is of controversial
      benefit.

PMID- 15963639
TI  - Bilateral C5 motor paralysis following anterior cervical surgery--a case report.
AB  - Numerous authors have reported C5 root palsies following posterior cervical
      surgery, and several mechanisms of injury have been proposed. Similar deficits
      after anterior cervical procedures are considered to occur less commonly. We
      report on a 48-year-old male who underwent multi-level anterior discectomy and
      fusion for cervical spondylotic myelopathy. Bilateral C5 nerve root deficits were
      noticed in the immediate postoperative period, and treated non-operatively. A
      postoperative magnetic resonance imaging (MRI) scan showed an increase in
      cervical lordosis accompanied by a posterior shifting of the spinal cord.
      Potential mechanisms of nerve root injury in this situation are discussed, and
      the literature on postoperative C5 root deficits is reviewed. The patient
      returned to his preoperative occupation as an operating room nurse 6 months
      following surgery, with complete neurologic recovery occurring over an 11-month
      period. C5 deficits following anterior cervical surgery occur more frequently
      than generally assumed. Improved lordosis and longitudinal lengthening of the
      cervical spinal column in multilevel anterior decompression and interbody fusion
      can paradoxically result in a traction injury to the spinal cord and C5 nerve
      roots.

PMID- 15963640
TI  - 14-3-3Zeta does not increase GSK3beta-mediated tau phosphorylation in cell
      culture models.
AB  - Tau is a neuronal microtubule-associated protein whose function is regulated by
      site-specific phosphorylation. One protein kinase that is likely to play an
      important role in regulating the phosphorylation state of tau in vivo is glycogen
      synthase kinase (GSK) 3beta. The activity of GSK3beta is regulated by specific
      protein-protein interactions and 14-3-3zeta, a member of a protein family that
      can act as scaffolds, was recently reported to co-purify with GSK3beta in a large
      protein complex that was isolated from bovine brain [A. Agarwal-Mawal, H.Y.
      Qureshi, P.W. Cafferty, Z. Yuan, D. Han, R. Lin, H.K. Paudel, 14-3-3 connects
      glycogen synthase kinase-3 beta to tau within a brain microtubule-associated tau
      phosphorylation complex, J. Biol. Chem. 278 (2003) 12722-12728]. The purpose of
      this study was to determine if 14-3-3zeta could act as a scaffolding protein to
      promote the interaction of GSK3beta with tau and subsequently, enhance GSK3beta
      mediated tau hyperphosphorylation. We used cell culture models,
      immunoprecipitation, and Western blotting to examine the interaction of GSK3beta
      and 14-3-3zeta with both exogenously and endogenously expressed proteins. We
      found that GSK3beta, 14-3-3zeta and tau do not interact in these cellular models
      under our experimental conditions and that GSK3beta-mediated tau phosphorylation
      is not effected by the presence of 14-3-3zeta. These data indicate that 14-3
      3zeta may not be directly interacting with GSK3beta and tau in the brain, but may
      indirectly facilitate the interactions by binding to other proteins.

PMID- 15963642
TI  - Chemical analysis of nanometric dielectric layers using spatially resolved VEELS.
AB  - Chemical analysis of structures in the nanometre range is a challenge even with
      modern analytical transmission electron microscopes (TEM). In this work we
      demonstrate that it is possible to measure chemical variations in the monolayer
      scale and identify compounds formed at the interfaces by using Valence Electron
      Energy Loss Spectroscopy (VEELS) in STEM line-scan mode. We discuss the impact of
      valence electrons delocalisation on the spatial resolution of our experiments.
      The method is tested first on a model sample containing a 4 nm HfO(2) layer. The
      limitations of VEELS to provide chemical analysis are then explored and discussed
      by applying this technique to a real semiconductor device containing a 2 nm
      HfO(2) layer.

PMID- 15963641
TI  - Insect-vertebrate chimeric nicotinic acetylcholine receptors identify a region,
      loop B to the N-terminus of the Drosophila Dalpha2 subunit, which contributes to
      neonicotinoid sensitivity.
AB  - A chimera based on the chicken alpha4 nicotinic acetylcholine receptor (nAChR)
      subunit containing an insert from loop B to the N-terminus of the Drosophila
      melanogaster Dalpha2 (=SAD) subunit was constructed and co-expressed with the
      chicken beta2 nAChR subunit in Xenopus laevis oocytes. The actions of the
      neonicotinoid insecticide imidacloprid were examined. Replacement of the region
      loop B to the N-terminus of the alpha4 subunit by the corresponding region of the
      Dalpha2 subunit had little effect on the concentration-response curve for
      imidacloprid. However, replacement of Glu219 by proline in the YXCC motif in loop
      C of the chimeric alpha4 subunit resulted in a marked displacement to the left of
      the concentration-response curve for imidacloprid not seen when an equivalent
      mutation was made in the alpha4beta2 nAChR. The results suggest that the region
      loop B to the N-terminus in the Dalpha2 subunit contributes to the high
      imidacloprid sensitivity of the hybrid Dalpha2beta2 nAChR.

PMID- 15963643
TI  - Internal cavities and ligand passageways in human hemoglobin characterized by
      molecular dynamics simulations.
AB  - Molecular dynamics simulations of the unliganded T state of human hemoglobin
      showed the existence of a spontaneous, very wide cavity on the distal side of the
      alpha subunit. This cavity consists of three tunnels spreading from the vicinity
      of the iron atom (the ligand binding site) to the surface of the subunit,
      constituting possible passageways for the entrance of the ligand. A fourth
      passageway was characterized due to the trajectory of water molecules entering or
      leaving the heme pocket. Analogous passages were observed in the beta subunits.
      They all appear and disappear dynamically, although some parts of them are more
      persistent along the trajectories. The most persistent regions within these
      tunnels correspond to all the xenon docking sites of human cytoglobin and to some
      of those of sperm whale and horse heart myoglobins and group I truncated
      hemoglobins.

PMID- 15963644
TI  - Protective effect of trapidil against oxidative organ damage in burn injury.
AB  - Animal models of thermal injury indicate reactive oxygen species and inflammatory
      cytokines as causative agents in tissue injury on various organs distant from the
      original wound. Trapidil has various properties, such as inhibition of platelet
      aggregation and lipid peroxidation as well as reduction of the inflammatory
      response to injury. This study was designed to determine the possible protective
      effect of trapidil treatment against oxidative organ damage in lung, intestine
      and kidney induced by cutaneous thermal injury. Thirty Wistar rats were randomly
      divided into five groups. Sham group (n=6) was exposed to 21 degrees C water
      while burn-3 h group (n=6) and burn+trap-3h group (n=6), burn-24 h (n=6) and
      burn+trap-24 h groups were exposed to boiling water for 12s to produce a full
      thickness burn in 35-40% of total body surface area. In both burn+trap-3 h and
      burn-trap-24 h group, 8 mg/kg trapidil was given intravenously immediately after
      thermal injury. Three and 24 h later, tissue samples were taken for biochemical
      analysis from lung, intestine and kidney and blood samples were obtained to
      determinate serum TNF-alpha levels. Cutaneous thermal injury caused a significant
      increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) and 3
      nitrotyrozine (3-NT) levels in all tissues and elevated serum TNF-alpha levels at
      post-burn 3 and 24 h. Trapidil treatment significantly reduced in biochemical
      parameters, as well as serum TNF-alpha levels. These data suggest that trapidil
      has a protective effect against oxidative organ damage in burn injury.

PMID- 15963645
TI  - A classified approach to burn contractures.

PMID- 15963646
TI  - Angiotensin type 1 receptor blockage improves ischemic injury following transient
      focal cerebral ischemia.
AB  - Following cerebral ischemia, i.v. infusion of angiotensin II increases cerebral
      edema and mortality. Angiotensin type 1 receptor blockage should therefore
      improve acute cerebral ischemia. Left middle cerebral artery occlusion (120 min)
      followed by reperfusion was performed with the thread method under halothane
      anesthesia in Sprague-Dawley rats. Olmesartan (angiotensin type 1 receptor
      blocker; 0.01 or 0.1mumol/kg/h) was infused i.p. for 7 days following middle
      cerebral artery occlusion followed by reperfusion. Stroke index score, infarct
      volume, specific gravity, and brain angiotensin II and matrix metalloproteinases
      were quantified in the ischemic and non-ischemic hemispheres. Olmesartan
      treatment improved stroke index score, infarct volume, and cerebral edema in our
      cerebral ischemia model. In particular, stroke index score, infarct volume, and
      cerebral edema were reduced even with a low dose of olmesartan that did not
      decrease blood pressure. Paralleling these effects on cerebral ischemia,
      olmesartan treatment also reduced the reactive upregulation in brain angiotensin
      II, matrix metalloproteinase-2, matrix metalloproteinase-9, and membrane type 1
      matrix metalloproteinase in the ischemic area. Angiotensin type 1 receptor
      stimulation may be one of the important factors that cause cerebral edema
      following cerebral ischemia, and that its inhibition may be of therapeutic
      advantage in cerebral ischemia.

PMID- 15963647
TI  - Endogenous release and multiple actions of secretin in the rat cerebellum.
AB  - Previous studies demonstrated that secretin could modulate synaptic transmission
      in the rat cerebellum. In the present report, we provide evidence for the
      endogenous release of secretin in the cerebellum and further characterize the
      actions of secretin in this brain area. First, to show that secretin is released
      endogenously, blocks of freshly dissected cerebella were challenged with a high
      concentration of KCl. Incubation with KCl almost doubled the rate of secretin
      release. This KCl-induced release was sensitive to tetrodotoxin and cadmium
      suggesting the involvement of voltage-gated sodium and calcium channels. The use
      of specific channel blockers further revealed that L-type and P/Q-type calcium
      channels underlie both basal and KCl-evoked secretin release. In support of this,
      depolarization of Purkinje neurons in the presence of NMDA, group II mGluR and
      cannabinoid CB1 receptor blockers resulted in increased inhibitory postsynaptic
      current frequency. Second, we found that the previously reported facilitatory
      action of secretin on GABAergic inputs to Purkinje neurons is partly dependent on
      the release of endogenous glutamate. In the presence of CNQX, an AMPA/kainate
      receptor antagonist, the facilitatory effect of secretin on GABA release was
      significantly reduced. In support of this idea, application of AMPA, but not
      kainate receptor agonist, facilitated GABA release from inhibitory terminals, an
      action that was sensitive to AMPA receptor antagonists. These data indicate that
      a direct and an indirect pathway mediate the action of secretin in the basket
      cell-Purkinje neuron synapse. The results provide further and more solid evidence
      for the role of secretin as a neuropeptide in the mammalian CNS.

PMID- 15963648
TI  - Synergistic effects of the peptide fragment D-NAPVSIPQ on ethanol inhibition of
      synaptic plasticity and NMDA receptors in rat hippocampus.
AB  - The L1 cell adhesion molecule has been implicated in ethanol teratogenesis as
      well as NMDAR-dependent long-term potentiation (LTP) of synaptic transmission, a
      process thought to be critical for neural development. Ethanol inhibits LTP at
      least in part by interacting with NMDA receptors. Ethanol also inhibits L1
      mediated cell adhesion in a manner that is prevented by an octapeptide, D
      NAPVSIPQ (D-NAP), as well as long chain alcohols such as 1-octanol. Here we
      analyzed the effects of D-NAP and 1-octanol on ethanol modulation of LTP induced
      by theta burst stimulation in two subfields of the rat hippocampus, the dentate
      gyrus and area CA1. When theta burst stimulation was delivered in ethanol (50
      mM), LTP was inhibited by about 50%. Surprisingly, when D-NAP (10(-7) M) and
      ethanol were co-applied or applied sequentially, LTP was completely absent. The
      effects of D-NAP were persistent, since delivery of a second theta burst
      stimulation following washout of D-NAP and ethanol elicited minimal plasticity.
      Application of D-NAP alone had no effect on LTP induction or expression. The
      synergistic effect of D-NAP on ethanol inhibition of LTP was concentration
      dependent since D-NAP (10(-10) M) had an intermediate effect, while D-NAP (10(
      13) M) had no effect on ethanol suppression of LTP. These observations were also
      replicated with a different ethanol antagonist, 1-octanol, in area CA1. To
      address the mechanisms underlying this long-lasting suppression of LTP, the
      sensitivity of pharmacologically isolated NMDAR extracellular field potentials to
      combinations of D-NAP and ethanol was determined. D-NAP (10(-7)M) alone had no
      effect on NMDA extracellular field potentials; however, the peptide significantly
      increased the inhibitory action of ethanol on NMDA extracellular field potential.
      The findings suggest that D-NAP and 1-octanol selectively interact with NMDA
      receptors in an ethanol-dependent manner, further implicating the L1 cell
      adhesion molecule in alcohol-related brain disorders.

PMID- 15963649
TI  - Somatic Ca(2+) dynamics in response to choline-mediated excitation in
      histaminergic tuberomammillary neurons.
AB  - Histaminergic tuberomammillary (TM) neurons of the posterior hypothalamus have
      been implicated in cognition, alertness and sleep-wakefulness cycles. Spontaneous
      firing of TM neurons has been associated with histamine release and wakefulness.
      The expression of alpha7 nicotinic acetylcholine receptors (nAChRs) in TM neurons
      suggests a role for endogenous choline and for nicotinic drugs in the regulation
      of intracellular Ca(2+) metabolism, normal TM neuronal activity and histamine
      release. First, we established the link between TM neuronal spontaneous firing
      frequency and cytosolic free Ca(2+) concentration ([Ca(2+)](i)). A strong
      correlation was observed: an onset of spontaneous firing (3-4Hz) was accompanied
      by a 20-fold increase in [Ca(2+)](i) from 56+/-18 nM to 1.0+/-0.6 microM. The
      same range of firing frequencies has been observed in TM neurons in vivo and is
      associated with wakefulness. Secondly, choline-induced activation of alpha7
      nAChRs did not elevate [Ca(2+)](i) directly, i.e. in the absence of high
      threshold voltage-gated Ca(2+) channel (HVGCC) activation. Cd(2+) (200 microM)
      completely blocked all Ca(2+) signals, but inhibited only 37+/-16% of alpha7
      nAChR-mediated currents. Thirdly, the responsiveness of [Ca(2+)](i) to choline
      mediated excitation was inhibited by hyperpolarization and enhanced by
      depolarization, sensitizing [Ca(2+)](i) at membrane voltages associated with
      normal TM neuronal activity. These properties of [Ca(2+)](i) define the ability
      of TM neurons to translate cholinergic stimuli of identical strengths into
      different cytosolic Ca(2+) effects, providing the physiological substrate for
      state-specific modulation of incoming cholinergic information and would be
      expected to play a very important role in determining activity profiles of TM
      neurons exposed to elevated concentrations of cholinergic agents, such as choline
      and nicotine.

PMID- 15963650
TI  - The role of the amygdala in human fear: automatic detection of threat.
AB  - Behavioral data suggest that fear stimuli automatically activate fear and capture
      attention. This effect is likely to be mediated by a subcortical brain network
      centered on the amygdala. Consistent with this view, brain imaging studies show
      that masked facial stimuli activate the amygdala as do masked pictures of
      threatening animals such as snakes and spiders. When the stimulus conditions
      allow conscious processing, the amygdala response to feared stimuli is enhanced
      and a cortical network that includes the anterior cingulate cortex and the
      anterior insula is activated. However, the initial amygdala response to a fear
      relevant but non-feared stimulus (e.g. pictures of spiders for a snake phobic)
      disappears with conscious processing and the cortical network is not recruited.
      Instead there is activation of the dorsolateral and orbitofrontal cortices that
      appears to inhibit the amygdala response. The data suggest that activation of the
      amygdala is mediated by a subcortical pathway, which passes through the superior
      colliculi and the pulvinar nucleus of the thalamus before accessing the amygdala,
      and which operates on low spatial frequency information.

PMID- 15963651
TI  - Coping with critical life events and lack of control--the exertion of control.
AB  - Coping strategies in relation to unfair treatment or conflicts at work are
      discussed. 'Covert coping' has been assessed by means of a short questionnaire.
      Its relationship with cardiovascular risk and sick leave has been examined in an
      epidemiological study (WOLF) of working men and women in Stockholm. The findings
      indicate that in men 'covert coping' is associated with elevated cardiovascular
      risk and prospective long-term sick leave. In women such a coping strategy is
      related to current sick leave, but not to cardiovascular risk or long-term sick
      leave. Openness of coping strategies is also discussed in relation to bouts of
      anger preceding myocardial infarction. Another epidemiological study (SHEEP,
      ONSET) has shown that severe bouts of anger are reported significantly more often
      than expected during the hour preceding myocardial infarction. This was not the
      case in subjects who reported 'open coping patterns', however. Openness of coping
      strategies is partly determined by the working climate--the higher the decision
      latitude, the less 'covert' the coping strategies. The results support the idea
      that dialogue in the work place may be health promoting.

PMID- 15963652
TI  - Stress hormones in health and illness: the roles of work and gender.
AB  - Two neuroendocrine systems are of specific interest in the study of stress and
      health; the sympathetic adrenomedullary system with the secretion of epinephrine
      and norepinephrine, and the hypothalamic pituitary adrenocortical (HPA) system
      with the secretion of cortisol. These hormones have often been used as objective
      indicators of stress in the individual. However, through their bodily effects,
      they are also a link between the psychosocial environment and various health
      outcomes. From a series of studies of women and men, it was concluded that gender
      roles and psychological factors are more important than biological factors for
      the sex differences in stress responses. The stress responses have been important
      for human and animal survival and for protection of the body. However, in modern
      society, some of these bodily responses may cause harm rather than protection.
      The catecholamines have been linked to cardiovascular disorders such as
      hypertension, myocardial infarction and stroke, cortisol to cardiovascular
      disease, Type 2 diabetes, reduced immune function and cognitive impairment. An
      adequate balance between catabolic (mobilization of energy) and anabolic
      processes (growth, healing) is considered necessary for long term health and
      survival. In modern society, which is characterized by a rapid pace of life, high
      demands, efficiency and competitiveness in a global economy, it is likely that
      lack of rest, recovery and restitution is a greater health problem than the
      absolute level of stress.

PMID- 15963653
TI  - Biological sensitisation and psychological amplification: gateways to subjective
      health complaints and somatoform disorders.
AB  - Subjective health complaints without known physical pathology are common and
      might develop into somatoform disorders. Normalization of neuroticism and anxiety
      in patients with duodenal ulcer disease after a relapse-free state is acquired
      and maintained is an indication that biological factors influence psychological
      factors. Recent research has shown that psychological and behavioural changes, on
      the other hand, have the capacity to change the brain. Visceral hyperalgesia is
      an example of biological sensitisation, but the abnormal sensory perception can
      be normalised by hypnotherapy. The dual-etiology hypothesis of functional somatic
      syndromes implies that in some patients with somatoform disorders there is a
      predominant biological etiology, whereas in others there is a predominant
      psychological etiology. The theory is supported by recent research, and may
      result in better handling of patients. Cognitive factors like catastrofising
      amplifies subjective physical symptoms and emotions effect the perception of
      them. In preventive health care the following slogans are proposed as antidotes
      preventing subjective health complaints form developing into somatoform
      disorders: Do not listen to your body's signals! Do not trust your feelings! Do
      not trust your thoughts!

PMID- 15963654
TI  - Trauma and resulting sensitization effects are modulated by psychological
      factors.
AB  - Traumas have both immediate consequences and proactive consequences. Examples
      include learned helplessness, HPA-axis responsivity, gastrointestinal
      vulnerability to ulcer, and other correlates of anxiety disorders. Both immediate
      and proactive consequences may be modulated by behavioral and cognitive
      evolutionary evolved adaption processes, among which are forms of learning that
      enable 'coping'. Examples of associative and non-associative forms of coping and
      effects on learned helplessness, HPA-axis responsivity, and gastrointestinal
      vulnerability are presented. The importance of attention to behavioral
      contingencies in situations in which potentially traumatic events occur is
      emphasized as critical to understanding that it is not the physical event(s) per
      se that determine the immediate and long term consequences.

PMID- 15963655
TI  - Long-term potentiation in spinal nociceptive systems--how acute pain may become
      chronic.
AB  - Chronic pain is a major problem since it is difficult to treat and the
      understanding of the underlying neurobiology is sparse. The mechanisms
      underpinning the transition of acute into chronic pain remain unclear. However,
      long-term potentiation (LTP) in spinal nociceptive systems may be one such
      mechanism. Here, we briefly review the literature regarding LTP in spinal
      nociceptive systems including our own data on LTP in deep convergent nociceptive
      neurons. Furthermore, we discuss the role of this phenomenon in understanding the
      neurobiology of chronic pain and the possible therapeutic implications.

PMID- 15963656
TI  - Lipoxin biosynthesis mediated by purine-/pyrimidine-(P2) receptor(s) signaling: a
      rationale for a novel mechanism.

PMID- 15963657
TI  - Fascioscapulohumeral muscular dystrophy: a progressive degenerative disease that
      responds to diltiazem.
AB  - The authors believe that with fascioscapulohumeral muscular dystrophy (FSHD),
      like Duchenne muscular dystrophy, there is Ca2+ dysregulation in the muscle
      cells. The dysregulated Ca2+ can cause cell death in various ways. One mechanism
      may be Ca2+ triggering abnormal levels of tumor necrosis factor (TNF-alpha).
      Another mechanism may involve excessive Ca2+ levels within the mitochondria which
      would cause this organelle's membrane to collapse ultimately inducing apoptosis
      and/or necrosis. With this in mind, it has been reported that in FSHD there is
      over expression of adenine nucleotide translocator-1 (ANT-1). This Ca2+ dependent
      protein, which is a component of the mitochondrial permeability transition pore,
      could be an important culprit in mitochondrial membrane collapse. Therefore,
      dysregulated Ca2+ as well as TNF-alpha, in addition to over-expression of ANT-1,
      may result in cell disruption ultimately causing the characteristic dystrophic
      muscle wasting. The present investigators have noted that some individuals with
      FSHD benefit from a regimen of diltiazem, a Ca2+ channel blocker. Initial results
      using diltiazem may represent the first beneficial treatment for a form of
      muscular dystrophy. Even if there is only a slowing of progression, this would be
      a positive first step. A combination of several different Ca2+ regulating agents
      and TNF-alpha inhibitors may be necessary to truly alter and/or reverse the
      deleterious effects of this form of muscular dystrophy.

PMID- 15963658
TI  - Cadmium, lead and phytochemicals.
AB  - Some metals are essential, others are found as contaminants in foodstuffs. There
      is some doubt on the antioxidant nature of foods or beverages containing
      phytochemicals because of cadmium and lead in foods. Evidence from
      epidemiological and experimental data has found an association between high fruit
      and vegetable intake and low cancer risk. However, these foods may also contain
      high amounts of carcinogenic metals, e.g., cadmium and lead shown to interfere
      with the repair of DNA damage. In this context, healthy and harmful effects of
      some nutrients are debated. As the benefits of a diet rich in fruits and
      vegetables are emphasized, attempts for regular mass administration of single
      food should be done prudently.

PMID- 15963659
TI  - Th2-biased immune response in cervical lymph nodes: animal models of Graves'
      disease might administer autoantigen to body regions where lymphatics drain to
      cervical lymph nodes.
AB  - It is believed that cervical lymph nodes have an important impact on Th2-biased
      immune response to central nervous system (CNS)-derived antigens. Obstruction of
      these nodes prior to a CNS-infusion of antigen markedly lowers the level of serum
      antibody response to the antigen. Graves' disease is a Th2-biased autoimmunity in
      which autoantibodies against thyrotropin receptor stimulate thyroid hormone
      production. The reasons for the distinct Th2-biased immune response in this
      hyperthyroidism are not fully understood, whereas most of the other human organ
      specific autoimmune diseases are believed to be Th1 mediated. It is suggested
      that the drainage of the thyroid lymphatics to cervical lymph nodes may play a
      role in the Th2-polarized immune response of Graves' disease. Thus, the
      generation of Graves' disease models by immunization may become more feasible if
      animals are administered the autoantigen to body regions whose lymph is drained
      to cervical lymph nodes.

PMID- 15963660
TI  - Radiation pneumonitis and pulmonary fibrosis in non-small-cell lung cancer:
      pulmonary function, prediction, and prevention.
AB  - Although radiotherapy improves locoregional control and survival in patients with
      non-small-cell lung cancer, radiation pneumonitis is a common treatment-related
      toxicity. Many pulmonary function tests are not significantly altered by
      pulmonary toxicity of irradiation, but reductions in D(L(CO)), the diffusing
      capacity of carbon monoxide, are more commonly associated with pneumonitis.
      Several patient-specific factors (e.g. age, smoking history, tumor location,
      performance score, gender) and treatment-specific factors (e.g. chemotherapy
      regimen and dose) have been proposed as potential predictors of the risk of
      radiation pneumonitis, but these have not been consistently demonstrated across
      different studies. The risk of radiation pneumonitis also seems to increase as
      the cumulative dose of radiation to normal lung tissue increases, as measured by
      dose-volume histograms. However, controversy persists about which dosimetric
      parameter optimally predicts the risk of radiation pneumonitis, and whether the
      volume of lung or the dose of radiation is more important. Radiation oncologists
      ought to consider these dosimetric factors when designing radiation treatment
      plans for all patients who receive thoracic radiotherapy. Newer radiotherapy
      techniques and technologies may reduce the exposure of normal lung to
      irradiation. Several medications have also been evaluated for their ability to
      reduce radiation pneumonitis in animals and humans, including corticosteroids,
      amifostine, ACE inhibitors or angiotensin II type 1 receptor blockers,
      pentoxifylline, melatonin, carvedilol, and manganese superoxide dismutase
      plasmid/liposome. Additional research is warranted to determine the efficacy of
      these medications and identify nonpharmacologic strategies to predict and prevent
      radiation pneumonitis.

PMID- 15963661
TI  - Grazing and vigilance by Soay sheep on Lundy island: influence of group size,
      terrain and the distribution of vegetation.
AB  - Animals allocate the time spent on different behaviours according to nutritional
      requirements, the distribution of food and the risk of predation. When the
      perceived predation risk is high, animals primarily behave in ways to increase
      their safety such as regularly scanning their surroundings, forming large groups
      and feeding in habitats with cover or high visibility. This study investigated
      which factors Soay sheep (Ovis aries) are most sensitive to in allocating time to
      different behaviours when the risk of predation is negligible. Continuous focal
      sampling was used to record the behaviour of the free-ranging Soay sheep on Lundy
      Island and measures of vegetation, group size and terrain were also recorded.
      Stepwise multiple regression produced a model of grazing with terrain and range
      of grass coverage as predictors and a model of vigilance with terrain as a
      predictor. Sheep grazed for longer on the slopes and as the range of grass cover
      decreased. They were more vigilant on the slopes. The results support the view
      that the group size effect largely depends on anti-predatory vigilance and
      suggest that time-budgets are more sensitive to other factors in the absence of
      predation.

PMID- 15963662
TI  - In vivo monitoring of PHA granule formation using GFP-labeled PHA synthases.
AB  - For the first time a functional protein was fused to a PHA synthase resulting in
      PHA granule formation and display of the respective function at the PHA granule
      surface. The GFP reporter protein was N-terminally fused to the class I PHA
      synthase of Cupriavidus necator (PhaC) and the class II PHA synthase of
      Pseudomonas aeruginosa PAO1 (PhaC1), respectively, while maintaining PHA synthase
      activity and PHA granule formation. Fluorescence microscopy studies of GFP-PHA
      synthase attached to emerging PHA granules indicated that emerging PHA granules
      locate to cell poles and to midcell representing the future cell poles. A rapid
      oscillating movement of GFP-PHA synthase foci from pole to pole was observed. In
      cell division impaired Escherichia coli, PHA granules were localized between
      nucleoids at regular spacing suggesting that nucleoid occlusion occurred.
      Accordingly, anucleate regions of the E. coli mukB mutant showed no regular
      spacing, but PHA granules with twofold increased diameter were formed. First
      evidence was provided that the cell division and the localization of GFP-PHA
      synthase foci are in vivo co-located.

PMID- 15963663
TI  - Minisatellite polymorphism as a tool to distinguish closely related Lactococcus
      lactis strains.
AB  - Genome plasticity is considered as a means for bacteria to adapt to their
      environment. Plasticity in tandem repeat sequences on bacterial genomes has been
      recently exploited to trace the epidemiology of pathogens. Here, we examine the
      utility of minisatellite (i.e., a repeat unit of six nucleotides or more) typing
      in non-pathogenic food bacteria of the species Lactococcus lactis. Thirty-four
      minisatellites identified on the sequenced L. lactis ssp. lactis strain IL1403
      genome were first analyzed in 10 closely related ssp. lactis strains, as
      determined by randomly amplified polymorphic DNA (RAPD). The selected tandem
      repeats varied in length, percent identity between repeats, and locations. We
      showed that: (i) the greatest polymorphism was in orfs encoding exported proteins
      or in intergenic regions; (ii) two thirds of minisatellites were little- or non
      variable, despite as much as 90% identity between tandem repeats; and (iii)
      dendrograms based on either RAPD or minisatellite analyses were similar. Seven
      minisatellites identified in this study are potentially useful for lactococcal
      typing. We then asked whether tandem repeats in L. lactis were stable upon very
      long-term (up to two years) storage. Despite large rearrangements previously
      reported in derivative strains, just one of 10 minisatellites tested underwent an
      alteration, suggesting that tandem repeat rearrangements probably occur during
      active DNA replication. We conclude that multiple locus minisatellite analysis
      can be a valuable tool to follow lactococcal strain diversity.

PMID- 15963664
TI  - Detection of a chloramphenicol efflux system in Escherichia coli isolated from
      poultry carcass.
AB  - An active chloramphenicol efflux system was demonstrated in a multiresistant E.
      coli isolated from poultry carcass. The effect of different concentrations of
      chloramphenicol on the original strain and on the plasmid-cured strain was
      determined in the presence and in the absence of CCCP, an uncoupler of the proton
      motive force. Minimal inhibitory concentration (MIC) was lower in the presence of
      CCCP in the original strain. The plasmid-cured strain displayed lower resistance
      for chloramphenicol than the wild type, but the MIC was not affected by CCCP. The
      combined results indicate a plasmid encoded energy dependent resistance
      mechanism. 3H-chloramphenicol accumulation within the cells was measured by
      scintillation counting. The uptake or the efflux of 3H-chloramphenicol was
      influenced by CCCP in the original strain, but not in the plasmid-cured strain.
      More than one chloramphenicol resistance mechanism may exist in this strain. E.
      coli is an important commensal or pathogen that inhabits the gastrointestinal
      tracts of humans and animals, so a plasmid encoded active drug resistance
      mechanism can be a potential source of horizontal transfer of resistance.

PMID- 15963665
TI  - The diversity of Mycoplasma hyopneumoniae within and between herds using pulsed
      field gel electrophoresis.
AB  - Over the years, pulsed-field gel electrophoresis (PFGE) has been proven a robust
      technique to type isolates with a high resolution and a good reproducibility. In
      this study, a PFGE protocol is described for the typing of Mycoplasma
      hyopneumoniae isolates. The potential of this technique was demonstrated by
      comparing M. hyopneumoniae isolates obtained from the same as well as from
      different herds. The use of two different restriction enzymes, SalI and ApaI, was
      evaluated. For each enzyme, the resulting restriction profiles were clustered
      using the unweighted pair group method with arithmetic means (UPGMA). For both
      obtained dendrograms, the included isolates of the related M. flocculare species
      clustered separately from all M. hyopneumoniae isolates, forming the root of the
      dendrograms. The PFGE patterns of the M. hyopneumoniae isolates of different
      herds were highly diverse and clustered differently in both dendrograms,
      illustrated by a Pearson's correlation coefficient of only 0.33. A much higher
      similarity was observed with isolates originating from different pigs of a same
      herd. The PFGE patterns of these isolates always clustered according to their
      herd and this for both dendrograms. In conclusion, the results indicate a closer
      relationship of M. hyopneumoniae isolates within a herd compared to isolates from
      different herds and this for both restriction enzymes used. Since the described
      PFGE technique was shown to be highly discriminative and reproducible, it will be
      a helpful tool to further elucidate the epidemiology of M. hyopneumoniae.

PMID- 15963666
TI  - New evidence regarding hormone replacement therapies is urgently required
      transdermal postmenopausal hormone therapy differs from oral hormone therapy in
      risks and benefits.
AB  - Controversies about the safety of different postmenopausal hormone therapies
      (HTs) started 30 years ago and reached a peak in 2003 after the publication of
      the results from the Women Health Initiative (WHI) trial and the Million Women
      Study (MWS) [Writing group for the women's health initiative investigations.
      Risks and benefits of estrogen plus progestin in healthy postmenopausal women.
      JAMA 2002;288:321-33; Million women study collaborators. Breast cancer and
      hormone-replacement therapy in the million women study. Lancet 2003;362:419-27].
      The single HT formulation used in the WHI trial for non hysterectomized women-an
      association of oral conjugated equine estrogens (CEE-0.625 mg/day) and a
      synthetic progestin, medroxyprogesterone acetate (MPA-2.5 mg/day)-increases the
      risks of venous thromboembolism, cardiovascular disease, stroke and breast
      cancer. The MWS, an observational study, showed an increased breast cancer risk
      in users of estrogens combined with either medroxyprogesterone acetate (MPA),
      norethisterone, or norgestrel. It is unclear and questionable to what extent
      these results might be extrapolated to other HRT regimens, that differ in their
      doses, compositions and administration routes, and that were not assessed in the
      WHI trial and the MWS. Significant results were achieved with the publication of
      the WHI estrogen-only arm study [Anderson GL, Limacher M, Assaf AR, et al.
      Effects of conjugated equine estrogen in postmenopausal women with hysterectomy:
      the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701
      1712] in which hormone therapy was reserved to women who had carried out
      hysterectomy. What emerged from this study will allow us to have some important
      argument to develop.

PMID- 15963667
TI  - The Jerusalem Balsam: from the Franciscan Monastery in the old city of Jerusalem
      to Martindale 33.
AB  - The Jerusalem Balsam, a remedy based on an ethanolic extract of a herbal mixture,
      was formulated in 1719 in the pharmacy of the Saint Savior monastery in the old
      city of Jerusalem. Having gained fame, the Jerusalem Balsam was replicated and
      prepared in Europe. One can still find variations of the formula in current
      pharmacopoeias (B.P., 1998. The Stationary Office, London, p. 1510; Sweetman,
      S.C., Blake, P.S., McGlashan, J.M., Parsons, A.V., 2002. Martindale: The Extra
      Pharmacopeia, 33rd ed. Pharmaceutical Press, London, p. 1101). We report here,
      five different formulas, all referred to as "The Jerusalem Balsam". Three of
      those formulas were translated and two of these translations are presented in the
      text. A third one is available as Supplementary data online. As the formulas
      originate from different historical periods, the Jerusalem Balsam may be a good
      case study of the development of pharmaceutical formulations over a 250 years
      period. One of the formulas, found in a manuscript form in the archive of the
      monastery, contains four plants: olibanum (Boswellia spp.), myrrh (Commiphora
      spp.), aloe (Aloe sp.) and mastic (Pistacia lentiscus L.). We conducted
      pharmacological assays on this four-plant formula. It showed anti-inflammatory,
      as well as anti-oxidative, and anti-septic properties.

PMID- 15963668
TI  - Polymorphous low-grade adenocarcinoma of the palate: report of cases.
AB  - OBJECTIVE: Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor that
      mostly affects minor salivary glands. The purpose of this study is to report six
      new cases followed-up during a long period. We also review the literature
      concerning clinical, histological and immunohistochemical features, as well as
      the proper management. METHODS: Malignant tumors of the salivary glands diagnosed
      in our department from 1990 to 1999 were reviewed. A total of 66 cases were
      registered. Six of these cases were diagnosed as PLGA. All cases satisfied the
      histopathological criteria for this entity, and at least 3 years follow-up was
      available. RESULTS: In the six cases the primary location was the mucosa of the
      palate. Hard palate was affected in 83.3% of the cases. There were no cases of
      extraoral PLGA in our series. Tumors were ulcerated in a 16.6% of the cases, and
      exofitic in the other 86.4%. Histologically, it was observed a tumoral
      proliferation of round clusters of uniform cells with round-to-oval clear nuclei
      and small nucleoli. All the cases underwent surgical management with local
      excision with surgical margins, five of them with bone extirpation associated. No
      recurrence was observed in four cases, whereas the remaining two cases showed
      recurrence in the follow-up. In one of the patients, lococervical recurrence
      appeared 12 months after the surgery, and this patient died after a few months.
      The remaining patients have been followed-up for 11, 7, 4 and 3 years
      postoperatively, with no evidence of recurrence. CONCLUSION: Our results for a
      long follow-up period support the idea for a low grade of malignancy and good
      prognosis of this tumor, but the appearance of recurrences many years after the
      surgery must induce us to be very careful and systematic with the follow-up.

PMID- 15963669
TI  - Stress fracture of the peroneal bone secondary to a complex tic.
AB  - Complex tics have been widely reported in literature, especially in children with
      Tourette syndrome. We describe the case of a fracture line of both peroneal bones
      in a 13-year-old child with Tourette syndrome and obsessive-compulsive disorder.
      He was admitted to our hospital because of pain in his legs. Radiography showed
      fractures of both peroneal bones, more marked on the left side. The clinical
      history was strongly suggestive of obsessive-compulsive disorder and Tourette
      syndrome with associated simple and complex motor tics. Radiographic follow-up
      showed spontaneous resolution of the fractures.

PMID- 15963670
TI  - Evolution of seizures and electroencephalographical findings in 23 cases of
      deletion type Angelman syndrome.
AB  - Angelman syndrome (AS) is a genetic disorder with characteristic clinical and EEG
      findings. We report here the results of long-term follow-up studies on the
      epileptic seizures and EEG findings of 23 cases of deletion type AS confirmed by
      FISH analysis, including seven cases previously reported by Matsumoto et al. in
      1992. The age at last follow-up in 23 patients was from 1 to 37 years of age
      (average: 18.0 years), with 10 patients (43.5%) in their 20s, and five over 30.
      Epileptic seizures were seen in all patients, and the age at seizure onset ranged
      from 3 to 50 months (average: 21.7 months). Status epilepticus was seen in 11
      patients (47.8%). The percentages of cases seizure-free for more than 3 years
      were 25% (4/16) at 10 years of age, 70% (7/10) at 20, and 80% (4/5) at 30. The
      EEG findings were classified into six patterns according to the previous report:
      N (no spike, including focal slow waves), HVS (diffuse high-voltage slow bursts
      with or without spikes), F (focal spikes or multifocal spikes), S (diffuse spike
      and waves), C (continuous diffuse spike and waves), Hy (hypsarrythmia or
      hypsarrhythmia like waves). Hy was noted at ages 0-2 years in two cases. C was
      observed from the ages 2 to 15 years, being most frequently noted at 3-6 years of
      age, and it was never seen after 16 years of age. S was observed from ages 1 to
      21 years. F was seen from 2 to 21 years of age, and most frequently during the
      ages of 2-7 years. HVS was seen from 0 years, and still remained after the age of
      20. After 22 years of age, all patients showed N pattern including focal slow
      waves. One of the two patients who had bilateral frontal dominant delta slow
      waves in their 30s, had a recent seizure. Even if the spikes disappear with age,
      when bi-frontal focal slow waves remain, seizures may occur even in patients over
      30.

PMID- 15963671
TI  - Management of drooling for children with neurological problems in Hong Kong.
AB  - OBJECTIVES: To share our experience in the management of drooling in Hong Kong,
      to describe the clinical profile of children with this problem, and to report the
      clinical outcome of oro-motor training. METHODS: Children attending the Drooling
      Clinic of Alice Ho Miu Ling Nethersole Hospital, Hong Kong between January 2000
      and June 2003 were included. Multidisciplinary assessment was performed to
      ascertain the medical condition, functional status and oro-motor difficulties of
      each child. Intervention might include optimization of medical condition, oro
      motor training and surgery. Severity of drooling was rated by a 10-point visual
      analogue scale (VAS). The outcome of oro-motor training was assessed by the
      change in VAS from baseline. RESULTS: Eight children, with a mean age of 11.9
      years, were included. Six children suffered from cerebral palsy and two had
      syndromal diagnoses. All had moderate or severe mental retardation. Poor lip
      closure, inadequate jaw control and delay in swallowing were common oro-motor
      difficulties. All children received oro-motor training. The mean duration of
      follow-up for seven children was 17 months. The mean baseline VAS was 7.1. When
      compared with the baseline, VAS rating during the training period decreased with
      a mean difference of 3.0. The difference remained at 1.9 at 4 months after
      training had stopped. Other functional gains, such as improved sucking and
      swallowing, were identified. Six caregivers declined surgery. One child improved
      and did not require surgery. CONCLUSIONS: Short-term follow-up of oro-motor
      training suggested beneficial outcome.

PMID- 15963672
TI  - Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the
      senescent rat soleus muscle.
AB  - Aging-related alterations of the ubiquitin proteasome pathway (UPP) have been
      reported in locomotor skeletal muscle. Specifically, declines in proteasome
      activity have been observed in the soleus of senescent animals compared to the
      soleus of young controls. However, the influence of aging on the mRNA levels of
      key components within the ubiquitin conjugation cascade (UCC) remains unknown. We
      hypothesized that aged soleus muscle would exhibit downregulated expression of
      select UCC mRNA and decreased levels of ubiquitin-protein conjugates. To test
      this postulate, we harvested soleus muscles from 6 and 24-26 month old Fisher 344
      rats. Aging resulted in a decline in mRNA expression of two key UCC components in
      soleus muscle; ubiquitin conjugating enzyme E2(14k) (E2(14k)) and muscle ring
      finger-1 (MuRF1). Surprisingly, no age-related differences existed in the total
      content of endogenous ubiquitin-protein conjugates in the soleus muscle.
      Nonetheless, a selective decrease in the level of ubiquitin-protein conjugates (
      approximately 30kDa) was detected in the soleus of senescent animals. These
      results indicate that the soleus muscle displays a differential mRNA response of
      select UCC components to aging. Furthermore, the decline in E2(14k) and MuRF1
      mRNA levels may contribute to altered substrate degradation by the UCC in the
      soleus muscle of senescent rats.

PMID- 15963673
TI  - Mitochondria, telomeres and cell senescence.
AB  - The accumulation of oxidative damage is one of the most widely accepted causes of
      ageing. Mitochondrial dysfunction, in particular damage to the mitochondrial DNA
      has been hypothesised, more than thirty years ago, as responsible for increased
      production of reactive oxygen species (ROS) and, thus, as one possible causal
      factor for ageing. There is now a wealth of data that supports this hypothesis,
      which is mostly derived from models considering the ageing of post-mitotic or
      slowly dividing cells in vivo. One major cellular model of ageing, however, is
      replicative senescence, the irreversible loss of division potential of somatic
      cells after a more or less constant number of cell divisions. Not much data
      exists concerning the role of mitochondria in this model. Here, we review
      evidence supporting an involvement of mitochondria in replicative senescence and
      a possible link to telomere shortening.

PMID- 15963674
TI  - Neurofibromatosis type 1: diffusion weighted imaging findings of brain.
AB  - PURPOSE: The purposes of this study were to evaluate the differences in apparent
      diffusion coefficient (ADC) values between infra and supratentorial unidentified
      bright objects (UBOs), between UBOs and normal appearing side (NAS, contralateral
      regions of the UBOs and/or normal appearing region without UBOs) in the
      neurofibromatosis type 1 patients (NF1) and control group and also to investigate
      correlation between age and ADC values. METHODS: A total of 30 patients and 26
      healthy controls were included. The MRI examination consisted of routine imaging
      and diffusion weighted imaging (DWI). Seven distinct locations (frontal, parieto
      occipital and cerebellar white matter, globus pallidum, thalamus, hippocampus,
      and midbrain) were selected for the analysis. The ADC values were calculated
      directly from these automatically generated ADC maps with ROI. RESULTS: The ADC
      values of UBOs were significantly increased in cerebellar white matter,
      hippocampus, globus pallidum, midbrain, and thalamus when compared with NAS and
      control group. There were statistically significant differences between NAS and
      control group in the ADC values obtained from hippocampus and thalamus. There
      were statistically significant differences between supra and infratentorial UBOs
      in ADC values. There was a negative correlation between age and the ADC values
      obtained from normal appearing midbrain, hippocampus, thalamus, and globus
      pallidum. CONCLUSION: ADC values both in UBOs and in the normal appearing
      locations as hippocampus and thalamus were detected to be higher in the patients
      with NF1. The detection of lesions might be independent of MRI appearance in NF1,
      i.e. although the brain is affected, MRI appearance may be normal. Therefore, DWI
      and ADC values should also be utilized in the delineation of brain involvement of
      NF1 patients.

PMID- 15963675
TI  - Analysis of macrolide antibiotics by liquid chromatography.
AB  - A compilation of the most representative single and multianalyte HPLC methods for
      the analysis of macrolide antibiotics published during the last two decades is
      presented in this paper. Its scope is the coverage of two main areas which
      require the determination of macrolide antibiotics at a low concentration level,
      i.e. pharmacokinetic studies and residue analysis. Both of these areas involve
      the treatment of biological and foodstuff matrices, respectively. A detailed
      explanation of the different sample preparation procedures as well as the
      experimental conditions and the main analytical features are provided for each
      referred method in order to allow the reader to select the most suitable
      conditions for their particular purpose.

PMID- 15963676
TI  - Development of a rapid and sensitive LC-ESI/MS/MS assay for the quantification of
      propofol using a simple off-line dansyl chloride derivatization reaction to
      enhance signal intensity.
AB  - A rapid, selective and sensitive method was developed for the determination of
      propofol concentration using an off-line dansyl chloride derivatization step to
      enhance signal intensity. The method consisted of a protein precipitation
      extraction followed by derivatization with dansyl chloride and analysis by liquid
      chromatography ionspray tandem mass spectrometry (LC-ESI/MS/MS). The separation
      was achieved using a 100 mm x 2 mm C8 analytical column combined with an
      isocratic mobile phase composed of 80:20 acetonitrile: 0.5% formic acid in water.
      Signal intensity of the propofol-dansyl chloride derivative was increased up to
      200-fold as compared to the underivatized propofol in positive electrospray mode.
      An analytical range of 20-20,000 ng/mL was used in the calibration curve of
      plasma and blood samples. The novel method met all requirements of specificity,
      sensitivity, linearity, precision, accuracy and stability. A pharmacokinetic
      study was performed in rats and the novel analytical method was used as a routine
      analysis to provide enhanced measurements of plasma and blood concentrations of
      propofol. Blood and plasma pharmacokinetic results show that a very important
      fraction of propofol distributes into red blood cells. In conclusion, a rapid and
      sensitive LC-ESI/MS/MS method using a derivatization agent was developed to
      enhance signal intensity of propofol. Routine analysis with the novel method
      provided accurate results and enhanced the detection levels of plasma and blood
      concentrations of propofol to better characterize the in vivo biodisposition of
      propofol.

PMID- 15963677
TI  - Validation of immunoassays used to assess immunogenicity to therapeutic
      monoclonal antibodies.
AB  - Immunogenicity has always been an important consideration in the evaluation of
      pharmaceutical protein biologics. In this article, method validation parameters
      relevant to enzyme immunoassays are described for assays applied to the analysis
      of anti-drug antibodies, with special considerations for immunogenicity to
      therapeutic monoclonal antibodies. Common strategies for experimental
      investigation of various validation parameters are proposed. In addition, a
      novel, yet simple, approach is proposed to categorize the validation effort into
      two mutually interdependent phases, based on the characterization of validation
      parameters as "system descriptive" or "system controlled". System descriptive
      parameters are those that must be characterized but need not have pre-specified
      acceptance criteria for assay validation. In contrast, system-controlled
      parameters should be understood early in assay development, and optimized and
      confirmed using a priori acceptance criteria in validation to assure sufficient
      control over them during routine bioanalysis. This approach not only streamlines
      the validation process but also eliminates unnecessary redundancies. This
      validation method can be achieved with proper scientific rigor and remain within
      the realm of GLP compliance. The authors hope that other research groups would
      engage in discussions on validation of anti-drug antibody assays in order to
      establish a consistent approach across the industry and academia.

PMID- 15963678
TI  - Metabolic barrel representations with various patterns of neonatal whisker
      deafferentation in rats.
AB  - With various patterns of whisker deafferentation, C3 whisker stimulation produced
      divergently shaped metabolic barrel representations in layer IV of the primary
      somatosensory cortex. Whisker deafferentation results in functional and
      structural reorganization of the barrels in the primary somatosensory cortex. The
      present study examines the alteration of the metabolic barrel representations in
      layer IV with various configurations of selective whisker deafferentation in
      neonates, using [14C]2-deoxyglucose autoradiography. The deafferentation was
      produced by unilateral ablation of whiskers, leaving certain follicles intact.
      Configurations of intact follicles included: (I) row C follicles; (II) B3, C3,
      and D3 follicles; (III) B3, B4, C3, and C4 follicles; (IV) C2, C3, D2, and D3
      follicles. The metabolic C3 barrel representations in layer IV after the
      deafferentations were found to have expanded only toward the barrel sites in
      which the corresponding whiskers were ablated, with no expansion toward the
      neighboring barrels. Expansion toward row D was significantly more pronounced
      than expansion toward row B, and expansion toward the C2 barrel was significantly
      more pronounced than expansion toward the C4 barrel. From these results, it can
      be inferred that asymmetric intrinsic structural connections are reflected in the
      functional metabolic barrel representation under the condition of neural
      plasticity in the barrel cortex following whisker deafferentation.

PMID- 15963679
TI  - [Management of subjects in a state of brain death and the preservation of
      organs].

PMID- 15963680
TI  - A high-throughput colorimetric and fluorometric microassay for the evaluation of
      nitroimidazole derivatives anti-trichomonas activity.
AB  - Several nitroimidazole derivatives were synthesized and tested as possible
      trichomonicidal agents. A fast, simple, practical and reliable in vitro
      colorimetric method was applied to the screening of the nitroimidazole
      derivatives anti-trichomonas activity. The colorimetric technique was based on
      the use of Alamar blue as a redox-indicator. The test was carried out both
      qualitatively (minimal inhibitory concentration determined by naked eye
      observation) and quantitatively (fluorometric determination of 50% and 90%
      inhibitory concentrations), the latter took advantage of the dye fluorometric
      properties. The performance of the method was excellent affording an exactitude
      97.86% and a reproducibility of 95% and no interference of the trichomonas
      culture medium was observed during the test. Some of the nitroimidazole compounds
      tested showed a fair trichomonicidal activity, however none of them was as active
      as the model compound, metronidazole.

PMID- 15963681
TI  - Lack of the effect of mycotoxins-aflatoxin B1 and ochratoxin A on some functions
      of rat adipocytes.
AB  - Mycotoxins-aflatoxin B1 (AFB1) and ochratoxin A (OTA)-compounds which are strong
      carcinogenic, mutagenic and cytotoxic factors-are also known to evoke a decrease
      of food intake and body weight gains. The purpose of our study was to determine
      the direct influence of AFB1 and OTA incubated with isolated rat fat cells on the
      lipogenesis, lipolysis and leptin secretion. Adipocytes were isolated from the
      epididymal fat tissue by the collagenase digestion. Toxins used at concentrations
      1, 10 and 100 microM were incubated for 90 min with adipocytes. Basal and insulin
      stimulated lipogenesis-determined by the measure of [U-14C]glucose conversion to
      total lipids-was abated by AFB1 only at the highest concentration. At two lower
      ones, AFB1 did not affect the process. OTA at all used concentrations decreased
      insulin-stimulated lipogenesis but the effect was not dose-dependent. The
      lipolysis was determined by the measure of glycerol release from adipocytes. The
      basal lipolysis was unchanged by both toxins. The epinephrine-stimulated
      lipolysis was intensified by AFB1 only at the highest concentration, however, the
      process was not altered by OTA. The antilipolytic action of insulin was
      unaffected by both compounds (10 microM). To determine the influence of the
      tested toxins on leptin secretion, adipocytes were incubated for 120 min in the
      presence of glucose and insulin as stimulators of hormone secretion. AFB1 and OTA
      added to the incubation medium (1, 10 and 100 microM) had no significant
      influence on the leptin release. The results obtained in this experiment
      demonstrate that adipocytes are susceptible to the direct action of AFB1 and OTA.
      This susceptibility is, however, rather weak and is exhibited by a slight
      restriction of the lipogenesis (in the case of both toxins) and by a slight
      increase of the lipolysis (in the case of AFB1).

PMID- 15963682
TI  - Inhibitory effect of Buthus martensi Karsch extracts on interleukin-1beta-induced
      expression of nitric oxide (NO) synthase and production of NO in human
      chondrocytes and LPS-induced NO and prostaglandin E2 production in mouse
      peritoneal macrophages.
AB  - We examined the effect of Buthus martensi Karsch (BMK) extract on IL-1beta
      induced production of nitrogen oxide (NO) in primary human osteoarthritis (OA)
      chondrocytes. The cells were treated with BMK (10 microg/ml) and IL-1beta (2
      ng/ml) for different periods, and inducible nitric oxide synthase (iNOS) mRNA and
      protein expression were determined by real-time quantitative reverse
      transcriptase-polymerase chain reaction and Western blotting, respectively. The
      cytotoxicity of BMK on human OA chondrocytes was very low (IC50 > 250 microg/ml)
      as measured by the XTT assay method. Production of NO was determined as nitrite
      in culture supernatant. Human chondrocytes cotreated with BMK produced
      significantly less NO compared with chondrocytes stimulated with IL-1beta alone.
      Activation and translocation of and NF-(kappa)B DNA binding activity were
      determined by Western blotting and specific enzyme-linked immunosorbent assay.
      The inhibition of NO production correlated with the suppression of induction and
      expression of nuclear factor-kappaB (NF-(kappa)B) and activation protein-1 (AP-1)
      dependent gene. BMK inhibited the activation and translocation of NF-(kappa)B to
      the nucleus, indicating that BMK inhibits the IL-1beta-induced production of NO
      in human chondrocytes by interfering with the activation of NF-(kappa)B through a
      novel mechanism. In addition, BMK reduced prostaglandin E2 (PGE2) production in
      mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no
      influence on the activity of inducible NO synthase (iNOS), cyclooxygenase-2 (COX
      2) or cyclooxygenase-1 (COX-1) was observed. Our data, therefore, suggest that
      BMK may be a therapeutically effective inhibitor of IL-1beta-induced inflammatory
      effects that are dependent on NF-(kappa)B activation in human OA chondrocytes.
      The results indicate that BMK exerts anti-inflammatory effects related to the
      inhibition of neutrophil functions and of NO and PGE2 production, which could be
      due to a decreased expression of iNOS and COX-2 through the transcription factors
      NF-(kappa)B and AP-1.

PMID- 15963683
TI  - Serial analysis of gene expression in the silkworm, Bombyx mori.
AB  - The silkworm Bombyx mori is one of the most economically important insects and
      serves as a model for Lepidoptera insects. We used serial analysis of gene
      expression (SAGE) to derive profiles of expressed genes during the developmental
      life cycle of the silkworm and to create a reference for understanding silkworm
      metamorphosis. We generated four SAGE libraries, one from each of the four
      developmental stages of the silkworm. In total we obtained 257,964 SAGE tags, of
      which 39,485 were unique tags. Sorted by copy number, 14.1% of the unique tags
      were detected at a median to high level (five or more copies), 24.2% at lower
      levels (two to four copies), and 61.7% as single copies. Using a basic local
      alignment search tool on the EST database, 35% of the tags matched known silkworm
      expressed sequence tags. SAGE demonstrated that a number of the genes were up- or
      down-regulated during the four developmental phases of the egg, larva, pupa, and
      adult. Furthermore, we found that the generation of longer cDNA fragments from
      SAGE tags constituted the most efficient method of gene identification, which
      facilitated the analysis of a large number of unknown genes.

PMID- 15963684
TI  - Low-dose endotoxemia and human neuropsychological functions.
AB  - Epidemiological data demonstrate an association between systemic low-grade
      inflammation defined as 2- to 3-fold increases in circulating inflammatory
      mediators and age-related decline in cognitive function. However, it is not known
      whether small elevations of circulating cytokine levels cause direct effects on
      human neuropsychological functions. We investigated changes in emotional,
      cognitive, and inflammatory parameters in an experimental in vivo model of low
      grade inflammation. In a double-blind crossover study, 12 healthy young males
      completed neuropsychological tests before as well as 1.5, 6, and 24 h after an
      intravenous injection of Escherichia coli endotoxin (0.2 ng/kg) or saline in two
      experimental sessions. Endotoxin administration had no effect on body
      temperature, cortisol levels, blood pressure or heart rate, but circulating
      levels of tumor necrosis factor (TNF) and interleukin (IL)-6 increased 2- and 7
      fold, respectively, reaching peak values at 3 h, whereas soluble TNF-receptors
      and IL-1 receptor antagonist peaked at 4.5 h. The neutrophil count increased and
      the lymphocyte count declined. In this model, low-dose endotoxemia did not affect
      cognitive performance significantly but declarative memory performance was
      inversely correlated with cytokine increases. In conclusion, our findings
      demonstrate a negative association between circulating IL-6 and memory functions
      during very low-dose endotoxemia independently of physical stress symptoms, and
      the hypothalamo-pituitary-adrenal axis.

PMID- 15963685
TI  - Influence of exercise training and age on CD14+ cell-surface expression of toll
      like receptor 2 and 4.
AB  - The influence of an exercise training program and age on inflammatory cytokine
      production and CD14+cell-surface expression of toll-like receptor 2 (TLR2) and
      toll-like receptor 4 (TLR4) was examined in 60 younger and older subjects.
      Subjects were assigned to: young physically active (YPA, n = 15; 25.2 +/- 5.0
      years), young physically inactive (YPI, n = 14; 24.9 +/- 4.7 years), older
      physically active (OPA, n = 14; 71.2 +/- 4.4 years) or older physically inactive
      (OPI, n = 17; 71.0 +/- 4.3 years) groups. YPI and OPI completed 12 weeks (3
      days/week) of endurance (20 min) and resistance exercise (eight exercises, two
      sets). YPA and OPA groups were instructed to continue their normal activity for
      12 weeks. Blood was collected at rest, before and after the 12-week training and
      control period. A whole blood method was used to determine lipopolysaccharide
      (LPS) and peptidoglycan-(PGN) stimulated IL-6, IL-1beta, and TNF-alpha production
      with supernatants analyzed using ELISA. CD14+ cell-surface expression of TLR2 and
      TLR4 were measured using flow cytometry. Training increased estimated VO(2max) by
      10.4% and increased strength by an average of 38.1%. YPI and OPI had a post
      training reduction in LPS-stimulated IL-6 production (P < .01), but LPS
      stimulated IL-1beta and TNF-alpha and PGN-stimulated cytokines were not changed.
      CD14+ cell TLR4 was significantly reduced (P < .05) in YPI and OPI groups after
      training, but TLR2 was not significantly changed. An exercise training program
      reduced LPS-stimulated IL-6, concomitant with lower TLR4. These results provide
      further support for a training- or physical activity-induced lowering of TLR4 and
      inflammation.

PMID- 15963686
TI  - Evaluating and increasing in-home leisure activity among adults with severe
      disabilities in supported independent living.
AB  - Observations were conducted of the in-home leisure activity of three adults with
      severe disabilities in three supported independent living (SIL) sites. Results
      indicated a lack of leisure engagement. Potentially preferred, typical leisure
      activities were then identified by consulting lists of common leisure activities,
      surveying adults in surrounding communities, and interviewing support staff and
      family members. Next, in-home staffs were trained to provide the identified
      leisure activities in a repeated, paired-choice manner. Results indicated
      increased leisure engagement for each participant when staff provided leisure
      choices along with brief prompting. Social validation surveys suggested the
      choice procedures were well received by the staff and participants. Comparison
      observations of nine adults in other SIL arrangements in two states indicated the
      low levels of engagement initially observed in the three target homes may be
      quite common among people with severe disabilities in SIL. Results are discussed
      regarding use of behavioral procedures to evaluate and improve aspects of quality
      of life in SIL. Future research needs noted focus on how to impact staff
      performance and consumer lifestyles in residential settings in which supervision
      is infrequent.

PMID- 15963687
TI  - The effectiveness of group therapy for students with mild voice disorders: a
      controlled clinical trial.
AB  - Previous studies of students studying to be teachers have indicated that these
      students commonly have voice disorders. Ideally, voice disorders should be
      treated before students start their work as teachers, but the resources for this
      treatment are often limited. This study examines whether group voice therapy is
      effective for teacher students. Accordingly, 20 teacher students with mild voice
      disorders received group voice therapy (in three small groups), whereas 20
      students with similar voice disorders served as a control group and consequently
      did not receive voice therapy. Two out of three outcome measures (perceptual
      evaluation of voice quality and a questionnaire on the occurrence of vocal
      symptoms) indicated significant changes in the treatment group compared with the
      control group. No differences between groups were noted in the laryngeal status.
      The results suggest that group voice therapy seems to be an effective method to
      treat students with mild voice disorders.

PMID- 15963688
TI  - Vocal process avulsion.
AB  - Vocal process avulsion is a rare complication of intubation or external laryngeal
      trauma that can cause significant dysphonia. The vocal process develops
      independently from the body of the arytenoid cartilage, which results in a fusion
      plane that is vulnerable to trauma. The findings of vocal process avulsion may be
      subtle, and the relationship of the vocal process to the body of the arytenoid
      cartilage must be examined closely. Stroboscopy is critical in the evaluation. We
      describe three cases of vocal process avulsion encountered by the senior author
      (R.T.S.) over the last 5 years and discuss our approaches to evaluation and
      treatment. All cases were repaired endoscopically. However, we used three
      different techniques. These include chemical tenotomy with botulinum toxin,
      closed reduction with fat injection, and open reduction via cordotomy.

PMID- 15963689
TI  - Emotion understanding from the perspective of autonomous robots research.
AB  - In this paper, I discuss some of the contributions that modeling emotions in
      autonomous robots can make towards understanding human emotions-'as sited in the
      brain' and as used in our interactions with the environment-and emotions in
      general. Such contributions are linked, on the one hand, to the potential use of
      such robotic models as tools and 'virtual laboratories' to test and explore
      systematically theories and models of human emotions, and on the other hand to a
      modeling approach that fosters conceptual clarification and operationalization of
      the relevant aspects of theoretical notions and models. As illustrated by an
      overview of recent advances in the field, this area is still in its infancy.
      However, the work carried out already shows that we share many conceptual
      problems and interests with other disciplines in the affective sciences and that
      sound progress necessitates multidisciplinary efforts.

PMID- 15963690
TI  - Biological engineering applications of feedforward neural networks designed and
      parameterized by genetic algorithms.
AB  - Two neural network (NN) applications in the field of biological engineering are
      developed, designed and parameterized by an evolutionary method based on the
      evolutionary process of genetic algorithms. The developed systems are a fault
      detection NN model and a predictive modeling NN system. An indirect or 'weak
      specification' representation was used for the encoding of NN topologies and
      training parameters into genes of the genetic algorithm (GA). Some a priori
      knowledge of the demands in network topology for specific application cases is
      required by this approach, so that the infinite search space of the problem is
      limited to some reasonable degree. Both one-hidden-layer and two-hidden-layer
      network architectures were explored by the GA. Except for the network
      architecture, each gene of the GA also encoded the type of activation functions
      in both hidden and output nodes of the NN and the type of minimization algorithm
      that was used by the backpropagation algorithm for the training of the NN. Both
      models achieved satisfactory performance, while the GA system proved to be a
      powerful tool that can successfully replace the problematic trial-and-error
      approach that is usually used for these tasks.

PMID- 15963691
TI  - Emotion recognition through facial expression analysis based on a neurofuzzy
      network.
AB  - Extracting and validating emotional cues through analysis of users' facial
      expressions is of high importance for improving the level of interaction in man
      machine communication systems. Extraction of appropriate facial features and
      consequent recognition of the user's emotional state that can be robust to facial
      expression variations among different users is the topic of this paper. Facial
      animation parameters (FAPs) defined according to the ISO MPEG-4 standard are
      extracted by a robust facial analysis system, accompanied by appropriate
      confidence measures of the estimation accuracy. A novel neurofuzzy system is then
      created, based on rules that have been defined through analysis of FAP variations
      both at the discrete emotional space, as well as in the 2D continuous activation
      evaluation one. The neurofuzzy system allows for further learning and adaptation
      to specific users' facial expression characteristics, measured though FAP
      estimation in real life application of the system, using analysis by clustering
      of the obtained FAP values. Experimental studies with emotionally expressive
      datasets, generated in the EC IST ERMIS project indicate the good performance and
      potential of the developed technologies.

PMID- 15963692
TI  - Omega incision face-lift approach and SMAS rotation advancement flap in
      parotidectomy for prevention of contour deficiency and conspicuous scars
      affecting the neck.
AB  - To overcome the disadvantages after the surgical removal of tumours of the
      parotid gland, especially the depressed facial deformity and conspicuous cervical
      scar formation subsequent to parotid surgery, we have concentrated on omega face
      lift incision in combination with an SMAS rotation advancement flap for the last
      several years using a lazy omega incision. Nine patients (3 male and 6 female)
      ranging in age from 43 to 68 years (mean age: 56.3 years) fulfilled the selection
      criterion of having a clinically benign discrete parotid lump with a benign
      preoperative fine needle cytology result. Parotidectomy was performed using the
      modified omega face-lift incision in conjunction with the rotation advancement
      SMAS flap. All patients underwent follow-up every 3 months in the first year.
      During the follow-up, the patients were specifically asked about their
      satisfaction with the post-operative appearance and whether they would consent to
      the operation again. The vascularized SMAS rotation advancement flap is
      clinically simple to perform and provides satisfactory cosmetic and functional
      results in patients undergoing conservative parotidectomy. There are no drawbacks
      in the use of modified face-lift incision to remove tumours of the parotid gland.

PMID- 15963693
TI  - Regional striatal volume abnormalities in schizophrenia: effects of comorbidity
      for alcoholism, recency of alcoholic drinking, and antipsychotic medication type.
AB  - Striatal structures form critical nodes of multiple circuits that are implicated
      in the pathophysiology of schizophrenia and alcoholism. Here, we examined the
      separate and combined effects of schizophrenia and alcoholism and effects of
      medication type and drinking recency on striatal volumes. Accordingly, we
      measured caudate nucleus, putamen, and nucleus accumbens in 27 schizophrenic, 25
      alcohol-dependent, 19 comorbid (schizophrenia and alcohol dependence or abuse),
      and 51 age-matched control men. Schizophrenics were classified by antipsychotic
      medication (typical or atypical), and alcoholics were classified by recency of
      sobriety. All measured structures were smaller in the patient groups than the
      control group. The caudate deficit was comparable across groups, whereas putamen
      and nucleus accumbens deficits were greater in schizophrenia than alcoholism;
      comorbids fell between these groups. Schizophrenic patients treated with atypical
      medication showed greater volume deficits in the putamen than those treated with
      typical medication. Recently sober (<3 weeks) alcoholics had greater deficits in
      nucleus accumbens than longer sober drinkers. In conclusion, caudate, putamen,
      and nucleus accumbens exhibited different patterns of volume deficit in patients
      with alcoholism and schizophrenia alone, with no evidence for compounded deficits
      in comorbid patients. Further, these cross-sectional data provide indirect
      support for at least partial recovery of nucleus accumbens volume with sobriety
      in alcoholics, regardless of schizophrenia comorbidity.

PMID- 15963694
TI  - Synergistic effect of antibacterial agents human beta-defensins, cathelicidin LL
      37 and lysozyme against Staphylococcus aureus and Escherichia coli.
AB  - BACKGROUND: The antimicrobial properties of the skin are attributed to several
      agents including human beta-defensins (hBDs), cathelicidin LL-37 and skin
      lysozyme. Although these antibacterial agents reside in the skin to protect it
      against infection, it is not well known whether the total analysis of all
      combinations of these agents may result in synergistic effect to enhance their
      antibacterial activities against invading microorganisms. OBJECTIVE: To elucidate
      the interactions between keratinocyte-derived antibacterial agents in the
      extracellular milieu, we investigated the individual and synergistic activities
      of hBDs, LL-37 and lysozyme against Staphylococcus aureus and Escherichia coli in
      neutral and acidic milieus. METHODS: The colorimetric method using alamarBlue was
      employed to assess the antibacterial activities of hBD-1, -2, -3, LL-37 and
      lysozyme and the viability of bacteria was read spectrophotometrically. RESULTS:
      In both neutral and acidic pH milieus, hBD-1, -2, -3, LL-37 and lysozyme
      exhibited antibacterial activity against S. aureus and E. coli in a dose
      dependent manner. Interestingly, the antibacterial activity of hBD-1, -2, -3 and
      lysozyme but not LL-37 was significantly enhanced in acidic milieu (pH 4.6).
      Furthermore, various combinations of above agents resulted in a synergistic or
      additive antibacterial effect against S. aureus and E. coli in neutral milieu.
      The synergistic effect of hBDs, LL-37 and lysozyme against S. aureus was further
      significantly enhanced in acidic milieu. In contrast, above antibacterial agents
      exhibited mainly additive rather than synergistic effect on antibacterial
      activity against E. coli in acidic milieu. CONCLUSION: Taken together, these
      results provide a novel evidence of antimicrobial mechanism of natural human skin
      derived antibacterial agents against bacterial infection, and their involvement
      in innate immunity.

PMID- 15963695
TI  - Treating respiratory tract infections in ambulatory care in Belgium:
      fluoroquinolone consumption and resistance development.
AB  - This study analyses consumption patterns of fluoroquinolones in treating
      respiratory tract infections in ambulatory care in Belgium and describes
      susceptibility of Streptococcus pneumoniae isolates to fluoroquinolones.
      Consumption data were obtained from IMS Health. Pneumococcal resistance was
      investigated in 600 blood isolates collected from 1998 to 2003. Although
      consumption of fluoroquinolones has increased rapidly over the last decade, this
      trend does not seem to persist more recently. Fluoroquinolones were mainly used
      to treat urinary and lower respiratory tract infections, but rarely in the
      management of upper respiratory tract infections. The use of new fluoroquinolones
      (levofloxacin, moxifloxacin) and the ongoing use of older fluoroquinolones have
      not led to increased pneumococcal resistance, which remained below 1% for
      levofloxacin and was 0% for moxifloxacin.

PMID- 15963696
TI  - Effects of molecular mass and hydrophobicity on transport rates through non
      specific pathways of the silkworm larva midgut.
AB  - We previously reported that therapeutic drug effects in the silkworm infection
      model are largely influenced by midgut permeability. In this report, we describe
      the effects of drug molecular mass and hydrophobicity on transport through the
      silkworm larva midgut membrane. Hydrophilic compounds with a molecular mass of
      greater than 400Da did not permeate the silkworm larva midgut, and the
      hydrophobicity of similar-sized compounds had positive effects on the transport
      rate. Furthermore, we compared transport rates through the midgut membrane
      between cefcapene sodium (CFPN-Na) and cefcapene pivoxil (CFPN-PI), which is a
      CFPN-Na prodrug. The in vitro transport rate of CFPN-PI was three times faster
      than that of CFPN-Na. Moreover, when CFPN-PI and CFPN-Na were injected into the
      living silkworm larva midgut, CFPN-PI appeared rapidly in the haemolymph, whereas
      CFPN-Na did not. The 50% effective dose (ED50) of CFPN-PI administered via the
      midgut was one-sixth that of CFPN-Na. These findings suggest that the general
      features of the non-specific transport route are similar between silkworm larvae
      and mammals.

PMID- 15963698
TI  - Research on mental disorders and their care in immigrant populations: a review of
      publications from Germany, Italy and the UK.
AB  - OBJECTIVE: The review aims to identify the extent and nature of research on
      mental disorders and their care in immigrant populations in three major European
      countries with high levels of immigration, i.e. Germany, Italy, United Kingdom
      (UK). METHOD: Peer-reviewed publications on the subject from the three countries
      between 1996 and 2004 were analyzed. The research questions addressed, the
      methods used, and the results obtained were assessed. RESULTS: Thirteen papers
      reporting empirical studies were found from Germany, four from Italy and 95 from
      the UK. Studies addressed a range of research questions and most frequently
      assessed rates of service utilization in different immigrant groups. The most
      consistent finding is a higher rate of hospital admissions for Afro-Caribbean
      patients in the UK. Many studies had serious methodological shortcomings with low
      sample sizes and unspecified inclusion criteria. DISCUSSION: Despite large scale
      immigration in each of the three studied countries, the numbers of relevant
      research publications vary greatly with a relatively high level of empirical
      research in the UK. Possible reasons for this are a generally stronger culture of
      mental health service research and a higher number of researchers who are
      themselves from immigrant backgrounds in the UK. CONCLUSION: Overall the evidence
      base to guide the development of mental health services for immigrant populations
      appears limited. Future research requires appropriate funding, should be of
      sufficient methodological quality and may benefit from collaboration across
      Europe.

PMID- 15963697
TI  - Erythromycin resistance in the commensal throat flora of patients visiting the
      general practitioner: a reservoir for resistance genes for potential pathogenic
      bacteria.
AB  - The prevalence and mechanism of erythromycin resistance in commensal throat
      streptococci was determined from October 2000 until December 2002 as part of an
      ongoing study of the NIVEL in general practice patients (N=678). Resistance
      prevalence for 1mg/L and 16 mg/L erythromycin was 57% and 20%, respectively. The
      percentage of total commensal flora resistant within each patient ranged from 1%
      to 100% (median, 1%). mefA was predominantly found among isolates on the 1mg/L
      plates, and ermB was found in 64% of the isolates on the 16 mg/L plates.
      Erythromycin resistance was transferred from a commensal isolate to Streptococcus
      pneumoniae with a frequency of 1 x 10(-9). Commensal streptococci of general
      practice patients in The Netherlands form a large reservoir of transferable
      erythromycin resistance (genes) for potential pathogenic microorganisms.

PMID- 15963699
TI  - Hallucinogen persisting perception disorder after psilocybin consumption: a case
      study.
AB  - The recurrence of flashbacks without acute or chronic hallucinogen consumption
      has been recognized in the DSM IV criteria as the hallucinogen persisting
      perception disorder (HPPD). Perceptual disturbances may last for 5 years or more
      and represent a real psychosocial distress. We reported here a case of a 18-year
      old young man presenting HPPD after a mixed intoxication with psylocibin and
      cannabis. This report shows symptomatic recurrences persisting more than 8
      months. Various differential diagnoses were evoked and our therapeutic strategies
      were described.

PMID- 15963700
TI  - Prevalence and incidence of Parkinson's disease in Europe.
AB  - OBJECTIVE: To provide an overview on the prevalence and incidence of Parkinson's
      disease (PD) in selected European countries. BACKGROUND: PD is a common disease
      of unknown etiology. Accurate information on the epidemiology of PD is critical
      to inform health policy. An aging population will lead to more patients with PD;
      thus, the high financial burden PD places on society will increase. MATERIAL AND
      METHODS: A systematic literature search was performed to identify studies on the
      prevalence and incidence of PD in the following European countries: Austria, the
      Czech Republic, France, Germany, Italy, The Netherlands, Portugal, Spain, Sweden
      and United Kingdom. Only published studies were included. Abstracts, reviews,
      meta-analyses and letters to the editor were excluded. There were no language
      restrictions. Data were extracted using a standardized assessment form, and
      evidence tables were used to systematically report and compare the data. RESULTS:
      Of 39 identified studies, most (87%) reported estimates of PD prevalence rates,
      while only a few (13%) reported estimates of PD annual incidence rates. Crude
      prevalence rate estimates ranged from 65.6 per 100,000 to 12,500 per 100,000 and
      annual incidence estimates ranged from 5 per 100,000 to 346 per 100,000. No
      publications could be identified for Austria or the Czech Republic. DISCUSSION
      AND CONCLUSION: The observed variations in prevalence and incidence rates may
      result from environmental or genetic factors, but might also be a consequence of
      differences in methodologies for case ascertainment, diagnostic criteria, or age
      distributions of the study populations. The comparability of existing studies is
      limited.

PMID- 15963701
TI  - Analysis of pathological defects in methionine metabolism using a simple
      mathematical model.
AB  - Derangements in methionine metabolism are a hallmark of cancers and
      homocystinuria, an inborn error of metabolism. In this study, the metabolic
      consequences of the pathological changes associated with the key pathway enzymes,
      methionine adenosyl transferase (MAT), glycine N-methyl transferase (GNMT) and
      cystathionine beta-synthase (CBS) as well as an activation of polyamine
      metabolism, were analyzed using a simple mathematical model describing methionine
      metabolism in liver. The model predicts that the mere loss of allosteric
      regulation of CBS by adenosylmethionine (AdoMet) leads to an increase in
      homocysteine concentration. This is consistent with the experimental data on the
      corresponding genetic defects, which specifically impair allosteric activation
      but not basal enzyme activity. Application of the characteristics of transformed
      hepatocytes to our model, i.e., substitution of the MAT I/III isozyme by MAT II,
      loss of GNMT activity and activation of polyamine biosynthesis, leads to the
      prediction of a significantly different dependence of methionine metabolism on
      methionine concentrations. The theoretical predictions were found to be in good
      agreement with experimental data obtained with the human hepatoma cell line,
      HepG2.

PMID- 15963702
TI  - Experimental hand pain delays recognition of the contralateral hand--evidence
      that acute and chronic pain have opposite effects on information processing?
AB  - Recognising the laterality of a pictured hand involves making an initial decision
      and confirming that choice by mentally moving one's own hand to match the
      picture. This depends on an intact body schema. Because patients with complex
      regional pain syndrome type 1 (CRPS1) take longer to recognise a hand's
      laterality when it corresponds to their affected hand, it has been proposed that
      nociceptive input disrupts the body schema. However, chronic pain is associated
      with physiological and psychosocial complexities that may also explain the
      results. In three studies, we investigated whether the effect is simply due to
      nociceptive input. Study one evaluated the temporal and perceptual
      characteristics of acute hand pain elicited by intramuscular injection of
      hypertonic saline into the thenar eminence. In studies two and three, subjects
      performed a hand laterality recognition task before, during, and after acute
      experimental hand pain, and experimental elbow pain, respectively. During hand
      pain and during elbow pain, when the laterality of the pictured hand corresponded
      to the painful side, there was no effect on response time (RT). That suggests
      that nociceptive input alone is not sufficient to disrupt the working body
      schema. Conversely to patients with CRPS1, when the laterality of the pictured
      hand corresponded to the non-painful hand, RT increased approximately 380 ms (95%
      confidence interval 190 ms-590 ms). The results highlight the differences between
      acute and chronic pain and may reflect a bias in information processing in acute
      pain toward the affected part.

PMID- 15963703
TI  - Stress stimulation induced resistance of plant.
AB  - During the course of pathogens penetrating the plant cell, besides of chemical
      secretion, the pathogens may cause mechanical signal by the physical pressure on
      the plant cell. In the current study, we took the stress as the mechanical signal
      elicitor to find the effect of plant resistance induced by stress. The results
      showed that an appropriate stress stimulation can evidently improve the plant
      resistance. However, disruption the plasma membrane-cell wall adhesion will
      absolutely eliminate this kind of inducement effect, which suggests that the
      plant resistance inducement by stress depend on the adhesion of plasma membrane
      cell wall. Also we found that stress stimulation may cause synthesis of lignin
      and increase the activity of phenylalaninc ammonial lyase (PAL) chitinase and
      beta-1,3-glucanase obviously. The results showed that stress stimulation may not
      only enhance ability of the plant cell resistant to pathogen penetration but also
      elicit the accumulation of pathogens suppression or antimicrobial chemical
      substance in the plant cell.

PMID- 15963704
TI  - The Shigella flexneri serotype Y vaccine candidate SFL124 originated from a
      serotype 2a background.
AB  - Shigella flexneri is endemic in most developing countries and responsible for the
      highest mortality rate among the Shigella species. The attenuated serotype Y S.
      flexneri strain SFL124 has been used as the parental strain for the development
      of recombinant vaccines expressing multiple O-antigen structures. During the
      development of one such multivalent vaccine, a region of gtrII homology was found
      in SFL124. Sequencing and analysis of this region revealed the presence of an
      insertion element interrupted serotype 2a serotype-conversion locus in the
      serotype Y vaccine strain SFL124. The data presented suggests that SFL124 has
      derived from a serotype 2a background.

PMID- 15963705
TI  - Identification of antimicrobial compounds active against intracellular
      Staphylococcus aureus.
AB  - Small-colony variants (SCVs) of Staphylococcus aureus exhibit characteristics of
      bacteria that can penetrate mammalian cells and remain intracellular and
      innocuous for indefinite periods. These properties make SCVs a convenient tool
      that can be used to identify new antibacterial agents having activity against
      intracellular, quiescent bacteria. Agents active against SCVs could be useful in
      the treatment of chronic staphylococcal infections such as bovine mastitis. An
      hemB deletion mutant of S. aureus Newbould, a bovine mastitis isolate, having a
      stable, genetically defined SCV phenotype, was used in a screening program to
      identify compounds active against intracellular, gram-positive bacteria. Out of
      more than 260,000 compounds screened, nine compounds having the desired
      properties were identified. The range of MICs against gram-positive bacteria was
      < or = 0.12-32 microg ml-1. One of the compounds (no. 8) showed excellent
      activity against gram-positive (MICs < or = 0.12 microg ml-1) and gram-negative
      (MICs < or = 0.12-4 microg ml-1) bacteria. Each of the nine compounds
      demonstrated efficacy in a neutropenic mouse thigh infection model. Two
      compounds, including compound no. 8, reduced numbers of bacteria in a mouse
      mastitis model of infection. Application of a stepwise screening process has
      identified lead compounds that may be useful for treating persistent,
      intracellular infections.

PMID- 15963706
TI  - Oral probiotic bacterial administration suppressed allergic responses in an
      ovalbumin-induced allergy mouse model.
AB  - This study investigated whether orally administered probiotic bacteria
      (Bifidobacterium bifidum and Lactobacillus casei) and a gram-negative bacterium
      (Escherichia coli) function as allergic immune modulators to prevent food
      allergy, according to the hygiene hypothesis. C3H/HeJ mice were sensitized with
      ovalbumin (OVA) and cholera toxin for 5 weeks. After sensitization, the OVA
      induced mice that were not treated with bacteria had significantly increased
      levels of OVA-specific IgE, total IgE, and IgG1 in sera, as well as scab-covered
      tails. In comparison, groups treated with B. bifidum BGN4 (BGN4), L. casei 911
      (L. casei), or Escherichia coli MC4100 (E. coli) had decreased levels of OVA
      specific IgE, total IgE, and IgG1, and decreased levels of mast cell
      degranulation and tail scabs. OVA-specific IgA levels were decreased in BGN4- and
      L. casei-treated groups. In conclusion, administration of E. coli, BGN4, or L.
      casei decreased the OVA-induced allergy response. However, a normal increase in
      body weight was inhibited in the E. coli-treated mice and in the montreated mice
      groups during allergy sensitization. Thus, BGN4 and L. casei appear to be useful
      probiotic bacteria for the prevention of allergy.

PMID- 15963707
TI  - Prostaglandin E2 production in ovarian cancer cell lines is regulated by
      cyclooxygenase-1, not cyclooxygenase-2.
AB  - The significance of cyclooxygenase-2 (COX-2) expression in ovarian cancer has
      been discussed. In this study, we found increased expression of COX-1 mRNA and
      protein in three out of 10 ovarian cancer cell lines. Prostaglandin E 2 (PGE2)
      production was elevated in these three cell lines, but not in other seven cell
      lines. COX-2 protein was not detected in any of the cell lines. Cytosolic
      prostaglandin E synthase (cPGES) mRNA and protein were detected in all 10 cell
      lines. Membrane-associated PGES-1 (mPGES-1) was detected in some of the ovarian
      cell lines, but its presence did not correspond with PGE2 production. In
      contrast, mPGES-2 mRNA and protein were detected in all 10 cell lines. A
      nonselective COX inhibitor (indometacin) and a selective COX-1 inhibitor (SC-560)
      strongly inhibited PGE2 production by the three cell lines, while selective COX-2
      inhibitors (NS-398 and rofecoxib) did not inhibit PGE2 production. In addition,
      increased expression of COX-1, not COX-2 protein was observed in the mass of
      ovarian cancer tissues from 22 patients when compared with that in normal tissue.
      These findings suggest that COX-1 might be a major enzyme regulating PGE2
      production in ovarian cancer cells.

PMID- 15963708
TI  - Virulence factors, pathogenesis and vaccine protection in cholera and ETEC
      diarrhea.
AB  - Recent work has provided new insights into the pathogenesis of the potentially
      life-threatening diarrheas caused by Vibrio cholerae and enterotoxigenic
      Escherichia coli (ETEC): a new mechanism (post-translational degradation), which
      is involved in the control of cholera toxin expression, has been discovered.
      Recent evidence also suggests that vibrios upregulate cholera toxin expression in
      response to intestinal fluid components, and enterotoxin-carrying bacterial outer
      membrane vesicles might have a function in ETEC pathogenesis. An important role
      of the environment is supported by the correlation between cholera incidence and
      elevated sea surface temperature, which supports the notion that the zooplankton
      is a V. cholerae reservoir. Additionally, environmental lytic cholera phages
      could influence cholera seasonality by 'terminating' the seasonal epidemic.
      Finally, the strong herd immunity elicited by an oral cholera vaccine indicates
      that cholera vaccination could have a significant public health impact.

PMID- 15963709
TI  - Host innate and Th1 responses and the bacterial factors that control
      Mycobacterium tuberculosis infection.
AB  - It is clear that resistance against acute tuberculosis (TB) is dependent on the
      host's ability to generate Th1 immunity. Nevertheless, the role of host immunity
      in latent TB remains incompletely defined. Recent progress in elucidating host
      innate and adaptive immune responses to M. tuberculosis (Mtb) and their impact on
      latent infection includes identification of TLR2-dependent anti-inflammatory
      responses, a MyD88-independent, non-protective Th1 response, the formation of
      secondary lymphoid follicles in granulomas and the role of Th1 responses, IFN
      gamma and TNF-alpha in preventing re-activation of infection; IFN-gamma also
      appears to be involved in activating latency genes in Mtb. When Mtb re-infects a
      patient, it appears to localize in established granulomas; however, different
      bacterial strains may behave differently. Although these advances do not provide
      all the answers regarding host defense mechanisms, they nevertheless bring us
      closer to new and better design strategies for immunotherapy and
      immunoprophylaxis.

PMID- 15963710
TI  - Working with NKT cells--pitfalls and practicalities.
AB  - Our understanding of NKT cells has been rapidly advancing over recent years, with
      many research groups studying how these cells behave and how they can be
      manipulated to prevent disease. Although good progress has been made, a
      difficulty is the lack of a clear consensus about how to assay, or even identify,
      NKT cells. The different approaches have been an ongoing source of uncertainty
      about the biological behaviour and function of NKT cells and have complicated
      efforts to define their role in immunity. An important step towards reaching
      agreement on the behaviour of NKT cells is to have a clear appreciation of the
      advantages and disadvantages of the different approaches that are employed in
      this field of study. This should help determine the most appropriate ways to
      investigate NKT cell function, thus bringing us closer to successfully exploiting
      these cells in the treatment of human diseases.

PMID- 15963711
TI  - A study of the natural biodegradation of two-phase olive mill solid waste during
      its storage in an evaporation pond.
AB  - A study of the natural biodegradation of two-phase olive mill solid waste (OMSW)
      during its storage in an evaporation pond was carried out. This system is
      traditionally used as the final disposal of this waste or constitutes a previous
      stage before being processed by cogeneration or anaerobic digestion processes. A
      laboratory-scale pond with a total volume of 520 l was used. The experiment was
      carried out between December 2002 and August 2003 covering a total period of 269
      days. During the experiment, the variations of temperature (outside and inside
      the pond), the effective volume of the OMSW in the pond, moisture content, total
      solids (TS), volatile solids (VS), the total chemical oxygen demand (TCOD), total
      volatile acids (TVA), pH and cumulative methane production as a function of the
      operation time were evaluated. The experimental results obtained showed that the
      characteristics of the two-phase OMSW in the pond were dependent on the time of
      operation and temperature. During the experiment, three periods were clearly
      observed and differentiated: (a) An initial period with a rapid reduction of
      moisture content and effective volume, with an increase of TS, VS and TCOD
      removals, a decrease of pH and an increase of TVA and methane production until
      day 21. (b) A second period of slow decrease of moisture content and effective
      volume, due to the decrease of the ambient temperature. This period took place
      between day 21 and days 120-150 of assay, and it was characterised by a slight
      change in the OMSW properties. (c) A third period where the characteristics of
      the waste in the pond changed considerably due to the increase of the temperature
      outside the pond. The methane gas production also showed an increase due to the
      increase of methanogenic activity with the increase of temperature. An empirical
      model to describe the changes of two-phase OMSW characteristics and methane
      production with the operation time was developed. The proposed model, based on
      the use of polynomial equations, took into account the influence of the
      temperature and fit adequately into the experimental results obtained. It was
      found that the pond could probably be used as preliminary treatment of two-phase
      OMSW before its anaerobic digestion process, because a maximum conversion of
      organic matter to TVA was obtained after an operation time of around 200 days.

PMID- 15963712
TI  - Adhesion proteins and the control of cell shape.
AB  - The adherens junction functions to connect epithelial cells and maintain their
      polarized architecture. The geometry of the adherens junction, and consequently
      the shape of a cell, appears to reach an energetically favorable state. Cadherins
      within the adherens junction are necessary for cells to achieve this state.
      However, the view of an adherens junction as a static structure is at odds with
      the highly dynamic properties of epithelia during development. Interactions
      between the actin cytoskeleton and the adherens junction are required for certain
      cell shape changes. Recent insights into adherens junction remodeling have
      revealed the importance of polarized localization of myosin and Par3 at the
      adherens junction.

PMID- 15963713
TI  - Population-based survival of children in New Zealand diagnosed with cancer during
      1990-1993.
AB  - In this study, we have aimed to characterise the survival of all 0-14 year-old
      New Zealand children who were diagnosed with cancer during 1990-1993. Four
      hundred and nine children were followed up using two largely independent sources.
      We calculated Kaplan-Meier survival probabilities and investigated various
      prognostic factors using the Cox model. Five-year survival for all cancers was
      66% (95% confidence interval (CI) 62-71%) and for acute lymphoblastic leukaemia
      it was 70% (CI 62-79%). Cancers with particularly favourable prognoses (followed
      by their respective 5-year survival probabilities) included: retinoblastoma 100%
      (CI 74-100%), Hodgkin's disease 93% (CI 79-100%), non-Hodgkin's lymphoma 87% (CI
      73-100%) and osteosarcoma 91% (CI 74-100%). Cancers with poor prognoses included:
      neuroblastoma 35% (CI 14-56%), rhabdomyosarcoma 42% (CI 14-70%) and central
      nervous system tumours 49% (CI 38-60%). Girls with any cancer had a significantly
      lower risk of death than boys. Generally, survival for childhood cancers in New
      Zealand increased greatly between 1961-1965 and 1990-1993. Nevertheless, outcomes
      for some cancers remained poor.

PMID- 15963714
TI  - Strain improvement for tannase production from co-culture of Aspergillus foetidus
      and Rhizopus oryzae.
AB  - Spores from the co-culture of Aspergillus foetidus and Rhizopus oryzae were
      subjected to UV, heat and NTG (3-nitro,5-methylguanidine) mutagenesis. A few
      colonies were screened from the selected media for tannase study. Amongst all,
      the best mutant isolated from the heat treatment (60 degrees C for 60 min) was
      SCPR 337. The maximum yield of gallic acid and tannase in case of mutant strain
      was 95.2% and 53.6 U/ml with an incubation period of 30 h as compared to wild
      strain where the incubation period was 48 h with an enzyme activity of 44.2 U/ml
      and gallic acid yield of 94%, respectively. The mutant was sensitive to
      tetracycline and was also an over-producer of protease and amylase.

PMID- 15963715
TI  - Effects of feedstock, airflow rate, and recirculation ratio on performance of
      composting systems with air recirculation.
AB  - The thermodynamics, kinetics, and energy use of composting systems with air
      recirculation were determined for feedstocks comprising paper mill sludge and
      biosolids. Results were developed by simulating the composting system using a two
      dimensional finite difference numerical model. Incorporated into the simulation
      model was independent regulation of temperature and oxygen using a closed loop
      feedback control system with a two-stage fan setting. Results showed that at low
      airflows and high recirculation ratios, heat removal by the exhaust gas was
      insufficient to maintain set point temperatures with the result that process
      temperatures increased and eventually limited the reaction rate. Types of
      feedstock, magnitude of airflow and recirculation ratio all affected the energy
      use of the system. Although recirculation leads to high energy use, it can
      produce high quality compost by having a temperature gradient of less than 2
      degrees C across the bed.

PMID- 15963716
TI  - Oryza sativa L. husk as heavy metal adsorbent: optimization with lead as model
      solution.
AB  - The effects of initial concentration of lead, temperature, biomass loading and pH
      were investigated for an optimized condition of lead uptake from the aqueous
      solution. The optimization process was analyzed using Central Composite Face
      Centered Experimental Design in Response Surface Methodology (RSM) by Design
      Expert Version 5.0.7 (StatEase, USA). The design was employed to derive a
      statistical model for the effect of parameters studied on the removal of lead ion
      from aqueous solution. The coefficient of determination, R2 was found to be
      92.36%. The initial concentration of 50.0 mg/L, temperature of 60 degrees C,
      biomass loading of 0.2 g and pH of 5.0 had been found to be the optimum
      conditions for the maximum uptake of lead ions in 98.11% batch mode. Under the
      optimum conditions, the lead uptake was attained to be circa 8.60 mg/g.

PMID- 15963717
TI  - Lime enhanced chromium removal in advanced integrated wastewater pond system.
AB  - The removal of trivalent chromium from a combined tannery effluent in horizontal
      settling tanks and subsequent Advanced Integrated Wastewater Pond System (AIWPS)
      reactors was investigated. The raw combined effluent from Modjo tannery had pH in
      the range of 11.2-12. At this pH, a trivalent chromium removal of 46-72% was
      obtained in the horizontal settling tanks after a one-day detention time.
      Trivalent chromium precipitated as chromium hydroxide, Cr(OH)3. 58-95% Cr(III)
      was removed in the advanced facultative pond (AFP) where the water column pH of
      7.2-8.4 was close to pH 8, which is the optimum precipitation pH for trivalent
      chromium. Chromium removals in the secondary facultative pond (SFP) and
      maturation pond (MP) were 30-50% and 6-16%, respectively. With Cr(III)
      concentration of 0.2-0.8 mg/l in the final treated effluent, the AIWPS preceded
      by horizontal settling tanks produced effluent that could easily meet most of the
      current Cr(III) discharge limits to receive water bodies.

PMID- 15963718
TI  - High surface area activated carbon prepared from cassava peel by chemical
      activation.
AB  - Cassava is one of the most important commodities in Indonesia, an agricultural
      country. Cassava is one of the primary foods in our country and usually used for
      traditional food, cake, etc. Cassava peel is an agricultural waste from the food
      and starch processing industries. In this study, this solid waste was used as the
      precursor for activated carbon preparation. The preparation process consisted of
      potassium hydroxide impregnation at different impregnation ratio followed by
      carbonization at 450-750 degrees C for 1-3 h. The results revealed that
      activation time gives no significant effect on the pore structure of activated
      carbon produced, however, the pore characteristic of carbon changes significantly
      with impregnation ratio and carbonization temperature. The maximum surface area
      and pore volume were obtained at impregnation ratio 5:2 and carbonization
      temperature 750 degrees C.

PMID- 15963719
TI  - Impurity analysis of retinoic acid samples.
AB  - The structure of an impurity contained in samples of all trans-retinoic acid was
      established by means of NMR and MS spectra, and confirmed by X-ray diffraction
      analysis. The chemical structure of the impurity 2 was found to be strictly
      correlated to the synthetic procedure employed for the preparation of the
      retinoic acid samples. Single crystal analysis allowed us to characterise the
      molecular conformation and the crystal structure of 2.

PMID- 15963720
TI  - Gastric cytoprotective activity of ilicic aldehyde: structure-activity
      relationships.
AB  - A series of sesquiterpene compounds possessing both eudesmane and eremophilane
      skeletons were tested as gastric cytoprotective agents on male Wistar rats. The
      presence of an alpha,beta-unsaturated aldehyde on the C-7 side chain together
      with a hydroxyl group at C-4 is the requirement for the observed antiulcerogenic
      activity. In an attempt to establish new molecular structural requirements for
      this gastric cytoprotective activity, a structure-activity study was performed.

PMID- 15963721
TI  - Bioactive fluorinated derivative of amphotericin B.
AB  - The first stably fluorinated derivative of amphotericin B2 with a fluorine atom
      in the macrolide skeleton was synthesized using an electrophilic fluorination
      reagent, Selectfluor. The derivative 2 showed hemolytic, K+ permeable, and
      antifungal activities similar to those of AmB and thus was expected to be a
      powerful tool for NMR-based investigations on the mechanism of ion-channel
      formation by amphotericin B.

PMID- 15963722
TI  - Synthesis and biological activity of mustard derivatives of combretastatins.
AB  - A series of chimeric compounds bearing the combretastatin and the nitrogen
      mustard cores were synthesized. All the compounds were cytotoxic and inhibited
      tubulin polymerization. When combretastatin was joined to chlorambucil via an
      ester linkage, the resultant compound proved to be significantly more potent than
      the two compounds put together. When combretastatin was joined to nitrogen
      mustard via an ether linkage or when a true hybrid was synthesized, loss of
      potency was observed. Nonetheless, these latter compounds appeared to be more
      efficacious and surprisingly were able to inhibit tubulin depolymerization at
      high concentrations.

PMID- 15963723
TI  - 3-(1,2,3-Triazol-1-yl)-1-thio-galactosides as small, efficient, and
      hydrolytically stable inhibitors of galectin-3.
AB  - Copper(I)-catalyzed addition of alkynes to methyl 3-azido-3-deoxy-1-thio-beta-D
      galactopyranoside afforded stable and structurally simple 3-deoxy-3-(1H-1,2,3
      triazol-1-yl)-1-thio-galactosides carrying a panel of substituents at the
      triazole C4 in high yields. The 3-(1H-[1,2,3]-triazol-1-yl)-1-thio-galactoside
      collection synthesized contained inhibitors of the tumor- and inflammation
      related galectin-3 with Kd values as low as 107 microM, which is as potent as the
      natural disaccharide inhibitors lactose and N-acetyllactosamine.

PMID- 15963724
TI  - Can nurses interpret X-rays safely without formal tuition?
AB  - This work looks at the skill of X-ray interpretation that nurses working in
      Accident and Emergency have achieved without being provided any formal tuition on
      the topic. It shows that nurses do indeed learn whilst at work and that with a
      little forethought develop skills that can benefit patients and lead to service
      improvements.

PMID- 15963725
TI  - An enhanced protocol to reduce error in electromagnetic tracking of first
      metatarsophalangeal joint motions.
AB  - BACKGROUND: Error associated with markers or sensors surface-mounted onto skin
      reduces the validity of kinematic models. Extensor tendon excursion at the first
      metatarsophalangeal joint (MTPJ) has been noted previously to be especially
      problematic. An enhanced skin mounting protocol is described and validated.
      METHODS: A Fastrak system was used to obtain kinematic data concurrently from two
      pairs of sensors mounted on either side of the first MTPJ of nine freshly frozen
      cadaveric feet. One sensor pair was mounted directly into the medulla of each of
      the first metatarsal and proximal phalanx of the hallux, with the second pair
      attached to the skin over the same segments, using each of two mounting
      protocols. A standard mounting protocol was compared to a new enhanced protocol
      that secured the sensor on the hallux with a stabilizing cuff. RESULTS: The
      addition of a stabilizing cuff on the hallux sensor reduced root mean square
      error in first MTPJalpha rotations by 1.45 degrees during passive rotation and
      1.61 degrees during active rotation compared with the standard protocol (P =
      0.008 and 0.028, respectively). The cuff protocol improved CMC reliability
      coefficients for alpha rotations from 0.918 to 0.973 for passive MTPJ motion, and
      from 0.922 to 0.973 for active motion. CONCLUSION: Securing the hallux mounted
      sensor with a stabilizing cuff reduced error by more than one-third without
      reducing first MTPJ total range of motion.

PMID- 15963726
TI  - Exploration of a binding mode of indole amide analogues as potent histone
      deacetylase inhibitors and 3D-QSAR analyses.
AB  - Docking simulations and three-dimensional quantitative structure-activity
      relationship (3D-QSAR) analyses were conducted on a series of indole amide
      analogues as potent histone deacetylase inhibitors. The studies include
      comparative molecular field analysis (CoMFA) and comparative molecular similarity
      indices analysis (CoMSIA). Selected ligands were docked into the active site of
      human HDAC1. Based on the docking results, a novel binding mode of indole amide
      analogues in the human HDAC1 catalytic core is presented, and enzyme/inhibitor
      interactions are discussed. The indole amide group is located in the open pocket,
      and anchored to the protein through a pair of hydrogen bonds with Asp99 O-atom
      and amide NH group on ligand. Based on the binding mode, predictive 3D-QSAR
      models were established, which had conventional r2 and cross-validated
      coefficient values (r(cv)2) up to 0.982 and 0.601 for CoMFA and 0.954 and 0.598
      for CoMSIA, respectively. A comparison of the 3D-QSAR field contributions with
      the structural features of the binding site showed good correlation between the
      two analyses. The results of 3D-QSAR and docking studies validate each other and
      provided insight into the structural requirements for activity of this class of
      molecules as HDAC inhibitors. The CoMFA and CoMSIA PLS contour maps and MOLCAD
      generated active site electrostatic, lipophilicity, and hydrogen-bonding
      potential surface maps, as well as the docking studies, provided good insights
      into inhibitor-HDAC interactions at the molecular level. Based on these results,
      novel molecules with improved activity can be designed.

PMID- 15963727
TI  - Metabolism of anthocyanins and their phenolic degradation products by the
      intestinal microflora.
AB  - Anthocyanins are suggested to be responsible for protective effects against
      cardiovascular diseases and certain forms of cancer. Although previous studies
      have implicated that intact anthocyanidin glycosides were decreased extensively
      by interactions in the gastrointestinal tract, only few data are available
      concerning the metabolism by the intestinal microflora. Using a new in vitro
      model, we have investigated the microbial deglycosylation and degradation of six
      anthocyanins exhibiting three different aglycones with mono- or di-beta-D
      glycosidic bonds using high-performance liquid chromatography-diode array (HPLC
      DAD) and gas chromatography-mass spectrometry (GC-MS) detection. We have found
      that all anthocyanidin glycosides were hydrolysed by the microflora within 20 min
      and 2 h of incubation depending on the sugar moiety. Due to the high instability
      of the liberated aglycones at neutral pH, primary phenolic degradation products
      were already detected after 20 min of incubation. Further metabolism of the
      phenolic acids was accompanied by demethylation. Because of their higher chemical
      and microbial stability, phenolic acids and/or other, not yet identified,
      anthocyanin metabolites might be mainly responsible for the observed antioxidant
      activities and other physiological effects in vivo.

PMID- 15963728
TI  - Development of semi-automated system for preparation of (188)Re aqueous solutions
      of high and reproducible activity concentrations.
AB  - A semi-automated system has been developed for elution and concentration of the
      (188)Re-eluate from 111 GBq (3 Ci) (188)W/(188)Re-generators to provide a
      dissolved beta-source of high (188)Re-activity per unit volume. The elution
      progress and concentration were precisely and continuously monitored by use of
      collimated diode detectors. By using ion exchange cartridges, small eluate
      volumes (2-3 ml) of maximum 40 GBq, (188)Re/ml activity concentration were
      routinely prepared. The concentrated (188)Re solutions were used to beta
      irradiate aqueous suspensions and solutions of iodine species to evaluate a
      simulation of the extent of radiolytic decomposition of chemical species (AgI and
      CH(3)I) expected to accumulate in the containment sump of a nuclear reactor in
      the event of a severe accident with reproducible dose rates of up to 0.4 Gys(-1).
      Results have shown that AgI colloidal particles decompose to varying extents,
      depending on conditions, and in proportion to their initial mass, which indicates
      surface oxidation. Experiments have also confirmed CH(3)I decomposition in
      proportion to initial aqueous concentration.

PMID- 15963729
TI  - Right atrial aneurysm treated with atrioplasty without using cardiopulmonary
      bypass in an infant.
AB  - A 7-month-old female child was diagnosed to have a massive right atrial aneurysm,
      presented with arrhythmias. She was treated by restorative right atrioplasty
      without using cardiopulmonary bypass. She had good postoperative outcome and a 5
      month follow-up remains uneventful. In the absence of major congenital heart
      defects, aneurysm of right atrium can be treated without using cardiopulmonary
      bypass.

PMID- 15963730
TI  - The place of gastro-jejuno-duodenal interposition following limited esophageal
      resection.
AB  - OBJECTIVE: Although stomach is the best choice for reconstruction after
      esophagectomy from the viewpoint of safety and ease, an intrathoracic stomach,
      nevertheless, is a poor long-term substitute. This anatomical configuration
      abolishes normal antireflux mechanisms and places the acid-excreting stomach
      subject to biliary reflux, moreover, in an adjacent position to the esophagus
      within the negative-pressure environment of the thorax. METHODS: Between 1995 and
      2002, 27 patients with high-grade neoplasia-as early Barrett's carcinoma-or non
      dilatable peptic stricture underwent limited surgical resection of the distal
      esophagus and esophagogastric junction. In 11 of these cases, the reconstruction
      was performed with gastro-jejuno-duodenal interposition. The long-term functional
      results of this specially adapted form of interposition reconstruction have been
      evaluated. The postoperative follow-up period ranged between 24 and 95 months
      (mean 68 months). Nine patients (9/11=81.8%) have agreed to undergo endoscopy,
      radiographic contrast-swallow examination, and 24-h ambulatory esophageal pH and
      bilirubin monitoring. RESULTS: Three out of nine patients (3/9=33%) demonstrated
      abnormal levels of esophageal acid exposure during the 24-h study period, whilst
      none had any evidence of bilirubin exposure in the esophageal remnant. Endoscopy
      revealed that three patients had reflux esophagitis in the remnant esophagus: Los
      Angeles A=2, C=1. No stomal or jejunal ulceration at the gastro-jejunal
      anastomosis could be observed. Histopathologic assessment of the squamous
      epithelial biopsies demonstrated microscopic evidence of inflammation: minor in
      two cases, moderate in one and major in one case; however, none of them had
      evidence of columnar metaplasia in the esophageal remnant at a median of 68
      months after surgery. The majority of the patients have been doing well since the
      operation: 8/9 (88%)=Visick I-II. CONCLUSIONS: Gastro-jejuno-duodenal
      interposition represents an adequate 'second-best' method of choice if technical
      difficulties emerge with jejunal or colon interposition following limited
      resection of the esophagus performed due to early Barett's carcinoma or non
      dilatable peptic stricture.

PMID- 15963731
TI  - Bone marrow microenvironmental changes in aged mice compromise V(D)J recombinase
      activity and B cell generation.
AB  - B cell generation and immunoglobulin (Ig) diversity in mice is compromised with
      aging. Our recent work sought to understand mechanism(s) that contribute to
      reduced B cell production in aged mice. Using in vivo labeling, we found that
      reduction in marrow pre-B cells reflects increased attrition during passage from
      the pro-B to pre-B cell pool. Analyses of reciprocal bone marrow (BM) chimeras
      reveal that the production rates of pre-B cells are controlled primarily by
      microenvironmental factors, rather than intrinsic events. To understand changes
      in pro-B cells that could diminish production of pre-B cells, we evaluated rag2
      expression and V(D)J recombinase activity in pro-B cells at the single cell
      level. The percentage of pro-B cells that express rag2 is reduced in aged mice
      and is correlated with both a loss of V(D)J recombinase activity in pro-B cells
      and reduced numbers of pre-B cells. Reciprocal BM chimeras revealed that the aged
      microenvironment also determines rag2 expression and recombinase activity in pro
      B cells. These observations suggest that extrinsic factors in the BM that decline
      with age are largely responsible for less efficient V(D)J recombination in pro-B
      cells and diminished progression to the pre-B cell stage. These extrinsic factors
      may include cytokines and chemokines derived from BM stromal cells that are
      essential to the development of B cell precursors. The changes during aging
      within the BM hematopoietic microenvironment most likely are linked to the
      physiology of aging bone. Bone degrades with age (osteoporosis) due to decreased
      formation of new bone by osteoblasts. Marrow stem cells (MSC) are considered the
      progenitor of both adipocytes, osteoblasts and hematopoietic stromal cells and a
      controlled reciprocal regulation exists of osteoblast versus adipocyte
      differentiation; with age adipocytes increase, and osteoblast decrease. It is
      possible that stromal cell generation from MSC is compromised during aging.
      Currently, understanding of BM microenvironmental factors that regulate rag gene
      expression is very limited. However, as early progenitors differentiate, it is
      increasing clear that a limited set of transcription factors (e.g. ikaros, PU.1,
      E2A, EBF, pax5) regulate B-lineage specific genes, and that expression and
      stability of these factors is responsive to the microenvironment. Current and
      future work by several groups will strive to understand mechanisms that regulate
      these factors and how aging impacts these regulatory circuits.

PMID- 15963733
TI  - Studies of the structural change during deformation in Cryptomeria japonica by
      time-resolved synchrotron small-angle X-ray scattering.
AB  - A definite proportional limit which has been observed typically in metallic
      materials during the transition from elastic deformation into plastic one was
      also detected in the load-displacement curve of the compression wood with the
      water content about 100% from Cryptomeria japonica D. Don. Time-resolved small
      angle X-ray scattering studies demonstrated a large structural change, that is, a
      strong decrease in the microfibril angle in the cell wall occurring with
      increasing the displacement beyond the proportional limit for the compression
      wood loaded in uniaxial tension. Correspondingly, the mechanical properties are
      changed and high elongations begin to be seen. For the dried normal wood, on the
      other hand, only a weak decrease in the microfibril angle was observed with
      increasing the elongation until the fracture is initiated, where the elastic
      behavior was maintained.

PMID- 15963732
TI  - Modeling dynamic reciprocity: engineering three-dimensional culture models of
      breast architecture, function, and neoplastic transformation.
AB  - In order to understand why cancer develops as well as predict the outcome of
      pharmacological treatments, we need to model the structure and function of organs
      in culture so that our experimental manipulations occur under physiological
      contexts. This review traces the history of the development of a prototypic
      example, the three-dimensional (3D) model of the mammary gland acinus. We briefly
      describe the considerable information available on both normal mammary gland
      function and breast cancer generated by the current model and present future
      challenges that will require an increase in its complexity. We propose the need
      for engineered tissues that faithfully recapitulate their native structures to
      allow a greater understanding of tissue function, dysfunction, and potential
      therapeutic intervention.

PMID- 15963734
TI  - Serum immunoglobulin M in Atlantic halibut (Hippoglossus hippoglossus):
      characterisation of the molecule and its immunoreactivity.
AB  - Three preparations of purified immunoglobulin (IgM) were isolated from serum of
      Atlantic halibut (Hippoglossus hippoglossus) by means of three different methods,
      and each of the three IgM preparations was used to produce a polyclonal rabbit
      anti-halibut IgM antiserum. One of the IgM preparations was employed in the
      characterisation of halibut serum immunoglobulin. Halibut IgM was shown to
      consist of two subunits, compatible with heavy (mu) and light (L) chains. A
      single mu chain at approximately 76 kDa, and six possible molecular weight (MW)
      variants of L chain were found (range approximately 25 to approximately 28.5
      kDa). IgM was glycosylated on the heavy chain and N-linked carbohydrate
      constituted approximately 10.3% (w/w) of the total MW of IgM. The dominant form
      of non-reduced IgM had a MW of approximately 780 kDa, suggesting a tetrameric
      structure. Non-reduced IgM also showed a number of minor protein bands. Based on
      estimated MW, the relative carbohydrate content and the reactivity with all three
      anti-halibut IgM antisera, mono-, di- and trimeric redox forms of IgM were
      identified. The three antisera were characterised as to specificity and
      reactivity by means of enzyme linked immuno-sorbent assay (ELISA), crossed immuno
      electrophoresis (CIE), and immunoblotting methods. The antisera showed a
      considerable diversity in their specificity to the suggested MW variants of
      halibut Ig light chain. A method for immunohistochemical detection of IgM in
      tissue was established. Protein A or protein G affinity for the IgM was not
      detectable.

PMID- 15963735
TI  - Effects of fasting on evaluation of gastrointestinal transit with charcoal meal.
AB  - INTRODUCTION: At the present time, most studies investigating gastrointestinal
      transit time with charcoal are conducted in fasted rats. It seems reasonable to
      hypothesize that the fasting state of rats could influence the effect a compound
      had on gastrointestinal transit time. The purpose of this study was to
      investigate the effects of food on the pharmacological effects on
      gastrointestinal transit. METHODS: For each drug investigated, two sets of 32
      male Sprague-Dawley rats were used. One set was studied after being fasted for
      approximately 6 h, the second set was studied after free access to food. Each set
      had 4 groups of animals (n=8/group) that were administered different doses,
      allowing the assessment of the drug effect after fasting and after free access to
      food. Animals were administered 0, 10, 25, and 75 mg/kg of morphine; 0, 10, 20,
      and 40 mg/kg loperamide, or 0, 0.05, 0.5, and 3.0 mg/kg clonidine. At
      predetermined times, an activated charcoal suspension was administered by oral
      gavage. Thirty minutes after receiving the charcoal meal, rats were euthanized
      and the small intestine was removed. The length of the small intestine and the
      distance traveled by the charcoal were recorded. For each animal,
      gastrointestinal transit was calculated as the percentage of the distance
      traveled relative to the total length of the small intestine. RESULTS: Baseline
      (vehicle dosed animals) gastrointestinal transit was significantly greater in
      fasted versus fed rats. In fasted rats, morphine did not have a significant
      effect on transit. In fed rats, 25 and 75 mg/kg morphine caused a significant
      decrease in transit. In fed and fasted rats, 0.5 and 3 mg/kg clonidine caused a
      significant decrease in transit. Loperamide did not affect gastrointestinal
      transit in fed or fasted rats at doses up to 40 mg/kg. DISCUSSION: These data
      demonstrate that food does not reduce the sensitivity of the gastrointestinal
      transit time.

PMID- 15963736
TI  - Leupeptin-sensitive proteases involved in cell survival after X-ray irradiation
      in human RSa cells.
AB  - Proteases have received attention as important cellular components responsible
      for stress response in human cells. However, little is known about the role of
      proteases in the early steps of cell response after X-ray irradiation. In the
      present study, we first searched for proteases whose activity levels are changed
      soon after X-ray irradiation in human RSa cells with a high sensitivity to X-ray
      cell-killing. RSa cells showed an increased level of fibrinolytic protease
      activity within 10 min after irradiation with X-ray (up to 3 Gy). The induced
      protease activity was proved to be inhibited by leupeptin. We next examined
      whether this protease inducibility is related to the X-ray susceptibility of
      cells. Treatment of RSa cells with leupeptin prior to X-ray irradiation resulted
      in lowered colony survival and an increased ratio of G(2)/M-arrested cells and
      apoptotic cells. These results suggest that leupeptin-sensitive proteases are
      involved in the resistance of human RSa cells to X-ray cell-killing.

PMID- 15963737
TI  - Novel visual stimuli activate a population of neurons in the primate
      orbitofrontal cortex.
AB  - Neurons were found in the rhesus macaque anterior orbitofrontal cortex that
      respond to novel but not to familiar visual stimuli. Some of these neurons
      responded to all novel stimuli, and others to only a subset (e.g., to novel
      faces). The neurons have no responses to familiar reward- or punishment
      associated visual stimuli, nor to taste, olfactory or somatosensory inputs. The
      responses of the neurons typically habituated with repeated presentations of a
      novel stimulus, and five presentations each 1s was the median number for the
      response to reach half-maximal. The neurons did not respond to stimuli which had
      been novel and shown a few times on the previous day, indicating that the neurons
      were involved in long-term memory. The median latency of the neuronal responses
      was 120 ms. The median spontaneous firing rate was 1.3 spikes/s, and the median
      response to novel visual stimuli was 6.0 spikes/s. These findings indicate that
      the long-term memory for visual stimuli is information that is represented in a
      region of the primate anterior orbitofrontal cortex.

PMID- 15963738
TI  - Aortic calcification.
AB  - OBJECTIVES: Vascular calcification is a complicating factor observed in advanced
      atherosclerosis. This review summarises the present knowledge regarding abdominal
      aortic calcification. DESIGN: Literature review. METHODS: A literature review was
      carried using MEDLINE and PUBMED with the search terms 'abdominal', 'aortic' and
      'calcification'. Articles were assessed for data regarding mechanisms,
      measurement, risk factors and outcomes of aortic calcification. RESULTS: Thirty
      relevant studies were identified. These demonstrated a positive correlation
      between abdominal aortic calcification and the following factors: older age,
      hypertension, and smoking. Further studies are required to critically assess
      other risk factors such as gender, diabetes mellitus and renal failure.
      Calcification of the abdominal aorta is associated with an increased risk of
      mortality, coronary heart disease and stroke. CONCLUSION: Aortic calcification
      predicts an increased incidence of cardiovascular events, however, the reasons
      for this association requires further investigation. Accurate measurement of
      aortic calcification is likely to be increasingly used to determine the risk of
      cardiovascular events.

PMID- 15963739
TI  - Intermittent claudication: exercise-increased walking distance is not related to
      improved cardiopulmonary fitness.
AB  - OBJECTIVES: To assess if exercise training improves the symptoms of intermittent
      claudication by improvement in cardiopulmonary fitness. METHODS: Claudication
      distance (CD), maximum walking distance (MWD), calf endurance (repetitive heel
      raises), cardiovascular fitness (VO2 peak), and ankle-brachial pressure index
      (ABPI) were measured in 16 subjects with intermittent claudication before, and
      following an 8-week treadmill training programme. RESULTS: Training resulted in a
      median increase in CD of 65.5 m (p<0.01), MWD of 339.5 m (p<0.001) and HR of 19
      (p<0.03). Notably, improvements in MWD correlated with those in HR (p=0.001;
      R=0.75). There was no training-associated change in VO2 peak (median increase of
      only 0.35 ml/kg/min; p=0.60) or ABPI (median increase of only 0.01; p=0.64).
      CONCLUSION: In this study, overall improvement in claudication was not related to
      an improvement in cardiopulmonary fitness.

PMID- 15963740
TI  - Hand-assisted laparoscopic aortobifemoral bypass for occlusive disease. Early and
      mid-term results.
AB  - OBJECTIVES: To evaluate the early and mid-term results of hand-assisted
      laparoscopic surgery (HALS) for aorto-iliac reconstruction. DESIGN: Prospective
      survey. MATERIALS AND METHODS: Between February 2002 and January 2004, 46
      patients received an aortobifemoral bypass for advanced occlusive disease by
      HALS. RESULT: There was one conversion to open surgery. Mortality was 4.5%. The
      median return to solid oral diet took 36 h (24-182), the median hospital stay was
      5 days (3-26). Primary patency rate at 1 year was 97.5%. The incidence of
      incisional hernia was 19.5%. CONCLUSIONS: HALS aorto-iliac reconstruction should
      be considered as a minimal invasive technique with good early and mid-term
      results.

PMID- 15963741
TI  - Detection of abdominal aortic aneurysm in patients with peripheral artery
      disease.
AB  - OBJECTIVE: To describe the prevalence of abdominal aortic aneurysms (AAA) in
      patients with peripheral artery disease (PAD). DESIGN: Observational,
      descriptive, transverse study. PATIENTS AND METHODS: We performed an abdominal
      ultrasound in 1190 consecutive patients with lower limb chronic ischemia (1/99
      12/04). We registered cardiovascular risk factors and clinical data for analysis.
      RESULTS: The ultrasound was inconclusive in 24 (2%) patients; 1166 patients
      completed the study. They were mostly male (93.7%), with an age mean of 67+/-9.9
      years (37.7-93.4). The main cardiovascular risk factors were: smoking (80.9%),
      hypertension (41.7%) and hypercholesterolemia (31.4%). The prevalence of AAA was
      13% (n = 151). Only 1.5% (n = 17) of the patients had a large AAA (>5 cm). The
      AAA was clearly more prevalent in men (n = 148; 13.6%) than in women (n = 3;
      4.1%) (RR 3.47; 95% CI 1.11-10.89; p = 0.02). The prevalence significantly
      increased with age, with a maximum of 17.1% in over 75-year-old men (p = 0.006).
      Patients with tibial disease had a significantly higher prevalence of AAA than
      aortoiliac or femoro-popliteal disease (p = 0.02). CONCLUSIONS: The prevalence of
      AAA in patients with PAD is much higher than that reported in the general
      population. We recommend that an abdominal ultrasound be routinely included in
      the study of these patients. Over 75-year-old men are at particularly high-risk.

PMID- 15963742
TI  - Hyperhomocysteinaemia as a risk factor for deep-vein thrombosis.
AB  - OBJECTIVE: Several studies have shown a relation between hyperhomocysteinaemia
      and vascular disease. To assess the risk of deep-vein thrombosis (DVT) associated
      with hyperhomocysteinaemia, we studied plasma homocysteine levels in patients
      with deep-vein thrombosis and in normal control subjects. MATERIALS AND METHODS:
      We measured plasma homocysteine levels in 48 patients with deep-vein thrombosis
      and in 33 healthy controls matched to the patients according to age and sex.
      Plasma homocysteine levels were measured with high performance liquid
      chromatography and fluorescence detection. Hyperhomocysteinaemia was defined as a
      plasma homocysteine level about 15 micromol/L in both groups. The diagnosis of
      all patients with deep-vein thrombosis (n=48) was verified by Doppler
      ultrasonography. RESULTS: Plasma homocysteine levels were found to be increased
      in the deep-vein thrombosis group compared the control group (p<0.001, t-test).
      The mean plasma homocysteine level in the patients was 17.1 SD 5.13 micromol/L
      (range 6.4-31.3), and that in the controls was 9.0 SD 1.27 micromol/L (range 6.0
      11.5). The association between elevated homocysteine levels and venous thrombosis
      was stronger among men than among women. CONCLUSIONS: The increased plasma
      homocysteine levels we have observed may have a causative role in the development
      of deep-vein thrombosis.

PMID- 15963743
TI  - In-hospital operative mortality of ruptured abdominal aortic aneurysm: a
      population-based analysis of 5593 patients in The Netherlands over a 10-year
      period.
AB  - OBJECTIVE: To determine the operative mortality of ruptured abdominal aortic
      aneurysm (RAAA) in The Netherlands. DESIGN: Retrospective population-based study
      of nation-wide in-hospital mortality of RAAA repair. METHODS: Data were obtained
      from a national registry for medical diagnosis and procedures. In-hospital
      mortality of RAAA repair, defined as death during hospital admission irrespective
      of the cause of death, was determined in the period 1991-2000. Variables of
      potential influence on in-hospital mortality, including age, gender, date of
      surgery and hospital type (0-399 beds, > or =400 beds or university hospitals)
      were studied in a multivariate analysis. RESULTS: The overall in-hospital
      mortality of RAAA repair in 5593 patients in the 10-year period was 41% (95%
      confidence interval: 40-42%). In the multivariate analysis, age and hospital type
      were the most important independent predictors for in-hospital mortality. Gender,
      year and season of surgery could not be identified as significant risk factors.
      CONCLUSIONS: Over a recent decade, in-hospital mortality of RAAA repair remained
      unchanged at 41%. Age and hospital class were the most important independent risk
      factors.

PMID- 15963744
TI  - Identification of patients at risk for ischaemic cerebral complications after
      carotid endarterectomy with TCD monitoring.
AB  - OBJECTIVES: Transcranial Doppler (TCD) monitoring for micro embolic signals
      (MES), directly after carotid endarterectomy (CEA) may identify patients at risk
      of developing ischaemic complications. In this retrospective multicentre study,
      this hypothesis was investigated. METHODS: Centres that monitored for MES after
      CEA were identified by searching Medline. Individual patient data were obtained
      from centres willing to collaborate. The number of emboli in 1h was computed. Uni
      and multivariate logistic regression analyses were performed for the variables
      gender, age and number of MES. Discriminative ability of MES monitoring was
      investigated in a ROC curve. RESULTS: Nine hundred and ninety-one patients were
      monitored in the first 3h after CEA. Two percent developed ischaemic cerebral
      complications. Univariate analysis revealed statistically significant
      associations between ischaemic cerebral complications and both gender and MES,
      but not age. In a multivariate analysis, > or =8 MES/h showed a statistically
      significant relationship with cerebral complications (OR 8.1, 95% CI 1.8-36), in
      contrast to gender (OR 2.2, 95% CI 0.9-5.5). The ROC curve yielded an AUC of 0.83
      for monitoring of MES. CONCLUSIONS: These results support the use of TCD
      monitoring for MES shortly after CEA in order to identify patients at risk of
      developing ischaemic cerebral complications.

PMID- 15963745
TI  - Iatrogenic femoropopliteal graft entrapment leading to thrombus formation.
AB  - Femoropopliteal bypass graft entrapment by the gastrocnemius muscle and tendons
      is an unusual cause of graft stenosis or thrombosis. Before graft occlusion
      occurs, reduced flow may be seen either with the knee in extension or
      hyperextension or by passive dorsiflexion of the ankle. We report a case of a
      femoropopliteal bypass graft entrapment causing a thrombus in the distal graft.
      Duplex imaging, angiography, MRI and graft surveillance programs are useful
      diagnostic tools. Treatment options include dividing the occluding muscles and
      tendons and rerouting the graft.

PMID- 15963746
TI  - The effects of hydroxyethyl starch compared with gelofusine on activated
      endothelium and the systemic inflammatory response following aortic aneurysm
      repair.
AB  - OBJECTIVE: To investigate the effect of HES, used as a plasma volume expander, on
      endothelial cell activation induced by ischaemia-reperfusion in humans. MATERIAL
      AND METHODS: Forty patients undergoing elective infrarenal aneurysm repair were
      randomised to receive either gelatine or hydroxyethyl starch solution as plasma
      expanders. The anaesthetic technique was standardised. All patients received the
      same crystalloid as per standard protocol. Urine samples and blood samples were
      collected at various times for assessment of microalbuminuria and von Willebrand
      factor (vWf) and CRP. RESULTS: The peak C-reactive protein was significantly
      lower in the patients treated with HES than those treated with gelofusine [142
      mg/L (113,196 mg/L) vs 246 mg/L (189,291 mg/L) mg/L, P < 0.01, Mann-Whitney
      test]. The peak ACR was also significantly lower in the HES treated patients (9.3
      mg/mmol vs 23.3 mg/mmol, P < 0.05). The plasma level of vWf was significantly
      higher in the gelofusine treated patients than those treated with HES [173.5 U/dl
      Vs 80.5 U/dl, P < 0.001, at 4 hr; 160 U/dl Vs 82.5 U/dl, P < 0.001, at 8 hr; 191
      U/dl Vs 100.5 U/dl, P < 0.001, at 12 hr; 209 U/dl Vs 81.0 U/dl, P < 0.001, at 24
      hr]. CONCLUSION: HES may damp down the systemic inflammatory response and reduce
      endothelial cell dysfunction.

PMID- 15963748
TI  - The major allele of the alanine:glyoxylate aminotransferase gene: nine novel
      mutations and polymorphisms associated with primary hyperoxaluria type 1.
AB  - We describe nine novel mutations and polymorphisms occurring on the major allele
      of the human alanine:glyoxylate aminotransferase gene in patients with primary
      hyperoxaluria type 1, an autosomal recessive disease resulting from a deficiency
      of the liver peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT; EC
      2.6.1.44). The PH1 mutations include two small frameshift mutations, 327delG and
      117_118insCA, a large deletion spanning exon 9 and portions of the flanking
      introns, a splice junction mutation, IVS6+5G>C, and two missense mutations, G161R
      and S218L. Expression studies of the two missense mutations indicated very little
      enzymatic activity associated with either of them. Three polymorphisms in the
      coding sequence were also identified, I279T, A280V, and T235T. Expression studies
      of I279T and A280V suggested essentially normal AGT activity. I279T, found in two
      cases, was located on a 33_34insC allele. A280V and T235T were both located on
      the same allele as IVS6+5G>C. We have also identified recurrences of previously
      reported rare mutations, 33delC, IVS7-1G>C, and IVS4-1G>A. Five of the six novel
      PH1 mutations occurred in a compound heterozygous state with either of two common
      PH1 mutations, G170R or 33_34insC. S218L was apparently homozygous in two
      individuals. These findings contribute to our overall picture of heterogeneity of
      mutations in PH1 and the AGT major allele.

PMID- 15963747
TI  - Mitochondrial energy metabolism is markedly impaired by D-2-hydroxyglutaric acid
      in rat tissues.
AB  - Tissue accumulation of high amounts of D-2-hydroxyglutaric acid (DGA) and l-2
      hydroxyglutaric acid (LGA) is the biochemical hallmark of the inherited
      neurometabolic disorders D-2-hydroxyglutaric aciduria (DHGA) and l-2
      hydroxyglutaric aciduria (LHGA), respectively. Patients affected by DHGA
      predominantly present neurological and cardiomuscular symptoms, while those with
      LHGA have mainly severe neurological symptoms. Lactic aciduria and/or lactic
      acidemia may also occur in both disorders, suggesting mitochondrial dysfunction.
      We have previously reported that cytochrome c oxidase (COX) activity is severely
      inhibited by DGA in rat cerebral cortex and human skeletal muscle. In the present
      study, we initially evaluated the role of DGA and LGA on the mitochondrial
      respiratory chain complex activities, as well as CO2 on production in cardiac and
      skeletal muscle from 30-day-old Wistar rats. DGA significantly inhibited COX and
      ATP synthase (F0F1-ATP synthase) activities, in contrast to the other activities
      of the respiratory chain enzymes which were not affected by DGA in both muscular
      tissues. In addition, CO2 production was also markedly reduced by DGA in rat
      skeletal and cardiac muscles. On the other hand, LGA did not interfere with any
      of the respiratory chain complex activities studied, neither with CO2 generation.
      We also measured mitochondrial respiratory parameters in rat brain mitochondrial
      preparations in the presence of DGA and LGA. Both metabolites significantly
      lowered the respiratory control ratio in the presence of glutamate/malate and
      succinate. Since the metabolites stimulated oxygen consumption in state IV and
      compromised ATP formation, it can be presumed that these organic acids might act
      as endogenous uncouplers of mitochondria respiration. Moreover, COX activity
      linked to TMPD-ascorbate was significantly reduced by DGA in the brain
      mitochondrial enriched fractions. Finally, DGA and LGA reduced cell viability of
      rat cerebral cortex slices, as determined by the MTT assay. In case our in vitro
      data also occur in vivo, it may be presumed that impairment of energy metabolism
      may contribute to the understanding of the clinical features mainly of patients
      affected by DHGA.

PMID- 15963749
TI  - [Epidemiological surveillance of blood donors and residual risk of blood-borne
      infections in France, 2001 to 2003].
AB  - The national surveillance of French blood donors is performed by the Institut de
      Veille Sanitaire and the National Reference Center for Hepatitis B and C in
      transfusion in collaboration with the Etablissement Francais du Sang and the Army
      blood center. The main objectives of this surveillance are to evaluate trends in
      prevalence and incidence rates of blood-borne infections in the blood donor
      population, to identify routes of contamination and to assess residual risk. This
      exhaustive surveillance also contributes to evaluate the blood donor selection
      and the impact of measures taken to prevent infections in the general population.
      The analyse of the database of all blood donations obtained from 2001 to 2003 has
      shown that prevalence rates were stable in the study period (0.60 per 10(4)
      donors for HIV, 8.0 per 10(4) donors for HCV, 1.8 per 10(4) first-time donors for
      HBs Ag and 0.56 per 10(4) donors for HTLV), The incidence rate of HIV and HBV (1
      per 10(5) person-years) was three-times higher than for HCV (0.35 per 10(5)
      person-years) and eleven times higher than for HTLV (0.09 per 10(5) person
      years). At least, the residual risk of transfusion-transmitted viral infections
      is very low: 1/3,150,000 donations for HIV, 1/10,000,000 donations for HCV and
      1/640,000 donations for HBV. The yield of Nucleic Acid Testing (NAT) is limited
      since only 2 donations for HIV and 3 for HCV which were negative for antibodies
      were discarded thank to the NAT.

PMID- 15963750
TI  - [Stating technical requirements and deferral criteria for whole blood donation].
AB  - Blood donation is framed by regulations whose finality is to guarantee the safety
      of blood transfusions and to preserve the health of the donors. Each blood
      donation is preceded by a medical interview which evaluates the aptitude of the
      donor to support a 400 to 600 mL collection of blood or its components, and
      checks the absence of exposure to blood-borne diseases. The criteria of exclusion
      of blood donation are defined on clinical and epidemiologic arguments. The aim of
      blood donors selection is consisting in managing the residual infectious risk
      caused by known pathogens, risk related to the window period due to recent
      contaminations, the absence of technique of pathogens inactivation available for
      the cellular blood products, and the risk inherent in any production process.
      Blood donors selection proved to be the only means of reducing the risk of
      transmission of an emergent agent by blood transfusion.

PMID- 15963751
TI  - A new method for accurate and fast measurement of 3D eye movements.
AB  - Videooculography (VOG) is an eye movement measurement method used in the
      objective evaluation of vestibulo-ocular reflexes (VOR). An important requirement
      of VOG is to accurately estimate pupil center and ocular torsion, irrespective of
      drooping eyelids, eyelashes, corneal reflection, and blinking. Finding the
      accurate center of the pupil is particularly important in three-dimensional VOG,
      since otherwise, significant errors can occur in measuring torsional eye
      movement. A fast algorithm was proposed to accurately ascertain the pupil center,
      in spite of the complicating factors mentioned above. In this study, real-time
      three-dimensional VOG, which can measure horizontal, vertical, and torsional eye
      movements and calculate the pupil radius, was implemented using the proposed
      method. When the pupil radius was determined, the vertical position was measured
      within an error margin of less than 3%, even though only 10% of the pupil was
      visible. The time required to measure both three-dimensional eye movements and
      the pupil radius was less than 16 ms. Thus, eye movements can be measured in real
      time. The resolutions of horizontal, vertical, and torsional eye movement were
      0.2 degrees, 0.2 degrees, and 0.1 degrees, respectively, with maximum ranges of
      +/- 35 degrees, +/- 25 degrees, and +/- 18 degrees.

PMID- 15963752
TI  - Mechanics of crawling cells.
AB  - Crawling of keratocytes derived from aquatic vertebrates represents a very useful
      model system for the investigation of cell locomotion because of its ease of
      handling and the clear structural separation of a thin cytoplasmic layer, the
      lamella, from the cell body containing the nucleus and other organelles.
      Spreading of spherical keratocytes results in fried egg shaped cells, which on
      withdrawing their lamella at one side become polarized and start moving.
      Hydrostatic pressure, tension at the cortex, traction forces exerted on the
      adhesion sites and inside the cells along filamentous structures are required to
      gain a certain shape. Traction forces have been made visible using scanning
      acoustic microscopy. This method also allowed for the demonstration of
      cytoplasmic fluxes inside a moving keratocyte and changes of forces while a
      migrating cell is changing its direction of locomotion. The pros and cons for
      actin polymerization at the leading front providing the driving force for
      crawling are discussed on the basis of structural and experimental results: do
      they stringently identify polymerization of actin as the only driving machinery.
      Such a mechanism not only should explain the advancement of the leading edge but
      also the movement of the whole cell, i.e. the material flux taking place from the
      cell body to the periphery. Even if the lamella periphery itself may be motile by
      actin turnover this scheme may represent an oversimplification if applied to the
      whole cell. Considering the complexity of a whole cell simplifying model systems
      may not lead to adequate descriptions of the mechanisms as they occur within
      cells with a highly complex structure, although the model might be consistent and
      sufficient to describe, i.e. crawling in general.

PMID- 15963753
TI  - Increased writing activity in Parkinson's disease: a punding-like behavior?
AB  - We report a 32-year-old male patient with early-onset Parkinson's disease who
      exhibited abnormally increased writing activity. The patient displayed a
      disabling and pronounced increased writing activity, filling up to 10 pages or
      more per day in a notebook, and spending more than 12 h writing. In general,
      there was not much meaning in most of the writing, though there was a particular
      preference in tabulating the names of various sport and TV personalities. The
      writing activity gradually diminished following treatment with quetiapine
      hydrochloride, an anti-psychotic agent, at 25 mg/day. Although the
      pathophysiological mechanism underlying the increased writing is unclear, we
      believe it should be regarded as a form of punding or stereotyped behavior that
      has been suggested to be associated with dopaminergic therapy in Parkinson's
      disease.

PMID- 15963754
TI  - Dendritic cell trafficking: more than just chemokines.
AB  - Dendritic cells (DC) are professional antigen presenting cells. To accomplish
      their biological function they need to undergo a complex pattern of migration
      which includes their localization to both peripheral non-lymphoid tissues and
      secondary lymphoid organs. In the absence of correct tissue localization, DC fail
      to promote proper immune responses. The first description of chemotactic factors
      active on DC was published by this group 10 years ago. Since then, it was
      described that multiple signals are able to regulate the migration of DC in vitro
      and in vivo. These signals include nonchemokine chemotactic agonists, lipid
      mediators and membrane proteins. This review summarizes this large body of
      information and focuses on the complexity of the process of DC trafficking.

PMID- 15963755
TI  - Piecewise affine registration of biological images for volume reconstruction.
AB  - This manuscript tackles the reconstruction of 3-D volumes via mono-modal
      registration of series of 2-D biological images (histological sections,
      autoradiographs, cryosections, etc.). The process of acquiring these images
      typically induces composite transformations that we model as a number of rigid or
      affine local transformations embedded in an elastic one. We propose a
      registration approach closely derived from this model. Given a pair of input
      images, we first compute a dense similarity field between them with a block
      matching algorithm. We use as a similarity measure an extension of the classical
      correlation coefficient that improves the consistency of the field. A
      hierarchical clustering algorithm then automatically partitions the field into a
      number of classes from which we extract independent pairs of sub-images. Our
      clustering algorithm relies on the Earth mover's distribution metric and is
      additionally guided by robust least-square estimation of the transformations
      associated with each cluster. Finally, the pairs of sub-images are,
      independently, affinely registered and a hybrid affine/non-linear interpolation
      scheme is used to compose the output registered image. We investigate the
      behavior of our approach on several batches of histological data and discuss its
      sensitivity to parameters and noise.

PMID- 15963756
TI  - Photoelectron spectroscopy of free radicals: 4-methyl-sulfonyloxy-TEMPO.
AB  - HeI and HeII photoelectron spectra of persistent free radical: 2,2,6,6
      tetramethyl-4-(methylsulfonyloxy)piperidinyl-1-oxide (CH3SO3-TEMPO) have been
      measured. The analysis of the electronic structure is based on comparison with
      the spectra of related radicals and with DFT calculations. The electronic
      structure of the nitroxide group in the title radical seems unaffected by the
      presence of substituent group. This is consistent with results observed for other
      nitroxide radicals and with the electrochemical oxidation potentials.

PMID- 15963757
TI  - Internet use by a referral gastroenterology clinic population and their medical
      information preferences.
AB  - BACKGROUND: Internet use is growing rapidly in Iran. However, little is known
      about the rate of Internet access and Internet use habits of gastroenterology
      patients and their health information preferences in the country. METHODS: A two
      part questionnaire was presented to a convenience sample of 401 consecutive
      outpatients (mean age: 43.7 years) of a referral gastroenterology clinic in
      Tehran from February 21 to March 13, 2004. RESULTS: Of all literate patients
      (92%), 62% self-estimated their disease-related knowledge as nothing to little.
      The most common sources of information were media (62%) and printed materials
      (58%). Printed material (57%) and media (35%) were the most preferred means of
      receiving health information; the Internet was the most preferred means among
      Internet users and almost all of them were interested in getting online medical
      services. The cause (65%) and treatment (56%) of disease were the most favorite
      knowledge topics. Of all patients 28% could use Internet. Males, more educated
      and younger subjects were more likely to use the Internet. Of the Internet users,
      37% had already performed at least one search for medical information.
      CONCLUSION: Though Internet is not yet a popular means of patient education in
      Iran, considering the speedy growth of Internet use and its undeniable advantages
      and prospects in a young country like Iran, it seems wise for private and public
      health sectors to start more vigorous planning to develop web-based patient
      education systems run by trusted bodies and encourage and cultivate its use among
      patients.

PMID- 15963758
TI  - C77G mutation in protein tyrosine phosphatase CD45 gene and autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a rare frequent, multiplex disorder with undefined
      etiology. Susceptibility to autoimmune hepatitis results from complex
      interactions between genetic and environmental factors. In this study, we
      investigated the involvement of C77G mutation in CD45 gene in patients with
      autoimmune hepatitis among Iranian population by genotyping this mutation in 70
      patients and 140 healthy individuals. METHODS: : After amplifying exon 4 by
      Polymerase chain reaction, we genotyped this mutation with MspI restriction
      endonuclease among the studied population. RESULTS: : None of the cases with AIH
      was hetero or homozygote for C77G mutation. Controls had normal genotype except
      one of them who was heterozygote for C77G mutation. CONCLUSION: : Our results do
      not confirm the genetic link between C77G mutation and autoimmune hepatitis in
      Iranian population.

PMID- 15963759
TI  - Phosphoinositide 3-kinases as drug targets in cancer.
AB  - The past two years have seen phosphoinositide 3-kinases (PI3Ks) move from being
      seen as potential targets for chemotherapeutics, to one of them--PI3Kalpha--being
      generally accepted as validated. A huge amount of work indicated that there was
      an important role for PI3Ks in tumour progression and, particularly, in the
      control of proliferation, survival and regulation of the potential oncogene PKB.
      These links were further strengthened by studies showing that the tumour
      suppressor, PTEN, is an antagonist of PI3K signalling and that somatic mutations
      of p110alpha (PIK3CA) are present in a variety of cancers. We now know that three
      of the most frequent mutations in cancer constitutively activate PI3Kalpha and,
      when expressed in cells, they drive the oncogenic transformation and chronic
      activation of downstream signalling by molecules such as PKB, S6K and 4E bp1 that
      is commonly seen in cancer cells. A large body of research into the cellular
      roles of PI3Ks has also further validated them as potential foci for cancer
      chemotherapy, with several additional PI3K effectors controlling cell
      proliferation and apoptosis having been described. Furthermore, molecules
      important to the processes of metastasis, development of multi-drug resistance,
      the 'Warburg effect', angiogenesis and cell growth (i.e. distinct to
      proliferation) have been found to depend upon, or to be driven by, PI3K activity.

PMID- 15963760
TI  - Promoting apoptosis in disease management: a panacea or Trojan horse?
AB  - In our enthusiasm to advocate apoptosis as a therapeutic strategy for the
      management of disease we need to be mindful that the clearance of apoptotic cells
      is itself immunomodulatory and that it may not always be as benign or beneficial
      as we think. Indeed, the existence of free apoptotic cells in situ may
      potentially be pathological, and not necessarily physiological, and any attempt
      to promote apoptosis in the absence of an appropriate phagocytic response for the
      treatment of, for example, inflammation or cancer might exacerbate or initiate an
      autoimmune pathology.

PMID- 15963761
TI  - RETRACTED: Molecular basis of AMD: current concepts and recent advances.
AB  - This article, which was originally commissioned from Dr. Ambati, but submitted by
      corresponding author Dr. Anand, has been permanently retracted at the request of
      the Editor due to an irreconcilable dispute regarding authorship. Dr. Ambati
      refutes authorship and does not want his name associated with the article.
      (Please note that in the original publication Dr. Ambati's name was mis-spelt.).

PMID- 15963762
TI  - Humoral autoimmunity in mice overexpressing B cell surface CD19: vital role for
      MHC class II.
AB  - B6 mice bearing a transgene (Tg) for human CD19 (hCD19) harbor increased numbers
      of splenic Ig-secreting cells (IgSC), increased serum levels of total Ig and
      autoantibodies, but decreased numbers of splenic B cells. To assess the influence
      of MHC class II (MHCII) to this phenotype, MHCII-deficient CD19-Tg mice were
      generated. Compared to MHCII-sufficient CD19-Tg mice, splenic IgSC numbers and
      serum Ig and autoantibody levels were markedly diminished, and the decrease in
      splenic B cell numbers was aggravated. Remarkably, genetic reconstitution of
      these MHCII-deficient mice with a human DQ8 Tg resulted in a hierarchical
      restorative pattern. Restoration of splenic B cell numbers was complete;
      restoration of numbers of splenic IgSC and of serum Ig levels was partial; and
      restoration of circulating autoantibody levels was virtually non-existent. Thus,
      MHCII expression has a profound effect on B cells which can be uncoupled from
      global Ig and autoantibody production in the hCD19-Tg model. This raises the
      possibility that MHCII affects B cells in a manner that, at least in part, is
      independent of helper T cell function.

PMID- 15963763
TI  - Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by
      lipo- and polyplexes.
AB  - We investigated the effects of inhibitors of clathrin-mediated endocytosis
      (chlorpromazine and K(+) depletion) and of caveolae-mediated uptake (filipin and
      genistein) on internalization of FITC-poly-l-lysine-labeled DOTAP/DNA lipoplexes
      and PEI/DNA polyplexes by A549 pneumocytes and HeLa cells and on the transfection
      efficiencies of these complexes with the luciferase gene. Uptake of the complexes
      was assayed by fluorescence-activated cell sorting. Lipoplex internalization was
      inhibited by chlorpromazine and K(+) depletion but unaffected by filipin and
      genistein. In contrast, polyplex internalization was inhibited by all four
      inhibitors. We conclude that lipoplex uptake proceeds only by clathrin-mediated
      endocytosis, while polyplexes are taken up by two mechanisms, one involving
      caveolae and the other clathrin-coated pits. Transfection by lipoplexes was
      entirely abolished by blocking clathrin-mediated endocytosis, whereas inhibition
      of the caveolae pathway had no effect. By contrast, transfection mediated by
      polyplexes was completely blocked by genistein and filipin but was unaffected by
      inhibitors of clathrin-mediated endocytosis. Fluorescence colocalization studies
      with a lysosomal marker, AlexaFluor-dextran, revealed that polyplexes taken up by
      clathrin-mediated endocytosis are targeted to the lysosomal compartment for
      degradation, while the polyplexes internalized via caveolae escape this
      compartment, permitting efficient transfection.

PMID- 15963764
TI  - Influence of organic selenium on hsp70 response of heat-stressed and
      enteropathogenic Escherichia coli-challenged broiler chickens (Gallus gallus).
AB  - The effect of dietary selenium yeast, a source of organic selenium, on heat shock
      protein 70 (hsp70) responses, redox status, growth and feed utilization were
      evaluated either in enteropathogenic Escherichia coli-challenged (EPEC) or in
      heat-stressed (HS) male broiler chickens grown to 42 days of age. One day-old
      chicks in experiment 1 were challenged orally with EPEC (10(6) cfu/chicken on day
      1 and boosted by water application on days 2, 3, and 4) and fed diets with or
      without selenium yeast. Body weight (BW), feed conversion ratio (FCR), and total
      mortality were determined at 42 days of age, and this was followed by collection
      of ileal tissue for the quantification of total glutathione (TGSH), reduced
      glutathione (GSH), oxidized glutathione (GSSG), and hsp70 in randomly selected
      chickens from each treatment. In experiment 2, male broiler chickens were fed
      diets with or without selenium yeast under a thermoneutral rearing condition. At
      four weeks of age, blood and hepatic tissue were collected from chickens
      maintained in the thermoneutral environment and from chickens subjected to HS (40
      degrees C for 1 h) and analyzed for TGSH, GSH, GSSG, and hsp70. Selenium yeast
      improved BW, FCR, and decreased mortality in both control and EPEC-challenged
      chicks. Selenium yeast significantly attenuated hsp70 expression in EPEC
      challenged chickens and in those subjected to HS. The EPEC challenge increased
      TGSH and GSSG levels and decreased GSH/GSSG ratio. However, GSSG level
      accumulated in chickens fed diets without selenium supplementation resulting in a
      lower GSH/GSSG ratio in the selenium yeast-fed group. Heat stress increased GSSG
      level and decreased GSH/GSSG ratio. Selenium yeast-fed groups maintained higher
      levels of GSSG before and after HS with a resultant lower GSH/GSSG ratio. The
      hsp70 response was significantly less in those chickens fed selenium yeast and
      challenged with either EPEC or HS than in those chickens given no supplemental
      selenium. The results of this study suggest that selenium yeast supplementation
      had imparted resistance to oxidative stress associated with enteric bacteria
      infection and to high temperature exposure. It is believed that the resistance to
      the stressors was due to an improved redox status of the selenium yeast-fed
      chickens.

PMID- 15963765
TI  - A machine learning perspective on the development of clinical decision support
      systems utilizing mass spectra of blood samples.
AB  - Currently, the best way to reduce the mortality of cancer is to detect and treat
      it in the earliest stages. Technological advances in genomics and proteomics have
      opened a new realm of methods for early detection that show potential to overcome
      the drawbacks of current strategies. In particular, pattern analysis of mass
      spectra of blood samples has attracted attention as an approach to early
      detection of cancer. Mass spectrometry provides rapid and precise measurements of
      the sizes and relative abundances of the proteins present in a complex
      biological/chemical mixture. This article presents a review of the development of
      clinical decision support systems using mass spectrometry from a machine learning
      perspective. The literature is reviewed in an explicit machine learning
      framework, the components of which are preprocessing, feature extraction, feature
      selection, classifier training, and evaluation.

PMID- 15963766
TI  - Characterization and expression of two matrix metalloproteinase genes during sea
      urchin development.
AB  - Matrix metalloproteinases (MMPs) play an essential role in a variety of processes
      in development that require extracellular matrix remodeling and degradation. In
      this study, we characterize two MMPs from the sea urchin Strongylocentrotus
      purpuratus. These clones can both be identified as MMPs based on the presence of
      conserved domains such as the cysteine switch, zinc-binding, and hemopexin
      domains. In addition, both of these genes contain consensus furin cleavage sites
      and putative transmembrane domains, classifying them as membrane-type MMPs. We
      have named these clones SpMMP14 and SpMMP16 based on the vertebrate MMPs with
      which they share the greatest similarity. SpMMP14 is expressed in all cells from
      the egg to mesenchyme blastula stage embryo. Expression of this gene is strongest
      in the animal and vegetal poles early in gastrulation and in the animal pole only
      later in gastrulation. SpMMP16 is expressed at low levels in eggs. Expression of
      SpMMP16 becomes more pronounced in the vegetal pole region at the blastula and
      mesenchyme blastula stages and becomes confined to vegetal pole descendants, such
      as pigment cells, later in development. In the future, we hope to learn more
      about the possible functions of these genes in sea urchin development.

PMID- 15963767
TI  - Expression of Fgf and Tgfbeta signaling related genes during embryonic
      endochondral ossification.
AB  - Disturbed fibroblast growth factor (Fgf) and transforming growth factor beta
      (Tgfbeta) signaling lead to a variety of human skeletal disorders. To reveal the
      possible function and interaction of these signaling systems we have started to
      analyze the expression patterns of signaling factors, antagonists, receptors and
      transducers of these pathways in forelimbs of mouse embryos and compared them to
      the expression of established markers including Ihh. In addition to defining
      their expression domains in the developing bone, our study identified new
      subpopulations of chondrocytes characterized by the expression of distinct
      combinations of markers.

PMID- 15963768
TI  - LKB1/PAR4 protein is asymmetrically localized in mouse oocytes and associates
      with meiotic spindle.
AB  - The mouse secondary oocyte is polarized at the ultrastructural and molecular
      level, but very little is known about mechanisms involved in the establishment of
      this polarity. We showed that the LKB1 kinase, a mouse homologue of
      Caenorhabditis elegans PAR4 protein is asymmetrically localized to the animal
      pole of the mouse oocyte and during oocyte maturation associates with the
      microtubules of metaphase I and metaphase II meiotic spindles. Therefore, we
      suggest that LKB1/PAR4 protein, may participate in the polarization of the oocyte
      and in the regulation of the asymmetry of meiotic divisions during mouse
      oogenesis.

PMID- 15963769
TI  - Irx3 is differentially up-regulated in female gonads during sex determination.
AB  - Irx3 is a member of the Iroquois homeobox gene family that encodes a protein
      known for its essential role in spinal cord development. Transcript screening of
      male and female gonads during the critical period of sex determination (E12-13.5)
      revealed a sexually dimorphic expression pattern for Irx3 with female gonads
      exhibiting a sixfold increase in expression over time. Whole mount in situ
      hybridization confirmed the sexually dimorphic nature of Irx3 expression and
      immunohistochemical analysis of gonads at E13.5 determined that IRX3 and GATA4
      proteins co-localized to somatic cells of XX gonads. The Irx3 signal persisted in
      germ cell-depleted XX gonads resulting from Busulfan treatment suggesting that
      its expression was independent of germ cell regulation. Quantitative real-time
      PCR analysis over an extended time course determined that Irx3 message was low
      initially and then increased in XX gonads until E13.5, remained elevated until
      birth, diminished shortly after birth, and remained low in the adult ovary. In
      contrast, Irx3 message was 50% lower in male compared to female gonads at the
      initial time point, and continued to decrease over time. Further analysis of
      adult ovaries suggested that IRX3 expression is not present in any subpopulations
      of cells of the differentiated ovary. Together, these results suggest that the
      Irx3 signal is restricted to the somatic cell component of XX gonads and is
      present at a discreet period of ovarian development that ends abruptly at birth.
      This timing coincides with the transition of female primordial germ cells from
      mitotic proliferation to meiotic division, and the organization of germ cell
      cysts prior to primordial follicle development at birth.

PMID- 15963770
TI  - Overrepresentation of immunostimulatory CpG motifs in Burkholderia genomes.
AB  - Pulmonary infections with Burkholderia cepacia complex organisms contribute
      significantly to morbidity and mortality in patients with cystic fibrosis (CF),
      partially due to the intense inflammatory response of the host to the presence of
      bacteria and their byproducts. In the present study we show that Burkholderia
      genomes contain a large number of immunostimulatory CpG motifs. This is mainly
      because of their large genome size. This suggests that DNA from Burkholderia sp.
      has the potential to cause significant inflammatory response. Whether this
      contributes significantly to the airway inflammation often observed in infected
      CF patients remains to be determined.

PMID- 15963771
TI  - Monitoring the lung periphery of transplanted lungs.
AB  - Lung transplantation is now accepted as a viable therapeutic option for patients
      with end-stage lung diseases, but long-term survival is threatened by
      bronchiolitis obliterans (BO), which is regarded as a manifestation of chronic
      allograft rejection. We have used studies of ventilation distribution for the
      early detection of this complication. In a prospective study of 57 bilateral-lung
      transplant recipients, we showed that the slope of phase III of the helium single
      breath washout, which targets inhomogeneities of ventilation distribution in the
      terminal and respiratory bronchioles, was particularly sensitive to the
      development of BO. In a preliminary study using nitrogen multiple-breath
      washouts, we showed that S(acin) and S(cond), which reflect structural changes in
      the acinar and conductive lung zones, were both markedly increased in patients
      with BO. Taken together, these studies demonstrate that monitoring the function
      of the allograft by measuring the distribution of ventilation in the lung
      periphery may be a clinically valuable tool.

PMID- 15963772
TI  - Overweight and stunting in migrant Hispanic children in the USA.
AB  - In order to evaluate the need for preventive interventions to improve nutrition,
      the BMI/sex/age percentile, height/sex/age percentile, prevalence of stunting, at
      risk-for-overweight and overweight in a group of migrant Hispanic children, aged
      2-18, in southern New Jersey, USA, was assessed using anthropometric measurements
      of height, weight and skinfold thickness with reference to the NHANES 1999-2000.
      Results showed that the frequency of overweight in this sample--20%--exceeds that
      of the general U.S. pediatric population and equals or exceeds (in 2-5-year olds)
      that of settled Mexican-Americans. Being born in the U.S. significantly
      diminished the prevalence of stunting, especially in boys. The children of
      migrant Hispanic agricultural workers belong to a marginalized, poor and insecure
      population who are not included in the National Health and Nutrition Examination
      studies, because of their transience. This is the first anthropometric study to
      evaluate growth in this population in over 20 years.

PMID- 15963773
TI  - Crystallization of bacteriorhodopsin solubilized by a tripod amphiphile.
AB  - Bacteriorhodopsin (bR) is solubilized efficiently as a monomer by a novel
      surfactant, a tripod amphiphile (TPA), which permits the formation of purple
      hexagonal bR crystals under several conditions. The crystals, although small,
      diffract to 2.5 A resolution using synchrotron radiation. TPA may be useful for
      the solubilization, purification, and crystallization of other membrane proteins.

PMID- 15963774
TI  - Tissue and plasma kallikrein in inflammatory bowel disease.

PMID- 15963775
TI  - Physical function is impaired but quality of life preserved in patients with
      fibrous dysplasia of bone.
AB  - Fibrous dysplasia of bone (FD) is a congenital, non-heritable skeletal disorder
      that is associated with multiple skeletal complications, including repeated
      fractures, limb length discrepancy, and bone pain. The disease-specific impact of
      FD on quality of life outcomes is unknown. We sought to understand the impact of
      the scope and extent of the skeletal disease on quality of life in adults and
      children with FD. The health-related quality of life was quantified in a
      population of adults (n = 56) and children (n = 22) with FD using validated
      health assessment questionnaires, the Medical Outcomes Study 36 Item Short-Form
      Health Survey, volume 2 (SF36) (adults) and the Child Health Questionnaire Parent
      Form 50 (CHQ-PF50) (children). Clinical demographic data and skeletal disease
      burden scores (SDBS, amount of skeleton involved with FD) were measured, and
      correlations with health-related quality of life were sought. The SF36 and CHQ
      PF50 revealed lower Physical Function Summary scores in FD patients compared to
      the U.S. population norms (adult 41 vs. 50, Z score < -5.0, pediatric 39 vs. 50,
      Z score < -5.0). However, the SF36 and CHQ-PF50 Mental/Psychological summary
      scores were not different from those of U.S. population norms (adult 50 vs. 50, Z
      score = 0, pediatric 48 vs. 50 Z score = -0.9). The score on the Physical
      Function Domain of both tools was strongly negatively associated with the SDBS
      (adult Spearman rho = -0.43, P = 0.009, pediatric Spearman rho = -0.72, P =
      0.005). The groups of adult and pediatric patients with SDBS > 30 had decreased
      Physical Function Domain scores when compared to those with scores < 30 (adult 35
      vs. 45, P = 0.002, pediatric 57 vs. 78, P = 0.04, respectively). One of the
      largest effects was seen in the parents of children with FD, who had
      significantly lower Parental Emotional scores than those of the parents of
      healthy norms (54 vs. 88, Z score < -5.0), suggesting a high degree of emotional
      morbidity in the parents of children with FD. Despite measurable functional
      limitations in adults and children, and significant parental emotional
      impairment, patients with FD achieve a high level of social and emotional
      function. These data are important for prognosis and parental reassurance.

PMID- 15963776
TI  - Cross-sectional geometry of the human forefoot.
AB  - The human forefoot presents an interesting biomechanical problem of clinical
      importance because loads are distributed unequally across multiple bones. The
      fact that long bones typically have a several-fold safety factor relative to peak
      loads suggests that metatarsal strengths should be related to their peak loads.
      This study is the first to systematically examine the cross-sectional geometric
      properties of the human forefoot and their relationship to external loads during
      walking and running. We report midlength cross-sectional geometric properties
      (CA, Ix, Iy, Imax, Imin, J, Zx, and Zy) of metatarsals (1-5) and the hallucial
      proximal phalanx of a shod industrial population (n = 40) obtained using computed
      tomography. We then examine the relationship between these measures of shaft
      strength and published plantar pressure data sets recorded during the following
      functional activities: standing, at the push-off stage of the walking cycle, the
      full walking cycle, and running. Cross-sectional geometric properties of the
      first ray are greater than those of other rays, even when scaled to bone length.
      This pattern corresponds to the high pressures recorded for the first ray during
      most activities. The relationships between cross-sectional geometric properties
      of the lateral metatarsals and peak plantar pressure data are more complex.
      Metatarsals 2-4 are weakest in most cross-sectional geometric properties.
      However, metatarsal 2, and to a lesser extent metatarsal 3, experience relatively
      high peak pressures. On average, geometric measures of axial and bending
      strengths (adjusted relative to body size) are lower in females than males, and
      in European Americans than in African Americans, which corresponds to the
      respective rates of general metatarsal stress fracture in these groups. The
      discrepancy between strength and plantar pressure values in metatarsals 2 and 3
      is consistent with the high incidence of stress fractures in these bones and
      underscores the importance of soft tissues, such as the plantar fascia and flexor
      musculature, in moderating metatarsal shaft strain.

PMID- 15963777
TI  - Immunosuppression with FK506 has no influence on fracture healing in the rat.
AB  - Immunosuppressant drugs like cyclosporine A and FK506 are widely used for solid
      organ transplantation. They are accelerating bone remodeling but cause net bone
      loss. The aim of this study was to investigate the effect of FK506 on fracture
      healing in the rat. Eighty Lewis rats were divided into four groups, which
      received FK506 (1 mg/kg BW) or no treatment for 2 or 4 weeks, beginning after
      production of a closed, nondisplaced unilateral tibial fracture. Radiographic,
      histological, and biomechanical studies were used to evaluate fracture healing
      and histomorphometric analysis of the tibial metaphysis of the intact
      contralateral side was performed. Radiographs revealed no difference of the
      healing of the control fractures compared with the fractures in the FK506-treated
      group at 2 and 4 weeks. The mechanical parameters of the tested contralateral
      intact tibiae and of the fracture callus demonstrated no difference between
      control and immunosuppressed animals. Tibial bone histomorphometry revealed
      increased measures of bone formation and bone resorption, accompanied by a
      significant reduction of percent trabecular area. At 4 weeks, the fractures
      showed osseous healing with woven bone at the fracture site and only minimal
      amounts of cartilage. Histological grading was not different between the control
      and the FK506 group at both time points. We conclude that systemic application of
      FK506 has no biomechanical and histological effects of experimental fracture
      healing in the rat. However, resorption far in excess of formation leads to a net
      bone loss in the trabecular bone of the tibia that has no effect on the stability
      of the intact bone.

PMID- 15963778
TI  - PDZ domains and the politics of polarity in lymphocytes.
AB  - In this issue of Immunity, Ludford-Menting at al. (2005) show that scaffold
      proteins previously implicated in the control of epithelial cell polarity also
      play an important role in determining the macroscopic organization of the engaged
      T cell.

PMID- 15963779
TI  - Germinal centers still hold secrets.
AB  - There has been recent progress in understanding the mechanism of somatic
      hypermutation in germinal centers. By contrast, there is more theory than
      certainty about the way those cells that acquire heightened affinity for antigen
      are subsequently selected. Wang and Carter (2005) highlight this in the current
      issue of Immunity in a study of germinal center development in mice with impaired
      CD19 signaling.

PMID- 15963780
TI  - Infection, autoimmunity, and glycolipids: T cells detect microbes through self
      recognition.
AB  - De Libero et al. (2005) demonstrate in this issue of Immunity that bacterial
      infection leads to increased synthesis of autologous glycolipids that are
      recognized by CD1-restricted human T cells, indicating that recognition of
      inducible self-glycolipids could be a mechanism for microbial detection. This
      mechanism also may provide a connection between infection and autoimmunity.

PMID- 15963781
TI  - NOD2 and Crohn's disease: loss or gain of function?
AB  - The human nucleotide binding and oligomerization domain (NOD)-containing protein
      family consists of some 25 members related to the Apaf-1/Ced-4 family of
      apoptosis regulators and certain plant disease-resistance genes (Inohara et al.,
      2004). One member, NOD2 (CARD15), has gained recent prominence through its
      association with increased susceptibility to several clinically important human
      inflammatory diseases, especially Crohn's disease (CD). NOD2 is a cytoplasmic
      molecule involved in sensing microbial cell wall components and regulating
      inflammatory processes and apoptosis. This review focuses on recent insights into
      the functions of normal and variant NOD2 proteins and the pathogenetic mechanisms
      underlying NOD2-associated inflammatory diseases.

PMID- 15963782
TI  - A stress-induced, superoxide-mediated caspase-1 activation pathway causes plasma
      IL-18 upregulation.
AB  - Psychological/physical stresses are known to cause relapses of autoimmune and
      inflammatory diseases. To reveal a mechanism by which noninflammatory stresses
      affect host defenses, responses to immobilization stress in mice were
      investigated, focusing on the role of a multifunctional cytokine, interleukin-18
      (IL-18). In the adrenal cortex, the stress induced IL-18 precursor proteins (pro
      IL-18) via adrenocorticotropic hormone (ACTH) and a superoxide-mediated caspase-1
      activation pathway, resulting in conversion of pro-IL-18 to the mature form,
      which was released into plasma. Inhibitors of caspase-1, reactive oxygen species,
      and P38 mitogen-activated protein kinase (MAPK) suppressed stress-induced
      accumulation of plasma IL-18. These inhibitors also blocked stress-induced IL-6
      expression. This, together with the observation that IL-6 was not induced in IL
      18-deficient mice, showed that IL-6 induction by stress is dependent on IL-18. In
      stressed organisms, IL-18 may influence pathological and physiological processes.
      Controlling the caspase-1 activating pathway to suppress IL-18 levels may provide
      preventative means against stress-related disruption of host defenses.

PMID- 15963783
TI  - Serine protease cathepsin G regulates adhesion-dependent neutrophil effector
      functions by modulating integrin clustering.
AB  - The polymorphonuclear leukocyte (PMN)-derived serine proteases play a key role in
      immune complex (IC)-mediated inflammation. However, the mechanisms by which these
      proteases regulate inflammatory response remain largely undefined. Here, we show
      that IC-activated cathepsin G- and neutrophil elastase-deficient (CG/NE) PMNs
      adhered normally to IC-coated surfaces but did not undergo CD11b clustering and
      failed to initiate cytoskeletal reorganization and cell spreading. As a result,
      CG/NE-deficient PMNs exhibited severe defects in MIP-2 secretion and reactive
      oxygen intermediates production. Exogenously added CG, but not proteolytically
      inactive CG, was sufficient to restore these defects. These findings identify an
      important role for CG in integrin-dependent PMN effector functions that are
      separate from and downstream of integrin-dependent adhesion.

PMID- 15963784
TI  - PU.1 expression delineates heterogeneity in primary Th2 cells.
AB  - Primary T helper 2 cells are heterogeneous, expressing subsets of cytokines at
      varying levels. Mechanisms controlling this spectrum of phenotypes are still
      unclear. The ETS family transcription factor PU.1 is expressed in Th2 but not Th1
      cells. Th2 cytokine production is decreased in cultures transduced with a PU.1
      expressing retrovirus and increased in Th2 cells following RNAi that decreases
      PU.1 expression. In primary cultures, PU.1 expression is restricted to a
      subpopulation of Th2 cells that express CCL22 and a subset of Th2 cytokines. PU.1
      regulates the Th2 phenotype by interfering with GATA-3 DNA binding without
      altering GATA-3 protein levels. Thus, the expression of PU.1 in subsets of Th2
      cells establishes a defined cytokine profile and contributes towards establishing
      the spectrum of cytokine production observed in Th2 populations.

PMID- 15963785
TI  - Genetic evidence supporting selection of the Valpha14i NKT cell lineage from
      double-positive thymocyte precursors.
AB  - Invariant Valpha14i NKT (iNKT) cells are a specialized subset of T lymphocytes
      with regulatory functions. They coexpress TCRalphabeta and natural killer cell
      markers. They differentiate through interaction of their Valpha14-Jalpha18
      invariant TCRalpha chains with CD1d expressed on double-positive (DP) thymocytes.
      Although their development has been shown to be thymus dependent, their
      developmental pathway has not been definitively established. By using genetic
      analyses, we show here that all iNKT cells are selected from a pool of DP
      thymocytes. Their development is absolutely dependent on Runx1 and ROR(gamma)t,
      transcription factors that influence, but are not required for, development of
      conventional T cells. Our results indicate that even though CD1d binding DP
      thymocytes have yet to be observed, Valpha14-Jalpha18 rearrangement in these
      cells is required for development of iNKT cells.

PMID- 15963786
TI  - The transcriptional repressor Gfi1 controls STAT3-dependent dendritic cell
      development and function.
AB  - The mechanisms controlling the differentiation of dendritic cells (DCs) remain
      largely unknown. Using a transcriptional profiling approach, we identified Gfi1
      as a novel critical transcription factor in DC differentiation. Gfi1-/- mice
      showed a global reduction of myeloid and lymphoid DCs in all lymphoid organs
      whereas epidermal Langerhans cells were enhanced in number. In vivo, Gfi1-/- DCs
      showed striking phenotypic and functional alterations such as defective
      maturation and increased cytokine production. In vitro, Gfi1-/- hematopoietic
      progenitor cells were unable to develop into DCs. Instead, they differentiated
      into macrophages, suggesting that Gfi1 is a critical modulator of DC versus
      macrophage development. Analysis of hematopoietic chimeras and retrovirus
      reconstituted hematopoietic progenitor cells established a cell autonomous and
      nonredundant role for Gfi1 in DC development. The developmental defect of Gfi1-/-
      progenitor cells was associated with decreased STAT3 activation. In conclusion,
      we have identified Gfi1 as a critical transcription factor that controls DC
      versus macrophage development and dissociates DC maturation and activation.

PMID- 15963787
TI  - SLIM is a nuclear ubiquitin E3 ligase that negatively regulates STAT signaling.
AB  - STAT proteins are a family of latent cytoplasmic transcription factors that are
      activated by tyrosine phosphorylation in response to a variety of cytokines,
      growth factors, and hormones. Once activated, STAT proteins translocate into the
      nucleus and help coordinate gene transcription. One striking feature of STAT
      signaling is its rapid and transient activation and deactivation cycle, although
      the molecular mechanisms responsible for this remain poorly understood. Here, we
      report on a nuclear protein that contains both PDZ and LIM domains and that
      interacts with activated STAT4 molecules. We show that SLIM is an ubiquitin E3
      ligase that acts on STAT proteins to cause their proteosome-mediated degradation
      and enhance their dephosphorylation. Overexpression of SLIM leads to impaired
      STAT1 and STAT4 activity due to reduced STAT protein levels, while SLIM
      deficiency results in increased STAT expression and thus enhanced IFNgamma
      production by Th1 cells. These studies suggest that SLIM is a novel ubiquitin E3
      ligase whose targets include STAT proteins.

PMID- 15963788
TI  - A network of PDZ-containing proteins regulates T cell polarity and morphology
      during migration and immunological synapse formation.
AB  - T cell shape is dictated by the selective recruitment of molecules to different
      regions of the cell (polarity) and is integral to every aspect of T cell
      function, from migration to cytotoxicity. This study describes a mechanism for
      the regulation of T cell polarity. We show that T cells contain a network of
      asymmetrically distributed proteins with the capacity to dictate the subcellular
      localization of both cell surface receptors and morphological determinants in T
      cells. Proteins from the Scribble, Crumbs3, and Par3 complexes, previously shown
      to regulate epithelial polarity, were polarized in T cells containing either
      uropods or immunological synapses. Reduction in Scribble expression prevented the
      polarization of cell surface receptors and prevented morphological changes
      associated with uropod formation, migration, and antigen presentation. By
      dynamically coordinating molecular distribution throughout the T cell, this
      network provides a mechanism by which T cell function and polarity are linked.

PMID- 15963789
TI  - CD19 regulates B cell maturation, proliferation, and positive selection in the
      FDC zone of murine splenic germinal centers.
AB  - Mice with mutations in CD19 Y482/Y513 form germinal centers (GC) but fail to
      produce high-affinity antibodies. In these mice, GC B cell differentiation,
      proliferation, and class switching occur but are defective. Altered CD19
      signaling results in retention of early GC B cells and reduced proliferation in
      the follicular dendritic cell (FDC) zone of GC, and causes failure to select for
      high-affinity mutations. In normal mice, the earliest detectable aggregates of GC
      B cells are in contact with FDC and IgM+ cells are only found in the FDC zone,
      further evidence that the FDC zone is the site of initial GC B cell
      proliferation, differentiation, and class switching. Proliferation in the non-FDC
      zone and somatic mutation are not dependent on CD19, indicating separate
      signaling requirements for the two GC compartments, but these CD19-independent GC
      functions are not sufficient to generate high-affinity antibodies and B cell
      memory.

PMID- 15963790
TI  - Bacterial infections promote T cell recognition of self-glycolipids.
AB  - Recognition of self is essential for repertoire selection, immune regulation, and
      autoimmunity and may be a consequence of infection. Self-induced recognition may
      represent the escape mechanism adopted by pathogens but may also incite
      autoimmune diseases. Here, we show that bacterial infection may promote
      activation of T cells reactive to self-glycosphingolipids (self-GSL). CD1+
      antigen-presenting cells (APCs) infected with bacteria (Escherichia coli,
      Bacillus subtilis, Staphylococcus aureus, or Mycobacterium bovis-Bacillus
      Calmette Guerin [BCG]) or treated with the bacterial components
      lipopolysaccharide, lipoteichoic acid, or Pam3CysSerLys4 (P3CSK4) lipopeptide
      acquire the capacity to stimulate self-GSL-specific T cells to cytokine release.
      Immediately after infection, APCs increase the endogenous GSL synthesis and
      stimulate GSL-specific T cells in a CD1- and T cell receptor (TCR)-dependent
      manner. This stimulation may contribute to inflammatory responses during
      bacterial infections and may predispose individuals to autoimmune diseases.

PMID- 15963791
TI  - Ferritin in atherosclerosis.
AB  - Iron, an essential element for many important cellular functions in all living
      organisms, can catalyze the formation of potentially toxic free radicals.
      Excessive iron is sequestered by ferritin in a nontoxic and readily available
      form in a cell. Ferritin is composed of 24 subunits of different proportions of
      two functionally distinct subunits: ferritin H and L. The former is involved in
      ferroxidase activity necessary for iron uptake and oxidation of ferrous iron,
      while the latter is involved in nucleation of the iron core. The expression of
      ferritin is under delicate control and is regulated at both the transcriptional
      and posttranscriptional levels by iron, cytokines and oxidative stress. Elevated
      ferritin levels are associated with an increased risk of atherosclerotic coronary
      artery disease (CAD), the leading cause of death and illness in developed
      countries. Serum ferritin levels are a good indicator of iron stores in the body.
      In fact, epidemiological studies have suggested that elevated serum ferritin
      levels are associated with an increased risk of CAD and myocardial infarction
      (MI), though inconsistent results were obtained in some other studies. Moreover,
      recent proteomics and molecular biology studies have shown that ferritin levels
      in arteries are increased in diseased tissues, which further supports the link of
      ferritin to CAD/MI. Future studies will determine whether increased ferritin
      levels can serve as a distinct biomarker for the incidence of CAD/MI and
      distinguish whether increased ferritin levels are a cause of CAD or a consequence
      of the disease process.

PMID- 15963792
TI  - Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age
      related macular degeneration patients.
AB  - BACKGROUND: Epidemiological studies have established that a low serum
      concentration of carotenoids was associated with risk of Age-Related Macular
      Degeneration (ARMD). The aim of this study was to determine carotenoid levels in
      serum and in different lipoprotein fractions in patients diagnosed for ARMD and
      in matched control group. METHOD: Thirty-four ARMD patients and 21 control
      subjects from Brest area (France) have been included to this study. Lipoproteins
      have been separated from serum by gradient density ultracentrifugation. We
      measured concentration of carotenoids and tocopherols in serum and in different
      lipoprotein fractions by HPLC. RESULTS: No difference was observed between ARMD
      patients and control subjects in total serum carotenoids. Individual carotenoid
      levels showed that only lycopene was decreased significantly in serum, LDL and
      HDL fractions in patients (P<0.05). Concentrations in serum and lipoparticle
      fractions of lutein and zeaxanthin, the major pigments present in macula were not
      modified between both groups. CONCLUSIONS: Lycopene, as liposoluble antioxidant
      nutrient, is the only carotenoid altered in ARMD patients. It cannot be excluded
      that this effect is related to different dietary habits, but we hypothesise that
      lower lycopene status could result also from specific antioxidant protection of
      lutein and zeaxanthin by lycopene.

PMID- 15963793
TI  - Evaluation of analytical methods and workflow performance of the Architect ci8200
      integrated serum/plasma analyzer system.
AB  - BACKGROUND: The Architect ci8200 is an integrated serum analyzer for photometric,
      electrochemical and immunological assays. Several assays of each category and the
      workflow performance of the system were compared with established laboratory
      procedures in two laboratories. METHODS: Measurements were compared with the
      ELECSYS 2010 (Roche Diagnostics) for CEA, PSA, FPSA, AFP, folate, vitamin B12,
      with the CENTAUR (Bayer) for TSH, T4, FT4, FSH and Estradiol, with the LIAISON
      (DiaSorin) for TSH, FT4 and FT3, with the Behring Nephelometer BN II (Dade
      Behring) for ferritin, and with the INTEGRA 800 (Roche Diagnostics), and the
      AU640 (Olympus) for clinical chemistry assays. Workflow studies were performed to
      compare times of analysis required for defined analytical workloads. RESULTS: The
      coefficients of variation (CVs) for within-run imprecision were between 3% and 6%
      for CEA, PSA, FPSA, AFP and ferritin, and between 3% and 11% for TSH, FT4, FT3,
      folate and vitamin B12. The CVs for day-to-day imprecision for immunoassays were
      between 3% and 10%, except for vitamin B12 (CVs 11-13%) and FT4 (CV 10% -13%).
      For clinical chemistry tests corresponding CVs for within-run imprecision were <
      1%, except for HDL, triglyceride, creatinine, ALT, LD and lipase (CVs<2%) and
      bicarbonate (CV 3%-6%) and magnesium (CV < 3%). The CVs for day-to-day
      imprecision for clinical chemistry tests were < 1%, except for sodium, CO(2),
      magnesium, phosphorus, glucose, uric acid, HDL, triglyceride, ALT, AST CK, lipase
      with CVs < 6% and for CO(2)<11%. Dilutional linearity testing of seven
      immunoassays and five clinical chemistry analytes resulted in recovery rates of
      90-110%. Correlation studies with 15 immunoassays and 25 clinical chemistry tests
      showed acceptable agreements with established methods. Work flow analyses
      demonstrated a net gain in time of analysis up to 109 min depending on the size
      of the sample batch analyzed with the Architect ci8200 as the main analyzer as
      compared to the currently installed routine laboratory equipment. Median turn
      around times were 7 and 30 min for chemistry assays and immunoassays,
      respectively, when ordered as STAT analyses, and 18 min when chemistry assays
      were ordered as routine determinations. CONCLUSIONS: Assays on the Architect
      ci8200 performed well, fulfilling quality control requirements as defined for
      instance by German quality control guidelines (RiliBAK). Method comparisons
      showed acceptable agreements with established assays. Workflow studies using the
      Architect ci8200 documented shorter times of analyses as compared with the
      conventionally established laboratory routine demonstrating the potential of
      integrated chemistry/immunoassay analyzers to provide faster and more efficient
      performance.

PMID- 15963794
TI  - Development of methods for the detection and quantification of 7alpha
      dehydroxylating clostridia, Desulfovibrio vulgaris, Methanobrevibacter smithii,
      and Lactobacillus plantarum in human feces.
AB  - BACKGROUND: Mounting evidence suggests a relationship between bacterial
      metabolism of certain dietary and endogenous factors and the development of
      colorectal cancer. Deoxycholic acid (DCA) is a well studied co-carcinogen and bio
      transformation product of 7alpha-dehydroxylating Clostridia. H2S is a cytotoxic
      metabolite produced primarily by sulfate-reducing bacteria (SRB). The production
      of methane indicates low levels of active SRB. Lactic acid bacteria (LAB) have
      received attention recently due to their putative anti-tumor properties. METHOD:
      Human stool was spiked with pure cultures of bacteria and diluted in several
      enriched media. Each dilution titer was analyzed for the presence of the organism
      by PCR and biochemical assays. Duplicate stool aliquots were stored under various
      conditions for a 1 month period at -20 degrees C to test viability and detection.
      RESULTS: Growth and enumeration of each spiked organism was confirmed by PCR and
      biochemical assays. The combination of bead beating and chemical lysis steps
      produced the greatest DNA yields. PCR assays detected as low as 75 fg target DNA.
      The ability to detect Methanobrevibacter smithii, and Desulfovibrio vulgaris by
      either PCR or biochemical assay declined significantly after storage at -20
      degrees C for 1 month. CONCLUSIONS: Accurate detection and quantification of each
      bacterium using the described methods resulted when stool was processed
      immediately after collection. Storage of some members of the gut flora results in
      decrease in or loss of viability.

PMID- 15963795
TI  - Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by
      paclitaxel.
AB  - BACKGROUND: Paclitaxel, an antineoplastic drug, inhibits cell growth and cell
      cycle progression and induces apoptosis in human leukemia HL-60 cells. Caspase-3
      plays a direct role in proteolytic cleavage of cellular proteins responsible for
      progression to apoptosis. METHODS: We examined the cell morphology and apoptosis
      in HL-60 cells after exposure to paclitaxel and measured caspase-3 activities
      with or without z-VAD-fmk (a broad-spectrum caspase inhibitor) pretreatment by
      flow cytometric analysis and Western blotting. RESULTS: Together, our results
      were (1) paclitaxel mainly induced G2/M cell cycle arrest in HL-60 cells
      (p<0.001); (2) time (p<0.001)- and dose-dependent (p<0.001) apoptosis of HL-60
      cells was induced by paclitaxel; (3) in HL-60 cells, z-VAD-fmk blocked paclitaxel
      induced apoptosis (12 h: p<0.001; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.001) and
      caspase-3 activation (12 h: p<0.05; 24 h: p<0.01; 48 h: p<0.01; 72 h: p<0.01).
      CONCLUSIONS: These results suggest that paclitaxel can induce G2/M cell cycle
      transition and apoptosis via caspase-3 activity in HL-60 cells.

PMID- 15963796
TI  - Sensitive non-isotopic assays for autoantibodies to IA-2 and to a combination of
      both IA-2 and GAD65.
AB  - BACKGROUND: A sensitive ELISA for measurement of IA-2 autoantibodies has been
      developed and assessed. Also, a combination ELISA for detection of both GAD65
      autoantibodies and IA-2 autoantibodies is described. METHODS: The IA-2
      autoantibody assay is based on the ability of IA-2 autoantibodies to form a
      bridge between IA-2 intracellular fragment coated onto ELISA plate wells and
      liquid-phase IA-2 labelled with biotin. The combination ELISA uses plates coated
      with both IA-2 and GAD65 and a mixture of IA-2-biotin and GAD65-biotin. Assay
      sensitivity was assessed using the WHO reference (NIBSC 97/550) for islet cell
      antibodies. IA-2 autoantibody measurements by ELISA were compared with
      measurements in immunoprecipitation assays (IPAs) based on 125I or 35S labelled
      IA-2. Combination ELISA results were compared with results obtained for
      individual autoantibodies. RESULTS: As little as 15 units/mL of NIBSC 97/550 was
      detectable in the IA-2 autoantibody ELISA compared to 125 units/mL by 125I-IA-2
      IPA. 110/216(51%) sera from patients with type 1 DM were positive in the IA-2
      autoantibody ELISA while 97/216 (45%) and 91/216 (42%) were positive in the 125I
      IA2 and 35S-IA-2 IPAs, respectively. The IA-2 autoantibody ELISA showed 100%
      specificity for type 1 DM. The combination ELISA was able to detect GAD65 and/or
      IA-2 autoantibodies in 183/216 (85%) diabetic sera and 183/216 (85%) were also
      found positive for autoantibodies to IA-2 and/or to GAD65 in the assays for
      individual antibodies. Autoantibody measurements in the individual autoantibody
      assays and in the combination ELISA showed good agreement by Pearson correlation
      (r=0.92, n=216, p<0.001) and by Bland and Altman analysis. CONCLUSIONS: Sensitive
      and specific ELISAs for measurement of autoantibodies to IA-2 and to a
      combination of IA-2 and GAD65 have been developed. These assays are suitable for
      screening large numbers of samples in diabetes prediction and prevention trials.

PMID- 15963797
TI  - A review of the occurrence, analyses, toxicity, and biodegradation of naphthenic
      acids.
AB  - Naphthenic acids occur naturally in crude oils and in oil sands bitumens. They
      are toxic components in refinery wastewaters and in oil sands extraction waters.
      In addition, there are many industrial uses for naphthenic acids, so there is a
      potential for their release to the environment from a variety of activities.
      Studies have shown that naphthenic acids are susceptible to biodegradation, which
      decreases their concentration and reduces toxicity. This is a complex group of
      carboxylic acids with the general formula CnH(2n+Z)O2, where n indicates the
      carbon number and Z specifies the hydrogen deficiency resulting from ring
      formation. Measuring the concentrations of naphthenic acids in environmental
      samples and determining the chemical composition of a naphthenic acids mixture
      are huge analytical challenges. However, new analytical methods are being applied
      to these problems and progress is being made to better understand this mixture of
      chemically similar compounds. This paper reviews a variety of analytical methods
      and their application to assessing biodegradation of naphthenic acids.

PMID- 15963798
TI  - Leaching and degradation of ethametsulfuron-methyl in soil.
AB  - Leaching and degradation of the herbicide ethametsulfuron-methyl[methyl 2-[(4
      ethoxy-6-methylamino-1,3,5-triazine-2-yl)carbamoylsulfamoyl]benzoate] in three
      soils were investigated under laboratory conditions. Ethametsulfuron-methyl was
      mobile on soils when tested using non-aged and aged soil columns; this mobility
      agreed reasonably well with Freundlich soil isotherm constants. It was found that
      ethametsulfuron-methyl was more mobile in alkaline sandy Vertisol soil and
      neutral loamy Alfisol soil than in acidic clayey Red soil. Degradation of
      ethametsulfuron-methyl in soils was pH-dependent; calculated half-life (t(1/2))
      values ranged from 13 to 67 days. Ethametsulfuron-methyl was more persistent in
      neutral or weakly basic than in acidic soil. Five soil metabolites were isolated
      and identified by LC/MS/MS analysis. The degradation pathways included the
      cleavage of the sulfonylurea bridge, N- and O-dealkylation, and triazine ring
      opening.

PMID- 15963799
TI  - Moss (Bryum radiculosum) as a bioindicator of trace metal deposition around an
      industrialised area in Sardinia (Italy).
AB  - The moss Bryum radiculosum (Brid.), a species typical of dry and coastal
      environments, was used as a bioindicator for the estimation of atmospheric trace
      metal deposition around the industrial site of Portoscuso (Sardinia, Italy),
      which includes a lead-zinc smelter, two power plants, and aluminium production
      factories. For Cd, Pb, Zn, and V the results showed very similar patterns with
      extremely high values in the immediate surroundings of the industrial area.
      Copper and Cr showed somewhat different patterns, but still pointing to local
      pollution sources. The levels of metals at distance of about 13 km from the
      industrial site were still higher than in background samples. In order to
      evaluate the suitability of B. radiculosum for monitoring studies, trace metal
      concentrations in moss were compared with bulk deposition measurements in the
      same area. Correlation was significant only for Pb, Cd, and Zn. For Cr, Cu, and V
      the results showed high variability, mainly to be ascribed to soil factors.

PMID- 15963800
TI  - Dissipation of oxytetracycline, chlortetracycline, tetracycline and doxycycline
      using HPLC-UV and LC/MS/MS under aquatic semi-field microcosm conditions.
AB  - A mixture of four tetracyclines; oxytetracycline (OTC), chlortetracycline (CTC),
      tetracycline (TC), and doxycycline (DC) was applied in fifteen 12000l outdoor
      microcosms at four treatment levels plus controls each with three replicates (n =
      3). The dissipation times of parent compounds were monitored and half-lives
      (DT50) of 1-4 days, depending on treatment level were recorded. This is in
      accordance with half-lives from previous findings in bench-top experiments.
      Parent compound DT50, were determined using HPLC-UV. Furthermore, the samples
      were analyzed for ten different tetracycline products using LC/MS/MS. Two
      products were found for chlortetracycline; 4-epi-anh-chlortetracyline and the iso
      chlortetracycline. Iso-forms were only found for CTC and only at the highest
      treatment (300 microg l(-1)). The half-lives, trajectories, and relative amounts
      of the products were analogous for all four tetracyclines. DT50 for products were
      less than 1.2 days. Formation of 4-epi-anh-tetracyclines, occurred at neutral to
      weak alkaline conditions.

PMID- 15963801
TI  - Kinetic analysis of photocatalytic oxidation of gas-phase formaldehyde over
      titanium dioxide.
AB  - Degradation of formaldehyde with different initial concentration over titanium
      dioxide was carried out in a photocatalytic reactor. Photocatalytic rates were
      well described by the simplified Langmuir-Hinshelwood model. The kinetic analysis
      shows that the apparent first-order reaction coefficient is lower and half-life
      of photocatalysis is longer for low concentration than for high concentration
      formaldehyde. A network formation model of the photocatalytic products was
      established. Experimental results and analysis demonstrate that carbon dioxide
      concentration and carbon monoxide concentration in gas phase vary exponentially
      with the illumination time and may be even higher than gas-phase formaldehyde
      concentration if there is much pre-adsorbed formaldehyde in adsorption
      equilibrium on catalysts before illumination. Carbon monoxide is found to be one
      of the by-products during formaldehyde photooxidation.

PMID- 15963802
TI  - Fungal biodegradation of naphthalene: microcosms studies.
AB  - The present work is aimed to ascertain naphthalene biodegradation capability of
      P. chrysosporium and T. harzianum in soil microcosms. Considering the high
      naphthalene volatility, a suitable soil microcosm was set-up and used. Several
      degradation tests were conducted with different C/N ratio media for the two fungi
      in order to enquire the best range of working conditions. The kinetic studies
      were conducted at a maximal naphthalene concentration of 600 mg kg(-1). During
      experimental time course naphthalene concentration, CO2 evolution as well as
      phytotoxicity tests were performed as monitoring parameters. The results shown in
      the current paper, put in evidence that T. harzianum, differently than in liquid
      culture, is not able to biodegrade naphthalene directly in soil microcosm, while
      P. chrysosporium in the same conditions biodegrades the PAH till about 600 mg kg(
      1). As concern the founded kinetics for P. chrysosporium, a saturation shape in
      presence of N-limited medium (high C/N ratio) was evaluated while a growing form
      more than linear in no-N limited medium (normal C/N ratio) was determined.

PMID- 15963803
TI  - Applicability of Fenton and H2O2/UV reactions in the treatment of tannery
      wastewaters.
AB  - In this paper we evaluated the H2O2/UV and the Fenton's oxidation processes for
      the treatment of tannery wastewater under different experimental conditions.
      Efficiencies were judged by the amounts of organic substances degraded or
      eliminated under these treatment techniques. Daphnia magna and Vibrio fischeri
      were used to monitor toxicity. Organic compounds contained in the untreated and
      treated tannery wastewater were determined and identified using substance
      specific techniques. Gas chromatography-mass spectrometry (GC-MS) in positive
      electron impact (EI(+)) mode was applied to determine volatile organics.
      Atmospheric pressure ionization (API) mass (MS) and tandem mass spectrometry (MS
      MS) coupled with flow injection analysis (FIA) or liquid chromatography (LC) were
      used to detect or identify polar organic pollutants. The experimental results
      indicated that both oxidation processes--H2O2/UV at pH 3 and Fenton at pH 3.5-
      are able to reduce TOC content by mineralisation of the organic compounds.

PMID- 15963804
TI  - Inclusion complexes of alpha- and gamma-cyclodextrins and the herbicide
      norflurazon: I. Preparation and characterisation. II. Enhanced solubilisation and
      removal from soils.
AB  - The interaction of norflurazon with alpha- and gamma-cyclodextrins (CDs) yielded
      the formation of inclusion complexes at a 1:1 stoichiometric ratio in solution
      and in the solid state. Apparent stability constants of 50.7+/-1.6 and 37+/-1.7
      M(-1) and an increase in herbicide solubility by up to five and fourfold for
      alpha- and gamma-CD, respectively, were determined from the phase solubility
      diagrams at 25 degrees C in water. Three processing methods (kneading, spray
      drying and vacuum evaporation) were used to prepare norflurazon-CD solid
      inclusion complexes, which were characterised by infrared spectroscopy,
      differential scanning calorimetry and scanning electron microscopy. A high
      increase in the norflurazon dissolution rate was obtained with all the solid
      complexes with gamma-CD, but when alpha-CD was used, only the solid system
      obtained after the vacuum evaporation process showed a higher dissolution rate.
      This finding is a first step in the development of new, environmentally sound
      formulations of norflurazon (NFL), due to the capacity for increasing its
      dissolution rate and hydrosolubility, and thus diminishing the use of organic
      solvents. On the other hand, the effect of alpha- and gamma-cyclodextrin on the
      solubility of norflurazon in solution was also considered as a way of modifying
      its behaviour in the soil environment. Desorption studies of NFL from soils in
      the presence of alpha- and gamma-cyclodextrin were carried out using a batch
      equilibration method. The results obtained showed that alpha- and gamma
      cyclodextrin greatly increased the removal of norflurazon previously adsorbed,
      proving the potential use of these CDs for in situ remediation of pesticide
      contaminated soils.

PMID- 15963805
TI  - Arbuscular mycorrhizae enhance metal lead uptake and growth of host plants under
      a sand culture experiment.
AB  - A sand culture experiment was conducted to investigate whether mycorrhizal
      colonization and mycorrhizal fungal vesicular numbers were influenced by metal
      lead, and whether mycorrhizae enhance host plants tolerance to metal lead. Metal
      lead was applied as Pb(NO3)2 in solution at three levels (0, 300 and 600 mg kg(
      1) sand). Five mycorrhizal host plant species, Kummerowia striata (Thunb.)
      Schindl, Ixeris denticulate L., Lolium perenne L., Trifolium repens L. and
      Echinochloa crusgalli var. mitis were used to examine Pb-mycorrhizal
      interactions. The arbuscular mycorrhizal inoculum consisted of mixed spores of
      mycorrhizal fungal species directly isolated from orchard soil. Compared to the
      untreated control, both Pb concentrations reduced mycorrhizal colonization by 3.8
      70.4%. Numbers of AM fungal vesicles increased by 13.2-51.5% in 300 mg Pb kg(-1)
      sand but decreased by 9.4-50.9% in 600 mg Pb kg(-1) sand. Mycorrhizae
      significantly enhanced Pb accumulation both in shoot by 10.2-85.5% and in root by
      9.3-118.4%. Mycorrhizae also enhanced shoot biomass and shoot P concentration
      under both Pb concentrations. Root/shoot ratios of Pb concentration were higher
      in highly mycorrhizal plant species (K.striata, I. denticulate, and E. crusgalli
      var. mitis) than that in poorly mycorrhizal ones (L. perenne and T. repens,).
      Mycorrhizal inoculation increased the root/shoot ratio of Pb concentration of
      highly mycorrhizal plant species by 7.6-57.2% but did not affect the poorly
      mycorrhizal ones. In the treatments with 300 Pb mg kg(-1) sand, plant species
      with higher vesicular numbers tended to show higher root/shoot ratios of the Pb
      concentration. We suggest that under an elevated Pb condition, mycorrhizae could
      promote plant growth by increasing P uptake and mitigate Pb toxicity by
      sequestrating more Pb in roots.

PMID- 15963806
TI  - Metal contamination and solid phase partitioning of metals in urban roadside
      sediments.
AB  - This study was undertaken to assess the anthropogenic impact on metal
      concentrations of urban roadside sediments (N = 633) in Seoul city, Korea and to
      estimate the potential mobility of selected metals (Zn, Cu, Pb, Cr, Ni, and Cd)
      using sequential extraction. Comparison of metal concentrations in roadside
      sediments with mean background values in sediments collected from first- or
      second-order streams in Korea shows that Zn, Cu and Pb are most affected by
      anthropogenic inputs. The 206Pb/207Pb ratios of roadside sediments (range =
      1.1419-1.1681; mean 1.1576 +/- 0.0068) suggest that Pb is mainly derived from
      industrial sources rather than from leaded gasoline. A five-step sequential
      extraction of roadside sediments showed that Zn, Cd and to a lesser degree Ni
      occur predominantly in the carbonate bound fraction, while Pb is highest in the
      reducible fraction, Cu in the organic fraction, and Cr in the residual fraction.
      It was found that the concentrations in the readily available exchangeable
      fraction were generally low for most metals examined, except for Ni whose
      exchangeable fraction was appreciable (average 15.2%). Considering the proportion
      of metals bound to the exchangeable and carbonate fractions, the comparative
      mobility of metals probably decreases in the order of Zn > Ni > Cd > Pb > Cu >
      Cr. As potential changes of redox state and pH may remobilize the metals bound to
      carbonates, reducible, and/or organic matter, and may release and flush them
      through drain networks into streams, careful monitoring of environmental
      conditions appears to be very important. With respect to ecotoxicity, it is
      apparent the Zn and Cu pollution is of particular concern in Seoul city.

PMID- 15963807
TI  - Analysis of polycyclic aromatic hydrocarbons in wastewater treatment plant
      effluents using hollow fibre liquid-phase microextraction.
AB  - A simple and efficient method for the enrichment of low molecular weight
      polycyclic aromatic hydrocarbons (PAHs) in effluents originating from wastewater
      treatment plants is presented here. The proposed protocol couples the recently
      introduced hollow fibre liquid-phase microextraction (LPME) method with gas
      chromatography-mass spectrometry. Method parameters were controlled and the
      optimised experimental conditions were: 5 ml aqueous samples, containing 2.5%
      NaCl w/v, stirred at 1000 rpm, extracted with toluene for 15 min. The developed
      protocol yielded a linear calibration curve in the concentration range from 0.5
      to 50 microg l(-1) for all target analytes (namely acenaphthene, phenanthrene,
      fluoranthene and pyrene) and limits of detection in the low microg l(-1) level
      (0.005-0.011 microg l(-1)). The repeatability and inter-day precision of the
      method varied between 2.7% and 11.3% and 7.9% and 14.4% respectively. The
      relative recoveries from different types of natural water samples revealed that
      matrix had a small effect on the hollow fibre LPME process. The developed method
      was then applied for the determination of PAHs contamination in effluent samples
      taken from two major municipal wastewater treatment plants. The results were
      compared with those obtained with solid-phase microextraction. The ability of
      both microextraction methods to concentrate organic analytes was demonstrated as
      both methods confirmed the presence of PAHs as well as of phthalates in the
      examined effluent samples.

PMID- 15963808
TI  - Bioaccumulation and elimination of avermectin B1a in the earthworms (Eisenia
      fetida).
AB  - The acute toxicity, bioaccumulation, and elimination of avermectin B1a (AVM B1a)
      in earthworm (Eisenia fetida) were investigated in different exposure systems.
      The LC50 of AVM B1a on earthworms were 24.1 mg/kg and 17.1 mg/kg, respectively,
      for 7 and 14 days in artificial soil. The LC50 tested by the filter paper for 2
      days was 4.63 microg/cm2. The earthworms were cultivated in artificial soil
      containing 0.6 mg/kg and 3.0 mg/kg AVM B1a, respectively for bioaccumulation
      experiments. The AVM B1a residues in earthworms were determined with HPLC
      fluorescence method. The results showed that AVM B1a was taken up from the
      concentrated artificial soil by the earthworms and the steady-state levels were
      reached after 9-18 days of exposure. On the 18th day, the final concentrations of
      AVM B1a in the earthworms treated with two different dosages were 107 ng/g and
      165 ng/g, respectively; there were not significantly accumulation. About 80.0%
      and 94.8% of the accumulated AVM B1a were eliminated respectively in two groups
      within 1 day after they were exposed to AVM B1a-free soil, but a trace amount of
      AVM B1a was found for a relative long time in earthworms.

PMID- 15963809
TI  - Prediction of pesticide volatilization with PELMO 3.31.
AB  - In the current EU risk assessment for pesticide registration, the European
      Community requires prediction of the concentration of each pesticide in air. A
      number of mathematical models are used to assess the fate of pesticides in
      groundwater, surface water and soil. PELMO 3.20 calculates the volatilization
      fluxes from bare soil and was improved in the new version PELMO 3.31 to include
      the effect of temperature and sorption in dry soil. The objective of this study
      was to evaluate the new version of PELMO 3.31 in predicting the pesticide
      volatilization under field conditions. Procymidone, malathion, and ethoprophos
      were the test compounds in two different seasons (autumn and winter). Comparing
      simulation results obtained with PELMO 3.31, after calibration, with the previous
      version PELMO 3.20 shows that the estimated volatilization results seems improved
      for malathion, similar or slightly overestimating in the warmer season for
      ethoprophos, and similar or slightly underestimating in the colder season for
      procymidone. The new release of PELMO allows a more accurate estimation of
      pesticides volatilization from soil as function of meteorological factors,
      especially for medium or low volatility pesticides. Some difficulties remain,
      such as the determination of the active air layer and the sorption increment with
      the soil drying.

PMID- 15963810
TI  - Impact of radical versus non-radical pathway in the Fenton chemistry on the iron
      redox cycle in clouds.
AB  - Modeling studies have shown that the Fenton reaction of iron(II) with H2O2 can
      contribute, in a significant amount, to OH radicals production in cloud droplets.
      However, the destruction mechanism of hydrogen peroxide by iron(II) is still
      uncertain. Two reaction pathways for the first step of Fenton chemistry have been
      advanced: a radical pathway which considers an OH radical production and a non
      radical pathway considering ferryl ion production. The aim of this work is to
      evaluate the impact of these two possible reaction pathways for Fenton chemistry
      on the iron redox cycle in cloud droplets. For this purpose, the numerical model
      of multiphase chemistry M2C2 has been applied to a rural chemical scenario
      representative of continental conditions. This study highlights that the iron
      redox cycling is driven by Fenton reaction whatever Fenton mechanism is
      considered. The ferryl ion chemistry becomes significant in the iron redox
      cycling when this species is considered as an active intermediate in Fenton
      chemistry and under night time conditions the iron redox chemistry is controlled
      by the ferryl ion reactivity. The partitioning of iron between its two main
      oxidation states (+II and +III) in cloud droplets, which is the indicator of the
      iron oxido-reduction potential, does not change significantly between the two
      cases. However, for the non-radical case, the ferryl ion concentration is up to
      four orders of magnitude higher than the OH concentration highlighting its
      potential role in oxidative capacity of cloud droplets.

PMID- 15963811
TI  - Influence of hydroxypropyl-beta-cyclodextrin (HPCD) on the bioavailability and
      biodegradation of pyrene.
AB  - It is well known that the limited aqueous solubilities of polycyclic aromatic
      hydrocarbons (PAH) often reduce their bioavailability to bacterial populations.
      The objective of this study was to test the impact of a solubility-enhancement
      reagent, hydroxypropyl-beta-cyclodextrin (HPCD), on the bioavailability and
      biodegradation of pyrene. No measurable loss of pyrene occurred for the control
      vials throughout the first 22 weeks of the experiment, indicating the absence of
      mass loss via abiotic transformation and volatilization. The vials containing
      pyrene and the degrader isolate (Burkholderia CRE 7), but no HPCD, also exhibited
      no measurable loss of pyrene throughout the experiment. Conversely,
      biodegradation of pyrene appears to have been initiated after approximately 15
      weeks for the vials containing 10(4) mg l(-1) HPCD. By the end of the experiment,
      approximately 14% (w/w) of the pyrene was biodegraded in the presence of HPCD.
      These results indicate that HPCD may be useful for enhancing the bioavailability
      and biodegradation of pyrene and other PAHs.

PMID- 15963812
TI  - Twin pregnancy consisting of a complete hydatidiform mole and co-existent fetus:
      report of two cases and review of literature.
AB  - Hydatidiform mole with co-existing live fetus is a rare entity. Two cases are
      reported. In the first, complete mole with a co-existing live fetus was suspected
      on ultrasound examination at 16 weeks of gestation. A termination of pregnancy
      was performed due to early onset of severe preeclampsia and thyrotoxicosis. In
      the second case, the patient was admitted at 26 weeks of gestation due to
      preeclampsia. Genetic amniocentesis at 19 weeks of gestation revealed a normal 46
      XX karyotype. Ultrasound examination at 21 weeks of gestation demonstrated two
      cystic lesions in the fetal liver, wide multicystic placenta and polyhydramnious.
      Following deteriorating severe preeclampsia, a live female infant (730 g) along
      with a huge placenta (1350 g) was delivered by a cesarean section. Unfortunately,
      the newborn died after 35 days. Pathological examination in both cases was
      consistent with a complete mole co-existing with a viable fetus. During a 1 year
      follow up period, there was no evidence of persistent or metastatic disease in
      both cases. Review of literature discussing the diagnostic tools, clinical
      features, management and outcome of pregnancies with complete mole with a co
      existing live fetus is presented.

PMID- 15963813
TI  - An evaluation of cytotoxicity of the taxane and platinum agents combination
      treatment in a panel of human ovarian carcinoma cell lines.
AB  - OBJECTIVES: The objectives of this study were to determine the optimum schedule
      for combination of taxane and platinum agents in human ovarian carcinoma cell
      lines. METHODS: Cell growth inhibition was determined by the standard MTT assay
      and an IC(50) was calculated for docetaxel, paclitaxel, cisplatin, and
      carboplatin in seven human ovarian cancer cell lines (CAOV-3, OVCAR-3, SKOV-3, ES
      2, OV-90, TOV-112D, and TOV-21G). The IC(50) was defined as the drug
      concentration required for a 50% reduction in optical density. Cytotoxicity
      assays were performed with four sequential combinations of a taxane and a
      platinum compound. In each combination, cell lines were treated with the
      appropriate IC(50) of the drugs for varying time increments between 3 and 24 h.
      Controls were no drug, each agent alone and the combination of both. Results were
      obtained via manual cell counting with a hemocytometer. RESULTS: The inhibitory
      concentration to achieve 50% cell death (IC(50)) was determined for each compound
      in each cell line. The IC(50) ranged from 0.8 to 1.7 nM, 0.7 to 1.8 nM for
      docetaxel and paclitaxel, respectively, and 17.4 to 25.7 microM, 15.1 to 25.7
      microM for cisplatin and carboplatin, respectively. CONCLUSION: In this study the
      combination of docetaxel plus cisplatin was considerably more active in vitro
      than any of the other taxane plus platinum agent combinations evaluated in the
      panel of human ovarian cancer cell lines. In vitro activity was similar to
      previously report clinical studies comparing taxane and platinum combination
      regimens. This suggests the combination of docetaxel with cisplatin will have
      enhanced clinical activity compared to the paclitaxel plus carboplatin regimen.

PMID- 15963814
TI  - Recurrent giant fibroepithelial stromal polyp of the vulva associated with
      congenital lymphedema.
AB  - BACKGROUND: The relatively site-specific mesenchymal lesions of the vulvovaginal
      region can exhibit superficially overlapping histological features and can be
      diagnostically challenging. Fibroepithelial stromal polyp is generally an easily
      recognizable entity, but certain cases cause differential diagnostic problems.
      CASE: We present a case of a 16-year-old girl with a 10-cm polypoid lesion
      localized to the left labium. The patient has therapy resistant congenital
      lymphedema localized to the left arm and leg. The labial lesion was resected and
      recurred after 12 months and 6 years following the initial treatment.
      Histologically, it exhibited characteristics of a fibroepithelial stromal polyp
      with scattered bizarre multinucleated giant cells and ectatic tortuous lymphatic
      spaces. CONCLUSION: This vulvar lesion represents a unique example of giant
      fibroepithelial stromal polyp developed in association with Nonne-Milroy-Meiges
      syndrome.

PMID- 15963815
TI  - Hormonal treatment with aromatase inhibitors for patients with endometrial
      stromal sarcoma.

PMID- 15963816
TI  - Characterization of feline T cell receptor gamma (TCRG) variable region genes for
      the molecular diagnosis of feline intestinal T cell lymphoma.
AB  - A diagnosis of intestinal lymphoma is currently made on the basis of clinical and
      morphologic criteria. This can prove problematic for many reasons that include
      inadequate sample size, the coexistence of lymphoma and inflammation, and the
      inability to assess architectural integrity of all tissue compartments in biopsy
      specimens obtained endoscopically. The detection of a clonal population of cells
      in a lymphoproliferative lesion represents an important criterion for the
      diagnosis of neoplasia, but this has not been assessed in feline intestinal
      lymphoma. T cell receptor gamma (TCRG) gene rearrangement analysis using
      polymerase chain reaction (PCR) is a methodology that can be used to detect
      clonality in T cell populations. The basis of this assay depends on the
      assessment of the junctional diversity that results from rearrangement of TCRG V
      (variable) and J (joining) gene segments. Feline TCRG transcripts from normal
      small intestine and spleen were obtained using a rapid amplification of cDNA ends
      (5'RACE) method. Limited diversity of TCRG V and J gene segments was observed.
      The high degree of sequence homology in the TCRG V and J gene segments was
      exploited to develop a PCR test for the assessment of TCRG V--J junctional
      diversity and hence clonality determination of T cell populations in cats.
      Molecular clonality determination was applied to feline intestinal
      lymphoplasmacytic inflammatory bowel disease (IBD) (9 cats), and transmural and
      mucosal T cell lymphoma (28 cats). Clonal rearrangement of the TCRG V--J junction
      was detected in 22 of 28 intestinal T cell lymphomas, and oligoclonality was
      detected in 3 intestinal T cell lymphomas. This contrasted with the detection of
      polyclonal rearrangement in normal intestinal tissues (3 cats) and in
      lymphoplasmacytic IBD (9 cats). It is proposed that assessment of TCRG V--J
      junctional diversity for the detection of clonality represents an important
      adjunctive tool for the diagnosis of T cell lymphoma in the cat.

PMID- 15963817
TI  - Lineage differentiation of canine lymphoma/leukemias and aberrant expression of
      CD molecules.
AB  - Multiparameter flow cytometry analysis and specific cluster differentiation (CD)
      molecules were used to determine the expression profiles of B- and T-cell
      antigens on lymph node preparations from 59 dogs with generalized or
      multisystemic lymphoma. Lymph node samples from 11 healthy dogs were labeled to
      validate the specificity of antibodies and to formulate guidelines for
      interpretation of the results obtained from lymphoma samples. In normal lymph
      nodes, T-lymphocytes expressing CD3, CD4, or CD8 beta represented 59+/-11%, 43+/
      8%, or 16+/-5% of the total cells, whereas B-lymphocytes expressing either CD21
      or surface IgM (IgM) represented 37+/-9% or 14+/-5%, respectively. Small
      lymphocytes could be distinguished from large lymphocytes by forward light
      scatter. Of the patient samples 29 different breeds were represented with Golden
      and Labrador retriever being the most common. The lymphoma samples segregated
      into three groups based on CD antigen expression. Thirty cases predominantly
      expressed one or more combinations of CD79a, IgM, and CD21 representing a B-cell
      lineage. Three B-cell cases also expressed the stem cell antigen, CD34. Sixteen
      cases expressed one or more combinations of CD3, CD4, and CD8 consistent with a T
      cell lineage and CD3+CD4+CD8--phenotype was the most common. Thirteen cases
      showed a mixed expression profile for T- and B-cell antigens and in three cases
      CD14 was highly expressed. Clinical response was poorest for T-cell lymphomas.
      Leukemic states occurred in all three phenotypes; but mixed cell cases had the
      greatest proportion. Dual immunofluorescence staining confirmed co-expression of
      T-cell (CD3) and B-cell antigens (CD79a or CD21) on neoplastic lymphocytes of six
      mixed cell cases. In one mixed cell case, dual immunostaining identified
      lymphocyte populations that stained mutually exclusive for CD79a and CD3. Six
      mixed cell lymphomas tested by PCR showed clonality for rearranged antigen
      receptor. Four cases that were CD79a+CD3+ had TCRgamma chain gene rearrangements,
      whereas two cases that were CD3+CD8+CD21+ had Ig heavy chain rearrangement. One
      case expressing multiple CD molecules (CD3+CD8+CD21+CD14+) was PCR negative for
      both Ig and TCRgamma gene rearrangement and could not be classified into a B- or
      T-cell lineage. We show for the first time co-expression of B- and T-cell markers
      on lymphoma cells that had specific T- or B-cell gene rearrangements. These
      findings suggest that aberrant CD molecule expression is not an uncommon finding
      in canine lymphomas and is a useful diagnostic marker for malignancy.

PMID- 15963818
TI  - The kinetics of cytokine production and CD25 expression by porcine lymphocyte
      subpopulations following exposure to classical swine fever virus (CSFV).
AB  - Surface expression of IL-2R-alpha (CD25) is widely used to identify activated
      lymphocyte populations, while interferon-gamma (IFN-gamma) levels have been shown
      to be a good indicator of cell-mediated immunity (CMI) in pigs. To investigate
      the relationship between these two parameters, we developed an intracellular
      cytokine-staining assay and studied the kinetics of cytokine (IFN-gamma and
      interleukin-10, IL-10) production relative to CD25 expression in porcine
      lymphocyte subpopulations, following immunization with a classical swine fever
      (CSF) vaccine. The number of activated memory T cells (CD4(+)CD8(+)CD25(+) cells)
      increased slightly in the peripheral blood mononuclear cell (PBMC) population
      soon after vaccination, then diminished within a few weeks. The number of
      activated cytotoxic T cells (CD4(-)CD8(+)CD25(+) cells) peaked approximately 2
      weeks after the memory population. Although the number of IFN-gamma producing
      cells detected in this experiment was relatively low, the CD4(+)CD8(+) T cells
      were major IFN-gamma producers in the PBMCs throughout the experiment. In another
      experiment, CSF-vaccinated pigs were challenged with a virulent classical swine
      fever virus (CSFV), and the kinetics of CD25 expression and cytokine productions
      were monitored. Following exposure to the virus, the number of IFN-gamma
      producing cells in the PBMCs increased markedly in both the vaccinated and
      unvaccinated groups. The CD4(-)CD8(+) cells were major IFN-gamma producing cells
      in vaccinated pigs, while both CD4(+)CD8(+) and CD4(-)CD8(+) populations
      contributed to the IFN-gamma production in the control group. Interestingly, the
      enhanced IFN-gamma production was not associated with the upregulation of CD25
      expression following the CSFV challenge. In addition, exposure to the virulent
      CSFV significantly increased interleukin-10 production by the CD4(-)CD8(+)
      populations in PBMCs of the unvaccinated pigs. Taken together, our results
      indicated that CD25 expression and IFN-gamma production were not tightly
      associated in porcine lymphocytes. In addition, the CD4(-)CD8(+) lymphocytes of
      the PBMCs played a major role in cytokine productions following the CSFV
      challenge.

PMID- 15963819
TI  - Evaluation of cell-mediated immune responses and bacterial clearance in 6-10
      months old water buffalo (Bubalus bubalis) experimentally vaccinated with four
      dosages of commercial Brucella abortus strain RB51 vaccine.
AB  - Thirty water buffalo, obtained from a brucellosis-free farm, were used to
      evaluate cell-mediated immune responses and bacterial clearance in response to
      vaccination with Brucella abortus strain RB51 (RB51) in a dose-response study.
      The animals were randomly divided into five treatment groups. Groups I--V
      received the recommended dose (RD) of RB51 vaccine once, RD twice 4 weeks apart,
      double RD once, double RD twice 4 weeks apart and saline once, respectively. Cell
      mediated immune response to RB51 was assessed by the histological examination of
      haematoxylin and eosin (H&E) stained sections of lymph nodes draining the sites
      of inoculation and by comparison of stimulation indices (SI) derived from gamma
      interferon (IFN-gamma) assay. A mixture of cytoplasmic proteins from B.
      melitensis B115 (brucellergene) was used as a specific antigenic stimulus to
      peripheral blood mononuclear cells (PBMC) and lymph node mononuclear cells (LNMC)
      up to 22 post-initial-inoculation week (PIW). Supernatants harvested at 18-24h
      after the in vitro antigenic stimulus were assayed for their IFN-gamma content by
      using a commercial sandwich enzyme-linked immunosorbent assay (ELISA) kit.
      Clearance of RB51 was assessed by the sequential immunohistochemical examination
      of sections of draining lymph nodes post-inoculation. There was no observable
      expansion of the deep cortex of lymph nodes on H&E sections indicating poor T
      cell stimulation. All group V (control) water buffalo PBMC ELISA values were
      negative (SI<2.2) at all PIW sampling intervals. Overall PBMC IFN-gamma assay
      detected vaccinates from treatment groups' I--IV 67% (4/6), 83% (5/6), 33% (2/6)
      and 67% (4/6), respectively. LNMC IFN-gamma assay was unimpressive and there was
      a negative correlation (--.08) between the results of PBMC and LNMC of IFN-gamma
      assay. Clearance of RB51 occurred between 4 and 6 PIW in treatment groups I and
      III and between 6 and 12 PIW in groups II and IV. RB51 was not detected in any of
      the control animals at sampling intervals post-inoculation.

PMID- 15963820
TI  - Molecular cloning of interleukin-12 receptor beta2 chain and its expression in
      dogs.
AB  - This study cloned canine interleukin-12 receptor beta2 (IL-12Rbeta2). Its
      nucleotide sequences were determined. Canine IL-12Rbeta2 showed 85.4% homology at
      the nucleotide level and 76.8% homology at the amino acid level with human IL
      12Rbeta2. Its structural motifs were well conserved. We also cloned cDNA with a
      91-bp deletion including the transmembrane region, which produced a frame shift
      and an early stop codon. Examination of the expression of deleted canine IL
      12Rbeta2 mRNA revealed that both deleted and intact mRNAs were expressed at a
      constant ratio in all the dogs. Results suggested that expression of the deleted
      mRNA was constitutive and produced by alternative splicing.

PMID- 15963821
TI  - Toll-like receptor expression in feline lymphoid tissues.
AB  - Toll-like receptors (TLRs) are germline-encoded pattern recognition receptors
      (PRRs) that activate the innate immune system. While it is clear that TLRs are
      important in the immune response against pathogens, they may also be exploited by
      some pathogens. Our objective is to determine whether feline immunodeficiency
      virus (FIV) infection affects TLR expression or function thereby resulting in
      innate immune dysfunction. To this end, we cloned partial sequences for feline
      TLRs 1--3, 5--8, and developed real-time PCR assays to quantify feline TLRs 1--9.
      TLR expression was quantified in normal cat lymphoid tissues, purified lymphocyte
      subsets, and FIV-infected cell lines. Different expression patterns of TLRs were
      found in spleen, mesenteric lymph node, retropharyngeal lymph node, thymus,
      intestinal intraepithelial lymphocytes, and lamina propria lymphocytes. B
      lymphocytes, CD4+ T cells, and CD8+ T cells all expressed TLRs 2--5, 7--9;
      however, the relative levels of expression varied among lymphocyte phenotypes.
      Infection of cell lines with FIV resulted in altered TLR expression levels that
      differed depending on cell type. These results demonstrate that tissue
      distribution of TLRs is associated with the immunological role of a particular
      tissue, that lymphocytes may also express these 'innate immune' receptors, and
      that FIV infection can alter TLR expression.

PMID- 15963822
TI  - Serum immunoglobulin G concentration in Southern elephant seal, Mirounga leonina
      (Linnaeus, 1758), from Elephant Island (Antarctica): sexual and adrenal steroid
      hormones effects.
AB  - Serum immunoglobulin G (IgG; indirect enzyme-linked immunosorbent assay), as well
      as sexual and adrenal steroid hormones' concentrations (radioimmunoassay) were
      determined in 63 (male and female) Southern elephant seals (Mirounga leonine) at
      different developmental stages (weaned pups, juveniles and adults). In females,
      IgG values (mean+/-S.D.) were higher (P<0.05) in adults (15.9+/-6.5mg ml(-1))
      than in juveniles (7.9+/-4.0mg ml(-1)), but similar to weaned pups (12.0+/-5.0mg
      ml(-1)). Estrogen concentration was higher (P<0.05) in adults than in the weaned
      pups. In females, a significant (P<0.05) correlation (R=0.4) between serum IgG
      level and progesterone concentration was observed. In males, testosterone
      concentration was higher (P<0.05) in adults than in the juveniles and weaned
      pups. Aldosterone and cortisol concentrations were higher (P<0.05) in weaned pups
      (1056.0+/-643.1pmol 1(-1) and 272.7+/-110.0 nmol 1(-1), respectively) than in the
      juveniles (638.6+/-579.7pmol1(-1) and 152.9+/-97.3nmol 1(-1), respectively) and
      adults (386.5+/-209.1pmol (-1) and 145.7+/-67.3nmol 1(-1), respectively). These
      findings indicate that weaned pups are subjected to a higher natural stressful
      condition in the field. Despite this, humoral immunity, measured through IgG
      concentration, is not impaired in weaned pups.

PMID- 15963823
TI  - Lymphocytes of dogs immunised with purified excreted-secreted antigens of
      Leishmania infantum co-incubated with Leishmania infected macrophages produce IFN
      gamma resulting in nitric oxide-mediated amastigote apoptosis.
AB  - The role of nitric oxide (NO) in the anti-leishmanial activity has been confirmed
      both in vitro and in vivo. Recently, we demonstrated that NO-mediated apoptosis
      like amastigote death pathway is an important and highly regulated mechanism used
      for the clearance of Leishmania within infected murine macrophages stimulated to
      produce NO endogenously. To further characterize these important effector
      mechanisms in dog, a natural host-reservoir of L. infantum/L. chagasi, we have
      developed an ex vivo infection model of canine macrophages. Exposure of L.
      infantum-infected macrophages to autologous peripheral lymphocytes derived from
      dogs immunised with purified excreted-secreted antigens of L. infantum
      promastigotes (LiESAp) formulated with muramyl dipeptide (MDP) as adjuvant
      resulted in a significant leishmanicidal effect due to interferon (IFN)-gamma
      dependent macrophage activation. Concomitant accumulation of NO(3)(-)/NO(2)(-) in
      supernatants of co-cultured cells and in situ staining of parasites with terminal
      deoxynucleotidyltransferase-mediated dUTP nick-end labelling (TUNEL) and YOPRO-1
      showed that NO-mediated apoptosis of intracellular L. infantum amastigotes is
      occurring in canine macrophages as previously observed in mouse models.
      Monitoring these parameters in dogs after immunisation and before experimental
      challenge can represent a useful and easy way to rapidly evaluate vaccine
      candidates against canine visceral leishmaniasis.

PMID- 15963824
TI  - Improved protection from velogenic Newcastle disease virus challenge following
      multiple immunizations with plasmid DNA encoding for F and HN genes.
AB  - Specific-pathogen free (SPF) chickens were inoculated with the plasmid constructs
      encoding the fusion (F) and haemagglutinin-neuraminidase (HN) glycoproteins of
      Newcastle disease virus (NDV), either individually or in combination and
      challenged with velogenic NDV. The antibody level against NDV was measured using
      commercial enzyme linked immunosorbent assay (ELISA). In the first immunization
      regimen, SPF chickens inoculated twice with NDV-F or NDV-HN constructs elicited
      antibody responses 1 week after the second injection. However, the levels of the
      antibody were low and did not confer significant protection from the lethal
      challenge. In addition, administration of the plasmid constructs with Freund's
      adjuvant did not improve the level of protection. In the second immunization
      regimen, chickens inoculated twice with the plasmid constructs emulsified with
      Freund's adjuvant induced significant antibody titers after the third injection.
      Three out of nine (33.3%) chickens vaccinated with pEGFP-HN, five of ten (50.0%)
      chickens vaccinated with pEGFP-F and nine of ten (90.0%) chickens vaccinated with
      combined pEGFP-F and pEGFP-HN were protected from the challenge. No significant
      differences in the levels of protection were observed when the chickens were
      vaccinated with linearized pEGFP-F. The results suggested that more than two
      injections with both F and HN encoding plasmid DNA were required to induce higher
      level of antibodies for protection against velogenic NDV in chickens.

PMID- 15963825
TI  - Local interleukin-2 and interleukin-12 therapy of bovine ocular squamous cell
      carcinomas.
AB  - Interleukin-2 and interleukin-12 have been used independently to successfully
      treat the induced and the spontaneous tumours in animals. This trial was done to
      determine if a combination of IL-2 and IL-12 in the treatment of spontaneous
      bovine ocular squamous cell carcinomas (BOSCC) would be more successful than IL-2
      or IL-12 therapy by themselves. For this trial, we selected 25 BOSCC tumours seen
      on Holstein Fresian cows in Beatrice, Zimbabwe. The cows were randomly assigned
      to a treatment group of 5 days of IL-2 (200,000 U/day), 5 days of IL-12 (0.5
      microg/day) or 5 days of IL-2 (200,000 U/day) and IL-12 (0.5 microg/day). At 20
      months after treatment, the IL-2 therapy group had 63% complete regressions; the
      combination group had 38% complete regressions, which were significantly higher
      than the IL-12 group, which had 0% complete regressions at 20 months, despite
      having 29% complete regressions at 6 months. These results show that IL-2 therapy
      by itself and in combination with IL-12 is more successful than IL-12 by itself.
      However, combination therapy does not improve the outcome in comparison to IL-2
      as a single therapy. It also proves that IL-2 is consistently successful in the
      therapy of BOSCC with over 60% complete regression, which corresponds to a number
      of other studies we have done on IL-2 therapy of BOSCC [Rutten, V.P.M.G., Klein,
      W.R., De Jong, W.A., Misdorp, W., Den Otter, W., Steerenberg, P.A., De Jong,
      W.H., Ruitenberg, E.J., 1989. Local interleukin-2 therapy in bovine ocular
      squamous cell carcinoma. A pilot study. Cancer Immunol. Immunother. 30, 165--169;
      Stewart, R.J.E., Hill, F.W.G., Masztalerz, A., Jacobs, J.J.L., Koten, J.W., Den
      Otter, W., 2003. Local low dose interleukin-2 therapy of bovine ocular squamous
      cell carcinomas in cattle in Zimbabwe, submitted for publication; Den Otter, W.,
      Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder, P.H.M.,
      Rutten, V.P.M.G., Ruitenberg, E.J., 1993. Low doses of interleukin-2 can cure
      large bovine ocular squamous cell carcinoma. Anticancer Res. 13, 2453-2455; Den
      Otter, W., Hill, F.W.G., Klein, W.R., Koten, J.W., Steerenberg, P.A., De Mulder,
      P.H., Rhode, C., Stewart, R., Faber, J.A., Ruitenberg, E.J., 1995. Therapy of
      bovine ocular squamous cell carcinoma with local doses of interleukin-2: 67%
      complete regressions after 20 months of follow-up. Cancer Immunol. Immunother.
      41, 10-14].

PMID- 15963826
TI  - Differential expression of chemokine receptors and CD95 in porcine CD4(+) T cell
      subsets.
AB  - Among other differences, naive and memory T cells show distinct migratory
      patterns and susceptibility to CD95-mediated cell death. We have recently
      characterised in the pig two subsets of CD4(+) T cells, based on the expression
      of the 2E3 marker, that display phenotypic and functional features of naive
      (CD4(+)2E3(+)) and effector/memory (CD4(+)2E3(-)) T cells. In this study, we have
      analysed the expression of several chemokine receptors, as well as the
      distribution of CD95 antigen (APO-1/Fas) in these CD4(+) T cell subsets.
      CD4(+)2E3(-) T cells express high levels of CXCR3 and CCR4 transcripts but not of
      CCR7. On the contrary, CCR7 is clearly detected in CD4(+)2E3(+) T cells, whereas
      CXCR3 and CCR4 are negative or present at trace levels. These subsets also differ
      in the expression of CD95 antigen, being CD95 positive cells significantly more
      abundant in the CD4(+)2E3(-) cell subset. These findings, although based on a
      small number of animals, fit well with those reported for naive and memory CD4(+)
      T cells in humans.

PMID- 15963827
TI  - Protective immunity induced by a recombinant pseudorabies virus expressing the
      GP5 of porcine reproductive and respiratory syndrome virus in piglets.
AB  - Pseudorabies virus (PRV) has been developed as a vaccine vector for expressing
      foreign immunogens. Porcine reproductive and respiratory syndrome (PRRS), caused
      by porcine reproductive and respiratory syndrome virus (PRRSV), continues to be a
      major problem to the pork industry worldwide. Many vaccine strategies have been
      developed to control the disease but most of them turn out to be unsuccessful.
      The objective of this research was to explore the feasibility of PRV-based vector
      vaccine in protection against PRRSV. A live attenuated vaccine-based PRV
      recombinant expressing the envelope protein GP5 of PRRSV was generated using
      recombinant DNA techniques. The Bartha-K61-derived recombinant virus, named rPRV
      GP5, was shown to express PRRSV GP5 efficiently. Sixteen healthy piglets were
      assigned to one of four groups (one to four, four pigs per group). Animals in
      Groups 1 and 2 were each inoculated intramuscularly and intranasally with 10(7.0)
      PFU of rPRV-GP5 and its parent Bartha-K61, respectively; Group 3 were vaccinated
      intramuscularly with one-dose of PRRS inactivated vaccine; Group 4 was served as
      non-vaccinated control. One month later, all animals were all challenged with
      10(6.5) TCID(50) of virulent PRRSV CH-1a. All animals in Groups 1 and 3 remained
      clinically healthy before and after challenge, with only a short period of fever
      (no more than 41 degrees C and 3 days), mild and gradually improving lung and
      kidney lesions, and short-term viremia (2 and 3 week, respectively) in spite of
      no detectable anti-PRRSV antibody before challenge. On the other hand, all
      animals in the other two groups showed evident clinical signs with higher
      temperatures (more than 41 degrees C) after challenge, and severe lung, kidney
      and spleen lesions and extended viremia (4 weeks). The results indicate that the
      rPRV-GP5 is safe for vaccinates and able to confer significant protection against
      clinical disease and reduce pathogenic lesions induced by PRRSV challenge in
      vaccinated pigs.

PMID- 15963828
TI  - CMAP27, a novel chicken cathelicidin-like antimicrobial protein.
AB  - Cathelicidins, antimicrobial peptides with broad spectrum activity, have been
      almost exclusively found in mammals. Here, we report the cloning of a novel avian
      cathelicidin, chicken myeloid antimicrobial peptide 27 (CMAP27) from chicken bone
      marrow cells. A combined expressed sequence tag (EST) and genomic based search
      revealed a cathelicidin-like gene located at the terminus of chromosome 2.
      Reverse transcriptase-polymerase chain reaction (RT-PCR) and 5'RACE techniques
      resulted in a 154 amino acid prepropeptide, homologous to chicken cathelicidin 1
      (51%) and most similar to alpha-helical myeloid antibacterial peptides (MAPs; 29
      33%). A putative elastase cleavage site (LVQRG/RF) suggests the production of a
      27 amino acid antimicrobial peptide, predicted to adopt an alpha-helical
      configuration followed by a hydrophobic tail. Comparative analyses between
      antimicrobial peptide domains showed marked similarity between CMAP27 and MAP
      members of the bovidae family, but not with the alpha-helical chicken
      cathelicidin 1. Strongest expression of CMAP27 mRNA was found in myeloid/lymphoid
      tissues, testis and uropygial gland. In accordance with the phylogenetic tree
      analysis, these findings support the theory of a common ancestral cathelicidin
      gene and suggest an important role for cathelicidins in chicken innate host
      defense.

PMID- 15963829
TI  - [Evaluation of the disabilities of hemiplegic patients].
AB  - OBJECTIVES: To identify and describe the most useful functional disability scales
      for assessing post-stroke hemiplegic patients and those used largely in clinical
      trials. METHODS: A literature review of Medline about the functional parameters
      for balance, gait and mobility, upper extremity functional abilities, and
      activities of daily living. The metrologic properties of the scales were
      specified as were their clinical use. RESULTS: Thirty-three scales were evaluated
      and classified into five categories: balance (6 scales), gait and mobility (4),
      upper limb function (11), global motricity scales (5) and independence in
      activities of daily living (7). DISCUSSION AND CONCLUSION: Many functional scales
      are useful for assessing post-stroke hemiplegic patients. To assess balance, the
      Postural Assessment Stroke Scale and Berg Balance Scale are the most interesting.
      The Functional Ambulation Classification and the Timed Up and Go Test are the
      most relevant to assess gait and mobility. The Action Research Arm Test is
      largely used to assess upper limb functional abilities. The Functional
      Independence Measure and the Barthel Index are largely used to assess
      independence in activities of daily living.

PMID- 15963830
TI  - [Evaluation and multiple sclerosis].
AB  - We conducted a review of existing assessment tools that can be useful to physical
      medicine and rehabilitation professionals involved in the management of patients
      with multiple sclerosis (MS). Most generic tools traditionally used in
      neurorehabilitation, such as gait tests, the functional independence measure, or
      the SF-36, can be applied to MS, but few have been tested on large patient
      samples. Disease-specific scales often seem more pertinent and sensitive to
      change, and their qualities and limitations are better known through clinical
      trials of disease-modifying therapies.

PMID- 15963831
TI  - [Symptom and quality of life assessment in urinary disorders].
AB  - OBJECTIVES: To identify all available symptom and quality of life questionnaires
      for men and women with urinary disorders and assess their psychometric
      properties. METHODS: We systematically reviewed the literature in Medline using
      the key words urinary disorders, urinary incontinence, bladder, score, quality of
      life, questionnaire, and psychometric validation. RESULTS: The first search using
      the terms urinary incontinence and quality of life resulted in 1018 Abstracts.
      Articles mentioning but not measuring quality of life were not investigated.
      Questionnaires were selected because their psychometric properties were tested
      and they assessed how much a person was bothered by urinary symptoms or quality
      of life specific to urinary disorders. The questionnaires were usually gender
      specific. Their psychometric value was far from uniform, and, for most,
      responsiveness was not reported. CONCLUSION: Few quality of life questionnaires
      are at an advanced stage of validation to be applied in clinical practice. They
      need to be shorter, responsive and validated in different populations to permit
      their easy use.

PMID- 15963832
TI  - Travel and thrombosis.
AB  - The available evidence suggests an association between long distance travel and
      the development of venous thromboembolism. The main problem for travellers and
      physicians is the interpretation of the evidence and its translation into
      appropriate advice on the risk and the prevention of thrombosis. Most available
      data relate to air travel. Thrombosis risk is greater following journeys of more
      than 8 h and those at greatest risk are travellers with a history of venous
      thromboembolism or risk factors. Based on the best evidence available the risk of
      symptomatic venous thromboembolism after flights of more than 12 h is 0.5%. It is
      likely that stasis plays a major role in the aetiology of travel related
      thrombosis. The evidence for hypobaric hypoxia induced coagulation activation
      requires confirmation. There is evidence that compression stockings and low
      molecular weight heparin prevent asymptomatic deep vein thrombosis (DVT) but
      clinical DVT has been observed in long distance flyers in spite of prophylaxis
      with aspirin and stockings.

PMID- 15963833
TI  - Risk-adapted therapy in essential thrombocythemia and polycythemia vera.
AB  - The clinical course of Polycythemia vera (PV) and Essential Thrombocythemia (ET)
      is marked by an high incidence of thrombotic complications, which represent the
      main cause of morbidity and mortality. Major predictors of vascular events are
      increasing age and previous thrombosis. Myelosuppressive drugs can reduce the
      rate of thrombosis, but there is concern that their use raises the risk of PV and
      ET transformation into acute leukemia. To tackle this dilemma, a risk-oriented
      management strategy is recommended. Low-risk patients with PV should be treated
      with phlebotomy and low-dose aspirin, whereas those with ET can be left
      untreated. Cytotoxic therapy is indicate in high-risk patients and the drug of
      choice is hydroxyurea because its leukemogenicity is low, if any. New therapeutic
      options, theoretically devoid of leukemic risk, such as alpha-interferon,
      anagrelide and imatinib should be reserved to selected patients and require
      further clinical experience.

PMID- 15963834
TI  - Infections associated with purine analogs and monoclonal antibodies.
AB  - Nucleoside analogs and monoclonal antibodies are commonly used to treat
      lymphoproliferative disorders and have become established as the treatment of
      choice in chronic lymphocytic leukemia, hairy cell leukemia, and follicular
      lymphomas, as well as a number of other malignant lymphoid neoplasms. When used
      in standard doses, these agents have a low incidence of extramedullary side
      effects resulting in their inclusion in a number of combination regimens. The
      most important complications associated with these drugs are myelosuppression,
      immunosuppression and infections. This is further accentuated when they are used
      in combination with other drugs such as alkylating agents. Several investigators
      have attempted to delineate the risk factors predicting the risk of infections
      associated with these agents. Furthermore, risk-based strategies to decrease the
      incidence of these infectious complications have been proposed.

PMID- 15963835
TI  - The molecular physiology and pathology of fibrin structure/function.
AB  - The formation of a fibrin clot is a pivotal event in atherothrombotic vascular
      disease and there is mounting evidence that the structure of clots is of
      importance in the development of disease. This review describes the crucial
      events in the formation and dissolution of a clot, with particular focus on
      genetic and environmental factors that have been identified as determinants of
      fibrin structure in vivo, and discusses the substantiation of the relationship
      between fibrin structure and disease in conjunction with a review of the current
      literature.

PMID- 15963837
TI  - Fish consumption and blood mercury: proven health benefits or probable neurotoxic
      risk?

PMID- 15963836
TI  - Impact of residual and therapeutic doses of ciprofloxacin in the human-flora
      associated mice model.
AB  - A study was conducted to evaluate the effects of therapeutic and residual doses
      of ciprofloxacin on the human intestinal flora implanted into germ-free mice.
      Ciprofloxacin was administered daily via drinking water at concentrations to
      provide doses of 0, 0.125, 1.25, and 12.5mg/kg b.w. Changes in the intestinal
      flora composition, alteration in bacterial enzyme activities, fecal short chain
      fatty acid concentration and bacterial cellular fatty acid profiles, overgrowth
      of resistant bacteria, and disruption of the colonization barrier were the
      endpoints evaluated in the feces of human-flora-associated (HFA) mice.
      Ciprofloxacin at all tested doses decreased significantly the aerobic populations
      and particularly the population of Enterobacteriaceae. Selection of resistant
      Bacteroides fragilis group was noticed in HFA mice receiving 12.5mg/kg b.w. In
      mice challenged with a Salmonella strain, exogenous Salmonella persisted in the
      feces of all treated mice indicating that the flora responsible for the
      colonization barrier effect was disturbed by the antibiotic treatment. None of
      the studied metabolic parameters of the flora were affected by ciprofloxacin at
      any dose level. Under the experimental conditions of the study, the no-observed
      effect level of ciprofloxacin was found to be less than 0.125 mg/kg b.w.

PMID- 15963838
TI  - [Role of cutaneous pinch grafts in the healing of patients with dystrophic
      epidermolysis bullosa wounds: report of four cases].
AB  - Epidermolysis bullosa (EB) is a heterogeneous group of genetically determined
      skin fragility disorders in which minor trauma leads to blister formation on the
      skin. One of the most severe forms is Hallopeau-Siemens recessive dystrophic EB
      which main cause of mortality is squamous cell carcinoma (SCC). Exeresis of SCC
      leads to a difficult problem about treating the surgical wound. Most of the time,
      achieving a split-thickness skin graft on these severely affected EB patients is
      either too difficult or gives poor quality results. In some cases, flaps could be
      performed but they represent a too aggressive solution. However cutaneous pinch
      grafting is really adapted to the healing of these wounds. We have reported 4
      cases of patients with recessive dystrophic EB complicated with SCC from 30 mm to
      270 mm. After surgical excision of these SCC, dressings have been applied until
      obtaining a good enough floor for achieving a skin graft. The four patients have
      been treated by cutaneous pinch grafting. Airway management and monitoring have
      required particular precautions for avoiding anaesthetic related morbidity. We
      have noticed no adverse effect. A complete healing of good quality has been
      obtained in all cases (3 to 16 months of follow-up). No recurrence of SCC has
      been noticed and donors sites have had got a good healing. Relating to the
      healing of wounds after exeresis of SCC in case of dystrophic EB, cutaneous pinch
      grafting represents the most reliable solution with a minimum of physical
      traumatism.

PMID- 15963839
TI  - [Mondor's disease: a complication after breast surgery].
AB  - Mondor's disease is a rare but not uncommon complication of breast surgery. This
      problem is commonly described as the thrombophlebitis of the superficial
      thoracoabdominal veins. Symptoms combine painful contracture occurring in the sub
      mammary region and/or in the axillary region, rising during arm abduction. The
      contracture located in the axillary region usually join the epitrochlea. Based on
      a serie of 8 patients, the fascial hypothesis is developed. All the patients were
      treated by LPG and myo-fascial techiques with a complete relief of pain in 10
      days.

PMID- 15963840
TI  - [Social adjustment in French adults from who had undergone standardised treatment
      of complete unilateral cleft lip and palate].
AB  - France has a population of about 60 million peoples and each ten years data about
      the standard of living are collected by the central bureau of statistics, we
      considered the collection of data on 5000 households in 1999 in our geographical
      area would afford a unique opportunity to compare the equivalent status of French
      adults with repaired cleft of the lip and palate (CLP). Aspects of social
      adjustment were investigated in a sample of 82 French adults 18-35 years old with
      repaired complete unilateral cleft of the lip and palate (CLP). All subjects
      received a standardized regimen of care from the Burgundy cleft palate team of
      Dijon. The investigation, based on response to a questionnaire, partly replicated
      a national survey of social and economic life in the population (Standard of
      living survey Burgundy, INSEE France 1999), so that adults with complete clefts
      could be compared with a large control sample of the same age. The control group
      was constituted by subjects between 18 and 35 years in the standard of living
      survey Burgundy 1999, INSEE France, they were taken from a regional probability
      sample of households. This report covers education, employment, and marriage. The
      significant difference between groups was assessed by: Student's t-test or
      analysis of variance for continuous variables and chi2 test for categorical
      variables. The results demonstrated that there are significant differences in
      educational attainment and employment between adults with cleft of the lip and
      palate and other people. Fewer with cleft of the lip and palate marry, and when
      they marry they do so later in life, scholarship history showed significant delay
      in the cleft of the lip and palate group, independence regarding housing was
      lower in the cleft of the lip and palate group. If cleft of the lip and palate
      adults functioned within normal limits with regard to employment. However, levels
      of income were substantively lower than control groups. It would appear that
      cleft subjects experience some limitation in their ability to secure vocational
      and economic rewards from society. As a conclusion we can say regarding our
      results that the cleft of the lip and palate group, even with the smallest degree
      of malformation (unilateral without associated malformation), showed a
      significant delay in the independence process.

PMID- 15963841
TI  - [Our experience of otoplasty based on the study of the cartilaginous frame,
      especially the tail of the helix (about 244 cases and 22 anatomical
      dissections)].
AB  - Twenty-two anatomical dissections revealed interesting characteristics of the
      tail of the helix: first, this cartilage shows a ninety degrees' rotation so that
      its distal extremity finishes sagittally, setting the lobule location. Secondly
      it revealed the presence of a medial root going upwards under the anthehelical
      fold. Deformity of this root can impede the natural curling of the cartilage.
      These observations emphasize that the tail of helix is the key to otoplasty. The
      first surgical step consists in resecting the hypertrophic part of the helix
      tail, allowing its retroposition on the concha. A single Ethibond 4-0 suture is
      required to fix it in good position. This should correct the lobule protrusion
      and also nicely initiate the anthehelical fold. However, this anthehelical fold
      and its superior crus are to be completed by cartilage anterior scoring, carried
      upward and downward from a separate incision located on the anterior skin, at the
      top of the future superior crus of anthelix. The last step is a correction of the
      abnormal conchomastoid angle by resection of the redundant soft tissue and
      muscles. A single non-resorbable suture is also necessary to fix the concha to
      the mastoid tissue. Results of 244 otoplasties reported here show that it is a
      safe procedure associated with a high satisfaction score and a very low
      complication rate.

PMID- 15963842
TI  - [Eyelid crease incision for lateral orbitotomy].
AB  - Lateral orbital approach by eyelid crease incision constitutes a good way to the
      lateral sectors of the orbit allowing a good exposure, an invisible scar and
      light postoperative course. It constitutes a good alternative to the supero
      lateral approach which certainly, offers a good view but the heaviness of the
      postoperative course gives to the lateral orbitotomy all its interest. By a
      review of the literature, we try to report the advantages and the indications of
      this approach.

PMID- 15963843
TI  - [Cleft of the lower lip, mandible and sternum. A case report and review of the
      literature].
AB  - The Authors report a case of cleft interesting the lower lip and mandible with a
      sternal cleft. This association is exceptional, it was described in three world
      cases to this day. At this occasion, a review of the literature is realized, in
      particular concerning the associated malformatives anomalies and the therapeutic
      behaviour. It seems to us indispensable to realize an early reconstruction,
      specially bone correction, and to collaborate with a multidisciplinary team to
      obtain a good result and a better social incorporation of the child.

PMID- 15963844
TI  - [Face necrotizing fasciitis following spinocellular epithelioma excision].
AB  - Necrotizing fasciitis is a bacterial dermo-hypodermitis with superficial
      aponevrosis necrosis due to Streptococcus pyogenes. Head and neck region are some
      rare localization of this infection especially after surgery. We report herein a
      case of a face necrotizing fasciitis following minor face surgery. A 86 year-old
      Caucasian male without any antecedents, nor treatment, has been operated for a
      fronthead spinocellular epithelioma under local anesthesia. Twelve hours later, a
      severe pain localized to the face occurred, with sleeplessness, followed up with
      a face orbitary oedema and fever. Twenty-four hours later, an intravenous
      antibiotherapy was therefore started and surgical treatment was performed as soon
      as the diagnosis of necrotizing fasciitis was considered. An important
      inflammatory oedema was noticed, associated to a large necrotic softening of the
      face, the eyelid and the neck sub-cutaneous tissues. Then, the patient has been
      transferred in intensive care unit because multi-organ failure clinical and
      biological signs occurred. Pre-operatory bacteriological samples culture
      identified Streptococcus pyogenes. Repeated surgical explorations and debridement
      (excision, cleaning, draining and bandages recovery) were performed daily as
      needed until all the necrotic tissue was all eradicated. The antibiotherapy was
      prescribed to totalised 15 days. Our report underlines the importance of an early
      recognition of the diagnosis of soft tissue infection, because early surgical
      treatment has a better prognosis and antibiotic treatment alone is inefficient
      for the recovery. Alert is delivered by the local signs quickly followed up by
      skin changes. Anti-inflammatory therapy must be avoid in case of any soft tissue
      infection sign: they may increase the lesions, hide alarm signs and delay
      surgical treatment.

PMID- 15963845
TI  - [Testicular choriocarcinoma presenting as cutaneous metastasis. A case report and
      review of the literature].
AB  - Choriocarcinoma are germinal tumors from testicular cells in men or foetal
      trophoblast in women. Cutaneous metastasis are very rare. The authors report a
      case of angioma-like tumor in a 22-year-old man which was a cutaneous metastasis
      of a testicular carcinoma. Diagnosis was of course histologic. Testicular
      echography showed an intra testicular tumor, pulmonary and abdominal CT-scan
      showed multiple metastases. Orchidectomy and retroperitoneal lymphadenectomy were
      performed before a general chemotherapy. Patient died 14 months after diagnosis.
      Only 11 cases of cutaneous metastasis of choriocarcinoma were found in the world
      literature (7 men and 4 women). All cases showed diagnosis trap for plastic
      surgeon.

PMID- 15963846
TI  - [A tailor-made flap for an extremely severe case of hidradenitis suppurativa in
      the genital area].
AB  - Hidradenitis suppurativa is a chronic, suppurative and scarring disease
      characterized by painful, inflamed lesions in the axillae, perineum, groin,
      scrotum and other parts of the body with apocrine-bearing skin including genital
      skin. Appropriate medical treatment alone appears to be insufficient for managing
      most patients with severe lesions. In the vast majority of cases, surgery
      consists in complete excision of the lesions with primary closure or healing by
      secondary intention. In severe cases, radical excision of all diseased apocrine
      bearing skin is mandatory and the resulting defects are generally repaired by
      mesh skin grafts. In the most severe cases it may be necessary to realize loco
      regional flaps. Generally we reconstruct the perineal region with bilateral
      fasciocutaneous thigh flaps. We report a case of hidradenitis suppurativa where
      the lesions were so extensive from penis to anus we had to imagine a tailor-made
      flap based on the abdominoplasty techniques.

PMID- 15963847
TI  - [Dercum's disease: a severe complication in a rare disease. A case report].
AB  - Dercum's disease or adiposis dolorasa is unusual and unknown. Four symptoms are
      typical. It is characterized by painful subcutaneous fatty tumors in
      postmenopausal woman. We present this disease through the study of an uncommon
      clinical case: a sceptic choc following the "steato-cutaneous-necrosis" of a
      fatty tumor. The disease remains rare. The etiology is to this day unknown and
      different hypothesis (endocrinous, metabolic, genetics) are put forward. Multiple
      complications can occur but severe septicemia is rare. The treatment can be
      medical (loss of weight, corticoids, intravenous lidocaine) or surgical (surgical
      excision or liposuction).

PMID- 15963848
TI  - Converging pathways in leukemogenesis and stem cell self-renewal.
AB  - Studies over the last 40 years have led to an understanding of the hierarchical
      organization of the hematopoietic system and the role of the pluripotential
      hematopoietic stem cell. Earlier recognition of the importance of bone marrow
      hematopoietic microenvironments has evolved into the recognition of specific
      niches that regulate stem cell pool size, proliferative status, mobilization, and
      differentiation. The discovery of the role of multiple hematopoietic growth
      factors and their receptors in the orchestration of stem cell self-renewal and
      differentiation has been followed by recognition of the importance of the Notch
      and Wnt pathways. The homeobox family of transcription factors serve as master
      regulators of development and are increasingly found to be critical regulators of
      hematopoiesis. In parallel with this understanding of normal hematopoiesis has
      come a recognition that stem cell dysregulation at various levels is involved in
      leukemogenesis. Furthermore, the progression from chronic leukemia or
      myelodysplasia to acute leukemia involves accumulation of at least two mutational
      events that lead to enhancement of stem cell proliferation, or acquisition of
      stem cell behavior by a progenitor cell, coupled with maturation inhibition.
      Translocations resulting in development of oncogenic fusion genes are found in
      AML and the transforming potential of two of these, AML1-ETO and NUP98-HOXA9,
      will be discussed. Secondary, constitutively activating mutations of the Flt3 and
      c-kit receptors and of K- and N-ras are found with high frequency in AML, and the
      transforming potential of mutated FLT3 and the role of STAT5A activation in human
      stem cell transformation will be reviewed.

PMID- 15963849
TI  - Hypothesis: cell plasticity, linking embryonal stem cells to adult stem cell
      reservoirs and metastatic cancer cells?
AB  - Embryonal stem (ES) cells are the earliest ontogenetically identifiable stem
      cells of the embryo proper for all subsequent mesenchymal stem cells and for
      highly specialized differentiated cells. This review characterizes, in a working
      hypothesis, the role of reversible EMT/MET (epithelialmesenchymal transition) as
      a manifestation of cell plasticity 1) in the development of ES cells to adult
      stem cells (hematopoietic stem cells) and 2) in metastasizing cancer cells.
      Animal studies support the concept that EMT/MET is a key manifestation of cell
      plasticity in the development of ES cells to adult stem cells, and in conversion
      of localized to metastasizing cancer cells. In fact, ES cells may persist to
      postnatal life, in cytologically verifiable form and/or within the frame of
      EMT/MET, as ultimate reservoir for adult stem cells. Furthermore, EMT could
      possibly serve as a conceptional link between physiologic and pathologic
      signaling pathways. Clonal confirmation in humans is necessary.

PMID- 15963850
TI  - Oncogenic Ras blocks transforming growth factor-beta-induced cell-cycle arrest by
      degradation of p27 through a MEK/Erk/SKP2-dependent pathway.
AB  - OBJECTIVE: To examine whether oncogenic Ras affects transforming growth factor
      (TGF)-beta-mediated cell-cycle arrest in hematopoietic cells and the downstream
      signal transduction pathway involved in the interference with TGF-beta-induced
      cell-cycle arrest. MATERIALS AND METHODS: Two leukemic cell lines bearing N
      Ras(L61) mutations; HL-60 and TF-1, and the M1 cell line with wt Ras were
      investigated for their response to TGF-beta. Signal transduction inhibitors,
      overexpression and RNA interference studies were performed to investigate the
      involvement of the various proteins. RESULTS: Although TGF-beta signal
      transduction was not affected, G0-G1 arrest was absent in HL-60 and TF-1 cells
      due to the absence of p27. Overexpression of p27 restored TGF-beta-induced cell
      cycle arrest, as well as interfering in Ras-mediated signaling. The farnesyl
      transferase inhibitor L744832 and the MEK inhibitor U0126 both restored p27
      levels and cell-cycle arrest in response to TGF-beta. The absence of p27 protein
      is due to elevated levels of the ubiquitin ligase SKP2, which complexes with and
      targets p27 for degradation. RNA interference for SKP2 and treatment of these
      cells with the proteasome inhibitor MG132 restored p27 levels, corresponding with
      decreasing SKP2 levels after interfering in N-Ras signal transduction. P27,
      phosphorylated at threonine 187, is nuclear localized in N-Ras-containing cells.
      Mutation of this residue to alanine rendered p27 insensitive to degradation.
      CONCLUSION: N-Ras(L61) transformed cells lack a G0-G1 arrest upon TGF-beta
      treatment due to absence of p27. p27 is degraded through a MapK-, and SKP2
      dependent pathway. Overexpression of p27 results in restoration of cell-cycle
      arrest upon TGF-beta treatment.

PMID- 15963851
TI  - Expression of adducin genes during erythropoiesis: a novel erythroid promoter for
      ADD2.
AB  - OBJECTIVE: The first objective of this study was to examine the differences in
      levels of adducin (ADD1, ADD2, ADD3) mRNA expression during human erythropoiesis.
      The second objective was to determine whether the rapid induction of ADD2
      expression could be attributed to a novel erythroid-specific promoter. METHODS:
      Expression of mRNA was quantified using real-time RT-PCR. Primary erythroid
      precursors were isolated from normal human bone marrow using fluorescence
      activated cell sorting. Two model systems were compared: CD34(+) hematopoietic
      stem cells induced to differentiate with erythropoietin and HEL cells induced to
      differentiate with hemin. 5'RACE analysis was performed using primary human
      erythroblasts as starting material. RESULTS: All three adducin genes showed
      different patterns of expression during erythropoietic differentiation of
      cultured CD34(+) stem cells. Levels of ADD3 mRNA were higher than levels of ADD2
      mRNA at early stages of erythropoiesis. Expression of ADD2 was induced to very
      high levels (100 times baseline) in erythropoietin-stimulated cultures. 5'RACE
      analysis identified a novel starting exon and putative erythroid promoter for
      ADD2. CONCLUSION: These results suggest that expression of each adducin gene is
      regulated in a gene-specific manner during erythropoiesis. The early expression
      of ADD3 suggests that it may have a role in erythroblasts but is replaced by ADD2
      in later stages of erythropoiesis. The very high levels of expression of ADD2
      suggest that its promoter may be useful for directing erythroid-specific gene
      expression.

PMID- 15963852
TI  - RNAi-mediated knockdown of P-glycoprotein using a transposon-based vector system
      durably restores imatinib sensitivity in imatinib-resistant CML cell lines.
AB  - OBJECTIVE: Resistance to therapeutic drugs is a frequent phenomenon in
      hematologic malignancies, causing treatment failure in patients with leukemias
      and lymphomas. Overexpression of the multidrug-resistance gene (MDR-1) and its
      translational product P-glycoprotein (PgP) represents one mechanism of fatal drug
      resistance. METHODS: We constructed a nonviral, transposon-based vector system
      for the stable knockdown of PgP in chronic myeloid leukemia cell lines resistant
      to imatinib and doxorubicin. RESULTS: Using this strategy, PgP expression was
      completely knocked down 72 hours after vector inoculation and lasted for several
      months. Cellular efflux of the PgP substates rhodamine and doxorubicin was
      abolished. Vector-treated cells were resensitized to imatinib- and doxorubicin
      induced cell death. CONCLUSION: Using chronic myeloid leukemia as a model, we
      show that PgP-mediated resistance to imatinib and anthracyclines can be durably
      reversed by nonviral, transposon-based knockdown of PgP in malignant cells.

PMID- 15963853
TI  - Mice severely deficient in growth hormone have normal hematopoiesis.
AB  - OBJECTIVE: Many studies suggest that growth hormone (GH) is important for
      hematopoietic stem cell (HSC) function. The objective of this study is to
      determine if the genetic absence of GH reduces hematopoietic function and
      recovery, by testing various points in hematopoiesis, from numbers and functional
      abilities of primitive stem cells to the maintenance of normal numbers of
      differentiated cells. MATERIALS AND METHODS: Analyses were conducted on blood and
      bone marrow to compare GH-deficient C57BL/6J-Ghrhr(lit) / Ghrhr(lit) (lit/lit)
      mice with their normal (lit/+) littermates. Flow cytometric analysis was used to
      measure numbers of HSC and progenitor cells based on antigenic markers. Spleen
      colony-forming units (CFU-S) were examined to determine function of common
      myeloid progenitor (CMP) cells. Competitive repopulation assays were conducted to
      test whether normally functional HSCs are produced and supported in the lit/lit
      hematopoietic environment. RESULTS: The lit/lit mutant mice produced HSC and
      progenitor cells at least as well as their lit/+ control littermates. In CFU-S
      assays, the CMP from the lit/lit mice functioned as well as those from the lit/+
      controls. Marrow cells from lit/lit mice repopulated irradiated recipients long
      term better than did marrow cells from C57BL/6J(+/+) controls; thus, HSC produced
      in the absence of GH can replenish irradiated recipients. When lit/lit mice were
      used as irradiated recipients, they supported HSC function as well as lit/+
      control recipients did; thus, the lit/lit hematopoietic environment can support
      normal hematopoiesis.

PMID- 15963854
TI  - PS-341-mediated selective targeting of multiple myeloma cells by synergistic
      increase in ionizing radiation-induced apoptosis.
AB  - OBJECTIVE: Multiple myeloma remains incurable with current therapy. The
      proteosome inhibitor, PS-341, has shown objective clinical responses in relapsed
      refractory myeloma patients. We investigated the potential of enhancing the
      radiosensitivity of myeloma cells by combining with PS-341; the underlying
      mechanisms were delineated. MATERIALS AND METHODS: Clonogenic assays were used to
      evaluate cell survival after exposure to PS-341, ionizing radiation (IR), or PS
      341 followed by IR. Apoptosis was studied by annexin V-propidium iodide staining
      and caspase activation. Cell-cycle phase distribution of cells was determined.
      Nuclear factor-kappaB (NF-kappaB) activity was monitored by enzyme-linked
      immunosorbent assay and Western blotting. The expression of death receptor
      Fas/APO-1/CD95 was analyzed by flow cytometry. The consequential caspase-8
      activation was detected by Western blotting. RESULTS: In clonogenic assays,
      sequential exposure to nontoxic doses of PS-341 (10 nM) and IR (6 Gy) resulted in
      synergistic inhibition of proliferation of myeloma cells by modulating the
      apoptotic sensitivity of these cells. Biochemically, sublethal dose of IR led to
      potent induction of NF-kappaB activity, and this response was significantly
      inhibited by pretreatment with PS-341, or by the NF-kappaB inhibitory peptide SN
      50. Enhanced Fas expression was seen in myeloma cells exposed sequentially to PS
      341 and IR. Finally, PS-341 sensitized primary myeloma (CD138+ve) cells to IR but
      had little effect on CD138-ve bone marrow cells from myeloma patients.
      CONCLUSION: These data indicate that PS-341 can sensitize myeloma cells to IR by
      both intrinsic and extrinsic apoptotic pathways. The study indicates improved
      therapeutic benefits in treatment of multiple myeloma by combining PS-341 with
      conventional radiotherapy.

PMID- 15963855
TI  - A paradoxical role for IFN-gamma in the immune properties of mesenchymal stem
      cells during viral challenge.
AB  - OBJECTIVE: The functional "plasticity" and immune-suppressive effects of human
      bone marrow (BM)-derived mesenchymal stem cells (MSC) provide them with the
      potential to be used across allogeneic barriers. The immunosuppressive properties
      of MSC may be detrimental in a clinical setting in which viral exposure is
      common. The study hypothesizes that MSC-derived IFN-gamma could offset the immune
      suppressive functions of MSC and mediate partial CTL responses during viral
      infection. METHODS: CTL responses were studied in bioassays with (51)Cr-P815
      targets and PBMC (uninfected or infected) as effectors. Immunofluorescence
      studied the relative expression of CD8(+) cells. Cytokine analyses were performed
      with microarrays. Roles for IFN-gamma in CTL responses were studied with
      IFNgammaRI mAb or with MSC knockdown for IFN-gamma by siRNA (pPMSKH1-IFNgamma).
      RESULTS: MSC showed no significant effect on circulating CTL of healthy subjects.
      For virus-induced CTL, MSC demonstrated approximately 50% suppression. CD8(+)
      cell expansion could not explain the suppressive effects of MSC. Soluble factors
      produced by MSC were responsible for the retention of 50% CTL responses. Cytokine
      microarray analyses, noncontact cultures, and functional assays identified a role
      for IFN-gamma. MSC were identified as the relevant source of IFN-gamma.
      CONCLUSION: The results show a facilitating role of IFN-gamma on CTL responses,
      although paradoxical in light of the veto properties of MSC. This report shows
      that in cases where MSC are used in transplantation for repair of damaged tissue,
      they can exert an additional role by protecting the host to viral challenges and
      thereby protect from its immunosuppressive properties.

PMID- 15963856
TI  - Antigen-recognition sites of micromanipulated T cells in patients with acquired
      aplastic anemia.
AB  - OBJECTIVE: Acquired aplastic anemia (AA) is a rare disorder characterized by
      pancytopenia and hypocellular bone marrow. Though experimental and clinical data
      suggest that AA represents a T cell-mediated disease, neither the immune response
      nor the nature of inciting antigen(s) have been characterized so far. The
      identification of a restricted T cell repertoire by PCR techniques in total
      lymphocyte populations supports an antigen-driven T cell response. In order to
      investigate the clonal composition, we analyzed the gene rearrangements of the T
      cell receptor (TCR) variable beta chain (Vbeta) at the single-cell level.
      PATIENTS AND METHODS: CD3(+) T lymphocytes were micromanipulated from peripheral
      blood and bone marrow samples of 8 AA patients and healthy controls. Subsequently
      amplified VDJ gene segments of the TCRVbeta chain were analyzed for functional
      rearrangements. More than 500 functionally rearranged TCR loci were studied for
      Vbeta/Jbeta gene segment usage and molecular composition of the complementary
      determining region 3 (CDR3). RESULTS: In comparison to healthy controls, the
      Vbeta sequences confirmed a highly restricted T cell repertoire in AA patients at
      the single-cell level. Both in bone marrow and peripheral blood a predominance of
      Vbeta13 and Jbeta2S7 was observed. Furthermore, individual clonal T-cell
      expansion was identified in the majority of patients. However, deduced CDR3 amino
      acid sequences revealed a high variability without common motifs among the 8
      patients. CONCLUSION: Individual clonal T-cell expansion with high diversity of
      the antigen-binding sites among the analyzed patients argues for the predominance
      of private inciting epitopes in AA.

PMID- 15963857
TI  - Differential regulation of perforin expression in human CD4+ and CD8+ cytotoxic T
      lymphocytes.
AB  - OBJECTIVE: Because perforin is an essential cytolytic mediator of cytotoxic T
      lymphocytes (CTLs), it is important to understand the regulatory mechanisms of
      perforin expression in CTLs. In the present study, we investigated the
      relationship between cytotoxic activity, perforin expression, and cell-activated
      status of CD4(+) and CD8(+) CTLs. METHODS: Herpes simplex virus-specific CD4(+)
      CTL clones and Epstein-Barr virus-specific CD8(+) CTL clones were established,
      and their cytotoxic activities were examined in both the activated and resting
      phases. Perforin mRNA expression was examined by reverse transcriptase polymerase
      chain reaction quantitatively. Transcriptional regulation of perforin was
      examined by electrophoretic mobility shift assay. RESULTS: The degrees of
      cytotoxic activity of CD8(+) CTLs did not differ significantly between the two
      phases; however, CD4(+) CTLs in the activated phase appeared to be significantly
      more cytotoxic than those in the resting phase. Similarly, expression levels of
      perforin mRNA in activated and resting CD8(+) CTLs did not differ significantly,
      but activated CD4(+) CTLs appeared to express perforin more abundantly than
      resting CD4(+) CTLs. In addition, it appeared that binding of STAT5 to the
      perforin gene promoter was increased in activated CD4(+) CTLs compared to resting
      CD4(+) CTLs; however, there was no significant detectable difference of STAT5
      binding activity to the perforin gene promoter between activated and resting
      CD8(+) CTLs. CONCLUSIONS: The present study has revealed a difference in the
      control of perforin expression between CD4(+) and CD8(+) CTLs; that is, perforin
      is expressed constitutively in memory CD8(+) CTLs, but is dependent on cell
      activation in memory CD4(+) CTLs.

PMID- 15963858
TI  - T-cell suppression mediated by mesenchymal stem cells is deficient in patients
      with severe aplastic anemia.
AB  - OBJECTIVE: To compare the suppressive effect of mesenchymal stem cells (MSC),
      derived from normal individuals or severe aplastic anemia patients (SAA), on T
      cell activation. PATIENTS AND METHODS: We studied bone marrow MSC from 19 healthy
      donors and 23 SAA patients in different phases of the disease: at diagnosis (n =
      3), following immunosuppressive therapy (IS) (n = 16), or after a bone marrow
      transplant (BMT) (n = 4). MSC were tested for T-cell suppression in the following
      assays: mixed lymphocyte reaction (MLR), phytohemaglutinin (PHA)-primed cultures,
      activation surface markers, gamma-IFN production, hematopoietic colony formation
      (CFC), production of cyclic ADP-ribose (cADPR). RESULTS: The abnormalities of SAA
      MSC included: 1) significantly lower suppression of T-cell proliferation induced
      by alloantigens (p = 0.009) or PHA (p = 0.006); 2) impaired capacity to suppress
      CD38 expression on PHA-primed T cells (p = 0.001); 3) impaired ability to
      suppress gamma-IFN production in PHA cultures, resulting in an 11-fold higher
      gamma-IFN concentration; 4) no preventive effect on T cell-mediated inhibition of
      CFC; and 5) significantly reduced (p = 0.009) production of cADPR, a universal
      calcium mobilizer. MSC-mediated suppression of PHA-induced T-cell proliferation
      was restored to control levels in 3 of 4 patients post-BMT. CONCLUSION: The
      ability of MSC to downregulate T-cell priming, proliferation, and cytokine
      release is deficient in patients with SAA, persists indefinitely after
      immunosuppressive therapy, but seems to be restored after BMT. Whether these
      abnormalities are relevant to the pathogenesis of aplastic anemia remains to be
      determined.

PMID- 15963859
TI  - A human stromal-based serum-free culture system supports the ex vivo
      expansion/maintenance of bone marrow and cord blood hematopoietic stem/progenitor
      cells.
AB  - OBJECTIVE: We investigated the role of human stromal layers (hu-ST) on the ex
      vivo expansion/maintenance of human hematopoietic stem/progenitor cells (HSC)
      from adult bone marrow (BM) and umbilical cord blood (CB). MATERIALS AND METHODS:
      BM and CB CD34(+)-enriched cells were cultured in serum-free medium supplemented
      with SCF, bFGF, LIF, and Flt-3, in the presence or absence of stroma, and
      analyzed for proliferation, phenotype, and clonogenic potential. RESULTS:
      Significant expansion of BM and CB CD34(+) and CD34(+)CD38(-) cells were achieved
      in the presence of hu-ST. The differentiative potential of both BM and CB CD34(+)
      enriched cells cocultured with hu-ST was primarily shifted toward the myeloid
      lineage, while maintaining/expanding a CD7(+) population. Clonogenic analysis of
      the expanded cells showed increases in progenitors of the myeloid lineage,
      including colony-forming unit-granulocyte, macrophage (CFU-GM) and colony-forming
      unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU-Mix) for both BM
      (stroma and stroma-free conditions) and CB cells in the presence of stroma.
      CONCLUSIONS: These results indicate that adult hu-ST in the presence of
      appropriate cytokines can be used to efficiently expand/maintain myeloid and
      lymphoid cell populations from human BM and CB HSC.

PMID- 15963860
TI  - Roles of Sca-1 in hematopoietic stem/progenitor cell function.
AB  - OBJECTIVE: This study was focused on studying the role of Sca-1 (Ly-6 A/E) in
      hematopoietic stem/progenitor cell self-renewal, activation, and lineage fate.
      MATERIALS AND METHODS: Sca-1(-/-) bone marrow cells were transplanted into wild
      type recipient mice and assessed for self-renewal activity and lineage choice. In
      addition, Sca-1(-/-) mice were injected with 5-FU and Lin(-) cells were analyzed.
      Sca-1 was also overexpressed in mouse and human stem/progenitor cells to assess
      the effect of Sca-1 overexpression on stem/progenitor differentiation and
      proliferation. RESULTS: Self-renewal of Sca-1(-/-) HSC appeared to be normal, but
      lineage skewing was observed in B cells, NK cells, and granulocytes/macrophages
      derived from Sca-1(-/-) HSC. There was also a decrease in c-kit expression on
      activated Sca-1(-/-) progenitor cells. Overexpression of mouse Sca-1 decreased
      the in vitro myeloid activity of both mouse and human progenitors. CONCLUSION:
      These data indicate that Sca-1 plays a role in hematopoietic progenitor/stem cell
      lineage fate and c-kit expression. In addition, mouse Sca-1 overexpression
      affects human as well as mouse stem/progenitor cell activity, suggesting the
      possibility of a functional human Sca-1 homologue.

PMID- 15963861
TI  - Improving end-of-life care: development and pilot-test of a clinical pathway.
AB  - Prior studies have revealed deficiencies in the care provided to patients dying
      from advanced medical illnesses in acute care hospitals. These deficiencies are
      best addressed through system change, which may include the development of
      clinical pathways and quality improvement models. The Palliative Care for
      Advanced Disease (PCAD) pathway was developed by an interdisciplinary team and
      includes a carepath, a daily flowsheet, and a physician order sheet with standard
      orders for symptom control. To evaluate the utility of PCAD, the clinical pathway
      was introduced on three hospital units (Oncology, Geriatrics, and an inpatient
      palliative care/hospice unit) as part of a quality improvement initiative and
      outcomes were compared to two general medical units receiving usual care. A chart
      audit tool (CAT) was used to review medical records of 101 patients who died on
      one of these five units during the year prior to implementation (baseline) and
      156 who died during the nine months of the PCAD intervention. Four indices from
      CAT evaluated change over time: the mean number of 1) symptoms assessed, 2)
      problematic symptoms, 3) interventions consistent with PCAD, and 4) consultations
      requested. Nine of 27 (33%) patients on the Oncology/Geriatrics units and all 50
      patients who died on the palliative care/hospice unit were placed on PCAD. During
      the PCAD intervention, dying patients who resided on Geriatrics, Oncology and
      palliative care/hospice units were more likely to have DNR orders than the
      comparison units, whereas the comparison units were more likely to use "morphine
      infusions" and cardiopulmonary resuscitation than the units that received the
      PCAD intervention. The mean number of symptoms assessed increased significantly
      in all units (P < 0.001 for all comparisons). The number of problematic symptoms
      identified (P=0.014) and the number of interventions consistent with PCAD
      increased only on the palliative care/hospice unit (P=0.021). The number of
      medical consultations declined on all units and reached significance on the
      Geriatrics and Oncology units (P=0.037). Although these results reflect less than
      one year of the PCAD intervention and must be considered preliminary, they
      suggest that 1) a clinical pathway such as PCAD can serve as a managerial and
      educational tool to improve the care of the imminently dying inpatient; 2) a PCAD
      clinical pathway can be implemented on hospital units as a quality improvement
      initiative--a "PCAD intervention;" 3) a PCAD intervention can change outcomes in
      a positive direction, as measured using a chart audit tool; 4) a PCAD
      intervention can promote aggressive symptom assessment and treatment when goals
      of care are aimed at comfort; and 5) changes may occur in units that do not
      directly receive the intervention, a phenomenon that suggests the possibility of
      diffusion. Further study of this systems-oriented approach to change is warranted
      and should include direct assessment of patient and family outcomes, as well as
      measures of process.

PMID- 15963862
TI  - Pilot of a pathway to improve the care of imminently dying oncology inpatients in
      a Veterans Affairs Medical Center.
AB  - We report on the implementation of a previously developed clinical pathway for
      terminally ill patients, Palliative Care for Advanced Disease (PCAD), on a
      Veterans Administration (VA) acute care oncology unit, comparing processes of
      care and outcomes for patients on and off the pathway. The PCAD pathway is
      designed to identify imminently dying patients, review care goals, respect
      patients' wishes, assess and manage symptoms, address spirituality, and support
      family members. Retrospective chart reviews from 15 patients who died on PCAD, 14
      patients who died on general wards during the same time, and 10 oncology unit
      patients who died prior to PCAD revealed that PCAD patients were more likely to
      have documentation of care goals and plans of comfort care (P=0.0001), fewer
      interventions, and more symptoms assessed (P=0.004), and more symptoms managed
      according to PCAD guidelines (P=0.02). Implementation of PCAD improved care of
      dying inpatients by increasing documentation of goals and plans of care,
      improving symptom assessment and management, and decreasing interventions at the
      end of life.

PMID- 15963863
TI  - A comparison between telephone and bedside consultations given by palliative care
      consultation teams in the Netherlands: results from a two-year nationwide
      registration.
AB  - Palliative Care Consultation (PCC) teams in The Netherlands give support to
      professional caregivers in palliative care. In contrast to many other countries,
      consultants only give advice. They do not give prescriptions. Most consultations
      are given by phone; in some, the consultant also visits the patient. For two
      years, the PCC teams registered all consultations prospectively on a standard
      registration form in a nationwide database. The aim of this study was to obtain
      more insight into the possible differences between telephone and bedsides
      consultations with regard to characteristics of consultants, requesting
      caregivers, and the patients, as well as the number and kind of problems
      discussed. The data demonstrate that bedside consultations show more variety in
      requesting caregivers and are conducted more often for patients. Bedside
      consultations also addressed a higher number of problems and a wider range of
      domains (e.g., psychological, spiritual, daily functioning, and support for
      informal caregivers). These results suggest that bedside consultations have a
      surplus value compared to telephone consultations. More rigorous study is needed
      to compare the relative merits of different methods of consultations in
      palliative care.

PMID- 15963864
TI  - Use of upper limb exercise to assess breathlessness in patients with cancer:
      tolerability, repeatability, and sensitivity.
AB  - We report the development of an arm exercise test to assess breathlessness in
      patients with lung cancer who are breathless at low levels of exertion. Exercise
      consisted of raising the arm over 40 cm, either the dominant arm only (n=10) or
      both arms alternating at minute intervals (n=12). Subjects breathed through a
      mouthpiece, and ventilation (VE) and oxygen uptake (VO(2)) were measured.
      Following familiarization, three tests were performed over one week to explore
      repeatability, and sensitivity was assessed in a fourth test. Arm exercise was
      generally well tolerated and increased breathlessness, VE, and VO(2). The
      commonest factor limiting exercise was arm fatigue, although four patients in the
      two-arm test also reported breathlessness. Repeatability for breathlessness score
      and VE was best in the two-arm test. The added resistance used to assess
      sensitivity could not be detected. The two-arm test offers a potential means of
      assessing the effects of an intervention on breathlessness and E in patients for
      whom a cycle or treadmill exercise test is unsuitable.

PMID- 15963865
TI  - Association between symptom distress and survival in outpatients seen in a
      palliative care cancer center.
AB  - Clinical observation and preliminary reports suggest that higher scores for
      symptoms such as pain may be associated with shorter survival. We undertook a
      survival analysis to determine whether symptom expression in outpatients with
      complex cancer is related to the duration of their survival. Participants were
      225 outpatients with cancer evaluated in our comprehensive cancer center for pain
      management or palliative care over a 10-week period ending June 2000. In addition
      to age and other clinical and demographic information, the patients completed the
      Anderson Symptom Assessment System (ASAS), which assesses pain, fatigue, nausea,
      depression, anxiety, drowsiness, shortness of breath (dyspnea), appetite, sleep,
      and feeling of well-being on a 0-10 scale. Univariate analyses showed that higher
      symptoms of dyspnea, drowsiness, problems with appetite, and nausea were
      significantly associated with shorter survival whereas pain, depression and other
      ASAS items were not. In multivariate analyses, only higher levels of dyspnea and
      drowsiness showed a significant association (P=0.01 and P=0.02, respectively)
      with shorter survival. Knowledge about these symptoms may be important in
      formulating adaptive randomization techniques for clinical trials and for
      research concerning estimates of survival.

PMID- 15963866
TI  - Discrepancies and similarities in how patients with lung cancer and their
      professional and family caregivers assess symptom occurrence and symptom
      distress.
AB  - Historically, conceptual distinctions have not been made between the components
      of symptom experience--symptom distress and symptom occurrence--nor has the
      question of how distressing patients perceive different symptoms to be,
      irrespective of their current occurrence, been addressed. The aim of this study
      was to explore the hypothesis that there may be different patterns in
      discrepancies between how lung cancer patients and their caregivers assess
      symptom distress and in how they assess symptom occurrence. Thirty-three patient
      nurse dyads and 54 patient-family caregiver dyads assessed patients' symptom
      distress and symptom occurrence. Discrepancies with regard to how patients,
      nurses, and family caregivers assessed symptom distress and symptom occurrence
      were identified. Patients and caregivers were more in agreement about which
      symptoms might cause distress than about current symptom occurrence. Caregivers
      rated symptom occurrence as greater than patients. The findings highlight the
      need to further explore what symptom characteristics caregivers address when
      assessing patients' symptom experiences.

PMID- 15963867
TI  - Comparative efficacy of oral extended-release hydromorphone and immediate-release
      hydromorphone in patients with persistent moderate to severe pain: two randomized
      controlled trials.
AB  - Two multicenter, randomized, double-blind, crossover studies with identical
      designs evaluated the efficacy of oral extended-release hydromorphone (HHER)
      administered q24h compared with immediate-release hydromorphone (HHIR) dosed four
      times daily in patients with persistent moderate to severe pain. Patients
      titrated to a stable HHER dose were randomized to individualized doses of HHER or
      HHIR for 3 to 7 days before crossover to the second treatment. Primary efficacy
      end point was the mean of average pain intensity (API) scores, rated on a 0- to
      10-point numeric scale, over the last 2 days before the
      pharmacokinetics/pharmacodynamics day of each double-blind period. Difference
      between treatments (HHER - HHIR) in study 1 was 0.17 with a 90% confidence
      interval (CI) (-0.01, 0.34); in study 2, difference was 0.07 with a 90% CI (
      0.12, 0.26). There were no significant differences between treatments in API
      scores or amount of rescue medication used at any time interval within the 24
      hour dosing period. No reduction in pain control occurred in patients
      administered HHER at the end of the 24-hour dosing period. Most treatment
      emergent adverse events were opioid-related. In these studies, HHER administered
      q24h and HHIR dosed four times daily provided comparable analgesia at an
      equivalent total daily dose.

PMID- 15963868
TI  - Changes in medical and nursing care in cancer patients transferred from a
      palliative care team to a palliative care unit.
AB  - The primary aim of this study was to explore the changes in medical/nursing care
      in patients who transferred from a palliative care team (PCT) to a palliative
      care unit (PCU) in the same hospital, and to explore the reasons why new or
      modified interventions were required. This was a retrospective study of 50
      consecutive patients who were transferred from PCT to PCU in a 750-bed general
      hospital. A trained nurse performed a chart review and recorded the changes in 1)
      medical/nursing care, 2) help with decision-making within 48 hours after PCU
      admission, and 3) documentation of family and psycho-existential care. Group
      discussions among PCT and PCU staff members explored the potential reasons for
      the changes. Five patients were excluded due to admission periods of shorter than
      48 hours. The number of new/modified medical and nursing care interventions after
      PCU admission averaged 1.9 +/- 1.5 and 1.5 +/- 1.3 per patient, respectively. The
      most common medical treatments were: reduction in hydration volume, dose
      titration of opioids, change in opioid administration device, opioid rotation,
      and addition of NSAIDs and steroids. The most common nursing interventions were:
      allowing patient to take a bath, changing mattress, use of massage, and
      discontinuation of bronchial suctioning. In addition, PCU staff newly coordinated
      opportunities to discuss preferred end-of-life care with primary caregivers in
      38% of the cases, family members other than primary caregivers in 16%, and
      patients in 6.7%. The chart documentation of family care and psycho-existential
      care increased considerably after PCU admission. The chief reasons for these
      changes were: under-recognition of the problems and unavailability of treatments
      (pharmacological treatments), no intention to intervene and recommendations not
      followed by primary physicians (rehydration therapy), no intention to intervene
      (nursing care), and no intention to intervene and under-recognition of the
      problems (help with decision-making). These data demonstrate that many patients
      under PCT consultation receive new or modified interventions after PCU admission.
      Potentially useful strategies to strengthen the PCT interventions are:
      modification of intervention structure to minimize under-recognition of symptoms
      and decision making problems (e.g., use of standardized assessment tools, regular
      conferences), changes in the health care system to allow unlicensed drugs,
      clinical studies to clarify the benefits of artificial hydration therapy, and
      greater efforts to intervene in the areas of nursing care, help with decision
      making, family care, and psycho-existential care.

PMID- 15963869
TI  - Somatic symptoms in patients with chronic non-cancer-related and cancer-related
      pain.
AB  - This study describes and compares patients' reports of somatic symptoms and
      physicians' ratings of the same symptoms in patients with chronic non-cancer
      related and cancer-related pain. Ninety-seven patients with chronic non-cancer
      related pain and 100 patients with chronic cancer-related pain reported somatic
      symptoms using a newly developed checklist of somatic symptoms. Patients also
      completed the Brief Symptom Inventory-18, Courtland Emotional Control Inventory,
      Catastrophizing scale, two items from the Coping Strategies Questionnaire (one
      about efficacy to control and another about ability to decrease pain), and a
      numeric rating of average pain. After they completed medical histories and
      physical examinations on patients, physicians rated the degree to which the
      patients' reported somatic symptoms on the checklist were medically
      unexplainable. Over 80% of patients in both groups reported somatic symptoms that
      their physicians rated as not fully explainable. Strong associations existed
      between patient-reported somatic symptoms and negative mood states. For the
      majority of patients, results supported a concept of combined illness- and affect
      related pathology rather than one of pure somatoform disorder. Assessing
      patients' reports of somatic symptoms and negative mood states and incorporating
      physicians' ratings of level of medically unexplainable somatic symptoms were
      useful for distinguishing these diagnoses.

PMID- 15963870
TI  - Nebulized versus subcutaneous morphine for patients with cancer dyspnea: a
      preliminary study.
AB  - This study compared the effects of nebulized versus subcutaneous morphine on the
      intensity of dyspnea in cancer patients. Patients with a resting dyspnea
      intensity > or =3 on a 0-10 scale (0=no dyspnea, 10=worst possible dyspnea) who
      received regular oral or parenteral opioids were included. On day 1, patients
      received either subcutaneous (SC) morphine plus nebulized placebo or nebulized
      morphine plus SC placebo. On day 2, a crossover was made. Dyspnea intensity, side
      effects, and blinded preference of treatment were assessed. Eleven patients
      completed the study. Dyspnea decreased from a median of 5 (range, 3-8) to 3
      (range, 0-7) after SC morphine (P=0.025) and from 4 (range, 3-9) to 2 (range, 0
      9) after nebulized morphine (P=0.007). There was no significant difference in
      dyspnea intensity between nebulized and subcutaneous morphine at 60 minutes.
      Unfortunately, due to limited sample size, there was insufficient power to rule
      out a significant difference between both routes of administration. Nebulized
      morphine offered dyspnea relief similar to that of SC morphine. Larger randomized
      controlled trials in patients with both continuous dyspnea and earlier stages of
      dyspnea are justified.

PMID- 15963872
TI  - Epidemiology of chlamydial infection, gonorrhea, and trichomoniasis in the United
      States--2005.
AB  - The prevalence and incidence of chlamydial infection, gonorrhea, and
      trichomoniasis are unacceptably high in the United States. The prevalence of
      gonorrhea is substantially lower than chlamydial infection and trichomoniasis; in
      part, this is presumably due to the greater frequency of symptomatic disease. The
      disparity between racial/ethnic groups is considerable for each of these
      infections. Greater effort must be devoted to reducing this disparity and to
      understanding the underlying mechanisms of disease persistence in the United
      States.

PMID- 15963873
TI  - Modern day influences on sexual behavior.
AB  - To better understand temporal trends in sexual behavior and their determinants,
      it is important to look at the demographic and technologic context in which we
      live; both affect sexual behaviors. Mental disorders and CSA emerge as important
      correlates of high-risk sexual behaviors. The changing role and expectations of
      women-the result of major economic and social transformation-transform society
      further through changes to family and community structures. These changes occur
      alongside increasing inequality and upheavals in the world, all of which are more
      visible through increased mobility and communication in the "global village."
      Changes in sexual norms, relationships, abuse, and mental health are better
      understood in the context of this broad political background.

PMID- 15963874
TI  - Increasing rates of sexually transmitted diseases in homosexual men in Western
      europe and the United States: why?
AB  - The recent increases in acute STDs among MSM must be viewed in the context of a
      post-AIDS era that is characterized by demographic shifts,changing sexual
      attitudes, and rapidly changing social contexts. A key driver seems to be the
      growing prevalent pool of HIV-positive MSM for whom the crucial motivator for
      safer sex (primary HIV prevention) no longer exists and where, given the
      prevalence of seroconcordant sexual mixing, consider-able uncertainty and
      conflicting advice regarding the rationale and benefits for continued safer-sex
      practice are unclear [105,106]. Although it is tempting to ascribe these changes
      to increases in risk behavior, it is essential that the contexts in which the
      changes are occurring are also considered. It may also be appropriate to
      contemplate whether further changes to the social environment (eg, structural
      interventions) are a suitable adjunct to our traditional prevention activities
      that operate largely in isolation from each other. It seems natural to advocate
      that interventions that adopt holistic approaches to the sexual health of MSM and
      that address upstream factors such as mental health, drug use, discrimination,
      and internalized homophobia should be included in the efforts to create more
      healthy environments for MSM. However, there is still some way to go in
      identifying which of these upstream interventions are effective, how they may be
      implemented within or alongside existing health care systems, and what impact, if
      any, they are likely to have on STD transmission. Such interventions are also
      likely to belong on implementation time, require consider political will, and be
      extremely hard to evaluate, and the benefits may not be seen within the same
      generation in which they are implemented. Therefore, there must be confidence
      that this is the appropriate route of travel. The consistency of findings from
      across industrialized countries confirms an increasing connectivity within the
      global MSM community;a community that is decreasingly defined by geographic
      boundaries and, in the era of the Internet and easier foreign travel,
      increasingly linked by shared interests and social and sexual networks. This is
      powerfully demonstrated in the near-simultaneous syphilis and LGV outbreaks among
      MSM in Europe and the United States [29]. In this regard, greater collaboration
      between researchers and providers working with MSM indifferent countries is now
      required. More specifically, consideration should be given to creating closer
      partnerships between sentinel cities, such as London, New York, San Francisco,
      Berlin, Paris, and Amsterdam, that have large MSM populations and are likely to
      be emerging, or rapid diffusion sites for new social and sexual trends that may
      impact on disease transmission. There are many benefits to such cross-national
      working,including earlier recognition and improved response to emerging
      threats,sharing innovative practice, avoiding duplication of effort, and creating
      a united front for dealing with what must be considered a cause for concern
      domestically and globally.

PMID- 15963875
TI  - Mucopurulent cervicitis: no longer ignored, but still misunderstood.
AB  - The last decade has produced considerable advances in the diagnosis of the common
      etiologies of mucopurulent cervicitis (MPC), including Chlamydia trachomatis and
      Neisseria gonorrhoeae, and in the delineation of key aspects of their
      pathogenesis. Despite this, clear understanding of why these bacteria cause
      cervical inflammation in a minority of women who is infected with either organism
      is limited. Furthermore, many women who have MPC have neither of these infections
      detected, even when highly sensitive diagnostic tests are used. This article
      describes current data regarding this common condition, and charts new
      developments that might inform a more comprehensive understanding of MPC and its
      management, and of the more subtle signs of cervical inflammation that may impact
      women's susceptibility to a variety of infectious diseases, including HIV-1.

PMID- 15963876
TI  - Fluoroquinolone-resistant Neisseria gonorrhoeae: the inevitable epidemic.
AB  - The worldwide incidence of fluoroquinolone-resistant Neisseria gonorrhoeae has
      increased dramatically in the last few years. Single doses of fluoroquinolones
      can no longer be used to treat N gonorrhoeae infections acquired in the Far East,
      parts of the Middle East, the Pacific Islands, and parts of Western Europe and
      the United States. Although California and Hawaii account for most of the current
      United States cases, the increased incidence of FQR in some high-risk groups
      independent of geography heralds an imminent spread of drug-resistant strains
      throughout the rest of the population. The use of molecular tests has
      revolutionized the diagnostic field in STIs. The main limitation of their
      application in N gonorrhoeae testing has been the loss of culture specimens that
      allow antimicrobial sensitivity testing. New molecular methods have made it
      possible to detect antimicrobial resistance without the use of live organisms.
      These tests hold the promise of improving epidemiologic tracking of N gonorrhoeae
      drug resistance, leading to better patient management at the local level. The
      loss of fluoroquinolones limits available oral regimens to a single CDC
      recommended antibiotic, cefixime. Oral, inexpensive, single-dose alternatives are
      needed to ensure continued therapeutic success.

PMID- 15963877
TI  - Nucleic acid amplification tests for gonorrhea and chlamydia: practice and
      applications.
AB  - Nucleic acid amplification tests (NAATs), which are highly sensitive and
      specific, have provided the ability to use alternative sam-ple types for the
      diagnosis of sexually transmitted infections (STIs). Self-collected genital
      specimens, such as urine or even vaginal swabs, can now be accurately used to
      diagnose gonorrhea or chlamydia infections. In many cases, use of these sample
      types can decrease the necessity for a clinician to perform a pelvic examination
      on women or to collect a urethral swab from men, thus extending the diagnostic
      capability for detecting these infections to nonclinic screening venues. As most
      chlamydia infections and many gonorrhea infections are asymptomatic, the use of
      NAATs for self-collected samples greatly increases the types and numbers of
      patients that can be screened outside of clinic settings. Self-sampling also
      allows clinicians to easily screen patients in the clinic for STIs who are not
      presenting for pelvic or urogenital examinations. The application of NAATs to
      self-collected specimens has the potential to augment public health programs
      designed to control the epidemic of STIs in the community.

PMID- 15963878
TI  - What's new in bacterial vaginosis and trichomoniasis?
AB  - The use of biochemical profiles and new molecular microbiologic methodologies is
      transforming our understanding of BV. Most important is the recognition of
      different subgroups of women who have BV who are at variable risk of certain
      obstetric and gynecologic complications. New diagnostic tests may soon be
      available that will allow women to test self-obtained specimens. Treatment of BV
      has lagged, although innovative methods appear to be helpful in managing
      recurrent diseases.

PMID- 15963879
TI  - Is Mycoplasma genitalium a cause of pelvic inflammatory disease?
AB  - The evidence for M genitalium as a sexually acquired infection in women is
      strong, and the organism has been associated with cervicitis and urethritis. In
      vitro evidence supports the concept that M genitalium causes inflammation in the
      fallopian tube epithelium, and animal studies have demonstrated the potential for
      infection to spread from the lower to the upper genital tract. Serologic data in
      humans who have PID are somewhat conflicting, but studies in infertile women
      suggest a link between M genitalium and tubal damage. The organism has also been
      isolated in the endometrium and fallopian tubes of women who have PID. The
      evidence is therefore accumulating that M genitalium is a cause of PID, and the
      assessment of reliable tests to further investigate the importance of this
      organism and its relevance in designing future treatment strategies is urgently
      needed.

PMID- 15963880
TI  - Developments in STD/HIV interactions: the intertwining epidemics of HIV and HSV
      2.
AB  - Antiviral agents aimed at treating HSV-2 chronically infected individuals have
      proven to be effective in the prevention of symptomatic genital herpes and the
      reduction of viral shedding. These agents play a key role in current HIV
      prevention trials that will assess the role of suppression of HSV-2 infection on
      the risk for HIV acquisition and transmission. An added clinical benefit of
      treating HSV-2/HIV-coinfected individuals is the potential survival benefit, as
      suggested by earlier studies and by the recent findings that HSV-2/HIV dually
      infected individuals have higher viral loads. The results of the current HSV-2
      suppression trials may provide additional tools to fight the global spread of HIV
      infection. Treatment of HSV-2/HIV dually infected individuals may prove to be a
      low-cost intervention to improve clinical outcomes and delay the need for
      antiretroviral therapy.

PMID- 15963881
TI  - Managing patients with genital herpes and their sexual partners.
AB  - There is increasing recognition of the growing size and significance of the
      genital herpes epidemic. Recent developments in the wide-scale availability of
      type-specific herpes simplex virus (HSV) sero-logic assays have meant that many
      previously undiagnosed mild,atypical, and subclinical infections may now be
      diagnosed with some degree of confidence without the use of Western blots. The
      value of such diagnostics is controversial. However, the importance of HSV with
      its facilitation of HIV transmission and acquisition, the availability of various
      preventative strategies for limiting vertical HSV transmission, and the growing
      evidence that condoms, some educational and counseling interventions, and
      antiviral therapies may limit sexual transmission, have challenged many of the
      arguments against wider testing of the population.

PMID- 15963882
TI  - Diagnosis and management of oncogenic cervical human papillomavirus infection.
AB  - Cervical HPV infection should be managed less as a typical STI and more as a
      strong risk factor predisposing to cervical cancer development. HPV infection is
      undeniably transmitted predominately through sexual contact.However, the fact
      that more than 80% of women followed over time will acquire at least one HR-HPV
      infection reflects the ubiquitous nature of the infection and the ease of
      transmission. Although the behavioral profiles typically associated with an
      increased risk for STI (including lifetime partner number, age at first
      intercourse, and so forth) will certainly lead to an increased risk for HPV
      detection, there is a high absolute prevalence of HPV even among women who have
      few lifetime sex partners. It could be argued that to counsel patients for an HPV
      infection as an STI would be counterproductive, as short of absolute abstinence,
      the prevention of infection is difficult and treatment options, short of
      excisional procedures for neoplasia, are limited. The real promise held in this
      area is the availability of an apparently highly effective prophylactic HPV
      vaccine, targeting at least HPV 16, 18, 6, and 11[33,34]. This vaccine cocktail,
      if it achieved 100% coverage, could theoretically prevent 50% to 70% of invasive
      cervical cancers and most genital warts. Vaccination will be required among women
      before initiation of sexual contact, presumably among girls 10 to 13 years of
      age. Many programmatic issues remain regarding the implementation of HPV vaccine
      programs, including the marketing of the vaccine as STI or cancer prevention,as
      reviewed in detail by Gravitt and Shah [72]. Even in the era of potentially
      effective vaccines, screening for cervical cancer is likely to remain a priority
      in cervical cancer prevention programs for at least several decades. Vaccine
      trials have proven high short-term efficacy; however, these effects were clearly
      type-specific and antibody titers gradually decrease postvaccination. It is
      unclear whether the protection will remain over an individual's lifetime without
      vaccine booster, and oncogenic HPV infections not targeted by vaccination will
      continue to contribute to risk for development of cervical intraepithelial
      neoplasia and cancer. Therefore, although the public health success of HPV
      vaccination is undoubtedly promising, the role of cervical cancer screening as a
      secondary prevention effort should not be trivialized. In fact, the nature of
      screening programs should continue to be reevaluated in the context of effective
      but limited spectrum vaccines.

PMID- 15963883
TI  - Counseling the patient who has genital herpes or genital human papillomavirus
      infection.
AB  - Educational counseling has an important role in managing patients who have viral
      STIs, such as genital herpes and genital HPV infections. Given the lack of a
      curative therapy for both, patients may require long-term management and may need
      to be attentive to recurring symptoms. In addition, both diagnoses may raise
      issues of persisting infectiousness along with a need for patient counseling
      about the potential risk to partners and risk reduction strategies. Lastly,
      dozens of published papers over the years describe potential psychosocial
      sequelae for patients who have genital herpes, and there is a growing
      psychosocial literature on genital HPV as well. Clinicians can make a significant
      difference in patient adjustment to the diagnosis of an STI, and addressing these
      challenging issues will benefit patients greatly.

PMID- 15963884
TI  - Progress in vaccines for sexually transmitted diseases.
AB  - The development pipeline for vaccines to control sexually transmitted infections
      holds greater promise than ever before. Preclinical studies are encouraging in
      the development of chlamydia and gonococcal vaccines, and for the first time,
      recent clinical trials have shown the feasibility of creating vaccines to control
      genital herpes and cervical human papillomavirus infections. Behavioral research
      suggests that these vaccines will likely find acceptance among health care
      providers and consumers.

PMID- 15963885
TI  - Sexually transmitted disease care in managed care organizations.
AB  - Most STD cases in the United States are managed in health sectors dominated by
      commercial and Medicaid MCOs. To sustain the recent declines in bacterial STD
      incidence in the United States and to control expansion of the prevalent viral
      STD, MCOs will need to contribute substantially to control efforts. Applied
      researchers and quality improvement specialists must work with clinicians,
      patients, and health systems to develop and scale-up interventions to improve STD
      prevention and control.

PMID- 15963886
TI  - Innovative approaches to the prevention and control of bacterial sexually
      transmitted infections.
AB  - Bacterial STI continues to be a major problem in developed nations. Research and
      evolving standards of public health practice are cause for optimism and concern.
      Innovations in case-finding and treatment, particularly the application of NAATs
      to test for chlamydial infection in nonclinical settings, are successes that
      merit more widespread application. EPT, selective STI screening in men, and
      rescreening are all promising, but are not yet in widespread use and may face
      significant operational barriers. To date, public health efforts to alter sexual
      behavior, at least through specific interventions, are more discouraging.
      Although some behavioral interventions have been effective, none has been widely
      instituted. Moreover, the likelihood that existing behavioral interventions will
      be widely applied seems remote. Future research efforts in this area will need to
      focus less on proof-of-concept efficacy trials and more on developing and testing
      sustainable, cost-effective interventions that focus on those at greatest risk
      and that can be scaled-up within the existing public health infrastructure.

PMID- 15963887
TI  - Behavioral interventions--rationale, measurement, and effectiveness.
AB  - Effective STD and HIV prevention requires synergism of individual-based
      prevention behaviors and societal/structural supports that will promote and
      maintain these behaviors. We should also expect the unexpected. STD rates in gay
      men have risen after effective prevention of HIV/STD in gay men and effective
      antiretroviral therapy. New drugs of abuse, such as methamphetamine ("crystal
      meth"), have induced risky sexual behaviors in gay and heterosexual communities.
      Economic dislocation in Eastern Europe has resulted in trafficking of commercial
      sex workers to Europe, the Mideast, and Asia, all with the potential for STD and
      HIV spread. James Curran, formerly director of the HIV epidemiology and
      prevention effort at the CDC, has written: It is ironic that the two clearest
      examples of large-scale success in HIV prevention-reduction in HIV transmission
      in gay men in the United States and national declines in HIV incidence in
      Thailand-arise in societies/communities known in their own way for sexual
      openness....the openness in both communities provided the environment to make the
      powerful revolutionary changes needed. In Africa, the powerful voice of President
      Museveni of Uganda has also encouraged candor about sexual risk-taking and
      facilitated that nation's encouraging early success in reducing HIV
      prevalence...Unfortunately, most of the world remains unable or unwilling to deal
      frankly and consistently with sexuality despite the considerable risks of HIV
      infection in many communities. There is a worldwide sexual hangup hampering HIV
      prevention efforts.

PMID- 15963888
TI  - Evolutionary aspects of whole-genome biology.
AB  - A decade of access to whole-genome sequences has been increasingly revealing
      about the informational network relating all living organisms. Although at one
      point there was concern that extensive horizontal gene transfer might hopelessly
      muddle phylogenies, it has not proved a severe hindrance. The melding of sequence
      and structural information is being used to great advantage, and the prospect
      exists that some of the earliest aspects of life on Earth can be reconstructed,
      including the invention of biosynthetic and metabolic pathways. Still, some
      fundamental phylogenetic problems remain, including determining the root--if
      there is one--of the historical relationship between Archaea, Bacteria and
      Eukarya.

PMID- 15963889
TI  - Multiple sequence alignments.
AB  - Multiple sequence alignments are very widely used in all areas of DNA and protein
      sequence analysis. The main methods that are still in use are based on
      'progressive alignment' and date from the mid to late 1980s. Recently, some
      dramatic improvements have been made to the methodology with respect either to
      speed and capacity to deal with large numbers of sequences or to accuracy. There
      have also been some practical advances concerning how to combine three
      dimensional structural information with primary sequences to give more accurate
      alignments, when structures are available.

PMID- 15963890
TI  - Predicting protein function from sequence and structural data.
AB  - When a protein's function cannot be experimentally determined, it can often be
      inferred from sequence similarity. Should this process fail, analysis of the
      protein structure can provide functional clues or confirm tentative functional
      assignments inferred from the sequence. Many structure-based approaches exist
      (e.g. fold similarity, three-dimensional templates), but as no single method can
      be expected to be successful in all cases, a more prudent approach involves
      combining multiple methods. Several automated servers that integrate evidence
      from multiple sources have been released this year and particular improvements
      have been seen with methods utilizing the Gene Ontology functional annotation
      schema.

PMID- 15963891
TI  - RNA structure: the long and the short of it.
AB  - The database of RNA structure has grown tremendously since the crystal structure
      analyses of ribosomal subunits in 2000-2001. During the past year, the trend
      toward determining the structure of large, complex biological RNAs has
      accelerated, with the analysis of three intact group I introns, A- and B-type
      ribonuclease P RNAs, a riboswitch-substrate complex and other structures. The
      growing database of RNA structures, coupled with efforts directed at the
      standardization of nomenclature and classification of motifs, has resulted in the
      identification and characterization of numerous RNA secondary and tertiary
      structure motifs. Because a large proportion of RNA structure can now be shown to
      be composed of these recurring structural motifs, a view of RNA as a modular
      structure built from a combination of these building blocks and tertiary linkers
      is beginning to emerge. At the same time, however, more detailed analysis of
      water, metal, ligand and protein binding to RNA is revealing the effect of these
      moieties on folding and structure formation. The balance between the views of RNA
      structure either as strictly a construct of preformed building blocks linked in a
      limited number of ways or as a flexible polymer assuming a global fold influenced
      by its environment will be the focus of current and future RNA structural
      biology.

PMID- 15963892
TI  - Multiple modes of RNA recognition by zinc finger proteins.
AB  - Zinc finger proteins are generally thought of as DNA-binding transcription
      factors; however, certain classes of zinc finger proteins, including the common
      C(2)H(2) zinc fingers, function as RNA-binding proteins. Recent structural
      studies of the C(2)H(2) zinc fingers of transcription factor IIIA (TFIIIA) and
      the CCCH zinc fingers of Tis11d in complex with their RNA targets have revealed
      new modes of zinc finger interaction with nucleic acid. The three C(2)H(2) zinc
      fingers of TFIIIA use two modes of RNA recognition that differ from the classical
      mode of DNA recognition, whereas the CCCH zinc fingers of Tis11d recognize
      specific AU-rich sequences through backbone atom interaction with the Watson
      Crick edges of the adenine and uracil bases.

PMID- 15963893
TI  - Extranodal nasal type NK/T-cell lymphoma: elucidating clinical prognostic factors
      for risk-based stratification of therapy.
AB  - The purpose of this study was to define distinctive clinical features of "nasal"
      and "nasal-type" NK/T cell lymphomas by assessing prognostic factors. The
      anatomic definition of extranasal NK/T cell lymphoma has been vague resulting in
      variable definitions of extranasal sites by different groups. We analysed the
      clinical behavior of 90 NK/T cell lymphoma patients and attempted to elucidate
      the prognostic factors for risk-based stratification of therapy. We observed no
      significant difference between "nasal" and "nasal-type" NK/T cell lymphomas in
      regards to clinical features and survival using the conventional anatomic
      classification. We suggest the categorisation of the two subtypes of NK/T cell
      lymphoma as follows: UNKTL (upper aerodigestive tract NK/T cell lymphoma)
      including all lymphomas confined to nasal cavity, nasopharynx, and the upper
      aerodigestive tract and EUNKTL (extra-upper aerodigestive tract NK/T cell
      lymphoma) group to include all sites other than the UNKTL group. The EUNKTL group
      in this study had advanced stage at diagnosis, higher LDH, higher IPI score,
      poorer performance and inferior response to the anthracycline-based chemotherapy
      with statistical significance. There was a significant difference in survival
      rate between EUNKTL and UNKTL group (20.0%, 54.0%, respectively, P = 0.0068).
      More aggressive treatment should be sought for this particular group of patients
      for EUNKTL patients.

PMID- 15963894
TI  - Bloodstream infections and invasive mycoses in children undergoing acute
      leukaemia treatment: a 13-year experience at a single Italian institution.
AB  - The incidence rate (IR) of bloodstream infections (BI) and invasive mycoses (IM)
      during chemotherapy for paediatric acute lymphoblastic (ALL) or non-lymphoblastic
      leukaemias (AnLL) was evaluated for 153 BI and 22 IM diagnosed during 143,668
      patient-days at risk from January 1988 to December 2000. IR, the number of
      episodes/100 days at risk, was 0.315 for AnLL and 0.092 for ALL (P < 0.001) with
      significant changes reflecting the intensity of anti-ALL chemotherapy. IR was
      0.097 for first-line less intensive, 0.136 during first-line intensive, 0.261
      during second-line therapy (P < 0.001), and 0.021 during maintenance. During
      intensive chemotherapy, the IR for BI was 0.134 in ALL with 0.087 for first-line
      less intensive therapy, 0.110 for first-line intensive, 0.230 for second-line
      intensive therapy (P < 0.001) and 0.274 in AnLL (P = 0.001). IR was 0.021 in ALL
      and 0.048 in AnLL (P = 0.034) for IM. In conclusion, there is a correlation
      between intensity of chemotherapy and rate of infections in paediatric acute
      leukaemias.

PMID- 15963895
TI  - Preventing underage alcohol use: where do we go from here?

PMID- 15963896
TI  - School-based smoking prevention research.

PMID- 15963897
TI  - School-based smoking prevention research.

PMID- 15963898
TI  - School-based smoking prevention research.

PMID- 15963901
TI  - Remarks on the changing nature of inquiry.

PMID- 15963902
TI  - Emotional distress, alcohol use, and peer violence among Mexican-American and
      European-American adolescents.
AB  - PURPOSE: To examine the longitudinal relations among emotional distress, alcohol
      use, and peer-directed violence. METHODS: Interviews were conducted with 297
      young adolescents, randomly selected from the membership lists of a large health
      maintenance organization. Participants were aged 12-15 years, 55% were male, and
      were either Mexican-American (n = 147) or European-American (n = 150).
      Adolescents reported on their emotional distress at baseline, and on their
      alcohol use at 6-month follow-up. At 12-month follow-up, they reported on their
      involvement in peer violence, including physical fights and weapons exposure.
      Data were analyzed using analysis of variance and multiple linear regression.
      RESULTS: Boys reported being in more physical fights than girls. Mexican
      Americans reported more weapons exposure than European-Americans, but when
      controlling for socioeconomic status and age, these differences disappeared. For
      both ethnic groups, adolescents who experienced greater emotional distress later
      reported more alcohol use and more involvement in peer violence. For Mexican
      American adolescents, alcohol use mediated the relations between emotional
      distress and both physical fights and weapons exposure. For European-Americans,
      alcohol use mediated the relations between emotional distress and physical
      fights, but only marginally mediated the relation between emotional distress and
      weapons exposure. CONCLUSIONS: Adolescents who experience greater emotional
      distress are at heightened risk for using alcohol and, in turn, for becoming
      involved in peer violence. Mexican-American adolescents in particular may use
      alcohol as a means of coping with emotional distress, and alcohol use appears to
      facilitate involvement in peer violence.

PMID- 15963903
TI  - Pathways to adolescent alcohol use: family environment, peer influence, and
      parental expectations.
AB  - PURPOSE: This study was conducted to examine the relationships among family
      environment, peer influence, stress, self-efficacy, and adolescent alcohol use
      and to test for the potential moderating effects of parental expectations
      regarding adolescent alcohol use. METHODS: Data were obtained from questionnaires
      completed by high school students (n = 2573) participating in a longitudinal
      study of substance use and other problem behaviors. Variables were lagged across
      three time points to reflect a causal sequence relating family environment to
      adolescent alcohol use through self-efficacy, peer influence, and stress. A
      latent measure of family environment included adolescents' perceptions of
      parental acceptance, parental monitoring, and communication with parents. The
      latent measure of peer influence included use of alcohol by same-age peers and
      friends and friends' approval of alcohol use. Observed scale scores were used for
      self-efficacy and stress measures, and the latent measure of alcohol behaviors
      included quantity, frequency, and associated problems. RESULTS: Structural
      equation modeling indicated good model fit, chi(2) (144) = 831.69, p < .001,
      comparative fit index (CFI) = .992, root mean square error of approximation
      (RMSEA) = .043 (.040, .046). Family environment exerted significant indirect
      effects on adolescent alcohol use through peer influence, self-efficacy, and
      stress, and parental expectations significantly moderated all structural paths.
      CONCLUSIONS: Parental expectations of adolescent alcohol use significantly
      moderated all structural relationships, and greater parental disapproval was
      associated with less involvement with friends and peers who use alcohol, less
      peer influence to use alcohol, greater self-efficacy for avoiding alcohol use,
      and lower subsequent alcohol use and related problems.

PMID- 15963904
TI  - Saturated in beer: awareness of beer advertising in late childhood and
      adolescence.
AB  - PURPOSE: The purpose of this study was to examine exposure, response to, and
      awareness of beer advertising in 2 age groups, including awareness of a Budweiser
      advertisement (ad) that portrayed lizards and an animated ferret. METHODS: In the
      spring of 2000, 1,996 fourth graders and 1,525 ninth graders attending 1 of 60
      South Dakota schools participated in an in-school survey. Several indicators of
      advertising awareness, exposure, and response were assessed: recognition, product
      naming, brand naming, and liking in response to stills drawn from 4 masked
      television beer ads, listing of beer brands, exposure, attention to, and
      skepticism toward television beer ads. RESULTS: Fourteen percent of 4th graders
      and 20% of 9th graders recognized at least 3 of 4 sample beer ads. Seventy-five
      percent of 4th graders and 87% of 9th graders recognized the Budweiser ferret ad;
      about one in three 4th graders could name the brand it advertised, whereas more
      than three in four 9th graders could do so. When asked to list as many beer
      brands as they could, almost 29% of 4th graders listed 3 or more beer brands and
      82% of 9th graders did so. Ninth graders liked beer advertisements more and paid
      greater attention to them, but 4th graders were exposed to them more often.
      CONCLUSION: Television beer ads result in high levels of beer advertising
      awareness in children as young as age 9, and even higher awareness among 14-year
      olds. Practices that expose or appeal to youth, including use of animated
      characters, should be avoided by beer advertisers.

PMID- 15963905
TI  - Heavy episodic drinking and sensation seeking in adolescents as predictors of
      harmful driving and celebrating behaviors: implications for prevention.
AB  - OBJECTIVES: Effectiveness of strategies to counter injurious risk-taking in
      adolescents depends on the degree to which behaviors are modifiable or intrinsic
      to a sensation-seeking personality. Alcohol consumption is often targeted because
      it is seen as a modifiable determinant. This study sought to clarify the relative
      importance of engagement in heavy episodic drinking (HED) independently of
      sensation-seeking tendency (SS), as a predictor of potentially harmful (and
      protective) behaviors. METHODS: A written survey was administered to students
      aged 15-17 years in 40 high schools in New South Wales (NSW), Australia to
      measure HED, SS, and harmful and protective behaviors associated with drug and
      alcohol use, driving, and celebrating. RESULTS: Of 2705 respondents, 60% reported
      HED, 36% failed to wear a seatbelt, 23% rode with an alcohol-impaired driver, 23%
      rode with a drug-impaired driver and 9% had been alcohol impaired while driving.
      Two-thirds (65%) had engaged in harmful behaviors and 99% had engaged in
      protective behaviors while celebrating. SS, gender, income, and age were
      significant predictors of HED. HED and SS were significant, independent
      predictors of every harmful or protective behavior. HED had the greatest effect
      on harmful celebrating behaviors, riding with an alcohol-impaired acquaintance,
      and riding with a drug-impaired driver. HED had a stronger effect than SS, for
      alcohol-impaired driving, riding with an alcohol-impaired acquaintance, riding
      with a drug-impaired driver, and harmful celebrating behaviors. CONCLUSIONS: The
      vast majority of adolescents who are low to average sensation seekers may benefit
      from population-based prevention strategies emphasizing that decisions leading to
      harmful outcomes are more likely if they engage in HED.

PMID- 15963906
TI  - Nonmedical use of prescription opioids among teenagers in the United States:
      trends and correlates.
AB  - PURPOSE: This article reports on trends and correlates of the nonmedical use of
      prescription opioids among youth. METHODS: Secondary analyses of data from the
      National Survey on Drug Use and Health were performed on youths, ages 12 to 17.
      RESULTS: Analyses revealed evidence of an emerging epidemic of opioid misuse
      among teenagers. Sub-groups of youth at particularly high risk include females,
      blacks, those of lower socio-economic status, and those who hold favorable
      attitudes toward illicit drugs, have detached parents, or have friends who use
      illicit drugs. Respondents' own use of other illicit drugs is the strongest
      predictor of their nonmedical use of prescription opioids. CONCLUSIONS:
      Nonmedical use of prescription opioids is a recurrent epidemic and valuable
      lessons from past epidemics of this nature can be learned if historical data are
      studied. Prevention campaigns should target groups at risk for substance abuse
      and focus on improving family bonds and peer-resistance skills.

PMID- 15963907
TI  - Use of nitrite inhalants ("poppers") among American youth.
AB  - PURPOSE: We examined the patterns and correlates of nitrite inhalant use among
      adolescents aged 12 to 17 years. METHODS: Study data were drawn from the 2000 and
      2001 National Household Surveys on Drug Abuse. Logistic regression was used to
      identify the characteristics associated with nitrite inhalant use. RESULTS: Among
      adolescents aged 12 to 17 years, 1.5% reported any lifetime use of nitrite
      inhalants. The prevalence of lifetime nitrite inhalant use increased to 12% and
      14% among adolescents who were dependent on alcohol and any drug in the past
      year, respectively. Many nitrite inhalant users used at least three other types
      of inhalants (68%) and also met the criteria for alcohol (33%) and drug (35%)
      abuse or dependence. Increased odds of nitrite inhalant use were associated with
      residing in nonmetropolitan areas, recent utilization of mental health services,
      delinquent behaviors, past year alcohol and drug abuse and dependence, and multi
      drug use. CONCLUSIONS: Adolescents who had used nitrite inhalants at least once
      in their lifetime tend to engage in delinquent activities and report co-occurring
      multiple drug abuse and mental health problems in the past year.

PMID- 15963908
TI  - An evaluation of school-level factors used in a successful school-based hepatitis
      B immunization initiative.
AB  - PURPOSE: To examine the effect of different school-level factors on the percent
      return of consent or refusal forms, the percent student participation/enrollment
      rate, and the percent completion rate of all 3 immunizations in the vaccination
      series in a school-based hepatitis B immunization initiative. METHODS: The
      Houston Hepatitis B Immunization Initiative (HBII) was conducted from 1998
      through 2001 to provide free hepatitis B immunizations to elementary school
      students in low socioeconomic areas. At the end of each academic school year, the
      nurse from each school participating in the initiative was asked to complete a
      survey evaluating the different strategies utilized in each school to aid in the
      program's success. The effect of different organizational methods on rate of
      return of consent/refusal forms, participation rates, and immunization completion
      rates from the program year 1999-2000 was determined using frequencies, Mann
      Whitney analyses, Kruskal-Wallis analyses, and Spearman's correlations. RESULTS:
      An increase in percent return of signed consent/refusal forms was more likely
      when teachers helped in publicity/promotion (p = .012) and educational packet
      distribution (p = .041). Additionally, when teachers assumed responsibility for
      collecting the forms, the percent return of signed consent/refusal forms (p =
      .018) and the percent of students receiving all 3 vaccines in the series through
      HBII (p = .030) were more likely to increase. An increase in signed
      consent/refusal forms returned was also associated with increased rates of
      student participation in the program for each school. In schools where students
      helped specifically with educational packet distribution (p = .039), the percent
      of students receiving at least 1 vaccine dose from the program was more likely to
      be higher. CONCLUSIONS: The involvement of teachers in vaccination programs is
      very important for program success, especially in the enrollment and return of
      consent/refusal form phases of immunization initiatives. Student involvement may
      empower the students and encourage other students to participate in the program.
      Future school-based immunization initiatives can utilize these data to
      incorporate the most effective school-level factors into their programs to
      maximize the number of students immunized.

PMID- 15963909
TI  - Understanding the role of perceived severity in STD-related care-seeking delays.
AB  - PURPOSE: To gain a more in-depth understanding of the relationship between
      perceived severity of symptoms and STD-related care-seeking behavior among
      adolescent African-American females in Baltimore City. METHODS: Twenty-one female
      adolescents were interviewed in depth to elicit their experiences with an STD in
      the previous 3 months. Comparisons were made between those who sought care on
      account of their symptoms and those who did not. RESULTS: High perceived
      seriousness about symptoms has both cognitive and emotional components that may
      function independently to either promote or delay STD-related care seeking.
      CONCLUSIONS: Both cognitive and emotional responses to STD symptoms must be
      considered when examining the effect of perceived severity on adolescents' STD
      related care-seeking behaviors.

PMID- 15963910
TI  - Relations between normative beliefs and initiation intentions toward cigarette,
      alcohol and marijuana.
AB  - PURPOSE: To examine the relations between normative beliefs and intentions to
      initiate cigarette, alcohol, and marijuana use among adolescents reporting no
      prior use. METHODS: An anonymous questionnaire was administered to 6,594 seventh-
      to twelfth-grade students in northeast Ohio. Separate analyses were conducted on
      sub-samples of respondents reporting no prior use of each substance. Within each
      of these 3 sub-samples, respondents were classified as holding high-risk
      intentions if they reported that they intended to begin using that particular
      substance within the next 6 months or were "not sure" of their intentions. Those
      reporting that they did not intend to start using a substance were classified as
      holding low-risk intentions. Multivariate logistic regression analyses examined
      the relations between normative beliefs and intention status (low- vs. high
      risk), while accounting for socio-demographic characteristics. RESULTS: Across
      all 3 substances, normative beliefs were stronger predictors of intention status
      than socio-demographic variables. Higher levels of perceived acceptability and
      perceived prevalence were associated with holding high-risk intentions. Normative
      belief measures assessing close friend and sibling reference groups were much
      more important in explaining intention status than those assessing other
      reference groups (e.g., same age peers). CONCLUSIONS: Among adolescents with no
      prior use, normative beliefs concerning close friends and siblings may play an
      important role in the catalysis and support of intentions to initiate substance
      use. These findings challenge the utility of primary prevention strategies that
      provide normative feedback based on rates of substance use among distal reference
      groups.

PMID- 15963911
TI  - Vitamin D deficiency in adolescent females.
AB  - PURPOSE: The purpose of this study was to estimate the incidence of low serum 25
      hydroxyvitamin D [25(OH)D] levels in adolescent girls and across racial groups
      and seasons. METHODS: Healthy postmenarcheal girls (12-18 years of age) were
      recruited for the study. Serum samples were assayed for 25(OH)D with a
      competitive protein binding assay (CPB) (Nichols Institute, San Clemente,
      California). RESULTS: The study included 370 girls (mean age, 15.5 +/- 1.6 y),
      with a mean serum 25(OH)D level of 53.7(29.0) nmol/L. Seventeen percent of the
      girls were found to be vitamin D deficient (serum 25(OH)D <or= 27.5 nmol/L) and
      54% were vitamin D insufficient (serum 25(OH)D <or= 50 nmol/L) using the CPB
      assay. There was a significant difference in mean serum 25(OH)D levels between
      the African-American girls (43.0 nmol/L) and non-African-American girls (72.2
      nmol/L) (p < .0001). Mean vitamin D levels were higher in the spring/summer
      months (60.2 nmol/L) compared with those obtained during the fall/winter months
      (52.8 nmol/L) (p < .01), and weight was correlated negatively with vitamin D
      levels (r = -.19) (p = .0002). CONCLUSIONS: For adolescent girls living in the
      northeastern United States, especially African-American girls, low 25(OH)D levels
      are a noteworthy concern because bone acquisition is crucial during this period
      of development.

PMID- 15963912
TI  - Assessment of iron status in adolescents: dietary, biochemical and lifestyle
      determinants.
AB  - PURPOSE: This study assessed the impact of dietary intake and lifestyle factors
      on iron status in adolescents. METHODS: Iron status, dietary intakes and relevant
      lifestyle behaviors of 396 healthy adolescents were assessed using food frequency
      questionnaires, a lifestyle survey, anthropometric measures, and blood analysis
      for serum ferritin, percent transferrin saturation, and serum hemoglobin levels.
      RESULTS: Six percent of the females in the sample were found to be iron
      deficient. The prevalence of iron deficiency anemia in the total female
      population was 3.4%. No males met the criteria for iron deficiency or iron
      deficiency anemia. Dietary iron intake exceeded the Estimated Average Requirement
      for all groups. However, iron intake was observed to be significantly higher in
      individuals with a healthy iron status, as compared with those who were
      considered iron deficient. CONCLUSIONS: The results counter the assertion that
      iron deficiency in developed countries is the result of low iron intakes. This
      study did not explore factors such as the type and bioavailability of dietary
      iron sources consumed by the participants. However, the authors speculate that
      these variables may have a greater impact on iron status than total dietary iron
      intakes or lifestyle determinants.

PMID- 15963913
TI  - Adolescent use of complementary therapies.
AB  - PURPOSE: Interest in alternative/complementary therapies (A/CTs) is on the rise,
      yet little is known about adolescents' use of A/CTs. The study purpose was to
      examine A/CT utilization patterns among a clinic-based sample of adolescents.
      METHODS: A cross-sectional survey of 401 adolescents, aged 12-18 years, was
      conducted in one Midwest urban adolescent ambulatory clinic in 2002. RESULTS:
      Overall, 68.1% of the adolescents reported using one or more A/CT; most commonly,
      herbal medicines (27.2%), massage therapy (26.7%), and megavitamins (21.7%). Use
      by friends and family was the primary influence for adolescent A/CT use; lack of
      familiarity was the greatest reason for nonuse (53.9%). Alleviation of physical
      pain (66.3%) was the most common desired health outcome. Few adolescents (13.8%)
      disclosed A/CT use to their health care providers. Insurance coverage was
      provided for 10.2% of the therapies and out-of-pocket costs averaged 67
      dollars/month. Age, race/ethnicity, having a health condition, taking
      medications, health responsibility, and work status were associated with overall
      A/CT use in bivariate analyses. Of these, only associations between A/CT use and
      race/ethnicity and health responsibility remained statistically significant after
      adjusting for the other variables. CONCLUSIONS: Use of A/CTs was common among
      these adolescents, yet very few disclosed their use to health care providers.
      Providers must ask about A/CT use to gain a more complete understanding of health
      practices among adolescents in clinical settings. Future research is needed to
      better understand representative patterns of A/CT use.

PMID- 15963914
TI  - Subjective evaluations of alcohol expectancies and their relevance to drinking
      game involvement in female college students.
AB  - PURPOSE: The purpose of this study was to test whether subjective evaluations of
      alcohol expectancies mediate the association between perceived drinking
      expectancies and participation in drinking games (DGs). Participation in DGs
      facilitates heavy drinking; therefore, we also examined the association between
      DG participation and alcohol-related problems. METHODS: This cross-sectional
      study included 187 female athletes from an all-women's college in the
      Northeastern United States. Respondents completed self-report questionnaires in
      small groups who reported on their alcohol use, drinking expectancies, and number
      of DGs played with their teammates during the semester. RESULTS: A mediation
      effect emerged for subjective evaluation of liquid courage expectancy but not for
      increased sociability and cognitive/behavioral impairment expectancies. Although
      perceived expectancies of cognitive/behavioral impairment were associated
      negatively with DG participation, positive subjective evaluations of this
      expectancy were related positively with DG participation. Finally, participation
      in DG was associated positively with alcohol-related problems. CONCLUSIONS:
      Findings are consistent with notions of social learning and utility theories and
      sheds light on the link between alcohol expectancies and participation in DGs
      among female student athletes. Results also highlight the health risks associated
      with DG involvement. Intervention programs aimed at decreasing the prevalence of
      DG participation might consider addressing students' perceptions about the
      desirability of liquid courage expectancies.

PMID- 15963915
TI  - Alcohol, tobacco and illicit substances in music videos: a content analysis of
      prevalence and genre.
AB  - Content analyses examined mention of alcohol, tobacco, and illicit substances in
      music videos (n = 359) broadcast in 2001, as well as genre and presence of humor.
      Findings indicated that references to illicit substances were more prevalent than
      tobacco in music videos. Humor was 2.5 times as likely to appear in videos
      containing references to substances than those without substances.

PMID- 15963916
TI  - GM-CSF gene-transduced tumor vaccines.
AB  - GVAX is a GM-CSF gene-transduced tumor vaccine. Expression of the GM-CSF gene
      within either autologous or allogeneic tumor cell populations has demonstrated
      evidence of immune stimulation in patients and evidence of antitumor activity
      particularly in prostate cancer and non-small-cell lung cancer. Results of
      preclinical studies justify clinical investigation. A summary of clinical results
      is presented.

PMID- 15963917
TI  - Cellular manipulation of human embryonic stem cells by TAT-PDX1 protein
      transduction.
AB  - Human embryonic stem cells (hESCs) are an in vitro model system for the study of
      human early development and a potential source for cell-based therapies. An
      efficient strategy for cellular manipulation of hESCs may be highly valuable for
      the analysis of gene function involved in human embryogenesis and the development
      of cell-based therapies via induced differentiation into particular cell types.
      However, plasmid transfection of hESCs has low efficiency and viral transduction
      may not be the method of choice for cell-based therapies due to genome
      integration. To overcome these limitations, we applied protein transduction
      technology that can transfer proteins into cells via direct penetration across
      the lipid bilayer. Here, we show that the FITC dye fused to the TAT protein
      transduction domain (PTD) was efficiently transferred into hESCs. In addition,
      the PDX1 transcription factor, which plays a central role in pancreatic
      development, was transferred into hESCs as a fusion form of TAT PTD. The
      transduced TAT-PDX1 activated its downstream target genes and induced insulin
      protein production in hESCs. These results demonstrate that protein transduction
      could be used in the cellular manipulation of hESCs and would provide a
      significant breakthrough for basic and therapeutic research in hESCs.

PMID- 15963918
TI  - High-resolution imaging of bone precursor cells within the intact bone marrow
      cavity of living mice.
AB  - Bone precursor cells (BPCs) play a critical role in bone maintenance and
      regeneration. Currently, no tool exists to study BPCs or other bone marrow cell
      types directly within their complex microenvironment. Here, we describe in vivo
      magnetic resonance imaging (MRI) of anatomical structures inside the medullary
      cavity of the mouse femur. We demonstrate that BPCs passively labeled with iron
      oxide-containing particles can be monitored by MRI within the intact bone marrow
      at an in-plane resolution of 43x25 microm. Anatomical detail provided by MRI is
      complemented by functional optical imaging of reporter gene expression. Single
      cell dual iron oxide-reporter gene labeling has potential for combined cell
      tracking and cell biology studies. In summary, we describe a versatile platform
      suitable for studying the biology of many bone marrow cell types in living bone.

PMID- 15963919
TI  - Real-time in vivo imaging of stem cells following transgenesis by transposition.
AB  - Previous studies have identified Sleeping Beauty transposons as efficient vectors
      for nonviral gene delivery in mammalian cells. However, studies demonstrating the
      usefulness of transposons as gene delivery vehicles into adult stem cells are
      lacking. Multipotent adult progenitor cells (MAPC) are nonhematopoietic stem
      cells with the capacity to form most, if not all, cell types of the body and as
      such hold great therapeutic potential. The whole-body biodistribution and
      persistence of MAPC are unknown, and such data would help direct clinical
      applications. We have nucleofected murine MAPC with two plasmid-based Sleeping
      Beauty transposons encoding the red fluorescent protein (DsRed2) and firefly
      luciferase. Transgenic euploid MAPC clones maintained their characteristic
      multilineage differentiation potential in vitro. DsRed2 and luciferase expression
      allowed for MAPC detection in vivo and in tissue sections. To confirm that
      transgenesis occurred by transposition into the genome of MAPC, we mapped
      Sleeping Beauty transposon integration sites in two MAPC clones using
      splinkerette PCR. This novel dual-reporter imaging approach based on the
      transgenesis of MAPC with Sleeping Beauty transposons sheds light on the homing
      patterns of MAPC and paves the way for quantification of MAPC engraftment in real
      time in vivo.

PMID- 15963920
TI  - Noninvasive imaging of ex vivo intracoronarily delivered nonviral therapeutic
      transgene expression in heart.
AB  - We developed a clinically applicable approach for noninvasive monitoring of
      reporter-therapeutic linked gene expression in the whole heart of large animals
      using PET imaging and further validated the efficacy and cardiac adverse effects
      of reporter-therapeutic linked gene transfer in a rabbit cervical heterotopic
      functional heart transplant model. Cationic liposome complexed with a vector
      containing a herpes simplex virus type 1 mutant thymidine kinase (HSV1-sr39tk) as
      the reporter gene and a recombinant human immunosuppressive cytokine, interleukin
      10 (hIL-10), as the therapeutic gene was ex vivo intracoronarily delivered into
      cardiac allografts before implantation. Long-term HSV1-sr39tk and hIL-10
      transgene and protein overexpression associated with myocardial PET reporter
      probe 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) accumulation was
      observed in the allografts. The expression of the HSV1-sr39tk gene was
      significantly correlated with the hIL-10 gene expression and the total myocardial
      [18F]FHBG accumulation quantified as a percentage of intravenously injected
      [18F]FHBG dose. A homogeneous distribution of [18F]FHBG accumulation was seen in
      the whole heart similar to the distribution of [18F]fluorodeoxyglucose, a PET
      glucose metabolism probe. The immunosuppressive therapeutic efficacy remained the
      same in allografts treated with reporter-therapeutic linked gene and therapeutic
      gene only. No cardiac adverse effect was found. Our results demonstrate for the
      first time that PET reporter-therapeutic linked gene imaging is applicable for
      noninvasively monitoring ex vivo intracoronarily delivered therapeutic transgene
      expression in the whole heart.

PMID- 15963921
TI  - Hepatocyte growth factor gene transfer to alveolar septa for effective
      suppression of lung fibrosis.
AB  - We examined therapeutic gene transfer of human hepatocyte growth factor (hHGF) to
      alveolar septa in mouse bleomycin-induced lung fibrosis using macroaggregated
      albumin-polyethylenimine complex (MAA-PEI). Intravenous administration of MAA-PEI
      along with 1 microg pCAG.hHGF to C57BL/6 mice increased the uptake of plasmids
      into alveolar capillary endothelial cells and epithelial cells, prolonged hHGF
      expression in the lung, and induced a level of hHGF expression equal to that seen
      with 10 microg of hHGF-expression plasmids alone. The exogenous source of hHGF
      gene expression increased the endogenous mouse HGF in the lungs and significantly
      decreased TNF-alpha, IL-6, and collagen synthesis after bleomycin injury. Because
      GFP-labeled bone marrow-derived stem cells after bleomycin injury were reduced in
      number by HGF, the primary mechanism of HGF is likely to be the prevention of
      apoptosis, as has been suggested by in vitro experiments. This novel HGF gene
      transfer method to alveolar septa with nonstimulatory MAA-PEI conjugates may have
      promising clinical applications.

PMID- 15963922
TI  - IFN-alpha gene therapy for woodchuck hepatitis with adeno-associated virus:
      differences in duration of gene expression and antiviral activity using
      intraportal or intramuscular routes.
AB  - Gene delivery of IFN-alpha to the liver may represent an interesting strategy to
      maximize its antiviral efficacy and reduce side effects. We used a recombinant
      adeno-associated virus (AAV) encoding woodchuck IFN-alpha (AAV-IFN) to treat
      animals with chronic woodchuck hepatitis virus infection. The vector was given by
      intraportal or intramuscular route. Long-term transgene expression was detected
      after intraportal administration of an AAV encoding luciferase. In contrast, in
      the majority of the animals that received AAV-IFN through the portal vein, the
      expression of IFN-alpha was transient (30-40 days) and was associated with a
      significant but transient decrease in viral load. One animal, in which hepatic
      production of IFN-alpha persisted at high levels, died because of bone marrow
      toxicity. The disappearance of IFN-alpha expression correlated with the
      disappearance of AAV genomes from the liver. Intramuscular administration of AAV
      IFN resulted in prolonged but fluctuating expression of the cytokine with no
      significant antiviral effect. In summary, this report shows that long-term
      expression of IFN-alpha in muscle is feasible but higher interferon levels might
      be needed to control viral replication. On the other hand, IFN-alpha gene
      delivery to the liver using an AAV vector induces a significant but transient
      antiviral effect in the woodchuck model.

PMID- 15963923
TI  - Selective survival of peripheral blood lymphocytes in children with HIV-1
      following delivery of an anti-HIV gene to bone marrow CD34(+) cells.
AB  - Two HIV-1-infected children on antiretroviral therapy were enrolled into a
      clinical study of retroviral-mediated transfer of a gene that inhibits
      replication of HIV-1, targeting bone marrow CD34+ hematopoietic stem/progenitor
      cells. Two retroviral vectors were used, one encoding a "humanized" dominant
      negative REV protein (huM10) that is a potent inhibitor of HIV-1 replication and
      one encoding a nontranslated marker gene (FX) to serve as an internal control for
      the level of gene marking. Peripheral blood mononuclear cells (PBMC) containing
      the huM10 gene or FX gene were detected by quantitative PCR at frequencies of
      approximately 1/10,000 in both subjects for the first 1-3 months following re
      infusion of the gene-transduced bone marrow, but then were at or below the limits
      of detection (<1/1,000,000) at most times over 2 years. In one patient, a
      reappearance of PBMC containing the huM10 gene, but not the FX gene, occurred
      concomitant with a rise in the HIV-1 viral load during a period of nonadherence
      to the antiretroviral regimen. Unique clones of gene-marked PBMC were detected by
      LAM-PCR during the time of elevated HIV-1 levels. These findings indicate that
      there was a selective survival advantage for PBMC containing the huM10 gene
      during the time of increased HIV-1 load.

PMID- 15963925
TI  - Increased hepatic transduction with reduced systemic dissemination and
      proinflammatory cytokines following hydrodynamic injection of helper-dependent
      adenoviral vectors.
AB  - Hydrodynamic injection of helper-dependent adenoviral vectors (HDAd) in mice
      results in increased hepatic transduction, reduced splenic and pulmonary
      transduction, and reduced levels of the proinflammatory cytokines IL-6 and IL-12
      compared to conventional injection. These results indicate that hepatic
      transduction by HDAd, at least alone, does not necessarily provoke a severe
      innate inflammatory response. Instead, they suggest that systemic vector
      dissemination may play a major role in the severity of the innate inflammatory
      response. These results further suggest that the safety and efficacy of HDAd
      mediated, liver-directed gene therapy may be improved if the vector could be
      preferentially, if not exclusively, targeted to liver.

PMID- 15963924
TI  - Intrapulmonary and intramyocardial gene transfer in rhesus monkeys (Macaca
      mulatta): safety and efficiency of HIV-1-derived lentiviral vectors for fetal
      gene delivery.
AB  - Fetal gene transfer was studied using intrapulmonary and intramyocardial transfer
      of SIN HIV-1-derived lentiviral vectors expressing EGFP in rhesus monkeys.
      Fetuses were monitored sonographically during gestation and tissue analyses
      performed at term or 3 months postnatal age. Animals remained healthy during the
      study period as evidenced by normal growth, development, hematology, clinical
      chemistry, echocardiography, and pulmonary function tests. Strong pulmonary
      fluorescence was observed postnatally after fetal intrapulmonary delivery of
      lenti-CMV, but not lenti-SP-C, and compared to nontransferred controls. High EGFP
      copy numbers were found by quantitative PCR with both vector constructs in lung
      lobes (<or=15%) and EGFP copies were also detected in the diaphragm, pericardium,
      and thorax. No differences were found in lung:body weight ratios, percentage lung
      parenchyma, or overall morphology when compared to controls. For intramyocardial
      gene delivery, strong transgene expression was found within the myocardium and
      pericardium, and high EGFP copy numbers were found by quantitative PCR (3-36%).
      EGFP was also detected in the aorta, thorax, and diaphragm. These studies
      indicate that postnatal heart and lung development and function were not altered
      after fetal intraorgan gene transfer and subsequent transgene expression
      prenatally and postnatally, and gene transfer was restricted to the thoracic
      cavity with intrapulmonary and intramyocardial lentiviral vector-mediated gene
      delivery.

PMID- 15963926
TI  - Combined genetic and chemical capsid modifications enable flexible and efficient
      de- and retargeting of adenovirus vectors.
AB  - Numerous attempts to target viral gene therapy vectors to specific cells have met
      with limited success. Here we describe a novel virus vector-targeting platform
      based on a unique combination of genetic and chemical vector particle
      modifications to overcome typical restrictions in virus vector targeting. We
      genetically introduced cysteines at solvent-exposed positions of the adenovirus
      capsid. The corresponding thiol groups were highly reactive, and we established
      procedures for controlled covalent coupling to them of protein and nonprotein
      ligands. After the coupling of transferrin, the particles were efficiently
      targeted to the transferrin receptor pathway. Depending on the chemistry used,
      ligands could be coupled under the formation of thioether or disulfide bonds, the
      latter allowing for separation of ligand and particle after cell entry in the
      endosome. Furthermore, this technology could be efficiently combined with vector
      shielding for true retargeting: after amino-PEGylation of the vector particles
      the genetically introduced thiols were still accessible for ligand coupling, and
      particles could be retargeted to the transferrin receptor. Since this platform is
      robust, can be scaled, is compatible with industrial standards, and can integrate
      chemically diverse molecules as ligands, it may be used for clinical gene therapy
      and, potentially, also for vaccination.

PMID- 15963927
TI  - Development of a transposon-based approach for identifying novel transgene
      insertion sites within the replicating adenovirus.
AB  - Therapeutic gene delivery from an oncolytic adenovirus (Ad) is one approach to
      enhancing the potency of Ad-based virotherapies for cancer. To identify
      therapeutic transgene insertion sites compatible with the replicating virus, a
      methodology that broadly scans the viral genome is needed. To address this we
      modified a transposon (Tn7)-based in vitro transposition system to take advantage
      of its nonprejudiced scanning ability to identify insertion sites compatible with
      viral replication. Using this system with a plasmid containing an E3-deleted Ad5,
      we identified several unique sites for promoter-based expression cassette
      insertions within the Ad genome. The transposon-based expression cassette is
      bounded by PmeI restriction endonuclease sites unique to the transposon, making
      expression cassette substitutions easy to perform. Additional expression
      cassettes containing different promoters and reporter genes were substituted into
      two of the newly identified transgene insertion sites. The results suggest that
      the ease and orientation of expression cassette substitution depend on both the
      insertion site location and the promoter and gene of the replacement expression
      cassette. These studies establish the transposon-based system as an efficient
      approach to scanning the Ad genome and identifying insertion sites compatible
      with viral replication and represents a powerful tool for the development of
      armed therapeutic viruses for cancer.

PMID- 15963928
TI  - Endogenously expressed multimeric self-cleaving hammerhead ribozymes ablate
      mutant collagen in cellulo.
AB  - Hammerhead ribozymes are small catalytic RNA molecules that can be targeted to
      any RNA molecule containing a putative cleavage site. We developed a vector
      (pCOLZ) that uses the COL1A1 promoter to drive expression of a self-cleaving
      multimeric ribozyme (M8Rz547) and its monomeric counterpart (Rz547). The
      ribozymes were stably coexpressed in MC3T3-E1 osteoblasts expressing a truncated
      COL1A1 target transcript. The multimeric ribozyme exhibited self-cleavage to
      derivative fragments, including monomers. Increased expression of ribozymes was
      found in cells expressing the multimeric ribozyme. A modest reduction of
      truncated target transcript and protein was seen in cells expressing the ribozyme
      monomer, while nearly complete ablation of target transcript and protein occurred
      in cells expressing the ribozyme multimer. A reversion to a more normal collagen
      phenotype, measured as an increase in fibril diameter and restored fibrillar
      architecture, and a decreased rate of collagen turnover were seen in cells
      expressing the ribozyme multimer.

PMID- 15963929
TI  - Prolonged transgene expression in murine salivary glands following non-primate
      lentiviral vector transduction.
AB  - Salivary glands are an accessible organ for gene therapy, enabling expression of
      recombinant proteins for both exocrine and endocrine secretion. Lentivirus-based
      vectors have many advantages for gene therapy, including their ability to infect
      nondividing cells and to stably integrate into the host genome, enabling long
      term transgene expression without eliciting an inflammatory immune response. In
      the present study, murine salivary glands were inoculated with feline
      immunodeficiency virus (FIV)-based lentiviral vectors expressing various reporter
      genes. Luciferase expression was observed as early as 24 h posttransduction,
      peaked at 17-21 days, and remained stable for more than 80 days. Staining with X
      gal suggested that mucous acinar cells were effectively transduced. FIV vector
      transduction with the secreted alkaline phosphatase gene increased serum levels
      in treated animals for up to 45 days, and the FIV vector harboring the interferon
      gamma (IFN-gamma) expression cassette induced an increase in IFN-gamma serum
      levels as well as in the supernatant of salivary gland explant cultures. These
      results demonstrate that the transduction of salivary glands with nonprimate
      lentiviral vectors may provide a novel and highly effective vehicle for long-term
      endocrine transgene expression.

PMID- 15963930
TI  - A microarray study to characterize the molecular mechanism of TIMP-3-mediated
      tumor rejection.
AB  - Glial cell invasion is a multistep cellular process that involves a complex
      system of tightly regulated proteases (matrix metalloproteinases; MMPs) and their
      endogenous inhibitors (tissue inhibitors of metalloproteinases; TIMPs) to mediate
      the degradation of the basement membrane and extracellular matrix. Tissue
      inhibitor of metalloproteinases-3 (TIMP-3) is a matrix-bound inhibitor of MMPs.
      In the present study, we have overexpressed the TIMP3 gene in human glioma cells
      with a herpes simplex virus type 1 amplicon-based vector. Oligonucleotide DNA
      arrays were employed to identify genes that were differentially modulated by the
      overexpression of TIMP-3. Consistent with the function of TIMP-3, genes
      associated with angiogenesis, growth factors, cytokines, death receptors, and
      substrates of the various MMPs were found to be up-regulated. Furthermore,
      caspases are important in the signaling pathway of cellular apoptosis, and the
      overexpression of TIMP-3 in glioma cells is tightly associated with the
      activation of caspases, including caspase-1, at both the mRNA level (P=0.0371)
      and the protein level. Moreover, the activation of an apoptotic pathway via the
      overexpression of TIMP-3 induced apoptosis of transduced human glioma cells in
      vitro and the growth inhibition of human glioma tumor xenografts in
      immunodeficient mice.

PMID- 15963931
TI  - Semliki forest virus vectors engineered to express higher IL-12 levels induce
      efficient elimination of murine colon adenocarcinomas.
AB  - To evaluate the use of alphavirus vectors for tumor treatment we have constructed
      and compared two Semliki Forest virus (SFV) vectors expressing different levels
      of IL-12. SFV-IL-12 expresses both IL-12 subunits from a single subgenomic
      promoter, while in SFV-enhIL-12 each IL-12 subunit is expressed from an
      independent subgenomic promoter fused to the SFV capsid translation enhancer.
      This latter strategy provided an eightfold increase of IL-12 expression. We chose
      the poorly immunogenic MC38 colon adenocarcinoma model to evaluate the
      therapeutic potential of SFV vectors. A single intratumoral injection of 10(8)
      viral particles of SFV-IL-12 or SFV-enh-IL-12 induced>or=80% complete tumor
      regressions with long-term tumor-free survival. However, lower doses of SFV-enhIL
      12 were more efficient than SFV-IL-12 in inducing antitumoral responses,
      indicating a positive correlation between the IL-12 expression level and the
      therapeutic effect. Moreover, repeated intratumoral injections of suboptimal
      doses of SFV-enhIL-12 increased the antitumoral response. In all cases SFV
      vectors were more efficient at eliminating tumors than a first-generation
      adenovirus vector expressing IL-12. In addition, the antitumoral effect of SFV
      vectors was only moderately affected by preimmunization of animals with high
      doses of SFV vectors. This antitumoral effect was produced, at least partially,
      by a potent CTL-mediated immune response.

PMID- 15963932
TI  - Beta-amino ester polymers facilitate in vivo DNA transfection and adjuvant
      plasmid DNA immunization.
AB  - Increased in vivo expression of intramuscularly delivered plasmid DNA will be
      essential for clinical success in gene therapy and plasmid DNA vaccination. We
      screened polymers from a library of beta-amino esters for their ability to
      augment transgene expression as measured by beta-galactosidase activity and
      cellular immune responses. Among the candidates identified in this screen,
      poly[(1,6-di(acryloxyethoxy)hexane)-co-(4-aminobutanol)] enhanced plasmid DNA
      transgene expression by sevenfold (P=0.0001) and its immunogenicity by 70%
      (P=0.03). We found that polymers with moderately hydrophobic backbones and
      terminal alcohol groups facilitated transfection most effectively in vivo. We
      also observed a log-linear correlation (R2=0.93) between peak cellular immune
      responses and transgene activity in all evaluated polymer-plasmid DNA
      formulations, clarifying the relationship between immunogenicity and the quantity
      of expressed antigen.

PMID- 15963933
TI  - Identification of factors that contribute to recombinant AAV2 particle
      aggregation and methods to prevent its occurrence during vector purification and
      formulation.
AB  - Aggregation of recombinant AAV2 results in reduced yield during purification and
      may have deleterious effects on vector transduction efficiency, biodistribution
      and immunogenicity following in vivo administration. Studies to elucidate the
      mechanism of vector aggregation and methods to prevent its occurrence are
      reported. In excipient screening studies, the sugars sorbitol, sucrose, mannitol,
      trehalose, or glycerol at concentrations of up to 5% (w/v), or surfactants Tween
      80 or Pluronic F68, did not prevent aggregation. Aggregation was prevented by the
      use of various salts at concentrations corresponding to solution ionic strengths
      of >200 mM. AAV2 vectors purified by double cesium chloride gradient
      centrifugation, cation-exchange chromatography, or combined chromatography and
      gradient centrifugation each demonstrated a similar requirement for ionic
      strength to prevent aggregation. AAV2 vectors concentrated to 6.7 x 10(13) vector
      genome (vg)/mL in neutral-buffered isotonic saline resulted in 59+/-6.0% recovery
      of nonaggregated material compared to 96+/-4.4% recovery in an isotonic
      formulation with elevated ionic strength. The latter showed no aggregation
      following storage or after 10 freeze-thaw cycles at -20 degrees C. AAV2 vectors
      stored for an extended period in an elevated ionic strength formulation retained
      a high infectivity titer (13 vg/infectious unit) and transduction efficiency.
      Nuclease digestion of purified AAV2 vectors reduced aggregation, implicating
      trace amounts of vector surface nucleic acids in interparticle binding.

PMID- 15963934
TI  - Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene
      promoter in HeLa cells.
AB  - Methylation of cytosines in CpG motifs is an important mechanism for epigenetic
      regulation of gene expression in mammalian cells. The initiating event(s) for de
      novo methylation in mammalian cells, particularly in cancer, is unknown. In
      plants, short RNAs homologous to DNA sequences are known to initiate de novo
      methylation. To investigate whether short hairpin RNAs (shRNAs) may also serve as
      initiators for de novo methylation in human cells we have expressed short hairpin
      RNAs complementary to the CpG island including the promoter and early transcribed
      regions of the human RASSF1A gene. RASSF1A encodes a putative tumor suppressor
      that is hypermethylated in a variety of human cancers, whereas in some human cell
      lines, such as HeLa, RASSF1A is unmethylated and transcriptionally active. We
      demonstrate that shRNAs complementary to the RASSF1A promoter or early
      transcribed regions can direct low levels of de novo DNA methylation and partial
      gene silencing in HeLa cells. In contrast, an shRNA harboring four central
      mismatches with the target cannot direct such methylation. The results presented
      suggest provocative potential mechanisms for transcriptional gene silencing via
      DNA methylation in cancer cells.

PMID- 15963935
TI  - Top-down contingent capture by color: evidence from RT distribution analyses in a
      manual choice reaction task.
AB  - According to the contingent capture hypothesis, observers can specify their
      control settings in advance of the target's presentation to quickly attend to
      relevant target colors. Two predictions were derived from this hypothesis and
      tested in a manual choice response task. First, contingent capture by color was
      expected: capture of spatial attention by a better-matching color stimulus should
      be stronger than capture by a less-matching color stimulus. Second, with the
      control settings specified in advance, the contingent capture by color should
      commence early after the stimulus onset and should be evident among fast correct
      responses in an RT distribution. Both predictions are shown to hold true in two
      experiments. Results are discussed in light of contrasting evidence for saccadic
      instead of manual responses.

PMID- 15963936
TI  - Acanthamoeba isolates belonging to T1, T2, T3, T4 but not T7 encyst in response
      to increased osmolarity and cysts do not bind to human corneal epithelial cells.
AB  - Acanthamoeba is an opportunistic protozoan that is widely distributed in the
      environment and can cause human infections. The life cycle of Acanthamoeba
      consists of an infective trophozoite form. However under harsh environmental
      conditions trophozoites differentiate into a double-walled, metabolically
      inactive and resistant cyst form. Research in Acanthamoeba has mostly focussed on
      the infective trophozoite form and its pathogenic mechanisms. In this study, we
      used Acanthamoeba isolates belonging to T1, T2, T3, T4, T7 genotypes and studied
      their cysts properties. We determined that food deprivation stimulates encystment
      in Acanthamoeba isolates belonging to T1, T2, T3, T4 and T7 genotypes in a sodium
      dodecyl sulfate (SDS)-resistant manner. In addition, increase in osmolarity
      triggered encystment in T1, T2, T3, T4 isolates (SDS-resistant) but T7 failed to
      encyst (SDS-labile). Adhesion assays revealed that Acanthamoeba cysts belonging
      to T1, T2, T3, T4, and T7 genotypes exhibited no and/or minimal binding (<5%) to
      the host cells. Fluorescein-labelled lectins showed that all Acanthamoeba
      isolates tested exhibited binding to concanavalin A, indicating the expression of
      mannosyl- and/or glucosyl-residues. Role of cysts in the transmission of
      infection is discussed further.

PMID- 15963937
TI  - Occult chorioretinal anastomosis in age-related macular degeneration: a
      prospective study by optical coherence tomography.
AB  - PURPOSE: To investigate macular optical coherence tomography (OCT) features in
      patients with chorioretinal anastomosis (CRA) and drusen, as well as their
      correlation with the Gass occult-CRA hypothesis. DESIGN: Prospective
      observational case series. METHODS: setting: Tertiary ophthalmic referral center.
      study population: All patients with biomicroscopic evidence of CRA and drusen
      consecutively evaluated between February 2003 and March 2004. observation
      procedures: Third-generation OCT evaluation and stereoscopic angiographic
      studies. main outcome measures: Macular morphologic features at baseline and at
      12 weeks. RESULTS: Twenty eyes with CRA and drusen were identified in 11
      patients, seven women (63.6%) and four men (36.4%) ranging in age from 69 to 82
      years (median, 79 years). Focal elevation of the retinal pigment epithelium was
      seen in eyes with stage 1 (pre-clinical) CRA. Small hyperreflective signals at
      the level of the elevated retinal pigment epithelium were seen in stage 2 CRA. In
      stage 3 CRA, a hyperreflective "mound" at the level of the elevated retinal
      pigment epithelium was seen in association with a thickened retina. In stage 4
      CRA sub-retinal pigment epithelium fluid accumulation was present, and complete
      disorganization of the macular region was observed in stage 5 CRA. Macular
      changes were observed in eight eyes (40%) at follow-up, with all but one CRA
      lesion progressing one stage. CONCLUSION: Morphologic features and changes
      demonstrated by OCT suggest that fibrovascular detachment of the retinal pigment
      epithelium followed by development of occult CRA are the initial events occurring
      in eyes with CRA in age-related macular degeneration. Our findings may support
      the evolutionary CRA staging system proposed by Gass.

PMID- 15963938
TI  - Synthesis and characterization of fluorescent ubiquitin derivatives as highly
      sensitive substrates for the deubiquitinating enzymes UCH-L3 and USP-2.
AB  - Deubiquitinating enzymes (DUBs) catalyze the removal of attached ubiquitin
      molecules from amino groups of target proteins. The large family of DUBs plays an
      important role in the regulation of the intracellular homeostasis of different
      proteins and influences therefore key events such as cell division, apoptosis,
      etc. The DUB family members UCH-L3 and USP2 are believed to inhibit the
      degradation of various tumor-growth-promoting proteins by removing the trigger
      for degradation. Inhibitors of these enzymes should therefore lead to enhanced
      degradation of oncoproteins and may thus stop tumor growth. To develop an
      enzymatic assay for the search of UCH-L3 and USP2 inhibitors, C-terminally
      labeled ubiquitin substrates were enzymatically synthesized. We have used the
      ubiquitin-activating enzyme E1 and one of the ubiquitin-conjugating enzymes E2 to
      attach a fluorescent lysine derivative to the C terminus of ubiquitin. Since only
      the epsilon-NH(2) group of the lysine derivatives was free and reactive, the
      conjugates closely mimic the isopeptide bond between the ubiquitin and the lysine
      side chains of the targeted proteins. Various substrates were synthesized by this
      approach and characterized enzymatically with the two DUBs. The variant
      consisting of the fusion protein between the large N-terminal NusA tag and the
      ubiquitin which was modified with alpha-NH(2)-tetramethylrhodamin-lysine, was
      found to give the highest dynamic range in a fluorescence polarization readout.
      Therefore we have chosen this substrate for the development of a miniaturized,
      fluorescence-polarization-based high-throughput screening assay.

PMID- 15963939
TI  - An oxygraphic method for determining kinetic properties and catalytic mechanism
      of aromatic amino acid hydroxylases.
AB  - We have developed a simple and versatile oxygraphic assay procedure that can be
      used for determination of kinetic constants and enzyme reaction mechanisms of
      wild-type and mutant aromatic amino acid hydroxylases. The oxygen concentration
      and rate of oxygen consumption were measured continuously throughout the enzyme
      reaction, while aliquots of the reaction mixture were removed at regular
      intervals for measurement of other substrates and products. Using (6R)
      tetrahydrobiopterin as electron donor in the phenylalanine hydroxylase (PAH)
      reaction, a stable stoichiometry of 1:1 was obtained between the amount of oxygen
      consumed and the tyrosine formation. In comparison, low and variable coupling
      efficiency values between oxygen consumption and tyrosine formation were found
      using the parent unsubstituted tetrahydropterin. The application of this assay
      procedure to study mechanisms of disease-associated mutations was also
      demonstrated. Thus, the phenylketonuria-associated PAH mutant R158Q had a
      coupling efficiency of about 80%, compared to the wild-type enzyme under similar
      conditions. Furthermore, the amount of H(2)O(2) produced in the reaction
      catalyzed by R158Q PAH was about four times higher than the amount produced by
      the wild-type PAH, demonstrating a possible pathogenetic mechanism of the mutant
      enzyme.

PMID- 15963940
TI  - Quantitative determination of intact glucosinolates in broccoli, broccoli
      sprouts, Brussels sprouts, and cauliflower by high-performance liquid
      chromatography-electrospray ionization-tandem mass spectrometry.
AB  - Many methods have been proposed to analyze glucosinolates, a class of
      phytochemicals whose breakdown products are thought to be responsible for an
      improvement in health; however, few are quantitative and many are time consuming.
      A selective and sensitive quantitative method for direct determination of intact
      glucosinolates was developed using liquid chromatography coupled to electrospray
      ionization tandem mass spectrometry with selected reaction monitoring detection.
      Detection limits for glucoiberin, sinigrin, progoitrin, glucoerucin, and
      glucotropaeolin were 1.75, 1.38, 1.36, 0.6, and 0.63 pmol, respectively.
      Intraassay precision of the method was within 10% for each compound. The method
      was successfully applied to quantify 10 individual glucosinolates in broccoli,
      broccoli sprouts, Brussels sprouts, and cauliflower. The advantage of the
      proposed method includes analysis of individual intact glucosinolates rather than
      the conversion to desulfoglucosinolates, an increased selectivity through the use
      of mass spectrometry, and a 10-fold improvement in detection sensitivity over
      conventionally used HPLC techniques.

PMID- 15963941
TI  - Binding of 10-N-nonyl acridine orange to cardiolipin-deficient yeast cells:
      implications for assay of cardiolipin.

PMID- 15963943
TI  - Effects of farnesol on the physical properties of DMPC membranes.
AB  - Farnesol interacts with membranes in a wide variety of biological contexts, yet
      our understanding of how it affects lipid bilayers is not yet complete. This
      study investigates how the 15-carbon isoprenoid, farnesol, influences the phase
      behaviour, lateral organization, and mechanical stability of dimyristol
      phosphatidylcholine (DMPC) model membranes. Differential scanning calorimetry
      (DSC) of multilamellar DMPC-farnesol mixtures (up to 26 mol% farnesol)
      demonstrates how this isoprenoid lowers and broadens the gel-fluid phase
      transition. A gel-fluid coexistence region becomes progressively more dominant
      with increasing farnesol concentration and at concentrations of and greater than
      10.8 mol%, an upper transition emerges at about 35 degrees C. Atomic force
      microscopy images of supported farnesol-DMPC bilayers containing 10 and 20 mol%
      farnesol provide structural evidence of gel-fluid coexistence around the main
      transition. Above this coexistence region, membranes exhibit homogeneous lateral
      organization but at temperatures below the main gel-fluid coexistence region,
      another form of phase coexistence is observed. The solid nature of the gel phase
      is confirmed using micropipette aspiration. The combined thermodynamic,
      structural, and mechanical data allow us to construct a phase diagram. Our
      results show that farnesol preferentially partitions into the fluid phase and
      induces phase coexistence in membranes below the main transition of the pure
      lipid.

PMID- 15963942
TI  - Fluorescent substrates for soluble epoxide hydrolase and application to
      inhibition studies.
AB  - Inhibition of the mammalian soluble epoxide hydrolase (sEH) is a promising new
      therapy in the treatment of disorders resulting from hypertension and vascular
      inflammation. A spectrophotometric assay (4-nitrophenyl-trans-2,3-epoxy-3
      phenylpropyl carbonate, NEPC) is currently used to screen libraries of chemicals;
      however this assay lacks the required sensitivity to differentiate the most
      potent inhibitors. A series of fluorescent alpha-cyanoester and alpha
      cyanocarbonate epoxides that produce a strong fluorescent signal on epoxide
      hydrolysis by both human and murine sEH were designed as potential substrates for
      an in vitro inhibition assay. The murine enzyme showed a broad range of
      specificities, whereas the human enzyme showed the highest specificity for
      cyano(6-methoxy-naphthalen-2-yl)methyl trans-[(3-phenyloxiran-2-yl)methyl]
      carbonate. An in vitro inhibition assay was developed using this substrate and
      recombinant enzyme. The utility of the fluorescent assay was confirmed by
      determining the IC(50) values for a series of known inhibitors. The new IC(50)
      values were compared with those determined by spectrophotometric NEPC and
      radioactive tDPPO assays. The fluorescent assay ranked these inhibitors on the
      basis of IC(50) values, whereas the NEPC assay did not. The ranking of inhibitor
      potency generally agreed with that determined using the tDPPO assay. These
      results show that the fluorescence-based assay is a valuable tool in the
      development of sEH inhibitors by revealing structure-activity relationships that
      previously were seen only by using the costly and labor-intensive radioactive
      tDPPO assay.

PMID- 15963944
TI  - Structure-dependent and receptor-independent increase in osmotic fragility of rat
      erythrocytes by short-chain fatty acids.
AB  - We examined short-chain fatty acids (SCFAs) with 1 (C1) to 5 (C5) carbon atoms
      for osmotic fragility (OF) in isolated red blood cells (RBCs) in rats. The RBCs
      were used as prototypical plasma membrane model. The dense packed RBC was
      incubated in a phosphate-NaCl buffer solution containing each SCFA at 0 to 100
      mM. The RBC suspensions were transferred into the OF test tubes containing NaCl
      from 0.2 to 0.9%. The hemoglobin concentration was determined and the EC50 in
      hemolysis was calculated. The OF in RBCs was dose-dependently increased by
      exposure to SCFAs, except for C1, with an increasing number of carbon atoms.
      Branched-chain fatty acids (isomers of C4 and C5) have a smaller effect on OF
      than straight-chain fatty acids (C4 and C5). The SCFA-induced increases in OF
      were not affected by pretreatment of RBCs with trypsin. The response of the RBC
      membrane to SCFAs depends on their concentration, carbon chain length and chain
      structure (straight or branched). The SCFAs probably disturb the lipid bilayer of
      the RBC membrane and result in a decrease in osmotic resistance. The plasma
      membrane in rat RBCs could respond to the structure of the SCFAs in detail by
      using the OF as an indicator.

PMID- 15963945
TI  - Suppression of hLRH-1 mediated by a DNA vector-based RNA interference results in
      cell cycle arrest and induction of apoptosis in hepatocellular carcinoma cell BEL
      7402.
AB  - RNA interference (RNAi) is the process by which double-stranded RNA directs
      sequence-specific degradation of mRNA. A DNA vector-based approach has been shown
      to be able to trigger RNA interference in mammalian cells successfully. LRH-1 is
      an orphan nuclear receptor predominantly expressed in tissues of endodermal
      origin, where it controls development and cholesterol homeostasis. In the present
      study, we demonstrated that the expression of hLRH-1 and cyclin E1 in BEL-7402
      cells could be suppressed by up to approximately 80% via DNA vector-based RNA
      interference. The suppression of hLRH-1 resulted in cell cycle arrest mediated by
      the down-regulation of cyclin E1. Induction of apoptosis and down-regulation of
      Gadd45beta were also shown in hLRH-1 knock down BEL-7402 cells. These results,
      together with the findings that Gadd45beta remained unchanged in cyclin E1 RNAi
      cells, suggested that the induction of apoptosis by knock down of hLRH-1 was
      closely related to the down-regulation of Gadd45beta.

PMID- 15963946
TI  - Transcriptional upregulation of DNA polymerase beta by TEIF.
AB  - The overexpression of DNA polymerase beta (beta-pol) has been identified in lots
      of human cancers, but the mechanism has seldom been investigated. Telomerase
      transcriptional element-interacting factor (TEIF) can bind to hTERT promoter,
      stimulating its transcription and telomerase activities. Here, we report that
      TEIF could also enhance the expression of beta-pol at transcription level. TEIF
      could specifically activate transcription of beta-pol promoter, but not that of
      DNA polymerase alpha or delta promoter. The responsible sequences for binding of
      TEIF were revealed as GC-rich elements dispersing from +19 to -29 nt of beta-pol
      promoter, which due to mutations caused decreasing in binding of TEIF and
      apparent losing of transactivation activity. The in vivo interaction between TEIF
      and beta-pol promoter was identified by chromatin immunoprecipitation assay.
      Besides, ectopic expression of TEIF in HeLa cells could upregulate both levels of
      endogenous beta-pol mRNA and protein, and consequently increases resistance to
      the oxidative stress of H2O2. The data may provide new clue to the elucidation of
      beta-pol overexpression in cancers and also a functional link between beta-pol
      and telomerase.

PMID- 15963947
TI  - Striking differences of LDL receptor-related protein 1B expression in mouse and
      human.
AB  - The low density lipoprotein (LDL) receptor-related protein 1B (LRP1B) is a member
      of the expanding LDL receptor family, and is closely related to LRP. It was
      discovered as a putative tumor suppressor, and is frequently inactivated in human
      malignant tissues. However, the expression pattern of LRP1B in normal human
      tissues was unclear. In the present study, we analyzed LRP1B expression in normal
      mouse and human tissues. By using RT-PCR, we found that, while mouse LRP1B
      expression is mostly restricted to the brain, human LRP1B expression is more
      widespread with highest expression levels detected in the brain, adrenal gland,
      salivary gland, and testis. Although mouse LRP1B expresses in the forms of both
      full-length receptor tail and an alternatively spliced form lacking a 33-amino
      acid insert, human LRP1B is expressed exclusively in the form of full-length
      receptor tail. Finally, we found that, unlike mouse LRP1B, human LRP1B is cleaved
      by furin. Taken together, these data demonstrate that there are striking
      differences between LRP1B expression in mouse and human tissues. The broader
      expression pattern of LRP1B in human tissues suggests that this putative tumor
      suppressor may play roles in several types of human cancer.

PMID- 15963948
TI  - The combination of TRAIL and luteolin enhances apoptosis in human cervical cancer
      HeLa cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the
      most promising candidates for cancer therapeutics. However, some tumor cells are
      resistant to TRAIL-induced apoptosis. Our previous studies have shown that
      luteolin, a naturally occurring flavonoid, induces the up-regulation of death
      receptor 5 (DR5), which is a receptor for TRAIL. Here, we show for the first time
      that luteolin synergistically acts with exogenous soluble recombinant human TRAIL
      to induce apoptosis in HeLa cells, but not in normal human peripheral blood
      mononuclear cells. The combined use of luteolin and TRAIL induced Bid cleavage
      and the activation of caspase-8. Also, human recombinant DR5/Fc chimera protein,
      caspase inhibitors, and DR5 siRNA efficiently reduced apoptosis induced by co
      treatment with luteolin and TRAIL. These results raise the possibility that this
      combined treatment with luteolin and TRAIL might be promising as a new therapy
      against cancer.

PMID- 15963949
TI  - Inhibitory effect of genistein on mouse colon cancer MC-26 cells involved TGF
      beta1/Smad pathway.
AB  - TGF-beta1/signaling has been shown to be associated with proapoptotic and
      antimitotic activities in epithelial tissues. Genistein, a major component of
      soybean isoflavone, has multiple functions resulting in anticancer proliferation.
      We herein showed that genistein dose-dependently increased TGF-beta1 mRNA
      expression in mouse colon cancer MC-26 cells. A mouse monoclonal anti-TGF-beta1
      neutralizing antibody partially, but not completely, blocked the growth
      inhibition by genistein. By using adenoviral vector, we demonstrated that Smad7
      overexpression attenuated genistein-induced growth inhibition and apoptosis as
      determined by MTT and apoptosis ELISA. Smad7 overexpression also inhibited
      upregulation of p21 and caspase-3 activity by geinistein. To further confirm
      inhibitory effect of genistein in MC-26 cells require TGF-beta1/Smad signaling,
      we employed Western blot and electrophoretic mobility shift assay to detect
      formation of Smad-DNA complexes and phosphorylation of Smad2 and Smad3,
      respectively. Data revealed that genistein induced an evident formation of Smad
      DNA complexes and phosphorylation of Smad2 and Smad3, indicating increased TGF
      beta1 signaling. Taken together, these findings first provided insights into
      possible molecular mechanisms of growth inhibition by genistein that required
      Smad signaling, which could aid in its evaluation for colon tumor prevention.

PMID- 15963950
TI  - A point mutation at phenylalanine 663 abolishes protein kinase C alpha's ability
      to translocate to the perinuclear region and activate phospholipase D1.
AB  - Previous research showed that protein kinase C alpha (PKC alpha) translocated to
      the perinuclear region and activated phospholipase D1, but the mechanism involved
      was not clear. Here, we provide evidence that Phe 663 (the 10th amino acid from C
      terminus) of PKC alpha is essential for its translocation. A point mutation
      (F663D) completely blocked PKC alpha's binding to and activation of phospholipase
      D1. Further studies showed that deletion of the C-terminal nine amino acids of
      PKC alpha did not alter its translocation to the perinuclear region but deletion
      of the C-terminal 10 amino acids and the F663D mutation abolished this
      translocation. The F663D mutant was found to be resistant to dephosphorylation,
      which might account for its inability to translocate to the perinuclear region
      and activate PLD1, since dephosphorylation of PKC alpha is required for its
      relocation from plasma membrane to the perinuclear region.

PMID- 15963951
TI  - Microarray analysis of tumour antigen expression in presentation acute myeloid
      leukaemia.
AB  - Acute myeloid leukaemia (AML) is a difficult to treat disease, especially for
      those patients who have no eligible haematopoietic stem cell (HSC) donor. One of
      the most promising treatment options for these patients is immunotherapy. To
      investigate the expression of known tumour antigens in AML, we analysed
      microarray data from 124 presentation AML patient samples and investigated the
      present/absent calls of 82 tumour-specific or -associated antigens. We found 11
      antigens which were expressed in AML patient samples but not normal donors. Nine
      of these were cancer-testis (CT) antigens, previously shown to be expressed in
      tumour cells and immunologically protected sites and at very low levels, if at
      all, in normal tissues. Expression was confirmed using real-time PCR. We have
      identified a number of CT antigens with expression in presentation AML samples
      but not normal donor samples, which may provide effective targets for future
      immunotherapy treatments early in disease.

PMID- 15963952
TI  - Proteomic analysis of human norepinephrine transporter complexes reveals
      associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins.
AB  - The norepinephrine transporter (NET) terminates noradrenergic signals by clearing
      released NE at synapses. NET regulation by receptors and intracellular signaling
      pathways is supported by a growing list of associated proteins including
      syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and
      Hic-5. In the present study, we sought evidence for additional partnerships by
      mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET
      (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our
      initial proteomic analyses reveal multiple peptides derived from hNET, peptides
      arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from
      14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co
      immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via
      a fusion pull-down approach, implicating specifically the hNET NH2-terminus for
      interactions. The transporter complexes described likely support mechanisms
      regulating transporter activity, localization, and trafficking.

PMID- 15963953
TI  - New "Birtoxin analogs" from Androctonus australis venom.
AB  - From the venom of the scorpion Androctonus australis, we have isolated a new
      bioactive polypeptide termed AaBTX-L1. When tested on the insect voltage-gated
      Na(+) channel (para) of the fruit fly, this toxin was able to induce a clear
      shift in activation (V(1/2)), resulting in the opening of the channel at more
      negative membrane potentials. Furthermore, AaBTX-L1 was totally devoid of
      toxicity when injected into mice intracerebroventricularly and did not compete
      with radiolabeled voltage-gated K(+) and Na(+) channel toxins in binding
      experiments on rat brain synaptosomes. Using its N-terminal amino acid sequence
      to design degenerate primers, several clones were amplified by PCR from the A.
      australis venom gland cDNA library. As a consequence, seven full oligonucleotide
      sequences encoding "long-chain" polypeptides with only three disulfide bridges
      have been cloned for the first time and are described here. Remarkably, they
      share high similarity with the anti-insect toxin Birtoxin from Parabuthus
      transvaalicus.

PMID- 15963954
TI  - Amphiphilic pyridinium salts block TNF alpha/NF kappa B signaling and
      constitutive hypersecretion of interleukin-8 (IL-8) from cystic fibrosis lung
      epithelial cells.
AB  - Cystic fibrosis (CF) is a common, lethal genetic disease, which is due to
      mutations in the CFTR gene. The CF lung expresses a profoundly proinflammatory
      phenotype, due to constitutive hypersecretion of IL-8 from epithelial cells
      lining the airways. In a systematic search for candidate drugs that might be used
      therapeutically to suppress IL-8 secretion from these cells, we have identified a
      potent and efficacious series of amphiphilic pyridinium salts. The most potent of
      these salts is MRS2481, an (R)-1-phenylpropionic acid ester, with an IC50 of ca.
      1microM. We have synthesized 21 analogues of MRS2481, which have proven
      sufficient to develop a preliminary structure-activity relationship (SAR). For
      optimal activity, we have found that the ester must be connected to the
      pyridinium derivative by an eight-carbon chain. An optical isomer of the lead
      compound, containing an (S)-1-phenylpropionic acid ester, has been found to be a
      much less active. The mechanism of action of MRS2481 appears to involve
      inhibition of signaling of the NF(kappa)B and AP-1 transcription factors to the
      IL-8 promoter. MRS2481 is a potent inhibitor of TNFalpha-induced phosphorylation
      and proteosomal destruction of I(kappa)B(alpha). Inasmuch as I(kappa)B(alpha) is
      the principal inhibitor of the NF(kappa)B signaling pathway, preservation of
      intact I(kappa)B(alpha) would serve to keep the IL-8 promoter silent. We also
      find that MRS2481 blocks TNF(alpha)-activated phosphorylation of JNK, the c-JUN
      kinase. The IL-8 promoter is also activated by an AP-1 site, which requires a
      phospho-c-JUN/c-FOS dimer for activity. We therefore interpret these data to
      suggest that the mechanism of MRS2481 action is to inhibit both NF(kappa)B and AP
      1 signaling on the IL-8 promoter. Given the medicinally promising properties of
      water-solubility, potency in the low muM concentration range, and high efficacy,
      we anticipate that MRS2481, or a further optimized derivative, may find an
      important place in the armamentarium of pharmaceutical strategies yet to be
      arrayed against the inflammatory phenotype of the CF lung.

PMID- 15963956
TI  - Role of mitogen-activated protein kinases during recovery from head-shake
      response habituation in rats.
AB  - Habituation is defined as a decrease in responsiveness to a repeatedly presented
      stimulus. The head-shake response (HSR) consists of a rapid twisting of the head
      about the front-to-rear axis elicited by a stream of air to the ear. This
      response demonstrates several fundamental properties of habituation including
      sensitivity to the frequency and intensity of stimulation, and spontaneous
      recovery. Despite an abundance of behavioral data on the HSR, relatively little
      is known about its physiological mechanism(s). To address this issue, changes in
      mitogen-activated protein kinases (MAPK) were assessed 5 min and 2, 6, and 24 h
      following the habituation of the HSR. Three cascades of MAPK activity were
      measured in the cerebellum and hippocampal, prefrontal, and piriform cortices,
      including extracellular-response kinase (ERK), p-38 kinase (p-38), and stress
      activated protein kinase (SAPK). Significant activation of p-38 and SAPK was
      observed in all four brain structures, accompanied by modest changes in ERK
      activity. Recovery of the HSR was characterized by decreasing MAPK activation
      with control levels re-established 24 h after habituation. The present results
      suggest that MAPK activation mediates recovery from habituation; however, these
      findings may also support alternative interpretations such that MAPK activation
      reflects the encoding of spatial cues associated with the testing environment
      and/or are due to stress induced by the habituation protocol.

PMID- 15963955
TI  - Interactions of peroxynitrite with uric acid in the presence of ascorbate and
      thiols: implications for uncoupling endothelial nitric oxide synthase.
AB  - It has been suggested that uric acid acts as a peroxynitrite scavenger although
      it may also stimulate lipid peroxidation. To gain insight into how uric acid may
      act as an antioxidant, we used electron spin resonance to study the reaction of
      uric acid and plasma antioxidants with ONOO-. Peroxynitrite reacted with typical
      plasma concentrations of urate 16-fold faster than with ascorbate and 3-fold
      faster than cysteine. Xanthine but not other purine-analogs also reacted with
      peroxynitrite. The reaction between ONOO- and urate produced a carbon-centered
      free radical, which was inhibited by either ascorbate or cysteine. Moreover,
      scavenging of ONOO- by urate was significantly increased in the presence of
      ascorbate and cysteine. An important effect of ONOO- is oxidation of
      tetrahydrobiopterin, leading to uncoupling of nitric oxide synthase. The
      protection of eNOS function by urate, ascorbate and thiols in ONOO(-)-treated
      bovine aortic endothelial cells (BAECs) was, therefore, investigated by measuring
      superoxide and NO using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5
      tetramethyl-pyrrolidine (CMH) and the NO-spin trap Fe[DETC]2. Peroxynitrite
      increased superoxide and decreased NO production by eNOS indicating eNOS
      uncoupling. Urate partially prevented this effect of ONOO- while treatment of
      BAECs with the combination of either urate with ascorbate or urate with cysteine
      completely prevented eNOS uncoupling caused by ONOO-. We conclude that the
      reducing and acidic properties of urate are important in effective scavenging of
      peroxynitrite and that cysteine and ascorbate markedly augment urate's
      antioxidant effect by reducing urate-derived radicals.

PMID- 15963957
TI  - Glycinergic and GABAergic synaptic transmission are differentially affected by
      gephyrin in spinal neurons.
AB  - In the present study, we have examined the physiological properties of synaptic
      currents mediated by GlyRs and GABAARs after culturing spinal neurons with a
      gephyrin antisense oligonucleotide. Application of gephyrin antisense, but not
      the sense, reduced the glycinergic mIPSC amplitude ( approximately 50%) and
      frequency ( approximately 85%), indicating the importance of gephyrin for GlyR
      anchoring at postsynaptic sites. On the other hand, the glycine-evoked current
      amplitude was unchanged indicating that functional GlyRs were still located in
      the extrasynaptic membrane. The analysis of the GABAergic transmission in the
      same neurons revealed approximately 70% reduction in the frequency of the
      GABAergic mIPSCs, without changes in the amplitude. Interestingly, the modulation
      of remaining GABAAR-mediated synaptic events by zinc and diazepam was
      significantly altered by the antisense. These results indicate that gephyrin is
      required for the membrane insertion/stabilization of the GABAAR gamma2 subunit as
      well as for its subsequent localization in the postsynaptic membrane.

PMID- 15963958
TI  - Cholinergic stimulation in the lateral septal area activates anterior
      hypothalamic area neurons via excitatory amino acid receptors in rats.
AB  - We have previously reported that some neurons in the anterior hypothalamic area
      (AHA) are tonically activated by endogenous angiotensins in rats and that
      activities of these AHA angiotensin II-sensitive neurons are enhanced in
      spontaneously hypertensive rats. It is suggested that there exist neuronal
      projections from the lateral septal area (LSV) to the AHA in rats. In this study,
      we examined whether neurons in the LSV are involved in activation of AHA
      angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and
      artificially ventilated. Extracellular potentials were recorded from single
      neurons in the AHA. Microinjection of carbachol into the LSV caused an increase
      in firing rate of AHA angiotensin II-sensitive neurons. The carbachol-induced
      increase of firing rate of AHA angiotensin II-sensitive neurons was inhibited by
      pressure application of the excitatory amino acid receptor antagonist kynurenate
      but not by the AT1 receptor antagonist losartan onto the same neurons.
      Microinjection of carbachol into the LSV also increased the firing rate of AHA
      ACh-sensitive neurons, and the carbachol-induced increase of firing rate of ACh
      sensitive neurons was again abolished by pressure application of kynurenate but
      not by the muscarinic receptor antagonist scopolamine onto the same neurons.
      Microinjection of the muscarinic receptor antagonist 4-DAMP into the LSV did not
      affect the firing rate of AHA angiotensin II-sensitive neurons. These findings
      indicate that neurons in the LSV are involved in activation of AHA angiotensin II
      sensitive neurons. It seems likely that the carbachol-induced activation of AHA
      angiotensin II-sensitive neurons is mainly mediated via excitatory amino acid
      receptors at AHA neurons.

PMID- 15963959
TI  - Nonaqueous synthesis of a selectively modified, highly anionic sulfopropyl ether
      derivative of cyclomaltoheptaose (beta-cyclodextrin) in the presence of 18-crown
      6.
AB  - A highly anionic cyclomaltooligosaccharide (cyclodextrin, CD) derivative
      containing sulfopropyl functional groups on the primary face of the CD was
      synthesized. Heptakis(2,3-di-O-methyl)cyclomaltoheptaose [heptakis(2,3-di-O
      methyl)-beta-cyclodextrin] was reacted with 1,3-propane sultone and potassium
      hydride (KH) in anhydrous tetrahydrofuran in the presence of 18-crown-6 to yield
      highly substituted potassium heptakis(2,3-di-O-methyl-6-O
      sulfopropyl)cyclomaltoheptaose [heptakis(KSPDM)-beta-CD] with an average degree
      of substitution (DSCE) of 6.9 as determined by inverse detection capillary
      electrophoresis (CE). The principal species in the product is the fully
      substituted heptakis(KSPDM)-beta-CD. Complete NMR assignments of the hydrogen and
      carbon atoms are made using a combination of gCOSY and gHSQC. In the absence of
      18-crown-6, the reaction generates a mixture of multiply charged derivatives with
      average DSCE of 4.1. The possible roles of the crown ether in the reaction are
      discussed. The ROESY NMR spectrum of the inclusion complex that forms between
      heptakis(KSPDM)-beta-CD and 2-naphthoic acid in D2O reveals that 2-naphthoic acid
      inserts with the carboxyl group toward the derivatized primary rim of the
      cyclodextrin.

PMID- 15963961
TI  - Determination of the degree of deacetylation of chitin and chitosan by X-ray
      powder diffraction.
AB  - A new method to determine the degree of deacetylation (DD) of alpha-chitin and
      chitosan in the range of 17-94% DD using X-ray powder diffraction (XRD) is
      proposed. The results were calibrated using (1)H NMR spectroscopy for chitosan
      and FTIR for chitin, in comparison with the potentiometric titration method. The
      results showed a good linear correlation between the CrI020 from XRD and the
      calibrated DD value. This method is found to be simple, rapid and nondestructive
      to the sample.

PMID- 15963960
TI  - Carbohydrate, glycolipid, and lipid components from the photobiont (Scytonema
      sp.) of the lichen, Dictyomema glabratum.
AB  - The photobiont of the lichen, Dictyonema glabratum (Scytonema sp.), was isolated
      and cultivated in a soil-extract medium and submitted to chemical analysis.
      Successive extractions with CHCl3-MeOH, aqueous MeOH, and H2O gave rise to
      solutions of lipids (25%), low-molecular-weight carbohydrates (22%), and
      polysaccharides (4%), respectively. TLC of the lipid extract showed the presence
      of glycolipids, which were further purified and examined by NMR spectroscopy and
      GC-MS. Monogalactosyldiacylglycerol (1%), digalactosyldiacylglycerol (0.8%),
      trigalactosyldiacylglycerol (0.4%), and sulfoquinovosyldiacylglycerol (0.5%) were
      identified. The most abundant fatty acid ester in each fraction was palmitic
      (C16:0), but a great variation of the ester composition from one to another was
      found. Others present were those of C12:0, C14:0, C15:0, C16:1, C17:0, C18:0,
      C18:1, C18:2, C18:3, C22:0, C22:2, and C24:0. The lipid extract was also
      subjected to acid methanolysis, which gave rise to dodecane, 2-Me-heptadecane,
      2,6-Me2-octadecane, and 8-Me-octadecane, methyl esters of C14:0, C15:0, C16:0,
      C16:1, C17:0, C18:0, C18:1, C18:2, C20:0, and C24:0 fatty acids, and the dimethyl
      ester of decanedioic acid. The polysaccharide had mainly Glc, Gal, and Man, with
      small amounts of 3-O-methylrhamnose and 2-O-methylxylose, both found in plants,
      and unexpectedly, some of the units were beta-galactofuranose, typical of fungal,
      but not cyanobacterial polysaccharides. The low-molecular-weight carbohydrates
      showed mannose as the main free reducing sugar, which differs from Nostoc sp. and
      Trebouxia sp. photobionts.

PMID- 15963962
TI  - An alternative high yielding and highly stereoselective method for preparing an
      alpha-Neu5NAc-(2,6)-D-GalN3 building block suitable for further glycosylation.
AB  - This paper deals with new approaches to alpha-Neu5NAc-(2,6)-D-GalN3 building
      blocks, suitable as glycosylation donors. The major improvement, by comparison
      with the results of the literature, lies in the glycosylation step of a new d
      galactosamine acceptor (tert-butyldimethylsilyl 3-O-acetyl-2-azido-2-deoxy-beta-D
      galactopyranoside) with O-methyl-S-[methyl(5-acetamido-4,7,8,9-tetra-O-acetyl-3,5
      dideoxy-D-glycero-alpha-D-galacto-non-2-ulopyranosyl)onate] dithiocarbonate as
      the N-acetylneuraminic acid donor. The reaction affords the expected disaccharide
      in high yield (85%) and a complete alpha-Neu5NAc stereoselectivity. A subsequent
      oxidation step, eliminating the glycal by-product allows an easier purification.
      Afterwards, the tert-butyldimethylsilyl disaccharide can be transformed into a
      donor, after cleavage of the anomeric group in smooth conditions.

PMID- 15963963
TI  - Major O-glycans from the nest of Vespula germanica contain phospho-ethanolamine.
AB  - We describe here the structural deciphering of four wasp O-glycans. Following
      purification of a mixture of glycoproteins from nests of the common wasp Vespula
      germanica L. (Hymenoptera), their substituting O-glycans were liberated by
      reducing beta-elimination and characterised using a combination of high
      resolution NMR and mass spectrometry analyses. Besides ubiquitously found in the
      insect cells GalNAc-ol and Gal(beta1-3)GalNAc-ol compounds, two novel O-glycans
      carrying a 2-aminoethyl phosphate group were described for the first time here.
      We suggest that they present the following structures: Etn-P-(O-->6)-GalNAc-ol
      and Etn-P-(O-->6)-[Gal(beta1-3)]GalNAc-ol. In conjunction with previous studies,
      these results suggest that a 2-aminoethyl phosphate group may act as an
      alternative to sialic acid for conferring charges to glycoproteins.

PMID- 15963964
TI  - Oligosaccharide analyses of glycopeptides of horseradish peroxidase by thermal
      assisted partial acid hydrolysis and mass spectrometry.
AB  - Thermal-assisted partial acid hydrolysis of the carbohydrate moieties of N
      glycosylated peptides of horseradish peroxidase (HRP) is used to generate
      oligosaccharide cleavage ladders. These ladders allow direct reading of
      components of the oligosaccharides by mass spectrometry. Acid hydrolysis
      performed with 1.4, 3.1, 4.5, or 6.7M trifluoroacetic acid at 37, 65, or 95
      degrees C for 30min to 24h hydrolyzed mainly the oligosaccharide units of
      glycopeptides with least peptide bond or amino acid side chain hydrolysis.
      Tryptic N-glycosylated peptides from HRP with molecular weights of 2533, 2612,
      3355, 3673, and 5647Da were used as test systems in these experiments. Data
      showed that the most labile group of oligosaccharides is the fucose (Fuc) and the
      majority of the end cleavage products are peptides with one or no N
      acetylglucosamine (GlcNAc) residue linked to Asparagine (Asn). Additionally, the
      data agree with previous reports that glycopeptides 3355 and 3673Da carry an
      oligosaccharide (Xyl)Man3(Fuc)GlcNAc2, glycopeptide 5647Da carries two
      oligosaccharides (Xyl)Man3(Fuc)GlcNAc2, and glycopeptides 2612 and 2533Da carry
      (Xyl)Man3GlcNAc2 and (Fuc)GlcNAc, respectively. However, the glycosylation site
      of the 2612Da peptide at Asn286 is partially occupied. This method is
      particularly useful in identifying glycopeptides and obtaining monosaccharide
      compositions of glycopeptides.

PMID- 15963965
TI  - How viral infections affect the autoimmune process leading to type 1 diabetes.
AB  - Despite a large body of evidence describing associations between viruses and the
      development of type 1 diabetes (T1D) in genetically prone individuals, clearly
      defining causative infectious agents has not been successful. A likely
      explanation is that the link between infections and autoimmunity is more
      multifaceted than we initially assumed. Viral footprints might be hard to detect
      systemically or in the target organ once autoimmunity has been initiated, and
      several infections might have to act in concert to precipitate clinical
      autoimmunity. Furthermore, cells cross-reactive between viral and self-antigens
      might express low avidity T cell receptors and only be present transiently in the
      blood of affected individuals. In addition, there are two new observations from
      animal models that we should take into account at this point: first, viral
      infections alone might not be able to induce disease in the absence of other
      inflammatory factors (supporting the "fertile field hypothesis" [M.G. von Herrath
      et al., Microorganisms and autoimmunity: making the barren field fertile? Nat.
      Rev. Microbiol. 1 (2003) 151-157, ]). Second, increasing evidence indicates that
      viruses can play a role in preventing rather than enhancing T1D development
      (supporting the "hygiene hypothesis" [J.F. Bach, Protective role of infections
      and vaccinations on autoimmune diseases. J. Autoimmun. 16 (2001) 347-353]). In
      this article we will present an overview of the early events and requirements
      that could account for T1D predisposition and development, and explain how these
      can be modulated by viral infections. Focusing on coxsackie B and lymphocytic
      choriomeningitis virus infections, we will discuss new data that can hopefully
      help us understand how virus-induced inflammation can positively or negatively
      affect the clinical outcome of islet-autoimmunity and T1D.

PMID- 15963966
TI  - Six questions about the hygiene hypothesis.
AB  - According to the hygiene hypothesis, the increased incidence of allergic and
      autoimmune diseases in developed countries is explained by the decrease in
      infections. Several questions remain unsettled, concerning notably the nature of
      protective infections, the mechanisms of protection, the spectrum of diseases
      concerned by the hypothesis, the difference between triggering and protective
      infections and lastly the strategies which could be devised to mimic the effect
      of infections.

PMID- 15963967
TI  - Predominance of Th2 response in human abdominal aortic aneurysm: mistaken
      identity for IL-4-producing NK and NKT cells?
AB  - Abdominal aortic aneurysm (AAA) is a complex remodeling process that involves
      both synthesis and degradation of extracellular matrix proteins in the aortic
      wall, leading to decreased tensile strength, progressive dilation and eventual
      rupture. Chronic inflammation, increased local production of elastin-degrading
      proteases by inflammatory cells and destruction of medial elastic lamellae play
      important roles in aneurysm progression. Neovascularization in all layers of the
      arterial wall is prominent and angiogenesis can facilitate chronic inflammation.
      It is still unclear what initiates aneurysmal dilation and what determines its
      progression. The complex nature of the process has defied elucidation. Apart from
      macrophages, the predominant immune cell infiltrates reported so far are CD3(+)T
      cells that express CD4 and CD8. Infiltrates of type 2 Th cells and their
      production of IL-4 and IL-5 have been implicated in AAA development. However, NKT
      and NK cells have a Th0 cytokine profile and can also produce type 2 as well as
      type 1 (IL-2 and IFNgamma) cytokines. We have demonstrated the presence of NK and
      NKT cells in AAA tissue. With their growing importance in autoimmunity and
      transplantation, they may play a role in AAA development. Therefore, there is a
      need to use a combination of T and NK markers to fully characterize both innate
      and adaptive lymphoid cell subsets in local inflammatory infiltrates in order to
      elucidate their roles in AAA progression.

PMID- 15963968
TI  - Retrospective diagnosis of glycogen storage disease type II by use of a newborn
      screening card.

PMID- 15963969
TI  - Reference interval determination for N-terminal-B-type natriuretic peptide (NT
      proBNP): a study in blood donors.
AB  - We assessed reference values in a group of apparently healthy blood donors. A
      total of 1980 blood donors was recruited and tested for the presence of NT-proBNP
      using a newly developed electrochemiluminescence immunoassay (ECLIA) method. NT
      proBNP clustered in all blood donors below the age of 50 years and an upper limit
      of normal (ULN) was found to be 84 pg/ml for males and 146 pg/ml for females.
      Mean NT-proBNP values increased with increasing age which was due to an
      increasing number of individuals exceeding the ULN. Age- and gender-appropriate
      NT-proBNP levels decreased with increasing hemoglobin levels. Hemoglobin but not
      creatinine levels influenced the NT-proBNP concentration in this cohort. The
      upper limit of normal can be used in clinical studies to further assess groups of
      diseased individuals to define clinical cutoffs.

PMID- 15963970
TI  - Evaluation of plasma ammonia levels in patients with acute liver failure and
      chronic liver disease and its correlation with the severity of hepatic
      encephalopathy and clinical features of raised intracranial tension.
AB  - OBJECTIVES: The present study was designed to (a) evaluate and compare plasma
      ammonia levels (PAL) in patients with acute liver failure (ALF) and chronic liver
      disease (CLD) with or without hepatic encephalopathy (HE); (b) correlate the
      severity of HE with PAL; and (c) correlate PAL with clinical features of raised
      intracranial tension in ALF. DESIGN AND METHODS: A total of 40 patients,
      comprised of 20 patients with ALF (Group A) and 20 patients with CLD (Group B,
      which was comprised of 8 patients with HE (subgroup B1) and 12 patients without
      HE (subgroup B2)), were studied. PAL was estimated using an enzymatic UV-method
      (RANDOX). The clinical and biochemical profile of all the patients was recorded.
      Correlation between the grade of HE and PAL was derived using Pearson's
      correlation coefficient. The mean PAL of ALF patients with and without raised
      intracranial tension was compared using the standard error of difference between
      the two means. RESULTS: The mean PAL (micromol/L) +/- SD was as follows: Group A:
      172.1 +/- 52.55, subgroup B1: 58.75 +/- 29.38, subgroup B2: 42.17 +/- 18.19
      (normal levels = 10-47 micromol/L). All patients with ALF showed PAL more than
      the upper limit of the normal range, and there was good correlation between the
      severity of HE and PAL [r = 0.91 at P < 0.05]. In subgroup B1 (CLD with HE), 3/8
      patients (37.5%), and in subgroup B2 (CLD with HE), 4/12 patients (33.3%)
      patients had PAL more than the upper limit of normal range. Within Group A, 14
      patients had clinical features of raised intracranial tension/cerebral edema, and
      the mean PAL of these patients (188.21 +/- 49.15 micromol/L) was significantly
      higher than those who did not have features of raised intracranial tension (134.5
      +/- 42.36 micromol/L) (SE of difference between two means). CONCLUSIONS: Raised
      PAL appears to be an important laboratory abnormality seen in patients with ALF,
      and there seems to be a significant correlation between the severity of
      encephalopathy and PAL in these patients. However, among patients with CLD, the
      proportion of patients with PAL more than the upper limit of normal range is not
      significantly different between those with or without HE. Our study also suggests
      that high PAL in ALF patients appears to correlate with clinical features of
      cerebral edema and raised intracranial tension.

PMID- 15963971
TI  - Cu/Zn superoxide dismutase plasma levels as a new useful clinical biomarker of
      oxidative stress in patients with end-stage renal disease.
AB  - OBJECTIVES: We wanted to study the imbalance between antioxidant and oxidant
      generating systems resulting in oxidative stress (SOX) in end-stage renal disease
      (ESRD). We suggest that the plasma levels of Cu/Zn superoxide dismutase (Cu/Zn
      SOD) may be a new, sensitive marker of SOX in this population. DESIGN AND
      METHODS: We measured the levels of Cu/Zn SOD and the traditional SOX markers
      malondialdehyde (MDA), total peroxide, and autoantibodies against oxidized LDL
      (OxLDL-Ab) in the plasma of 132 uremic patients. In addition, circulating enzyme
      levels were analyzed in relation to the inflammation and presence of diabetes
      mellitus (DM). RESULTS: Cu/Zn SOD levels were significantly higher in chronic
      renal failure (CRF) patients (P < 0.05), and in both dialyzed groups (both P <
      0.001) than in controls, and were positively correlated with MDA, creatinine
      (both P < 0.001) and OxLDL-Ab (P < 0.01) in the whole uremic group. CONCLUSIONS:
      The plasma levels of Cu/Zn SOD may be a simple, sensitive marker of SOX in ESRD,
      independent from DM and inflammation.

PMID- 15963972
TI  - Determinants of trophoblast lineage and cell subtype specification in the mouse
      placenta.
AB  - Cells of the trophoblast lineage make up the epithelial compartment of the
      placenta, and their rapid development is essential for the establishment and
      maintenance of pregnancy. A diverse array of specialized trophoblast subtypes
      form throughout gestation and are responsible for mediating implantation, as well
      as promotion of blood to the implantation site, changes in maternal physiology,
      and nutrient and gas exchange between the fetal and maternal blood supplies.
      Within the last decade, targeted mutations in mice and the study of trophoblast
      stem cells in vitro have contributed greatly to our understanding of trophoblast
      lineage development. Here, we review recent insights into the molecular pathways
      regulating trophoblast lineage segregation, stem cell maintenance, and subtype
      differentiation.

PMID- 15963973
TI  - Development of porcine embryos in vivo and in vitro; evidence for embryo 'cross
      talk' in vitro.
AB  - The in vitro development of zygotes of domestic species to the blastocyst stage
      is facilitated by culture in groups, suggesting a role for autocrine/paracrine
      factors. A novel method was used to investigate the potential role of such
      factors using in-vitro-produced and in-vivo-derived porcine embryos. The
      development of individual zygotes to the blastocyst stage was optimal when they
      were cultured 81-160 mum apart. As the distance between the embryos was
      increased, blastocyst rates declined significantly, reaching zero beyond 640 mum.
      Blastocyst volume and cell number (both inner cell mass and trophectoderm) were
      also increased when the distance apart was between 81 and 160 mum. Culturing
      embryos in groups at different stages of development suggested that group culture
      confers a greater advantage to development after the activation of the genome.
      Group culture of in-vivo-derived embryos showed a weak distance effect. The
      results suggest a role for as yet unknown diffusible paracrine/autocrine factors
      released by early porcine embryos in promoting the growth of neighbouring embryos
      in vitro. This advantage is observed to a lesser extent by in-vivo-derived
      zygotes which are likely to have been better conditioned for development in vitro
      by being conceived in the female reproductive tract.

PMID- 15963974
TI  - Expression of a secreted form of Dally, a Drosophila glypican, induces overgrowth
      phenotype by affecting action range of Hedgehog.
AB  - Glypicans, a family of heparan sulfate proteoglycans attached to the cell surface
      via a glycosylphosphatidylinositol (GPI)-anchor, play essential roles in
      morphogen signaling and distributions. A Drosophila glypican, Dally, regulates
      the gradient formation of Decapentaplegic (Dpp) in the developing wing. To gain
      insights into the function of glypicans in morphogen signaling, we examined the
      activities of two mutant forms of Dally: a transmembrane form (TM-Dally) and a
      secreted form (Sec-Dally). Misexpression of tm-dally in the wing disc had a
      similar yet weaker effect in enhancing Dpp signaling compared to that of wild
      type dally. In contrast, Sec-Dally shows a weak dominant negative activity on Dpp
      signal transduction. Furthermore, sec-dally expression led to patterning defects
      as well as a substantial overgrowth of tissues and animals through the expansion
      of the action range of Hh. These findings support the recently proposed model
      that secreted glypicans have opposing and/or distinct effects on morphogen
      signaling from the membrane-tethered forms.

PMID- 15963975
TI  - Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism
      equally improve endothelial vasodilator function in L-NAME-induced hypertensive
      rats.
AB  - Male Sprague-Dawley rats given N(omega)-nitro-L-arginine methyl ester (L-NAME) in
      drinking water for 8 weeks showed: (1) a clear-cut increase in systolic blood
      pressure; (2) a consistent decrease of endothelial-cell nitric oxide synthase
      (eNOS) gene expression in aortic tissue; (3) a marked reduction of plasma
      nitrite/nitrate concentrations; (4) a reduction of the relaxant activity of
      acetylcholine (ACh, from 10(-10) to 10(-4) M) on norepinephrine-precontracted
      aortic rings (reduction by 48+/-5%); (5) a marked decrease (-58%) of the basal
      release of 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) from aortic rings. In
      L-NAME-treated rats, administration in the last 4 weeks of either the angiotensin
      converting enzyme (ACE) inhibitor enalapril (10 mg/kg/day in tap water) or the
      angiotensin AT(1)-receptor antagonist losartan (10 mg/kg/day in tap water)
      decreased systolic blood pressure levels, completely restored eNOS mRNA levels in
      aortic tissue and plasma nitrite/nitrate levels, and allowed a consistent
      recovery of both the relaxant activity of acetylcholine and the generation of 6
      keto-PGF1alpha. Coadministration of icatibant, a bradykinin B(2)-receptor
      antagonist (200 microg/kg/day), with enalapril blunted the stimulatory effect of
      the ACE inhibitor on eNOS mRNA expression, circulating levels of nitrite/nitrate,
      the relaxant activity of ACh and the release of 6-keto-PGF1alpha in L-NAME
      treated rats. The generation of 6-keto-PGF1alpha from aortic rings was also
      decreased in rats coadministered icatibant with losartan. These findings indicate
      that (1) the ACE inhibitor enalapril and the angiotensin AT(1)-receptor blocker
      losartan are equally effective to reverse NAME-induced endothelial dysfunction;
      (2) the beneficial effect of enalapril on the endothelial vasodilator function in
      L-NAME-treated rats is mediated by bradykinin B(2)-receptor activation; and (3)
      the enhanced endothelial generation of prostacyclin induced by losartan in L-NAME
      rats is also mediated by bradykinin B(2)-receptor activation.

PMID- 15963976
TI  - Mitochondrial dysfunction is related to necrosis-like programmed cell death
      induced by A23187 in CEM cells.
AB  - We have previously reported that calcium ionophore A23187 differentially induces
      necrosis in CEM cells, a T-lymphoblastic leukemia cell line, and apoptosis in
      HL60 cells, a promyelocytic leukemia cell line. Stimulation with VP16, however,
      induces typical apoptosis in both cell lines. Necrosis in CEM cells,
      characterized by cell shrinkage and clustering, began within 5 min of treatment.
      Swelling of the mitochondria, lumpy chromatin condensation and intact plasma
      membranes were evident by electron microscopy. These A23187-mediated changes in
      CEM cells were suppressed by clonazepam or CGP37157, inhibitors of the
      mitochondrial Na(+)/Ca(2+) exchanger. The changes, however, were not affected by
      cyclosporin A, an inhibitor of the mitochondrial permeability transition pore. In
      both CEM and HL60 cells, intra-cellular calcium increased with similar amplitude
      within 1 min of treatment with 2 microM A23187. Intra-mitochondrial calcium
      increased with clonazepam pre-treatment alone in both CEM and HL60 cells.
      However, intra-mitochondrial calcium did not change drastically in response to
      A23187 in CEM or HL60 cells, either untreated or pre-treated with clonazepam.
      A23187 induces necrosis in CEM cells concurrent with mitochondrial dysfunction,
      which is independent of the mitochondrial permeability transition, but affected
      by intra-mitochondrial calcium, while HL60 cells lack these early changes.
      Differences in the responses to A23187 between these two cell lines might derive
      from differences in the susceptibility of the mitochondrial membrane to rapid
      increases in intra-cellular calcium.

PMID- 15963977
TI  - Age-dependent effect of secretagogues during colonic maturation.
AB  - Intestinal secretory response is altered during colonic development. The aim of
      this report was to study the developmental changes of the Ca(2+)- and cAMP
      induced regulatory pathways with special attention to the direct and indirect
      effect of secretagogues on the colonic epithelium. We investigated the effect of
      bethanechol, 5-hydroxytryptamine (5-HT), and histamine on Cl(-) secretion and
      stimulation of intracellular Ca(2+) ([Ca(2+)](i)) and cAMP in the distal colon of
      suckling, weanling and adult rats. In the presence of tetrodotoxin, immature
      colon of suckling and weanling rats displayed higher potency (EC(50)) of 5-HT to
      stimulate Cl(-) secretion, whereas the potency of histamine was not changed
      during development. The potency of bethanechol was reduced during weaning and
      partially restored in adulthood. 5-HT increased cAMP level similarly in both
      neonatal and adult colonic crypts, but the adults had higher basal level of cAMP
      than suckling rats. Also the effect of bethanechol on [Ca(2+)](i) was independent
      of colonic maturation. The results suggest that colonic Cl(-) secretion displays
      developmental changes of regulation depending on the non-neural secretagogue
      signalling pathway and that these developmental changes seem to be localized
      somewhere outside colonocytes.

PMID- 15963978
TI  - Differential action of domperidone to modify emesis and behaviour induced by
      apomorphine in the ferret.
AB  - The action of domperidone (1 mg/kg, i.p.) on spontaneous behaviour and the emesis
      and behavioural change induced by apomorphine (0.25 mg/kg, s.c.) were studied in
      the ferret. Domperidone was inactive to modify spontaneous behaviour but
      apomorphine-induced emesis and increased locomotor activity (distance travelled
      and velocity of movement; P<0.05); the emesis, but not the modification of
      locomotor activity was antagonized significantly (P<0.01) by domperidone.
      However, apomorphine did not modify significantly other behavioural measures
      (i.e. lip licking, rearing, burrowing, backward walking, curling-up activity, or
      defecatory frequency; P>0.05). The action of apomorphine to modify behaviour and
      its interaction with domperidone in this species is discussed in relation to
      animal models of nausea.

PMID- 15963979
TI  - Surface and cytoplasmic immunoglobulin expression in B-cell chronic lymphocytic
      leukemia (CLL).
AB  - Flow cytometric analysis of abnormal lymphocyte populations in chronic
      lymphocytic leukemia (CLL) has been widely reported to show weak expression of
      surface immunoglobulin (sIg). The international scoring system to help
      discriminate between CLL and other B-cell lymphoproliferative disorders lists
      this as the first of 5 criteria worth 1 point each. In the present study, 30
      cases of CLL were studied for surface and cytoplasmic Ig expression. 23 of these
      30 (76.7%) cases were positive for sIg. Of these 23, 14 cases (60.9%) showed
      moderate to bright sIg expression. All of these 23 cases were positive for CD5
      and CD23; all were negative for CD10 and only 6 (26.1%) were positive for FMC7.
      27 of 30 (90.0%) cases expressed cytoplasmic immunoglobulin (cIg) compared to 5%
      reported by others. This shows that cytoplasmic Ig occurs in a much greater
      percentage of cases than reported previously. 23 of 30 (76.7%) cases showed
      positivity for both surface and cytoplasmic Ig, with 15 showing kappa light chain
      restriction and 8 showing lambda light chain restriction. Six expressed
      cytoplasmic Ig only, with 4 showing kappa light chain restriction and 2 showing
      lambda light chain restriction. One case expressed neither cytoplasmic nor
      surface Ig. CD38 positivity portends a worse prognosis. Of the 29 cases tested
      for CD38, 13 (44.8%) were positive. Of these 13 cases, 12 were in the surface
      Ig/cytoplasmic Ig+ group and 1 in the cytoplasmic Ig+ group only. Also, of the 23
      cases tested for CD22 expression, 16 (69.6%) were positive. These data question
      the use of both "weak" surface Ig expression and lack of CD22 expression as valid
      scoring criteria for CLL.

PMID- 15963980
TI  - High-level microsatellite instability is not involved in gallbladder
      carcinogenesis.
AB  - The molecular alterations involved in the pathogenesis of gallbladder cancer are
      not yet well defined. Our aim was to determine the microsatellite status of
      gallbladder carcinomas and its possible correlation with alterations in K-ras and
      p53 genes as well as the clinicopathological characteristics of these tumors. A
      group of 37 gallbladder carcinomas was analyzed for alterations in a proposed
      panel of mononucleotide and dinucleotide markers of microsatellite instability.
      Somatic frameshift mutations at repeated sequences in the coding regions of TGF
      betaRII, Bax, hMSH3, hMSH6 were also examined. The findings were correlated with
      the presence of K-ras and p53 alterations, and tumors' clinicopathological
      features. Microsatellite instability and/or LOH was observed in 9 gallbladder
      carcinomas. Cases showing microsatellite instability displayed alterations only
      in dinucleotide markers and were classified as MSI-L carcinomas. A subset of
      gallbladder carcinomas is characterized by low-level instability, based on the
      analysis of the above mentioned panel of markers. The pathway of microsatellite
      instability seems to play a minor role in the pathogenesis of gallbladder cancer.

PMID- 15963981
TI  - Adiponectin stimulates human osteoblasts proliferation and differentiation via
      the MAPK signaling pathway.
AB  - Adipocytes can highly and specifically express adiponectin, and the adiponectin
      receptor (AdipoR) has been detected in bone-forming cells. The present study was
      undertaken to investigate the action of adiponectin on osteoblast proliferation
      and differentiation. AdipoR1 protein was detected in human osteoblasts.
      Adiponectin promoted osteoblast proliferation and resulted in a dose- and time
      dependent increase in alkaline phosphatase (ALP) activity, osteocalcin and type I
      collagen production, and an increase in mineralized matrix. Suppression of
      AdipoR1 with small-interfering RNA (siRNA) abolished the adiponectin-induced cell
      proliferation and ALP expression. Adiponectin induces activation of p38 mitogen
      activated protein kinase (MAPK) and c-jun N-terminal Kinase (JNK), but not ERK1/2
      in osteoblasts, and these effects were blocked by suppression of AdipoR1 with
      siRNA. Furthermore, pretreatment of osteoblasts with the JNK inhibitor SP600125
      abolished the adiponectin-induced cell proliferation. p38 inhibitor SB203580
      blocked the adiponectin-induced ALP activity. These data indicate that
      adiponectin induces human osteoblast proliferation and differentiation, and the
      proliferation response is mediated by the AdipoR/JNK pathway, while the
      differentiation response is mediated via the AdipoR/p38 pathway. These findings
      suggest that osteoblasts are the direct targets of adiponectin.

PMID- 15963982
TI  - Overexpression of RhoA-GTP induces activation of the Epidermal Growth Factor
      Receptor, dephosphorylation of focal adhesion kinase and increased motility in
      breast cancer cells.
AB  - Rho GTPases are overexpressed in human tumors and are involved in a variety of
      cellular processes such as organization of the actin cytoskeleton, cell-cell
      contact and malignant transformation. EGFR activation plays a key role in the
      acquisition of motile properties in carcinoma cells, and it has been proposed
      that downregulation of FAK activity is one of its most relevant consequences. In
      the present study, using mammary MCF-7 cells, we demonstrated that overexpression
      of the active form of the small GTPase RhoA induced the activation of EGFR by a
      phenomenon that depends on the activity of a metalloproteinase (MMP), which
      presumably cleaves a membrane-bound EGFR ligand. The EGFR tyrosine
      phosphorylation correlates with ERK1,2 activation and the stimulation of
      urokinase production. An aggressive mammary cell line (MDA-MB-231) that
      overexpresses both RhoA and EGFR in their active forms also displayed an MMP
      dependent activation mechanism of EGFR. RhoA-GTP-transfected cells showed a
      cortical array of F-actin, rounded morphology, reduced spreading potential and a
      dephosphorylation of FAK that was released by integrin-dependent fibronectin
      adhesion and a specific EGFR tyrosine kinase inhibitor. Our results suggest that
      the MMP-dependent EGFR activation observed in V14 RhoA cells represents the
      starting point of a signaling route that promotes cell motility by activation of
      ERK1,2 and further enhancement of proteases production.

PMID- 15963983
TI  - Suppression of laminin-5 expression leads to increased motility, tumorigenicity,
      and invasion.
AB  - Laminin-5 (Ln-5) is expressed in several human carcinomas and hypothesized to
      contribute to tumor invasion. To understand the role of Ln-5 in human cancers, we
      stably delivered small interfering RNAs (siRNAs) directed against the Ln-5 gamma2
      chain into JHU-022-SCC cells (022), a non-invasive oral squamous cell carcinoma
      (OSCC) cell line which secretes Ln-5. Lysates from gamma2 siRNA cells (022
      sigamma2) had nearly undetectable levels of the gamma2 chain while the alpha3 and
      beta3 subunits of Ln-5 remained unchanged compared to parental and control. In
      conditioned medium from 022-sigamma2 cells, the gamma2 chain and the Ln-5
      heterotrimer were barely detectable, similar to an invasive OSCC cell line.
      Conditioned medium from 022-sigamma2 cells contained less alpha3 and beta3
      subunits than both parental and control. Although the proliferation and adhesive
      properties of the 022-sigamma2 cells remained similar to parental and control
      cells, 022-sigamma2 cells showed increased detachment and a fibroblastic
      morphology similar to invasive cells. Moreover, migration, in vitro invasion, and
      in vivo tumorigenicity were enhanced in 022-sigamma2 cells. Our results suggest
      that the Ln-5 gamma2 chain regulates the secretion of the alpha3 and beta3
      subunits. More importantly, suppression of Ln-5 results in a phenotype that is
      representative of invasive tumor cells.

PMID- 15963984
TI  - Do mice genetically selected for resistance to oral tolerance provide selective
      advantage for Schistosoma mansoni infection?
AB  - A highly evolved relationship exists between the parasitic flatworm Schistosoma
      mansoni and its vertebrate hosts that include the use of host immune signals by
      parasites. The S. mansoni infection was studied in two strains of mice
      genetically selected, over 18 generations of assortative mating, for extreme
      phenotypes of susceptibility (TS) and resistance (TR) to immunological tolerance.
      The objective was to observe whether the different host genetic backgrounds
      affected the outcome of experimental schistosomiasis. Fecal egg excretion, tissue
      egg count, worm recovery, and adult worm morphology and morphometry were
      monitored throughout the period of infection. TR mice presented total fecal egg
      excretion and thickness of tegument in adult male worms significantly higher than
      TS mice. Therefore, the comparative analysis of mice with extreme phenotypes of
      immunological response turns out to be useful in host-parasite relationship
      studies. Our results suggest that the TR mouse immunological profile provides a
      more favorable environment for the development of S. mansoni.

PMID- 15963985
TI  - Trypanosoma cruzi: distinct patterns of infection in the sibling caviomorph
      rodent species Thrichomys apereoides laurentius and Thrichomys pachyurus
      (Rodentia, Echimyidae).
AB  - Thrichomys apereoides, a caviomorph rodent species common in a highly endemic
      area for Chagas disease in Brazil, may act as reservoir of the parasite. However,
      no information is available concerning its sibling species Thrichomys pachyurus,
      found in the Pantanal region, where Trypanosoma cruzi is found only in the
      enzootic cycle. We followed up the cross infection of these cryptic species with
      two isolates derived from naturally infected T. pachyurus and Thrichomys
      apereoides laurentius. No regional co-adaptation between Thrichomys species and
      the regional isolates were noticed. However, significant differences in the
      outcome of the infection were observed. T. a. laurentius was more resistant than
      T. pachyurus, as expressed by lower parasitemia and less histopathological
      damage. The routine biochemical markers used for laboratory rodents were
      unsuitable for follow up of infection in Thrichomys spp, since they did not
      correlate with the histopathological findings or allowed the kinetic follow-up of
      tissue colonization by the parasite.

PMID- 15963986
TI  - Cooperative effect of hydrophobic and electrostatic forces on alcohol-induced
      alpha-helix formation of alpha1-acid glycoprotein.
AB  - Alpha1-acid glycoprotein (AGP) is a serum glycoprotein that mainly binds basic
      drugs. Previous reports have shown that AGP converts from a beta-sheet to an
      alpha-helix upon interaction with biomembranes. In the current studies, we found
      that alkanols, diols, and halogenols all induce this conformational change.
      Increased length and bulkiness of the hydrocarbon group and the presence of a
      halogen atom promoted this conversion, whereas the presence of a hydroxyl group
      inhibited it. Moreover, the effect was dependent on the hydrophobic and
      electrostatic properties of the alcohols. These results indicate that, in a
      membrane environment, hydrophobic and electrostatic factors cooperatively induce
      the transition of AGP from a beta-sheet to an alpha-helix.

PMID- 15963987
TI  - Viroporin activity of murine hepatitis virus E protein.
AB  - The viroporin activity of the E protein from murine hepatitis virus (MHV), a
      member of the coronaviruses, was analyzed. Viroporins are a growing family of
      viral proteins able to enhance membrane permeability, promoting virus budding.
      Initially, the MHV E gene was inducibly expressed in Escherichia coli cells,
      leading to the arrest of bacterial growth, cell lysis and permeabilization to
      different compounds. Thus, exit of labeled nucleotides from E. coli cells to the
      cytoplasm was apparent upon expression of MHV E. In addition, enhanced entry of
      the antibiotic hygromycin B occurred at levels comparable to those observed with
      the viroporin 6K from Sindbis virus. Mammalian cells are also readily
      permeabilized by the expression of MHV E protein. Finally, brefeldin A powerfully
      blocks the viroporin activity of the E protein in BHK cells, suggesting that an
      intact vesicular system is necessary for this coronavirus to permeabilize
      mammalian cells.

PMID- 15963988
TI  - TNF-alpha enhances phenotypic and functional maturation of human epidermal
      Langerhans cells and induces IL-12 p40 and IP-10/CXCL-10 production.
AB  - Dendritic cells (DC) play a central role in immunity/tolerance decision,
      depending on their activation/maturation state. TNF-alpha is largely produced in
      the skin under inflammatory conditions. However, it still remains to be defined
      how TNF-alpha modulates the activation status of human LC, the most specialized
      DC controlling skin immunity. Here, we reported that fresh immature LC, highly
      purified from healthy human skin and exposed for two days to TNF-alpha under
      serum-free conditions, expressed up-regulated level of co-stimulatory molecules
      (CD40, CD54, CD86), maturation markers (CD83, DC-LAMP), CCR7 lymph node homing
      receptor, and down-regulated Langerin level, in a dose-dependent manner. This
      mature phenotype is closely associated with enhanced LC allostimulatory capacity.
      Furthermore, TNF-alpha significantly increased the number of viable LC and
      decreased their spontaneous apoptosis. More importantly, TNF-alpha induced LC to
      produce both IFN-gamma-inducible-protein IP-10/CXCL10, a Th1-attracting chemokine
      and IL-12 p40. Bioactive IL-12 p70 was never detected, even after additional CD40
      stimulus. The results implicate LC as an effective target through which TNF-alpha
      may up- or down-regulate the inflammatory skin reactions.

PMID- 15963989
TI  - Comparison of replicative senescence and stress-induced premature senescence
      combining differential display and low-density DNA arrays.
AB  - Human diploid fibroblasts (HDFs) exposed to subcytotoxic stress display many
      features of senescence. Using differential display RT-PCR, gene expression of
      HDFs in premature senescence induced by tert-butylhydroperoxide or ethanol and in
      replicative senescence was compared to gene expression of HDFs at early
      cumulative population doublings. Thirty genes of known function were identified
      from the 265 differentially displayed cDNA fragments. A customized low-density
      array allowed to confirm the relative level of the corresponding 30 transcripts.
      We found differential expression of genes coding for proteins implicated namely
      in growth arrest (PTEN, IGFBP-3, LRP-1 and CAV1), senescent morphogenesis (TGF
      beta1 and LOXL2) and iron metabolism (TFR and FTL).

PMID- 15963990
TI  - Importance of local structures of second and third repeat fragments of
      microtubule-binding domain for tau filament formation.
AB  - To investigate the importance of the seventh residue of the second and third
      repeat fragments (R2 and R3 peptides) of the microtubule-binding domain (MBD) for
      tau filamentous assembly, the residues Lys and Pro were substituted (R2-K7P and
      R3-P7K). The filament formations of the R2 and R3 peptides were almost lost due
      to their substitutions despite their overall conformational similarities. The NOE
      analyses showed the importance of the conformational flexibility for the R2
      peptide and the coupled extended and helical conformations for the R3 peptide in
      their limited N-terminal regions around their seventh residues. The result shows
      that the filament formation of MBD is initiated from a short fragment region
      containing the minimal conformational or functional motif.

PMID- 15963991
TI  - Disulfide-bond formation in the H+-pyrophosphatase of Streptomyces coelicolor and
      its implications for redox control and enzyme structure.
AB  - Redox control of disulfide-bond formation in the H+-pyrophosphatase of
      Streptomyces coelicolor was investigated using cysteine mutants expressed in
      Escherichia coli. The wild-type enzyme, but not a cysteine-less mutant, was
      reversibly inactivated by oxidation. To determine the residues involved in
      oxidative inactivation, different cysteine residues were replaced. Analysis with
      a cysteine-modifying reagent revealed that the formation of a disulfide bond
      between cysteines 253 and 621 was responsible for enzyme inactivation. This
      result suggests that residues in different cytoplasmic loops are close to each
      other in the tertiary structure. Both cysteine residues are conserved in K+
      independent (type II) H+-pyrophosphatases.

PMID- 15963992
TI  - Biomineralization in diatoms: characterization of novel polyamines associated
      with silica.
AB  - Pattern formation during silica biomineralization in diatoms appears to depend on
      long-chain polyamines as well as proteins covalently modified with polyamines
      (silaffins). Recently, the complete genome of the diatom Thalassiosira pseudonana
      has been sequenced making this species an attractive model organism for future
      studies on biomineralization. Mass- and NMR-spectroscopic analysis of the long
      chain polyamines from this diatom species reveals the existence of a complex
      population with as yet unknown structural features. These include complex
      methylation patterns, different attachment moieties as well as the existence of
      quaternary ammonium functionalities.

PMID- 15963993
TI  - Quorum quenching enzyme activity is widely conserved in the sera of mammalian
      species.
AB  - Acyl-homoserine lactone (AHL) quorum sensing signals play a key role in
      synchronizing virulence gene expression in Pseudomonas aeruginosa, which could
      cause fatal bloodstream infections. We showed that AHL inactivation activity,
      albeit with variable efficiency, was conserved in the serum samples of all the 6
      tested mammalian animals. High-performance liquid chromatography and mass
      spectrometry analyses revealed that mammalian sera had a lactonase-like
      enzyme(s), which hydrolyzed the lactone ring of AHL to produce acyl homoserine,
      with enzyme properties reminiscent of paraoxonases (PONs). We further showed that
      the animal cell lines expressing three mouse PON genes, respectively, displayed
      strong AHL degradation activities.

PMID- 15963994
TI  - The properties of the mitochondrial megachannel in mitoplasts from human colon
      carcinoma cells are not influenced by Bax.
AB  - This paper explores the relationship between Bax and the mitochondrial
      permeability transition pore (PTP). Isolated human colon tumor (HCT116) Bax-
      mitochondria exposed to recombinant Bax exhibited a slow, cyclosporin A-sensitive
      swelling, but only at [Bax]>200 nM. The amount of Bax incorporated was much
      higher than that found in organelles isolated from HCT116 Bax+ staurosporine- or
      etoposide-treated apoptotic cells, casting doubts on the significance of the
      putative PT induction for apoptosis. Bax did not influence the
      electrophysiological properties of an approximately 1 nS channel ascribed to the
      Ca2+-dependent mitochondrial permeability transition pore. These observations
      indicate that the PTP is independent of Bax.

PMID- 15963996
TI  - The influence of displacement on shoulder function in patients with minimally
      displaced fractures of the greater tuberosity.
AB  - INTRODUCTION: There is little outcome data on functional results after non
      operative treatment of greater tuberosity fractures, and no clear evidence in
      minimally displaced (1-5 mm) fractures of the greater tuberosity showing that the
      results of non-operative treatments are good enough. This study assesses the
      relationship between degree of displacement in non-operatively treated patients
      and shoulder function. MATERIALS AND METHODS: We evaluated the radiographs and
      function in 135 patients after non-operative treatment of minimally displaced (1
      5 mm) fractures of the greater tuberosity at a mean time of 3.7 years (2-20
      years) after injury. Shoulder function was assessed using the Vienna Shoulder
      Score (VSS), the Constant Score (CS) and the UCLA-Score. RESULTS: 97% of the
      evaluated patients had good or excellent results. Patients with a displacement of
      more than 3 mm had slightly worse results compared to those with less
      displacement, but this was not statistically significant. Female patients had
      significantly better results than male patients, and patients in the eighth and
      ninth decade had significantly worse results compared to younger patients.
      CONCLUSION: We recommend non-operative treatment in all patients with minimally
      displaced fractures of the greater tuberosity, as most obtain very good results.
      The best results followed treatment with Gilchrist bandages or Mitella slings for
      3 weeks, followed by intensive rehabilitation.

PMID- 15963997
TI  - Indirect reduction using a simple quadrilateral frame in the application of
      distal tibial LCP-technical tips.
AB  - Minimally invasive percutaneous plate osteosynthesis (MIPPO) has become widely
      practiced in the operative management of articular, metaphyseal and transitional
      zone fractures. Early indirect reduction of such fractures of the distal tibia
      can be achieved easily using a simple quadrilateral frame. This enables CT
      scanning where required and allows the soft tissues to be assessed with ease.
      Distal tibial anatomical locking compression plates (LCP Synthes UK) have
      recently become available. Retrograde insertion of the AO distal tibial
      anatomical LCP via a distal transverse wound enables the MIPPO to be completed
      rapidly, with minimal surgical trauma to the zone of injury, with the frame in
      place until the procedure is completed-a particular advantage in these often
      highly unstable injuries.

PMID- 15963995
TI  - Rapid effects of aromatase inhibition on male reproductive behaviors in Japanese
      quail.
AB  - Non-genomic effects of steroid hormones on cell physiology have been reported in
      the brain. However, relatively little is known about the behavioral significance
      of these actions. Male sexual behavior is activated by testosterone partly
      through its conversion to estradiol via the enzyme aromatase in the preoptic area
      (POA). Brain aromatase activity (AA) changes rapidly which might in turn be
      important for the rapid regulation of behavior. Here, acute effects of Vorozole,
      an aromatase inhibitor, injected IP at different doses and times before testing
      (between 15 and 60 min), were assessed on male sexual behavior in quail. To limit
      the risk of committing both types of statistical errors (I and II), data of all
      experiments were entered into a meta-analysis. Vorozole significantly inhibited
      mount attempts (P < 0.05, size effect [g] = 0.527) and increased the latency to
      first copulation (P < 0.05, g = 0.251). The treatment had no effect on the other
      measures of copulatory behavior. Vorozole also inhibited appetitive sexual
      behavior measured by the social proximity response (P < 0.05, g = 0.534) or
      rhythmic cloacal sphincter movements (P < 0.001, g = 0.408). Behavioral
      inhibitions always reached a maximum at 30 min. Another aromatase inhibitor,
      androstatrienedione, induced a similar rapid inhibition of sphincter movements.
      Radioenzyme assays demonstrated that within 30 min Vorozole had reached the POA
      and completely blocked AA measured in homogenates. When added to the
      extracellular milieu, Vorozole also blocked within 5 min the AA in POA explants
      maintained in vitro. Together, these data demonstrate that aromatase inhibition
      rapidly decreases both consummatory and appetitive aspects of male sexual
      behavior.

PMID- 15963998
TI  - Pregnancy outcome for Rh-alloimmunized women.
AB  - OBJECTIVE: To compare perinatal results of Rh-alloimmunized pregnancies managed
      with spectrophotometric amniotic fluid analysis or fetal middle cerebral artery
      Doppler ultrasonographic velocimetry. METHOD: A descriptive observational study
      involving 291 consecutive Rh-negative pregnancies. Group 1 consisted of 74
      isoimmunized women managed with amniotic fluid spectrophotometry; group 2 of 25
      isoimmunized women managed with Doppler ultrasonography; and group 3 of 192
      nonimmunized Rh-negative women. The variables analyzed were need for intrauterine
      or neonatal transfusion, mode and time of delivery, birth weight, neonatal
      hematocrit, and perinatal mortality. RESULTS: Need for intrauterine transfusion,
      birth weight, prematurity, rate of cesarean section, and perinatal mortality were
      similar in groups 1 and 2. Neonatal hematocrit was significantly lower and the
      need for neonatal transfusion was significantly higher when spectrophotometry
      rather than Doppler ultrasonographic velocimetry was used. CONCLUSION: Fetuses
      managed with Doppler ultrasonographic velocimetry had a higher hematocrit at
      birth and a lesser need for neonatal transfusion, suggesting that this
      noninvasive method of monitoring fetal anemia is a better choice.

PMID- 15963999
TI  - Comparison of clinical and ultrasonographic estimation of fetal weight.

PMID- 15964000
TI  - Biofilm formation on catheters used after cesarean section as observed by
      scanning electron microscopy.

PMID- 15964001
TI  - Liquid-based cytologic specimen studies to screen for cervical dysplasia in rural
      El Salvador.
AB  - OBJECTIVE: To evaluate an alternative tool (ThinPrep; Cytye Corporation,
      Boxborough, Mass, USA) for cervical cancer screening in rural El Salvador.
      METHODS: Cervical samples were obtained from 471 women attending health fairs in
      rural El Salvador. The samples were read by American and Salvadoran pathologists
      after a 1-week training course in liquid-based cytologic studies in the United
      States. RESULTS: The system evaluated detected a significantly higher number of
      high-grade and above lesions than conventional cytologic studies (P=0.01). There
      were 0.4% and 1.7% of high-grade lesions and above detected with conventionally
      prepared slides in the United States and El Salvador, respectively, and 3.2% and
      3.8% of such lesions detected with liquid-based samples in the United States and
      El Salvador. Intra-observer agreement among the pathologists reading the samples
      was substantial for the ThinPrep system, with a kappa value of 0.6. CONCLUSION: A
      short workshop is effective in training pathologists to use ThinPrep. In the
      studied population, liquid-based studies appear to offer significant advantages
      over conventional cytologic studies for detecting high-grade lesions.

PMID- 15964002
TI  - Management of pregnant women with increased risk of venous thrombosis.
AB  - OBJECTIVE: To evaluate the usefulness of score based management of pregnancies
      with high risk of venous thromboembolism (VTE). METHOD: 116 consecutive
      pregnancies in 109 women with confirmed thrombophilia and/or history of VTE were
      studied. Patients were managed in accordance with international recommendations.
      Recently, a VTE risk prediction score was established. An independent group
      assessed retrospectively and in a blinded way the usefulness of this score.
      RESULTS: Of the 116 pregnancies, an antithrombotic prophylaxis by low molecular
      weight heparin was prescribed in 61 cases (52.6%). All patients with a positive
      score (n=57, 49.1%) have been treated with an antenatal thromboprophylaxis. In
      the population where the score was negative (n=55 cases), none of the patients
      received antenatal prophylaxis. But, despite a negative score, four patients were
      treated by their general practitioner. During the study period, there was only
      one episode of VTE. CONCLUSION: Implementing this scoring system has resulted in
      favorable outcomes and a low risk of recurrent thrombosis in this limited series
      of women with increased risk of VTE.

PMID- 15964003
TI  - Postcircumcision epidermoid inclusion cyst of the vulva containing multiple
      stones.

PMID- 15964004
TI  - The impact of workplace violence on nurses in South Taiwan.
AB  - The purpose of this study was to explore the prevalence of workplace violence
      (WPV) committed by patients and their family members against healthcare workers
      in south Taiwan. WPV incident questionnaires were completed by 205 nurses from a
      medical facility in south Taiwan. Sixty-two percent of the nurses reported
      experiencing WPV. The majority of the cases consisted of verbal abuse including
      threats of violence or threatening words from patients or families. The verbal
      expressions of violence were mainly due to misunderstanding and drunkenness on
      the part of patients and their families, and personal problems in the nurses'
      relationships with doctors and co-workers. The cases of physical WPV reported by
      the nurses were perpetrated by patients who were mentally unstable. The findings
      of this study may help hospitals and nurses in avoiding, reducing, and
      controlling incidents of WPV.

PMID- 15964005
TI  - Burnout, role conflict, job satisfaction and psychosocial health among Hungarian
      health care staff: a questionnaire survey.
AB  - BACKGROUND: There is a growing interest in the psychosocial work environment of
      health care staff since they are at high risk for burnout, role conflict and job
      dissatisfaction. Burnout, as a type of prolonged response to chronic job-related
      stressors, has a special significance in health care where staff experience both
      psychological-emotional and physical stress. Burnout and the other negative
      aspects of the job of health care staff have major behavioural and health
      implications. OBJECTIVES: The present study investigated the interrelationships
      among burnout, role conflict and job satisfaction in a sample of Hungarian health
      care staff. The study also investigated how these indicators of psychosocial work
      climate influence respondents' frequency of psychosomatic symptoms. DESIGN: A
      questionnaire survey (anonymous questionnaires) has been carried out to detect
      these interrelationships. SETTINGS: Two major hospitals in Szeged, Hungary.
      PARTICIPANTS: Questionnaires were distributed to 450 health care staff among whom
      55.7% were registered nurses. All together, 201 questionnaires were returned and
      analyzed, giving a response rate of 44.6%. METHODS: Questionnaire contained items
      on work and health-related information (i.e., burnout, job satisfaction, role
      conflict, and psychosomatic symptoms) and on some basic sociodemographics. Beyond
      descriptive statistics, correlation and multiple regression analyses were
      computed. RESULTS: Findings show that emotional exhaustion and depersonalization
      scores were higher, while scores on personal accomplishment was lower as compared
      to Canadian, Norwegian or US samples. Burnout, particularly emotional exhaustion
      (p<.001), was found to be strongly related to job dissatisfaction. Schooling was
      inversely related to satisfaction with the job (p<.05). While job satisfaction
      was a negative predictor of each type of burnout subscale (p<.001), role conflict
      was a factor contributing positively to emotional exhaustion (p<.001) and
      depersonalization scores (p<.001). CONCLUSIONS: The study results underline the
      importance of the role of psychosocial work environment and the
      interrelationships among burnout, role conflict, job satisfaction and
      psychosomatic health among Hungarian health care staff.

PMID- 15964006
TI  - Failure strength of the bovine caudal disc under internal hydrostatic pressure.
AB  - The structure of the disc is both complex and inhomogeneous, and it functions as
      a successful load-bearing organ by virtue of the integration of its various
      structural regions. These same features also render it impossible to assess the
      failure strength of the disc from isolated tissue samples, which at best can only
      yield material properties. This study investigated the intrinsic failure strength
      of the intact bovine caudal disc under a simple mode of internal hydrostatic
      pressure. Using a hydraulic actuator, coloured hydrogel was injected under
      monitored pressure into the nucleus through a hollow screw insert which passed
      longitudinally through one of the attached vertebrae. Failure did not involve
      vertebra/endplate structures. Rather, failure of the disc annulus was indicated
      by the simultaneous manifestation of a sudden loss of gel pressure, a flood of
      gel colouration appearing in the outer annulus and audible fibrous tearing. A
      mean hydrostatic failure pressure of 18+/-3 MPa was observed which was
      approximated as a thick-wall hoop stress of 45+/-7 MPa. The experiment provides a
      measurement of the intrinsic strength of the disc using a method of internal
      hydrostatic loading which avoids any disruption of the complex architecture of
      the annular wall. Although the disc in vivo is subjected to a much more complex
      pattern of loading than is achieved using simple hydrostatic pressurization, this
      latter mode provides a useful tool for investigating alterations in intrinsic
      disc strength associated with prior loading history or degeneration.

PMID- 15964007
TI  - Differential effects of pre-tension on shear wave propagation in elastic media
      with different boundary conditions as measured by magnetic resonance elastography
      and finite element modeling.
AB  - Magnetic resonance elastography (MRE) can non-invasively determine material
      stiffness based on the propagating shear wavelength. Shear wave propagation in a
      finite homogenous isotropic material can be affected by multiple factors. In this
      study we examined the effects of pre-tension and frequency on MRE shear
      measurements of gel phantoms with different boundary conditions, frequencies, and
      geometries. Results from MRE measurements were compared to wave motion theory in
      elastic solids and qualitatively to a finite element (FE) model. Results
      indicated that boundary conditions, geometry and pre-tension are important
      factors to be considered when performing MRE tests on a finite material, and that
      FE modeling can help explore how the shear wave propagation is affected under
      various boundary conditions and axial stresses, among other potential factors.

PMID- 15964008
TI  - Fabricating gold nanoparticle-oxide nanotube composite materials by a self
      assembly method.
AB  - Composition of nanostructured metal particles on oxide tubes (TiO2 and ZrO2) were
      fabricated and characterized. The composite materials were examined by
      transmission electron microscopy, scanning electron microscopy, FT-IR absorption,
      and UV-visible absorption spectra. The results of characterization showed that
      the composites indeed contained both oxide tubes and gold nanoparticles and that
      the gold nanoparticles were intimately associated with the nanotubes.

PMID- 15964009
TI  - Adsorption of fluids in slitlike pores containing a small amount of mobile ions.
AB  - We apply density functional theory to investigate changes in the phase behavior
      of a fluid caused by the presence of mobile ions inside the pore. The approach
      has been based on the fundamental measure density functional theory and on the
      theory of nonuniform electrolytes developed recently by O. Pizio, A. Patrykiejew,
      S. Sokolowski [J. Chem. Phys. 121 (2005) 11,957]. We have evaluated capillary
      condensation phase diagrams for pores of different widths and for different
      concentrations of confined ions. The calculations have demonstrated that the
      presence of ions leads to lowering the critical temperature and to an increase of
      the value of the chemical potential at the capillary condensation point.

PMID- 15964010
TI  - Ultrathin films of tetrasulfonated copper phthalocyanine-capped titanium dioxide
      nanoparticles: fabrication, characterization, and photovoltaic effect.
AB  - Tetrasulfonated copper phthalocyanine (CuTsPc)-capped TiO2 nanoparticle ultrathin
      films were fabricated by a layer-by-layer (LBL) self-assembly technique.
      Alternating bilayer structures were formed by consecutive adsorption of CuTsPc
      capped TiO2 nanoparticles with poly(diallyldimethylammonium chloride). Optical
      and electrical measurements were carried out to characterize the CuTsPc-capped
      TiO2 nanoparticle ultrathin films. Optical measurements revealed uniform
      deposition. The surface morphology of such bilayer films showed a granular
      morphology similar to other classes of LBL films. Electrical measurements
      revealed an abnormal phenomenon under white light illumination. Electrochemical
      and photoelectrochemical measurements on such a bilayer system were carried out
      to elucidate the electron transport processes and the photovoltaic effect.

PMID- 15964011
TI  - Salicylic acid-induced effects in the mixed-lipid (dipalmitoyl
      phosphatidylcholine-dipalmitoyl phosphatidylethanolamine) model membrane.
AB  - The effect of the keratolytic drug salicylic acid (SA) on the thermotropic
      properties and fluidity of the mixed lipid membrane dipalmitoyl
      phosphatidylcholine (DPPC)-dipalmitoyl phosphatidylethanolamine (DPPE) had been
      studied using DSC, (1H and 31P) NMR, SAXS, and dynamic light scattering. The
      membrane was in multilamellar vesicular (MLV) and unilamellar vesicular (ULV)
      form with SA/(DPPC+DPPE) molar ratios, R(m), in the range from 0 to 0.5. It was
      found that the mechanism of interaction of SA with the lipid mixture exhibited
      similar patterns in both ULV and MLV. Both the NMR and DSC studies indicated that
      the drug molecules were probably localized in the lipid-water interfacial region
      neighboring the lipid headgroups or the glycerol moiety. The presence of the drug
      increased the fluidity of the membrane and the acyl chain order. However, studies
      on MLV showed that the presence of the drug in high concentration (R(m)0.2),
      caused destabilization of the DPPC-DPPE mixture, as indicated by the appearance
      of two endothermic transitions. DSC studies indicated that prolonged
      equilibration of the membrane led to reduced interaction between the lipid
      headgroups and the SA molecules. This reduced interaction could be due to the
      sequestering of the drug molecules into the lipid-water interfacial region, out
      of proximity to the polar headgroup or glycerol moiety. Effect of inclusion of
      cholesterol in the membrane systems was also studied.

PMID- 15964012
TI  - Surface properties of various powdered hydroxyapatites.
AB  - Electrophoretic mobilities of various synthetic and semisynthetic hydroxyapatites
      (Ca10(PO4)6(OH)2, HAP) suspended in aqueous solutions have been measured as a
      function of pH and calcium concentration. The studied powders differ in particle
      size, crystallinity degree and surface contamination (carbonate). When
      equilibrated in mineral acids or bases, a large plateau of negative mobility is
      observed in the pH range 5-8, with increasing negative values at higher pH. Only
      in the case of the sample composed of nanoparticles, positive mobility obtains at
      pH < 8.9. When Ca2+ is added, positive mobility values are observed for all
      samples, and a bell-shaped profile results as a function of pH. Two possible
      models are explored to describe the results: the Nernstian approach, which
      assumes solubility equilibrium and surface potentials determined by the three
      potential-determining ions (Ca2+, PO3-4, and OH-), and the surface complexation
      approach, based on the idea of negligible phase transfer of structural phosphate.
      The Nernstian model is inadequate, whereas a very simple surface complexation
      model based on the equations Ca5(PO4)+3 = Ca4(PO4)-3 + Ca2+,Ca4(PO4)-3 + H+ =
      Ca4(PO4)2(PO4H),Ca5(PO4)+3 + OH- = Ca5(PO4)3(OH),coupled with a very simple
      electrical double layer, model suffices to reproduce the bell-shaped profile of
      the mobility as a function of pH in the presence of added calcium salts. The
      results also show that the sample composed of nanoparticles exchanges ions more
      easily with the solution, without reaching the solubility equilibrium in the
      explored timespans. In the presence of soluble phosphate salts, it is postulated
      that the same surface ensembles define the surface charge, with participation of
      phosphate as described by the equation Ca5(PO4)+3 + PO3-4 = Ca4(PO4)-3.HAP is
      just one member of a family of calcium phosphates with different (Ca)/(P) ratios.
      Electrophoretic mobilities of another member, tricalcium diphosphate, Ca3(PO4)2,
      were also measured and shown to be described by the same basic model. Comparison
      with previous literature data shows that the negative plateau in the mobility is
      a general feature of many HAP samples at low Ca2+, again in agreement with the
      surface complexation model. FTIR data demonstrates that surface phosphate indeed
      undergoes protonation, as postulated in the model.

PMID- 15964013
TI  - The structure of the human AGT protein bound to DNA and its implications for
      damage detection.
AB  - O6-Alklyguanine-DNA alkyltransferase (AGT) is an important DNA repair protein
      that protects cells from mutagenesis and toxicity arising from alkylating agents.
      We present an X-ray crystal structure of the wild-type human protein (hAGT) bound
      to double-stranded DNA with a chemically modified cytosine base. The protein
      binds at two different sites: one at the modified base, and the other across a
      sticky-ended DNA junction. The protein molecule that binds the modified cytosine
      base flips the base and recognizes it in its active site. The one that binds ends
      of neighboring DNA molecules partially flips an overhanging thymine base. This
      base is not inserted into the active-site pocket of the protein. These two
      different hAGT/DNA interactions observed in the structure suggest that hAGT may
      not detect DNA lesions by searching for the adduct itself, but rather for
      weakened and/or distorted base-pairs caused by base damage in the duplex DNA. We
      propose that hAGT imposes a strain on the DNA duplex and searches for DNA regions
      where the native structure is destabilized. The structure provides implications
      for pyrimidine recognition, improved inhibitor design, and a possible
      protein/protein interaction patch on hAGT.

PMID- 15964014
TI  - Electrostatic potential of aminoacyl-tRNA synthetase navigates tRNA on its
      pathway to the binding site.
AB  - In the first stage of a diffusion-controlled enzymatic reaction, aminoacyl-tRNA
      synthetases (aaRSs) interact with cognate tRNAs forming non-specific encounters.
      The aaRSs catalyzing the same overall aminoacylation reaction vary greatly in
      subunit organization, structural domain composition and amino acid sequence. The
      diffusional association of aaRS and tRNA was found to be governed by long-range
      electrostatic interactions when the homogeneous negative potential of tRNA fits
      to the patches of positive potential produced by aaRS; one patch for each tRNA
      substrate molecule. Considering aaRS as a molecule with anisotropic reactivity
      and on the basis of continuum electrostatics and Smoluchowski's theory, the
      reaction conditions for tRNA-aaRS diffusional encounters were formulated. The
      domains, categorized as enzymatically relevant, appeared to be non-essential for
      field sculpturing at long distances. On the other hand, a set of complementary
      domains exerts primary control on the aaRS isopotential surface formation.
      Subdividing the aaRS charged residues into native, conservative and non
      conservative subsets, we evaluated the contribution of each group to long-range
      electrostatic potential. Surprisingly, the electrostatic potential landscapes
      generated by native and non-conservative subsets are fairly similar, thus
      suggesting the non-conservative subset is developed specifically for efficient
      tRNA attraction.

PMID- 15964015
TI  - The HIV fusion peptide adopts intermolecular parallel beta-sheet structure in
      membranes when stabilized by the adjacent N-terminal heptad repeat: a 13C FTIR
      study.
AB  - The HIV gp41 protein mediates fusion with target host cells. The region primarily
      involved in directing fusion, the fusion peptide (FP), is poorly understood at
      the level of structure and function due to its toxic effect in expression
      systems. To overcome this, we used a synthetic approach to generate the N70
      construct, whereby the FP is stabilized in context of the adjacent auto
      oligomerization domain. The amide I profile of unlabeled N70 in membranes reveals
      prominent alpha-helical contribution, along with significant beta-structure. By
      truncating the N terminus (FP region) of N70, beta-structure is eliminated,
      suggesting that the FP adopts a beta-structure in membranes. To assess this
      directly, (13)C Fourier-transformed infra-red analysis was carried out to map
      secondary structure of the 16 N-terminal hydrophobic residues of the fusion
      peptide (FP16). The (13)C isotope shifted absorbance of the FP was filtered from
      the global secondary structure of the 70 residue construct (N70). On the basis of
      the peak shift induced by the (13)C-labeled residues of FP16, we directly assign
      beta-sheet structure in ordered membranes. A differential labeling scheme in FP16
      allows us to distinguish the type of beta-sheet structure as parallel. Dilution
      of each FP16-labeled N70 peptide, by mixing with unlabeled N70, shows directly
      that the FP16 beta-strand region self-assembles. We discuss our structural
      findings in the context of the prevailing gp41 fusion paradigm. Specifically, we
      address the role of the FP region in organizing supramolecular gp41 assembly, and
      we also discuss the mechanism by which exogenous, free FP constructs inhibit gp41
      induced fusion.

PMID- 15964016
TI  - Mechanical unfolding of TNfn3: the unfolding pathway of a fnIII domain probed by
      protein engineering, AFM and MD simulation.
AB  - Protein engineering Phi-value analysis combined with single molecule atomic force
      microscopy (AFM) was used to probe the molecular basis for the mechanical
      stability of TNfn3, the third fibronectin type III domain from human tenascin.
      This approach has been adopted previously to solve the forced unfolding pathway
      of a titin immunoglobulin domain, TI I27. TNfn3 and TI I27 are members of
      different protein superfamilies and have no sequence identity but they have the
      same beta-sandwich structure consisting of two antiparallel beta-sheets. TNfn3,
      however, unfolds at significantly lower forces than TI I27. We compare the
      response of these proteins to mechanical force. Mutational analysis shows that,
      as is the case with TI I27, TNfn3 unfolds via a force-stabilised intermediate.
      The key event in forced unfolding in TI I27 is largely the breaking of hydrogen
      bonds and hydrophobic interactions between the A' and G-strands. The mechanical
      Phi-value analysis and molecular dynamics simulations reported here reveal that
      significantly more of the TNfn3 molecule contributes to its resistance to force.
      Both AFM experimental data and molecular dynamics simulations suggest that the
      rate-limiting step of TNfn3 forced unfolding reflects a transition from the
      extended early intermediate to an aligned intermediate state. As well as losses
      of interactions of the A and G-strands and associated loops there are
      rearrangements throughout the core. As was the case for TI I27, the forced
      unfolding pathway of TNfn3 is different from that observed in denaturant studies
      in the absence of force.

PMID- 15964017
TI  - The 5A structure of heterologously expressed plant aquaporin SoPIP2;1.
AB  - SoPIP2;1 is one of the major integral proteins in spinach leaf plasma membranes.
      In the Xenopus oocyte expression system its water channel activity is regulated
      by phosphorylation at the C terminus and in the first cytosolic loop. To assess
      its structure, SoPIP2;1 was heterologously expressed in Pichia pastoris as a His
      tagged protein and in the non-tagged form. Both forms were reconstituted into 2D
      crystals in the presence of lipids. Tubular crystals and double-layered
      crystalline sheets of non-tagged SoPIP2;1 were observed and analyzed by cryo
      electron microscopy. Crystalline sheets were highly ordered and diffracted
      electrons to a resolution of 2.96A. High-resolution projection maps of tilted
      specimens provided a 3D structure at 5A resolution. Superposition of the SoPIP2;1
      potential map with the atomic model of AQP1 demonstrates the generally well
      conserved overall structure of water channels. Differences concerning the
      extracellular loop A explain the particular crystal contacts between oppositely
      oriented membrane sheets of SoPIP2;1 2D crystals, and may have a function in
      rapid volume changes observed in stomatal guard cells or mesophyll protoplasts.
      This crystal packing arrangement provides access to the phosphorylated C terminus
      as well as the loop B phosphorylation site for studies of channel gating.

PMID- 15964018
TI  - Restricted variable residues in the C-terminal segment of HIV-1 V3 loop regulate
      the molecular anatomy of CCR5 utilization.
AB  - The V3 loop of the HIV-1 envelope glycoprotein (Env) is the major determinant for
      coreceptor utilization, but the structural basis for this specificity remains to
      be defined. By characterizing a set of naturally occurring R5 Env variants, we
      demonstrate that Asp324 in the conserved IIGDIR motif of the V3 loop
      (CTRPN(300)NNTRKSIHIGP(311)GRAFYTTGEIIGD(324)IRQAHC) C-terminal segment regulates
      the molecular anatomy of CCR5 utilization. Whereas gp120 subunits with Asp or Asn
      at position 324 were fusogenic with coreceptor chimeras containing either the N
      terminal domain or the body of CCR5, substitution of charged (Glu, Lys) or small
      hydrophobic (Gly, Ala) residues resulted in complete loss of fusogenic activity
      with the N terminus and markedly reduced utilization of the body of CCR5,
      although their ability to use wild-type CCR5 was unchanged. This phenotypic
      conversion was confirmed in both gain and loss of function experiments using Env
      from multiple subtypes. Alignment of sequences of R5 V3 loops (n=599) from the
      HIV database revealed that the mutation of Asp324 in the conserved IIGDIR motif
      is restricted to Asn324, with proportions of 71.5% and 28%, respectively.
      Infection of primary CD4(+)T cells demonstrated that Env bearing Asp324 was less
      sensitive to RANTES, suggesting that Asp or Asn in this position may be crucial
      for viral fitness. The CD4-dependent gp120 binding to CCR5 was decreased when
      Asp324 was replaced with a charged or hydrophobic residue, but unchanged when
      replaced with Asn. Molecular modeling analyses predicted that Asp/Asn324 forms a
      critical H-bond with Asn300. These findings indicate that Asp or Asn at position
      324 of the V3 stem stabilizes the conformation of V3 loop and hence influences
      the intensities of interaction between CD4-activated gp120 and CCR5 which results
      in viral entry.

PMID- 15964019
TI  - Structure and inter-domain interactions of domain II from the blood-stage
      malarial protein, apical membrane antigen 1.
AB  - The malarial surface antigen apical membrane antigen (AMA1), from Plasmodium
      falciparum, is a leading candidate for inclusion in a vaccine against malaria.
      AMA1 is synthesised by mature blood-stages of the parasite and is located
      initially in the apical organelles of the merozoite. Prior to merozoite invasion
      of host erythrocytes, it is processed into a 66 kDa type 1 integral membrane
      protein on the merozoite surface. The pattern of disulphide bonds in AMA1 has
      been the basis for separation of the ectodomain into three domains, with three,
      two and three disulphide bonds, respectively. We have determined the solution
      structure of a 16kDa construct corresponding to the putative second domain of
      AMA1. While circular dichroism and hydrodynamic data were consistent with a
      folded structure for domain II, its NMR spectra were characterised by broad lines
      and significant peak overlap, more typical of a molten globule. Consistent with
      this, domain II bound the fluorescent dye 8-anilino-1-naphthalene sulphonate
      (ANS). We have nonetheless determined a structure, which defines the secondary
      structure elements and global fold. The two disulphide bonds link the N and C
      terminal regions of the molecule, which come together to form a four-stranded
      beta-sheet linked to a short helix. A long loop linking the N and C-terminal
      regions contains four other alpha-helices, the locations of which are not fixed
      relative to the beta-sheet core, even though they are well-defined locally. Very
      recently this region of domain II has been shown to contain the epitope
      recognised by the invasion-inhibitory antibody 4G2, even though it does not
      contain any of the polymorphisms that are regarded as having arisen in response
      to the pressure of immune recognition.

PMID- 15964020
TI  - Preconditioned hyperbaric oxygenation protects the liver against ischemia
      reperfusion injury in rats.
AB  - Hyperbaric oxygen (HBO) therapy is an effective adjunct in treating ischemia
      reperfusion (I/R) injury of brain, small intestine, testis, and crushing
      extremities. This study was designed to test the hypotheses that preconditioning
      the rats with HBO could protect the liver against subsequent I/R injury. Daily
      treatment with one-dose HBO (90 min, 2.5 ATA) was brought about for male Sprague
      Dawley rats for 1 to 3 days before an I/R injury of liver. Hepatic expression of
      heat-shock protein 70 (Hsp70), total concentration of glutathione (GSH), activity
      of catalase, superoxide dismutase (SOD), and serum AST and ALT were estimated
      before and after HBO, as well as after I/R injury. The results showed that
      activity of hepatic catalase was decreased by one dose, but not three doses, of
      HBO as compared with baseline data. However, hepatic Hsp70 expression fluctuated
      insignificantly. AST and ALT increase less in rats preconditioned with one-dose
      HBO as compared with those without HBO or with three-dose HBO. Our results showed
      preconditioning by one-dose HBO protects rat liver against subsequent ischemia
      reperfusion injury.

PMID- 15964021
TI  - Neuropsychiatric symptoms in dementia-frequency, relationship to dementia
      severity and comparison in Alzheimer's disease, vascular dementia and
      frontotemporal dementia.
AB  - Noncognitive behavioral and psychiatric disturbances are common in dementia and
      help in the clinical differentiation of the various subtypes. We studied the
      frequency of neuropsychiatric disturbances, their relationship to dementia
      severity and compared these disturbances in Alzheimer's disease (AD), vascular
      dementia (VaD) and frontotemporal dementia (FTD) using the 12-item
      Neuropsychiatric Inventory (NPI). A total of 98 patients (AD-44, VaD-31, FTD-23)
      were evaluated. All subjects were community dwelling at the time of evaluation.
      The three groups were comparable on global dementia severity and functional
      ability. All patients had clinically significant scores on the NPI with apathy,
      irritability and agitation being very common (>90% of patients). AD and VaD
      patients in Clinical Dementia Rating (CDR) stage 2 had significantly higher
      scores on the total NPI, agitation and disinhibition subscales compared to those
      in CDR stage 1. Mean scores in the domains of aberrant motor behavior,
      disinhibition and appetite/eating behavior differentiated FTD from AD and VaD.
      Neuropsychiatric disturbances in dementia appear to be universal with agitation,
      disinhibition and irritability being more frequent in the later stages. In this
      cohort disinhibition, aberrant motor behavior and appetite/eating disturbances
      could reliably differentiate AD and VaD from FTD. There were no significant
      differences between the neuropsychiatric profiles of AD and VaD.

PMID- 15964022
TI  - Red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits and their
      influence on plasma lipid levels and plasma antioxidant activity in rats fed with
      cholesterol-containing and cholesterol-free diets.
AB  - Bioactive compounds of peels and peeled red Star Ruby (Sunrise) and blond
      qualities of Jaffa grapefruits were analyzed and their antioxidant potential was
      assessed. The dietary fibers were determined according to Prosky et al., the
      total polyphenol content by Folin-Ciocalteu method and measured at 765 nm,
      minerals and trace elements by atomic absorption spectrometer, phenolic and
      ascorbic acids by HPLC and the antioxidant potential by two different antioxidant
      assays (DPPH and beta-carotene linoleate model system). It was found that the
      contents of most studied bioactive compounds in both qualities are comparable.
      Only the contents of total polyphenols and flavonoids were higher in red
      grapefruits, but not significant. The antioxidant potentials of red peeled
      grapefruits and their peels were significantly higher than of blond peeled
      grapefruits and their peels (P<0.05 in both cases). Diets supplemented with
      peeled red and blond qualities of Jaffa grapefruits and their peels have
      increased the plasma antioxidant capacity and improved plasma lipid levels,
      especially in rats fed with cholesterol added diet. In conclusion, both qualities
      of Jaffa grapefruits contain high quantities of bioactive compounds, but the
      antioxidant potential of red grapefruits is significantly higher. Diets
      supplemented with both qualities of Jaffa grapefruits improve the plasma lipid
      levels and increase the plasma antioxidant activity, especially in rats fed with
      cholesterol added diets. Jaffa grapefruits, especially their red Star Ruby
      quality, could be a valuable supplementation for diseases-preventing diets.

PMID- 15964023
TI  - Is the sarcolemmal or mitochondrial K(ATP) channel activation important in the
      antiarrhythmic and cardioprotective effects during acute ischemia/reperfusion in
      the intact anesthetized rabbit model?
AB  - The relative contributions of cardiomyocyte sarcolemmal ATP-sensitive K(+)
      (K(ATP)) and mitochondrial K(ATP) channels in the cardioprotection and
      antiarrhythmic activity induced by K(ATP) channel openers remain obscure, though
      the mitochondrial K(ATP) channels have been proposed to be involved as a
      subcellular mediator in cardioprotection afforded by ischemic preconditioning. In
      the present study, we sought to investigate the effects of administration of ATP
      sensitive K(+) channel (K(ATP)) openers (nicorandil and minoxidil), a specific
      mitochondrial K(ATP) channel blocker (5-hydroxydecanoate (5-HD)) and a specific
      sarcolemmal K(ATP) channel blocker (HMR 1883; (1-[5-[2-(5-chloro-o
      anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methylthiourea) prior to coronary
      occlusion as well as prior to post-ischemic reperfusion on survival rate,
      ischemia-induced and reperfusion-induced arrhythmias and myocardial infarct size
      in anesthetized albino rabbits. The thorax was opened in the left 4th intercostal
      space and after pericardiotomy the heart was exposed. In Group I (n=88),
      occlusion of the left main coronary artery and hence, myocardial ischemia-induced
      arrhythmias was achieved by tightening a previously placed loose silk ligature
      for 30 min. In Group II (n=206), arrhythmias were induced by reperfusion
      following a 20-min ligation of the left main coronary artery. Both in Group I and
      Group II, intravenous (i.v.) administration of nicorandil (0.47 mg/kg), minoxidil
      (0.5 mg/kg), HMR 1883 (3 mg/kg)/nicorandil and HMR 1883 (3 mg/kg)/minoxidil
      before coronary artery occlusion increased survival rate (86%, 75%, 75% and 86%
      vs. 55% in the control subgroup in Group I; 75%, 67%, 67% and 75% vs. 46% in the
      control subgroup in Group II), significantly decreased the incidence and severity
      of life-threatening arrhythmias. In Group II, i.v. administration of nicorandil
      and minoxidil before coronary artery occlusion significantly decreased myocardial
      infarct size. However, i.v. administration of nicorandil or minoxidil before
      reperfusion did neither increase survival rate nor confer any antiarrhythmic or
      cardioprotective effects. The antiarrhythmic and cardioprotective effects of both
      nicorandil and minoxidil were abolished by pretreating the rabbits with 5-HD (5
      mg/kg, i.v. bolus), a selective mitochondrial K(ATP) channel blocker but not by
      HMR 1883 (3 mg/kg). In the present study, higher levels of malondialdehyde (MDA)
      and lower levels of reduced glutathione (GSH) and superoxide dismutase (SOD) in
      necrotic zone of myocardium in all the 16 subgroups in Group II suggest little
      anti-free radical property of nicorandil and minoxidil. We conclude that
      intervention by intravenous administration of nicorandil and minoxidil (through
      the selective activation of mitochondrial K(ATP) channels) increased survival
      rate and exhibited antiarrhythmic and cardioprotective effects during coronary
      occlusion and reperfusion in anesthetized rabbits when administered prior to
      coronary occlusion. The cardiomyocyte mitochondrial K(ATP) channel may be a
      pharmacologically modulable target of cardioprotection and antiarrhythmic
      activity.

PMID- 15964024
TI  - Exercise training attenuates blood pressure elevation and adverse remodeling in
      the aorta of spontaneously hypertensive rats.
AB  - OBJECTIVE: To observe the extracellular matrix modifications and quantify the
      structural alterations of the aortic wall in spontaneously hypertensive rats
      (SHR) submitted to an aerobic physical activity (PA) protocol. MATERIAL AND
      METHODS: Three groups of five rats each were studied: sedentary normotensive
      Wistar rats (SED-Wistar) and SHR (divided in SHR that underwent a 1 h/day 5
      days/week PA for 20 weeks (EX-SHR) and those that were restricted to cage-bound
      activity (SED-SHR). RESULTS: BP was lower in EX-SHRs and SED-Wistar rats (-35%)
      than in SED-SHRs. This difference became significant from the 3rd week of PA. The
      wall thickness was smaller in the EX-SHR and SED-Wistar (-45%) than in the SED
      SHR (p<0.0001). In EX-SHR group, oxytalan and elaunin fibers were more pronounced
      than in the other groups, while SED-SHR and SED-Wistar rats showed an equivalent
      appearance of aortic elaunin fibers. EX-SHR and SED-Wistar rats showed more than
      65% greater smooth muscle nuclei numerical density per unit area than SED-SHRs
      while SED-SHRs showed more than 45% smaller surface density of lamellae than both
      EX-SHR and SED-Wistar rats. However, no quantitative differences were found in
      the aortic wall comparing EX-SHR and SED-Wistar rats. CONCLUSION: PA might alter
      the aortic wall remodeling to adapt the artery to a hyperkinetic blood flow
      resulting in alterations of the extracellular matrix modulation and vascular
      resistance.

PMID- 15964025
TI  - Albumin enhances the diffusion of lipophilic drugs into the membrane bilayer.
AB  - In earlier work, we reported on the manner with which lipophilic drug molecules
      interact with the cell membrane in order to (a) enter the bilayer and laterally
      diffuse to their respective protein sites of action, or (b) penetrate this
      biological barrier to reach the cell interior. A remaining uncertainty is how
      lipophilic molecules reach the hydrophobic membrane core after traversing the
      aqueous medium and membrane polar surface. Here we present preliminary data using
      deuterium NMR, demonstrating the role of bovine serum albumin in facilitating
      this process. Our observation allows us to postulate a mechanism by which the
      passive transport of lipophilic ligands across the membrane can be greatly
      enhanced through the assistance of carrier proteins.

PMID- 15964026
TI  - Arsenic induced blood and brain oxidative stress and its response to some thiol
      chelators in rats.
AB  - Chronic arsenic toxicity is a widespread problem, not only in India and
      Bangladesh but also in various other regions of the world. Exposure to arsenic
      may occur from natural or industrial sources. The treatment that is in use at
      present employs administration of thiol chelators, such as meso 2,3
      dimercaptosuccinic acid (DMSA) and sodium 2,3-dimercaptopropane 1-sulfonate
      (DMPS), which facilitate its excretion from the body. However, these chelating
      agents are compromised with number of limitations due to their lipophobic nature,
      particularly for their use in cases of chronic poisoning. During chronic
      exposure, arsenic gains access into the cell and it becomes mandatory for a drug
      to cross cell membrane to chelate intracellular arsenic. To address this problem,
      analogs of DMSA having lipophilic character, were examined against chronic
      arsenic poisoning in experimental animals. In the present study, therapeutic
      efficacy of meso 2,3-dimercaptosuccinic acid (DMSA), sodium 2,3-dimercaptopropane
      1-sulfonate (DMPS), monoisoamyl DMSA (MiADMSA) were compared in terms of reducing
      arsenic burden, as well as recovery in the altered biochemical variables
      particularly suggestive of oxidative stress. Adult male Wistar rats were given
      100-ppm arsenic for 10 weeks followed by chelation therapy with the above
      chelating agents at a dose of 50 mg/Kg (orally) once daily for 5 consecutive
      days. Arsenic exposure resulted in marked elevation in reactive oxygen species
      (ROS) in blood, inhibition of ALAD activity and depletion of GSH. These changes
      were accompanied by significant decline in blood hemoglobin level. MiADMSA was
      the most effective chelator in reducing ROS in red blood cells, and in restoring
      blood ALAD compared to two other chelators. Brain superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) decreased, while ROS and TBARS increased
      significantly following arsenic exposure. There was a significant increase in the
      activity of glutathione-S-transferase (GST) with a corresponding decline in its
      substrate i.e. glutathione. Among all the three chelators, MiADMSA showed maximum
      reduction in the level of ROS in brain. Additionally, administration of MiADMSA
      was most effective in counteracting arsenic induced inhibition in brain ALAD, SOD
      and GPx activity. Based on these results and in particular higher metal
      decorporation from blood and brain, we suggest MiADMSA to be a potential drug of
      choice for the treatment of chronic arsenic poisoning. However, further studies
      are required for the choice of appropriate dose, duration of treatment and
      possible effects on other major organs.

PMID- 15964027
TI  - Attenuation of capsaicin-induced acute and visceral nociceptive pain by alpha-
      and beta-amyrin, a triterpene mixture isolated from Protium heptaphyllum resin in
      mice.
AB  - The triterpene mixture, alpha- and beta-amyrin, isolated from Protium
      heptaphyllum resin was evaluated on capsaicin-evoked nociception in mice. Orally
      administered alpha- and beta-amyrin (3 to 100 mg/kg) significantly suppressed the
      nociceptive behaviors--evoked by either subplantar (1.6 microg) or intracolonic
      (149 microg) application of capsaicin. The antinociception produced by alpha- and
      beta-amyrin against subplantar capsaicin-induced paw-licking behavior was neither
      potentiated nor attenuated by ruthenium red (1.5 mg/kg, s.c.), a non-specific
      antagonist of vanilloid receptor (TRPV1), but was greatly abolished in animals
      pretreated with naloxone (2 mg/kg, s.c.), suggesting an opioid mechanism.
      However, participation of alpha2-adrenoceptor involvement was unlikely since
      yohimbine (2 mg/kg, i.p.) pretreatment failed to block the antinociceptive effect
      of alpha- and beta-amyrin in the experimental model of visceral nociception
      evoked by intracolonic capsaicin. The triterpene mixture (3 to 30 mg/kg, p.o.)
      neither altered significantly the pentobarbital sleeping time, nor impaired the
      ambulation or motor coordination in open-field and rota-rod tests, respectively,
      indicating the absence of sedative or motor abnormality that could account for
      its antinociception. Nevertheless, alpha- and beta-amyrin could significantly
      block the capsaicin (10 mg/kg, s.c.)-induced hyperthermic response but not the
      initial hypothermia. These results suggest that the triterpene mixture, alpha-
      and beta-amyrin has an analgesia inducing effect, possibly involving vanilloid
      receptor (TRPV1) and an opioid mechanism.

PMID- 15964028
TI  - Tetrahydrocannabinol suppresses immune function and enhances HIV replication in
      the huPBL-SCID mouse.
AB  - Epidemiologic studies identify marijuana as a potential cofactor in the
      development and progression of HIV infection. To evaluate this interaction we
      employed a hybrid model in which human peripheral blood leukocytes (PBL) were
      implanted into severe combined immunodeficient mice (huPBL-SCID) and infected
      with an HIV reporter construct in the presence or absence of tetrahydrocannabinol
      (THC) exposure. Administration of THC alone, in the absence of HIV, decreased CD4
      counts and the CD4:CD8 ratio. Co-administration of THC and HIV did not reduce CD4
      counts further, but significantly increased the percentage of HIV-infected PBL
      when compared to saline-treated animals (17+/-4.6% vs. 7+/-1.4%). Quantitative
      PCR confirmed a 50-fold increase in systemic viral load in THC-treated animals.
      The CCR5 and CXCR4 chemokine receptors function as coreceptors essential for HIV
      infection. Administration of THC for 5 days increased the percentage of PBL
      expressing CCR5 and, to a lesser extent, CXCR4. This effect was lost after 10
      days of THC administration, but the number of HIV-infected cells had
      significantly increased by that time suggesting a role for early upregulation of
      these coreceptors in the pathogenic effect of THC. Finally, the impact of
      treatment on the number of human interferon-gamma (IFN-gamma) producing cells was
      determined by ELISPOT. Both THC and HIV infection independently decreased the
      number of IFN-gamma producing cells and co-administration produced additive
      effects. These results suggest that exposure to THC in vivo can suppress immune
      function, increase HIV coreceptor expression, and act as a cofactor to
      significantly enhance HIV replication.

PMID- 15964029
TI  - Effect of insulin-mimetic vanadyl sulfate on cytochrome P450 2E1-dependent p
      nitrophenol hydroxylation in the liver microsomes of streptozotocin-induced type
      1 diabetic rats.
AB  - CYP2E1 is known to be induced in streptozotocin (STZ)-treated diabetic rats (STZ
      rats), and its induction is improved by insulin. We have examined the age
      dependent changes of CYP2E1 in the liver microsomes of type 1 diabetic STZ rats,
      the effects of VOSO4 on the contents of total P450 and CYP2E1, and the activities
      of CYP2E1 in terms of p-nitrophenol hydroxylation. The contents of P450 and
      CYP2E1 and CYP2E1 activity were enhanced with the development of diabetes. When
      the hyperglycemia of STZ rats was improved by daily intraperitoneal injections of
      VOSO4 for 10 days at the doses of 7 mg/kg body weight for 5 days, 5 mg/kg for the
      following 3 days, and then 2.5 mg/kg for 2 days, the P450 and CYP2E1 levels and
      CYP2E1 activity were lowered than those in the untreated STZ rats. To understand
      the mechanism underlying CYP2E1-dependent hydroxylation activity, the production
      of reactive oxygen species was examined in the NADPH-liver microsomal systems by
      ESR spin-trapping. Singlet oxygen (1O2) was detected in all microsomal systems,
      while superoxide anion radical(*O2-) and hydroxyl radical (*OH) were not. On the
      basis of these results, we conclude that (1) CYP2E1 level and activity are
      enhanced in the diabetic state, however, they are improved by VOSO4 treatment,
      and (2) 1O2 is generated during CYP2E1-dependent substrate oxygenation.

PMID- 15964030
TI  - Discovery metabolite profiling--forging functional connections between the
      proteome and metabolome.
AB  - Of primary interest for every enzyme is the identification of its physiological
      substrates. However, the vast structural diversity of endogenous metabolites,
      coupled with the overlapping activities of numerous enzymes, makes it difficult
      to deduce the identity of natural substrates for a given enzyme based on in vitro
      experiments. To address this challenge, we recently introduced an LC-MS based
      analytical method termed discovery metabolite profiling (DMP) to evaluate the
      global metabolic effects of enzyme inactivation in vivo. We have applied DMP to
      study mice lacking the enzyme fatty acid amide hydrolase (FAAH), which degrades
      the endocannabinoid family of signaling lipids. DMP identified several previously
      uncharacterized FAAH substrates, including a structurally novel class of brain
      lipids that represent conjugates of very long chain fatty acids with the amino
      acid derivative taurine [N-acyl taurines (NATs)]. These findings show that DMP
      can establish direct connections between the proteome and metabolome and thus
      offers a powerful strategy to assign physiological functions to enzymes in the
      post-genomic era.

PMID- 15964031
TI  - Iptakalim, opener of K(ATP), reverses the enhanced expression of genes encoding
      K(ATP) subunits in spontaneously hypertensive rats.
AB  - ATP-sensitive potassium channels (K(ATP)) are thought to be targets for
      antihypertensive drugs that are potassium channel openers. In this study, the
      expression of genes encoding the K(ATP) subunits, SUR2, Kir6.1 and Kir6.2, was
      detected in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats
      (SHR), and SHR undergoing long-term treatment with iptakalim, a novel
      antihypertensive drug that acts via K(ATP). The transcript levels for SUR2,
      Kir6.1 and Kir6.2 in the heart, aortic smooth muscle, and tail artery smooth
      muscle were determined by reverse transcription-polymerase chain reaction (RT
      PCR). In general, Kir6.2 and SUR2 were more highly represented in all SHR tissues
      compared with those of WKY, and transcripts of Kir6.2 were significantly higher
      in tail artery smooth muscle from SHR. Following long-term treatment with
      iptakalim, mRNA levels of Kir6.2 and SUR2 were reduced significantly in all
      tissues compared with those of untreated SHR. Kir6.1 expression was not
      significantly different between SHR and WKY, and was unaffected by iptakalim
      treatment. These results indicate that the expression of the K(ATP) subunits
      genes, SUR2 and Kir6.2, are closely associated with hypertensive pathological
      states, and the effect of iptakalim on K(ATP) mRNA levels may explain, in part,
      the effects of iptakalim in reversing vascular and cardiac remodeling.
      Furthermore, changes in Kir6.2 mRNA levels suggest that Kir6.x, as well as SUR,
      is responsible for drug binding.

PMID- 15964032
TI  - Orthotopic transplantation of LH receptor knockout and wild-type ovaries.
AB  - Luteinizing hormone (LH) receptor knockout animals have an ovarian failure due to
      an arrest in folliculogenesis at the antral stage. As a result, the animals have
      an infertility phenotype. The present study was undertaken to determine whether
      this phenotype could be reversed by orthotopic transplantation of wild-type
      ovaries. The results revealed that transplanting wild-type ovaries into null
      animals did not result in resumption of estrus cycles. Although the number of
      different types of follicles increased, none progressed to ovulation. The serum
      hormone profiles improved, reflecting the ovarian changes. The wild-type animals
      with null ovaries also failed to cycle and their ovaries and serum hormone levels
      were more like null animals with their own ovaries. Although the lack of rescue
      of null ovaries placed into wild-type animals was predicted, the failure of wild
      type ovaries placed in null animals was not, which could be due to chronic
      exposure of transplanted tissue to high circulating LH levels and also possibly
      due to altered internal milieu in null animals. These findings may have
      implications for potential future considerations of grafting normal donor ovaries
      into women who have an ovarian failure resulting from inactivating LH receptor
      mutations.

PMID- 15964033
TI  - Modifications in P62 occur due to proteasome inhibition in alcoholic liver
      disease.
AB  - P62 is capable of binding the polyubiquitin chain that targets proteins for
      degradation by the proteasome through its ubiquitin associated domain (UBA).
      Immunostaining of hepatocytes from human liver with alcoholic hepatitis showed
      colocalization of ubiquitin and P62 in Mallory bodies. Rats fed ethanol
      chronically and their controls showed that P62 is colocalized with the proteasome
      in hepatocytes as shown by confocal microscopy. P62 cosedimented with 26S
      proteasomes isolated from livers of control and alcohol fed rats. P62 was
      increased in the 26S proteasome fraction when the proteasome chymotrypsin-like
      (ChT-L) activity decreased in rats fed ethanol. PS-341, a potent proteasome
      inhibitor was used to compare the inhibition of the proteasome with the
      inhibition which occurs with ethanol feeding. P62 protein levels were also
      increased in the purified proteasome fraction of rats given PS-341. This data
      indicates that modifications in P62 occur due to proteasome inhibition in
      experimental alcoholic liver disease.

PMID- 15964034
TI  - Identifying sources and distributions of sediment contaminants at two US Virgin
      Islands marinas.
AB  - Differences in sediment contaminant concentrations within two marinas and
      adjacent to the marinas in St. Thomas, US Virgin Islands were compared to
      calculate the portion of those contaminants due to marina activities. In marina 1
      (containing no vessel maintenance areas, but with a fuel dock) 88% of observed
      PAHs and 0% of metals were attributed to marina activities. In the
      marina/boatyard complex, 46% of PAHs and 89% of metals were attributed to marina
      sources. The distance from storm drain discharges, and sediment characteristics
      play a greater role in the distribution and fate of pollutants than do activities
      associated with a given marina station. The data also provided some evidence that
      the protection marinas offer to vessels from wind, currents, and waves may
      concentrate contaminants.

PMID- 15964035
TI  - The implicit sequence learning deficit in patients with Parkinson's disease: a
      matter of impaired sequence integration?
AB  - Despite the wealth of research investigating the serial reaction time (SRT)
      learning abilities of people with Parkinson's disease (PD), the role of the basal
      ganglia in implicit sequence learning remains largely unclear. The present
      research sought to examine the ability of people with PD to implicitly learn
      simultaneously operating sequences and integrate patterned information from each
      sequence dimension. Using a version of the SRT which reduced motor demands, the
      present experiment investigated the implicit learning of a spatial sequence, a
      stimulus-response sequence, and an integrated spatial/stimulus-response sequence,
      all of which are usually confounded in the standard SRT task. Whereas both PD and
      control groups demonstrated robust learning for the individual spatial and
      response sequences, only control participants evidenced learning for the
      integrated sequence. Further, unlike implicit learning for the spatial and object
      sequences, impaired integrated sequence acquisition was specifically related to
      the severity of patients' PD symptomatology. The implicit learning deficits of PD
      patients are discussed with regard to the role played by the basal ganglia in
      integrative sequence learning in the SRT.

PMID- 15964036
TI  - Dyslexia and across-hands finger localization deficits.
AB  - Two experiments on finger localization are reported. Experiment 1 compared
      children who were poor readers with two groups of children matched to poor
      readers for sex and either age (CA controls) or reading age (RA controls). The
      participant's hands were kept out of his or her sight in a semi-open box while
      the fingers of one hand were lightly touched by the experimenter. The
      participant's task was to indicate, using the thumb of either the same hand
      (within-hand condition) or the opposite hand (across-hands condition) to respond,
      the finger(s) which had been touched by the experimenter. Performance was
      significantly impaired in the across-hands condition compared with the within
      hand condition. Experiment 2 was carried out with dyslexic adults and a control
      group of normal readers. Using the same method of responding as in Experiment 1,
      a significant deficit in the across-hands condition compared to the within-hand
      condition was found for both groups. The effect was also obtained for both groups
      when participants were required to point to the relevant fingers on a photograph
      of a hand rather than use the thumb of the opposite hand to respond. The results
      are discussed in relation to the hypothesis of a deficit in inter-hemispheric
      transfer of tactile information in dyslexia.

PMID- 15964037
TI  - Proteome analysis of maize roots reveals that oxidative stress is a main
      contributing factor to plant arsenic toxicity.
AB  - To gain insight into plant responses to arsenic, the effect of arsenic exposure
      on maize (Zea mays L.) root proteome has been examined. Maize seedlings were fed
      hydroponically with 300 microM sodium arsenate or 250 microM sodium arsenite for
      24 h, and changes in differentially displayed proteins were studied by two
      dimensional electrophoresis and digital image analysis. About 10% of total
      detected maize root proteins (67 out of 700) were up- or down-regulated by
      arsenic, among which 20 were selected as being quite reproducibly affected by the
      metalloid. These were analyzed by matrix-assisted laser desorption/ionization
      time of flight mass spectrometry and 11 of them could be identified by comparing
      their peptide mass fingerprints against protein- and expressed sequence tag
      databases. The set of identified maize root proteins highly responsive to arsenic
      exposure included a major and functionally homogeneous group of seven enzymes
      involved in cellular homeostasis for redox perturbation (e.g., three superoxide
      dismutases, two glutathione peroxidases, one peroxiredoxin, and one p
      benzoquinone reductase) besides four additional, functionally heterogeneous,
      proteins (e.g., ATP synthase, succinyl-CoA synthetase, cytochrome P450 and
      guanine nucleotide-binding protein beta subunit). These findings strongly suggest
      that the induction of oxidative stress is a main process underlying arsenic
      toxicity in plants.

PMID- 15964038
TI  - Biosynthesis of pyrethrin I in seedlings of Chrysanthemum cinerariaefolium.
AB  - The biosynthetic pathway to natural pyrethrins in Chrysanthemum cinerariaefolium
      seedlings was studied using [1-13C]d-glucose as a precursor, with pyrethrin I
      isolated using HPLC from a leaf extract. The 13C NMR spectrum of pyrethrin I from
      the precursor-administered seedlings indicated that the acid moiety was
      biosynthesized from d-glucose via 2-C-methyl-d-erythritol 4-phosphate, whereas
      the alcohol moiety was possibly biosynthesized from linolenic acid.

PMID- 15964039
TI  - Rare trisubstituted sesquiterpenes daucanes from the wild Daucus carota.
AB  - Phytochemical and biological investigation of the roots of the wild Daucus carota
      ssp. carota afforded three new and four known compounds, including four
      sesquiterpenes daucane esters (1-3 [new], and 4), one polyacetylene (5), one
      sesquiterpene coumarin (6), and sitosterol glucoside. The structures of the new
      compounds were determined by comprehensive NMR studies, including DEPT, COSY,
      NOESY, HMQC and HMBC analyses. Based on an agar diffusion assay, 1, 2 and 4-6
      were screened and found to contain a range of low antibacterial activities
      against four gram positive (Staphylococcus aureus, Streptomyces scabies, Bacillus
      subtilus, Bacillus cereus) and two gram negative species (Pseudomonas aeruginosa,
      Escherichia coli) as well as antifungal against Fusarium oxysporum and
      Aspergillus niger using cup agar diffusion assay.

PMID- 15964040
TI  - N-Substituted acridone alkaloids from Toddaliopsis bremekampii (Rutaceae:
      Toddalioideae) of south-central Africa.
AB  - Toddaliopsins A-D, four novel 1,2,3-trioxygenated acridone alkaloids, have been
      isolated from the leaves of Toddaliopsis bremekampii. Toddaliopsins B-D are the
      first reported acridone alkaloids with substituted N-methyl groups, in the light
      of which the chemotaxonomic relationship of Toddaliopsis and Vepris is discussed.
      Toddaliopsin C possesses moderate anti-inflammatory activity, which may be
      related to the hydroxy group present at C-1.

PMID- 15964041
TI  - Bibenzyls and dihydroisocoumarins from white salsify (Tragopogon porrifolius
      subsp. porrifolius).
AB  - A phytochemical investigation of three accessions of Tragopogon porrifolius L.
      subsp. porrifolius (Asteraceae, Lactuceae) yielded three new bibenzyl
      derivatives, 5,4'-dihydroxy-3-alpha-l-rhamnopyranosyl-(1-->3)-beta-d
      xylopyranosyloxybibenzyl, 2-carboxyl-3,4'-dihydroxy-5-beta-d
      xylopyranosyloxybibenzyl, tragopogonic acid (2'carboxyl-3',5',4''
      trihydroxyphenylethanone) and three dihydroisocoumarin derivatives, including the
      new natural product 6-O-methylscorzocreticoside I. One of the isolated bibenzyl
      derivatives is considered to be a precursor to the biosynthesis of
      dihydroisocoumarins. Structures of new compounds were established by HR mass
      spectrometry, extensive 1D and 2D NMR spectroscopy, and CD spectroscopy.
      Moreover, radical scavenging activities of the polyphenolic compounds were
      measured using the 2,2-diphenyl-1-picrylhydrazyl assay; two of the bibenzyls
      showed moderate and two of the dihydroisocoumarins showed weak radical scavenging
      activities. The chemosystematic impact of bibenzyls and dihydroisocoumarins is
      discussed briefly.

PMID- 15964042
TI  - Modulation of Leishmania donovani infection and cell viability by testosterone in
      bone marrow-derived macrophages: signaling via surface binding sites.
AB  - Androgens can increase susceptibility toward numerous parasitic infections as
      well as modulate apoptosis of immune cells. According to the current view,
      androgens mediate immune cell activities not only through classical intracellular
      androgen receptors (AR), but also through membrane receptors on the cell surface.
      Here, using murine bone marrow-derived macrophages (BMMs), we examined the
      influence of testosterone on Leishmania donovani infection and cell viability in
      vitro as well as the possible mechanisms. Our data demonstrated that testosterone
      directly increased intramacrophage infection by L. donovani. In addition,
      testosterone decreased cell viability by way of apoptosis, accompanied by
      increased Fas, FasL, and Caspase-8 expression. However, these effects of
      testosterone could not be associated with the classical AR in BMMs since AR was
      not detectable using different experimental techniques. Instead, it was found
      that testosterone could bind to the surface of BMMs by the use of an impermeable
      testosterone-BSA-FITC in confocal laser scanning microscopy and flow cytometry.
      Collectively, our data indicated that the influence of testosterone on L.
      donovani infection and viability of BMMs was mediated through the binding sites
      of testosterone on cell surfaces, which provided a novel mode of direct action of
      testosterone on AR-free BMMs.

PMID- 15964043
TI  - Stimulation of toll-like receptor 2 with bleomycin results in cellular activation
      and secretion of pro-inflammatory cytokines and chemokines.
AB  - The clinical use of bleomycin results in systemic and pulmonary inflammatory
      syndromes that are mediated by the production of cytokines and chemokines. In
      this study, we demonstrate that cell activation is initiated upon the recognition
      of bleomycin as a pathogen-associated molecular pattern by toll-like receptor
      (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high
      levels of TLR2, secretes interleukin (IL)-1beta, IL-8, and tumor necrosis factor
      (TNF)-alpha during bleomycin exposure. The TLR2-dependent nature of cell
      activation and cytokine secretion is supported by (1) the inability of TLR2
      deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa
      B (NF-kappaB) activation and secrete IL-8 in response to bleomycin; (2) the
      acquired ability of HEK293 to exhibit NF-kappaB activation and secrete IL-8 upon
      experimental expression of TLR2; and (3) the inhibition of cell activation in
      TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively,
      these observations identify TLR2 activation as a critical event that triggers NF
      kappaB activation and secretion of cytokines and chemokines during bleomycin
      exposure. Our in vitro findings could serve as a molecular mechanism underlying
      the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin
      engages with other cellular receptors that results in activation of alternate
      signaling pathways and whether the TLR2-agonist activity of bleomycin contribute
      to its anti-neoplastic property deserve further study.

PMID- 15964044
TI  - Ethnobotanical survey of folk toxic plants in southern part of Jordan.
AB  - Thirteen representative phytogeographical sites in the southern part of Jordan
      was surveyed to recognize the folk toxic plant wealth by calculating of FL, RPL,
      and ROP values. One hundred and twenty-five toxic species were recorded in the
      area of study belonging to 56 plant families that were mentioned by three
      informants or more, 53 toxic species (42.4%) were popular, since they were cited
      by more than half of the maximum number of informants which is 30; therefore have
      Rank-Order Priority (ROP) value 50 or more, while 72 species (57.6%) were
      unpopular, since they were cited by less than half of the maximum number of
      informants; therefore have ROP value less than 50. Eighty species (63.5%) have
      known toxicity in neighboring countries while 46 species (36.5%) have not such
      known toxicity. Major toxic effects cited by popular species have exhibited major
      symptoms ranging from skin irritation, gastric and abdominal disturbances,
      abortion, sterility, neuralgic pains including hysteria, and fatigue. The studied
      area has been shown a high level of toxic species diversity, since it is
      dominated by at least four phytogeographical elements, which requires certain
      ecological awareness to protect and reserve the wild and endemic species from
      further threats to enhance the sustainable development.

PMID- 15964045
TI  - Comparative activities of glutathione-S-transferase and dialdehyde reductase
      toward aflatoxin B1 in livers of experimental and farm animals.
AB  - In order to gain a better understanding of the relative activities of glutathione
      S-transferase (GST) and aldehyde reductase toward aflatoxin B1 (AFB1) in relation
      to the variation of species susceptibilities, we studied the in vitro cytosolic
      GST and reductase activities in liver tissues from male Fischer rats, ICR mice
      and golden hamsters, adult male rainbow trouts and female piglets. The GST
      activity was determined by incubating the liver cytosol with glutathione (GSH)
      and AFB1 in the presence of the hamster liver microsomes to metabolize AFB1 to
      AFB1-8, 9-epoxide. The reaction product, AFB1 and GSH conjugate (AFB1-GSH), was
      quantified with HPLC. The reductase activity was determined by incubating liver
      cytosol with AFB1-dialdehyde, followed by the quantification of the metabolic
      product, AFB1-dialcohol, with HPLC. All the animal species possessed the GST
      activities, and AFB1-GSH formed increasingly with the increase of the AFB1
      concentration according to the model of first-order enzyme reaction kinetics. The
      V(max) and K(m) values of the GST activities in rodent species were higher and
      lower, respectively, than those in the trout and pig, being consistent with the
      relative susceptibilities to AFB1 of these animal species. However, no
      relationship was noted between the reductase activity and species susceptibility.
      Thus, the result of this study shows that GST toward AFB1, but not aldehyde
      reductase, is a determinant of the variation of species susceptibilities.

PMID- 15964046
TI  - Activation of human T cell leukemia virus type 1 LTR promoter and cellular
      promoter elements by T cell receptor signaling and HTLV-1 Tax expression.
AB  - Human T cell leukemia virus 1 (HTLV-1) gene expression is regulated by both the
      viral Tax protein and by cellular transcriptional factors. We have previously
      shown that immune activation stimuli such as phorbol esters (PMA) and
      phytohemagglutinin (PHA) cooperate with HTLV-1 Tax expression to enhance HTLV-1
      gene expression in infected T cells through increased activity of the HTLV-1 LTR.
      We now extend these studies to demonstrate roles for the T cell receptor complex,
      Lck, and Ras molecules in the coactivation of the HTLV-1 LTR by Tax and T cell
      activation stimuli. We also observe coactivation of Tax-responsive cellular
      promoter elements containing NF-kappaB and serum response factor (SRF) binding
      sites by Tax and T cell activation stimuli. These results suggest a model whereby
      T cell receptor stimulation and Tax expression coactivate HTLV-1 gene expression
      and cellular gene expression, enhancing activation of latent HTLV-1 and
      expression of cellular genes involved in disease pathogenesis.

PMID- 15964047
TI  - Texture synthesis and perception: using computational models to study texture
      representations in the human visual system.
AB  - Traditionally, texture perception has been studied using artificial textures made
      of random dots or repeated shapes. At the same time, computer algorithms for
      natural texture synthesis have improved dramatically. We seek to unify these two
      fields through a psychophysical assessment of a particular computational model,
      providing insight into which statistics are most vital for natural texture
      perception. We employ Portilla and Simoncelli's texture synthesis algorithm, a
      parametric model that mimics computations carried out in human vision. We find an
      intriguing interaction between texture type (periodic, structured, or 3-D
      textures) and image statistics (autocorrelation function and filter magnitude
      correlations), suggesting different representations may be employed for these
      texture families under pre-attentive viewing.

PMID- 15964048
TI  - RDX and TNT residues from live-fire and blow-in-place detonations.
AB  - Snow was used as a collection medium to examine 1,3,5-hexahydro-1,3,5
      trinitrotriazine (RDX) and 2,4,6-trinitrotoluene (TNT) residues post-detonation
      of 60-, 81-, and 120-mm mortar rounds, 105- and 155-mm howitzer rounds, M67 hand
      grenades, 40-mm rifle grenades, and blocks of C4. Residue-covered snow samples
      were collected, processed, and analyzed for explosives without cross
      contamination from previous detonations and other potential matrix interferences.
      Detonation trials were performed following standard military live-fire and blow
      in-place techniques. When possible, replicate munitions were detonated under
      similar conditions to provide a more reliable estimation of the mass of
      unconsumed high explosive residues. Overall the amount of energetic residues
      deposited from live-fire detonations were considerably less than the energetic
      residues deposited by blow-in-place detonations.

PMID- 15964049
TI  - Human population intake fractions and environmental fate factors of toxic
      pollutants in life cycle impact assessment.
AB  - The present paper outlines an update of the fate and exposure part of the fate,
      exposure and effects model USES-LCA. The new fate and exposure module of USES-LCA
      was applied to calculate human population intake fractions and fate factors of
      the freshwater, marine and terrestrial environment for 3393 substances, including
      neutral organics, dissociating organics and inorganics, emitted to 7 different
      emission compartments. The human population intake fraction is on average 10(-5)
      10(-8) for organics and 10(-3)-10(-4) for inorganics, depending on the emission
      compartment considered. Chemical-specific human population intake fractions can
      be 1-2.7 orders of magnitude higher or lower compared to the typical estimates.
      For inorganics, the human population intake fractions highly depend on the
      assumption that exposure via food products can be modelled with constant
      bioconcentration factors. The environmental fate factor is on average 10(-11)-10(
      18) days m(-3) for organics and 10(-10)-10(-12) days m(-3) for inorganics,
      depending on the receiving environment and the emission compartment considered.
      Chemical-specific environmental fate factors can be 1-8 orders of magnitude
      higher or lower compared to the typical estimates. The largest differences
      between the new and old version of USES-LCA are found for emissions to air and
      soil. This is caused by a significant change in the structure of the air and soil
      compartments in the new version of USES-LCA, i.e. the distinction between rural
      and urban air, including rain-no rain conditions and including soil depth
      dependent intermedia transport.

PMID- 15964050
TI  - Determination of perchlorate in selected surface waters in the Great Lakes Basin
      by HPLC/MS/MS.
AB  - Surface water samples were collected from 55 sites in the Great Lakes Basin and
      analyzed for the presence of perchlorate using HPLC/MS/MS with an isotopically
      enriched internal standard. Sites included areas impacted by heavy industry,
      urbanization, agriculture and atmospheric deposition. Perchlorate was detected at
      several of the sites at concentrations close to the method detection limit (0.2
      microg/l). Despite these low concentrations, its presence was confirmed by sample
      concentration and determination of the isotopic ratio of perchlorate. The
      presence of perchlorate at two of the sites was related to a fireworks display
      which had occurred prior to sampling. The other detections of perchlorate were in
      rivers/creeks draining watersheds which had high density livestock and crop
      farming activity. We suspect the two are related. To our knowledge, these are the
      first reported concentrations of perchlorate in Canadian surface waters.

PMID- 15964051
TI  - Distribution characteristics of polychlorinated biphenyls in crucian carp
      (Carassius auratus) from major rivers in Korea.
AB  - Polychlorinated biphenyls (PCBs) levels in crucian carp were determined at 20
      locations along four major river systems, several small-scale rivers and a
      wetland in Korea. Twenty-eight congeners, ranging from tri- to hepta-CBs were
      detected. A gas chromatograph with a mass selective detector was used to quantify
      the individual PCB congeners. The objectives of this study were to investigate
      the levels of contamination of PCBs in freshwater fish and to observe the pattern
      of their distribution. The sampling locations were chosen among 31 sampling sites
      that are currently used as environmental residue checkpoints by the Korean
      Ministry of Environment. Concentrations of individual congeners ranged from not
      detectable (n.d.) to 0.75 ng g(-1) on a wet weight basis. The total
      concentrations of PCBs at each site ranged from n.d. to 5.41 ng g(-1) of wet
      weight. The most heavily contaminated site was the Nakdong estuary located near
      the Shinpyung-Janglim factory district. The PCB 153 and 138 were the principal
      congeners and penta- and hexa-chlorinated biphenyls comprised the main congener
      groups.

PMID- 15964052
TI  - Concentrations of PCBs, organochlorine pesticides and heavy metals (lead,
      cadmium, and copper) in fish from the Drome river: potential effects on otters
      (Lutra lutra).
AB  - In this study samples of ten species of fish were analyzed for concentrations of
      organochlorine pesticides, PCBs and heavy metals (Pb, Cd, and Cu). Fish were
      captured using electric fishing on ten sites along the Drome river (Rhone-Alpes
      region). Quantitative determination of the organochlorine and PCBs compounds was
      performed by gas chromatography-electron-capture detection (GC-ECD). The
      concentrations of heavy metals were determined by atomic absorption
      spectrophotometry. Samples contained detectable concentrations of lindane, PCBs,
      and heavy metals but at concentrations below the maximum residue limit (MRL). Non
      parametric statistical analysis was performed to distinguish groups of sites with
      different levels of contamination. PCBs concentrations increased along the river
      with four groups of sites significantly different from each other. Cadmium
      concentrations were below the MRL. Lead contamination showed two groups
      significantly different and a repartition similar to PCBs. Copper contamination
      was correlated with the localization of vineyards. We assessed the potential
      effects of contamination the otter (Lutra lutra). The concentrations of all
      pollutants analyzed in fish sampled in this study are lower than the threshold
      values described in literature. The Drome river is relatively unpolluted river,
      and the establishment of otter populations should not be affected by pollution.

PMID- 15964053
TI  - HCHs and DDTs in salt marsh plants (Scirpus) from the Yangtze estuary and nearby
      coastal areas, China.
AB  - HCHs and DDTs in salt marsh plants taken from intertidal flats in the Yangtze
      estuary and coastal area in April and July 2002 were determined by GC-ECD. A
      significant seasonal effect was observed for HCHs and DDTs in sources and
      concentration levels in different sample types including above-ground tissues and
      roots as well as the whole plants and rhizospheric sediments. The results
      indicated that the concentration of t-HCH was higher in the above-ground tissues
      than in their roots in April; however, the partitioning of DDTs between
      contaminated sediments and the roots showed the higher concentrations of t-DDT in
      their roots. HCHs and DDTs concentration levels were higher in above-ground
      tissues than in roots in July. BCFs of HCHs and DDTs exhibited lower values with
      higher levels of contaminants in sediments, and higher values with lower levels
      in sediments.

PMID- 15964054
TI  - Emissions from an automobile fire.
AB  - The emissions from automobile fires have been investigated. The main gas phase
      components were analysed in small-scale tests with representative material from
      an automobile. A more detailed investigation of full-scale simulated automobile
      fires was also conducted, including the characterisation of gas phase components,
      particulates and run-off water from extinguishing activities. Three separate full
      scale fire tests have been characterised: a fire ignited and developed in the
      engine compartment; a fire ignited inside the coupe, that was extinguished in the
      early stages; and a similar fire ignited inside the coupe that was allowed to
      spread until the entire vehicle was involved in the fire. The quantitative
      analysis of the smoke gases from the full-scale fires showed that emissions with
      a potentially negative impact on the environment, or chronic toxic effect on
      humans, were produced in significant quantities. These emissions included HCl,
      SO2, VOCs (e.g. benzene), PAHs, and PCDDs/PCDFs. Analysis of run-off water
      indicated that it was severely contaminated, containing elevated levels of both
      organic compounds and metals. Comparison with data from other vehicle fires found
      in the literature shows that contamination by lead, copper, zinc, and antimony
      appears to be significant in water run-off from these types of fires.

PMID- 15964055
TI  - Dry deposition of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)
      in ambient air.
AB  - The PCDD/Fs in the ambient air associated with concentration and dry deposition
      flux of four seasons were characterized in rural area. The mean PCDD/F
      concentrations were 0.342, 0.221, 0.675, 0.741 pg m(-3) and the mean I-TEQ values
      were 0.027, 0.016, 0.024, 0.063 pg m(-3) in spring, summer, fall and winter,
      respectively. Ambient air in winter was higher by a factor of 3.4 and 3.9 for
      PCDD/F concentration and I-TEQ, respectively, than in summer. The study area is
      located in a Tropical region. Hence, domestic heating is not found in this area
      and is not responsible for the elevated winter concentration in comparison to
      other studies. A smooth plate with a sharp leading edge that is pointed into the
      wind by a wind vane was used for measuring dry deposition flux of PCDD/Fs.
      Atmospheric dry deposition fluxes of total PCDD/Fs were 140, 116, 137, and 207 pg
      m(-2)day(-1) in spring, summer, fall, and winter, respectively, and averaged
      approximately 150 pg m(-2)day(-1). The total dry deposition flux was found to
      decrease as the temperature increased. Calculated dry deposition velocities of
      total PCDD/Fs were 0.45, 0.52, 0.32 and 0.39 cm s(-1) in spring, summer, fall,
      and winter, respectively, and averaged 0.42 cm s(-1).

PMID- 15964056
TI  - A spatial temporal assessment of pollution from PCBs in China.
AB  - This research represents an assessment of the current state of pollution from
      polychlorinated biphenyls (PCBs) in China. Various environmental media including
      sediment, water, organism and soil were analyzed and the spatial character of PCB
      pollution in each environmental medium was determined. On a national basis, PCB
      levels in all environmental media were relatively low, with little evidence of
      major contamination in China's main regions and rivers. However, there were some
      locations with high PCB concentrations. Sediments in Pearl River (83.1 ng/g) and
      its estuary (58.9 ng/g), Dalian Bay (58.1 ng/g) and Songhua River (36.8 ng/g) had
      relatively high level of PCBs. There were also some areas, which were mainly the
      industrial pollution sites or PCB equipment storage locations, remained seriously
      polluted with the highest PCB residue level of 150,000 ng/g. In addition,
      Minjiang Estuary (985.2 ng/g) and Taihu Lake (631 ng/g) had high levels of water
      pollution, while Pearl Estuary (635.7 ng/g) and Jiaozhou Bay (273.3 ng/g) had
      relatively high PCB levels in organisms. PCB pollution in soil was limited to a
      few special pollution areas with the highest PCB level of 4.5448 x 10(6) ng/g.
      Point source pollution was the common pattern of contamination, influenced
      primarily by local geographic, economic and historical factors. Analysis of PCB
      concentrations from the 1980s to 1990s shows an increasing trend, possibly due to
      the improper disposal of and leakage from PCB containers, chemical transfers, and
      the general rise of industrial pollution.

PMID- 15964057
TI  - Seasonal evolution of gas-phase PCB concentrations in the Venice Lagoon area.
AB  - The concentrations of gas-phase PCBs were measured from March 2002 to June 2003
      at two sites of the Venice Lagoon and at one site of the Euganei hills. The aims
      of this study were to evaluate the various gas-phase PCB sources, the spatial and
      temporal variability of PCB concentrations in the gas-phase that enter the Venice
      Lagoon atmosphere and the influence of the air temperature on PCB trends. The
      highest annual average concentration of summation PCBs was observed at the
      station directly influenced by "urban" sources with values about 3 and 1.5 times
      higher compared to the concentrations found at the stations where "marine"
      sources and "not subjected to direct local sources" were respectively sampled
      from. The temporal trends of summation PCBs concentrations were similar at the
      three sampling stations corresponding to seasonal temperature changes. Greater
      concentrations occurred in the summer and first autumn months while the lower
      ones occurred in late autumn and winter. The temperature dependences were
      investigated using plots of the natural logarithm of the summation PCBs
      concentrations vs. reciprocal mean temperatures.

PMID- 15964058
TI  - The role of bio-mechanical treatments of waste in the dioxin emission
      inventories.
AB  - PCDD/Fs are one of the most studied molecules in the world because of their
      toxicity. In the last years the toxicity of these compounds has been analyzed in
      details. For years PCDD/F inventories have pointed out the significant role of
      municipal solid waste (MSW) incinerators in the overall balance. Recently, thanks
      to new regulations on PCDD/F emissions, in a few countries this scenario is
      changing: it can be demonstrated that modern MSW incinerators can play a
      secondary role even if the percentage of MSW sent to combustion has increased. In
      the latest inventories an unconventional source of PCDD/F has appeared: in
      nineties some biogas characterizations have demonstrated that there is a release
      of PCDD/F from MSW sanitary landfills. In addition, the combustion of collected
      biogas can generate not negligible amounts of PCDD/F. A new question can be put:
      does the MSW contribute with other management options to the overall balance of
      PCDD/F? The present work points out that a detailed inventory should take into
      account also the PCDD/F release from bio-mechanical treatment plants (both
      composting and bio-drying/bio-stabilization plants). However the contribution
      from this option is secondary when it is compared with the one from old MSW
      incinerators.

PMID- 15964059
TI  - Phytoextraction of lead from firing range soil by Vetiver grass.
AB  - Phytoextraction techniques utilizing a sterile strain of Vetiver grass (Vetiveria
      zizanoides) along with soil amendments were evaluated for removing lead and other
      elements such as Zn, Cu, and Fe from the soil of a 50-year old active firing
      range at the Savannah River Site (SRS). Lead-contaminated soil (300-4500 ppm/kg)
      was collected, dried, placed in pots, fertilized, and used as a medium for
      growing transplanted Vetiver grass plants in a greenhouse. The uptake of metals
      by the plants was evaluated in response to various fertilization and pre-harvest
      treatment schemes. Baseline metal concentrations in the soil of all pots were
      measured prior to planting and when the plants were harvested. Plants grew better
      when fertilized with Osmocote fertilizer in comparison to plants fertilized with
      10-10-10 (NPK) fertilizer. Application of a chelating agent, EDTA, one week prior
      to harvest significantly increased the amount of lead that was phytoextracted.
      Lead concentrations of up to 1390-1450 ppm/kg in tissue samples were detected.
      Maximum Pb levels were observed in root tissues. The addition of non-lethal doses
      of a slow-release herbicide in combination with EDTA did not appear to further
      enhance phytoextraction or the translocation of Pb into shoots. The study
      indicated that the use of Vetiver grass coupled with the use of chelating soil
      amendments has considerable potential for use as a remedial strategy for lead
      contaminated soils such as those associated with firing ranges.

PMID- 15964060
TI  - The Sirt1 deacetylase modulates the insulin-like growth factor signaling pathway
      in mammals.
AB  - The lifespan of the nematode, Caenorhabditis elegans, can be extended by
      mutations affecting components of the insulin-like growth factor (IGF) signaling
      cascade or by overexpression of SIR2, an NAD+-dependent protein deacetylase. The
      mammalian homologue of SIR2, Sirt1, has been shown to modulate the activity of
      FoxO, a transcription factor that is downstream of the IGF signaling system.
      These results suggest that Sirt1 ought to affect the IGF pathway. We report here
      evidence that this is the case in mice. The loss of Sirt1 protein in mice results
      in increased expression of the IGF binding protein IGFBP1, a secreted modulator
      of IGF function. A number of the anatomical characteristics of Sirt1-null mice
      closely resemble those of transgenic mice overexpressing IGFBP1. Our data suggest
      that Sirt1 is part of a regulatory loop that limits the production of IGFBP1
      thereby modulating IGF signaling.

PMID- 15964061
TI  - Oxidative stress effects fibrinolytic system in dialysis uraemic patients.
AB  - INTRODUCTION: Enhanced oxidative stress (SOX) and changes in the fibrinolytic
      system are common in end-stage renal failure patients undergoing maintenance
      dialysis. This study attempted to verify the existence of a relationship between
      SOX documented by Cu/Zn superoxide dismutase (Cu/Zn SOD) and fibrinolysis
      analyzed by tissue-type plasminogen activator (tPA), urokinase-type plasminogen
      activator (uPA), plasminogen activator inhibitor 1 (PAI-1) and
      plasmin/antiplasmin (PAP) complexes in dialysis patients. MATERIALS AND METHODS:
      Twenty-seven patients on maintenance haemodialysis (HD) and 16 on maintenance
      peritoneal dialysis (CAPD) were examined together with 18 healthy controls. Pre
      dialysis blood levels of all the parameters were determined using commercially
      ELISA kits. RESULTS: Cu/Zn SOD, uPA and PAP levels were increased in both groups
      of dialyzed patients compared to the controls. PAI-1 was significantly lower in
      CAPD subjects compared to HD subjects and control group. PAI-1/uPA ratio and PAI
      1/tPA ratio were significantly decreased in CAPD and HD compared to controls,
      being significantly lower in CAPD patients relative to HD patients. In the
      patients, increased Cu/Zn SOD levels directly correlated with those of uPA
      (r=0.565, p<0.0001) and PAP (r=0.335, p<0.05); the fibrinolytic markers were also
      positively associated with each other (r=0.377, p<0.05). CONCLUSIONS: The
      positive association between Cu/Zn SOD and both uPA as well as PAP levels
      suggests a link between SOX and the fibrinolytic activity in dialysis patients.
      We hypothesize that increased SOX-mediated fibrinolytic activity may be a part of
      the counter-system against activation of blood coagulation in these patients.

PMID- 15964062
TI  - Papillary serous carcinoma--a less radio-sensitive subtype of endometrial cancer.
AB  - OBJECTIVE: To explore factors that determine the response of endometrial cancer
      to radiation therapy. Such factors may influence treatment outcome and yield
      predictive information about individual patients and their tumors. METHODS: A
      retrospective study of the complete pathologic response (pCR) rates in the
      hysterectomy specimens of patients, who had undergone pre-operative radiotherapy
      for > or = Stage II biopsy-proven endometrial carcinoma, was performed. 62
      patient records were reviewed with respect to patient characteristics, tumor
      stage, histological grade and subtype, radiation technique and dose, and presence
      or absence of pCR in the post-operative hysterectomy specimen. RESULTS: 24 of 62
      specimens exhibited a pCR. The only significant factor with respect to pCR was
      presence of uterine papillary serous carcinoma (UPSC). None of the seven cases of
      UPSC displayed a pCR (P = 0.036 Fischer's exact test), despite not differing from
      the non-UPSC cases in any other tumor, treatment, or patient factors. No factors
      were found that separated non-UPSC cases with a pCR from those without.
      CONCLUSIONS: These data suggest an intrinsic radioresistance within UPSC, which
      may have implications for future treatment strategies. UPSC has documented
      genetic aberrations that may account for this, although its true radiosensitivity
      has yet to be quantitated directly. Future studies should focus on the molecular
      basis of its response to radiation. The reasons for the heterogeneous response of
      non-UPSC has yet to be elucidated and should also be investigated.

PMID- 15964063
TI  - Fertility-sparing surgery for ovarian low malignant potential tumors.
AB  - OBJECTIVE: Ovarian low malignant potential (LMP) tumors have an excellent
      prognosis when treated by surgical resection. Conservative management usually
      involves leaving behind the uterus and contralateral adnexa to allow future
      childbearing. The purpose of this study was to determine the outcome of women
      treated with fertility-sparing surgery. METHODS: All patients diagnosed with
      ovarian LMP tumors between 1984 and 2003 were identified at three institutions.
      Data were retrospectively extracted from clinical records. RESULTS: Thirty-eight
      (15%) of 249 women with LMP tumors underwent fertility-sparing surgery. Twenty
      three were nulliparous and four primiparous. Thirty-three (87%) underwent
      unilateral salpingo-ophorectomy and five (13%) cystectomy. Fourteen patients also
      had contralateral cystectomy or biopsy. Thirty-four (89%) were stage I, one (3%)
      stage II and three (8%) stage III. Most tumors had serous (55%) or mucinous (42%)
      histology. No patients received adjuvant therapy. Six (16%) of 38 recurred after
      a median follow-up of 26 months: five in the remaining ovary were salvaged with
      surgical resection alone, and none died from recurrent LMP tumor. Five women
      delivered six term infants during post-treatment surveillance. CONCLUSION:
      Fertility-sparing surgery for ovarian LMP tumors is an option for motivated
      patients. Preservation of the contralateral adnexa increases the risk of
      recurrence, but surgical resection is usually curative.

PMID- 15964064
TI  - Update on reproductive biotechnologies in small ruminants and camelids.
AB  - Recent advances in reproductive biotechnologies in small ruminants include
      improvement of methods for in vitro production of embryos and attempts at
      spermatogonial stem cell transplantation. In vitro production of embryos by
      IVM/IVF, intra-cytoplasmic sperm injection (ICSI), or nuclear transfer (NT) has
      been made possible by improvements in oocyte collection and maturation
      techniques, and early embryo culture systems. However, in vitro embryo production
      still is not very efficient due to several limiting factors affecting the outcome
      of each step of the process. This paper discusses factors affecting in vitro
      embryo production in small ruminants and camelids, as well as preliminary results
      with the technique of spermatogonial stem cell transplantation.

PMID- 15964065
TI  - Evaluation of boar sperm maturation after co-incubation with caput, corpus and
      cauda epididymal cultures [corrected].
AB  - Boar sperm from the proximal caput epididymis were co-incubated with 1, 4, 7, 10
      and 14-day old caput, corpus and cauda epididymal cultures for 24, 48 and 72 h.
      Boar kidney epithelial cells (LLC-PK1) and ECM alone were used as negative
      controls. Sperm motility, morphology and membrane integrity were studied to
      evaluate boar sperm maturation in vitro. Our results showed that epithelial cell
      monolayers (10, 14-day old) create a suitable microenvironment for the survival
      of proximal caput sperm and the maintenance of sperm motility over a 72 h period.
      Moreover, corpus epididymal tubule fragments in culture (1, 4-day old) are
      capable of promoting the migration of the cytoplasmic droplet along the sperm
      tail after 24h of co-incubation.

PMID- 15964066
TI  - Thermoelectroelastic solutions for surface bone remodeling under axial and
      transverse loads.
AB  - Theoretical prediction of surface bone remodeling in the diaphysis of the long
      bone under various external loads are made within the framework of adaptive
      elastic theory. These loads include external lateral pressure, electric and
      thermal loads. Two solutions are presented for analyzing thermoelectroelastic
      problems of surface bone remodeling. The analytical solution that gives explicit
      formulation is capable of modeling homogeneous bone materials, while the semi
      analytical solution is suitable for analyzing inhomogeneous cases. Numerical
      results are presented to verify the proposed formulation and to show the effects
      of mechanical, thermal and electric loads on surface bone remodeling process.

PMID- 15964067
TI  - The effect of the addition of a polyglutamate motif to RGD on peptide tethering
      to hydroxyapatite and the promotion of mesenchymal stem cell adhesion.
AB  - Mimicking endogenous bone-binding proteins, RGD peptides have been synthesized
      with polyacidic amino acid domains in order to ionically tether the peptides to
      bone-like synthetic biomaterials, including hydroxyapatite (HA). However, a
      direct comparison of unmodified RGD with polyacidic-conjugated RGD has not been
      performed, and thus a benefit for the acidic domain has not been established. We
      evaluated the peptide/HA bond of RGD peptides with and without an attached
      polyglutamate sequence (E(7)), as well as examined mesenchymal stem cell (MSC)
      adhesion and morphology as they were affected by the conjugated peptide. We found
      that significantly more E(7)RGD was bound to HA than RGD at all coating
      concentrations tested, and moreover, more E(7)RGD was retained on the HA surface
      even after extended washing in serum-free media. Consistent with in vitro
      results, higher levels of E(7)RGD than RGD remained on HA that had been implanted
      in vivo for 24 h, indicating that the polyacidic domain improved peptide-binding
      efficiency. At several peptide concentrations, E(7)RGD increased cell adhesion
      compared to RGD surfaces, establishing a biological benefit for the E(7)
      modification. In addition, HA pre-coated sequentially with low-density E(7)RGD (1
      10 microg/ml) and serum (FBS) stimulated cell adhesion and spreading, compared to
      either coating alone, suggesting that an ionic linkage allows for the potential
      adsorption of serum proteins to unoccupied sites, which may be important for bone
      formation in vivo. Collectively, these results suggest that tethering peptides to
      HA via a polyglutamate domain is an effective method for improving the peptide/HA
      bond, as well as for enhancing MSC adhesion.

PMID- 15964068
TI  - Sustained remission including marked regression of a paravertebral plasmacytoma
      in a patient with heavily pretreated, relapsed multiple myeloma after treatment
      with bortezomib.
AB  - Despite advances in systemic and supportive therapies, multiple myeloma (MM) has
      remained an incurable disease, which underlines the need for novel approaches to
      therapy. Recent data indicate that the proteasome-inhibitor bortezomib has marked
      activity with manageable toxicity in relapsed and refractory MM. We here report
      on a patient suffering from heavily pretreated and refractory MM with a
      paravertebral tumor manifestation. After three cycles of bortezomib, the patient
      achieved near-complete remission, as well as a nearly complete regression of the
      paravertebral tumor. This case further documents that bortezomib is an effective
      novel therapy for MM.

PMID- 15964069
TI  - Acute monocytic leukemia and multiple abnormalities in a child with duplication
      of 1q detected by GTG-banding and SKY.
AB  - Patients with 1q duplication have demonstrated a wide range of multiple
      congenital abnormalities. Alterations involving this chromosomal region have
      being described in hematopoietic malignancies and a series of candidate genes
      that may be associated with neoplasias have been mapped in this region. We
      describe a case of partial trisomy 1q "syndrome" and acute monocytic leukemia.
      Cytogenetic study of the bone marrow cells by GTG-banding and spectral
      karyotyping (SKY) showed dup(1)(q23q44) in all cells analyzed. The
      dismorphological features with the dup(1q) suggest a constitutional chromosome
      alteration and the first, in our knowledge, association of a trisomy 1q
      "syndrome" with AML.

PMID- 15964070
TI  - Binding of porcine ficolin-alpha to lipopolysaccharides from Gram-negative
      bacteria and lipoteichoic acids from Gram-positive bacteria.
AB  - Protein(s) reactive with N-acetyl-D-glucosamine (GlcNAc) was isolated from
      porcine nonimmune serum. The molecular weight of the purified protein was found
      to be mainly 40 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      under reducing conditions. The N-terminal 10 amino acid sequence of the purified
      protein were found to be identical to that of porcine ficolin-alpha reported
      previously. In enzyme-linked immunosorbent assay, the purified protein was found
      to react with lipopolysaccharides (LPS) from different Gram-negative bacteria
      such as Esherichia coli, Salmonella typhimurium, Salmonella enteritidis,
      Salmonella abortus equi, Pseudomonas aeruginosa, Shigella flexeneri, and Serratia
      marcescens and with lipoteichoic acid (LTA) from Gram-positive bacteria such as
      Streptococcus sanguis, Bacillus subtilis, Streptococcus pyogenes, and
      Staphylococcus aureus. The purified protein also reacted with E. coli O26
      isolated from food poisoning and bovine feces and heat-treated Gram-positive
      bacteria such as S. aureus, B. cereus, B. subtilis, Enterococcus faecium, and
      Corynebacterum bovis. On the other hand, porcine IgG isolated from nonimmune
      serum showed different reactivity with these LPS, LTA, and heat-treated bacterial
      cells. From the present findings, purified porcine serum protein reactive with
      GlcNAc is concluded to be ficolin-alpha playing an important role(s) in innate
      immunity against microbial infection with Gram-positive and -negative bacteria.

PMID- 15964071
TI  - Benzoic acid transformation via conjugation with peptides and final fate of
      conjugates in higher plants.
AB  - Transformation of [1(14)C]- and [7(14)C] benzoic acids in sterile seedlings of
      maize (Zea mays) and pea (Pisum sativum) was studied. The tested labeled
      compounds were supplied in plants through roots as water solutions. The larger
      part of the assimilated benzoic acid forms conjugates with low-molecular-weight
      plant peptides. As a result of hydrolytic cleavage of the conjugation products,
      initial labeled benzoic acid molecules and unlabeled amino acids are released. It
      is supposed that conjugation takes place between the benzoic acid carboxyl group
      and the peptide functional groups. The amino acid composition of the conjugate
      peptides was determined. After removal of the plants from the labeled benzoic
      acids-containing medium, the amount of conjugation products gradually decreases
      and the process is accompanied by the emission of labeled carbon dioxide,
      indicating that the conjugation products are degraded and that their radioactive
      component carbon atoms are then oxidized to carbon dioxide. Parallel to the
      conjugation reaction, a smaller part of the benzoic acid that entered the plant
      is transformed via oxidation, as a result of which an aromatic ring is cleaved
      and the resulting aliphatic fragment is incorporated into regular cell
      metabolism. The smallest part of the assimilated benzoic acid radiolabel is
      incorporated into a cell biopolymer fraction. Benzoic acid, of which the
      radioactive label is detected in the plant subcellular organelles and finally
      deposited in the vacuoles, affects the cell ultrastructural organization and the
      activities of the main metabolic enzymes. Intensification of catabolic processes
      takes place, indicating an energy demand needed for xenobiotic detoxification.

PMID- 15964072
TI  - Anthropogenic impacts on the distribution and biodiversity of benthic
      macroinvertebrates and water quality of the Langat River, Peninsular Malaysia.
AB  - A study of the impacts of anthropogenic activities on the distribution and
      biodiversity of benthic macroinvertebrates and water quality of the Langat River
      (Peninsular Malaysia) was conducted. Four pristine stations from the upstream and
      4 stations at the downstream receiving anthropogenic impacts were selected along
      the river. For 4 consecutive months (March-June 1999), based on the Malaysian DOE
      (Malaysia Environmental Quality Report 2000, Department of Environment, Ministry
      of Science, Technology and Environment Malaysia. Maskha Sdn. Bhd. Kuala Lumpur,
      86pp; Malaysia Environmental Quality Report 2001, Department of Environment,
      Ministry of Science, Technology and the Environment Malaysia) water quality index
      classes, the upstream stations recorded significantly (P<0.05) higher Biological
      Monitoring Working Party scores and better water quality indices than those of
      the downstream. The total number of macrobenthic taxa and their overall richness
      indices and diversity indices were significantly (P<0.05) higher at the upstream
      stations (54 taxa) than at the downstream stations (5 taxa). The upstream of the
      Langat River was dominated by Ephemeroptera and chironomid dipterans while other
      orders found in small quantities included Trichoptera, Diptera, Plecoptera,
      Odonata, Ephemeraptera, Coleoptera, and Gastropoda. On the other hand, the
      downstream of the river was mainly inhabited by the resistant Oligochaeta worms
      Limnodrilus spp. and Branchiodrilus sp. and Hirudinea in small numbers. The
      relationships between the physicochemical and the macrobenthic data were
      investigated by Pearson correlation analysis and multiple stepwise regression
      analysis. These statistical analyses showed that the richness and diversity
      indices were generally influenced by the total suspended solids and the
      conductivity of the river water. This study also highlighted the impacts of
      anthropogenic land-based activities such as urban runoff on the distribution and
      species diversity of macrobenthic invertebrates in the downstream of the Langat
      River. The data obtained in this study supported the use of the bioindicator
      concept for Malaysian rivers. Some sensitive (Trichopteran caddisflies and
      Ephemeraptera) and resistant species (Oligochaeta such as Limnodrilus spp.) are
      identified as potential bioindicators of clean and polluted river ecosystems,
      respectively, for Malaysian rivers.

PMID- 15964073
TI  - Nicotine use in schizophrenia: the self medication hypotheses.
AB  - The behavioural and cognitive effects of nicotine in schizophrenia have received
      much interest in recent years. The rate of smoking in patients with schizophrenia
      is estimated to be two- to four-fold the rate seen in the general population.
      Furthermore such patients favour stronger cigarettes and may also extract more
      nicotine from their cigarettes than other smokers. The question has been raised
      whether the widespread smoking behaviour seen in this patient group is in fact a
      manifestation of a common underlying physiology, and that these patients smoke in
      an attempt to self-medicate. We present an overview of the explanations for
      elevated rates of smoking in schizophrenia, with particular emphasis on the
      theories relating this behaviour to sensory gating and cognitive deficits in this
      disorder that have been viewed as major support for the self-medication
      hypotheses.

PMID- 15964074
TI  - The development of a cognitive model of schizophrenia: placing it in context.
AB  - This review provides a historical perspective on a model for schizophrenia based
      on results of experiments derived from learning theory. It was developed by the
      author in collaboration with Jeffrey Gray and numerous colleagues, (e.g. [Gray,
      J.A., McNaughton, N., 2000. The Neuropsychology of Anxiety. second ed. Oxford
      University Press, Oxford; Hemsley, D.R., 1987a An experimental psychological
      model for schizophrenia. In: Hafner, H., Gattaz, W.F., Janzarik, W. (Eds.),
      Search for the Causes of Schizophrenia, vol. 1. Springer, New York, pp. 179-188.;
      Hemsley, D.R., 1993. A simple (or simplistic?) cognitive model for schizophrenia.
      Behaviour Research and Therapy 31, 633-646]. It contrasts with earlier cognitive
      formulations [e.g. Hemsley, D.R., 1975. A two stage model of attention in
      schizophrenia research. British Journal of Social and Clinical Psychology 14, 81
      88], which emphasised a weakening of contextually elicited response biases, and
      lacked a link to potential neural bases of the disorder. The model emphasizes the
      need to demonstrate patterns of performance that are not interpretable in terms
      of the well established 'generalized deficit' manifest in schizophrenia. It
      proposes that the cognitive disturbance is a change in the way stored material is
      integrated with sensory input and ongoing motor programmes. In particular,
      spatial and temporal context fail to activate appropriate stored regularities. A
      number of possible pathways from the cognitive disturbance to the symptoms of
      schizophrenia are outlined; again the term 'context' is widely employed. Thus, it
      has been invoked to explain the occurrence of hallucinations, delusions, thought
      disorder and disruptions in the sense of personal identity. However the term
      'context' is ill-defined and the review indicates the variety of ways in which it
      may exert its influence. These are unlikely to reflect the operation of a unitary
      mechanism.

PMID- 15964075
TI  - Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia.
AB  - Epidemiological studies have indicated an association between maternal bacterial
      and viral infections during pregnancy and the higher incidence of schizophrenia
      in the resultant offspring post-puberty. One hypothesis asserts that the reported
      epidemiological link is mediated by prenatal activation of the foetal immune
      system in response to the elevation of maternal cytokine level due to infection.
      Here, we report that pregnant mouse dams receiving a single exposure to the
      cytokine-releasing agent, polyriboinosinic-polyribocytidilic acid (PolyI:C; at
      2.5, 5.0, or 10.0 mg/kg) on gestation day 9 produced offspring that subsequently
      exhibited multiple schizophrenia-related behavioural deficits in adulthood, in
      comparison to offspring from vehicle injected or non-injected control dams. The
      efficacy of the PolyI:C challenge to induce cytokine responses in naive non
      pregnant adult female mice and in foetal brain tissue when injected to pregnant
      mice were further ascertained in separate subjects: (i) a dose-dependent
      elevation of interleukin-10 was detected in the adult female mice at 1 and 6h
      post-injection, (ii) 12 h following prenatal PolyI:C challenge, the foetal levels
      of interleukin-1beta were elevated. The spectrum of abnormalities included
      impairments in exploratory behaviour, prepulse inhibition, latent inhibition, the
      US-pre-exposure effect, spatial working memory; and enhancement in the locomotor
      response to systemic amphetamine (2.5 mg/kg, i.p.) as well as in discrimination
      reversal learning. The neuropsychological parallels between prenatal PolyI:C
      treatment in mice and psychosis in humans, demonstrated here, leads us to
      conclude that prenatal PolyI:C treatment represents one of the most powerful
      environmental-developmental models of schizophrenia to date. The uniqueness of
      this model lies in its epidemiological and immunological relevance. It is, sui
      generis, ideally suited for the investigation of the neuropsychoimmunological
      mechanisms implicated in the developmental aetiology and disease processes of
      schizophrenia.

PMID- 15964076
TI  - Increased association of CD38 with lipid rafts in T cells from patients with
      systemic lupus erythematosus and in activated normal T cells.
AB  - In this study we have determined whether there is a relationship between CD38
      expression on T cells, its distribution in different membrane microdomains, and T
      cell activation in SLE patients. The data show that CD38 expression is augmented
      in ex vivo CD3+, CD4+, CD8+, and CD25+ SLE T cells, which correlates with its
      increased insolubility in Brij 98 detergent, and its translocation into lipid
      rafts. Moreover, SLE T cells show an altered CD4:CD8 ratio, which is due to a
      decreased proportion of CD4+ T cells and a concomitant increase in the proportion
      of CD8+ T cells. These data are consistent with the increased CD38 expression and
      lipid raft formation, and the significant reduction in the CD4:CD8 ratio observed
      in mitogen-stimulated normal T cells as compared with that in ex vivo untouched
      normal T cells. Increased expression of CD38 in floating rafts from SLE T cells,
      or from activated normal T cells may modulate TCR signaling by providing or
      sequestering signaling molecules to the engaged TCR.

PMID- 15964077
TI  - Vanadium (V) peroxocomplexes: structure, chemistry and biological implications.
AB  - A short account on the identification in solution of diverse type of vanadium
      peroxocomplexes is offered. The methodology used is a combination of several
      techniques, i.e., multinuclear NMR spectroscopy, electrospray ionization mass
      spectrometry (ESI-MS) and theoretical calculation. The analysis has been carried
      out in aqueous alcoholic solutions, and in some case also in the presence of
      appropriate ligands, in order to model some of the natural conditions where
      vanadium-dependent haloperoxidase enzymes (VHPO) work. With the results obtained,
      it has been possible to shed light on important aspects of the catalytic cycle of
      VHPO. Furthermore, a number of synthetic aspects of the reactivity of the various
      vanadium peroxocomplexes is reviewed.

PMID- 15964078
TI  - Procedure for minimizing stress for fMRI studies in conscious rats.
AB  - Functional magnetic resonance imaging (fMRI) in conscious animals is evolving as
      a critical tool for neuroscientists. The present study explored the effectiveness
      of an acclimation procedure in minimizing the stress experienced by the animal as
      assessed by alterations in physiological parameters including heart rate,
      respiratory rate, and serum corticosterone levels. Results confirm that as the
      stress of the protocol is minimized, there is a significant decrease in head
      movements and enhancement in data quality. The feasibility of improving the
      quality of fMRI data acquired in alert rats by utilizing a relatively simple
      technique is presented.

PMID- 15964080
TI  - Mitek QuickAnchor fixation of cochlear implants using a minimal access technique.
AB  - RATIONALE: In children with thick cortical bone, surgical exposure for cochlear
      implant fixation is difficult when using a minimal access technique. We report
      our experience in these children using the Mitek QuickAnchor system. METHODS: A
      retrospective review of all children undergoing cochlear implantation over a 12
      month period was performed to identify those children in which a Mitek
      QuickAnchor was used. Measurements of cortical bone thickness at the receiver
      stimulator well site were obtained from pre-operative CT scans of temporal bones
      of all children. The application of the Mitek QuickAnchor system was also
      reviewed. RESULTS: Cochlear implant fixation using the Mitek QuickAnchor system
      was performed in 14 children (mean age 12 years) during the study period. The
      mean cortical bone thickness was 5.6mm in patients receiving the Mitek
      QuickAnchor system and 3.2mm in patients undergoing conventional fixation. The
      difference in cortical thickness was highly statistically significant. Successful
      secure fixation was obtained in all cases. CONCLUSIONS: The Mitek QuickAnchor
      system provides an effective method of cochlear implant fixation when using a
      minimal access technique in children with thick cortical bone.

PMID- 15964079
TI  - Prenatal exposure to the acetylcholinesterase inhibitor methanesulfonyl fluoride
      alters forebrain morphology and gene expression.
AB  - Methanesulfonyl fluoride (MSF) is a CNS-selective acetylcholinesterase (AChE)
      inhibitor, currently being developed and tested for the treatment of symptoms of
      Alzheimer's disease. We have previously confirmed that a single in utero exposure
      to MSF at clinically appropriate doses inhibits AChE activity in fetal rat brain
      by 20%, and when administered throughout gestation, MSF achieves a 40% level of
      inhibition. Here, we show that rats chronically exposed in utero to MSF display
      marked sex-specific differences in morphological development of the cerebral
      cortical layers compared with controls at 7 days of age. Forebrain size and
      cortical thickness were increased in females and decreased in males. An analysis
      of gene expression in neonate brain on the day of birth revealed sex-specific
      differential expression of over 25 genes, including choline acetyltransferase
      (ChAT), which were affected by prenatal MSF exposure. Many of these genes are
      associated with sexual differentiation and brain development, while others are
      involved in more generalized cellular and metabolic processes. The changes
      observed in cortical morphology and gene expression suggest a critical
      developmental role for AChE in the fetal nervous system, most likely through its
      effect on cholinergic neurotransmission.

PMID- 15964081
TI  - Conversion disorder in a child presenting as sudden sensorineural hearing loss.
AB  - Pseudohypoacacusis is a form of conversion disorder in which a hearing loss is
      found in the absence of organic disease. A case of an 11-year-old boy with
      auditory conversion disorder after mild head trauma is reported. The child
      presented with unilateral hearing loss, with no accompanying vestibular symptoms
      and no history of otologic disease. Auditory testing revealed severe right-sided
      sensorineural hearing loss, however, CT scan was normal. There was a family
      history of conversion disorder and the child was undergoing an emotionally
      stressful period. It was decided to treat the child conservatively with close
      monitoring and a repeat audiogram 2 weeks later. One week after presentation, the
      child's hearing suddenly returned to normal after a second very minor head
      injury. It is important to consider pseudohypoacusis or conversion disorder even
      in cases such as trauma, when the clinical history supports a diagnosis of
      hearing loss.

PMID- 15964082
TI  - Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan
      Hospital and the 309th Hospital.
AB  - The transmission of severe acute respiratory syndrome-associated coronavirus
      (SARS-CoV) is associated with close contact to SARS patients and droplet
      secretions of those patients. The finding of positive RT-PCR results from stools
      of SARS patients suggests that stools of SARS patients or sewage containing
      stools of patients could transmit SARS-CoV. We used a novel style of
      electropositive filter media particle to concentrate the SARS-CoV from the sewage
      of two hospitals receiving SARS patients in Beijing. We also used cell culture,
      RT-PCR and gene sequencing to detect and identify the viruses from sewage. No
      infectious SARS-CoV contamination was found in any of the samples collected, but
      the nucleic acid of SARS-CoV could be detected in the sewage from the two
      hospitals before disinfection. While the RNA was only detected in three samples
      from the 309th Hospital, the others were negative after disinfection. These
      findings provide strong evidence that SARS-CoV can be excreted through the
      stool/urine of patients into sewage system, thus making the sewage system a
      possible route of transmission.

PMID- 15964083
TI  - Cloning and functional characterization of NtCPK4, a new tobacco calcium
      dependent protein kinase.
AB  - A cDNA clone, encoding calcium (Ca2+)-dependent protein kinase (CDPK or CPK), was
      isolated from tobacco (Nicotiana tabacum). The full-length cDNA of 2360 bp
      contains an open reading frame for NtCPK4 consisting of 572 amino acid residues.
      Sequence alignment indicated that NtCPK4 shared high similarities with other CPKs
      and some CPK-related protein kinases (CRKs). Biochemical analyses showed that
      NtCPK4 phosphorylated itself and calf thymus histones fraction III-S (histone III
      S) in a calcium-dependent manner, and the K0.5 of calcium activation was 0.29
      microM or 0.25 microM with histone III-S or syntide-2 as substrates,
      respectively. The Vmax and Km were 588 nmol min-1 mg-1 and 176 microg ml-1,
      respectively, when histone III-S was used as substrate, while they were 2415 nmol
      min-1 mg-1 and 58 microM, respectively, with syntide-2 as substrate. In addition,
      the phosphorylation of NtCPK4 occurred on threonine residue, as shown by
      capillary electrophoresis analyses. All of these data demonstrated that NtCPK4
      was a serine/threonine protein kinase. NtCPK4 as a low copy gene was expressed in
      all tested organs including the root, leaf, stem, and flower of tobacco, while
      its expression was temporally and spatially modulated in both productive and
      vegetative tissues during tobacco growth and development. NtCPK4 expression was
      also increased in response to the treatment of gibberellin or NaCl. Our study
      suggested that NtCPK4 might play vital roles in plant development and responses
      to environmental stimuli.

PMID- 15964084
TI  - Incidence of anemia in older Koreans: community-based cohort study.
AB  - Most epidemiologic data are related to the prevalence of anemia, and there is
      little information regarding the incidence or etiology of newly diagnosed anemia
      in older people. The purpose of this study was to define the incidence and
      characteristics of anemia in the elderly population of Korea. Three hundred
      thirty-two independent, community-living, elderly persons aged 60 years and older
      were enrolled, and laboratory tests including iron profiles were performed. The
      mean age was 72+/-4.8 years and the mean hemoglobin was 13.4+/-1.1g/dl. During
      the follow-up period of 3 years, 24 subjects (3 males and 21 females) were newly
      diagnosed with anemia, which led to a 3-year incidence of 7.2% (24/332). Among
      the 24 subjects with new-onset anemia, iron deficiency anemia (IDA) was diagnosed
      in 5 subjects, while anemia of chronic disease (ACD) was detected in 8 subjects.
      Underlying illnesses were diabetes mellitus, osteoarthritis, renal insufficiency,
      hypothyroidism and malignancy. In those subjects with new-onset anemia, the serum
      iron, ferritin, transferrin saturation and albumin were lower than in the normal
      group. In conclusion, the 3-year incidence of anemia among Korean elderly people
      was determined to be 7.2%, and ACD was the most commonly defined cause of anemia.

PMID- 15964085
TI  - Aneurysm of saphenous vein graft causing anterior myocardial infarction by
      possibly compressing left internal mammary artery.

PMID- 15964086
TI  - Acute myocarditis associated with cardiac amyloidosis manifesting as transient
      complete atrioventricular block and slow ventricular tachycardia.
AB  - This is the first report of conduction system disturbances and slow ventricular
      tachycardia (VT), related to acute myocarditis associated with cardiac
      amyloidosis. A 57-year-old female was presented with chest pain and pre-syncope
      after flu-like symptoms, and was promptly diagnosed with acute myocarditis. The
      initial electrocardiogram (ECG) revealed complete atrioventricular (AV) block,
      and transient slow VT was observed after an atropine injection (0.5 mg). This AV
      conduction disturbance persisted for 12 days, and spontaneously resolved. Left
      ventricular function was relatively well preserved, and an endomyocardial biopsy
      revealed acute myocardial inflammation and underlying amyloid deposits. A His
      bundle recording, taken 6 weeks after the initial manifestation, indicated normal
      AV nodal conduction. Endomyocardial biopsies have proven helpful with regard to
      the diagnosis of acute myocarditis superimposed on amyloidosis, in patients who
      present with conduction disorder and relatively preserved ventricular function,
      as was seen in this case.

PMID- 15964087
TI  - Risk stratification for arrhythmic death after myocardial infarction: current
      perspective and future direction.
AB  - The number of patients eligible for implantable cardioverter defibrillator
      implantation is large and growing. Results of the Multicenter Automatic
      Defibrillator Implantation Trial-II, Comparison of Medical Therapy, Pacing, and
      Defibrillation in Heart Failure trial, and Sudden Cardiac Death in Heart Failure
      Trial will have a major impact on health care expenditure and economics in all
      countries. Therefore, one of the most important challenges in today's cardiology
      is finding more specific and accurate risk stratification strategies (rather than
      simply ejection fraction) for primary prevention of sudden cardiac death in
      patients who have suffered myocardial infarction. We hereby reviewed the existing
      data on potential risk stratifiers and assessed their impact on every day
      decision making and patient selection for ICD implantation.

PMID- 15964088
TI  - Prior blunt chest trauma may be a cause of single vessel coronary disease;
      hypothesis and review.
AB  - Prompted by a case where a patient (with no risk factors, and single vessel
      disease) developed angina pectoris after previous blunt chest trauma, we searched
      Medline for blunt chest trauma and myocardial ischaemia. We found 77 cases
      describing AMI after blunt chest trauma, but only one reporting angina pectoris.
      We focused on the age and sex distribution, type of trauma, the angiography
      findings and the time interval between the trauma and the angiography. The age
      distribution was atypical, compared to AMI in general; 82% of the patients with
      AMI after blunt chest trauma were less than 45 years old, and only 2.5% more than
      60 years old. The most common trauma was a road traffic accident, and the LAD was
      the vessel most often affected. Angiography revealed 12 cases with completely
      normal vessels, which might be due to spasm or recanalisation; 31 cases showed
      occlusion but no atherosclerosis, which strongly suggested a causal relation
      between the trauma and subsequent occlusion. AMI should therefore be considered
      in patients suffering from chest pain after blunt chest trauma. Because traumatic
      AMI might often be the result of an intimal tear or dissection, thrombolytic
      therapy might worsen the situation and acute PCI must be considered preferable.
      It seems likely that lesser damage could lead to longer-term stenosis we suspect
      that this sequence is grossly under-reported. This could have medico-legal
      implications.

PMID- 15964089
TI  - Herd-level factors associated with isolation of Salmonella in a multi-state study
      of conventional and organic dairy farms I. Salmonella shedding in cows.
AB  - The objective of this study was to evaluate associations between herd
      characteristics and the isolation of Salmonella from dairy cows in Minnesota,
      Wisconsin, Michigan, and New York. Study farms were 129 conventional and organic
      farms enrolled without regard to previous history of Salmonella infection. Herds
      were sampled at 2-month intervals over a 1-year period. This is the largest study
      to date on Salmonella shedding in dairy cows and the only study evaluating herd
      level risk factors using longitudinal sampling to characterize Salmonella
      shedding on dairy farms. Salmonella was isolated in fecal samples from 1026
      (4.9%) of 20,089 cows. Over the course of the study, 113 (87.6%) of 129 farms had
      at least one positive cow sample. Multi-variable logistic regression using the
      generalized estimating equations approach was used to test the association
      between herd-level risk factors and the dependent variable of within-herd
      prevalence by visit (number of Salmonella-positive cows/number of cows sampled)
      after adjustment for effects of herd size, season, state of origin, and the
      multiple sampling occasions per herd. Factors retained in the final model
      included lack of use of tiestall or stanchion facilities to house lactating cows
      (OR=1.9; 95% CI: 1.1-3.3), not storing all purchased concentrate or protein feeds
      in an enclosed building (OR=2.5; 95% CI: 1.3-4.9), not using monensin in weaned
      calf or bred heifer diets (OR=3.2; 95% CI: 2.0-5.4), access of lactating or dry
      cows to surface water (e.g., lake, pond, river, or stream) (OR=2.3; 95% CI: 1.3
      3.9), disposal of manure in liquid form (slurry or irrigation, as opposed to
      disposal of manure by broadcast/solid spreader only) on owned or rented land
      (OR=1.8; 95% CI: 1.3-3.9), and cows eating or grazing of roughage from fields
      where manure was applied in solid or liquid form and not plowed under during the
      same growing season (OR=1.8; 95% CI: 1.0-3.0). A seasonal association was also
      present as cows were more likely to be Salmonella-positive in summer, spring, and
      fall compared to winter. Herd size was not associated with Salmonella shedding in
      the final multi-variable model. The herd-level risk factors identified in this
      study could potentially be implemented in Salmonella control programs on dairy
      farms.

PMID- 15964090
TI  - Having the wrong friends? Peer effects in adolescent substance use.
AB  - Swedish cross-sectional survey data on young individuals aged 12-18-year-old was
      used to analyse school-class based peer effects in binge drinking, smoking and
      illicit-drug use. Significant and positive peer effects were found for all three
      activities. By introducing school/grade fixed effects, the estimated peer effects
      were identified by variation in peer behaviour across school-classes within
      schools and grades, implying that estimates were not biased due to endogenous
      sorting of students across schools. Further, endogeneity bias due to bi
      directionality of peer effects was found for binge drinking and smoking.
      Controlling for this source of endogeneity resulted in even stronger peer
      effects.

PMID- 15964091
TI  - Cytolytic replication of coxsackievirus B2 in CAR-deficient rhabdomyosarcoma
      cells.
AB  - The six coxsackievirus B serotypes (CVB1-6) use the coxsackie- and adenovirus
      receptor (CAR) for host cell entry. Four of these serotypes, CVB1, 3, 5 and 6,
      have also shown the capacity to replicate and cause cytolysis in rhabdomyosarcoma
      (RD) cells, a CAR-deficient cell line. This extended tropism has been associated
      with an acquired ability to bind decay accelerating factor (DAF). In this study,
      we have adapted the CVB2 prototype strain Ohio-1 (CVB2/O) to replicate in RD
      cells. Two types of infection were identified: (I) an enterovirus-typical, lytic
      infection, and (II) a non-lytic infection. Both CVB2/O-RD variants retained the
      prototype-ability to cause cytopathic effect in HeLa cells using CAR as receptor.
      Phenotypic and genotypic changes in the CVB2/O-RD-variants were determined and
      compared to the prototype cultured in HeLa cells. Inhibition studies using
      antibodies against CAR and DAF revealed a maintained ability of the CVB2/O-RD
      variants to bind CAR, but no binding to DAF was observed. In addition, neither
      the prototype nor the CVB2/O-RD-variants were able to cause hemagglutination in
      human red blood cells, an enterovirus feature associated with affinity for DAF.
      Sequence analysis of the CVB2/O-RD-variants showed acquired mutations in the
      capsid region, suggesting extended receptor usage towards an alternative, yet
      unidentified, receptor for CVB2.

PMID- 15964092
TI  - Genomic features of lactic acid bacteria effecting bioprocessing and health.
AB  - The lactic acid bacteria are a functionally related group of organisms known
      primarily for their bioprocessing roles in food and beverages. More recently,
      selected members of the lactic acid bacteria have been implicated in a number of
      probiotic roles that impact general health and well-being. Genomic analyses of
      multiple members of the lactic acid bacteria, at the genus, species, and strain
      level, have now elucidated many genetic features that direct their fermentative
      and probiotic roles. This information is providing an important platform for
      understanding core mechanisms that control and regulate bacterial growth,
      survival, signaling, and fermentative processes and, in some cases, potentially
      underlying probiotic activities within complex microbial and host ecosystems.

PMID- 15964093
TI  - Viral kinetics in patients with lamivudine-resistant hepatitis B during adefovir
      lamivudine combination therapy.
AB  - BACKGROUND/AIMS: Mathematical analysis of viral kinetics during lamivudine
      adefovir combination therapy has not yet been performed in patients with
      lamivudine-resistant hepatitis B. METHODS: In 8 patients with lamivudine
      resistant hepatitis B, adefovir dipivoxil (10 mg/day) was added to ongoing
      lamivudine. Viral decay during the first 8 weeks of combination therapy was
      described by a biphasic model to determine the efficacy: epsilon, of blocking
      viral production, the clearance: c, of free virus, and the loss of infected
      cells: delta. RESULTS: Median epsilon was 98%, median c was 0.7/day, and median
      delta was 0.07/day. No significant association was found between viral kinetic
      and baseline parameters and virologic and biochemical treatment response. When
      compared with viral kinetic constants reported for higher dose adefovir dipivoxil
      monotherapy, epsilon was lower (P=0.026) and delta was higher (P=0.008) in this
      study whereas c did not differ between both studies. CONCLUSIONS: Although a
      recent study did not show any differences in the reduction of HBV DNA comparing
      monotherapy with adefovir dipivoxil to adefovir-lamivudine combination therapy in
      patients with lamivudine-resistant chronic hepatitis B, mathematical analysis of
      early viral kinetics suggests an additional effect of lamivudine on the infected
      cell loss during adefovir-lamivudine combination therapy.

PMID- 15964094
TI  - Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor
      deficient mice.
AB  - BACKGROUND/AIMS: Pharmacological blockade of the renin-angiotensin system (RAS)
      attenuates liver fibrogenesis in rats. Here, we provide genetic evidence
      implicating angiotensin type 1 (AT1) receptors in liver fibrogenesis. METHODS:
      Wild type (WT) and AT1a knockout [AT1a (-/-)] mice were subjected to either sham
      operation or bile-duct ligation. Fibrosis was assessed by Sirius Red staining and
      hydroxyproline hepatic content. Fibrogenic and inflammatory cytokines were
      measured by ELISA. RESULTS: Bile duct ligation-induced elevation of serum liver
      enzymes was similar in WT and AT1a (-/-) mice. Bile duct ligated WT mice showed
      inflammatory changes and severe septal fibrosis. In contrast, AT1a (-/-) mice
      showed minor fibrotic lesions. Collagen accumulation was lower in AT1a (-/-) mice
      compared to WT mice. The increase in hepatic concentration of TGFbeta1 and pro
      inflammatory cytokines was attenuated in AT1a (-/-) mice compared to WT mice.
      Immunohistochemistry analysis revealed decreased infiltration by inflammatory
      cells, lipid peroxidation products as well as decreased phosphorylation of c-Jun
      and p42/44 MAPK in AT1a (-/-) mice compared to AT1 (+/+) mice. CONCLUSIONS: AT1
      receptors play an important role in the development of fibrosis. Pharmacological
      blockade of AT1 receptors appears to be a promising approach to treat liver
      fibrosis.

PMID- 15964095
TI  - Genomic and functional characterization of stellate cells isolated from human
      cirrhotic livers.
AB  - BACKGROUND/AIMS: Hepatic stellate cells (HSCs) are believed to participate in
      liver fibrogenesis and portal hypertension. Knowledge on human HSCs is based on
      studies using HSCs isolated from normal livers. We investigated the phenotypic,
      genomic and functional characteristics of HSCs from human cirrhotic livers.
      METHODS: HSC were obtained from normal and cirrhotic human livers. Cells were
      characterized by immunocytochemistry and gene microarray analysis. Cell
      proliferation, Ca(2+) changes and cell contraction were assessed by 3H-thymidine
      incorporation and by using an epifluorescence microscope. RESULTS: HSCs freshly
      isolated from human cirrhotic livers showed phenotypical features of
      myofibroblasts. These features were absent in HSCs freshly isolated from normal
      human livers and become prominent after prolonged culture. HSCs from cirrhotic
      human livers markedly express genes involved in fibrogensis, inflammation and
      apoptosis. HSCs from normal livers after prolonged culture preferntially
      expressed genes related to fibrogenesis and contractility. Agonists induced
      proliferation, Ca(2+) increase and cell contraction in HSCs isolated from human
      cirrhotic livers. Response to agonists was more marked in culture-activated HSCs
      and was not observed in HSCs freshly isolated from normal livers. CONCLUSIONS:
      HSCs from human cirrhotic livers show fibrogenic and contractile features.
      However, the current model of HSCs activated in culture does not exactly
      reproduce the activated phenotype found in cirrhotic human livers.

PMID- 15964096
TI  - Altered expression of MAP-2, GAP-43, and synaptophysin in the hippocampus of rats
      with chronic cerebral hypoperfusion correlates with cognitive impairment.
AB  - Chronic cerebral hypoperfusion causes cognitive impairment, but the underlying
      molecular mechanism is not well understood. We used permanent occlusion of
      bilateral common carotid arteries (2-VO) to induce chronic cerebral hypoperfusion
      in male Wistar rats. Cognitive impairment and the expression patterns of MAP-2,
      GAP-43, and synaptophysin were examined. We found that both learning capacity and
      memory were gradually impaired in the rats with chronic cerebral hypoperfusion
      concomitant with increased duration of 2-VO treatment. Four weeks of 2-VO
      treatment resulted in down-regulation of synaptophysin expression at the protein
      levels, and a further decrease was observed at 10-20 weeks, although mRNA levels
      remained the same. Ten weeks of 2-VO treatment lead to down-regulation of MAP-2
      expression at both the mRNA and protein levels with a further decrease at 20
      weeks. Interestingly, GAP-43 mRNA was significantly up-regulated by 2-VO
      treatment, although the protein levels were not altered. Therefore, the cognitive
      impairment caused by chronic cerebral hypoperfusion may be partially explained by
      reduced expression of synaptophysin and MAP-2 at the protein level. The reduction
      in MAP-2 expression may be attributed to the inhibition of transcription, while
      the reduction in synaptophysin expression might be due to the inhibition of
      translation. Up-regulation of GAP-43 mRNA in the rat hippocampus with 2-VO
      treatment suggests that a compensatory mechanism may antagonize ischemic
      challenges.

PMID- 15964097
TI  - RNAi-mediated silencing of leptin gene expression increases cell death in C6
      glioblastoma cells.
AB  - We previously demonstrated that the brain, pituitary, and C6 glioblastoma cells
      express leptin. To determine the physiological role of brain-derived leptin, we
      sought to selectively silence its expression using RNA interference (RNAi) in
      vitro. One of four potential targets, siRNA L7, reduced leptin mRNA by 50% (P <
      0.05) and protein by 55% (P < 0.0001) in C6 cells. RNAi also induced a twofold
      increase in cell death as seen by ethidium homodimer-1 (P < 0.015) and TUNEL (P <
      0.005) staining. These data suggest that endogenous leptin may be a critical
      factor promoting cell survival in the brain.

PMID- 15964098
TI  - Bacterial resistance to antibiotics: modified target sites.
AB  - Alteration in the target sites of antibiotics is a common mechanism of
      resistance. Examples of clinical strains showing resistance can be found for
      every class of antibiotic, regardless of the mechanism of action. Target site
      changes often result from spontaneous mutation of a bacterial gene on the
      chromosome and selection in the presence of the antibiotic. Examples include
      mutations in RNA polymerase and DNA gyrase, resulting in resistance to the
      rifamycins and quinolones, respectively. In other cases, acquisition of
      resistance may involve transfer of resistance genes from other organisms by some
      form of genetic exchange (conjugation, transduction, or transformation). Examples
      of these mechanisms include acquisition of the mecA genes encoding methicillin
      resistance in Staphylococcus aureus and the various van genes in enterococci
      encoding resistance to glycopeptides.

PMID- 15964099
TI  - Hypothalamic rAAV-mediated GDNF gene delivery ameliorates age-related obesity.
AB  - Intraventricular delivery of glial cell line-derived neurotrophic factor (GDNF)
      results in weight loss. We hypothesized that this effect of GDNF was likely
      mediated via its effects on dopaminergic neurons in the hypothalamus. Continuous
      rAAV-mediated GDNF expression in the hypothalamus of young and senescent rats
      resulted in weight loss compared to controls. However, GDNF-induced weight loss
      was unrelated to alterations in hypothalamic dopamine levels. The weight loss was
      associated with decreased food intake and increased energy expenditure, but these
      effects were not mediated by changes in hypothalamic NPY or POMC expression.
      Moreover, uncoupling protein 1 levels were unchanged in brown adipose tissue
      (BAT). The reduction in weight and adiposity were as great or greater in the aged
      rats even though aged rats are generally resistant to weight loss therapies. In
      summary, central GDNF gene delivery reduces weight and adiposity in young and
      aged rats through decreased food intake and increased energy expenditure. Our
      observations in aged rats suggest that GDNF may be especially effective in
      reducing obesity in aged obese rats.

PMID- 15964100
TI  - Effects of intranasal insulin on cognition in memory-impaired older adults:
      modulation by APOE genotype.
AB  - Raising insulin acutely in the periphery and in brain improves verbal memory.
      Intranasal insulin administration, which raises insulin acutely in the CNS
      without raising plasma insulin levels, provides an opportunity to determine
      whether these effects are mediated by central insulin or peripheral processes.
      Based on prior research with intravenous insulin, we predicted that the treatment
      response would differ between subjects with (epsilon4+) and without (epsilon4-)
      the APOE-epsilon4 allele. On separate mornings, 26 memory-impaired subjects (13
      with early Alzheimer's disease and 13 with amnestic mild cognitive impairment)
      and 35 normal controls each underwent three intranasal treatment conditions
      consisting of saline (placebo) or insulin (20 or 40 IU). Cognition was tested 15
      min post-treatment, and blood was acquired at baseline and 45 min after
      treatment. Intranasal insulin treatment did not change plasma insulin or glucose
      levels. Insulin treatment facilitated recall on two measures of verbal memory in
      memory-impaired epsilon4- adults. These effects were stronger for memory-impaired
      epsilon4- subjects than for memory-impaired epsilon4+ subjects and normal adults.
      Unexpectedly, memory-impaired epsilon4+ subjects showed poorer recall following
      insulin administration on one test of memory. These findings suggest that
      intranasal insulin administration may have therapeutic benefit without the risk
      of peripheral hypoglycemia and provide further evidence for apolipoprotein E
      (APOE) related differences in insulin metabolism.

PMID- 15964101
TI  - Dysmorphology and microstructural degradation of the corpus callosum: Interaction
      of age and alcoholism.
AB  - Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing
      prevalence in the older population. Alcoholism is a source of substantial
      deterioration in brain tissue and has been consistently observed in vivo and
      postmortem in white matter. To quantify the potential compounded effect of age
      and alcoholism, we used conventional structural MRI and diffusion tensor imaging
      (DTI) to examine the macrostructural and microstructural integrity of the corpus
      callosum, one of the most prominent white matter structures of the brain, in 131
      adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and
      17 alcoholic women, who were abstinent from alcohol for an average of 3 months,
      showed similar patterns and extents of callosal shrinkage, which was greatest in
      the genu and body and less prominent in the splenium. Microstructural integrity
      was measured with DTI as fractional anisotropy, an index of intravoxel
      orientational coherence of white matter fibers, and bulk mean diffusivity, an
      index of the amount of intravoxel water motility. The macrostructural shrinkage
      was accompanied by abnormalities in anisotropy and diffusivity of the
      microstructural environment of these callosal regions, indicative of disruption
      of structural constituents of local brain white matter. Correlational analyses
      revealed an age-alcohol interaction, where older alcoholics had smaller genu and
      splenium and higher diffusivity in these regions than younger alcoholics.
      Significant correlations between regional MRI and DTI measures and performance on
      working memory, visuospatial ability, and gait and balance provided evidence for
      the functional ramifications of the callosal abnormalities in the alcoholics.
      Thus, despite abstinence from alcohol, the interaction of age and recent
      alcoholism history exerted a compounded untoward effect on callosal
      macrostructure and microstructure.

PMID- 15964102
TI  - Progenitor cells from the adult mouse brain acquire a neuronal phenotype in
      response to beta-amyloid.
AB  - Neurospheres from adult mouse subventricular zone (SVZ) were grown in suspension
      cultures for 12-15 days. Neurospheres consisted mainly of neural precursor cells
      (NPCs) immunoreactive for nestin and also contained nestin-negative precursors.
      We used these neurospheres to determine the effects of synthetic beta-amyloid
      fragments (both betaAP(1-42) and betaAP(25-35)) on NPC proliferation,
      differentiation and survival. We show that neurospheres exposed to 25 microM
      betaAP(25-35) or betaAP(1-42) for 24 h (a toxic condition for mature neurons) did
      not undergo apoptosis. Instead, betaAP(25-35) orientated nestin-negative
      precursors towards nestin-positive NPCs and turned nestin-positive NPCs into
      neuroblasts. Intracerebroventricular infusion of full-length betaAP(1-42)
      increased the population of PSA-NCAM-positive cells in the SVZ, without affecting
      proliferation. We conclude that betaAP influences the fate of progenitor cells,
      driving their differentiation towards a neuronal lineage.

PMID- 15964103
TI  - Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates
      developed by reverse genetics containing L polymerase protein mutations imported
      from heterologous paramyxoviruses.
AB  - Live-attenuated recombinant human parainfluenza virus type 2 (rHPIV2) vaccine
      candidates were created using reverse genetics by importing known attenuating
      mutations in the L polymerase protein from heterologous paramyxoviruses into the
      homologous sites of the HPIV2 L protein. Four recombinants (rF460L, rY948H,
      rL1566I, and rS1724I) were recovered and three were attenuated for replication in
      hamsters. The genetic stability of the imported mutations at three of the four
      sites was enhanced by use of alternative codons or by deletion of a pair of amino
      acids. rHPIV2s bearing these modified mutations exhibited enhanced attenuation.
      The genetically stabilized mutations conferring a high level of attenuation will
      be useful in generating a live-attenuated virus vaccine for HPIV2.

PMID- 15964104
TI  - The changing epidemiology of chickenpox in Alberta.
AB  - BACKGROUND: Varicella vaccine was licensed in Canada in 1998. The province of
      Alberta introduced a universal publicly funded varicella vaccination program in
      2001. PURPOSE: To describe the epidemiology of non-fatal cases of chickenpox for
      which publicly funded health services were utilized for the period 1986-2002.
      METHODS: We used the records of Alberta's universal, publicly funded health care
      insurance system to identify cases of chickenpox for the period 1986-2002. The
      earliest dated utilization of a health service for which there was an ICD9-CM
      code of 052.xx or an IC10-CA code of B01.xx was used as the date of illness
      onset. Denominators for rates were estimated using mid-year population estimates
      from the Alberta Health Care Insurance Registry. Age-specific rates were
      estimated for each year. RESULTS: The crude incidence of chickenpox significantly
      declined over the period 1994-2002, most steeply after the year 2000. The
      incidence of chickenpox varied by age group and year and there was evidence of
      age-group-year interaction. Among those aged 5-19 years, chickenpox incidence
      began to decline prior to vaccine licensure in Canada. Among those aged less than
      one year and those aged 1-4 years, the incidence increased until 1999 when a
      decline began. Over the period 0.8% of cases were hospitalized. CONCLUSION:
      Chickenpox rates began to decline prior to the introduction of the publicly
      funded vaccination program; however the declines in rates among the youngest age
      groups are consistent with a vaccination program effect.

PMID- 15964105
TI  - Development of a synthetic consensus sequence scrambled antigen HIV-1 vaccine
      designed for global use.
AB  - Induction of high levels of broadly reactive cytotoxic T lymphocytes (CTL)
      remains a promising approach for an effective HIV-1 vaccine. We have developed a
      novel genetic-based vaccine strategy that encodes consensus overlapping peptide
      sets from all HIV-1 proteins scrambled together. This synthetic scrambled antigen
      vaccine (SAVINE) strategy has significant advantages, e.g. capacity to encode
      more antigens safely and is very flexible compared to traditional isolate-based
      strategies. The SAVINE vaccine strategy is clearly immunogenic, being able to
      restimulate a range of human HIV-1 specific responses in vitro and induce HIV-1
      specific immunity in vivo in mice. Interestingly, different in vivo delivery
      strategies affected the resulting immunity and immunodominance pattern in mice.
      This platform strategy could be used for other infections and cancers where T
      cell responses are important for protection.

PMID- 15964106
TI  - Laugier-Hunziker syndrome: a rare cause of mucocutaneous pigmentation.
AB  - An 80-year-old white woman presented with brown pigmentation on both sides of the
      buccal mucosa and lower lip and patchy freckling in her nails, which was
      diagnosed as Laugier-Hunziker syndrome.

PMID- 15964107
TI  - 'Double barrel' 2.0mm mini-plates to fix fractures of the neck of the mandibular
      condyle.

PMID- 15964108
TI  - Interesting case: Metastatic adrenal adenocarcinoma of the mandible.

PMID- 15964109
TI  - Design and performance of a bioreactor system for mechanically promoted three
      dimensional tissue engineering.
AB  - There is currently considerable interest in increasing the response of
      mesenchymal cells to physical forces, and numerous loading devices have been used
      to increase the formation of skeletal tissue in vivo and in vitro. We have
      developed a bioreactor system to apply cyclic strains on three-dimensional
      specimens over a range of 0-20,000 mustrain. The piezoelectric-driven mechanism
      allows the precise adjustment and control over load-related deformations of
      tissue, as shown by finite-element calculations of deformation of a collagen gel
      under load. We present the design of the bioreactor and its performance in
      specimens of tissue containing activated osteoblasts and chondrocytes. Biaxial
      tissue straining at 2,000 mustrain led to a substantial increase in the number of
      both types of cell compared with unstimulated controls. The synthesis of cell
      specific extracellular matrix proteins increased when physiological loads (2,000
      mustrain) were applied in the bioreactor, whereas higher deformations (20,000
      mustrain) resulted in a reduction in proliferation and differentiation of cells.
      The mechanisms whereby mechanical stimulation leads to a defined cell reaction
      are not known, but the application of physiological micromovements in
      extracorporeal tissue chambers is a promising approach to the formation of hard
      tissue.

PMID- 15964110
TI  - Interesting case: An unusual case of keloid scarring.

PMID- 15964111
TI  - Digital infestation with the human bot fly.
AB  - We report a finger infestation by the human bot fly, Dermatobia hominis, describe
      the biology and life cycle of the fly and review the diagnosis and treatment of
      the condition.

PMID- 15964112
TI  - The impact of the CCD-angle on range of motion and cup positioning in total hip
      arthroplasty.
AB  - BACKGROUND: Biomechanical analysis and clinical experience reveal that offset
      total hip stems increase soft tissue tension and reduce the risk for dislocation
      in total hip arthroplasty. Most of these stems have a smaller neck-shaft-angle to
      increase the offset. This study investigates if changing the neck-shaft-angle has
      an impact on how cup and stem should be positioned with regard to range of
      motion. METHODS: A mathematical model of a total hip arthroplasty was developed
      to analyze range of motion until impingement between cup and neck. Range of
      motion was determined for each combination of neck-shaft-angles and additional
      parameters like cup inclination, cup anteversion, stem antetorsion, head/neck
      ratio and design of the cup opening. RESULTS: A maximized range of motion is
      achieved for neck-shaft-angles between 125 degrees and 131 degrees . Reducing the
      neck-shaft-angle by one degree requires reducing the cup anteversion by about 2
      degrees and increasing the cup inclination by 0.45 degrees . Stems with neck
      shaft-angles more than 135 degrees are not recommended when the head/neck ratio
      is 2.3 or less. INTERPRETATION: Stems with a reduced neck-shaft-angle for an
      increased offset should be coupled with cups that are inclined slightly higher
      and less anteverted as compared to a standard stem. Precise recommendations for
      optimal component positioning can only be given for a specific prosthesis system
      regarding all parameters.

PMID- 15964113
TI  - Congenital cervical block vertebrae are associated with caudally adjacent discs.
AB  - BACKGROUND: Knowledge on the time course of changes in cervical disc height and
      cervical kinematics at motion segments adjacent to congenital block vertebrae is
      fragmentary. Compared with this, after surgical fusion of cervical spine segments
      some find increased degenerative processes in combination with hypermobility or
      instability while others were unable to confirm these changes. This cross
      sectional study was undertaken to investigate whether congenital block vertebrae
      are associated with an increased risk of disc degeneration and hypermobility at
      adjacent motion segments. METHODS: In 25 subjects (mean age 40 years) disc
      height, vertebral height and segmental mobility at motion segments adjacent to a
      congenital block vertebra were assessed quantitatively by distortion-compensated
      Roentgen analysis. The findings were compared to a normal database. FINDINGS:
      Height of the disc cranially adjacent to the block vertebra did not deviate from
      the norm while height of the caudally adjacent disc was significantly reduced.
      The height of the vertebrae adjacent to the block did not deviate from normal.
      The motion segments formed by the block vertebra and the adjacent discs and
      vertebrae exhibited no deviation from normal with respect to sagittal plane
      rotational or translational motion. INTERPRETATION: Congenital block vertebrae do
      not result in rotational or translational hyper- or hypomobility at motion
      segments adjacent to the block. Whether the observed, significant height
      reduction of the caudally adjacent disc is caused by degeneration following the
      block formation cannot undoubtedly be concluded as the initial state is not
      known. Further longitudinal studies are needed to investigate this issue.

PMID- 15964114
TI  - Quantitative assessment of the velocity-dependent increase in resistance to
      passive stretch in spastic plantarflexors.
AB  - BACKGROUND: Although numerous studies revealed that isokinetic dynamometers were
      valuable tools for assessing spastic hypertonia, no standard methodology using
      such devices is currently widespread in clinical setting. The aim of this study
      was to standardize a protocol to assess spastic hypertonia in the triceps surae.
      METHODS: The passive resistance during dorsiflexions imposed from 10 to 300
      degrees /s with an isokinetic dynamometer was measured at the neutral position in
      15 patients with spastic hypertonia and 12 healthy subjects. The normalized
      passive resistance was obtained by expressing raw passive resistance as a percent
      of the values measured at the lowest velocity (10 degrees /s). EMG signals from
      plantar and dorsiflexors were also recorded. FINDINGS: While no significant
      difference between spastic patients and control subjects was observed in raw
      passive resistance values, the difference was significant for each tested
      velocity when considering the normalized values. Furthermore, the Ashworth score
      was significantly correlated with the normalized passive resistance for each
      velocity whereas no correlation was observed with the raw passive resistance. For
      the patients, except at the highest velocity, the normalized passive resistance
      was not affected by the fact that reflex responses in the triceps surae were
      elicited or not. INTERPRETATION: The normalized passive resistance, expressed
      with respect to the initial one, i.e., measured at very low velocity, seems a
      very effective parameter to quantify the velocity-dependent increase in
      resistance to passive stretch in spastic plantarflexors. However, while the
      simplicity of the isokinetic tests and the reduced time of data treatment seems
      to support the clinical use of this methodology, further investigations are
      required to definitely standardize the protocol.

PMID- 15964115
TI  - Estimation of sources and inflow of dioxins and polycyclic aromatic hydrocarbons
      from the sediment core of Lake Suwa, Japan.
AB  - To elucidate the historical changes in polychlorinated dibenzo-p-dioxin (PCDD),
      polychlorinated dibenzofuran (PCDF), coplanar polychlorinated biphenyl (co-PCB),
      and polycyclic aromatic hydrocarbon (PAH) inflows in Lake Suwa, their
      concentrations in the sediment core were analyzed in 5 cm interval. The maximum
      concentrations (depth cm) of PCDDs/DFs, co-PCBs, and PAHs were 25.2 ng/g dry (30
      35 cm), 19.0 ng/g dry (30-35 cm), and 738, 795 ng/g dry (50-55 cm, 30-35 cm),
      respectively. Age and sedimentation rate of the sediment were estimated from the
      vertical changes in apparent density. Deposition rate of dioxins and PAHs were
      calculated from the concentration and sedimentation rate of the sediment. The
      results indicate that large amounts of dioxins and PAHs flowed into the lake in
      flood stage compared to normal stage.

PMID- 15964116
TI  - Fine roots in stands of Fagus sylvatica and Picea abies along a gradient of soil
      acidification.
AB  - Root length of naturally grown young beech trees (Fagus sylvatica L.) was
      investigated in 26 forest plots of differing base saturation and nitrogen
      deposition. The relative length of finest roots (<0.25 mm) was found to decrease
      in soils with low base saturation. A similar reduction of finest roots in plots
      with high nitrogen deposition was masked by the effect of base saturation. The
      formation of adventitious roots was enhanced in acidic soils. The analysis of 128
      soil profiles for fine roots of all species present in stands of either Fagus
      sylvatica L., Picea abies [Karst.] L. or both showed a decreased rooting depth in
      soils with < or =20% base saturation and in hydromorphic soils. For base rich,
      well drained soils an average rooting depth of 108 cm was found. This decreased
      by 28 cm on acidic, well drained soils. The results suggest an effect of the
      current soil acidification in Switzerland and possibly also of nitrogen
      deposition on the fine root systems of forest trees.

PMID- 15964117
TI  - Simulation of consumer exposure to deoxynivalenol according to wheat crop
      management and grain segregation: case studies and methodological considerations.
AB  - We combined agronomic data and a model simulating exposure based on consumption
      data to assess the impact of crop management and grain segregation procedures on
      consumer exposure to deoxynivalenol. We used three scenarios of soil tillage at a
      regional scale and three scenarios of grain segregation for a supply area. The
      soil tillage scenarios were applied to a range of mean crop contamination levels,
      with various coefficients representing the degree of tillage. The grain
      segregation scenarios were applied to two real datasets of DON content
      distributions. We found that the increase in consumer exposure in response to
      increases in "risky" crop management practices such as direct-drilling depends
      largely on mean contamination and on the value of the tillage coefficient. The
      results for grain segregation procedures showed that exposure was most strongly
      affected by contamination distributions as the segregation procedure minimising
      risk differed for the two datasets.

PMID- 15964118
TI  - Effects of anthocyanidin on the inhibition of proliferation and induction of
      apoptosis in human gastric adenocarcinoma cells.
AB  - Anthocyanins are naturally occurring reddish pigments that abundant in fruits and
      vegetables. To investigate the mechanistic basis for the anti-tumor properties of
      anthocyanins, five aglycone (cyanidin, delphinidin, malvidin, pelargonidin, and
      peonidin) and four glycosylated (cyanidin-3-glucoside, malvidin-3-glucoside,
      pelargonidin-3-glucoside and peonidin-3-glucoside) anthocyanins were used to
      examine their effects on cell cycle progression and induction of apoptosis in
      human gastric adenocarcinoma AGS cells. The data from cell viability assay showed
      that malvidin exhibited the most potent anti-proliferation effect on AGS cells in
      a time- and dose-dependent manner (P<0.05). This event is accompanied the arrest
      of AGS cells at the G0/G1 phase by malvidin at the tested concentrations of 0-200
      microM. Cellular uptake of anthocyanin and anthocyanidin was confirmed by HPLC
      analysis and the intracellular accumulation of malvidin (24.9+/-1.1 microM/mg
      protein) was observed when treatment of AGS cells with malvidin for 12 h. In
      addition, an accumulation of AGS cells in sub-G1 phase (20% and 30% increase for
      100 and 200 microM of malvidin, respectively) was observed as well as by the
      appearance of a fraction of cells with an aneudiploid DNA content. The occurrence
      of apoptosis induced by malvidin was confirmed by morphological and biochemical
      features, including apoptotic bodies formation, caspase-3 activation and poly(ADP
      ribose) polymerase proteolysis. Furthermore, the mitochondrial membrane potential
      of apoptotic cells after treatment with malvidin was significantly lost and
      resulted in the elevation of Bax/Bcl-2 ratio for 1.6-fold against control for 100
      microM treatment. In addition, the malvidin treatment significantly increased the
      p38 kinase expression and inhibited the ERK activity, and the effects of malvidin
      on caspase-3 activation were blocked, respectively, by the ERK and p38
      inhibitors. These findings suggest that growth inhibition and cytotoxicity of AGS
      cells by malvidin is involved in the induction of apoptosis rather than necrosis.

PMID- 15964119
TI  - Effect of zinc supplementation on ethanol-mediated bone alterations.
AB  - Ethanol consumption leads to bone alterations, mainly osteoporosis. Ethanol
      itself may directly alter bone synthesis, but other factors, such as accompanying
      protein malnutrition--frequently observed in alcoholics, chronic alcoholic
      myopathy with muscle atrophy, alcohol induced hypogonadism or hypercortisolism,
      or liver damage, may all contribute to altered bone metabolism. Some data suggest
      that zinc may exert beneficial effects on bone growth. Based on these facts, we
      analyzed the relative and combined effects of ethanol, protein malnutrition and
      treatment with zinc, 227 mg/l in the form of zinc sulphate, on bone histology,
      biochemical markers of bone formation (osteocalcin) and resorption (urinary
      hydroxyproline excretion), and hormones involved in bone homeostasis (insulin
      growth factor 1 (IGF-1), vitamin D, parathormone (PTH), free testosterone and
      corticosterone), as well as the association between these parameters and muscle
      fiber area and liver fibrosis, in eight groups of adult Sprague Dawley rats fed
      following the Lieber de Carli model during 5 weeks. Ethanol showed an independent
      effect on TBV (F=14.5, p<0.001), causing it to decrease, whereas a low protein
      diet caused a reduction in osteoid area (F=8.9, p<0.001). Treatment with zinc
      increased osteoid area (F=11.2, p<0.001) and serum vitamin D levels (F=3.74,
      p=0.057). Both ethanol (F=45, p<0.001) and low protein diet (F=46.8, p<0.01)
      decreased serum osteocalcin levels. Ethanol was the only factor independently
      related with serum IGF-1 (F=130.24, p<0.001), and also showed a synergistic
      interaction with protein deficiency (p=0.027). In contrast, no change was
      observed in hydroxyproline excretion and serum PTH levels. No correlation was
      found between TBM and muscle atrophy, liver fibrosis, corticosterone, or free
      testosterone levels, but a significant relationship was observed between type II
      b muscle fiber area and osteoid area (rho=0.34, p<0.01). Osteoporosis is,
      therefore, present in alcohol treated rats. Both alcohol and protein deficiency
      lead to reduced bone formation. Muscle atrophy is related to osteoid area,
      suggesting a role for chronic alcoholic myopathy in decreased bone mass.
      Treatment with zinc increases osteoid area, but has no effect on TBV.

PMID- 15964121
TI  - Apoptosis of blood mononuclear cells in alcoholic liver cirrhosis. The influence
      of in vitro ethanol treatment and zinc supplementation.
AB  - Ethanol consumption induces apoptosis in a variety of tissues, among others in
      liver and lymphoid tissue. Zinc has been shown to influence apoptosis of blood
      mononuclear cells by inhibiting the mitochondrial pathway of cell death. The aim
      of this study was to examine the influence of zinc on spontaneous and in vitro
      alcohol-induced apoptosis of peripheral blood mononuclear cells (PBMCs) of
      patients with alcoholic cirrhosis. PBMCs were isolated from the blood of 26
      patients with cirrhosis and 20 healthy controls. PBMCs and among them CD4+ T
      helper cells of cirrhotic patients exhibited accelerated spontaneous (without
      treatment) apoptosis in vitro. When apoptosis was induced in vitro by treating
      cells with 80 mM ethanol, CD8+ T lymphocytes of a healthy control were more
      sensitive to ethanol treatment than those of cirrhotic patients. Thirty
      micromolar zinc supplementation inhibited both spontaneous and ethanol-induced
      apoptosis of immune cells derived from the blood of the healthy control and
      cirrhotic patients. In sera of patients with cirrhosis, an elevated level of IL
      12, but also sFas (CD95) and sFas ligand (sFasL) was detected. Moreover, in
      vitro, PBMCs of cirrhotic patients spontaneously released more sFas and sFasL
      than control PBMCs. Ethanol treatment significantly increased sFas, but decreased
      sFasL release from PBMCs of cirrhotic patients, while it only slightly affected
      control cells. As zinc supplementation did not significantly influence sFas or
      sFasL release, it seems likely that it is rather the mitochondrial pathway of
      ethanol-related immune cell death that may be inhibited by zinc supplementation.

PMID- 15964122
TI  - Quality of prehospital CPR based on AED records.

PMID- 15964123
TI  - Providing automated external defibrillators to urban police officers in addition
      to a fire department rapid defibrillation program is not effective.
AB  - OBJECTIVE: The aim of this study was to determine if providing automated external
      defibrillators (AEDs) to urban police officers would increase the proportion of
      patients with out-of-hospital cardiac arrest (OOH-CA) who were discharged alive
      from the hospital. METHODS: This prospective, controlled study was conducted in a
      city with about 332,000 persons. The EMS system included paramedic ambulances and
      fire department based first responders equipped with defibrillators, but police
      officers did not respond routinely to medical emergencies. Between March 1997 and
      February 1999, all OOH-CAs in four police districts were identified and followed
      until death or hospital discharge. All 35 police cars in one police district were
      provided with AEDs, and all police officers in that district were trained in CPR
      and the use of AEDs. Police and fire first response units were dispatched
      simultaneously in district 3 (intervention group). Fire first response was
      dispatched without police in districts 2, 4, and 5 (control group). RESULTS: A
      total of 645 OOH-CAs occurred over the 2 years. Sixty-two were outside of the
      study area. Two did not have accurate address information to determine the police
      district. Of the remaining cases, 154 (27%) occurred in the intervention district
      and 427 (73%) were in the control area. Survival to hospital discharge was
      similar; it was 11/154 (7.1%) in the intervention and 16/427 (3.8%) in the
      control districts (odds ratio=1.98; 95% CI 0.90--4.36). Survival to hospital
      discharge for witnessed OOH-CA events occurring prior to EMS arrival and found to
      be in ventricular fibrillation or ventricular tachycardia was 4/27 (15%) in the
      intervention area and 9/73 (12%) in the control area (odds ratio=1.2; 95% CI 0.4
      4.4). CONCLUSION: Equipping police cars with AEDs in an urban area where the fire
      department-based first response system also carries defibrillators did not
      improve the hospital discharge survival rate for victims of OOH-CA.

PMID- 15964124
TI  - Multi-centre study of intraurethral valve-pump catheter in women with a
      hypocontractile or acontractile bladder.
AB  - OBJECTIVES: To compare the safety, effectiveness and patient satisfaction of an
      intraurethral valve-pump catheter (In-Flow) versus the current standard of care,
      clean intermittent catheterization (CIC), for females with hypocontractile or
      acontractile bladder. MATERIALS AND METHODS: The study was a multi-centre,
      prospective, single-arm crossover study. Eligible patients underwent a 1-week In
      Flow tolerability trial. Successful patients then continued through an 8-week
      baseline phase using CIC, followed by a 16-week In-Flow treatment phase, and a
      final 4-week treatment withdrawal phase. Outcome measures included post-void
      residual (PVR), Wagner incontinence-specific quality of life (I-QOL), rate of
      urinary tract infection and adverse events. At study completion, open enrollment
      was offered. RESULTS: A total of 273 women with a mean age of 48.9 years using
      CIC entered the study in 18 centres under either the original (n=88) or revised
      protocols (n=185). The revised protocol included the addition of a 1-week
      tolerability trial. The reasons for the large early withdrawal of subjects
      (169/273) were mainly related to initial discomfort and leakage. A total of 77
      patients completed the In-Flow treatment phase. PVR was comparable during
      baseline CIC phase and In-Flow treatment phase (20.3 ml vs. 16.1 ml), with
      significantly improved quality of life (QOL; mean improvement of I-QOL score
      +25.9; p<0.001). CONCLUSION: The In-Flow catheter appears to be a viable
      alternative to CIC. A subgroup of patients, mainly those unsatisfied with the
      currently available treatments, was more likely to tolerate In-Flow catheters,
      and they may achieve enhanced independence and QOL.

PMID- 15964125
TI  - Proteome analysis of gelatin-bound urinary proteins from patients with bladder
      cancers.
AB  - OBJECTIVES: Proteome analysis with protein separation by two-dimensional
      polyacrylamide gel electrophoresis (2-D PAGE) and mass spectrometric measurement
      is utilized for comprehensive identification of proteins in various biological
      samples. However, this technique has not been widely applied for the analysis of
      body fluid for clinical assessments, because large amounts of proteins in fluid
      such as albumin and globulin hinder the detection of small amounts of proteins
      with high clinical values. The aim of the present study is to develop a method of
      proteomic analysis for urine of patients with bladder cancers. MATERIALS AND
      METHODS: Urine samples collected from 40 patients with bladder cancers, 32
      healthy volunteers, and 7 old volunteers with benign prostate hypertrophy were
      treated with gelatin-beads as a group-specific affinity carrier. The gelatin
      bound proteins were subjected to the proteome analysis. RESULTS: Various amounts
      of matrix metalloproteinase-2 (MMP-2), -9 (MMP-9), fibronectin (FN), and their
      fragments were identified on 2-D PAGE gels from cancer-bearing patients, but not
      from normal individuals. Importantly, not only total amounts of these proteins,
      but also patterns of their distributions on the gels were well matched with the
      extent of invasion diagnosed with histopathological examinations. Thus, the score
      including such qualitative patterning of these proteins predicts pathological
      stages of the cancer. CONCLUSION: The proteomic analysis with gelatin-affinity
      purification of urine samples is useful not only for the diagnosis of bladder
      cancers, but also for estimating the extent of tumor invasion.

PMID- 15964126
TI  - Nerve replacement strategies for cavernous nerves.
AB  - OBJECTIVE: This article reviews novel restorative therapies for cavernous nerves
      that may be used to replace resected cavernous nerves at the time of pelvic
      surgery. METHODS: A literature-based presentation (Medline search) on current
      nerve replacement strategies was conducted with emphasis on neurobiological
      factors contributing to the restoration of erectile function after cavernous
      nerve injuries. RESULTS: A promising alternative to autologous nerve grafts for
      extending the length of successful nerve regeneration are artificial nerve
      guides. The addition of neurotrophic factors, extracellular matrix components and
      Schwann cells has been shown to promote cavernous nerve regeneration.
      Neurotrophic factors can be incorporated in the scaffold or can be supplied by
      cells seeded into the stroma. The regenerative capacity of these cells can be
      further enhanced by genetic modification with neurotrophic factor encoding genes.
      CONCLUSIONS: Artificial nerve guides, especially biodegradable ones containing
      growth-promoting factors or cells, are a promising option for the repair of
      cavernous nerve lesions.

PMID- 15964127
TI  - Histological subtyping and nuclear grading of renal cell carcinoma and their
      implications for survival: a retrospective nation-wide study of 629 patients.
AB  - OBJECTS: The aim of this study was to evaluate the prognostic significance of the
      current WHO histological subtyping and Fuhrman nuclear grading on the survival of
      patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: A retrospective
      population-based study was carried out on all patients with a histopathologically
      confirmed diagnosis of RCC in Iceland between 1971 and 2000. Fuhrman grade, TNM
      stage, and survival were evaluated and multivariate analysis applied in order to
      determine prognostic factors. RESULTS: Out of 629 patients (387 males, 242
      females, mean age 64 years), 558 (88.7%) had clear cell, 53 (8.4%) papillary, and
      13 (2.1%) chromophobe RCC. Patient demographics were comparable for the two major
      subtypes, but chromophobe RCCs were larger in size and were diagnosed at a
      younger age. Clear cell RCCs were more often of higher grades (G3+G4, 48.4%) and
      at advanced TNM stages (III+IV, 59.3%) than papillary RCCs (22.6% and 34%
      respectively, p<0.001). Linear regression analysis showed a strong correlation
      between grade, tumor size, and stage (p<0.001). Chromophobe RCCs had a better
      survival in univariate analysis than both papillary and clear cell RCCs (84.6%
      vs. 66.5% and 54.9% 5-year disease specific survival, p<0.001). However, in the
      multivariate analysis, only the patient's age, calendar year of diagnosis, TNM
      stage, and nuclear grade were independent prognostic factors of survival.
      CONCLUSION: In this complete nation-wide series nuclear grading is important in
      predicting survival of patients with RCC. It is strongly related to both tumor
      size and stage, with stage being by far the strongest prognostic factor.
      Different histological subtypes confer different survival. However, in spite of
      the distinctive cytogenetic and molecular characteristics of the subtypes, the
      survival difference is to a large extent due to differences in grade and
      particularly stage.

PMID- 15964128
TI  - Lower urinary tract symptoms in patients with erectile dysfunction: is there a
      vascular association?
AB  - OBJECTIVE: To assess if there is an underlying vascular association between lower
      urinary tract symptoms (LUTS) and erectile dysfunction (ED). MATERIALS AND
      METHODS: A total of 374 male patients with ED were enrolled in this study.
      Patients were interviewed for ED using the International Index of Erectile
      Function. Assessments for penile vasculature using color Doppler ultrasonography
      and rigidometer were performed. All patients were also screened for LUTS using
      the International Prostate Symptoms Score. All patients underwent routine
      laboratory investigation, plus total testosterone and prolactin assessment.
      RESULTS: Mean age+/-SD was 54.4+/-8.9 years with an age range of 28-84 years.
      Eighty-five percent of the patients had organic causes of ED. Of the patients,
      80.7% had different degrees of LUTS. There was a significant association between
      presence of LUTS and: arteriogenic and neurogenic causes of ED, poor response to
      intracorporeal injection, poor rigidity in the rigidometer, and low peak systolic
      velocity of the cavernosal arteries (p < 0.05 for each). No significant
      association was found between presence of LUTS and increasing values of end
      diastolic velocity or decreasing values of resistive index of the cavernosal
      arteries (p > 0.05 for each). There was a significant association between the
      higher degrees of LUTS and the decreasing values of peak systolic velocity (p <
      0.05). CONCLUSIONS: This study demonstrated that reduced peak systolic velocity
      of the cavernous artery does associate with LUTS in patients with erectile
      dysfunction. Further studies are warranted to address the underlying vascular
      mechanisms of ED in patients with LUTS.

PMID- 15964129
TI  - Training on bench models improves dexterity in ureteroscopy.
AB  - INTRODUCTION: There is a need for alternative training in endourology.
      Computerised simulators have been introduced but have, so far, not been compared
      to real surgery. Bench models have proved to be comparable to real surgery when
      performing standard procedures in the upper urinary tract. OBJECTIVE: To validate
      training on bench models as a tool to improve dexterity in semi-rigid
      ureteroscopy. METHODS: Urology residents were tested when performing semi-rigid
      ureteroscopy on a bench model (Mediskills), before and after training. All
      standard equipment and instruments, including fluoroscopy, were available. For
      the test procedure we used a task-specific checklist and a global score (maximum
      score 10 + 9 = 19). After base line assessment, the participants practised under
      supervision. After training they were reassessed, using the same procedure as
      previously. RESULTS: The performance was significantly better after the training.
      Results before/after were: 5.1/9.2, 2.6/7.8 and 7.7/17.2 for task-specific
      checklist, global score and total score respectively. All residents felt more
      familiar with the instruments and the procedure after the training. CONCLUSION:
      Training on bench models for ureteroscopy enhanced the manual dexterity as well
      as familiarity with the method and is recommendable before operating on patients.

PMID- 15964130
TI  - The treatment satisfaction scale: a multidimensional instrument for the
      assessment of treatment satisfaction for erectile dysfunction patients and their
      partners.
AB  - BACKGROUND: The development of the Treatment Satisfaction Scale (TSS) was
      previously reported (Kubin et al., 2004). OBJECTIVE: This article describes the
      psychometric validation process and psychometric properties (e.g., reliability,
      validity, and responsiveness) of TSS. METHODS: Initial patient and partner
      questionnaires were administered in a multi-national clinical trial. On the basis
      of exploratory analyses, iterative psychometric testing, and consideration of
      face validity and interpretability, the number of items was reduced, and six
      scales were constructed: "Satisfaction with Medication," "Ease with Erection,"
      "Satisfaction with Erectile Function," "Pleasure from Sexual Activity,"
      "Satisfaction with Orgasm," and either "Sexual Confidence" (for patients) or
      "Confidence in Completion" (for partners). RESULTS: Multi-item scales had good
      internal consistency reliability and concurrent validity with the IIEF. All
      patient scales and most partner scales were valid in relation to clinical
      criteria, and all tested scales were responsive to change over time. CONCLUSION:
      The TSS is brief, culturally valid, and the most comprehensive multidimensional
      measure of satisfaction with ED treatment for patients and their partners, and
      addresses some of the shortcomings of existing measures.

PMID- 15964131
TI  - Uterus preservation in surgical correction of urogenital prolapse.
AB  - OBJECTIVE: This study aimed to evaluate the efficacy of colposacropexy with
      uterine preservation as therapy for uterovaginal prolapse. Surgical techniques,
      efficacy and overall results are described. METHODS: In this prospective,
      controlled study, 34 of the 72 consecutive patients with symptomatic uterovaginal
      prolapse were treated with colposacropexy with uterus conservation
      (hysterocolposacropexy, HSP) and the other 38 with hysterectomy followed by
      sacropexy (CSP). Anchorage was achieved with two rectangular meshes in CSP and
      with one posterior rectangular and one anterior Y-shaped mesh in HSP. Check-ups
      were scheduled at 3, 6 and 12 months and then yearly. Pre-operative patient
      characteristics, operative and post-operative events and follow-up results were
      recorded. Mean follow-up was 51 months (range 12-115). RESULTS: No significant
      differences emerged in demographic and clinical characteristics between the HSP
      and CSP groups. Mean operating times, intra-operative blood loss and hospital
      stay were significantly less after HSP (p<0.001). At follow-up success rates were
      similar in the two groups in terms of uterine and upper vaginal support (100%).
      Recurrent low-grade cystoceles developed in 1/38 (2.6%) in the CSP group and in
      5/34 (14.7%) in the HSP group (p=NS), recurrent low-grade rectocele developed in
      6/38 (15.8%) and in 3/34 (8.8%) patients respectively (p=NS). No patient required
      surgery for recurrent vault or uterus prolapse. Urodynamic results showed that
      pressure/flow parameters improved significantly (p<0.001) in both groups. Thirty
      one of the 34 patients (91%) in the HSP group and 33/38 (86.8%) in the CSP group
      were satisfied and would repeat surgery again. CONCLUSIONS: Colposacropexy
      provides a secure anchorage, restoring an anatomical vaginal axis and a good
      vaginal length. HSP can be safely offered to women who request uterine
      preservation. Whether the uterus was preserved or not, patients had similar
      results in terms of prolapse resolution, urodynamic outcomes, improvements in
      voiding and sexual dysfunctions. HSP has shorter operating times and less blood
      loss.

PMID- 15964132
TI  - Do prostatic infarction, prostatic inflammation and prostate morphology play a
      role in acute urinary retention?
AB  - OBJECTIVE: To investigate whether there is a role of prostatic infarction,
      prostatic inflammation and prostate morphology in acute urinary retention (AUR)
      etiology. METHODS: Ninety-eight consecutive male patients who were admitted to
      our clinic with either AUR or lower urinary tract symptoms (LUTS) were involved
      in the study. Patient age ranged from 43 to 88 years (median age 70). Group 1
      consisted of 53 (54%) patients with AUR, and Group 2 consisted of 45 (46%)
      patients with LUTS. In Group 1 and Group 2, 58.4% (n:31) and 62.2% (n:28) of the
      patients underwent transurethral prostate resection, 41.6% (n:22) and 37.8%
      (n:17) of the patients underwent suprapubic transvesical prostatectomy,
      respectively. Each patient was asked about the factors: smoking habits, taking
      previous general anesthesia and preexisting cardiovascular disease such as
      hypertention and atherosclerotic coronary vascular disease which may lead to AUR
      via prostatic infarct. Prostatic infarction, prostatic inflammation and prostatic
      morphology were examined in the patients' specimen. RESULTS: Mean age, median
      serum prostate-specific antigen (PSA) level, and prostatic inflammation ratio
      were significantly higher in Group 1. There were not significant differences
      between the groups regarding prostate volume, prostatic infarction ratio and a
      type of prostatic morphology. In the present study, except for taking previous
      general anesthesia and preexisting cardiovascular disease, only prostatic
      inflammation was found important contributory factor on AUR. AUR risk was 3.03
      times higher in the patients with prostatic inflammation (95%CI 1.28-7.15) (p =
      0.01). CONCLUSIONS: No significant effect of prostatic infarction was found on
      occurrence of AUR which was more frequent in elderly patients. Prostatic
      inflammation may have an important risk factor in AUR etiology. Additionally,
      serum PSA levels were higher in AUR group. No association was found between a
      type of prostatic morphology and AUR.

PMID- 15964133
TI  - Prevalence of the overactive bladder syndrome by applying the International
      Continence Society definition.
AB  - PURPOSE: To determine the prevalence of the overactive bladder (OAB) syndrome in
      an urban population by using the International Continence Society (ICS)
      definition and to determine its impact on quality of life and sexual function.
      METHODS: Women and men participating in a health screening project in the area of
      Vienna completed the Bristol Lower Urinary Tract Symptoms (LUTS) questionnaire.
      To assess the prevalence of OAB the 2002 ICS definition was applied. In addition,
      all participants underwent a detailed health examination, including physical
      assessment, evaluation of life style factors, laboratory study and urinalysis.
      RESULTS: A total of 1199 men and 1219 women aged 20-91 years were analysed. The
      prevalence of OAB in men (48.5+/-13.1 years) was 10.2% (OABdry: 8.4%; OABwet:
      1.8%) and 16.8% in women (49.5+/-13.5 years; OABdry:10.3%; OABwet: 6.5%). In
      women, the prevalence of OABdry remained fairly stable over 6 life decades, while
      OABwet increased substantially after the age of 40 years. In men OABwet and
      OABdry increased after the third life decade. In men with OAB, 48% did not report
      a negative impact on quality of life, 36% had minimal, 9.8% moderate and 2.5%
      severe impairment; the respective percentages for women were 53%, 33%, 7.3% and
      6.3%. OABwet had a more profound impact on quality of life. A negative impact of
      OAB on sexuality was reported by 24% of men and 31% of women. CONCLUSION: The
      high prevalence of OAB in this population, its negative impact of quality of life
      and sexuality underline the importance of this syndrome.

PMID- 15964134
TI  - The efficacy of different follow-up strategies in clinical stage I Non
      seminomatous Germ Cell Cancer: a Markov simulation study.
AB  - OBJECTIVE: There is no universally accepted standard protocol for surveillance of
      patients with clinical stage I Non Seminomatous Germ Cell Tumors (CS I NSGCT).
      Prospective studies to compare different follow-up policies have not been
      performed, even though a great deal of time and resources is spent in
      surveillance. In this study, we constructed a Markov model to evaluate the impact
      of different follow-up strategies on disease-specific mortality (DSM) and life
      expectancy (LE) of patients with CS I NSGCT. METHODS: A discrete time non
      homogeneous semi-Markov model was used to simulate different follow-up strategies
      for a hypothetical population of CS I NSGCT patients. Estimates of the model
      parameters were based on the literature. Output parameters were DSM and LE. Three
      different strategies were compared: (1) the intensive The Netherlands Cancer
      Institute/Antoni van Leeuwenhoek hospital (NCI/AvL) protocol; (2) the European
      Association of Urology (EAU) protocol; and (3) a hypothetical minimal protocol
      (i.e. follow-up limited to the first two years). Furthermore, we evaluated the
      impact of abdominal CT scans and chest X-rays on DSM. RESULTS: Comparing with the
      EAU protocol (DSM: 3.05%; LE: 53.3 years), the intensive NCI/AvL protocol leads
      to a 1.2% lower DSM and a 6 months higher LE (DSM: 1.81%; LE: 53.9 years). The
      hypothetical follow-up scenario during the first two years shows a DSM of 6.83%
      and an LE of 51.4 years. Abdominal CT scans of the retroperitoneal lymph nodes
      appear to be important, while chest X-rays have little impact on DSM. CONCLUSION:
      A follow-up policy limited to the first two years will result in an unacceptable
      high percentage of death from disease (6.83%). The relatively small benefit of an
      intensive follow-up protocol as proposed by the NCI/AvL, compared to that of the
      EAU, must be weighed against its economic and psychological costs. Our model
      suggests that CT-scanning is essential for a low DSM, whereas the large number of
      X-rays seem to have little additional effect.

PMID- 15964135
TI  - The first human trial for gene transfer therapy for the treatment of erectile
      dysfunction: preliminary results.
AB  - OBJECTIVE: To test the safety of a single intracavernous injection of a plasmid
      vector (hMaxi-K) that expresses the hSlo gene, that encodes the alpha-subunit of
      the Maxi-K channel, for the treatment of erectile dysfunction (ED). METHODS: Six
      men, thus far have fulfilled the entry criteria of the protocol and had gene
      transfer with hMaxi-K. Three received a dose of 500 microg and three received a
      dose 1000 microg of the gene product, injected intracavernously as naked DNA.
      Dosing at 5000 microg and higher is planned. RESULTS: The primary end point of
      the phase I trial is safety. No drug-related adverse events or significant
      laboratory changes have occurred after the gene transfer. Moreover, there is no
      evidence of the gene in semen at the one copy per mug total DNA in any of the
      participants. CONCLUSION: Preliminary results indicate that, in a single dose
      escalation study, ion channel gene transfer with hMaxi-K can be administered
      safely to men with ED without adverse events.

PMID- 15964136
TI  - Recent advances in conventional-dose salvage chemotherapy in patients with
      cisplatin-resistant or refractory testicular germ cell tumors.
AB  - Testicular germ cell tumors represent the most frequent malignancy in young males
      aged 20-35 years. Despite the considerably high cure rates provided by platinum
      based chemotherapy, 20-30% of cases with advanced disease do not achieve a long
      term disease-free survival with first-line chemotherapy. These patients are
      candidates for conventional-dose or high-dose salvage chemotherapy. The current
      conventional-dose salvage regimens of reference are the vinblastine-ifosfamide
      cisplatin or etoposide-ifosfamide-cisplatin combinations, which are expected to
      cure approximately 25% of non-seminomatous germ-cell tumour patients. Paclitaxel
      has also been proved effective both as monotherapy in heavily-pretreated cases
      and as part of first-line salvage regimens; the combination of paclitaxel
      ifosfamide-cisplatin, followed or not by high-dose chemotherapy, induced a
      favorable long-term disease-free survival rate, especially in patients with good
      prognosis. Newer cytotoxic drugs, such as gemcitabine and oxaliplatin have also
      been proved effective, while other agents, such as temozolamide, or targeted
      therapies, such as trastuzumab in cases over-expressing HER2/neu (20% of
      relapsing germ-cell tumors) are currently under evaluation. Seminomas have
      generally a better prognosis than non-seminomatous tumors and salvage therapy is
      expected to cure about 50% of all cases.

PMID- 15964138
TI  - Successful application of targeted electrochemotherapy using novel flexible
      electrodes and low dose bleomycin to solid tumours.
AB  - Electroporation is the application of very brief electric pulses to cells or
      tissues to render the cell membranes transiently and reversibly permeable,
      facilitating cellular uptake of otherwise impermeant molecules. Flexible
      electrode arrays were developed which may be used with endoscopic and
      laparoscopic devices for delivery of therapeutic electroporation. Their efficacy
      in enhancing the delivery of bleomycin, an impermeant drug, was assessed in vitro
      and in vivo in both human and murine cancer cell lines, and growing tumours
      (xenografts). These flexible electrodes consistently and predictably deliver the
      permeabilising electric pulses requisite for in vivo electroporation, and would
      be suitable for electrochemotherapy of endoluminal tumours when incorporated into
      an endoscopic delivery system.

PMID- 15964137
TI  - Anthrax lethal toxin represses glucocorticoid receptor (GR) transactivation by
      inhibiting GR-DNA binding in vivo.
AB  - Anthrax lethal factor (LF) is a non-competitive repressor of glucocorticoid (GR)
      and progesterone receptor (PR) transactivation. This repression was shown to be
      specific and selective and was dependent on promoter context and receptor
      subtype. Anthrax lethal toxin (LeTx) selectively repressed GR-mediated
      transactivation but not transrepression. The DNA binding region of GR was
      required for repression by LeTx and LeTx prevented GR-DNA binding in vivo, which
      had downstream consequences on polymerase II binding and histone acetylation. In
      addition, LeTx also prevented the accessory protein C/EBP from binding to a GR
      responsive promoter. We hypothesize that LeTx may remove/inactivate one of the
      many co-factors or accessory proteins that are required to stabilize the GR-DNA
      complex. These findings enhance the current knowledge of the molecular mechanism
      by which the anthrax lethal factor represses nuclear hormone receptors and could
      provide an approach to overcome some of LeTx's effects.

PMID- 15964139
TI  - Recovery of H2SO4 from waste acid solution by a diffusion dialysis method.
AB  - A diffusion dialysis method using anion exchange membrane was used to recover
      H2SO4 from waste sulfuric acid solution produced at the diamond manufacturing
      process. Effects of flow rate, operation temperature, and metal ion concentration
      on the recovery of H2SO4 were investigated. The recovery of H2SO4 increased with
      the concentration of H2SO4 and operation temperature. It also increased with the
      flow rate ratio of water/H2SO4 solution up to 1, above which no further increase
      was observed. The flow rate did not affect the rejection of Fe and Ni ions. About
      80% of H2SO4 could be recovered from waste sulfuric acid which contained 4.5M
      free-H2SO4 at the flow rate of 0.26x10(-3) m3/hm3. The concentration of recovered
      H2SO4 was 4.3M and the total impurity was 2000 ppm. Preliminary economic
      evaluation has revealed that the dialysis system is highly attractive one that
      has payback period of only few months.

PMID- 15964140
TI  - Gene expression profiling of the rat hippocampus one month after focal cerebral
      ischemia followed by enriched environment.
AB  - Functional recovery after experimental stroke in rats is enhanced by
      environmental enrichment by stimulating plastic changes in brain regions outside
      the lesion, but the molecular mechanisms are not known. We investigated the
      effect of environmental enrichment after focal cerebral ischemia on cognitive
      recovery and hippocampal gene expression using microarray analysis. Rats placed
      in enriched environment (EE) for 1 month after middle cerebral artery occlusion
      (MCAo) showed significantly improved spatial memory in the Morris water maze
      compared to rats housed alone after MCAo. Microarray analysis suggested several
      EE-induced differences in neuronal plasticity-related genes, but these changes
      could not be confirmed by quantitative real-time PCR. This study highlights some
      of the potential problems associated with gene expression profiling of brain
      tissues. Further studies at earlier time points and in additional subregions of
      the brain are of interest in the search for molecular mechanisms behind EE
      induced neuronal plasticity after ischemic stroke.

PMID- 15964141
TI  - Experiments with nitric oxide synthase inhibitors in spinal nerve ligated rats
      provide no evidence of a role for nitric oxide in neuropathic mechanical
      allodynia.
AB  - We have investigated the effect of treatment with N(omega)-nitro-l-arginine
      methylester (l-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both
      before and after the induction of mechanical allodynia by tight ligation of the
      left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical
      allodynia was measured by tactile threshold for paw flinching with von Frey
      filaments. Intraperitoneal (i.p.) administration of l-NAME (3-30 mg/kg) 1 week
      after the spinal nerve ligation produced a dose-dependent reduction of the
      behavioral signs of mechanical allodynia, but the effect was not reversed by
      pretreatment with l-arginine (300 mg/kg). N(omega)-Nitro-l-arginine (l-NNA, i.p.,
      30 mg/kg), aminoguanidine (AG, i.p., 30 mg/kg) and a potent neuronal NOS
      inhibitor (LY457963, i.p., 30 mg/kg) did not reduce mechanical sensitivity in the
      SNL rats. Furthermore, using an ex vivo NOS activity assay, l-NAME partially
      inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited
      the spinal NOS activity. Prior administration of l-NAME (i.p., 30 mg/kg) or of MK
      801 (0.5 mg/kg), an NMDA antagonist, 30 min before the spinal nerve ligation
      significantly prevented the development of mechanical allodynia after spinal
      nerve ligation for an extended period of time. High doses of l-arginine (100
      mg/kg or 300 mg/kg, i.p.), however, did not reverse the preemptive effect of l
      NAME. These results suggest that neither the anti-allodynic nor the preemptive
      effects of l-NAME are mediated by NOS inhibition.

PMID- 15964142
TI  - Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into
      rat sciatic nerve at physiological doses induces signs of neuropathic pain.
AB  - Proinflammatory cytokines are mediators of inflammatory and neuropathic pain.
      Here, we investigated pain-related behavior in rats after intraneural injection
      of different doses of rat recombinant interleukin-1beta (rrIL-1beta) and tumor
      necrosis factor-alpha (rrTNF) into the sciatic nerve. Doses ranged between 0.25
      and 2500pg/ml for rrIL-1beta and 0.25-250pg/ml for rrTNF. Thermal hyperalgesia as
      measured according to the Hargreaves method was most prominent with 2.5pg/ml of
      rrIL-1beta or rrTNF. Mechanical allodynia as assessed using von Frey hairs was
      seen consistently with 2.5pg/ml of rrIL-1beta and 0.25-2.5pg/ml of rrTNF. Higher
      and lower doses had no significant effect on pain-related behavior. Morphometric
      analysis of semithin sections of the sciatic nerve 10 days after the injections
      revealed no significant fiber loss. The fiber size distribution was not
      significantly altered by any of the treatments. Particularly with injections of
      rrIL-1beta, an increase of epineurial macrophages was observed at all doses. The
      immunohistochemical expression of cellular markers of neuronal damage (activating
      transcription factor 3) or activation (phosphorylated p38 mitogen-activated
      kinase, NF-kappa B p65) in dorsal root ganglia (DRG) tended to increase with both
      cytokine injections. However, this did not reflect the extent of behavioral
      changes. In summary, we found a bell-shaped dose-response curve for the algesic
      effects of rrIL-1beta and rrTNF, peaking at doses equivalent to those of
      endogenous cytokines released locally after nerve injury. The absence of
      corresponding morphological changes in nerves supports the concept of a
      functional effect of the cytokines at these doses.

PMID- 15964143
TI  - Cognitive activation theory of stress (CATS): from fish brains to the Olympics.
AB  - The Cognitive Activation Theory of Stress (CATS) offers formal and systematic
      definitions of the terms and concepts used in stress research. The stress
      response depends on acquired expectancies to the outcome of the stimulus and the
      available responses. The stress response itself is an alarm, an increase in
      arousal necessary for performance and adequate reactions to challenges. The
      response is healthy and necessary for survival. Only when sustained over time may
      potential health risks occur. The basic rules for when stress occurs are the same
      across cultures and species, from fish to Olympic performance in humans. The
      important dimensions for health are positive expectancies of outcome (coping),
      control, and safety, for all individuals in all species.

PMID- 15964144
TI  - Chemical sensitivity and the work place environment: research needs.
AB  - Large numbers of studies of multiple chemical sensitivity (MCS) have been
      performed, particularly in clinical settings. Epidemiological studies in the area
      are scarce, and this is also the case for cacosmia. Very few have studied the
      work place conditions for the MCS patient at the onset of symptoms, neither the
      chemical exposure nor psychosocial conditions. This type of research is of
      interest to understand the development of the syndrome and to suggest preventive
      actions in the work places.

PMID- 15964145
TI  - Press stop to start: the role of inhibition for choice and health.
AB  - In order to react adequately to any new challenge, it is necessary to stop all
      ongoing activity. The first phase in the orienting response to a novel stimulus
      is an arrest of all ongoing activity. Inhibition is also necessary to switch from
      one behaviour to another, and from one cognitive activity to another. Inhibition
      was a difficult phenomenon to handle until the role of inhibitory synapses was
      demonstrated, and that many brain areas have an inhibitory function for overt
      behaviour and for establishing new responses in learning experiments. The role of
      these areas for learning and for plasticity of the brain has been well
      established. Recently, the role of inhibition, or lack of inhibition, for
      cognitive activities has been discussed for the understanding of somatization and
      sensitization to afferent somatic impulses. It has been postulated that muscle
      pain is maintained by positive feed back loops between muscles, the spinal cord,
      and the brain areas for pain and interpretation of pain. Activity in these loops
      may lead to sensitisation of the neural circuits, leading to chronic pain states.
      Similar models have been presented for non-specific gastric and intestinal
      complaints, and for fatigue and depression. Rumination and perseveration of
      negative thoughts may maintain the activity in these loops.

PMID- 15964146
TI  - The psychobiology of PTSD: coping with trauma.
AB  - Posttraumatic stress disorder (PTSD) is one of the few psychiatric conditions
      where a specific psychosocial stressor is explicitly tied to etiology. Although a
      majority of people experience a traumatic event in their life, most of them will
      not develop PTSD or other mental health problems such as depressive or anxiety
      disorders. Emotional and neurobiological responses to psychosocial stressors show
      striking individual variation. In this paper cognitive appraisal and coping
      factors are explored as potential sources of individual differences in the
      neuroendocrinological stress response, and subsequently in mental health outcome.
      Continued study of the psychobiology of trauma and PTSD will enhance our
      understanding of adaptation to psychosocial stressors and support efforts to
      treat associated psychological and biological sequelae.

PMID- 15964147
TI  - AVP- and OT-neurophysins response to apomorphine and clonidine in major
      depression.
AB  - A number of studies have reported abnormalities of neurohypophyseal secretions in
      major depressive disorder. The purpose of the present study was to test the
      influence of apomorphine and clonidine injections on plasma vasopressin (AVP)
      neurophysins and oxytocin(OT)-neurophysins levels, as direct index of posterior
      pituitary activation in major depression. Apomorphine and clonidine tests were
      carried out in 25 medication-free depressive patients and 25 age and gender
      matched healthy controls. Blood for neurophysins analysis was drawn by
      venipuncture at t0, t + 20, t + 40, t + 60 and t + 120. Baseline AVP-neurophysins
      concentrations were significantly lower in depressives (0.12 +/- 0.14 ng/ml) than
      in healthy subjects (0.24 +/- 2.15 ng/ml) (p < 0.04). The response to apomorphine
      test revealed a significant reduced response at 20 (p = 0.01), 40 (p = 0.007) and
      60 (p = 0.02) and 120 (p = 0.02)min. Following clonidine test, post hoc tests
      also revealed a significant decrease at 0 (p = 0.04), 20 (p = 0.01), 40 (p =
      0.007) and 60 (p = 0.02) and 120 (p = 0.006)min. Concerning OT-neurophysins, no
      significant differences were found between depressed and controls in response to
      clonidine or apomorphine injections. Following clonidine and apomorphine, major
      depressives exhibited a significantly lower peak GH response than controls. The
      study supports partially the hypothesis of a reduced vasopressinergic activity in
      depression. Moreover, we did not find any influence of acute apomorphine or
      clonidine injections on vasopressin-neurophysin or oxytocin-neurophysin in
      depressive patients.

PMID- 15964148
TI  - Individual differences in childhood neurobehavior disinhibition predict decision
      to desist substance use during adolescence and substance use disorder in young
      adulthood: a prospective study.
AB  - Genetic, physiological and psychological investigations have demonstrated that
      deficient inhibitory regulation amplifies the risk for substance use disorder
      (SUD). This study extends this line of research by determining the association
      between childhood neurobehavior disinhibition and decision to desist substance
      use following prevention intervention during adolescence. The sample consisted of
      302 boys who were evaluated at ages 10-12, 12-14, 16, and 19. Results indicated
      that childhood neurobehavior disinhibition negatively covaried with decision to
      desist substance use during adolescence. These two variables predicted
      acceleration of drug consumption frequency during adolescence and DSM-IV
      diagnosis of SUD by age 19. Decision to desist drug use did not mediate the
      association between neurobehavior disinhibition and substance use/SUD. The
      findings indicate that substance abuse prevention would be potentiated by
      ameliorating childhood neurobehavior disinhibition.

PMID- 15964149
TI  - Gray's model of personality and addiction.
AB  - It has been suggested that high levels of behavioral approach system (BAS)
      sensitivity predispose psychopathological conditions that are characterized by a
      pathological engagement in approach behaviors, such as alcohol and drug abuse.
      The present study examined differences in scores on the BIS/BAS scales between
      clinically referred drug addicts and alcoholics and healthy control subjects.
      Results showed that drug addicts had higher BAS scores than controls and this was
      particularly true for BAS drive and BAS fun seeking. No differences were observed
      between the alcoholics and the other two groups. This is the first time that a
      relation between heightened BAS and drug addicts is observed in a clinical
      sample. These findings provide partial support for Gray's personality theory,
      which predicts a relation between BAS and substance abuse.

PMID- 15964150
TI  - Clinical correlates of childhood abuse and neglect in substance dependents.
AB  - The aim of this study was to evaluate the prevalence of childhood abuse and
      neglect (CAN) in Turkish substance dependents and to investigate the relationship
      between CAN with axis I disorders, personality disorders and severity of
      depression and anxiety symptoms. Among 132 substance dependents, 56.1% met
      dichotomous criteria for some form of CAN. Current age was lower, whereas rate of
      suicide attempt, self-destructive behavior, divorce of parents, major depression,
      posttraumatic stress disorder (PTSD), lifetime specific phobia and personality
      disorders were higher in patients with history of CAN. Severity of depression and
      anxiety symptoms were also higher in group with CAN and number of abuse type was
      correlated with depression and anxiety scores. Lifetime major depression,
      lifetime PTSD, suicide attempt, self-destructive behavior and divorce of parents
      predicted CAN. The high rate of CAN found among Turkish substance dependents
      suggests that special attention must be given to identify CAN in this group.
      Findings of this study showed that there is a relationship between history of CAN
      and some axis I disorders, personality disorders and severity of depression and
      anxiety symptoms.

PMID- 15964151
TI  - Anxiety sensitivity: Concurrent associations with negative affect smoking motives
      and abstinence self-confidence among young adult smokers.
AB  - The present study evaluated the association between the lower-order facets of
      Anxiety Sensitivity construct (Physical, Mental Incapacitation and Social
      Concerns) and theoretically relevant cognitive-based smoking processes.
      Participants were 151 young adult daily smokers (63 females); mean number of
      cigarettes/day = 12.3 [S.D. = 5.6]). Both AS Physical and Mental Incapacitation
      Concerns were significantly associated with greater negative affect reduction
      smoking motives and lower levels of self-confidence in remaining abstinent from
      smoking when emotionally distressed. The observed effects were over and above the
      variance accounted for by nicotine dependence, smoking rate, and gender. Results
      are discussed in relation to better understanding cognitive-based smoking
      processes among individuals at heightened risk for panic psychopathology.

PMID- 15964152
TI  - Reasons for dropout from drug abuse treatment: symptoms, personality, and
      motivation.
AB  - Previous research has identified risk factors for early attrition from substance
      abuse treatment, but has not assessed reasons for dropout from the client's
      perspective. Interview and self-report assessment data were collected from 24
      clients who prematurely terminated outpatient treatment to evaluate their
      subjective reasons for dropping out and the association of these reasons with
      demographic and clinical variables. Items from scales indicating problems with
      client motivation or conflicts with program staff were the most commonly
      endorsed. The severity of participant's symptoms and logistical problems
      interfering with appointments were less commonly reported as reasons for dropping
      out. Demographic, substance abuse, and motivational stage indicators were
      infrequently associated with subjective reasons for dropout. In contrast,
      indicators of maladaptive personality functioning were strongly associated with
      many reasons for dropping out, especially concerns about privacy and boundary
      issues within the program. Results from this preliminary evaluation will guide
      the development of an instrument and intervention focused on dropout risk factors
      and treatment reengagement.

PMID- 15964153
TI  - Are dopaminergic genes involved in a predisposition to pathological aggression?
      Hypothesizing the importance of "super normal controls" in psychiatricgenetic
      research of complex behavioral disorders.
AB  - We hypothesize that pathological aggression, a complex behavioral disorder, in
      adolescents may in part involve polymorphisms of the dopaminergic system. While a
      number of neurotransmitter systems must be involved, due to polygenic
      inheritance, one major pathway should involve the dopaminergic system. Advances
      in our knowledge of the neurobiology of aggression and violence have given rise
      to rational pharmacological treatments for these behaviors. The main biological
      systems that are known to be involved are certain reward neurotransmitters
      including: serotonin, opioid peptides, gamma-aminobutyric acid, and the
      catecholamines (dopamine and norepinephrine). It is our notion that pathological
      aggressive behavior is in part similar mechanistically to other forms of
      impulsive behaviors such as pathological gambling. By analogy to drug dependence,
      it has been speculated that the underlying pathology in pathological gambling is
      a reduction in the sensitivity of the reward system. While studying pathological
      gamblers and controls during a guessing game using functional Magnetic Resonance
      Imaging, Reuter et al. observed a reduction of ventral striatal and ventromedial
      prefrontal activation in the pathological gamblers that were negatively
      correlated with gambling severity. Subsequently, linking hypo activation of these
      areas to disease severity. A positive correlation of both the dopamine D2
      receptor gene (DRD2) and the dopamine transporter gene (DAT1) polymorphisms were
      observed with pathological violence in adolescents in a blinded clinical trial.
      Thus, this and other cited work preliminary suggest a role for both the DRD2 and
      DAT genes in pathological aggressive behavior. We further hypothesize that follow
      up gene research in this area, albeit premature, resulting in confirmation of
      positive correlations with dopaminergic polymorphisms, and utilizing highly
      screened controls (eliminating any addictive, compulsive and impulsive behaviors
      in both proband and family) may have important ramifications in our young
      population.

PMID- 15964154
TI  - Enhancement of radiation effects by pXLG-mEndo in a lung carcinoma model.
AB  - PURPOSE: Endostatin is a potent antiangiogenesis protein with little or no
      toxicity that has potential to enhance radiotherapy. The major goal of this study
      was to evaluate the combination of radiation and endostatin gene therapy in a
      preclinical lung cancer model. METHODS: Plasmid pXLG-mEndo, constructed in our
      laboratory, includes the mouse endostatin gene cloned into the pWS4 vector. The
      kinetics of endostatin expression and efficacy of the pXLG-mEndo and radiation
      ((60)Co gamma-rays) combination was evaluated in the C57BL/6 mouse-Lewis lung
      carcinoma (LLC) model. The LLC cells were implanted s.c. and pXLG-mEndo was
      injected intratumorally 12-14 days later without any transfection agent; a dose
      of 10 Gy radiation was applied approximately 16 h thereafter. Some groups
      received each modality twice. Endostatin, vascular endothelial growth factor
      (VEGF), and transforming growth factor-beta1 (TGF-beta1) were quantified in
      plasma and tumors, and tumor vasculature was examined. RESULTS: Endostatin
      expression within LLC tumors peaked on Day 7 after pXLG-mEndo injection. Addition
      of radiation to pXLG-mEndo significantly enhanced the level of tumor endostatin
      compared with plasmid alone (p < 0.05). Tumor growth was significantly delayed in
      mice receiving pXLG-mEndo plus radiation compared with no treatment (p < 0.005),
      radiation (p < 0.05), and control plasmid (p < 0.05). The number of LLC tumor
      vessels was reduced after combined treatment (p < 0.05), and significant
      treatment-related changes were observed in both VEGF and TGF-beta1. CONCLUSIONS:
      The data demonstrate that delivery of endostatin by pXLG-mEndo as an adjuvant to
      radiation can significantly enhance the antitumor efficacy of radiotherapy in the
      LLC mouse tumor model and support further investigation of this unique
      combination therapy.

PMID- 15964155
TI  - Antibacterial activity of Ludwigia adscendens.
AB  - Methanolic extract of whole plants of Ludwigia adscendens was studied for its
      antibacterial activity. The extract showed a broad spectrum of antibacterial
      activity against all the bacteria tested except Stapylococcus aureus.

PMID- 15964156
TI  - Substance-dependent patients with and without social anxiety disorder: occurrence
      and clinical differences. A study of a consecutive sample of alcohol-dependent
      and poly-substance-dependent patients treated in two counties in Norway.
AB  - AIMS: (1) To identify clinically important differences between patients with and
      without social anxiety disorder (SAD) among alcohol-dependent and poly-substance
      dependent patients. (2) To explore if primary SAD is a predictor of alcohol
      dependency or poly-substance dependency when controlling for other Axes I and II
      disorders. METHODS: A consecutive sample of in- and outpatient alcohol-dependent
      (N = 146) and poly-substance-dependent patients (N = 114) from public treatment
      programmes in two catchment areas was assessed by personal interview, the
      Composite International Diagnostic Interview and the Millon Clinical Multiaxial
      Inventory. RESULTS: The frequency of current SAD was 42%; SAD was significantly
      more frequent among poly-substance-dependent patients (51%) than among alcohol
      dependent patients (34%). Patients with SAD do not represent a distinct clinical
      subgroup, but the occurrence of SAD is combined with the occurrence of other
      anxiety disorders, affective disorders and personality disorders in both
      substance groups. The analysis showed a trend towards primary SAD as a predictor
      for developing poly-substance dependency. CONCLUSIONS: Patients with SAD in both
      substance groups exhibited more comorbid Axis I and II disorders. They may need
      specific psychiatric treatment for such disorders in addition to treatment for
      SAD. Treatment of primary SAD could be a target for preventing poly-substance
      dependency in young populations.

PMID- 15964157
TI  - Functional mapping of the bovine Doppel gene promoter region.
AB  - The PRND gene encodes Doppel (Dpl), a protein that is strongly expressed in
      testis and at much lower levels in other tissues. Despite the recent discovery of
      Dpl involvement in spermiogenesis and in apoptotic death of cerebellar neurons,
      respectively in wild type and transgenic mice, the physiological role of this
      prion-like protein remains unknown. To better understand which factors may
      contribute to the modulation of PRND activity, a study of the bovine promoter
      region was performed. First, the transcription start site of PRND mRNA was
      identified using an innovative fluorescently labelled oligonucleotide extension
      (FLOE) method. The initiation site mapped 129 nt upstream of the protein coding
      sequence and represents a refinement of a previous assignment based on RACE.
      Second, deletion mutants of the 4530 nt encompassing 2704 nt 5' of the bovine
      PRND, exon 1, intron 1, and the first 6 nt of exon 2, have been investigated with
      CAT-reporter assays in order to identify critical elements for the activation of
      the gene. The results showed that the region -323/+32 (+1 is the transcription
      start site mapped by FLOE) represents the promoter region and contains positive
      cis-acting elements (CCAAT and E box) confirming previous reports with the mouse
      gene. Additional regulatory elements, including binding sites for repressor
      molecules, have been identified upstream of that region and in the first portion
      of intron 1, suggesting a complex tissue-specific regulation of Doppel gene
      expression.

PMID- 15964158
TI  - Virological and molecular characterization of a mammalian orthoreovirus type 3
      strain isolated from a dog in Italy.
AB  - A mammalian orthoreovirus (MRV) strain was isolated from a pup with fatal
      diarrhea, which had a concurrent infection by canine parvovirus type 2. The
      reovirus isolate showed an atypical hemagglutination pattern and a retarded
      electrophoretic mobility of the S1 segment, which is characteristic of MRV type 3
      (MRV-3). Assignment of the isolated virus to MRV-3 was confirmed by type-specific
      RT-PCR assays, targeting the S1 gene, and by subsequent sequence analysis of the
      PCR product. By phylogeny based on the S1 gene of several MRVs, the isolate fell
      into lineage E, along with the murine strain T3C9/61 and the bovine strains
      T3C18/61 and T3C31/59. Conversely, L1 sequences were found to segregate
      regardless of the viral type. A total of 110 fecal samples, 56 nasal and 31
      ocular swabs from dogs with diarrhea or nasal/ocular discharge were tested by a
      nested-PCR assay specific for reoviruses, and no sample was found to contain MRV
      RNA, a finding that is apparently in contrast with the seroprevalence (25.77%)
      observed in dogs.

PMID- 15964159
TI  - Embryotoxicity of the nitric oxide donor sodium nitroprusside in preimplantation
      bovine embryos in vitro.
AB  - Many early pregnancy complications are associated with an imbalance in pro- and
      anti-inflammatory cytokines, resulting in alterations in nitric oxide (NO)
      profile. Since very little is known about the modus operandi of this free radical
      in early embryos, this study characterised NO embryotoxicity in terms of bovine
      embryo development and metabolism. Embryos were generated by in vitro maturation
      and fertilisation of oocytes aspirated from abattoir-derived ovaries. Zygote to
      blastocyst rates were measured in SOFaaBSA in the presence and absence of the NO
      donor sodium nitroprusside (SNP) over the 0-50 microM range (n=10 per group).
      Since concentrations <10 microM SNP depressed blastocyst rate, blastocyst cell
      numbers (determined by bisbenzimide staining; n=22 and 20), glucose, pyruvate,
      lactate (measured ultramicrofluorometrically) and amino acid profiles (quantified
      by HPLC; n=28 and 23) were assessed at 0 and 10 microM SNP. SNP depressed cell
      numbers, reduced pyruvate and glucose uptake, perturbed quantitative tyrosine,
      threonine, phenylalanine, lysine, glycine, tryptophan, methionine and valine
      profiles, and decreased retention into the negative range (P<0.05). Qualitative
      asparagine and lysine profiles were affected by SNP, while proportional amino
      acid production and consumption were increased and decreased, respectively
      (P<0.05). These findings indicate that SNP (presumably through increases in NO
      profile): (i) fails to improve bovine embryo development in vitro, (ii) exerts
      toxic effects, likely through ATP starvation induced by cytochrome c oxidase
      (oxidative phosphorylation) and glyceraldehyde-3-phosphate dehydrogenase
      (glycolysis) inhibition, and (iii) may affect albumin endocytosis/hydrolysis or
      protein biosynthesis, rather than causing a loss of intracellular amino acids or
      simply depressing their metabolism.

PMID- 15964160
TI  - Conjugated estrogen/progestagen versus tibolone hormone replacement therapy in
      postmenopausal women: Effects on carbohydrate metabolism and serum sex hormone
      binding globulin.
AB  - OBJECTIVE: To study the effects of different types of continuous hormone
      replacement therapy on carbohydrate metabolism. METHOD: Postmenopausal women were
      treated with conjugated estrogens, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5
      mg (CEE/MPA) or tibolone 2.5 mg daily for 13 28-day cycles. Serum glucose and
      insulin were measured before and during a 75 g oral glucose tolerance test (OGTT)
      at baseline and after 3, 6 and 13 cycles and areas under the curve (AUC) were
      calculated. Sex hormone-binding globulin (SHBG) was measured as an additional
      marker of nutritional and insulin status. RESULTS: Neither CEE/MPA 2.5mg nor
      tibolone had any effects on carbohydrate metabolism while AUC(insulin),
      AUC(glucose) and also body mass index (BMI) increased after 13 cycles of
      treatment in the CEE/MPA 5 mg group. SHBG increased significantly during CEE/MPA
      treatment and decreased significantly during treatment with tibolone. The effects
      on SHBG were less pronounced in the CEE/MPA 5mg group. Pretreatment SHBG showed
      significant negative correlations to BMI and to variables that may reflect a
      certain degree of insulin resistance, the most pronounced being fasting glucose.
      Changes in SHBG during treatment with tibolone were negatively correlated to
      pretreatment SHBG and positively to BMI, AUC(insulin) and fasting insulin
      resistance index, while no such correlations were found in the CEE/MPA groups.
      There were no correlations between changes in AUC(insulin) and AUC(glucose) on
      one hand and basal variables or treatment SHBG on the other in the CEE/MPA
      groups. CONCLUSION: The effects of tibolone and CEE/MPA on carbohydrate
      metabolism were considered to have clinical significance only for CEE/MPA 5mg,
      indicating a less favourable role of the higher progestagen dose. The results
      further support the important role of metabolic and insulin status in the
      physiological regulation of SHBG and also indicate that the suppressive effect of
      tibolone on circulating SHBG is mainly depends on pretreatment SHBG levels. SHBG
      does not reflect changes in carbohydrate metabolism during CEE/MPA treatment.

PMID- 15964161
TI  - Mexican plants with hypoglycaemic effect used in the treatment of diabetes.
AB  - Diabetes mellitus is a syndrome which affects more and more people in all
      countries over the world. In Mexico, it is commonly treated with herbal extracts.
      Such treatment may be of considerable benefit especially during the early stages
      of the illness. In this review, we discuss species commonly used in Mexico in the
      treatment of diabetes. A total of 306 species have records of a popular use in
      the treatment of this syndrome in Mexico. Seven of these species--Cecropia
      obtusifolia Bertol. (Cecropiaceae), Equisetum myriochaetum Schlecht & Cham
      (Equisetaceae), Acosmium panamense (Benth.) Yacolev (Fabaceae), Cucurbita
      ficifolia Bouche (Cucurbitaceae), Agarista mexicana (Hemsl.) Judd. (Ericaeae),
      Brickellia veronicaefolia (Kunth) A. Gray (Asteraceae), Parmentiera aculeata
      (Kunth) Seem. (Bignoniaceae)--are discussed in greater detail, highlighting our
      current knowledge about these botanicals, but also the enormous gaps in our
      knowledge, most notably as it relates to the species' toxicology, the
      pharmacokinetics of its active constituents and their metabolism.

PMID- 15964162
TI  - Antiradical and antioxidant activity of total anthocyanins from Perilla
      pankinensis decne.
AB  - The purpose of this work comprise the assessment of the antioxidant activity of
      total anthocyanins from Perilla pankinensis samples (TAPP) by different
      analytical methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging,
      total antioxidant activity, total reducing activity, superoxide anion radical
      scavenging, hydrogen peroxide scavenging and metal chelating activities. Total
      antioxidant activity was measured according to ferric thiocyanate method. alpha
      Tocopherol and trolox, which water-soluble analogue of tocopherol were used as
      references antioxidant compounds. At the concentrations of 30 and 45 microg/mL,
      TAPP showed 91.9 and 96.4% inhibition on lipid peroxidation of linoleic acid
      emulsion, respectively. In comparison, 45 microg/mL of standard antioxidant such
      as alpha-tocopherol and trolox exhibited 88.8 and 86.2% inhibition on
      peroxidation of linoleic acid emulsion, respectively. In addition, TAPP have
      found effective on DPPH scavenging, superoxide anion radical and hydrogen
      peroxide scavenging, total reducing power and metal chelating on ferrous ions
      activities. Also, these various antioxidant effects were compared to alpha
      tocopherol and trolox.

PMID- 15964163
TI  - Inhibition of rat vascular smooth muscle cell proliferation by extract of
      Ligusticum chuanxiong and Angelica sinensis.
AB  - Ligusticum chuanxiong (LC) and Angelica sinensis (AS) have been widely used as
      traditional Chinese medicine to treat some pathological settings such as
      atherosclerosis and hypertension. The aim of this paper is to determine the
      effects of the extract of LC and AS (ELCAS) on serum-induced vascular smooth
      muscle cell (VSMC) proliferation, cell cycle and nitric oxide production. The
      results show that ELCAS significantly inhibited proliferation and protein
      synthesis of VSMC in a dose and time dependent manner. The cell population
      assessed by flow cytometry in the G(0)/G(1) phase increased 74% versus 79.8%,
      concomitant with a decrease in the S phase, 7.4% versus 4.2%, for control versus
      ELCAS (300 microg/ml). On the other hand, ELCAS significantly increased nitric
      oxide production of VSMC. The data suggest that ELCAS markedly inhibited VSMC
      proliferation by arresting G(1) to S progression, which may be associated with
      nitric oxide production.

PMID- 15964164
TI  - Percutaneous radiofrequency treatment of osteoid osteoma using cool-tip
      electrodes.
AB  - OBJECTIVES: To report our experience with percutaneous cool-tip radiofrequency
      ablation of osteoid osteomas and to evaluate clinical outcome. METHODS AND
      MATERIAL: Forty-one patients with clinically and radiologically suspected osteoid
      osteoma were seen over a 48-month period (27 males and 14 females with a mean age
      of 18.7 years; range 5-43 years). Thirty-eight patients were treated by computed
      tomography (CT)-guided percutaneous radiofrequency ablation. The procedure was
      performed under regional or general anaesthesia. After location of the nidus, a
      14G-bone biopsy needle is introduced into the nidus. Sampling is performed with a
      17G-bone biopsy needle using a coaxial technique. The radiofrequency needle with
      a 10mm active tip (cool-tip) is inserted through the biopsy needle and is
      connected to the radiofrequency generator for 6-8 min. RESULTS: Primary success
      was obtained in 37 patients (97%) with a 100% secondary success rate. All
      patients are currently pain-free. No major complications occurred. Patients could
      resume unrestricted normal activity within 24 h. CONCLUSIONS: Percutaneous
      radiofrequency ablation of osteoid osteomas is an efficient and safe method that
      can be considered the procedure of choice for most cases.

PMID- 15964165
TI  - Carotid stenosis measurement on colour Doppler ultrasound: agreement of ECST,
      NASCET and CCA methods applied to ultrasound with intra-arterial angiographic
      stenosis measurement.
AB  - PURPOSE: Carotid stenosis is usually determined on Doppler ultrasound from
      velocity readings. We wondered if angiography-style stenosis measurements applied
      to ultrasound images improved accuracy over velocity readings alone, and if so,
      which measure correlated best with angiography. MATERIALS AND METHODS: We studied
      prospectively patients undergoing colour Doppler ultrasound (CDU) for TIA or
      minor stroke. Those with 50%+ symptomatic internal carotid artery (ICA) stenosis
      had intra-arterial angiography (IAA). We measured peak systolic ICA velocity, and
      from the ultrasound image, the minimal residual lumen, the original lumen (ECST),
      ICA diameter distal (NASCET) and CCA diameter proximal (CCA method) to the
      stenosis. The IAAs were measured by ECST, NASCET and CCA methods also, blind to
      CDU. RESULTS: Amongst 164 patients (328 arteries), on CDU the ECST, NASCET and
      CCA stenosis measures were similarly related to each other (ECST = 0.54 NASCET +
      46) as on IAA (ECST = 0.6 NASCET + 40). Agreement between CDU- and IAA-measured
      stenosis was similar for ECST (r = 0.51), and CCA (r = 0.48) methods, and
      slightly worse for NASCET (r = 0.41). Adding IAA-style stenosis to the peak
      systolic ICA velocity did not improve agreement with IAA over peak systolic
      velocity alone. CONCLUSION: Angiography-style stenosis measures have similar
      inter-relationships when applied to CDU, but do not improve accuracy of
      ultrasound over peak systolic ICA velocity alone.

PMID- 15964166
TI  - Stimulation of implant fixation by parathyroid hormone (1-34)-A histomorphometric
      comparison of PMMA cement and stainless steel.
AB  - Whereas continuous exposure to PTH results in bone resorption, PTH administration
      at intermittent doses results in bone formation by increasing osteoblast number
      and activity. PTH leads to faster fracture repair and better fixation of
      orthopaedic implants in animal models. The present study evaluates if PTH is able
      to increase the contact surface between bone and implant and whether the effect
      of PTH is dependent on implant material characteristics. The implants were made
      as rods, either of stainless steel or Palacos R bone-cement. The steel rods had a
      surface roughness of R(a) 0.1 microm and the cement rods R(a) 2.2 microm. In 40
      adult male rats, one cement rod was inserted in the left tibia and one steel rod
      in the right tibia. After implantation, the rats were divided into groups by
      random. One group was injected three times a week with human PTH (1-34) at a dose
      of 60 microg/kg BW/injection. The second group was injected with the vehicle
      only. Both groups were then divided into groups for 2 and 4 weeks time till
      tibial harvest. The tibial segments around the hole of the rods were then
      prepared by standard histological techniques. The linear tissue surfaces, that
      had been in contact with the surface of the rod, were analyzed in a blind
      fashion. PTH increased the bone contact fraction compared with the vehicle in the
      steel group from 7.4 (SD 7.6) to 21.1 (SD 10.7) % after 2 weeks and from 9.8 (SD
      8.1) to 47.1 (SD 13.3) % after 4 weeks. In the cement group PTH increased the
      contact index again compared with the vehicle from 7.8 (SD 10.2) to 53.6 (SD
      26.3) % already after 2 weeks and from 14.3 (SD 15) to 65.6 (SD 15.7) % after 4
      weeks. The bone trabeculae adjacent to the implant had become fewer and thicker
      after the treatment with PTH (1-34), with an increase of the bone mass in the
      area next to the bone-implant-interface. The earlier onset of PTH effects in the
      rougher cement group suggests that intermittent PTH treatment might lead to an
      increased micro-interlock between implant and bone, and might therefore be
      considered as a possible drug to enhance incorporation of orthopedic implants.

PMID- 15964167
TI  - Biological and mechanical changes of the bone graft-cement interface after
      impaction allografting.
AB  - In impaction allografting, the host bone interface may consist of morsellized
      allograft alone or as a composite with bone cement. The objective of this study
      was to investigate the temporal changes in the interface for these two materials
      in a rat bone chamber model. To simulate the impaired endosteal circulation after
      impaction allografting, bone chambers were tightened bilaterally to the endosteal
      surfaces of proximal tibiae of mature rats and filled with pure allograft or
      cement/allograft composite. The cement/allograft composite-host bone interface
      strength was significantly higher at 3 weeks and was higher than the allograft
      construct failure strength. Limited allograft, but extensive periosteal
      remodeling, was observed at 3 weeks which resulted in a significantly increased
      cortical porosity and cortical thickness. The allograft porosity decreased
      significantly at 6 weeks indicating extensive remodeling of the allograft bone.
      Little or no remodeling of the allograft particles in the cement was found. At 6
      weeks a new medullary canal was formed, and the endosteal cortex was partially
      absorbed. Endosteal absorption resulting in medullary canal widening in revision
      THR may be responsible for clinically unstable stems after impaction
      allografting.

PMID- 15964168
TI  - A comparative study of the antioxidant/prooxidant activities of eugenol and
      isoeugenol with various concentrations and oxidation conditions.
AB  - Eugenol (compound in , 4-allyl-2-methyoxyphenol) and isoeugenol (compound in , 4
      propenyl-2-methoxyphenol), both used as a flavor agent in cosmetic and food
      products, have both prooxidant and antioxidant activities. Their adverse effects
      such as allergic and inflammatory reaction may be due to their prooxidant
      activity. To clarify the mechanisms of their cytotoxicity and the factors
      affecting their antioxidant/prooxidant activities, we investigated the
      cytotoxicity, ROS production, and cellular glutathione (GSH) levels induced by
      eugenol and isoeugenol in a human submandibular cell line. The cytotoxicity (MTT
      method) of eugenol was 1 order of magnitude lower than that of isoeugenol (CC50:
      eugenol, 0.395 mM; isoeugenol, 0.0523 mM); and ROS production (CDF staining) was
      induced significantly by isoeugenol, but not by eugenol. Under treatment with
      H2O2 (100 microM) plus horseradish peroxidase (1 microg/ml) for 30 min or with
      visible light irradiation for 5 min, eugenol caused biphasic ROS production
      characterized by enhanced at lower eugenol concentrations (5-10 microM) and
      decreased at higher concentrations (500 microM). In contrast, isoeugenol enhanced
      ROS production over a wide range of concentrations (5-500 microM). Isoeugenol at
      1000 microM significantly reduced GSH levels compared with eugenol at the same
      concentration. The high cytotoxicity of isoeugenol may be attributed to its
      induction of high ROS production and low GSH levels, possibly as a result of
      benzyl radical formation. In contrast, the cytotoxicity of eugenol is likely to
      be mediated by ROS-independent mechanisms, possibly involving phenoxyl radicals
      and/or eugenol quinone methide.

PMID- 15964169
TI  - Modulation of peroxisome proliferator-activated receptors (PPARs) by PPAR(alpha)-
      and PPAR(gamma)-specific ligands and by 17beta-estradiol in isolated zebrafish
      hepatocytes.
AB  - Peroxisome proliferation is a phenomenon occurring when responsive animals are
      exposed to certain compounds so-called peroxisome proliferators and is regulated
      through a nuclear receptor named peroxisome proliferator-activated receptor
      (PPAR). PPAR family members exhibit a strong binding affinity for both saturated
      and unsaturated fatty acids. Activators of PPAR(alpha) include a variety of
      endogenously present fatty acids, leukotrienes and hydroxyeicosatetraenoic acids
      (HETEs) and clinically used drugs, such as fibrates. PPAR(beta) activators
      include fatty acids, prostaglandin A2 (PGA2) and prostacyclin (PGI2). PPAR(gamma)
      is the most selective receptor and, among others, 15-deoxy-Delta(12,14)
      prostaglandin J2 (PGJ2) has been described to be a PPAR(gamma)-specific ligand.
      The aim of the present study was to determine if known PPAR(alpha) and
      PPAR(gamma) ligands were able to alter the expression of these subtypes in an in
      vitro model of zebrafish primary hepatocyte culture. With this purpose, a
      PPAR(alpha) specific ligand (8S-HETE), a PPARgamma specific ligand (PGJ) and a
      peroxisome proliferator of the fibrate class (clofibrate) were selected. In
      addition, the female hormone 17beta-estradiol was also used as it is known to
      interact with PPARs. After cell exposure for 24 h, cells were
      immunohistochemically stained for both PPARs and immunolabeling was quantified as
      percentage of positive nuclei and cells. Levels of expression of PPARs were also
      measured by image analysis as grey level per cell. Expression was induced for
      both PPAR(alpha) and PPAR(gamma) by clofibrate (at 0.5 mM for PPAR(alpha) and at
      1 and 2 mM for PPAR(gamma)), by HETE (1 microM), and by PGJ2 (0.3 and 1 microM
      for PPAR(alpha) and 0.3 microM for PPAR(gamma)). Expression of PPARgamma was also
      induced at 10 microM by 17beta-estradiol. The percentage of PPAR(alpha) positive
      nuclei increased significantly at 1 microM HETE and the percentage of PPAR(gamma)
      positive cells decreased at 10 microM 17beta-estradiol. As a conclusion,
      clofibrate, HETE and PGJ2 are able to induce expression of both PPAR(alpha) and
      PPAR(gamma) in zebrafish primary hepatocyte cultures. Further studies are needed
      to identify how the expression of different PPAR subtypes is regulated and to
      elucidate the implication of PPAR subtypes in zebrafish cell functions.

PMID- 15964170
TI  - The importance of (early) folate status to primary and secondary coronary artery
      disease prevention.
AB  - Folate, methionine, betaine, choline, zinc and Vitamins B(12), B(6) and B(2) are
      involved in one-carbon metabolism, which includes S-adenosylmethionine (SAM)
      substrated methylation. Inadequate enzyme activities and imbalances of substrates
      and cofactors in one-carbon metabolism, together referred to as the
      'methyldietary' constituents, may cause homocysteine and S-adenosylhomocysteine
      accumulation. Hyperhomocysteinemia is associated with many disorders including
      coronary artery disease (CAD). CAD at adult age is also associated with low birth
      weight-induced 'programming', which prepares for unfavorable postpartum
      conditions and carries the potential of transgenerational transmission. CAD risks
      of hyperhomocysteinemia and 'programming' might find a common biochemical basis
      in epigenetics, which, among others, operates via SAM-substrated methylation of
      DNA and histones. Folic acid-responsive global and locus-specific hypomethylation
      were found in hyperhomocysteinemia and CAD. Currently, there is no hard evidence
      that folic acid supplementation of CAD patients is beneficial or that improved
      folate status in pregnancy prevents CAD in the offspring at adult age. The folate
      RDA as derived from CAD primary prevention might require embracement of the
      assumption that 'what nutritional measures are best for CAD patients are most
      probably best for the general population'. We have no knowledge on the optimal
      'methyldiet' balance on which our genome has become adapted during millions of
      years of evolution and on which our genome consequently functions best. More
      insight may derive from the study of methyldietary constituents and soft
      endpoints such as plasma homocysteine and gene methylation, in healthy, pregnant
      and non-pregnant, subjects and CAD patients and in populations with high and low
      CAD risks and those consuming diets more closely related to our ancient diet.
      Folic acid supplementation is obviously unnecessary at sufficient intake of
      naturally occurring folates, implying that continuing efforts should aim at
      meeting the recommendations by making the right choice of food products, that are
      either or not folate-enriched by genetic modification.

PMID- 15964171
TI  - Polyglutamine-expanded ataxin-7 activates mitochondrial apoptotic pathway of
      cerebellar neurons by upregulating Bax and downregulating Bcl-x(L).
AB  - Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative
      disorder caused by polyglutamine-expanded ataxin-7. In the present investigation,
      we expressed disease-causing mutant ataxin-7-Q75 in the primary neuronal culture
      of cerebellum with the aid of recombinant adenoviruses. Subsequently, this in
      vitro cellular model of SCA7 was used to study the molecular mechanism by which
      mutant ataxin-7-Q75 induces neuronal death. TUNEL staining studies indicated that
      polyglutamine-expanded ataxin-7-Q75 caused apoptotic cell death of cultured
      cerebellar neurons. Mutant ataxin-7-Q75 induced the formation of active caspase-3
      and caspase-9 without activating caspase-8. Polyglutamine-expanded ataxin-7-Q75
      promoted the release of apoptogenic cytochrome-c and Smac from mitochondria,
      which was preceded by the downregulation of Bcl-x(L) protein and upregulation of
      Bax protein expression in cultured cerebellar neurons. Further real-time TaqMan
      RT-PCR assays showed that mutant ataxin-7-Q75 upregulated Bax mRNA level and
      downregulated Bcl-x(L) mRNA expression in the primary neuronal culture of
      cerebellum. The present study provides the evidence that polyglutamine-expanded
      ataxin-7-Q75 activates mitochondria-mediated apoptotic cascade and induces
      neuronal death by upregulating Bax expression and downregulating Bcl-x(L)
      expression of cerebellar neurons.

PMID- 15964172
TI  - The relationship of bone marrow edema pattern in the mandibular condyle with
      joint pain in patients with temporomandibular joint disorders: longitudinal study
      with MR imaging.
AB  - The purpose of this study was to investigate the course of bone marrow edema
      pattern (decreased signal intensity on T1- or proton-density-weighted images and
      increased signal intensity on T2-weighted fat-suppressed images) in the
      mandibular condyle after improvement in clinical symptoms, and to clarify its
      relationship with temporomandibular joint (TMJ) pain. This study was based on 14
      joints of 11 patients (all female, mean age 37.5 years) with TMJ disorders
      showing condylar bone marrow edema pattern on initial magnetic resonance (MR)
      images. All joints were re-evaluated clinically and using MR images after relief
      of joint pain following arthrocentesis combined with non-surgical treatment. The
      time interval between the initial and follow-up MR images ranged from 14 to 27
      months (mean 17 months). Of the 14 joints, 4 joints (28.6%) showed a normal bone
      marrow signal, whereas 10 joints (71.4%) showed persistent bone marrow edema
      pattern on follow-up MR images (P = 0.125). Therefore, the reduction in TMJ pain
      did not correlate with resolution of bone marrow edema pattern in most joints.
      The results of this study suggest that the bone marrow edema pattern in the
      mandibular condyle does not always contribute to the occurrence of joint pain in
      patients with TMJ disorders.

PMID- 15964173
TI  - Calcifications in a clear cell mucoepidermoid carcinoma of the hard palate.
AB  - Although calcification is a common finding in inflammatory salivary gland
      disorders, salivary gland tumour rarely shows calcifications. A case of clear
      cell mucoepidermoid carcinoma (MEC) of the hard palate with extensive
      intratumoural calcifications visible on computed tomography (CT) scans and
      histologic sections is described. The calcification in the salivary gland tumour
      of the palate recognized by a CT scan should be considered in the differential
      diagnosis of a MEC. The mechanism of the intratumoural calcification in our case
      is speculated to be a result of a secretory function of the tumour cells.

PMID- 15964175
TI  - Social support and three-year symptom and admission outcomes for first episode
      psychosis.
AB  - This paper presents the first published findings examining the relationship of
      social support to three-year symptom outcome and hospitalizations for a group of
      first episode patients with psychotic disorders. Social support was measured
      using items from the provider version of the Wisconsin Quality of Life Scale as
      assessed at the time of initiation of treatment for 113 patients. Outcome was
      assessed by level of positive and negative symptoms at three-year follow-up and
      number of psychiatric admissions during those three years. Higher levels of
      social support were found to correlate with lower levels of positive symptoms and
      few hospitalizations at follow-up. The relationship of social support to follow
      up symptoms and hospitalization was independent of other potential predictors
      such as gender, age, premorbid adjustment and duration of untreated illness.

PMID- 15964176
TI  - Serum lipid profiles and schizophrenia: effects of conventional or atypical
      antipsychotic drugs in Taiwan.
AB  - This study investigated the relationships between serum lipid profiles and
      schizophrenia and the effects of conventional or atypical antipsychotic drugs on
      serum lipid profiles. During a 1-year period, fasting blood samples for serum
      lipid profiles were collected from 126 schizophrenic patients and 59 healthy
      control subjects. The serum lipid profiles were detected by enzymatic
      determination. Patients were assessed for disease severity at baseline and
      endpoint at 3 weeks using the Positive and Negative Syndrome Scale. At baseline,
      patients with acute-phase schizophrenia had lower high-density lipoprotein (HDL)
      levels, higher low-density lipoprotein (LDL) levels, and higher ratios of total
      cholesterol/high-density lipoprotein (TC/HDL) and LDL/HDL than healthy control
      subjects. At endpoint, after a 3-week treatment with antipsychotics, the blood
      samples of the 97 schizophrenic patients were assessed again. Responders to
      antipsychotic treatment (n = 68) but not nonresponders (n = 29) had significantly
      increased TC, triglyceride (TG), and very low-density lipoprotein (VLDL) levels
      and decreased ratio of LDL/HDL. Experimental findings also showed significantly
      increased TC, TG, HDL, and VLDL levels and decreased ratio of LDL/HDL in
      responders taking atypical antipsychotic drugs (n = 32), but not in patients
      treated with conventional antipsychotic drugs (n = 36). In conclusion, this study
      identified strong associations between dyslipidemia and acute-phase schizophrenia
      and dyslipidemia and responders taking atypical antipsychotics; both associations
      would increase the risk of developing diabetes and coronary heart disease.

PMID- 15964177
TI  - Ten year longitudinal study of neuropsychological functioning subsequent to a
      first episode of schizophrenia.
AB  - We previously reported relative stability in neuropsychological functions over a
      4- to 5-year period after the onset of a first episode of schizophrenia, with
      patients demonstrating less improvement than controls on some functions [Hoff,
      A.L., Sakuma, M., Wieneke, M., Horon, R., Kushner, M., DeLisi, L.E., 1999. A
      longitudinal follow-up study of neuropsychological functioning subsequent to a
      first-episode of schizophrenia. American Journal of Psychiatry 156, 1336-1341.].
      The current study was conducted to extend follow-up evaluations through 10 years
      of illness to determine whether neuropsychological functions remain stable or
      deteriorate over a longer time period. Twenty-one first episode patients and 8
      controls were re-evaluated 10 years after an initial evaluation on
      neuropsychological and clinical measures. Repeated measures analyses demonstrated
      no differences between patients and controls in degree of change over this time
      period nor was change in symptoms reliably associated with improvement or
      deterioration in cognitive abilities. However, baseline level of cognitive
      functioning was correlated with the degree of change. Thus, when the baseline
      level of functioning was controlled for in the analyses, less or lack of
      improvement was seen in the patients compared with controls in verbal
      intellectual functioning, delayed verbal and nonverbal recall, and cognitive
      inhibition (Stroop Color Word Test). In no test did patients deteriorate
      significantly more than controls. We conclude that most first episode patients
      have had considerable cognitive decline by the time of their first
      hospitalization and that it remains relatively stable through at least 10 years
      of illness. Most cognitive change takes place early in this illness, prior to the
      first hospitalization, but its exact timing still remains unknown.

PMID- 15964178
TI  - Comments on risk for schizophrenia.
AB  - Recent developments have significantly furthered understanding of genetic and
      environmental factors affecting risk for schizophrenia. Environmental effects,
      such as immigration, living in a city, and substance abuse have been found to be
      associated with later schizophrenia. Although the highest risk for schizophrenia
      is still having a monozygotic twin with schizophrenia (50%), the candidate genes
      claimed to be associated to date only yield a very small excess risk and all of
      these effects (environmental and genetics) increase the risk for schizophrenia by
      only 2-3 fold. Thus, given the low prevalence of the disorder in the general
      population (0.5-1%), they are not practical in predicting future illness. One
      possible strategy to make the currently known risk factors for schizophrenia more
      useful clinically is based on findings indicating that many of the genetic and
      environmental risks cited above are not specific for schizophrenia, but increase
      risk for psychopathology in general. As up to 50% of the general population will
      be affected during their lifetime by a condition defined in DSM IV as
      psychopathology, due to this much higher base rate, factors increasing risk by 2
      3 fold might become clinically relevant.

PMID- 15964179
TI  - Development of a simple method for the preparation of a silica gel based
      controlled delivery system with a high drug content.
AB  - Silica gel was used as core particles to design a simple preparation for
      controlled delivery system with a high drug content. Drug loading was carried out
      by immersing the silica gel in a pre-heated drug solution or suspension. HPLC,
      SEM, DSC, PXRD analysis and N2 adsorption studies evaluated the drug-loading
      process. In the next step, the drug-loaded silica gel was coated with
      hydroxypropyl methylcellulose (HPMC) and an aqueous dispersion of ethylcellulose
      (Aquacoat) to control the drug release. The release profile was determined using
      a dissolution test. The results showed that silica gel could adsorb great
      quantities of the drug, up to about 450 mg/g, by repetition of the loading
      process. Evaluation of the drug-loading process indicates that drug deposition in
      the pores occurs during the loading process and the drug-loading efficacy is
      strongly related to the drug solubility. On the other hand, the dissolution test
      showed that the drug release could be controlled by polymer coating the drug
      loaded silica gel. An HPMC undercoating effectively suppresses the drug release,
      as it smoothes the drug-loaded core surface and aids in the formation of a
      continuous Aquacoat coating film. The floating property was also observed during
      the dissolution test.

PMID- 15964180
TI  - Prevalence of tuberculosis in small pulmonary nodules obtained by video-assisted
      thoracoscopic surgery.
AB  - The prevalence of tuberculosis in small solitary lesions of the lung obtained by
      video-assisted thoracoscopic surgery (VATS) is still unclear. Of 103 lung lesions
      resected by VATS in 98 patients (47 men, 51 women), 19 were identified
      macroscopically as inflammatory changes, 78 were neoplastic, and 6 were
      undefined. Presumptive diagnosis based on microscopic analysis of fresh specimen
      smears treated with Papanicolaou stain was performed in 19 lesions. Of these, 11
      lesions had epithelioid cells, granulomas with caseous necrosis and Langerhans
      type giant cells. The 6 undefined lesions were non-inflammatory benign changes.
      Isolation and identification of tuberculosis were based on microscopic findings
      of fresh material smears and sections of fixed specimens stained with Ziehl
      Neelsen's dye, cultivation using egg-based Ogawa medium, and in situ
      hybridization between polymerase chain reaction (PCR) products of each of the 11
      lesions and specific DNA sequences for Mycobacterium tuberculosis, M. avium, and
      M. intracellulare. Of these 11 lesions, M. tuberculosis was confirmed in one
      (0.96%) by PCR and M. avium was confirmed in four by culture and PCR. Of the 78
      malignant lesions, final pathologies were primary lung cancer (n=59, 70.2%) and
      pulmonary metastatic cancer (n=19, 22.6%). The most frequent primary malignant
      cancer was adenocarcinoma, which was found in 19 men and 28 women in the present
      study. Eight lesions in 8 men were squamous cell carcinomas. The results of the
      present study suggested that even though the prevalence of lung tuberculosis is
      low, attention should be paid to the presence of M. tuberculosis in specimens
      obtained by VATS.

PMID- 15964181
TI  - Characterization of spent AA household alkaline batteries.
AB  - The aim of this work is identification of the structural components of actual
      domestic spent alkaline AA batteries, as well as quantification of some of their
      characteristics. Weight, humidity, ash content, zinc and zinc oxide on anode,
      manganese on cathode and other metals, potassium hydroxide on the internal
      components and heating values for papers, anode and cathode were determined in
      several batteries. As expected, cathode, anode and the steel can container are
      the main contributors to the 23.5 g average weight of the batteries. Cathode is
      also the major contributor to the positive heating value of the batteries as well
      as to the heavy metals content. Mercury was detected in very low levels in these
      mercury-free batteries. Zinc and zinc oxide amounts in the anodes are highly
      variable. Results obtained were compared to information on alkaline batteries in
      the literature from 1993 to 1995; and a positive evolution in their manufacture
      is readily apparent. Data from the producer of batteries shows some small
      discrepancies relative to the results of this experimental work.

PMID- 15964182
TI  - SERMs in chemoprevention of breast cancer.
AB  - Selective estrogen receptor modulators (SERMs) play a key role in breast cancer
      chemoprevention. Tamoxifen has been shown to reduce breast cancer incidence by 30
      40% in at-risk subjects in large phase III trials. However, toxicity may be a
      limiting factor. Thus, different strategies are being pursued to improve the
      risk: benefit ratio of using these compounds in chemoprevention. Firstly, the
      second generation SERM raloxifene is currently undergoing evaluation in
      comparison with tamoxifen in a large phase III trial. Also, lower doses of
      tamoxifen are being assessed in phase II-III trials. In addition, the combination
      of hormone replacement therapy (HRT) or aromatase inhibitors and tamoxifen at low
      doses may reduce the risks while retaining the benefits of either agents.
      Finally, new agents that interfere with the onset of ER-negative breast cancer
      are being sought for combination chemoprevention since almost a third of breast
      cancers will not be sensitive to hormonal modulation.

PMID- 15964183
TI  - Is there a future in psychosocial predictive factors in breast cancer?

PMID- 15964184
TI  - Cyclooxygenase-2 expression predicts survival in malignant pleural mesothelioma.
AB  - The expression of cyclooxygenase 2 (COX-2) protein is increased in many tumours
      and may be associated with a more aggressive phenotype. We aimed to assess COX-2
      expression in a large series of archival mesothelioma specimens. Archival tissue
      was obtained from 86 malignant pleural mesothelioma samples (histological
      subtype: 42 epithelial, 28 biphasic and 16 sarcomatoid). Overexpression of COX-2
      was detected by immunohistochemical analysis. Positive staining was located in
      the cytoplasm of malignant tumour cells. Overall 51/86 (59%) tumour sections
      demonstrated COX-2 overexpression. The frequency varied with histological subtype
      with 31/42 (73%) of epithelial sections, 14/28 (50%) of biphasic sections and
      6/16 (37%) of sarcomatoid sections recorded as positive. Kaplan Meier survival
      analysis indicated that overexpression of COX-2 was significantly related to
      improved prognosis (P < 0.001) and was an independent prognostic factor in
      multivariant analysis. Overexpression of COX-2 protein may confer a survival
      advantage in mesothelioma patients.

PMID- 15964185
TI  - Translational studies on aromatase, cyclooxygenases, and enzyme inhibitors in
      breast cancer.
AB  - Aromatase expression and enzyme activity in breast cancer patients is greater in
      or near the tumor tissue compared with the normal breast tissue. Regulation of
      aromatase expression in human tissues is quite complex, involving alternative
      promoter sites that provide tissue-specific control. Previous studies in our
      laboratories suggested a strong association between aromatase (CYP19) gene
      expression and the expression of cyclooxygenase (COX) genes. Our hypothesis is
      that higher levels of COX expression result in higher levels of prostaglandin E2
      (PGE2), which in turn increases CYP19 expression through increases in
      intracellular cyclic AMP levels. This biochemical mechanism may explain the
      beneficial effects of non-steroidal anti-inflammatory drugs (NSAIDs) on reducing
      the risks of breast cancer. The effects of NSAIDs (ibuprofen, piroxicam, and
      indomethacin), a COX-1 selective inhibitor (SC-560), and COX-2 selective
      inhibitors (celecoxib, niflumic acid, nimesulide, NS-398, and SC-58125) on
      aromatase activity and CYP19 expression were investigated in breast cancer cell
      culture systems. Dose-dependent decreases in aromatase activity were observed
      following treatment with an NSAID or COX inhibitor, with the most effective
      agents being COX selective inhibitors. Real time PCR analysis of aromatase gene
      expression showed a significant decrease in mRNA levels in treated cells when
      compared to vehicle control. These results suggest that the effect of COX
      inhibitors on aromatase occurs at the transcriptional level. To further probe
      these interactions, short interfering RNAs (siRNA) were designed against either
      human CYP19 mRNA or human COX-2 mRNA. Treatment of breast cancer cells with
      aromatase siRNAs suppressed CYP19 mRNA and aromatase enzyme activity. Finally,
      treatment with COX-2 siRNAs downregulated the expression of COX-2 mRNA;
      furthermore, the siCOX-2-mediated suppression of COX-2 also resulted in
      suppression of aromatase mRNA. In summary, pharmacological regulation of
      aromatase and cyclooxygenases can act locally in an autocrine fashion to decrease
      the biosynthesis of estrogen and may provide additional therapy options for
      patients with hormone-dependent breast cancer.

PMID- 15964186
TI  - Purification and properties of a heat-stable exoinulinase isoform from
      Aspergillus fumigatus.
AB  - An inducible extracellular exoinulinase (isoform II) was purified from the
      extracellular extract of Aspergillus fumigatus by ammonium sulphate
      precipitation, followed by successive chromatographies on DEAE-Sephacel, Octyl
      Sepharose (HIC), Sephacryl S-200, affinity chromatography on ConA-CL Agarose and
      Sephacryl S-100 columns. The enzyme was purified 75-folds with 3.2% activity
      yield from the starting culture broth. The purified isoform II was a monomeric 62
      kDa protein with a pI value of 4.5. The enzyme showed maximum activity at pH 6.0
      and was stable over a pH range of 4.0-7.0, whereas the optimum temperature for
      enzyme activity was 60 degrees C. The inulinase isoform II showed exo
      inulinolytic activity and retained 72% and 44% residual activity after 12 h at 60
      degrees C and 70 degrees C, respectively. The inulin hydrolysis activity was
      completely abolished with 5 mM Hg2+ and Fe2+, whereas K+ and Cu2+ enhanced the
      inulinase activity. As compared to sucrose, stachyose and raffinose the purified
      enzyme had a lower Km (1.25 mM) and higher catalytic center activity (Kcat = 3.47
      x 10(4) min(-1)) for inulin. As compared to exoinulinase isoform I of A.
      fumigatus, purified earlier, the isoform II is more thermostable and is a
      potential candidate for commercial production of fructose from inulin.

PMID- 15964187
TI  - Use of microbial activity parameters for determination of a biosolid stability
      index.
AB  - Variations in microbial activity during the aerobic digestion of sludge generated
      at wastewater treatment plants were studied. Results obtained by the measurement
      of enzymatic activity and microbiological parameters were compared with those
      determined by traditional methods (COD, suspended solids, etc.). Their variation
      with digestion time was monitored for batch digestion over a period of 135 days.
      The relationship between these measurements and control parameters of the sludge
      was also investigated. It was found that the traditional physicochemical and
      microbiological parameters present a series of problems which detract from their
      usefulness. The enzymatic parameters dehydrogenase activity (primary metabolism)
      and esterase activity (secondary metabolism) are better able to characterise the
      process, and the ratio of these two variables may be used to estimate the degree
      of endogenesis and, consequently, the degree of stability of the aerobic sludge
      digestion. In addition, these techniques are swift and simple to employ.

PMID- 15964188
TI  - Odour and ammonia emissions from intensive poultry units in Ireland.
AB  - Odour and ammonia emissions were measured from three broiler, two layer and two
      turkey houses in Ireland. The broiler units gave a large range of odour and
      ammonia emission rates depending on the age of the birds and the season. A
      considerable variation between the odour and ammonia emission rates was evident
      for the two layer units which may have been due to the different manure handling
      systems utilised in the houses. There was relatively little difference in the
      odour and ammonia emissions from the two turkey houses. As a precautionary
      principle, odour emission rates utilised in atmospheric dispersion models should
      use the maximum values for broilers and turkeys (1.22 and 10.5 ou(E) s(-1) bird(
      1) respectively) and the mean value for the layers depending on the manure
      handling system used (0.47 or 1.35 ou(E) s(-1) bird(-1)).

PMID- 15964189
TI  - Phosphorus retention in filter materials for wastewater treatment and its
      subsequent suitability for plant production.
AB  - Constructed sand filter beds are advantageous for the treatment of wastewater in
      areas with a low population density. Phosphorus-sorbing materials with additional
      beneficial characteristics may be used instead of sand. This study aimed at
      determining and comparing phosphorus (P) retention capacities of amorphous and
      crystalline blast furnace slags, limestone, opoka, Polonite and sand, for
      filtering domestic wastewater through columns over a period of 67 weeks. The P
      enriched filter materials were subsequently tested for their fertilizer
      effectiveness in a pot experiment where barley was cultivated. Polonite, i.e.
      calcinated bedrock opoka, was most effective in removing P. This occurred at a
      relatively high hydraulic conductivity that reduced the risk of clogging. Barley
      grown in two types of slag, with a grain size of 0.25-4 mm, was most effective in
      dry matter production followed by Polonite. Fine-grained slags and Polonite were
      suggested as most suited of the investigated materials to recycle P back to
      agriculture.

PMID- 15964190
TI  - Biosorption of aqueous chromium(VI) by Tamarindus indica seeds.
AB  - The effectiveness of low cost agro-based materials namely, Tamarindus indica seed
      (TS), crushed coconut shell (CS), almond shell (AS), ground nut shell (GS) and
      walnut shell (WS) were evaluated for Cr(VI) removal. Batch test indicated that
      hexavalent chromium sorption capacity (q(e)) followed the sequence q(e)(TS) >
      q(e)(WS) > q(e)(AS) > q(e)(GS) > q(e)(CS). Due to high sorptive capacity,
      tamarind seed was selected for detailed sorption studies. Sorption kinetic data
      followed first order reversible kinetic fit model for all the sorbents. The
      equilibrium conditions were achieved within 150 min under the mixing conditions
      employed. Sorption equilibria exhibited better fit to Freundlich isotherms
      (R>0.92) than Langmuir isotherm (R approximately = 0.87). Hexavalent chromium
      sorption by TS decreased with increase in pH, and slightly reduced with increase
      in ionic strength. Cr(VI) removal by TS seems to be mainly by chemisorption.
      Desorption of Cr(VI) from Cr(VI) laden TS was quite less by distilled water and
      HCl. Whereas with NaOH, maximum desorption achieved was about 15.3%. When TS was
      used in downflow column mode, Cr(VI) removal was quite good but head loss
      increased as the run progressed and was stopped after 200 h.

PMID- 15964191
TI  - Isolation and characterization of collagen from brown backed toadfish
      (Lagocephalus gloveri) skin.
AB  - Collagen was isolated and characterized from the skin of brown backed toadfish
      (Lagocephalus gloveri), processing wastes. The total collagen yield extracted was
      54.3% on the basis of lyophilized dry weight compared to other vertebrates.
      According to the electrophoretic pattern, the skin collagen of the fish consisted
      of heterotrimer alpha1alpha2alpha3. Moreover, the denaturation temperature was 28
      degrees C, which was about 9 degrees C lower than that of collagen from porcine
      skin. Therefore, there is a possibility to use brown backed toadfish skin
      collagen as an alternative source of collagen for industrial purposes and
      subsequently it may maximize the economical value of the fish.

PMID- 15964192
TI  - Odour and ammonia emissions from intensive pig units in Ireland.
AB  - Odour and ammonia emissions were measured at four intensive pig units in Ireland.
      Odour samples were collected on-site and analysed for odour concentration using
      an olfactometer. Ammonia concentrations in the exhaust ventilation air were
      measured using a portable sensor. The geomean odour emission rates over the four
      pig units were 17.2, 44.4, 4.3, 9.9 and 16.8 ou(E) s(-1) animal(-1) for dry sows,
      farrowing sows, first stage weaners, second stage weaners and finishers,
      respectively. The mean ammonia emission rates, measured at two of the units, were
      12.1, 17.1, 1.4, 2.9 and 10.0 g d(-1) animal(-1) for dry sows, farrowing sows,
      first stage weaners, second stage weaners and finishers, respectively. In
      general, the odour and ammonia emission rates were comparable to those reported
      in literature, although some odour emission rate figures were noticeably lower
      for finishing pigs in this study. The variability in the data highlights the need
      for individual site assessment.

PMID- 15964193
TI  - Parents in accident and emergency: roles and concerns.
AB  - Attending Accident and Emergency (A&E) with a child who has sustained a minor
      injury is a common experience for parents. Little research has focused on
      parents' behaviour in these circumstances, but children in previous studies have
      identified parents as their primary source of support. This article reports
      findings from a qualitative study that reveals the responsibilities that parents
      adopt and the concerns they express. Data were collected through observation of
      the A&E experience of thirty-four children and the parents who accompanied them.
      Ten parents were interviewed at home a few days after the visit to A&E. Analysis
      revealed that parents adopted a number of roles: support, advocate, communicator,
      guide/enforcer and entertainer. Sources of concern included the child's injuries,
      but responsibilities such as work and the welfare of other siblings became more
      pressing once parents realised that the child's injuries were not serious. In
      addition parents' behaviour and comments indicated that they were anxious that
      practitioners should see them as responsible and caring parents. Anxieties could
      impair parents' ability to adopt the roles described suggesting that
      practitioners seeking to reduce the psychological impact of A&E encounters on the
      child must also recognise and manage parental concerns.

PMID- 15964194
TI  - No change in my asthma!

PMID- 15964195
TI  - Thiourea-based non-nucleoside inhibitors of HIV reverse transcriptase as
      bifunctional organocatalysts in the asymmetric Strecker synthesis.
AB  - The potential of novel and known pyridyl thiourea derivatives (non-nucleoside
      inhibitors (NNI) of HIV reverse transcriptase) as bifunctional organic catalysts
      in the asymmetric Strecker synthesis was investigated. It was shown that
      incorporation of the imidazolyl moiety in place of a pyridyl group results in a
      new thiourea derivative that displays a much higher catalytic activity.

PMID- 15964196
TI  - Determination of dosimetric characteristics of OptiSeed(TM) a plastic
      brachytherapy (103)Pd source.
AB  - A new (103)Pd plastic brachytherapy source, OptiSeed(TM) Model 1032P, is being
      introduced by International Brachytherapy sa (IBt). Measurements of the dose
      distributions about the source were performed using LiF thermoluminescent
      dosimeters (TLD-100) in Virtual Water(TM). MCNP5 calculations were performed to
      determine the dose distributions in Virtual Water(TM) and liquid water. The
      source dose rate constant, radial dose function, anisotropy function and
      anisotropy factor have been determined following the updated AAPM TG-43
      recommendations. The measured dose rate constant in the Virtual Water(TM) phantom
      was determined to be 0.727+/-6.9% cGyh(-1)U(-1), and the computed value is
      0.716+/-2.1% cGyh(-1)U(-1). The Monte-Carlo simulation yielded a dose rate
      constant of 0.665+/-2.1% cGyh(-1)U(-1) in water. The measured dose rate constant
      in water is 0.675+/-7.5% cGyh(-1)U(-1). It is determined by multiplying the dose
      rate constant measured in the Virtual Water(TM) phantom with the ratio of the
      value calculated in water to that in Virtual Water(TM). The average of the
      measured and calculated dose rate constant is 0.670+/-5.5% cGyh(-1)U(-1). The
      radial dose functions of the new source were measured for distances ranging from
      1 to 7 cm in a Virtual Water(TM) phantom. The anisotropy functions in Virtual
      Water(TM) phantom were measured for distances of 2, 3, 5, and 7 cm. The Monte
      Carlo computed radial dose functions, anisotropy functions, and anisotropy
      factors in both Virtual Water(TM) phantom and water are reported.

PMID- 15964197
TI  - The CHRNB2 mutation I312M is associated with epilepsy and distinct memory
      deficits.
AB  - Mutations in nAChRs are found in a rare form of nocturnal frontal lobe epilepsy
      (ADNFLE). Previously, some nAChR mutations have been described that are
      associated with additional neurological features such as psychiatric disorders or
      cognitive defects. Here, we report a new CHRNB2 mutation located in transmembrane
      region 3 (M3), outside the known ADNFLE mutation cluster. The CHRNB2 mutation
      I312M, which occurred de novo in twins, markedly increases the receptor's
      sensitivity to acetylcholine. Phenotypically, the mutation is associated not only
      with typical ADNFLE, but also with distinct deficits in memory. The cognitive
      problems are most obvious in tasks requiring the organization and storage of
      verbal information.

PMID- 15964199
TI  - Effect of pro-inflammatory cytokines on spontaneous apoptosis in leukocyte sub
      sets within a whole blood culture.
AB  - Pro-inflammatory cytokines are known to affect apoptosis in human peripheral
      blood cells. Neutrophils, which are an essential component of the immune response
      and usually undergo apoptosis rapidly, are greatly affected by these cytokines.
      In this study, the effect of varying concentrations of TNF-alpha, IL-1beta and IL
      6 on the apoptotic response of leukocytes and their sub-sets in cultured whole
      blood were studied over a 48 h culture period. At clinically relevant
      concentrations, it was found that these pro-inflammatory cytokines reduced the
      amount of spontaneous apoptosis in neutrophils in culture, but had little effect
      on the lymphocyte population. Distinct differences in the sensitivity of
      neutrophils to cytokine-mediated protection against spontaneous apoptosis were
      apparent when compared to previous studies conducted using purified or enriched
      neutrophil cultures. IL-1beta, at a dose of 0.01 pg/mL, was observed to
      significantly inhibit spontaneous neutrophil apoptosis by approximately 90% and
      65% at 24 and 48 h of culturing, respectively. This concentration used in whole
      blood is dramatically lower than that required to elicit similar protection in
      neutrophil-enriched cell cultures. Higher concentrations of TNF-alpha (1.0 pg/mL)
      and IL-6 (125 pg/mL) were also found to significantly inhibit neutrophil
      apoptosis, at levels much lower than previously published using neutrophil
      enriched cultures. Furthermore, each cytokine displayed a unique signature with
      respect to the optimal applied doses required to elicit maximal protection
      against spontaneous neutrophil apoptosis. These results demonstrate the dramatic
      differences in cellular responses that exist between neutrophil-enriched cultures
      and whole blood culture systems, where multiple blood cell types provide a much
      more complex environment.

PMID- 15964200
TI  - Urinary pharmacokinetics of betalains following consumption of red beet juice in
      healthy humans.
AB  - The aim of the present pilot study was to characterise the renal elimination of
      betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking
      female volunteers were given a single oral dose of either 500 mL of a commercial
      RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a
      sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal
      excretion of betalains was determined spectrophotometrically and quantified as
      betanin-equivalents. In addition, the identity of individual compounds was
      confirmed by HPLC coupled with diode-array detection and positive ion
      electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact
      betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg
      corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates
      were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to
      91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the
      corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively.
      Using the lambdaz estimates obtained the expected total betalain amount excreted
      in urine was 1228+/-291 microg. Based on the results obtained it is assumed that
      either the bioavailability of the betalains is low or that renal clearance is a
      minor route of systemic elimination for these compounds. The urinary excretion
      rates of unmetabolised betalains were fast and appeared to be monoexponential
      suggesting a one-compartment model. In order to get a more complete picture of
      the pharmacokinetics and health-promoting properties of red beet betalains,
      quantitative data on betalain bioavailability should include measurements of
      unchanged compounds and their corresponding metabolites in plasma, urine and
      bile.

PMID- 15964198
TI  - Transcriptional repression and cell death induced by nuclear aggregates of non
      polyglutamine protein.
AB  - Nuclear aggregates of polyglutamine (polyQ)-expanded proteins are associated with
      a number of neurodegenerative diseases including Huntington's disease (HD) and
      spinocerebellar ataxias (SCAs). The nuclear deposition of polyQ proteins
      correlates with rearrangements of nuclear matrix, transcriptional dysregulation,
      and cell death. To explore the requirement for polyQ tracks in educing such
      cellular responses, we examined whether a non-polyQ protein can deposit as
      nuclear aggregates and elicit similar responses. We report that a protein chimera
      (GFP170*) composed of the green fluorescent protein (GFP) fused to an internal
      fragment of the Golgi Complex Protein (GCP-170) forms nuclear aggregates
      analogous to those formed by polyQ proteins. Like the polyQ nuclear aggregates,
      GFP170* inclusions recruit molecular chaperones and proteasomal components, alter
      nuclear structures containing the promyelocytic leukemia protein (PML), recruit
      transcriptional factors such as CREB-binding protein (CBP) and p53, repress p53
      transcriptional activity, and induce cell death. Our results indicate that
      nuclear aggregation and transcriptional effects are not unique to polyQ
      containing proteins and may represent a general response to misfolded proteins in
      the nucleus.

PMID- 15964201
TI  - Homeostasis and the age-associated defect of CD4 T cells.
AB  - Survival and homeostatic division of naive CD4 T cells is regulated by the
      cellular and non-cellular milieu and together these processes ensure that a
      population of naive CD4 T cells persists into old age. However, the naive CD4 T
      cells from aged animals show reduced IL-2 production, proliferation, helper
      function and effector generation and memory function. We explore here whether the
      age-related defects in naive CD4 T cells are due to the aged environment from
      which they come or to intrinsic defects that are caused by homeostasis and their
      long lifespan.

PMID- 15964202
TI  - Characterization of recombinant Francisella tularensis acid phosphatase A.
AB  - Francisella tularensis is the etiologic agent of the potentially fatal human
      disease tularemia and is capable of survival and multiplication within
      professional phagocytes of the host. While the mechanisms that allow
      intracellular survival of the bacterium are only now beginning to be elucidated
      at the molecular level, previous work demonstrated that F. tularensis produces
      copious levels of an acid phosphatase which in crude and purified form affected
      the dose-dependent abrogation of the respiratory burst of stimulated neutrophils.
      The work presented here was undertaken to provide a source of recombinant F.
      tularensis acid phosphatase for detailed biochemical, biological, and structural
      studies. Results from this work are consistent with the ability to generate
      milligram amounts of recombinant enzyme whose attributes are demonstrably
      equivalent to those of the native enzyme. Such properties include molecular mass,
      broad substrate specificity, sensitivity and resistance to various inhibitors, pH
      optimum, and reactivity with rabbit polyclonal antibody to the native enzyme.

PMID- 15964204
TI  - Antifibrinolytic agents in traumatic hemorrhage.

PMID- 15964203
TI  - Congestive heart failure incidence and prognosis: case identification using
      central adjudication versus hospital discharge diagnoses.
AB  - PURPOSE: We compared hospitalized congestive heart failure (CHF) incidence and
      prognosis estimates using hospital discharge diagnoses or central adjudication.
      METHODS: We used the Cardiovascular Health Study (CHS), a population-based cohort
      study of 5888 elderly adults. A physician committee adjudicated potential CHF
      events, confirmed by signs, symptoms, clinical tests, and/or medical therapy. A
      CHF discharge diagnosis included any of these ICD-9 codes in any position: 428,
      425, 398.91, 402.01, 402.11, 402.91, and 997.1. We constructed an inception
      cohort of 1209 hospitalized, nonfatal, incident CHF cases, identified by
      discharge diagnosis, adjudication, or both. RESULTS: Incidence rates for
      hospitalized CHF were 24.6 per 1000 person-years using discharge diagnoses and
      17.1 per 1000 person-years using central adjudication. Compared to the group
      identified as having CHF by both methods, the group with only a discharge
      diagnosis (hazard ratio=0.77, 95% confidence interval=0.65-0.91) and the group
      with central adjudication only (hazard ratio=0.72, 95% confidence interval=0.55
      0.94) had lower mortality rates. CONCLUSIONS: In the elderly, studies using only
      discharge diagnoses, as compared to central adjudication, may estimate higher
      rates of incident hospitalized CHF. Mortality following CHF onset may be similar
      for these methods and higher if both methods are used together.

PMID- 15964205
TI  - The cementum-dentin junction also contains glycosaminoglycans and collagen
      fibrils.
AB  - The presence of glycosaminoglycans (GAGs) and their contribution to mechanical
      properties of the cementum-dentin junction (CDJ) were investigated using
      nanometer scale characterization techniques. Five to two millimeter thick
      transverse sections from the apical ends of human molars were ultrasectioned at
      room temperature under wet conditions using a diamond knife and an
      ultramicrotome. The structure of the CDJ under dry and wet conditions before and
      after digestion of GAGs and collagen fibrils was studied using an atomic force
      microscope (AFM). The mechanical properties of the untreated and enzyme treated
      CDJ under wet conditions were studied using an AFM-based nanoindenter. GAG
      digestion was performed for 1, 3, and 5 h at 37 degrees C using chondroitinase
      ABC. Collagen fibril digestion was performed for 24 and 48 h at 37 degrees C
      using collagenase. As reported previously, AFM scans of dry untreated CDJ
      (control) revealed a valley, which transformed into a peak under wet conditions.
      The height differences relative to cementum and dentin of untreated and treated
      CDJ were determined by measuring the CDJ profile under dry and wet conditions.
      The depth of the valley of GAG and collagen-digested CDJ was greater than that of
      undigested CDJ under dry conditions. The height of the peak of GAG-digested CDJ
      was significantly higher than that of the undigested CDJ under wet conditions.
      The collagen-digested CDJ under wet conditions is assumed to form a valley
      because of the removal of collagen fibrils from the CDJ. However, the depth of
      the valley was lower compared to the depth under dry conditions. Wet AFM-based
      nanoindentation showed that the elastic modulus and hardness of control (3.3+/
      1.2 and 0.08+/-0.03 GPa) were significantly higher (ANOVA & SNK, P < 0.05) than
      chondroitinase-ABC treated CDJ (0.9+/-0.4 and 0.02+/-0.004 GPa) and collagenase
      treated CDJ (1.5+/-0.6 and 0.04+/-0.01 GPa). No significant difference in
      mechanical properties between chondroitinase-ABC and collagenase treated CDJ was
      observed. Based on the results it was concluded that the 10-50 microm wide CDJ is
      a composite that includes, chondroitin-4-sulfate, chondroitin-6-sulfate, and
      possibly dermatan sulfate, and collagen fibrils. The association of GAGs with the
      collagen fibrils provides the observed controlled hydration and partially
      contributes toward the stiffness of the CDJ under wet conditions.

PMID- 15964206
TI  - Native polysomes of Saccharomyces cerevisiae in liquid solution observed by
      atomic force microscopy.
AB  - The native polysomes of Saccharomyces cerevisiae were visualized in liquid
      solution by atomic force microscopy without external contrasting, such as
      shadowing and negative staining. This study showed native polysomes as lined
      particle with a height of ca. 27 nm, which is agreement with the height of 80S
      ribosomes in previous study. We found a small subparticle, located in a ring
      shape or at the end of a linear structure, and visualized mRNA chains between
      adjacent ribosomes. Although the structures of polysomes have been studied for
      decades, it has remained difficult to visualize the native three-dimensional
      form. By the observation in liquid solution, we temporarily stopped the
      translation using an antibiotic to presenting the native three-dimensional
      structure and function of the polysomes. Our results provide not only new
      findings on native eukaryotic polysomes, but also great potential to visualize
      the influence of various environmental conditions on polysomes.

PMID- 15964207
TI  - Neuromagnetic responses reflect the temporal pitch change of regular interval
      sounds.
AB  - The pitch onset response (POR) evoked by the transition between two regular
      interval sounds (RIS) with different pitch was studied by recording the
      neuromagnetic responses with a 122-channel whole head magnetoencephalograph
      (MEG). The parameters of RIS were varied giving rise to characteristic changes in
      the latency of the first prominent deflection occurring about 100 to 140 ms after
      the transition. These latency differences of the neurophysiological signal
      correlated strongly with the psychoacoustic findings obtained from the same
      individuals. Some of the observed changes cannot be explained by obvious physical
      differences as changes in the spectrum, but only by temporal processing
      mechanisms as the auditory image model (Patterson, R.D., Allerhand, M., Giguere,
      C., 1995. Time-domain modelling of peripheral auditory processing: a modular
      architecture and a software platform. J. Acoust. Soc. Am. 98, 1890-1894). The
      location of the POR evoked by the transition was found to be in lateral Heschl's
      Gyrus, which gives further evidence that this is the center of processing pitch
      changes in the auditory cortex.

PMID- 15964208
TI  - Separating semantic conflict and response conflict in the Stroop task: a
      functional MRI study.
AB  - Attentive behavior requires the ability to perform in the face of distraction.
      Distracting information can cause conflict at any level along the information
      processing stream. However, it is not yet known whether the brain has distinct
      subsystems dedicated to detecting and resolving these different forms of
      distraction. Although previous studies have localized brain activity during
      semantic and response conflict, no prior study has specifically determined
      whether these activations occur in distinct or overlapping regions. We used a
      modified version of the Stroop color-word task, by which we were able to separate
      semantic from response conflict. Behavioral data indicate that these two kinds of
      conflict both contribute to the overall Stroop interference effect, while fMRI
      data indicate that they elicit non-overlapping activation in anterior cingulate,
      prefrontal, and parietal brain regions. These results suggest that the brain has
      distinct but parallel attentional mechanisms for resolving these different forms
      of cognitive interference.

PMID- 15964209
TI  - Content-specific activation during associative long-term memory retrieval.
AB  - We tested whether visual stimulus material that is assumed to be processed in
      different cortical networks during perception (i.e., faces and spatial positions)
      is also topographically dissociable during long-term memory recall. With an
      extensive overlearning procedure, 12 participants learned paired associates of
      words and faces and words and spatial positions. Each word was combined with
      either one or two positions or one or two faces. fMRI was recorded several days
      later during a cued recall test, in which two words were presented and the
      participants had to decide whether these were linked to each other via a common
      mediator, i.e., a face or a position. This paradigm enforces retrieval from long
      term memory without confounding recall with perceptual processes. A network of
      cortical areas was found to be differently activated during recall of positions
      and faces, including regions along the dorsal and ventral visual pathways, such
      as the parietal and precentral cortex for positions and the left prefrontal,
      temporal (including fusiform gyrus) and posterior cingulate cortex for faces. In
      a subset of these areas, the BOLD response was found to increase monotonically
      with the number of the to-be-re-activated associations. These results show that
      material-specific cortical networks are systematically activated during long-term
      memory retrieval that overlap with areas also activated by positions and faces
      during perceptual and working memory tasks.

PMID- 15964210
TI  - Thinking about intentions.
AB  - In this fMRI study, we investigated the convergence of underlying neural networks
      in thinking about a scenario involving one's own intentional action and its
      consequences and setting up and holding in mind an intention to act. A factorial
      design was employed comprising two factors: i. Causality (intentional or physical
      events) and ii. Prospective Memory (present or absent). In each condition,
      subjects answered questions about various hypothetical scenarios, which related
      either to the link between the subject's own intentions and consequential actions
      (Intentional Causality) or to the link between a natural, physical event and its
      consequences (Physical Causality). A prospective memory task was embedded in half
      the blocks. In this task, subjects were required to keep in mind an intention (to
      press a key on seeing a red stimulus background) whilst carrying out the ongoing
      Causality task. Answering questions about intentional causality versus physical
      causality activated a network of regions that have traditionally been associated
      with Theory of Mind, including the medial prefrontal cortex (mPFC), the superior
      temporal sulcus and the temporal poles bilaterally. In addition, the precuneus
      bordering with posterior cingulate cortex, an area involved in self-awareness and
      self-related processing, was activated more when thinking about intentional
      causality. In the prospective memory task, activations were found in the right
      parietal cortex, frontopolar cortex (BA 10) and precuneus. Different subregions
      within the precuneus/posterior cingulate cortex were activated in both main
      effects of intentional causality and prospective memory. Therefore, the
      precuneus/posterior cingulate cortex subserves separately thinking about one's
      own intentions and consequent actions and bearing in mind an intention to make an
      action. Previous studies have shown that prospective memory, requiring the
      formation of an intention and the execution of a corresponding action, is
      associated with decreased activation in the dorsal mPFC, close to the region
      activated in Theory of Mind tasks. Here, we found that holding in mind an
      intention to act and at the same time thinking about an intentional action led to
      reduced activity in a dorsal section of the mPFC. This was a different region
      from a more anterior, inferior dorsal mPFC region that responded to intentional
      causality. This suggests that different regions of mPFC play different roles in
      thinking about intentions.

PMID- 15964211
TI  - Hypnosis decouples cognitive control from conflict monitoring processes of the
      frontal lobe.
AB  - Hypnosis can profoundly alter sensory awareness and cognitive processing. While
      the cognitive and behavioral phenomena associated with hypnosis have long been
      thought to relate to attentional processes, the neural mechanisms underlying
      susceptibility to hypnotic induction and the hypnotic condition are poorly
      understood. Here, we tested the proposal that highly hypnotizable individuals are
      particularly adept at focusing attention at baseline, but that their attentional
      control is compromised following hypnosis due to a decoupling between conflict
      monitoring and cognitive control processes of the frontal lobe. Employing event
      related fMRI and EEG coherence measures, we compared conflict-related neural
      activity in the anterior cingulate cortex (ACC) and control-related activity in
      the lateral frontal cortex (LFC) during Stroop task performance between
      participants of low and high hypnotic susceptibility, at baseline and after
      hypnotic induction. The fMRI data revealed that conflict-related ACC activity
      interacted with hypnosis and hypnotic susceptibility, in that highly susceptible
      participants displayed increased conflict-related neural activity in the hypnosis
      condition compared to baseline, as well as with respect to subjects with low
      susceptibility. Cognitive-control-related LFC activity, on the other hand, did
      not differ between groups and conditions. These data were complemented by a
      decrease in functional connectivity (EEG gamma band coherence) between frontal
      midline and left lateral scalp sites in highly susceptible subjects after
      hypnosis. These results suggest that individual differences in hypnotic
      susceptibility are linked with the efficiency of the frontal attention system,
      and that the hypnotized condition is characterized by a functional dissociation
      of conflict monitoring and cognitive control processes.

PMID- 15964212
TI  - Multiple invasions of the Ryukyu Archipelago by Oriental frogs of the subgenus
      Odorrana with phylogenetic reassessment of the related subgenera of the genus
      Rana.
AB  - The genus Rana, notably diversified in Oriental regions from China to Southeast
      Asia, includes a group of cascade frogs assigned to subgenera Odorrana and
      Eburana. Among them, R. ishikawae and the R. narina complex represent the
      northernmost members occurring from Taiwan to the Ryukyu Archipelago of Japan.
      Relationships of these frogs with the continental members, as well as the history
      of their invasions to islands, have been unclear. The taxonomic status of
      Odorrana and related genera varies among authors and no phylogenetic reassessment
      has been done. Using partial sequences of mitochondrial 12S and 16S rRNA genes,
      we estimated phylogenetic relationships among 17 species of the section Hylarana
      including Odorrana and Eburana, and related species from the Ryukyus, Taiwan,
      China, Thailand, Malaysia, and Indonesia. We estimate that (1) Odorrana is
      monophyletic and encompasses species of Eburana and R. hosii, which is now placed
      in Chalcorana, (2) the ancestor of R. ishikawae separated from other Rana in the
      middle to late Miocene prior to its entry to the Ryukyu Archipelago, (3) the
      ancestor of the R. narina complex later diversified in continental Asia, and
      invaded the Ryukyu Archipelago through Taiwan, (4) the R. narina complex attained
      its current distribution within the Ryukyus through niche segregations, and (5)
      vicariance of R. hosii between Malay Peninsula and Borneo occurred much later
      than the divergence events in the R. narina complex. Current subgeneric
      classification of Rana, at least of Southeast Asian members, requires full
      reassessment in the light of phylogenetic relationships.

PMID- 15964213
TI  - Phylogenetic relationships of the lamprologine cichlid genus Lepidiolamprologus
      (Teleostei: Perciformes) based on mitochondrial and nuclear sequences, suggesting
      introgressive hybridization.
AB  - Using sequences of the mitochondrial NADH dehydrogenase subunit 2 gene (ND2,
      1047bp) and a segment of the non-coding mitochondrial control region, as well as
      nuclear sequences including two introns from the S7 ribosomal protein and the
      loci TmoM25, TmoM27, and UME002, we explore the phylogenetic relationships of
      Lepidiolamprologus, one of seven lamprologine cichlid genera in Lake Tanganyika,
      East Africa. Analyses consisted of direct optimization using POY, including a
      parsimony sensitivity analysis, and maximum likelihood and Bayesian inference for
      comparison. With respect to Lepidiolamprologus, the results based on the
      mitochondrial dataset were robust to parameter variation in POY.
      Lepidiolamprologus cunningtoni was resolved in a large clade sister to ossified
      group lamprologines, among which the remaining Lepidiolamprologus were nested. In
      addition to L. attenuatus, L. elongatus, L. kendalli, and L. profundicola,
      Neolamprologus meeli, N. hecqui, N. boulengeri, N. variostigma, and two
      undescribed species were resolved in a two-pore Lepidiolamprologus clade sister
      to Lamprologus callipterus and two species of Altolamprologus. Lepidiolamprologus
      nkambae, in marked conflict with morphological and nuclear DNA evidence, nested
      outside of the two-pore Lepidiolamprologus clade, suggesting that the mtDNA
      signal has been convoluted by introgressive hybridization.

PMID- 15964214
TI  - Molecular phylogeography of Dolichopoda cave crickets (Orthoptera,
      Rhaphidophoridae): a scenario suggested by mitochondrial DNA.
AB  - This study focuses on the phylogenetic relationships among a number of West
      Mediterranean cave crickets species belonging to Dolichopoda; primarily a
      Mediterranean genus, distributed from eastern Pyrenees to Caucasus. In this
      paper, 11 Dolichopoda species from the French Pyrenees (D. linderi), the island
      of Corsica (D. bormansi and D. cyrnensis), and northern, central, and southern
      Italy (D. ligustica, D. schiavazzii, D. aegilion, D. baccettii, D. laetitiae, D.
      geniculata, D. capreensis, and D. palpata) were studied. Two more species, one
      from the Caucasus, D. euxina, and one from Greece, D. remyi, were also included
      in the analyses, together with more distant species within the same family to be
      used as outgroups. Fifteen hundred base pairs of mitochondrial DNA, corresponding
      to the small subunit of the ribosomal RNA (16S rRNA) and to the subunit I of the
      cytochrome oxidase I (COI), were sequenced in order to clarify the phylogenetic
      relationships and biogeography of this group of Mediterranean cave crickets. The
      molecular data are congruent with a phylogeographic pattern; with the
      geographically close species also the most related ones. Based on mtDNA
      divergence, the present-day distribution of genetic diversity seems to have been
      impacted by climatic events due to glacial and interglacial cycles that have
      characterized the Pleistocene era.

PMID- 15964215
TI  - A phylogeny of the Caniformia (order Carnivora) based on 12 complete protein
      coding mitochondrial genes.
AB  - Evolutionary relationships of the order Carnivora have been extensively studied.
      However, phylogenetic studies based on different types of data, species samples,
      and methods of analysis provide contradictory results. Consequently, phylogenetic
      relationships of Carnivora remain contentious. Here, the sequence of 12
      mitochondrial genes (10,842 nucleotides) from a total of 38 carnivore species was
      used to investigate the phylogeny of the caniform (dog-like) carnivores. An
      analysis using maximum parsimony, maximum likelihood, and Bayesian approaches
      provided a unique and well-supported solution to most contentious relationships
      within Caniformia. The clade Arctoidea was shown to consist of three major
      monophyletic groups: Pinnipedia, Ursidae, and Musteloidea. Within Pinnipedia, the
      families Otariidae and Odobenidae formed a clade, sister to Phocidae. Within
      Musteloidea, there was a sister relationship between true mustelids (i.e.,
      excluding the skunks) and procyonids, and between ailurids and mephitids
      (skunks). Despite a high level of confidence obtained at most nodes, uncertainty
      remained about the relative position of the three major arctoid clades.

PMID- 15964216
TI  - Deep genealogical history without population differentiation: discordance between
      mtDNA and allozyme divergence in the zebra-tailed lizard (Callisaurus
      draconoides).
AB  - The peninsula of Baja California has a complex geological history that has
      strongly affected the regional biota. Genealogical histories of many species have
      revealed congruent patterns, which suggest that the peninsula was temporarily
      submerged at two locations. We sequenced a total of 1953 base pairs (bp) of the
      mitochondrial genome for 42 specimens of the zebra-tailed lizard (Callisaurus
      draconoides). The resulting maternal genealogy supports the former existence of a
      mid-peninsular seaway and a Plio-Quaternary seaway across the Isthmus of La Paz.
      In addition, a genealogical break is revealed in the vicinity of Loreto. This
      genealogical break may have resulted from prolonged submergence of the Loreto
      Basin during Pliocene. The mid-peninsular seaway may have occurred as early as
      late Miocene, at a time significantly earlier than previously hypothesized.
      Comparison with other genealogies and geological evidence suggests that current
      models on the evolution of Baja California's fauna are temporally shallow. The
      deep genealogical patterns of C. draconoides also disagree with the very limited
      population differentiation previously reported for allozyme markers, suggesting
      that maternal history may not be an appropriate approximation for population
      differentiation.

PMID- 15964217
TI  - Molecular phylogenetics and evolution of turtles.
AB  - Turtles are one of Earth's most instantly recognizable life forms, distinguished
      for over 200 million years in the fossil record. Even so, key nodes in the
      phylogeny of turtles remain uncertain. To address this issue, we sequenced >90%
      of the nuclear recombination activase gene 1 (RAG-1) for 24 species representing
      all modern turtle families. RAG-1 exhibited negligible saturation and base
      composition bias, and extensive base composition homogeneity. Most of the
      relationships suggested by prior phylogenetic analyses were also supported by RAG
      1 and, for at least two critical nodes, with a much higher level of support. RAG
      1 also indicates that the enigmatic Platysternidae and Chelydridae, often
      considered sister taxa based on morphological evidence, are not closely related,
      although their precise phylogenetic placement in the turtle tree is still
      unresolved. Although RAG-1 is phylogenetically informative, our research revealed
      fundamental conflicts among analytical methods for estimating phylogenetic
      hypotheses. Maximum parsimony analyses of RAG-1 alone and in combination with two
      mitochondrial genes suggest the earliest phylogenetic splits separating into
      three basal branches, the pig-nosed turtles (Carettochelyidae), the softshell
      turtles (Trionychidae), and a clade comprising all remaining extant turtles.
      Maximum likelihood and Bayesian analyses group Carettochelyidae and Trionychidae
      (=Trionychoidae) in their more traditional location as the sister taxon to all
      other hidden-necked turtles, collectively forming the Cryptodira. Our research
      highlights the utility of molecular data in identifying issues of character
      homology in morphological datasets, while shedding valuable light on the
      biodiversity of a globally imperiled taxon.

PMID- 15964218
TI  - Phylogeny of calcareous dinoflagellates as inferred from ITS and ribosomal
      sequence data.
AB  - The phylogenetic relationships of calcareous dinoflagellates (i.e.,
      Calciodinellaceae and Thoracosphaera) are investigated. Molecular data from the
      ribosomal 5.8S rRNA and highly conserved motifs of the ITS1 show
      Calciodinellaceae s.l. to be monophyletic when few non-calcareous taxa are
      included. They segregate into three monophyletic assemblages in a molecular
      analysis that considers the 5.8S rRNA and both the Internal Transcribed Spacer
      regions ITS1 and ITS2: a clade comprising species of Ensiculifera and
      Pentapharsodinium (E/P-clade), Scrippsiella s.l. (including fossil-based taxa
      such as Calciodinellum and Calcigonellum), and a heterogeneous group (T/P-clade)
      of calcareous (e.g., Thoracosphaera) and non-calcareous taxa (e.g., the highly
      toxic Pfiesteria). The potential to produce calcareous structures is considered
      as apomorphic within alveolates, and non-calcareous taxa nesting with calcareous
      dinoflagellates may have reduced calcification secondarily. Molecular results do
      not contradict general evolutionary scenarios provided by previous morphological
      (mainly paleontological) investigations.

PMID- 15964219
TI  - Cutting-edge design to improve cell viability in osteochondral grafts.
AB  - INTRODUCTION: Autologous osteochondral grafting is in widespread use for focal
      defects of articular cartilage. There is major concern over the nature of the
      tissue bridging graft elements and graft/recipient cartilage. Chondrocyte
      viability is thought to be an important determinant of the quality of repair. The
      aim of the current study was to compare the zone of death for osteochondral
      grafts harvested with the commercially available Acufex, and an osteotome with a
      specially designed cutting-edge. MATERIALS/METHODS: The circular osteotomes were
      the Acufex 4.5mm MP (Smith & Nephew) and the Lissimore, which has a different
      cutting-tip geometry and sharpness. These implements were used to harvest
      osteochondral plugs from macroscopically non-degenerate human lateral condyle
      explants obtained from the anterior femoral cuts of knee replacement surgery.
      Confocal laser scanning microscopy with vital staining was used to quantify the
      zone of marginal chondrocyte death for the entire perimeter of the plugs.
      RESULTS: The increase in cartilage plug diameter (reference the osteotome minimal
      internal diameter) was significantly greater for the Acufex (Mann-Whitney; n=5;
      P=0.0079), with the diameter (mm) increasing by 0.49+/-0.03 (10.9%), compared
      with 0.16+/-0.02 (3.3%) for the Lissimore. Osteochondral plugs had a
      significantly (Mann-Whitney; n=5; P=0.0079) lower mean margin of cell death with
      the Lissimore osteotome (117.8+/-8.97 microm) than the Acufex MP (315.3+/-5.90
      microm). CONCLUSIONS: Cutting-tip profile is an important factor in determining
      the extent of marginal death in circular osteochondral grafts. We have designed
      and assessed an alternative cutting-tip, which caused significantly less marginal
      death than the commercially available Acufex. We conclude that there is scope for
      improvement of osteochondral harvest techniques.

PMID- 15964220
TI  - Effects of coumarin and 7OH-coumarin on bcl-2 and Bax expression in two human
      lung cancer cell lines in vitro.
AB  - Coumarin and its derivative 7-hydroxycoumarin (7-OHC) have antitumor and
      antimetastatic properties. The purpose of this study was to investigate the
      possible effects of these compounds on expression of the bcl-2 and Bax
      oncoproteins in two human lung cancer cell lines, A427 and Calu-1. The cells were
      cultured in vitro for 24 h in RPMI 1640 with 1.5% (v/v) ethanol, 1.0 mM ethanolic
      coumarin or 1.0 mM ethanolic 7-OHC. Viability was determined in each cell line by
      an MTT assay. Total protein was extracted from cell lysates and the bcl-2 and Bax
      oncoproteins were identified. Western blotting showed a decrease in bcl-2 and an
      increase in Bax in A427 cells cultured with coumarin or 7-OHC. Neither drug
      changed bcl-2 expression in Calu-1 cells compared to solvent controls, and Bax
      expression was only slightly increased by coumarin. We conclude that 7-OHC is a
      more potent inhibitor of cell proliferation than coumarin and has more marked
      effects on oncoprotein expression. Also, the A427 cell line was more sensitive to
      the drugs than Calu-1.

PMID- 15964221
TI  - Pelvic kidney and aorto-iliac aneurysm--a rare association--case report and
      literature review.
AB  - Association of a congenital pelvic kidney with abdominal aortic aneurysm is rare
      and to date only a handful cases have been reported in literature. We report one
      such case, which was successfully treated using the technique of temporary extra
      anatomical perfusion of the kidney.

PMID- 15964222
TI  - The G protein alpha subunit Tga1 of Trichoderma atroviride is involved in
      chitinase formation and differential production of antifungal metabolites.
AB  - Trichoderma mycoparasitism includes recognition, attack, overgrowth and lysis of
      the host fungus accompanied by morphological changes and secretion of hydrolytic
      enzymes and antibiotics. Studying the underlying signal transduction pathways,
      the tga1 gene encoding a Galpha subunit of Trichoderma atroviride P1 was
      analysed. A Deltatga1 mutant showed continuous sporulation and elevated internal
      steady-state cAMP levels. tga1 gene deletion resulted in a complete loss of
      mycoparasitic overgrowth and lysis of Rhizoctonia solani, Botrytis cinerea, and
      Sclerotinia sclerotiorum during direct confrontation, although infection
      structure formation was unaffected. The reduced mycoparasitic abilities were
      reflected by strongly decreased chitinase activities and reduced nag1 and ech42
      gene transcription. Furthermore, production of 6-pentyl-alpha-pyrone and of
      metabolites with sesquiterpene structure was reduced in the Deltatga1 mutant.
      Regardless of these deficiencies, the mutant displayed an enhanced growth
      inhibition of the host fungi by over-producing other low molecular weight
      antifungal metabolites, suggesting opposite roles of Tga1 in regulating the
      biosynthesis of different antifungal substances in T. atroviride.

PMID- 15964223
TI  - The effect of intravesical Bacillus Calmette-Guerin instillations on the
      expression of inducible nitric oxide synthase in humans.
AB  - The activation of the inducible isoform of nitric oxide synthase (NOS) is
      associated with the production of large quantities of nitric oxide in response to
      cytokine stimulation. Bacillus Calmette-Guerin (BCG) mode of action against
      bladder carcinoma remains unclear, although a plethora of local and systemic
      events may follow its intravesical instillation. The present study was designed
      to investigate the expression of inducible NOS in normal and neoplastic
      urothelium and its alteration following tumor resection and subsequent
      intravesical immunotherapy. Bladder carcinoma and autologous normal bladder
      tissue specimens were procured from 36 patients undergoing transurethral
      resection. Tissue specimens were obtained from the same patients at first
      cystoscopy following six weekly intravesical instillations. Inducible NOS protein
      expression was assessed by immunohistochemistry in all tissue specimens.
      Immunostaining of normal urothelium for iNOS before treatment was negative in all
      but four cases. BCG treatment induced iNOS expression in tumor-free bladder
      tissue in 24 cases (66.6%). There were only four early tumor recurrences;
      interestingly, they corresponded to the cases with tumor cells expressing iNOS
      before BCG treatment, while novel tumors were also iNOS immunoreactive. BCG
      upregulated iNOS expression in normal human urothelial cells in vivo suggesting a
      role for nitric oxide in BCG mediated antitumor activity. Inducible NOS was
      detected in certain tumor specimens before and after BCG treatment implying a
      possible involvement in pro-tumor action.

PMID- 15964224
TI  - Quantitative measurements of NO reaction kinetics with a Clark-type electrode.
AB  - Nitric oxide (NO) plays important physiological roles in the body. Knowledge
      regarding the kinetics of NO catabolism is important for understanding the
      biological functions of NO. Clark-type NO electrodes have been frequently
      employed in measuring the kinetics of NO reactions; however, the slow response
      time of these electrodes can cause measurement errors and limit the application
      of the electrode in measurements of fast NO reactions. In this study, a
      simplified diffusion model is given for describing the response process of the NO
      electrode to the change of NO concentration. The least-square method is used in
      fitting the currents calculated from the diffusion equation to the experimental
      curves for determining the diffusion parameters and rate constants. The
      calculated currents are in excellent accordance with the experimental curves for
      different NO reaction kinetics. It has been demonstrated that when using an NO
      electrode with a response time of approximately 6 s to measure fast NO reactions
      with a half-life of approximately 1s, the response currents of the electrode have
      large differences compared to the curve of actual NO concentration in the
      solution; however, the rate constant of NO decay can still be accurately
      determined by computer simulations with the simplified diffusion model.
      Theoretical analysis shows that an NO electrode with a response time of 6 s
      (D/L2=0.06 s-1) and the lowest detection limit of 1 nM NO can be used in
      measuring kinetics of extremely rapid NO reactions with a half-life below 10 ms.

PMID- 15964225
TI  - TGF-beta1 enhances degradation of IFN-gamma-induced iNOS protein via proteasomes
      in RAW 264.7 cells.
AB  - TGF-beta1 is a well-known immunosuppressive cytokine that inhibits inducible
      nitric oxide synthase (iNOS) gene expression in various cells including
      macrophages. In this study, we investigated the suppressive mechanisms of TGF
      beta1 on IFN-gamma-induced iNOS gene expression using the murine macrophage-like
      cell line RAW 264.7. TGF-beta1 decreased iNOS protein amount through enhanced
      degradation, although TGF-beta1 did not affect IFN-gamma-induced iNOS mRNA level
      or stability. In addition, the enhancement of iNOS protein degradation by TGF
      beta1 treatment was almost completely blocked by MG132, a proteasome inhibitor.
      Furthermore, TGF-beta1 enhanced the trypsin-like activity of proteasomes in the
      presence of IFN-gamma, although did not enhance the peptidylglutamyl-peptide
      hydrolyzing and chymotrypsin-like activities of proteasomes. The level of
      ubiquitinated iNOS protein was not significantly altered by IFN-gamma or IFN
      gamma plus TGF-beta1 treatment. Because MG132 inhibited iNOS protein degradation
      and IFN-gamma plus TGF-beta1 treatment increased the trypsin-like activity of
      proteasomes, we hypothesized that TGF-beta1 might enhance iNOS protein
      degradation via the ubiquitin-proteasome pathway in the presence of IFN-gamma. We
      propose that these mechanisms of TGF-beta1 in the posttranslational regulation of
      iNOS gene expression may contribute to suppression of excess nitric oxide during
      inflammatory processes.

PMID- 15964226
TI  - Microbiological survey for Mycoplasma spp. in a contagious agalactia endemic
      area.
AB  - In this work, we report a microbiological survey for Mycoplasma spp. undertaken
      between 2001 and 2002 in 28 goat herds in Gran Canaria, Spain, an area where
      contagious agalactia is endemic. All herds were randomly selected and represented
      approximately 15.5% of the total goat population of the island. A variable number
      of milk, articular and auricular swab samples were collected from each flock and
      cultured in specific mycoplasma culture media. There was a total of 38.5%
      positive flocks from which 37 mycoplasma isolates were obtained. In contrast with
      previous data obtained in Spain, our results showed that the large colony variant
      of M. mycoides subsp. mycoides (Mmm LC) was the most commonly isolated agent
      associated with contagious agalactia. This species was isolated from 90% of the
      positive herds and accounted for 54.1% of all isolations. M. agalactiae was
      isolated from 40% of the positive herds (27% of all isolations) and in six herds
      M. arginini was isolated (18.7% of all isolations). No M. capricolum or M.
      putrefaciens strains were isolated. Mycoplasmas were isolated from 21 milk
      samples, 15 ear canals swabs and one articular sample. The association of several
      species was reported in several herds. These results are at variance with
      previous serological studies, which indicated a higher disease prevalence, and
      suggest that it could be necessary to use detection techniques such PCR to
      confirm the existence of contagious agalactia in goats.

PMID- 15964227
TI  - Purge NMR: effective and easy solvent suppression.
AB  - Presaturation utilizing relaxation gradients and echoes is an extremely easy and
      effective approach to solvent suppression in solution state nuclear magnetic
      resonance spectroscopy. The experiment produces flat baselines, excellent phase
      properties, and highly selective suppression that betters that of commonly used
      sequences. Furthermore, the only parameter that needs adjusting is the
      presaturation power, making it easy to implement even for non spectroscopists.
      Considering these factors, we envisage the approach will have wide spread
      applications.

PMID- 15964228
TI  - Single inhaler budesonide/formoterol in exacerbations of chronic obstructive
      pulmonary disease.
AB  - Inhaled bronchodilators, particularly short-acting inhaled beta(2)-agonists, and
      systemic glucocorticosteroids are effective treatments for acute exacerbations of
      chronic obstructive pulmonary disease (COPD). However, in the treatment of these
      episodes there may be some advantages to the longer-acting agents in that there
      will be prolonged bronchodilation. Moreover, high doses of systemic
      glucocorticosteroids are associated with a significant risk of side effects. In
      the last few years, evidence is mounting that nebulized budesonide and inhaled
      formoterol might be an alternative to oral prednisolone and short-acting beta(2)
      agonists, respectively, in the treatment of acute exacerbations of COPD.
      Interestingly, some new data suggest that a combination therapy with single
      inhaler containing budesonide and formoterol may be an alternative to traditional
      therapy in the treatment of acute exacerbations of this disorder. However, since
      individual studies are typically statistically underpowered and are remarkably
      heterogeneous with regard to their conclusions, larger studies are needed to
      confirm these preliminary findings and determine conclusively any impact of
      budesonide/formoterol combination in acutely ill COPD patients.

PMID- 15964229
TI  - Epigenetic variations in early cardiovascular performance and hematopoiesis can
      be explained by maternal and clutch effects in developing zebrafish (Danio
      rerio).
AB  - This is the first study to show maternal and clutch effects on early
      developmental parameters like blood cell concentration and cardiac performance
      (heart rate, stroke volume and cardiac output) in developing zebrafish larvae (2
      8 days post fertilization, dpf). Ten individuals per parental pair and
      developmental stage were analyzed. A pronounced interclutch variation of heart
      rate has been found in younger stages (2-4 dpf), while interclutch variation of
      heart rate was small in later stages (8 dpf). This effect was more pronounced in
      offspring from parental fish nourished with living food. The opposite effect was
      observed in interclutch variation of blood cell concentration. Here only older
      stages showed significant interclutch variations. Stroke volume and cardiac
      output had very small interclutch variations throughout all stages. Heart rate
      was strongly dependent with developmental stage in all groups. Nutritional
      maternal effects on heart performance and also in blood cell concentration could
      be detected in the offspring of parent animals either fed with flake food or with
      living food. Red blood cell count, calculated as a product from red blood cell
      concentration, was not significantly different in both feeding groups. The number
      of spawned eggs was not different. In summary, these data indicate that "clutch
      effects" caused by maternal and/or genetic influences can affect the
      developmental pattern of cardiac performance and blood cell concentration.

PMID- 15964230
TI  - The development of the pulmonary surfactant system in California sea lions.
AB  - Pulmonary surfactant has previously been shown to change during development, both
      in composition and function. Adult pinnipeds, unlike adult terrestrial mammals,
      have an altered lung physiology to cope with the high pressures associated with
      deep diving. Here, we investigated how surfactant composition and function
      develop in California sea lions (Zalophus californianus). Phosphatidylinositol
      was the major anionic phospholipid in the newborn, whereas phosphatidylglycerol
      was increased in the adult. This increase in phosphatidylglycerol occurred at the
      expense of phosphatidylinositol and phosphatidylserine. There was a shift from
      long chain and polyunsaturated phospholipid molecular species in the newborn to
      shorter chain and mono- and disaturated molecular species in the adult.
      Cholesterol and SP-B concentrations were also higher in the adult. Adult
      surfactant could reach a lower equilibrium surface tension, but newborn
      surfactant could reach a lower minimum surface tension. The composition and
      function of surfactant from newborn California sea lions suggest that this age
      group is similar to terrestrial newborn mammals, whereas the adult has a "diving
      mammal" surfactant that can aid the lung during deep dives. The onset of diving
      is probably a trigger for surfactant development in these animals.

PMID- 15964231
TI  - Changes in lipid composition of hepatocyte plasma membrane induced by overfeeding
      in duck.
AB  - This experiment was carried out to examine the influence of overfeeding ducks
      with corn on the lipid composition of hepatocyte plasma membrane. Seventy-day-old
      male Mule ducks (Cairina moschata x Anas platyrhynchos) were overfed with corn
      for 12.5 days in order to induce fatty livers. The cholesterol and phospholipid
      contents were approximately 50% higher in hepatocyte plasma membranes from fatty
      livers compared to those of lean livers obtained from non-overfed ducks. However,
      the cholesterol/phospholipids molar ratio did not differ between both groups.
      Overfeeding induced a significant change in phospholipid composition of
      hepatocyte plasma membrane with a decrease in phosphatidylcholine proportion and
      conversely an increase in phosphatidylethanolamine. The fatty acid profile of
      phospholipids was also altered. In fatty hepatocyte plasma membrane, the overall
      proportion of polyunsaturated fatty acids (PUFA) was decreased and this was due
      to the decrease of some of, but not all, the PUFA. In addition, the proportions
      of oleic acid and n-9 series unsaturated fatty acids were higher in fatty than in
      lean liver membranes. This study provides evidence that overfeeding with a
      carbohydrate-rich corn-based diet induces a de novo hepatic lipogenesis in Mule
      duck which predominates over dietary lipid intake to change the lipid composition
      of the hepatocyte plasma membrane.

PMID- 15964232
TI  - Evolutionarily conserved and divergent regulatory sequences in the fish rod opsin
      promoter.
AB  - Fish have multiple types and subtypes of opsin genes that are expressed in a
      highly regulated manner in retinal photoreceptor cells. In the rod opsin proximal
      promoter region (RPPR) of zebrafish (Danio rerio), the BAT 1 regulatory region
      contains highly conserved OTX (GATTA) and OTX-like (TATTA) sequences that can be
      recognized by the mammalian cone-rod homeobox (CRX) protein. However, binding of
      zebrafish crx to the OTX sequence has remained elusive. In contrast to the BAT 1
      region, the Ret 1 region, located approximately 20 bp upstream of the BAT 1
      region in mammals, is not conserved in zebrafish. In the Ret 1 region, even the
      core OTX-like sequence (AATTA sequence in mammals) is destructed. We show in this
      study that a region between Ret 1 and BAT 1 (denoted IRB, Inter-Ret 1-BAT 1) is
      highly conserved among fish species. Using electrophoretic mobility shift assay
      (EMSA), we show that zebrafish crx binds to the conserved OTX sequence and that
      the fish-specific IRB region specifically binds elements present in both retinal
      and brain nuclear extracts of zebrafish. These results imply that the regulatory
      mechanisms of opsin gene expression consist not only of evolutionarily conserved
      but also of divergent machinery among different animal taxa.

PMID- 15964233
TI  - Modeling, identification and nonlinear model predictive control of type I
      diabetic patient.
AB  - Patients with type I diabetes nearly always need therapy with insulin. The most
      desirable treatment would be to mimic the operation of a normal pancreas. In this
      work a patient affected with this pathology is modeled and identified with a
      neural network, and a control strategy known as Nonlinear Model Predictive
      Control is evaluated as an approach to command an insulin pump using the
      subcutaneous route. A method for dealing with the problems related with the
      multiple insulin injections simulation and a multilayer neural network
      identification of the patient model is presented. The controller performance of
      the proposed strategy is tested under charge and reference disturbances
      (setpoint). Simulating an initial blood glucose concentration of 250 mg/dl a
      stable value of 97.0 mg/dl was reached, with a minimum level of 76.1 mg/dl. The
      results of a simulated 50 g oral glucose tolerance test show a maximum glucose
      concentration of 142.6 mg/dl with an undershoot of 76.0 mg/dl. According to the
      simulation results, stable close-loop control is achieved and physiological
      levels are reached with reasonable delays, avoiding the undesirable low glucose
      levels. Further studies are needed in order to deal with noise and robustness
      aspects, issues which are out of the scope of this work.

PMID- 15964234
TI  - Acute myeloid leukemia: therapeutic impact of epigenetic drugs.
AB  - Acute myeloid leukemia (AML) is not a single disease but a group of malignancies
      in which the clonal expansion of various types of hematopoietic precursor cells
      in the bone marrow leads to perturbation of the delicate balance between self
      renewal and differentiation that is characteristic of normal hematopoiesis. An
      increasing number of genetic aberrations, such as chromosomal translocations that
      alter the function of transcription regulatory factors, has been identified as
      the cause of AML and shown to act by deregulating gene programming at both the
      genetic and epigenetic level. While the genetic aberrations occurring in acute
      myeloid leukemia are fairly well understood, we have only recently become aware
      of the epigenetic deregulation associated with leukemia, in particular with
      myeloid leukemias. The deposition of epigenetic "marks" on chromatin - post
      translational modifications of nucleosomal proteins and methylation of particular
      DNA sequences - is accomplished by enzymes, which are often embedded in multi
      subunit "machineries" that have acquired aberrant functionalities during
      leukemogenesis. These enzymes are targets for so-called "epi-drugs". Indeed,
      recent results indicate that epi-drugs may constitute an entirely novel type of
      anti-cancer drugs with unanticipated potential. Proof-of-principle comes from
      studies with histone deacetylase inhibitors, promising novel anti-cancer drugs.
      In this review we focus on the epigenetic mechanisms associated with acute
      myeloid leukemogenesis and discuss the therapeutic potential of epigenetic
      modulators such as histone deacetylase and DNA methyltransferase inhibitors.

PMID- 15964235
TI  - Investigation of cell cycle arrest effects of actinomycin D at G1 phase using
      proteomic methods in B104-1-1 cells.
AB  - Actinomycin D was previously reported as an inhibitor of Shc/Grb2 interaction in
      B104-1-1 cells. Actinomycin D arrested the cell cycle at the G1 phase at 1nM,
      which is about 10 times lower than the inhibition of Shc/Grb2 interactions in
      B104-1-1 cells. To evaluate other mechanisms of actinomycin D affected
      suppression of tumors and cell growth, except inhibition of Shc/Grb2
      interactions, we examined the proteomic expression profile by proteomic
      technology. We found up-regulation of MEKK3 and down-regulation of Hsp70
      expression from proteomic analysis, which is a very interesting observation
      because MEKK3 is strongly related with G1 arrest of cell cycle and Hsp70 is also
      involved in cell cycle regulation. These results indicate that the anti-tumor
      effects of actinomycin D is due to synergic effects of various proteins regulated
      by the compound including inhibition of the Shc/Grb2 interaction and other
      signaling pathways in the cytoplasm. Here we provide a mechanism-based
      explanation for growth inhibition by actinomycin D using proteomic technology.
      Thus, this approach may be a potentially useful method to reveal new mechanisms
      of active compounds or drugs with unknown cellular function.

PMID- 15964236
TI  - The SH2 domain containing inositol polyphosphate 5-phosphatase-2: SHIP2.
AB  - Phosphoinositides are membrane-bound signaling molecules that recruit, activate
      and localize target effectors to intracellular membranes regulating apoptosis,
      cell proliferation, insulin signaling and membrane trafficking. The SH2 domain
      containing inositol polyphosphate 5-phosphatase-2 (SHIP2) hydrolyzes
      phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) generating
      phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2). Overexpression of SHIP2
      inhibits insulin-stimulated phosphoinositide 3-kinase (PI3K) dependent signaling
      events. Analysis of diabetic human subjects has revealed an association between
      SHIP2 gene polymorphisms and type 2 diabetes mellitus. Genetic ablation of SHIP2
      in mice has generated conflicting results. SHIP2 knockout mice were originally
      reported to show lethal neonatal hypoglycemia resulting from insulin
      hypersensitivity, but in addition to inactivating the SHIP2 gene, the Phox2a gene
      was also inadvertently deleted. Another SHIP2 knockout mouse has now been
      generated which inactivates the SHIP2 gene but leaves Phox2a intact. These
      animals show normal insulin and glucose tolerance but are highly resistant to
      weight gain on high fat diets, exhibiting an obesity-resistant phenotype.
      Therefore, SHIP2 remains a significant therapeutic target for the treatment of
      both obesity and type 2 diabetes.

PMID- 15964237
TI  - Insulin-like growth factor-1 and muscle wasting in chronic heart failure.
AB  - Chronic heart failure is a clinical syndrome of cardiac origin, which affects
      various organ systems. It is associated with metabolic abnormalities leading to a
      catabolic syndrome in advanced stages of the disease. As in several other chronic
      diseases, skeletal muscle dysfunction and structural muscle abnormalities result
      in progressive muscle wasting and cachexia. These changes are accompanied by
      increased expression of proinflammatory cytokines, increased rate of apoptosis
      and activation of the proteolytic ubiquitin-proteasome pathway. Further, reduced
      expression of the local anabolic insulin-like growth factor-1 has been
      demonstrated in skeletal muscle of animals and patients with chronic heart
      failure. This suppression occurs in the presence of normal serum levels of
      insulin-like growth factor-1. In addition to catabolic effects of proinflammatory
      cytokines, these recent findings are consistent with reduced anabolism involving
      altered local insulin-like growth factor-1 levels in progressive muscle atrophy
      in chronic heart failure. This article describes local effects of insulin-like
      growth factor-1 on skeletal muscle function and morphology, its role in stem cell
      recruitment and muscle regeneration as well as its regulation in circumstances of
      muscle inflammation and wasting.

PMID- 15964238
TI  - Targeting the cell division cycle in cancer: CDK and cell cycle checkpoint kinase
      inhibitors.
AB  - The cyclin-dependent kinase (CDK) family of serine/threonine kinases regulate
      progression through each stage of the cell division cycle and as such are major
      targets for deregulation in cancer. This has led to the development of several
      small-molecule inhibitors of CDKs as potential therapeutic agents for the
      treatment of this disease. Progression through the cell cycle is also monitored
      at several positions known as cell cycle checkpoints, two of which occur during
      G1 and G2 in response to DNA damage. These are often defective in cancer, leading
      to the suggestion that inhibition of one or both of the cell cycle checkpoint
      kinases CHK1 and CHK2 may drive a cancer cell that already has defects in its
      cell cycle checkpoints towards death.

PMID- 15964239
TI  - Therapeutic apheresis in the Philippines.
AB  - The statistics for this report were obtained from a current survey being
      conducted by the Philippine Society for Hematology and Blood Transfusion for the
      purpose of organizing a national apheresis registry. Preliminary data coming from
      8 of 10 medical centers included 194 patients and 735 procedures from 1994 to
      2004. Eighty percent of patients belonged to ASFA indication Category I with a
      predominance of neurologic and hematologic disorders. Five most common
      indications were acute inflammatory demyelinating polyradiculoneuropathy (AIDP),
      multiple sclerosis (MS), thrombotic thrombocytopenic purpura (TTP),
      leucocytosis/thrombocytosis (L/T), and chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP). A rise from 5% to 20% was noted in procedures for
      TTP in this 10-year period. Favorable response is noted in the use of therapeutic
      apheresis (TA) for the removal of antibodies in presensitized patients prior to
      kidney transplantation to prevent rejection. Complete recovery was seen in 2 of 4
      patients with fulminant hepatic failure. Two patients with idiopathic
      thrombocytopenia (ITP) treated by plasma exchange were classified under Category
      IV due to unavailability of affinity columns. Negative results reported in
      controlled studies for the treatment of systemic lupus erythematosus account for
      the limited use of TA in this disease. Factors affecting the progress of TA in
      the country were cited. The organization of a national registry for apheresis may
      improve the practice of TA in the Philippines.

PMID- 15964240
TI  - WITHDRAWN: The platelet storage lesion: A comparative analysis of six
      leukoreduction processes in terms of biocompatability, microvesiculation,
      retention of prions, and generation/removal of biological response modifiers.
AB  - The Publisher regrets that this article was an accidental duplication of an
      article that has already been published in Transfus Apher Sci, 34 (1) 125 - 130,
      doi:10.1016/j.transci.2005.09.002. The duplicate article has therefore been
      withdrawn.

PMID- 15964241
TI  - Failure of bedside ABO testing is still the most common cause of incorrect blood
      transfusion in the Barcode era.
AB  - BACKGROUND AND OBJECTIVES: ABO-incompatible red blood cell (RBC) transfusions are
      a major risk in transfusion medicine. Identification of factors leading to this
      hazard is important to improve transfusion safety. MATERIAL AND METHODS: All
      consecutive erroneous ABO-incompatible transfusions occurring from January 1997
      to December 2004 at the Charite University Hospital in Berlin, Germany were
      analysed. RESULTS: A total of 343,432 RBC units were transfused, and eight
      patients erroneously received 13 ABO-incompatible RBC concentrates. The most
      frequent error was incorrect bedside testing (n=7). Intensive care treatment was
      required in two cases, but there were no fatal mistransfusions. Four patients had
      no or only mild reactions. CONCLUSION: Mistransfusions are still a considerable
      risk in transfusion medicine despite quality control systems and electronic data
      processing. An increase in transfusion safety may require the introduction of
      further systems, e.g. radio-frequency identification (RFID) tags.

PMID- 15964242
TI  - Longitudinal alteration of circulating dendritic cell subsets and its correlation
      with steroid treatment in patients with severe acute respiratory syndrome.
AB  - In this study, we found that 74 patients with severe acute respiratory syndrome
      (SARS) exhibited a rapid, dramatic decrease in numbers of circulating myeloid and
      plasmacytoid dendritic cells (mDCs and pDCs) during the first 2 weeks of illness
      (5.3- and 28.4-fold reductions for mDCs and pDCs compared with 25 healthy
      individuals, respectively), with slow return to normal cell numbers during
      convalescence (weeks 5-7 of illness on average). In addition, numbers of
      circulating CD4 and CD8 T cells exhibited milder reductions (2.1- and 1.8-fold at
      week 1) and earlier return to normal at a mean of weeks 3 and 4, respectively. A
      significant inverse correlation was found between numbers of DC and T-cell
      subsets and high-dose steroid treatment. Our novel findings thus suggest that the
      acute SARS-coronavirus infection probably contributes to the initial reduction of
      DC and T-cell subsets in blood, and that high-dose steroid administration may
      subsequently exacerbate and prolong low expression of the cell subsets. These
      findings will aid the framing of further studies of the immunopathogenesis of
      SARS.

PMID- 15964243
TI  - Intrabody applications in neurological disorders: progress and future prospects.
AB  - Single-chain Fv and single-domain antibodies retain the binding specificity of
      full-length antibodies, but they can be expressed as single genes in phage or
      yeast surface-display libraries, thus allowing efficient in vitro selection from
      a naive human repertoire. Selected genes can then be expressed intracellularly in
      mammalian cells as intrabodies, with the potential for alteration of the folding,
      interactions, modifications, or subcellular localization of their targets. These
      reagents have been developed as therapeutics against cancer and HIV. Since
      misfolded and accumulated intracellular proteins characterize a wide range of
      neurodegenerative disorders, they are also potentially useful intrabody targets.
      Here, we review the extension of intrabody technology to the nervous system, in
      which studies of Huntington's disease have been used to develop the approach, and
      anti-synuclein and -beta-amyloid strategies are in the early stages of
      development. Research on several other neurodegenerations, including Parkinson's,
      Alzheimer's, and prion diseases, provides support for the development of
      intrabodies directed against specific targets, or possibly against more common
      downstream targets, as novel therapeutics and as drug discovery tools.

PMID- 15964245
TI  - New insights into the mechanism of imposex induction in the dogwhelk Nucella
      lapillus.
AB  - In an attempt to clarify the mechanism(s) of tributyltin-mediated imposex
      induction in females of the neogastropod Nucella lapillus, dogwhelks collected in
      an almost imposex free population were exposed to several treatments for a 3
      month-period, and the effects on imposex induction and testosterone/estradiol
      levels were evaluated. As a positive control, tributyltin (50 ng TBT Sn/L)
      clearly induced imposex and led to a significant increase in the severity of the
      phenomenon. In contrast, although a selective P450 aromatase inhibitor
      (formestane at 0.3 mg/L) was capable of imposex induction, it failed to increase
      its severity. A vertebrate androgen receptor (AR) antagonist (cyproterone acetate
      at 1.25 mg/L) in combination with TBT completely blocked the imposex induction
      capacity of TBT. On the other hand, an estrogen receptor antagonist (tamoxifen at
      0.3 mg/L) rendered no effect. The determination of steroid levels in female
      specimens revealed that TBT induces an elevation of free testosterone (but not
      the total amount, free+esterified), while the co-administration of the anti
      androgen and TBT was able to rescue the increase of free testosterone levels.
      Despite a minor decrease in the amount of testosterone-fatty acid esters in the
      TBT group, significant differences in esterified testosterone were not found
      among treatments. On the contrary, free estradiol levels were elevated in the
      TBT, anti-androgens and TBT plus anti-androgens groups. These results indicate
      that free estradiol biosynthesis in TBT-exposed females does not seem to be
      affected. Overall, our results demonstrate that a selective aromatase inhibitor
      can induce imposex in N. lapillus but not to a similar extent of TBT, which may
      suggest the involvement of other mechanism in imposex induction, besides
      aromatase inhibition. Additionally, the study points to the involvement of AR
      receptors in imposex induction.

PMID- 15964244
TI  - A picornaviral 2A-like sequence-based tricistronic vector allowing for high-level
      therapeutic gene expression coupled to a dual-reporter system.
AB  - The 2A-like sequences from members of the picornavirus family were utilized to
      construct a tricistronic vector bearing the human iduronidase (IDUA) gene along
      with the firefly luciferase and DsRed2 reporter genes. The 2A-like sequences
      mediate a cotranslational cleavage event resulting in the release of each
      individual protein product. Efficient cleavage was observed and all three
      proteins were functional in vitro and in vivo, allowing for supratherapeutic IDUA
      enzyme levels and the coexpression of luciferase and DsRed2 expression, which
      enabled us to track gene expression.

PMID- 15964246
TI  - Dietary and water-borne Zn exposures affect energy reserves and subsequent Zn
      tolerance of Daphnia magna.
AB  - Enhanced tolerance of aquatic organisms to metal toxicity is one of the important
      issues of environmental monitoring programs. Determination of dominant uptake
      route(s) of metals may help to better predict the toxic effects posed by metals.
      This study aimed to investigate the importance of Zn uptake routes on tolerance
      and energy reserves of Daphnia magna. Neonates of D. magna were exposed to water
      borne zinc, dietary zinc (algae Pseudokichneriella subcapitata loaded with Zn) or
      to combination of both for 4 days. LC50 (48 h) values of Zn were considerably
      different from different zinc pre-exposures. Four-day pre-exposure of D. magna
      neonates produced enhanced tolerance to Zn toxicity. The lowest LC50 values were
      found in controls (48.2 microM) (no Zn added to their exposure medium and food)
      and after water-borne Zn pre-exposures (46.2 microM). The level of tolerance
      increased when dietary Zn was included in pre-exposures, reaching the highest
      level of LC50 value (70.8 microM) in the highest pre-exposure concentration of
      diet and water-borne combination experiment. The energy reserves of D. magna also
      varied significantly under different pre-exposure routes of zinc. In all cases,
      control animals contained lowest levels of protein, sugar and lipid. Likewise,
      they represented the lowest energy reserves. Protein levels were highest in the
      highest dietary Zn exposure, and lowest in the water-borne exposures. Highest and
      lowest sugar levels were measured in the lowest and highest water-borne Zn
      exposures, respectively. In contrast, lipid levels were higher in the higher Zn
      exposure of all exposure routes, the combination exposure resulting in highest
      lipid levels. The highest total energy reserve was measured in animals that lived
      in the highest Zn exposure of diet and water-borne combination experiment, mainly
      due to greater lipid reserves in algae reared in Zn containing media. Results
      suggest that the dietary exposure route should be considered carefully in natural
      monitoring studies, and be considered in regulatory assessments of zinc and
      population dynamics of cladocerans.

PMID- 15964247
TI  - Computerized physician order entry and medication errors: finding a balance.

PMID- 15964248
TI  - Aging, stress and the hippocampus.
AB  - Functional loss often occurs in many body systems (e.g., endocrine, cognitive,
      motor) with the passage of years, but there is great individual variation in the
      degree of compromise shown. The current focus on brain aging will continue
      because demographic trends indicate that the average lifespan will show a
      continued increase. There is increasing emphasis on understanding how aging
      contributes to a decline in brain functions, cognition being a prime example.
      This is due in part to the fact that dementias and other losses in brain function
      that sometimes accompany aging cause an obvious decline in the quality of life
      and these deficits are of more concern as the number of elderly increase. Stress
      also is a ubiquitous aspect of life and there is now a greater interest in
      understanding the role of stress and the stress response in brain aging. The key
      role of the hippocampus and its related brain structures in cognition, as well as
      in the feedback control of the response to stress, have made this brain area a
      logical focus of investigation for those interested in the impact of stress on
      brain aging. Here, we describe how the hippocampus changes with age and we
      examine the idea that age-related changes in the secretion patterns of the
      hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this
      structure. We also examine the proposal that stress, perhaps due to compromised
      HPA axis function, can contribute to hippocampal aging through exposure to
      excessive levels of glucocorticoids. The aging hippocampus does not appear to
      suffer a generalized loss of cells or synapses, although atrophy of the structure
      may occur in humans. Thus, age-related cognitive impairments are likely related
      to other neurobiological alterations that could include changes in the signaling,
      information encoding, plasticity, electrophysiological or neurochemical
      properties of neurons or glia. Although excessive levels of glucocorticoids are
      able to interfere with cognition, as well as hippocampal neuronal integrity, and
      aging is sometimes accompanied by an increase in these steroids because of
      inadequate feedback control of the HPA axis, none of these are a foregone
      consequence of aging. The general preservation of cells and the plastic potential
      of the hippocampus provide a focus for the development of pharmacological,
      nutritive or lifestyle strategies to combat age-related declines in the
      hippocampus as well as other brain areas.

PMID- 15964249
TI  - Xenopus CENP-A assembly into chromatin requires base excision repair proteins.
AB  - CENP-A is an essential histone H3 variant found in all eukaryotes examined to
      date. To begin to determine how CENP-A is assembled into chromatin, we developed
      a binding assay using sperm chromatin in cell-free extract derived from Xenopus
      eggs. Our data suggest that the catalytic activities of an unidentified
      deoxycytidine deaminase and UNG2, a uracil DNA glycosylase, are involved in CENP
      A assembly. In support of this model, inhibiting deoxycytidine deaminase with
      zebularine, or uracil DNA glycosylase with Ugi, uracil or UTP results in a lack
      of detectable CENP-A on sperm DNA. Conversely, inducing DNA damage increases the
      level of CENP-A detected on sperm chromatin. Our data suggest that base excision
      repair may be involved in assembly of this histone H3 variant.

PMID- 15964250
TI  - P-glycoprotein expression increases ATP release in respiratory cystic fibrosis
      cells.
AB  - P-glycoprotein (Pgp) is a well-defined ATP-binding cassette (ABC) protein and a
      close relative of cystic fibrosis transmembrane conductance regulator (CFTR),
      whose dysfunction causes cystic fibrosis (CF). It is postulated that Pgp can
      complement deficient CFTR functions because of structural and functional
      homologies. One of the most relevant functions appears to be the regulation of
      ATP release, which influences mucociliary clearance in respiratory epithelia by
      nucleotide receptor stimulation. However, mechanisms involved in ATP secretion
      remain a controversial issue. In the present study, CF epithelial cells
      (sigmaCFTE29o) were transduced with the retroviral vector MP1m encoding Pgp, and
      thus, a stable Pgp-overexpressing CF cell line (sigmaCFTE29oPgp) was established
      and used for studies of hypothesized CFTR complementation. In addition,
      overexpression of native Pgp in sigmaCFTE29o could also be achieved by long-term
      treatment with colchicine, a drug, which may be of great interest in CF therapy.
      We confirmed that overexpression of Pgp causes a significant increase in cellular
      ATP release, which could even be enhanced by stimulation with hypoosmolar medium.
      A potential clinical benefit is discussed.

PMID- 15964251
TI  - The spatial and temporal heterogeneity of regional ventilation: comparison of
      measurements by two high-resolution methods.
AB  - High-resolution estimates of ventilation distribution in normal animals utilizing
      deposition of fluorescent microsphere aerosol (FMS technique) demonstrate
      substantial ventilation heterogeneity, but this finding has not been confirmed by
      an independent method. Five supine anesthetized sheep were used to compare the
      spatial and temporal heterogeneity of regional ventilation measured by both the
      FMS technique and by a ventilation model utilizing the data from computed
      tomography images of xenon gas washin (CT/Xe technique). An aerosol containing 1
      microm fluorescent microspheres (FMS) was administered via a mechanical
      ventilator delivering a 2-s end-inspiration hold during each breath. Following
      the aerosol administration, sequential CT images of a transverse lung slice were
      acquired during each end-inspiration hold during washin of a 65% Xenon/35% oxygen
      gas mixture (CT/Xe technique). Four paired FMS and CT/Xe measurements were done
      at 30 min intervals, after which the animals were sacrificed. The lungs were
      extracted, air-dried and sliced in 1cm transverse sections. The lung section
      corresponding to the CT image was cut into 1 cm3 cubes, with notation of spatial
      coordinates. The individual cubes were soaked in solvent and the four fluorescent
      signals were measured with a fluorescence spectrophotometer. The color signals
      were normalized by the mean signal for all pieces and taken as the FMS estimate
      of ventilation heterogeneity. The CT images were clustered into 1 cm3 voxels and
      the rate of increase in voxel density was used to calculate voxel ventilation
      utilizing the model of . The regional ventilation voxel measurements were
      normalized by the mean value to give a CT/Xe estimate of ventilation
      heterogeneity comparable to the normalized FMS measurements. The overall of
      heterogeneity of ventilation at the 1 cm3 level of resolution was comparable by
      both techniques, with substantial differences among animals (coefficient of
      variation ranging from 37% to 74%). The repeated within-animal measurements by
      both techniques gave consistent values. Both techniques showed comparable large
      scale distribution of regional ventilation in the caudal lobes of the supine
      animals. There were appreciable differences in the temporal variability of
      ventilation among animals. This study provides an independent confirmation of the
      scale-dependent heterogeneity of ventilation described by previous FMS aerosol
      studies of ventilation heterogeneity.

PMID- 15964252
TI  - Differential effect of sleep-wake states on lingual and dorsal neck muscle
      activity in rats.
AB  - Postural tone is reduced during slow-wave sleep (SWS) and absent during rapid eye
      movement sleep (REMS). In obstructive sleep apnea subjects, upper airway dilating
      muscles, including those of the tongue, show a similar pattern; this contributes
      to sleep-related airway obstructions. However, in healthy subjects, state
      dependent changes in the activity of pharyngeal muscles are variable. In seven
      chronically instrumented Sprague-Dawley rats, an animal model used to study sleep
      and sleep-disordered breathing, we quantified lingual and postural muscle
      activity across the sleep-wake states by measuring the root mean square levels of
      the electromyograms (EMG) in successive 10s intervals collected during 2h of
      recording at a constant circadian time (1-3p.m.). The nuchal EMG was low and
      steady during SWS and further reduced with occasional twitches during REMS. In
      contrast, the mean lingual EMG during SWS was only 5.9+/-1.6% (S.E.) of its mean
      in wakefulness, and during REMS, it increased to 46+/-15% (S.E.) (p<0.03) due to
      the appearance of phasic bursts, the intensity of which progressively increased.
      The lingual and nuchal activities also had different time courses during state
      transitions. In obstructive sleep apnea subjects, the sleep-wake changes in the
      activity of pharyngeal muscles may become similar to those in postural muscles as
      a result of pharyngeal tone adaptations to the disorder.

PMID- 15964253
TI  - Magnetic resonance evaluation of fetal ventriculomegaly-associated congenital
      malformations and lesions.
AB  - Fetal MRI provides diagnostic quality images of the brain which permit
      differentiation between the various etiologies of ventriculomegaly:
      hydrocephalus, congenital malformation, and destructive processes.

PMID- 15964254
TI  - Risk factors for clinical stress fractures in male military recruits: a
      prospective cohort study.
AB  - This prospective study was aimed at evaluating risk factors for symptomatic
      stress fractures among 179 Finnish male military recruits, aged 18 to 20 years.
      The subjects were studied in the very beginning of the military service of 6 to
      12 months in summer. Bone mineral content (BMC) and density (BMD) were measured
      by dual energy X-ray absorptiometry (DXA) at the lumbar spine and at the hip and
      heel ultrasound investigation was performed. Blood was sampled for determination
      of serum total and free testosterone, total and free estradiol, sex hormone
      binding globulin (SHBG), procollagen type I N propeptide, total and carboxylated
      osteocalcin, tartrate-resistant acid phosphatase 5b, 25-hydroxyvitamin D (25
      OHD), and intact parathyroid hormone (iPTH), as well as for studying the XbaI and
      PvuII polymorphisms of the estrogen receptor gene and the CAG repeat polymorphism
      of the androgen receptor gene. Urine was collected for the determination of N
      terminal cross-linking telopeptide of type I collagen. Muscle strength was
      measured and Cooper's test was performed. Current exercise, smoking, calcium
      intake, and alcohol consumption were recorded using a questionnaire. During
      military service, 15 men experienced a stress fracture, diagnosed with X-ray in
      14 and with nuclear magnetic resonance in one man. Those who experienced a
      fracture were taller than those who did not (P = 0.047). The result of Cooper's
      test was worse in the fracture group than in the non-fracture group (P = 0.026).
      Femoral neck and total hip BMC and BMD, adjusted for age, weight, height,
      exercise, smoking, and alcohol and calcium intake were lower (P = 0.021-0.041)
      for the fracture group. Stress fractures associated with higher iPTH levels (P =
      0.022) but not with lower 25-OHD levels. Bone turnover markers as well as sex
      hormone and SHBG levels were similar for men with and without stress fracture.
      There was no difference in the genetic analyses between the groups. In
      conclusion, tall height, poor physical conditioning, low hip BMC and BMD, as well
      as high serum PTH level are risk factors for stress fractures in male Finnish
      military recruits. Given the poor vitamin D status of young Finnish men,
      intervention studies of vitamin D supplementation to lower serum PTH levels and
      to possibly reduce the incidence of stress fractures are warranted.

PMID- 15964256
TI  - Thrombin mediated migration of osteogenic cells.
AB  - Given that thrombin is ubiquitously expressed at sites of vascular injury, and
      that osteogenic cells express receptors for thrombin, we questioned whether
      thrombin could attract osteogenic cells to a bony wound. Using a scratch wound
      assay, thrombin stimulated a significant increase in migration of osteogenic
      cultures of primary marrow cells. This effect was dependent on thrombin
      proteolytic activity; however, thrombin was unable to stimulate the migration of
      a more differentiated marrow-derived osteogenic cell line. To better understand
      the role of thrombin in osteoprogenitor migration, we developed an
      osteoprogenitor migration assay that combines a modified Boyden chamber with a
      bone nodule assay. Primary cells that migrated through the transwell filter in
      the presence of thrombin formed significantly more bone nodules compared to the
      condition without thrombin. This was not due to proliferation or differentiation
      effects of thrombin. In contrast, thrombin was unable to stimulate an increase in
      the number of nodules for the more differentiated osteogenic cell line. Thus, our
      results suggest that thrombin exhibits differential motogenic effects on
      osteogenic cells depending on their differentiation state. The cell
      migration/bone nodule assay described here is the first assay that can be
      specifically used to examine the effects of factors on the migration of
      osteoprogenitor cells, particularly those derived from primary populations.

PMID- 15964255
TI  - Mapping bone interstitial fluid movement: displacement of ferritin tracer during
      histological processing.
AB  - Bone interstitial fluid flow is thought to play a fundamental role in the
      mechanical stimulation of bone cells, either via shear stresses or cytoskeletal
      deformations. Recent evidence indicates that osteocytes are surrounded by a fiber
      matrix that may be involved in the mechanotransduction of external stimuli as
      well as in nutrient exchange. In our previous tracer studies designed to map how
      different-sized molecules travel through the bone porosities, we found that
      injected ferritin was confined to blood vessels and did not pass into the
      mineralized matrix. However, other investigators have shown that ferritin forms
      halo-shaped labeling that enters the mineralized matrix around blood vessels.
      This labeling is widely used to explain normal interstitial fluid movement in
      bone; in particular, it is said to demonstrate bulk centrifugal interstitial
      fluid movement away from a highly pressurized vascular porosity. In addition,
      appositional ferritin fronts are said to demonstrate centrifugal interstitial
      fluid movement from the medullary canal to the periosteal surface. The purpose of
      this study was to investigate the conflicting ferritin labeling results by
      evaluating the role of different histological processes in the formation of
      ferritin "halos." Ferritin was injected into the rat vasculature and allowed to
      circulate for 5 min. Samples obtained from tibiae were reacted for different
      times with Perl's reagent and then were either paraffin-embedded or sectioned
      with a cryostat. Halo-like labeling surrounding vascular pores was found in all
      groups, ranging from 1.2-3.9% for the samples treated with the shortest
      histological processes (unembedded, frozen sections) to 5.6-15% for the samples
      treated with the longest histological processes (paraffin-embedded sections).
      These results indicate that different histological processing methods are able to
      create ferritin "halos," with some processing methods allowing more
      redistribution of the ferritin tracer than others. Based on these results and the
      fact that "halo" labeling has not been found with any other tracer, as we seek to
      further delineate the movement of interstitial fluid and the role it plays in
      bone mechanotransduction, we believe that ferritin "halo" labeling should not be
      used to demonstrate physiological bone interstitial fluid flow.

PMID- 15964257
TI  - Which expert should I believe?

PMID- 15964258
TI  - Calcineurin.

PMID- 15964259
TI  - How effective were mangroves as a defence against the recent tsunami?
AB  - Whether or not mangroves function as buffers against tsunamis is the subject of
      in-depth research, the importance of which has been neglected or underestimated
      before the recent killer tsunami struck. Our preliminary post-tsunami surveys of
      Sri Lankan mangrove sites with different degrees of degradation indicate that
      human activity exacerbated the damage inflicted on the coastal zone by the
      tsunami.

PMID- 15964260
TI  - A new mode of information transfer in foraging bumblebees?

PMID- 15964261
TI  - Photoperiod differentially regulates gene expression rhythms in the rostral and
      caudal SCN.

PMID- 15964262
TI  - Visual cortex: how are faces and objects represented?
AB  - The way in which information about complex objects and faces is represented in
      visual cortex is controversial. One model posits that information is processed in
      modules, highly specialized for different categories of objects; an opposing
      model appeals to a distributed representation across a large network of visual
      areas. A recent paper uses a novel imaging technique to address this controversy.

PMID- 15964263
TI  - Candida albicans biofilms: more than filamentation.
AB  - Candida albicans is the fungal species most commonly associated with biofilm
      formation in immunosuppressed patients. Recent work offers a fresh new look at
      the role of filamentation in C. albicans biofilm formation, and describes the
      application of a powerful tool for the molecular dissection of these important
      developmental processes.

PMID- 15964264
TI  - Circadian biology: clocks within clocks.
AB  - A small cluster of approximately 20,000 neurons in the ventral hypothalamus
      provide the body with key time-keeping signals and drive circadian rhythms. This
      circadian clock exhibits surprisingly complex substructures, with inputs from the
      retina, and outputs to other brain structures. Rather little is known of the
      neurotransmitters involved, or their regulation.

PMID- 15964265
TI  - miRNAs: whys and wherefores of miRNA-mediated regulation.
AB  - MiRNAs are assumed to be important in animal development and physiology, but
      their specific roles in vivo are still poorly understood. New bioinformatic and
      genetic studies are setting the stage for unraveling the specific biological
      functions of miRNAs.

PMID- 15964266
TI  - Cyclin degradation: don't mes(s) with meiosis.
AB  - Cyclin degradation is required for exit from mitosis and enables a new round of
      DNA replication in the subsequent S phase. A recent study in fission yeast shows
      that, during exit from meiosis I, the Mes1 protein partially inhibits cyclin
      degradation and thereby allows entry into meiosis II without an intervening S
      phase.

PMID- 15964267
TI  - Language emergence: clues from a new bedouin sign.
AB  - A sign language has emerged among three generations of deaf people and their
      families in a Bedouin community in the Negev desert. This newly reported case
      sheds light on the minimal environmental social factors required to generate a
      language.

PMID- 15964268
TI  - Virus evolution: fitting lifestyles to a T.
AB  - The structure of a double-stranded RNA virus outer shell has revealed unexpected
      similarities with virions of positive-strand RNA viruses. These similarities
      intersect with emerging parallels in RNA replication to create intriguing
      evolutionary possibilities.

PMID- 15964269
TI  - Somite formation: where left meets right.
AB  - Somites are the bilaterally symmetric embryonic precursors of the vertebrate
      skeleton and axial muscle. Three recent studies reveal that somites form
      asymmetrically in the absence of retinoic acid signaling. These results uncover
      an unexpected relationship between somitogenesis and left-right patterning, and
      suggest that bilateral somite formation is regulated along the left-right axis.

PMID- 15964270
TI  - Circadian clocks: translation.
AB  - One of the big questions in biological rhythms research is how a stable and
      precise circa-24 hour oscillation is generated on the molecular level. While
      increasing complexity seemed to be the key, a recent report suggests that circa
      24 hour rhythms can be generated by just four molecules incubated in a test tube.

PMID- 15964271
TI  - DNA repair: how to PIKK a partner.
AB  - In eukaryotes, members of the phosphoinositide-3-kinase-related protein kinase
      (PIKK) family co-ordinate the cellular response to DNA damage. But how do these
      important kinases detect DNA damage and relay this information to the DNA repair
      and checkpoint machinery?

PMID- 15964272
TI  - Polo-like kinase 1 creates the tension-sensing 3F3/2 phosphoepitope and modulates
      the association of spindle-checkpoint proteins at kinetochores.
AB  - BACKGROUND: In mitosis, a mechanochemical system recognizes tension that is
      generated by bipolar microtubule attachment to sister kinetochores. This is
      translated into multiple outputs including the stabilization of microtubule
      attachments, changes in kinetochore protein dynamics, and the silencing of the
      spindle checkpoint. How kinetochores sense tension and translate this into
      various signals represent critical unanswered questions. The kinetochores of
      chromosomes not under tension are specifically phosphorylated at an epitope
      recognized by the 3F3/2 monoclonal antibody. Determining the kinase that
      generates the 3F3/2 phosphoepitope at kinetochores should reveal an important
      component of this system that regulates mitotic progression. RESULTS: We
      demonstrate that Polo-like kinase 1 (Plk1) creates the 3F3/2 phosphoepitope on
      mitotic kinetochores. In a permeabilized in vitro cell system, the depletion of
      Xenopus Plk1 from M phase extract leads to the loss of 3F3/2 kinase activity.
      Purified recombinant Plk1 is sufficient to generate the 3F3/2 phosphoepitope in
      this system. Using siRNA, we show that the reduction of Plk1 protein levels
      significantly diminishes 3F3/2 phosphoepitope expression at kinetochores. The
      consensus phosphorylation sites of Plk1 show strong similarity to the 3F3/2
      phosphoepitope sequence determined by phosphopeptide mapping. The inhibition of
      Plk1 by siRNA alters the normal kinetochore association of Mad2, Cenp-E,
      Hec1/Ndc80, Spc24, and Cdc20 and induces a spindle-checkpoint-mediated mitotic
      arrest. CONCLUSIONS: Plk1 generates the 3F3/2 phosphoepitope at kinetochores that
      are not under tension and contributes to the normal kinetochore association of
      several key proteins important in checkpoint signaling. Mechanical tension
      regulates Plk1 accumulation at kinetochores and possibly its kinase activity.

PMID- 15964273
TI  - Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of
      ciliary-disease genes.
AB  - BACKGROUND: The centriole is one of the most enigmatic organelles in the cell.
      Centrioles are cylindrical, microtubule-based barrels found in the core of the
      centrosome. Centrioles also act as basal bodies during interphase to nucleate the
      assembly of cilia and flagella. There are currently only a handful of known
      centriole proteins. RESULTS: We used mass-spectrometry-based MudPIT
      (multidimensional protein identification technology) to identify the protein
      composition of basal bodies (centrioles) isolated from the green alga
      Chlamydomonas reinhardtii. This analysis detected the majority of known centriole
      proteins, including centrin, epsilon tubulin, and the cartwheel protein BLD10p.
      By combining proteomic data with information about gene expression and
      comparative genomics, we identified 45 cross-validated centriole candidate
      proteins in two classes. Members of the first class of proteins (BUG1-BUG27) are
      encoded by genes whose expression correlates with flagellar assembly and which
      therefore may play a role in ciliogenesis-related functions of basal bodies.
      Members of the second class (POC1-POC18) are implicated by comparative-genomics
      and -proteomics studies to be conserved components of the centriole. We confirmed
      centriolar localization for the human homologs of four candidate proteins. Three
      of the cross-validated centriole candidate proteins are encoded by orthologs of
      genes (OFD1, NPHP-4, and PACRG) implicated in mammalian ciliary function and
      disease, suggesting that oral-facial-digital syndrome and nephronophthisis may
      involve a dysfunction of centrioles and/or basal bodies. CONCLUSIONS: By
      analyzing isolated Chlamydomonas basal bodies, we have been able to obtain the
      first reported proteomic analysis of the centriole.

PMID- 15964275
TI  - Directed attention eliminates 'change deafness' in complex auditory scenes.
AB  - In natural environments that contain multiple sound sources, acoustic energy
      arising from the different sources sums to produce a single complex waveform at
      each of the listener's ears. The auditory system must segregate this waveform
      into distinct streams to permit identification of the objects from which the
      signals emanate [1]. Although the processes involved in stream segregation are
      now reasonably well understood [1, 2 and 3], little is known about the nature of
      our perception of complex auditory scenes. Here, we examined complex scene
      perception by having listeners detect a discrete change to an auditory scene
      comprising multiple concurrent naturalistic sounds. We found that listeners were
      remarkably poor at detecting the disappearance of an individual auditory object
      when listening to scenes containing more than four objects, but they performed
      near perfectly when their attention was directed to the identity of a potential
      change. In the absence of directed attention, this "change deafness" [4] was
      greater for objects arising from a common location in space than for objects
      separated in azimuth. Change deafness was also observed for changes in object
      location, suggesting that it may reflect a general effect of the dependence of
      human auditory perception on attention.

PMID- 15964274
TI  - Melanopsin-dependent photoreception provides earliest light detection in the
      mammalian retina.
AB  - BACKGROUND: The visual system is now known to be composed of image-forming and
      non-image-forming pathways. Photoreception for the image-forming pathway begins
      at the rods and cones, whereas that for the non-image-forming pathway also
      involves intrinsically photosensitive retinal ganglion cells (ipRGCs), which
      express the photopigment melanopsin. In the mouse retina, the rod and cone
      photoreceptors become light responsive from postnatal day 10 (P10); however, the
      development of photosensitivity of the ipRGCs remains largely unexplored.
      RESULTS: Here, we provide direct physiological evidence that the ipRGCs are light
      responsive from birth (P0) and that this photosensitivity requires melanopsin
      expression. Interestingly, the number of ipRGCs at P0 is over five times that in
      the adult retina, reflecting an initial overproduction of melanopsin-expressing
      cells during development. Even at P0, the ipRGCs form functional connections with
      the suprachiasmatic nucleus, as assessed by light-induced Fos expression.
      CONCLUSIONS: The findings suggest that the non-image-forming pathway is
      functional long before the mainstream image-forming pathway during development.

PMID- 15964276
TI  - Generation of cloned mice by direct nuclear transfer from natural killer T cells.
AB  - Cloning mammals by nuclear transfer (NT) remains inefficient. One fundamental
      question is whether clones have really been derived from differentiated cells
      rather than from rare stem cells present in donor-cell samples. To date, cells,
      such as mature lymphocytes, with genetic differentiation markers have been cloned
      to generate mice only via a two-step NT involving embryonic stem (ES) cell
      generation and tetraploid complementation [1, 2 and 3]. Here, we show that the
      genome of a unique T-cell population, natural killer T (NKT) cells, can be fully
      reprogrammed by a single-step NT. The pups and their placentas possessed the
      rearranged TCR loci specific for NKT cells. The NKT-cell-cloned embryos had a
      high developmental potential in vitro: Most (71%) developed to the
      morula/blastocyst stage, in marked contrast to embryos from peripheral blood T
      cells (12%; p < 1 x 10(-25)). Furthermore, ES cell lines were efficiently
      established from these NKT-cell blastocysts. These findings clearly indicate a
      high level of plasticity in the NKT-cell genome. Thus, differentiation of the
      genome is not always a barrier to NT cloning for either reproductive or
      therapeutic purposes, so we can now postulate that at least some mammals cloned
      to date have indeed been derived from differentiated donor cells.

PMID- 15964277
TI  - Disorders of agency in schizophrenia correlate with an inability to compensate
      for the sensory consequences of actions.
AB  - Psychopathological symptoms in schizophrenia patients suggest that the concept of
      self might be disturbed in these individuals [1]. Delusions of influence make
      them feel that someone else is guiding their actions, and certain kinds of their
      hallucinations seem to be misinterpretations of their own inner voice as an
      external voice, the common denominator being that self-produced information is
      perceived as if coming from outside. If this interpretation were correct, we
      might expect that schizophrenia patients might also attribute the sensory
      consequences of their own eye movements to the environment rather than to
      themselves, challenging the percept of a stable world. Indeed, this seems to be
      the case because we found a clear correlation between the strength of delusions
      of influence and the ability of schizophrenia patients to cancel out such self
      induced retinal information in motion perception. This correlation reflects
      direct experimental evidence supporting the view that delusions of influence in
      schizophrenia might be due to a specific deficit in the perceptual compensation
      of the sensory consequences of one's own actions [1, 2, 3, 4, 5 and 6].

PMID- 15964278
TI  - Perception of the consequences of self-action is temporally tuned and event
      driven.
AB  - It has been proposed that in order to increase the salience of sensations with an
      external cause, sensations that are predictable based on one's own actions are
      attenuated [1 and 2]. This may explain why self-imposed tickle [3 and 4] or
      constant forces [5] are perceived as less intense than the same stimuli
      externally imposed. Here, subjects used their right index finger to tap a force
      sensor mounted above their left index finger. When a motor generated a tap on the
      left finger synchronously with the right tap, simulating contact between the
      fingers, the perception of force in the left finger was attenuated compared to
      the same tap experienced during rest. Attenuation gradually reduced as the left
      tap was either delayed or advanced relative to the active right tap. However, no
      attenuation was seen to left taps triggered by right-finger movements that
      stopped above or passed wide of the sensor. We conclude that there is a window of
      sensory attenuation that is broadly temporally tuned and centered on the time at
      which the fingers would normally make contact. That is, predictive tactile
      sensory attenuation is linked to specific external events arising from movement
      rather than to the movement per se.

PMID- 15964279
TI  - An importin alpha homolog, MOS6, plays an important role in plant innate
      immunity.
AB  - Plant disease resistance is the consequence of an innate defense mechanism
      mediated by Resistance (R) genes [1]. The conserved structure of one class of R
      protein is reminiscent of Toll-like receptors (TLRs) and Nucleotide binding
      oligomerization domain (NOD) proteins-immune-response perception modules in
      animal cells [2, 3, and 4]. The Arabidopsis snc1 (suppressor of npr1-1,
      constitutive, 1) mutant contains a mutation in a TIR-NBS-LRR-type of R gene that
      renders resistance responses constitutively active without interaction with
      pathogens [5]. Few components of the downstream signaling network activated by
      snc1 are known. To search for regulators of R-gene-mediated resistance, we
      screened for genetic suppressors of snc1. Three alleles of the mutant mos6
      (modifier of snc1, 6) partially suppressed constitutive-resistance responses and
      immunity to virulent pathogens in snc1. Furthermore, the mos6-1 single mutant
      exhibited enhanced disease susceptibility to a virulent oomycete pathogen. MOS6,
      identified by positional cloning, encodes importin alpha3, one of eight alpha
      importins in Arabidopsis [6]. alpha importins mediate the import of specific
      proteins across the nuclear envelope. We previously reported that MOS3, a protein
      homologous to human nucleoporin 96, is required for constitutive resistance in
      snc1 [7]. Our data highlight an essential role for nucleo-cytoplasmic
      trafficking, especially protein import, in plant innate immunity.

PMID- 15964280
TI  - Structurally conserved interaction of Lgl family with SNAREs is critical to their
      cellular function.
AB  - The Lethal giant larvae (Lgl) tumor suppressor family is conserved from yeast to
      mammals and plays a critical yet controversial role in cell polarity. Studies on
      Drosophila Lgl suggest that its function in polarity is through regulation of the
      acto-myosin cytoskeleton. In contrast, studies on the yeast Lgl homologs,
      Sro7/Sro77, suggest a function in exocytosis through interaction with the t-SNARE
      Sec9. Using yeast/mammalian Lgl chimeras, we demonstrate that the overall
      architecture of Lgl proteins is highly conserved and that the C-terminal domain
      is the major site of SNARE interaction within both yeast and mammalian homologs.
      Importantly, we find that the ability of Lgl chimeras to function as the only
      source of Lgl in yeast correlates precisely with the ability to interact with the
      yeast t-SNARE. We report a novel interaction between Sro7 and the yeast myosin V,
      Myo2. However, we find that interactions with either Myo2 or Myo1 (myosin II)
      cannot account for the dramatic functional differences observed for these
      chimeras in yeast. These results provide the first demonstration that the
      interaction of an Lgl family member with a specific effector is critical to its
      function in vivo. These data support the model that the Lgl family functions in
      cell polarity, at least in part, by regulating SNARE-mediated membrane delivery
      events at the cell surface.

PMID- 15964281
TI  - Ion-channel noise places limits on the miniaturization of the brain's wiring.
AB  - The action potential (AP) is transmitted by the concerted action of voltage-gated
      ion channels. Thermodynamic fluctuations in channel proteins produce
      probabilistic gating behavior, causing channel noise. Miniaturizing signaling
      systems increases susceptibility to noise, and with many cortical, cerebellar,
      and peripheral axons <0.5 mum diameter [1, 2 and 3], channel noise could be
      significant [4 and 5]. Using biophysical theory and stochastic simulations, we
      investigated channel-noise limits in unmyelinated axons. Axons of diameter below
      0.1 microm become inoperable because single, spontaneously opening Na channels
      generate spontaneous AP at rates that disrupt communication. This limiting
      diameter is relatively insensitive to variations in biophysical parameters (e.g.,
      channel properties and density, membrane conductance and leak) and will apply to
      most spiking axons. We demonstrate that the essential molecular machinery can, in
      theory, fit into 0.06 microm diameter axons. However, a comprehensive survey of
      anatomical data shows a lower limit for AP-conducting axons of 0.08-0.1 microm
      diameter. Thus, molecular fluctuations constrain the wiring density of brains.
      Fluctuations have implications for epilepsy and neuropathic pain because changes
      in channel kinetics or axonal properties can change the rate at which channel
      noise generates spontaneous activity.

PMID- 15964282
TI  - Regulation of cell-surface genes and biofilm formation by the C. albicans
      transcription factor Bcr1p.
AB  - The impact of many microorganisms on their environment depends upon their ability
      to form surface bound communities called biofilms [1]. Biofilm formation on
      implanted medical devices has severe consequences for human health by providing
      both a portal of entry and a sanctuary for invasive bacterial and fungal
      pathogens [1 and 2]. Biofilm regulators and adherence molecules are extensively
      defined for many bacterial pathogens [3, 4, and 5], but not for fungal pathogens
      such as Candida albicans. Elongated filaments called hyphae are a prominent
      feature of C. albicans biofilms, and known genes that promote biofilm formation
      are required for hyphal development [2, 6, 7 and 8]. From a new library of
      transcription-factor mutants, we identify Bcr1p, a zinc finger protein required
      for formation of biofilms but not hyphae. Expression analysis shows that Bcr1p
      activates cell-surface protein and adhesin genes, including several induced
      during hyphal development. BCR1 expression depends upon the hyphal regulator
      Tec1p. Thus, BCR1 is a downstream component of the hyphal regulatory network that
      couples expression of cell-surface genes to hyphal differentiation. Our results
      indicate that hyphal cells are specialized to present adherence molecules that
      support biofilm integrity.

PMID- 15964284
TI  - Family planning for obese women: challenges and opportunities.

PMID- 15964283
TI  - The Drosophila fragile X mental retardation protein controls actin dynamics by
      directly regulating profilin in the brain.
AB  - Loss of Fragile X mental retardation protein (FMRP) function causes the highly
      prevalent Fragile X syndrome [1 and 2]. Identifying targets for the RNA binding
      FMRP is a major challenge and an important goal of research into the pathology of
      the disease. Perturbations in neuronal development and circadian behavior are
      seen in Drosophila dfmr1 mutants. Here we show that regulation of the actin
      cytoskeleton is under dFMRP control. dFMRP binds the mRNA of the Drosophila
      profilin homolog and negatively regulates Profilin protein expression. An
      increase in Profilin mimics the phenotype of dfmr1 mutants. Conversely,
      decreasing Profilin levels suppresses dfmr1 phenotypes. These data place a new
      emphasis on actin misregulation as a major problem in fmr1 mutant neurons.

PMID- 15964285
TI  - The morning after on the internet: usage of and questions to the emergency
      contraception website.
AB  - OBJECTIVE: The objective of this study is to understand the concerns of users of
      a medical information website on emergency contraception (EC). METHODS: This
      study analyzes e-mails sent to the EC website over a 5-year period. It also
      reports on the website's most frequently viewed pages using Microsoft Site Server
      Analysis. RESULTS: Of the 7022 e-mails received, 29% did not contain questions
      about EC. The remaining e-mails reveal that EC users are concerned with how to
      use EC (23%), side effects (21%), pregnancy (17%), whether EC is needed in a
      given situation (14%), EC access (8%), EC effectiveness (4%) and how EC works
      (3%). Analysis of website page visits shows that visitors were chiefly interested
      in how to use EC and how to interpret bleeding after EC use. CONCLUSION: The e
      mails point to the need for further research on EC-related questions that cannot
      be answered with the extant medical literature but are of concern to patients -
      questions such as bleeding after EC use and sexual intercourse that occurs
      shortly after taking EC pills. The language that writers use to express
      themselves reveals how users conceptualize their contraceptive and sexual health
      experiences. Many writers referred to sex with a hormonal contraceptive but not a
      barrier contraceptive as "unprotected sex," suggesting that patients may be using
      terms that do not mean what medical professionals might expect. E-mails sent to
      the site also demonstrate the importance of alternative resources that provide
      accurate medical information for patients who are unable to access health care or
      to discuss certain subjects with their providers.

PMID- 15964286
TI  - The acceptability of self-administration of subcutaneous Depo-Provera.
AB  - Depo-Provera (depot medroxyprogesterone acetate, or DMPA) is an important
      contraceptive option for women worldwide. Currently, it is only available in
      intramuscular form requiring regular quarterly routine attendance at a health
      facility. A new subcutaneous preparation has been developed. This is self
      administrable and could potentially reduce need for routine attendance to an
      annual visit. In a questionnaire survey of 176 women currently using DMPA, 67%
      would prefer to self-administer. Of the 33% who did not wish to self-administer,
      the most common reasons were a fear of needles (62%) and concern regarding
      incorrect administration (43%). In a second survey of 313 women not currently
      using DMPA, 64% of women said they would prefer to attend less often for
      contraceptive supplies. Twenty-six percent of women who had never used DMPA and
      40% of ex-users would seriously consider DMPA if self-administration were
      possible. Our findings would suggest that the advent of subcutaneous self
      administrable Depo-Provera with appropriate training and reminder system is
      likely to be beneficial and popular with many women.

PMID- 15964287
TI  - Prospective study on sexual behavior of women using 30 microg ethinylestradiol
      and 3 mg drospirenone oral contraceptive.
AB  - The aim of the study was to determine the changes, if any, on the sexual behavior
      of women using an oral contraceptive containing 30 microg ethinylestradiol (EE)
      and 3 mg drospirenone (DRSP). Eighty healthy volunteer women (age range, 19-31
      years), with regular menstrual cycle length (mean 27.6+/-3.1) and ovulation,
      participated in this prospective study. Sexual behavior was assessed using the
      self-administered Personal Experience Questionnaire, at baseline and at 3, 6 and
      9 cycles of pill use. Women reported increased (i) sexual enjoyment (p < .001),
      (ii) orgasm frequency (p < .05) and (iii) satisfaction with sexual activity (p <
      .05) during all periods of pill intake with respect to baseline. Both arousal and
      frequency of sexual activity improved at the sixth and ninth cycle of pill use (p
      < .05) with respect to baseline. Moreover, women reported decreased genital pain
      associated with intercourse during pill intake (p < .05). Desire did not change
      during the use of the pill (p = NS). The mild dose of EE may have improved
      vaginal lubrication, sexual arousal and decreased dyspareunia. Consequently,
      women may have experienced increased sexual performance. In addition, improved
      sexual activity could have been the result of the effects of DRSP, with its
      antimineralocorticoid effects which could improve pill compliance, with a more
      satisfied sexual life.

PMID- 15964288
TI  - Depo-Provera: use of a long-acting progestin injectable contraceptive in Turkish
      women.
AB  - OBJECTIVE: To assess the demographic and clinical characteristics and experience
      of Turkish women treated with depot medroxyprogesterone acetate (DMPA). STUDY
      DESIGN: This prospective clinical study was carried on 9262 subjects, treated
      with DMPA at Zekai Tahir Burak Women's Health Education and Research Hospital,
      Ankara, Turkey, between 1996 and 2004. RESULTS: The mean age of study population
      was 28.4+/-4.6 years; 1759 (19%) subjects were breast-feeding at the time of the
      first injection. Eight (0.08%) pregnancies occurred, within 3 months of injection
      in 9262 women. Of 9262 cases, irregular bleeding occurred in 80% (7410) of the
      women. Discontinuation rate with this contraceptive method was recorded as 71%
      (6576) of the subjects. The rate of other predominant side effects was observed
      as follows: 8% for increase in weight, 8% for breast engorgement, 7% for
      mastalgia, 5% for headache. CONCLUSION: The results of this study suggest that
      DMPA may be an attractive contraceptive choice for both the patient and the
      physician in some clinical situations, especially in women at risk for
      complications with oral hormonal contraceptives and women who have had low
      compliance with other contraceptive methods. Moreover, DMPA contraception might
      be particularly appropriate in some cases such as in the postpartum period and in
      lactating women.

PMID- 15964289
TI  - Comparison of gemeprost and vaginal misoprostol in first trimester mifepristone
      induced abortion.
AB  - BACKGROUND: The aim of this study was to compare efficacy and side effects of
      gemeprost and vaginal misoprostol in mifepristone-induced abortions in women up
      to 63 days of gestation. METHODS: A retrospective study of 833 consecutive
      patients admitted for medical termination of first trimester pregnancy was
      conducted. Four-hundred ten patients received mifepristone 600 mg, followed 48 h
      later by gemeprost 1 mg (regimen I), and 423 patients received mifepristone 200
      mg followed by vaginal misoprostol 800 microg (regimen II). Success rates were
      evaluated after 2 weeks and after 3 months. The severity of bleeding and side
      effects (pain, nausea, vomiting and diarrhea) was scored by the patients, and
      requests for supplementary analgesic treatment were recorded by the attending
      nurse. RESULTS: Success rates were 99% in both groups after 2 weeks of follow-up.
      At 3 months of follow-up, success rates had declined to 94% for regimen I and 96%
      for regimen II. The frequency of severe pain was higher in regimen I compared to
      regimen II (72% vs. 60%, p < .001), but the severity of bleeding and
      gastrointestinal side effects was similar in the two regimens. CONCLUSION: When
      combined with mifepristone, gemeprost and vaginal misoprostol are equally
      effective for termination of first trimester abortion, but may be associated with
      varying intensity of side effects.

PMID- 15964290
TI  - The effect of orally and vaginally administered misoprostol on inflammatory
      mediators and cervical ripening during early pregnancy.
AB  - OBJECTIVES: The objective of the present study was to investigate the effect of
      vaginally and orally administered misoprostol on the local cervical inflammatory
      response. METHODS: Healthy women with a normal intrauterine pregnancy between 8
      and 12 weeks of gestation presenting for an elective termination of pregnancy by
      vacuum aspiration were recruited into a cohort study with a control and a
      treatment group. In the treatment group, the women were randomized to
      misoprostol, 400 mug, given either orally or vaginally 3 h before surgery.
      Immunohistochemistry staining of CD45, CD68, MMP 8, MMP 9, TIMP 1 and TIMP 2 were
      assessed in cervical biopsies obtained directly prior to mechanical cervical
      dilatation and vacuum aspiration. RESULTS: In the treatment group, there was a
      greater amount of CD45-positive cells in the subepithelium region of the cervix
      compared to the control group. The staining of CD68 was similar in both groups.
      The immunostaining of MMP 8 and MMP 9 was greater in the treatment group, while
      the expression of TIMP 1 and TIMP 2 did not differ between control and treatment
      groups. CONCLUSIONS: Compared to untreated controls, treatment with misoprostol
      was associated with a greater expression of inflammatory cells. It could be
      hypothesized that administration of misoprostol mimics the cervical ripening at
      term pregnancy by a possible influx and activation of inflammatory cells, which
      increases MMP 8 and MMP 9 and thereby leads to the degradation of collagen and
      cervical softening.

PMID- 15964291
TI  - Serum Nestorone and ethinyl estradiol levels, and ovulation inhibition in women
      using three different dosage combinations of a Nestorone progestogen-ethinyl
      estradiol contraceptive vaginal ring on a bleeding-signaled regimen.
AB  - OBJECTIVES: This trial tested the hypothesis that menstrually signaled use of
      contraceptive vaginal rings ("rings") releasing low-dose combinations of
      Nestorone (NES) and ethinyl estradiol (EE) would reliably suppress luteal
      activity and ovulation, and prevent unintended pregnancy, while controlling the
      incidence of menstrual bleeding episodes and bleeding days. METHODS:
      Nestorone/ethinyl estradiol rings releasing 50/10, 50/20 and 150/15 mug/day were
      studied through 6 months. A ring was to be used continuously, until its removal
      was signaled by menstrual bleeding. Reinsertion was required 96 h after removal.
      Serum for NES, EE and progesterone were collected and assayed, and vaginal
      ultrasound scans were performed in three 5-week periods to examine luteal
      activity, follicular growth, ovulation and their correlates. In 10 subjects using
      the 150/15 ring, six samples were drawn in the 24-h period after ring removal to
      examine serum levels of NES and EE. RESULTS: One hundred sixty subjects at three
      doses provided blood samples. Median serum concentrations of NES and EE
      demonstrated dose ratios slightly below the nominal dose ratios expected. Serum
      NES concentrations declined 19-22% from weeks 3 to 25. Changes in EE levels
      depended on dose. Nestorone levels fell 81% by 24 h after ring removal and EE
      levels fell by 50%. Luteal activity was completely suppressed in 94-95% of cycles
      and in 90% of subjects. Three pregnancies occurred in subjects participating in
      this serum sampling study. CONCLUSION: Satisfactory serum levels of NES and EE,
      and a high level of ovulation suppression were achieved. Irregular ring use,
      however, permitted pregnancies to occur.

PMID- 15964292
TI  - Clinical performance and menstrual bleeding patterns with three dosage
      combinations of a Nestorone progestogen/ethinyl estradiol contraceptive vaginal
      ring used on a bleeding-signaled regimen.
AB  - OBJECTIVE: We examined the clinical performance of contraceptive vaginal rings
      (rings) delivering Nestorone (NES) progestin and ethinyl estradiol (EE). Ring
      removal times were signaled by menstrual events. Bleeding patterns, adverse
      events, patterns of use and continuation rates were the principal parameters
      evaluated. METHODS: In a two-stage 6-month trial, subjects were randomized to use
      rings releasing 50 microg/day of NES and either 10 (50/10) or 20 (50/20)
      microg/day of EE. Subjects were to keep rings continuously in situ until
      menstrual bleeding or prolonged spotting-signaled removal. Reinsertion was to
      occur 96 h later. After the randomized stage, an open-label 6-month trial of
      rings releasing 150 microg/day of NES and 15 microg/day of EE (150/15) began with
      the same menstrually signaled regimen. RESULTS: Two-hundred forty-six subjects
      participated in the trial. Six-month pregnancy rates ranged by ring dose from 1.3
      to 3.9 per 100. For each ring dose combination, 6-month continuation rates were
      above 80 per 100. Bleeding and spotting (B+S) days in women with the 50
      microg/day NES rings were similar in number to those experienced by cycling women
      not using contraception. Nevertheless, in the initial 90 days, fewer B+S days
      were reported by subjects with the 50/20 ring than by subjects with the 50/10
      ring (p < .05). Throughout the trial, subjects using the 150/15 ring reported
      significantly fewer B+S episodes than did subjects with either 50 microg/day NES
      ring. CONCLUSION: Combined contraceptive rings used with a bleeding-signaled
      regimen led to few terminations attributed to bleeding problems and to acceptable
      continuation rates. The 150/15 ring appeared to induce fewer bleeding problems
      than did the lower-dose NES combination rings, but no important difference in 6
      month continuation rates among the three doses was noted.

PMID- 15964293
TI  - Lea's Shield: colposcopic and microbiological testing during 8 weeks of use.
AB  - OBJECTIVES: The aims of this study were to assess the effects of Lea's Shield(R)
      plus nonoxynol-9 spermicide on signs and symptoms of female genital irritation
      and cervical and vaginal microflora during 8 weeks of use with intercourse and to
      analyze problems associated with the use of the device. METHODS: In this open
      label, single-arm study, participants were evaluated by pelvic examination,
      colposcopy and vaginal and cervical cultures. RESULTS: About 13% of women (4/30)
      reported symptoms of irritation, and minor product-related colposcopic findings
      were seen in about one third (11/30). Although average colony counts for
      enterococcus, Escherichia coli and anaerobic gram-negative rods increased during
      product use, no clinical diagnoses of infection were made. Most users reported at
      least one problem using Lea's Shield. CONCLUSION: Lea's Shield, when used for 8
      weeks during intercourse, is associated with evidence of genital irritation in a
      minority of users and with changes in vaginal microflora that do not appear to
      correlate with clinical infections.

PMID- 15964294
TI  - Vaginal speculum lubrication and its effects on cervical cytology and
      microbiology.
AB  - The prevailing approach to Papanicolaou (Pap) and endocervical Gen-Probe(R)
      screening is to use an unlubricated vaginal speculum because of concerns that gel
      lubricant interferes with Pap smear adequacy and cervical microbiology. This
      study tests the hypothesis that lubrication of metal specula with a
      bacteriostatic gel does not increase unsatisfactory cervical cytology or decrease
      detection rates of endocervical Chlamydia trachomatis or Neisseria gonorrhoeae.
      At a publicly funded family planning clinic site, each of eight consecutive
      months was randomly designated by computer as an exclusively gel-lubricated or
      water-moistened specula use month. The assigned vaginal speculum intervention was
      used on all patients receiving a Pap smear and/or combination DNA probe assay for
      endocervical C. trachomatis and N. gonorrhoeae. From July 2003 through February
      2004, 3460 Pap smears and 5535 combination probe assays for C. trachomatis and N.
      gonorrhoeae were collected from 6538 patients. During the 4 months of gel
      lubricant use, the rate of unsatisfactory cytology was 1.1% compared to 1.5%
      during the 4 months of water lubrication [odds ratio (OR) 0.74; 95% confidence
      interval (CI) 0.41-1.35]. During the 4 months of gel lubricant use, the detection
      rate for endocervical C. trachomatis was 1.5% compared to 1.5% (OR 1.05; 95% CI
      0.67-1.62) in water lubricant months. The study population N. gonorrhoeae
      infection rate was too low to statistically analyze. The use of a small amount of
      gel lubricant on metal vaginal specula did not increase unsatisfactory cytology
      or decrease endocervical C. trachomatis detection rates when compared to water
      lubricant.

PMID- 15964295
TI  - Vaginal distribution of two volumes of the novel microbicide gel cellulose
      sulfate (2.5 and 3.5 mL).
AB  - This was a blinded crossover study to determine the in vivo distribution of 2.5
      and 3.5 mL of 6% cellulose sulfate gel. This potential vaginal microbicide was
      mixed with dilute gadolinium chelate and inserted into the vagina. Magnetic
      resonance imaging was performed at baseline and repeated after 5, 20, 35 and 50
      min with subjects either resting or ambulating between data acquisitions. Use of
      2.5 mL with no ambulation gave low linear spread (53.1% of vaginal length) and
      surface contact (61.7%) at 50 min. Using 3.5 mL of gel with ambulation improved
      linear spread (84.5%) and surface contact (85.9%) of the gel in the same time
      interval without significant leakage. Most linear spreading took place in the
      first 5 min after insertion, although lateral spreading continued to increase
      with time especially when ambulation took place. Leakage and gel was not a
      significant problem at either volume.

PMID- 15964296
TI  - In vitro effect of levonorgestrel on sperm fertilizing capacity and mouse embryo
      development.
AB  - The objectives of this study were to assess the expression of alpha-d-mannose
      binding sites in human spermatozoa, human sperm-oocyte interaction and the
      development of early stages of mouse embryo in the presence of levonorgestrel
      (LNG). Semen samples were obtained from 16 normozoospermic men. Spermatozoa were
      separated by Percoll gradient and incubated overnight for capacitation. The
      kinetic analysis of the expression of alpha-D-mannose binding sites was
      determined at 0, 4 and 22 h and in 22 h-capacitated spermatozoa that had been
      exposed to 1, 10 or 100 ng/mL of LNG or to a control medium for 30 min. Sperm
      binding sites for alpha-D-mannose were detected using commercial alpha-D
      mannosylated bovine serum albumin conjugated with fluorescein isothiocyanate. To
      evaluate sperm-oocyte interaction, each oocyte was placed in a 100-microL droplet
      containing one of the three doses of LNG or control medium and inseminated with
      1.0 x 10(5) motile spermatozoa/mL, after which the number of bound spermatozoa
      was evaluated. A total of 157 two-cell embryos recovered from eight mice was
      pooled and assigned randomly to treatment (1, 10 or 100 ng/mL of LNG) or control
      groups. There was a significant increase in the expression of specific alpha-d
      mannose binding sites (Patterns II and III) during the incubation of spermatozoa
      under capacitating conditions. In the presence of LNG, results showed that there
      was no significant difference in the expression of specific alpha-d-mannose
      binding sites (Patterns II and III) at any LNG concentration tested compared with
      those spermatozoa in control medium. None of the LNG concentrations were capable
      of modifying the number of spermatozoa tightly bound to the human zona pellucida.
      There was no association between the presence or absence of LNG or the different
      doses of LNG evaluated and mouse embryo development. In conclusion, the
      hypothesis that in vitro exposure to LNG could interfere with sperm function and
      could contribute to the mechanism of action of this form of contraception was not
      confirmed but cannot be ruled out by the results of this study.

PMID- 15964298
TI  - Cervical priming with misoprostol.

PMID- 15964297
TI  - Histological assessment of ovaries and uterus of rats subjected to nandrolone
      decanoate treatment.
AB  - This study aimed to analyze the effects of nandrolone decanoate on the ovaries
      and uterus of adult females rats. This drug was administered intraperitoneally,
      at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight,
      respectively, in the first, second and third week of treatment. The females of
      the control group received a physiological solution. The rats treated with
      nandrolone decanoate showed estral acyclicity and there was destruction of
      follicular units and an absence of corpus luteum in the ovaries. In the uterus,
      the drug promoted morphological alterations, characterized by vacuolated
      epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights
      were not affected by the steroid treatment. Nandrolone decanoate affects the
      sexual cycle and promotes histological alterations in the ovaries and uterus of
      adult female rats.

PMID- 15964300
TI  - Risk factors for post-operative mortality in bariatric surgery.
AB  - BACKGROUND: Appropriate patient selection is crucial to the success of bariatric
      surgery (BaS). The objective of this study was to identify risk factors for
      increased post-operative mortality in patients undergoing BaS using a nationally
      representative sample. MATERIALS AND METHODS: BaS patients > or = 18 years old in
      the United States were identified from the 2001 Nationwide Inpatient Sample
      (NIS). The effect of gender, age, insurance status, and need for re-operation on
      post-operative mortality was examined using a multivariate logistic regression
      model. RESULTS: A national cohort of 54,878 patients was identified with age 41
      +/- 0.2 years (mean +/- SE), 84% women, length of stay (LOS) 3.9 +/- 0.2 days,
      and overall mortality of 4 per 1,000 BaS patients. Mean LOS of those who died was
      17.6 +/- 3.7 days. Adjusting for comorbidities and demographics, men had
      increased likelihood of death [odds ratio (OR) 2.1, 95% confidence interval (CI)
      1.1-4.3, P < 0.05]. Compared to younger patients, those aged above 39 years had
      over two-fold risk of death [ages 40-49: OR 2.6, 95% CI 1.1-6.5, P < 0.05; ages
      50-59: OR 4.3, 95% CI 1.7-11, P < 0.05]. Medicaid patients [OR 4.7, 95% CI 1.2
      13, P < 0.05 compared to privately insured] and those requiring re-operation [OR
      22, 95% CI 5.4-88, P < 0.05] had higher odds of dying. CONCLUSION: Based on
      national data, risk factors for increased post-operative mortality in BaS
      patients include male gender, age > 39 years, Medicaid insured, and need for re
      operation. These data can assist in optimizing BaS patient outcomes.

PMID- 15964301
TI  - Screening methods for high-grade dysplasia in patients with anal condyloma.
AB  - Human papilloma virus (HPV) is one of the most common sexually transmitted
      diseases in the United States. HPV infection can cause anal condylomas and is a
      risk factor for dysplasia. High-grade dysplasia may progress to squamous cell
      carcinoma. Currently, biopsy and histological examination are required to grade
      dysplasia. The purpose of this study is to determine whether anal cytology,
      morphological characteristics, and/or the presence of high-risk oncogenic HPV
      types are effective noninvasive methods to detect high-risk anal condylomas.
      PATIENTS AND METHODS: From November 2003 to June 2004, all patients with anal
      condyloma were prospectively evaluated for anal cytology, high-risk oncogenic HPV
      types, and tissue biopsies. The Bethesda classification system was used to
      classify cytologic findings and histological examination, which were grouped as
      high-risk (HRL) and low-risk (LRL) lesions. Histology results served as true
      disease for all comparisons. RESULTS: Forty-seven patients with anal condyloma
      were studied; 43 (91.5%) were men, and the mean age was 39 +/- 11 years.
      Histology showed 19 (40.5%) patients with HRL, and 28 (59.5%) patients with LRL.
      Cytology correctly identified 8 patients with HRL and 27 patients with LRL
      (sensitivity 42% and specificity 96%). High-risk oncogenic HPV-types were found
      in 84.2% of HRL and 39.3% of LRL (P = 0.0029). Combining cytology with oncogenic
      HPV-testing, the sensitivity of detecting HRL increased to 89%, and specificity
      decreased to 42%. CONCLUSION: Anal cytology alone is not accurate for detecting
      HRL in patients with anal condylomas. Combining oncogenic HPV-testing with
      cytology is more sensitive in detecting HRL in patients with anal condyloma, and
      therefore, a more effective screening tool.

PMID- 15964302
TI  - Effects of cyclophilin A on myeloblastic cell line KG-1 derived dendritic like
      cells (DLC) through p38 MAP kinase activation.
AB  - BACKGROUND: Cyclophilin A (CypA) is a ubiquitously distributed intracellular
      protein as well as a secreted protein and has recently been reported to be an
      immunomodulatory molecule. The objective of this study was to determine the
      effect of CypA on dendritic cell (DC) differentiation, activation, and functional
      maturation. The role of p38 MAP kinase in DC functions was also investigated.
      MATERIALS AND METHODS: KG1 cells (CD34+ human myeloblastic cell line) were
      treated with cytokines (GM-CSF+IL-4) and/or CypA and expression of cell surface
      markers was analyzed by FACS analysis. The antigen-uptake capacity of different
      DCs was determined by FITC-dextran uptake assay. Antigen-presentation capacity of
      DCs was determined by allogeneic mixed lymphocyte reaction (MLR) by [3H]
      thymidine incorporation assay. To assess the T cell polarization stimulated by
      KG1 derived DCs, various Th1 and Th2 cytokines secreted by allostimulated CD4+
      and CD8+ T cells were determined by Bioplex cytokine assay. Total and
      phosphorylated p38 MAPK activity in CypA treated DCs was detected by Bioplex p38
      total and phosphoprotein assay. RESULTS: During the differentiation of KG1 cells
      to immature DCs, cell surface expression of CD11b was increased by 30.6% for CypA
      alone, 55% for CypA plus cytokines, and 44% for cytokines alone. Similarly, CypA
      alone increased the cell surface expression of CD11c by 59% as compared to CypA
      plus cytokines (68%) and cytokines alone (50%). CypA up-regulated the antigen
      uptake capacity of the immature DCs to a greater extent (5 times) as compared to
      cytokines alone (2.5 times). Moreover, CypA augmented the capacity of DCs to
      present antigens to allogenic CD8+ T cells, and also increased the secretion of
      Th1 type cytokines TNF-alpha and IFN-gamma from the allogenic CD4+ T cells.
      Furthermore, CypA induced the phosphorylation and hence activation of MAP kinase
      p38. Pre-treatment with SB-203580, a p38 inhibitor, significantly reduced MLR
      stimulatory capacity of CypA-induced DCs in both CD8+ and CD4+ T cells (P <
      0.05). CONCLUSIONS: CypA enhances DC differentiation and maturation by up
      regulating CD11b and CD11c expression. CypA can also augment DC antigen uptake
      and antigen presentation, which may be mediated by the p38 signaling pathway.

PMID- 15964303
TI  - Urokinase-induced smooth muscle cell migration requires PI3-K and Akt activation.
AB  - OBJECTIVE: To examine the role of the phospho-inositol-3'-kinase (PI3-K)-akt
      signaling axis during smooth muscle cell (SMC) migration in response to the
      aminoterminal fragment of urokinase (ATF). BACKGROUND: Urokinase (uPA) is
      involved in vessel remodeling and mediates smooth muscle cell migration.
      Migration in response to urokinase is dependent on ATF. The role of PI3-K/akt
      signaling during migration in response to the uPA fragments is not understood.
      METHODS: Murine arterial SMCs were cultured in vitro. Linear wound and Boyden
      microchemotaxis assays of migration were performed in the presence of ATF with
      and without the PI3-K inhibitors (Wortmannin, Wn [10 nm] and LY294002, LY [10
      microm]) and an akt inhibitor (aktI, [10 microm]). Western blotting was performed
      for akt, ERK1/2, and GSK3beta phosphorylation after cells were stimulated with
      ATF in the presence and absence of the inhibitors. Statistics were analyzed by
      one-way ANOVA. RESULTS: Both PI3-K and akt inhibitors blocked the migratory
      response to ATF in both assays. ATF induced time-dependent increases in akt
      phosphorylation at both S472 and T308 sites and ERK1/2 phosphorylation.
      Activation of akt and ERK1/2 was inhibited by Wn and LY. Manumycin A, a ras
      inhibitor, did not inhibit activation of akt but did inhibit ERK1/2 activation.
      Activation of akt and the dephosphorylation of its downstream kinase GSK3beta
      were inhibited by the akt inhibitor. Direct inhibition of akt did not influence
      ERK1/2 activation and inhibition of ERK1/2 did not influence akt activation.
      CONCLUSION: ATF mediated migration is PI3-K dependent and activates two separate
      pathways: ERK1/2 and akt. ATF induces akt phosphorylation through a PI3K-mediated
      but ras-independent mechanism while both ras and PI3K are required for ERK1/2
      activation. Defining key signaling pathways is vital to regulate vessel
      remodeling.

PMID- 15964304
TI  - MAPK and PI3K inhibition reduces proliferation of Barrett's adenocarcinoma in
      vitro.
AB  - BACKGROUND: Esophageal adenocarcinoma often arises from Barrett's esophagus.
      Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)
      play critical roles in cell survival. We hypothesized that inhibition of these
      pathways in Barrett's adenocarcinoma would decrease cell proliferation and alter
      apoptosis in vitro. MATERIALS AND METHODS: Two Barrett's-associated
      adenocarcinoma cell lines, SEG-1 (wild-type p53) and BIC-1 (mutant p53), were
      treated with MAPK (U0126) and PI3K (LY294002) inhibitors at 20 microm
      concentrations. After 24 and 72 h, cell viability was measured by MTT assay.
      Apoptosis and necrosis were evaluated by the Annexin V-FITC assay. Statistical
      analysis was performed by ANOVA. RESULTS: LY294002 and U0126 treatment produced
      significant reductions (range 15.7 to 62.0%, P < 0.05) in cellular proliferation
      at both 24 and 72 h in the SEG-1 cells. BIC-1 cell viability was reduced (39.3 to
      56.4%, P < 0.05) at 72 h. Both early and late apoptotic activity were
      significantly increased (P < 0.05) in the SEG-1 cells using both inhibitors.
      Necrosis was significantly reduced (P < 0.05) using both inhibitors. No changes
      in either early or late apoptosis or necrosis were observed in the BIC-1 cells.
      CONCLUSIONS: Herein, we report significant antiproliferative effects against
      Barrett's adenocarcinoma by MAPK and PI3K inhibition in vitro. Pro-apoptotic
      mechanisms prevail in the wild-type p53 cells. Further investigation is warranted
      to advance the clinical treatment of this devastating disease.

PMID- 15964305
TI  - Changing trends for surgery in elderly patients with hyperparathyroidism at a
      single institution.
AB  - BACKGROUND: Many elderly patients with primary hyperparathyroidism (1HPT), which
      increases in incidence with age and is frequently asymptomatic, are often not
      referred for surgery. However, the development of minimally invasive techniques
      has facilitated complex operations even in the elderly. Therefore, we sought to
      delineate the changes in the trends for surgical referral at our institution for
      patients over 70 years of age with 1HPT. METHODS: From January 1990 to March
      2004, 422 patients underwent surgery for 1HPT at our institution. Of these, 98
      were 70 years or older. In 2001, we introduced minimally invasive radioguided
      parathyroidectomy (MIRP). Patients were then analyzed based upon the availability
      of this technology (pre-MIRP era 1990-2000, and MIRP era 2001-2004). RESULTS: In
      the MIRP era, more elderly patients were referred for surgery when compared to
      the pre-MIRP era (30% versus 18%, P = 0.001). On average, 18 elderly
      patients/year had parathyroid surgery in the MIRP era compared to only 4 elderly
      patients/year pre-MIRP, representing a 4.5-fold increase. Furthermore, there were
      significantly more patients undergoing parathyroidectomy who were asymptomatic
      from 1HPT during the MIRP era (14% versus 2%, P < 0.001). Importantly, patients
      who underwent surgery in the MIRP era had a higher cure rate, lower complication
      rate, and shorter hospital stay. CONCLUSIONS: Since the introduction of MIRP at
      our institution, there has been an increase in the number of elderly patients
      with 1HPT referred for surgery as well as the proportion with only mild disease.
      Furthermore, there have been improvements in elderly patient outcomes during this
      time. MIRP is one of several factors that have led to an increase in elderly
      patients undergoing surgery for 1HPT.

PMID- 15964306
TI  - Antiatherosclerotic effects of dietary supplementations of garlic and turmeric:
      Restoration of endothelial function in rats.
AB  - Protections of endothelial integrity by elimination of certain risk have proven
      to be effective in maintaining hemostasis and in slowing the progress of the
      cardiovascular disease. Indigenous drugs are the natural source of protection
      against these disorders, which can be used more effectively by the knowledge of
      their active ingredients as well as by their mechanism of action. Most prominent
      among these drugs are garlic, [Alium sativum L., Family: Liliaceae, Bulbs] and
      turmeric [Curcuma longa L., Family: Zingiberaceae, Rhizomes]; commonly used
      Indian traditional spices. In the present study, we examined the
      atheroscleroprotective potential of diet supplementation of garlic and turmeric
      by measuring serum lipid profile, changes in cardiovascular parameters i.e.
      arterial blood pressure, electrocardiogram and heart rate. We further tried to
      elucidate the mechanism of restoration of endothelial function and the role of
      endothelium-derived factors mainly, nitric oxide (NO) and cycloxygenase derived
      contracting factors. A notable restoration of arterial blood pressure was seen in
      animals on garlic and turmeric supplemented diet. Animals on supplemented diet
      showed a significantly enhanced vasorelaxant response to adenosine,
      acetylcholine, isoproterenol and contractile effect of 5-hyderoxytryptamine was
      significantly attenuated. Inhibition of these responses by L-NMMA was smaller in
      tissues from herbal treated animals. Incubation of tissues with L-arginine (10(
      5) M) resulted in a significant reversal of L-NMMA induced inhibition of
      endothelium-mediated relaxation, which appeared to be pronounced in rings from
      animals supplemented with herbs as compared to hypercholesterolemic animals.
      Addition of indomethacin (10(-5) M) augmented the relaxation in all the groups of
      animals. The present study demonstrated that garlic and turmeric are potent
      vasorelaxants as well as reduce the atherogenic properties of cholesterol.
      Whether combination of these vasodilators in cardiovascular disorders with
      increased peripheral vascular resistance remains to be determined.

PMID- 15964307
TI  - Protective effects of intracellular reactive oxygen species generated by 6
      formylpterin on tumor necrosis factor-alpha-induced apoptotic cell injury in
      cultured rat hepatocytes.
AB  - The effects of 6-formylpterin on tumor necrosis factor (TNF)-alpha-induced
      apoptotic cell injury were studied in cultured rat hepatocytes. The incubation of
      the hepatocytes with TNF-alpha and actinomycin D (ActD) induced the apoptotic
      cell injury. The level of aspartate transaminase (AST) in the culture supernatant
      increased, and the cell viability, estimated by mitochondrial respiration (MTT
      assay), decreased. The DNA fragmentation and the caspase 3-like activity, which
      are characterized to apoptosis, increased. When the hepatocytes were incubated
      with 100-500 microM 6-formylpterin, the intracellular formation of reactive
      oxygen species (ROS) was observed, and the ratio of reduced and oxidized
      glutathione (GSH/GSSG) of whole cell lysate decreased. The co-incubation of the
      TNF-alpha/ActD-treated hepatocytes with 100-500 microM 6-formylpterin attenuated
      the TNF-alpha/ActD-induced apoptotic cell injury. The level of AST decreased and
      the cell viability increased. Both the DNA fragmentation and the caspase 3-like
      activity decreased. The caspases, executors of apoptosis, are known to require a
      reduced cystein in their active site to function, and the intact intracellular
      GSH/GSSG is essential for the caspase activation. Therefore, our findings suggest
      that intracellular ROS generated by 6-formylpterin decline the intracellular
      redox state to an oxidant state, which suppresses the caspase activity and
      prevents the apoptotic cell injury of hepatocytes.

PMID- 15964308
TI  - The inhibitory effect of a Korean herbal medicine, Zedoariae rhizoma, on growth
      of cultured human hepatic myofibroblast cells.
AB  - The aim of this study was to assess the effect of ZR on the growth of cultured
      human hepatic myofibroblast cells (hMF). The zedoary (Zedoariae Rhizoma) made
      from the dried rhizome of Curcuma zedoaria Roscoe is an herbal drug used as an
      aromatic stomachic. The plant is a perennial herb which is natively distributed
      throughout Korea and is a traditional Korean herbal medicine. Zedoariae rhizoma
      is a bioactive traditional medicine with anti-tumor, anti-atherosclerosis, anti
      inflammation, and growth-regulating properties. During the course of liver
      fibrogenesis, hMF, mostly derived from hepatic stellate cells, proliferate and
      synthesize excessive amounts of extracellular matrix components. To evaluate the
      antiproliferative effect of a traditional herbal medicine, Zedoariae rhizoma
      water extracts (ZR) was examined on the growth inhibition of hMF since
      proliferation of hMF is known to be central for the development of fibrosis
      during liver injury, and factors that may limit their growth are potential
      antifibrotic agents. The aim of this study was to test the effects of ZR on the
      proliferation in cultured hMF. hMF were obtained by outgrowth from human liver
      explants. ZR markedly reduced serum driven cell proliferation, as assessed by
      nuclear autoradiography experiments and measurement of actual cell growth. Growth
      inhibition was totally reversed after removal of the ZR. ZR potently inhibited
      hMF growth (IC50 = 8.5 microg/ml), in a pertussis toxin-insensitive manner.
      Analysis of the mechanisms involved in growth inhibition revealed that ZR rapidly
      increased prostaglandin E2 production and in turn cAMP, which inhibited hMF
      proliferation, did not affect cAMP levels. Production of cAMP by ZR was abolished
      by NS-398, a selective inhibitor of cycloxygenase (COX)-2. Also, ZR potently
      induced COX-2 protein expression. Blocking COX-2 by NS-398 blunted the
      antiproliferative effect of ZR. We conclude that ZR inhibits proliferation of
      hMF, probably via an intracellular mechanism, through early COX-2-dependent
      release of prostaglandin E2 and cAMP, and delayed COX-2 induction. Our results
      indicated a novel role for ZR as a growth inhibitory mediator and pointed out its
      potential involvement in the negative regulation of liver fibrogenesis. The
      results that ZR exhibits potent antiproliferative and antifibrogenic effects
      toward hMF, indicated that ZR might have therapeutic implications in chronic
      liver disease.

PMID- 15964309
TI  - Effect of crocin on experimental atherosclerosis in quails and its mechanisms.
AB  - In the present study, we examined the prophylaxis effect of crocin on
      experimental atherosclerosis and its possible mechanisms. The atherosclerosis
      formation was induced by hyperlipidamic diet in quails. At the 9th week, serum
      lipid, MDA and NO were measured, and HE staining was used to investigate the
      histopathological changes of aorta. Bovine aortic endothelial cells (EC) were
      obtained from the thoracic aorta of newborn calves. After incubation of the cells
      with Ox-LDL (50 mg x L(-1)) for 24 h, the activities of LDH, NO in culture media
      and activity of NOS in endothelial cells were measured, flow cytometer was used
      to determine the rate of endothelial cells apoptosis. Peritoneal macrophages were
      obtained from thioglycolate-injected mice. Cholesterol and free cholesterol in
      cells were assayed after incubation of the cells with Ox-LDL. Bovine aortic
      smooth muscle cells (SMC) were obtained from the thoracic aorta of newborn calf.
      Proliferation was induced by 100 microg x L(-1) Ox-LDL and antiproliferative
      effect of crocin on SMCs were observed. SMCs cycle phases were measured by flow
      cytometry. SMCs were loaded with Fluo-3/AM and [Ca2+]i was measured by Laser
      Scanning Confocal Microscope (LSCM). Crocin could reduce the level of serum TC,
      TG, LDL-C and inhibit the formation of aortic plaque. Crocin could reduce MDA and
      inhibit the descending of NO in serum. Compared with control, Ox-LDL group could
      increase the activity of LDH and decrease activity of NO in culture media and
      activity of NOS in endothelial cells, preincubated with crocin, the effects of Ox
      LDL were inhibited. Crocin could decrease the EC apoptosis induced by Ox-LDL.
      Crocin concentration-dependently inhibited the TC and CE elevation induced by Ox
      LDL in macrophages. Crocin could inhibit the proliferation of SMCs induced by Ox
      LDL. In the presence or absence of extracellular Ca2+, crocin concentration
      dependently inhibited the [Ca2+]i elevation induced by 120 mg x L(-1)Ox-LDL, In
      the absence of extracellular Ca2+, crocin could inhibit the [Ca2+]i elevation
      induced by CHCl3 in a concentration-dependent manner. The results indicated that
      crocin could inhibit the formation of atherosclerosis in quails. Crocin had
      protective effects on endothelial cells. Crocin could decrease CE in macrophages
      and uptake of Ox-LDL, inhibiting the formation of foam cell, which would promote
      the initiation and progression of atherosclerosis. Crocin could inhibit the
      [Ca2+]i elevation in smooth muscle cell, Ca2+ is an important second messenger
      that regulates a variety of cellular processes, including smooth muscle cell
      proliferation and gene expression . Crocin exerted antiatherosclerotic effects
      through decreasing the level of Ox-LDL that plays an important role in the
      initiation and progression of atherosclerosis.

PMID- 15964310
TI  - Orally administrated rare earth element cerium induces metallothionein synthesis
      and increases glutathione in the mouse liver.
AB  - The influence of oral administration of rare earth element cerium (Ce) was
      studied in relation to metallothionein (MT) and glutathione (GSH) content in the
      organs of ICR mice, which were administered heavy metal cadmium (Cd) for
      comparison. Male ICR mice were divided into 9 groups: 1 control group, 4 cerium
      groups and 4 cadmium groups, each with 4 mice, for a total of 36 mice. Ce groups
      included a 20 ppm CeCl3 diet (Ce-low) group and a 200 ppm CeCl3 diet (Ce-high)
      group, as did Cd groups, i.e., a 20 ppm CdCl2 diet (Cd-low) group and a 200 ppm
      CdCl2 diet (Cd-high) group. Each group was subdivided in 2 groups except a
      control group: 6-week administration group and 12-week administration group. The
      level of plasma aspartate aminotransferase(AST) activity, plasma alanine
      aminotransferase(ALT) activity, plasma cholesterol and plasma triglyceride in the
      Ce-low, Cd-low, Ce-high, and Cd-high group were higher than that of control
      group, although there were no significant differences (p > 0.05). By contrast,
      both Ce and Cd groups had higher levels of MT and GSH in hepatic cells compared
      to the control group (p < 0.05) and decreased liver tissue level of lipoperoxide
      (p < 0.05). These groups also had decreased plasma superoxide dismutase (SOD)
      activity (p < 0.05), and increased plasma level of lipoperoxide (p > 0.05). In
      conclusion, it is suggested that orally administered Ce increases MT and GSH as
      an antioxidant in the mouse liver, and these reaction are probably caused by
      increases in the oxidative stress with Ce.

PMID- 15964311
TI  - Cinnamaldehyde-induced apoptosis in human PLC/PRF/5 cells through activation of
      the proapoptotic Bcl-2 family proteins and MAPK pathway.
AB  - Cinnamaldehyde (Cin) has been shown to be effective in inducing apoptotic cell
      death in a number of human cancer cells. However, the intracellular death
      signaling mechanisms by which Cin inhibits tumor cell growth are poorly
      understood. In this study, we investigated the effect of mitogen-activated
      protein kinases (MAPKs) inhibitors [namely SP600125 (a specific JNK inhibitor),
      SB203580 (a specific p38 inhibitor) and PD98059 (a specific ERK inhibitor)] on
      the stress-responsive MAPK pathway induced by Cin in PLC/PRF/5 cells. Trypan blue
      staining assay indicated that Cin was cytotoxic to PLC/PRF/5 cells. Cin caused
      cell cycle perturbation (S-phase arrest) and triggered apoptosis as revealed by
      the externalization of annexin V-targeted phosphatidylserine and accumulation of
      sub-G1 peak. It down-regulated the Bcl-2 and Mcl-1 expression, and up-regulated
      Bax protein in a time-response manner. Treatment with 1 microM Cin resulted in an
      activation of caspase-8 and cleavage of Bid to its truncated form in a time
      dependent pattern. JNK, ERK and p38 kinases in cells were activated and
      phosphorylated after Cin treatment. Pre-incubation with SP600125 and SB203580
      markedly suppressed the effect of Cin-induced apoptosis, but not PD98059. Both
      SP600125 and SB203580 significantly prevented the phosphorylation of JNK and p38
      proteins, but not ERK. These results conclude that Cin triggers apoptosis in
      PLC/PRF/5 cells could be through the activation of pro-apoptotic Bcl-2 family
      (Bax and Bid) proteins and MAPK signaling pathway.

PMID- 15964312
TI  - PDGF activates K-Cl cotransport through phosphoinositide 3-kinase and protein
      phosphatase-1 in primary cultures of vascular smooth muscle cells.
AB  - K-Cl cotransport (K-Cl COT, KCC) is an electroneutrally coupled movement of K and
      Cl present in most cells. In this work, we studied the pathways of regulation of
      K-Cl COT by platelet-derived growth factor (PDGF) in primary cultures of vascular
      smooth muscle cells (VSMCs). Wortmannin and LY 294002 blocked the PDGF-induced K
      Cl COT activation, indicating that the phosphoinositide 3-kinase (PI 3-K) pathway
      is involved. However, PD 98059 had no effect on K-Cl COT activation by PDGF,
      suggesting that the mitogen-activated protein kinase pathway is not involved
      under the experimental conditions tested. Involvement of phosphatases was also
      examined. Sodium orthovanadate, cyclosporin A and okadaic acid had no effect on
      PDGF-stimulated K-Cl COT. Calyculin A blocked the PDGF-stimulated K-Cl COT by
      60%, suggesting that protein phosphatase-1 (PP-1) is a mediator in the PDGF
      signaling pathway/s. In conclusion, our results indicate that the PDGF-mediated
      pathways of K-Cl COT regulation involve the signaling molecules PI 3-K and PP-1.

PMID- 15964313
TI  - Dysfunction of myocardial sarcoplasmic reticulum in rats with myocardial
      calcification.
AB  - We investigated the relationship between cardiac dysfunction and Ca2+ transport
      in the myocardial sarcoplasmic reticulum (SR) during the pathogenesis of
      cardiovascular calcification in rats. The possible mechanism of SR dysfunction
      was explored by detecting the alteration of the nitric oxide/nitric oxide
      synthase (NO/NOS) pathway in the SR. Using the vitamin D plus nicotine (VDN
      treatment for 2 week and 6 week) experimental model of cardiac calcification,
      cardiac function and sarcoplasmic reticulum function were measured. Inhibition of
      cardiac functions in vivo (peak rate of contraction and peak rate of relaxation,
      P < 0.05 or P < 0.01) were observed in all calcification groups, simultaneously,
      Ca2+ release and uptake in the SR as well as the Ca2+ release channel and Ca2+
      pump activity were inhibited. Myocardial Ca2+ concentration and cardiac and SR
      dysfunction were inversely related (P < 0.05). The specific NO/NOS pathway (NO
      production, NOS activity and nNOS expression in the SR) was upregulated in the SR
      and associated with calcification (both 2- and 6 week VDN groups). These results
      indicate that cardiac dysfunction associated with myocardial calcification might
      be mediated by SR dysfunction, which may result from an impaired SR-specific
      NO/NOS pathway.

PMID- 15964314
TI  - Potential hypoglycemic effects of Chlorella in streptozotocin-induced diabetic
      mice.
AB  - Chlorella, a type of unicellular fresh water algae, has been a popular foodstuff
      in Japan and Taiwan. Chlorella has been shown to produce hypoglycemic effects in
      alloxan-induced diabetic animals. However, there are no other reports of the
      effects of this substance in other diabetic animal models. Here we have used
      streptozocin (STZ)-induced diabetic mice to study the thypoglycemic effects of
      Chlorella. Diabetes was induced in ICR strain mice by the i.p. injection of STZ.
      Vehicle-treated ICR mice were used as normal control animals and glibenclamide
      was used as a positive drug control. The effects of Chlorella on basal blood
      glucose, exogenous insulin sensitivity test and plasma insulin levels were
      measured. In normal mice Chlorella produced a transient hypoglycemic effect at 90
      min after acute administration; whereas glibenclamide produced a more sustained
      hypoglycemic effect between 90 min and 180 min after acute administration.
      Chlorella did not affect the basal blood glucose level in STZ mice. However,
      Chlorella enhanced and prolonged the hypoglycemic effects of injected insulin in
      STZ mice for a further 60 min compared to the normal vehicle-treated group.
      Plasma insulin levels were increased in normal mice after treatment with
      glibenclamide, whereas Chlorella had no such effect. The current results indicate
      that Chlorella enhances the hypoglycemic effects of exogenous insulin at a dose
      which does not produce hypoglycemia in STZ mice, suggesting that insulin
      sensitivity is increased in these mice.

PMID- 15964315
TI  - Molecular dissection of a medicinal herb with anti-tumor activity by
      oligonucleotide microarray.
AB  - It is difficult to understand precisely the physiological actions of herbs
      because they contain a complex array of constituent molecules. In the present
      study we used DNA microarray data for 12600 genes to examine the anti
      proliferative activity of the herb Coptidis rhizoma and eight constituent
      molecules against eight human pancreatic cancer cell lines. We identified 27
      genes showing strong correlation with the 50% inhibitory dose (ID50) of C.
      rhizoma after 72-h exposure. Hierarchical cluster analysis with correlation
      coefficients between expression levels of these 27 C. rhizoma-related genes and
      the ID50 of each constituent molecule classified these test molecules into two
      clusters, one consisting of C. rhizoma and berberine and the other consisting of
      the remaining seven molecules. Our results suggest that one molecule, berberine,
      can account for the majority of the anti-proliferative activity of C. rhizoma and
      that DNA microarray analyses can be used to improve our understanding of the
      actions of an intact herb.

PMID- 15964316
TI  - Evaluation of cytochrome P450 4 family as mediator of phospholipase D activation
      in aortic vascular smooth muscle cells.
AB  - Norepinephrine (NE) stimulates phospholipase D (PLD) activity via phospholipase
      A2-dependent arachidonic acid release in rabbit aortic vascular smooth muscle
      cells (VSMC). We have previously shown that exogenous 20-hydroxyeicosatetraenoic
      acid (20-HETE), an eicosanoid generated through the cytochrome P450 (CYP) 4A
      pathway in vivo, stimulates PLD activity. Whether endogenous CYP4-derived
      arachidonic acid metabolites act as intracellular mediators of NE-induced PLD
      activation in VSMC is not known. In rabbit aortic VSMC, prototypical
      hepatic/renal CYP4A inducers such as fenofibrate and Wy 14643 inhibited both
      basal and NE-induced PLD activity after 48 h of exposure. The level of CYP4F, and
      to a lesser extent CYP4A, was also decreased by these agents. The expression
      levels of rabbit aortic VSMC CYP4A and CYP4F isoforms were reduced by antisense
      oligonucleotides treatment for 48 hours as measured by RTQ-PCR or Western
      blotting. This reduction in CYP4A or CYP4F levels did not change NE-induced PLD
      activation. The corresponding CYP4A scrambled and CYP4F sense oligonucleotides
      did not alter CYP levels. PLD activity was increased by ~70% after 15 min of
      stimulation with NE, whereas lauric acid omega-hydroxylase activity, a measure of
      fatty acid omega-hydroxylation, was unchanged. Inhibition of omega-hydroxylation
      with DDMS and HET0016, selective omega-hydroxylase inhibitors, and 20-HEDE, an
      antagonist of 20-HETE, increased PLD activity in a concentration-dependent manner
      and did not alter NE-induced PLD activation. These data suggest that PLD
      activation by NE is independent of the CYP4A/4F enzymes in rabbit aortic VSMC.

PMID- 15964317
TI  - Pharmacokinetic interaction with digoxin and glucocorticoids in rats detected by
      radio-immunoassay using a novel specific antiserum.
AB  - We previously prepared a more specific antiserum (Antiserum-I) to digoxin (Dx)
      compared with commercially available anti-Dx antiserum (Antiserum-II), clinically
      used in the therapeutic drug monitoring of Dx. The aims of this study are to
      compare Dx disposition kinetics by radio-immunoassay (RIA) using Antiserum-I and
      Antiserum-II, and evaluate the drug-drug interaction with Dx and glucocorticoids
      in rats. When Dx metabolites were added to rat serum containing Dx, the recovery
      ratios using Antiserum-I showed 100 to 110% and were remarkably lower than those
      using Antiserum-II. In rats, serum concentration-time courses of Dx after a
      single i.v. or p.o. administration of Dx (0.017 mg/kg) by RIA using Antiserum-I
      were much lower than those using Antiserum-II. The area under the concentration
      time course of Dx was significantly lower than that using Antiserum-II and the
      total body clearance values were significantly higher, while an obvious change of
      bioavailability was not observed. When using Antiserum-I, rats twice and six
      times pretreated with dexamethasone (75 mg/kg/day, i.p.) and prednisolone (69
      mg/kg/day, i.p.), respectively, showed significant change of the pharmacokinetic
      parameters of Dx compared with the control rats. In contrast, using Antiserum-II,
      it took three and nine times of pretreatment with dexamethasone and prednisolone,
      respectively, to significantly change the parameters of Dx. In conclusion, these
      results demonstrate that Antiserum-I is very useful not only to more precisely
      monitor serum Dx levels, but also to determine earlier the drug-drug interaction
      with glucocorticoids than Antiserum-II.

PMID- 15964318
TI  - Challenges of organ transplantation.
AB  - Organ transplantation has developed in the past 50 years from a primitive
      therapeutic attempt to an accepted and much sought after form of treatment.
      During the same period, bone marrow transplantation, a form of cell
      transplantation, also has become established with similar successes provided the
      donor and recipient are well matched. The next challenges in transplantation are
      to overcome the donor shortage and to devise new ways of treating diseases that
      at present have unsuccessful management. The transplantation of cells programmed
      to produce essential proteins is an important goal, especially if the cells were
      autologous, for example, adult stem cells persuaded to produce insulin and act as
      surrogate beta cells. In this short article, I have reviewed some of the progress
      and difficulties of cell transplantation, which is currently a popular and
      intense area of research worldwide.

PMID- 15964319
TI  - Electrolytic disorders, hyperosmolar states, and lactic acidosis in brain-dead
      patients.
AB  - Despite the use of well-accepted protocols for donor maintenance, the severe
      electrolytic disorders are not infrequent with deleterious consequences to the
      organs. The objective of our survey was to determine the incidence of episodes of
      electrolyte disorders among brain-dead patients (despite of rigid protocols of
      maintenance) and the rate of anaerobic metabolism in these patients (suggestive
      of an occult systemic hypoperfusion). The study group of 50 brain-dead patients
      underwent therapy to maintain normal arterial pressure, urine output, and body
      temperature. Standard monitoring for brain-dead patients was followed, except for
      a frequent evaluation of electrolytes, including glucose, sodium, potassium,
      phosphorus, osmolality, base excess, and lactate plasma levels. Our results
      demonstrate that with frequent determinations of electrolytes, despite following
      strict protocols of maintenance, there was a high incidence of hyperglycemia,
      hypophosphotemia, hypokaemia, and hyperosmolality. Interesting findings were the
      high incidence of elevated lactate, and the relationship between lactate levels
      and bases deficit as well as hypernatremia. It can be concluded that, even
      following rigid protocols, the maintenance of brain-dead patients demands a close
      evaluation of electrolyte levels. Our results also suggest that the inclusion in
      the monitoring protocol of anerobic metabolism data including lactate levels can
      help to avoid occult ischemia of organs, and consequently improve their quality
      for transplantation.

PMID- 15964320
TI  - Brain death after severe traumatic brain injury: the role of systemic secondary
      brain insults.
AB  - Secondary brain insults predominantly due to hypotension are frequent among
      patients with fatal traumatic brain injury. We assessed the correlation between
      different systemic secondary brain insults and brain death in 404 patients
      admitted to our intensive care unit (ICU) after severe traumatic brain injury. We
      collated data on hypoxemia and hypotension prior to as well as the occurrence of
      hypoxemia, hypotension, shock, anemia, hyperglycemia, and hyperthermia within the
      first 24 hours after ICU admission. We also considered both the presence of
      extracranial injuries and the category of traumatic brain injury using
      computerized tomography. The 59 patients (14.6%) who developed brain death, were
      significantly older than patients without a fatal neurological outcome (46.1 +/-
      22 vs 29.5 +/- 14.9 years; P < .0001). Intracranial mass lesions, whether
      surgically evacuated were more frequent among brain-dead patients. The systemic
      secondary brain insults significantly associated with brain death were hypoxemia,
      hypotension, shock, anemia, and hyperglycemia within the first 24 hours after ICU
      admission. After multivariate analysis, the factors that independently predicted
      brain death were the occurrence of shock (odds ratio [OR], 6.74; 95% confidence
      interval [CI], 2.85-15.84; P = .001) and older age (OR, 1.05; 95% CI, 1.03-1.07;
      P = .003). In conclusion, early shock seems to be the major systemic secondary
      brain insult associated with brain death in patients with severe traumatic brain
      injury. Prevention of or correction of shock might help to either decrease the
      occurrence of a fatal neurological outcome or in brain-dead patients to preserve
      organs in better condition for procurement.

PMID- 15964321
TI  - Public knowledge and attitudes toward organ donation and transplantation: a cross
      cultural study.
AB  - OBJECTIVE: The aim of this study was to determine the knowledge, attitudes,
      awareness, and determinants of organ donation and transplantation in a Qatari
      population. DESIGN: This is a cross-sectional study to determine the knowledge
      and attitude toward organ donation in a Peninsula Arabian Gulf country. SETTING:
      The setting was Primary Health Care (PHC) Centers and community-based study in
      Qatar. SUBJECTS: A multistage sampling design was used in a representative sample
      of 1600 Qataris and non-Qataris, including males and females of at least 17 years
      of age, from October 2003 to May 2004. In this study a 1305 (81.5%) subjects
      participated, each giving consent for the study. MEASUREMENTS: Participants
      completed a questionnaire assessing their knowledge, attitudes, and awareness for
      organ donation. RESULTS: Of 1305 samples, 637 (48.8%) males and 668 females
      (51.2%) living in urban and semiurban areas agreed to participate and complete
      the questionnaire. Of these, 762 (58.4%) were Qataris. There was a significant
      difference between Qataris and non-Qataris with respect to their age, educational
      level, monthly income, and occupation. In this study, 31.6% of Qataris and 29.8%
      of non-Qataris had no idea about the organ donation; 37.8% of Qataris and 32.8%
      of non-Qataris were willing to donate their organs. The majority of subjects
      preferred donating organs to their close relatives and friends. However, 83.8% of
      the studied subjects did not agree with an incentive-based approach for donating
      organs. CONCLUSION: This study showed that people should not be blamed for not
      being willing to participate in organ donation, but the health system and health
      education providers are responsible. A more effective approach should be tried
      regarding health education.

PMID- 15964322
TI  - Outmoded attitudes toward organ donation among Turkish health care professionals.
AB  - AIM: Our goal was to investigate the attitudes toward and information regarding
      organ donation possessed by assistant and intern doctors and nurses. METHOD: A
      total of 70.4% of assistant doctors, 52.9% of nurses, and 94.3% of interns
      participated in this descriptive study. Participants were interviewed fact-to
      face to ask questions investigating profession; gender; age; whether they had
      donated organs; if so, which organ(s); if not, which organ(s) they would consider
      donating; if they would not consider such donation the reason why; whether they
      would donated another person's organs in the event of the death of a relative;
      and what their thoughts would be if they themselves required an organ transplant.
      RESULTS: Ten (2.2%) individuals had donated organs by applying to an official
      health institution. Of those participants who had not yet donated organs, the
      main reason cited for this were lack of information regarding the donation
      process (28.7%), concerns about the sale of organs (22.1%), and Islamic religious
      beliefs (21.6%). In the event that they themselves required an organ transplant,
      59.8% replied that they "would wish an organ transplant to be performed," and
      57.6% of those asked whether they would donate the organs of a deceased relative
      replied that they would not. CONCLUSIONS: The low level of donation among health
      care professionals, who should be in the forefront of organ transplantation, and
      the predominance of ethical and religious reasons for not donating, are
      incompatible with the present state of medicine.

PMID- 15964323
TI  - Prospective psychosocial evaluation of related kidney donors: Indian perspective.
AB  - With increasing acceptance of living organ transplantation and growing numbers of
      organ donors, it becomes important to look for any adverse outcomes in this
      population. Prospective psychosocial evaluation of living related donors and
      assessment of the outcome of donation process was done. We also tried to identify
      any risk factors associated with any adverse event. Between January 2003 and
      December 2003, 75 consecutive donors (mean age 42.8 +/- 11.6 years; M:F 54:21)
      were interviewed preoperatively and at 3 months postoperatively based on a 57
      item questionnaire. Objective assessment of anxiety, depression, and social
      support was done with "modified Beck's depression inventory," "Speilberg's state
      and trait anxiety," and "social support" questionnaires. The majority (85.3%) of
      donors had volunteered for donation. There were no major depressive or anxiety
      disorders following donation. Though 21.3% donors perceived some negative impact
      on their health, none regretted the decision to donate and most (96%) would
      encourage organ donation. Prolonged donor hospitalization, persistent pain, poor
      recipient reciprocation, or recipient death were associated with a poor
      psychosocial outcome.

PMID- 15964324
TI  - A proposed Saudi approach to the ethical utilization of living unrelated kidney
      donation.
AB  - We outline a proposal for the use of living unrelated kidney donors for
      transplantation. This proposal, although recommended by the Saudi National
      Committee on Renal Transplantation, is still under discussion and has not been
      implemented yet. We feel that this proposal is ethical with airtight safeguards
      against commercialization and for the protection of the well-being of the donor
      with assurance that he or she has not been coerced into donation.

PMID- 15964325
TI  - Play-back theatre, theatre laboratory, and role-playing: new tools in
      investigating the patient-physician relationship in the context of continuing
      medical education courses.
AB  - AIM: The aim of this study was to report on the validation of a role-playing
      approach, using play-back and theatre laboratory in the context of a continuing
      medical education (CME) course on predialysis and transplantation, to discuss the
      patient-physician relationship. METHODS: The course was developed with the help
      of a theatre director. The role-playing 2-day course was designed to be highly
      interactive for a small group (15-20 participants), based on a core of case
      reports (dialysis, transplantation, and return to dialysis after graft failure).
      Two stages were included: play-back theatre in which experiences told by the
      participants were mimed by a group of actors, and theatre laboratory in which
      different aspects of voice and touch were explored. Opinions were gathered by an
      anonymous semistructured questionnaire completed by all participants. RESULTS:
      The course obtained a high score from The Ministry of Health (14 credits, 1 per
      teaching hour). The opinions of the 18 participants were highly positive; all
      liked the courses. Sixteen of 18 asked to repeat the experience. The strong
      emotional involvement was an advantage for 15 of 18, sharing emotional aspects of
      the profession for 10 of 18, and usefulness in clarifying opinions on "dark
      sides" of our profession for 10 of 18. CONCLUSION: The positive opinions recorded
      during this experience, the first experiment with a "psycho-theatrical approach"
      developed in a CME course in our country, suggest the benefit of implementing
      nonconventional, educational approaches in a multidisciplinary discussion of the
      patient-physician relationship in transplantation medicine.

PMID- 15964326
TI  - Laparoscopic versus open donor nephrectomy in Germany: impact on donor health
      related quality of life and willingness to donate.
AB  - INTRODUCTION: Laparoscopic living donor nephrectomy (LDN) offers multiple
      advantages to the donor. Since 1999 LDN has become the only surgical approach for
      living kidney donation in our department. To our knowledge a donor health-related
      quality of life (QoL) has not yet been performed with standardized and validated
      questionnaires to compare laparoscopic with open nephrectomy. We therefore
      performed a study with two questionnaires (SF-36/GBB-24) and one set of open
      questions for all donors in our department. METHODS: Questionnaires were sent out
      to all donors between 1983 and 2001 with at least a 1-year follow-up. To exclude
      a bias a maximum response rate was sought; donors who did not answer were
      recontacted as well as their recipients or their physicians to motivate them for
      participation. RESULTS: The response rate was (89.8%). Except for less limb pain
      in the laparoscopy group, no difference could be detected for donors QoL with
      respect to the surgical method. Willingness to donate again was not affected by
      the surgical method. Nevertheless if asked again today, most donors want
      laparoscopic kidney retrieval. CONCLUSIONS: Donors health-related QoL is not
      affected by the surgical method when queried retrospectively. Nevertheless, most
      donors today would favor laparoscopy, if they could chose again. How laparoscopy
      affects a reluctant donor to step forward must be determined in a prospective
      study.

PMID- 15964327
TI  - Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin
      solutions as primary preservation in renal allografts undergoing pulsatile
      perfusion.
AB  - INTRODUCTION: University of Wisconsin (UW) solution is the standard preservation
      solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK)
      solution has been used increasingly for kidney, pancreas, and liver
      transplantation. This study compared HTK and UW used during kidney procurement
      with subsequent pulsatile perfusion. METHODS: Between January and October 2003,
      91 deceased renal and simultaneous kidney pancreas transplants were performed
      (UW, n = 41, and HTK, n = 50). There were no differences with regard to donor and
      recipient demographics or cold ischemia. RESULTS: Delayed graft function occurred
      in 3 (7%) of UW and 4 (8%) of HTK-preserved kidneys (P = NS). There were no
      significant differences between patient or graft survival. There was an
      anticipated difference between total preservative volumes used (HTK: 4.1 +/- 1.0
      vs UW: 3.0 +/- 0.5; P < .005). CONCLUSION: UW and HTK appear to have similar
      efficacy in kidney preservation with pulsatile perfusion. HTK preservation
      solution can be used safely in conjunction with pulsatile preservation for cold
      storage of renal allografts.

PMID- 15964328
TI  - A randomized study comparing combined spinal epidural or general anesthesia for
      renal transplant surgery.
AB  - INTRODUCTION: The appropriate anesthesia for renal transplantation requires
      minimal toxicity for patients and for the transplanted organ, as well as
      sufficient pain relief and maintenance of vital functions. The aim of this study
      was to determine how the anesthetic technique influences the outcome in patients
      after renal transplantation in terms of preoperative and intraoperative
      hemodynamic changes and blood gas changes. METHODS: Fifty adult patients
      undergoing renal transplantation were randomly divided into two groups receiving
      standardized general anesthesia or combined spinal and epidural anesthesia.
      RESULTS: Demographically both groups were similar. Total anesthesia time (202 +/-
      53 vs 186 +/- 37 minutes) and surgical time (191 +/- 52 vs 162 +/- 31 minutes)
      did not differ between the groups. The heart rate and systolic blood pressure
      values of the groups as measured before induction and 5, 15, 20, 30, as well as
      60 minutes thereafter did not differ between the groups. Neither the frequency of
      bradycardia (four vs two) nor of hypotension (six vs four) during anesthesia
      differed between regional versus general anesthesia groups. CONCLUSION: Regional
      is an important alternative to general anesthesia during renal transplantation
      surgery in adult patients.

PMID- 15964329
TI  - The effect of anesthetic technique on early postoperative renal function after
      donor nephrectomy: a preliminary report.
AB  - General and regional anesthesia may both be used successfully in donor
      nephrectomy although the use of regional anesthesia is rare. We compared the
      remaining kidney function during general (n = 10) versus combined spinal-epidural
      (n = 10) anesthesia for donor surgery. Blood biochemistry data were collected
      preoperatively and postoperatively, while renal function was assessed by
      scintigraphy and urine levels of microalbumin, creatinine, Na, K, Ca and
      creatinine clearance rate were measured/calculated in 24-hour urine samples
      collected preoperatively and on postoperative day 2. There were no differences
      preoperatively and on postoperative day 2 with respect to glomerular filtration
      rate, microalbuminuria, or creatinine clearance rate (P > .05 for all). There
      were also no differences between the groups with respect to other scintigraphic
      findings preoperatively and on postoperative day 2 (P > .05 for all). The results
      suggest that general or combined spinal-epidural anesthesia for donor nephrectomy
      have similar effects on the remaining donor kidney function.

PMID- 15964330
TI  - A laparoscopic approach to allograft nephrectomy and bilateral native
      nephrectomy: a case report.
AB  - INTRODUCTION: Laparoscopic surgery is rapidly emerging as the standard of care
      for a variety of urological conditions, even among patients who have undergone
      prior renal transplantation. We describe the technique of bilateral native
      nephrectomy and allograft nephrectomy by laparoscopy. CASE REPORT: A 32-year-old
      man with end-stage renal disease who had undergone a cadaveric renal transplant
      presented with chronic graft dysfunction. He had received a living donor kidney
      transplant with a postoperative course complicated by persistent proteinuria and
      refractory hypertension. Our nephrology service indicated the need for bilateral
      native nephrectomy and allograft nephrectomy for better blood pressure control
      following a second transplant. Bilateral native nephrectomy was performed
      following the previous reported techniques for pure laparoscopic nephrectomy.
      Allograft nephrectomy started by dissection of the iliac vessels to identify the
      vascular anastomosis. The hilum of the transplanted kidney was accessed. The
      renal vessels were clipped and transected. The ureter was identified and clipped.
      All three kidneys were removed from the abdominal cavity through a 3-cm skin
      incision. RESULTS: The left nephrectomy took 25 minutes and the right
      nephrectomy, 40 minutes. The estimated blood loss was 300 mL and the total
      operative time was 210 minutes. The patient had an uneventful postoperative
      course and was discharged on the third postoperative day. CONCLUSIONS: We
      demonstrate the feasibility of laparoscopic allograft nephrectomy and bilateral
      native nephrectomy in a transplant recipient.

PMID- 15964331
TI  - Campath-1H as rescue therapy for the treatment of acute rejection in kidney
      transplant patients.
AB  - INTRODUCTION: Kidney transplant patients with acute rejection episodes refractory
      to antilymphocyte preparations require aggressive treatment to salvage renal
      function and reduce the progression of chronic allograft nephropathy. PATIENTS
      AND METHODS: During a 6-month period, we administered Campath-1H as salvage
      therapy to five patients who had been previously treated with thymoglobulin
      and/or OKT3. In addition to measurements of the serum creatinine and BUN levels,
      we estimated creatinine clearance and glomerular filtration rates (GFR) using the
      Cockcroft-Gault and the MDRD equations at the time of initiation of therapy as
      well as at 2 weeks and 2 months thereafter. RESULT: Four of the five patients
      responded to Campath-1H therapy; kidney function improved to nearly the level
      before the rejection episode. The estimated creatinine clearance increased
      approximately threefold and the GFR approximately fourfold higher than the values
      before Campath-1H administration. The adverse events were mild and self-limited.
      CONCLUSION: Salvage of refractory acute rejection episodes may be possible in
      selected patients using Campath-1H.

PMID- 15964332
TI  - Blood cyclosporine level soon after kidney transplantation is a major determinant
      of rejection: insights from the Mycophenolate Steroid-Sparing Trial.
AB  - Target organs express antigens directly recognized by antigen-specific T cells,
      thereby precipitating rejection. When early T-cell activation is inhibited, there
      is a low risk of rejection. We sought to determine the predictive values of
      serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize
      the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug
      concentrations. The final aim of the study was to identify a concentration range
      for the best predictive pharmacokinetic parameter that should be targeted to
      reduce the risk of rejection. This possibility was explored in 334 de novo kidney
      transplant recipients who participated in the prospective, multicenter
      Mycophenolate Steroid-Sparing Trial. Among measurements performed during the
      first 6 months postsurgery, cyclosporine C(0) levels measured early after
      transplantation were the strongest predictor of acute graft rejection. Levels
      within 300 to 440 ng/mL were associated with the lowest risk of rejection, while
      patients with levels lower than 300 ng/mL showed a more than double risk.
      Cyclosporine trough values predicted allograft rejection with an accuracy of 74%,
      while C(2) levels had no predictive value. These findings underline the need to
      target cyclosporine therapy early posttransplant to modulate T-cell activation.

PMID- 15964334
TI  - Factors contributing to acute rejection in renal transplantation: the role of
      noncompliance.
AB  - Early episodes of acute rejection after renal transplantation reflect inadequate
      immunosuppression at a time of heightened immune challenge. Late acute rejection
      episodes, however, are less likely related to inadequacy of immunosuppression and
      may be due to patient noncompliance or overzealous weaning of immunosuppression.
      We evaluated 443 consecutive renal transplant recipients to determine the
      incidence and etiology of acute rejection. All episodes were confirmed by
      ultrasound-guided biopsy. The cause of each acute rejection was determined by
      chart review. Medication compliance was determined by history at the time of
      admission for biopsy. Over a follow-up period of 42 +/- 22 months, 87 patients
      (20%) suffered acute rejection. There was a trend toward fewer episodes of acute
      rejection with thymoglobulin induction and tacrolimus-based immunosuppression.
      Younger recipients had an increased risk of acute rejection (odds ratio 0.47,
      range 0.24-0.91, P = .027). Patient noncompliance with immunosuppression was
      associated with late acute rejection (P = .0002). Acute rejection increased the
      risk of allograft failure (P < .0001). Modifiable factors, including the choice
      of immunosuppression, reduce the risk of acute rejection. More importantly, the
      transplant recipient plays a substantial role in the maintenance of their
      allograft health through compliance with immunosuppressive drug therapy. Future
      strategies to improve compliance, including increased vigilance in high-risk
      patient groups, frequent medication review, and laboratory testing, should be
      encouraged.

PMID- 15964333
TI  - IL-2 and TNF-alpha promoter polymorphisms in patients with acute kidney graft
      rejection.
AB  - INTRODUCTION: Proinflammatory cytokines have been implicated in the pathogenesis
      of acute kidney allograft rejection. The aim of the study was to examine the
      association between interleukin (IL)-2 -330 and tumor necrosis factor (TNF)-alpha
      -308 promoter polymorphisms and acute kidney allograft rejection. METHODS: The
      study included 72 patients with long-term stable graft function, and 57 diagnosed
      with acute kidney allograft rejection. RESULTS: Patients with acute kidney
      allograft rejection showed a prevalence of subjects with TNF-alpha T2 allele (P <
      .05). The risk of acute kidney allograft rejection diagnosis was 2.5-fold greater
      among carriers of the T2 allele than those homozygous for T1T1 (OR 2.53, 95% CI
      1.19 to 5.37, P < .05) There was no statistically significant difference in the
      distribution of IL-2 genotypes between patients with stable graft function and
      acute kidney allograft rejection. CONCLUSION: The results suggest that TNF-alpha
      308 promoter polymorphism is a risk factor for acute kidney allograft rejection.

PMID- 15964335
TI  - Differences in reporting of acute rejections between American and European
      publications of large immunosuppressive trials impair comparability of study
      results.
AB  - This study examined the use of different definitions for acute rejection in
      recent large multicenter trials performed in America and Europe in order to
      assess whether systematic differences exist between both scientific cultures. We
      systematically selected recent publications on multicenter randomized controlled
      trials, investigating immunosuppressive regimens in de novo kidney transplant
      recipients. Publications included were classified according to the type of acute
      rejection reported: group 1 reported no or only one type of rejection rate
      (biopsy-proven or treated); group 2 reported information on both treated and
      biopsy-proven rates. Other potential factors (journal's impact-factor, study
      size) were compared within the subgroups. To determine the rates of treated but
      not biopsy-proven acute rejections, additional analyses were performed within
      subgroup 2. The reviewed publications were 24/44 (54.5%) European (E) and 20/44
      (45.5%) American (A) origin. Eighteen of 44 publications reported no or only one
      type of rejection rate (group 1); 26 publications reported treated as well as
      biopsy-proven rates (group 2). Significantly more European publications reported
      both treated and biopsy-proven rates (E: 18/24 [75.0%] vs A: 8/20 [40.0%]; P =
      .019). Group 1 American papers were published in higher-ranked journals than
      European ones. The rate of blindly treated rejections did not differ
      significantly (A: 6.13% [range 0% to 12.8%] vs E: 8.43% [range 0% to 16.9%]) and
      the proportion of blindly treated rejections was slightly lower in American
      studies (A: 18.5% vs E: 26.5%). Our systematic review showed large discrepancies
      with a trend to report biopsy-proven rejection rates only in recent years.

PMID- 15964336
TI  - Different evolution of trough and dose levels during the first year after
      transplantation for tacrolimus versus cyclosporine.
AB  - At present, the two calcineurin inhibitors-cyclosporine (CsA) and tacrolimus
      (FK506)-are among the most frequently used immunosuppressants in clinical
      transplantation. Both drugs share variable oral bioavailability, which
      necessitates intense drug monitoring. This variability is attributed to large
      interindividual differences in drug catabolism by cytochrome P450 3A4/5
      (CYP3A4/5) and drug efflux by P-glycoprotein (PGP). In addition, the activity of
      both CYP3A4 and PGP can vary substantially within the same individual due to
      environmental factors such as concomitant intake of inducing/inhibiting
      medications (eg, rifampicin/sporanox) or food substances (eg, grapefruit juice).
      More recently, an inducing effect of methylprednisolone on intestinal and hepatic
      CYP3A4 has been shown. Also, an influence of gender on CYP3A4 activity (being
      higher in women) has been reported. Once CsA and FK506 are absorbed and reach the
      bloodstream, both drugs are avidly bound to erythrocytes (up to 95% for FK506 and
      50% for CsA) and plasma proteins, leaving only a small fraction of circulating
      active drug. This phenomenon also limits further hepatic catabolism and hence
      clearance of drug, which is influenced by hematocrit and levels of plasma
      proteins such as albumin. The aim of the present study was to compare the
      influence of changing steroid doses, hematocrit, and albumin on trough and dose
      levels of FK506 versus CsA during the first year after transplantation. In
      addition, the evolution of trough and dose levels of FK506 versus CsA was
      stratified according to gender.

PMID- 15964337
TI  - Delayed renal graft function: the influence of immunosuppression.
AB  - INTRODUCTION: We evaluated the influence of different immunosuppressive regimens
      on delayed renal graft function and progression of renal function in the first
      year after transplantation. PATIENTS AND METHODS: Patients were divided into four
      groups according to the immunosuppressive regimen received: (1) rapamycin (Rap) +
      mycophenolate mofetil (MMF) + methylprednisolone (MP) + daclizumab (Dmab); (n =
      44); (2) tacrolimus (Tac) + MMF + MP + Dmab (n = 39); (3) cyclosporine (CsA) +
      MMF + MP + basiliximab (Bmab); (n = 30); (4) antithymocyte globulin (ATG) + MMF +
      MP and CsA after ATG withdrawal (n = 40). Data were analyzed using ANOVA and
      linear regression. Delayed graft function was defined as the need for
      hemodialysis posttransplantation. RESULTS: There were no statistically
      significant differences between the four groups in terms of gender, time on
      dialysis before transplantation, histocompatibility, donor age, and cold ischemia
      time. However, age (49.8, 50.4, 49.8, and 43.5 years, P < .05), panel reactive
      antibodies (22%, 39%, 27%, 34%, P < .05) and time of delayed graft function (12,
      7, 3, 6 days, P < .05) were significantly different between the four groups. The
      time of delayed graft function depended on the immunosuppressive regimen, as well
      as donor and recipient age (P < .05). The creatinine clearance demonstrated a
      statistically significant difference between the four groups in the first month
      after transplantation (45, 46, 61, 53 mL/min, P < .05), though no further
      difference was observed at the month 12th. CONCLUSIONS: The type of
      immunosuppressive therapy seems to substantially influence the time of recovery
      from delayed renal graft function, even though it does not seem to affect future
      graft function. Especially Rap, probably due to its potent antiproliferative
      effects, seems to prolong the length of graft recovery after renal
      transplantation.

PMID- 15964338
TI  - Comparison of long-term actual renal allograft survival in mycophenolate mofetil
      and azathioprine-based triple drug immunosuppression protocols.
AB  - INTRODUCTION: The use of mycophenolate mofetil (MMF) in renal transplantation
      results in a 50% lower incidence of acute rejection compared to azathioprine
      (AZA). However, the graft survival reports are conflicting: the European trial
      and US database analysis suggest better survival with MMF, an observation that
      was not seen in the US and tricontinental studies. METHODS: We retrospectively
      reviewed our single-center experience (60% African-Americans) comparing the serum
      creatinine (SCr) values and 3-year actual graft survival with MMF versus AZA
      based immunosuppression. Group I included patients transplanted between January
      1990 and December 1992 on cyclosporine (CSA), AZA, and steroids; group II
      subjects, from January 1996 to December 1998 on CSA, MMF, and steroids. We
      analyzed SCr and all causes of graft losses at 3, 6, 12, 18, 24, and 36 months
      posttransplantation. RESULTS: The patient demographics were similar in both
      groups as was the mean SCr values at different times. The time-group interaction
      for SCr, the Kruskal-Wallis test for SCr for different categories (<1.5, 1.5 to
      2.0, 2.0 to 2.5, and >2.5 mg/dL) and the all-cause graft loss between the two
      groups were not significantly different. CONCLUSION: Our results failed to show
      better long-term actual graft survival despite the 6-year interval between the
      two groups. These findings agree with the results of the United States and the
      tricontinental studies. A lower incidence of acute rejection early after
      transplantation observed with MMF may not always translate into a long-term
      benefit, possibly due to the influence of nonimmunological factors, such as
      hypertension, calcineurin inhibitor toxicity, more frequent cytomegalovirus
      infections, and increased attempts to withdraw steroids using MMF-based
      protocols.

PMID- 15964339
TI  - Diffuse vascular damage in a transplanted kidney: an indication for nuclear
      magnetic resonance?
AB  - Vascular lesions are an increasing challenge after renal transplantation due to
      the wider indications for recipients and acceptance criteria for donors.
      Diagnostic approach and prognostic interpretation are still matter of
      controversy. The case reported herein may summarize some of the issues in this
      regard. A 54-year-old woman, on renal replacement therapy since 1974, and a
      kidney graft recipient from 1975 to 1999, received a second graft in 2001. The
      donor age was 65 years (cold ischemia 22 hours; two mismatches). The early
      posttransplant follow-up was characterized by delayed graft function,
      hypertension, and diabetes. During the initial hypertension workup, renal graft
      ultrasound (US) Doppler demonstrated increased vascular resistances, stable over
      time (resistance index 0.74 to 0.77); renal scintiscan displayed homogeneously
      parenchymoa and angio-magnetic resonance imaging (MRI), an homogeneous
      parenchymal vascularization. Initial immunosuppression with tacrolimus and
      steroids was modulated by adding mycophenolate mofetil to taper tacrolimus (to
      reduce nephrotoxicity and hypertension). Despite this, kidney function slowly
      deteriorated; serum creatinine reached 3 to 3.5 mg/dL by the second year. After a
      severe hypertensive crisis with unchanged scintiscan and US doppler examinations,
      angio-MRI revealed the almost complete disappearance of parenchymal enhancement
      beyond the lobar arteries. A renal biopsy confirmed the severe vascular damage.
      The patient was switched to rapamycine and a low-dose of an angiotension
      converting enzyme (ACE) inhibitor. She did relatively well (serum creatinine 2.2
      to 3 mg/dL) for 6 months, when rapid functional impairment forced her to restart
      hemodialysis. This case, almost paradigmatic of the problems occurring when the
      rigid vasculature of long-term dialysis patients is matched with "marginal
      kidneys," suggests that MRI may be a sensible good to define vascular damage in
      the grafted kidney.

PMID- 15964340
TI  - Early experience with enteric-coated mycophenolate sodium in de novo kidney
      transplant recipients.
AB  - INTRODUCTION: We sought to evaluate the efficacy of enteric-coated mycophenolate
      sodium (EC-MPS) and the gastrointestinal (GI) adverse events in de novo kidney
      transplant recipients. METHODS: This noncontrolled, retrospective review includes
      22 de novo kidney transplant recipients. All patients received a standard course
      of basiliximab and were maintained on triple-drug therapy with EC-MPS,
      cyclosporine microemulsion (CsA), and prednisolone. The follow-up lasted 7.9 +/-
      1.2 months. The incidence of GI adverse effects were compared with those of
      historical mycophenolate mofetil (MMF) studies. RESULTS: The serum creatinine was
      maintained within 1.4 +/- 0.7 mg/dL. The 2-hour CsA postdose level was 1080 +/-
      327 ng/mL initially and gradually tapered to 851 +/- 435 ng/mL. The daily EC-MPS
      dose was 1404 +/- 180 mg initially and gradually tapered to 1098 +/- 288 mg. The
      GI adverse effects at the daily dose of EC-MPS 1422 +/- 126 mg included dyspepsia
      27%, acid regurgitation 18.2%, epigastralgia 9%, nausea 9%, vomiting 4.5%, and
      poor appetite 4.5%. In comparison those from historical MMF 2 g/d studies
      included dyspepsia 3.1% to 40%, epigastralgia 10%, nausea 3.7% to 34%, and
      vomiting 0.6% to 10.7%. CONCLUSION: Immunosuppression with CsA, EC-MPS, and
      steroids maintains stable graft functions. Minimal dose reduction of EC-MPS
      decreases GI adverse events but without significance. EC-MPC and MMF have
      respective GI side effects; they can be used alternatively in patients with
      individual GI intolerance.

PMID- 15964341
TI  - The cost-effectiveness of basiliximab induction in "old-to-old" kidney transplant
      programs: Bayesian estimation, simulation, and uncertainty analysis.
AB  - INTRODUCTION: Markov models are employed in economic analyses to evaluate all
      possible expectations in a dilemna. The introduction of a new clinical protocol
      (Basiliximab induction with calcineurin-sparing protocols) for a group of kidney
      transplant recipients receiving organs from marginal donors was validated with a
      Markov simulation model, demonstrating the usefulness of combining simulation
      with Bayesian estimation methods for analysis of cost-effectiveness data
      collected alongside a clinical trial. We sought to determine whether calcineurin
      sparing protocols using anti-interleukin-2/antibody induction (Simulect) would
      show a beneficial effect on initial kidney function and reduce transplantation
      costs upon admission, clinical incidences, graft function, and complications
      during the first month after transplant. PATIENTS AND METHODS: A Markov Chain
      Monte Carlo (MCMC) was used to estimate a system of generalized linear models
      relating costs and outcomes to a kidney transplant process affected by treatment
      under alternative therapies. The Markov simulation model was established
      following three chains: a calcineurin-free regimen with Basiliximab induction
      (chain A); a calcineurin-sparing protocol with Basiliximab induction (chain B);
      and a conventional immunosuppressive regimen (chain C). The MCMC draws were used
      as parameters in simulations that yielded inferences about the relative cost
      effectiveness of the novel therapy under a variety of scenarios. After designing
      the Markov chain and cohorts, 31 patients from the "old-to-old" program were
      assigned; eight to chain A; eight to chain B; and 15 to chain C. A year after
      transplantation a cost-benefit study was performed guided by the three branches
      of the Markov model. RESULTS: The Markov model showed a benefit of induction
      therapies in elderly patients. A cost-benefit model showed that after a year,
      there was a clear benefit from calcineurin-free plus Basiliximab induction
      therapies, with a slight benefit from calcineurin-sparing protocols. CONCLUSIONS:
      Markov models are extremely useful when introducing new clinical therapies. The
      approach allows flexibility in assessing treatment using various premises and
      quantifies the global effect of parametric uncertainty on a decision maker's
      confidence to adopt one therapy over another. In our transplant program, a cost
      effective analysis of outcomes in old patients using the Markov model showed a
      clear benefit of calcineurin-sparing protocols with Basixilimab induction.

PMID- 15964342
TI  - Quality of sleep and quality of life in renal transplantation patients.
AB  - INTRODUCTION: Sleep and sleep-related disorders are common among end-stage renal
      disease patients. In the general population and hemodialysis patients, insomnia
      impairs health-related quality of life (HRQOL). The aims of this study were to
      examine the prevalence of sleep problems among renal transplantation patients and
      the relationship between the quality of sleep and the HRQOL. METHODS: Pittsburgh
      Sleep Quality Index (PSQI) for measuring quality of sleep, WHOQOL-BREF for
      quality of life, and Beck Depression Inventory (BDI) were applied to 100 renal
      transplant patients. RESULTS: Thirty (30%) subjects were "poor sleepers" (global
      PSQI > 5). Poor sleepers were younger (mean age: 31 vs 37); less educated (mean
      years of education: 7.80 vs 9.55), and more depressed (mean BDI scores 13.63 vs
      7.18). There were significant inverse correlations between global PSQI and
      physical health (r = -0.31; P < .001) and psychological state (r = -.20; P = .04)
      with a significant correlation with BDI scores (r = .36; P < .001). The BDI score
      (P < .001) was the only significant factor of physical health, psychological
      state, and social functioning. BDI score (P < .001) and education (P < .022) were
      significant predictors of environmental conditions. CONCLUSION: Sleep problems
      are not as common among transplant as dialysis patients, but still higher than
      the general population. Poor sleep seems to be a part of depressive
      symptomatology. Severity of depression and lower education were more negatively
      effective factors on the quality of life of these patients than the quality of
      sleep.

PMID- 15964343
TI  - Diabetic retinopathy before and after renal transplantation: a longitudinal
      study.
AB  - Retinal evaluation was performed in 20 consecutive type 2 diabetics before and
      after renal transplantation. This included 19 men and 1 woman of mean age 52
      years (range 30 to 60 years). Before renal transplantation, 95% of these patients
      showed diabetic retinopathy (50% nonproliferative and 45% proliferative diabetic
      retinopathy). There was no change in retinopathy at 3 months after renal
      transplantation. At 1 year, two patients (10%) showed deterioration in their
      diabetic retinopathy, while the remaining 90% did not show any change. Also 25%
      of renal allograft recipients developed posterior capsular cataracts.

PMID- 15964344
TI  - Lack of impact of hepatitis C virus coinfection in end-stage renal disease
      patients with hepatitis B virus infection.
AB  - INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection
      results in more severe forms of liver disease in nonuremic patients; however, the
      impact of HCV coinfection is not clearly known in end-stage renal disease (ESRD)
      patients with HBV infection. We sought to determine the impact of HCV coinfection
      in HBV-infected ESRD patients. PATIENTS AND METHODS: The HBsAg-positive ESRD
      patients evaluated between March 1999 and May 2003 were divided into two groups:
      group B, HBV infection alone, and group BC, HBV-HCV coinfection (anti-HCV
      positive). Both groups were compared regarding epidemiological, laboratory, and
      histological findings. A liver biopsy was obtained in cases with evidence of
      viral replication and/or elevated alanine aminotransferase. RESULTS: One hundred
      patients (73% men) with mean age of 42 +/- 11 years (55 patients in group B and
      45 in group BC) were studied. Comparison between groups showed a difference in
      time on hemodialysis and duration of infection, which were higher in group BC (P
      < .001 and P = .001, respectively) and in history of blood transfusion, which was
      also more frequent in group BC (P = .04). Liver biopsies, obtained from 15
      patients in group B and 28 patients in group BC, showed no difference in
      frequency of septal fibrosis (60% in group B vs 48% in group BC, P = .46) or
      interface hepatitis (73% vs 71%, P = .99). CONCLUSIONS: HBV-HCV coinfection was
      related to a longer time on hemodialysis, longer duration of infection, and
      history of blood transfusion. Contrary to nonuremic patients, HCV coinfection was
      not associated with more severe forms of liver disease in ESRD patients.

PMID- 15964345
TI  - Hepatitis C virus reactivation in anti-hepatitic C virus-positive renal
      transplant recipients.
AB  - From 1992 to 2001 hepatitis C virus (HCV) viremia was studied in 53 renal
      transplant recipients anti-HCV+ with at least 3 months follow-up posttransplant
      using a quantitative retrotranscriptase-PCR method. HCV-RNA was detected in 45
      (85%): 29 of the 34 recipients treated with azathioprine-based therapy and 15 of
      18 treated with mycophenolate mofetil. Immunosuppressive therapy type did not
      affect HCV replication. Three different patterns of HCV-RNA evolution were
      detected: 13 (28.8%) patients with high RNA-HCV levels; 21 (46.7%) patients with
      low levels; and 11 (24.4%) patients with viremia elevation. In 10 (90%) of 11 of
      the last group, HCV viremia was detected before 15 days posttransplantation,
      significantly earlier than in the other two groups. Thus, replication during the
      first 15 days after transplantation leads to a high RNA-HCV viral load. No
      clinical symptoms were related to HCV.

PMID- 15964346
TI  - Hepatocellular carcinoma in renal transplant patients.
AB  - INTRODUCTION: Chronic liver diseases, especially those related to hepatitis B
      (HBV) and C viruses (HCV), are a common problem in renal transplant patients.
      Hepatocellular carcinoma (HCC) is a complication of chronic liver diseases,
      incidence in the renal transplant cohort is higher than in the general population
      (1.4% to 4% vs 0.005% to 0.015%). METHODS: We retrospectively evaluated the
      incidence of HCC, its clinical presentation, the treatments, and the relation to
      chronic viral hepatitis among the population transplanted at our center between
      January 1980 and December 1998 and followed to August 2003. RESULTS: During the
      study period, six recipients among 534 renal transplants displayed HCC (incidence
      1.12% of the entire population and 2.29% of patients with chronic viral
      hepatitis). Among the cohort five were men, and all had chronic viral hepatitis:
      three HBV, one HCV, and 2, a coinfection. HCC was diagnosed 124.1 (range 45 to
      244) months after transplantation. All patients presented with abnormal liver
      function tests and tumors larger than 5 cm. Four had more than three tumors and
      three had an alpha-fetoprotein level higher than 400 IU/mL. Three patients
      received no treatment (survivals 1, 1, and 4 months); two patients,
      chemoembolization (survival 6 and 12 months); and one, surgical ethanol
      injections (survival 4 months). The overall survival was 4.5 months. CONCLUSION:
      HCC in renal transplant recipients is a common complication among patients with
      chronic viral hepatitis. The outcome was poor because HCC was detected at an
      advanced stage. Screening strategies for early diagnosis must be prospectively
      evaluated.

PMID- 15964347
TI  - Therapy and prognosis of tumors of the genitourinary tract after kidney
      transplantation.
AB  - There is an increased incidence of tumors of the genitourinary tract among kidney
      graft recipients. From 1979 to 2001, all patients who received kidney transplants
      had records of both their underlying diseases and their initial
      immunosuppression. Patients who developed a genitourinary tract malignancy were
      evaluated for tumor type, location, stage, tumor therapy and clinical course.
      During this period, 1804 patients underwent 2068 kidney transplantations. Thirty
      four patients had 39 tumors of genitourinary origin. One patient was lost to
      follow-up. There were 15 patients with 18 renal cell carcinomas (one of them
      multifocal): six had seven transitional cell carcinomas; six, prostatic
      carcinoma; six, tumor of the female genital tract (one also had a renal cell
      carcinoma); and two, a seminoma. Most tumors were diagnosed in their early stages
      (< or = pT3, N0, M0; n = 31 tumors) and thus accessible to curative therapy,
      achieving good long-term results: 1- and 5-year survival rates of 100% and 91%,
      which were better than those obtained in advanced stages (N+, M+; n = 7 tumors),
      namely both 1- and 5-year survival rates of 38% (P < .05). Death was caused by
      tumor growth in nine patients (27%) and by other causes in three patients (9%).
      With appropriate treatment genitourinary tumors at early stage show a good
      prognosis. New immunosuppressants with supposed antiproliferative effects may
      help to decrease the incidence of malignancies. The most important factor is risk
      adapted screening to identify malignancies early and to initiate appropriate
      therapy.

PMID- 15964348
TI  - Multiple neoplastic lesions of the lower genital tract in a human papilloma virus
      infected kidney-pancreas allograft recipient: a case report.
AB  - States of immunodeficiency are associated with an increased rate of certain
      cancers. Immunosuppressed allograft recipients are at high risk of Human
      Papilloma Virus (HPV)-related de novo malignancies. A female pancreas plus kidney
      transplant patient developed multiple genital malignancies within 6 years. The
      genome of human papilloma virus type 16 was detected in malignant lesions
      obtained from surgical procedures. All detected lesions were removed at an early
      state of development.

PMID- 15964349
TI  - Experiences in kidney transplantation with duplicated ureters.
AB  - INTRODUCTION: The purpose of this study was to evaluate the complications of
      duplicated ureters in renal transplant recipients. METHODS: Between 1983 and
      2004, 12 patients (median age 34 years) received renal transplants from donors
      with duplicated ureters. In four patients the ureter to bladder anastomoses were
      performed separately according to the method described by MacKinnon, including
      two cases transplanted with ureteral catheters because of narrow widths. In the
      following cases of eight duplicated ureters an anastomosis was performed between
      the distal part of each ureter to form a common ureteral ostium, which was
      connected to the urinary bladder. A ureteral catheter was used to the splint
      ureterovesical anastomosis. RESULTS: No graft loss to ureteral complications was
      observed. There was no ureteral necrosis in the postoperative period. No clinical
      symptoms of ureteral junction obstruction were revealed after removing the
      ureteral catheter. By ultrasound examination four patients showed a slight
      temporary pyelocaliectasis was observed and four patients developed temporary
      urinary fistulas. CONCLUSION: Our ureterocystoneostomy procedures with duplicated
      ureters were safe and useful in kidney transplantation.

PMID- 15964350
TI  - Sildenafil citrate treatment for erectile dysfunction after kidney
      transplantation.
AB  - OBJECTIVE: Our goal was to analyze the morbidity of organic erectile dysfunction
      (ED) in kidney-transplant patients and to evaluate the efficacy and reliability
      of sildenafil citrate treatment. METHOD: Sixty-five ED patients with normal graft
      function for 3 to 12 months after kidney transplantation were involved in our
      study. Erectile dysfunction was diagnosed in all the patients by the
      International Index of Erectile Dysfunction (IIEF). Among them, 10 patients were
      in light degree; 32 patients in moderate degree, and 23 patients in severe degree
      according to IIEF score. All of the patients underwent medical history, physical
      and chemical examinations. In each patient, the IIEF score, blood urea nitrogen,
      creatinine, and trough concentrations of cyclosporine were compared before and
      after taking sildenafil citrate at an initial dose of 50 mg every night. RESULTS:
      Twenty-six patients without ED before transplantation suffered ED after the
      operation, and 32 patients with ED before transplantation noticed worsening.
      Taking sildenafil citrate was effective in 53 patients (81.54%). There were no
      statistical differences in blood urea nitrogen, creatinine, or trough
      concentrations of cyclosporine in patients before and after sildenafil treatment.
      CONCLUSIONS: The morbidity of organic erectile dysfunction increased after
      transplantation. Sildenafil citrate treatment for ED in kidney-transplant
      patients was effective and safe. Graft function and trough concentrations of
      cyclosporine were not affected by sildenafil citrate.

PMID- 15964351
TI  - Management of coralliform lithiasis on renal allograft with bricker-type
      ureterointestinal anastomosis.
AB  - PURPOSE: The authors report the management of a coralliform lithiasis that
      occurred in a renal allograft in association with a Bricker ureterointestinal
      anastomosis for urinary diversion. MATERIALS AND METHODS: A 58-year-old patient
      with a significant previous urological history, ie, surgery for childhood
      incomplete bladder extrophy, trans-ileal Bricker type ureterostomy, and in the
      end a renal allograft, presented with hematuria and septicemia. Complete
      radiological examination revealed an obstructive upper tract coralliform
      lithiasis in the transplanted kidney. A percutaneous nephrolithotomy also was
      performed for surgical treatment. RESULTS: On postoperative day 2, a urinary
      fistula was observed at the nephrostomy orifice. The Bricker ureterointestinal
      anastomosis was located at the same level as the nephrostomy orifice, which
      maintained upper urinary high pressures as well as the fistula. CONCLUSIONS:
      Possible preexistent lithiasis in a donor kidney should not be overlooked. In the
      management of kidney stones larger than 3 cm, percutaneous nephrolithotomy
      remains the "gold standard" procedure even in cases of external urinary
      diversion. We proposed an original management of the previously described
      postoperative complication using a hyperpression drainage tube device in
      association with a JJ stent.

PMID- 15964352
TI  - Kidney preserving solutions containing lidocaine may increase urological
      complication rate after renal transplantation: an in vitro study.
AB  - OBJECTIVE: The frequency of urological complications after renal transplantation
      is up to 12%. Some authors consider that lidocaine addition to preservation
      solutions produces a favorable influence on allograft function. However,
      lidocaine may influence urinary tract epithelial cells. The aim of this work was
      to establish the influence of lidocaine on cultured primary rabbit urothelial
      cells (PRUC) as a tool to understand mechanisms of urological complications after
      kidney transplantation. DESIGN AND METHODS: A PRUC culture was established from
      an 8-month-old male rabbit bladder. The cells were cultured alone and then with
      in various concentrations of lidocaine for 24 hours or 1 hour. After an
      additional 24 hours, cell viability was assessed by the trypan blue exclusion
      test. Student's t test was used for statistical analysis, with significance set
      at P < .05. RESULTS: The cytotoxic effects of lidocaine on PRUC were
      concentration dependent. One-hour exposure of PRUC culture to 0.5 or 1.0%
      lidocaine decreased cell viability. Both lidocaine concentrations decreased cell
      viability in PRUC culture after a 24-hour incubation; even 0.25% lidocaine caused
      changes in the PRUC culture morphology after a 1-hour incubation. Cells became
      rounded and detached from the growth surface. No cells were observed in the
      monolayer after 1-hour incubation with 1% of lidocaine. CONCLUSIONS: The toxic
      effects of lidocaine on PRUC may forecast problems with supplementation of kidney
      preservation solutions, leading to impaired epithelial layer healing with an
      increased risk of urological complications.

PMID- 15964353
TI  - Percutaneous management of transplant ureteral fistulae is feasible in selected
      cases.
AB  - INTRODUCTION: Ureteral fistulae in renal transplants may develop as a consequence
      of compromised ureteral vascularity or from a technical factor related to the
      ureteroneocystostomy, the latter typically developing within the first 72 hours
      posttransplant. Recently, percutaneous nephrostomy drainage has been used with
      increasing frequency for the initial management. It alone can lead to resolution
      of the fistula in at least some patients. The aim of the study was the evaluation
      of endourological management of ureteral fistulae in renal transplants. MATERIAL
      AND METHODS: Between August 1981 and February 2004, 1000 adult recipients
      underwent renal transplantation. Sixteen out of 29 patients who developed
      ureteral fistulae were managed endourologically; 13, open surgery. The items
      recorded on these patients included the type of ureteroneocystostomy, the time to
      fistula diagnosis, the image technique, the type of ureteral stents, and the
      clinical evolution. RESULTS: The 13 patients who underwent open surgery did well.
      Endourological management of ureteral fistula was successfully performed in 10 of
      16 cases. In all of them percutaneous nephrostomy drainage with stenting of the
      ureter with a double-J catheter did not prove any advantage to no stent (66.6% vs
      57%). In 13 of these 16 patients in which the passage of contrast into the
      bladder was demonstrated, the fistula resolved in 10 cases (77%), while none of
      the three cases with no flow into the bladder were helped by this approach.
      CONCLUSION: Percutaneous techniques can provide definitive management for 62% of
      renal allograft patients who develop ureteral fistula beyond 72 hours after renal
      transplant.

PMID- 15964354
TI  - An unusual cause of ureteral obstruction in a renal transplant recipient:
      ureteric aspergilloma.
AB  - Mycotic infections in various organ transplant recipients represent severe and
      often fatal complications. Aspergillosis isolated from the urinary tract occurs
      quite infrequently in renal transplant recipients. Besides, fungus balls are rare
      causes of ureteral obstruction. We report a 51-year-old patient with the
      diagnosis of ureteral obstruction caused by aspergillosis in the early post-renal
      transplant period, who unfortunately died with the clinical picture of
      disseminated infection and its complications.

PMID- 15964355
TI  - Variation of CD4+ and CD8+ T lymphocytes as predictor of outcome in renal
      allograft recipients who developed acute respiratory distress syndrome caused by
      cytomegalovirus pneumonia.
AB  - INTRODUCTION: We investigated the variation of CD4+ and CD8+ T lymphocytes in
      renal allograft recipients who developed acute respiratory distress syndrome
      (ARDS) caused by cytomegalovirus (CMV) infection and their relationship to
      patients outcome. METHODS: Twenty one cadaveric renal allograft recipients who
      developed ARDS caused by CMV infection were enrolled in this study. CD4+ and CD8+
      T lymphocytes were examined in peripheral blood on five occasions: the admission
      day (day 0) to ICU as ARDS, day 5, day 10, day 15 in ICU, and discharge day. A
      value taken in the second month after transplantation was assumed to be the
      preinfection value. RESULTS: Among 13 surviving patients, the numbers of CD4+ and
      CD8+ T cells and their ratio increased as the patients recovered. The numbers of
      CD4+ T cells increased significantly on day 10, day 15, and at discharge day
      compared with day 0 (P < .05). The number of CD8+ T cells on discharge day and
      the ratios after day 10 were also significantly higher than those on day 0 (P <
      .05). In eight nonsurviving patients, the numbers of CD4+ and CD8+ T cells and
      their ratio was similar to day 0. The number of CD4+ and CD8+ cells after day 5
      and their ratio after day 10 were significantly lower than those of survival
      group (P < .05). CONCLUSION: The variations of CD4+ and CD8+ T lymphocytes and
      their ratio are useful indicators of the severity of disease and the outcome of
      patients with CMV infections accompanying ARDS after renal transplantation.
      Nevertheless, it may be helpful to evaluate the efficiency of ongoing treatment
      methods in these patients.

PMID- 15964356
TI  - Klebsiella pneumoniae peritonitis shortly after kidney transplantation.
AB  - We report a case of spontaneous bacterial peritonitis caused by Klebsiella
      pneumoniae in a 34-year-old male recipient shortly after kidney transplantation.
      On posttransplant day 10, the patient started complaining of severe abdominal
      pain and nausea. Body temperature was 38.4 degrees C. The abdomen was diffusely
      tender with rigidity and rebound. Laboratory data showed a normal erythrocyte
      sedimentation rate and serum creatinine level but a slightly elevated C-reactive
      protein concentration and leukocytosis of 36,200 cells/mm(3) with 88%
      neutrophils. Explorative laparotomy revealed diffuse purulent peritonitis without
      an intraabdominal source of infection, such as intestinal perforation. The
      peritoneal fluid revealed greater than 1000/mm(3) white blood cells and many gram
      negative bacilli. Fluid cultures yielded growth of Klebsiella pneumoniae. The
      patient responded to antibiotic therapy; he was discharged in good condition.
      This case report draws attention to the impaired host defense that may predispose
      to spontaneous bacterial peritonitis in renal transplant recipients and alerts
      the clinician to the possibility of this rare disease.

PMID- 15964357
TI  - Influence of ganciclovir prophylaxis on citomegalovirus, human herpesvirus 6, and
      human herpesvirus 7 viremia in renal transplant recipients.
AB  - In order to know the influence of ganciclovir (GCV) prophylaxis on
      cytomegalovirus (CMV) human herpesvirus (HHV)-6 and HHV-7 replication in renal
      transplant recipients, three groups were studies: 54 patients without GCV; 29,
      with short-term GCV prophylaxis (less than 30 days); and 51, with long-term GCV
      prophylaxis (more than 60 days). CMV viremia was more prevalent in the first
      group (74%, 55%, and 29%, respectively), but CMV replication was also found in 14
      patients during therapy, in the other two groups. The antiviral did not affect
      the prevalence of HHV-6 (67.2%) or HHV-7 (76%), but HHV-6 viremia appeared later
      (42 +/- 31 vs 21 +/- 25/38 +/- 29 days posttransplant) and was shorter (29 +/- 30
      vs 62 +/- 34/41 +/- 33 days) among patients with long-term GCV prophylaxis. On
      the other hand, CMV viremia was longer when HHV-6 replication was present (40 +/-
      25 days vs 18 +/- 16 days). In addition, HHV-7 DNA was detected in all patients
      with CMV disease.

PMID- 15964358
TI  - Laparoscopic cholecystectomy for renal transplants.
AB  - The diagnosis and management of cholelithiasis in renal transplant patients are
      subjects of debate. The purpose of this study was to evaluate the outcomes of
      laparoscopic cholecystectomy in renal transplant patients with symptomatic
      gallstone disease. The records of 155 kidney transplant patients were reviewed,
      including 16 patients who, underwent laparoscopic cholecystectomy. Shortest
      interval time between transplantation and cholecystectomy was 2 years. Surgical
      morbidity were seen in two patients (12.5%) with no mortality and no graft loss.
      In conclusion, laparoscopic cholecystectomy can be performed safely with low
      morbidity in renal transplant patients who have symptomatic gallstone disease.
      The morbidity rate is comparable to nontransplant patients.

PMID- 15964359
TI  - The role of cholecystectomy in renal transplantation.
AB  - INTRODUCTION: We reviewed our clinical experience to assess the role of
      cholecystectomy transplant candidates pre- and posttransplantation. METHODS:
      Between April 1986 and December 2003, 57 (6.8%) candidates among 839 kidney
      transplants were found during routine pretransplant screening to show gallstones.
      RESULTS: Thirty nine (68.4%) symptomatic patients underwent cholecystectomy
      before transplantation. Among 18 (31.6%) asymptomatic patients monitored after
      transplantation, the 7 (39%) who developed biliary tract symptoms underwent
      laparoscopy or minilaparocholecystectomy without postoperative morbidity,
      mortality, or graft loss. CONCLUSIONS: Symptomatic gallstones have to be treated
      using the laparoscopic cholecystectomy or minilaparotomy technique. In
      asymptomatic cholelithiasis prophylactic cholecystectomy is only reserved for
      patients with biliary "intrinsic" risk factors. An early diagnosis and prompt
      surgical treatment yields good results.

PMID- 15964360
TI  - Increased expression of renin in chronic allograft nephropathy.
AB  - BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of renal
      transplant failure in the first decade posttransplant. The precise pathogenetic
      mechanism for CAN is not completely understood. A possible role of renin
      angiotensin system for CAN has been suggested through clinical observations that
      angiotensin-converting enzyme inhibition and angiotensin II receptor blockers
      prevent CAN. METHODS: Distribution of renin-positive cells in allograft biopsy
      specimens was examined immunohistochemically in 23 renal transplant recipients
      diagnosed with CAN Biopsy specimens obtained from seven recipients with stable
      renal function were examined as controls. Histologic evaluation was performed
      based on the Banff 97 classification. RESULTS: Renin-positive cells were found in
      the juxtaglomerular apparatus (JGA) adjoining the afferent arterioles in both
      groups. When the number of renin-positive cells in JGA was defined as a renin
      index, it was significantly higher in the CAN than the control group (P = .007).
      There was no significant difference in age, interval between transplantation and
      biopsy, and blood pressure between groups. Only a significantly higher serum
      creatinine was found in the CAN group. CONCLUSIONS: The increased renin-positive
      cells in JGA suggest a significant role of the intrarenal renin-angiotensin
      system activation in the development of CAN.

PMID- 15964361
TI  - A simulation model to investigate the impact of cardiovascular risk in renal
      transplantation.
AB  - Premature cardiovascular (CV) disease is the leading cause of death following
      renal transplantation and, as a consequence of death with a functioning graft, it
      is a major cause of graft loss. Renal transplant recipients have a high
      prevalence of CV risk factors that influence both patient and graft survival. We
      used data on the relationship between CV risk factors and graft and patient
      survivals to develop a discrete event simulation model to study the possible
      impact of CV risk factor reduction on transplant outcome. The simulation was
      based on a renal unit in a population that has the risk factor profile of
      patients from the West of Scotland. We studied the dynamic between patient
      numbers on the waiting list compared to the transplanted list. After establishing
      results pertinent to the renal unit, we investigated in what way potential
      changes to transplant policy affected patient numbers. These perturbations
      included changing the number of transplants performed, changing the incidence of
      acute rejection, and interventional policies where patients on the waiting list
      were selectively transplanted taking into account their CV risk factor profiles.
      Overall, the model predicts that reducing CV risk in the population with end
      stage renal failure awaiting kidney transplantation will have comparable benefits
      to foreseeable developments in immunosuppression or attainable increases in
      transplant numbers. Moreover, addressing CV risk has benefits for all patients
      regardless of whether or not they ultimately receive a kidney transplant.

PMID- 15964362
TI  - Toward the definition of immunosuppressive regimens with antitumor activity.
AB  - Immunosuppressive therapies associated with organ transplantation produce an
      increased risk of cancer development. Malignancies are increased in transplant
      recipients because of the impaired immune system. Moreover, experimental data
      point to a tumor-promoting activity of various immunosuppressive agents. In this
      study, we compared the effects of 4 immunosuppressive agents with different
      mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and
      leflunomide) on the in vitro growth of various tumor cell lines and umbilical
      vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic
      acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of
      human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and
      endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their
      growth. Our data suggest that regimens containing rapamycin, mycophenolic acid,
      or leflunomide, which have both immunosuppressive and antitumor activities,
      should be preferred in transplant recipients to minimize the risk of tumors.

PMID- 15964363
TI  - Anemia due to losartan in hypertensive renal transplant recipients without
      posttransplant erythrocytosis.
AB  - Losartan is a safe, effective long-term treatment for hypertension or
      posttransplant erythrocytosis (PTE) in renal transplant recipients. There were
      only a few studies in patients without PTE and their results were different.
      Starting from week 6 and continuing to the week 12 we observed a decrease in
      hemoglobin (Hb) and hematocrit (Hct) levels in patients without PTE. Anemia
      developed in 42.8% of the patients, and Hb levels increased after the withdrawal
      of losartan treatment. There was a significant decrease in Hct levels beginning
      from week 3 when compared with the control group. Our study suggests that
      losartan therapy can decrease Hb beyond its antihypertensive efficacy. Based on
      the capacity of losartan to decrease Hb and Hct, this drug should be carefully
      used in patients with preexistent anemia or low Hb levels.

PMID- 15964364
TI  - Correlations between leptin, body composition, bone mineral density, and bone
      metabolism in kidney transplant recipients.
AB  - INTRODUCTION: In kidney transplant recipients leptin levels are often elevated
      and bone mineral density (BMD) decreased. However, to date there are no about
      correlations between leptin and BMD in this population. It has been suggested
      that leptin is a predictor of BMD in postmenopausal women. Moreover, leptin acts
      as a marker of fat stores. We examined the relationships between leptinemia, some
      markers of nutritional status, BMD, and bone metabolism in kidney transplant
      recipients. We also assessed whether leptin was a significant and independent
      predictor of BMD in this population. METHODS: BMD and fat content (global,
      percentage, trunk) were measured using dual-energy X-ray absorptiometry in 27
      kidney allograft recipients. Markers of bone turnover and leptin were studied
      using commercially available kits. RESULTS: Leptin correlated with the percentage
      of body fat, trunk fat, lean body mass, serum creatinine, and urea. Insulin
      growth factor binding protein 1 was negatively related to waist-hip ratio and
      global and trunk fat, whereas BMD of the lumbar spine was correlated with the
      daily dose of prednisone, azathioprine, cyclosporine trough levels, serum
      calcium, as well as osteoprotegerin level. CONCLUSIONS: Leptin levels are
      associated with graft function and body fat in kidney allograft recipients.
      Leptin is not related to nutritional status, BMD, or bone metabolism in kidney
      allograft recipients, but is associated with the current dosage of
      immunosuppressants and the serum calcium.

PMID- 15964365
TI  - Study of surgical complications between primary and secondary renal transplants.
AB  - INTRODUCTION: In a retrospective study we reviewed the surgical complications of
      primary and secondary renal transplants in 1108 consecutive renal transplants.
      PATIENTS AND METHODS: Between 1992 and 2001, 1108 consecutive renal transplants
      were performed using living related and unrelated donors. Sixty-five second
      grafts (group 1) were performed in patients of mean age 34.5 (range 18 to 55) and
      1043 primary renal transplants (group 2) in patients of mean age 38.2 (range 10
      to 63). One case in group 1 and 94 cases in group 2 were diabetic patients.
      Factors analyzed were vascular, wound, ureteral, and lymphocele complications.
      RESULTS: The follow-up period ranged from 10 to 120 months (average 27.3). The
      mean creatinine level in patients with active grafts was 1.45 mg/dL. The last
      creatinine levels in the two groups were not significantly different. The rates
      of surgical complications were 4.6% in group 1 and 3.8% in group 2, including
      vascular complications (one case in group 1 and 16 in group 2), wound problems
      (nobody in group 1 and seven cases in group 2), lymphocele (two cases in group 1
      and eight cases in group 2), and ureteral complications (nobody in group 1 and
      nine cases in group 2). The incidence of complications between the two groups did
      not show a significant difference (P = .72). CONCLUSION: With some changes in the
      standard operation, surgical complications in second renal transplants are not
      more frequent than among the primary transplants. Therefore, we strongly
      recommend a second renal transplant when the primary graft has failed.

PMID- 15964366
TI  - Orthotopic liver transplantation with vena cava preservation in cirrhotic
      patients: is systematic temporary portacaval anastomosis a justified procedure?
AB  - INTRODUCTION: We evaluated the peri- and postoperative effects of the lack of a
      temporary portocaval anastomosis (TPCA) during orthotopic liver transplantation
      (OLT) in 84 patients with cirrhosis. PATIENTS AND METHODS: From December 1996 to
      December 2002, 156 liver transplant recipients included (54%; 60 men and 24
      women) of mean age 52 +/- 9 years with portal hypertension. In whom peri- and
      postoperative data were analyzed. RESULTS: The median fall in mean arterial
      pressure upon vascular clamping and unclampings was 20 mm Hg (range 15 to 75),
      while the median duration of portal vein clamping was 77 minutes. The median
      amount of blood autotransfusion was 1100 mL (range 0 to 5400). The median number
      of red blood cell and fresh-frozen plasma units transfused were 5 and 6.5,
      respectively. The median intraoperative urinary output was 72 mL/h (range 11 to
      221). Three patients (3.5%) presented a perioperative complication, but no
      perioperative death was observed. Six patients experienced an early postoperative
      complication (<10 days): five hemodynamic complications and one transient renal
      failure, which did not require hemodialysis. One patient (1%) died at 12 hours
      after OLT from acute pulmonary edema. CONCLUSION: This study shows that
      systematic TPCA during OLT with preservation of the native retrohepatic vena cava
      in cirrhotic patients does not appear to be justified. In contrast, peri- and
      postoperative hemodynamic parameters as well as blood component requirements were
      comparable to those of the literature reporting OLT with straightforward TPCA.

PMID- 15964367
TI  - Liver transplant with portocaval hemitransposition: blood supply with only
      hepatic artery is possible?
AB  - We present herein a case of orthotopic liver transplantation (OLT) with
      portocaval hemitransposition. The patient underwent OLT for hepatocellular
      carcinoma with diffused portomesenteric vein thrombosis. The unique feature of
      this case was that 6 months after the operation, because of recurrent carcinoma,
      the hepatic vein was occluded and the portal vein became the drainage vein and
      the hepatic artery was the only vessel that supplied the liver. Yet the patient
      survived. Regarding the unique hemodynamic changes of the patient, could we let
      the portal vein alone in case of diffuse portomesenteric thrombosis in OLT?

PMID- 15964368
TI  - Relation between the middle hepatic vein drainage area volume and alanine
      aminotransferease after left liver harvesting.
AB  - Complete outflow is impossible to maintain on both sides in donors undergoing
      hemiliver graft harvesting, because the middle hepatic vein (MHV) can be
      preserved on only one side. The area in which outflow veins are disrupted becomes
      congested and does not sufficiently regenerate. The relation between changes in
      alanine aminotransferase (ALT) and the congestive area volume of the congestive
      area is unknown. The 64 subjects presented herein were living donors who provided
      the left liver with the caudate lobe and MHV trunk. The midpoint between the
      tributaries of the MHV and the right hepatic vein was determined preoperatively
      using computed tomography. The midpoint between the tributaries of the MHV and
      right hepatic vein and the borderline between the right and left liver were used
      to predict the MHV drainage area volume. ALT was measured in donors on
      postoperative days 1, 3, 5, 7, 10, and 14. The patients were divided into three
      groups according to the ratio of calculated MHV drainage area volume in the
      remnant right liver: less than 15% (n = 21, group A); greater than 15% and less
      than 20% (n = 18, group B); greater than 20% (n = 25, group C). There were
      significant differences in the ALT levels between groups (P = .004). MHV drainage
      area volume, calculated using the present method, was associated with high ALT
      levels after left liver harvesting with the MHV. The present study suggests that
      persistently high ALT levels are associated with the volume of the interrupted
      MHV drainage area.

PMID- 15964369
TI  - What is the best immunosuppression in living donor liver transplantation?
AB  - INTRODUCTION: As we have learned, there are no golden rules of immunosuppression
      in solid organ transplantation, and every transplant program is using its own
      regimen to prevent or treat rejection. We have retrospectively analyzed the
      incidence and severity of acute rejection in a consecutive series of living donor
      liver transplants. The major objective during the whole study period was to
      ultimately avoid any steroids from the beginning. METHODS: Twenty one adult
      patients and five children received 23 right, one left, and two left lateral lobe
      grafts from genetically or emotionally related living donors, including four ABO
      incompatible pairs. The majority of patients had triple initial
      immunosuppression, based on tacrolimus, mycophenolate mofetil or sirolimus, and
      basiliximab or daclizumab. Except methylprednisolone administered before
      reperfusion in 13 patients, only seven had prednisolone after transplantation,
      and 12/26 had a completely steroid-free regimen. RESULTS: The overall incidence
      of biopsy-proven acute rejection was 4/21 in adults (19%) and 4/5 in children
      (80%). Rejections were mild in five and moderate in three cases, respectively,
      and easily reversed with steroids in all patients. Different combinations of
      immunosuppressive drugs or ABO incompatibility did not seem to have an influence
      on the risk of rejection. CONCLUSION: Despite the small number of patients in
      this series, completely steroid-free triple-drug immunosuppression with
      tacrolimus, mycophenolate mofetil, and basiliximab is safe and efficient to
      prevent acute rejection in adult recipients of living donor liver transplants. At
      least short-term administration of prednisolone should be considered in pediatric
      patients.

PMID- 15964370
TI  - Mortality while awaiting liver retransplantation: predictability of MELD scores.
AB  - INTRODUCTION: Model for End-stage Liver Disease (MELD) scores at the time of
      listing on the transplant waiting list have been shown to accurately predict 3
      month mortality in adults. There is no data assessing the accuracy of the MELD
      scores in predicting mortality of patients awaiting liver retransplantation. We
      sought to determine the outcome of patients listed for retransplantation at a
      single center and the accuracy of MELD scores in predicting mortality on the
      transplant waiting list. METHODS: A retrospective review of adult patients at a
      single center listed for a second liver transplantation during the years 1993 to
      2000. MELD scores and a concordance statistic were calculated at the time of
      initial listing and initial transplant as well as the time of relisting for a
      second transplant and at 2, 4, 6, 8, 12, and 24 weeks after relisting. RESULTS:
      Of the 63 patients in the study, 43 (68%) received a second transplant, and 20
      (32%) died while awaiting retransplantation. Of the patients receiving a second
      transplant, 13 (30%) died within 1 year of receiving the transplant. The most
      common cause of death on the waiting list was sepsis (50%), hepatorenal syndrome
      (20%), and multiorgan failure (10%), whereas the majority of deaths
      posttransplantation were sepsis-related (69%). At the time of relisting the c
      statistic for MELD scores predicting death after 1 week on the waiting list was
      0.78 (P = .007). After 3 months on the waiting list, the c-stat was largely
      unchanged (0.76, P = .04). CONCLUSIONS: We have shown that MELD scores may
      predict mortality on the transplant waiting list for patients listed for a second
      transplant.

PMID- 15964371
TI  - MELD scores do not predict patient morbidity while on the liver transplant
      waiting list.
AB  - The goals of this study were to assess waitlist morbidity in terms of the
      frequency of health care services utilized by patients while on the liver
      transplant (LTX) waiting list and to determine whether that utilization can be
      predicted by the Model for End-Stage Liver Disease (MELD). Sixty-three
      noncomatose subjects were followed from waitlist placement until death, change in
      status, LTX, or study discontinuance. Health care events included doctor/clinic
      visits, labs, outpatient/inpatient tests and procedures, and hospital/intensive
      care unit days. Listing MELD scores and LTX MELD scores were examined against the
      number of health care event occurrences within 60 days of listing and 60 days of
      LTX, respectively, as were changes in MELD scores between listing and LTX and
      differences in the number of occurrences between the two time points. The only
      significant correlations noted were between LTX MELD scores and number of
      hospital days near LTX (r = .360, P = .046) and between LTX MELD scores and the
      sum total number of occurrences near LTX (r = .370, P = .044). These results
      suggest that MELD scores do not appear to predict morbidity in terms of health
      care utilization in patients awaiting LTX. Developing a system capable of
      predicting waitlist morbidity may lead to the implementation of medical
      interventions aimed at circumventing foreseeable complications and/or crises in
      patients awaiting LTX.

PMID- 15964372
TI  - Treatment of steroid-resistant acute liver transplant rejection with basiliximab.
AB  - Current rescue therapies for acute steroid-resistant rejection, such as OKT3 and
      high-dose tacrolimus, are not uncommonly associated with side effects that
      contribute to significant morbidity of the patient. Basiliximab is a chimeric
      monoclonal antibody that acts as an interleukin-2 receptor antagonist on the
      surface of activated T lymphocytes. It has until now only been used as
      immunoprophylaxis in adult liver transplant patients. In this report, we describe
      the use of Basiliximab as rescue therapy in a case of acute steroid-resistant
      rejection in an adult living related liver transplant recipient.

PMID- 15964373
TI  - Orthotopic liver transplantation for incurable alveolar echinococcosis: report of
      five cases from west China.
AB  - Alveolar echinococcosis of the liver, caused by the larval stage of Echinococcus
      multilocularis, has the characteristics of a slow-growing liver cancer. The aim
      of the present work was to report a series of patients who received orthotopic
      liver transplantation (OLT) for life-threatening disease. Our article summarizes
      the medical history, diagnosis, treatment, and prognosis of five patients who
      received OLT between 2001 and 2002. Most patients had a long history of
      symptomatic disease (iterative cholangitis, obstructive jaundice) and repeated
      abdominal surgery. One patient died during the hospitalization mostly related to
      bacterial infection and multiple organ failure. Another accidental death happened
      3 months later from heart failure. Three patients are alive in good condition
      verifying that OLT is a feasible option for these end-stage cases. In general,
      combination therapy-chemotherapy, interventional therapy, radical surgery or/and
      OLT at an early stage-is proposed in advanced cases of which OLT has clearly
      played a vital role. Despite major technical difficulties, OLT for incurable
      disease is feasible. Specific management is needed to improve the results:
      earlier decision for OLT in symptomatic disease, routine pre- and post-transplant
      therapy, reduced immunosuppression, and regular follow-up.

PMID- 15964374
TI  - Successful use of sirolimus in a patient with bulky ovarian metastasis of
      hepatocellular carcinoma after liver transplantation.
AB  - This 44-year-old woman developed multifocal hepatocellular carcinoma (HCC) within
      hepatitis B-induced liver cirrhosis. At the time of listing for transplantation
      the HCC had progressed beyond the Milan criteria. Due to her young age, high
      grade of histological differentiation according to biopsy, and lack of
      therapeutic alternatives, she was listed for transplantation. She received an
      organ from the Eurotransplant marginal liver list. Immunosuppression was reduced
      to tacrolimus monotherapy within 4 months. Five months after transplantation
      bilateral bulky ovarian metastases were seen on computed tomography (CT) scan. A
      bilateral salphingo-oophorectomy was performed and immunosuppression switched to
      sirolimus monotherapy. Fourteen months after this procedure and 19 months after
      transplantation, the patient is asymptomatic with stable liver function. She is
      free of recurrence as judged by CT scan, bone scan, and alpha-fetoprotein. In
      conclusion, radical surgical treatment and immunosuppression using sirolimus may
      achieve tumor-free survival in selected patients with advanced or recurrent HCC.

PMID- 15964375
TI  - Successful treatment of liver transplant-associated Kaposi's sarcoma with long
      term vincristine.
AB  - Kaposi's sarcoma has a higher incidence in organ transplant recipients. We report
      on a 41-year-old Turkish man with liver transplantation-associated Kaposi's
      sarcoma that involved the skin and the gut. Immediately after discontinuation of
      immunosuppressive medication, there was an acute rejection episode. After
      controlling the acute rejection with steroids, the immunosuppressive treatment
      was continued together with vincristine, which resulted in disease remission.
      After 6 months, withdrawal of vincristine lead to relapse of the disease,
      prompting commencement of vincristine again, which has maintained the patient in
      remission for more than 3 years without any significant side effects. In
      conclusion, long-term vincristine may be an effective, safe treatment option for
      Kaposi's sarcoma.

PMID- 15964376
TI  - Ki-67 proliferation index in Kaposi's sarcoma after renal transplantation:
      findings in skin-only cases versus cases with internal-organ involvement.
AB  - Kaposi's sarcoma (KS) is an angioproliferative condition that accounts for 6% of
      all malignancies in organ transplant patients. When we review the literature, the
      results of the studies comparing the different stages and the proliferative
      activity of the tumor are challenging. However, we found no previous study on Ki
      67 protein expression in KS that correlates skin and organ lesions. In the
      current study, we investigated whether there is a correlation on the
      proliferative activity between skin and internal organ lesions in KS.
      Proliferative activity of 13 biopsy specimens of KS was assessed
      immunohistochemically using the monoclonal antibody MIB-1 (Ki-67). Mann-Whitney U
      test is used for statistical analysis and a P value < .05 was considered
      significant. Seven of 13 cases were skin and six were internal organ KS. For skin
      lesions, the mean MIB-1 proliferation index was 14.5%, and it was 13% for organ
      lesions. There was no significant association between skin and internal organ KS
      in regard to MIB-1 PI (P > .05). The findings suggested that the proliferative
      activity in KS does not differ in skin and organ lesions. On the other hand, it
      should be considered that the number of cases in our study was limited and
      further studies with a larger series are needed.

PMID- 15964377
TI  - Hepatic angiosarcoma and liver transplantation: case report and literature
      review.
AB  - Hepatic angiosarcoma is a rare malignant vascular tumor that accounts for up to
      2% of all primary liver tumors. Accurate diagnosis of this tumor is difficult,
      especially if the patient has no history of exposure to specific carcinogens
      including thorotrast, arsenicals, and vinyl chloride monomer. Diagnosis of
      diffuse angiosarcoma by means of liver biopsy has been reported as treacherous
      and nondiagnostic. Herein, we present a case of a 61-year-old Caucasian male with
      history of cryptogenic cirrhosis, normal alpha-fetoprotein, and pretransplant
      abnormal liver MRI who underwent nondiagnostic liver biopsies followed by liver
      transplantation. High grade diffuse angiosarcoma was diagnosed in the explanted
      liver. The patient developed bone metastases at 8 months and is alive 1 year
      posttransplantation. Diffuse liver tissue infiltration seen pretransplant on CT
      scan or MRI, suggesting the possibility of diffuse liver lesions (HCC,
      angiosarcoma, etc) must be fully investigated with all techniques available
      including multiple open liver biopsies to avoid the sacrifice of a liver
      allograft in these patients.

PMID- 15964378
TI  - Is hepatitis B immunoglobulin prophylaxis needed for liver transplantation in the
      era of new antivirals?
AB  - Chronic infection with hepatitis B virus (HBV) is one of the most common causes
      of cirrhosis of the liver and hepatocellular carcinoma worldwide, frequently
      requiring liver transplantation. Other nonliver organ transplants get infected de
      novo or through reactivation from previous active or inactive infections. With
      significant improvements in the surgical techniques and immunosuppressive
      regimens over the last 20 years, organ transplantation has become the most
      effective and lifesaving therapy for patients with chronic renal failure,
      cirrhosis, hepatocarcinoma, and heart failure. Until recently chronic HBV
      infection was considered a formal contraindication for liver transplantation,
      since recurrence of infection without prophylaxis occurs in 75% to 90% of the
      patients, with significant morbidity and mortality and few therapeutic
      alternatives. However, the introduction of hepatitis B immunoglobulin (HBIG) a
      decade ago to reduce the risk of reinfection of liver grafts, and more recently
      the availability of nucleoside analogues with few side effects and easy
      administration, have led to a dramatic improvement in patient outcomes with a
      risk of long-term HBV reinfection of less than 10% with combined HBIG and
      lamivudine prophylaxis. Chronic HBV infection in kidney, heart, and other organs
      has become a serious long-term problem and one of the most frequent and important
      comorbidities affecting graft and patient survival. Fortunately the introduction
      of nucleoside analogues allows significant control of viral replication and
      prevents progression of liver disease and other organ damage. In the present
      article we discuss the current indications for HBV prophylaxis and treatment
      prior to and after organ transplantation, as well as the most cost-effective way
      to apply different regimens to reduce side effects and improve survival and
      quality of life after transplantation.

PMID- 15964379
TI  - De novo hepatocellular carcinoma in a liver allograft associated with recurrent
      hepatitis B.
AB  - Recurrent hepatocellular carcinoma is well described following liver
      transplantation. However, de novo hepatocellular carcinoma in the allograft is
      rare. We describe the clinical and pathological features of a case of de novo
      hepatocellular carcinoma arising in a cirrhotic allograft 9 years following
      transplantation for chronic hepatitis B.

PMID- 15964380
TI  - Peginterferon and ribavirin in patients with HCV cirrhosis after liver
      transplantation.
AB  - The objective of the study was to assess the efficacy of antiviral therapy in
      patients with hepatitis C virus (HCV) recurrence after liver transplantation
      (OLT). We included 30 patients of mean age 56 years, who experienced HCV
      recurrence after OLT. Mean time from OLT to the beginning of therapy was 57
      months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21),
      cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously
      been diagnosed with allograft HCV cirrhosis. Patients were treated with
      peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48
      (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20
      months, two patients had died due to biliary sepsis (while on therapy) and acute
      myocardial infarction (7 months after the end of therapy). End of treatment
      virological response was achieved in 19 patients (63.3%) and sustained
      virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic
      patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P =
      .732). Every patient had some adverse event; in 11 patients (36.7%) it was
      withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the
      starting dose was decreased (40%). There were neither rejection episodes nor
      cirrhotic complications during therapy, but infections were more common in
      cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients
      the sustained virological response to combined antiviral therapy was similar to
      that in noncirrhotic patients, but severe adverse events including infections
      were much more common.

PMID- 15964381
TI  - Preoperative dobutamine stress echocardiography, intraoperative events, and
      intraoperative myocardial injury in liver transplantation.
AB  - INTRODUCTION: The appropriate method of screening for coronary artery disease in
      patients who present for liver transplantation is currently uncertain. METHODS:
      We assessed the utility of a screening protocol using dobutamine stress
      echocardiography (DSE) in 119 patients who underwent liver transplantation.
      Patients with cardiac risk factors had DSE performed, and those with positive
      results were referred for coronary angiography. Outcome was myocardial injury
      during liver transplantation determined by an elevation of cardiac troponin T
      measured after transplantation. RESULTS: Seventy-three patients had DSE
      performed; eight were reported as positive for inducible ischemia. Seven of these
      patients underwent coronary angiography, and one had significant coronary artery
      disease. Postoperative troponin elevation occurred in 14 patients. There was no
      significant difference in the prevalence of troponin elevation in those patients
      with positive DSE versus those with negative DSE. No significant difference was
      identified in the prevalence of troponin elevation when comparing those patients
      with cardiac risk factors who underwent DSE with those patients with no risk
      factors and no DSE performed. DSE had a sensitivity of 0.2 and a specificity of
      0.9 for myocardial injury. The prevalence of intraoperative hemodynamic
      instability was significantly higher in patients who had evidence of myocardial
      injury, but hemodynamic instability was no more common in patients who had a
      positive DSE. CONCLUSION: When used in accordance with our protocol a positive
      DSE does not reliably identify patients at high cardiac risk during liver
      transplantation, but a negative DSE is strongly predictive of no myocardial
      injury.

PMID- 15964382
TI  - Liver transplantation for familial amyloid polyneuropathy non-VAL30MET variants:
      are cardiac complications influenced by prophylactic pacing and immunosuppressive
      weaning?
AB  - BACKGROUND: Cardiac complications represent a cause of morbidity and mortality
      after liver transplantation among patients with familial amyloid polyneuropathy
      (FAP), especially for the non-VAL30MET variant types. METHODS: We retrospectively
      evaluated 11 recipients from a nonendemic area including 90.9% affected by FAP
      variants. Preoperative cardiovascular symptoms were present in 81% of patients.
      An intraoperative pacemaker was placed prophylactically in 90.9% of all
      recipients. Since tacrolimus has been reported in the international literature to
      display cardiac toxicity, we evaluated the influence of intraoperative
      prophylactic pacing and rapid postoperative weaning from tacrolimus, mainly
      allowed by thymoglobulin on the occurrence of posttransplantation cardiac
      complications. RESULTS: One patient received a combined heart-liver transplant,
      another, living donor liver transplantation. We did not observe any significant
      intraoperative cardiac complications. Postoperatively, the pacemaker was removed
      from all patients but 1. Five patients received tacrolimus and steroids; a
      subsequent, second group of 6 patients (54.5%) was treated with thymoglobulin
      followed by tacrolimus. At discharge the mean tacrolimus level was 10.6 ng/mL,
      whereas after 1 month it was 7.5 ng/mL. We observed a case of acute cellular
      rejection before discharge, which was successfully treated with intravenous
      steroids and OKT3. After a mean follow-up of 17.4 months (range, 1-31), 2
      patients had died (18.1%): 1 due to sepsis and another, to MI. Two recipients
      experienced cardiac complications (18.1%), namely, the patient who died due to an
      myocardial infarction and a second one with a tachyarrhythmia, which was treated
      successfully with beta-blockers and amiodarone. CONCLUSION: Prophylactic pacing
      and rapid weaning from immunosuppression are still associated with a significant
      rate of postoperative cardiac complications.

PMID- 15964383
TI  - Clinicopathological review of 18 cases of liver allografts lost due to bile duct
      necrosis.
AB  - Clinical, radiographic, and pathological features of 18 patients with biliary
      necrosis in their explanted liver allografts were reviewed. Twelve patients were
      men and ages ranged from 27 to 72 years. Indications for initial liver transplant
      (LT) were viral hepatitis (n = 7), steatohepatitic cirrhosis (n = 3), cryptogenic
      cirrhosis (n = 3), secondary sclerosing cholangitis (n = 2), primary sclerosing
      cholangitis (n = 1), biliary atresia (n = 1), and nodular regenerative
      hyperplasia (n = 1). Donor age ranged from 16 to 75 years. Duct-to-duct biliary
      anastomoses were fashioned in 13 cases; warm and cold ischemia times were not
      significantly different from general LT population. Seventeen allograft biopsies
      after recirculation had no significant findings. Post-LT, clinical and
      radiographic evaluation indicated biliary strictures (n = 7), bile leak (n = 7),
      intrahepatic abscess (n = 1), and duodenal perforation (n = 1). Radiographic
      vascular studies suggested hepatic arterial thrombosis or stenosis in 11 cases.
      Biopsies prior to retransplantation were performed on 17 patients and showed
      acute rejection (n = 10), biliary outflow impairment (n = 4), normal histology (n
      = 2), and centrilobular necrosis (n = 1). Retransplantation was performed 14 to
      334 days after initial LT. Pathological examination of explants revealed
      perihilar duct necrosis in all cases, with bacterial colonies (n = 10) and fungal
      organisms (n = 2). Arterial thrombi were seen in 10 cases, and two had prominent
      arteriosclerosis. Infarction and centrilobular necrosis were seen in 9 and 13
      cases, respectively. Four explants showed features of biliary outflow impairment.
      Twelve patients were alive 6 to 18 months following retransplantation. We
      conclude that post-LT biliary necrosis is associated with ischemia, and such a
      complication is rarely evident in allograft biopsies. Biliary and vascular
      imaging studies are essential in evaluating patients for this complication.

PMID- 15964384
TI  - Liver failure in transplanted liver due to Amanita falloides.
AB  - Two patients underwent liver transplantation due to Amanita falloides poisoning.
      In one of them the clinical symptoms, signs, and laboratory findings related to
      liver failure were similar to the findings before the transplantation. The
      patient died and the pathological examination of the liver was similar to the
      patient's earlier explanted liver.

PMID- 15964385
TI  - Factors in association with sepsis after liver transplantation: the Hungarian
      experience.
AB  - Sepsis is the major cause of patient death after orthotopic liver transplantation
      (OLT). To identify risk factors for sepsis, we analyzed all 199 primary OLTs
      performed between 1995 and 2004. Patients were divided into 2 groups according to
      whether they experienced sepsis after liver transplantation. Recipient,
      perioperative factors, and complications were subjected to univariate analyses.
      Statistically significant factors were exposed to multivariate analyses: Cox
      regression and Hosmer-Lemeshow test. Sepsis occurred in 45 (23%) patients.
      Recipient Child-Pugh score, preoperative broad spectrum antibiotic (meropenem)
      prophylaxis, intraoperative red blood cell transfusion, starch infusion,
      postoperative bleeding, hepatic artery thrombosis, and biliary leakage/necrosis
      were independent risk factors for sepsis. Our results agree with the
      international experience. A high amount of starch infusion and an extended use of
      broad spectrum antibiotics for prophylaxis adverse experiences in our center and
      have been removed from the protocol.

PMID- 15964386
TI  - De novo immunosuppression with sirolimus and tacrolimus in heart transplant
      recipients compared with cyclosporine and mycophenolate mofetil: a one-year
      follow-up analysis.
AB  - BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in
      combination with a calcineurin inhibitor in heart transplant recipients. METHODS:
      From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment
      group) received a combination of sirolimus, tacrolimus, low-dose rabbit
      antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial
      survival, rate of rejection, incidence of infection, probability of developing
      diabetes mellitus, renal function, platelet and white blood cell counts, and
      incidence of coronary artery disease at 1 year, were compared with a cohort of 25
      patients (control group) who underwent transplantation primarily in 2000 and in
      early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids.
      All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier
      actuarial 1-year survival rates were equivalent between groups (97% for the
      treatment group and 88% for the control group), as was freedom from allograft
      rejection (48% and 42% for treatment and control groups, respectively). No cases
      of transplant arteriopathy were noted within the first posttransplantation year.
      Renal function was not significantly affected in either group. There was a
      striking increased incidence of mediastinitis in the treatment group (19%) versus
      0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated
      with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well
      (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose
      rabbit antithymocyte globulin) were associated with an increased incidence of
      mediastinitis and posttransplantation diabetes mellitus. No obvious long-term
      benefit on survival, arteriopathy, or renal function was noted.

PMID- 15964387
TI  - Therapeutic mycophenolic acid monitoring by means of limited sampling strategy in
      orthotopic heart transplant patients.
AB  - Therapeutic drug monitoring (TDM) is essential to maintain the efficacy of many
      immunosuppressant drugs while minimizing their toxicity. TDM of mycophenolate
      mofetil requires area under the curve AUC determinations but appears laborious,
      costly, and clinically impractical. To overcome these problems, limited sampling
      strategies (LSS) have been proposed in adult and pediatric renal transplant
      patients. The purpose of this study was to develop an LSS in heart transplant
      patients. Forty-four mycophenolic acid (MPA) full AUC(0-12h) profiles were
      generated by high-performance liquid chromatography in nine heart transplant
      patients during the first 12 weeks posttransplant. Each patient received
      concomitant cyclosporine and prednisone therapy. Multiple stepwise regression
      analysis was used to define the time points of MPA levels to explain the MPA
      AUC(0-12h). Agreement between abbreviated AUC and the full AUC(0-12h) was tested
      by means of a Bland and Altman analysis. The highest coefficient of determination
      r(2) among MPA AUC and single concentrations (r(2) = .610) was observed with
      C(2), while C(12) provided the lowest one (r(2) = .003). Stepwise linear
      regression showed that the minimal model with the best estimation of MPA AUC(0
      12h) was obtained at timed values of 1.25, 2, and 6 hours. The corresponding
      estimated model was AUC = 5.568 + 0.902 * C(1.25) + 2.022 * C(2) + 4.594 * C(6)
      (r(2) = .926). Bland and Altman analysis revealed good agreement between
      predicted AUC and full AUC. A further interesting model equation obtained by four
      samples was AUC = 3.800 + 1.015 * C(1.25) + 1.819 * C(2) + 1.566 * C(4) + 3.479 *
      C(6) (r(2) = .948).

PMID- 15964388
TI  - Impact of cardiac transplantation in 24 hours circadian blood pressure and heart
      rate profile.
AB  - OBJECTIVE: The aim of the present study was to evaluate 24 hours blood pressure
      (BP) and heart rate changes as well as 24-hour circadian BP rhythm of cardiac
      transplant recipients. METHODS: Twenty-five transplant recipients and twenty-five
      healthy volunteers underwent 24-hour ambulatory BP monitoring. Parameters of 24
      hour ambulatory BP monitoring (24-h/daytime/nightime systolic, diastolic BP,
      pulse pressure, and heart rate) were determined in all patients. RESULTS: Clinic
      systolic/diastolic BP, mean 24-h systolic/diastolic BP, mean daytime
      systolic/diastolic BP, mean nighttime systolic/diastolic BP, and mean 24
      h/daytime/nighttime heart rate were significantly higher in transplant recipients
      than in control group subjects. Standard deviations of 24-h/daytime/nighttime
      heart rates were significantly lower in transplant recipients. Dippers were 48%
      of the control and only 12% of the transplantation group. CONCLUSIONS: Cardiac
      transplant recipients had increased ambulatory BP. They also had increased 24
      h/daytime/nighttime heart rate and decreased heart rate variability. Also,
      diminished nocturnal decrease of BP was found in transplant recipients.

PMID- 15964389
TI  - Donor CCR5 Delta32 polymorphism and outcome following cardiac transplantation.
AB  - BACKGROUND: Chemokines regulate the recruitment and trafficking of leukocytes
      during an immune response. Animal models have shown correlations between
      chemokine production and leukocyte infiltration during allograft rejection. Also,
      antagonism of chemokine receptors in transplant models has produced prolonged
      graft survival. Individuals homozygous for a 32 base pair deletion in the CC
      chemokine receptor 5 (CCR5) gene have an inactive receptor. Renal transplant
      recipients homozygous for the deletion have been shown to survive significantly
      longer than those heterozygous or homozygous for the wild type allele. CCR5
      ligands are upregulated during allograft rejection aiding infiltration of
      leukocytes. We investigated the influence of CCR5Delta32 polymorphism on outcome
      following human cardiac transplantation. METHODS: Recipients and corresponding
      donors were genotyped for CCR5Delta32 polymorphism using polymerase chain
      reactions. RESULTS: We found no correlation between recipient genotype and
      outcome following transplantation. However, there was a significant correlation
      between donor genotype and mortality in patients transplanted for a nonischemic
      condition (DD = n/a, ID = 4%, II = 25%, P = .0014). CONCLUSIONS: The induction of
      CCR5 expression in endomyocardial biopsy tissue is known to correlate with
      leukocyte graft infiltration. We suggest that donor CCR5 may be more important
      for leukocyte trafficking during rejection than recipient CCR5 expression. The
      CCR5 gene is highly conserved, and due to the small population available for this
      study, more work is required from other centers.

PMID- 15964390
TI  - Liver transplant combined with heart transplant in severe heterozygous
      hypercholesterolemia: report of the first case and review of the literature.
AB  - Familial hypercholesterolemia (FH) is a dominant inherited disease of low-density
      lipoprotein (LDL) metabolism caused by mutations of LDL receptors mainly located
      in the liver. This metabolic disorder is responsible for severe cardiovascular
      disease, from coronary lesions to chronic heart failure (CHF). Liver
      transplantation in homozygous FH provides the missing functional LDL receptors
      and thus partially restores LDL receptor activity to more than 50% of normal.
      Combined heart and liver transplantation was successfully performed in a
      homozygous FH patient with end-stage heart failure. Herein we report our
      experience with a heterozygous male patient with terminal CHF, and review data
      from the literature on short- and long-term results of such procedures.

PMID- 15964391
TI  - Successful heart transplantation after 13 hours of donor heart ischemia with the
      use of HTK solution: a case report.
AB  - INTRODUCTION: For heart transplantation (HTx), the recommended ischemic time (IT)
      for donor heart is not to exceed 6 hours. Though Dr Christiaan Barnard used a
      donor heart with IT of 16 hours, 50 minutes with a portable hypothermic perfusion
      system in 1981, the recorded IT of donor hearts reported recently is 8 hours,
      with no adverse effects. CASE REPORT: The patient, a 14-year-old boy of blood
      type O, was diagnosed with cardiomyopathy at age 12. In early September 2003, the
      patient was recommended for HTx. His condition deteriorated 18 days later with
      low CO, elevated pulmonary vascular resistance, and frequent ventricular
      tachycardia, further complicated by pneumonia and multiorganism infections, which
      were contraindications for HTx. On September 22, 2003, a donor heart of blood
      type O was available 370 km away. Another patient of blood type B with severe
      heart failure was matched for the HTx. During the intervening time, another donor
      heart of blood type B became available locally. We matched the type B donor heart
      to the type B recipient. Since the type O donor heart seemed to be wasted, we
      performed HTx for the boy. Though preserved for 12 hours in cold cardioplegia,
      the donor heart was implanted with biatrial anastomosis that took 1 hour. The
      total IT of this donor heart was 13 hours. The recipient recovered and was
      discharged 3 months later. CONCLUSIONS: The IT of 13 hours for this donor heart
      is believed to be a world record. Our experience demonstrates that preservation
      time of donor heart may exceed 6 hours.

PMID- 15964392
TI  - The frequency of interleukin-10- and interleukin-5-secreting CD4+ T cells
      correlates to tolerance of transplanted lung.
AB  - Posttransplant bronchiolitis obliterans syndrome (BOS) results from a chronic
      immunological/inflammatory insult that leads to fibro-obliteration of the lumen
      of the allograft airways. The functional T-cell response that is associated with
      graft acceptance needs to be further clarified in humans. The aim of the present
      study was to assess the functional activity of peripheral CD4+ T lymphocytes in
      nine lung transplant recipients with BOS stage II or III (mean 5.4 years after
      transplant), in seven lung patients with stable clinical conditions (3.4 years
      posttransplant); and in six normal controls. Peripheral CD4+ T cells, obtained by
      magnetic bead vs negative purification, were studied using a computer-assisted
      enzyme-linked immunospot assay (ELISPOT) to assess the number of IFN-gamma-,
      interleukin (IL)5-, and IL10-gamma-producing cells (no./10(6) CD4+ cells) after
      allogeneic stimulation. The frequencies of IFN-gamma-producing CD4+ cells did not
      change significantly in stable patients compared to those with BOS. Interestingly
      in BOS, the number of IL5- and IL10-producing cells was significantly lower than
      in stable patients (P < or = .05), suggesting a possible role of these Th2
      cytokines in the modulation of graft tolerance.

PMID- 15964393
TI  - CD4-veCD8-ve CD30+ve T cells are detectable in human lung transplant patients and
      their proportion of the lymphocyte population after in vitro stimulation with
      donor spleen cells correlates with preservation of lung physiology.
AB  - INTRODUCTION: Survival following lung transplantation is less than 50% at 5
      years, mainly due to immune-mediated chronic rejection. Recently a novel subset
      of T cells, CD4-veCD8-ve CD30+ve, so-called double negative (DN) CD30+ve T cells,
      has been described and shown to be responsible for tolerance in an animal model
      of skin transplantation. METHODS: We investigated 18 lung transplant recipients
      for the presence of DN CD30+ve T cells in resting peripheral blood and also
      following in vitro stimulation of recipient peripheral blood mononuclear cells
      (PBMCs) with donor spleen cells. RESULTS: Small percentages (0.2% to 6%) of DN T
      cells are detectable in resting PBMCs of human transplant patients (n = 18), but
      these did not correlate with allograft function, acute rejection episodes, HLA
      mismatch, or CMV status. On repeated stimulation of recipient PBMCs (two
      exposures) in vitro by donor spleen cells (2:1 ratio stimulators to responders)
      the percentage of DN CD30+ve T cells within the lymphocyte pool correlated with
      preservation of allograft lung function (both for FEV(1), P = .009, and FEF(25
      75), P = .036) and was inversely correlated with grade of chronic rejection. On
      repeated exposure of recipient PBMCs to donor spleen cells with a 1:1 ratio the
      percentage of DN CD30+ve T cells correlated with the number of acute rejection
      episodes of grade 2 or greater. The total number of HLA mismatches correlated
      with the percentage DN CD30+ve T cells present after primary stimulation of
      recipient PBMCs with donor spleen cells (1:1 ratio). The number of mismatches at
      the B locus inversely correlated with the percentage of DN CD30+ve T cells after
      primary stimulation of recipient PBMCs with donor spleen cells (1:1 ratio; P =
      .031, n = 18). CONCLUSION: Percentages of DN CD30+ve T cells present following
      repeated stimulation of recipient PBMCs by donor spleen cells correlated with
      preservation of graft function following lung transplantation.

PMID- 15964395
TI  - A more persistent tolerance to islet allografts through bone marrow
      transplantation in minimal nonmyeloablative conditioning therapy.
AB  - INTRODUCTION: Islet transplantation is a therapeutic approach to prevent diabetes
      complications. However, the side effects of the required lifelong
      immunosuppressive regimens to prevent graft rejection restrict the impact of type
      1 diabetes. One strategy to overcome these limitations is tolerance induction and
      graft acceptance through hematopoietic chimerism. In this study we investigated
      whether tolerance to major histocompatibility complex (MHC) and minor-disparate
      islet allografts could be induced by minimal nonmyeloablative conditioning and
      whether more persistent donor-specific islet allografts were accepted if the
      grafts were implanted with simultaneous bone marrow cells. METHODS: The donor and
      recipient mice were BALB/c(H-2(b)) and C57BL/6(H-2(d)), respectively. In group 1
      streptozotocin-induced diabetic C57BL/6(H-2(d)) mice received only 500 islets of
      BALB/c(H-2(b)). Group 2 recipients conditioned with antilymphocyte serum, 100 cGy
      total body irradiation and cyclophosphamide were given islet cells of BALB/c(H
      2(b)), but group 3 were simultaneously given 30 x 10(6) BALB/c(H-2(b)) mice BMCs
      and islet cells similar to group 2. RESULTS: We obtained 5% to 6% allogeneic
      donor chimerism and 60% graft survival at 80 days after islet transplantation in
      group 3. We observed lymphocyte infiltration around the islet without destruction
      of endocrine cells and the presence of strong insulin/glucagon-stained cells in
      group 3. CONCLUSION: This minimal nonmyeloablative conditioning therapy induced
      donor chimerism and immune tolerance between MHC- and minor-disparate (BALB/c-
      >C57BL/6) mice and long-term islet graft survival was obtained through
      cotransplantation of bone marrow cells.

PMID- 15964394
TI  - The effect of pancreatic islet transplantation on progression of diabetic
      retinopathy and neuropathy.
AB  - INTRODUCTION: Pancreatic islet transplantation (PIT) has only become an effective
      treatment for type 1 diabetes mellitus within the past 4 years. As a result, the
      long-term effects of PIT on progression of diabetic neuropathy and retinopathy
      are unknown. The benefit of halting or improving diabetic neuropathy and
      retinopathy is of particular interest since most PIT recipients have not
      developed the advanced complications of diabetes. Herein, we describe the
      improvement and stabilization of diabetic neuropathy and retinopathy in 12 PIT
      recipients. PATIENTS AND METHODS: Between January 1, 2002, and June 30, 2004,
      there have been 12 patients who have received PIT. Currently, there are eight
      patients who have sufficient follow-up to assess the progression of diabetic
      retinopathy and neuropathy. To assess for disease progression, patients were
      examined by a single ophthalmologist and single neurologist throughout the study
      period. Eye exams were performed using a slit-lamp exam while neurological status
      was assessed using electromyelograms and clinical exams. RESULTS: All PIT
      recipients had decreases in hemoglobin A(1)C and increases in serum C-peptide.
      All study patients had stabilization of their retinopathic disease. One patient
      demonstrated improvement of retinopathy at 1 year posttransplant. Fifty percent
      of patients demonstrated improvement or stabilization of their diabetic
      neuropathy. One patient had mild reinnervation of the fingers and wrist extensors
      by clinical exam 1 year posttransplant. Four patients exhibited an average
      decrease of 19% in sural nerve conduction velocities. CONCLUSION: Our series has
      demonstrated that all PIT recipients have had stabilization of their diabetic
      retinopathy and that 50% of patients exhibited stabilization or even improvement
      of their diabetic neuropathy.

PMID- 15964396
TI  - Long-term parenteral nutrition in pediatric autoimmune enteropathies.
AB  - Severe and protracted or persistent diarrhea (SPD) is the most severe form of
      diarrhea in infancy and has also been defined as intractable diarrhea when it
      leads to dependence on total parenteral nutrition (TPN). One of the rare causes
      of SPD is represented by autoimmune enteropathy that is characterized by life
      threatening diarrhea mainly occurring within the first years of life, persistent
      villous atrophy in consecutive biopsies, resistance to bowel rest, and evidence
      of antigut autoantibodies. We evaluated 10 patients (seven boys, mean age at
      diagnosis 18 months; range: 0 to 160 months) fulfilling criteria of autoimmune
      enteropathy to assess dependence on TPN. TPN was first required in all patients
      to avoid dehydration and electrolytic imbalance. All patients were dependent on
      immunosuppressive therapy (steroid, azothioprine, cyclosporine, tacrolimus).
      Three patients died of sepsis: two during TPN while in the hospital, and one at
      home after he was weaned off TPN. Five patients are weaned off TPN after a mean
      period of 18 months; they are actually on oral alimentation with a cow milk-free
      diet after a period of enteral nutrition with elemental formula. One underwent
      total colectomy and bone marrow transplantation and one developed an IPEX
      syndrome. One patient is still dependent on TPN for 24 months. She is on home
      parenteral nutrition. Patients with diagnosis of IPEX syndrome require parenteral
      support with three or four infusion per week. TPN represents a fixed step in the
      management of autoimmune enteropathy, but it may be considered as an interim
      treatment while waiting for intestinal adaptation, at least in some selectioned
      case of autoimmune enteropathy. Bone marrow transplantation should be considered
      and reserved for those patients with severe complications due to home parenteral
      nutrition, or in those that are really dependent on parenteral nutrition.

PMID- 15964397
TI  - Use of prosthetic mesh in difficult abdominal wall closure after small bowel
      transplantation in adults.
AB  - Abdominal wall closure after intestinal transplantation in adult patients can be
      a difficult procedure. The main possibility offered by international experience
      is the use of myocutaneous flaps and abdominal wall transplantation. We report
      our experience in intestinal/multivisceral transplantation, including four
      difficult cases among 27 adult transplant recipients. Three patients underwent
      prosthetic mesh alone and one, a myocutaneous flap for abdominal closure after
      primary mesh positioning. We selected a mesh with a structure that allowed us to
      close the abdomen without creating adhesions and, at the same time, stimulating
      tissue repair. Two patients experienced local mesh infection, which has been kept
      under clinical control by antibiotics and daily medications till neoabdominal
      wall formation. The mesh was then removed. Another patient underwent mesh
      substitution for a suspicious fever. The last patient had mesh as a bridge for a
      subsequent myocutaneous flap from the thigh. All patients are in good health with
      well-functioning grafts and no need for parenteral nutrition. No enterocutaneous
      fistulae were detected.

PMID- 15964398
TI  - Embolization of a ruptured pseudoaneurysm with massive hemorrhage following
      pancreas transplantation: a case report.
AB  - Pseudoaneurysm associated with an arterioenteric fistula is rare, but its
      clinical manifestations may represent a dramatic event that involves diagnostic
      and therapeutic problems. We report a case of an arterioduodenal fistula related
      to a ruptured pseudoaneurysm after simultaneous pancreas-kidney transplantation
      (SPK) with massive gastrointestinal hemorrhage treated by embolization of the Y
      graft. A 51-year-old man with type I diabetes and end-stage renal disease
      underwent SPK. No rejection episodes were documented; the patient was discharged
      with normal pancreatic and renal function. Two months later the patient was
      readmitted for an episode of massive lower digestive bleeding and hypotension.
      The Y-graft was embolized in order to obtain a prompt arrest of the bleeding. The
      procedure was successful and the patient progressively recovered. Once the
      hypovolemia was completely corrected, the graft was removed. An arterioenteric
      fistula between donor mesenteric artery and duodenum was confirmed. Few reports
      exist in the literature regarding the development of a pseudoaneurysm after
      pancreas transplantation. To our best knowledge only one case of pseudoaneurysm
      rupture into donor duodenum has been recently published. In our case angiography
      recognized the site of the pseudoaneurysm and its rupture into donor duodenum.
      Embolization of the Y-graft appeared the most rapid, simple, and safe approach to
      obtain the prompt arrest of the massive bleeding. Embolization of the Y-graft may
      represent a valid option in the presence of life-threatening hemorrhage.

PMID- 15964399
TI  - The evaluation of apoptosis and reactive oxygen species in hematopoietic cells
      derived from heparinized cadaveric organ donors stored short-term at 4 degrees C.
AB  - Heparinized cadaveric organ donors are an important source of human organs and
      potentially of hematopoietic cells for transplantation purposes. The aim of this
      study was to evaluate the kinetics of programmed cell death in the hematopoietic
      cells harvested from these individuals and stored short-term at 4 degrees C. We
      also attempted to assess hematopoietic cell oxidation by measuring reactive
      oxygen species (ROS) generated by the mitochondria of stored cells. We found that
      these bone marrow cells harvested and stored at 4 degrees C for 7 days did not
      display a significant increase in programmed cell death. However, prolonged
      storage resulted in lower ROS production, indirectly giving evidence of
      activation of intracellular signaling proteins.

PMID- 15964400
TI  - Time-related changes in the incidence, severity, and clinical outcome of hepatic
      veno-occlusive disease in hematopoietic stem cell transplantation patients during
      the past 10 years.
AB  - Veno-occlusive disease (VOD) of the liver occurs in 10% to 50% of patients after
      hematopoietic stem cell transplantation (HSCT), ranging from a mild reversible
      disease to a fulminant course with a mortality rate close to 100%. We
      retrospectively evaluated the clinical signs, diagnosis, prognosis, therapy, and
      outcome of 13 hepatic VOD cases which developed after HSCT. A total of 193
      consecutive patients (age: 15-62 years; median 33 years) with various hematologic
      diseases underwent 197 HSCT (allogeneic HSCT, n = 128; autologous HSCT, n = 69).
      In general, the conditioning regimen consisted of cyclophosphamide combined
      either with total body irradiation or busulfan. Since 2000, to reduce hepatic
      complications, all patients received ursodexycolic acid and discontinuation of
      norethisterone which inhibits ovulation. VOD diagnosed clinically was mainly
      managed in supportive fashion. Five patients received thrombolytic therapy (t
      plasminogen activator [t-PA], n = 3; defibrotide [DF], n = 2). VOD developed in
      13 of 197 cases (6.6%). All except one were in the allogeneic group who had
      received a busulfan-containing conditioning regimen; Ten (77%) were severe.
      Thirty-three of 197 (17%) cases died before day 100 with VOD as the cause in
      eight (24%). All of the t-PA administered patients died with significant
      hemorrhagic complications. DF patients improved completely, even after renal and
      respiratory failure, despite high total bilirubin levels. Only one patient who
      received DF became a long-term survivor; the other died with sepsis during the
      following days. The dramatic improvement with regard to VOD during DF therapy was
      encouraging.

PMID- 15964401
TI  - Highly efficient transfection of human marrow stromal cells by nucleofection.
AB  - Human marrow stromal cells (hMSCs) are an attractive source for autologous cell
      and gene therapies. In this study, we developed a highly efficient transfection
      method for hMSCs. Although they tend to show efficient gene delivery, nonviral
      vectors offer several advantages over viral vectors for gene therapies. They are
      inexpensive to produce and suitable to adopt particularly with respect to little
      or no specific immune responses; they are simple to use; they entail easier large
      scale production; and they have a high degree quality control. hMSCs and rat
      marrow stromal cells were transfected with the plasmid pEGFP-N1 that encoded a
      green fluorescent protein component by using two nonviral methods: nucleofection
      and electroporation. Nucleofection provided a much better rate of transfer than
      electroporation particularly in hMSCs.

PMID- 15964402
TI  - Human leukocyte antigen allelic groups and haplotypes in a brazilian sample of
      volunteer donors for bone marrow transplant in Curitiba, Parana, Brazil.
AB  - Bone Marrow Transplant (BMT) is a lifesaving procedure for several diseases.
      Histocompatibility between host and donor is crucial for the success of this
      therapy. Since human leukocyte antigen (HLA) genes are the most polymorphic in
      humans, a foreknowledge of their frequencies and a vast register of volunteer
      donors are important for patients who need an unrelated donor. This research
      evaluated data from 3500 HLA-typed donors using PCR-SSP (One Lambda ABDRX kits,
      low/medium resolution). The allele and haplotype frequencies were calculated from
      the donor HLA typings. Among the total sample we observed that the allelic groups
      HLA-A*02, -B*35, and -DRB1*11 had frequencies of 0.228, 0.112, and 0.125,
      respectively. The haplotype HLA-A*01-B*08-DRB1*03 was the most frequent (0.024).
      We also compared our results with another study conducted in a Northeastern
      Brazilian population. The identification of the most common allelic groups and
      haplotypes is of great interest, not only to know the HLA composition of the
      population but also to search for the best HLA match for a transplant. However,
      the search for the perfect match depends on the eventual registration of every
      specific donor in the national registers for bone marrow donation.

PMID- 15964403
TI  - Antileukemic effect of interleukin-7-transduced bone marrow stromal cells in mice
      following allogeneic T-cell-depleted bone marrow transplantation.
AB  - Impaired immune reconstitution following allogeneic bone marrow transplantation
      (BMT) remains a major obstacle to its clinical application. In this study,
      interleukin (IL)-7-transduced bone marrow stromal cells (MSC-IL7, 1 x
      10(6)/mouse) were transfused into lethally irradiated C57BL/6 recipient mice. By
      day 40 after transplantation, the recipient mice were challenged with the
      lymphoma cell line EL4. MSC-IL7 co-transplantation protected recipient mice from
      leukemic mortality (MST >120 days after BMT vs mean survival time (MST) 70 days
      in the PBS group) It enhance the PFC count and DTH responses of recipients after
      transplantation. In conclusion, MSC mediated IL-7 gene therapy and may be a more
      feasible strategy to restore immune function following allo-TCD-BMT.

PMID- 15964404
TI  - Prolonged skin allograft survival in Scid mice reconstituted with isogeneic bone
      marrow stem cell antigen-1-positive cells and thymus tissue.
AB  - INTRODUCTION: Many studies indicate that tolerance induction is much more
      dependent on the maturation status of lymphocytes than the age of the animal. We
      hypothesized that direct persistent contact of bone marrow stem cells with graft
      alloantigen will result in tolerance to that antigen in the adult animal.
      MATERIAL AND METHODS: Severe combined immunodeficient mice (CB-17-Scid, H-2b)
      were reconstituted with isogeneic bone marrow stem cell antigen-1 (Sca-1)
      positive cells and grafted with fetal thymus (BMSC-T), followed by transplant of
      allogeneic skin grafts from C57BL/6 (H-2d) mice. The control group include CB-17
      non-Scid mice, CB-17-Scid mice, and CB-17 Scid mice pretransplanted with
      nonmodified isogeneic bone marrow cells and fetal thymus (BMC-T). RESULTS AND
      DISCUSSION: Skin allograft survival was significantly prolonged in the group
      pretransplanted with isogeneic BMSC-T compared the group of non-Scid mice and the
      group of Scid mice pretransplanted with BMC-T (59.6 days vs 7.1 days vs 11.7
      days). In 2 of 10 mice pretransplanted with BMSC-T, the skin allografts
      transplanted immediately after BMSC-T survived for more than 100 days, but the
      third-party skin allografts transplanted at 100 days after BMSC-T transplant were
      rejected. The results suggest direct persistent contact of bone marrow Sca-1
      positive cells with graft alloantigen may be a feasible approach to prolong
      allograft survival and induce tolerance in a small fraction of adult animals.

PMID- 15964405
TI  - Intraosseus transplantation of donor-derived hematopoietic stem and progenitor
      cells induces donor-specific chimerism and extends composite tissue allograft
      survival.
AB  - We investigated the effect of the intraosseous allotransplantation of the donor
      derived hematopoietic stem cells (HSC) CD90+ on chimerism induction and survival
      of rat hind limb transplants. Eighteen rat hind limb transplantations were
      performed between Lewis-Brown-Norway and Lewis rats in three groups. Isograft and
      allograft rejection controls received no treatment. In the experimental group,
      0.8 to 1.2 x 10(6) of separated and purified CD90+ HSC cells were transplanted
      intramedullary into the bone marrow cavity of the recipient's tibia during
      opposite hind limb transplantation, without immunosuppressive therapy.
      Transplants from isograft group survived indefinitely. Allograft controls
      rejected transplants on day 7 posttransplant. The injection of separated and
      purified CD90+ cells of the donor origin extended survival of the transplanted
      limbs up to 15 days in group III. We introduced a novel method of transplantation
      of the CD90+ cells of the donor origin into the recipient's bone marrow cavity.
      This technique resulted in extended allograft survival, without immunosuppressive
      therapy.

PMID- 15964406
TI  - A new method of bone marrow transplantation leads to extension of skin allograft
      survival.
AB  - Tolerance induction through allogeneic bone marrow transplantation is an
      alternative method to chronic immunosuppression in maintaining long-term
      allograft survival. In this article, we introduce a new method of bone marrow
      allotransplantation, which preserves its natural microenvironment and does not
      require marrow processing or recipient conditioning. A total of 43 skin graft
      transplantations were performed in nine experimental groups between isogeneic
      [Lewis to Lewis (LEW, RT1(1))] and allogeneic [Lewis x Brown Norway (LBN --> F1,
      RT1(1+n)) to Lewis] rats under 35-day protocol of alphabeta T-cell receptor (TCR)
      monoclonal antibody (mAb) and cyclosporine (CsA) protocol. Monotherapies combined
      with "crude" bone marrow transplantation resulted in extended survival up to 21
      days under CsA and up to 10 days under alphabeta-TCR mAb protocol. The use of
      combined protocol of alphabeta-TCRmAb/CsA with crude bone marrow transplantation
      resulted in the extension of skin allograft survival up to 65 days (P < .05).
      This new simple method of "crude" bone marrow allotransplantation without
      recipient conditioning is a promising, minimally invasive technique with a
      potential for direct clinical application.

PMID- 15964407
TI  - Cyclosporine and sirolimus interaction in a kidney transplant patient.
AB  - Cyclosporin A and sirolimus are becoming commonly used in immunosuppressive
      treatment in organ transplant patients. The drugs are both metabolized by
      cytochrome P450 3A4 and are substrates of P-glycoprotein. Thus, interaction
      between these drugs is possible. The case reported here illustrated that
      clinicians should be aware of this important drug-drug interaction.

PMID- 15964408
TI  - Impact of mycophenolate mofetil loading on drug exposure in the early
      posttransplant period.
AB  - Achieving adequate therapeutic levels of immunosuppressive medications is
      important in rejection prevention. This study examined exposure to mycophenolic
      acid (MPA) in kidney transplant patients within the first 5 days
      posttransplantation. METHODS: This single-center, nonrandomized study of first
      solitary kidney allograft recipients receiving cyclosporine (n = 116) or
      tacrolimus (n = 50) included patients who received either 1 g or 1.5 g of
      mycophenolate mofetil twice daily starting postoperatively. Exposure to MPA was
      measured at days 3 and 5 posttransplant using published limited sampling time
      equations. RESULTS: There were no significant differences in exposure in the
      cyclosporine-treated patients receiving 3-g (n = 22) compared to 2-g (n = 94)
      daily doses (AUC([0-12]) 33.8 +/- 10.0 mg*h/L versus 30.1 +/- 9.7 mg*h/L, P =
      .20, respectively). About half the patients in both groups had AUC([0-12]) <30
      mg*h/L on days 3 and 5 posttransplant. On the other hand, there was significantly
      greater exposure on day 3 in the tacrolimus-treated patients receiving 3 g (n =
      21) compared to 2 g (n = 29) daily (AUC([0-12]) 43.1 +/- 9.0 mg*h/L versus 36.8
      +/- 11.1 mg*h/L, P = .016, respectively). On day 3 one (4.8%) patient receiving 3
      g had an AUC([0-12]) of <30 mg*h/L; whereas, eight (27.5%) receiving 2 g were
      below this level (P = .068). The AUC([0-12]) levels were not different on day 5.
      CONCLUSIONS: Loading with higher doses of mycophenolate mofetil results in
      greater exposure and a trend toward more patients in the therapeutic window
      within the first week for tacrolimus- but not for cyclosporine-treated patients.

PMID- 15964409
TI  - A rat model of chronic allograft liver rejection.
AB  - INTRODUCTION: The aim of this study was to develop a rat model of chronic
      irreversible rejection, which is a major causes of late graft loss and
      retransplantation after orthotopic liver allotransplantation. METHODS: Allogeneic
      liver transplantation was performed in a rat combination of Dark Agouti (DA) to
      Brown Norway (BN). Group A was left without treatment, group B received
      cyclosporine' (CsA; 1 mg/kg/d) and group C, CsA (4 mg/kg/d). Animals were
      followed for 6 months. Liver tissue was harvested to construct a time course of
      histological changes after liver transplantation using histopathological and
      morphometric techniques. We compared the total histological score of rejection
      activity index and survival rates. RESULTS: In untreated animals, irreversible
      acute rejection developed, all animals died within 15 days. In the low-dose CsA
      group, all animals that survived more than 30 days developed moderate to severe
      manifestations of chronic liver rejection, with graft infiltration, ductular
      damage or proliferation, obliterative arteriopathy, and liver fibrosis. No
      apparent histological alterations were observed in group C. Survival analysis
      showed significant differences between the three groups. CONCLUSIONS: In the rat
      strain combination of DA --> BN with low-dose immunosuppression, early mild
      inflammation was followed by the development of chronic rejection.

PMID- 15964410
TI  - Guidelines for prevention and management of complications following kidney
      transplantation in rats.
AB  - Kidney transplantation in rats is a useful model for microsurgery,
      transplantation, and immunology studies. Our aim was to analyze various
      techniques of kidney transplantation in rats with emphasis on guidelines for the
      prevention and management of complications. Complications were categorized into
      general, vascular, and urological types and respectively attributed to long
      transplantation time, core body temperature drop, nonreplaced intraoperative
      blood loss, anastomosis failure, and ureteral anastomoses with stents or
      cannulas, which increase the risk of calculus formation. In conclusion, to
      decrease the complication rates the animal should be placed on a heating pad. For
      hemodynamic stability NaCl should be administered subcutaneously. To reduce the
      risk of thrombosis, ice-cold saline containing heparin should be administered.
      Vascular complications, which mainly depend on the microsurgeon's expertise, can
      be prevented by meticulous surgical technique (preferably an end-in-end
      anastomosis). The main urinary complications can be minimized by avoiding stents
      and cannulas and focusing on using techniques like the bladder-patch technique.

PMID- 15964411
TI  - Microsurgical techniques in rat heterotopic small bowel transplantation: analysis
      of 450 cases.
AB  - BACKGROUND: We sought to review 450 rat small bowel transplantation (SBT)
      operations having a modified microsurgical technique to discuss the key steps for
      a successful operation. METHODS: Four hundred fifty rat heterotopic small bowel
      transplantations were performed in 3 stages: the first 80 cases were a training
      stage, the following 330 cases were for formal experiments, and, in the last
      stage, 40 cases were to analyze the relationship between the duration of cold
      preservation and recipient mortality. For all cases, revascularization of the
      graft was accomplished by an end-to-side anastomosis between the donor superior
      mesenteric artery or aorta and the recipient infra-renal aorta, and cuffed end-to
      end anastomosis between the donor portal vein and the left renal vein of the
      recipient. The duration of each operation, graft warm ischemia time, and
      recipient survival rate were compared. RESULTS: In the first stage, the graft
      warm ischemia time was about 90 minutes where as it was only 35 minutes in the
      second stage. The longterm survival rates (>5 days) of recipients were 8.8% and
      97.3%, respectively. In the 3rd stage, long cold preservation period
      significantly increased recipient mortality. CONCLUSIONS: Graft warm ischemia
      time was a key issue associated with recipient mortality; a well-trained,
      simplified microsurgical anastomosis between graft superior mesenteric artery and
      recipient aorta accomplished in a shorter time rendered intravenous transfusion
      not essential for the recipient.

PMID- 15964412
TI  - Evaluation of intraoperative infusion solution using a complete anhepatic model
      in baby pigs.
AB  - Compared to cadaveric liver transplantation, living-related liver transplantation
      (LRLT) has the physiological advantage of avoiding hemodynamic changes due to the
      nonsystemic clamping of the inferior vena cava (IVC). However, metabolic changes
      in the level of blood glucose and lactate usually occur during the anhepatic
      phase in LRLT. For pediatric patients, intraoperative infusions have the
      potential to maintain immature homeostasis during LRLT. In the present study, a
      complete anhepatic model of baby pigs with nonsystemic clamping of IVC, which
      mimics the procedure of pediatric LRLT, was established using a heparin-coated
      tube as an internal shunt lactate Ringer solution (LR, Lactec), acetate Ringer
      solution (AR, VeenF), and a solution comprising acetate Ringer with 1% glucose
      (AR-G, Phisio140) were tested using piglets. Hemodynamic and metabolic (blood gas
      analysis, electrolytes, blood lactate, and glucose) changes were observed during
      the anhepatic phase. Although no major difference was observed in hemodynamic
      parameters, arterial blood gas data, or concentration of electrolytes among the
      three solution groups, significant progressive hyperlactatemia was observed in
      the LR group. Also, though severe hypoglycemia was found in the LR and AR groups,
      the AR-G group maintained blood glucose levels throughout the anhepatic phase. To
      conclude, using the simplified pig anhepatic model, we evaluated various
      solutions for pediatric LRLT.

PMID- 15964413
TI  - Active spleno-femoral shunt avoids splanchnic congestion during portal triad
      occlusion: an experimental study.
AB  - Portal triad occlusion (PTO) is often performed during hepatic resections for
      trauma or malignancies to minimize intraoperative blood loss. The pringle
      maneuver is also regularly required during liver transplantation. This maneuver
      leads to temporary hepatic ischemia and may be associated with splanchnic blood
      flow congestion, promoting undesirable hemodynamic disturbances in some patients.
      Veno-venous bypass is a useful, easily performed technique that may avoid those
      deleterious hemodynamic effects of PTO. We tested the hypothesis that an active
      spleno-femoral shunt maintains hemodynamic stability and promotes complete
      decompression of the mesenteric bed, avoiding intestinal mucosal blood
      congestion, during PTO. METHODS: Seven dogs (17.2 +/- 0.9 kg) were subjected to
      45 minutes of hepatic ischemia during which there was an active spleno-femoral
      shunt. Systemic hemodynamics were evaluated through Swan-Ganz and arterial
      catheters. Splanchnic perfusion was assessed by portal vein blood flow and
      hepatic artery blood flow (PVBF and HABF, ultrasonic flowprobe), intestinal
      mucosal-arterial pCO(2) gradient (D(t-a)pCO(2), tonometry), and regional O(2)
      derived variables. RESULTS: No significant changes in systemic and regional
      parameters were observed during the ischemia period. During reperfusion, a
      significant decrease in mean arterial pressure, PVBF, and arterial pH was
      observed. A significant increase in ALT and D(t-a)pCO(2) (4.8 +/- 2.5 to 18.9 +/-
      3 mm Hg) was also observed following hepatic blood flow restoration. CONCLUSION:
      Spleno-femoral shunt maintains systemic hemodynamic stability, with an effective
      decompression of the splanchnic bed during portal triad occlusion. The
      deleterious hemodynamic and metabolic effects observed during reperfusion period,
      such as transitory hypotension, high D(t-a)pCO(2), and acidemia, were associated
      with an isolated hepatic ischemia-reperfusion injury, not with the blood
      congestion in the splanchnic bed.

PMID- 15964414
TI  - Trophic effect of enteral rehabilitative therapy in rat small bowel
      transplantation.
AB  - INTRODUCTION: We aimed to observe the trophic effects on graft structure and
      recipient metabolism of enteral rehabilitative therapy in rat small bowel
      transplantation (SBT). METHODS: Forty-eight recipients of rat allogeneic
      heterotopic SBT (Sprague-Dawley to Wistar rat) were divided into four groups
      randomly according to the presence of glutamine or growth hormone in the
      nutritional support regimen. We compared the histologic indices of graft mucosa
      and metabolic variables, including changes in body weight, nitrogen balance,
      urinary 3-methyl histidine excretion, and plasma albumin levels during 14 days
      after transplantation. RESULTS: Glutamine and growth hormone promoted recovery of
      graft structure and improved recipient protein metabolism, as evidenced by
      indices of the enteral rehabilitative therapy. CONCLUSIONS: Glutamine and growth
      hormone potentiated their effects in enteral rehabilitative therapy, which
      produced potent trophic effects on graft structure and recipient metabolism in
      rat SBT.

PMID- 15964415
TI  - Immunosuppression by combined use of cyclosporine and resveratrol in a rat liver
      transplantation model.
AB  - INTRODUCTION: Despite continued progress in the development of immunosuppressive
      agents, allograft rejection remains an important cause of morbidity and mortality
      after liver transplantation. We examined the effect of intraperitoneal injection
      of cyclosporine (CsA) and resveratrol (Res) on allograft rejection after liver
      transplantation in rats. METHODS: Male Sprague-Dawley rats were selected as
      donors and male Wistar rats as recipients for a rejection model. The recipients
      were divided into three groups after orthotopic liver transplantation (OLTx): in
      the combination group both Res (100 mg/kg) and CsA (20 mg/kg) were given by
      intraperitoneal route once a day, whereas in the CsA group or control group CsA
      (20 mg/kg) or vehicle buffer was given. The survival period, serum chemistry,
      production of some cytokines, activation of transcription factor NF- kappaB, and
      histopathological findings were then compared among them. RESULTS: The mean
      survival period after OLTx in the combination group was significantly longer than
      that in the CsA group or control group (P < .05 and P < .01). On posttransplant
      day 7, the serum albumin level significantly improved, the serum total bile acid
      and alanine aminotransferase levels were significantly lower, the serum
      interleukin-2 and interferon-gamma levels were significantly lower, and the
      activation of transcription factor NF-kappaB in peripheral blood T lymphocytes
      was significantly suppressed in the combination group in comparison with those in
      the CsA group (all P < .05) or control group (all P < .01), and a histological
      examination revealed apparent difference in the severity of rejection between the
      combination group and CsA group (P < .05) or control group (P < .01). CONCLUSION:
      The combined use of CsA and Res has a stronger immunosuppressive effect on
      hepatocytes under allograft rejection in comparison with the sole use of CsA. Res
      might serve as a novel supplementary immunosuppressive agent for reducing the
      severity of hepatic allograft rejection in rats.

PMID- 15964416
TI  - Transforming growth factor beta1-modified donor cell transfusion induced allo
      heart tolerance.
AB  - The therapeutic value of the transforming growth factor beta 1 (TGF-beta1) in
      transplantation has been reported; however, cell-mediated gene therapy using TGF
      beta1 is not a widespread application in organ transplantation. This study was
      performed to evaluate whether TGF-beta1-modified donor spleen cell-specific
      transfusion could induce tolerogenicity and prolong allograft survival in rat
      heterotopic heart transplantation. Stable TGF-beta1-transduced spleen cells were
      established. Wistar rat splenic T-cell responses to donor spleen cells that
      received TGF-beta1-transduced were severely impaired. Survival of Sprague-Dawley
      cardiac allografts in Wistar rats given TGF-beta1-modified donor spleen cells (5
      x 10(6), 7 days before transplantation), was extended modestly but significantly.
      Liposome transduction of donor spleen cells to overexpress TGF-beta1 is
      associated with marked impairment of their T-cell allostimulatory activity but
      only modest prolongation of allo-heart survival.

PMID- 15964417
TI  - Cyclosporine-induced coronary endothelial dysfunction: is tetrahydrobiopterin the
      solution?
AB  - BACKGROUND: Coronary endothelial dysfunction after heart transplantation is
      predictive of cardiac allograft vasculopathy. Immunosuppressive drugs,
      particularly cyclosporine may contribute to this dysfunction by a direct effect.
      Tetrahydrobiopterin (BH(4)) is a potent antioxidant and an essential cofactor of
      nitric oxide biosynthesis. The purpose of this study was to investigate whether
      BH(4) could reverse the endothelial dysfunction induced by cyclosporine. METHODS:
      A previously described in vitro model of drug incubation in Krebs-bicarbonate
      solution (4 degrees C, 48 hours) of porcine epicardial coronary arteries was
      used. Coronary endothelial function studies were performed in organ chamber
      experiments after incubation with cyclosporine (10(-4) mol/L) in the presence or
      absence of 6-methyltetrahydropterin (MH(4) [0.1 mol/L], a BH(4) analog) to assess
      its effect on the cyclosporine-induced endothelial dysfunction. RESULTS: The
      average doses of PGF2(alpha) required to attain 50% of the maximal contraction to
      KCl was significantly lower (P < .001) in the cyclosporine group (8.6 +/- 1.94 x
      10(-6) mol/L) compared to the control group (24.8 +/- 5.2 x 10(-6) mol/L).
      Exposure to cyclosporine induced a significant decrease in endothelium-dependent
      relaxations to serotonin (5HT) (% E(max) [5HT]: 77% +/- 4%; P < .05). Addition of
      MH(4) significantly reversed this impaired response (% E(max) [5HT]: 62% +/- 4%;
      P < .05). No alterations of relaxation were observed with bradykinin in both
      groups. Endothelium-independent relaxations to sodium nitroprussiate were fully
      preserved. CONCLUSIONS: These results suggest a significant protective role of
      BH(4) on coronary endothelial function following exposure to cyclosporine, which
      could reduce the incidence of endothelial dysfunction and cardiac allograft
      vasculopathy following cardiac transplantation.

PMID- 15964418
TI  - Effect of cyclosporine A on total homocysteine level in a rabbit model.
AB  - BACKGROUND: Moderate hyperhomocysteinemia is an independent risk factor for
      cardiovascular disease. Cyclosporine (CsA) has been suggested to interfere with
      folate-assisted remethylation of homocysteine, thus causing hyperhomocysteinemia.
      But, this issue is controversial. In this experimental study, we attempted to
      determine the association between CsA administration and total homocysteine
      levels. Working with rabbits that have normal creatinine levels, we obviated the
      misleading effects of renal functional variations, which are the most important
      confounding factors affecting total homocysteine level. METHODS: Male New Zealand
      rabbits fed a standard quantity of diet received 10 days of subcutaneous
      injections of 10 mg/kg per day CsA. After these loading doses, CsA (20 mg/kg) was
      administered subcutaneously three times a week for 20 days. After first 30 days,
      the rabbits were followed for another 30 days without CsA therapy. Plasma
      creatinine, BUN, and total homocysteine levels were measured on days 0, 10, 30,
      and 60. RESULTS: There were no significant changes in BUN results on days 0, 10,
      30, and 60 (P > .05). There was a slight, but significant, increase in mean
      creatinine levels during CsA administration (P < .01). However, the mean
      creatinine levels remained in the normal ranges during the 60 days of study. No
      significant changes were observed in total homocysteine levels (P > .05) compared
      to baseline, 10-, 30-, and 60-day values. CONCLUSION: Our experimental research
      minimized confounding factors. It showed that CsA does not increase total
      homocysteine levels, confirming clinical studies that reported no association
      between CsA and total homocysteine.

PMID- 15964419
TI  - Peritransplant and long-term secretion of interleukin-1beta in cyclosporine
      treated syngeneic rats allografted with islets of langerhans.
AB  - Interleukin-1beta (IL-1beta) is one of the proinflammatory cytokines that may
      mediate primary nonfunction of islets of Langerhans, limiting the success of
      allogeneic transplantation. The aim of this study was to assess differences
      between the secretion of IL-1beta as well as glycemia in peri- and long-term
      periods of intraportal islet allo-transplantation with or without cyclosporine
      (CyA) immunosuppression. Inbred Wistar albino rats were transplanted
      intraportally with rat islets isolated by collagenase digestion. The two
      recipient groups (6 rats/group) were: group 1, control, islet transplantation
      (ITX) without any treatment and group 2, CyA-treated via the femoral muscle on
      days -1, 0, +1, and +2. Serum IL-1beta (pg/mL) levels were measured by ELISA on
      days 0 (pre-ITX), +1, +2, and +195. Tail vein blood was used to evaluate glycemia
      (mg/dL). No major differences were observed in IL-1beta secretion on days 0, +1,
      or +195 between the groups. Immunosuppressive treatment produced significantly
      lower secretion in group 2 (P < .002) on day +2. Significantly greater secretions
      were detected at days +195, +1, and +195 compared to days 0, +2, and +2,
      respectively (P < .002; P < .008; P < .002). Positive correlations were observed
      between IL-1beta levels on days +1 and +2 (r = 0.845, P < .034). The mean values
      in groups 1 and 2 on days 0, +1, and +2 were 140.6 +/- 4.62 vs 119.1 +/- 12.12,
      73.1 +/- 19.59 vs 88.3 +/- 14.08, 106.5 +/- 13.79 vs 92.5 +/- 15.8, respectively.
      No animal in group 1 displayed glycemia while three group 2 animals did at day
      +195. However, a negative correlation was found between IL-1beta on day 0 and
      glycemia on day +195 (r = -0.999, P < .026). Our results suggest that IL-1beta
      secretion, which is detrimental for islet engraftment, decreases at
      peritransplant day +2, but is upregulated during long-term graft survival both in
      controls and in CyA-treated recipients.

PMID- 15964420
TI  - CTLA4-Fas ligand gene transfer mediated by adenovirus induce long-time survival
      of murine cardiac allografts.
AB  - BACKGROUND: Fas ligand gene transfer to induce peripheral allograft tolerance in
      animal models has shown controversial results. The immunosuppression effects
      mediated by engineered FasL depend on whether alloreactive T cells are
      selectively deleted. In the present study, we tested the feasibility of a
      strategy to induce long-time survival by fusing CTLA4-FasL gene transfer in vivo.
      METHODS: Cardiac allografts from DA(RT-1(a)) rats were transplanted
      heterotopically into the abdomens of LEW(RT-1(1)) rats. Plaque units (5x10(9)) of
      either AdCTLA4-FasL, AdCTLA4Ig, or AdEGFP were administered via the portal vein
      immediately after cardiac transplantation. The frequencies of helper T lymphocyte
      precursors (HTLp) and cytotoxic T lymphocyte precursors (CTLp) were determined by
      a combined single limiting dilution assay on days 5 and 20 after transplantation.
      RESULTS: Cardiac allograft survival was significantly prolonged by either AdCTLA4
      FasL or AdCTLA4Ig treatment(mean survival times [MST] of 71.0 +/- 3.7 and 45.7 +/
      2.4, respectively, n = 6) compared with untreated hosts or animals treated with
      AdEGFP(MST of 5.7 +/- 0.5 and 5.2 +/- 0.4, respectively, n = 6). In addition,
      treatment with AdCTLA4-FasL led to significantly prolonged allograft survival
      compared with AdCTLA4Ig treatment. Furthermore, the frequencies of HTLp and CTLp
      on day 20 among rats treated with AdCTLA4-FasL was lower than those on day 5,
      whereas frequencies of HTLp and CTLp on day 20 were similar with those on day 5
      in the other groups. CONCLUSION: These results suggest that administration of an
      adenovirus encoding fusion CTLA4-FasL gene to rat recipients effectively
      decreased the size of alloreactive T cells and induced long-term survival of
      cardiac allografts.

PMID- 15964421
TI  - Donor leukocytes combine with immunosuppressive drug therapy to prolong limb
      allograft survival.
AB  - Donor leukocytes administered at the time of transplantation may prolong organ
      allograft survival. This study examined the effectiveness of donor leukocyte
      injection combined with immunosuppression for limb transplantation across the
      strong histocompatibility barrier of a Brown Norway donor to a Lewis recipient.
      Eight animals received 6 x 10(7) donor leukocytes injected on the day of
      transplantation. From day 1, FK506 (2 mg/kg/d), mycophenolate mofetil (MMF) (15
      mg/kg/d), and prednisone (0.5 mg/kg/d) were administered for 2 weeks. After week
      2, prednisone and MMF were both tapered by 20% of the initial dosage per week.
      After week 7, the animals received only FK506 (2 mg/kg/d). From week 8, FK506 was
      tapered to the maintenance dose of 0.8 mg/kg/d at week 10 and was stopped on week
      24. A control group of 8 animals underwent identical treatment except that the
      leukocyte injection was omitted. Rejection was observed in both groups during
      FK506 monotherapy; however, the onset of early rejection episodes was
      significantly later, the period for reversal of the first rejection was
      significantly shorter, and the dosage of FK506 at the time of rejection was
      significantly lower among leukocyte-treated recipients. After completion of
      immunosuppression, survival was modestly prolonged in the leukocyte-treated
      group. One animal is surviving without immunosuppression on day 234. This trial
      of donor leukocyte injection combined with immunosuppression in limb
      transplantation showed a modest, but significant, improvement in outcome.

PMID- 15964422
TI  - Effects of epigallocatechin gallate on the hemolysis induced by cyclosporine.
AB  - INTRODUCTION: Hemolysis is one of the side effects of cyclosporine (CsA) therapy,
      in part due to, increased production of free radical species by CsA.
      Epigallocatechin gallate (EGCG), which acts as a highly efficient free radical
      scavenger, may have a protective effect on CsA-induced hemolysis. In this study,
      we measured the degree of hemolysis of as well as the amounts of hydrogen
      peroxide level and malondialdehyde produced by normal human erythrocytes (RBCs)
      incubated with CsA and with EGCG. METHODS: Human RBCs were incubated as follows.
      In group 1, 4.2 x 10(6)/mL RBCs were incubated with Cremophore EL. In group 2,
      the RBCs were incubated with only 167 microg/mL EGCG. In group 3, the RBCs were
      incubated with 1.67 mg/mL CsA. In group 4, the RBCs were incubated with CsA plus
      EGCG. RESULTS: The degree of hemolysis in group 2 (53.8 +/- 3.8) was
      significantly higher than that in group 1 (7.0 +/- 1.0). The degree of hemolysis
      in group 3 (86.2 +/- 2.2) was significantly higher than that in group 1 and group
      2. The degree of hemolysis in group 4 (74.9 +/- 2.9) was significantly higher
      than in group 1 and in group 2, but lower than that in group 3. The hydrogen
      peroxide and malondialdehyde levels paralleled the degree of hemolysis.
      CONCLUSIONS: These results suggest that CsA can induce free radical-mediated
      hemolysis, which can be partially prevented with EGCG.

PMID- 15964423
TI  - Circulating endothelial cells in renal transplant recipients.
AB  - Circulating endothelial cells (CECs) are a marker of endothelial injury and
      endothelial dysfunction. We measured CECs in 95 patients with functioning renal
      transplants at risk of premature cardiovascular (CV) disease and in normal
      control subjects. We were unable to demonstrate consistent relationships between
      CEC levels and conventional CV risk factors in transplant recipients. However,
      CEC levels were increased in patients with a history of rejection. We conclude
      that CECs are of little use as a marker of CV risk in this population but may be
      a useful marker to monitor allograft rejection.

PMID- 15964424
TI  - Effects of serum from patients with acute liver failure due to paracetamol
      overdose on human hepatocytes in vitro.
AB  - OBJECTIVE: Our goal was to investigate the effects of serum from patients with
      acute liver failure due to paracetamol (acetaminophen) overdose on the function
      of human hepatocytes in vitro. METHODS: Freshly isolated human hepatocytes plated
      on collagen-coated culture plates were, incubated (24 hours 37 degrees C) in
      medium containing pooled human sera (0%-80%) obtained from normal individuals or
      from patients with acute liver failure due to paracetamol overdose. The effects
      of the sera on cell function were assessed using MTT, [14C]-leucine
      incorporation, and cytochrome P450 (CYP1A1/2) activity assays. RESULTS: The
      overall cellular metabolic activity was significantly greater at all
      concentrations after exposure to acute liver failure serum compared to normal
      serum. There were no significant differences in the decreases produced by pooled
      acute liver failure and normal sera at concentrations up to 80% on the [14C]
      leucine incorporation or CYP1A1/2 activity. CONCLUSION: The overall cell
      function/activity of human hepatocytes was not impaired in vitro on exposure to
      serum from patients with acute liver failure due to paracetamol overdose.

PMID- 15964425
TI  - Interleukin-2alpha receptor in membrane lipid rafts.
AB  - Acute allograft rejection is driven by production of cytokines such as
      interleukin(IL)-2 that activate and expand alloreactive T cells by ligating high
      affinity IL-2alpha receptors. Lipid rafts on the membranes of T cells may be the
      functional microdomains for IL-2alpha receptor. Flow cytometric analysis was
      performed for expression of CD25 (IL-2alpha receptor) on the surface of T cells.
      Lipid rafts were isolated by discontinuous sucrose density gradient
      ultracentrifugation. The localization of IL-2Ralpha in fractions isolated from
      sucrose density gradients was determined by immunoblotting and detected by
      chemiluminescence. Cells were stimulated with IL-2 and expression of CD25 (IL
      2alpha receptor) on the surface of T cells was 37.08%. Immunoblot analysis of
      fractions from sucrose gradients revealed that a large proportion of IL-2Ralpha
      was localized in lipid rafts. Lipid rafts are the functional microdomains for IL
      2alpha receptors.

PMID- 15964426
TI  - Effect of mechanical stress imposition on co-culture of hepatic parenchymal and
      nonparenchymal cells: possibility of stimulating production of regenerating
      factor.
AB  - The effect of mechanical stress generated within a three-dimensional bioreactor
      on the co-culture of hepatic parenchymal cells (PC) and hepatic nonparenchymal
      cells (NPC) was assessed to develop a bioartificial liver that can produce
      factors accelerating liver regeneration. A rotating radial flow bioreactor was
      used to provide mechanical stress to a co-culture of PC and NPC that were
      isolated from rats. They were co-cultured in the reactor under static or dynamic
      conditions. Albumin, interleukin-6 (IL-6), hepatocyte growth factor (HGF), and
      lactate dehydrogenase (LDH) were measured at intervals. Electron microscopy was
      also performed. LDH was not significantly different between the static and
      mechanical stress-loaded cultures, while albumin and interleukin-6 levels were
      higher in the latter at all sampling times. Only the co-cultures loaded with
      mechanical stress produced HGF in the early stage of culture (hours 3 and 6).
      Histologically, the cells retained their structure when cultured under dynamic
      conditions. These results suggested that an appropriate level of mechanical
      stress enabled co-cultures of PC and NPC to produce IL-6, HGF, and other factors
      that accelerate liver regeneration.

PMID- 15964427
TI  - Redefining risks after TIA and minor ischaemic stroke.

PMID- 15964428
TI  - Anti-Wolbachia treatment for lymphatic filariasis.

PMID- 15964429
TI  - Telomerase expression in somatic cells.

PMID- 15964430
TI  - Collaboration in cardiovascular stem-cell research.

PMID- 15964431
TI  - Semantics and ethics of human embryonic stem-cell research.

PMID- 15964432
TI  - Stem-cell therapy: hope and hype.

PMID- 15964433
TI  - AIDS in Uganda: the human-rights dimension.

PMID- 15964434
TI  - Carol Jacobs: new chair of Global Fund Board wants to engage private sector.

PMID- 15964435
TI  - Fiscal space: response from World Bank and IMF.

PMID- 15964436
TI  - Sensorineural hearing loss in children.

PMID- 15964437
TI  - Influenza vaccines in healthy children.

PMID- 15964438
TI  - Influenza vaccines in healthy children.

PMID- 15964440
TI  - Malaria: yet another war for Afghanistan.

PMID- 15964441
TI  - Trends in childhood cancer incidence in Europe, 1970-99.

PMID- 15964443
TI  - Manuscript decision? Please pick a number.

PMID- 15964442
TI  - Eliminating neglected diseases in Africa.

PMID- 15964444
TI  - Guidelines for sterilisation in India.

PMID- 15964445
TI  - Introduction of the medical emergency team (MET) system: a cluster-randomised
      controlled trial.
AB  - BACKGROUND: Patients with cardiac arrests or who die in general wards have often
      received delayed or inadequate care. We investigated whether the medical
      emergency team (MET) system could reduce the incidence of cardiac arrests,
      unplanned admissions to intensive care units (ICU), and deaths. METHODS: We
      randomised 23 hospitals in Australia to continue functioning as usual (n=11) or
      to introduce a MET system (n=12). The primary outcome was the composite of
      cardiac arrest, unexpected death, or unplanned ICU admission during the 6-month
      study period after MET activation. Analysis was by intention to treat. FINDINGS:
      Introduction of the MET increased the overall calling incidence for an emergency
      team (3.1 vs 8.7 per 1000 admissions, p=0.0001). The MET was called to 30% of
      patients who fulfilled the calling criteria and who were subsequently admitted to
      the ICU. During the study, we recorded similar incidence of the composite primary
      outcome in the control and MET hospitals (5.86 vs 5.31 per 1000 admissions,
      p=0.640), as well as of the individual secondary outcomes (cardiac arrests, 1.64
      vs 1.31, p=0.736; unplanned ICU admissions, 4.68 vs 4.19, p=0.599; and unexpected
      deaths, 1.18 vs 1.06, p=0.752). A reduction in the rate of cardiac arrests
      (p=0.003) and unexpected deaths (p=0.01) was seen from baseline to the study
      period for both groups combined. INTERPRETATION: The MET system greatly increases
      emergency team calling, but does not substantially affect the incidence of
      cardiac arrest, unplanned ICU admissions, or unexpected death.

PMID- 15964446
TI  - Long-term survival and vascular event risk after transient ischaemic attack or
      minor ischaemic stroke: a cohort study.
AB  - BACKGROUND: Determinants of survival and of risk of vascular events after
      transient ischaemic attack (TIA) or minor ischaemic stroke are not well defined
      in the long term. We aimed to restudy these risks in a prospective cohort of
      patients after TIA or minor ischaemic stroke (Rankin grade< or =3), after 10
      years or more. METHODS: We assessed the survival status and occurrence of
      vascular events in 2473 participants of the Dutch TIA Trial (recruitment in 1986
      89; arterial cause of cerebral ischaemia). We included 24 hospitals in the
      Netherlands that recruited at least 50 patients. Primary outcomes were all-cause
      mortality and the composite event of death from all vascular causes, non-fatal
      stroke, and non-fatal myocardial infarction. We assessed cumulative risks by
      Kaplan-Meier analysis and prognostic factors with Cox univariate and multivariate
      analysis. FINDINGS: Follow-up was complete in 2447 (99%) patients. After a mean
      follow-up of 10.1 years, 1489 (60%) patients had died and 1336 (54%) had had at
      least one vascular event. 10-year risk of death was 42.7% (95% CI 40.8-44.7). Age
      and sex-adjusted hazard ratios were 3.33 (2.97-3.73) for age over 65 years, 2.10
      (1.79-2.48) for diabetes, 1.77 (1.45-2.15) for claudication, 1.94 (1.42-2.65) for
      previous peripheral vascular surgery, and 1.50 (1.31-1.71) for pathological Q
      waves on baseline electrocardiogram. 10-year risk of a vascular event was 44.1%
      (42.0-46.1). After falling in the first 3 years, yearly risk of a vascular event
      increased over time. Predictive factors for risk of vascular events were similar
      to those for risk of death. INTERPRETATION: Long-term secondary prevention in
      patients with cerebral ischaemia still has room for further improvement.

PMID- 15964447
TI  - Antiviral medications to prevent cytomegalovirus disease and early death in
      recipients of solid-organ transplants: a systematic review of randomised
      controlled trials.
AB  - BACKGROUND: Antiviral prophylaxis is commonly used in recipients of solid-organ
      transplants with the aim of preventing the clinical syndrome associated with
      cytomegalovirus infection. We undertook a systematic review to investigate
      whether this approach affects risks of cytomegalovirus disease and death.
      METHODS: Randomised controlled trials of prophylaxis with antiviral medications
      for cytomegalovirus disease in solid-organ-transplant recipients were identified.
      Data were combined in meta-analyses by a random-effects model. FINDINGS: Compared
      with placebo or no treatment, prophylaxis with aciclovir, ganciclovir, or
      valaciclovir significantly reduced the risks of cytomegalovirus disease (19
      trials, 1981 patients; relative risk 0.42 [95% CI 0.34-0.52]), cytomegalovirus
      infection (17 trials, 1786 patients; 0.61 [0.48-0.77]), and all-cause mortality
      (17 trials, 1838 patients; 0.63 [0.43-0.92]), mainly owing to lower mortality
      from cytomegalovirus disease (seven trials, 1300 patients; 0.26 [0.08-0.78]).
      Prophylaxis also lowered the risks of disease caused by herpes simplex or zoster
      virus, bacterial infections, and protozoal infections, but not fungal infection,
      acute rejection, or graft loss. Meta-regression showed no significant difference
      in the risk of cytomegalovirus disease or all-cause mortality by organ
      transplanted or cytomegalovirus serostatus; no conclusions were possible for
      cytomegalovirus-negative recipients of negative organs. In trials of direct
      comparisons, ganciclovir was more effective than aciclovir in preventing
      cytomegalovirus disease. Valganciclovir and intravenous ganciclovir were as
      effective as oral ganciclovir. INTERPRETATION: Prophylaxis with antiviral
      medications reduces the risk of cytomegalovirus disease and associated mortality
      in recipients of solid-organ transplants. This approach should be used routinely
      in cytomegalovirus-positive recipients and in cytomegalovirus-negative recipients
      of organs positive for the virus.

PMID- 15964448
TI  - Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a
      double-blind, randomised placebo-controlled trial.
AB  - BACKGROUND: Wolbachia endosymbionts of filarial nematodes are vital for larval
      development and adult-worm fertility and viability. This essential dependency on
      the bacterium for survival of the parasites has provided a new approach to treat
      filariasis with antibiotics. We used this strategy to investigate the effects of
      doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria
      bancrofti. METHODS: We undertook a double-blind, randomised, placebo-controlled
      field trial of doxycycline (200 mg per day) for 8 weeks in 72 individuals
      infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants
      were randomly assigned by block randomisation to receive capsules of doxycycline
      (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring
      microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Follow-up
      assessments were done at 5, 8, 11, and 14 months after the start of treatment.
      Analysis was per protocol. FINDINGS: One person from the doxycycline group died
      from HIV infection. Five (doxycycline) and 11 (placebo) individuals were absent
      at the time of ultrasound analysis. Doxycycline treatment almost completely
      eliminated microfilaraemia at 8-14 months' follow-up (for all timepoints
      p<0.001). Ultrasonography detected adult worms in only six (22%) of 27
      individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at
      14 months after the start of treatment (p<0.0001). At the same timepoint,
      filarial antigenaemia in the doxycycline group fell to about half of that before
      treatment (p=0.015). Adverse events were few and mild. INTERPRETATION: An 8-week
      course of doxycycline is a safe and well-tolerated treatment for lymphatic
      filariasis with significant activity against adult worms and microfilaraemia.

PMID- 15964449
TI  - Blood vessels engineered from human cells.
AB  - Tissue engineering has made considerable progress in the past decade, but
      advances have stopped short of clinical application for most tissues. We
      postulated that an obstacle in engineering human tissues is the limited
      replicative capacity of adult somatic cells. To test this hypothesis, the
      effectiveness of telomerase expression to extend cellular lifespan was assessed
      in a model of human vascular tissue engineering. Telomerase expression in
      vascular cells isolated from elderly patients enabled the successful culture of
      engineered autologous blood vessels. Engineered vessels may one day provide a
      source of bypass conduit for patients with atherosclerotic disease.

PMID- 15964450
TI  - Congenital adrenal hyperplasia.
AB  - Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a
      disorder of the adrenal cortex characterised by cortisol deficiency, with or
      without aldosterone deficiency, and androgen excess. Patients with the most
      severe form also have abnormalities of the adrenal medulla and epinephrine
      deficiency. The severe classic form occurs in one in 15,000 births worldwide, and
      the mild non-classic form is a common cause of hyperandrogenism. Neonatal
      screening for CAH and gene-specific prenatal diagnosis are now possible. Standard
      hormone replacement fails to achieve normal growth and development for many
      children with CAH, and adults can experience iatrogenic Cushing's syndrome,
      hyperandrogenism, infertility, or the development of the metabolic syndrome. This
      Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and
      management of CAH, and provides an overview of clinical challenges and future
      therapies.

PMID- 15964451
TI  - Recognition and management of complications of new recreational drug use.
AB  - Use of illicit drugs in clubs and large dance parties (so-called raves) is a
      burgeoning cultural trend. Such recreational drug use is associated with several
      medical complications, both acute and longlasting. Although few, if any, of the
      drugs currently used in recreational venues are truly new, their patterns and
      context of use have changed (a great deal in some instances). For some of these
      substances, this cultural repackaging of the drug experience has resulted in
      various medical disorders that have previously gone undocumented. This review
      aims to help treating physicians recognise and manage complications associated
      with the use of new drugs in clubs, including methylenedioxymethamfetamine,
      ephedrine, gamma-hydroxybutyrate; gamma-butyrolactone, 1,4-butanediol,
      flunitrazepam, ketamine, and nitrites. We also alert researchers to specific
      toxic effects of club-drugs on which more basic information is needed.

PMID- 15964452
TI  - GHB-sense and sociability.

PMID- 15964453
TI  - Apollo at the front.

PMID- 15964454
TI  - When the patient comes back.

PMID- 15964455
TI  - I am a better doctor now.

PMID- 15964456
TI  - A pregnant woman with headaches, seizures, and hypertension.

PMID- 15964457
TI  - Tort reform is only a stopgap measure.

PMID- 15964458
TI  - Hepatic surgery: current techniques and outcomes.

PMID- 15964459
TI  - Endoluminal therapy for GERD: the beginning, but will it be a reality?

PMID- 15964460
TI  - What's the flap over pilonidal disease?

PMID- 15964461
TI  - Living on the edge: current concepts in the management of congenital
      diaphragmatic hernia.

PMID- 15964463
TI  - Inhaled nitric oxide.

PMID- 15964464
TI  - Fibrin sealants: valuable asset or just an additional expense.

PMID- 15964465
TI  - An update on the surgical management of rectal cancer.

PMID- 15964466
TI  - Abdominal pain and vomiting in a middle-aged woman.

PMID- 15964467
TI  - George Washington Crile, MD.

PMID- 15964468
TI  - Chronic perforation of the sigmoid colon by foreign body.
AB  - Colorectal foreign bodies (FBs) may be ingested or introduced transanally and
      then migrate proximally. Without a reliable history, it may be impossible to
      determine which way a certain colorectal FB gained access. We present a case of a
      nonverbal mentally retarded boy with a flat piece of plastic impacted in the
      sigmoid colon, the colonoscopic extraction of which failed. He underwent
      laparotomy more than a year later to remove the FB, where chronic perforation of
      the sigmoid colon was discovered. The perforation was sealed with extensive
      adhesions to the pelvic wall, and histologically, the colon showed a chronic
      granulomatous reaction. We discuss the types, presentations, and diagnosis of
      intestinal perforation with FBs. Chronic perforation may present with radiologic
      and pathologic features that suggest inflammatory bowel disease.

PMID- 15964469
TI  - Diversity in general surgery: a period of progress.
AB  - OBJECTIVE: Although 1996 to 2002 was a period of declining interest in general
      surgery (GS) among U.S. medical students (USS), most categorical general surgery
      (C-GS) training positions offered in the National Residency Matching Program
      (NRMP) continued to fill. We measured the impact of the decreasing U.S. student
      applicant volume on C-GS match outcomes and GS resident workforce composition
      over this time period. DESIGN: Match outcomes were analyzed for 7 applicant
      categories. Subsequent GS resident workforce compositions were analyzed for
      proportions of U.S. allopathic medical school graduates (USG), osteopathic
      medical graduates (OMG), Canadian MG (CMG), foreign MG (FMG), female physicians,
      and African-American physicians. Mantel-Haenzel chi-square tests measured trends
      in match percentages, C-GS positions filled, and GS workforce composition. All p
      values are 2-sided. RESULTS: Increasing match percentages for USS applicants (p <
      0.0001) and USG (p = 0.001), with a decreasing percentage of C-GS positions
      filled by these applicants (p < 0.0001), were from declining applicant volumes.
      Increasing match percentage for non-U.S. allopathic medical applicants reflected
      increases in both applicant volumes and matched applicants, with an increasing
      percentage of C-GS positions filled by these applicants (p < 0.0001). The
      subsequent resident workforce included increasing proportions of FMGs and OMGs
      (each p < 0.001); proportions of USG MDs and CMGs decreased (p < 0.0001 and p <
      0.02, respectively). Concurrently, there were increasing numbers and proportions
      of female physicians (p < 0.0001) and African-American physicians (p < 0.0001) in
      the general surgery resident workforce. CONCLUSIONS: Declining interest among
      U.S. students in GS has resulted in a workforce comprised of residents from a
      broad range of educational backgrounds, but also it has provided an opportunity
      for progress toward achievement of a GS resident physician workforce more
      equitably representative of the racial and gender composition of our society at
      large.

PMID- 15964470
TI  - Factors influencing surgical career decisions.
AB  - OBJECTIVE: The purpose of this project is to evaluate factors that residents
      consider when choosing a career in surgery or a surgical subspecialty. Once these
      factors are identified, surgical residency programs may use the information in
      their recruiting efforts to attract the most qualified applicants for
      postgraduate surgical training. DESIGN: A descriptive survey consisting of 20
      questions was conducted. Surgical residents were surveyed about student loan
      debt, career decisions and influencing factors, and demographic data. SETTING: A
      2-page, Institutional Review Board-approved, survey was mailed to program
      directors of 40 general surgery residency programs. Included in the packet were
      copies of the survey, a letter to the program director, and a self-addressed
      prestamped envelope for return of the completed survey. The program directors
      were asked to have their residents complete the survey during a normally
      scheduled meeting and to collect and return the surveys. PARTICIPANTS: General
      surgery residents in residency programs randomly chosen throughout the country
      were surveyed. These residents included all postgraduate levels of training.
      RESULTS: Among 6 choices for entering a surgical residency, a strong desire to
      become a surgeon was the response chosen most often by residents. Over 50% of
      those surveyed indicated that they planned to pursue subspecialty training.
      Family ties was the most quoted influencing factor for choosing a geographical
      location for practice. Amount of student loan debt correlated with the perception
      of medical school being a financially wise decision, yet had little influence on
      the decision to subspecialize. CONCLUSIONS: A strong desire and passion for
      surgery was the predominant reason for choosing a career in surgery in this
      survey. Only 15% of general surgery residents surveyed intend to join the
      workforce as general surgeons. With the rising average age of the general
      population, this implies a significant shortage of general surgeons in the near
      future.

PMID- 15964471
TI  - Glomus tumor of the gastric antrum: case report.

PMID- 15964472
TI  - Surgical experience in children with biliary atresia treated with
      portoenterostomy.
AB  - OBJECTIVE: Biliary atresia is the result of a fibrosing destructive inflammatory
      process affecting intrahepatic and extrahepatic bile ducts, which lead to
      cirrhosis and portal hypertension. Without surgical intervention, mortality
      reaches 100%. The 5-year survival rate after portoenterostomy ranges from 13% to
      60%, with approximately 60% of patients requiring liver transplantation at a
      later stage because of insufficient bile flow. METHODS: This retrospective
      analysis includes 30 consecutive patients undergoing portoenterostomy for biliary
      atresia at our hospital. RESULTS: The 5-year actuarial survival of the 30
      patients was 68%. Thirteen patients (43.3%) died 3 days to 7 years after
      portoenterostomy. Four patients (13.3%) underwent liver transplantation 3 to 24
      months after the Kasai procedure with a 100% survival. In 65% of patients without
      presence of cirrhosis, the portoenterostomy was successful, compared with 35% of
      cases with liver cirrhosis (p = 0.0148). Liver cirrhosis with extrahepatic
      biliary atresia alone was present in 5 of 17 patients (29%) as compared with 8 of
      12 patients (66%) with intrahepatic biliary hypoplasia in addition to
      extrahepatic biliary atresia and cirrhosis. CONCLUSIONS: Portoenterostomy remains
      the treatment of choice for patients with extrahepatic biliary atresia. However,
      the presence of cirrhosis portends a poorer prognosis and may be an indication
      for early transplantation. Cirrhosis is more commonly present in the setting of
      intrahepatic biliary hypoplasia and may account for the lower success rates of
      portoenterostomy in this group of patients. Five-year survival of the female
      patients was 88% as compared with 55% of the male patients.

PMID- 15964473
TI  - The changing surgical residency.

PMID- 15964474
TI  - Reclaiming the lost art of listening.

PMID- 15964475
TI  - Healing our health care system: a plan to provide service and quality care.

PMID- 15964476
TI  - Hippocrates versus hypocrisy: defending medicine from defensive medicine.

PMID- 15964477
TI  - Health care in the United States: "If I was Czar".

PMID- 15964478
TI  - Rabies human diploid cell vaccine elicits cross-neutralising and cross-protecting
      immune responses against European and Australian bat lyssaviruses.
AB  - The ability of antibodies elicited against the rabies human diploid cell vaccine
      (HDCV) to neutralise European bat Lyssaviruses (EBLV types-1 and -2), Australian
      bat Lyssavirus and classical rabies virus (RABV) has been evaluated using
      modified fluorescent antibody virus neutralisation (mFAVN) assays. Ninety-six
      percent (48 of 50) of the human post-vaccinated sera tested cross-neutralised
      these viruses (>or=0.5 IU/ml). Cross-protection experiments using inbred mice
      (RIII, k/k haplotype) were also assessed. Mice were given HDCV (twice by the
      intra-peritoneal route) and challenged (intra-cranially or peripherally) with a
      lethal dose (25 MLD(50)) of the individual viruses. The vaccine conferred
      statistically significant protection in 80--100% of animals challenged via the
      peripheral route. Levels of protection were lower following intra-cranial (i.c.)
      challenge. Our data provides strong evidence for broad spectrum cross
      neutralisation and cross-protection of phylogroup I lyssaviruses using rabies
      HDCV.

PMID- 15964479
TI  - Cost-effectiveness of universal childhood hepatitis A vaccination in Chile.
AB  - Hepatitis A is an important public health problem in Chile. Childhood vaccination
      has reduced hepatitis A rates in several countries, prompting this evaluation of
      its cost-effectiveness in Chile. Using a Markov model, we project mass
      vaccination would reduce hepatitis A cases among birth cohort members and their
      personal contacts >80%. Vaccination costs of US dollars 5.3-6.4 million would be
      offset by US dollars 9.2-9.4 million reductions in disease costs. Further,
      approximately 70 fatal infections would be averted and >4600 quality-adjusted
      life years would be saved. This analysis supports the cost-effectiveness of
      universal childhood hepatitis A vaccination in Chile.

PMID- 15964480
TI  - Influence of glycosylphosphatidylinositol anchorage on the efficacy of DNA
      vaccines encoding Plasmodium yoelii merozoite surface protein 4/5.
AB  - Immune responses induced to DNA vaccination vary considerably and depend on a
      variety of factors, including the physical form in which the antigen is expressed
      by target cells and presented to the immune system. Data on the effect of these
      factors will aid improved design of DNA vaccines and facilitate their further
      development. We examined the effect of different forms of surface anchoring on
      the immunogenicity of a DNA vaccine. A number of constructs were generated
      encoding Plasmodium yoelii merozoite surface protein 4/5 (PyMSP4/5) with or
      without its C-terminal glycosylphosphatidylinositol (GPI) attachment signal,
      replacing the endogenous GPI signal of PyMSP4/5 with that of mouse decay
      accelerating factor (DAF), a well-established model for GPI-anchoring in
      mammalian cells, or the transmembrane anchor and cytoplasmic tail of mouse tissue
      factor (TF). All constructs were demonstrated to express the full-length PyMSP4/5
      in transfected COS cells and induce PyMSP4/5-specific antibodies in mice. The GPI
      attachment signal of PyMSP4/5 was found to function poorly in mammalian cells and
      result in a much lower level of PyMSP4/5 expression in vitro than its mammalian
      counterpart. The DNA vaccine containing the mammalian GPI attachment signal
      induced the highest levels of antibodies and impacted Ig isotype distribution,
      consistent with the presence of a CD1-restricted pathway of Ig formation to GPI
      anchored membrane proteins. Despite the induction of specific antibodies, none of
      these DNA vaccines induced sufficient levels of antibodies to protect mice
      against a lethal challenge with P. yoelii.

PMID- 15964482
TI  - Identification of novel antigens that protect against systemic meningococcal
      infection.
AB  - Systemic infection with Neisseria meningitidis leads to a devastating,
      septicaemic illness with a high mortality, particularly in children. Currently,
      there are no vaccines to prevent disease caused by strains of N. meningitidis
      serogroup B, the commonest isolate in developed countries. Here, we describe the
      identification of vaccine candidates that protect mice against lethal challenge
      with this bacterium. A total 11 meningococcal proteins that are necessary for
      establishing systemic infection were expressed as recombinant antigens and
      assessed for their ability to protect animals against live bacterial challenge;
      the lactate permease (LctP) and ExbB, which is required for iron acquisition,
      elicited protective immunity. Both LctP and ExbB are expressed by a wide range of
      pathogenic isolates of N. meningitidis. Targeting bacterial factors required for
      pathogenesis may lead to new vaccines to protect individuals from this important
      human pathogen.

PMID- 15964481
TI  - Modified anthrax fusion proteins deliver HIV antigens through MHC Class I and II
      pathways.
AB  - T cell-based HIV vaccine candidates have focused on eliciting both CD4- and CD8
      mediated responses. One challenge in vaccine development is the successful
      introduction and presentation of exogenous antigen to elicit an immune response.
      Modified bacterial toxins have been studied extensively as intracellular delivery
      agents because of their unique capability to translocate antigen across the cell
      membrane without affecting cell viability. Modified anthrax toxin lethal factor
      (LFn) fusion protein is able to effectively induce anti-HIV cytotoxic T
      lymphocytes in the absence of protective antigen (PA) and is being evaluated as a
      vaccine candidate. Here we describe, for the first time, the processing and
      presentation of LFn fusion proteins by the MHC Class II pathway. The ability of
      LFn--HIV to induce both CD8- and CD4-mediated responses may have relevance in
      current approaches to vaccine design. Furthermore, the translocation and
      presentation of antigens occurs in the absence of PA, which proposes a modified
      molecular mechanism of antigen presentation by the anthrax toxin model.
      Additionally, we found that LFn--HIV is specific and sensitive in detecting HIV
      specific CD4(+) and CD8(+) T cell responses in T cell assays, further broadening
      the value of this antigen delivery system as a useful immunologic tool.

PMID- 15964483
TI  - Safety and immunogenicty of RTS,S/AS02A candidate malaria vaccine in Gambian
      children.
AB  - RTS,S/AS02A is a pre-erythrocytic malaria vaccine candidate in which a portion of
      the circumsporozoite surface protein (CSP) of Plasmodium falciparum is
      genetically linked to hepatitis B surface antigen (HBsAg) coexpressed in yeast
      with unfused HBsAg. The resulting particulate antigen is formulated with the
      adjuvant system AS02A. We have initiated the paediatric clinical development of
      this vaccine by conducting two sequential Phase I studies in children: a study in
      older children (6--11 years), followed by a second study in younger children (1-
      5 years). In each study, a double-blind, randomised controlled, staggered, dose
      escalation design was used to evaluate 10 microg RTS,S dose (10 microg RTS,S in
      0.1mL AS02A), 25 microg dose (25 microg RTS,S in 0.25mL AS02A) and finally a 50
      microg dose (50 microg RTS,S in 0.5mL AS02A) of the RTS,S/AS02A candidate malaria
      vaccine administered according to a 0-, 1- and 3-month vaccination schedule.
      Safety and reactogenicity were evaluated before moving to a higher dose level.
      The RTS,S/AS02A vaccine was safe at all dose levels, in both age groups. No
      serious adverse events related to vaccination were reported. The frequency of
      local Grade 3 symptoms was low but tended to increase with increasing dose level.
      Grade 3 general adverse events in the RTS,S/AS02A groups were infrequent and of
      short duration. The majority of local and general Grade 3 symptoms resolved or
      decreased in intensity within 48h. The pattern and intensity of reactogenicity
      seen in these studies are similar to those of previous studies with RTS,S/AS02A.
      All doses were highly immunogenic for anti-CSP and anti-HBsAg antibodies. The
      pooled anti-CSP antibody data from the two studies showed that the 25 microg dose
      and 50 microg dose anti-CSP antibody response were similar at both dose levels.
      However, the immunogenicity of the 10 microg dose anti-CSP response was
      significantly lower than that of either the 50 microg or 25 microg dose. The 25
      microg dose was selected for future studies of RTS,S/AS02A in paediatric
      populations.

PMID- 15964484
TI  - Long-term efficacy of hepatitis B vaccine, booster policy, and impact of
      hepatitis B virus mutants.
AB  - The long-term efficacy of hepatitis B vaccine, long-term effectiveness of
      hepatitis B immunisation programmes, immune memory induced by hepatitis B
      vaccine, current booster policies, and impact of hepatitis B virus mutants on
      immunisation programmes were reviewed at the Viral Hepatitis Prevention Board
      (VHPB) meeting in Sevilla, Spain, March 2004. The main focus was on universal
      vaccination programmes with data being presented from Italy, Saudi Arabia,
      Singapore, Spain, Taiwan, Thailand, The Gambia, and USA (Alaska).

PMID- 15964485
TI  - Sleep-dependent motor memory plasticity in the human brain.
AB  - Growing evidence indicates a role for sleep in off-line memory processing,
      specifically in post-training consolidation. In humans, sleep has been shown to
      trigger overnight learning on a motor-sequence memory task, while equivalent
      waking periods produce no such improvement. But while the behavioral
      characteristics of sleep-dependent motor learning become increasingly well
      characterized, the underlying neural basis remains unknown. Here we present
      functional magnetic resonance imaging data demonstrating a change in the
      representation of a motor memory after a night of sleep. Subjects trained on a
      motor-skill memory and 12 hours later, after either sleep or wake, were retested
      during functional magnetic resonance imaging. Following sleep relative to wake,
      regions of increased activation were expressed in the right primary motor cortex,
      medial prefrontal lobe, hippocampus and left cerebellum; changes that can support
      faster motor output and more precise mapping of key-press movements. In contrast,
      signal decreases were identified in parietal cortices, the left insular cortex,
      temporal pole and fronto-polar region, reflecting a reduced need for conscious
      spatial monitoring and a decreased emotional task burden. This evidence of an
      overnight, systems-level change in the representation of a motor memory holds
      important implications for acquiring real-life skills and in clinical
      rehabilitation following brain trauma, such as stroke.

PMID- 15964486
TI  - Expression of P2X purinoceptors during rat brain development and their inhibitory
      role on motor axon outgrowth in neural tube explant cultures.
AB  - Extracellular ATP is well known as a neurotransmitter and neuromodulator in the
      CNS of adults. However, little is known about the involvement of ATP during the
      development of mammalian brain. In the present study, we have examined the
      expression pattern of P2X receptor subtype mRNA and protein during perinatal rat
      brain development (from embryonic day (E) 10 to postnatal day (P) 16 brain).
      While P2X3 receptors appeared early at E11, they declined in the stages that
      follow. P2X2 and P2X7 receptors were expressed from E14 onwards, while P2X4, P2X5
      and P2X6 receptors were expressed from P1 onwards. P2X1 receptor expression was
      not observed in any of the developmental ages examined. We investigated the
      effect of 100 microM ATP and alpha,beta-methylene ATP (alpha,beta-meATP;
      selective agonist for P2X1, P2X2/3 and P2X3 receptors) on motor axon outgrowth in
      collagen-embedded neural tube explant cultures. Both ATP- and alpha,beta-meATP
      treated neural tubes showed a significant reduction in neurite outgrowth compared
      with the control explants. This inhibitory effect could not be reproduced by
      uridine triphosphate. In conclusion, all P2X receptor subtypes, except for P2X1,
      were strongly represented in the developing rat brain. ATP was shown to inhibit
      motor axon outgrowth during early embryonic neurogenesis, most likely via the
      P2X3 receptor. It is speculated that P2X7 receptors may be involved in programmed
      cell death during embryogenesis and that P2X4, P2X(5) and P2X6 receptors might be
      involved in postnatal neurogenesis.

PMID- 15964487
TI  - Involvement of mitochondrial potential and calcium buffering capacity in
      minocycline cytoprotective actions.
AB  - Minocycline, a semisynthetic derivative of tetracycline, displays beneficial
      activity in neuroprotective in models including, Parkinson disease, spinal cord
      injury, amyotrophic lateral sclerosis, Huntington disease and stroke. The
      mechanisms by which minocycline inhibits apoptosis remain poorly understood. In
      the present report we have investigated the effects of minocycline on
      mitochondria, due to their crucial role in apoptotic pathways. In mitochondria
      isolated suspensions, minocycline failed to block superoxide-induced swelling but
      was effective in blocking mitochondrial swelling induced by calcium. This latter
      effect might be mediated through dissipation of mitochondrial transmembrane
      potential and blockade of mitochondrial calcium uptake. Consistently, minocycline
      fails to protect SH-SY5Y cell cultures against reactive oxygen species-mediated
      cell death, including malonate and 6-hydroxydopamine treatments, but it is
      effective against staurosporine-induced cytotoxicity. The effects of this
      antibiotic on mitochondrial respiratory chain complex were also analyzed.
      Minocycline did not modify complex IV activity, and only at the higher
      concentration tested (100 microM) inhibited complex II/III activity. Other
      members of the minocycline antibiotic family like tetracycline failed to induce
      these mitochondrial effects.

PMID- 15964488
TI  - Hippocampal neurokinin-1 receptor and brain-derived neurotrophic factor gene
      expression is decreased in rat models of pain and stress.
AB  - Acute or chronic stress can alter hippocampal structure, cause neuronal damage,
      and decrease hippocampal levels of the neurotrophin brain-derived neurotrophic
      factor (BDNF). The tachykinin substance P and its neurokinin-1 (NK-1) receptor
      may play a critical role in neuronal systems that process nociceptive stimuli;
      their importance in stress-activated systems has recently been demonstrated by
      the antidepressant-like actions of NK-1 receptor antagonists. However, the
      functional similarities between neurokinin receptors in the hippocampus and those
      in sensory systems are poorly understood, as is the significance of hippocampal
      NK-1 receptor in the context of chronic pain. Therefore, we investigated the
      effects of immobilization stress or inflammatory stimuli on NK-1 receptor and
      BDNF gene expression in the rat hippocampus. Rats received an acute or chronic
      immobilization stress, or an acute (formalin) or chronic (complete Freund's
      adjuvant) inflammatory stimulus to the right hind paw. Subsequently hippocampal
      volume and specific gravity were measured and NK-1 receptor and BDNF mRNA levels
      quantified using ribonuclease protection assays. Results showed that either
      stress or pain down-regulates expression of both NK-1 receptor and BDNF genes in
      the hippocampus. Hippocampal volume was increased by either pain or stress; this
      may be due to edema (decreased specific gravity). Thus, BDNF and NK-1 receptor
      gene plasticity may reflect sensory activation or responses to neuronal injury.
      These data may provide useful markers of hippocampal activation during chronic
      pain, and suggest similarities in the mechanisms underlying chronic pain and
      depression.

PMID- 15964489
TI  - Inhibition of the cloned delayed rectifier K+ channels, Kv1.5 and Kv3.1, by
      riluzole.
AB  - The action of riluzole, a neuroprotective drug, on cloned delayed rectifier K+
      channels (Kv1.5 and Kv3.1) was examined using the whole-cell patch-clamp
      technique. Riluzole reversibly inhibited Kv1.5 currents in a concentration
      dependent manner with an IC50 of 39.69+/-2.37 microM. G-protein inhibitors
      (pertussis toxin and GDPbetaS) did not prevent this inhibition of riluzole on
      Kv1.5. No voltage-dependent inhibition by riluzole was found over the voltage
      range in which channels are fully activated. Riluzole shifted the steady-state
      inactivation curves of Kv1.5 in a hyperpolarizing direction in a concentration
      dependent manner. It accelerated the deactivation kinetics of Kv1.5 in a
      concentration dependent-manner, but had no effect on the steady-state activation
      curve. Riluzole exhibited a use-independent inhibition of Kv1.5. The effects of
      riluzole on Kv3.1, the Shaw-type K+ channel were also examined. Riluzole caused a
      concentration-dependent inhibition of Kv3.1 currents with an IC50 of 120.98+/
      9.74 microM and also shifted the steady-state inactivation curve of Kv3.1 in the
      hyperpolarizing direction. Thus, riluzole inhibits both Kv1.5 and Kv3.1 currents
      in a concentration-dependent manner and interacts directly with Kv1.5 by
      preferentially binding to the inactivated and to the closed states of the
      channel.

PMID- 15964490
TI  - Ethanol versus lipopolysaccharide-induced hypothermia: involvement of urocortin.
AB  - The urocortin1 (Ucn1) neurons of the mid-brain-localized Edinger-Westphal nucleus
      (EW) are robustly responsive to ethanol (EtOH) administration, and send
      projections to the dorsal raphe nucleus (DRN), which contains corticotropin
      releasing factor type 2 receptors (CRF2) that are responsive to Ucn1. In
      addition, the DRN has been shown to be involved in regulation of body
      temperature, a function greatly affected by EtOH administration. The goal of the
      present study was to identify the role that the urocortinergic projections from
      the EW to the DRN have in mediating EtOH-induced and lipopolysaccharide (LPS)
      induced hypothermia. Male C57BL6/J mice were used. Groups of mice underwent
      cannulation of the DRN, and then received i.p. injections of EtOH (2g/kg) or LPS
      (600 microg/kg or 400 microg/kg), followed by intra-DRN injections of artificial
      cerebrospinal fluid (aCSF) or anti-sauvagine (aSVG) (55 pmol), a CRF2 antagonist.
      Separate groups of mice received single intra-DRN injections of Ucn1 (20 pmol),
      CRF (20 pmol) or aCSF. For all experiments, core temperatures were monitored
      rectally every 30 min for several hours post-injection. Both EtOH and LPS induced
      hypothermia, and aSVG significantly attenuated this effect after EtOH; however,
      there was no significant attenuation of hypothermia after either dose of LPS.
      Ucn1 injection also caused hypothermia, while CRF injection did not. These data
      demonstrate that EtOH-induced hypothermia, but not LPS-induced hypothermia, may
      involve Ucn1 from EW acting at CRF2 receptors in the DRN.

PMID- 15964491
TI  - The primate amygdala and reinforcement: a dissociation between rule-based and
      associatively-mediated memory revealed in neuronal activity.
AB  - To investigate the role of the primate amygdala in stimulus-reinforcement
      association learning, the activity of single amygdala neurons was recorded in
      macaques during two memory tasks. In a visual discrimination task, a population
      of neurons (17/659) was analyzed which responded differentially to a visual
      stimulus which always indicated that the primary reinforcer fruit juice could be
      obtain if the monkey licked, and a different visual stimulus that indicated that
      the primary reinforcer aversive saline would be obtained if the monkey licked.
      Most (16/17) of these neurons responded more to the reward-related than the
      aversive visual stimulus. In a recognition memory task, the majority (12/14
      analyzed) of these neurons responded equally well to the trial unique stimuli
      when they were shown as novel and the monkey had to not lick in order to avoid
      saline, and when they were shown a second time as familiar and the monkey used
      the rule that if he licked, fruit juice would be obtained. The responses of these
      amygdala neurons thus reflect the direct associations of stimuli with
      reinforcement, but do not reflect the reward value of the stimuli when this must
      be assessed based on a rule (in the recognition memory task, that a stimulus will
      be punished the first time it is shown, and rewarded the second). This finding
      also shows that these amygdala neurons respond to relatively novel stimuli in the
      same way as they do to stimuli that have become rewarding by stimulus
      reinforcement association learning. This provides a neural basis for relatively
      novel stimuli to be treated as rewarding, and approached.

PMID- 15964492
TI  - Hypoxia recruits a respiratory-related excitatory pathway to brainstem premotor
      cardiac vagal neurons in animals exposed to prenatal nicotine.
AB  - The most ubiquitous form of arrhythmia is respiratory sinus arrhythmia in which
      the heart beat slows during expiration and heart rate increases during
      inspiration. Whereas respiratory sinus arrhythmia benefits pulmonary gas exchange
      respiratory dysfunction presents a major challenge to the cardiorespiratory
      system. Hypoxia evokes a pronounced bradycardia mediated by increases in
      parasympathetic cardiac activity. It has been hypothesized that the fatal events
      in sudden infant death syndrome (SIDS) are exaggerated cardiorespiratory
      responses to hypoxia. This study tests whether premotor cardiac vagal neurons
      receive rhythmic respiratory-related excitatory synaptic inputs during normoxia
      and hypoxia, and if animals exposed to nicotine in the prenatal period have
      exaggerated responses to hypoxia. Premotor cardiac vagal neurons in the nucleus
      ambiguus were identified in rats by the presence of a fluorescent tracer in
      medullary slices that generate rhythmic inspiratory-related motor discharge.
      Respiratory activity was recorded from the hypoglossal nerve and excitatory
      synaptic events in cardiac vagal neurons were isolated using patch clamp
      techniques. Adult female rats were implanted with osmotic minipumps that
      delivered nicotine at a level approximately equivalent to those that occur in
      moderate to heavy smokers. During normal eupneic respiration, as well as during
      hypoxia, premotor cardiac vagal neurons from control animals did not receive any
      rhythmic respiratory-related excitatory inputs. However in animals exposed to
      nicotine throughout the prenatal period respiratory bursts during hypoxia
      dramatically increased the frequency of excitatory synaptic events in cardiac
      vagal neurons. In summary, in animals exposed to nicotine throughout the prenatal
      period, but not in unexposed animals, respiratory bursts that occur during
      hypoxia dramatically increase the frequency of excitatory synaptic events in
      cardiac vagal neurons. This study establishes a likely neurochemical mechanism
      for the heart rate responses to hypoxia and a link between prenatal nicotine
      exposure and exaggerated bradycardia responses during hypoxia that may contribute
      to sudden infant death syndrome.

PMID- 15964493
TI  - Risk factors for spontaneous rupture of liver abscess caused by Klebsiella
      pneumoniae.
AB  - To identify risk factors for spontaneous rupture of liver abscess (SRLA), a
      retrospective study on patients with liver abscess caused by Klebsiella
      pneumoniae was performed. Of the 140 enrolled patients with liver abscess caused
      by K. pneumoniae, 8 (5.7%) experienced SRLA. In comparison to those with
      nonruptured liver abscess (NRLA), patients with SRLA were found to have
      significantly higher proportions of diabetic mellitus (100% versus 62.1%, P =
      0.003), larger abscess size (mean of maximal diameter 7.8 versus 6.1 cm, P =
      0.043), gas formation in abscess (87.5% versus 23.5%, P < 0.001), and left
      hepatic lobe involvement (50.0% versus 16.5%, P = 0.018). K. pneumoniae serotypes
      K1 and K2 were the predominant microorganisms isolated in both patients with NRLA
      and SRLA. Pulsed-field gel electrophoresis-generated fingerprinting of K.
      pneumoniae isolates from patients with SRLA revealed that these pathogens were
      nongenetically related.

PMID- 15964494
TI  - Diarrheal illness among deployed U.S. military personnel during Operation Bright
      Star 2001--Egypt.
AB  - In the fall of 2001, approximately 15,000 U.S. military personnel participated in
      a military exercise in the northwestern Egyptian desert. To assess the prevalence
      and impact of diarrhea and enteropathogen distribution, we conducted a post
      deployment survey and a case series study. A departure convenience sampling (n =
      3725) was used in the post-deployment survey. Overall, 9.3% reported diarrhea,
      2.6% sought medical care, and 2.8% stopped or decreased their work for at least a
      day. Among those reporting diarrhea, 41.7% had symptoms for less than 2 days,
      43.5% had symptoms from 2-5 days, and 14.8% had symptoms for more than 5 days. In
      the case series study, pathogens were identified in 53.6% of the 129 cases
      enrolled. Pathogens identified included enterotoxigenic E. coli (n = 53),
      enteroaggregative E. coli (n = 13), Cryptosporidium (n = 9), Campylobacter jejuni
      (n = 7), noroviruses (n = 7), Shigella flexneri (n = 2), rotavirus (n = 2), and
      Entamoeba histolytica (n = 2). Among those seeking care for diarrhea, two thirds
      reported a decreased ability or inability to perform their jobs for at least one
      day, but overall, diarrhea was much less prevalent than in past surveys in this
      region, with minimal impact on the mission.

PMID- 15964495
TI  - Limited clinical utility of Clostridium difficile toxin testing in infants in a
      pediatric hospital.
AB  - Previous studies have shown high rates of asymptomatic carriage of toxin
      producing Clostridium difficile in infants. We performed a retrospective case
      control study comparing infants younger than 1 year old with diarrhea and C.
      difficile toxin (CDT) in the stool, to age-matched controls with diarrhea lacking
      CDT in the stool. We found no difference in clinical characteristics including
      fever, vomiting, or hematochezia. Treatment with metronidazole had no significant
      effect on the clinical outcome. Alternative etiologies for diarrhea (most
      commonly viral) were found in more than 50% of patients in both groups. We
      recommend that other causes of diarrhea be considered before C. difficile colitis
      in this age group.

PMID- 15964496
TI  - Reevaluation of the cefepime minimal inhibitory concentrations and disk diffusion
      test zone diameter relationship for a worldwide collection of Enterobacteriaceae
      enriched for extended-spectrum beta-lactamase-producing organisms.
AB  - To reassess the validity of existing susceptibility breakpoint criteria and to
      propose alternative breakpoint criteria for disk diffusion testing at lower
      susceptible MIC breakpoints, we analyzed a contemporary global collection of
      Enterobacteriaceae isolates (350) strains enriched for extended-spectrum beta
      lactamase (ESBL) producers (68 strains, 19.4%). The majority of the isolates
      (88.3% of the entire collection and 83.8% of the ESBL subset) were from
      bloodstream infections. Cefepime minimal inhibitory concentrations (MICs) were
      determined by broth microdilution methods and compared with the results obtained
      from disk diffusion testing for the entire collection of Enterobacteriaceae and
      for the ESBL subset alone. The regression coefficient was excellent for both
      scattergrams (r = 0.92-0.94). The intermethod categorical agreement remained
      excellent for the current breakpoints (susceptible at < or = 8 microg/mL or > or
      = 18 mm and resistant at > or = 32 microg/mL or < or = 14 mm) published by the
      National Committee for Clinical Laboratory Standards at 94.0%. The 2 alternative
      interpretive criteria considered at lower MIC breakpoints (i.e., susceptible as <
      or = 4 microg/mL and > or = 21 mm and susceptible as < or = 2 microg/mL and > or
      = 24 mm) did not compromise the intermethod test categorical accuracy, which
      remained excellent at 96.9% and 94.0%, respectively. Adopting the existing
      breakpoint criteria that remain accurate for ESBL-producing strains or any one of
      the above two alternative sets of breakpoint criteria analyzed would be
      acceptable, with excellent intermethod concordance between the MIC and disk
      diffusion results.

PMID- 15964497
TI  - Diagnosis of cerebral cryptococcoma using a computerized analysis of 1H NMR
      spectra in an animal model.
AB  - Viable cryptococci load in biopsy material from an animal model of cerebral
      cryptococcoma were correlated with 1H NMR spectra and metabolite profiles. A
      statistical classification strategy was applied to distinguish among high
      resolution 1H NMR spectra acquired from cryptococcomas, glioblastomas, and normal
      brain tissue. The overall classification accuracy was 100% when a genetic
      algorithm-based optimal region selection preceded the development of linear
      discriminant analysis-based classifiers. The method remained robust despite
      differences in the microbial load of the cryptococcoma group when harvested at
      different time points. These results indicate the feasibility of the method for
      diagnosis without isolation of the pathogenic microorganism and its potential for
      in vivo diagnosis based on computerized analysis of magnetic resonance spectra.

PMID- 15964498
TI  - Chemosusceptibility analysis of Plasmodium falciparum imported malaria in Italy.
AB  - A constant surveillance of susceptibility to antimalarials allows to optimize
      prevention and treatment of malaria in nonendemic countries. In vitro
      susceptibility of imported Plasmodium falciparum isolates to chloroquine,
      quinine, mefloquine, halofantrin, pyronaridine, and amodiaquine was analyzed by
      WHO Micro-test Mark III; IC50 and IC90 were calculated by WHO Log-probit. Sixty
      seven tests were performed. All the infections were acquired in Africa: 14.9% in
      East Africa and 85.1% in West Africa (WA). IC50 and IC90 (micromol/L) were
      chloroquine: 0.129 and 0.648; amodiaquine: 1.134 and 5.445; mefloquine: 0.38 and
      0.868; quinine: 0.193 and 0.478; halofantrin: 3.27 and 25.35; pyronaridine:
      11.504 and 51.996. Higher IC50 and IC90 were observed in East Africa versus West
      Africa strains. All strains were susceptible to quinine and mefloquine;
      chloroquine resistance, 14%; amodiaquine resistance, 33%, with cross-resistance
      to chloroquine (r = 0.93; P < .0001); halofantrin resistance, 3.6%, no cross
      resistance with chloroquine; low susceptibility to pyronaridine (66.7%), with
      cross-resistance with chloroquine (r = 0.38, P < 0.05). Lower levels of
      chloroquine resistance were observed in 2000-2003 as compared with prior data;
      thus, the reemergence of chloroquine susceptibility in Africa may be
      hypothesized.

PMID- 15964499
TI  - Clinical and economic impact of methicillin resistance in patients with
      Staphylococcus aureus bacteremia.
AB  - We performed a retrospective cohort study to determine the morbidity, mortality,
      and hospital costs attributable to methicillin resistance in patients with S.
      aureus bacteremia (SAB). Episodes of SAB occurring at the Detroit Receiving
      Hospital in 1999-2001 were evaluated. Controlling for confounding variables,
      patients with methicillin-resistant Staphylococcus aureus (MRSA) had a 1.5-fold
      longer length of stay (19.1 versus 14.2 days, P = 0.005) and a 2-fold increased
      cost of hospitalization (dollar 21577 versus dollar 11668, P = 0.001) compared
      with methicillin-susceptible S. aureus (MSSA). MRSA patients were at increased
      risk for delayed treatment, and delayed therapy was an independent predictor of
      mortality. Efforts should be made to ensure that appropriate therapy is initiated
      promptly in patients at risk for MRSA. Infection control policies must be
      strictly enforced to limit the spread of MRSA and potentially minimize excess
      hospital expenditures incurred with MRSA. With the advent of new treatment
      options, the impact of MRSA will need to be revisited to determine if these
      therapies can remedy the increased morbidity associated with MRSA.

PMID- 15964500
TI  - Pharmacodynamics of tobramycin in patients with cystic fibrosis.
AB  - Relationships between pharmacodynamic indices (PI), such as the area under the
      concentration-time curve (AUC)/MIC ratio and time > MIC (T(>MIC)), and efficacy
      have been described for antimicrobial drugs. The use of these quantitative
      relationships may increase the power to demonstrate significant effects of drugs,
      obviating the need to include large numbers in comparative trials. Patients with
      cystic fibrosis (CF) hospitalized for treatment of an infectious exacerbation due
      to Pseudomonas aeruginosa were eligible for the study. They received tobramycin
      3.3 mg/kg tid as initial therapy in combination with ticarcillin 125 mg/kg qid.
      Blood samples were drawn at t = 0-8 h after infusion. Pharmocokinetic parameters
      and PI were calculated for every individual and correlated to the relative
      improvement in forced expiratory volume during the first second (FEV1) and forced
      vital capacity (FVC) between pretreatment and days 9-11 as a measure of efficacy.
      The 3 PI fAUC/MIC, f Peak/MIC, and T(>MIC) of tobramycin showed a significant
      correlation with effect and was the highest for the fAUC/MIC relationships with
      FEV1 and FVC as determined both by the Emax model as well as Spearman
      correlations (r = 0.77, P = 0.002 and 0.58, P = 0.036 for FEV1 and FVC).
      Pharmacokinetic parameters AUC and Peak as such showed no significant correlation
      with effect, nor did the MIC values. There is a significant relationship between
      PI of aminoglycosides and efficacy parameter (increase in FEV1 and FVC) in
      patients with CF. This study demonstrates the applicability of pharmacodynamic
      relationships in determining efficacy of antimicrobial therapy, by demonstrating
      a strong PI-effect relationship in a group of only 13 patients.

PMID- 15964501
TI  - Therapeutic options among broad-spectrum beta-lactams for infections caused by
      levofloxacin-nonsusceptible Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae has consistently become more resistant to primary,
      orally administered treatment regimens used for community-acquired respiratory
      tract infections (CARTI; sinusitis, bronchitis, pneumonia). As resistance rates
      approach 40-50% in the United States and North America for penicillin and
      macrolides, other agents also have exhibited coresistance rates of 10-20%
      (tetracycline, clindamycin, trimethoprim/sulfamethoxazole). These facts led to
      altered clinical treatment guidelines (IDSA) supporting the use of respiratory
      fluoroquinolones (levofloxacin, gatifloxacin, gemifloxacin, and moxifloxacin).
      This report from the SENTRY Antimicrobial Surveillance Program lists possible
      parenterally administered treatment alternatives for the fluoroquinolone
      (levofloxacin)-nonsusceptible pneumococci. The SENTRY Program isolates from CARTI
      (1997-2003), totaling 21605 strains from Europe, Asia Pacific, and the Americas,
      were screened for fluoroquinolone-resistant S. pneumoniae. A total of 157 (0.7%)
      levofloxacin-nonsusceptible (MIC > or = 4 microg/mL) strains were identified and
      tested by reference broth microdilution methods against 27 antimicrobials.
      Quinolone resistance-determining region (QRDR) mutations were determined by PCR
      amplification and gene sequencing. The entire population of S. pneumoniae had the
      following antibiogram demographics: penicillin-nonsusceptible (32%), macrolide
      resistance (24%), tetracycline resistance (21%), clindamycin resistance (11%),
      trimethoprim/sulfamethoxazole resistance (33%), and 6% of strains were resistant
      to all 5 drugs. Levofloxacin-resistant strains routinely had 2 or more QRDR
      mutations most frequently in gyrA at Ser81Phe or Tyr and in parC at Ser79Phe or
      Tyr and Lys137Asn. Four agents had extremely low rates of resistance when tested
      against the 157 levofloxacin-nonsusceptible strains (e.g.,
      quinupristin/dalfopristin, 0% resistance; vancomycin, 0%; cefepime, 1%;
      ceftriaxone, 1%). Levofloxacin-nonsusceptible pneumococcal isolates remain
      uncommon, but are a growing problem in CARTI (1.4% in 2003), especially in
      previously fluoroquinolone-treated cases. Parenteral cephalosporins (cefepime or
      ceftriaxone) continue to be potent and safe for use in hospitalized patients with
      S. pneumoniae community-acquired pneumonia, used with or without co-drugs
      according to published guidelines.

PMID- 15964502
TI  - Investigation of the susceptibility trends in Japan to fluoroquinolones and other
      antimicrobial agents in a nationwide collection of clinical isolates: a
      longitudinal analysis from 1994 to 2002.
AB  - The susceptibilities of clinical isolates to fluoroquinolones (FQs) and other
      antimicrobial agents were surveyed to obtain an accurate understanding of the
      trends in incidence and antimicrobial resistance. The samples were collected from
      across Japan, biennially, between 1994 and 2002 and a defined level of resistance
      to FQ determined. Streptococcus pneumoniae and Haemophilus influenzae exhibited
      stable and high rates of susceptibility to FQ over the period examined. For
      methicillin-resistant Staphylococcus aureus the rate of resistance to FQ was 80%
      90%, markedly higher than that of methicillin-susceptible S. aureus. The rate of
      FQ-resistant Escherichia coli increased rapidly to approximately 10% for samples
      after 2000. Of 696 E. coli isolates collected in 2002, 13 produced an extended
      spectrum beta-lactamase (ESBL), with 6 of 13 ESBL-producing isolates being FQ
      resistant. No FQ resistance in clinical isolates of Salmonella spp. was detected
      in any of the surveys. The rate of FQ resistance to Pseudomonas aeruginosa
      isolated from urinary tract and respiratory tract infections was 40%-60% and 15%
      25%, respectively.

PMID- 15964503
TI  - Comparison of beta-lactams in counter-selecting resistance of Pseudomonas
      aeruginosa.
AB  - Suppression of resistance in a dense population of Pseudomonas aeruginosa has
      been shown with optimized quinolone exposures. However, relevance to the beta
      lactams is questionable because of the unknown impact of the inoculum effect. We
      explored the bactericidal activity of various beta-lactams and their propensity
      to suppress spontaneous resistance. Minimal killing and resistance selection was
      seen with piperacillin, most likely due to the inoculum effect. Moderate and
      significant killing was seen at 24 h with ceftazidime and meropenem,
      respectively; however, regrowth and selective resistance amplification was
      apparent at 48 h. Our results suggest that different beta-lactam subclasses have
      a distinct killing profile and propensity to suppress resistance against a dense
      population of P. aeruginosa. The pharmacodynamics of each subclass of agent
      should be examined individually, and investigations longer than 24 h may be
      necessary to fully evaluate the relationship between drug exposures and the
      likelihood of resistance suppression.

PMID- 15964504
TI  - Analysis of Clostridium difficile-associated diarrhea among patients hospitalized
      in tertiary care academic hospital.
AB  - The frequency of Clostridium difficile strains in stool samples of patients with
      diarrhea hospitalized in the hematology/oncology, surgery, orthopedics,
      transplantology ward, and emergency room of Davis Medical Center was analyzed. A
      total of 786 stool samples collected from patients with diarrhea and 180 samples
      taken from the hospital environment were cultured for C. difficile by routine
      methods. There were 119 strains of C. difficile isolated: 97 (12.3%) strains from
      patients' stools (no enteropathogen other than C. difficile was detected in these
      stool samples) and 22 (12.2%) strains from the hospital environment. It was
      confirmed that hospital environment plays an important role in transmission of C.
      difficile by AP-PCR and PCR ribotyping. Among 97 C. difficile strains isolated
      from patient' stools 25 were nontoxigenic (A-/B-), 67 were toxigenic (A+/B+), and
      5 strains were toxin B-positive/toxin A-negative. Analysis of concomitant
      symptoms among hospitalized patients with diarrhea demonstrated significantly
      longer duration of diarrhea caused by nontoxigenic strains than in cases of
      diarrhea caused by toxigenic strains. On the other hand, among patients infected
      by toxigenic strains, significantly higher leukocytosis and longer duration of
      fever were observed. The resistance of isolated C. difficile strains to
      erythromycin and clindamycin indicated the possibility of transmission in the
      hospital strains with macrolide-lincosamide-streptogramin B resistance type.

PMID- 15964505
TI  - Usefulness and influence of age of a novel rapid monoclonal enzyme immunoassay
      stool antigen for the diagnosis of Helicobacter pylori infection in children.
AB  - A novel rapid monoclonal enzyme immunoassay stool antigen for Helicobacter pylori
      detection (Immunocard STAT!HpSA, Meridian Diagnostic Inc , Cincinnati, OH) was
      evaluated in 29 infected and 99 noninfected children. The overall sensitivity,
      specificity, and positive and negative predictive values were 86.2%, 92.9%,
      78.1%, and 95.8%, respectively, with an accuracy of 91.4%. The highest
      performance was observed in children older that 10 years, with a sensitivity
      level of 100%, contrasting with a lower level, 75%, in those younger than 5
      years. A good negative predictive value was observed in all age groups,
      particularly in older children achieving 100%.

PMID- 15964506
TI  - Rates of nitric oxide dissociation from hemoglobin.
AB  - Nitric oxide (NO) plays a major role in human physiology and in many pathological
      states. Although oxyhemoglobin is known to destroy NO activity, NO activity can,
      in principle, be conserved through iron nitrosylation at vacant hemes. In order
      for this NO activity to be delivered, the NO must dissociate from the heme.
      Despite its study over the past few decades, our understanding of NO dissociation
      from hemoglobin is incomplete. In principle, there are at least four NO
      dissociation rates: kR(alpha), kR(beta), kT(alpha), and kT(beta), where the
      subscript refers to the quaternary state and the superscript to the hemoglobin
      chain. In the T-state, a proportion of the proximal histidine bonds break forming
      pentacoordinate alpha-nitrosyl hemoglobin. In vivo, alpha-nitrosyl hemoglobin
      predominates over beta-nitrosyl hemoglobin. In this study we have used a fast NO
      trap, Fe(II)-proline-dithiocarbamate, to measure NO dissociation rates from
      hemoglobin. We have varied solution conditions so the rate of dissociation from
      pentacoordinate alpha-nitrosyl hemoglobin could be definitively measured for the
      first time; kT(alpha) = 4.2 +/- 1.5 x 10(-4) s(-1). We have also found that the
      fastest NO dissociation rate is on the order of 10(-3) s(-1) and that NO
      dissociation from sickle cell hemoglobin is the same as that from normal adult
      hemoglobin.

PMID- 15964507
TI  - Pharmacogenomic profiling of an oxidative stress-mediated spongiform
      encephalopathy.
AB  - The majority of cellular superoxide is generated in the mitochondria as a by
      product of normal oxidative metabolism. In the mitochondria, superoxide is
      detoxified by manganese superoxide dismutase (SOD2). Mice lacking SOD2
      demonstrate a multifaceted neonatal lethal phenotype, including a spongiform
      encephalopathy that is preventable through antioxidant treatment. The molecular
      events behind the observed pathology in the cortex of these mice are unknown. We
      hypothesized that the lack of SOD2 would result in significant changes in
      cortical gene expression and that therapeutically beneficial antioxidant
      treatment would normalize the expression of some genes, providing insight into
      the mechanism by which mitochondrial oxidative stress results in
      neurodegeneration. We report the identification of gene expression profiles
      associated with this paradigm, which characterize the degree of response to the
      pharmacologic intervention. We have identified specific pathways targeted by
      endogenous oxidative stress, including glutathione metabolism, iron metabolism,
      and cell-survival pathways centering on the kinase AKT. The normalization of
      expression of some of these pathways by antioxidant treatment suggests approaches
      to treating disease in which endogenous oxidative stress plays a role.

PMID- 15964508
TI  - Determining the oxidation states of manganese in PC12 and nerve growth factor
      induced PC12 cells.
AB  - Excessive brain Mn can produce toxicity with symptoms resembling parkinsonism.
      This syndrome, called "manganism," correlates with loss of dopamine in the
      striatum and cell death in the striatum and globus pallidus. A common hypothesis
      is that cell damage in Mn toxicity is caused by oxidation of important cell
      components by Mn3+. Determination of the amount of Mn3+ present, under a range of
      conditions, in neuronal cells and brain mitochondria represents an important step
      in evaluating the "damage through oxidation by Mn3+ hypothesis." In an earlier
      paper we used X-ray absorption near-edge structure (XANES) spectroscopy to
      determine the amount of Mn2+ and Mn3+ in brain mitochondria under a range of
      conditions. Here we extend the study to investigate the evidence for formation of
      Mn3+ through oxidation of Mn2+ by ROS in PC12 cells and in PC12 cells induced
      with nerve growth factor (NGF) to display a phenotype more like that of neurons.
      Although the results suggest that very small amounts of Mn3+ might be present at
      low Mn levels, probably in Mn superoxide dismutase, Mn3+ is not stabilized by
      complex formation in these cells and therefore does not accumulate to detectable
      amounts.

PMID- 15964509
TI  - High oxygen radical production in patients with sporadic colorectal cancer.
AB  - It is hypothesized that excessive generation of reactive oxygen species (ROS) by
      phagocytes or leakage from mitochondria may harm key genes or proteins
      responsible for intestinal cell homeostasis. This may initiate the multistage
      process of colon cancer development. The present study investigates whether ROS
      production by whole blood may contribute to the etiology of colorectal cancer
      (CRC). Whole-blood oxygen radical production was measured by luminol-enhanced
      chemiluminescence and performed in fourfold with and without the stimuli phorbol
      12-myristate 13-acetate (PMA) and serum-treated zymosan (STZ). We evaluated
      patients (i) with a history of sporadic CRC at least 3 months after surgery, (ii)
      who were hereditary nonpolyposis colorectal cancer (HNPCC) gene carriers, and
      (iii) with familial adenomatous polyposis (FAP). For each patient group (n = 20)
      an age- and gender-matched healthy control group was measured. Unstimulated and
      PMA-stimulated values for maximal oxygen radical production were significantly
      higher in patients with sporadic CRC in comparison to controls (p = 0.01, p =
      0.04, respectively). Furthermore, trends toward higher unstimulated and PMA
      stimulated area under the curve chemiluminescence were seen in CRC patients
      compared with controls (p = 0.08, p = 0.09, respectively). In patients with HNPCC
      or FAP, unstimulated or PMA- or STZ-stimulated chemiluminescence did not differ
      compared to their control groups. In conclusion, whole-blood oxygen radical
      production was higher in patients with a history of sporadic CRC, in comparison
      with age- and gender-matched controls, which indicates that ROS may play a role
      in the etiology of sporadic CRC.

PMID- 15964510
TI  - Radical mediators and mitogen-activated protein kinase signaling in oxygen
      dependent radiosensitivity of human tumor cell lines.
AB  - Oxygen enhancement of tumor radiosensitivity is attributed to DNA damage by
      reactive oxygen species. The mechanism remains unclear but may involve
      mitochondria as major sources of oxygen and nitrogen radicals as well as central
      effectors of energy homeostasis and apoptosis. Here we used dihydrorhodamine and
      2',7'-dichlorodihydrofluorescein to compare mitochondrial and total cell
      generation, respectively, of reactive oxygen or nitrogen species in cells
      irradiated at 5 Gy. Irradiation in the presence of oxygen selectively stimulated
      mitochondrial radical production in HeLa and MeWo cells, but in MCF7 cells
      radical production was more generalized. In all three cell lines oxygen impaired
      cell proliferation as measured by resazurin reduction 7 days after irradiation.
      Antioxidants N-acetylcysteine, ascorbic acid, and melatonin largely prevented dye
      oxidation during normoxic irradiation yet had no effect on oxygen-dependent
      irradiation injury. However, NO synthase inhibitor N(G)-monomethyl-L-arginine
      protected HeLa and MCF7 though not MeWo cells, consistent with their different
      levels of constitutive NO generation. SB203580 inhibition of p38 MAPK appreciably
      protected HeLa and marginally protected MCF7 cells against oxygen-dependent
      irradiation injury, while the less specific JNK/SAPK inhibitor SP600125 and ERK
      inhibitor U0126 had no effect. None of the inhibitors affected MeWo
      radiosensitivity. Therefore oxygen-enhanced radiosensitivity in these tumor cell
      lines does not depend on extensive production of oxygen radicals and is cell-type
      dependent. NO mediates oxygen-dependent injury in HeLa and MCF7 cells, by p38
      dependent and MAPK-independent mechanisms, respectively. In MeWo cells this
      oxygen-enhanced radiosensitivity is independent of both NO and MAPK signaling.

PMID- 15964511
TI  - Long-term melatonin or 17beta-estradiol supplementation alleviates oxidative
      stress in ovariectomized adult rats.
AB  - Melatonin is an endogenously generated potent antioxidant. Our previous results
      indicated that melatonin improved learning and memory deficits in the transgenic
      mouse model of Alzheimer's disease (AD) and ovariectomized (OVX) rats by
      improving cholinergic nerve system dysfunction, preventing apoptosis. In this
      study we aim to investigate the antioxidative effects of melatonin or estradiol
      in the brains of ovariectomized rats. OVX Sprague-Dawley rats received daily
      injections of melatonin (5, 10, or 20 mg/kg), 17beta-estradiol (80 microg/kg), or
      sesame oil for 16 weeks. We found an increase in brain mitochondrial
      thiobarbituric acid-reactive substances (TBARS) levels, a decrease in
      mitochondrial glutathione (GSH) content as well as mitochondrial superoxide
      dismutase (SOD) activity and upregulation of the apoptotic-related factors, such
      as Bax, Caspase-3, and Prostate apoptosis response-4 (Par-4) in the frontal
      cortex of OVX rats. In addition to oxidative stress, OVX also caused decreased
      activities of mitochondrial respiration complex I and complex IV, which
      implicated mitochondrial dysfunction. Melatonin or 17beta-estradiol antagonized
      the detrimental effects induced by OVX. Furthermore, immunohistochemistry results
      revealed that the abnormal upregulation of the apoptotic related factor such as
      Bax, Caspase-3, and (Par-4) greatly reduced expression after melatonin or 17beta
      estradiol supplement action. These findings demonstrate the important effects of
      melatonin or 17beta-estradiol on postmenopausal neuropathy and support the
      potential application of melatonin in the treatment of dementia in postmenopausal
      women. Early, long-term melatonin application is a promising strategy which could
      potentially be applied in a clinical setting.

PMID- 15964512
TI  - Hypoxia-inducible factor 1 proteomics and diving adaptations in ringed seal.
AB  - The putative amino acid sequence of ringed seal (Phoca hispida) hypoxia-inducible
      factor 1alpha (HIF-1alpha) derived from DNA sequence analysis of the single-copy
      gene has been investigated. The rationale for these studies was to determine the
      reasons for the presence of HIF-1alpha at relatively high levels in seal tissues,
      and its possible role in protection against diving-related oxidative damage.
      Sequence analysis indicated that the bHLH/PAS and TAD functional domains are very
      similar to those in terrestrial mammals, although there were significant sequence
      differences between the mouse and seal proteins in a region of the ODD domain.
      Some of these results indicate that seal HIF-1alpha protein can bind HIF-Ibeta,
      DNA, transcriptional coactivators, and von Hippel-Lindau protein (pVHL). The
      presence of HIF-1alpha in seal tissues was not related to the absence of pVHL,
      which was found to be present in all seal tissues examined. It is concluded that
      seal HIF-1alpha may act as a transcriptional activator and that its presence in
      seal tissues is probably not caused by its inability to interact with pVHL. It is
      suggested that seal HIF-1 may serve two functions in the postdiving period,
      namely, to attenuate ischemia/reperfusion-induced oxidative stress and to allow
      efficient lung reinflation.

PMID- 15964513
TI  - Lung epithelial cells release ATP during ozone exposure: signaling for cell
      survival.
AB  - The common air pollutant ozone causes acute toxicity to human airways. In primary
      and transformed epithelial cells from all levels of human or rat airways, ozone
      levels relevant to air pollution (50-200 ppb) increased extracellular [ATP]
      within 7-30 min. A human bronchial epithelial cell line (16HBE14o(-)) that forms
      electrically resistant polarized monolayers had up to 10-fold greater apical than
      basolateral surface extracellular [ATP] within 7 min of ozone exposure. Increased
      extracellular [ATP] appeared due to ATP secretion or release because (1)
      inhibition of ectonucleotidase (cell surface enzyme(s) which degrade ATP) by
      ozone did not occur until >120 min of ozone exposure and (2) brefeldin A, a
      secretory inhibitor, eliminated elevation of extracellular [ATP] without
      affecting intracellular ATP. Extracellular ATP protected against ozone toxicity
      in a P2Y receptor-dependent manner as (1) removal of ATP and adenosine by apyrase
      and adenosine deaminase, respectively, potentiated ozone toxicity, (2)
      extracellular supplementation with ATP, a poorly hydrolyzable ATP analog
      ATPgammaS, or UTP inhibited apoptotic and necrotic ozone-mediated cell death, and
      (3) ATP-mediated protection was eliminated by P2 and P2Y receptor inhibitors
      suramin and Cibacron blue (reactive blue 2), respectively. The decline in glucose
      uptake caused by prolonged ozone exposure was prevented by supplemental
      extracellular ATP, an effect blocked by suramin. Further, Akt and ERK
      phosphorylation resulted from exposure to supplemental extracellular ATP. Thus,
      extracellularly released ATP signals to prevent ozone-induced death and
      supplementation with ATP or its analogs can augment protection, at least in part
      via Akt and /or ERK signaling pathways and their metabolic effects.

PMID- 15964514
TI  - Induction of heme oxygenase 1 by moderately oxidized low-density lipoproteins in
      human vascular smooth muscle cells: role of mitogen-activated protein kinases and
      Nrf2.
AB  - Oxidized low-density lipoproteins (LDL) play a central role in atherogenesis and
      induce expression of the antioxidant stress protein heme oxygenase 1 (HO-1). In
      the present study we investigated induction of HO-1 and adaptive increases in
      reduced glutathione (GSH) in human aortic smooth muscle cells (SMC) in response
      to moderately oxidized LDL (moxLDL, 100 microg protein/ml, 24 h), a species
      containing high levels of lipid hydroperoxides. Expression and activity of HO-1
      and GSH levels were elevated to a greater extent by moxLDL than highly oxidized
      LDL but unaffected by native or acetylated LDL. Inhibitors of protein kinase C
      (PKC) or mitogen-activated protein kinases (MAPK) p38(MAPK) and MEK or c-jun-NH2
      terminal kinase (JNK) significantly attenuated induction of HO-1. Phosphorylation
      of p38(MAPK), extracellular signal-regulated kinase (ERK1/2), or JNK and nuclear
      translocation of the transcription factor Nrf2 were enhanced following acute
      exposure of SMC to moxLDL (100 microg protein/ml, 1-2 h). Pretreatment of SMC
      with the antioxidant vitamin C (100 microM, 24 h) attenuated the induction of HO
      1 by moxLDL. Native and oxidized LDL did not alter basal levels of intracellular
      ATP, mitochondrial dehydrogenase activity, or expression of the lectin-like
      oxidized LDL receptor (LOX-1) in SMC. These findings demonstrate for the first
      time that activation of PKC, p38(MAPK), JNK, ERK1/2, and Nrf2 by oxidized LDL in
      human SMC leads to HO-1 induction, constituting an adaptive response against
      oxidative injury that can be ameliorated by vitamin C.

PMID- 15964515
TI  - ESR spin trapping of a carbon-centered free radical from agonist-stimulated human
      platelets.
AB  - Several free radical intermediates formed during synthesis of prostaglandin H
      synthase (PGHS) catalyze the biosynthesis of prostaglandins from arachidonic acid
      (AA). We attempted to directly detect free radical intermediates of PGHS in
      cells. Studies were carried out using human platelets, which possess significant
      PGHS activity. Electron spin resonance (ESR) spectra showed a g = 2.005 signal
      radical, which was formed by the incubation of collagen, thrombin, AA, and a
      variety of peroxides with human platelets. The ESR spectra obtained using 5,5
      dimethyl-1 pyrroline N-oxide (DMPO) and alpha-phenyl N-tert.-butylnitron (PBN)
      were typical of an immobilized nitroxide. Extensive Pronase digestion of both the
      DMPO and PBN adducts allowed us to deduce that it was a carbon-centered radical.
      The formation of this radical was inhibited by potassium cyanide and by
      desferroxamine. Peroxides stimulated formation of the g = 2.005 signal radical
      and inhibited platelet aggregation induced by AA. PGHS cosubstrates increased the
      intensity of the radical signal but inhibited platelet aggregation induced by AA.
      Both S-nitro-L-glutathione and reduced glutathione quenched the g = 2.005 radical
      but could not restore platelet aggregatory activity. These results suggest that
      the carbon-centered radical is a self-destructing free radical formed during
      peroxide-mediated deactivation of PGHS in human platelets.

PMID- 15964516
TI  - A new method for monitoring nitric oxide production using Teflon membrane
      microdialysis.
AB  - The measurement of nitric oxide (NO) by electron spin resonance (ESR) is
      complicated by potentially toxic spin-trapping agents, which may affect the NO
      producing cells per se and/or cause artifacts and systemic side effects. These
      problems can be addressed by preventing direct interaction between the agent and
      the biological system. In the present study, we utilized Teflon as a barrier
      between the spin trap and the living cell, since the material is permeable to gas
      only. Our aim was to investigate if NO could diffuse across the membrane in
      sufficient amounts to be trapped and quantified by ESR. We used standard
      microdialysis equipment and specially designed dialysis probes, or tubing, with
      Teflon membranes. Sodium nitroprusside was used as a NO donor and Fe-N
      dithiocarboxysarcosine (Fe(DTCS)2) as a spin trap. NO readily diffuses through
      Teflon and could be quantified in concentrations considerably below 50 nM in a
      reproducible and accurate manner. In cell cultures of activated murine
      macrophages, NO synthesis from iNOS could be monitored and we noted a huge
      increase in NO concentration by superoxide dismutase. We conclude that spin
      trapping of NO by Fe(DTCS)2 across Teflon membranes is an attractive approach for
      quantifying and monitoring nitric oxide production without interfering with cell
      viability.

PMID- 15964517
TI  - Human NAD(P)H:quinone oxidoreductase inhibition by flavonoids in living cells.
AB  - Procedures for assessing enzyme inhibition in living cells are an important tool
      in the study of the relevance of enzyme-catalyzed reactions and interactions in
      the human body. This paper presents the effects of flavonoids on NAD(P)H:quinone
      oxidoreductase 1 (NQO1) activity, by a newly developed method to measure NQO1
      inhibition in intact cells. The principle of this method is based on the
      resorufin reductase activity of NQO1. The change in fluorescence in time was used
      to determine NQO1 activity in intact Chinese hamster ovary (CHO) cells
      genetically engineered to overexpress human NQO1. Applying this method to
      determine the inhibitory effects of reported in vitro NQO1 inhibitors
      (dicoumarol, 7,8-dihydroxyflavone, chrysin) showed that for all inhibitors
      tested, the IC50 in intact cells was at least 3 orders of magnitude higher than
      the IC50 in cell lysates. This result demonstrates that in vitro studies with
      purified NQO1 or with extracts from disrupted tissues are of limited value for
      obtaining insight into the situation in living cells. Possible factors underlying
      this discrepancy are being discussed. For the first time, we determined NQO1
      inhibition by flavonoids in cells without disruption of the cells or addition of
      cofactors, enabling the assessment of enzymatic activity and the interaction of
      modulators of enzymatic activity in an intracellular situation.

PMID- 15964518
TI  - Vitamin D sensitizes breast cancer cells to the action of H2O2: mitochondria as a
      convergence point in the death pathway.
AB  - Calcitriol, the hormonal form of vitamin D3, sensitizes breast cancer cells to
      reactive oxygen species (ROS)-dependent cytotoxicity induced by various
      anticancer modalities. This effect could be due to increased generation of ROS
      and/ or to increased sensitivity of the target cells to ROS. This work examined
      the effect of calcitriol on the damage inflicted on breast cancer cells by the
      direct action of ROS represented by H2O2. Treatment of MCF-7 cells with H2O2
      resulted in activation of caspase 7 as well as induction of caspase-independent
      cell death. Both were enhanced by 48-72 h of pretreatment with calcitriol. This
      effect was not due to modulation of H2O2 degradation or to a specific effect on
      *OH-mediated cytotoxicity. The H2O2-induced drop in mitochondrial membrane
      potential and release of cytochrome c were enhanced by calcitriol. These findings
      indicate that calcitriol sensitizes breast cancer cells to ROS-induced death by
      affecting event(s) common to both caspase-dependent and -independent modes of
      cell death upstream to mitochondrial damage.

PMID- 15964519
TI  - Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with
      lipoic and dihydrolipoic acid.
AB  - Alpha-lipoic acid (LA) and dihydrolipoic acid (DHLA) may have a role as
      antioxidants against nitric oxide-derived oxidants. We previously reported that
      peroxynitrite reacts with LA and DHLA with second-order rate constants of 1400
      and 500 M(-1) s(-1), respectively, but indicated that these direct reactions are
      not fast enough to protect against peroxynitrite-mediated damage in vivo.
      Moreover, the mechanism of the reaction of peroxynitrite with LA has been
      recently challenged (J. Biol. Chem.279:9693-9697; 2004). Pulse radiolysis studies
      indicate that LA and DHLA react with peroxynitrite-derived nitrogen dioxide
      (*NO2) (k2 = 1.3 x 10(6) and 2.9 x 10(7) M(-1) s(-1), respectively) and carbonate
      radicals (CO(3-)) (k2 = 1.6 x 10(9) and 1.7 x 10(8) M(-1) s(-1), respectively).
      Carbonate radical-mediated oxidation of LA led to the formation of the potent one
      electron oxidant LA radical cation. LA inhibited peroxynitrite-mediated nitration
      of tyrosine and of a hydrophobic tyrosine analog, N-t-BOC L-tyrosine tert-butyl
      ester (BTBE), incorporated into liposomes but enhanced tyrosine dimerization.
      Moreover, while LA competitively inhibited the direct oxidation of glutathione by
      peroxynitrite, it was poorly effective against the radical-mediated thiol
      oxidation. The mechanisms of reaction defined herein allow to rationalize the
      biochemistry of peroxynitrite based on direct and free radical-mediated processes
      and contribute to the understanding of the antioxidant actions of LA and DHLA.

PMID- 15964520
TI  - Antioxidant enzyme activity is up-regulated after unilateral resistance exercise
      training in older adults.
AB  - Cellular antioxidant capacity and oxidative stress are postulated to be critical
      factors in the aging process. The effects of resistance exercise training on the
      level of skeletal muscle oxidative stress and antioxidant capacity have not
      previously been examined in older adults. Muscle biopsies from both legs were
      obtained from the vastus lateralis muscle of 12 men 71 +/- 7 years of age.
      Subjects then engaged in a progressive resistance exercise-training program with
      only one leg for 12 weeks. After 12 weeks, the nontraining leg underwent an acute
      bout of exercise (exercise session identical to that of the trained leg at the
      same relative intensity) at the same time as the last bout of exercise in the
      training leg. Muscle biopsies were collected from the vastus lateralis of both
      legs 48 h after the final exercise bout. Electron transport chain enzyme activity
      was unaffected by resistance training and acute resistance exercise (p < 0.05).
      Training resulted in a significant increase in CuZnSOD (pre--7.2 +/- 4.2, post-
      12.6 +/- 5.6 U.mg protein(-1); p = 0.02) and catalase (pre--8.2 +/- 2.3, post-
      14.9 +/- 7.6 micromol.min(-1).mg protein(-1); p = 0.02) but not MnSOD activity,
      whereas acute exercise had no effect on the aforementioned antioxidant enzyme
      activities. Furthermore, basal muscle total protein carbonyl content did not
      change as a result of exercise training or acute exercise. In conclusion,
      unilateral resistance exercise training is effective in enhancing the skeletal
      muscle cellular antioxidant capacity in older adults. The potential long-term
      benefits of these adaptations remain to be evaluated.

PMID- 15964521
TI  - [How pediatric residents involve children during medical decision-making?].
AB  - OBJECTIVE: To describe how pediatric residents involve children during medical
      decision-making and evaluate the relationship between practice patterns and
      residents characteristics. POPULATION AND METHODS: We conducted a prospective
      multicenter anonymous written survey. Self-reported involvement of children by 45
      French pediatric residents in practice pattern was collected and analysed.
      RESULTS: Most residents reported they informed patients in more than 50% of the
      cases (82%). Only a minority of the residents asked for consent, respected
      children refusal or presented other choices to the treatment. The main reasons
      that explain the lack of partnership are children incompetence and the medical
      situation. No statistically significant relationship between practice patterns
      and residents characteristics was found. CONCLUSIONS: Partnership with children
      varies across residents and according to the level of involvement considered. No
      statistical differences were obtained to explain variations between residents'
      attitude toward involvement of children. Nevertheless medical education in ethics
      or decision-making could increase partnership with children.

PMID- 15964522
TI  - [Neonatal outcome after exposure to selective serotonin reuptake inhibitors late
      in pregnancy].
AB  - OBJECTIVES: To analyse neonatal effects after in utero selective serotonin
      reuptake inhibitors exposure and the pertinence of recommendations delivered by
      our team. MATERIALS AND METHODS: We report a series of 27 pregnancies exposed
      late in pregnancy including the period of delivery, to the Selective Serotonin
      Reuptake Inhibitors (SSRI) and having been the subject of a call to the Regional
      Center of Pharmacovigilance of Tours (CRPV). RESULTS: Twenty-seven children were
      born without malformation. Twelve children were hospitalized because of
      prematurity (two), exposure to other drugs imposing particular surveillance
      (eight) or in view of abnormal neonatal effects (two). Five newborns (18.5%) of
      which three had also been exposed to other drugs (benzodiazepine, neuroleptic, H1
      antagonist) had presented one or more neonatal adverse effects compatible with
      the role of the SSRI (irritability, agitation, shivering, hypotonia) but with
      uncertainty about a clear discrimination between withdrawal syndrome and
      serotonin impregnation. All the symptoms disappeared spontaneously. One of the
      five children had a described in treated adults but two neonatal observations
      were published. No child had hemorrhagic symptoms as described in treated adults
      despite the fact that two neonatal observations were reported. CONCLUSION: This
      study confirms the relative benignity of SSRI exposure during late pregnancy. Our
      recommendations for monitoring the newborns during their stay in maternity wards
      were well respected. The risk of hemorrhagic symptoms or hyponatremia, not well
      known by pediatricians, deserves to be recalled to medical teams who take in
      charge newborns exposed to SSRI.

PMID- 15964523
TI  - [2001 national survey of nosocomial infection prevalence among newborns and under
      eighteen children and adolescents in France].
AB  - OBJECTIVES: To know nosocomial infections (NI) rates among newborns and
      hospitalised children according to age and units of hospitalisation, METHODS: In
      2001, the Comite technique des infections nosocomiales (CTIN) initiated a one-day
      prevalence survey on an arranged date. It was conducted by the 5 centres de
      coordination de lutte contre les infections nosocomiales (C.CLIN). Paediatric
      data only were analysed dividing them into 2 groups: newborns (NB) up to 28 days
      old, whether in maternity, neonatology or intensive care units, and children (CH)
      from 29 days to 18 years old with separate analysis for surgery, cancer units and
      intermediate care and rehabilitation centres (ICRC). RESULTS: The survey included
      21 596 children under 18 years old: 9136 NB and 12,460 CH, i.e. 7.1% of the total
      hospital population on that one given day. A total of 2.6% of the patients were
      infected, with 1.2% of NB and 3.3% of CH. There were 1.09 infections per patient.
      456 different microorganisms were responsible for 562 infections, i.e. 81.1%:
      18,6% Staphylococcus aureus of which 26.7% were methicillin resistant (MRSA),
      21.9% Staphylococcus epidermis, 21.9% enterobacteries, 10.3% Pseudomonas
      aeruginosa, 4.4% Candida albicans, and 4.2% rotavirus. NB and CH infection
      factors were studied separately. Selective criteria for hospitalised NB were:
      gender: male(P < 0.05), level of gravity (P < 0.05), surgery (P < 0.001),
      catheter (P < 0.01) and hospital type (P < 0.01). For EN, criteria were severity
      score (P < 0.01), surgery (P < 0.001), catheter (P < 0.01), and hospital type (P
      < 0.01). The rate for patients hospitalised in cancer units was 13.2% with no
      significant factors found. The rate of infected patients in intensive care units
      was 7.8% for NB and 16.2% for CH, with 9.6% neonatal, 30.8% heart condition,
      26.3% non-specialised units and 14.2% children units. ICRC infection rate was
      4.5% while surgery units had a rate of 1.9% with 2.4% orthopaedic, 0.7% children
      units, 2.0% non-specialised units and 8.1% neurosurgery. DISCUSSION: The 2001 NI
      level showed a significant fall from 3.5% in the 1996 survey (all ages) to 2.4%.
      However, including newborns from private maternity units into the survey may have
      partly lowered this level. MRSA levels have also dropped from 46% in 1996 to 27%
      in 2001. It is difficult to compare international data as definitions vary.
      Furthermore, it should be possible to separate newborns from older children as
      well as specifying the type of units involved. Infected patients levels are
      generally lower in the French surveys, no matter the age group or units studied
      than in other surveys. CONCLUSION: This survey has enabled the monitoring of the
      children population in maternity units, on a given day, in France. It showed that
      the rate of NI in the paediatric population seems low compared to previous data
      or other countries'data. Efforts need to be made in order to lower it further.
      Incidence surveillance method is preferable to single out which risk factors can
      be acted upon. Standardized national protocols are offered to maternity units and
      should soon be available for newborns units as well as older children units.

PMID- 15964524
TI  - [Which alternative method to dual-energy X-ray absorptiometry for assessing body
      composition in overweight and obese adolescents?].
AB  - CONTEXT: Professionals in charge of overweight and obese children and adolescents
      need a simple, reliable and precise method for assessing body composition.
      OBJECTIVES: To compare body composition as assessed by dual-energy X-ray
      absorptiometry (DXA), bioelectrical impedance analysis (BIA) and the skinfold
      thickness (SFT) method in overweight and obese adolescents, and to establish and
      validate new predictive equations of body composition from BIA measurements using
      DXA as standard method. SUBJECTS AND METHODS: Body composition was assessed in
      143 obese adolescents (Z-score = 3.2 +/- 1.4) aged 12 to 17 years by DXA, BIA
      (RJL System, Analycor and Analycor XF models) and SFT (Siri and Slaughter's
      equations). New prediction equations of fat mass (FM) as assessed by DXA were
      computed from BIA measurements in a calibration group, and validated in an
      homologous group of subjects. Results. - The Bland-Altman test showed that
      compared to DXA, BIA underestimated FM by 2.8 +/- 2.0 kg and 2.3 +/- 2.1 kg using
      the RJL System and Analycor impedancemeter, respectively (P < 0.001). With the
      Analycor XF model, FM was underestimated by 3.3 +/-2.6 kg in boys, and over
      valued by 0.6 +/- 2.4 kg in girls. On the contrary, the predictive equation of
      Wabitsch et al. overvalued FM by 6.2 +/- 2.9 kg. The SFT method overvalued FM by
      2.1 +/- 5.0 kg in boys and underestimated FM by 2.3 +/- 3.5 kg in girls using
      Slaughter et al. equation, while Siri's equation underestimated FM by 4.0 +/- 2.9
      kg (P < 0.001). The alternative to the DXA method to assess FM was BIA with new
      prediction equations including gender, body weight, height(2)/resistance and
      reactance. CONCLUSION: DXA, BIA and the SFT method were not directly
      interchangeable. The SFT method was inadequate to assess body composition in
      overweight and obese adolescents. BIA and new prediction equations could be an
      alternative to the DXA method in overweight and obese adolescents.

PMID- 15964525
TI  - [First-line liposomal amphotericin B for pediatric visceral leishmaniasis in
      southern France].
AB  - AIMS OF THE STUDY: First, to describe liposomal amphotericin B (AmBisome use as
      first line treatment of pediatric visceral leishmaniasis and secondly, to
      evaluate the incidence of the disease in southern France (Provence - Alpes - Cote
      d'Azur - Corse). MATERIAL AND METHODS: Retrospective chart review of children
      referred for visceral leishmaniasis from 1996 to 2003. RESULTS: Thirty-two
      children under 15 years of age and suffering from visceral leishmaniasis were
      treated with liposomal amphotericin B as first line treatment. Clinical and
      biological features were usual: age <5 years, no immunodeficiency, spleen
      enlargement and fever, cytopenia. In this population, treatment effectiveness was
      evaluated to 97% (one relapse). Under treatment, patients quickly improved. Drug
      regimens varied from 18 to 24 mg/kg (day 1 to 5, and day 10). Four other children
      were not treated with first-line liposomal amphotericin B during the period.
      Thus, the incidence of pediatric visceral leishmaniasis was evaluated to be
      0.61/100,000 children <15 years/year in the region (2.74 in the Alpes-Maritimes
      department, French Riviera, and 0.6 in the Bouches-du-Rhone department,
      Marseilles area). CONCLUSION: Liposomal amphotericin B treatment is usual for
      children referred for visceral leishmaniasis in this region. This treatment may
      be approved regarding the high level of effectiveness and the low number of
      adverse events. A two days drug regimen with 20 mg/kg should be evaluated.
      Moreover, the incidence of the pediatric visceral leishmaniasis in southern
      France is decreasing, but local variations may be observed.

PMID- 15964526
TI  - [Lethal aortic dissection in a 13-year-old boy with a vascular Ehlers-Danlos
      syndrome].
AB  - Vascular Ehlers-Danlos syndrome(EDS) is at high risk of death by arterial
      rupture. CASE REPORT: A 13-year-old boy with vascular EDS and aortic dissection
      was admitted in pediatric emergency care unit. The children died after surgery by
      massive hemorrhage and prosthetic rupture. DISCUSSION: The precocity of this
      vascular accident EDS is uncommon. It occurred despite clinical and
      echocardiographic follow-up. The death of the children confirmed the difficulties
      in surgery of vascular manifestation, even if appropriate and rapid management
      was already done. CONCLUSION: Patients with vascular EDS must be identified
      because of its lethal complications. Friability of the vessels makes surgical
      treatment difficult. A trial using beta blockers therapy is ongoing.

PMID- 15964527
TI  - [Disseminated fusarium infection in two neutropenic children].
AB  - Disseminated fusariosis in children is a rare and serious fungal infection, that
      occurs especially in neutropenic immunosuppressed patients, treated for malignant
      hemopathy, or bone marrow transplant recipient. Treatment is difficult and
      mortality is estimated between 50 and 70% in adult patients. CASE REPORT 1: A ten
      year-old boy, treated for an acute lymphoblastic leukemia in second relapse,
      presented a disseminated fusarium spp infection, that occurred during
      neutropenia. He died due to fusariosis infection in spite of amphotericin B
      treatment. CASE REPORT 2: A ten-year-old neutropenic girl, treated for an acute
      myeloid leukemia, presented disseminated fusariosis, uncontrolled by amphotericin
      B. Recovery was observed after voriconazole introduction and resolution of
      neutropenia. Ten months later, she presented a leukemia's relapse, treated by new
      intensive chemotherapy with secondary prophylaxis by voriconazole, without
      fusariosis's recurrence. CONCLUSION: Voriconazole, a new triazole agent, seems to
      be an alternative antifungal agent to amphotericin B for disseminated fusarium
      infection, either at the acute phase or for secondary prophylaxis.

PMID- 15964528
TI  - [Treatment with metyrapone of Cushing's syndrome revealing McCune-Albright
      syndrome].
AB  - Cushing's syndrome reveals McCune-Albright syndrome in a minority of patients.
      Bilateral adrenalectomy is performed on the majority of cases. CASE REPORT: We
      present a case of McCune-Albright syndrome revealed by a Cushing's syndrome
      treated by metyrapone. Results were good, after a 4-year follow up. CONCLUSION:
      Treatment with metyrapone could be recommended, for some patients, in McCune
      Albright syndrome with Cushing's syndrome before chirurgical treatment.

PMID- 15964529
TI  - [A twelve-year-old teenager with bone pain and white papules].
AB  - Here we present a case report in which a teenager, with papules on the arm and
      back since the infancy, complained of back and right knee pain at the age of 12
      years. The radiological examination led to the diagnosis of osteopoikilosis and
      melorheostosis. The Buschke-Ollendorff syndrome (BOS) associates osteopoikilosis
      (asymptomatic bone dysplasia) and disseminated dermatofibrosis. The BOS is rare,
      and its association with melorheostosis (another bone dysplasia in which pain and
      deformity may occur) makes the prognosis uncertain. This case report highlights
      the diagnosis problems related with bone pain in paediatrics. The purpose of this
      manuscript is to present the characteristics of two bone dysplasias:
      osteopoikilosis and melorheostosis, and to discuss the involvement of each one in
      the clinical picture of our patient.

PMID- 15964530
TI  - [Spinal bone tumors in children].
AB  - The occurrence of back pain in children and adolescents varies from 30 to 51% in
      the literature. Bone tumors can be responsible for back pain. This paper presents
      the more common spinal bone tumors in children and adolescents, and specifies
      their etiology, their natural history, and their treatment as well.

PMID- 15964531
TI  - [Technical aspects and relevance of energy expenditure and physical activity
      assessment in clinical research for cystic fibrosis patients].
AB  - Cystic fibrosis (CF) is characterized by deteriorating lung function and mal
      digestion, which result in growth failure and/or under-nutrition. Several
      factors, alone or combined, contribute to malnutrition in CF: poor energy intake,
      elevation of energy loss as a result of malabsorption, increasing resting energy
      expenditure due to genetic mutation and/or pulmonary exacerbation. Several
      techniques have been used to assess energy expenditure and physical activity in
      order to better understand mechanisms of malnutrition in CF and follow
      therapeutic interventions. Indirect calorimetry (IC) studies have shown that
      resting energy expenditure (REE) was 10-22% higher than predictive values. This
      increase could be attributed to chronic inflammation as a result of Pseudomonas
      aeruginosa (PA) infection. Indeed, intravenous antibiotic therapy decreases REE.
      Doubly labelled water technique and heart rate monitoring calibrated against IC
      techniques shows that total energy expenditure (TEE) was not different than in
      healthy children. Physical activity level assessed by the ratio TEE-REE is also
      not different between CF of healthy children. Recently, new accelerometry
      technics, easier to use and less invasive have been successfully used in order to
      assess physical activity level in CF. Precise and ambulatory assessment of energy
      expenditure and physical activity permit to check and adapt dietary allowances in
      CF. These techniques could be simultaneously used and be helpful to assess
      efficacy of intervention studies.

PMID- 15964532
TI  - [The fetal alcohol syndrome and congenital absence of one kidney].

PMID- 15964533
TI  - [Attention deficit and hyperactivity disorder or multiplex developmental
      disorders in child? Let us be sure...].
AB  - Personality disorders in child can be easily confused -- initially at least --
      with Attention Deficit and Hyperactivity Disorder (ADHD). Because of the
      therapeutic and prognostic stake related to the early psychiatric care of Child
      Developmental Personality Disorders it is important to sensitize pediatric and
      general practitioner with the clinical screening of these disorders. Indeed any
      premature prescription of psychostimulant treatment in these children can have
      regrettable consequences on their psychic functioning already precarious.

PMID- 15964534
TI  - [Fat-soluble vitamins in infants].
AB  - Vitamins are micronutrients not synthesised by the human body and should be
      provided by the nutrition. Liposoluble vitamins include vitamins A, E, D and K.
      Vitamins A and E are two potent antioxidant nutrients and play a significant role
      in immune function. Vitamin D plays a major role in intestinal calcium absorption
      and bone mineralization. Vitamin K intervenes in the synthesis of coagulation
      factors particularly in the prothrombin synthesis. Vitamin metabolism, placental
      transfer, vitamin status in newborns and infants are reported. Finally
      requirements of these vitamins are defined.

PMID- 15964535
TI  - [The polyols in pediatric dentistry: advantages of xylitol].
AB  - Sugars ingested outside of meals play an important role in the etiology of
      caries. In this respect, sugar substitutes present a very interesting
      alternative. In addition to the recommendations and usual care to their patients,
      dental surgeons also have to inform them on a dietetic level. Chewing sugar-free
      chewing gum after any light meal when it is not followed by a brushing presents a
      real interest. The authors describe the different polyols and their respective
      uses. Polyols are widely found in foodstuffs (sweets, chewing-gum, biscuits,
      cooked meals for diabetic), pharmaceutical products (syrups, pastilles to be
      sucked, various medicines), non-pharmaceutical chemists (toothpastes, mouth
      washes...). By the light of the most recent published works, the particular
      properties of xylitol are described. Polyols are more particularly indicated for
      sugar-eater or sick children (syrups), and for those carrying a hight risk of
      developing caries (progressive polycaries, hyposialie...). Therefore polyols are
      not only a means of stabilizing some pathologies (diabetes, obesity) but also a
      weapon in the prevention of dental caries.

PMID- 15964536
TI  - Cigarette smoking may reduce plasma leptin concentration via catecholamines.
AB  - BACKGROUND: Leptin might influence body weight among smokers. DESIGN: (A)
      Screening of plasma leptin levels in 222 sedentary, smoking and non-smoking
      middle-aged men. (B) Double-blind, placebo-controlled smoking intervention on
      smokers (n=31). (C) Non-smokers (n=40) received chewing gum with nicotine (2mg
      nicotine, n=23) or without nicotine (n=19). (D) The effects of nicotine (0.05 and
      0.5 microg/mL) were monitored on leptin secretion and mRNA levels in a human
      placental cell line (BeWo) expressing leptin, a murine adipocyte cell line (3T3
      L1) and human adipose tissue explants. RESULTS: (A) Plasma leptin levels in
      smoking men (8.4+/-8.4 ng/mL, n=100) was lower as compared to non-smokers (10.3+/
      7.3 ng/mL, n=122) (P<0.001), even when adjusted for differences in body mass
      index (BMI) (P<0.001). (B) A significant reduction (P=0.02) in plasma
      concentration of leptin was found already after smoking one cigarette.
      Concomitant with the 3-5 fold increase in plasma nicotine concentration after the
      first cigarette, we observed increased plasma adrenaline levels (P=0.005). (C)
      There was no effect of nicotine on plasma leptin levels in non-smokers receiving
      nicotine-containing chewing gum, and plasma concentrations of catecholamines were
      unaltered. (D) There was no effect of nicotine on leptin mRNA expression after
      incubation with cells or adipose tissue. CONCLUSION: Cigarette smoking reduced
      plasma leptin concentration in vivo, whereas nicotine had no direct effect on
      leptin expression in vitro. Nicotine might indirectly reduce leptin secretion via
      enhanced plasma catecholamine concentration.

PMID- 15964537
TI  - HAART with didanosine once versus twice daily: adherence and efficacy.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) containing didanosine
      taken twice daily was compared with HAART containing didanosine taken once daily
      in terms of adherence and efficacy. METHOD: This was a self-controlled
      prospective cohort study, carried out in a tertiary level hospital. A total of 49
      HIV-infected patients were included. They were prescribed HAART according to
      guidelines. After six months taking HAART containing didanosine twice daily,
      patients continued with the same regimen of HAART although once daily. Thereafter
      they were followed up for a further nine months. Adherence and virological
      efficacy were assessed at three-month intervals, for a total of six times, in
      every patient. RESULTS: Overall, adherence was poor, with only 19 patients (39%)
      showing adequate adherence for all six visits. Adequate adherence was observed in
      29 patients (59%) three months before didanosine switching, and in 37 patients
      (75%) three months after didanosine switching (P=0.034). Pooled HIV RNA results
      of the first three visits were higher than the same results of the last three
      visits (P=0.05). CONCLUSIONS: Non-adherence is common among patients who take
      HAART. Simplification of regimens is useful to improve adherence and efficacy.

PMID- 15964538
TI  - Tuberculous brain abscess in AIDS patients: report of three cases and literature
      review.
AB  - OBJECTIVE: Clinical description of tuberculous brain abscess in patients with
      acquired immunodeficiency syndrome (AIDS). METHODS: Clinical case report and
      review of the literature from January 1981 to January 2003 using the MEDLINE
      database. RESULTS: The authors report three cases of tuberculous brain abscess in
      AIDS patients and review nine similar cases. The mean age was 30 years (range: 18
      56 years) with seven patients being male. Five (42%) were intravenous drug users,
      had prior history of extra-cerebral tuberculosis, and presented alterations on
      chest radiograph. Tuberculin skin test was anergic in six (75%) of eight
      patients. Three patients of nine had a CD4+ cell count higher than 200
      cells/microL, and three had a CD4+ cell count lower than 100 cells/microl. All
      but one patient had a brain computerized tomography scan with a single lesion.
      All patients received anti-tuberculous treatment and underwent surgical
      procedures. Most patients (75%) showed appropriate clinical responses.
      CONCLUSION: Tuberculous brain abscess must be considered in the differential
      diagnosis of intracranial mass in AIDS patients. A careful epidemiological,
      clinical and laboratory evaluation may guide a diagnostic suspicion. Surgery
      combined with specific anti-tuberculosis treatment seems to determine a good
      outcome.

PMID- 15964539
TI  - Brain abscess due to Mycobacterium tuberculosis in a patient with AIDS: report of
      a case and review of the literature.

PMID- 15964541
TI  - Direct methylation from mouse plasma and from liver and brain homogenates.
AB  - The analysis of fatty acid composition of plasma and tissue is important as a
      method for studying lipid nutrition. We investigated the possibility of direct
      methylation of fatty acids by BF(3)-methanol from plasma and from liver and brain
      homogenates without lipid extraction. There were no ghost peaks in the
      chromatogram produced by the direct methylation method. The 18:0 percentages were
      significantly higher in the direct methylation method than in the lipid
      extraction method. There were not remarkable differences in fatty acid
      composition in the direct methylation and methylation after lyophilization
      methods. Furthermore, the recovery ratio of the internal standard in the direct
      methylation method was higher than that in the lipid extraction method. The
      difference of fatty acid composition with lipid extraction may be caused by the
      change of lipid class extraction. Therefore, the direct methylation method
      without lipid extraction is the most suitable for determining fatty acid
      composition in plasma and tissue.

PMID- 15964542
TI  - Quantification of DNA strand breaks and abasic sites by oxime derivatization and
      accelerator mass spectrometry: application to gamma-radiation and peroxynitrite.
AB  - We report a highly sensitive method to quantify abasic sites and deoxyribose
      oxidation products arising in damaged DNA. The method exploits the reaction of
      aldehyde- and ketone-containing deoxyribose oxidation products and abasic sites
      with [(14)C]methoxyamine to form stable oxime derivatives, as originally
      described by Talpaert-Borle and Liuzzi [Reaction of apurinic/apyrimidinic sites
      with [(14)C]methoxyamine. A method for the quantitative assay of AP sites in DNA,
      Biochim. Biophys. Acta 740 (1983) 410-416]. The sensitivity of the method was
      dramatically improved by the application of accelerator mass spectrometry to
      quantify the (14)C, with a limit of detection of 1 lesion in 10(6) nucleotides in
      1 microg of DNA. The method was validated using DNA containing a defined quantity
      of abasic sites, with a >0.95 correlation between the quantities of abasic sites
      and those of methoxyamine labels. The original applications of this and similar
      oxyamine derivatization methods have assumed that abasic sites are the only
      aldehyde-containing DNA damage products. However, deoxyribose oxidation produces
      strand breaks and abasic sites containing a variety of degradation products with
      aldehyde and ketone moieties. To assess the utility of methoxyamine labeling for
      quantifying strand breaks and abasic sites, the method was applied to plasmid DNA
      treated with gamma-radiation and peroxynitrite. For gamma-radiation, there was a
      0.99 correlation between the quantity of methoxyamine labels and the quantity of
      strand breaks and abasic sites determined by a plasmid nicking assay; the abasic
      sites comprised less than 10% of the radiation-induced DNA damage. Studies with
      peroxynitrite demonstrate that the method, in conjunction with DNA repair enzymes
      that remove damaged bases to produce aldehydic sugar residues or abasic sites, is
      also applicable to quantifying nucleobase lesions in addition to strand break
      products. Compared to other abasic site quantification techniques, the modified
      method offers the advantage of providing a straightforward and direct measurement
      of aldehyde- and ketone-containing strand breaks and abasic sites, with the
      potential for direct labeling in cells prior to DNA isolation.

PMID- 15964543
TI  - ZNF383, a novel KRAB-containing zinc finger protein, suppresses MAPK signaling
      pathway.
AB  - Mitogen-activated protein kinases (MAPKs) are major components of pathways
      controlling embryogenesis, cell differentiation, cell proliferation, and cell
      death. One of the most explored functions of MAPK signaling is the regulation of
      gene expression by direct or indirect phosphorylation and subsequent activation
      of transcription factors. In this article, we isolated a novel KRAB-related zinc
      finger gene named ZNF383 from an early embryo heart cDNA library. The cDNA of
      ZNF383 is 2220bp, encoding a protein of 475 amino acids. The protein is conserved
      in evolution across different species. Northern blot analysis indicates that a
      2.2kb transcript specific for ZNF383 is detected in most of the examined human
      adult and embryonic tissues with a higher level in skeletal muscle. In COS-7
      cells, ZNF383 protein is localized to nucleus and cytoplasm. ZNF383 is a
      transcription repressor when fused to Gal-4 DNA-binding domain and cotransfected
      with VP-16. Deletion analysis indicates that the KRAB box of ZNF383 is
      responsible for the transcriptional repressor activity. Overexpression of ZNF383
      in cells inhibits the transcriptional activities of AP-1 and SRE, suggesting that
      ZNF383 may act as a negative regulator in MAPK-mediated signaling pathways.

PMID- 15964544
TI  - Al(3+) interaction sites of calmodulin and the Al(3+) effect on target binding of
      calmodulin.
AB  - The interaction between calmodulin (CaM) and Al(3+) was studied by spectroscopic
      methods. Heteronuclear two-dimensional NMR data indicated that peaks related to
      the both lobes and middle of the central helix of CaM are largely affected by
      Al(3+). But chemical shift perturbation suggested that overall conformation of
      Ca(2+)-loaded CaM is not changed by Al(3+) binding. It is thought that Al(3+)
      interaction to the middle of the central helix is a key for the property of CaM's
      target recognition. If the structure and/or flexibility of the central helix
      are/is changed by Al(3+), target affinity to CaM must be influenced by Al(3+).
      Thus, we performed surface plasmon resonance experiments to observe the effect of
      Al(3+) on the target recognition by CaM. The data clearly indicated that target
      affinity to CaM is reduced by addition of Al(3+). All the results presented here
      support a hypothesis that Al(3+) may affect on the Ca(2+) signaling pathway in
      cells.

PMID- 15964545
TI  - Characterization of the VP1 loop mutations widespread among JC polyomavirus
      isolates associated with progressive multifocal leukoencephalopathy.
AB  - Recently, we found that JC polyomavirus (JCPyV) associated with progressive
      multifocal leukoencephalopathy (PML) frequently undergoes amino acid
      substitutions (designated VP1 loop mutations) in the outer loops of the major
      capsid protein, VP1. To further characterize the mutations, we analyzed the VP1
      region of the JCPyV genome in brain-tissue or cerebrospinal fluid samples from 20
      PML patients. VP1 loop mutations occurred far more frequently than silent
      mutations. Polymorphic residues were essentially restricted to three positions
      (55, 60, and 66) within the BC loop, one (123) within the DE loop, and three
      (265, 267, and 269) within the HI loop. The mutations at most polymorphic
      residues showed a trend toward a change to specific amino acids. Finally, we
      presented evidence that the VP1 loop mutations were associated with the
      progression of PML. These findings should form the basis for elucidating the
      biological significance of the VP1 loop mutations.

PMID- 15964546
TI  - Expression of developmentally regulated endothelial cell locus 1 was induced by
      tumor-derived factors including VEGF.
AB  - Developmentally regulated endothelial cell locus 1 (Del1) is a new angiogenic
      molecules expressed specifically in early embryonic endothelial cells. We
      investigated the relationship between Del1 and tumor cell-derived vascular
      endothelial growth factor (VEGF). Dunn osteosarcoma cells and high- and low
      metastatic murine sarcoma cells did not express Del1. However, the expression of
      Del1 was observed in these primary tumor tissues and the pulmonary metastatic
      tissues after subcutaneous inoculation in vivo. Every tumor cell-conditioned
      medium containing VEGF induced the expression of Del1 in murine lung
      microvascular endothelial (MLE) cells, although control MLE cells did not express
      Del1. The anti-mouse VEGF monoclonal antibody inhibited the induction of the Del1
      expression. In addition, mouse recombinant interleukin-1alpha and tumor necrosis
      factor-alpha also induced Del1 in MLE cells. Del1 may play an important role in
      tumor angiogenesis through the effects of tumor-derived factors including VEGF.

PMID- 15964547
TI  - Cooperative activation of transcription by autoimmune regulator AIRE and CBP.
AB  - Autoimmune regulator (AIRE) is a transcriptional regulator that is believed to
      control the expression of tissue-specific genes in the thymus. Mutated AIRE is
      responsible for onset of the hereditary autoimmune disease APECED. AIRE is able
      to form nuclear bodies (NBs) and interacts with the ubiquitous transcriptional
      coactivator CBP. In this paper, we show that CBP and AIRE synergistically
      activate transcription on different promoter reporters whereas AIRE gene mutation
      R257X, found in APECED patients, interferes with this coactivation effect.
      Furthermore, the overexpression of AIRE and CBP collaboratively enhance
      endogenous IFNbeta mRNA expression. The immunohistochemical studies suggest that
      CBP, depending on the balance of nuclear proteins, is a component of AIRE NBs. We
      also show that AIRE NBs are devoid of active chromatin and, therefore, not sites
      of transcription. In addition, we demonstrate by 3D analyses that AIRE and CBP,
      when colocalizing, are located spatially differently within AIRE NBs. In
      conclusion, our data suggest that AIRE activates transcription of the target
      genes, i.e., autoantigens in collaboration with CBP and that this activation
      occurs outside of AIRE NBs.

PMID- 15964548
TI  - Characterization of the PR domain of RIZ1 histone methyltransferase.
AB  - RIZ1 (PRDM2) and PRDI-BF1 (PRDM1) are involved in B cell differentiation and the
      development of B cell lymphomas. These proteins are expressed in two forms that
      differ by the presence or absence of a PR domain. The protein product that
      retains the PR domain is anti-tumorigenic while the product that lacks the PR
      domain is oncogenic and over-expressed in tumor cells. The conserved PR domain is
      homologous to the SET domain from a family of histone methyltransferases. RIZ1 is
      also a histone methyltransferase and methylates lysine 9 in histone H3. This
      activity has been mapped to the PR domain. In the present study, deuterium
      exchange mass spectrometry was used to define the structural boundaries of the
      RIZ1 PR domain and to map sites of missense mutations that occur in human cancers
      and reduce methyltransferase activity. Flexible segments were selectively deleted
      to produce protein products that crystallize for structural studies. Segments at
      the carboxyl terminus of the PR domain that are involved in methylation of H3
      were shown to be flexible, similar to SET domains, suggesting that the PR and SET
      methyltransferases may belong to an emerging class of proteins that contain
      mobile functional regions.

PMID- 15964549
TI  - Heterogeneous nuclear ribonucleoprotein B1 protein impairs DNA repair mediated
      through the inhibition of DNA-dependent protein kinase activity.
AB  - Heterogeneous nuclear ribonucleoprotein B1, an RNA binding protein, is
      overexpressed from the early stage of lung cancers; it is evident even in
      bronchial dysplasia, a premalignant lesion. We evaluated the proteins bound with
      hnRNP B1 and found that hnRNP B1 interacted with DNA-dependent protein kinase
      (DNA-PK) complex, and recombinant hnRNP B1 protein dose-dependently inhibited DNA
      PK activity in vitro. To test the effect of hnRNP B1 on DNA repair, we performed
      comet assay after irradiation, using normal human bronchial epithelial (HBE)
      cells treated with siRNA for hnRNP A2/B1: reduction of hnRNP B1 treated with
      siRNA for hnRNP A2/B1 induced faster DNA repair in normal HBE cells. Considering
      these results, we assume that overexpression of hnRNP B1 occurring in the early
      stage of carcinogenesis inhibits DNA-PK activity, resulting in subsequent
      accumulation of erroneous rejoining of DNA double-strand breaks, causing tumor
      progression.

PMID- 15964550
TI  - One in vitro model for visceral adipose-derived fibroblasts in chronic
      inflammation.
AB  - One pathogenesis of the obesity-associated complications is that consistent with
      increased body fat mass, the elevation of adipose tissue-derived cytokines
      inflicts a low-grade chronic inflammation, which ultimately leads to metabolic
      disorders. Adipocytes and macrophages in visceral adipose (VA) have been
      confirmed to contribute to the chronic inflammation; however, the role of the
      resident fibroblasts is still unknown. We established one VA fibroblast cell
      line, termed VAFC. Morphological analysis indicated that there were large numbers
      of pits at the cell plasma membrane. In vitro VAFC cells promoted bone marrow
      cells to differentiate into macrophages and protected them from apoptosis in the
      serum-free conditions. Additionally, they also interfered in lymphocytes
      proliferation. On the basis of these results, this cell line might be an in vitro
      model for understanding the role of adipose-derived fibroblasts in obesity
      associated chronic inflammation.

PMID- 15964551
TI  - The non-selective cation-permeable channel TRPC3 is a tetrahedron with a cap on
      the large cytoplasmic end.
AB  - TRPC3 plays important roles in neuronal differentiation and immune cell
      maturation by mediating the cationic current in response to phospholipase C
      activation, Ca2+ depletion, and diacylglycerol stimulation. Here, we purified the
      TRPC3 channel using a glycosylated tetramer and observed the structure using
      electron microscopy. Negatively stained specimens demonstrate homogeneous protein
      particles containing an internal cavity-like structure. These particle images
      were picked up by automated pick-up programs, aligned, and classified by the
      growing neural gas network method. Similarly oriented projections were averaged
      to decrease the signal-to-noise ratio. The averaged images progress from the top
      view to the side views, which are representative of their raw images. The top
      view confirmed the hypothesis of a four-domain structure, and the side view
      demonstrates a large cytoplasmic domain with a capped structure at the bottom,
      which is near a predicted locus of ion release. The total image of the protein is
      a blunt-edged trapezoid of 200 x 200 x 235 A. This large dimension of TRPC3 is
      also supported by the Stokes radius (92 A) obtained from gel filtration
      chromatography.

PMID- 15964552
TI  - Photodynamic effects of a novel pterin derivative on a pancreatic cancer cell
      line.
AB  - 6-Formylpterin (6FP) has the potential to produce singlet oxygen (1O2) under UV-A
      radiation. In order to apply this potential to anti-cancer photodynamic therapy
      (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6
      formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic
      effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser
      scanning confocal microscopy showed that the drug uptake, the 1O2 generation, and
      cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena
      were not observed in the 6FP-treated cells. The MTT assay also showed the
      decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and
      6FP-tBu-DMF generate 1O2 to the same extent under UV-A radiation in aqueous
      solutions, these results indicated that the differences in the photodynamic
      effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences
      in the cell permeability between them. The development of cell permeable pterin
      derivatives has the potential for application in PDT.

PMID- 15964553
TI  - TSSK5, a novel member of the testis-specific serine/threonine kinase family,
      phosphorylates CREB at Ser-133, and stimulates the CRE/CREB responsive pathway.
AB  - Several protein kinases have been shown to be involved in spermatogenesis.
      Recently, a novel subfamily of serine/threonine kinases has been isolated whose
      expression is limited to testis. Here, we report the fifth family member, named
      TSSK5, which encodes a 328 amino acid protein. RT-PCR analysis showed that TSSK5
      is exclusively expressed in human testis. We isolated cAMP responsive element
      binding protein (CREB), a TSSK5 interacting protein via yeast two-hybrid system.
      The in vitro kinase assay showed that TSSK5 phosphorylated CREB at Ser-133. Using
      a CRE reporter system, we found that TSSK5 could stimulate the CREB/CRE
      responsive pathway in Hek293 cells. These results suggest that this kinase may be
      involved in spermatogenesis through phosphorylating CREB and then stimulating the
      CREB/CRE responsive pathway.

PMID- 15964554
TI  - ZNF328, a novel human zinc-finger protein, suppresses transcriptional activities
      of SRE and AP-1.
AB  - The zinc finger proteins containing the Kruppel-associated box domain (KRAB-ZFPs)
      are the single largest class of transcription factors in human genome. Many of
      the KRAB-ZFPs are involved in cardiac development or cardiovascular diseases.
      Here, we have identified a novel human KRAB zinc finger gene, named ZNF328, from
      the human fetal heart cDNA library. The complete sequence of ZNF328 cDNA contains
      a 2376-bp open reading frame (ORF) and encodes a 792 amino acid protein with an N
      terminal KRAB domain and classical zinc finger C2H2 motifs in the C-terminus.
      Northern blot analysis indicates that the protein is expressed in most of the
      examined human adult and embryonic tissues. ZNF328 is a transcription suppressor
      when fused to Gal-4 DNA-binding domain and cotransfected with VP-16.
      Overexpression of ZNF328 in COS-7 cells inhibits the transcriptional activities
      of SRE and AP-1. Deletion analysis with a series of truncated fusion proteins
      indicates that the KRAB motif is a basal repression domain when cotransfected
      with VP-16. Similar results were obtained when the truncated fusion proteins were
      assayed for the transcriptional activities of SRE and AP-1. These results suggest
      that ZNF328 protein may act as a transcriptional repressor in mitogen-activated
      protein kinase (MAPK) signaling pathway to mediate cellular functions.

PMID- 15964555
TI  - Protein interactions within the TcZFP zinc finger family members of Trypanosoma
      cruzi: implications for their functions.
AB  - The small zinc finger proteins tbZFP1 and tbZFP2 have been implicated in the
      control of Trypanosoma brucei differentiation to the procyclic form. Here, we
      report that the complete ZFP family in Trypanosoma cruzi is composed by four
      members, ZFP1A and B, and ZFP2A and B. ZFP1B is a paralog specific gene
      restricted to T. cruzi, while the ZFP2A and B paralogs diverged prior to the
      trypanosomatid lineage separation. Moreover, we demonstrate that TcZFP1 and
      TcZFP2 members interact with each other and that this interaction is mediated by
      a WW domain in TcZFP2. Also, TcZFP2B strongly homodimerizes by a glycine rich
      region absent in TcZFP2A. We propose a model to discuss the relevance of these
      protein-protein interactions in terms of the functions of these proteins.

PMID- 15964556
TI  - Matrix metalloproteinase-7 degrades all insulin-like growth factor binding
      proteins and facilitates insulin-like growth factor bioavailability.
AB  - Proteolytic modification of insulin-like growth factor binding proteins (IGFBPs)
      plays an important physiological role in regulating insulin-like growth factor
      (IGF) bioavailability. Recently, we demonstrated that matrix metalloproteinase-7
      (MMP-7)/Matrilysin produced by various cancer cells catalyzes the proteolysis of
      IGFBP-3 in vitro and regulates IGF bioavailability, resulting in an anti
      apoptotic effect against anchorage-independent culture. In the present study, we
      investigated whether MMP-7 contributes to proteolysis of the other five IGFBPs,
      IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6, and whether this results in
      phosphorylation of the IGF type 1 receptor (IGF-1R). MMP-7 cleaved all six
      IGFBPs, resulting in IGF-mediated IGF-1R phosphorylation, which was inhibited by
      EDTA treatment. These results suggest that MMP-7 derived from cancer cells can
      regulate IGF bioavailability in the microenvironment surrounding the tumor, where
      various kinds of IGF/IGFBP complexes are found, thereby favoring cancer cell
      growth and survival during the processes of invasion and metastasis.

PMID- 15964557
TI  - TCR pathway involves ICBP90 gene down-regulation via E2F binding sites.
AB  - Antigen-induced cell death is essential for function, growth and differentiation
      of T-lymphocytes through legation of the T cell receptor. Since TCR-induced cell
      death occurs at late G1 checkpoint of the cell cycle and considering that ICBP90
      is critical for G1/S transition, we studied the ICBP90 regulation through the TCR
      pathway in Jurkat cells. ICBP90 expression was strongly decreased after TCR
      triggering concomitantly to cyclin D3 and topoisomerase IIalpha expression
      decreases. Cell stimulation with PMA and/or calcium ionophore A23187 down
      regulated ICBP90 expression. The decrease of ICBP90 protein and mRNA expressions
      was accompanied with cell growth arrest. A luciferase reporter assay demonstrated
      that activation of TCR pathways inhibit ICBP90 gene promoter activity. Three
      consensus E2F binding sites (called from E2F-a to E2F-c) were identified in the
      ICBP90 gene promoter and were subjected to mutations. The E2F-a, located in a
      highly active promoter fragment, shows a strong positive functional activity in
      proliferating cells. E2F-a and E2F-c binding sites are involved in the TCR
      induced down-regulation of ICBP90 gene transcription. Altogether, our data
      demonstrate that TCR signaling pathways regulate ICBP90 gene expression through
      pRb/E2F complex. We propose that ICBP90 down-regulation is a key event in G1
      arrest preceding T cell death.

PMID- 15964558
TI  - Partial cell fusion: a newly recognized type of communication between
      dedifferentiating cardiomyocytes and fibroblasts.
AB  - OBJECTIVE: Fibroblasts have been shown to couple to neonatal cardiomyocytes in
      heterocellular cultures through functional gap junctions. Our objective was to
      provide evidence for an additional type of heterocellular communication between
      fibroblasts and adult cardiomyocytes in vitro and in vivo. METHODS: The contact
      areas in heterocellular co-cultures were evaluated by specific labeling and the
      intercellular communication was studied using preloading of fibroblasts with
      tracer molecules. Heterocellular fibroblast-cardiomyocyte contacts present in the
      in vitro setting and in the border zone of a rabbit myocardial infarction in vivo
      were further examined by electron microscopy. RESULTS: Addition of fibroblasts
      preloaded with the fluorescent low molecular weight tracer calcein-AM to cultured
      myocytes indicated early dye transfer via connexin 43 functional gap junctions.
      At a later time-period after co-culturing, dye transfer of fibroblasts preloaded
      with the high molecular weight tracer dextran 10,000 suggested partial cell
      fusion. The membrane continuity giving rise to this partial cell fusion was
      confirmed by electron microscopy, clearly showing areas of intercytoplasmic
      contacts between fibroblasts and phenotypically adapted (dedifferentiated)
      cardiomyocytes. Fluorescein-labeled annexin V affinity studies revealed transient
      exposure of phosphatidylserine at the contact sites, suggesting that
      phosphatidylserine mediates the fusion process. Close contacts between cardiac
      fibroblasts and dedifferentiated cardiomyocytes accompanied by disruption of the
      basal lamina were observed in the border zone of a rabbit myocardial infarction
      in vivo. CONCLUSION: Our results suggest that the partial cell fusion-type of
      heterocellular communication in our co-culture model and the contacts observed in
      vivo may lead to new insights in cardiovascular disease.

PMID- 15964559
TI  - Expression of insulin-like growth factor-1 and insulin-like growth factor-1
      receptors in EL4 lymphoma cells overexpressing growth hormone.
AB  - Almost all of the previous studies with growth hormone (GH) have been done with
      exogenously supplied GH and, therefore, involve actions of the hormone through
      its receptor. However, the actions of endogenous or lymphocyte GH are still
      unclear. In a previous study, we showed that overexpression of GH (GHo) in a
      lymphoid cell line resulted in protection of the cells to apoptosis mediated by
      nitric oxide (NO). In the present study, we show that the protection from
      apoptosis could be transferred to control cells with culture fluids obtained from
      GHo cells and blocked by antibodies to the insulin-like growth factor-1 (IGF-1)
      or antibodies to the IGF-1-receptor (IGF-1R). Northern and Western blot analysis
      detected significantly higher levels of IGF-1 in cells overexpressing GH. An
      increase in the expression of the IGF-1R in GHo cells was also detected by
      Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter
      luciferase constructs. Transfection of GHo cells with a dominant negative IGF-1R
      mutant construct blocked the generation of NO and activation of Akt seen in GHo
      cells compared to vector alone control EL4 cells. The results suggest that one of
      the consequences of the overexpression of GH, in cells lacking the GH receptor,
      is an increase in the expression of IGF-1 and the IGF-1R which mediate the
      protection of EL4 lymphoma cells from apoptosis.

PMID- 15964560
TI  - Protective effect of lipoic acid on adriamycin-induced testicular toxicity.
AB  - BACKGROUND: Adriamycin (ADR), an anthracycline antibiotic, which is widely used
      as an antineoplastic drug in the treatment of various solid tumors, has been
      shown to induce reproductive abnormalities in males. In the present study, the
      effect of lipoic acid (LA), a universal antioxidant, was investigated on ADR
      induced testicular toxicity in rats. METHODS: Adult male albino rats of Wistar
      strain were administered ADR (1 mg/kg body weight, i.v.), once a week for 10
      weeks. Semen quality was evaluated in terms of sperm count, percentage motility
      and abnormality. The testicular damage was also assessed by the measurement of
      marker enzymes activities and histology. RESULTS: ADR treated rats showed a
      significant decrease in sperm count and motility while an increase in dead and
      abnormal sperms. The activities of testicular marker enzymes such as gamma
      glutamyl transferase, beta-glucuronidase, acid phosphatase and alkaline
      phosphatase were increased whereas the activity of lactate dehydrogenase-X was
      decreased significantly in the animals treated with ADR. ADR treated rats also
      showed abnormal histologic findings. Treatment with lipoic acid (35 mg/kg body
      weight, i.p.) 1 day prior to ADR administration, improved the semen quality and
      maintained near normal activities of the enzymes. CONCLUSION: By the reversal of
      biochemical and morphological changes towards normalcy, the cytoprotective role
      of LA is illuminated in ADR-induced testicular toxicity.

PMID- 15964561
TI  - Economic consequence of immediate testing for C-reactive protein and leukocyte
      count in new outpatients with acute infection.
AB  - BACKGROUND: There have been few well-designed studies that assess the cost
      effectiveness of near-patient immediate testing. METHODS: We analyzed the
      economic outcome of immediate testing for C-reactive protein (CRP) and white
      blood cell count (WBC) in 305 new outpatients with acute infections. Patients
      were randomized into two groups: 147 patients were tested immediately for CRP and
      WBC before the physician's initial consultation (advance testing), and 154
      patients were not subjected to advance testing. The subsequent prescribing
      decision and the drug/testing/personnel costs were compared between the groups.
      RESULTS: In the advance-testing group, the initial consultation was followed by a
      total of 84 prescriptions of oral antibiotics, against 158 in the other group.
      Comparing the total costs of oral and parenteral antibiotics between the two
      groups, a 30% reduction was achieved with advance testing ( yen105,830 vs.
      yen151,102). However, the savings were largely offset by frequent prescription of
      newer, expensive influenza neuraminidase inhibitors. Advance testing also
      significantly reduced additional laboratory use. More frequent urgent testing
      increased personnel costs in the non-advance-testing group. Overall, total cost
      was somewhat higher in the advance-testing group ( yen1,028,827 vs. yen984,105).
      CONCLUSIONS: The cost per antibiotic prescription reduced with advance testing
      was yen604 (approximately 5.8 US dollars) in our clinical setting. Judicious use
      of antivirals and introduction of a simple CRP test kit would improve cost
      effectiveness.

PMID- 15964562
TI  - Developmental decisions in Dictyostelium discoideum.
AB  - Dictyostelium discoideum is an excellent system in which to study developmental
      decisions. Synchronous development is triggered by starvation and rapidly
      generates a limited number of cell types. Genetic and image analyses have
      revealed the elegant intricacies associated with this simple development system.
      Key signaling pathways identified as regulating cell fate decisions are likely to
      be conserved with metazoa and are providing insight into differentiation
      decisions under circumstances where considerable cell movement takes place during
      development.

PMID- 15964563
TI  - Nomega-hydroxy-L-arginine homologues and hydroxylamine as nitric oxide-dependent
      vasorelaxant agents.
AB  - Endothelium-independent relaxant activities of N(omega)-hydroxy-L-arginine (L
      NOHA) homologues and hydroxylamine, a possible intermediate in nitric oxide (NO)
      formation, were examined in rat aortic rings. Addition of one -CH(2)- group to
      the -(CH(2))(x)- chain between the alpha-amino acid and the hydroxyguanidine
      group (x=4) almost abolished-while deletion of one or two -CH(2)- (x=1 or 2)
      enhanced-the relaxant activity of L-NOHA homologues. N(omega)-hydroxy-nor-L
      arginine- (x=2) and hydroxylamine-induced relaxations were blunted by a NO
      scavenger and by inhibitors of the guanylyl cyclase pathway, but not by NO
      synthase or cytochrome P(450) inhibitors (except 7-ethoxyresorufin). However,
      aortic NO formation was detected (using electron paramagnetic resonance) in the
      presence of concentrations of these compounds higher than those producing
      relaxation. These findings support the view that endothelium-independent
      vasorelaxations induced by both L-NOHA homologues with a required chain length
      x</=3 and hydroxylamine are mediated by NO-dependent activation of guanylyl
      cyclase, through a 7-ethoxyresorufin-inhibited mechanism.

PMID- 15964565
TI  - The role of endothelin in FK506-induced vascular reactivity changes in rat
      perfused kidney.
AB  - Tacrolimus (FK506) is an immunosuppressant agent that is widely used in
      transplanted patients. The aim of this study was to investigate the role of
      endothelin in the acute effects of FK506 on the vascular reactivity in perfused
      isolated rat renal and mesenteric vasculature. Left kidney/mesentery of male
      Wistar rats (230-300 g) were perfused by a constant flow and perfusion pressure
      was recorded. The responses to noradrenaline and sodium nitroprusside were
      obtained both in the absence and presence of FK506 (10(-7) M) or polyoxyethylene
      hydrogenated castor oil 60 (HCO-60 and solvent of the drug at equivalent
      concentrations). FK506 significantly increased the noradrenaline-induced
      vasoconstrictor responses in renal, but not in mesenteric vascular beds. Bosentan
      (10(-5) M), a nonselective endothelin ET-1 receptor antagonist given by
      perfusion, reversed the increase in noradrenaline responses in the kidney. Sodium
      nitroprusside-induced vasodilator responses in both renal and mesenteric vascular
      beds were significantly decreased by FK506. However, in renal vasculature, there
      was no significant difference between the inhibitory effects of FK506 and HCO-60,
      although the effect of the solvent was not significantly different from that of
      the control. While in the mesenteric bed, the solvent significantly inhibited
      nitroprusside-induced vasodilation, similar to that of FK506. The effect of FK506
      on vasodilation in both vascular beds was not reversed by bosentan. Our results
      indicated that FK506 increased the reactivity of the renal vascular bed to
      noradrenaline through endothelin ET-1 receptor activation. The mechanism of
      impaired vasodilation due to FK506 appears to be due to its solvent action and is
      independent of endothelin release.

PMID- 15964564
TI  - Modulation of neutrophil and inflammation markers in chronic obstructive
      pulmonary disease by short-term azithromycin treatment.
AB  - The anti-inflammatory potential of azithromycin in chronic obstructive pulmonary
      disease (COPD) patients was explored following a standard oral dosing regimen.
      Patients with moderate and severe COPD were treated with azithromycin (500 mg,
      n=16) or placebo (n=8) once daily for 3 days in a randomized, double blind
      design, to compare effects on inflammation markers with those seen in a previous
      study in healthy volunteers. A battery of tests was made on serum, blood
      neutrophils and sputum on days 1 (baseline), 3, 4, 11, 18 and 32. In comparison
      to placebo, azithromycin resulted in an early transient increase in serum
      nitrites plus nitrates (day 3), associated with a tendency towards an increase in
      the blood neutrophil oxidative burst to phorbol myristic acetate. Subsequently,
      prolonged decreases in blood leukocyte and platelet counts, serum acute phase
      protein (including C reactive protein) and soluble E-selectin and blood
      neutrophil lactoferrin concentrations and a transient decrease in serum
      interleukin-8 were observed. Blood neutrophil glutathione peroxidase activity
      showed a prolonged increase after azithromycin treatment. The biphasic
      facilitatory-then-inhibitory response to azithromycin seen in healthy volunteers
      is not so clearly detectable in COPD patients, only potential anti-inflammatory
      effects. Treatment for longer periods may give therapeutic anti-inflammatory
      benefit in these patients.

PMID- 15964566
TI  - Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and
      muscarinic M(3) receptor-dependent.
AB  - Emerging evidence indicates that some secondary bile acids interact functionally
      with muscarinic cholinergic receptors. Using thoracic aortic rings prepared from
      rats and mice, we examined the mechanism of deoxycholyltaurine-induced
      vasorelaxation. Increasing concentrations of both acetylcholine (1 nM to 0.1 mM)
      and deoxycholyltaurine (0.1 microM to 1 mM) stimulated relaxation of
      phenylephrine-constricted rings prepared from rat thoracic aortae. These effects
      were reduced by endothelial denudation and by treatment with an inhibitor of
      nitric oxide formation and with a synthetic acetylcholine:bile acid hybrid that
      acts as a muscarinic receptor antagonist. Likewise, both acetylcholine (1 nM to
      0.1 mM) and deoxycholyltaurine (0.1 microM to 0.1 mM) stimulated relaxation of
      phenylephrine-constricted rings prepared from mouse thoracic aortae. These
      effects were reduced by endothelial denudation, addition of an inhibitor of
      nitric oxide formation, and by muscarinic M(3) receptor knockout. We conclude
      that the systemic vasodilatory actions of deoxycholyltaurine are mediated in part
      by a nitric oxide-, muscarinic M(3) receptor-dependent mechanism. In advanced
      liver disease, interaction of serum bile acids with endothelial muscarinic
      receptors may explain nitric oxide overproduction in the systemic circulation and
      resulting peripheral arterial vasodilation.

PMID- 15964567
TI  - The dual role of prostaglandin E(2) in excitotoxicity and preconditioning-induced
      neuroprotection.
AB  - Cyclooxygenase-2 is harmful in models of cerebral ischemia yet plays a protective
      role in preconditioning-induced ischemic tolerance in the heart. This study
      examined the mechanisms underlying cyclooxygenase-2-mediated neurotoxicity and
      preconditioning-induced neuroprotection in an in vitro model of cerebral
      ischemia. Inhibition of cyclooxygenase-2 protects cortical neuronal cultures from
      death induced by oxygen-glucose deprivation and reduces oxygen-glucose
      deprivation-induced increases in intracellular Ca(2+) ([Ca(2+)](i)). In the
      present study, we determined if prostaglandin E(2) (PGE(2)) is responsible for
      this cyclooxygenase-2-mediated effect. Rat cortical cultures expressed mRNA for
      the prostanoid EP(1)-EP(4) receptors. PGE(2) reversed the attenuation in
      [Ca(2+)](i) and the protection offered by cyclooxygenase-2 inhibition during
      oxygen-glucose deprivation. These effects likely occur via activation of the
      prostanoid EP(1) receptor since blocking this receptor during oxygen-glucose
      deprivation reduced [Ca(2+)](i) and neurotoxicity. Next, we considered if the
      moderate activation of this pathway, by preconditioning cultures with sub-lethal
      oxygen-glucose deprivation, influenced the development of tolerance to an
      otherwise lethal oxygen-glucose deprivation insult, 48 h later. Inhibition of
      cyclooxygenase-2 during oxygen-glucose deprivation-preconditioning abolished
      preconditioning-induced protection. Furthermore, cultures were rendered tolerant
      to oxygen-glucose deprivation by the transient exposure to exogenous PGE(2) 24 h
      prior to the insult, indicating that this product of the cyclooxygenase-2 pathway
      is sufficient to induce ischemic tolerance. This study shows that cyclooxygenase
      2 and PGE(2) are involved in both oxygen-glucose deprivation-induced
      neurotoxicity and preconditioning-induced neuroprotection. While neurotoxic in
      the context of lethal oxygen-glucose deprivation, the moderate activation of this
      signalling pathway confers ischemic tolerance.

PMID- 15964568
TI  - Comparison of early passage, senescent and hTERT immortalized endothelial cells.
AB  - The need for standardized experimental conditions to gain relevant and
      reproducible results has increased the demand for well characterized continuously
      growing cell lines that exhibit the characteristics of their normal counterparts.
      Immortalization of normal human cells by ectopic expression of the catalytic
      subunit of human telomerase (hTERT) has shown to result in highly differentiated
      cell lines. However, the influence of the increased telomerase activity on the
      protein expression profile was not investigated so far. Therefore, we have
      immortalized human umbilical vein endothelial cells (HUVECs) by hTERT
      overexpression and compared them to their normal early passage and senescent
      counterparts. This study, including a proteomic approach, shows that ectopic
      hTERT expression leads to a stable growing cell line. Although these cells are
      highly differentiated, the protein expression profile of the cell line is
      different to that of normal early passage and senescent cells.

PMID- 15964569
TI  - Charge substitution shows that repulsive electrostatic interactions impede the
      oligomerization of Alzheimer amyloid peptides.
AB  - The strong pH dependence of A beta oligomerization could arise from favorable
      intermolecular charge-charge interactions between His and carboxylate groups, or,
      alternatively, by mutual electrostatic repulsion of peptide molecules. To test
      between these two possibilities, the pH dependence of the oligomerization of A
      beta and three charge substitution variants with Asp, Glu and His substituted by
      Ala is measured. All four peptides oligomerize, as detected by thioflavin T
      fluorescence, turbidity, and amyloid fibril formation; therefore, specific charge
      charge interactions are nonessential for oligomerization. The strong negative
      correlation between net charge and oligomerization indicates that electrostatic
      repulsion between A beta monomers impedes their association.

PMID- 15964570
TI  - The floating shoulder.
AB  - Ipsilateral scapular neck and clavicular shaft fractures comprise the so-called
      "floating shoulder". This rare injury, which is, in general, caused by a high
      energy trauma, is perceived to be an unstable injury with the considerable risk
      of significant displacement of scapular neck and/or the clavicular fracture. An
      understanding of the patho-anatomy is important in identifying a floating
      shoulder and to offer rational treatment for this injury. The current status of
      the anatomical, biomechanical and clinical aspects of a floating shoulder is
      reviewed in this article. Recommendations for treatment of particularly displaced
      ipsilateral fractures of the scapular neck and clavicular shaft cannot be derived
      from the reported clinical studies. The possible correlation between functional
      outcome and malunion of the scapular neck is called into doubt.

PMID- 15964571
TI  - Comparing logistic models based on modified GCS motor component with other
      prognostic tools in prediction of mortality: results of study in 7226 trauma
      patients.
AB  - A simple reproducible and sensitive prognostic trauma tool is still needed. In
      this article we have introduced modified GCS motor response (MGMR) and evaluated
      the performance of logistic models based on this variable. The records of 8452
      trauma patients admitted to major hospitals of Tehran from 1999 to 2000 were
      analysed. 7226 records with known outcome were included in our study. Logistic
      models based on outcome (death versus survival) as a dependent variable and
      Injury Severity Score (ISS), Revised Trauma Score (RTS), Glasgow Coma Scale
      (GCS), GCS motor component (GMR) and MGMR (following command [=2], movement but
      not following [=1] command and without movement [=0]) were compared based on
      their accuracy and area under the Receiver Operating Characteristic (ROC) curve.
      The accuracy of the Trauma and Injury Severity Score (TRISS), RTS, GCS, GMR and
      MGMR models were almost the same. Considering both the area under the ROC curve
      and accuracy, the age included MGMR model was also comparable with other age
      included models (RTS+age, GCS+age, GMR+age). We concluded that although in some
      situations we need more sophisticated models, should our results be reproducible
      in other populations, MGMR (with or without age added) model may be of
      considerable practical value.

PMID- 15964572
TI  - Risk factors for emergency peripartum cesarean hysterectomy.

PMID- 15964573
TI  - Antigens of selected Acanthamoeba species detected with monoclonal antibodies.
AB  - Acanthamoeba species are ubiquitous soil and freshwater protozoa that have been
      associated with infections of the human brain, skin, lungs and eyes. Our aim was
      to develop specific antibodies to aid in rapid and specific diagnosis of
      clinically important isolates. Mice were variously immunised with live mixtures
      of Acanthamoeba castellanii strain 112 (AC112) trophozoites and cysts, or with
      sonicated, formalin-fixed or heat-treated trophozoites, or with a trophozoite
      membrane preparation. Eight hybridoma cell lines secreting monoclonal antibodies
      reactive with A. castellanii epitopes were generated. Seven of the new antibodies
      (designated AMEC1-3 and MTAC1-4) were isotyped as IgMkappa and one (MTAC5) as
      IgG1kappa. All of the novel antibodies bound to AC112 cysts, and MTAC4 and MTAC5
      also bound to trophozoites as measured by flow cytometry on unfixed cells. Single
      chain antibody fragments that retained parental antibody binding characteristics
      were engineered from three of the hybridomas (AMEC1, MTAC3 and MTAC4). Four
      monoclonal antibodies (AMEC1, AMEC3, MTAC1, MTAC3) bound reliably to unfixed
      cysts of clinical isolates of A. castellanii (two strains) and Acanthamoeba
      polyphaga (two strains), belonging to Pussard-Pons morphological group II, and to
      Acanthamoeba lenticulata and Acanthamoeba culbertsoni, belonging to Pussard-Pons
      morphological group III. None of the antibodies bound to cysts or trophozoites of
      the environmental group I species, Acanthamoeba tubiashi. Antibodies AMEC1,
      MTAC3, MTAC4 and MTAC5 reacted with buffered formalin-fixed AC112 by
      immunohistochemistry, and also stained Acanthamoeba in sections of infected rat
      cornea and buffered formalin-fixed, paraffin-embedded infected human cornea.
      These antibodies may be useful in diagnosing pathogenic Acanthamoeba species in
      clinical specimens, provided that cysts are present.

PMID- 15964574
TI  - Toxicity of Bacillus thuringiensis to parasitic and free-living life-stages of
      nematode parasites of livestock.
AB  - A collection of Bacillus thuringiensis (Bt) strains (Bts) were screened for
      activity against the free-living larval stages of nematode parasites of
      livestock. Two strains were identified with significant activity in inhibiting
      larval development of Haemonchus contortus, Trichostrongylus colubriformis and
      Ostertagia circumcincta. These strains were also toxic to the adult parasitic
      stages of these nematode species in vitro. Adult H. contortus and O. circumcincta
      showed complete cessation of movement within 2 and 4 days, respectively.
      Trichostrongylus colubriformis adults were less affected, however, movement was
      still significantly reduced compared with controls. The in vitro activity against
      the larval stages was of a magnitude similar to or greater than that seen with
      the anthelmintic drugs thiabendazole and levamisole. N-terminal amino acid
      sequencing indicated that the two Bts contained either Cry5A and Cry5B proteins,
      or a Cry13 protein, and the presence of the corresponding cry5A, cry5B and cry13
      genes was confirmed by PCR and sequencing. Bacillus thuringiensis spore-crystal
      suspensions exposed to acidic pH conditions (pH<or=3) showed greatly reduced
      toxicity in subsequent bioassays with nematode larvae, highlighting the need to
      protect the toxin from the acidic conditions of the sheep abomasum if it were to
      be administered per os as an anthelmintic. This study indicates that both the
      parasitic adult stages and the free-living larval stages of economically
      significant nematode parasites are susceptible to the effects of Bt, thus
      identifying this group of toxins as potential biocontrol agents.

PMID- 15964575
TI  - Trichinella britovi etiological agent of sylvatic trichinellosis in the Republic
      of Guinea (West Africa) and a re-evaluation of geographical distribution for
      encapsulated species in Africa.
AB  - In West Africa, Trichinella infection was documented in humans and animals from
      Senegal in the 1960s, and the biological characters of one isolate showed a lower
      infectivity to domestic pigs and rodents when compared with that of a Trichinella
      spiralis pig isolate from Europe. To identify the Trichinella species present in
      West Africa, a survey was conducted in a total of 160 wild animals in the
      Republic of Guinea. Three Viverridae, one true civet (Viverra civetta) and two
      African palm civets (Nandinia binotata) from the Fouta Djallon Massif, Pilimini
      Subprefecture, were found positive by artificial digestion of muscle samples.
      Trichinella larvae from these three viverrids were identified as Trichinella
      britovi and no difference was detected in three examined sequences from these
      African isolates and the reference strain of T. britovi from Europe, indicating
      common ancestry, an historically continuous geographic distribution, and recent
      isolation for African and European populations. The detection of T. britovi in
      West Africa modifies our knowledge about the distribution of encapsulated species
      of Trichinella in Africa. Thus, Trichinella nelsoni is now considered to have a
      distribution limited to the Eastern part of the Afrotropical region from Kenya to
      South Africa. This provides a plausible explanation for the presence of
      Trichinella T8 in Namibia and South Africa, and further suggests that T. britovi
      could be the Trichinella species circulating among wild animals of Northern
      Africa.

PMID- 15964576
TI  - Brownian dynamics simulation and experimental study of colloidal particle
      deposition in a microchannel flow.
AB  - This paper reports an analysis of the irreversible deposition of colloidal
      particles from the pressure-driven flow in a microchannel within the framework of
      DLVO theory. A theoretical model is presented on the basis of the stochastic
      Langevin equation, incorporating the random Brownian motion of colloidal
      particles. Brownian dynamics simulation is used to compute the particle
      deposition in terms of the surface coverage. To validate the theoretical model,
      experiments are carried out using the parallel-plate flow cell technique,
      enabling direct videomicroscopic observation of the deposition kinetics of
      polystyrene latex particles in NaCl electrolytes. The theoretical predictions are
      compared with the experimental results, and good agreement is found.

PMID- 15964578
TI  - Comparison of the characteristic behavior of two azo dyes on temperature
      dependent microstructure changes in micelles and vesicles.
AB  - The new hydrophobic azo dye 4-(N-phenyl-N-decylamino)-4'-nitroazobenzene (AzoC10)
      has been synthesized. It is compared with 4-(N-phenylamino)-4'-nitroazobenzene
      (Azo) in terms of reactivity (k(iso) of the thermal cis-->trans isomerization,
      microsecond flash photolysis) and of the solvatochromic behavior (lambda(max) of
      the trans-isomer, UV/vis absorption), respectively, within membrane mimeting
      amphiphile microstructures in aqueous solutions of poly(ethylene oxide)(m)
      poly(propylene oxide)(n)-poly(ethylene oxide)(m) micelles and of extruded
      vesicles. The temperature-induced micelle formation and phase transitions in
      bilayers of vesicles, respectively, caused characteristic discontinuous changes
      of k(iso) and lambda(max) with temperature. They differ between the two dyes due
      to their different solubilization sites and different impact on their
      microenvironment.

PMID- 15964577
TI  - Adsolubilization of toluene and acetophenone as a function of surfactant
      adsorption.
AB  - Adsolubilization, solubilization of organic compounds into adsorbed surfactant
      aggregates, has attracted much attention in the past few years. It is being
      explored for a variety of new commercial applications including the formation of
      engineered surfaces, pharmaceutical applications, and nanotechnology.
      Adsolubilization is strongly influenced by the amount of adsorbed surfactant,
      which in turn depends upon pH, ionic strength, and surfactant type and
      concentration. In this study, the adsorption of a cationic surfactant,
      cetyltrimethylammonium bromide (CTAB) on precipitated silica and the
      adsolubilization of organic solutes (toluene and acetophenone) into the adsorbed
      surfactant aggregates were examined as a function of surfactant adsorption at two
      pH values (5 and 8). Three levels of surfactant adsorption, corresponding to
      equilibrium concentration low in region II, high in region II, and low in region
      III of the adsorption isotherm, and the adsolubilization of toluene and
      acetophenone were investigated both in single- and mixed-solute systems. The
      results showed that the adsorption of CTAB depended strongly on pH and for each
      pH the adsolubilization increased with increasing surface adsorption. However,
      the adsolubilization behaviors of the adsorbed CTAB aggregates in different
      adsorption regions were quite distinct, suggesting that the structural
      arrangement of the surfactant aggregates may play an important part in addition
      to the amount of adsorbed surfactant. This phenomenon was more noticeable at low
      surfactant adsorption than at higher surface adsorption. In mixed-solute systems,
      the presence of acetophenone had little effect on the toluene adsolubilization.
      In contrast, a synergetic effect was observed in the adsolubilization of
      acetophenone in the presence of toluene.

PMID- 15964579
TI  - Fabrication of double-walled microspheres for the sustained release of
      doxorubicin.
AB  - Double-walled microspheres with poly(L-lactic acid) shells and poly(DL-lactic-co
      glycolic acid) cores were fabricated using solvent evaporation technique which
      involves the phase separation phenomenon of a binary composite of these two
      polymers. Doxorubicin, a hydrophilic drug, was entrapped within the core of these
      double-walled microspheres with different core-shell thicknesses and compositions
      to investigate the in vitro release on this class of microspheres. Microspheres
      of different size ranging from 50 to 300 microm were also fabricated to
      investigate whether this method is suitable for fabricating small particles for
      intramuscular injection applications, and their phase separation and surface
      morphology were examined by differential scanning calorimetry, scanning electron
      microscopy, and optical microscopy.

PMID- 15964580
TI  - Relaxation phenomena of hydrolyzed polyvinylamine molecules adsorbed at the
      silica/water interface II. Saturated heterogeneous polymer layers.
AB  - Surface area exclusion chromatography (SAEC) was employed to determine the
      individual relaxation of polymer molecules within a saturated heterogeneous layer
      composed of two polymers of different molecular characteristics. The
      investigations focused on three systems differing in molecular weight and/or
      hydrolysis grade. The molecular relaxation process was determined to be different
      within the heterogeneous layer when compared with the behavior of the same
      polymer in the homogeneous layer. The modifications in the relaxation process of
      a given polymer were imposed by the interfacial characteristics of the second
      polymer. Finally, in heterogeneous layers, the relative variation of the
      interfacial area of the two polymers is expressed in a single relationship.

PMID- 15964581
TI  - In vitro stability study of organosilane self-assemble monolayers and
      multilayers.
AB  - The stability of self-assembled monolayers (SAMs) and multilayers formed on
      silicon surface by amino-terminated silanes and SAMs formed by alkyl and glycidyl
      terminated silanes were investigated in vitro with saline solution at 37 degrees
      C for up to 10 days. FTIR and XPS results indicated that amino-terminated SAMs
      and multilayers are very unstable if the alkyl chain is short ((CH2)3), while
      stable if the alkyl chain is long ((CH2)11). On the other hand, alkyl-terminated
      SAMs are very stable regardless of the alkyl chain length, and glycidyl
      terminated SAM retained approximately 77% of the organosilane molecules after 10
      days. Hydrogen bonding between the organosilane monomer and silicon surface and
      among the organosilane monomers is believed to contribute to the instability of
      the SAM and multilayer formed by amino-terminated silane with a short alkyl chain
      ((CH2)3). Therefore, the widely used (3-aminopropyl) trimethoxysilane (APTMS) SAM
      and multilayer may not be suitable for implantable biomedical applications.

PMID- 15964582
TI  - Relaxation phenomena of hydrolyzed polyvinylamine molecules adsorbed at the
      silica/water interface III. Interfacial exchange and transfer processes.
AB  - Surface area exclusion chromatography (SAEC) was employed to determine the
      stability characteristics of saturated homogeneous layers when interfacial
      exchange or transfer of molecules was promoted. In these experiments, the first
      polymer layer was established by elution of a column composed of stacked glass
      fiber filters with one polymer. Then, after displacement of the void by water,
      the second polymer was subsequently injected under the same elution conditions.
      The experiments combine polymers of equal or different molecular weight and/or
      hydrolysis grade. Histograms of SAEC experiments demonstrate the great stability
      of the initially adsorbed layer. Domains of high and low adsorption values were
      determined to exist along the chromatography column after injection of the first
      polymer sample. The polymer injected second slightly modifies the initial
      adsorption histogram and mainly overadsorbs on the low adsorption domain of the
      first polymer. The major result relates to the relaxation phenomenon affecting or
      not the second adsorbed polymer when it adsorbs on filters belonging to the low
      adsorption domain of the polymer first injected. The relaxation is impeded when
      the relaxation of the first polymer is of great amplitude, whereas it occurs when
      the relaxation of the first polymer is small.

PMID- 15964583
TI  - Cluster aggregation and fragmentation kinetics model for gelation.
AB  - Gelation can occur in polymer, hydrogel, and colloid systems that undergo
      reversible aggregation-fragmentation (crosslinking accompanied by breakage).
      Gelation, characterized by rapid divergence of weight-average molecular weight
      and viscosity due to initial network formation, can be reversed if conditions
      change. In this paper, reversible aggregation and fragmentation in the pre
      gelation time period are modeled with distribution kinetics. Moment equations are
      obtained from the population balance equation, and solved for eight different
      rate kernels. We identify the cases for which gelation is possible and obtain the
      critical values for the rate constants that allow gelation. The model provides a
      good simulation of published experimental data for aggregation and degradation of
      plasticized wheat gluten during thermo-mechanical treatments. We also evaluate
      two closure approximations based on Gamma and log-normal distributions, and
      conclude that log-normal closure predicts all five possible steady states, in
      agreement with the Vigil-Ziff criterion, and Gamma closure predicts only three.
      However, Gamma closure approximates the steady state either closely or exactly,
      whereas log-normal closure only poorly approximates the steady-state
      distribution.

PMID- 15964584
TI  - Adsorption of fluoride, chloride, bromide, and bromate ions on a novel ion
      exchanger.
AB  - A novel ion exchanger based on double hydrous oxide (Fe2O3Al2O3xH2O) was obtained
      by the original sol-gel method from easily available and cheap raw materials and
      employed for adsorption of F-, Cl-, Br-, and BrO-3 from simultaneous solutions.
      Adsorbent was characterized by potentiometric titration, zeta-potential, and
      poremetrical characteristics. A technologically attractive pH effect of F-, Br-,
      and BrO-3 sorption on the investigated double hydroxide of Fe and Al, which is
      capable of working in the pH range 3 to 8.5, was observed. Kinetic data on
      fluoride and bromide sorption fit well the pseudo-second-order model. Isotherms
      of fluoride, bromide, chlorine, and bromate ion sorption on Fe2O3Al2O3xH2O were
      obtained at pH 4. The isotherm of F- sorption fit well the Langmuir model;
      sorption affinity (K=0.52 L/mg) and sorption capacity (90 mg F/g) were high. In
      the competitive adsorption of bromide and bromate, bromide dominated at
      equilibrium concentrations of the ions >40 mg/L. The mechanism of fluoride
      adsorption to the surface of the model cluster of the sorbent synthesized and the
      geometry of the cluster itself were modeled with the HyperChem7 program using the
      PM3 method.

PMID- 15964585
TI  - Electrokinetic and adsorption studies of alumina suspensions using Darvan C as
      dispersant.
AB  - The electrokinetic and adsorption characteristics of alumina suspensions in the
      presence of Darvan C as dispersant have been investigated. The interaction of
      Darvan C with alumina has been interpreted in terms of electrokinetic and
      adsorption measurements. The adsorption density of Darvan C increases greatly
      with decreasing pH. The isoelectric point (iep) of the sample under investigation
      is found to be located at pH 9.1. For pH values near and below the point of zero
      charge, there is an added electrostatic attractive potential for adsorption,
      which results in high-affinity adsorption behavior. Possible mechanisms of
      interaction between alumina and Darvan C are described and discussed.

PMID- 15964586
TI  - Stability of dispersions of colloidal alumina particles in aqueous suspensions.
AB  - The colloidal stability of suspensions of alumina particles has been investigated
      by measuring particle size distribution, sedimentation, viscosity, and zeta
      potential. Alumina particles were found to be optimally dispersed at pH around 3
      to 7.8 without dispersant and at pH 8.5 and beyond with dispersant. The above
      results corroborate zeta potential and viscosity measurement data well. The
      surface charge of alumina powder changed significantly with anionic
      polyelectrolyte (ammonium polycarboxylate, APC) and the iep shifted toward more
      acidic range under different dispersant conditions. It was found that the
      essential role played by pH and dispersant (APC) on the charge generation and
      shift in the isoelectric point of alumina manifests two features: (i) the
      stability decreases on approaching the isoelectric point from either side of pH,
      and (ii) the maximum instability was found at pH 9.1 for alumina only and at pH
      6.8 for alumina/APC, which is close to the isoelectric points for both the
      system, respectively. Using the model based on the electrical double-layer theory
      of surfactant adsorption through shift in isoelectric points, the authors could
      estimate the specific free energy of interaction (7.501 kcal/mol) between
      particles and dispersant. The interaction energy, zeta potential, sedimentation,
      and viscosity results, were used to explain the colloidal stability of the
      suspension.

PMID- 15964587
TI  - Ratings within and across ethnic boundaries of methods of one on one reading
      instruction.
AB  - Selected video segments of eight instructional sessions were evaluated by 39
      speech language pathologists (SLPs). Each involved one of four first grade female
      students at-risk for academic difficulties being instructed by an African
      American SLP. In half the videos instruction was focused on story content (whole
      language) and in the other half on form (sound-symbol correspondence). Raters
      judged the child's comprehension, and the clinician's clarity and enthusiasm.
      Videos appeared in a random order. Raters received no advance information about
      the orientation of instruction or demography. Two of the children were African
      Americans, one was Caucasian, and one Hispanic. All used American English as
      their home language. With respect to efficacy of methods, ratings significantly
      favored the content (whole language) orientation in agreement with an independent
      count of miscues and scores for story retelling. However, ratings across ethnic
      boundaries differed with quantitative measures suggesting possible stereotyping.
      LEARNING OUTCOMES: As a result of reading this article, participants will be able
      to (1) discuss factors that may color interactions with at-risk clients, (2)
      distinguish surface oriented (sound-symbol) approaches to reading instruction
      from content (meaning) oriented approaches, (3) describe influences of ethnicity
      on qualitative judgments crucial to clinical interactions.

PMID- 15964588
TI  - Effects of gadolinium chloride (GdCl(3)) on the appearance of macrophage
      populations and fibrogenesis in thioacetamide-induced rat hepatic lesions.
AB  - Macrophages infiltrating injured tissue play an important part in fibrogenesis.
      To shed light on the functional roles of macrophages, we investigated the
      appearance of macrophage populations in thioacetamide (TAA)-induced rat hepatic
      lesions, with or without pretreatment with GdCl(3), a chemical capable of
      inhibiting Kupffer cell functions. In the GdCl(3)+TAA group rats received a
      single intraperitoneal injection of GdCl(3) (7.5mg/kg body weight) and, after
      24h, a single intravenous injection of TAA (300mg/kg body weight). Rats in the
      TAA group received TAA only. Rats in both groups were examined on post-TAA
      injection (PTI) days 3, 5, and 7. In the TAA group, on PTI day 3, when TAA
      induced hepatocyte injury was particularly prominent, the number of macrophages
      peaked, subsequently decreasing until PTI day 7. As compared with the TAA group,
      the GdCl(3)+TAA group showed significantly decreased numbers of ED1
      immunolabelled cells (exudate macrophages) and ED2-immunolabelled cells (Kupffer
      cells) on PTI days 3, 5, and 7, and OX6-immunolabelled cells (antigen-presenting
      macrophages) on PTI days 3 and 5. Although less strikingly, the numbers of alpha
      smooth muscle actin-positive myofibroblasts and fibrotic areas were decreased in
      the GdCl(3)+TAA group. By RT-PCR, the expression of TGF-beta1 mRNA was suppressed
      on PTI days 3 and 7 in the GdCl(3)+TAA group, and the suppressed expression was
      confirmed in vitro by treating rat macrophage-like cells (HS-P) with 1% GdCl(3).
      The study showed that GdCl(3) treatment decreased the numbers of macrophages
      appearing in hepatic lesions and inhibited TGF-beta1 mRNA expression in
      macrophages. Decreased numbers of macrophages may contribute to improvement of
      hepatic fibrosis.

PMID- 15964589
TI  - Temporal progression of viral replication and gross and histological lesions in
      Balb/c mice inoculated epidermally with Saimiriine herpesvirus 1 (SaHV-1).
AB  - Saimiriine herpesvirus 1 (SaHV-1), an alphaherpesvirus enzootic in squirrel
      monkeys, is genetically related to monkey B virus and human herpes simplex virus
      (HSV). To study the temporal progression of viral spread and associated lesions,
      Balb/c mice were inoculated epidermally by scarification with a green fluorescent
      protein (GFP)-expressing recombinant strain of SaHV-1 and killed sequentially.
      Pinpoint ulcerative lesions in the inoculated epidermis progressed over a few
      days to unilateral or bilateral hindlimb paresis or paralysis, urinary and faecal
      incontinence, abdominal distension, hunched posture and eventual depression
      warranting euthanasia. Viral replication was present within epidermal
      keratinocytes, neurons of the dorsal root ganglia and thoracolumbar spinal cord,
      regional autonomic ganglia, lower urinary tract epithelium and colonic myenteric
      plexuses, as indicated by histological lesions and GFP expression. Almost all
      mice inoculated with 10(5) or 10(6) plaque-forming units (PFU) of SaHV-1
      developed rapidly progressive disease. Two of eight mice given 10(4)PFU developed
      disease, but no mice receiving less than 10(4)PFU gave evidence of infection.
      Mice that showed no clinical signs also failed to develop an antiviral IgG
      response, indicating absence of active viral infection. For SaHV-1 inoculated
      epidermally, the ID(50), CNSD(50) and LD(50) values were identical (10(4.38)),
      indicating that successful infection by this route invariably resulted in lethal
      CNS (central nervous system) disease. Consistently severe disease in all infected
      animals, with regionally extensive distribution of viral replication, constituted
      a marked difference from the disease produced by intramuscular inoculation.

PMID- 15964590
TI  - Synthetic peptide-derived antibody-based immunohistochemistry for the detection
      of porcine circovirus 2 in pigs with postweaning multisystemic wasting syndrome.
AB  - Porcine circovirus 2 (PCV2) was detected consistently in formalin-fixed paraffin
      wax-embedded lymph node and spleen from experimentally and naturally infected
      pigs by synthetic peptide-derived polyclonal antibody-based immunohistochemistry.
      Synthetic peptides were generated from open reading frame 2 of PCV2 by solid
      phase peptide synthesis, purified by high performance liquid chromatography, and
      injected into rabbits to produce polyclonal antibody. Positive cells had large
      nuclei with abundant cytoplasm, and resembled macrophages. In serial sections, a
      similar distribution of PCV2 antigen and DNA was confirmed in virus-infected
      cells by immunohistochemistry and in-situ hybridization, respectively. The
      immunohistochemical method described was successfully applied to formalin-fixed,
      paraffin wax-embedded tissues and should prove helpful in diagnosing postweaning
      multisystemic wasting syndrome.

PMID- 15964591
TI  - Responses to sex pheromone and plant odours by olfactory receptor neurons housed
      in sensilla auricillica of the codling moth, Cydia pomonella (Lepidoptera:
      Tortricidae).
AB  - Antennal olfactory receptor neurons located in a limited number of two types of
      sensilla auricillica, the rabbit-eared shoehorn and the regular shoehorn, located
      on the 5-30 flagellomere of the codling moth, Cydia pomonella, antenna were
      screened for selectivity to 11 plant compounds, the major sex pheromone
      component, three minor pheromone components and one behavioural antagonist. Both
      types of sensilla housed at least three neurons characterised by different action
      potential amplitudes. Neurons in both males and females responded to the plant
      compounds, ethyl (E,Z)-2,4-decadienoate, (+/-)-linalool, (E)-ss-farnesene,
      hexanol, (Z)-3-hexenyl acetate, 4,8-dimethyl-1,3,(E)7-nonatriene, nonanol, the
      major pheromone component codlemone [(E,E)-8,10-dodecadienol] and the minor
      pheromone component tetradecanol. Additionally, (E,E)-alpha-farnesene and (Z)-3
      hexenol elicited responses specifically in female neurons, whereas (E,E)-farnesol
      elicited a specific response in a male neuron. Neurons responded to 1-3 odorants,
      with sometimes overlapping response spectra. A scanning electron microscopic
      study of the antennae of both sexes supported an earlier study, apart from that
      long s. trichodea were present in a wreath at the proximal margin of the
      flagellomere and in addition evenly distributed over the remaining surface, and a
      previously non-described sensillum type with external basiconic features was
      revealed, distributed on the proximal and medial region of the flagellomeres.

PMID- 15964592
TI  - Dissecting the variance-covariance structure in insect physiology: the
      multivariate association between metabolism and morphology in the nymphs of the
      sand cricket (Gryllus firmus).
AB  - Energy metabolism in animals has been largely studied in relation to exogenous
      sources of variation. However, because they give insight into the relationship
      between whole metabolism and lower organizational levels such as organs and
      tissues, examination of endogenous determinants of metabolism other than body
      mass is itself very important. We studied the multivariate association of body
      parts and several aspects of energy metabolism in an insect, the nymphs of the
      sand cricket, Gryllus firmus. By using a variety of both univariate and
      multivariate techniques, we explored the resultant variance-covariance matrix to
      build a path diagram with latent variables. After controlling for body mass, we
      found a significant canonical correlation between metabolism and morphology.
      According to the factor loadings and path coefficients, the most important
      contributions of morphology to the correlation were thorax and abdomen size
      measures, whereas the most important metabolic contribution was resting
      metabolism. Activity metabolism was mostly explained by body mass rather than
      body parts, which could be a result of resting rates being chronic consequences
      of the functioning of the metabolic machinery that the insect must maintain.

PMID- 15964593
TI  - Chronic antipsychotics treatment regulates MAOA, MAOB and COMT gene expression in
      rat frontal cortex.
AB  - Chronic antipsychotic drugs treatment may regulate the expression of a variety of
      genes in the brain, which may underscore their clinical efficacy and/or side
      effects. In this study, we measured the mRNA levels of three genes encoding the
      catabolic enzymes of biogenic amine neurotransmitters, i.e., monoamine oxidase A
      (MAOA), B (MAOB) and catechol O-methyltransferase (COMT), in rat frontal cortex
      following 4 weeks' treatment of various antipsychotic drugs using quantitative
      PCR. Significantly elevated mRNA levels of MAOB and COMT were first observed in
      frontal cortex of rats treated with risperidone (1mg/kg) when compared to control
      animals. Further study showed that chronic treatment of olanzapine (2mg/kg), but
      not haloperidol (1mg/kg) or clozapine (20mg/kg), resulted in significantly
      increased mRNA levels of MAOA, MAOB and COMT in rat frontal cortex as compared to
      control animals. These results indicate that chronic treatment of different
      antipsychotic drugs may differentially regulate the gene expression of three
      catabolic enzymes of biogenic amine neurotransmitters, and which may partly
      account for the molecular mechanism of their different clinical efficacy.

PMID- 15964594
TI  - A prospective study of the psychological effects of "person under train"
      incidents on drivers.
AB  - Previous studies have shown that person under train (PUT) accidents cause
      psychological distress to drivers during the first year following the incident.
      Our aims were to assess the psychological consequences of PUT accidents on
      drivers prospectively, and to identify risk factors for psychological effects. In
      this prospective, one-year, follow-up study, a consecutive series of PUT drivers
      (n=202) were compared with a group of matched control drivers (n=186).
      Psychological state was assessed 15 days, 3 months and 1 year after the event,
      using the GHQ-28 questionnaire and a standardised diagnostic interview (the v4.4
      MINI). Fifteen days after the event, PUT drivers had significantly higher GHQ-28
      scores (p<0.0001) and more acute stress disorder (p=0.008) than control drivers.
      No significant differences were found 3 months and 1 year after the accident.
      Significant explicative variables were the presence of acute and chronic
      psychosocial stressors (OR=3.30 and 3.68) and the availability of immediate help
      (OR=0.46). We thus confirm previous findings that train drivers who have
      experienced a PUT accident experience acute psychological disturbances. Our
      results also highlight the utility of the systematic prevention programme
      provided.

PMID- 15964595
TI  - Transcranial magnetic stimulation in the treatment of schizophrenic symptoms: a
      double blind sham controlled study.
AB  - BACKGROUND: Schizophrenia is a disabling disease with a significant proportion of
      patients experiencing persistent symptoms. Repetitive transcranial magnetic
      stimulation (rTMS) is a promising new therapeutic tool that could benefit to
      schizophrenic patients. In this study we sought to assess the efficacy of active
      rTMS compared to sham stimulation in the treatment of patients with
      schizophrenia. METHOD: Eighteen schizophrenic patients according to DSM-IV
      criteria were randomly allocated to receive active or sham rTMS for 10 days over
      the left temporoparietal cortex (80% of the motor threshold, 1Hz, five trains of
      1 min). Psychopathological dimensions were measured with the positive and
      negative syndrome scale and clinical global impression at baseline and after 10
      session of rTMS. RESULTS: All patients were improved at the end of the trial but
      no significant group differences were found. Patients receiving sham stimulation
      showed the same pattern of improvement compared to active condition on all the
      subscales of the positive and negative syndrome scale and clinical global
      impression scores (p>0.05). CONCLUSION: In our study, active rTMS failed to show
      superiority over sham stimulation in the treatment of schizophrenic symptoms.
      Although previous results have shown that rTMS reduces auditory hallucination,
      its efficacy on other positive schizophrenic symptoms is not yet established.
      Nevertheless, the results of our study, even though negative, provide further
      insights in the pathophysiology of schizophrenia.

PMID- 15964596
TI  - Developmental changes of the expression of the genes regulated by retinoic acid
      in the small intestine of rats.
AB  - Retinoic acid (RA) serves as a hormone-like nutrient and it plays pivotal roles
      in cellular differentiation and proliferation in various tissues including the
      small intestine. In this study, we aimed to explore a possible role of RA
      signaling in the developing rat small intestine of perinatal (embryonic and
      newborn) and suckling-weaning transition period, and we investigated the changes
      in the expression of several genes regulated by RA. Northern blot analysis showed
      that both retinal dehydrogenase 1 (RALDH1) and retinal dehydrogenase 2 (RALDH2)
      mRNA levels were higher in 19-day fetal (2 days before birth) small intestine and
      then declined after birth. Retinoid X receptor alpha (RXRalpha) mRNA and retinoic
      acid receptor alpha (RARalpha) mRNA levels in the small intestine showed high
      levels in perinatal period compared with suckling-weaning transition period. RA
      target genes such as retinoic acid receptor beta (RARbeta) and cellular retinol
      binding protein, type II (CRBPII) mRNA levels were significantly increased in the
      perinatal small intestine. Furthermore, mRNA levels of hepatocyte nuclear factor
      4 (HNF-4), which is one of the possible RA-target gene and a transcription factor
      regulating CRBPII gene expression, was also increased in the perinatal small
      intestine. These results suggest that the possible perinatal RA production by
      RALDHs might regulate various RA-target genes including CRBPII and RARalpha
      through RXRalpha or HNF-4 in the small intestine.

PMID- 15964597
TI  - Metformin treatment restores the altered microvascular reactivity in neonatal
      streptozotocin-induced diabetic rats increasing NOS activity, but not NOS
      expression.
AB  - Abnormalities in vascular function are well recognized in diabetes. Hyperglycemia
      may be central to the pathogenesis of vascular dysfunction but is not certain
      whether improvements in glycaemic control will improve vascular function. The
      effects of metformin, an antidiabetic agent that improves insulin sensitivity and
      glycaemic control, on the microvascular reactivity have not been reported in
      neonatal streptozotocin-induced (n-STZ) diabetes. Diabetes was induced by STZ
      injection (160 mg/kg, ip) in neonates (2-day-old) Wistar rats. n-STZ diabetic
      rats were treated with metformin (300 mg/kg, 15 d, by gavage). Using intravital
      microscopy the changes in mesenteric arteriolar and venular diameters were
      determined in anesthetized control and n-STZ diabetic rats, before and after
      topical application of endothelium-dependent vasodilator agents, mediators or not
      of the inflammatory response, and endothelium-independent vasodilator agent. We
      also determined the total nitric oxide synthase (NOS) activity (conversion of L
      arginine to citrulline) and endothelial(e), inducible(i), and neuronal(n) NOS
      expression (using polymerase chain reaction after reverse transcription of the
      mRNAs into cDNAs) in the mesentery of metformin-treated n-STZ diabetic and
      vehicle-treated n-STZ diabetic and control rats. Although metformin treatment did
      not correct the high glycaemic levels and the impaired glucose tolerance, the
      reduced vasodilator responses and total NOS activity in n-STZ diabetic rats were
      corrected by the treatment. Neither diabetes nor metformin treatment altered the
      expression of the three NOS isoforms. We concluded that metformin restores the
      reduced response to vasodilator agents, independently of the correction of the
      metabolic alterations. Improvement of total NOS activity might be in part
      responsible for the correction.

PMID- 15964598
TI  - G80A reduced folate carrier SNP modulates cellular uptake of folate and affords
      protection against thrombosis via a non homocysteine related mechanism.
AB  - Dietary folate is absorbed in the jejunum by the 'Reduced Folate Carrier' binding
      protein. This protein also sequesters extracellular folate for use by many cells
      in the body. As several biosynthetic pathways require folate for critical life
      processes, any change in the properties of this protein could lower folate
      bioavailability, cellular levels of the vitamin, and thus influence health. Since
      folate lowers thrombogenic homocysteine, we examined the prevalence of a common
      genetic polymorphism encoding the Reduced Folate Carrier (G80A RFC) to see if it
      acts as a risk factor for thrombotic vascular disease via an effect on
      homocysteine disposition in a cohort of 156 patients. The odds ratio indicates a
      significant protective effect of the mutant A allele against thrombosis: OR =
      0.56(95% CI; 0.34-0.92). chi2; p = 0.022 (Yates corrected chi2; p = 0.031). The
      polymorphism had no impact on homocysteine, but did increase the level of
      extracellular to intracellular folate as might be predicted by the biological
      role of the expressed protein. This, and not homocysteine level, may be what
      affords protection against thrombosis.

PMID- 15964599
TI  - Enhancing the uptake of dextromethorphan in the CNS of rats by concomitant
      administration of the P-gp inhibitor verapamil.
AB  - Clinical trials evaluating high doses of dextromethorphan hydrobromide (DM) for
      the treatment of neurological disorders have resulted in numerous adverse events
      due to the presence of its active metabolite dextrorphan (DX). Since the uptake
      of drugs in the CNS can be modulated by P-glycoprotein (P-gp) inhibition at the
      blood-brain barrier (BBB), we propose to determine whether the P-gp inhibitor
      verapamil can enhance the uptake of DM in the CNS. Rats (n=42) received an oral
      dose of DM (20 mg/kg) alone or 15 min after an intravenous dose of verapamil (1
      mg/kg). Rats were euthanized at different time points over 12 h, and
      concentrations of DM and DX (conjugated and unconjugated) were assessed in
      plasma, brain and spinal cord using a LC-ESI/MS/MS method. Pharmacokinetic
      parameters were calculated using noncompartmental methods. Verapamil treatments
      did not affect the biodisposition of DM in plasma. On the other hand, verapamil
      treatments increased the area under curve of DM in the brain (from 1221 to 2393
      ng h/g) and spinal cord (from 1753 to 3221 ng h/g) by approximately 2-fold. The
      uptake of DX in brain and spinal cord were markedly lower than those of DM and
      increased by only 15% and 22% following verapamil treatments, respectively. These
      results suggest that the P-gp inhibitor verapamil can enhance the uptake of DM in
      the CNS without affecting that of DX. This change is most likely related to an
      inhibition of P-gp or other transporters located in the BBB since the
      biodisposition of DM in plasma remained unaffected by verapamil treatments.

PMID- 15964600
TI  - Effects of emodin treatment on mitochondrial ATP generation capacity and
      antioxidant components as well as susceptibility to ischemia-reperfusion injury
      in rat hearts: single versus multiple doses and gender difference.
AB  - Effects of emodin (EMD) treatment on mitochondrial ATP generation capacity and
      antioxidant components as well as susceptibility to ischemia-reperfusion (I-R)
      injury were examined in male and female rat hearts. Isolated-perfused hearts
      prepared from female rats were less susceptible to I-R injury than those of male
      rats. I-R caused significant decreases in ATP generation capacity and reduced
      glutathione (GSH) and alpha-tocopherol (alpha-TOC) levels as well as glutathione
      reductase, Se-glutathione peroxidase and Mn-superoxide dismutase (SOD)
      activities. The lower susceptibility of female hearts to myocardial I-R injury
      was associated with higher levels of GSH and alpha-TOC as well as activity of SOD
      than those of male hearts. EMD treatment at 3 daily doses (0.6 or 1.2 mmol/kg)
      could enhance myocardial mitochondrial ATP generation capacity and antioxidant
      components in both male and female rat hearts, but it only significantly
      protected against I-R injury in female hearts. Treatment with a single dose of
      EMD invariably enhanced mitochondrial antioxidant components and protected
      against I-R injury in both male and female hearts. The gender-dependent effect of
      EMD treatment at multiple doses may be related to the differential antioxidant
      response in the myocardium and/or induction of drug metabolizing enzymes in the
      liver.

PMID- 15964601
TI  - A method to determine which nutrient is limiting for plant growth in estuarine
      waters--at any salinity.
AB  - A method, utilising overlaid graphs for nutrients vs salinity, was developed in
      order to determine which nutrient is limiting for plant growth in estuarine
      waters-at any salinity. Dissolved inorganic nitrogen (DIN=NO(3)(-)+NO(2)(
      )+NH(4)(+)) and o-phosphate (PO(4)(-)) are the main forms of N and P that are
      readily bio-available for plant growth in waters and these have a Redfield atomic
      ratio of N:P=16:1 (i.e. aquatic plants absorb N and P in the average ratio of 16
      atoms of N to 1 atom of P). Graphs are prepared for (i) DIN vs salinity and (ii)
      o-phosphate vs salinity with the vertical scales for DIN and o-phosphate set at a
      ratio of N:P=16:1; when these graphs are overlaid on each other then the
      lowermost trendline denotes the limiting nutrient for plant/algal growth-at any
      salinity. The graphs also indicate the extent by which one or other of the
      nutrients is limiting--at any salinity. Furthermore, if there is a transition
      from P to N limitation somewhere along the salinity gradient, then this occurs at
      the salinity where the trendlines intersect. The concept was applied to three
      estuaries in the southeast of Ireland and the results show that, in all of these
      circumstances, P is the limiting nutrient throughout--except for the higher
      salinities (i.e. salinities 30 per thousand), where either (i) N and P may become
      equally limiting at salinity approximately 35 per thousand or (ii) N may become
      limiting at salinity 30 per thousand. Overlaid nutrients vs salinity graphs were
      also used to demonstrate that, in the estuaries in southeast Ireland, carbon (as
      dissolved inorganic carbon, DIC=CO(2)+H(2)CO(3)+HCO(3)(-)+CO(3)(2-)) is not the
      limiting nutrient--at any salinity.

PMID- 15964602
TI  - Imidazenil: an antagonist of the sedative but not the anticonvulsant action of
      diazepam.
AB  - Flumazenil (FLU), a specific benzodiazepine (BZ) receptor antagonist has been
      used in the treatment of acute BZ intoxication or the alleviation of BZ-induced
      withdrawal syndrome on the basis of its weak partial agonist action at GABA(A)
      receptors. However, given to patients, FLU can worsen diazepam-induced withdrawal
      syndrome by lowering seizure threshold. We therefore investigated whether
      imidazenil, a selective positive allosteric modulator of GABA action at GABA(A)
      receptors containing alpha5 subunit, can antagonize diazepam-induced sedative
      action and suppression of locomotor activity without affecting diazepam anti
      bicuculline action. We report here that while FLU (16.5 micromol/kg) showed no
      effect on locomotor activity and bicuculline-induced convulsion, it completely
      antagonized diazepam (10.5 micromol/kg) anti-bicuculline action and the
      suppression of locomotor activity. However, imidazenil (0.76 micromol/kg)
      elicited anti-bicuculline action and was dose-dependently antagonized by FLU
      (16.5 and 33 micromol/kg). Furthermore, imidazenil showed no effect on path
      length traveled but slightly decreased (40%) horizontal activity when compared to
      diazepam (85%), and maintained the anti-bicuculline action of diazepam to a
      threshold level similar to that observed with diazepam. Whereas cross-tolerance
      between BZs has been reported in animals and humans, we previously reported the
      absence of cross-tolerance between imidazenil and diazepam. Thus, we suggest that
      imidazenil might be more effective than FLU at alleviating the withdrawal
      syndrome associated with long-term BZ administration.

PMID- 15964603
TI  - Differential ion current activation by human 5-HT(1A) receptors in Xenopus
      oocytes: evidence for agonist-directed trafficking of receptor signalling.
AB  - The subject of the present study was the functional and pharmacological
      characterization of human 5-HT(1A) receptor regulation of ion channels in Xenopus
      oocytes. Activation of the heterologously expressed human 5-HT(1A) receptor
      induced two distinct currents in Xenopus oocytes, consisting of a smooth inward
      current (I(smooth)) and an oscillatory calcium-activated chloride current,
      I(Cl(Ca)). 5-HT(1A) receptor coupling to both ionic responses as well as to co
      expressed inward rectifier potassium (GIRK) channels was pharmacologically
      characterized using 5-HT(1A) receptor agonists. The relative order of efficacy
      for activation of GIRK current was 5-HT approximately F 13714 approximately L
      694,247 approximately LY 228,729>flesinoxan approximately (+/-)8-OH-DPAT. In
      contrast, flesinoxan and (+/-)8-OH-DPAT typically failed to activate I(Cl(Ca)).
      The other ligands behaved as full or partial agonists, exhibiting an efficacy
      rank order of 5-HT approximately L 694,247>F 13714 approximately LY 228,729. The
      pharmacological profile of I(smooth) activation was completely distinct:
      flesinoxan and F 13714 were inactive and rather exhibited an inhibition of this
      current. I(smooth) was activated by the other agonists with an efficacy order of
      L 694,247>5-HT approximately LY 228,729>(+/-)8-OH-DPAT. Moreover, activation of
      I(smooth) was not affected by application of pertussis toxin or the non
      hydrolyzable GDP-analogue, guanosine-5'-O-(2-thio)-diphosphate (GDP betaS),
      suggesting a GTP binding protein-independent pathway. Together, these results
      suggest the existence of distinct and agonist-specific signalling states of this
      receptor.

PMID- 15964604
TI  - Isolation of a genotypically unique H5N1 influenza virus from duck meat imported
      into Japan from China.
AB  - An H5N1 influenza A virus was isolated from duck meat processed for human
      consumption, imported to Japan from Shandong Province, China in 2003. This virus
      was antigenically different from other H5 viruses, including the Hong Kong H5N1
      viruses isolated from humans in 1997 and 2003. Sequence analysis revealed that
      six genes (PB1, PA, HA, NA, M, and NS) of this virus showed >97% nucleotide
      identity with their counterparts from recent H5N1 viruses, but that the remaining
      two genes (PB2 and NP) were derived from other unknown viruses. This duck meat
      isolate was highly pathogenic to chickens upon intravenous or intranasal
      inoculation, replicated well in the lungs of mice and spread to the brain, but
      was not as pathogenic in mice as H5N1 human isolates (with a dose lethal to 50%
      of mice (MLD50)=5x10(6) 50% egg infectious doses [EID50]). However, viruses
      isolated from the brain of mice previously infected with the virus were
      substantially more pathogenic (MLD50=approximately 10(2) EID50) and possessed
      some amino acid substitutions relative to the original virus. These results show
      that poultry products contaminated with influenza viruses of high pathogenic
      potential to mammals are a threat to public health even in countries where the
      virus is not enzootic and represent a possible source of influenza outbreaks in
      poultry.

PMID- 15964605
TI  - Complete genome sequence analysis of an iridovirus isolated from the orange
      spotted grouper, Epinephelus coioides.
AB  - Orange-spotted grouper iridovirus (OSGIV) was the causative agent of serious
      systemic diseases with high mortality in the cultured orange-spotted grouper,
      Epinephelus coioides. Here we report the complete genome sequence of OSGIV. The
      OSGIV genome consists of 112,636 bp with a G+C content of 54%. 121 putative open
      reading frames (ORF) were identified with coding capacities for polypeptides
      varying from 40 to 1168 amino acids. The majority of OSGIV shared homologies to
      other iridovirus genes. Phylogenetic analysis of the major capsid protein,
      ATPase, cytosine DNA methyl transferase and DNA polymerase indicated that OSGIV
      was closely related to infectious spleen and kidney necrosis virus (ISKNV) and
      rock bream iridovirus (RBIV), but differed from lymphocytisvirus and ranavirus.
      The determination of the genome of OSGIV will facilitate a better understanding
      of the molecular mechanism underlying the pathogenesis of the OSGIV and may
      provide useful information to develop diagnosis method and strategies to control
      outbreak of OSGIV.

PMID- 15964607
TI  - Molar microwear and dietary reconstructions of fossil cercopithecoidea from the
      Plio-Pleistocene deposits of South Africa.
AB  - The South African Plio-Pleistocene cave deposits have yielded a diverse
      cercopithecoid fauna. In this study, the possible dietary proclivities of these
      extinct species are examined using details of molar microwear. Although sample
      sizes are often small, wear patterns suggest possible temporal changes in the
      diets of Parapapio jonesi from Makapansgat to Sterkfontein, of Papio robinsoni
      from Sterkfontein to Swartkrans, and Cercopithecoides williamsi from Makapansgat
      to Sterkfontein to Swartkrans. However, there does not appear to have been a
      significant change in the dietary habits of Parapapio broomi over time. The
      microwear patterns of the two temporally successive congeners, Theropithecus
      darti and T. oswaldi show no significant differences from one another. The
      sympatric congeners, Parapapio broomi and Pp. jonesi, have microwear signatures
      that differ significantly at Makapansgat (Members 3 and 4) but not at
      Sterkfontein (Member 4). Finally, the microwear analyses suggest that the extinct
      cercopithecoid species did not necessarily have diets similar to those of their
      closest living relatives.

PMID- 15964606
TI  - Simulating the performance of fixed-bed granular activated carbon adsorbers:
      removal of synthetic organic chemicals in the presence of background organic
      matter.
AB  - Granular activated carbon (GAC) adsorption is an effective treatment technology
      for the removal of synthetic organic chemicals (SOCs) from drinking water
      supplies. This treatment process can be expensive if not properly designed.
      Application of mathematical models is an attractive method to evaluate the impact
      of process variables on process design and performance. Practical guidelines were
      developed to select an appropriate model framework and to estimate site-specific
      model parameters to predict GAC adsorber performance. Pilot plant and field-scale
      data from 11 different studies were utilized to investigate the effectiveness of
      this approach in predicting adsorber performance in the presence of background
      organic batter (BOM). These data represent surface and ground water sources from
      four different countries. The modeling approach was able to adequately describe
      fixed-bed adsorber performance for the purpose of determining the carbon usage
      rate and process design variables. This approach is more accurate at predicting
      bed life in the presence of BOM than the current methods commonly used by
      practicing engineers.

PMID- 15964608
TI  - Newly recognized Pleistocene human teeth from Tabun Cave, Israel.
AB  - Seven human teeth from Tabun Cave, Israel, curated at the Natural History Museum
      London since 1955, are of uncertain provenance and identity. They are all from
      the upper dentition, without duplications, and are characterized by a similar
      preservation. The Catalogue of Fossil Hominids (1975) suggested that they might
      have derived from Tabun Layer A (Bronze Age to Recent). However, one of us (AC)
      noted some distinctive features of these teeth that warranted further study. They
      are here assigned to a single individual, Tabun BC7. Their morphology and metrics
      were then compared with the frequency of Late Pleistocene and Early Holocene
      groups from Europe, North Africa and Middle East. A fragment of the right M3
      crown of Tabun BC7 was removed for ESR and U-analysis, and it was determined that
      only samples from Layer B have similar dose values. Using the sediment dose
      values of layer B, preliminary age estimates of 82 +/- 14 ka (early U-uptake) and
      92+/-18 ka (linear uptake) were obtained. U-series disequilibrium determined from
      other samples attributed to Layer B resulted in a U-uptake history close to
      linear uptake, giving a very comparable age estimate of 90(+30)(-16) ka. The dose
      value previously obtained on an enamel fragment from the Tabun C1 dentition is
      nearly double the value measured for BC7, and tentative age estimates for C1 were
      in the range of 143+/-37 ka. However, due to uncertainties in the exact
      provenance of the human fossils, we cannot confirm that C1 is older than the new
      tooth sampled here, and both C1 and BC7 can be attributed to Layer B on
      chronological grounds. On the basis of chronology, dental morphology and metrics,
      the specimen named Tabun BC7 was identified as a probable Neanderthal.

PMID- 15964609
TI  - "15 Minutes Of Fame": exploring the temporal dimension of middle pleistocene
      lithic technology.
AB  - This paper addresses the spatial and temporal dimensions of knapping routines
      through analysis of refit data. Many reconstructions of lithic tool production
      utilising refit data concentrate upon 'how' a piece of stone is taken apart, and
      less often consider the 'when' and 'where'. Lower Palaeolithic artefacts are
      frequently viewed as belonging to simplistic technical systems in which tools
      were made and used as and when required, showing little temporal depth. Modern
      knappers can replicate the components of the Acheulean toolkit, such as a biface,
      in around 15 minutes. The predominant use of local raw materials and the
      relatively simple reduction sequences observed on many Middle Pleistocene sites
      has given rise to the view that Acheulean hominins possessed an immediate
      approach to technology, and that artefacts did not stay in the technological
      system very long. In contrast, other researchers have stressed the increased
      planning abilities of hominins in relation to their stone tool-making and using
      routines. Increased planning abilities are often cited as a diagnostic feature of
      modern human cognition. As such, tracing the emergence of these abilities is an
      important avenue of research in human evolution. The aim of this paper is to
      investigate how the process of lithic production was organised on several Middle
      Pleistocene sites in northwest Europe. By comparing refitting sequences from
      several primary context sites, the different stages of reduction present at these
      locations can be reconstructed. Since refit sets record the work carried out in
      one place and time by an individual, they can be used to reconstruct the spatial
      and temporal dimension of these past technological activities. The analysis shows
      fragmentation of reduction sequences was a common occurrence, suggesting a more
      dynamic approach to tool-making and using activities than has previously been
      recognised. The analysis provides a description of these artefact dynamics, and
      discusses the underlying cognitive mechanisms of this behaviour.

PMID- 15964610
TI  - Ecological risk assessment on a cadmium contaminated soil landfill--a preliminary
      evaluation based on toxicity tests on local species and site-specific
      information.
AB  - In recent years, methodology of ecological risk assessment has been developed and
      applied frequently for addressing various circumstances where ecological impacts
      are suspected or have occurred due to environmental contamination; however, its
      practice is very limited in Taiwan. In 1982, brown rice from rice paddy fields in
      Da-Tan, Tau-Yuan, was found to be contaminated with Cd and Pb due to illegal
      discharges of wastewater, known as the "Cd rice" incidence. Cadmium laden soil
      was transferred to a constructed landfill in an industrial park 15 years after
      the incident. Possible leakage of the landfill was suspected by committee members
      of a supervising board for the remediation process, and a preliminary ecological
      risk evaluation was requested. A possible risk scenario was that groundwater
      contamination due to the leachate containing Cd and Pb from the landfill could
      result in pollution of coastal water, and subsequently produce toxic effects to
      aquatic organisms. Chemical dissipation in groundwater systems was simulated and
      short-term chronic toxicity tests on larvae of three local aquatic species were
      also performed to determine the no-observed adverse-effect concentrations
      (NOAECs), as well as the predicted no effect concentrations (PNECs), of the two
      metals in the organisms tested. The hazard quotient (HQ), the ratio of predicted
      environmental concentrations (PECs) to PNECs, was used for risk characterization.
      A worst-case-scenario calculation showed that the maximum Cd concentration at 60
      m and farther downstream from the site in the groundwater system would be 0.0028
      mg l(-1) with a maximum initial concentration of 0.65 mg l(-1) in the leachate,
      while for Pb, the highest concentration of 0.044 mg l(-1) would be reached at a
      distance of 40 m and farther, which was based on an initial concentration of 4.4
      mg l(-1) in the leachate; however, both cases would only occur 80 years after the
      initiation of leakage. A presumed dilution factor of 100 was used to calculate
      the PECs based on the maximum initial concentrations. The Cd and Pb's PNECs for
      three aquatic animals were 0.01 to approximately 0.1 mg l(-1), higher than their
      PECs in coastal water, resulting in HQs less than 1 for the scenario described.
      We concluded that if a leakage does occur, the ecological impact would be minimal
      because a majority of the metals will be retained in the soil phase and the
      remaining, if released into the aquatic system, cannot reach high enough
      concentrations to produce toxicity to marine animals.

PMID- 15964611
TI  - The spatial and temporal trends of Cd, Cu, Hg, Pb and Zn in Seine River
      floodplain deposits (1994-2000).
AB  - Fresh floodplain deposits (FD), from 11 key stations, covering the Seine mainstem
      and its major tributaries (Yonne, Marne and Oise Rivers), were sampled from 1994
      to 2000. Background levels for Cd, Cu, Hg, Pb, and Zn were established using
      prehistoric FD and actual bed sediments collected in small forested sub-basins in
      the most upstream part of the basin. Throughout the Seine River Basin, FD contain
      elevated concentrations of Cd, Cu, Hg, Pb and Zn compared to local background
      values (by factors>twofold). In the Seine River Basin, trace element
      concentrations display substantial downstream increases as a result of increasing
      population densities, particularly from Greater Paris (10 million inhabitants),
      and reach their maxima at the river mouth (Poses). These elevated levels make the
      Seine one of the most heavily impacted rivers in the world. On the other hand,
      floodplain-associated trace element levels have declined over the past 7 years.
      This mirrors results from contemporaneous suspended sediment surveys at the river
      mouth for the 1984-1999 period. Most of these temporal declines appear to reflect
      reductions in industrial and domestic solid wastes discharged from the main
      Parisian sewage plant (Seine Aval).

PMID- 15964612
TI  - Plasma levels of DDT and their association with reproductive hormones in adult
      men from northern Thailand.
AB  - Historically, dichlorodiphenyltrichloroethane (DDT) was used in northern Thailand
      for malaria control and farming purposes. Several studies have investigated its
      effects on end points of adverse reproductive health outcomes. However, the few
      previous studies investigated hormonal effects in men and available data are
      inconclusive. The authors aimed to explore the main hypothesis that plasma DDT
      levels in adult men were associated with reproductive hormone levels. A cross
      sectional study was performed of 97 adult men living in a highland village named
      Mae Sa Mai, 35 km north of Chiang Mai, Thailand. Venous blood samples were
      collected for measuring plasma levels of DDT and its metabolites and reproductive
      hormones, including 17beta-estradiol (E2), testosterone, luteinizing hormone
      (LH), and follicle stimulating hormone (FSH). 1,1-Dichloro-2,2-di(4
      chlorophenyl)ethylene (p,p'-DDE) and 1,1,1-trichloro-2,2-di(4-chlorophenyl)ethane
      (p,p'-DDT) were detected in all plasma samples. p,p'-DDE had the highest level
      with a median of 4057.7 ng/g lipids and a relatively higher level compared with
      most other studies. Plasma p,p'-DDT levels were positively associated with years
      of residence (beta+SE=0.472+0.208, P=0.028) and years of DDT usage for farming
      (beta+SE=0.177+0.084, P=0.04). The remarkable findings were the negative
      association of plasma E2 levels with plasma p,p'-DDE levels (beta+SE=
      7.093+2.899, P=0.016) and the positive association with plasma 1,1-dichloro-2-(2
      chlorophenyl)-2-(4-chlorophynyl)ethylene (o,p'-DDE) levels (beta+SE=16.381+5.596,
      P=0.008) after adjusting for age and body mass index (BMI). However, these
      associations were rather weak. Our results suggest that these associations may
      reflect their different mechanisms of hormonal activities and they would be
      warrant further detail investigations.

PMID- 15964613
TI  - Histological and histochemical assessment of the effects of a single dose
      adriamycin on fetal rat kidney.
AB  - Adriamycin (ADR) induces nephritic syndrome (NS) in adult rats. Therefore,
      effects of ADR in a single dose of 5mg/kg body weight given intraperitoneally to
      the mothers at 4 weeks before pregnancy were assessed on fetal rat kidneys in the
      present study. It induces increased amounts of PAS(+)-positive mesangial matrix,
      glomerulosclerosis, dilatation of the urinary space and thickening of basement
      membranes in glomeruli. In tubules, it damages or completely destroys epithelial
      cells, it induces dilatation of the tubular lumen and disintegration of the brush
      border. Changes in fetal rat kidney as observed light microscopically appeared to
      be similar to those described in kidneys of adult rats with NS induced by
      adriamycin, but were less distinct.

PMID- 15964614
TI  - Protective effects of a calcium channel blocker on apoptosis in thymus of
      neonatal STZ-diabetic rats.
AB  - Streptozotocin (STZ) is known to induce insulin-dependent diabetes in
      experimental animals. In STZ-induced diabetes, atrophy of the thymus is caused by
      elevated intracellular calcium levels leading to apoptosis. Hyperglycemia is
      known to result in a decrease in numbers of T cells in the thymus and
      circulation. Intracellular calcium levels increase in diabetic animals after
      induction by STZ. Hyperglycemia inhibits Ca2+-ATPase and increases intracellular
      calcium levels. We have investigated apoptosis in thymus tissue of neonatal STZ
      (n-STZ)-diabetic rats and the effects of isradipine as a calcium channel blocker
      (CCB) on apoptosis. Five groups of newborn Wistar rats were used. On the second
      day after birth, 100 mg/kg STZ was given i.p. to the first two groups. The first
      group was n-STZ diabetic. To the second group, starting from the 12th week, 5
      mg/kg/day isradipine (i.p) was given for 6 weeks. To the third group, the same
      dose of isradipine was given on the second day, followed by STZ treatment. The
      fourth group was non-diabetic and treated with 5 mg/kg/day isradipine for six
      weeks. The fifth group consisted of non-diabetic rats. To the sixth group,
      dexamethasone (5 mg/kg i.p.) was given to adult rats. For detection of apoptotic
      cells in paraffin-embedded thymus sections, the terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay
      was used. The DNA ladder method was performed for analysis of DNA fragmentation.
      In the isradipine-treated non-diabetic group, typical apoptotic banding patterns
      were found, whereas thick bands between 123 and 246 bp length were found in the n
      STZ- and n-STZ+isradipine-treated groups. More apoptotic cells were observed in
      the thymus of isradipine-treated, n-STZ-treated and n-STZ+isradipine-treated
      groups when compared with the non-diabetic control and isradipine+n-STZ-treated
      groups. In conclusion, we observed that long-term STZ diabetes results in
      apoptosis in the thymus. We also found that isradipine administered before STZ
      has protective effects against apoptosis, whereas isradipine alone induces
      apoptosis.

PMID- 15964615
TI  - Expression of integrin alpha5 and integrin beta4 and their extracellular ligands
      fibronectin and laminin in human decidua during early pregnancy and its sex
      steroid-mediated regulation.
AB  - The reorganization of the human endometrium is termed decidualization, which
      includes endometrial cell proliferation, differentiation, integrin switching and
      extracellular matrix (ECM) remodeling during early pregnancy. The present study
      aimed to investigate distribution patterns, staining intensity and sex steroid
      mediated regulation of integrin alpha5 (CD49e), integrin beta4 (CD49f) expression
      and their ligands fibronectin and laminin during decidualization. Human tissue
      samples were evaluated in two groups, those collected in early days and those
      collected in advanced days of the first trimester. Correlating immunostaining was
      found between laminin and integrin beta4, and between fibronectin and integrin
      alpha5. The expression of fibronectin was higher than that of laminin in the
      early days (p < 0.05). Temporal and spatial immunostaining of integrin beta4 and
      alpha5 in the apical pole of luminal and glandular cells was observed as
      pregnancy progressed (p < 0.05). In vitro results showed that human chorionic
      gonadotropin (hCG) stimulated laminin expression, downregulated integrin beta4
      expression, whereas estradiol decreased fibronectin expression by Ishikawa cells.
      hCG suppressed fibronectin expression in endometrial stromal cells in culture.
      Our results suggest that fibronectin is responsible for induction of decidual
      cell differentiation, and different temporal and spatial expression of the
      integrins may play a role in implantation. Our in vitro results suggest that
      regulation of extracellular matrix remodeling and integrin switching are at least
      partially regulated by reproductive hormones.

PMID- 15964616
TI  - Nicotine pretreatment diminished physostigmine-induced tremor in rats.
AB  - The aim of this work was evaluate the effects of acute and chronic nicotine
      pretreatment in the physostigmine-induced tremor in rats. Wistar male rats (3-4
      months) were pretreated acutely with different nicotine doses (0, 0.1, 0.5 or 1.0
      mg/kg) 10 min before physostigmine (0 and 0.5 mg/kg) treatment and then the
      tremor was registered by computerized system for 10 min. In another group, rats
      were pretreated acutely with 0.1 mg/kg of nicotine, recovered at different times
      (30 or 70 min), and were registered for physostigmine-induced tremor. Nicotine
      was also used chronically with equal doses for 8 days and recovered at 2, 7 or 21
      days before registration of physostigmine-induced tremor. Tremor spectral
      analysis was performed for amplitude and frequency quantification. Our data show
      that the acute and chronic nicotine pretreatments alter physostigmine spectrum
      profile. Nicotine decreased physostigmine-induced tremor amplitude (p<0.05),
      without changing its tremor frequency. In acutely pretreated rats, recovery
      experiments showed return of physostigmine-induced tremor for control levels
      after 70 min, but after 8 days of chronic nicotine pretreatment recovery was
      delayed 3 weeks. The data analysis shows that acute or chronic nicotine
      administration can alleviate the physostigmine-induced tremor. Chronic nicotine
      pretreatment has a long tremor alleviation effect of physostigmine-induced
      tremor. Possible mechanisms involving the nicotine effects on the physostigmine
      induced tremor are discussed.

PMID- 15964617
TI  - Oral administration of the 5-HT6 receptor antagonists SB-357134 and SB-399885
      improves memory formation in an autoshaping learning task.
AB  - In this work we aimed to re-examine the 5-HT6 receptor role, by testing the
      selective antagonists SB-357134 (1-30 mg/kg p.o.) and SB-399885 (1-30 mg/kg p.o.)
      during memory consolidation of conditioned responses (CR%), in an autoshaping
      Pavlovian/instrumental learning task. Bioavailability, half-life and minimum
      effective dose to induce inappetence for SB-357134 were 65%, 3.4 h, and 30 mg/kg
      p.o., and for SB-399885 were 52%, 2.2 h, and 50 mg/kg p.o., respectively. Oral
      acute and chronic administration of either SB-357134 or SB-399885 improved memory
      consolidation compared to control groups. Acute administration of SB-357134, at
      1, 3, 10 and 30 mg/kg, produced a CR% inverted-U curve, eliciting the latter dose
      a 7-fold increase relative to saline group. Acute injection of SB-399885 produced
      significant CR% increments, being 1 mg/kg the most effective dose. Repeated
      administration (7 days) of either SB-357134 (10 mg/kg) or SB-399885 (1 mg/kg)
      elicited the most significant CR% increments. Moreover, modeling the potential
      therapeutic benefits of 5-HT6 receptor blockade, acute or repeated administration
      of SB-399885, at 10 mg/kg reversed memory deficits produced by scopolamine or
      dizocilpine, and SB-357134 (3 and 10 mg/kg) prevented amnesia and even improved
      performance. These data support the notion that endogenously 5-HT acting, via 5
      HT6 receptor, improves memory consolidation.

PMID- 15964618
TI  - Embryo production from superovulated cattle following insemination of sexed
      sperm.
AB  - Two trials were conducted to ascertain fertilization rate, embryo quality and
      numbers of transferable embryos in superovulated heifers and cows inseminated
      with sexed sperm. Inseminates contained 2 x 10(6), 10 x 10(6) or 20 x 10(6) total
      sperm enriched for the X- or Y-chromosome ( approximately 90%) by flow
      cytometry/cell sorting. Non-sexed inseminates contained 40 x 10(6) total sperm.
      Donors in each trial were allocated to one of each of the bulls included in that
      study. Each donor was inseminated with frozen/thawed sperm from the same bull for
      each treatment in successive courses of superstimulation with twice daily i.m.
      injections of FSH for 4 d. Heifers and cows were inseminated 12 and 24 h after
      visually observed standing estrus in Trial 1. In Trial 2, a single timed
      inseminate was used 70-72 h following PGF(2alpha). Ova/embryos were collected non
      surgically 7-7.5 d after insemination. In both trials, fewer ova were fertilized
      with sexed versus non-sexed treatments and with 2 x 10(6) sexed sperm compared to
      higher doses (P < 0.05). However, insemination of 20 x 10(6) total sexed sperm of
      >or=90% purity resulted in similar numbers of transferable embryos of the desired
      sex compared to that for non-sexed sperm.

PMID- 15964619
TI  - Characteristics of rat round spermatids differentiated from spermatogonial cells
      during co-culture with Sertoli cells, assessed by flow cytometry,
      microinsemination and RT-PCR.
AB  - The present study was undertaken to investigate whether rat spermatogonial stem
      cells can differentiate into developmentally competent round spermatids during co
      culture with Sertoli cells. Type-A spermatogonia and Sertoli cells were prepared
      from 7-d-old Wistar-strain male rats, and seeded at 4 x 10(6) cells/ 4 mL/35-mm
      dish (Day 0). They were co-cultured at 37 degrees C for 3 d and at 34 degrees C
      for the subsequent 7d in 5% CO(2)/air. Round spermatid-like cells (approximately
      15 microm in diameter) were first observed on Day 5. A flow cytometric analysis
      showed that a single peak of haploid cells was detected in the cell populations
      harvested on Day 10. The participation of the spermatid-like cells to full-term
      development was examined by microinjection into activated oocytes. The oviductal
      transfer of 143 microinseminated oocytes resulted in only 8 implantation sites
      (6%), but no viable offspring. The expression of the round spermatid-specific
      marker gene, PRM-2, was confirmed in the Day 10 cell population by RT-PCR;
      however, no mRNA of two other haploid makers, TP1 or TP2, was detected. These
      results suggested that rat type-A spermatogonial cells underwent meiosis during
      the primary co-culture with the Sertoli cells, based on morphology, flow
      cytometry and PRM-2 expression, but the normality of the spermatid-like cells was
      not supported by microinsemination and TP1/2 expression.

PMID- 15964620
TI  - Technological issues for the development of more efficient calcium phosphate bone
      cements: a critical assessment.
AB  - The first calcium phosphate cements (CPCs) were discovered in the 1980s. Two
      decades later, the interest for these materials is still rising. The goal of the
      present document is to review the most recent achievements in the field and to
      analyze future directions in research and development.

PMID- 15964621
TI  - Solvent and water retention in dental adhesive blends after evaporation.
AB  - This study examined the extent of organic solvent and water retention in
      comonomer blends with different hydrophilicity (Hoy's solubility parameter for
      hydrogen bonding, delta(h)) after solvent evaporation, and the extent of tracer
      penetration in polymerised films prepared from these resins. For each comonomer
      blend, adhesive/solvent mixtures were prepared by addition of (1) 50 wt% acetone,
      (2) 50 wt% ethanol, (3) 30 wt% acetone and 20 wt% water and (4) 30 wt% ethanol
      and 20 wt% water. The mixtures were placed in glass wells and evaporated for 30
      60s for acetone-based resins, and 60-120 s for ethanol-based resins. The weight
      of the comonomer mixtures was measured before and after solvent evaporation.
      Resin films were prepared for transmission electron microscopy (TEM) after
      immersion in ammonical silver nitrate. The percentages of solvent and water
      retained in the comonomer mixtures, and between the acetone and ethanol groups
      were measured gravimetrically and were statistically compared. In comonomer
      organic solvent mixtures, the percentage of solvent retained in acetone and
      ethanol-based mixtures increased significantly with hydrophilicity of the
      comonomer blends (P < 0.05). In resin-organic solvent-water mixtures,
      significantly more solvent and water were retained in the ethanol-based mixtures
      (P < 0.0001), when compared to acetone-based mixtures after 60s of air-drying.
      TEM revealed residual water being trapped as droplets in resin films containing
      acetone and water. Water-filled channels were seen along the film periphery of
      all groups and throughout the entire resin films containing ethanol and water.
      The addition of water to comonomer-ethanol mixtures results in increased
      retention of both ethanol and water because both solvents can hydrogen bond to
      the monomers.

PMID- 15964622
TI  - Aqueous dispersions of magnetite nanoparticles with NH3+ surfaces for magnetic
      manipulations of biomolecules and MRI contrast agents.
AB  - In the current study, amine surface modified iron-oxide nanoparticles of 6 nm
      diameter without polymer coating were fabricated in an aqueous solution by
      organic acid modification as an adherent following chemical coprecipitation.
      Structure and the superparamagnetic property of magnetite nanoparticles were
      characterized by selected area electron diffraction (SAED) and superconducting
      quantum interference measurement device (SQUID). X-ray photoelectron spectrometer
      (XPS) and zeta potential measurements revealed cationic surface mostly decorated
      with terminal -NH(3)(+). This feature enables them to function as a magnetic
      carrier for nucleotides via electrostatic interaction. In addition,
      Fe(3)O(4)/trypsin conjugates with well-preserved functional activity was
      demonstrated. The nanoparticles displayed excellent in vitro biocompatibility.
      The NMR and the in vitro MRI measurements showed significantly reduced water
      proton relaxation times of both T(1) and T(2). Significantly reduced T(2) and
      T(2)*-weighted signal intensity were observed in a 1.5 T clinical MR imager. In
      vivo imaging contrast effect showed a fast and prolonged inverse contrast effect
      in the liver that lasted for more than 1 week. In addition, it was found that the
      spherical Fe(3)O(4) assembled as rod-like configuration through an aging process
      in aqueous solution at room temperature. Interestingly, TEM observation of the
      liver tissue revealed the rod-like shape but not the spherical-type nanoparticles
      being taken up by the Kupffer cells 120 h after tail vein infusion. Combining
      these results, we have demonstrated the potential applications of the newly
      synthesized magnetite nanoparticles in a broad spectrum of biomedical
      applications.

PMID- 15964623
TI  - Implantation of preadipocyte-loaded hyaluronic acid-based scaffolds into nude
      mice to evaluate potential for soft tissue engineering.
AB  - The reconstruction of soft tissue defects following extensive deep burns or tumor
      resections remains an unresolved problem in plastic and reconstructive surgery
      since adequate implant materials are still not available. Preadipocytes, immature
      precursor cells found between mature adipocytes in adipose tissue, are a
      potential material for soft tissue engineering since they can proliferate and
      differentiate into adipose tissue after transplantation. In previous studies, we
      identified hyaluronan benzyl ester (HYAFF 11) sponges to be promising carrier
      matrices. This study now evaluates, in vitro and in vivo, a new sponge
      architecture with pores of 400 microm either made of plain HYAFF 11 or HYAFF 11
      coated with the extracellular matrix glycosaminoglycan hyaluronic acid. Human
      preadipocytes were isolated, seeded onto carriers and implanted into nude athymic
      mice. Explants harvested after 3, 8, and 12 weeks were examined for macroscopical
      appearance, thickness, weight, pore structure, histology, and
      immunohistochemistry. Compared to previous studies, we found better penetration
      of cells into both types of scaffolds, with more extensive formation of new
      vessels throughout the construct but with only minor adipose tissue. Our
      encouraging results contribute towards a better seeded and vascularised scaffold
      but also show that the enhancement of adipogenic conversion of preadipocytes
      remains a major task for further in vivo experiments.

PMID- 15964624
TI  - In vitro evaluation of low-intensity pulsed ultrasound in herniated disc
      resorption.
AB  - Herniated disc (HD) is often resolved spontaneously without surgical
      intervention. HD resorption (HDR) is associated with abundant vascularization and
      infiltration of macrophages (Mphi) into the intervertebral disc (ID), as well as
      with high levels of matrix metalloproteinases (MMPs). Low-intensity pulsed
      ultrasound (LIPUS) accelerates bone fracture healing in clinical studies, and
      angiogenic factors are involved in the mechanism of action. In the present study,
      we examined the effects of LIPUS on HDR in a rat in vitro HD model. HDR was
      enhanced by LIPUS as measured by the change in the wet weight of the cultured ID.
      The secretion of tumor necrosis factor-alpha (TNF-alpha) and macrophage
      chemoattractant protein-1 (MCP-1) from Mphi into the culture medium was
      stimulated by LIPUS. LIPUS also enhanced matrix metalloproteinase-3 (MMP-3)
      maturation. Moreover, many apoptotic cell death were observed in the HDR groups
      with LIPUS exposure. These results suggest that LIPUS enhanced the HDR via MMP-3
      activation through TNF-alpha and MCP-1 pathways. Although animal studies and
      clinical trial are needed to understand the LIPUS effects on HDR, LIPUS treatment
      might be an effective treatment for accelerating HDR.

PMID- 15964625
TI  - Negative regulation of p53 by nucleophosmin antagonizes stress-induced apoptosis
      in human normal and malignant hematopoietic cells.
AB  - Nucleophosmin (NPM) is a multifunctional protein frequently overexpressed in
      actively proliferating cells including tumor and stem cells. Here we show that
      NPM acts as a cellular p53 negative regulator to protect normal and malignant
      hematopoietic cells from stress-induced apoptosis. Overexpression of NPM
      suppresses stress-induced apoptosis in the granulocyte-macrophage colony
      stimulating factor (GM-CSF)-dependent myeloid cell line MO7e and the lymphoblast
      HSC536 cells derived from a Fanconi anemia (FA) patient. In addition, suppression
      of NPM expression by small interfering RNA targeting NPM in normal lymphoblasts
      and FA-associated acute myelogenous leukemia (AML) cells increases DNA damage
      induced apoptosis. However, overexpression of the mutant NPMDeltaC, which lacks
      the p53-interacting domain, fails to confer cellular resistance to stress-induced
      apoptosis, suggesting that NPM protects cells from apoptotic cell death through a
      mechanism involving p53. Indeed, using the genetically matched p53 wild-type (WT)
      and null mouse bone marrow (BM) cells, we demonstrate that forced expression of
      NPM protects against ionizing irradiation (IR)-induced apoptosis of WT but not
      p53-null BM cells. Moreover, NPM inhibits IR-induced p53 transactivation, and
      interacts with p53 in hematopoietic cells. Thus, these results indicate an
      important role for NPM in regulation of p53-dependent apoptotic response and
      implicate a potential effect in cancer therapy.

PMID- 15964626
TI  - Evidence of a mechanism by which etanercept increased TNF-alpha in multiple
      myeloma: new insights into the biology of TNF-alpha giving new treatment
      opportunities--the role of bupropion.
AB  - Etanercept is a commercially available pharmaceutical protein approved for
      treatment of rheumatoid arthritis, RA. Given subcutaneously, etanercept binds and
      inactivates soluble tumor necrosis factor-alpha, TNF. Etanercept has a good
      safety record and is of benefit in lowering pain, inflammation, and joint
      destruction in RA. RA is mediated by many factors, TNF among them. Malignant
      myeloma, MM, is a malignant clonal expansion of a post-germinal center B
      lymphocyte. Since TNF is a necessary growth factor for expansion and maintenance
      of MM cells, and etanercept binds soluble TNF and is of clinical benefit in RA,
      etanercept was tried experimentally in MM. Contrary to expectations, etanercept
      resulted in increased levels of TNF and possibly shortened survival. This paper
      presents an hypothesis of how this happened. There are two cognate receptors for
      TNF, termed R1 and R2 and two forms of TNF, soluble and transmembrane. Soluble
      TNF has greater affinity for TNF-R1 than for TNF-R2. Transmembrane TNF has equal
      affinity for the two receptors. Since TNF-R2 signaling tends to be more anti
      apoptotic and activating of nuclear factor kappa B, NFkB, than is TNF-R1, and TNF
      R1 tends to be more pro-apoptotic than is TNF-R2, by inactivating soluble TNF
      while leaving transmembrane TNF signaling relatively unchanged, etanercept
      changed the balance in TNF signaling from TNF-R1 towards TNF-R2 weighting. Anti
      apoptosis and TNF synthesis would have been up-regulated by that shift. Early
      data indicates that the common generic antidepressant bupropion may ameliorate
      Crohn's disease course by down regulating TNF synthesis, maybe it will slow the
      course of MM as well.

PMID- 15964627
TI  - Sequence analysis of the plasmid genome of the probiotic strain Lactobacillus
      paracasei NFBC338 which includes the plasmids pCD01 and pCD02.
AB  - Lactobacillus paracasei NFBC338 is a probiotic strain that was isolated from the
      human gastrointestinal tract (GIT) and contains a plasmid genome of 80kb. Using a
      shotgun sequencing approach, two of the plasmids, pCD01 (19,882bp) and pCD02
      (8554bp) have been completely sequenced, and four contiguous sequences (Contigs)
      have been assembled. Bioinformatic analysis of pCD01 revealed that it contains 23
      putative open reading frames (ORFs) and that it contains regions characterised by
      potential replication functions and multidrug resistance (MDR). In contrast, the
      content of pCD02 is mainly cryptic, although, it does contain two insertion
      sequence (IS) elements. Indeed, up to 17% of the entire plasmid genome encodes
      putative transposable elements. In addition, there are a number of interesting
      ORFs distributed over the four Contigs that show significant homology to genes
      such as those involved in adherence and biotin metabolism, which may prove
      beneficial to Lb. paracasei NFBC338 under certain environmental conditions. This
      study provides a novel insight into the rich plasmid complement of this probiotic
      Lactobacillus strain, which may potentially be exploited as the basis for
      development of improved genetic tools for probiotic lactobacilli.

PMID- 15964628
TI  - Gill and liver histopathological changes in yellow perch (Perca flavescens) and
      goldfish (Carassius auratus) exposed to oil sands process-affected water.
AB  - The extraction of bitumen from the Athabasca oil sands (Alberta, Canada) produces
      significant volumes of process-affected water containing elevated levels of
      naphthenic acids (NAs), ions, and polycyclic aromatic hydrocarbons (PAHs). The
      sublethal response of aquatic organisms exposed to oil sands constituents in
      experimental aquatic environments that represent possible reclamation options has
      been studied. In this study, the effects of process-affected waters on gill and
      liver tissues in yellow perch (Perca flavescens) and caged goldfish (Carassius
      auratus) held in several reclamation ponds at Syncrude's Mildred Lake site have
      been assessed. Following a 3-week exposure, significant gill (epithelial cell
      necrosis, mucous cell proliferation) and liver (hepatocellular degeneration,
      inflammatory cell infiltration) histopathological changes were noted in fish held
      in waters containing high levels of oil sands process-affected water. In
      addition, measurements of gill dimensions (gill morphometrical indices) proved
      sensitive and provided evidence of a physiological disturbance (gas exchange)
      with exposure to oil sands materials. Due to the complexity of oil sands process
      affected water, the cause of the alterations could not be attributed to specific
      oil sands constituents. However, the histopathological parameters were strong
      indicators of exposure to oil sands process-affected water and morphometrical
      data were sensitive indicators of pathological response, which can be used to
      identify the interactive effects of ionic content, NAs, and PAHs in future
      laboratory studies.

PMID- 15964629
TI  - A review of botanical phytochemicals with mosquitocidal potential.
AB  - Identification of novel effective mosquitocidal compounds is essential to combat
      increasing resistance rates, concern for the environment and food safety, the
      unacceptability of many organophosphates and organochlorines and the high cost of
      synthetic pyrethroids. An increasing number of researchers are reconsidering
      botanicals containing active phytochemicals in their efforts to address some of
      these problems. To be highly competitive and effective, the ideal phytochemical
      should possess a combination of toxic effects and residual capacity. Acute
      toxicity is required at doses comparable to some commercial synthetic
      insecticides while chronic or sub-chronic toxicity is required to produce growth
      inhibition, developmental toxicity and generational effects. In this article, we
      review the current state of knowledge on larvicidal plant species, extraction
      processes, growth and reproduction inhibiting phytochemicals, botanical ovicides,
      synergistic, additive and antagonistic joint action effects of mixtures, residual
      capacity, effects on non-target organisms, resistance, screening methodologies,
      and discuss promising advances made in phytochemical research.

PMID- 15964630
TI  - Cataract surgery in relative anterior microphthalmos.
AB  - PURPOSE: To determine the prevalence of relative anterior microphthalmos (RAM)
      and evaluate intraoperative performance and surgical outcome in eyes with RAM
      undergoing cataract surgery. DESIGN: Nested case-control series. PARTICIPANTS:
      One thousand four hundred consecutive patients undergoing cataract surgery were
      evaluated to determine the prevalence of RAM. Relative anterior microphthalmos is
      defined as horizontal corneal diameter (HCD) < or =11 mm, anterior chamber depth
      (ACD) < or =2.2 mm, and axial length (AL) >20 mm, with no other morphologic
      malformation. METHODS: Patients were examined preoperatively for HCD, ACD, and
      AL. Horizontal corneal diameter was measured with calipers. Anterior chamber
      depth and AL were measured with immersion shell with water. Associated ocular
      pathologic conditions were recorded. Two control groups were identified. Group I
      (normal eyes; n = 84) had HCD >11 mm, ACD >2.2 mm, and AL >20 mm. Group II (eyes
      with small corneal diameter; n = 84) had HCD < or =11 mm, ACD >2.2 mm, and AL >20
      mm. MAIN OUTCOME MEASURES: Patients with RAM and controls were evaluated for
      intraoperative performance and postoperative outcome. The 2-tailed Fisher exact
      test was applied to compare the performance of RAM with each of the control
      groups. The odds ratio (OR) with 95% confidence intervals (95% CI) was
      determined. RESULTS: The prevalence of RAM was 6% (84 of 1400 eyes; 95%CI, 0.048
      0.074). Relative anterior microphthalmos was associated with the presence of
      small pupil, 34 (40.48%); corneal guttae, 31 (36.9%); glaucoma, 29 (34.5%); and
      pseudoexfoliation, 6 (7.14%). Intraoperatively, RAM was associated with overall
      surgical difficulty because of less working space in 59 eyes (70.24%; OR, 63.7;
      95% CI, 18.3-221; P<0.001) compared with control groups I and II; uveal trauma in
      12 (14.28%); Descemet's detachment in 5 (5.95%); and posterior capsule rupture in
      2 (2.38%). Postoperatively, RAM was associated with transient corneal edema in 63
      eyes (75%; OR, 9.0; 95% CI, 4.4-18.0; P<0.001; OR, 5.4; 95% CI, 2.7-10.5;
      P<0.001) on the first postoperative day. CONCLUSIONS: The prevalence of RAM was
      6%. Relative anterior microphthalmos with its associations posed significant
      intraoperative difficulties. The occurrence of transient corneal edema was
      frequent.

PMID- 15964631
TI  - Corneal thickness in an ophthalmologically normal Japanese population.
AB  - PURPOSE: To investigate the distribution of central corneal thickness (CCT) and
      factors correlating with CCT in a large-scale population of ophthalmologically
      normal Japanese persons. DESIGN: Cross-sectional study. PARTICIPANTS:
      Participants (n = 7313; 2848 men and 4465 women) were selected as an
      ophthalmologically normal Japanese sample using the following exclusion criteria:
      abnormal results suggestive of any eye diseases revealed on slit-lamp
      examination, fundus photography, or visual field test using frequency doubling
      technology; corrected visual acuity worse than 0.7; and contact lens wear within
      1 week. All study participants were identified from The Eye Disease Screening
      Service in Tajimi city during the period from September, 2000, through October,
      2001. METHODS: The CCT was measured by SP-2000P specular microscopy (Topcon,
      Tokyo, Japan). Age, gender, body mass index, systolic blood pressure, laterality,
      refraction, corneal radius, and intraocular pressure (IOP) data were collected
      from the records. MAIN OUTCOME MEASURES: The CCT value and its correlating
      factors. RESULTS: Average CCT in this ophthalmologically normal Japanese
      population was 517.5+/-29.8 microm (mean+/-standard deviation; n = 7313) and was
      greater in men (521.5+/-30.3 microm) than in women (514.4+/-29.0 microm). The CCT
      positively correlated with IOP and corneal radius and negatively correlated with
      refraction, although the correlation was weak. Intraocular pressure measured with
      a Goldmann applanation tonometer positively correlated with CCT, and the
      correction was not affected by age (corrected IOP = IOP reading -0.012 [CCT
      (microm) - 520]). CONCLUSIONS: Using optical pachymetry, CCT in normal Japanese
      persons was defined as 517.5+/-29.8 microm. Men had greater CCT measurements than
      women. The CCT measurements positively correlated with IOP and corneal radius and
      negatively correlated with age and refraction in men. Intraocular pressure
      positively correlated with CCT, regardless of age.

PMID- 15964632
TI  - Gamma-Diketone central neuropathy: quantitative analyses of cytoskeletal
      components in myelinated axons of the rat rubrospinal tract.
AB  - Loss of axon caliber is a primary component of gamma-diketone neuropathy
      [LoPachin RM, DeCaprio AP. gamma-Diketone central neuropathy: axon atrophy and
      the role of cytoskeletal protein adduction. Toxicol Appl Pharmacol 2004;199:20
      34]. It is possible that this effect is mediated by changes in the density of
      cytoskeletal components and corresponding spatial relationships. To examine this
      possibility, morphometric methods were used to quantify the effects of 2,5
      hexanedione (HD) intoxication on neurofilament-microtubule densities and nearest
      neighbor distances in myelinated rubrospinal axons. Rats were exposed to HD at
      one of two daily dose-rates (175 or 400 mg/kg per day, gavage) until a moderate
      level of neurotoxicity was achieved (99 or 21 days of intoxication, respectively)
      as determined by gait analysis and measurements of hindlimb grip strength.
      Results indicate that, regardless of dose-rate, HD intoxication did not cause
      changes in axonal neurofilament (NF) density, but did significantly increase
      microtubule (MT) density. No consistent alterations in interneurofilament or NF
      MT distances were detected by ultrastructural morphometric analyses. These data
      suggest that the axon atrophy induced by HD was not mediated by major disruptions
      of stationary cytoskeletal organization. Recent biochemical studies of spinal
      cord from HD intoxicated rats showed that, although the NF protein content in the
      stationary cytoskeleton (polymer fraction) was not affected, the mobile subunit
      pool was depleted substantially [LoPachin RM, He D, Reid ML, Opanashuk LA. 2,5
      Hexanedione-induced changes in the monomeric neurofilament protein content of rat
      spinal cord fractions. Toxicol Appl Pharmacol 2004;198:61-73]. The stability of
      the polymer fraction during HD intoxication is consistent with the absence of
      significant ultrastructural modifications noted in the present study. Together,
      these findings implicate loss of mobile NF proteins as the primary mechanism of
      axon atrophy.

PMID- 15964633
TI  - Synthesis, characterization and antiproliferative behavior of tricarbonyl
      complexes of rhenium(I) with some 6-amino-5-nitrosouracil derivatives: crystal
      structure of fac-[ReCl(CO)3(DANU-N5,O4)] (DANU=6-amino-1,3-dimethyl-5
      nitrosouracil).
AB  - New complexes of rhenium(I) with some 5-nitrosopyrimidines with general formula
      [ReCl(CO)3L] have been prepared and characterized by elemental analysis,
      conductivity measurements, IR and 1H, 13C and 15N NMR spectroscopic methods. The
      complexes appear to be monomeric and the pyrimidine ligands act in a neutral
      form. The structure of [ReCl(CO)3(DANU)].CH3CN has been solved by X-ray
      diffraction. The coordination environment around the Re(I) may be described as a
      distorted octahedron in which the ligand behaves in a bidentate fashion through
      N5 and O4 atoms, making a five-membered chelate ring. The coordination sphere is
      completed with three carbonyl groups in fac-arrangement and one chlorine atom.
      The evaluation of the antiproliferative behavior against five human tumor cell
      lines (human breast cancer MCF-7 and EVSA-T, human neuroblastoma NB69, human
      glioma H4 and human bladder carcinoma cell line ECV) suggested a modulator
      behavior of cell growth at low concentrations due to their estrogenic-like
      characteristics.

PMID- 15964634
TI  - Speciation study of an imidazolate-bridged copper(II)-zinc(II) complex in aqueous
      solution.
AB  - The solution equilibrium and the binding mode of the species in the five
      component system containing two metal ions (copper(II) and zinc(II)) and three
      ligands (A=diethylenetriamine, B=imidazole, C=tris(2-aminoethyl)amine) were
      investigated by pH-potentiometric titration, UV-visible spectrophotometry and EPR
      (electron paramagnetic resonance) spectroscopic titration in aqueous solution in
      the 2-11 pH range. An imidazolate-bridged heterobinuclear complex (ACuBH(-1)ZnC)
      was found to evolve above pH=7 and was stable between pH 7 and 11. The existence
      of the ACuBH(-1)ZnC complex (by determination of its molecular weight) was proved
      by mass spectrometry (ESI-MS (electrospray ionization mass spectrometry) and
      MALDI (matrix-assisted laser desorption/ionization) techniques). The
      electrochemical behaviour and the superoxide dismutase activity of this complex
      were also tested by cyclic voltammetry and the Riboflavin/NBT (nitro blue
      tetrazolium) assay, respectively.

PMID- 15964635
TI  - Gene expression microarray studies in polygenic psychiatric disorders:
      applications and data analysis.
AB  - Gene expression microarrays have become a mainstream technology that can provide
      valuable insight into psychiatric disorders. Gene expression studies in post
      mortem brain samples of schizophrenia and bipolar disorder have the potential to
      yield novel clues about the pathophysiology of these complex trait disorders. In
      the present review, a short introduction of the genetic and molecular background
      of schizophrenia and bipolar disorder is followed by a discussion of the basic
      concept and limits of gene expression microarray technology, and the complexities
      surrounding the analysis of thousands of gene transcripts. Although this review
      is intended for use in most platforms, it has a particular focus on the
      commercially available Affymetrix system. Various computer programs and their
      principal features are discussed, and it is shown how these programs can be
      applied to reveal a biological context of microarray findings. I will demonstrate
      how the programs can help to judge the results rather than focus on their
      statistical principles. The strength of gene array experiments is their emphasis
      on broad, biological themes, rather than on specific genes, and proper
      biostatistical approaches are important to ensure reproducibility of the
      findings. All results should be verified by independent means. This review is
      intended to help brain researchers who want to apply gene expression microarray
      technology to conceptualize research strategies and sample analysis.

PMID- 15964636
TI  - Sterile wounding is a minimal and sufficient trigger for a cellular immune
      response in Drosophila melanogaster.
AB  - An attack and oviposition by parasitic wasp Leptopilina boulardi induces a
      vigorous cellular immune response in Drosophila melanogaster larvae. This
      response is manifested by the appearance of a specialized subset of blood cells,
      the lamellocytes, which are the key players in the encapsulation and killing of
      the parasite. The formation of lamellocytes involves the activation of the Toll,
      the Jun kinase and the JAK/STAT pathways however the minimal requirement for
      initiation of lamellocyte development in the course of the cellular immune
      response has not been defined yet. In this study, we tested whether or not the
      mechanical injury itself, caused by oviposition, could provide a sufficient
      signal for lamellocyte development. We found that sterile wounding, comparable to
      that occurring during oviposition, induces normal lamellocyte development. We
      propose therefore that mechanical damage of the cuticle and subsequent disruption
      of the basal lamina is a minimal and sufficient single signal for normal
      lamellocyte development in the course of the cellular immune response of
      Drosophila.

PMID- 15964637
TI  - Proteasome antibodies in paraneoplastic cerebellar degeneration.
AB  - Antibodies to proteasome have been detected in several autoimmune diseases,
      including multiple sclerosis. We have investigated the presence of such
      antibodies in patients with paraneoplastic neurological syndromes, by Western
      blotting and immunohistochemistry. Antibodies to 20S proteasome were detected in
      the majority of patients with paraneoplastic cerebellar degeneration (PCD), but
      in only one of nine sera from patients with paraneoplastic
      encephalomyelitis/sensory neuronopathy (PEM/SN), and were not found in cancer
      patients in general. The results suggest that the immune responses in PCD differ
      from those of PEM/SN, whereas the functional significance of proteasome
      antibodies in PCD is yet to be determined.

PMID- 15964638
TI  - Immune pre-activation exacerbates hemorrhagic brain injury in immature mouse
      brain.
AB  - Premature infants with placental infection and adult stroke patients with fever
      have worse outcomes following intracerebral hemorrhage (ICH). We hypothesized
      that immune pre-activation would aggravate brain injury in mouse brain following
      ICH. The immune system of 2-day, 10-day and 7-week young adult CD1 mice was
      stimulated by intraperitoneal injection of concanavalin A (ConA),
      lipopolysaccharide (LPS) or polyinosinic-polycytidilic acid (PolyI:C) 12 h prior
      to intracerebral injection of blood. Two days later, brain damage and
      inflammation were worse in 2-day mice that had received LPS. The other agents had
      less consistent effects in 2-day mice. Brain damage in young adults was
      aggravated less after immune stimulation. These data suggest that immune pre
      activation modifies hemorrhagic brain injury in immature mouse brain.

PMID- 15964639
TI  - Electronystagmography finding in children with peripheral and central vestibular
      disorders.
AB  - OBJECTIVE: Dizziness and imbalance are uncommon in children, but often alarming
      for their families: a detailed interview and otoneurological examination are
      important for reaching a specific diagnosis and treatment. Children with
      vestibular disorders are thought to be difficult to examine: vestibular tests
      (caloric test, roto-acceleratory test, electronystagmography, opto-kinetic
      nystagmus, cranio-corpography and posturography) are used less frequently for
      children than in adult patients. The aim of the study was to determine whether
      the results of electronystagmography testing improve an emergency physician's
      diagnosis of dizziness in children. METHODS: Patients were selected on the basis
      of the following inclusion criteria: aged between 2 and 12 years and affected
      with vertiginous symptoms. All patients underwent the following instrumental
      examinations: blood tests, audiological screening, electronystagmography of
      spontaneous nystagmus or provoked by vestibular and optical stimulation and
      electroencephalogram. RESULTS: The results underlines an high incidence of
      central vertigo (83%): 52% of the children presented a prevailing unidirectional
      nystagmus at labyrinth stimulation and 48% of the children an asymmetry in the
      response of nystagmus at optical kinetic stimulation with quality alteration of
      shocks. CONCLUSIONS: Electronystagmography can register and evaluate the
      qualitative and quantitative characteristics of the nystagmic response and allow
      to distinguish between central or peripheric vertigo: different degrees and
      various combinations of the abnormal responses shown in optokinetic central test
      were the most characteristic of electronystagmography in patients with vestibular
      central vertigo.

PMID- 15964640
TI  - Real-time assay for quantitative detection of non-persistently transmitted Plum
      pox virus RNA targets in single aphids.
AB  - A TaqMan real-time RT-PCR was developed to detect and quantify RNA-targets from
      the non-circulative, non-persistently transmitted Plum pox virus (PPV) in
      individual fresh or aphids captured previously and squashed on paper. Reliable
      quantitation ranged from 40 up to 4 x 10(8) copies of control transcripts. This
      technique was applied successfully to plant material and to individual PPV vector
      (Myzus persicae) and non-vector of PPV (Aphis nerii) aphid species demonstrating
      acquisition of viral targets by both vector and non-vector aphids. The number of
      viruliferous aphids detected by real-time RT-PCR and nested RT-PCR in a single
      closed tube was similar in parallel assays, nevertheless the sensitivity provided
      by real-time RT-PCR was 100 times higher than nested RT-PCR and 1000 times higher
      than DASI-ELISA and conventional RT-PCR. The quantities of PPV-RNA targets
      detected in a single aphid ranged from 40 to more than 2 x 10(3) units. The
      combined system (immobilization of targets on paper by squash capture and real
      time RT-PCR) allows, for the first time, reliable quantitation of PPV targets
      acquired by individual aphid species and constitute an excellent tool for
      understanding better PPV epidemiology.

PMID- 15964641
TI  - Overeating of palatable food is associated with blunted leptin and ghrelin
      responses.
AB  - Palatable food is rich in fat and/or sucrose. In this study we examined the long
      term effects of such diets on food intake, body weight, adiposity and circulating
      levels of the satiety peptide leptin and the hunger peptide ghrelin. The
      experiments involved rats and mice and lasted 5 weeks. In rats, we examined the
      effect of diets rich in fat and/or sucrose and in mice the effect of a high fat
      diet with or without sucrose in the drinking water. Animals fed with the
      palatable diets had a larger intake of calories, gained more weight and became
      more adipose than animals fed standard rat chow. Fasted animals are known to have
      low serum leptin and high serum ghrelin and to display elevated serum leptin and
      lowered serum ghrelin postprandially. With time, a sucrose-rich diet was found to
      raise the fasting level of leptin and to lower the fasting level of ghrelin in
      rats. A fat-rich diet suppressed serum ghrelin without affecting serum leptin;
      high sucrose and high fat in combination greatly reduced serum ghrelin and raised
      serum leptin in the fasted state. The mRNA expression of leptin in the rat
      stomach was up-regulated by sucrose-rich (but not by fat-rich) diets, whereas the
      expression of ghrelin seemed not to be affected by the palatable diets. Mice
      responded to sucrose in the drinking water with elevated serum leptin (fasted
      state) and to all palatable diets with low serum ghrelin. The expression of both
      leptin and ghrelin mRNA in the stomach was suppressed in fasted mice that had
      received a high fat diet for 5 weeks. We conclude that the expression of leptin
      mRNA in stomach and the concentration of leptin in serum were elevated in
      response to sucrose-rich rather than fat-rich diets, linking leptin with sucrose
      metabolism. In contrast, the expression of ghrelin and the serum ghrelin
      concentration were suppressed by all palatable diets, sucrose and fat alike. In
      view of the increased body weight and adiposity neither elevated leptin nor
      suppressed ghrelin were able to control/restrain the overeating that is
      associated with palatable diets.

PMID- 15964642
TI  - Catheter ablation for atrial fibrillation: The Chinese experience.

PMID- 15964643
TI  - High-sensitivity C-reactive protein is predictive of successful cardioversion for
      atrial fibrillation and maintenance of sinus rhythm after conversion.
AB  - BACKGROUND: Cardioversion for atrial fibrillation (AF) is the most effective
      treatment for the restoration of sinus rhythm (SR). Recently, an elevated level
      of hs-CRP has been shown to be associated with AF burden, suggesting that
      inflammation increases the propensity for persistence of AF. We examined whether
      the level of high-sensitivity C-reactive protein (hs-CRP) was predictive of the
      outcome of cardioversion for AF. METHODS AND RESULTS: One hundred and six
      patients with a history of symptomatic AF lasting > or =1 day (age 63+/-14 years,
      mean+/-S.D.) underwent cardioversion. Echocardiography and hs-CRP assay were
      performed immediately prior to cardioversion. SR was restored in 84 patients
      (79%). By using selected cutoff values, multiple discriminant analysis revealed
      significant associations between successful cardioversion and a shorter duration
      of AF (AF duration< or =36 days, odds ratio (OR), 0.98; 95% confidence interval
      (CI), 0.97-0.99), smaller left atrial diameter (left atrial diameter< or =40 mm,
      OR 0.82, 95% CI 0.71-0.94), better-preserved left ventricular ejection fraction
      (left ventricular ejection fraction> or =60%, OR 0.92, 95% CI 0.86-0.99), and
      lower hs-CRP level (hs-CRP< or =0.12 mg/dL, OR 0.33, 95% CI 0.21-0.51). During a
      follow-up period of 140+/-144 days, AF recurred in 64 patients (76%). By using a
      cutoff value of hs-CRP> or =0.06 mg/dL, Cox proportional-hazards regression model
      found that only hs-CRP level was an independent predictor of AF recurrence (OR
      5.30, 95% CI 2.46-11.5) after adjustment for coexisting cardiovascular risks.
      When patients were divided by the hs-CRP level of 0.06 mg/dL, percentage of
      maintenance of SR below and above the cutoff was 53% and 4%, respectively (log
      rank test, p<0.0001). CONCLUSIONS: hs-CRP level determined prior to cardioversion
      represents an independent predictor of both successful cardioversion for AF and
      the maintenance of SR after conversion.

PMID- 15964644
TI  - The diagnostic value of troponin T testing in the community setting.
AB  - BACKGROUND: Many patients presenting with chest pain to their family physician
      are referred to the emergency room, in part, due to lack of accurate objective
      diagnostic tools. This study aimed to assess the diagnostic value of bedside
      troponin T kit testing in patients presenting with chest pain to their family
      physician. DESIGN: Prospective, multi-center study. METHODS: Consecutive subjects
      with chest pain were recruited from 44 community clinics in Jerusalem. Following
      clinical assessment by the family physician, qualitative troponin kit testing was
      performed. Patients with a negative clinical assessment and negative troponin kit
      were sent home and all others were referred to the emergency room. The final
      diagnosis at the time of hospital discharge was recorded and telephone follow up
      was performed after 60 days. Positive predictive value, negative predictive
      value, sensitivity and specificity of troponin kit for myocardial infarction
      diagnosis and of family physician for hospitalization, were assessed. RESULTS: Of
      392 patients enrolled, 349 (89%) were included in the final analysis. The
      prevalence of myocardial infarction was 1.7%. The positive and negative
      predictive values of the troponin kit for myocardial infarction diagnosis were
      100% and 99.7%, respectively. The positive and negative predictive values of the
      family physician's assessment to predict hospitalization were 41.4% and 94.1%,
      respectively. CONCLUSIONS: Troponin kit testing is an important tool to assist
      the family physician in the assessment of patients with chest pain in the
      community setting. Troponin kit testing may identify otherwise undiagnosed cases
      of myocardial infarctions, and reduce unnecessary referrals to the emergency
      room.

PMID- 15964645
TI  - Triggering activities of acute pulmonary embolism and paradoxical embolism.

PMID- 15964646
TI  - Management of small bowel interferences in primary radiotherapy of prostate
      cancer.

PMID- 15964647
TI  - Bi-phasic hitting with constraints on impact velocity and temporal precision.
AB  - The aim of the experiment was to investigate how bi-phasic hitting movements are
      organized to comply with both impact and temporal precision constraints. 'Bi
      phasic' refers to a sequential movement with a preparatory movement away from the
      interception location followed by a strike phase. The interception location was
      fixed, as the motion of the hitting device was constrained to follow a straight
      path orthogonal to that of the approaching balls. We manipulated the required
      temporal precision by projecting balls with different constant approach speeds
      (1, 1.5, and 2m/s). Different impact constraints were imposed by instructing
      participants first to simply hit the ball and subsequently to hit the ball to a
      designated target area located either 55 or 105 cm away from the interception
      location. We determined several kinematic variables and used Principal Component
      Factor Analysis to classify these variables. The analysis revealed two
      independent factors: a 'velocity' factor (formed by impact velocity, peak
      velocity of the preparatory phase, peak velocity of the strike phase, and
      amplitude of the strike) and a 'timing' factor (formed by onset of the
      preparatory phase, moment of peak velocity of the preparatory phase, and onset of
      the strike phase). The 'velocity' factor scaled significantly with the required
      impact constraint and the 'timing' factor scaled significantly with ball speed.

PMID- 15964648
TI  - Arm coordination symmetry and breathing effect in front crawl.
AB  - This study analysed the relationships among arm coordination symmetry, motor
      laterality and breathing laterality during a 100-m front crawl, as a function of
      expertise. Ten elite swimmers (G1), 10 mid-level swimmers (G2), and 8 non-expert
      swimmers (G3) composed three skill groups, which were distinguished by velocity,
      stroke rate, stroke length, breathing frequency (BF) and the mean number of
      strokes between two breaths - the stroke breath (SB) - over a 100-m front crawl.
      Four stroke phases were identified by video analysis (catch, pull, push and
      recovery) and the index of coordination (IdC) measured the lag time between the
      propulsive phases of the two arms. The three modes of coordination are catch-up
      (IdC<0%), opposition (IdC=0%) and superposition (IdC>0%). The IdC was established
      as the mean of IdC1 and IdC2, which measured the lag time between the propulsive
      phases of the left and right arms, respectively. The coordination symmetry was
      analysed by comparing IdC1 and IdC2, and the breathing effect was studied by
      distinguishing IdC1 (and IdC2) with and without breathing. Motor laterality was
      determined by an adaptation of the Edinburgh Handedness Inventory. Breathing
      laterality was determined by a questionnaire and observation during the 100-m
      trial. Most of the front crawl swimmers showed asymmetric arm coordination, with
      propulsive discontinuity on one side and propulsive superposition on the other.
      This asymmetry was most often related to breathing laterality (a preferential
      breathing side for a unilateral breathing pattern) and motor laterality (arm
      dominance), with different profiles noted. More than the breathing laterality
      itself, the breathing actions of the non-expert swimmers amplified their
      asymmetric coordination on the breathing side. Conversely, the elite swimmers,
      who had higher and more stable spatial-temporal parameters (velocity and stroke
      lengths), a high coordination value (IdC) and lower breathing frequency (BF),
      managed their race better than the less proficient swimmers and their asymmetric
      arm coordination was not disturbed by breathing actions. By determining the
      dominant arm and the preferential breathing side, the coach can obtain a swimmer
      profile that allows both coach and swimmer to better understand and respond to
      excessive coordination asymmetry.

PMID- 15964649
TI  - Using national microbiological data to set meaningful performance criteria for
      slaughter and dressing of animals at Australian export abattoirs.
AB  - Slaughter establishments in Australia that export meat to the USA are required by
      the controlling authority, the Australian Quarantine and Inspection Service
      (AQIS), to test carcases under the Escherichia coli and Salmonella monitoring
      (ESAM) program and to use statistical process control techniques to ensure meat
      is produced hygienically. However, analysing the ESAM database for E. coli using
      standard statistical techniques proved difficult because of inter-plant
      variability and because the vast majority of results were below the limits of
      detection. As well, it is likely that, in slaughter and dressing, higher than
      normal microbiological counts can often be random events, for which there is
      neither logical explanation nor obvious management reaction. One approach to
      statistical process control is to set performance criteria so that a high
      proportion of establishments are likely to pass, while prompting individual
      plants to improve the process if they cannot meet the criteria. A spreadsheet
      based tool was developed in Visual Basic in order to interrogate the ESAM
      database and to identify those plants with microbiological performance
      significantly different from the norm. The present paper describes how
      performance criteria for cattle, sheep, pigs and goats and for sub-categories
      within a species (e.g. sheep/lambs, cows/bulls) were established.

PMID- 15964650
TI  - Histamine dehydrogenase from Rhizobium sp.: gene cloning, expression in
      Escherichia coli, characterization and application to histamine determination.
AB  - The gene encoding histamine dehydrogenase in Rhizobium sp. 4--9 has been cloned
      and overexpressed in Escherichia coli. The coding region of the gene was 2,079 bp
      and encoded a protein of 693 amino acids with a calculated molecular mass of
      76,732 Da. This histamine dehydrogenase was related to histamine dehydrogenase
      from Nocardioides simplex (54.5% identical), trimethylamine dehydrogenase from
      Methylophilus methylotrophus (39.3% identical) and dimethylamine dehydrogenase
      from Hyphomicrobium X (38.1% identical), which have a covalent 6-S-cysteinyl
      flavin mononucleotide and a [4Fe--4S] cluster as redox cofactors. Sequence
      alignment and a UV-visible absorption spectrum supported the presence of these
      cofactors in this histamine dehydrogenase. The investigation of the enzymatic
      properties suggested that this enzyme exhibited the most excellent substrate
      specificity toward histamine among all amine oxidases or dehydrogenases found to
      date. The recombinant enzyme was able to be used for the colorimetric
      determination of histamine, which gave a linear calibration curve and identical
      data with conventional methods.

PMID- 15964651
TI  - A novel non line-of-sight method for coating hydroxyapatite onto the surfaces of
      support materials by biomineralization.
AB  - A novel method is described for the non line-of-sight coating of hydroxyapatite
      onto polyurethane reticulated foam and titanium discs. This utilises a biofilm of
      Serratia sp. NCIMB 40259 which, when challenged with a solution containing
      calcium chloride and phosphatase substrate, manufactures biofilm-bound material
      identified as hydroxyapatite by X-ray powder diffraction analysis. Non-invasive
      magnetic resonance imaging was used to visualize the biofilm coating throughout
      the foam labyrinth and to measure the thickness of the film within reticulated
      foam cubes in situ. The film developed within the cube matrices was similar to
      that measured on the surface of a glass slide. Using LaPO(4) deposition as a
      model system the metallised biofilm was visualised in two-dimensional slices
      throughout three-dimensional images acquired by magnetic resonance imaging. A
      similar encrustation of hydroxyapatite on the surface of biofilm grown on
      titanium discs was confirmed by scanning electron microscopy. Potential
      applications for bio-hydroxyapatite as possible bone implant precursors are
      discussed.

PMID- 15964652
TI  - In vitro expression, monoclonal antibody and bioactivity for capsid protein of
      porcine circovirus type II without nuclear localization signal.
AB  - We expressed firstly the Capsid protein gene defecting the nuclear localization
      signal (NLS) of Porcine circovirus type II (PCV2) in Escherichia coli as a fusion
      protein with glutathione S-transferase (rGST-dCap protein). The purified rGST
      dCap protein and the recombinant NLS-defected Cap protein of PCV2 (rdCap protein)
      from the purified rGST-dCap protein reacted specifically with swine antiserum to
      PCV2. Furthermore, the obtained monoclonal antibodies (mAbs) to rdCap protein
      were shown to bind to PCV2 particles replicated in PK15 cell and capsid protein
      (Cap protein) of PCV2 expressed in PK15 cells, respectively. mAbs to rdCap
      protein also revealed the neutralizing ability to PCV2 particles. These results
      demonstrated that rGST-dCap protein expressed in E. coli was folded correctly or
      at least partly, and mAbs to rdCap protein possessed the binding epitopes of PCV2
      particles whereas mAbs 4C4 and 3F6 to rdCap protein remained the neutralization
      epitope of PCV2 particle, showing a possibility of neutralizing mAb to rdCap
      protein as an immnuotherapeutic agent and a potential of rGST-dCap protein as a
      vaccine antigen or serodiagnostic reagent.

PMID- 15964653
TI  - Deposition temperature effect on release rate of indomethacin microcrystals from
      microcapsules of layer-by-layer assembled chitosan and alginate multilayer films.
AB  - Indomethacin (IDM) microcrystals sized 5 approximately 10 microm were directly
      encapsulated with nature polysaccharides chitosan (CHI) and sodium alginate (ALG)
      through layer-by-layer (LbL) self-assembly. Due to partial dissolution of IDM in
      the deposition solution, the retention of the IDM microcrystals gradually
      decreased with increasing deposition times and became 47.7% as 10 layers of
      polysaccharides formed. The release rate of the IDM from the microcapsules was
      monitored with UV absorbance. The half release time t(1/2) of IDM in the
      microcapsule increased with the layer number and the initial burst phenomenon was
      relieved after encapsulation. It was found that added NaCl did not affect the
      release rate even up to 0.5 M of its concentration, while increasing the release
      temperature remarkably speeded up the release process. The prolonged release of
      the encapsulated IDM was still observed when the aqueous release solution
      containing 20 vol.% ethanol. It was very significant that increasing deposition
      temperature from 20 to 60 degrees C reduced the release rate efficiently, owing
      to the increase in multilayer thickness and formation of a more perfect
      multilayer film. This finding provides a new and simple method to control the
      permeability of the LbL assembled multilayer films. Because of the
      biodegradability of CHI and ALG and various methods to tune the release rate, the
      LbL self-assembly on drug microcrystals promises high potential for encapsulation
      used in controlled release.

PMID- 15964655
TI  - The hepatitis C virus replicon system: from basic research to clinical
      application.

PMID- 15964654
TI  - Comparison of monomeric and oligomeric transferrin as potential carrier in oral
      delivery of protein drugs.
AB  - Oligomeric transferrin (Tf) was used to investigate the effect that cross-linking
      of transferrin receptors (TfR) has on intracellular trafficking of the Tf-TfR
      complex and to determine whether or not the Tf-oligomer would be a better carrier
      than monomeric Tf for the oral delivery of protein drugs. The intracellular
      retention and transcytosis of the Tf-oligomer was determined by performing pulse
      chase studies on enterocyte-like Caco-2 cells. The intracellular retention of the
      Tf-oligomer was 2-fold higher than that of monomeric Tf while there was no
      significant difference in transcytosis. However, in vivo studies in CF-1 mice
      showed that the plasma concentrations of Tf from the orally administered Tf
      oligomer were approximately 2-, 3- and 60-fold higher than that of orally
      administered monomeric Tf at 24, 48 and 72 h post-administration, respectively.
      In addition, the retention of the Tf-oligomer in the intestine was higher than
      that of monomeric Tf, which was consistent with in vitro studies. Insulin (In),
      when conjugated to the Tf-oligomer (Agg-Tf-S-S-In), was more effective than
      monomeric Tf-In conjugate (Mono-Tf-S-S-In) in reducing blood glucose levels when
      orally administered to streptozotocin (STZ)-induced diabetic rats. Post-oral
      administration of Agg-Tf-In, a delayed onset and prolonged hypoglycemic effect
      was observed. These results demonstrate that the cross-linking of TfR induced by
      the binding of the oligomeric Tf alters the intracellular trafficking and
      increases the intracellular retention of Tf-TfR complexes in polarized Caco-2
      cells. The alteration of TfR trafficking could conceivably have caused the
      increase of insulin transport across the intestinal barrier when Agg-Tf-S-S-In
      was administered orally to STZ-induced diabetic rats. The delayed onset and
      prolonged effect of Agg-Tf-S-S-In in hypoglycemia strongly suggests that the Tf
      oligomer can act as a sustained release carrier in the oral delivery of protein
      and peptide drugs.

PMID- 15964656
TI  - Serum adiponectin correlates with viral characteristics but not histologic
      features in patients with chronic hepatitis C.
AB  - BACKGROUND/AIMS: Adiponectin induces insulin sensitivity and modulates
      inflammatory responses. We thus studied the implications of adiponectin in
      patients with chronic hepatitis C virus (HCV) infection inherently linked to
      insulin resistance. METHODS: We analyzed the association of serum adiponectin
      levels with clinical, virologic, and histologic findings in 95 naive Taiwanese
      patients with chronic hepatitis C before and after antiviral therapy. RESULTS: At
      baseline, 14 (15%) of the 95 patients were obese and 26 (27%) had type 2 diabetes
      mellitus. Fifty-seven patients were infected with HCV genotype 1 and 38 with
      genotype 2. Steatosis and periportal fibrosis was present in 44 (46%) and 69
      (73%), respectively. In multivariate analysis, male gender, insulin resistance,
      high HCV load and genotype 2 were significantly associated with a lower serum
      adiponectin level. In contrast, intrahepatic gene expression of adiponectin
      receptors was higher in genotype 2 compared with genotype 1. Serum adiponectin
      level did not correlate with other clinical or histologic parameters. After
      treatment, change of steatosis also did not correlate with the change of
      adiponectin level (P=0.61). CONCLUSIONS: Adiponectin correlated with hepatitis C
      viral factors at both serum and liver tissue levels. The interactions among
      adiponectin, insulin resistance and chronic HCV infection merit further studies.

PMID- 15964657
TI  - Mitochondrial hepatopathies.

PMID- 15964658
TI  - Failure of hepatitis B vaccination in patients receiving lamivudine prophylaxis
      after liver transplantation for chronic hepatitis B.
AB  - BACKGROUND/AIMS: Lamivudine prophylaxis against hepatitis B virus (HBV)
      reinfection after liver transplantation is associated with recurrence due to
      escape mutants. METHODS: Fifty-two patients on lamivudine prophylaxis at a median
      of 412 days (median, 370-2040 days) after transplantation for chronic HBV-related
      liver disease received two courses of an accelerated schedule of double-dose
      recombinant HBV vaccine. Before vaccination, all patients were seronegative for
      HBsAg, anti-HBs and HBV DNA (by qPCR). Three intramuscular doses of vaccine (40
      microg each) were administered monthly and another identical course was repeated
      after 3 months. Lamivudine (100mg/day) was continued throughout the study.
      RESULTS: After the first course, two patients developed a weak response (anti-HBs
      titre of 12 mIU/mL) that disappeared rapidly. One early responder developed anti
      HBs (27 mIU/mL) again after the second course but the other did not. Two other
      patients developed response (anti-HBs titre of 17 and 103 mIU/mL, respectively)
      giving an overall response rate of 7.7%. The antibody level declined rapidly. At
      the end of the study, one patient who did not respond had developed viral
      breakthrough which was treated with adefovir dipivoxil therapy. CONCLUSIONS:
      Active immunization with two courses of double-dose recombinant HBV vaccine has
      limited efficacy in patients receiving lamividine prophylaxis after liver
      transplantation.

PMID- 15964659
TI  - Clinical, biochemical and morphological features of hepatocerebral syndrome with
      mitochondrial DNA depletion due to deoxyguanosine kinase deficiency.
AB  - BACKGROUND/AIMS: The aim of this study was to delineate the specific clinical,
      biological and liver morphological alterations of the hepatocerebral syndrome due
      to alterations in the deoxyguanosine kinase gene, a rare and severe form of
      mitochondrial DNA depletion syndrome. METHODS: We report seven cases from three
      unrelated families with the same mutation in the deoxyguanosine kinase gene.
      RESULTS: All the patients presented in the first weeks of life with hepatomegaly
      and progressive liver failure that led to death few months later. Major
      psychomotor delay and multidirectional nystagmus were reported shortly after
      onset of the disease. Severe hyperlactacidaemia was constant. Histological
      examination of the liver disclosed a multifocal injury of hepatocytes with
      irregular foamy steatosis, cholestasis, and fibrosis, associated with different
      degrees of hepatosiderosis and glycogen depletion. Liver respiratory chain
      activities were abnormal in all analysed patients and the amount of liver
      mitochondrial DNA was severely decreased. An identical homozygous 4bp GATT
      duplication was identified in the deoxyguanosine kinase gene of all the cases.
      CONCLUSIONS: These patients, together with patients reported in the literature,
      permit to delineate the specific features of the hepatocerebral form of
      mitochondrial DNA depletion syndrome and to differentiate them from other causes
      of neonatal liver failure.

PMID- 15964660
TI  - A multicenter assessment of liver toxicity by MRI and biopsy in IBD patients on 6
      thioguanine.
AB  - BACKGROUND/AIMS: Although 6-thioguanine (6-TG) has been suggested as an effective
      treatment option for patients with inflammatory bowel disease (IBD), the recent
      description of its hepatotoxicity has led to the recommendation not to consider
      this drug. We initiated a multicenter safety study in IBD-patients treated with 6
      TG to investigate hepatic changes by liver biopsy and magnetic resonance imaging
      (MRI). METHODS: Forty-five patients from three European centers treated with 6-TG
      (40-80 mg/d) at least for 8 weeks were enrolled. In all patients liver biopsy and
      MRI were performed. Slides and MR images were independently read by two
      pathologists and radiologists, respectively, and interpreted according to
      predefined criteria by consent. RESULTS: In 8 patients nodular regenerative
      hyperplasia (NRH) was diagnosed by liver biopsy, in 8 additional patients NRH
      could not be excluded due to equivocal pathological findings. MRI demonstrated a
      sensitivity of 77% and a specificity of 72% in the detection of pathohistological
      findings consistent with and/or possibly related to NRH. CONCLUSIONS: Our study
      suggests that 6-TG therapy in IBD patients is associated with NRH of the liver.
      Based on a special MRI protocol, non-invasive diagnosis of NRH with promising
      sensitivity and specificity was demonstrated.

PMID- 15964661
TI  - Inhibition of hepatitis C virus translation and subgenomic replication by siRNAs
      directed against highly conserved HCV sequence and cellular HCV cofactors.
AB  - BACKGROUND/AIMS: Small interfering RNAs (siRNAs) are an efficient tool to
      specifically inhibit gene expression by RNA interference. Since hepatitis C virus
      (HCV) replicates in the cytoplasm of liver cells without integration into the
      host genome, RNA-directed antiviral strategies are likely to successfully block
      the HCV replication cycle. Additional benefit might arise from inhibition of
      cellular cofactors of HCV replication, such as proteasome alpha-subunit 7 (PSMA7)
      or Hu antigen R (HuR). METHODS: In this study, we investigated direct and
      cofactor-mediated inhibition of HCV by a panel of DNA-based retroviral vectors
      expressing siRNAs against highly conserved HCV sequences or the putative HCV
      cofactors PSMA7 and HuR. Effects were determined in HCV IRES-mediated translation
      assays and subgenomic HCV replicon cells. RESULTS: PSMA7- and HuR-directed siRNAs
      successfully inhibited expression of the endogenous genes, and PSMA7 and HuR
      silencing significantly diminished HCV replicon RNA and NS5B protein levels. HCV
      directed siRNAs substantially inhibited HCV IRES-mediated translation and
      subgenomic HCV replication. Combinations of PSMA7- and HuR-directed siRNAs with
      HCV-directed siRNAs revealed additive HCV RNA inhibitory effects in monocistronic
      replicon cells. CONCLUSIONS: A dual approach of direct- and cofactor-mediated
      inhibition of HCV replication might avoid selection of mutants and thereby become
      a powerful strategy against HCV.

PMID- 15964662
TI  - SIRPalpha negatively regulates differentiation of PC12 cell.
AB  - Signal regulatory protein alpha (SIRPalpha) is an Ig superfamily protein whose
      cytoplasmic region contains immunoreceptor tyrosine-based inhibitory motif
      (ITIM), which when tyrosine phosphorylated binds the SH2-domain containing
      phosphatase 2 (SHP-2). Both SIRPalpha and SHP-2 are highly expressed in brain.
      Murine cerebellar cells cultured on SIRPalpha-coated surface exhibit enhanced
      neurite outgrowth and SIRPalpha is localized at sites of synaptogenesis in
      postnatal mouse brain. In this study, we show that nerve growth factor (NGF)
      stimulation resulted in elevated SIRPalpha expression during PC12
      differentiation. We also show that NGF-induced morphological differentiation, but
      not growth arrest response, was inhibited by ectopic SIRPalpha expression. PC12
      cells stably expressing SIRPalpha proliferated more rapidly than mock-transfected
      cells. The activity of c-jun N-terminal kinase (JNK) decreased in SIRPalpha
      transfected PC12 cells, whereas nuclear factor-kappaB (NF-kappaB) activity
      increased. Collectively, our results suggest that SIRPalpha may stabilize
      synaptic connections by inhibiting improper neurite outgrowth and might realize
      its neuronal function, at least in part, by modulating JNK and NF-kappaB
      activity.

PMID- 15964663
TI  - Differential expression of stress response genes in the H-Tx rat model of
      congenital hydrocephalus.
AB  - cDNA rat stress microarrays were used to test the general hypothesis that
      atypical gene expression patterns exist in the brains of Hydrocephalic-Texas (H
      Tx) compared to normal Sprague-Dawley (SD) rats on embryonic day 18. Sixty-two
      percent of the 216 target transcripts were detected in at least 2 of 3
      replicates, with maximum mean fold change (MFC) ratios (H-Tx:SD) in Bcl-2-related
      ovarian killer protein (BOK, 3.07) and peroxisome proliferator-activated receptor
      alpha (PPAR-alpha, 0.04). Five (3.73%) of the 134 detected transcripts were
      elevated and 20 (17.2%) were suppressed more than twofold in H-Tx. MFC ratios for
      stress response, cytoskeleton-motility, and intracellular transducer-effector
      modulator functional classifications were elevated, while MFC ratios for
      transcription and apoptosis groups were suppressed in H-Tx. K-means clustering
      revealed several patterns of gene expression with potential biological relevance
      in apoptosis, intracellular transducer-effector-modulator, metabolism, cell
      cycle, and stress response transcripts. Multiplex RT-PCR methodology, used to
      corroborate the cDNA data, captured four distinct temporal expression patterns on
      embryonic days 16-20 (E16-E20) for HSP27, DnaJ2, HSP47, HSP60, HSP70, HIP,
      HSP90A, and HSP90beta. The discovery of unique chaperone/heat shock expression
      profiles in the embryonic brains of H-Tx and SD rats is a powerful step towards
      the development of novel mechanistic hypotheses in the study of hydrocephalus
      disorders. This is the first study to associate early stress responses with the
      differential expression of chaperones/heat shock protein-related genes using the
      H-Tx model of congenital hydrocephalus.

PMID- 15964664
TI  - alpha-MSH enhances activity-based anorexia.
AB  - Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa
      (AN). In ABA, scheduled feeding in combination with voluntary access to running
      wheels, results in hyperactivity, hypophagia, body weight loss and activation of
      the HPA axis. Since stimulation of the melanocortin (MC) system has similar
      effects, this system is a candidate system involved in ABA. Here it is shown that
      chronic alpha-MSH treatment enhances ABA by increasing running wheel activity
      (RWA), decreasing food intake and increasing HPA axis activation.

PMID- 15964665
TI  - P2X(7) receptor-mRNA and -protein in the mouse retina; changes during retinal
      degeneration in BALBCrds mice.
AB  - A combined real-time PCR/immunohistochemistry study was carried out to
      investigate whether P2X(7) receptors, known to induce apoptosis and necrosis, may
      be causally related to the process of retinal degeneration in BALBCrds mice. In
      the retinae of BALBCrds mice, P2X(7) receptor-mRNA was the highest at an age of
      20-40 days, and declined afterwards. At the same time, the P2X(7) receptor
      message was constantly low in the retina of control BALBC mice until postnatal
      day 100. The receptor-mRNA in total brain tissue of both strains of mice was
      comparable with that of BALBCrds retinae. Double immunofluorescence in
      combination with laser scanning microscopy was used to study the distribution of
      P2X(7) receptor-immunoreactivity (IR) on neurons and different glial cell types
      of the retina. An exclusively neuronal localization of P2X(7)-IR in the ganglion
      cell layer was found by using either anti-neuronal nuclei or microtubule
      associated protein-2 as neuronal markers. There was a slight age-dependent
      decrease in the abundance of neuronal P2X(7)-IR both in BALBCrds or BALBC mice.
      P2X(7)-IR failed to co-localize with any of the non-neuronal markers used to
      stain microglial or Muller glial cells. No P2X(7) receptor-IR was found in the
      retinal ganglion cell layer of P2X(7)(-/-) animals, when compared with the
      control littermates. Hence, we suggest that, in BALBCrds mice, an early up
      regulation of neuronal P2X(7) receptors may cause injury of retinal neurons and
      thereby functionally contribute to the retinal damage.

PMID- 15964667
TI  - Where are the keynote debates in nurse education?

PMID- 15964666
TI  - Cellular environment facilitates protein accumulation in aged rat hippocampus.
AB  - Aging represents the main risk factor to develop Alzheimer disease (AD) and
      protein aggregation constitutes a pathological hallmark thought to be involved in
      the etiology of this disease. Here, we show that, in basal conditions, the
      expression of chaperones calnexin, protein disulfide isomerase (PDI) and Grp78
      was decreased in aged hippocampus, whereas the protein ubiquitination increased,
      suggesting the existence of age-related deficits in the systems involved in the
      defense against unfolded proteins. Interestingly, when cellular stress was
      induced by intra-hippocampal lactacystin injection, the aged rats were less
      efficient than young animals in alleviating the protein accumulation and, as an
      important factor, did not induce the expression of chaperones as young animals.
      However, the expression of the pro-apoptotic factor CHOP/GADD153 was induced and
      caspase-12 was activated in stressed aged rats but not in young animals. Current
      results demonstrated that unfolding protein response (UPR) is not correctly
      activated in aged rat hippocampus. Consequently, the up-regulation of apoptotic
      pathway mediators is increased in aged rats. Results might provide further
      understanding of the pathogenic mechanisms of age-related neurodegenerative
      disorders.

PMID- 15964668
TI  - Estimation of the neuraminidase content of influenza viruses and split-product
      vaccines by immunochromatography.
AB  - The neuraminidase (NA) of the influenza virus, as well as the hemagglutinin, is
      the most important protective components in the vaccine. However, the NA content
      of the vaccine remains to be standardized because of the labile nature of this
      glycoprotein during various chemical treatments and storage. In the present
      study, the NA content of the split-product (SP) vaccine (virus treated with ether
      then formalin) was estimated together with that of the virus by an
      immunochoromatography technique using monoclonal antibodies (mAbs) to viral NA
      for A/Panama/2007/99 (A/Pa) (H3N2), B/Shangdong/7/97 (B/S) or A/New
      Caledonia/20/99 (A/NC) (H1N1) viral strains. In the new method, the NA catalytic
      activity of each fraction from steps of NA purification was measured as an index
      of NA content. The NA level of A/Pa, B/S or A/NC viral particles was estimated at
      6.9+/-0.9, 7.6+/-0.8 or 8.5+/-1.7% of total viral protein (not significant
      difference between viral strains). The NA level of the corresponding A/Pa, B/S or
      A/NC vaccines was estimated at 9.6+/-1.5, 12.7+/-0.4 or 12.2+/-1.2% of the total
      vaccine protein (a significant difference between each strain of virus and its
      vaccine). These results suggest that the NA content in the N1, N2 or B type NA
      virus ranges from 5 to 11% of the total viral protein, and that the NA level in
      each split-product vaccine is 1.4- to 1.6-fold higher than that in the
      corresponding viral particles. They also suggest that the NA content can be
      estimated by the immunochoromatography technique using anti-viral NA mAbs.

PMID- 15964669
TI  - Improved intranasal immunization with live-attenuated measles virus after co
      inoculation of the lipopeptide MALP-2.
AB  - The macrophage-activating lipopeptide with a molecular weight of 2kDa (MALP-2)
      activates antigen presenting cells of human, mouse and rat origin in vitro and in
      vivo. Here, we demonstrate that MALP-2 induces MIP1alpha and beta, MIP-2, Gro,
      TNFalpha, IL1alpha and IL6 in cells of cotton rats (Sigmodon hispidus) in vitro.
      Intranasal inoculation into cotton rats leads to migration of neutrophils and
      other leucocytes into the lung lumen and lung tissue. After intranasal co
      inoculation of MALP-2 with live-attenuated measles vaccine virus, higher titers
      of neutralizing antibodies are induced but the proliferative T cell response did
      not increase. Immunization leads to protective immunity in the absence, but not
      in the presence of passively transferred measles virus (MV) specific antibodies.

PMID- 15964670
TI  - RNA interference-based (RNAi) suppression of AtMPK6, an Arabidopsis mitogen
      activated protein kinase, results in hypersensitivity to ozone and misregulation
      of AtMPK3.
AB  - The recent increase in tropospheric ozone (O(3)) concentrations promotes
      additional oxidative stress through the production of reactive oxygen species
      (ROS) in plant tissues, resulting in the activation of genes whose products
      enable the stressed cells to retain their integrity and function. This response
      is made possible by an integration of highly regulated signaling networks that
      mediate the perception of, and response to, this oxidative assault. In
      Arabidopsis thaliana, ROS-induced signaling has been shown to flow through a
      protein phosphorylation cascade involving the mitogen-activated protein kinases
      (MAPKs) AtMPK3 (MPK3) and AtMPK6 (MPK6). We found that RNAi-mediated silencing of
      MPK6 renders the plant more sensitive to ozone, as determined by visible leaf
      damage. The MPK6-RNAi genotype also displayed a more intense and prolonged
      activation of MPK3 compared to that of WT plants. An MPK3 loss-of-function
      genotype is similarly very sensitive to ozone, and displays an abnormally
      prolonged MPK6 activation profile, suggesting reciprocity in regulation between
      these two MAPKs.

PMID- 15964671
TI  - The capacity to consent to treatment and research: a review of standardized
      assessment tools.
AB  - The use of standardized tools for the assessment of competency is vital, given
      that informal assessments performed by physicians are idiosyncratic and
      unreliable []. A number of instruments have been developed for this purpose,
      which are outlined in the following review. For the most part, these tools rest
      on a definition of competency put forward by Appelbaum and Roth [Appelbaum, P.
      S., & Roth, L. H. (1982). Competency to consent to research. A psychiatric
      overview. Archives of General Psychiatry, 39, 951-958], which incorporates
      various legal standards. Therefore, the present review will summarize current
      thinking on competence as well as the strengths, weaknesses, and psychometric
      properties of existing measures. As competency assessment will be more or less
      necessary depending on the patient population, another goal of the paper was to
      assemble the major findings pertaining to patient groups that have impairments in
      capacity. Although competency varies between and within diagnostic groups,
      empirical studies consistently demonstrate increased risk for some populations,
      and clinicians or researchers should be aware of this information. As such, this
      review may be useful as an initial source for interested researchers or
      clinicians.

PMID- 15964672
TI  - A narrative approach to understanding the nursing work environment in Canada.
AB  - Narrative interviews were conducted with hospital nurses participating in a
      research study designed to provide support and assistance to hospitals as they
      addressed work life issues for nurses in an attempt to create quality work
      environments. The eight interviews were conducted in a sample of Canadian
      hospitals and generated themes relating to an imbalance between the effort that
      nurses put into their work and rewards attained from it. Seigrist's ((1996)
      Journal of Occupational Health Psychology, 1, 27-41, (2002) In: P.L. Perrewe &
      D.G. Ganster (Eds.), Historical perspectives on stress and health. Research in
      Occupational Stress and Well Being (vol. 2). Boston, MA: Jai Press) effort-reward
      imbalance model was used to frame this study. The nurses' narratives suggest that
      multiple factors constitute the nurses' work environment and their experiences
      and perceptions of it. Issues which surfaced repeatedly in the interviews related
      to changing needs of hospitalized patients in today's health care system and the
      associated workload, the widespread shortage of nurses, and the imbalance this
      creates for nursing work. A crucial finding is the extent to which the nurse is
      impacted by the adequacy of care they are able to provide. These narratives
      outline the tremendous burden of guilt and the overcommitment that nurses bear
      when factors in the work environment prevent them from providing complete,
      quality care. Nurses are experiencing frustration and stress that is impacting
      their worklife, family and home life, personal health, and possibly patient
      outcomes.

PMID- 15964673
TI  - 2-Nitrosoamino-3-methylimidazo[4,5-f]quinoline activated by the inflammatory
      response forms nucleotide adducts.
AB  - Heterocyclic amines and inflammation have been implicated in the etiology of
      colon cancer. We have recently demonstrated that during autoxidation of the
      inflammatory mediator nitric oxide 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)
      undergoes nitrosation to form 2-nitrosoamino-3-methylimidazo[4,5-f]quinoline (N
      NO-IQ). This study evaluates the genotoxicity of N-NO-IQ and compares the adducts
      it forms to those of 2-hydroxyamino-3-methylimidazo[4,5-f]quinoline (N-OH-IQ). N
      NO-IQ was incubated with 2'-deoxyguanosine 3'-monophosphate (dGp) under a variety
      of inflammatory conditions. 32P-Postlabeling demonstrated the presence of
      multiple adducts. Incubation of N-OH-IQ with dGp at pH 7.4, 5.5, or 2.0 resulted
      in the formation of a single major adduct, N-(deoxyguanosin-8-yl)-IQ (dG-C8-IQ).
      Using a combination of 32P-postlabeling, HPLC, and nuclease P1 treatment, N-NO-IQ
      was shown to produce dG-C8-IQ under several different conditions. HOCl oxidation
      of N-NO-IQ increased dG-C8-IQ formation, and this was further increased as pH
      decreased from 7.4 to 5.5. Oxidation of N-NO-IQ formed a new adduct, adduct 2,
      while in the absence of oxidants adduct m was the major adduct. Adducts 2 and m
      were not formed by N-OH-IQ and not further identified. The results demonstrate
      that N-NO-IQ forms N-(deoxyguanosin-8-yl)-IQ, is genotoxic, is activated by
      conditions that mediate inflammatory responses, and is a possible cancer risk
      factor for individuals with colitis, inflammation of the colon.

PMID- 15964674
TI  - Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin
      induced diabetes in rats.
AB  - Abnormalities in lipid profile are one of the most common complications in
      diabetes mellitus, which is found in about 40% of diabetics. In the present
      study, anti-hyperlipidemic efficacy of Eugenia jambolana seed kernel (EJs-kernel)
      was evaluated in streptozotocin (STZ)-induced diabetic rats and the efficacy was
      compared with standard hypoglycemic drug, glibenclamide. The effect of oral
      administration of ethanolic extract of EJs-kernel (100 mg/kg body weight) was
      examined on the levels of cholesterol, phospholipids, triglycerides and free
      fatty acids in the plasma, liver and kidney tissues of STZ (55 mg/kg body weight)
      induced diabetic rats. The plasma lipoproteins and tissues fatty acid composition
      were also monitored. STZ-induced diabetic rats, showed significant increase in
      the levels of cholesterol, phospholipids, triglycerides and free fatty acids
      which were considerably restored to near normal in EJs-kernel or glibenclamide
      treated animals. The plasma lipoproteins (HDL, LDL, VLDL-cholesterol) and fatty
      acid composition were altered in STZ-induced diabetic rats and these levels were
      also reverted back to near normalcy by EJs-kernel or glibenclamide treatment. It
      may be concluded that, EJs-kernel possesses hypolipidemic effect, which may be
      due to the presence of flavonoids, saponins, glycosides and triterpenoids in the
      extract. The hypolipidemic effect mediated by EJs-kernel may also be anticipated
      to have biological significance and provide a scientific rationale for the use of
      EJs-kernel as an anti-diabetic plant.

PMID- 15964675
TI  - Melatonin protects against lead-induced hepatic and renal toxicity in male rats.
AB  - The present study was designed to investigate the potential protective effect of
      melatonin against the hepatic and renal toxicity of lead in male rats. Three
      groups of animals were used in this study (control, lead acetate-treated (100
      mg/kg), and lead acetate plus melatonin (10 mg/kg) for 30 days. Levels of lipid
      peroxidation (LPO) products, superoxide dismutase (SOD) activity, total
      glutathione (GSH), histopathological changes in the liver and kidneys were
      investigated. In addition, nuclear area (NA), nuclear volume (NV) and the ratio
      of nuclear volume/cellular volume (N/C) were measured in the liver. The results
      revealed increased LPO and decreased SOD, GSH, NA, NV and N/C in the studied
      organs of lead-treated rats. Histopathological observations showed severe damage
      in the liver and kidneys. Melatonin co-treatment to the lead-administered rats
      attenuated the increase of LPO and restored the activity of SOD and levels of GSH
      as well as the mean values of NA, NV and N/C. Also, the morphological damage in
      the liver and kidneys was reduced and the tissues appeared like those of
      controls. The present study suggests that melatonin may be useful in combating
      free radical-induced damage due to lead toxicity.

PMID- 15964677
TI  - Minocycline does not inhibit microglia proliferation or neuronal regeneration in
      the facial nucleus following crush injury.
AB  - Minocycline is thought to be neuroprotective by inhibiting neuroinflammation
      (microglial activation) associated with neurodegenerative diseases. In this study
      we investigated the effect of minocycline specifically on microglial mitotic
      activity and neuronal regeneration within the facial nucleus following a nerve
      crush injury. Proliferation was measured by labeling the dividing microglia with
      3H-thymidine and quantifying labeled cells throughout the facial nucleus on days
      2, 3 and 4 post-axotomy. Regeneration patterns of the axotomized motoneurons were
      studied by labeling regenerating neurons with fluorogold at 7, 14 and 21 days
      post-axotomy. No significant difference was found between minocycline treated and
      control rats when comparing the 3H-thymidine labeled microglial cells or
      fluorogold labeled neurons at these post-injury time points. The findings show
      that microglia maintain the ability to become activated in vivo even in the
      presence of high levels of minocycline.

PMID- 15964678
TI  - The plasticity of gravitational reference frame and the subjective vertical:
      peripheral visual information affects the oblique effect.
AB  - The experiment examined the human visual perception of orientations and the
      nature of reference frame in which the oblique effect (lower performance in
      oblique orientations than in vertical or horizontal ones) was defined. Previous
      research [M. Luyat, E. Gentaz, Body tilt effect on the reproduction of
      orientations: studies on the visual oblique effect and subjective orientations,
      J. Exp. Psychol. Hum. Percept. Perform. 28 (2002) 1002-1011. M. Luyat, E. Gentaz,
      T.R. Corte, M. Guerraz, Reference frames and haptic perception of orientation:
      body and head tilt effects on the oblique effect, Percept. Psychophys. 63 (2001)
      541-554], using head tilt paradigm to uncouple the gravitational, egocentric and
      subjective reference frames, showed that the oblique effect was mapped in a
      subjective gravitational reference frame with the subjective vertical as a
      cardinal orientation. However, the subjective vertical is not only affected by
      the tilt of head but also by the tilt of visual context. Then, the tilt of visual
      oriented cues is another paradigm permitting to evidence the role of the
      subjective gravitational reference frame. Sixteen participants were asked to
      reproduce five different orientations of a luminous line: horizontal (0 degrees
      ), 45 degrees (oblique), 90 degrees (vertical), 135 degrees (oblique) and the
      subjective vertical. These orientations were reproduced with no visual contextual
      cues and with tilted visual contextual cues tilted 15 degrees either to the left
      or to the right. The results showed that the oblique effect decreased with tilted
      visual contexts but was not completely suppressed. These results proved that this
      oblique effect is defined in a multimodal reference frame which integrates not
      only vestibular and proprioceptive cues but also peripheral visual information.

PMID- 15964679
TI  - Lactic acidosis stimulates ganglioside and ceramide generation without
      sphingomyelin hydrolysis in rat cortical astrocytes.
AB  - Acidosis is a ubiquitous feature of cerebral ischemia, and triggers a cascade of
      biochemical events that results in neuronal injury. The purpose of this study was
      to evaluate the effects of lactic acidosis on the ganglioside composition, the
      ceramide and sphingomyelin (SM) levels in rat cortical astrocytes. Primary
      astrocyte cultures were exposed to lactic acid (pH 5.5) for 2, 5 and 17 h, and
      cell death was evaluated at each time point. Gangliosides, ceramides and SM were
      analyzed by high-performance thin layer chromatography. Lactic acidosis caused a
      progressive increase of both GM3 and GD3 gangliosides up to 5 h of treatment.
      However, at 17 h of acidosis, GM3 tented to return to the normal level whereas
      GD3 accumulated. Additionally, ceramides were gradually generated, whereas no
      significant decrease of SM occured for 17 h of acidosis. These results suggest
      that ceramides were not produced by the breakdown of SM and may be served as
      metabolic precursor for the biosynthesis of GM3 and GD3. Since these lipids are
      important messengers of the adaptative responses to stress, accumulation of
      sphingolipids triggered by lactic acid exposure of astrocytes might play an
      important role in determining the outcomes of injurious processes.

PMID- 15964680
TI  - Imaging the dynamics of the auditory steady-state evoked response.
AB  - This study used magnetoencephalography (MEG) to examine the dynamic patterns of
      neural activity underlying the auditory steady-state response. We examined the
      continuous time-series of responses to a 32-Hz amplitude modulation. Fluctuations
      in the amplitude of the evoked response were found to be mediated by non-linear
      interactions with oscillatory processes both at the same source, in the alpha and
      beta frequency bands, and in the opposite hemisphere.

PMID- 15964681
TI  - Changes in cerebrospinal fluid levels of pro-inflammatory cytokines in CRPS.
AB  - Complex Regional Pain Syndrome (CRPS) Types I and II are characterized by various
      combinations of sensory, autonomic and motor abnormalities. Pain disproportionate
      to the severity and duration of the inciting event is the most devastating
      symptom. In animal studies, conditions resulting in exaggerated pain states
      demonstrate elevated pro-inflammatory cytokines. In addition, pro-inflammatory
      cytokines have been shown to induce or increase neuropathic and inflammatory
      pain. Utilizing high sensitivity enzyme linked immunosorbent assay (ELISA), we
      compared the levels of the pro-inflammatory cytokines interleukin-1beta (IL
      1beta), interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha) in the
      cerebrospinal fluid (CSF) of patients afflicted with CRPS to CSF levels found in
      other patients with and without painful conditions. The results from this study
      demonstrated significant increases in IL-1beta and IL-6, but not TNF-alpha in the
      CSF of individuals afflicted with CRPS as compared to controls. CSF cytokine
      levels in controls with painful conditions did not differ from levels in controls
      without pain. These increases showed no correlation with the patient's gender or
      weight. These results are consistent with studies that suggest that the
      pathogenesis of CRPS is due in part to central neuroimmune activation.

PMID- 15964682
TI  - Cluster analysis of multiple experimental pain modalities.
AB  - Identifying individual differences in pain is an important topic; however, little
      is known regarding patterns of responses across various experimental pain
      modalities. This study evaluated subgroups emerging from multiple experimental
      pain measures. One hundred and eighty-eight individuals (59.0% female) completed
      several psychological instruments and underwent ischemic, pressure, and thermal
      pain assessments. Thirteen separate pain measures were obtained by using three
      experimental pain modalities with several parameters tested within each modality.
      The pain ratings and scores were submitted to factor analysis that identified
      four pain factors from which Pain Sensitivity Index (PSI) scores were computed:
      heat pain (HP), pressure pain (PP), ischemic pain (IP), and temporal summation of
      heat pain (TS). Cluster analyses of PSI scores revealed four distinct clusters.
      The first cluster demonstrated high overall pain sensitivity, the second cluster
      revealed high TS, the third cluster showed particular insensitivity to IP and low
      sensitivity across pain modalities except PP, and the fourth cluster demonstrated
      low sensitivity to PP. Significant correlations were found between psychological
      measures and Index scores and those differed by sex. Cluster membership was
      associated with demographic variables of ethnicity and sex as well as specific
      psychosocial variables, although cluster differences were only partially
      explained by such factors. These analyses revealed that groups respond
      differently across varied pain stimuli, and this was not related solely to
      demographic or psychosocial factors. These findings highlight the need for future
      investigation to identify patterns of responses across different pain modalities
      in order to more accurately characterize individual differences in responses to
      experimental pain.

PMID- 15964683
TI  - Referred pain pattern of the pronator quadratus muscle.
AB  - Pain patterns of the myofascial trigger points (TrP) for most muscles of the
      forearm have been documented. However, there are no published reports on the
      referred pain patterns for the pronator quadratus (PQ) muscle. The purpose of
      this study was to determine the referred pain pattern of the TrP in the PQ.
      Thirty-five arms of 35 healthy adult volunteers with no history of neck pain, arm
      pain or paresthesia were studied. Following skin sterilization, a Teflon-coated
      syringe needle was inserted into the PQ of the non-dominant forearm under
      electromyographic guidance, and 0.3mL of 6% hypertonic saline was injected.
      Subjects drew in their pain areas on a pain diagram, and this drawing was
      transferred into the Pain Chart System for analysis. Two main pain patterns were
      observed. The most common pattern involved pain spreading both distally and
      proximally from the injection site, along the medial aspect of the forearm (57%).
      In half of these cases, the pain area extended to the medial epicondyle
      proximally and the fifth digit distally. The second main pattern revealed pain
      spreading distally to the third and/or fourth finger (29%). The pain patterns
      originating from the PQ resemble the C8-T1 dermatomes, and ulnar and median nerve
      sensory distributions. Thus, myofascial pain of the PQ should be considered as a
      possible cause of pain in the medial forearm and hand, especially when no other
      neurological abnormalities are present.

PMID- 15964685
TI  - Psychological distress and opioid efficacy: more questions than answers.

PMID- 15964684
TI  - Role of NK-1 neurotransmission in opioid-induced hyperalgesia.
AB  - Opiates are among the most important drugs for treatment of moderate to severe
      pain and prolonged opiate administration is often required to treat chronic pain
      states. We investigated the neurobiological actions of sustained opiate
      administration revealing paradoxical pronociceptive adaptations associated with
      NK-1 receptor function. Sustained morphine delivered over 6 days elicited
      hyperalgesia in rats and mice during the period of opiate delivery. Sustained
      morphine administration increased substance P (SP) and NK-1 receptor expression
      in the spinal dorsal horn. Sustained morphine treatment also enhanced capsaicin
      evoked SP release in vitro, and increased internalization of NK-1 receptors in
      response to noxious stimulation. While NK-1 receptor internalization was observed
      primarily in the superficial laminae of placebo-treated rats, NK-1 receptor
      internalization was seen in both superficial and deep lamina of the dorsal horn
      in morphine-treated animals. Morphine-induced hyperalgesia was reversed by spinal
      administration of an NK-1 receptor antagonist in rats and mice, and was observed
      in wildtype (NK-1(+/+)), but not NK-1 receptor knockout (NK-1(-/-)), mice. These
      data support a critical role for the NK-1 receptor in the expression of sustained
      morphine-induced hyperalgesia. Additionally, these data indicate that sustained
      opiate administration induces changes reminiscent of those associated with
      inflammatory pain. These opiate-induced changes might produce unintended
      deleterious actions in the course of pain treatment in patients. Understanding of
      sustained morphine-induced neurochemical changes will help identify approaches
      that limit the deleterious actions of opiates.

PMID- 15964686
TI  - Reduction of pain-related fear in complex regional pain syndrome type I: the
      application of graded exposure in vivo.
AB  - Fear of (re)injury/movement has been identified as a potential predictor of
      chronic disability in complex regional pain syndrome type I (CRPS-I). In order to
      reduce pain-related fears and pain disability, graded exposure in vivo (GEXP) is
      likely to be an appropriate treatment. Indeed, there is evidence that in chronic
      pain patients reporting substantial fear of (re)injury/movement, GEXP is
      successful in reducing pain disability. However, the efficacy of exposure-based
      protocols in the treatment of CRPS-I patients for reducing pain disability has
      not been tested. The main research question of this study was whether the
      reduction of pain-related fear through GEXP also resulted in a decrease of
      disability in a subgroup of patients with CRPS-I who report substantial pain
      related fear. A single-case experimental ABCD-design was used with random
      determination of the start of the intervention. Eight patients with CRPS-I were
      included in the study. To assess daily changes in pain intensity, pain-related
      fear, pain catastrophizing, and activity goal achievement, a diary was used.
      Standardized questionnaires of pain-related fear, pain disability, and self
      reported signs and symptoms of CRPS-I were administered before and after each
      intervention, and at 6-month follow-up. The current study supports a GEXP
      approach to chronic CRPS-I. The GEXP was successful in decreasing levels of self
      reported pain-related fear, pain intensity, disability, and physiological signs
      and symptoms. These results support the hypothesis that the meaning people attach
      to a noxious stimulus influences its experienced painfulness, and that GEXP
      activates cortical networks and reconciles motor output and sensory feedback.

PMID- 15964688
TI  - Associations between dairy herd management factors and bulk tank milk antibody
      levels against Ostertagia ostertagi.
AB  - A cross-sectional questionnaire survey was performed on dairy herds in Flanders
      (Belgium) to detect management factors that are associated with an increased
      gastrointestinal parasite infection level of adult dairy cows. At the end of the
      grazing season, information concerning general herd factors, pasture management
      and anthelmintic treatment strategy was obtained from 956 herds. A bulk tank milk
      sample was obtained from 779 out of the 956 herds and the antibody levels (ODR)
      against Ostertagia ostertagi were determined. The associations between ODR and
      herd management factors were studied by two linear regression models. The first
      model evaluated the effect of general herd factors and the level of the cows'
      exposure to pasture. Large sized herds had significantly lower ODRs as compared
      to medium (P=0.001) or small sized herds (P=0.03). Herds with only dairy cows had
      lower ODRs than herds with both dairy and beef cows (P=0.02). An increased
      exposure to pasture of the cows was associated with higher ODRs (P<0.001). The
      second model was built to evaluate the effect of pasture management factors and
      anthelmintic treatment strategy. Later turn-out on pasture (P<0.001) and mowing
      (P=0.002) were both significantly associated with lower ODRs. Cows that had a
      restricted grazing time per day tended to have lower ODR than cows that grazed 24
      h per day (P=0.07). An increased exposure to pasture of the heifers was
      significantly associated with higher ODRs (P=0.001). No associations were found
      between ODR and calf related management factors, anthelmintic treatment strategy,
      time of turn-in, rotational grazing type or stocking rate. Later turn-out on
      pasture, mowing and restricting the grazing time per day are factors that can be
      applied immediately on dairy farms to reduce economical losses due to
      gastrointestinal nematodes.

PMID- 15964687
TI  - Neuropathic pain: early spontaneous afferent activity is the trigger.
AB  - Intractable neuropathic pain often results from nerve injury. One immediate event
      in damaged nerve is a sustained increase in spontaneous afferent activity, which
      has a well-established role in ongoing pain. Using two rat models of neuropathic
      pain, the CCI and SNI models, we show that local, temporary nerve blockade of
      this afferent activity permanently inhibits the subsequent development of both
      thermal hyperalgesia and mechanical allodynia. Timing is critical-the nerve
      blockade must last at least 3-5 days and is effective if started immediately
      after nerve injury, but not if started at 10 days after injury when neuropathic
      pain is already established. Effective nerve blockade also prevents subsequent
      development of spontaneous afferent activity measured electrophysiologically.
      Similar results were obtained in both pain models, and with two blockade methods
      (200mg of a depot form bupivacaine at the injury site, or perfusion of the
      injured nerve just proximal to the injury site with TTX). These results indicate
      that early spontaneous afferent fiber activity is the key trigger for the
      development of pain behaviors, and suggest that spontaneous activity may be
      required for many of the later changes in the sensory neurons, spinal cord, and
      brain observed in neuropathic pain models. Many pre-clinical and clinical studies
      of pre-emptive analgesia have used much shorter duration of blockade, or have not
      started immediately after the injury. Our results suggest that effective pre
      emptive analgesia can be achieved only when nerve block is administered early
      after injury and lasts several days.

PMID- 15964689
TI  - Immunoblot analysis of specific antigen bands predictable for Dirofilaria immitis
      infection in cats.
AB  - Serial sera from four mongrel cats experimentally inoculated with infectious
      larvae of Dirofilaria immitis were analyzed by immunoblot patterns against a
      phosphate buffered saline-extract of D. immitis. Antigen-specific protein bands
      detected indicate that the low molecular weight bands of 36, 32, 22, 19 and 14
      kDa, are predictable for positive adult worm infection, suggesting diagnostic
      usefulness for adult D. immitis infection in cats.

PMID- 15964690
TI  - An alternative method of blood-feeding Culicoides imicola and other
      haematophagous Culicoides species for vector competence studies.
AB  - The use of cotton wool pads saturated with blood/virus mixture for oral infection
      attempts was compared to membrane feeding for the assessment of vector competence
      in C. imicola Kieffer and C. bolitinos Meiswinkel (Diptera, Ceratopogonidae).
      Although lower infection rates were obtained using pad feeding, it was possible
      to clearly distinguish the levels of competence between species as well as
      differences in virus infection rates for various serotypes of bluetongue virus.
      Reduced infection rates with cotton pad feeding was partly due to a smaller
      volume of blood meals taken up. However, the method described is likely to be
      useful in situations where membrane feeding is not viable to separate populations
      with significant differences in vector competence.

PMID- 15964691
TI  - Preparation and characterization of active site protected poly(ethylene glycol)
      avidin bioconjugates.
AB  - Avidin was modified with poly(ethylene glycol) in the presence of a biotin
      binding site protective agent synthesised by imminobiotin conjugation to branched
      20 kDa PEG. Avidin was incubated with imminobiotin-PEG and reacted with high
      amounts of 5, 10 or 20 kDa PEG to modify the protein amino groups. Circular
      dichroism demonstrated that the extensive PEGylation does not alter the protein
      conformational structure. The affinity of avidin-PEG conjugates for biotin and
      biotinylated antibodies depended on the PEG size or the use of a protective
      agent. Avidin-PEG 10 and 20 kDa prepared in the presence of imminobiotin-PEG
      maintained 100% of the native affinity for biotin. The 5 kDa PEG derivative and
      the ones obtained without biotin site protection maintained 79-85% of the native
      affinity. The affinity for biotinylated antibodies decreased to 35% when the
      conjugation was performed without imminobiotin-PEG, while the conjugates obtained
      with high-molecular-weight PEGs in the presence of protective agent displayed
      high residual affinity. All conjugates possessed negligible antigenicity and
      immunogenicity. PEGylation greatly prolonged the avidin permanence in the
      circulation, reduced its disposition in the liver and kidneys and promoted
      accumulation into solid tumors. PEGylation was found to prevent the protein cell
      uptake, either by phagocytosis or pinocytosis.

PMID- 15964692
TI  - Ultraviolet radiation-induced apoptosis in keratinocytes: on the role of
      cytosolic factors.
AB  - Epidemiological and experimental evidences have established solar ultraviolet
      (UV) radiation as the leading cause of skin cancers. Specifically, the frequency
      of non-melanoma skin cancer, one of the malignancies with the most rapidly
      increasing incidence, is directly related to the total exposure to solar UV
      light. As part of a general effort to elucidate the components of cellular signal
      transduction pathways, the mechanisms of cellular responses to UV radiation have
      received considerable attention over the last few years. These efforts were
      driven mainly by the conviction that understanding how normal cells respond to
      extracellular stimuli such as exposure to UV radiation will undoubtedly help in
      deciphering what goes wrong in a variety of clinical disorders including skin
      cancers and will assist in the development of novel therapeutic strategies.
      Studies over the last decade have established that UV radiation induces a
      bewildering array of signal transduction pathways, some of which could lead to
      apoptotic cell death. UV-induced cell death by apoptosis is considered to be a
      natural protective mechanism that removes damaged keratinocytes and circumvents
      the risk of malignant transformation. In this review, we summarize some of the
      most important findings regarding the response and role of mitogen-activated
      protein kinases in UVA and UVB radiation-induced signaling to apoptosis in
      keratinocytes. We will also briefly discuss what is known about the role of the
      BCL-2 family of proteins, the emerging role of lysosomal proteases and other
      important cytosolic signaling proteins in UV-induced apoptosis.

PMID- 15964693
TI  - Thalamic nucleus submedius receives GABAergic projection from thalamic reticular
      nucleus in the rat.
AB  - GABAergic projection from thalamic reticular nucleus to thalamic nucleus
      submedius in the medial thalamus of the rat was studied by using
      immunohistochemistry for GABA, retrograde labeling with Fluoro-Gold combined with
      immunohistochemistry for GABA, and anterograde labeling with biotinylated
      dextranamine. Immunohistochemistry displayed that only GABA immunoreactive
      terminals were observed in the thalamic nucleus submedius, while GABA
      immunoreactive neuronal cell bodies were located in the thalamic reticular
      nucleus and lateral geniculate nucleus. Injection of Fluoro-Gold into the
      thalamic nucleus submedius resulted in massive retrogradely labeled neuronal cell
      bodies in the rostroventral portion of the ipsilateral thalamic reticular nucleus
      and a few in the contralateral thalamic reticular nucleus, and most of these cell
      bodies showed GABA immunopositive staining. Many biotinylated dextranamine
      anterogradely labeled fibers and terminals in the thalamic nucleus submedius were
      observed after injection of biotinylated dextranamine into the thalamic reticular
      nucleus. The present results provide a morphological evidence for a hypothesis
      that a disinhibitory effect on output neurons elicited by opioid or 5
      hydroxytryptamine inhibiting a GABAergic terminal in the thalamic nucleus
      submedius may lead to activation of the descending inhibitory system and
      depression of the nociceptive inputs at the spinal cord level.

PMID- 15964694
TI  - Circadian and light regulation of oxytocin and parvalbumin protein levels in the
      ciliated ependymal layer of the third ventricle in the C57 mouse.
AB  - The walls of the third ventricle have been proposed to serve as a bidirectional
      conduit for exchanges between the neural parenchyma and the cerebrospinal fluid.
      In immunohistochemical studies of mice, we observed that light exposure and
      circadian phase affected peptide staining surrounding the third ventricle at the
      level of the suprachiasmatic nuclei. Under high magnification, we observed robust
      staining for the neurohormone oxytocin and the calcium-binding protein
      parvalbumin associated with cilia extending into the third ventricle from the
      surrounding ventricular wall; no similar staining was observed for vasopressin or
      calbindin. Retinal illumination had opposite effects on levels of parvalbumin and
      oxytocin in the cilia: light exposure during late subjective night increased
      oxytocin staining, but decreased parvalbumin staining in the cilia. Preventing
      cellular transport with colchicine eliminated immunohistochemical staining for
      oxytocin in the cilia. There was also a significant daily rhythm of oxytocin
      immunostaining in the third ventricle wall, and in magnocellular neurons in the
      anterior hypothalamus. The results suggest that environmental lighting and
      circadian rhythms regulate levels of oxytocin in the cerebrospinal fluid,
      possibly by regulating movement of oxytocin through the third ventricle wall.

PMID- 15964695
TI  - Extracellular signal-regulated kinase-1 and -2 are activated by gastric luminal
      injury in dorsal root ganglion neurons via N-methyl-D-aspartate receptors.
AB  - Mitogen activated protein kinases such as phosphorylated extracellular signal
      regulated kinase-1 and -2 (pERK 1/2) have been recently demonstrated to play an
      important role in somatic nociception and hyperalgesia. In the present study we
      examined whether pERK 1/2 is involved in the response of sensory neurons to a
      noxious visceral stimulation, in particular, of the gastric mucosa. After
      induction of gastric injury by oral administration of 0.5M HCl pERK 1/2
      expression was determined by Western blotting of caudal thoracic dorsal root
      ganglia and by immunohistochemistry in stomach-innervating dorsal root ganglion
      neurons which were retrogradely labeled with True Blue. The content of pERK 1/2
      remained unchanged in dorsal root ganglia until 2 h post-HCl, however, was found
      elevated 4 (approximately 80%) and 6 h (approximately 100%) after HCl
      administration. True Blue-labeled pERK 1/2-immunoreactive neurons were likewise
      increased 6 h post-HCl (204%) and were mainly of small size (20-40 microm) and
      negative for neurofilament 200 (approximately 76%). The majority of these cells
      also expressed the nociceptive transient receptor potential vanilloid receptor 1
      (approximately 70%). The gastric mucosa was simultaneously examined for lesion
      formation showing highest percentage of damage 6 h post-HCl. Application of a N
      methyl-D-aspartate receptor antagonist (MK-801; 100 microg/kg s.c.) significantly
      reduced HCl-induced pERK 1/2 expression and mucosal lesions 6 h post-HCl.
      Activation of the extracellular signal-regulated kinase-1 and -2 signaling
      cascade indicates that visceral primary afferents may sensitize after gastric
      noxious stimulation involving N-methyl-D-aspartate receptors. The extracellular
      signal-regulated kinase-1 and -2 pathway therefore may not only be of importance
      for somatic but also for visceral nociception.

PMID- 15964696
TI  - Lesional accumulation of P2X(4) receptor(+) macrophages in rat CNS during
      experimental autoimmune encephalomyelitis.
AB  - P2X(4) receptor (P2X(4)R) is an ion channel gated by ATP. Here we report the
      presence and distribution of P2X(4)R by immunohistochemical analysis of the rat
      CNS. In normal control rats, P2X(4)R was expressed by perivascular cells, but not
      found on parenchymal monocytic cells. We further investigated P2X(4)R expression
      in experimental autoimmune encephalomyelitis. P2X(4)R(+) cells were mainly
      identified as infiltrative macrophages in CNS lesions. In the diseased brain,
      P2X(4)R(+) leukocytic cells were not only found in the direct vicinity of the
      inflammatory infiltrate, but widespread distribution was seen in the parenchyma.
      In experimental autoimmune encephalomyelitis spinal cord, the number of
      P2X(4)R(+) cells was much higher than in brain. P2X(4)R(+) macrophage
      accumulation reached the maximal levels around day 14 correlating to the clinical
      severity of experimental autoimmune encephalomyelitis, and this upregulation
      lasted until the recovery stage of the disease. This implicates a role of P2X(4)R
      in the inflammatory process of the CNS. In addition, bromodeoxyuridine
      immunohistochemistry was employed to demonstrate cell proliferation. Only few
      bromodeoxyuridine+/P2X(4)R+ monocytes/macrophages were observed in both the
      diseased brain and spinal cord. In conclusion, this is the first demonstration
      that P2X(4)R presents in autoimmune-lesioned CNS. Consequently, P2X(4)R might be
      a valuable marker to dissect the local monocyte heterogeneity in autoimmune
      disease.

PMID- 15964697
TI  - Role of cyclin-dependent kinase 5 and its activator P35 in local axon and growth
      cone stabilization.
AB  - Axons elongate and perform steering reactions with their growth cones constantly
      undergoing local collapse and stabilization. Our previous studies have shown that
      a type-1 phosphorylated form of microtubule-associated protein 1B, recognized by
      monoclonal antibody 1E11 (mab1E11), is present in stable regions and absent from
      unstable regions of turning growth cones of retinal ganglion cells. In contrast,
      the total population of microtubule-associated protein 1B is present in the
      entire growth cone. Here we demonstrate that inhibition of cyclin-dependent
      kinase 5 (Cdk5) results in loss of mab1E11 binding whereas inhibition of glycogen
      synthase kinase 3 has no such effect, revealing that mab1E11 recognizes a Cdk5
      phosphorylation site on type-1 phosphorylated form of microtubule-associated
      protein 1B. We moreover show that kinase Cdk5 as well as its activator P35 is
      present in retinal ganglion cells in the early developing chick embryo retina and
      enriched in their extending axons. Cdk5 and P35 are concentrated in the youngest,
      distal axon region and the growth cone as also seen for Cdk5-phosphorylated type
      1 phosphorylated form of microtubule-associated protein 1B. Inhibition of Cdk5 by
      antibodies or inhibitor Roscovitine results in growth cone collapse and axon
      retraction and prevents substantial axon outgrowth. In contrast, glycogen
      synthase kinase 3 inhibition causes only a transient axon retraction which is
      soon recovered and allows for axon formation. In growth cones induced to turn at
      substrate borders, where stable and instable parts of the growth cone are clearly
      defined, Cdk5 is present in the entire growth cone. P35, in contrast, is
      restricted to the stable parts of the growth cone, which do not collapse but
      instead transform into new distal axon. The local presence of Cdk5-phosphorylated
      type-1 phosphorylated form of microtubule-associated protein 1B in stabilized
      growth cone areas can be therefore attributed to the local activation of Cdk5 by
      P35 in these regions. Together our data demonstrate a crucial role of Cdk5 and
      its activator P35 in elongation and maintenance of axons as well as for stability
      and steering of their growth cones.

PMID- 15964698
TI  - Evidence for neurogenesis within the white matter beneath the temporal neocortex
      of the adult rat brain.
AB  - Persistent neuron production in the adult CNS (adult neurogenesis) has been
      implicated in various brain functions such as learning/memory and mood control.
      Despite the widespread occurrence of neural stem/progenitor cells, active adult
      neurogenesis has been established only in two restricted regions. We explored in
      this study a previously overlooked neurogenic region in the adult rat brain and
      detected the evidence of neuron production within the subcortical white matter.
      Dividing Pax6- and Olig2-positive neural progenitor cells continually gave rise
      to doublecortin-positive new neurons in this region. However, the vast majority
      of newborn neurons were lost within a week of their birth. Accumulated apoptotic
      cells indicated the ongoing cell death in this area. In addition to providing the
      evidence of newborn cell migration to the hippocampus, these results suggest that
      cell genesis, death, and migration persist in a restricted subregion of the adult
      white matter.

PMID- 15964699
TI  - Molecular interactions of the type 1 human immunodeficiency virus transregulatory
      protein Tat with N-methyl-d-aspartate receptor subunits.
AB  - We investigated the effect of type 1 human immunodeficiency virus (HIV-1)
      regulatory protein Tat on N-methyl-d-aspartate (NMDA) receptors expressed in
      Xenopus oocytes by voltage-clamp recording and its role in NMDA-mediated
      neurotoxicity using cultured rat hippocampal neurons. Tat (0.01-1muM) potentiated
      NMDA-induced currents of recombinant NMDA receptors. However, in the presence of
      Zn(2+), the potentiating effect of Tat was much more pronounced, indicating an
      additional Zn(2+)-related effect on NMDA receptors. Consistently, Tat potentiated
      currents of the particularly Zn(2+)-sensitive NR1/NR2A NMDA receptor with a
      higher efficacy, whereas currents from a Zn(2+)-insensitive mutant were only
      marginally augmented. In addition, chemical-modified Tat, deficient for metal
      binding, did not reverse Zn(2+)-mediated inhibition of NMDA responses,
      demonstrating that Tat disinhibits NMDA receptors from Zn(2+)-mediated antagonism
      by complexing the cation. We therefore investigated the interplay of Tat and
      Zn(2+) in NMDA-mediated neurotoxicity using cultures of rat hippocampal neurons.
      Zn(2+) exhibited a prominent rescuing effect when added together with the
      excitotoxicant NMDA, which could be reverted by the Zn(2+)-chelator tricine.
      Similar to tricine, Tat enhanced NMDA-mediated neurotoxicity in the presence of
      neuroprotective Zn(2+) concentrations. Double-staining with antibodies against
      Tat and the NR1 subunit of the NMDA receptor revealed partial colocalization of
      the immunoreactivities in membrane patches of hippocampal neurons, supporting the
      idea of a direct interplay between Tat and glutamatergic transmission. We
      therefore propose that release of Zn(2+)-mediated inhibition of NMDA receptors by
      HIV-1 Tat contributes to the neurotoxic effect of glutamate and may participate
      in the pathogenesis of AIDS-associated dementia.

PMID- 15964700
TI  - Bilateral control of brain activity by dopamine D1 receptors: evidence from
      induction patterns of regulator of G protein signaling 2 and c-fos mRNA in D1
      challenged hemiparkinsonian rats.
AB  - Recent reports show that striatal dopamine D1-type receptors from one side of the
      normal rat brain can control brain activity (as measured by c-fos induction) on
      both sides of the brain. However, this phenomenon has not yet been studied in the
      presence of sensitized dopamine D1-type receptors. Here we address this issue by
      investigating the extent to which dopamine D1-type receptors control brain
      activation in rats with unilaterally sensitized dopamine D1-type receptors. Gene
      induction assays were used to identify activated regions from midbrain to
      forebrain in unilaterally 6-hydroxydopamine lesioned (hemiparkinsonian) rats
      challenged with the full dopamine D1-type agonist SKF82958 (3 mg/kg, 0.5 and 2
      h). The genes used are c-fos, the proven neuronal activity marker, and Regulator
      of G protein Signaling 2, a gene we propose as a marker of signaling homeostasis.
      SKF82958-mediated induction of both genes is greatly enhanced in hemiparkinsonian
      rats compared with shams, in both the lesioned and the intact hemisphere. For
      example, in the denervated caudate-putamen at 2 h postinjection, this enhancement
      is more than 80-fold for c-fos and up to 20-fold for Regulator of G protein
      Signaling 2; for the intact side this is 35-fold for c-fos and 27-fold for
      Regulator of G protein Signaling 2. Cortical induction of c-fos and Regulator of
      G protein Signaling 2 was generalized to most neocortical regions and was
      essentially equivalent in both the denervated and intact hemispheres.
      Interestingly, hippocampal structures also showed strong bilateral induction of
      both genes. This overall pattern of brain activation can be accounted for by the
      basal-ganglia thalamocortical and hippocampal circuits which both contain
      hemisphere-crossing connections and which can be initially activated in the
      lesioned hemisphere. Some regions, such as the intact striatum or the CA1 region,
      showed relatively low c-fos induction and relatively high Regulator of G protein
      Signaling 2 induction, possibly indicating that these regions are engaged in
      unusually strong signaling regulation activities. Our results show that, besides
      basal ganglia-thalamocortical circuits, dopamine D1-type-mediated brain
      activation in hemiparkinsonian rats also involves hippocampal circuits.

PMID- 15964701
TI  - Cell death or survival: molecular and connectional conditions for olivocochlear
      neurons after axotomy.
AB  - We aimed to determine whether rat olivocochlear neurons survive axotomy inflicted
      through cochlear ablation, or if they degenerate. To estimate their intrinsic
      potential for axonal regeneration, we investigated the expression of the
      transcription factor c-Jun and the growth-associated protein-43 (GAP43). Axonal
      tracing studies based on application of Fast Blue into the cochlea and calcitonin
      gene-related peptide immunostaining revealed that many, but not all, lateral
      olivocochlear neurons in the ipsilateral lateral superior olive degenerated upon
      cochleotomy. A decrease of their number was noticed 2 weeks after the lesion, and
      2 months postoperative the population was reduced to approximately one quarter
      (27-29%) of its original size. No further reduction took place at longer survival
      times up to 1 year. Most or all shell neurons and medial olivocochlear neurons
      survived axotomy. Following cochleotomy, 56-60% of the lateral olivocochlear
      neurons in the ipsilateral lateral superior olive were found to co-express c-Jun
      and GAP43. Only a small number of shell and medial olivocochlear neurons up
      regulated c-Jun expression, and only a small number of shell neurons expressed
      GAP43. Up-regulation of c-Jun and GAP43 in lateral olivocochlear neurons upon
      axotomy suggests that they have an intrinsic potential to regenerate after
      axotomy, but cell counts based on the markers Fast Blue and calcitonin gene
      related peptide indicate that this potential cannot be exploited and degeneration
      is induced instead. The survival of one quarter of the axotomized lateral
      olivocochlear neurons and of all, or almost all, shell and medial olivocochlear
      neurons appeared to depend on connections of these cells to other regions than
      the cochlea by means of axon collaterals, which remained intact after
      cochleotomy.

PMID- 15964702
TI  - Expression of estrogen receptor alpha exon-deleted mRNA variants in the human and
      non-human primate frontal cortex.
AB  - Although estrogen receptor alpha (ERalpha) mRNA has been detected in the primate
      frontal cortex, the types of ERalpha transcripts expressed, including exon
      deleted variants (Delta), have not been determined in the monkey or human frontal
      cortex. Because the types of ERalpha mRNA expressed in brain could define
      neuronal responses to estrogens, we examined the transcript pool of ERalpha mRNAs
      expressed in normal adult and developing human and macaque frontal cortex. We
      reverse transcribed total RNA from the postmortem frontal cortex of 29 normal
      adult humans, 12 rhesus macaques, and 19 people ranging from infants to adults
      and employed two rounds of nested polymerase chain reaction (PCR) to generate
      ERalpha products spanning the coding domain. In a third nested PCR, we used
      primers specific for novel sequences of exon-exon junctions created when whole
      exons are missing. By sequencing PCR products, we detected 60 instances of 12
      distinct DeltaERalpha mRNAs in adult humans and 94 instances of 13 distinct
      DeltaERalpha mRNAs in monkeys in differing patterns from one individual to
      another. In adult humans, 83% of individuals expressed at least 1 DeltaERalpha
      mRNA variant, and 100% of the monkeys expressed at least 1 DeltaERalpha mRNA
      variant. The single Delta2, Delta5, and Delta7 variants were frequently expressed
      in both human and monkey frontal cortex, Delta3 variants were rare in both
      species, and Delta6 variants were more frequently expressed in monkeys. In both
      species, we detected double, triple and quadruple Deltas, but these were less
      common than single Deltas. The pattern of human variant expression did not appear
      to change dramatically as a function of age. These findings imply the potential
      to produce different ERalpha proteins in frontal cortex, possibly with altered
      structure and function which may have physiological relevance for gene
      transcription by virtue of altered functional interactions with each other, other
      steroid hormone receptors, and genomic DNA.

PMID- 15964703
TI  - Ability of a new oral nicotine substitute to reduce smoking urge in moderate
      smokers.
AB  - The aim of this study was to assess the effectiveness of a new nicotine lozenge (
      Nicopass 1.5 mg) in reducing smoking urge after an overnight abstinence. Twenty
      four moderate smokers participated in a randomized, double-blind, placebo
      controlled, 2-period crossover trial. The results showed that 1.5 mg-nicotine
      lozenge is superior to placebo in reducing smoking urge (p = 0.0001). In
      addition, nicotine lozenge, but not placebo, significantly improved vigilance and
      psychomotor performances (p < 0.05) and displayed a cardiac chronotropic effect.
      Thus, the 1.5-mg nicotine lozenge appears as an effective aid to alleviate acute
      tobacco withdrawal symptoms in moderate smokers.

PMID- 15964704
TI  - Decreased depression in marijuana users.
AB  - Over 4400 adult internet users completed The Center for Epidemiologic Studies
      Depression scale and measures of marijuana use. We employed an internet survey in
      an effort to recruit the most depressed and marijuana-involved participants,
      including those who might prove unwilling to travel to the laboratory or discuss
      drug use on the phone or in person. We compared those who consumed marijuana
      daily, once a week or less, or never in their lives. Despite comparable ranges of
      scores on all depression subscales, those who used once per week or less had less
      depressed mood, more positive affect, and fewer somatic complaints than non
      users. Daily users reported less depressed mood and more positive affect than non
      users. The three groups did not differ on interpersonal symptoms. Separate
      analyses for medical vs. recreational users demonstrated that medical users
      reported more depressed mood and more somatic complaints than recreational users,
      suggesting that medical conditions clearly contribute to depression scores and
      should be considered in studies of marijuana and depression. These data suggest
      that adults apparently do not increase their risk for depression by using
      marijuana.

PMID- 15964705
TI  - FDG-PET in the prediction of pathologic response after neoadjuvant
      chemoradiotherapy in locally advanced, resectable esophageal cancer.
AB  - PURPOSE: To assess the efficacy of 18Fluorodeoxyglucose-positron emission
      tomography (FDG-PET) for predicting a pathologic response in locally advanced
      esophageal cancer after neoadjuvant chemoradiotherapy. METHODS AND MATERIALS: All
      enrolled patients were treated with neoadjuvant chemoradiotherapy followed by
      esophagectomy and underwent two FDG-PET scans, before and after neoadjuvant
      chemoradiotherapy. We compared the results of the preoperative FDG-PET scans with
      the pathologic results. RESULTS: From July 2001 to July 2004, 32 patients (29 men
      and 3 women) were enrolled in this study. Pathologic complete response (pCR) in
      the esophagus was achieved in 21 of 32 patients (66%). The sensitivity,
      specificity, positive predictive value (PPV), and negative predictive value (NPV)
      in the primary tumors of the preoperative FDG-PET were 27%, 95%, 75%, and 71%,
      respectively. In regional lymph nodes, these values were 16%, 98%, 36%, and 93%,
      respectively. The mean standardized uptake value (SUV) of primary tumors was
      initially 5.6 +/- 3.6 and changed to 1.5 +/- 1.3 after neoadjuvant
      chemoradiotherapy (p < 0.05). If analysis of metabolic response (SUV decrease,
      DeltaSUV) was limited to initially highly metabolic primary tumors (SUV > or
      =4.0), pathologic response was correlated with metabolic response (p = 0.006).
      CONCLUSIONS: This study suggested that the pathologic response of an initially
      highly metabolic tumor after neoadjuvant chemoradiotherapy could be correlated
      with the metabolic response, and FDG-PET can provide additional information on
      tumor response to chemoradiotherapy.

PMID- 15964706
TI  - Lack of benefit of pelvic radiation in prostate cancer patients with a high risk
      of positive pelvic lymph nodes treated with high-dose radiation.
AB  - PURPOSE: The use of pelvic radiation for patients with a high risk of lymph node
      (LN) metastasis (>15%) remains controversial. We reviewed the data at three
      institutions treating patients with a combination of external-beam radiation
      therapy and high-dose-rate brachytherapy to address the prognostic implications
      of the use of the Roach formula and the benefit of pelvic treatment. METHODS AND
      MATERIALS: From 1986 to 2003, 1,491 patients were treated with external-beam
      radiation therapy and high-dose-rate brachytherapy. The Roach formula [2/3
      prostate-specific antigen + (Gleason score -6) x 10] could be calculated for
      1,357 patients. Group I consisted of patients having a risk of positive LN < or =
      15% (n = 761), Group II had a risk >15% and < or = 30% (n = 422), and Group III
      had a risk of LN disease >30% (n = 174). A >15% risk of having positive LN was
      found in 596 patients and was used to determine the benefit of pelvic radiation.
      The pelvis was treated at two of the cancer centers (n = 312), whereas at the
      third center (n = 284) radiation therapy was delivered to the prostate and
      seminal vesicles alone. Average biologic effective dose was > or = 100 Gy
      (alphabeta = 1.2). Biochemical failure was as per the American Society for
      Therapeutic Radiology and Oncology definition. Statistics included the log-rank
      test as well as Cox univariate and multivariate analysis. RESULTS: For all 596
      patients with a positive LN risk >15%, median follow-up was 4.3 years, with a
      mean of 4.8 years. For all cases, median follow-up was 4 years and mean follow-up
      was 4.4 years. Five-year results for the three groups based on their risk of
      positive LN were significantly different in terms of biochemical failure (p <
      0.001), clinical control (p < 0.001), disease-free survival excluding biochemical
      failure (p < 0.001), cause-specific survival (p < 0.001), and overall survival (p
      < 0.001). For all patients with a risk of positive LN >15% (n = 596), Group II
      (>15-30% risk), or Group III (>30% risk), no benefit was seen in the 5-year rates
      of clinical failure, cause-specific survival, or overall survival with pelvic
      radiation. In the Cox multivariate analysis for cause-specific survival, Gleason
      score (p = 0.009, hazard ratio [HR] 3.1), T stage (p = 0.03, HR 1.8), and year of
      treatment (p = 0.05, HR 1.1) were significant. A log-rank test for cause-specific
      survival for all patients (n = 577) by the use of pelvic radiation was not
      significant (p = 0.99) accounting for high-dose-rate brachytherapy dose,
      neoadjuvant hormones, Gleason score, prostate-specific antigen, T stage, and year
      of treatment as covariates. CONCLUSIONS: The use of the Roach formula to stratify
      patients for clinical and biochemical outcomes is excellent. Pelvic radiation
      added to high prostate radiation doses did not show a clinical benefit for
      patients at a high risk of pelvic LN disease (>15%) selected using the Roach
      formula.

PMID- 15964707
TI  - Quality of life of patients after permanent prostate brachytherapy in relation to
      dosimetry.
AB  - PURPOSE: To investigate changes in quality of life (QoL) after permanent prostate
      brachytherapy and to correlate these changes with postimplant dosimetry based on
      magnetic resonance (MR) images. METHODS AND MATERIALS: For this study, 127
      patients with low-stage prostate cancer and treated with brachytherapy received a
      QoL questionnaire at five time points: before treatment and at 4 weeks, 6 months,
      1 year, and 2 years after treatment. The questionnaire included the RAND-36
      generic health survey, the cancer-specific European Organization for Research and
      Treatment of Cancer (EORTC) core questionnaire, the tumor-specific EORTC prostate
      cancer module, and the American Urological Association symptom index. Postimplant
      dosimetry was based on registered T1 spin echo transversal, T2 turbo spin echo
      transversal, and T2 turbo spin echo sagittal MR images and CT images taken 4
      weeks after implantation of the iodine-125 seeds. Calculated parameters were
      prostate volume, prostate volume receiving 100% (V100) and 150% (V150) dose, dose
      to 90% of the prostate volume (D90), maximum dose in 1-, 2-, and 5-cm3 rectum
      volume, distance between prostate and anterior rectum wall, and the maximum dose
      in 1%, 2%, and 5% urethra volume. Analysis of variance for repeated measures was
      used for comparison of the means of all variables in the different
      questionnaires. Linear regression analysis (stepwise) was used to investigate the
      correlations between QoL parameters and dosimetry parameters. RESULTS: On
      average, only the QoL at 4 weeks after implant was significantly different from
      (worse than) the QoL at the other time points. Regression analysis showed a
      significant correlation between changes in bowel problems and the maximum dose in
      2-cm3 rectum volume, between changes in urinary symptoms and prostate volume, and
      between changes in urinary problems and the D90 value of the prostate.
      CONCLUSIONS: The QoL for patients with permanent prostate implants was worse in
      the first months after treatment but returned to baseline values 1 year after
      implant. Significant correlations were found between dose distribution and QoL.

PMID- 15964708
TI  - A comparison of mean parotid gland dose with measures of parotid gland function
      after radiotherapy for head-and-neck cancer: implications for future trials.
AB  - PURPOSE: To determine the most adequate parameter to measure the consequences of
      reducing the parotid gland dose. METHODS AND MATERIALS: One hundred eight
      patients treated with radiotherapy for various malignancies of the head and neck
      were prospectively evaluated using three methods. Parotid gland function was
      objectively determined by measuring stimulated parotid flow using Lashley cups
      and scintigraphy. To assess xerostomia-related quality of life, the head-and-neck
      cancer module European Organization for Research and Treatment of Cancer QLQ
      (Quality of Life Questionnaire) H&N35 was used. Measurements took place before
      radiotherapy and 6 weeks and 12 months after the completion of radiotherapy.
      Complication was defined for each method using cutoff values. The correlation
      between these complications and the mean parotid gland dose was investigated to
      find the best measure for parotid gland function. RESULTS: For both flow and
      scintigraphy data, the best definition for objective parotid gland toxicity
      seemed to be reduction of stimulated parotid flow to < or =25% of the
      preradiotherapy flow. Of all the subjective variables, only the single item dry
      mouth 6 weeks after radiotherapy was found to be significant. The best
      correlation with the mean parotid gland dose was found for the stimulated flow
      measurements. The predictive ability was the highest for the time point 1 year
      after radiotherapy. Subjective findings did not correlate with the mean parotid
      dose. CONCLUSIONS: Stimulated flow measurements using Lashley cups, with a
      complication defined as flow < or =25% of the preradiotherapy output, correlated
      best with the mean parotid gland dose. When reduction of the mean dose to the
      parotid gland is intended, the stimulated flow measurement is the best method for
      evaluating parotid gland function.

PMID- 15964709
TI  - Cognitive function after radiotherapy for supratentorial low-grade glioma: a
      North Central Cancer Treatment Group prospective study.
AB  - PURPOSE: To evaluate the effects of cranial radiotherapy (RT) on cognitive
      function in patients with supratentorial low-grade glioma. METHODS AND MATERIALS:
      Twenty adult patients with supratentorial low-grade glioma were treated with 50.4
      Gy (10 patients) or 64.8 Gy (10 patients) localized RT. The patients then were
      evaluated with an extensive battery of psychometric tests at baseline (before RT)
      and at approximately 18-month intervals for as long as 5 years after completing
      RT. To allow patients to serve as their own controls, cognitive performance was
      evaluated as change in scores over time. All patients underwent at least two
      evaluations. RESULTS: Baseline test scores were below average compared with age
      specific norms. At the second evaluation, the groups' mean test scores were
      higher than their initial performances on all psychometric measures, although the
      improvement was not statistically significant. No changes in cognitive
      performance were seen during the evaluation period when test scores were analyzed
      by age, treatment, tumor location, tumor type, or extent of resection.
      CONCLUSIONS: Cognitive function was stable after RT in these patients evaluated
      prospectively during 3 years of follow-up. Slight improvements in some cognitive
      areas are consistent with practice effects attributable to increased familiarity
      with test procedures and content.

PMID- 15964710
TI  - Intraoperative radiation therapy in recurrent ovarian cancer.
AB  - PURPOSE: To evaluate disease outcomes and complications in patients with
      recurrent ovarian cancer treated with cytoreductive surgery and intraoperative
      radiation therapy (IORT). METHODS AND MATERIALS: A retrospective study of 24
      consecutive patients with ovarian carcinoma who underwent secondary cytoreduction
      and intraoperative radiation therapy at our institution between 1994 and 2002 was
      conducted. After optimal cytoreductive surgery, IORT was delivered with
      orthovoltage X-rays (200 kVp) using individually sized and beveled cone
      applications. Outcomes measures were local control of disease, progression-free
      interval, overall survival, and treatment-related complications. RESULTS: Of
      these 24 patients, 22 were available for follow-up analysis. Additional treatment
      at the time of and after IORT included whole abdominopelvic radiation, 9; pelvic
      or locoregional radiation, 5; chemotherapy, 6; and no adjuvant treatment, 2. IORT
      doses ranged from 9-14 Gy (median, 12 Gy). The anatomic sites treated were pelvis
      (sidewalls, vaginal cuff, presacral area, anterior pubis), para-aortic and
      paracaval lymph node beds, inguinal region, or porta hepatitis. At a median
      follow-up of 24 months, 5 patients remain free of disease, whereas 17 patients
      have recurred, of whom 4 are alive with disease and 13 died from disease. Five
      patients recurred within the radiation fields for a locoregional relapse rate of
      32% and 12 patients recurred at distant sites with a median time to recurrence of
      13.7 months. Five-year overall survival was 22% with a median survival of 26
      months from time of IORT. Nine patients (41%) experienced Grade 3 toxicities from
      their treatments. CONCLUSION: In carefully selected patients with locally
      recurrent ovarian cancer, combined IORT and tumor reductive surgery is reasonably
      tolerated and may contribute to achieving local control and disease palliation.

PMID- 15964711
TI  - Effect of isolated fractions of Barleria prionitis root methanolic extract on
      reproductive function of male rats: preliminary study.
AB  - Male rats treated with 100 mg/kg for 60 days of isolated fractions of the
      Barleria prionitis root methanolic extract (Fr. I and Fr. II) showed a
      significant reduction on spermatogenesis without affecting general body
      metabolism. Sperm motility as well density in cauda epididymides was reduced
      significantly. The fertility was decreased by 33.4% in Fr. I and 100% in Fr. II
      treated rats. The blood parameters were within the normal range. Total protein,
      glycogen and sialic acid contents of testes were reduced after the plant
      fractions treatment. Seminal vesicular fructose was decreased significantly after
      the treatment. The population of various spermatogenic cells such as primary
      spermatocytes, secondary spermatocytes and round spermatids were declined
      significantly in Fr. II treatment groups whereas in Fr. I treated animals
      preleptotene spermatocyte and spermatid number was decreased. There was no
      significant change in the number of Sertoli cells and spermatogonia in any of the
      treatment group.

PMID- 15964712
TI  - Antimicrobial and cytotoxic constituents from the seeds of Annona squamosa.
AB  - Annotemoyin-1, Annotemoyin-2, squamocin and cholesteryl glucopyranoside were
      isolated from the seeds of Annona squamosa. These compounds and plant extracts
      showed remarkable antimicrobial and cytotoxic activities.

PMID- 15964713
TI  - [Molecular characterization of invasive Haemophilus influenzae strains isolated
      in Tunisia].
AB  - We reported a molecular characterization of 25 Haemophilus influenzae strains
      derived from cases of meningitis and sepsis in children aged less than five years
      hospitalized in pediatric wards from three hospitals in the Sahel area (Tunisia)
      during the period 1997-2002. These strains were biotyped and subjected to a
      capsular typing by Slide agglutination serotyping and Polymerase Chain Reaction
      (PCR). The genetic polymorphism of these strains was also studied in Arbitrarily
      Primed Polymerase Chain Reaction (AP-PCR) with two sets of primers: RAP IV and
      217 delta(2) as in Pulsed Field Gel Electrophoresis after digestion of the total
      DNA with the restriction enzyme SmaI (PFGE SmaI). Nineteen strains among 25 (76%)
      were of biotype I. The bexA gene was highlighted in 13 strains (52%) and in all
      the cases it was of the type b. Twelve strains (48%) were shown to be
      unencapsulated by PCR. AP-PCR RAP IV (23 genotypes/25 with a discrimination index
      ID=0.993) had shown nearly the same discriminatory power than PFGE (20
      genotypes/21 strains with a discrimination index ID=0.995). We thus note, how
      capsular typing by PCR is more sensitive than slide agglutination serotyping. We
      also note the genetic diversity of the invasive strains isolated with a
      remarkable presence of non typable strains. AP PCR seems to be an alternative of
      choice for the epidemiologic follow-up of the Haemophilus influenzae invasive
      infections.

PMID- 15964714
TI  - Factors associated with methadone maintenance therapy use among a cohort of
      polysubstance using injection drug users in Vancouver.
AB  - We identified methadone maintenance therapy (MMT) use during follow-up interviews
      and examined associations between MMT use and socio-demographic and drug-related
      variables using generalized estimating equations (GEE). Of the 1587 participants
      recruited into this cohort, 170 (11%) were enrolled in MMT at baseline and
      additional 498 (31%) initiated MMT during follow-up. Of those ever enrolled in
      MMT, 406 (61%) ceased MMT and re-initiated MMT on more than one occasion. The
      median treatment duration was 14.4 months. Factors that were negatively and
      significantly associated with MMT use in multivariate analyses included:
      Aboriginal ethnicity (adjusted odds ratio [AOR] = 0.40); recent incarceration
      (AOR = 0.79); sex trade involvement (AOR = 0.87); syringe lending (AOR = 0.72);
      heroin injection (AOR = 0.64), whereas female gender (AOR = 2.47), HIV positivity
      (AOR = 1.57), and crack cocaine smoking (AOR = 1.23) were positively and
      significantly associated with being on MMT. Unstable housing, syringe borrowing,
      non-fatal overdose, cocaine injection, and residence in Vancouver's Downtown
      Eastside were not associated with MMT use in multivariate analyses. Our study
      demonstrates high rates of initiation of and retention in MMT among local IDUs.
      While the use of MMT was associated with reductions in heroin use and HIV risk
      behavior, barriers to Aboriginal IDUs were evident, and the association with
      increased crack cocaine use deserves further study.

PMID- 15964715
TI  - Association between psychiatric disorders and smoking stages among Latino
      adolescents.
AB  - OBJECTIVE: We examined the prevalence of smoking behaviors and their association
      with psychiatric disorders within a representative sample of youth from Puerto
      Rico. METHOD: A complex sampling design was used and analyses were conducted to
      account for the unequal selection probability, stratification and clustering. All
      analyses were weighted back to the population from which they were drawn.
      Psychiatric and substance use disorders were assessed using the parent and youth
      versions of the Diagnostic Interview Schedule for Children, Version 4.0 (DISC
      IV). RESULTS: After controlling for other comorbidity, major depression and
      oppositional defiant disorder were significantly associated with nicotine
      dependence, rather than with lower levels of use. In contrast, conduct disorder
      was generally associated with lower levels of use rather than with nicotine
      dependence. As expected, the alcohol and drug use disorders demonstrated some of
      the strongest associations with individual smoking stages. CONCLUSIONS: By
      examining psychiatric correlates of smoking stages within an island-wide sample
      of adolescents, the present study highlights those disorders that may play a role
      in the development and/or persistence of smoking behavior in Puerto Rico and
      further clarifies the appropriate targets for smoking intervention conducted in
      community settings.

PMID- 15964716
TI  - Bioaugmentation potential of a vinyl chloride-assimilating Mycobacterium sp.,
      isolated from a chloroethene-contaminated aquifer.
AB  - An aerobic bacterium, Mycobacterium sp. strain TRW-2 that assimilated vinyl
      chloride (VC) or ethene (ETH) as the sole carbon source was isolated from a
      chloroethene-degrading enrichment culture. The strain TRW-2 also degraded cis
      dichloroethene (cis-DCE) in mineral salts medium, but only when VC was present as
      the primary carbon source. However, no degradation of trans-dichloroethene or
      trichloroethene occurred in either the presence or absence of added VC. The
      measured growth yield values were 6.53 and 14.1g protein/mol of VC and ETH
      utilized, respectively. Inoculation by strain TRW-2 in microcosms prepared with
      aquifer samples resulted in rapid degradation of VC, whereas native bacteria
      degraded negligible amounts of VC within the same time period, thus suggesting
      bioaugmentation potential of the isolate. Phylogenetic analysis of the 16S rDNA
      sequence of the isolate revealed 98% sequence similarity to the members of the
      genus Mycobacterium. In summary, the isolate's ability to degrade VC, cis-DCE,
      and ETH and also its ability to survive and degrade VC in the presence of other
      microorganisms is relevant to the remediation of VC-impacted aquifers.

PMID- 15964717
TI  - Fine affinity discrimination by normalized fluorescence activated cell sorting in
      staphylococcal surface display.
AB  - We have investigated a staphylococcal surface display system for its potential
      future use as a protein library display system in combinatorial biochemistry.
      Efficient affinity-based selections require a system capable of fine affinity
      discrimination of closely related binders to minimize the loss of potentially
      improved variants. In this study, a significant breakthrough was achieved to
      avoid biases due to potential cell-to-cell variations in surface expression
      levels, since it was found that a generic protein tag, present within the
      displayed recombinant surface proteins on the cells, could be successfully
      employed to obtain normalization of the target-binding signal. Four mutated
      variants of a staphylococcal protein A domain with different affinity to human
      IgG were successfully expressed on the surface of recombinant Staphylococcus
      carnosus cells. The system was evaluated for affinity-based cell sorting
      experiments, where cell-displayed protein A domains with an 8-fold difference in
      target affinity were mixed at a ratio of 1:1000 and sorted using FACS. Enrichment
      factors around 140-fold were obtained from a single round of sorting under normal
      library sorting conditions when the top 0.1% fraction having the highest antigen
      binding to surface expression level ratio was sorted. The results demonstrate
      that the system would have a potential as a selection system in protein library
      display applications, and the normalization strategy should indeed make it
      possible to achieve fine affinity discriminations in future library selections.

PMID- 15964718
TI  - Rapid and quantitative detection of blood Serratia marcescens by a real-time PCR
      assay: its clinical application and evaluation in a mouse infection model.
AB  - Large-scale nosocomial outbreaks of Serratia marcescens septicaemia in Japan have
      had a fatality rate of 20-60% within 48 h. As a countermeasure, a real-time PCR
      assay was constructed for the rapid diagnosis of S. marcescens septicaemia. This
      assay indeed detected S. marcescens in clinical blood specimens (at ca. 10(2)CFU
      ml(-1)), at a frequency of 0.5% in suspected cases of septicaemia. In mice, the
      assay provided estimates of blood S. marcescens levels at various infectious
      stages: namely, 10(7) to 10(8)CFU ml(-1) at a fatal stage (resulting in 100%
      death), 10(4)-10(5)CFU ml(-1) at a moderately fatal stage (resulting in 50% or
      more death), and <10(3)CFU ml(-1) at a mild stage (resulting in 100% survival),
      consistent with actual CFU measurements. Blood bacterial levels could be an
      important clinical marker that reflects the severity of septicaemia. The
      simultaneous detection of S. marcescens and the carbapenem resistance gene was
      also demonstrated.

PMID- 15964719
TI  - Molecular cloning and characterization of a novel soybean gene encoding a leucine
      zipper-like protein induced to salt stress.
AB  - To understand molecular responses to salt stress in soybean (Glycine max [L.]
      Merr.), we identified 106 salt-inducible soybean genes that expressed
      differentially at 72 h after 100 mM NaCl treatment using the cDNA-amplified
      fragment length polymorphism (AFLP) method. The genes were designated as G. max
      Transcript-Derived Fragments (GmTDFs). Among these genes, we characterized a
      soybean gene GmTDF-5 that encoded an unknown protein of 367 amino acids. The
      GmTDF-5 protein was a putative cytosolic protein with two leucine-zipper motifs
      at the N-terminal and was calculated as 40.7 kDa. Southern blot analysis
      indicated that GmTDF-5 presents as an intron-less single gene on soybean genome
      and possibly distributes narrowly throughout the higher plants. By 100 mM NaCl
      treatment, the gene expression of GmTDF-5 was induced in the stem and lower
      expanded leaf, and the amount of mRNA increased 5.1- and 2.0-fold up to 72 h,
      respectively. Interestingly, GmTDF-5 expression in the upper-leaf appeared
      dramatically with 10.0-fold increase at 72 h after the salt stress, but not until
      48 h. Hyperosmotic pressure (mannitol treatment) and dehydration also caused the
      increases similar to NaCl treatment in the levels of GmTDF-5 expression. These
      results suggest that GmTDF-5 might be a novel cytosolic leucine-zipper-like
      protein functioning in mature organs of soybean shoot against water-potential
      changes.

PMID- 15964720
TI  - Prevalence and risk-factor analysis of Shiga toxigenic Escherichia coli in faecal
      samples of organically and conventionally farmed dairy cattle.
AB  - Cattle are a natural reservoir for Shiga toxigenic Escherichia coli (STEC),
      however, no data are available on the prevalence and their possible association
      with organic or conventional farming practices. We have therefore studied the
      prevalence of STEC and specifically O157:H7 in Swiss dairy cattle by collecting
      faeces from approximately 500 cows from 60 farms with organic production (OP) and
      60 farms with integrated (conventional) production (IP). IP farms were matched to
      OP farms and were comparable in terms of community, agricultural zone, and number
      of cows per farm. E. coli were grown overnight in an enrichment medium, followed
      by DNA isolation and PCR analysis using specific TaqMan assays. STEC were
      detected in all farms and O157:H7 were present in 25% of OP farms and 17% of IP
      farms. STEC were detected in 58% and O157:H7 were evidenced in 4.6% of individual
      faeces. Multivariate statistical analyses of over 250 parameters revealed several
      risk-factors for the presence of STEC and O157:H7. Risk-factors were mainly
      related to the potential of cross-contamination of feeds and cross-infection of
      cows, and age of the animals. In general, no significant differences between the
      two farm types concerning prevalence or risk for carrying STEC or O157:H7 were
      observed. Because the incidence of human disease caused by STEC in Switzerland is
      low, the risk that people to get infected appears to be small despite a
      relatively high prevalence in cattle. Nevertheless, control and prevention
      practices are indicated to avoid contamination of animal products.

PMID- 15964721
TI  - First partial characterisation of small ruminant lentiviruses from Greece.
AB  - Small ruminant lentivirus (SRLV) infections are widespread in Greece, but SRLVs
      have never been isolated and characterized. In this study, we present the
      sequence of a 574-nucleotide (191-amino acid) region of the gag gene of SRLV
      strains from four sheep and one goat from a single geographic area of Greece. All
      five sequences appeared to be closely related at both nucleotide (2.1-14.2%
      variation) and deduced amino acid (1.6-4.2% variation) level. Greek SRLV strains
      were closer to ovine prototypic strains (average divergence 16.8%) than to the
      caprine strain CAEV-Co (21% divergence). By amino acid composition, the Greek
      SRLVs were on the average more than twice as distant from CAEV-Co as from other
      ovine strains. Phylogenetic analysis suggested that Greek strains segregate into
      a unique group, separate from, but related to, other ovine prototype sequences.

PMID- 15964722
TI  - Role of gut macrophages in mice orally contaminated with scrapie or BSE.
AB  - While there is a growing consensus on the understanding of the propagation
      pathways after oral infection of transmissible spongiform encephalopathy (TSE)
      agents and even if the central role of follicular dendritic cells is identified,
      little is known about the key players in the first steps of the infection and
      about the site of the disease development. We investigated the role of gut
      macrophages, which are capable of capturing aggregates of the prion protein. PLGA
      particles containing clodronate were designed in order to be orally administered
      and to target Peyer's patches for inducing gut-associated macrophages suicide in
      mice. Mice were subsequently infected with scrapie or BSE by the oral route. It
      was found that the efficacy of macrophage suppression in the Peyer's patches
      correlated well with an earlier appearance of PrPres in these formations and with
      a higher amount of PrPres at a later stage of the infection. Thus, the capture of
      infectious particles that have crossed the epithelial gut barrier and their
      elimination by macrophages seems to be a key event to restrict the amount of
      agent initiating the infection.

PMID- 15964723
TI  - Kinetic analysis of protein production after DNA transfection.
AB  - The production of an exogenous protein by the transfection of a plasmid DNA
      encoding the protein was kinetically analyzed, to determine the efficiency of the
      transfection. Cultured NIH3T3 or HeLa cells, and the luciferase protein were used
      as a model system in this experiment. The findings indicate that at least a
      8x10(4)- and 4x10(3)-fold molar amounts of luciferase protein was produced from
      one copy of the plasmid DNA molecule in NIH3T3 and HeLa cells, respectively. The
      rate of elimination of luciferase activity upon DNA transfection was smaller than
      that for the luciferase protein itself (k(el) for DNA transfection<k(el) for the
      luciferase protein), suggesting that a decrease in intranuclear active DNA was
      the main determinant of the elimination rate in this case. A preliminary
      pharmacokinetic model is proposed, based on the results obtained.

PMID- 15964724
TI  - Maintaining the cold chain shipping environment for Phase I clinical trial
      distribution.
AB  - The study aimed to demonstrate satisfactory inter-UK transit of cold storage
      clinical trial material. The product environment had to be maintained between 0
      and 8 degrees C throughout transit until delivery. Straightforward, low cost and
      simplified shipping arrangements were sought that would be appropriate for small
      scale Phase I clinical trial activities. A laboratory test defined an optimal
      three frozen gel pack configuration to maintain refrigerated environmental
      conditions for dummy product packs in a single type and size of insulated
      shipper. The internal environment was temperature monitored at 30-min intervals
      in all tests. Twelve Glasgow to London transits were then studied over 2 years to
      include all seasonal temperature variations. A configuration using three frozen
      gel packs and 4 h pre-chill of the transit container maintained the internal
      environment at 0-8 degrees C for up to 48 h during autumn, winter and spring. A
      modified four frozen gel pack configuration was suitable for summer transit. Thus
      cold shipment verification was successfully carried out for a small-scale
      distribution operation. It was proven that refrigerated shipping conditions could
      be maintained using a straightforward and cost effective 'passive' type system
      consisting of frozen gel packs and insulated transit containers.

PMID- 15964725
TI  - Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non
      syndromic deaf patients.
AB  - Genetically caused congenital deafness is a common trait affecting 1 in 2000
      children and it is predominantly inherited in an autosomal recessive fashion.
      Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 (delGJB6
      D13S1830) have been identified worldwide in patients with hearing impairment. The
      aim of this study was to determine the prevalence of these mutations in
      Argentina. Non-syndromic 46 probands (17 familial and 29 sporadic cases) were
      genetically evaluated. Mutations in GJB2 and/or delGJB6-D13S1830 were found in 19
      patients, accounting for 41.3% of the sample. Of the 46 patients investigated in
      this study, 12 (26.1%) were diagnosed to carry sequence variations in both
      alleles; all but one, were considered causative for hearing impairment in those
      patients. In 7 out of 46 patients (15.2%) only one mutant allele was detected. Of
      their 38 chromosomes, 71% resulted with mutations in the GJB2 gene and 11% in
      GJB6. The most frequent mutation in GJB2 (24%) was c.35delG (11% homozygous and
      13% heterozygous and compound heterozygous). In addition, 11 sequence variations
      different from c.35delG, were identified in the coding region of the GJB2 gene:
      T8M, V27I, M34T, E47X, R75W, W77R, I82M, L90P, E129K, V153I, M163V. The delGJB6
      D13S1830 mutation was found in 4 patients (9%), 3 of them associated with GJB2
      mutations, resulting in compound heterozygous for the DFNB1 locus. The present
      study demonstrates that mutations in the GJB2 gene and the delGJB6-D13S1830 are
      prevalent in the Argentinean population.

PMID- 15964726
TI  - Antipruritic effect of the single oral administration of German chamomile flower
      extract and its combined effect with antiallergic agents in ddY mice.
AB  - The single peroral administration of the ethyl acetate extract or essential oil
      of German chamomile (Matricaria recutita L.) showed remarkable antipruritic
      effects in the compound 48/80-induced itch-scratching test in ddY mice, if
      suitable vehicle was used. The ethyl acetate extract or essential oil of German
      chamomile dissolved in the vehicle of 10% ethanol, 10% Tween 80 and 80%
      physiological saline was orally administrated 2 h before pruritus provocation by
      compound 48/80 subcutaneous injection. The ethyl acetate extract or essential oil
      of German chamomile showed significant dose-dependent inhibition of the compound
      48/80-induced scratching without affecting spontaneous motor activity. The
      antipruritic effects of antihistamine H1 antagonists, oxatomide (10 mg/kg) and
      fexofenadine (10 mg/kg), were only partial in this test. However, the
      antipruritic effects of these agents were remarkably enhanced by the combined
      administration of the ethyl acetate extract of German chamomile (300 mg/kg).
      Thus, the co-medication with the ethyl acetate extract, or essential oil of
      German chamomile and antihistamines might be effective for the pruritus which
      could not be perfectly resolved alone by conventional antihistamines.

PMID- 15964727
TI  - Medicinal plants and antimicrobial activity.
AB  - In the present paper, we analyze the past, present and future of medicinal
      plants, both as potential antimicrobial crude drugs as well as a source for
      natural compounds that act as new anti-infection agents. In the past few decades,
      the search for new anti-infection agents has occupied many research groups in the
      field of ethnopharmacology. When we reviewed the number of articles published on
      the antimicrobial activity of medicinal plants in PubMed during the period
      between 1966 and 1994, we found 115; however, in the following decade between
      1995 and 2004, this number more than doubled to 307. In the studies themselves
      one finds a wide range of criteria. Many focus on determining the antimicrobial
      activity of plant extracts found in folk medicine, essential oils or isolated
      compounds such as alkaloids, flavonoids, sesquiterpene lactones, diterpenes,
      triterpenes or naphtoquinones, among others. Some of these compounds were
      isolated or obtained by bio-guided isolation after previously detecting
      antimicrobial activity on the part of the plant. A second block of studies
      focuses on the natural flora of a specific region or country; the third relevant
      group of papers is made up of specific studies of the activity of a plant or
      principle against a concrete pathological microorganism. Some general
      considerations must be established for the study of the antimicrobial activity of
      plant extracts, essential oils and the compounds isolated from them. Of utmost
      relevance is the definition of common parameters, such as plant material,
      techniques employed, growth medium and microorganisms tested.

PMID- 15964728
TI  - Country development does not presuppose the loss of forest resources for
      traditional medicine use.
AB  - There are challenges in using ethnobotany as a research technique. Foremost,
      there is a generational loss of traditional medicine knowledge and a loss of
      plant resources as raw material for medicinal use. These losses are frequently
      attributed to the development and modernization of cultures. However, recent work
      has reported that the loss of languages, a classic marker of traditional
      knowledge, does not correlate with the relative development status of a country.
      By analyzing datasets regarding the relative development status of countries and
      land use patterns, I show that the loss of natural resources for traditional
      medicine use does not correlate with the relative development status of a
      country. This work implies that with proper governance, it is possible for
      countries to develop while preserving the natural resources utilized in
      traditional medicine.

PMID- 15964729
TI  - Y-chromosome STR haplotypes in a population sample from Switzerland (Zurich
      area).
AB  - Allele frequencies and haplotypes for 12 Y-chromosome STR loci (DYS19, DYS385a/b,
      DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438 and DYS439),
      included in the PowerPlex Y multiplex kit, were determined for a Swiss population
      sample of 150 male individuals. The gene diversities for the different loci were
      in the same range as shown for other European Population samples. The haplotype
      diversity was 0.9922. Pairwise haplotype analysis showed no significant
      differences in comparison with other European Population samples.

PMID- 15964730
TI  - Population data of Y-chromosomal STRs in Russian males of the Primorye region
      population.
AB  - Data of eight Y-chromosomal STRs, the so called "minimal core set", were obtained
      from 152 unrelated males of the Primorye region of Russia. The allelic
      frequencies correspond to other European populations. The background is a
      settlement of males from the European part of Russia, Ukraine and other states
      which were included in the former western part of the Soviet Union. On the other
      hand the distribution of the most frequent haplotypes differs to the Ukraine and
      Russian population. The most frequent haplotype was obtained five times in the
      population corresponding to 3.3%. The haplotype data reported here have been
      included into the Y-STR database maintained at the Institute of Legal Medicine,
      Humboldt-University, Berlin.

PMID- 15964731
TI  - Interaction of daunomycin antibiotic with human serum albumin: investigation by
      resonant mirror biosensor technique, fluorescence spectroscopy and molecular
      modeling methods.
AB  - Daunomycin (DM) is a clinically used antitumor anthracycline antibiotic, which is
      transported primarily by human serum albumin (HSA) in the blood. Binding
      characteristics are therefore of interest for both the pharmacokinetics and
      pharmacodynamics of DM. A new optical biosensor technique based on the resonant
      mirror was used to characterize interaction of DM with HSA at different
      temperatures and the affinity constants were obtained. The HSA-DM interaction is
      exothermic with having favorable enthalpy and entropy followed by the integrated
      van't Hoff equation analysis. Fluorescence studies showed that DM has an ability
      to quench the intrinsic fluorescence of HSA through a static quenching procedure
      according to the Stern-Volmer equation and DM displays a pH-dependent binding
      affinity to HSA. Molecular modeling calculations showed that the DM binds HSA to
      a non-classical drug binding site and further analysis of the binding site of DM
      within the HSA molecule suggested that hydrophobic contacts, hydrogen bond
      formation and electrostatic interactions account for the binding of DM.

PMID- 15964732
TI  - A respiration-metabolism chamber system and a GC-MS method developed for studying
      exhalation of perfluorobutane in rats after intravenous injection of the
      ultrasound contrast agent Sonazoid.
AB  - Sonazoid is a new contrast agent for ultrasound imaging comprising an aqueous
      suspension of lipid-stabilised perfluorobutane (PFB) gas microbubbles. A
      respiration-metabolism chamber system was developed to collect exhaled air
      following intravenous administration of Sonazoid to rats. Analysis of PFB in the
      exhaled rat air was performed using a modified version of an earlier published
      method for blood samples, i.e. an automatic headspace gas chromatographic mass
      spectrometric (GC-MS) method using electron impact ionisation. The calibration
      standards were PFB diluted in air (2.5-1800 pg/ml). Perfluoropentane (PFP) was
      used as an internal standard and the MS detector was set to single ion monitoring
      of the base fragment ions of PFB (m/z 69 and 119) and PFP (m/z 69). The
      calibration curve, made by plotting the peak area ratios of PFB (m/z 69) to PFP
      (m/z 69) against the theoretical concentration of PFB, was fitted to a linear
      equation with weighting 1/y2 and found to be reproducible. The lower limit of
      quantification (LLOQ) was 2.5 pg PFB/ml. The between-day variation of the method
      was below 2.6% relative standard deviation (R.S.D.) and the within-day variation
      of the method was below 6.4% R.S.D. The accuracy of the method was evaluated and
      showed a relative error less than 5.2%. PFB was found to be stable for 14 days
      when stored in Tedlar sample bags at room temperature. An even lower detection
      limit may be obtained by using the more time-consuming process of solid-phase
      micro extraction; thus, by concentrating PFB on carboxen-PDMS fibres an LLOQ of
      0.5 pg PFB/ml was obtained. When five rats were given an i.v. bolus injection of
      Sonazoid at a dose of 8 microl microbubbles/kg a mean recovery of 96% (range, 81
      110%) was found during 24 h; more than 50% was exhaled during the first 30 min
      after injection.

PMID- 15964733
TI  - Supporting adherence and healthy lifestyles in leg ulcer patients: systematic
      development of the Lively Legs program for dermatology outpatient clinics.
AB  - OBJECTIVES: The objective of our project was to develop a lifestyle program for
      leg ulcer patients at outpatient clinics for dermatology. METHODS: We used the
      intervention-mapping (IM) framework for systematically developing theory and
      evidence based health promotion programs. We started with a needs-assessment. A
      multidisciplinary project group of health care workers and patients was involved
      in all five IM steps; formulating proximal program objectives, selecting methods
      and strategies, producing program components, planning for adoption and
      implementation and planning for evaluation. Several systematic literature reviews
      and original studies were performed to support this process. RESULTS: Social
      Cognitive Theory was selected as the main theory behind the program 'Lively Legs'
      and was combined with elements of Goal-Setting Theory, the precaution adoption
      model and motivational interviewing. The program is conducted through health
      counseling by dermatology nurses and was successfully pre-tested. Also, an
      implementation and evaluation plan were made. CONCLUSION: Intervention mapping
      helped us to succeed in developing a lifestyle program with clear goals and
      methods, operational strategies and materials and clear procedures. PRACTICE
      IMPLICATIONS: Coaching leg ulcer patients towards adherence with compression
      therapy and healthy lifestyles should be taken on without delay. Systematic
      development of lifestyle programs for other patient groups should be encouraged.

PMID- 15964734
TI  - How do the accounts of the patients on pregnancy and birth process enlighten
      medical team in terms of narrative ethics?
AB  - OBJECTIVE: The aim of this study is to evaluate the relationship between the
      patient and the physician, midwife and nurse during the process of pregnancy and
      birth, and to ascertain the importance of communication within this relationship;
      find out the experiences of patients about the communication process. METHODS:
      Three hundred eighty-eight people were interviewed about the pregnancy and birth
      process. Chi square (chi(2)) and t-tests were used for the statistical evaluation
      of the data. Forty-nine pregnant women, who were participating in any pregnancy
      training program, were asked to write down their experiences related to the
      pregnancy and birth process in a notebook. Thirty-two (65.3%) of these notebooks
      were taken back 3 months after the delivery, and these notebooks were evaluated
      within the framework of "narrative ethics" and common themes were found out in
      order to be discussed in this paper. RESULTS: It is found out that communication
      skills of doctors and midwives/nurses were of primary importance for all the
      participants. CONCLUSION: Pregnancy and birth are special processes and being
      informed is of great importance in this process. Every woman has a story to tell
      about her pregnancy and birth processes. PRACTICE IMPLICATION: These findings may
      contribute to the development of new hypotheses. Hence, similar research projects
      should be conducted, and the findings should be compared.

PMID- 15964735
TI  - Informed consent? How do primary care professionals prepare women for cervical
      smears: a qualitative study.
AB  - BACKGROUND: Cervical screening is a procedure that is mainly carried out in
      primary care, predominantly by general practitioners (GPs) and practice nurses
      (PNs). Much has been published about the effects on women of receiving an
      abnormal smear result but little has been done to investigate the preparation of
      women by primary care professionals for this. OBJECTIVE: To explore the self
      reported behaviours of GPs and PNs in preparing a woman for a cervical smear test
      and possible abnormal result. METHODS: Letters inviting respondents to
      participate were sent to selected GPs and PNs at medical student teaching
      practices in Manchester, England. Twelve GPs and 15 PNs were interviewed.
      Interviews were audiotaped and covered aspects of the cervical screening
      programme, practice protocols and explored views about consenting a woman for a
      smear test and the information giving about the possibility of an abnormal test
      result. Interviews were analysed by constant comparison and the interview
      schedule modified. Recruitment for interviews ceased when category saturation was
      achieved. CONCLUSION: PNs and GPs differed widely in their descriptions of how
      they prepare a women for a smear. PNs reported following routines which they felt
      incorporated women's questions and anxieties; GPs reported that the discussion
      with the woman depended on the reason for doing the smear but also the amount of
      time available within the consultation. Few respondents reported raising issues
      of reliability or sensitivity of the test with women, neither did they report
      discussing with women the possibility of an abnormal smear result or what further
      investigation and treatment may be required. The degree of persuasion reported by
      practitioners used to encourage women to attend for smears varied and was related
      to their attitudes to the national cervical screening programme. PRACTICE
      IMPLICATIONS: The current system for recall being separate from practice
      activity, whilst ensuring accuracy of the data-base, may limit the opportunity
      for information-giving which is sensitive to the needs to the local population.
      There is a need to include consent issues in the training of PNs, rather than
      just practical aspects of smear-taking, and to formalise training updates for
      GPs. In addition, the taking of opportunistic smears and the constraints placed
      upon time and information-giving need addressing. The role of other primary care
      staff in encouraging women to attend for smears raises training needs for these
      staff which practices or primary care trusts must address.

PMID- 15964736
TI  - The Four Habits Coding Scheme: validation of an instrument to assess clinicians'
      communication behavior.
AB  - OBJECTIVE: To present preliminary evidence for the reliability and validity of
      the Four Habits Coding Scheme (4HCS), an instrument based on a teaching model
      used widely throughout Kaiser Permanente to improve clinicians' communication
      skills. METHODS: One hundred videotaped primary care visits were coded using the
      4HCS, and the data were assessed against a previously available data set for
      these visits, including the Roter Interaction Analysis System (RIAS), back
      channel responses, measures of nonverbal behavior, length of visit, and patients'
      post-visit assessments. RESULTS: Levels of inter-rater reliability were
      acceptable, and the distribution of ratings across items indicated that
      physicians' modal responses varied widely. Correlations between 4HCS ratings,
      RIAS, back channel responses, and non-verbal measures provided evidence of the
      instrument's construct validity. CONCLUSIONS: The Four Habits Coding Scheme, an
      instrument that combines both evaluative and descriptive elements of physician
      communication behavior and is derived from a conceptually based teaching model,
      has the potential to be of utility to researchers and evaluators as well as
      educators and clinicians. PRACTICE IMPLICATIONS: The Four Habits Coding Scheme
      provides a template for both guiding and measuring physician communication
      behaviors.

PMID- 15964737
TI  - Expression of Borrelia burgdorferi erp genes during infection of non-human
      primates.
AB  - All examined isolates of the Lyme disease spirochete contain multiple operons
      encoding Erp outer membrane lipoproteins. Many Erp proteins have been
      demonstrated to bind the host complement regulator factor H, and may thereby help
      protect the bacteria from complement-mediated killing during mammalian infection.
      Consistent with that hypothesis, all Erp proteins are produced by Borrelia
      burgdorferi during transmission between tick vectors and mammalian hosts. The
      present study examined whether erp genes are also expressed by B. burgdorferi
      following establishment of mammalian infection. To that end, quantitative RT-PCR
      was utilized to assess erp transcription levels within different tissues of
      infected non-human primates, a model that closely mimics human Lyme disease. The
      majority of erp genes were detectably transcribed after more than 3 months of
      mammalian infection. Intriguingly, differences in expression levels were noted
      among the various erp loci. No significant differences in erp expression were
      apparent between examined tissues, which included central and peripheral nervous
      system tissue, skeletal muscle, bladder, skin and heart tissues. These data
      strongly suggest that Erp proteins are expressed by B. burgdorferi throughout
      infection of their vertebrate hosts.

PMID- 15964738
TI  - Mapping molecular responses to xenoestrogens through Gene Ontology and pathway
      analysis of toxicogenomic data.
AB  - The recent sequencing of mammalian genomes has driven the development of genomic
      technologies, including microarray-based gene expression profiling, that allow
      simultaneous measurement of the expression levels of thousands of genes. Gene
      expression profiling applied to toxicology (toxicogenomics) has the potential to
      reveal, holistically, the molecular pathways and cellular processes that mediate
      the adverse responses to a toxicant. However, the initial output of a
      toxicogenomics experiment consists of a list of genes whose expression is altered
      upon toxicant exposure. In order to interpret these data in a biological context,
      new bioinformatic methods must be developed to place gene expression changes in
      the context of the underlying pathways and processes affected. One emerging
      approach is the application of Gene Ontology (GO) mapping and pathway analysis to
      gene expression profiling data. The utility of this in mechanistic toxicology
      will be illustrated using examples in which GO mapping of toxicogenomic data has
      provided novel insights into the molecular mechanisms induced by exposure to
      xenoestrogens.

PMID- 15964739
TI  - 2D and 3D assessment of neuropathology in rat brain after prenatal exposure to
      methylazoxymethanol, a model for developmental neurotoxicty.
AB  - To evaluate the ability of a tiered quantitative morphological approach to reveal
      developmental neurotoxicity, morphometric parameters were measured in the
      offspring of rats treated with methylazoxymethanol (MAM) during days 13-15 of
      pregnancy. Treatment was aimed at inhibiting the proliferation phase of
      hippocampal neurons while leaving cerebellar neurons unaffected. 2D and 3D
      assessment of brain morphology combined with straightforward measurement of brain
      size, weight and volume, and the usefulness of estimation of total neuron numbers
      were studied. Each tier indicated major effects of MAM, from macroscopic effects
      in the cerebrum (first tier) to a considerable loss of neurons in the hippocampal
      CA1 pyramidal layer (third tier). The cerebellum and the number of cerebellar
      granular neurons were not changed. Along with each step of the proposed tiered
      approach (brain size-->linear morphometry-->stereology), the discriminative
      strength of the endpoints, and thus the probability to pinpoint the extent and
      location of developmental brain lesions increased.

PMID- 15964740
TI  - Chaos in voice, from modeling to measurement.
AB  - Chaos has been observed in turbulence, chemical reactions, nonlinear circuits,
      the solar system, biological populations, and seems to be an essential aspect of
      most physical systems. Chaos may also be central to the interpretation of
      irregularity in voice disorders. This presentation will summarize the results
      from a series of our recent studies. These studies have demonstrated the
      prescence of chaos in computer models of vocal folds, experiments with excised
      larynges, and human voices. Methods based on nonlinear dynamics can be used to
      quantify chaos and irregularity in vocal fold vibration. Studies have suggested
      that disordered voices from laryngeal pathologies such as laryngeal paralysis,
      vocal polyps, and vocal nodules might exhibit chaotic behaviors. Conventional
      parameters, such as jitter and shimmer, may be unreliable for analysis of
      periodic and chaotic voice signals. Nonlinear dynamic methods, however, have
      differentiated between normal and pathological phonations and can describe the
      aperiodic or chaotic voice. Chaos theory and nonlinear dynamics can enchance our
      understanding and therefore our assessment of pathological phonation.

PMID- 15964741
TI  - Current understanding and review of the literature: vocal fold scarring.
AB  - Vocal fold scarring is the greatest cause of poor voice after vocal fold injury.
      Scarring causes a disruption of the viscoelastic layered structure of the lamina
      propria, an increase in stiffness of the vibratory structure, and glottic
      incompetence. Current treatments for this complex condition are inconsistent and
      often produce suboptimal results. Research investigating this condition has
      dramatically increased over the last several years. The literature has been
      directed toward understanding vocal fold scarring at the biological level and
      translating this to the clinical forum. We present an up-to-date, thorough, and
      scholarly review of the literature in vocal fold scarring since 1996.

PMID- 15964742
TI  - Increased serum S100B in elderly, chronic schizophrenic patients: negative
      correlation with deficit symptoms.
AB  - In schizophrenia, elevations of serum and CSF S100B levels have been reported and
      related to state of the disease and negative symptoms. In elderly chronic
      schizophrenic inpatients with stable medication, S100B may be increased and
      correlated to psychopathology and neuropsychological deficits. We have measured
      serum levels of S100B in 41 elderly, chronic schizophrenic patients and 23 age-
      and gender-matched controls using an immunoluminometric assay. In patients, we
      assessed detailed psychopathology and neuropsychological performance and
      determined serum levels of haloperidol, clozapine and its two main metabolites
      desmethylclozapine and clozapine metabolite N-oxid by HPLC. S100B levels were
      increased in elderly chronic schizophrenic patients compared to healthy controls.
      In patients, levels were negatively correlated with deficit symptoms and
      positively with age. There were no significant differences of S100B between
      medication groups and no correlation with serum levels of antipsychotics or
      neuropsychological scores. Elevations of S100B in elderly chronic schizophrenic
      patients may be related to an active disease process lasting until old-age.
      Correlations point to the impact of S100B in neuroplasticity and ageing. Post
      mortem studies should clarify the presence of altered S100B function in the brain
      and its relationship to neuroplastic or neurodegenerative processes.

PMID- 15964743
TI  - Clinicians' recognition of the metabolic adverse effects of antipsychotic
      medications.
AB  - There is a growing concern regarding the propensity of second generation
      antipsychotics (SGAs) to induce weight gain and metabolic adverse effects. Recent
      consensus guidelines have recommended assessment and monitoring procedures to
      appropriately detect and manage these adverse effects. This study addresses the
      appreciation and readiness of clinicians to implement management guidelines for
      these adverse effects. Respondents indicated awareness of the risks of treatment
      with SGAs. The extent of monitoring for metabolic adverse effects was low and
      inconsistent across measures and in frequency of evaluation. Ongoing efforts are
      needed to support and encourage change in clinician practice.

PMID- 15964744
TI  - Zinc eluted from siliconized latex urinary catheters does not affect the in vitro
      activity of antifungal agents against Candida spp.

PMID- 15964745
TI  - Efficacy of a short-term psychoeducational intervention for persistent non
      organic insomnia in severely mentally ill patients. A pilot study.
AB  - Insomnia in psychiatric patients is frequently underestimated in clinical
      practice. Usually drugs are prescribed for the treatment of this disorder but non
      pharmacological intervention can be successfully used. The present study aimed at
      evaluating the efficacy of a two-session psychoeducational intervention in
      improving persistent non-organic insomnia and reducing the administration of PRN
      therapy in severely mentally ill patients. A pre-post study was performed on 36
      psychiatric patients admitted to a residential psychiatric unit. The Nocturnal
      Sleep Onset Scale (NSOS) and Daytime Sleepiness Scale (DSS), the sleep onset
      latency, the time awake after sleep onset and the numbers of awakenings were
      gathered 2 weeks before the intervention (T0), immediately prior the intervention
      (T1), 2 weeks after the last session of the intervention (T2) and a 3-month
      follow-up (T3). The total number of administrations of PRN therapy from T0 to T1
      and from T1 to T2 were also examined. A significant reduction was shown on the
      NSOS, the sleep onset latency and in the time awake after sleep onset from T1 to
      T2 and from T1 to T3, while no significant difference was found between T0 and
      T1. A significant decrease on the mean number of administrations of PRN therapy
      was also found between 15 days before the intervention (T0-T1) and 15 days after
      intervention (T1-T2). The initial results of this study seems to suggest the
      possible efficacy of a short-term psychoeducational intervention on improving
      persistent non-organic insomnia in severely mentally ill patients. Further
      control studies are necessary to confirm these findings.

PMID- 15964746
TI  - The use of atypical antipsychotics in the treatment of catatonia.
AB  - PURPOSE: Evidence indicates that classical antipsychotics may aggravate non
      malignant and malignant catatonia (MC). Atypical antipsychotics are less likely
      to cause movement disorders than classical antipsychotics and they are being
      frequently prescribed in disorders that can be associated with catatonia.
      Therefore, the important question that arises is whether atypical antipsychotics
      have a role to play in the treatment of catatonia. MATERIALS AND METHODS: A
      Medline search was performed to locate papers on the use of atypical
      antipsychotics in catatonia published between 1970 and 31st December 2004.
      RESULTS: The literature on the use of atypical antipsychotics in catatonia
      consists of case reports and retrospective studies. In most cases of non-MC a
      reduction of the catatonic symptoms is reported upon treatment with atypical
      antipsychotics. Cases of MC relate mainly to the neuroleptic malignant syndrome
      (NMS), which is considered as an iatrogenic stuporous variant of MC caused by
      antipsychotics. CONCLUSION: There are indications that atypical antipsychotics
      may be useful in non-MC. As a consequence, one should not only focus on the
      possible extrapyramidal and autonomic side effects of these drugs, but also on
      the possible beneficial effects on certain brain functions and on the catatonic
      symptomatology. However, randomized controlled trials are needed to evaluate the
      effect of these drugs, and caution is advisable, since cases of NMS have been
      linked to treatment with atypical antipsychotics. There is no evidence to
      prescribe atypical antipsychotics in MC.

PMID- 15964747
TI  - A comparative study of fluoxetine, moclobemide, and tianeptine in the treatment
      of posttraumatic stress disorder following an earthquake.
AB  - PURPOSE: Although antidepressant drugs have been proven as an effective treatment
      for posttraumatic stress disorder (PTSD), there are few comparative studies of
      antidepressants that are acting on different neurotransmitters. The main aim of
      this study is to compare the efficacy of different class of antidepressant drugs
      on the PTSD. SUBJECTS/MATERIALS AND METHODS: In this open label study, the
      patients who met DSM-IV criteria for PTSD were randomly assigned to flexible
      doses of fluoxetine, moclobemide, or tianeptine. After the first assessment,
      consecutive assessments were performed at the end of weeks 2, 4, 8, and 12 using
      clinician administered PTSD scale (CAPS) and Clinical Global Impression of
      Severity (CGI-S). Changes in the total score of CAPS and sub-scale scores of
      symptom clusters (re-experience, avoidance, and hyperarousal) were the main
      output of efficacy. All statistics were based on intention-to-treat and last
      observation-carried-forward (LOCF) principles. RESULTS: Thirty-eight patients
      were assigned to fluoxetine, 35 patients were assigned to moclobemide, and 30
      patients were assigned to tianeptine group. Gender distributions and mean ages of
      the treatment groups were not significantly different. Drop-out rates due to an
      adverse events or unknown reasons were not significantly different among
      fluoxetine (18.4%), moclobemide (14.3%), and tianeptine (20.0%) groups. All three
      treatments has led to a significant improvement in PTSD severity assessed with
      CAPS total score (ANOVA P < 0.001). Similarly, total scores of re-experiencing,
      avoidance, and hyperarousal clusters that are subscales of CAPS were
      significantly reduced by all three treatments (with ANOVA all P values < 0.001).
      There was not significant difference in terms of treatment effect between three
      groups. DISCUSSION: Treatment groups showed very similar improvement on all
      ratings scales. The findings support that fluoxetine, moclobemide, and tianeptine
      are all effective in the treatment of PTSD. Different mechanisms of action for
      these antidepressant drugs might result in the same common neurochemical end
      point. However, further studies using different classes of antidepressant drugs
      are needed.

PMID- 15964748
TI  - Change in perfusion, hallucinations and fluctuations in consciousness in dementia
      with Lewy bodies.
AB  - Fluctuations in consciousness and visual hallucinations are common
      neuropsychiatric features of dementia with Lewy bodies and Parkinson's disease
      dementia. To investigate potential neural correlates, we compared how changes in
      brain perfusion over a 1-year period were related to changes in the severity of
      these key clinical features. We recruited 29 subjects with either Parkinson's
      disease with dementia (15 subjects) or dementia with Lewy bodies (14 subjects).
      Cerebral perfusion was measured using HMPAO SPECT at baseline, and repeated 1
      year later. The presence of hallucinations (Neuropsychiatric Inventory), severity
      of fluctuations in consciousness (fluctuation assessment scale) and cognitive
      ability (CAMCOG) were assessed at both time points. After controlling for changes
      in cognitive ability and effect of cholinesterase medication, we found a
      significant correlation between an increase in perfusion in midline posterior
      cingulate and decrease in hallucination severity. There was also a significant
      correlation between increased fluctuations of consciousness and increased
      thalamic and decreased inferior occipital perfusion. We have identified important
      neural correlates of key clinical features in Lewy body dementia and postulate
      that the associations can be understood through the influence of the cholinergic
      system on attention.

PMID- 15964749
TI  - Primary study on the application of Serum Pharmacology in Chinese traditional
      medicine.
AB  - In the paper, two main methods, which are Serum Pharmacology and Traditional
      Pharmacology, were adopted to study Chinese traditional medicine, such as Ginkgo
      biloba extract (GBE), ginsenosides (GS) and compound GG (GBE+GS), pharmacology in
      vitro. The results showed that there were evident difference between the results
      of Serum Pharmacology and that of Traditional Pharmacology. There was no
      significant difference between the drug effect of crude GS on nitric oxide (NO)
      production in ECV304 and that of crude GBE, and the drug effect of GG was
      superior to that of GS and GBE, respectively. But, compared with GBE serum, the
      GS serum up-regulation of NO production in ECV304 increased significantly, and
      the GG serum up-regulation of the NO production in ECV304 was inferior to that of
      GS serum and GBE serum significantly. The results suggested that Serum
      Pharmacological study should be adopted in the pharmacological investigation on
      the Chinese traditional medicine and the drug screening of the Chinese
      traditional medicine.

PMID- 15964750
TI  - Effects of selective COX-2 and 5-LOX inhibition on prostaglandin and leukotriene
      synthesis in ductal pancreatic cancer in Syrian hamster.
AB  - Selective inhibition of eicosanoid synthesis seems to decrease carcinogenesis,
      however, the effect on liver metastasis in pancreatic cancer is still unknown.
      Ductal pancreatic adenocarcinoma was chemically induced by weekly injection of N
      nitrosobis-2-oxopropylamine (BOP) in Syrian hamster. Animals received selective
      inhibition of cyclooxygenase-2 (Celebrex) and 5-lipoxygenase (Zyflo). In week 33,
      hamsters were sacrificed and incidence of pancreatic carcinomas as well as liver
      metastases were examined. Furthermore, size and number of liver metastases per
      animal were determined and concentration of PGF1alpha, PGE2 and leukotrienes was
      measured in hepatic and pancreatic tissue. Combined therapy (Celebrex+Zyflo)
      significantly decreased incidence, number and size of liver metastases.
      Furthermore extra- and intrametastatic concentration of PGE2 was reduced by this
      treatment in hepatic tissue. Single Cox-2-inhibition (Celebrex) decreased
      intrametastatic hepatic PGF1alpha and PGE2 concentration while PGF1alpha
      concentration was reduced in non-metastatic liver (nml). Moreover 5-LOX
      inhibition (Zyflo) decreased intrametastatic PGE2 concentration as well as
      PGF1alpha and PGE2 in nml. In pancreatic carcinomas highest LT-concentration was
      found after combined treatment and this therapy group was the only one revealing
      a significantly higher amount of LTs in carcinomas compared to tumour-free
      tissue. Hepatic LT-concentration was significantly lower in the control groups
      than in nml of the tumour groups. Combination of Cox-2-inhibition and 5-Lox
      inhibition might be a suitable adjuvant therapy to prevent liver metastasis in
      human ductal pancreatic adenocarcinoma.

PMID- 15964751
TI  - Can airway obstruction be estimated by lung auscultation in an emergency room
      setting?
AB  - OBJECTIVE: Lung auscultation is a central part of the physical examination at
      hospital admission. In this study, the physicians' estimation of airway
      obstruction by auscultation was determined and compared with the degree of airway
      obstruction as measured by FEV(1)/FVC values. METHODS: Two hundred and thirty
      three patients consecutively admitted to the medical emergency room with chest
      problems were included. After taking their history, patients were auscultated by
      an Internal Medicine registrar. The degree of airway obstruction had to be
      estimated (0=no, 1=mild, 2=moderate and 3=severe obstructed) and then spirometry
      was performed. Airway obstruction was defined as a ratio of FEV(1)/FVC <70%. The
      degree of airway obstruction was defined on FEV(1)/FVC as mild (FEV(1)/FVC <70%
      and >50%), moderate (FEV(1)/FVC <50% >30%) and severe (FEV(1)/FVC <30%). RESULTS:
      One hundred and thirty-five patients (57.9%) had no sign of airway obstruction
      (FEV(1)/FVC >70%). Spirometry showed a mild obstruction in 51 patients (21.9%), a
      moderate obstruction in 27 patients (11.6%) and a severe obstruction in 20
      patients (8.6%). There was a weak but significant correlation between FEV(1)/FVC
      and the auscultation-based estimation of airway obstruction in Internal Medicine
      Registrars (Spearman's rho=0.328; P<0.001). The sensitivity to detect airway
      obstruction by lung auscultation was 72.6% and the specificity only 46.3%. Thus,
      the negative predictive value was 68% and the positive predictive value 51%. In
      27 patients (9.7%), airway obstruction was missed by lung auscultation. In these
      27 cases, the severity of airway obstruction was mild in 20 patients, moderate in
      5 patients and severe in 2 patients. In 82 patients (29.4%) with no sign of
      airway obstruction (FEV(1)/FVC >70%), airway obstruction was wrongly estimated as
      mild in 42 patients, as moderate in 34 patients and as severe in 6 patients,
      respectively. By performing multiple logistic regression, normal lung
      auscultation was a significant and independent predictor for not having an airway
      obstruction (OR 2.48 (1.43-4.28); P=0.001). CONCLUSION: Under emergency room
      conditions, physicians can quite accurately exclude airway obstruction by
      auscultation. Normal lung auscultation is an independent predictor for not having
      an airway obstruction. However, airway obstruction is often overestimated by
      auscultation; thus, spirometry should be performed.

PMID- 15964752
TI  - Production of biodiesel from waste frying oils.
AB  - Waste frying oils transesterification was studied with the purpose of achieving
      the best conditions for biodiesel production. Transesterification reactions were
      carried out for 1 h using waste frying oils (WFOs), methanol, and sodium
      hydroxide as catalyst. In order to determine the best conditions for biodiesel
      production, a series of experiments were carried out, using methanol/WFO molar
      ratios between 3.6 and 5.4 and catalyst/WFO weight ratios between 0.2% and 1.0%.
      For oils with an acid value of 0.42 mg KOH/g, results show that a methanol/WFO
      ratio of 4.8 and a catalyst/WFO ratio of 0.6% gives the highest yield of methyl
      esters. Furthermore, an increase in the amount of methanol or catalyst quantity
      seems to simplify the separation/purification of the methyl esters phase, as
      showed by a viscosity reduction and an increasing purity to values higher than
      98% for methyl esters phase.

PMID- 15964753
TI  - Displacement imprinted polymer receptor analysis (DIPRA) for chlorophenolic
      contaminants in drinking water and packaging materials.
AB  - The preparation of a molecularly imprinted polymer (MIP) for pentachlorophenol is
      described together with two alternative reporter derivatives for use in a
      displacement imprinted polymer receptor analysis (DIPRA) format procedure. In
      this procedure, alternative reporter molecules were rebound to the synthetic
      receptor sites and their displacement by the target analyte was employed as the
      basis of a simple procedure for the measurement of chlorophenols in water and
      packaging material samples. Water samples were extracted using the standard
      procedure (EPA 528) and a detection limit of 0.5 microg l(-1) was achieved using
      the DIPRA detection method, with good agreement between the displacement
      technique and GC-ECD analysis. A variety of packaging materials, extracted using
      a buffered detergent solution were also analysed using the DIPRA procedure and
      showed good agreement with GC results. In addition, investigation of the cross
      reactivity of a range of pesticides and materials commonly encountered in
      environmental analysis indicated the procedure gave good discrimination between
      pesticides bearing a chlorophenolic moiety and other materials. The procedure is
      considered highly suitable for use as a rapid field-test method or for
      incorporation into a test kit device.

PMID- 15964754
TI  - Hemichordates and the origin of chordates.
AB  - Hemichordates, the phylum of bilateral animals most closely related to chordates,
      could reveal the evolutionary origins of chordate traits such as the nerve cord,
      notochord, gill slits and tail. The anteroposterior maps of gene expression
      domains for 38 genes of chordate neural patterning are highly similar for
      hemichordates and chordates, even though hemichordates have a diffuse nerve-net.
      About 40% of the domains are not present in protostome maps. We propose that this
      map, the gill slits and the tail date to the deuterostome ancestor. The map of
      dorsoventral expression domains, centered on a Bmp-Chordin axis, differs between
      the two groups; hemichordates resemble protostomes more than they do chordates.
      The dorsoventral axis might have undergone extensive modification in the chordate
      line, including centralization of the nervous system, segregation of epidermis,
      derivation of the notochord, and an inversion of organization.

PMID- 15964755
TI  - Flower development and evolution: gene duplication, diversification and
      redeployment.
AB  - Gene duplication and diversification can provide the raw material for the
      evolution of new morphologies. In plants, the numbers of MADS-box genes have
      multiplied considerably, resulting in a plethora of these transcriptional
      regulators in the angiosperms (flowering plants). MADS-box genes have been
      implicated in the regulation of a variety of flower developmental processes;
      therefore, understanding the functional consequences of duplication and
      diversification in this gene family can shed light on the evolution of different
      floral forms. Recent functional analyses of MADS-box gene lineages have
      demonstrated that in various instances these genes have swapped roles, acquired
      novel roles, or retained ancestral roles. These studies underscore the idea that
      gene function cannot be extrapolated from structural orthology.

PMID- 15964756
TI  - The fall and rise of apical dominance.
AB  - The plant hormone auxin, synthesised in the shoot apex, moves down the stem and
      inhibits lateral branching. Auxin does not travel upward into the branches, so it
      must act indirectly; for example, through a second messenger. However, recent
      work on auxin transport suggests a possible additional mechanism whereby auxin
      transport in the stem prevents the establishment of auxin transport out of the
      branches, inhibiting their growth.

PMID- 15964757
TI  - Watching tubules glow and branch.
AB  - Branching morphogenesis is an important mechanism of animal development yet,
      until recently, most details about this highly dynamic process have had to be
      inferred from fixed tissues. Several groups have now developed transgenic animals
      in which branching tubules express fluorescent proteins, enabling their
      morphogenesis to be studied dynamically using time-lapse microscopy. The results
      have shown that branch emergence is highly variable, that sprouting tracheae and
      blood vessels guide themselves by filopodial projections, that branching
      morphogenesis can involve highly ordered cell rearrangements, and that branches
      are subject to intense remodelling. Though they are very new, these fluorescent
      systems have already expanded our knowledge of branching morphogenesis; future
      work, in which fluorescence might be used to report processes in addition to
      anatomy, promises an even greater advance.

PMID- 15964758
TI  - Structure-activity relationships within a series of caspase inhibitors. Part 2:
      Heterocyclic warheads.
AB  - Various heterocyclic hetero-methyl ketones of the 1-naphthyloxyacetyl-Val-Asp
      backbone have been prepared. A study of their structure-activity relationship
      (SAR) related to caspase-1, -3, -6, and -8 is reported. Their efficacy in a
      cellular model of cell death is also discussed. Potent broad-spectrum caspase
      inhibitors have been identified.

PMID- 15964759
TI  - The role of estimating muscle-tendon lengths and velocities of the hamstrings in
      the evaluation and treatment of crouch gait.
AB  - Persons with cerebral palsy frequently walk with excessive knee flexion during
      terminal swing and stance. This gait abnormality is often attributed to "short"
      or "spastic" hamstrings that restrict knee extension, and is often treated by
      hamstrings lengthening surgery. At present, the outcomes of these procedures are
      inconsistent. This study examined whether analyses of the muscle-tendon lengths
      and lengthening velocities of patients' hamstrings during walking may be helpful
      when deciding whether a candidate is likely to benefit from hamstrings surgery.
      One hundred and fifty-two subjects were cross-classified in a series of multi-way
      contingency tables based on their pre- and postoperative gait kinematics, muscle
      tendon lengths, muscle-tendon velocities, and hamstrings surgeries. The lengths
      and velocities of the subjects' semimembranosus muscles were estimated by
      combining kinematic data from gait analysis with a three-dimensional computer
      model of the lower extremity. Log-linear analysis revealed that the subjects who
      walked with abnormally "short" or "slow" hamstrings preoperatively, and whose
      hamstrings did not operate at longer lengths or faster velocities
      postoperatively, were unlikely to walk with improved knee extension after
      treatment (p < 0.05). Subjects who did not walk with abnormally short or slow
      hamstrings preoperatively, and whose hamstrings did operate at longer lengths or
      faster velocities postoperatively, tended to exhibit unimproved or worsened
      anterior pelvic tilt after treatment (p < 0.05). Examination of the muscle-tendon
      lengths and velocities allows individuals who walk with abnormally short or slow
      hamstrings to be distinguished from those who do not, and thus may help to
      identify patients who are at risk for unsatisfactory postsurgical changes in knee
      extension or anterior pelvic tilt.

PMID- 15964760
TI  - A new structural alternative in benzo[b]furans for antimicrobial activity.
AB  - Two series of 2-substituted and three new diacetyl benzofurans were synthesized
      through palladium-catalyzed reactions and their in vitro antimicrobial spectra
      were assessed. The compounds demonstrated mild to significant growth inhibition
      against antibiotic-susceptible standard and clinically isolated strains of Gram
      positive and Gram-negative bacteria as well as human fungal pathogens. Ampicillin
      and kanamycin were used as references for antibacterial screening; nystatin and
      amphotericin B were used for antifungal screening. Varying substitution at the
      benzofuran moiety and subsequent antimicrobial screening identified the C-3
      acetyl functionality as a new structural alternative for optimal antimicrobial
      property in the benzofuran class of compounds.

PMID- 15964762
TI  - Giant aneurysms of the sinuses of Valsalva and aortic regurgitation in a patient
      with Noonan's syndrome.
AB  - Noonan's syndrome is one of the commonest hereditary syndromes with cardiac
      involvement. We report a rare presentation of this syndrome, associated with
      giant aneurysms of the left and non-coronary sinuses of Valsalva, resulting in
      symptomatic aortic valve regurgitation. The patient's clinical investigations and
      operative management are presented. Histological examination of aortic tissues
      offers insight into the pathogenesis of these complications.

PMID- 15964763
TI  - Transdiaphragmatic migration of forgotten gauze sponge: an unreported entity of
      lung abscess.
AB  - Migration of left in foreign bodies like gauze sponge into intestine, stomach,
      urinary bladder and their extrusion through umbilicus or rectum is well known. We
      report a unique case wherein a gauze sponge was left in abdominal cavity 25 years
      back at the time of initial surgery. This patient who had not undergone any
      thoracic surgery in the past was recently subjected to posterolateral thoracotomy
      for a right sided lung abscess and a large sponge gauze was unbelievably
      recovered from the area of lung abscess.

PMID- 15964764
TI  - Thimerosal-induced cytosolic Ca2+ elevation and subsequent cell death in human
      osteosarcoma cells.
AB  - The effect of the oxidizing agent thimerosal on cytosolic free Ca(2+)
      concentration ([Ca(2+)]i) and proliferation has not been explored in human
      osteoblast-like cells. This study examined whether thimerosal alters Ca(2+)
      levels and causes cell death in MG63 human osteosarcoma cells. [Ca(2+)]i and cell
      death were measured using the fluorescent dyes fura-2 and WST-1, respectively.
      Thimerosal at concentrations above 5 microM increased [Ca(2+)]i in a
      concentration-dependent manner. The Ca(2+) signal was reduced by 80% by removing
      extracellular Ca(2+). The thimerosal-induced Ca(2+) influx was sensitive to
      blockade of La(3+), and dithiothreitol (50 microM) but was insensitive to nickel
      and several L-type Ca(2+) channel blockers. After pretreatment with 1 microM
      thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor), thimerosal failed
      to induce [Ca(2+)]i rises. Inhibition of phospholipase C with 2 microM U73122 did
      not change thimerosal-induced [Ca(2+)]i rises. At concentrations of 5, 10 and 20
      microM thimerosal killed 33, 55 and 100% cells, respectively. The cytotoxic
      effect of 5 microM thimerosal was reversed by 54% by prechelating cytosolic
      Ca(2+) with BAPTA. Collectively, in MG63 cells, thimerosal induced a [Ca(2+)]i
      rise by causing Ca(2+) release from endoplasmic reticulum stores and Ca(2+)
      influx from extracellular space. Furthermore, thimerosal can cause Ca(2+)-related
      cytotoxicity in a concentration-dependent manner.

PMID- 15964765
TI  - Differential expression of individual gamma-protocadherins during mouse brain
      development.
AB  - Three tandemly arrayed protocadherin gene clusters (Pcdh-alpha, -beta, -gamma)
      comprising more than 50 genes are found in human and mouse. Here, we have
      investigated the expression and distribution of individual gamma-protocadherins
      (Pcdhs-gamma) in the developing mouse brain. We find that transfection of Pcdh
      gamma genes promotes calcium-dependent cell adhesion in HEK 293 cells.
      Furthermore, Pcdh-gamma can be recruited to synapses of transfected primary
      hippocampal neurons. Several individual members of the in total 22 Pcdhs-gamma
      were chosen to examine the expression of the three subfamilies, Pcdh-gammaA, 
      gammaB, and -gammaC. These Pcdh-gamma transcripts are expressed all over the
      brain, with minor regional and cell-type specific differences. Interestingly, a
      distinct, later onset of expression is observed for Pcdh-gammaC5, a gene located
      at the end of the Pcdh-gamma cluster. Largely overlapping expression patterns of
      individual Pcdh-gamma proteins are detected with anti-peptide antibodies. Small
      differences are observed in the staining of dendritic processes and synapse-rich
      layers. Our results support the idea that Pcdhs-gamma participate in neuronal
      differentiation and may be implicated in the fine-tuning of neuronal morphology
      and synaptogenesis. Cell autonomous regulation of transcription might generate
      the widespread distribution of individual Pcdhs-gamma in the brain, which is
      strikingly different from the restricted expression patterns observed for
      classical cadherins. Thus, a defined set of Pcdhs-gamma may engage in neuronal
      adhesion and signaling on the cellular level.

PMID- 15964766
TI  - A resolution criterion for electron tomography based on cross-validation.
AB  - Despite much progress in electron tomography, quantitative assessment of
      resolution has remained a problematic issue. The criteria that are used in single
      particle analysis, based on gauging the consistency between density maps
      calculated from half data sets, are not directly applicable because of the
      uniqueness of a tomographic volume. Here, we propose two criteria based on a
      cross-validation approach. One, called FSC(e/o), is based on a Fourier shell
      correlation comparison between tomograms calculated from the even and odd members
      of a tilt series. The other, called noise-compensated leave-one-out (NLOO), is
      based on Fourier ring correlation comparisons between an original projection and
      the corresponding reprojection of the tomogram calculated from all the other
      projections, taking into account the differing noise statistics. Plotted as a
      function of tilt angle, they allow assessment of the angular dependence of
      resolution and quality control over the series of projections. Integrated over
      all projections, the results give a global figure for resolution. Tests on
      simulated tomograms established consistency between these criteria and the
      FSC(ref), a correlation coefficient calculated between a known reference
      structure and the corresponding portion of a tomogram containing that structure.
      The two criteria-FSC(e/o) and NLOO-are mutually consistent when residual noise is
      the major resolution-limiting factor. When the size of the tilt increment becomes
      a significant factor, NLOO provides a more reliable criterion, as expected,
      although it is computationally intensive. Applicable to entire tomograms or
      selected structures, NLOO has also been tested on experimental tomographic data.

PMID- 15964767
TI  - Preliminary analysis of two and three dimensional crystals of vault
      ribonucleoprotein particles.
AB  - Vaults are large ribonucleoprotein particles found in a wide variety of
      eukaryotes. When imaged by electron-microscopy vaults present a strikingly
      conserved barrel-shaped structure with an invaginated waist and two protruding
      caps. In this work, we present two dimensional (2D) and three dimensional (3D)
      crystals of naturally produced vaults in murine and monkey cells, respectively.
      The 2D-crystals presented a hexagonal packing with the lattice parameter defined
      by the diameter of the vault barrel. Fourier transforms from images of the
      negatively stained 2D-crystals showed spots till about 45 A resolution. The 3D
      crystals reached about 0.15 x 0.15 x 0.02 mm3 in size and presented a flat
      triangular morphology with well-developed faces. The preliminary characterization
      of these 3D-crystals, which diffract very weakly to approximately 10 A
      resolution, suggests a trigonal packing with the R32 space group symmetry. The 3D
      crystals appear to be formed by adding layers of vaults, which retain the
      hexagonal organization seen in the 2D-crystals, with relative shifts that
      maximize the interdigitation of particles in adjacent layers. Accurate crystal
      symmetry in the 2D- and 3D-crystals requires neighbor particles interacting
      according to a 6-fold and a 3-fold dihedral symmetry, respectively. Compatibility
      with the reported 8-fold symmetry would imply multiples of 24-fold rotational
      symmetry, in agreement with the recently proposed 48-fold dihedral symmetry for
      reconstituted recombinant vaults.

PMID- 15964768
TI  - Rapid radiation and cryptic speciation in mediterranean triplefin blennies
      (Pisces: Tripterygiidae) combining multiple genes.
AB  - The genus Tripterygion is the unique genus of the family Tripterygiidae in the
      Mediterranean Sea and in the northeastern Atlantic coast. Three species and four
      subspecies had been described: Tripterygion tripteronotus and Tripterygion
      melanurus (T. m. melanurus and T. m. minor) are endemic of the Mediterranean, and
      T. delaisi (T. d. delaisi and T. d. xanthosoma) is found in both areas. We used
      five different genes (12S, 16S, tRNA-val, COI, and 18S) to elucidate their
      taxonomy status and their phylogenetic relationships. We employed different
      phylogenetic reconstructions that yielded different tree topologies. This
      discrepancy may be caused by the speciation process making difficult the
      reconstruction of a highly supported tree. All pair comparisons between these
      three species showed the same genetic divergence indicating that the speciation
      process could have been resolved by a rapid radiation event after the Messinian
      Salinity Crisis (5.2Mya) leading to a trichotomy. Our molecular data revealed two
      clearly supported clades within T. tripteronotus, whose divergence largely
      exceeded that found between other fish species, consequently these two groups
      should be considered two cryptic species diverging 2.75-3.32Mya along the
      Pliocene glaciations. On the contrary, none of the genes studied supported the
      existence of two subspecies of T. melanurus. Finally, the two subspecies of T.
      delaisi were validated and probably originated during the Quaternary climatic
      fluctuations (1.10-1.23Mya), however their distribution ranges should be
      redefined.

PMID- 15964769
TI  - Mitochondrial diversity of Opsariichthys bidens (Teleostei, Cyprinidae) in three
      Chinese drainages.
AB  - We describe the phylogeographic structure of 28 Chinese populations of the
      cyprinid Opsariichthys bidens across three main Chinese river drainages. Our
      study is based on the phylogenetic analysis of the complete mitochondrial
      cytochrome b gene (1140 bp). We combined this analysis with population processes
      inferred from nested clade analysis (NCA) and mismatch distributions. Both
      analyses showed that Chinese O. bidens consists of five mtDNA lineages
      (Opsariichthys 1-5) with high genetic divergence among them. Molecular
      divergences (TrN+G) higher than 20% among the Opsariichthys 1-5 mtDNA lineages
      suggest a taxonomic underestimation at the species level. About 92% of the
      genetic variance among samples was explained by differences among Opsariichthys
      mtDNA lineages. Drainage-restricted haplotypes with high frequencies and moderate
      nucleotide diversity show that Opsariichthys populations have evolved
      independently. NCA results were congruent with the phylogeny, and unimodal
      mismatch distributions with negative Tajima's D values suggest population
      expansions in some Opsariichthys lineages. The phylogeographic structure of the
      Opsariichthys 1-5 mtDNA lineages appears to be related to their long-term
      interruption of gene flow (theta(ST)>0.97). Our results suggested that
      fragmentation of ancestral ranges might have caused Opsariichthys diversification
      in Chinese waters. However, current distribution of common haplotypes across the
      Yangtze and Pearl drainages suggests a recent river connection that could have
      favoured gene flow across drainages. Overall, the results indicated that the
      richness of current Asian widespread species might have been underestimated, and
      that the cyprinid populations of O. bidens in the Yangtze, Pearl and Hai He
      drainages may correspond to five species.

PMID- 15964770
TI  - In vivo serial joint space measurements during dynamic loading in a canine model
      of osteoarthritis.
AB  - OBJECTIVE: To devise a reliable, sensitive method to measure joint space in vivo
      during dynamic loading. Additionally, to determine if dynamic joint space changes
      were related to the severity of long-term cartilage damage. DESIGN: Subjects were
      23 adult foxhounds (18 experimental, 5 control). Experimental subjects had
      surgically transected cranial cruciate ligaments (CCL). Dynamic joint space was
      serially measured in vivo over 2 years using a unique high speed stereo
      radiographic system in combination with subject-specific computed tomography
      reconstructions. RESULTS: Dynamic joint space was measured in vivo with a within
      day precision of 0.09 mm. Half of the experimental subjects developed minor
      articular cartilage damage and the other half developed severe articular
      cartilage damage in the medial knee compartment. Joint space during treadmill
      running increased significantly in the minor damage group in both the medial
      (+0.61 mm, P = 0.036) and lateral (+0.84 mm, P = 0.002) compartments of the knee.
      Dynamic joint space in the severe damage group did not increase significantly on
      either the medial (+0.27 mm, P = 0.408) or lateral (+0.44 mm, P = 0.199) side.
      The majority of the change in joint space occurred the first year after CCL
      transection. Medial meniscus damage was related to severity of medial articular
      cartilage damage (tau = 0.447, P = 0.003). The minor damage group developed 73%
      of all osteophytes noted at dissection. CONCLUSIONS: This technique is a precise
      tool for measuring joint space serially in vivo under dynamic loading conditions.
      The data suggest decreased severity in long-term articular cartilage damage is
      related to: osteophyte formation, less severe medial meniscus damage and
      increased joint space the first 12 months after injury.

PMID- 15964771
TI  - Total laparoscopic aortic surgery: transperitoneal direct approach.
AB  - OBJECTIVE: We describe the laparoscopic transperitoneal direct approach to the
      abdominal aorta. OPERATIVE TECHNIQUE: The patient is placed in the right lateral
      decubitus position, which allows dropping of the small bowel into right side of
      the abdomen. Anatomical exposure of the abdominal aorta follows the same steps as
      in open surgery. DISCUSSION: Laparoscopic transperitoneal direct approach allows
      a reproducible exposure of the abdominal aorta. This technique was useful when
      retrocolic and/or retrorenal approaches were not possible because of previous
      left nephrectomy.

PMID- 15964772
TI  - Automatic ankle pressure measurements using PPG in ankle-brachial pressure index
      determination.
AB  - OBJECTIVE: To evaluate a new technique using a photoplethysmographic (PPG) probe
      for automatic ankle pressure measurements. DESIGN: Comparative study on two
      techniques for ankle pressure measurement. SETTING: University hospital.
      MATERIAL: Thirty-five patients with leg arterial disease and eight healthy
      volunteers. Ankle-brachial indices (ABPI) were measured using conventional CW
      Doppler technique and PPG-based prototype equipment for the ankle pressure
      recordings. CHIEF OUTCOME MEASURES: ABPIs calculated from CW Doppler and PPG
      ankle pressure measurements. The PPG signals were analysed both by visual
      judgement and by a software based, automatic algorithm. MAIN RESULTS: The mean
      difference between ABPIs calculated from CW Doppler recordings and PPG (visual
      analysis) was -0.01 (limits of agreement (+/-two standard deviations) +0.16 to 
      0.19). The correlation coefficient was 0.93. When the algorithm was used, the
      mean difference (CW Doppler-PPG) was 0.05 (limits of agreement 0.28 to -0.18,
      r=0.89). CONCLUSIONS: The PPG method is a promising technique with an inherent
      potential for automatisation of the ankle pressure measurements, thereby reducing
      the observer-dependency in ABPI recordings.

PMID- 15964774
TI  - Dynamics of virus infections involved in the bovine respiratory disease complex
      in Swedish dairy herds.
AB  - The dynamics of bovine respiratory syncytial virus (BRSV), bovine parainfluenza
      virus 3 (PIV-3), bovine corona virus (BCoV) and bovine viral diarrhoea virus
      (BVDV) infections were studied in 118 dairy herds in south western Sweden. By
      using serology on paired samples from three approximately 7 vs. approximately 15
      month-old calves per herd, the propagation of infections was investigated over
      about a 1-year period. The results implied that at least 74% of calves had
      experienced one or more of the monitored infections at the age of approximately 7
      months (Sample 1, Spring); 30%, 48%, 34% and 8% were seropositive to BRSV, PIV-3,
      BCoV and BVDV, respectively. Seroconversions to BRSV, PIV-3, BCoV and BVDV
      occurred in 26%, 38%, 50% and 3% of seronegative animals and 63% had antibodies
      against two or more infections at approximately 15 months (Sample 2). In total,
      90-97% of animals that were seropositive in Sample 1 remained positive in Sample
      2. A significant association was found between BVDV and BCoV (P = 0.01).
      Moreover, a significantly higher proportion of herds in which no calves had a
      recorded history of respiratory disease (n = 15) were classified as negative to
      all four infections monitored when compared to herds in which disease was
      observed (P = 0.0002). This study showed a high infection burden in young animals
      and effective spread of BRSV, PIV-3 and BCoV in one area of Sweden. BVDV
      infections were restricted to a few herds, reflecting the effect of a voluntary
      control program against BVDV in Sweden.

PMID- 15964775
TI  - A review of intrathecal morphine therapy related granulomas.
AB  - The development of catheter associated granulomatous masses in intrathecal
      morphine therapy is an uncommon, but potentially serious problem. While these
      systems have historically been used in patients with short life expectancies,
      more recently patients with pain from a benign source have benefited from this
      therapy, and new complications are being encountered secondary to the patients'
      longer life spans. Morphine is the most commonly used intrathecal opioid and
      evidence exists that the formation of granulomatous masses are related to the use
      of higher doses. When the patients' requirement of morphine increases
      significantly, the physician should be alert for signs of spinal cord
      compression, such as new neurological deficits, myelopathy, or radiculopathy.
      Patients that require these higher doses should be properly informed of the
      association with granulomas and their associated risks. Indolent infection may
      also be the etiology of granulomatous masses, and the presence of organisms, both
      aerobic and anaerobic, should be routinely investigated. Patients with catheter
      associated granulomas appear to share several features. They exhibit the onset of
      symptoms several months following the initiation of intraspinal opioids and
      commonly present with an increase in pain that precedes signs and symptoms of
      neurological deterioration. While MRI might be the preferred method of detection
      of intrathecal granulomas, its cost and availability are prohibitive for routine
      screening. CT myelogram via pump side port injection of contrast can also be
      performed to detect catheter tip related granulomas/obstructions. Serial
      neurological examinations for new deficits may be performed and recorded during
      pump refill visits to recognize a granulomatous mass in its early stages. If an
      abnormality is identified, imaging studies are appropriate. Awareness of the
      condition and vigilance are the keys to successful management of this
      complication.

PMID- 15964776
TI  - Survival pathways triggered by peroxynitrite in cells belonging to the
      monocyte/macrophage lineage.
AB  - Peroxynitrite, a highly reactive nitrogen species, promotes in U937 cells (a
      promonocytic cell line) a mitochondrial permeability transition (MPT)-dependent
      necrosis. An initial event triggered by peroxynitrite (i.e., inhibition of
      complex III of the mitochondrial respiratory chain) is responsible for the time
      dependent formation of H(2)O(2), essential for the occurrence of cell death.
      Otherwise non-toxic concentrations of peroxynitrite nevertheless commit cells to
      MPT-dependent necrosis, which is however prevented by a cytoprotective signaling
      driven by arachidonic acid (AA) released by the cytosolic PLA(2) isoform.
      Interestingly, the mechanism whereby delayed formation of H(2)O(2) promotes
      toxicity in cells exposed to intrinsically toxic concentrations of peroxynitrite
      is independent of the accumulation of additional damage. Cell death is in fact
      mediated by inhibition of the AA-dependent cytoprotective signaling. Exogenous
      AA, however, prevented toxicity also under these conditions. An additional point
      to be made is that the major findings obtained using U937 cells were reproduced
      in different cell types belonging to the monocyte/macrophage lineage. Hence,
      within the context of the inflammatory response, monocytes and macrophages may
      cope with peroxynitrite by using AA, a signaling molecule largely available at
      the inflammatory sites.

PMID- 15964777
TI  - Molecular characterization of a bifunctional glyoxylate cycle enzyme, malate
      synthase/isocitrate lyase, in Euglena gracilis.
AB  - Euglena gracilis induced glyoxylate cycle enzymes when ethanol was fed as a sole
      carbon source. We purified, cloned and characterized a bifunctional glyoxylate
      cycle enzyme from E. gracilis (EgGCE). This enzyme consists of an N-terminal
      malate synthase (MS) domain fused to a C-terminal isocitrate lyase (ICL) domain
      in a single polypeptide chain. This domain order is inverted compared to the
      bifunctional glyoxylate cycle enzyme in Caenorhabditis elegans, an N-terminal ICL
      domain fused to a C-terminal MS domain. Purified EgGCE catalyzed the sequential
      ICL and MS reactions. ICL activity of purified EgGCE increased in the existence
      of acetyl-CoA at a concentration of micro-molar order. We discussed the
      physiological roles of the bifunctional glyoxylate cycle enzyme in these
      organisms as well as its molecular evolution.

PMID- 15964778
TI  - Acid- and pressure-induced (un)folding of yeast glutathione reductase:
      competition between protein oligomerization and aggregation.
AB  - Glutathione reductase (GR) is a homodimeric flavoenzyme involved in cellular
      defense against oxidative stress. In the present study, we have used a
      combination of acidic pH and hydrostatic pressure to investigate the (un)folding
      transition of yeast GR. Our results indicate that at pH 2 a distinct partially
      folded state is stabilized, as judged by intrinsic fluorescence, bis ANS binding
      and circular dichroism (CD) analysis. Further characterization of this partially
      folded state by size exclusion chromatography revealed that it corresponds to
      expanded GR monomers. CD analysis at pH 2 showed a significant loss of secondary
      structure. The partially folded GR monomers stabilized at pH 2 were fully and
      reversibly unfolded using hydrostatic pressure (up to 3.5kbar) as a thermodynamic
      perturbant. By contrast, return to physiological pH after exposure to acidic pH
      led to a competing reaction between refolding dimerization and aggregation of GR.
      These results support the notion that a partially folded intermediate state is
      not only critical for folding of GR but also appears to be a seed for protein
      aggregation.

PMID- 15964779
TI  - The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine
      kinases.
AB  - Axl belongs to a particular subfamily of transmembrane receptor tyrosine kinases,
      the biological ligand for which is the growth/survival factor Gas6. However,
      little is known about the molecular mechanisms for Axl activation and signal
      transduction. We have previously identified a novel interaction between the
      intracellular domain of Axl and Ran binding protein in microtubule organising
      centre (RanBPM). In the present study, we investigated further the nature of the
      RanBPM interaction with Axl. A wide distribution of RanBPM mRNA expression in
      human tissues and various human cancer cell lines was detected. The strength of
      interaction of both proteins in yeast was comparable to that with the other Axl
      binding proteins phosphatidylinositol 3-kinase and Grb2. A truncated version of
      RanBPM with the SPRY-LisH domain region omitted failed to interact with Axl in
      yeast. RanBPM was also found to interact in yeast with the Axl homologue,
      Sky/Tyro3. The interaction between Axl intracellular domain and RanBPM was
      reproduced in coimmunoprecipitation experiments in both cell-free and mammalian
      cell systems. Furthermore, coimmunoprecipitation revealed endogenous Axl and
      RanBPM to interact in several mammalian cell lines in a constitutive manner.
      Stimulation of COS cells with Gas6 caused increased Axl tyrosine phosphorylation
      although appeared not to influence the RanBPM-Axl association. In conclusion, we
      have identified and characterised a novel interaction between RanBPM and the
      related receptor tyrosine kinases, Axl and Sky. This novel insight into the
      signalling interactions of Axl and Sky may shed further light on their suspected
      roles in tumourigenesis, inflammation as well as other cell proliferative
      diseases.

PMID- 15964781
TI  - The role of the spleen and immunization against malaria.

PMID- 15964780
TI  - Adding insight: a qualitative cross-site study of physician order entry.
AB  - The research questions, strategies, and results of a 7-year qualitative study of
      computerized physician order entry implementation (CPOE) at successful sites are
      reviewed over time. The iterative nature of qualitative inquiry stimulates a
      consecutive stream of research foci, which, with each iteration, add further
      insight into the overarching research question. A multidisciplinary team of
      researchers studied CPOE implementation in four organizations using a multi
      method approach to address the question "what are the success factors for
      implementing CPOE?" Four major themes emerged after studying three sites; ten
      themes resulted from blending the first results with those from a fourth site;
      and twelve principles were generated when results of a qualitative analysis of
      consensus conference transcripts were combined with the field data. The study has
      produced detailed descriptions of factors related to CPOE success and insight
      into the implementation process.

PMID- 15964782
TI  - Omenn's syndrome occurring in patients without mutations in recombination
      activating genes.
AB  - Omenn syndrome (OS) is characterised by hepatosplenomegaly, lymphadenopathy,
      erythema, eosinophilia, elevated IgE, oligoclonal T cell expansions and
      recombinase activating gene (RAG) mutations. We investigated 9 cases of OS to
      correlate genotype with immunophenotype using a two-color flow cytometry with
      monoclonal antibodies against CD3 and TCRVB families to map TCRVB usage. T and B
      clonal cell populations were examined in peripheral blood lymphocytes by PCR and
      sequencing of TCRB/TCRG T cell and IGH FR2/FR3 B cell products. RAG and Artemis
      genes were sequenced from genomic DNA. All patients demonstrated absent TCRVB
      families; six had predominant TCRVB families, six oligoclonal TCR gene
      rearrangements including TCRGD rearrangements. One demonstrated functional IGH
      rearrangement, an observation not previously reported. In this clinically
      homogeneous population, with similar immunological phenotype, RAG mutations were
      identified in only 2/9 patients. OS is a genetically heterogeneous condition, and
      patients with similar immunophenotypes may have as yet unidentified gene defects.

PMID- 15964783
TI  - Development of the baroreflex in the young rat.
AB  - The baroreceptor-heart period reflex was assessed in conscious, freely behaving
      rat pups on postnatal days 6 and 14. The baroreceptor-heart period reflex was
      elicited using the alpha1-adrenergic agonist phenylephrine to increase blood
      pressure and the vasodilator, sodium nitroprusside, to decrease blood pressure.
      The autonomic effects of the baroreceptor manipulations were determined using
      pharmacological autonomic blockade. The data demonstrate that vasoconstriction
      produces a potent baroreflex-mediated bradycardia as early as postnatal day 6,
      which had previously been demonstrated only in anesthetized pups. In the
      anesthetized pup, the bradycardia is mediated by vagal activation, while we
      demonstrate that both vagal activation and sympathetic withdrawal occur in
      unanesthetized animals. In addition, the results replicate previous findings in
      rats demonstrating minimal cardiac sympathetic activation or vagal withdrawal
      following vasodilation during the first week of life, but substantial baroreflex
      mediated tachycardia by the second week.

PMID- 15964784
TI  - Depressor responses to L-proline microinjected into the rat ventrolateral medulla
      are mediated by ionotropic excitatory amino acid receptors.
AB  - The essential amino acid L-proline produces a depressor response when
      microinjected into the caudal ventrolateral medulla (CVLM) of anesthetized rats.
      L-proline may activate some excitatory amino acid (EAA) receptors. The present
      study tested this hypothesis by investigating the effects of two ionotropic
      excitatory amino acid receptor antagonists on the depressor response to L-proline
      in the CVLM: the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      (AMPA)/kainate receptor-selective antagonist 6-cyano-7-nitroquinoxaline-2,3-dione
      (CNQX) and the N-methyl-D-aspartate (NMDA) receptor-selective antagonist MK801.
      Urethane-anesthetized rats received arterial catheters and their ventrolateral
      medulla surface was exposed. Injections of the antagonists CNQX and MK801 (2 mM,
      68 nl in each case) into the CVLM completely blocked depressor responses to
      subsequent administration of AMPA (2 pmol/34 nl) and NMDA (2 pmol/34 nl),
      respectively. The depressor response to L-proline (3.4 nmol/34 nl) was strongly
      inhibited by prior injection of CNQX (2 mM, 68 nl) and significantly attenuated
      by prior injection of a high dose (20 mM, 68 nl), but not a low dose (2 mM, 68
      nl), of MK801. The results indicate that the depressor response to L-proline in
      the CVLM includes mechanisms of ionotropic excitatory amino acid receptors.

PMID- 15964785
TI  - Viral respiratory infections in cystic fibrosis.
AB  - Viral respiratory infections in CF patients are associated with an increase in
      morbidity at short and long term. Viral infections have a greater impact on CF
      patients compared to non-CF controls. They result in increased respiratory
      symptoms, deterioration of Shwachman and radiological scores, prolonged
      hospitalizations, a persistent decrease of pulmonary function, increased use of
      antibiotics and a higher frequency of exacerbations at follow-up. In addition,
      interaction between viruses and bacteria in CF is suggested. Some studies observe
      increased new bacterial colonization and raised antipseudomonal antibodies in
      episodes of viral respiratory infections. Experimental data suggest that
      increased virus replication, impaired specific anti-bacterial defense and
      increased adherence of bacteria play a role in the pathogenesis of viral
      respiratory infections in CF. Further knowledge about the role of viruses and
      interaction with bacteria in CF lung disease might result in new therapeutic
      strategies to improve prognosis of CF patients.

PMID- 15964786
TI  - Determinants of inspiratory activity.
AB  - In vitro and in vivo studies have identified the pre-Botzinger complex as an
      important kernel for the generation of inspiratory activity. The mechanisms
      underlying inspiratory rhythm generation involve pacemaker as well as synaptic
      mechanisms. In slice preparations, blockade of pacemaker properties with blockers
      for the persistent Na+ current, and the Ca2+-activated inward cationic current,
      abolishes respiratory activity. Here we show that blockade of the persistent Na+
      current alone is sufficient to abolish respiratory activity in the in situ
      preparation. Although pacemaker neurons may be critical for establishing the
      basic respiratory rhythm, their rhythmic output is modulated by many elements of
      the respiratory network. For example, levels of synaptic inhibition control
      whether they burst or not, and endogenously released neuromodulators, such as
      serotonin and substance P modulate their intrinsic membrane currents. We
      hypothesize that the balance between synaptic and intrinsic pacemaker properties
      in the respiratory network is plastic, and that alterations of this balance may
      lead to dynamic reconfigurations of the respiratory network, which ultimately
      give rise to different activity patterns.

PMID- 15964787
TI  - Are time preference and body mass index associated? Evidence from the National
      Longitudinal Survey of Youth.
AB  - The prevalence of obesity among both adults and children in the U.S. has risen to
      all time highs in the past two decades. We propose that an increase in the
      marginal rate of time preference has contributed to increasing obesity. More
      people are consuming more calories than they expend because they have become less
      willing to trade current pleasure for potential future health benefits.
      Accordingly, this paper explores the association between body mass index (BMI)
      and time preference. We use the National Longitudinal Survey of Youth (NLSY79) to
      test our hypothesis that time preference and BMI are positively related. We find
      some evidence that there is such a positive association among black and Hispanic
      men and black women.

PMID- 15964788
TI  - Early stages of salmon calcitonin aggregation: effect induced by ageing and
      oxidation processes in water and in the presence of model membranes.
AB  - The natural ageing- and hydrogen peroxide-induced aggregation of salmon
      calcitonin were studied in water and in the presence of
      dipalmitoylphosphatidylcholine (DPPC) liposomes. The early stages of the
      aggregation process at low protein concentration were investigated by means of
      Circular Dichroism spectroscopy (CD) and conventional and immunogold labelling
      Transmission Electron Microscopy (TEM). In buffered water solution, salmon
      calcitonin showed a two-stage conformational variation related to fibril
      formation and phase-separation of larger aggregates. A first stage, characterised
      by small conformational changes but a decrease in dichroic band intensity, was
      followed by a second stage, 6 days after, leading to higher conformational
      variations and aggregations. Salmon calcitonin showed a distinct modification in
      the secondary structure and aggregate morphology in the presence of hydrogen
      peroxide with respect to natural ageing, indicating that the two aggregation
      processes (natural and chemical-induced) followed a distinct mechanism. The
      oxidised forms of the peptide were separated by liquid chromatography. The same
      study was performed in the presence of DPPC liposomes. The results obtained by
      conventional and immunogold labelling TEM evidenced that salmon calcitonin in
      buffered water solution essentially does not enter the liposomes but forms around
      them a fibril network characterised by the same conformational changes after 6
      days. The oxidised sample in the presence of liposomes showed a "fibrils hank",
      separated from liposomes. The presence of liposomes did not affect either the
      aggregation or the conformational modifications yet observed by TEM and CD in
      water solution.

PMID- 15964789
TI  - A subset of nuclear receptor coregulators act as coupling proteins during
      synthesis and maturation of RNA transcripts.

PMID- 15964790
TI  - Aryl hydrocarbon receptor-mediated transcription: ligand-dependent recruitment of
      estrogen receptor alpha to 2,3,7,8-tetrachlorodibenzo-p-dioxin-responsive
      promoters.
AB  - Using chromatin immunoprecipitation assays, we studied the 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD)-mediated recruitment of the aryl hydrocarbon
      receptor (AhR) and several co-regulators to the CYP1A1 promoter. AhR displayed a
      time-dependent recruitment, reaching a peak at 75 min and maintaining promoter
      occupancy for the remainder of the time course. Recruitment of AhR was followed
      by TIF2/SRC2, which preceded CBP, histone H3 acetylation, and RNA polymerase II
      (RNAPII). Simultaneous recruitment to the enhancer and the TATA box region
      suggests the formation of a large multiprotein complex bridging the two promoter
      regions. Interestingly, estrogen receptor alpha (ERalpha) displayed a TCDD- and
      time-dependent recruitment to the CYP1A1 promoter, which was increased by co
      treatment with estradiol. Transfection in HuH7 human liver cells confirmed
      previously reported ERalpha enhancement of AhR activity. In contrast, TCDD did
      not induce the recruitment of ERalpha to the estrogen-responsive pS2 promoter,
      and after 120 min of co-treatment with estradiol, ERalpha is still present on the
      CYP1A1 promoter but no longer at pS2. RNA interference studies with T47D cells
      support a role for ERalpha in TCDD-dependent CYP1A1 expression. Our data suggest
      that ERalpha acts as a coregulator of AhR-mediated transcriptional activation and
      that the recruitment of ERalpha by AhR represents a novel mechanism AhR-ERalpha
      cross talk.

PMID- 15964791
TI  - Inhibition of MuSK expression by CREB interacting with a CRE-like element and
      MyoD.
AB  - The type I receptor-like protein tyrosine kinase MuSK is essential for the
      neuromuscular junction formation. MuSK expression is tightly regulated during
      development, but the underlying mechanisms were unclear. Here we identified a
      novel mechanism by which MuSK expression may be regulated. A cyclic AMP response
      element (CRE)-like element in the 5'-flanking region of the MuSK gene binds to
      CREB1 (CRE-binding protein 1). Mutation of this element increases the MuSK
      promoter activity, suggesting a role for CREB1 in attenuation of MuSK expression.
      Interestingly, CREB mutants unable to bind to DNA also inhibit MuSK promoter
      activity, suggesting a CRE-independent inhibitory mechanism. In agreement, CREB1
      could inhibit a mutant MuSK transgene reporter whose CRE site was mutated. We
      provide evidence that CREB interacts directly with MyoD, a myogenic factor
      essential for MuSK expression in muscle cells. Suppression of CREB expression by
      small interfering RNA increases MuSK promoter activity. These results demonstrate
      an important role for CREB1 in the regulation of MuSK expression.

PMID- 15964792
TI  - Subunits of the heterotrimeric transcription factor NF-Y are imported into the
      nucleus by distinct pathways involving importin beta and importin 13.
AB  - The transcriptional activator NF-Y is a heterotrimeric complex composed of NF-YA,
      NF-YB, and NF-YC, which specifically binds the CCAAT consensus present in about
      30% of eukaryotic promoters. All three subunits contain evolutionarily conserved
      core regions, which comprise a histone fold motif (HFM) in the case of NF-YB and
      NF-YC. Our results of in vitro binding studies and nuclear import assays reveal
      two different transport mechanisms for NF-Y subunits. While NF-YA is imported by
      an importin beta-mediated pathway, the NF-YB/NF-YC heterodimer is translocated
      into the nucleus in an importin 13-dependent manner. We define a nonclassical
      nuclear localization signal (ncNLS) in NF-YA, and mutational analysis indicates
      that positively charged amino acid residues in the ncNLS are required for nuclear
      targeting of NF-YA. Importin beta binding is restricted to the monomeric,
      uncomplexed NF-YA subunit. In contrast, the nuclear import of NF-YB and NF-YC
      requires dimer formation. Only the NF-YB/NF-YC dimer, but not the monomeric
      components, are recognized by importin 13 and are imported into the nucleus.
      Importin 13 competes with NF-YA for binding to the NF-YB/NF-YC dimer. Our data
      suggest that a distinct binding platform derived from the HFM of both subunits,
      NF-YB/NF-YC, mediates those interactions.

PMID- 15964793
TI  - The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated
      degradation of Ho endonuclease.
AB  - Ho endonuclease initiates a mating type switch by making a double-strand break at
      the mating type locus, MAT. Ho is marked by phosphorylation for rapid destruction
      by functions of the DNA damage response, MEC1, RAD9, and CHK1. Phosphorylated Ho
      is recruited for ubiquitylation via the SCF ubiquitin ligase complex by the F-box
      protein, Ufo1. Here we identify a further DNA damage-inducible protein, the UbL
      UbA protein Ddi1, specifically required for Ho degradation. Ho interacts only
      with Ddi1; it does not interact with the other UbL-UbA proteins, Rad23 or Dsk2.
      Ho must be ubiquitylated to interact with Ddi1, and there is no interaction when
      Ho is produced in mec1 or Deltaufo1 mutants that do not support its degradation.
      Ddi1 binds the proteasome via its N-terminal ubiquitin-like domain (UbL) and
      interacts with ubiquitylated Ho via its ubiquitin-associated domain (UbA); both
      domains of Ddi1 are required for association of ubiquitylated Ho with the
      proteasome. Despite being a nuclear protein, Ho is exported to the cytoplasm for
      degradation. In the absence of Ddi1, ubiquitylated Ho is stabilized and
      accumulates in the cytoplasm. These results establish a role for Ddi1 in the
      degradation of a natural ubiquitylated substrate. The specific interaction
      between Ho and Ddi1 identifies an additional function associated with DNA damage
      involved in its degradation.

PMID- 15964794
TI  - ATM activation and its recruitment to damaged DNA require binding to the C
      terminus of Nbs1.
AB  - ATM has a central role in controlling the cellular responses to DNA damage. It
      and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical
      HEAT repeat domains in their amino-terminal regions. The functions of these
      domains in PIKKs are not well understood. ATM activation in response to DNA
      damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although
      the exact functional relationship between the MRN complex and ATM is uncertain.
      Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact
      with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles
      nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast
      Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In
      Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where
      it is subsequently autophosphorylated. This interaction is essential for ATM
      activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and
      ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We
      conclude that an interaction between specific HEAT repeats in ATM and the C
      terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that
      conformational changes in the MRN complex that occur upon binding to damaged DNA
      are transmitted through the FXF/Y-HEAT interface to activate ATM. This
      interaction also retains active ATM at sites of DNA damage.

PMID- 15964795
TI  - Mutations in proline 82 of p53 impair its activation by Pin1 and Chk2 in response
      to DNA damage.
AB  - Tumor suppression by the p53 protein largely depends on the elimination of
      damaged cells by apoptosis. Mutations in the polyproline region (PPR) of p53
      impair its apoptotic function. Deletion of the PPR renders p53 more sensitive to
      inhibition by Mdm2 via an unknown mechanism. We have explored the mechanism by
      which the PPR modulates the p53/Mdm2 loop. Proline 82 of p53 was identified to be
      essential for its interaction with the checkpoint kinase 2 (Chk2) and consequent
      phosphorylation of p53 on serine 20, following DNA damage. These physical and
      functional interactions are regulated by Pin1 through cis-trans isomerization of
      proline 82. Our study unravels the pathway by which Pin1 activates p53 in
      response to DNA damage and explains how Pin1 protects p53 from Mdm2. Further, we
      propose a role for Pin1-dependent induction of p53 conformational change as a
      mechanism responsible for the enhanced interaction between p53 and Chk2 following
      DNA damage. Importantly, our findings elucidate the selection for mutations in
      the Pin1 target Thr81/Pro82 motif within the PPR of p53 in human cancer.

PMID- 15964796
TI  - Functional analysis of the roles of posttranslational modifications at the p53 C
      terminus in regulating p53 stability and activity.
AB  - Posttranslational modification of the tumor suppressor p53 plays important roles
      in regulating its stability and activity. Six lysine residues at the p53 C
      terminus can be posttranslationally modified by various mechanisms, including
      acetylation, ubiquitination, neddylation, methylation, and sumoylation. Previous
      cell line transfection studies show that ubiquitination of these lysine residues
      is required for ubiquitin-dependent degradation of p53. In addition, biochemical
      and cell line studies suggested that p53 acetylation at the C terminus might
      stabilize p53 and activate its transcriptional activities. To investigate the
      physiological functional outcome of these C-terminal modifications in regulating
      p53 stability and activity, we introduced missense mutations (lysine to arginine)
      at the six lysine residues (K6R) into the endogenous p53 gene in mouse embryonic
      stem (ES) cells. The K6R mutation prevents all posttranslational modifications at
      these sites but conserves the structure of p53. In contrast to conclusions of
      previous studies, analysis of p53 stability in K6R ES cells, mouse embryonic
      fibroblasts, and thymocytes showed normal p53 stabilization in K6R cells both
      before and after DNA damage, indicating that ubiquitination of these lysine
      residues is not required for efficient p53 degradation. However, p53-dependent
      gene expression was impaired in K6R ES cells and thymocytes in a promoter
      specific manner after DNA damage, indicating that the net outcome of the
      posttranslational modifications at the C terminus is to activate p53
      transcriptional activities after DNA damage.

PMID- 15964797
TI  - The cotranscriptional assembly of snoRNPs controls the biosynthesis of H/ACA
      snoRNAs in Saccharomyces cerevisiae.
AB  - The carboxy-terminal domain (CTD) of RNA polymerase II large subunit acts as a
      platform to assemble the RNA processing machinery in a controlled way throughout
      the transcription cycle. In yeast, recent findings revealed a physical connection
      between phospho-CTD, generated by the Ctk1p kinase, and protein factors having a
      function in small nucleolar RNA (snoRNA) biogenesis. The snoRNAs represent a
      large family of polymerase II noncoding transcripts that are associated with
      highly conserved polypeptides to form stable ribonucleoprotein particles
      (snoRNPs). In this work, we have studied the biogenesis of the snoRNPs belonging
      to the box H/ACA class. We report that the assembly factor Naf1p and the core
      components Cbf5p and Nhp2p are recruited on H/ACA snoRNA genes very early during
      transcription. We also show that the cotranscriptional recruitment of Naf1p and
      Cbf5p is Ctk1p dependent and that Ctk1p and Cbf5p are required for preventing the
      readthrough into the snoRNA downstream genes. All these data suggest that proper
      cotranscriptional snoRNP assembly controls 3'-end formation of snoRNAs and,
      consequently, the release of a functional particle.

PMID- 15964798
TI  - Transcription factor NF-kappaB differentially regulates death receptor 5
      expression involving histone deacetylase 1.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) regulates the
      expression of both anti-apoptotic and proapoptotic genes. Death receptor 5 (DR5,
      TRAIL-R2) is a proapoptotic protein considered to be a potential target for
      cancer therapy, and its expression is mediated by NF-kappaB. The mechanism of NF
      kappaB-induced DR5 expression is, however, unknown. Herein, we determined that
      etoposide-induced DR5 expression requires the first intronic region of the DR5
      gene. Mutation of a putative NF-kappaB binding site in this intron eliminates DR5
      promoter activity, as do mutations in the p53 binding site in this region.
      Reduction in p53 expression also blocks p65 binding to the intronic region of the
      DR5 gene, indicating cooperation between p53 and p65 in DR5 expression. In
      contrast, the anti-apoptotic stimulus, epidermal growth factor (EGF), fails to
      increase DR5 expression but effectively activates NF-kappaB and induces p65
      binding to the DR5 gene. EGF, however, induces the association of histone
      deacetylase 1 (HDAC1) with the DR5 gene, whereas etoposide treatment fails to
      induce this association. Indeed, HDAC inhibitors activate NF-kappaB and p53 and
      upregulate DR5 expression. Blockage of DR5 activation decreased HDAC inhibitor
      induced apoptosis, and a combination of HDAC inhibitors and TRAIL increased
      apoptosis. This provides a mechanism for regulating NF-kappaB-mediated DR5
      expression and could explain the differential roles NF-kappaB plays in regulating
      apoptosis.

PMID- 15964799
TI  - Differential regulation of estrogen-inducible proteolysis and transcription by
      the estrogen receptor alpha N terminus.
AB  - The ubiquitin-proteasome pathway has emerged as an important regulatory mechanism
      governing the activity of several transcription factors. While estrogen receptor
      alpha (ERalpha) is also subjected to rapid ubiquitin-proteasome degradation, the
      relationship between proteolysis and transcriptional regulation is incompletely
      understood. Based on studies primarily focusing on the C-terminal ligand-binding
      and AF-2 transactivation domains, an assembly of an active transcriptional
      complex has been proposed to signal ERalpha proteolysis that is in turn necessary
      for its transcriptional activity. Here, we investigated the role of other regions
      of ERalpha and identified S118 within the N-terminal AF-1 transactivation domain
      as an additional element for regulating estrogen-induced ubiquitination and
      degradation of ERalpha. Significantly, different S118 mutants revealed that
      degradation and transcriptional activity of ERalpha are mechanistically separable
      functions of ERalpha. We find that proteolysis of ERalpha correlates with the
      ability of ERalpha mutants to recruit specific ubiquitin ligases regardless of
      the recruitment of other transcription-related factors to endogenous model target
      genes. Thus, our findings indicate that the AF-1 domain performs a previously
      unrecognized and important role in controlling ligand-induced receptor
      degradation which permits the uncoupling of estrogen-regulated ERalpha
      proteolysis and transcription.

PMID- 15964800
TI  - Blockade of histone deacetylase inhibitor-induced RelA/p65 acetylation and NF
      kappaB activation potentiates apoptosis in leukemia cells through a process
      mediated by oxidative damage, XIAP downregulation, and c-Jun N-terminal kinase 1
      activation.
AB  - NF-kappaB activation is reciprocally regulated by RelA/p65 acetylation and
      deacetylation, which are mediated by histone acetyltransferases (HATs) and
      deacetylases (HDACs). Here we demonstrate that in leukemia cells, NF-kappaB
      activation by the HDAC inhibitors (HDACIs) MS-275 and suberoylanilide hydroxamic
      acid was associated with hyperacetylation and nuclear translocation of RelA/p65.
      The latter events, as well as the association of RelA/p65 with IkappaBalpha, were
      strikingly diminished by either coadministration of the IkappaBalpha
      phosphorylation inhibitor Bay 11-7082 (Bay) or transfection with an IkappaBalpha
      superrepressor. Inhibition of NF-kappaB by pharmacological inhibitors or genetic
      strategies markedly potentiated apoptosis induced by HDACIs, and this was
      accompanied by enhanced reactive oxygen species (ROS) generation, downregulation
      of Mn-superoxide dismutase and XIAP, and c-Jun N-terminal kinase 1 (JNK1)
      activation. Conversely, N-acetyl L-cysteine blocked apoptosis induced by
      Bay/HDACIs by abrogating ROS generation. Inhibition of JNK1 activation attenuated
      Bay/HDACI lethality without affecting NF-kappaB inactivation and ROS generation.
      Finally, XIAP overexpression dramatically protected cells against the Bay/HDACI
      regimen but failed to prevent ROS production and JNK1 activation. Together, these
      data suggest that HDACIs promote the accumulation of acetylated RelA/p65 in the
      nucleus, leading to NF-kappaB activation. Moreover, interference with these
      events by either pharmacological or genetic means leads to a dramatic increase in
      HDACI-mediated lethality through enhanced oxidative damage, downregulation of NF
      kappaB-dependent antiapoptotic proteins, and stress-related JNK1 activation.

PMID- 15964801
TI  - Replication protein A-directed unloading of PCNA by the Ctf18 cohesion
      establishment complex.
AB  - The replication clamp PCNA is loaded around DNA by replication factor C (RFC) and
      functions in DNA replication and repair. Regulated unloading of PCNA during the
      progression and termination of DNA replication may require additional factors.
      Here we show that a Saccharomyces cerevisiae complex required for the
      establishment of sister chromatid cohesion functions as an efficient unloader of
      PCNA. Unloading requires ATP hydrolysis. This seven-subunit Ctf18-RFC complex
      consists of the four small subunits of RFC, together with Ctf18, Dcc1, and Ctf8.
      Ctf18-RFC was also a weak loader of PCNA onto naked template-primer DNA. However,
      when the single-stranded DNA template was coated by the yeast single-stranded DNA
      binding protein replication protein A (RPA) but not by a mutant form of RPA or a
      heterologous single-stranded DNA binding protein, both binding of Ctf18-RFC to
      substrate DNA and loading of PCNA were strongly inhibited, and unloading
      predominated. Neither yeast RFC itself nor two other related clamp loaders,
      containing either Rad24 or Elg1, catalyzed significant unloading of PCNA. The
      Dcc1 and Ctf8 subunits of Ctf18-RFC, while required for establishing sister
      chromatid cohesion in vivo, did not function specifically in PCNA unloading in
      vitro, thereby separating the functionality of the Ctf18-RFC complex into two
      distinct paths.

PMID- 15964802
TI  - Stat1 and Stat2 but not Stat3 arbitrate contradictory growth signals elicited by
      alpha/beta interferon in T lymphocytes.
AB  - Alpha/beta interferon (IFN-alpha/beta) triggers antiviral and antiproliferative
      responses in target cells through modulation of gene expression. The JAK-STAT
      pathway is the major mediator of these biological effects through the activation
      of the transcription factors STAT1 and STAT2, and gene ablation studies have
      demonstrated that both STAT1 and STAT2 are required for most antiviral responses
      induced by IFN-alpha/beta. However, additional signaling pathways are also
      activated by IFN. Here, we show that these additional pathways provoke a
      proliferative response in activated T lymphocytes. While activation of IFN
      stimulated gene factor 3 produces a dominant inhibitory signal capable of
      overriding the mitogenic response, absence of either STAT1 or STAT2 leads to a
      proliferative response to IFN. Growth stimulation by IFN-alpha/beta is
      independent of other STAT proteins, particularly of STAT3, since T lymphocytes
      from STAT1-STAT3 double-knockout mice are growth stimulated by IFN-alpha/beta
      treatment. IFN-alpha/beta can cooperate with numerous T-cell mitogens, including
      interleukin-2 (IL-2), IL-4, IL-7, and IL-12, and can contribute to the rapid
      restoration of the thymus following glucocorticoid-mediated ablation. These
      results underscore the complexity of the cellular response to IFN and suggest
      that the ultimate outcome of IFN action results from a balance between growth
      inhibitory and -stimulatory effects.

PMID- 15964804
TI  - Eukaryotic translation initiation factor 5 is critical for integrity of the
      scanning preinitiation complex and accurate control of GCN4 translation.
AB  - The integrity of eukaryotic translation initiation factor (eIF) interactions in
      ribosomal pre-initiation complexes is critical for the proper regulation of GCN4
      mRNA translation in response to amino acid availability. Increased
      phosphorylation of eIF2 under amino acid starvation conditions leads to a
      corresponding increase in GCN4 mRNA translation. The carboxyl-terminal domain
      (CTD) of eIF5 (eIF5-CTD) has been identified as a potential nucleation site for
      pre-initiation complex assembly. To further characterize eIF5 and delineate its
      role in GCN4 translational control, we isolated mutations leading to temperature
      sensitivity (Ts- phenotype) targeted at TIF5, the structural gene encoding eIF5
      in yeast (Saccharomyces cerevisiae). Nine single point mutations were isolated,
      in addition to an allele in which the last 15 amino acids were deleted. The nine
      point mutations clustered in the eIF5-CTD, which contains two conserved
      aromatic/acidic boxes. Six of the point mutations derepressed GCN4 translation
      independent of eIF2 phosphorylation (Gcd- phenotype) at a permissive temperature,
      directly implicating eIF5-CTD in the eIF2/GTP/Met-tRNA(i)Met ternary complex
      binding process required for GCN4 translational control. In addition, stronger
      restriction of eIF5-CTD function at an elevated temperature led to failure to
      derepress GCN4 translation (Gcn- phenotype) in all of the mutants, most likely
      due to leaky scanning of the first upstream open reading frame of GCN4 mRNA. This
      latter result directly implicates eIF5-CTD in the process of accurate scanning
      for, or recognition of, AUG codons. Taken together, our results indicate that
      eIF5-CTD plays a critical role in both the assembly of the 43S complex and the
      post-assembly process in the 48S complex, likely during the scanning process.

PMID- 15964803
TI  - Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and
      p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in
      adipocytes.
AB  - The sympathetic nervous system regulates the activity and expression of
      uncoupling protein 1 (UCP1) through the three beta-adrenergic receptor subtypes
      and their ability to raise intracellular cyclic AMP (cAMP) levels. Unexpectedly,
      we recently discovered that the cAMP-dependent regulation of multiple genes in
      brown adipocytes, including Ucp1, occurred through the p38 mitogen-activated
      protein kinases (MAPK) (W. Cao, K. W. Daniel, J. Robidoux, P. Puigserver, A. V.
      Medvedev, X. Bai, L. M. Floering, B. M. Spiegelman, and S. Collins, Mol. Cell.
      Biol. 24:3057-3067, 2004). However, no well-defined pathway linking cAMP
      accumulation or cAMP-dependent protein kinase (PKA) to p38 MAPK has been
      described. Therefore, in the present study using both in vivo and in vitro
      models, we have initiated a retrograde approach to define the required
      components, beginning with the p38 MAPK isoforms themselves and the MAP kinase
      kinase(s) that regulates them. Our strategy included ectopic expression of wild
      type and mutant kinases as well as targeted inhibition of gene expression using
      small interfering RNA. The results indicate that the beta-adrenergic receptors
      and PKA lead to a highly selective activation of the p38alpha isoform of MAPK,
      which in turn promotes Ucp1 gene transcription. In addition, this specific
      activation of p38alpha relies solely on the presence of MAP kinase kinase 3,
      despite the expression in brown fat of MKK3, -4, and -6. Finally, of the three
      scaffold proteins of the JIP family expressed in brown adipocytes, only JIP2 co
      immunoprecipitates p38alpha MAPK and MKK3. Therefore, in the brown adipocyte the
      recently described scaffold protein JIP2 assembles the required factors MKK3 and
      p38alpha MAPK linking PKA to the control of thermogenic gene expression.

PMID- 15964805
TI  - Membrane insertion by anthrax protective antigen in cultured cells.
AB  - The enzymatic moieties of anthrax toxin enter the cytosol of mammalian cells via
      a pore in the endosomal membrane formed by the protective antigen (PA) moiety.
      Pore formation involves an acidic pH-induced conformational rearrangement of a
      heptameric precursor (the prepore), in which the seven 2beta2-2beta3 loops
      interact to generate a 14-strand transmembrane beta-barrel. To investigate this
      model in vivo, we labeled PA with the fluorophore 7-nitrobenz-2-oxa-1,3-diazole
      (NBD) at cysteine residues introduced into the 2beta2-2beta3 loop. Each labeled
      PA was bound to CHO cells, and NBD fluorescence was monitored over time in
      stirred cell suspensions or by confocal microscopy. A strong increase was
      observed with NBD at positions 305, 307, 309, and 311, sites where side chains
      are predicted to face the bilayer, and little change was seen at residues 304,
      306, 308, 310, and 312, sites where side chains are predicted to face the pore
      lumen. The increase at position 305 was inhibited by membrane-restricted
      quenchers, low temperature, or various reagents known to affect toxin action. Of
      the 24 NBD attachment sites examined, all but three gave results qualitatively
      consistent with the beta-barrel model. Besides supporting the beta-barrel model
      of membrane insertion, our results describe the time course of insertion and
      identify PA residues where NBD gives a strong signal upon membrane insertion in
      vivo.

PMID- 15964806
TI  - Global analysis of Pub1p targets reveals a coordinate control of gene expression
      through modulation of binding and stability.
AB  - Regulation of mRNA turnover is an important cellular strategy for
      posttranscriptional control of gene expression, mediated by the interplay of cis
      acting sequences and associated trans-acting factors. Pub1p, an ELAV-like yeast
      RNA-binding protein with homology to T-cell internal antigen 1 (TIA-1)/TIA-1
      related protein (TIAR), is an important modulator of the decay of two known
      classes of mRNA. Our goal in this study was to determine the range of mRNAs whose
      stability is dependent on Pub1p, as well as to identify specific transcripts that
      directly bind to this protein. We have examined global mRNA turnover in isogenic
      PUB1 and pub1delta strains through gene expression analysis and demonstrate that
      573 genes exhibit a significant reduction in half-life in a pub1delta strain. We
      also examine the binding specificity of Pub1p using affinity purification
      followed by microarray analysis to comprehensively distinguish between direct and
      indirect targets and find that Pub1p significantly binds to 368 cellular
      transcripts. Among the Pub1p-associated mRNAs, 53 transcripts encoding proteins
      involved in ribosomal biogenesis and cellular metabolism are selectively
      destabilized in the pub1delta strain. In contrast, genes involved in transporter
      activity demonstrate association with Pub1p but display no measurable changes in
      transcript stability. Characterization of two candidate genes, SEC53 and RPS16B,
      demonstrate that both Pub1p-dependent regulation of stability and Pub1p binding
      require 3' untranslated regions, which harbor distinct sequence motifs. These
      results suggest that Pub1p binds to discrete subsets of cellular transcripts and
      posttranscriptionally regulates their expression at multiple levels.

PMID- 15964807
TI  - A novel variant of Inpp5f is imprinted in brain, and its expression is correlated
      with differential methylation of an internal CpG island.
AB  - Using a tissue-specific microarray screen in combination with chromosome
      anomalies in the mouse, we identified a novel imprinted gene, Inpp5f_v2 on mouse
      chromosome 7. Characterization of this gene reveals a 3.2-kb transcript that is
      paternally expressed in the brain. Inpp5f_v2 is a variant of the related 4.7-kb
      transcript, Inpp5f, an inositol phosphatase gene that is biallelically expressed
      in the mouse. Inpp5f_v2 uses an alternative transcriptional start site within an
      intron of Inpp5f and thus has a unique alternative first exon. Whereas other
      imprinted transcripts have a unique first exon located within intron 1 of a
      longer transcript variant (such as at the Gnas and WT1 loci), Inpp5f_v2 is the
      first example of which we are aware in which the alternative first exon of an
      imprinted gene is embedded in a downstream intron (intron 15) of a transcript
      variant. The CpG island associated with the non-imprinted Inpp5f gene is
      hypomethylated on both alleles, a finding consistent with biallelic expression,
      whereas the CpG island present 5' of Inpp5f_v2 is differentially methylated on
      the maternal versus paternal alleles consistent with its imprinting status.

PMID- 15964808
TI  - Esf2p, a U3-associated factor required for small-subunit processome assembly and
      compaction.
AB  - Esf2p is the Saccharomyces cerevisiae homolog of mouse ABT1, a protein previously
      identified as a putative partner of the TATA-element binding protein. However,
      large-scale studies have indicated that Esf2p is primarily localized to the
      nucleolus and that it physically associates with pre-rRNA processing factors.
      Here, we show that Esf2p-depleted cells are defective for pre-rRNA processing at
      the early nucleolar cleavage sites A0 through A2 and consequently are inhibited
      for 18S rRNA synthesis. Esf2p was stably associated with the 5' external
      transcribed spacer (ETS) and the box C+D snoRNA U3, as well as additional box C+D
      snoRNAs and proteins enriched within the small-subunit (SSU) processome/90S
      preribosomes. Esf2p colocalized on glycerol gradients with 90S preribosomes and
      slower migrating particles containing 5' ETS fragments. Strikingly, upon Esf2p
      depletion, chromatin spreads revealed that SSU processome assembly and compaction
      are inhibited and glycerol gradient analysis showed that U3 remains associated
      within 90S preribosomes. This suggests that in the absence of proper SSU
      processome assembly, early pre-rRNA processing is inhibited and U3 is not
      properly released from the 35S pre-rRNAs. The identification of ABT1 in a large
      scale analysis of the human nucleolar proteome indicates that its role may also
      be conserved in mammals.

PMID- 15964809
TI  - The Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex
      requires the Enhancer of Polycomb A domain and chromodomain to acetylate
      nucleosomes.
AB  - Chromatin modification complexes are key gene regulatory factors which
      posttranslationally modify the histone component of chromatin with epigenetic
      marks. To address what features of chromatin modification complexes are
      responsible for the specific recognition of nucleosomes compared to naked
      histones, we have performed a functional dissection of the Esa1-containing
      Saccharomyces cerevisiae Piccolo NuA4 histone acetyltransferase complex. Our
      studies define the Piccolo determinants sufficient to assemble its three subunits
      into a complex as well as Piccolo determinants sufficient to specifically
      acetylate a chromatin template. We find that the conserved Enhancer of Polycomb A
      (EPcA) homology region of the Epl1 component and the N-terminal 165 amino acids
      of the Yng2 component of Piccolo are sufficient with Esa1 to specifically act on
      nucleosomes. We also find that the Esa1 chromodomain plays a critical role in
      Piccolo's ability to distinguish between histones and nucleosomes. In particular,
      specific point mutations in the chromodomain putative hydrophobic cage which
      strongly hinder growth in yeast greatly reduce histone acetyltransferase activity
      on nucleosome substrates, independent of histone methylation or other
      modifications. However, the chromodomain is not required for Piccolo to bind to
      nucleosomes, suggesting a role for the chromodomain in a catalysis step after
      nucleosome binding.

PMID- 15964810
TI  - The survival of motor neurons protein determines the capacity for snRNP assembly:
      biochemical deficiency in spinal muscular atrophy.
AB  - Reduction of the survival of motor neurons (SMN) protein levels causes the motor
      neuron degenerative disease spinal muscular atrophy, the severity of which
      correlates with the extent of reduction in SMN. SMN, together with Gemins 2 to 7,
      forms a complex that functions in the assembly of small nuclear ribonucleoprotein
      particles (snRNPs). Complete depletion of the SMN complex from cell extracts
      abolishes snRNP assembly, the formation of heptameric Sm cores on snRNAs.
      However, what effect, if any, reduction of SMN protein levels, as occurs in
      spinal muscular atrophy patients, has on the capacity of cells to produce snRNPs
      is not known. To address this, we developed a sensitive and quantitative assay
      for snRNP assembly, the formation of high-salt- and heparin-resistant stable Sm
      cores, that is strictly dependent on the SMN complex. We show that the extent of
      Sm core assembly is directly proportional to the amount of SMN protein in cell
      extracts. Consistent with this, pulse-labeling experiments demonstrate a
      significant reduction in the rate of snRNP biogenesis in low-SMN cells.
      Furthermore, extracts of cells from spinal muscular atrophy patients have a lower
      capacity for snRNP assembly that corresponds directly to the reduced amount of
      SMN. Thus, SMN determines the capacity for snRNP biogenesis, and our findings
      provide evidence for a measurable deficiency in a biochemical activity in cells
      from patients with spinal muscular atrophy.

PMID- 15964811
TI  - Histone acetyltransferase activity of p300 is required for transcriptional
      repression by the promyelocytic leukemia zinc finger protein.
AB  - Histone acetyltransferase (HAT) activities of proteins such as p300, CBP, and
      P/CAF play important roles in activation of gene expression. We now show that the
      HAT activity of p300 can also be required for down-regulation of transcription by
      a DNA binding repressor protein. Promyelocytic leukemia zinc finger (PLZF),
      originally identified as a fusion with retinoic acid receptor alpha in rare cases
      of all-trans-retinoic acid-resistant acute promyelocytic leukemia, is a
      transcriptional repressor that recruits histone deacetylase-containing
      corepressor complexes to specific DNA binding sites. PLZF associates with p300 in
      vivo, and its ability to repress transcription is specifically dependent on HAT
      activity of p300 and acetylation of lysines in its C-terminal C2-H2 zinc finger
      motif. An acetylation site mutant of PLZF does not repress transcription and is
      functionally deficient in a colony suppression assay despite retaining its
      abilities to interact with corepressor/histone deacetylase complexes. This is due
      to the fact that acetylation of PLZF activates its ability to bind specific DNA
      sequences both in vitro and in vivo. Taken together, our results indicate that a
      histone deacetylase-dependent transcriptional repressor can be positively
      regulated through acetylation and point to an unexpected role of a coactivator
      protein in transcriptional repression.

PMID- 15964812
TI  - Distinct requirements for Pot1 in limiting telomere length and maintaining
      chromosome stability.
AB  - The fission yeast Pot1 (protection of telomeres) protein binds to the single
      stranded extensions at the ends of telomeres, where its presence is critical for
      the maintenance of linear chromosomes. Homologs of Pot1 have been identified in a
      wide variety of eukaryotes, including plants, animals, and humans. We now show
      that Pot1 plays dual roles in telomere length regulation and chromosome end
      protection. Using a series of Pot1 truncation mutants, we have defined distinct
      areas of the protein required for chromosome stability and for limiting access to
      telomere ends by telomerase. We provide evidence that a large portion of Pot1,
      including the N-terminal DNA binding domain and amino acids close to the C
      terminus, is essential for its protective function. C-terminal Pot1 fragments
      were found to exert a dominant-negative effect by displacing endogenous Pot1 from
      telomeres. Reducing telomere-bound Pot1 in this manner resulted in dramatic
      lengthening of the telomere tract. Upon further reduction of Pot1 at telomeres,
      the opposite phenotype was observed: loss of telomeric DNA and chromosome end
      fusions. Our results demonstrate that cells must carefully regulate the amount of
      telomere-bound Pot1 to differentiate between allowing access to telomerase and
      catastrophic loss of telomeres.

PMID- 15964813
TI  - Dimerization of CUL7 and PARC is not required for all CUL7 functions and mouse
      development.
AB  - CUL7, a recently identified member of the cullin family of E3 ubiquitin ligases,
      forms a unique SCF-like complex and is required for mouse embryonic development.
      To further investigate CUL7 function, we sought to identify CUL7 binding
      proteins. The p53-associated, parkin-like cytoplasmic protein (PARC), a homolog
      of CUL7, was identified as a CUL7-interacting protein by mass spectrometry. The
      heterodimerization of PARC and CUL7, as well as homodimerization of PARC and
      CUL7, was confirmed in vivo. To determine the biological role of PARC by itself
      and in conjunction with CUL7, a targeted deletion of Parc was created in the
      mouse. In contrast to the neonatal lethality of the Cul7 knockout mice, Parc
      knockout mice were born at the expected Mendelian ratios and exhibited no
      apparent phenotype. Additionally, Parc deletion did not appear to affect the
      stability or function of p53. These results suggest that PARC and CUL7 form an
      endogenous complex and that PARC and CUL7 functions are at least partially
      nonoverlapping. In addition, although PARC and p53 form a complex, the absence of
      effect of Parc deletion on p53 stability, localization, and function suggests
      that p53 binding to PARC may serve to control PARC function.

PMID- 15964814
TI  - DREF is required for efficient growth and cell cycle progression in Drosophila
      imaginal discs.
AB  - Based on overexpression studies and target gene analyses, the transcription
      factor DNA replication-related element factor (DREF) has been proposed to
      regulate growth and replication in Drosophila melanogaster. Here we present loss
      of-function experiments to analyze the contribution of DREF to these processes.
      RNA interference-mediated extinction of DREF function in vivo demonstrates a
      requirement for the protein for normal progression through the cell cycle and
      consequently for growth of imaginal discs and the derived adult organs. We show
      that DREF regulates the expression of genes that are required for the transition
      of imaginal disc cells through S phase. In conditions of suppressed apoptosis,
      DREF activation can cause overgrowth of developing organs. These data establish
      DREF as a global regulator of transcriptional programs that mediate cell
      proliferation and organ growth during animal development.

PMID- 15964815
TI  - Mice with a disruption of the thrombospondin 3 gene differ in geometric and
      biomechanical properties of bone and have accelerated development of the femoral
      head.
AB  - Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix
      protein (COMP/TSP5), but its function is unknown. To determine the functional
      significance of TSP3, we generated mice with a targeted disruption of Thbs3. TSP3
      null mice are viable and fertile and show normal prenatal skeletal patterning,
      based on Alcian blue/Alizarin red S staining. However, subtle and transient
      abnormalities were detected in the developing postnatal skeleton. Young adult
      TSP3-null mice are heavier than controls, and analyses of the geometric and
      biomechanical properties of long bones show increases in the moments of inertia,
      endocortical and periostal radii, and failure load. The bones of 9-week-old TSP3
      null male mice also have a significantly greater cortical area. Most of these
      differences were no longer detected in 15-week-old mice. Micro-computed
      tomography scans showed that the trabecular bone proximal to the femoral head
      growth plate developed at an earlier time in TSP3-null mice than in wild-type
      mice. Thus, vascular invasion and ossification start in the femoral heads of TSP3
      null mice at 9 weeks, whereas the wild-type femoral head is still composed of
      hypertrophic chondroctyes in a calcified matrix at 15 weeks. These results
      provide evidence for a role for TSP3 in the regulation of skeletal maturation in
      mice.

PMID- 15964816
TI  - Generation and characterization of mice lacking the zinc uptake transporter ZIP3.
AB  - The mouse ZIP3 (SLC39A3) gene encodes an eight-transmembrane-domain protein that
      has been conserved in mammals and can function to transport zinc. To analyze the
      expression of ZIP3 in the early embryo and neonate and to determine its in vivo
      function, we generated ZIP3 null mice in which the ZIP3 open reading frame was
      replaced with that of the enhanced green fluorescent protein (EGFP) reporter.
      EGFP fluorescence revealed that ZIP3 was expressed in the inner cell mass of the
      blastocyst and later during embryonic development in many tissues. Elevated
      expression was apparent in the embryonic brain and neurotube and neonatal gonads.
      Homozygous knockout mice were viable and fertile and under normal growth
      conditions exhibited no obvious phenotypic abnormalities. Deletion of ZIP3 did
      not alter zinc homeostasis at the molecular level as assessed by essential metal
      levels and the expression of zinc-responsive genes. In knockout mice stressed
      with a zinc-deficient diet during pregnancy or at weaning, a subtle increase in
      the sensitivity to abnormal morphogenesis of the embryo and to depletion of
      thymic pre-T cells, respectively, was noted. These results suggest that this
      protein plays an ancillary role in zinc homeostasis in mice.

PMID- 15964817
TI  - Lack of the central nervous system- and neural crest-expressed forkhead gene
      Foxs1 affects motor function and body weight.
AB  - To gain insight into the expression pattern and functional importance of the
      forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase
      reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type
      (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase
      reporter gene. Staining for beta-galactosidase activity reveals an expression
      pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root
      ganglia as well as several other cell populations in the central nervous system
      (CNS), most prominently the internal granule layer of cerebellum. Other sites of
      expression include the lachrymal gland, outer nuclear layer of retina, enteric
      ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS,
      blood vessel-associated smooth muscle cells and pericytes stain positive for
      Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P < 0.01) on a
      rotating rod than do wt littermates. We have also noted a lower body weight gain
      (P < 0.05) in Foxs1beta-gal/lbeta-gal males on a high-fat diet, and we speculate
      that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in
      regulating body weight via regulation of sympathetic outflow. In support of this,
      we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta
      gal mice. This points toward a role for Foxs1 in the integration and processing
      of neuronal signals of importance for energy turnover and motor function.

PMID- 15964818
TI  - Simultaneous recruitment of coactivators by Gcn4p stimulates multiple steps of
      transcription in vivo.
AB  - Transcriptional activation by Gcn4p is dependent on the coactivators SWI/SNF,
      SAGA, and Srb Mediator, which are recruited by Gcn4p and stimulate assembly of
      the pre-initiation complex (PIC) at the ARG1 promoter in vivo. We show that
      recruitment of all three coactivators is nearly simultaneous with binding of
      Gcn4p at ARG1 and is followed quickly by PIC formation and elongation by RNA
      polymerase II (Pol II) through the open reading frame. Despite the simultaneous
      recruitment of coactivators, rapid recruitment of SWI/SNF depends on the histone
      acetyltransferase (HAT) subunit of SAGA (Gcn5p), a non-HAT function of SAGA, and
      on Mediator. SAGA recruitment in turn is strongly stimulated by Mediator and the
      RSC complex. Recruitment of Mediator, by contrast, occurs independently of the
      other coactivators at ARG1. We confirm the roles of Mediator and SAGA in TATA
      binding protein (TBP) recruitment and demonstrate that all four coactivators
      under study enhance Pol II recruitment or promoter clearance following TBP
      binding. We also present evidence that SWI/SNF and SAGA stimulate transcription
      elongation downstream from the promoter. These functions can be limited to
      discrete time intervals, providing evidence for multiple stages in the induction
      process. Our findings reveal a program of coactivator recruitment and PIC
      assembly that distinguishes Gcn4p from other yeast activators studied thus far.

PMID- 15964819
TI  - Genetic deletion of murine SPRY domain-containing SOCS box protein 2 (SSB-2)
      results in very mild thrombocytopenia.
AB  - The SSB family is comprised of four highly homologous proteins containing a C
      terminal SOCS box motif and a central SPRY domain. No function has yet been
      ascribed to any member of this family in mammalian species despite a clear role
      for other SOCS proteins in negative regulation of cytokine signaling. To
      investigate its physiological role, the murine Ssb-2 gene was deleted by
      homologous recombination. SSB-2-deficient mice were shown to have a reduced rate
      of platelet production, resulting in very mild thrombocytopenia (25% decrease in
      circulating platelets). Tissue histology and other hematological parameters were
      normal, as was the majority of serum biochemistry, with the exception that blood
      urea nitrogen (BUN) levels were decreased in mice lacking SSB-2. Quantitative
      analysis of SSB mRNA levels indicated that SSB-1, -2, and -3 were ubiquitously
      expressed; however, SSB-4 was only expressed at very low levels. SSB-2 expression
      was observed in the kidney and in megakaryocytes, a finding consistent with the
      phenotype of mice lacking this gene. Deletion of SSB-2 thus perturbs the steady
      state level of two tightly controlled homeostatic parameters and identifies a
      critical role for SSB-2 in regulating platelet production and BUN levels.

PMID- 15964820
TI  - Arginine methylation provides epigenetic transcription memory for retinoid
      induced differentiation in myeloid cells.
AB  - Cellular differentiation is governed by changes in gene expression, but at the
      same time, a cell's identity needs to be maintained through multiple cell
      divisions during maturation. In myeloid cell lines, retinoids induce gene
      expression and a well-characterized two-step lineage-specific differentiation. To
      identify mechanisms that contribute to cellular transcriptional memory, we
      analyzed the epigenetic changes taking place on regulatory regions of tissue
      transglutaminase, a gene whose expression is tightly linked to retinoid-induced
      differentiation. Here we report that the induction of an intermediary or "primed"
      state of myeloid differentiation is associated with increased H4 arginine 3 and
      decreased H3 lysine 4 methylation. These modifications occur before transcription
      and appear to prime the chromatin for subsequent hormone-regulated transcription.
      Moreover, inhibition of methyltransferase activity, pre-acetylation, or
      activation of the enzyme PAD4 attenuated retinoid-regulated gene expression,
      while overexpression of PRMT1, a methyltransferase, enhanced retinoid
      responsiveness. Taken together, our results suggest that H4 arginine 3
      methylation is a bona fide positive epigenetic marker and regulator of
      transcriptional responsiveness as well as a signal integration mechanism during
      cell differentiation and, as such, may provide epigenetic memory.

PMID- 15964821
TI  - Centrin 2 stimulates nucleotide excision repair by interacting with xeroderma
      pigmentosum group C protein.
AB  - Xeroderma pigmentosum group C (XPC) protein plays a key role in DNA damage
      recognition in global genome nucleotide excision repair (NER). The protein forms
      in vivo a heterotrimeric complex involving one of the two human homologs of
      Saccharomyces cerevisiae Rad23p and centrin 2, a centrosomal protein. Because
      centrin 2 is dispensable for the cell-free NER reaction, its role in NER has been
      unclear. Binding experiments with a series of truncated XPC proteins allowed the
      centrin 2 binding domain to be mapped to a presumed alpha-helical region near the
      C terminus, and three amino acid substitutions in this domain abrogated
      interaction with centrin 2. Human cell lines stably expressing the mutant XPC
      protein exhibited a significant reduction in global genome NER activity.
      Furthermore, centrin 2 enhanced the cell-free NER dual incision and damaged DNA
      binding activities of XPC, which likely require physical interaction between XPC
      and centrin 2. These results reveal a novel vital function for centrin 2 in NER,
      the potentiation of damage recognition by XPC.

PMID- 15964822
TI  - Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von
      Hippel-Lindau-associated renal cell carcinoma.
AB  - Defective function of the von Hippel-Lindau (VHL) tumor suppressor ablates
      proteolytic regulation of hypoxia-inducible factor alpha subunits (HIF-1alpha and
      HIF-2alpha), leading to constitutive activation of hypoxia pathways in renal cell
      carcinoma (RCC). Here we report a comparative analysis of the functions of HIF
      1alpha and HIF-2alpha in RCC and non-RCC cells. We demonstrate common patterns of
      HIF-alpha isoform transcriptional selectivity in VHL-defective RCC that show
      consistent and striking differences from patterns in other cell types. We also
      show that HIF-alpha isoforms display unexpected suppressive interactions in RCC
      cells, with enhanced expression of HIF-2alpha suppressing HIF-1alpha and vice
      versa. In VHL-defective RCC cells, we demonstrate that the protumorigenic genes
      encoding cyclin D1, transforming growth factor alpha, and vascular endothelial
      growth factor respond specifically to HIF-2alpha and that the proapoptotic gene
      encoding BNip3 responds positively to HIF-1alpha and negatively to HIF-2alpha,
      indicating that HIF-1alpha and HIF-2alpha have contrasting properties in the
      biology of RCC. In keeping with this, HIF-alpha isoform-specific transcriptional
      selectivity was matched by differential effects on the growth of RCC as tumor
      xenografts, with HIF-1alpha retarding and HIF-2alpha enhancing tumor growth.
      These findings indicate that therapeutic approaches to targeting of the HIF
      system, at least in this setting, will need to take account of HIF isoform
      specific functions.

PMID- 15964823
TI  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for
      branching morphogenesis in the chorioallantoic placenta.
AB  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a membrane
      associated Kunitz-type serine proteinase inhibitor that was initially identified
      as a potent inhibitor of hepatocyte growth factor activator. HAI-1 is also a
      cognate inhibitor of matriptase, a membrane-associated serine proteinase. HAI-1
      is expressed predominantly in epithelial cells in the human body. Its mRNA is
      also abundant in human placenta, with HAI-1 specifically expressed by villous
      cytotrophoblasts. In order to address the precise roles of HAI-1 in vivo, we
      generated HAI-1 mutant mice by homozygous recombination. Heterozygous HAI-1+/-
      mice underwent normal organ development. However, homozygous HAI-1-/- mice
      experienced embryonic lethality which became evident at embryonic day 10.5
      postcoitum (E10.5). As early as E9.5, HAI-1-/- embryos showed growth retardation
      that did not reflect impaired cell proliferation but resulted instead from failed
      placental development and function. Histological analysis revealed severely
      impaired formation of the labyrinth layer, in contrast all other placental
      layers, such as the spongiotrophoblast layer and giant cell layer, which were
      formed. Our results indicate that mouse HAI-1 is essential for branching
      morphogenesis in the chorioallantoic placenta and lack of HAI-1 function may
      result in placental failure.

PMID- 15964824
TI  - Transcription factor KLF7 is important for neuronal morphogenesis in selected
      regions of the nervous system.
AB  - The Kruppel-like transcription factors (KLFs) are important regulators of cell
      proliferation and differentiation in several different organ systems. The mouse
      Klf7 gene is strongly active in postmitotic neuroblasts of the developing nervous
      system, and the corresponding protein stimulates transcription of the cyclin
      dependent kinase inhibitor p21waf/cip gene. Here we report that loss of KLF7
      activity in mice leads to neonatal lethality and a complex phenotype which is
      associated with deficits in neurite outgrowth and axonal misprojection at
      selected anatomical locations of the nervous system. Affected axon pathways
      include those of the olfactory and visual systems, the cerebral cortex, and the
      hippocampus. In situ hybridizations and immunoblots correlated loss of KLF7
      activity in the olfactory epithelium with significant downregulation of the
      p21waf/cip and p27kip1 genes. Cotransfection experiments extended the last
      finding by documenting KLF7's ability to transactivate a reporter gene construct
      driven by the proximal promoter of p27kip1. Consistent with emerging evidence for
      a role of Cip/Kip proteins in cytoskeletal dynamics, we also documented
      p21waf/cip and p27kip1 accumulation in the cytoplasm of differentiating olfactory
      sensory neurons. KLF7 activity might therefore control neuronal morphogenesis in
      part by optimizing the levels of molecules that promote axon outgrowth.

PMID- 15964825
TI  - Coactivator recruitment is essential for liganded thyroid hormone receptor to
      initiate amphibian metamorphosis.
AB  - Thyroid hormone receptors (TRs) can repress or activate target genes depending on
      the absence or presence of thyroid hormone (T3), respectively. This hormone
      dependent gene regulation is mediated by recruitment of co-repressors in the
      absence of T3 and coactivators in its presence. Many TR-interacting coactivators
      have been characterized in vitro. In comparison, few studies have addressed the
      developmental roles of these cofactors in vivo. We have investigated the role of
      coactivators in transcriptional activation by TR during postembryonic tissue
      remodeling by using amphibian metamorphosis as a model system. We have previously
      shown that steroid receptor coactivator 3 (SRC3) is expressed and upregulated
      during metamorphosis, suggesting a role in gene regulation by liganded TR. Here,
      we have generated transgenic tadpoles expressing a dominant negative form of SRC3
      (F-dnSRC3). The transgenic tadpoles exhibited normal growth and development
      throughout embryogenesis and premetamorphic stages. However, transgenic
      expression of F-dnSRC3 inhibits essentially all aspects of T3-induced
      metamorphosis, as well as natural metamorphosis, leading to delayed or arrested
      metamorphosis or the formation of tailed frogs. Molecular analysis revealed that
      F-dnSRC3 functioned by blocking the recruitment of endogenous coactivators to T3
      target genes without affecting corepressor release, thereby preventing the T3
      dependent gene regulation program responsible for tissue transformations during
      metamorphosis. Our studies thus demonstrate that coactivator recruitment, aside
      from corepressor release, is required for T3 function in development and further
      provide the first example where a specific coactivator-dependent gene regulation
      pathway by a nuclear receptor has been shown to underlie specific developmental
      events.

PMID- 15964826
TI  - Akt/protein kinase B-dependent phosphorylation and inactivation of WEE1Hu promote
      cell cycle progression at G2/M transition.
AB  - The serine/threonine kinase Akt is known to promote cell growth by regulating the
      cell cycle in G1 phase through activation of cyclin/Cdk kinases and inactivation
      of Cdk inhibitors. However, how the G2/M phase is regulated by Akt remains
      unclear. Here, we show that Akt counteracts the function of WEE1Hu. Inactivation
      of Akt by chemotherapeutic drugs or the phosphatidylinositide-3-OH kinase
      inhibitor LY294002 induced G2/M arrest together with the inhibitory
      phosphorylation of Cdc2. Because the increased Cdc2 phosphorylation was
      completely suppressed by wee1hu gene silencing, WEE1Hu was associated with G2/M
      arrest induced by Akt inactivation. Further analyses revealed that Akt directly
      bound to and phosphorylated WEE1Hu during the S to G2 phase. Serine-642 was
      identified as an Akt-dependent phosphorylation site. WEE1Hu kinase activity was
      not affected by serine-642 phosphorylation. We revealed that serine-642
      phosphorylation promoted cytoplasmic localization of WEE1Hu. The nuclear-to
      cytoplasmic translocation was mediated by phosphorylation-dependent WEE1Hu
      binding to 14-3-3theta but not 14-3-3beta or -sigma. These results indicate that
      Akt promotes G2/M cell cycle progression by inducing phosphorylation-dependent 14
      3-3theta binding and cytoplasmic localization of WEE1Hu.

PMID- 15964827
TI  - Srs2 and Sgs1 DNA helicases associate with Mre11 in different subcomplexes
      following checkpoint activation and CDK1-mediated Srs2 phosphorylation.
AB  - Mutations in the genes encoding the BLM and WRN RecQ DNA helicases and the MRE11
      RAD50-NBS1 complex lead to genome instability and cancer predisposition
      syndromes. The Saccharomyces cerevisiae Sgs1 RecQ helicase and the Mre11 protein,
      together with the Srs2 DNA helicase, prevent chromosome rearrangements and are
      implicated in the DNA damage checkpoint response and in DNA recombination. By
      searching for Srs2 physical interactors, we have identified Sgs1 and Mre11. We
      show that Srs2, Sgs1, and Mre11 form a large complex, likely together with yet
      unidentified proteins. This complex reorganizes into Srs2-Mre11 and Sgs1-Mre11
      subcomplexes following DNA damage-induced activation of the Mec1 and Tel1
      checkpoint kinases. The defects in subcomplex formation observed in mec1 and tel1
      cells can be recapitulated in srs2-7AV mutants that are hypersensitive to intra-S
      DNA damage and are altered in the DNA damage-induced and Cdk1-dependent
      phosphorylation of Srs2. Altogether our observations indicate that Mec1- and Tel1
      dependent checkpoint pathways modulate the functional interactions between Srs2,
      Sgs1, and Mre11 and that the Srs2 DNA helicase represents an important target of
      the Cdk1-mediated cellular response induced by DNA damage.

PMID- 15964828
TI  - Ligand-induced partitioning of human CXCR1 chemokine receptors with lipid raft
      microenvironments facilitates G-protein-dependent signaling.
AB  - Ligand binding to a chemokine receptor triggers signaling events through
      heterotrimeric G-proteins. The mechanisms underlying receptor-mediated G-protein
      activation in the heterogeneous microenvironments of the plasma membrane are
      unclear. Here, using live-cell fluorescence resonance energy transfer imaging to
      detect the proximity between CXCR1-cyan fluorescent protein (CFP) and
      fluorescence probes that label lipid raft or non-lipid raft microdomains and
      using fluorescence recovery after photobleaching analysis to measure the lateral
      diffusion of CXCR1-CFP, we found that interleukin-8 induces association between
      the receptors and lipid raft microenvironments. Disruption of lipid rafts
      impaired G-protein-dependent signaling, such as Ca2+ responses and
      phosphatidylinositol 3-kinase activation, but had no effect on ligand-binding
      function and did not completely abolish ligand-induced receptor phosphorylation.
      Our results suggest a novel mechanism by which ligand binding to CXCR1 promotes
      lipid raft partitioning of receptors and facilitates activation of heterotrimeric
      G-proteins.

PMID- 15964829
TI  - Generation and characterization of Rac3 knockout mice.
AB  - Rac proteins are members of the Rho family of GTPases involved in the regulation
      of actin dynamics. The three highly homologous Rac proteins in mammals are the
      ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized
      Rac3. We show here that Rac3 mRNA is widely and specifically expressed in the
      developing nervous system, with highest concentration at embryonic day 13 in the
      dorsal root ganglia and ventral spinal cord. At postnatal day 7 Rac3 appears
      particularly abundant in populations of projection neurons in several regions of
      the brain, including the fifth layer of the cortex and the CA1-CA3 region of the
      hippocampus. We generated mice deleted for the Rac3 gene with the aim of
      analyzing the function of this GTPase in vivo. Rac3 knockout animals survive
      embryogenesis and show no obvious developmental defects. Interestingly, specific
      behavioral differences were detected in the Rac3-deficient animals, since motor
      coordination and motor learning on the rotarod was superior to that of their wild
      type littermates. No obvious histological or immunohistological differences were
      observed at major sites of Rac3 expression. Our results indicate that, in vivo,
      Rac3 activity is not strictly required for normal development in utero but may be
      relevant to later events in the development of a functional nervous system.

PMID- 15964831
TI  - Fibronectin's central cell-binding domain supports focal adhesion formation and
      Rho signal transduction.
AB  - Fibroblast adhesion to fibronectin (FN) induces formation of focal adhesions
      (FAs), structures that have significant effect on cell migration and signaling.
      FA formation requires actomyosin-based contractility that is regulated by Rho
      dependent myosin light chain (MLC) phosphorylation. Previous studies indicated
      that the FN central cell-binding (and integrin-binding) domain (CBD) is
      insufficient for FA formation and that the major heparin-binding domain (HepII)
      facilitates FA formation in a Rho-dependent manner. We describe here conditions
      under which FN CBD alone is sufficient for FA formation in both human dermal
      fibroblasts and the FN-null murine fibroblasts. CBD-mediated FA formation is
      dependent on its surface adsorption and the adhesion activity of the cells.
      Attachment of FN-null fibroblasts to CBD elicits the same biphasic regulation of
      Rho activity as seen on intact FN, whereas adhesion to HepII alone does not
      activate Rho. Activation of Rho requires high levels of integrin occupancy.
      However, FN or CBD may induce FAs without increased activation of Rho (i.e. the
      basal level of GTP-Rho induces sufficient phospho-MLC for FA assembly under this
      condition). In contrast, adhesion to HepII alone does not sustain MLC
      phosphorylation. Pulse stimulation of cells on CBD or HepII with lysophosphatidic
      acid elevates Rho GTP loading to the same level, but the lysophosphatidic acid
      stimulated MLC phosphorylation is significantly lower in cells on HepII than on
      CBD. Coating HepII with suboptimal concentrations of CBD induces FAs without
      increased activation of Rho. Therefore, FN CBD can support FA formation and
      generate contraction by activating Rho or by facilitating Rho downstream
      signaling.

PMID- 15964830
TI  - Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic
      leukemia.
AB  - Numerous studies indirectly implicate Rac GTPases in cancer. To investigate if
      Rac3 contributes to normal or malignant cell function, we generated rac3 null
      mutants through gene targeting. These mice were viable, fertile, and lacked an
      obvious external phenotype. This shows Rac3 function is dispensable for embryonic
      development. Bcr/Abl is a deregulated tyrosine kinase that causes chronic
      myelogenous leukemia and Ph-positive acute lymphoblastic leukemia in humans.
      Vav1, a hematopoiesis-specific exchange factor for Rac, was constitutively
      tyrosine phosphorylated in primary lymphomas from Bcr/Abl P190 transgenic mice,
      suggesting inappropriate Rac activation. rac3 is expressed in these malignant
      hematopoietic cells. Using lysates from BCR/ABL transgenic mice that express or
      lack rac3, we detected the presence of activated Rac3 but not Rac1 or Rac2 in the
      malignant precursor B-lineage lymphoblasts. In addition, in female P190 BCR/ABL
      transgenic mice, lack of rac3 was associated with a longer average survival.
      These data are the first to directly show a stimulatory role for Rac in leukemia
      in vivo. Moreover, our data suggest that interference with Rac3 activity, for
      example, by using geranyl-geranyltransferase inhibitors, may provide a positive
      clinical benefit for patients with Ph-positive acute lymphoblastic leukemia.

PMID- 15964833
TI  - DNA joint dependence of pol X family polymerase action in nonhomologous end
      joining.
AB  - DNA double strand breaks (DSBs) can be rejoined directly by the nonhomologous end
      joining (NHEJ) pathway of repair. Nucleases and polymerases are required to
      promote accurate NHEJ when the terminal bases of the DSB are damaged. The same
      enzymes also participate in imprecise rejoining and joining of incompatible ends,
      important mutagenic events. Previous work has shown that the Pol X family
      polymerase Pol4 is required for some but not all NHEJ events that require gap
      filling in Saccharomyces cerevisiae. Here, we systematically analyzed DSB end
      configurations and found that gaps on both strands and overhang polarity are the
      principal factors that determine whether a joint requires Pol4. DSBs with 3'
      overhangs and a gap on each strand strongly depended on Pol4 for repair, DSBs
      with 5'-overhangs of the same sequence did not. Pol4 was not required when 3'
      overhangs contained a gap on only one strand, however. Pol4 was equally required
      at 3'-overhangs of all lengths within the NHEJ-dependent range but was
      dispensable outside of this range, indicating that Pol4 is specific to NHEJ. Loss
      of Pol4 did not affect the rejoining of DSBs that utilized a recessed
      microhomology or DSBs bearing 5'-hydroxyls but no gap. Finally, mammalian Pol X
      polymerases were able to differentially complement a pol4 mutation depending on
      the joint structure, demonstrating that these polymerases can participate in
      yeast NHEJ but with distinct properties.

PMID- 15964832
TI  - Global loss of Set1-mediated H3 Lys4 trimethylation is associated with silencing
      defects in Saccharomyces cerevisiae.
AB  - Post-translational histone modifications, such as acetylation, phosphorylation,
      ubiquitination, and methylation, have been correlated with regulation of gene
      expression. In Saccharomyces cerevisiae, Set1 has been identified as the sole
      histone methyltransferase required for histone H3 lysine 4 (Lys(4)) methylation.
      Yeast cells that do not express Set1 have several apparent phenotypes, including
      slow growth and defects in telomere, HML, and rDNA silencing. However, the
      mechanism by which the Set1 methyltransferase mediates differential histone H3
      methylation (mono-, di-, and tri-) is still not understood, and the involvement
      of domains or regions in Set1 contributing to H3 Lys(4) methylation has not been
      well characterized. In this study, the N terminus of Set1 was shown to be
      important for global and gene specific histone H3 trimethylation. We show that
      Set1 trimethyl-defective mutants can rescue a set1Delta slow growth defect. In
      contrast, Set1 trimethyl mutants were defective in telomere, rDNA, HML, and HMR
      silencing. Taken together, these data suggest that histone H3 Lys(4)
      trimethylation is required for proper silencing, while mono- and/or dimethylation
      is sufficient for cell growth.

PMID- 15964834
TI  - Hoxb13 up-regulates transglutaminase activity and drives terminal differentiation
      in an epidermal organotypic model.
AB  - Hox genes act to differentiate and pattern embryonic structures by promoting the
      proliferation of specific cell types. An exception is Hoxb13, which functions as
      a proapoptotic and antiproliferative protein during development of the caudal
      spinal cord and tail vertebrae and has also been implicated in adult cutaneous
      wound repair. The adult epidermis, which expresses several Hox genes including
      Hoxb13, is continually renewed in a program of growth arrest, differentiation,
      and a specialized form of apoptosis (cornification). Yet little is known about
      the function(s) of these genes in skin. Based on its role during embryogenesis,
      Hoxb13 is an attractive candidate to be involved in the regulation of epidermal
      differentiation. Here, we demonstrate that Hoxb13 overexpression in an adult
      organotypic epidermal model recapitulates actions of Hoxb13 reported in embryonic
      development. Epidermal cell proliferation is decreased, apoptosis increased, and
      excessive terminal differentiation observed, as characterized by enhanced
      transglutaminase activity and excessive cornified envelope formation.
      Overexpression of Hoxb13 also produces abnormal phenotypes in the epidermal
      tissue that resemble certain pathological features of dysplastic skin diseases.
      Our results suggest that Hoxb13 functions to promote epidermal differentiation, a
      critical process for skin regeneration and for the maintenance of normal barrier
      function.

PMID- 15964835
TI  - Saccharomyces cerevisiae DNA polymerase delta: high fidelity for base
      substitutions but lower fidelity for single- and multi-base deletions.
AB  - Eukaryotic DNA polymerase delta (Pol delta) plays an essential role in
      replicating large nuclear genomes, a process that must be accurate to maintain
      stability over many generations. Based on kinetic studies of insertion of
      individual dNTPs opposite a template guanine, Pol delta is believed to have high
      selectivity for inserting correct nucleotides. This high selectivity, in
      conjunction with an intrinsic 3'-exonuclease activity, implies that Pol delta
      should have high base substitution fidelity. Here we demonstrate that the wild
      type Saccharomyces cerevisiae three-subunit Pol delta does indeed have high base
      substitution fidelity for the 12 possible base-base mismatches, producing on
      average less than 1.3 stable misincorporations/100,000 nucleotides polymerized.
      Measurements with exonuclease-deficient Pol delta confirm the high nucleotide
      selectivity of the polymerase and further indicate that proofreading enhances the
      base substitution fidelity of the wild type enzyme by at least 60-fold. However,
      Pol delta inefficiently proofreads single nucleotide deletion mismatches in
      homopolymeric runs, such that the error rate is 30 single nucleotide
      deletions/100,000 nucleotides polymerized. Moreover, wild type Pol delta
      frequently deletes larger numbers of nucleotides between distantly spaced direct
      repeats of three or more base pairs. Although wild type Pol delta and Pol epsilon
      both have high base substitution fidelity, Pol delta is much less accurate than
      Pol epsilon for deletions involving repetitive sequences. Thus, strand slippage
      during replication by wild type Pol delta may be a primary source of insertion
      and deletion mutagenesis in eukaryotic genomes.

PMID- 15964836
TI  - A PHD finger motif in the C terminus of RAG2 modulates recombination activity.
AB  - The RAG1 and RAG2 proteins catalyze V(D)J recombination and are essential for
      generation of the diverse repertoire of antigen receptor genes and effective
      immune responses. RAG2 is composed of a "core" domain that is required for the
      recombination reaction and a C-terminal nonessential or "non-core" region. Recent
      evidence has emerged arguing that the non-core region plays a critical regulatory
      role in the recombination reaction, and mutations in this region have been
      identified in patients with immunodeficiencies. Here we present the first
      structural data for the RAG2 protein, using NMR spectroscopy to demonstrate that
      the C terminus of RAG2 contains a noncanonical PHD finger. All of the non-core
      mutations of RAG2 that are implicated in the development of immunodeficiencies
      are located within the PHD finger, at either zinc-coordinating residues or
      residues adjacent to an alpha-helix on the surface of the domain that
      participates in binding to the signaling molecules, phosphoinositides. Functional
      analysis of disease and phosphoinositide-binding mutations reveals novel
      intramolecular interactions within the non-core region and suggests that the PHD
      finger adopts two distinct states. We propose a model in which the equilibrium
      between these states modulates recombination activity. Together, these data
      identify the PHD finger as a novel and functionally important domain of RAG2.

PMID- 15964837
TI  - Multiple turnover transfer of [2Fe2S] clusters by the iron-sulfur cluster
      assembly scaffold proteins IscU and IscA.
AB  - IscU/Isu and IscA/Isa (and related NifU and SufA proteins) have been proposed to
      serve as molecular scaffolds for preassembly of [FeS] clusters to be used in the
      biogenesis of iron-sulfur proteins. In vitro studies demonstrating transfer of
      preformed scaffold-[FeS] complexes to apoprotein acceptors have provided
      experimental support for this hypothesis, but investigations to date have yielded
      only single-cluster transfer events. We describe an in vitro assay system that
      allows for real-time monitoring of [FeS] cluster formation using circular
      dichroism spectroscopy and use this to investigate de novo [FeS] cluster
      formation and transfer from Escherichia coli IscU and IscA to apo-ferredoxin.
      Both IscU and IscA were found to be capable of multiple cycles of [2Fe2S] cluster
      formation and transfer suggesting that these scaffold proteins are capable of
      acting "catalytically." Kinetic studies further showed that cluster transfer
      exhibits Michaelis-Menten behavior indicative of complex formation of holo-IscU
      and holo-IscA with apoferredoxin and consistent with a direct [FeS] cluster
      transfer mechanism. Analysis of the dependence of the rate of cluster transfer,
      however, revealed enhanced efficiency at low ratios of scaffold to acceptor
      protein suggesting participation of a transient, labile scaffold-[FeS] species in
      the transfer process.

PMID- 15964838
TI  - Glycosylation of Eag1 (Kv10.1) potassium channels: intracellular trafficking and
      functional consequences.
AB  - N-Linked glycosylation is a common post-translational modification of membrane
      proteins. Here we report that mature Eag1 potassium channels carry sugar moieties
      linked to asparagines at positions 388 and 406. Asn-388 seems to undergo only
      core glycosylation, but complex sugars are bound to Asn-406. Correct complex
      glycosylation is required for proper trafficking of Eag1 to the plasma membrane
      but is also crucial for the correct function of channels already inserted in the
      membrane.

PMID- 15964839
TI  - Structural basis for autoinhibition and mutational activation of eukaryotic
      initiation factor 2alpha protein kinase GCN2.
AB  - The GCN2 protein kinase coordinates protein synthesis with levels of amino acid
      stores by phosphorylating eukaryotic translation initiation factor 2. The
      autoinhibited form of GCN2 is activated in cells starved of amino acids by
      binding of uncharged tRNA to a histidyl-tRNA synthetase-like domain. Replacement
      of Arg-794 with Gly in the PK domain (R794G) activates GCN2 independently of tRNA
      binding. Crystal structures of the GCN2 protein kinase domain have been
      determined for wild-type and R794G mutant forms in the apo state and bound to
      ATP/AMPPNP. These structures reveal that GCN2 autoinhibition results from
      stabilization of a closed conformation that restricts ATP binding. The R794G
      mutant shows increased flexibility in the hinge region connecting the N- and C
      lobes, resulting from loss of multiple interactions involving Arg794. This
      conformational change is associated with intradomain movement that enhances ATP
      binding and hydrolysis. We propose that intramolecular interactions following
      tRNA binding remodel the hinge region in a manner similar to the mechanism of
      enzyme activation elicited by the R794G mutation.

PMID- 15964840
TI  - Evidence for a granule targeting sequence within platelet factor 4.
AB  - Platelets achieve bleeding arrest at sites of vascular injury via secretion of
      secretory proteins from their storage granules, termed alpha-granules. We have
      recently analyzed granule targeting of platelet factor 4 (PF4), a secretory alpha
      granule chemokine, and demonstrated that PF4 alpha-granule storage relied upon
      determinants within PF4 mature sequence. To define these determinants, PF4
      mutants fused to the fluorescent reporter protein green fluorescent protein were
      generated by progressive deletions and site-directed mutagenesis. They were then
      transfected in AtT20 cells and assessed for granule targeting by colocalization
      with ACTH-containing granules, using laser scanning confocal microscopy. This
      strategy identified the amino acid 41-50 (LIATLKNGRK) sequence as most critical
      for PF4 granule targeting and/or storage; its deletion from PF4 induced a marked
      decrease in granule storage (from 81 +/- 2% to 17 +/- 3%, p < or = 0.0001). Ala
      scanning mutagenesis of LIATLKNGRK narrowed down the targeting motif to LKNG. A
      direct role for LKNG in alpha-granule targeting was confirmed in the
      thrombopoietin-induced human megakaryocytic Dami cells, in which the LKNG-green
      fluorescent protein chimera exhibited an 82.5 +/- 1.8% colocalization with the
      alpha-granule proteins von Willebrand factor and P-selectin. LKNG is poorly
      conserved within the chemokine family. However three-dimensional alignments of
      the human alpha-granule chemokines Nap-2 (neutrophil-activating peptide) and
      RANTES (Regulated upon Activation Normal T Cell Expressed and Secreted) with PF4
      revealed that LKNG, a surface-exposed hydrophilic turn/loop, matched Nap-2 (LKDG)
      and RANTES (TRKN) peptides with similar features. Moreover Nap-2 and RANTES
      peptides exhibited the same alpha-granule targeting efficiency than LKNG. We
      therefore postulate that the three-dimensional and physicochemical
      characteristics of PF4 LKNG are of general relevance to alpha-granule targeting
      of chemokines and possibly of other alpha-granule proteins.

PMID- 15964841
TI  - MyD88 is pivotal for the early inflammatory response and subsequent bacterial
      clearance and survival in a mouse model of Chlamydia pneumoniae pneumonia.
AB  - Chlamydia pneumoniae is the causative agent of respiratory tract infections and a
      number of chronic diseases. Here we investigated the involvement of the common
      TLR adaptor molecule MyD88 in host responses to C. pneumoniae-induced pneumonia
      in mice. MyD88-deficient mice were severely impaired in their ability to mount an
      acute early inflammatory response toward C. pneumoniae. Although the bacterial
      burden in the lungs was comparable 5 days after infection, MyD88-deficient mice
      exhibited only minor signs of pneumonia and reduced expression of inflammatory
      mediators. MyD88-deficient mice were unable to up-regulate proinflammatory
      cytokines and chemokines, demonstrated delayed recruitment of CD8+ and CD4+ T
      cells to the lungs, and were unable to clear the pathogen from their lungs at day
      14. At day 14 the MyD88-deficent mice developed a severe, chronic lung
      inflammation with elevated IL-1beta and IFN-gamma leading to increased mortality,
      whereas wild-type mice as well as TLR2- or TLR4-deficient mice recovered from
      acute pneumonia and did not show delayed bacterial clearance. Thus, MyD88 is
      essential to recognize C. pneumoniae infection and initiate a prompt and
      effective immune host response against this organism leading to clearance of
      bacteria from infected lungs.

PMID- 15964842
TI  - Structural organization and Zn2+-dependent subdomain interactions involving
      autoantigenic epitopes in the Ring-B-box-coiled-coil (RBCC) region of Ro52.
AB  - Ro52 is one of the major autoantigens targeted in the autoimmune disease Sjogren
      syndrome. By sequence similarity, Ro52 belongs to the RING-B-box-coiled-coil
      (RBCC) protein family. Disease-related antibodies bind Ro52 in a conformation
      dependent way both in the coiled-coil region and in the Zn2+-binding Ring-B-box
      region. Primarily associated with Sjogren syndrome, Ro52 autoantibodies directed
      to a specific, partially structured epitope in the coiled-coil region may also
      induce a congenital heart block in the fetus of pregnant Ro52-positive mothers.
      To improve our understanding of the pathogenic effects of autoantibody binding to
      the Zn2+-binding region, a multianalytical mapping of its structural,
      biophysical, and antigenic properties is presented. Structure content and ligand
      binding of subregions, dissected by peptide synthesis and subcloning, were
      analyzed by fluorescence and circular dichroism spectroscopy. A novel matrix
      assisted laser desorption ionization time-of-flight mass spectrometry strategy
      for time-resolved proteolysis experiments of large protein domains was developed
      to facilitate analysis and to help resolve the tertiary arrangement of the entire
      RBCC subregion. The linker region between the RING and B-box motifs is crucial
      for full folding, and Zn2+ affinity of the RING-B-box region is further protected
      in the entire RBCC region and appears to interact with the coiled-coil region.
      Murine monoclonal antibodies raised toward the RING-B-box region were primarily
      directed toward the linker, further supporting a highly functional role for the
      linker in a cellular environment. Taken together with our previous analysis of
      autoantigenic epitopes in the coiled-coil region, localization of autoantigenic
      epitopes in Ro52 appears closely related to molecular functionalities.

PMID- 15964843
TI  - The conformation, location, and dynamic properties of the endocannabinoid ligand
      anandamide in a membrane bilayer.
AB  - The endogenous cannabinoid ligand anandamide is biosynthesized from membrane
      phospholipid precursors and is believed to reach its sites of action on the CB1
      and CB2 receptors through fast lateral diffusion within the cell membrane. To
      gain a better insight on the stereochemical features of its association with the
      cell membrane and its interaction with the cannabinoid receptors, we have studied
      its conformation, location, and dynamic properties in a
      dipalmitoylphosphatidylcholine multilamellar model membrane bilayer system. By
      exploiting the bilayer lattice as an internal three-dimensional reference grid,
      the conformation and location of anandamide were determined by measuring selected
      inter- and intramolecular distances between strategically introduced isotopic
      labels using the rotational echo double resonance (REDOR) NMR method. A molecular
      model was proposed to represent the structural features of our anandamide/lipid
      system and was subsequently used in calculating the multispin dephasing curves.
      Our results demonstrate that anandamide adopts an extended conformation within
      the membrane with its headgroup at the level of the phospholipid polar group and
      its terminal methyl group near the bilayer center. Parallel static (2)H NMR
      experiments further confirmed these findings and provided evidence that
      anandamide experiences dynamic properties similar to those of the membrane
      phospholipids and produces no perturbation to the bilayer. Our results are
      congruent with a hypothesis that anandamide approaches its binding site by
      laterally diffusing within one membrane leaflet in an extended conformation and
      interacts with a hydrophobic groove formed by helices 3 and 6 of CB1, where its
      terminal carbon is positioned close to a key cysteine residue in helix 6 leading
      to receptor activation.

PMID- 15964844
TI  - Induction of NR4A orphan nuclear receptor expression in macrophages in response
      to inflammatory stimuli.
AB  - Oxidized lipids and inflammatory cytokines are believed to play a causal role in
      atherosclerosis through the regulation of gene expression in macrophages and
      other cells. Previous work has implicated the nuclear receptors peroxisome
      proliferator-activated receptor and liver X receptor in the control of lipid
      dependent gene expression and inflammation. Here we demonstrate that expression
      of a third group of nuclear receptors, the NR4A ligand-independent orphan
      receptors, is highly inducible in macrophages by diverse inflammatory stimuli.
      Treatment of macrophages with lipopolysaccharide (LPS), cytokines, or oxidized
      lipids triggers the transcriptional induction of Nur77 (NR4A1), Nurr1 (NR4A2),
      and NOR1 (NR4A3) expression. Several lines of evidence point to the NF-kappaB
      signaling pathway as a principal mediator of inducible NR4A expression in
      macrophages. Analysis of the murine and human Nur77 promoters revealed two highly
      conserved NF-kappaB response elements. Mutation of these elements inhibited LPS
      dependent expression of the Nur77 promoter in transient transfection assays.
      Furthermore, induction of Nur77 expression by LPS was severely compromised in
      fibroblasts lacking the three NF-kappaB subunits, Nfkb1, c-Rel, and RelA.
      Consistent with its ability to be induced by oxidized lipids, Nur77 was expressed
      in macrophages within human atherosclerotic lesions. These results identified
      NR4A nuclear receptors as potential transcriptional mediators of inflammatory
      signals in activated macrophages.

PMID- 15964845
TI  - Mutant protein kinase Cgamma found in spinocerebellar ataxia type 14 is
      susceptible to aggregation and causes cell death.
AB  - Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative
      disease characterized by various symptoms including cerebellar ataxia. Recently,
      several missense mutations in the protein kinase Cgamma (gammaPKC) gene have been
      found in different SCA14 families. To elucidate how the mutant gammaPKC causes
      SCA14, we examined the molecular properties of seven mutant (H101Y, G118D, S119P,
      S119F, Q127R, G128D, and F643L) gammaPKCs fused with green fluorescent protein
      (gammaPKC-GFP). Wild-type gammaPKC-GFP was expressed ubiquitously in the
      cytoplasm of CHO cells, whereas mutant gammaPKC-GFP tended to aggregate in the
      cytoplasm. The insolubility of mutant gammaPKC-GFP to Triton X-100 was increased
      and correlated with the extent of aggregation. gammaPKC-GFP in the Triton
      insoluble fraction was rarely phosphorylated at Thr(514), whereas gammaPKC-GFP in
      the Triton-soluble fraction was phosphorylated. Furthermore, the stimulation of
      the P2Y receptor triggered the rapid aggregation of mutant gammaPKC-GFP within 10
      min after transient translocation to the plasma membrane. Overexpression of the
      mutant gammaPKC-GFP caused cell death that was more prominent than wild type. The
      cytotoxicity was exacerbated in parallel with the expression level of the mutant.
      These results indicate that SCA14 mutations make gammaPKC form cytoplasmic
      aggregates, suggesting the involvement of this property in the etiology of SCA14.

PMID- 15964846
TI  - SET8 recognizes the sequence RHRK20VLRDN within the N terminus of histone H4 and
      mono-methylates lysine 20.
AB  - Methylation of lysine 20 in histone H4 has been proven to play important roles in
      chromatin structure and gene regulation. SET8 is one of the methyltransferases
      identified to be specific for this modification. In this study, the minimal
      active SET domain of SET8 has been mapped to the region of amino acids 195-352.
      This region completely retains the same methylation activity and substrate
      specificity as the full-length SET8. The SET domain recognizes a stretch of
      specific amino acid sequence around lysine 20 of H4 for its methylation activity.
      Methylation assays with N terminus mutants of H4 that contain deletions and
      single alanine or glutamine substitutions of charged residues revealed that SET8
      requires the sequence RHRK20VLRDN for methylation at lysine 20. The individual
      mutation of any charged residue in this sequence to alanine or glutamine
      abolished or greatly decreased levels of methylation of lysine 20 of H4 by SET8.
      Interestingly, mutation of lysine 16 to alanine, arginine, glutamine, or
      methionine did not affect methylation of lysine 20 by the SET domain. Mass
      spectrometric analysis of synthesized H4 N-terminal peptides modified by SET8
      showed that SET8 selectively mono-methylates lysine 20 of H4. Taken together, our
      results suggested that the coordination between the amino acid sequence
      RHRK20VLRDN and the SET domain of SET8 determines the substrate specificity and
      multiplicity of methylation of lysine 20 of H4.

PMID- 15964847
TI  - Structure of the chromo barrel domain from the MOF acetyltransferase.
AB  - We report here the structure of the putative chromo domain from MOF, a member of
      the MYST family of histone acetyltransferases that acetylates histone H4 at Lys
      16 and is part of the dosage compensation complex in Drosophila. We found that
      the structure of this domain is a beta-barrel that is distinct from the alpha +
      beta fold of the canonical chromo domain. Despite the differences, there are
      similarities that support an evolutionary relationship between the two domains,
      and we propose the name "chromo barrel." The chromo barrel domains may be divided
      into two groups, MSL3-like and MOF-like, on the basis of whether a group of
      conserved aromatic residues is present or not. The structure suggests that,
      although the MOF-like domains may have a role in RNA binding, the MSL3-like
      domains could instead bind methylated residues. The MOF chromo barrel shares a
      common fold with other chromatin-associated modules, including the MBT-like
      repeat, Tudor, and PWWP domains. This structural similarity suggests a probable
      evolutionary pathway from these other modules to the canonical chromo domains (or
      vice versa) with the chromo barrel domain representing an intermediate structure.

PMID- 15964848
TI  - Activation of ataxia telangiectasia-mutated DNA damage checkpoint signal
      transduction elicited by herpes simplex virus infection.
AB  - Eukaryotic cells are equipped with machinery to monitor and repair damaged DNA.
      Herpes simplex virus (HSV) DNA replication occurs at discrete sites in nuclei,
      the replication compartment, where viral replication proteins cluster and
      synthesize a large amount of viral DNA. In the present study, HSV infection was
      found to elicit a cellular DNA damage response, with activation of the ataxia
      telangiectasia-mutated (ATM) signal transduction pathway, as observed by
      autophosphorylation of ATM and phosphorylation of multiple downstream targets
      including Nbs1, Chk2, and p53, while infection with a UV-inactivated virus or
      with a replication-defective virus did not. Activated ATM and the DNA damage
      sensor MRN complex composed of Mre11, Rad50, and Nbs1 were recruited and retained
      at sites of viral DNA replication, probably recognizing newly synthesized viral
      DNAs as abnormal DNA structures. These events were not observed in ATM-deficient
      cells, indicating ATM dependence. In Nbs1-deficient cells, HSV infection induced
      an ATM DNA damage response that was delayed, suggesting a functional MRN complex
      requirement for efficient ATM activation. However, ATM silencing had no effect on
      viral replication in 293T cells. Our data open up an interesting question of how
      the virus is able to complete its replication, although host cells activate ATM
      checkpoint signaling in response to the HSV infection.

PMID- 15964849
TI  - Extracellular matrix proteoglycans control the fate of bone marrow stromal cells.
AB  - Extracellular matrix glycoproteins and proteoglycans bind a variety of growth
      factors and cytokines thereby regulating matrix assembly as well as bone
      formation. However, little is known about the mechanisms by which extracellular
      matrix molecules modulate osteogenic stem cells and bone formation. Using mice
      deficient in two members of the small leucine-rich proteoglycans, biglycan and
      decorin, we uncovered a role for these two extracellular matrix proteoglycans in
      modulating bone formation from bone marrow stromal cells. Our studies showed that
      the absence of the critical transforming growth factor-beta (TGF-beta)-binding
      proteoglycans, biglycan and decorin, prevents TGF-beta from proper sequestration
      within the extracellular matrix. The excess TGF-beta directly binds to its
      receptors on bone marrow stromal cells and overactivates its signaling
      transduction pathway. Overall, the predominant effect of the increased TGF-beta
      signaling in bgn/dcn-deficient bone marrow stromal cells is a "switch in fate"
      from growth to apoptosis, leading to decreased numbers of osteoprogenitor cells
      and subsequently reduced bone formation. Thus, biglycan and decorin appear to be
      essential for maintaining an appropriate number of mature osteoblasts by
      modulating the proliferation and survival of bone marrow stromal cells. These
      findings underscore the importance of the micro-environment in controlling the
      fate of adult stem cells and reveal a novel cellular and molecular basis for the
      physiological and pathological control of bone mass.

PMID- 15964850
TI  - Identification of Ser153 in ICL2 of the gonadotropin-releasing hormone (GnRH)
      receptor as a phosphorylation-independent site for inhibition of Gq coupling.
AB  - Type I gonadotropin-releasing hormone (GnRH) receptor (GnRHR) is unique among
      mammalian G-protein-coupled receptors (GPCRs) in lacking a C-terminal tail, which
      is involved in desensitization in GPCRs. Therefore, we searched for inhibitory
      sites in the intracellular loops (ICLs) of the GnRHR. Synthetic peptides
      corresponding to the three ICLs were inserted into permeabilized alphaT3-1
      gonadotrope cells, and GnRH-induced inositol phosphate (InsP) formation was
      determined. GnRH-induced InsP production was potentiated by ICL2 > ICL3 but not
      by the ICL1 peptides, suggesting they are acting as decoy peptides. We examined
      the effects of six peptides in which only one of the Ser or Thr residues was
      substituted with Ala or Glu. Only substitution of Ser153 with Ala or Glu ablated
      the potentiating effect upon GnRH-induced InsP elevation. ERK activation was
      enhanced, and the rate of GnRH-induced InsP formation was about 6.5-fold higher
      in the first 10 min in COS-1 cells that were transfected with mutants of the
      GnRHR in which the ICL2 Ser/Thr residues (Ser151, Ser153, and Thr142) or only
      Ser153 was mutated to Ala as compared with the wild type GnRHR. The data indicate
      that ICL2 harbors an inhibitory domain, such that exogenous ICL2 peptide serves
      as a decoy for the inhibitory site (Ser153) of the GnRHR, thus enabling further
      activation. GnRH does not induce receptor phosphorylation in alphaT3-1 cells.
      Because the phosphomimetic ICL2-S153E peptide did not mimic the stimulatory
      effect of the ICL2 peptide, the inhibitory effect of Ser153 operates through a
      phosphorylation-independent mechanism.

PMID- 15964852
TI  - Cdk2-dependent Inhibition of p21 stability via a C-terminal cyclin-binding motif.
AB  - p21 is a member of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors
      that includes p21, p27, and p57. Recent studies have suggested that Cdk2 activity
      may promote p21 degradation through a pathway similar to that for p27, although
      the mechanism by which this occurs has not been clarified. In the current report,
      co-expression with cyclin E and Cdk2 stabilized p21 in a manner that required the
      CDK-binding site of p21 and a cyclin-binding site (cy1) located in the p21 N
      terminus. Strikingly, however, a kinase-dead Cdk2 mutant stabilized p21 to a
      greater extent than did wild-type Cdk2, consistent with the notion that Cdk2
      activity can destabilize p21. The ability of wild-type Cdk2 to destabilize p21
      required a potential Cdk2 phosphorylation site in p21 at serine 130 and an intact
      cyclin-binding motif (cy2) in the p21 C terminus. Finally, p21 was phosphorylated
      by Cdk2 at Ser-130 in vitro, and this ability of Cdk2 to phosphorylate p21 was
      dependent, in large part, on the presence of cy2. These results support a model
      in which active Cdk2 destabilizes p21 via the cy2 cyclin-binding motif and p21
      phosphorylation.

PMID- 15964851
TI  - Identification of the ankyrin repeat proteins ANKRA and RFXANK as novel partners
      of class IIa histone deacetylases.
AB  - Eighteen human histone deacetylases (HDACs) have been identified, and according
      to their sequence similarity to yeast homologs, these enzymes are grouped into
      distinct classes. Within class II, HDAC4, HDAC5, HDAC7, and HDAC9 share similar
      domain organization both within the N-terminal extension and the C-terminal
      catalytic domain, thus forming a subclass known as class IIa. These HDACs
      function as signal-responsive transcriptional corepressors. To gain further
      insight into their function and regulation, we utilized an N-terminal fragment of
      HDAC4 as bait in yeast two-hybrid screens, which uncovered myocyte enhancer
      factor 2C, 14-3-3zeta, and ankyrin repeat family A protein (ANKRA). ANKRA is a
      poorly characterized protein with an ankyrin repeat domain similar to RFXANK, a
      subunit of the trimeric transcription factor RFX. Mutations on genes of the RFX
      subunits and the coactivator CIITA are responsible for the bare lymphocyte
      syndrome, an immunodeficiency disorder attributed to the lack of major
      histocompatibility complex class II (MHCII) antigens. Through its ankyrin repeat
      domain, RFXANK interacted with HDAC4. Two RFXANK-binding sites were found on
      HDAC4 with one located within residues 118-279 and another within residues 448
      666. Interestingly, this deacetylase also interacted with CIITA. Consistent with
      the physical interaction with RFXANK and CIITA, HDAC4 and homologs repressed
      MHCII expression. These results identify ANKRA, RFXANK, and CIITA as novel
      targets of class IIa HDACs and suggest that these deacetylases play a role in
      regulating MHCII expression.

PMID- 15964853
TI  - Cyclooxygenase-2-mediated DNA damage.
AB  - Rat intestinal epithelial cells that express the cyclooxygenase-2 (COX-2) gene
      permanently (RIES cells) were used as a model of in vivo oxidative stress. A
      targeted lipidomics approach showed that 15(S)-hydroxyeicosatetraenoic acid
      (15(S)-HETE) was the major hydroxylated non-esterified lipid formed in
      unstimulated intact cells. The corresponding hydroperoxide, 15(S)
      hydroperoxyeicosatetraenoic acid (15(S)-HPETE) undergoes homolytic decomposition
      to the DNA-reactive bifunctional electrophile 4-oxo-2(E)-nonenal, a precursor of
      heptanone-etheno-2'-deoxyguanosine. This etheno adduct was identified in the DNA
      of RIES cells. A dose-dependent increase in adduct levels was observed in the
      presence of vitamin C. This suggested that vitamin C increased lipid
      hydroperoxide-mediated 4-oxo-2(E)-nonenal formation in the cells. The selective
      COX-2 inhibitor NS-398 was protective against cellular DNA damage but was less
      effective if vitamin C was present. Prostaglandin E(2) and 15(S)-HETE
      biosynthesis were completely inhibited by 110 mum NS-398 in the intact RIES
      cells. No inhibition of COX-1 was detected in the wild-type RIE cells at this
      concentration of NS-398. Arachidonic acid treatment of RIES cell lysates and
      ionophore stimulation of intact RIES cells produced significantly more 15(R)-HETE
      than the untreated intact cells. These preparations also both produced 11(R)
      HETE, which was not detected in the intact cells. Aspirin treatment of the intact
      unstimulated RIES cells resulted in the exclusive formation of 15(R)-HETE in
      amounts that were slightly higher than the original 15(S)-HETE observed in the
      absence of aspirin, implying that significant amounts of 15(R)-HPETE had also
      been formed. 15(R)-HPETE should give exactly the same amount of heptanone-etheno
      2'-deoxyguanosine as its 15(S)-enantiomer. However, no increase in heptanone
      etheno adduct formation occurred in the aspirin-treated cells. The present study
      suggests a potential mechanism of tumorigenesis that involves DNA adduct
      formation from COX-2-mediated lipid peroxidation rather than prostaglandin
      formation. Therefore, inhibition of COX-2-mediated lipid hydroperoxide formation
      offers a potential therapeutic alternative to COX-2 inhibitors in chemoprevention
      strategies.

PMID- 15964855
TI  - The use of contrast echocardiography: a matter of clinical judgement.

PMID- 15964857
TI  - Cardiovascular pre-participation screening of young competitive athletes for
      prevention of sudden death: proposal for a common European protocol.

PMID- 15964858
TI  - 'Tib the balance': the search for the optimal hormone replacement therapy.

PMID- 15964859
TI  - Risk for schizophrenia and schizophrenia-like psychosis among patients with
      epilepsy: population based cohort study.
AB  - OBJECTIVES: To investigate whether age at onset of epilepsy, type of epilepsy,
      family history of psychosis, or family history of epilepsy affect the risk of
      schizophrenia or schizophrenia-like psychosis among patients with epilepsy.
      DESIGN: Comparison of population based data. SETTING: Danish longitudinal
      registers. SUBJECTS: The cohort comprised 2.27 million people. MAIN OUTCOME
      MEASURES: Epilepsy, psychosis, personal birth data. RESULTS: We found an
      increased risk of schizophrenia (relative risk 2.48, 95% confidence interval 2.20
      to 2.80) and schizophrenia-like psychosis (2.93, 2.69 to 3.20) in people with a
      history of epilepsy. The effect of epilepsy was the same in men and in women and
      increased with age. Family history of psychosis and a family history of epilepsy
      were significant risk factors for schizophrenia and schizophrenia-like psychosis,
      and the effect of epilepsy, both in cases and families, was greater among people
      with no family history of psychosis. In addition, the increased risk for
      schizophrenia or schizophrenia-like psychosis did not differ by type of epilepsy
      but increased with increasing number of admissions to hospital and, particularly,
      was significantly greater for people first admitted for epilepsy at later ages.
      CONCLUSIONS: There is a strong association between epilepsy and schizophrenia or
      schizophrenia-like psychosis. The two conditions may share common genetic or
      environmental causes.

PMID- 15964860
TI  - Intussusception and rotavirus associated hospitalisation in New Zealand.
AB  - AIMS: To describe the epidemiology of intussusception and its relation to
      rotavirus associated hospitalisation in New Zealand. METHODS: National hospital
      discharge data between January 1998 and June 2003 for all children younger than 3
      years of age with intussusception were reviewed. Independently, children from the
      same age group, admitted to eight paediatric units with rotavirus gastroenteritis
      between May 1998 and May 2000, were identified prospectively. Epidemiological
      characteristics of cases with intussusception were compared with those of
      hospitalised rotavirus disease. RESULTS: During the 5.5 year study period, there
      were 277 cases of intussusception and no deaths. Most (72%) occurred in the first
      year of life (age adjusted incident rate 65 per 100,000 child-years, 95% CI 56 to
      74). Risk of intussusception was less in females (risk ratio 0.58; 95% CI 0.43 to
      0.78) and for Maori (risk ratio 0.52; 95% CI 0.35 to 0.77) when compared with
      European infants. In contrast to hospitalised rotavirus cases, intussusception
      peaked at a younger age and lacked seasonality. CONCLUSIONS: This study provides
      national baseline data on intussusception for future rotavirus vaccine programmes
      in New Zealand. Wild-type rotaviruses do not appear to have a major role in
      triggering intussusception. Prospective surveillance systems, using standardised
      case definitions and nested case-control methodology, are needed to further our
      understanding of the aetiology and epidemiology of intussusception.

PMID- 15964861
TI  - The burden of cholera in the slums of Kolkata, India: data from a prospective,
      community based study.
AB  - AIMS: To conduct a prospective, community based study in an impoverished urban
      site in Kolkata (formerly Calcutta) in order to measure the burden of cholera,
      describe its epidemiology, and search for potential risk factors that could be
      addressed by public health strategies. METHODS: The study population was
      enumerated at the beginning and end of the study period. Surveillance through
      five field outposts and two referral hospitals for acute, watery, non-bloody
      diarrhoea was conducted from 1 May 2003 to 30 April 2004. Data and a stool sample
      for culture of Vibrio cholerae were collected from each patient. Treatment was
      provided in accordance with national guidelines. RESULTS: From 62 329 individuals
      under surveillance, 3284 diarrhoea episodes were detected, of which 3276 (99%)
      had a stool sample collected and 126 (4%) were culture confirmed cholera.
      Nineteen (15%) were children less than 2 years of age, 29 (23%) had severe
      dehydration, and 48 (38%) were hospitalised. Risk factors for cholera included a
      household member with cholera during the period of surveillance, young age, and
      lower educational level. CONCLUSIONS: There was a substantial burden of cholera
      in Kolkata with risk factors not easily amenable to intervention. Young children
      bear the brunt not only of diarrhoeal diseases in general, but of cholera as
      well. Mass vaccination could be a potentially useful tool to prevent and control
      seasonal cholera in this community.

PMID- 15964862
TI  - Outcome of HIV infected children with culture confirmed tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) is an important disease in human immunodeficiency
      virus (HIV) infected children living in regions where TB is endemic. There are
      limited data on the outcome of culture confirmed TB in HIV infected children.
      AIMS AND METHODS: To describe the outcome on TB therapy and overall mortality in
      HIV infected children with culture confirmed TB through a retrospective cohort
      study. RESULTS: Eighty seven children, median age 24 months, contributed to 93 TB
      episodes; six children had two confirmed episodes. Pulmonary disease (PTB) was
      present in 71 episodes (76.3%), extrapulmonary disease (EPTB) in 43 (46.2%), and
      of these, both PTB and EPTB were present in 21 (22.6%). There was cure based on
      bacteriological and/or radiological criteria in 54 episodes (58.1%). Eighteen
      children died during TB therapy and there were a total of 34 deaths (39.1%). In
      univariate analysis (n = 87 patients), severe malnutrition, age < or =1 year, and
      a negative tuberculin skin test were significant risk factors for death during TB
      therapy. In multivariate survival analysis (n = 87 patients), HIV disease
      category, severe malnutrition at diagnosis, and lack of cure at the end of TB
      therapy were significantly associated with overall mortality. CONCLUSION: In the
      absence of antiretroviral therapy, HIV infected children with confirmed TB have
      poor outcomes on antituberculosis therapy and are at high risk of death during
      and after completion of antituberculosis therapy, especially due to non-TB
      related causes. There is an urgent need to optimise and monitor antituberculosis
      therapy in HIV infected children and to improve access to TB and other
      preventative therapy.

PMID- 15964863
TI  - The denominator in general practice, a new approach from the Intego database.
AB  - BACKGROUND: To determine the denominator or the 'population at risk' is a problem
      which has long been encountered in general practice-based epidemiological
      research. It is important for calculating epidemiological figures. OBJECTIVES:
      The aim of this article is to demonstrate how in the absence of a patient list, a
      reliable denominator can be calculated, starting from the number of patients who
      contacted their GP in the period of one year. Therefore a brief overview will be
      given from known approaches, then the new approach will be illustrated on a
      database named Intego, with data from 43 general practices in Belgium. METHODS:
      The Intego database contains information about patient contacts, diagnoses,
      laboratory results and drug prescriptions, extracted from the participants'
      structured electronic medical record system. The number of patients who contacted
      the practice in a year can be calculated from the Intego data. On the other hand,
      the percentage of the population that consults a GP during a particular period
      was obtained from the reimbursement claims data available from the sickness
      funds. By combining these two datasets, stratified by age, gender and district, a
      correction factor was calculated. An estimate of the real size of the Intego
      practice populations was obtained by extrapolating the yearly contact group by
      this factor. RESULTS: In 2003 according the Intego-register, 64,161 patients
      contacted their family practice and this correlated with an estimated practice
      population of 80,094 patients. The absence of the socio-economic status in the
      estimation is irrelevant in our model of estimating the practice population.
      CONCLUSION: The availability of a denominator in general practice-based research
      is essential to calculate epidemiological figures. This method using a correction
      factor makes it possible to calculate a reliable practice population. A similar
      approach will probably also be applicable in other European countries.

PMID- 15964864
TI  - Randomized trial in family practice of a brief intervention to reduce STI risk in
      young adults.

PMID- 15964865
TI  - Developing a standard short questionnaire for the assessment of patient
      satisfaction with out-of-hours primary care.
AB  - BACKGROUND: Governmental reviews of out-of-hours services in England and Scotland
      have recommended that a standard questionnaire should be used to assess patient
      satisfaction. This is important because of the rapid introduction of new forms of
      care. OBJECTIVE: To produce a brief, reliable and valid measure of patient
      satisfaction for use by a wide variety of providers of out-of-hours primary care.
      METHODS: The Short Questionnaire for Out-of-Hours care was designed and compared
      with a longer questionnaire which had been validated and used in earlier
      research. Questionnaires were sent to 1906 people contacting an out-of-hours GP
      co-operative. Three versions of the short questionnaire were used with different
      formats. Analysis compared the response rates, measurement properties, concurrent
      and construct validity of the short and long questionnaires, and of different
      versions of the short questionnaire. RESULTS AND CONCLUSIONS: There was no
      significant difference in the overall response rates obtained from the short or
      long questionnaires (45.7% versus 41.9%; P = 0.17). The effective response rate
      of questionnaires from which all satisfaction scales could be calculated was
      higher for the short questionnaire (43.0% versus 36.4%; P = 0.01). There were no
      significant differences in response rates or distribution of responses between
      different versions of the short questionnaire. There was moderate agreement
      between items on the short questionnaire and corresponding scales on the long
      questionnaire. Scores using the short questionnaire showed anticipated
      relationships with the age and sex of patients and with characteristics of how
      the service was delivered. The SQOC is valid and reliable for routine service
      use.

PMID- 15964866
TI  - Prevalence of undetected persistent airflow obstruction in male smokers 40-65
      years old.
AB  - BACKGROUND: Airflow obstruction in smokers is often diagnosed relatively late.
      Earlier detection of airflow obstruction and smoking cessation may result in
      significant health gain. OBJECTIVE: To determine the prevalence of previously
      undetected persistent airflow obstruction according to WHO/GOLD criteria in male
      smokers aged 40 to 65 years and its correlation with age, smoking history and the
      presence of coughing. METHODS: In a cross-sectional study among 805 male smokers
      aged 40-65 years spirometry was performed according to ATS recommendations. In
      participants with low lung function (FEV1 < 85% predicted) a bronchodilator test
      was performed. RESULTS: In 702 participants [mean age 50 years (SD 6.6), mean
      number of pack years 24.7 (SD 9.6)] with acceptable spirometric curves,
      previously undetected airflow obstruction was found in 210 subjects (29.9%; 95%
      CI 26.5-33.4): mild airflow obstruction (GOLD stage 1) in 182 subjects (25.9%;
      22.7-29.3) and moderate airflow obstruction (GOLD stage 2) in 28 (4.0%; 2.7-5.7).
      In the older age group (>55 years) airflow obstruction (GOLD 1 or higher) was
      found in 45% versus 21% in the youngest age group (40-44 years). In subjects with
      > or =30 pack years the prevalence of airflow obstruction was 45% versus 20%
      among those with <20 pack years. In smokers reporting coughing the prevalence was
      47% versus 25% in those not reporting this symptom. CONCLUSION: The prevalence of
      undetected persistent airflow obstruction in middle-aged smokers is high.
      Targeted screening therefore, especially in smokers aged 40-65 years needs to be
      considered.

PMID- 15964867
TI  - Diagnostic yield of patient-activated loop recorders for detecting heart rhythm
      abnormalities in general practice: a randomised clinical trial.
AB  - BACKGROUND: Because palpitations and light headedness often occur paroxysmally
      these complaints are difficult to diagnose. The hazards for a GP are too many
      diagnostic interventions for worried well and too few diagnostics for potentially
      life threatening complaints. OBJECTIVES: Patient-activated memo event recorders
      have proved to be successful in diagnosing episodes of cardiac arrythmias in
      secondary care. We tested the diagnostic yield of these devices in general
      practice. METHODS: A randomized clinical trial in general practice. Consecutive
      patients with complaints of palpitations or light-headedness were randomized to
      either usual care or usual care plus event-recorder. The main outcome was the
      difference in explained episodes. Secondary outcomes were the differences in the
      number and character of cardiac diagnoses and the feasibility of the event
      recorder. RESULTS: There were fewer patients without a diagnosis in the
      intervention group (17% vs 38%; RR = 0.5, 95% CI 0.3 to 0.7) and more patients
      with a cardiac diagnosis (67% vs. 27%: RR 2.5, CI 1.8 to 3,5). More relevant
      cardiac arrhythmias were detected (22% vs 7%) with event recording than with
      usual care (RR 3.2, 95% CI 1.5 to 6.8). CONCLUSION: Patient-activated loop
      recorders are feasible and effective diagnostic tools in patients with
      palpitations or light-headedness in primary care. More research into patient
      characteristics and selection criteria is needed to fine-tune the use of these
      devices in primary care.

PMID- 15964868
TI  - Establishing a welfare advice service in family practices: views of advice
      workers and primary care staff.
AB  - BACKGROUND: The placement of welfare advice services in family practice to assist
      patients with health-related social and economic issues (e.g. disability
      benefits) has gathered momentum over the last decade in the UK. This expansion of
      primary care raises a number of issues for practices hosting these services.
      OBJECTIVES: To gain the views of advice workers and primary care staff about the
      issues raised in hosting a welfare advice service across 30 practices in inner
      city Bradford. METHODS: Views were obtained through focus groups with six advice
      workers, and primary care staff in 14 practices. A questionnaire was also posted
      to all practice managers asking their opinions about the service. RESULTS: The
      focus groups highlighted a number of advantages for patients, including
      improvements in health and quality of life through increased income and reduced
      stress from social and economic issues. For practice staff, the service provided
      a resource to refer patients for welfare advice, reducing the time spent dealing
      with welfare issues, thereby reducing workload. This was confirmed in the
      questionnaire to practice managers where 72% said the service had saved time for
      GPs and reception/office staff. The advice workers raised concerns about the
      perceived level of commitment to the service from some staff at some practices.
      Practice staff were particularly concerned about the need for feedback about
      referrals. CONCLUSION: Providing welfare advice in family practice can act as a
      valuable resource for primary care staff helping to address their patients health
      related social and economic needs.

PMID- 15964869
TI  - Reassurance or judgement? Parents' views on the delivery of child health
      surveillance programmes.
AB  - BACKGROUND: The first year of a child's life is a crucial time for child
      development. Current guidance about child health surveillance and health
      promotion programmes emphasises a partnership approach between health
      professionals and parents when it comes to child health care. Parents' voices
      have been largely absent from discussions about local child health programmes.
      For partnership working to be effective and for local services to be able to
      evolve effectively parents' views are vital. OBJECTIVES: This study aimed to
      explore parents' views on the child health surveillance and health promotion
      programmes offered during the first year of their child's life. The study aimed
      to be consumer-led through the involvement of lead parents in all stages of the
      research process. METHODS: This study employed a qualitative methodology of focus
      groups and individual interviews. 35 participants were drawn from three general
      practices using a snowball sampling technique. Eligibility was determined as
      parents with a child under the age of one year or expecting a baby within the
      study timescale and registered at one of the 3 general practices. Focus groups
      were led by three 'parent-researchers' and individual interviews were conducted
      by a researcher. All focus groups and interviews were tape-recorded, transcribed
      and analysed using Atlas.Ti. RESULTS: Several main themes were identified in this
      study. Firstly, when discussing scheduled health checks for children under one
      year of age parents expressed more positive feelings for the eight-week check
      which was seen to be comprehensive and informative rather than the eight-month
      check which was viewed as bureaucratic and less reassuring. Secondly, parents
      clearly articulated a need for reassurance and support from health professionals
      involved in child health surveillance and health promotion programmes. Thirdly, a
      crucial professional in the delivery of these programmes was the health visitor.
      Whilst parents expressed support for the concept of health visitors some health
      visitors were seen as bureaucratic and as making judgements of need based on
      socio-economic factors. Finally, some parents spoke of feeling excluded from
      accessing support as they were deemed not to be 'in need'. CONCLUSIONS: Wider
      concepts of partnership working between health professionals and parents, and,
      needs assessment are important to this study. Crucial elements of the partnership
      appear to be missing and this coupled with needs assessments that leave parents
      feeling excluded mean that there are discrepancies between expectations and
      experiences of parents. These issues require consideration in order to improve
      services and experiences.

PMID- 15964870
TI  - Consultation for and identification of child and adolescent psychological
      problems in Dutch general practice.
AB  - BACKGROUND: Child and adolescent psychological problems are rarely brought to the
      attention of GPs. Children and adolescents with psychological problems who do
      visit their GP are seldom identified as such by GPs. OBJECTIVE: To investigate in
      a general population sample of 2,449 Dutch children and adolescents (4-17 years)
      GP consultation and GP diagnoses of child psychological problems, and the
      influence of child and family characteristics upon these variables. METHODS: The
      degree to which parent, teacher, and adolescent reports of the presence of child
      psychological problems are in concordance with GP diagnoses of these problems was
      determined. Logistic regression analyses were used to examine correlates of GP
      consultation and psychological diagnoses. RESULTS: Approximately 80% of children
      and adolescents with psychological problems had visited their GP within the
      preceding year. GP consultation was most strongly associated with
      child/adolescent chronic physical disorders. Concordance between GP psychological
      diagnoses and parent, teacher, and adolescent reports of psychological problems
      was limited. Children and adolescents with psychological problems according to
      parent or teacher report, children with school problems, young boys, adolescents
      with negative health perceptions, and adolescents from single parent families
      were more likely to be diagnosed with psychological problems by GPs. CONCLUSION:
      Improving GPs' interview techniques, introducing standardised screening measures
      in general practice, increasing GPs' awareness of the possible presence of
      psychological problems in children consulting for physical problems, and
      strengthening collaboration between GPs and mental health professionals may
      increase GP identification of child psychological problems and enhance access to
      care for those in need.

PMID- 15964871
TI  - Early symptoms of ovarian cancer: a case-control study without recall bias.
AB  - BACKGROUND: Ovarian cancer is usually diagnosed after it has spread and is
      difficult to cure. Previous attempts to identify early symptoms have either
      lacked a control group or have been based on interviews of cases, with possible
      recall bias. OBJECTIVE: The purpose of this study was to identify early symptoms
      of ovarian cancer by reviewing prediagnostic medical records, free of recall
      bias, and comparing women with and without ovarian cancer. METHODS: In an
      integrated health care delivery system, symptoms recorded in medical records of
      102 women with ovarian cancer during the two years before diagnosis were compared
      with those of 102 matched control women. RESULTS: More cases than controls
      complained of several symptoms up to one year before diagnosis. Most of these
      symptoms were abdominal or gastrointestinal in nature and were more prevalent in
      the advanced stage cases. Other symptom sites included pelvic, urinary, back, and
      systemic. Because case-control differences were not large and prevalence is low,
      positive predictive values were generally quite low. CONCLUSION: Previous reports
      of early symptoms of ovarian cancer were confirmed in a study with a control
      group and free of recall bias. It is not clear that these symptoms occurred while
      the disease was still localized. Because hundreds of women would have to be
      investigated to detect one case of ovarian cancer, the clinical utility of these
      symptoms is uncertain. Nevertheless, health care providers should keep ovarian
      cancer in mind, when women present with symptoms such as abdominal pain and
      bloating.

PMID- 15964872
TI  - Which anthropometric measurements is most closely related to elevated blood
      pressure?
AB  - BACKGROUND: Epidemiological studies find a progressive increase in the prevalence
      of elevated blood pressure with increasing adipose tissue. But there is no common
      opinion about which effectiveness of the anthropometric measurement tools
      indicating general or android obesity are most important to follow up in patients
      with elevated blood pressures. OBJECTIVES: To identify which anthropometric
      measurements are most closely related to blood pressure elevation. METHODS: A
      cross-sectional descriptive study of 1727 subjects [894 (50.6%) men and 833
      (48.2%) women, aged 18-65 years old] was held in Edirne, Turkey. Each subject's
      weight, height, waist and hip circumference, triceps skin fold and blood
      pressures was measured; waist to hip ratio and body mass index were calculated.
      The relations between blood pressure and different anthropometric variables in
      both genders were investigated in linear regression models. RESULTS: The mean
      systolic and diastolic blood pressures were 123.49 +/- 17.60 and 78.79 +/- 10.37
      mmHg. According to body mass index 23.7% of the subjects were obese (.29.9
      kg/m(2)). When waist circumference cut-off points were compared with waist to hip
      ratio the android obesity ratio was doubled (32.3% versus 16.6%). 119 subjects
      (6.8%) were not obese according to body mass index but nonetheless had waist
      circumference measurements above the cut-off points suggesting a high
      cardiovascular risk. In the linear regression models waist circumference was
      found to be an independent risk factor for blood pressure in men; however body
      mass was more important index and waist circumference somewhat less so for women.
      CONCLUSION: In primary care waist circumference should be a useful tool screening
      for and following android obesity in patients with elevated blood pressure.

PMID- 15964873
TI  - Nurse practitioner and practice nurses' use of research information in clinical
      decision making: findings from an exploratory study.
AB  - BACKGROUND: There is a lack of evidence regarding the kinds of decisions made by
      primary care nurses and the information sources they use in clinical decision
      making. OBJECTIVE: To describe the decisions made by nurses working in general
      practice and the sources of information they use to underpin those decisions.
      METHODS: Qualitative methods (interviews, observation, documentary analysis) were
      used to collect data on the clinical decision making and information seeking
      behaviour of a purposive sample of 29 practice nurses and four nurse
      practitioners from general practices in the North of England. Data were collected
      November 2001-September 2002. RESULTS: A seven-fold typology captured the types
      of decisions the nurses made on a daily basis concerning assessment, diagnosis,
      intervention, referral, communication, service delivery and organization (SDO)
      and information seeking. Faced with clinical uncertainty, the majority of the
      nurses in the study relied on personal experience, or obtained advice and
      information from GP or other colleagues. These 'human sources' of information
      were overwhelmingly preferred to text or on-line resources. Despite encounters
      with evidence-based resources through continuing professional development, the
      nurses rarely used them to seek answers to routine clinical questions.
      CONCLUSION: The decisions of the nurses in the study were mainly concerned with
      undifferentiated diagnosis and treatment, in the context of acute conditions and
      chronic disease management. 'Human sources' of information were preferred to any
      other; however, we do not know whether information obtained from colleagues is
      based on research.

PMID- 15964874
TI  - The role for vitamin B-6 as treatment for depression: a systematic review.
AB  - BACKGROUND: Major depression is the leading cause of disability worldwide, and
      among the 10 most frequent indications for using alternative medicine therapies,
      especially dietary supplements. OBJECTIVE: To assess the evidence evaluating
      vitamin B-6 supplementation as treatment for depression. METHODS: Medline,
      Psychinfo, AMED, and Cochrane Controlled Trials Register were searched from
      database inception through September 2001. All randomized controlled trials,
      controlled clinical trials, intervention studies, case-control studies, reviews,
      and case reports examining the evidence behind vitamin B-6 in depression among
      humans were selected. No limits were placed for demographics or co-morbidities.
      Only English language papers were abstracted and assessed for trial quality. Two
      abstractors independently evaluated each study, then reconciled findings. As data
      were available, between group treatment effect size was noted or, as needed,
      calculated. When studies reported outcome effects using multiple measures, data
      were abstracted to permit the greatest possible comparisons among papers.
      RESULTS: Ten articles met inclusion criteria; three reviews, one case report,
      five RCTs, and one intervention study. There was no common outcome measure among
      all studies, eliminating opportunity for direct comparison of effect sizes. As an
      alternate means of comparison, effects were plotted as they related to the null
      hypothesis. CONCLUSION: Viewed as a whole, meaningful treatment effect of vitamin
      B-6 for depression in general was not apparent. However, examination of papers
      addressing depression in pre-menopausal women only, reveals a consistent message
      about the value of using vitamin B-6 supplementation. Further study of vitamin B
      6 as independent and adjuvant therapy for hormone related depression in women is
      indicated.

PMID- 15964875
TI  - Results of computed tomography in family practitioners' patients with non-acute
      abdominal pain.
AB  - OBJECTIVES: The utility of abdominal computerized tomography (CT) for evaluating
      abdominal pain in non-emergency, primary care outpatients is unknown. Family
      practice patients commonly report abdominal pain. METHODS: We reviewed the
      records of health maintenance organization primary care outpatients <2 years
      after they had undergone CT for abdominal pain and assessed demographic
      variables, clinical and laboratory data, CT findings and final diagnoses.
      RESULTS: We studied 137 patients: age 58.1 +/- 16.1 years (mean +/- SD), 80
      (58.4%) females. Fifty (36.5%) patients had > or =1 warning clinical or
      laboratory feature. Positive (etiologic) and negative CT reports and unrelated
      and multiple CT findings occurred in 16 (11.7%), 104 (75.9%), 16 (11.7%) and 1
      (0.7%) patients, respectively. Positive findings occurred in 16 (32.0%) patients
      with > or =1 warning feature and 1 (1.2%) patient (including the 1 patient with
      multiple findings) with no warning feature (P < 0.0001). One (6.3%) unrelated
      finding led to treatment, ovariectomy for a benign tumor. Fifty-four (39.4%)
      patients had a final diagnosis. CONCLUSIONS: A majority of outpatients who had CT
      for abdominal pain received no diagnosis, and CT was rarely diagnostic for
      patients lacking a warning feature. Positive and unrelated CT findings were
      equally prevalent, and the latter were not beneficial.

PMID- 15964876
TI  - A case study: surface contamination of cyclophosphamide due to working practices
      and cleaning procedures in two Italian hospitals.
AB  - The efficacy of preventive and organisational measures implemented in Italy to
      prevent the contamination of cytotoxic drug preparation rooms has been
      investigated, and oncologic wards of two Italian hospitals were examined. The
      sampling strategy was based not only on potential sources of contamination but
      also on responses to detailed questionnaires on workplace practices and work
      organisation. Wipe samples were taken from different surfaces of preparation
      rooms, before and after the work shift, over a span of a month. Cyclophosphamide
      was taken as the marker drug that reflects exposure to cytotoxic drugs, being
      measurable by GC/MS. In one of the two hospitals (Hospital A), a large amount of
      cyclophosphamide was found, both before and after shift, on the workbench (median
      value, 2.55 microg dm(-2), before shift), on the floor between the operator
      working position and the waste bin (>10 microg dm(-2), after shift), as also on
      door handles and storage shelves. No quantifiable levels of cytotoxic drug were
      detected in the second hospital investigated (Hospital B). These results could be
      attributed to the efficacy of cleaning procedures and working practices. In fact,
      both hospitals were provided with vertical-laminar airflow hoods and the (male)
      nurses had attended special training courses; but in Hospital A, cleaning
      procedures were carried out without substances used specifically for the cleaning
      of surfaces contaminated by cytotoxic drugs such as sodium hypochlorite. Working
      practices did not include Luer Lock devices. Cyclophosphamide concentrations
      found in both hospitals, compared with the quantities of drug handled, gave
      evidence of the importance of the correct handling of cytotoxic agents as a major
      tool in reducing contamination levels. The results reveal the insufficiency of
      the risk management measures which do not take into account working practices
      that are prevailing, and stress the necessity for periodic environmental
      monitoring, indispensable for evolving effective procedures to prevent
      antineoplastic drug exposure.

PMID- 15964877
TI  - Should styrene be sampled on the left or right shoulder?--An important question
      in employee self-assessment.
AB  - A self-operated personal sampling technique called 'self assessment of exposure'
      (SAE) has been suggested as an easy method for collecting inhalation exposure
      data, as the workers themselves are performing the sampling. Employers and
      employees have raised the question of whether a different estimate of the air
      concentration is likely to be obtained depending on whether the sampler is
      fastened at the left or the right shoulder. In order to answer this question, the
      exposure to styrene vapour in two different small enterprises within the
      reinforced plastics industry was measured. Seven workers participated and the air
      sampling was performed by diffusive sampling. We observed no statistically
      significant difference in the determined air concentration of styrene between the
      left and right shoulder (P = 0.878). The results strongly indicate that the
      fastening of a sampler on the left or right shoulder does not produce a
      difference in the estimation of the inhalation exposure. SAE can thus be used to
      collect reliable exposure data of styrene vapour. The reliability of SAE will
      most certainly inspire occupational hygienists, physicians and other experts to
      involve the workers in repeated exposure measurements. Taking the exposure
      variability into account, repeated measurements are crucial when evaluating acute
      and chronic health effects following inhalation exposure to gases and vapours
      from chemical hazards.

PMID- 15964878
TI  - Exposure to antineoplastic drugs in two UK hospital pharmacy units.
AB  - STUDY OBJECTIVES: To carry out an environmental and biological monitoring study
      in two UK hospital pharmacy units involved in the preparation of antineoplastic
      drugs. PARTICIPANTS AND METHODS: The two units studied used isolators for drug
      preparation. One used isolators operating at positive pressure relative to
      external atmospheric pressure, whereas the other used negative pressure
      isolators. Monitoring utilized the measurements of methotrexate, ifosfamide,
      cyclophosphamide and platinum reflecting the platino-coordinated drugs, such as
      cisplatin and carboplatin. Personal and static atmospheric and floor wipe samples
      were collected together with preshift and post-shift urine samples over a 4-day
      consecutive monitoring period. During the study period both units operated to
      their normal procedures. RESULTS: Measurable amounts of cytotoxic drugs were
      detected on the floors of both units and on the disposable gloves worn by staff
      preparing the drugs. There was also evidence in both units of some very low-level
      drug absorption from urine measurements, using the most sensitive analytical
      technique of platinum analysis. The absorption of platinum containing drugs in
      the unit using negative-pressure isolators was significantly higher, even though
      less platinum containing drug was prepared per day. Urine measurements in both
      units were below the detection limit for the other measured drugs. Although the
      unit using positive-pressure isolators handled daily approximately five times the
      drug quantities handled with the negative pressure unit, the general levels of
      external contamination and urine measurements did not reflect this difference.
      Comparison of the relative levels of glove and floor contamination between the
      two units was not clear-cut and appeared to depend on the specific cytotoxic drug
      being monitored. CONCLUSIONS: The levels of external contamination on the floor
      and gloves, and absorbed dose from urine measurements found in this study showed
      considerable improvement over many earlier, non-UK studies using comparable
      exposure measurements. These earlier studies were in facilities using laminar
      flow/microbiological safety cabinets and where staff were likely to be involved
      in both drug preparation and administration. Our data did not suggest that the
      differential pressure of the isolator to the pharmacy atmosphere was an
      overarching factor in the risk of operator exposure under normal operation. There
      remains a need to investigate the sources of the low-level drug contamination
      found in the pharmacies even when using isolators to prepare cytotoxic drugs.
      This study, and related studies of hospital oncology ward staff, appear to be the
      only recent UK studies of occupational cytotoxic drug exposure using
      environmental and biological monitoring techniques.

PMID- 15964879
TI  - Long-term effects of elemental mercury on renal function in miners of the Idrija
      Mercury Mine.
AB  - BACKGROUND: The kidneys are one of the main target organs for elemental mercury
      (Hg(0)). The influence of Hg(0) on kidneys has been extensively studied but the
      long-term effects on this organ have not yet been determined with certainty. The
      basic aim of this research was to study the effects of a long-term exposure to
      Hg(0) vapours on the renal function in miners in the post-exposure period.
      METHODS: The population studied comprised 53 miners (33 active and 20 retired)
      from the Idrija Mercury Mine as the exposed miners group and 53 unexposed workers
      as the control group. On the basis of mine exposure records (air and biological
      monitoring), the environmental and biological indicators of the past exposure to
      Hg(0) were calculated for each miner. Kidney function was determined in both
      groups, i.e. in the exposed miners as well as in the controls. Glomerular kidney
      function was evaluated by a quantitative analysis of albumin and IgG in urine.
      Tubular kidney function, however, was determined by a quantitative analysis of
      alpha(1)-microglobulin in urine and by the enzymatic activity of N-acetyl-beta-d
      glucosaminidase (NAG). RESULTS: The mean exposure time in miners was 15 years.
      The total number of cycles of exposure ranged from 13 to 119. The mean annual
      time-weighted exposure was 0.29 mg m(-3) and the mean integrated exposure
      intensity (IEI) was 1413 mg m(-3)-h. Throughout the period of exposure the
      average urine mercury concentration in miners was 68.24 microg l(-1) and the
      average sum of peak urine mercury concentrations was 3901 microg l(-1). Albumin,
      IgG and alpha(1)-microglobulin in urine were significantly elevated in the
      exposed miners compared with the unexposed controls (t = 2.17, P = 0.03; t =
      2.81, P < 0.01; and t = 2.07, P = 0.04). No significant differences were found in
      the urine NAG activity when the exposed miners and the unexposed workers were
      compared. Among the indicators of renal function only alpha(1)-microglobulin in
      the urine correlated significantly with the IEI (r = 0.73; P <or= 0.01) and with
      the sum of peak mercury urine concentrations (r = 0.67; P <or= 0.01) in the group
      of miners who still worked, while no significant correlations were found between
      these parameters in the group of the retired miners. CONCLUSION: The results of
      the differences in albumin, IgG and alpha(1)-microglobulin concentrations in
      urine between the exposed miners and unexposed controls suggest that a long-term
      occupational exposure to Hg(0) could cause renal dysfunction. A high correlation
      between alpha(1)-microglobulin in urine and the IEI as well as between alpha(1)
      microglobulin in urine and the sum of peak urine mercury concentrations in the
      group of active but no longer exposed miners indicates that a long-term
      occupational exposure to Hg(0) may cause a non-permanent tubular dysfunction.

PMID- 15964880
TI  - Diesel particulates--recent progress on an old issue.

PMID- 15964881
TI  - Exposure-related health effects of silver and silver compounds: a review.
AB  - A critical review of studies examining exposures to the various forms of silver
      was conducted to determine if some silver species are more toxic than others. The
      impetus behind conducting this review is that several occupational exposure
      limits and guidelines exist for silver, but the values for each depend on the
      form of silver as well as the individual agency making the recommendations. For
      instance, the American Conference of Governmental Industrial Hygienists has
      established separate threshold limit values for metallic silver (0.1 mg/m3) and
      soluble compounds of silver (0.01 mg/m3). On the other hand, the permissible
      exposure limit (PEL) recommended by the Occupational Safety and Health
      Administration and the Mine Safety and Health Administration and the recommended
      exposure limit set by the National Institute for Occupational Safety and Health
      is 0.01 mg/m3 for all forms of silver. The adverse effects of chronic exposure to
      silver are a permanent bluish-gray discoloration of the skin (argyria) or eyes
      (argyrosis). Most studies discuss cases of argyria and argyrosis that have
      resulted primarily from exposure to the soluble forms of silver. Besides argyria
      and argyrosis, exposure to soluble silver compounds may produce other toxic
      effects, including liver and kidney damage, irritation of the eyes, skin,
      respiratory, and intestinal tract, and changes in blood cells. Metallic silver
      appears to pose minimal risk to health. The current occupational exposure limits
      do not reflect the apparent difference in toxicities between soluble and metallic
      silver; thus, many researchers have recommended that separate PELs be
      established.

PMID- 15964882
TI  - An analysis of the development of Canadian food fortification policies: the case
      of vitamin B.
AB  - The concept of fortification, or the deliberate addition of synthetic vitamins to
      food, arose for the first time in Canada during the 1930s. The availability of
      new technology introduced a debate over the merits of food fortification as a
      tool to improve the nutritional health of the population. Through the use of two
      case studies, vitamin B(1) (thiamin) in the 1930s and vitamin B(9) (folic acid)
      in the 1990s, this paper examines the development of Canadian policies on food
      fortification. It presents early ideas about the use of food fortification to
      improve the health of the population, discusses shifts in attitudes toward
      fortification, and examines the intersections between scientific knowledge, trade
      considerations, and public health concerns.

PMID- 15964883
TI  - Effective mine risk education in war-zone areas--a shared responsibility.
AB  - The focus of this paper is effective health education and promotion in the field
      of mine awareness, or what has more recently been re-titled 'mine risk
      education'. According to the United Nations, mine risk education comprises
      educational activities that aim to reduce the risk of injury from
      landmine/unexploded ordnance (UXO) through raising awareness and promoting
      behavioural change and includes public information dissemination, education and
      training, and community mine action liaison. Specifically, this paper is an
      empirical study of mine risk education practices using data collected during the
      implementation of a mine risk education programme that commenced in Lao PDR in
      1996 and is ongoing. In particular, it considers lessons learned from the
      programme's monitoring and evaluation process. The authors argue that in a
      country such as Lao PDR, where communities have lived with UXO infestation for
      over 25 years, more mine risk education is not necessarily needed. This paper
      concludes that common programmes of mine risk education using top-down
      educational methods, based on the assumption that ignorance of landmine/UXO risk
      is the key factor in mine accidents, are inadequate. Evidence from the literature
      on health promotion and the experience of the programme indicate that there is a
      need to supplement or replace existing common mine risk education practices with
      techniques that incorporate an understanding of the economic, social and
      political circumstances faced by communities at risk.

PMID- 15964884
TI  - Sexual health promotion in Chennai, India: key role of communication among social
      networks.
AB  - Communication about sex and sexual health is an important facilitator in gaining
      accurate knowledge about prevention of sexually transmitted diseases (STDs) and
      promotion of sexual health. Understanding how and with whom communication about
      sex occurs and the nature of the information exchanged is valuable in designing
      sexual risk prevention interventions. In this study of low-income communities
      residents in Chennai, India, our aim was to understand the composition of
      personal communication networks, the nature of information related to sex and
      sexual health that is exchanged in these networks and the value of communication
      among members of these networks. We conducted in-depth open-ended interviews
      using a structured interview guide with 43 individuals. We also conducted 12
      focus group discussions. Individuals were selected using snowball sampling. Our
      results indicate that information about sex and sexual health is exchanged within
      and between four groups: married women, married men, unmarried men and unmarried
      women. Communication leads to an expansion of sexual networks among unmarried men
      and treatment seeking behaviour for STDs in all groups. Unmarried men offer
      immense potential for intervention given the range of topics related to sex and
      sexual health that are discussed and the risky sexual behaviours practiced.
      Spousal communication about sexual behaviour or sexual health is minimal and
      shifting norms for prevention would be difficult. Interventions identifying
      communication networks and influencing the natural communication patterns in
      these networks may be a viable HIV prevention strategy in the study area.

PMID- 15964885
TI  - Boundary workers and the management of frustration: a case study of two Healthy
      City partnerships.
AB  - Partnerships between local governments, health districts and non-governmental and
      community-based organiza-tions are an increasingly important part of health
      promotion practice, as well as other policy and programme areas. Two inherent
      tensions in partnership working have been widely described. First, partnerships
      are generally set up as 'top down' initiatives, which advocate a 'bottom up'
      approach, with the inevitable power imbalances that this implies. Secondly, the
      gains made by partnerships tend to be limited compared with the claims made for
      them. Despite these tensions, individuals and organizations continue to devote
      considerable effort to making partnerships 'work'. This paper describes a study,
      which explored the implications of these apparent contradictions of power
      imbalance and potential disillusionment within partnerships. The study explored
      partnership working between community and statutory organizations within two very
      different Healthy Cities initiatives, one in the UK and the other in South
      Africa. This paper focuses on why the partners contributed continued effort and
      energy into maintaining the partnerships, despite their awareness of the
      constraints. Findings suggest that partners dealt with the tensions first by
      assuming a discrete identity as an 'entity of boundary people' that operates at
      the interface between the statutory sector authorities and the communities in
      question; and secondly, by reducing their activities to specific 'boundary'
      issues that do not threaten the main agenda of the authorities.

PMID- 15964886
TI  - The Singaporean response to the SARS outbreak: knowledge sufficiency versus
      public trust.
AB  - During the outbreak of severe acute respiratory syndrome (SARS) in Singapore from
      1 March to 11 May 2003, various national prevention and control measures were
      undertaken to control and eliminate the transmission of the infection. During the
      initial period of the epidemic, public communication was effected through press
      releases and media coverage of the epidemic. About a month into the epidemic, a
      public education campaign was mounted to educate Singaporeans on SARS and
      adoption of appropriate behaviours to prevent the spread of the disease. A survey
      was conducted in late April 2003 to assess Singaporeans' knowledge about SARS and
      infection control measures, and their concerns and anxiety in relation to the
      outbreak. The survey also sought to assess their confidence in the ability of
      various institutions to deal with SARS and their opinion on the seemingly tough
      measures enforced. The study involved 853 adults selected from a telephone
      sampling frame. Stratified sampling was used to ensure adequate representation
      from major ethnic groups and age groups. The study showed that the overall
      knowledge about SARS and control measures undertaken was low (mean per cent score
      of 24.5 +/- 8.9%). While 82% of respondents expressed confidence in measures
      undertaken by Tan Tock Seng Hospital (the hospital designated to manage SARS),
      only 36% had confidence in nursing homes. However, >80% of the public agreed that
      the preventive and control measures instituted were appropriate. Despite the low
      knowledge score, the overall mean satisfaction score of the government's response
      to SARS was 4.47 (out of possible highest score of 5.00), with >93% of adult
      Singaporeans indicating that they were satisfied or very satisfied with the
      government's response to SARS. Generally, Singaporeans had a high level of public
      trust (satisfaction with government, confidence in institutions, deeming
      government measures appropriate), scoring 11.4 out of possible maximum of 14. The
      disparity between low knowledge on the one hand and high confidence and trust in
      the actions of the government on the other suggests that Singaporeans do not
      require high knowledge sufficiency to be confident in measures undertaken by the
      government to control the SARS crisis.

PMID- 15964887
TI  - Implementation of a Health Impact Assessment (HIA) tool in a regional health
      organization in Sweden--a feasibility study.
AB  - During the last decade, Health Impact Assessment (HIA) has been discussed
      worldwide as being an important tool for the development of healthy public
      policy. In Sweden, the Swedish Federation of County Councils and the Swedish
      Association of Local Authorities have taken the initiative to and are responsible
      for the development of an HIA tool concerning proposed policy decisions at local
      and regional levels. The HIA tool was developed as three different templates to
      be adapted to local conditions and needs: the Health Question, the Health Matrix
      and the Health Impact Analysis. In this paper we present a feasibility study of
      the experiences of implementing this HIA tool at regional level in a Health Care
      District (SWHCD) of Stockholm County Council, based on an inductive approach and
      on principles of data triangulation. The main findings include the need for
      continuous revision of the HIA templates during the pilot period. The following
      factors were instrumental in successfully using the HIA tool in local policy
      making and management: political consensus, agreement between politicians and
      public officials on political intentions, a clear- cut decision from management,
      and offering an opportunity for training. Respondents felt that all public
      officials should use the HIA as part of their normal work routines. In
      conclusion, the HIA tool has to be locally adapted and the implementation process
      has to include close collaboration between politicians and public officials and
      be followed by continuing education, providing possibilities for a dialogue
      around the HIA tool, in order to ensure the quality of the instrument.
      Implications of the study are that the process of developing the tool has worked
      well but that the possible impacts of its use in this case remain an open
      question. However, this was not the focus of our study.

PMID- 15964888
TI  - The development of quality criteria for research: a Finnish approach.
AB  - Health promotion research is distinct in some respects from research within its
      contributing disciplines. A study was conducted in Finland to identify the
      special characteristics and distinctiveness of health promotion research, to
      develop a set of specific quality evaluation criteria for health promotion
      research, and to test the usefulness of such criteria in selecting research
      applications for funding. A wide range of discussions supplemented a systematic
      literature review with experts within and outside Finland. The review was
      conducted with regard to the content of health promotion, its basic principles,
      as well as theories and models used to steer practical health promotion
      activities. This resulted in a proposal for quality criteria for health promotion
      research. Key informants from Finnish universities and institutes evaluated the
      criteria in three Delphi rounds, and they were suitably revised. The utility of
      the revised criteria was tested using 31 research proposals. After further
      revision, the criteria were tested with a further 16 research proposals. Seven
      health promotion research quality criteria were developed by these methods, as
      were seven general criteria of research quality, applicable to all social
      research, whether in the health promotion arena or not. The 14 criteria will
      undergo continuous revision for improvement, but they are already at this stage
      thought to be suitable for use by (a) funding agencies in the design of calls for
      health promotion research proposals, and calls for tenders; (b) researchers who
      respond to calls for health promotion research proposals and/or calls for
      tenders; (c) evaluators and proposal review groups; and (d) reviewers and
      auditors of research progress.

PMID- 15964889
TI  - Teaching antiarrhythmic therapy and ECG in simulator-based interdisciplinary
      undergraduate medical education.
AB  - BACKGROUND: Third-year students in the Dresden Medical School Programme undergo a
      6 week course 'Basics of Drug Therapy' in a problem-based learning curriculum. As
      part of this course a practical seminar about antiarrhythmic drugs and ECG was
      set up. This study was conducted to evaluate the use of a simulator in this
      course. METHODS: A total of 234 students were randomly allocated to receive
      instructions with (Group S) or without (Group C [control]) the use of a
      simulator. After a lecture on antiarrhythmic drugs, arrhythmias were presented to
      Group S using an advanced life support (ALS) manikin. The students were asked to
      administer a drug or to defibrillate, and the outcome was shown on the monitor.
      The students in Group C were presented with ECG charts without a simulator. The
      course was evaluated by a questionnaire and multiple-choice questions (MCQ) about
      arrhythmias. RESULTS: We received 222 questionnaires. The content-time ratio was
      rated almost perfect in both groups, but the students in Group S rated the course
      better suited to link theory and practice. Students in Group S considered the
      simulator helpful and a good tool for teaching, and the extra effort to be
      worthwhile. A significantly higher number of students in Group S preferred
      electric cardioversion as therapy for ventricular tachycardia. CONCLUSIONS: An
      ALS manikin can be an effective tool in teaching clinical pharmacology.

PMID- 15964890
TI  - Anaesthetic management of a neonate with congenital cyst adenoid malformation.
AB  - We report the anaesthetic management of a male neonate with congenital cyst
      adenoid malformation (CCAM) of the lung who underwent thoracotomy for resection
      of CCAM 24 h after birth and again at 24 days. The initial operation involved a
      10-day admission to a paediatric intensive care unit (PICU) requiring
      ventilation, and was complicated by a pneumothorax. This report concentrates on
      the anaesthetic management for the second thoracotomy. The combination of intra
      operative remifentanil infusion and the use of ultrasound to confirm correct
      placement of epidural catheter allowed on-table tracheal extubation and a shorter
      stay in PICU. The use of one-lung ventilation (OLV) allowed for better surgical
      access and enabled complete resection of the lesion.

PMID- 15964891
TI  - Coagulopathy and blood component transfusion in trauma.
AB  - Trauma is a serious global health problem, accounting for approximately one in 10
      deaths worldwide. Uncontrollable bleeding accounts for 39% of trauma-related
      deaths and is the leading cause of potentially preventable death in patients with
      major trauma. While bleeding from vascular injury can usually be repaired
      surgically, coagulopathy-related bleeding is often more difficult to manage and
      may also mask the site of vascular injury. The causes of coagulopathy in patients
      with severe trauma are multifactorial, including consumption and dilution of
      platelets and coagulation factors, as well as dysfunction of platelets and the
      coagulation system. The interplay between hypothermia, acidosis and progressive
      coagulopathy, referred to as the 'lethal triad', often results in exsanguination.
      Current management of coagulopathy-related bleeding is based on blood component
      replacement therapy. However, there is a limit on the level of haemostasis that
      can be restored by replacement therapy. In addition, there is evidence that
      transfusion of red blood cells immediately after injury increases the incidence
      of post-injury infection and multiple organ failure. Strategies to prevent
      significant coagulopathy and to control critical bleeding effectively in the
      presence of coagulopathy may decrease the requirement for blood transfusion,
      thereby improving clinical outcome of patients with major trauma.

PMID- 15964892
TI  - Audit--using both the good and the bad news to improve patient care.

PMID- 15964893
TI  - Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold
      syndrome caused by mutations in the RECQL4 gene.
AB  - Baller-Gerold syndrome (BGS) is a rare autosomal recessive condition with radial
      aplasia/hypoplasia and craniosynostosis (OMIM 218600). Of >20 cases reported so
      far, a few appear atypical and have been reassigned to other nosologic entities,
      including Fanconi anaemia, Roberts SC phocomelia, and Pfeiffer syndromes after
      demonstration of corresponding cytogenetic or molecular abnormalities. Clinical
      overlap between BGS, Rothmund-Thomson syndrome (RTS), and RAPADILINO syndrome is
      noticeable. Because patients with RAPADILINO syndrome and a subset of patients
      with RTS have RECQL4 mutations, we reassessed two previously reported BGS
      families and found causal mutations in RECQL4 in both. In the first family, four
      affected offspring had craniosynostosis and radial defect and one of them
      developed poikiloderma. In this family, compound heterozygosity for a R1021W
      missense mutation and a g.2886delT frameshift mutation of exon 9 was found. In
      the second family, the affected male had craniosynostosis, radial ray defect,
      poikiloderma, and short stature. He had a homozygous splice site mutation (IVS17
      2A>C). In both families, the affected offspring had craniosynostosis, radial
      defects, and growth retardation, and two developed poikiloderma. Our results
      confirm that BGS in a subgroup of patients is due to RECQL4 mutations and could
      be integrated into a clinical spectrum that encompasses RTS and RAPADILINO
      syndrome.

PMID- 15964894
TI  - Impact of CFTR DeltaF508 mutation on prostaglandin E2 production and type IIA
      phospholipase A2 expression by pulmonary epithelial cells.
AB  - Cystic fibrosis (CF) is characterized by an exacerbated inflammatory pulmonary
      response with excessive production of inflammatory mediators. We investigated
      here the impact of cystic fibrosis transmembrane conductance regulator (CFTR)
      dysfunction on prostaglandin E2 (PGE2) production and type IIA secreted
      phospholipase A2 (sPLA2-IIA) expression. We show that both resting and LPS
      stimulated human respiratory epithelial cell line bearing DeltaF508 mutation on
      CFTR (CF cells) released more PGE2 than control cell line. This was accompanied
      by enhanced expression and activity of cyclooxygenase-2 in CF cells. PGE2 release
      was attenuated after experimentally induced retrafficking of the DeltaF508-CFTR
      at the plasma membrane. sPLA2-IIA expression occurred at higher levels in CF
      cells than in control cells and was enhanced by LPS and PGE2. Suppression of PGE2
      synthesis by aspirin led to an inhibition of LPS-induced sPLA2-IIA expression.
      Higher activation of NF-kappaB was observed in CF cells compared with control
      cells and was enhanced by LPS. However, addition of PGE2 or aspirin had no effect
      on NF-kappaB activation. LPS-induced sPLA2-IIA expression was reduced by an NF
      kappaB inhibitor. We suggest that the lack of the CFTR in the plasma membrane
      results in a PGE2 overproduction and an enhanced sPLA2-IIA expression. This
      expression is upregulated by NF-kappaB and amplified by PGE2 via a unidentified
      signaling pathway.

PMID- 15964895
TI  - Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in
      pulmonary arterial smooth muscle cells.
AB  - Chronic hypoxia (CH), caused by many lung diseases, results in pulmonary
      hypertension due, in part, to increased muscularity of small pulmonary vessels.
      Pulmonary arterial smooth muscle cell (PASMC) proliferation in response to growth
      factors requires increased intracellular pH (pHi) mediated by activation of
      Na+/H+ exchange (NHE); however, the effect of CH on PASMC pHi homeostasis is
      unknown. Thus we measured basal pHi and NHE activity and expression in PASMCs
      isolated from mice exposed to normoxia or CH (3 wk/10% O2). pHi was measured
      using the pH-sensitive fluorescent dye BCECF-AM. NHE activity was determined from
      Na+-dependent recovery from NH4-induced acidosis, and NHE expression was
      determined by RT-PCR and immunoblot. PASMCs from chronically hypoxic mice
      exhibited elevated basal pHi and increased NHE activity. NHE1 was the predominate
      isoform present in mouse PASMCs, and both gene and protein expression of NHE1 was
      increased following exposure to CH. Our findings indicate that exposure to CH
      caused increased pHi, NHE activity, and NHE1 expression, changes that may
      contribute to the development of pulmonary hypertension, in part, via pH
      dependent induction of PASMC proliferation.

PMID- 15964896
TI  - Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation
      and wound closure.
AB  - Antimicrobial peptides are endogenous antibiotics that directly inactivate
      microorganisms and in addition have a variety of receptor-mediated functions. LL
      37/hCAP-18 is the only cathelicidin found in humans and is involved in
      angiogenesis and regulation of the innate immune system. The aim of the present
      study was to characterize the role of the peptide LL-37 in the regulation of
      wound closure of the airway epithelium in the cell line NCI-H292 and primary
      airway epithelial cells. LL-37 stimulated healing of mechanically induced wounds
      in monolayers of the cell line and in differentiated primary airway epithelium.
      This effect was detectable at concentrations of 5 mug/ml in NCI-H292 and 1 mug/ml
      in primary cells. The effect of LL-37 on wound healing was dependent on the
      presence of serum. LL-37 induced cell proliferation and migration of NCI-H292
      cells. Inhibitor studies in the wound closure and proliferation assays indicated
      that the effects caused by LL-37 are mediated through epidermal growth factor
      receptor, a G protein-coupled receptor, and MAP/extracellular regulated kinase.
      In conclusion, LL-37 induces wound healing, proliferation, and migration of
      airway epithelial cells. The peptide is likely involved in the regulation of
      tissue homeostasis in the airways.

PMID- 15964897
TI  - Cellular mechanisms of thromboxane A2-mediated contraction in pulmonary veins.
AB  - Our objectives were to identify the relative contributions of [Ca2+]i and
      myofilament Ca2+ sensitivity in the pulmonary venous smooth muscle (PVSM)
      contractile response to the thromboxane A2 mimetic U-46619 and to assess the
      roles of PKC, tyrosine kinases (TK), and Rho-kinase (ROK) in that response. We
      tested the hypothesis that U-46619-induced contraction in PVSM is mediated by
      both increases in [Ca2+]i and myofilament Ca2+ sensitivity and that the PKC, TK,
      and ROK signaling pathways are involved. Isometric tension was measured in
      isolated endothelium-denuded (E-) canine pulmonary venous (PV) rings. In
      addition, [Ca2+]i and tension were simultaneously measured in fura-2-loaded E-
      PVSM strips. U-46619 (0.1 nM-1 microM) caused dose-dependent (P < 0.001)
      contraction in PV rings. U-46619 contraction was attenuated by inhibitors of L
      type voltage-operated Ca2+ channels (nifedipine, P < 0.001), inositol 1,4,5
      trisphosphate-mediated Ca2+ release (2-aminoethoxydiphenylborate, P < 0.001), PKC
      (bisindolylmaleimide I, P < 0.001), TK (tyrphostin A-47, P = 0.014), and ROK (Y
      27632, P = 0.008). In PV strips, U-46619 contraction was associated with
      increases in [Ca2+]i and myofilament Ca2+ sensitivity. Both Ca2+ influx and
      release mediated the early transient increase in [Ca2+]i, whereas the late
      sustained increase in [Ca2+]i only involved Ca2+ influx. Inhibition of both PKC
      and ROK (P = 0.006 and P = 0.002, respectively), but not TK, attenuated the U
      46619-induced increase in myofilament Ca2+ sensitivity. These results suggest
      that U-46619 contraction is mediated by Ca2+ influx, Ca2+ release, and increased
      myofilament Ca2+ sensitivity. The PKC, TK, and ROK signaling pathways are
      involved in U-46619 contraction.

PMID- 15964898
TI  - Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of
      chronic pulmonary hypertension in fetal and neonatal sheep.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is partly due to impaired
      nitric oxide (NO)-cGMP signaling. BAY 41-2272 is a novel direct activator of
      soluble guanylate cyclase, but whether this drug may be an effective therapy for
      PPHN is unknown. We hypothesized that BAY 41-2272 would cause pulmonary
      vasodilation in a model of severe PPHN. To test this hypothesis, we compared the
      hemodynamic response of BAY 41-2272 to acetylcholine, an endothelium-dependent
      vasodilator, and sildenafil, a selective inhibitor of PDE5 in chronically
      instrumented fetal lambs at 1 and 5 days after partial ligation of the ductus
      arteriosus. After 9 days, we delivered the animals by cesarean section to measure
      their hemodynamic responses to inhaled NO (iNO), sildenafil, and BAY 41-2272
      alone or combined with iNO. BAY 41-2272 caused marked pulmonary vasodilation, as
      characterized by a twofold increase in blood flow and a nearly 60% fall in PVR at
      day 1. Effectiveness of BAY 41-2272-induced pulmonary vasodilation increased
      during the development of pulmonary hypertension. Despite a similar effect at day
      1, the pulmonary vasodilator response to BAY 41-2272 was greater than sildenafil
      at day 5. At birth, BAY 41-2272 dramatically reduced PVR and augmented the
      pulmonary vasodilation induced by iNO. We concluded that BAY 41-2272 causes
      potent pulmonary vasodilation in fetal and neonatal sheep with severe pulmonary
      hypertension. We speculate that BAY 41-2272 may provide a novel treatment for
      severe PPHN, especially in newborns with partial response to iNO therapy.

PMID- 15964899
TI  - Wood smoke extract induces oxidative stress-mediated caspase-independent
      apoptosis in human lung endothelial cells: role of AIF and EndoG.
AB  - Although a link between toxic smoke and oxidant lung vascular injury has been
      indicated, the cellular mechanisms of smoke-induced injury to lung endothelial
      cells are unknown. We investigated oxidative stress and apoptosis induced by wood
      smoke extract (SE) in human pulmonary artery endothelial cells (HPAECs) and
      delineated their relationship. We found that SE increased intracellular reactive
      oxygen species (ROS), depleted intracellular glutathione, and upregulated Cu/Zn
      superoxide dismutase and heme oxygenase-1 (2 antioxidant enzymes), but it failed
      to alter the expression of catalase and glutathione peroxidase. In addition, SE
      promoted apoptosis as indicated by the external exposure of membrane
      phosphatidylserine, the loss of mitochondrial membrane potential, an increase in
      the level of Bax (a proapoptotic protein), and enhanced DNA fragmentation. This
      apoptosis was associated with mitochondrial-to-nuclear translocation of apoptosis
      inducing factor (AIF) and endonuclease G (EndoG) (2 apoptogenic proteins) but was
      independent of caspase cascade activation. Whereas N-acetylcysteine (an
      antioxidant) effectively reversed the SE-induced increase in ROS and depletion of
      glutathione, it also suppressed SE-induced nuclear translocation of either AIF or
      EndoG and prevented the enhanced DNA fragmentation that would have resulted from
      this. We conclude that 1) although SE upregulates Cu/Zn superoxide dismutase and
      heme oxygenase-1, it nevertheless increases intracellular oxidative stress in
      HPAECs, and 2) SE promotes oxidative stress-mediated caspase-independent HPAEC
      apoptosis that involves mitochondrial-to-nuclear translocation of AIF and EndoG.
      Thus modulations of the expression of antioxidant enzymes and the caspase
      independent apoptotic pathway are possible target choices for potential
      therapeutic regimes to treat smoke-induced lung injury.

PMID- 15964900
TI  - Cyclic mechanical strain increases reactive oxygen species production in
      pulmonary epithelial cells.
AB  - Overdistention of lung tissue during mechanical ventilation may be one of the
      factors that initiates ventilator-induced lung injury (VILI). We hypothesized
      that cyclic mechanical stretch (CMS) of the lung epithelium is involved in the
      early events of VILI through the production of reactive oxygen species (ROS).
      Cultures of an immortalized human airway epithelial cell line (16HBE), a human
      alveolar type II cell line (A549), and primary cultures of rat alveolar type II
      cells were cyclically stretched, and the production of superoxide (O2-) was
      measured by dihydroethidium fluorescence. CMS stimulated increased production of
      O2- after 2 h in each type of cell. 16HBE cells exhibited no significant
      stimulation of ROS before 2 h of CMS (20% strain, 30 cycles/min), and ROS
      production returned to control levels after 24 h. Oxidation of glutathione (GSH),
      a cellular antioxidant, increased with CMS as measured by a decrease in the ratio
      of the reduced GSH level to the oxidized GSH level. Strain levels of 10% did not
      increase O2- production in 16HBE cells, whereas 15, 20, and 30% significantly
      increased generation of O2-. Rotenone, a mitochondrial complex I inhibitor,
      partially abrogated the stretch-induced generation of O2- after 2 h CMS in 16HBE
      cells. NADPH oxidase activity was increased after 2 h of CMS, contributing to the
      production of O2-. Increased ROS production in lung epithelial cells in response
      to elevated stretch may contribute to the onset of VILI.

PMID- 15964901
TI  - Anionic poly(amino acid)s dissolve F-actin and DNA bundles, enhance DNase
      activity, and reduce the viscosity of cystic fibrosis sputum.
AB  - Bundles of F-actin and DNA present in the sputum of cystic fibrosis (CF) patients
      but absent from normal airway fluid contribute to the altered viscoelastic
      properties of sputum that inhibit clearance of infected airway fluid and
      exacerbate the pathology of CF. Previous strategies to remove these filamentous
      aggregates have focused on DNase to enzymatically depolymerize DNA to constituent
      monomers and gelsolin to sever F-actin to small fragments. The high densities of
      negative surface charge on DNA and F-actin suggest that the bundles of these
      filaments, which alone exhibit a strong electrostatic repulsion, may be
      stabilized by multivalent cations such as histones, antimicrobial peptides, and
      other positively charged molecules prevalent in airway fluid. This study reports
      that bundles of DNA or F-actin formed after addition of histone H1 or lysozyme
      are efficiently dissolved by soluble multivalent anions such as polymeric
      aspartate or glutamate. Addition of poly-aspartate or poly-glutamate also
      disperses DNA and actin-containing bundles in CF sputum and lowers the elastic
      moduli of these samples to levels comparable to those obtained after treatment
      with DNase I or gelsolin. Addition of poly-aspartic acid also increased DNase
      activity when added to samples containing DNA bundles formed with histone H1.
      When added to CF sputum, poly-aspartic acid significantly reduced the growth of
      bacteria, suggesting activation of endogenous antibacterial factors. These
      findings suggest that soluble multivalent anions have potential alone or in
      combination with other mucolytic agents to selectively dissociate the large
      bundles of charged biopolymers that form in CF sputum.

PMID- 15964902
TI  - Phosphatidylinositol 3-kinase and ERK1/2 are not involved in adenosine A1, A2A or
      A3 receptor-mediated preconditioning in rat ventricle strips.
AB  - Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated
      kinase 1 and 2 (ERK1/2) and phosphatidylinositol 3-kinase (PI3-kinase)/protein
      kinase B (PKB; also known as Akt) are important antiapoptotic signalling pathways
      which have recently been implicated in cardioprotection. However, at present the
      involvement of ERK1/2 and PI3-kinase/PKB in adenosine receptor-mediated
      cardioprotection is poorly understood. In this study we used isolated rat right
      ventricular strips, contracted by electrical-field stimulation, in order to
      investigate the role of ERK1/2 and PI3-kinase/PKB in adenosine receptor-induced
      cardioprotection. Ventricle strips were pretreated for 2 min with the agonists
      adenosine (non-selective), CPA (A1 selective), CGS 21680 (A2A selective) and Cl
      IB-MECA (A3 selective) before 30 min hypoxia followed by 30 min reoxygenation.
      Each agonist significantly improved posthypoxic percentage contraction recovery
      compared to control strips. Similarly hypoxic preconditioning (10 min hypoxia
      followed by 20 min reoxygenation) significantly improved posthypoxic percentage
      contraction recovery compared to non-preconditioned strips. The selective
      adenosine receptor antagonists DPCPX (A1), ZM 241385 (A2A) and MRS 1220 (A3)
      attenuated cardioprotection induced by CPA, CGS 21680 and Cl-IB-MECA,
      respectively. Pre-incubation (30 min) of ventricle strips with the MEK1 inhibitor
      PD 98059 (50 microM) or the PI3-kinase inhibitor wortmannin (100 nM)
      significantly reduced posthypoxic percentage contraction recovery induced by
      hypoxic preconditioning. In contrast, PD 98059 and wortmannin had no significant
      effect on cardioprotection induced by CPA, Cl-IB-MECA or CGS 21680. Overall these
      data indicate that although selective A1, A2A and A3 adenosine receptor agonists
      induce preconditioning in rat right ventricular strips the effects are
      independent of ERK1/2- and PI3-kinase-dependent pathways. In contrast ERK1/2 and
      PI3-kinase-dependent pathways do appear to be involved in early hypoxic
      preconditioning.

PMID- 15964903
TI  - Inducible trans-activation of plastid transgenes: expression of the R. eutropha
      phb operon in transplastomic tobacco.
AB  - Deleterious effects of constitutive transgene expression can occur if gene
      products are harmful to the transformed plant. Constraints such as growth
      inhibition and male sterility have been observed in plastid transformants
      containing the phb operon encoding the genes required for the production of the
      polyester polyhydroxybutyric acid (PHB). In order to induce PHB synthesis in
      tobacco in a well-timed manner, we have constructed a trans-activation system to
      regulate transcription of the phb operon in plastids. This system consists of a
      nuclear-located, ethanol-inducible T7RNA polymerase (T7RNAP) which is targeted to
      plastids harboring the phb operon under control of T7 regulatory elements.
      Following treatment with 5% ethanol, moderate induction of PHB synthesis was
      found. PHB amounts reached 1,383 ppm in dry weight, and an overall background
      activity of 171 ppm was measured in uninduced tissues. On the transcriptional
      level, T7RNAP induction was proven and we found that the phb operon is
      transcribed into at least two mRNAs. Without ethanol induction, development of
      flowers and fertile seeds was possible. Thus, the main problem of inhibitory
      transgene expression was solved. Our results show that this inducible trans
      activation system could serve as an alternative to constitutive expression of
      transgenes in the plastome.

PMID- 15964904
TI  - An Arabidopsis protein with a novel calcium-binding repeat sequence interacts
      with TONSOKU/MGOUN3/BRUSHY1 involved in meristem maintenance.
AB  - TONSOKU(TSK)/MGOUN3/BRUSHY1 from Arabidopsis thaliana, which plays an important
      role in the maintenance of meristem organization, contains an LGN repeat motif
      similar to that found in animal proteins involved in asymmetric cell division.
      One protein that interacts with the LGN motif of TSK in a yeast two-hybrid
      screen, TSK-associating protein 1 (TSA1), contains a 10-fold repeat of a unique
      41 amino acid sequence. The repeat sequence, with a glutamic acid-phenylalanine
      glutamic acid (EFE) conserved core sequence, is enriched with acidic amino acids.
      TSA1 also contains an N-terminal putative signal peptide and it interacts with
      the LGN motif of TSK through a C-terminal region separated from the EFE repeats
      by a putative membrane-spanning region. The recombinant protein consisting of EFE
      repeats was rich in alpha-helical structure and possessed Ca2+-binding activity.
      Unlike nuclear localization of TSK, the TSA1 fused with green fluorescent protein
      (GFP) expressed in tobacco BY-2 cells was localized in small cytoplasmic vesicles
      during interphase. However, cellular localization of both TSA1-GFP and GFP-TSK
      changed dynamically during mitosis. In particular, both GFP-TSK and TSA1-GFP were
      concentrated in limited areas that are close to the ends of spindle microtubules
      ahead of separating chromatids. These results are discussed in terms of the
      possible involvement of TSK and TSA1 in mitosis.

PMID- 15964905
TI  - Multiple regulatory elements contribute to the vascular-specific expression of
      the rice HD-Zip gene Oshox1 in Arabidopsis.
AB  - The primary vascular tissues of plants differentiate from a single precursor
      tissue, the procambium. The role of upstream regulatory sequences in the
      transcriptional control of early vascular-specific gene expression is largely
      unknown. The onset of expression of the rice homeodomain-leucine zipper (HD-Zip)
      gene Oshox1 marks procambial cells that have acquired their distinctive
      anatomical features but do not yet display any overt signs of terminal vascular
      differentiation. The expression pattern of Oshox1 in rice appears to be mainly
      controlled by the activity of the 1.6 kb upstream promoter region. Here, we show
      that the Oshox1 promoter directs vascular, auxin- and sucrose-responsive reporter
      gene expression in Arabidopsis plants in a fashion comparable with that in rice.
      This is the case not only during normal development but also upon experimental
      manipulation, suggesting that the cis-acting regulatory elements that are
      instrumental in Oshox1 expression pattern are conserved between rice and
      Arabidopsis. Finally, through analysis of reporter gene expression profiles
      conferred by progressive 5' deletions of the Oshox1 promoter in transgenic
      Arabidopsis, we have identified upstream regulatory regions required for auxin
      and sucrose inducibility, and for cell type-, tissue- and organ-specific aspects
      of Oshox1 expression. Our study suggests that Oshox1 embryonic vascular
      expression is mainly achieved through suppression of expression in non-vascular
      tissues.

PMID- 15964906
TI  - High magnification chromoscopic colonoscopy or high frequency 20 MHz mini probe
      endoscopic ultrasound staging for early colorectal neoplasia: a comparative
      prospective analysis.
AB  - BACKGROUND: Successful endoscopic management of early colorectal cancer using
      endoscopic mucosal resection requires the mandatory prediction of invasive depth
      and lymph node metastasis. Previous data using the Nagata crypt types Vn(B)/(C)
      as clinical indicators of T2/N+ disease have shown low specificity (50%) with a
      tendency to over stage lesions. New mini probe ultrasound "through the scope"
      imaging permits staging of lesions proximal to the rectum using direct endoscopic
      visualisation. AIM: To compare the staging accuracy of the Nagata crypt type V
      with mini probe high frequency 20 MHz endoscopic ultrasound. METHODS: Sixty two
      patients with a Paris type II flat cancer were imaged using magnification
      colonoscopy followed by 20/12.5 MHz ultrasound in a "back to back" design.
      Crystal violet staining (0.05%) at 100x magnification permitted Nagata crypt
      criteria to be defined. Submucosal deep invasion (sm3+) was defined at ultrasound
      by the presence or absence of a disrupted third sonographic layer. Predicted
      T0/1:N0 lesions were resected using endoscopic mucosal resection with the
      remaining referred for surgery. Ultrasound and magnification staging were then
      compared with the resected histopathological specimens. RESULTS: One patient was
      excluded from the study due to poor bowel preparation. Fifty two lesions from 52
      patients therefore met inclusion criteria (12 sm1/13 sm2/27 sm3+). Ultrasound (20
      MHz) was significantly more accurate for invasive depth staging compared with
      Nagata stage (p<0.0001) (overall accuracy 93% and 59%, respectively). The
      sensitivity for lymph node metastasis detection using ultrasound and
      magnification was 80% and 31%, respectively (p<0.001). The negative predictive
      value of ultrasound for invasive depth was better than that observed using
      magnification (88%/47%, respectively). The prevalence of nodal disease overall
      was 19% (10/52), with 80% (8/10) node positive lesions occurring in the sm3+
      lesion group. CONCLUSIONS: High frequency 20 MHz ultrasound is superior to
      magnification alone when differentiating T1/2 disease with a high positive
      predictive value for sm3 differentiation. Sm3+ invasion was associated with nodal
      metastasis.

PMID- 15964907
TI  - Commentary: Vaginal discharge and stress: a commentary on directions of
      influence.

PMID- 15964908
TI  - Cohort profile: the Hertfordshire cohort study.

PMID- 15964909
TI  - Cohort profile: The Boyd Orr lifegrid sub-sample--medical sociology study of life
      course influences on early old age.

PMID- 15964910
TI  - Cohort profile: The Boyd Orr cohort--an historical cohort study based on the 65
      year follow-up of the Carnegie Survey of Diet and Health (1937-39).

PMID- 15964911
TI  - Cohort patterns in mortality trends among the elderly in seven European
      countries, 1950-99.
AB  - BACKGROUND: Secular trends in old-age mortality are of crucial importance to
      population ageing. For the understanding and prediction of these trends, it is
      important to determine whether birth cohort effects, i.e. long-lasting effects of
      exposures earlier in life, are important in determining mortality trends up to
      old age. This study aimed to identify and describe cohort patterns in trends in
      mortality among the elderly (>60 years of age) in seven European countries.
      METHODS: A standard age-period-cohort analysis was applied to all-cause and cause
      specific mortality data by 5-year age groups and sex, for Denmark, England and
      Wales, Finland, France, The Netherlands, Norway, and Sweden, in the period 1950
      99. RESULTS: Cohort patterns were identified in all countries, for both the sexes
      and virtually all causes of death. They strongly influenced the trends in all
      cause mortality among Danish, Dutch, and Norwegian men, and the trends in
      mortality from infectious diseases, lung cancer (men only), prostate cancer,
      breast cancer, and chronic obstructive pulmonary disease (COPD). All-cause
      mortality decline stagnated among Danish, Dutch, and Norwegian male birth cohorts
      born between 1890 and 1915, among French men born after 1920, and among women
      from all countries born after 1920. Where all-cause mortality decline stagnated,
      cohort patterns in mortality from lung cancer, COPD, and to a lesser extent
      ischaemic heart diseases, were unfavourable as well. For infectious diseases,
      stomach cancer, and cerebrovascular diseases, mortality increased among cohorts
      born before 1890, and decreased strongly thereafter. CONCLUSIONS: Cohort effects
      related to factors such as living conditions in childhood and smoking in
      adulthood were important in determining the recent trends in mortality among the
      elderly in seven European countries.

PMID- 15964912
TI  - Patterns of dynamic hyperinflation during exercise and recovery in patients with
      severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: Not all patients with severe chronic obstructive pulmonary disease
      (COPD) progressively hyperinflate during symptom limited exercise. The pattern of
      change in chest wall volumes (Vcw) was investigated in patients with severe COPD
      who progressively hyperinflate during exercise and those who do not. METHODS:
      Twenty patients with forced expiratory volume in 1 second (FEV(1)) 35 (2)%
      predicted were studied during a ramp incremental cycling test to the limit of
      tolerance (Wpeak). Changes in Vcw at the end of expiration (EEVcw), end of
      inspiration (EIVcw), and at total lung capacity (TLCVcw) were computed by
      optoelectronic plethysmography (OEP) during exercise and recovery. RESULTS: Two
      significantly different patterns of change in EEVcw were observed during
      exercise. Twelve patients had a progressive significant increase in EEVcw during
      exercise (early hyperinflators, EH) amounting to 750 (90) ml at Wpeak. In
      contrast, in all eight remaining patients EEVcw remained unchanged up to 66%
      Wpeak but increased significantly by 210 (80) ml at Wpeak (late hyperinflators,
      LH). Although at the limit of tolerance the increase in EEVcw was significantly
      greater in EH, both groups reached similar Wpeak and breathed with a tidal EIVcw
      that closely approached TLCVcw (EIVcw/TLCVcw 93 (1)% and 93 (3)%, respectively).
      EEVcw was increased by 254 (130) ml above baseline 3 minutes after exercise only
      in EH. CONCLUSIONS: Patients with severe COPD exhibit two patterns during
      exercise: early and late hyperinflation. In those who hyperinflate early, it may
      take several minutes before the hyperinflation is fully reversed after
      termination of exercise.

PMID- 15964914
TI  - Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Because oxidative stress affects muscle function, the underlying
      mechanism to explain exercise induced peripheral muscle oxidative stress in
      patients with chronic obstructive pulmonary disease (COPD) is clinically
      relevant. This study investigated whether chronic hypoxaemia in COPD worsens
      peripheral muscle oxidative stress and whether an abnormal muscle inflammatory
      process is associated with it. METHODS: Nine chronically hypoxaemic and nine non
      hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy
      specimens were taken from the vastus lateralis muscle before and 48 hours after
      exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin
      and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins.
      Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis
      factor (TNF)-alpha levels. RESULTS: When both groups were taken together,
      arterial oxygen pressure was positively correlated with quadriceps endurance time
      (n = 18, r = 0.57; p < 0.05). At rest, quadriceps lipofuscin inclusions were
      significantly greater in hypoxaemic patients than in non-hypoxaemic patients (2.9
      (0.2) v 2.0 (0.3) inclusions/fibre; p < 0.05). Exercise induced a greater
      increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non
      hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%,
      respectively, both p = 0.01). Neutrophil levels were significantly higher in
      hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2)
      counts per fibre x 10(-3); p < 0.05). Exercise did not alter muscle neutrophil
      levels in either group. Muscle TNF-alpha was not detected at baseline or after
      exercise. CONCLUSION: Chronic hypoxaemia was associated with lower quadriceps
      endurance time and worsened muscle oxidative stress at rest and after exercise.
      Increased muscle neutrophil levels could be a source of the increased baseline
      oxidative damage. The involvement of a muscle inflammatory process in the
      exercise induced oxidative stress of patients with COPD remains to be shown.

PMID- 15964915
TI  - Estrogenic regulation of tissue factor and tissue factor pathway inhibitor in
      platelets.
AB  - Oral estrogen treatment increases thrombotic risk. Tissue factor (TF), tissue
      factor pathway inhibitor (TFPI), and platelet interaction with leukocytes are
      important determinants of thrombogenesis. Therefore, the present study was
      designed to define and compare platelet TF and TFPI mRNA and adhesion protein
      expression in platelets derived from animals treated with different types of oral
      estrogens. Ovariectomized pigs were treated with 17beta-estradiol (2 mg/day),
      conjugated equine estrogen (CEE; 0.625 mg/day), or raloxifene (60 mg/day) for 4
      wk. Compared with intact animals, ovariectomy and treatment differentially
      affected populations of leukocytes: neutrophils decreased whereas lymphocytes
      increased significantly 4 wk after ovariectomy and with 17beta-estradiol and CEE
      treatments; eosinophils increased only with 17beta-estradiol treatment. Content
      of TF protein increased in platelets from 17beta-estradiol- and raloxifene
      treated pigs, whereas TF mRNA was detected only in platelets from 17beta
      estradiol- and CEE treated pigs. TFPI mRNA increased in platelets after
      ovariectomy and estrogen treatment. Only a trace of TFPI protein was detected,
      but a higher-molecular-mass protein was observed in all treatment groups.
      Expression of CD40 and CD40 ligand increased with ovariectomy and decreased with
      17beta-estradiol and CEE treatments more than with raloxifene. The ratio of
      activated to basal P-selectin expression decreased with ovariectomy and increased
      with raloxifene treatments. These results suggest that estrogenic formulations
      may affect individual thrombotic risk by different mechanisms that regulate TF
      and platelet-leukocytic interactions. These studies provide the rationale for
      evaluation of interactions among platelets and TF and TFPI expression on thrombin
      generation during estrogen treatment in humans.

PMID- 15964916
TI  - Regulation of angiotensin-converting enzyme production by nicotine in human
      endothelial cells.
AB  - Nicotine, a component of cigarette smoke, has been implicated in the pathogenesis
      of cardiovascular disease. We examined whether nicotine regulates angiotensin
      converting enzyme (ACE), an enzyme that plays an important role in the
      pathophysiology of atherosclerosis and hypertension. Human umbilical cord vein
      endothelial cells were treated with nicotine (0.1-1 microM) alone or in
      combination with vascular endothelial growth factor (VEGF; 0.5 nM) or GF-109203X
      (GFX; 2.5 microM). The amount of ACE in intact endothelial cells was measured by
      an inhibitor-binding assay method, and ACE mRNA levels were quantified using
      LightCycler technology. Phosphorylated PKC levels were measured by Western
      immunoblotting. Nicotine did not modulate basal ACE production but significantly
      potentiated VEGF-induced ACE upregulation. Treatment of endothelial cells with
      the PKC inhibitor GFX totally blocked VEGF- and nicotine-induced ACE
      upregulation. VEGF induced PKC phosphorylation, which was potentiated by
      cotreatment with nicotine. We conclude that nicotine significantly potentiated
      VEGF-induced ACE upregulation. This effect was probably mediated by PKC
      phosphorylation. The interaction of nicotine with VEGF in ACE induction may
      contribute to the pathogenesis of smoking-related cardiovascular disease.

PMID- 15964917
TI  - Novel determinant of PKC-epsilon anchoring at cardiac Z-lines.
AB  - The Z-line represents a critical link between the transverse tubule network and
      cytoskeleton of cardiac cells with a role in anchoring structural proteins, ion
      channels, and signaling molecules. Protein kinase C-epsilon (PKC-epsilon)
      regulates cardiac excitability, cardioprotection, and growth, possibly as a
      consequence of translocation to the Z-line/T tubule region. To investigate the
      mechanism of PKC-epsilon translocation, fragments of its NH2-terminal 144-amino
      acid variable domain, epsilonV1, were fused with green fluorescent protein and
      evaluated by quantitative Fourier image analysis of decorated myocytes. Deletion
      of 23 amino acids from the NH2-terminus of epsilonV1, including an EAVSLKPT motif
      important for binding to a receptor for activated C kinase (RACK2), reduced but
      did not abolish Z-line binding. Further deletions of up to 84 amino acids from
      the NH2-terminus of epsilonV1 also did not prevent Z-line decoration. However,
      deletions of residues 85-144 from the COOH-terminus strongly reduced Z-line
      binding. COOH-terminal deletions caused 2.5-fold greater loss of binding energy
      (deltadeltaG) than did NH2-terminal deletions. Synthetic peptides derived from
      these regions modulated epsilonV1 binding and cardiac myocyte function, but also
      revealed considerable heterogeneity within populations of adult cardiac myocytes.
      The COOH-terminal subdomain important for Z-line anchoring maps to a surface in
      the epsilonV1 crystal structure that complements the eight-amino acid RACK2
      binding site and two previously identified membrane docking motifs. PKC-epsilon
      anchoring at the cardiac Z-line/T tubule appears to rely on multiple points of
      contact probably involving protein-lipid and protein-protein interactions.

PMID- 15964918
TI  - Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell
      proliferative dysfunction.
AB  - Diabetes mellitus is a major risk factor for the development of vascular
      complications. We hypothesized that hyperglycemia decreases endothelial cell (EC)
      proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt
      signaling pathways. We cultured human umbilical vein ECs (HUVEC) in 5, 20, or 40
      mM d-glucose. Cells grown in 5, 20, and 40 mM mannitol served as a control for
      osmotic effects. We measured EC proliferation for up to 15 days. We assessed
      apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed
      cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt
      by Western blot analysis, and measured Akt kinase activity using a GSK fusion
      protein. HUVEC proliferation was also tested in the presence of pharmacological
      inhibitors of PI3k-Akt (wortmannin and LY294002) and after transfection with a
      constitutively active Akt mutant. ECs in media containing 5 mM d-glucose
      (control) exhibited log-phase growth on days 7-10. d-Glucose at 20 and 40 mM
      significantly decreased proliferation versus control (P < 0.05 for both), whereas
      mannitol did not impair EC proliferation. Apoptosis increased significantly in
      HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased
      tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity
      relative to control 5 mM d-glucose. Pharmacological inhibition of PI3k-Akt
      resulted in a dose-dependent decrease in EC proliferation. Transfection with a
      constitutively active Akt mutant protected ECs by enhancing proliferation when
      grown in 20 and 40 mM d-glucose. We conclude that d-glucose regulates Akt
      signaling through threonine phosphorylation of Akt and that hyperglycemia
      impaired PI3k-Akt signaling may promote EC proliferative dysfunction in diabetes.

PMID- 15964919
TI  - Effective permeability of hydrophilic substances through walls of lymph vessels:
      roles of endothelial barrier.
AB  - The wall effective permeability of hydrophilic substances labeled with
      fluorescent dyes was evaluated in an isolated cannulated rat single lymph vessel
      through a videomicroscope system. Sodium fluorescein (NaFl; 332 mol wt) and FITC
      dextrans (4,400, 12,000, and 71,200 mol wt) were administered into the
      intraluminal space of the lymph vessels and then excited by a Xenon lamp. Changes
      in the fluorescence intensity of the dyes were continuously measured by a silicon
      intensified target camera through appropriate filters. The net flux of each dye
      in the wall of the lymph vessels was calculated by the relationship between the
      fluorescence intensity and the concentration of the dyes. NaFl and FITC-dextran
      4,400 in the intraluminal space of isolated rat lymph vessels significantly
      penetrated the wall of the lymph vessels. FITC-dextran 12,000 in the intraluminal
      space of isolated rat lymph vessels slightly passed through the lymphatic wall,
      whereas FITC-dextran 71,200 did not penetrate the wall. Intraluminal pressures
      ranging from 4 to 8 cm H(2)O did not significantly affect the net flux of dyes
      used in the present study. After administration of 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate into the lymph vessels, the
      net flux of FITC-dextran 4,400 and 12,000 but not 71,200 was augmented
      significantly. These results suggest that small molecular hydrophilic substances
      (< or =4,400) are permeable from the intraluminal to extraluminal space of
      isolated lymph vessels and that the endothelial cell surface structure may play a
      barrier role in the effective permeability of large molecular hydrophilic
      substances (4,400 to 12,000) through the wall of the lymph vessels.

PMID- 15964920
TI  - Reversal of delayed vasospasm by an inhibitor of the synthesis of 20-HETE.
AB  - This study characterized the time course of changes in cerebral blood flow (CBF)
      and vascular diameter in a dual-hemorrhage model of subarachnoid hemorrhage (SAH)
      in rats and examined whether acute blockade of the synthesis of 20
      hydroxyeicosatetraenoic acid (20-HETE) with N-(3-chloro-4-morpholin-4-yl)phenyl
      N'-hydroxyimido formamide (TS-011) can reverse delayed vasospasm in this model.
      Rats received an intracisternal injection of blood (0.4 ml) on day 0 and a second
      injection 2 days later. CBF was sequentially measured using laser-Doppler
      flowmetry, and the diameters of the cerebral arteries were determined after
      filling the cerebral vasculature with a casting compound. CBF fell to 67% of
      control after the first intracisternal injection of blood but returned to a value
      near control 24 h later. CBF again fell to 63% of control after a second
      intracisternal injection of blood and remained 30% below control for 5 days. The
      fall in CBF after the second intracisternal injection of blood was associated
      with a sustained 30% reduction in the diameters of the middle cerebral, posterior
      communicating, and basilar arteries. Acute blockade of the synthesis of 20-HETE
      with TS-011 (0.1 mg/kg i.v.), 5 days after the second SAH, increased the
      diameters of the cerebral arteries, and CBF returned to control. These results
      indicate that the rats develop delayed vasospasm after induction of the dual
      hemorrhage model of SAH and that blockade of the synthesis of 20-HETE fully
      reverses cerebral vasospasm in this model. They also implicate 20-HETE in the
      development and maintenance of delayed cerebral vasospasm.

PMID- 15964922
TI  - Three-dimensional systolic kinematics of the right ventricle.
AB  - The right ventricle (RV) of the heart is responsible for pumping blood to the
      lungs. Its kinematics are not as well understood as that of the left ventricle
      (LV) due to its thin wall and asymmetric geometry. In this study, the combination
      of tagged MRI and three-dimensional (3-D) image-processing techniques was used to
      reconstruct 3-D RV-LV motion and deformation. The reconstructed models were used
      to quantify the 3-D global and local deformation of the ventricles in a set of
      normal subjects. When compared with the LV, the RV exhibited a similar twisting
      pattern, a more longitudinal strain pattern, and a greater amount of
      displacement.

PMID- 15964921
TI  - Nitric oxide increases carbon monoxide production by piglet cerebral
      microvessels.
AB  - Carbon monoxide (CO) and nitric oxide (NO) can be involved in the regulation of
      cerebral circulation. Inhibition of production of either one of these gaseous
      intercellular messengers inhibits newborn pig cerebral arteriolar dilation to the
      excitatory amino acid glutamate. Glutamate can increase NO production. Therefore,
      the present study tests the hypothesis that NO, which is increased by glutamate,
      stimulates the production of CO by cerebral microvessels. Experiments used
      freshly isolated cerebral microvessels from piglets that express only heme
      oxygenase-2 (HO-2). CO production was measured by gas chromatography-mass
      spectrometry. Although inhibition of nitric oxide synthase (NOS) with N(omega)
      nitro-l-arginine (l-NNA) did not alter basal HO-2 catalytic activity or CO
      production, l-NNA blocked glutamate stimulation of HO-2 activity and CO
      production. Furthermore, the NO donor sodium nitroprusside mimicked the actions
      of glutamate on HO-2 and CO production. The action of NO appears to be via cGMP
      because 8-bromo-cGMP mimics and 1H-[1,2,4]oxadiazole-[4,3-a]quinoxalin-1-one
      (ODQ) blocks glutamate stimulation of CO production and HO-2 catalytic activity.
      Inhibitors of neither casein kinase nor phosphotidylinositol 3-kinase altered HO
      2 catalytic activity. Conversely, inhibition of calmodulin with calmidazolium
      chloride blocked glutamate stimulation of CO production and reduced HO-2
      catalytic activity. These data suggest that glutamate may activate NOS producing
      NO that leads to CO synthesis via a cGMP-dependent elevation of HO-2 catalytic
      activity. These results are consistent with the findings in vivo that either HO
      or NOS inhibition blocks cerebrovascular dilation to glutamate in piglets.

PMID- 15964923
TI  - Functional adaptation and remodeling of pulmonary artery in flow-induced
      pulmonary hypertension.
AB  - Patients with left-to-right shunt congenital heart disease may develop pulmonary
      hypertension. Perioperative mortality of these patients is high due to abnormal
      vasoreactivity of the pulmonary artery (PA). We studied the changes in the PA
      induced by high pulmonary blood flow in rats with aortocaval fistula. Eight weeks
      after surgery, morphological changes of the PA were studied and vasomotor
      function was assessed by isometric force recording. Expression of endothelial
      nitric oxide (NO) synthase (eNOS), VEGF, and cyclooxygenase-2 (COX-2) proteins
      and levels of cGMP in the PA were analyzed. Rats with high pulmonary blood flow
      developed pulmonary hypertension, medial thickening, and increasing of internal
      elastic lamina and basement membrane in the PA. When compared with sham-operated
      animals, rats with fistula had significantly increased contractions in the PA,
      whereas relaxations to acetylcholine and NO donor were reduced. Concentrations of
      cGMP were reduced in the PA of rats with pulmonary hypertension (18.4 +/- 3.3 vs.
      9.4 +/- 1.7 pmol/mg protein; P = 0.04). The altered vasomotor function was
      normalized by treatment with indomethacin. The PA of rats with fistula expressed
      higher levels of eNOS, phosphorylated eNOS, and COX-2. Sustained high PA blood
      flow in rats causes pulmonary hypertension that is morphologically and
      functionally identical with patients with flow-induced pulmonary hypertension.
      Abnormal vasomotor function of the PA in these animals appears to be mediated by
      reduced availability and the biological effect of endogenous NO and the high
      production of vasoconstrictor prostanoids. Increased eNOS and phosphorylated eNOS
      are most likely the adaptive changes in response to an increase in PA pressure
      secondary to high blood flow.

PMID- 15964924
TI  - Electromechanics of paced left ventricle simulated by straightforward
      mathematical model: comparison with experiments.
AB  - Intraventricular synchrony of cardiac activation is important for efficient pump
      function. Ventricular pacing restores the beating frequency but induces more
      asynchronous depolarization and more inhomogeneous contraction than in the normal
      heart. We investigated whether the increased inhomogeneity in the left ventricle
      can be described by a relatively simple mathematical model of cardiac
      electromechanics, containing normal mechanical and impulse conduction properties.
      Simulations of a normal heartbeat and of pacing at the right ventricular apex
      (RVA) were performed. All properties in the two simulations were equal, except
      for the depolarization sequence. Simulation results of RVA pacing on local
      depolarization time and systolic midwall circumferential strain were compared
      with those measured in dogs, using an epicardial sock electrode and MRI tagging,
      respectively. We used the same methods for data processing for simulation and
      experiment. Model and experiment agreed in the following aspects. 1) Ventricular
      pacing decreased systolic pressure and ejection fraction relative to natural
      sinus rhythm. 2) Shortening during ejection and stroke work declined in early
      depolarized regions and increased in late depolarized regions. 3) The relation
      between epicardial depolarization time and systolic midwall circumferential
      strain was linear and similar for the simulation (slope = -3.80 +/- 0.28 s(-1),
      R2 = 0.87) and the experiments [slopes for 3 animals -2.62 +/- 0.43 s(-1) (R2 =
      0.59), -2.97 +/- 0.38 s(-1) (R2 = 0.69), and -4.44 +/- 0.51 s(-1) (R2 = 0.76)].
      We conclude that our model of electromechanics is suitable to simulate
      ventricular pacing and that the apparently complex events observed during pacing
      are caused by well-known basic physiological processes.

PMID- 15964925
TI  - Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary
      vascular bed of guinea pig hearts.
AB  - Atrial natriuretic peptide (ANP) is reported to enhance vascular permeability in
      vivo. Our aim was to evaluate the impact of ANP on coronary extravasation of
      fluids and macromolecules and on the integrity of the endothelial glycocalyx.
      Isolated guinea pig hearts (n = 6/group) were perfused with Krebs-Henseleit
      buffer in a Langendorff mode. A 6% hydroxyethyl starch (HES) solution was infused
      into the coronary system for 20 min without (Control group) and simultaneously
      with (ANP group) ANP at 10(-9) M. In two further series, the glycocalyx was
      enzymatically degraded by means of heparinase (Hep) application (10 IU over 15
      min), followed again by the infusion of HES in the absence (Hep group) and
      presence (ANP+Hep group) of ANP. Net fluid filtration, extravasation of HES,
      electron microscopic visualization of the glycocalyx, and quantification of
      shedding of syndecan-1, a component of the glycocalyx, were determined. An
      increase in fluid leak was observed in ANP, ANP+Hep, and Hep hearts [+29%, +31%,
      +14%, respectively; a decrease was observed in Control hearts (-13%)]. Similarly,
      an accelerated extravasation of colloid was observed in these three groups.
      Coronary release of syndecan-1 increased 9- to 18-fold during infusion of ANP.
      Electron microscopy revealed a dramatic degradation of the glycocalyx after ANP.
      These results indicate that the endothelial glycocalyx serves as a barrier to
      transmural exchange of fluid and colloid in the coronary vascular system. ANP
      causes rapid shedding of individual components of the glycocalyx and
      histologically detectable degradation. Thus the permeability-increasing effect of
      ANP may be at least partially related to changes in the integrity of the
      endothelial glycocalyx.

PMID- 15964926
TI  - Splanchnic hyperemia and hypervolemia during Valsalva maneuver in postural
      tachycardia syndrome.
AB  - Prior work demonstrated dependence of the change in blood pressure during the
      Valsalva maneuver (VM) on the extent of thoracic hypovolemia and splanchnic
      hypervolemia. Thoracic hypovolemia and splanchnic hypervolemia characterize
      certain patients with postural tachycardia syndrome (POTS) during orthostatic
      stress. These patients also experience abnormal phase II hypotension and phase IV
      hypertension during VM. We hypothesize that reduced splanchnic arterial
      resistance explains aberrant VM results in these patients. We studied 17 POTS
      patients aged 15-23 yr with normal resting peripheral blood flow by strain gauge
      plethysmography and 10 comparably aged healthy volunteers. All had normal blood
      volumes by dye dilution. We assessed changes in estimated thoracic, splanchnic,
      pelvic-thigh, and lower leg blood volume and blood flow by impedance
      plethysmography throughout VM performed in the supine position. Baseline
      splanchnic blood flow was increased and calculated arterial resistance was
      decreased in POTS compared with control subjects. Splanchnic resistance decreased
      and flow increased in POTS subjects, whereas splanchnic resistance increased and
      flow decreased in control subjects during stage II of VM. This was associated
      with increased splanchnic blood volume, decreased thoracic blood volume,
      increased heart rate, and decreased blood pressure in POTS. Pelvic and leg
      resistances were increased above control and remained so during stage IV of VM,
      accounting for the increased blood pressure overshoot in POTS. Thus splanchnic
      hyperemia and hypervolemia are related to excessive phase II blood pressure
      reduction in POTS despite intense peripheral vasoconstriction. Factors other than
      autonomic dysfunction may play a role in POTS.

PMID- 15964927
TI  - Electrophysiological effects of O2*- on the plasma membrane in vascular
      endothelial cells.
AB  - Vascular dysfunction is a hallmark of many diseases, including coronary heart
      disease, stroke, and diabetes. The underlying mechanisms of these disorders are
      intimately associated with an increase in oxidative stress and excess generation
      of reactive oxygen species. Here, we report that the anionic free radical,
      superoxide (O2*- ), directly affects the function of ion channels in vascular
      endothelial cells. Vascular endothelial cells were exposed to O2*- under
      physiological, symmetrical chloride and chloride-free conditions. Superoxide was
      generated from the reaction of xanthine (0.2 mM) and xanthine oxidase (0.1, 1,
      and 10 mU/ml) while its effects were determined with the whole cell mode of the
      patch-clamp technique. Inhibitors of K+ and Cl- channels were used to determine
      the role of these ion channels in mediating the electrophysiological effects of
      superoxide. The addition of O2*- caused a dose-dependent depolarization of
      endothelial cells and activation of the whole cell current. Activation of
      superoxide-dependent current was observed in the presence of inhibitors of K+
      channels, Ba2+ (100 microM) or iberiotoxin (100 nM), and was not affected by
      inhibitors of nonselective cation channels, La3+, or by inhibition of the Cl
      /HCO3- transporter by bumetanide. The inhibitors of the Cl- channel, NPPB (0.1
      mM) or DIDS (100 microM), partially prevented activation of superoxide-dependent
      current but were unable to reverse it. The effects of superoxide on the amplitude
      of whole cell current were prevented and reversed by superoxide dismutase. Taken
      together, these results suggest that superoxide directly affects the function of
      ion channels in vascular endothelium but the mechanisms of its modulatory effects
      remain unresolved.

PMID- 15964928
TI  - Tetrahydrobiopterin corrects Escherichia coli endotoxin-induced endothelial
      dysfunction.
AB  - Acute inflammation causes endothelial dysfunction, which is partly mediated by
      oxidant stress and inactivation of nitric oxide. The contribution of depletion of
      tetrahydrobiopterin (BH(4)), the cofactor required for nitric oxide generation,
      is unclear. In this randomized, double-blind, three-way crossover study, forearm
      blood flow (FBF) responses to ACh and glyceryltrinitrate (GTN) were measured
      before and 3.5 h after infusion of Escherichia coli endotoxin (LPS, 20 IU/kg iv)
      in eight healthy men. The effect of intra-arterial BH(4) (500 microg/min),
      placebo, or vitamin C (24 mg/min) was studied on separate days 3.5 h after LPS
      infusion. In addition, human umbilical vein endothelial cells were incubated for
      24 h with vitamin C and LPS. ACh and GTN caused dose-dependent forearm
      vasodilation. The FBF response to ACh, which was decreased by 23 +/- 17% (P <
      0.05) by LPS infusion, was restored to baseline reactivity by BH(4) and vitamin
      C. FBF responses to GTN were not affected by BH(4) or vitamin C. LPS increased
      leukocyte count, high-sensitivity C-reactive protein, IL-6, IL-1beta, IFN-gamma,
      monocyte chemoattractant protein-1, pulse rate, and body temperature and
      decreased platelet count and vitamin C concentration. Vitamin C increased forearm
      plasma concentration of BH(4) by 32% (P < 0.02). Incubation with LPS and vitamin
      C, but not LPS alone, increased intracellular BH(4) concentration in human
      umbilical vein endothelial cells. Impaired endothelial function during acute
      inflammation can be restored by BH(4) or vitamin C. Vitamin C may exert some of
      its salutary effects by increasing BH(4) concentration.

PMID- 15964929
TI  - The influence of body size on measurements of overall cardiac function.
AB  - The purpose of this study was to determine the best scaling method to account for
      the effects of body size on measurements of overall cardiac function and
      subsequently the interpretation of data based on cardiac power output (CPO). CPO
      was measured at rest (CPO(rest)) and at maximal exercise (CPO(max)) on 88 and 103
      healthy but untrained men and women, respectively, over the age range of 20-70
      yr. Cardiac reserve (CR) was calculated as CPO(max) - CPO(rest). CPO(rest),
      CPO(max), and CR were all significantly related to body mass (BM), body surface
      area (BSA), and lean body mass (LBM). The linear regression model failed to
      completely normalize these measurements. In contrast, the allometric model
      produced size-independent values of CPO. Furthermore, all the assumptions
      associated with the allometric model were achieved. For CPO(rest), mean body size
      exponents were BM(0.33), BSA(0.60), and LBM(0.47). For CPO(max), the exponents
      were BM(0.41), BSA(0.81), and LBM(0.71). For CR, mean body size exponents were
      BM(0.44), BSA(0.87), and LBM(0.79). LBM was identified (from the root-mean
      squares errors of the separate regression models) as the best physiological
      variable (based on its high metabolic activity) to be scaled in the allometric
      model. Scaling of CPO to LBM(b) (where b is the scaling exponent) dramatically
      reduced the between-gender differences with only a 7% difference in CPO(rest) and
      CPO(max) values. In addition, the gender difference in CR was completely removed.
      To avoid erroneous interpretations and conclusions being made when comparing data
      between men and women of different ages, the allometric scaling of CPO to LBM(b)
      would seem crucial.

PMID- 15964930
TI  - Compound transfer efficiency from polystyrene surfaces: application to
      microarrayed compound screening.
AB  - In microarrayed compound screening (microARCS), compounds are spotted and dried
      onto a polystyrene sheet (ChemCard)ata high density and introduced into the assay
      by contacting with agarose gels that contain reagents for the assay. The authors
      have conducted studies to characterize the compound transfer process using 59
      compounds of diverse properties. The amount of compounds remaining on the
      ChemCard was determined by liquid chromatography/mass spectrometry after
      incubation with agarose gels for predetermined time periods. The results showed
      good correlation with kinetics of compound transfer to phosphate-buffered saline
      (PBS) buffer, but only moderate correlation with equilibrium solubility of
      compounds in PBS buffer. These observations indicate that the major factor
      determining compound transfer efficiency is the kinetics of dissolution of
      compounds, rather than equilibrium solubility and diffusion of compounds in the
      gel. Compounds of lower ClogP showed a higher rate of transfer to agarose gels
      and vice versa. Other compound properties such as molecular weight, size, acid
      base, and H-bonding properties did not significantly affect compound transfer.
      Importantly, the majority of the compounds studied show greater than 20% transfer
      after a 10-min incubation with agarose gels, providing sufficient amounts of
      compounds for screening purposes.

PMID- 15964931
TI  - Isogenic human cell lines for drug discovery: regulation of target gene
      expression by engineered zinc-finger protein transcription factors.
AB  - Isogenic cell lines differing only in the expression of the protein of interest
      provide the ideal platform for cell-based screening. However, related natural
      lines differentially expressing the therapeutic target of choice are rare. Here
      the authors report a strategy for drug screening employing isogenic human cell
      lines in which the expression of the target protein is regulated by a gene
      specific engineered zinc-finger protein (ZFP) transcription factor (TF). To
      demonstrate this approach, a ZFP TF activator of the human parathyroid hormone
      receptor 1 (PTHR1) gene was identified and introduced into HEK293 cells (negative
      for PTHR1). Following induction of ZFP TF expression, this cell line produced
      functional PTHR1 protein, resulting in a robust and ligand-specific cyclic
      adenosine monophosphate (cAMP) response. Reciprocally, the natural expression of
      PTHR1 observed in SAOS2 cells was dramatically reduced by the introduction of the
      appropriate PTHR1-specific ZFP TF repressor. Moreover, this ZFP-driven PTHR1
      repression selectively eliminated the functional cAMP response invoked by known
      ligands of PTHR1. These data establish ZFP TF-generated isogenic lines as a
      general approach for the identification of therapeutic agents specific for the
      target gene of interest.

PMID- 15964932
TI  - Two-photon excitation in fluorescence polarization receptor-ligand binding assay.
AB  - Fluorescence polarization is one of the most commonly used homogeneous assay
      principles in drug discovery for screening of potential lead compounds. In this
      article, the fluorescence polarization technique is combined with 2-photon
      excitation of fluorescence. Theoretically, the use of 2-photon excitation of
      fluorescence increases the volumetric sensitivity and polarization contrast of
      fluorescence polarization assays. The work in this report demonstrates these
      predictions for an estrogen receptor ligand binding assay.

PMID- 15964933
TI  - Screening for the optimal specificity profile of protein kinase C using
      electrospray mass-spectrometry.
AB  - A peptide library approach based on electrospray mass-spectrometric (ESI-MS)
      detection of phosphopeptides was designed for rapid and quantitative
      characterization of protein kinase specificity. The k(cat)/K(m) values for the
      protein kinase Cbeta (PKCbeta) were determined for a systematically varied set of
      individual substrate peptides in library mixtures by the ESI-MS method. The
      analysis revealed a complex structural specificity profile in positions around
      the phosphorylated serine with hydrophobic and/or basic residues being mostly
      preferred. On the basis of the kinetic parameters, a highly efficient peptide
      substrate for PKCbeta (K(m)value below 100 nM) FRRRRSFRRR and its alanine
      substituted pseudosubstrate-analog inhibitor (K(i) value of 76 nM) were designed.
      The quantitative specificity profiles obtained by the new approach contained more
      information about kinase specificity than the conventional substrate consensus
      motifs. The new method presents a promising basis for design of substrate-site
      directed peptide or peptidomimetic inhibitors of protein kinases. Second, highly
      specific substrates could be designed for novel applications such as high
      throughput protein kinase activity screens on protein kinase chips.

PMID- 15964934
TI  - Development of a microplate-based, electrophoretic fluorescent protein kinase a
      assay: comparison with filter-binding and fluorescence polarization assay
      formats.
AB  - A microplate-based electrophoretic assay has been developed for the
      serine/threonine kinase protein kinase A (PKA). The ElectroCapture PKA assay
      developed uses a positively charged, lissamine-rhodamine-labeled kemptide peptide
      substrate for the kinase reaction and Nanogen's ElectroCapture HTS Workstation
      and 384-well laminated membrane plates to electrophoretically separate the
      negatively charged phosphorylated peptide product from the kinase reaction mix.
      After the electrophoretic separation, the amount of rhodamine-labeled
      phosphopeptide product was quantified using a Tecan Ultra384 fluorescence reader.
      The ElectroCapture PKA assay was validated with both known PKA inhibitors and
      library compounds. The pK(iapp) results obtained in the ElectroCapture PKA assay
      were comparable to those generated with current radioactive filter-binding assay
      and antibody-based competitive fluorescence polarization PKA assay formats.

PMID- 15964935
TI  - Evaluation of a high-throughput fluorescence assay method for HERG potassium
      channel inhibition.
AB  - The number of projects in drug development that fail in late phases because of
      cardiac side effects such as QT prolongation can impede drug discovery and
      development of projects. The molecular target responsible for QT prolongation by
      a wide range of pharmaceutical agents is the myocardial hERG potassium channel.
      It is therefore desirable to screen for compound interactions with the hERG
      channel at an early stage of drug development. Here, the authors report a cell
      based fluorescence assay using membrane potential-sensitive fluorescent dyes and
      stably transfected hERG channels from CHO cells. The assay allows semiautomated
      screening of compounds for hERG activity on 384-well plates and is sufficiently
      rapid for testing a large number of compounds. The assay is robust as indicated
      by a Z' factor larger than 0.6. The throughput is in the range of 10,000 data
      points per day, which is significantly higher than any other method presently
      available for hERG. The data obtained with the fluorescence assay were in
      qualitative agreement with those from patch-clamp electrophysiological analysis.
      There were no false-positive hits, and the rate of false-negative compounds is
      currently 12% but might be further reduced by testing compounds at higher
      concentration. Quantitative differences between fluorescence and
      electrophysiological methods may be due to the use- or voltage-dependent activity
      of the antagonists.

PMID- 15964936
TI  - Enzyme inhibitor screening using a homogeneous proximity-based immunoassay for
      estradiol.
AB  - The authors have previously reported a homogeneous time-resolved fluorescence
      proximity immunoassay for estradiol. The assay was based on luminescence
      resonance energy transfer between a long lifetime fluorescent europium(III)
      chelate-dyed nanoparticle donor and a short lifetime, near-infrared fluorescent
      acceptor. The energy transfer prolonged the lifetime of the sensitized acceptor
      emission, and the fluorescence of the acceptor was measured using a time-resolved
      detection. The developed immunoassay was employed to screen inhibitors for enzyme
      17beta-hydroxysteroid dehydrogenase type 1. The enzyme overexpressed in MCF-7
      cells catalyzed a reversible conversion of estroneto17beta-estradiol. The
      inhibition efficiency of the tested molecule was obtained by comparing the final
      concentration of converted estradiol after 60 min of conversion reaction in a
      sample and in a conversion control not containing an inhibitor. The Zbeta factor
      calculated using the E2 concentrations of the homogeneous assay was 0.64,
      demonstrating a relatively good performance of the assay. The results from the
      homogeneous assay were comparable with the results obtained using radioactively
      labeled estrone as a substrate and high-performance liquid chromatography (HPLC)
      separation of estrone and converted estradiol after the enzyme reaction. Thus,
      this homogeneous assay can simplify the primary screening of potential new drug
      molecules by replacing a tedious radiometric HPLC method.

PMID- 15964937
TI  - Cell-based assays to detect inhibitors of fungal mRNA capping enzymes and
      characterization of sinefungin as a cap methyltransferase inhibitor.
AB  - The m7GpppN cap at the 5' end of eukaryotic mRNAs is important for transcript
      stability and translation. Three enzymatic activities that generate the mRNA cap
      include an RNA 5'-triphosphatase, an RNA guanylyltransferase, and an RNA (guanine
      7-) -methyltransferase. The physical organization of the genes encoding these
      enzymes differs between mammalian cells and yeast, fungi, or viruses. The
      catalytic mechanism used by the RNA triphosphatases of mammalian cells also
      differs from that used by the yeast, fungal, or viral enzymes. These structural
      and functional differences suggest that inhibitors of mRNA capping might be
      useful antifungal or antiviral agents. The authors describe several whole-cell
      yeast-based assays developed to identify and characterize inhibitors of fungal
      mRNA capping. They also report the identification and characterization of the
      natural product sinefungin in the assays. Their characterization of this S
      adenosylmethionine analog suggests that it inhibits mRNA cap methyltransferases
      and exhibits approximately 5- to 10-fold specificity for the yeast ABD1 and
      fungal CCM1 enzymes over the human Hcm1 enzyme expressed in yeast cells.

PMID- 15964938
TI  - Validation of a fluorescent imaging plate reader membrane potential assay for
      high-throughput screening of glycine transporter modulators.
AB  - A fluorescent imaging plate reader (FLIPR) membrane potential (V(m)) assay was
      evaluated for pharmacological characterization and high-throughput screening
      (HTS) of rat glycine transporter type 2 (rGlyT(2)) in a stable rGlyT(2)-HEK cell
      line. Data show that glycine activation of rGlyT(2) consistently results in a
      concentration-dependent V(m) response on the FLIPR that is blocked by the potent
      and selective GlyT(2) antagonist 4-benzyloxy-3,5-dimethoxy-N-[1-dimethylamino
      cyclopentyl)methyl]-benz-amide (Org-25543). Agonist and antagonist pharmacologies
      match those reported using conventional [(3)H]glycine uptake assays and
      electrophysiology. The glycine response is dependent on buffer ionic composition
      consistent with GlyT(2) physiology. Assay signal-to-background and coefficient of
      variation meets sufficient statistical criteria to conduct HTS. The results of a
      screen of the chemical inventory demonstrate that the assay is able to
      successfully identify and confirm GlyT(2) inhibitors. The advantages of this
      assay are its homogeneity, compatibility with both 96- and 384-well formats, and
      lack of radioactivity usage. Thus, the authors conclude that a fluorescence-based
      V(m) assay on FLIPR is a viable approach for identification and pharmacological
      profiling of small molecule modulators of the electrogenic transporter rGlyT(2).

PMID- 15964939
TI  - High-throughput screening with HyperCyt flow cytometry to detect small molecule
      formylpeptide receptor ligands.
AB  - High-throughput flow cytometry (HTFC), enabled by faster automated sample
      processing, represents a promising high- content approach for compound library
      screening. HyperCyt is a recently developed automated HTFC analysis system by
      which cell samples are rapidly aspirated from microplate wells and delivered to
      the flow cytometer. The formylpeptide receptor (FPR) family of G protein-coupled
      receptors contributes to the localization and activation of tissue-damaging
      leukocytes at sites of chronic inflammation. Here, the authors describe
      development and application of an HTFC screening approach to detect potential
      anti-inflammatory compounds that block ligand binding to FPR. Using a homogeneous
      no-wash assay, samples were routinely processed at 1.5 s/well (approximately 2500
      cells analyzed/sample), allowing a 96-well plate to be processed in less than 2.5
      min. Assay sensitivity and accuracy were validated by detection of a previously
      documented active compound with relatively low FPR affinity (sulfinpyrazone,
      inhibition constant [K(i)]=14 microM) from among a collection of 880 compounds in
      the Prestwick Chemical Library. The HyperCyt system was therefore demonstrated to
      be a robust, sensitive, and highly quantitative method with which to screen lead
      compound libraries in a 96-well format.

PMID- 15964940
TI  - Linking solubility and permeability assays for maximum throughput and
      reproducibility.
AB  - Solubility and permeability are intimately linked in drug absorption processes.
      They have, however, been traditionally assayed separately. To support this
      linkage, a combined solubility/permeability assay was developed for determining
      absorption properties of chemical entities. First, solubility is determined at 4
      pH values by comparing the concentration of a saturated compound solution to its
      dilute, known concentration. The filtered, saturated solution from the solubility
      assay is then used as input material for the membrane permeability determination.
      The permeability assay is a parallel artificial membrane technique whereby a
      membrane is created on a solid support parallel artificial membrane permeation
      assay (PAMPA). The 2 artificial membranes presented here model the
      gastrointestinal tract and the blood-brain barrier (BBB). Data are presented for
      control compounds, which are well documented in the literature and exemplify a
      range of solubility and membrane permeability. The advantages of the combination
      method are 1) reduction of sample usage and preparation time, 2) elimination of
      interference from compound precipitation in membrane permeability determination,
      3) maximization of input concentration to permeability assay for improved
      reproducibility, and 4) optimization of sample tracking by streamlining data
      entry and calculations. BBB permeability ranking of compounds correlates well
      with literature CNS activity.

PMID- 15964941
TI  - Treatment of bifurcation lesions with two stents: one year angiographic and
      clinical follow up of crush versus T stenting.
AB  - OBJECTIVES: To compare long term outcomes of the crush versus the T technique in
      bifurcation lesions. DESIGN: 182 consecutive patients were identified who
      underwent percutaneous coronary interventions for bifurcation lesions with drug
      eluting stents between April 2002 and January 2004. Two techniques were used
      according to the operator's discretion: crush (group C, n = 121) or T (group T, n
      = 61). RESULTS: In-hospital outcome differed significantly between the two
      groups. Angiographic follow up was available for 142 (78%) patients. Groups C and
      T did not differ significantly regarding late loss (0.42 (0.39) mm v 0.34 (0.35)
      mm, p = 0.52) and rate of restenosis (16.2% v 13.0%, p = 0.80) in both the main
      and the side branch without final kissing balloon post-dilatation. However, when
      final kissing balloon post-dilatation was performed, group C had significantly
      lower late lumen loss (0.23 (0.21) mm v 0.37 (0.33) mm, p = 0.02) and restenosis
      rate (8.6% v 26.5%, p = 0.04) in the side branch. At one year's clinical follow
      up, group C compared with group T had lower rates of target lesion
      revascularisation (14.0% v 31.1%, p = 0.01) and target vessel revascularisation
      (16.5% v 32.8%, p = 0.02). CONCLUSIONS: In non-selected bifurcation lesions
      treated with drug eluting stents, the restenosis rate remains relatively high in
      the side branch. Compared with the T stenting technique, crush stenting with
      kissing balloon post-dilatation is associated with a reduced rate of restenosis
      in the side branch.

PMID- 15964942
TI  - Coronary artery remodelling is related to plaque composition.
AB  - OBJECTIVE: To assess the potential relation between plaque composition and
      vascular remodelling by using spectral analysis of intravascular ultrasound
      (IVUS) radiofrequency data. METHODS AND RESULTS: 41 coronary vessels with non
      significant (< 50% diameter stenosis by angiography), < or = 20 mm, non-ostial
      lesions located in non-culprit vessels underwent IVUS interrogation. IVUS
      radiofrequency data obtained with a 30 MHz catheter, were analysed with IVUS
      virtual histology software. A remodelling index (RI) was calculated and divided
      into three groups. Lesions with RI > or = 1.05 were considered to have positive
      remodelling and lesions with RI < or = 0.95 were considered to have negative
      remodelling. Lesions with RI > or = 1.05 had a significantly larger lipid core
      than lesions with RI 0.96-1.04 and RI < or = 0.95 (22.1 (6.3) v 15.1 (7.6) v 6.6
      (6.9), p < 0.0001). A positive correlation between lipid core and RI (r = 0.83, p
      < 0.0001) and an inverse correlation between fibrous tissue and RI (r = -0.45, p
      = 0.003) were also significant. All of the positively remodelled lesions were
      thin cap fibroatheroma or fibroatheromatous lesions, whereas negatively
      remodelled lesions had a more stable phenotype, with 64% having pathological
      intimal thickening, 29% being fibrocalcific lesions, and only 7%
      fibroatheromatous lesions (p < 0.0001). CONCLUSIONS: In this study, in vivo
      plaque composition and morphology assessed by spectral analysis of IVUS
      radiofrequency data were related to coronary artery remodelling.

PMID- 15964943
TI  - Compliance with and effectiveness of adaptive servoventilation versus continuous
      positive airway pressure in the treatment of Cheyne-Stokes respiration in heart
      failure over a six month period.
AB  - OBJECTIVE: To compare compliance with and effectiveness of adaptive
      servoventilation (ASV) versus continuous positive airway pressure (CPAP) in
      patients with the central sleep apnoea syndrome (CSA) with Cheyne-Stokes
      respiration (CSR) and with congestive heart failure in terms of the apnoea
      hypopnoea index (AHI), quality of life, and left ventricular ejection fraction
      (LVEF) over six months. METHODS: 25 patients (age 28-80 years, New York Heart
      Association (NYHA) class II-IV) with stable congestive heart failure and CSA-CSR
      were randomly assigned to either CPAP or ASV. At inclusion, both groups were
      comparable for NYHA class, LVEF, medical treatment, body mass index, and CSA-CSR.
      RESULTS: Both ASV and CPAP decreased the AHI but, noticeably, only ASV completely
      corrected CSA-CSR, with AHI below 10/h. At three months, compliance was
      comparable between ASV and CPAP; however, at six months compliance with CPAP was
      significantly less than with ASV. At six months, the improvement in quality of
      life was higher with ASV and only ASV induced a significant increase in LVEF.
      CONCLUSION: These results suggest that patients with CSA-CSR may receive greater
      benefit from treatment with ASV than with CPAP.

PMID- 15964944
TI  - Remote sensing of malaria in urban areas: two scales, two problems.

PMID- 15964946
TI  - Dynamic determinants of the cytoadherence of Plasmodium falciparum-infected
      erythrocytes.

PMID- 15964947
TI  - Attenuation of cytoadherence of Plasmodium falciparum to microvascular
      endothelium under flow by hemodilution.
AB  - The cytoadherence of Plasmodium falciparum-infected erythrocytes (IRBCs) to
      endothelium is mediated by adhesion molecules within the physical constraints of
      a viscous fluid containing mostly erythrocytes. The volume fraction of
      erythrocytes (hematocrit) and their physical properties, such as deformability,
      are important properties of blood that affect cell recruitment to the vascular
      wall. In the present study, we examined the effect of hematocrit on IRBC rolling
      and adhesion on human microvascular endothelial cells in a flow chamber system in
      vitro. We found hematocrit to be a major determinant of IRBC/endothelial cell
      interactions. There was a 5-fold and 12-fold increase in IRBC rolling and
      adhesion, respectively, when hematocrit increased from 10% to 30%, as a result of
      changes in shear rate. Similar effects were seen in the presence of less
      deformable erythrocytes, serum proteins, and on endothelium stimulated with tumor
      necrosis factor-alpha. The results indicate that hemorheologic variations are an
      important determinant of the degree of cytoadherence.

PMID- 15964948
TI  - Dramatic difference in diversity between Plasmodium falciparum and Plasmodium
      vivax reticulocyte binding-like genes.
AB  - Malaria parasite proteins involved in erythrocyte invasion are considered
      important vaccine targets. Members of the reticulocyte binding-like (RBL) family
      of Plasmodium merozoite proteins are found in human, simian, and rodent malaria
      parasites and function in the initial steps of erythrocyte selection and
      invasion. The RBL genes are large, ranging in size from 7.7 to 10 kb, and the
      extent of any sequence diversity in parasite populations is unknown. We present
      the first assessment of sequence diversity within RBL genes from the two major
      human malaria parasites: Plasmodium falciparum and P. vivax. Polymorphism within
      the RBL genes is generally limited, except for P. vivax reticulocyte binding
      protein 2 (PvRBP2), which has nucleotide diversity levels 25-fold higher than the
      other RBL genes. The PvRBP2 haplotypes appear to fall into two distinct classes
      of alleles, suggesting large-scale dimorphism in this gene. Polymorphisms were
      frequently clustered, suggesting that different RBL domains may be evolving under
      different selection and functional pressures.

PMID- 15964949
TI  - Anti-Plasmodium vivax duffy binding protein antibodies measure exposure to
      malaria in the Brazilian Amazon.
AB  - Plasmodium vivax Duffy binding protein (DBP) is functionally important in the
      erythrocyte invasion process and provides a logical target for vaccine-mediated
      immunity. In the current study, we demonstrated that DBP is naturally immunogenic
      in different populations of the Brazilian Amazon, and the proportions of DBP IgG
      positive subjects increased with exposure to malaria, reaching a peak in those
      subjects with long-term exposure (> 15 years) in the Amazon area. This profile of
      antibody response was significantly different from the one observed for the P.
      vivax merozoite surface protein 1 (MSP1(19)), which was relatively uniform in
      areas with markedly different levels of malaria transmission. In a small sample
      of adults with symptomless P. vivax infection, we could not detect any
      significant correlation between antibodies against these P. vivax proteins and
      asymptomatic infection. Our study provided an additional insight by demonstrating
      cumulative exposure as a determinant that acts independently of host age in
      generation of anti-DBP IgG response.

PMID- 15964950
TI  - Malaria prevalence and associated risk factors in Eritrea.
AB  - A parasitological cross-sectional survey was undertaken from September 2000
      through February 2001 to estimate the prevalence of malaria parasitemia in
      Eritrea. A total of 12,937 individuals from 176 villages were screened for both
      Plasmodium falciparum and Plasmodium vivax parasite species using the OptiMal
      Rapid Diagnostic Test. Malaria prevalence was generally low but highly focal and
      variable with the proportion of parasitemia at 2.2% (range: 0.4% to 6.5%).
      Despite no significant differences in age or sex-specific prevalence rates, 7% of
      households accounted for the positive cases and 90% of these were P. falciparum.
      Multivariate regression analyses revealed that mud walls were positively
      associated with malaria infection (OR [odds ratio] = 1.6 [95% CI: 1.2, 2.2], P <
      0.008). For countries with low and seasonal malaria transmission, such
      information can help programs design improved strategic interventions.

PMID- 15964951
TI  - Rapid malaria screening and targeted treatment of United States-bound Montagnard
      refugees from Cambodia in 2002.
AB  - In 2002, a group of Montagnard refugees living in Cambodia was accepted for
      resettlement in the United States. Pre-departure malaria screening and targeted
      treatment was conducted to prevent morbidity, and minimize the potential for
      local malaria transmission post-arrival. We screened 902 of 906 refugees using
      rapid diagnostic tests (RDTs), microscopy, and polymerase chain reaction (PCR)
      analysis. Twelve (1.3%) RDT results were positive and 28 (3.1%) were
      indeterminate. Microscopy confirmed Plasmodium species in two of the positive RDT
      and one of the indeterminate results. Among a random 10% sample of negative RDT
      results (n = 86), none were positive by microscopy. The PCR confirmed the two
      microscopically (and RDT) positive specimens. The PCR result was negative for all
      other specimens tested. Eighteen (2.0%) refugees were treated with antimalarials.
      The RDTs were useful in this setting, facilitating timely, sensitive diagnosis
      and targeted treatment. Evaluations to determine the most appropriate
      interventions in other refugee settings should include cost-effectiveness
      analyses of alternative strategies.

PMID- 15964952
TI  - Measuring allelic heterogeneity in Plasmodium falciparum by a heteroduplex
      tracking assay.
AB  - We developed a novel Plasmodium falciparum genotyping strategy based on the
      heteroduplex tracking assay (HTA) method commonly used to genotype viruses.
      Because it can detect both sequence and size polymorphisms, we hypothesized that
      HTA is more sensitive than current methods. To test this hypothesis, we compared
      the ability of HTA and a nested polymerase chain reaction (PCR) to detect genetic
      diversity in 17 Thai samples. The HTA detected more MSP1 sequence variants in
      eight isolates (47%), less sequence variants in three isolates (18%), and an
      equal number of sequence variants in six isolates (35%), suggesting that HTA is
      equal to or more sensitive than the nested PCR. This study is a proof of concept
      that HTA is a sensitive allelic discrimination method able to determine genetic
      diversity in P. falciparum and warrants its use in studies of antimalarial drug
      efficacy.

PMID- 15964953
TI  - Coinfection with Plasmodium falciparum and schistosoma haematobium: protective
      effect of schistosomiasis on malaria in senegalese children?
AB  - Studies with animal models have suggested the possibility of interactions between
      parasites during concurrent infections and have raised the question of a similar
      phenomenon in humans. The present survey was undertaken to assess the impact of
      urinary schistosomiasis on the susceptibility of children to malaria. It was
      carried out in Senegal between September 2001 and March 2002 among 523 children 3
      15 years of age. We tested the association between Plasmodium falciparum
      densities and the load of Schistosoma haematobium egg excretion using a linear
      mixed model because data were not independent. After controlling for age, sex,
      and season, we showed that children lightly infected with S. haematobium (1-9
      eggs/10 mL of urine) had lower P. falciparum densities than those not infected
      (beta = -0.34, 95% confidence interval = -0.85, -0.10), suggesting a negative
      interaction between both parasites.

PMID- 15964955
TI  - Characterization of a human reference standard for antibody to Plasmodium
      falciparum merozoite surface protein 1(42).
AB  - Volunteers vaccinated with a candidate malaria vaccine containing merozoite
      surface protein 1(42) (MSP-1(42)) exhibit antibodies to MSP-1(42) that are
      measured by enzyme-linked immunosorbent assay (ELISA). The purpose of this study
      was to make a human reference standard for MSP-1(42) antibody measured in
      absolute quantity units using pooled plasma samples known to contain high titers
      of MSP-1(42) antibody based on previous ELISA results. Immobilized metal affinity
      chromatography was used to determine the amount of MSP-1(42) antibody in this
      plasma pool. Hexahistidine-tagged MSP-1(42) antigen adsorbed to nickel-chelating
      resin was used to capture MSP-1(42) antibody from the plasma pool. The intact MSP
      1(42) antibody-antigen complexes were eluted and total IgG was measured by an
      ELISA standardized against purified human IgG. In this way, the human reference
      standard was determined to contain 48.3 microg/mL of MSP-1(42) antibody. This
      reference standard may be useful as a quantitative working standard for measuring
      MSP-1(42) antibody response in future vaccine clinical trials involving MSP-1.

PMID- 15964954
TI  - Antibody reactivity to linear epitopes of Plasmodium falciparum cytoadherence
      linked asexual gene 9 in asymptomatic children and adults from papua new Guinea.
AB  - The cytoadherence-linked asexual gene 9 (clag 9) of Plasmodium falciparum has
      been implicated in the cytoadherence of infected erythrocytes. To determine the
      immunogenicity of the clag 9 gene product (CLAG 9 protein) in humans, we measured
      antibody responses to 11 synthetic CLAG 9 peptides in a group of 177 asymptomatic
      children and adults subject to intense malaria exposure in Madang, Papua New
      Guinea. The CLAG 9 peptides were immunogenic in adults and children. Antibody
      responses to peptides 4 and 10 were high across all age groups and detectable in
      a majority of children less than five years of age. While CLAG 9 peptides are
      immunogenic in humans, longitudinal studies will be required to determine the
      longevity of antibody responses to CLAG 9 and their role in protection from
      disease.

PMID- 15964956
TI  - Large sequence heterogeneity of the small subunit ribosomal RNA gene of
      Plasmodium ovale in cambodia.
AB  - Plasmodium ovale malaria has been reported in various countries in southeast
      Asia, but never in Cambodia. Using a species-specific polymerase chain reaction
      (PCR) targeting the small subunit (SSU) ribosomal RNA (rRNA) gene, we detected P.
      ovale in nearly 4% of the inhabitants of a northeastern Cambodian village.
      Plasmodium ovale was associated with at least one other Plasmodium species, and
      two quadruple infections were detected. The diagnosis was confirmed by microscopy
      and by SSU rRNA PCR product sequencing. The sequences shared 96-99% identity with
      published sequences, and displayed a substantial heterogeneity with 2-4 different
      haplotypes per sample. Nine distinct SSU rRNA haplotypes were identified,
      including seven novel variants. Phylogenetic analysis showed two major genetic
      clusters, suggesting amplification of two distinct gene sets and/or P. ovale
      variants from each sample. Our data indicate that P. ovale was overlooked in
      Cambodia until now, and call for the implementation of larger prevalence surveys
      and accurate diagnosis methods in this country.

PMID- 15964957
TI  - Vector abundance and malaria transmission in rice-growing villages in Mali.
AB  - Anophelism without malaria has long been recognized. In large irrigation
      projects, such as that around Niono, Mali, villages in irrigated areas sometimes
      have more anopheline vectors of malaria than adjacent nonirrigated villages, but
      overall malaria prevalence is substantially less. One hypothesized explanation
      for this is high anopheline densities lead to smaller adults, who do not live so
      long and hence are less efficient at transmitting the disease. We analyzed serial
      collections from 18 villages in an irrigated area of Mali, measuring correlations
      between mosquito densities and survival rates, zoophilic rates, and vectorial
      capacity over the villages and times. Adult density was inversely related to
      anthropophily and adult survival and its relationship with vectorial capacity was
      positive at low mosquito densities, flat at intermediate densities, and negative
      at high densities. This may partly explain why malaria prevalence is low in
      irrigated villages with high Anopheles density.

PMID- 15964958
TI  - Recombinant larvicidal bacteria with markedly improved efficacy against culex
      vectors of west nile virus.
AB  - An urgent need exists for new agents to control mosquito vectors of disease.
      Mosquito larvicides based on the bacteria Bacillus thuringiensis subsp.
      israelensis (Bti) or B. sphaericus (Bs) are effective in many habitats, but use
      is limited by their high cost. Moreover, mosquito resistance evolves rapidly to
      Bs where it is used intensively. The efficacy of these bacteria is due to a
      binary protein (BsB) in Bs and four proteins (Cry4A, Cry4B, Cry11A, and Cyt1A) in
      Bti. Here we report the use of cyt1A promoters and a 5' mRNA stabilizing sequence
      to synthesize high levels of Bs2362 binary toxin in Bti strains. The recombinant
      BtiIPS-82/BsB showed high potency against fourth instars of Culex
      quinquefasciatus, a vector of West Nile virus, being 21-fold as potent as BtiIPS
      82, and 32-fold as potent as Bs2362. Similar improved efficacy was obtained
      against larvae of Cx. tarsalis. Moreover, BtiIPS-82/BsB suppressed resistance to
      Bs2362 in Cx. quinquefasciatus.

PMID- 15964959
TI  - Combination of a non-pyrethroid insecticide and a repellent: a new approach for
      controlling knockdown-resistant mosquitoes.
AB  - Although pyrethroid-treated materials are a promising tool for the prevention and
      the control of dengue in the tropics, the development of pyrethroid resistance in
      the main mosquito vector (Aedes aegypti) may negate their use for personal and/or
      community protection. In that context, the efficacy of a mixture of a repellent
      (N,N-diethyl toluamide [DEET]) and a non-pyrethroid insecticide (propoxur) was
      investigated under laboratory conditions against both pyrethroid-susceptible and
      pyrethroid-resistant mosquitoes with the knockdown resistance (kdr) mutation. The
      results showed that a combination of propoxur and DEET induced a knockdown effect
      and mortality as high as deltamethrin (a standard pyrethroid) against the
      susceptible strain, and significantly higher efficacy against the pyrethroid
      resistant strain. This could be explained mainly by the existence of a strong
      synergistic interaction between DEET and propoxur in mosquitoes. This study
      constitutes a first step towards an alternative strategy for improving mosquito
      control in areas with pyrethroid resistance.

PMID- 15964960
TI  - Estimating and modeling the dynamics of the intensity of infection with
      schistosoma japonicum in villagers of leyte, Philippines. Part II: Intensity
      specific transmission of S. japonicum. The schistosomiasis transmission and
      ecology project.
AB  - A dynamic model of Schistosoma japonicum transmission is presented that
      incorporates effects of infection intensity, age, and sex. We use four infection
      intensity classes to investigate the impact of ecologic changes and public health
      interventions on the burden of infection within communities. Age- and sex
      specific infection data from three disease-endemic villages in the Philippines
      are used to estimate the parameters of the model. The model gives good
      qualitative agreement with observed fecal egg counts adjusted for the accuracy of
      the Kato-Katz examination. Our results suggest that differences in infection
      burden between villages are caused by differences in both the infection process
      and the recovery process in humans. We describe the potential impact of mass
      treatment of all humans on the numbers with high infection. Furthermore, we show
      that a sudden reduction in snail population size would affect high prevalence and
      low prevalence communities in different ways.

PMID- 15964961
TI  - Risk factors associated with hepatitis C among patients co-infected with human
      immunodeficiency virus: a case-control study.
AB  - A case-control study was carried out to assess the risk factors associated with
      hepatitis C in patients infected with human immunodeficiency virus. One hundred
      eighteen patients tested positive for hepatitis C virus (HCV) and were included
      as cases, and 117 tested negative for HCV and were included as controls.
      Information was collected through a questionnaire. The risk factors that showed a
      significant association with co-infection by multivariate analysis were an age of
      30-39 years (odds ratio [OR] = 4.65, 95% confidence interval [CI] = 1.31-16.43),
      an age of 40-49 years (OR = 6.48, 95% CI = 1.70-24.78), an age > 50 years (OR =
      7.50, 95% CI = 1.54-36.68), use of intravenous drugs (OR = 25.46, 95% CI = 4.91
      131.88), use of inhaled illicit drugs (OR = 3.56, 95% CI = 1.22-10.44), anal
      intercourse (OR = 3.93, 95% CI = 1.27-12.13), a sexual partner with a history of
      liver disease (OR = 5.45, 95% CI = 1.33-22.32), a sexual partner with a history
      of blood transfusions (OR = 4.79, 95% CI = 0.95-24.19), and sexual partner with a
      history of intravenous drug use (OR = 3.46, 95% CI = 1.24-9.65).

PMID- 15964962
TI  - The emergence of west nile virus during a large outbreak in Illinois in 2002.
AB  - In 2002, the world's largest outbreak of neuroinvasive West Nile virus (WNV)
      disease occurred. Illinois reported 21% of the total cases in the United States,
      the most among all states. The epidemiology of WNV in Illinois in 2002 was
      examined to determine factors associated with severe disease and death. A total
      of 884 cases were identified and there were 66 deaths. The overall attack rate of
      WNV infection was 7.1 per 100,000 population and this increased with age. The
      median ages of patients and patients who died were 56 and 78 years, respectively.
      Among patients who died, 91% were diagnosed with encephalitis and the case
      fatality rate for patients with encephalitis was 18.6%. Patients more than 50
      years old had a significantly higher risk of being reported with encephalitis
      (relative risk [RR] = 3.3, 95% confidence interval [CI] = 2.6-4.3%) and death (RR
      = 22.3, 95% CI = 5.5-90.4%). Clinicians evaluating elderly patients with WNV
      infection should assess patients closely for progression of disease.

PMID- 15964963
TI  - Th(2) immune response in patients with dengue during defervescence: preliminary
      evidence.
AB  - A shift from a T(H)1 to a T(H)2 immune response has been observed in vitro during
      dengue virus infection. Estimation of plasma IgE level (n = 28), CD4:CD8
      lymphocyte ratio, and the intracellular interferon-gamma (IFN-gamma):interleukin
      4 (IL-4) ratio (n = 9) was conducted in patients with various severities of
      dengue around the time of defervescence. The CD4:CD8 lymphocyte ratio was
      significantly lower (median = 0.45, interquartile range [IQR] = 0.4-0.47 versus
      1.3, 1.0-1.9; P = 0.001), and IgE levels were significantly higher (mean = 300.4,
      SD = 252.5 versus 143.7, 117.9 IU/mL; P = 0.004) in patients than in healthy
      controls. The intracellular IFN-gamma:IL-4 ratio was significantly lower in
      patients compared with controls (0.28, 0.13 versus 0.99, 0.4; P = 0.001). These
      findings suggest that a T(H)2 immune response occurs in patients with dengue
      around the time of defervescence.

PMID- 15964964
TI  - Economic impact of dengue fever/dengue hemorrhagic fever in Thailand at the
      family and population levels.
AB  - Dengue fever and dengue hemorrhagic fever constitute a substantial health burden
      on the population in Thailand. In this study, the impact of symptomatic dengue
      virus infection on the families of patients hospitalized at the Kamphaeng Phet
      Provincial Hospital with laboratory-confirmed dengue in 2001 was assessed, and
      the disability-adjusted life years (DALYs) lost for fatal and non-fatal cases of
      dengue were calculated using population level data for Thailand. When we
      accounted for the direct cost of hospitalization, indirect costs due to loss of
      productivity, and the average number of persons infected per family, we observed
      a financial loss of approximately US$61 per family, which is more than the
      average monthly income in Thailand. The DALYs were calculated using select
      results from a family level survey, and resulted in an estimated 427
      DALYs/million population in 2001. This figure is of the same order of magnitude
      as the impact of several diseases currently given priority in southeast Asia,
      such as the tropical cluster (trypanosomiasis, Chagas disease, schistosomiasis,
      leishmaniasis, lymphatic filariasis, and onchocerciasis), malaria, meningitis,
      and hepatitis. These results indicate that dengue prevention, control, and
      research should be considered equally important as that of diseases currently
      given priority.

PMID- 15964965
TI  - Environmental predictors of Ross River virus disease outbreaks in Queensland,
      Australia.
AB  - Ross River virus (RRV) disease is the most common mosquito-borne disease in
      Australia, with the majority of cases reported from Queensland. In this study we
      investigate the relationship between local RRV disease outbreaks and standardized
      rainfall and temperature data in Queensland. No one set of variables could be
      found to accurately predict RRV disease outbreaks across all of Queensland,
      although good predictive models could be developed for smaller regions. The
      variables identified as important in predicting RRV disease outbreaks differed
      between regions, and also between summer and autumn. This work highlights the
      sensitive relationship between virus prevalence, mosquito bionomics, and climate,
      illustrating that critical climatic factors differ depending on underlying
      environmental conditions. Identification of factors leading to RRV disease
      outbreaks will help local authorities identify periods of high risk, optimizing
      the provision of additional mosquito control measures.

PMID- 15964966
TI  - Clinical survey of hantavirus in southern Brazil and the development of specific
      molecular diagnosis tools.
AB  - Hantavirus pulmonary syndrome (HPS) is an emerging disease caused by an
      increasing number of distinct hantavirus serotypes found worldwide. It is also a
      very severe immune disease. It progresses quickly and is associated with a high
      mortality rate. At the prodrome phase, hantavirosis symptoms can resemble those
      of other infectious diseases such as leptospirosis and influenza. Thus, prognosis
      could be improved by developing a rapid and sensitive diagnostic test for
      hantavirus infection, and by improving knowledge about clinical aspects of this
      disease. This study describes clinical features and laboratory parameters
      throughout the course of HPS in 98 patients. We report the seasonality and
      regional distribution of this disease in Parana State, Brazil during the last
      seven years. In addition, we evaluated a specific molecular diagnostic test based
      on a nested reverse transcriptase-polymerase chain reaction for the detection of
      hantaviruses circulating in Brazil.

PMID- 15964967
TI  - A novel, rapid assay for detection and differentiation of serotype-specific
      antibodies to Venezuelan equine encephalitis complex alphaviruses.
AB  - An epitope-blocking enzyme-linked immunosorbent assay was developed for the rapid
      differentiation of serologic responses to enzootic variety IE and ID versus
      epizootic variety IAB and IC strains of Venezuelan equine encephalitis (VEE)
      virus. Two monoclonal antibodies that differentially recognize epizootic versus
      enzootic VEE virus epitopes were used to measure the serotype-specific blocking
      abilities of antibodies in sera of naturally infected humans, equines, and
      bovines, as well as in experimentally infected equines. The assay is simple,
      species-independent, rapid, and sensitive, and will improve surveillance for VEE
      emergence. It could also be used to determine the epidemic potential of a VEE
      virus following an intentional introduction for bioterrorism.

PMID- 15964968
TI  - Sensitivity of bone marrow aspirates in the diagnosis of visceral leishmaniasis.
AB  - Bone marrow aspirates are believed to provide a safer but less sensitive method
      in the diagnosis of visceral leishmaniasis (VL) compared with splenic aspirates.
      We examined the effect of the number of fields and the time of observation on
      bone marrow smear sensitivity and compared it to our experience with spleen
      aspiration. Bone marrow smears of 98 patients and splenic aspirates from 120
      patients were examined. Among 87 patients with VL, the sensitivity of bone marrow
      aspirates was 40.2%, 65.5%, 89.7%, 92%, and 95.4% at 1, 5, 20, 30, and 60
      minutes, respectively. The sensitivity of spleen aspirate examination was 93% for
      114 patients. One patient died of shock after spleen aspiration. A bone marrow
      smear is very sensitive if examined thoroughly, reaching a sensitivity similar to
      that of spleen aspirate. We propose that a bone marrow smear be established as
      the technique of choice for the parasitologic diagnosis of VL.

PMID- 15964969
TI  - Longitudinal study of dogs living in an area of Spain highly endemic for
      leishmaniasis by serologic analysis and the leishmanin skin test.
AB  - The literature contains few longitudinal studies that have assessed areas endemic
      for canine leishmaniasis and over the same time interval Leishmania-specific
      cellular and humoral immunity in healthy dogs. Fourteen dogs, three mixed breed
      and 11 Ibizian hounds, living in an area of Spain that was highly endemic for
      leishmaniasis were followed-up over a three-year period by serologic analysis and
      the leishmanin skin test (LST). All but one of these dogs remained clinically
      healthy during the study period. Seroconversion was observed in four dogs. The
      three mixed breed dogs had a negative reaction in the LST in the first and third
      years. The general trend in the Ibizian hounds was an increase in the diameter of
      the LST reaction at both the 48- and 72-hour readings in the third year. This
      study demonstrates that in addition to an increase in Leishmania-specific humoral
      immune response in Ibizian hounds, a parallel increase in cellular immune
      response was observed.

PMID- 15964970
TI  - Localized cutaneous leishmaniasis due to Leishmania donovani and Leishmania
      tropica: preliminary findings of the study of 161 new cases from a new endemic
      focus in himachal pradesh, India.
AB  - Localized cutaneous leishmaniasis (LCL) in India is due mostly to Leishmania
      tropica. It is mainly endemic in the deserts of Rajasthan. Recently, Himachal
      Pradesh has been identified as a new endemic focus for the disease. In the last
      few years, the number of new cases has been increasing almost to epidemic
      proportions. This report presents the preliminary findings of clinico
      epidemiologic and investigative results of 161 new localized cases of LCL seen
      between May 2001 and December 2003. The study populaton was composed of 80 males
      and 81 females between 10 months and 75 years of age. All were indigenous to the
      sub-alpine valley along the Satluj River in the mountainous region of the Kinnaur
      District (altitude = 700-2,900 meters). Most patients were seen from April to
      September and had 1-8 lesions (duration = 1-6 months) that involved mainly the
      face. Tissue smears were positive for amastigotes in 37% and histopathology
      showed non-caseating epitheloid cell granuloma in 77% of the cases. Analysis by
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of
      the ribosomal gene region of 10 biopsy specimens showed amplicons
      indistinguishable from L. donovani in eight cases and L. tropica in two cases.
      Leishmania was cultured on modified Nicole-Novy-McNeal (NNN) medium containing
      RPMI 1640 medium and heat-inactivated fetal bovine serum from 13 of 38 biopsy
      samples. Three of these isolated strains were identified as L. donovani while a
      fourth was L. tropica by PCR-RFLP of the ribosomal internal transcribed spacer
      region. One strain had a gp63 sequence identical to that of east African strains.
      Another strain had a unique gp63 sequence that has not been found in L. donovani
      complex strains. Sand flies trapped in the cattle sheds of a few patients were
      identified as Phlebotomus longiductus (Parrot 1928). Treatment with intralesional
      sodium stibogluconate was effective in all patients without any major side
      effects. One patient developed lupoid leishmaniasis that responded to higher dose
      of sodium stibogluconate. Though rarely reported as a cause of LCL, L. donovani
      seems to be the predominant pathogen in this new focus of cutaneous
      leishmaniasis. Phlebotomus longiductus is a possible vector, albeit based on
      circumstantial evidence.

PMID- 15964971
TI  - Imported giardiasis: impact of international travel, immigration, and adoption.
AB  - From the Swedish national database, regarding notified Giardia cases, we could
      for the period 1997-2003 identify 3,697 cases of travel-associated giardiasis,
      4,151 cases in newly arrived immigrants and refugees, and 455 cases in
      internationally adopted children. These were compared with data sets on the
      number of international travelers, immigrants/refugees, and adopted children. The
      overall risk of being notified with giardiasis in returning travelers was 5.3 of
      100,000, with the highest incidences in travelers from the Indian Subcontinent
      (628 of 100,000), East Africa (358 of 100,000), and West Africa (169 of 100,000).
      A large proportion of the travel-related cases were seen in persons with family
      roots in the country of infection-a risk group deserving special attention. The
      overall risk in immigrants and refugees was 1,180/100,000 with the highest risk
      in persons from Afghanistan (3,800 of 100,000) and Iraq (2,990 of 100,000). The
      incidence was highest among internationally adopted children (8,110 of 100,000),
      with geographical risks not entirely correlating to those in travelers and
      immigrants.

PMID- 15964972
TI  - Protease secreted by the infective larvae of angiostrongylus cantonensis and its
      role in the penetration of mouse intestine.
AB  - The infective third-stage larvae of Angiostrongylus cantonensis secrete a
      proteolytic enzyme that is thought to be essential for both larval penetration
      into the intestinal wall of the host and full development. Protease activity in
      these larvae during culture in vitro was determined by zymography, pH optimum,
      and substrate and inhibitor specificity. Excretory-secretory (ES) products of the
      third-stage larvae showed protease activity as three bands with molecular masses
      of 66, 30, and 23 kD by gelatin zymography. The optimal pH value for this
      protease activity was 10.0. The protease was found to have collagenolytic as well
      as elastinolytic activity, but these activities were inhibited by serine protease
      or metalloprotease inhibitors. The importance of this protease in larval
      penetration of the intestinal wall and entering the blood stream was observed in
      vitro by cocultured third-stage larvae of A. cantonensis with specific protease
      inhibitors in the intestines of BALB/c mice. The penetration rates of larvae
      significantly decreased when serine protease or metalloprotease inhibitors were
      added to the intestines. These results showed that serine protease and
      metalloprotease in ES products of A. cantonensis third-stage larvae are
      associated with larval penetration of the intestinal walls of mice.

PMID- 15964973
TI  - Vaccination of pigs to control human neurocysticercosis.
AB  - Taenia solium taeniasis/cysticercosis is a zoonotic disease complex in which the
      pig is an obligate intermediate host. The infection is widespread, particularly
      in the developing world, and neurocysticercosis is a major cause of human
      neurologic disease where the parasite is endemic. Despite easy availability,
      effective anti-parasitic drugs have not been deployed effectively to control
      disease transmission. We have investigated a vaccine strategy to prevent parasite
      infection of the pig intermediate host. Such a strategy would interrupt the
      parasite's life cycle and eliminate the source of infection for humans. Two
      recombinant antigens selected from the parasite oncosphere life cycle stage were
      tested in vaccination trials in pigs that were challenged orally with Taenia
      solium eggs. Both antigens were highly effective in protecting the pigs against
      infection with the parasite (98.6% and 99.9% protection, respectively). No viable
      cysts were found in eight pigs vaccinated with one of the antigens. A recombinant
      subunit vaccine based on oncosphere antigens has the potential to improve the
      available control measures for T. solium and thereby reduce or eliminate
      neurocysticercosis.

PMID- 15964974
TI  - Spatial analysis of the distribution of Ehrlichia chaffeensis, causative agent of
      human monocytotropic ehrlichiosis, across a multi-state region.
AB  - Ehrlichia chaffeensis, which causes human monocytotrophic ehrlichiosis (HME), is
      an important emerging tick-borne pathogen in the southeastern and southcentral
      United States. The endemnicity probability of E. chaffeensis and, by implication,
      locations with risk for HME, was predicted by using two modeling methods. This is
      first large-scale study to use geospatial analyses to estimate the distribution
      of E. chaffeensis, and it was conducted using data from a prototypic surveillance
      system that used white-tailed deer as natural sentinels. Analyses included the E.
      chaffeensis serostatus for 563 counties from 18 states. Both kriging and logistic
      regression models provided very reliable portrayals of E. chaffeensis occurrence
      and predicted that E. chaffeensis distribution had good concordance with human
      case data. The integration of a deer surveillance system with geospatial analyses
      was useful in developing HME risk maps that will be useful for identifying high
      risk areas for public health interventions such as prevention and control
      efforts.

PMID- 15964975
TI  - Surveillance for antimicrobial resistance profiles among Shigella species
      isolated from a semirural community in the northern administrative area of
      santiago, chile.
AB  - Variations in antibiotic resistance patterns were studied among 178 Shigella
      strains isolated from 1997 to 2001 in children less than five years of age with
      acute diarrhea from Colina, a semi-rural community in Santiago, Chile. The
      minimal inhibitory concentration of several commonly used antibiotics was
      determined by the agar dilution method. Shigella strains showed high rates of
      resistance to ampicillin (82%), cotrimoxazole (65%), tetracycline (53%), and
      chloramphenicol (49%). Furthermore, 51% of the strains showed resistance patterns
      to multiple antibiotics. Only 9% of the strains were resistant to amoxicillin
      clavulanic acid and no resistance was observed to ciprofloxacin, nalidixic acid,
      or cefotaxime. Continuous monitoring of resistance patterns in Shigella is
      essential for establishing and updating guidelines for antibiotic treatment in
      shigellosis.

PMID- 15964976
TI  - Norwegian scabies in Peru: the impact of human T cell lymphotropic virus type I
      infection.
AB  - Isolates cases and groups of patients co-infected with human T cell lymphotropic
      virus type I (HTLV-I) and Norwegian scabies have been previously reported. Peru
      is considered to be endemic for HTLV-I. Between June 1999 and December 2000, 23
      patients with Norwegian scabies were enrolled in this study after written
      informed consent was obtained. Antibodies against HTLV-I were detected by an
      enzyme-linked immunosorbent assay and confirmatory Western blot. Patients ranged
      in age from 3 months to 84 years; 15 (65.2%) were female. Infection with HTLV-I
      was found in 16 (69.6%) patients. Comorbid features included corticosteroid
      therapy (8.6%), malnutrition (8.6%), and Down's syndrome (4.3%). Among those who
      consented to be tested for human immunodeficiency virus (n = 13, 56.5%), no one
      had a positive result. The three patients that reported one or more prior
      episodes of Norwegian scabies were infected with HTLV-I and two of these HTLV-I
      positive patients died. Infection with HTLV-I is an important co-factor related
      to Norwegian scabies in Peru. In our setting, the evaluation for HTLV-I in all
      Norwegian scabies cases is highly recommended, especially when no other risk
      factors are apparent.

PMID- 15964977
TI  - Are we on track - can we monitor bed targets in the NHS plan for England?
AB  - The NHS plan announced sustained increases in funding accompanied by wide ranging
      reform, the success of which would be measured by targets set across the board,
      including increases in numbers of beds, staff, hospitals and equipment. In this
      article we assess progress towards the target of 7,000 extra beds in hospitals
      and intermediate care to be achieved by 2004. Summary points are as follows. (1)
      Although the 2003/2004 target for availability of general and acute NHS beds in
      England was achieved, the increase did not offset the overall decrease in all
      categories of beds. Bed availability fell by 2083, from 1,86,290 in 1999/2000 to
      1,84,207 in 2003/2004, following a fall of 12,558 from 1996/1997 to 1999/2000.
      (2) Lack of standardized definitions and data collection systems both within the
      NHS and for the independent sector, compounded by ambiguity over the funding of
      extra capacity for the NHS, call into question the accuracy of data collected
      about intermediate care beds. (3) Systems for collecting data about intermediate
      care should be made subject to the same code of practice as official NHS
      statistics in order to monitor future targets and plan for provision of care. (4)
      Changes in definitions, lack of detail about criteria used in setting targets and
      lack of data about private sector care, make it impossible to monitor the overall
      capacity available to the NHS and assess whether bed availability targets have
      been met.

PMID- 15964978
TI  - Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion
      protein.
AB  - Class I viral fusion proteins share common mechanistic and structural features
      but little sequence similarity. Structural insights into the protein
      conformational changes associated with membrane fusion are based largely on
      studies of the influenza virus hemagglutinin in pre- and postfusion
      conformations. Here, we present the crystal structure of the secreted, uncleaved
      ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein,
      a member of the class I viral fusion protein group. The secreted human
      parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk
      regions. Unexpectedly, the structure reveals a six-helix bundle associated with
      the postfusion form of F, suggesting that the anchor-minus ectodomain adopts a
      conformation largely similar to the postfusion state. The transmembrane anchor
      domains of F may therefore profoundly influence the folding energetics that
      establish and maintain a metastable, prefusion state.

PMID- 15964979
TI  - Variable lymphocyte receptors in hagfish.
AB  - A previously uncharacterized type of variable lymphocyte receptors (VLR) was
      identified recently in the Sea lamprey. This jawless vertebrate generates an
      extensive VLR repertoire through differential insertion of neighboring diverse
      leucine-rich repeat (LRR) cassettes into an incomplete germ-line VLR gene. We
      report here VLR homologs from two additional lamprey species and the presence of
      two types of VLR genes in hagfish, the only other order of contemporary jawless
      vertebrates. As in the Sea lamprey, the incomplete hagfish germ-line VLR-A and -B
      genes are modified in lymphocyte-like cells to generate highly diverse
      repertoires of VLR-A and -B proteins via a presently undetermined mechanism. This
      jawless-fish mode of VLR diversification starkly contrasts with the rearrangement
      of Ig V(D)J gene segments used by all jawed vertebrates to produce diverse
      repertoires of T and B lymphocyte antigen receptors. The development of two very
      different strategies for receptor diversification at the dawn of vertebrate
      evolution approximately 500 million years ago attests to the fitness value of a
      lymphocyte-based system of anticipatory immunity.

PMID- 15964980
TI  - Rapid evolutionary radiation of marine zooplankton in peripheral environments.
AB  - Populations of jellyfish, Mastigias sp., landlocked in tropical marine lakes
      during the Holocene, show extreme genetic isolation (0.74 < or = phiST < or =
      1.00), founder effects (genetic diversity: 0.000 < or = pi < or = 0.001), rapid
      morphological evolution, and behavioral adaptation. These results demonstrate
      incipient speciation in what we propose may be modern analogues of Plio
      Pleistocene populations isolated in ocean basins by glacially lowered sea level
      and counterparts to modern marine populations isolated on archipelagos and other
      distant shores. Geographic isolation in novel environments, even if geologically
      brief, may contribute much to marine biodiversity because evolutionary rates in
      marine plankton can rival the most rapid speciation seen for limnetic species,
      such as cichlids and sticklebacks. Marine lakes present situations rare in their
      clarity for studying evolution in marine taxa.

PMID- 15964981
TI  - alpha1-adrenoceptor stimulation potentiates L-type Ca2+ current through
      Ca2+/calmodulin-dependent PK II (CaMKII) activation in rat ventricular myocytes.
AB  - alpha1-Adrenoceptor stimulation (alpha1ARS) modulates cardiac muscle contraction
      under physiological conditions by means of changes in Ca2+ current through L-type
      channels (ICa,L) and Ca2+ sensitivity of the myofilaments. However, the cellular
      mechanisms of alpha1ARS are not fully clarified. In this study, we investigated
      the role of Ca2+/calmodulin-dependent PK II (CaMKII) in the regulation of ICa,L
      during alpha1ARS in isolated adult rat ventricular myocytes by using the
      perforated patch-clamp technique. CaMKII inhibition with 0.5 microM KN-93
      abolished the potentiation in ICa,L observed during alpha1ARS by 10 microM
      phenylephrine. In the presence of PKC inhibitor (10 microM chelerythrine), the
      potentiation of ICa,L by phenylephrine also disappeared. In Western
      immunoblotting analysis, phenylephrine (> or =1 microM) increased the amount of
      autophosphorylated CaMKII (active CaMKII) significantly, and this increase was
      abolished by CaMKII inhibition or PKC inhibition. Also, we investigated changes
      in the subcellular localization of active CaMKII by using immunofluorescence
      microscopy and immunoelectron microscopy. Before alpha1ARS, active CaMKII was
      exclusively located just beneath the plasmalemma. However, after alpha1ARS,
      active CaMKII was localized close to transverse tubules, where most of L-type
      Ca2+ channels are located. From these results, we propose that CaMKII, which
      exists near transverse tubules, is activated and phosphorylated by alpha1ARS and
      that CaMKII activation directly potentiates ICa,L in rat ventricular myocytes.

PMID- 15964982
TI  - The Plasmodium falciparum cysteine protease falcipain-2 captures its substrate,
      hemoglobin, via a unique motif.
AB  - Falcipain-2 (FP2) is a papain family cysteine protease and important
      hemoglobinase of erythrocytic Plasmodium falciparum parasites. Inhibitors of FP2
      block hemoglobin hydrolysis and parasite development, suggesting that this enzyme
      is a promising target for antimalarial chemotherapy. FP2 and related plasmodial
      cysteine proteases have an unusual 14-aa motif near the C terminus of the
      catalytic domain. Recent solution of the structure of FP2 showed this motif to
      form a beta-hairpin that is distant from the enzyme active site and protrudes out
      from the protein. To evaluate the function of this motif, we compared the
      activity of the wild-type enzyme with that of a mutant lacking 10 aa of the motif
      (Delta10FP2). Delta10FP2 had nearly identical activity to that of the wild-type
      enzyme against peptide substrates and the protein substrates casein and gelatin.
      However, Delta10FP2 demonstrated negligible activity against hemoglobin or
      globin. FP2 that was inhibited with trans-epoxysuccinyl-L-leucylamido-(4
      guanidino)butane (FP2E-64) formed a complex with hemoglobin, but Delta10FP2E-64
      did not, indicating that the motif mediates binding to hemoglobin independent of
      the active site. A peptide encoding the motif blocked hemoglobin hydrolysis, but
      not the hydrolysis of casein. Kinetics for the inhibition of Delta10FP2 were very
      similar to those for FP2 with peptidyl and protein inhibitors, but Delta10FP2 was
      poorly inhibited by the inhibitory prodomain of FP2. Our results indicate that
      FP2 utilizes an unusual motif for two specific functions, interaction with
      hemoglobin, its natural substrate, and interaction with the prodomain, its
      natural inhibitor.

PMID- 15964983
TI  - Structure of a peptide:N-glycanase-Rad23 complex: insight into the
      deglycosylation for denatured glycoproteins.
AB  - In eukaryotes, misfolded proteins must be distinguished from correctly folded
      proteins during folding and transport processes by quality control systems. Yeast
      peptide:N-glycanase (yPNGase) specifically deglycosylates the denatured form of N
      linked glycoproteins in the cytoplasm and assists proteasome-mediated
      glycoprotein degradation by forming a complex with 26S proteasome through DNA
      repair protein, yRad23. Here, we describe the crystal structures of a yPNGase and
      XPC-binding domain of yRad23 (yRad23XBD, residues 238-309) complex and of a
      yPNGase-yRad23XBD complex bound to a caspase inhibitor, Z-VAD-fmk. yPNGase is
      formed with three domains, a core domain containing a Cys-His-Asp triad, a Zn
      binding domain, and a Rad23-binding domain. Both N- and C-terminal helices of
      yPNGase interact with yRad23 through extensive hydrophobic interactions. The
      active site of yPNGase is located in a deep cleft that is formed with residues
      conserved in all PNGase members, and three sugar molecules are bound to this
      cleft. Complex structures in conjunction with mutational analyses revealed that
      the walls of the cleft block access to the active site of yPNGase by native
      glycoprotein, whereas the cleft is sufficiently wide to accommodate denatured
      glycoprotein, thus explaining the specificity of PNGase for denatured substrates.

PMID- 15964984
TI  - Mountain gorilla tug-of-war: silverbacks have limited control over reproduction
      in multimale groups.
AB  - To determine who fathers the offspring in wild mountain gorilla groups containing
      more than one adult male silverback, we genotyped nearly one-fourth (n = 92) of
      the mountain gorillas (Gorilla beringei beringei) living in the Virunga Volcanoes
      region of Africa. Paternity analysis of 48 offspring born into four groups
      between 1985 and 1999 revealed that, although all infants were sired by within
      group males, the socially dominant silverback did not always monopolize
      reproduction within his group. Instead, the second-ranking male sired an average
      of 15% of group offspring. This result, in combination with previous findings
      that second-ranking males fare best by not leaving the group but by staying and
      waiting to assume dominance even if no reproduction is possible while waiting, is
      not consistent with expectations from a reproductive skew model in which the
      silverback concedes controllable reproduction to the second-ranking male.
      Instead, the data suggest a "tug-of-war" scenario in which neither the dominant
      nor the second-ranking male has full control over his relative reproductive
      share. The two top-ranked males were typically unrelated and this, in combination
      with the mixed paternity of group offspring, means that multimale gorilla groups
      do not approximate family groups. Instead, as long-term assemblages of related
      and unrelated individuals, gorilla groups are similar to chimpanzee groups and so
      offer interesting possibilities for kin-biased interactions among individuals.

PMID- 15964985
TI  - Structural basis for photo-induced protein cleavage and green-to-red conversion
      of fluorescent protein EosFP.
AB  - Genetically encoded fusion constructs derived from fluorescent proteins (FPs) can
      be designed to report on a multitude of events and signals in cells, tissues, and
      entire organs without interfering with the complex machinery of life. EosFP is a
      novel FP from the scleractinian coral Lobophyllia hemprichii that switches its
      fluorescence emission from green (516 nm) to red (581 nm) upon irradiation with
      approximately 400-nm light. This property enables localized tagging of proteins
      and thus provides a valuable tool for tracking protein movements within live
      cells. Here, we present the x-ray structures of the green and red forms of WT
      EosFP. They reveal that formation of the red chromophore is associated with
      cleavage of the peptide backbone, with surprisingly little change elsewhere in
      the structure, and provide insights into the mechanism that generates this
      interesting posttranslational polypeptide modification.

PMID- 15964986
TI  - Contribution of the tetrodotoxin-resistant voltage-gated sodium channel NaV1.9 to
      sensory transmission and nociceptive behavior.
AB  - The transmission of pain signals after injury or inflammation depends in part on
      increased excitability of primary sensory neurons. Nociceptive neurons express
      multiple subtypes of voltage-gated sodium channels (NaV1s), each of which
      possesses unique features that may influence primary afferent excitability. Here,
      we examined the contribution of NaV1.9 to nociceptive signaling by studying the
      electrophysiological and behavioral phenotypes of mice with a disruption of the
      SCN11A gene, which encodes NaV1.9. Our results confirm that NaV1.9 underlies the
      persistent tetrodotoxin-resistant current in small-diameter dorsal root ganglion
      neurons but suggest that this current contributes little to mechanical thermal
      responsiveness in the absence of injury or to mechanical hypersensitivity after
      nerve injury or inflammation. However, the expression of NaV1.9 contributes to
      the persistent thermal hypersensitivity and spontaneous pain behavior after
      peripheral inflammation. These results suggest that inflammatory mediators modify
      the function of NaV1.9 to maintain inflammation-induced hyperalgesia.

PMID- 15964987
TI  - Altering cannabinoid signaling during development disrupts neuronal activity.
AB  - In adult cortical tissue, recruitment of GABAergic inhibition prevents the
      progression of synchronous population discharges to epileptic activity. However,
      at early developmental stages, GABA is excitatory and thus unable to fulfill this
      role. Here, we report that retrograde signaling involving endocannabinoids is
      responsible for the homeostatic control of synaptic transmission and the
      resulting network patterns in the immature hippocampus. Blockade of cannabinoid
      type 1 (CB1) receptor led to epileptic discharges, whereas overactivation of CB1
      reduced network activity in vivo. Endocannabinoid signaling thus is able to keep
      population discharge patterns within a narrow physiological time window,
      balancing between epilepsy on one side and sparse activity on the other, which
      may result in impaired developmental plasticity. Disturbing this delicate balance
      during pregnancy in either direction, e.g., with marijuana as a CB1 agonist or
      with an antagonist marketed as an antiobesity drug, can have profound
      consequences for brain maturation even in human embryos.

PMID- 15964988
TI  - 1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4
      nitrophenyl)ethoxy]carbonyl]hydrazine: an anticancer agent targeting hypoxic
      cells.
AB  - To target malignant cells residing in hypoxic regions of solid tumors, we have
      designed and synthesized prodrugs generating the cytotoxic alkylating species 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)hydrazine (90CE) after bioreductive
      activation. We postulate that one of these agents, 1,2-bis(methylsulfonyl)-1-(2
      chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119), requires
      enzymatic nitro reduction to produce 90CE, whereas another agent, 1,2
      bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(4-nitrobenzyloxy)carbonyl]hydrazine
      (PNBC), can also be activated by nucleophilic attack by thiols such as
      glutathione (GSH)/GST. We demonstrated that these agents selectively kill hypoxic
      EMT6 mouse mammary carcinoma and CHO cells. In hypoxia, 50 microM KS119 produced
      5 logs of kill of EMT6 cells without discernable cytotoxicity in air; similar
      effects were observed with CHO cells. PNBC was less efficacious against hypoxic
      tumor cells and also had some toxicity to aerobic cells, presumably because of
      GST/thiol activation, making PNBC less interesting as a selective hypoxic-cell
      cytotoxin. BALB/c mice with established EMT6 solid tumors were used to
      demonstrate that KS119 could reach and kill hypoxic cells in solid tumors. To
      gain information on bioreductive enzymes involved in the activation of KS119,
      cytotoxicity was measured in CHO cell lines overexpressing NADH:cytochrome b5
      reductase (NBR), NADPH:cytochrome P450 reductase (NPR), or NADPH: quinone
      oxidoreductase 1 (NQO1). Increased cytotoxicity occurred in cells overexpressing
      NBR and NPR, whereas overexpressed NQO1 had no effect. These findings were
      supported by enzymatic studies using purified NPR and xanthine oxidase to
      activate KS119. KS119 has significant potential as a hypoxia-selective tumor-cell
      cytotoxin and is unlikely to cause major toxicity to well oxygenated normal
      tissues.

PMID- 15964989
TI  - Plant coexistence depends on ecosystem nutrient cycles: extension of the resource
      ratio theory.
AB  - We present a model of plant-nutrient interactions that extends classical resource
      competition theory to environments in which essential nutrients (resources) are
      recycled between plant and soil pools and dissolved nutrients are lost through
      plant-available (i.e., inorganic forms) or plant-unavailable (i.e., complex
      organic forms) pathways. Losses by dissolved organic pathways can alter ratios of
      nutrients that are recycled and supplied within the plant-soil system, thereby
      influencing competition and coexistence among plant species. In special cases,
      our extended model does not differ from classical models, but in more realistic
      cases our model introduces new dynamical behavior that influences competitive
      outcomes. At equilibrium, coexistence still depends on nutrient supply and
      consumption, but nutrient supply includes recycling and is highly sensitive to
      whether a species promotes more organic losses of the nutrient that limits its
      own growth than of nutrients that limit its competitors. Because recycling
      operates with a time delay compared with consumption, recycling-mediated effects
      on competition can, under certain conditions, lead to sustained population
      oscillations. Our findings have implications for how we understand nutrient
      competition, nutrient cycles, and plant evolutionary strategies.

PMID- 15964990
TI  - Pulmonary fibrosis: searching for model answers.
AB  - Substantial challenges remain in our understanding of fibrotic lung diseases.
      Nowhere is this more true than in the elucidation and verification of the
      pathogenetic basis upon which they develop. Scientific progress, most recently in
      the field of experimental therapy, has relied closely on interpreting data
      derived from animal modeling. Such models are used to identify the cellular
      interactions and molecular pathways involved in lung tissue repair and fibrosis.
      Over the coming years, the significance of new discoveries will continue to be
      evaluated using the in vivo analysis of animal models substituting for patients
      with actual pulmonary fibrosis. The commonest strategy to induce experimental
      pulmonary fibrosis is by directly administering a profibrotic agent to either
      wild-type animals or those that bear a specific genetic modification. The
      creation of new models has been greatly enhanced by the availability of stem cell
      lines and methods for introducing genetic mutations into these cells. Despite an
      increasing choice of models, there are still good reasons to continue adapting
      and using one of its earliest examples, the bleomycin model, in post-genomic
      pulmonary fibrosis research. A brief review of the exacting requirements of such
      research will place the strengths of this particular model in perspective.

PMID- 15964991
TI  - A structural perspective of CTD function.
AB  - The C-terminal domain (CTD) of RNA polymerase II (Pol II) integrates nuclear
      events by binding proteins involved in mRNA biogenesis. CTD-binding proteins
      recognize a specific CTD phosphorylation pattern, which changes during the
      transcription cycle, due to the action of CTD-modifying enzymes. Structural and
      functional studies of CTD-binding and -modifying proteins now reveal some of the
      mechanisms underlying CTD function. Proteins recognize CTD phosphorylation
      patterns either directly, by contacting phosphorylated residues, or indirectly,
      without contact to the phosphate. The catalytic mechanisms of CTD kinases and
      phosphatases are known, but the basis for CTD specificity of these enzymes
      remains to be understood.

PMID- 15964992
TI  - Guanosine triphosphate acts as a cofactor to promote assembly of initial P
      element transposase-DNA synaptic complexes.
AB  - P transposable elements in Drosophila are members of a larger class of mobile
      elements that move using a cut-and-paste mechanism. P-element transposase uses
      guanosine triphosphate (GTP) as a cofactor for transposition. Here, we use atomic
      force microscopy (AFM) to visualize protein-DNA complexes formed during the
      initial stages of P-element transposition. These studies reveal that GTP acts to
      promote assembly of the first detectable noncovalent precleavage synaptic
      complex. This initial complex then randomly and independently cleaves each P
      element end. These data show that GTP acts to promote protein-DNA assembly, and
      may explain why P-element excision often leads to unidirectional deletions.

PMID- 15964993
TI  - Pax3/Pax7 mark a novel population of primitive myogenic cells during development.
AB  - Skeletal muscle serves as a paradigm for the acquisition of cell fate, yet the
      relationship between primitive cell populations and emerging myoblasts has
      remained elusive. We identify a novel population of resident Pax3+/Pax7+, muscle
      marker-negative cells throughout development. Using mouse mutants that uncouple
      myogenic progression, we show that these Pax+ cells give rise to muscle
      progenitors. In the absence of skeletal muscle, they apoptose after down
      regulation of Pax7. Furthermore, they mark the emergence of satellite cells
      during fetal development, and do not require Pax3 function. These findings
      identify critical cell populations during lineage restriction, and provide a
      framework for defining myogenic cell states for therapeutic studies.

PMID- 15964994
TI  - Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse
      growth and survival by repressing the p16Ink4a and p19Arf senescence pathways.
AB  - Bmi-1 is required for the post-natal maintenance of stem cells in multiple
      tissues including the central nervous system (CNS) and peripheral nervous system
      (PNS). Deletion of Ink4a or Arf from Bmi-1(-/-) mice partially rescued stem cell
      self-renewal and stem cell frequency in the CNS and PNS, as well as forebrain
      proliferation and gut neurogenesis. Arf deficiency, but not Ink4a deficiency,
      partially rescued cerebellum development, demonstrating regional differences in
      the sensitivity of progenitors to p16Ink4a and p19Arf. Deletion of both Ink4a and
      Arf did not affect the growth or survival of Bmi-1(-/-) mice or completely rescue
      neural development. Bmi-1 thus prevents the premature senescence of neural stem
      cells by repressing Ink4a and Arf, but additional pathways must also function
      downstream of Bmi-1.

PMID- 15964995
TI  - Ink4a and Arf differentially affect cell proliferation and neural stem cell self
      renewal in Bmi1-deficient mice.
AB  - The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self
      renewal by repressing the Ink4a/Arf locus. We used a genetic approach to
      investigate whether Ink4a or Arf is more critical for relaying Bmi1 function in
      lymphoid cells, neural progenitors, and neural stem cells. We show that Arf is a
      general target of Bmi1, however particularly in neural stem cells, derepression
      of Ink4a contributes to Bmi1(-/-) phenotypes. Additionally, we demonstrate
      haploinsufficient effects for the Ink4a/Arf locus downstream of Bmi1 in vivo.
      This suggests differential, cell type-specific roles for Ink4a versus Arf in PcG
      mediated (stem) cell cycle control.

PMID- 15964996
TI  - Activation of nuclear receptor coactivator PGC-1alpha by arginine methylation.
AB  - Peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha),
      a tissue-specific and inducible transcriptional coactivator for several nuclear
      receptors, plays a key role in energy metabolism. We report here that PGC-1alpha
      coactivator activity is potentiated by arginine methylation by protein arginine
      methyltransferase 1 (PRMT1), another nuclear receptor coactivator. Mutation of
      three substrate arginines in the C-terminal region of PGC-1alpha abolished the
      cooperative coactivator function of PGC-1alpha and PRMT1, and compromised the
      ability of PGC-1alpha to induce endogenous target genes. Finally, endogenous
      PRMT1 contributes to PGC-1alpha coactivator activity, and to the induction of
      genes important for mitochondrial biogenesis.

PMID- 15964997
TI  - Tsix transcription across the Xist gene alters chromatin conformation without
      affecting Xist transcription: implications for X-chromosome inactivation.
AB  - X-chromosome inactivation (XCI) is highly dynamic during early mouse
      embryogenesis and strictly depends on the Xist noncoding RNA. The regulation of
      Xist and its antisense partner Tsix remains however poorly understood. We provide
      here the first evidence of transcriptional control of Xist expression. We show
      that RNA polymerase II (RNAPolII) preinitiation complex recruitment and H3 Lys 4
      (H3-K4) methylation at the Xist promoter form the basis of the Xist expression
      profiles that drives both imprinted and random XCI. In embryonic stem (ES) cells,
      which are derived from the inner cell mass where imprinted XCI is reversed and
      both Xs are active, we show that Xist is repressed at the level of preinitiation
      complex (PIC) recruitment. We further demonstrate that Tsix, although highly
      transcribed in ES cells, is not itself responsible for the transcriptional down
      regulation of Xist. Rather, Tsix induces efficient H3-K4 methylation over the
      entire Xist/Tsix unit. We suggest that chromatin remodeling of the Xist locus
      induced by biallelic Tsix transcription renders both Xist loci epigenetically
      equivalent and equally competent for transcription. In this model, Tsix, by
      resetting the epigenetic state of the Xist/Tsix locus, mediates the transition
      from imprinted to random XCI.

PMID- 15965003
TI  - The 2001 epidemic of foot-and-mouth disease in the United Kingdom:
      epidemiological and meteorological case studies.
AB  - The possibility of the airborne spread of foot-and-mouth disease during the 2001
      epidemic in the uk has been investigated in three epidemiological case studies.
      On the basis of evidence from field investigations, and a simple meteorological
      analysis, it is concluded that the spread of disease was consistent with the
      airborne transport of virus. The distances ranged from less than 1 km to 16 km;
      six of the farms were over 6 km from the source and involved the passage of virus
      over the sea combined with meteorological conditions which strongly favoured
      airborne disease transmission. The results of detailed atmospheric modelling
      demonstrated that airborne virus could have challenged livestock on all the farms
      studied. However, with one exception the 24-hour average daily concentrations of
      the virus were significantly below the experimentally estimated threshold for
      infection. A detailed model intercomparison established that, under stable
      atmospheric conditions, peak concentrations of virus up to two orders of
      magnitude higher might have been experienced for short periods, owing to
      fluctuations within the plume of virus, and model limitations. This finding would
      significantly reduce the apparent discrepancy between the experimentally
      estimated threshold for infection and the modelling results.

PMID- 15965004
TI  - Clinical investigation of remifentanil and propofol for the total intravenous
      anaesthesia of dogs.
AB  - Fifteen adult dogs underwent elective ovariectomy. They were premedicated with
      0.5 mg/kg methadone and 0.05 mg/kg(-1) atropine administered intramuscularly, and
      anaesthesia was induced with propofol and maintained with intravenous infusions
      of remifentanil at 0.6 microg/kg/minute and propofol; the mean (sd) rate of
      infusion of propofol throughout the period of anaesthesia was 0.33 (0.03)
      mg/kg/minute. The dogs were ventilated continuously with oxygen while they were
      anaesthetised. Their haemodynamic parameters were clinically acceptable during
      the period of anaesthesia. Two dogs received additional atropine to correct
      bradycardias of less than 60 bpm and several dogs received additional boluses of
      remifentanil or propofol to maintain an adequate depth of anaesthesia, as
      determined by a clinical assessment. The mean (range) time to the return of
      spontaneous respiration after stopping the remifentanil infusion was 11.1 (6.0 to
      17.0) minutes, and the mean (range) time to the dogs standing was 38.0 (20.0 to
      80.0) minutes. The quality of recovery was good in 12 of the dogs, two showed
      mild excitation in the immediate postoperative period and the other dog required
      additional analgesia with methadone.

PMID- 15964998
TI  - p21WAF1/Cip1 is a negative transcriptional regulator of Wnt4 expression
      downstream of Notch1 activation.
AB  - In keratinocytes, the cyclin/CDK inhibitor p21(WAF1/Cip1) is a direct
      transcriptional target of Notch1 activation; loss of either the p21 or Notch1
      genes expands stem cell populations and facilitates tumor development. The Notch1
      tumor-suppressor function was associated with down-regulation of Wnt signaling.
      Here, we show that suppression of Wnt signaling by Notch1 activation is mediated,
      at least in part, by down-modulation of Wnts gene expression. p21 is a negative
      regulator of Wnts transcription downstream of Notch1 activation, independently of
      effects on the cell cycle. More specifically, expression of the Wnt4 gene is
      under negative control of endogenous p21 both in vitro and in vivo. p21
      associates with the E2F-1 transcription factor at the Wnt4 promoter and causes
      curtailed recruitment of c-Myc and p300, and histone hypoacetylation at this
      promoter. Thus, p21 acts as a selective negative regulator of transcription and
      links the Notch and Wnt signaling pathways in keratinocyte growth control.

PMID- 15965005
TI  - Long-term effects of meloxicam in the treatment of respiratory disease in
      fattening cattle.
AB  - The long-term effects of a single dose of meloxicam (Metacam 20 mg/ml; Boehringer
      Ingelheim Vetmedica) in conjunction with antibiotic therapy in cattle with
      clinical signs of bovine respiratory disease (BRD) was evaluated in a blind,
      controlled, randomised study. Two hundred animals with clinical signs of brd
      received a single subcutaneous injection of 20 mg/kg oxytetracycline; 100 of them
      also received a subcutaneous injection of 0.5 mg/kg meloxicam, and the other 100
      received an injection of isotonic saline. The animals were weighed before they
      were treated and seven, 35, 70 and 105 days later, and finally before they were
      slaughtered. The mean bodyweight of the meloxicam-treated animals was
      significantly higher from day 70 until slaughter, and the mean average daily
      weight gain until slaughter and the mean carcase weight of the animals treated
      with meloxicam were significantly higher. In the animals with lung lesions,
      significantly less lung tissue was affected in those that had been treated with
      meloxicam.

PMID- 15965006
TI  - Outbreak of Candida rugosa mastitis in a dairy herd after intramammary antibiotic
      treatment.

PMID- 15965008
TI  - Removal of RCVS members.

PMID- 15965009
TI  - Cost of the practice pharmacy.

PMID- 15965010
TI  - Prevalence of gastrointestinal parasites in horses.

PMID- 15965011
TI  - Low bulk milk urea in dairy herds.

PMID- 15965013
TI  - D-lactate metabolism and the clinical signs of D-lactataemia in calves.

PMID- 15965014
TI  - Profile and analysis of gene expression changes during early development in
      germinating spores of Ceratopteris richardii.
AB  - Analysis of an expressed sequence tag library with more than 5,000 sequences from
      spores of the fern Ceratopteris richardii reveals that more than 3,900 of them
      represent distinct genes, and almost 70% of these have significant similarity to
      Arabidopsis (Arabidopsis thaliana) genes. Eight genes are common between three
      very different dormant plant systems, Ceratopteris spores, Arabidopsis seeds, and
      Arabidopsis pollen. We evaluated the pattern of mRNA abundance over the first 48
      h of spore development using a microarray of cDNAs representing 3,207 distinct
      genes of C. richardii and determined the relative levels of RNA abundance for
      3,143 of these genes using a Bayesian method of statistical analysis. More than
      900 of them (29%) show a significant change between any of the five time points
      analyzed, and these have been annotated based on their sequence similarity with
      the Arabidopsis proteome. Novel data arising from these analyses identify genes
      likely to be critical for the germination and subsequent early development of
      diverse cells and tissues emerging from dormancy.

PMID- 15965015
TI  - Tocopherols protect Synechocystis sp. strain PCC 6803 from lipid peroxidation.
AB  - Tocopherols (vitamin E) are lipid-soluble antioxidants synthesized only by
      photosynthetic eukaryotes and some cyanobacteria, and have been assumed to play
      important roles in protecting photosynthetic membranes from oxidative stress. To
      test this hypothesis, tocopherol-deficient mutants of Synechocystis sp. strain
      PCC 6803 (slr1736 and slr1737 mutants) were challenged with a series of reactive
      oxygen species-generating and lipid peroxidation-inducing chemicals in
      combination with high-light (HL) intensity stress. The tocopherol-deficient
      mutants and wild type were indistinguishable in their growth responses to HL in
      the presence and absence of superoxide and singlet oxygen-generating chemicals.
      However, the mutants showed enhanced sensitivity to linoleic or linolenic acid
      treatments in combination with HL, consistent with tocopherols playing a crucial
      role in protecting Synechocystis sp. strain PCC 6803 cells from lipid
      peroxidation. The tocopherol-deficient mutants were also more susceptible to HL
      treatment in the presence of sublethal levels of norflurazon, an inhibitor of
      carotenoid synthesis, suggesting carotenoids and tocopherols functionally
      interact or have complementary or overlapping roles in protecting Synechocystis
      sp. strain PCC 6803 from lipid peroxidation and HL stress.

PMID- 15965016
TI  - Compilation of mRNA polyadenylation signals in Arabidopsis revealed a new signal
      element and potential secondary structures.
AB  - Using a novel program, SignalSleuth, and a database containing authenticated
      polyadenylation [poly(A)] sites, we analyzed the composition of mRNA poly(A)
      signals in Arabidopsis (Arabidopsis thaliana), and reevaluated previously
      described cis-elements within the 3'-untranslated (UTR) regions, including near
      upstream elements and far upstream elements. As predicted, there are absences of
      high-consensus signal patterns. The AAUAAA signal topped the near upstream
      elements patterns and was found within the predicted location to only
      approximately 10% of 3'-UTRs. More importantly, we identified a new set, named
      cleavage elements, of poly(A) signals flanking both sides of the cleavage site.
      These cis-elements were not previously revealed by conventional mutagenesis and
      are contemplated as a cluster of signals for cleavage site recognition. Moreover,
      a single-nucleotide profile scan on the 3'-UTR regions unveiled a distinct
      arrangement of alternate stretches of U and A nucleotides, which led to a
      prediction of the formation of secondary structures. Using an RNA secondary
      structure prediction program, mFold, we identified three main types of secondary
      structures on the sequences analyzed. Surprisingly, these observed secondary
      structures were all interrupted in previously constructed mutations in these
      regions. These results will enable us to revise the current model of plant
      poly(A) signals and to develop tools to predict 3'-ends for gene annotation.

PMID- 15965017
TI  - Phytic acid synthesis and vacuolar accumulation in suspension-cultured cells of
      Catharanthus roseus induced by high concentration of inorganic phosphate and
      cations.
AB  - We have established a new system for studying phytic acid, myo-inositol
      hexakisphosphate (InsP(6)) synthesis in suspension-cultured cells of
      Catharanthus. InsP(6) and other intermediates of myo-inositol (Ins) phosphate
      metabolism were measured using an ion chromatography method. The detection limit
      for InsP(6) was less than 50 nM, which was sufficient to analyze Ins phosphates
      in living cells. Synthesis of Ins phosphates was induced by incubation in high
      inorganic phosphate medium. InsP(6) was mainly accumulated in vacuoles and was
      enhanced when cells were grown in high concentration of inorganic phosphates with
      the cations K(+), Ca(2+), or Zn(2+). However, there was a strong tendency for
      InsP(6) to accumulate in the vacuole in the presence of Ca(2+) and in nonvacuolar
      compartments when supplied with Zn(2+), possibly due to precipitation of InsP(6)
      with Zn(2+) in the cytosol. A vesicle transport inhibitor, brefeldin A,
      stimulated InsP(6) accumulation. The amounts of both Ins(3)P(1) myo-inositol
      monophosphate synthase, a key enzyme for InsP(6) synthesis, and Ins(1,4,5)P(3)
      kinase were unrelated to the level of accumulation of InsP(6). The mechanisms for
      InsP(6) synthesis and localization into vacuoles in plant cells are discussed.

PMID- 15965018
TI  - Atypical regulation of a green lineage-specific B-type cyclin-dependent kinase.
AB  - Cyclin-dependent kinases (CDKs) are the main regulators of cell cycle progression
      in eukaryotes. The role and regulation of canonical CDKs, such as the yeast
      (Saccharomyces cerevisiae) Cdc2 or plant CDKA, have been extensively
      characterized. However, the function of the plant-specific CDKB is not as well
      understood. Besides being involved in cell cycle control, Arabidopsis
      (Arabidopsis thaliana) CDKB would integrate developmental processes to cell cycle
      progression. We investigated the role of CDKB in Ostreococcus (Ostreococcus
      tauri), a unicellular green algae with a minimal set of cell cycle genes. In this
      primitive alga, at the basis of the green lineage, CDKB has integrated two levels
      of regulations: It is regulated by Tyr phosphorylation like cdc2/CDKA and at the
      level of synthesis-like B-type CDKs. Furthermore, Ostreococcus CDKB/cyclin B
      accounts for the main peak of mitotic activity, and CDKB is able to rescue a
      yeast cdc28(ts) mutant. By contrast, Ostreococcus CDKA is not regulated by Tyr
      phosphorylation, and it exhibits a low and steady-state activity from DNA
      replication to exit of mitosis. This suggests that from a major role in the
      control of mitosis in green algae, CDKB has evolved in higher plants to assume
      other functions outside the cell cycle.

PMID- 15965019
TI  - Surrogate splicing for functional analysis of sesquiterpene synthase genes.
AB  - A method for the recovery of full-length cDNAs from predicted terpene synthase
      genes containing introns is described. The approach utilizes Agrobacterium
      mediated transient expression coupled with a reverse transcription
      polydeoxyribonucleotide chain reaction assay to facilitate expression cloning of
      processed transcripts. Subsequent expression of intronless cDNAs in a suitable
      prokaryotic host provides for direct functional testing of the encoded gene
      product. The method was optimized by examining the expression of an intron
      containing beta-glucuronidase gene agroinfiltrated into petunia (Petunia hybrida)
      leaves, and its utility was demonstrated by defining the function of two
      previously uncharacterized terpene synthases. A tobacco (Nicotiana tabacum)
      terpene synthase-like gene containing six predicted introns was characterized as
      having 5-epi-aristolochene synthase activity, while an Arabidopsis (Arabidopsis
      thaliana) gene previously annotated as a terpene synthase was shown to possess a
      novel sesquiterpene synthase activity for alpha-barbatene, thujopsene, and beta
      chamigrene biosynthesis.

PMID- 15965021
TI  - Auxin dynamics after decapitation are not correlated with the initial growth of
      axillary buds.
AB  - One of the first and most enduring roles identified for the plant hormone auxin
      is the mediation of apical dominance. Many reports have claimed that reduced stem
      indole-3-acetic acid (IAA) levels and/or reduced basipetal IAA transport directly
      or indirectly initiate bud growth in decapitated plants. We have tested whether
      auxin inhibits the initial stage of bud release, or subsequent stages, in garden
      pea (Pisum sativum) by providing a rigorous examination of the dynamics of auxin
      level, auxin transport, and axillary bud growth. We demonstrate that after
      decapitation, initial bud growth occurs prior to changes in IAA level or
      transport in surrounding stem tissue and is not prevented by an acropetal supply
      of exogenous auxin. We also show that auxin transport inhibitors cause a similar
      auxin depletion as decapitation, but do not stimulate bud growth within our
      experimental time-frame. These results indicate that decapitation may trigger
      initial bud growth via an auxin-independent mechanism. We propose that auxin
      operates after this initial stage, mediating apical dominance via autoregulation
      of buds that are already in transition toward sustained growth.

PMID- 15965020
TI  - The histidine kinase Hik34 is involved in thermotolerance by regulating the
      expression of heat shock genes in synechocystis.
AB  - Histidine kinases (Hiks) in Synechocystis sp. PCC 6803 are involved in the
      transduction of signals associated with various kinds of environmental stress. To
      examine the potential role in thermotolerance of Hiks, we used genome microarray
      analysis to screen a Hik knockout library for mutations that affected the
      expression of genes for heat shock proteins. Mutation of the hik34 gene enhanced
      the levels of transcripts of a number of heat shock genes, including htpG and
      groESL1. Overexpression of the hik34 gene repressed the expression of these heat
      shock genes. In addition, the cells with a mutant gene for Hik34 (DeltaHik34
      cells) survived incubation at 48 degrees C for 3 h, while wild-type cells and
      cells with mutations in other Hiks were killed. However, mutation of the hik34
      gene had only an insignificant effect on the global expression of genes upon
      incubation of the mutant cells at 44 degrees C for 20 min. Quantitative two
      dimensional gel electrophoresis revealed that levels of GroES and HspA were
      elevated in DeltaHik34 cells after incubation of cells at 42 degrees C for 60
      min. We overexpressed recombinant Hik34 protein in Escherichia coli and purified
      it. We found that the protein was autophosphorylated in vitro at physiological
      temperatures, but not at elevated temperatures, such as 44 degrees C. These
      results suggest that Hik34 might negatively regulate the expression of certain
      heat shock genes that might be related to thermotolerance in Synechocystis.

PMID- 15965022
TI  - A RING domain gene is expressed in different cell types of leaf trace, stem, and
      juvenile bundles in the stem vascular system of zinnia.
AB  - The in vitro zinnia (Zinnia elegans) mesophyll cell system, in which leaf
      mesophyll cells are induced to transdifferentiate into tracheary elements with
      high synchrony, has become an established model for studying xylogenesis. The
      architecture of the stem vascular system of zinnia cv Envy contains three
      anatomically distinct vascular bundles at different stages of development.
      Juvenile vascular strands of the subapical region develop into mature vascular
      strands with leaf trace segments and stem segments. Characteristic patterns of
      gene expression in juvenile, leaf trace, and stem bundles are revealed by a
      molecular marker, a RING domain-encoding gene, ZeRH2.1, originally isolated from
      a zinnia cDNA library derived from differentiating in vitro cultures. Using RNA
      in situ hybridization, we show that ZeRH2.1 is expressed preferentially in two
      specific cell types in mature zinnia stems. In leaf trace bundles, ZeRH2.1
      transcript is abundant in xylem parenchyma cells, while in stem bundles it is
      abundant in phloem companion cells. Both of these cell types show wall ingrowths
      characteristic of transfer cells. In addition, ZeRH2.1 transcript is abundant in
      some phloem cells of juvenile bundles and in leaf palisade parenchyma. The
      complex and developmentally regulated expression pattern of ZeRH2.1 reveals
      heterogeneity in the vascular anatomy of the zinnia stem. We discuss a potential
      function for this gene in intercellular transport processes.

PMID- 15965023
TI  - Localized hormone fluxes and early haustorium development in the hemiparasitic
      plant Triphysaria versicolor.
AB  - Perhaps the most obvious phenotypes associated with chemical signaling between
      plants are manifested by parasitic species of Orobanchaceae. The development of
      haustoria, invasive root structures that allow hemiparasitic plants to transition
      from autotrophic to heterotrophic growth, is rapid, highly synchronous, and
      readily observed in vitro. Haustorium development is initiated in aseptic roots
      of the facultative parasite Triphysaria versicolor when exposed to phenolic
      molecules associated with host root exudates and rhizosphere bioactivity.
      Morphological features of early haustorium ontogeny include rapid cessation of
      root elongation, expansion, and differentiation of epidermal cells into
      haustorial hairs, and cortical cell expansion. These developmental processes were
      stimulated in aseptic T. versicolor seedlings by the application of exogenous
      phytohormones and inhibited by the application of hormone antagonists. Surgically
      dissected root tips formed haustoria if the root was exposed to haustorial
      inducing factors prior to dissection. In contrast, root tips that were dissected
      prior to inducing-factor treatment were unable to form haustoria unless
      supplemented with indole-3-acetic acid. A transient transformation assay
      demonstrated that auxin and ethylene-responsive promoters were up-regulated when
      T. versicolor was exposed to either exogenous hormones or purified haustoria
      inducing factors. These experiments demonstrate that localized auxin and ethylene
      accumulation are early events in haustorium development and that parasitic plants
      recruit established plant developmental mechanisms to realize parasite-specific
      functions.

PMID- 15965024
TI  - The maize root transcriptome by serial analysis of gene expression.
AB  - Serial Analysis of Gene Expression was used to define number and relative
      abundance of transcripts in the root tip of well-watered maize seedlings (Zea
      mays cv FR697). In total, 161,320 tags represented a minimum of 14,850 genes,
      based on at least two tags detected per transcript. The root transcriptome has
      been sampled to an estimated copy number of approximately five transcripts per
      cell. An extrapolation from the data and testing of single-tag identifiers by
      reverse transcription-PCR indicated that the maize root transcriptome should
      amount to at least 22,000 expressed genes. Frequency ranged from low copy number
      (2-5, 68.8%) to highly abundant transcripts (100-->1,200; 1%). Quantitative
      reverse transcription-PCR for selected transcripts indicated high correlation
      with tag frequency. Computational analysis compared this set with known maize
      transcripts and other root transcriptome models. Among the 14,850 tags, 7,010
      (47%) were found for which no maize cDNA or gene model existed. Comparing the
      maize root transcriptome with that in other plants indicated that highly
      expressed transcripts differed substantially; less than 5% of the most abundant
      transcripts were shared between maize and Arabidopsis (Arabidopsis thaliana).
      Transcript categories highlight functions of the maize root tip. Significant
      variation in abundance characterizes transcripts derived from isoforms of
      individual enzymes in biochemical pathways.

PMID- 15965025
TI  - Isolation, characterization, and cloning of {alpha}-L-Arabinofuranosidase
      expressed during fruit ripening of Japanese pear.
AB  - alpha-L-Arabinofuranosidase (alpha-L-arafase) was purified from fruit of Japanese
      pear (Pyrus pyrifolia). The enzyme solubilized from the cell wall by NaCl and
      Triton X-100 had the homogeneity of a single 62-kD polypeptide on SDS-PAGE after
      purification through the steps of hydroxyapatite, anion-exchange chromatography,
      and size-exclusion chromatography. A related cDNA clone was isolated (PpARF2).
      The transcript and related protein were detected solely in the ripening fruit
      corresponding to the increase of alpha-L-arafase activity. Transcripts of PpARF2
      were not detected in buds, leaves, roots, or shoots of the Japanese pear. The
      deduced amino acid sequences of PpARF2 had low identity with those of other
      plants or bacteria. This alpha-L-arafase belonged to glycoside hydrolase family
      3, which includes some beta-xylosidases. The purified enzyme hydrolyzed mainly p
      nitrophenyl alpha-L-arabinofuranoside and also reacted bifunctionally with p
      nitrophenyl beta-d-xylopyranoside. However, it released only arabinose from
      native cell wall polysaccharides prepared from Japanese pear and from sugar beet
      arabinan. The enzyme did not release xylose from arabinoxylan and xylan. The only
      activity of the alpha-L-arafase presented here was hydrolyzing the arabinosyl
      residue from native polysaccharides, whereas it showed bifunctional activity
      against artificial substrates. According to the expression pattern and properties
      of the enzyme, it is a new member of the glycoside hydrolase family 3 isolated
      from fruit, and it may be responsible for modification of the cell wall
      architecture during fruit softening.

PMID- 15965026
TI  - Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van
      Buchem disease.
AB  - Mutations in distant regulatory elements can have a negative impact on human
      development and health, yet because of the difficulty of detecting these critical
      sequences, we predominantly focus on coding sequences for diagnostic purposes. We
      have undertaken a comparative sequence-based approach to characterize a large
      noncoding region deleted in patients affected by Van Buchem (VB) disease, a
      severe sclerosing bone dysplasia. Using BAC recombination and transgenesis, we
      characterized the expression of human sclerostin (SOST) from normal (SOST(wt)) or
      Van Buchem (SOST(vbDelta) alleles. Only the SOST(wt) allele faithfully expressed
      high levels of human SOST in the adult bone and had an impact on bone metabolism,
      consistent with the model that the VB noncoding deletion removes a SOST-specific
      regulatory element. By exploiting cross-species sequence comparisons with in
      vitro and in vivo enhancer assays, we were able to identify a candidate enhancer
      element that drives human SOST expression in osteoblast-like cell lines in vitro
      and in the skeletal anlage of the embryonic day 14.5 (E14.5) mouse embryo, and
      discovered a novel function for sclerostin during limb development. Our approach
      represents a framework for characterizing distant regulatory elements associated
      with abnormal human phenotypes.

PMID- 15965028
TI  - The net of life: reconstructing the microbial phylogenetic network.
AB  - It has previously been suggested that the phylogeny of microbial species might be
      better described as a network containing vertical and horizontal gene transfer
      (HGT) events. Yet, all phylogenetic reconstructions so far have presented
      microbial trees rather than networks. Here, we present a first attempt to
      reconstruct such an evolutionary network, which we term the "net of life". We use
      available tree reconstruction methods to infer vertical inheritance, and use an
      ancestral state inference algorithm to map HGT events on the tree. We also
      describe a weighting scheme used to estimate the number of genes exchanged
      between pairs of organisms. We demonstrate that vertical inheritance constitutes
      the bulk of gene transfer on the tree of life. We term the bulk of horizontal
      gene flow between tree nodes as "vines", and demonstrate that multiple but mostly
      tiny vines interconnect the tree. Our results strongly suggest that the HGT
      network is a scale-free graph, a finding with important implications for genome
      evolution. We propose that genes might propagate extremely rapidly across
      microbial species through the HGT network, using certain organisms as hubs.

PMID- 15965027
TI  - Distribution and intensity of constraint in mammalian genomic sequence.
AB  - Comparisons of orthologous genomic DNA sequences can be used to characterize
      regions that have been subject to purifying selection and are enriched for
      functional elements. We here present the results of such an analysis on an
      alignment of sequences from 29 mammalian species. The alignment captures
      approximately 3.9 neutral substitutions per site and spans approximately 1.9 Mbp
      of the human genome. We identify constrained elements from 3 bp to over 1 kbp in
      length, covering approximately 5.5% of the human locus. Our estimate for the
      total amount of nonexonic constraint experienced by this locus is roughly twice
      that for exonic constraint. Constrained elements tend to cluster, and we identify
      large constrained regions that correspond well with known functional elements.
      While constraint density inversely correlates with mobile element density, we
      also show the presence of unambiguously constrained elements overlapping
      mammalian ancestral repeats. In addition, we describe a number of elements in
      this region that have undergone intense purifying selection throughout mammalian
      evolution, and we show that these important elements are more numerous than
      previously thought. These results were obtained with Genomic Evolutionary Rate
      Profiling (GERP), a statistically rigorous and biologically transparent framework
      for constrained element identification. GERP identifies regions at high
      resolution that exhibit nucleotide substitution deficits, and measures these
      deficits as "rejected substitutions". Rejected substitutions reflect the
      intensity of past purifying selection and are used to rank and characterize
      constrained elements. We anticipate that GERP and the types of analyses it
      facilitates will provide further insights and improved annotation for the human
      genome as mammalian genome sequence data become richer.

PMID- 15965029
TI  - On the probability that a novel variant is a disease-causing mutation.
AB  - When a novel variant is found in a patient and not in a group of controls, it
      becomes a candidate for the disease-causing mutation in that patient. At present,
      no sampling theory exists for assessing the probability that the novel SNP might
      actually be a neutral variant. We have developed a population genetics-based
      method for calculating a P-value for a mutation-detection effort. Our method can
      be applied to a heterozygous patient, a homozygous patient, with or without
      inbreeding, or to a patient who is a compound heterozygote. Additionally, the
      method can be used to calculate the probability of finding a neutral variant at
      frequencies that differ between a group of patients and a group of controls,
      given some length of sequence examined. This method accounts for the multiple
      testing that is inherent in identification of variants through sequencing, to be
      used in subsequent case-control analyses. We show, for example, that for complete
      resequencing of 10 kb, the probability of finding a neutral variant in a patient
      and not in 50 controls is about 15%. Thus, discovery of a variant in a patient
      and not in a group of controls is, on its own, very weak evidence of involvement
      with disease.

PMID- 15965030
TI  - Physicochemical constraint violation by missense substitutions mediates
      impairment of protein function and disease severity.
AB  - We find that the degree of impairment of protein function by missense variants is
      predictable by comparative sequence analysis alone. The applicable range of
      impairment is not confined to binary predictions that distinguish normal from
      deleterious variants, but extends continuously from mild to severe effects. The
      accuracy of predictions is strongly dependent on sequence variation and is
      highest when diverse orthologs are available. High predictive accuracy is
      achieved by quantification of the physicochemical characteristics in each
      position of the protein, based on observed evolutionary variation. The strong
      relationship between physicochemical characteristics of a missense variant and
      impairment of protein function extends to human disease. By using four diverse
      proteins for which sufficient comparative sequence data are available, we show
      that grades of disease, or likelihood of developing cancer, correlate strongly
      with physicochemical constraint violation by causative amino acid variants.

PMID- 15965032
TI  - Intervention models for the management of children with signs of pneumonia or
      malaria by community health workers.
AB  - A systematic review was conducted to categorize and describe Intervention Models
      involving community health workers (CHWs) that aim to improve case management of
      sick children at the household and community levels. The review focused on
      management of children with signs of malaria or pneumonia. Seven Intervention
      Models were identified, and classified according to: (1) the role of CHWs and
      families in assessment and treatment of children, (2) system of referral to the
      nearest health facility (verbal or facilitated), and (3) the location in the
      community of the drug stock. Standardization of terminology for Intervention
      Models using this or a similar classification could facilitate comparison and
      selection of models, including deciding how to modify programmes when policies
      change concerning first-line drugs, and setting priorities for further research.
      Of the seven models, that of CHW pneumonia case management (Model 6) has the
      strongest evidence for an impact on mortality. Pneumonia case management by CHWs
      is a child health intervention that warrants considerably more attention,
      particularly in Africa and South Asia.

PMID- 15965033
TI  - Formative research for hygiene promotion in Kyrgyzstan.
AB  - Formative research for hygiene promotion was used to gather data relating to
      hygiene practices in rural Kyrgyzstan. Some of the hand-washing and faeces
      disposal practices observed were sub-optimal from a public health perspective. In
      combination with the poverty, limited medical services and poor water supply
      infrastructure characteristic of the study area, it is likely that these factors
      increase the risk of diarrhoeal infections among Kyrgyz children. An association
      was found between increased rates of hand-washing following latrine use and
      ownership of a washstand. This offers some empirical support for the idea that
      promotion of hand-washing technologies can form a useful part of a hygiene
      promotion intervention. The process followed in conducting the formative research
      is outlined in some detail along with a discussion of some of its achievements
      and limitations.

PMID- 15965031
TI  - Punctuated duplication seeding events during the evolution of human chromosome
      2p11.
AB  - Primate genomic sequence comparisons are becoming increasingly useful for
      elucidating the evolutionary history and organization of our own genome. Such
      studies are particularly informative within human pericentromeric regions--areas
      of particularly rapid change in genomic structure. Here, we present a systematic
      analysis of the evolutionary history of one approximately 700-kb region of 2p11,
      including the first autosomal transition from pericentromeric sequence to higher
      order alpha-satellite DNA. We show that this region is composed of segmental
      duplications corresponding to 14 ancestral segments ranging in size from 4 kb to
      approximately 115 kb. These duplicons show 94%-98.5% sequence identity to their
      ancestral loci. Comparative FISH and phylogenetic analysis indicate that these
      duplicons are differentially distributed in human, chimpanzee, and gorilla
      genomes, whereas baboon has a single putative ancestral locus for all but one of
      the duplications. Our analysis supports a model where duplicative transposition
      events occurred during a narrow window of evolution after the separation of the
      human/ape lineage from the Old World monkeys (10-20 million years ago). Although
      dramatic secondary dispersal events occurred during the radiation of the human,
      chimpanzee, and gorilla lineages, duplicative transposition seeding events of new
      material to this particular pericentromeric region abruptly ceased after this
      time period. The multiplicity of initial duplicative transpositions prior to the
      separation of humans and great-apes suggests a punctuated model for the formation
      of highly duplicated pericentromeric regions within the human genome. The data
      further indicate that factors other than sequence are important determinants for
      such bursts of duplicative transposition from the euchromatin to pericentromeric
      regions.

PMID- 15965034
TI  - The cost-effectiveness of a competitive voucher scheme to reduce sexually
      transmitted infections in high-risk groups in Nicaragua.
AB  - Current evidence suggests that sexually transmitted infection (STI) interventions
      can be an effective means of human immunodeficiency virus (HIV) prevention in
      populations at an early stage of the epidemic. However, evidence as to their cost
      effectiveness when targeted at high-risk groups is lacking. This paper assesses
      the cost-effectiveness of a competitive voucher scheme in Managua, Nicaragua
      aimed at high-risk groups, who could redeem the vouchers in exchange for free STI
      testing and treatment, health education and condoms, compared with the status quo
      (no scheme). A provider perspective was adopted, defined as: the voucher agency
      and health care providers from the public, NGO and private sectors. The cost of
      the voucher scheme was estimated for a 1-year period (1999) from project accounts
      using the ingredients approach. Outcomes were monitored as part of ongoing
      project evaluation. Costs and outcomes in the absence of the scheme were modelled
      using project baseline data and reports, and relevant literature. The annual cost
      of providing comprehensive STI services through vouchers was US$62 495, compared
      with an estimated US$17 112 for regular service provision in the absence of the
      scheme. 4815 vouchers were distributed by the voucher scheme, 1543 patients were
      tested for STIs and 528 STIs were effectively cured in this period. In the
      absence of the scheme, only an estimated 85 cases would have been cured from 1396
      consultations. The average cost of the voucher scheme per patient treated was
      US$41 and US$118 per STI effectively cured, compared with US$12 per patient
      treated and US$200 per STI cured in its absence. The incremental cost of curing
      an STI through the voucher scheme, compared with the status quo, was US$103. A
      voucher scheme offers an effective and efficient means of targeting and
      effectively curing STIs in high-risk groups, as well as encouraging quality care
      practices.

PMID- 15965035
TI  - Health care-seeking behaviour and out-of-pocket payments in Tbilisi, Georgia.
AB  - Based on a household survey conducted in Tbilisi, Georgia, in 2000, this paper
      examines current patterns of health care-seeking behaviour and the extent of out
      of-pocket payments. Results show that health care services are a financial burden
      and that private (out-of-pocket) payment creates financial barriers to accessing
      health services. Members of the poorest households are less likely to seek care
      than people from more affluent households, and devote a higher share of household
      monthly expenditure to health care. Households have adopted various strategies to
      overcome these financial barriers, but the strategies are likely to contribute to
      both declining economic status and worsening health outcomes. The paper provides
      an evidence base to help direct future policy reform in Georgia. Government needs
      to: (1) prioritize public financing of services for the poor, in particular
      through amending the Basic Benefit Package so that it better reflects the needs
      of the poor; (2) promote the quality and utilization of primary care services;
      (3) address the issue of rational drug use; and (4) consider mobilizing out-of
      pocket payments on a pre-paid basis through formal or community-based risk
      pooling schemes.

PMID- 15965036
TI  - Costs and revenue of health care in a rural Zimbabwean district.
AB  - The District Health Executive of Tsholotsho district in south-west Zimbabwe
      conducted a health care cost study for financial year 1997-98. The study's main
      purpose was to generate data on the cost of health care of a relatively high
      standard, in a context of decentralization of health services and increasing
      importance of local cost-recovery arrangements. The methodology was based on a
      combination of step-down cost accounting and detailed observation of resource use
      at the point of service. The study is original in that it presents cost data for
      almost all of the health care services provided at district level. The total
      annualized cost of the district public health services in Tsholotsho amounted to
      US$10 per capita, which is similar to the World Bank's Better Health in Africa
      study (1994) but higher than in comparable studies in other countries of the
      region. This can be explained by the higher standards of care and of living in
      Zimbabwe at the time of the study. About 60% of the costs were for the district
      hospital, while the different first-line health care facilities (health centres
      and rural hospitals together) absorbed 40%. Some 54% of total costs for the
      district were for salaries, 20% for drugs, 11% for equipment and buildings
      (including depreciation) and 15% for other costs. The study also looked into the
      revenue available at district level: the main source of revenue (85%) was from
      the Ministry of Health. The potential for cost recovery was hardly exploited and
      revenue from user fees was negligible. The study results further question the
      efficiency and relevance of maintaining rural hospitals at the current level of
      capacity, confirm the soundness of a two-tiered district health system based on a
      rational referral system, and make a clear case for the management of the
      different elements of the budget at the decentralized district level. The study
      shows that it is possible to deliver district health care of a reasonable quality
      at a cost that is by no means exorbitant, albeit unfortunately not yet within
      reach of many sub-Saharan African countries today.

PMID- 15965037
TI  - Cost valuation in resource-poor settings.
AB  - Methods of cost-effectiveness analysis (CEA) have largely been developed for
      application in Western country settings. Little attention has been paid to the
      methodological issues in cost valuation in resource-poor settings, where failing
      exchange rates and severe market distortions require further clarifications of
      appropriate valuation methods. This paper links insights from social cost-benefit
      analysis with the current CEA guidelines to develop a more apt approach to cost
      valuation in resource-poor settings.

PMID- 15965038
TI  - 10 best resources for...measuring population health.

PMID- 15965040
TI  - Mitochondria-based model for fetal origin of adult disease and insulin
      resistance.
AB  - Insulin resistance has been recognized as the fundamental underlying metabolic
      defect in the pathogenesis of metabolic syndrome, a clustering of cardiovascular
      risk factors such as diabetes, hypertension, dyslipidemia, and obesity. Recent
      studies established that mitochondrial dysfunction is involved in insulin
      resistance in general and fetal origin of this state in particular. Because genes
      are the fundamental molecular basis of inheritance--and thus the cornerstones of
      evolution--a model explaining insulin resistance is based at the gene level at
      best. Since a certain mtDNA polymorphism, 16189T>C, is associated with insulin
      resistance, mtDNA has to be a basic component of the gene-based model. We
      developed a mitochondria-based model that explains insulin resistance in terms of
      quantitative and qualitative change of the mitochondrion and its DNA. This model
      can accommodate several important hypotheses, such as thrifty genotype
      hypothesis, thrifty phenotype hypothesis, fetal insulin hypothesis, contribution
      of metabolic imprinting by epigenetic changes, and many other features associated
      with insulin resistance. We will discuss mechanisms that indicate why the
      perturbed initial condition of mitochondrial function should lead to the reduced
      insulin sensitivity.

PMID- 15965041
TI  - Evolutional analysis in determining pathogenic versus nonpathogenic mutations of
      ATPase 6 in human mitochondriopathy.
AB  - Because mitochondrial ATPase 6 plays an important role in ATP synthesis,
      mutations affecting ATPase 6 can undoubtedly cause human diseases. In contrast,
      the ATPase 6 gene is known to be a fast-evolving gene and has generated enough
      polymorphisms to allow identity investigation for forensic casework. To
      investigate these seemingly opposite views, we analyzed amino acid sequences of
      ATPase 6 in at least 1,266 humans, 102 mammals, and 213 vertebrates. The result
      showed that the amino acids of human ATPase 6 could be divided into the following
      four groups. Amino acid residue 192 (affected by alteration at nt 9101) and 79
      other residues were variable, and therefore substitutions of these residues would
      not be pathogenic. Amino acid residue 156 (affected by alteration at nt 8993) and
      93 other residues were conserved in Homo sapiens, but not in Mammalia. Therefore,
      they were potentially pathogenic if altered. Function studies would be necessary
      to confirm their role in pathogenesis. Amino acid residue 217 (affected by
      alteration at nt 9176) and 9 other residues were conserved across all species,
      including S. cerevisiae and E. coli. Mutations involving these residues would be
      pathogenic, some of which might even be life threatening. The remainder (42
      residues) were conserved in Mammalia, but not in yeast and E. coli. They were
      probably pathogenic if mutated. The classification proposed in this study may,
      therefore, provide an algorithm for a diagnostic approach when a newly identified
      change of ATPase 6 is suspected for human mitochondriopathy.

PMID- 15965042
TI  - Restoration of mitochondrial function in cells with complex I deficiency.
AB  - The mammalian mitochondrial NADH dehydrogenase (complex I) is the major entry
      point for the electron transport chain. It is the largest and most complicated
      respiratory complex consisting of at least 46 subunits, 7 of which are encoded by
      mitochondrial DNA (mtDNA). Deficiency in complex I function has been associated
      with various human diseases including neurodegenerative diseases and the aging
      process. To explore ways to restore mitochondrial function in complex I-deficient
      cells, various cell models with mutations in genes encoding subunits for complex
      I have been established. In this paper, we discuss various approaches to recover
      mitochondrial activity, the complex I activity in particular, in cultured cells.

PMID- 15965043
TI  - Hearing loss in mitochondrial disorders.
AB  - Hearing loss is a common clinical feature in mitochondria-syndrome disorders. The
      underlining molecular etiology of hearing loss has not been fully investigated.
      In this study, 83 patients with mitochondrial syndromic hearing loss were
      evaluated clinically and their blood and tissue samples were examined
      molecularly. Using modified Walker's criteria, 31, 31, 14, and 7 patients had
      been classified as having definite, probable, possible, and unlikely diagnosis of
      mitochondrial disease, respectively. Deleterious mtDNA point mutations and/or
      abnormal mtDNA content or multiple deletions were identified in 20 patients with
      definite diagnosis and 2 patients with probable diagnosis. In addition to known,
      undisputed pathogenic mutations, several novel mutations believed to be
      clinically significant were found. Furthermore, abnormal mtDNA content and mtDNA
      deletions were found in some of the cases. Evaluation of clinical and diagnostic
      features associated with hearing loss revealed that cardiomyopathy, lactic
      acidosis, deficient respiratory chain enzyme complex activities, histochemical
      and ultrastructural abnormalities in mitochondria, and abnormal brain imaging
      results occurred significantly more frequently in patients with mtDNA alterations
      than in those without. This study revealed that the majority of the mtDNA defects
      in patients with mitochondrial syndromic hearing loss affect the overall
      mitochondrial gene expression.

PMID- 15965044
TI  - Brain single photon emission computed tomography in patients with A3243G mutation
      in mitochondrial DNA tRNA.
AB  - Brain single photon emission computed tomography (SPECT) studies were conducted
      in three patients with A3243G mutation of the mitochondrial (mt) DNA tRNA. All
      were born to mothers suffering from chronic progressive external ophthalmoplegia
      (CPEO) with the same A3243G point mutation of the mtDNA tRNA. The first case
      manifested clinically with MELAS, the second case manifested with CPEO, and third
      case was characterized by recurrent migraine-like headache, tremor, and epilepsy.
      Brain SPECT of all patients, regardless of whether they had or had not suffered
      from stroke-like episodes, showed multiple areas of asymmetrical decreased
      perfusion, particularly in the posterior and lateral head regions, especially the
      temporal lobes. Crossed-cerebellar diaschisis may occur. Conventional brain
      magnetic resonance images failed to show some of the lesions. Decreased regional
      cerebral blood flow, rather than previously proposed hyperemia, is likely to be
      the cause. We conclude that mitochondrial vasculopathy with regional cerebral
      hypoperfusion may be seen on brain SPECT in patients with mitochondrial disorders
      and A3243G mutations, regardless of whether they have or have not suffered from
      stroke-like episodes.

PMID- 15965045
TI  - Upregulation of matrix metalloproteinase 1 and disruption of mitochondrial
      network in skin fibroblasts of patients with MERRF syndrome.
AB  - By using cDNA microarray and RT-PCR techniques, we investigated the genome-wide
      alteration of gene expression in skin fibroblasts from patients with myoclonic
      epilepsy and ragged-red fibers (MERRF) syndrome. By screening for the genes with
      altered levels of expression, we first discovered that matrix metalloproteinase 1
      (MMP1) was highly induced in the primary culture of skin fibroblasts of a female
      patient in a four-generation family with MERRF syndrome. This phenomenon was
      confirmed in skin fibroblasts from three other MERRF patients harboring about 85%
      of mtDNA with A8344G mutation. A further study revealed that the expression of
      MMP1 could be further induced by treatment of the skin fibroblasts with 200
      microM hydrogen peroxide (H2O2) and inhibited by 1 mM N-acetylcysteine. Moreover,
      the intracellular level of H2O2 in skin fibroblasts of the female MERRF patient
      was higher than those of the asymptomatic family members and age-matched healthy
      controls. These findings imply that the increase in the expression of MMP1 may
      represent one of the responses to the increased oxidative stress in the skin
      fibroblasts of MERRF patients. We suggest that in affected tissues the oxidative
      stress-elicited overexpression of MMP1, and probably other matrix
      metalloproteinases involved in cytoskeleton remodeling, may play an important
      role in the pathogenesis and progression of mitochondrial encephalomyopathies
      such as MERRF syndrome.

PMID- 15965046
TI  - Increased oxidative damage with altered antioxidative status in type 2 diabetic
      patients harboring the 16189 T to C variant of mitochondrial DNA.
AB  - A transition of T to C at nucleotide position 16189 in mitochondrial DNA (mtDNA)
      has attracted biomedical researchers for its probable correlation with the
      development of diabetes mellitus in adult life. In diabetes, persistent
      hyperglycemia may cause high production of free radicals. Reactive oxygen species
      are thought to play a role in a variety of physiologic and pathophysiologic
      processes in which increased oxidative stress may play an important role in
      disease mechanisms. The aim of the present study was to clarify the degree of
      oxidative damage and plasma antioxidant status in diabetic patients and to see
      the potential influence of the 16189 variant of mtDNA on the oxidative status in
      these patients. An indicative parameter of lipid peroxidation, malondialdehyde
      (MDA), and total free thiols were measured from plasma samples of 165 type 2
      diabetic patients with or without this variant and 168 normal subjects. Here we
      report an increase in the plasma levels of MDA and total thiols in type 2
      diabetic patients compared with control subjects. The levels of plasma thiols in
      diabetic patients with the 16189 variant of mtDNA were not different from those
      in controls. These results suggest an increase in the oxidative damage and a
      compensatory higher antioxidative status in patients with type 2 diabetes.
      Harboring the 16189 mtDNA variant may impair the ability of a cell to respond
      properly to oxidative stress and oxidative damage.

PMID- 15965047
TI  - Alteration of the copy number of mitochondrial DNA in leukocytes of patients with
      hyperlipidemia.
AB  - Lipid metabolism in leukocytes may be disturbed by mitochondrial dysfunction
      caused by depletion of mitochondrial DNA (mtDNA) in response to an increase of
      oxidative stress in blood circulation. It is possible that alteration in mtDNA
      copy number of the leukocyte is involved in the impairment of the scavenging of
      oxidatively modified plasma proteins such as oxidized low-density lipoprotein
      (oxLDL). To test this hypothesis, we recruited 91 healthy subjects and 63
      patients with hyperlipidemia (LDL >130 mg/dL) for this study. The copy number of
      mtDNA in the leukocyte and the titer of oxLDL IgG autoantibody (oLAB) were
      determined as indices of the oxidative stress response of immune cells. The
      results revealed a significant higher level of plasma oxLDL, lower titer of oLAB,
      and decreased copy number of mtDNA in patients with hyperlipidemia (P <0.05). In
      the analysis of partial correlations under age control, we found that an increase
      in the copy number of mtDNA was positively correlated with an increase in the
      level of oLAB (P <0.005, r = 0.3002) and a decrease in the oxLDL level (P <0.05,
      r = -0.2654) in healthy subjects but not in patients. Based on the results
      obtained from this case-control study, we conclude that the increase of mtDNA
      copy number might provide the leukocyte an increased capability of scavenging
      oxLDL, possibly by enhanced generation of oLAB in healthy subjects, but not in
      hyperlipidemic patients who had lower mtDNA copy numbers in their leukocytes.
      Taken together, these findings suggest that an alteration of mtDNA copy number in
      the leukocyte may be one of the risk factors for hyperlipidemia.

PMID- 15965048
TI  - A new noninvasive test to detect mitochondrial dysfunction of skeletal muscles in
      progressive supranuclear palsy.
AB  - We present usage of technetium-99m methoxyisobutyl isonitrile (99mTc-sestamibi)
      single photon emission computed tomography (SPECT) as a novel noninvasive method
      to evaluate muscular mitochondrial function in patients with progressive
      supranuclear palsy (PSP). 99mTc-sestamibi SPECT revealed a statistically
      significant decrease in radionucleotide uptake in the quadriceps in PSP patients
      as compared with other neurodegenerative parkinsonism (P < 0.05) or control group
      (P < 0.05). This study demonstrates a remarkable deficit of skeletal muscle
      bioenergetics in patients with PSP. Our findings suggest a distinctive role of
      mitochondrial dysfunction in the pathogenesis of PSP. Furthermore, 99mTc
      sestamibi SPECT provides a relatively simple, inexpensive, and noninvasive
      modality in further assessment of mitochondrial function and bioenergetic
      features in various muscular disorders.

PMID- 15965049
TI  - High prevalence of the COII/tRNA(Lys) intergenic 9-bp deletion in mitochondrial
      DNA of Taiwanese patients with MELAS or MERRF syndrome.
AB  - The COII/tRNA(Lys) intergenic 9-bp deletion (MIC9D) of mitochondrial DNA (mtDNA)
      has been established as a genetic polymorphism for Asian-Pacific populations. We
      investigated whether this small mtDNA deletion is co-transmitted with human
      diseases such as mitochondrial encephalomyopathy with lactic acidosis and stroke
      like episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF)
      syndromes. Forty unrelated Taiwanese families, including 12 families with MERRF
      and A8344G mtDNA mutation and 28 families with MELAS and A3243G mutation of
      mtDNA, respectively, were recruited in this study. In addition, 199 healthy
      subjects were recruited as control. We found that the frequency of occurrence of
      mtDNA with the MIC9D polymorphism in healthy subjects was 21% (41/199). However,
      the incidence of the MIC9D polymorphism was 67% (8/12) among the probands of all
      the families with MERRF syndrome (P = 0.001; OR = 8) and 39% (11/28) among the
      probands of the families with MELAS syndrome (P = 0.038; OR = 2). This finding
      indicates that the frequency of occurrence of mtDNA with the MIC9D polymorphism
      in patients with MERRF or MELAS syndrome is higher than that of healthy subjects.
      The prevalence of mitochondrial encephalomyopathies in relation to the MIC9D
      polymorphism of mtDNA in Taiwanese population is discussed.

PMID- 15965050
TI  - Analysis of proteome bound to D-loop region of mitochondrial DNA by DNA-linked
      affinity chromatography and reverse-phase liquid chromatography/tandem mass
      spectrometry.
AB  - Mitochondrial dysfunction has been suggested as a causal factor for insulin
      resistance and diabetes. Previously we have shown a decrease of mitochondrial DNA
      (mtDNA) content in tissues of diabetic patients. The mitochondrial proteins,
      which regulate the mitochondrial biogensis, including transcription and
      replication of mtDNA, are encoded by nuclear DNA. Despite the potential function
      of the proteins bound to the D-loop region of mtDNA in regulating mtDNA
      transcription/replication, only a few proteins are known to bind the D-loop
      region of mtDNA. The functional association of these known proteins with insulin
      resistance is weak. In this study, we applied proteomic analysis to identify a
      group of proteins (proteome) that physically bind to D-loop DNA of mtDNA. We
      amplified D-loop DNA (1.1 kb) by PCR and conjugated the PCR fragments to CNBr
      activated sepharose. Mitochondria fractions were isolated by both differential
      centrifugation and Optiprep-gradient ultracentrifugation. The D-loop DNA binding
      proteome fractions were enriched via this affinity chromatography and analyzed by
      SDS-PAGE. The proteins on the gel were transferred onto PVDF membrane and the
      peptide sequences of each band were subsequently analyzed by capillary reverse
      phase liquid chromatography/tandem mass spectrometry (RPLC/MS/MS). We identified
      many D-loop DNA binding proteins, including mitochondrial transcription factor A
      (mtTFA, Tfam) and mitochondrial single-stranded DNA binding protein (mtSSBP)
      which were known to bind to mtDNA. We also report the possibility of novel D-loop
      binding proteins such as histone family proteins and high-mobility group
      proteins.

PMID- 15965051
TI  - Mitochondrial transcription factor A in the maintenance of mitochondrial DNA:
      overview of its multiple roles.
AB  - Mitochondria have their own genome, which is essential for proper oxidative
      phosphorylation needed for a large part of ATP production in a cell. Although
      mitochondrial DNA-less (rho0) cells can survive under special conditions, the
      integrity of the mitochondrial genome is critical for survival of multicellular
      organisms. Mitochondrial transcription factor A (TFAM), originally cloned as
      transcription factor, is essential for the maintenance of mtDNA. Recently, it has
      become known that TFAM plays critical roles in multiple aspects to maintain the
      integrity of mitochondrial DNA: transcription, replication, nucleoid formation,
      damage sensing, and DNA repair. The effects of TFAM in these aspects are
      intimately related to each other and to function as a whole for the purpose of
      maintenance of mtDNA.

PMID- 15965052
TI  - Mitochondrial genome instability and mtDNA depletion in human cancers.
AB  - An increase in the rate of glycolysis is one of the metabolic alterations in most
      cancer cells. However, the role of alterations in mitochondrial function and
      mitochondrial DNA (mtDNA) in carcinogenesis still remains unclear. In this study,
      we analyzed the nucleotide sequence of the D-loop and the copy number of mtDNA in
      54 hepatocellular carcinomas (HCCs), 31 gastric, 31 lung, and 25 colorectal
      cancers as well as their corresponding non-tumorous tissues. The results revealed
      that 42.6% (23/54) of the HCCs, 51.6% (16/31) of the gastric cancers, 22.6%
      (7/31) of the lung cancers, and 40.0% (10/25) of the colorectal cancers harbored
      mutation(s) in the D-loop of mtDNA. The mtDNA mutations in 43.5% (10/23) of the
      HCCs, 62.5% (10/16) of the gastric cancers, 57.1% (4/7) of the lung cancers, and
      90.0% (9/10) of the colorectal cancers were changes in the mononucleotide or
      dinucleotide repeats, deletions, or multiple insertions. Moreover, we found that
      there is a significant decrease in mtDNA copy number in 57.4% (31/54) of the
      HCCs, 54.8% (17/31) of the gastric cancers, 22.6% (7/31) of the lung cancers, and
      28.0% (7/25) of the colorectal cancers compared with the corresponding non
      tumorous tissues. It is noteworthy that the incidence of somatic mutations in the
      D-loop of mtDNA in the cancers of later stages was higher than that of the early
      stage cancers. Taken together, our findings suggest that instability in the D
      loop region of mtDNA, together with the decrease in mtDNA copy number, is
      involved in the carcinogenesis of human cancers.

PMID- 15965053
TI  - Frequent occurrence of mitochondrial microsatellite instability in the D-loop
      region of human cancers.
AB  - We analyzed the occurrence of mitochondrial microsatellite instability (mtMSI) in
      262 pairs of female cancer tissues with the matched normal controls. mtMSI was
      detected in only 4 of 12 microsatellites found in the mitochondrial genome (3 in
      the D-loop and 1 in the 12S rRNA gene). Interestingly, 95.6% (87/91) of mtMSI was
      detected in the D-loop, namely, at nucleotide positions 303-315, 514-523, and
      16184-16193. This demonstrates that the D-loop is a hotspot for mtMSI. Different
      incidences of mtMSI at these three microsatellites were found in the four cancer
      types (including cervical, endometrial, ovarian, and breast). Together with those
      mtMSI reported in other studies, the differential occurrence of mtMSI at each of
      the markers in the D-loop region was observed, indicating that the extent of
      mtMSI varies from one cancer to another. Although the mechanisms of generation
      and functional impact of mtMSI are still not clear, the high incidence of mtMSI
      in the D-loop and its broad distribution in human cancers render it a potential
      marker for cancer detection.

PMID- 15965054
TI  - Analysis of heteroplasmy in hypervariable region II of mitochondrial DNA in
      maternally related individuals.
AB  - Mitochondrial DNA sequences have been widely employed for identity investigation.
      However, the presence of a heteroplasmic site may complicate sequence analysis
      for forensic purposes when two samples are compared. To study this potential
      problem, we analyzed the hypervariable region of the displacement loop in five
      maternally related individuals, that is, grandmother, mother, one son, and two
      daughters. The results showed that three of them had a heteroplasmic site at
      nucleotide position (np) 204, located in the hypervariable region II. By using
      Bayesian inference to assess the significance of the mother-offspring pairs, a
      likelihood ratio of 1.78 x 10(5) was obtained. Therefore, Bayesian inference does
      not place the prior odds into the context of the two different likelihood ratios
      derived from the DNA evidence. On the other hand, the chromatogram of the
      denaturing high-performance liquid chromatography system proved that the single
      peak in a sequencing chromatogram at np 204 was, in fact, heteroplasmic in
      nature. This study demonstrated that heteroplasmy is a common occurrence in
      tissue from normal individuals and should be taken into account in forensic
      investigation when samples appear to differ at a single nucleotide position by
      direct sequencing.

PMID- 15965055
TI  - Deleted mitochondrial DNA in human luteinized granulosa cells.
AB  - The rearrangement of mitochondrial DNA in luteinized granulosa cells was
      determined in order to evaluate the fertilization capacity of oocytes and the
      development of embryos. Multiple deletions of mtDNA were found in luteinized
      granulosa cells from in vitro fertilization (IVF) patients. The 4977-base pair
      (bp) deletion was the most frequent deletion found in human granulosa cells. No
      significant difference was noted between mtDNA deletions of granulosa cells based
      on the fertilization capacity of oocytes and the development of embryos. To
      determine the relationship of proportions of mtDNA rearrangements with the aging
      process, granulosa cells were grouped into three different cohorts according to
      maternal age: younger than 32 years, between 32 and 37 years, and older than 37
      years. No statistical correlation was noted between patient age and the frequency
      of occurrence of multiple mtDNA deletions. However, an increase in granulosa cell
      apoptosis was associated with an increase in mtDNA deletions. Accumulation of
      mtDNA deletions may contribute to mitochondrial dysfunction and impaired ATP
      production. We concluded that the accumulation of rearranged mtDNA in granulosa
      cells might not interfere with fertilization of human oocytes and further
      embryonic development; it was, however, associated with apoptosis processes.

PMID- 15965056
TI  - Identification of human-specific adaptation sites of ATP6.
AB  - Mitochondria play an essential role in forming ATP and generating heat. The
      proportion of these two depends on the coupling efficiency of electrochemical
      gradient to synthesize ATP. Therefore, an increased basal metabolic rate caused
      by partial uncoupling of the mitochondria can be balanced by a high caloric
      intake provided by a high-fat diet. The recent study by Mishmar et al. (Proc.
      Natl. Acad. Sci. USA 2003; 100: 171-176) suggested that ATP6 was the most
      variable gene among human mitochondrial DNAs and probably resulted from the
      adaptation of Homo sapiens to the colder climate during the migration out of
      Africa. According to this adaptation theory, the ATP6 of Homo sapiens (omnivorous
      animals consuming fat-containing diet) should be significantly different from
      that of other primates for permitting human adaptation to the dietary conditions.
      On the basis of this rationale, we analyzed ATP6 sequences of 136 unrelated
      Taiwanese subjects, which then were compared with 1,130 reported sequences. The
      obtained human consensus from 1,266 individuals was compared with that derived
      from 42 species of primates other than human. The alignment showed that human
      ATP6 harbored 80 variable residues, among which 25 amino acids were conserved in
      other primates, suggesting that adaptation constraints operating at the amino
      acid level results in the species-specific difference of ATP6. Therefore, these
      25 amino acids are probably the human-specific adaptation residues of ATP6.

PMID- 15965057
TI  - Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA
      mutations in mouse ovaries.
AB  - Superovulation by injection of exogenous gonadotropin is the elementary method to
      produce in vivo-derived embryos for embryo transfer in women. Increased oocyte
      aneuploidy, embryo mortality, fetal growth retardation, and congenital
      abnormalities have been studied at higher-dose stimulations. Ovarian and oocyte
      biological aging possibly may have adverse implications for human oocyte
      competence with repeated hyperstimulation. In this study, we found that reduced
      competence for the human oocyte has been associated with degenerative embryo
      upsurge during embryo culture and failure to develop into the blastocyst stage in
      the three, four, five, and six stimulation cycles. On the other hand, the numbers
      of ovulated oocytes were decreased in the groups with more ovarian stimulation.
      More aggregated mitochondria were found in the cytoplasm of the repetitively
      stimulated embryos. Higher amounts of oxidative damage including 8-OH-dG,
      lipoperoxides, and carbonyl proteins were also revealed in the ovaries with more
      cycle numbers of ovarian stimulation. Higher proportions of mtDNA mutations were
      also found. The detected molecular size of the mutated band was approximately 675
      bp. Increased amounts of carbonyl proteins were also revealed after repeated
      stimulation. An understanding of the relationship between oocyte competence and
      ovarian responses to stimulation in the mouse may provide insights into the
      origin of oocyte defects and the biology of ooplasmic aging that could be of
      clinical relevance in the diagnosis and treatment of human infertility.

PMID- 15965058
TI  - Calcium stimulates mitochondrial biogenesis in human granulosa cells.
AB  - Ovarian granulosa cells are known to play a key role in regulating ovarian
      physiology. Age increases apoptosis in follicular granulosa cells and
      subsequently decreases ovarian fecundity. The aging ovary also contains fewer
      follicles that possess fewer granulosa cells. The viability of follicular
      granulosa cells may be essential for development of the oocyte. Calcium ion plays
      an important role in a variety of biological processes, including gene
      expression, cell cycle regulation, and cell death. To study the ability of
      mitochondrial biogenesis in human granulosa cells, we determined the
      mitochondrial marker proteins, including the nuclear-encoded NADH-ubiquinone
      oxidoreductase alpha subunit 9 (NDUFA9) and mitochondrial-encoded COX I, after
      treatment of the cells with the calcium ionophore A23187. We showed that the
      expression of these mitochondrial marker proteins in human granulosa cells
      increased with changes in cytosolic Ca2+ using the ionophore A23187. Treatment of
      granulosa cells with 0.5 microM of A23187 for 120 h increased the levels of NDUFA
      9 and COX I subunit by up to 2.6- and 2.4-fold, respectively. Raising Ca2+ by
      exposing granulosa cells to 1 microM of A23187 for 48 h significantly increased
      mitochondrial transcription factor (mtTFA) gene expression by up to 2.9-fold. Our
      results indicate that the adaptive responses of granulosa cells to increased Ca2+
      may include upregulation of mitochondrial proteins and that mtTFA may be involved
      in such a mitochondrial biogenesis pathway.

PMID- 15965059
TI  - Dynamics of mitochondria and mitochondrial Ca2+ near the plasma membrane of PC12
      cells: a study by multimode microscopy.
AB  - The goal of this study is to examine whether there is a difference in the
      regulation of Ca2+ between mitochondria near the cell surface and mitochondria in
      the cytosol. Total internal reflection fluorescence and epifluorescence
      microscopy were used to monitor changes in the mitochondrial Ca2+ ([Ca2+]mt)
      between the mitochondria near the plasma membrane and those in the cytosol. The
      results show that [Ca2+]mt near the plasma membrane increased earlier and decayed
      slower after high K+ stimulation than average mitochondria in the cytosol. In
      addition, the changes in [Ca2+]mt in the mitochondria near the cell surface after
      a second stimulation were larger than those induced by the first stimulation. The
      results provide direct evidence to support the hypothesis that mitochondria in
      different subcellular localization show differential responses to the influx of
      extracellular Ca2+.

PMID- 15965060
TI  - Propofol specifically inhibits mitochondrial membrane potential but not complex I
      NADH dehydrogenase activity, thus reducing cellular ATP biosynthesis and
      migration of macrophages.
AB  - Propofol is a widely used intravenous anesthetic agent. Our previous study showed
      that a therapeutic concentration of propofol can modulate macrophage functions.
      Mitochondria play critical roles in the maintenance of macrophage activities.
      This study attempted to evaluate further the effects of mitochondria on the
      propofol-induced suppression of macrophage functions using mouse macrophage-like
      Raw 264.7 cells as the experimental model. Macrophages were exposed to a
      clinically relevant concentration of propofol for 1, 6, and 24 h. Analysis by the
      Trypan blue exclusion method revealed that propofol was not cytotoxic to
      macrophages. Exposure of macrophages to propofol did not affect mitochondrial
      NADH dehydrogenase activity of complex I. However, analysis of flow cytometry
      showed that propofol significantly decreased the mitochondrial membrane potential
      of macrophages. Cellular levels of ATP in macrophages were significantly reduced
      after propofol administration. In parallel with the dysfunction of mitochondria,
      the chemotactic analysis showed that exposure to propofol significantly inhibited
      the migration of macrophages. This study shows that a therapeutic concentration
      of propofol can specifically reduce the mitochondrial membrane potential, but
      there is no such effect on complex I NADH dehydrogenase activity. Modulation of
      the mitochondrial membrane potential may decrease the biosynthesis of cellular
      ATP and thus reduce the chemotactic activity of macrophages. This study provides
      in vitro data to validate mitochondrial dysfunction as a possible critical cause
      for propofol-induced immunosuppression of macrophage functions.

PMID- 15965061
TI  - Abnormal mitochondrial structure in human unfertilized oocytes and arrested
      embryos.
AB  - To clarify the relationship between mitochondria and embryo development, we
      collected human unfertilized oocytes, early embryos, and arrested embryos.
      Unfertilized oocytes and poor-quality embryos were collected, and the
      ultrastructure of mitochondria was determined by transmission electron
      micrography. Four criteria for determining the mitochondrial state were
      mitochondrial morphology, cristae shape, location, and number of mitochondria. In
      mature oocytes, mitochondria were rounded with arched cristae and a dense matrix
      and were distributed evenly in the ooplasm. In pronuclear zygotes, the size and
      shape of mitochondria were similar to those in mature oocytes; however,
      mitochondria appeared to migrate and concentrate around pronuclei. In this study,
      67% of examined unfertilized oocytes had fewer mitochondria in the cytoplasm. A
      decreased number of mitochondria located near the nucleus was also demonstrated
      in 60% of arrested embryos. Fewer differentiated cristae were determined in all
      three arrested blastocyst stages of embryos. The relative expressions of
      oxidative phosphorylation genes in oocytes and embryos were also determined.
      These data imply that inadequate redistribution of mitochondria, unsuccessful
      mitochondrial differentiation, or decreased mitochondrial transcription may
      result in poor oocyte fertilization and compromised embryo development.

PMID- 15965062
TI  - Oxidative damage and mitochondrial DNA mutations with endometriosis.
AB  - Endometriosis, a frequently encountered disease in gynecology, is a considerable
      threat to the physical, psychological, and social integrity of women. Moreover,
      up to 50% of infertile patients have this disease. The etiology and pathogenesis
      of this important disease are poorly understood; it is defined as an ectopic
      location for endometrium-like glandular epithelium and stroma outside of the
      uterine cavity. It still remains an open question as to what extent the
      peritoneal environment influences the establishment and/or progression of
      endometriosis. As a result of such stress, a sterile, inflammatory reaction with
      the secretion of growth factors, cytokines, and chemokines is generated, which is
      especially deleterious to successful reproduction. Significantly higher amounts
      of oxidative damage were detected in endometriotic lesions than in controlled
      normal endometrium, including mitochondrial DNA (mtDNA) rearrangement, 8-OH
      deoxyguanosine (8-OH-dG), and lipoperoxide contents. There were approximately
      sixfold increases in 8-OH-dG and lipoperoxides in chocolate cysts compared with
      normal endometrial tissues. A novel 5,335-bp deletion of mtDNA was identified in
      endometriotic tissue. According to these results, we propose that oxidative
      stress and mtDNA mutations might be anticipated in the initiation or progression
      of endometriosis. Only by understanding the mechanisms involved in the
      pathogenesis of endometriosis can we develop a basis for new diagnostic and
      therapeutic approaches.

PMID- 15965063
TI  - Neuroprotective role of coenzyme Q10 against dysfunction of mitochondrial
      respiratory chain at rostral ventrolateral medulla during fatal mevinphos
      intoxication in the rat.
AB  - We evaluated the functional changes in the mitochondrial respiratory chain at the
      rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic
      vasomotor tone, in an experimental model of fatal organophosphate poisoning using
      the insecticide mevinphos (Mev). We also investigated the neuroprotective role of
      coenzyme Q10 (CoQ10) in this process. Intravenous administration of Mev (1 mg/kg)
      in Sprague-Dawley rats maintained with propofol elicited an initial hypertension
      followed by hypotension, accompanied by bradycardia, with death ensuing within 10
      min. Enzyme assay revealed a significant depression of the activity of
      nicotinamide adenine dinucleotide cytochrome c reductase, succinate cytochrome c
      reductase, and cytochrome c oxidase in the RVLM during this fatal Mev
      intoxication. ATP production also underwent a significant decrease. Pretreatment
      by microinjection bilaterally of CoQ10 (4 microg) into the RVLM significantly
      prevented mortality, antagonized the cardiovascular suppression, and reversed the
      depressed mitochondrial respiratory enzyme activities, or reduced ATP production
      in the RVLM induced during Mev intoxication. Our results indicated that
      dysfunction of mitochondrial respiratory chain and energy production at the RVLM
      takes place during fatal Mev intoxication. We further demonstrated that CoQ10
      provides neuroprotection against Mev-induced cardiovascular depression and
      fatality through maintenance of activity of the key mitochondrial respiratory
      enzymes in the RVLM.

PMID- 15965064
TI  - Mitochondrial dysfunction and oxidative stress as determinants of cell
      death/survival in stroke.
AB  - Mitochondria are the powerhouse of the cell. Their primary physiological function
      is to generate ATP through oxidative phosphorylation via the electron transport
      chain. Reactive oxygen radicals generated from mitochondria have been implicated
      in acute brain injuries, like stroke and neurodegeneration. Recent studies have
      shown that mitochondrially formed oxidants are mediators of molecular signaling
      and have implicated mitochondria-dependent apoptosis involving pro- and
      antiapoptotic protein binding, the release of cytochrome c and Smac, the
      activation of downstream caspase-9 and -3, and the fragmentation of DNA.
      Oxidative stress and the redox state are also implicated in the survival
      signaling pathway that involves phosphatidylinositol 3-kinase (PI3-K)/Akt and
      downstream signaling molecular bindings like Bad/Bcl-X(L) and phosphorylated
      Bad/14-3-3. Genetically modified mice (SOD1, SOD2) or rats that overexpress or
      are deficient in superoxide dismutase have provided strong evidence in support of
      the role of mitochondrial dysfunction and oxidative stress as determinants of
      neuronal death/survival after stroke and neurodegeneration.

PMID- 15965065
TI  - Oxidative damage in mitochondrial DNA is not extensive.
AB  - Since 1988 several research groups have reported greater levels of oxidative
      damage in mitochondrial DNA than in nuclear DNA, while others have suggested that
      the greater damage in mtDNA might be due to artifactual oxidation. The popular
      theory that mtDNA is more heavily damaged in vivo than nDNA does not stand on
      firm ground. Using an improved GC-MS method and pure mtDNA, our analyses revealed
      that the damage level in mtDNA is not higher, and may be somewhat lower, than
      that in nDNA.

PMID- 15965066
TI  - Enhanced generation of mitochondrial reactive oxygen species in cybrids
      containing 4977-bp mitochondrial DNA deletion.
AB  - The poor bioenergetic state in mitochondria containing mtDNA with the 4977-bp
      deletion has been well documented. However, information on mitochondrial reactive
      oxygen species (ROS) generation at rest or under intense oxidative stress in
      mitochondria lacking the 4977-bp mtDNA fragment inside intact living cells was
      insufficient. We used cybrids containing truncated mtDNA lacking the 4977-bp
      fragment and measured ROS levels inside cybrids by fluorescence probe, 2',7'
      dichlorodihydrofluorescein (DCF), and confocal microscopy. Mitochondrial ROS at
      resting state was slightly higher in cybrids containing 4977-bp deletion mtDNA as
      compared to cybrids without mtDNA defects. For intense oxidative stress
      treatment, cybrids were treated with 5 mM H2O2 for 10 min. Consecutive DCF images
      were acquired after H2O2 had been washed away. Progressive increase of DCF
      signals, especially in the mitochondrial area, was observed in cybrids containing
      4977-bp deletion mtDNA, even long after the brief, intense H2O2 treatment. This
      result suggests that a feed-forward, self-accelerating vicious cycle of
      mitochondrial ROS production could be initiated in cybrids containing 4977-bp
      deletion fragment mitochondria after brief, intense H2O2 treatment. This
      mechanism may play an important role in the pathophysiology of the disease
      process caused by mitochondria containing mtDNA with the 4977-bp deletion.

PMID- 15965067
TI  - S-nitrosoglutathione and hypoxia-inducible factor-1 confer chemoresistance
      against carbamoylating cytotoxicity of BCNU in rat C6 glioma cells.
AB  - BCNU (1,3-bis[2-chloroethyl]-1-nitrosourea) is the mainstay in glioblastoma
      multiform chemotherapy with only minimal effects. BCNU may kill tumor cells via
      carbamoylating cytotoxicity, which irreversibly inhibits glutathione reductase
      with resultant accumulation of oxidized form of glutathione causing oxidative
      stress. S-nitrosoglutathione (GSNO) is a product of glutathione and nitric oxide
      interaction. We report that GSNO formation may underlie carbamoylating
      chemoresistance mediated by activation of inducible nitric oxide synthase.
      Transactivation of hypoxia-inducible factor-1 (HIF-1)-responsive genes reduces
      oxidative stress caused by glutathione depletion. We also noted that
      preconditioning of C6 glioma cells to induce HIF-1 and its downstream genes
      confers chemoresistance against carbamoylating cytotoxicity of BCNU.

PMID- 15965068
TI  - Celecoxib induces heme-oxygenase expression in glomerular mesangial cells.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics.
      They inhibit cyclooxygenases (COX), preventing the formation of prostaglandins,
      including prostacyclin and thromboxane. A serious side effect of COX-1 and COX-2
      inhibitors is renal damage. To investigate the molecular basis of the renal
      injury, we evaluated the expression of the stress marker, heme oxygenase-1 (HO
      1), in celecoxib-stimulated mesangial cells. We report here that a COX-2
      selective NSAID, celecoxib, induced a concentration- and time-dependent increase
      of HO-1 expression in glomerular mesangial cells. Celecoxib-induced HO-1 protein
      expression was inhibited by actinomycin D and cycloheximide, suggesting that de
      novo transcription and translation are required in this process. N
      acetylcysteine, a free radical scavenger, strongly decreased HO-1 expression,
      suggesting the involvement of reactive oxygen species (ROS). Celecoxib-induced HO
      1 expression was attenuated by pretreatment of the cells with SP 600125 (a
      specific JNK inhibitor), but not SB 203580 (a specific p38 MAPK inhibitor), or PD
      98059 (a specific MEK inhibitor). Consistently, celecoxib activated c-Jun N
      terminal kinase (JNK) as demonstrated by kinase assays and by increasing
      phosphorylation of this kinase. N-acetylcysteine reduced the stimulatory effect
      of celecoxib on stress kinase activities, suggesting an involvement of JNK in HO
      1 expression. On the other hand, LY 294002, a phosphatidylinositol 3-kinase (PI
      3K)-specific inhibitor, prevented the enhancement of HO-1 expression. This effect
      was correlated with inhibition of the phosphorylation of the PDK-1 downstream
      substrate Akt/protein kinase B (PKB). In conclusion, our data suggest that
      celecoxib-induced HO-1 expression in glomerular mesangial cells may be mediated
      by ROS via the JNK-PI-3K cascade.

PMID- 15965069
TI  - Oxidative stress-induced depolymerization of microtubules and alteration of
      mitochondrial mass in human cells.
AB  - Mitochondrial biogenesis is a biological process that has been intensively
      studied over the past few years. However, the detailed molecular mechanism
      underlying this increase in mitochondria remains unclear. To investigate the
      mechanism of such a mitochondrial proliferation, we examined alterations in
      mitochondria of human osteosarcoma 143B cells that had been treated with 100 to
      500 microM hydrogen peroxide (H2O2) for 48 h. The results showed that
      mitochondrial mass of the cell was increased with the increase of the
      concentration of H2O2. On the other hand, by using real-time PCR techniques, we
      observed the changes of mitochondrial DNA (mtDNA) content in the cells exposed to
      oxidative stress. The copy number of mtDNA was increased by treatment with a low
      dose of H2O2 but was drastically decreased after treatment with H2O2 higher than
      300 microM. Transmission electron microscopic images revealed that mitochondria
      were abnormally proliferated in cells exposed to oxidative stress. Moreover, we
      found that the percentage of 143B cells arrested at the G2/M phase increased upon
      treatment with H2O2. Immunostaining and microtubule fractionation assay revealed
      that microtubules were depolymerized in the cells that had been treated with
      H2O2. To understand the effect of microtubules depolymerization on the
      mitochondrial mass, we treated the cells with several kinds of microtubule-active
      drugs, which arrest cultured cells at the G2/M phase. The results showed that
      mitochondrial mass and mtDNA copy number all were increased after such
      treatments. Taking these findings together, we suggest that oxidative stress
      induced microtubule derangement is one of the molecular events involved in the
      increase of mitochondrial mass upon treatment of human cells with H2O2.

PMID- 15965070
TI  - Blood lipid peroxides and muscle damage increased following intensive resistance
      training of female weightlifters.
AB  - The aim of this study was to examine changes in muscle cell injury and
      antioxidant capacity of weightlifters following a 1-week intensive resistance
      training regimen. Thirty-six female subjects participated in this study, and
      their ages ranged from 18 to 25 years. The sample group included 19 elite
      weightlifters with more than 3 years of weightlifting training experience, while
      the control group comprised 17 non-athletic individuals. Compared with non
      athletes, weightlifters had significantly lower glutathione peroxidase activity
      and plasma vitamin C concentrations. Weightlifters also had significantly higher
      malondialdehyde + 4-hydroxy 2-(E)-nonenal (MDA+4-HNE) and thiobarbituric acid
      reactive substance (TBARS) levels and creatine kinase (CK) activity. For
      weightlifters, the plasma vitamin E level and the activity of superoxide
      dismutase (SOD) decreased, and CK activity increased significantly (P < 0.05)
      after a 1-week intensive resistance-training regimen. Both the TBARS levels and
      CK activity returned to values of pre-intensive training after a 2-day rest. The
      MDA+4-HNE level strongly correlated with CK activity in weightlifters (P < 0.05).
      In conclusion, both long-term exercise training and 1 week of intensive
      resistance training resulted in increased oxidative stress and cell injury in
      female weightlifters. Furthermore, proper rest after intensive training was found
      to be important for recovery.

PMID- 15965072
TI  - Protective effect of alpha-keto-beta-methyl-n-valeric acid on BV-2 microglia
      under hypoxia or oxidative stress.
AB  - The alpha-ketoglutarate dehydrogenase complex (KGDHC) is a mitochondrial enzyme
      in the TCA cycle. Inhibition of KGDHC activity by alpha-keto-beta-methyl-n
      valeric acid (KMV) is associated with neuron death. However, the effect of KMV in
      microglia is unclear. Therefore, we investigated the effect of KMV on BV-2
      microglial cells exposed to hypoxia or oxidative stress. The results showed that
      KMV (1-20 mM) enhanced the cell viability under hypoxia. KMV dose-dependently
      reduced ROS and LDH releases from hypoxic BV-2 cells. KMV also reduced ROS
      production and enhanced the cell viability under H2O2 but failed to reduce the
      SIN-1 and sodium nitroprusside (SNP) toxicity. KMV also reduced caspase-3 and -9
      activation under stress. These results suggest that KMV protects BV-2 cells from
      stress and acts by reducing ROS production through inhibition of KDGHC.

PMID- 15965071
TI  - Anti-inflammatory and antioxidative effects of propofol on lipopolysaccharide
      activated macrophages.
AB  - Sepsis is a serious and life-threatening syndrome that often occurs in intensive
      care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide
      (NO) can be overproduced, causing tissue and cell injury. Propofol is an
      intravenous agent used for sedation of ICU patients. Our previous study showed
      that propofol has immunosuppressive effects on macrophage functions. This study
      was designed to evaluate the anti-inflammatory and antioxidative effects of
      propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha),
      interleukin 1beta (IL-1beta), IL-6, and NO in lipopolysaccharide (LPS)- activated
      macrophages. Exposure to a therapeutic concentration of propofol (50 microM), LPS
      (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not
      cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF
      alpha, IL-1beta, and IL-6 protein levels in a time-dependent manner, whereas
      propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1beta,
      and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1beta,
      and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO
      production and inducible nitric oxide synthase (iNOS) expression in macrophages.
      Exposure of macrophages to propofol significantly inhibited the LPS-induced NO
      biosynthesis. The present study shows that propofol, at a therapeutic
      concentration, has anti-inflammatory and antioxidative effects on the
      biosyntheses of TNF-alpha, IL-1beta, IL-6, and NO in LPS-activated macro-phages
      and that the suppressive effects are exerted at the pretranslational level.

PMID- 15965073
TI  - Oxidative toxicity in BV-2 microglia cells: sesamolin neuroprotection of H2O2
      injury involving activation of p38 mitogen-activated protein kinase.
AB  - Reactive oxygen species (ROS) has been proposed to play a pathogenic role in
      neuronal injury. Sesame antioxidants that inhibit lipid peroxidation and regulate
      cytokine production may suppress ROS generation. In this study, we focused on the
      effect of sesamolin on H2O2-induced neurotoxicity and ROS production in the
      murine microglial cell line BV-2. Results indicate that the H2O2 elicited BV-2
      cell death in a concentration- and time-dependent manner. ROS generation in BV-2
      cells was time-dependently increased by the H2O2 treatment. Sesamolin reduced ROS
      generation in BV-2 cells. p38 mitogen-activated protein kinase (MAPK) and caspase
      3 were also activated in BV-2 cells under H2O2 stress. Sesamolin was able to
      inhibit H2O2-induced p38 MAPK and caspase-3 activation and cell death. In
      addition, sesamolin preserved superoxide dismutase and catalase activities in BV
      2 cells under H2O2 stress. In conclusion, sesamolin protects microglia against
      H2O2-induced cell injury and this protective effect was accompanied by its
      inhibition of p38 MAPK and caspase-3 activation and ROS production.

PMID- 15965074
TI  - Angiotensin II stimulates hypoxia-inducible factor 1alpha accumulation in
      glomerular mesangial cells.
AB  - Hypoxia increases hypoxia-inducible factor 1alpha (HIF-1alpha) protein levels by
      inhibiting ubiquitination and degradation of HIF-1alpha, which regulates the
      transcription of many genes. Recent studies have revealed that many ligands can
      stimulate HIF-1alpha accumulation under nonhypoxic conditions. In this study, we
      show that angiotensin II (Ang II) increased HIF-1alpha protein levels in a time-
      and dose-dependent manner under normoxic conditions. Treatment of mesangial cells
      with Ang II (100 nM) increased production of reactive oxygen species (ROS). Ang
      II (100 nM) increased the phosphorylation of PDK-1 and Akt/PKB in glomerular
      mesangial cells. Ang II-stimulated HIF-1alpha accumulation was blocked by the
      phosphatidylinositol 3-kinase (PI-3K) inhibitors, Ly 294001, and wortmannin,
      suggesting that PI-3K was involved. Because increased ROS generation by Ang II
      may activate the PI-3K-PKB/Akt signaling pathway, these results suggest that Ang
      II may stimulate a ROS-dependent activation of the PI-3K-PKB/Akt pathway, which
      leads to HIF-1alpha accumulation.

PMID- 15965075
TI  - Effects of glucose and alpha-tocopherol on low-density lipoprotein oxidation and
      glycation.
AB  - Glycation of blood proteins is considered to be a major contributor to
      hyperglycemic complications in diabetes mellitus patients. In this study, we
      demonstrate the efficacy of alpha-tocopherol in reducing low-density lipoprotein
      (LDL) oxidation and glycation in vitro. Native LDL isolated from healthy subjects
      was exposed to various concentrations of glucose and malondialdehyde (MDA) with
      or without alpha-tocopherol enrichment for 7 days in sealed vacuum ampoules. The
      degree of glycation, copper-induced lag time, content of thiobarbituric acid
      reactive substances (TBARS), and alpha-tocopherol levels in LDL were then
      assessed. LDL lag time was significantly reduced with high levels of glucose and
      MDA. Alpha-tocopherol enrichment dramatically inhibited the oxidation of LDL in
      the lag-time assay. However, the length of incubation time was inversely related
      to the LDL lag time. Longer incubation time resulted in shorter LDL lag time,
      with or without alpha-tocopherol enrichment. The level of TBARS associated with
      LDL oxidation was highest in native, MDA-supplemented, and high-glucose samples.
      The alpha-tocopherol levels were inversely related to glucose levels and
      incubation times. In conclusion, high-glucose concentrations heightened the
      oxidative susceptibility of LDL. Alpha-tocopherol enrichment reduced this trend
      and prevented LDL from undergoing architectural modification.

PMID- 15965076
TI  - Identification of three mutations in the Cu,Zn-superoxide dismutase (Cu,Zn-SOD)
      gene with familial amyotrophic lateral sclerosis: transduction of human Cu,Zn-SOD
      into PC12 cells by HIV-1 TAT protein basic domain.
AB  - The most frequent genetic causes of amyotrophic lateral sclerosis (ALS)
      determined so far are mutations occurring in the gene coding for copper/zinc
      superoxide dismutase (Cu,Zn-SOD). The mechanism may involve the formation of
      hydroxyl radicals or malfunctioning of the SOD protein. Wild-type SOD1 was
      constructed into a transcription-translation expression vector to examine the
      SOD1 production in vitro. Wild-type SOD1 was highly expressed in Escherichia
      coli. Active SOD1 was expressed in a metal-dependent manner. To investigate the
      possible roles of genetic causes of ALS, a human Cu,Zn-SOD gene was fused with a
      gene fragment encoding the nine amino acid transactivator of transcription (Tat)
      protein transduction domain (RKKRRQRRR) of human immunodeficiency virus type 1 in
      a bacterial expression vector to produce a genetic in-frame Tat-SOD1 fusion
      protein. The expressed and purified Tat-SOD1 fusion proteins in E. coli can enter
      PC12 neural cells to observe the cellular consequences. Denatured Tat-SOD1 was
      successfully transduced into PC12 cells and retained its activity via protein
      refolding. Three point mutations, E21K, D90V, and D101G, were cloned by site
      directed mutagenesis and showed lower SOD1 activity. In undifferentiated PC12
      cells, wild-type Tat-SOD1 could prevent DNA fragmentation due to superoxide anion
      attacks generated by 35 mM paraquat, whereas mutant Tat-D101G enhanced cell
      death. Our results demonstrate that exogenous human Cu,Zn-SOD fused with Tat
      protein can be directly transduced into cells, and the delivered enzymatically
      active Tat-SOD exhibits a cellular protective function against oxidative stress.

PMID- 15965077
TI  - Kainic acid-induced oxidative injury is attenuated by hypoxic preconditioning.
AB  - Female Wistar rats were subjected to 380 mmHg in an altitude chamber for 15 h/day
      for 28 days. Hypoxic preconditioning attenuated kainic acid (KA)-induced
      oxidative injury, including KA-elevated lipid peroxidation and neuronal loss in
      rat hippocampus. Furthermore, KA-induced translocation of cytochrome c and
      apoptosis-inducing factor from mitochondria to cytosol was attenuated in the
      hypoxic rats. In addition, hypoxic preconditioning attenuated the KA-induced
      reduction in glutathione content and superoxide dismutase as well as KA-induced
      increase in glutathione peroxidase. Although local infusion of KA increased
      hippocampal NF-kappaB binding activity in the normoxic rat, hypoxia further
      enhanced KA-elevated NF-kappaB binding activity. Moreover, hypoxic
      preconditioning potentiated the KA-induced increase in Bcl-2 level in the
      lesioned hippocampus. Our data suggest that hypoxic preconditioning exerts its
      neuroprotection of KA-induced oxidative injury via enhancing NF-kappaB
      activation, upregulating the antioxidative defense system, and attenuating the
      apoptotic process.

PMID- 15965078
TI  - Antioxidant N-acetylcysteine blocks nerve growth factor-induced H2O2/ERK
      signaling in PC12 cells.
AB  - We investigated whether H2O2, superoxide, and ERK participate in nerve growth
      factor (NGF)-induced signaling cascades and whether antioxidant N-acetylcysteine
      (NAC) regulates these NGF-induced responses. PC12 cells were cultured in medium
      containing NGF or vehicle with or without NAC pretreatment, and the intracellular
      H2O2 and superoxide levels and the amount of phosphorylated ERK were evaluated by
      flow cytometry and Western blotting, respectively. We found that NGF increased
      intracellular H2O2 concentration and activated ERK but failed to affect
      intracellular superoxide level. Moreover, NAC counteracted these NGF-induced
      responses. These findings demonstrate that NAC blocks the NGF-induced H2O2/ERK
      signaling in PC12 cells.

PMID- 15965079
TI  - Effect of enhanced prostacyclin synthesis by adenovirus-mediated transfer on
      lipopolysaccharide stimulation in neuron-glia cultures.
AB  - Prostacyclin (PGI2) is known as a short-lived, potent vasodilator and platelet
      anti-aggregatory eicosanoid. This work attempts to selectively augment PGI2
      synthesis in neuron-glia cultures by adenoviral (Ad) gene transfer of PGI
      synthase (PGIS) or bicistronic cyclooxygenase 1 (COX-1)/PGIS and examines whether
      PGI2 confers protection against lipopolysaccharide (LPS) stimulation. Cultures
      released low levels of eicosanoids. Upon Ad-PGIS or Ad-COX-1/PGIS infection,
      cultures selectively increased prostacyclin release. Both PGIS- and COX-1/PGIS
      overexpressed cultures contained fewer microglial numbers. Further, they
      significantly attenuated LPS-induced iNOS expression and lactate, nitric oxide,
      and TNF-alpha production. Taken together, enhanced prostacyclin synthesis in
      neuron-glial cultures reduced microglia number and suppressed LPS stimulation.

PMID- 15965080
TI  - Potential mechanism of blood vessel protection by resveratrol, a component of red
      wine.
AB  - Resveratrol-mediated heme oxgenase-1 (HO-1) induction has been shown to occur in
      primary neuronal cultures and has been implicated as having potential
      neuroprotective action. Further, antioxidant properties of resveratrol have been
      reported to protect against coronary heart disease. We attempted to examine the
      HO-1 inducing potency of resveratrol and the regulatory mechanism of its
      induction in rat aortic smooth muscle cells (RASMC). We showed that resveratrol
      induced HO-1 expression was concentration- and time-dependent. The level of HO-1
      expression and its promoter activity mediated by resveratrol was attenuated by
      nuclear factor-kappa B (NF-kappaB) inhibitors, but not by mitogen-activated
      protein kinase (MAPK) inhibitors. Deletion of NF-kappaB binding sites in the
      promoter region strongly reduced luciferase activity. Collectively, we suggest
      that resveratrol-mediated HO-1 expression occurs, at least in part, through the
      NF-kappaB pathway.

PMID- 15965081
TI  - Pravastatin attenuates ceramide-induced cytotoxicity in mouse cerebral
      endothelial cells with HIF-1 activation and VEGF upregulation.
AB  - Ceramide is a pro-apoptotic lipid messenger that induces oxidative stress and may
      mediate apoptosis in cerebral endothelial cells (CECs) induced by TNF
      alpha/cycloheximide, lipopolysaccharide, oxidized LDL, IL-1, and amyloid peptide.
      Exposure of CECs to C2 ceramide for 12 h caused cell death in a concentration
      dependent manner, with a LC50 of 30 microM. Statins are inhibitors of 3-hydroxyl
      3-methyl coenzyme A reductase which is the rate-limiting enzyme for cholesterol
      biosynthesis. Pretreatment with pravastatin at 20 microM for 16 h substantially
      attenuated ceramide cytotoxicity in mouse CECs. Increases in vascular endothelial
      growth factor (VEGF) expression were detected within 1-3 h after pravastatin
      treatment. This pravastatin action was accompanied by the activation of hypoxia
      inducible factor-1 (HIF-1), a transcription factor known to activate VEGF
      expression. These results raise the possibility that pravastatin may protect CECs
      against ceramide-induced death via the HIF-VEGF cascade.

PMID- 15965082
TI  - Alleviation of oxidative damage in multiple tissues in rats with streptozotocin
      induced diabetes by rice bran oil supplementation.
AB  - The possibility of 8-hydroxy-2'-deoxyguanosine (8-OHdG) serving as a sensitive
      biomarker of oxidative DNA damage and oxidative stress was investigated. Reactive
      oxygen species (ROS) have been reported to be a cause of diabetes induced by
      chemicals such as streptozotocin (STZ) in experimental animals. In this study, we
      examined oxidative DNA damage in multiple tissues in rats with STZ-induced
      diabetes by measuring the levels of 8-OHdG in the liver, kidney, pancreas, brain,
      and heart. Levels of 8-OHdG in mitochondrial DNA (mtDNA) and nuclear DNA (nDNA)
      were also determined in multiple tissues of rats treated with rice bran oil.
      Levels were 0.19 +/- 0.07, 0.88 +/- 0.30, 1.97 +/- 0.05, and 9.79 +/- 3.09
      (1/10(5) dG) in the liver of nDNA of normal rats, nDNA of STZ-induced diabetic
      rats, mtDNA of normal rats, and mtDNA of STZ-induced diabetic rats, respectively.
      Levels of mtDNA of 8-OHdG were 10 times higher than those of nDNA in multiple
      tissues. Significant reductions in mtDNA 8-OHdG levels were seen in the liver,
      kidney, and pancreas of diabetic rats treated with rice bran oil compared with
      diabetic rats without intervention. Our study demonstrated that oxidative mtDNA
      damage may occur in multiple tissues of STZ-induced diabetics rats. Intervention
      with rice bran oil treatment may reverse the increase in the frequency of 8-OHdG.

PMID- 15965083
TI  - Curcumin inhibits ROS formation and apoptosis in methylglyoxal-treated human
      hepatoma G2 cells.
AB  - Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly
      from glycolytic intermediates. Elevated MG levels in diabetes patients are
      believed to contribute to diabetic complications. MG is cytotoxic through
      induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known
      to have antioxidant and anti-inflammatory properties. In the present study, we
      investigated the effect of curcumin on MG-induced apoptotic events in human
      hepatoma G2 cells. We report that curcumin prevented MG-induced cell death and
      apoptotic biochemical changes such as mitochondrial release of cytochrome c,
      caspase-3 activation, and cleavage of PARP (poly [ADP-ribose] polymerase). Using
      the cell permeable dye 2',7'-dichlorofluorescein diacetate (DCF-DA) as an
      indicator of reactive oxygen species (ROS) generation, we found that curcumin
      abolished MG-stimulated intracellular oxidative stress. The results demonstrate
      that curcumin significantly attenuates MG-induced ROS formation, and suggest that
      ROS triggers cytochrome c release, caspase activation, and subsequent apoptotic
      biochemical changes.

PMID- 15965084
TI  - Prevention of cellular oxidative damage by an aqueous extract of Anoectochilus
      formosanus.
AB  - Anoectochilus formosanus (AF) is a popular folk medicine in Taiwan whose
      pharmacological effects have been characterized. In this work we investigated the
      antioxidant properties of an aqueous extract prepared from AF. The AF extract was
      capable of scavenging H2O2 in a dose-dependent manner. We induced oxidative
      stress in HL-60 cells, either by the addition of hydrogen peroxide (H2O2) or by
      the xanthine/xanthine oxidase reaction. Apoptosis caused by oxidative damage was
      displayed by DNA fragmentation on gel electrophoresis, and the apoptotic fraction
      was quantified with flow cytometry. The cell damage induced by oxidative stress
      was prevented by the plant extract in a concentration-dependent manner.
      Furthermore, the proteolytic cleavage of poly(ADP-ribose) polymerase during the
      apoptotic process was also inhibited by AF extract. Our results provide the basis
      for determining an AF extract to be an antioxidant.

PMID- 15965085
TI  - Inhibitory effects of a rice hull constituent on tumor necrosis factor alpha,
      prostaglandin E2, and cyclooxygenase-2 production in lipopolysaccharide-activated
      mouse macrophages.
AB  - Isovitexin, isolated from rice hull of Oryza sativa, has been characterized as a
      potent antioxidant. Its antioxidant activity, determined on the basis of
      inhibition of lipid peroxidation by the Fenton reaction, was comparable with that
      of alpha-tocopherol, a well-established antioxidant. Isovitexin was able to
      reduce the amount of hydrogen peroxide production induced by lipopolysaccharide
      (LPS) in mouse macrophage RAW264.7 cells. In this study, we assessed its effects
      on the production of tumor necrosis factor alpha (TNF-alpha), prostaglandin E2
      (PGE2), and the expression of cyclooxygenase-2 (COX-2) in LPS-activated RAW 264.7
      macrophages. Isovitexin inhibited the release of TNF-alpha, a proinflammatory
      cytokine, upon LPS activation with a 50% inhibitory concentration (IC50) of 78.6
      microM. Isovitexin markedly reduced LPS-stimulated PGE2 production in a
      concentration-dependent manner, with an IC50 of 80.0 microM. The expression of
      COX-2 was also inhibited by isovitexin treatment. Our results suggest that
      suppression of ROS-mediated COX-2 expression by isovitexin is beneficial in
      reducing inflammation and carcinogenesis.

PMID- 15965086
TI  - Raffinee in the treatment of spinal cord injury: an open-labeled clinical trial.
AB  - The purpose of this preliminary clinical trial was to assess the safety and
      therapeutic trend of Raffinee, a mixture of free radical scavengers derived from
      natural products, on subacute spinal cord injury (SCI). SCI patients (three
      females and seven males) were enrolled from three medical centers in Taiwan.
      Their ages ranged from 18 to 76 years, with an average of 47.6 +/- 19.0 years.
      There were four incomplete and six complete cases in this study. Standard
      regimens for SCI at acute stage were given at each hospital. Approximately 7
      weeks (35.4 +/- 13.9 days) after SCI, 2 U of Raffinee was given orally before
      meals three times a day for 6 weeks. Patients received motor, sensory, and
      activities of daily living (ADL) assessments before and after the treatment with
      Raffinee every week for 6 weeks. The Wilcoxon signed-ranks test was used for
      statistical analysis. Significant motor and sensory recovery began in the second
      week of Raffinee treatment, and significant ADL recovery was also noted in the
      third week. Functional recovery was more prominent in incomplete cases. Raffinee
      appeared to be safe in the subacute stage of SCI and may be an effective adjuvant
      therapy for enhancing functional recovery. Further clinical studies including
      double-blinded randomized placebo-controlled trials with follow-up for more than
      1 year are necessary to validate the effectiveness of Raffinee in SCI.

PMID- 15965087
TI  - Induction of thioredoxin and mitochondrial survival proteins mediates
      preconditioning-induced cardioprotection and neuroprotection.
AB  - Delayed cardio- and neuroprotection are observed following a preconditioning
      procedure evoked by a brief and nontoxic oxidative stress due to deprivation of
      oxygen, glucose, serum, trophic factors, and/or antioxidative enzymes.
      Preconditioning protection can be observed in vivo and is under clinical trials
      for preservation of cell viability following organ transplants of liver. Previous
      studies indicated that ischemic preconditioning increases the expression of heat
      shock proteins (HSPs) and nitric oxide synthase (NOS). Our pilot studies indicate
      that the treatment of neuronal NOS inhibitor (7-nitroindazole) and 6Br-cGMP
      blocks and mimics, respectively, preconditioning protection in human
      neuroblastoma SH-SY5Y cells. This minireview focuses on nitric oxide-mediated
      cellular adaptation and the related cGMP/PKG signaling pathway in a compensatory
      mechanism underlying preconditioning-induced hormesis. Both preconditioning and
      6Br-cGMP increase the induction of human thioredoxin (Trx) mRNA and protein for
      cytoprotection, which is largely prevented by transfection of cells with Trx
      antisense but not sense oligonucleotides. Cytosolic Trx1 and mitochondrial Trx2
      suppress free radical formation, lipid peroxidation, oxidative stress, and
      mitochondria-dependent apoptosis; knock out/down of either Trx1 or Trx2 is
      detrimental to cell survival. Other recent findings indicate that a transgenic
      increase of Trx in mice increases tolerance against oxidative nigral injury
      caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Trx1 can be
      translocated into nucleus and phosphoactivated CREB for a delayed induction of
      mitochondrial anti-apoptotic Bcl-2 and antioxidative MnSOD that is known to
      increase vitality and survival of cells in the brain and the heart. In
      conclusion, preconditioning adaptation or a brief oxidative stress induces a
      delayed nitric oxide-mediated compensatory mechanism for cell survival and
      vitality in the central nervous system and the cardiovascular system.
      Preconditioning-induced adaptive tolerance may be signaling through a cGMP
      dependent induction of cytosolic redox protein Trx1 and subsequently
      mitochondrial proteins such as Bcl-2, MnSOD, and perhaps Trx2 or HSP70.

PMID- 15965088
TI  - Mitochondrion-targeted photosensitizer enhances the photodynamic effect-induced
      mitochondrial dysfunction and apoptosis.
AB  - Recently, the mitochondrion has been considered as a novel pharmacological target
      for anticancer therapy due to its crucial role involved in arbitrating cell
      apoptosis. We have previously demonstrated that 488-nm laser irradiation induced
      a specific mitochondrial reactive oxygen species (mROS) formation and apoptotic
      death. In this study, we used a second generation of photosensitizers, the
      benzoporphyrin-derivative monoacid ring A (BPD-MA). We investigated specifically
      mechanisms at the mitochondrial level for BPD-MA coupled with 690-nm laser
      irradiation, the photodynamic effect (PDE) of BPD-MA, using conventional and
      laser scanning imaging microscopy in intact C6 glioma cells. We demonstrated BPD
      MA localized mainly in the mitochondrial area. The phototoxicity induced by 1-10
      J 690-nm laser irradiation was minor as compared to that induced by 488-nm laser
      irradiation. Unlike other mitochondrion-targeted photosensitizers, the dark
      toxicity induced by BPD-MA (0.05-5 mg/mL, effective doses used for the PDE) was
      relatively low. Nevertheless, the PDE of BPD-MA using 0.5 mg/mL coupled with 5J
      690-nm irradiation induced profound and rapid (< 1 min) mitochondrial swelling,
      mROS formation, and severe plasma membrane blebbing as compared to that induced
      by 488-nm laser irradiation (< 10 min). Later, the PDE of BPD-MA resulted in
      positive propidium iodide cell-death stain and positive TUNEL apoptotic nuclear
      stain and DNA laddering. Finally, the PDT of BPD-MA also instantaneously promoted
      the mitochondrion to diminish its covalent binding with a mitochondrial marker,
      MitoTracker Green. We conclude that the PDT of BPD-MA targeted primarily and
      compellingly the mitochondrion to induce effective mitochondria-mediated
      apoptosis and thus may serve as a powerful photosensitizer for clinical cancer
      therapy.

PMID- 15965089
TI  - Attenuation of UV-induced apoptosis by coenzyme Q10 in human cells harboring
      large-scale deletion of mitochondrial DNA.
AB  - Chronic progressive external ophthalmoplegia (CPEO) syndrome is one of the
      mitochondrial diseases caused by large-scale deletions in mitochondrial DNA
      (mtDNA) that impair the respiratory function of mitochondria and result in
      decreased production of ATP in affected tissues. In order to investigate whether
      CPEO-associated mtDNA mutations (i.e., 4,366-bp and 4,977-bp large-scale
      deletions) render human cells more vulnerable to apoptosis, we constructed
      cybrids carrying the deleted mtDNA. Assays for cell viability, DNA fragmentation,
      cytochrome c release, and caspase 3 activation revealed that UV irradiation at 20
      J/m2 triggered apoptosis in all the cybrids. This treatment also produced
      elevated intracellular levels of reactive oxygen species (ROS). The rate of UV
      induced cell death was more pronounced in the cybrids harboring mtDNA deletions
      than in the control cybrid with wild-type mtDNA. Subsequently, we evaluated the
      effect of coenzyme Q10 on the UV-triggered apoptosis. The results showed that
      after pretreatment of the cybrids with 100 microM coenzyme Q10 the UV-induced
      cell damage (i.e., ROS production and activation of caspase 3) was significantly
      reduced. Taken together, these findings suggest that large-scale deletions of
      mtDNA increased the susceptibility of human cells to the UV-triggered apoptosis
      and that coenzyme Q10 mitigated the damage; hence, it might potentially serve as
      a therapeutic agent to treat mitochondrial diseases resulting from mtDNA
      deletions.

PMID- 15965090
TI  - Antisense RNA to inducible nitric oxide synthase reduces cytokine-mediated brain
      endothelial cell death.
AB  - We test whether inhibition of inducible nitric oxide synthase (iNOS) can exert a
      cytoprotective effect on cerebral endothelial cells upon stimulation by pro
      inflammatory cytokines. Mouse brain endothelial cells were stably transfected to
      express an antisense RNA against iNOS driven by an endothelium-specific von
      Willebrand factor (vWF) promoter. Upon stimulation with tumor necrosis factor
      alpha (TNF-alpha) plus interferon-gamma (IFN-gamma), antisense transfectants
      showed less iNOS enzymatic activity with less nitric oxide (NO) when compared to
      the sense control cells. Correspondingly, the antisense cells showed a reduced
      LDH release and less cytosolic content of oligonucleosomes. These findings
      establish a cell-specific antisense strategy and confirm the cytotoxic role of
      iNOS expression in cultured cerebral endothelial cells.

PMID- 15965091
TI  - 2,6-Diisopropylphenol protects osteoblasts from oxidative stress-induced
      apoptosis through suppression of caspase-3 activation.
AB  - 2,6-Diisopropylphenol is an intravenous anesthetic agent used for induction and
      maintenance of anesthesia. Since it is similar to alpha-tocopherol, 2,6
      diisopropylphenol may have antioxidant effects. Osteoblasts play important roles
      in bone remodeling. In this study, we attempted to evaluate the protective
      effects of 2,6-diisopropylphenol on oxidative stress-induced osteoblast insults
      and their possible mechanisms, using neonatal rat calvarial osteoblasts as the
      experimental model. Clinically relevant concentrations of 2,6-diisopropylphenol
      (3 and 30 microM) had no effect on osteoblast viability. However, 2,6
      diisopropylphenol at 300 microM time-dependently caused osteoblast death.
      Exposure to sodium nitroprusside (SNP), a nitric oxide donor, increased amounts
      of nitrite in osteoblasts. 2,6-Diisopropylphenol did not scavenge basal or SNP
      releasing nitric oxide. Hydrogen peroxide (HP) enhanced levels of intracellular
      reactive oxygen species in osteoblasts. 2,6-Diisopropylphenol significantly
      reduced HP-induced oxidative stress. Exposure of osteoblasts to SNP and HP
      decreased cell viability time-dependently. 2,6-Diisopropylphenol protected
      osteoblasts from SNP- and HP-induced cell damage. Analysis by a flow cytometric
      method revealed that SNP and HP induced osteoblast apoptosis. 2,6
      Diisopropylphenol significantly blocked SNP- and HP-induced osteoblast apoptosis.
      Administration of SNP and HP increased caspase-3 activities. However, 2,6
      diisopropylphenol significantly decreased SNP- and HP-enhanced caspase-3
      activities. This study shows that a therapeutic concentration of 2,6
      diisopropylphenol can protect osteoblasts from SNP- and HP-induced cell insults,
      possibly via suppression of caspase-3 activities.

PMID- 15965092
TI  - Nitric oxide induces osteoblast apoptosis through a mitochondria-dependent
      pathway.
AB  - Osteoblasts contribute to bone remodeling. Nitric oxide can regulate osteoblast
      activities. In this study, we attempted to evaluate the pathophysiological
      effects of nitric oxide on osteoblasts and its possible mechanism using neonatal
      rat calvarial osteoblasts as the experimental model. Exposure of osteoblasts to
      sodium nitroprusside, a nitric oxide donor, decreased alkaline phosphatase
      activities and cell viability in a concentration- and time-dependent manner.
      Apoptotic analysis revealed that sodium nitroprusside time-dependently increased
      the percentages of osteoblasts undergoing apoptosis. Administration of sodium
      nitroprusside reduced the mitochondrial membrane potential of osteoblasts. In
      parallel with the mitochondrial dysfunction, levels of intracellular reactive
      oxygen species and cytochrome c were significantly elevated following sodium
      nitroprusside administration. Exposure of osteoblasts to sodium nitroprusside
      significantly increased caspase-3 activity. Results of this study show that
      nitric oxide, decomposed from sodium nitroprusside, can induce osteoblast
      apoptosis through a mitochondrion-dependent cascade that causes mitochondrial
      dysfunction, release of intracellular reactive oxygen species and cytochrome c
      from mitochondria to cytoplasm, and activation of caspase-3.

PMID- 15965093
TI  - Bcl-2 gene family expression in the brain of rat offspring after gestational and
      lactational dioxin exposure.
AB  - Recent epidemiological studies have shown that dioxin, a persistent organic
      pollutant, is related to cognitive and behavioral abnormalities in the offspring
      of exposed cohort. In order to investigate the possible impact of dioxin in
      survival gene expression during brain development, we established an animal model
      of gestational and lactational dioxin-exposed rat offspring. The expressions of
      dioxin-responsive gene cytochrome P450 1A1 (CYP1A1), apoptotic gene Bax, and anti
      apoptotic genes Bcl-2 and Bcl-xL were examined in rat liver and brains using
      Western blot analysis and RT-PCR. The results showed that treatment of pregnant
      rats with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (2 microg/kg body weight
      through oral delivery) at gestation day 15 resulted in an increase of Bcl-xL in
      offspring male liver and cerebral cortex, but a decrease in female offspring. In
      contrast, the expression of Bcl-xL in the cerebellum was decreased in male, but
      increased in female. Bcl-2, another anti-apoptotic gene, was also downregulated
      in P0 female liver, cerebral cortex, but was not observed in male. In the 4-month
      old offspring, however, the Bcl-2 protein levels in the liver and cerebellum of
      both male and female pups were higher in the TCDD group as compared with the
      control group. However, the Bcl-2 level in the cerebral cortex of TCDD-treated
      groups was higher than the control group only in female but not male offspring at
      4 months old. The expression of Bax showed no significant changes upon TCDD
      exposure at P0 stage, but was significantly reduced in the 4-month-old male
      cortex. These results indicate that early exposure of dioxin could affect the
      development of certain brain regions with gender difference, in terms of its
      differential effect on expressions of Bcl-xL, Bcl-2, and Bax.

PMID- 15965094
TI  - IL-5 inhibits apoptosis by upregulation of c-myc expression in human
      hematopoietic cells.
AB  - Interleukin 5 (IL-5) inhibition of apoptosis is required throughout many
      hematopoietic lineages to regulate proliferation and differentiation. It is not
      clear how IL-5 mediates the intracellular molecular events regulating the anti
      apoptotic effect. The cell lines TF-1 and JYTF-1 expressed different amounts of
      the IL-5 receptor alpha (IL-5R alpha) subunit, which caused contrasting effects
      in response to IL-5. IL-5 supported the survival but not the anti-apoptotic
      activities of TF-1 cells, which have a low expression of IL-5R alpha. In
      contrast, IL-5 supported both the survival and the anti-apoptotic activities of
      JYTF-1 cells, which overexpressed IL-5R alpha compared to TF-1 cells. In this
      study, IL-5 stimulation increased Annexin V binding (indicative of apoptosis) in
      TF-1 cells and decreased apoptosis in JYTF-1 cells. The proto-oncogenes c-fos,
      fosB, and c-jun were not detected, whereas junB was induced by IL-5 stimulation
      in both types of cells. Most importantly, IL-5 significantly induced c-myc
      expression in JYTF-1 cells, but did not in TF-1 cells. These results are
      consistent with the possibility that IL-5 inhibits apoptosis in JYTF-1 cells via
      the upregulation of c-myc expression.

PMID- 15965095
TI  - Detection of apoptosis and necrosis in normal human lung cells using 1H NMR
      spectroscopy.
AB  - This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung
      cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live
      MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their
      types and the percentage of cell death were assessed on a flow cytometer. Cadmium
      (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells,
      respectively, as revealed by phosphatidylserine externalization on a flow
      cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm)
      to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the
      percentage of apoptosis and strongly and positively correlated with PI staining
      after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only
      increased slightly within 2-h Hg treatment, and longer Hg exposure failed to
      produce further increase. Following 2-h Hg exposure, the spectral intensity of
      choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in
      Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel
      tool with a quantitative potential to distinguish apoptosis from necrosis as
      early as the onset of cell death in normal human lung cells.

PMID- 15965096
TI  - Cadmium toxicity toward caspase-independent apoptosis through the mitochondria
      calcium pathway in mtDNA-depleted cells.
AB  - Mitochondria are believed to be integrators and coordinators of programmed cell
      death in addition to their respiratory function. Using mitochondrial DNA (mtDNA)
      depleted osteosarcoma cells (rho0 cells) as a cell model, we investigated the
      apoptogenic signaling pathway of cadmium (Cd) under a condition of mitochondrial
      dysfunction. The apoptotic percentage was determined to be around 58.0% after a
      24-h exposure to 25 microM Cd using flow cytometry staining with propidium iodine
      (PI). Pretreatment with Z-VAD-fmk, a broad-spectrum caspase inhibitor, failed to
      prevent apoptosis following Cd exposure. Moreover, Cd was unable to activate
      caspase 3 using DEVD-AFC as a substrate, indicating that Cd induced a caspase
      independent apoptotic pathway in rho0 cells. JC-1 staining demonstrated that
      mitochondrial membrane depolarization was a prelude to apoptosis. On the other
      hand, the intracellular calcium concentration increased 12.5-fold after a 2-h
      exposure to Cd. More importantly, the apoptogenic activity of Cd was almost
      abolished by ruthenium red, a mitochondrial calcium uniporter blocker. This led
      us to conclude that mtDNA-depleted cells provide an alternative pathway for Cd to
      conduct caspase-independent apoptosis through a mitochondria-calcium mechanism.

PMID- 15965097
TI  - Pectinesterase inhibitor from jelly fig (Ficus awkeotsang Makino) achene induces
      apoptosis of human leukemic U937 cells.
AB  - The antitumor activity of pectinesterase inhibitor (PEI), a group of cationic
      polypeptides, from jelly fig (Ficus awkeotsang Makino) achene was first examined
      as a treatment for leukemia in this study. PEI displayed strong growth inhibition
      against human leukemic U937 cells via induction of apoptosis in a dose- and time
      dependent manner. At a level of 50 microg/mL, PEI inhibited 90% of cell growth,
      and the concentration of PEI required to induce 50% of cell viability (LC50) was
      about 180 microg/mL. Meanwhile, cell cycle arrest at G2/M phase was observed when
      cells were incubated with 100 microg PEI/mL for 24 h. PEI displayed a dose
      dependent influence on mitochondria transmembrane potential (MTP, delta psi m) of
      cells when detected by a flow cytometry. MTP of more than 50% cells was reduced
      when cells were incubated with PEI at levels higher than 50 microg PEI/mL for 24
      h. In addition, PEI upregulated caspase-3 activity. Taken together, PEI potently
      inhibited the proliferation of human leukemic U937 cells via cell cycle arrest
      and apoptosis in association with MTP reduction and caspase-3 activation,
      respectively, and showed therapy potential for U937 cells.

PMID- 15965098
TI  - Enhancement of cisplatin-induced apoptosis and caspase 3 activation by depletion
      of mitochondrial DNA in a human osteosarcoma cell line.
AB  - Cisplatin is an anticancer drug that can induce apoptosis. In this study, we
      investigated the effect of mitochondrial DNA (mtDNA) depletion on cisplatin
      induced cell death using a human osteosarcoma cell line (143B) and mtDNA-depleted
      143B cells (143B-rho0). Results showed that cisplatin decreased cell survival in
      143B-rho0 cells. Moreover, cisplatin induced a greater extent of apoptosis
      associated DNA fragmentation and caspase 3 activation in 143B-rho0 cells. The
      release of mitochondrial cytochrome c into cytosol by cisplatin was enhanced more
      obviously in 143B cells than in 143B-rho0 cells; however, in the control group of
      143B-rho0 cells, it was already dramatically greater. Depletion of mtDNA may
      increase sensitivity of cells to cisplatin-induced apoptosis by enhancing caspase
      3 activation via both cytochrome c-dependent and -independent pathways.

PMID- 15965099
TI  - Thallium acetate induces C6 glioma cell apoptosis.
AB  - Thallium acetate is a known neurotoxic agent. In this study, we investigated the
      mechanisms by which thallium acetate induces cell cycle arrest and cell apoptosis
      in cultured LC6 glioma cells. Exposure of C6 glioma cells to thallium acetate
      decreased cell viability as demonstrated by the MTT assay. Incubation of thallium
      acetate arrested cell cycle progression at the G2/M phase and caused cellular
      apoptosis at 300 microM as determined by trypan blue exclusion and flow
      cytometric analysis. The G2/M arrest was associated with a decrease in expression
      of CDK2 protein and an upregulation of p53 and the CDK inhibitor p21(Cip1), but
      not p27(Kip1). Thallium acetate did not alter the protein levels of cyclin A and
      B; cyclin D1, D2, and D3; and CDK4 expression in C6 glioma cells. Incubation of
      C6 glioma cells with thallium acetate upregulated the expression of proapoptotic
      proteins Bad and Apaf and downregulated the expression of anti-apoptotic proteins
      Bcl-xL and Bcl-2. In conclusion, these data suggest that thallium acetate
      inhibits cell cycle progression at G2/M phase by suppressing CDK activity through
      the p53-mediated induction of the CDK inhibitor p21(Cip1). Impairment of cell
      cycle progression may trigger the activation of a mitochondrial pathway and
      shifts the balance in the Bcl-2 family toward the proapoptotic members, promoting
      the formation of the apoptosome and, consequently, apoptosis.

PMID- 15965101
TI  - Oxygen in the cultivation of stem cells.
AB  - Cultivation of stem cells, like all cells in culture, is performed under
      conditions that cannot and do not replicate normal physiologic conditions. For
      example, direct exposure of cultured monolayer cells to serum contents is
      normally prevented in vivo by the vasculature. The heterogeneity of cells and
      signals between different cell types in an organ is certainly not captured when a
      single cell type is grown and studied in vitro. Gases, in particular, are not
      accounted for in routine tissue culture. Oxygen is fundamental for life and its
      concentration is an important signal for virtually all cellular processes.
      Nonetheless, oxygen is rarely taken into account in culturing stem and other
      cells. This review will summarize work that highlights the importance of
      considering oxygen conditions for culturing and manipulating stem cells. Emphasis
      is placed on major phenotypic changes in response to oxygen, recognizing that
      oxygen-mediated transcriptional and post-translational effects are enormously
      complex, and beyond the scope of this review. The review emphasizes that oxygen
      is an important signal in all major aspects of stem cell biology including
      proliferation and tumorigenesis, cell death and differentiation, self-renewal,
      and migration.

PMID- 15965100
TI  - Effects of gonadotrophin-releasing hormone agonists on apoptosis of granulosa
      cells.
AB  - Granulosa cells are known to contribute to maturation of oocytes, and most of the
      growth factors exert their action via granulosa cells. It has been established
      that granulosa cell death during follicular atresia and luteolysis results from
      apoptosis. However, the precise mechanistic pathways of granulosa cell apoptosis
      have not yet been defined. In this study, we determined the proportions of
      apoptosis in granulosa cells treated with two kinds of gonadotrophin-releasing
      hormone agonists (GnRHa): buserelin and leuprorelin depot. The incidences of DNA
      fragmentation of human granulosa cells treated with buserelin and leuprorelin
      were 54.33% and 39.02%, respectively. The proportions of apoptotic bodies were
      6.04% and 4.29%, respectively. There was a significant difference in the
      proportions of DNA fragmentation between the two kinds of GnRHa-treated granulosa
      cells. The apoptosis pathway and associated protein expression in granulosa cells
      treated with GnRHa were also determined. The Bax molecule, a pro-apoptosis
      protein, was expressed in granulosa cells undergoing apoptosis. In contrast, Bcl
      2, an anti-apoptosis protein, could not be detected in the same group of
      granulosa cells. The distribution of cytochrome c determined via immunostaining
      showed a diffuse pattern, which most likely indicated that cytochrome c was
      translocated from mitochondria into the cytoplasm. Western blotting showed the
      expressions of caspase-9 and caspase-3 in patients' granulosa cells. The GnRHa
      effects on granulosa cells indicated a higher incidence of DNA fragmentation and
      apoptotic bodies in the buserelin-treated than in the leuprorelin depot-treated
      group. The granulosa cells go through the mitochondria-dependent apoptosis
      pathway; the indicated pro-apoptosis protein Bax was expressed and induced
      cytochrome c release from mitochondria, which then activated caspase-9 and
      caspase-3 until cell death occurred.

PMID- 15965102
TI  - DNA damage-induced programmed cell death: potential roles in germ cell
      development.
AB  - The detection of DNA damage is necessary to protect against proliferation of
      potentially harmful cells and often results in cell cycle arrest and programmed
      cell death. Key components of DNA damage signaling networks include ATM, CHK2,
      p53, and Bax. Mutations in these damage signaling systems are linked to
      tumorigenesis and developmental abnormalities. Expression of some of these genes
      in primordial germ cells (PGCs) argues that PGCs may utilize DNA damage-induced
      signaling mechanisms to select against germ cells that are genetically defective,
      thus maintaining the integrity of the germline. This paper summarizes the roles
      of these DNA damage signaling molecules and addresses their potential involvement
      in germ cell development.

PMID- 15965103
TI  - G protein-coupled receptor roles in cell migration and cell death decisions.
AB  - Recognition of external conditions and the elicitation of appropriate responses
      are critical to a cell's ability to adjust to various developmental and
      environmental cues. G protein-coupled receptors (GPCRs) are a large class of
      receptors that act to relay external information into the cell by initiating
      signaling pathways that allow the cell to adapt to its present conditions. There
      are numerous ligands that activate GPCRs to initiate a multitude of intracellular
      signaling cascades involved in critical decisions including cell growth,
      differentiation, proliferation, migration, survival, and death. This article
      focuses on the signaling pathways involved in cell migration, survival, and death
      decisions with an emphasis on germ cells from various organisms.

PMID- 15965104
TI  - Growth and differentiation of astrocytes and neural progenitor cells on
      micropatterned polymer films.
AB  - This paper investigates the influence of micropatterned polymers and chemical
      modification on neural progenitor cell growth and differentiation in co-culture
      systems with astrocytes. We sought to develop strategies to facilitate nerve
      regeneration using a synergistic combination of guidance cues, investigating the
      cellular mechanisms of nerve repair using adult rat hippocampal progenitor cells
      (AHPCs). Our studies have shown that this synergistic combination of physical,
      chemical, and biological cues can lead to oriented growth of astrocytes and
      progenitor cells, can control and accelerate neurite outgrowth and alignment in
      vitro, and may influence differentiation of progenitor cells.

PMID- 15965105
TI  - Cellular and molecular regulation of hematopoietic and intestinal stem cell
      behavior.
AB  - Two fundamental questions in stem cell research are what controls stem cell
      number in vivo and which signal pathways regulate self-renewal. Here we summarize
      our recent studies regarding the role of BMP signaling in regulation of stem cell
      behavior in both the hematopoietic and intestinal systems. These studies provide
      evidence to show that BMP signaling plays an important role in controlling stem
      cell number, at least in these two stem cell compartments. However, the BMP
      signal utilizes different mechanisms to fulfill this purpose: in the
      hematopoietic stem cell compartment it controls stem cell number through
      regulation of the niche size; in the intestinal stem cell compartment it directly
      controls self-renewal of stem cells through restriction of Wnt/beta-catenin
      activity. The Bmpr1a mutant mouse provided an elegant model which allowed us to
      identify the HSC niche, an enigma for more than 25 years. Our work provided more
      evidence to demonstrate the essential function of the niche in maintenance of
      stem cells and showed that multiple signals are required to maintain a balanced
      control of stem cell self-renewal.

PMID- 15965106
TI  - The function of the neuronal proteins Shc and huntingtin in stem cells and
      neurons: pharmacologic exploitation for human brain diseases.
AB  - The identification of intracellular molecules and soluble factors that are
      important for neuronal differentiation and survival are of critical importance
      for development of therapeutic strategies for brain diseases. First, the activity
      of these factors/molecules may be enhanced in vivo in the attempt to induce
      proper neuronal differentiation and integration of the resident stem cells.
      Second, these factors may be applied ex vivo to increase the recovery of neurons
      from stem cells. Third, for those intracellular molecules that play crucial roles
      in neuronal survival, identification of their downstream targets may give us the
      chance to develop drug screening assays that use these targets for therapeutic
      purposes. In recent years, it has become evident that intracellular signaling
      processes are critical mediators of the responses of neural stem cells and
      neurons to growth factors. Analysis of the mechanisms of signal transduction has
      led to the striking finding that a handful of conserved signaling pathways appear
      to be used in different combinations to specify a wide variety of tissues or
      cells. This review will focus on the mechanisms by which specific molecules
      control the transition from proliferation to differentiation of neural progenitor
      cells and the subsequent survival of postmitotic neurons; it also discusses how
      this knowledge may be exploited to increase the potential efficacy of stem cell
      replacement in the damaged brain.

PMID- 15965107
TI  - Engineering a dopaminergic phenotype in stem/precursor cells: role of Nurr1, glia
      derived signals, and Wnts.
AB  - Recent results from clinical trials using fetal tissue grafts in patients with
      Parkinson's disease (PD) have indicated that current surgical strategies for
      dopamine cell replacement therapy need to be improved in order to achieve better
      functional integration of the grafts and to avoid dyskinesias. Previous studies
      using rich dopaminergic (DA) cell suspensions have provided proof-of-concept that
      PD patients can benefit from cell replacement therapy. Stem cells have been
      proposed as better candidates for cell replacement therapy in PD since they can
      be standardized, expanded, and engineered in vitro. Recent developments indicate
      that cell preparations enriched in DA neurons can be generated in vitro, but
      their functional integration in animal models of disease is still far from
      optimal. This is not entirely surprising considering our limited knowledge of the
      development of DA neurons and the reduced number of factors that have been
      implemented in stem cell differentiation protocols. This review will focus on
      three aspects of DA neuron development: (1) the function of Nurr1 and retinoid X
      receptors (RXR) in the differentiation of DA precursors and in the survival of DA
      neurons; (2) the role of glia in DA neurogenesis and the differentiation of DA
      precursors; and (3) the function of the Wnt family of lipoproteins in the
      proliferation and differentiation of DA precursors. A greater understanding of
      the cellular and molecular mechanisms that control DA neuron development, as well
      as their functional integration in vivo, are likely to ultimately contribute to
      the development of novel stem cell replacement therapies for PD.

PMID- 15965108
TI  - Umbilical cord blood-derived stem cells and brain repair.
AB  - Human umbilical cord blood (HUCB) is now considered a valuable source for stem
      cell-based therapies. HUCB cells are enriched for stem cells that have the
      potential to initiate and maintain tissue repair. This potential is especially
      attractive in neural diseases for which no current cure is available.
      Furthermore, HUCB cells are easily available and less immunogenic compared to
      other sources for stem cell therapy such as bone marrow. Accordingly, the number
      of cord blood transplants has doubled in the last year alone, especially in the
      pediatric population. The therapeutic potential of HUCB cells may be attributed
      to inherent ability of stem cell populations to replace damaged tissues.
      Alternatively, various cell types within the graft may promote neural repair by
      delivering neural protection and secretion of neurotrophic factors. In this
      review, we evaluate the preclinical studies in which HUCB was applied for
      treatment of neurodegenerative diseases and for traumatic and ischemic brain
      damage. We discuss how transplantation of HUCB cells affects these disorders and
      we present recent clinical studies with promising outcome.

PMID- 15965109
TI  - Infusion of human umbilical cord blood ameliorates neurologic deficits in rats
      with hemorrhagic brain injury.
AB  - Umbilical cord blood is a rich source of hematopoietic stem cells. It is
      routinely used for transplantation to repopulate cells of the immune system.
      Recent studies, however, have demonstrated that intravenous infusions of
      umbilical cord blood can ameliorate neurologic deficits associated with ischemic
      brain injury in rodents. Moreover, the infused cells penetrate into the
      parenchyma of the brain and adopt phenotypic characteristics typical of neural
      cells. In the present study we tested the hypothesis that the administration of
      umbilical cord blood can also diminish neurologic deficits caused by
      intracerebral hemorrhage (ICH). Intracerebral hemorrhage is a major cause of
      morbidity and mortality, and at the present time there are no adequate therapies
      that can minimize the consequences of this cerebrovascular event. ICH was induced
      in rats by intrastriatal injections of collagenase to cause bleeding in the
      striatum. Twenty-four hours after the induction of ICH rats received intravenous
      saphenous vein infusions of human umbilical cord blood (2.4 x 10(6) to 3.2 to
      10(6) cells). Animals were evaluated using a battery of tests at day 1 after ICH,
      but before the administration of umbilical cord blood, and at days 7, and 14
      after ICH (days 6 and 13, respectively, after cord blood administration). These
      tests included a neurological severity test, a stepping test, and an elevated
      body-swing test. Animals with umbilical cord blood infusions exhibited
      significant improvements in (1) the neurologic severity test at 6 and 13 days
      after cord blood infusion in comparison to saline-treated animals (P < 0.05); (2)
      the stepping test at day 6 (P < 0.05); and (3) the elevated body-swing test at
      day 13 (P< 0.05). These results demonstrate that the administration of human
      umbilical cord blood cells can ameliorate neurologic deficits associated with
      intracerebral hemorrhage.

PMID- 15965110
TI  - How Wnt signaling affects bone repair by mesenchymal stem cells from the bone
      marrow.
AB  - Human mesenchymal stem cells (hMSCs) from bone marrow are a source of osteoblast
      progenitors in vivo, and under appropriate conditions they differentiate into
      osteoblasts ex vivo. The cells provide a convenient cell culture model for the
      study of osteogenic tissue repair in an experimentally accessible system. Recent
      advances in the field of skeletal development and osteogenesis have demonstrated
      that signaling through the canonical wingless (Wnt) pathway is critical for the
      differentiation of progenitor cell lines into osteoblasts. Inhibition of such
      signals can predispose hMSCs to cell cycle entry and prevent osteogenesis. Our
      investigation of the role of Wnt signaling in osteogenesis by hMSCs ex vivo has
      demonstrated that osteogenesis proceeds in response to bone morphogenic protein 2
      stimulation and is sustained by Wnt signaling. In the presence of Dkk-1, an
      inhibitor of Wnt signaling, the cascade is disrupted, resulting in inhibition of
      osteogenesis. Peptide mapping studies have provided peptide Dkk-1 agonists and
      the opportunity for the production of blocking antibodies. Anti-Dkk-1 strategies
      are clinically relevant since high serum levels of Dkk-1 are thought to
      contribute to osteolytic lesion formation in multiple myeloma and possibly some
      forms of osteosarcoma. Specific inhibitors of glycogen synthetase kinase 3beta
      (GSK3beta), which mimic Wnt signaling, may also have a therapeutic benefit by
      enhancing in vitro osteogenesis despite the presence of Dkk-1. Antibodies that
      block Dkk-1 and GSK3beta inhibitors may provide novel opportunities for the
      enhancement of bone repair in a variety of human diseases such as multiple
      myeloma and osteosarcoma.

PMID- 15965111
TI  - Human retinal progenitor cells grown as neurospheres demonstrate time-dependent
      changes in neuronal and glial cell fate potential.
AB  - The spatiotemporal birth order of the seven major classes of retinal cells is
      highly conserved among vertebrates. During retinal development, long projection
      neurons (ganglion cells) are produced first from resident progenitors, followed
      by the appearance of retinal interneurons, photoreceptors, and Muller glia. This
      sequence is maintained through the complex orchestration of cell-intrinsic and
      cell-extrinsic events and factors, including local influences between neighboring
      cells. Here we asked whether cultures of human prenatal retinal cells might also
      yield different ratios of cell types based on gestational age and time spent in
      vitro, thus recapitulating in vivo development. An established chopping technique
      was used to passage human prenatal retinal cells as neurospheres, avoiding the
      use of proteases and preserving cell-cell contacts and native microenvironments
      present in vivo. Retinal neurospheres cultured in this manner demonstrated
      specific patterns of growth over a limited time period, possibly reflecting
      trends in normal retinal development. Upon differentiation, immunocytochemical
      analysis revealed that retinal neurospheres produce predominantly glial cells
      with increasing gestational age and time in culture. Conversely, the percentage
      of betaIII tubulin-positive neurons declined over time. This provides information
      for optimizing culture systems aimed at the study of human retinal development
      and the generation of specific retinal cell types for therapeutic use or drug
      testing.

PMID- 15965112
TI  - Neural progenitor cell transplants into the developing and mature central nervous
      system.
AB  - When developing cell transplant strategies to repair the diseased or injured
      central nervous system (CNS), it is essential to consider host-graft interactions
      and how they may influence the outcome of the transplants. Recent studies have
      demonstrated that transplanted neural progenitor cells (NPCs) can differentiate
      and integrate morphologically into developing mammalian retinas. Is the ability
      to differentiate and to undergo structural integration into the CNS unique to
      specific progenitor cells, or is this plasticity a function of host environment,
      or both? To address these issues we have used the developing retina of the
      Brazilian opossum and have compared the structural integration of brain and
      retinal progenitor cells transplanted into the eyes at different developmental
      stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless
      marsupial native to South America. This animal's lack of a pouch and fetal-like
      nature at birth circumvents the need for in utero surgical procedures, and thus
      provides an ideal environment in which to study the interactions between
      developing host tissues and transplanted NPCs. To test whether NPCs affect visual
      function we transplanted adult hippocampal progenitor cells (AHPCs) into normal,
      healthy adult rat eyes and performed noninvasive functional recordings.
      Monitoring of the retina and optic nerve over time by electroretinography and
      pupillometry revealed no severe perturbation in visual function in the transplant
      recipient eyes. Taken together, our findings suggest that the age of the host
      environment can strongly influence NPC differentiation and that transplantation
      of neural progenitor cells may be a useful strategy aimed at treating
      neurodegeneration and pathology of the CNS.

PMID- 15965113
TI  - Stem cells for retinal degenerative disorders.
AB  - Many systemic and eye-specific genetic disorders are accompanied by retinal
      degenerations that lead to blindness. In some of these diseases retinal
      degeneration occurs early in life and is quite rapid, whereas in other disorders,
      retinal degeneration starts later and progresses very slowly. At present, no
      therapies are available to patients for preventing or reversing the retinal
      degeneration that occurs in these diseases. Implantation of neural progenitor
      cells into the eye may be a means by which to retard or even reverse degeneration
      of the retina. To evaluate the potential of neural precursor cell implantation
      for treating retinal degenerative disorders, neuralized mouse embryonic stem
      cells from green fluorescent protein (GFP) transgenic mice were administered
      intravitreally to normal mice, mice with early retinal degeneration, and mice
      with slowly progressing retinal degeneration. In normal mice, the donor cells
      remained in the vitreous cavity and did not associate with the host retina. In
      mice with early retinal degeneration, implantation of the neural precursors was
      performed after the degeneration was almost complete. In these animals, the donor
      cells primarily associated closely with the inner surface of the retina, although
      a small fraction of donor cells did integrate into the host retina. Donor cells
      implanted in mice with slowly progressing retinal degeneration also associated
      with the inner retinal surface, but many more of the cells integrated into the
      retina. These findings indicate the importance of host tissue-donor cell
      interactions in determining the fate of implanted neural precursor cells. These
      interactions will be a major consideration when devising strategies for using
      cell implantation therapies for neurodegenerative disorders.

PMID- 15965114
TI  - Magnetic resonance tracking of implanted adult and embryonic stem cells in
      injured brain and spinal cord.
AB  - Stem cells are a promising tool for treating brain and spinal cord injury.
      Magnetic resonance imaging (MRI) provides a noninvasive method to study the fate
      of transplanted cells in vivo. We studied implanted rat bone marrow stromal cells
      (MSCs) and mouse embryonic stem cells (ESCs) labeled with iron-oxide
      nanoparticles (Endorem) and human CD34+ cells labeled with magnetic MicroBeads
      (Miltenyi) in rats with a cortical or spinal cord lesion. Cells were grafted
      intracerebrally, contralaterally to a cortical photochemical lesion, or injected
      intravenously. During the first week post transplantation, transplanted cells
      migrated to the lesion. About 3% of MSCs and ESCs differentiated into neurons,
      while no MSCs, but 75% of ESCs differentiated into astrocytes. Labeled MSCs,
      ESCs, and CD34+ cells were visible in the lesion on MR images as a hypointensive
      signal, persisting for more than 50 days. In rats with a balloon-induced spinal
      cord compression lesion, intravenously injected MSCs migrated to the lesion,
      leading to a hypointensive MRI signal. In plantar and Basso-Beattie-Bresnehan
      (BBB) tests, grafted animals scored better than lesioned animals injected with
      saline solution. Histologic studies confirmed a decrease in lesion size. We also
      used 3-D polymer constructs seeded with MSCs to bridge a spinal cord lesion. Our
      studies demonstrate that grafted adult as well as embryonic stem cells labeled
      with iron-oxide nanoparticles migrate into a lesion site in brain as well as in
      spinal cord.

PMID- 15965115
TI  - The miniature pig as an animal model in biomedical research.
AB  - Crucial prerequisites for the development of safe preclinical protocols in
      biomedical research are suitable animal models that would allow for human-related
      validation of valuable research information gathered from experimentation with
      lower mammals. In this sense, the miniature pig, sharing many physiological
      similarities with humans, offers several breeding and handling advantages (when
      compared to non-human primates), making it an optimal species for preclinical
      experimentation. The present review offers several examples taken from current
      research in the hope of convincing the reader that the porcine animal model has
      gained massively in importance in biomedical research during the last few years.
      The adduced examples are taken from the following fields of investigation: (a)
      the physiology of reproduction, where pig oocytes are being used to study
      chromosomal abnormalities (aneuploidy) in the adult human oocyte; (b) the
      generation of suitable organs for xenotransplantation using transgene expression
      in pig tissues; (c) the skin physiology and the treatment of skin defects using
      cell therapy-based approaches that take advantage of similarities between pig and
      human epidermis; and (d) neurotransplantation using porcine neural stem cells
      grafted into inbred miniature pigs as an alternative model to non-human primates
      xenografted with human cells.

PMID- 15965116
TI  - Graft/host relationships in the developing and regenerating CNS of mammals.
AB  - A new light was shed on the utility of neural grafts when it was recognized that
      donor tissues and cells offer more than a source of immature progenitors
      potentially capable of cell replacement: First, they have the inherent capacity
      to produce multiple trophic and tropic factors promoting cell survival and tissue
      plasticity often characteristic of the immature central nervous system (CNS).
      Second, by their interaction with the host microenvironment via cell/cell and
      cell/ECM interactions, these grafts are capable of re-establishing homeostasis,
      which can be, for example, reflected in rescue and protection of host elements
      from harmful influences. This second capacity of donor cells relies, in part,
      also on a "dormant" but still present regenerative capacity of mature or even
      aged CNS and on the possibility of its mobilization in the damaged nervous system
      by neural grafts. For this to occur efficiently after transplantation, a bi
      directional dialogue between donor and host cells must gradually be established,
      in which both "partners" transmit signals (cell/cell contact, molecular
      messengers), "listen to" and "understand" each other and are able to react by
      modifying their own plasticity- and development-related programs. Thus, for the
      best possible recovery of functionality in the injured adult and aged nervous
      system, neurotransplantation must always try to find optimal conditions for all
      three of the mentioned qualities of neural grafts, especially for the protection
      and/or reactivation of neural circuitry embedded in non-neurogenic CNS areas.
      Once fully understood, this newly recognized aspect of neurotransplantation (and
      topic of this review) might, someday, even allow the recovery of systems that
      would otherwise be doomed, such as cognition- and experience-related circuitry.

PMID- 15965117
TI  - Grafted neural stem cells shield the host environment from oxidative stress.
AB  - Here, we present our preliminary data showing that neural stem cells (NSCs) can
      prevent the degeneration of striatal neurons when transplanted into the CNS prior
      to intoxication with 3-nitropropionic acid (3-NP). In the adult CNS, the number
      of NSCs, a major source of neural cell populations and plasticity-modulating
      factors, is relatively low if compared to that of the developing brain. This,
      together with the adult growth-inhibitory environment, limits its regenerative
      capacity. Our recent observation has shown that grafted NSCs may rescue/protect
      neurons in the chronically impaired mesostriatal system. On the basis of this
      study and because we were also intrigued by our recent observations regarding the
      rescue/protective role of NSCs in vitro, we decided to test the hypothesis that
      grafted NSCs can also be deposited preventively in the CNS (and perhaps join the
      pool of endogenous NSCs of the intact host brain) for later buffering and
      maintenance of homeostasis when the host is exposed to oxidative stress.

PMID- 15965118
TI  - Administration of allogenic stem cells dosed to secure cardiogenesis and
      sustained infarct repair.
AB  - The mitotic capacity of heart muscle is too limited to fully substitute for cells
      lost following myocardial infarction. Emerging stem cell-based strategies have
      been proposed to overcome the self-renewal shortfall of native cardiomyocytes,
      yet there is limited evidence for their capability to achieve safe de novo
      cardiogenesis and repair. We present our recent experience in treating long-term,
      infarcted hearts with embryonic stem cells, a prototype source for allogenic cell
      therapy. The cardiogenic potential of the engrafted murine embryonic stem cell
      colony was pre-tested by in vitro differentiation, with derived cells positive
      for nuclear cardiac transcription factors, sarcomeric proteins and functional
      excitation-contraction coupling. Eight weeks after infarct, rats were randomized
      into sham- or embryonic stem cell-treated groups. Acellular sham controls or
      embryonic stem cells, engineered to express enhanced cyan fluorescent protein
      (ECFP) under control of the cardiac actin promoter, were injected through a 28
      gauge needle at three sites into the peri-infarct zone for serial assessment of
      functional and structural impact. In contrast to results with sham-treated
      animals, stem cell therapy yielded, over the 5-month follow-up period, new ECFP
      positive cardiomyocytes that integrated with the infarcted myocardium. The stem
      cell-treated group showed a stable contractile performance benefit with
      normalization of myocardial architecture post infarction. Transition of embryonic
      stem cells into cardiomyocytes required host signaling to support cardiac
      specific differentiation and could result in tumorigenesis if the stem cell dose
      exceeded the heart's cardioinductive capacity. Supported by the host environment,
      proper dosing and administration of embryonic stem cells is thus here shown
      useful in the chronic management of cardiac injury promoting sustained repair.

PMID- 15965120
TI  - A test for larval kin aggregations.

PMID- 15965119
TI  - Phytochrome B in the mesophyll delays flowering by suppressing FLOWERING LOCUS T
      expression in Arabidopsis vascular bundles.
AB  - Light is one of the most important environmental factors that determine the
      timing of a plant's transition from the vegetative to reproductive, or flowering,
      phase. Not only daylength but also the spectrum of light greatly affect
      flowering. The shade of nearby vegetation reduces the ratio of red to far-red
      light and can trigger shade avoidance responses, including stem elongation and
      the acceleration of flowering. Phytochrome B (phyB) acts as a photoreceptor for
      this response. Physiological studies have suggested that leaves can perceive and
      respond to shade. However, little is known about the mechanisms involved in the
      processing of light signals within leaves. In this study, we used an enhancer
      trap system to establish Arabidopsis thaliana transgenic lines that express phyB
      green fluorescent protein (GFP) fusion protein in tissue-specific manners. The
      analysis of these lines demonstrated that phyB-GFP in mesophyll cells affected
      flowering, whereas phyB-GFP in vascular bundles did not. Furthermore, mesophyll
      phyB-GFP suppressed the expression of a key flowering regulator, FLOWERING LOCUS
      T, in the vascular bundles of cotyledons. Hence, a novel intertissue signaling
      from mesophyll to vascular bundles is revealed as a critical step for the
      regulation of flowering by phyB.

PMID- 15965121
TI  - Effects of hypoxia and hypercapnic hypoxia on the localization and the
      elimination of Vibrio campbellii in Litopenaeus vannamei, the Pacific white
      shrimp.
AB  - Low oxygen (hypoxia) and elevated CO2 (hypercapnia, are characteristic of
      estuarine environments. Although hypoxia and hypercapnic hypoxia decrease the
      resistance of shrimp to bacterial pathogens, their direct effects on the immune
      system are unknown. Here we present evidence demonstrating in the penaeid shrimp
      Litopenaeus vannamei that both hypoxia and hypercapnic hypoxia affect the
      localization of bacteria, their conversion from culturable to non-culturable
      status (bacteriostasis), and their elimination from hemolymph and selected
      tissues. Shrimp were injected with a sublethal dose of a pathogenic strain of
      Vibrio campbellii expressing green fluorescent protein and resistance to
      kanamycin. Real-time polymerase chain reaction was used to determine the number
      of intact V. campbellii in hemolymph, gills, hepatopancreas, heart, and lymphoid
      organ. Selective plating was used to quantify the injected bacteria that remained
      culturable. We found that both hypercapnic hypoxia and hypoxia increased the
      percentage of culturable bacteria recovered from the hemolymph and tissues,
      suggesting an overall decrease in bacteriostatic activity. Hypoxia and
      hypercapnic hypoxia generally increased the distribution of intact V. campbellii
      to the hepatopancreas and the gills, which are major targets for the pathogenic
      effects of Vibrio spp., without affecting the number of intact bacteria in the
      lymphoid organ, a main site of bacterial accumulation and bacteriostatic
      activity.

PMID- 15965122
TI  - Anti-tubulin labeling reveals ampullary neuron ciliary bundles in opisthobranch
      larvae and a new putative neural structure associated with the apical ganglion.
AB  - This investigation examines tubulin labeling associated with the apical ganglion
      in a variety of planktotrophic and lecithotrophic opisthobranch larvae. Emphasis
      is on the ampullary neurons, in which ciliary bundles within the ampulla are
      strongly labeled. The larvae of all but one species have five ampullary neurons
      and their associated ciliary bundles. The anaspid Phyllaplysia taylori, a species
      with direct development and an encapsulated veliger stage, has only four
      ampullary neurons. The cilia-containing ampulla extends to the pretrochal surface
      via a long, narrow canal that opens to the external environment through a very
      small pore (0.1 microm diameter). Cilia within the canal were never observed to
      project beyond the opening of the apical pore. The ampullary canals extend toward
      and are grouped with the ciliary tuft cells and remain in this location as
      planktotrophic larvae feed and grow. If, as has been reported, the ciliary tuft
      is motile, the pores may be continually bathed in fresh seawater. Such an
      arrangement would increase sensitivity to environmental chemical stimuli if the
      suggested chemosensory function of these neurons is correct. In general, ciliary
      bundles of newly hatched veligers are smaller in planktotrophic larvae than in
      lecithotrophic larvae. In planktotrophic larvae of Melibe leonina, the ciliary
      bundles increase in length and width as the veligers feed and grow. This may be
      related to an increase in sensitivity for whatever sensory function these neurons
      fulfill. An unexpected tubulin-labeled structure, tentatively called the apical
      nerve, was also found to be associated with the apical ganglion. This putative
      nerve extends from the region of the visceral organs to a position either within
      or adjacent to the apical ganglion. One function of the apical nerve might be to
      convey the stimulus resulting from metamorphic induction to the visceral organs.

PMID- 15965123
TI  - Exploration in a T-maze by the crayfish Cherax destructor suggests bilateral
      comparison of antennal tactile information.
AB  - Many crayfish species inhabit murky waters or have a crepuscular lifestyle, which
      forces them to rely on chemical and mechanical information rather than visual
      input. Information on how they use one form of mechanical information-tactile
      cues-to explore their local environment is limited. We observed the exploratory
      behavior of the crayfish Cherax destructor in a T-maze under red light. Animals
      moved forward along the long arm of the maze and then moved equally in one of two
      available directions. The arm chosen by one crayfish did not affect that selected
      by a second crayfish tested immediately after in an unwashed maze. Previous
      experience in the maze also did not affect the choice. We found, however, that
      crayfish with one antenna denervated or splinted back to the carapace turned more
      often toward the unaltered side. Our data support the hypothesis that crayfish
      bilaterally compare information from their antennae.

PMID- 15965124
TI  - Cell differentiation is a primary growth process in developing limbs of Artemia.
AB  - The limb of the brine shrimp Artemia develops over a four-instar period when the
      protopod, endite, exopod, endopod, and epipod are defined and cell
      differentiation (change in cell shape) occurs. To understand the importance of
      cell differentiation in limb growth, development of the epidermis was studied in
      the first thoracopod of instar V-VIII larvae. Each region was established by
      instar V, and the larval epidermal cells developed into general epidermal (GEC),
      tendinal, setal, or transport cells by instar VI. Basal extensions of the GECs
      formed pillar structures. The epidermal cells decreased in height from 10 to 4
      microm by instar VI. Increase in length and width resulted from both cell
      replication and expansion of the apical cell surface in differentiating cells.
      Growth occurred mainly by cell replication in instar V, whereas expansion of the
      cell surface in GEC and setae was the major growth process in instar VII.
      Increase in apical cell surface area occurred primarily by change in cell shape
      from columnar to squamous during instar V and by increase in total cell surface
      in subsequent instars. The results demonstrated that cell differentiation is a
      significant component of growth during limb development.

PMID- 15965125
TI  - Gill anatomy and the evolution of symbiosis in the bivalve family Thyasiridae.
AB  - Among families of bivalves with chemoautotrophic symbionts, the Thyasiridae may
      vary the most in their anatomical characters and in the extent of their
      nutritional reliance upon symbionts. Since only a fraction of thyasirid species
      are symbiotic, and the symbionts are mostly observed to be extracellular, this
      group may be representative of early stages in the evolution of bacterium-
      bivalve symbioses. To better understand the distribution of symbiosis among
      thyasirid genera, and the relationships between gill structure and symbiont
      occurrence, the gills of 26 thyasirid species were studied by light and electron
      microscopy. Observations revealed three gill types, which are generally
      constrained within genera or subgenera. Symbionts were found in two gill types:
      the most simple, homorhabdic filibranch morphotype, and the most derived and
      thickened morphotype, which resembles the gill structure of other chemosymbiotic
      bivalves. In all observable cases, the symbionts were located extracellularly
      among the microvilli of the bacteriocytes. Among individuals of the species
      Thyasira (Parathyasira) equalis, the quantity of symbionts varied. The results
      suggest an evolutionary sequence: a homorhabdic filibranch gill structure with
      few symbionts among the epithelial cell microvilli eventually thickened
      abfrontally, and thereby offered a larger surface for colonization by symbionts.
      Eventually, the symbionts persisted and grew in vacuoles within epithelial cells.

PMID- 15965126
TI  - Holopelagic Poeobius meseres ("Poeobiidae," Annelida) is derived from benthic
      flabelligerid worms.
AB  - Phylogenetic relationships among and within the more than 70 recognized families
      of Annelida are poorly understood. In some cases, such as the monotypic
      Poeobiidae, derived morphology hinders the ability to find convincing
      synapomorphies that help elucidate evolutionary origins. In such cases, molecular
      data can be useful. Poeobiidae consists of the holopelagic polychaete Poeobius
      meseres, which is typically found in midwater depths off California.
      Morphologists have speculated that it is close to or within Flabelligeridae, but
      definitive evidence was lacking. Herein we use maximum likelihood phylogenetic
      reconstruction methods to examine the nuclear 18S rDNA (SSU) gene and the
      mitochondrial cytochrome b gene. Our results strongly support the hypothesis that
      P. meseres is a highly derived flabelligerid annelid closely related to
      Therochaeta. Thus, Poeobiidae is a junior synonym for Flabelligeridae. This
      result raises interesting questions about the evolution of the holopelagic P.
      meseres from a benthic ancestral flabelligerid.

PMID- 15965127
TI  - A new deepwater species of Stauromedusae, Lucernaria janetae (Cnidaria,
      Staurozoa, Lucernariidae), and a preliminary investigation of stauromedusan
      phylogeny based on nuclear and mitochondrial rDNA data.
AB  - The deepwater stauromedusan Lucernaria janetae n. sp is described from adult and
      juvenile specimens collected from the East Pacific Rise. Lucernaria janetae is
      the first species in the genus recorded from the Pacific Ocean, and differs from
      its congeners in size and morphology. Mitochondrial (16S) and nuclear (SSU)
      ribosomal gene sequences from L. janetae were analyzed with those of
      representative stauromedusan taxa to evaluate stauromedusan monophyly. Both genes
      recovered a strongly monophyletic Stauromedusae that is the sister group to all
      other medusozoans. Support of these hypotheses is robust to method of
      phylogenetic reconstruction and to outgroup selection, buttressing the argument
      that Stauromedusae should be recognized as the class Staurozoa. The molecular
      markers used here favor the same topology of relationships among our samples and
      clearly distinguished between two species, Haliclystus sanjuanensis and H.
      octoradiatus, that have been considered synonymous by many workers. A stable
      systematic framework for Stauromedusae appears achievable through comprehensive
      study of both morphological and sequence data.

PMID- 15965129
TI  - Health, science, and complexity.

PMID- 15965130
TI  - The physical environment and physical activity: moving from ecological
      associations to intervention evidence.

PMID- 15965131
TI  - Building environment to promote health.

PMID- 15965132
TI  - Social networks and health: it's time for an intervention trial.

PMID- 15965133
TI  - Why do friendships matter for survival?

PMID- 15965134
TI  - Psychosocial epidemiology, social structure, and ideology.

PMID- 15965135
TI  - Wealth and health: the need for more strategic public health research.
AB  - This article argues that public health researchers have often ignored the
      analysis of wealth in the quest to understand the social determinants of health.
      Wealth concentration and the inequities in wealth between and within countries
      are increasing. Despite this scare accurate data are available to assist the
      analysis of the health impact of this trend. Improved data collection on wealth
      distribution should be encouraged. Epidemiologists and political economy of
      health researchers should pay more attention to understanding the dynamics of
      wealth and its consequences for population health. Policy research to underpin
      policies designed to reduce inequities in wealth distribution should be
      intensified.

PMID- 15965137
TI  - Cold periods and coronary events: an analysis of populations worldwide.
AB  - STUDY OBJECTIVE: To investigate the association between cold periods and coronary
      events, and the extent to which climate, sex, age, and previous cardiac history
      increase risk during cold weather. DESIGN: A hierarchical analyses of populations
      from the World Health Organisation's MONICA project. SETTING: Twenty four
      populations from the WHO's MONICA project, a 21 country register made between
      1980 and 1995. PATIENTS: People aged 35-64 years who had a coronary event. MAIN
      RESULTS: Daily rates of coronary events were correlated with the average
      temperature over the current and previous three days. In cold periods, coronary
      event rates increased more in populations living in warm climates than in
      populations living in cold climates, where the increases were slight. The
      increase was greater in women than in men, especially in warm climates. On
      average, the odds for women having an event in the cold periods were 1.07 higher
      than the odds for men (95% posterior interval: 1.03 to 1.11). The effects of cold
      periods were similar in those with and without a history of a previous myocardial
      infarction. CONCLUSIONS: Rates of coronary events increased during comparatively
      cold periods, especially in warm climates. The smaller increases in colder
      climates suggest that some events in warmer climates are preventable. It is
      suggested that people living in warm climates, particularly women, should keep
      warm on cold days.

PMID- 15965138
TI  - Multilevel modelling of built environment characteristics related to
      neighbourhood walking activity in older adults.
AB  - OBJECTIVE: To examine the relation between built environment factors
      (representing several dimensions of urban form of neighbourhoods) and walking
      activity at both the neighbourhood level and the resident level, in an older
      adult sample. DESIGN, SETTING, PARTICIPANTS: A cross sectional, multilevel design
      with neighbourhoods as the primary sampling unit and senior residents as the
      secondary unit. Five hundred and seventy seven residents (mean age = 74 years, SD
      = 6.3 years) participated in the survey, which was conducted among 56 city
      defined neighbourhoods in Portland, Oregon, USA. Neighbourhood level variables
      were constructed using geographical information systems. Resident level variables
      consisted of a mix of self reports and geocoded data on the built environment.
      MAIN OUTCOME MEASURE: Self reported neighbourhood walking. MAIN RESULTS: A
      positive relation was found between built environment factors (density of places
      of employment, household density, green and open spaces for recreation, number of
      street intersections) and walking activity at the neighbourhood level. At the
      resident level, perceptions of safety for walking and number of nearby
      recreational facilities were positively related to high levels of walking
      activity. A significant interaction was observed between number of street
      intersections and perceptions of safety from traffic. CONCLUSIONS: Certain
      neighbourhood built environment characteristics related to urban form were
      positively associated with walking activity in the neighbourhoods of senior
      residents. Public health promotion of walking activity/urban mobility and the
      design of interventions need to consider the contribution of neighbourhood level
      built environment influences.

PMID- 15965139
TI  - High rates of ischaemic heart disease in Scotland are not explained by
      conventional risk factors.
AB  - STUDY OBJECTIVES: To (1) compare prevalence of socioeconomic, behavioural, and
      physiological ischaemic heart disease (IHD) risk factors in Scotland with a
      comparable nation (England) and (2) find out if their distribution explains
      Scotland's comparatively higher IHD rate (1.62 (1.30, 2.02)). DESIGN, SETTING,
      AND PARTICIPANTS: Cross sectional, individual level observational study with data
      on socioeconomic, behavioural, and physiological characteristics, 6064
      respondents from Scotland and England, (2362 and 3702 respectively), aged 45-74
      and with data on all required items. MAIN RESULTS: There were significant and
      meaningful differences between the Scottish and English in the prevalence of
      several IHD risk factors. However, a substantially and significantly higher risk
      of IHD persisted among the Scottish respondents (1.50 (1.17, 1.91)) despite
      control for a wide range of risk factors. CONCLUSIONS: Interpretation must be
      cautious because these are cross sectional data, however higher levels of
      conventional IHD risk factors contribute to but do not explain the comparatively
      high rates of IHD in Scotland. Alternative explanations for, and policy
      interventions to tackle, Scottish rates of IHD must be considered.

PMID- 15965140
TI  - Effects of neighbourhood socioeconomic status and convenience store concentration
      on individual level smoking.
AB  - OBJECTIVES: To assess the effects of neighbourhood level socioeconomic status
      (SES) and convenience store concentration on individual level smoking, after
      consideration of individual level characteristics. DESIGN: Individual
      sociodemographic characteristics and smoking were obtained from five cross
      sectional surveys (1979-1990). Participants' addresses were geocoded and linked
      with census data for measuring neighbourhood SES and with telephone yellow page
      listings for measuring convenience store concentration (density in a
      neighbourhood, distance between a participant's home and the nearest convenience
      store, and number of convenience stores within a one mile radius of a
      participant's home). The data were analysed with multilevel Poisson regression
      models. SETTING: 82 neighbourhoods in four northern California cities.
      PARTICIPANTS: 8121 women and men aged 25-74 from the Stanford heart disease
      prevention programme. MAIN RESULTS: Lower neighbourhood SES and higher
      convenience store concentration, measured by density and distance, were both
      significantly associated with higher level of individual smoking after taking
      individual characteristics into account. The association between convenience
      store density and individual smoking was modified by individual SES and
      neighbourhood SES. CONCLUSIONS: These findings are consistent with a growing body
      of literature suggesting that the socioeconomic and physical environments of
      neighbourhoods are associated with individual level smoking.

PMID- 15965141
TI  - Effect of social networks on 10 year survival in very old Australians: the
      Australian longitudinal study of aging.
AB  - STUDY OBJECTIVES: To examine if social networks with children, relatives,
      friends, and confidants predict survival in older Australians over 10 years after
      controlling for a range of demographic, health, and lifestyle variables. DESIGN:
      Prospective longitudinal cohort study (the Australian longitudinal study of
      aging) SETTING: Adelaide, South Australia. PARTICIPANTS: 1477 persons aged 70
      years or more living in the community and residential care facilities. MAIN
      RESULTS: After controlling for a range of demographic, health, and lifestyle
      variables, greater networks with friends were protective against mortality in the
      10 year follow up period. The hazard ratio for participants in the highest
      tertile of friends networks compared with participants in the lowest group was
      0.78 (95%CI 0.65 to 0.92). A smaller effect of greater networks with confidants
      (hazard ratio = 0.84; 95%CI = 0.71 to 0.98) was seen. The effects of social
      networks with children and relatives were not significant with respect to
      survival over the following decade. CONCLUSIONS: Survival time may be enhanced by
      strong social networks. Among older Australians, these may be important in
      lengthening survival.

PMID- 15965142
TI  - Psychosocial and physical work environment, and risk of pelvic pain in pregnancy.
      A study within the Danish national birth cohort.
AB  - OBJECTIVE: The sparse knowledge of the aetiology of pelvic pain in pregnancy
      makes evidence based prevention a limited option. The aim of this study was to
      examine the relation between pelvic pain in pregnancy and physical and
      psychosocial working conditions. METHODS: This study used self reported data on
      working conditions for 1219 cases and 1539 controls, sampled as a nested case
      control study within the Danish national birth cohort. Cases and controls were
      selected on the basis of self reported pelvic pain intensity, pain localisation,
      and pain impact on daily living activities. Exposure data were collected
      prospectively; early in pregnancy and before the onset of pelvic pain. Main
      outcome measures were odds ratios for pelvic pain in pregnancy as a function of
      physical and psychosocial working conditions. RESULTS: Pregnant women with fixed
      evening work and with rotating shifts (without night shift) had odds ratios for
      pelvic pain in pregnancy of 1.76 (95% confidence intervals 1.04 to 2.96) and 1.65
      (1.22 to 2.24), respectively, compared with women with day work. Physically
      strenuous work was associated with an almost 50% increased risk of pelvic pain in
      pregnancy (1.47; 1.17 to 1.84). In women who were under high psychosocial strain
      at work odds ratio was 1.39 (1.12 to 1.74) compared with women with low job
      strain. CONCLUSION: Both physically and psychosocially demanding working
      conditions, measured by physically strenuous work, rotating shifts, and high job
      strain, are associated with an increased reporting of pelvic pain in pregnancy.

PMID- 15965143
TI  - Mortality in children from influenza and respiratory syncytial virus.
AB  - STUDY OBJECTIVE: To quantify mortality attributable to influenza and respiratory
      syncytial virus (RSV) infection in children. DESIGN AND METHODS: Comparison of
      death rates (all cause and certified respiratory) in England over winters 1989/90
      to 1999/00 during and outside influenza and RSV circulation periods. Virus active
      weeks were defined from clinical and virological surveillance data. Excess deaths
      associated with weeks of either influenza or RSV activity over virus non-active
      weeks were estimated in each winter for age groups 1-12 months, 1-4, 5-9, and 10
      14 years. The estimate obtained was allotted to influenza and RSV in the
      proportion derived from independent separate calculations for each virus. MAIN
      RESULTS: Average winter respiratory deaths attributed to influenza in children 1
      month-14 years were 22 and to RSV 28; and all cause deaths to influenza 78 and to
      RSV 79. All cause RSV attributed deaths in infants 1-12 months exceeded those for
      influenza every year except 1989/90; the average RSV and influenza attributed
      death rates were 8.4 and 6.7 per 100 000 population respectively. Corresponding
      rates for children 1-4 years were 0.9 and 0.8 and for older children all rates
      were 0.2 or less, except for an influenza rate of 0.4 in children 10-14 years.
      CONCLUSIONS: Influenza and RSV account for similar numbers of deaths in children.
      The impact varies by winter and between age groups and is considerably
      underestimated if analysis is restricted to respiratory certified deaths. Summing
      the impact over the 11 winters studied, compared with influenza RSV is associated
      with more deaths in infants less than 12 months, almost equal numbers in children
      1-4 years, and fewer in older children. Improved information systems are needed
      to investigate paediatric deaths.

PMID- 15965144
TI  - Socioeconomic differences in childhood hospital inpatient service utilisation and
      costs: prospective cohort study.
AB  - STUDY OBJECTIVE: To examine the association between socioeconomic position at the
      time of birth and the use and cost of hospital inpatient services during the
      first 10 years of life. DESIGN: Analysis of a database of linked birth
      registrations, hospital records, and death certificates. Associations between the
      social class of the head of household and hospital inpatient service utilisation
      and costs during the first 10 years of life were analysed using multilevel
      multiple regression modelling. PARTICIPANTS AND SETTING: All 117 212 children
      born to women who both lived and delivered in hospital in Oxfordshire or West
      Berkshire, southern England, during the period 1 January 1979 to 31 December
      1988. MAIN RESULTS: The study showed that children born into social classes II,
      III-NM, III-M, IV, and V were more likely to be admitted to hospital, spend
      longer in hospital overall, and generate greater hospital costs than children
      born into social class I. The adjusted effect regarding hospital inpatient
      admissions, days, and costs was 1.27 (95% CI: 1.26, 1.27), 1.20 (1.19, 1.21), and
      1.50 (1.49, 1.53), respectively, for children born into social class V when
      compared with children born into social class I. The impact of social class on
      hospital inpatient admissions, days, and costs was most acutely felt during years
      3-10 of life as compared with the first two years of life. CONCLUSIONS: Health
      service decision makers need to be alert to the adverse sequelae that might
      result from socioeconomic disadvantage when planning health services for
      children. Particular attention should be paid to targeting deprived populations
      with prevention interventions that are known to be effective.

PMID- 15965145
TI  - Effect of psychiatric illness and labour market status on suicide: a healthy
      worker effect?
AB  - STUDY OBJECTIVE: To describe the association between labour market status and
      death by suicide with focus on admission with a psychiatric disorder. DESIGN:
      Nested case-control study. Data from routine registers. SETTING: Entire Danish
      population. PARTICIPANTS: 9011 people aged 25-60 years who committed suicide
      during 1982-1997 and 180 220 matched controls. MAIN RESULTS: In the general
      population, not being fully employed is associated with a twofold to threefold
      increased relative risk of death by suicide, compared with being fully employed.
      In contrast, fully employed people who have been first admitted to a psychiatric
      hospital within the past year are at increased suicide risk. Patients who are
      unemployed, social benefits recipients, disability pensioners, or otherwise
      marginalised on the labour market have a suicide risk of 0.60 (95% CI: 0.46 to
      0.78), 0.41 (0.23 to 0.74), 0.70 (0.45 to 1.08), and 0.86 (0.53 to 1.41),
      respectively. Although a similar risk decrease is found in women, men, people
      younger than 30 years, people older than 45 years, and in people who become
      unemployed, the reversed effect attenuates with time since admission, and little
      association is seen when a marginal structural model is applied. CONCLUSIONS:
      Although the results show an increased suicide mortality associated with
      unemployment and labour market marginalisation in the general population, the
      results suggest little or an inverse association between unemployment and suicide
      in people with psychiatric illness. The associations seen suggest the need to
      consider healthy worker selection effects when studying the causal pathway from
      unemployment and psychiatric illness to suicide.

PMID- 15965146
TI  - Uncovering neighbourhood influences on intimate partner violence using concept
      mapping.
AB  - While neighbourhood influences on the risk of intimate partner violence have been
      reported, this body of research has suffered from a lack of strong theoretical
      and conceptual guidance, and few studies have examined the potential pathways
      from neighbourhoods to intimate partner violence. This paper used concept mapping
      methods with 37 women who were residents of Baltimore City to obtain cluster maps
      representing the important neighbourhood domains that affect the prevalence,
      perpetration, severity, and cessation of intimate partner violence. Domains
      important for intimate partner severity and perpetration differed from those
      important for cessation of intimate partner violence. Finally, diagrams of the
      domains, drawn by the concept mapping participants, illustrated the pathways by
      which neighbourhood characteristics potentially influence intimate partner
      violence severity, perpetration, and cessation. These results can be used to
      generate testable hypotheses regarding neighbourhood influences on intimate
      partner violence in future quantitative research and to inform the design of
      public health intimate partner violence programmes.

PMID- 15965147
TI  - Assessing psychosocial/quality of life outcomes in screening: how do we do it
      better?

PMID- 15965148
TI  - The order is rapidly fadin'.

PMID- 15965149
TI  - Let green lead not astray.

PMID- 15965150
TI  - Vision restoration therapy: confounded by eye movements.

PMID- 15965151
TI  - Onchocerciasis: a potential risk factor for glaucoma.
AB  - BACKGROUND: Onchocerciasis is a microfilarial disease that causes ocular disease
      and blindness. Previous evidence of an association between onchocerciasis and
      glaucoma has been mixed. This study aims to further investigate the association
      between onchocerciasis and glaucoma. METHODS: All subjects were patients at the
      Bishop John Ackon Christian Eye Centre in Ghana, west Africa, undergoing either
      trabeculectomy for advanced glaucoma or extracapsular extraction for cataracts,
      who also had a skin snip biopsy for onchocerciasis. A cross sectional case
      control study was performed to assess the difference in onchocerciasis prevalence
      between the two study groups. RESULTS: The prevalence of onchocerciasis was 10.6%
      in those with glaucoma compared with 2.6% in those with cataracts (OR, 4.45 (95%
      CI 1.48 to 13.43)). The mean age in the glaucoma group was significantly younger
      than in the cataract group (59 and 65, respectively). The groups were not
      significantly different with respect to sex or region of residence. In models
      adjusted for age, region, and sex, subjects with glaucoma had over three times
      the odds of testing positive for onchocerciasis (OR, 3.50 (95% CI 1.10 to
      11.18)). CONCLUSIONS: This study has shown a positive association between
      subclinical onchocerciasis and glaucoma. This finding emphasises the importance
      of eradication of onchocerciasis from west Africa.

PMID- 15965152
TI  - Visual loss following removal of intraocular silicone oil.
AB  - AIM: To investigate the cause of visual loss following removal of intraocular
      silicone oil in patients who underwent vitrectomies for retinal detachment or
      giant retinal tear. METHODS: The clinical records of three cases with visual loss
      following removal of silicone oil were reviewed. Investigations carried out
      included fundus fluorescein angiogram, optical coherence tomography, and
      electrophysiological studies. RESULTS: Visual acuities dropped from 6/9 to 6/36
      in two cases and 6/24 to 3/24 in the third. None of the three cases had macula
      detachment at any stage. Fundus fluorescein angiogram and optical coherence
      tomography were normal in all cases. Pattern electroretinogram showed reduced
      amplitudes of the P50 and N95 components. Multifocal electroretinogram indicated
      a selective damage to the central part of the macula. CONCLUSIONS: The results
      suggest that the abnormality arises predominantly in the central part of the
      macula, especially the outer and middle layers. However, the exact mechanism
      still remains obscure.

PMID- 15965153
TI  - Decreased tear lipocalin concentration in patients with meibomian gland
      dysfunction.
AB  - BACKGROUND/AIM: Recent studies have demonstrated that tear lipocalin (TL) and
      phospholipids have a crucial role in maintaining tear film stability. The level
      of TL in patients with meibomian gland dysfunction (MGD) was examined and these
      data were correlated with the severity of their clinical disorder. METHODS: 12
      patients with obstructive MGD, 12 patients with seborrhoeic MGD, and 12 age
      matched normal control subjects participated in this study. 3 mul of unstimulated
      tears were collected with a micropipette from the inferior tear meniscus in the
      right eye of all subjects. Tear samples were fractionated by high performance
      liquid chromatography, and TL concentrations were assayed with a bicinchoninic
      acid technique. RESULTS: The mean concentration of TL in patients with
      obstructive and seborrhoeic MGD was significantly lower than in normal controls.
      TL concentration correlated positively with tear film break up time and
      negatively with fluorescein staining scores. CONCLUSION: These results suggest
      that TL deficiency may be a predisposing factor for the manifestation of symptoms
      in MGD.

PMID- 15965154
TI  - The use of low dose methotrexate in children with chronic anterior and
      intermediate uveitis.
AB  - AIM: To assess the efficacy of low dose methotrexate (MTX) therapy for children
      with chronic anterior and intermediate uveitis. METHODS: A retrospective case
      review of 10 children who received MTX for chronic uveitis at a tertiary referral
      centre was performed. The following data were recorded for each patient: age,
      sex, race, duration of uveitis, primary diagnosis, anatomical localisation of
      uveitis, corticosteroid therapy, dose range of MTX, duration of MTX therapy, and
      side effects of MTX therapy. Several clinical parameters were evaluated to study
      the effect of MTX. These included visual acuity, anterior chamber inflammation,
      and topical and oral corticosteroid requirement. RESULTS: After MTX VA of 6/6 or
      better was present in 100% right eyes and 80% left eyes (p = 0.055 and p = 0.016,
      respectively). Anterior chamber inflammation decreased in 60% of children after
      MTX (p = 0.0168). The requirement of topical steroid decreased from a mean of 5.6
      times a day before MTX to 1.5 times a day after MTX (p = 0.005). The dose of oral
      steroid decreased from a mean of 18 mg per day to 2.85 mg per day (p = 0.012).
      The most common adverse effect was nausea (20%). No patient required
      discontinuation of MTX because of side effects. CONCLUSION: MTX is effective and
      safe for chronic anterior and intermediate uveitis in children. An increase
      awareness of its efficacy is required among paediatricians and ophthalmologists
      to prevent sight threatening complication of chronic uveitis and its treatment
      with long term use of steroids.

PMID- 15965155
TI  - Intraocular pressure changes in the contralateral eye after trabeculectomy with
      mitomycin C.
AB  - AIM: To assess intraocular pressure (IOP) changes of the contralateral eyes of
      eyes undergoing trabeculectomy with mitomycin C (MMC). METHODS: Non-comparative
      retrospective study of 24 consecutive patients who underwent trabeculectomy with
      MMC that led to more than 45% reduction in IOP. In the contralateral eyes, IOP
      before surgery was compared with IOP 1 day and 1 month after surgery. 11 fellow
      eyes were under topical hypotensive therapy while 13 contralateral eyes were not
      (12 contralateral eyes had previous filtering surgery and one had normal tension
      glaucoma). No patients had systemic ocular hypotensive therapy. RESULTS: Mean IOP
      in all contralateral eyes decreased from 15.5 (SD 5.5) mm Hg to 12.5 (3.8) mm Hg
      (p<0.01), and 13.0 (4.7) mm Hg (p<0.001) 1 day and 1 month after surgery,
      respectively. In the 11 fellow eyes under topical ocular hypotensive therapy mean
      IOP was reduced from 19.5 (4.0) mm Hg to 13.5 (2.2) mm Hg (p<0.01), and 16.5
      (2.8) mm Hg (p<0.05) 1 day and 1 month after surgery, respectively. In the 13
      fellow eyes not under topical ocular hypotensive therapy mean IOP was reduced
      from 12.1 (4.2) mm Hg to 11.6 (4.7) mm Hg (p not significant) and 9.8 (3.8) mm Hg
      (p0.01) 1 day and 1 month after surgery, respectively. CONCLUSIONS: In the
      present population, a month after trabeculectomy, mean IOP in the contralateral
      eyes decreased independently of whether these contralateral eyes were undergoing
      topical ocular hypotensive therapy or not.

PMID- 15965156
TI  - The visual field in toxoplasmic retinochoroiditis.
AB  - AIMS: To document loss of central field in patients with scars from toxoplasmic
      retinochoroiditis close to the disc after resolution of disease. METHODS:
      Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled
      from four centres. Automated central visual field testing was performed when
      their disease had settled and retinal photographs of the lesions were taken. The
      type of central field defect (whether absolute or relative) and whether it broke
      out to the periphery were correlated with the size of the retinochoroidal scar
      and its proximity to the optic nerve head. RESULTS: 69 eyes were enrolled; 16
      (26%) were discarded because of poor field performance. Of the 53 remaining eyes,
      31 showed absolute defects and 20 relative defects. Scars within one disc
      diameter of the disc were more likely to be associated with absolute defects
      breaking out to the periphery. CONCLUSION: The scarring induced by toxoplasmic
      retinochoroiditis is associated with considerable field loss when it occurs close
      to the optic nerve head. Current treatment is unlikely to ameliorate this
      situation. The degree of visual field loss should be an outcome measure for
      future trials of the efficacy of treatment trials for the disease.

PMID- 15965157
TI  - The angiopoietin/Tie-2 system in proliferative sickle retinopathy: relation to
      vascular endothelial growth factor, its soluble receptor Flt-1 and von Willebrand
      factor, and to the effects of laser treatment.
AB  - AIM: To determine plasma levels of angiopoietin-1 and angiopoietin-2 (Ang-1, Ang
      2), their soluble receptor Tie-2, vascular endothelial growth factor (VEGF), its
      soluble receptor Flt-1 (as indices of angiogenesis), and von Willebrand factor
      (vWf, marking endothelial damage/dysfunction) in sickle cell disease (SCD)
      patients with proliferative sickle retinopathy (PSR), with non-proliferative
      retinopathy (NPR), or no retinopathy (NR) and in control subjects with normal
      haemoglobin (AA subjects). In addition, to determine changes with panretinal
      laser photocoagulation (PRP) therapy. METHODS: Research indices were measured
      (ELISA) in 24 SCD patients who had PSR, 16 with NPR, 16 with NR, and from 23 AA
      subjects. Eight patients received PRP therapy and plasma was obtained before
      laser treatment and at 6 months after the last PRP session. RESULTS: Ang-1, Ang
      2, VEGF, and vWf (but not Tie-2 or sFlt-1) were raised in SCD patients compared
      to AA subjects (p<0.01) but there were no differences among the three SCD
      subgroups. Significant correlations were between Ang-1 and VEGF, Ang-1 and Tie-2,
      and VEGF and sFlt-1 in patients with SCD (r = 0.67-0.88). Plasma Ang-2, VEGF,
      sFlt-1, and vWf levels did not change, but Ang-1 fell and Tie-2 rose
      significantly following PRP therapy. CONCLUSIONS: SCD patients have raised plasma
      angiopoietins (Ang-1, Ang-2), VEGF, and vWf compared to AA subjects. These
      indices did not differ according to severity of retinopathy and only limited
      changes occurred following PRP. The elevated growth factor levels in SCD may have
      obscured any association with retinopathy.

PMID- 15965158
TI  - Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients
      with ocular albinism with a novel mutation in the OA1 gene.
AB  - AIM: To perform genealogical and clinical studies in Finnish families with X
      linked ocular albinism (OA1), including characterisation of the potential
      misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs),
      and to determine the mutation behind the disease. METHODS: Three families with
      OA1 were clinically examined. VEFs were measured in two affected males and in one
      female carrier to characterise the cortical activation pattern after monocular
      visual stimulation. The neuronal sources of the VEFs were modelled with
      equivalent current dipoles (ECDs) in a spherical head model. All coding exons of
      the OA1 gene were screened for mutations by single strand conformation analysis
      and direct polymerase chain reaction sequencing. RESULTS: Genealogical studies
      revealed that the three families were all related. The affected males had foveal
      hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable
      nystagmus, iris transillumination, and hypopigmentation of the retinal pigment
      epithelium. The ECD locations corresponding to the VEFs revealed abnormal
      crossing of the optic fibres in both affected males, but not in the carrier
      female. A novel point mutation, leading to a STOP codon, was identified in the
      fifth exon of the OA1 gene. CONCLUSIONS: The data indicate that the novel
      mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the
      family studied. VEFs with ECD analysis was successfully used to demonstrate
      abnormal crossing of the optic fibres.

PMID- 15965159
TI  - Human extraocular muscles in mitochondrial diseases: comparing chronic
      progressive external ophthalmoplegia with Leber's hereditary optic neuropathy.
AB  - AIMS: To compare the ultrastructural aspects of human extraocular muscles in two
      types of mitochondrial disease: chronic progressive external ophthalmoplegia
      (CPEO) and Leber's hereditary optic neuropathy (LHON). METHODS: Muscle samples of
      the medial rectus obtained from surgery in a sporadic case of CPEO associated
      with deleted mitochondrial DNA, and post mortem in a case of 3460/ND1 LHON were
      processed for electron microscopy (EM). The medial rectus from an autoptic time
      to fixation matched control was used to exclude postmortem artefacts. RESULTS:
      The CPEO specimen revealed focal areas of disruption and abnormalities of
      mitochondria in some muscle fibres, creating a "mosaic-like" pattern. In the LHON
      specimen a diffuse increase in both number and size of mitochondria (mean
      diameter 0.85 mum v 0.65 mum of control, p<0.0001) with swollen appearance and
      disorganised cristae filled all spaces of sarcoplasmic reticulum. In some areas
      the excessive number of mitochondria slightly distorted myofibrils. CONCLUSION:
      EM investigation of extraocular muscles in CPEO and LHON reveals marked
      differences. A "mosaic-like" pattern caused by a selective damage of muscle
      fibres was evident in CPEO, whereas a diffuse increase in mitochondria with
      preservation of myofibrils characterised the LHON case. These ultrastructural
      changes may relate to the different expression of the two diseases, resulting in
      ophthalmoplegia in CPEO and normal eye movements in LHON.

PMID- 15965160
TI  - The effect of digital image resolution and compression on anterior eye imaging.
AB  - AIM: To determine the theoretical and clinical minimum image pixel resolution and
      maximum compression appropriate for anterior eye image storage. METHODS: Clinical
      images of the bulbar conjunctiva, palpebral conjunctiva, and corneal staining
      were taken at the maximum resolution of Nikon:CoolPix990 (2048x1360 pixels),
      DVC:1312C (1280x811), and JAI:CV-S3200 (767x569) single chip cameras and the
      JVC:KYF58 (767x569) three chip camera. The images were stored in TIFF format and
      further copies created with reduced resolution or compressed. The images were
      then ranked for clarity on a 15 inch monitor (resolution 1280 x 1024) by 20
      optometrists and analysed by objective image analysis grading. Theoretical
      calculation of the resolution necessary to detect the smallest objects of
      clinical interest was also conducted. RESULTS: Theoretical calculation suggested
      that the minimum resolution should be > or = 579 horizontal pixels at 25x
      magnification. Image quality was perceived subjectively as being reduced when the
      pixel resolution was lower than 767 x 569 (p<0.005) or the image was compressed
      as a BMP or <50% quality JPEG (p<0.005). Objective image analysis techniques were
      less susceptible to changes in image quality, particularly when using colour
      extraction techniques. CONCLUSION: It is appropriate to store anterior eye images
      at between 1280 x 811 and 767 x 569 pixel resolution and at up to 1:70 JPEG
      compression.

PMID- 15965161
TI  - The telomere of human chromosome 1p contains at least two independent autosomal
      dominant congenital cataract genes.
AB  - AIMS: Multiple genetic causes of congenital cataract have been identified, both
      as a component of syndromes and in families that present with isolated congenital
      cataract. Linkage analysis was used to map the genetic locus in a six generation
      Australian family presenting with total congenital cataract. METHODS:
      Microsatellite markers located across all known autosomal dominant congenital
      cataract loci were genotyped in all recruited family members of the Tasmanian
      family. Both two point and multipoint linkage analysis were used to assess each
      locus under an autosomal dominant model. RESULTS: Significant linkage was
      detected at the telomere of the p arm of chromosome 1, with a maximum two point
      LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an
      estimated location score of 5.61 at marker D1S507. Haplotype analysis places the
      gene inside a critical region between D1S228 and D1S199, a distance of
      approximately 6 megabases. The candidate gene PAX7 residing within the critical
      interval was excluded by direct sequencing in affected individuals. CONCLUSION:
      This is the third report of congenital cataract linkage to 1ptel. The critical
      region as defined by the shared haplotype in this family is clearly centromeric
      from the Volkmann cataract locus identified through study of a Danish family,
      indicating that two genes causing autosomal dominant congenital cataract map to
      the telomeric region of chromosome 1p.

PMID- 15965162
TI  - Knowledge and beliefs on corneal donation in Singapore adults.
AB  - AIM: To assess the knowledge and willingness of Singapore adults towards corneal
      donation. METHODS: The study population consists of a cluster random sample of
      the population living in Bedok North (an area in the eastern part of Singapore).
      The study population comprised residents aged 21-65 years living in 675 randomly
      sampled housing units. The participation rate was 65.9% (544/825). All
      participants were interviewed face to face with a questionnaire formulated
      according to the modified Horton and Horton model. Knowledge, values, attitudes,
      and spiritual beliefs of participants were assessed to evaluate their willingness
      to donate their corneas. RESULTS: 67.0% of participants were willing to donate
      their corneas. Ethnicity (Chinese) and religion (Christians, Hindus, or those
      with no religion) were associated with increased willingness to donate corneas.
      Greater knowledge and increased altruistic values were also associated with
      increased willingness to donate corneas. CONCLUSION: A proportion of participants
      were willing to donate their corneas. Awareness of corneal donation is high but
      specific knowledge should be further increased among adults.

PMID- 15965163
TI  - Histopathological and immunohistochemical studies of lenticules after
      epikeratoplasty for keratoconus.
AB  - AIMS: To examine histopathological and immunohistochemical changes in lenticules
      and host of corneal buttons from patients who previously underwent
      epikeratoplasty for keratoconus. METHODS: 12 penetrating keratoplasty specimens
      from patients with keratoconus who had previously undergone epikeratoplasty,
      eight keratoconus, and seven normal corneas were examined. Immunostaining for
      Sp1, alpha1-proteinase inhibitor (alpha1-PI), and alpha2-macroglobulin (alpha2M)
      were performed. RESULTS: In nine of the 12 lenticules, the keratoconus-like
      disruptions were found in Bowman's layer. Peripheral and posterior keratocyte
      repopulation of the lenticules was observed in all cases. Keratocyte repopulation
      in the anterior and mid-stromal regions of the lenticules appeared related to the
      time since epikeratoplasty. Sp1 nuclear staining of the basal and wing epithelial
      cells was more intense in lenticules and keratoconus corneas than in normal
      corneas. Lenticular, host, and keratoconus keratocytes showed positive Sp1
      staining, whereas staining was absent in normal corneas. Compared to normal
      corneas, alpha1-PI and alpha2M immunostaining was lower in the lenticules, host,
      and keratoconus specimens. CONCLUSIONS: The epithelial cells and keratocytes
      repopulated in the lenticules retain keratoconus-like biochemical abnormalities
      such as upregulation of Sp1 and downregulation of alpha1-PI and alpha2M. The
      authors speculate that both keratocytes and the corneal epithelium may
      participate in the development of keratoconus.

PMID- 15965164
TI  - A comparison of four methods of tonometry: method agreement and interobserver
      variability.
AB  - AIM: To compare the inter-method agreement in intraocular pressure (IOP)
      measurements made with four different tonometric methods. METHODS: IOP was
      measured with the Goldmann applanation tonometer (GAT), Tono-Pen XL, ocular blood
      flow tonograph (OBF), and Canon TX-10 non-contact tonometer (NCT) in a randomised
      order in one eye of each of 105 patients with ocular hypertension or glaucoma.
      Three measurements were made with each method, and by each of two independent GAT
      observers. GAT interobserver and tonometer inter-method agreement was assessed by
      the Bland-Altman method. The outcome measures were 95% limits of agreement for
      IOP measurements between GAT observers and between tonometric methods, and 95%
      confidence intervals for intra-session repeated measurements. RESULTS: The mean
      differences (bias) in IOP measurements were 0.4 mm Hg between GAT observers, and
      0.6 mm Hg, 0.1 mm Hg, and 0.7 mm Hg between GAT and Tono-Pen, OBF, and NCT,
      respectively. The 95% limits of agreement were smallest (bias +/-2.6 mm Hg)
      between GAT observers, and larger for agreement between the GAT and the Tono-Pen,
      OBF, and NCT (bias +/-6.7, +/-5.5, and +/-4.8 mm Hg, respectively). The OBF and
      NCT significantly underestimated GAT measurements at lower IOP and overestimated
      these at higher IOP. The repeatability coefficients for intra-session repeated
      measurement for each method were +/-2.2 mm Hg and +/-2.5 mm Hg for the GAT, +/
      4.3 mm Hg for the Tono-Pen, +/-3.7 mm Hg for the OBF, and +/-3.2 mm Hg for the
      NCT. CONCLUSIONS: There was good interobserver agreement with the GAT and
      moderate agreement between the NCT and GAT. The differences between the GAT and
      OBF and between the GAT and Tono-Pen probably preclude the OBF and Tono-Pen from
      routine clinical use as objective methods to measure IOP in normal adult eyes.

PMID- 15965165
TI  - The influence of central corneal thickness and age on intraocular pressure
      measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann
      applanation tonometry.
AB  - AIMS: To evaluate the influence of central corneal thickness (CCT) on intraocular
      pressure (IOP) measurements made with the Goldmann applanation tonometer (GAT),
      Tono-Pen XL, ocular blood flow tonograph (OBF), and Canon TX-10 non-contact
      tonometer (NCT). METHODS: CCT was recorded for either eye (randomly selected) of
      each of 105 untreated patients with ocular hypertension and glaucoma attending
      the glaucoma research unit at Moorfields Eye Hospital. For each of the selected
      eyes, IOP was measured with the GAT (two observers), Tono-Pen, OBF, and NCT in a
      randomised order. The relation of measured IOP and of inter-tonometer differences
      with CCT and subject age was explored by linear regression analysis. RESULTS: A
      significant association between measured IOP and CCT was found with each
      instrument. The change in measured IOP for a 10 mum increase in CCT was 0.28,
      0.31, 0.38, and 0.46 for the GAT, Tono-Pen, OBF, and NCT, respectively (all p< or
      = 0.05). There was a significant association between the NCT/GAT differences and
      CCT, with a tendency of NCT to overestimate GAT in eyes with thicker corneas.
      There was a significant association between GAT/Tono-Pen and OBF/Tono-Pen
      differences and age, with a tendency of GAT and OBF to overestimate the Tono-Pen
      in eyes of older subjects. CONCLUSION: IOP measurement by all four methods is
      affected by CCT. The NCT is affected by CCT significantly more than the GAT.
      Subject age has a differential effect on the IOP measurements made by the GAT and
      OBF compared to the Tono-Pen.

PMID- 15965166
TI  - Ahmed valve drainage implant surgery in the management of paediatric aphakic
      glaucoma.
AB  - BACKGROUND: Paediatric aphakic glaucoma presents months or years after cataract
      surgery in children and is a major long term complication. The results of
      surgical treatment are poor and many children require multiple and repeat
      procedures with poor visual outcomes. METHODS: 13 children (19 eyes) had Ahmed
      valve implantation surgery, nine of the children had previous procedures such as
      cycloablation or trabeculectomy. Mitomycin was used at surgery in some patients
      and valve needling with Healon GV and 5-fluorouracil in some blebs after surgery.
      SF(6) gas was also used at the time of surgery in most children to reform the
      anterior chamber. RESULTS: 12 of the children (18 eyes) achieved intraocular
      pressure control of 15 mm Hg or less with a valve alone or with additional
      medical therapy. CONCLUSION: Ahmed valve implantation surgery alone or in
      combination with medical therapy is successful and safe in the management of
      paediatric aphakic glaucoma.

PMID- 15965167
TI  - Outcomes in persistent hyperplastic primary vitreous.
AB  - AIMS: To report outcomes in cases of persistent hyperplastic primary vitreous
      (PHPV) and examine factors predictive of visual acuity in patients selected for
      surgery. METHODS: Retrospective case series of 55 eyes in 50 patients presenting
      between 1990 and 2001 at the Children's Hospital, Westmead. 33 eyes underwent
      surgery aimed at visual rehabilitation. RESULTS: In surgical patients, median age
      at surgery was 77 days, and median age at final follow up was 28 months. Six
      (18%) achieved a visual acuity at final follow up of 6/60 or better and eight
      (24%) achieved acuity of less than 6/60 to counting finger vision inclusive.
      Those undergoing surgery before 77 days were approximately 13 times more likely
      to obtain a visual acuity of counting fingers or better than those operated later
      (p = 0.01). Neither posterior segment PHPV nor post-surgical glaucoma was a
      significant predictor of outcome in this selected group. CONCLUSION: Early
      surgery aimed at rehabilitation markedly improves the likelihood of useful visual
      outcome in selected eyes with PHPV.

PMID- 15965168
TI  - "Light" versus "classic" laser treatment for clinically significant diabetic
      macular oedema.
AB  - AIM: To compare the effectiveness of "light" versus "classic" laser
      photocoagulation in diabetic patients with clinically significant macular oedema
      (CSMO). METHODS: A prospective randomised pilot clinical trial in which 29 eyes
      of 24 diabetic patients with mild to moderate non-proliferative diabetic
      retinopathy (NPDR) and CSMO were randomised to either "classic" or "light" Nd:YAG
      532 nm (frequency doubled) green laser. "Light" laser treatment differed from
      conventional ("classic") photocoagulation in that the energy employed was the
      lowest capable to produce barely visible burns at the level of the retinal
      pigment epithelium. Primary outcome measure was the change in foveal retinal
      thickness as measured by optical coherence tomography (OCT); secondary outcomes
      were the reduction/elimination of macular oedema on contact lens biomicroscopy
      and fluorescein angiography, change in visual acuity, contrast sensitivity, and
      mean deviation in the central 10 degrees visual field. Examiners were masked to
      patients' treatment. RESULTS: 14 eyes were assigned to "classic" and 15 were
      assigned to "light" laser treatment. At 12 months, seven (50%) of 14 eyes treated
      with "classic" and six (43%) of 14 eyes treated with "light" laser had a decrease
      of foveal retinal thickness on OCT (p = 0.79). A comparison of
      reduction/elimination of oedema, visual improvement, visual loss, change in
      contrast sensitivity, and mean deviation in the central 10 degrees showed no
      statistical difference between the groups at 12 months (p>0.05 for all groups).
      CONCLUSIONS: This study suggests that "light" photocoagulation for CSMO may be as
      effective as "classic" laser treatment, thus supporting the rationale for a
      larger equivalence trial.

PMID- 15965169
TI  - Serum prorenin levels and diabetic retinopathy in type 2 diabetes: new method to
      measure serum level of prorenin using antibody activating direct kinetic assay.
AB  - AIM: To investigate the serum levels of prorenin and its correlation with the
      severity of diabetic retinopathy (DR). METHODS: 248 patients with diabetes and
      108 control subjects were divided into four groups: no-DR (n = 146), no
      proliferative diabetic retinopathy (no-PDR) (n = 78), PDR (n = 24), and controls
      (n = 108). Serum levels of prorenin from all subjects were measured using the new
      antibody activating direct kinetic (AAD-PR) assay. The serum prorenin levels were
      compared among the groups. RESULTS: The serum levels of prorenin in the control,
      no-DR, no-PDR, and PDR groups, respectively, were 109.1 (66.1), 194.6 (160.4),
      271.5 (220.3), and 428.4 (358.4) pg/ml (mean (SD)). Prorenin in the PDR group was
      remarkably high compared with the control and no-DR groups (p<0.0001) and with
      the no-PDR group (p = 0.002). Serum levels of prorenin increased with
      increasingly severe retinopathy. No correlation was found between the prorenin
      level and the duration of disease or HbA(1c). CONCLUSIONS: The serum levels of
      prorenin in patients with PDR were found to be markedly high using the AAD-PR
      assay. Increased levels of prorenin in diabetes may have an important role in the
      pathogenesis of DR.

PMID- 15965170
TI  - Classification of abnormal fundus autofluorescence patterns in the junctional
      zone of geographic atrophy in patients with age related macular degeneration.
AB  - AIM: To describe and classify patterns of abnormal fundus autofluorescence (FAF)
      in the junctional zone of geographic atrophy (GA) in patients with age related
      macular degeneration. METHODS: Digital FAF images were recorded in 164 eyes of
      107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488
      nm, detection above 500 nm) as part of a prospective multicentre natural history
      study (FAM Study). FAF images were obtained in accordance with a standardised
      protocol for digital image acquisition and generation of mean images after
      automated alignment. RESULTS: Image quality was sufficient for classification of
      FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason
      for insufficient image quality. Abnormal FAF outside GA in 149 eyes was
      classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and
      diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone.
      In 4% there was no predominant pattern. The diffuse pattern was subdivided into
      four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%),
      and fine granular with peripheral punctate spots (6.7%). CONCLUSIONS: Different
      phenotypic patterns of abnormal FAF in the junctional zone of GA can be
      identified with cSLO FAF imaging. These distinct patterns may reflect
      heterogeneity at a cellular and molecular level in contrast with a non-specific
      ageing process. A refined phenotypic classification may be helpful to identify
      prognostic determinants for the spread of atrophy and visual loss, for
      identification of genetic risk factors as well as for the design of future
      interventional trials.

PMID- 15965171
TI  - Digital imaging of the optic nerve head: monoscopic and stereoscopic analysis.
AB  - AIMS: To compare monoscopic and stereoscopic assessment of the optic disc using
      novel software for the digital stereoscopic analysis of optic disc stereopairs.
      METHODS: Software was developed for the stereoscopic display of digital optic
      disc images using an interlaced display method. Neuroretinal rim width was
      determined at 10 degree intervals around the optic disc using a custom
      (stereoscopic) cursor whose depth was adjusted to that of Elschnig's rim.
      Measurements were taken, first viewing the disc monoscopically and at a separate
      sitting, stereoscopically. RESULTS: Measurements were made in 35 eyes from 35
      patients (1260 estimates for each observer) using three observers. The mean cup
      to disc ratio (CDR) ranged from 0.57 to 0.66 (SD 0.13-0.14) for monoscopic
      viewing compared with 0.64 to 0.69 (SD 0.12-0.14) for stereoscopic viewing.
      Stereoscopic assessments gave higher CDRs in temporal, superior, nasal, and
      inferior aspects of the optic disc (p<0.001, Mann-Whitney U test). Agreement
      between observers in estimating CDR was high for monoscopic assessment
      (intraclass correlation coefficient 0.74 (CI 0.72 to 0.76) increasing to 0.80
      (0.78 to 0.82) for stereoscopic assessment. CONCLUSION: Digital stereoscopic
      optic disc assessment provides lower estimates of neuroretinal rim width and
      higher levels of interobserver agreement compared with monoscopic assessments.

PMID- 15965172
TI  - Expression of growth differentiation factor-5 and bone morphogenic protein-7 in
      intraocular osseous metaplasia.
AB  - BACKGROUND/AIMS: Intraocular bone is seen in a wide spectrum of ocular disorders.
      The pathogenetic mechanisms of bone formation in the eye are unclear. Growth
      differentiation factor-5 (GDF-5), bone morphogenic protein-7 (BMP-7), and
      transforming growth factor beta-1 (TGF beta1) are multifunctional cytokines that
      have important roles in bone formation. Immunohistochemistry was used to localise
      GDF-5, BMP-7, and TGF beta1 in the human eye to determine their role in
      intraocular bone formation. METHODS: Paraffin embedded sections from human eyes
      included fetal eyes (n = 5), normal adult eyes (n = 4), eyes with osseous
      metaplasia (n = 8), and eyes with focal fibrous metaplasia of the retinal pigment
      epithelium (RPE) without osseous metaplasia (n = 2). Immunohistochemistry was
      performed using indirect immunofluorescence with antibodies to GDF-5, BMP-7, and
      TGF beta1. The staining intensity was evaluated semiquantitatively in the RPE,
      retina, ciliary epithelium, and cornea; and analysed statistically. RESULTS: When
      compared with normal adult eyes, which showed no RPE immunoreactivity, the RPE
      metaplasia surrounding areas of osseous metaplasia showed mild GDF-5 and moderate
      BMP-7 (p = 0.004) intracytoplasmic immunoreactivity. In contrast, trace GDF-5 and
      mild BMP-7 staining was seen in zones of RPE fibrous metaplasia in areas not
      associated with osseous metaplasia. Mild intracytoplasmic TGF beta1 expression
      was seen in the RPE metaplasia surrounding the bone when compared with adult
      eyes. Both fetal and adult eyes showed trace to mild GDF-5 and BMP-7 labelling of
      the non-pigmented ciliary epithelium which was increased in the eyes with osseous
      metaplasia. In eyes with osseous metaplasia, a significant decrease in GDF-5 and
      BMP-7 labelling was noted in fetal keratocytes (p = 0.0159 for both antibodies)
      when compared to adult eyes. Also, a significant decrease in BMP-7 labelling was
      seen in keratocytes in eyes with osseous metaplasia (p = 0.0162). CONCLUSIONS:
      The increase in GDF-5, BMP-7, and TGF beta1 immunoreactivity in zones of RPE
      metaplasia in eyes with osseous metaplasia suggests that these proteins have an
      important role in intraocular ectopic bone formation.

PMID- 15965173
TI  - The impact of the Health Technology Board for Scotland's grading model on
      referrals to ophthalmology services.
AB  - AIM: To ascertain the impact of the Health Technology Board for Scotland's
      grading model on referrals to ophthalmology services. METHODS: An analysis was
      performed of the screening outcomes of 5575 consecutive patients, who were
      screened by the Grampian Diabetic Retinopathy Screening Programme between March
      and September 2003 according to the recommendations of the Health Technology
      Board and the Scottish Diabetic Retinopathy Grading Scheme 2003. RESULTS: 3066
      (55%) were male. The median age was 65 years. 5.4% were passed on to the level 3
      grader and 3.4% were finally referred to ophthalmology services. 2.3% required re
      screening in 6 months; 85% were screened without mydriasis; 11.9% had ungradeable
      images despite a staged mydriasis protocol. Time to complete grading was 32 days
      (22-45). CONCLUSION: The impact of the Health Technology Board for Scotland's
      recommendations on referrals to ophthalmology services is modest and should be
      containable within existing resources.

PMID- 15965174
TI  - The effects of indocyanine green and endoillumination on rabbit retina: an
      electroretinographic and histological study.
AB  - AIM: To evaluate the functional and morphological retinal toxicity associated
      with intravitreal injection of indocyanine green (ICG) dye in rabbit eyes during
      vitrectomy with endoillumination. METHODS: 20 eyes of 10 New Zealand pigmented
      rabbits were used in the study. All eyes underwent pars plana vitrectomy and
      removal of posterior vitreous cortex under endoillumination. In one eye of each
      rabbit, intravitreal injection of 0.1 ml of 2.5 mg/ml ICG was applied for 30
      seconds followed by 10 minutes of endoillumination. The control eye had
      endoillumination only without ICG injection. Dark adapted and light adapted
      electroretinograms (ERGs) were performed before the surgery and 1 week after
      surgery for serial comparisons. Rabbits were killed 1 week after surgery and eyes
      were enucleated for histological examination. RESULTS: Serial ERG comparisons
      showed significant reduction in the light adapted a-wave amplitude (p = 0.037)
      and significant delays in the dark adapted and light adapted b-wave latencies (p
      = 0.020 and p = 0.038, respectively) in the ICG treated eyes. Histological
      examinations demonstrated loss of photoreceptor outer segments with focal absence
      of photoreceptors in some areas in the ICG injected eyes. CONCLUSIONS: Vitrectomy
      followed by intravitreal injection of 2.5 mg/ml ICG for 30 seconds with
      endoillumination may result in retinal toxicity causing functional and
      morphological retinal damages in rabbit eyes. The lowest concentration of ICG
      should be used if necessary for intraocular use to prevent potential retinal
      toxicity.

PMID- 15965175
TI  - Microglial stability and repopulation in the retina.
AB  - BACKGROUND/AIMS: Parenchymal central nervous system microglia are repopulated by
      bone marrow derived monocytes more slowly than any other reticuloendothelial
      cells. The contribution of bone marrow derived monocytes to the uninflammed
      retina has not been studied. The present study sought to determine repopulation
      of retinal microglia in uniflammed retina by bone marrow derived monocytes in
      bone marrow chimeric rats. METHODS: Chimeric (Y-->X) Lewis rats were constructed
      by transplanting 5 x 10(7) male bone marrow cells into lethally irradiated female
      recipient rats. The chimeras were sacrificed 8, 10, 12, 30, and 52 weeks after
      bone marrow transplant, and retina, brain, lung, and spleen samples were
      collected. DNA was extracted and quantified. Y positive infiltrating cells in the
      collected samples were detected by polymerase chain reaction amplification of a Y
      chromosome specific 104 bp fragment. RESULTS: There was a rapid repopulation of
      haematopoietic tissues in the spleen (at 8 weeks), confirming the establishment
      of chimerism, and to a lesser extent, of lung (at 30 weeks). This repopulation
      was absent in the brain parenchyma and retina until 52 weeks after
      transplantation. CONCLUSIONS: These data indicate that resident microglia in the
      retina, much like those in the brain, are stable in number in the retinal
      compartment (up to 1 year), and repopulation by bone marrow derived cells may be
      delayed for a year.

PMID- 15965178
TI  - Subconjunctival corticosteroid injection for the treatment of non-necrotising
      anterior scleritis.

PMID- 15965177
TI  - Generation of transgenic mice with mild and severe retinal neovascularisation.
AB  - AIM: To generate a mouse model for slow progressive retinal neovascularisation
      through vascular endothelial growth factor (VEGF) upregulation. METHODS:
      Transgenic mice were generated via microinjection of a DNA construct containing
      the human VEGF165 (hVEGF) gene driven by a truncated mouse rhodopsin promoter.
      Mouse eyes were characterised clinically and histologically and ocular hVEGF
      levels assayed by ELISA. RESULTS: One transgenic line expressing low hVEGF levels
      showed mild clinical changes such as focal fluorescein leakage, microaneurysms,
      venous tortuosity, capillary non-perfusion and minor neovascularisation, which
      remained stable up to 3 months postnatal. Histologically, there were some
      disturbance and thinning of inner and outer nuclear layers, with occasional focal
      areas of neovascularisation. By contrast, three other lines expressing high hVEGF
      levels presented with concomitantly severe phenotypes. In addition to the above,
      clinical features included extensive neovascularisation, haemorrhage, and retinal
      detachment; histologically, focal to extensive areas of neovascularisation
      associated with retinal folds, cell loss in the inner and outer nuclear layers,
      and partial retinal detachment were common. CONCLUSIONS: The authors generated
      four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from
      mild to severe neovascularisation. These models are a valuable research tool to
      study excess VEGF related molecular and cellular changes and provide additional
      opportunities to test anti-angiogenic therapies.

PMID- 15965176
TI  - TLRs and NODs mRNA expression pattern in healthy mouse eye.
AB  - AIMS: To look for TLR and NOD mRNA expression in the healthy eye and in other
      immune privileged and non-immune privileged mouse organs. METHODS:
      Semiquantitative RT-PCR was performed to look for TLR1-9 and NOD1 and NOD2 mRNA
      expressions in the whole eye, in the anterior (AP) and posterior (PP) portions of
      the eye, in corneal fibroblasts (CF) and in ovary, brain, testis, heart, lung,
      and spleen. RESULTS: All the TLR mRNAs were expressed in the whole eye of Balb/c
      mice. NIH and C57BL/6 did not express TLR9 and TLR8, respectively. NIH expressed
      higher levels of TLR1, 2, 3, and 6 than the other strains. C57BL/6 expressed the
      lowest levels of all TLRs. TLR9, 5, and 4 were the less expressed in all strains.
      All TLRs were expressed in Balb/c PP and TLR1 was not expressed in AP. In NIH and
      Balb/c CF the majority of TLRs were overexpressed with LPS. In testis, expression
      of most TLRs was absent. Non-immune privileged organs expressed most of the TLRs.
      All the organs expressed NOD1 and NOD2. In PP NOD2 was not expressed. CONCLUSION:
      TLRs and NODs are expressed in the eye, and could have an important role in the
      innate immunity.

PMID- 15965179
TI  - Visual field defect in association with chiasmal migration of intraocular
      silicone oil.

PMID- 15965180
TI  - Congenital hypertrophy of retinal pigment epithelium: a clinico-pathological case
      report.

PMID- 15965181
TI  - Finding malignant change in a necrotic choroidal melanocytoma: a clinical
      challenge.

PMID- 15965182
TI  - Improvement after transvitreal limited arteriovenous crossing manipulation
      without vitrectomy for complicated branch retinal vein occlusion using 25 gauge
      instrumentation.

PMID- 15965183
TI  - "Ecstasy" induced immunosuppression and herpes zoster ophthalmicus.

PMID- 15965184
TI  - Reversible posterior leucoencephalopathy syndrome: a cause of temporary cortical
      blindness.

PMID- 15965185
TI  - Morquio syndrome: electron microscopic findings.

PMID- 15965186
TI  - Importance of early morning intraocular pressure recording for measurement of
      diurnal variation of intraocular pressure.

PMID- 15965187
TI  - Autoimmune retinopathy associated with intravesical BCG therapy.

PMID- 15965188
TI  - Optical coherence tomography in photodynamic therapy.

PMID- 15965189
TI  - Preoperative videotape sessions and patient satisfaction with cataract surgery.

PMID- 15965190
TI  - Optical coherence tomography of the vitreomacular interface in photodynamic
      therapy.

PMID- 15965191
TI  - The national service framework for long term conditions: a novel approach for a
      "new style" NSF.

PMID- 15965193
TI  - Surgery for movement disorders: new applications?

PMID- 15965192
TI  - Cholinesterase inhibitors for treatment of dementia associated with Parkinson's
      disease.

PMID- 15965194
TI  - Ultrafast magnetic resonance imaging protocols in stroke.

PMID- 15965195
TI  - Molecular neurology of prion disease.
AB  - Prions are infectious pathogens principally composed of abnormal forms of a
      protein encoded in the host genome. They cause lethal neurodegenerative
      conditions including CJD, GSS, and kuru in humans and scrapie and bovine
      spongiform encephalopathy in domestic animals. Remarkably, distinct strains of
      prions occur despite absence of an agent-specific genome: misfolded proteins
      themselves may encode strain diversity--with wide implications in biology. The
      arrival of variant CJD, and the experimental confirmation that it is caused by
      infection with BSE-like prions, has focussed research on early diagnosis and
      treatment. Recent advances lead to considerable optimism that effective human
      therapies may now be developed. While several drugs have been tried in small
      numbers of patients, there is no clear evidence of efficacy of any agent and
      controlled clinical trials are urgently needed. Importantly, there is increasing
      recognition that fundamental processes involved in prion propagation--seeded
      aggregation of misfolded host proteins--are of far wider significance, not least
      in understanding the commoner neurodegenerative diseases that pose such a major
      and increasing challenge for healthcare in an ageing population.

PMID- 15965196
TI  - Qualitative neuropsychological performance characteristics in frontotemporal
      dementia and Alzheimer's disease.
AB  - BACKGROUND: Frontotemporal dementia (FTD) and Alzheimer's disease are clinically
      distinct disorders, yet neuropsychological studies have had variable success in
      distinguishing them. A possible reason is that studies typically rely on overall
      accuracy scores, which may obscure differences in reasons for failure.
      OBJECTIVES: To explore the hypothesis that analysis of qualitative performance
      characteristics and error types, in addition to overall numerical scores, would
      enhance the neuropsychological distinction between FTD and Alzheimer's disease.
      METHODS: 38 patients with FTD and 73 with Alzheimer's disease underwent
      assessment of language, visuospatial abilities, memory, and executive function,
      using a neuropsychological screening instrument and standard neuropsychological
      tests. In each of these cognitive domains, performance characteristics and error
      types were documented, in addition to numerical scores on tests. RESULTS: Whereas
      comparison of neuropsychological test scores revealed some group differences,
      these did not occur consistently across tests within cognitive domains. However,
      analysis of performance characteristics and error types revealed qualitative
      differences between the two groups. In particular, FTD patients displayed
      features associated with frontal lobe dysfunction, such as concrete thought,
      perseveration, confabulation, and poor organisation, which disrupted performance
      across the range of neuropsychological tests. CONCLUSIONS: Numerical scores on
      neuropsychological tests alone are of limited value in differentiating FTD and
      Alzheimer's disease, but performance characteristics and error types enhance the
      distinction between the two disorders. FTD is associated with a profound
      behavioural syndrome that affects performance on cognitive assessment, obscuring
      group differences. Qualitative information should be included in
      neuropsychological research and clinical assessments.

PMID- 15965197
TI  - Is there a relation between APOE expression and brain amyloid load in Alzheimer's
      disease?
AB  - BACKGROUND: It has been proposed that, independent of the epsilon4 allele, APOE
      promoter polymorphisms (-491 A/T and -219 G/T) may be risks factor for
      Alzheimer's disease by modulating APOE expression. OBJECTIVE: To measure the
      level of APOE expression in Alzheimer's disease. METHODS: Brains were obtained at
      necropsy from 114 patients with early and late onset sporadic Alzheimer's disease
      in Greater Manchester (UK) during years 1986 to 2001. Total RNA was extracted
      from 84 brains. Purified lymphocytes were obtained from fresh blood from 16
      probable Alzheimer cases from Lille (France). APOE and beta-actin gene expression
      was determined by reverse transcriptase polymerase chain reaction in brain and
      lymphocytes. RESULTS: An inverse correlation between APOE expression level and A
      beta loads was observed. As previously described and extended to 114 cases here,
      an association between the -219 TT genotype and a higher level of parenchymal A
      beta deposition was found, irrespective of APOE epsilon4 allele status. This
      effect was more pronounced in older individuals, whereas higher A beta load
      appeared more closely related to epsilon4 in the younger age group (cut off point
      at the median age at death (72.5 years)). The -219 TT genotype was associated
      with a decrease in APOE expression. There was a 60% decrease in APOE expression
      in lymphocytes from probable Alzheimer cases v controls (p = 0.01). CONCLUSIONS:
      In the oldest individuals, reduced APOE expression, modulated in part by -219 G/T
      polymorphism, may influence risk and constitute a determinant A beta load in
      Alzheimer's disease.

PMID- 15965198
TI  - Donepezil for dementia in Parkinson's disease: a randomised, double blind,
      placebo controlled, crossover study.
AB  - OBJECTIVE: To study the safety and efficacy of a cholinesterase inhibitor,
      donepezil hydrochloride, for the treatment of dementia in Parkinson's disease
      (PD). METHODS: This was a randomised double blind, placebo controlled, crossover
      study in 22 subjects with PD and dementia. Participants were randomised to
      receive either donepezil followed by identical placebo, or placebo followed by
      donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10
      weeks with a washout period of 6 weeks between the two periods. The primary
      outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale
      (ADAScog). RESULTS: Donepezil was well tolerated and most adverse events were
      mild. There was no worsening of PD symptoms as measured by the total or motor
      sections of the Unified Parkinson's Disease Rating Scale.There was a 1.9 point
      trend toward better scores on the ADAScog on treatment compared with placebo that
      was not statistically significant. The secondary cognitive measures showed a
      statistically significant 2 point benefit on the Mini Mental Status Examination
      and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global
      Impression of Change (CGI) showed a significant 0.37 point improvement on
      donepezil. No improvement was observed on the MDRS or the Brief Psychiatric
      Rating Scale. Carryover between treatment periods was observed but was not
      statistically significant. CONCLUSIONS: Donepezil was well tolerated and did not
      worsen PD. There may be a modest benefit on aspects of cognitive function. The
      possible clinical benefit measured by CGI was reflected in only one of the
      cognitive scales used in this study.

PMID- 15965200
TI  - Progression and prognosis in pure autonomic failure (PAF): comparison with
      multiple system atrophy.
AB  - OBJECTIVE: To clarify the progression of autonomic symptoms and functional
      deterioration in pure autonomic failure (PAF), particularly in comparison with
      multiple system atrophy (MSA). METHODS: The investigation involved eight patients
      with PAF (M/F = 7/1; mean age at onset, 57 years) and 22 with probable MSA
      matched for age at onset (M/F = 14/8; onset 56 years). Subjects were followed up
      for neurological symptoms, activities of daily living, and autonomic function for
      more than seven years. Autonomic functional tests were carried out. RESULTS: In
      PAF, fainting or sudomotor dysfunction occurred first, followed by constipation
      and syncope. Urinary dysfunction developed late, and respiratory dysfunction was
      not evident. This clinical course contrasted sharply with that in MSA, where
      early urinary dysfunction usually proceeded to sudomotor dysfunction or
      orthostatic hypotension (p = 0.004), followed by respiratory dysfunction (p =
      0.0004). Results of pharmacological tests also distinguished PAF from MSA.
      Progression and prognosis in patients with PAF did not worsen, unlike the steady
      progressive autonomic dysfunction in MSA (p < 0.0001, p < 0.0001, p = 0.0009, and
      p = 0.003, for progression to modified Rankin scale grade III, IV, V, and death,
      respectively). CONCLUSIONS: The time course and pattern of progression of
      autonomic failure differed significantly between PAF and MSA. Patients with PAF
      had slower functional deterioration and a better prognosis.

PMID- 15965199
TI  - The role of dominant striatum in language: a study using intraoperative
      electrical stimulations.
AB  - BACKGROUND: The role of the striatum in language remains poorly understood.
      Intraoperative electrical stimulation during surgery for tumours involving the
      caudate nucleus or putamen in the dominant hemisphere might be illuminating.
      OBJECTIVES: To study the role of these structures in language, with the aim of
      avoiding postoperative definitive aphasia. METHODS: 11 patients with cortico
      subcortical low grade gliomas were operated on while awake, and striatal
      functional mapping was done. Intraoperative direct electrical stimulation was
      used while the patients carried out motor and naming tasks during the resection.
      RESULTS: In five cases of glioma involving the dominant putamen, stimulations
      induced anarthria, while in six cases of glioma involving the dominant caudate,
      stimulations elicited perseveration. There was no motor effect. The striatum was
      systematically preserved. Postoperatively, all patients except one had transient
      dysphasia which resolved within three months. CONCLUSIONS: There appear to be two
      separate basal ganglia systems in language, one mediated by the putamen which
      might have a motor role, and one by the caudate which might have a role in
      cognitive control. These findings could have implications for surgical strategy
      in lesions involving the dominant striatum.

PMID- 15965201
TI  - Disturbances of grip force behaviour in focal hand dystonia: evidence for a
      generalised impairment of sensory-motor integration?
AB  - BACKGROUND: Focal task specific dystonia occurs preferentially during performance
      of a specific task. There may be an inefficiently high grip force when doing
      manipulative tasks other than the trigger task, possibly reflecting a generalised
      impairment of sensory-motor integration. OBJECTIVE: To examine how well subjects
      with writer's cramp (n = 4) or musician's cramp (n = 5) adapted their grip force
      when lifting a new object or catching a weight. METHODS: Nine patients with focal
      hand dystonia and 10 controls were studied. Experiments addressed different motor
      behaviours: (A) lifting and holding an object; (B) adjusting grip force in
      anticipation of or in reaction to a change in load force by catching a small
      weight dropped expectedly or unexpectedly into a hand held receptacle. RESULTS:
      In (A), patients produced a grip force overshoot during the initial lifts; force
      overflow was most pronounced in those with writer's cramp. Patients and controls
      adjusted their grip force to object weight within one or two lifts, though
      patients settled to a steady force level above normal. In (B), patients with
      focal hand dystonia and normal controls showed similar predictive grip force
      adjustments to expected changes in object load, suggesting that this aspect of
      sensory-motor integration was normal. Patients had a shorter latency of grip
      force response than controls after an unexpected load increase, reflecting either
      a greater level of preparatory motor activity or a disinhibited spinal reflex
      response. CONCLUSIONS: The overall increased grip force in patients with focal
      hand dystonia is likely to be a prelearned phenomenon rather than a primary
      disorder of sensory-motor integration.

PMID- 15965202
TI  - HIV leucoencephalopathy and TNFalpha expression in neurones.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) leucoencephalopathy (HIVL) is an
      uncommon and rapidly progressive form of AIDS dementia complex (ADC) that has
      remained poorly understood. Tumour necrosis factor alpha (TNFalpha), which has
      been implicated in the pathogenesis of ADC, is predominantly localised in
      macrophages in the HIV infected brain, although in vitro studies indicate that
      neurones can express this cytokine. OBJECTIVE: To examine the
      clinical/neuroradiological features of HIVL and the expression of TNFalpha in
      HIVL. METHODS: Six patients who presented with rapidly progressive dementia
      within four to 12 weeks of the primary manifestation of their HIV infection were
      evaluated. Clinical history, treatment regimens, and imaging studies were
      reviewed, and brain samples from three of the patients were studied by means of
      immunohistochemistry. RESULTS: Imaging studies showed diffuse bilateral deep
      white matter changes in all six patients. Clinical and imaging abnormalities
      improved in five of the six patients within weeks after initiation of
      antiretroviral treatment. Brain biopsies of two showed pronounced
      microglia/macrophage activation, but only scant viral protein (gp41) expression.
      Staining for TNFalpha was found in microglia/macrophages, and surprisingly, in
      neurones also. Postmortem analysis of a third patient also showed TNFalpha
      expression in neurones of the frontal cortex and basal ganglia. CONCLUSION: This
      study provides the first demonstration of staining for TNFalpha in the neurones
      of the HIV infected brain, and suggests that the process underlying this rapidly
      progressive form of ADC may reflect indirect mechanisms mediated by host factors,
      particularly TNFalpha.

PMID- 15965203
TI  - Objective B wave analysis in 55 patients with non-communicating and communicating
      hydrocephalus.
AB  - BACKGROUND: B waves, slow and rhythmic oscillations in intracranial pressure
      (ICP), are claimed to be one of the best predictors of outcome after surgery for
      normal pressure hydrocephalus (NPH). OBJECT: To determine the relation between
      the percentage of B waves and outcome in patients with hydrocephalus, and also
      the diurnal variation of B waves. METHODS: ICP and patient behaviour were
      recorded overnight (17 to 26 hours) in 29 patients with non-communicating
      hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude
      threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the
      percentage of total monitoring time (% B waves) using a computer algorithm, and
      correlated with postoperative outcome, defined as changes in 12 standardised
      symptoms and signs. RESULTS: There was no linear correlation between improvement
      after surgery in the 55 patients and total % B waves, but a correlation was found
      between improvement and % B waves during sleep (r = 0.39, p = 0.04). The
      percentage of B waves was the same during sleep and wakefulness, and patients
      with NPH had the same proportion of B waves as the non-communicating patients.
      CONCLUSIONS: B waves are commonly observed in patients with both communicating
      and non-communicating hydrocephalus, but are only weakly related to the degree of
      postsurgical improvement.

PMID- 15965205
TI  - Surgical management of tuberculum sellae meningiomas: involvement of the optic
      canal and visual outcome.
AB  - OBJECTIVE: To present a large series of surgically treated tuberculum sellae
      meningiomas with particular regard to involvement of the optic canal and visual
      outcome. METHODS: A retrospective analysis was done on 53 patients (40 female)
      with meningiomas originating from the tuberculum sellae who underwent surgery
      between 1991 and 2002. The standard surgical approach consisted of pterional
      craniotomy. Sixteen meningiomas extended posteriorly onto the diaphragma sella,
      29 anteriorly to the planum sphenoidale, and 19 to the anterior clinoid process.
      Thirty seven tumours involved the optic canal, three bilaterally. Follow up
      ranged from 6 to 108 months (mean 29.9 months). RESULTS: Total macroscopic
      resection was achieved in 48 patients. Median tumour size was 2.6 cm.
      Postoperatively, visual acuity improved in 20 patients and deteriorated in seven.
      Preoperative and postoperative visual acuity worsened with increasing duration of
      preoperative symptoms and with increasing age. Extension into the intraconal
      space was a negative predictor. However, tumour size did not influence visual
      acuity. Recurrence occurred in two cases (21 and 69 months postoperatively). Two
      patients died from causes unrelated to the tumour. CONCLUSIONS: In the majority
      of patients with tuberculum sellae meningiomas, total resection may be achieved
      through a pterional approach with minimal complications.

PMID- 15965204
TI  - Lateral transmuscular or combined interlaminar/paraisthmic approach to lateral
      lumbar disc herniation? A comparative clinical series of 48 patients.
AB  - BACKGROUND: The optimum operative technique for lateral lumbar disc herniations
      (LLDH) remains unclear, and both interlaminar and extraspinal approaches are
      used. OBJECTIVE: To compare outcome after LLDH removal either by a lateral
      transmuscular approach (LTM) or by a combined interlaminar and paraisthmic
      approach (CIP). METHODS: 28 patients underwent surgery using CIP and 20 using
      LTM. All patients were operated on by the same neurosurgeon. The clinical
      presentation of the two groups was comparable. Overall outcome was assessed after
      a mean follow up period of between 19 and 37 months using the Ebeling
      classification. In addition, the effect of surgery on radicular pain, low back
      pain, and sensory and motor deficits was defined. RESULTS: Excellent to good
      results were achieved in 95% of the LTM group and 57% of the CIP group. The
      outcome was satisfactory to poor in 5% of the LTM and 43% of the CIP group
      (p<0.004). The percentage of sensorimotor deficit and of radicular pain
      improvement was higher in the LTM group. New low back pain was found exclusively
      in the CIP group (21%). The complication rate was 5% in the LTM group and 11% in
      the CIP group. CONCLUSIONS: The LTM approach achieves a better overall outcome
      and improvement in radiculopathy. The complication rate is lower with the
      transmuscular route and the risk of new low back pain is minimised. These results
      are likely to be attributable at least in part to the lesser invasiveness of the
      LTM approach.

PMID- 15965206
TI  - Bilateral first rib fractures due to tardive dystonia.

PMID- 15965207
TI  - Traumatic brain injury and grey matter concentration: a preliminary voxel based
      morphometry study.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) studies have shown diffuse cerebral
      atrophy following traumatic brain injury. In the past, quantitative volumetric
      analysis of these changes was carried out by manually tracing specific regions of
      interest. In contrast, voxel based morphometry (VBM) is a fully automated
      technique that allows examination of the whole brain on a voxel by voxel basis.
      OBJECTIVE: To use VBM to evaluate changes in grey matter concentration following
      traumatic brain injury. METHODS: Nine patients with a history of traumatic brain
      injury (ranging from mild to severe) about one year previously were compared with
      nine age and sex matched healthy volunteers. T1 weighted three dimensional MRI
      images were acquired and then analysed with statistical parametric mapping
      software (SPM2). The patients with traumatic brain injury also completed
      cognitive testing to determine whether regional grey matter concentration
      correlated with a measure of attention and initial injury severity. RESULTS:
      Compared with controls, the brain injured patients had decreased grey matter
      concentration in multiple brain regions including frontal and temporal cortices,
      cingulate gyrus, subcortical grey matter, and the cerebellum. Decreased grey
      matter concentration correlated with lower scores on tests of attention and lower
      Glasgow coma scale scores. CONCLUSIONS: Using VBM, regions of decreased grey
      matter concentration were observed in subjects with traumatic brain injury
      compared with well matched controls. In the brain injured patients, there was a
      relation between grey matter concentration and attentional ability.

PMID- 15965208
TI  - Pallidal stimulation relieves myoclonus-dystonia syndrome.
AB  - A patient with myoclonus-dystonia syndrome was treated by implanting electrodes
      in the internal segment of the globus pallidus (GPi) and applying deep brain
      stimulation. Surgery was done in two sessions. The most affected limb was treated
      first and the other limb one year later. Neuronal recordings showed that most
      pallidal neurones discharged in bursts at a relatively low firing rate (mean
      (SD), 46 (18) Hz) compared with cells in the GPi in patients with Parkinson's
      disease. Neurones modified the rate and mode of discharge with dystonic postures
      and rapid involuntary contractions of limb muscles. Neurological examination at
      24 months after surgery showed a decline of 47.8% and 78.5% in the Burke-Fahn
      Marsden and disability rating scales, respectively.

PMID- 15965209
TI  - Tourette's syndrome and deep brain stimulation.
AB  - In this prospective double blind randomised "N of 1" study, a patient with a
      severe form of Tourette's syndrome was treated with bilateral high frequency
      stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus,
      the internal part of the globus pallidus (GPi), or both. Stimulation of either
      target improved tic severity by 70%, markedly ameliorated coprolalia, and
      eliminated self injuries. Severe forms of Tourette's syndrome may benefit from
      stimulation of neuronal circuits within the basal ganglia, thus confirming the
      role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in
      this disorder.

PMID- 15965210
TI  - Initial DWI and ADC imaging may predict outcome in acute disseminated
      encephalomyelitis: report of two cases of brain stem encephalitis.
AB  - Two young patients with acute disseminated encephalomyelitis (ADEM) of the brain
      stem are described. In spite of similar lesion sites in the brain stem, reaching
      from the upper medulla to the mesencephalon, the outcomes of the patients were
      very different: one made a full clinical recovery within three weeks while the
      other remained in a locked-in state more than a year after the disease episode.
      Both patients also differed in magnetic resonance imaging (MRI) findings on
      admission. The patient who remained in a locked-in state had pathological
      diffusion weighted imaging (DWI) scans and decreased apparent diffusion
      coefficient maps initially, with severe tissue destruction on follow up computed
      tomography, while the patient who recovered fully showed initially increased
      apparent diffusion coefficient values and almost complete resolution of MRI
      changes on follow up. Thus a comparison of these two cases may indicate
      differences in the underlying pathology in ADEM (vasogenic v cytotoxic oedema)
      that may be crucial for estimating tissue damage and clinical outcome.

PMID- 15965211
TI  - Treatment of stiff person syndrome with rituximab.
AB  - This case report is about the novel use of the anti-CD20 antibody, rituximab, in
      the treatment of a 41 year old woman with stiff person syndrome. She was admitted
      to hospital as an emergency with prolonged and painful extensor spasms affecting
      the neck and back, arms, and legs. The disease had progressed despite a
      favourable initial response to conventional treatment with intravenous
      immunoglobulin and cytotoxics. Treatment with rituximab induced a lasting
      clinical remission.

PMID- 15965212
TI  - Utility of an ultrafast magnetic resonance imaging protocol in recent and semi
      recent strokes.
AB  - OBJECTIVE: To evaluate the technical feasibility of an integrated ultrafast head
      magnetic resonance (MR) protocol using a sensitivity encoding (SENSE) technique
      for depicting parenchymal ischaemia and vascular compromise in patients with
      suspected recent stroke. METHODS: 23 patients were evaluated with the ultrafast
      MR protocol using T2, T1, fluid attenuated inversion recovery (FLAIR), 3D time of
      flight magnetic resonance angiography (MRA), and diffusion weighted imaging (DWI)
      sequences. These were compared with routine conventional MR sequences. RESULTS:
      One patient could not tolerate conventional imaging, although imaging using the
      three minute head SENSE protocol was diagnostic. Both conventional and ultrafast
      protocols were of similar diagnostic yield in the remaining patients. There were
      no significant differences in clinical diagnostic quality for the T1, T2, FLAIR,
      and DWI sequences. One MRA examination was of better quality when SENSE was used,
      owing to reduced motion artefacts and shorter imaging time. CONCLUSIONS: It is
      possible to undertake a comprehensive MR examination in stroke patients in
      approximately three to five minutes. Ultrafast imaging may become a useful triage
      tool before thrombolytic therapy. It may be of particular benefit in patients
      unable to tolerate longer sequences. Further work is necessary to confirm these
      findings in hyperacute stroke.

PMID- 15965213
TI  - Family support for stroke: one year follow up of a randomised controlled trial.
AB  - BACKGROUND: There is evidence that family support can benefit carers of stroke
      patients, but not the patients themselves. OBJECTIVE: To extend the follow up of
      a single blind randomised controlled trial of family support for stroke patients
      and carers to one year to ascertain whether there were any late effects of the
      intervention. METHODS: The study was a randomised controlled trial. Patients
      admitted to hospital with acute stroke who had a close carer were assigned to
      receive family support or normal care. Families were visited at home by a
      researcher 12 months after the stroke, and a series of questionnaires was
      administered to patient and carer. RESULTS: The benefits to carers mostly
      persisted, though they were no longer statistically significant because some
      patients were lost to follow up. There was no evidence of any effects on
      patients. CONCLUSION: Family support is effective for carers, but different
      approaches need to be considered to alleviate the psychosocial problems of stroke
      patients.

PMID- 15965214
TI  - Restless legs syndrome and low brain iron levels in patients with
      haemochromatosis.
AB  - Regional brain iron levels of two patients with haemochromatosis and severe
      restless legs syndrome (RLS) were assessed using R2' magnetic resonance imaging
      (MRI) sequences in both patients and in nine healthy controls. R2' relaxation
      rates in the patients were decreased in the substantia nigra, red nucleus, and
      pallidum when compared with the controls. These results indicate that local brain
      iron deficiency may occur in patients with haemochromatosis and suggest a role
      for brain iron metabolism in the pathophysiology of RLS.

PMID- 15965215
TI  - Cerebellar abnormalities on proton MR spectroscopy in gluten ataxia.
AB  - Gluten sensitivity can manifest with ataxia. The metabolic status of the
      cerebellum was investigated in 15 patients with gluten ataxia and 10 controls
      using proton MR spectroscopy. Significant differences were present in mean N
      acetyl aspartate levels at short echo time and N-acetyl aspartate/choline ratios
      at long echo time between the patient and control groups. These data support the
      hypothesis that cerebellar neuronal physiology differs between patients with
      gluten ataxia and healthy controls.

PMID- 15965216
TI  - Fatal toxic leukoencephalopathy: clinical, radiological, and necropsy findings in
      two patients.
AB  - BACKGROUND: Toxic leukoencephalopathy has been described with inhalation and
      intravenous consumption of heroin and cocaine. The clinical picture varies widely
      but the imaging and histological features are characteristic. Magnetic resonance
      imaging (MRI) typically reveals diffuse bihemispheric white matter lesions.
      Histologically there is extensive spongiform degeneration of the cerebral white
      matter. OBJECTIVE: To report two cases of fatal toxin associated
      leukoencephalopathy, along with detailed imaging and neuropathological studies.
      RESULTS: MRI revealed diffuse white matter changes. Histologically there was
      widespread confluent vacuolar degeneration of the deep white matter. In both
      cases, there was sparing of the brain stem and cerebellar white matter. There was
      evidence of severe and extensive axonal injury. CONCLUSIONS: This pattern of
      radiological involvement and histological findings has not previously been
      reported and may reflect the presence of a yet unidentified impurity.

PMID- 15965217
TI  - Bell's palsy with ipsilateral numbness.
AB  - Bell's palsy is an idiopathic facial palsy of the peripheral type. A herpes virus
      is the most likely mechanism. We report a patient with the often encountered
      combination of a facial palsy with ipsilateral sensory changes. Magnetic
      resonance imaging showed had contrast enhancement in the greater petrosal nerve.
      Viral spread through anatomical connections could be an explanation for the
      association of facial palsy with numbness.

PMID- 15965218
TI  - Dominant LMNA mutations can cause combined muscular dystrophy and peripheral
      neuropathy.
AB  - The coexistence of neurogenic and myogenic features in scapuloperoneal syndrome
      is rarely ascribed to a single gene. Defects in the nuclear envelope protein
      lamin A/C, encoded by the LMNA gene, have been shown to be associated with a
      variety of disorders affecting mainly the muscular and adipose tissues and, more
      recently, with autosomal recessive Charcot-Marie-Tooth type 2 neuropathy. This
      report is about a patient presenting features of myopathy and neuropathy due to a
      dominant LMNA mutation, suggesting that the peripheral nerve might be affected in
      primary LMNA myopathy. Our observations further support the marked intrafamilial
      and interfamilial phenotypic heterogeneity associated with lamin A/C defects.

PMID- 15965219
TI  - SPTLC1 and RAB7 mutation analysis in dominantly inherited and idiopathic sensory
      neuropathies.
AB  - BACKGROUND: The variable clinical features of hereditary sensory and autonomic
      neuropathy (HSAN I) suggest heterogeneity. Some cases of idiopathic sensory
      neuropathy could be caused by missense mutations of SPTLC1 and RAB7 and not be
      recognised as familial. OBJECTIVE: To screen persons with dominantly inherited
      HSAN I and others with idiopathic sensory neuropathies for known mutations of
      SPTLC1 and RAB7. PATIENTS: DNA was examined from well characterised individuals
      of 25 kindreds with adult onset HSAN I for mutations of SPTLC1 and RAB7; 92
      patients with idiopathic sensory neuropathy were also screened for known
      mutations of these genes. RESULTS: Of the 25 kindreds, only one had a mutation
      (SPTLC1 399T-->G). This kindred, and 10 without identified mutations, had
      prominent mutilating foot injuries with peroneal weakness. Of the remainder, 12
      had foot insensitivity with injuries but no weakness, one had restless legs and
      burning feet, and one had dementia with hearing loss. No mutation of RAB7 was
      found in any of these. No known mutations of SPTLC1 or RAB7 were found in cases
      of idiopathic sensory neuropathy. CONCLUSIONS: Adult onset HSAN I is clinically
      and genetically heterogeneous and further work is required to identify additional
      genetic causes. Known SPTLC1or RAB7 mutations were not found in idiopathic
      sensory neuropathy.

PMID- 15965220
TI  - Real time polymerase chain reaction: a new powerful tool for the diagnosis of
      neurobrucellosis.
AB  - BACKGROUND/METHODS: We compared the diagnostic yield of a real time polymerase
      chain reaction (PCR) assay in cerebrospinal fluid (CSF) samples with conventional
      microbiological techniques for the diagnosis of neurobrucellosis. Following
      amplification of a 223 bp sequence specific for Brucella genus, melting curve
      analysis was performed to verify the specificity of the PCR products. RESULTS:
      All six patients with neurobrucellosis (three meningitis and three
      meningoencephalitis) had a positive real time PCR assay, whereas CSF cultures and
      Wright seroagglutination tests were positive in only two and four cases,
      respectively. Brucella specific amplicons were easily demonstrated by their
      characteristic melting temperature in all the real time PCR assays. CONCLUSION:
      LightCycler based real time PCR assay in CSF samples is more rapid and sensitive
      than conventional microbiological tests. This technique could be useful for the
      rapid diagnosis of neurobrucellosis.

PMID- 15965221
TI  - Gluten sensitivity and neuromyelitis optica: two case reports.
AB  - Neuromyelitis optica is a clinical syndrome characterised by acute transverse
      myelitis plus an acute or subacute optic neuritis with or without recovery.
      Although once believed to be a variant of multiple sclerosis, diagnostic criteria
      have recently been proposed for neuromyelitis optica, making it a clinically
      distinct syndrome. The term gluten sensitivity refers to a state of heightened
      immunological responsiveness to ingested gluten in genetically susceptible
      individuals, as indicated by circulating antibodies to gliadin. Several
      neurological complications have been described associated with gluten sensitivity
      ranging from peripheral neuropathy and cerebellar ataxia to an increased risk of
      epilepsy. Although myelopathy has been described in some case reports of coeliac
      disease, neuromyelitis optica has never been described in association with gluten
      sensitivity. We describe two cases of gluten sensitivity presenting as
      neuromyelitis optica with no previous history of significant gastrointestinal
      symptoms. Gluten sensitivity was confirmed by immunological and histological
      studies.

PMID- 15965222
TI  - Bilateral subdural haematomata and lumbar pseudomeningocele due to a chronic
      leakage of liquor cerebrospinalis after a lumbar discectomy with the application
      of ADCON-L gel.
AB  - The anti-adhesion gel ADCON-L has been available since the end of the 1990s.
      During disc surgery it can be applied to the spinal nerve roots and the dura
      mater spinalis in order to inhibit fibroblast migration and thus avoid
      postoperative adhesions or excessive keloids, respectively. Due to the way ADCON
      L works, inadvertent, intraoperational dural lesions may stay open much longer
      than usual because ADCON-L inhibits the natural healing process. Possible
      consequences are a chronic leakage of cerebrospinal fluid in combination with
      intracranial hypotension syndrome. We report on a patient who underwent lumbar
      disc surgery with application of ADCON-L gel. Postoperatively he suffered from
      acute headache, nausea, and vomiting. A lumbar pseudomeningocele was demonstrated
      on magnetic resonance imaging (MRI). Furthermore, cranial MRI revealed bilateral,
      chronic subdural haematomata which indicated intracranial hypotension syndrome or
      continuous leakage of cerebrospinal fluid at the lumbar site. With conservative
      treatment the problems were gradually reduced and eventually the subdural
      haematomata were no longer detected. The pseudomeningocele persisted over a 4
      month period of observation. Because of the complications we found, the local
      application of ADCON-L during lumbar disc surgery should be critically evaluated.

PMID- 15965223
TI  - Orthostatic intolerance and syncope associated with Chiari type I malformation.
AB  - The Chiari type I malformation (CM1) is characterized by herniation of cerebellar
      tonsils to at least 3-5 mm below the plane of foramen magnum and can present with
      a wide variety of clinical symptoms, frequently including occipital headaches,
      secondary to bulbar and/or medullary distress. Rarely, syncopal episodes have
      also been described and attributed to either compression of the midbrain
      ascending reticular system, or vascular compromise (vertebrobasilar artery
      compression, hypotension). We report the first case of a CM1 patient with
      frequently recurring syncope due to postural orthostatic tachycardia syndrome
      (POTS), a form of orthostatic intolerance, whose symptoms resolved completely
      after surgical intervention. It is important to stress that it is not clear
      whether the described association of POTS and CM1 in our patient is a fortuitous
      finding in an isolated case or a reflection of a more systematic association
      between the two pathologies.

PMID- 15965224
TI  - Pneumorrhachis of the entire spinal canal.

PMID- 15965225
TI  - Psychiatric side effects during methysergide treatment.
AB  - A patient is reported with psychological change characterised by impaired
      concentration and thought projection, followed by both severe anxiety and
      depression, starting after three weeks on high dose methysergide. The acute
      problem settled slowly after methysergide withdrawal and is likely to represent
      an unusual and serious side effect of that drug.

PMID- 15965226
TI  - An Iranian family with congenital myasthenic syndrome caused by a novel
      acetylcholine receptor mutation (CHRNE K171X).

PMID- 15965227
TI  - Long term results of unilateral posteroventral pallidotomy for antipsychotic drug
      induced tardive dyskinesia.

PMID- 15965228
TI  - Tympanic measurement of body temperature in stroke patients "turned on its ear".

PMID- 15965229
TI  - Transient ischaemic attack with trigeminal autonomic symptoms.

PMID- 15965230
TI  - Protein phosphatase 2A regulates estrogen receptor alpha (ER) expression through
      modulation of ER mRNA stability.
AB  - Protein phosphatase 2A (PP2A) is a ubiquitously expressed member of the serine
      threonine phosphatase family that is involved in regulation of many cellular
      processes including transcription, translation, cellular metabolism, and
      apoptosis. Because of a correlation between PP2A and estrogen receptor alpha (ER)
      expression in several human breast cancer cell lines, the effect of PP2A on
      regulation of ER expression in the human breast cancer cell line MCF-7 was
      studied. Inhibition of PP2A using the pharmacologic inhibitor okadaic acid at 250
      nm for 16 h resulted in a 60% reduction in PP2A activity in MCF-7 cells
      concurrent with a 75% reduction in ER mRNA and protein expression. Similar
      results were obtained with a small interfering RNA probe that specifically
      inhibited PP2A expression. ER promoter studies showed that regulation of ER
      through the PP2A pathway did not occur through transcriptional activation.
      Rather, PP2A mediated ER expression through modulation of ER mRNA stability
      through degradation of ER mRNA, reversible with concomitant treatment with the
      proteasomal inhibitor MG 132. These data suggest a novel pathway controlling ER
      expression resulting from the activation of PP2A, potentially providing a novel
      therapeutic target.

PMID- 15965231
TI  - DNA adduct bypass polymerization by Sulfolobus solfataricus DNA polymerase Dpo4:
      analysis and crystal structures of multiple base pair substitution and frameshift
      products with the adduct 1,N2-ethenoguanine.
AB  - 1,N(2)-Etheno(epsilon)guanine is a mutagenic DNA lesion derived from lipid
      oxidation products and also from some chemical carcinogens. Gel electrophoretic
      analysis of the products of primer extension by Sulfolobus solfataricus P2 DNA
      polymerase IV (Dpo4) indicated preferential incorporation of A opposite 3'
      (1,N(2)-epsilon-G)TACT-5', among the four dNTPs tested individually. With the
      template 3'-(1,N(2)-epsilon-G)CACT-5', both G and A were incorporated. When
      primer extension was done in the presence of a mixture of all four dNTPs, high
      pressure liquid chromatography-mass spectrometry analysis of the products
      indicated that (opposite 3'-(1,N(2)-epsilon-G)CACT-5') the major product was 5'
      GTGA-3' and the minor product was 5'-AGTGA-3'. With the template 3'-(1,N(2)
      epsilon-G)TACT-5', the following four products were identified by high pressure
      liquid chromatography-mass spectrometry: 5'-AATGA-3', 5'-ATTGA-3', 5'-ATGA-3',
      and 5'-TGA-3'. An x-ray crystal structure of Dpo4 was solved (2.1 A) with a
      primer-template and A placed in the primer to be opposite the 1,N(2)-epsilon-G in
      the template 3'-(1,N(2)-epsilon-G)TACT 5'. The added A in the primer was paired
      across the template T with classic Watson-Crick geometry. Similar structures were
      observed in a ternary Dpo4-DNA-dATP complex and a ternary Dpo4-DNA-ddATP complex,
      with d(d)ATP opposite the template T. A similar structure was observed with a
      ddGTP adjacent to the primer and opposite the C next to 1,N(2)-epsilon-G in 3'
      (1,N(2)-epsilon-G)CACT-5'. We concluded that Dpo4 uses several mechanisms,
      including A incorporation opposite 1,N(2)-epsilon-G and also a variation of dNTP
      stabilized misalignment, to generate both base pair and frameshift mutations.

PMID- 15965232
TI  - p300 regulates p63 transcriptional activity.
AB  - The transcriptional co-activator p300 has been reported to regulate the tumor
      suppressor p53 and its ortholog p73. Here we describe a study showing that this
      coactivator also regulates the transcriptional function of p63. p300 bound to the
      N-terminal domain of p63gamma, and p63gamma bound to the N terminus of p300 in
      vitro and in cells. p300, but not its acetylase-defective mutant AT2, stimulated
      p63gamma-dependent transcription and induction of p21 in cells, consequently
      leading to G1 arrest. Inversely, the deltaN-p63gamma isoform as well as p300AT2
      inhibited the induction of p21 by p63gamma. These results suggest that p300
      regulates p63-dependent transcription of p21.

PMID- 15965233
TI  - Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK
      molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9
      phosphorylated at threonine 186.
AB  - Positive transcription elongation factor b (P-TEFb) regulates eukaryotic gene
      expression at the level of elongation, and is itself controlled by the reversible
      association of 7SK RNA and an RNA-binding protein, HEXIM1 or HEXIM2. To further
      understand how P-TEFb is regulated, we analyzed the stoichiometry of all the
      known components of the large, inactive P-TEFb complex. Mutational analyses of a
      putative coiled coil region in the carboxyl-terminal portion of HEXIM1 revealed
      that the protein is a dimer in solution and remains a dimer after binding to 7SK.
      Although a HEXIM1 dimer contains two potential RNA binding motifs and ultimately
      recruits two P-TEFb molecules, it associates with only one molecule of RNA. The
      first 172 nucleotides of the 330-nucleotide 7SK are sufficient to bind HEXIM1 or
      HEXIM2, and then recruit and inhibit P-TEFb. Deletion of the first 121 amino
      acids of HEXIM1 allowed it to inhibit P-TEFb partially in the absence of 7SK RNA.
      Mutation of a conserved tyrosine (Tyr(271) in HEXIM1) to alanine or glutamate or
      mutation of a conserved phenylalanine (Phe(208)) to alanine, aspartate, or
      lysine, resulted in loss of inhibition of P-TEFb, but did not affect formation of
      the 7SK.HEXIM.P-TEFb complex. Analysis of T-loop phosphorylation in Cdk9
      indicated that phosphorylation of Thr(186), but not Ser(175), was essential for
      kinase activity and for recruitment of P-TEFb to the 7SK.HEXIM complex. A model
      illustrates what is currently known about how HEXIM proteins, 7SK, and P-TEFb
      assemble to maintain an activated kinase in a readily available, but inactive
      form.

PMID- 15965234
TI  - The crystal structure of the plexin-semaphorin-integrin domain/hybrid domain/I
      EGF1 segment from the human integrin beta2 subunit at 1.8-A resolution.
AB  - Integrins are modular (alphabeta) heterodimeric proteins that mediate cell
      adhesion and convey signals across the plasma membrane. Interdomain motions play
      a key role in signal transduction by propagating structural changes through the
      molecule, thus controlling the activation state and adhesive properties of the
      integrin. We expressed a soluble fragment of the human integrin beta2 subunit
      comprising the plexin-semaphorin-integrin domain (PSI)/hybrid domain/I-EGF1
      fragment and present its crystal structure at 1.8-A resolution. The structure
      reveals an elongated molecule with a rigid architecture stabilized by nine
      disulfide bridges. The PSI domain is located centrally and participates in the
      formation of extended interfaces with the hybrid domain and I-EGF1 domains,
      respectively. The hybrid domain/PSI interface involves the burial of an Arg
      residue, and contacts between PSI and I-EGF1 are mainly mediated by well
      conserved Arg and Trp residues. Conservation of key interacting residues across
      the various integrin beta subunits sequences suggests that our structure
      represents a good model for the entire integrin family. Superposition with the
      integrin beta3 receptor in its bent conformation suggests that an articulation
      point is present at the linkage between its I-EGF1 and I-EGF2 modules and
      underlines the importance of this region for the control of integrin-mediated
      cell adhesion.

PMID- 15965235
TI  - A novel pathophysiological mechanism for osteoporosis suggested by an in vivo
      gene expression study of circulating monocytes.
AB  - Bone mineral density (BMD) is a major risk factor for osteoporosis. Circulating
      monocytes may serve as early progenitors of osteoclasts and produce a wide
      variety of factors important to bone metabolism. However, little is known about
      the roles of circulating monocytes in relation to the pathophysiology of
      osteoporosis. Using the Affymetrix HG-U133A GeneChip(R) array, we performed a
      comparative gene expression study of circulating monocytes in subjects with high
      and low BMD. We identified in total 66 differentially expressed genes including
      some novel as well as some already known to be relevant to bone metabolism. Three
      genes potentially contributing to bone metabolism, CCR3 (chemokine receptor 3),
      HDC (histidine decarboxylase, i.e. the histamine synthesis enzyme), and GCR
      (glucocorticoid receptor), were confirmed by quantitative real-time reverse
      transcriptase-PCR as up-regulated in subjects with lower BMD. In addition,
      significant negative correlation was observed between expression levels of the
      genes and BMD Z-scores. These three genes and/or their products mediate monocyte
      chemotaxis, histamine production, and/or sensitivity to glucocorticoids. Our
      results suggest a novel pathophysiological mechanism for osteoporosis that is
      characterized by increased recruitment of circulating monocyte into bone,
      enhanced monocyte differentiation into osteoclasts, as well as osteoclast
      stimulation via monocyte functional changes. This is the first in vivo microarray
      study of osteoporosis in humans. The results may contribute to identification of
      new genes and their functions for osteoporosis and suggest genetic markers to
      discern individuals at higher risk to osteoporosis with an aim for preventive
      intervention and treatment.

PMID- 15965236
TI  - Fas binding to calmodulin regulates apoptosis in osteoclasts.
AB  - Promotion of osteoclast apoptosis is one therapeutic approach to osteoporosis.
      Calmodulin, the major intracellular Ca(2+) receptor, modulates both
      osteoclastogenesis and bone resorption. The calmodulin antagonist,
      trifluoperazine, rescues bone loss in ovariectomized mice (Zhang, L., Feng, X.,
      and McDonald, J. M. (2003) Endocrinology 144, 4536-4543). We show here that a 3-h
      treatment of mouse osteoclasts with either of the calmodulin antagonists,
      tamoxifen or trifluoperazine, induces osteoclast apoptosis dose-dependently.
      Tamoxifen, 10 microm, and trifluoperazine, 10 microm, induce 7.3 +/- 1.8-fold and
      5.3 +/- 0.9-fold increases in osteoclast apoptosis, respectively. In Jurkat
      cells, calmodulin binds to Fas, the death receptor, and this binding is regulated
      during Fas-mediated apoptosis (Ahn, E. Y., Lim, S. T., Cook, W. J., and McDonald,
      J. M. (2004) J. Biol. Chem. 279, 5661-5666). In osteoclasts, calmodulin also
      binds Fas. When osteoclasts are treated with 10 microm trifluoperazine, the
      binding between Fas and calmodulin is dramatically decreased at 15 min and
      gradually recovers by 60 min. A point mutation of the Fas death domain in the
      Lpr(-cg) mouse renders Fas inactive. Using glutathione S-transferase fusion
      proteins, the human Fas cytoplasmic domain is shown to bind calmodulin, whereas a
      point mutation (V254N) comparable with the Lpr(-cg) mutation in mice has markedly
      reduced calmodulin binding. Osteoclasts derived from Lpr(-cg) mice have
      diminished calmodulin/Fas binding and are more sensitive to calmodulin antagonist
      induced apoptosis than those from wild-type mice. Both tamoxifen- and
      trifluoperazine-induced apoptosis are increased 1.6 +/- 0.2-fold in Lpr(-cg)
      derived osteoclasts compared with osteoclasts derived from wild-type mice. In
      summary, calmodulin antagonists induce apoptosis in osteoclasts by a mechanism
      involving interference with calmodulin binding to Fas. The effects of
      calmodulin/Fas binding on calmodulin antagonist-induced apoptosis may open a new
      avenue for therapy for osteoporosis.

PMID- 15965237
TI  - Physical and functional mapping of the replication protein a interaction domain
      of the werner and bloom syndrome helicases.
AB  - The single-stranded DNA-binding protein replication protein A (RPA) interacts
      with several human RecQ DNA helicases that have important roles in maintaining
      genomic stability; however, the mechanism for RPA stimulation of DNA unwinding is
      not well understood. To map regions of Werner syndrome helicase (WRN) that
      interact with RPA, yeast two-hybrid studies, WRN affinity pull-down experiments
      and enzyme-linked immunosorbent assays with purified recombinant WRN protein
      fragments were performed. The results indicated that WRN has two RPA binding
      sites, a high affinity N-terminal site, and a lower affinity C-terminal site.
      Based on results from mapping studies, we sought to determine if the WRN N
      terminal region harboring the high affinity RPA interaction site was important
      for RPA stimulation of WRN helicase activity. To accomplish this, we tested a
      catalytically active WRN helicase domain fragment (WRN(H-R)) that lacked the N
      terminal RPA interaction site for its ability to unwind long DNA duplex
      substrates, which the wild-type enzyme can efficiently unwind only in the
      presence of RPA. WRN(H-R) helicase activity was significantly reduced on RPA
      dependent partial duplex substrates compared with full-length WRN despite the
      presence of RPA. These results clearly demonstrate that, although WRN(H-R) had
      comparable helicase activity to full-length WRN on short duplex substrates, its
      ability to unwind RPA-dependent WRN helicase substrates was significantly
      impaired. Similarly, a Bloom syndrome helicase (BLM) domain fragment, BLM(642
      1290), that lacked its N-terminal RPA interaction site also unwound short DNA
      duplex substrates similar to wild-type BLM, but was severely compromised in its
      ability to unwind long DNA substrates that full-length BLM helicase could unwind
      in the presence of RPA. These results suggest that the physical interaction
      between RPA and WRN or BLM helicases plays an important role in the mechanism for
      RPA stimulation of helicase-catalyzed DNA unwinding.

PMID- 15965238
TI  - Intermediate mutation frequencies favor evolution of multidrug resistance in
      Escherichia coli.
AB  - In studying the interplay between mutation frequencies and antibiotic resistance
      among Escherichia coli natural isolates, we observed that modest modifications of
      mutation frequency may significantly influence the evolution of antibiotic
      resistance. The strains having intermediate mutation frequencies have
      significantly more antibiotic resistances than strains having low and high
      mutation frequencies.

PMID- 15965239
TI  - Estimation of preferential pairing rates in second-generation autotetraploid
      pacific oysters (Crassostrea gigas).
AB  - Although previously disregarded, polyploidy, and in particular autopolyploidy, is
      now believed to have played a prominent role in the evolution of plants and
      animals. We estimated the rate of preferential pairing in second-generation
      autotetraploid Pacific oysters from gametic frequencies. We found significant
      levels of preferential pairing in these recently generated autopolyploids,
      suggesting that genetic variation in standing populations may play a role in
      meiotic mechanisms of polyploids derived from these populations.

PMID- 15965240
TI  - Smg1 nonsense mutations do not abolish nonsense-mediated mRNA decay in Drosophila
      melanogaster.
AB  - Smg1 is a key component of nonsense-mediated decay (NMD) in Caenorhabditis
      elegans and mammals. Here we report that two nonsense alleles of the ortholog of
      Smg1 do not affect NMD in Drosophila melanogaster.

PMID- 15965241
TI  - Interaction between genetic background and the mating-type locus in Cryptococcus
      neoformans virulence potential.
AB  - The study of quantitative traits provides a window on the interactions between
      multiple unlinked genetic loci. The interaction between hosts and pathogenic
      microbes, such as fungi, involves aspects of quantitative genetics for both
      partners in this dynamic equilibrium. One important pathogenic fungus is
      Cryptococcus neoformans, a basidiomycete yeast that can infect the human brain
      and whose mating system has two mating type alleles, a and alpha. The alpha
      mating-type allele has previously been linked to increased virulence potential.
      Here congenic C. neoformans strains were generated in the two well-characterized
      genetic backgrounds B3501alpha and NIH433a to examine the potential influence of
      genes outside of the mating-type locus on the virulence potential of mating type.
      The congenic nature of these new strain pairs was established by karyotyping,
      amplified fragment length polymorphism genotyping, and whole-genome molecular
      allele mapping (congenicity mapping). Virulence studies revealed that virulence
      was equivalent between the B3501 a and alpha congenic strains but the alpha
      strain was more virulent than its a counterpart in the NIH433 genetic background.
      These results demonstrate that genomic regions outside the mating type locus
      contribute to differences in virulence between a and alpha cells. The congenic
      strains described here provide a foundation upon which to elucidate at genetic
      and molecular levels how mating-type and other unlinked loci interact to enable
      microbial pathogenesis.

PMID- 15965242
TI  - qUVR-10, a major quantitative trait locus for ultraviolet-B resistance in rice,
      encodes cyclobutane pyrimidine dimer photolyase.
AB  - Rice qUVR-10, a quantitative trait locus (QTL) for ultraviolet-B (UVB) resistance
      on chromosome 10, was cloned by map-based strategy. It was detected in backcross
      inbred lines (BILs) derived from a cross between the japonica variety Nipponbare
      (UV resistant) and the indica variety Kasalath (UV sensitive). Plants homozygous
      for the Nipponbare allele at the qUVR-10 locus were more resistant to UVB
      compared with the Kasalath allele. High-resolution mapping using 1850 F(2) plants
      enabled us to delimit qUVR-10 to a <27-kb genomic region. We identified a gene
      encoding the cyclobutane pyrimidine dimer (CPD) photolyase in this region.
      Activity of CPD photorepair in Nipponbare was higher than that of Kasalath and
      nearly isogenic with qUVR-10 [NIL(qUVR-10)], suggesting that the CPD photolyase
      of Kasalath was defective. We introduced a genomic fragment containing the CPD
      photolyase gene of Nipponbare to NIL(qUVR-10). Transgenic plants showed the same
      level of resistance as Nipponbare did, indicating that the qUVR-10 encoded the
      CPD photolyase. Comparison of the qUVR-10 sequence in the Nipponbare and Kasalath
      alleles revealed one probable candidate for the functional nucleotide
      polymorphism. It was indicated that single-base substitution in the CPD
      photolyase gene caused the alteration of activity of CPD photorepair and UVB
      resistance. Furthermore, we were able to develop a UV-hyperresistant plant by
      overexpression of the photolyase gene.

PMID- 15965243
TI  - High functional overlap between MluI cell-cycle box binding factor and Swi4/6
      cell-cycle box binding factor in the G1/S transcriptional program in
      Saccharomyces cerevisiae.
AB  - In budding yeast, many genes are induced early in the cell cycle. Induction of
      these genes has been predominantly attributed to two transcription factors, Swi4
      Swi6 (SBF) and Mbp1-Swi6 (MBF). Swi4 and Mbp1 are related DNA-binding proteins
      with dissimilar target sequences. For most G1/S-regulated genes that we tested in
      a cdc20 block-release protocol for cell-cycle synchronization, removal of both
      Swi4 and Mbp1 was necessary and sufficient to essentially eliminate cell-cycle
      regulated expression. Detectable SBF or MBF binding sites (SCBs or MCBs) in the
      promoters or available genome-wide promoter occupancy data do not consistently
      explain this functional overlap. The overlapping ability of these transcription
      factors to regulate many promoters with very similar cell-cycle kinetics may
      provide robustness to the G1/S transcriptional response, but poses a puzzle with
      respect to promoter-transcription factor specificity. In addition, for some
      genes, deletion of Mbp1 or Swi4 enhances transcription, suggesting that these
      factors can also function as transcriptional repressors. Finally, we observe
      residual G1/S transcriptional regulation in the absence of Swi4 and Mbp1.

PMID- 15965244
TI  - Identification of a rat model for usher syndrome type 1B by N-ethyl-N-nitrosourea
      mutagenesis-driven forward genetics.
AB  - The rat is the most extensively studied model organism and is broadly used in
      biomedical research. Current rat disease models are selected from existing
      strains and their number is thereby limited by the degree of naturally occurring
      variation or spontaneous mutations. We have used ENU mutagenesis to increase
      genetic variation in laboratory rats and identified a recessive mutant, named
      tornado, showing aberrant circling behavior, hyperactivity, and stereotypic head
      shaking. More detailed analysis revealed profound deafness due to disorganization
      and degeneration of the organ of Corti that already manifests at the onset of
      hearing. We set up a single nucleotide polymorphism (SNP)-based mapping strategy
      to identify the affected gene, revealing strong linkage to the central region of
      chromosome 1. Candidate gene resequencing identified a point mutation that
      introduces a premature stopcodon in Myo7a. Mutations in human MYO7A result in
      Usher syndrome type 1B, a severe autosomal inherited recessive disease that
      involves deafness and vestibular dysfunction. Here, we present the first
      characterized rat model for this disease. In addition, we demonstrate proof of
      principle for the generation and cloning of human disease models in rat using ENU
      mutagenesis, providing good perspectives for systematic phenotypic screens in the
      rat.

PMID- 15965245
TI  - Conserved functions of yeast genes support the duplication, degeneration and
      complementation model for gene duplication.
AB  - Gene duplication is often cited as a potential mechanism for the evolution of new
      traits, but this hypothesis has not been thoroughly tested experimentally. A
      classical model of gene duplication states that after gene duplication one copy
      of the gene preserves the ancestral function, while the other copy is free to
      evolve a new function. In an alternative duplication, divergence, and
      complementation model, duplicated genes are preserved because each copy of the
      gene loses some, but not all, of its functions through degenerating mutations.
      This results in the degenerating mutations in one gene being complemented by the
      other and vice versa. These two models make very different predictions about the
      function of the preduplication orthologs in closely related species. These
      predictions have been tested here for several duplicated yeast genes that
      appeared to be the leading candidates to fit the classical model. Surprisingly,
      the results show that duplicated genes are maintained because each copy carries
      out a subset of the conserved functions that were already present in the
      preduplication gene. Therefore, the results are not consistent with the classical
      model, but instead fit the duplication, divergence, and complementation model.

PMID- 15965246
TI  - X-linked genes evolve higher codon bias in Drosophila and Caenorhabditis.
AB  - Comparing patterns of molecular evolution between autosomes and sex chromosomes
      (such as X and W chromosomes) can provide insight into the forces underlying
      genome evolution. Here we investigate patterns of codon bias evolution on the X
      chromosome and autosomes in Drosophila and Caenorhabditis. We demonstrate that X
      linked genes have significantly higher codon bias compared to autosomal genes in
      both Drosophila and Caenorhabditis. Furthermore, genes that become X-linked
      evolve higher codon bias gradually, over tens of millions of years. We provide
      several lines of evidence that this elevation in codon bias is due exclusively to
      their chromosomal location and not to any other property of X-linked genes. We
      present two possible explanations for these observations. One possibility is that
      natural selection is more efficient on the X chromosome due to effective haploidy
      of the X chromosomes in males and persistently low effective numbers of
      reproducing males compared to that of females. Alternatively, X-linked genes
      might experience stronger natural selection for higher codon bias as a result of
      maladaptive reduction of their dosage engendered by the loss of the Y-linked
      homologs.

PMID- 15965247
TI  - Molecular genetic analysis of the nested Drosophila melanogaster lamin C gene.
AB  - Lamins are intermediate filaments that line the inner surface of the nuclear
      envelope, providing structural support and making contacts with chromatin. There
      are two types of lamins, A- and B-types, which differ in structure and
      expression. Drosophila possesses both lamin types, encoded by the LamC (A-type)
      and lamin Dm0 (B-type) genes. LamC is nested within an intron of the essential
      gene ttv. We demonstrate that null mutations in LamC are lethal, and expression
      of a wild-type LamC transgene rescues lethality of LamC but not ttv mutants.
      Mutations in the human A-type lamin gene lead to diseases called laminopathies.
      To determine if Drosophila might serve as a useful model to study lamin biology
      and disease mechanisms, we generated transgenic flies expressing mutant LamC
      proteins modeled after human disease-causing lamins. These transgenic animals
      display a nuclear lamin aggregation phenotype remarkably similar to that observed
      when human mutant A-type lamins are expressed in mammalian cells. LamC aggregates
      also cause disorganization of lamin Dm0, indicating interdependence of both lamin
      types for proper lamina assembly. Taken together, these data provide the first
      detailed genetic analysis of the LamC gene and support using Drosophila as a
      model to study the role of lamins in disease.

PMID- 15965248
TI  - Haplotype diversity in 11 candidate genes across four populations.
AB  - Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is
      becoming common for both candidate gene and fine-mapping studies. Before
      embarking on studies of haplotypes from genetically distinct populations,
      however, it is important to consider variation both in linkage disequilibrium
      (LD) and in haplotype frequencies within and across populations, as both vary.
      Such diversity will influence the choice of "tagging" SNPs for candidate gene or
      whole-genome association studies because some markers will not be polymorphic in
      all samples and some haplotypes will be poorly represented or completely absent.
      Here we analyze 11 genes, originally chosen as candidate genes for oral clefts,
      where multiple markers were genotyped on individuals from four populations.
      Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity
      were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay
      Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared
      across these four populations and haplotype frequencies were used to assess
      genetic variation. Although these populations are fairly similar in allele
      frequencies and overall patterns of LD, both haplotype frequencies and genetic
      diversity varied significantly across populations. Such haplotype diversity has
      implications for designing studies of association involving samples from
      genetically distinct populations.

PMID- 15965250
TI  - A novel Markov chain monte carlo approach for constructing accurate meiotic maps.
AB  - Mapping markers from linkage data continues to be a task performed in many
      genetic epidemiological studies. Data collected in a study may be used to refine
      published map estimates and a study may use markers that do not appear in any
      published map. Furthermore, inaccuracies in meiotic maps can seriously bias
      linkage findings. To make best use of the available marker information,
      multilocus linkage analyses are performed. However, two computational issues
      greatly limit the number of markers currently mapped jointly; the number of
      candidate marker orders increases exponentially with marker number and computing
      exact multilocus likelihoods on general pedigrees is computationally demanding.
      In this article, a new Markov chain Monte Carlo (MCMC) approach that solves both
      these computational problems is presented. The MCMC approach allows many markers
      to be mapped jointly, using data observed on general pedigrees with unobserved
      individuals. The performance of the new mapping procedure is demonstrated through
      the analysis of simulated and real data. The MCMC procedure performs extremely
      well, even when there are millions of candidate orders, and gives results
      superior to those of CRI-MAP.

PMID- 15965249
TI  - Genetic instability induced by overexpression of DNA ligase I in budding yeast.
AB  - Recombination and microsatellite mutation in humans contribute to disorders
      including cancer and trinucleotide repeat (TNR) disease. TNR expansions in wild
      type yeast may arise by flap ligation during lagging-strand replication. Here we
      show that overexpression of DNA ligase I (CDC9) increases the rates of TNR
      expansion, of TNR contraction, and of mitotic recombination. Surprisingly, this
      effect is observed with catalytically inactive forms of Cdc9p protein, but only
      if they possess a functional PCNA-binding site. Furthermore, in vitro analysis
      indicates that the interaction of PCNA with Cdc9p and Rad27p (Fen1) is mutually
      exclusive. Together our genetic and biochemical analysis suggests that, although
      DNA ligase I seals DNA nicks during replication, repair, and recombination,
      higher than normal levels can yield genetic instability by disrupting the normal
      interplay of PCNA with other proteins such as Fen1.

PMID- 15965251
TI  - RESISTANCE TO FUSARIUM OXYSPORUM 1, a dominant Arabidopsis disease-resistance
      gene, is not race specific.
AB  - Arabidopsis thaliana ecotypes differ in their susceptibility to Fusarium wilt
      diseases. Ecotype Taynuilt-0 (Ty-0) is susceptible to Fusarium oxysporum forma
      specialis (f.) matthioli whereas Columbia-0 (Col-0) is resistant. Segregation
      analysis of a cross between Ty-0 and Col-0 revealed six dominant RESISTANCE TO
      FUSARIUM OXYSPORUM (RFO) loci that significantly contribute to f. matthioli
      resistance in Col-0 relative to Ty-0. We refer to the locus with the strongest
      effect as RFO1. Ty-0 plants in which only the Col-0 allele of RFO1 (RFO1(Col-0))
      was introduced were resistant to f. matthioli. Surprisingly, RFO1(Col-0) also
      conferred resistance to f. raphani, demonstrating that RFO1-mediated resistance
      is not race specific. Expression of resistance by RFO2, RFO4, or RFO6 was
      dependent on RFO1(Col-0). Map-based cloning of RFO1(Col-0) showed that RFO1 is
      identical to the previously named Arabidopsis gene WAKL22 (WALL-ASSOCIATED KINASE
      LIKE KINASE 22), which encodes a receptor-like kinase that does not contain an
      extracellular leucine-rich repeat domain. Consistent with these results, a Col-0
      rfo1 loss-of-function mutant was more susceptible to f. matthioli, f.
      conglutinans, and f. raphani. Thus, RFO1 encodes a novel type of dominant disease
      resistance protein that confers resistance to a broad spectrum of Fusarium races.

PMID- 15965252
TI  - Positive assortative mating with family size as a function of predicted parental
      breeding values.
AB  - While other investigations have described benefits of positive assortative mating
      (PAM) for forest tree breeding, the allocation of resources among mates in these
      studies was either equal or varied, using schemes corresponding only to parental
      rank (i.e., more resources invested in higher-ranking parents). In this
      simulation study, family sizes were proportional to predicted midparent BLUP
      values. The distribution of midparent BLUP values was standardized by a constant,
      which was varied to study the range of distributions of family size.
      Redistributing progenies from lower- to higher-ranking families to a point where
      an equal number of progenies were still selected out of each family to the next
      generation caused minimal change in group coancestry and inbreeding in the
      breeding population (BP), while the additive genetic response and variance in the
      BP were both greatly enhanced. This generated additional genetic gains for forest
      plantations by selecting more superior genotypes from the BP (compared to PAM
      with equal family sizes) for production of improved regeneration materials. These
      conclusions were verified for a range of heritability under a polygenic model and
      under a mixed-inheritance model with a QTL contributing to the trait variation.

PMID- 15965253
TI  - The Drosophila meiotic mutant mei-352 is an allele of klp3A and reveals a role
      for a kinesin-like protein in crossover distribution.
AB  - The semisterile meiotic mutant mei-352 alters the distribution of meiotic
      exchanges without greatly affecting their total frequency. We show that the mei
      352 mutation is an allele of the klp3A gene, which encodes a kinesin-like protein
      of the Kinesin-4 family. The semisterility observed in mei-352 females results
      from a known defect of klp3A oocytes in mediating pronuclear fusion.
      Interestingly, other klp3A alleles also exhibit defects in meiotic recombination
      similar to those of mei-352. Finally, we show that the Klp3A protein localizes
      within the oocyte nucleus during meiotic prophase, the time at which exchange
      distribution is established, and extensively colocalizes with DNA. The parallel
      of the klp3A phenotype with a meiotic defect observed for kar3 mutants in yeast
      suggests a role for kinesins in early meiosis and might reflect a previously
      suggested role for this class of kinesins in chromosome condensation.

PMID- 15965254
TI  - Modeling linkage disequilibrium in natural populations: the example of the Soay
      sheep population of St. Kilda, Scotland.
AB  - The use of linkage disequilibrium to localize the genes underlying quantitative
      traits has received considerable attention in the livestock genetics community
      over the past few years. This has resulted in the investigation of linkage
      disequilibrium structures of several domestic livestock populations to assess
      their potential use in fine-mapping efforts. However, the linkage disequilibrium
      structure of free-living populations has been less well investigated. As the
      direct evaluation of linkage disequilibrium can be both time consuming and
      expensive the use of simulations that include as many aspects of population
      history as possible is advocated as an alternative. A simulation of the linkage
      disequilibrium structure of the Soay sheep population of St. Kilda, Scotland, is
      provided as an example. The simulated population showed significant decline of
      linkage disequilibrium with genetic distance and low levels of background linkage
      disequilibrium, indicating that the Soay sheep population is a viable resource
      for linkage disequilibrium fine mapping of quantitative trait loci.

PMID- 15965255
TI  - Concerted evolution in the repeats of an immunomodulating cell surface protein,
      SOWgp, of the human pathogenic fungi Coccidioides immitis and C. posadasii.
AB  - Genome dynamics that allow pathogens to escape host immune responses are
      fundamental to our understanding of host-pathogen interactions. Here we present
      the first population-based study of the process of concerted evolution in the
      repetitive domain of a protein-coding gene. This gene, SOWgp, encodes the
      immunodominant protein in the parasitic phase of the human pathogenic fungi
      Coccidioides immitis and C. posadasii. We sequenced the entire gene from strains
      representing the geographic ranges of the two Coccidioides species. By using
      phylogenetic and genetic distance analyses we discovered that the repetitive part
      of SOWgp evolves by concerted evolution, predominantly by the mechanism of
      unequal crossing over. We implemented a mathematical model originally developed
      for multigene families to estimate the rate of homogenization and recombination
      of the repetitive array, and the results indicate that the pattern of concerted
      evolution is a result of homogenization of repeat units proceeding at a rate
      close to the nucleotide point mutation rate. The release of the SOWgp molecules
      by the pathogen during proliferation may mislead the host: we speculate that the
      pathogen benefits from concerted evolution of repeated domains in SOWgp by an
      enhanced ability to misdirect the host's immune system.

PMID- 15965257
TI  - Approximating identity-by-descent matrices using multiple haplotype
      configurations on pedigrees.
AB  - Identity-by-descent (IBD) matrix calculation is an important step in quantitative
      trait loci (QTL) analysis using variance component models. To calculate IBD
      matrices efficiently for large pedigrees with large numbers of loci, an
      approximation method based on the reconstruction of haplotype configurations for
      the pedigrees is proposed. The method uses a subset of haplotype configurations
      with high likelihoods identified by a haplotyping method. The new method is
      compared with a Markov chain Monte Carlo (MCMC) method (Loki) in terms of QTL
      mapping performance on simulated pedigrees. Both methods yield almost identical
      results for the estimation of QTL positions and variance parameters, while the
      new method is much more computationally efficient than the MCMC approach for
      large pedigrees and large numbers of loci. The proposed method is also compared
      with an exact method (Merlin) in small simulated pedigrees, where both methods
      produce nearly identical estimates of position-specific kinship coefficients. The
      new method can be used for fine mapping with joint linkage disequilibrium and
      linkage analysis, which improves the power and accuracy of QTL mapping.

PMID- 15965256
TI  - Gene arrays at Pneumocystis carinii telomeres.
AB  - In the fungus Pneumocystis carinii, at least three gene families (PRT1, MSR, and
      MSG) have the potential to generate high-frequency antigenic variation, which is
      likely to be a strategy by which this parasitic fungus is able to prolong its
      survival in the rat lung. Members of these gene families are clustered at
      chromosome termini, a location that fosters recombination, which has been
      implicated in selective expression of MSG genes. To gain insight into the
      architecture, evolution, and regulation of these gene clusters, six telomeric
      segments of the genome were sequenced. Each of the segments began with one or
      more unique genes, after which were members of different gene families, arranged
      in a head-to-tail array. The three-gene repeat PRT1-MSR-MSG was common,
      suggesting that duplications of these repeats have contributed to expansion of
      all three families. However, members of a gene family in an array were no more
      similar to one another than to members in other arrays, indicating rapid
      divergence after duplication. The intergenic spacers were more conserved than the
      genes and contained sequence motifs also present in subtelomeres, which in other
      species have been implicated in gene expression and recombination. Long
      mononucleotide tracts were present in some MSR genes. These unstable sequences
      can be expected to suffer frequent frameshift mutations, providing P. carinii
      with another mechanism to generate antigen variation.

PMID- 15965258
TI  - Functional mapping of quantitative trait loci that interact with the hg mutation
      to regulate growth trajectories in mice.
AB  - The high growth (hg) mutation increases body size in mice by 30-50%. Given the
      complexity of the genetic regulation of animal growth, it is likely that the
      effect of this major locus is mediated by other quantitative trait loci (QTL)
      with smaller effects within a web of gene interactions. In this article, we
      extend our functional mapping model to characterize modifier QTL that interact
      with the hg locus during ontogenetic growth. Our model is derived within the
      maximum-likelihood context, incorporated by mathematical aspects of growth laws
      and implemented with the EM algorithm. In an F2 population founded by a congenic
      high growth (HG) line and non-HG line, a highly additive effect due to the hg
      gene was detected on growth trajectories. Three QTL located on chromosomes 2 and
      X were identified to trigger significant additive and/or dominant effects on the
      process of growth. The most significant finding made from our model is that these
      QTL interact with the hg locus to affect the shapes of the growth process. Our
      model provides a powerful means for understanding the genetic architecture and
      regulation of growth rate and body size in mammals.

PMID- 15965259
TI  - Genetic consequences of selection during the evolution of cultivated sunflower.
AB  - We mapped quantitative trait loci (QTL) controlling differences in seed oil
      content and composition between cultivated and wild sunflower and used the
      results, along with those of a previous study of domestication-related QTL, to
      guide a genome-wide analysis of genetic variation for evidence of past selection.
      The effects of the seed oil QTL were almost exclusively in the expected direction
      with respect to the parental phenotypes. A major, oil-related QTL cluster mapped
      near a cluster of domestication-related QTL on linkage group six (LG06), the
      majority of which have previously been shown to have effects that are
      inconsistent with the parental phenotypes. To test the hypothesis that this
      region was the target of a past selective sweep, perhaps resulting in the
      fixation of the antagonistic domestication-related QTL, we analyzed simple
      sequence repeat (SSR) diversity from 102 markers dispersed throughout the
      sunflower genome. Our results indicate that LG06 was most likely the target of
      multiple selective sweeps during the postdomestication era. Strong directional
      selection in concert with genetic hitchhiking therefore offers a possible
      explanation for the occurrence of numerous domestication-related QTL with
      apparently maladaptive phenotypic effects.

PMID- 15965260
TI  - Kin selection is implicated in partial sib-mating populations with constant
      viability differences before mating.
AB  - The change in the frequency of a rare mutant allele under constant sex
      differentiated viability selection in an infinite, partial full-sib mating
      population is studied. The diplo-diploid and haplo-diploid polygynous models are
      considered with a Poisson distribution for the number of offspring produced by
      every mated female. Reproduction is followed by weak selection among the
      offspring and then mating to form the next generation. It is shown that the rate
      of change with respect to the frequency of the mutant allele and the intensity of
      selection can be expressed in terms of costs or benefits of substituting the
      mutant type for the wild type, which correspond to average excesses in viability
      in females and males, multiplied by coefficients of relatedness to the
      individuals affected by such a substitution and reproductive values associated to
      the sexes of these individuals. This reveals hidden interactions between mated
      individuals and between males for mating, the former having positive effects on
      the reproductive success of related individuals and the latter having negative
      effects. Such interactions are the result of reproductive constraints when a
      fixed proportion of females must mate with a male sib and all females are
      fertilized as long as one mate is available. However, they affect the change in
      allele frequency because there is inbreeding or relatedness between mates and
      more generally relatedness between interacting individuals. Surprisingly, the
      effects of these interactions cancel out in a diploid population when the number
      of offspring is large enough so that the possibility for a female to have no male
      sib to mate with can be neglected and the viability differences are the same in
      both sexes.

PMID- 15965262
TI  - Combining the meiosis Gibbs sampler with the random walk approach for linkage and
      association studies with a general complex pedigree and multimarker loci.
AB  - A linkage analysis for finding inheritance states and haplotype configurations is
      an essential process for linkage and association mapping. The linkage analysis is
      routinely based upon observed pedigree information and marker genotypes for
      individuals in the pedigree. It is not feasible for exact methods to use all such
      information for a large complex pedigree especially when there are many missing
      genotypic data. Proposed Markov chain Monte Carlo approaches such as a single
      site Gibbs sampler or the meiosis Gibbs sampler are able to handle a complex
      pedigree with sparse genotypic data; however, they often have reducibility
      problems, causing biased estimates. We present a combined method, applying the
      random walk approach to the reducible sites in the meiosis sampler. Therefore,
      one can efficiently obtain reliable estimates such as identity-by-descent
      coefficients between individuals based on inheritance states or haplotype
      configurations, and a wider range of data can be used for mapping of quantitative
      trait loci within a reasonable time.

PMID- 15965261
TI  - A Drosophila model of multiple endocrine neoplasia type 2.
AB  - Dominant mutations in the Ret receptor tyrosine kinase lead to the familial
      cancer syndrome multiple endocrine neoplasia type 2 (MEN2). Mammalian tissue
      culture studies suggest that RetMEN2 mutations significantly alter Ret-signaling
      properties, but the precise mechanisms by which RetMEN2 promotes tumorigenesis
      remain poorly understood. To determine the signal transduction pathways required
      for RetMEN2 activity, we analyzed analogous mutations in the Drosophila Ret
      ortholog dRet. Overexpressed dRetMEN2 isoforms targeted to the developing retina
      led to aberrant cell proliferation, inappropriate cell fate specification, and
      excessive Ras pathway activation. Genetic analysis indicated that dRetMEN2 acts
      through the Ras-ERK, Src, and Jun kinase pathways. A genetic screen for mutations
      that dominantly suppress or enhance dRetMEN2 phenotypes identified new genes that
      are required for the phenotypic outcomes of dRetMEN2 activity. Finally, we
      identified human orthologs for many of these genes and examined their status in
      human tumors. Two of these loci showed loss of heterozygosity (LOH) within both
      sporadic and MEN2-associated pheochromocytomas, suggesting that they may
      contribute to Ret-dependent oncogenesis.

PMID- 15965263
TI  - A segmental deletion series generated by sister-chromatid transposition of Ac
      transposable elements in maize.
AB  - Certain configurations of maize Ac/Ds transposon termini can undergo alternative
      transposition reactions leading to chromosome breakage and various types of
      stable chromosome rearrangements. Here, we show that a particular allele of the
      maize p1 gene containing an intact Ac element and a nearby terminally deleted Ac
      element (fAc) can undergo sister-chromatid transposition (SCT) reactions that
      generate large flanking deletions. Among 35 deletions characterized, all begin at
      the Ac termini in the p1 gene and extend to various flanking sites proximal to
      p1. The deletions range in size from the smallest of 12,567 bp to the largest of
      >4.6 cM; >80% of the deletions removed the p2 gene, a paralog of p1 located
      approximately 60 kb from p1 in the p1-vv allele and its derivatives. Sequencing
      of representative cases shows that the deletions have precise junctions between
      the transposon termini and the flanking genomic sequences. These results show
      that SCT events can efficiently generate interstitial deletions that are useful
      for in vivo dissection of local genome regions and for the rapid correlation of
      genetic and physical maps. Finally, we discuss evidence suggesting that deletions
      induced by alternative transposition reactions can occur at other genomic loci,
      indicating that this mechanism may have had a significant impact on genome
      evolution.

PMID- 15965265
TI  - Mystery of the missing denture: an unusual cause of respiratory arrest in a
      nonagenarian.
AB  - To ask older people about loose or ill-fitting dentures is not common practice
      during a hospital admission. Our patient presented to the emergency department
      following a primary respiratory arrest. A dislodged denture was extracted from
      the hypo-pharynx under local anaesthesia and was presumably the cause of the
      respiratory arrest. Any delays in finding the missing denture and its extraction
      could have resulted in the patient being given a general anaesthetic and its
      associated complications. We suggest that asking about loose-fitting dentures
      should form part of comprehensive geriatric assessment.

PMID- 15965264
TI  - Multilocus analysis of introgression between two sympatric sister species of
      Drosophila: Drosophila yakuba and D. santomea.
AB  - Drosophila yakuba is widely distributed in sub-Saharan Africa, while D. santomea
      is endemic to the volcanic island of Sao Tome in the Atlantic Ocean, 280 km west
      of Gabon. On Sao Tome, D. yakuba is found mainly in open lowland forests, and D.
      santomea is restricted to the wet misty forests at higher elevations. At
      intermediate elevations, the species form a hybrid zone where hybrids occur at a
      frequency of approximately 1%. To determine the extent of gene flow between these
      species we studied polymorphism and divergence patterns in 29 regions distributed
      throughout the genome, including mtDNA and three genes on the Y chromosome. This
      multilocus approach, together with the comparison to the two allopatric species
      D. mauritiana and D. sechellia, allowed us to distinguish between forces that
      should affect all genes and forces that should act on some genes (e.g.,
      introgression). Our results show that D. yakuba mtDNA has replaced that of D.
      santomea and that there is also significant introgression for two nuclear genes,
      yellow and salr. The majority of genes, however, has remained distinct. These two
      species therefore do not form a "hybrid swarm" in which much of the genome shows
      substantial introgression while disruptive selection maintains distinctness for
      only a few traits (e.g., pigmentation and male genitalia).

PMID- 15965266
TI  - Accelerated discovery of novel protein function in cultured human cells.
AB  - Experimental approaches that enable direct investigation of human protein
      function are necessary for comprehensive annotation of the human proteome. We
      introduce a cell-based platform for rapid and unbiased functional annotation of
      undercharacterized human proteins. Utilizing a library of antibody biomarkers,
      the full-length proteins are investigated by tracking phenotypic changes caused
      by overexpression in human cell lines. We combine reverse transfection and
      immunodetection by fluorescence microscopy to facilitate this procedure at high
      resolution. Demonstrating the advantage of this approach, new annotations are
      provided for two novel proteins: 1) a membrane-bound O-acyltransferase protein
      (C3F) that, when overexpressed, disrupts Golgi and endosome integrity due likely
      to an endoplasmic reticulum-Golgi transport block and 2) a tumor marker (BC-2)
      that prompts a redistribution of a transcriptional silencing protein (BMI1) and a
      mitogen-activated protein kinase mediator (Rac1) to distinct nuclear regions that
      undergo chromatin compaction. Our strategy is an immediate application for
      directly addressing those proteins whose molecular function remains unknown.

PMID- 15965267
TI  - The subunit structure and dynamics of the 20S proteasome in chicken skeletal
      muscle.
AB  - We have succeeded in purifying the 20S core proteasome particle from less than 1
      g of skeletal muscle in a rapid process involving two chromatographic steps. The
      individual subunits were readily resolved by two-dimensional PAGE, and the
      identities of each of the 14 subunits were assigned by a combination of peptide
      mass fingerprinting and MS/MS/de novo sequencing. To assess the dynamics of
      proteasome biogenesis, chicks were fed a diet containing stable isotope-labeled
      valine, and the rate of incorporation of label into valine-containing peptides
      derived from each subunit was assessed by mass spectrometric analysis after two
      dimensional separation. Peptides containing multiple valine residues from the 20S
      proteasome and other soluble muscle proteins were analyzed to yield the relative
      isotope abundance of the precursor pool, a piece of information that is essential
      for calculation of turnover parameters. The rates of synthesis of each subunit
      are rather similar, although there is evidence for high turnover subunits in both
      the alpha (nonproteolytic) and beta (proteolytic) rings. The variability in
      synthesis rate for the different subunits is consistent with a model in which
      some subunits are produced in excess, whereas others may be the rate-limiting
      factor in the concentration of 20S subunits in the cell. The ability to measure
      turnover rates of proteins on a proteome-wide scale in protein assemblies and in
      a complex organism provides a new dimension to the understanding of the dynamic
      proteome.

PMID- 15965268
TI  - Developmental anatomy of the root cortex of the basal monocotyledon, Acorus
      calamus (Acorales, Acoraceae).
AB  - BACKGROUND AND AIMS: The anatomical structure and development of adventitious
      roots were analysed in the basal monocotyledon, Acorus calamus, to determine to
      what extent those features are related to phylogenetic position. METHODS: Root
      specimens were harvested and sectioned, either with a hand microtome or freehand,
      at varying distances from the root tip and examined under the microscope using a
      variety of staining techniques. KEY RESULTS: Roots of Acorus calamus possess a
      unique set of developmental characteristics that produce some traits similar to
      those of another basal angiosperm group, Nymphaeales. The root apical meristem
      organization seems to be intermediate between that of a closed and an open
      monocotyledonous root apical meristem organization. The open-type root apical
      meristem consists of a curved zone of cortical initials and epidermal initials
      overlying the vascular cylinder initials; the epidermal part of the meristem
      varies in its association with the cortical initials and columellar initials of
      the promeristem. The cortex develops an endodermis with only Casparian bands, a
      dimorphic exodermis with Casparian bands and suberin lamellae, and a polygonal
      aerenchyma by differential expansion, as also observed in the Nymphaeales and
      some dicotyledonous species. The stele has characteristics like those of members
      of the Nymphaeaceae. CONCLUSIONS: Specific anatomical and developmental
      attributes of Acorus roots seem to be related to the phylogenetic position of
      this genus.

PMID- 15965269
TI  - Selective transport of zinc, manganese, nickel, cobalt and cadmium in the root
      system and transfer to the leaves in young wheat plants.
AB  - BACKGROUND AND AIMS: The uptake, translocation and redistribution of the heavy
      metals zinc, manganese, nickel, cobalt and cadmium are relevant for plant
      nutrition as well as for the quality of harvested plant products. The long
      distance transport of these heavy metals within the root system and the release
      to the shoot in young wheat (Triticum aestivum 'Arina') plants were investigated.
      METHODS: After the application of 65Zn, 54Mn, 63Ni, 57Co and 109Cd for 24 h to
      one seminal root (the other seminal roots being excised) of 54-h-old wheat
      seedlings, the labelled plants were incubated for several days in hydroponic
      culture on a medium without radionuclides. KEY RESULTS: The content of 65Zn
      decreased quickly in the labelled part of the root. After the transfer of 65Zn
      from the roots to the shoot, a further redistribution in the phloem from older to
      younger leaves was observed. In contrast to 65Zn, 109Cd was released more slowly
      from the roots to the leaves and was subsequently redistributed in the phloem to
      the youngest leaves only at trace levels. The content of 63Ni decreased quickly
      in the labelled part of the root, moving to the newly formed parts of the root
      system and also accumulating transiently in the expanding leaves. The 54Mn
      content decreased quickly in the labelled part of the root and increased
      simultaneously in leaf 1. A strong retention in the labelled part of the root was
      observed after supplying 57Co. CONCLUSIONS: The dynamics of redistribution of
      65Zn, 54Mn, 63Ni, 57Co and 109Cd differed considerably. The rapid redistribution
      of 63Ni from older to younger leaves throughout the experiment indicated a high
      mobility in the phloem, while 54Mn was mobile only in the xylem and 57Co was
      retained in the labelled root without being loaded into the xylem.

PMID- 15965270
TI  - Leaf evolution: gases, genes and geochemistry.
AB  - AIMS: This Botanical Briefing reviews how the integration of palaeontology,
      geochemistry and developmental biology is providing a new mechanistic framework
      for interpreting the 40- to 50-million-year gap between the origination of
      vascular land plants and the advent of large (megaphyll) leaves, a long-standing
      puzzle in evolutionary biology. SCOPE: Molecular genetics indicates that the
      developmental mechanisms required for leaf production in vascular plants were
      recruited long before the advent of large megaphylls. According to theory, this
      morphogenetic potential was only realized as the concentration of atmospheric CO2
      declined during the late Palaeozoic. Surprisingly, plants effectively policed
      their own evolution since the decrease in CO2 was brought about as terrestrial
      floras evolved accelerating the rate of silicate rock weathering and enhancing
      sedimentary organic carbon burial, both of which are long-term sinks for CO2.
      CONCLUSIONS: The recognition that plant evolution responds to and influences
      CO(2) over millions of years reveals the existence of an intricate web of
      vegetation feedbacks regulating the long-term carbon cycle. Several of these
      feedbacks destabilized CO2 and climate during the late Palaeozoic but appear to
      have quickened the pace of terrestrial plant and animal evolution at that time.

PMID- 15965271
TI  - Key plant structural and allocation traits depend on relative age in the
      perennial herb Pimpinella saxifraga.
AB  - BACKGROUND AND AIMS: Perennial plant formations always include a mixture of
      various-aged individuals of community-creating species, but the physiological and
      competitive potentials of plants of differing age and the importance on whole
      community functioning are still not entirely known. The current study tested the
      hypothesis that ontogenetically old plants have limited biomass investments in
      leaves and enhanced foliage support costs. METHODS: Leaf structure, size and
      biomass allocation were studied in the perennial herb Pimpinella saxifraga during
      plant ontogeny from seedling to senile phases to determine age-dependent controls
      on key plant structural traits. The average duration of the full ontogenetic
      cycle is approx. 5-10 years in this species. Plants were sampled from shaded and
      open habitats. KEY RESULTS: Leaflet dry mass per unit area (M(A)) increased, and
      the fraction of plant biomass in leaflets (F(L)) decreased with increasing age,
      leading to a 5- to 11-fold decrease in leaf area ratio (LAR = F(L)/M(A)) between
      seedlings and senescent plants. In contrast, the fraction of below-ground biomass
      increased with increasing age. Leaflet size and number per leaf increased with
      increasing age. This was not associated with enhanced support cost in older
      plants as age-dependent changes in leaf shape and increased foliage packing along
      the rachis compensated for an overall increase in leaf size. Age-dependent trends
      were the same in habitats with various irradiance, but the LAR of plants of
      varying age was approx. 1.5-fold larger in the shade due to lower M(A) and larger
      F(L). CONCLUSIONS: As plant light interception per unit total plant mass scales
      with LAR, these data demonstrate major age-dependent differences in plant light
      harvesting efficiency that are further modified by site light availability. These
      ontogenetic changes reduce the differences among co-existing species in perennial
      communities, and therefore need consideration in our understanding of how
      herbaceous communities function.

PMID- 15965273
TI  - Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma
      pathogenesis.
AB  - The aim of this study was to discuss the relevance of the Epstein-Barr virus
      (EBV) in the nasopharyngeal carcinoma (NPC), analyzing the variations of several
      molecules potentially involved in the pathogenesis of this cancer. EBV was
      detected in all the NPC samples by several techniques including PCR, in situ
      hybridization, and immunohistochemical methodologies. CD21 membrane receptor was
      absent after EBV infection, being a differential morphological feature of the
      tumoral cells. Latent membrane protein-1 (LMP1), an oncogenic viral product, was
      detected in a high percentage of samples, supporting a role for EBV in the
      pathogenesis of NPC. Bcl-2, an anti-apoptotic protein up-regulated by LMP1, was
      also overexpressed, coinciding with the majority of samples positive for LMP1.
      Finally, p53 presented abnormalities only in a low percentage of samples. These
      results reinforce the role of the EBV in the NPC discussing several potential
      mechanisms of pathogenesis in this neoplasia.

PMID- 15965272
TI  - Metastatic melanoma: is biochemotherapy the future?
AB  - Current treatment options in metastatic melanoma are of limited efficacy.
      Achievement of durable responses with biological agents, and the possibility to
      complement the higher response rate of chemotherapy and combined chemotherapy by
      prolonged duration of responses, led to development of biochemotherapy. Although
      a clear improvement in response rate (40-60% OR) resulted in some studies of the
      combined modality, several phase III studies had mixed results on the duration of
      survival. Various timeframes between the administration of chemotherapy and
      biologics have been tested, ranging between concurrent biochemotherapy, 1 d
      (immediately sequential), and up to 3 wk (long sequence or alternating). An
      analysis of the trend of responses and survival versus the duration of the
      chemobiotherapy sequence showed that, as the timeframe between chemo and bio
      components increases, the overall survival, survival of complete responders, and
      survival of partial responders appear to increase, but the effect is only present
      for the chemo-bio, and not for the bio-chemo sequence. Because there is no
      current explanation for this observation, it appears possible that the
      interaction between components of biochemotherapy results in a double effect: an
      increase in the immediate response reflected in the OR, CR, PR on one side, and
      an increase in survival on the other side. An analysis of mechanisms involved in
      the response leads us hypothesize that macrophage activation, as measured by the
      neopterin levels, may correlate with the survival of patients undergoing
      biochemotherapy, while the generation of nitric oxide, acting synergistically
      with chemotherapy in producing tumor cell killing, may be reflected in the
      overall response rate seen with the biochemotherapy combinations.

PMID- 15965274
TI  - Changes of cerebrospinal fluid tumor marker levels may predict response to
      treatment and survival of carcinomatous meningitis in patients with advanced
      breast cancer.
AB  - The aim of the present study was to evaluate the predictive value of
      cerebrospinal fluid (CSF) tumor marker levels in patients with breast cancer and
      carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA
      125, and CA-19.9) measurements were performed in five patients with breast cancer
      developing carcinomatous meningitis in an attempt to correlate these with
      clinical outcome under treatment. CSF tumor marker levels correlated with
      response to treatment and outcome in each patient, and, despite achieving
      negative CSF cytology after therapy in two patients, it heralded disease
      progression. Given our findings, CSF tumor marker evaluation may provide a
      reliable means and surrogate end-points of monitoring response of carcinomatous
      meningitis to treatment. Therefore, large studies to assess the value of CSF
      tumor marker changes in carcinomatous meningitis are warranted.

PMID- 15965275
TI  - In vitro and in vivo antitumorigenic activity of a mixture of lysine, proline,
      ascorbic acid, and green tea extract on human breast cancer lines MDA-MB-231 and
      MCF-7.
AB  - Current treatments are generally ineffective once breast cancer has metastasized;
      median survival is reduced to 2-3 yr. Previous research studies demonstrating
      potent synergistic antitumor activity of lysine, proline, ascorbic acid, and
      epigallocatechin gallate prompted us to investigate the in vivo inhibitory effect
      of a nutrient mixture containing lysine, proline, arginine, ascorbic acid, and
      epigallocatechin gallate (NM) on the growth of human cancer xenografts in female
      athymic nude mice. Five to six week old female mice were inoculated with 3x106
      breast cancer cells MDA-MB-231. After injection, the mice were randomly divided
      into two groups A and B; group A was fed a regular diet and group B with the
      regular diet supplemented with 0.5% of the nutrient mixture (NM). Four weeks
      later, the mice were sacrificed, and their tumors were excised, weighed, and
      processed for histology. We also tested the effect of NM in vitro on estrogen
      receptor positive (ER+) MCF-7 and estrogen-receptor negative (ER-) MDA-MB-231
      breast cancer cell lines by measuring: cell proliferation by MTT assay,
      expression of MMPs by gelatinase zymography, invasion through Matrigel, and VEGF
      by ELISA. MCF-7 cells were also treated with estradiol to study enhanced invasion
      and expression of MMPs and VEGF. Results showed that NM inhibited the growth and
      reduced the size of tumors in female nude mice by 27%. Furthermore, histological
      evaluation revealed increased mitotic index, MMP-9 and VEGF secretion, and PAS
      material (mucin) in the control group tissues. In vitro studies showed NM
      inhibited MDA-MB-231 cell growth by 34% at 500 microg/mL and MCF-7 cell growth by
      18% at 1000 microg/mL. Invasion of MDA-MB-231 through Matrigel was inhibited by
      50%, 60%, and 95% by 10, 50, and 100 microg/mL of NM, respectively. The results
      of this study demonstrated that the nutrient mixture tested significantly
      suppressed tumor growth of breast cancer cells in female athymic nude mice and
      significantly inhibited MMP expression, angiogenesis, and invasion in breast
      cancer cells, in vitro, offering promise for therapeutic use in the treatment of
      breast cancer.

PMID- 15965277
TI  - A phase II study of weekly paclitaxel and carboplatin in previously untreated
      patients with advanced non-small-cell lung cancer.
AB  - PURPOSE: Both paclitaxel (P) and carboplatin (C) have a significant activity in
      non-small cell lung cancer (NSCLC). Weekly administration of P is active, is dose
      intense, and has a favorable toxicity profile. To evaluate the efficacy and
      toxicity of weekly P and C in advanced-stage NSCLC, we initiated this phase II
      study in patients with advanced NSCLC (III B with pleural effusion and stage IV).
      PATIENTS AND METHODS: Eligible patients were treated with paclitaxel 100 mg/m2
      intravenously (iv) over 1 h followed by carboplatin AUC 2 iv over 30 min. This
      treatment was administered weekly for 3 of every 4 wk until disease progression
      or intolerable toxicities. RESULTS: Of the 30 patients enrolled in the study, one
      patient did not meet the eligibility criteria. Of the remaining 29 patients, 6
      did not complete at least two cycles of treatment and hence were not assessable
      for response. The overall response rate was 43.5% (10/23) (all partial
      responses). An additional 43.5% had stable disease. The median time to
      progression was 162 d and the median duration of response was 169 d. Overall
      survival at 1 yr on intent-to-treat analyses was 44% and median survival was 10.8
      mo. We observed the following grade 3/4 toxicities: hypersensitivity to
      paclitaxel (13%), hypersensitivity to carboplatin (3%), neutropenia (31%),
      thrombocytopenia (7%); 31% experienced grade 1 neuropathy and 17% experienced
      grade 2 neuropathy. CONCLUSIONS: We conclude that weekly paclitaxel and
      carboplatin is active and very well tolerated in patients with advanced NSCLC.

PMID- 15965276
TI  - The value of serum Bcl-2 levels in advanced lung cancer patients.
AB  - Overexpression of the Bcl-2 protein was associated with a favorable prognostic
      factor for survival in lung cancer patients, especially nonsmall cell lung
      carcinoma. The present study was conducted to investigate the value of serum Bcl
      2 levels in advanced lung cancer patients. Fifty patients with advanced lung
      carcinoma pathologically verified and 18 healthy controls were investigated.
      Serum samples were obtained on the first admission before the chemotherapeutic
      treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2
      monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly
      higher in patients with lung cancer than in the control group (p<0.001). Serum
      Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the
      prognostic parameters analyzed, such as age of patient, gender, histology, stage
      of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE,
      LDH, performance of patient, weight loss, and response to chemotherapy, was
      significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2
      concentrations were not changed with cisplatin-based cytotoxic chemotherapy
      regardless of response (p=0.76). No prognostic value of serum Bcl-2 was
      determined. In conclusion, the results of the present study, which is the first
      study to determine serum Bcl-2 levels in lung cancer, suggest that decreased
      apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer
      patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung
      cancer patients. However, more studies are needed to define the role of Bcl-2 in
      the diagnosis and prognosis of lung cancer.

PMID- 15965278
TI  - Irinotecan plus cisplatin combination against metastatic gastric cancer: phase II
      study.
AB  - In this phase II study, we aimed to detect efficacy and toxicity of the
      combination of CPT-11 and cisplatin administered to patients with metastatic
      gastric carcinoma. On d 1, CPT-11, 100 mg/m2, was administered by intravenous
      infusion for 90 min, followed by a 2 h infusion of cisplatin, at 70 mg/m2 every 3
      wk. Forty-one patients were enrolled into the study. Twenty-eight patients were
      chemotherapy naive. The total number of chemotherapy cycles administered was 165,
      and the median number of cycles received was 4 (range, 1-8 cycles). The median
      follow-up time was 12 mo (range, 4-34 mo). There were 4 complete responses (9.7%)
      and 14 partial responses (34.2%), which result in a response rate of 43.9% (18 of
      41 patients). The median time to progression was 8.0 +/- 0.8 mo with 56% and 13%
      of patients progression free at 6 and 12 mo, respectively. The median overall
      survival was 9.0 +/- 1.1 mo, with 68 % and 32% of patients alive at 6 and 12 mo,
      respectively. Grade 3-4 nausea and vomiting was observed in five patients (12%)
      and grade 3-4 neutropenia in five patients (12%). Grade 3 infection was observed
      in only one patient (2%). Grade 2 transient liver dysfunction related to
      chemotherapy was observed in one patient (2%). Chemotherapy was stopped due to
      nephrotoxicity in one patient (2%). There was no treatment-related death. In
      conclusion, administration of CPT-11 and cisplatin in this particular dose every
      3 wk is effective and well-tolerated treatment regimen.

PMID- 15965280
TI  - Hypocellular myelodysplastic syndromes: clinical and biological significance.
AB  - The article is concerned with incidence, clinical features, response to therapy,
      and prognosis of patients with hypocellular myelodysplastic syndromes. Bone
      marrow (BM) cellularity <30% (or <20% in patients >70 yr) was found in 24 of 236
      (10.2%) trephine biopsies. Median age was 61 yr, with significant male
      predominance (M/F=3.0) At diagnosis, median hemoglobin was 83 g/L, median
      platelet and neutrofil counts were 31x109/L and 1.2x109/L, respectively.
      According to FAB classification, 17 patients had RA, 6 had RAEB, and only 1 had
      RAEB-t. Beside marrow hypoplasia, the most prominent PH finding was megakaryocyte
      hypoplasia and dysplasia, found in two-thirds of cases, each. Comparison between
      hypocellular and normo/hypercellular MDS cases regarding clinicopathological
      features showed younger age, more severe cytopenia, less blood and BM blast
      infiltration, MK hypoproliferation, and more pronounced stromal reactions in
      former cases. Karyotypic abnormalities were present in 12.5% hypocellular cases,
      in contrast to 44.6% normo/hypercellular cases (p=0.0025). Eleven patients were
      treated with supportive therapy alone, six with danazol or androgens, six with
      immunosuppressive therapy, and one with LDARAC. However, complete or partial
      response was achieved in only four patients treated with danazol or androgens.
      None of the patients developed leukemia. Eleven patients died, so marrow
      insufficiency was the main cause of death. Median survival was 33 mo for
      hypocellular MDS, and 19 mo for normo/hypercellular MDS (p=0.09). The results
      confirm the existence of hypocellular variant of MDS, which seems to have better
      prognosis than those patients with normo/hypercellular disease.

PMID- 15965279
TI  - Anemia in cervical cancer patients: implications for iron supplementation
      therapy.
AB  - Iron deficiency and tumor bleeding are common causes of anemia in cervical
      cancer. Anemia has a negative prognostic influence, and its correction is thought
      to improve prognosis; therefore, most patients are treated with either
      transfusion and/or erythropoietin. At present little is known about the value of
      iron stores replenishment to increase hemoglobin levels in this setting.
      Untreated cervical cancer patients with a hemoglobin <12 g/dL were randomized to
      intramuscular iron or to transfusion. Iron dose was calculated according to
      [weight (kg)x(15--actual Hb)x2.4]+500 and administered by injections of 200 mg
      daily. In both arms, patients who did not achieve at least 10 g/dL hemoglobin
      before or during chemoradiation were transfused. Patients received standard
      pelvic radiation plus six weekly doses of cisplatin. Hematic counts were
      performed before starting chemoradiation and weekly thereafter. Fifteen patients
      were studied; six were assigned to iron and nine to transfusion. Mean basal
      hemoglobin levels were 9.9 and 9.5 g/dL respectively. Total iron, saturation
      index, binding capacity, and ferritin were within normal limits, although there
      was a high variability among the patients. The mean total dose of iron
      administered was 1229 mg. Two weeks after randomization, hemoglobin increased to
      10.9 and 10.2 g/dL respectively. At wk 1 of treatment and thereafter, levels were
      higher in the iron arm, in whom the values were close or higher than 12 g/dL
      (p=0.03). The median number of units transfused were 0 in the iron group and 2 in
      the transfusion (p=0.02) arm. Parenteral iron seems to be effective to increase
      hemoglobin in cervical cancer patients.

PMID- 15965281
TI  - Apoptosis of lymphocytes in peripheral blood of patients with melanoma.
AB  - In cancer, spontaneous apoptosis of circulating peripheral blood lymphocytes
      (PBLs) is a general phenomenon. In this study we aimed to determine whether
      spontaneous apoptosis of circulating PBLs of patients with malignant melanoma
      occurs. Pathologically proven 45 patients with malignant melanoma and 19 healthy
      controls were included in this study. Samples were obtained both on first
      admission before treatment, either adjuvant or metastatic, and follow-up period
      of patients. Human active caspase-3 immunoassay (R&D Systems, Inc. MN, USA)
      employs the quantitative sandwich enzyme immunoassay technique. A monoclonal
      specific for caspase-3 has been used. The spontaneously apoptotic PBLs in
      melanoma patients were not significantly different from those obtained for normal
      controls (p=0.25). None of the clinical characteristics were significantly
      correlated with spontaneous apoptosis (p>0.05). Likewise, we found that apoptosis
      in PBLs was not a prognostic factor in melanoma patients (p=0.79). In conclusion,
      we did not observe accelerated apoptosis of PBLs in patients with melanoma.
      Further studies are necessary to determine the potential prognostic importance of
      this observation.

PMID- 15965282
TI  - Bcl-xl expression in multiple myeloma.
AB  - In the present study the immunohistochemical expression of Bcl-xl, a downstream
      target of the IL-6-controlled signal transducer and activator of transcription-3
      (Stat3) was studied in 40 multiple myeloma (MM) cases before treatment and 11 MM
      patients at relapse. Correlation analysis was performed between Bcl-xl
      expression, C-reactive protein (CRP) level, beta-2-microglobulin (beta2m),
      microvessel density (MVD), and clinical outcome. Before treatment 28 (70%)
      patients demonstrated a Bcl-xl expression similar to normal plasma cells ("normal
      pattern"), while 12 (30%) patients demonstrated an elevated expression in a
      subgroup of the malignant plasma cells. At relapse, no change in Bcl-xl
      expression was observed as compared to pretreatment sample. No correlation was
      observed between the Bcl-xl expression and the level of CRP and b2m. In addition,
      no significant correlation was observed between the Bcl-xl expression and the
      MVD, but MVD was significantly increased as compared to normal bone marrow biopsy
      specimens (p=0.02). Patients with an elevated or normal Bcl-xl expression showed
      no statistically significant difference in overall and event-free survival. In
      summary, these data indicate that Bcl-xl is elevated in a subgroup of MM patients
      that so far did not correlate with CRP, b2m, MVD, and clinical outcome.

PMID- 15965283
TI  - Treatment of a patient with a nodal peripheral T-cell lymphoma
      (angioimmunoblastic T-Cell lymphoma) with a human monoclonal antibody against the
      CD4 antigen (HuMax-CD4).
AB  - A patient with a CD4+ refractory peripheral T-cell lymphoma (PTL), subtype
      angioimmunoblastic T-cell lymphoma (AILD), was treated with a human monoclonal
      anti-CD4 antibody (HuMax-CD4) iv once weekly for 10 wk. Early during treatment
      all palpable enlarged lymph nodes disappeared. A decline of normal CD4+ T-cells
      in the blood mirrored the treatment effect. Shortly after stopping treatment the
      patient relapsed with new enlarged lymph nodes. This time no antitumor effect was
      seen when HuMax-CD4 treatment was reinstituted. No severe side effects were
      observed during the antibody treatment. This case report is the first describing
      that HuMax-CD4 has antilymphoma activity in PTL and is an interesting drug to
      study further in patients with CD4+ PTL.

PMID- 15965284
TI  - Randomized, open label, prospective study on the effect of zoledronic acid on the
      prevention of bone metastases in patients with recurrent solid tumors that did
      not present with bone metastases at baseline.
AB  - OBJECTIVES: Bisphosphonates have been used successfully in the treatment of
      hypercalcemia and to reduce skeletal-related complications of bone metastases.
      Recent in vitro and in vivo evidence suggest that they may also have direct
      antitumor effects via induction of apoptosis, inhibition of the invasive
      potential of tumor cell lines in vitro, inhibition of angiogenesis, and reduction
      in tumor growth indirectly via effects on accessory cells. This is a randomized,
      open label, prospective study that examined the effect of preventive zoledronic
      acid treatment on the development of bone metastases in patients with recurrent
      solid tumors, without bone metastases at the time of randomization. METHODS:
      Forty patients with recurrent or metastatic advanced cancer, without bone
      metastases, were randomized into the trial to either receive zoledronic acid or
      no treatment. Patients were followed up until bone metastases were established.
      RESULTS: The percentage of patients being bone metastases free at 12 mo was 60%
      in the zoledronic acid and 10% in the control group (p<0.0005), while the
      percentages at 18 mo were 20% and 5% respectively (p=0.0002). CONCLUSIONS: The
      results have shown that bisphosphonates as adjuvant treatment might be useful for
      the prevention of bone metastases; however, there is need for blinded randomized
      data before such an approach would be confirmed. In the meantime preventive use
      of bisphosphonates in patients without any bone metastases should not be used
      outside the scope of a clinical trial.

PMID- 15965285
TI  - Acute tumor lysis syndrome triggered by zoledronic Acid in a patient with
      metastatic lung adenocarcinoma.
AB  - We report the case of a 52-yr-old man with metastatic lung adenocarcinoma who
      developed tumor lysis syndrome after administration of zoledronic acid. Tumor
      lysis syndrome in solid tumors and the antitumor effect of the zolendronic acid
      are discussed in light of the pertinent literature.

PMID- 15965286
TI  - Plasmacytoma of the lung: an indolent disease resistant to conventional myeloma
      treatment: report of a case.
AB  - Solitary lung plasmacytoma is a rare form of plasma cell tumors. The case of a 56
      yr-old man is presented, who had a massive tumor of the right pulmonary apex.
      Percutaneous transthoracic lung biopsy demonstrated a tumor-cell population
      consisting of mature plasma cells, proplasmacytes, and rare plasmablasts.
      Immunohistochemically, the cells were CD79a+, kappa+, cyclin D1-, p53-, MDR-.
      Proliferative index was low (number of Ki-67+ tumor cells was 8%). Serum and
      urine immunoelectrophoresis did not show the presence of paraprotein. Screening
      for multiple myeloma with skeletal X-ray survey and bone marrow biopsy were
      negative. Radiotherapy and chemotherapy with alkylating agents were ineffective.
      However, the course of the disease is indolent and the patient is well, alive,
      and with no signs of multiple myeloma >5 yr after the diagnosis was established.
      Some pathogenetic aspects of tumor resistance to conventional myeloma treatment
      in this case are discussed.

PMID- 15965287
TI  - The physician and the other: images of the charlatan in medieval Islam.
AB  - Physicians have always tried to demarcate themselves from the Other, whom they
      labeled as a "charlatan." During the medieval period, Arabic physicians such as
      al-Razi attacked charlatans in their theoretical and deontological writings, and,
      like their Greek predecessors, called on the authorities to stamp out
      malpractice. Their advice was partly heeded, as can be seen from manuals on
      market inspection (hisba). Physicians accused their colleagues of quackery based
      on charges of incompetence or deceit, which must be seen partly as an attempt to
      protect themselves from potential competitors. Certain groups of society,
      including women and Jews, were an especially convenient target. Moreover,
      charlatans also appear in nonmedical texts such as al-Gaubari's manual on
      tricksters and al-Hariri's Assemblies or Maqamat. These accounts suggest that,
      despite the calls of the medical elite to exclude quacks from the marketplace,
      the latter were able to attract customers and continue to practice.

PMID- 15965288
TI  - "Stop this overwhelming torment of destiny": negotiating financial aid at times
      of sickness under the English Old Poor Law, 1800-1840.
AB  - The issue of entitlement under the English Poor Law (1601-1834) is a complex
      question, and nowhere more so than in the context of the sick poor. Using the
      example of communities in one of England's most parsimonious Poor Law counties,
      Lancashire, this article will show that the sick poor faced uncertain and uneven
      entitlement to relief and medical intervention. Faced with such uncertainty, they
      adopted three core linguistic and posturing strategies when attempting to
      establish their eligibility for relief in the eyes of Poor Law officials. Pauper
      letters and the correspondence of overseers of the poor and vestries are used to
      unpick the process of obtaining poor relief and to highlight the subtle
      strategization of pauper applicants. The article concludes by suggesting that
      there may have been a regional patterning in access to medical relief in England
      in the last decades of the Old Poor Law.

PMID- 15965289
TI  - Malarial birds: modeling infectious human disease in animals.
AB  - Through the examination of avian malarias as models of infectious human disease,
      this paper reveals the kinds of claims that scientists and physicians made on the
      basis of animal models-biological systems in the laboratory and the field-and
      what characteristics made for congruence between these models and human malaria.
      The focus is on the period between 1895 and 1945, and on the genesis and
      trajectory of certain animal models of malaria within specific locations, such as
      the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I.
      G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to
      malaria-as-disease, and the difficulties of framing aspects of this disease
      complex within an animal or laboratory system. The diversity and nearness to wild
      types of the birds, protozoan parasites, and mosquitoes that made up these
      malaria models contributed a great deal to the complexity of the models. Avian
      malarias, adopted with enthusiasm, were essential to the success of the U.S.
      antimalarial program during World War II.

PMID- 15965290
TI  - Selskar Gunn and China: The Rockefeller Foundation's "other" approach to public
      health.
AB  - The Rockefeller Foundation's program for rural development in China was developed
      by Selskar Gunn during the period 1932-34 and was initiated in 1935. It was
      multidisciplinary in nature, and its aim was to raise the educational, social,
      and economic standards of rural China. It was recognized by some at the time as
      an alternative to the International Health Division's approach to public health.
      This paper describes the program, what led Gunn to develop it in China, and the
      internal tensions that it created. Also addressed is the question of why this
      program had such limited impact on subsequent developments in the field of
      international health.

PMID- 15965295
TI  - Rapid categorization of pathogenic Escherichia coli by multiplex PCR.
AB  - A one-shot multiplex polymerase chain reaction (PCR) was developed for detecting
      12 virulence genes of diarrheagenic Escherichia coli. In order to differentiate
      between the five categories of diarrheagenic E. coli, we selected the target
      genes: stx1, stx2, and eaeA for enterohemorrhagic E. coli(EHEC); eaeA, bfpA, and
      EAF for enteropathogenic E. coli(EPEC); invE for enteroinvasive E. coli(EIEC);
      elt, estp, and esth for enterotoxigenic E. coli(ETEC); CVD432 and aggR for
      enteroaggregative E. coli(EAggEC); and astA distributed over the categories of
      diarrheagenic E. coli. In our multiplex PCR system, all 12 targeted genes (stx1,
      stx2, eaeA, invE, elt, estp, astA, esth, bfpA, aggR, EAF, and CVD432) were
      amplified in a single PCR reaction in one tube and detected by electrophoresis.
      Using our multiplex PCR, the 208 clinically isolated strains of diarrheagenic E.
      coli in our laboratory were successfully categorized and easily analyzed for the
      presence of virulence plasmids.

PMID- 15965296
TI  - Interleukin-8 secretion by epithelial cells infected with diffusely adherent
      Escherichia coli possessing Afa adhesin-coding genes.
AB  - Escherichia coli that adhere sparsely to human epithelial (HEp-2) cells are known
      as diffusely adherent E. coli(DAEC) and considered potentially diarrheagenic. The
      role of the afimbrial adhesive sheath (Afa)-identified originally as a
      uropathogenic factor-in diffuse adhesion is now understood. However, the role of
      DAEC in diarrheal disease remains controversial. Recently, ability to induce
      interleukin-8 (IL-8) secretion from intestinal epithelial cells has been
      suggested as one of the properties of enterovirulent bacteria. In this study, we
      examined whether DAEC strains possessing Afa genes induced IL-8 in cultures of
      human carcinoma epithelial cells (e.g., HEp-2, Caco-2, and T84). Nineteen afa
      positive DAEC strains were examined for their ability to induce IL-8 secretion,
      and only 7 strains (37%; 7/19) induced IL-8 as much as enteroaggregative E. coli
      did. No marked differences in adhesion were observed between high and low
      inducers. Diffusive adhesiveness itself is unlikely to be sufficient to induce IL
      8. All high inducers were motile and others were nonmotile. Additional
      stimulation by flagella may be required to cause high levels of chemokine
      induction. Motility or presence of flagella can be an important criterion to
      predict DAEC diarrheagenicity at clinical laboratories.

PMID- 15965297
TI  - Application of real-time PCR for quantitative detection of Clostridium botulinum
      type A toxin gene in food.
AB  - The TaqMan real-time PCR method for the quantitative detection of C. botulinum
      type A was developed based on sequence-specific hybridization probes. The
      validity of this assay was verified by using 10 genera of 20 strains, including
      reference strains of C. botulinum types A, B, C, D, E and F. The detection limit
      of this assay was evaluated on C. botulinum type A, using a 10-fold dilution
      series of DNA and spores . The DNA and spores were detected up to level of 0.1
      ng/ml and 10(2)spores/ml, respectively. Spore spiked food sample preparation
      prior to the real-time PCR was performed by two methods, heat treatment and
      GuSCN. The detection limits after heat treatment showed 10(2) spores/ml for
      spiked sausage slurry, and 10(3) spores/ml for spiked canned corn slurry, while
      detection limits after GuSCN precipitation showed 10(2) spores/ml in both sausage
      and canned corn. Therefore the real-time PCR assay after GuSCN precipitation is
      useful for the quantification of C. botulinum type A because it showed identical
      CT values in both pure spore solutions and food slurries. We suggest that
      quantitative analysis of C. botulinum type A by TaqMan real-time PCR can be a
      rapid and accurate assessment method for botulinal risk in food samples.

PMID- 15965298
TI  - The cytotoxin-hemolysin genes of human and eel pathogenic Vibrio vulnificus
      strains: comparison of nucleotide sequences and application to the genetic
      grouping.
AB  - Vibrio vulnificus can be divided into two groups on the basis of pathogenesis.
      Group 1 is pathogenic only to humans, whereas group 2 is pathogenic to eels and
      occasionally to humans. Although both groups produce a 50-kDa cytotoxin-hemolysin
      (V. vulnificus hemolysin; VVH), the toxins are different. In the present study,
      the nucleotide sequence of the toxin gene (vvhA ) of strain CDC B3547 (a group 2
      strain) was determined, and the deduced amino acid sequence was compared to that
      of strain L-180 (a group 1 strain). The nucleotide sequence of vvhA of strain CDC
      B3547 was about 96% identical with that of strain L-180, which results in a
      difference of 3 amino acid residues in the C-terminal lectin domain of VVH.
      Nevertheless, two primer sets for polymerase chain reaction could be designed to
      differentiate the toxin gene of each strain. When 27 V. vulnificus clinical
      isolates were tested, group 1 strains (9 strains) were shown to react only to the
      primers designed for vvhA of strain L-180; whereas, the gene of group 2 strains
      (18 strains) could be amplified with the primers for vvhA of strain CDC B3547.
      These findings may lead to development of a novel genetic grouping system related
      to the virulence potential or to the host range.

PMID- 15965299
TI  - Seroprevalence to the circumsporozoite protein peptide antigen of Plasmodium
      vivax in Korean children.
AB  - Recently, malaria re-emerged in the Republic of Korea (ROK), but there have been
      only a few reports on malaria seroprevalence. For the epidemiological study in
      children, a total of 1,176 serum samples were obtained from children and
      adolescent inhabitants from the three different regions, Pajoo, the Guro district
      in the western part of Seoul (Guro), and Ansan, from June to September 2002, when
      the transmission rate was high. Anti-circumsporozoite protein (CSP) antibody
      levels were assessed in samples using an indirect enzyme-linked immunosorbent
      assay (ELISA) method. Among the three regions, the highest IgG seroreactivity
      against the CSP antigen of Plasmodium vivax was found in the children from Pajoo
      (8.0%), followed by the children from Guro (3.2%), and those in Ansan (0.02%) had
      the lowest seroreactivity. In Pajoo, the profile of antibody response showed the
      highest in age 9, but decreased with age towards 12 years old. We found
      significant correlation between the seroprevalence and annual incidence in the
      investigated areas, suggesting that the area-related patterns reflected the
      differences of inoculation rates in children.

PMID- 15965300
TI  - A quantitative analysis of cedar pollen-specific immunoglobulins in nasal lavage
      supported the local production of specific IgE, not of specific IgG.
AB  - Many studies have proved the relevance of local immune responses, rather than
      systemic immunity, to the pathogenesis of allergic rhinitis. Indeed, allergen
      specific B lymphocyte undergoes class switching to IgE in situ. However, the
      relative contribution of in situ production to the amount in serum is still
      ambiguous. Here, a quantitative comparison of the local concentration of allergen
      specific IgE with the systemic concentration was explored for the estimation.
      Among seasonal rhinitis patients, total and Japanese cedar pollen (JCP)-specific
      IgE, IgA and IgG antibodies were quantified in nasal lavage fluid (NLF) and serum
      with the time-resolved fluorescence immunosorbent assay. Although the total
      amounts of IgE and IgG classes in the NLF, which were apparently passive
      discharge from the mucosal tissue, were smaller and variable, the relative
      proportions of JCP-specific antibodies could be quantitatively compared between
      NLF and serum or between subjects. The proportions of specific IgE in the NLF
      were remarkably higher than in serum (average 13.2-fold) in most subjects, which
      strongly supported the predominant in situ production of the specific IgE and
      subsequent dilutions in the systemic circulations. Similar but smaller values
      were obtained for IgA (average 3.7-fold). In contrast, the specific proportions
      of IgG in the NLF were surprisingly consistent with serum (average 1.0-fold),
      suggesting that the specific IgG was mostly produced in the downstream lymphoid
      organs. The local productions of specific IgE would encourage the topical
      therapies and the usage of the NLF for the diagnosis of allergic rhinitis.

PMID- 15965301
TI  - CCR7 ligand-enhanced phagocytosis of various antigens in mature dendritic cells
      time course and antigen distribution different from phagocytosis in immature
      dendritic cells.
AB  - CC chemokine receptor 7 (CCR7) is selectively expressed on mature dendritic cells
      (DC). The CCR7 ligands, CC chemokine ligand (CCL) 19 and CCL21, facilitate
      migration of mature DC from the peripheral tissues to regional lymph nodes. We
      previously demonstrated that CCR7 ligands induced rapid receptor-mediated
      endocytosis of dextran in mature DC. In the present study, we further examined
      the effects of CCR7 ligands on endocytosis of other kinds of antigen,
      mannosilated bovine serum albumin (Mann-BSA), Escherichia coli(E. coli), or
      ovalbumin-containing immune complex (OVA-IC), by mature DC. We found that CCR7
      ligands enhanced the endocytosis of Mann BSA, E. coli, and OVA-IC in mature DC
      but not in immature DC. The endocytosis of BSA was not enhanced by CCR7 ligands.
      Furthermore, the phagocytosis of OVA-IC was significantly inhibited by anti
      Fcgamma receptor III/II antibody. These results demonstrate that CCR7 ligands
      enhance only receptor-mediated endocytosis by mature DC. When rapidly
      phagocytosed E. coli were traced in CCL19-treated mature DC, most of the
      phagocytosed E. coli did not colocalize with the lysosomal marker: lysosome
      associated membrane protein-1 (Lamp-1), whereas most of E. coli taken up
      relatively slowly by immature DC colocalized with Lamp-1. These results suggest
      that phagocytosis of antigens by immature and mature DC plays different
      functional roles.

PMID- 15965302
TI  - Rapid and simple identification of Orientia tsutsugamushi from other group
      rickettsiae by duplex PCR assay using groEL gene.
AB  - In this study, two new duplex PCR methods based on the groEL gene were developed
      and investigated for the diagnosis of rickettsiae. The first duplex PCR assay
      amplified the 229-bp and the 366-bp DNAs of 6 strains including typhus group (TG)
      and spotted fever group (SFG) rickettsiae, and 5 scrub typhus group (STG)
      rickettsiae, respectively. The second duplex PCR assay amplified the 397-bp and
      the 213-bp DNAs of 6 Rickettsia strains and 5 STG strains. These duplex PCR
      methods could simultaneously perform the rapid identification of rickettsiae and
      the differential diagnosis of STG and other group rickettsiae in a single
      reaction.

PMID- 15965303
TI  - Chemokine and cytokine production in susceptible C3H/HeN mice and resistant
      BALB/c mice during Orientia tsutsugamushi infection.
AB  - To understand the pathogenesis of scrub typhus, we examined chemokine and
      cytokine production in susceptible (C3H/HeN) and resistant (BALB/c) mice after
      infection with O. tsutsugamushi Gilliam. C3H/HeN mice produced high levels of
      chemokines macrophage inflammatory proteins 1 alpha (MIP-1 alpha ), MIP-2,
      monocyte chemoattractant protein 1 (MCP-1), and cytokines gamma-interferon (IFN
      gamma ), interleukin-12 (IL-12), IL-10, and tumor necrosis factor alpha (TNF
      alpha ) in response to O. tsutsugamushi infection, compared to BALB/c mice.
      Chemokine profiles in infected mice correlated well with the kinetics of
      inflammatory cell infiltration. Hyperproduction of chemokines and cytokines was
      observed in another susceptible-infection model (BALB/c-Karp). These results
      suggest that hyperproduction of chemokines and cytokines are associated with
      susceptibility during O. tsutsugamushi infection.

PMID- 15965304
TI  - Practical range of effective dose for Cre recombinase-expressing recombinant
      adenovirus without cell toxicity in mammalian cells.
AB  - The site-specific recombinase Cre is valuable for regulation of gene expression
      not only in vitro but also in vivo. We previously reported that replication
      deficient recombinant adenovirus (rAd) expressing Cre can mediate efficient and
      strict regulation in 100% of cultured cells. Recently, the constitutive
      expression of Cre using retrovirus or lentivirus vector reportedly inhibited cell
      growth, but the effect of transient Cre expression have not yet been examined.
      Here we showed that an excess amount of Cre produced from Cre-expressing rAd
      caused a deleterious effect in cells even when Cre was transiently expressed. We
      used three rAds carrying promoters with different activities: the SV40 early
      promoter (AxSVENCre), the SR alpha promoter (AxSRCre) and the CAG promoter
      (AxCANCre). Cell toxicity was clearly caused by Cre itself and was
      distinguishable from that caused by rAd virions when the cytopathic effects of
      these rAds were compared with that of a control virus lacking the Cre expression
      unit. Cre toxicity was strongly correlated with the expression level of Cre.
      Importantly, AxSRCre and AxCANCre gave a 60-fold range of effective MOIs
      ("effective range") sufficient for gene activation without causing cell toxicity
      from either the rAd particles or Cre itself, while AxSVENCre failed to give such
      a range because the expression level of Cre was too low. When Cre was tagged with
      a nuclear localization signal (NLS), not only its activity but also Cre toxicity
      was increased fourfold, and the effective range was unchanged. Therefore,
      AxSRNCre might be more useful to control cell toxicity from the rAd virions than
      AxSRCre. Cre-induced cell toxicity can be avoided by pre-examining the "effective
      range" using the purpose cell lines before starting experiments utilizing the
      experiment of Cre-expressing rAd.

PMID- 15965305
TI  - Medical jargon: obstacle to effective communication between physicians and
      patients.

PMID- 15965307
TI  - Safety, tolerability, and efficacy of continuous transdermal dopaminergic
      stimulation with rotigotine patch in early-stage idiopathic Parkinson disease.
AB  - Rotigotine is a new dopamine agonist with transdermal patch formulation for the
      treatment of Parkinson disease. The aim of this study was to investigate safety
      and efficacy of rotigotine in patients with early-stage Parkinson disease. In
      this open-label, dose-escalation, safety and efficacy study, 31 patients in the
      early stages of idiopathic Parkinson disease received rotigotine to a maximum of
      18.0 mg/day. Of the 29 patients who completed the 28-day treatment phase, 24 were
      maintained at the maximum dose level. The drug was well tolerated, and skin
      reactions were mild. A statistically significant improvement in UPDRS I, II, and
      III scores was observed from baseline to end of treatment for the 29 subjects who
      completed the trial. Mean improvement (+/- standard deviation) was -0.41 +/- 0.78
      on UPDRS I (P = 0.0078), -2.76 +/- 3.31 on UPDRS II (P = 0.0001), and -4.62 +/-
      5.32 on UPDRS III (P < 0.0001). When results were stratified by maximum dose
      achieved, significant improvements were seen on all 3 subscores for patients
      achieving the maximum dose. These data suggest that rotigotine is a safe, well
      tolerated, and effective treatment for early-stage Parkinson disease.

PMID- 15965308
TI  - Use of ziprasidone in parkinsonian patients with psychosis.
AB  - Twelve patients with Parkinson disease and psychosis were included in an open
      label 12-week trial of ziprasidone. Two patients withdrew from the treatment
      because of adverse effects. The remaining 10 patients reported a significant
      improvement in psychiatric symptoms. Altogether, there was no deterioration of
      motor symptoms (UPDRS III score: basal 40.4 +/- 11.1, first month 41.1 +/- 10.8;
      final visit, 37.7 +/- 13.3). Two patients (20%) suffered a slight deterioration
      in motor symptoms and another patient suffered deterioration of gait. No analytic
      alterations or serious adverse effects that could limit the use of ziprasidone
      were observed. Although controlled trials are needed, the findings suggest that
      ziprasidone may be effective in parkinsonian patients with psychosis.

PMID- 15965309
TI  - Entacapone increases levodopa exposure and reduces plasma levodopa variability
      when used with Sinemet CR.
AB  - Entacapone is a catechol-O-methyltransferase (COMT) inhibitor used as an adjunct
      to levodopa/dopa decarboxylase inhibitors in the treatment of Parkinson's
      disease. Entacapone increases the bioavailability and reduces the daily variation
      of plasma levodopa when administered with standard levodopa preparations. These
      parameters were studied when entacapone was administered with a controlled
      release levodopa preparation after repeated administrations throughout the day in
      16 healthy male volunteers. On 2 test days, 200 mg entacapone or placebo was
      administered 4 times during the day at 4-hour intervals concomitantly with a
      single dose of controlled-release levodopa/carbidopa 100 mg/25 mg (Sinemet CR).
      Plasma levodopa, 3-O-methyldopa (3-OMD), and carbidopa concentrations were
      measured before intake of the medication and then every 30 minutes for 16 hours
      (until midnight), and less frequently up to 24 hours after the first levodopa
      dose. The minimum, maximum, and average concentration of levodopa; the daily
      variation of levodopa concentration; and the area under the time concentration
      curve (AUC) were calculated. The mean (+/-SD) plasma levodopa AUC was 39% (P =
      0.0001) higher with entacapone (11,802 +/- 1454 ng/hour/mL) compared with placebo
      (8465 +/- 927 ng/hour/mL). The daily variation of plasma levodopa was reduced by
      about 25% with entacapone (P < 0.01). Entacapone significantly reduced plasma 3
      OMD concentration by about 50% (P = 0.0001), indicating marked COMT inhibiting
      activity. There were no differences in plasma carbidopa concentrations.
      Entacapone significantly increased the bioavailability of levodopa and reduced
      its daily variation when administered concomitantly with a controlled-release
      levodopa preparation.

PMID- 15965310
TI  - Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate
      Parkinson disease.
AB  - The primary objective of this study was to describe the pharmacokinetics of oral
      pergolide in patients with mild to moderate Parkinson disease using a new high
      performance liquid chromatography-tandem mass spectrometry assay. A secondary
      objective was to investigate the relationship between plasma concentrations and
      efficacy. Fourteen patients with a diagnosis of Parkinson disease completed this
      multicenter, open-label, dose-escalating study. Pergolide was administered for 58
      days, using increasing daily doses from 0.05 mg daily up to 1 mg three times
      daily and then tapering the dose. The steady-state pharmacokinetic profile and
      motor score were determined at dose levels of 0.25, 0.5, and 1 mg three times a
      day and during elimination after the last dose. Pergolide was absorbed with a
      median time to maximum concentration of 2 to 3 hours across the dose range.
      Systemic exposure appeared to increase proportionally with dose over the range of
      0.25 to 1 mg three times daily within a patient, but there was a large
      variability in exposures between patients (interpatient coefficients of variation
      were 56.4% for the area under the curve). Pergolide was widely distributed
      (volume of distribution, approximately 14,000 L) and was eliminated with a mean
      half-life of 21 hours. Motor scores improved as both peak plasma pergolide
      concentrations and exposure increased. No unexpected safety concerns were
      identified. Pergolide is absorbed relatively quickly into the systemic
      circulation, has a large apparent volume of distribution, and has a relatively
      long half-life (mean, 21 hours). This prolonged half-life is of particular
      interest, given the current hypothesis that more continuous dopaminergic receptor
      stimulation may reduce motor complications in patients with Parkinson disease.

PMID- 15965311
TI  - Safety, tolerability, and changes in amyloid beta concentrations after
      administration of a gamma-secretase inhibitor in volunteers.
AB  - Amyloid beta (Abeta) may play a central role in the pathogenesis of Alzheimer
      disease. A functional gamma-secretase inhibitor, LY450139, was developed that
      inhibits Abeta formation in whole cell assays, transgenic mice, and beagle dogs.
      The authors wished to determine the safety and tolerability of this drug, and the
      reduction of Abeta in plasma and cerebrospinal fluid (CSF) after multiple doses.
      Volunteer subjects (N = 37) were studied using doses from 5 to 50 mg/day given
      for 14 days. Plasma and CSF concentrations of LY450139, Abeta(1-40) and Abeta(1
      X) ("Abeta(total)") were determined, and safety and tolerability were assessed.
      The plasma half-life of LY450139 was approximately 2.5 hours. Pharmacokinetic
      analyses showed a linear relationship between dose and plasma concentrations,
      with a Cmax of 828 +/- 19.2 ng/mL after a 50-mg dose. Plasma Abeta concentrations
      decreased in a dose-dependent manner over a 6-hour interval following drug
      administration, with a maximum decrease of approximately 40% relative to
      baseline. After returning to baseline, Abeta concentrations were transiently
      increased. CSF Abeta concentrations were unchanged. Adverse events reported by
      subjects taking 5-mg, 20-mg, or 40-mg doses were similar to those reported by
      subjects taking placebo. Two of 7 subjects taking 50 mg/day experienced adverse
      events that may have been drug related. In this phase 1 volunteer study, reported
      adverse events after taking LY450139 were manageable. A dose-dependent reduction
      in plasma Abeta was demonstrated, and changes in plasma Abeta concentrations were
      temporally related to the pharmacokinetic characteristics of LY450139.

PMID- 15965312
TI  - Quetiapine-associated depression in a patient with schizophrenia.
AB  - Depression has been reported as a side effect of a wide variety of drugs in
      clinical medicine. Neuroleptics may cause depression in persons with or without
      any past history of psychiatric illness. Clinically, these drug-induced
      depressions may go unnoticed and thus create therapeutic problems. The authors
      present a case of quetiapine-associated depression in a patient being treated for
      schizophrenia. To the best of our knowledge it is the first description of
      depression associated with quetiapine treatment. This case report suggests that
      atypical antipsychotics may be a cause of depression. This is noteworthy because
      these medications have been found in the past to have an antidepressant action.
      Further data based on controlled studies are needed.

PMID- 15965313
TI  - Combination treatment of clozapine and topiramate in resistant rapid-cycling
      bipolar disorder.
AB  - Several open-label studies or case reports have suggested the effectiveness of
      clozapine or topiramate in the treatment of resistant rapid-cycling bipolar
      patients, but none of these publications report the long-term effectiveness of
      these two agents in combination. The authors present a 38-year-old woman with a
      22-year history of rapid-cycling bipolar I disorder who failed to respond
      satisfactorily to various somatic therapies, including combination therapy for
      complex regimens and a course of bilateral electroconvulsive therapy, but finally
      responded well to a combination treatment of clozapine and topiramate. Such a
      combination therapy led the patient to a complete remission for more than 3 years
      without inducing side effects such as weight gain, hyperglycemia, type II
      diabetes mellitus, or hyperlipidemia. In addition, she had a weight loss of 12 kg
      over the past 3 years. This case suggests that the combination treatment of
      clozapine and topiramate can be safe and effective in some resistant rapid
      cycling bipolar patients.

PMID- 15965314
TI  - The effect of galantamine added to clozapine on cognition of five patients with
      schizophrenia.
AB  - Although clozapine may be beneficial for the treatment of cognitive dysfunction
      in schizophrenia, it may also impair some cognitive skills as a result of its
      anticholinergic activity. In this case series, the impact of galantamine
      administration on 5 patients with schizophrenia who had been treated with
      clozapine are reported. Neuropsychological assessment was administered before and
      after 8 weeks of 16 mg/d galantamine treatment. In this case series, galantamine
      was well tolerated by all of the patients. Three of the patients were much
      improved in sustained attention tasks. Most of the patients were also improved in
      psychomotor speed and selective attention tasks. Two patients with low
      pretreatment memory scores seemed to also be improved. Our results suggest that
      the possible role of galantamine as a cognitive enhancer in schizophrenia should
      be investigated in controlled trials.

PMID- 15965315
TI  - Hemichorea-hemiballismus may respond to topiramate.
AB  - Topiramate is a broad-spectrum anticonvulsant that is now widely used for adult
      and pediatric epilepsy. In a singular case, topiramate was recently reported to
      benefit vascular hemichorea-hemiballismus. The authors describe three cases of
      hemichorea-hemiballismus, one of vascular etiology and two of metabolic etiology,
      effectively treated with topiramate.

PMID- 15965316
TI  - Olanzapine-induced myoclonic status.
AB  - Olanzapine-related seizures have rarely been reported despite its proconvulsant
      risk. This is the first description of myoclonic status induced by this
      antipsychotic. A 54-year-old woman with probable Alzheimer disease developed
      continuous myoclonic jerks just after adding olanzapine for neuropsychiatric
      symptoms. She was already receiving citalopram and donepezil at low doses. Jerks
      coincided with spikes and polyspike/wave complexes on EEG. Olanzapine was
      immediately suspended and the seizures subsided. A control EEG showed no
      paroxysmal discharges. Several months later she was given haloperidol and she
      remained seizure free. Olanzapine shares some pharmacologic similarities with
      clozapine, a neuroleptic with a high risk of dose-dependent seizures. This
      adverse effect should be taken into account, and olanzapine should be used with
      caution if concomitant circumstances could decrease the seizure threshold.

PMID- 15965318
TI  - Guillain-Barre-like syndrome associated with olanzapine hypersensitivity
      reaction.
AB  - Olanzapine is the most commonly prescribed atypical antipsychotic drug. Recently
      there has been increased concern over possible adverse metabolic effects of this
      drug. The authors describe the first case of Guillain-Barre-like syndrome
      associated with an olanzapine hypersensitivity reaction. The presence of
      progressive numbness, motor weakness, or pain in the limbs of patients receiving
      olanzapine should raise suspicion of Guillain-Barre syndrome.

PMID- 15965317
TI  - Deterioration of Kearns-Sayre syndrome following articaine administration for
      local anesthesia.
AB  - Worsening of the neuromuscular manifestations in Kearns-Sayre syndrome after
      administering local anesthesia with articaine has not been reported. The authors
      describe a severe adverse reaction to local anesthesia with articaine for tooth
      extraction in a 28-year-old woman with Kearns-Sayre syndrome due to a 5.9-kb
      mitochondrial DNA deletion. The patient was subjected to local anesthesia with
      1.5 mL (60 mg) articaine in the left submandibular nerve for tooth extraction.
      Five minutes after the injection the patient developed weakness of the limb
      muscles, extreme fatigue with increased desire to sleep, a feeling of heat,
      inappetence, and frequent urination. The adverse reaction resolved spontaneously
      within 48 hours without sequelae. Administration of articaine may cause severe
      side effects in patients with Kearns-Sayre syndrome. Articaine should be used
      with caution in these patients.

PMID- 15965319
TI  - Severe skin reaction related to mycophenolate mofetil for myasthenia gravis.
AB  - The authors report the development of a papulosquamous psoriatic-like skin
      eruption following the introduction of mycophenolate mofetil (MM) in a patient
      with myasthenia gravis (MG). MM is a novel and potent immunosuppressive agent
      that blocks purine synthesis, thus selectively inhibiting T and B lymphocyte
      proliferation. Favorable results in refractory and steroid-dependent MG patients
      have been reported in open-label studies, revealing a rapid onset of action and a
      safe side effect profile. Drug eruption due to toxicity or immune-mediated damage
      has not been reported in association with MM. A 32-year-old man with generalized
      seropositive MG with a highly malignant clinical course was admitted to the
      authors' department due to an acute papulosquamous, psoriatic-like skin eruption
      1 month following treatment initiation with MM. Skin biopsy revealed sparse
      perivascular infiltrate of lymphocytes intermingled with few eosinophils.
      Treatment with high-dose steroids together with discontinuation of MM induced a
      gradual improvement, with complete resolution of the symptoms 2 months later. A
      severe and fulminant skin eruption in association with MM treatment is described
      for the first time in the literature. The histopathologic diagnosis of "drug
      eruption" is supported by the resolution of symptoms following discontinuation of
      MM. However, other possibilities include an immune-mediated process supported by
      the presence of lymphocytic infiltrations, the clinical appearance and the
      distribution of lesions (simulating a psoriatic-like dermatitis), as well as the
      marked response to steroids.

PMID- 15965320
TI  - Intrathyroidal parathyroid adenoma.
AB  - A 54-year-old woman was referred for imaging studies after presentation for
      palpitations and a palpable thyroid nodule. The patient underwent a dual-phase
      single-agent Tc-99m sestamibi scan followed later by a thyroid ultrasound at an
      outside hospital. The Tc-99m sestamibi scan showed a marked focus of activity
      separate from the thyroid bed in the inferior left neck. Thyroid ultrasound
      showed a dominant calcified nodule in the left lobe of the thyroid, measuring 1.3
      cm, as well as 3-mm cystic lesions in both lobes of the thyroid. Also, an iodine
      123 scan was performed showing a cold nodule in the left inferior thyroid. During
      surgery, the patient underwent a left thyroid lobectomy for an intrathyroidal
      parathyroid adenoma.

PMID- 15965321
TI  - Incremental value of fusion imaging with integrated PET-CT in oncology.
AB  - PURPOSE: The purpose of this study was to assess the incremental value of
      integrated F-18 FDG PET-CT imaging compared with either alone for evaluation of
      patients with body malignancies. MATERIALS AND METHODS: Images from 173
      consecutive patients with body malignancies referred for integrated PET-CT
      imaging were reviewed. A CT with contrast performed within 2 months of PET-CT was
      available for 74 patients. RESULTS: There was agreement between the transmission
      CT (TrCT) and PET interpreted separately in 65% (112 of 173) of patients.
      Interpretation of integrated PET-CT had an incremental diagnostic value in 17.9%
      (31 of 173) of the total patient population. Data was analyzed further excluding
      patients for whom further analysis was not relevant: 1) 20% (34 of 173) of
      patients with normal TrCT and PET and 2) 11% (19 of 173) of patients with
      disseminated metastases (too numerous to count) on both TrCT and PET. Among the
      120 other patients, PET interpreted alone was positive in 195 body regions and CT
      positive in 178 body regions with agreement for all regions in 49% (59 of 120) of
      patients and discordance or equivocal lesions in 51% (61 of 120) of patients.
      Integrated PET-CT had an incremental diagnostic value in 27% (31 of 120) of
      patients. Contrasted CT scan demonstrated hepatic lesions in 5 and extrahepatic
      lesions in 3 patients overlooked on TrCT; all 8 of these lesions were PET
      positive. There was incremental impact on the management of 12.5% (15 of 120) of
      patients. CONCLUSIONS: After excluding patients with a normal PET-CT or
      disseminated disease, there was an incremental diagnostic value of integrated PET
      CT imaging in 27% (31 of 120) and incremental impact on management in 12.5% (15
      of 120) of patients. CT with contrast did not demonstrate lesions not appreciated
      by PET-CT.

PMID- 15965323
TI  - Intraductal papilloma of the breast: F-18 FDG PET demonstration.

PMID- 15965322
TI  - High-grade lymphoma of the bladder visualized on PET.
AB  - F-18 FDG PET is used for the staging of many cancers. One of its limits is the
      analysis of the pelvis and the urinary tract because of physiological radiotracer
      excretion. We report a rare case of an 82-year-old woman in whom intravenous
      administration of diuretics (furosemide) allowed the identification of a primary
      diffuse large B-cell lymphoma of the bladder wall. This pharmaceutical increases
      urine flow and, therefore, reduces the concentration of radiotracer in the
      urinary tract, improving the visualization of pelvic or urinary tumors.
      Furosemide administration is an easy, safe, and noninvasive method, even in case
      of renal insufficiency. Newer PET cameras with high-performance crystals allow
      rapid acquisitions and improve the tolerance of an examination with diuretic
      injection. The 3-dimensional reconstruction of images in new PET cameras reduces
      the occurrence of hyperactive bladder artifacts. The present case illustrates the
      advantages of furosemide in a rare pathologic entity.

PMID- 15965324
TI  - F-18 FDG PET-CT imaging of a mycotic aneurysm.

PMID- 15965325
TI  - Localization of intestinal bleeding using a fusion of Tc-99m-labeled RBC SPECT
      and X-ray CT.

PMID- 15965326
TI  - Primary lymphoma of the small bowel detected with red blood cell scintigraphy.

PMID- 15965327
TI  - Naturally formed coronary arterial thrombus detected by In-111 oxine platelet
      imaging.

PMID- 15965328
TI  - Localization of myocardial amyloid deposits in cardiac amyloidosis by Tc-99m
      pyrophosphate myocardial SPECT: implication for medical treatment.

PMID- 15965329
TI  - A case of false-positive myocardial perfusion imaging in a patient with left
      bundle branch block.

PMID- 15965330
TI  - Subcutaneous panniculitis-like T cell lymphoma demonstrated on gallium-67
      scintigraphy.

PMID- 15965331
TI  - Ectopic kidneys as a source of misinterpretation on bone scintigraphy.

PMID- 15965332
TI  - Pelvic horseshoe kidney mimics sacral metastases on bone scan.

PMID- 15965333
TI  - Demonstration of vesicorectal fistula on renal scan.

PMID- 15965334
TI  - Serendipitous gallbladder uptake in a bone scan.

PMID- 15965335
TI  - Tc-99m MDP uptake by adrenal metastases from nonsmall cell carcinoma of the lung.

PMID- 15965336
TI  - Characteristic appearance on bone scintigraphy of a 'stone man'.

PMID- 15965337
TI  - F-18 FDG and F-18 FDOPA PET brain imaging in subacute sclerosing panencephalitis.

PMID- 15965338
TI  - Ventilation-perfusion mismatch resulting from an aberrant systemic arterial
      supply to Basal segments of the right lung.

PMID- 15965339
TI  - Primary intrathoracic goiter on scintigraphy.

PMID- 15965340
TI  - Lower extremity schwannoma: F-18 FDG PET and MR demonstration.

PMID- 15965341
TI  - Transient false-negative tc-99m sestamibi parathyroid scintigraphy following
      total thyroidectomy.

PMID- 15965343
TI  - Current readings in nuclear medicine.

PMID- 15965342
TI  - Primary hepatic carcinoid tumor presenting as a large multicystic lesion of the
      liver and on Tc-99m RBC abdominal imaging showing photopenic areas.

PMID- 15965346
TI  - The road to recovery: nutrition counseling for clients in rehab programs.

PMID- 15965347
TI  - The hydration cart: one way to help ensure adequate fluid intake.

PMID- 15965348
TI  - Combination therapy with cerivastatin and nifedipine improves endothelial
      dysfunction after balloon injury in porcine coronary arteries.
AB  - HMG-CoA reductase inhibitors and calcium channel blockers have antiatherogenic
      effects; however, their mechanisms remain to be elucidated. This study examined
      the effect of cerivastatin and/or nifedipine on the endothelial dysfunction in
      porcine balloon-injured coronary arteries. Normal male pigs were randomly divided
      into the following four groups: control, cerivastatin (1 mg/kg/d PO), nifedipine
      (4 mg/kg/d PO), and their combination (n = 10 each). We started the treatments 3
      days before balloon injury in the proximal left coronary arteries and continued
      for 4 weeks after the procedure. Then, we examined endothelial vasodilator
      functions ex vivo in organ chambers and in vitro by Western blotting for eNOS
      expression. Endothelium-dependent relaxations to serotonin, but not those to
      bradykinin or the calcium ionophore A23187 or endothelium-independent relaxations
      to sodium nitroprusside, were significantly impaired by balloon injury. The
      monotherapy with cerivastatin or nifedipine partially improved, and their
      combination supernormalized the relaxations to serotonin without affecting those
      to bradykinin or A23187 or endothelium-independent relaxations to sodium
      nitroprusside. The expression of eNOS was significantly reduced by balloon injury
      and normalized by the combination therapy. These results indicate that the
      combination therapy improves endothelial dysfunction after balloon injury, in
      which the up-regulation of eNOS may be involved.

PMID- 15965349
TI  - Blocking characteristics of hKv1.5 and hKv4.3/hKChIP2.2 after administration of
      the novel antiarrhythmic compound AZD7009.
AB  - AZD7009 is a novel antiarrhythmic compound in early clinical development for
      management of atrial fibrillation. Electrophysiological studies in animals have
      shown high antiarrhythmic efficacy, predominant action on atrial
      electrophysiology, and low proarrhythmic activity. AZD7009 has previously been
      shown to inhibit hERG and hNav1.5 currents. The main objective of the present
      study was to characterize the effects of AZD7009 on hKv1.5 and hKv4.3/hKChIP2.2
      currents to get a deeper understanding of the ion channel-blocking properties of
      the compound. hKv1.5 and hKv4.3/hKChIP2.2 currents were expressed in CHO cells.
      Currents were measured using the whole-cell configuration of the voltage-clamp
      technique. AZD7009 inhibited hKv1.5 and hKv4.3/hKChIP2.2 currents with equal
      potency: the IC50 for hKv1.5 block was 27.0 +/- 1.6 muM (n = 6), and the IC50 for
      hKv4.3/hKChIP2.2 block was 23.7 +/- 4.4 muM (n = 5). Block of the
      hKv4.3/hKChIP2.2 current was frequency dependent with larger block at higher
      frequency, whereas block of the hKv1.5 current was slightly decreased at higher
      frequency. In conclusion, AZD7009 inhibits both the hKv1.5 and the
      hKv4.3/hKChIP2.2 currents. These effects likely contribute to the effects
      described in animals in vivo.

PMID- 15965350
TI  - Paradoxical effects of fenofibrate and nicotinic acid in apo E-deficient mice.
AB  - Atherosclerosis is a complex vascular disease initiated by abnormal accumulation
      of plasma lipoproteins in the subendothelial space. Elevated levels of plasma
      triglycerides (TG) and low-density lipoprotein (LDL)-cholesterol as well as low
      concentrations of high-density lipoprotein (HDL) play a causal role in the
      development and progression of atherosclerotic lesions. We have shown that
      apolipoprotein E-deficient (apo E-KO) mice have elevated triglyceride levels plus
      diminished HDL concentrations. Drugs such as fenofibrate and nicotinic acid are
      well known to reduce TG and increase HDL levels in humans. In this study, we
      investigated the beneficial effects of fenofibrate and niacin on lipid profile
      and atherogenesis in apo E-KO mice and their wild-type counterparts. Animals were
      fed with a cholesterol-enriched diet supplemented with fenofibrate (0.1% wt/wt, n
      = 8) or nicotinic acid (0.5% wt/wt, n = 8) for 14 weeks. Body weights were
      recorded weekly, and plasma lipid profiles were determined at 4-week intervals.
      The hearts and aortas were collected and fixed for histologic and morphometric
      evaluations of atherosclerotic lesions. Fenofibrate treatment in apo E-KO mice
      paradoxically increased total cholesterol and TG by 65% and 44%, respectively,
      and decreased HDL-cholesterol levels by 35% as compared with controls. Similar
      effects of fenofibrate on cholesterol levels, but not on TG concentrations, were
      observed in C57BL/6 mice. Fenofibrate-treated mice had lower body weight as
      compared with controls. Niacin had no effect on body weight gain but failed to
      decrease TG or to increase HDL levels in either apo E-KO mice or their wild-type
      counterparts. Neither fenofibrate nor niacin significantly influenced
      atherogenesis in apo E-KO mice as compared with controls. In conclusion, this
      study shows that neither niacin nor fenofibrate has beneficial lipid-modifying
      and antiatherosclerosis activities in mice. Identification of mechanisms
      underlying paradoxical effects of fenofibrate on lipoprotein metabolisms in apo E
      KO mice merits further investigation.

PMID- 15965351
TI  - Estradiol metabolites attenuate renal and cardiovascular injury induced by
      chronic nitric oxide synthase inhibition.
AB  - Our previous studies in rodent models of nephropathy demonstrate that 2
      hydroxyestradiol (2HE), an estradiol metabolite with little estrogenic activity,
      exerts renoprotective effects. In vivo, 2HE is readily converted to 2
      methoxyestradiol (2ME), a major estradiol metabolite with no estrogenic activity.
      The goal of this study was to determine whether 2ME has renal and cardiovascular
      protective effects in vivo. First, the acute (90 minutes) and chronic (14 days)
      effects of 2ME (10 microg/kg/h) on blood pressure and renal function were
      examined in normotensive and spontaneously hypertensive rats (SHR). Second, a rat
      model of cardiovascular and renal injury induced by chronic nitric oxide synthase
      inhibition (N-nitro-L-arginine; 40 mg/kg/d; LNNA group) was used to examine the
      protective effects of estradiol metabolites. Subsets of LNNA-treated rats were
      administered either 2HE or 2ME (10 microg/kg/h via osmotic minipump; LNNA+2ME and
      LNNA+2HE groups, respectively. 2-Methoxyestradiol had no acute or chronic effects
      on blood pressure or renal function in normotensive animals or on hypertension in
      SHR. Prolonged, 5-week NOS inhibition induced severe cardiovascular and renal
      disease and high mortality (75%, LNNA group). 2ME, but not 2HE, significantly
      decreased elevated blood pressure and attenuated the reduction in GFR. 2HE
      delayed the onset of proteinuria, whereas no proteinuria was detected in the 2-ME
      group. 2HE and 2ME reduced mortality rate by 66% and 83%, respectively (P <
      0.001). In the kidney, 2HE and 2ME abolished LNNA-induced interstitial and
      glomerular inflammation, attenuated glomerular collagen IV synthesis, and
      inhibited glomerular and tubular cell proliferation. In the heart, 2HE and 2ME
      markedly reduced vascular and interstitial inflammation and reduced collagen
      synthesis and vascular/interstitial cell proliferation. This study provides the
      first evidence that, in a model of severe cardiovascular and renal injury, 2
      methoxyestradiol (a major nonestrogenic estradiol metabolite) exerts renal and
      cardiovascular protective effects and reduces mortality.

PMID- 15965352
TI  - Chronic treatment with flavonoids prevents endothelial dysfunction in
      spontaneously hypertensive rat aorta.
AB  - Flavonoids are known to possess cardioprotective properties. Vascular endothelial
      function is a surrogate marker for cardiovascular diseases, including
      hypertension. We have studied the effects of chronic flavonoid treatment on
      vascular endothelial functions in spontaneously hypertensive rats (SHR). Starting
      from 6-7 weeks old, SHR were given flavonoids (baicalein, flavone, or quercetin)
      orally (10 mg/kg, once daily) to the SHRs for 4 weeks. Aortas from all the
      flavonoid-treated animals showed remarkably higher endothelium-dependent
      relaxations to acetylcholine, to a similar extent as those pretreated with the
      angiotensin-converting enzyme inhibitor, captopril. However, in contrast to other
      experimental groups, flavone pretreatment also enhanced the endothelium
      independent relaxations to sodium nitroprusside. In addition, treatment with
      either flavone or quercetin induced a significant attenuation in systolic blood
      pressure of the hypertensive animals. The present results suggest that chronic
      treatment with the flavonoids (baicalein, flavone, and quercetin) preserves
      vascular endothelial functions in hypertensive animals through several possible
      actions, including increasing endothelial nitric oxide production and
      bioavailability and reduction in blood pressure.

PMID- 15965353
TI  - Variation in the ability of glycoprotein IIb-IIIa antagonists to exert and
      maintain their inhibitory effects on the binding of fibrinogen.
AB  - Tirofiban and eptifibatide dissociate rapidly from glycoprotein IIb-IIIa but have
      different dissociation constants (KD of tirofiban = 15 nmol/L, that of
      eptifibatide = 120 nmol/L). Binding of fibrinogen to glycoprotein IIb-IIIa is
      biphasic, forming an initial reversible complex (KD = 155-180 nmol/L) and a
      second more stable complex (KD = 20-70 nmol/L). To test whether a comparable
      extent of inhibition would be maintained by pharmacologic antagonists that
      exhibit a rapid rate of release, blood from 26 patients with symptomatic coronary
      artery disease was added to reaction tubes containing a concentration of either
      agent that had been shown to achieve optimal inhibition (for tirofiban 100 ng/mL,
      for eptifibatide 1.7 microg/mL) plus a platelet agonist (1 microM adenosine
      diphosphate [ADP] or 25 microM thrombin receptor agonist peptide [TRAP]), and
      fluorochrome labeled fibrinogen before analysis by flow cytometry. The extent of
      inhibition early on (30 seconds to 3 minutes) was similar. By contrast, the
      extent of inhibition 10 to 15 minutes later was maintained more effectively with
      tirofiban than eptifibatide (difference in slope P < 0.01). The differences are
      consistent with the biphasic binding of fibrinogen to GP IIb-IIIa. The clinical
      implications of this observation merit evaluation to potentially improve care of
      patients and to guide future drug development.

PMID- 15965354
TI  - Edaravone prevented deteriorated cardiac function after myocardial ischemia
      reperfusion via inhibiting lipid peroxidation in rat.
AB  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) has potent effects in the brain
      as a free radical scavenger in ischemia-reperfusion as well as in ischemic
      injuries. However, whether this free radical scavenger prevents deterioration of
      cardiac function and lethal ventricular arrhythmias after ischemia-reperfusion in
      rat heart is not clear. We aimed to assess whether free radical scavenging by
      edaravone maintains cardiac function and suppresses life-threatening ventricular
      tachyarrhythmia after myocardial ischemia-reperfusion. Twenty-nine 7-week-old
      male Sprague-Dawley rats had acute myocardial ischemia induced by ligation of the
      left coronary artery for 5 minutes followed by reperfusion. Eleven were treated
      by intravenous injection of edaravone at 3 mg/kg 2 minutes after coronary
      ligation, and 18 were left untreated. The index of systolic function
      (contractility; end-systolic elastance, Ees) and hemodynamics were measured by
      pressure-volume relationships every 5 minutes before ligation to 25 minutes after
      reperfusion. Blood levels of malondialdehyde (MDA) and the ischemic areas were
      also measured 25 minutes after reperfusion. There were no differences in the
      ischemic areas between the groups. Lethal reperfusion tachyarrhythmia was
      observed in 5 untreated rats but not in those having edaravone treatment. Ees was
      significantly greater in the edaravone-treated than in untreated rats from 5 to
      25 minutes after reperfusion (1789 +/- 866 in untreated versus 2809 +/- 273 mm
      Hg/mL in edaravone-treated rats at 25 minutes, P < 0.001). MDA level was
      significantly lower in edaravone-treated than in untreated rats (1.44 +/- 0.29
      nmol/L in edaravone-treated versus 1.90 +/- 0.28 nmol/L in untreated group, P <
      0.05). The results suggest that edaravone treatment before reperfusion prevented
      lethal reperfusion ventricular tachyarrhythmias and deteriorated cardiac function
      with ischemia and ischemia-reperfusion injuries through inhibiting lipid
      peroxidation in terms of scavenging for free radicals.

PMID- 15965356
TI  - Effects of the long-term administration of nicorandil on vascular endothelial
      function and the progression of arteriosclerosis.
AB  - This study compared the effects of long-term administration of nicorandil and
      isosorbide dinitrate (ISDN) on vascular endothelial function and the progression
      of arteriosclerosis. Forty-two patients with ischemic heart disease were randomly
      allocated to receive nicorandil (N group; 15 mg/d) or ISDN (I group, 40 mg/d).
      Twelve normal subjects served as controls. Vascular endothelial function and the
      progression of arteriosclerosis (intima-media thickness, IMT), as determined by
      carotid vascular ultrasound, were assessed 1 week before and 3 months after drug
      administration. Reactive hyperemia was induced in the forearm for 5 minutes, and
      the percentage change in the diameter of the brachial artery (% change in flow
      mediated dilation, %FMD) was calculated. FMD was significantly lower in CAD
      groups than in controls. The %FMD significantly decreased (7.2 +/- 1.9 to 4.2 +/-
      2.8) in the I group, while rising from 6.8 +/- 1.6 to 8.0 +/- 2.0 in the N group.
      IMT increased by 0.036 +/- 0.015 mm in the I group but showed no significant
      change in the N group (-0.01 +/- 0.012 mm). Thus, ISDN deteriorates IMT and FMD,
      whereas a beneficial effect of nicorandil is seen on FMD with no effect on IMT.
      Long-term treatment with nicorandil may be desirable for prevention of
      cardiovascular events.

PMID- 15965357
TI  - Novel method to assess cardiac electrophysiology in the rat: characterization of
      standard ion channel blockers.
AB  - The rat continues to be an important tool to assess cardiac electrophysiologic
      (EP) effects of test agents and to study the distribution/role of ion channels in
      cardiovascular diseases. However, no data have been described that accurately
      measure discrete cardiac EP parameters in rats in vivo. Therefore, we developed a
      method to assess cardiac EP in rats and then profiled several ion channel agents.
      Briefly, rats were instrumented with endocardially placed electrodes to assess
      cardiac refractoriness and conduction. Administration of class I agents resulted
      in a dose-dependent slowing of ventricular conduction. The potassium channel
      blocker 4-aminopyridine caused significant increases in atrial and ventricular
      refractoriness. An IKr blocker had little or no effect on atrial and ventricular
      refractoriness but significantly increased AV nodal refractoriness. Additionally,
      an IKs blocker had little effect on rat cardiac EP. The L-type blocker diltiazem
      caused a dose-dependent delay in AV node conduction and an increase in AV node
      refractoriness. Overall, this study provides normative data that describe the
      roles of Na, Ca, and K channels in rat cardiac electrophysiology, in vivo.
      Furthermore, the model provides a method to assess changes in cardiac
      electrophysiology in the setting of disease by using well-established rat models
      of induced or genetic cardiovascular disease.

PMID- 15965355
TI  - Neuronal norepinephrine responses of the rostral ventrolateral medulla and
      nucleus tractus solitarius neurons distinguish the I1- from the alpha2-receptor
      mediated hypotension in conscious SHRs.
AB  - We tested the hypothesis that the I1 receptor mediates the reduction in rostral
      ventrolateral medulla (RVLM) neuronal norepinephrine (NE; index of sympathetic
      activity) that leads to hypotension independent of other brainstem areas or the
      alpha2-adrenergic receptor. To this end, we developed a model that permitted
      measurement of real-time changes in neuronal NE in the RVLM or nucleus tractus
      solitarius (NTS) along with blood pressure and heart rate in the conscious SHR in
      response to localized microinjections of selective I1 (rilmenidine) or alpha2
      adrenergic (alpha-methylnorepinephrine; alpha-MNE) agonist versus the mixed
      I1/alpha2 agonist clonidine. To further support the hypothesis, we investigated
      the effects of localized selective alpha2- (SK&F86466) or I1 (efaroxan) blockade
      on the reductions in neuronal NE and blood pressure elicited by intra-RVLM
      rilmenidine. In the latter experiment, changes in RVLM neuronal c-Fos (another
      marker of sympathetic neural activity) were also investigated. Intra-RVLM
      rilmenidine (40 nmol) or clonidine (1 nmol) similarly reduced RVLM NE and blood
      pressure; these responses were approximately 2-fold greater than those elicited
      by the pure alpha2-adrenergic agonist alpha-MNE (10 nmol). By contrast, intra-NTS
      rilmenidine or clonidine had no effect on NTS NE or blood pressure versus
      significant reductions in both parameters by alpha-MNE. Intra-RVLM rilmenidine
      decreased c-Fos expression, and these responses were abolished by efaroxan but
      not by SK&F 86466. These findings suggest: (1) in the RVLM, I1-receptor signaling
      suppresses cardiovascular neuron activity, which leads to lowering of blood
      pressure; (2) although the alpha2-adrenergic receptor in the RVLM serves a
      similar role, it does not exert a tonic neuronal inhibitory effect and is not
      essential, as a downstream signaling entity, for the I1-evoked neurobiological
      effects in the brainstem. The potential confounding effects of anesthetics on the
      I1 and/or alpha2 receptor-mediated neuronal and cardiovascular responses were
      circumvented in the present study.

PMID- 15965358
TI  - Ligands at beta2-, beta3-, and the low-affinity state of beta1-adrenoceptors
      block the alpha1-adrenoceptor-mediated constriction in human pulmonary and rat
      mesenteric arteries.
AB  - We examined whether the beta2-adrenoceptor agonists fenoterol and salbutamol, the
      beta3-adrenoceptor agonists CL 316243 and ZD 2079, and the agonists of the low
      affinity state of beta-adrenoceptors, cyanopindolol and CGP 12177 block alpha1
      adrenoceptors in that concentration range in which they relax the human pulmonary
      and rat mesenteric arteries preconstricted with phenylephrine 10 microM and 1
      microM, respectively. For quantification of vasodilatation pEC25 values and for
      the antagonism toward alpha1-adrenoceptors, pA2 values were determined. We found
      that in the rat mesenteric artery, (1) the pEC25 values of the beta-adrenoceptor
      ligands resemble their respective pA2 values (difference < or = 0.9 log units),
      and (2) the order of potencies is the same for both parameters, ie, cyanopindolol
      approximately fenoterol > CGP 12177 > salbutamol > ZD 2079 > CL 316243. In the
      human pulmonary artery, (1) the pEC25 values are slightly lower (by 0.6-1.3 log
      units) than their respective pA2 values, and (2) the rank order of potencies is
      the same for both parameters. In conclusion, the present study suggests that
      ligands of beta2-adrenoceptors and of non-beta1-non-beta2-adrenoceptors relax rat
      and human vessels preconstricted with phenylephrine or norepinephrine mainly
      through their alpha1-adrenolytic effects. Hence, for the investigation of the
      role of beta-adrenoceptors in vessels, the constrictor agent should be chosen
      with great caution.

PMID- 15965359
TI  - Immediate versus delayed facilitated percutaneous coronary intervention: a pilot
      study.
AB  - The study was aimed to investigate the outcomes in patients initially
      successfully treated pharmacologically and immediate PCI <2 hours, and in
      patients initially successfully treated with pharmacological therapy and delayed
      PCI (12-72 hours). All patients had to have successful reperfusion, to receive
      the combination of a standard abciximab infusion plus half dose rtPA. Similar
      results were observed in both groups. Delayed PCI group showed a favorable trend
      in restenosis and bleedings (ns) and a significant reduced angiographic evidence
      of thrombus formation in IRA. Our very preliminary data suggest the safety and
      possible use of delayed facilitated PCI in patients with STEMI. The studied
      patients have successful reperfusion and TIMI-3 flow and our data may not apply
      to patients with TIMI 0-2 flow.

PMID- 15965360
TI  - The anti-anginal drug trimetazidine reduces neutrophil-mediated cardiac
      reperfusion injury.
AB  - Trimetazidine has no hemodynamic/antithrombotic actions. Hence, its anti-ischemic
      properties have been mostly attributed to its metabolic effects. However, this
      issue is not completely elucidated. We investigated whether inhibition of
      neutrophil activation may also contribute to its cardioprotective action. We
      first showed that trimetazidine inhibits neutrophil activation in vitro. We
      subsequently tested whether trimetazidine protects postischemic hearts from
      neutrophil-mediated injury. Four groups of rat hearts underwent 20 minutes of
      global ischemia: (1) controls, reperfused with neutrophil-enriched buffer for 5
      minutes, followed by 40 minutes standard perfusate; (2) hearts from rats
      pretreated with trimetazidine for 1 week; (3) hearts in which 10 M trimetazidine
      was added to the perfusate, starting 5 minutes before ischemia and for the
      initial 15 minutes of reflow; (4) hearts from pretreated rats that also received
      trimetazidine in the perfusate. Postischemic impairment of contractile function
      was significantly attenuated by trimetazidine infusion (recovery of developed
      pressure: 68 +/- 7% versus 42 +/- 9% of baseline in controls; P < 0.05).
      Pretreatment alone was not effective, nor did it further improve the beneficial
      effects of infusion. Cardiac oxygen radical production at reflow (by electron
      paramagnetic resonance spectroscopy) was also reduced by trimetazidine,
      independently of direct scavenger effects. Thus, trimetazidine can protect
      postischemic hearts from neutrophil-mediated injury.

PMID- 15965361
TI  - Radix angelica elicits both nitric oxide-dependent and calcium influx-mediated
      relaxation in rat aorta.
AB  - This study examined the vascular relaxation produced by Radix Angelica (AG; Dong
      Quai) and its possible mechanisms in isolated rat aortic rings precontracted with
      norepinephrine. The butanolic fraction (AgBt) of the crude extract of AG causes
      gradual endothelium-independent relaxation, which was unaffected by five
      different potassium channel inhibitors. AgBt attenuated the CaCl2-induced
      vasoconstriction in high-potassium depolarized medium; this required less than
      one-tenth the concentration needed to elicit vascular relaxation. An aqueous
      fraction (AgDw) of the crude extract induced transient acute relaxation, which
      was virtually abolished by endothelial ablation and pretreatment with L-NNA. L
      Arginine fully reversed the action of L-NNA. Methylene blue and atropine
      significantly attenuated the relaxation, but indomethacin did not. Ferulic acid,
      the main active component in AG, relaxed both endothelium-intact and -denuded
      rings, while L-NNA, methylene blue, or atropine did not modify the relaxation.
      Ferulic acid also did not attenuate the CaCl2-induced contraction in high
      potassium depolarized medium. In conclusion, Radix Angelica leads to both
      endothelium-dependent and -independent relaxation of isolated rat aorta.
      Increased formation of NO might contribute to the endothelium-mediated
      relaxation, while inhibition of the calcium influx might be an important
      mechanism in direct smooth muscle relaxation. A substance other than ferulic acid
      might create these effects.

PMID- 15965362
TI  - Effects of chloride substitution in isolated mesenteric blood vessels from Dahl
      normotensive and hypertensive rats.
AB  - The purpose of this investigation was to examine the effect of Cl-free medium,
      nitric oxide synthase inhibitor (N nitro-L-arginine methyl ester; L-NAME), and Cl
      channel antagonist (niflumic acid), on alpha1-adrenoceptor (cirazoline) mediated
      responses in the isolated mesenteric blood vessels from Dahl salt-resistant
      normotensive (SRN) and salt-sensitive hypertensive (SSH) rats on a 4% salt diet
      for 7 weeks. Cirazoline produced dose-dependent vasoconstriction in blood vessels
      of SRN and SSH rats. Replacement of extracellular Cl with propionate ions
      significantly inhibited (P < 0.05) cirazoline-mediated vasoconstriction in SRN
      but not in SSH rats. Perfusion with L-NAME (10 microM) augmented responses to
      cirazoline in SRN but not in SSH rats. In Cl-free medium, addition of L-NAME had
      a biphasic effect on cirazoline responses; potentiation of responses at the lower
      doses and attenuation at the highest dose. Niflumic acid (10 microM)
      significantly inhibited cirazoline responses with the inhibition being more
      pronounced in SRN than SSH rats. The resting Em of smooth muscle cells was -68.0
      +/- 4.2 mV (mean +/- SD; n = 87) and -67.2 +/- 4.8 mV (n = 88), in SRN and SSH
      rats, respectively. Perfusion with Cl-free medium produced a significant
      depolarization that was larger in smooth muscle cells of SSH (-57.4 +/- 4.8 mV, n
      = 38) than SRN (-61.3 +/- 5.4 mV, n = 35) rats, while L-NAME depolarized the
      smooth muscle cells of SRN (-62.1 +/- 6.5 mV, n = 36) but not SSH (-67.5 +/- 4.2
      mV, n = 34) rats. The data supports the view that Cl handling and Ca-dependent Cl
      channels seem to undergo modification as a consequence of salt-induced
      hypertension. It is also possible that the modified role of nitric oxide on
      membrane potential may have a direct bearing on the changes observed in Cl
      handling in blood vessels of SRN versus SSH rats.

PMID- 15965363
TI  - Compensation of endothelium-dependent responses in coronary circulation of eNOS
      deficient mice.
AB  - Nitric oxide plays a fundamental role in the regulation of blood flow. Here we
      analyzed compensatory mechanisms for the genetic eNOS deficiency in aorta and in
      coronary circulation. Vasodilation induced by acetylcholine, bradykinin,
      adenosine, and ADP as well as by S-nitroso-penicillamine (SNAP) was assessed in
      isolated aorta and in isolated mouse hearts from eNOS-/- and age-matched eNOS+/+
      mice. In aorta from eNOS+/+ mice acetylcholine-induced vasodilation was entirely
      dependent on NO, and this response was absent in aorta from eNOS-/- mice. In
      eNOS+/+ mouse hearts responses induced by bradykinin, adenosine and ADP were
      partially dependent on NO, but not on PGI2, cytochrome P450-dependent
      metabolites, or H2O2. On the other hand, vasodilation induced by acetylcholine
      involved NO, but not PGI2, in its immediate, short-lasting phase, whereas PGI2
      and NO mediated delayed, longer-lasting phase of this response. In eNOS-/- mouse
      hearts coronary vasodilator function was compensated. Responses induced by
      acetylcholine and adenosine, but not by bradykinin or ADP, were in part
      compensated by NO, most likely derived from nNOS. However, the major mechanisms
      compensating for the loss of eNOS in the coronary circulation did not rely on NO,
      PGI2, cytochrome P450-derived metabolites of arachidonic acid or on H2O2.
      Deficiency of eNOS is largely compensated in coronary circulation but not in
      aorta.

PMID- 15965364
TI  - Making medication administration safe: report challenges nurses to lead the way.

PMID- 15965365
TI  - Executive summary: the state of the science on safe medication administration
      symposium.

PMID- 15965366
TI  - How we think about medication errors: a model and a charge for nurses.

PMID- 15965367
TI  - Errors from the consumer's perspective: tragedy motivated one woman to take
      action.

PMID- 15965368
TI  - Medication errors: why they happen, and how they can be prevented.

PMID- 15965369
TI  - Toward safer IV medication administration: the narrow safety margins of many IV
      medications make this route particularly dangerous.

PMID- 15965370
TI  - Medication reconciliation: transfer of medication information across settings
      keeping it free from error.

PMID- 15965371
TI  - Technology and safe medication administration.

PMID- 15965372
TI  - Discussion & recommendations: safe medication administration: an invitational
      symposium recommends ways of addressing obstacles.

PMID- 15965373
TI  - State of the science on safe medication administration. Proceedings of an
      invitational symposium. July 16-17, 2004. Philadelphia, Pennsylvania, USA.

PMID- 15965375
TI  - Diagnostic tools and therapeutic interventions that may influence the integrity
      of vascular and nonvascular access devices.
AB  - Current technology introduces many new vascular and nonvascular devices to the
      medical field. With the assistance of these devices, patients can be offered many
      more diagnostic tests and therapeutic treatments that aid in the diagnosis and
      treatment of diseases. As with any new infusion technology, these devices can be
      associated with complications attributable to the rapid rate of infusion. This
      article defines vascular and nonvascular devices; describes diagnostic
      medication, tests, and treatments that may have an impact on outcome or
      compromise vascular access; and describes the role of nurses and radiologic
      technicians in preventing complications related to vascular access.

PMID- 15965376
TI  - Legal issues related to vascular access devices and infusion therapy.
AB  - Infusion therapies are being delivered in many healthcare settings including
      hospitals, homecare settings, long-term care facilities, occupational health
      facilities, outpatient units, and physician offices. Nurses who infuse
      medications must be properly educated to recognize vascular access complications
      and initiate the proper interventions. This article discusses the high-risk areas
      of nursing malpractice related to infusion therapies.

PMID- 15965377
TI  - Cost containment and infusion services.
AB  - The implementation of the Medicare Prospective Payment System (MPPS) has placed
      pressure on healthcare organizations to decrease patient length of stay without
      adversely affecting outcomes. This article discusses the impact of the MPPS on
      clinicians who provide infusion therapy, and examines methods for containing
      costs related to infusion care such as advanced planning and accurate vascular
      access device selection.

PMID- 15965380
TI  - Innovations in central vascular access device insertion.
AB  - The new millennium has brought with it many technological advances that have
      affected every industry, especially healthcare and nursing. The key to success
      will be the ability of nurses to acclimate to these changes. To accomplish this,
      nurses need to advance their individual practice and skills, and to pursue and
      maintain an education in their respective fields. At no other time in healthcare
      history have so many changes taken place in such a short time, and nurses must
      remain abreast of changes to ensure career securement, advancement, and the
      safety of their patients. This article focuses on peripherally inserted central
      catheters and the changing technology for their insertion, maintenance, and
      training requirements.

PMID- 15965381
TI  - Patient safety in nursing practice.

PMID- 15965382
TI  - Patient safety: planting the seed.

PMID- 15965383
TI  - Are nursing homes ready to create sustainable improvement?

PMID- 15965384
TI  - Nurse care coordination for diabetes: a literature review and synthesis.

PMID- 15965385
TI  - Nursing informatics approach to analyzing staffing effectiveness indicators.

PMID- 15965386
TI  - A psychometric analysis of the patient satisfaction with nursing care quality
      questionnaire: an actionable approach to measuring patient satisfaction.
AB  - Patient satisfaction with nursing care quality is an important indicator of the
      quality of care provided in hospitals. This study tested a newly developed
      patient-centered measure of patient satisfaction with nursing care quality within
      a random sample of 14 hospitals in Ontario, Canada. Results of this study
      revealed that the newly developed instrument had excellent psychometric
      properties. Total scores on satisfaction with nursing care were strongly related
      to overall satisfaction with the quality of care received during hospitalization.
      The results of this study yielded actionable, patient-focused results that can be
      used by managers to address areas requiring improvement.

PMID- 15965388
TI  - Patient anxiety and patient satisfaction in hospital-based and freestanding
      ambulatory surgery centers.
AB  - The study examined differences in patient anxiety and patient satisfaction
      between patients who experienced surgery at a hospital-based ambulatory surgery
      center versus a freestanding ambulatory surgery center. Forty-seven participants
      completed the State Trait Anxiety Inventory and Press Ganey Ambulatory Surgery
      Survey. Patients at both types of facilities experienced moderate levels of
      preoperative anxiety and were highly satisfied with care received. No significant
      differences were found in preoperative anxiety, overall satisfaction with care,
      or overall satisfaction with nursing care. The site where the surgery was
      performed may not be a determining factor in patient anxiety or satisfaction
      levels.

PMID- 15965387
TI  - Rural African American women's descriptions of mammogram quality.
AB  - The voices of rural women are frequently absent in discussions of quality
      healthcare. This study utilized a phenomenological research design to examine
      rural African American women's descriptions of mammogram quality. Twenty-three
      women in rural Georgia communities were interviewed. Participants desired quality
      mammogram experiences in which they were treated with kindness and respect, were
      given explanations of the mammogram procedure and outcome, and were cared for by
      health professionals who were competent in their roles.

PMID- 15965389
TI  - Delirium: a process improvement approach to changing prescribing practices in a
      community teaching hospital.
AB  - An interdisciplinary continuous process improvement team developed an educational
      intervention for physicians, nurses, and other healthcare professionals that
      focused on the role of medications in the etiology of delirium among hospitalized
      patients aged 65 years and older. An analysis of prescribing practices after the
      educational intervention revealed a reduction in the use for 57% of the drugs
      targeted. Other outcomes from this process improvement methodology are also
      examined.

PMID- 15965391
TI  - Long-term restraint reduction: one hospital's experience with restraint
      alternatives.
AB  - Over the last several years, regulatory bodies have implemented and maintained
      strict standards and regulations regarding the use of restraint in the acute care
      setting. Hospitals have responded by attempting to reduce restraint use and
      increase alternatives to restraint. Our hospital formed a Restraint Reduction
      Task Force, setting a goal to decrease restraint use. This article describes the
      task force's actions, interventions, and findings for the long-term reduction of
      restraint use in a 236-bed community-based hospital setting. Hospital
      administrators have been and continue to be supportive of the initiatives set
      forth by the Restraint Reduction Task Force, which has been a vital component of
      the ongoing restraint reduction efforts in the hospital.

PMID- 15965392
TI  - Developing a pain management program through continuous improvement strategies.
AB  - Pain affects more than one third of cancer patients in the early stages of their
      disease, dramatically rising above 70% in the advanced stages. Numerous studies
      have been conducted in the pursuit of cancer pain relief, yet the prevalence of
      pain persists. This article focuses on a pain management program, developed by a
      performance improvement team, which addressed the inadequacies of current pain
      management. Performance improvement activities are described through the process
      of assessment, planning, implementation, and evaluation of the pain management
      program. This pain management program is uniquely derived from a unit core value
      that all staff is responsible and accountable for pain management.

PMID- 15965393
TI  - Plan, do, study, act model to improve an orientation program.
AB  - The Franciscan Health System has designed a new employee orientation program that
      is both interactive and thought-provoking. The program has transitioned from a
      predominantly lecture-based format to one that consists of group discussion, role
      playing, lunch with senior leaders in the organization, and the utilization of
      adult learning principles. This article describes the shortcomings of the
      previous program, gaps identified in the needs assessment, and performance
      improvement methodology used to enhance the program.

PMID- 15965394
TI  - Evaluation of outcomes: the effects of continuous lateral rotational therapy.
AB  - Research on continuous lateral rotational therapy (CLRT) has demonstrated mixed
      results, but there have been definite benefits described in its use for the
      prevention and treatment of nosocomial and ventilator-acquired pneumonia. Several
      studies have shown decreased hospital and intensive care unit costs and lengths
      of stay, and ventilator days when used appropriately. The intent of this study
      was to develop a protocol for initiating and discontinuing CLRT and to determine
      if the protocol would result in more effective and efficient use of this therapy.

PMID- 15965395
TI  - Work environmental factors and retention of nurses.
AB  - Perceptions of the work environment were studied among acute care nurses working
      in a large county hospital who left their units during an 18-month period,
      compared to those who stayed. Analysis using Moos' work environment subscales
      suggests that the nurses who remained in their units perceived less work pressure
      and had greater perception of peer cohesion, supervisor support, and autonomy
      than nurses who left. Moos' Work Environment Scale suggests that a supportive
      work environment enables nurses to provide quality patient care, enhance their
      own self-esteem, increase job satisfaction, and provide cost savings to their
      employers. Such an environment promotes retention of skilled, caring,
      knowledgeable, and experienced nurses who provide better patient care with fewer
      complications, and reduces the economic and social costs of healthcare for both
      providers and consumers.

PMID- 15965403
TI  - Self-reported nonmusculoskeletal responses to chiropractic intervention: a
      multination survey.
AB  - OBJECTIVE: To replicate a previous study of nonmusculoskeletal responses to
      chiropractic intervention and to establish whether such responses are influenced
      by the country of study, chiropractors' attitudes, and information to patients,
      patients' demographic profiles, and treatment regimens. METHODS: Information
      obtained through questionnaires by chiropractors and patients on return visit
      within 2 weeks of previous treatment from chiropractic practices in Canada,
      United States, Mexico, Hong-Kong, Japan, Australia, and South Africa. In all, 385
      chiropractors collected valid data on 5607 patients. Spinal manipulation with or
      without additional therapy was the intervention provided by chiropractors.
      Outcome measures included self-reported improved nonmusculoskeletal reactions
      (allergy, asthma, breathing, circulation, digestion, hearing, heart function,
      ringing in the ears, sinus problems, urination, and others). RESULTS: The results
      from the previous study were largely reproduced. Positive reactions were reported
      by 2% to 10% of all patients and by 3% to 27% of those who reported to have such
      problems. Most common were improved breathing (27%), digestion (26%), and
      circulation (21%). Some variables were identified that somewhat influenced the
      outcome: patients informed that such reactions may occur (odds ratio [OR] 1.5),
      treatment to the upper cervical spine (OR 1.4), treatment to lower thoracic spine
      (OR 1.3), and female sex (OR 1.3). However, these had a very small "explanatory"
      value (pseudo R2 3%). CONCLUSION: A minority of patients with self-reported
      nonmusculoskeletal symptoms report definite improvement after chiropractic care,
      and very few report definite worsening. Future studies should use stringent
      criteria to investigate a possible treatment effect and concentrate on specific
      diagnostic subgroups such as digestive problems and tinnitus.

PMID- 15965404
TI  - Cervicothoracic angina identified by case history and palpation findings in
      patients with stable angina pectoris.
AB  - OBJECTIVE: To investigate the decision-making process of an experienced
      chiropractor in diagnosing noncardiac musculoskeletal chest pain of
      cervicothoracic angina in patients with stable angina pectoris, based on patient
      history and clinical examination. Secondly, to examine the possibility of
      obtaining an objective diagnostic rule tool for the identification of
      cervicothoracic angina and to validate the diagnosis of this disorder. METHODS: A
      nonrandomized prospective trial was performed at a university hospital. A total
      of 516 of 972 consecutive patients referred for coronary angiography because of
      known or suspected angina pectoris were asked to participate in the study. Of
      these, 275 gave informed consent to a standardized manual examination of their
      spine and thorax. Diagnoses of an experienced chiropractor on cervicothoracic
      angina patients. Myocardial perfusion imaging and coronary angiography were used
      for validation. A set of candidate variables from patient history and clinical
      examination were tested for their role in the decision-making process. RESULTS:
      Eighteen percent of the patients were diagnosed with cervicothoracic angina. Of
      these, 80% had normal myocardial perfusion compared to 50% of cervicothoracic
      angina-negative patients. The main determinants of the decision-making process
      could be identified. CONCLUSION: An experienced chiropractor could identify a
      subset of patients with angina pectoris as having cervicothoracic angina.
      Systematic manual palpation of the spine and thorax could be used as part of the
      clinical examination together with basic cardiological variables to screen
      patients with chest pain allowing for improvements in referral patterns for
      specialist opinion or angiography.

PMID- 15965405
TI  - Does clinician treatment choice improve the outcomes of manual therapy for
      nonspecific low back pain? A metaanalysis.
AB  - OBJECTIVE: The purpose of this study is to quantitatively compare outcomes for
      trials when treating clinicians did, or did not, have the discretion to decide on
      treatment technique. METHODS: CINAHL, EMBASE, MEDLINE, the Physiotherapy Evidence
      Database, the Cochrane Controlled Trials register, reference list searching, and
      citation tracking were investigated. Ten randomized controlled trials (RCTs) of
      mobilization and manipulation for nonspecific low back pain (NSLBP) met the
      inclusion criteria. The effectiveness of manual therapy with and without
      clinician technique choice was assessed using descriptive statistics and
      metaanalysis for the outcomes of pain and activity limitation. RESULTS: In
      approximately two thirds of the included RCTs, clinicians had choice of treatment
      technique. There were no systematic differences favoring results for RCTs that
      did allow clinician choice of treatment technique. CONCLUSIONS: Few quality
      studies are available, and conclusions on the basis of these data need to be
      interpreted with caution. However, allowing clinicians to choose from a number of
      treatment techniques does not appear to have improved the outcomes of these RCTs
      that have investigated the effect of manual therapy for NSLBP. If tailoring
      manual therapy treatment to NSLBP patients does positively impact on patient
      outcomes, this is not yet systematically apparent.

PMID- 15965406
TI  - Posterior ponticles and rotational stenosis of vertebral arteries. A pilot study
      using Doppler ultrasound velocimetry and magnetic resonance angiography.
AB  - OBJECTIVE: To determine whether the presence of posterior ponticles markedly
      increases by 30% or more, the incidence of major rotational stenosis of vertebral
      arteries. METHODS: Doppler ultrasound studies were performed in 3 private
      chiropractic clinics and in the radiology department of a public hospital, and
      magnetic resonance angiography (MRA) studies were made in the latter location.
      Thirty-two chiropractic patients had Doppler velocimetery, and 16 of these
      patients had MRA scanning. The outcome measures included changes in Doppler
      velocimetry signals and MRA images indicative of marked rotational stenosis of
      vertebral arteries. RESULTS: All vertebral arteries from the 32 patients
      displayed no signs indicative of marked rotational stenosis. CONCLUSION: The
      findings of this study show that the incidence of major rotational stenosis of
      vertebral arteries is not markedly increased by the presence of posterior
      ponticles.

PMID- 15965407
TI  - An analysis of pubis symphysis misalignment using plain film radiography.
AB  - OBJECTIVE: To show, using a laboratory model, the inherent problems and test the
      validity of viewing actual pubis symphysis misalignment via plain film
      radiography in humans. STUDY DESIGN: In vitro experiment of pubic bone and pubis
      symphysis model alignment as determined through projected imaging with collimated
      light. RESULTS: The shadows cast by plastic models did not accurately reflect the
      physical reality. The image representations of the pubic bones with significant
      misalignment appeared as "normal." Some of the misalignments were viewed in the
      exact opposite alignment on the projected image as compared with the physical
      reality. CONCLUSIONS: This study provides evidence that misalignment of the pubic
      bones cannot be reliably viewed on a standard anteroposterior lumbopelvic
      radiograph. The results show the potential for missed diagnoses of clinical
      significance. Additional research on pelvic joint dysfunction and imaging
      problems is needed.

PMID- 15965408
TI  - Assessment of knowledge of primary care activities in a sample of medical and
      chiropractic students.
AB  - OBJECTIVE: To examine the influence of chiropractic education on knowledge of
      primary care tasks. Scores received on a test of knowledge of primary care tasks
      were compared between 3 samples of chiropractic students and 1 small sample of
      medical students. DATA SOURCES: The taxonomy of primary care tasks that was
      previously published provided the basis for test items used in this study. A team
      of test writers prepared an evaluation instrument that was administered to final
      term chiropractic students at 3 colleges and to a small sample of medical
      students as they were entering their residency programs. RESULTS: The
      chiropractic students scored below the medical students on the primary care
      examination in every area except musculoskeletal conditions. Chiropractic
      students scored higher than medical students on the musculoskeletal portion of
      the examination. CONCLUSIONS: In this sample, chiropractic students performed
      almost as well as medical students on a test that was designed to measure
      knowledge of primary care tasks. If the premise is accepted that medical school
      is the gold standard of primary care instruction, that chiropractic students
      fared almost as well as medical students is noteworthy.

PMID- 15965409
TI  - A review of compressive ulnar neuropathy at the elbow.
AB  - OBJECTIVE: To review the anatomy, etiology, and symptoms associated with
      compressive ulnar neuropathy at the elbow and to discuss the diagnosis and
      treatment of this condition. DATA SOURCE: The following were searched for
      information relevant to cubital tunnel syndrome: MEDLINE, WorldCat, and Index to
      Chiropractic Literature. RESULTS: Cubital tunnel syndrome is the second most
      common nerve compression syndrome of the upper extremity. Clinical features of
      this syndrome are described along with electrodiagnostic techniques that can be
      used to provide evidence concerning the probable location, character, and
      severity of the lesion affecting the ulnar nerve. Conservative treatment of
      cubital tunnel syndrome is recommended for patients with intermittent symptoms
      and without changes in cutaneous sensation or muscle atrophy. CONCLUSION: A
      definitive diagnosis can best be made using clinical tests along with nerve
      conduction studies and electromyography, conservative treatment can be effective
      in treating this neuropathy in mild cases; in moderate or severe cases, surgery
      may be necessary.

PMID- 15965410
TI  - A case of abnormal findings in the course of the vertebral artery associated with
      an ossified hyoid apparatus. A contraindication for manipulation of the cervical
      spine?
AB  - OBJECTIVE: To describe a case of a simultaneous occurrence of an ossified
      stylohyoid ligament in a 56-year-old male cadaver and anomalies of the vertebral
      artery, and to consider the clinical implications for manipulative therapists.
      INTERVENTION AND OUTCOME: Dissection showed a simultaneous occurrence of complete
      developmental ossification of the left hyoid apparatus, variants of the vertebral
      artery, and a left superior vena cava in a 56-year-old male cadaver. DISCUSSION:
      Developmental variants, posttraumatic and degenerative changes of the hyoid
      apparatus may result in variable degrees of ossification or calcification.
      CONCLUSION: This unusual disorder should be considered in the differential
      diagnosis of facial and neck pain especially within the scope of manipulation of
      the upper cervical spine. Cervical spine manipulation may exacerbate existing
      pathological conditions of the stylohyoid apparatus, thereby irritating
      neurovascular structures, and induce a fracture. Developmental ossification of
      this apparatus might be associated with anomalies in the atlantic section of the
      vertebral artery which make the patient more susceptible to vertebrobasilar
      insufficiency. We conclude that extreme care should be taken in the presence of
      such an ossification to avoid trauma to the stylohyoid apparatus and maybe even
      because of increased vertebrobasilar risk.

PMID- 15965411
TI  - A case report of manipulation under anesthesia of posttraumatic type II occipital
      atlantoaxial rotatory subluxation in a 4-year-old girl.
AB  - OBJECTIVE: To discuss a case of occipital-atlantoaxial rotatory subluxation
      successfully treated with manipulation under general anesthesia. CLINICAL
      FEATURES: A 4-year-old girl presented to the Taichung Veterans General Hospital
      with acute torticollis and neck stiffness for 1 week after she had fallen.
      Although some nonsteroidal anti-inflammatory drugs had been prescribed for her,
      her neck still tilted to the right side and her chin inclined to the left side.
      There were no neurological signs, no significant pain if she did not move her
      neck and head, and no muscular hypertonocity. There was painful guarding in the
      right sternocleidomatoid muscle when manipulation was attempted. Three
      dimensional computer tomography revealed uneven joint space between the C1
      anterior arch and odontoid process and confirmed a type II atlantoaxial rotatory
      subluxation. INTERVENTION AND OUTCOME: Manipulation under anesthesia was
      performed by a medical doctor trained in manual therapy. The low-velocity, right
      rotational manipulation applied to the occiput included axial traction. The neck
      symptoms were relieved immediately after treatment. CONCLUSION: Under general
      anesthesia, manipulation may be a good method for treating noncomplicated type II
      atlantoaxial rotatory subluxation. Additional investigations may be necessary to
      evaluate the treatment effect.

PMID- 15965412
TI  - Congestive heart failure: a review and case report from a chiropractic teaching
      clinic.
AB  - OBJECTIVE: To discuss the case of a 62-year-old woman with congestive heart
      failure (CHF), precipitated by a previous arteriovenous malformation, and to
      review the clinical presentation, pathophysiology, and treatment options for
      patients with CHF. CLINICAL FEATURES: The patient complained of pain, rapid
      weight gain, and shortness of breath. The index event for this patient was known
      to be an arteriovenous malformation. Biventricular cardiomegaly with pulmonary
      venous hypertension was evident on chest radiographs. INTERVENTION AND OUTCOME:
      The patient received both medical care (drug therapy) and chiropractic care
      (manipulation and soft tissue techniques to alleviate symptoms and discomfort).
      CONCLUSION: Patients with known and undiagnosed CHF may visit the chiropractic
      physician; thus, knowledge of comprehensive care, differential diagnosis, and
      continuity of care are important. Chiropractic management may be helpful in
      alleviating patient discomfort. Further clinical investigations may help to
      clarify the role of complementary and alternative care in the diagnosis and
      treatment of CHF.

PMID- 15965413
TI  - Invited commentary: self-reported nonmusculoskeletal responses to chiropractic
      intervention: a multination survey by Leboeuf-Yde et al.

PMID- 15965414
TI  - Chiropractic antivaccination arguments.

PMID- 15965415
TI  - The use of survival analysis for the evaluation of musculoskeletal therapy.

PMID- 15965417
TI  - Radiographic anomalies that may alter chiropractic intervention strategies found
      in a New Zealand population.

PMID- 15965418
TI  - Update on primary cicatricial alopecias.
AB  - The cicatricial alopecias encompass a diverse group of disorders characterized by
      permanent destruction of the hair follicle and irreversible hair loss.
      Destruction of the hair follicle can result from primary, folliculocentric
      disease or as a secondary result. This article focuses on the former, or primary
      cicatricial alopecias. The cause and pathogenesis of many of these disorders are
      largely unknown. Although unique clinicopathologic features allow for accurate
      diagnosis in some cases, diagnostic certainty is often elusive and reflects the
      limits of present understanding. Classification of the primary cicatricial
      alopecias on the basis of pathology provides a diagnostic and investigational
      framework and, it is hoped, will facilitate future enlightenment. Details of
      classification, etiopathogenesis, clinicopathologic features, differential
      diagnosis, and practical management of the primary cicatricial alopecias will be
      discussed. LEARNING OBJECTIVES: Upon completion of this learning activity,
      participants should be familiar with the following aspects of the primary
      cicatricial alopecias: (1) the new, consensus-issued classification scheme, (2)
      current understanding about etiopathogenesis, (3) salient clinicopathologic
      features, (4) differential diagnosis, and (5) therapeutic management.

PMID- 15965419
TI  - Consumers appropriately self-treat based on labeling for over-the-counter
      hydrocortisone.
AB  - BACKGROUND: Over-the-counter (OTC) topical corticosteroids, such as
      hydrocortisone cream (HC), are commonly used for the treatment of minor
      dermatological conditions. The safety and efficacy of such products are well
      documented, but details on patterns of use and self-treatment with HC in the OTC
      environment remain scarce. OBJECTIVE: We sought to determine compliance with
      label directions of OTC HCs by examining self-reported patterns of OTC HC use in
      adults and children. METHODS: A random digit-dialed telephone survey was
      conducted with 2000 US adults. Following identification of users of OTC HC in the
      last 6 months, respondents were asked questions about the conditions being
      treated with OTC HC and the frequency and duration of use in both adults and
      children. RESULTS: Of adults completing the survey, 20% (n = 396) had used OTC
      HC. In 83% of cases, the conditions treated were consistent with the OTC label.
      Use was limited; HC was applied < or =4 times daily in 98% of adult users and
      lasted < or =7 days in 92%. Patterns of pediatric use were similar and almost
      always consistent with the labeling. Of households with children, 25% (n = 168)
      had used OTC HC to treat pediatric dermatological conditions. Of child users, 93%
      were 2 years of age or older, treatment was limited (97% applied HC < or =4 times
      daily and 94% of treatments lasted < or =7 days), and the conditions treated were
      appropriate in 86% of cases. LIMITATIONS: This telephone survey relied on
      respondents' recall and self-reporting. Our data on pediatric use of OTC HC are
      skewed toward treatment of younger children. CONCLUSION: The data suggest that
      OTC HC products are used for self-treatment in a limited and appropriate fashion
      that is likely to be safe in both adults and children.

PMID- 15965420
TI  - Psoriasis herpeticum: three cases of Kaposi's varicelliform eruption in
      psoriasis.
AB  - BACKGROUND: Kaposi's varicelliform eruption (KVE), first described in 1887 by
      Moritz Kaposi, refers to a disseminated cutaneous infection with herpesvirus type
      1 or 2, vaccinia virus, or coxsackievirus A16 in a patient with another
      underlying dermatosis. When herpesvirus type 1 or 2 is the pathogenic virus, the
      term "eczema herpeticum" is used, independent of the underlying dermatologic
      diagnosis that preceded the eruption. KVE is most often seen in patients with
      underlying atopic dermatitis, but has also been seen in association with other
      papulosquamous and acantholytic disorders. However, eczema herpeticum rarely
      occurs in patients with psoriasis. OBSERVATIONS: We present the clinical and
      laboratory findings of three patients in whom KVE developed during inpatient
      hospitalization for a psoriatic flare. These patients each had comorbidities that
      may have increased susceptibility to KVE. CONCLUSIONS: KVE may rarely occur in
      patients with psoriasis. Erythroderma, systemic sepsis, therapy with
      immunosuppressant drugs, such as methotrexate and systemic steroids, and therapy
      with systemic retinoids may possibly increase susceptibility to KVE.

PMID- 15965421
TI  - Angiogenic cytokines in serum and cutaneous lesions of patients with
      polyarteritis nodosa.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) and vascular endothelial growth
      factor (VEGF) are angiogenic cytokines, that have been reported to elevate serum
      levels in patients with collagen diseases such as systemic sclerosis and
      dermatomyositis as well as in those with inflammatory bowel diseases. OBJECTIVE:
      In this study, the serum levels of bFGF and VEGF were measured by using enzyme
      linked immunosorbent assay in 20 patients with polyarteritis nodosa (PAN; 5 with
      systemic PAN and 15 with cutaneous PAN) and in 20 control subjects. We also
      investigated the expression of bFGF and VEGF in cutaneous lesions of patients by
      using immunohistochemical methods. RESULTS: Basic FGF was undetectable in the
      serum of control subjects, but detectable levels were found in 4 of 5 patients
      with classical PAN and 3 of 15 patients with cutaneous PAN. The serum bFGF level
      in these patients with systemic PAN was significantly elevated in comparison with
      that in healthy control subjects. The VEGF level was 178 +/- 41 pg/mL in the
      serum of healthy individuals. The mean VEGF level in patients with systemic or
      cutaneous PAN was significantly higher than that in healthy controls. Serum bFGF
      and VEGF levels in patients with systemic PAN were significantly elevated in
      comparison with those having cutaneous PAN. Immunohistochemical studies showed
      elevated bFGF expression on damaged endothelial cells in necrotizing vasculitis
      lesions. Elevated expression of bFGF was also observed on fibroblasts around the
      vasculitis. Some of the infiltrating cells around vasculitis lesions expressed
      VEGF. LIMITATIONS: The study was small. CONCLUSIONS: Serum bFGF and VEGF levels
      may be useful markers of the disease activities of PAN.

PMID- 15965422
TI  - Cutaneous necrosis after injection of polyethylene glycol-modified interferon
      alfa.
AB  - Pegylated interferon alfa-2b is a formulation of recombinant human interferon
      conjugated with polyethylene glycol. Compared with standard interferon alfa
      injections, this preparation has a longer half-life allowing for once-weekly
      injections and superior antiviral efficacy in the treatment of hepatitis C when
      used in combination with ribavirin. Cutaneous side effects caused by interferon
      are well known. Cutaneous necrosis as a result of interferon alfa is an
      infrequent complication with unknown pathogenesis, in which a cutaneous local
      immune-mediated inflammatory process might be involved. We report 5 patients (3
      patients with chronic hepatitis C treated with pegylated interferon alfa-2b in
      association with oral ribavirin and two patients with chronic myelocytic
      leukemia) who developed local cutaneous reactions at sites of injection after the
      administration of weekly subcutaneous injections of pegylated interferon alfa-2b
      at different doses. The ulcers slowly healed with local therapy, but two patients
      required dose modification of the pegylated interferon alfa-2b and one patient
      required treatment withdrawal. We review the literature on previously reported
      cases of cutaneous necrosis after injection of standard interferon alfa or
      pegylated interferon alfa-2b and discuss the different pathophysiologic
      mechanisms that might be involved.

PMID- 15965423
TI  - Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and
      erythroderma, and in healthy control subjects.
AB  - BACKGROUND: The aggravating role of Staphylococcus aureus superantigens is well
      known in atopic dermatitis (AD) but has not yet been proven in psoriasis (PS).
      OBJECTIVE: We investigated the distribution of S aureus in the skin and nares of
      patients with AD, PS vulgaris, erythroderma, skin infections, and sepsis, and in
      healthy control subjects. A Staphylococcal enterotoxin test-reversed passive
      latex agglutination (SET-RPLAR) test was performed to determine Staphylococcal
      enterotoxins A, B, C, and D. RESULTS: S aureus was cultivated from lesional skin
      of 22 of 25 patients with AD and 15 of 25 patients with PS. Isolated strains were
      toxigenic in 44% for patients with AD and in 36% for patients with PS. The
      activity of disease in AD and PS according to the Severity Scoring of Atopic
      Dermatitis (SCORAD) or Psoriasis Area and Severity Index score, respectively,
      correlated significantly (P = .001) with an isolated toxigenic strain in both
      diseases. S aureus from skin infections was toxigenic in half of the patients.
      All patients with erythroderma harbored S aureus, mostly on their skin. In AD,
      sepsis and skin infections, toxin C and in PS toxin B was most often detected. S
      aureus was cultured in 12% of healthy persons. These strains were toxin negative.
      The limitations of these investigations are that other potentially acting
      enterotoxins, such as toxic shock syndrome toxin-1, which may play a role in
      aggravating disease, were not investigated with our latex agglutination test.
      CONCLUSION: In this study, S aureus was present in more than 50% of patients with
      AD and PS. We found that the severity of AD and PS significantly correlated to
      enterotoxin production of the isolated S aureus strains.

PMID- 15965424
TI  - An extended 16-week course of alefacept in the treatment of chronic plaque
      psoriasis.
AB  - BACKGROUND: The efficacy and safety of one and two courses of alefacept have been
      demonstrated in phase 2 and 3 clinical trials, with a course of alefacept defined
      as 12 weeks of once-weekly treatment followed by 12 weeks of observation.
      METHODS: This randomized, single-center study compared the safety and efficacy of
      a standard 12-week versus extended 16-week alefacept dosing period in 20 patients
      with chronic plaque psoriasis. RESULTS: Both dose groups showed marked
      improvement in mean Psoriasis Area and Severity Index (PASI) score from baseline
      through week 24 (between-group difference: not significant). In each group, 60%
      of patients achieved PASI 50 (> or =50% reduction from baseline PASI score) at
      any time between weeks 12 and 24. For patients who received 16 weeks of
      alefacept, the mean percentage change from week-12 PASI score was higher and
      continued to increase through week 24 compared with that for patients who
      received 12 weeks of alefacept (P < .05). Adverse events were similar between the
      two groups and comparable with those observed in phase 2 and 3 clinical studies
      of alefacept. CONCLUSIONS: This was an open-label, single-center study of 20
      patients. Further study is warranted to assess the effect of alefacept when
      administered for more than 12 weeks. Extended dosing with alefacept appeared to
      have a similar safety profile to 12-week dosing and may offer further benefit to
      some patients for disease improvement.

PMID- 15965425
TI  - Childhood dermatofibrosarcoma protuberans: role of preoperative imaging.
AB  - Dermatofibrosarcoma protuberans (DFSP) is especially challenging to recognize and
      diagnose in children. Prompt and definitive treatment is essential based on the
      tumor's high rate of recurrence. Our purpose is to increase physician awareness
      and recognition of DFSP in the pediatric population with the largest case series
      of childhood DFSP to our knowledge thus reported in the literature. We also
      propose that magnetic resonance imaging (MRI) may be useful in the preoperative
      assessment. The records of 10 patients with primary DFSP between the ages of 8
      months and 16 years were reviewed. Only 1 of 10 patients was given the correct
      diagnosis at the initial medical evaluation. Of the 10 cases, 5 were congenital.
      The average delay in diagnosis was 5 years. Of the patients, 5 had preoperative
      MRI to delineate the size and extent of the tumor. In the two cases with the
      largest tumors preoperative MRI significantly altered surgical planning and
      execution. Thus, preoperative MRI may be helpful in planning for successful
      surgical clearance of large tumors and preventing local recurrence. All 10 cases
      were treated with Mohs micrographic surgery and no recurrences were noted with a
      follow-up range of 6 weeks to 17 years.

PMID- 15965427
TI  - Paradoxical hypertrichosis after laser epilation.
AB  - OBJECTIVE: Hair removal using lasers or broadband intense pulsed light has become
      one of the most ubiquitous medical procedures. At our center a small proportion
      of patients have spontaneously reported what they believed to be increased hair
      growth at sites of previous laser epilation. We sought to retrospectively review
      the prevalence and features of this paradoxical effect. METHODS: This was a
      single center, retrospective study that included all patients who underwent laser
      hair removal during a 4-year period with a long-pulsed alexandrite laser. All
      cases of laser-induced hypertrichosis were assessed clinically by history,
      examination, and laboratory tests, and confirmed by review of serial clinical
      photographs taken during the course of the laser treatments. The clinical
      features of patients with postlaser hypertrichosis were compared with 50 patients
      randomly selected from among all those who had undergone laser hair removal at
      our center (n = 489). RESULTS: Of 489 patients, 3 (0.6%, 95% confidence interval:
      0.01-1.9%) treated with the long-pulsed alexandrite laser (755 nm) reported
      increased hair after laser hair epilation. There was a trend for this adverse
      effect to occur in darker skin phototypes (IV) and with black hair as compared
      with the unaffected comparison group (n = 50). However, the small number of cases
      (n = 3) did not provide sufficient power to adequately test factors such as age,
      sex, treatment settings, and number of treatments statistically. CONCLUSION:
      Postlaser hair removal hypertrichosis is a real but rare occurrence in our
      experience.

PMID- 15965428
TI  - Completely regressed primary cutaneous malignant melanoma with nodal and/or
      visceral metastases: a report of 5 cases and assessment of the literature and
      diagnostic criteria.
AB  - BACKGROUND: Partial regression of primary cutaneous malignant melanoma is not
      uncommon and may predict a higher likelihood of metastasis and decreased
      survival. Complete histologic regression of a primary cutaneous melanoma is a
      rarer occurrence, with only 34 cases reported in the English-language or English
      language-summarized literature. OBSERVATION: We detail 4 cases of complete
      histologic regression of primary cutaneous melanoma, discovered at presentation
      with metastatic disease. A pigmented lesion or its remnant, coupled with
      historical information, was strongly suggestive of cutaneous melanoma. Histologic
      examination of the lesions, using multiple levels and immunohistochemical stains,
      failed to reveal residual melanoma. Our cases are typified by the presence of
      metastasis of melanoma to regional lymph nodes, with the absence of other suspect
      skin lesions or malignancies. In addition, we present a fifth case involving a
      completely regressed lesion on the scalp in a patient with cerebral melanoma
      metastasis and comment on the implications of this case to accepted diagnostic
      criteria, proposing that consideration of modification to the criteria be
      entertained. CONCLUSION: The concept of completely regressed primary cutaneous
      melanoma is reviewed and the literature critically appraised. When one considers
      a diagnosis of completely regressed primary cutaneous melanoma, cases must be
      well documented and biopsy proven. Patients with metastatic melanoma and an
      occult primary lesion require a thorough skin examination, with serious
      consideration given to the possibility of completely regressed cutaneous
      melanoma.

PMID- 15965429
TI  - Decision points for the initiation of systemic treatment for psoriasis.
AB  - Psoriasis has a tremendous effect on health-related quality of life. Phototherapy
      and systemic treatments are used for patients with more debilitating (physically
      and emotionally) forms of the disease. These treatments can be extremely
      effective but can also have potentially significant adverse effects. The decision
      to undertake systemic treatment of psoriasis is a complex one that requires both
      experience and judgment. With the recent advent of new biologic systemic drugs
      for moderate to severe psoriasis, the need to clarify patient candidates for
      systemic therapy has become very important. Here, we present a diagnostic
      algorithm and a formal measure, the Koo-Menter Psoriasis Instrument (KMPI), to
      aid in identifying patients that would benefit from systemic therapy. In
      addition, the KMPI can be used to document and justify treatment decisions for
      health care payers. While the decision to undertake systemic treatment and the
      choice of specific treatment plan must ultimately be made mutually by the patient
      and physician, these tools are designed to provide information that will be
      valuable in these determinations.

PMID- 15965430
TI  - B-RAF and melanocytic neoplasia.
AB  - High frequency of B-RAF gene mutations has recently been identified in benign
      melanocytic nevi and melanoma. This review focuses on clinical studies that
      evaluate the role of B-RAF in melanocytic neoplasia.

PMID- 15965431
TI  - Atopic dermatitis.

PMID- 15965433
TI  - Dermatology's malpractice experience: clinical settings for risk management.
AB  - BACKGROUND: Dermatologists need objective information that will help them make
      rational risk management decisions. OBJECTIVE: We asked, "What can be learned
      from the limited sources available regarding the clinical situations associated
      with malpractice litigation against dermatologists?" METHODS: We searched 2 legal
      databases, one jury verdict and settlement reporter, and reviewed and analyzed a
      major report from an association of physician insurers. RESULTS: A wide variety
      of clinical circumstances give rise to malpractice claims. Melanoma is still
      associated with high risk, and common conditions are associated with relative
      claim frequency. The clinical details currently available do not encourage
      optimal responses to reports of malpractice cases. CONCLUSION: Information that
      clinicians can use in their own risk management efforts can be derived from
      available sources, but more reliable objective data is needed.

PMID- 15965432
TI  - Head lice: scientific assessment of the nit sheath with clinical ramifications
      and therapeutic options.
AB  - Head lice, like many insects, produce a protective coating for their newly laid
      eggs that is essential to the survival of the species. Knowledge of the
      composition of the sheath, which is the glue by which the egg is attached to
      human hair, and the nit laying process could lead to production of agents that
      could be used to attack louse infestations by interfering with the normally
      protected environment of nymph development within the egg. The physical removal
      of nits has become an important part of treatment of head louse infestations
      given the "no-nit" policy in schools. Biochemical analysis has revealed that the
      nit sheath of the head louse is composed of 4 bands of protein, possibly cross
      linked to aliphatic components with a tertiary structure of beta sheeting. Nature
      has protected the louse by making the nit sheath similar in composition to the
      hair; thereby, agents designed to unravel the nit sheath may also damage human
      hair. Possible targets to destroy the nit sheath include proteases, denaturants,
      beta sheet breaker proteins, and small protein inhibitors of sheath formation.
      Better understanding of insect glues may allow us to develop compounds so that
      the liquid secretions of the collateral glands of the female louse, which becomes
      the nit sheath, do not solidify by oxidation when placed with the louse egg onto
      human hair. Knowledge of insect behavior, such as oviposition, may also suggest
      methods for repelling female lice from laying eggs onto hair. Alternatively,
      agents that coat the nits and restrict the oxygen transfer to the developing
      larvae may prove beneficial.

PMID- 15965434
TI  - Cutaneous signs of child abuse.

PMID- 15965435
TI  - Health insurance benefit limits: general concepts and the potential impact on
      dermatologic treatment.

PMID- 15965436
TI  - Surgical pearl: artificial skin model for simulation of flap mechanics.

PMID- 15965437
TI  - Surgical pearl: the "fishhook" needle technique: a solution to the large needle,
      small space dilemma.

PMID- 15965438
TI  - Montelukast treatment of moderate to severe atopic dermatitis in adults: a
      randomized, double-blind, placebo-controlled trial.
AB  - In a randomized, double-blind, placebo-controlled 4-week trial, 59 patients with
      moderate to severe atopic dermatitis were treated orally with 10 mg of the
      leukotriene antagonist montelukast. Forty-seven patients completed the study. No
      difference in efficacy was seen among patients who received montelukast and the
      group given a placebo.

PMID- 15965439
TI  - Treatment of uremic pruritus with narrowband ultraviolet B phototherapy: an open
      pilot study.
AB  - We report the results of a pilot study of narrowband ultraviolet B phototherapy
      for the treatment of 20 patients with uremic pruritus. Ten patients completed the
      6-week study period. A total of 8 patients were found to be responders. Of the
      remaining 10 patients who left the study before 6 weeks, 6 were satisfied with
      the response. In the follow-up period, 7 responders could be examined, and 3 were
      in remission 6 months after completing treatment. However, pruritus recurred in
      the remaining 4 responders. Narrowband ultraviolet B phototherapy may be an
      effective treatment for patients with uremic pruritus. Recurrence of pruritus,
      however, is a frequent problem.

PMID- 15965440
TI  - T-cell clonality of peripheral blood lymphocytes in patients with lymphomatoid
      papulosis.
AB  - Six patients with lymphomatoid papulosis demonstrated a clonal T-cell population
      in skin lesions by polymerase chain reaction methods. Two of these patients
      showed identical T-cell clones in their peripheral blood T cells as well. In one
      case, the clone persisted in the blood despite clearing of skin lesions with
      methotrexate.

PMID- 15965441
TI  - Progression of classic Kaposi's sarcoma with rituximab.
AB  - Rituximab is a monoclonal antibody directed against the CD20 antigen of B cells
      and is being used increasingly for treatment of antibody-mediated autoimmune
      diseases. We observed the rapid progression of Kaposi's sarcoma after our patient
      received rituximab for autoimmune hemolytic anemia. We postulate that by very
      specifically depleting B cells, rituximab affects T-cell function (eliminating B-
      and T-cell interactions), resulting in impaired T-cell-mediated immunity.
      Dermatologists should use caution when offering rituximab for off-label use.

PMID- 15965442
TI  - Mycosis fungoides with a CD56+ immunophenotype.
AB  - We report 3 cases of mycosis fungoides (MF) with a CD56+ cytotoxic
      immunophenotype. Each patient presented with a different clinical phenotype: one
      exhibited limited poikilodermatous patches (skin stage T1); one, widespread
      hypopigmented lesions (skin stage T2); and one, poikiloderma with a single
      cutaneous tumor (skin stage T3). MF was confirmed both histologically and by the
      presence of a T-cell receptor clone in lesional skin in all cases. CD56 and T
      cell intracellular antigen-1 were expressed by the malignant lymphocytes in all
      patients and two expressed CD8. No sample demonstrated loss of the pan T-cell
      markers CD2 or CD3. None of the 3 developed systemic disease and T-cell receptor
      gene analysis of peripheral blood was polyclonal in all cases. Only 3 cases of
      CD56+ MF have been reported previously, none of which exhibited tumor-stage
      disease. Currently, the disease in our patients appears to be behaving in a
      manner similar to that predicted for MF with a normal immunophenotype but the
      prognosis has to be guarded in view of the rarity of this subtype.

PMID- 15965443
TI  - Nit picking.

PMID- 15965444
TI  - Pigmented purpuric dermatosis (capillaritis) induced by bezafibrate.

PMID- 15965445
TI  - Pseudoporhyria secondary to acitretin.

PMID- 15965446
TI  - Photopheresis does not improve survival in Sezary syndrome patients with bone
      marrow involvement.

PMID- 15965447
TI  - Negative results of patch testing with standard and textile series in a case of
      annular lichenoid dermatitis of youth.

PMID- 15965448
TI  - Resolution of acne following therapy with an oral contraceptive in a patient with
      Apert syndrome.

PMID- 15965449
TI  - Generalized elastolysis following nephrogenic fibrosing dermopathy.

PMID- 15965450
TI  - Scleroderma-like changes in cutaneous eruption of rhabdomyolysis.

PMID- 15965451
TI  - Neutrophilic fixed drug eruption caused by naproxen: a real entity or a stage in
      the histopathologic evolution of the disease?

PMID- 15965452
TI  - Cutaneous metaplastic synovial cyst.

PMID- 15965453
TI  - Isotretinoin does have an adverse effect on bone mineral density.

PMID- 15965454
TI  - Eosinophilia: outcomes and bias.

PMID- 15965463
TI  - Microstructure of a spatial map in the entorhinal cortex.
AB  - The ability to find one's way depends on neural algorithms that integrate
      information about place, distance and direction, but the implementation of these
      operations in cortical microcircuits is poorly understood. Here we show that the
      dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented,
      topographically organized neural map of the spatial environment. Its key unit is
      the 'grid cell', which is activated whenever the animal's position coincides with
      any vertex of a regular grid of equilateral triangles spanning the surface of the
      environment. Grids of neighbouring cells share a common orientation and spacing,
      but their vertex locations (their phases) differ. The spacing and size of
      individual fields increase from dorsal to ventral dMEC. The map is anchored to
      external landmarks, but persists in their absence, suggesting that grid cells may
      be part of a generalized, path-integration-based map of the spatial environment.

PMID- 15965464
TI  - RNA-interference-directed chromatin modification coupled to RNA polymerase II
      transcription.
AB  - RNA interference (RNAi) acts on long double-stranded RNAs (dsRNAs) in a variety
      of eukaryotes to generate small interfering RNAs that target homologous messenger
      RNA, resulting in their destruction. This process is widely used to 'knock-down'
      the expression of genes of interest to explore phenotypes. In plants, fission
      yeast, ciliates, flies and mammalian cells, short interfering RNAs (siRNAs) also
      induce DNA or chromatin modifications at the homologous genomic locus, which can
      result in transcriptional silencing or sequence elimination. siRNAs may direct
      DNA or chromatin modification by siRNA-DNA interactions at the homologous locus.
      Alternatively, they may act by interactions between siRNA and nascent transcript.
      Here we show that in fission yeast (Schizosaccharomyces pombe), chromatin
      modifications are only directed by RNAi if the homologous DNA sequences are
      transcribed. Furthermore, transcription by exogenous T7 polymerase is not
      sufficient. Ago1, a component of the RNAi effector RISC/RITS complex, associates
      with target transcripts and RNA polymerase II. Truncation of the regulatory
      carboxy-terminal domain (CTD) of RNA pol II disrupts transcriptional silencing,
      indicating that, like other RNA processing events, RNAi-directed chromatin
      modification is coupled to transcription.

PMID- 15965465
TI  - Engineering vascularized skeletal muscle tissue.
AB  - One of the major obstacles in engineering thick, complex tissues such as muscle
      is the need to vascularize the tissue in vitro. Vascularization in vitro could
      maintain cell viability during tissue growth, induce structural organization and
      promote vascularization upon implantation. Here we describe the induction of
      endothelial vessel networks in engineered skeletal muscle tissue constructs using
      a three-dimensional multiculture system consisting of myoblasts, embryonic
      fibroblasts and endothelial cells coseeded on highly porous, biodegradable
      polymer scaffolds. Analysis of the conditions for induction and stabilization of
      the vessels in vitro showed that addition of embryonic fibroblasts increased the
      levels of vascular endothelial growth factor expression in the construct and
      promoted formation and stabilization of the endothelial vessels. We studied the
      survival and vascularization of the engineered muscle implants in vivo in three
      different models. Prevascularization improved the vascularization, blood
      perfusion and survival of the muscle tissue constructs after transplantation.

PMID- 15965466
TI  - Telomere fusion to chromosome breaks reduces oncogenic translocations and tumour
      formation.
AB  - Telomeres protect chromosome ends from fusion, degradation and recombination.
      Loss of telomere function has opposite effects on tumorigenesis: apoptosis, which
      inhibits tumour growth, and genomic instability, which accelerates tumour
      formation. Here we describe a new mechanism by which short telomeres inhibit
      tumorigenesis through interference with oncogenic translocations. In mice that
      are null for both ataxia-telangiectasia-mutated (Atm) and telomerase RNA (mTR),
      the first generation (G1) Atm-/- mTR-/- mice have a lower rate of tumour
      formation than Atm-/- mTR+/+ mice. These Atm-/- mTR-/- G1 tumours show no
      increase in either apoptosis or overall genomic instability. Strikingly, the
      tumours show a high fraction of translocations containing telomere signals at the
      translocation junctions. Translocations of the T-cell receptors on chromosome 14,
      which initiate tumorigenesis, were interrupted by fusion with telomeres. Telomere
      repeats were also detected at the translocation junctions in pre-malignant
      thymocytes. We propose that telomere fusion to DNA double-strand breaks competes
      with the generation of oncogenic translocations and thus reduces tumour
      formation.

PMID- 15965467
TI  - NudEL targets dynein to microtubule ends through LIS1.
AB  - Dynein is a minus-end-directed microtubule motor with critical roles in mitosis,
      membrane transport and intracellular transport. Several proteins regulate dynein
      activity, including dynactin, LIS1 (refs 2, 3) and NudEL (NudE-like). Here, we
      identify a NUDEL homologue in budding yeast and name it Ndl1. The ndl1delta null
      mutant shows decreased targeting of dynein to microtubule plus ends, an essential
      element of the model for dynein function. We find that Ndl1 regulates dynein
      targeting through LIS1, with which it interacts biochemically, but not through
      CLIP170, another plus-end protein involved in dynein targeting. Ndl1 is found at
      far fewer microtubule ends than are LIS1 and dynein. However, when Ndl1 is
      present at a plus end, the molar amount of Ndl1 approaches that of LIS1 and
      dynein. We propose a model in which Ndl1 binds transiently to the plus end to
      promote targeting of LIS1, which cooperatively recruits dynein.

PMID- 15965468
TI  - The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone
      activation and PTHrP secretion in the developing growth plate.
AB  - WSB-1 is a SOCS-box-containing WD-40 protein of unknown function that is induced
      by Hedgehog signalling in embryonic structures during chicken development. Here
      we show that WSB-1 is part of an E3 ubiquitin ligase for the thyroid-hormone
      activating type 2 iodothyronine deiodinase (D2). The WD-40 propeller of WSB-1
      recognizes an 18-amino-acid loop in D2 that confers metabolic instability,
      whereas the SOCS-box domain mediates its interaction with a ubiquitinating
      catalytic core complex, modelled as Elongin BC-Cul5-Rbx1 (ECS(WSB-1)). In the
      developing tibial growth plate, Hedgehog-stimulated D2 ubiquitination via ECS(WSB
      1) induces parathyroid hormone-related peptide (PTHrP), thereby regulating
      chondrocyte differentiation. Thus, ECS(WSB-1) mediates a mechanism by which
      'systemic' thyroid hormone can effect local control of the Hedgehog-PTHrP
      negative feedback loop and thus skeletogenesis.

PMID- 15965469
TI  - Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse
      models.
AB  - Nijmegen breakage syndrome (NBS) is a chromosomal fragility disorder that shares
      clinical and cellular features with ataxia telangiectasia. Here we demonstrate
      that Nbs1-null B cells are defective in the activation of ataxia-telangiectasia
      mutated (Atm) in response to ionizing radiation, whereas ataxia-telangiectasia-
      and Rad3-related (Atr)-dependent signalling and Atm activation in response to
      ultraviolet light, inhibitors of DNA replication, or hypotonic stress are intact.
      Expression of the main human NBS allele rescues the lethality of Nbs1-/- mice,
      but leads to immunodeficiency, cancer predisposition, a defect in meiotic
      progression in females and cell-cycle checkpoint defects that are associated with
      a partial reduction in Atm activity. The Mre11 interaction domain of Nbs1 is
      essential for viability, whereas the Forkhead-associated (FHA) domain is required
      for T-cell and oocyte development and efficient DNA damage signalling.
      Reconstitution of Nbs1 knockout mice with various mutant isoforms demonstrates
      the biological impact of impaired Nbs1 function at the cellular and organismal
      level.

PMID- 15965470
TI  - DNER acts as a neuron-specific Notch ligand during Bergmann glial development.
AB  - Differentiation of CNS glia is regulated by Notch signaling through neuron-glia
      interaction. Here, we identified Delta/Notch-like EGF-related receptor (DNER), a
      neuron-specific transmembrane protein, as a previously unknown ligand of Notch
      during cellular morphogenesis of Bergmann glia in the mouse cerebellum. DNER
      binds to Notch1 at cell-cell contacts and activates Notch signaling in vitro. In
      the developing cerebellum, DNER is highly expressed in Purkinje cell dendrites,
      which are tightly associated with radial fibers of Bergmann glia expressing
      Notch. DNER specifically binds to Bergmann glia in culture and induces process
      extension by activating gamma-secretase- and Deltex-dependent Notch signaling.
      Inhibition of Deltex-dependent, but not RBP-J-dependent, Notch signaling in
      Bergmann glia suppresses formation and maturation of radial fibers in organotypic
      slice cultures. Additionally, deficiency of DNER retards the formation of radial
      fibers and results in abnormal arrangement of Bergmann glia. Thus, DNER mediates
      neuron-glia interaction and promotes morphological differentiation of Bergmann
      glia through Deltex-dependent Notch signaling.

PMID- 15965471
TI  - Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine.
AB  - Caffeine, a component of tea, coffee and cola, induces wakefulness. It binds to
      adenosine A1 and A2A receptors as an antagonist, but the receptor subtype
      mediating caffeine-induced wakefulness remains unclear. Here we report that
      caffeine at 5, 10 and 15 mg kg(-1) increased wakefulness in both wild-type mice
      and A1 receptor knockout mice, but not in A2A receptor knockout mice. Thus,
      caffeine-induced wakefulness depends on adenosine A2A receptors.

PMID- 15965472
TI  - Saccadic eye movements cause compression of time as well as space.
AB  - There is now considerable evidence that space is compressed when stimuli are
      flashed shortly before or after the onset of a saccadic eye movement. Here we
      report that short intervals of time between two successive perisaccadic visual
      (but not auditory) stimuli are also underestimated, indicating a compression of
      perceived time. We were even more surprised that in a critical interval before
      saccades, perceived temporal order is consistently reversed. The very similar
      time courses of spatial and temporal compression suggest that both are mediated
      by a common neural mechanism, probably related to the predictive shifts that
      occur in receptive fields of many visual areas at the time of saccades.

PMID- 15965473
TI  - GRIP1 controls dendrite morphogenesis by regulating EphB receptor trafficking.
AB  - The function of the multi-PDZ domain scaffold protein GRIP1 (glutamate receptor
      interacting protein 1) in neurons is unclear. To explore the function of GRIP1 in
      hippocampal neurons, we used RNA interference (RNAi) to knock down the expression
      of GRIP1. Knockdown of GRIP1 by small interfering RNA (siRNA) in cultured
      hippocampal neurons caused a loss of dendrites, associated with mislocalization
      of the GRIP-interacting proteins GIuR2 (AMPA receptor subunit), EphB2 (receptor
      tyrosine kinase) and KIF5 (also known as kinesin 1; microtubule motor). The loss
      of dendrites by GRIP1-siRNA was rescued by overexpression of the extracellular
      domain of EphB2, and was phenocopied by overexpression of the intracellular
      domain of EphB2 and extracellular application of ephrinB-Fc fusion proteins.
      Neurons from EphB1-EphB2-EphB3 triple knockout mice showed abnormal dendrite
      morphogenesis. Disruption of the KIF5-GRIP1 interaction inhibited EphB2
      trafficking and strongly impaired dendritic growth. These results indicate an
      important role for GRIP1 in dendrite morphogenesis by serving as an adaptor
      protein for kinesin-dependent transport of EphB receptors to dendrites.

PMID- 15965474
TI  - Identification of hundreds of conserved and nonconserved human microRNAs.
AB  - MicroRNAs are noncoding RNAs of approximately 22 nucleotides that suppress
      translation of target genes by binding to their mRNA and thus have a central role
      in gene regulation in health and disease. To date, 222 human microRNAs have been
      identified, 86 by random cloning and sequencing, 43 by computational approaches
      and the rest as putative microRNAs homologous to microRNAs in other species. To
      prove our hypothesis that the total number of microRNAs may be much larger and
      that several have emerged only in primates, we developed an integrative approach
      combining bioinformatic predictions with microarray analysis and sequence
      directed cloning. Here we report the use of this approach to clone and sequence
      89 new human microRNAs (nearly doubling the current number of sequenced human
      microRNAs), 53 of which are not conserved beyond primates. These findings suggest
      that the total number of human microRNAs is at least 800.

PMID- 15965475
TI  - An integrative genomics approach to infer causal associations between gene
      expression and disease.
AB  - A key goal of biomedical research is to elucidate the complex network of gene
      interactions underlying complex traits such as common human diseases. Here we
      detail a multistep procedure for identifying potential key drivers of complex
      traits that integrates DNA-variation and gene-expression data with other complex
      trait data in segregating mouse populations. Ordering gene expression traits
      relative to one another and relative to other complex traits is achieved by
      systematically testing whether variations in DNA that lead to variations in
      relative transcript abundances statistically support an independent, causative or
      reactive function relative to the complex traits under consideration. We show
      that this approach can predict transcriptional responses to single gene
      perturbation experiments using gene-expression data in the context of a
      segregating mouse population. We also demonstrate the utility of this approach by
      identifying and experimentally validating the involvement of three new genes in
      susceptibility to obesity.

PMID- 15965476
TI  - Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal
      instability and cancer in mice.
AB  - Most cancers have multiple chromosomal rearrangements; the molecular mechanisms
      that generate them remain largely unknown. Mice carrying a heterozygous missense
      change in one of the DNA-binding domains of Rpa1 develop lymphoid tumors, and
      their homozygous littermates succumb to early embryonic lethality. Array
      comparative genomic hybridization of the tumors identified large-scale
      chromosomal changes as well as segmental gains and losses. The Rpa1 mutation
      resulted in defects in DNA double-strand break repair and precipitated
      chromosomal breaks as well as aneuploidy in primary heterozygous mutant mouse
      embryonic fibroblasts. The equivalent mutation in yeast is hypomorphic and
      semidominant and enhanced the formation of gross chromosomal rearrangements in
      multiple genetic backgrounds. These results indicate that Rpa1 functions in DNA
      metabolism are essential for the maintenance of chromosomal stability and tumor
      suppression.

PMID- 15965477
TI  - Trans-dominant inhibition of RNA viral replication can slow growth of drug
      resistant viruses.
AB  - The high error rates of viral RNA-dependent RNA polymerases create heterogeneous
      viral populations whose disparate RNA genomes affect each other's survival. We
      systematically screened the poliovirus genome and identified four sets of
      dominant mutations. Mutated alleles in capsid- and polymerase-coding regions
      resulted in dominant negative phenotypes, probably due to the proteins'
      oligomeric properties. We also identified dominant mutations in an RNA element
      required for priming RNA synthesis (CRE) and in the protein primer (VPg),
      suggesting that nonproductive priming intermediates are inhibitory. Mutations
      that inhibit the activity of viral proteinase 2A were dominant, arguing that
      inhibition of its known intramolecular activity creates a toxic product. Viral
      products that, when defective, dominantly interfere with growth of nondefective
      viruses will probably be excellent drug targets because drug-sensitive viruses
      should be dominant over drug-resistant variants. Accordingly, a virus sensitive
      to anticapsid compound WIN51711 dominantly inhibited the intracellular growth of
      a drug-resistant virus. Therefore, dominant inhibitor screening should validate
      or predict targets for antiviral therapy with reduced risk for drug resistance.

PMID- 15965478
TI  - A modular and supramolecular approach to bioactive scaffolds for tissue
      engineering.
AB  - Bioactive polymeric scaffolds are a prerequisite for the ultimate formation of
      functional tissues. Here, we show that supramolecular polymers based on quadruple
      hydrogen bonding ureido-pyrimidinone (UPy) moieties are eminently suitable for
      producing such bioactive materials owing to their low-temperature processability,
      favourable degradation and biocompatible behaviour. Particularly, the reversible
      nature of the hydrogen bonds allows for a modular approach to gaining control
      over cellular behaviour and activity both in vitro and in vivo. Bioactive
      materials are obtained by simply mixing UPy-functionalized polymers with UPy
      modified biomolecules. Low-molecular-weight bis-UPy-oligocaprolactones with cell
      adhesion promoting UPy-Gly-Arg-Gly-Asp-Ser (UPy-GRGDS) and the synergistic UPy
      Pro-His-Ser-Arg-Asn (UPy-PHSRN) peptide sequences are synthesized and studied.
      The in vitro results indicate strong and specific cell binding of fibroblasts to
      the UPy-functionalized bioactive materials containing both UPy-peptides. An even
      more striking effect is seen in vivo where the formation of single giant cells at
      the interface between bioactive material and tissue is triggered.

PMID- 15965479
TI  - Tuning the conductance of single-walled carbon nanotubes by ion irradiation in
      the Anderson localization regime.
AB  - Carbon nanotubes are a good realization of one-dimensional crystals where basic
      science and potential nanodevice applications merge. Defects are known to modify
      the electrical resistance of carbon nanotubes; they can be present in as-grown
      carbon nanotubes, but controlling their density externally opens a path towards
      the tuning of the electronic characteristics of the nanotube. In this work,
      consecutive Ar+ irradiation doses are applied to single-walled nanotubes (SWNTs)
      producing a uniform density of defects. After each dose, the room-temperature
      resistance versus SWNT length (R(L)) along the nanotube is measured. Our data
      show an exponential dependence of R(L) indicating that the system is within the
      strong Anderson localization regime. Theoretical simulations demonstrate that
      mainly di-vacancies contribute to the resistance increase induced by irradiation,
      and that just a 0.03% of di-vacancies produces an increase of three orders of
      magnitude in the resistance of a SWNT of 400 nm length.

PMID- 15965480
TI  - All-optical control of microfluidic components using form birefringence.
AB  - The reflection and refraction of light at a dielectric interface gives rise to
      forces due to changes in the photon momentum. At the microscopic level, these
      forces are sufficient to trap and rotate microscopic objects. Such forces may
      have a profound impact in the emergent area of microfluidics, where there is the
      desire to process minimal amounts of analyte. This places stringent criteria on
      the ability to pump, move and mix small volumes of fluid, which will require the
      use of micro-components and their controlled actuation. We demonstrate the
      modelling, fabrication and rotation of microgears based on the principle of form
      birefringence. Using a geometric anisotropy (a one-dimensional photonic crystal
      etched into the microgear), we can fabricate microgears of known birefringence,
      which may be readily rotated by manipulating the input polarization in a standard
      optical trap. This methodology offers a new and powerful mechanism for generating
      a wide range of microfabricated machines, such as micropumps, that may be driven
      by purely optical control.

PMID- 15965481
TI  - Rewritable phosphorescent paper by the control of competing kinetic and
      thermodynamic self-assembling events.
AB  - Security inks have become of increasing importance. They are composed of
      invisible substances that provide printed images that are not able to be
      photocopied, and are readable only under special environments. Here we report a
      novel photoluminescent ink for rewritable media that dichroically emits
      phosphorescence due to a structural bistability of the self-assembled luminophor.
      Long-lasting images have been developed by using conventional thermal printers,
      which are readable only on exposure to ultraviolet light, and more importantly,
      are thermally erasable for rewriting. Although thermally rewritable printing
      media have already been developed using visible dyes and cholesteric liquid
      crystals, security inks that allow rewriting of invisible printed images are
      unprecedented. We realized this unique feature by the control of kinetic and
      thermodynamic processes that compete with one another in the self-assembly of the
      luminophor. This strategy can provide an important step towards the next
      generation security technology for information handling.

PMID- 15965482
TI  - A rapid and potent DNA vaccination strategy defined by in vivo monitoring of
      antigen expression.
AB  - Induction of immunity after DNA vaccination is generally considered a slow
      process. Here we show that DNA delivery to the skin results in a highly transient
      pulse of antigen expression. Based on this information, we developed a new rapid
      and potent intradermal DNA vaccination method. By short-interval intradermal DNA
      delivery, robust T-cell responses, of a magnitude sufficient to reject
      established subcutaneous tumors, are generated within 12 d. Moreover, this
      vaccination strategy confers protecting humoral immunity against influenza A
      infection within 2 weeks after the start of vaccination. The strength and speed
      of this newly developed strategy will be beneficial in situations in which
      immunity is required in the shortest possible time.

PMID- 15965483
TI  - Fat apoptosis through targeted activation of caspase 8: a new mouse model of
      inducible and reversible lipoatrophy.
AB  - We describe the generation and characterization of the first inducible 'fatless'
      model system, the FAT-ATTAC mouse (fat apoptosis through targeted activation of
      caspase 8). This transgenic mouse develops identically to wild-type littermates.
      Apoptosis of adipocytes can be induced at any developmental stage by
      administration of a FK1012 analog leading to the dimerization of a membrane
      bound, adipocyte-specific caspase 8-FKBP fusion protein. Within 2 weeks of
      dimerizer administration, FAT-ATTAC mice show near-knockout levels of circulating
      adipokines and markedly reduced levels of adipose tissue. FAT-ATTAC mice are
      glucose intolerant, have diminished basal and endotoxin-stimulated systemic
      inflammation, are less responsive to glucose-stimulated insulin secretion and
      show increased food intake independent of the effects of leptin. Most
      importantly, we show that functional adipocytes can be recovered upon cessation
      of treatment, allowing the study of adipogenesis in vivo, as well as a detailed
      examination of the importance of the adipocyte in the regulation of multiple
      physiological functions and pathological states.

PMID- 15965484
TI  - Splicing regulates NAD metabolite binding to histone macroH2A.
AB  - Histone macroH2A is a hallmark of mammalian heterochromatin. Here we show that
      human macroH2A1.1 binds the SirT1-metabolite O-acetyl-ADP-ribose (OAADPR) through
      its macro domain. The 1.6-A crystal structure and mutants reveal how the
      metabolite is recognized. Mutually exclusive exon use in the gene H2AFY produces
      macroH2A1.2, whose tissue distribution differs. MacroH2A1.2 shows only subtle
      structural changes but cannot bind nucleotides. Alternative splicing may thus
      regulate the binding of nicotinamide adenine dinucleotide (NAD) metabolites to
      chromatin.

PMID- 15965485
TI  - Cryo-electron microscopy reconstruction of a poliovirus-receptor-membrane
      complex.
AB  - To study non-enveloped virus cell entry, a versatile in vitro model system was
      developed in which liposomes containing nickel-chelating lipids were decorated
      with His-tagged poliovirus receptors and bound to virus. This system provides an
      exciting opportunity for structural characterization of the early steps in cell
      entry in the context of a membrane. Here we report the three-dimensional
      structure of a poliovirus-receptor-membrane complex solved by cryo-electron
      microscopy (cryo-EM) at a resolution of 32 A. Methods were developed to establish
      the symmetry of the complex objectively. This reconstruction demonstrates that
      receptor binding brings a viral five-fold axis close to the membrane. Density is
      clearly defined for the icosahedral virus, for receptors (including known
      glycosylation sites) and for the membrane bilayer. Apparent perturbations of the
      bilayer close to the viral five-fold axis may function in subsequent steps of
      cell entry.

PMID- 15965486
TI  - Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for
      retromer assembly.
AB  - The retromer complex is responsible for the retrieval of mannose 6-phosphate
      receptors from the endosomal system to the Golgi. Here we present the crystal
      structure of the mammalian retromer subunit mVps29 and show that it has
      structural similarity to divalent metal-containing phosphoesterases. mVps29 can
      coordinate metals in a similar manner but has no detectable phosphoesterase
      activity in vitro, suggesting a unique specificity or function. The mVps29 and
      mVps26 subunits bind independently to mVps35 and together form a high-affinity
      heterotrimeric subcomplex. Mutagenesis reveals the structural basis for the
      interaction of mVps29 with mVps35 and subsequent association with endosomal
      membranes in vivo. A conserved hydrophobic surface distinct from the primary
      Vps35p binding site mediates assembly of the Vps29p-Vps26p-Vps35p subcomplex with
      sorting nexins in yeast, and mutation of either site results in a defect in
      retromer-dependent membrane trafficking.

PMID- 15965487
TI  - BRCA1 participates in DNA decatenation.
AB  - The tumor suppressor BRCA1 has an important function in the maintenance of
      genomic stability. Increasing evidence suggests that BRCA1 regulates cell cycle
      checkpoints and DNA repair after DNA damage. However, little is known about its
      normal function in the absence of DNA damage. Here we show that BRCA1 interacts
      and colocalizes with topoisomerase IIalpha in S phase cells. Similar to cells
      treated with the topoisomerase IIalpha inhibitor ICRF-193, BRCA1-deficient cells
      show lagging chromosomes, indicating a defect in DNA decatenation and chromosome
      segregation. More directly, BRCA1 deficiency results in defective DNA
      decatenation in vitro. Finally, topoisomerase IIalpha is ubiquitinated in a BRCA1
      dependent manner, and topoisomerase IIalpha ubiquitination correlates with higher
      DNA decatenation activity. Together these results suggest an important role of
      BRCA1 in DNA decatenation and reveal a previously unknown function of BRCA1 in
      the maintenance of genomic stability.

PMID- 15965488
TI  - Establishment of a benign meningioma cell line by hTERT-mediated immortalization.
AB  - Meningioma represents the most common intracranial tumor, but well-characterized
      cell lines derived from benign meningiomas are not available. A major reason for
      the lack of benign tumor cell lines is senescence of nonmalignant cells in vitro,
      while malignant cells are often immortal. We have developed a meningioma cell
      line by retrovirally transducing primary cells derived from a human WHO grade I
      meningothelial meningioma with the human telomerase reverse transcriptase (hTERT)
      gene, which enables bypassing cellular senescence. Five clones have been cultured
      for more than 21 months so far, while corresponding nontransfected cells ceased
      proliferation within 3 months. Quantitative RT-PCR and a telomeric repeat
      amplification protocol (TRAP) assay revealed high hTERT mRNA levels and high
      telomerase activity in all transduced populations, while nontransduced cells were
      negative. The average telomere size of transduced cells was considerably longer
      than that of parental cells and the biopsy specimen. One clone, designated Ben
      Men-1, was characterized in more detail, and exhibited typical cytological,
      immunocytochemical, ultrastructural and genetical features of meningioma,
      including whorl formation, expression of epithelial membrane antigen, desmosomes
      and interdigitating cell processes, as well as -22q. Following subdural
      transplantation into nude mice, tumor tissue with typical histological features
      of meningothelial meningioma was found. We conclude that Ben-Men-1 represents an
      immortalized yet differentiated cell line useful for biological and therapeutical
      studies on meningioma.

PMID- 15965489
TI  - Helicobacter felis-induced gastritis was suppressed in mice overexpressing
      thioredoxin-1.
AB  - Thioredoxin-1 (TRX-1) is a redox-active protein involved in scavenging reactive
      oxygen species and regulating redox-sensitive transcription factors. TRX-1 is
      induced in various inflammatory conditions and shows cytoprotective action. We
      investigated the roles of TRX-1 in the host defense mechanism against
      Helicobacter felis (H. felis) infection. Transgenic (TG) mice overexpressing
      human TRX-1 and wild-type (WT) mice were orally inoculated with H. felis. After 2
      months, histology, oxidative damage, and gene expression of several cytokines,
      including macrophage inflammatory protein-2 (MIP-2), a murine equivalent to
      interleukin (IL)-8, in the gastric mucosa were investigated. Furthermore, the
      effects of TRX-1 on oxidative stress and neutrophil migration were studied both
      in vivo and in vitro. The gastric mucosa was thickened in H. felis-infected WT
      mice, but not in infected TRX-1-TG mice. Histologically, all H. felis-infected WT
      mice developed moderate-to-severe gastritis, whereas the development of gastritis
      was significantly suppressed in infected TRX-1-TG mice. Oxidative damage markers,
      8-hydroxy-2'-deoxyguanosine and malondialdehyde, increased in the stomach of
      infected WT mice, but not TRX-1-TG mice. Upregulation of IL-1beta and tumor
      necrosis factor-alpha gene expression in H. felis-infected TRX-1-TG mice was
      significantly lower than in WT mice. However, upregulation of MIP-2 and IL-7 was
      not different between the two groups. TRX-1 suppressed oxidative cytotoxicity and
      DNA damage, and inhibited neutrophil migration both in vivo and in vitro. The
      present study suggests that overexpression of TRX-1 suppresses H. felis-induced
      gastritis by inhibiting chemotaxis of neutrophils and reducing oxidative stress.

PMID- 15965490
TI  - Reversibility of experimental rabbit liver cirrhosis by portal collagenase
      administration.
AB  - The regression of cirrhosis is associated with increased intrahepatic
      collagenolytic enzyme activity. We investigated whether collagenase
      supplementation via portal vein infusion can retard cirrhosis development and/or
      reverse cirrhosis. In all, 35 rabbits were initially assigned to study. However,
      because of high surgical mortality and infection, only 15 animals completed
      study. Four normal controls (group I) received olive oil subcutaneously (SC) for
      12 weeks followed by normal saline portal perfusion for 12 weeks. Four (group II)
      received CCl(4) SC for 6 weeks followed by portal vein collagenase, 6 mg twice
      weekly, plus SC CCl(4) for 6 additional weeks and then killed. Four rabbits
      (group III) received CCl(4) SC for 12 weeks and then 6 mg of collagenase portally
      for 12 weeks, while three control rabbits (group IV) received CCl(4) for 12 weeks
      followed by saline for 12 weeks. After 12 weeks of CCl(4), liver hydroxyproline
      content of collagenase-treated group II (361.1+/-106.6 microg/g) was
      significantly reduced compared with group III+IV that had not yet received
      collagenase (589.0+/-162.9 microg/g; P<0.05). In the main comparison,
      hydroxyproline content of collagenase-treated group III (177.5+/-35.6 microg/g)
      was significantly decreased compared with saline-treated controls (446.3+/-150.1
      microg/g; P<0.01). Further, liver histology showed complete regression of
      cirrhosis in the collagenase-treated animals. No toxicity of liver, kidney, lung,
      brain or heart was observed histologically. Anaphylaxis occurred in 2/35 original
      animals (one fatal). In conclusion, this study provides 'proof of principle' that
      collagenase portal administration can retard cirrhosis development and speed
      regression of established cirrhosis in the rabbit CCl(4) model. Potential
      application to humans is premature, but feasible, if these findings are confirmed
      in additional animal studies.

PMID- 15965491
TI  - Intracellular signalling controlling integrin activation in lymphocytes.
AB  - Since the discovery that integrins at the surface of lymphocytes undergo dynamic
      changes in their adhesive activity after stimulation through the T-cell receptor
      or stimulation with chemokines, intensive research has been carried out in an
      attempt to clarify the signalling events that lead to the activation of
      integrins. Whereas structural studies have provided us with a vivid picture of
      the conformational flexibility of integrins, the signalling pathways that
      regulate these conformational changes (known as inside-out signalling) have been
      elusive. However, as I discuss here, recent studies have provided new insight
      into the pathways that control the regulation of integrin activity and the
      coordination of complex cellular functions, such as the homing of lymphocytes and
      the formation of an immunological synapse.

PMID- 15965492
TI  - Killing time for cancer cells.
AB  - As the signalling pathways that control cellular proliferation and death are
      unravelled, a range of targets have emerged as candidates for molecular cancer
      therapy. For their survival, cancer cells depend on a few highly activated
      signalling pathways; inhibition of these pathways has a strong apoptotic effect
      and can lead to tumour regression. But drugs that exploit this weakness, such as
      imatinib, have not cured patients: withdrawal of the drug leads to disease
      recurrence, and sustained treatment leads to the emergence of drug-resistant
      clones. Can cancer be cured, or will it have to be controlled as a chronic
      disease?

PMID- 15965493
TI  - Repopulation of cancer cells during therapy: an important cause of treatment
      failure.
AB  - Radiotherapy and chemotherapy are given in multiple doses, which are spaced out
      to allow the recovery of normal tissues between treatments. However, surviving
      cancer cells also proliferate during the intervals between treatments and this
      process of repopulation is an important cause of treatment failure. Strategies
      developed to overcome repopulation have improved clinical outcomes, and now new
      strategies to inhibit repopulation are emerging in parallel with advances in the
      understanding of underlying biological mechanisms.

PMID- 15965494
TI  - The anaemia of cancer: death by a thousand cuts.
AB  - Cancer has a negative systemic impact on its host in addition to its local or
      metastatic effects, and no cancer complication is more ubiquitous than anaemia, a
      condition for which there is now a specific remedy, the recombinant growth factor
      erythropoietin. This is not a trivial therapeutic consideration, because cancer
      associated anaemia has an adverse influence on survival regardless of tumour
      type. However, the pharmacological correction of anaemia with recombinant
      erythropoietin could promote tumour growth, whereas the use of tumour-necrosis
      factor-alpha (TNFalpha) and TNF-related apoptosis-inducing ligand as antitumour
      agents could exacerbate anaemia, thereby perpetuating tissue hypoxia and tumour
      progression.

PMID- 15965495
TI  - M(2) and M(3) muscarinic receptor-mediated contractions in longitudinal smooth
      muscle of the ileum studied with receptor knockout mice.
AB  - Isometric contractile responses to carbachol were studied in ileal longitudinal
      smooth muscle strips from wild-type mice and mice genetically lacking M(2) or
      M(3) muscarinic receptors, in order to characterize the mechanisms involved in
      M(2) and M(3) receptor-mediated contractile responses. Single applications of
      carbachol (0.1-100 microM) produced concentration-dependent contractions in
      preparations from M(2)-knockout (KO) and M(3)-KO mice, mediated via M(3) and M(2)
      receptors, respectively, as judged by the sensitivity of contractile responses to
      blockade by the M(2)-preferring antagonist methoctramine (300 nM) or the M(3)
      preferring antagonist 4-DAMP (30 nM). The M(2)-mediated contractions were
      mimicked in shape by submaximal stimulation with high K(+) concentrations (up to
      35 mM), almost abolished by voltage-dependent Ca(2+) channel (VDCC) antagonists
      or depolarization with 140 mM K(+) medium, and greatly reduced by pertussis toxin
      (PTX) treatment. The M(3)-mediated contractions were only partially inhibited by
      VDCC antagonists or 140 mM K(+)-depolarization medium, and remained unaffected by
      PTX treatment. The contractions observed during high K(+) depolarization
      consisted of different components, either sensitive or insensitive to
      extracellular Ca(2+). The carbachol contractions observed with wild-type
      preparations consisted of PTX-sensitive and -insensitive components. The PTX
      sensitive component was functionally significant only at low carbachol
      concentrations. The results suggest that the M(2) receptor, through PTX-sensitive
      mechanisms, induces ileal contractions that depend on voltage-dependent Ca(2+)
      entry, especially associated with action potential discharge, and that the M(3)
      receptor, through PTX-insensitive mechanisms, induces contractions that depend on
      voltage-dependent and -independent Ca(2+) entry and intracellular Ca(2+) release.
      In intact tissues coexpressing M(2) and M(3) receptors, M(2) receptor activity
      appears functionally relevant only when fractional receptor occupation is
      relatively small.

PMID- 15965496
TI  - Distinct mixtures of muscarinic receptor subtypes mediate inhibition of
      noradrenaline release in different mouse peripheral tissues, as studied with
      receptor knockout mice.
AB  - The muscarinic heteroreceptors modulating noradrenaline release in atria, urinary
      bladder and vas deferens were previously studied in mice in which the M(2) or the
      M(4) muscarinic receptor genes had been disrupted. These experiments showed that
      these tissues possessed both M(2) and non-M(2) heteroreceptors. The analysis was
      now extended to mice in which either the M(3), both the M(2) and the M(3), or
      both the M(2) and the M(4) genes had been disrupted (M(3)-knockout, M(2/3)
      knockout and M(2/4)-knockout). Tissues were preincubated with (3)H-noradrenaline
      and then stimulated electrically (20 pulses per 50 Hz). In wild-type atria,
      carbachol (0.01-100 microM) decreased the electrically evoked tritium overflow by
      maximally 60-78%. The maximum inhibition of carbachol was reduced to 57% in M(3)
      knockout and to 23% in M(2/4)-knockout atria. Strikingly, the effect of carbachol
      was abolished in M(2/3)-knockout atria. In wild-type bladder, carbachol (0.01-100
      microM) reduced the evoked tritium overflow by maximally 57-71%. This effect
      remained unchanged in the M(3)-knockout, but was abolished in the M(2/4)-knockout
      bladder. In wild-type vas deferens, carbachol (0.01-100 microM) reduced the
      evoked tritium overflow by maximally 34-48%. The maximum inhibition of carbachol
      was reduced to 40% in the M(3)-knockout and to 18% in the M(2/4)-knockout vas
      deferens. We conclude that the postganglionic sympathetic axons of mouse atria
      possess M(2) and M(3), those of the urinary bladder M(2) and M(4), and those of
      the vas deferens M(2), M(3) and M(4) release-inhibiting muscarinic receptors.

PMID- 15965497
TI  - Modulation of voltage-dependent Ba2+ currents in the guinea-pig gastric antrum by
      cyclic nucleotide-dependent pathways.
AB  - We have investigated whether the activation of cAMP- and cGMP-dependent pathways
      modifies the properties of voltage-dependent Ba(2+) currents (I(Ba)) recorded
      from guinea-pig gastric myocytes using patch-clamp techniques. All experiments
      were carried on single smooth muscle cells, dispersed from the circular layer of
      the guinea-pig gastric antrum. Both dibutyryl cAMP (db-cAMP, 0.1-1 mM), a
      membrane-permeable ester of cAMP, and isoproterenol, a selective beta-stimulant,
      inhibited I(Ba) in a concentration-dependent manner. Forskolin, but not dideoxy
      forskolin, an inactive isomer of forskolin, inhibited the peak amplitude of
      I(Ba). In the presence of either Rp-cAMP or the PKA (cAMP-dependent protein
      kinase) inhibitor peptide 5-24 (PKA-IP), neither forskolin nor db-cAMP inhibited
      I(Ba). After establishing a conventional whole-cell recording, the peak amplitude
      of I(Ba) gradually decreased when the catalytic subunit of PKA was included in
      the pipette. The further application of Rp-cAMP reversibly enhanced I(Ba). Sodium
      nitroprusside (0.1-1 mM) and 8-Br-cGMP (0.1-1 mM) also inhibited I(Ba) in a
      concentration-dependent manner. The inhibitory effects of forskolin or db-cAMP on
      I(Ba) were not significantly changed by pretreatment with a cGMP-dependent
      protein kinase (PKG) inhibitor. Similarly, the inhibitory actions of 8-Br-cGMP on
      I(Ba) were not modified by PKA-IP. The membrane-permeable cyclic nucleotides db
      cAMP and 8-Br-cGMP caused little shift of the voltage dependence of the steady
      state inactivation and reactivation curves. Neither of the membrane-permeable
      cyclic nucleotides db-cAMP or 8-Br-cGMP had additive inhibitory effects on I(Ba).
      These results indicate that two distinct cyclic nucleotide-dependent pathways are
      present in the guinea-pig gastric antrum, and that both inhibited I(Ba) in an
      independent manner.

PMID- 15965498
TI  - P2 receptor blockade attenuates fever and cytokine responses induced by
      lipopolysaccharide in rats.
AB  - Adenosine 5'-triphosphate (ATP) has been shown to induce release of cytokines
      implicated in fever, including interleukin(IL)-1beta, IL-6, and tumour necrosis
      factor-alpha (TNF-alpha). The role of ATP-mediated purinergic signalling in fever
      and cytokine release during systemic inflammation was investigated by studying
      the effects of P2 receptor antagonists suramin, pyridoxal-5'-phosphate-6
      azophenyl-2',4'-disulphonic acid (PPADS), and Brilliant Blue G (BBG) on changes
      in body temperature and the increases in plasma levels of IL-1beta, IL-6, and
      TNFalpha induced by bacterial lipopolysaccharide (LPS) in rats. LPS (Escherichia
      coli; 50 microg kg(-1))-induced febrile response was attenuated by suramin (25 mg
      kg(-1) and 100 mg kg(-1)), PPADS (25 mg kg(-1)), and a more selective P2X(7)
      receptor antagonist BBG (100 mg kg(-1)) injected intraperitoneally before the
      induction of fever. The increase in plasma concentrations of IL-1beta and IL-6,
      measured 1 h after LPS treatment, was reduced by PPADS (25 mg kg(-1)) and BBG
      (100 mg kg(-1)). LPS-induced increase in plasma TNF-alpha concentration was also
      markedly attenuated by BBG (100 mg kg(-1)), but not by PPADS (25 mg kg(-1)).
      These data indicate that purinergic signalling plays an important role in the
      mechanisms responsible for the LPS-induced febrile response and increases in the
      levels of circulating cytokines. We suggest that ATP acting via P2X(7) receptors
      induces release of pyrogenic cytokines to mediate fever during systemic
      inflammation.

PMID- 15965499
TI  - The effects of flavoxate hydrochloride on voltage-dependent L-type Ca2+ currents
      in human urinary bladder.
AB  - The effects of flavoxate hydrochloride (Bladderon, piperidinoethyl-3
      methylflavone-8-carboxylate; hereafter referred as flavoxate) on voltage
      dependent nifedipine-sensitive inward Ba(2+) currents in human detrusor myocytes
      were investigated using a conventional whole-cell patch-clamp. Tension
      measurement was also performed to study the effects of flavoxate on K(+)-induced
      contraction in human urinary bladder. Flavoxate caused a concentration-dependent
      reduction of the K(+)-induced contraction of human urinary bladder. In human
      detrusor myocytes, flavoxate inhibited the peak amplitude of voltage-dependent
      nifedipine-sensitive inward Ba(2+) currents in a voltage- and concentration
      dependent manner (K(i) = 10 microM), and shifted the steady-state inactivation
      curve of Ba(2+) currents to the left at a holding potential of -90 mV.
      Immunohistochemical studies indicated the presence of the alpha(1C) subunit
      protein, which is a constituent of human L-type Ca(2+) channels (Ca(V)1.2), in
      the bundles of human detrusor smooth muscle. These results suggest that flavoxate
      caused muscle relaxation through the inhibition of L-type Ca(2+) channels in
      human detrusor.

PMID- 15965500
TI  - The cytoskeletal protein ezrin regulates EC proliferation and angiogenesis via
      TNF-alpha-induced transcriptional repression of cyclin A.
AB  - TNF-alpha modulates EC proliferation and thereby plays a central role in new
      blood vessel formation in physiologic and pathologic circumstances. TNF-alpha is
      known to downregulate cyclin A, a key cell cycle regulatory protein, but little
      else is known about how TNF-alpha modulates EC cell cycle and angiogenesis. Using
      primary ECs, we show that ezrin, previously considered to act primarily as a
      cytoskeletal protein and in cytoplasmic signaling, is a TNF-alpha-induced
      transcriptional repressor. TNF-alpha exposure leads to Rho kinase-mediated
      phosphorylation of ezrin, which translocates to the nucleus and binds to cell
      cycle homology region repressor elements within the cyclin A promoter.
      Overexpression of dominant-negative ezrin blocks TNF-alpha-induced modulation of
      ezrin function and rescues cyclin A expression and EC proliferation. In vivo,
      blockade of ezrin leads to enhanced transplanted EC proliferation and
      angiogenesis in a mouse hind limb ischemia model. These observations suggest that
      TNF-alpha regulates angiogenesis via Rho kinase induction of a transcriptional
      repressor function of the cytoskeletal protein ezrin and that ezrin may represent
      a suitable therapeutic target for processes dependent on EC proliferation.

PMID- 15965501
TI  - Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and
      CD8 T cells.
AB  - To examine the impact of tumors on the immune system, we compared global gene
      expression profiles of peripheral blood T cells from previously untreated
      patients with B cell chronic lymphocytic leukemia (CLL) with those from age
      matched healthy donors. Although the cells analyzed were not part of the
      malignant clone, analysis revealed differentially expressed genes, mainly
      involved in cell differentiation in CD4 cells and defects in cytoskeleton
      formation, vesicle trafficking, and cytotoxicity in CD8 cells of the CLL
      patients. In coculture experiments using CLL cells and T cells from healthy
      allogeneic donors, similar defects developed in both CD4 and CD8 cells. These
      changes were induced only with direct contact and were not cytokine mediated.
      Identification of the specific pathways perturbed in the T cells of cancer
      bearing patients will allow us to assess steps to repair these defects, which
      will likely be required to enhance antitumor immunity.

PMID- 15965502
TI  - Transplantation of spermatogonial stem cells isolated from leukemic mice restores
      fertility without inducing leukemia.
AB  - More than 70% of patients survive childhood leukemia, but chemotherapy and
      radiation therapy cause irreversible impairment of spermatogenesis. Although
      autotransplantation of germ cells holds promise for restoring fertility,
      contamination by leukemic cells may induce relapse. In this study, we isolated
      germ cells from leukemic mice by FACS sorting. The cell population in the high
      forward-scatter and low side-scatter regions of dissociated testicular cells from
      leukemic mice were analyzed by staining for MHC class I heavy chain (H-2K/H-2D)
      and for CD45. Cells that did not stain positively for H-2K/H-2D and CD45 were
      sorted as the germ cell-enriched fraction. The sorted germ cell-enriched
      fractions were transplanted into the testes of recipient mice exposed to
      alkylating agents. Transplanted germ cells colonized, and recipient mice
      survived. Normal progeny were produced by intracytoplasmic injection of sperm
      obtained from recipient testes. When unsorted germ cells from leukemic mice were
      transplanted into recipient testes, all recipient mice developed leukemia. The
      successful birth of offspring from recipient mice without transmission of
      leukemia to the recipients indicates the potential of autotransplantation of germ
      cells sorted by FACS to treat infertility secondary to anticancer treatment for
      childhood leukemia.

PMID- 15965518
TI  - Jiri Janata, Georgia Institute of Science and Technology.

PMID- 15965503
TI  - Claudin-1 regulates cellular transformation and metastatic behavior in colon
      cancer.
AB  - Disruption of the cell-cell junction with concomitant changes in the expression
      of junctional proteins is a hallmark of cancer cell invasion and metastasis. The
      role of adherent junction proteins has been studied extensively in cancer, but
      the roles of tight junction (TJ) proteins are less well understood. Claudins are
      recently identified members of the tetraspanin family of proteins, which are
      integral to the structure and function of TJs. Recent studies show changes in
      expression/cellular localization of claudins during tumorigenesis; however, a
      causal relationship between claudin expression/localization and cancer has not
      been established. Here, we report an increased expression of claudin-1 in human
      primary colon carcinoma and metastasis and in cell lines derived from primary and
      metastatic tumors. We also report frequent nuclear localization of claudin-1 in
      these samples. Genetic manipulations of claudin-1 expression in colon cancer cell
      lines induced changes in cellular phenotype, with structural and functional
      changes in markers of epithelial-mesenchymal transition. Furthermore, we
      demonstrate that changes in claudin-1 expression have significant effects on
      growth of xenografted tumors and metastasis in athymic mice. We further provide
      data suggesting that the regulation of E-cadherin expression and beta-catenin/Tcf
      signaling is a possible mechanism underlying claudin-1-dependent changes.

PMID- 15965519
TI  - Speciation analysis with HPLC-mass spectrometry: time to take stock.

PMID- 15965521
TI  - Synchrotron radiation energy-dispersive X-ray diffraction analysis of salt
      distribution in Lepine limestone.
AB  - We describe an analytical application of synchrotron radiation energy-dispersive
      diffraction tomography to map the distribution of crystalline sodium sulfate
      deposited by evaporation from solution within a building limestone.

PMID- 15965520
TI  - Molecular beacons for bioanalytical applications.
AB  - Molecular beacons (MBs) are hairpin-shaped oligonucleotides that contain both
      fluorophore and quencher moieties. They act like switches and are normally in a
      closed state, when the fluorophore and the quencher are brought together to turn
      "off" the fluorescence. When prompted to undergo conformational changes that open
      the hairpin structure, the fluorophore and the quencher are separated, and
      fluorescence is turned "on." This Education will outline the principles of MBs
      and discuss recent bioanalytical applications of these probes for in vitro RNA
      and DNA monitoring, biosensors and biochips, real-time monitoring of genes and
      gene expression in living systems, as well as the next generation of MBs for
      studies on proteins, the MB aptamers. These important applications have shown
      that MBs hold great potential in genomics and proteomics where real-time
      molecular recognition with high sensitivity and excellent specificity is
      critical.

PMID- 15965522
TI  - Ultra-sensitive trace analysis of cyanide water pollutant in a PDMS microfluidic
      channel using surface-enhanced Raman spectroscopy.
AB  - Rapid and highly sensitive trace analysis of cyanide water pollutant in an
      alligator teeth-shaped PDMS microfluidic channel was investigated using surface
      enhanced Raman spectroscopy. Compared with previously reported analytical
      methods, the detection sensitivity was enhanced by several orders of magnitude.

PMID- 15965523
TI  - Paracetamol voltammetric microsensors based on electrocopolymerized-molecularly
      imprinted film modified carbon fiber microelectrodes.
AB  - A molecularly imprinted polymer is presented as a carbon fiber microelectrode
      coating for determining the presence of paracetamol. The polymeric film was
      obtained by electrocopolymerization of o-phenylenediamine and aniline in the
      presence of the template molecule, through the use of cyclic voltammetry. After
      removing the template, the signals of the microsensor were converted into
      physical ones by a voltammetric transductor using square wave voltammetry.
      Various parameters influencing the electropolymerization and voltammetric
      determination processes were examined and optimized. The response of the
      imprinted microsensor to paracetamol was linearly proportional to its
      concentration over the range 6.5 x 10(-6) to 2.0 x 10(-3) mol l(-1), with good
      stability and reproducibility (RSD < 5.6%). The detection limit was 1.5 microM.
      Under the experimental conditions used the voltammetric microsensor was able to
      differentiate between paracetamol and other closely structurally-related
      compounds present in biological fluids, such as certain catecholamines.

PMID- 15965524
TI  - Rapid monitoring of antibiotics using Raman and surface enhanced Raman
      spectroscopy.
AB  - Comparatively few studies have explored the ability of Raman spectroscopy for the
      quantitative analysis of microbial secondary metabolites in fermentation broths.
      In this study we investigated the ability of Raman spectroscopy to differentiate
      between different penicillins and to quantify the level of penicillin in
      fermentation broths. However, the Raman signal is rather weak, therefore the
      Raman signal was enhanced using surface enhanced Raman spectroscopy (SERS)
      employing silver colloids. It was difficult by eye to differentiate between the
      five different penicillin molecules studied using Raman and SERS spectra,
      therefore the spectra were analysed by multivariate cluster analysis. Principal
      components analysis (PCA) clearly showed that SERS rather than the Raman spectra
      produced reproducible enough spectra to allow for the recovery of each of the
      different penicillins into their respective five groups. To highlight this
      further the first five principal components were used to construct a dendrogram
      using agglomerative clustering, and this again clearly showed that SERS can be
      used to identify which penicillin molecule was being analysed, despite their
      molecular similarities. With respect to the quantification of penicillin G it was
      shown that Raman spectroscopy could be used to quantify the amount of penicillin
      present in solution when relatively high levels of penicillin were analysed (>50
      mM). By contrast, the SERS spectra showed reduced fluorescence, and improved
      signal to noise ratios from considerably lower concentrations of the antibiotic.
      This could prove to be advantageous in industry for monitoring low levels of
      penicillin in the early stages of antibiotic production. In addition, SERS may
      have advantages for quantifying low levels of high value, low yield, secondary
      metabolites in microbial processes.

PMID- 15965525
TI  - A new chemically amplified electrochemical system for the detection of biological
      affinity reactions: direct and competitive biotin assay.
AB  - Quantitation of biological affinity reactions by a newly developed chemically
      amplified electrochemical detection method was demonstrated with the biotin
      avidin binding pair. In the method, ruthenium tris(2,2'-bipyridine)(Ru-bipy) was
      used as an electrochemical signal-generating tag. Its oxidation current on an
      indium tin oxide (ITO) electrode was amplified with a sacrificial electron donor,
      oxalate. Because oxalate itself produced negligible current on the electrode, the
      signal-to-background ratio was greatly enhanced in comparison with other chemical
      amplification systems. Although the Ru-bipy/oxalate redox couple has been
      employed previously in electrochemiluminescent and photoelectrochemical
      detection, its use in a catalytic amperometric detection of biological binding
      assays has not been reported. To implement the method in the detection of biotin
      avidin recognition, avidin was immobilized on an ITO electrode, and was reacted
      with biotin in solution. Immobilization of avidin by passive adsorption was found
      to be relatively stable under the condition of the affinity reaction. In the
      direct assay, biotin labelled with Ru-bipy was recognized by avidin and
      accumulated on the electrode surface, which was then detected electrochemically
      in the presence of oxalate. A linear relationship between electrochemical current
      and biotin concentration was obtained in the range of 1-300 ng mL(-1). In the
      competitive assay, a mixed solution of unlabelled biotin (the analyte) of various
      concentrations and 100 ng mL(-1) labelled biotin was reacted with avidin on the
      surface. As the concentration of the unlabelled biotin increased, less labelled
      biotin bound to avidin, leading to a reduction in the electro-catalytical
      response of Ru-bipy. A detection limit of 1 ng mL(-1) biotin was obtained in the
      competitive assay, which is close to the sensitivity of some enzyme-labelled
      amperometric assays.

PMID- 15965526
TI  - Molecular imprinting-chemiluminescence determination of trimethoprim using
      trimethoprim-imprinted polymer as recognition material.
AB  - A new molecular imprinting-chemiluminescence method for the determination of
      trimethoprim was developed, in which trimethoprim-imprinted polymer was used as
      the molecular recognition material and the CL reaction of trimethoprim with
      potassium permanganate in acidic medium was used as the detection system. The CL
      intensity responds linearly to the concentration of trimethoprim within the 5.0 x
      10(-8)-5.0 x 10(-6) g mL(-1) range (r= 0.9983) with a detection limit of 2 x 10(
      8) g mL(-1). The relative standard deviation for the determination of 1.0 x 10(
      7) g mL(-1) trimethoprim solutions is 4.8% (n= 9). The method has been applied to
      the determination of trimethoprim in pharmaceutical preparations and body fluids,
      and satisfactory results were obtained.

PMID- 15965528
TI  - Development of a novel UV indicator and dosimeter film.
AB  - A novel UV indicator is described, comprising nanocrystalline particles of
      titania dispersed in a film of a polymer, hydroxyl ethyl cellulose (HEC),
      containing: a mild reducing agent, triethanolamine (TEOA) and a redox indicator,
      methylene blue (MB). The UV indicator film is blue-coloured in the absence of UV
      light and loses colour upon exposure to UV light, attaining within a few min a
      steady-state degree of bleaching that can provide a measure of the irradiance of
      the incident light. The original blue colour of the film returns once the source
      of UV light is removed. The spectral characteristics of a typical UV indicator
      film, and its components, are discussed and the UV-absorbing action of the
      titania particles highlighted. From the measured %bleaching undergone by a
      typical UV indicator as a function of light irradiance the indicator appears
      fully bleached, within 7 min, by a UV irradiance of 3 mW cm(-2) or greater. The
      mechanism by which the UV indicator works is described. The reversible nature of
      the UV indicator is removed by covering a typical UV indicator with a thin,
      largely oxygen impermeable, polymer film, such as the regenerated cellulose found
      in Sellotape. The product is a UV dosimeter, the response of which is related to
      the intensity and duration of the incident UV light, as well as the amount of
      titania in the film. A typical UV dosimeter film is fully bleached by 250 mJ cm(
      2) of UV light. The possible use of these novel indicators to measure UV exposure
      levels, irradiance and dose, is discussed.

PMID- 15965527
TI  - Highly sensitive and selective room-temperature phosphorescence determination of
      thiabendazole by the supramolecular interaction of thiabendazole/beta
      cyclodextrin/triton X-100.
AB  - A strong and stable room temperature phosphorescence (RTP) signal
      (lambda(ex)/lambda(em) = 298/481 nm) resulting from a 1:1:1 beta-cyclodextrin
      (beta-CD)/thiabendazole (TBZ)/triton X-100 (TX-100) supramolecular ternary
      inclusion complex was induced by KI as a heavy atom perturber. Based on the heavy
      atom induced RTP, a new phosphorescence method for TBZ determination was
      established. The analytical curve of TBZ gave a linear range of 20-820 ng mL(-1)
      with a detection limit and relative standard deviation of 2.1 ng mL(-1) and 1.9%,
      respectively. The interference of 46 coexisting substances was studied. Compared
      with the method using a chemical oxygen scavenger, this method is simpler as
      deoxygenation of the solution is not required. The detection limit and the heavy
      atom concentration of the proposed method were decreased about 8 and 4 times,
      respectively. The lifetime of the phosphorescence was prolonged 9 times and the
      pH range was greatly broadened. The proposed method has been successfully applied
      to the determination of TBZ in tap water, lake water and pineapples.

PMID- 15965529
TI  - An automated electrokinetic continuous sample introduction system for
      microfluidic chip-based capillary electrophoresis.
AB  - An automated and continuous sample introduction system for microfluidic chip
      based capillary electrophoresis (CE) was developed in this work. An efficient
      world-to-chip interface for chip-based CE separation was produced by horizontally
      connecting a Z-shaped fused silica capillary sampling probe to the sample loading
      channel of a crossed-channel chip. The sample presentation system was composed of
      an array of bottom-slotted sample vials filled alternately with samples and
      working electrolyte, horizontally positioned on a programmable linearly moving
      platform. On moving the array from one vial to the next, and scanning the probe,
      which was fixed with a platinum electrode on its tip, through the slots of the
      vials, a series of samples, each followed by a flow of working electrolyte was
      continuously introduced electrokinetically from the off-chip vials into the
      sample loading channel of the chip. The performance of the system was
      demonstrated in the separation and determination of FITC-labeled arginine and
      phenylalanine with LIF detection, by continuously introducing a train of
      different samples. Employing 4.5 kV sampling voltage (1000 V cm(-1) field
      strength) for 30 s and 1.8 kV separation voltage (400 V cm(-1) field strength)
      for 70 s, throughputs of 36 h(-1) were achieved with <1.0% carryover and 4.6, 3.2
      and 4.0% RSD for arginine, FITC and phenylalanine, respectively (n = 11). Net
      sample consumption was only 240 nL for each sample.

PMID- 15965530
TI  - Analysis of crystalline phases in airborne particulates by grazing incidence X
      ray diffractometry.
AB  - Amounts of crystalline phases of airborne particulates collected on a silicon
      wafer (10 x 10 mm) using a high-volume air sampler were analyzed by grazing
      incidence X-ray diffractometry (GIXD). Airborne particulates were classified into
      five size ranges (1.09-10.5 microm) with a cascade impactor attached on the
      sampling ports of the high-volume air sampler. GIXD was used throughout this
      analysis to obtain better sensitivity for small amounts of airborne particulates
      on the silicon wafer. Calibration standards on the silicon wafer for the
      diffractometric determination were prepared by the suspension droplet method of
      the crystalline standards dispersed in cyclohexane. Analytical lines were (020)
      for gypsum, (101) for quartz, (104) for calcite, (200) for halite, and (110) for
      sal ammoniac. The sample and the calibrating standards were heated at 350 degrees
      C for 2 h to avoid mutual interference with gypsum (041 and 221) when calcite and
      halite were determined. The GIXD method enables us to determine 0.23-13.2 microg
      of gypsum, quartz, calcite, halite and sal ammoniac in 0.110-0.233 mg of airborne
      particulates on the silicon wafer.

PMID- 15965531
TI  - Determination of endocrine disruptors in environmental waters using
      poly(acrylamide-vinylpyridine) monolithic capillary for in-tube solid-phase
      microextraction coupled to high-performance liquid chromatography with
      fluorescence detection.
AB  - A method for the determination of endocrine disruptors, bisphenol A and 17alpha
      ethinylestradiol, in environmental water samples was developed using in-tube
      solid-phase microextraction followed by liquid chromatography and fluorescence
      detection. A poly(acrylamide-vinylpyridine) monolithic capillary column was
      applied as the extraction media in view of its greater phase ratio than open
      tubular capillaries and thus higher extraction efficiency. After optimizing the
      extraction conditions, bisphenol A and 17alpha-ethinylestradiol were extracted
      directly from water samples in a wide dynamic linear range of 0.5-1000 ng mL(-1),
      with the detection limits obtained as 0.064 and 0.12 ng mL(-1), respectively. The
      precision of the method was satisfactory with the intraday and interday RSD
      values smaller than 7.2%. Environmental water samples of different sources were
      successfully analyzed with the presented method and the monolithic capillary was
      proved to be robust and reusable in analyzing real water samples.

PMID- 15965532
TI  - Near infrared Raman spectroscopic mapping of native brain tissue and intracranial
      tumors.
AB  - This study assessed the diagnostic potential of Raman spectroscopic mapping by
      evaluating its ability to distinguish between normal brain tissue and the human
      intracranial tumors gliomas and meningeomas. Seven Raman maps of native specimens
      were collected ex vivo by a Raman spectrometer with 785 nm excitation coupled to
      a microscope with a motorized stage. Variations within each Raman map were
      analyzed by cluster analysis. The dependence of tissue composition on the tissue
      type in cluster averaged Raman spectra was shown by linear combinations of
      reference spectra. Normal brain tissue was found to contain higher levels of
      lipids, intracranial tumors have more hemoglobin and lower lipid to protein
      ratios, meningeomas contain more collagen with maximum collagen content in normal
      meninges. One sample was studied without freezing. Whereas tumor regions did not
      change significantly, spectral changes were observed in the hemoglobin component
      after snap freezing and thawing to room temperature. The results constitute a
      basis for subsequent Raman studies to develop classification models for diagnosis
      of brain tissue.

PMID- 15965533
TI  - Development of a highly sensitive monoclonal antibody based ELISA for detection
      of benzo[a]pyrene in potable water.
AB  - In Europe, a limit value of 10 ng L(-1) was set by the European Commission for
      benzo[a]pyrene (B[a]P) in water intended for human consumption (Council Directive
      98/83/EC) and, therefore, sensitive and reliable methods are needed to evaluate
      its presence. We report here on the development of a highly sensitive indirect
      competitive ELISA for the detection of B[a]P in potable water. Fourteen
      monoclonal antibodies were generated in mice using novel B[a]P derivatives. The
      immunoassay with the least interference and the best sensitivity was optimized
      and characterized. As co-solvent, ten percent methanol (v/v) was determined as
      the optimum concentration for B[a]P solubilization for use with the developed
      ELISA. With the purified antibody (clone 22F12) the average IC50 for B[a]P and
      corresponding detection limit at a signal:noise (S/N) ratio of 3 was 65 ng L(-1)
      and 24 ng L(-1), respectively. From the 16 EPA-designated PAHs, only chrysene,
      indeno[1,2,3-cd]pyrene, and benzo[b]fluoranthene showed a cross-reactivity (CR)
      higher than 20%. No CR was observed for two- and three-ringed aromatics as well
      as dibenz[ah]anthracene and benzo[ghi]perylene. The effect of pH value (range 6.5
      9.5), ionic strength (specific electric conductivity 1 microS cm(-1)-2.5 mS cm(
      1)), and inorganic ions (sodium, copper, iron, aluminium, manganese, chloride,
      sulfate, nitrate, and nitrite at maximum permissible levels according to the
      Council Directive) on both signal and sensitivity of the ELISA was studied. No
      significant influence of these parameters on the ELISA competition curve was
      found. We suggest that the optimized ELISA can be used to monitor potable water
      samples without previous extraction from the samples. The assay should facilitate
      the cleanup of B[a]P contaminated sites where B[a]P levels fall close to the
      limit value of the new drinking water directive.

PMID- 15965534
TI  - Identification of the estrogen receptor Cd-binding sites by chemical
      modification.
AB  - The widely reported interactions of the estrogen receptor (ER) with endocrine
      disrupting chemicals (EDCs) present in the environment gave raise to public
      concern and led to a number of screening and testing initiatives on the
      international level. Recent studies indicated that certain heavy metals,
      including cadmium, can mimic the effects of the endogenous estrogen receptor
      agonist 17beta-estradiol, and lead to estrogen receptor activation. Previous
      studies of the chimeric proteins, which incorporate the ligand-binding domain of
      the human ER, identified Cys 381, Cys 447, Glu 523, His 524 and Asp 538 as
      possible sites of interactions with cadmium. In the present study we utilized the
      rainbow trout ER ligand-binding domain fused to glutathione-S-transferase, and
      used Cd-shielding against various types of chemical modification of the fusion
      protein to study non-covalent interactions between the ER and Cd. The
      distribution of exposed and shielded residues allowed to identify amino acid
      residues involved in the interaction. Our data indicated preferential protection
      of Cys groups by cadmium, suggesting their involvement in the interaction. This
      supports data found in the literature on the strong binding affinity of the thiol
      group towards metals. However, not all Cys in the fusion protein sequence were
      protected against chemical modification, illustrating the importance of their
      chemical environment. In general, the location of rtER-LBD Cys residues
      implicated in Cd interactions did not confirm assignments made by alanine
      scanning mutagenesis for the hER, probably due to differences in experimental
      setup and fusion proteins used. The involvement of other functional groups such
      as carboxylic acids in the Cd interactions, though not confirmed, can not be
      completely ruled out due to the general limitations of the chemical modification
      approach discussed in detail. Suggestions for an improved experimental setup were
      made.

PMID- 15965535
TI  - Ultrasensitive voltammetric detection of trace heavy metal ions using carbon
      nanotube nanoelectrode array.
AB  - We describe an ultrasensitive voltammetric detection of trace heavy metal ions
      using nanoelectrode arrays (NEAs) that are based on low-site density carbon
      nanotubes (CNTs). The NEAs were prepared by sealing the side-walls of CNTs with
      an epoxy passive layer that reduces the current leakage and eliminates the
      electrode capacitance, leading to a low background current. This provides a high
      signal-to-noise ratio. The CNTs-NEAs coated with a bismuth film were used
      successfully for voltammetric detection of trace cadmium(II) and lead(II) at the
      sub-ppb level. The detection limit of 0.04 microg L(-1) was obtained under
      optimum experimental conditions. The attractive behavior of the new carbon NEA
      sensing platform holds great promise for onsite environmental monitoring and
      biomonitoring of toxic metals.

PMID- 15965536
TI  - Determination of aromatic hydrotropic drugs in pharmaceutical preparations by the
      surfactant-binding degree method.
AB  - An aggregation parameter-based analytical approach, the surfactant-dye binding
      degree (SDBD) method, was used, for the first time, to determine aromatic
      hydrotropic compounds. The anionic dye Coomassie Brilliant Blue G (CBBG) was used
      as inductor of didodecyldimethylammonium bromide (DDABr) aggregates, whose
      formation was monitored from changes in the spectral features of the dye.
      Interactions between hydrotrope and DDABr molecules resulted in a decrease of the
      degree of binding of the cationic surfactant to CBBG, which was proportional to
      the concentration of hydrotrope in the aqueous solution. The CBBG-DDABr
      hydrotrope chemical system was found to fit to the mathematical expression
      previously derived for the determination of amphiphilic compounds. The hydrotrope
      surfactant bond strength determined the sensitivity achieved for the
      determination of hydrotropic compounds, which was highly dependent on the
      molecular structure of the analyte. The high precision (the relative standard
      deviation for 7 mg l(-1) of salicylic acid was 0.8%), rapidity (measurements were
      performed in a few minutes) and low cost (in both instrumentation and reactants)
      of the proposed method, made it especially suitable for quality control. The
      practical analytical applicability of the SDBD method for the control of
      hydrotropic drugs in pharmaceutical preparations was demonstrated by quantifying
      salicylic acid and acetyl salicylic acid in liquid (solutions) and solid
      (tablets, granulates, unguents, gels and creams) samples, which were directly
      analyzed after dissolution of the samples.

PMID- 15965537
TI  - Exploring supramolecular interactions and architectures by scanning force
      microscopies.
AB  - The development of new methodologies based on scanning force microscopy (SFM) has
      made it possible to map topographies, chemical functionalities, and numerous
      other physicochemical properties of complex assemblies, to unravel dynamic
      processes, to measure forces generated along a reaction coordinate, to
      nanopattern surfaces and to nanomanipulate objects. This tutorial review
      highlights the most recent applications of these SFM-based capabilities, on and
      beyond imaging, to the exploration of supramolecular interactions and
      architectures, to the fabrication of smart materials and to the optimization of
      (nano)devices.

PMID- 15965538
TI  - The chemistry of trifluoromethyl imines and related acetals derived from fluoral.
AB  - Trifluoromethylated nitrogen-containing molecules have been shown to have
      important biological effects and their synthesis is in the focus of the
      pharmaceutical industry. In the last few years, simple nitrogen derivatives of
      fluoral, i.e. imines, acetals and oxazolidines, have emerged as powerful building
      blocks to synthesize these target molecules and relevant precursors. This review
      summarizes the chemistry of these "N-derivatives of fluoral", with special
      highlight on the syntheses of peptidomimetic units (amino alcohols, amino
      acids...) and heterocycles (piperidines, beta-lactams...).

PMID- 15965539
TI  - Enantioselective epoxidation of olefins with chiral metalloporphyrin catalysts.
AB  - The intent of this tutorial review is to cover the recent progress accomplished
      in iron and manganese porphyrin-catalyzed enantioselective epoxidation of
      terminal olefins. The literature is covered up to the beginning of 2005. In the
      first part of the manuscript, we will present the results obtained with simple
      catalysts in the early eighties, before describing the pickets and strapped
      series reported more recently. We will also place a special emphasis on the
      biomimetic approach that oriented most of this research throughout the years. As
      a conclusion, we will demonstrate that easy-to-prepare porphyrin catalysts should
      play an important role in the future and should compete with other well-known,
      successful systems. Among those, the popular titanium tartrate-catalyzed
      Sharpless-Katsuki asymmetric epoxidation allows the conversion of allylic
      alcohols to chiral epoxides with high enantiomeric excesses and high conversion.
      We will also cite the chiral metallosalen complexes independently reported by
      Jacobsen and Katsuki in 1990. Using manganese-salens, cis-1,2-disubstituted,
      trisubstituted and some tetrasubstituted olefins are efficiently epoxidized with
      high enantiomeric excess. However, they suffer from two major drawbacks. They
      often require low temperature for the epoxidation of monosubstituted (57% ee for
      styrene at 5 degrees C; 80% at -78 degrees C). More importantly, they proceed
      with low turnover numbers, TON (TON approximately 40 for styrene). More recently,
      a new approach involving metal-free chiral dioxiranes was also reported. In some
      cases, they constitute an interesting alternative to the more common systems
      previously discussed. Compared to the three pre-cited systems, chiral
      metalloporphyrins allow the enantioselective epoxidation of unfunctionalized
      terminal olefins with high enantiomeric excess (>97% ee for styrene) and
      impressive turnover numbers (>16000) when PhIO is used as oxidant. These results
      highlight the remarkable potential of porphyrin-based catalysts.

PMID- 15965540
TI  - 1,1'-Di(heteroatom)-functionalised ferrocenes as [N,N], [O,O] and [S,S] chelate
      ligands in transition metal chemistry.
AB  - Dppf is one of the most useful and popular ligands in coordination chemistry. Its
      overwhelming success has overshadowed and arguably even delayed the development
      and use of closely related ferrocene-based ligands with two ligating N, O or S
      atoms. Recently, however, dynamic progress concerning such homo-donor ligands can
      be noted. This tutorial review describes the main results obtained over the past
      decade in order to introduce the reader to an exciting field which currently
      shows particularly rapid development. The material is organised in sections
      according to ligand type, followed by a section which summarises the applications
      reported so far.

PMID- 15965541
TI  - Stereolabile chiral compounds: analysis by dynamic chromatography and stopped
      flow methods.
AB  - Enantiomerization and diastereomerization reactions of chiral compounds play a
      major role in all aspects of chemistry spanning a wide bridge from drug
      development to supramolecular chemistry. Traditionally, these reactions are
      studied by variable-temperature NMR spectroscopy and chiroptical methods such as
      polarimetry. However, powerful complimentary methods based on chromatography and
      electrophoresis have been developed and applied to a variety of stereolabile
      chiral compounds. This tutorial review explains the principles, applications, and
      limitations of dynamic chromatography and chromatographic and electrophoretic
      stopped-flow analysis for the investigation of isomerization reactions of chiral
      compounds.

PMID- 15965542
TI  - Role of sulfur chirality in the chemical processes of biology.
AB  - Chiral structures profoundly influence chemical and biological processes. While
      chiral carbon biomolecules have received much attention, chirality is also
      possible in certain sulfur compounds; just as with carbon, there can be
      differences in the physiological behavior of chiral sulfur compounds. For
      instance, one drug enantiomer, Nexium (esomeprazole, a chiral sulfoxide), is used
      for its superior clinical properties as a proton pump inhibitor over the racemic
      mixture, Prilosec (Losec, omeprazole). This critical review introduces sulfur
      stereochemistry and nomenclature, and provides a comprehensive approach to chiral
      sulfur compounds and their enzymatic reactions in general and secondary
      metabolism. The major structural types of biological interest are sulfonium
      salts, sulfoxides, and sulfoximines. (103 references).

PMID- 15965543
TI  - Fragile X syndrome: an update and review for the primary pediatrician.
AB  - Fragile X syndrome (FXS) is the most common inherited cause of mental
      retardation. Since the initial identification of the responsible gene more than a
      decade ago, substantial progress has been made in both the clinical aspects of
      the disorder and its mechanistic basis; hence, it is important for primary care
      physicians to be familiar with these advances when providing anticipatory
      guidance. Timely diagnosis allows children to receive early intervention services
      and families to receive genetic counseling. Here the current state of knowledge
      is reviewed and a framework is provided for early recognition and diagnosis,
      along with counseling and treatment implications for the children and family
      members.

PMID- 15965544
TI  - Seizure medications: a review for the primary care pediatrician.

PMID- 15965545
TI  - Disease management in the young diabetic patient: glucose monitoring, coping
      skills, and treatment strategies.
AB  - Type 1 diabetes mellitus was thought to be the prevalent type of diabetes in
      children and adolescents; however, increasing numbers of juvenile patients appear
      to have type 2 diabetes. Management of all diabetes in young patients should
      include regular assessment, careful monitoring for glycemic control and the
      presence of hypoglycemia, and educational training on disease management.
      Hypoglycemic episodes, especially nocturnal events, are frequent in the young
      diabetic patient. Improvements in glycemic control and nocturnal hypoglycemia
      have been observed with continuous subcutaneous insulin infusion and insulin
      glargine. A continuous glucose-monitoring system can provide important insight
      into 24-hour glycemic control. Overall, careful management, monitoring, and
      education can improve glycemic control and yield positive treatment outcomes in
      the child or adolescent with diabetes.

PMID- 15965546
TI  - Effects of stimulant medication on cognitive performance of children with ADHD.
AB  - The effect that treatment with stimulant medication has on the intellectual
      performance of children with attention deficit hyperactivity disorder (ADHD) was
      examined. Thirty-one children diagnosed with ADHD were given a WISC-III before
      any treatment was implemented. At least 1 year later, children were retested. At
      this time, 24 of the children were taking stimulant medications. Children
      receiving medications had significant increases in IQ scores, but no changes were
      found for those not taking medications. Changes in IQ scores were moderately
      related to parents' perceived efficacy of the medication and parent-reported
      compliance with medication but were not strongly related to changes in parent
      reported ADHD symptoms.

PMID- 15965547
TI  - A multimedia violence prevention program increases pediatric residents' and
      childcare providers' knowledge about responding to childhood aggression.
AB  - A pre-post knowledge test using alternate forms was used to determine if a
      multimedia violence prevention program can increase knowledge about management of
      childhood aggression. The participants were pediatric residents and childcare
      workers who attended lectures about aggression management in young children. The
      intervention was a presentation of a 30 minute CD-ROM program, Play Nicely, which
      teaches how to manage aggression in young children ages 1 to 7 years. A pretest
      and posttest multiple-choice knowledge assessment that focused on the program's
      most important recommendations was administered. Childcare workers and pediatric
      residents had significantly increased knowledge scores after viewing the CD-ROM
      demonstration (F=6.8, p = 0.01). Childcare workers' scores improved by 2.6 points
      (p< 0.001) and residents' scores by 3.8 points (p< 0.001). A relatively short CD
      ROM can improve knowledge about how to manage aggression in young children,
      indicating its usefulness as a violence prevention resource.

PMID- 15965548
TI  - Lyme arthritis in 20 children residing in a non-endemic area.
AB  - In non-endemic areas of the country, Lyme disease may not be considered in
      children who present with arthritis. This report details the clinical features of
      Lyme arthritis in 20 children residing in central Virginia. All patients
      presented with transient, often recurrent oligoarthritis of large joints,
      particularly the knee. Most patients were referred with a presumptive diagnosis
      of juvenile rheumatoid arthritis (JRA). This report reiterates the clinical
      presentation of Lyme arthritis in children and reminds physicians to consider the
      diagnosis of Lyme arthritis in children who present with acute arthritis even if
      they reside in a non-endemic area of the country. In addition, it differentiates
      the clinical presentation of Lyme arthritis from JRA.

PMID- 15965549
TI  - Standard-dose and short-term corticosteroid therapy in immunoglobulin-resistant
      Kawasaki disease.
AB  - Six patients with Kawasaki disease (KD) were treated with prednisolone (1 to 2
      mg/kg/day) for 3 days (from days 10 to 12 after the onset of the illness) after
      apparently unsuccessful treatment with intravenous immunoglobulin (IVIG, 2
      g/kg/dose and additional 1 g/kg/dose). Five patients responded immediately to the
      first course of prednisolone infusion. One patient failed to respond to the first
      course of prednisolone therapy, but he did respond to the second 3-day course of
      therapy. None of the patients demonstrated a further progression of coronary
      artery dilatation or any adverse effects. Standard-dose and short-term
      corticosteroid therapy therefore appears to be a safe and effective treatment for
      patients with IVIG-resistant KD.

PMID- 15965550
TI  - Identifying children with pneumonia in the emergency department.
AB  - Emergency physicians need to clinically differentiate children with and without
      radiographic evidence of pneumonia. In this prospective cohort study of 510
      patients 2 to 59 months of age presenting with symptoms of lower respiratory
      tract infection, 100% were evaluated with chest radiography and 44 (8.6%) had
      pneumonia on chest radiography. With use of multivariate analysis, the adjusted
      odds ratio (AOR) and 95% confidence intervals (CI) of the clinical findings
      significantly associated with focal infiltrates were age older than 12 months
      (AOR 1.4, CI 1.1-1.9), RR 50 or greater (AOR 3.5, CI 1.6-7.5), oxygen saturation
      96% or less (AOR 4.6, CI 2.3-9.2), and nasal flaring (AOR 2.2 CI 1.2-4.0) in
      patients 12 months of age or younger. The combination of age older than 12
      months, RR 50 or greater, oxygen saturation 96% or less, and in children under
      age 12 months, nasal flaring, can be used in determining which young children
      with lower respiratory tract infection symptoms have radiographic pneumonia.

PMID- 15965551
TI  - Paroxysmal non-epileptic events resembling seizures in children with otitis
      media.
AB  - Children may frequently present with recurrent spells, which are often thought to
      be seizures. However, there are several benign non-epileptic conditions that
      mimic seizures. A group of 8 children is described who were diagnosed with otitis
      media and presented with recurrent, stereotypic spells suggestive of seizures. A
      paroxysmal phenomenon, in association with otitis media, resembling seizures, has
      not been previously described. These paroxysmal phenomena resembling seizures may
      be related to acute otitis media and should be included in the differential
      diagnosis of paroxysmal non-epileptic events in infants and young children.

PMID- 15965552
TI  - Management and outcomes of intracranial tuberculomas developing during
      antituberculous therapy: case report and review.

PMID- 15965553
TI  - Congenital tuberculosis: a case report.

PMID- 15965554
TI  - Hypocalcemic seizures secondary to nutritional vitamin D deficiency in 3 infants
      fed soy formula.

PMID- 15965555
TI  - CSF Pleocytosis.

PMID- 15965557
TI  - Speculation on how some "glove distribution'' burns may be accidental.

PMID- 15965558
TI  - Atrial fibrillation: the rate or rhythm controversy can it be resolved on the
      basis of clinical trial data?

PMID- 15965559
TI  - Pharmacotherapy of congestive heart failure in elderly patients.
AB  - With longer life expectancy, as well as better survival rates after myocardial
      infarction, the population of elderly patients with congestive heart failure
      steadily increases. Large, randomized, placebo-controlled studies have shown
      significant beneficial effects for several classes of drugs (angiotensin
      converting enzyme inhibitors, angiotensin II receptor blockers, beta-blockers,
      aldosterone antagonists) in patients with congestive heart failure. In most of
      these studies, however, elderly patients were either excluded or represented only
      a minority of the study population. Therefore, the treatment benefit for the
      large population of patients aged 65 and older is still not very well documented.
      In this paper, we critically review the current literature with regard to outcome
      of heart failure therapy in this particular subpopulation.

PMID- 15965560
TI  - Cardiovascular risk of selective cyclooxygenase-2 inhibitors.
AB  - Recently, cyclooxygenase-2 (COX-2) inhibitors (coxibs), a class of drugs intended
      to be painkillers, have created unprecedented controversy because of their
      cardiovascular risk profile. The controversy has affected the patients, health
      care providers, the Food and Drug Administration, and the manufacturers of these
      agents alike. We summarize the mechanisms of actions of this class of agents,
      their cardiovascular risk as evident in multiple trials, the basis of their
      adverse risk profile, and our views on this issue.

PMID- 15965561
TI  - Dietary vitamin e supplementation attenuates hypertension in Dahl salt-sensitive
      rats.
AB  - There is strong evidence that excess dietary salt (NaCl) is a major factor
      contributing to the development of hypertension. Salt-sensitive humans and rats
      develop hypertension even on a normal-salt diet. Salt sensitivity is associated
      with glucose intolerance and insulin resistance in both humans and animal models,
      including Dahl salt-sensitive (DSS) rats. In insulin resistance, impaired glucose
      metabolism leads to elevated endogenous aldehydes that bind sulfhydryl groups of
      membrane proteins, altering calcium channels, and increasing cytosolic free
      calcium ([Ca2+]i) and blood pressure. Vitamin E lowers tissue aldehyde
      conjugates, cytosolic [Ca2+]i, and blood pressure in spontaneously hypertensive
      rats and fructose-induced hypertensive Wistar Kyoto rats, models of insulin
      resistance. This study investigated the effect of a normal-salt diet on tissue
      aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in DSS rats and the
      effect of vitamin E supplementation on blood pressure and associated biochemical
      changes in these animals. Seven-week-old DSS rats were divided into 3 groups of 6
      animals each and treated for 6 weeks with diets as follows: low-salt (0.4% NaCl);
      normal-salt (0.7% NaCl) and normal salt (0.7% NaCl) plus vitamin E (34 mg/kg
      feed). At completion, animals in the normal-salt group had significantly elevated
      systolic blood pressure, cytosolic [Ca2+]i, and tissue aldehyde conjugates
      compared with the low-salt group. They also showed smooth muscle cell hyperplasia
      in small arteries and arterioles of the kidney. Dietary vitamin E supplementation
      significantly attenuated the increase in systolic blood pressure and associated
      biochemical and histopathologic changes.

PMID- 15965562
TI  - Carvedilol mitigates adverse effects of epinephrine during cardiopulmonary
      resuscitation.
AB  - INTRODUCTION: Earlier studies have implicated the adverse effects of beta- and
      alpha(1)-adrenergic receptors during cardiopulmonary resuscitation (CPR). Because
      carvedilol is both a nonselective beta- and alpha1-selective adrenergic receptor
      blocking agent, we hypothesized that pretreatment with carvedilol would convert
      the actions of epinephrine to that of a selective alpha2-agonist. METHODS:
      Ventricular fibrillation (VF) was induced in Sprague-Dawley rats weighing
      approximately 500 g. Animals were randomized to 4 groups of 5 animals each: (1)
      placebo pretreatment and epinephrine treatment, (2) carvedilol pretreatment and
      placebo treatment, (3) carvedilol pretreatment and epinephrine treatment, and (4)
      placebo pretreatment and placebo treatment. Carvedilol (50 microg/kg) was
      injected as a bolus into the right atrium 15 minutes before VF was induced. VF
      was untreated for 8 minutes, after which CPR (chest compression and mechanical
      ventilation) was begun. Epinephrine (30 microg/kg) was injected into the right
      atrium 2 minutes after the start of CPR. Electrical defibrillation was attempted
      after 14 minutes of VF. RESULTS: All but 2 animals were successfully
      resuscitated. Approximately equivalent increases in coronary perfusion pressure
      from 23 +/- 1 mm Hg to 30 +/- 3 mm Hg were observed after the injection of
      epinephrine independently of carvedilol pretreatment. Carvedilol pretreatment
      followed by epinephrine treatment reduced early postresuscitation ventricular
      ectopy (116 +/- 147 vs 834 +/- 380, P < .01) and minimized increases in arterial
      blood lactate at 5 minutes after resuscitation (10.9 +/- 2.1 mmol/L vs 17.4 +/-
      3.5 mmol/L, P < .01). The postresuscitation cardiac index measured 4 hours later
      was increased (307 +/- 43 mL x min(-1) x kg(-1) vs 210 +/- 6 mL x min(-1) x kg(
      1), P < .05). Left ventricular diastolic pressures were decreased (6 +/- 1 vs 14
      +/- 1 mm Hg, P < .05). Animals pretreated with carvedilol survived longer (71 +/-
      1 vs 45 +/- 22 hours, P < .05) and with less postresuscitation neurologic
      deficit. CONCLUSION: After beta- and alpha1-adrenergic blockade with carvedilol
      before inducing cardiac arrest, epinephrine administered during CPR yielded
      better postresuscitation myocardial and neurologic functions and significantly
      increased postresuscitation survival.

PMID- 15965564
TI  - Elevated troponins and the Churg-Strauss syndrome: a case report.
AB  - In a patient with persistently elevated troponin levels but normal ischemic work
      up, a diagnostic dilemma can ensue. This is the case of a 65-year-old woman whose
      only cardiac risk factor was age. She presented repeatedly with chest pain,
      elevated troponins, and consistently elevated eosinophil levels until the fourth
      admission when she presented with multi-organ abnormalities including asthma and
      vasculitis that led to the diagnosis of Churg-Strauss syndrome (CSS). Initiation
      of corticosteroids immediately resolved all of her presenting symptoms; troponin
      and eosinophil levels quickly normalized. Eosinophilia from CSS can lead to multi
      organ damage including the heart. Therefore, one must consider CSS in the
      differential of eosinophilia as early detection and treatment may be critical in
      decreasing morbidity and mortality.

PMID- 15965563
TI  - Acetaminophen and myocardial stunning after transient ischemia in rabbit hearts.
AB  - BACKGROUND: Myocardial stunning is a lingering contractile dysfunction that
      occurs after brief ischemia, even in the absence of necrosis. Recent studies have
      shown that acetaminophen may have some benefit on the return of left ventricular
      function after brief global ischemia in an in vitro model. This study was
      conducted to determine whether treatment with acetaminophen results in enhanced
      myocardial tolerance to transient ischemia-reperfusion by improving left
      ventricular function and decreasing stunning in an in vivo model. METHODS:
      Anesthetized, open-chest rabbits were randomized to receive acetaminophen (37
      mg/kg, n = 13) or saline (n = 11) 15 minutes before a series of transient
      coronary artery occlusions followed by reperfusion (three 10-minute periods of
      ischemia with 5 minutes reperfusion between). Hemodynamics and maximal and
      minimal values of developed pressure velocity (dP/dt) were measured at baseline,
      during ischemia, and throughout 2 hours of reperfusion. To assess myocardial
      stunning, echocardiography was used to determine regional systolic wall
      thickening fractions and global indices of function such as LV cavity dimensions
      and ejection fraction. RESULTS: Hemodynamic variables, including left ventricular
      systolic pressure and positive and negative dP/dt, were similar in both groups
      throughout the study. Left ventricular end-diastolic pressure was significantly
      lower in the acetaminophen group during occlusion and early reperfusion. The
      repeated short periods of ischemia in the free wall of the heart caused
      myocardial stunning in both groups. During ischemia, contractile function in the
      free wall was severely reduced, and although it improved during reperfusion,
      dysfunction persisted in the postischemic free wall after 2 hours of reflow,
      recovering to less than 52% of preischemic values (P < .01). The degree of
      dysfunction was similar in both groups. During ischemia, the end-diastolic left
      ventricular cavity area increased from 1.14 +/- 0.05 cm2 at baseline to 1.33 +/-
      0.08 cm2 (P < .05) in controls, but had recovered after 2 hours of reflow. The
      end-diastolic area in acetaminophen-treated hearts increased from 1.13 +/- 0.08
      cm2 at baseline to 1.35 +/- 0.08 cm2 during ischemia and also recovered 2 hours
      later. No significant differences in LV cavity areas were noted between the
      groups. Acetaminophen had no effect on changes in ejection fraction, which
      decreased similarly in both groups during ischemia to approximately 75% of
      baseline values. Although ejection fraction improved, it remained depressed at
      the end of reflow in both groups. CONCLUSION: Data from this study show that in a
      rabbit model of myocardial stunning, acetaminophen has a neutral effect on
      hemodynamics, recovery of fractional thickening, and on indices of global
      recovery such as left ventricular cavity dimensions or ejection fraction. Thus in
      the setting of experimental myocardial stunning, treatment with acetaminophen was
      safe but not cardioprotective.

PMID- 15965565
TI  - Myocardial calcification as a rare cause of congestive heart failure: a case
      report.
AB  - Myocardial calcification is a manifestation of either metastatic or dystrophic
      calcium deposition in the myocardium. Dystrophic calcification of the myocardium
      is most commonly seen in long-term survivors of substantial myocardial
      infarctions. Current literature has reported only 3 cases of myocardial
      calcification with normal coronary arteries. We present a case of an 80-year-old
      woman with multiple admissions over a 5-year period for congestive heart failure.
      She was found to have a normal left ventricular ejection fraction and normal
      coronary arteries on left heart catheterization. A high resolution computed
      tomography (CT) study of the chest revealed extensive left ventricular myocardial
      calcifications, which were not present 4 years earlier on CT. The patient's
      history and clinical presentation revealed no etiologic factors for her calcified
      myocardium.

PMID- 15965566
TI  - Lipid-lowering therapy in patients with peripheral arterial disease.

PMID- 15965568
TI  - Antiarrhythmic action of beta-blockers: potential mechanisms.
AB  - Sympathetic nervous system overactivity has been linked to ventricular
      tachyarrhythmias and sudden death. It has been hypothesized that the extent and
      nature of the arrhythmogenic effect of sympathetic stimulation depends on the
      underlying myocardial substrate, the mechanism of the arrhythmia, and the
      integrated effects of sympathetic stimulation in the particular individual
      circumstance. Multiple direct and indirect mechanisms of adrenergic action on the
      heart may benefit from the known antiarrhythmic actions of beta-blocker therapy
      and other interventions that decrease sympathetic tone. The antiarrhythmic
      mechanism of beta-blockade (and possibly alpha-blockade) will depend on the
      specific mechanism of the individual arrhythmia and will differ for those
      arrhythmias caused by tachycardia and ischemia, those caused by reentry and
      promoted by decreased conduction velocity and shortened refractoriness, and those
      caused by early or delayed afterdepolarizations, usually in the context of
      prolonged action potential duration. Antagonism of cardiac adrenergic activity by
      beta-blockade in particular is the best-established drug therapy to prevent
      ventricular arrhythmias.

PMID- 15965569
TI  - Ventricular arrhythmias: antiadrenergic therapy for the patient with coronary
      artery disease.
AB  - Patients who have had a recent myocardial infarction (MI) are at high risk of
      ventricular arrhythmias that often cause sudden cardiac death. It is believed
      that sympathetic overactivity in the peri-infarction period may alter the
      electrophysiology and structure of the myocardium, thus placing these patients at
      risk of developing rhythm disturbances. A number of pharmacologic and
      nonpharmacologic therapies have been shown to reduce the risk of post-MI
      mortality, including sudden cardiac death. beta-Adrenergic blockers are
      recommended for all post-MI patients without contraindications because of
      overwhelming clinical evidence of their benefit in reducing mortality in this
      patient population. Recent clinical trials of implantable cardioverter
      defibrillators have provided compelling support that they are effective in both
      the primary and secondary prevention of sudden cardiac death. In addition,
      several studies have shown that combination therapy with beta-blockers and
      implantable cardioverter defibrillators have synergistic effects that optimize
      the benefits of both therapies.

PMID- 15965570
TI  - Beta-Adrenergic blockers as antiarrhythmic and antifibrillatory compounds: an
      overview.
AB  - Beta-Adrenergic blockers have a wide spectrum of action for controlling cardiac
      arrhythmias that is larger than initially thought. Data from the past several
      decades indicate that, as an antiarrhythmic class, beta-blockers remain among the
      very few pharmacologic agents that reduce the incidence of sudden cardiac death,
      prolong survival, and ameliorate symptoms caused by arrhythmias in patients with
      cardiac disease. As a class of compounds, beta-blockers have a fundamental
      pharmacologic property that attenuates the effects of competitive adrenergic
      receptors. However, the net clinical effects of the different beta-receptor
      blockers may vary quantitatively because of variations in associated intrinsic
      sympathomimetic agonism and in their intrinsic potency for binding to beta
      receptors. These individual compounds also differ in their selectivity for
      beta(1)- and beta(2)-receptors. Metoprolol is a beta(1)-selective blocker,
      whereas carvedilol is a nonselective beta(1)- and beta(2)-blocker, an
      antioxidant, and has a propensity to inhibit alpha(1)-receptors and endothelin.
      Evolving data from controlled and uncontrolled clinical trials suggest that there
      are clinically significant differences among this class of drugs. Recent evidence
      also suggests that the antiarrhythmic actions of certain beta-receptor blockers
      such as carvedilol and metoprolol extend beyond the ventricular tissue to
      encompass atrial cells and help maintain sinus rhythm in patients with atrial
      fibrillation, especially in combination with potent antifibrillatory agents such
      as amiodarone. This introduction provides a current perspective on these newer
      developments in the understanding of the antiarrhythmic and antifibrillatory
      actions of beta-blockers.

PMID- 15965571
TI  - Antiadrenergic therapy in the control of atrial fibrillation.
AB  - Atrial fibrillation (AF) in heart failure develops commonly in older individuals
      and its prevalence increases as heart failure severity progresses. Because of
      deteriorating hemodynamics, patients with heart failure are at increased risk for
      developing AF and, conversely, AF in heart failure patients is associated with
      adverse hemodynamic changes. AF is believed to increase the mortality risk in
      heart failure, which may be minimized by treatment that includes the control of
      ventricular rate, prevention of thrombotic events, and conversion to normal sinus
      rhythm. Clinical guidelines recommend amiodarone or dofetilide in heart failure
      patients, but these drugs have certain drawbacks, such as an increased risk for
      bradyarrhythmias with amiodarone and proarrhythmic reaction with dofetilide. Some
      but not all clinical trials have suggested that rate control should be the
      primary therapeutic goal in high-risk heart failure patients with AF and, if
      unsuccessful, followed by rhythm control. The former is effectively achieved with
      rate-lowering beta-blockers alone or in combination with digoxin. Recent studies
      evaluating the effects of combination carvedilol/digoxin therapy demonstrate
      synergistic effects between the two drugs. This combination therapy decreased
      heart failure symptoms, effectively reduced ventricular rate, and improved
      ventricular function to a greater extent compared with that produced by either
      drug alone. Although digoxin alone is an effective heart failure treatment, its
      use as a single rate-control therapy is often ineffective in heart failure
      patients with AF associated with rapid ventricular response. Carvedilol is
      effective, alone or in combination, with digoxin in such heart failure patients
      with AF, and has been shown to reduce mortality risk in patients with chronic
      heart failure during prolonged therapy.

PMID- 15965572
TI  - Drug and drug-device therapy in heart failure patients in the post-COMET and SCD
      HeFT era.
AB  - Reduced left ventricular ejection fraction and heart failure are the most
      important risk factors for sudden cardiac death. Recent trials have contributed
      to the knowledge base of critical therapies for the treatment of left ventricular
      systolic dysfunction and heart failure as it relates to arrhythmic and sudden
      cardiac death. Both pharmacologic and device therapies can reduce sudden cardiac
      death. The trials discussed in this paper have identified the pharmacologic and
      device interventions that are likely to improve the length and quality of life of
      the patient with left ventricular dysfunction and reduce the risk of sudden
      cardiac death. The mortality and anti-arrhythmic effects of angiotensin
      converting enzyme inhibitors and beta-blockers have been confirmed in large-scale
      controlled clinical heart failure trials. Recent trials have evaluated which
      agents are most effective and which patients will derive the most benefit from
      device therapy in terms of the reduction in the risk of sudden cardiac death and
      in the amelioration of heart failure. The recent data from the Carvedilol or
      Metoprolol European Trial (COMET) and the Sudden Cardiac Death in Heart Failure
      Trial (SCD-HeFT) are discussed as the latest in the series of landmark studies
      that have shaped the current approaches to treating patients with heart failure
      and that have altered the heart failure treatment paradigm.

PMID- 15965573
TI  - A review of carvedilol arrhythmia data in clinical trials.
AB  - beta-Blockers are currently being evaluated more intensively to define their role
      in clinical use as antiarrhythmic agents. beta-Adrenergic blockade has been
      studied in relation to atrial fibrillation, ventricular arrhythmias, and sudden
      death; however, it is apparent from a number of studies that not all beta
      blockers are equally effective. Randomized clinical trial data, both in heart
      failure and post-myocardial infarction (MI) patients, have shown differences in
      mortality benefits in addition to a variable effect on arrhythmias and sudden
      death. Carvedilol, a third-generation beta-blocker with proven clinical benefit
      in the management of heart failure and post-MI patients, has properties that may
      make it an effective antiarrhythmic agent. This paper reviews the current
      clinical arrhythmia data available for carvedilol from large-scale clinical
      trials and small studies. The trial evidence demonstrates that carvedilol therapy
      can be an effective adjunctive rate-control therapy in patients with atrial
      fibrillation, prevent mortality in patients with heart failure or post-MI with
      left ventricular dysfunction, with or without atrial fibrillation, and reduce its
      onset and the incidence of ventricular arrhythmia and sudden death.

PMID- 15965574
TI  - Concomitant pelvic organ prolapse surgery with TVT procedure.
AB  - The aim of this study is to evaluate the efficacy and feasibility of concomitant
      pelvic reconstructive surgery with tension-free vaginal tape (TVT) procedure to
      treat pelvic organ prolapse women with urodynamic stress incontinence (USI) or
      occult USI. Seventy-five women with pelvic organ prolapse and diagnosed as USI or
      occult USI were enrolled in this study. All patients with USI or occult USI
      underwent TVT treatment under general anesthesia, combined with transvaginal
      total hysterectomy (VTH), anterior-posterior colporrhaphy (APC), and/or right
      sacrospinous ligament suspension (SSS) reconstructive surgeries. The subjective
      assessment was evaluated by using a visual analog scale (VAS) score and a urinary
      symptomatic questionnaire. The objective assessment was carried out with a 1-h
      pad test, cough stress test, and urodynamic examination. Of the 75 patients, 35
      patients with grade III uterine prolapse underwent VTH and APC, 30 patients with
      grade IV uterine prolapse underwent VTH, SSS, and APC, and the other 10 patients
      who had previous hysterectomy with total vaginal vault prolapse underwent SSS and
      APC. The mean follow-up interval was 25 months (12-42 months). The mean
      hospitalization was 5.9 days and the mean catheterization time was 3.8 days. The
      subjective success rate for the treatment of urine incontinence was 88%, and the
      objective complete cure rate was 84%. The rate of postoperative complications
      with persistent urinary urgency, de novo detrusor overactivity, dysfunctional
      voiding, and tape erosion were 50, 8, 12, and 1.3%, respectively. There were no
      bladder perforations during the TVT procedure and no perioperative complications
      requiring conversion to laparotomy. Pelvic organ prolapse women with USI or
      occult USI can be treated by reconstructive surgeries combined with a TVT
      procedure to treat and prevent postoperative USI.

PMID- 15965575
TI  - Long-term chronic complications from Stamey endoscopic bladder neck suspension: a
      case series.
AB  - Purpose/objective Long-term complications from anti-incontinence surgical
      procedures are rarely reported. We report on delayed presentation of
      complications relating to the synthetic bolster placed for the Stamey bladder
      neck suspension. MATERIALS AND METHODS: Patients undergoing re-operative surgery
      following prior Stamey endoscopic bladder neck suspension were selected from a
      surgical database. Four women with lower urinary tract and/or vaginal symptoms
      following prior Stamey endoscopic bladder neck suspension were identified. All
      patients had undergone removal of the bolster material by a single surgeon (ESR)
      at re-operation. Preoperative, operative, and postoperative inpatient and
      outpatient records were reviewed. RESULTS: Patients presented with a variety of
      symptoms including urinary incontinence, recurrent cystitis, vaginitis, and
      urinary frequency at 9, 11, 11, and 12 years after Stamey bladder neck
      suspension. In addition, two patients presented with recurrent, intermittent
      bloody vaginal discharge and two patients complained of recurrent urinary tract
      infections and irritative voiding symptoms. All patients underwent transvaginal
      excision of the Dacron bolster. Three patients also underwent placement of an
      autologous pubovaginal sling for symptomatic recurrent stress urinary
      incontinence. At a mean follow-up of 30 months all four patients were improved.
      There was no recurrence of vaginal discharge or urinary tract infections.
      Irritative voiding symptoms resolved. CONCLUSIONS: Delayed complications from
      surgically implanted synthetic materials can present many years after initial
      implantation. The clinical findings are often subtle and require a high degree of
      suspicion. Vaginal discharge and irritative urinary symptoms in patients with
      even a remote history of Stamey bladder neck suspension should prompt a thorough
      vaginal exam and cystoscopy. Excision of the bolsters can be performed and is
      usually followed by symptomatic improvement.

PMID- 15965576
TI  - Transobturator tape erosion associated with leg pain.
AB  - A 39 year-old vaginal multipara status postpubovaginal sling in 2002 and a
      transobturator tape procedure in 2004 presented with persistent stress
      incontinence and vaginal polypropylene mesh erosion. Ten days later, she
      presented to the emergency room with severe right groin pain, difficulty walking,
      fever, and chills. She described shooting pain originating from the right
      inguinal ligament radiating down her right leg anteriorly. Although her
      neurologic examination was normal, palpation of the right obturator internus
      muscle reproduced her pain. MRI clearly revealed the course of the mesh tape
      through the obturator muscles and marked increase in the size of the right
      adductor and obturator internus muscles, apparently compressing the adjacent
      neurovascular fascicle. The patient was taken to the operating room where the
      polypropylene tape was easily removed through the vaginal erosion. Mesh cultures
      were positive for bacteroides fragilis. She experienced complete symptom
      resolution within 1 week of tape removal.

PMID- 15965577
TI  - Bladder wall abscess following midurethral sling procedure.
AB  - Midurethal sling procedures are gaining popularity as the treatment of choice for
      stress urinary incontinence. Complications that were described include bladder
      perforation, urinary retention, pelvic hematoma and suprapubic wound infection.
      Sling erosion and pelvic abscess are rare complications of midurethral slings. We
      report the first case of an abscess formed within the wall of the urinary
      bladder, 7 months following a midurethral sling procedure.

PMID- 15965578
TI  - Prosthetic repair, intestinal resection, and potentially contaminated areas: safe
      and feasible?

PMID- 15965579
TI  - Lipoma of the cord and round ligament: an overlooked diagnosis?
AB  - Lipoma of the cord, once considered rare and insignificant, has been cast in a
      new light by laparoscopic pre-peritoneal surgery, with diagnostic and therapeutic
      implications. This study aimed to determine the incidence, significance and
      association of spermatic cord lipomas to inguinal hernias. A retrospective review
      was performed for all hernia operations carried out between January 1999 and
      November 2002. The incidence of cord lipomas and their relation to inguinal
      hernias were evaluated. There were 123 repairs performed on 111 patients, 90 of
      which were laparoscopic via the pre-peritoneal approach, 29 were open and 4
      converted from laparoscopic to open in the early part of the series. All but two
      cases were male (neither female had associated lipoma of the round ligament).
      Twenty-six lipomas of the cord were identified with an incidence of 21%. Sixteen
      were associated with hernia and only 10 were pure cord lipoma, an incidence of
      8%. Thirteen repairs represented recurrent hernias, two of which had pure cord
      lipoma, one had an associated sac. Only two lipomas were suspected clinically
      prior to surgery. Lipoma of the cord is a poorly recognised entity that can be
      present with groin symptoms and clinical findings indistinguishable from inguinal
      hernia. Its incidence was poorly appreciated prior to the laparoscopic era.

PMID- 15965580
TI  - Different types of variant muscle nociception after intermittent and continuous
      neuromuscular stimulation in rats.
AB  - Critical assessment of experimental muscle-pain models resulting from maximal
      muscle contraction may provide a means of assessing hypersensitivity and the
      central nociceptive mechanisms involved in diffused muscle pain. The aim of the
      present study was, therefore, to investigate the patterns of nociceptive behavior
      and neuronal changes in the rat spinal cord after two modes of maximal muscle
      contraction. The gastrocnemius muscle of adult male Sprague-Dawley rats was
      subjected to continuous (10 min) or intermittent (60 min, 10/50 s on/off ratio)
      premodulated electrical stimulation of median frequency. Similar peak forces but
      different patterns of contraction output were generated by these two stimulation
      modes. Nociceptive behavioral scores and hind-leg oedema were significantly
      greater in the continuous group compared to the controls; however, significant
      difference was not demonstrated for either parameter comparing the intermittent
      and control groups. The sensory threshold was slightly reduced after the
      intermittent stimulation, and elevated after the continuous modality. The
      elevation of sensory threshold could be reversed by naloxone administration. More
      Fos-labeled nuclei were noted for both of the stimulation groups relative to the
      controls. The Fos-labeled nuclei were larger for the intermittent group than for
      the continuous and control analogs. The results of the present study suggest that
      prolonged contraction from continuous stimulation results in specific nociceptive
      neuron activation, muscle lesion and endogenous opioid release causing
      exaggerated nociception.

PMID- 15965581
TI  - Molecular genetics of unconjugated hyperbilirubinemia in Taiwanese.
AB  - In bilirubin metabolism, increased destruction of erythrocytes, defect in the
      function of organic anion transporter polypeptide 2 (OATP2) or UDP
      glucuronosyltransferase 1A1 (UGT1A1) may result in unconjugated
      hyperbilirubinemia. Although glucose-6-phosphate dehydrogenase (G6PD) deficiency
      is known to be associated with the development of neonatal hyperbilirubinemia, it
      was observed that in neonates severe hyperbilirubinemia caused by G6PD
      deficiency, without associated polymorphisms in the UGT1A1 or the OATP2 gene, was
      preventable. Variations at the nucleotide (nt) 388 of OATP2 gene and nt-211 of
      UGT1A1 gene, were found to be a risk factor for severe hyperbilirubinemia amongst
      Taiwanese neonates, respectively. G6PD deficiency, variations at nts 388 and 521
      of OATP2 gene, and variations at nt-211 and in the promoter area of UGT1A1 gene
      were reported to be the risk factors for the occurrence of mild
      hyperbilirubinemia amongst Taiwanese adults. The status of the haplotypes of
      G6PD, OATP2, and UGT1A1 genes affected the odds ratio and the bilirubin levels in
      the hyperbilirubinemic subjects. Moreover, carriage of the variant-211 UGT1A1
      allele, as well as UGT1A7*3 allele, was demonstrated to represent a risk factor
      for the development of, and a determinant for, metastases associated with
      Taiwanese colorectal-cancer patients. Further investigation is warranted to
      evaluate this phenomenon.

PMID- 15965582
TI  - Regional differences in the dynamics of refractoriness in intact and
      hypertrophied in situ canine hearts.
AB  - OBJECTIVES: Functional re-entry is thought to represent the predominant mechanism
      underlying ventricular arrhythmias. Functional conduction block may be caused by
      regional dispersion of refractoriness (ERP). Dispersion of ERP may not be evident
      at baseline, but may occur with sudden changes in heart rate, as ventricular
      arrhythmias are commonly induced by short-long-short cycles. METHODS: We examined
      the dynamics of local ERPs at two left ventricular (LV) sites in dogs with either
      no structural heart disease or biventricular hypertrophy (BVH). ERPs were
      determined at each of four bipoles of two adjacent needle electrodes in the LV
      apex and the lateral wall. The stimulation protocol included two different basic
      cycle lengths, one or two longer cycles after a train of 6 or 5 shorter cycles,
      and one shorter cycle after a train of 6 longer cycles. RESULTS: In normal dogs,
      a significant apicolateral ERP gradient was only evident with the longer basic
      cycle length. One shorter cycle was sufficient to dissolve that gradient. One
      longer cycle was enough to create a regional ERP gradient. Dynamic regional
      gradients occurred because the apex responded more markedly and more readily to
      abrupt changes in cycle length. BVH led to an increase in ERP at both LV sites
      and to an aggravation of regional ERP gradients. CONCLUSIONS: Dynamic ERP
      behavior seems to depend on topography and underlying pathology. Abrupt changes
      in heart rate might induce dynamic refractory gradients between various regions
      of the normal heart, but also between adjacent regions inhomogenously affected by
      hypertrophy.

PMID- 15965583
TI  - Remote postconditioning. Brief renal ischemia and reperfusion applied before
      coronary artery reperfusion reduces myocardial infarct size via endogenous
      activation of adenosine receptors.
AB  - OBJECTIVES: A series of brief coronary artery reperfusions and reocclusions
      applied during the early minutes of coronary artery reflow ("postconditioning")
      attenuates reperfusion injury. However, it is not known whether brief ischemia
      reperfusion applied to a distant organ at the onset of myocardial reperfusion
      (i.e. "remote postconditioning", remote PostC) reduces infarct size in the
      reperfused myocardium. In an in vivo anesthetized rat model of myocardial
      infarction induced by coronary artery occlusion and reperfusion, this study
      tested the hypothesis that remote postC induced by a single 5 minute episode of
      renal artery (RA) occlusion and reperfusion applied immediately before the onset
      of coronary artery reperfusion protects the myocardium from reperfusion injury by
      mechanisms involving endogenous adenosine receptor activation. METHODS: All rats
      were subjected to a total of 30 minutes of left coronary artery occlusion (LCAO)
      and 3 hours of reperfusion. The rats were randomized to one of six groups: 1)
      CONTROL: LCAO and reperfusion only with no other intervention; 2) Remote PostC:
      after 24 minutes of LCAO the RA was occluded for 5 minutes and released 1 min
      before coronary artery reperfusion; 3) Permanent RA occlusion: the RA was
      permanently occluded after 24 minutes LCAO continuing to the end of reperfusion;
      4) Delayed Remote PostC: after 26 minutes LCAO the RA was occluded for 5 minutes,
      and its release was delayed until 1 min after coronary artery reperfusion; 5) CON
      + SPT: rats with LCAO and reperfusion received 10 mg/kg IV of the non-selective
      adenosine receptor antagonist 8-sulfophenyl theophylline [SPT] administered 5
      minutes before coronary artery reperfusion; and 6) Remote PostC + SPT: after 24
      minutes of LCAO the RA was occluded for 5 minutes and released 1 minute before
      coronary artery reperfusion in the presence of 10 mg/kg SPT given 5 min before
      coronary artery reperfusion. RESULTS: Myocardial infarct size (percentage
      necrosis/area at risk, mean +/- SEM) was reduced by 50% in Remote PostC (25 +/-
      4%) compared to CONTROL (49 +/- 4%, p = 0.003), consistent with a reduction in
      plasma CK activity (44 +/- 5 vs. 67 +/- 6 U/ml, p = 0.023). In contrast,
      permanent RA occlusion before LCAO and reperfusion failed to reduce myocardial
      infarct size (47 +/- 5%) vs CONTROL. Delaying the release of the RA occlusion
      (delayed Remote PostC) abrogated the myocardial infarct reduction observed with
      Remote PostC (48 +/- 6%). SPT alone had no effect on infarct size (47 +/- 4% in
      CON + SPT vs. 49 +/- 4% in CON); however, Remote PostC+SPT abrogated the
      myocardial infarct size reduction in Remote PostC (50 +/- 3% in Remote PostC +
      SPT vs. 25 +/- 4% in Remote PostC). CONCLUSIONS: Remote renal postconditioning
      applied immediately before the onset of coronary artery reperfusion provides
      potent myocardial infarct size reduction likely exerted during the first minutes
      of coronary artery reperfusion. This inter-organ remote postconditioning
      phenomenon is likely mediated in part by release of adenosine by the ischemic
      reperfused kidney and subsequent activation of adenosine receptors.

PMID- 15965585
TI  - Impairment-oriented training and adaptive motor cortex reorganisation after
      stroke: a fTMS study.
AB  - In a sample of 28 subacute anterior circulation ischemic stroke patients with
      severe arm paresis, reduced motor cortex excitability (increased motor
      thresholds, reduced MEP amplitudes, reduced number of active points) and a
      reduced conduction velocity in the corticospinal system were found in the
      affected hemisphere. At the same time motor cortex topology for the abductor
      pollicis brevis (APB) representation was comparable for the affected and non
      affected hemisphere. Considerable arm motor recovery (Fugl-Meyer test) was
      observed when assessed four weeks later after a period of rehabilitation
      intervention. Motor cortex excitability and conduction velocity in the
      corticospinal system improved in the affected hemisphere. In addition, APB
      representation showed a medial shift in patients with such a representation at
      pre test (n=14). Multiple stepwise regression indicated that of all transcranial
      magnetic stimulation (TMS) parameters only the medial shift of the motor cortex
      map predicted motor recovery. Assessing the effect of training time (non
      intensified vs. intensified therapy) and type of arm training (Bobath approach
      vs. Arm BASIS training) with a randomised controlled design revealed that the
      impairment-oriented Arm BASIS training improved motor control more than the
      control conditions. In addition, patients of the group receiving the Arm BASIS
      training with an APB representation at pre test showed a medial shift of the
      motor cortex map and improved conduction times. In conclusion, changes in motor
      cortex topology were likely to be relevant for motor recovery and might have been
      induced by the impairment-oriented training.

PMID- 15965586
TI  - Pre-clinical diagnosis of Alzheimer disease combining platelet amyloid precursor
      protein ratio and rCBF spect analysis.
AB  - Platelet Amyloid Precursor Protein ratio of different abnormal forms and 99mTc
      ECD SPECT perfusion analysis were evaluated in Mild Cognitive Impairment (MCI)
      subjects who progressed to Alzheimer Disease (AD) and in stable MCI. We report
      that their combined evaluation increases the discriminative power of the analysis
      in identifying presymptomatic AD. The positive predictive value of these combined
      markers in identifying progressive MCI was 0.87, and the negative predictive
      value was 0.90. This observation suggests that the interplay of different markers
      should be considered for enhancing diagnostic accuracy of pre-clinical AD.

PMID- 15965587
TI  - Acute left hemispheric syndrome with cortical lesions in a patient with secondary
      porphyrinuria.

PMID- 15965588
TI  - Multimedia article. Laparoscopic management of median arcuate ligament syndrome.
AB  - Median arcuate ligament syndrome is a rare disorder resulting from luminal
      narrowing of the celiac artery by the insertion of the diaphragmatic muscle
      fibers or fibrous bands of the celiac nervous plexus. The syndrome is
      characterized by weight loss, postprandial abdominal pain, nausea, vomiting, and
      an epigastric bruit. Surgical management entails complete division of the median
      arcuate ligament. The video demonstrates the laparoscopic release of the median
      arcuate ligament in a patient with median arcuate ligament syndrome. The patient
      is a 22-year-old male with a 6-month history of epigastric abdominal pain,
      nausea, vomiting, a 140-lb. weight loss, and an epigastric bruit on physical
      exam. Aortography demonstrated a >or=90% extrinsic compression of the celiac
      artery. A full laparoscopic skeletonization of the celiac artery and branch
      vessels was performed. Intraoperative duplex U/S demonstrated flow rate reduction
      after the median arcuate ligament release. A postoperative CT angiogram
      demonstrated no residual stenosis. The patient was discharged on postoperative
      day 3 and remained asymptomatic after 7 months of follow-up. Laparoscopic release
      of the median arcuate ligament is a novel approach to the management of celiac
      artery compression syndrome. The role of minimally invasive techniques to manage
      median arcuate ligament syndrome is evolving but they appear to be a safe
      alternative to open surgery.

PMID- 15965590
TI  - Drug release from cast films of ethylene vinyl acetate (EVA) copolymer: Stability
      of drugs by 1H NMR and solid state 13C CP/MAS NMR.
AB  - The study utilizes an oral biocompatible material based on ethylene vinyl acetate
      copolymer (EVA) designed to release drugs in vitro at therapeutic levels over
      several days. We examined the drug stability during film casting process using
      proton and solid state NMR techniques. The drug-loaded EVA films were prepared
      from the dry sheet obtained by solvent (dichloromethane) evaporation of polymer
      casting solutions. Drugs tested include chlorhexidine diacetate (CDA),
      doxycycline hydrochloride (DOH), tetracycline hydrochloride (TTH) and nystatin
      (NST). Drug release from the films was examined for at least 14 days in 10 ml
      ddH2O (NST in water/ethanol (4:1)) which was replaced daily. Changes in optical
      density were followed spectraphotometrically. Effect of temperature on rate
      measurements was studied and the energies of activation (E*) were calculated
      using Arrhenius plots. Effect of EVA copolymer composition on CDA release rate
      was also investigated. The enhanced rates with temperature increase may be
      attributed to the formation of channels with increased geometry in the polymer.
      The highest E* observed for CDA compared to DOH and TTH may be related to their
      average molecular weights. Spectral analyses for CDA and NST revealed that the
      chemical and physical structures of the drugs remained unaffected during the film
      casting process.

PMID- 15965591
TI  - Effect of C content on the mechanical properties of solution treated as-cast ASTM
      F-75 alloys.
AB  - The mechanical properties of solution treated ASTM F-75 alloys with various
      carbon contents have been studied. Alloys cast under the same conditions were
      subjected to solution treatment for several periods and then their tensile
      properties were evaluated. In the as-cast conditions, the alloys exhibited higher
      strength values with increasing carbon content whereas their ductility was not
      significantly affected. For the solution treated alloys, the variation of the
      strength was characterized by a progressive increase for short treatment times
      until a maximum value was achieved, which was followed by a diminution in this
      property for longer treatment times. This behavior was more accentuated for the
      case of the alloys with medium carbon contents, which also exhibited the highest
      values of strength. Furthermore, the alloy's ductility was enhanced progressively
      with increasing solution treatment time. This improvement in ductility was
      significantly higher for the medium carbon alloys compared with the rest of the
      studied alloys. Thus, high and low carbon contents in solution treated ASTM F-75
      alloys did not produced sufficiently high tensile properties.

PMID- 15965592
TI  - Composite formation from hydroxyapatite with sodium and potassium salts of
      polyphosphazene.
AB  - The low temperature synthesis of composites potentially suitable as bone
      substitutes which form in vivo, was investigated. The composites were comprised
      of stoichiometric hydroxyapatite (SHAp) and water-soluble poly phosphazenes.
      These constituents were selected because of their biocompatibility, and were
      mixed as powders with a phosphate buffer solution (PBS) to form the composites.
      The effects of poly[bis(sodium carboxylatophenoxy)phosphazene] (Na-PCPP) or
      poly[bis(potassium carboxylatophenoxy) phosphazene] (K-PCPP) on stoichiometric
      hydroxyapatite (SHAp) formation from tetracalcium phosphate and anhydrous
      dicalcium phosphate were assessed. The kinetics and reaction chemistries of
      composite formation were followed by isothermal calorimetry, X-ray diffraction,
      infrared spectroscopy and scanning electron microscopy. In the presence of 1% by
      weight of polyphosphazenes, composites comprised of SHAp and calcium cross-linked
      polymer salts were formed. Thus a mechanism for binding between polymer chains
      was established. Elevated proportions (5 and 10% by weight) of polyphosphazene,
      however, resulted in the inhibition of SHAp formation. This is attributed to the
      formation of viscous polymer solution coatings on the calcium phosphate
      precursors, retarding their reaction, and consequently inhibiting SHAp formation.

PMID- 15965594
TI  - Microstructural analysis of implant-bone interface of hydroxyapatite-coated and
      uncoated Schanz screws.
AB  - The aim of the study was to compare the pin-bone interface microstructural
      characteristics of hydroxyapatite-coated (HAC) and stainless steel Schanz screws
      after 2, 4 and 6 months of implantation in a sheep model. The microstructure and
      composition of the hydroxyapatite coating were analyzed using scanning electron
      microscopy (SEM) and X-ray diffraction (XRD) analysis. Twelve coated and 12
      uncoated screws were implanted into both femora of three sheep, each sheep
      receiving eight screws. Specimens of polished bone with screws were examined with
      SEM and light microscope for morphometric analyses. The HAC was approx. 40 microm
      thick, the grain size ranged from 5 to 40 microm, with pores less than 20 microm.
      The atomic ratio of Ca/P was 1.62. SEM showed that the bone-implant contact was
      better with HAC than with uncoated implants. The ingrowth of the bone in the HAC
      was clearly seen. Morphometric analysis showed good bone-implant contact in 65.1
      (+/-24.6)% in the HAC and 32.0 (+/-23.3)% in the uncoated group (p<0.001).
      Although the percentage of good contact increased with time for both groups, it
      was significantly higher for HAC screws. Our investigation demonstrated a time
      dependent improvement of implant-bone contact of the HAC compared to standard
      stainless steel implants in the chosen experimental conditions.

PMID- 15965593
TI  - New biocomposite [biphasic calcium phosphate/ poly-DL-lactide-co
      glycolide/biostimulative agent] filler for reconstruction of bone tissue changed
      by osteoporosis.
AB  - Biphasic calcium phosphate-poly-DL-lactide-co-glycolide composite biomaterial
      with and without biostimulative agents (protein-rich plasma or fibrin) was
      synthesised in the form suitable for reconstruction of bone defects. The
      composite used as filler was obtained by precipitation in solvent-non-solvent
      systems. The material, calcium phosphate granules covered by polymer, was
      characterised by wide-angle X-ray structural analysis, scanning electron
      microscopy, infrared spectroscopy and differential scanning calorimetry.
      Reparation of bone tissue damaged by osteoporosis was investigated in vivo on
      rats. The method applied enabled production of granules of calcium phosphate-poly
      DL-lactide-co- glycolide composite biomaterial of average diameter 150-200 mum.
      Histological analysis confirmed recuperation of the alveolar bone, which
      osteoporosis-induced defects were repaired using composite biomaterial. By
      addition of biostimulative agents, intensity of osteogenesis increases
      accompanied by the formation of regular, new bone structure.

PMID- 15965595
TI  - Microstructures and bond strengths of plasma-sprayed hydroxyapatite coatings on
      porous titanium substrates.
AB  - Hydroxyapatite (HA) coating was carried out by plasma spraying on bulk Ti
      substrates and porous Ti substrates having a Young's modulus similar to that of
      human bone. The microstructures and bond strengths of HA coatings were
      investigated in this study. The HA coatings with thickness of 200-250 microm were
      free from cracks at interfaces between the coating and Ti substrates. XRD
      analysis revealed that the HA powder used for plasma spraying had a highly
      crystallized apatite structure, while the HA coating contained several phases
      other than HA. The bond strength between the HA coating and the Ti substrates
      evaluated by standard bonding test (ASTM C633-01) were strongly affected by the
      failure behavior of the HA coating. A mechanism to explain the failure is
      discussed in terms of surface roughness of the plasma-sprayed HA coatings on the
      bulk and porous Ti substrates.

PMID- 15965596
TI  - Development of a system to adsorb drugs onto calcium phosphate materials.
AB  - Several studies were carried out in order to reduce the systemic use of
      antibiotics due to the high concentration required to provide the minimum
      inhibitory concentration (MIC) at infected sites. The aim of this study was to
      develop a system of drug adsorption onto commercial hydroxyapatite (HA,
      Ca10(PO4)6(OH)2) and glass reinforced hydroxyapatite (GR-HA) granules. The drug
      will then be released for the local treatment of periodontitis. The antibiotics
      used in this study were metronidazole, a specific antibiotic indicated for the
      systemic treatment of periodontitis, and ampicillin, a wide spectrum antibiotic.
      UV spectroscopy was used to measure the amount of drug adsorbed onto HA and GR-HA
      granules. Results showed that metronidazole was unable to adsorb on the
      material's surface, as opposed to ampicillin which adsorbed both onto HA and GR
      HA. Preliminary release kinetics studies were carried out using a flow through
      dissolution system. Results are discussed in terms of the influence of the
      different surface characteristics of the materials on the adsorption processes.

PMID- 15965597
TI  - Control of surface morphology of carbide coating on Co-Cr-Mo implant alloy.
AB  - Wear of materials used in artificial joints is a common failure mode of
      artificial joints. A low wear rate for implants is believed to be critical for
      extending implant service time. We developed a carbide-coated Co-Cr-Mo implant
      alloy created in plasma of methane and hydrogen mixed gas by a microwave plasma
      assisted surface reaction. The carbide-coated Co-Cr-Mo has a unique "brain coral
      like" surface morphology and is much harder than uncoated Co-Cr-Mo. The effect of
      plasma processing time and temperature on the surface morphology of the top
      carbide layer was studied toward optimizing the surface coating. The ratios of
      average roughness, Ra, core roughness, Rk, and summation of core roughness,
      reduced peak height (Rpk) and reduced valley depth (Rvk), Rk+Rpk+Rvk, for the 6
      h/985 degrees C coating to those for the 0.5-h/985 degrees C coating were 1.9,
      1.7, and 1.9, respectively. The ratios of Ra, Rk, and Rk+Rpk+Rvk for the 4-h/1000
      degrees C coating to those for the 4-h/939 degrees C coating were 2.3, 2.3, and
      2.0, respectively. With the proper combination of plasma processing time and
      temperature, it may be possible to change the thickness of the peak-valley top
      cluster by fourfold from approximately 0.6 microm to approximately 2.5 microm.
      Finally, the growth mechanism of the carbide layers on Co-Cr-Mo was discussed in
      the context of atomic composition analysis.

PMID- 15965598
TI  - In vitro properties of PLLA screws and novel bioabsorbable implant with elastic
      nucleus to replace intervertebral disc.
AB  - The suitability of two different implant types for the replacement of the
      intervertebral disc was studied in vitro. Self-reinforced poly-L-lactide (SR
      PLLA) screws O 4.5 mm were studied 24 weeks in vitro and cylindrical implants
      with elastic nucleus made of poly(L/D)lactide 96/4, poly(L/DL)lactide 70/30,
      Bioactive Glass n:o 13-93 and Polyactive 1000PEOT70PBT30 were studied 15 weeks in
      vitro. The cylindrical implant mimics the size and shape of the intervertebral
      disc. During the in vitro, there were no changes in compression properties with
      either implant types. The screws had sufficient modulus for intervertebral
      ossification in the canine model and the cylindrical implant showed also
      sufficient mechanical properties. These results suggest that both implant types
      could be used in clinical testing.

PMID- 15965599
TI  - An experimental and finite element poroelastic creep response analysis of an
      intervertebral hydrogel disc model in axial compression.
AB  - A hydrogel intervertebral disc (IVD) model consisting of an inner nucleus core
      and an outer anulus ring was manufactured from 30 and 35% by weight Poly(vinyl
      alcohol) hydrogel (PVA-H) concentrations and subjected to axial compression in
      between saturated porous endplates at 200 N for 11 h, 30 min. Repeat experiments
      (n=4) on different samples (N=2) show good reproducibility of fluid loss and
      axial deformation. An axisymmetric nonlinear poroelastic finite element model
      with variable permeability was developed using commercial finite element software
      to compare axial deformation and predicted fluid loss with experimental data. The
      FE predictions indicate differential fluid loss similar to that of biological
      IVDs, with the nucleus losing more water than the anulus, and there is overall
      good agreement between experimental and finite element predicted fluid loss. The
      stress distribution pattern indicates important similarities with the biological
      IVD that includes stress transference from the nucleus to the anulus upon
      sustained loading and renders it suitable as a model that can be used in future
      studies to better understand the role of fluid and stress in biological IVDs.

PMID- 15965600
TI  - Response of primary fibroblasts and osteoblasts to plasma treated
      polyetheretherketone (PEEK) surfaces.
AB  - Polyetheretherketone (PEEK) is a synthetic polymer with suitable biomechanical
      and stable chemical properties, which make it attractive for use as an
      endoprothetic material and for ligamentous replacement. However, chemical surface
      inertness does not account for a good interfacial biocompatibility, and PEEK
      requires a surface modification prior to its application in vivo. In the course
      of this experimental study we analyzed the influence of plasma treatment of PEEK
      surfaces on the cell proliferation and differentiation of primary fibroblasts and
      osteoblasts. Further we examined the possibility of inducing microstructured cell
      growth on a surface with plasma-induced chemical micropatterning. We were able to
      demonstrate that the surface treatment of PEEK with a low-temperature plasma has
      significant effects on the proliferation of fibroblasts. Depending on the surface
      treatment, the proliferation rate can either be stimulated or suppressed. The
      behavior of the osteoblasts was examined by evaluating differentiation
      parameters. By detection of alkaline phosphatase, collagen I, and mineralized
      extracellular matrix as parameters for osteoblastic differentiation, the examined
      materials showed results comparable to commercially available polymer cell
      culture materials such as tissue culture polystyrene (TCPS). Further
      microstructured cell growth was produced successfully on micropatterned PEEK
      foils, which could be a future tool for bioartificial systems applying the
      methods of tissue engineering. These results show that chemically inert materials
      such as PEEK may be modified specifically through the methods of plasma
      technology in order to improve biocompatibility.

PMID- 15965601
TI  - Comparison of microstructural evolution in Ti-Mo-Zr-Fe and Ti-15Mo biocompatible
      alloys.
AB  - The microstructural evolution and attendant strengthening mechanisms in two
      biocompatible alloy systems, the binary Ti-15Mo and the quaternary Ti-13Mo-7Zr
      3Fe (TMZF), have been compared and contrasted in this paper. In the homogenized
      condition, while the Ti-15Mo alloy exhibited a single phase microstructure
      consisting of large beta grains, the TMZF alloy exhibited a microstructure
      consisting primarily of a beta matrix with grain boundary alpha precipitates and
      a low volume fraction of intra-granular alpha precipitates. On ageing the
      homogenized alloys at 600 degrees C for 4 h, both alloys exhibited the
      precipitation of refined scale secondary alpha precipitates homogeneously in the
      beta matrix. However, while the hardness of the TMZF alloy marginally increased,
      that of the Ti-15Mo alloy decreased substantially as a result of the ageing
      treatment. In order to understand this difference in the mechanical properties
      after ageing, TEM studies have been carried out on both alloys in the homogenized
      and homogenized plus aged conditions. The results indicate that the omega
      precipitates dissolve on ageing in case of the Ti-15Mo alloy, consequently
      leading to a substantial decrease in the hardness. In contrast, the omega
      precipitates do not dissolve on ageing in the TMZF alloy and the precipitation of
      the fine scale secondary alpha leads to increased hardness.

PMID- 15965602
TI  - Fabrication of thromboresistant multilayer thin film on plasma treated poly
      (vinyl chloride) surface.
AB  - Layer-by-layer deposited anticoagulant multilayer films were prepared on ammonia
      plasma treated poly (vinyl chloride) (PVC). Fourier transform infrared
      spectroscopy-attenuated total reflectance (FTIR-ATR) and contact angle results
      revealed the presence of -NH2 on the ammonia plasma treated PVC surfaces and the
      layer-by-layer self-assembly process. The stability of multilayer film was
      studied with the radio labeled method. The remainder bovine serum albumin (BSA)
      in cross-linked 5(heparin/BSA) multilayer films dipped in phosphate buffered
      saline (PBS, pH 7.4) was more than 90% in 40 days. The static platelet adhesion
      result indicated the anticoagulant multilayer films deposited on the plasma
      treated PVC reduced platelet adhesion drastically and no thrombus forming. The
      plasma recalcification time revealed that the multilayer modified surfaces
      greatly prolonged the plasma recalcification time. Such an easy processing and
      shape-independent method may have good potential for surface modification of
      cardiovascular devices.

PMID- 15965603
TI  - Using DNA shuffling to create novel infectious bronchitis virus S1 genes:
      implications for S1 gene recombination.
AB  - We employed the staggered extension process (StEP) to shuffle the S1 genes from
      four infectious bronchitis virus (IBV) strains representing four unique
      serotypes. Upon creating a shuffled S1 gene library, we randomly selected 25
      clones and analyzed them by DNA sequencing. In total, eleven clones contained
      novel S1 gene recombinants. Based on sequence data, each recombinant was unique
      and contained a full-length open reading frame. The average number of crossovers
      per recombinant was 5 and the average number of point mutations was 1.3, leading
      mostly to non-synonymous amino acid changes. No recombinant contained sequences
      from all four parental genes and no recombinant contained any sequence from the
      distantly related Delaware 072 strain. Our data suggests that recombination
      between distantly related IBV strains within the S1 gene probably does not
      readily occur. This finding is extremely important in light of the common
      industry vaccination practice of mixing different live-attenuated IBV strains.

PMID- 15965604
TI  - Molecular characterization of virulent Newcastle disease virus isolates from
      chickens during the 1998 NDV outbreak in Kazakhstan.
AB  - Newcastle disease virus (NDV) infects domesticated and wild birds throughout the
      world and has the possibility to cause outbreaks in chicken flocks in future. To
      assess the evolutionary characteristics of 10 NDV strains isolated from chickens
      in Kazakhstan during 1998 we investigated the phylogenetic relationships among
      these viruses and viruses described previously. For genotyping, fusion (F) gene
      phylogenetic analysis (nucleotide number 47-421) was performed using sequences of
      Kazakhstanian isolates as compared to sequences of selected NDV strains from
      GenBank. Phylogenetic analysis showed that all newly characterized strains
      belonged to the genetic group designated as VIIb. All strains possessed a
      virulent fusion cleavage site (RRQRR/F) belonging to velogenic or mesogenic
      pathotypes with intracerebral pathogenicity indexes (ICPI) varying from 1.05 to
      1.87.

PMID- 15965605
TI  - Genome prediction of putative genome-linked viral protein (VPg) of astroviruses.
AB  - Positive-sense single-stranded RNA (+ssRNA) viruses replicate by uncoating the
      RNA genome for translation to provide viral proteins essential for genome
      replication and the production of new viral particles. The viral proteins are
      synthesized from a polyprotein precursor, which is cleaved nascently. The
      synthesized proteins include viral RNA-dependent RNA polymerase (RdRP), viral
      genome-linked protein (VPg), and a helicase. VPg is covalently attached to the
      genomic form of +ssRNA viruses. Helicases and NTPase unwind the RNA before
      replication. VPg and helicases have been identified in +ssRNA families, however,
      the presence of VPg and helicase in the Astroviridae, another +ssRNA family, has
      not been fully elucidated. Computational tools were utilized to provide sequence
      analysis evidence for the presence and genomic location of astrovirus VPg and
      helicase. HMMER program v2.1.1 was used to build Hidden Markov Model (HMM)
      profile for calicivirus VPg to search for conserved motifs in the astrovirus
      genome. We performed phylogenetic analysis of two genomic regions of astroviruses
      and caliciviruses (encoding the RdRP and VPg). We identified a putative VPg
      coding region in astrovirus. This region was located in open reading frame 1a
      (ORF1 a) and included sites with high sequence similarity to the VPg coding
      regions of Caliciviridae, Piconaviridae, and Potyviridae. A region encoding a
      putative astrovirus helicase identified conserved motifs only with pestivirus
      helicase sequences. Sequence analysis and comparison to other +ssRNA viruses
      supports the presence of VPg in the Astroviridae. Further laboratory analysis
      will be necessary to confirm these findings.

PMID- 15965606
TI  - Genome sequences and structures of two biologically distinct strains of Grapevine
      leafroll-associated virus 2 and sequence analysis.
AB  - Grapevine leafroll-associated virus 2 (GLRaV-2), a member of the genus
      Closterovirus within Closteroviridae, is implicated in several important diseases
      of grapevines including "leafroll", "graft-incompatibility", and "quick decline"
      worldwide. Several GLRaV-2 isolates have been detected from different grapevine
      genotypes. However, the genomes of these isolates were not sequenced or only
      partially sequenced. Consequently, the relationship of these viral isolates at
      the molecular level has not been determined. Here, we group the various GLRaV-2
      isolates into four strains based on their coat protein gene sequences. We show
      that isolates "PN" (originated from Vitis vinifera cv. "Pinot noir"), "Sem" (from
      V. vinifera cv. "Semillon") and "94/970" (from V. vinifera cv. "Muscat of
      Alexandria") belong to the same strain, "93/955" (from hybrid "LN-33") and "H4"
      (from V. rupestris "St. George") each represents a distinct strain, while
      Grapevine rootstock stem lesion-associated virus.

PMID- 15965607
TI  - Molecular characterization of a distinct begomovirus species and its associated
      satellite DNA isolated from Malvastrum coromandelianum in China.
AB  - A virus isolate Y160 was obtained from Malvastrum coromandelianum showing yellow
      vein symptoms in Baoshan, Yunnan province of China. The complete nucleotide
      sequence of DNA-A was determined, it contains 2747 nucleotides and has typical
      genomic organization of a begomovirus. Comparisons show that the total DNA-A of
      Y160 has the highest sequence identity (82.2%) with that of Malvastrum yellow
      vein virus-[Y47] (AJ457824), while less than 77.6% identities are found when
      compared with the other begomoviruses. The molecular data show that Y160 is a
      distinct begomovirus species, for which the name Malvastrum yellow vein Yunnan
      virus (MYVYNV) is proposed. Satellite DNA molecule (Y160beta) was found to be
      associated with Y160 using the abutting primers beta 0l and beta 02 specific for
      DNA beta. Y160beta consists of 1350 nucleotides, with a functional ORF (beta C1)
      in complementary-sense DNA. Y160beta has the highest sequence identity (73.5%)
      with DNA beta molecule associated with Malvastrum yellow vein virus-[Y47]
      (AJ421482).

PMID- 15965608
TI  - Apoptin induces chromatin condensation in normal cells.
AB  - Apoptin, a chicken anemia virus protein, was reported to induce tumor specific
      apoptosis, which was correlated with the nuclear localization of the protein in
      tumor cells. While in normal human cells, Apoptin was detected mainly in the
      cytoplasm and did not induce apoptosis. Using a recombinant adenovirus expressing
      Apoptin, we have found that Apoptin induced G(2)-M cell cycle arrest and
      chromatin condensation in cancer cells. Here we report that adenovirus mediated
      Apoptin expression also induces G(2)-M arrest in normal cells. In normal cells
      Apoptin is localized mainly in the cytoplasm but is also found in the nucleus of
      a subset of cells. Apoptin induces chromatin condensation not only when it is
      expressed in the nucleus but also when it is expressed in the cytoplasm. Our
      results indicate that Apoptin-induced chromatin condensation in the normal cells
      may not correlate with its nuclear localization and the mechanism of regulating
      the G(2)-M transition might be a target for Apoptin.

PMID- 15965609
TI  - Sequence divergence of four soilborne sugarbeet-infecting viruses.
AB  - Soilborne viruses are among the most harmful pathogens of sugarbeet (Beta
      vulgaris L.ssp. vulgaris) but most of them lack information on genetic
      variability due to paucity of sequence data. Only one isolate of Beet soil borne
      virus (BSBV; genus Pomovirus), Beet virus Q (BVQ; genus Pomovirus) and Beet soil
      borne mosaic virus (BSBMV; genus Benyvirus) has been characterised for the coat
      protein (CP) gene. In this study, the CP gene sequences of three isolates each of
      BSBV and Beet necrotic yellow vein virus (BNYVV; genus Benyvirus) (France,
      Germany and USA), two isolates of BVQ (France and Germany), and one isolate of
      BSBMV (USA) were determined. Phylogenetic analyses including sequences from
      databanks indicated that the French BNYVV isolate of this study belongs to so
      called P-type, the American isolate to A-type and the German isolate to B-type.
      The CP genes of the three BSBV isolates characterised in this study and the one
      available from databank were highly identical (98.4-99.0% at nucleotide level;
      one variable amino acid). The BSBMV isolate studied here differed from the
      previously characterised isolate for five nucleotides and four amino acids in the
      CP region. The two BVQ isolates characterised in this study contained three
      additional nucleotides resulting in an additional amino acid residue (arginine)
      at CP position 86, as compared to the only isolate available in databank.

PMID- 15965610
TI  - Loss of linkage disequilibrium and accelerated protein divergence in duplicated
      cytomegalovirus chemokine genes.
AB  - Human CMV (hCMV) encodes several captured chemokine ligand and chemokine receptor
      genes that may play a role in immune evasion. The adjacent viral alpha-chemokine
      genes UL146 and UL147 appear to have duplicated subsequent to a recent gene
      capture event. Sequence data from multiple hCMV isolates suggest accelerated
      protein evolution in one of the paralogues, UL146. Extensive sequence variation
      was noted throughout the more rapidly evolving paralogue, although significant
      variation was also observed within the more slowly evolving gene, especially
      within a region corresponding to a possible signal peptide. In contrast to the
      haplotype structure observed for other hCMV genes, the distribution of nucleotide
      variants indicates a marked loss of linkage disequilibrium within UL146 and to a
      lesser extent UL147. Despite evidence of accelerated protein evolution, the rate
      of nonsynonymous to synonymous substitutions (d(N)/d(S)) in the more rapidly
      evolving paralogue was not indicative of neutral evolution, but of moderate
      purifying selection. The data presented here provides a unique opportunity to
      study the mechanisms by which a recently duplicated pair of genes has diverged
      and suggests a role for recombination.

PMID- 15965611
TI  - Characterization of a very virulent Marek's disease virus mutant expressing the
      pp38 protein from the serotype 1 vaccine strain CVI988/Rispens.
AB  - Marek's disease virus (MDV), a highly cell-associated oncogenic chicken
      herpesvirus, causes Marek's disease in domestic chickens. A unique phosphoprotein
      of MDV, pp38, has previously been associated with the maintenance of
      transformation in MDV-induced tumor cell lines. However, recently, the biological
      properties of a deletion mutant virus (rMd5Deltapp38) revealed that pp38 is
      involved in early cytolytic infection in lymphocytes but not in the induction of
      tumors. Thus, pp38 is important for early cytolytic infection and not for
      transformation. The pp38 protein of the MDV serotype 1 vaccine strain
      CVI988/Rispens differs by one amino acid when compared to the pathogenic strains
      of MDV. Monoclonal antibody, H19, recognizes all serotype 1 MDV strains except
      CVI988/Rispens. Previous studies have also shown that the unique pp38 epitope in
      CVI988/Rispens induced high antibody response. In order to study the role of this
      epitope in the protective properties of CVI988/Rispens, we generated a mutant
      rMd5 virus in which the wild type pp38 gene has been substituted with that of
      CVI988/Rispens (rMd5/pp38CVI). The replication properties of rMd5/pp38CVI, both
      in vitro and in vivo, and tumor induction were examined. We found that the
      biological properties of rMd5/pp38CVI were similar to the wild type rMd5 virus
      with regards to in vivo replication, antibody response and tumor induction. This
      shows that the pp38 derived from CVI988/Rispens is not involved in protective
      properties as was previously suggested.

PMID- 15965612
TI  - Identification of a novel B cell epitope on the nucleocapsid protein of porcine
      reproductive and respiratory syndrome virus by phage display.
AB  - A phage display peptide library targeting the nucleocapsid (N) protein of porcine
      reproductive and respiratory syndrome virus (PRRSV) strain CH-1a was generated
      and used for epitope mapping. After 3 rounds of biopanning with the monoclonal
      antibody (MAb) N3H2 directed against the N protein, 3 positive phages were
      screened and sequenced. These phages share a consensus sequence, IQTAFNQGA, which
      corresponds to the amino acid (AA) 79-87 segment of the CH-1a N protein. A small
      DNA fragment coding for IQTAFNQGA was expressed as a fusion product, and reacted
      to N3H2 in Western blots and indirect ELISA. Four truncated peptides (IQTAFNQG,
      IQTAFNQ, QTAFNQGA, and TAFNQGA) expressed as GST fusion products failed to react
      with N3H2. The sequences around the N3H2-binding site among the N proteins of 57
      PRRSV strains were compared. Our results indicate that the IQTAFNQGA motif is
      highly conserved among North American and European isolates. We concluded that
      the precisely defined nona-peptide epitope is a novel conserved Linear B cell
      epitope on the N protein of PRRSV.

PMID- 15965613
TI  - Limited inter- and intra-patient sequence diversity of the genetic lineage A
      human metapneumovirus fusion gene.
AB  - Human metapneumovirus (hMPV) is associated with respiratory tract illness
      especially in young children. Two hMPV genetic lineages, A and B, and four
      sublineages A1, A2 and B1, B2 have been defined. Infection with hMPV occurs
      through membrane fusion mediated by the hMPV fusion (F) protein. In this study,
      the inter- and intra-patient genetic diversity of the lineage A hMPV F gene was
      investigated. Ten isolates were collected from 10 hMPV infected children. Viral
      RNA was isolated and amplified, and approximately 10 clones from each isolate
      were sequenced. Altogether 108 clones were successfully sequenced. The average
      interpatient sequence diversity was 1.68% and 1.64% at nucleotide and amino acid
      levels, respectively. The samples were divisible into two groups on the basis of
      intrapatient sequence diversity. In group 1 (4 children) the intra-patient
      sequence diversity was low (nt: 0.26-0.39%, aa: 0.51-0.94%) whereas group 2 (6
      children) had a higher intra-patient sequence diversity (nt: 0.85-1.98%, aa: 1.08
      2.22%). Phylogenetic analyses showed that the group 1 children harboured
      sublineage Al only, but interestingly group 2 children harboured both sublineages
      Al and A2, indicating they had been infected with at least two viruses. Several
      independent viruses contained premature stop codons in exactly identical
      positions resulting in truncated fusion proteins. Possibly this is a mechanism
      for immune system evasion. The F protein is a major antigenic determinant, and
      the limited sequence diversity observed lay emphasis on the hMPV F gene as a
      putative target for future vaccine development.

PMID- 15965614
TI  - Phylogenetic characteristics, genomic heterogeneity and symptomatic variation of
      five closely related Japanese strains of Potato virus X.
AB  - To elucidate the genomic determinants of Potato virus X (PVX) strains, which
      cause diverse responses in host plants, we determined the complete genomic RNA
      sequences of four Japanese PVX strains: PVX-BS, -BH, -OG, and -TO. These four
      strains, plus the previously sequenced PVX-OS strain, differ in their
      pathogenicity in wild potato (Solanum demissum) and tobacco (Nicotiana tabacum
      cv. Samsun NN). The genomic sequences of these five PVX strains were highly
      homologous (i.e., the nucleotide sequence identity ranged from 95.4 to 98.5%).
      Phylogenetic analysis indicated that the Japanese PVX strains originated from an
      ancestral PVX strain in the European group, and that the virulence of these
      strains in both S. demissum and tobacco is not correlated with their phylogenetic
      relationships, suggesting that the pathogenicity of each strain in these host
      plants is determined by a relatively small number of nucleotides and can easily
      be altered independent of phylogenetic relationships. Particularly, OS, BH, and
      BS, which respectively produce markedly contrasting ringspot, mosaic, and
      asymptomatic infections in tobacco leaves, were the most closely related,
      suggesting that these three strains are an attractive model for analyzing the
      genetic determinants causing these symptoms. A possible correlation between the
      genomic and biological differences of these strains is discussed.

PMID- 15965615
TI  - Mutation hot spots in the canine herpesvirus thymidine kinase gene.
AB  - The guanine and cytosine content (GC-content) of alpha-herpesvirus genes are
      highly variable despite similar genome structures. It is known that drug
      resistant HSV, which has the genome with a high GC-content (approximately 70%),
      commonly includes frameshift mutations in homopolymer stretches of guanine (G)
      and cytosine (C) within the thymidine kinase (TK) gene. However, whether such
      mutation hotspots exist in the TK gene of canine herpesvirus (CHV) which has a
      low GC-content was unknown. In this study, we investigated mutations in the TK
      gene of CHV. CHV was passaged in the presence of iodo-deoxyuridine (IDU), and IDU
      resistant clones were isolated. In all IDU-resistant virus clones, mutations in
      the TK gene were observed. The majority of these mutations were frameshift
      mutations of an adenine (A) insertion or deletion within either of 2 stretches of
      eight A's in the TK gene. It was demonstrated that CHV TK mutations frequently
      occur at a limited number of hot spots within long homopolymer nucleotide
      stretches.

PMID- 15965616
TI  - The molecular mechanism of human resistance to HIV-1 infection in persistently
      infected individuals--a review, hypothesis and implications.
AB  - Resistance to HIV-1 infection in Europeans is associated with a mutation in the
      gene that codes for the CCR5 protein that is present in Th2 cells and serves as a
      coreceptor for HIV-1 R5 strain. A deletion of 32 amino acids from the cytokine
      receptor prevents infection. This mutation prevails in Europeans and is absent in
      Africans. However, duplication of a gene that codes for a chemokine that binds to
      the CCR5 was discovered in Africans (mean gene copy 6 while in non-Africans the
      mean gene copy is 3). Higher expression of these genes protects T cells against
      HIV-1 infection in vitro. It should be noted that resistance to HIV-1 R5 variant
      does not protect against HIV-1 R4 variant. It was reported that a minority of
      highly HIV-1 exposed African professional sex workers (APSW) were resistant to
      the virus infection during a 10 years period. Recently, the analysis of the
      cytokines in the serum of the persistently infected seronegative women revealed
      that the latter hypo-expresses the cytokine IL-4. Since the molecular events
      during HIV-1 infection are associated with a marked increase in the levels of IL
      4 and IgE in the sera of the infected individuals, it suggests that AIDS is an
      allergy. Thus, a very low level of IL-4 production may abrogate the virus
      infection. Studies on the human IL-4 gene revealed that together with the IL-4
      mRNA a spliced variant with a deletion of exon 2 is synthesized. The latter is a
      natural antagonist of IL-4 and when expressed in an individual at a level higher
      than IL-4, the person will resist a microbial infection (e.g. Mycobacterium
      tuberculosis) or asthma. The present hypothesis suggests that the HIV-1 resistant
      APSWs produce more IL-4 delta 2 molecules than IL-4 molecules. The binding of IL
      4 delta 2 to IL-4 receptors on T and B cells prevents their functions and the
      infection by HIV-1. The implications of these studies are that treatment of HIV-1
      infected people with drugs that will block the IL-4 receptors will stop HIV-1
      infections and the determination of the levels of IL-4 and IL-4 delta 2 in the
      sera of HIV-1+ patients will enable to identify the individuals that have a
      natural resistance to HIV-l/AIDS and those who need treatments.

PMID- 15965617
TI  - The expanding role of MCH epidemiologists: evolving job description, tasks and
      skill areas, and sources of training support.

PMID- 15965618
TI  - Clustering of U.S. women receiving no prenatal care: differences in pregnancy
      outcomes and implications for targeting interventions.
AB  - OBJECTIVES: Prenatal care is an established mechanism for identifying and
      managing risk factors impacting pregnancy outcomes. Despite aggressive efforts in
      the United States (US) to assure that all women begin care in the first
      trimester, every year about 70,000 women in the US receive no care prior to
      delivery. We hypothesized that US women receiving no prenatal care comprise
      clusters (subgroups) with distinctive behavioral, socio-demographic, and medical
      risks and that birth outcomes differ among the clusters. METHODS: White, Black,
      and Hispanic women (n = 126,220) receiving no prenatal care and delivering a
      live, singleton infant were identified from linked birth and death certificates
      for years 1995 through 1997. Cluster analysis was used to group women with
      similar characteristics, and cluster assignment was evaluated using discriminant
      analysis. Birth outcomes for any care and no-care women were then examined using
      logistic regression. RESULTS: Six replicable clusters of women with no care were
      identified. Birth outcomes varied significantly among clusters and were two to
      four times worse for no-care clusters compared to outcomes for women receiving
      any care. CONCLUSIONS: Cluster analysis is an effective alternative for grouping
      individuals for use in public health education, intervention, and outreach
      programming. Women receiving no prenatal care were characteristically different
      from women receiving any care in this study, but they did not represent a
      homogenous group. Findings suggest that interventions should target reducing the
      proportion of women receiving no care and should be tailored to specific no-care
      clusters.

PMID- 15965620
TI  - Timing of enhanced prenatal care and birth outcomes in New Jersey's HealthStart
      program.
AB  - OBJECTIVE: This study examined the effects of prenatal care and the timing of its
      initiation on birth weight and gestational age outcomes among women in a state
      wide Medicaid enhanced prenatal care program. METHODS: Ordinary Least Squares and
      logistic regression analyses were performed using data on 88,196 births in New
      Jersey between 1988 and 1996. A large number of potentially confounding factors
      were included. RESULTS: Initiating prenatal care in the first trimester was
      associated with a 56 g advantage in birth weight (p = .01) compared to no care.
      Initiating prenatal care in the first or second trimester was associated with a 1
      day advantage in gestational age (p = .05). There were no significant effects of
      prenatal care, initiated in any trimester, on low-birth weight. Initiating care
      in the first versus the second trimester had no effect on the probability of
      delivering preterm. The findings did not vary by sociodemographic subgroup.
      CONCLUSION: This study provides support for claims that there is little that
      prenatal care can do to improve aggregate birth outcomes because most pregnancy
      complications are the result of behaviors and life circumstances that precede the
      pregnancy and are very difficult to reverse. Prenatal care, even with enhanced
      services, appears to offer too little, too late.

PMID- 15965619
TI  - Health promotion and psychosocial services and women's assessments of
      interpersonal prenatal care in Medicaid managed care.
AB  - OBJECTIVES: If prenatal health promotion and psychosocial support services are to
      remain accessible to Medicaid eligible women, evidence is needed as to whether
      the services improve care and benefit women in ways that matter to health plans.
      The aims of this study are to determine whether prenatal health promotion and
      psychosocial services are associated with better interpersonal care and greater
      satisfaction with care; and whether the effects on interpersonal care help
      explain satisfaction with care. RESEARCH DESIGN: A telephone survey of 363
      African American, Latina (US and nonUS-born) and White women receiving prenatal
      care in four Medicaid public health plans in California in 2001. Multivariate
      regression analyses were done with adjustments for potentially confounding
      variables. MEASURES: Independent variables included dichotomous variables for
      health promotion advice (five separate areas) and composite scales for
      psychosocial assessment (six areas combined). Dependent variables included
      satisfaction with care, and indices for interpersonal care (communication,
      decision-making, and interpersonal style). RESULTS: Women who report receiving
      health promotion or psychosocial services also report receiving better
      interpersonal care and rate their satisfaction with care higher. Receiving either
      type of support service is associated with higher quality communication, decision
      making and interpersonal style. The effects of the support services on
      satisfaction are, in turn, explained by the effects on interpersonal care.
      CONCLUSIONS: Prenatal health promotion and psychosocial services have associated
      benefits to enrollees that should matter to Medicaid health plans and their
      providers.

PMID- 15965621
TI  - Paternal influences on the timing of prenatal care among Hispanics.
AB  - OBJECTIVES: The purpose of this study was to examine the independent role of
      paternal influences on the onset of prenatal care among Hispanic women. METHODS:
      A total of 300 pregnant Hispanic women seeking prenatal care on or before their
      35th week of gestation were surveyed about their and their partner's pregnancy
      intention. Women in this study were recruited from clinics providing services to
      low income and medically indigent women. RESULTS: Father's pregnancy intention
      had a protective effect on the timely onset of prenatal care. Pregnancies that
      were unintended by the mother but were intended by the father had a lower
      likelihood of delayed care, as compared to those unintended by both (Odds Ratio
      [OR] = .54, 95% confidence interval [CI] = .28, .99). This trend was stronger
      among married than non-married couples. CONCLUSION: Comprehensive efforts are
      needed to involve male partners in family planning as well as in programs aimed
      at expanding adequate pre- and postnatal behaviors within Hispanics.

PMID- 15965622
TI  - Health departments do it better: prenatal care site and prone infant sleep
      position.
AB  - OBJECTIVES: Reduction of prone infant sleep position has been the main public
      health effort to reduce the incidence of Sudden Infant Death Syndrome (SIDS).
      METHODS: Oregon Pregnancy Risk Assessment Monitoring System (PRAMS) surveys a
      stratified random sample of women after a live birth. In 1998-1999, 1867 women
      completed the survey (64.0% unweighted response; 73.5% weighted response).
      RESULTS: Overall, 9.2% of all women "usually" chose prone infant sleep position,
      while 24.2% chose side and 66.5% chose supine position. Women receiving care from
      private physicians or HMOs more often chose prone position (10.6%) than women
      receiving prenatal care from health department clinics (2.5%), hospital clinics
      (6.1%) or other sites (8.3%). Compared to health department prenatal clinic
      patients, private prenatal patients were more likely to choose prone infant sleep
      position, adjusted odds ratio = 4.78 (95% confidence interval [CI] 1.64-13.92).
      CONCLUSIONS: Health Department clinics have done a better job than private
      physicians in educating mothers about putting infants to sleep on their backs.
      Providers-especially private providers-should continue to stress the importance
      of supine sleep position for infants.

PMID- 15965623
TI  - Seatbelt use during pregnancy: a comparison of women in two prenatal care
      settings.
AB  - OBJECTIVES: This study examines knowledge of proper automobile restraint use
      during pregnancy and attitudes toward restraint use. This manuscript, the second
      in a series, compares knowledge and attitudes in two populations of pregnant
      women, those receiving prenatal care at several county clinics and those
      receiving care in a private practice. METHODS: A survey requesting demographic
      information and frequency and knowledge of proper automobile restraint use was
      administered during prenatal visits. RESULTS: County clinic patients (n = 450,
      70% black) were younger and less educated than private practice patients (n =
      203, 75% non-Hispanic white). Fewer county patients (49%) always wore seatbelts
      prior to the pregnancy than private practice patients (88%). Correct use was
      reported by fewer county clinic patients (67%) than private practice patients
      (83%). Few (25-28%) in either setting reported receiving information on seatbelt
      use. CONCLUSIONS: Despite existing knowledge with respect to the consequences of
      seatbelt non-use in pregnant women, the proportion of women receiving information
      about correct seatbelt use during pregnancy appears to be low, regardless of care
      source.

PMID- 15965624
TI  - The UTAH VBAC Study.
AB  - BACKGROUND: In July 1999, The American College of Obstetricians and Gynecologists
      (ACOG) issued Practice Guideline number 5 on vaginal birth after cesarean section
      (VBAC) and trial of labor (TOL). This updated guideline recommends that a
      physician be immediately available during a TOL in the rare case of
      complications. We examined the effect this new guideline would have on
      physician's VBAC/TOL practices in Utah. OBJECTIVE: 1) Explore physician knowledge
      of ACOG Practice Guideline number 5; 2) Evaluate change in physician's VBAC
      practices in the previous 12 months; 3) Evaluate physician's ability to comply
      with ACOG Practice Guideline number 5 recommendations by rural, suburban, and
      urban location. METHODS: In spring 2001, we surveyed by mail all physicians
      practicing obstetrics in Utah. Questions included demographics, hospital data,
      VBAC/TOL practice patterns and awareness of ACOG Practice Guideline number 5.
      Physicians were classified as urban, suburban, or rural by their primary delivery
      hospital. RESULTS: We found 97% of obstetricians and 79% of family physicians
      were aware of ACOG Practice Guideline number 5. Forty-five percent of all
      physicians reported a decline in VBAC practices in the preceding 12 months. Urban
      physicians' use of VBAC/TOL decreased the least, followed by rural and suburban.
      Eighty-seven percent of physicians had C/S "immediately" available during TOL:
      urban physicians 100%, suburban 88%, and rural physicians 76%. Emergency C/S
      delivery was performed fastest at urban hospitals, slower at suburban, and
      slowest at rural hospitals. CONCLUSION: Physicians use of VBAC/TOL has changed.
      TOL is offered less by obstetrical providers in Utah and more repeat C/S are
      performed since 1999 when ACOG updated this policy guideline. This decline has
      been more noticeable in suburban and rural hospitals and is consistent with
      recent national trends. Many rural physicians are unable to comply with ACOG
      Practice Guideline number 5 recommendations.

PMID- 15965625
TI  - Omega-3 for baby and me: material development for a WIC intervention to increase
      DHA intake during pregnancy.
AB  - OBJECTIVE: The purpose of this project was to develop educational materials for a
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)
      program intervention in Denver, Colorado. Despite accumulating evidence of the
      importance of docosahexaenoic acid (DHA) during pregnancy, there has been no
      attempt to develop a targeted nutrition intervention to improve birth outcomes
      among high-risk women. The goal of the Omega-3 for Baby and Me intervention, for
      which these materials were developed, is to increase the consumption of DHA-rich
      foods to decrease the risk for premature delivery and low-birth weight babies
      among this population. METHOD: Following collection of data from eight focus
      groups among the target audience, the principles of the Health Belief Model were
      used to develop materials to address the needs, barriers, and motivators of this
      audience. In addition, process evaluation pilot testing was used to evaluate
      recipes and logos during the material development. RESULTS: Materials developed
      for this intervention include a logo, 9-month calendar, stickers, shopping lists,
      recipes, recipe holder, magnetic clip, nylon pouch, and recruitment materials.
      CONCLUSION: The use of focus groups and pilot testing increased the target
      audience acceptance of education materials that are being used for the Omega-3
      for Baby and Me intervention. Successful outcomes from the Omega-3 for Baby and
      Me intervention, i.e., decreasing the incidence of preterm birth and low-birth
      weight, will have implications for supplemental food policies at state and
      national levels.

PMID- 15965626
TI  - Perinatal periods of risk: analysis of fetal-infant mortality rates in Kansas
      City, Missouri.
AB  - OBJECTIVES: The Perinatal Periods of Risk (PPOR) technique was used to analyze
      resident fetal and infant death data from Kansas City, Missouri, for the period
      1998-2002. Results offer important information that can be used to develop
      community-based prevention strategies related to racial/ethnic disparities in
      infant mortality rates (IMR). METHODS: The PPOR approach for fetal and infant
      mortality can be mapped by birthweight at delivery and time of death into four
      strategic prevention areas: 1) Maternal Health/Prematurity (MHP), 2) Maternal
      Care (MC), 3) Newborn Care (NC), and 4) Infant Health (IH). For this analysis,
      all fetal and infant death certificates from the metropolitan Kansas City area
      were linked to their birth certificates and those associated with residents of
      Kansas City, Missouri, proper were used to create the dataset used in this
      analysis. Due to the small number of fetal and infant deaths among other ethnic
      groups, the analysis was restricted to a comparison of the disparity of IMR
      between Blacks, Whites, and a national non-Hispanic white reference group. The
      Kitagawa formula was used to determine contribution to excess deaths from
      birthweight-specific mortality and birthweight distribution rates. Logistic
      regression techniques were used to identify risk factors for death among Black
      fetuses and infants with very low birthweights and also deaths due to sudden
      infant death syndrome (SIDS). RESULTS: The PPOR analysis showed that of the
      excess deaths among black infants, when compared to a national reference group,
      47% was attributable to MHP and another 29% was attributable to IH. Differences
      in MC and NC only accounted for 27 and 8% of the total excess deaths. During the
      study period, rates of sudden infant death syndrome (SIDS) were found to be
      significantly higher among Blacks as compared to Whites (2.12 vs. 0.81 per
      1,000). An analysis of maternal characteristics for SIDS deaths among blacks
      using a step-wise logistic regression model, found that maternal age less than 20
      years old, previous births, inadequate prenatal care, and being a Medicaid
      recipient were significant-adjusted odds ratios of 23.7 (95% Cl 10.48, 53.67),
      8.4 (95% Cl 3.64, 19.21), 2.9 (95% Cl 1.38, 6.05) and 2.5 (95% Cl 1.04, 5.84),
      respectively. CONCLUSIONS: PPOR is an easy to use approach that helps focus
      community initiatives for improving maternal and infant health. In Kansas City,
      Missouri, efforts to further lower IMR in blacks can be achieved through the
      reduction of risk factors affecting maternal health and through maternal
      education to improve infant health.

PMID- 15965627
TI  - Financial burden for families of children with special health care needs.
AB  - OBJECTIVES: We describe family finance-related burden experienced by families
      with children with special health care needs (CSHCN). The paper further seeks to
      describe correlates of family financial burden. METHODS: We examined correlates
      of family finance-related burden using multivariate methods and the National
      Survey of CSHCN, a nationally representative cross-sectional survey of CSHCN. We
      also examined state-level correlations. RESULTS: Fully 40% of families with
      CSHCN, or 3,746,000 families nation-wide, experience financial burden related to
      their child's condition. Experiencing a finance-related problem is negatively
      associated with Maternal and Child Health Bureau (MCHB) indicators and positively
      associated with poor-child health status. States that better meet MCHB indicators
      generally have lower levels of family finance-related problems. CONCLUSIONS:
      Families with CSHCN have high levels of finance-related family problems.
      Development of appropriate systems of care appears to offer a mechanism for
      alleviating the financial burdens of these families.

PMID- 15965628
TI  - Legal decisions of preadolescent and adolescent defendants: predictors of
      confessions, pleas, communication with attorneys, and appeals.
AB  - While there is an increasing recognition that developmental differences may exist
      in legal decision-making, little research has examined this. This study examined
      the legal judgments of 152 defendants aged 11-17 (73 females, 79 males).
      Adolescents aged 15 and younger were more likely than older adolescents to
      confess and waive their right to counsel, and less likely to report that they
      would appeal their case or discuss disagreements with their attorneys. Also,
      while adolescents aged 15-17 were more likely to confess, plead guilty, and
      accept a plea bargain if they perceived that there was strong evidence against
      them, younger defendants' legal decisions were not predicted by the strength of
      evidence. Importantly, defendants with poor legal abilities were more likely to
      waive legal protections, such as the right to counsel and to appeal. Defendants
      from below-average socioeconomic backgrounds were more likely to waive their
      interrogation rights, and defendants from ethnic minority groups were less likely
      to report that they would disclose information to their attorneys. The advice of
      attorneys, parents, and peers emerged as important predictors of plea decisions.
      None of the defendants reported that their parents advised them to assert the
      right to silence during police interrogation.

PMID- 15965629
TI  - Suspect/foil identification in actual crimes and in the laboratory: a reality
      monitoring analysis.
AB  - Four reality monitoring variables were used to discriminate suspect from foil
      identifications in 183 actual criminal cases. Four hundred sixty-one
      identification attempts based on five and six-person lineups were analyzed. These
      identification attempts resulted in 238 suspect identifications and 68 foil
      identifications. Confidence, automatic processing, eliminative processing and
      feature use comprised the set of reality monitoring variables. Thirty-five verbal
      confidence phrases taken from police reports were assigned numerical values on a
      10-point confidence scale. Automatic processing identifications were those that
      occurred "immediately" or "without hesitation." Eliminative processing
      identifications occurred when witnesses compared or eliminated persons in the
      lineups. Confidence, automatic processing and eliminative processing were
      significant predictors, but feature use was not. Confidence was the most
      effective discriminator. In cases that involved substantial evidence extrinsic to
      the identification 43% of the suspect identifications were made with high
      confidence, whereas only 10% of the foil identifications were made with high
      confidence. The results of a laboratory study using the same predictors generally
      paralleled the archival results. Forensic implications are discussed.

PMID- 15965630
TI  - PC_Eyewitness and the sequential superiority effect: computer-based lineup
      administration.
AB  - Computer technology has become an increasingly important tool for conducting
      eyewitness identifications. In the area of lineup identifications, computerized
      administration offers several advantages for researchers and law enforcement.
      PC_Eyewitness is designed specifically to administer lineups. To assess this new
      lineup technology, two studies were conducted in order to replicate the results
      of previous studies comparing simultaneous and sequential lineups. One hundred
      twenty university students participated in each experiment. Experiment 1 used
      traditional paper-and-pencil lineup administration methods to compare
      simultaneous to sequential lineups. Experiment 2 used PC_Eyewitness to administer
      simultaneous and sequential lineups. The results of these studies were compared
      to the meta-analytic results reported by N. Steblay, J. Dysart, S. Fulero, and R.
      C. L. Lindsay (2001). No differences were found between paper-and-pencil and
      PC_Eyewitness lineup administration methods. The core findings of the N. Steblay
      et al. (2001) meta-analysis were replicated by both administration procedures.
      These results show that computerized lineup administration using PC_Eyewitness is
      an effective means for gathering eyewitness identification data.

PMID- 15965631
TI  - Psychopathy, conduct disorder, and stigma: does diagnostic labeling influence
      juvenile probation officer recommendations?
AB  - This study investigated the potential influence of labeling a juvenile as
      psychopathic. Juvenile probation officers (JPOs; N = 260) rendered hypothetical
      recommendations based on eight mock psychological evaluations. The evaluations
      varied the presence of two diagnostic criteria (antisocial behavioral history and
      psychopathic personality traits) and diagnostic labels (psychopathy, conduct
      disorder, no diagnosis) in order to distinguish criterion effects from labeling
      effects. The diagnostic criteria of antisocial behavior had a substantial effect
      on JPO recommendations (effect sizes .50-.79), while the diagnostic criteria of
      psychopathic personality traits had a more limited effect. Surprisingly,
      diagnostic labels had little effect, and there were no appreciable differences
      between conduct disorder and psychopathy diagnoses. These findings illustrate the
      importance of distinguishing diagnostic criterion effects from diagnostic
      labeling effects.

PMID- 15965632
TI  - Assessing violence risk in stalking cases: a regression tree approach.
AB  - Advances in the field of risk assessment have highlighted the importance of
      developing and validating models for problematic or unique subgroups of
      individuals. Stalking offenders represent one such subgroup, where fears of and
      potential for violence are well-known and have important implications for safety
      management. The present study applies a Classification and Regression Tree (CART)
      approach to a sample of stalking offenders in order to help further the process
      of identifying and understanding risk assessment strategies. Data from 204
      stalking offenders referred for psychiatric evaluation to a publicly-funded
      clinic were used to develop and assess putative risk factors. A series of nested
      models were used to generate tree algorithms predicting violence in this sample
      of offenders. Both simplified and more extensive models generated high levels of
      predictive accuracy that were roughly comparable to logistic regression models
      but much more straightforward to apply in clinical practice. Jack-knifed cross
      validation analyses demonstrated considerable shrinkage in the CART, although the
      models were still comparable to many other actuarial risk assessment instruments.
      Logistic regression models were much more resilient to cross-validation, with
      relatively modest loss in predictive power.

PMID- 15965633
TI  - Miranda comprehension in adults with mental retardation and the effects of
      feedback style on suggestibility.
AB  - Interrogations present several major challenges to persons with mental
      retardation (MR). Sixty adults with mild MR completed measures of Miranda
      comprehension and tendency to yield to leading questions. In addition,
      suggestibility was assessed based on whether participants revised answers to
      questions in response to unfriendly, friendly, or neutral feedback to original
      responses. Furthermore, we examined how expressed confidence in answers to
      repeated questions varied with the type of feedback received. Results revealed
      that participants demonstrated marked difficulties understanding their Miranda
      rights and greater likelihood of changing answers to questions for which they
      received friendly feedback than for questions for which they received unfriendly
      or neutral feedback. Most participants who received positive reinforcement for
      their answers on a second trial expressed confidence about improvement from trial
      1 to trial 2, although accuracy did not improve. Implications of these results
      are reviewed.

PMID- 15965634
TI  - [Glottic laryngeal carcinoma. Tis, T1 and T2--long term results after laser
      resection].
AB  - BACKGROUND: Endoscopic laser resection is one treatment modality for early
      glottic carcinoma. Benefits are the preservation of laryngeal structure without
      tracheotomy, the short duration of treatment, low traumatisation and good
      functional results. METHODS: From 1989 to 1999, 143 patients with an isolated and
      previously untreated glottic squamous cell carcinoma were treated by CO2
      endoscopic laser resection. The tumors were classified as carcinoma in situ (Tis)
      in seven cases, T1 tumor (T1N0M0) in 91 patients and T2 tumor (T2N0M0) in 45
      cases. Median follow-up was 5 years. RESULTS: For the group of Tis and T1
      carcinomas, 86 of 98 patients were free of recurrences. The 12 recurrences
      (12.2%) were treated by repeated laser surgery and laryngectomy (four patients).
      None of these patients died of tumor related causes. For patients with T2
      carcinomas, the overall recurrence rate was 28.9% (13 patients). In six patients,
      a total laryngectomy had to be performed and one patient died because of tumor
      recurrence. The relapse free survival estimate using the Kaplan-Meier method was
      87% for Tis and T1 carcinomas and 70% for T2 carcinomas. The overall laryngeal
      preservation rate was 95% for Tis and T1 carcinomas and 85% for T2 tumors. All
      recurrences occurred within 4 years of primary surgery. CONCLUSION: The results
      suggest that the oncological outcome after endoscopic laser surgery is comparable
      to conventional open partial resections.

PMID- 15965635
TI  - SPA therapy in fibromyalgia: a randomised controlled clinic study.
AB  - OBJECTIVE: The aim of the present study is to evaluate the effectiveness of spa
      therapy in the management of fibromyalgia. METHODS: Thirty women with
      fibromyalgia were randomly assigned to either a spa therapy group or a control
      group. The spa therapy group (n = 16) had spa treatment for 2 weeks in addition
      to their medical treatment. The control group (n = 14) continued to have their
      medical treatment and/or daily exercises. An investigator who was blinded for the
      intervention assessed all the patients for 9 months. Improvements in Fibromyalgia
      Impact Questionnaire (FIQ), pain and number of tender points were primary
      outcomes. Secondary outcome measures were improvement in sleep disturbance,
      fatigue, gastrointestinal symptoms, anxiety, Beck Depression Inventory and
      patient's global evaluation. RESULTS: the spa group was found to be superior to
      the control group at the end of intervention in terms of FIQ, pain, tender point
      count, fatigue and patients' global assessment. This superiority remained for 6
      months in FIQ, 1 month in pain and tender point count. CONCLUSION: It was
      concluded that the addition of spa therapy to medical therapy has both short- and
      long-term beneficial effects in female patients with fibromyalgia.

PMID- 15965636
TI  - Specific immunotherapy-induced Sjogren's syndrome.
AB  - BACKGROUND: Allergen-specific immunotherapy (SIT) is a well-documented treatment
      for allergic rhinitis, asthma, and allergy to bee venoms. Side-effects of SIT in
      long-term have not been well documented yet. Herein, we report a case of
      Sjogren's syndrome following SIT. CASE: The patient, a 25-year-old Caucasian
      woman, was started on subcutaneous grass-pollen immunotherapy. The patient's
      autoantibodies before the SIT screening tests were negative. We determined that
      anti-extractable nuclear antigen (ENA) was positive (ENA = 98.4, normal range 0
      25 U) on routine screening tests at 44 weeks of her treatment, and then SIT was
      discontinued. The patient complained of burning and itching in her eyes for 6
      months. Schirmer's and salivary flow tests were positive. Although antinuclear
      antigen and rheumatoid factor were negative, anti-SS-A/Ro was positive. Viral
      hepatitis markers were negative. Minor salivary-gland biopsy was performed, which
      showed grade 4 sialoadenitis. The HLA type of the patient was B55 (B22), Bw6, Cw1
      for class I and DR11, DR52, DQ7 (DQ3) for class II. After the immunotherapy had
      been stopped, there were no changes in the symptoms and laboratory findings of
      the patient during the 1st year of follow-up. CONCLUSION: This is the first case
      to be reported of Sjogren's syndrome following SIT. Patients undergoing SIT must
      be carefully followed up for the development of autoimmunity and an autoimmune
      disease.

PMID- 15965637
TI  - An unusual case of osteomalacia as the presenting feature of coeliac disease.

PMID- 15965638
TI  - Endothelial dysfunction in patients with primary Sjogren's syndrome.
AB  - The aim of this study was to determine the endothelial function in patients with
      primary Sjogren's syndrome (SS). We also aimed to determine whether endothelial
      (dys)function correlates with extraglandular manifestations, specific
      autoantibodies and the severity of salivary gland involvement of SS. Endothelium
      dependent vasodilation and endothelium-independent vasodilation of the brachial
      artery were assessed by a high-resolution ultrasound on 25 patients with primary
      SS and on 29 healthy controls. Patients with primary SS had significantly less
      mean endothelium-dependent vasodilation than did controls (3.0 +/- 0.4% vs 4.2 +/
      0.3%; p = 0.012). Endothelium-independent vasodilation induced by sublingual
      glycerol trinitrate was not different between the two groups (12.9 +/- 1.4% vs
      14.1 +/- 1.2%; p = 0.86). We concluded that endothelium-dependent vasodilation
      was impaired in primary SS patients, in particular those presenting with
      Raynaud's phenomenon, when compared with the healthy controls and this impairment
      was not associated with the presence of RF, ANA, anti-Ro/SS-A, anti-La/SS-B and
      with the other extraglandular manifestations of the disease.

PMID- 15965639
TI  - Muscular polyarteritis nodosa as a cause of fever of undetermined origin: a case
      report and review of the literature.
AB  - We describe an unusual presentation of a localized form of polyarteritis nodosa
      (PAN) manifested by fever of undetermined origin (FUO). Biopsies of the
      gastrocnemius muscle revealed necrotizing arteritis and initiation of
      prednisolone (PSL) brought rapid response. The PAN localized to muscle is rare;
      furthermore, this disease presented as FUO is very rare. We want to increase
      awareness that muscle can be also a single-affected site as well as other well
      known sites such as appendix, gallbladder, uterus or testis, and skin. Since
      there is no single appellation for this disease, we would like to propose the
      term "muscular PAN".

PMID- 15965640
TI  - Familial Mediterranean fever protracted febrile myalgia in children: report of
      two cases.

PMID- 15965641
TI  - [Incidental carcinoma of the prostate: can we and should we recommend radical
      prostatectomy?].
AB  - INTRODUCTION: There is controversy regarding tumor control of incidental prostate
      cancer (PC). We evaluated in a large cohort if we can recommend radical
      prostatectomy after TURP. MATERIAL AND METHOD: In 52 (4.3%) from a total of 1207
      patients undergoing radical prostatectomy the diagnosis had been made by TURP. In
      a retrospective analysis we evaluated morbidity, histopathological results, and
      tumor control of pT1a/b tumors. RESULTS: The number of incidentally detected PC
      decreased with time. In 5.8% in the TURP group and in 0.5% of the needle biopsy
      group, there was no residual tumor found (p<0.001). Morbidity was similar +/-
      TURP with the exception of operation time (206 vs 188 min) and catheter duration
      (19.3 vs 17.3 days). Postoperative continence was identical. There was no
      difference in tumor control for local recurrence-free survival and PSA-free
      survival with and without TURP. CONCLUSIONS: The rate of incidentally detected PC
      by TURP decreases over time, but in almost all cases we found clinically relevant
      cancer. TURP is not an adverse prognostic factor and morbidity is similar
      compared with patients who were diagnosed by needle biopsy. Our data confirm that
      we should recommend radical prostatectomy to patients who are candidates for
      further curative therapy.

PMID- 15965642
TI  - [Use of free dermal grafts in urology].
AB  - Plastic reconstructive surgery is of increasing importance in urology. The choice
      of the optimal material, for example dermal graft or musculocutaneous graft, is
      decisive for the operative success of each procedure. We present the technique,
      indications, innovations, and mutual fields with other operative disciplines.

PMID- 15965643
TI  - Functional characterization of Schizosaccharomyces pombe neutral trehalase
      altered in phosphorylatable serine residues.
AB  - The activation of neutral trehalase (Ntp1) by metabolic and physical stresses in
      Schizosaccharomyces pombe is dependent on protein kinases Pka1 or Sck1. Mutant
      ntp1 alleles altered for potentially phosphorylatable serine residues within the
      regulatory domain of the enzyme were integrated under the control of the native
      promoter in an ntp1-deleted background. The trehalase variants were expressed to
      a level similar to that of wild type trehalase from control cells. Wild type
      trehalase protein accumulated and became activated upon stress while a single
      change in the evolutionary conserved perfect consensus site for Pka1-dependent
      phosphorylation (Ser71), as well as point mutations in two other putative
      phosphorylation sites (Ser6, Ser51), produced inactive trehalases unresponsive to
      stress. Trehalose content in the trehalase mutated strains increased upon salt
      stress to a level comparable to that shown by an ntp1-deleted mutant. When
      exposed to heat shock, trehalose hyperaccumulated in the ntp1-null strain lacking
      trehalase protein and this phenotype was shown by some (Ser71), but not all,
      strains with serine mutated trehalases. The mutant trehalases retained the
      ability to form complexes with trehalose-6-phosphate synthase. These data support
      a role of potentially phosphorylated specific sites for the activation of S.
      pombe neutral trehalase and for the heat shock-induced accumulation of trehalose.

PMID- 15965644
TI  - The Q283P amino-acid change in HFE leads to structural and functional
      consequences similar to those described for the mutated 282Y HFE protein.
AB  - In Caucasians, 4-35% of hemochromatosis patients carry at least one chromosome
      without a common HFE mutation (i.e. C282Y, H63D and S65C). Several studies have
      now shown that iron overload phenotypes in such patients can be associated with
      uncommon HFE mutations. We previously supported implication of the C282Y/Q283P
      compound heterozygous genotype in hemochromatosis phenotypes and, based on
      molecular dynamics simulations, proposed that the Q283P substitution prevents
      normal folding of the HFE alpha3-domain. In the current work, we have used HeLa
      cells carrying wild-type or Q283P-mutant HFE cDNA under the control of a
      tetracycline-sensitive promoter to functionally characterise the Q283P mutation.
      Experiments using cells over-expressing wild-type HFE confirm the existence of
      beta2microglobulin(beta2m)/HFE and HFE/transferrin receptor 1 (TfR1)
      interactions, as well as the capacity of HFE to reduce transferrin-mediated iron
      uptake. In contrast, neither beta2m/HFE nor HFE/TfR1 complex formation was
      detected in cells over-expressing the mutated form of HFE. Moreover, the 283P HFE
      protein was found to have a very limited effect on the major cellular iron uptake
      pathway. Combined, our results indicate that the Q283P mutation leads to
      structural and functional consequences similar to those described for the main
      hereditary hemochromatosis mutation. As a consequence, our study has implications
      for the screening of hemochromatosis patients that have one or two copies of HFE
      which lack the main mutations. It also highlights that protein structure
      prediction methods could be more generally used to better interpret relationships
      between rare genotypes and molecular diagnosis of a human inherited disorder.

PMID- 15965645
TI  - Dendritic cells pulsed with gp96-peptide complexes derived from human
      hepatocellular carcinoma (HCC) induce specific cytotoxic T lymphocytes.
AB  - Dendritic cells (DCs) are one of the most potent antigen-presenting cells (APCs)
      capable of activating immune responses. Different forms of tumor antigens have
      been used to load DCs to initiate tumor-specific immune responses. Heat shock
      proteins (HSPs) are considered natural adjuvants which have the ability to
      chaperone peptides associated with them presented efficiently by interaction with
      professional APCs through specific receptors. In the present study, we used HSP,
      gp96-peptide complexes, derived from human hepatocellular carcinoma (HCC) cells
      as antigens for pulsing DCs. We found that gp96-peptide complexes derived from
      HCC cells induced the maturation of DCs by enhancing expression of human
      leukocyte antigen class II, CD80, CD86, CD40, and CD83. The matured DCs
      stimulated a high level of autologous T cell proliferation and induced HCC
      specific cytotoxic T lymphocytes, which specifically killed HCC cells by a major
      histocompatability complex (MHC) class I restricted mechanism. These findings
      demonstrate that DCs pulsed with gp96-peptide complexes derived from HCC cells
      are effective in activating specific T cell responses against HCC cells.

PMID- 15965646
TI  - Importance of signaling via the IFN-alpha/beta receptor on host cells for the
      realization of the therapeutic benefits of cyclophosphamide for mice bearing a
      large MOPC-315 tumor.
AB  - Here we show that low-dose cyclophosphamide (CY), that depends for its
      therapeutic effectiveness on the immunopotentiating activity of the drug for T
      cell-mediated tumor-eradicating immunity, is curative for approximately 80% of
      wild-type (WT) mice bearing a large s.c. MOPC-315 tumor, but only for
      approximately 10% of IFN-alpha/betaR-/- mice bearing a large s.c. MOPC-315 tumor.
      Histopathological examination of the s.c. tumors of such mice on day 4 after the
      chemotherapy revealed that the low dose of CY led to accumulation of T
      lymphocytes in both the WT and the IFN-alpha/betaR-/- mice. However, in the CY
      treated tumor bearing WT mice the T lymphocytes were present throughout the tumor
      mass and in direct contact with tumor cells, but in the CY treated tumor bearing
      IFN-alpha/betaR-/- mice most of the T lymphocytes remained in blood vessels. In
      addition to being important for CY-induced transendothelial migration of T
      lymphocytes into the tumor mass, we show here that signaling via the IFN
      alpha/betaR is also important for CY-induced control of metastatic tumor
      progression in the spleen and liver of the tumor bearing mice. Finally, CY cured
      tumor bearing WT mice were resistant to a subsequent challenge with MOPC-315
      tumor cells, but the few CY cured tumor bearing IFN-alpha/betaR-/- mice were not.
      Thus, signaling via the IFN-alpha/betaR on host cells in MOPC-315 tumor bearers
      is important for CY-induced: (a) transendothelial migration of T lymphocytes into
      the tumor mass and the eradication of the primary tumor, (b) control of
      metastatic tumor progression, and (c) resistance to a subsequent tumor challenge.

PMID- 15965647
TI  - Development of an allogeneic whole-cell tumor vaccine expressing xenogeneic gp100
      and its implementation in a phase II clinical trial in canine patients with
      malignant melanoma.
AB  - A xenogeneic melanoma-antigen-enhanced allogeneic tumor cell vaccine (ATCV) is an
      appealing strategy for anti-cancer immunotherapy due to its relative ease of
      production, and the theoretical possibility that presentation of a multiplex of
      antigens along with a xenogeneic antigen would result in cross-reaction between
      the xenogeneic homologs and self-molecules, breaking tolerance and ultimately
      resulting in a clinically relevant immune response. In this study, we evaluated
      the efficacy of such a strategy using a xenogeneic melanoma differentiation
      antigen, human glycoprotein 100 (hgp100) in the context of a phase II clinical
      trial utilizing spontaneously arising melanoma in pet dogs. Our results
      demonstrate that the approach was well tolerated and resulted in an overall
      response rate (complete and partial response) of 17% and a tumor control rate
      (complete and partial response and stable disease of >6 weeks duration) of 35%.
      Dogs that had evidence of tumor control had significantly longer survival times
      than dogs that did not experience control. Delayed type hypersensitivity (DTH) to
      17CM98 canine melanoma cells used in the whole cell vaccine was enhanced by ATCV
      and correlated with clinical response. In vitro cytotoxicity was enhanced by
      ATCV, but did not correlate with clinical response. Additionally, anti-hgp100
      antibodies were elicited in response to ATCV in the majority of patients tested;
      however, this also did not correlate with clinical response. This approach, along
      with further elucidation of the mechanisms of tumor protection after xenogeneic
      immunization, may allow the development of more rational vaccines. This trial
      also further demonstrates the utility of spontaneous tumors in companion animals
      as a valid translational model for the evaluation of novel vaccine therapies.

PMID- 15965648
TI  - A new recombined double low restorer line for the Ogu-INRA cms in rapeseed
      (Brassica napus L.).
AB  - A major objective of breeders using the Ogu-INRA cytoplasmic male sterility (cms)
      system in rapeseed (Brassica napus L.) is to obtain double low restorer lines
      with a shorter introgression and a good agronomic value. The development of low
      glucosinolate content (low GC) restorer lines often occurs through the deletion
      of a part of the introgression. One of these lines has lost the radish Pgi-2
      allele expression, without recovering that of the rapeseed Pgi-2 allele. This
      line shows a defect in the meiotic transmission of the restorer gene Rfo and a
      very poor agronomic value. We initiated a programme to force non-spontaneous
      recombination between this Rfo-carrying introgression and the rapeseed homologous
      chromosome from a low GC B. napus line. Gamma ray irradiation was used to induce
      chromosome breakage just prior meiosis aiming at just such a recombination. Low
      GC cms plants were crossed with the pollen of irradiated plants that were
      heterozygous for this introgression. The F(2) families were scored for their
      vigour, transmission rate of Rfo and female fertility. One family of plants,
      R2000, showed an improved behaviour for these three traits. This family presented
      a unique combination of molecular markers when compared to other rapeseed
      restorers analysed, which suggests that the recombination event allowed the
      recovery of B. oleracea genetic information that was originally replaced by the
      radish introgression in the original restorers. This resulted in a duplicated
      region (originating from radish and B. oleracea) on the chromosome carrying the
      introgression in the R2000 family.

PMID- 15965649
TI  - Powdery mildew resistance and Lr34/Yr18 genes for durable resistance to leaf and
      stripe rust cosegregate at a locus on the short arm of chromosome 7D of wheat.
AB  - The incorporation of effective and durable disease resistance is an important
      breeding objective for wheat improvement. The leaf rust resistance gene Lr34 and
      stripe rust resistance gene Yr18 are effective at the adult plant stage and have
      provided moderate levels of durable resistance to leaf rust caused by Puccinia
      triticina Eriks. and to stripe rust caused by Puccinia striiformis Westend. f.
      sp. tritici. These genes have not been separated by recombination and map to
      chromosome 7DS in wheat. In a population of 110 F(7) lines derived from a
      Thatcher x Thatcher isogenic line with Lr34/Yr18, field resistance to leaf rust
      conferred by Lr34 and to stripe rust resistance conferred by Yr18 cosegregated
      with adult plant resistance to powdery mildew caused by Blumeria graminis (DC) EO
      Speer f. sp. tritici. Lr34 and Yr18 were previously shown to be associated with
      enhanced stem rust resistance and tolerance to barley yellow dwarf virus
      infection. This chromosomal region in wheat has now been linked with resistance
      to five different pathogens. The Lr34/Yr18 phenotypes and associated powdery
      mildew resistance were mapped to a single locus flanked by microsatellite loci
      Xgwm1220 and Xgwm295 on chromosome 7DS.

PMID- 15965650
TI  - Toward closing rice telomere gaps: mapping and sequence characterization of rice
      subtelomere regions.
AB  - Despite the collective efforts of the international community to sequence the
      complete rice genome, telomeric regions of most chromosome arms remain
      uncharacterized. In this report we present sequence data from subtelomere regions
      obtained by analyzing telomeric clones from two 8.8 x genome equivalent 10-kb
      libraries derived from partial restriction digestion with HaeIII or Sau3AI
      (OSJNPb HaeIII and OSJNPc Sau3AI). Seven telomere clones were identified and
      contain 25-100 copies of the telomere repeat (CCCTAAA)(n) on one end and unique
      sequences on the opposite end. Polymorphic sequence-tagged site markers from five
      clones and one additional PCR product were genetically mapped on the ends of
      chromosome arms 2S, 5L, 10S, 10L, 7L, and 7S. We found distinct chromosome
      specific telomere-associated tandem repeats (TATR) on chromosome 7 (TATR7) and on
      the short arm of chromosome 10 (TATR10s) that showed no significant homology to
      any International Rice Genome Sequencing Project (IRGSP) genomic sequence. The
      TATR7, a degenerate tandem repeat which is interrupted by transposable elements,
      appeared on both ends of chromosome 7. The TATR10s was found to contain an
      inverted array of three tandem repeats displaying an interesting secondary
      folding pattern that resembles a telomere loop (t-loop) and which may be involved
      in a protective function against chromosomal end degradation.

PMID- 15965651
TI  - Genetic characterisation of dough rheological properties in a wheat doubled
      haploid population: additive genetic effects and epistatic interactions.
AB  - Doubled haploid lines (n = 160) from a cross between wheat cultivars 'Cranbrook'
      (high dough extensibility) and 'Halberd' (low dough extensibility) were grown at
      three Australian locations. The parents differ at all high- and low-molecular
      weight glutenin loci. Dough rheological parameters were measured using small
      scale testing procedures, and quantitative trait locus (QTL) mapping procedures
      were carried out using an existing well-saturated genetic linkage map for this
      cross. Genetic parameters were estimated using three software packages:
      QTLCartographer, Epistat and Genstat. Results indicated that environmental
      factors are a major determinant of dough extensibility across the three trial
      sites, whereas genotypic factors are the major determinants of dough strength.
      Composite interval mapping analysis across the 21 linkage groups revealed that as
      expected, the main additive QTLs for dough rheological properties are located at
      the high- and low-molecular-weight glutenin loci. A new QTL on chromosome 5A for
      M-extensibility (a mixograph-estimated measure of extensibility) was detected.
      Analysis of epistatic interactions revealed that there were significant
      conditional epistatic interactions related with the additive effects of glutenin
      loci on dough rheological properties. Therefore, the additive genetic effects of
      glutenins on dough rheological properties are conditional upon the genetic
      background of the wheat line. The molecular basis of the interactions with the
      glutenin loci may be via proteins that modify or alter the gluten protein matrix
      or variations in the expression level of the glutenin genes. Reverse-phase high
      performance liquid chromatography analysis of the molar number of individual
      glutenin subunits across the population showed that certain conditional epistases
      resulted in increased expression of the affected glutenin. The epistatic
      interactions detected in this study provide a possible explanation of the
      variable genetic effects of some glutenins on quality attributes in different
      genetic backgrounds and provide essential information for the accurate prediction
      of glutenin related variance in marker-assisted wheat breeding.

PMID- 15965652
TI  - The pattern of genetic diversity of Guinea-race Sorghum bicolor (L.) Moench
      landraces as revealed with SSR markers.
AB  - The Guinea-race of sorghum [Sorghum bicolor (L.) Moench] is a predominantly
      inbreeding, diploid cereal crop. It originated from West Africa and appears to
      have spread throughout Africa and South Asia, where it is now the dominant
      sorghum race, via ancient trade routes. To elucidate the genetic diversity and
      differentiation among Guinea-race sorghum landraces, we selected 100 accessions
      from the ICRISAT sorghum Guinea-race Core Collection and genotyped these using 21
      simple sequence repeat (SSR) markers. The 21 SSR markers revealed a total of 123
      alleles with an average Dice similarity coefficient of 0.37 across 4,950 pairs of
      accessions, with nearly 50% of the alleles being rare among the accessions
      analysed. Stratification of the accessions into 11 countries and five eco
      regional groups confirmed earlier reports on the spread of Guinea-race sorghum
      across Africa and South Asia: most of the variation was found among the
      accessions from semi-arid and Sahelian Africa and the least among accessions from
      South Asia. In addition, accessions from South Asia most closely resembled those
      from southern and eastern Africa, supporting earlier suggestions that sorghum
      germplasm might have reached South Asia via ancient trade routes along the
      Arabian Sea coasts of eastern Africa, Arabia and South Asia. Stratification of
      the accessions according to their Snowden classification indicated clear genetic
      variation between margeritiferum, conspicuum and Roxburghii accessions, whereas
      the gambicum and guineense accessions were genetically similar. The implications
      of these findings for sorghum Guinea-race plant breeding activities are
      discussed.

PMID- 15965654
TI  - Expression of neuronal nitric oxide synthase (nNOS) and nitric-oxide-induced
      changes in cGMP in the urothelial layer of the guinea pig bladder.
AB  - The urothelium plays a sensory role responding to deformation of the bladder
      wall; this involves the release of adenosine trisphosphate (ATP) and nitric oxide
      (NO), which affect afferent nerve discharge and bladder sensation. The urothelial
      cells responsible for producing ATP and NO and the cellular targets, other than
      afferent nerves, for ATP and NO remain largely unexplored. Sub-urothelial
      interstitial cells (SU-ICs) lie immediately below the urothelium and respond to
      NO with a rise in cGMP. To determine which cells might target SU-ICs by producing
      NO, areas of dome, lateral wall and base wall were treated with isobutyl-methyl
      xanthine, exposed to the NO donor diethylamino NONOate and then fixed for
      immunohistochemistry. Surface urothelial cells (SUCs) in the base and dome
      expressed neuronal nitric oxide synthase (nNOS), whereas those in the lateral
      wall did not. Distinct populations of SUCs were present in the bladder base. SUCs
      with significant amounts of nNOS lay adjacent to cells with low levels of nNOS.
      In specific base regions, the few SUCs present contained nNOS within discrete
      intracellular particles. In the basal urothelial cell (BUC) layer of the lateral
      wall, nNOS-positive (NOS(+)) BUCs neither showed an elevation in cGMP in response
      to NO, nor expressed the beta1 sub-unit of soluble guanylate cyclase, protein
      kinase I or protein kinase II. Thus, they produced but did not respond to NO. The
      BUC layer also stained for the stem cell factor c-Kit suggesting its involvement
      in urothelial cell development. No NOS(+) BUCs were present in the SUC-sparse
      region in the bladder base. Exogenous NO produced an elevation in cGMP in SUCs
      and SU-ICs. The distribution and proportion of these target cells varied between
      the dome, lateral wall and base. cGMP(+) SU-ICs were present as a dense layer in
      the bladder base but were rarely seen in the lateral wall, which contained
      nNOS(+) BUCs. No nNOS(+) BUCs and cGMP(+) SU-ICs were apparent in the dome. The
      degree of complexity in nNOS distribution and NO target cells is therefore
      greater than has previously been described and may reflect distinct physiological
      functions that have yet to be identified.

PMID- 15965653
TI  - Impaired expression of hepatic multidrug resistance protein 2 is associated with
      posthepatectomy hyperbilirubinemia in patients with biliary cancer.
AB  - BACKGROUND AND AIMS: Hyperbilirubinemia is a critical complication following
      hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a
      bilirubin transporter, is shown to be down-regulated by acute biliary obstruction
      in rats. However, little is known about the effect of chronic obstruction by
      malignancy on the MRP2 expression in patients or the association of MRP2
      expression with posthepatectomy hyperbilirubinemia. MATERIALS AND METHODS: The
      MRP2 expression before hepatectomy was determined by immunostaining and Western
      blotting in patients with biliary cancer. To directly determine the effect of
      chronic bile duct obstruction on the MRP2 expression, the expression levels were
      compared between the cholestatic and noncholestatic lobes in each of seven
      patients. In another 39 patients, the correlation of the MRP2 expression of the
      anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia,
      defined as a serum total bilirubin concentration>or=200 micromol/l, was
      evaluated. RESULTS: The MRP2 staining in the cholestatic lobes was weak and not
      restricted to the canalicular membrane, unlike the noncholestatic lobes. The
      expression levels in the cholestatic lobes were 45% of those in the
      noncholestatic lobes. Postoperative maximum bilirubin levels were significantly
      correlated with MRP2 expression of the anticipated remnant liver. The MRP2
      expression had been already impaired before hepatectomy in all patients who
      eventually developed severe hyperbilirubinemia. CONCLUSIONS: Decreased MRP2
      expression, caused by biliary obstruction due to cancer, is a possible risk
      factor for posthepatectomy severe hyperbilirubinemia.

PMID- 15965655
TI  - Cryptorchidism: an indicator of testicular dysgenesis?
AB  - Cryptorchidism is a common ailment of new-born boys, affecting 1-9% of full term
      boys at birth. Cryptorchidism has been associated with an increased risk of
      testicular cancer and reduced fertility. Aetiology of cryptorchidism remains
      obscure in most cases. Familial occurrence suggests a heritable susceptibility to
      cryptorchidism; however, seasonal variation in the incidence of cryptorchidism
      suggests that environmental factors also contribute. Testicular descent is
      characterised by androgen-dependent regression of cranial suspensory ligament and
      androgen + insulin-like hormone 3 (Ins l3)-dependent gubernacular outgrowth. Even
      though hormonal defects are rarely detected in patients, both hypo-and
      hypergonadotropic hormonal patterns have been associated with cryptorchidism.
      Moreover, cryptorchid boys have significantly reduced serum androgen bioactivity
      at 3 months of age when normal boys have a strong surge of reproductive hormones.
      Defects in Ins l3 action cause cryptorchidism in male mice, and over-expression
      in female mice causes ovarian descent. Defects in leucine-rich repeat-containing
      G-protein-coupled receptor 8/G-protein-coupled receptor affecting testis descent
      (LGR8/GREAT), the receptor for Ins l3, manifest the same phenotype as Ins l3
      knockout mutants. Even though mutations found in Ins l3 and LGR8/GREAT genes are
      not a common cause of cryptorchidism in patients, it remains to be resolved
      whether low Ins l3 levels during development are associated with cryptorchidism.
      Cryptorchidism may reflect foetal testicular dysgenesis that may later manifest
      as subfertility or testicular cancer.

PMID- 15965656
TI  - Abnormalities of testicular descent.
AB  - Testicular descent occurs in two stages. The transabdominal phase (8-15 weeks) is
      controlled by enlargement of the caudal genito-inguinal ligament (gubernaculum)
      and regression of the cranial ligament. Insulin-like 3 from the Leydig cell
      appears to be the prime stimulator of gubernacular growth, augmented by Mullerian
      inhibiting substance/anti-Mullerian hormone. Testosterone causes regression of
      the cranial ligament. The inguinoscrotal phase (25-35 weeks) requires the
      migration of the gubernaculum from the groin to the scrotum; this migration is
      guided by the genito-femoral nerve releasing calcitonin gene-related peptide
      under the influence of androgen. The neonatal gonocyte transforms into a type A
      spermatogonium at 3-12 months of age, a step that is now known to be crucial for
      subsequent fertility, as the stem cells for spermatogenesis are created in this
      structure. This step is blocked in undescended testis and, hence, orchidopexy is
      currently recommended at 6-12 months of age. Congenital cryptorchidism is caused
      by the failure of gubernacular migration to the scrotum (1%-2%) but we now
      recognise that another 1%-2% of boys have acquired cryptorchidism, secondary to
      the failure of spermatic cord elongation with growth of the boy. These latter
      cases come to operation at 5-10 years of age. Surgery remains the mainstay of
      treatment, as hormonal therapy has not been proven to be effective, presumably
      because testicular descent is a complex anatomical mechanism.

PMID- 15965657
TI  - Early prostate development and its association with late-life prostate disease.
AB  - The development of the prostate is an emerging priority area for prostate
      biologists. Early changes in prostate development permanently alter prostate
      morphology and function and an understanding of the permanent nature of early
      events that may influence the onset of late-life disease is vital. Two of the
      inherent problems involve associating exposure in early life with outcome in late
      life or maturity and accounting for the influence of genetic, environmental,
      dietary or metabolic factors during the intervening period. Any one of these
      factors, alone or in combination, might lead to an explanation of the
      discrepancies found in the literature regarding the influence of early changes to
      the prostate in later life. Therefore, it is important to establish a causal link
      between the hormonal changes that occur during the fetal/neonatal period and that
      imprint the gland and the onset of late-life pathology. In order to achieve this
      goal, several technical challenges need to be overcome to permit the objective
      assessment of prostate branching morphogenesis. Stereological techniques now
      allow the quantification of several parameters of branching morphogenesis and the
      identification of specific early changes that are permanent and irreversible with
      a late-life outcome. This methodology provides the means to determine the action
      of a range of genes or hormone/growth factors that have been implicated in
      prostate development and disease.

PMID- 15965658
TI  - Phenotypic and functional characterisation of follicle-associated epithelium of
      rectal lymphoid tissue.
AB  - Lymphoid follicles cluster in the terminal rectum of various animal species and
      of man and hence this site may be important in the development of immune
      responses to pathogens. For the induction of immune responses at mucosal sites,
      interplay is required between various cell types performing functions ranging
      from antigen-sampling cells via antigen-presenting cells to antigen-specific
      lymphocytes. Therefore, we have characterised the cell populations and relevant
      functioning of follicle-associated epithelium (FAE) and associated follicles in
      the terminal portion of rectum in cattle as a representative mammal.
      Immunohistochemical studies of this region identified immune cell subsets (CD4+,
      CD8+, WC 1+gammadelta, CD2+, CD 21+ and CD 40+ cells) characteristic of an immune
      inductive site. Examination of FAE identified a subset of cells with structural
      and functional features of antigen-sampling M-cells. Cells of the FAE and
      adjacent follicle-associated crypts expressed vimentin and a subset of these
      cells internalised microparticles, a further attribute of M-cells. The FAE cells
      were phenotypically heterogeneous and therefore the function and phenotype of
      these cell subsets requires further characterisation, particularly with respect
      to their potentially important role in the interaction of hosts with pathogens
      and the development of immune responses.

PMID- 15965659
TI  - The -174 IL-6 GG genotype is associated with a reduced risk of type 2 diabetes
      mellitus in a family sample from the National Heart, Lung and Blood Institute's
      Framingham Heart Study.
AB  - AIMS/HYPOTHESIS: We evaluated the -174 IL-6 gene polymorphism as a risk factor
      for type 2 diabetes mellitus in a family-based analysis. METHODS: We tested for
      associations between the -174 IL-6 G/C promoter polymorphism and fasting plasma
      glucose (FPG) and type 2 diabetes in a sample of 1,428 individuals from the
      largest 182 families in the National Heart, Lung and Blood Institute's Framingham
      Heart Study population. RESULTS: A significant association was found with FPG
      (p=0.01) and log (FPG) (p=0.005) using a modified family-based transmission
      disequilibrium test, the family-based association test (FBAT). The association
      between IL-6 genotype and FPG (p=0.035) and log (FPG) (p=0.03) was also found in
      the subset of families that were informative in FBAT using a mixed-effects
      regression model and strengthened after adjustment for potential confounders
      (p=0.008 for log [FPG]). The mean glucose level estimated from models with log
      (FPG) as the dependent variable for the GG genotype in the informative families
      was significantly lower (5.20+/-0.06 mmol/l) than for the GC (5.41+/-0.06 mmol/l)
      and CC (5.38+/-0.06 mmol/l) genotypes (p=0.03 for contrast between GG and GC
      genotypes). In the subset of informative families, the risk of type 2 diabetes
      associated with the GG genotype was lower relative to the GC and CC genotypes
      combined (potential confounder-adjusted, mixed-effects odds ratio 0.35, 95% CI
      0.14-0.88, p=0.026, unaffected n=391, affected n=32). CONCLUSIONS/INTERPRETATION:
      These results are consistent with a protective role for the -174 IL-6 G allele
      against type 2 diabetes and warrant further analysis of this polymorphism.

PMID- 15965660
TI  - Evaluation of a semiautomatic software tool for left ventricular function
      analysis with 16-slice computed tomography.
AB  - The purpose of the study was to evaluate a semiautomatic analysis tool for
      assessing global left ventricular myocardial function with multislice computed
      tomography (MSCT). We examined 33 patients with MSCT using 16x0.5 mm detector
      collimation and magnetic resonance imaging (MRI) on a 1.5-T scanner. MSCT data
      were analyzed using semiautomatic volumetric analysis software (ANET, CSCF-001A,
      Toshiba). This software tool automatically creates endo- and epicardial contours
      that can be manually corrected on all short-axis slices at all reconstructed time
      points within the cardiac cycle, based on a contour-detection and density
      threshold algorithm. All global left ventricular function parameters assessed
      with the semiautomatic MSCT software were highly correlated with the results of
      MRI. Bland-Altman analysis showed minor systematic overestimation of end
      diastolic (10.7 ml) and end-systolic volumes (5.6 ml) and underestimation of
      ejection fraction (2.1%) with MSCT as compared with MRI. The post-processing time
      was moderately but significantly longer with the MSCT software (15.9+/-2.8 min)
      than necessary for MRI (14.0+/-2.5 min, P<0.01), mainly as a result of the longer
      time required for uploading of the MSCT datasets, which were on average 54 times
      larger (1.3 GByte). In conclusion, it appears feasible to accurately assess
      global left ventricular function with MSCT in a reasonable post-processing time
      using a semiautomatic software tool.

PMID- 15965661
TI  - Importance of extracolonic findings at IV contrast medium-enhanced CT
      colonography versus those at non-enhanced CT colonography.
AB  - To compare the clinical importance of extracolonic findings at intravenous (IV)
      contrast-enhanced CT colonography versus those at non-enhanced CT colonography.
      IV contrast medium-enhanced (n=72) and non-enhanced (n=30) multidetector CT
      colonography was performed in 102 symptomatic patients followed by conventional
      colonoscopy on the same day. The impact of extracolonic findings on further work
      up and treatment was assessed by a review of patient records. Extracolonic
      findings were divided into two groups: either leading to further work up
      respectively having an impact on therapy or not. A total of 303 extracolonic
      findings were detected. Of those, 71% (215/303) were found on IV contrast
      enhanced CT, and 29% (88/303) were found on non-enhanced CT colonography. The
      extracolonic findings in 25% (26/102) of all patients led to further work up or
      had an impact on therapy. Twenty-two of these patients underwent CT colonography
      with IV contrast enhancement, and four without. The percentage of extracolonic
      findings leading to further work up or having an impact on therapy was higher for
      IV contrast-enhanced (31%; 22/72) than for non-enhanced (13%; 4/30) CT scans
      (P=0.12). IV contrast-enhanced CT colonography produced more extracolonic
      findings than non-enhanced CT colonography. A substantially greater proportion of
      findings on IV contrast-enhanced CT colonography led to further work up and
      treatment than did non-enhanced CT colonography.

PMID- 15965662
TI  - Magnetization transfer ratio in the brain of preterm subjects: age-related
      changes during the first 2 years of life.
AB  - To study the progress of myelination in preterm-born subjects by measuring the MT
      ratio (MTR) from birth, up to 24 months of corrected age. One hundred twenty-five
      preterm subjects (64 males and 61 females of gestational age 33+/-2.4 weeks with
      chronologic and corrected age of 9.3+/-5.1 and 7.7+/-5.1 months, respectively)
      with normal brain MR using classic sequences were further evaluated for MTR by
      using a three-dimensional gradient-echo sequence (TR=32/TE=8/flip angle=6 degrees
      4 mm/2 mm overlapping sections) with and without magnetization transfer prepulse.
      The magnetization transfer ratio was calculated as: MTR=(SIo-SIm)/SIox100%, where
      SIm refers to signal intensity from an image acquired with a MT prepulse and SIo
      the signal intensity from the image acquired without a MT prepulse. MTR increased
      asymptotically in the genu (R2=0.85) and splenium (R2=0.85) of the corpus
      callosum, the white matter of the frontal lobe (R2=0.91) and occipital lobe
      (R2=0.82), thalamus (R2=0.86), caudate nucleus (R2=0.67) and putamen (R2=0.71),
      reaching the 95% of the final value at the corrected age 18.7, 17.7, 15.6, 12.9,
      10.4, 9.2 and 6.4 months, respectively. This study shows age-related changes of
      the brain MTR and provides data that may be useful to assess disturbances in the
      progress of myelination.

PMID- 15965663
TI  - Probing the cell wall heterogeneity of micro-dissected wheat caryopsis using both
      active and inactive forms of a GH11 xylanase.
AB  - The external envelope of wheat grain (Triticum aestivum L. cv. Isengrain) is a
      natural composite whose tissular and cellular heterogeneity constitute a
      significant barrier for enzymatic cell wall disassembly. To better understand the
      way in which the cell wall network and tissular organization hamper enzyme
      penetration, we have devised a strategy based on in situ visualization of an
      active and an inactive form of a xylanase in whole-wheat bran and in three micro
      dissected layers (the outer bran, the inner bran and the aleurone layer). The
      main aims of this study were to (1) evaluate the role of cuticular layers as
      obstacles to enzyme diffusion, (2) assess the impact of the cell wall network on
      xylanase penetration, (3) highlight wall heterogeneity. To conduct this study, we
      created by in vitro mutagenesis a hydrolytically inactive xylanase that displayed
      full substrate binding ability, as demonstrated by the calculation of
      dissociation constants (K(d)) using fluorescence titration. To examine enzyme
      penetration and action, immunocytochemical localization of the xylanases and of
      feebly substituted arabinoxylans (AXs) was performed following incubation of the
      bran layers, or whole bran with active and inactive isoforms of the enzyme for
      different time periods. The data obtained showed that the micro-dissected layers
      provided an increased accessible surface for the xylanase and that the enzyme
      targeted cell walls were penetrated more quickly than those in intact bran.
      Examination of immunolabelling of xylanase indicated that the cuticle layers
      constitute a barrier for enzyme penetration in bran. Moreover, our data indicated
      that the cell wall network by itself physically restricts enzyme penetration.
      Inactive xylanase penetration was much lower than that of the active form, whose
      penetration was facilitated by the concomitant depletion of AXs in enzyme
      sensitive cell walls.

PMID- 15965664
TI  - [Acute abdomen].
AB  - Acute abdomen is not a disease entity on its own but describes a critical state
      of the patient which can be caused by numerous diseases. The surgeon and
      internist have to apply an interdisciplinary approach to enable a rapid decision
      on whether immediate laparotomy is mandatory. Few appropriate diagnostic
      procedures support decision making. In many cases there is an indication for
      immediate surgery, such as perforated gastric or duodenal ulcer, acute
      appendicitis, diverticulitis, ruptured aortic aneurysm, mechanic ileus,
      infarction of the mesenteric artery. This review is mainly focused on diseases
      which may present as acute abdomen but for which surgery is usually not
      indicated, such as acute pancreatitis. Furthermore, one also has to consider rare
      diseases in which laparotomy would clearly be a mistake, such as acute
      intermittent porphyria or intestinal pseudo-obstruction.

PMID- 15965665
TI  - [Palliative pain therapy, cannabinoids].
AB  - Cancer pain treatment should follow the recommendations of the World Health
      Organisation. Treatment should be with oral application, regular application
      times and following the analgesic step-ladder. Non-opioids such as dipyrone or
      non-steroids are used for slight to moderate pain, step-2 opioids such as
      tramadol or tilidine/naloxone for moderate pain and step-3 opioids such as
      morphine, oxycodone or hydromorphone for severe pain. Transdermal application of
      fentanyl or buprenorphine offer a non-invasive parenteral alternative for
      patients with stable pain syndromes. Cannabinoids such as tetrahydrocannabinol
      offer a valuable add-on option for cancer patients with refractory pain,
      spasticity, nausea or appetite loss.

PMID- 15965667
TI  - Craniopharyngiomas of childhood: the CHLA experience.
AB  - OBJECTIVE: To improve the outcome of children with craniopharyngiomas by
      analyzing how they were treated. METHODS: The records of patients who underwent
      operation at Childrens Hospital of Los Angeles (CHLA) from 1993 to 2004 were
      reviewed. RESULTS: Identified were 19 girls and 16 boys with an age range from 9
      days to 16 years (mean 7 years, mode 3 years). Tumor control was achieved in 34
      of 35 patients and was accomplished with reasonable outcome in terms of
      neurological deficits and overall level of function. In 25 patients, complete
      tumor resection was obtained with surgery alone, 18 with the first resection, and
      7 with repeat operative intervention. Nine children received radiation therapy
      after the first or second recurrence. On retrospective review, there were no
      consistently identifiable features that would lead one to determine
      preoperatively which tumors would fall into a given category. CONCLUSION: We
      believe that the surgeon must determine a preoperative plan that maximizes the
      chance for a gross total removal of the craniopharyngioma. The biggest challenge
      intraoperatively is to determine whether to continue with the attempt at gross
      total removal or stop short of that goal before producing a significant
      irreversible neurological deficit. A staged removal using different operative
      corridors also needs to be considered.

PMID- 15965666
TI  - Do glucose transporters have other roles in addition to placental glucose
      transport during early pregnancy?
AB  - Human placenta regulates the transport of maternal molecules to the fetus. It is
      known that glucose transport occurs via glucose transporters (GLUTs) in the feto
      placental unit. Data on the expression of GLUTs during implantation are very
      scarce. Moreover, the question of how the decidual leukocytes obtain the energy
      for their activation during implantation mechanism is still under investigation.
      We studied the distributions of GLUT1, GLUT3, and GLUT4 in tissue sections of
      first trimester pregnancies the human maternal-fetal interface. GLUT1 was present
      in apical microvilli of the syncytiotrophoblast, in cytotrophoblast, and in
      vascular patterns of the villous core, whereas GLUT3 was localized in
      cytotrophoblasts of placental villi and in some fetal endothelial cells.
      Moreover, the proliferating cells of the proximal cell columns were also
      immunopositive for GLUT1 and GLUT3. We did not observe any positive
      immunoreactivity for GLUT4 in placental and decidual tissues. Essentially, GLUT3
      and also to some extent GLUT1 was present in maternal leukocytes and platelets.
      In conclusion, our results suggest that the glucose taken up via GLUT1 and GLUT3
      from the maternal circulation might not only be needed for placental functions
      but also for successful implantation by trophoblast invasion, proliferation and
      also by having a role to support energy for maternal leukocytes.

PMID- 15965668
TI  - Craniopharyngioma: a personal (Boston) experience.
AB  - BACKGROUND: The author reports his experience with 79 craniopharyngiomas operated
      since 1988. The review demonstrates that the biological behavior of these tumors
      is extremely variable, and that surgical management requires resourcefulness,
      judgement, and flexibility in the operating room. RESULTS: Tumors will recur
      after total resection (15% in this series) and after subtotal resection and
      radiation therapy (22%) and adjuvant treatments of all types, and no treatment
      guarantees a cure. CONCLUSION: The invasiveness of the tumor leads to difficult
      to-treat long-term complications, particularly obesity and behavior disturbances.
      An extremely long-term follow-up of up to 20 years is necessary in many patients
      in order to determine the ultimate outcome of treatment.

PMID- 15965669
TI  - The pathogenesis of craniopharyngiomas.
AB  - OBJECTIVE: The objective of the study is to review the pathogenesis of
      craniopharyngiomas. METHODS: A literature review of articles relating to the
      embryogenesis of the pituitary gland and sella and the pathogenesis of
      craniopharyngiomas was performed. CONCLUSIONS: Craniopharyngiomas are benign,
      epithelial neoplasms of the sella and parasellar region seen in children and
      adults that may arise from neoplastic transformation of ectoderm-derived
      epithelial cell remnants of Rathke's pouch and the craniopharyngeal duct.

PMID- 15965671
TI  - Surgical excision of neovascularization in retinal angiomatous proliferation.
AB  - BACKGROUND: We report the postoperative outcomes of surgical neovascularization
      excision in patients with retinal angiomatous proliferation (RAP). METHODS: Nine
      eyes of eight patients with RAP who underwent surgical excision of
      neovascularization were studied. Surgical indications were as follows: RAP
      diagnosed by fluorescein and indocyanine green angiography, foveal or perifoveal
      neovascularization, preoperative visual acuity of 0.1 or less, Yannuzzi's stage
      II with detachment of retinal pigment epithelium (RPE) or stage III, and leakage
      on late-phase fluorescein angiography. After cataract surgery, vitreous surgery
      and neovascularization excision were conducted, followed by fluid-air or fluid
      gas exchange. RESULTS: Visual acuity was 0.02-0.1 before surgery and 0.03-0.2
      after surgery. Macular hole formation was seen in one eye but did not lead to
      retinal detachment. In two eyes, subretinal bleeding occurred during excision
      leading to vitreous bleeding after surgery. Although defects of the RPE and
      choriocapillaries were observed after surgery, the exudation and bleeding were
      absorbed. CONCLUSIONS: In stage II RAP cases with RPE detachment, surgical
      excision maintains constant postoperative visual acuity but results in defects of
      RPE and choriocapillaris; therefore, other treatment options should be examined.
      Surgical excision of stage III RAP seems to be promising, as postoperative visual
      acuity remains stable after neovascularization removal in those advanced
      pathologic situations.

PMID- 15965670
TI  - Clinical value of dacryoscintigraphy using a simplified analysis.
AB  - PURPOSE: To study the discriminatory ability of dacryoscintigraphy in
      differentiating between patients with epiphora and volunteers using a simple
      method. METHODS: Twenty eyes in ten volunteers and 66 eyes in 55 patients with
      severe epiphora were studied. Dacryoscintigraphy (15 frames of 1 min) was
      performed after administration of 4 MBq (99m)Tc-pertechnetate (10 mul) in both
      eyes. By mapping a single region of interest (ROI) over the conjunctival sac we
      determined T1 (%dose in first minute) and linear clearance rate (LCR, defined as
      [see text] from the tracer disappearance curve. Reproducibility was determined in
      volunteers. Conjunctival resorption was determined from completely obstructed
      systems. Sensitivity and specificity were calculated and receiver operating
      characteristics (ROC) analysis was conducted. RESULTS: In volunteers mean T1 was
      52.8+/-11.9% (95% CI 47.1-58.4%), and LCR was 74.2+/-11.1% (95% CI 69.0-79.4%).
      Reproducibility was good (mean difference 4.1+/-13.3% for T1 and 0.7+/-17% for
      LCR). Epiphora patients had clearly higher T1 (82.1+/-15.2%, P<0.0001) and lower
      LCR (38.9+/-22.5%, P<0.0001) values. Tracer resorption was 24%. Based on ROC
      analysis 70% for T1 and 50% for LCR were considered optimal cut-off levels to
      separate patients from volunteers. Sensitivity/specificity were 77/95% for T1 and
      71/100% for LCR. T1 and LCR values did not correlate with symptom scores or Anel
      test results. CONCLUSION: Dacryoscintigraphy, using LCR and T1 as parameters, is
      a reliable and objective method to detect tear-flow abnormalities.

PMID- 15965672
TI  - Traumatic globe rupture following penetrating keratoplasty.
AB  - PURPOSE: To evaluate the mechanism, clinical characteristics, management and
      visual outcome of ocular trauma following penetrating keratoplasty (PK). METHODS:
      Twenty-six patients (13 men, 13 women) who suffered surgical wound dehiscence
      after PK because of ocular blunt trauma between 1994 and 2001 were included in
      this retrospective study. Graft dehiscence was managed with primary wound closure
      in all patients. Visual acuity, intraocular pressure, and funduscopy were
      evaluated in the follow-up. RESULTS: The mean age at trauma was 50+/-24 years
      (range 9-88 years). Mean interval between transplantation and trauma was 45.5+/
      64 months (range 1 month to 20 years). Globe rupture occurred at the graft-host
      junction in all patients. Nine of 13 phakic eyes (69.2%) presented lens
      expulsion. Eight of nine pseudophakic eyes (88.9%) had lost their implants.
      Retinal detachment occurred in seven eyes (27%) within 3 months following the
      trauma. Five patients (19.2%) underwent vitreous surgery for posterior segment
      damage. Two eyes (7.7%) were regrafted. At the last examination, only seven eyes
      (27%) had visual acuity of 20/200 or better. CONCLUSIONS: Traumatic wound
      dehiscence may occur, and the prognosis is poor after the injury. Globe rupture
      at the graft-host junction showed persistence of wound weakness even a long time
      after PK. Prevention of ocular trauma should be performed following PK.

PMID- 15965673
TI  - Efficacy and safety of 0.18% sodium hyaluronate in patients with moderate dry eye
      syndrome and superficial keratitis.
AB  - BACKGROUND: Sodium hyaluronate (SH) is used in patients with dry eye. We
      evaluated the efficacy and safety of SH and carboxymethylcellulose (CMC) in the
      treatment of dry eye syndrome with superficial keratitis. METHODS: A total of 22
      patients with moderate dry eye and superficial keratitis were enrolled in a
      prospective, randomised, masked-observer, parallel-group, single-centre study.
      Patients were randomly assigned to a 0.18% SH or 1% CMC solution for a 2-month
      period. In addition to the commonly assessed parameters in patients with dry eye
      (among others symptoms and corneal staining with fluorescein), flow cytometry
      analysis of CD44, HLA DR expressions in impression cytology was investigated as a
      potential efficacy parameter. RESULTS: Both treatments improved the symptoms and
      ocular surface and were well tolerated. SH significantly (p<0.05) decreased CD44
      values compared with CMC. Comfort was significantly (P<0.05) better in the SH
      group than that in the CMC group throughout the study. Recovery in keratitis
      (type, extent and depth) and symptoms were faster in the SH group than in the CMC
      group. Blurred vision was reported by patients in the CMC group only.
      CONCLUSIONS: SH was well tolerated and tended to show a faster efficacy than did
      the CMC-based formulation in patients with moderate dry eye and superficial
      keratitis. SH could therefore advantageously be prescribed from the early stages
      of dry eye disease. This study also showed that flow cytometry in impression
      cytology specimens is a reliable tool for exploring the ocular surface at the
      epithelial level and that CD44, in addition to HLA DR, could be an interesting
      endpoint for future trials in dry eye syndrome with products based on SH.

PMID- 15965674
TI  - Electronic recording of occlusion treatment for amblyopia: potential of the new
      technology.
AB  - BACKGROUND: Approximately one third of all amblyopic eyes do not reach visual
      acuity of 20/40 in spite of occlusion therapy. One of the reasons is a lack of
      adherence to therapy, which, however, could not be quantified in the past.
      Experience with new devices (occlusion dose monitors, ODMs) for electronic
      recording of occlusion has recently been reported. The aim of the present study
      was to evaluate the potential of the ODMs developed in The Netherlands. Various
      features were tested, including the reliability of the ODM recordings compared to
      diaries, two ODMs used simultaneously on one patch, the influence of the ambient
      temperature, and the specificity of the recording pattern for measurements on the
      eye. METHODS: The ODMs were taped to the outside of the standard occlusion patch
      and measured the temperature difference between their front and back surfaces.
      Members of the research group and the families of two patients kept occlusion
      diaries while using the ODMs. Recorded and written occlusion periods were
      compared. Measurements were carried out under various conditions: patch with one
      ODM tightly on the eye or detached (allowing peeping); ODMs taped to various
      parts of the body; two ODMs simultaneously on one patch; variation of room
      temperature. RESULTS: There was good correspondence between the occlusion times
      recorded by the ODMs and those from the diaries, as well as between the
      recordings of two ODMs used simultaneously on one patch. High ambient
      temperatures (33 degrees C to 37 degrees C) prevented reliable ODM measurements.
      Measurements on other parts of the body were misclassified with probabilities
      between P=0.099 and P=0.325 as measurements with the patch tightly on the eye.
      CONCLUSIONS: In spite of some technical limitations, the ODMs provide a chance
      for reliable assessment of compliance and therefore objective information on dose
      response function for occlusion therapy. This will lead to a more evidence-based
      treatment for amblyopia.

PMID- 15965675
TI  - Indocyanine green angiography and fluorescein angiography of malignant choroidal
      melanomas following proton beam irradiation.
AB  - BACKGROUND: The vascularisation features of intraocular tumours may be
      characterised by indocyanine green angiography (ICG-A) and fluorescein
      angiography (FA). Proton beam irradiation is an established method of treating
      malignant melanoma of the choroid. The aim of this study was to describe the
      vascularisation features of small choroidal melanomas and to examine the
      influence of proton beam irradiation on these tumours. METHODS: We examined 39
      choroidal melanomas by ICG-A and FA from 1998 to 2001 in a prospective study. The
      tumours had a mean prominence of 3.65 mm (1.2-7.5 mm) and a common feature of all
      was their parapapillary or paramacular localisation. Angiography was always
      performed immediately before proton beam radiotherapy and at intervals of 3
      months, half a year and 1 year thereafter. Two hundred and forty angiographies
      were analysed in total. RESULTS: Intra-tumoral vessels could be visualised in 89%
      of all tumours by ICG angiography but in only 33% by FA. Neither ICG-A nor FA
      detected changes 3 months after irradiation; however, ICG-A disclosed strong
      leakage from vessels in the tumour area after 6 months. These changes increased
      markedly after 12 months and were also visible by FA. A disadvantage of FA,
      however, was the faster escape of dye from the vessels, which caused rapid
      leakage in the tumour area and meant that details could no longer be
      demonstrated. CONCLUSIONS: ICG-A and FA detect marked vascular changes within the
      tumours examined.

PMID- 15965676
TI  - Perfluorocarbon-perfused vitrectomy: a new method for vitrectomy--a safety and
      feasibility study.
AB  - PURPOSE: To evaluate the safety and feasibility of perfluorocarbon-perfused
      vitrectomy (PCPV) as a technique during vitrectomy for proliferative diabetic
      retinopathy (PDR) and rhegmatogenous retinal detachment (RRD). METHODS: In an
      experimental, prospective, noncomparative and interventional study, 28 eyes of 28
      patients were submitted to vitrectomy with the PCPV technique, 18 eyes with PDR
      and 10 with RRD. In this technique we replaced the traditional balanced saline
      solution (BSS) in the infusion line (conventional vitrectomy) by perfluorocarbon
      liquids (PCL). Some patients with PDR were treated with oxygenated PCL. Clinical
      evaluation, electroretinography (ERG), and endothelial cell count (ECC) were used
      to assess the safety of this procedure. An arbitrary grading system (grades 0-5)
      was used to classify the surgery and maneuvers to assess feasibility. RESULTS: No
      eyes had a significant decrease in ECC, and the patients in whom we could obtain
      ERG postoperatively showed no significant differences from preoperative ERG. In
      the PDR group (using oxygenated and nonoxygenated PCL), 77.8% were graded 5/5; in
      the RRD group 90% were 5/5. PCPV allowed better visualization of vitreous and
      intraocular structures, rapid retinal reattachment, less blood in the vitreous
      cavity, subretinal fluid resolution, blood confinement, retinal stabilization,
      and easier dissection of epiretinal membranes. In all cases at least one surgical
      step was eliminated. CONCLUSIONS: PCPV in humans is a safe and feasible
      technique. Probably in selected cases the use of PCL offers several advantages
      over BSS, because of their properties (gravitational forces, immiscibility with
      bodily fluids, and ability to transport oxygen). Prospective and comparative
      studies are necessary to establish formal indications and possible
      contraindications.

PMID- 15965677
TI  - Chemical shift imaging and localised magnetic resonance spectroscopy in full-term
      asphyxiated neonates.
AB  - BACKGROUND: Diagnosis of brain lesions after birth anoxia-ischemia is essential
      for appropriate management. Clinical evaluation is not sufficient. MRI has been
      proven to provide useful information. OBJECTIVE: To compare abnormalities
      observed with MRI, including diffusion-weighted imaging (DWI), localised magnetic
      resonance spectroscopy (MRS) and chemical shift imaging (CSI) and correlate these
      findings with the clinical outcome. MATERIALS AND METHODS: Fourteen full-term
      neonates with birth asphyxia were studied. MRI, MRS and CSI were performed within
      the first 4 days of life. RESULTS: Lesions observed with DWI were correlated with
      outcome, but the apparent diffusion coefficient (ADC) did improve diagnostic
      confidence. The mean value of Lac/Cr for the neonates with a favourable outcome
      was statically lower than for those who died (0.22 vs 1.04; P = 0.01). The same
      results were observed for the Lac/NAA ratio (0.21 vs 1.23; P = 0.01). Data
      obtained with localised MRS and CSI were correlated for the ratio N-acetyl
      aspartate/choline, but not for the other metabolites. No correlation was found
      between the ADC values and the metabolite ratios. CONCLUSIONS: Combination of
      these techniques could be helpful in our understanding of the physiopathological
      events occurring in neonates with asphyxia.

PMID- 15965678
TI  - Iliac hyperdense line: a new radiographic sign of gluteal muscle contracture.
AB  - BACKGROUND: A hyperdense line on the ilium that runs roughly parallel to the
      sacroiliac joint (we called it "iliac hyperdense line sign") was frequently
      observed on pelvic radiographs of patients with gluteal muscle contracture (GMC).
      A literature search revealed no description of this sign. OBJECTIVE: To determine
      the relationship between the iliac hyperdense line sign and GMC and to explore
      how this sign is formed. MATERIALS AND METHODS: Pelvic plain films of 103 cases
      of GMC and those of 200 control individuals were reviewed for the presence or
      absence of the iliac hyperdense line sign. Pelvic CT scans in 8 of 103 cases and
      13 of 200 controls were analyzed with relation to the plain films. RESULTS: The
      iliac hyperdense line sign was visualized in 85 of 103 (82.5%) cases of GMC and
      none of the 200 controls. In the GMC group, pelvic CT scans showed a deformity of
      the posterior ilium. The lateral cortex of the posterior ilium took on a partly
      or completely anteroposterior course, while in the control group the course
      appeared as an oblique orientation from posteromedial to anterolateral.
      CONCLUSION: The iliac hyperdense line on pelvic plain film can be used as a
      radiographic sign to suggest a diagnosis of GMC. This sign might be a result of
      the long and persistent pulling effect of the contracted gluteus maximus muscle,
      which deforms the lateral cortex of the posterior ilium from an oblique course to
      an anteroposterior course tangential to the X-ray beam.

PMID- 15965680
TI  - [On the status of the new generation of traumatic surgeons. Results of a survey
      of the young forum within the DGU].

PMID- 15965679
TI  - Plastid transformants of tomato selected using mutations affecting ribosome
      structure.
AB  - Tomato plastid transformants were obtained using two vectors containing cloned
      plastid DNA of either Nicotiana tabacum or Solanum nigrum and including point
      mutations conferring resistance to spectinomycin and streptomycin. Transformants
      were recovered after PEG-mediated direct DNA uptake into protoplasts, followed by
      selection on spectinomycin-containing medium. Sixteen lines contained the point
      mutation, as confirmed by mapping restriction enzyme sites. One line obtained
      with each vector was analysed in more detail, in comparison with a spontaneous
      spectinomycin-resistant mutant. Integration of the cloned Solanum or Nicotiana
      plastid DNA, by multiple recombination events, into the tomato plastome was
      confirmed by sequence analysis of the targeted region of plastid DNA in the
      inverted repeat region. Maternal inheritance of spectinomycin and streptomycin
      resistances or sensitivity in seedlings also confirmed the transplastomic status
      of the two transformants. The results demonstrate the efficacy in tomato of a
      selection strategy which avoids the integration of a dominant bacterial
      antibiotic resistance gene.

PMID- 15965681
TI  - [Introduction to the topic: How much hydrocortisone does the patient really need?
      The (anti-)stress hormone in the perioperative phase].

PMID- 15965682
TI  - Thyroid function and outcome in children who survived meningococcal septic shock.
AB  - OBJECTIVE: To investigate the time course of thyroid function, factors that
      affect it, and its relationship to outcome in children surviving meningococcal
      septic shock. DESIGN AND SETTING: Observational cohort study in a university
      affiliated pediatric intensive care unit (PICU). PATIENTS AND PARTICIPANTS: We
      divided the 44 children admitted to the PICU who survived meningococcal septic
      shock into those with short-stay (<7 days, n=33) or long-stay (>or=7 days, n=11).
      MEASUREMENTS AND RESULTS: Serum thyroid hormone concentrations were determined on
      PICU admission and after 24 and 48 h. The Pediatric Risk of Mortality score and
      selected laboratory parameters were used to assess disease severity. On admission
      all children showed signs of euthyroid sick syndrome: low total triiodothyronine
      (TT3) and high reverse triiodothyronine (rT3) without compensatory elevated
      thyrotropin (TSH). Admission rT3 levels and the TT3/rT3 ratio were correlated
      with C-reactive protein levels and with time from first petechia to admission.
      Short-stay children only had higher TT3 and lower interleukin 6 levels at
      admission than long-stay children; after 48 h they showed higher total thyroxin,
      free thyroxin, TT3, and TSH and lower rT3 than long-stay children. All changes in
      thyroid parameters within the first 24 h were related to length of PICU stay. In
      children receiving dopamine TSH levels and TT3/rT3 ratios remained unchanged,
      whereas both values increased in those who did not receive dopamine or in whom
      dopamine was discontinued. CONCLUSIONS: All children surviving meningococcal
      septic shock showed signs of euthyroid sick syndrome on admission. Thyroid
      hormone level changes in the first 24 h were prognostic for length of PICU stay.

PMID- 15965683
TI  - A capillary electrophoresis chip with hydrodynamic sample injection for
      measurements from a continuous sample flow.
AB  - A microchip-based capillary electrophoresis device supported by a microfluidic
      network made of poly(dimethylsiloxane), used for measuring target analytes from a
      continuous sample flow, is presented. The microsystem was fabricated by means of
      replica molding in combination with standard microfabrication technologies,
      resulting in microfluidic components and an electrochemical detector. A new
      hydrodynamic sample injection procedure is introduced, and the maximum number of
      consecutive measurements that can be made with a poly(dimethylsiloxane) capillary
      electrophoresis chip with amperometric detection is investigated with respect to
      reproducibility. The device features a high degree of functional integration, so
      the benefits associated with miniaturized analysis systems apply to it.

PMID- 15965684
TI  - Determination of cadmium in coal using solid sampling graphite furnace high
      resolution continuum source atomic absorption spectrometry.
AB  - This work describes the development of a method to determine cadmium in coal, in
      which iridium is used as a permanent chemical modifier and calibration is
      performed against aqueous standards by high-resolution continuum source atomic
      absorption spectrometry (HR-CS AAS). This new instrumental concept makes the
      whole spectral environment in the vicinity of the analytical line accessible,
      providing a lot more data than just the change in absorbance over time available
      from conventional instruments. The application of Ir (400 microg) as a permanent
      chemical modifier, thermally deposited on the pyrolytic graphite platform
      surface, allowed pyrolysis temperatures of 700 degrees C to be used, which was
      sufficiently high to significantly reduce the continuous background that occurred
      before the analyte signal at pyrolysis temperatures <700 degrees C. Structured
      background absorption also occurred after the analyte signal when atomization
      temperatures of >1600 degrees C were used, which arose from the electron
      excitation spectrum (with rotational fine structure) of a diatomic molecule.
      Under optimized conditions (pyrolysis at 700 degrees C and atomization at 1500
      degrees C), interference-free determination of cadmium in seven certified coal
      reference materials and two real samples was achieved by direct solid sampling
      and calibrating against aqueous standards, resulting in good agreement with the
      certified values (where available) at the 95% confidence level. A characteristic
      mass of 0.4 pg and a detection limit of 2 ng g(-1), calculated for a sample mass
      of 1.0 mg coal, was obtained. A precision (expressed as the relative standard
      deviation, RSD) of <10% was typically obtained when coal samples in the mass
      range 0.6-1.2 mg were analyzed.

PMID- 15965685
TI  - High-resolution gas chromatography retention data as a basis for estimation of
      the octanol-water distribution coefficients (Kow) of PCB: the effect of
      experimental conditions.
AB  - The semi-experimental approach to approximating physicochemical data relevant to
      environmental distribution (vapor pressure and gas-octanol distribution) by
      correlation with gas chromatography (GC) retention data has been extended to the
      determination of Kow values. We estimated Kow values >10(4) for polychlorinated
      biphenyls (PCB), which are often derived by liquid chromatography, by correlation
      with gas chromatographic retention data. Selecting a set of reference compounds
      with known Kow values for relative retention time (RRT) correlation enables easy
      and accurate semi-empirical calculation of further Kow values for a given group
      of congeners. The RRT/log Kow correlation is validated in this paper with regard
      to the following gas chromatographic conditions: (1) isothermal versus
      temperature-programmed elution, (2) the possible effect of the polarity of the
      stationary phase, and (3) the effect of the format of the standardized GC
      retention data. The advantages of our Kow(GC) method can be summarized as
      follows: complex mixtures can be analyzed, only amounts in the nanogram-range or
      less are required, Kow values of isomers can be determined and the exact
      structure of compounds need not be known. Normalized GC retention data of
      persistent organic pollutants are readily available. The quality of the Kow
      values obtained by the GC method compares well with that for other Kow estimation
      methods. It depends mainly on the accuracy of the Kow data of the structurally
      correlated compounds used as standards for the correlation cohort. The Kow(GC)
      data for all 209 PCB congeners are given.

PMID- 15965686
TI  - Thermostability of landscape phage probes.
AB  - Immunoassays have traditionally relied on antibodies as diagnostic probes. Their
      use outside of a laboratory, however, may be problematic because antibodies are
      often unstable in severe environmental conditions. Environmental monitoring
      requires thermostable probes, such as landscape phage, that carry thousands of
      foreign peptides on their surfaces, are superior to antibodies, and can operate
      in non-controlled conditions. While parent wild-type phage are known to be
      extremely stable in various media at high temperatures, no work has been done to
      demonstrate the stability of landscape phage probes. We examined the
      thermostability of a landscape phage probe and a monoclonal antibody specific for
      beta-galactosidase in parallel in an enzyme-linked immunosorbent assay (ELISA)
      format. They were both stable for greater than six months at room temperature,
      but at higher temperatures the antibody degraded more rapidly than the phage
      probe. Phage retained detectable binding ability for more than six weeks at 63
      degrees C, and three days at 76 degrees C. The activation energy of phage
      degradation was determined to be 1.34 x 10(5) J/mol. These results confirm that
      phage probes are highly thermostable and can function even after exposure to high
      temperatures during shipping, storage and operation.

PMID- 15965687
TI  - Early restaging whole-body (18)F-FDG PET during induction chemotherapy predicts
      clinical outcome in patients with locoregionally advanced nasopharyngeal
      carcinoma.
AB  - PURPOSE: This study was undertaken to evaluate the utility of whole-body (18)F
      FDG PET in monitoring therapeutic effect during induction chemotherapy (IC) and
      in predicting prognosis in patients with locoregionally advanced nasopharyngeal
      carcinoma (NPC). METHODS: Fifty patients who had histologically proven,
      locoregionally advanced NPC without distant metastasis and had received IC were
      recruited in this study. The study cohort consisted of 19 females and 31 males
      (age 17-72 years, mean 45.9+/-11.9). Whole-body (18)F-FDG PET was performed in
      each patient after completion of one (33 patients) or two (17 patients) courses
      of IC. Each patient was restaged on the basis of the (18)F-FDG PET results.
      Patients who were downstaged to stage I or II were classified as major
      responders; the rest were classified as non-major responders. RESULTS: Only 1 of
      the 23 major responders subsequently developed local recurrence. At the time of
      data analysis, all major responders were alive; by contrast, of the 27 non-major
      responders, 15 had locoregional recurrence or distant metastasis and nine had
      died (seven of NPC and two of treatment-related complications). Kaplan-Meier
      survival analysis showed significantly longer recurrence-free survival and
      overall survival in major responders (56.4+/-9.2 and 58.1+/-2.2 months) as
      compared with non-major responders (33.7+/-23.2 and 44.7+/-20.0 months), with
      p<0.0001 and p=0.0024, respectively. CONCLUSION: The results of this study
      suggest that early restaging by a single whole-body (18)F-FDG PET scan after the
      first or second course of IC is useful for predicting therapeutic response and
      outcome in patients with locoregionally advanced NPC.

PMID- 15965688
TI  - Prospective bone density changes after periacetabular osteotomy: a methodological
      study.
AB  - We used computed tomography (CT) and 3D design-based sampling principles
      (stereology) to estimate changes in acetabular bone density after periacetabular
      osteotomy. We included six consecutive patients with hip dysplasia in the study.
      Baseline density was measured within the first 7 days following periacetabular
      osteotomy and compared with bone density 2 years later. Double measurements were
      performed on three patients, and the coefficient of error of the mean was
      estimated to 0.05. Bone density in zone 1 increased significantly in the
      anteromedial quadrant as well as in the posteromedial quadrant of the acetabulum.
      In the anterolateral and the posterolateral quadrant, bone density was unchanged.
      In zone 2 and 3, bone density was unchanged 2 years postoperatively. We suggest
      that the observed increase in bone density medially represents a remodelling
      response to an altered load distribution after osteotomy. The method used is a
      precise tool to estimate changes in acetabular bone density.

PMID- 15965689
TI  - Revision of the Sheehan total knee arthroplasty.
AB  - The use of the Sheehan knee prosthesis extended from 1971 to 2002. It
      incorporated a semi-constrained hinge with intra-medullary stems cemented into
      the femur and tibia. While some authors have reported excellent short-term
      results, others have reported revision rates of up to 31% at 5--10 years. The aim
      of this study was to review the senior author's experience in revising these
      arthroplasties. We review 54 Sheehan total knee replacements and discuss the
      difficulties encountered during first and subsequent revisions and the often
      complex reconstruction techniques used to overcome these.

PMID- 15965690
TI  - Focal nodular hyperplasia in a child with Beckwith-Wiedemann syndrome.
AB  - Beckwith-Wiedemann Syndrome (BWS) is associated with somatic overgrowth and a
      high risk for embryonal tumors, including hepatoblastoma, a highly malignant
      liver tumor of childhood. Focal nodular hyperplasia (FNH), on the other hand, is
      a benign tumor of the liver that is uncommon in childhood. Herein we describe a
      case of FNH in a child with BWS, the first such report in the literature.

PMID- 15965691
TI  - Recurrent acute pancreatitis caused by malrotation of the intestine and effective
      treatment with laparoscopic Ladd's procedure.
AB  - We herein report a rare case of recurrent pancreatitis caused by malrotation of
      the intestine. Since the age of 10 years, a female patient showed recurrent
      epigastralgia and was diagnosed at age 16 years as suffering from acute
      pancreatitis. Upper gastrointestinal series showed that the duodenal bulb was
      elongated and rotated caudally. Endoscopic retrograde cholangiopancreatography
      showed that the descending portion of the duodenum was rotated and occluded the
      papilla of Vater. Under laparoscopy, the duodenal bulb was tracted caudally by
      the Ladd's ligament. By incision of this ligament, the entire duodenum was
      mobilized, with subsequent reduction of the rotation and compression of the
      pancreatic head. The girl's postoperative course was uneventful, and she has been
      asymptomatic for the last 3 years. In conclusion, malrotation of the intestine
      may be a rare cause of recurrent pancreatitis, and laparoscopic Ladd's procedure
      may be a less invasive and useful treatment.

PMID- 15965692
TI  - Use of vacuum-assisted closure system in the management of complex wounds in the
      neonate.
AB  - The vacuum-assisted closure (VAC) system has become an accepted treatment
      modality for acute and chronic wounds in adults. The use of negative-pressure
      dressing has been documented in adults and, to some extent, in children. However,
      its use in premature infants has not been reported in the literature. The results
      of using the VAC system were examined in two premature infants with complex
      wounds. The VAC system was found to be effective in facilitating the closure of
      large and complex wounds in these patients. Complete epithelialization of the
      wounds was achieved in both patients without skin grafting. In conclusion, in two
      premature neonates with extraordinary soft tissue defects, the VAC system was a
      safe and effective choice to assist in closing these wounds.

PMID- 15965693
TI  - Congenital ureteric strictures: an uncommon cause of antenatally detected
      hydronephrosis.
AB  - Often misdiagnosed as primary megaureter or pelviureteric junction obstruction,
      congenital ureteral stenosis and valves are the main causes of congenital
      ureteric obstruction. We report three consecutive cases of congenital ureteric
      strictures presenting with antenatally diagnosed hydronephrosis. Two of our cases
      had a contralateral multicystic dysplastic kidney. We discuss the aetiology,
      clinical presentation, diagnostic evaluation, surgical management, and operative
      results as well as present an overview of the international literature,
      highlighting the importance of early referral in cases of contralateral
      abnormality as well as the importance of performing a retrograde study to
      facilitate the diagnosis and choice of incision.

PMID- 15965694
TI  - Diphallus with ectopic bowel segment: a case report.
AB  - A 1-year-old boy presented with complete duplication of the penis, with an
      ectopic bowel segment as an associated anomaly. The boy had duplicated epispadiac
      urethras. The right one ended blindly whereas the left one was patent, leading
      into the bladder. There was separation of the symphysis pubis and bifid scrotum.
      Investigations revealed no other anomalies. A review of the literature concerning
      diphallus showed a preponderance of associated anomalies such as exstrophy,
      bladder duplication, ureteral or renal defects, and imperforate anus, but no
      cases with an ectopic bowel segment. We report this case because of its extreme
      rarity.

PMID- 15965695
TI  - Hypertrophic pyloric stenosis in twins: same genes or same environments?
AB  - The aetiology of infantile hypertrophic pyloric stenosis (IHPS) remains obscure.
      Cases in twins, usually monozygotic, have been sporadically reported as evidence
      for the genetic origin of the disease. We present a case of IHPS in a pair of
      dizygotic male twins together with a review of the literature, focusing on the
      question of whether the twin cases actually support a genetic or an acquired
      nature of IHPS.

PMID- 15965696
TI  - Vaginal metastasis revealing colon adenocarcinoma.

PMID- 15965697
TI  - Frontotemporal dementia, motor neuron disease and tauopathy: clinical and
      neuropathological study in a family.
AB  - We report a familial disorder occurring in three patients that presented as
      frontotemporal dementia (FTD). A neuropathological study was performed in a 58
      year-old patient, who developed FTD 2 years prior to the onset of motor neuron
      disease (MND), and died at age 62. Lesions indicative of associated MND were
      observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies,
      axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased
      neuronal density and laminar microvacuolation of layers II and III in the frontal
      and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the
      spinal cord and medulla, but were absent from the temporal and frontal cortex.
      There were also widespread deposits of various neuronal and glial inclusions
      containing abnormally phosphorylated tau protein, the Western blotting pattern of
      which was characterized by two major bands of 64 and 69 kDa. There were no
      abnormalities of the entire coding sequences of microtubule-associated protein
      tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results
      suggest that FTD associated with MND can be caused by a larger spectrum of
      neuropathological lesions than commonly accepted.

PMID- 15965698
TI  - Distribution of cerebral cortical lesions in diffuse neurofibrillary tangles with
      calcification: a clinicopathological study of four autopsy cases showing
      prominent parietal lobe involvement.
AB  - We investigated clinicopathologically four Japanese autopsy cases of diffuse
      neurofibrillary tangles with calcification (DNTC), which has been believed to be
      characterized by temporal or temporofrontal circumscribed lobar atrophy, and
      examined the distribution of their cerebral cortical lesions using hemisphere
      specimens. The lesions were classified into three categories (slight, moderate,
      and severe). Severe lesions were present in the temporal lobes and insular gyri
      of all four cases, consistent with the studies reported to date. In contrast,
      severe lesions were encountered in the parietal lobe of case 1 and moderate
      lesions were found in the parietal lobes of cases 2-4. Furthermore, moderate
      lesions of the precentral gyrus were present in cases 2-4, and moderate lesions
      of the postcentral gyrus were encountered in all four cases. We postulate that
      the distribution of cerebral cortical lesions in DNTC is more widespread than
      previously assumed. Our data also indicate that the unusual clinical signs of
      DNTC reported by several Japanese researchers, including parietal signs such as
      apraxia and agnosia, are roughly consistent with the topographic distribution of
      cerebral cortical lesions in DNTC elucidated in this study.

PMID- 15965699
TI  - Neuropathological spectrum of cortical dysplasia in children with severe focal
      epilepsies.
AB  - Cortical dysplasias comprise a variable spectrum of clinical, neuroradiological
      and histopathological findings. We report about a cohort of 25 pediatric patients
      (mean age 8.1+/-4.8 years) with severe drug-resistant early onset focal
      epilepsies (mean duration 2.1+/-0.4 years), mental/psychomotor retardation, and
      multilobar epileptogenesis. Compared to age-matched biopsy controls,
      microscopical inspection of neurosurgically resected specimens revealed
      dysplastic neurons with/without balloon cells in only 7 patients. According to
      Palmini's classification system, these lesions were categorized as focal cortical
      dysplasia (FCD) type II. All other patients presented with rather subtle but
      statistically significant neuroanatomical abnormalities. We identified increased
      numbers of ectopic neurons in white matter and cortical gliosis. However, most
      intriguing was our finding of a microcolumnar arrangement of cortical neurons in
      layer III. These microcolumns can be statistically defined as vertical lining of
      more than eight neurons (two times standard deviation of cell countings obtained
      from controls). In addition, neuronal perikarya were significantly smaller in
      epilepsy patients. Although histological abnormalities occurring during postnatal
      maturation of the brain challenge any neuropathological classification in this
      group of young patients, we propose that these findings are classified according
      to FCD type I. Our observations support a concept compatible with regional loss
      of high-order brain organization.

PMID- 15965700
TI  - Pediatric embryonal tumor of the cerebellum with rhabdoid cells and novel
      intracytoplasmic inclusions: distinction from atypical teratoid/rhabdoid tumor.
AB  - We report a case of embryonal tumor with novel inclusion bodies occurring in the
      cerebellum of a 12-year-old girl. The tumor was histopathologically composed of
      small undifferentiated cells intermingled with a small number of rhabdoid cells,
      which had an ultrastructural feature of intermediate filament whorls.
      Immunohistochemically, the neoplasm showed a polyphenotype, including glial
      fibrillary acidic protein (GFAP), S-100, synaptophysin, chromogranin A,
      cytokeratin, vimentin, smooth muscle actin, and desmin. However, epithelial
      membrane antigen (EMA) immunoreactivity was absent. The MIB-1 labeling index was
      high (25.6%). Ultrastructurally, there was no evidence of neuronal or myogenic
      differentiation. The small neoplastic cells contained numerous small
      intracytoplasmic inclusions stained pink by eosin and red by Masson's trichrome
      stain. The inclusion body was a densely packed, granulovesicular structure at the
      electron microscopic level, and was immunoreactive for vimentin, GFAP, desmin,
      and actin. Reverse transcription-PCR and immunohistochemistry showed the
      expression of INI1 at the RNA and protein levels, respectively. In conclusion,
      this tumor was differentiated from atypical teratoid/rhabdoid tumor by the
      absence of EMA and the presence of INI1 mRNA and protein, and diagnosed as an
      unclassified, embryonal tumor. Eosinophilic, granulovesicular inclusions of the
      tumor cells are novel cytoplasmic inclusions in the brain tumor.

PMID- 15965701
TI  - Results of vancomycin-impregnated cancellous bone grafting for infected tibial
      nonunion.
AB  - INTRODUCTION: Bone grafting plays a critical role in promoting bone healing in
      infected nonunion, although recurrent infection is of concern. Cancellous bone
      grafting as an antibiotic delivery system has been reported as an effective
      method to combat infections. In this study, we report the clinical results of
      vancomycin-impregnated cancellous bone grafting for the treatment of infected
      tibial nonunion. MATERIALS AND METHODS: Between January 1996 and March 2001, 18
      patients with infected tibial nonunion treated with vancomycin-impregnated
      cancellous bone grafting were available for follow-up. According to the Cierny
      Mader classification, all patients belonged to type IVA and IVB osteomyelitis.
      Adequate debridement, stabilization with external fixation, and staged vancomycin
      impregnated cancellous bone grafting were used in all patients. Regular clinical
      and radiographic follow-ups were conducted. RESULTS: Infection control was
      obtained in all 18 patients with a 100% infection arrest rate. Bone union was
      achieved in 13 of 18 patients at an average of 5.8 months. Bone union was
      obtained subsequently in the remaining five patients after closed nailing in
      four, and plating and bone grafting in one patient. Radiographs showed good
      consolidation and hypertrophy of grafted bone at an average follow-up of 48
      months. CONCLUSION: We conclude that vancomycin-impregnated cancellous bone
      grafting is a safe method for the treatment of infected tibial nonunion.

PMID- 15965702
TI  - Quality of pronase dissociation of mature inferior colliculus neurons.
AB  - One major advantage of acutely dissociated inferior colliculus (IC) neurons in
      electrophysiological investigations is their complete isolation from the
      surrounding cellular network. In this way, patch-clamp recordings can be
      performed under controlled conditions to study membrane properties of IC neurons
      in more detail. The aim of the present study was to adapt a dissociation method
      for immature IC neurons to the highly sensitive, fragile and vulnerable mature IC
      neurons of mammals (mice). The modification of a pronase-based dissociation
      protocol with respect to concentration, incubation time and handling
      (trituration) of the cells yielded intact, live IC neurons with a clean cell
      surface so that they were well suited for further electrophysiological
      investigations in our study. The largely modified dissociation protocol is
      described in detail and critically discussed.

PMID- 15965703
TI  - Ossification of the external ear: a case report and review of the literature.
AB  - A rare case of idiopathic bilateral ossification of the auricular cartilage and
      cartilage of the external ear canal is reported. The hardening and thickening of
      the external ear canals with subsequent narrowing and impaired exposure resulted
      in symptomatic hearing loss because of the recurrent impediment of inspissated
      cerumen, the removal of which finally became impossible. Surgical resection of
      the cartilage external ear canal and tragus was indicated to provide a more
      permanent treatment of conductive hearing loss. Histological examination revealed
      complete replacement of the fibroelastic cartilage by normal bone structures
      showing Haversian canals and bone marrow. The present case report is unique
      because of the involvement of both the auricles and external ear canals, the
      symptomatic hearing loss and the surgical treatment to relieve symptoms.

PMID- 15965704
TI  - In-depth sequence analysis of the tomato chromosome 12 centromeric region:
      identification of a large CAA block and characterization of pericentromere
      retrotranposons.
AB  - We sequenced a continuous 326-kb DNA stretch of a microscopically defined
      centromeric region of tomato chromosome 12. A total of 84% of the sequence (270
      kb) was composed of a nested complex of repeat sequences including 27
      retrotransposons, two transposable elements, three MITEs, two terminal repeat
      retrotransposons in miniature (TRIMs), ten unclassified repeats and three
      chloroplast DNA insertions. The retrotransposons were grouped into three families
      of Ty3-Gypsy type long terminal repeat (LTR) retrotransposons (PCRT1-PCRT3) and
      one LINE-like retrotransposon (PCRT4). High-resolution fluorescence in situ
      hybridization analyses on pachytene complements revealed that PCRT1a occurs on
      the pericentromere heterochromatin blocks. PCRT1 was the prevalent
      retrotransposon family occupying more than 60% of the 326-kb sequence with 19
      members grouped into eight subfamilies (PCRT1a-PCRT1h) based on LTR sequence. The
      PCRT1a subfamily is a rapidly amplified element occupying tens of megabases. The
      other PCRT1 subfamilies (PCRT1b-PCRT1h) were highly degenerated and interrupted
      by insertions of other elements. The PCRT1 family shows identity with a
      previously identified tomato-specific repeat TGR2 and a CENP-B like sequence. A
      second previously described genomic repeat, TGR3, was identified as a part of the
      LTR sequence of an Athila-like PCRT2 element of which four copies were found in
      the 326-kb stretch. A large block of trinucleotide microsatellite (CAA)n occupies
      the centromere and large portions of the flanking pericentromere heterochromatin
      blocks of chromosome 12 and most of the other chromosomes. Five putative genes in
      the remaining 14% of the centromere region were identified, of which one is
      similar to a transcription regulator (ToCPL1) and a candidate jointless-2 gene.

PMID- 15965705
TI  - Specific detection and semi-quantitative analysis of TRPC4 protein expression by
      antibodies.
AB  - In mouse tissues two variants of the transient receptor potential (canonical)
      (TRPC) 4 protein are expressed: the "full-length" TRPC4 protein and a slightly
      smaller variant, called TRPC4Delta(761-864), which lacks 84 amino acid residues.
      Although the presence of mRNA encoding the TRPC4 protein in mammalian cells and
      the detection of the heterologously expressed TRPC4 protein by Western blot
      analysis have been reported, the unequivocal detection of endogenous TRPC4
      proteins has proven difficult. In the present study we compared polyclonal
      antibodies for the detection of TRPC4 proteins in mouse tissues and monitored
      their specificity and reliability by analysing corresponding tissues from TRPC4
      deficient mice. In addition we introduced a procedure that allows us to estimate
      the amount of TRPC4 protein expressed in a single cell. Using this technique it
      appears that the amount of TRPC4 protein expressed stably in HEK 293 cells is at
      least fourfold higher than the amount of TRPC4 protein expressed endogenously in
      the bovine adrenocortical cell line SBAC.

PMID- 15965706
TI  - TRPC1: store-operated channel and more.
AB  - Transient receptor potential canonical 1 (TRPC1) is a transmembrane protein
      expressed in a range of vertebrate cells including smooth muscle, endothelium,
      neurones and salivary gland cells. It functions as an element of a mixed cationic
      Ca(2+)-permeable channel, probably commonly as part of a heterotetrameric
      assembly involving other related proteins such as TRPC5. Wide-ranging biological
      roles of TRPC1 are suggested, including regulation of smooth muscle and stem cell
      proliferation, endothelin-evoked arterial contraction, salivary gland secretion,
      endothelial permeability, glutamatergic neurotransmission, growth cone turning,
      neuroprotection, neuronal differentiation, lipid raft integrity and the nuclear
      factor of activated T-cell transcription factor. The mechanisms by which TRPC1
      serves these functions are starting to emerge. At one level, it is apparent that
      TRPC1 is subcellularly compartmentalised, at least in part in cholesterol-rich
      caveolae closely associated with sub-plasmalemmal endoplasmic reticulum. At
      another level, TRPC1 is embedded in a protein complex that can include inositol
      trisphosphate receptor, homer, calmodulin, caveolin-1, FKBP25, I-mfa, MxA,
      GluR1alpha, bFGFR-1, G(q/11) protein, phospholipase C-beta/gamma, protein kinase
      C-alpha and RhoA. It is also apparent that TRPC1 responds to general stimuli-not
      only depletion of intracellular Ca(2+) stores, but also receptor activation, and
      membrane stretch. We are at the early stages of understanding of how these
      various signals and components integrate to form a functional channel, and this
      article provides a brief overview of current progress.

PMID- 15965707
TI  - Can autologous thrombin with a rest fraction of ethanol be used safely for
      activation of concentrated autologous platelets applied on nerves?
AB  - The use of concentrated platelet-rich plasma (cPRP) as a source of growth factors
      is reported to be beneficial for an enhanced osteogenesis in spine surgery. Today
      both bovine and autologous thrombin is used for activating the platelets and thus
      releasing the growth factors. In order to prevent transmission of organisms and
      the development of antibodies, autologous thrombin seems to be the logical
      choice. However, the preparation of autologous thrombin is cumbersome and
      consumes a part of the cPRP. In order to overcome this problem, a commercial
      autologous thrombin kit (activAT, Dideco, a Sorin Group company, Italy) has been
      developed which produces autologous thrombin out of platelet-poor plasma. A
      possible disadvantage of this kit could be the rest fraction of 1.18% of ethanol
      in the platelet gel. In a pig model, the influence of different ethanol
      concentrations on the ischiadic nerve was studied. The study consisted out of
      four groups; a control group (n=6), a group with platelet gel 0% ethanol (n=6), a
      group with platelet gel 1.18% ethanol (n=6) and a group with platelet gel 3.8%
      ethanol (n=7). In all the groups, the ischiadic nerve was dissected and the
      myelin sheet opened after which the wound was closed (control group) or one of
      the three therapies was applied. After 12 h, the animal was sacrificed and the
      ischiadic nerve was submitted for histological examination. Myelin sheaths
      appeared normal in all cases. No axonal swelling was observed. No statistically
      significant differences were observed for neutrophilic and eosinophilic
      infiltration nor for collagen necrosis between groups. Platelet gel prepared by
      the use of a commercial autologous thrombin kit and containing 1.18% of ethanol
      can be safely used on nerves.

PMID- 15965708
TI  - Validation of new clinical quantitative analysis software applicable in spine
      orthopaedic studies.
AB  - The objective of this study was to evaluate an X-ray films analysis software,
      i.e. to estimate the reliability and validity of clinical measurements by means
      of this software. The authors first performed tests of precision and
      reproducibility of measures. The precision for dynamic modules was estimated at
      +/-2 degrees for the lumbar analysis and +/-3 degrees for the cervical one. Mean
      reproducibility coefficients calculated for postural modules are about 4 degrees
      for the angular parameters and 3 mm for the linear ones. We also evaluated
      clinical applicability of the software through its validity. Reference values
      calculated on a population of healthy subjects showed agreement with the
      literature. Then, when analysing postural X-ray films of severe scoliotic
      patients, we found that inter-observer reproducibility coefficients show a lower
      reliability of measurements; the main cause seems to be the low visibility of
      anatomic landmarks due to the quality of X-ray films and to the degree of
      deformity. This study allowed to better estimate the reliability and the
      usefulness of this tool, allowing for multicentric studies and exchanges.

PMID- 15965710
TI  - The formation of neural codes in the hippocampus: trace conditioning as a
      prototypical paradigm for studying the random recoding hypothesis.
AB  - The trace version of classical conditioning is used as a prototypical hippocampal
      dependent task to study the recoding sequence prediction theory of hippocampal
      function. This theory conjectures that the hippocampus is a random recoder of
      sequences and that, once formed, the neuronal codes are suitable for prediction.
      As such, a trace conditioning paradigm, which requires a timely prediction, seems
      by far the simplest of the behaviorally-relevant paradigms for studying
      hippocampal recoding. Parameters that affect the formation of these random codes
      include the temporal aspects of the behavioral/cognitive paradigm and certain
      basic characteristics of hippocampal region CA3 anatomy and physiology such as
      connectivity and activity. Here we describe some of the dynamics of code
      formation and describe how biological and paradigmatic parameters affect the
      neural codes that are formed. In addition to a backward cascade of coding
      neurons, we point out, for the first time, a higher-order dynamic growing out of
      the backward cascade-a particular forward and backward stabilization of codes as
      training progresses. We also observe that there is a performance compromise
      involved in the setting of activity levels due to the existence of three
      behavioral failure modes. Each of these behavioral failure modes exists in the
      computational model and, presumably, natural selection produced the compromise
      performance observed by psychologists. Thus, examining the parametric
      sensitivities of the codes and their dynamic formation gives insight into the
      constraints on natural computation and into the computational compromises ensuing
      from these constraints.

PMID- 15965709
TI  - Correlations between genotype, ultrastructural morphology and clinical phenotype
      in the neuronal ceroid lipofuscinoses.
AB  - The neuronal ceroid lipofuscinoses (NCLs) are a group of severe neurodegenerative
      diseases with onset usually in childhood and characterised by the intracellular
      accumulation of autofluorescent storage material. Within the last decade,
      mutations that cause NCL have been found in six human genes (CLN1, CLN2, CLN3,
      CLN5, CLN6 and CLN8). Mutations in two additional genes cause disease in animal
      models that share features with NCL-CTSD in sheep and mice and PPT2 in mice.
      Approximately 160 NCL disease-causing mutations have now been described (listed
      and fully cited in the NCL Mutation Database, http://www.ucl.ac.uk/ncl/ ). Most
      mutations result in a classic morphology and disease phenotype, but some
      mutations are associated with disease that is of later onset, less severe or
      protracted in its course, or with atypical morphology. Seven common mutations
      exist, some having a worldwide distribution and others associated with families
      originating from specific geographical regions. This review attempts to correlate
      the gene, disease-causing mutation, morphology and clinical phenotype for each
      type of NCL.

PMID- 15965711
TI  - Immunological ignorance of solid tumors.
AB  - Many peripheral solid tumors such as sarcomas and carcinomas express tumor
      specific antigens that can serve as targets for immune effector T cells.
      Nevertheless, the immune surveillance against clinically manifest carcinomas and
      sarcomas seems relatively inefficient. Naive cytotoxic T cells are activated
      exclusively in secondary lymphoid organs including the spleen and lymph nodes.
      Tumor antigen might be either cross-presented to naive cytotoxic T cells by
      professional antigen-presenting cells (pAPC), or presented directly by tumor
      cells that migrated to secondary lymphoid organs. Direct priming is quite
      inefficient during early tumor development because metastasis to lymphoid organs
      is usually limited to advanced stage diseases. Similarly, the process of cross
      priming by pAPC seems to depend on relatively large antigen amounts and on
      maturation stimuli for dendritic cells, and both requirements may be limiting
      during initial tumorigenesis. Therefore, the immunosurveillance of solid tumors
      may fail because they are ignored for too long by the immune system. However,
      these situations may prove promising for the induction of tumor-specific T cell
      immunity by vaccination, as the T cell repertoire against these antigens has a
      naive phenotype and is not yet affected by tolerance mechanisms.

PMID- 15965712
TI  - CD4 T cells in tumor immunity.
AB  - T cell immunity is the key to protective immune responses against tumors.
      Traditionally, this function has been ascribed to CD8 T lymphocytes with
      cytotoxic activity, which are restricted by MHC class I molecules. In recent
      years the realization that CD4 T cells can also play a relevant role in
      protective anti-tumor responses has received growing attention. Here we will
      discuss the role of MHC class II-restricted T cells in response to, and in the
      regulation of, tumor antigens. Emphasis will be placed on four areas: (1) the
      role of CD4 T cell immunity in tumor protection in animal models and putative
      mode of action, (2) tumor antigens recognized by human CD4 T cells, (3) the
      cooperation between two CD4 T cells of different specificity as a new way to jump
      start the response against sub-immunogenic determinants of tumor antigens in a
      tolerant environment, and (4) the negative impact of regulatory CD4 T cells on
      anti-tumor T cell responses. By drawing attention to these four areas, it is our
      intention to provide the reader with a comprehensive view of issues of
      contemporary importance for this field, in the expectation that the information
      will help a better design of therapeutic cancer vaccines.

PMID- 15965714
TI  - Hyperthermophilic alpha-L: -arabinofuranosidase from Thermotoga maritima MSB8:
      molecular cloning, gene expression, and characterization of the recombinant
      protein.
AB  - A putative alpha-L: -arabinofuranosidase (AFase) gene belonging to family 51 of
      glycosyl hydrolases of a hyperthermophilic bacterium Thermotoga maritima MSB8 was
      cloned, sequenced, and overexpressed in Escherichia coli. The recombinant protein
      (Tm-AFase) was purified to apparent homogeneity by heat treatment (80 degrees C,
      30 min), followed by hydrophobic interaction, anion-exchange, and gel permeation
      column chromatography. Tm-AFase had a molecular mass of 55,284 Da on matrix
      assisted laser desorption ionization time-of-flight mass spectrometry and
      approximately 332 kDa on gel permeation column chromatography. Therefore, Tm
      AFase comprised six identical subunits as in the case of homologous AFase from
      Geobacillus stearothermophilus. Regarding substrate specificity, Tm-AFase was
      active with p-nitrophenyl alpha-L: -arabinofuranoside but not with p-nitrophenyl
      alpha-L: -arabinopyranoside. Regarding polysaccharides, Tm-AFase hydrolyzed
      arabinan and debranched arabinan but not arabinoxylan, arabinogalactan, and
      carboxymethyl cellulose. Tm-AFase was extremely thermophilic, displaying an
      optimal reaction temperature of 90 degrees C in a 10 min assay. When Tm-AFase was
      heated at 90 degrees C, no loss of activity was observed for at least 24 h. At
      100 degrees C, the activity dropped to approximately 50% in 20 min; thereafter,
      inactivation occurred very slowly exhibiting a half-life of approximately 2.7 h,
      characterizing the enzyme to be the most thermophilic AFase reported thus far.

PMID- 15965713
TI  - Effect of LLLT Ga-Al-As (685 nm) on LPS-induced inflammation of the airway and
      lung in the rat.
AB  - The purpose of this study was to investigate the effect of low level laser
      therapy (LLLT) on male Wistar rat trachea hyperreactivity (RTHR), bronchoalveolar
      lavage (BAL) and lung neutrophils influx after Gram-negative bacterial
      lipopolyssacharide (LPS) intravenous injection. The RTHR, BAL and lung
      neutrophils influx were measured over different intervals of time (90 min, 6 h,
      24 h and 48 h). The energy density (ED) that produced an anti-inflammatory effect
      was 2.5 J/cm(2), reducing the maximal contractile response and the sensibility of
      trachea rings to methacholine after LPS. The same ED produced an anti
      inflammatory effect on BAL and lung neutrophils influx. The Celecoxib COX-2
      inhibitor reduced RTHR and the number of cells in BAL and lung neutrophils influx
      of rats treated with LPS. Celecoxib and LLLT reduced the PGE(2) and TXA(2) levels
      in the BAL of LPS-treated rats. Our results demonstrate that LLLT produced anti
      inflammatory effects on RTHR, BAL and lung neutrophils influx in association with
      inhibition of COX-2-derived metabolites.

PMID- 15965715
TI  - Thermosediminibacter oceani gen. nov., sp. nov. and Thermosediminibacter
      litoriperuensis sp. nov., new anaerobic thermophilic bacteria isolated from Peru
      Margin.
AB  - A new group of anaerobic thermophilic bacteria was isolated from enrichment
      cultures obtained from deep sea sediments of Peru Margin collected during Leg 201
      of the Ocean Drilling Program. A total of ten isolates were obtained from cores
      of 1-2 m below seafloor (mbsf) incubated at 60 degrees C: three isolates came
      from the sediment 426 m below sea level with a surface temperature of 9 degrees C
      (Site 1227), one from 252 m below sea level with a temperature of 12 degrees C
      (Site 1228), and six isolates under sulfate-reducing condition from the lower
      slope of the Peru Trench (Site 1230). Strain JW/IW-1228P from the Site 1228 and
      strain JW/YJL-1230-7/2 from the Site 1230 were chosen as representatives of the
      two identified clades. Based on the 16S rDNA sequence analysis, these isolates
      represent a novel group with Thermovenabulum and Caldanaerobacter as their
      closest relatives. The temperature range for growth was 52-76 degrees C with an
      optimum at around 68 degrees C for JW/IW-1228P and 43-76 degrees C with an
      optimum at around 64 degrees C for JW/YJL-1230-7/2. The pH(25C) range for growth
      was from 6.3 to 9.3 with an optimum at 7.5 for JW/IW-1228P and from 5 to 9.5 with
      an optimum at 7.9-8.4 for JW/YJL-1230-7/2. The salinity range for growth was from
      0% to 6% (w/v) for JW/IW-1228P and from 0% to 4.5% (w/v) for JW/YJL-1230-7/2. The
      G+C [corrected] mol% of the genomic DNA was 46.3 +/- 0.7% (n = 4) for
      Thermosediminibacter oceani [corrected] JW/IW-1228PT [corrected] and 45.2 +/- 0.7
      (n = 6) for Thermosediminibacter litoriperuensis [corrected] JW/YJL-1230-7/2T
      [corrected] DNA-DNA hybridization yielded 52% similarity between the two strains.
      According to 16S rRNA gene sequence analysis, the isolates are located within the
      family, Thermoanaerobacteriaceae. Based on their morphological and physiological
      properties and phylogenetic analysis, it is proposed that strain JW/IW-1228P(T)
      is placed into a novel taxa, Thermosediminibacter oceani, gen. nov., sp. nov.
      (DSM 16646(T)=ATCC BAA-1034(T)), and JW/YJL-1230-7/2(T) into Thermosediminibacter
      litoriperuensis sp. nov. (DSM 16647(T) =ATCC BAA-1035(T)).

PMID- 15965717
TI  - Genetic diversity in Microcystis populations of a French storage reservoir
      assessed by sequencing of the 16S-23S rRNA intergenic spacer.
AB  - We compared the genetic diversity of the 16S-23S spacer of the rRNA gene (ITS1)
      in benthic and pelagic colonies of the Microcystis genus isolated from two
      different sampling stations with different depths and at two different sampling
      times (winter and summer) in the French storage reservoir of Grangent. In all, 66
      ITS1 sequences were found in the different clone libraries. The nucleotide
      diversity of all the sampled isolates were in the same range (average number =
      0.022) regardless of their origin, showing that several clones are involved in
      the summer bloom event and contribute to the high biomass production.
      Phylogenetic study and analysis of molecular variance (AMOVA) revealed no obvious
      genetic differentiation between the benthic and pelagic isolates. This finding
      confirms that the Microcystis genus in this lake is characterized by having both
      a benthic phase in winter and spring allowing this organism to survive in
      unfavorable environmental conditions, and a pelagic phase in summer and autumn
      when environmental conditions allow them to grow in the water column. Finally,
      comparing these sequences with those available in the GenBank database showed
      that some highly conserved genotypes are found throughout the world.

PMID- 15965718
TI  - Dissolved oxygen saturation controls PAH biodegradation in freshwater estuary
      sediments.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in terrestrial
      and aquatic environments and can represent a significant constituent of the
      carbon pool in coastal sediments. We report here the results of an 18-month
      seasonal study of PAH biodegradation and heterotrophic bacterial production and
      their controlling biogeochemical factors from 186 sediment samples taken in a
      tidally influenced freshwater estuary. For each sampling event, measurements were
      averaged from 25-45 stations covering approximately 250 km(2). There was a clear
      relationship between bacterial production and ambient temperature, but none
      between production and bottom water dissolved oxygen (DO) % saturation or PAH
      concentrations. In contrast with other studies, we found no effect of temperature
      on the biodegradation of naphthalene, phenanthrene, or fluoranthene. PAH
      mineralization correlated with bottom water DO saturation above 70% (r(2) >
      0.99). These results suggest that the proportional utilization of PAH carbon to
      natural organic carbon is as much as three orders of magnitude higher during
      cooler months, when water temperatures are lower and DO % saturation is higher.
      Infusion of cooler, well-oxygenated water to the water column overlying
      contaminated sediments during the summer months may stimulate PAH metabolism
      preferentially over non-PAH organic matter.

PMID- 15965719
TI  - Aerobic organic carbon mineralization by sulfate-reducing bacteria in the oxygen
      saturated photic zone of a hypersaline microbial mat.
AB  - The sulfate-reducing bacterium strain SRB D2 isolated from the photic zone of a
      hypersaline microbial mat, from Lake Chiprana, NE Spain, respired pyruvate,
      alanine, and alpha-ketoglutarate but not formate, lactate, malate, succinate, and
      serine at significant rates under fully oxic conditions. Dehydrogenase enzymes of
      only the former substrates are likely oxygen-tolerant as all substrates supported
      anaerobic sulfate reduction. No indications were found, however, that aerobic
      respiration supported growth. Although strain SRB D2 appeared phylogenetically
      closely related to the oxygen-tolerant sulfate-reducing bacterium Desulfovibrio
      oxyclinae, substrate spectra were markedly different. Most-probable-number (MPN)
      estimates of sulfate-reducing bacteria and aerobic heterotrophic bacteria
      indicated that the latter were numerically dominant in both the photic and
      aphotic zones of the mat. Moreover, substrate spectra of representative isolates
      showed that the aerobic heterotrophic bacteria are metabolically more diverse.
      These findings indicate that sulfate-reducing bacteria in the fully oxic photic
      zone of mats have to compete with aerobic heterotrophic bacteria for organic
      substrates. Porewater analysis revealed that total carbohydrates and low
      molecular-weight carbon compounds (LMWC) made up substantial fractions of the
      total dissolved organic carbon (DOC) pool and that nighttime degradation of the
      former was concomitant with increased concentration of the latter. Our findings
      indicate that aerobic respiration by sulfate-reducing bacteria contributes to
      organic carbon mineralization in the oxic zone of microbial mats as daytime
      porewater LMWC concentrations are above typical half-saturation constants.

PMID- 15965720
TI  - Nutrient and temperature limitation of bacterioplankton growth in temperate
      lakes.
AB  - Limitation of bacterioplankton production by nutrients and temperature was
      investigated in eight temperate lakes in summer. Six of the lakes were resampled
      in autumn. The lakes differ in nutrient content, water color, and concentration
      of dissolved organic carbon. Nutrients (phosphorus, nitrogen, and organic carbon)
      were added alone and in all possible combinations to filtered lake water
      inoculated with bacteria from the lake. After incubation for 36-40 h at in situ
      temperatures (ranging from 7 to 20 degrees C), the response in bacterioplankton
      production was determined. The effect of increased temperature on
      bacterioplankton growth was also tested. Bacterioplankton production was often
      limited by phosphorus alone, organic carbon alone, or the two in combination.
      Phosphorus limitation of bacterioplankton production was more common in the
      summer, whereas limitation by organic carbon was more frequently observed in the
      autumn. There was a close balance between limitation by phosphorus and organic
      carbon in the epilimnion in the summer. In the hypolimnion in the summer,
      bacterioplankton growth was primarily phosphorus-limited. The effect of
      phosphorus additions decreased with increasing phosphorus concentrations in the
      lakes. However, there were no correlations between the effect of added organic
      carbon and water color, dissolved organic carbon concentration, or phosphorus
      concentration. When temperature was low (in the hypolimnion in the summer, and
      throughout the water column in the autumn) temperature also limited
      bacterioplankton production. Thus, temperature and inorganic nutrients or organic
      compounds can limit bacterioplankton growth both alone and simultaneously.
      However, at low temperatures, temperature is the most important factor
      influencing bacterioplankton growth.

PMID- 15965721
TI  - Isolation and characterization of Cryptococcus neoformans varieties recovered
      from natural sources in Bogota, Colombia, and study of ecological conditions in
      the area.
AB  - Cryptococcus neoformans, the etiological agent of cryptococcosis, has been
      associated with avian droppings and certain trees in different countries,
      including Colombia. C neoformans environmental isolates were obtained in urban
      areas in Bogota, Colombia, and the strains recovered were phenotypically
      characterized. Attempts to determine the ecological conditions (micro- and
      macroclimatic) possibly related to their habitat were also undertaken. Four
      hundred and eighty samples from bark, soil around trunk bases, and detritus
      inside hollows of 32 trees were collected in three urban areas during a 5-month
      period, as well as 89 avian droppings samples from different places. Of plant
      samples, 6.7% collected from nine tree species yielded C. neoformans var. gattii,
      serotype B strains in 99% of the cases, and C. neoformans var. grubii, serotype A
      in 1%. The yeast was more frequently recovered from bark than from soil or
      detritus inside hollows, and from trees with hollows or rotted wood rather than
      from trees in which birds nest. C. neoformans was present with higher frequency
      and density in the rainy season than in the dry season; we found that slightly
      higher temperature and humidity values of the microhabitat, as compared to those
      of the environment, favored fungal occurrence, but the phenological state of the
      tree did not. Of dropping samples, 7.9% yielded C. neoformans strains, all of
      them C. neoformans var. grubii, serotype A. The yeast was obtained more
      frequently from dry droppings than from moist ones, but neither the sunlight
      exposure nor the site of collection of samples was correlated with this
      occurrence. Population density was significantly higher in droppings than in tree
      samples. Under laboratory conditions, isolates of different serotype showed
      similar capsular sizes. Water content and pH ranges were wide and did not show
      any significant difference between positive and negative samples.

PMID- 15965722
TI  - Microbial food webs in boreal humic lakes and reservoirs: ciliates as a major
      factor related to the dynamics of the most active bacteria.
AB  - In order to assess the factors that determine the dynamics of bacteria with high
      nucleic acid content in aquatic systems, we (i) conducted 24-h in situ dialysis
      experiments, involving different fractions of plankton and unfiltered water and
      (ii) examined empirical relationships between bacteria and both abiotic factors
      and protists, in boreal humic freshwaters (reservoir and lakes) in the James Bay
      region (Quebec, Canada). Bacteria were subdivided into two subgroups on the basis
      of their nucleic acid content assessed by flow cytometry. The abundance of
      bacteria with the highest nucleic acid content and high light scatter (HNA-hs)
      was significantly correlated, across sites, to bacterial production, whereas
      bacteria with lower nucleic acid content (LNA) and total bacteria were not. In
      addition, HNA-hs growth was higher and more variable than LNA growth, indicating
      that HNA-hs were the most dynamic bacteria. Heterotrophic nanoflagellate and
      ciliate biomass represented, on average, 5 and 13% of bacterial biomass,
      respectively. Both in ambient waters and in experiments, ciliates were
      significantly and negatively correlated with bacteria, whereas heterotrophic
      nanoflagellates, likely under the grazing pressure from ciliates and
      metazooplankton, were not. Among ciliates, Cyclidium glaucoma appeared to play an
      important role. Its growth was significantly and negatively correlated to that of
      HNA-hs but not to that of LNA. In ambient waters, the abundance of this species
      explained 56% of the variations in HNA-hs abundance and only 27% of those for
      LNA. The abundances of total bacteria and LNA significantly increased with
      chlorophyll a, whereas those of HNA-hs did not. In addition, during the
      experiments, the estimated potential losses of HNA-hs significantly increased
      with the initial abundance of C. glaucoma. These results suggest selective
      removal of the most dynamic bacteria by C. glaucoma and indicate that ciliates
      may play an important role in the dynamics of active bacteria in natural waters.
      These findings suggest the existence, within the aquatic microbial food webs, of
      keystone species that are very important in regulating the activity structure of
      bacteria.

PMID- 15965723
TI  - Effects of microbial community diversity on the survival of Pseudomonas
      aeruginosa in the wheat rhizosphere.
AB  - Ecological theory suggests that microbial communities with greater microbial
      diversity would be less susceptible to invasion by potential opportunistic
      pathogens. We investigated whether the survival of the opportunistic pathogen
      Pseudomonas aeruginosa in the wheat rhizosphere would be affected by the presence
      of natural and constructed microbial communities of various diversity levels.
      Three levels of microbial community diversity were derived from wheat roots by a
      dilution/extinction approach. These wheat rhizosphere inocula, as well as a
      gnotobiotic microbial community consisting of seven culturable wheat
      rhizobacterial isolates, were introduced into the nutrient solution of
      hydroponically grown wheat plants on the day of planting. Phenotypic
      characterization of the culturable microbial communities on R2A medium, Shannon
      microbial diversity index, community-level physiological profiles, and terminal
      restriction fragment length polymorphisms were used to assess the varying
      microbial diversity levels. At day 7 the roots were invaded with P. aeruginosa
      and the number of P. aeruginosa colony forming units per root were measured at
      day 14. The average number of surviving P. aeruginosa cells was 3.52, 4.90, 7.18,
      6.65 log(10) cfu/root in the high, medium, low, and gnotobiotic microbial
      community diversity level treatments, respectively. The invasibility of the
      rhizosphere communities by P. aeruginosa was inversely related to the level of
      diversity from the dilution extinction gradient. The gnotobiotic community did
      not confer protection against P. aeruginosa invasion. Although these data
      indicate that invasibility is inversely related to diversity, further study is
      needed to both reproduce these findings and define the specific mechanisms of the
      diversity effect.

PMID- 15965724
TI  - Heterotrophic fixation of CO(2) in soil.
AB  - The occurrence of heterotrophic CO(2) fixation by soil microorganisms was tested
      in several mineral soils differing in pH and two artificial soils (a mixture of
      silica sand, alfalfa powder, and nutrient medium inoculated with a soil
      suspension). Soils were incubated at ambient ( approximately 0.05 vol%) and
      elevated ( approximately 5 vol%) CO(2) concentrations under aerobic conditions
      for up to 21 days. CO(2) fixation was detected using either a technique for
      determining the natural abundance of (13)C or by measuring the distribution of
      labeled (14)C-CO(2) in soil and bacteria. The effects of elevated CO(2) on
      microbial biomass (direct counts, chloroform fumigation extraction method),
      composition of microbial community (phospholipid fatty acids), microbial activity
      (respiration, dehydrogenase activity), and turnover rate were also measured.
      Heterotrophic CO(2) fixation was proven in all soils under study, being higher in
      neutral soils. The main portion of the fixed CO(2) (98-99%) was found in
      extracellular metabolites while only approximately 1% CO(2) was incorporated into
      microbial cells. High CO(2) concentration always induced an increase in microbial
      activity, changes in the composition of the microbial community, and a decrease
      in microbial turnover. The results suggest that heterotrophic CO(2) fixation
      could be a widespread process in soils.

PMID- 15965725
TI  - Rickettsia infection in natural leech populations.
AB  - Field-collected specimens of glossiphoniid leeches, Torix tagoi, Torix tukubana,
      Hemiclepsis marginata, and Hemiclepsis japonica, were surveyed for Rickettsia
      infection by using a diagnostic PCR assay. Rickettsia was detected in 96% (69/72)
      of T. tagoi, 83% (24/29) of T. tukubana, 29% (33/113) of H. marginata, and 0%
      (0/30) of H. japonica. The frequencies of Rickettsia infection were stably
      maintained in different seasons. In H. marginata and T. tukubana, distant local
      populations exhibited remarkably different frequencies of Rickettsia infection.
      Eggs carried by infected females of T. tagoi and H. marginata were all Rickettsia
      positive, indicating nearly 100% vertical transmission. Analysis of 16S rDNA
      sequences revealed that phylogenetic relationship of the leech-associated
      Rickettsia reflected the specific and populational divisions of the host leeches.
      However, circumstantial lines of evidence strongly suggested that horizontal
      transmission of Rickettsia must have occurred in the ancestors of these leeches.
      In T. tagoi and T. tukubana, infected individuals were remarkably larger in size
      than uninfected individuals, wheras in H. marginata, infected and uninfected
      individuals were almost comparable in size. This study first provides information
      on ecological aspects of leech-bone endocellular bacteria of the genus
      Rickettsia. On the basis of these data, we discuss possible mechanisms whereby
      Rickettsia infection is maintained in natural populations of these leeches in the
      freshwater ecosystem.

PMID- 15965726
TI  - Using phospholipid fatty acid technique to study short-term effects of the
      biological control agent Pseudomonas fluorescens DR54 on the microbial microbiota
      in barley rhizosphere.
AB  - The biological control agent (BCA) Pseudomonas fluorescens DR54 was applied to
      seeds (experiment 1) or roots (experiment 2) of barley growing in microcosms,
      while noninoculated plants served as controls. The fate of the BCA and its
      effects on the rhizosphere microbial community was evaluated in microcosms
      destructively sampled at days 2, 4, 6, and 9 after inoculation. In both
      experiments the number of P. fluorescens DR54 cells decreased immediately after
      application as enumerated by immunostaining and microscope direct counting.
      Substrate-induced respiration (SIR) was taken as a measurement of the active
      microbial biomass, while indicators of the total microbiota (and main taxonomic
      groups) were obtained using the phospholipid fatty acid (PLFA) technique. In
      experiment 1, these parameters were unaffected by the relatively small number of
      BCA cells applied, whereas in experiment 2, the larger BCA input resulted in an
      enhanced level of both SIR and PLFAs from Gram-negative bacteria (which included
      the BCA itself). However, at day 9 after inoculation, treatments with P.
      fluorescens DR54 and controls were similar in all measured parameters in both
      experiments. This was also illustrated very clearly by principal component
      analysis of the PLFA data, which in both experiments were able to discriminate
      between treatments in the first days after BCA inoculation, thus confirming the
      sensitivity of this method. Laccase activity has a potential as an indicator of
      fungal stress, e.g., when challenged with an antifungal BCA. This seemed to be
      supported in experiment 2, where the activity of this enzyme was enhanced four
      fold in the BCA treatment at day 2. Our study shows that under the present
      conditions, P. fluorescens DR54 disappears from the soil and causes only
      transient effects on the soil microbiota. It also shows that the PLFA technique
      is a sensitive and reliable monitoring tool in in situ assessment of BCA
      nontarget effect on indigenous microorganisms in soil.

PMID- 15965727
TI  - Methanogen communities in a drained bog: effect of ash fertilization.
AB  - Forestry practises such has drainage have been shown to decrease emissions of the
      greenhouse gas methane (CH(4)) from peatlands. The aim of the study was to
      examine the methanogen populations in a drained bog in northern Finland, and to
      assess the possible effect of ash fertilization on potential methane production
      and methanogen communities. Peat samples were collected from control and ash
      fertilized (15,000 kg/ha) plots 5 years after ash application, and potential
      CH(4) production was measured. The methanogen community structure was studied by
      DNA isolation, PCR amplification of the methyl coenzyme-M reductase (mcr) gene,
      denaturing gradient gel electrophoresis (DGGE), and restriction fragment length
      polymorphism (RFLP) analysis. The drained peatland showed low potential methane
      production and methanogen diversity in both control and ash-fertilized plots.
      Samples from both upper and deeper layers of peat were dominated by three groups
      of sequences related to Rice cluster-I hydrogenotroph methanogens. Even though pH
      was marginally greater in the ash-treated site, the occurrence of those sequences
      was not affected by ash fertilization. Interestingly, a less common group of
      sequences, related to the Fen cluster, were found only in the fertilized plots.
      The study confirmed the depth related change of methanogen populations in
      peatland.

PMID- 15965728
TI  - Bacterial choices for the consumption of multiple resources for current and
      future needs.
AB  - Microorganisms differ in their effectiveness in uptake and selection of
      substances that they bring in from the environment. They also differ in how they
      balance the allocation of nutrients for immediate and for delayed use. Moreover,
      they may not take up resources as fast as they seemingly could, and they may
      extrude derivatives of substances just pumped in. A good deal of these apparent
      choices must reside in the uptake systems and the linkage of these with the
      cell's intermediate metabolism. An important feature is that a resource may vary
      in concentration from time to time, nutrient to nutrient, and habitat to habitat.
      This variation must have been critical to the evolution of regulatory processes.
      Some possibilities for the combined uptake and consumption are considered for
      substrates serving the same (homologous) and different (heterologous) roles for
      the bacterium. From the membrane transport processes diagrammed in Fig. 1c and
      Fig. 2 and corresponding computer program given in Appendix A, the combined
      effect of uptake processes and cell growth can be studied. The model can be
      modified for various alternate models to study the possible control of cellular
      uptake and metabolism for the range of ecological roles of the bacterium.

PMID- 15965729
TI  - In-transit recurrence after sentinel lymph node biopsy in melanoma: primum non
      nocere.

PMID- 15965730
TI  - Surgical resection of primary tumors in patients who present with stage IV
      colorectal cancer: an analysis of surveillance, epidemiology, and end results
      data, 1988 to 2000.
AB  - BACKGROUND: Surgical resection of the primary tumor for patients who present with
      incurable stage IV colorectal cancer is controversial. National practice patterns
      have not been described. We evaluated the use of primary tumor resection in
      patients presenting with stage IV colorectal cancer. METHODS: Patients with stage
      IV colorectal cancer diagnosed between 1988 and 2000 were selected from the
      Surveillance, Epidemiology, and End Results database. Patients undergoing primary
      tumor resection were analyzed on the basis of sex, race, year of diagnosis, and
      the anatomical site of the primary tumor. We compared the survival of resected
      and nonresected patients. RESULTS: A total of 17,658 (66%) of the 26,754 patients
      presenting with stage IV colorectal cancer underwent primary tumor resection.
      Patients with resected disease were more likely to be young (mean age of 67.1 vs.
      70.3 years) and to have right-sided tumors (75.3%, 73.0%, and 45.6%,
      respectively, for right, left, and rectal; P < .001). In all age groups, patients
      undergoing resection had higher median and 1-year survival rates (colon: 11 vs. 2
      months, 45% vs. 12%, P < .001; rectum: 16 vs. 6 months, 59% vs. 25%, P < .001)
      when compared with patients who did not undergo resection. CONCLUSIONS: Most
      patients who present with stage IV colorectal cancer undergo resection of the
      primary tumor. The proportion of patients undergoing resection depends on patient
      age and race and the anatomical location of the primary tumor. The degree to
      which case selection explains the treatment and survival differences observed is
      not known. Further investigation of the role of surgery in the management of
      incurable stage IV colorectal cancer is warranted.

PMID- 15965731
TI  - Significant long-term survival after radiofrequency ablation of unresectable
      hepatocellular carcinoma in patients with cirrhosis.
AB  - BACKGROUND: Radiofrequency ablation (RFA) offers an alternative treatment in some
      unresectable hepatocellular carcinoma (HCC) patients with disease confined to the
      liver. We prospectively evaluated survival rates in patients with early-stage,
      unresectable HCC treated with RFA. METHODS: All patients with HCC treated with
      RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated.
      Patients were treated with RFA by using a percutaneous or open intraoperative
      approach with ultrasound guidance and were evaluated at regular intervals to
      determine disease recurrence and survival. RESULTS: A total of 194 patients (153
      men [79%] and 41 women [21%]) with a median age of 66 years (range, 39-86 years)
      underwent RFA of 289 sonographically detectable HCC tumors. All patients were
      followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous
      and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients,
      respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease
      recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated
      percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local
      recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic.
      The overall complication rate was 12%. Overall survival rates at 1, 3, and 5
      years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively.
      CONCLUSIONS: Treatment with RFA can produce significant long-term survival rates
      for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed
      in these patients with relatively low complication rates. Confirmation of these
      results in randomized trials should be considered.

PMID- 15965732
TI  - Preoperative chemoradiotherapy (modified Eilber protocol) provides maximum local
      control and minimal morbidity in patients with soft tissue sarcoma.
AB  - BACKGROUND: Local recurrence rates of 15% to 30% after treatment of soft tissue
      sarcoma (STS) are still common but unacceptable. Our hypothesis was that a
      refined neoadjuvant chemotherapy and radiation protocol (modified Eilber
      protocol) improves local control rates while minimizing major morbidity. METHODS:
      Consecutive patients with STS deep to the fascia of the extremity or trunk during
      1984 to 1996 were treated with 3 days of doxorubicin (30 mg/day) and sequential
      radiation (300 cGy/day for 10 days). Wide excision with limb preservation was
      performed 4 to 8 weeks after radiation completion. Treatment complications,
      margins, local recurrence, and survival were prospectively documented. RESULTS:
      Of 75 patients, 66% had tumors >5 cm, and 71% were grade 2/3. In eight patients,
      negative margins were not achieved, and four of these had amputation (95% limb
      salvage). Three of the remaining four had local recurrence with a 5- and 7-year
      actuarial local control rate of 50% and 25%, respectively. In contrast, of the 67
      patients with negative margins, a local control rate of 97% at 5 years and 94% at
      7 years and an overall survival of 63% were achieved. Although margin (P = .001)
      and stage (P = .035) were correlated, these were not significant on multivariate
      Cox regression analysis. Risk factors for death included tumor stage (hazard
      ratio, 1.54; P = .001) and tumor grade (hazard ratio, 1.4; P = .02). Three
      patients (4%) required reoperation for tissue loss, and eight patients (10.6%)
      developed minor wound complications. CONCLUSIONS: This modified Eilber protocol
      seems to maximize local control and minimize major wound complications for
      extremity/truncal STS.

PMID- 15965733
TI  - A test of enhancing model accuracy in high-throughput crystallography.
AB  - The high throughput of structure determination pipelines relies on increased
      automation and, consequently, a reduction of time spent on interactive quality
      control. In order to meet and exceed current standards in model accuracy, new
      approaches are needed for the facile identification and correction of model
      errors during refinement. One such approach is provided by the validation and
      structure-improvement tools of the MOL: PROBITY: web service. To test their
      effectiveness in high-throughput mode, a large subset of the crystal structures
      from the SouthEast Collaboratory for Structural Genomics (SECSG) has used
      protocols based on the MOL: PROBITY: tools. Comparison of 29 working-set and 19
      control-set SECSG structures shows that working-set outlier scores for updated
      Ramachandran-plot, sidechain rotamer, and all-atom steric criteria have been
      improved by factors of 5- to 10-fold (relative to the control set or to a Protein
      Data Bank sample), while quality of covalent geometry, R(work), R(free), electron
      density and difference density are maintained or improved. Some parts of this
      correction process are already fully automated; other parts involve manual
      rebuilding of conformations flagged by the tests as trapped in the wrong local
      minimum, often altering features of functional significance. The ease and
      effectiveness of this technique shows that macromolecular crystal structures from
      either traditional or high-throughput determinations can feasibly reach a new
      level of excellence in conformational accuracy and reliability.

PMID- 15965734
TI  - Pilot studies on the parallel production of soluble mouse proteins in a bacterial
      expression system.
AB  - We investigated the parallel production in medium throughput of mouse proteins,
      using protocols that involved recombinatorial cloning, protein expression
      screening and batch purification. The methods were scaled up to allow the
      simultaneous processing of tens or hundreds of protein samples. Scale-up was
      achieved in two stages. In an initial study, 30 targets were processed manually
      but with common protocols for all targets. In the second study, these protocols
      were applied to 96 target proteins that were processed in an automated manner.
      The success rates at each stage of the study were similar for both the manual and
      automated approaches. Overall, 15 of the selected 126 target mouse genes (12%)
      yielded soluble protein products in a bacterial expression system. This success
      rate compares favourably with other protein screening projects, particularly for
      eukaryotic proteins, and could be further improved by modifications at the
      cloning step.

PMID- 15965735
TI  - Structure-based functional identification of a novel heme-binding protein from
      Thermus thermophilus HB8.
AB  - The TT1485 gene from Thermus thermophilus HB8 encodes a hypothetical protein of
      unknown function with about 20 sequence homologs of bacterial or archaeal origin.
      Together they form a family of uncharacterized proteins, the cluster of
      orthologous group COG3253. Using a combination of amino acid sequence analysis,
      three-dimensional structural studies and biochemical assays, we identified TT1485
      as a novel heme-binding protein. The crystal structure reveals that this protein
      is a pentamer and each monomer exhibits a beta-barrel fold. TT1485 is
      structurally similar to muconolactone isomerase, but this provided no functional
      clues. Amino acid sequence analysis revealed remote homology to a heme enzyme,
      chlorite dismutase. Strikingly, amino acid residues that are highly conserved in
      the homologous hypothetical proteins and chlorite dismutase cluster around a deep
      cavity on the surface of each monomer. Molecular modeling shows that the cavity
      can accommodate a heme group with a strictly conserved His as a heme ligand.
      TT1485 reconstituted with iron protoporphyrin IX chloride gave a low chlorite
      dismutase activity, indicating that TT1485 catalyzes a reaction other than
      chlorite degradation. The presence of a possible Fe-His-Asp triad in the heme
      proximal site suggests that TT1485 functions as a novel heme peroxidase to
      detoxify hydrogen peroxide within the cell.

PMID- 15965736
TI  - NMR solution structure of Thermotoga maritima protein TM1509 reveals a Zn
      metalloprotease-like tertiary structure.
AB  - The 150-residue protein TM1509 is encoded in gene YF09_THEMA of Thermotoga
      maritima. TM1509 has so far no functional annotation and belongs to protein
      family UPF0054 (PFAM accession number: PF02130) which contains at least 146
      members. The NMR structure of TM1509 reveals an alpha+beta fold comprising a four
      stranded beta-sheet with topology A( upward arrow), B( upward arrow), D( upward
      arrow), C( downward arrow) as well as five alpha-helices I-V. The structures of
      most members of family PF02130 can be reliably constructed using the TM1509 NMR
      structure, demonstrating high leverage for exploration of fold space. A multiple
      sequence alignment of TM1509 with homologues of family UPF0054 shows that three
      polypeptide segments, as well as a putative zinc-binding consensus motif
      HGXLHLXGYDH located at the C-terminal end of alpha-helix IV, are highly
      conserved. The spatial arrangement of the three His residues of this UPF0054
      consensus motif is similar to the arrangement found for the His residues in the
      HEXXHXXGXXH zinc-binding consensus motif of matrix metallo-proteases (MMPs).
      Moreover, the other conserved polypeptide segments form a large cavity which
      encloses the putative Zn-binding pocket and might confer specificity during
      catalysis. However, TM1509 and the other members of the UPF0054 family do not
      have the crucial Glu residue in position 2 of the MMP consensus motif.
      Intriguingly, the TM1509 structure indicates that the Asp in the UPF0054
      consensus motif (Asp 111 in TM1509) may overtake the catalytic role of the Glu.
      This suggests that protein family UPF0054 might contain members of a hitherto
      uncharacterized class of metalloproteases.

PMID- 15965737
TI  - Acrylic scaffolds with interconnected spherical pores and controlled
      hydrophilicity for tissue engineering.
AB  - Polymer scaffolds are obtained in which the geometric characteristics (pore size,
      connectivity, porosity) and the physico-chemical properties of the resulting
      material can be controlled in an independent way. The interconnected porous
      structure was obtained using a template of sintered PMMA microspheres of
      controlled size. Copolymerization of hydrophobic ethyl acrylate and hydrophilic
      hydroxyethyl methacrylate comonomers took place in the free space of the
      template, different comonomer ratio gave rise to different hydrophilicity degrees
      of the material keeping the same pore architecture. The morphology of the
      resulting scaffolds was investigated by scanning electron microscopy (SEM), the
      porosity of the material calculated, and the mechanical properties compared with
      those of the bulk (non porous) material of the same composition.

PMID- 15965738
TI  - Synthesis, characterization and melt spinning of a block copolymer of L-lactide
      and epsilon-caprolactone for potential use as an absorbable monofilament surgical
      suture.
AB  - This paper describes the synthesis and characterization of a block copolymer of L
      lactide (LL) and epsilon -caprolactone (CL) and its subsequent melt spinning into
      a monofilament fiber. The synthesis reaction was a two-step process. In the first
      step, an approximately 50:50 mol% random copolymer, P(LL-co-CL), was synthesized
      via bulk copolymerization of LL and CL. This first-step prepolymer then became
      the macroinitiator in the second-step reaction in which more LL monomer was added
      to form a block copolymer, PLL-b-P(LL-co-CL)-b-PLL. Both the prepolymer and block
      copolymer were characterized by a combination of analytical techniques comprising
      dilute-solution viscometry, GPC, 1H and 13C NMR, DSC and TG. The block copolymer
      was then processed into a monofilament fiber using a small-scale melt spinning
      apparatus. The fiber was spun with a minimum amount of chain orientation and
      crystallinity so that its semi-crystalline morphology could be constructed under
      more controlled conditions in subsequent off-line hot-drawing and annealing
      steps. In this way, the fiber's tensile properties and dimensional stability were
      developed, as indicated by the changes in its stress-strain curve. The final
      drawn and annealed fiber had a tensile strength (>400 MPa) approaching that of a
      commercial PDS II suture of similar size. It is considered that this type of
      block copolymer has the potential to be developed further as a lower-cost
      alternative to the current commercial monofilament surgical sutures.

PMID- 15965739
TI  - Carbonate-containing hydroxyapatite derived from calcium tripolyphosphate gel
      with urea.
AB  - Carbonate containing hydroxyapatite (CO3HAp) is one of the candidate materials as
      a bioresorbable bone substitute. In the present work, CO3HAp was efficiently
      prepared by a hydrothermal treatment of calcium tripolyphosphate gel with urea at
      140 degrees C for 24 h. Chemical potential plots of the CO3HAp for estimation of
      its dissolution behavior suggested that the CO3HAp is more soluble than
      hydroxyapatite (HAp) and is as soluble as octacalcium phosphate (OCP) and/or beta
      -tricalcium phosphate (TCP). This material is expected to be applied to
      bioresorbable materials such as bone fillers.

PMID- 15965740
TI  - Synthesis of bioactive PMMA bone cement via modification with
      methacryloxypropyltri-methoxysilane and calcium acetate.
AB  - Bone cement consisting of polymethylmethacrylate (PMMA) powder and
      methylmethacrylate (MMA) liquid is clinically used for fixation of implants such
      as artificial hip joints. However, it does not show bone-bonding ability, i.e.,
      bioactivity. The lack of bioactivity would be one of factors which cause
      loosening between the cement and the implant. The present authors recently showed
      the potential of bioactive PMMA-based bone cement through modification with gamma
      methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the
      effects of the kinds of PMMA powder on setting time, apatite formation and
      compressive strength were investigated in a simulated body fluid (Kokubo
      solution). The cement modified with calcium acetate calcined at 220 degrees C
      could set within 15 min when the PMMA powder had an average molecular weight of
      100,000 or less. The addition of calcium acetate calcined at 120 degrees C in the
      PMMA powder required a much longer period for setting. The modified cements
      formed an apatite layer after soaking in the Kokubo solution within 1 day for
      cement starting from PMMA powder with a molecular weight of 100,000 or less.
      Compressive strengths of the modified cements were more than 70 MPa for cements
      starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo
      solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in
      molecular weight showed a smaller decrease in compressive strength than that
      consisting of 56,000 in molecular weight. These results indicate that bioactive
      PMMA cement can be produced with appropriate setting time and mechanical strength
      when PMMA powders with a suitable molecular weight are used. Such a type of
      design of bioactive PMMA bone cement leads to a novel development of bioactive
      material for bone substitutes.

PMID- 15965741
TI  - Osteoblast cell adhesion on a laser modified zirconia based bioceramic.
AB  - Due to their attractive mechanical properties, bioinert zirconia bioceramics are
      frequently used in the high load-bearing sites such as orthopaedic and dental
      implants, but they are chemically inert and do not naturally form a direct bond
      with bone and thus do not provide osseointegration. A CO2 laser was used to
      modify the surface properties with the aim to achieve osseointegration between
      bioinert zirconia and bone. The surface characterisation revealed that the
      surface roughness decreased and solidified microstructure occurred after laser
      treatment. Higher wettability characteristics generated by the CO2 laser
      treatment was primarily due to the enhancement of the surface energy,
      particularly the polar component, determined by microstructural changes. An in
      vitro test using human fetal osteoblast cells (hFOB) revealed that osteoblast
      cells adhere better on the laser treated sample than the untreated sample. The
      change in the wettability characteristics could be the main mechanism governing
      the osteoblast cell adhesion on the YPSZ.

PMID- 15965742
TI  - Shear bond strength of adhesive systems to enamel and dentin. Thermocycling
      influence.
AB  - OBJECTIVES: The purpose of the this study was to evaluate the influence of
      thermocycling on shear bond strength on bovine enamel and dentin surfaces of
      different adhesive systems. METHODS: Thirty sound bovine incisors were sectioned
      in mesiodistal and inciso-cervical direction obtaining 60 incisal surfaces
      (enamel) and 60 cervical surfaces (dentin). Specimens were randomly assigned to 3
      groups of equal size (n=40), according to the adhesive system used: I-Single
      Bond; II-Prime & Bond NT/NRC; III-One Coat Bond. After 24-h storage in distilled
      water at 37 degrees C, each main group was divided into two subgroups: A
      specimens tested after 24 h storage in distilled water at 37 degrees C; B
      specimens submitted to thermocycling (500 cycles). Shear bond strength tests were
      performed. Data were submitted to ANOVA and Tukey test. RESULTS: Means (MPa) of
      different groups were: I-AE-16.96, AD-17.46; BE-21.60, BD-12.79; II-AE-17.20, AD
      11.93; BE-20.67, BD-13.94; III-AE-25.66, AD-17.53; BE-24.20, BD-19.38.
      SIGNIFICANCE: Thermocycling did not influence significantly the shear bond
      strength of the tested adhesive systems; enamel was the dental substrate that
      showed larger adhesive strength; One Coat Bond system showed the best adhesive
      strength averages regardless of substrate or thermocycling.

PMID- 15965743
TI  - The crystallization of Hydroxyapatite in the presence of sodium alginate.
AB  - The effect of sodium alginate on the crystal growth of hydroxyapatite (HAP) was
      investigated at sustained supersaturation by the constant composition technique.
      Sodium alginate was found to inhibit HAP crystal growth at low concentrations and
      reduced the crystal growth rates by 42-86% for inhibitor concentrations of
      2.1x10(-7)-12.6x10(-7) mol/l. The inhibition effect on the crystal growth rate
      may be explained possibly through adsorption onto the active growth sites. A
      detailed kinetics analysis suggested a Langmuir-type adsorption of the alginate
      on HAP surface and a value of 1.63x10(7) l/mol was obtained for the affinity
      constant of sodium alginate for the surface of HAP. The apparent order for the
      crystallization reaction was determined to be approximately 2, thus suggesting a
      surface diffusion controlled spiral growth mechanism.

PMID- 15965744
TI  - Macroporous calcium phosphate glass-ceramic prepared by two-step pressing
      technique and using sucrose as a pore former.
AB  - Macroporous calcium phosphate glass-ceramic with an initial glass composition of
      60CaO.30P2O5.3TiO2.7Na2O in mol% was successfully prepared by sintering the
      mixture compact consisting of calcium phosphate glass and sucrose powders, which
      was formed using a two-step pressing technique. After burning off the sucrose
      phase, a 3D interconnected macroporous structure was formed in the sintered body,
      in which the skeleton consisting of the calcium phosphate glass-ceramic
      (including beta-calcium pyrophosphate and beta-tricalcium phosphate as the
      crystalline phases) was transformed from the initial glass during the sintering.
      The macropores with several hundred microns in diameter and the large
      interconnection size (approximately 100 microm), which result from the
      controllably large-sized sucrose particles and the hot-pressing at a little
      higher temperature than the sucrose's melting point, are believed to meet the
      requirements for cell adhesion and bone tissue regeneration well. Moreover, in
      vitro dissolution behavior study indicates that the calcium phosphate glass
      ceramic is soluble to an acetic acid solution of pH 5-7. These, together with the
      simplicity and feasibility of the innovative fabrication method itself, show that
      the formed porous glass-ceramic has a promising potential for application to a
      scaffold for bone tissue engineering.

PMID- 15965745
TI  - Preparation of a reticulated polyurethane foam grafted with poly(acrylic acid)
      through atmospheric pressure plasma treatment and its lysozyme immobilization.
AB  - We successfully introduced peroxide groups onto the surface of PU(Polyurethane)
      foam(10 PPI) through one atmospheric pressure plasma treatment and sequentially
      grafted PAAc(poly(acrylic acid)) on the surface of PU through radical
      copolymerization. The plasma treatment can generate large amount of peroxides on
      the surface of PU foam and the peroxide groups act as initiators for further
      grafting of PAAc in the monomer solution. To introduce large amount of peroxides
      on the surface of PU foam, we studied the effect of plasma rf-power and treatment
      time on the maximum grafting of PAAc. Through this study, we found that the
      optimum plasma treatment condition was the rf-power of 100 W and the treatment
      time of 100 s. On the other hand, we also studied the effect of graft reaction
      conditions such as temperature, monomer concentration and reaction time on the
      change of grafting degree (GD). The GD increased with increasing temperature and
      increased with reaction time before it leveled off at 3 h after reaction started.
      At low concentration of AAc, the GD was very low but it showed a maximum at the
      monomer concentration between 60 and 70%. The surface of the modified PU foam was
      qualitatively and quantitatively analyzed through the use of FT-IR and weight
      measurement, respectively. We also observed the surface change before and after
      plasma induced graft co-polymerization through photo and SEM analysis. Finally,
      we confirmed that the PU foams grafted with PAAc successfully immobilized
      lysozyme and other proteins from hen egg white.

PMID- 15965746
TI  - Tyrosine derived polycarbonate membrane is useful for guided bone regeneration in
      rabbit mandibular defects.
AB  - Standardized bilateral through-and-through defects (12x6 mm) were created
      extraorally in the mandibular angle of 18 New Zealand White rabbits. Animals were
      divided in to three groups (n=6) according to the intended healing time. On the
      left side, defects were covered with a poly(desaminotyrosyl-tyrosine-ethyl ester
      carbonate) (PDTE carbonate) membrane wrapped around the inferior border of the
      mandible and fixed with bioabsorbable sutures. On the right side, the defects
      were filled with a mesh made of bioactive glass 13-93 and 3 wt% chitosan. The
      defects were covered with the same membranes. Periosteal flap was sutured over
      the membrane. Radiographically, bone ingrowth was seen in all specimens at 12
      weeks postoperatively. At 24 weeks, completely ossified area remained
      approximately at the same level as at 12 weeks, but the non-ossified area
      decreased to almost zero. However, the bioactive glass mesh did not improve the
      results. Nevertheless, enveloping the defect with PDTE carbonate membrane seemed
      to play a crucial role in new bone formation. Based on these results, we conclude
      that tyrosine polycarbonate is a promising new material for guided bone
      regeneration.

PMID- 15965747
TI  - Effect of thermal treatments on tensile strength of commercially cast pure
      titanium and Ti-6Al-4V alloys.
AB  - Heating titanium structures is assumed to relieve tensions induced by the casting
      process as well as possibly optimizing some mechanical properties. The aim of
      this investigation was to evaluate the effect of thermal treatments on tensile
      strength of commercially pure titanium (CP Ti) and Ti-6Al-4V alloy. Thirty
      dumbbell rods, with diameters of 3.0 mm at the central segment and lengths of 42
      mm, were cast for each metal using the Rematitan System. CP Ti and Ti-6Al-4V
      specimens were randomly divided into three groups of ten: a control group that
      received no thermal treatment and two test groups. One (T1) was heated at 750
      degrees C for 2 h and the other (T2) was annealed at 955 degrees C for 1 h and
      aged at 620 degrees C for 2 h. Tensile strength was measured with a universal
      testing machine (MTS model 810). Tensile strength means and standard deviations
      were statistically compared using a Kruskal-Wallis test at a alpha=0.05
      significance level. No statistically significant differences in tensile strength
      were observed among CP Ti groups. For the Ti-6Al-4V alloy, the control and T1
      groups revealed statistically higher tensile strengths when compared to the T2
      group, with no significant difference between the control and T1 groups.

PMID- 15965748
TI  - Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part II. Copolymers
      with positive and negative charges, polyelectrolyte complexes.
AB  - Crosslinked macroporous hydrogels based on 2-hydroxyethyl methacrylate (HEMA)-[2
      (methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl) copolymer, HEMA
      MOETACl-methacrylic acid (MA) terpolymer, and on a polyelectrolyte complex of
      HEMA-MA copolymer with poly(MOETACl) were prepared. All the hydrogels were
      prepared in the presence of fractionated sodium chloride particles. The hydrogels
      were characterized by the number of pores and the total volume of all pores in
      unit volume, the average volume and the average diameter of single pore.
      Morphology of the hydrogels was investigated by confocal and scanning electron
      microscopy. The hydrogels based on polyelectrolyte complexes were also
      characterized by chemical composition. Homogeneous (non-porous) hydrogels with
      the same composition as macroporous hydrogels were prepared and characterized by
      their biocompatibility.

PMID- 15965749
TI  - Processing of an apatite-mullite glass-ceramic and an hydroxyapatite/phosphate
      glass composite by selective laser sintering.
AB  - The work presented details the results of an investigation into the feasibility
      of using Selective Laser Sintering (SLS) to directly produce customised
      bioceramic implants. The materials used were bioactive in nature and included a
      glass-ceramic and a combination of hydroxyapatite and phosphate glass. The glass
      ceramic was selected from the range of apatite-mullite materials in the
      SiO2.Al2O3.CaO.CaF2.P2O5 series, due to their potentially suitable biological and
      mechanical properties. The hydroxyapatite and phosphate glass combination was
      chosen to allow an alternative production approach to be investigated. The
      viability of using both these materials with the SLS process was assessed and the
      process route and resulting material properties characterised using a variety of
      techniques including Differential Thermal Analysis (DTA), X-ray Diffraction (XRD)
      and Scanning Electron Microscopy (SEM). The results obtained indicate that it was
      possible to produce multiple layer components from both materials using the SLS
      process. The glass-ceramic materials could only be processed at very low scan
      speeds and powers, yielding relatively brittle components. It was though possible
      to produce parts from the hydroxyapatite and phosphate glass combination across a
      much wider range of parameters, producing parts which had a greater potential for
      possible implant production.

PMID- 15965750
TI  - Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part III. Hydrogels
      as carriers for immobilization of proteins.
AB  - Four series of macroporous hydrogels based on crosslinked copolymers of 2
      hydroxyethyl methacrylate (HEMA)-sodium methacrylate (MANa), copolymer HEMA-[2
      (methacryloyloxy)ethyl]trimethylammonium chloride (MOETACl), terpolymer HEMA-MANa
      MOETACl and on a polyelectrolyte complex were used as carriers for immobilization
      of proteins, chicken egg white albumin and avidin. The adsorption capacity of the
      hydrogels for the two proteins, kinetics and pH dependence of albumin adsorption
      and desorption were studied. The morphology of the hydrogels with and without
      immobilized albumin was studied by low-vacuum scanning electron microscopy.

PMID- 15965751
TI  - Nonlinear control for algae growth models in the chemostat.
AB  - This paper deals with output feedback control of phytoplanktonic algae growth
      models in the chemostat. The considered class of model is of variable yield type,
      meaning that the ratio between the environmental nutrient absorption rate and the
      cells' growth rate varies, which is different from classical bioprocesses
      assumptions. On the basis of weak qualitative hypotheses on the analytical
      expressions of the involved biological phenomena (which guarantee robustness of
      the procedure toward modeling uncertainties) we propose a nonlinear controller
      and prove its ability to globally stabilize such processes. Finally, we
      illustrate our approach with numerical simulations and show its benefits for
      biological laboratory experiments, especially for ensuring persistence of the
      culture facing classical experimental problems.

PMID- 15965752
TI  - Sex and environmental sensitivity in blue tit nestlings.
AB  - In birds and mammals with sexual size dimorphism (SSD), the larger sex is
      typically more sensitive to adverse environmental conditions, such as food
      shortage, during ontogeny. However, some recent studies of altricial birds have
      found that the larger sex is less sensitive, apparently because large size
      renders an advantage in sibling competition. Still, this effect is not an
      inevitable outcome of sibling competition, because several studies of other
      species of altricial birds have found the traditional pattern. We investigated if
      the sexes differ in environmental sensitivity during ontogeny in the blue tit, a
      small altricial bird with c. 6% SSD in body mass (males larger than females). We
      performed a cross-fostering and brood size manipulation experiment during 2 years
      to investigate if the sexes were differently affected as regards body size (body
      mass, tarsus and wing length on day 14 after hatching) and pre-fledging survival.
      We also investigated if the relationship between body size and post-fledging
      survival differed between the sexes. Pre-fledging mortality was higher in
      enlarged than in reduced broods, representing poor and good environments,
      respectively, but the brood size manipulation did not affect the mortality rate
      of males and females differently. In both years, both males and females were
      smaller on day 14 after hatching in enlarged as compared to reduced broods. In
      one of the years, we also found significant Sex x Experiment interactions for
      body size, such that females were more affected by poor environmental conditions
      than that of males. Body size was positively correlated with post-fledging
      survival, but we found no interactive effects of sex and morphological traits on
      survival. We conclude that in the blue tit, females (the smaller sex) are more
      sensitive to adverse environmental conditions which, in our study, was manifest
      in terms of fledgling size. A review of published studies of sex differences in
      environmental sensitivity in sexually size-dimorphic altricial birds suggests
      that the smaller sex is more sensitive than the larger sex in species with large
      brood size and vice versa.

PMID- 15965753
TI  - Phenological changes in the Northwestern Mediterranean copepods Centropages
      typicus and Temora stylifera linked to climate forcing.
AB  - Planktonic copepods play a major role in the fluxes of matter and energy in the
      marine ecosystem, provide a biological pump of carbon into the deep ocean, and
      play a role in determining fish recruitment. Owing to such ecological
      considerations, it is essential to understand the role that climate might play in
      the interannual variability of these organisms and the mechanisms by which it
      could modify the ecosystem functioning. In this study, a causal chain of
      meteorological, hydrological and ecological processes linked to the North
      Atlantic Oscillation (NAO) was identified in the Ligurian Sea, Northwestern
      Mediterranean. The forcing by the NAO drives most of the hydro-climatic
      variability during winter and early spring. Subsequently, interannual and decadal
      changes of the dominant copepods Centropages typicus and Temora stylifera were
      significantly correlated to the state of the hydro-climatic signal and tightly
      coupled to the NAO. Direct and indirect effects whose influence promoted
      phenological changes in the two copepod populations drove the species' responses
      to climatic forcing. Opposite responses of the analysed species were also
      highlighted by these results. While years characterized by the positive phase of
      the NAO leads to enhancement of the strength and the forward move of the C.
      typicus peak, they act negatively on the annual cycle of T. stylifera, the
      abundance of which drops twofold and the annual peak appears delayed in time. In
      contrast, low NAO years lead to high abundance of T. stylifera and a forward
      timing of its peak, and acts in turn negatively on the C. typicus annual cycle in
      both abundance (low) and timing (delayed). Owing to the synchronism between hydro
      climatic conditions and the NAO, and the major role of these species in the
      pelagic ecosystem of the studied area, these results provide key elements for
      interpreting and forecasting decadal changes of planktonic populations in the
      Ligurian Sea.

PMID- 15965754
TI  - Seasonal leaf dynamics across a tree density gradient in a Brazilian savanna.
AB  - Interactions between trees and grasses that influence leaf area index (LAI) have
      important consequences for savanna ecosystem processes through their controls on
      water, carbon, and energy fluxes as well as fire regimes. We measured LAI, of the
      groundlayer (herbaceous and woody plants <1-m tall) and shrub and tree layer
      (woody plants >1-m tall), in the Brazilian cerrado over a range of tree densities
      from open shrub savanna to closed woodland through the annual cycle. During the
      dry season, soil water potential was strongly and positively correlated with
      grass LAI, and less strongly with tree and shrub LAI. By the end of the dry
      season, LAI of grasses, groundlayer dicots and trees declined to 28, 60, and 68%
      of mean wet-season values, respectively. We compared the data to remotely sensed
      vegetation indices, finding that field measurements were more strongly correlated
      to the enhanced vegetation index (EVI, r (2)=0.71) than to the normalized
      difference vegetation index (NDVI, r (2)=0.49). Although the latter has been more
      widely used in quantifying leaf dynamics of tropical savannas, EVI appears better
      suited for this purpose. Our ground-based measurements demonstrate that
      groundlayer LAI declines with increasing tree density across sites, with savanna
      grasses being excluded at a tree LAI of approximately 3.3. LAI averaged 4.2 in
      nearby gallery (riparian) forest, so savanna grasses were absent, thereby greatly
      reducing fire risk and permitting survival of fire-sensitive forest tree species.
      Although edaphic conditions may partly explain the larger tree LAI of forests,
      relative to savanna, biological differences between savanna and forest tree
      species play an important role. Overall, forest tree species had 48% greater LAI
      than congeneric savanna trees under similar growing conditions. Savanna and
      forest species play distinct roles in the structure and dynamics of savanna
      forest boundaries, contributing to the differences in fire regimes, microclimate,
      and nutrient cycling between savanna and forest ecosystems.

PMID- 15965755
TI  - Elk winter foraging at fine scale in Yellowstone National Park.
AB  - The link between landscape properties and foraging decisions by herbivores
      remains unclear, but such knowledge is central to the understanding of plant
      herbivore dynamics. Our goal was to determine whether fine-scale foraging paths
      of free-ranging elk (Cervus canadensis) respond to spatial structure of habitats
      in Yellowstone National Park. During winter 2002 we gathered elk-foraging
      information by following snow tracks in open habitats located on hillsides and
      flat terrain. The 21 snow paths surveyed were comprised on average of 15 discrete
      snow craters connected to each other by relatively straight-line movements. Our
      analyses revealed two levels of selection: elk chose where to dig, and how much
      search effort to allocate at digging sites based on habitat characteristics. On
      hillsides, elk preferentially dug in areas of greater biomass of grasses and
      forbs, and simply walked through poorer sites without digging. Individuals also
      searched more intensively, creating larger craters, where food biomass was
      higher. On flat terrain, crater size decreased with snow depth and increased with
      snow density. Correlated random walk models usually were adequate to characterize
      elk movement on flat terrain, but not on hillsides. First, as the number of
      movements between local foraging areas increased, elk displacements on hillsides
      became shorter than expected from random patterns. This trend on hillsides was
      strongly influenced by interindividual variation in movement behavior. Second,
      elk tended to forage perpendicularly to aspect, resulting in horizontal
      displacements. Our study demonstrates that free-ranging elk adjust their foraging
      to fine-scale habitat structure.

PMID- 15965756
TI  - Evidence for oxidative stress in sugar maple stands growing on acidic, nutrient
      imbalanced forest soils.
AB  - Soil acidification and the disruption of nutrient cycles appear to be important
      factors that weaken sugar maple resistance to both abiotic and biotic stresses
      and predispose it to decline symptoms. Although connections between edaphic
      stress and decline symptoms have been identified, very little is known about the
      physiological and biochemical mechanisms that underlie this relationship. In this
      study, we tested the hypothesis that foliar nutrient imbalances impair the
      photosynthetic apparatus of sugar maple through oxidative stress. We examined
      leaf nutrition, photosynthesis and antioxidant enzyme activity (a biomarker of
      oxidative stress) from early June to late August in three-paired overstory sugar
      maple stands on Pennsylvania's Allegheny Plateau that contrast in soil nutrient
      availability according to slope position. Beginning in early June, trees on upper
      slopes (nutrient-poor) had significantly lower foliar Ca and Mg concentrations
      and significantly higher foliar Mn concentrations than trees on lower slopes.
      These differences increased throughout summer peaking in late August.
      Photosynthesis and antioxidant enzyme activity closely reflected changes in
      foliar nutrient status throughout the summer. In the latter half of the summer,
      leaf gas exchange and chlorophyll content were significantly lower and
      antioxidant enzyme activity was significantly higher in stands on upper slope
      soils. At the end of August, leaf nutrient imbalances corresponded with lower
      rates of photosynthesis and higher antioxidant enzyme activity, suggesting that
      foliar nutrient imbalances may impair sugar maple function through mechanisms of
      oxidative stress.

PMID- 15965757
TI  - Responding to inflammatory challenges is less costly for a successful avian
      invader, the house sparrow (Passer domesticus), than its less-invasive congener.
AB  - When introduced into new regions, invading organisms leave many native pathogens
      behind and also encounter evolutionarily novel disease threats. In the presence
      of predominantly novel pathogens that have not co-evolved to avoid inducing a
      strong host immune response, costly and potentially dangerous defenses such as
      the systemic inflammatory response could become more harmful than protective to
      the host. We therefore hypothesized that introduced populations exhibiting
      dampened inflammatory responses will tend to be more invasive. To provide initial
      data to assess this hypothesis, we measured metabolic, locomotor, and
      reproductive responses to inflammatory challenges in North American populations
      of the highly invasive house sparrow (Passer domesticus) and its less-invasive
      relative, the tree sparrow (Passer montanus). In the house sparrow, there was no
      effect of phytohemagglutinin (PHA) challenge on metabolic rate, and there were no
      detectable differences in locomotor activity between lipopolysaccharide (LPS)
      injected birds and saline-injected controls. In contrast, tree sparrows injected
      with PHA had metabolic rates 20-25% lower than controls, and LPS injection
      resulted in a 35% drop in locomotor activity. In a common garden captive breeding
      experiment, there was no effect of killed-bacteria injections on reproduction in
      the house sparrow, while tree sparrows challenged with bacteria decreased egg
      production by 40% compared to saline-injected controls. These results provide
      some of the first data correlating variation in immune defenses with invasion
      success in introduced-vertebrate populations.

PMID- 15965758
TI  - Pancaspase and cardiac function after infarction.

PMID- 15965759
TI  - Growth in liverworts of the Marchantiales is promoted by epiphytic
      methylobacteria.
AB  - Liverworts, the most basal lineage of extant land plants, have been used as model
      systems in the reconstruction of adaptations to life on land. In this study, we
      used gemmae (specialized propagules) that were isolated from mature gemma cups of
      two distantly related species of liverworts, Marchantia polymorpha L. and
      Lunularia cruciata L. (order Marchantiales). We show that methylobacteria (genus
      Methylobacterium), microbes that inhabit the surfaces of land plants where they
      secrete phytohormones (cytokinines), promote the growth of isolated gemmae
      cultivated on agar plates. As a control, two species of higher plants, maize (Zea
      mays L.) and sunflower (Helianthus annuus L.) were raised aseptically from
      sterile seeds (i.e., caryopses, achenes). Inoculation of these propagules with
      methylobacteria was without effect on growth in the above-ground phytosphere
      (expansion of stems and leaves). We conclude that normal development in
      Marchantia and Lunularia is dependent on (and possibly regulated by) epiphytic
      methylobacteria, whereas representative higher plants grow at optimal rates in
      the absence of these prokaryotic epiphytes.

PMID- 15965760
TI  - [Evaluation of risk assessment instruments for sex offenders].
AB  - In order to evaluate risk assessment instruments for sex offenders in Germany, we
      compared the predictive validity of the Static-99, HCR-20, SVR-20, and PCL-R
      scales for 134 sex offenders. The mean follow-up time was 9 years (range 1-340
      months), using the first entry into the National Register of Criminal Convictions
      as endpoint variable. For the estimate of predictive power, the area under the
      curve (AUC) of receiver operating characteristic (ROC) analysis was calculated.
      The AUC plots accurately identified violent or sexual recidivists and "false
      positives" at all scale levels. Comparing the predictive validity of these four
      instruments, the results favored Static-99. As for the limited sample size,
      differences between the assessment instruments were, however, not statistically
      significant. The ROC analysis for Static-99 showed that including treatment
      dropouts does not improve predictive accuracy (including dropouts: AUC 0.710;
      excluding dropouts: AUC 0.721). Kaplan-Meier survival analyses yielded highly a
      significant correlation to recidivism time point for two Static-99 and SVR-20
      risk categories. Higher-risk categories were related to earlier recidivism.
      However, relying on the Static-99 and SVR-20 alone showed false positive results:
      for up to two out of three sex offenders, they predicted recidivism which did not
      occur.

PMID- 15965761
TI  - Visual depth processing in Williams-Beuren syndrome.
AB  - Patients with Williams-Beuren Syndrome (WBS, also known as Williams Syndrome)
      show many problems in motor activities requiring visuo-motor integration, such as
      walking stairs. We tested to what extent these problems might be related to a
      deficit in the perception of visual depth or to problems in using this
      information in guiding movements. Monocular and binocular visual depth perception
      was tested in 33 patients with WBS. Furthermore, hand movements to a target were
      recorded in conditions with and without visual feedback of the position of the
      hand. The WBS group was compared to a group of control subjects. The WBS patients
      were able to perceive monocular depth cues that require global processing, but
      about 49% failed to show stereopsis. On average, patients with WBS moved their
      hand too far when no visual feedback on hand position was given. This was not so
      when they could see their hand. Patients with WBS are able to derive depth from
      complex spatial relationships between objects. However, they seem to be impaired
      in using depth information for guiding their movements when deprived of visual
      feedback. We conclude that the problems that WBS patients have with tasks such as
      descending stairs are not due to an inability to judge distance.

PMID- 15965762
TI  - Neural correlates of encoding and expression in implicit sequence learning.
AB  - In the domain of motor learning it has been difficult to separate the neural
      substrate of encoding from that of change in performance. Consequently, it has
      not been clear whether motor effector areas participate in learning or merely
      modulate changes in performance. Here, using a variant of the serial reaction
      time task that dissociated these two factors, we report that encoding during
      procedural motor learning does engage cortical motor areas and can be
      characterized by distinct early and late encoding phases. The highest correlation
      between activation and subsequent changes in motor performance was seen in the
      motor cortex during early encoding, and in the basal ganglia during the late
      encoding phase. Our results show that rapid encoding during procedural motor
      learning involves several distinct processes, and is represented primarily within
      motor system structures.

PMID- 15965763
TI  - Characterisation of variant alleles in the STR systems D2S1338, D3S1358 and
      D19S433.
AB  - We have observed three hitherto undescribed off-ladder alleles at three widely
      used STR loci. These were isolated, sequenced and designated as follows: allele
      10 (D2S1338, one case), allele 21 (D3S1358, two cases) and allele 6.2 (D19S433,
      six cases). These sequences are described in comparison to non-variant alleles,
      and their implications for the semi-automated STR analysis will be discussed.

PMID- 15965764
TI  - Y-chromosomal STR haplotypes in Chinese Uigur ethnic group.
AB  - We have already coamplified minimal haplotypes (DYS19, DYS389I, DYS389II, DYS390,
      DYS391, DYS392, DYS393, DYS385I/II), two additional loci, namely, DYS438, DYS439,
      and Amelogenin, in a single PCR using the Y-PLEX 12 kit. We investigated 107
      unrelated male individuals from the Uigur ethnic group and studied the allelic
      frequency distribution and haplotype diversity of 11 Y-chromosomal STRs. A number
      of 43 alleles (nine STR loci) and 27 phenotypes (including DYS385) were detected,
      with frequencies ranging from 0.0092 to 0.6296. A total of 103 haplotypes were
      identified, among which 99 were individual-specific and four haplotypes were
      found twice. The haplotype diversity for these 12 Y-STR loci was 0.9993.

PMID- 15965765
TI  - Modification of internal temperature regulation for cutaneous vasodilation and
      sweating by bright light exposure at night.
AB  - Bright light (BL) exposure at night leads to suppressed secretion of melatonin
      and an attenuated fall in internal temperature at rest from the night to the
      early morning. However, it is unknown at the present whether typical diurnal
      variations in reflex responses to thermal challenges are similarly affected by BL
      exposure at night. We investigated the control of cutaneous vasodilator and
      sweating responses to hyperthermia in the early morning after artificial BL
      exposure at night, compare with dim light (DL) exposure. Six subjects stayed
      awake in a semi-supine position under DL (120 lx) or BL (2800 lx) conditions
      between 21.00 and 04.30 h. Urine samples were collected at 04.30 h. Beginning at
      05.30 h, the lower legs were immersed for 50 min in 42 degrees C water. The
      subjects remained awake for 21 h until the end of hot water immersion. Urinary 6
      sulphatoxymelatonin levels following BL were significantly lower than after DL.
      Oesophageal temperature (T es) before heating was significantly higher following
      BL [36.41+/-0.10 (DL) vs. 36.55+/-0.09 (BL) degrees C]. The T es thresholds for
      the onset of cutaneous vasodilation and sweating were significantly higher with
      BL than with DL conditions (approximately 0.15 degrees C, respectively). We found
      that the internal temperature threshold for thermoregulatory control of cutaneous
      vasodilation and sweating responses to passive heating in the early morning can
      be modified by the level of light exposure the prior night. Thus both basal
      internal temperature and the regulation of internal temperature are modified by
      BL exposure at night.

PMID- 15965766
TI  - Economic impact of community-acquired and nosocomial lower respiratory tract
      infections in young children in Germany.
AB  - Data on the economic burden of lower respiratory tract infections (LRTI) in young
      children are lacking in Germany. The objective of the cost-of-illness study was
      to estimate the economic impact of community-acquired LRTI and nosocomial LRTI as
      well as of infections due to respiratory syncytial virus (RSV), parainfluenza
      viruses (PIV) and influenza viruses (IV). The economic analysis is part of the
      PRIDE study, a prospective, multi-centre, population-based epidemiological study
      on the impact of LRTI in children aged 0 to 36 months in Germany. The analysis
      includes children with community-acquired infections (1329 cases treated as
      outpatients, 2039 cases treated as inpatients) and nosocomial infections (90
      cases). Medical services consumed were generated by chart abstraction and
      parental expenses data by telephone interviews within four weeks after physician
      visit or hospitalisation. Costs were evaluated from following perspectives: third
      party payer, parent and society. Total costs for outpatient treatment are Euro
      123 per LRTI case. Stratified by virus type, total costs per case are Euro 163
      (RSV), Euro 100 (PIV) and Euro 223 (IV). Total costs per hospitalised LRTI case
      amount to Euro 2579. Stratified by virus type, total costs per case are Euro 2772
      (RSV), Euro 2374 (PIV) and Euro 2597 (IV). Total costs per nosocomial case are
      Euro 2814. Economic burden due to LRTI is Euro 213 million annually. It is
      concluded that treatment of LRTI in children up to age three causes a
      considerable economic burden in Germany. Presented results are the first data
      describing the economic burden of LRTI in young children assessed by means of the
      incidence data for Germany. This cost-of-illness study provides basic data for
      further decision-making, focusing on the economic assessment of preventive
      strategies for RSV, PIV and IV infections.

PMID- 15965769
TI  - Clear peritoneal effluent in a child on CCPD with a phlegmonous appendicitis.
AB  - Peritonitis as a result of a perorated appendicitis is a rare but life
      threatening situation in a patient on peritoneal dialysis (PD). As far as we are
      aware, the combination of clear dialysate effluent and phlegmonous appendicitis
      in a patient on PD has not previously been described. We report a 16-year-old
      girl with acute onset of abdominal pain and vomiting who turned out to have
      phlegmonous appendicitis, despite having a clear dialysate effluent with normal
      cell count, and who subsequently developed E coli peritonitis after surgery.

PMID- 15965768
TI  - Apoptosis and proliferation in childhood acute proliferative glomerulonephritis.
AB  - Acute proliferative glomerulonephritis is characterized by glomerular
      hypercellularity that can be caused by many different etiologies and pathogenetic
      mechanisms. A balance between cell birth by mitosis and cell death by apoptosis
      is crucial. In this study, apoptosis and the regenerative activity
      (Ki67/apoptosis index) were investigated in acute proliferative
      glomerulonephritis. Thirty-five children with biopsy-proven acute proliferative
      glomerulonephritis and five controls with MCD were studied retrospectively.
      According to the clinical outcome, patients were divided into 2 groups: group 1
      (n =21) were patients with normal renal functions at follow-up; group 2 (n =8)
      were patients with end-stage renal failure or those who died. Immunohistochemical
      staining of proliferating cells (Ki67) was done. In situ end labeling of DNA was
      used to evaluate apoptosis. Glomerular cell apoptosis was 45% in the patients
      with acute proliferative glomerulonephritis and 3% in controls ( p <0.001).
      Apoptotic cells were identified in the tubulointerstitial compartment with higher
      and heavier immunostaining in patients than controls (p =0.001). Tubular
      proliferative index (= tubular proliferation/tubular apoptosis ratio) was
      significantly higher in group 1 patients than in group 2 patients (2.03+/-2%
      versus 0.32+/-0.6%, p =0.002). Tubulointerstitial regenerative ratio (=tubular
      proliferation/interstitial proliferation ratio) was significantly higher in
      controls than in patients (3.4+/-1.9 versus 1.52+/-0.8, p =0.01). In addition, it
      was significantly increased in group 1 patients when compared with those in group
      2 patients (1.89+/-0.8 versus 0.73+/-0.2, p =0.001). Since 17 patients presented
      with postinfectious proliferative glomerulonephritis, which is known to exhibit
      better course, we also evaluated those parameters in patients with postinfectious
      proliferative glomerulonephritis separately. We found statistically significant
      differences only in the tubulointerstitial regenerative ratio, which was higher
      in postinfectious cases when compared with those in other cases [1.60
      interquartile range (IQR) 1.54 versus 1.22 IQR 1.26, respectively, p =0.003]. In
      conclusion, tubular proliferative index and tubulointerstitial regenerative ratio
      might be useful parameters for predicting final functional outcome in acute
      proliferative glomerulonephritis. Further studies, however, are still needed to
      clarify the importance of these histopathological parameters.

PMID- 15965770
TI  - Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient.
AB  - Fosphenytoin is indicated for the treatment of generalized convulsions and
      seizures occurring during neurosurgery. Metabolites of fosphenytoin include
      phenytoin, phosphate, and formaldehyde. The drug monograph recommends caution in
      administering fosphenytoin to patients in whom phosphate restriction is
      necessary. Additionally, fosphenytoin has altered pharmacokinetics in end-stage
      renal disease patients. We report a 17-year old African-American male with end
      stage renal disease who developed acute hyperphosphatemia to 3.9 mmol/L (12.1
      mg/dL) following the intravenous administration of 1000 mg of fosphenytoin for an
      idiopathic complex partial seizure. To our knowledge, this is the first report of
      acute hyperphosphatemia due to fosphenytoin administration. Due to this risk of
      hyperphosphatemia, we recommend that fosphenytoin should be used with caution in
      the end-stage renal disease population.

PMID- 15965771
TI  - Eighteen-year follow-up of a patient with partial hypoxanthine
      phosphoribosyltransferase deficiency and a new mutation.
AB  - Hypoxanthine phosphoribosyltransferase (HPRT) deficiency is an inherited
      disorder. Complete deficiency of HPRT activity is phenotypically expressed as the
      devastating Lesch-Nyhan syndrome. Partial HPRT deficiency usually causes
      hyperuricemia, precocious gout, and uric acid nephrolithiasis. We describe an 18
      year follow-up of a 5-year old boy with partial HPRT deficiency and report a
      novel mutation in his HPRT gene. He presented with overproduction of uric acid
      and passage of uric acid renal stones, and without gout or neurological and
      behavioral abnormalities. Treatment with allopurinol, adequate hydration, urinary
      alkalization, and a low-purine diet was started. No subsequent nephrolithiasis
      has occurred. After 18-year of this therapy his physical and neuropsychological
      status were normal, merely his glomerular filtration rate (GFR, normal 97-137 mL
      min(-1)/1.73 m(2)) fell from normal to 65.1 mL min(-1). The most likely cause of
      initial renal impairment in our patient is uric and/or xanthine crystalluria. A
      missense and transition mutation 169A>G (57ATG>GTG, 57met>val) in exon 3 of the
      patient's HPRT gene was identified and the mother was the carrier of the
      mutation. As far as we are aware, the identified mutation has not previously been
      reported. We named the mutant HPRT Maribor.

PMID- 15965772
TI  - Congenital nephrotic syndrome responsive to angiotensin-converting enzyme
      inhibition.
AB  - Congenital nephrotic syndrome is a severe disorder caused by increased
      permeability of the glomerular capillary leading to massive proteinuria.
      Typically, this disorder presents in the first three months and is caused by
      inherited mutations in genes encoding structural proteins of the podocyte slit
      membrane and, as such, is usually irreversible. Medical management is often
      insufficient to stem the enormous losses of protein, and the patients require
      nephrectomies. Here, we present results for a patient with congenital nephrotic
      syndrome of unknown etiology which responded to treatment with an angiotensin
      converting enzyme inhibitor alone. The patient's proteinuria relapsed when the
      medication was stopped, but went into complete remission after restarting
      treatment. This remarkable response is discussed in the light of recent
      investigations into the effect of angiotensin II on podocyte integrity.

PMID- 15965774
TI  - [Solitary abscessing osteomyelitis of the mandibular condyle. A rarity].
AB  - CASE REPORT: We report on a rare case of secondary chronic osteomyelitis of the
      left condyle. Haemophilus aphrophilus could be isolated from the abscess
      material. The condyle was resected and reconstructed with an endoprosthesis in
      the same operation. DISCUSSION: Possible causes of the rare location of secondary
      chronic osteomyelitis are assembled in a review of the literature and compared
      with the actual case. CONCLUSION: We suggest the inoculation of microorganisms
      through the needle of a local anesthetic injection, bacterial contamination
      during the tooth extraction, or bacteremia following the dental extraction to be
      possible causes for the infection.

PMID- 15965775
TI  - Successful treatment of a ruptured infected aneurysm of the lumbar artery with
      transcatheter embolization.
AB  - We report a patient who had an infected aneurysm of the lumbar artery caused by
      prolonged psoas abscess-forming spondylitis due to methicillin-resistant
      Staphylococcus aureus and who was treated successfully with transcatheter
      arterial embolization. This case suggests that an infected aneurysm can be
      treated successfully by transcatheter arterial embolization in emergent
      situations (active bleeding or septicemia) even if surgery is contraindicated.

PMID- 15965773
TI  - [Condylar metastasis. Review of the literature and report of a case].
AB  - BACKGROUND: Metastases in the mandibular condyle are rare. A survey of the
      literature showed that only 23 of 69 selected cases qualified under the criteria
      of Meyer and Shklar. REPORT OF A CASE: A 48-year-old white male suffering from a
      previously operated lung carcinoma was referred due to pain and discomfort in the
      left TMJ. A solitary condylar metastasis of the mandible was revealed. Because of
      diffuse tumorous infiltration into periarticular tissue, irradiation treatment
      was performed. During the long-term follow-up growth of additional skeletal
      metastases occurred. DISCUSSION: The course of condylar metastases in general is
      similar to other metastases involving the jaw. Breast cancer as the primary tumor
      is most frequent, followed by lung cancer. There are no specific clinical or
      radiological parameters leading to diagnosis. The clinician should take a
      potential metastasis into account when dealing with TMJ complaints, radiological
      oddities, and medical history of malignant tumors. For proper treatment planning,
      diagnosis should be based on histology. Since the diagnosis of metastasis is
      usually made at an advanced stage of disease, therapy will be mainly intended as
      palliative.

PMID- 15965776
TI  - Comparison of contrast-enhanced power Doppler ultrasound (Levovist) and computed
      tomography in alveolar echinococcosis.
AB  - BACKGROUND: To date, no study has compared unenhanced and contrast-enhanced
      (Levovist) power Doppler ultrasound with three-phase helical computed tomography
      (CT) for the analysis of the vascularization of hepatic lesions in patients who
      have alveolar echinococcosis. METHODS: Fifteen patients (11 female and four male;
      average age, 45.8 years) with confirmed Echinococcus multilocularis infection
      underwent unenhanced and contrast-enhanced (Levovist) power Doppler ultrasound (2
      to 5-MHz transducer head) and three-phase helical CT. The largest identified
      lesion in each patient was studied. RESULTS: CT visualized vascularization
      peripheral or central to the largest echinococcal lesions in 11 of 15 patients.
      Vascularization in the area of the echinococcal lesions was not visualized by
      unenhanced or contrast-enhanced power Doppler ultrasound in any of the 15
      patients studied. CONCLUSION: Three-phase helical CT visualizes the
      vascularization associated with Echinococcus multilocularis lesions in the liver.
      Neither unenhanced nor contrast-enhanced ultrasound in power mode is suitable for
      this application.

PMID- 15965777
TI  - Hepatosplenic brucelloma: clinical presentation and imaging features in six
      cases.
AB  - BACKGROUND: We conducted a retrospective analysis of the clinical presentation
      and the computed tomographic (CT) and ultrasound (US) findings in six episodes of
      hepatosplenic brucelloma in five patients. METHODS: In four episodes, the
      diagnosis was based on clinical history, serology, and characteristic imaging
      findings. In the other two episodes in the same patient, the diagnosis was
      suspected after a biopsy was taken. CT was performed in all six cases and US in
      five. RESULTS: On US, brucellomas were iso- or hypoechogenic with the liver.
      Hyperechogenic masses were seen in one patient. Brucellomas were very poorly
      defined and contained small scattered cystic areas. All lesions showed central or
      marginal gross focal calcification, except multiple lesions in one patient.
      Contrast-enhanced CT showed predominantly solid masses with irregular borders and
      fine or thick enhancing trabeculations separating hypodense solid areas and/or
      small cystic areas. Two patients showed transdiaphragmatic lung invasion by
      brucelloma, a complication not previously published. CONCLUSION: In regions where
      brucellosis is endemic, brucelloma should be included in the differential
      diagnosis if a hepatic or splenic mass with irregular borders and central or
      marginal gross focal calcification is detected, and contrast-enhanced CT shows
      enhancing trabeculations that separate hypodense solid areas and/or small liquid
      collections.

PMID- 15965778
TI  - Magnetic resonance T1 gradient-echo imaging in hepatolithiasis.
AB  - BACKGROUND: We examined the role of magnetic resonance T1-weighted gradient-echo
      (MRT1-GE) imaging in hepatolithiasis. METHODS: MRT1-GE, precontrast computed
      tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) of 10
      patients with hepatolithiasis were compared for their diagnostic accuracies in
      the detection and localization of intrahepatic calculi. The diagnosis of
      hepatolithiasis was confirmed by surgery. For localization of the stone, we
      divided the bile ducts into six areas: right and left hepatic ducts and bile
      ducts of the lateral, medial, right anterior, and right posterior segments of the
      liver. Chemical analysis of the stones was performed in eight patients. RESULTS:
      The total number of segments proved by surgery to contain stones was 18. Although
      not significantly different, the sensitivity of MRT1-GE was 77.8% (14 of 18
      segments), higher than that of MRCP (66.7%, 12 of 18 segments) and that of CT
      (50%, nine of 18 segments). The sensitivity of magnetic resonance imaging (MRCP +
      MRT1) was significantly higher than that of CT (p < 0.01). Multiple logistic
      regression analysis showed that the result of surgery was significantly affected
      only by the result of magnetic resonance imaging. On MRT1-GE, all the depicted
      stones appeared as high-intensity signal areas within the low-intensity bile duct
      irrespective of their chemical composition. CONCLUSION: MRT1-GE imaging provides
      complementary information concerning hepatolithiasis.

PMID- 15965779
TI  - Malignant biliary obstruction: value of imaging findings.
AB  - This review focuses on the clinical impact of different modalities to image
      primary and secondary malignant biliary obstruction. The detection and staging of
      cancers of the pancreatic and biliary tract are best accomplished with endoscopic
      ultrasound, contrast-enhanced computed tomography, and magnetic resonance
      cholangiopancreatography. Three-dimensional ultrasound is a new noninvasive
      method that may be used increasingly as an initial test to select patients who
      require further diagnostic evaluation by magnetic resonance
      cholangiopancreatography or therapeutic endoscopic retrograde
      cholangiopancreatography. All-in-one computed tomography including three
      dimensional reconstructions of the biliary tree may be competitive against all-in
      one magnetic resonance imaging for diagnosis and staging of pancreatic tumors.
      Magnetic resonance cholangiopancreatography is excellent for identifying the
      presence and the level of biliary obstruction. With newer diagnostic imaging
      technologies emerging, endoscopic retrograde cholangiopancreatography is evolving
      into a predominantly therapeutic procedure.

PMID- 15965780
TI  - Diffuse esophageal stricture secondary to esophageal lichen planus.
AB  - There are many well-known causes of diffuse esophageal stricture, including lye
      burns, reflux, radiation, and several mucocutaneous diseases. We report a case of
      esophageal stricture secondary to lichen planus. Esophageal lichen planus is rare
      and frequently mistaken for other more common disorders such as gastroesophageal
      reflux disease, which delays diagnosis and appropriate treatment, but it should
      be considered in female patients with cutaneous and oral lichen planus.

PMID- 15965783
TI  - Novel paternally expressed intergenic transcripts at the mouse Prader
      Willi/Angelman Syndrome locus.
AB  - Gene expression profiling was performed on central nervous system (CNS) tissue
      from neonatal mice carrying the T9H translocation and maternal or paternal
      duplication of proximal Chromosomes 7 and 15. Our analysis revealed the presence
      of two novel paternally expressed intergenic transcripts at the Prader
      Willi/Angelman Syndrome (PW/AS) locus. The transcripts were termed Pec2 and Pec3,
      for paternally expressed in the CNS. Imprinting of these transcripts was
      confirmed by sequencing of RT-PCR products in F(1) hybrids between Mus musculus
      musculus C57BL/6 and Mus musculus castaneus, following identification of single
      nucleotide polymorphisms between the two strains. Imprinting of Pec2 was also
      confirmed by Northern blot analysis. The two transcripts are separated by 0.5 Mb
      and are transcribed in the same orientation. They are located in a long
      interspersed transposable element (LINE)-rich region midway between the PW/AS
      imprinting center and the paternally expressed genes Ndn, Magel2, and Mkrn3,
      which are under imprinting center control. Our analysis also revealed imprinting
      of Magel2, Mkrn3, Ndn, Ube3a, and Usp29, as well as Pec2 and Pec3, in embryonic
      brain 15.5 dpc, and provided a survey of biallelically expressed genes on
      proximal Chrs 7 and 15 in embryonic and neonatal CNS.

PMID- 15965784
TI  - Evaluation of an FRDA-EGFP genomic reporter assay in transgenic mice.
AB  - Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by
      a GAA trinucleotide expansion in the first intron of the Friedreich ataxia gene
      (FRDA) that causes reduced synthesis of frataxin, a mitochondrial protein likely
      to be involved in biosynthesis of iron-sulfur clusters. This leads to increased
      oxidative stress, progressive loss of large sensory neurons, and hypertrophic
      cardiomyopathy. To elucidate the mechanisms regulating FRDA expression and to
      develop an in vivo assay for agents that might upregulate FRDA expression in a
      therapeutically relevant manner, we have generated transgenic mice with a BAC
      genomic reporter construct consisting of an in-frame fusion between FRDA and the
      gene coding for enhanced green fluorescent protein (EGFP). Production of full
      length frataxin-EGFP fusion protein was demonstrated by immunoblotting. EGFP
      expression was observed as early as day E3.5 of development. Most tissues of
      adult transgenic mice were fluorescent. The level of FRDA-EGFP expression in
      peripheral blood, bone marrow, and cells obtained from enzymatically
      disaggregated tissues was quantitated by flow cytometry. There was a twofold
      increase in EGFP expression in mice homozygous for the transgene when compared to
      hemizygous mice. These transgenic mice are a valuable tool for the examination of
      spatial and temporal aspects of FRDA gene expression and for the preclinical
      evaluation of pharmacological inducers of FRDA expression in a whole-animal
      model. In addition, tissues from these mice should also be valuable for stem cell
      transplantation studies.

PMID- 15965785
TI  - Quantitative trait loci for proteinuria in the focal glomerulosclerosis mouse
      model.
AB  - The FGS/Kist strain of mice, a new animal model for focal glomerulosclerosis
      (FGS) in humans, was previously established by recurrent selection for high
      proteinuria, which is a principal marker of FGS, from descendants of CBA/Nga and
      RFM/Nga strains. We performed a genome-wide scan for quantitative trait loci
      (QTLs) affecting proteinuria in a population of 356 backcross progeny derived
      from a cross between FGS/Kist and the standard normal strain, C57BL/6J. Five
      proteinuria QTLs (Ptnu1-5) were detected at the genome-wide 5% or less level.
      Ptnu1 and Ptnu2, located on Chromosomes (Chrs) 8 and 17, respectively, had main
      effects on proteinuria and also interacted epistatically with each other.
      However, Ptnu3 on Chr 9 and Ptnu4 and Ptnu5 both on Chr 15 had epistatic
      interaction effects only. Except for the epistatic interaction effect of Ptnu4
      and Ptnu5, all alleles derived from FGS/Kist were responsible for the high
      proteinuria. These results indicated that the genetic control of proteinuria is
      complex and the identified QTLs may provide new insights into the pathogenesis of
      FGS in mice as well as in humans.

PMID- 15965786
TI  - Single and multiple congenic strains for hydrocephalus in the H-Tx rat.
AB  - The H-Tx rat has fetal-onset hydrocephalus with a complex mode of inheritance.
      Previously, quantitative trait locus mapping using a backcross with Fischer F344
      rats demonstrated genetic loci significantly linked to hydrocephalus on
      Chromosomes 10, 11, and 17. Hydrocephalus was preferentially associated with
      heterozygous alleles on Chrs 10 and 11 and with homozygous alleles on Chr 17.
      This study aimed to determine the phenotypic contribution of each locus by
      constructing single and multiple congenic strains. Single congenic rats were
      constructed using Fischer F344 as the recipient strain and a marker-assisted
      protocol. The homozygous strains were maintained for eight generations and the
      brains examined for dilated ventricles indicative for hydrocephalus. No congenic
      rats had severe (overt) hydrocephalus. A few pups and a significant number of
      adults had mild disease. The incidence was significantly higher in the C10 and
      C17 congenic strains than in the nonhydrocephalic F344 strain. Breeding to F344
      to make F.H-Tx C10 or C11 rats heterozygous for the hydrocephalus locus failed to
      produce progeny with severe disease. Both bicongenic and tricongenic rats of
      different genotype combinations were constructed by crossing congenic rats. None
      had severe disease but the frequency of mild hydrocephalus in adults was similar
      to congenic rats and significantly higher than in the F344 strain. Rats with
      severe hydrocephalus were recovered in low numbers when single congenic or
      bicongenic rats were crossed with the parental H-Tx strain. It is concluded that
      the genetic and epigenetic factors contributing to severe hydrocephalus in the H
      Tx strain are more complex than originally anticipated.

PMID- 15965787
TI  - Association of an Agouti allele with fawn or sable coat color in domestic dogs.
AB  - The type of pigment synthesized in mammalian hair, yellow-red pheomelanin or
      black-brown eumelanin, depends on the interaction between Agouti protein and the
      Melanocortin 1 receptor. Although the genetics of pigmentation is broadly
      conserved across most mammalian species, pigment type-switching in domestic dogs
      is unusual because a yellow-tan coat with variable amounts of dark hair is
      thought to be caused by an allele of the Agouti locus referred to as fawn or
      sable (a(y)). In a large survey covering thirty seven breeds, we identified an
      Agouti allele with two missense alterations, A82S and R83H, which was present
      (heterozygous or homozygous) in 41 dogs (22 breeds) with a fawn or sable coat,
      but was absent from 16 dogs (8 breeds) with a black-and-tan or tricolor
      phenotype. In an additional 33 dogs (14 breeds) with a eumelanic coat, 8 (German
      Shepherd Dogs, Groenendaels, Schipperkes, or Shetland Sheepdogs) were homozygous
      for a previously reported mutation, non-agouti R96C; the remainder are likely to
      have carried dominant black, which is independent of and epistatic to Agouti.
      This work resolves some of the complexity in dog coat color genetics and provides
      diagnostic opportunities and practical guidelines for breeders.

PMID- 15965788
TI  - Y chromosome haplotype analysis in purebred dogs.
AB  - In order to evaluate the genetic structure of purebred dogs, six Y chromosome
      microsatellite markers were used to analyze DNA samples from 824 unrelated dogs
      from 50 recognized breeds. A relatively small number of haplotypes (67) were
      identified in this large sample set due to extensive sharing of haplotypes
      between breeds and low haplotype diversity within breeds. Fifteen breeds were
      characterized by a single Y chromosome haplotype. Breed-specific haplotypes were
      identified for 26 of the 50 breeds, and haplotype sharing between some breeds
      indicated a common history. A molecular variance analysis (AMOVA) demonstrated
      significant genetic variation across breeds (63.7%) and with geographic origin of
      the breeds (11.5%). A network analysis of the haplotypes revealed further
      relationships between the breeds as well as deep rooting of many of the breed
      specific haplotypes, particularly among breeds of African origin.

PMID- 15965789
TI  - Characterization of Pisrt1/Foxl2 in Ellobius lutescens and exclusion as sex
      determining genes.
AB  - The rodent Ellobius lutescens is an exceptional mammal which determines male sex
      constitutively without the SRY gene and, therefore, may serve as an animal model
      for human 46,XX female-to-male sex reversal. It was suggested that other factors
      of the network of sex-determining genes determine maleness in these animals.
      However, some sex-determining genes like SOX9 and SF1 have already been excluded
      by segregation analysis as primary sex-determining factors in E. lutescens. In
      this work, we have cloned and characterized two genes of the PIS (polled intersex
      syndrome) gene interval, which were reported as candidates in female-to-male sex
      reversal in hornless goats recently. The genes Foxl2 and Pisrt1 from that
      interval were identified in E. lutescens DNA and mapped to Chromosome 8. We have
      excluded linkage of Foxl2 and Pisrt1 loci with the sex of the animals. Hence, the
      involvement of this gene region in sex determination may be specific for goats
      and is not a general mechanism of XX sex reversal or XX male sex determination.

PMID- 15965790
TI  - [Drug therapy in the aged].

PMID- 15965791
TI  - [Drug use and self-perceived health as reported by community-dwelling elderly
      persons in Hamburg].
AB  - Self-perceived health as reported by elderly persons is of prognostic value and
      corresponds with morbidity and mortality. In the present study, information about
      the utilisation of medication, visits to the doctor, and self-perceived health
      was provided by standardised self-reports. The study sample included 804
      independent community-dwelling persons 60 years and older. These persons were
      recruited from the patient lists of 14 general practices in Hamburg. Exclusion
      criteria were dementive disorders and the need of personal care. On average,
      there were 3 prescribed drugs and 1 over-the-counter medication per person. The
      number of medications corresponds to a mean of 2 chronic disorders. Almost 50% of
      the participants reported suffering from pain, with more than one-third rating
      their pain intensity as moderate or high. Furthermore, nearly half of the study
      population stated their self-reported health as moderate or poor, and one-fifth
      reported symptoms of depressed mood. There were discrepancies between the reports
      of pain or depressed mood and the corresponding use of medication. It seems that
      self-reported symptoms and self-perceived health in elderly persons should be
      considered more often in drug prescribing.

PMID- 15965792
TI  - Acute poisoning in old and very old patients: a longitudinal retrospective study
      of 5883 patients in a toxicological intensive care unit.
AB  - Although morbidity and mortality of acute poisoning are increased in elderly
      compared to younger patients, little has been published on this topics in the
      last years (Medline search). To investigate the influence of age on the clinical
      course of acute poisoning with different toxic agents, a longitudinal
      retrospective study at the Toxicological Intensive Care Unit (ICU) of the 2nd
      Department of Internal Medicine (Klinikum Nurnberg, Germany) was performed.A
      total of 5883 patients treated at our toxicological ICU were enrolled into the
      study, including all patients of the years 1982, 1992, and 1997. These three
      years were selected to investigate possible time-dependent changes of
      intoxication characteristics and quality of therapy at our ICU over a time span
      of 15 years. For each patient the following data were obtained from a
      standardized toxicological record: age, gender, toxic agents responsible for
      acute poisoning, and length of stay at the toxicological ICU. For a subgroup of
      3740 patients, the cause of acute poisoning and the clinical outcome was also
      recorded. As compared with younger patients, mean length of stay at the ICU,
      indicating a more serious course of acute poisoning, was prolonged in elderly
      and, i. e., in very old patients (p <0.001). However, this prolongation of time
      at the ICU was only observed in elderly patients poisoned with drugs or with
      mixed poisoning including drugs, while mean length of stay was not prolonged in
      elderly patients poisoned with alcohol, with illegal drugs, chemicals,
      animal/plant poison, or other toxic agents. Patients with the highest risk of
      dying in the ICU after acute poisoning were elderly patients attempting suicide
      with drugs. Mortality in 3740 patients with acute poisoning was 0.24%, while it
      was 2.17% in the 184 patients being 65 years old or older. Thus, mortality was 9
      fold higher in the elderly. Mean length of stay at the ICU decreased
      significantly from 1982 to 1992 and to 1997 (p <0.001) indicating an improvement
      of the therapeutical ICU management of acute poisoning and/or less dangerous
      toxic agents (i. e. less barbiturates). The age-dependent increase of the length
      of stay at the ICU until very old age (> 80 years) was most pronounced in 1982
      and also declined markedly until 1997.Age, suicide attempt, and ingestion of
      (multiple) drugs seem to be risk factors for a higher mortality and a prolonged
      stay in the ICU after acute poisoning. Although in general the clinical course
      after poisoning has more complications and an impaired prognosis in old age, each
      category of toxic agents (drugs, alcohol, chemicals, etc.) has its own special
      "risk profile" for elderly patients. However, due to advances in modern ICU
      medicine the general prognosis of acute poisoning is good in old and even in
      oldest old patients.

PMID- 15965793
TI  - Medication for older people--aspects of rational therapy from the general
      practitioner's point of view.
AB  - This paper discusses GP perspectives on the principles underlying rational
      pharmacotherapy for older people. The rising use of prescription medicine forces
      the GP to balance the benefit of evidence group-based appropriate drug use
      against the problems arising when medication is given to older people and to
      consider different approaches when evaluating evidence of risk and benefit for
      the individual. Old people are facing a considerable risk of adverse drug
      reactions and recent initiatives, including the Continuous Medical Educational
      Efforts Programme, address issues of inappropriate prescribing practices. The
      authors recommend and present tools enabling the GP to focus on 'the core
      prescribing situation'. The logistics to optimise medication including
      compliance, the use of modern IT and better collaboration and communication
      between primary and secondary care are discussed. The authors state that a number
      of pharmacological regimens for older people are outperformed by non
      pharmacological treatment alternatives involving competent individualised
      counselling and public provision of easy (transportation) possibilities for
      joining centres offering staff and equipment for physical and social activity
      (including basal aids for hearing and sight).

PMID- 15965794
TI  - [Frequency, relevance, causes of and strategies for prevention of medication
      errors].
AB  - Drug therapy has led to major advances in medicine. The beneficial effects of
      drug therapy are coupled with the inevitable risk of adverse drug reactions
      especially in elderly patients. Many adverse drug reactions are preventable. The
      electronic health card that will be introduced in Germany starting in 2006 is
      designed to support electronic decision support to prevent medication errors.
      Studies have demonstrated that CPOES can reduce medication errors by 80%. The
      necessary steps to improve medication safety in Germany are outlined and
      discussed.

PMID- 15965795
TI  - The impact of social relationships on the maintenance of independence in advanced
      old age: findings of a Swiss longitudinal study.
AB  - The impact of social relationships on the maintenance of independence over
      periods of 12-18 months in a group of 306 octogenarians is assessed in this
      study. The study is based on the results of the Swilsoo (Swiss Interdisciplinary
      Longitudinal Study on the Oldest Old). Participants (80-84 years old at baseline)
      were interviewed five times between 1994 and 1999. Independence was defined as
      the capacity to perform without assistance eight activities of daily living. We
      distinguished in our analyses kinship and friendship networks and evaluated
      social relationships with the help of a series of variables serving as indicators
      of network composition and contact frequency. Logistic regression models were
      used to identify the short-term effects of social relationships on independence,
      after controlling for sociodemographic and health-related variables; independence
      at a given wave of interviews was interpreted in the light of social factors
      measured at the previous wave. Our analyses indicate that the existence of a
      close friend has a significant impact on the maintenance of independence
      (OR=1.58, p<0.05), which is not the case with the other variables concerning
      network composition. Kinship contacts were also observed to have a positive
      impact on independence (OR=1.12, p<0.01).

PMID- 15965796
TI  - [Nursing care assessment and decubitus ulcer. A data evaluation of nursing care
      in the MDK-WL].
AB  - PURPOSE: To detect the frequency and circumstances of sore ulcers in
      comparatively unselected patients of the German nursing care insurance who
      claimed for compensation. Setting Cross-sectional/case-control. METHODS: Data
      sampling and descriptive analysis. Assembled data were biometric data, level of
      the need of care, grade of sore ulcer, duration of sore ulcer, bedding materials
      and frequency of wound dressings of sore ulcer. RESULTS: In 97 622 out-patients
      and 32 059 patients from nursing care units, there were 3.2 and 6.4% sore ulcers,
      respectively, with diverse grades of severity present. Despite the difference in
      frequency of sore ulcers, no distinction in the nursing quality could be shown
      between out-patients and patients from nursery care units. Our data possibly
      suggested a lack with regard to evidence-based prophylaxis and treatment of sore
      ulcers in both groups. CONCLUSIONS: For both out-patients and patients from
      nursing care units, prophylaxis and treatment of sore ulcers could possibly be
      improved. Further studies will be needed to reveal the short-comings in nursing
      care and to map out strategies for improvement.

PMID- 15965800
TI  - [New aspects in the diagnosis and therapy of acute and chronic pulmonary
      hypertension].

PMID- 15965801
TI  - [Thrombolytic therapy in acute pulmonary embolism].
AB  - The debate about thrombolysis in acute pulmonary embolism (PE) as an adjunctive
      therapy to heparin is ongoing for about 35 years. Thrombolysis dissolves
      thromboemboli faster than heparin in combination with spontaneous lysis. So,
      thrombolysis achieves a faster normalization of the pulmonary artery pressure.
      Thrombolysis may be life-saving in patients with cardiogenic shock and in
      patients with hemodynamic instability due to massive PE. It is still on
      discussion whether patients with right heart strain who are hemodynamically
      stable should be treated with thrombolysis. Inconsistent definitions of right
      heart strain may be responsible for the lack of evidence for reducing mortality
      by thrombolysis. The authors' right heart score (R-S(Wacker)) enables physicians
      to describe the right heart strain in patients with PE quantitatively. The R
      S(Wacker) is of prognostic value with regard to in-hospital mortality and 6-month
      mortality. Patients with a normal to moderately elevated R-S(Wacker) have an
      excellent outcome (0% in-hospital mortality) and do not profit from thrombolysis.
      In patients with relevant right heart strain thrombolysis may be discussed,
      especially in combination with an elevation of the biomarkers troponin I or T and
      brain natriuretic peptide (BNP). Patients with intracardiac thromboemboli,
      especially in the presence of a patent foramen ovale, should receive
      thrombolysis, in selected cases surgery should be done. Therapy and therapy
      escalation are highly dependent on the time interval after diagnosis of PE:
      patients who survive the first 24 h and who are on heparin in therapeutic dosage
      without any interruption have a good prognosis. Therefore, therapy escalation
      after 24 h or even later should be an exception.

PMID- 15965802
TI  - [Surgical treatment for massive pulmonary embolism].
AB  - Surgical embolectomy for massive pulmonary embolism (PE) has become a rare
      procedure. Often, it is viewed as a last-chance option for patients undergoing
      cardiopulmonary resuscitation after massive PE. Thus thrombolytic therapy has
      become the treatment of choice. However, a significant proportion of patients
      suffers from residual obstruction after thrombolytic therapy and faces the
      development of chronic pulmonary hypertension. Therefore, some centers have
      regained interest in surgical embolectomy after improved risk stratification and
      reported very good results. Perioperative survival rates up to 89% have been
      reported. This was accomplished by surgery on the ECC-(extracorporeal circulation
      )supported, beating, normothermic heart and utilization of special instruments.
      These encouraging results have been confirmed by the authors and others in
      patients with stable systemic hemodynamics but moderate to severe right
      ventricular dysfunction. The more widespread use of surgical embolectomy seems
      warranted. A randomized, controlled trial is overdue to determine the benefits of
      this therapy in stable patients compared with thrombolytic therapy if "best
      practice" therapy is to be achieved for the patients' benefit.

PMID- 15965803
TI  - [Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary
      hypertension].
AB  - Bilateral pulmonary thromboendarterectomy has been recognized as the first-choice
      therapeutic option for patients with chronic thromboembolic pulmonary
      hypertension. With careful patient selection, meticulous surgical technique and
      careful postoperative management the surgical procedure has proven potentially
      curative for these often severely incapacitated patients in whom prognosis is
      otherwise poor. By means of pulmonary angiography and multislice CT correct
      diagnosis is established and the crucial question of operability determined.In
      the presence of significant exertional dyspnea and/or elevation of pulmonary
      vascular resistance surgery is indicated when the thromboembolic obstructions are
      determined accessible to surgical removal. Suboptimal surgical results may be
      obtained in patients with solely peripheral location of lesions, i. e., beginning
      at the bronchopulmonary segmental arteries, and correct patient selection becomes
      crucial especially in advanced stages of disease of very high pulmonary vascular
      resistance and presence of right heart failure.The surgical techniques are
      standardized with use of median sternotomy with cardiopulmonary bypass, deep
      hypothermia and periods of circulatory arrest and consist of complete dissection
      of the intimal layer of the pulmonary branches containing the thromboembolic
      lesions as a true endarterectomy technique.The reported operative mortality for
      pulmonary thromboendarterectomy differs in the literature between 4.5% and 23.5%
      and probably reflects not only the various experiences with this patient group
      but most likely also the disparate policies in patient selection. The authors'
      experience comprises 250 surgically treated patients with an operative mortality
      of 14.4%. The immediate hemodynamic and functional improvement of patients
      following successful thromboendarterectomy is excellent with further improvement
      during the first year. Pulmonary hypertension recurs over time in a few patients
      because of embolism, thrombosis or progression of reactive vasculopathy. However,
      the functional improvement and decrease of right ventricular afterload are
      persistent in the vast majority.Given the poor results of lung transplantation,
      this is not an alternative, and patients with chronic thromboembolic pulmonary
      hypertension should undergo thromboendarterectomy, preferably in the most early
      stage of their disease.

PMID- 15965804
TI  - [Pulmonary hypertension and lung transplantation].
AB  - BACKGROUND: With the development of effective drug treatment in the last 2
      decades, lung transplantation has become the final option in the management of
      pulmonary arterial hypertension (PAH). Its main advantage is the curative aspect
      with recovery of cardiopulmonary capacity. Scarcity of donor organs and chronic
      graft rejection, however, remain serious limitations to short- and long-term
      success, and emphasize the need for judicial patient selection. Timely
      presentation of the patient to the transplant center is of critical importance.
      INDICATION: Guidelines have been presented by the International Society for Heart
      and Lung Transplantation (ISHLT), the American Thoracic Society (ATS) and the
      American Society of Transplant Physicians (ASTP) in the year 1998. Selection
      criteria are clinical status (NYHA [New York Heart Association] > or = III and
      progressing, right heart insufficiency symptoms), hemodynamic data (mean
      pulmonary arterial pressure > 55 mmHg, systolic arterial pressure < 120 mmHg,
      cardiac index < 2 l/min/m2, central venous pressure > 15 mmHg, right heart
      function on echocardiography), and functional parameters (peak oxygen uptake < 10
      12 ml/kg/min, 6-min walk test [MWT] < 332 m). Functional parameters have been
      shown to correlate with a 1-year mortality of 40% with a 6-MWT < 332 m, of 50%
      with a peak oxygen uptake < 10.4 ml/kg/min, and of 70% with a systolic arterial
      pressure < 120 mmHg. Combinations of the above lead to a 1-year survival of 23%.
      Mean survival of patients with primary pulmonary hypertension (PPH) is 2.8 years
      and is reduced to 6 months, when NYHA IV is reached (National Institutes of
      Health-PPH Registry 2002). These data underline the potential survival benefit
      from transplantation for patients with advanced lung failure due to PAH.
      TRANSPLANTATION: Single lung, bilateral lung and heart-lung transplantation are
      the transplantation procedures available. Even though heart-lung transplantation
      was the first procedure to be performed in 1981, bilateral lung transplantation
      is the procedure most commonly performed at present. Choice of transplantation
      procedure should be made after thorough evaluation, taking the potential
      reversibility of right ventricular dysfunction after the operation into account
      (Figure 1). Hemodynamic instability from right and/or left ventricular failure,
      however, may complicate early postoperative management. Heart and lung
      transplantation should only be considered, if structural heart damage is present.
      Lung function improves immediately postoperatively and increases in the following
      6 months. Most patients have normal function studies 1 year after
      transplantation. STATISTICS: The Registry of the ISHLT (01/1982-06/2003) reports
      PAH as primary diagnosis in 4.2% of all lung transplantations (457/10,959) and
      24.3% (550/2,263) of all heart-lung transplantations. This corresponds to 1.1% of
      all single (66/5,793) and 7.6% of all bilateral lung transplantations
      (391/5,166). Single lung transplantation is associated with shorter ischemia,
      cardiopulmonary bypass and operation time. The procedure, however, is accompanied
      by ventilation/perfusion mismatch, a higher likelihood of reperfusion injury and
      less functional reserve in case of progressive chronic rejection. The advantages
      of bilateral lung transplantation are under discussion, particularly as 5-year
      survival seems to be higher in some centers. Heart and lung transplantation is
      reported to have similar results as bilateral lung transplantation (Table 1),
      showing survival advantages only in patients with Eisenmenger's syndrome or
      ventricular septal defect. Bilateral lung transplantation, therefore, is the
      procedure of choice at the Essen Transplant Center, provided donor organs are
      available. CONCLUSION: Thoracic transplantation has become a feasible therapeutic
      option in terminal PAH patients. Judicious patient selection, choice and timing
      of procedure are critical to a successful outcome.

PMID- 15965805
TI  - [Clinical and pharmacological testing of patients with pulmonary hypertension for
      treatment decision].
AB  - Pulmonary arterial hypertension (PAH) is a rare and rapidly progressing disease
      characterized by an increase in pulmonary resistance, which, if untreated,
      inevitably progresses to right ventricular heart failure and death. New treatment
      options were developed in the last 10 years. Endothelin receptor antagonists
      (ERAs) and prostanoids are an effective treatment with a better survival.
      Phosphodiesterase inhibitors (PDIs) are of a great interest, and first results in
      the treatment of patients are promising. PDIs are different in pulmonary
      selectivity and half-life.Right heart catheterization is the "gold standard" in
      the diagnosis of pulmonary hypertension. Direct classification of the pulmonary
      hypertension is feasible, and the effects of the drugs are directly measurable.
      The results of right heart catheterization are comparable for inhalative and oral
      drugs. New generations of drugs resulted in special testing protocols.
      Furthermore, individual concepts of therapy can be developed.

PMID- 15965806
TI  - [Emerging therapies for the treatment of pulmonary arterial hypertension].
AB  - Besides all progress in the therapy of pulmonary arterial hypertension over the
      past years, there is still no cure for this devastating disease. By introducing
      effective and nonparenteral medications (e. g., oral endothelin receptor
      antagonists [ERAs], inhaled prostanoids), quality of life, exercise tolerance and
      prognosis of patients have substantially improved. However, applicability of
      these therapies can be hampered by serious side effects and/or the necessity for
      elaborate application techniques. Whether selective ERAs--due to their
      specificity for the A-type receptor--have potential benefits over the
      nonselective ERA bosentan remains to be answered by the analysis of pivotal
      trials recently carried out with ambrisentan and sitaxsentan. Inhaled
      treprostinil can potentially have benefits over the already approved inhaled
      iloprost, related to its higher pulmonary selectivity as well as to the longer
      biological half-life. However, this has yet to be proven in long-term randomized
      controlled trials. In comparison to the previously mentioned substances, the
      selective phosphodiesterase-5 (PDE5) inhibitor sildenafil approached approval
      closest as new therapy for pulmonary arterial hypertension. Oral sildenafil has
      proven its efficacy as a selective pulmonary vasodilator in various forms of
      pulmonary hypertension. The results of the pivotal phase III trial have confirmed
      the strong efficacy and excellent tolerability of this substance. Combination
      therapies, despite all progress seen for single agents, can be regarded as the
      most promising therapeutic approach for the future. However, controlled
      randomized trials that are currently under consideration have to confirm this
      notion.

PMID- 15965807
TI  - Current therapy of pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) affects vascular proliferation and
      remodeling in small pulmonary arteries and results in right ventricular failure
      and death due to a progressive increase in pulmonary vascular resistance. Recent
      advances in understanding of the molecular mechanisms involved in PAH suggest
      that endothelial dysfunction plays a major role. Impaired production of
      vasoactive mediators, such as prostacyclin and nitric oxide, accompanied with
      prolonged overexpression of vasoconstrictors such as endothelin-1, affects
      vascular tone and reinforces vascular remodeling. As the latter substances
      represent logical pharmacological targets, new drugs affecting these mechanisms
      have evolved during the past 2 decades and led to umpteen placebo-controlled
      trials in bygone years. Prognosis and quality of life of patients suffering from
      PAH seem to improve due to these new treatment strategies resulting in a
      reduction of mortality and morbidity, but there is still a substantial need for
      further long-term and head-to-head trials.

PMID- 15965808
TI  - Pulmonary hypertension in advanced heart failure.
AB  - The diagnosis of pulmonary hypertension is easy during routine evaluation of
      patients with chronic heart failure by means of Doppler echocardiography.
      However, one must remember that an accurate hemodynamic characterization of the
      pulmonary circulation requires right heart catheterization to measure pulmonary
      vascular resistance and, if necessary, to test the reversibility of pulmonary
      hypertension. In addition, the importance of combining the right heart
      hemodynamic variables with a functional evaluation of the right ventricle is
      emphasized: in fact, the clinical impact of pulmonary hypertension in advanced
      heart failure patients (in terms of both exercise intolerance and prognosis)
      seems to be modulated by right ventricular function.

PMID- 15965809
TI  - [Assessment of cardiopulmonary function at rest and during exercise in patients
      with pulmonary hypertension].
AB  - Pulmonary hypertension is diagnosed by various investigations that are essential
      for making the diagnosis. Following a careful history and physical examination,
      an electrocardiogram, a chest X-ray, lung function studies, blood tests and an
      echocardiogram form the basis of the diagnostic algorithm. Following these
      studies, a right and sometimes additional left heart catheterization are carried
      out to establish the diagnosis and to perform acute vasodilator testing. Most of
      these studies are performed at rest. However, exercise studies are an important
      part of the functional assessment in this group of patients. Exercise capacity
      can be estimated by functional class, measured with the 6-min walk test or
      comprehensively assessed by cardiopulmonary exercise testing with gas exchange
      analysis. Once the diagnosis and etiology of pulmonary hypertension have been
      established, several parameters can predict outcome in these patients: functional
      class, right ventricular function, pulmonary hemodynamics, and certain laboratory
      parameters (uric acid, brain natriuretic peptide, troponin, endothelin-1). In
      addition, exercise parameters such as walking distance, peak oxygen uptake or
      peak systolic blood pressure can reliably predict prognosis in these patients.

PMID- 15965810
TI  - [Treatment algorithm for pulmonary arterial hypertension].
AB  - During the last decade, we have witnessed substantial improvements in the
      therapeutic options for pulmonary arterial hypertension (PAH), including true
      innovations targeting some of the mechanisms involved in the pathogenesis of this
      devastating disease. Intravenous epoprostenol was the first drug to improve
      symptoms and survival of patients with PAH. Novel prostanoids including
      subcutaneous treprostinil and inhaled iloprost also have beneficial effects in
      many patients, although their long-term efficacy is less well known. Among the
      newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase
      type 5 inhibitors have reshaped clinical practice. The endothelin receptor
      antagonist bosentan has been approved in many parts of the world and most current
      guidelines recommend this drug as first-line treatment for PAH. Novel endothelin
      receptor antagonists such as sitaxsentan and ambrisentan are currently being
      investigated. The phosphodiesterase type 5 inhibitor sildenafil is also being
      intensively studied in patients with pulmonary hypertension, and most of the
      available data look promising, although approval for PAH is still pending. Other
      phosphodiesterase type 5 inhibitors have not yet undergone extensive study in
      PAH. However, PAH is a complex disorder and targeting a single pathway cannot be
      expected to be uniformly successful. Thus, combining substances with different
      modes of action is expected to improve symptoms, hemodynamics and survival in PAH
      patients, although combination therapy has yet to undergo the scrutiny of large
      randomized clinical trials.Based on the available data, several guidelines for
      the diagnostic and therapeutic approach to PAH have been published recently.
      These guidelines have incorporated treatment algorithms, which, fortunately, are
      virtually identical. The present review article summarizes the current guidelines
      to the management of patients with PAH.

PMID- 15965811
TI  - [Can PCI with drug-eluting stents replace coronary artery bypass surgery? A
      comparative economic analysis regarding both therapeutic options based on
      clinical 12-month data reflecting the German social health care insurance
      system].
AB  - BACKGROUND AND PURPOSE: It is generally known and accepted that percutaneous
      coronary intervention (PCI) has undergone a patient-relevant innovation with the
      introduction of drug-eluting stents (DES): prospective, randomized, controlled
      studies with a primary clinical endpoint have shown that DES, especially those
      releasing sirolimus from a polymer (SES) or those releasing paclitaxel from a
      polymer (PES), significantly and relevantly reduce the restenosis rate and hence
      the number of needed reinterventions in the target vessel (target vessel
      revascularization [TVR]) as compared to bare metal stents (BMS). For this
      improvement of quality of life, cost-effectiveness analyses comparing DES and BMS
      in the US and German health care systems have been reported. For the comparison
      of DES and coronary artery bypass graft surgery (CABG), no economic data
      regarding the German health care system have been published. The goal of the
      present study is to provide such an economic analysis investigating the question
      whether DES can reduce costs as compared to CABG within the German health care
      system. METHODS: Based on the clinical data for PCI with a PES for long and
      complex lesions (TAXUS VI) and for CABG (ARTS I), the comparison was calculated
      for the time interval of 1 year. The analysis of the PCI group was derived from a
      TVR of 11% including a CABG rate of 1%; the CABG group analysis was based on a
      TVR of 3.8% including a PCI rate of 3.1% and a re-CABG rate of 0.7%. At a stent
      factor of 2.75, the costs per stent were calculated to be 250 Euro for the BMS
      and 1,500 Euro for the PES. The total costs for 12 months included the follow-up
      costs for reinterventions. The results were tested for stability according to a
      sensitivity analysis. RESULTS: Patients' demographics were well comparable
      between the PCI and the CABG groups. The primary costs, including the
      reinterventions, were 7,841 Euro for PCI and 12,415 Euro for CABG. The
      sensitivity analysis revealed that only at more than eight stents per patient and
      a need for reintervention of ca. 10% did the cost of PCI with PES reach the level
      of the cost for CABG. CONCLUSION: Within the German health care system, in
      patients with a social insurance, PCI of long and complex lesions with PES
      significantly reduces costs as compared to CABG to the amount of 4,574 Euro per
      patient. The cost-effectiveness analyses of currently ongoing prospective,
      randomized trials (SYNTAX und FREEDOM) will provide more insight into the
      economic comparison of PCI with DES and CABG.

PMID- 15965812
TI  - Biventricular and biatrial thrombi in a patient with heparin-induced
      thrombocytopenia after coronary artery bypass grafting.

PMID- 15965813
TI  - [Child and adolescent rheumatology].

PMID- 15965814
TI  - [Acute rheumatic fever (ARF) and poststreptococcal reactive arthritis (PSRA)--an
      update].
AB  - Betahemolytic strains of streptococcus A are able to induce a spectrum of
      immunologically induced diseases, depending on the immunogenic M structure of the
      bacteria as well as on the genetic determined reaction of the host. In acute
      rheumatic fever (ARF) the Jones criteria, revised and modified several times and
      updated in 1992, remain the diagnostic standard. Echocardiography, still not
      included in the Jones criteria, has become a very important diagnostic tool,
      especially as half of the ARF induced carditis cases are clinically inapparent.
      Diagnosis may be very difficult if arthritis is the only major sign, especially
      if not occurring in the typical migrating pattern, a fact frequently reported
      from countries with a high risk of ARF. Poststreptococcal reactive arthritis
      (PSRA) has been described as a different entity as well as a part of rheumatic
      fever. There is a lack of validated diagnostic criteria to establish a reliable
      diagnosis. There are no accepted recommendations for antibiotic prophylaxis in
      PSRA.

PMID- 15965815
TI  - [The treatment of juvenile rheumatism: pharmacotherapy].
AB  - The treatment of juvenile idiopathic arthritis has changed a great deal in the
      last few years. Pharmacomedical treatment, physiotherapy and teaching the
      patients and parents are the mainstays of successful therapy. Using all available
      treatment options and thanks to new therapeutic options (TNFalpha-blockade) and
      due to a better understanding of the pathogenesis, individual therapeutic
      strategies provide adequate disease control in the large majority of cases.
      According to the subtype of juvenile idiopathic arthritis, different medications
      are used in combination with nonsteroidal antiinflammatory drugs (NSAID) which
      are used initially. Methotrexate (MTX) and steroids in various applications are
      the drugs of choice for the systemic and polyarticular courses; intraarticular
      steroids, sulfasalazine and hydroxychloroquine for the oligoarticular subtype.
      The new option of TNFalpha-blockade (Etanercept, Infliximab, Adalimumab) offers
      significant clinical benefit in patients with polyarticular involvement, who do
      not respond to MTX. Further biological agents (Anakinra, Abatacept, Atlizumab)
      are used in children and adolescents in clinical studies. Rarely azathioprine,
      cyclosporine A, leflunomide and cyclophosphamide are used. Stem cell
      transplantation has been tried as a very last resort but interpretation of the
      results is controversial. Due to the improvement of the therapeutic options, the
      approaches to the patients and their disease has changed and cautious optimism is
      justified.

PMID- 15965816
TI  - [Importance of the new biologicals and cytokine antagonists in the treatment of
      juvenile idiopathic arthritis (JIA)].
AB  - Juvenile idiopathic arthritis is group of diseases of unknown aetiology
      characterised by the occurrence of chronic arthritis during childhood. Compared
      to adult onset rheumatoid arthritis, its course is more variable. Increasing
      knowledge of the inflammatory process as well as in molecular genetics and
      biotechnology has enable the production of new drugs, the biologicals. These are
      able to specifically block mechanisms of immune activation and thereby interfere
      with the inflammatory process. An increasing number of biologicals have been
      tried in clinical studies in adults suffering from rheumatoid arthritis,
      psoriasis or psoriasis arthritis and a couple of them were already licensed for
      treatment. Treatment of juvenile idiopathic arthritis by blockade of
      tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the
      monoclonal antibodies Infliximab and Adalimumab showed comparable clinical
      efficacy. Blockade of TNF therefore already reached a certain place in the
      therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently,
      only Etanercept is licensed for treatment of active juvenile polyarthritis
      refractory to methotrexate. Studies using Infliximab and Adalimumab will be
      completed in the near future. However, antibodies blocking TNF may already be
      used in patients suffering from active uncontrolled chronic uveitis in whom
      visual impairment is threatening. TNF blockers may also be indicated in juvenile
      ankylosing spondylitis. The use of further biologicals, the interleukin-1
      receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for
      interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell
      membrane molecule CD28, remain experimental and should be preserved for clinical
      studies.

PMID- 15965817
TI  - [Transition clinic--it is not always a simple segue in rheumatology for adults].
AB  - Chronic inflammatory rheumatic diseases with onset in childhood often persist
      into adulthood and result in a considerable number of patients in impairments of
      body functions and structures, activities at the individual level and
      participation in society. Continuation of health care beyond adolescence is,
      therefore, necessary. Its provision should be of high quality, coordinated,
      uninterrupted, patient-centred and developmentally appropriate to ensure smooth
      transitions between children's and adult services and positive outcomes of
      transition for the young people themselves. Existing research is very persuasive
      on the need to improve transitions for young people with rheumatic diseases. To
      achieve effective transition, not only disease specific, but also aspects of
      growth and development have to be taken into account. Paediatric and adult
      rheumatologists should establish close cooperation and implement specific
      transition programs to meet the special health care needs of these patients.

PMID- 15965818
TI  - [Synovialitis score: histopathological grading system for chronic rheumatic and
      non-rheumatic synovialitis].
AB  - Standardization of the histopathological assessment of synovial membrane
      specimens might facilitate the diagnosis of chronic rheumatic and non-rheumatic
      joint diseases. We would like to propose a histological graduation scheme
      ("synovialitis score"), which is applicable to all forms of synovitis,
      irrespective of its etiology. This score evaluates the three compartments of
      chronic synovialitis [enlargement of lining cell layer, activation of synovial
      stroma (i. e. resident cells), leukocytic infiltrate] semiquantitatively (from
      0=absent to 3=strong). Each compartment is graded separately, and the sum
      resembles the synovialitis score, which is interpreted as follows: 0-1: no
      synovialitis, 2- 3: slight synovialitis, 4-6: moderate synovialitis, 7-9: strong
      synovialitis (for sample photos see also
      www.charite.de/ch/patho/Webpage/pages/forschung/arbeitsgruppen/ag
      krenn/index.htm). A total of 483 synovial specimens (resections n=462, biopsies
      n=21) were graded by two independent observers. Clinical diagnoses were
      osteoarthrosis (OA; n=153), posttraumatic arthritis (PtA; n=31), rheumatoid
      arthritis (RA; n=239), psoriatic arthritis (PsA; n=32), reactive arthritis (ReA;
      n=7), and controls (Co, n=21) from necropsies of patients without joint damage.
      The correlation between two observers was high (p<0.001). The correlation
      coefficient between the different samples from the same joint in n=112 cases was
      between 0.86 and 0.95. Median synovialitis scores when correlated with clinical
      diagnoses were: Co 0.5, OA 2, PtA 3, PsA 3, ReA 4, RA 5. The differences in
      scores between Co and all other groups were highly significant (p<0.001). A
      synovialitis score of 4 points and more was strongly associated with rheumatic
      joint diseases (sensitivity 73%, specificity 86%). Validation of the synovialitis
      score by gene expression data showed good correlations for the lining cell
      enlargement with MMP1 (0.685), for the leukocytic infiltrate with CD3 (0.754) and
      CD138 (0.744) and for the stroma activation with CD14 (0.744). The proposed
      synovialitis score is based on well definable histopathologic criteria and
      contributes to the diagnosis of rheumatic and non-rheumatic joint diseases.

PMID- 15965819
TI  - [Jaccoud arthritis in systemic lupus erythematosus].
AB  - Jaccoud arthritis is a manifestation of systemic lupus erythematosus and other
      rheumatic diseases. It is characterized by non-erosive subluxation and
      synovialitis ultimately leading to severe deformity of the hands. The clinical
      aspect may be misleading and suggestive of rheumatoid arthritis manifestations.

PMID- 15965820
TI  - [Routine report on the medical rehabilitation of patients with musculoskeletal
      diseases].
AB  - The commission "Rehabilitation" of the German Society of Rheumatology compiled a
      data set for a routine report of the rehabilitation system for muskuloskeletal
      diseases. More than 250 rehabilitation hospitals offer inpatient rehabilitation
      for patients with musculoskeletal diseases. The prevalence of inpatient
      rehabilitation decreased due to new legislative rules in 1997, increased again
      thereafter but has not reached the former level. The prevalence of inpatient
      rehabilitation during the preceding year in patients with inflammatory rheumatic
      diseases treated by rheumatologists amounts to 12% with higher figures in men
      than in women and lower figures in the area of the former German Democratic
      Republic. The prevalence of outpatient rehabilitation increased during the last
      few years but, currently, does not exceed 5% of the entire rehabilitation
      procedures.

PMID- 15965821
TI  - [Guidelines in rheumatology--how far along are we].

PMID- 15965822
TI  - [Reducing toxicity of methotrexate with folic acid].
AB  - BACKGROUND: Methotrexate is considered to have the best ratio of efficacy to
      toxicity of the disease modifying antirheumatic drugs. Recently it has been shown
      to enhance the life expectancy of patients with rheumatoid arthritis. Some 30-60%
      of RA patients discontinue MTX treatment within 1 year because of side-effects.
      In this review, the current data about supplementation with folate or folinic
      acid and their effect on the toxicity and efficacy of low-dose methotrexate
      therapy are analysed. METHODS: A Medline search was performed using "folate",
      "folic acid", "folinic acid", "homocysteine", "methotrexate", "cardiovascular",
      "heart infarction" and "rheumatoid arthritis" as search terms. The relevant
      literature was reviewed and other papers referred to as references were explored.
      CONCLUSION: Both folate and folinic acid reduce methotrexate toxicity and the
      discontinuation rate, and decrease methotrexate-induced hyperhomocysteinemia.
      Folate is less expensive, more secure and easier to handle than folinic acid. The
      efficacy of methotrexate probably decreases slightly, but the benefit outweighs
      the risk. Folate supplementation should, therefore, be routinely prescribed to
      every patient taking low-dose methotrexate.

PMID- 15965823
TI  - [Obituary of Prof. Dr. med. Walter Mohing].

PMID- 15965826
TI  - Prosthetic joint infections: update in diagnosis and treatment.
AB  - The pathogenesis of prosthetic joint infection is related to microorganisms
      growing in biofilms, rendering these infections difficult to diagnose and to
      eradicate. Low-grade infections in particular are difficult to distinguish from
      aseptic failure, often presenting only with early loosening and persisting pain,
      or no clinical signs of infection at all. A combination of preoperative and
      intraoperative tests is usually needed for an accurate diagnosis of infection of
      prosthetic joint infections. Successful treatment requires adequate surgical
      procedure combined with long-term antimicrobial therapy, ideally with an agent
      acting on adhering stationary- phase microorganisms. In this article,
      epidemiology, pathogenesis, diagnosis and treatment of prosthetic joint
      infections are reviewed.

PMID- 15965827
TI  - Reliability of varicella history in children and adolescents.
AB  - QUESTION UNDER STUDY: Only limited data are available regarding the reliability
      of the varicella zoster virus (VZV) history in children and adolescents. Our goal
      was to determine positive and negative predictive values of varicella history in
      a prospective cross-sectional study. METHODS: Patients 1-18 years of age who were
      hospitalised in our institution between 1999 and 2000 were eligible for
      participation when a blood specimen was taken for any medical reason. Patients
      with current varicella, immunodeficiency, immunoglobulin treatment in the
      previous 6 months, or significant language barriers were excluded. After informed
      consent had been obtained, parents were asked whether their child had a history
      of varicella (categorized as definite, probable, possible, negative or unknown).
      Anti-VZV-IgG antibodies were then tested by ELISA (Enzygnost). If the ELISA
      result was indeterminate, the specimen was analysed by fluorescent-antibody
      staining of membrane antigen in VZV-infected cells (FAMA), the serological gold
      standard. RESULTS: 449 patients (mean age 6.4 years, median 5.4 years) were
      enrolled. History of varicella was definite in 234 (52%), probable in 12 (3%),
      possible in 1, negative in 196 (44%) and unknown in 6 (1%) patients. Overall, 61%
      (95% CI: 56-65) of patients were positive for VZV antibodies. Seroprevalence was
      25%, 68% and 95% in 1-4 year olds (group 1, n = 167), 5-8 year olds (group 2, n =
      136) and 9-18 year olds (group 3, n = 146), respectively. The positive predictive
      value of a definite history of varicella was 98% (95% CI: 96-100) (93%, 100%, and
      98% in groups 1, 2 and 3, respectively). The negative predictive value was 85%
      (95% CI: 80-90), decreasing with age (group 1: 97%; group 2: 77%; group 3: 26%).
      CONCLUSIONS: The positive predictive value of a history of varicella is high in
      children and adolescents. In countries where universal immunization against
      varicella is not recommended, selectively immunizing adolescents with a negative
      history can reduce the rate of susceptible individuals efficiently.

PMID- 15965828
TI  - Perception of the damaging effects of smoking, and brief cessation counselling by
      doctors.
AB  - An open prospective study was conducted among the patients visiting an urban
      medical policlinic for the first time without an appointment to assess whether
      the immigrants (who represent more than half of our patients) are aware of the
      health effects of smoking, whether the level of acculturation influences
      knowledge, and whether doctors give similar advice to Swiss and foreign smokers.
      226 smokers, 105 Swiss (46.5%), and 121 foreign-born (53.5%), participated in the
      study. 32.2% (95% CI [24.4%; 41.1%]) of migrants and 9.6% [5.3%; 16.8%] of Swiss
      patients were not aware of negative effects of smoking. After adjustment for age,
      the multivariate model showed that the estimated odds of "ignorance of health
      effects of smoking" was higher for people lacking mastery of the local language
      compared with those mastering it (odds ratio (OR) = 7.5 [3.6; 15.8], p < 0.001),
      and higher for men (OR = 4.3 [1.9; 10.0], p < 0.001). Advice to stop smoking was
      given with similar frequency to immigrants (31.9% [24.2%; 40.8%] and Swiss
      patients (29.0% [21.0%; 38.5%]). Nonintegrated patients did not appear to receive
      less counselling than integrated patients (OR = 1.1 [0.6; 2.1], p = 0.812). We
      conclude that the level of knowledge among male immigrants not integrated or
      unable to speak the local language is lower than among integrated foreign-born
      and Swiss patients. Smoking cessation counselling by a doctor was only given to a
      minority of patients, but such counselling seemed irrespective of nationality.

PMID- 15965830
TI  - Therapeutic potential of synthetic CpG DNA--current status and future directions.

PMID- 15965829
TI  - Epstein-Barr virus DNA in serum in a HIV-infected patient during development and
      treatment of non-Hodgkin's lymphoma.
AB  - Immunocompromised patients are at risk of developing Epstein-Barr virus (EBV)
      related lymphoproliferative disorders. Quantitative determination of serum EBV
      DNA permits early diagnosis of an AIDS-related non-Hodgkin's lymphoma, and
      surveillance of treatment response and/or relapse, and thus may be a useful tool
      to monitor disease activity.

PMID- 15965831
TI  - American Diabetes Association--61st scientific sessions.

PMID- 15965832
TI  - American Diabetes Association--61st scientific sessions. Poster presentations:
      integrative physiology.

PMID- 15965833
TI  - American Diabetes Association--61st scientific sessions. Poster presentations:
      therapeutics and islet biology.

PMID- 15965834
TI  - American Diabetes Association--61st scientific sessions. Clinical trials and new
      drug programs.

PMID- 15965835
TI  - American Diabetes Association--61st scientific sessions. GLP-1, exendin and PPAR
      modulators.

PMID- 15965836
TI  - World Chemistry Congress.

PMID- 15965837
TI  - World Chemistry Congress. Challenges for drug discovery and development in the
      21st century.

PMID- 15965838
TI  - International Society on Thrombosis and Haemostasis--XVIIIth congress. Oral
      presentations.

PMID- 15965839
TI  - International Society on Thrombosis and Haemostasis--XVIIIth congress. Poster
      presentations.

PMID- 15965840
TI  - International Society on Thrombosis and Haemostasis--XVIIIth congress. Managing
      thromboembolic disease in adults and children.

PMID- 15965841
TI  - Severe asthma and COPD--the good, the bad and the ugly.

PMID- 15965842
TI  - Royal Society of Chemistry--sixth international symposium on applied bioinorganic
      chemistry.
AB  - This was the sixth in a series of symposia that began in Beijing, China in 1986.
      Approximately 100 chemists, environmental and biomedical scientists from 25
      countries attended the meeting and presented some 80 papers on topics ranging
      from cancer chemotherapy to the production of paper. About half the papers
      presented could be broadly described as having medical implications, and of
      these, approximately half related directly to the use of platinum and the
      potential uses of other metals, such as palladium and the lanthanides, as
      anticancer agents. Many of these papers provided valuable insights into
      mechanisms of action and offered pointers for future research, but only rarely
      did they point to potential new drugs that might find early exploitation in
      clinical medicine. Two of the more exciting clinical developments were the
      introduction of the insulin-mimetic bis(maltolato)oxovanadium(IV) (KP-102;
      Kinetek Pharmaceuticals Inc/University of British Columbia) into clinical trials
      in the UK for the treatment of Type II diabetes, and the increasing importance of
      the orally active agent 3-hydroxy-pyridin-4-one-deferiprone (Apotex Inc/Cipla
      Ltd), in the treatment of iron overload in thalassemia.

PMID- 15965843
TI  - Controlled release of bioactive materials--28th international symposium.

PMID- 15965844
TI  - Controlled release of bioactive materials--28th international symposium. Tissue
      barriers and protein delivery.

PMID- 15965845
TI  - Controlled release of bioactive materials--28th international symposium.
      Carbohydrate drug carriers: cyclodextrins and chitosans.

PMID- 15965846
TI  - Advanced methods of pharmacokinetic and pharmacodynamic systems analysis.
AB  - The Ninth Workshop on Advanced Methods of Pharmacokinetic and Pharmacodynamic
      Systems Analysis was held at the Biomedical Simulations Resource Center at the
      University of Southern California. The speakers and attendees included a number
      of eminent researchers in the field of modeling and simulation in drug
      development. Although many of the talks were on data either previously published
      or presented at other meetings, it is apparent that the field as a whole is
      advancing with significant progress being made on directing and influencing the
      drug development process.

PMID- 15965847
TI  - Chronic lung diseases--Institut Pasteur Euroconference.

PMID- 15965848
TI  - Innovative technologies--molecules and processes. The BACS conference at ChemSpec
      Europe 2001.

PMID- 15965849
TI  - Boosting your product pipeline through innovative licensing. Pinpointing and
      managing successful alliances to remain competitive.
AB  - With the recent outbreak of large mergers and acquisitions and the looming
      pipeline crisis among large pharmaceutical companies, this meeting aimed to bring
      together senior officers from the business development and licensing sectors of
      top biotech and pharma companies, to discuss all aspects of licensing with a
      focus on remaining competitive. Along with in-depth analyses and theories
      delivered by representatives from investment banks, consultancy firms and
      academia, the conference presented delegates with interesting viewpoints and
      practical advice on partnering strategies, and issues surrounding licensing.

PMID- 15965850
TI  - Where are the new therapies for anxiety and obsessive-compulsive disorders?
AB  - The benzodiazepines have monopolized the acute anxiety market for about 40 years,
      but their potential for tolerance and dependency has stimulated an interest in
      alternative anxiolytics. Until recently, however, attention has focused on
      existing drugs such as monoamine oxidase inhibitors, tricyclic antidepressants,
      selective serotonin reuptake inhibitors. The 5-HT1A partial agonist, buspirone
      (Bristol-Myers-Squibb), is one of the few compounds developed principally as an
      anxiolytic since the benzodiazepines. The challenge for the future is not only to
      find efficacious treatments with a rapid onset of action and an acceptable side
      effect profile but also to determine the optimal compounds for each of the
      different anxiety disorders.

PMID- 15965851
TI  - Cardiovascular combination therapy.

PMID- 15965852
TI  - Semaxanib (SUGEN).
AB  - SUGEN (owned by Pharmacia) is developing semaxanib (SU-5416), the lead in a
      series of small molecule inhibitors of the flk-1 tyrosine kinase receptor (flk-1
      RTK), for the potential treatment of solid tumors (via suppression of metastasis
      and angiogenesis) [191353], [264484]. In July 1999, phase III trials for
      colorectal and lung cancer were initiated [326969]. In March 2001, phase III
      trials were initiated for the compound as an addition to a standard chemotherapy
      regimen in colorectal cancer [402241]; at this time, Pharmacia, as well as the
      NCI, was conducting clinical studies for numerous other solid and hematological
      cancers [402241]. By October 2000, oral forms of the compound were also being
      evaluated [385699]. In July 2000, Pharmacia anticipated US and international
      filing in 2001 [374505]. Taiho and SUGEN have agreed a joint development program
      for SUGEN's angiogenesis inhibitors [293021]. In August 1998, the USPTO issued US
      05792783 to SUGEN, covering a family of compounds, including semaxanib. The
      patent claims cover the compounds and composition, as well as methods of use in a
      variety of diseases, including cancer [294467]. In August 1998, the USPTO issued
      US-05792783 to SUGEN, covering a family of compounds, including semaxanib. The
      patent claims cover the compounds and composition, as well as methods of use in a
      variety of diseases, including cancer [294467].

PMID- 15965853
TI  - PRO-140 (Progenics).
AB  - PRO-140, a monoclonal antibody against the HIV coreceptor CCR5, is under
      investigation by Progenics and the Aaron Diamond AIDS Research Center (ADARC) as
      a potential treatment for HIV infection [211441], [286246], [286247]. Phase I/II
      trials were expected to commence during 2001 [395621], [409142], despite being
      initially planned for 2000 [322637], [361819], [365216], [375598], [408483]. In
      January 1998, ADARC and Progenics reported that the HIV binding site on the CCR5
      coreceptor is distinct from betachemokine binding domains, which they claimed may
      allow for the development of therapeutics with fewer side effects [273391],
      421256]. In vitro studies have shown PRO-140 potently blocked all of 17 primary
      HIV isolates that use CCR5 as a fusion coreceptor [342173]. In October 2000,
      Progenics was awarded an SBIR grant to fund a 2-year project exploring the
      breadth, potency and durability of PRO-140 therapy in laboratory and animal
      models of HIV infection. This project was a collaboration between Progenics,
      Weill Medical College of Cornell University and the Scripps Research Institute
      [385982]. In May 1999, the company entered into an agreement with Protein Design
      Labs (PDL) for the humanization by PDL of PRO-140 [325445]. In November 1997,
      Progenics was awarded a 600,000 dollars grant from the NIAID for the examination
      of new approaches to HIV vaccine design based on CCR5 [268407].

PMID- 15965855
TI  - [Clinical progress].

PMID- 15965856
TI  - [Neurology--current treatment concepts].

PMID- 15965857
TI  - [Cardiology -- what is new?].

PMID- 15965858
TI  - [Pneumology -- from phthisiology to regenerative medicine].

PMID- 15965859
TI  - [Gastroenterology/hepatology--light and darkness in the digestive tract. Effects
      of technology, genetics and biology].

PMID- 15965860
TI  - [Nephrology -- familiar knowledge in the light of new discoveries in molecular
      and cell biology].

PMID- 15965861
TI  - [Rheumatology--searching for the individual therapeutic cocktail].

PMID- 15965862
TI  - [Infectiology -- new scenarios, ever increasing tasks].

PMID- 15965863
TI  - [Immunology--risk management in the body].

PMID- 15965864
TI  - [Oncological surgery -- surgical oncology].

PMID- 15965865
TI  - [Molecular medicine--personalized medicine. Principles and state-of-the-art].

PMID- 15965866
TI  - [Hormones and metabolism -- exciting paths from biology to clinics].

PMID- 15965867
TI  - [Health services research -- physicians' competence].

PMID- 15965868
TI  - [Cruro-pedal reconstructions -- what is evidence-based?].

PMID- 15965869
TI  - [The visceral ischemia syndrome].

PMID- 15965870
TI  - [Intensive care medicine -- update 2004].
AB  - This manuscript gives a review about important studies addressing problems in
      intensive care medicine that have been published in journals focussing on
      critical care medicine and surgery in 2004. Only clinical studies are included in
      this review, mostly metaanalyses, randomized controlled trials and a few
      important or interesting observational studies. In addition to describing major
      results a critical appraisal of each study is undertaken, which, however, is
      neither comprehensive nor complete. It is merely intentioned to address some
      important aspects for the reader that should be accounted for while interpreting
      the results. It is important to note that among the large number of excellent
      studies there is a substantial proportion of trials with negative results that
      significantly add to our knowledge. Some of the topics addressed in this
      manuscript include vasopressin as an alternative to epinephrine during
      cardiopulmonary resuscitation, a specification concerning the use of activated
      protein C in patients with sepsis, the role of steroids in the treatment of
      sepsis and traumatic brain injury, the epidemiology of ALI and ARDS, the role of
      sedation protocols, weaning protocols and the timing of tracheostomy for the
      duration of mechanical ventilation, the potential benefit of catheters with
      antimicrobial coating to reduce catheter-related sepsis, and the benefit of
      enteral nutrition as compared to the parenteral application.

PMID- 15965871
TI  - [Injury to visceral organs by ischemia and reperfusion. Processes in pathogenetic
      networks].
AB  - The injury of the visceral organs liver, stomach/intestine and pancreas by
      ischemia and reperfusion can be understood as a process, the events of which
      represent junctions in pathogenetic networks. In the phase of ischemia, damage of
      cells by oxygen deficiency is the center of the injurious process. The initial
      event is the decreased mitochondrial energy supply. Changes in ion homeostasis,
      activation of hydrolases as well as formation of large pores in the mitochondrial
      membranes, the so-called mitochondrial permeability transition, are other
      decisive events in the network of the hypoxic cell injury. Cell damage in the
      phase of reperfusion is either a consequence of changes in the cells, originating
      from the phase of ischemia, or the result of an inflammatory tissue reaction. In
      both cases reactive oxygen species are important triggers of the cell damage.
      Disturbances of the glutathione equilibrium and of the calcium balance as well as
      again the mitochondrial permeability transition and the activation of hydrolases
      belong to the events in the network of cell injury in this phase. Even more than
      the intracellular events of the cell damage, the events of the inflammatory
      tissue reaction are linked net-like with one another. Initiated by cells already
      damaged, an increased release of reactive oxygen species, nitrogen monoxide and
      other mediators, activation of macrophages, neutrophils, endothelial cells,
      lymphocytes and the complement system as well as disturbances of the
      microcirculation form a network of interacting events, which leads to a
      perpetuation of the tissue damage. A multiplicity of injurious pathways can be
      designed due to the net-like linkage of the events of the cell and tissue damage.
      An important consequence, which results from the construct of the pathogenetic
      networks, is therefore the demand that an effective therapy of the ischemia
      reperfusion injury of visceral organs can be attained only by blockade of several
      central junctions.

PMID- 15965872
TI  - [Acute and chronic progressive abdominal pain: what is the role of radiogical
      imaging?].
AB  - There are many causes for acute or chronic progressive abdominal pain. Although
      only about one percent of these patients suffer from acute mesenteric ischemia
      (MI), an efficient diagnostic work-up is mandatory to reduce the high mortality.
      An overview about the possibilities of conventional and modern imaging modalities
      is given. Plain films and ultrasonography are still important in the basic work
      up, however, its sensitivity is limited. Angiography has a high sensitivity and
      specitivity. However, angiography is not always available. Modern spiral-CT is
      widely available and its sensitivity is already similar to angiography. An other
      advantage of CT is the possibility to detect the most other frequent causes of
      abdominal pain. Therefore CT should be performed as fast as possible.

PMID- 15965874
TI  - [Recognizing acute mesenteric ischaemia too late: reasons and diagnostic approach
      from a surgical point of view].
AB  - Survival of patients with acute mesenteric ischaemia is decisively dependent upon
      early diagnosis and non-delayed treatment. Maximum shortening of the admission-to
      treatment-time is the main task, as the prehospital phase (e. g. symptom-to
      admission-interval) varies considerably and is hardly to be influenced. "Acute
      mesenteric ischaemia" should early be considered as a possible diagnosis in
      patients presenting with abdominal symptoms of unknown cause bearing risk-factors
      for intestinal ischaemic disorders. In such cases an immediate angiography is the
      method of choice to confirm the diagnosis. To avoid irreversible intestinal
      damage, immediate laparotomy is induced if competent conducted angiography is not
      available within one hour after suspicion of intestinal ischaemia.

PMID- 15965873
TI  - [Influence of cardiac circulation and medication on the perfusion of the
      intestine].
AB  - Perfusion of the abdomen is determined by cardiac function and circulation.
      Intestinal ischemia can be caused by Non occlusive bowel ischemia (NOD) that is
      important in internal as well as surgical intensive care medicine. Cardiac
      medication can influence perfusion of the bowel: 1) digitalis increases muscular
      tonus and decreases perfusion regulation b) diuretics lead to hypovolemia,
      hypotonia and malperfusion, c) antihypertensive medication can cause
      intraoperative hypotension that demands catecholamines, d) catecholamines can
      reduce perfusion by pathologic vasoconstriction in the splanchnicus area.
      Preoperative medication should respect 1) preoperatively taken ACE-inhibitors
      should be given postoperatively, as they have protective influence on the
      microcirculation of the bowel, 2) beta-blockers stabilize the myogenic tonus of
      the abdominal vessels, reduce an overshot of the parasympatheticus and diminish
      the risk of neurogenic abdominal shock, 3) catecholamines should be used with
      respect to ischemia of the bowel. Therapy of NOD should be focused on the primary
      vascular and hemodynamic causes and also take care for bacterial translocation
      and consecutive sepsis.

PMID- 15965875
TI  - [Celiac trunk compression: angiographic phenomenon or cause of ischemic abdominal
      complaints?].
AB  - Compression of the celiac trunk commonly occurs in young men and women as well.
      Most of the patients suffering from this rare disease derive from a large pool of
      people having diffuse and chronic abdominal complaints including epigastric pain,
      postprandial abdominal pain and diarrhea leading to weight loss. Aim of the study
      was the finding of true criteria which can guarantee a successful operative
      procedure. A major issue in preoperative assessment is color flow Duplex imaging
      of the celiac axis. The most important finding aside from clinical symptoms is a
      peak flow in the celiac axis of more than 200 cm/s during inspiration and
      expiration position of the diaphragm. In addition arteriography of the celiac
      axis and superior mesenteric artery (SMA) showing a steal phenomenon is
      essential. Because of the rareness of the disease "only" 15 patients were
      operated on including intraoperative balloon dilatation of the celiac trunk. 93 %
      had a long term follow up success. Normal values of peak flow velocity in the
      mesenteric arteries were determined in more than one hundred healthy persons and
      compared to findings in the literature which were nearly identical. As a result
      of the study it could be shown that a successful outcome of the operative
      procedure can be expected when certain essential criteria are observed: 1. peak
      flow velocity in the celiac trunk higher than 200 cm/s during in- and expiration
      2. steal effect via pancreatic arcades from the superior mesenteric artery
      documented by Duplex ultrasound and arteriography 3. triad of symptoms:
      epigastric pain, postprandial pain and weight loss of more than 5 kg. Special
      emphasis is given to the possible occurrence of severe complications after liver
      transplantations and pancreatic surgery, if the diagnosis "median arcuate
      ligament compression" is not known.

PMID- 15965876
TI  - Antegrade revascularisation for chronic visceral ischaemia.
AB  - There is no consensus of opinion on the best surgical approach for the management
      of chronic visceral ischaemia. The antegrade revascularisation has several
      advantages. It provides an excellent exposure of the supraceliac aorta, the
      option of originating the bypass from several areas of the distal thoracic and
      supraceliac aorta that is usually spared of atherosclerosis and the bypass is
      placed in the direction of normal blood flow (antegrade direction). The
      supraceliac aorta can be approached through an abdominal or a low
      thoracoabdominal extraperitoneal route. The results on several series indicate
      that it is a durable and effective technique.

PMID- 15965877
TI  - [Surgical treatment of portal hypertension].
AB  - A switch to decompressive shunt procedures is mandatory if endoscopic therapy
      fails to control recurrent variceal hemorrhage. Surgical shunt procedures
      continue to be safe, highly effective and durable procedures to control variceal
      bleeding in patients with low operative risk and good liver function (Child A).
      In cirrhotics, elective operations using portal flow preserving techniques such
      as a selective distal splenorenal shunt (Warren) or a partial portocaval small
      diameter interposition shunt (Sarfeh) should be preferred. Rarely, end-to-side
      portocaval shunt may serve as a salvage procedure if emergent endoscopic
      treatment or TIPS insertion fail to stop bleeding. Until definitive results from
      randomized trials are available patients with good prognosis (Child-Pugh A and B)
      can be regarded as candidates for surgical shunts. For patients with noncirrhotic
      portal hypertension, in particular with extrahepatic portal vein thrombosis,
      portosystemic shunt surgery represents the only effective therapy which leads to
      freedom of recurrent bleeding and repeated endoscopies for many years, and
      improves hypersplenism without deteriorating liver function or encephalopathy.
      Gastroesophageal devascularization and other direct variceal ablative procedures
      should be restricted to treat endoscopic therapy failures without shuntable
      portal tributaries.

PMID- 15965878
TI  - [Transjugular intrahepatic portosystemic stent shunt: indications and long-term
      outcome].
AB  - The transjugular intrahepatic portosystemic stent shunt has replaced surgical
      shunt procedures as the standard therapy for complications of portal hypertension
      such as refractory ascites and recurrent variceal bleeding. However,
      reinterventions due to TIPS stenosis are necessary in 25-50 %. Major
      complications are the manifestation or worsening of hepatic encephalopathy.
      Recent studies using PTFE covered stents have shown lower stenosis rates and a
      trend towards prolonged survival.

PMID- 15965879
TI  - [Vena cava filter -- is there an indication for implantation?].
AB  - The indication of vena cava filter implantation is controversially discussed. On
      the basis of the available literature and our own results a critical analysis of
      this issue is given. Between 1994 and 2003, we inserted a total of 29 vena cava
      filters; 24 temporary and 5 permanent filters. In twelve patients, the placement
      of the filter was indicated due to pulmonary embolism and a contra-indication to
      dose adjusted heparin therapy. Seven additional patients experienced a recurrent
      pulmonary embolism despite adequate heparin therapy. An additional prophylactic
      filter insertion was carried out in ten patients. The temporary vena cava filters
      were left in place between 7 to 38 days with an average of 17 days. Total
      implantation time of temporary filters was scheduled until complete mobilisation
      of the patients, generally in conjunction with an effective dosage of oral
      anticoagulants. No patient died in connection with the insertion of the filter
      and no further pulmonary embolisms occurred. One case of inferior vena cava
      thrombosis occurred in each group of temporary and permanent filters. In one
      third of the removed filter systems, thrombi in the filter were found. Local
      infections of the catheter and introducer sets were observed in two patients.
      Moreover, in one case the strut of a temporary filter broke and subsequently
      dislocated 17 days after insertion. However, there is little evidence concerning
      vena cava filters, and further investigations are necessary. Until additional
      data are available, filters should generally be restricted to patients with deep
      venous thrombosis and pulmonary embolism who cannot receive anticoagulation, and
      highly selected cases.

PMID- 15965880
TI  - [Laparoscopic incisional hernia repair -- an alternative to the conventional
      procedure?].
AB  - INTRODUCTION: Tension-free incisional hernia repair using alloplastic material
      increasingly replaces conventional repair techniques. The aim of the present
      study was to evaluate the early and long-term complications as well as patients'
      satisfaction. METHODS: Laparoscopic hernia repair with intraperitoneal mesh
      implantation (PTFE) was performed on 28 patients at the Klinikum Grosshadern
      between 2000 and 2003 (16 males, 12 females, average age 61.2). Intra- and
      postoperative complications were registered retrospectively. In addition, 25
      patients were evaluated for recurrence, postoperative pain and patient
      contentment (median follow-up 383 days). RESULTS: A low complication rate was
      observed in our patient collective. One trocar bleeding occurred. 2 patients
      presented with wound hematoma. The recurrence rate was 8 % (2/25). 60 % of the
      patients were free of pain postoperatively. 88 % would once again choose the
      laparoscopic approach for incisional hernia repair. DISCUSSION: The laparoscopic
      technique was associated with a low recurrence rate, a small rate of wound
      infections and high patient comfort. Thus, the laparoscopic approach for mesh
      implantation appears to be a safe and effective method for the treatment of
      incisional hernias. The efficiency of laparoscopic intraperitoneal mesh
      implantation, however, should be evaluated within a prospectively randomized
      multicenter trial.

PMID- 15965881
TI  - [Laparoscopic hernioplasty by total extraperitoneal approach].
AB  - INTRODUCTION: Despite the increasing acceptance of the TEP-procedure by patients
      and general practitioners this method has to be further examined. In addition to
      the classic surgical criteria of examination, subjective aspects of patient
      comfort must be taken into consideration as they are getting more and more
      significant for the evaluation of different methods. METHODS: According to this
      targets patients were clinically examined and questioned about specific topics
      regarding their quality of life after TEP-surgery and evaluated prospectively.
      RESULTS: Between 1995 and 2000 endoscopic total extraperitoneal hernioplasty
      (TEP) was used for 200 inguinal hernia repairs in 195 patients. 195 patients
      could be interviewed about the operation's outcome and examined physically and
      sonographically after 3 months, 188 patients after 6 months and 184 patients
      after 12 months post-op. The recurrence rate was 1.7 %, the rate of major
      complications was < 1 %. Sensitivity disorders were found in 7.3 % of all cases
      at the final examination prior to discharging but none at the 3 months check-up.
      The median postoperative period until the resumption of sexual intimacy was
      approximately two weeks, but one male patient reported about long-lasting pain in
      copulation (0.51 %). DISCUSSION: With regard to the aspects mentioned above, the
      TEP-procedure provided excellent results in the examined patient cohort and
      therefore turned out to be at least comparable with competitive endoscopic
      methods. A remarkable new finding was that patients could go back to work on
      average 2 weeks earlier than regaining their everyday fitness.

PMID- 15965882
TI  - Management of massive presacral bleeding during low pelvic surgery -- an
      alternative technique.
AB  - Although massive presacral bleeding during rectal mobilization is uncommon, it
      can rapidly destabilize a patient. So, effective hemostasis is critical in severe
      presacral hemorrhage due to the fatal course of this complication. Among the
      reported methods are packing, thumbtacks, inflatable devices, muscle tamponade,
      muscle fragment welding and application of endoscopic staplers. Local hemostatic
      agents in conjunction with other methods such as diathermy, cyanoacrylate tissue
      adhesives and application of bone wax are among other alternatives which may help
      to treat this serious complication. The aim of this study is to describe the
      anatomic and physiologic basis of our mode of treatment, which is new in the
      literature approach, treating two patients with presacral bleeding during low
      anterior resection for rectal cancer. The technique is the early clamping of the
      infrarenal aorta and suture ligation of the bleeding points from the presacral
      plexus.

PMID- 15965883
TI  - Retroperitoneal perforation of a duodenal diverticulum with colonic necrosis --
      report of a case.
AB  - Primary duodenal diverticula are usually asymptomatic. About 115 perforations
      have been reported, but none with right colon necrosis. We report a 45-year-old
      woman, with a five days history of high fever along with epigastric and
      periumbilical pain. Physical examination revealed right upper and lower quadrant
      tenderness with peritoneal signs. White blood cell count was 11 500/mm (3) while
      biochemical and hepatic biology tests were normal. Abdominal radiographs showed
      no pathologic findings. Ultrasound disclosed fluid in the lower pelvis.
      Computerized tomography revealed fluid collection in the right hepatorenal space.
      Intraoperative findings included purulent fluid in the lower pelvis, segmental
      necrotic changes of the right colon, and a perforated diverticulum on the
      antimesenteric border of the third part of the duodenum. Surgery consisted of
      right hemicolectomy and ileo-transverse anastomosis, diverticulectomy, and
      decompressive lateral duodenostomy at the second duodenal portion. The patient
      had an uneventful postoperative course. A contrast study from the duodenostomy
      tube on the 6 (th) postoperative day showed no leakage or obstruction.
      Duodenostomy tube was removed on the 14 (th) postoperative day. Histology
      confirmed the diagnosis of a primary duodenal diverticulum.

PMID- 15965884
TI  - [Terminolateral esophagojejunostomy after gastrectomy with the biofragmentable
      anastomosis ring in the dog model].
AB  - INTRODUCTION: Esophagojejunostomy after total gastrectomy still remains a high
      risk anastomosis with a considerable morbidity and mortality. The majority of
      these anastomoses are performed by the intraluminal stapler technique, yet
      stenoses are a known late complication even after an uneventful postoperative
      course. In the present study, the osophagojejunostomy with the biofragmentable
      anastomosis ring (BAR) was examined in dogs. METHODS: 28 dogs were randomized
      into a group of manual suture (n = 14) and a BAR-group (n = 14). After
      gastrectomy, the esophagojejunostomy was performed by hand-suture with
      polypropylene 4-0 in the manual suture group, and with the 25/1.5 mm BAR in the
      BAR-group. In both groups the Roux-en-Y jejunojejunostomy was performed by hand
      suture. The dogs were evaluated on postoperative days 4, 7 and 14 with regard to
      macroscopy, bursting strength, tissue hydroxyproline and histology. RESULTS:
      There was one leakage without clinical effect in the hand-sewn group on
      postoperative day 4; there was no leak in the BAR-group. In observing fibre-free
      enteral feeding, neither functional disorders nor obstruction of the BAR were
      observed. The general anastomosis parameters were matchable between the groups.
      CONCLUSION: The infracarinal BAR-esophagojejunostomy is comparable to the hand
      sewn anastomosis in the dog-model.

PMID- 15965885
TI  - Biosynthesis of C14-labeled amino acids by Chlorella ellipsoidae.

PMID- 15965886
TI  - Hereditary variation and genetic recombination in Koji-molds (Aspergillus oryzae
      and Asp. sojae). I. Natural variation.
AB  - Natural variation in monospore lines of Koji-molds (Asp. oryzae and Asp. sojae),
      isolated from commercial Koji material or soil and from laboratory stock
      cultures, has been observed. We can divide the 58 strains of Koji-molds
      investigated into two groups; one group consists of inconstant strains which are
      very liable to produce natural variants, and the other consists of strains which
      remain constant through successive single spore culture. The inconstant strains
      develop colonies bearing various proportions of conidia and aerial mycelium (X
      type). They generally form large conidia (Asp. oryzae var. magnasporus) but
      sometimes medium sized conidia (Asp. oryzae s. str.), which produce large conidia
      occasionally. The colonies of the constant strains show abundant conidial
      formation and smooth surfaces (C-type). The conidia are mostly small (Asp. oryzae
      var. microsporus) but sometimes medium in size (Asp. oryzae s. str.). The colony
      types of the variants are as follows: C (Conidial type, whole colony covered with
      conidia), M (mycelial type), R (restricted in growth rate), St (sterile type,
      little sporulation on all media tested), Nit (requiring reduced nitrate, very
      faint growth on Czapek's agar), and LS (semi lethal, growth cease immediately
      after germination). Pedigree cultures of the 8 inconstant strains have been made,
      but no definite segregation ratios for each variant type have been recognized
      through successive generations. The LS and N types commonly occur spontaneously
      from the M-type.

PMID- 15965887
TI  - Hiochic acid, a new growth factor for Lactobacillus homohiochi and Lactobacillus
      heterohiochi.

PMID- 15965888
TI  - Studies on the amino acid fermentation. Part 1. Production of L-glutamic acid by
      various microorganisms.
AB  - Screening tests for glutamate producing strains were carried out, with the media
      containing carbohydrate and ammonia source as chief ingredients. Glutamate as
      well as certain other amino acids was detected by paper chromatography in culture
      broth of many microorganisms tested. Accumulation of L-glutamate in a significant
      amount (at least a few mg of glutamate per ml of broth) has been demonstrated by
      various strains of bacteria, streptomycetes, yeasts, and fungi. The highest level
      of glutamate production has been obtained by a new species of Micrococcus,
      yielding as much as 0.25 mole of it from one mole of glucose. The courses of
      fermentations mainly by known strains of microorganisms are shown. The importance
      of the cultural condition and strain specificity for the production of amino
      acids are briefly described.

PMID- 15965889
TI  - Accumulation of allo-isocitric acid by a Penicillium strain.
AB  - The occurrence of L(S)-allo-isocitric acid in nature, as a new fungal product,
      was first found in the culture medium of Pen. purpurogenum Stoll var. rubri
      sclerotium Thom. No. 1148. The acid was obtained as its gamma-lactone in a
      crystalline form. Some chemical and physical characters were described. The acid
      was the only one detectable acid accumulated by its fungus in the given
      condition, and the yield of the acid by weight exceeded about 70% of the consumed
      glucose.

PMID- 15965890
TI  - DNA base composition, susceptibility to bacteriophages and interspecific
      transformation as criteria for classification in the genus Bacillus.
AB  - With 25 strains belonging to 12 species of the genus Bacillus, the base
      composition of DNA, the susceptibility to bacteriophages, and the ability to
      transform Bacillus subtilis strain Marburg were studied. Analyses of phage DNAs
      were also performed. The results were as follows: (1) The DNA base compositions
      were not uniform even among strains belonging to one taxonomic species. (2) The
      DNAs extracted from B. natto, B. megaterium and B. polymyxa could transform
      genetic traits of B. subtilis Marburg although the frequencies were not equal.
      (3) The host ranges of some temperate bacteriophages were correlated with the
      taxonomical data. On these bases, the phylogenetic relatedness of B. subtilis to
      B. megaterium was discussed.

PMID- 15965891
TI  - Conserved portion in bacterial ribosomal RNA.
AB  - The conserved portion in bacterial ribosomal RNA was studied by the DNA-RNA
      hybridization method. The hybridization percentages were as follows: Bacillus
      subtilis DNA and B. subtilis 23S rRNA, 0.16; Escherichia coli DNA and E. coli 23S
      rRNA, 0.15; B. subtilis DNA and E. coli 23S rRNA, 0.03; E. coli DNA and B.
      subtilis 23S rRNA, 0.04. The RNA's extracted from the heterologous hybrids could
      be rehybridized with DNA's of B. subtilis and E. coli. The average chain lengths
      of the RNA's were estimated by sucrose density gradient centrifugation and
      Sephadex gel filtration. The results suggested that the size might be larger than
      30 nucleotides. Nucleotide compositions of the RNA's in the hybrids were also
      studied. Both RNA's contained higher molar percentages of guanylic acid and
      cytidylic acid than the whole rRNA's.

PMID- 15965892
TI  - Separation and determination of active components in Schisandra chinensis Baill.
      and its medicinal preparations by non-aqueous capillary electrophoresis.
AB  - A simple, economical and effective non-aqueous capillary electrophoresis
      separation and detection method was developed for the quantification of
      deoxyschizandrin and gamma-schizandrin in Schisandra chinensis Baill. and its
      medicinal preparations for the first time. After optimization of separation
      conditions, a buffer of 140 mmol/L sodium cholate in methanol was selected for
      separating the two analytes, but baseline separation of SA and SB in real samples
      was not obtained. Therefore second-order derivative electropherograms were
      applied for resolving overlapping peaks. Regression equations revealed good
      linear relationships (correlation coefficients 0.9975--0.9988) between peak
      heights in second-order derivative electropherograms and concentrations of the
      two analytes. The relative standard deviations (RSD) of the migration times and
      the peak height of the two constituents were in the ranges 0.62--0.79% and 0.25-
      2.17% (intra-day) and 1.43--2.06 and 4.08--5.72% (inter-day), respectively. The
      recoveries of the two constituents ranged from 93.2 to 103.0%. The results
      indicated that baseline separation of the analytes was sometimes hard to obtain
      in real samples and second-order derivative electropherograms were applicable for
      the resolution and analysis of overlapping peaks.

PMID- 15965893
TI  - Methodological issues related to exhaled nitric oxide measurement in children
      aged four to six years.
AB  - This study was designed to test five methodological issues related to measurement
      of fractional exhaled nitric oxide (FE(NO)) in children aged 4-6 years using
      commercially available apparatus. Participants attended two randomly selected
      schools. A respiratory questionnaire was completed. Measurements of FE(NO) were
      made on successive days, using a NIOX analyzer employing standard or modified
      methodologies. Ninety-one children participated in the study (mean age, 5.3
      years; 46 boys). Using a standard methodology (n = 61), FE(NO) was successfully
      measured in 28 (46%) children, 1/12 aged 4 years, 12/25 aged 5 years, and 15/24
      aged 6 years (trend test P = 0.01). On the first assessment, FE(NO) could be
      determined in more boys than girls (64% vs. 30%, respectively, P = 0.008), but
      this gender difference was not apparent on the second assessment. Exhaled NO was
      reproducible over a 24-hr period; the mean difference between repeated
      measurements of natural log (ln) FE(NO) was 0.016 parts per billion (ppb) (95%
      confidence limits, -0.479, 0.511), n = 20. Data from 35 assessments showed that
      values of FE(NO) did not alter over nine individual, successive measurements. Use
      of a modified methodology in 30 children increased success in obtaining FE(NO),
      but these values were unreliable. In conclusion, measurements of FE(NO) can be
      obtained in the majority of 5- and 6-year-old but not 4-year-old children.
      Exhaled NO measurements were reproducible over a 24-hr interval, and did not
      change over up to nine expiratory maneuvers in these young children.

PMID- 15965894
TI  - Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus
      with and without cystic fibrosis.
AB  - Over 90% of cystic fibrosis (CF) patients are treated with bronchodilators, and
      6% have diabetes. Some with asthma also have diabetes, and most are treated with
      bronchodilators. Systemic administration of adrenergic agents can cause increases
      in blood glucose, but the effect of inhaled agents is unclear. A double-blind
      study was performed on 10 patients with type 1 diabetes mellitus (DM) without CF
      (3 male, 7 female, mean age 25.5 years) and 9 patients with insulin-dependent CF
      related diabetes (CFRD) (8 male, 1 female, mean age 21.9 years). On 2 separate
      days before 9 AM fasting and the morning dose of insulin, 2.5 mg of albuterol or
      nebulized placebo were given. Blood glucose was measured by finger stick with a
      glucose reflectance meter before and 15, 30, 45, and 60 min after treatment. No
      significant changes from baseline or differences between placebo and albuterol
      occurred in either group. The mean maximum increase from baseline in DM was 20
      mg/dl on placebo, and 38 mg/dl on albuterol; in the CFRD, the respective changes
      were 7 and 7 mg/dl. Two DM patients had a > 50 mg/dl increase on albuterol vs.
      placebo; no CFRD patients had differences of such magnitude. DM patients had
      greater increases from baseline than CFRD patients on placebo and albuterol.
      Differences reached statistical significance at 30 and 45 min on placebo, and 45
      min on albuterol. Albuterol 2.5 mg by nebulizer causes no clinically significant
      increases in blood glucose in DM or CFRD patients. Diabetes patients without CF
      have a significantly greater increase of glucose with time (placebo or albuterol)
      than CFRD patients.

PMID- 15965895
TI  - Similarities and dissimilarities of branching and septation during lung
      development.
AB  - The lungs of small premature babies are at a developmental stage of finalizing
      their airway tree by a process called branching morphogenesis, and of creating
      terminal gas exchange units by a mechanism called septation. If the branching
      process is disturbed, the lung has a propensity to be hypoplastic. If septation
      is impaired, the terminal gas exchange units, the alveoli, tend to be enlarged
      and reduced in number, an entity known as bronchopulmonary dysplasia. Here, we
      review current knowledge of key molecules influencing branching and septation. In
      particular, we discuss the molecular similarities and dissimilarities between the
      two processes of airspace enlargement. Understanding of the molecular mechanisms
      regulating branching and septation may provide perinatologists with targets for
      improving lung growth and maturation.

PMID- 15965896
TI  - Twitch airway pressure elicited by magnetic phrenic nerve stimulation in
      anesthetized healthy children.
AB  - Children with diaphragm dysfunction may be unable to maintain adequate
      ventilation. Accurate diagnosis is important, but can only be achieved using an
      appropriate test and reference range. The aim of this study, therefore, was to
      measure diaphragm contractility and examine the influence of age and maturation,
      using magnetic phrenic nerve stimulation in healthy children. Anterolateral
      magnetic stimulation (MS) of the phrenic nerves was performed using a 43-mm
      figure-eight coil in 23 children (14 male; mean age, 7.8 years; range, 1.8-15.7)
      anesthetized for minor surgery with sevoflurane gas. The airway was maintained
      with a cuffed laryngeal mask airway (LMA) which was briefly occluded during MS.
      Diaphragm contractility was assessed by measuring the airway pressure (TwPaw)
      elicited by MS. TwPaw responses were obtained in all subjects, with mean (SD)
      TwPaw 18.2 (6.8) cm H2O bilateral, 7.3 (3.2) cm H2O left unilateral, and 8.6
      (3.1) cm H2O right unilateral. Subgroup analysis was performed in 17 of the
      children who were prepubertal. Their mean (SD) TwPaw was 17.3 (6.8) cm H2O
      bilateral, 7.1 (3.7) cm H2O left unilateral, and 8.3 (3.3) right unilateral. The
      mean (SD) intrapatient coefficients of variation for bilateral and left and right
      unilateral TwPaw were 8.4% (5.2), 6.7% (3.5), and 11.7% (10.3), respectively.
      Bilateral and left and right unilateral TwPaw were significantly related to age
      (P < 0.05). In healthy prepubertal children, diaphragm contractility is primarily
      influenced by age.

PMID- 15965897
TI  - Persistent tachypnea of infancy is associated with neuroendocrine cell
      hyperplasia.
AB  - We sought to determine the clinical course and histologic findings in lung
      biopsies from a group of children who presented with signs and symptoms of
      interstitial lung disease (ILD) without identified etiology. Patients were
      identified from the pathology files at the Texas Children's Hospital who
      presented below age 2 years with persistent tachypnea, hypoxia, retractions, or
      respiratory crackles, and with nonspecific and nondiagnostic lung biopsy
      findings. Age-matched lung biopsy controls were also identified. Their clinical
      courses were retrospectively reviewed. Biopsies were reviewed, and immunostaining
      with antibodies to neuroendocrine cells was done. Fifteen pediatric ILD patients
      and four control patients were identified for inclusion in the study. Clinically,
      the mean onset of symptoms was 3.8 months (range, 0-11 months). Radiographs
      demonstrated hyperinflation, interstitial markings, and ground-glass densities.
      Oxygen was initially required for prolonged periods, and medication trials did
      not eliminate symptoms. After a mean of 5 years, no deaths had occurred, and
      patients had improved. On review of the lung biopsies, all had a similar
      appearance, with few abnormalities noted. Immunostaining with antibodies to
      neuroendocrine cell products showed consistently increased bombesin staining.
      Subsequent morphometric analysis showed that immunoreactivity for bombesin and
      serotonin was significantly increased over age-matched controls. In conclusion,
      we believe this may represent a distinct group of pediatric patients defined by
      the absence of known lung diseases, clinical signs and symptoms of ILD, and
      idiopathic neuroendocrine cell hyperplasia of infancy. These findings may be
      important for the evaluation of ILD in young children.

PMID- 15965898
TI  - Cystic fibrosis and Russell-Silver syndrome in a child with maternal isodisomy of
      chromosome 7.
AB  - A 6-year-old Asian girl was diagnosed with cystic fibrosis at 3 months of age,
      following investigations for failure to thrive. She had intrauterine growth
      retardation and continued to have restricted postnatal growth, despite adequate
      caloric intake and enzyme replacement therapy. Further investigations were
      initiated when she was 5 years old, as her growth was not responding to the usual
      treatment measures. These tests revealed that she had maternal isodisomy of
      chromosome 7.

PMID- 15965899
TI  - Survey of professionals' expectations of developmental task achievement of cystic
      fibrosis self-care in children.
AB  - We surveyed 174 professionals with at least 6 months of experience working with
      children and adolescents with cystic fibrosis (CF), to obtain estimates of ages
      at which 50% of children with CF may be able to perform each of 44 self-care
      behaviors related to the treatment of CF. Respondents were 63 physicians, 36
      nurses, 24 dietitians, 18 respiratory therapists, 17 nurse practitioners, 10
      social workers, and 4 psychologists, who had a mean of 11.4 years (SD = 7.5) of
      experience working with pediatric patients with CF. Mean age estimates for self
      care behaviors ranged from 5.5-13.9 years. For each item, responses varied among
      respondents, as reflected by a mean standard deviation of 2.75 years for all
      behaviors. Analyses of concordance suggested a high level of agreement among
      respondents for the order of mastery of specific skills related to diet and
      enzymes use only. To date, there are no empirically defined age estimates for
      when children with CF may be able to perform specific self-care behaviors
      involved in the management of CF. This survey is the first step in generating age
      estimates for self-care independence in CF. Future research should conduct an
      objective assessment of children's CF knowledge and skill in performing these
      behaviors, and compare these findings to the age estimates offered in this study.

PMID- 15965900
TI  - Management of empyema in children.
AB  - The incidence of empyema complicating community-acquired pneumonia is increasing
      and causes significant childhood morbidity. Pneumococcal infection remains the
      most common isolated cause in developed countries, with Staphylococcus aureus the
      predominant pathogen in the developing world. Newer molecular techniques
      utilizing the polymerase chain reaction have led to an increase in identification
      of causative bacteria, previously not isolated by conventional culture
      techniques. This remains an important epidemiological tool, and may help in
      guiding correct antibiotic use in the future. There are many treatment options,
      however, and the care a child currently receives is dependent on local practice,
      which is largely determined by availability of medical personnel and their
      preferences. Although there are many reported case series comparing treatment
      options, only two randomized controlled studies exist to guide treatment in
      children. There is an urgent need for this to be addressed, particularly with the
      introduction of relatively new surgical techniques such as video-assisted
      thorascopic surgery.

PMID- 15965901
TI  - Lung volumes in healthy Afro-Caribbean children aged 4-17 years.
AB  - Lung volumes in healthy children differ according to their ethnic origin. We
      wished to determine if any differences in the lung volumes of Afro-Caribbean (AC)
      children from those predicted by Caucasian reference values disappeared if the
      results were related to sitting height or to 90% or 77% of lung volumes predicted
      for height from Caucasian reference values based on standing height. We took, as
      our working hypothesis, that it is inappropriate to use Caucasian reference
      values to interpret data from Afro-Caribbean children, and that ethnic-specific
      reference values are required. This was a prospective, observational study.
      Subjects included 80 AC children with a median age of 9 (range, 4.3-17.8) years.
      Standing and sitting height were measured. Lung volumes were measured by body
      plethysmography (total lung capacity, TLC(pleth); functional residual capacity,
      FRC(pleth); and vital capacity, VC(pleth)), helium gas dilution (functional
      residual capacity, (FRC(He)), spirometry (forced expiratory volume in 1 sec,
      FEV(1)), and forced vital capacity (FVC). The lung volumes of AC children
      correlated significantly with standing height, but differed significantly from
      values predicted from Caucasian reference values based on standing height (P <
      0.05). Significant differences remained for TLC(pleth), FRC(pleth), FRC(He),
      RV(pleth), VC(pleth), FEV(1), and FVC when the results were related to sitting
      height or 90% or 77% of values predicted from Caucasian reference values based on
      height (P < 0.05). Lung volumes in Afro-Caribbean children should be compared to
      ethnic-specific reference values.

PMID- 15965902
TI  - Intracellular water homeostasis and the mammalian cellular osmotic stress
      response.
AB  - The cellular response to osmotic stress ensures that the concentration of water
      inside the cell is maintained within a range that is compatible with biologic
      function. Single cell organisms are particularly dependent on mechanisms that
      permit adaptation to osmotic stress because each individual cell is directly
      exposed to the external environment. Mammals, however, limit osmotic stress by
      establishing an internal aqueous environment in which intravascular water and
      electrolytes are subject to sensitive and dynamic, organism-based homeostatic
      regulation. Recent studies of NFAT5/TonEBP, an essential mammalian osmoregulatory
      transcription factor, demonstrate the unexpected yet critical significance of
      cell-based osmotic regulation in vivo. These results highlight the fundamental
      importance of maintaining intracellular water homeostasis in the face of varying
      cellular metabolic activity and distinct tissue microenvironments.

PMID- 15965903
TI  - Polyamine depletion inhibits apoptosis following blocking of survival pathways in
      human chondrocytes stimulated by tumor necrosis factor-alpha.
AB  - Chondrocyte apoptosis can be an important contributor to cartilage degeneration,
      thereby making it a potential therapeutic target in articular diseases. To search
      for new approaches to limit chondrocytic cell death, we investigated the
      requirement of polyamines for apoptosis favored by tumor necrosis factor-alpha
      (TNF), using specific polyamine biosynthesis inhibitors in human chondrocytes.
      The combined treatment of C-28/I2 chondrocytes with TNF and cycloheximide (CHX)
      resulted in a prompt effector caspase activation and internucleosomal DNA
      fragmentation. Pre-treatment of chondrocytes with alpha-difluoromethylornithine
      (DFMO), an ornithine decarboxylase (ODC) inhibitor, markedly reduced putrescine
      and spermidine content as well as the caspase-3 activation and DNA fragmentation
      induced by TNF and CHX. DFMO treatment also inhibited the increase in effector
      caspase activity provoked by TNF plus MG132, a proteasome inhibitor. DFMO
      decreased caspase-8 activity and procaspase-8 content, an apical caspase
      essential for TNF-induced apoptosis. Although DFMO increased the amount of
      active, phosphorylated Akt, inhibitors of the Akt pathway failed to restore the
      TNF-induced increase in caspase activity blunted by DFMO. DFMO also reduced the
      increase in caspase activity induced by staurosporine, but in this case Akt
      inhibition prevented the DFMO effect. Pre-treatment with CGP 48664, an S
      adenosylmethionine decarboxylase (SAMDC) inhibitor markedly reduced spermidine
      and spermine levels, and provoked effects similar to those caused by DFMO.
      Finally DFMO was effective even in primary osteoarthritis (OA) chondrocyte
      cultures. These results suggest that the intracellular depletion of polyamines in
      chondrocytes can inhibit both the death receptor pathway by reducing the level of
      procaspase-8, and the apoptotic mitochondrial pathway by activating Akt.

PMID- 15965904
TI  - TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic
      indicators in laryngeal squamous cell carcinoma.
AB  - To prospectively evaluate the prognostic significance of TP53, H-, K-, and N-Ras
      mutations, DNA-ploidy and S-phase fraction (SPF) in patients affected by locally
      advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median
      follow-up was 71 months) who underwent resective surgery for primary operable
      locally advanced LSCC were analyzed. Tumor DNA was screened for mutational
      analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed by flow
      cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the
      TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triple
      mutations. In total, 46 TP53 mutations were observed. The majority (41%) of these
      occur in exon 5 (19/46), while the mutations in exons 6, 7, and 8 were
      represented in 14, 7, and 6 patients, respectively (31%, 15%, and 16%). Five LSCC
      patients (6%) showed a mutation in H-Ras gene. Sixty-three percent of the cases
      (51/81) were DNA aneuploidy, 14% of these (7/51) were multiclonal. Thirty-nine
      patients (48%) had an high SPF value. At Univariate analysis, the DNA aneuploidy,
      high SPF (>15.1%), TP53 mutations and, in particular, the mutations that occur in
      exons 5 and 8 were significantly related to quicker disease relapse and short OS.
      At Multivariate analysis, the major significant predictors for both disease
      relapse and death were high SPF and any TP53 mutations. While histological grade
      G3 was an independent factor only for relapse. In conclusions, any TP53 mutations
      and high SPF are important biological indicators to predict the outcome of LSCC
      patients.

PMID- 15965905
TI  - CASK localizes to nuclei in developing skeletal muscle and motor neuron culture
      models and is agrin-independent.
AB  - Membrane-associated guanylate kinases (MAGUKs) are cytoplasmic multi-domain
      proteins that serve as scaffold proteins at cell junctions and synapses.
      Calmodulin-associated serine/threonine kinase (CASK) stabilizes the integrity of
      synapses in the brain. Additionally, CASK is capable of acting as a
      transcriptional co-activator and localizes to neuronal nuclei in the developing
      brain. We have recently described CASK localization to both the pre- and post
      synaptic membranes of the neuromuscular junction (NMJ), where it forms a complex
      with discs large (Dlg). CASK also localizes to some, but not all nuclei in adult
      mouse skeletal muscle. To begin to dissect the roles of CASK in the cellular
      components of the NMJ, we investigated the localization of CASK during
      differentiation in cell culture models of skeletal muscle and motor neurons. We
      demonstrate that CASK localizes to the nucleus in undifferentiated myoblasts, but
      is pre-dominantly in the cytoplasm in differentiated myotubes of the C2C12
      myogenic cell line. We also show nuclear localization of both CASK and Dlg in a
      motor neuron-neuroblastoma hybrid cell line, MN-1, suggesting a role for CASK and
      Dlg in nuclei of neurons in the peripheral nervous system. Finally, we
      demonstrate that CASK and Dlg do not co-cluster with acetylcholine receptors in
      C2C12 myotubes in response to agrin or laminin treatment, suggesting a novel
      mechanism of recruitment to the NMJ that is independent of acetylcholine receptor
      and utrophin complexes. These studies delineate important developmental
      characteristics of CASK and Dlg, and suggest dual roles for these proteins in
      both the skeletal muscle and motor neuron components of the NMJ.

PMID- 15965906
TI  - T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing
      nuclear interaction between IRS-1 and Rad51.
AB  - JC polyomavirus (JCV), which infects 90% of the human population, is detectable
      in human tumors. Its early protein, JCV T-antigen, transforms cells in vitro and
      is tumorigenic in experimental animals. Although T-antigen-mediated
      transformation involves genetic alterations of the affected cells, the mechanism
      underlying this genomic instability is not known. We show that JCV T-antigen
      inhibits homologous recombination DNA repair (HRR), which results in an
      accumulation of mutations. T-antigen does not operate directly but utilizes a
      cytosolic molecule, insulin receptor substrate 1 (IRS-1). Following T-antigen
      mediated nuclear translocation, IRS-1 binds Rad51 at the site of damaged DNA.
      This T-antigen-mediated inhibition of HRR does not function in cells lacking IRS
      1, and can be reproduced in the absence of T-antigen by IRS-1 with artificial
      nuclear localization signal. Our observations define a new mechanism by which
      viral protein utilizes cytosolic molecule to inhibit faithful DNA repair, and
      suggest how polyomaviruses could compromise stability of the genome. (c) 2005
      Wiley-Liss, Inc.

PMID- 15965907
TI  - Micronodular thymoma: an epithelial tumour with abnormal chemokine expression
      setting the stage for lymphoma development.
AB  - The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although
      thymic follicular lymphoid hyperplasia (TFH) is commonly associated with
      myasthenia gravis (MG), lymphoma is not a complication of this condition. The
      present paper reports a high frequency of monoclonal B-cell populations (6 of 18
      cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm
      with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25
      cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural
      lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of
      the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and
      thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic
      epithelium of MNTs, but not of TFH and other types of thymoma, expressed high
      levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18,
      CCR6, and CCL20. It is concluded that abnormal chemokine expression in an
      epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of
      monoclonal B cells, and, eventually, the subsequent development of mediastinal
      lymphomas. More generally, the concept that expression of a 'high-risk' spectrum
      of chemokines due to local or genetic factors may interfere with B-cell
      homeostasis and may contribute to MALT lymphoma development in chronic
      inflammatory states is proposed.

PMID- 15965908
TI  - Isolated crypts form spheres prior to full intestinal differentiation when grown
      as xenografts: an in vivo model for the study of intestinal differentiation and
      crypt neogenesis, and for the abnormal crypt architecture of juvenile polyposis
      coli.
AB  - We describe a model system in which single crypts, isolated from newborn rats,
      were embedded in a type I collagen gel and subcutaneously grafted to the flanks
      of nude mice, whereupon they underwent full intestinal morphogenesis. Small
      fragments of small intestine and colon were incubated with the divalent cation
      chelator EDTA, resulting in the release of crypts and villi. Released crypts were
      then suspended sparsely in type I collagen gel. Segments of gel containing a
      single crypt were grafted subcutaneously into a nude mouse. Grafts were harvested
      at weekly intervals. By 2 days, the mouth of the crypts had joined to seal the
      crypt and, within 1 week, the structure ballooned to form a spherical cystic
      structure lined by flattened epithelial cells showing no evidence of
      cytodifferentiation. After 2 weeks, host stromal cells had invaded the collagen
      and settled around this spherical crypt. At points where stromal cells appeared
      in contact with the crypt, the epithelium exhibited a more columnar phenotype. By
      4 weeks, the 'crypt sphere' was surrounded by stroma expressing alpha-smooth
      muscle actin and, at this time, multiple buds appeared that gave rise to new
      crypts. By 5 weeks, villi had formed and cell lineages associated with the small
      intestine and colon were present; the original single crypt had transformed into
      a functional intestinal unit. Therefore, we have shown that a single crypt has
      the potential to grow, give rise to other crypts and dependent structures such as
      villi. This model has considerable potential for use in gene transfer experiments
      in the study of intestinal differentiation, and for the analysis of crypt
      neogenesis via crypt fission. Moreover, the appearances showed a close
      resemblance to those seen in juvenile polyposis syndrome (JPS), where the budding
      and fission of single crypts isolated by stromal overgrowth offers an alternative
      explanation for the histogenesis of JPS.

PMID- 15965909
TI  - Hydroxy apatite microspheres enhance gap junctional intercellular communication
      of human osteoblasts composed of connexin 43 and 45.
AB  - The aseptic loosening of artificial joints with associated periprosthetic bone
      resorption may be partly due to the suppression of osteoblast function to form
      new bone by wear debris from the joint. To assess the effect of wear debris on
      osteoblasts, effects of model wear debris on gap junctional intercellular
      communication (GJIC) of normal human osteoblasts were estimated. The GJIC
      activity of the osteoblasts after a 1-day incubation with the microspheres was
      similar to that of normal osteoblasts. However, hydroxy apatite particles, which
      have been reported to enhance the differentiation of osteoblasts in contact with
      them, enhanced the GJIC function of the osteoblasts. From RT-PCR studies, not
      only connexin 43 but also connexin 45 is suggested to play a role in the GJIC of
      the osteoblasts in an early stage of coculture with the microspheres, although it
      is still unclear how these connexins work and are regulated in the GJIC and
      differentiation. However, this study suggests that there is a relationship
      between the early levels of GJIC and the differentiation of the cells. Therefore,
      estimating the effect of biomaterials, even in the microsphere form, on the GJIC
      of model cells, with which the biomaterials may be in contact in vivo, can
      provide important information about their biocompatibility.

PMID- 15965910
TI  - Scaffold mesh size affects the osteoblastic differentiation of seeded marrow
      stromal cells cultured in a flow perfusion bioreactor.
AB  - In this study, we cultured marrow stromal cells on titanium fiber meshes in a
      flow perfusion bioreactor and examined the effect of altering scaffold mesh size
      on cell behavior in an effort to develop a bone tissue construct composed of a
      scaffold, osteogenic cells, and extracellular matrix. Scaffolds of differing mesh
      size, that is, distance between fibers, were created by altering the diameter of
      the mesh fibers (20 or 40 microm) while maintaining a constant porosity. These
      scaffolds had a porosity of 80% and mesh sizes of 65 microm (20-microm fibers) or
      119 microm (40-microm fibers). Cell/scaffold constructs were grown in static
      culture or under flow for up to 16 days and assayed for osteoblastic
      differentiation. Cellularity was higher at early time points and Ca2+ deposition
      was higher at later time points for flow constructs over static controls. The 20
      microm mesh had reduced cellularity in static culture. Under flow conditions,
      mass transport limitations are mitigated allowing uniform cell growth throughout
      the scaffold, and there was no difference in cellularity between mesh types.
      There was greater alkaline phosphatase (ALP) activity, osteopontin levels, and
      calcium under flow at 8 days for the 40-microm mesh compared to the 20-microm
      mesh. However, by day 16, the trend was reversed, suggesting the time course of
      differentiation was dependent on scaffold mesh size under flow conditions.
      However, this dependence was not linear with respect to time; larger mesh size
      was conducive to early osteoblast differentiation while smaller mesh size was
      conducive to later differentiation and matrix deposition.

PMID- 15965911
TI  - In vitro interaction between surface-treated Ti-6Al-4V titanium alloy and human
      peripheral blood mononuclear cells.
AB  - The Ti-6Al-4V titanium alloy is widely employed as an implant material. The
      effects of Ti-6Al-4V samples, tested in both an untreated state and one in which
      the samples were subjected to a glow-discharge treatment performed with the use
      of air, on human peripheral blood mononuclear cells (PBMC) were studied.
      Apoptosis, undetectable after 24-h contact of PBMC with the two sample types, is
      induced after 48 h by treated samples, and, after 48 h, but in the presence of
      1.5 microg/mL PHA, by both sample types. The expression of intercellular adhesion
      molecule-1 (ICAM-1) always increases, in comparison with control, in PBMC put in
      contact with the two sample types. In the same way, a remarkable increase in
      tumor necrosis-alpha (TNF-alpha) release in the culture medium is registered,
      when PBMC are put in contact with the two sample types for 24 and 48 h. Human
      umbilical-vein endothelial cells (HUVEC) cocultured for 48 h with PBMC,
      previously incubated with the two sample types for 24 h, show an increase in ICAM
      1 and vascular cell adhesion molecule-1 (VCAM-1) protein expression in comparison
      with control (HUVEC cocultured with control PBMC), indicating that inflammatory
      phenomena might occur. Taken together, these results suggest that, although
      plasma-treated titanium alloy shows a better biocompatibility in comparison with
      the untreated one, attention must be paid to the careful control of the first
      signs of inflammation.

PMID- 15965912
TI  - Microstructural effects on the wear resistance of wrought and as-cast Co-Cr-Mo-C
      implant alloys.
AB  - The tribological behavior of two cobalt-base alloys-an as-cast high-carbon and a
      wrought low-carbon Co alloy-that are used as hip implant materials is examined in
      this work. This work discusses the experimental results of cobalt-cobalt wear
      pairs, in wrought and as-cast conditions, where the amount of hexagonal phase is
      systematically modified through an isothermal aging treatment. Fully FCC and HCP
      Co alloys are tested versus alloys with various volume fractions of HCP phase
      (0.05 to 1.0 volume fractions). Preliminary results indicate that Co-Cr-Mo/Co-Cr
      Mo alloy pairs both possessing an HCP matrix microstructure tend to exhibit
      outstanding wear properties.

PMID- 15965913
TI  - Interactions of acinar cells on biomaterials with various surface properties.
AB  - The purpose of this study is to evaluate the interactions of rat parotid acinar
      cells on biomaterials with different surface properties. The biomaterials used in
      this study included polyvinyl alcohol (PVA), chitosan, poly (ethylene-co-vinyl
      alcohol) (EVAL), and polyvinylidene fluoride (PVDF). Cell morphology was observed
      by photomicroscope. Cell growth and differentiated characteristic function were
      separately assayed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide (MTT) reduction activity and amylase activity. Results indicated that
      behaviors of acinar cells on materials might differ to a great extent depending
      on the surface hydrophilicity and morphology of the materials. On the relatively
      hydrophobic materials, the abilities of acinar cells to adhere and proliferate
      increased simultaneously. In addition, porous PVDF had higher cell growth
      compared with dense PVDF. Therefore, the hydrophobic PVDF with a porous structure
      was the best substrate for culturing acinar cells. According to our findings, a
      tubular PVDF scaffold with dense outer surface to prevent saliva leakage and with
      porous inner surface for the cell growth was proposed to serve as an artificial
      salivary gland for future use in the treatment of patients with salivary
      hypofunction.

PMID- 15965914
TI  - Delivering the nuts without the bolts: the plight of clinical psychology
      practice.
AB  - A vision as bold as that expressed by C.R. Snyder and Timothy R. Elliott in their
      target article, "Twenty-First Century Graduate Education in Clinical Psychology:
      A Four Level Matrix Model" (this issue, pp 1033-1054), should make the long
      awaited breakthrough in training that would include development, implementation,
      and evaluation of large-scale health delivery systems. The realization that
      clinical psychology is part of the health care industry, and not just
      psychotherapy or mental health, would enable psychologists to go beyond the
      laboratory and become important decision makers in the health care arena and thus
      command a greater share of health care funding.

PMID- 15965915
TI  - Perspectives on education and training in clinical psychology: integrating
      reactions.
AB  - Reacting to the conceptual matrix of C.R. Snyder and T.R. Elliott as described in
      their article, "Twenty-First Century Graduate Education in Clinical Psychology: A
      Four Level Matrix Model" (this issue, pp. 1033-1054), a perspective is provided
      through the roles of a clinical training director and a clinical child and
      pediatric psychologist. Changing the direction of clinical psychology is
      complicated but the subfield of pediatric psychology demonstrates how such
      changes can be integrated with a focus on healthy development and promotion of
      strengths, on policy and public health concerns, and on program evaluation.

PMID- 15965916
TI  - Clinical psychology in the twenty-first century: the wheel remains round.
AB  - The authors C.R. Snyder and T.R. Elliott in their article, "Twenty-First Century
      Graduate Education in Clinical Psychology: A Four Level Matrix Model" (this
      issue, PP. 1033-1054), reflect on the nature of training needed for optimal
      clinical psychologists, and offer suggestions for such training within a matrix
      model. Their position is largely consistent with current American Psychological
      Association preferences and general training guidelines, and has historical
      precedence. Indeed, the ideas, though not new or radical, are very sound. Amen,
      the wheel remains round.

PMID- 15965917
TI  - Graduate education in clinical psychology for the twenty-first century: educating
      psychological health care providers.
AB  - This comment focuses on a topic that is implied but not explicated in C.R. Snyder
      and T.R. Elliott's article (this issue, PP. 1033-1054): The biopsychosocial
      model. I begin by discussing the status of health care, taking up in turn its
      tremendous problems and the negative effects of a system built on mind-body
      dualism. I argue for a transformation of the biomedical system to a
      biopsychosocial system. I then discuss the opportunities for psychology and the
      implications for training.

PMID- 15965918
TI  - Eleven rules for a more successful clinical psychology.
AB  - The recommendations put forth in the target article, "Twenty-First Century
      Graduate Education in Clinical Psychology: A Four Level Matrix Model" (C.R.
      Snyder & T.R. Elliott, this issue, pp. 1033-1054), should be regarded in the
      context of the large need to develop a more progressive and effective discipline.
      No amount of "brute force" education and empiricism is certain to solve the
      problems of the scope of our field identified by the authors. Eleven rules are
      offered and defended that may lead to a more practically and empirically
      successful field.

PMID- 15965919
TI  - Some critical observations on twenty-first century graduate education in clinical
      psychology.
AB  - A number of issues raised in the C.R. Snyder and T.R. Elliott article, "Twenty
      First Century Graduate Education in Clinical Psychology: A Four Level Matrix
      Model" (this issue, pp. 1033-1054), are critically examined: the role of
      interpersonal and societal factors in understanding the human condition, the
      desirability of breadth in both undergraduate and graduate education, political
      and scientific issues in prevention research and application, problems in the use
      of randomized clinical trials for evaluating psychotherapy, and the efficacy
      effectiveness debate in therapy research.

PMID- 15965920
TI  - Jack of all trades, master of none?: an alternative to clinical psychology's
      market-driven mission creep.
AB  - The authors C.R. Snyder and T.R. Elliott of this special issue's target article,
      "Twenty-First Century Graduate Education in Clinical Psychology: A Four Level
      Matrix Model" (this issue, pp. 1033-1054), are right that scientific distinctions
      should sometimes be de-emphasized in service of understanding the larger
      scientific vision. However, they take their combining too far, arrogating unto
      clinical psychology elements best left to their original scholarly disciplines.
      Snyder and Elliott simply present the next logical step in clinical psychology's
      longstanding tradition of "mission creep," broadening its focus to encompass new
      potential markets. Instead, the keeping and sharpening of disciplinary and
      subdisciplinary boundaries might best serve clinical psychology. The emphasis
      would shift from mission creep to building links with complementary disciplines
      and subdisciplines, to tackle issues that require true interdisciplinary
      scholarship.

PMID- 15965921
TI  - Teach our students well: a call for training models that embrace the wisdom of
      the past.
AB  - C.R. Snyder and T.R. Elliott's forward-looking clinical training model (this
      issue, pp. 1033-1054) assumes that traditional clinical theories, particularly
      psychoanalytic theories, have little to offer the study of human strengths. Yet
      the psychoanalytic literature reveals many insights into the nature of strengths
      and weaknesses. This essay describes a three-pronged habit of thinking that has
      led positive psychology advocates, including Snyder and Elliott, to underestimate
      the potential contribution of psychoanalytic models to our understanding of human
      strengths and to training models that stress their importance.

PMID- 15965922
TI  - Another take on the matrix: interactionism.
AB  - This response to C.R. Snyder and T.R. Elliott's article, "Twenty-First Century
      Graduate Education in Clinical Psychology: A Four Level Matrix Model" (this
      issue, PP 1033-1054), focuses on the importance of three types of interactions:
      between mind and body, humans and machines, and individuals and groups. It is
      proposed that the clinical psychology training programs of the future will need
      to ensure that their students are well versed in the relevance of these
      interactions for understanding human behavior and developing effective
      treatments.

PMID- 15965923
TI  - Old wine in new bottles.
AB  - The matrix model as described by C.R. Snyder and T.R. Elliott (this issue, pp.
      1033-1054) is presented as an alternative to the Boulder model of training. In
      fact, it appears to be a reconceptualization of clinical psychology, and this
      newer vision of the field might best be implemented within a Boulder model
      format. The extensive requirements that are developed would best be approached
      through changes in postdoctoral rather than doctoral education. Interestingly,
      professional schools, despite being disparaged, may be the most likely place for
      this model to take root.

PMID- 15965924
TI  - An education for the future.
AB  - The 21st century clinical psychologist will need to become actively engaged in
      establishing our nation's health care policies and priorities to ensure that the
      psychological aspects of care are given greater priority. The clinician's
      workplace and target clientele will drastically change, with the development of a
      global and preventive perspective becoming the key to the profession's future.

PMID- 15965925
TI  - Genotype-phenotype relationships in hepatocellular tumors from mice and man.
AB  - Experimentally induced liver tumors in mice harbor activating mutations in either
      Catnb (beta-catenin) or Ha-ras, according to the carcinogenic treatment. We have
      now investigated by microarray analysis the gene expression profiles in tumors of
      the two genotypes. In total, 364 genes or expressed sequences with aberrant
      expression relative to normal liver were identified, but only 30 of these
      demonstrated unidirectional changes in both tumor types. Several functional
      clusters were identified that involve changes in amino acid utilization and
      ammonia disposition in Catnb-mutated tumors as opposed to alterations in lipid
      and cholesterol metabolism in Ha-ras-mutated tumors. Moreover, several genes
      coding for inhibitory molecules within the Wnt-signaling pathway were upregulated
      in Catnb-mutated tumors, suggesting induction of a negative feedback loop,
      whereas Ha-ras-mutated tumors showed alterations in the expression of several
      genes functional in monomeric G-protein signaling. We conclude that mouse
      hepatoma cells adopt different evolutionary strategies that allow for their
      selective outgrowth under variable environmental conditions. Human hepatocellular
      cancers (HCC) lack RAS mutations but are frequently mutated in CTNNB1, the human
      Catnb ortholog. The set of genes aberrantly expressed in Catnb-mutated mouse
      tumors was used to screen, by expression profiling, for dysregulation of
      orthologous genes within a panel of 25 HCCs, of which 10 were CTNNB1-mutated.
      HCCs with activated beta-catenin displayed a gene expression profile that was
      similar to Catnb-mutated mouse tumors but distinct from the other human HCCs. In
      conclusion, expression fingerprints may be used for diagnostic purposes and
      potential new therapeutic intervention strategies. Supplementary material for
      this article can be found on the HEPATOLOGY website
      (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index/html).

PMID- 15965926
TI  - The modular microarchitecture of human liver.
AB  - The morphological homogeneity of the liver parenchyma has represented a major
      obstacle in finding an acceptable definition of the structural/functional units
      of the liver. Concepts such as the "lobule," the "portal unit" and the "acinus"
      remain debatable. This study investigates the modular microarchitecture on the
      basis of the lobular concept. Using alkaline phosphatase activity as a
      histochemical marker, modules could be recognized clearly. In autopsy specimens
      of human liver, modules were traced through sequential cryosections, and a
      "secondary" module having a height of 1.9 mm, a surface of 14.7 mm(2), and a
      volume of 5.1 mm(3) was reconstructed three-dimensionally. It was subdivided into
      14 "primary" modules by portal tracts and vascular septa and by a common draining
      central venular tree. Primary modules were polyhedral, with seven to nine facets,
      having heights from 0.3 to 0.9 mm, surface areas from 1.7 to 5.0 mm(2), and
      volumes from 0.1 to 0.9 mm(3). Such variation in shape and size is considered an
      important part of the modular organization of the human liver. In conclusion, the
      findings on the three-dimensionality and microcirculation of liver modules
      support and extend the lobular concept and, at the same time, make apparent the
      shortcomings of the concepts of acinar and portal units. The results of this
      study should permit a better interpretation of histological sections of normal
      and pathological liver and provide a basis for understanding the metabolic
      heterogeneity of liver cells and their functional integration into parenchymal
      units.

PMID- 15965927
TI  - How accurate is measuring postvoid residual volume by portable abdominal
      ultrasound equipment in peritoneal dialysis patient?
AB  - INTRODUCTION: Despite the wide spread use of modern portable ultrasound equipment
      to measure the postvoid residual urine, its accuracy and reliability has been
      questioned. We investigated the accuracy of postvoid residual urine measurement
      by portable abdominal ultrasound equipment in end-stage renal disease patients
      who are under either hemodialysis or peritoneal dialysis. MATERIALS AND METHODS:
      A total of 21 male (range: 25-44 years, mean age: 32 years) end-stage renal
      disease patients were studied. Ten were under peritoneal dialysis and 11 under
      hemodialysis. After uroflowmetric study, all patients were evaluated with
      portable abdominal ultrasound equipment (BladderScan BVI 3000, Diagnostic
      Ultrasound Corporation, WA) by both a technician and a physician and they were
      subsequently catheterized with a 10F catheter to measure the residual urine
      volume in the urinary bladder. Postvoid residual urine volume results by portable
      abdominal ultrasound equipment and urethral catheterization were analyzed.
      RESULTS: We found portable abdominal ultrasound to be very accurate to measure
      the volume of postvoid residual urine in hemodialysis patients(r=0.921, P<0.05 by
      physician and r=0.904, P<0.05 by technician). However, accuracy was the worst in
      peritoneal dialysis patients (r=0.055, P=0.88 by physician and r=0.336, P=0.343
      by technician). The technician or physician use of the equipment did not change
      the accuracy profile of the equipment in both hemodialysis and peritoneal
      dialysis patients. CONCLUSIONS: Portable abdominal ultrasound equipment may be an
      unreliable method to measure postvoid residual urine volume in peritoneal
      dialysis patients.

PMID- 15965928
TI  - A critical overview of ESEM applications in the biological field.
AB  - Scanning Electron Microscope (SEM) is a powerful research tool, but since it
      requires high vacuum conditions, the wet materials and biological samples must
      undergo a complex preparation that limits the application of SEM on this kind of
      specimen and often causes the introduction of artifacts. The introduction of
      Environmental Scanning Electron Microscope (ESEM), working in gaseous atmosphere,
      represented a new perspective in biological research. Despite the fact that many
      biological applications have demonstrated the convenience of ESEM, the full
      potentialities of this technology are still under investigation. In this review,
      the exploration of the recent literature data confronted with the first results
      obtained in our experimental work suggest that ESEM represents an important
      extension of conventional scanning microscopy.

PMID- 15965929
TI  - Reconciling the rift: improving clinical psychology graduate training in the
      twenty-first century.
AB  - Most graduate programs in clinical psychology adhere to and reportedly are
      satisfied with the scientist-practitioner model of training. In the present
      commentary, I take the position that this model must be updated to reconcile the
      rift that currently exists between the scientists and the practitioners within
      the field. A return to scientific rigor within the field is espoused, and
      suggestions of ways to improve both undergraduate and graduate curricula are
      made.

PMID- 15965930
TI  - Matrix model of clinical psychology: applause or the sound of one hand clapping?
AB  - The matrix model as proposed by C.R. Snyder and T.R. Elliott (this issue, pp.1033
      1054) is a welcome refocusing of clinical psychology for the 21st century. Yet,
      limitations to the model are that (a) it shifts attention to the target of
      interventions (i.e., "clients") and virtually ignores the function of the
      interventionist; (b) it might not be the best way to characterize "clients"; and
      (c) training might take longer than 5 years. Overall, it is a heuristic model;
      will it be accepted?

PMID- 15965931
TI  - Twenty-first century education: toward greater emphasis on context-social,
      economic, and educational.
AB  - In calling for a greater emphasis on the social, economic, and educational
      contexts, the discussion presented in this article is generally supportive of
      C.R. Snyder and T.R. Elliott's (this issue, pp. 1033-1054) vision of 21st century
      graduate education in clinical psychology. Attention is directed toward the
      asocial nature of professional psychology, a brief analysis of the influence of
      economics on the development of clinical psychology education, and the American
      Psychological Association's accreditation process as it shapes professional
      psychology education.

PMID- 15965932
TI  - New visions and revisions: why isn't graduate education in psychology more
      relevant to professional practice?
AB  - C.R. Snyder and T.R. Elliott (this issue, pp. 1033-1054) propose a four level
      matrix model for graduate education in the 21st century. The model is critically
      reviewed and found to be robust and heuristic. Several critical issues
      confronting training directors in the 21st century that are not acknowledged by
      Snyder and Elliott are identified and discussed.

PMID- 15965933
TI  - The matrix model for clinical psychology: a contextual approach.
AB  - The four level matrix model proposed by C.R. Snyder and T.R. Elliott (this issue,
      PP. 1033-1054) is a bold attempt to provide a coherent philosophy and model to
      guide the training of clinical psychologists. Shortcomings of current training
      practices, such as a focus on individuals rather than community dynamics and on
      pathology rather than strengths, are addressed in the proposed model.
      Difficulties in the implementation of the model are discussed.

PMID- 15965934
TI  - An attachment theory perspective on the proposed matrix model.
AB  - The matrix model (C.R. Snyder & T.R. Elliott, this issue, pp. 1033-1054)
      advocates an increased grounding of clinical psychology graduate students in
      theory. The matrix model is theory-based in the ways that it advances this goal.
      Accordingly, evaluating the matrix model from an extant theoretical perspective
      should shed light on its applicability and utility as an educational framework.
      The present attachment theory perspective on the matrix model demonstrates that
      it meets its stated goals in that it possesses adequate (a) breadth in
      incorporating theory from across subdisciplines in psychology, and (b) depth in
      how it facilitates conceptualizing clients and research participants at the
      intrapersonal, interpersonal, and societal levels. The benefits for incorporating
      the matrix model in clinical psychology graduate programs are discussed.

PMID- 15965935
TI  - Meaning-making and the matrix model: does one size really fit all?
AB  - Despite the multifocal complexity of the matrix model (C.R. Snyder & T.R.
      Elliott, this issue, pp. 1033-1054), its close correspondence with the
      theoretical dialectics and philosophy of clinical constructivism auger well for
      its capacity to articulate with existing approaches to graduate education in
      psychology. In this article points of contact are documented between the two
      approaches, and a caveat is included about the limits of the matrix model in
      ensuring greater relevance of clinical training to the settings in which
      contemporary professionals will work.

PMID- 15965936
TI  - The enduring value of the Boulder model: "upon this rock we will build".
AB  - We comment on the article by C.R. Snyder and T.R. Elliott, "Twenty-First Century
      Graduate Education in Clinical Psychology: A Four Level Matrix Model" (this
      issue, PP. 1033-1054). We agree with many of the specific sentiments expressed by
      these authors but not with their dismissal of the Boulder model. We conclude that
      the Boulder model is as valuable today as when first articulated and that it
      provides a sturdy foundation upon which to make the sorts of changes the authors
      suggest.

PMID- 15965937
TI  - Can a matrix make a training model?: "no." Let's not throw out the Boulder model.
AB  - In response to the call by C.R. Snyder and T.R. Elliott (this issue, pp. 1033
      1054) for a new clinical training program, I propose the need to keep the Boulder
      model. I trace my involvement with the Boulder model from my clinical graduate
      training through my 30 years as a professor. One of the major tasks of clinical
      training is to teach graduate students to think in a critical rigorous fashion in
      order to avoid the fads in the mental health field.

PMID- 15965938
TI  - Clinical training for the next millennium.
AB  - Several issues regarding the matrix model (C.R. Snyder & T.R. Elliott, this
      issue, pp. 1033-1054) are addressed. First is the role that positive psychology
      can play in therapy and prevention training. Next, assumptions of the medical
      model are discussed concerning training students to be competent therapists in an
      era of managed care. Finally, questions are raised about the response of training
      programs to the integration of psychology with biobehavioral approaches to human
      behavior.

PMID- 15965939
TI  - Toward promoting generative cultures of intentional mentoring within academic
      settings.
AB  - Mentoring promotes ongoing learning of clinical psychologists, regardless of
      their expertise and experience. Most academic programs, however, do not possess
      vigorous mentoring cultures in which mentors simultaneously are learners.
      Academic programs are largely based on "mastery" philosophies that tacitly aim
      mentoring at less-experienced peers. This orientation can make stigmatizing
      mentoring opportunities, especially for psychologists from underrepresented
      populations. Using concepts from experiential learning theory, we articulate
      interventions to invigorate mentoring cultures and make mentoring less
      stigmatizing.

PMID- 15965940
TI  - A team effort: reply to Snyder and Elliott.
AB  - This response to C.R. Snyder and T.R. Elliott's innovative proposals for training
      (this issue, pp. 1033-1054) highlights areas of agreement with the authors as
      well as encourages greater attention to several issues. These include counseling
      psychology and its historical emphasis on wellness, mentoring training for
      current faculty as well as graduate students, and appreciation for the diverse
      areas within psychology as well as within the broader social sciences (e.g.,
      social work, marriage and family therapy) as contributors to such training.

PMID- 15965941
TI  - Quantitative studies of autonomic function.
AB  - Dysfunction of the peripheral and central autonomic nervous system is common in
      many neurological and general medical diseases. The quantitative assessment of
      sympathetic and parasympathetic function is essential to confirm the diagnosis of
      autonomic failure, to provide the basis for follow-up examinations, and
      potentially to monitor successful treatment. Various procedures have been
      described as useful tools to quantify autonomic dysfunction. The most important
      tests evaluate cardiovascular and sudomotor autonomic function. In this review,
      we therefore focus on standard tests of cardiovascular and sudomotor function
      such as heart-rate variability at rest and during deep breathing, active
      standing, and the Valsalva maneuver, and on the sympathetic skin response. These
      tests are widely used for routine clinical evaluation in patients with peripheral
      neuropathies. Refined methods of studying heart-rate variability, baroreflex
      testing, and detailed measures of sweat output are mostly used for research
      purposes. In this context, we describe the spectral analysis of slow modulation
      of heart rate or blood pressure, reflecting sympathetic and parasympathetic
      influences, and consider various approaches to baroreflex testing, the
      thermoregulatory sweat test, and the quantitative sudomotor axon reflex test.
      Finally, we discuss microneurography as a technique of direct recording of muscle
      sympathetic nerve activity.

PMID- 15965942
TI  - Following the money: economic inhibitors of change affecting graduate education
      in clinical psychology.
AB  - C.R. Snyder and T.R. Elliott (this issue, pp. 1033-1054) offer a thoughtful and
      elaborate model for future training in graduate clinical psychology, couched in
      visionary optimism. However, they interpret history and present trends in a
      manner that seems to ignore the realistic demands of economic forces. They
      propose thoughtful, constructive, pro-social directions, but seem at least
      partially oblivious to underlying economic forces destined to impede meaningful
      implementation of their model.

PMID- 15965943
TI  - The end of clinical psychology as we know it? A response to Snyder and Elliott's
      four level matrix model.
AB  - C.R. Snyder and T.R. Elliott's proposed model (this issue, pp. 1033-1054)
      represents a good effort toward reexamining the premises of clinical psychology
      education. However, there are several concepts left underdeveloped and
      inadequately defined. Furthermore, their ideas for improving clinical training
      seem largely divorced from the model proposed. Before making propositions toward
      a "new clinical psychology," clarification of the constructs and model is needed
      to understand how it can better educate and prepare future clinical psychologists
      for the demands of tomorrow's marketplaces.

PMID- 15965944
TI  - Constructive suggestions for the practical education of professional life
      counselors.
AB  - Professional life counselors will serve an increasingly important role in the
      life quality of global citizens in the 21st century. The optimal preparation of
      service providers will reflect basic principles of human development,
      professional helping, and educational processes. The dynamic systems
      appreciations of constructivism offer valuable scaffoldings for mentoring and
      apprenticeship in human helping. Suggestions are made for practical refinements
      in professional education.

PMID- 15965945
TI  - The return of science to education in clinical psychology: a reply to Snyder and
      Elliott.
AB  - Clinical psychology currently exists in a state of isolation from the other
      scientific domains. This disconnect is explained, in part, by the continued
      adherence to mind-body dualism by many clinical psychologists and the rift
      between researchers and practitioners within the discipline. However, natural
      science researchers are reasserting the connection between physical and
      biological properties and psychological phenomena. As a result, knowledge and
      skill pertaining to the scientific method will become increasingly important in
      the education of future clinical psychologists. Modifications to both
      undergraduate and graduate training are suggested.

PMID- 15965946
TI  - Re-envisioning the training and practice of clinical psychologists: preserving
      science and research orientations in the face of change.
AB  - We argue for preservation of an expectation of psychologists that approach human
      problems from an evidence-based perspective. Acquisition of the requisite
      knowledge, skills, and practical experience require access to resources outside
      of graduate psychology programs. Whether adhering to a scientist-practitioner or
      practitioner-scholar model, psychologists must be "scientifically literate."
      Deficiencies are noted in the training of scientist-practitioner psychologists
      for the conduct of clinical trials and the dissemination and sustained
      implementation of evidence-based interventions.

PMID- 15965947
TI  - Sharing open secrets in training future generations of clinical psychologists.
AB  - Commentary writers vary in their agreement with the ideas presented in the C.R.
      Snyder and T.R. Elliott lead article (this issue, PP. 1033-1054), but they share
      the view that clinical-counseling psychology already is in the midst of an
      evolution. There are two general camps to such commentaries. First, there are
      those who caution us to move slowly and carefully as we respond to the change
      inducing forces. Second, there are those who see this time as one in which we
      should make bold moves in our field in response to the societal forces that we
      are encountering. We suggest that the lightning rod for potential changes in the
      field of clinical-counseling psychology must be a shared emphasis on our
      scientific heritage.

PMID- 15965948
TI  - Twenty-first century graduate education in clinical psychology: a four level
      matrix model.
AB  - Clinical psychology is positioned to play key roles in mental and physical health
      issues of 21st century America. In this regard, however, the present Boulder
      model of educating clinical psychologists is not preparing our graduates to meet
      the diverse demands of either today's or tomorrow's marketplaces. Accordingly, we
      introduce a new, four level "matrix model" for the education of future clinical
      psychologists. The core focus of the proposed matrix model is on the weaknesses
      and strengths of people in their personalities and their environments. Moreover,
      this matrix model operates at the individual, interpersonal, institutional, and
      societal-community levels of analyses. The details and implications of this
      proposed educational curriculum are described.

PMID- 15965949
TI  - Progesterone primes zona pellucida-induced activation of phospholipase A2 during
      acrosomal exocytosis in guinea pig spermatozoa.
AB  - We investigated, using guinea-pig spermatozoa as a model, whether phospholipase
      A2 (PLA2) is involved in progesterone or zona pellucida (ZP)-stimulated acrosomal
      exocytosis, if progesterone enhances ZP-induced activation of PLA2, and
      mechanisms underlying PLA2 regulation. Spermatozoa were capacitated and labeled
      in low Ca2+ medium with [14C]choline chloride or [14C]arachidonic acid, washed,
      and then exposed to millimolar Ca2+ and progesterone and/or ZP. Each agonist
      stimulated decrease of phosphatidylcholine (PC) and release of arachidonic acid
      and lysoPC, indicative of PLA2 activation. Aristolochic acid (a PLA2 inhibitor)
      abrogated lipid changes and exocytosis, indicating that these lipid changes are
      essential for exocytosis. Exposure of spermatozoa to submaximal concentrations of
      both progesterone and ZP resulted in a synergistic increase of arachidonic acid
      and lysoPC releases, and exocytosis, suggesting that, under natural conditions,
      both agonists interact to bring about acrosomal exocytosis. Progesterone-induced
      PLA2 activation appears to be mediated by a GABA(A)-like receptor, because
      bicuculline (a GABA(A) receptor antagonist) blocked arachidonic acid release and
      exocytosis. In agreement with this, GABA mimicked progesterone actions. ZP
      induced activation of PLA2 seemed to be transduced via G(i) proteins because
      pertussis toxin blocked arachidonic acid release and acrosomal exocytosis. PLA2
      may be regulated by PKC because progesterone- or ZP-induced release of
      arachidonic acid was blocked by the PKC inhibitors staurosporine or chelerythrine
      chloride. PLA2 could also be regulated by the cAMP-PKA pathway; inclusion of the
      PKA inhibitor 14-22 amide or H-89 led to a reduction in arachidonic acid release
      or exocytosis after progesterone or ZP. Taken together, these results suggest
      that PLA2 plays an essential role in progesterone or ZP-stimulated exocytosis
      with progesterone priming ZP action.

PMID- 15965950
TI  - Brg1, the ATPase subunit of the SWI/SNF chromatin remodeling complex, is required
      for myeloid differentiation to granulocytes.
AB  - Many mammalian SWI/SNF complexes use Brahma-related gene 1 (Brg1) as a catalytic
      subunit to remodel nucleosomes for transcription regulation. In several
      mesenchymal cells and tissues, expression of a defective Brg1 protein negates the
      normal activity of the SWI/SNF complex and delays or blocks differentiation. To
      investigate the role of SWI/SNF complexes during myelopoiesis, we stably
      expressed a dominant negative (dn) Brg1 mutant in the myeloid lineage. Forced
      expression of dnBrg1 in IL-3-dependent murine 32Dcl3 myeloid progenitor cells
      results in a profound delay in the granulocyte-colony stimulating factor (G-CSF)
      induced granulocytic maturation. These cells also exhibit a significant decrease
      in the expression of both CD11b and Gr-1 surface receptors, which are normally
      upregulated during granulopoiesis, and show sustained expression of
      myeloperoxidase, which is synthesized primarily during the promyelocytic (blast)
      stage of myeloid development. Thus, dnBrg1 expression causes a developmental
      block at the promyelocytic/metamyelocytic stage of myeloid differentiation. Our
      findings indicate that the normal chromatin remodeling function of Brg1 is
      necessary for the G-CSF dependent differentiation of myeloid cells towards the
      granulocytic lineage. This dependency on Brg1 may reflect a stringent requirement
      for chromatin remodeling at a critical stage of hematopoietic cell maturation.

PMID- 15965951
TI  - Subcellular distribution of calcium-sensitive potassium channels (IK1) in
      migrating cells.
AB  - Cell migration is crucial for wound healing, immune defense, or formation of
      tumor metastases. In addition to the cytoskeleton, Ca2+ sensitive K+ channels
      (IK1) are also part of the cellular "migration machinery." We showed that Ca2+
      sensitive K+ channels support the retraction of the rear part of migrating MDCK-F
      cells by inducing a localized shrinkage at this cell pole. So far the molecular
      nature and in particular the subcellular distribution of these channels in MDCK-F
      cells is unknown. We compared the effect of IK1 channel blockers and activators
      on the current of a cloned IK1 channel from MDCK-F cells (cIK1) and the migratory
      behavior of these cells. Using IK1 channels labeled with a HA-tag or the enhanced
      green fluorescent protein we studied the subcellular distribution of the canine
      (cIK1) and the human (hIK1) channel protein in different migrating cells. The
      functional impact of cIK1 channel activity at the front or rear part of MDCK-F
      cells was assessed with a local superfusion technique and a detailed morphometric
      analysis. We show that it is cIK1 whose activity is required for migration of
      MDCK-F cells. IK1 channels are found in the entire plasma membrane, but they are
      concentrated at the cell front. This is in part due to membrane ruffling at this
      cell pole. However, there appears to be only little cIK1 channel activity at the
      front of MDCK-F cells. In our view this apparent discrepancy can be explained by
      differential regulation of IK1 channels at the front and rear part of migrating
      cells.

PMID- 15965952
TI  - CXCL12 (SDF-1) and CXCL13 (BCA-1) chemokines significantly induce proliferation
      and collagen type I expression in osteoblasts from osteoarthritis patients.
AB  - To evaluate the role of CXC chemokines CXCL8 (IL8), CXCL10 (IP-10), CXCL12 (SDF
      1), and CXCL13 (BCA-1) in bone remodeling, we analyzed their effects on
      osteoblasts (OBs) obtained from subchondral trabecular bone tissue of
      osteoarthritis (OA) and post-traumatic (PT) patients. The expression of CXC
      receptors/ligands (CXCR1/CXCL8, CXCR2/CXCL8, CXCR3/CXCL10, CXCR4/CXCL12, and
      CXCR5/CXCL13) was analyzed in cultured OBs by flow cytometry and
      immunocytochemistry. Functional assays on CXC chemokine-treated-OBs in the
      presence or absence of their specific inhibitors were performed to analyze
      cellular proliferation and the enzymatic response to chemokine activation. The
      expression of chemokine ligands/receptors was also confirmed in bone tissue
      samples by immunohistochemical analysis. Collagen type I and alkaline phosphatase
      mRNA expression were analyzed on CXCL12- and CXCL13-treated OBs by real-time PCR.
      OBs from both OA and PT patients expressed high levels of CXCR3 and CXCR5 and
      lower amounts of CXCR1 and CXCR4. CXCL12 and CXCL13, only in OBs from OA
      patients, induced a significant proliferation that was also confirmed by specific
      blocking experiments. Moreover, OBs from OA patients released a higher amount of
      CXCL13 than those of PT patients while no differences were found for CXCL12. In
      the remodeling area of bone tissue samples, immunohistochemical analysis
      confirmed that OBs expressed CXCL12/CXCR4 and CXCL13/CXCR5 both in OA and PT
      samples. CXCL12 and CXCL13 upregulated collagen type I mRNA expression in OBs
      from OA patients. These data suggest that CXCL12 and CXCL13 may directly modulate
      cellular proliferation and collagen type I in OA patients, so contributing to the
      remodeling process that occurs in the evolution of this disease.

PMID- 15965953
TI  - Characterization of liver function in transdifferentiated hepatocytes.
AB  - We previously demonstrated that dexamethasone (Dex) induces the
      transdifferentiation (or conversion) of the pancreatic progenitor cell line AR42J
      B13 (B13) to hepatocytes based on the expression of liver proteins. We have
      extended our original observations to determine: (1) the effects of Dex on
      pancreatic gene expression; (2) the time course of expression of liver enriched
      transcription factors during conversion from pancreatic to hepatic phenotype; (3)
      the functional potential of transdifferentiated hepatocytes; (4) the
      proliferative capacity of transdifferentiated hepatocytes; and (5) whether
      ectopic expression of transcription factors can induce the hepatic phenotype in
      pancreatic B13 cells. The results were as follows. The B13 cell markers amylase,
      synaptophysin, and neurofilament were lost in transdifferentiated hepatocytes
      compared to control cells and the liver enriched transcription factors C/EBPbeta
      and C/EBPalpha were induced first, followed by HNF4alpha and then RXRalpha. Using
      RT-PCR analysis and immunolocalisation studies, we detected hepatic markers
      (e.g., apolipoprotein B) in Dex-treated cells. In transdifferentiated hepatocytes
      albumin was secreted, insulin stimulated lipid deposition and ciprofibrate
      enhanced the expression of catalase. Proliferation of transdifferentiated
      hepatocytes is promoted in the presence of HGF and NEAA as indicated by the co
      expression of the cell cycle markers cyclin D and phosphohistone H3 with liver
      proteins. Lastly, ectopic expression of C/EBPalpha or C/EBPbeta in AR42J-B13
      cells was sufficient to induce transdifferentiation, based on nuclear
      localization of HNF4alpha and induction of UDP-glucuronosyltransferase
      expression. These results indicate that the B13 progenitor cell model is suitable
      for studying liver function and for understanding the molecular and cellular
      events that occur during transdifferentiation.

PMID- 15965954
TI  - Habitual snoring and blood pressure.

PMID- 15965955
TI  - Early pulmonary involvement in Niemann-Pick type B disease: lung lavage is not
      useful.
AB  - Niemann-Pick disease (NPD) is a rare, autosomal-recessively inherited lipid
      storage disease which is characterized by intracellular deposition of
      sphingomyelin in various body tissues. The disease is heterogeneous and
      classified into six groups. Pulmonary parenchymal involvement may be a feature of
      several subtypes of NPD, including type B. Progressive pulmonary involvement in
      NPD type B is a major cause of morbidity and mortality. It is usually diagnosed
      at older ages. Only a few cases with early pulmonary involvement have been
      reported. In this report, a patient with NPD type B, hospitalized with the
      diagnosis of pneumonia at age 3 months, is presented. Following treatment for
      pneumonia, she continued to have persistent respiratory symptoms and became
      oxygen-dependent. High-resolution computed tomography of the chest revealed
      diffuse interstitial changes. During follow-up, the patient developed
      hepatosplenomegaly. Lung, liver, and bone marrow biopsies showed characteristic
      findings for NPD. Biochemical studies also confirmed the diagnosis, and the
      sphingomyelinase enzyme level of the patient was low. Unilateral lung lavage was
      performed in order to decrease lipid storage as a treatment modality. However,
      there was no clinical or radiological improvement. The patient died at age 15
      months due to progressive respiratory failure. Pulmonary involvement is a rare
      entity in early childhood in patients with NPD type B, but should be considered
      in the differential diagnosis of persistent interstitial lung disease. It may
      cause progressive respiratory failure, but the treatment options remain limited.

PMID- 15965956
TI  - Unusual cause of lung and renal disease in a baby with trisomy 21.
AB  - We describe a case of right thoracic ectopic kidney in a 13-month-old boy with
      trisomy 21. We think an intrathoracic kidney should be considered in the
      differential diagnosis of a thoracic mass.

PMID- 15965958
TI  - Effects of different types of oxidative stress in RPE cells.
AB  - Oxidative damage to retinal pigmented epithelial (RPE) cells and photoreceptors
      has been implicated in the pathogenesis of age-related macular degeneration
      (AMD). In order to develop new treatments, it is necessary to characterize the
      antioxidant defense system in RPE cells to better define their vulnerabilities
      and how they can be remedied. In this study, we sought to investigate the effects
      of three different types of oxidative stress on cultured RPE cells. Carbonyl
      content in RPE cells increased with increasing concentrations of oxidants or
      increasing duration of exposure with high reproducibility, validating ELISA for
      carbonyl content as a valuable quantitative measure of oxidative damage. Compared
      to other cell types, RPE cells were able to survive exposure to H2O2 quite well
      and exposure to paraquat extremely well. Comparison of the total amount of
      oxidative damage at the IC50 for each type of stress showed a rank order of
      hyperoxia > paraquat > H2O2, and since these stressors primarily target different
      cellular compartments, it suggests that the endogenous defense system against
      oxidative damage in RPE cells protects well against damage to mitochondria and
      endoplasmic reticulum, and is less able to handle oxidative damage at the cell
      surface. Supplementation of media with ascorbic acid provided significant
      protection from H2O2-induced oxidative damage, but not that induced by paraquat
      or hyperoxia. Supplementation with docosahexaenoic acid or alpha-tocopherol
      significantly reduced oxidative damage from H2O2 or hyperoxia, but not that
      induced by paraquat. We conclude that exposure to different types of oxidative
      stress results in different patterns of accrual of oxidative damage to proteins
      in RPE cells, different patterns of loss of viability, and is differentially
      countered by antioxidants. This study suggests that multiple types of oxidant
      stress should be used to probe the vulnerabilities of the retina and RPE in vivo,
      and that ELISA for carbonyl content provides a valuable tool for quantitative
      assessment of oxidative damage for such studies.

PMID- 15965959
TI  - Endogenous hemichannels play a role in the release of ATP from Xenopus oocytes.
AB  - ATP is an electrically charged molecule that functions both in the supply of
      energy necessary for cellular activity and as an intercellular signaling
      molecule. Although controlled ATP secretion occurs via exocytosis of granules and
      vesicles, in some cells, and under certain conditions, other mechanisms control
      ATP release. Gap junctions, intercellular channels formed by connexins that link
      the cytoplasm of two adjacent cells, control the passage of ions and molecules up
      to 1 kDa. The channel is formed by two moieties called hemichannels, or
      connexons, and it has been suggested that these may represent an alternative
      pathway for ATP release. We have investigated the release of ATP through
      hemichannels from Xenopus oocytes that are formed by Connexin 38 (Cx38), an
      endogenous, specific type of connexin. These hemichannels generate an inward
      current that is reversibly activated by calcium-free solution and inhibited by
      octanol and flufenamic acid. This calcium-sensitive current depends on Cx38
      expression: it is decreased in oocytes injected with an antisense oligonucleotide
      against Cx38 mRNA (ASCx38) and is increased in oocytes overexpressing Cx38.
      Moreover, the activation of these endogenous connexons also allows transfer of
      Lucifer Yellow. We have found that the release of ATP is coincident with the
      opening of hemichannels: it is calcium-sensitive, is inhibited by octanol and
      flufenamic acid, is inhibited in ASCx38 injected oocytes, and is increased by
      overexpression of Cx38. Taken together, our results suggest that ATP is released
      through activated hemichannels in Xenopus oocytes.

PMID- 15965960
TI  - Proceedings of the fourth National Congress of the Italian Society of Virology.
AB  - The aim of the yearly National Congress of the Italian Society of Virology (SIV)
      is to promote the discussion between senior and younger researchers to improve
      the knowledge and scientific collaboration among the various areas of Virology.
      The invited and selected lecturers of the fourth National Congress of SIV covered
      the following topics: general Virology and viral Genetics; virus host
      interactions and pathogenesis; viral immunology and vaccines; emerging and re
      emerging viral diseases; antiviral therapy; innovative diagnostics; viral
      biotechnologies and gene therapy. As in the previous edition (Salata and Palu,
      2004 J Cell Physiol 199:171-173), a specific topic was thoroughly covered in a
      roundtable. In this edition the overviewed topic was HCV, from epidemiology and
      genetic variability to immunology and antiviral therapy. The final program can be
      found at the web site http://www.siv-virologia.it. A summary of the oral
      presentations of the 2004 meeting is reported.

PMID- 15965961
TI  - Novel expression of liver FBPase in Langerhans islets of human and rat pancreas.
AB  - Several reports have indicated the absence of gluconeogenic enzymes in pancreatic
      islet cells. In contrast, here we demonstrate that liver fructose-1,6
      bisphosphatase (FBPase) is highly expressed both in human and rat pancreas.
      Interestingly, pancreatic FBPase is active and functional, and is inhibited by
      AMP and fructose-2,6-bisphosphate (Fru-2,6-P2). These results suggest that FBPase
      may participate as a component of a metabolic sensing mechanism present in the
      pancreas. Immunolocalization analysis showed that FBPase is expressed both in
      human and rat Langerhans islets, specifically in beta cells. In humans, FBPase
      was also located in the canaliculus and acinar cells. These results indicate that
      FBPase coupled with phosphofructokinase (PFK) plays a crucial role in the
      metabolism of pancreatic islet cells. The demonstration of gluconeogenic
      recycling of trioses as a new metabolic signaling pathway may contribute to our
      understanding of the differences between the insulin secretagogues trioses,
      fructose, and glucose in pancreas.

PMID- 15965962
TI  - Alkaline induces metallothionein gene expression and potentiates cell
      proliferation in Chinese hamster ovary cells.
AB  - Metallothionein (MT) gene expression is increased in cadmium resistant Chinese
      hamster ovary cells (CHO Cd(R)) upon medium (regular or serum-free) change during
      culturing. Among the major components of the medium, NaHCO3 was found to be able
      to induce MT gene expression in a dose- and time-dependent manner. The same
      effect was observed with other alkaline solutions, such as HEPES and NaOH. Using
      MT promoter-luciferase reporter gene constructs, we found that the presence of
      metal response elements (MREs) in the promoter region is necessary for NaHCO3
      induced MT gene transcription. This finding is further supported by the
      observation that the binding activity between the metal-responsive transcription
      factor 1 (MTF-1) and the MRE were increased after NaHCO3 treatment. Following
      NaHCO3 treatment, an increase in cell proliferation was observed in CdR cells but
      not in the parental CHO K1 cells that do not express MT transcripts due to MT
      gene methylation. Using synchronized cells, an increase in cell proliferation was
      observed 9 h after NaHCO3 addition. Notably, proliferation of CHO K1 cells was
      increased when transfected with an MT gene. The effect of MT on cell growth was
      affirmed by treating CHO K1 cells with 5-azacytidine (Aza) to demethylate the MT
      gene. Proliferation increased in Aza-treated CHO K1 cells after NaHCO3 treatment.
      These results demonstrate that NaHCO3 stimulates MT gene expression and causes an
      enhancement of cell proliferation in CHO cells.

PMID- 15965963
TI  - Role of cell-cycle regulators in lung cancer.
AB  - Lung cancer is the leading cause of cancer death worldwide. Histologically, 80%
      of lung cancers are classified as non-small-cell lung cancer (NSCLC), and the
      remaining 20% as small-cell lung cancer (SCLC). Lung carcinoma is the result of
      molecular changes in the cell, resulting in the deregulation of pathways
      controlling normal cellular growth, differentiation, and apoptosis. This review
      summarizes some of the most recent findings about the role of cell-cycle proteins
      in lung cancer pathogenesis and progression.

PMID- 15965964
TI  - Inhibition of human embryonic stem cell differentiation by mechanical strain.
AB  - Mechanical forces have been reported to induce proliferation and/or
      differentiation in many cell types, but the role of mechanotransduction during
      embryonic stem cell fate decisions is unknown. To ascertain the role of
      mechanical strain in human embryonic stem cell (hESC) differentiation, we
      measured the rate of hESC differentiation in the presence and absence of biaxial
      cyclic strain. Above a threshold of 10% cyclic strain, applied to a deformable
      elastic substratum upon which the hESC colonies were cultured, hESC
      differentiation was reduced and self-renewal was promoted without selecting
      against survival of differentiated or undifferentiated cells. Frequency of
      mechanical strain application had little effect on extent of differentiation.
      hESCs cultured under cyclic strain retained pluripotency, evidenced by their
      ability to differentiate to cell lineages in all three germ layers. Mechanical
      inhibition of hESC differentiation could not be traced to secretion of chemical
      factors into the media suggesting that mechanical forces may directly regulate
      hESC differentiation. Mechanical strain is not sufficient to inhibit
      differentiation, however, in unconditioned medium, hESCs grown under strain
      differentiated at the same rate as cells cultured in the absence of strain. Thus,
      while mechanical forces play a role in regulating hESC self-renewal and
      differentiation, they must act synergistically with chemical signals. These
      findings imply that application of mechanical forces may be useful, in
      combination with chemical and matrix-encoded signals, towards controlling
      differentiation of hESCs for therapeutic applications.

PMID- 15965965
TI  - Ultrastructural defects of collagen VI filaments in an Ullrich syndrome patient
      with loss of the alpha3(VI) N10-N7 domains.
AB  - Ultrastructural alterations of collagen VI in cultured fibroblasts and reduced
      collagen VI immunostaining in the papillary dermis and endomysium were detected
      in a patient with a mild form of Ullrich congenital muscular dystrophy caused by
      a COL6A3 gene mutation. The patient had been previously demonstrated to express
      an alpha3(VI) chain shorter than normal due to skipping of the mutated exon. We
      show that collagen VI filaments are not organized in a normal network in the
      extracellular matrix secreted by patient's cultured fibroblasts. Moreover, we
      demonstrate that in this patient the alpha3(VI) chain is produced in lower
      amounts and it is almost exclusively represented by the shorter, alternatively
      spliced N6-C5 isoform. These results suggest that different alpha3(VI) chain
      isoforms, containing also domains of the N10-N7 region, are required for
      assembling a proper collagen VI network in the extracellular matrix.

PMID- 15965966
TI  - A high predisposition to depression and anxiety in mothers and other matrilineal
      relatives of children with presumed maternally inherited mitochondrial disorders.
AB  - Although mothers of chronically ill children are generally prone to depression
      and anxiety, clinical observation suggests that these symptoms are relatively
      increased in mothers of children with maternally inherited mitochondrial
      disorders (MIMD). In this study, the Beck Depression Inventory II (BDI), the Beck
      Anxiety Inventory (BAI), and a non-standardized mental health questionnaire were
      administered to 15 mothers of children with MIMD and 17 mothers of children with
      autosomal recessive metabolic disorders (ARMD) followed in one clinic. One half
      of the children in both groups suffer from mental retardation and/or > or = 2
      hospitalizations/year related to their genetic disorder, and were labeled as
      severely affected. BDI and BAI scores were similar between mothers of severely
      affected MIMD and ARMD children, but BDI and BAI scores were threefold higher in
      mothers of mildly affected MIMD versus ARMD children (P = 0.001 and P = 0.003,
      respectively). Any mental health condition was self-reported in 10/15 MIMD and
      2/17 ARMD mothers (P = 0.002), while at least one mental health condition per
      family was reported to be present in a matrilineal first-degree relative of the
      mother in 8/15 MIMD versus 1/17 ARMD families (P = 0.004). Our data confirm that
      mental health conditions, particularly depression, are diagnosed at an increased
      frequency among matrilineal relatives likely sharing the same mitochondrial DNA
      (mtDNA) as the affected proband. While previous studies have demonstrated that
      mtDNA sequences can affect brain function, our data suggests that in addition
      mtDNA sequences can predispose individuals towards the development of some
      "mental health" disorders. Thus, "genome-wide" studies to screen for genes
      associated with depression and anxiety should not neglect the small, yet
      important, mitochondrial genome.

PMID- 15965967
TI  - Functional COMT variant predicts response to high dose pyridoxine in Parkinson's
      disease.
AB  - Pyridoxal-5-phosphate, the biological active form of pyridoxine, is a cofactor
      for dopa-decarboxylase (DDC) enzyme. Pyridoxine may augment the conversion of
      levodopa to dopamine in the periphery and therefore decrease availability of
      levodopa to the brain. However, this effect can be negated in the presence of a
      DDC inhibitor, which potentiates plasma levodopa level. A single nucleotide
      polymorphism at the nucleotide 1947 in the catechol-O-methyltransferase (COMT)
      gene encodes the high (COMT(H)) and low activity (COMT(L)) forms of the enzyme.
      In this study, we examined the effect of the COMT(L) allele on the clinical
      response to pyridoxine in Parkinson's disease (PD) patients. PD patients who were
      on stable and optimized dose of levodopa were included in this study. Their mean
      motor and activities of living score improved after high dose pyridoxine (P =
      0.09, P = 0.04), and worsened after a washout period (P = 0.005, P = 0.001).
      Using a multivariate model, the presence of the COMT(L) allele predicted response
      to pyridoxine, with the best outcome observed in COMT(L/L) homozygotes. Our
      observational study suggests that the status the functional COMT(L) variant may
      be potentially useful to select PD patients for high dose pyridoxine therapy.

PMID- 15965968
TI  - Population-based and family-based association study of 5'UTR polymorphism of the
      reelin gene and schizophrenia.
AB  - Reelin is a glycoprotein involved in the migration and positioning of
      proliferating neurons and synaptic connectivity during neurodevelopment. It may
      also modulate neuronal plasticity throughout life. Therefore, the reelin gene is
      a candidate gene for schizophrenia. We examined the association of the CGG repeat
      polymorphism in the 5'-untranslated region of the reelin gene with schizophrenia
      in 266 unrelated French Caucasian patients, 156 of their parents, and 103
      controls. We found no difference in the allele distribution between patients and
      controls although there was a significant higher prevalence of the genotype 8-8
      in controls (CLUMP T3: chi(2) = 6.3, P = 0.035). There was no significant
      transmission disequilibrium in intrafamilial analysis. To refine our phenotypic
      characterization and in accordance with converging evidence suggesting that
      treatment resistance is associated with indices of abnormal neurodevelopment, we
      studied the association between reelin gene polymorphism and response to
      antipsychotics. Patients who responded to antipsychotics had a higher frequency
      of both the (CGG)(10) allele and (CGG)(10)-containing genotypes (P = 0.02; P =
      0.006, respectively), with an odd ratio for genotypes of 4.2 (CI = [1.4;12.4]).
      Our results weakly support an association of reelin gene variants with
      schizophrenia as a whole, yet suggest that reelin could be associated with
      treatment-resistant schizophrenia.

PMID- 15965969
TI  - Evidence for a common biological basis of the Absorption trait, hallucinogen
      effects, and positive symptoms: epistasis between 5-HT2a and COMT polymorphisms.
AB  - Absorption represents a disposition to experience altered states of consciousness
      characterized by intensively focused attention. It is correlated with hypnotic
      susceptibility and includes phenomena ranging from vivid perceptions and
      imaginations to mystical experiences. Based on the assumption that drug-induced
      and naturally occurring mystical experiences share common neural mechanisms, we
      hypothesized that Absorption is influenced by the T102C polymorphism affecting
      the 5-HT2a receptor, which is known to be an important target site of
      hallucinogens like LSD. Based on the pivotal role ascribed to the prefrontal
      executive control network for absorbed attention and positive symptoms in
      schizophrenia, it was further hypothesized that Absorption is associated with the
      VAL158MET polymorphism of the catechol-O-methyltransferase (COMT) gene affecting
      the dopaminergic neurotransmitter system. The Tellegen Absorption Scale was
      administered to 336 subjects (95 male, 241 female). Statistical analysis revealed
      that the group with the T/T genotype of the T102C polymorphism, implying a
      stronger binding potential of the 5-HT2a receptor, indeed had significantly
      higher Absorption scores (F = 10.00, P = 0.002), while no main effect was found
      for the COMT polymorphism. However, the interaction between T102C and COMT
      genotypes yielded significance (F = 3.89; P = 0.049), underlining the known
      functional interaction between the 5-HT and the dopaminergic system. These
      findings point to biological foundations of the personality trait of Absorption.

PMID- 15965970
TI  - Multistate active spaces from local CAS-SCF molecular orbitals: the
      photodissociation of HFCO as an example.
AB  - A recently developed algorithm to generate localized molecular orbitals (LMO) is
      applied to the study of excited states along a photodissociation process. The
      LMOs allow for the selection of a consistent complete active space (CAS) for the
      simultaneous description of all the electronic states involved in a multistate
      process on the basis of simple chemical criteria. The local nature of the
      orbitals is used to label them in a unique way that does not depend on the
      molecular geometry. The selection of the electronic configurations of interest
      for the set of target states on only the basis of the dominant excitations
      required by the simplest configuration interaction (CI) descriptions for both
      ground and excited states is fairly simplified. The following of the changes in
      the nature of the states along cuts in the set of potential energy surfaces (PES)
      is also simpler. The C--F bond breaking and the states involved in the
      photodissociation of the HFCO system, together with another geometrical path
      along the PES of the same previous states, are studied by way of examples in this
      work. The local nature of the MOs warrants that this small system is
      representative enough to show the advantages of the procedure and that its
      application to larger systems (R-FCO systems) would be straightforward.

PMID- 15965971
TI  - Lennard-Jones parameters for the combined QM/MM method using the B3LYP/6
      31G*/AMBER potential.
AB  - A combined DFT quantum mechanical and AMBER molecular mechanical potential
      (QM/MM) is presented for use in molecular modeling and molecular simulations of
      large biological systems. In our approach we evaluate Lennard-Jones parameters
      describing the interaction between the quantum mechanical (QM) part of a system,
      which is described at the B3LYP/6-31+G* level of theory, and the molecular
      mechanical (MM) part of the system, described by the AMBER force field. The
      Lennard-Jones parameters for this potential are obtained by calculating hydrogen
      bond energies and hydrogen bond geometries for a large set of bimolecular
      systems, in which one hydrogen bond monomer is described quantum mechanically and
      the other is treated molecular mechanically. We have investigated more than 100
      different bimolecular systems, finding very good agreement between hydrogen bond
      energies and geometries obtained from the combined QM/MM calculations and results
      obtained at the QM level of theory, especially with respect to geometry.
      Therefore, based on the Lennard-Jones parameters obtained in our study, we
      anticipate that the B3LYP/6-31+G*/AMBER potential will be a precise tool to
      explore intermolecular interactions inside a protein environment.

PMID- 15965972
TI  - Substituent effects on heats of formation, group interactions, and detonation
      properties of polyazidocubanes.
AB  - We have calculated the heats of formation (HOFs) for a series of polyazidocubanes
      by using the density functional theory (DFT), Hartree-Fock, and MP2 methods with
      6-31G* basis set as well as semiempirical methods. The cubane skeleton was chosen
      for a reference compound, that is, the cubane skeleton was not broken in the
      process of designing isodesmic reactions. There exists group additivity for the
      HOF with respect to the azido group. The semiempirical AM1 method also produced
      reliable results for the HOFs of the title compounds, but the semiempirical
      MINDO3 did not. The relationship between HOFs and molecular structures was
      discussed. It was found that the HOF increases 330-360 kJ/mol for each additional
      number of the azido group being added to the cubane skeleton. The distance
      between azido groups slightly influences the values of HOFs. The interacting
      energies of neighbor azido groups in polyazidocubanes are in the range of 2.3
      approximately 6.6 kJ/mol, which are so small and less related to the substituent
      numbers. The average interaction energy between nearest neighbor --N3 groups in
      the most stable conformer of octaazidocubane is 2.29 kJ/mol at the B3LYP/6-31G*
      level. The relative stability related to the number of azido groups of the title
      compounds was assessed based on the calculated HOFs, the energy gaps between the
      frontier orbitals, and the bond orders of the C--N3 and C--C bonds. The predicted
      detonation velocity of hepta- and octa-derivatives is over 9 km/s, and the
      detonation pressure of them is ca. 40 GPa or over.

PMID- 15965973
TI  - Smith-Lemli-Opitz syndrome in trisomy 13: how does the mix work?
AB  - BACKGROUND: Trisomy 13 and Smith-Lemli-Opitz syndrome (SLOS) are both well
      recognized multiple congenital anomaly/mental retardation syndromes. CASE: In
      this report we describe a male newborn with trisomy 13 who also has features of
      SLOS, such as 2/3 toe syndactyly and a shawl-like scrotum. Biochemical analysis
      was consistent with SLOS, and limited molecular analysis revealed 1 mutation in
      the DHCR7 gene. CONCLUSIONS: The challenges in establishing the diagnosis of SLOS
      in this patient are presented and the unique coexistence of the 2 major
      malformation syndromes is discussed. Given the overlapping phenotype of the 2
      syndromes, our report should encourage further research on cholesterol
      biosynthesis in patients with trisomy 13.

PMID- 15965974
TI  - Teratogenic effects of bis-diamine on the developing cardiac conduction system.
AB  - BACKGROUND: Congenital heart defects, including conotruncal anomalies, are often
      associated with arrhythmias. Bis-diamine induces conotruncal anomalies in embryos
      when administered to pregnant female rats. To investigate the mechanism of
      arrhythmia in conotruncal anomalies, we histologically examined the development
      of the cardiac conduction system in this animal model. METHODS: A single dose of
      200 mg of bis-diamine was administered to pregnant Wistar rats on ED 10.5 of
      pregnancy. The embryos were removed on each day from ED 11.5 to 15.5.
      Immunoexpression of HNK-1, connexin40, and connexin43 were examined in serial
      sections. The distribution pattern of TUNEL-positive cells around the conduction
      system was also examined. RESULTS: HNK-1 immunoreactivity was evident in
      interventricular septum, in both the control and the bis-diamine-treated embryos
      from ED 12.5. Although a chain of connexin40-immunoreactive cells from
      interventricular septum to trabeculae, corresponding to the His bundle and its
      branches, was demonstrated at ED 13.5 in the control embryos, this chain was
      first detected at ED 14.5 in the bis-diamine-treated embryos. Immunoexpression of
      connexin43 in the working myocardium was also less in the bis-diamine-treated
      embryos than in the control at ED 13.5. The number of TUNEL-positive cells in the
      interventricular septum was highest at ED 12.5 in the control and at ED 13.5 in
      the bis-diamine-treated embryos. Furthermore, these TUNEL-positive cells were HNK
      1 negative, vimentin-positive, and alpha smooth muscle actin-positive.
      CONCLUSIONS: Bis-diamine disturbed the normal development of gap junctions and
      apoptosis of myofibroblasts around the HNK-1-positive conduction tissue through
      overall poor myocardial proliferation and growth.

PMID- 15965975
TI  - Transcriptional analysis of multiple brain regions in Parkinson's disease
      supports the involvement of specific protein processing, energy metabolism, and
      signaling pathways, and suggests novel disease mechanisms.
AB  - In both genetic and idiopathic forms of Parkinson's disease (PD), considerable
      evidence supports the involvement of alpha-synuclein, electron transport chain
      complex I, protein aggregation, and the ubiquitin-proteasome system. To
      investigate alterations in the transcription of genes that comprise these
      pathways, we performed gene expression profiling and functional gene group
      analysis of three brain regions (the substantia nigra, putamen, and area 9) in
      postmortem tissue from matched groups of PD or control subjects (n = 15/group).
      Verification of selected changes was performed using RT-PCR, and visualization of
      selected changes in expression was accomplished using in situ hybridization
      (ISH). Our results provide strong support for the impairment of multiple electron
      transport chain complexes and the ubiquitin-proteasomal system in PD, along with
      a robust induction of heat shock proteins and some anti-apoptotic gene groups.
      Several novel gene and gene group findings were also obtained that offer new
      insight into the pathogenesis and potential treatment of PD.

PMID- 15965976
TI  - Spermatogenesis in testis primary cell cultures of the tilapia (Oreochromis
      niloticus).
AB  - Spermatogenesis in vertebrates is controlled by endocrine and paracrine factors
      and involves the communication between somatic and germ line cells. To elucidate
      some of the relevant factors in the complicated molecular control processes, we
      established an in vitro test system using primary cultures of tilapia
      (Oreochromis niloticus) testis cells. The cultures were enriched for germ line
      cells and Sertoli cells and largely depleted of spermatozoa. By staining the
      cells with propidium iodide and carboxyfluorescein succinimidyl ester (CFSE),
      different cell populations could be identified cytologically and, in addition,
      quantified by flow cytometry. Cells that had gone through one or more divisions
      could be identified unequivocally based on their CFSE staining intensity. In
      parallel cultures maintained for up to 16 days in the presence of 11
      ketotestosterone (KT), insulin-like growth factor I (IGF), and/or human chorionic
      gonadotropin (hCG) the initiation of meiotic and mitotic divisions was monitored.
      Although KT was important for the initiation of meiosis, spermatogonial mitotic
      divisions between 10 days and 16 days of culture were promoted by IGF and/or hCG
      in the presence of KT. These results illustrate the potential of the established
      in vitro test system for the analysis of the molecular control mechanisms of
      spermatogenesis.

PMID- 15965977
TI  - Characterization of a human rhomboid homolog, p100hRho/RHBDF1, which interacts
      with TGF-alpha family ligands.
AB  - The activity of the TGF-alpha-like ligand Spitz in Drosophila depends on
      Rhomboid, a seven-transmembrane spanning protein that resides in the Golgi and
      acts as a serine protease to cleave Spitz, thereby releasing the soluble ligand.
      Several rhomboids in Drosophila have been implicated in the processing of TGF
      alpha-like ligands, and consequent EGF receptor activation. The larger number of
      TGF-alpha-like ligands in vertebrates raises the possibility that they too might
      be subject to regulation by rhomboid-like proteins. We present the cDNA cloning
      and polypeptide sequence of an atypically long human rhomboid, which, based on
      the absence of critical residues for serine protease activity, is not predicted
      to act as a serine protease. We examined its tissue distribution, in comparison
      with TGF-alpha and the TGF-alpha-related protein HB-EGF, and the EGF/TGF-alpha
      receptor, in mouse embryo. This rhomboid, named p100(hRho) or RHBDF1, is a seven
      transmembrane protein with a long N-terminal cytoplasmic extension that comprises
      half of the polypeptide sequence, and is found in the endoplasmic reticulum and
      Golgi, but not on the cell surface. It is expressed as two forms with different
      lengths, forms dimers and interacts with TGF-alpha ligands through a luminal
      interaction with the EGF core ectodomain. Finally, we evaluated the function of
      p100(hRho)/RHBDF1 in Drosophila, demonstrating that the short, but not the full
      length form has functional activity. The characterization of this protein extends
      our understanding of the rhomboid family of regulatory proteins.

PMID- 15965978
TI  - Muscle specification in the Xenopus laevis gastrula-stage embryo.
AB  - Recent fate maps of the Xenopus laevis gastrula show that mesodermal tissue
      surrounding the blastopore gives rise to muscle (Keller [1991] Methods Cell Biol
      36:61-113; Lane and Smith [1999] Development 126:423-434). In a significant
      deviation from earlier data, the new maps demonstrate that cells in the ventral
      half of the gastrula are precursors to a significant portion of trunk somites.
      However, these posterior somites are not formed until tadpole stages (stages 38
      44). We therefore set out to determine the timing of muscle specification within
      the ventral half of the gastrula. Our approach was to generate a series of tissue
      explants from gastrula-stage embryos and then culture them to either stage 28
      (tailbud) or stage 44 (tadpole). At each endpoint, the presence of muscle in
      explants was assessed with a muscle-specific antibody. Interestingly, we found
      that muscle tissue is detected in ventral explants. However, these explants must
      be cultured to the tadpole stage. This is perhaps not unexpected, as this is the
      point at which this tissue normally gives rise to muscle. We further show that
      muscle specification of the involuting marginal zone does not change over the
      course of gastrulation. Together, these results suggest that dorsalizing signals
      emanating from the midline during gastrulation are not necessary for muscle
      specification of the ventral half of the involuting marginal zone.

PMID- 15965979
TI  - BMPR2 mutations have short lifetime expectancy in primary pulmonary hypertension.
AB  - In a nationwide study, we identified a total of 59 patients diagnosed with
      primary pulmonary hypertension (PPH) in Finland between the years 1987 and 1999.
      These data support a minimum estimate for a PPH population prevalence of 5.8
      cases/million with an incidence of 0.2-1.3 cases/million/year. The male-to-female
      ratio among the patients was 1:4, while 7% (4/59) of the PPH probands had a known
      family history of the disorder. Familial or sporadic PPH showed no geographic
      clustering to any region of Finland. Sequencing of the coding regions and exon
      intron boundaries of the bone morphogenetic protein receptor type 2 (BMPR2)
      identified heterozygous BMPR2 mutations in 12% (3/26) of the sporadic and 33%
      (1/3) of the familial patients. All four mutations were different, and two of
      those have been previously reported in other populations. Pathogenic defects in
      BMPR2 include a novel missense mutation (c.2696G>C encoding R899P), located
      within the receptor intracellular cytoplasmic domain whose function has been
      poorly characterized. Our analysis demonstrates that this mutant, while
      localizing to the cell surface, does not impact on SMAD-mediated (mothers against
      decapentaplegic homolog) intracellular signaling, but leads to constitutive
      activation of the p38(MAPK) pathway. The absence of a founder mutation in a
      genetically homogeneous population, such as the Finns, suggests that all
      identified BMPR2 mutations have to be rather young while the ancestral (if any)
      mutations have been lost either due to repetitive genetic bottlenecks or due to
      significant negative selection. Hum Mutat 26(2), 1-6, 2005. (c) 2005 Wiley-Liss,
      Inc.

PMID- 15965980
TI  - Dynamic EGFR-Ras signalling in Drosophila leg development.
AB  - In Drosophila, as in many other animals, EGFR-Ras signalling has multiple
      developmental roles from oogenesis to differentiation. In leg development, in
      particular, it has been described to be responsible for the establishment of
      distal leg fates in a graded manner. Here, we investigate the patterns of
      expression of activators of EGFR-Ras signalling, as well as some of the
      effectors, in order to better understand the patterning of the distal leg, and to
      investigate further roles of this signalling pathway. These patterns, together
      with genetic data obtained by different mutant conditions for EGFR-Ras members
      and transgene expression, suggest two rounds of signalling in leg development.
      Early, the EGFR ligand Vein is the main player in distal leg patterning, possibly
      supported later by another ligand activated by Rhomboid. Later, in a second wave
      of signalling when all the proximal-distal leg fates have been specified, domains
      of EGFR/Ras activation appear inside each leg segment to regulate Notch-mediated
      joint development, and also some organs such as tendons and sensory organs. This
      second wave relies on a ligand activated by Rhomboid.

PMID- 15965981
TI  - Ex ovo electroporation for gene transfer into older chicken embryos.
AB  - In ovo electroporation is an excellent method to ectopically induce or inhibit
      gene expression in chicken embryos and to study the in vivo function of genes
      during embryonic development. However, the application of electroporation in ovo
      to date is limited to an early stage of incubation (< stage 20). In older embryos
      (> stage 22), the vitelline and allantoic vessels have developed extensively and
      the in ovo manipulation of the embryo becomes exceedingly difficult. Therefore,
      in this study, we validate an ex ovo electroporation system, by which the time
      for performing electroporation can be extended up to at least day 7 of
      incubation. The application of this method will help to study gene function and
      regulation at later stages of development in the living chicken embryo.

PMID- 15965982
TI  - An examination of non-formalin-based fixation methods for Xenopus embryos.
AB  - Despite the growing availability of non-formalin-based fixatives, the vast
      majority of researchers in developmental biology continue to fix embryos and
      tissue in 4% paraformaldehyde. This fixation method has proven useful for both
      immunohistochemistry and in situ hybridization, yet working with paraformaldehyde
      has distinct disadvantages in its toxicity and the short shelf life of prepared
      solutions. In a search for viable alternative fixatives, we have evaluated two
      non-formalin-based commercial products, FineFIX (Milestone Microwave Laboratory
      System) and NOTOXhisto (Scientific Device Laboratory). These products were tested
      side-by-side with a commonly used 4% paraformaldehyde solution (MEMPFA) on
      Xenopus laevis embryos and assayed using whole mount immunohistochemistry and
      whole mount in situ hybridization. The results indicate that NOTOXhisto can be
      used as a substitute for MEMPFA in both tested Xenopus protocols with no loss of
      sensitivity or tissue morphology.

PMID- 15965983
TI  - Expression of heat-shock protein 70 during limb development and regeneration in
      the axolotl.
AB  - Urodele amphibians (e.g., axolotls) have the unique ability, among vertebrates,
      to regenerate perfectly many parts of their body after amputation. The limb has
      been the most widely studied regenerating structure in these organisms and
      provides an ideal model in which to understand how vertebrates can regenerate
      complex tissues. The present study focuses on Hsp-70, a member of the stress
      related heat-shock protein family. This protein is normally induced after a
      stress or trauma such as heat-shock, ultraviolet irradiation, or wounding. Thus,
      studying its expression during axolotl limb regeneration, a response to an
      important traumatic event (amputation), is of great interest to further
      understand how the regenerative process is mediated. Using molecular biology and
      biochemical techniques, we have characterized both the spatiotemporal and
      quantitative expression patterns of Hsp-70 in axolotl development and
      regeneration. Our results show that Hsp-70 is expressed and regulated during
      axolotl development as in other vertebrates. Our data also demonstrate an up
      regulation of the RNA transcript for Hsp-70 during limb regeneration as early as
      24 hr after amputation that is maintained up to early differentiation. We also
      demonstrate a similar pattern of expression for the protein during regeneration.
      Finally, we show that axolotl Hsp-70 is induced threefold after heat-shock as
      observed in other vertebrates.

PMID- 15965984
TI  - Organization and developmental expression of an amphibian vascular smooth muscle
      alpha-actin gene.
AB  - A gene encoding a putative homologue of the avian and mammalian vascular smooth
      muscle alpha-actin was isolated from an amphibian, Rana catesbeiana, and
      characterized in terms of its sequence, organization, and expression pattern. To
      assess the expression of this gene during amphibian embryonic development, a cDNA
      encoding the Xenopus homologue of this mRNA was isolated and characterized by in
      situ hybridization. The expression of this gene was not detected in the enteric
      smooth muscle cells or, unlike its avian and mammalian homologues, in the
      somites/skeletal muscle of the Xenopus embryos/tadpoles. Its initial expression
      coincides with the onset of cardiac muscle differentiation and is coincidental
      with the expression of the cardiac alpha-actin mRNAs in the heart-forming region
      of the stage 26/27 embryo. As development proceeds, transcripts from this gene
      are expressed throughout the developing heart until the formation of the heart
      chambers is completed and, thereafter, its expression becomes restricted to the
      outflow tract of the tadpole heart. The subsequent restricted expression of this
      gene to the vascular system in both of these amphibians identifies it as the
      amphibian homologue of the avian and mammalian vascular smooth muscle alpha
      actin.

PMID- 15965985
TI  - Thermodynamic and dynamic factors involved in the stability of native protein
      structure in amorphous solids in relation to levels of hydration.
AB  - The internal, dynamical fluctuations of protein molecules exhibit many of the
      features typical of polymeric and bulk small molecule glass forming systems. The
      response of a protein's internal molecular mobility to temperature changes is
      similar to that of other amorphous systems, in that different types of motions
      freeze out at different temperatures, suggesting they exhibit the alpha-beta
      modes of motion typical of polymeric glass formers. These modes of motion are
      attributed to the dynamic regimes that afford proteins the flexibility for
      function but that also develop into the large-scale collective motions that lead
      to unfolding. The protein dynamical transition, T(d), which has the same meaning
      as the T(g) value of other amorphous systems, is attributed to the temperature
      where protein activity is lost and the unfolding process is inhibited. This
      review describes how modulation of T(d) by hydration and lyoprotectants can
      determine the stability of protein molecules that have been processed as bulk,
      amorphous materials. It also examines the thermodynamic, dynamic, and molecular
      factors involved in stabilizing folded proteins, and the effects typical
      pharmaceutical processes can have on native protein structure in going from the
      solution state to the solid state.

PMID- 15965986
TI  - Large-scale propagation of four undifferentiated human embryonic stem cell lines
      in a feeder-free culture system.
AB  - We describe an improved and more robust protocol for transfer and subsequent
      propagation of human embryonic stem cells under feeder-free conditions. The
      results show that mechanical dissociation for transfer of the human embryonic
      stem cells to Matrigel resulted in highest survival rates. For passage of the
      cultures on the other hand, enzymatic dissociation was found to be most
      efficient. In addition, this method reduces the time, work, and skills needed for
      propagation of the human embryonic stem cells. With the present protocol, the
      human embryonic stem cells have been cultured under feeder-free conditions for up
      to 35 passages while maintaining a normal karyotype, stable proliferation rate,
      and high telomerase activity. Furthermore, the feeder-free human embryonic stem
      cell cultures express the transcription factor Oct-4, alkaline phosphatase, and
      cell surface markers SSEA-3, SSEA-4, Tra 1-60, Tra 1-81, and formed teratomas in
      severe combined immunodeficient mice. This method provides distinct advantages
      compared with previous protocols and make propagation of human embryonic stem
      cells less laborious and more efficient.

PMID- 15965987
TI  - Evaluation of two methods for assessing gene-environment interactions using data
      from the Danish case-control study of facial clefts.
AB  - BACKGROUND: Epidemiological investigations have begun to consider gene
      environment (GE) interactions as potential risk factors for many diseases,
      including several different birth defects. However, traditional methodological
      approaches for the analysis of case-control data tend to have low power for
      detection of interaction effects. A log-linear approach that can impose the
      assumption that the genotype and exposure of interest occur independently in the
      population has been proposed as a potentially more powerful method for assessing
      GE interactions but has not been widely applied in the published literature.
      METHODS: The present analyses were undertaken to compare the results obtained
      when stratified analyses and a log-linear approach were used to assess potential
      GE interactions. The analyses were conducted using data from a population-based,
      case-control study conducted in Denmark and considered associations between
      nonsyndromic cleft lip with or without cleft palate (CL+/-P), infant genotype for
      variants of RAR-alpha, TGF-alpha, TGF-beta3, and MSX1, and maternal exposure to
      smoking, alcohol, and multivitamins. RESULTS: Neither the stratified nor the log
      linear analyses provided evidence that that risk of CL+/-P is influenced by any
      of the GE interactions that were evaluated, despite the potential increase in
      power offered by the latter approach. Further, the analyses highlight concerns
      regarding the power to reject the assumption of independence of the genetic and
      environmental factor of interest in the controls and related concerns regarding
      the validity of results obtained using the log-linear approach when the
      underlying assumption is violated. CONCLUSIONS: The potential increase in power
      offered by the log-linear approach is offset by concerns regarding the validity
      of this approach when the independence assumption is violated.

PMID- 15965988
TI  - High-end specificity of the children's depression inventory in a sample of
      anxiety-disordered youth.
AB  - Using a receiver operating characteristic (ROC) analysis, the present study
      investigated the ability of the Children's Depression Inventory (CDI) to
      correctly detect depression in a sample of treatment-seeking anxious youth
      (N=44). The ADIS-C/P was used to determine diagnostic status of participants.
      Anxious children who met diagnostic criteria for a depressive disorder scored
      higher on the CDI than anxious children who did not meet criteria for a
      depressive disorder, supporting the CDI as a continuous measure of depressive
      symptomatology. In contrast, with regard to detecting a depressive disorder, CDI
      cut scores did not achieve favorable values across diagnostic utility indices
      (including the cut score of 13 that has been recommended). These findings support
      the CDI as a continuous measure of depressive symptoms, but do not support the
      CDI as a sole assessment for a diagnosis of depression within a sample of anxiety
      disordered youth.

PMID- 15965989
TI  - Effects of caffeine on linear and nonlinear measures of heart rate variability
      before and after exercise.
AB  - Caffeine intake is associated with an increase in heart rate (HR) variability.
      This study sought to examine the effects of caffeine on HR variability measures
      before and during progressive exercise in 11 healthy volunteers in a double-blind
      randomized and counterbalanced placebo-controlled paradigm. As expected, there
      were significant increases in HR and decreases in HR variability after exercise
      during both placebo and caffeine conditions; however, pre-exercise caffeine
      condition was associated with a significant increase of HR variability,
      especially in the high-frequency range (0.15-0.5 Hz), and also approximate
      entropy (APEN), which is usually attributed to cardiac vagal function. But during
      progressive exercise, caffeine intake resulted in a greater decrease of HF power
      as well as HR APEN. Caffeine also was associated with significantly higher LF
      power during exercise compared to the placebo condition. These results suggest
      that caffeine may have different effects on HR variability at rest, compared to
      exercise. These findings may have implications for patients with cardiac illness
      and anxiety, depression, and psychotic disorders who use beverages containing
      excessive caffeine.

PMID- 15965990
TI  - Pc 4 photodynamic therapy of U87-derived human glioma in the nude rat.
AB  - BACKGROUND AND OBJECTIVES: As a potential therapy for malignant glioma, we tested
      the phthalocyanine photosensitizer Pc 4 for: (1) rapid clearance from the
      vasculature, (2) specificity for glioma, and (3) tumoricidal photosensitizing
      capability. STUDY DESIGN/MATERIALS AND METHODS: Parenchymal injection of U87
      cells into athymic rat brains (N = 100) was followed after 12 days by tail vein
      injection of 0.5 mg/kg Pc 4. After 1 day, the tumor was illuminated with either 5
      (N = 11) or 30 (N = 16) J/cm(2) red light at 672 nm. Sacrifice was 1 day later.
      The brains from these 27 animals underwent H&E (necrosis) and TUNEL assay
      (apoptosis) histology. Pc 4 concentration of explanted brains and tumors (N =
      16), and all blood samples (N = 52) were determined by HPLC-MS 1 day post Pc 4
      administration. RESULTS: Tumor-specific apoptosis was almost uniformly seen;
      however, necrosis was found mostly in the high-light-dose group. Pc 4
      concentration in bulk tumor averaged 3.8 times greater than in normal brain.
      CONCLUSIONS: These results warrant expanding this pre-clinical study to seek
      effective baseline Pc 4 drug- and light-doses and infusion-to-photoirradiation
      timing that would be necessary for a Pc 4-mediated PDT clinical trial for glioma
      patients.

PMID- 15965991
TI  - Photodynamic therapy of head and neck basal cell carcinoma according to different
      clinicopathologic features.
AB  - BACKGROUND AND OBJECTIVES: We aimed to treat different pathologic types of basal
      cell carcinomas (BCCs) using photodynamic therapy (PDT). STUDY DESIGN/MATERIALS
      AND METHODS: Thirty lesions in six patients underwent PDT. The photosensitizer
      used was Photoheme, a hematoporphyrin derivative IX. It was injected
      intravenously at the dose of 2-3.25 mg/kg. After 24 hours, the lesions were
      illuminated by laser light (lambda = 632 nm, light exposure dose = 100-200
      J/cm2). Lesions were evaluated pre and post-operatively and at follow-up sessions
      (of up to 6 months). RESULTS: After a single session of PDT, the average response
      rate in different histopathologic kinds of basal cell carcinoma (e.g.,
      ulcerative, superficial, nodular, and pigmented forms) were 100%, 62%, 90%, and
      14%, respectively. In patients who responded completely, the cosmetic results
      were excellent and there were no recurrence at 6th month of follow-up.
      CONCLUSION: Although PDT seems to be an effective treatment modality for
      superficial, ulcerative, and nodular BCCs, it is not recommended for pigmented
      lesions.

PMID- 15965993
TI  - Influence of the serotonin transporter promoter gene polymorphism on
      susceptibility to posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent anxiety disorder marked by
      behavioral, physiologic, and hormonal alterations. The etiology of PTSD is
      unknown, although exposure to a traumatic event constitutes a necessary, but not
      sufficient, factor. Serotonergic dysfunction has been implicated in PTSD. The
      present study examined the possible association between the serotonin-transporter
      linked polymorphic region (SERTPR) and PTSD. The genotype and allele frequencies
      of the SERTPR were analyzed in 100 PTSD patients and 197 unrelated healthy
      controls using a case-control design. The frequency of the s/s genotype was
      significantly higher in PTSD patients than in normal controls. These findings
      suggest that the SERTPR s/s genotype is one of the genetic factors for the
      susceptibility to PTSD. Further investigations are required into the influence of
      gene polymorphisms on the biological mechanisms of PTSD, its clinical expression,
      and its response to treatment.

PMID- 15965994
TI  - Influence of age of onset on clinical features in obsessive-compulsive disorder.
AB  - We compared early-onset and late-onset obsessive-compulsive disorder (OCD)
      patients in terms of demographic and clinical features. One hundred sixteen
      outpatients whose primary diagnosis was OCD according to DSM-IV diagnostic
      criteria were recruited. Early-onset (n=50) and late-onset (n=66) OCD groups were
      compared with respect to demographic variables and scores obtained on various
      scales. A male gender predominance was found in early-onset OCD group.
      Symmetry/exactness obsessions, religious obsessions, hoarding/saving obsessions,
      and hoarding/collecting compulsions also were significantly more frequent in the
      early-onset group than in the late-onset group. The results may suggest a
      phenotypic difference between the two groups. Further studies are needed to
      investigate the differences between early-onset and late-onset OCD groups to
      examine the hypothesis that early-onset OCD is a distinct subtype of the
      disorder.

PMID- 15965995
TI  - The expression of anger and its relationship to symptoms and cognitions in
      obsessive-compulsive disorder.
AB  - We compared the association between obsessive-compulsive disorder (OCD) and the
      expression of anger in a sample of 71 patients and 71 college students. Some
      authors [Rubenstein et al., J Anxiety Disord 1995;9:1-9] have proposed that anger
      and hostility underlie the symptoms of OCD; however, there has been little
      empirical study of this relationship. One recent study [Whiteside and Abramowitz,
      Cog Therapy Res 2004;28:259-268] with college undergraduates found that the
      association between OCD symptoms and anger was attributable to depressive
      symptoms. In the present study, we compared the expression of anger in a sample
      of patients diagnosed with OCD and nonclinical volunteers. Consistent with the
      previous study, we found increased levels of anger in patients with OCD as
      compared to control participants; however, these differences could be attributed
      to between-group differences in general distress. These results were discussed
      within the framework of the cognitive theory of OCD.

PMID- 15965996
TI  - Beliefs about psychotropic medication and psychotherapy among primary care
      patients with anxiety disorders.
AB  - Primary health care clinics are increasingly providing psychiatric/psychological
      treatment of anxiety disorders, particularly for patients who do not have
      adequate access to specialty mental health services. Adequate treatment requires
      knowledge of and attention to patients' beliefs about available treatment
      options. The current investigation examined beliefs about psychotropic
      medications and psychotherapy among a sample of primary care patients with
      anxiety disorders. The influence of key demographic variables on strength of
      these beliefs was also explored. The presence of specific anxiety disorders was
      not found to impact strength of beliefs about either type of treatment. In
      contrast, there was a trend for the presence of depression to relate to more
      favorable attitudes toward psychotropic medication. Consistent with previous
      studies, ethnic minority patients reported less favorable attitudes toward both
      psychotropic medications and psychotherapy. These findings underscore the
      importance of assessing patient beliefs prior to the initiation of either
      psychotropic medications or psychotherapy across diagnostic and demographic
      groups. Practitioners should be particularly alert to the possibility that
      patients with anxiety disorders and members of ethnic minority groups may have
      less favorable attitudes toward treatment options. Treatment adherence may
      therefore be increased by addressing these beliefs directly.

PMID- 15965997
TI  - Evaluation of the psychometric properties of the Beck Depression Inventory in a
      non-elderly adult sample of patients with generalized anxiety disorder.
AB  - Although the Beck Depression Inventory (BDI) is commonly administered across a
      wide range of psychological disorders, its psychometric properties have not yet
      been examined in a non-elderly (aged 59 years or younger) adult sample of
      patients with generalized anxiety disorder (GAD). Completed BDIs were obtained
      from 48 patients with GAD (mean age=31.85 years) and 41 nonanxious control
      participants (mean age=30.49 years). The BDI exhibited good internal consistency
      in the clinical sample. Patients obtained more extreme scores on the BDI than did
      control participants, and patients with a comorbid mood disorder obtained more
      extreme scores on the BDI than did patients without a comorbid mood disorder.
      Patients' BDI scores correlated significantly more strongly with a clinician
      administered measure of depression than with self-report measures of generalized
      anxiety, worry, social anxiety, or anxiety sensitivity, but not more strongly
      than with a clinician-administered measure of anxiety. BDI scores correlated
      positively with self-reported disability and negatively with life satisfaction.
      Overall, the BDI demonstrated good psychometric properties in this non-elderly
      adult sample of patients with GAD.

PMID- 15965998
TI  - Interpersonal psychotherapy for depression with panic spectrum symptoms: a pilot
      study.
AB  - Patients whose depression is complicated by a lifetime history of panic symptoms
      display a poorer treatment response to both psychotherapeutic and pharmacologic
      interventions. A newly adapted psychosocial treatment for depression with
      lifetime panic spectrum symptoms was evaluated in an open pilot study.

PMID- 15965999
TI  - Spatial interference during bimanual coordination: differential brain networks
      associated with control of movement amplitude and direction.
AB  - Bimanual interference emerges when spatial features, such as movement direction
      or amplitude, differ between limbs, as indicated by a mutual bias of limb
      trajectories. Although first insights into the neural basis of directional
      interference have been revealed recently, little is known about the neural
      network associated with amplitude interference. We investigated whether amplitude
      versus directional interference activates differential networks. Functional
      magnetic resonance imaging (fMRI) was applied while subjects performed cyclical,
      bimanual joystick movements with either the same vs. different amplitudes,
      directions, or both. The kinematic analysis confirmed that subjects experienced
      amplitude interference when they moved with different as compared to the same
      amplitude, and directional interference when they moved along different as
      compared to the same direction. On the brain level, amplitude and directional
      interference both resulted in activation of a bilateral superior parietal
      premotor network, which is known to contribute to sensorimotor transformations
      during goal-directed movements. Interestingly, amplitude but not directional
      interference exclusively activated a bilateral network containing the
      dorsolateral prefrontal cortex, anterior cingulate, and supramarginal gyrus,
      which was shown previously to contribute to executive functions. Even though the
      encoding of amplitude and directional information converged and activated the
      same neural substrate, our data thus show that additional and partly independent
      mechanisms are involved in bimanual amplitude as compared to that in directional
      control.

PMID- 15966000
TI  - Segmentation of skull and scalp in 3-D human MRI using mathematical morphology.
AB  - We present a new technique for segmentation of skull and scalp in T(1)-weighted
      magnetic resonance images (MRIs) of the human head. Our method uses mathematical
      morphological operations to generate realistic models of the skull, scalp, and
      brain that are suitable for electroencephalography (EEG) and
      magnetoencephalography (MEG) source modeling. We first segment the brain using
      our Brain Surface Extractor algorithm; using this, we can ensure that the brain
      does not intersect our skull segmentation. We next generate a scalp mask using a
      combination of thresholding and mathematical morphology. We use the scalp mask in
      our skull segmentation procedure, as it allows us to automatically exclude
      background voxels with intensities similar to those of the skull. We find the
      inner and outer skull boundaries using thresholding and morphological operations.
      Finally, we mask the results with the scalp and brain volumes to ensure closed
      and nonintersecting skull boundaries. Visual evaluation indicated accurate
      segmentations of the cranium at a gross anatomical level (other than small holes
      in the zygomatic bone in eight subjects) in all 44 MRI volumes processed when run
      using default settings. In a quantitative comparison with coregistered CT images
      as a gold standard, MRI skull segmentation accuracy, as measured using the Dice
      coefficient, was found to be similar to that which would be obtained using CT
      imagery with a registration error of 2-3 mm.

PMID- 15966001
TI  - Lexical and sentential processing in British Sign Language.
AB  - Studies of spoken and written language suggest that the perception of sentences
      engages the left anterior and posterior temporal cortex and the left inferior
      frontal gyrus to a greater extent than non-sententially structured material, such
      as word lists. This study sought to determine whether the same is true when the
      language is gestural and perceived visually. Regional neural activity was
      measured using functional MRI while Deaf and hearing native signers of British
      Sign Language (BSL) detected semantic anomalies in well-formed BSL sentences and
      when they detected nonsense signs in lists of unconnected BSL signs. Processing
      BSL sentences, when contrasted with signed lists, was reliably associated with
      greater activation in the posterior portions of the left middle and superior
      temporal gyri and in the left inferior frontal cortex, but not in the anterior
      temporal cortex, which was activated to a similar extent whether lists or
      sentences were processed. Further support for the specificity of these areas for
      processing the linguistic-rather than visuospatial-features of signed sentences
      came from a contrast of hearing native signers and hearing sign-naive
      participants. Hearing signers recruited the left posterior temporal and inferior
      frontal regions during BSL sentence processing to a greater extent than hearing
      non-signers. These data suggest that these left perisylvian regions are
      differentially associated with sentence processing, whatever the modality of the
      linguistic input.

PMID- 15966002
TI  - Location and spatial profile of category-specific regions in human extrastriate
      cortex.
AB  - Subjects were scanned in a single functional MRI (fMRI) experiment that enabled
      us to localize cortical regions in each subject in the occipital and temporal
      lobes that responded significantly in a variety of contrasts: faces>objects, body
      parts>objects, scenes>objects, objects>scrambled objects, and moving>stationary
      stimuli. The resulting activation maps were co-registered across subjects using
      spherical surface coordinates [Fischl et al., Hum Brain Mapp 1999;8:272-284] to
      produce a "percentage overlap map" indicating the percentage of subjects who
      showed a significant response for each contrast at each point on the surface.
      Prominent among the overlapping activations in these contrasts were the fusiform
      face area (FFA), extrastriate body area (EBA), parahippocampal place area (PPA),
      lateral occipital complex (LOC), and MT+/V5; only a few other areas responded
      consistently across subjects in these contrasts. Another analysis showed that the
      spatial profile of the selective response drops off quite sharply outside the
      standard borders of the FFA and PPA (less so for the EBA and MT+/V5), indicating
      that these regions are not simply peaks of very broad selectivities spanning
      centimeters of cortex, but fairly discrete regions of cortex with distinctive
      functional profiles. The data also yielded a surprise that challenges our
      understanding of the function of area MT+: a higher response to body parts than
      to objects. The anatomical consistency of each of our functionally defined
      regions across subjects and the spatial sharpness of their activation profiles
      within subjects highlight the fact that these regions constitute replicable and
      distinctive landmarks in the functional organization of the human brain.

PMID- 15966004
TI  - Stages 1-2 non-rapid eye movement sleep behavior disorder associated with
      dementia: a new parasomnia?
AB  - A 55-year-old woman with a progressive dementia and frontal syndrome was
      hospitalized because she was agitated every night after falling asleep (spoke,
      laughed, cried, tapped, kicked, walked, and fell down). She slept 5.5 hours
      during video polysomnography, but the theta rhythm electroencephalograph
      recording typical of sleep stages 1 to 2 and the spindles and K-complexes typical
      of sleep stage 2 contrasted with continuous muscular twitching, prominent rapid
      eye movements, vocalizations, and continuous, complex, purposeful movements
      typical of rapid eye movement (REM) sleep behavior disorder. This newly described
      stages 1--2 non-REM sleep behavior disorder suggests that central motor pattern
      generators were disinhibited during non-REM sleep.

PMID- 15966003
TI  - Absence of previously reported variants in the SCNA (G88C and G209A), NR4A2
      (T291D and T245G) and the DJ-1 (T497C) genes in familial Parkinson's disease from
      the GenePD study.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder in which relatives of
      the probands are affected approximately 4 times as frequently as relatives of
      control subjects. Several genes have been implicated as genetic risk factors for
      PD. We investigated the presence of six reported genetic variations in the SCNA,
      NR4A2, and DJ-1 genes in 292 cases of familial Parkinson's disease from the
      GenePD study. None of the variants were found in the GenePD families. Our results
      suggest that other variants or genes account for the familial risk of PD within
      the GenePD study.

PMID- 15966005
TI  - Neuronal intranuclear inclusion disease: report on a case originally diagnosed as
      dopa-responsive dystonia with Lewy bodies.
AB  - Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative
      disorder with a heterogeneous clinical picture characterized by the presence of
      eosinophilic intranuclear inclusions in neuronal and glial cells. We describe a
      case, reported 12 years ago as dopa-responsive dystonia (DRD) with Lewy body
      pathology. Pathological re-examination has led to a revised diagnosis of neuronal
      intranuclear inclusion disease. This rare condition, which may be diagnosed in
      life with a full thickness rectal biopsy, needs to be considered in the
      differential diagnosis of any case presenting as progressive juvenile
      parkinsonism (JP) or dystonia.

PMID- 15966006
TI  - Genomic convergence to identify candidate genes for Parkinson disease: SAGE
      analysis of the substantia nigra.
AB  - Genomic convergence is a multistep approach that combines gene expression with
      genomic linkage to identify and prioritize susceptibility genes for complex
      disease. As a first step, we previously performed linkage analysis on 174
      multiplex Parkinson's disease (PD) families, identifying five peaks for PD risk
      and two for genes affecting age at onset (AAO) in PD [Hauser et al., Hum Mol
      Genet 2003;12:671-677]. We report here the next step: serial analysis of gene
      expression [SAGE; Scott et al., JAMA 2001;286:2239-2242] to analyze substantia
      nigra tissue from three PD patients and two age-matched controls. We find 933
      differentially expressed genes (P<0.05) between PD and controls, but of these,
      only 50 genes represented by unique SAGE tags map within our previously described
      PD linkage regions. Furthermore, genes encoded by mitochondrial DNA are expressed
      1.5-fold higher in PD patients versus controls, without an increase in the
      corresponding nuclear-encoded mitochondrial components, suggesting an increase in
      mtDNA genomes in PD or a disjunction with nuclear expression. The next step in
      the genomic convergence process will be to screen these 50 high-quality candidate
      genes for association with PD risk susceptibility and genetic effects on AAO.

PMID- 15966007
TI  - A quantitative investigation into the losses of proteins at different stages of a
      two-dimensional gel electrophoresis procedure.
AB  - We report the results of a systematic investigation to quantify the losses of
      protein during a well-established two-dimensional polyacrylamide gel
      electrophoresis (2-DE) procedure. Radioactively labelled proteins ([(14)C]bovine
      serum albumin and a homogenate prepared from the liver of a rat that had been
      injected with [(35)S]methionine) were used, and recovery was quantified by
      digesting pieces of gel in H(2)O(2) and subjecting the digests to liquid
      scintillation counting. When samples were loaded onto the first dimension
      immobilised pH gradient strips by in-gel rehydration, recovery of protein from
      the strips was 44-80% of the amount of protein loaded, depending on the amount of
      protein in the sample. Most of the unrecovered protein appeared to have adhered
      to the reswelling tray. Losses during isoelectric focusing (IEF) were much
      smaller (7-14%), although approximately 2% of the protein appeared to migrate
      from sample strips to adjacent blank strips in the focussing apparatus. A further
      17-24% of the proteins were lost into the buffers during equilibration prior to
      running in the second dimension. Losses during the second dimension run and
      subsequent staining with SYPRO Ruby amounted to less than 10%. The overall loss
      during 2-DE was reduced by approximately 25% when proteins were loaded onto the
      IEF strips using sample cups instead of by in-gel rehydration. These extensive
      and variable losses during the 2-DE procedure mean that spot intensities on 2-DE
      gels cannot be used to derive reliable, quantitative information on the amounts
      of proteins present in the original sample.

PMID- 15966008
TI  - Oxidation of carboxyamidomethyl cysteine may add complexity to protein
      identification.
AB  - Protein identification by interrogation of databases requires a comprehensive
      compilation of modified amino acids forms. Here, we describe the chemical
      oxidation of carboxyamidomethyl cysteine to the sulfoxide and sulfone forms,
      species that may add more complexity to peptide analyses. They can be easily
      distinguished by tandem mass spectrometry (MS/MS) due to their characteristic
      pattern of side chain neutral eliminations either from the parent ion or ion
      series that generate dehydroalanine as detected by MS(3). This finding was
      supported by the MS(n) spectra recorded for a peptide isolated from a mixture of
      tryptic peptides and for a derivatized/oxidized synthetic peptide with a
      different sequence. These modifications and their diagnostic neutral losses
      should be included in the list of chemical modifications and in algorithms
      designed for the automatic sequencing of peptides and database searching.

PMID- 15966009
TI  - Decoding two-dimensional polyacrylamide gel electrophoresis complex maps by
      autocovariance function: a simplified approach useful for proteomics.
AB  - This paper describes a mathematical approach applied for decoding the complex
      signal of two-dimensional polyacrylamide gel electrophoresis maps of protein
      mixtures. The method is helpful in extracting analytical information since
      separation of all the proteins present in the sample is still far from being
      achieved and co-migrating proteins are generally present in the same spot. The
      simplified method described is based on the study of the 2-D autocovariance
      function (2D-ACVF) computed on an experimental digitized map. The first part of
      the 2D-ACVF allows for the estimation of the number of proteins present in the
      sample (2D-ACVF computed at the origin) and of the separation performance (mean
      spot size). Moreover, the 2D-ACVF plot is a powerful tool in identifying order in
      the spot position, and singling it out from the complex separation pattern. This
      method was validated on synthetic maps obtained by computer simulation to
      describe 2-D PAGE real maps and reference maps retrieved from the SWISS-2DPAGE
      database. The results obtained are discussed by focusing on specific information
      relevant in proteomics: sample complexity, separation performance, and
      identification of spot trains related to post-translational modifications.

PMID- 15966010
TI  - A novel technique to specifically analyze the secretome of cells and tissues.
AB  - The secretome of cells and tissues may reflect a broad variety of pathological
      conditions and thus represents a rich source of biomarkers. The identity of
      secreted proteins, usually isolated from cell supernatants or body fluids, is
      hardly accessible by direct proteome analysis, because these proteins are often
      masked by high amounts of proteins actually not secreted by the investigated
      cells. Here, we present a novel method for the specific detection of proteins
      secreted by human tissue specimen as well as cultured cells and chose liver as a
      model. The method is based on the metabolic labelling of proteins synthesized
      during a limited incubation period. Then, the cell supernatant is filtered,
      precipitated, and subjected to two-dimensional gel electrophoresis. Whereas
      fluorography detected a large number of proteins derived from residual plasma and
      dead cells, the autoradiographs selectively displayed genuinely secreted
      proteins. We demonstrate the feasibility of this approach by means of the
      secretomes of the hepatocellular carcinoma-derived cell line HepG2 and human
      liver slices. The selective identification of cell- and tissue-specific protein
      secretion profiles may help to identify novel sets of biomarkers for wide
      clinical applications.

PMID- 15966011
TI  - Separation techniques hyphenated to electrospray-tandem mass spectrometry in
      proteomics: capillary electrophoresis versus nanoliquid chromatography.
AB  - Liquid chromatography (LC) nanoelectrospray-tandem mass spectrometry (MS/MS) is a
      key technology for the study of proteomics, with the main benefit to the
      characterization of sensitive peptides from complex mixtures. Capillary
      electrophoresis coupled to mass spectrometry (MS) has been taken into
      consideration sporadically due to the highly efficient separation and ability to
      handle low sample amount, yet classified as being less sensitive with respect to
      analyte concentration. The limitation in capillary zone electrophoresis (CZE)
      injection volumes can be overcome by on-line solid-phase extraction (SPE). Such
      an on-line SPE-CZE system was explored in combination with an ion trap (IT) mass
      spectrometer. Thus, it was possible to inject more than 100 microL sample
      solution on to the CZE capillary. Concentration limits of detection as low as 100
      amol/microL were demonstrated for a peptide standard. This SPE-CZE
      microelectrospray ionization (ESI)-MS/MS setup was compared directly to
      nanoLC/nanoESI using the same sample of a tryptic digest of bovine serum albumin
      (BSA) as a reference standard. Measurements were made on one IT mass spectrometer
      with identical acquisition parameters. Both chromatography systems enabled the
      separation and detection of low levels of peptides from a mixture of moderate
      complexity, with most peptides identified using both techniques; however,
      specific differences were obvious. The nanoLC-MS is about five times more
      sensitive than the CZE-MS, yet the difference was less pronounced than expected.
      The CZE-MS technique showed reduced loss of peptides, especially for larger
      peptides (missed cleavages) and is about four times faster than the nanoLC-MS
      approach.

PMID- 15966012
TI  - Fast prototyping of hydrophobic disposable polymer support arrays for matrix
      assisted laser desorption/ionization-time of flight-mass spectrometry of proteins
      by atmospheric molding.
AB  - A fast protocol for prototyping hydrophobic disposable poly(alkyl methacrylate-co
      methyl methacrylate) copolymer sample support arrays for matrix-assisted laser
      desorption/ionization-mass spectrometry (MALDI-MS) of proteins by atmospheric
      molding is introduced. The sample support arrays were replicated by molding
      prepolymer alkyl methacrylate solutions into sandwich molds containing a
      micromachined silicon master, an aluminum spacer, and glass cover plates,
      followed by UV-initiated in situ polymerization under atmospheric pressure. The
      fabrication procedure enables a simultaneous fabrication/modification of single
      use polymer arrays by a targeted selection of functional groups of the
      copolymerized monomers during molding. The one-step modification during the
      fabrication is demonstrated for enhanced protein adsorption to the modified
      materials by introduction of hydrophobic butyl-, dodecyl-, and octadecyl groups
      to the polymer backbone without a need for additional surface coating or
      derivatization. The MALDI-MS performance of the new polymer chips was tested for
      spectral measurements of bovine pancreas insulin, horse heart myoglobin, and
      bovine serum albumin. The protein adsorption to the new hydrophobic copolymer
      chips was studied for bovine pancreas trypsinogen; the sample desalting
      parameters, such as time and volume, were optimized for myoglobin as model
      proteins. A significant signal increase was achieved after efficient desalting of
      an insect Delta11-desaturase membrane protein fragment from a complex elution
      buffer (100 mM phosphate, 10 mM tris(hydroxyethyl)aminomethane, 0.5 M NaCl, and
      10 mM ethylenediamine tetraacetic acid) on the poly(butyl methacrylate-co-methyl
      methacrylate) copolymer chip (monomer ratio 8:2 v/v) by simply washing the target
      zones. The new chips offer reduced sample manipulation and device fabrication
      times as well as simple operation.

PMID- 15966013
TI  - Age-dependent variations of cell response to oxidative stress: proteomic approach
      to protein expression and phosphorylation.
AB  - We investigated the protein profiles of variously aged rat astrocytes in response
      to oxidative stress. After H2O2-exposure of cells at 100 microM for 30 min, the
      relative intensity of ten protein spots changed on two-dimensional (2-D) gels
      compared with control gels after silver staining. Matrix-assisted laser
      desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) analysis
      after in-gel digestion revealed that six of these spots corresponded to three
      kinds of proteins, each of which was composed of a protein and its modified form
      with a different isoelectric point (pI). These three proteins were identified as
      peroxiredoxins (PRDXs) II and III, and calpactin I light chain (p11). H2O2
      exposure increased the intensity of the spot with lower pI and simultaneously
      decreased that of the spot with higher pI for both PRDXs II and III. In addition,
      the expression of annexin VII, S-adenosyl-L-homocysteine hydrolase, elongation
      factor II fragment (EF-II), and adenosine deaminase was increased by H2O2
      exposure in astrocytes from variously aged rats. Using the Pro-Q Diamond
      staining, heat shock protein 60 kDa (Hsp 60) and alpha-tubulin were observed to
      be phosphorylated upon H2O2-exposure. While phosphorylation of alpha-tubulin was
      correlated positively with age, the changes in abundance of ten protein spots as
      described above were independent of age. These results suggest that aging does
      not suppress the responses aimed at limiting injury and promoting repair brought
      about by severe oxidative stress, and might affect cell dynamics including the
      formation of microtubules.

PMID- 15966014
TI  - Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic
      purposes.
AB  - The introduction of fast, sensitive, and robust techniques for proteomic analysis
      into clinical practice represents a major step toward a new diagnostic approach
      of body fluids. In addition, proteomics emerges as a key technology for the
      discovery of disease biomarkers in various body fluids. However, even in
      relatively protein-deprived body fluids such as urine, the complexity and wide
      dynamic range of protein expression pose a considerable challenge to both
      separation and identification technologies. In the present review we discuss from
      a clinical point-of-view recent advances of the use of proteomics in clinical
      diagnosis as well as therapy evaluation. We focus on capillary electrophoresis
      coupled to mass spectrometry (CE-MS) and discuss CE-MS from an application point
      of view evaluating its merits and vices with regard to biomarker discovery. This
      review further presents examples of clinical applications of CE-MS for detection
      and identification of biomarkers in urine.

PMID- 15966015
TI  - Quantitative detection of phosphoproteins by combination of two-dimensional
      difference gel electrophoresis and phosphospecific fluorescent staining.
AB  - Here we combine a standard two-dimensional difference gel electrophoresis (DIGE)
      protocol with subsequent post-staining of gels with phosphospecific fluorescent
      Pro-Q Diamond dye. The combination of these two methods for fluorescence
      detection of proteins allows quantitative detection of phosphoproteins in 2-DE
      gels. We established this protocol within a functional proteomics experiment.
      Mammary epithelial cells (EpH4) were stimulated in culture by epidermal growth
      factor (EGF), endosomal fractions prepared after subcellular fractionation and
      phosphorylated proteins successfully detected on endosomes. For instance, Endo A
      cytokeratin, known as phosphoprotein and differentiation marker inducible by MAPK
      signaling, was identified by matrix-assisted laser desorption/ionization-time of
      flight-mass spectrometry (MALDI-TOF-MS). With this protocol, all steps of
      combined proteome and phosphoproteome profiling experiments are significantly
      simplified and accelerated, taking full advantage of both methods in terms of
      specificity, sensitivity and accuracy of quantification.

PMID- 15966016
TI  - Column chromatographic prefractionation leads to the detection of 543 different
      gene products in human fetal brain.
AB  - In a previous publication a large series of proteins were identified in fetal
      human brain by the use of two-dimensional electrophoresis (2-DE) with subsequent
      matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and MALDI
      tandem time-of-flight (TOF/TOF) analysis. Further identification of many more
      different spots by traditional 2-DE without additional step such as narrow
      immobilized ph gradient (IPG) strips or prefractionation seems unlikely and we
      therefore decided to separate extracted brain proteins by ion-exchange
      chromatography using a TSK gel DEAE-5PW column followed by 2-DE of individual
      fractions and analysis by MALDI-TOF/TOF with LIFT technology in fetal brain of
      the early second trimester. About 1880 protein spots corresponding to 543
      different gene products were identified. These proteins included housekeeping,
      signaling, cytoskeletal, metabolic, antioxidant, and neuron/synaptosomal specific
      proteins. Among these, 314 gene products (314/543, 57.8%), which have never been
      detected in traditional 2-DE of human fetal brain, were observed by this method.
      This updated map of fetal brain proteins may serve as data base and reference map
      for fetal brain proteins, and the methodology applied may be used as a valuable
      analytical tool for the basis of protein expressional studies in health and
      disease.

PMID- 15966017
TI  - Use of selective extraction and fast chromatographic separation combined with
      electrophoretic methods for mapping of membrane proteins.
AB  - A model system for selective solubilization and fast separation of proteins from
      the rat liver membrane fraction and purified rat liver plasma membranes for their
      further proteomic analysis is presented. For selective solubilization, high-pH
      solutions and a concentrated urea solution, combined with different detergents,
      are used. After extraction, proteins are separated by anion-exchange
      chromatography or a combination of anion- and cation-exchange chromatography with
      convective interaction monolithic supports. This separation method enables fast
      and effective prefractionation of membrane proteins based on their hydrophobicity
      and charge prior to one-dimensional (1-D) and 2-D electrophoresis and mass
      spectrometry. By use of this sample preparation method, the less-abundant
      proteins can be detected and identified.

PMID- 15966018
TI  - Retinal cell type expression specificity of HIV-1-derived gene transfer vectors
      upon subretinal injection in the adult rat: influence of pseudotyping and
      promoter.
AB  - BACKGROUND: Gene therapy, and particularly gene restoration, is currently a great
      hope for non-curable hereditary retinal degeneration. Clinical applications
      require a gene transfer vector capable of accurately targeting particular cell
      types in the retina. To develop such a vector, we compared the expression of a
      reporter gene after subretinal injections of lentiviral constructs of various
      pseudotypes and with the transgene expression driven by various promoters.
      METHODS: Lentiviral vectors expressing the green fluorescent protein (GFP) under
      the transcriptional control of cytomegalovirus (CMV), mouse phosphoglycerate
      kinase (PGK), human elongation factor 1-alpha (EF1alpha), or human rhodopsin
      (RHO) promoters were pseudotyped by vesicular stomatitis virus (VSV) or Mokola
      virus envelope proteins. These constructs were injected into the subretinal space
      of adult rdy rats. GFP expression was analyzed in vivo 1 and 4 weeks after
      injection by fundus examination. The precise location of transgene expression was
      then determined by immunohistochemistry and in situ hybridization. RESULTS:
      Constructs of both vesicular stomatitis virus and Mokola pseudotypes with
      ubiquitous promoters led to a strong expression of GFP in vivo. Histological
      studies confirmed the production of GFP in the retinal pigment epithelium (RPE)
      in most cases. However, only the combination of the VSV pseudotype with the RHO
      promoter led to GFP production in photoreceptors, and did so in a sporadic
      manner. CONCLUSIONS: Mokola-pseudotyped lentiviral vectors are effective for
      specific gene transfer to the RPE. Neither VSV- nor Mokola-pseudotyped lentiviral
      vectors are adequate for efficient gene transfer to photoreceptors of adult rats.

PMID- 15966019
TI  - Reduction of GAG storage in MPS II mouse model following implantation of
      encapsulated recombinant myoblasts.
AB  - BACKGROUND: Hunter syndrome, mucopolysaccharidosis type II (MPS II), is a X
      linked inherited disorder caused by the deficiency of the enzyme iduronate-2
      sulfatase (IDS), involved in the lysosomal catabolism of the glycosaminoglycans
      (GAG) dermatan and heparan sulfate. Such a deficiency leads to the intracellular
      accumulation of undegraded GAG and eventually to a progressive severe clinical
      pattern. Many attempts have been made in the last two to three decades to
      identify possible therapeutic strategies for the disorder, including gene therapy
      and somatic cell therapy. METHODS: In this study we evaluated the intraperitoneal
      implantation of allogeneic myoblasts over-expressing IDS, enclosed in alginate
      microcapsules, in the MPS II mouse model. Animals were monitored for 8 weeks post
      implantation, during which plasma and tissue IDS levels, as well as tissue and
      urinary GAG contents, were measured. RESULTS AND CONCLUSIONS: Induced enzyme
      activity occurred both in the plasma and in the different tissues analyzed. A
      significant decrease in urinary undegraded GAG between the fourth and the sixth
      week of treatment was observed. Moreover, a biochemical reduction of GAG deposits
      was measured 8 weeks after treatment in the liver and kidney, on average 30 and
      38%, respectively, while in the spleen GAG levels were almost normalized.
      Finally, the therapeutic effect was confirmed by histolochemical examination of
      the same tissues. Such effects were obtained following implantation of about 1.5
      x 10(6) recombinant cells/animal. Taken together, these results represent a clear
      evidence of the therapeutic efficacy of this strategy in the MPS II mouse model,
      and encourage further evaluation of this approach for potential treatment of
      human beings.

PMID- 15966020
TI  - Detection and quantitation of a bioactive compound in Vicia narbonensis L. seeds
      by capillary electrophoresis-mass spectrometry: a comparative study with UV
      detection.
AB  - Capillary zone electrophoresis with mass spectrometry (CE-MS) and UV detection
      (CE-UV) was applied to the quantitative determination of gamma-glutamyl-S-ethenyl
      cysteine (GEC), a bioactive and unstable compound present in Vicia narbonensis L.
      seeds. This compound is responsible for, among other negative effects,
      palatability reduction and grain toxicity. In order to carry out the quantitative
      analysis of GEC, different conditions (such as composition, concentration and pH
      of the background electrolyte, and type and time of extraction) were studied.
      Also, adequate conditions for electrospray-mass spectrometry of this bioactive
      compound were investigated. The best extraction conditions of GEC from V.
      narbonensis L. seeds flour were obtained using ethanol-water (70:30 v/v) for 45
      min. The use of a 20 m ammonium hydrogen carbonate at pH 7 provided adequate
      analytical conditions compatible with the unstable nature of GEC as well as with
      the requirements of CE-UV and CE-MS analysis. A comparative study was carried out
      between the different figures of merit of CE-UV and CE-MS for quantitative
      purposes. Both techniques provided similar limit of detection and can be applied
      with confidence within the same linear dynamic range. However, reproducibility
      and speed of analysis were better using CE-UV. The developed methods were readily
      applied to quantify GEC in seeds of 21 genotypes of V. narbonensis L. A good
      agreement between CE-MS and CE-UV results was observed corroborating the
      usefulness of both approaches for quantitative purposes.

PMID- 15966021
TI  - Protein adsorption in fused-silica and polyacrylamide-coated capillaries.
AB  - The model proteins cytochrome c, myoglobin, ovalbumin, and beta-lactoglobulin
      were investigated with regard to their adsorption properties on capillaries for
      electrophoresis. The model compounds were selected to cover a wide range of
      properties. Cytochrome c is a basic protein (isoelectric point (pI): 9.6; M(r):
      11.7 kDa), beta-lactoglobulin is rather acidic (pI: 5.4, M(r): 18.4 kDa),
      myoglobin was chosen as a neutral reference protein (pI: 6.8-7.4, M(r): 17.8
      kDa), and ovalbumin (pI: 5.1, M(r): 45.0 kDa) was selected as a relatively larger
      analyte. First, the pH dependence of adsorption was investigated for the bare
      fused silica. A clear correlation to the respective pIs was noted. For myoglobin
      and ovalbumin, none or negligible adsorption was found above the pI, whereas
      strong adsorption was noted just below this parameter. Cytochrome c and beta
      lactoglobulin already showed distinct adsorption above their pIs. However, none
      of the proteins showed any significant adsorption more than one pH unit above the
      pIs. For linear polyacrylamide-coated capillaries, a decreased but not a complete
      lack of adsorption was observed. Here, pH-dependent adsorption was noted as well.
      Regeneration of the capillaries by rinsing with buffers containing 200 mM SDS was
      also investigated. This method was completely successful for myoglobin, but that
      too for only freshly-adsorbed protein. After a storage time of 24 h and due to
      the aging of the adsorbate, a sufficient regeneration was no longer possible.

PMID- 15966022
TI  - "LaneSpector", a tool for membrane proteome profiling based on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis/liquid chromatography-tandem mass
      spectrometry analysis: application to Listeria monocytogenes membrane proteins.
AB  - Proteomics is required to provide insight into any type of subproteome. While the
      workflow based on two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
      can be applied for many subproteomes and comprises well-established strategies
      for data presentation and data analysis, the comprehensive investigation of
      membrane proteomes remains a challenging task. We present a number of procedures
      that provide an insight into such systems. We have established a novel protocol
      for the efficient preparation of membrane fractions, which is used here for the
      human pathogen Listeria monocytogenes that overcomes difficulties associated with
      ribosomes. Subsequently, we have used the combination of sodium dodecyl sulfate
      (SDS)-PAGE and liquid chromatography-tandem mass spectrometry for the
      characterization of the membrane proteome. Three hundred and one different
      membrane proteins could be identified, including 70 proteins that exhibited 2-15
      transmembrane domains. However, a remarkably high ratio of proteins was detected
      in gel sections that were not in accordance with their expected migration
      behavior during SDS-PAGE. Protein identifications based on MASCOT significance
      criteria could be shown to be of high quality and therefore could not be the
      explanation of this observation. Consequently we have developed LaneSpector, a
      general visualization tool that allows the systematic comparison between apparent
      and calculated protein masses, which is routinely applicable to any high
      throughput approach using a mass-dependent separation dimension prior to LC
      MS/MS. The detailed presentation of the LaneSpector plot promotes the validation
      of the analytical process and might help to reveal relevant biological processes
      such as proteolysis or other post-translational modifications.

PMID- 15966026
TI  - Pharmacokinetics of repinotan in healthy and brain injured animals.
AB  - Repinotan hydrochloride (repinotan) is a highly potent and selective 5-HT(1A)
      full receptor agonist. The ability of repinotan to cross the blood-brain barrier
      (BBB) and penetrate into rat brain tissue was investigated, because rapid
      penetration into brain tissue is thought to be essential for neuroprotective
      efficacy. Intravenous (i.v.) repinotan was rapidly distributed into brain, and
      the distribution equilibrium between blood and brain was reached immediately
      after the start of infusion. Free concentrations of repinotan were identical in
      brain and plasma, indicating that repinotan crosses the BBB freely in both
      directions with diffusion as a driving force. The brain concentration of
      repinotan was determined by the free plasma concentration. Thus, the total plasma
      concentration of repinotan (sum of bound and unbound compound) is only indicative
      for the brain concentration as long as the unbound fraction remains constant.
      Metabolites of repinotan do not penetrate the BBB and are retained in the
      perfusing blood due to their increased polarity. The penetration of [14C]
      repinotan into ischemic areas of the brain was dependent on time. In studies
      using injured animals (pMCAO), high levels of [14C] repinotan could be detected
      in ischemic areas when the compound was administered up to 5 h post injury. [14C]
      repinotan radioactivity could no longer be detected in ischemic areas when
      administered 18 h after pMCA-O. After the end of infusion, repinotan was rapidly
      and completely eliminated from rat brains. Elimination occurred in parallel from
      plasma and brain with half-lives of about 1 h. In conclusion, repinotan rapidly
      and to a considerable extent penetrates into brain tissue of healthy and injured
      animals.

PMID- 15966027
TI  - A microfabricated gas-liquid segmented flow reactor for high-temperature
      synthesis: the case of CdSe quantum dots.

PMID- 15966028
TI  - Synthesis and self-assembly of rod-rod hybrid poly(gamma-benzyl L-glutamate)
      block-polyisocyanide copolymers.

PMID- 15966029
TI  - High-spin molecules with magnetic anisotropy toward single-molecule magnets.
AB  - High-spin molecules with easy-axis magnetic anisotropy show slow magnetic
      relaxation of spin-flipping along the axis of magnetic anisotropy and are called
      single-molecule magnets (SMMs). SMMs behave as molecular-size permanent magnets
      at low temperature and magnetic relaxation occurs by quantum tunneling processes;
      such molecules are promising candidates for use in quantum devices. We first
      discuss intramolecular ferromagnetic interactions for preparing high-spin
      molecules. Second, we determine the magnetic anisotropy for single metal ions
      with d(n) configurations and discuss how molecular anisotropy arises from single
      ion anisotropy of the assembled component metal ions.

PMID- 15966030
TI  - Triplet acetylenes as synthetic equivalents of 1,2-bicarbenes, part II: new
      supramolecular scaffolds from photochemical cycloaddition of diarylacetylenes to
      1,4-cyclohexadienes.
AB  - 1,5-Diaryl substituted homoquadricyclanes which are readily available through
      cascade photocycloaddition of diarylacetylenes to 1,4-cyclohexadienes are useful
      supramolecular scaffolds with an angle of about 60 degrees formed by the two
      aromatic rings defining a hydrophobic cavity. These structural features of
      pyridinyl homoquadricyclanes were applied to the design of composite
      organic/inorganic materials with topologies depending on the ratio of ligand to
      metal. The crystal structure of complex 1 (L1/AgNO(3) in a 1:1 ratio) shows an
      alternating ligand-metal polymer in which each of the silver ions in its linear
      coordination geometry is shared between two L1 molecules. A small change in the
      crystallization method yields a supramolecular rhomboid (complex 2, L1/AgNO(3)
      3:2 ratio) which has two ligands that occupy opposite corners of the rhomboid and
      two silver atoms occupy the other two corners. Connection of the rhomboids units
      through a third molecule forms unique "beads on a string" polymeric chains. In
      complex 2, the silver ions adopt a distorted tetrahedral geometry with the
      nitrate anion occupying one of the vertices of the tetrahedron. The crystal
      packing of the chain of rhomboids generates cavities which are filled with
      disordered solvent molecules. Non-symmetrical homoquadricyclane L3 coordinates
      with silver only through the nitrogen of the pyridine ring but not through the
      nitrogen of the tetrafluoropyridine ring in which the electron density of the
      nitrogen lone-pair is very low. The substituents on the polycyclic moiety of the
      homoquadricyclane cause restricted rotation of the pyridine rings which suggests
      that the flexibility of such systems can be fine-tuned to create a family of
      supramolecular scaffolds of controlled rigidity.

PMID- 15966031
TI  - Two-component gel-phase materials--highly tunable self-assembling systems.
AB  - In the past 10 years, the molecular self-assembly and network formation of small
      molecule gelators has become one of the most active frontiers of the emergent
      area of nanochemistry. Increasingly, research efforts have begun to focus on
      multicomponent gelators, which rely on the initial interaction of distinct
      individual components to form a complex that subsequently self-assembles into a
      fibrous supramolecular polymer. In true two-component systems, an individual
      component can be present in isotropic solution, and only on addition of the
      second component will a gel actually form. In some cases, however, two-component
      gels are reported in which the second component significantly modifies the
      behaviour of a known gelator. Both systems are discussed in this article. The
      additional level of supramolecular control in the hierarchical self-assembly of
      two-component gels confers exquisite tunability and controllability.
      Functionality can be readily built into the material by simple variation of one
      of the individual components. This article discusses the key approaches used to
      control self-assembly by manipulating single molecular-recognition events and
      illustrates how controlling the transcription of information from the molecular
      to the macroscopic level by the simple addition of a second component allows
      complex functional materials to be selectively assembled from simple building
      blocks.

PMID- 15966032
TI  - Reversible absent/reversed end-diastolic flow in the umbilical artery, and
      reversible brain-sparing effect in a case with umbilical cord entanglement.

PMID- 15966033
TI  - The prenatal multiplier method for prediction of limb length discrepancy.
AB  - OBJECTIVE: The purpose of this study was to produce a method of predicting limb
      length discrepancy in utero. METHODS: Using available databases, we divided the
      femoral and tibial lengths at term by the femoral and tibial lengths at each week
      of gestation for each percentile. The quotients represent coefficients
      (multipliers) of limb segment growth at each prenatal age. RESULTS: We found the
      prenatal multipliers to be independent of race, percentile, and gender from as
      early as 12 weeks' gestation. The prenatal multipliers are alike for femur and
      tibia. CONCLUSIONS: The prenatal multiplier method allows for quick prediction of
      limb length discrepancy at term and at skeletal maturity from as early as 12
      weeks' gestation. Future study is needed to validate this method clinically.

PMID- 15966034
TI  - Osteogenesis imperfecta associated with first-trimester ventriculomegaly as an
      early ultrasound sign.

PMID- 15966035
TI  - Fetal lateral neck cysts: the significance of associated findings.
AB  - OBJECTIVES: The detection of fetal lateral neck cysts (FLNC) may create anxiety
      and confusion among pregnant woman and their physicians. We attempted to
      determine the incidence and significance of FLNC. Also, we tried to define the
      importance of the associated findings: the laterality of the finding, triple test
      results, maternal age and other ultrasonographic findings. METHODS AND MATERIALS:
      Between January 2000 and September 2003, 80 fetuses were evaluated at our
      institution for FLNC out of 3350 ultrasonic scans done for fetal malformations at
      14-16 weeks' gestation. RESULTS: The incidence of FLNC was 2.4% (80/3350). The
      majority of cases were isolated (53/80, 66%) and unilateral (46/80, 58%). Down
      syndrome was associated with nonisolated FLNC. CONCLUSION: Whether the finding
      was unilateral or bilateral had no significance. Associated increased nuchal
      translucency (NT) was of importance. Furthermore, the sole finding of increased
      NT is significant and the finding of the FLNC has no added value. There was no
      correlation between isolated FLNC without NT and fetal aneuploidy. However, other
      risk factors increase the risk for aneuploidy by up to 15 fold.

PMID- 15966036
TI  - Prospective audit of a one-centre combined nuchal translucency and triple test
      programme for the detection of trisomy 21.
AB  - OBJECTIVES: To determine detection and false-positive rates for trisomy 21 using
      two-stage combined nuchal translucency (NT) and triple testing, whilst disclosing
      abnormal nuchal measurements at the scan. METHODS: A prospective audit in a UK
      women's hospital, of 3188 women with singleton pregnancies, requesting screening
      for trisomy 21. Median age was 37 years (range 19-46). Women were offered NT
      screening at 11 to 14 weeks. Those with NT > or =3 mm were offered chorionic
      villus sampling. Those declining CVS, and those with NT <3 mm, were offered early
      triple tests. Women with a term combined risk of trisomy 21 > or = 1:250, based
      on age, NT, and triple test results were offered amniocentesis. RESULTS: Using a
      3-mm NT 'cut-off' identified 16/25 cases of trisomy 21 (64%; 95% CI 38.8, 78.9).
      Of 2725 women who had a combined nuchal plus triple test assessment, 79 (2.6%)
      had a > or = 1:250 term risk of trisomy 21. Forty (1.3%) had amniocentesis
      identifying 6/9 remaining cases (67%:95% CI:27.9, 92.5). Overall, the detection
      rate was 88% (95% CI:68.8, 97.5) for a 4.8% FPR. For the screened population, to
      achieve an 88% detection rate using the triple test alone, the predicted FPR
      would be 20%. Conversely, for an FPR of 4.8% using the triple test alone, the
      detection rate would be only 60%. CONCLUSION: In a high-risk group, the
      combination of NT with triple test offers detection of trisomy 21 at least
      equivalent to either test, while allowing disclosure of an abnormal NT at the
      scan and reducing the FPR. Importantly, the FPR is less than 5%, considerably
      lower than expected for triple test alone for this population.

PMID- 15966037
TI  - Prenatal diagnosis of partial trisomy 12q: clinical presentations and outcome.
AB  - We present a pregnant woman with a fetus prenatally diagnosed as 46, XY,der(4)
      t(4;12) (q35.1; q21.2). This defect resulted from the unbalanced segregation of a
      paternal balanced translocation, t(4;12) (q35.1; q21.2). Prenatal ultrasound
      revealed borderline ventriculomegaly, a thick nuchal fold, pericardial effusion,
      arthrogryposis, a single umbilical artery, and micropenis. Fluorescence in situ
      hybridization (FISH) with whole chromosome painting probe and microarray-based
      comparative genomic hybridization analysis further confirmed chromosomal gain of
      terminal 12q. The woman had her pregnancy terminated at 20 weeks of gestational
      age. When compared with previously reported cases, the proband had
      characteristics common to the phenotypes of partial trisomy 12q, including an
      abnormal facial appearance and multiple anomalies. Additionally, this case had
      previously unreported phenotypes, such as arthrogryposis, a single umbilical
      artery, and a micropenis. Regarding the outcome of partial trisomy 12q, the
      fetuses carrying trisomies distal to 12q24 have a good chance of extended
      postnatal survival. In contrast, the cases with trisomies involving a larger
      amount of 12q likely die prenatally or within a few days after birth.

PMID- 15966038
TI  - Sonographic features of lethal multiple pterygium syndrome at 14 weeks.
AB  - Lethal multiple pterygium syndrome is a rare inherited disorder. Previous reports
      suggest that the diagnosis may be based on prenatal sonographic demonstration of
      severe limb flexion, absence of fetal motion, and a large cystic hygroma in the
      second and third trimesters. We present the sonographic features and postmortem
      features of a fetus with lethal multiple pterygium syndrome at 13 weeks of
      gestation, which shows that the condition can possibly be diagnosed in the first
      trimester of pregnancy.

PMID- 15966039
TI  - First-trimester screening for fetal triploidy at 11 to 14 weeks: a role for fetal
      biometry.
AB  - OBJECTIVE: Intrauterine growth restriction in triploidy has been reported as
      early as in the first trimester. This study was undertaken to evaluate the
      ability of first-trimester crown rump length (CRL)-based charts to detect
      triploid fetuses. MATERIAL AND METHODS: Analysis of fetal biometry in cases of
      triploidy diagnosed in the first trimester over the last three years. Biometry
      for abdominal circumference (AC), head circumference (HC) and biparietal diameter
      (BPD) was analyzed in relation to both gestational age (GA)-based charts and to
      CRL-based charts. RESULTS: Five cases of fetal triploidy were diagnosed at 11 to
      14 weeks. Screening based on nuchal translucency (NT) and maternal age showed a
      risk > 1/300 in only one of the 5 cases of triploid fetus. In all of these five
      cases, CRL-based biometry was grossly abnormal, although it was abnormal in only
      two of these five cases in relation to GA-based charts. CONCLUSION: First
      trimester CRL-based biometry charts seem to reflect early asymmetrical growth
      delay in triploidy more accurately than GA-based charts. CRL-based biometry is
      likely to improve the early detection of triploid pregnancies without leading to
      dating error.

PMID- 15966040
TI  - Weight adjustment of serum markers in early first-trimester prenatal screening
      for Down syndrome.
AB  - OBJECTIVE: To assess whether existing weight correction formulas for PAPP-A and
      free-beta-hCG developed for weeks 11 to 14 can be applied to pregnancies in weeks
      8 to 10. METHODS: Development of formulas based on limited data sets of 8- to 10
      week pregnancies and comparison with existing formulas. Calculation of median
      MoMs adjusted with different formulas for weight correction. RESULTS: Weight
      correction formulas for the gestational age of 11 to 14 weeks were not
      appropriate in the 8- to 10-week gestational age interval for PAPP-A, whereas
      existing weight correction formulas could be applied to free-beta-hCG,
      independent of gestational age interval. CONCLUSION: If PAPP-A is used in
      different gestational age intervals, weight corrections should be developed for
      the interval.

PMID- 15966041
TI  - Perinatal findings of partial trisomy 13q (13q14.1-->qter) resulting from
      paternal pericentric inversion of chromosome 13.

PMID- 15966042
TI  - Frontal bilateral megalencephaly: fetal and autopsy MR evaluation of an
      unclassified malformation.
AB  - OBJECTIVE: To describe an unreported brain malformation with in utero onset.
      METHODS: A 21-weeks-of-gestational-age fetus underwent prenatal MR imaging
      because of macrocephaly detected by ultrasound. Prenatal MR imaging revealed a
      complex brain malformation. At 22 weeks of GA, pregnancy was terminated; an MR
      autopsy study was also performed. RESULTS: MR imaging revealed frontal bilateral
      megalencephaly and malformation of cortical development, suggesting
      polymicrogyria. These findings do not fit into any of the known megalencephalic
      syndromes. CONCLUSIONS: To our knowledge, this is a previously unreported
      malformation. Fetal and autoptic MR examination have been the best tools in
      understanding this complex brain pathology, allowing a more complete genetic
      counseling.

PMID- 15966043
TI  - Prenatal diagnosis in pregnancies at risk for Joubert syndrome by ultrasound and
      MRI.
AB  - OBJECTIVES: To describe the prenatal imaging findings in fetuses at risk for
      Joubert syndrome (JS), review the literature and propose a protocol for prenatal
      diagnosis of JS using ultrasound and MRI. METHODS: We reviewed prenatal
      ultrasound and fetal MRI studies in two pregnancies at 25% recurrence risk for JS
      and correlated these findings with gross neuropathology in one affected fetus.
      RESULTS: While abnormalities such as occipital encephalocele or enlarged cisterna
      magna have been identified before mid-trimester, the definitive diagnosis of JS,
      based on core cerebellar findings, has only been possible after 17 weeks'
      gestation. CONCLUSIONS: With longitudinal monitoring, it is possible to diagnose
      JS in at-risk pregnancies before 24 weeks' gestation. On the basis of our data
      and review of the literature, we propose a protocol for monitoring pregnancies at
      risk for JS, utilizing serial ultrasounds combined with fetal MRI at 20-22 weeks'
      gestation to maximize the accuracy of prenatal diagnosis.

PMID- 15966044
TI  - Prenatal diagnosis and molecular cytogenetic analysis of partial monosomy 10q
      (10q25.3-->qter) and partial trisomy 18q (18q23-->qter) in a fetus associated
      with cystic hygroma and ambiguous genitalia.
AB  - OBJECTIVES: To present the prenatal diagnosis and molecular cytogenetic analysis
      of a fetus with nuchal cystic hygroma and ambiguous genitalia. CASE AND METHODS:
      Amniocentesis was performed at 16 weeks' gestation because of the abnormal fetal
      sonographic finding of a large septated nuchal cystic hygroma. Genetic
      amniocentesis revealed a terminal deletion in the long arm of chromosome 10. The
      paternal karyotype was subsequently found to be 46,XY,t(10;18)(q25.3;q23). The
      maternal karyotype was normal. The pregnancy was terminated. A hydropic fetus was
      delivered with a septated nuchal cystic hygroma and ambiguous genitalia.
      Fluorescence in situ hybridization (FISH), microarray-based comparative genomic
      hybridization (CGH), and polymorphic DNA markers were used to investigate the
      involved chromosomal segments. RESULTS: FISH study showed absence of the 10q
      telomeric probe and presence of the 18q telomeric probe in the derivative
      chromosome 10. Microarray-based CGH analysis showed loss of distal 10q and gain
      of distal 18q. Polymorphic DNA marker analysis determined the breakpoints. The
      fetal karyotype was 46,XY,der(10)t(10;18)(q25.3;q23)pat. The chromosome
      aberration resulted in partial monosomy 10q (10q25.3-->qter) and partial trisomy
      18q (18q23-->qter). CONCLUSIONS: The present case provides evidence that partial
      monosomy 10q (10q25.3-->qter) with partial trisomy 18q (18q23-->qter) can be a
      genetic cause of fetal cystic hygroma and ambiguous genitalia. Cytogenetic
      analysis for prenatally detected structural abnormalities may detect unexpected
      inherited chromosome aberrations.

PMID- 15966045
TI  - Silver-Russell syndrome as a cause for early intrauterine growth restriction.
AB  - The diagnosis of Silver-Russell syndrome is based on the characteristic growth
      restriction and the presence of typical dysmorphic features. We present the
      prenatal and postnatal findings of a case that was treated at our perinatal
      center. The suspected diagnosis Silver-Russell syndrome was confirmed after
      delivery by our medical genetic and neonatology services. The authors want to
      point out that SRS should be considered in the differential diagnosis of early
      asymmetric intrauterine growth restriction.

PMID- 15966046
TI  - Prenatal diagnosis, sonographic findings and molecular genetic analysis of a
      46,XX/46,XY true hermaphrodite chimera.
AB  - OBJECTIVES: To present the prenatal diagnosis, sonographic findings and,
      molecular genetic analysis of a 46,XX/46,XY true hermaphrodite chimera and to
      review the literature. CLINICAL SUBJECT AND METHODS: Amniocentesis was performed
      at 22 weeks' gestation because of sonographic diagnosis of ambiguous genitalia.
      Initial amniocentesis, repeat amniocentesis, and cordocentesis revealed a mixture
      of 46,XX cells and 46,XY cells. Polymorphic DNA marker analysis using the fetal
      and parental blood was applied to investigate the genetic origin of the chimera.
      A 3,625-g baby was delivered at 37 weeks' gestation with clitoromegaly, prominent
      labia majora, fusion of the labia, and an orifice of the urogenital sinus. A
      lymphangioma was noted over the right arm and was excised at age 3 days.
      Extraembryonic tissues and the infant's skin were cytogenetically and molecularly
      studied. RESULTS: Initial amniocentesis, repeat amniocentesis, and cordocentesis
      revealed the karyotype of 46,XX[12]/46,XY[9], 46,XX[15]/46,XY[12], and
      46,XX[27]/46,XY[15], respectively. The cytogenetic results of the extraembryonic
      tissues and skin were consistent with prenatal diagnosis. Informative sex
      chromosome and pericentromeric autosome markers demonstrated double paternal and
      single maternal genetic contributions. CONCLUSIONS: Prenatal sonographic
      diagnosis of ambiguous genitalia should alert true hermaphroditism and prompt
      thorough genetic investigations. DNA marker analysis is helpful in delineation of
      true fetal chimerism as well as determination of its genetic origin in prenatally
      detected 46,XX/46,XY chromosome complement.

PMID- 15966047
TI  - Contribution of ultrafast magnetic resonance imaging in prenatal diagnosis of
      sonographically undetected cerebral tuberous sclerosis associated with cardiac
      rhabdomyomas.

PMID- 15966048
TI  - Prenatal magnetic resonance imaging of Galloway-Mowat syndrome.

PMID- 15966049
TI  - The effect of insecticide on adipokinetic hormone titre in the insect body.
AB  - The effect of an insecticide, permethrin (Ambush 25 EC), on the titre of two
      adipokinetic hormones in the central nervous system (CNS) and haemolymph of the
      firebug Pyrrhocoris apterus (L) was tested. Doses of 2.5, 12.5 and 25 ng of the
      insecticide elicited no significant effect on the titre of the adipokinetic
      peptides in CNS, but caused their dramatic elevation in the haemolymph of both
      macropterous and reproductive brachypterous bugs. Changes in diapausing
      brachypterous bugs were minimal and not significant. Using high-performance
      liquid chromatography (HPLC) and competitive ELISA, both adipokinetic peptides of
      P apterus (Pyrap-AKH and Peram-CAH-II) were identified and quantified in the CNS
      of all experimental groups. The ratios of the two peptides in the CNS of the bugs
      used were affected by insecticide treatment, but in all three groups of bugs the
      Pyrap-AKH level remained dominant. The insecticide-treated bugs were compared
      with those exposed to forced running (shaking) and dark shock. Both factors also
      acted as stressors and enhanced the titre of adipokinetic peptides in the
      haemolymph but had no effect on hormone titre in CNS. The results indicate an
      involvement of adipokinetic peptides in the response of insect to various
      stressors including insecticides.

PMID- 15966050
TI  - Which contingent sequential screening protocol?

PMID- 15966051
TI  - Chemiluminescent reaction of sulphite auto-oxidation in the presence of
      Ni(II)/tetraglycine and ruthenium(II)/bipy complexes: mechanistic considerations.
AB  - The present work is a mechanistic study of the possible analytical
      chemiluminescent reaction of sulphite oxidation in the presence of dissolved
      oxygen, Ni(II)/tetraglycine and [RuII(bipy)3]2+ ions. The Ni(III) complex
      oxidizes SO32- to SO3-, reacts with oxygen to produce SO5-, initiating a radical
      chain reaction. The strong oxidants generated oxidize Ni(II) and Ru(II) complexes
      in one redox cycle, which is related to the balance of SO32- and oxygen
      concentrations. The emission intensity depends on the concentrations of SO32-,
      Ni(II) and Ru(II) complexes.

PMID- 15966052
TI  - Analysis of the effect of a peptide sequence of the E2 protein (HGV/GBV-C) on the
      physicochemical properties of zwitterionic and negatively charged bilayers.
AB  - The membrane-interacting properties of a potential epitope of GB virus
      C/hepatitis G virus located at the region (99-118) of the E2 structural protein
      were investigated using several fluorescence techniques. SUV of DMPC:DPPC (1:1)
      or DMPG:DPPC (1:1) zwitterionic and anionic mixtures, respectively, were used as
      model membranes. FRET with NBD-PE as energy donor and Rho-PE as energy acceptor
      labelled SUV indicated that the peptide was able to fuse both zwitterionic and
      anionic SUVs, the latter requiring lower peptide concentrations. However, the
      peptide increased the steady-state anisotropy of DPH embedded in the hydrophobic
      centre of the membrane with zwitterionic headgroups and to a lesser extent in
      anionic bilayers, suggesting that charge-charge interactions are not required for
      membrane interactions and also confirming the FRET results. No changes in
      anisotropy were observed with the probe TMA-DPH located at the surface of the
      bilayer. Finally, analysis of the intrinsic emission fluorescence of the
      tryptophan residue, upon incubation with SUV, showed a blue shift in the presence
      of anionic bilayers, both below and above the main transition temperature (T(m))
      (gel to liquid-crystalline state) and, to a lesser extent, with the zwitterionic
      model membrane.

PMID- 15966053
TI  - Tetrabromohydroquinone and riboflavin are possibly responsible for green
      luminescence in the luminous acorn worm, Ptychodera flava.
AB  - 2,3,5,6-Tetrabromohydroquinone was isolated as a luminous substance from
      Ptychodera flava. This compound emitted light after addition of hydrogen peroxide
      under basic conditions. Since hydroquinone had no fluorescence, further
      investigation by spectral analysis revealed that riboflavin was the only possible
      light emitter having green fluorescence. In the presence of both
      tetrabromohydroquinone and riboflavin under a basic condition containing 70% 1,4
      dioxane, green light emission was observed following the addition of hydrogen
      peroxide. We succeeded in recording the same emission spectrum as that in the
      bioluminescence caused by the addition of aqueous diluted hydrogen peroxide
      solution in P. flava.

PMID- 15966054
TI  - Attempted cleaning of bloodstains and its effect on the forensic luminol test.
AB  - The forensic luminol test has long been valued for its ability to detect trace
      amounts of blood that are invisible to the naked eye. This is the first
      quantitative study to determine the effect on the luminol test when an attempt is
      made to clean bloodstained tiles with a known interfering catalyst (bleach).
      Tiles covered with either wet or dry blood were tested, and either water or
      sodium hypochlorite solution (bleach) was used to clean the tiles. As expected,
      the chemiluminescence intensity produced when luminol was applied generally
      decreased with the number of times that a tile was cleaned with water, until the
      chemiluminescence was neither visible nor detectable. However, when the tiles
      were cleaned with bleach there was an initial drop in chemiluminescence
      intensity, followed by a rise to a consistently high value, visibly
      indistinguishable from that of blood. Examination of bleach drying time suggested
      that any interfering effect becomes negligible after 8 h.

PMID- 15966055
TI  - Comparative study of antioxidants as quenchers or scavengers of reactive oxygen
      species based on quenching of MCLA-dependent chemiluminescence.
AB  - The quenching or scavenging effect of non-enzymatic antioxidants against reactive
      oxygen species (ROS) was studied by comparing the degree of suppression of
      chemiluminescence (CL) caused by the oxidation of MCLA (methoxylated Cypridina
      luciferin analogue) by ROS. MCLA-dependent CL caused by O2- was effectively
      quenched by ascorbic acid, beta-carotene, lycopene and astaxanthin, while it was
      enhanced by alpha-tocopherol. The CL by 1O2 was quenched effectively by beta
      carotene, lycopene and astaxanthin, moderately by ascorbic acid, and slightly by
      alpha-tocopherol. beta-Carotene and alpha-tocopherol remarkably suppressed the CL
      when ROS was HO*. The present study revealed that MCLA-dependent CL assay
      provides a simple and rapid method for the evaluation of antioxidants as a
      quencher or scavenger against any kind of ROS.

PMID- 15966056
TI  - Measurement of free and bound fractions of extracellular ATP in biological
      solutions using bioluminescence.
AB  - Measurement of extracellular ATP in biological solutions is complicated by
      protein-binding and rapid enzymatic degradation. We hypothesized that the
      concentration of extracellular ATP could be determined luminometrically by
      limiting degradation and measuring the free and protein-bound fractions. ATP was
      added (a) at constant concentration to solutions containing varying albumin
      concentrations; (b) at varying concentrations to a physiological albumin solution
      (4 gm/dL); (c) at varying concentrations to plasma. After centrifugation, a
      fraction of each supernatant was heated. ATP in heated and unheated samples was
      measured luminometrically. Blood was drawn into saline or an ATP-stabilizing
      solution and endogenous plasma ATP measured. ATP-albumin binding was a linear
      function of albumin concentration (3.5% ATP bound at 100 micromol/L to 33.2% ATP
      bound at 1000 micromol/L) but independent of ATP concentration (29.3%, 10-1000
      nmol/L ATP in 602 micromol/L albumin). Heating released the majority of bound ATP
      from albumin-containing solutions (94.8 +/- 1.7%) and plasma (97.6 +/- 5.1%).
      Total endogenous plasma ATP comprised 93 +/- 27 nmol/L (free) and 150 +/- 40
      nmol/L (total fraction). Without stabilizing solution, degradation of free
      endogenous plasma ATP occurred. Within a physiological range (10-1000 nmol/L),
      ATP binds albumin independently of ATP concentration. Heating releases bound ATP,
      enabling accurate luminometric measurement of total extracellular ATP (free and
      bound) in biological samples.

PMID- 15966057
TI  - Near-infrared chemiluminescence from the oxidation of ammonia in aqueous alkaline
      solution.
AB  - The chemiluminescent oxidation of ammonia with hypobromite in aqueous alkaline
      solution evokes a broadly distributed emission in the near-infrared region, with
      intensity maxima at 1055 nm and 1270 nm.

PMID- 15966058
TI  - Determination of methylmalonic acid in urine by HPLC with intramolecular excimer
      forming fluorescence derivatization.
AB  - We developed and validated an HPLC method with intramolecular excimer-forming
      fluorescence derivatization to determine methylmalonic acid, a unique biochemical
      marker for methylmalonic aciduria. Methylmalonic acid in urine and an internal
      standard were derivatized with pyrenebutyric hydrazide and separated on a C8
      column. The derivatives were detected by monitoring the fluorescence at 475 nm
      (excitation wavelength 345 nm). At a signal-to-noise ratio of 3, the detection
      limit was 0.33 pmol on the column and the calibration curve was linear up to 1
      mmol[sol ]L in urine. In a retrospective study on a relatively large number of
      known methylmalonic aciduria cases (n = 48), the method enabled us to
      differentiate methylmalonic aciduria cases from healthy controls (n = 52),
      regardless of age of patients at sampling or years of specimen storage. No
      interference was observed from isomeric or other dicarboxylic acids, or other
      urine constituents. As described, the method can be used retrospectively or
      prospectively for the diagnosis of methylmalonic aciduria and can be easily
      adopted by laboratories with no access to gas chromatography-mass spectrometry.

PMID- 15966059
TI  - 46,XY,18q+/46,XY,18q- mosaicism in a fragile X prenatal diagnosis.
AB  - OBJECTIVES: We describe a fetus with confined placental mosaicism for
      46,XY,dup(18)(q21q23)/46,XY, del(18)(q21) in which finally the 18q- cell line
      formed the embryo. This prenatal diagnosis was performed on a pregnant woman
      carrying a premutation in the FMR1 gene. The purpose of the current study was to
      characterise the final fetus genotype and to discuss how this chromosomal
      abnormality was originated. METHODS: Conventional cytogenetic analyses were
      performed from chorionic villi, amniocytes, and fetal blood samples in order to
      establish the fetal chromosome constitution. Molecular studies with
      microsatellite markers and CGH were carried out to this end. PCR and Southern
      blot were used to analyse the CGG-repeat region of the FMR1 gene. RESULTS: An
      initial chorionic villi sample analysis showed a normal allele for the fragile X
      syndrome, but an abnormal 46,XY,dup(18)(q21q23) karyotype. Amniocentesis was
      subsequently performed, and a different 46,XY,del(18)(q21) cell line was
      detected. Re-examination of original chorionic villi sample evidenced a mosaicism
      for 46,XY,dup(18)(q21q23)/46,XY,del(18)(q21). Molecular findings allowed us to
      determine that the deletion expands at least 20 Mb and that it is paternally
      inherited. CONCLUSION: Two different cell lines with structural abnormalities on
      chromosome 18 were formed as a consequence of an unequal sister chromatid
      exchange during the first post-zygotic division. This case reinforces the
      necessity of performing a karyotype in all prenatal diagnosis even when the
      indication is for a monogenic disease.

PMID- 15966060
TI  - Prenatal detection of a de novo terminal inverted duplication 4p in a fetus with
      the Wolf-Hirschhorn syndrome phenotype.
AB  - OBJECTIVES: To present the prenatal diagnosis of a de novo terminal inversion
      duplication of the short arm of chromosome 4 and a review of the literature.
      CASE: An amniocentesis for chromosome analysis was performed at 33 weeks'
      gestation because ultrasound examination showed a female fetus with multiple
      abnormalities consisting of severe intrauterine growth retardation, microcephaly,
      a cleft lip and renal hypoplasia. RESULTS: Cytogenetic analysis and FISH studies
      of the cultured amniocytes revealed a de novo terminal inversion duplication of
      the short arm of chromosome 4 characterized by a duplication of 4p14-p16.1
      chromosome region concomitant with a terminal deletion 4p16.1-pter. The karyotype
      was thus: 46,XX, inv dup del (4)(:p14-->p16.1::p16.1-->qter). The parents opted
      to terminate the pregnancy. Fetopathological examination showed dysmorphic
      features and abnormalities consistent with a Wolf-Hirschhorn syndrome (WHS)
      diagnosis, clinical manifestations of partial 4p trisomy being mild. CONCLUSION:
      Although relatively rare, inverted duplications have been reported repeatedly in
      an increasing number of chromosomes. Only two previous cases with de novo inv dup
      del (4p) and one with tandem dup 4p have been reported, all of them associated
      with a 4pter deletion. We report the first case diagnosed prenatally. Breakpoints
      are variable, resulting in different abnormal phenotype. In our case, clinical
      manifestations resulted in a WHS phenotype.

PMID- 15966061
TI  - Congenital cervical teratoma, associated with agenesis of corpus callosum and a
      subarachnoid cyst.
AB  - Cervical teratoma is a neoplasm composed of embryonic tissues with representation
      of all three germ layers. We report an extremely rare case of fetal cervical
      teratoma presenting at 24 weeks of gestation. A submaxillary mass and agenesis of
      corpus callosum were identified on ultrasonography, associated with agenesis of
      corpus callosum and a subarachnoid cyst.

PMID- 15966062
TI  - Fetal size charts for the Italian population. Normative curves of head, abdomen
      and long bones.
AB  - OBJECTIVE: To describe size charts developed from fetuses of Italian couples.
      METHOD: Prospective cross-sectional investigation conducted in three referral
      centers for prenatal diagnosis. The population of the study included fetuses
      between the 16th and the 40th week of gestation recruited prospectively and
      examined only once for the purpose of this study. Exclusion criteria comprised
      all maternal and/or fetal conditions possibly affecting fetal biometry. The
      following biometric variables were measured: biparietal diameter, head
      circumference, abdominal circumference, femur, tibia, humerus, ulna and radio
      length. The statistical procedure recommended for analyzing this type of data set
      was employed to derive normal ranges and percentiles. Birthweight was also
      recorded. Our centiles were then compared with results from other studies.
      RESULTS: The best-fitted regression model to describe the relationships between
      head circumference and abdominal circumference and gestational age was a cubic
      one, whereas a simple quadratic model fitted BPD, and length of long bones.
      Models fitting the SD were straight lines or quadratic curves. Neither the use of
      fractional polynomials (the greatest power of the polynomials being 3) nor the
      logarithmic transformation improved the fitting of the curves. CONCLUSION: We
      have established size charts for fetuses from Italian couples using the
      recommended statistical approach. Since the mean birthweight in this study is not
      statistically different from the official birthweight reported for the Italian
      population, these reference intervals, developed according to the currently
      approved statistical methodology, can be employed during second- and third
      trimester obstetric ultrasound of fetuses from Italian couples.

PMID- 15966063
TI  - My eye doctor told me that I'm at increased risk for retinal detachment. Can I
      reduce my risk?

PMID- 15966064
TI  - Are laxatives safe?

PMID- 15966065
TI  - Hope marks annual HIV vaccine awareness event.

PMID- 15966066
TI  - Prisons. Judge asked to drop contempt charge in HIV inmate suit.

PMID- 15966067
TI  - HIV and aging. More HIV survivors equates to more HIV-positive seniors.

PMID- 15966068
TI  - Disability life insurance benefits denied HIV-positive man.

PMID- 15966069
TI  - Prisons. HIV-positive inmate cannot design his own treatment.

PMID- 15966070
TI  - Criminal exposure. HIV-positive man jailed for nondisclosure.

PMID- 15966071
TI  - Synthesis, characterisation and cytotoxicity of chloro derivatives of
      prenylnaphthohydroquinone.
AB  - From the Diels-Alder adduct between alpha-myrcene and 2-chloro-1,4-benzoquinone,
      a family of chloro derivatives of prenylnaphthohydroquinone have been synthesised
      and evaluated for their cytotoxicity against 14 neoplastic cell lines.

PMID- 15966072
TI  - Pom: the new juice in town.

PMID- 15966073
TI  - Reassessing U.S. coral reefs.

PMID- 15966074
TI  - Reassessing U.S. coral reefs.

PMID- 15966075
TI  - Reassessing U.S. coral reefs.

PMID- 15966076
TI  - Reassessing U.S. coral reefs.

PMID- 15966077
TI  - Symposium for the future of cardiac surgery. Working Group Report. If retreat,
      how?

PMID- 15966078
TI  - Symposium for the future of cardiac surgery. Working Group Report. Integration of
      catheter-based techniques in cardiac surgery.

PMID- 15966079
TI  - An economist's analysis lacking common sense.

PMID- 15966080
TI  - A misconceived analysis of California's Health Insurance Act.

PMID- 15966081
TI  - The validity, reliability, reproducibility and extended utility of ankle to
      brachial pressure index in current vascular surgical practice.
AB  - BACKGROUND: Despite the increasing sophistication of vascular surgical practice,
      more than three decades after its introduction to clinical practice, the ankle to
      brachial pressure index (ABPI) remains the cornerstone of non-invasive assessment
      of the patient with symptomatic peripheral arterial disease (PAD). AIM: To
      summarise what is known about ABPI and critically appraise its validity,
      reliability, reproducibility and extended utility. METHODS: A MEDLINE (1966-2004)
      and Cochrane library search for articles relating to measurement of ABPI was
      undertaken; see text for further details. RESULTS: There is considerable
      disagreement as to how ABPI should be measured. Furthermore, various factors,
      including the type of equipment used, and the experience of the operator, can
      result in significant inter- and intra-observer error. As such, care must be
      taken when interpreting data in the literature. ABPI is valuable in the
      assessment of patients with atypical symptoms, venous leg ulcers and after
      vascular and endovascular interventions. However, absolute pressures are probably
      more valuable in patients with critical limb ischaemia. ABPI is also useful in
      subjects with asymptomatic PAD where it correlates well with, and may be used in
      screening studies to quantify, cardiovascular risk. CONCLUSIONS: While its
      apparent simplicity can beguile the unwary, ABPI will continue to have a key role
      in the assessment of symptomatic PAD. ABPI is also likely to have extended
      utility in health screening and institution of best medical therapy in
      asymptomatic subjects.

PMID- 15966082
TI  - Interpretation of the results of Doppler ultrasound flow volume measurements of
      infrainguinal vein bypasses.
AB  - OBJECTIVES: To evaluate a pattern for the interpretation of the results of
      intraoperative Doppler ultrasound flow volume measurement of infrainguinal vein
      bypasses. DESIGN: Retrospective analysis of prospective data. MATERIALS: 91
      consecutively performed infrainguinal non-reversed free vein bypasses. METHODS:
      Using preoperative angiograms, the run-off, which can be expected after the
      reconstruction, was evaluated by means of a point score. A first measurement of
      the flow volume was taken after the release of the blood flow and a second after
      administration of 20 mg Alprostadil into the bypass. From these two results, we
      calculated an average value, which was set in relation to the run-off score. From
      this we computed a relative flow, i.e. the flow per open crural vessel = per run
      off score unit (quotient:flow/score). RESULTS: The median relative flow of
      angiographically perfect reconstructions was 86 ml/min. In 14 reconstructions,
      the control angiogram showed stenoses: median relative flow 59 ml/min, range
      between 20 and a maximum of 75 ml/min. The practical application of the flow
      measurement requires a minimum relative flow guideline for stenosis-free
      reconstructions. A guideline of 80 ml/min would yield a sensitivity of 100% and a
      specificity of 68%. CONCLUSIONS: Measurement of flow volume could be used as a
      screen, in order to filter out reconstructions, which must be further clarified
      with an angiogram. A further prospective evaluation of the value of volume flow
      is needed before any conclusive recommendations can be drawn.

PMID- 15966083
TI  - End-to-end versus end-to-side distal anastomosis in femoropopliteal bypasses;
      results of a randomized multicenter trial.
AB  - OBJECTIVE: To compare end-to-side (ETS) and end-to-end (ETE) distal anastomoses
      for femoropopliteal bypasses. DESIGN: Prospective, randomized, multicenter trial.
      METHODS: Patients from 14 centers were randomized to either ETS or ETE distal
      anastomosis, with stratification according to center and four categories: venous
      and prosthetic above knee bypass, and venous and prosthetic below knee bypass.
      Follow-up, with history, physical examination, ankle-brachial pressure index and
      duplex scan was performed at 3 months, 6 months and every 6 months thereafter
      until 36 months postoperatively. RESULTS: A total of 328 femoropopliteal bypass
      operations were performed in 274 patients. Due to anatomical considerations at
      the time of surgery, 15 procedures (4.6%) were excluded from further analysis.
      Patient characteristics, cardiovascular risk factors, Rutherford classification
      and number of open run-off vessels were similar for both groups. Primary patency
      was 75 vs 74%, 65 vs 66% and 63 vs 55% for ETE vs ETS after 1, 2 and 3 years,
      respectively, (p = 0.26). During follow up major amputations were necessary in 20
      ETE bypasses and in nine ETS bypasses (p = 0.028). CONCLUSION: ETE distal
      anastomosis infemoropopliteal bypasses does not improve patency compared to ETS
      anastomosis. Major amputations, after failure of the bypass, were required more
      frequently for ETE distal anastomoses.

PMID- 15966084
TI  - Radiation therapy induced modulation of wound healing at experimental vein graft
      anastomoses.
AB  - OBJECTIVES: The aim of this study was to investigate if radiation therapy (RT)
      favorably modulates wound healing at vein graft anastomoses. MATERIALS AND
      METHODS: Jugular vein grafts were sewn into carotid arteries in 32 rats which
      were randomly divided into two groups: RT (gamma source, 14 Gray, n=16) and
      control (C, sham irradiation, n=16). Grafts and adjacent arteries were analyzed
      at 2 (n=8) and 8 weeks (n=8) by histology, immunohistochemistry, and morphometry.
      RESULTS: Although, RT did not reduce the overall occurrence of intimal
      hyperplasia, the distribution differed. RT led to a reduction of intimal
      hyperplasia in arterial segments (median: C: 41.873 microm2; RT: 6.452 microm2, p
      < 0.0007). In contrast, RT augmented intimal hyperplasia in vein grafts (median:
      C: 30.287 microm2; RT: 90.455 microm2, p < 0.014). Vein graft diameters after RT
      were enlarged (median: C: 2.098 microm; RT: 3.381, p < 0.031). Over 80% of the
      cells were of mesenchymal origin in both groups. CONCLUSIONS: RT reduced intimal
      hyperplasia in arterial segments. However, RT led to graft dilatation and
      increased intimal hyperplasia in vein grafts. RT did not favorably modulate the
      vascular wound healing response in this model.

PMID- 15966086
TI  - A review of the current treatment of renal artery stenosis.
AB  - PURPOSE: Atherosclerotic renal artery stenosis (ARAS) is associated with
      morbidity and mortality consequent to progressive ischemic renal failure and the
      cardiovascular consequences of hypertension. There is considerable uncertainty
      concerning the optimal management of patients with this condition. This review
      considers the aetiological factors and the physiologic consequences of ARAS and
      compares the results of clinical studies of medical and endovascular therapies on
      blood pressure control and preservation of renal function. RESULTS: Although, in
      patients with fibromuscular disease the results of percutaneous transluminal
      angioplasty (PTA) are clearly superior to medical therapy and surgery, in
      asymptomatic patients with ARAS the antihypertensive benefits and preservation of
      renal function of endovascular, surgical and medical therapies appear similar. In
      selected symptomatic patients interventions may, however, be life-saving. Surgery
      is generally reserved for arterial occlusions with preserved renal parenchyma and
      function. CONCLUSIONS: The results of larger, multicentre, randomised, controlled
      trials are required to clearly clarify the role of interventional therapy in
      asymptomatic patients.

PMID- 15966085
TI  - Activation of p38MAPK signaling cascade in a VSMC injury model: role of p38MAPK
      inhibitors in limiting VSMC proliferation.
AB  - INTRODUCTION: P38 mitogen-activated protein kinase (MAPK) has a crucial role in
      regulating signaling pathways implicated in the cellular events leading to
      restenosis. We examine p38MAPK activation in response to vascular cell injury,
      its biological effects and determine whether selective p38MAPK inhibitors,
      SB220025/SB203580, decrease vascular smooth muscle cell (VSMC) proliferation.
      METHODS: Human aortic VSMCs were cultured and wounds made on the monolayers to
      elicit mitogenic responses and induce p38MAPK activation. P38MAPK inhibitor
      pretreatment, at varying doses (1-100 microM) and treatment duration was used to
      block p38MAPK phosphorylation. Cytotoxicity, viability, proliferation and
      apoptosis were determined and expression of p38MAPK/phospho-p38MAPK was obtained
      by chemiluminiscent immunoblot analysis. RESULTS: Phosphorylation of p38MAPK
      depended on injury severity and was inhibited by both p38MAPK inhibitors, but not
      by SB202474, a specific antagonist of p38MAPK inhibitors. VSMCs treated with
      p38MAPK inhibitors showed a dose-dependent decrease in viable cell number,
      apoptosis and proliferation, reversing the deleterious effects of p38MAPK
      activation comparable to controls (p < 0.05). CONCLUSIONS: This wound injury
      model activates the p38MAPK-signaling cascade in VSMC and causes cell
      proliferation that can be abrogated by pre-incubation with p38MAPK selective
      synthetic inhibitors in a time and dose-dependent manner. SB220025 used here for
      the first time in VSMC reveals itself to be a stronger p38MAPK inhibitor than
      SB203580 and being a second generation inhibitor may be the preferred drug for
      novel therapeutic maneuvers.

PMID- 15966087
TI  - Elective open operation for abdominal aortic aneurysm in octogenarians--survival
      analysis of 105 patients.
AB  - OBJECTIVES: To study early mortality and long-term survival of patients more than
      80 years of age having elective open repair for abdominal aortic aneurysm (AAA).
      DESIGN: Retrospective multicenter cohort study. MATERIAL: One hundred and five
      patients, 23 women and 82 men, with a median age of 82 years, operated at three
      Norwegian hospitals during the period 1983-2002. METHOD: Survival analyses were
      based on data from medical records and the Norwegian Registrar's Office of Births
      and Deaths. Expected survival was based on mortality rates of the general
      population, matched by age, sex, and calendar period. Relative survival was
      calculated as the ratio between the observed and the expected survival. RESULTS:
      During the study period there has been a 10 fold increase in octogenarians
      treated with open operation for AAA. Early mortality (30-day) for the whole group
      of patients was 10.5% (95% confidence interval (95% CI) 5.3-18.0), and similar
      for both genders. The 5-year survival rate was 47% (95% CI 35.9-57.4), and not
      significantly different from that of a matched group in the general population.
      Patients aged 84 years or more had a median survival time of 35 months (95% CI
      18.5-51.6). CONCLUSION: The number of AAA operations in octogenarians has
      increased considerably during 20 years. Octogenarians operated electively for AAA
      has higher 30-day mortality as compared to younger patients. Their long-term
      survival appears similar to a matched control group. The benefit of surgery must
      be carefully considered against the perioperative risk, especially for the oldest
      octogenarians.

PMID- 15966088
TI  - Endovascular repair or surveillance of patients with small AAA.
AB  - OBJECTIVE: To compare the outcome of patients with small abdominal aortic
      aneurysms (AAA) treated in a prospective trial of endovascular aneurysm repair
      (EVAR) to patients randomized to the surveillance arm of the UK Small Aneurysm
      Trial. METHOD: All patients with small AAA (< or = 5.5 cm diameter) treated with
      a stent graft (EVARsmall) in the multicenter AneuRx clinical trial from 1997 to
      1999 were reviewed with follow up through 2003. A subgroup of patients
      (EVARmatch) who met the age (60-76 years) and aneurysm size (4.0-5.5 cm diameter)
      inclusion criteria of the UK Small Aneurysm Trial were compared to the published
      results of the surveillance patient cohort (UKsurveil) of the UK Small Aneurysm
      Trial (NEJM 346:1445, 2002). Endpoints of comparison were aneurysm rupture, fatal
      aneurysm rupture, operative mortality, aneurysm related death and overall
      mortality. The total patient years of follow-up for EVAR patients was 1369 years
      and for UK patients was 3048 years. Statistical comparisons of EVARmatch and
      UKsurveil patients were made for rates per 100 patient years of follow up (/100
      years) to adjust for differences in follow-up time. RESULTS: The EVARsmall group
      of 478 patients comprised 40% of the total number of patients treated during the
      course of the AneuRx clinical trial. The EVARmatch group of 312 patients excluded
      151 patients for age < 60 or > 76 years and 15 patients for AAA diameter < 4 cm.
      With the exception of age, there were no significant differences between
      EVARsmall and EVARmatch in pre-operative factors or post-operative outcomes. In
      comparison to the UKsurveil group of 527 patients, the EVARmatch group was
      slightly older (70 +/- 4 vs. 69 +/- 4 years, p = 0.009), had larger aneurysms
      (5.0 +/- 0.3 vs. 4.6 +/- 0.4 cm, p < 0.001), fewer women (7 vs. 18%, p < 0.001),
      and had a higher prevalence of diabetes and hypertension and a lower prevalence
      of smoking at baseline. Ruptures occurred in 1.6% of EVARmatch patients and 5.1%
      of UKsurveil patients; this difference was not significant when adjusted for the
      difference in length of follow up. Fatal aneurysm rupture rate, adjusted for
      follow up time, was four times higher in UKsurveil (0.8/100 patient years) than
      in EVARmatch (0.2/100 patient years, p < 0.001); this difference remained
      significant when adjusted for difference in gender mix. Elective operative
      mortality rate was significantly lower in EVARmatch (1.9%) than in UKsurveil
      (5.9%, p < 0.01). Aneurysm-related death rate was two times higher in UKsurveil
      (1.6/100 patient years) than in EVARmatch (0.8/100 patient years, p = 0.03). All
      cause mortality rate was significantly higher in UKsurveil (8.3/100 patient
      years) than in EVARmatch (6.4/100 patient years, p = 0.02). CONCLUSIONS: It
      appears that endovascular repair of small abdominal aortic aneurysms (4.0-5.5 cm)
      significantly reduces the risk of fatal aneurysm rupture and aneurysm-related
      death and improves overall patient survival compared to an ultrasound
      surveillance strategy with selective open surgical repair.

PMID- 15966089
TI  - Existing delays following the presentation of ruptured abdominal aortic aneurysm
      allow sufficient time to assess patients for endovascular repair.
AB  - OBJECTIVES: The greatest benefit of endovascular AAA repair (EVAR) may be in the
      management of rupture (RAAA). However, the detailed anatomical assessment
      required for EVAR has lead to concerns of surgical delay and death during cross
      sectional imaging. In this study, we prospectively assessed patients with RAAA
      and correlated time of hospital arrival with time of surgery or death to
      ascertain whether these concerns are justified. METHODS: All patients presenting
      with RAAA between October 2000 and December 2002 were included. The hospital
      arrival time, onset of surgery or time of death, were recorded, as were
      demographic and physiological parameters. RESULTS: One hundred consecutive
      patients were studied, median age 75 years (range 54-94). Seventy-nine patients
      underwent attempted conventional surgical repair and 21 were palliated. The
      median delay from arrival to operation was 159 min (range 16-1450 min). Mortality
      in the surgical group was not affected by the length of delay (p = 1.0) or by CT
      scanning (p = 0.34). The median time from arrival to death in the non-surgical
      group was 435 min (15 min-6 days). CONCLUSIONS: Most patients who present with
      ruptured AAA experience a significant delay prior to surgery. This study suggests
      it is safe to assess the majority of RAAA patients for EVAR.

PMID- 15966090
TI  - Endovascular treatment of acute abdominal aortic aneurysm with a bifurcated
      stentgraft.
AB  - OBJECTIVES: To analyse the results of emergency endovascular aneurysm repair
      (eEVAR) for acute abdominal aortic aneurysms (AAA), in comparison to open repair,
      and to evaluate suitability and application rate. PATIENTS AND METHODS: All
      patients treated for an acute AAA between January 1998 and August 2004 were
      included. The primary outcome measure was in-hospital mortality. Secondary
      outcome measures were procedure time, intra-operative blood loss, transfusion
      requirement, intensive care unit, and hospital length of stay. Suitability and
      application rate for eEVAR were assessed in a subgroup of patients, from January
      2003. RESULTS: A total of 253 patients were treated. eEVAR was performed in 40
      patients, 5 (13%) died in-hospital. Open repair was performed in 213 patients, 64
      (30%) died in-hospital. Secondary outcome measures were all significantly
      improved in the eEVAR subgroup. From January 2003, 56 patients were treated. Of
      the 44 (79%) patients who were evaluated for eEVAR, 16 (36%) patients were
      anatomically suitable. Eventually, 15 out of the 56 (27%) patients were treated
      by eEVAR. CONCLUSION: The results of eEVAR in a selected group of patients are
      promising, but suitability and application rate were low.

PMID- 15966091
TI  - Antithrombotic strategies in vascular surgery: evidence and practice.
AB  - BACKGROUND: The aim of this study was to evaluate the current practice of peri
      and postoperative antithrombotic therapy in vascular surgery in Austria and to
      compare this with the results of randomised prospective clinical trials. METHODS:
      A questionnaire assessing intra, postoperative and long-term antithrombotic
      treatment in 13 different surgical procedures (three supra-aortic, three aorto
      iliac reconstructions and seven inguinal and infra-inguinal arterial
      reconstructions) was sent to all 22 institutions training vascular surgical
      fellows in Austria. RESULTS: Intraoperative antithrombotic therapy was quite
      consistently performed with unfractionated heparin (UFH) with or without
      acetylsalicylic acid (ASA). Early and long-term postoperative therapy differed
      considerably. Most centres used low molecular weight heparin (LMWH) for early
      postoperative therapy after vascular reconstructions, in > 75% combined with ASA
      and/or clopidogrel. Long-term therapy consisted of antiplatelet agents in all
      centres. Vascular grafts were anticoagulated with UFH in 25% of the centres in
      the early postoperative period, the remaining institutions used LMWH +/-
      antiplatelet agents. For long-term antithrombotic therapy cumarins were used in
      75% of the centres, predominantly for venous grafts. Distal prosthetic grafts
      were mainly treated with antiplatelet agents. Intraoperative antithrombotic
      therapy was in accordance to present guidelines, postoperative antithrombotic
      therapy, however, differed considerably between the participating institutions
      and the results of available controlled studies. CONCLUSION: Optimal
      antithrombotic strategies during and after vascular surgery are still under
      debate, and current practice often differs from available evidence. Vascular
      surgical societies should be encouraged to define recommendations on antiplatelet
      therapy and anticoagulation for different vascular interventions.

PMID- 15966092
TI  - The benefits of combined anti-platelet treatment in carotid artery stenting.
AB  - OBJECTIVE: To assess the benefits of a combined anti-platelet regime of aspirin
      and clopidogrel in carotid artery stenting. METHODS: A randomised controlled
      trial was performed comparing aspirin and 24-h heparin with aspirin and
      clopidogrel for patients undergoing carotid artery stenting. Outcome measures
      included 30-day bleeding and neurological complications and 30-day stenosis
      rates. RESULTS: Bleeding complications (groin haematoma or excessive bleeding at
      the groin site) occurred in 17% of the heparin and 9% of the clopidogrel group
      (p=0.35; n.s). The neurological complication rate in the 24-h heparin group was
      25% compared to 0% in the clopidogrel group (p=0.02). The 30-day 50-100% stenosis
      rates were 26% in the heparin group and 5% in the clopidogrel group (p=0.10;
      n.s). CONCLUSIONS: The dual anti-platelet regime has a significant impact on
      reducing adverse neurological outcomes without an additional increase in bleeding
      complications. This study was terminated prematurely due to an unacceptable level
      of complications in the heparin arm of the trial.

PMID- 15966093
TI  - Fibrous cap thickness and smooth muscle cell apoptosis in high-grade carotid
      artery stenosis.
AB  - OBJECTIVE: There is growing evidence that, in high-grade internal carotid artery
      (ICA) stenosis, continuous fibrous cap thinning is not mandatory for plaque
      rupture and symptom development. The possibility that smooth muscle cell (SMC)
      apoptosis is involved in loss of fibrous cap volume has only been examined in a
      limited number of patients with high grade carotid artery stenosis. METHODS:
      Endarterectomy specimens from n = 38 consecutive patients undergoing surgery for
      high-grade ICA stenosis (> or = 70%) were transversely sectioned at 2 mm
      intervals. Plaque instability was defined clinically, by a history of recent
      ischemic symptoms (< 60 days before surgery; n = 19) attributable to the
      stenosis, or histopathologically by the presence of plaque rupture (n = 14).
      Detailed morphometric analyses of the fibrous cap was based on routine stains;
      for DNA in situ end labeling the TUNEL technique was used. SMCs were identified
      by immunostaining for SMC actin. RESULTS: We found no significant difference
      between symptomatic/asymptomatic or ruptured/unruptured plaque with respect to
      various morphometric measures of the fibrous cap (i.e. mean area, number of
      plaque sections with fibrous cap, necrotic core-to-lumen distance at its thinnest
      or thickest part). The mean (+/- SD) apoptotic SMCs per thousand within the
      fibrous cap was significantly higher in symptomatic vs. asymptomatic (64.53 +/-
      77.3 vs. 6.71 +/- 11.9; P<0.001) but not in ruptured plaques (43.3 +/- 64.4 vs.
      30.1 +/- 60.9; P=0.117). CONCLUSIONS: These data suggest that continuous thinning
      of the fibrous cap is not an essential prerequisite for plaque rupture in ICA
      stenosis. Symptomatic, but not ruptured plaque, were associated with the highest
      number of apoptotic SMC. Thus, it seems unlikely that SMC apoptosis promotes
      plaque rupture by fibrous cap thinning.

PMID- 15966094
TI  - First report of a new ultrasound velocity based system for atherosclerotic plaque
      characterisation.
AB  - PURPOSE: To built an experimental system that can create ultrasound velocity maps
      for human tissues. METHODS AND RESULTS: We describe a new experimental system and
      its use to examine ex vivo specimens of carotid atherosclerotic plaque.
      CONCLUSION: This new ultrasound system is promising but requires further testing
      and development in the laboratory.

PMID- 15966095
TI  - Late pseudoaneurysm following carotid patch infection.

PMID- 15966096
TI  - Laparoscopic ligation of the infrarenal vena cava in combination with
      transfemoral thrombin infusion: a new animal model of chronic deep venous
      thrombosis.
AB  - OBJECTIVE: We describe a new technique to create an animal model of chronic
      venous thrombosis. The morphological and histological properties of the resulting
      thrombi are described. METHODS: Thirteen pigs underwent laparoscopic ligation of
      the infrarenal vena cava in combination with transfemoral thrombin infusion.
      After 1, 3, 6, 9, 12 and 15 days, respectively, two animals were killed and the
      thrombosed vein segments were explanted. After recording their weight and
      dimensions, the thrombi underwent histological examination by light microscopy.
      RESULTS: In all 13 cases, the procedure was completed laparoscopically and all 13
      animals survived the procedure. While 12 pigs (92%) had an uneventful
      postoperative course, one animal died on the first postoperative night of an
      unknown cause. Autopsy revealed correct placing of the ligature with occlusive
      thrombosis of the inferior vena cava and the iliac veins in 12 animals, in one
      animal the ligature had been incorrectly placed around the origin of the right
      iliac vein with thrombosis limited to that vessel. Histological evaluation
      demonstrated mixed thrombi that showed increasing signs of organisation with
      advancing age. CONCLUSIONS: Laparoscopic ligation of the infrarenal vena cava in
      combination with transfemoral thrombin infusion is a safe and reliable way to
      produce chronic venous thrombosis in an animal model. The resulting thrombi are
      comparable to human deep venous thrombosis in terms of extent, size and
      organisation process.

PMID- 15966097
TI  - Leg ulceration in Portugal: prevalence and clinical history.
AB  - OBJECTIVE: To determine the prevalence and clinical history of leg ulceration in
      Portugal. DESIGN: Case identification of patients through health professionals
      providing care for patients with leg ulceration. SETTING: Clinical areas in
      hospital, community centres and patients' homes. PARTICIPANTS: Patients
      registered with five health centres within Lisbon suffering from ulceration of
      the leg receiving care from hospital and community staff. METHODS: Patients
      identified by health care professionals working in one area of Lisbon were asked
      to complete a simple proforma on each patient with leg ulceration. Patients were
      followed up prospectively to determine healing rates during this baseline period
      of evaluation. RESULTS: In total 263 patients were identified in a population of
      186,000 (total prevalence 1.41 (95%CI 1.25-1.59) per 1000 population). The
      prevalence was similar between men and women (1.3 and 1.46 per 1000,
      respectively). As expected this was highly age dependent being most common in the
      patients aged over 80 years (6.5 and 4.9 per 1000, respectively). Median duration
      of ulceration was 18 months, with 158/240 (66%) present for longer than 1 year,
      and 40 (17%) for longer than 5 years. The cause of ulceration was unknown to the
      health professional treating the patient in 86 (33%) patients. Diagnosis of
      aetiology was usually on the basis of clinical examination alone (145, 56%), with
      21 (8%) having undergone ankle to brachial pressure index (ABPI) measurements and
      a further eight undergoing either echo-Doppler or arteriography. Most care was
      provided by community services, with 145 (55%) treated in health centres and 77
      (29%) treated in the patient's home. CONCLUSIONS: The prevalence of chronic leg
      ulceration is similar to other reported studies in western Europe, and indicates
      that approximately 14,000 patients suffer from leg ulceration at any one time in
      Portugal. Leg ulceration causes a considerable burden on both hospital and
      community services.

PMID- 15966098
TI  - Phytochrome-controlled expression of a wheat Cab gene in transgenic tobacco
      seedlings.
AB  - We have monitored changes in the chlorophyll a/b-binding protein (Cab) mRNA
      levels in etiolated wheat leaves exposed to light of different wavelengths by
      Northern blot hybridizations and 5' S1 nuclease protection assays. Accumulation
      of the Cab mRNA and the specific Cab-1 transcript is regulated by phytochrome.
      Transcript levels are elevated by red light and the red enhancement can be
      partially reversed by far-red light. Moreover, far-red light alone can elicit a
      small increase in the transcript levels. These characteristic features of the
      wheat Cab-1 phytochrome response can be recapitulated in etiolated seedlings of
      transgenic tobacco containing the Cab-1 gene. Analyses of a chimeric construct
      revealed that a 1.8-kb 5'-flanking fragment (-1816 to +31) of the Cab-1 gene can
      confer phytochrome response as well as leaf-specific expression on a heterologous
      coding sequence.

PMID- 15966099
TI  - Meiotic segregation analysis of restriction site polymorphisms allows rapid
      genetic mapping.
AB  - The white rot fungus Phanerochaete chrysosporium is an efficient degrader of
      lignin. Development of classical genetics in this organism would require several
      years of work, so an alternative strategy was devised. As in the mapping of human
      genetic diseases, the approach depends on the presence of interallelic
      restriction site polymorphism, but differs in following their meiotic segregation
      into the haploid state. Using a set of 20 cloned sequences as probes we were able
      to demonstrate meiotic segregation of 14 restriction site polymorphisms from
      fruiting of a single dikaryotic culture and obtained evidence of genetic linkage
      within two groups of three and two of two. The method could be used to obtain a
      genetic map of this fungus and should be applicable to genetic analysis of any
      other organism for which haploid material is available.

PMID- 15966100
TI  - A 3.6-kbp segment from the vir region of Ti plasmids contains genes responsible
      for border-sequence-directed production of T region circles in E. coli.
AB  - The vir region of Ti plasmids is responsible for the transfer of the T region
      from Agrobacteria to plant cells; previous experiments suggested that formation
      of independent T region DNA circles is one step in this process. To study this
      step in Escherichia coli, we developed a binary vector system. One plasmid (=
      substrate) contains correctly oriented right and left borders from octopine
      plasmid pTiAch5. A gene with a counterselectable function (galK) was cloned
      between these borders. The galK gene is under control of the tac promoter
      operator and the lac repressor with the laci gene also in the selection cassette.
      This construction allows determination of substrate plasmid mutants which have
      lost the selectable galK function. The second component of the system is one of a
      set of compatible plasmids harbouring various cloned parts from the vir region of
      nopaline plasmid pTiC58. A 3.6-kbp segment of the vir region turned out to be
      necessary and sufficient for production of substrate plasmid mutants which
      represented the equivalent of the T region containing a complete left border.
      From this vir region fragment four discrete proteins were expressed in minicells.
      The coding regions were mapped to a part conserved in nopaline and octopine
      plasmids; in the latter it appears to correspond to virC/D.

PMID- 15966101
TI  - Overdrive, a T-DNA transmission enhancer on the A. tumefaciens tumour-inducing
      plasmid.
AB  - During crown gall tumorigenesis a specific segment of the Agrobacterium
      tumefaciens tumour-inducing (Ti) plasmid, the T-DNA, integrates into plant
      nuclear DNA. Similar 23-bp direct repeats at each end of the T region signal T
      DNA borders, and T-DNA transmission (transfer and integration) requires the right
      hand direct repeat. A chemically synthesized right border repeat in its wild-type
      orientation promotes T-DNA transmission at a low frequency; Ti plasmid sequences
      which normally flank the right repeat greatly stimulate the process. To identify
      flanking sequences required for full right border activity, we tested the
      activity of a border repeat surrounded by different amounts of normal flanking
      sequences. Efficient T-DNA transmission required a conserved sequence (5'
      TAAPuTPy-CTGTPuT-TGTTTGTTTG 3') which lies to the right of the two known right
      border repeats. In either orientation, a synthetic oligonucleotide containing
      this conserved sequence greatly stimulated the activity of a right border repeat,
      and a deletion removing 15 bp from the right end of this sequence destroyed it
      stimulatory effect. Thus, wild-type T-DNA transmission required both the 23-bp
      right border repeat and a conserved flanking sequence which we call overdrive.

PMID- 15966102
TI  - The 'light' and 'medium' subunits of the photosynthetic reaction centre from
      Rhodopseudomonas viridis: isolation of the genes, nucleotide and amino acid
      sequence.
AB  - The 'light' (L) and the 'medium' (M) subunits of the photosynthetic reaction
      centre from Rhodopseudomonas viridis were isolated and their amino-terminal
      sequences, as well as the sequences of several chymotryptic peptides, determined.
      Rps. viridis DNA was cloned in the Escherichia coli plasmid pBR322. Mixed
      oligonucleotide probes derived from the amino acid sequences were synthesized and
      utilised to isolate one clone which contained the genes for the L and M subunits
      of the reaction centre as well as the alpha and beta subunits of the light
      harvesting complex and part of the gene for the reaction centre cytochrome. The
      nucleotide sequences of the L and M subunit genes and teh derived amino acid
      sequences are presented. The L subunit consists of 273 amino acids and has a mol.
      wt of 30 571. The M subunit consists of 323 amino acids and has a mol. wt of 35
      902. The primary structure is discussed in the light of the recently published
      secondary and tertiary structure which has shown that both subunits contain five
      membrane-spanning helices.

PMID- 15966103
TI  - Second gene (nifH*) coding for a nitrogenase iron protein in Azotobacter
      chroococcum is adjacent to a gene coding for a ferredoxin-like protein.
AB  - Azotobacter chroococcum MCD1 contains a cluster of nitrogen fixation (nif) genes
      coding for the structural polypeptides for nitrogenase (nifH for the Fe-protein
      and nifD and nifK for the MoFe protein) and a second sequence in the genome
      homologous to nifH. DNA fragments bearing this second nifH-like sequence were
      cloned and the DNA sequence around the homologous region determined. Two open
      reading frames were identified in this region. One codes for a protein of 289
      amino acid residues and is highly homologous to other Fe-proteins but is
      different from the gene adjacent to the nifDK genes in A. chroococcum. This
      putative gene we call nifH*. The following open reading frame codes for a protein
      of 63 amino acids, nine of which are cysteine residues. The protein is homologous
      to the small low-potential ferredoxins found in anaerobic bacteria, and in
      particular those from Chlorobium limicola. Linkage between a structural gene for
      nitrogenase and a small ferredoxin has not previously been observed. Sequence
      analysis suggests that the two genes form an operon. Transcription of the
      ferredoxin gene on a 1320-bp transcript was only detectable under conditions in
      which A. chroococcum MCD1155, which carries a chromosomal deletion of 6.3 kb
      removing the entire nifHDK cluster, is capable of fixing N2, i.e. in media
      containing no added molybdenum or high levels of NH3. The size of the observed
      transcript agrees well with the predicted size for a transcript encoding nifH*
      and the ferredoxin genes. Expression of the nifH* promoter was not significantly
      activated in Escherichia coli even when nifA, the positive activator of nif genes
      in Klebsiella pneumoniae, was supplied in multiple copies. The results are
      discussed in relation to an alternative pathway for N2 fixation in A.
      chroococcum.

PMID- 15966105
TI  - The spread of HIV in Africa.
AB  - A significant effort has been put into identifying the origin of HIV, tracking
      its spread, and mapping its distribution. This effort is of particular importance
      in Africa, where the AIDS epidemic is genetically most diverse, where prevalence
      reaches its highest levels, and where HIV had its origins in cross-species
      transmission from non-human primates to man. In this article, we summarize the
      molecular epidemiology of HIV in Africa, from both a historical and modern
      perspective. There are marked differences in the local diversity and in the rate
      of epidemic expansion in different regions of Africa. Understanding the
      distribution of genetic forms of HIV can be used to tailor vaccine strategies to
      specific regions and nations. Finally, we review the relationship of HIV lineages
      to related simian retroviruses and the evolutionary history and the origins of
      the HIV epidemic.

PMID- 15966104
TI  - The pleiotropic nature of symbiotic regulatory mutants: Bradyrhizobium japonicum
      nifA gene is involved in control of nif gene expression and formation of
      determinate symbiosis.
AB  - In the slow-growing soybean symbiont, Bradyrhizobium japonicum (strain 110), a
      nifA-like regulatory gene was located immediately upstream of the previously
      mapped fixA gene. By interspecies hybridization and partial DNA sequencing the
      gene was found to be homologous to nifA from Klebsiella pneumoniae and Rhizobium
      meliloti, and to a lesser extent, also to ntrC from K. pneumoniae. The B.
      japonicum nifA gene product was shown to activate B. japonicum and K. pneumoniae
      nif promoters (using nif::lacZ translational fusions) both in Escherichia coli
      and B. japonicum backgrounds. In the heterologous E. coli system activation was
      shown to be dependent on the ntrA gene product. Site-directed insertion and
      deletion/replacement mutagenesis revealed that nifA is probably the promoter
      distal cistron within an operon. NifA- mutants were Fix- and pleiotropic: (i)
      they were defective in the synthesis of several proteins including the nifH gene
      product (nitrogenase Fe protein); the same proteins had been known to be
      repressed under aerobic growth of B. japonicum but derepressed at low O2 tension;
      (ii) the mutants had an altered nodulation phenotype inducing numerous, small,
      widely distributed soybean nodules in which the bacteroids were subject to severe
      degradation. These results show that nifA not only controls nitrogenase genes but
      also one or more genes involved in the establishment of a determinate, nitrogen
      fixing root nodule symbiosis.

PMID- 15966107
TI  - Salivary excretion of rabies virus by healthy vampire bats.
AB  - Salivary excretion of rabies virus was evaluated in 14 adult vampire bats
      (Desmodus rotundus) intramuscularly injected with a large dose (10(6) MICLD50) of
      vampire rabies virus variant CASS88. Saliva samples were obtained from surviving
      bats every other day for 30 days, then weekly for 2 months, and finally 1 and 2
      years later. Rabies virus was isolated in murine neuroblastoma cells and in
      randomly selected cases by PCR. Rabies virus was not detected in the saliva of
      any of the 11 animals that succumbed (somewhat early) to rabies challenge, nor in
      the control bats. In contrast, virus was detected early, and only once (days 6, 6
      and 21) in each of the three animals that survived rabies challenge and remained
      healthy for at least 2 years after challenge. At that time even vigorous
      dexamethasone and cyclosporine administration failed to provoke further viral
      excretion.

PMID- 15966108
TI  - Performance on the CERAD neuropsychology battery of two samples of Japanese
      American elders: norms for persons with and without dementia.
AB  - Norms for cognitive measures used to assess dementia are scant for minority
      groups, in particular for older Japanese Americans. Using the Consortium to
      Establish a Registry for Alzheimer's Disease (CERAD) Neuropsychology Battery, we
      compared the baseline performance of demented and nondemented Japanese Americans.
      Participants came from two harmonized epidemiological studies of dementia which
      were examined separately: the Kame Project, Seattle (350 men and women; 201
      nondemented), age 65 and older; Honolulu-Asia Aging Study (HAAS), Hawaii (418
      men; 120 nondemented), age 71 and older. The measures examined were Verbal
      Fluency; abbreviated Boston Naming; constructional praxis; and Word List
      Learning, Recall, and Recognition. Within each study, the CERAD measures
      distinguished between nondemented participants and those with mild cognitive
      impairment. Among persons with dementia, average level of performance decreased
      as severity of dementia increased. Determinants of score (age, education,
      language of administration, stage of dementia) varied between the two studies.
      Among Japanese Americans, the CERAD Neuropsychology Battery distinguished
      nondemented persons from those with dementia, but was less consistent in
      distinguishing levels of severity of dementia. This battery is useful for
      comparative epidemiological studies of dementia in minority populations.

PMID- 15966106
TI  - In vitro methods in the study of viral and prion permeability across the blood
      brain barrier.
AB  - (1) Infectious agents capable of entering the central nervous system (CNS)
      produce some of the most dreaded diseases known to man. The infectious agent
      within the CNS is often protected by the blood-brain barrier (BBB), shielded from
      endogenous and exogenous anti-infectious agents. (2) The use of in vitro methods
      offers many advantages to the study of how infectious agents interact with the
      BBB. Two such agents which negotiate the BBB early in the course of disease
      before damage to the BBB are the autoimmune deficiency syndrome virus, or human
      immunodeficiency virus 1, and scrapie prion. Our laboratories have used in vitro
      methods to study these agents. (3) Here, we review some of the results form our
      laboratories and those of others.

PMID- 15966109
TI  - Delayed cell death and bystander effects in the progeny of Chinook salmon embryo
      cells exposed to radiation and a range of aquatic pollutants.
AB  - PURPOSE: To determine whether delayed and bystander effects can be seen in both a
      non malignant teleost fish cell line, (CHSE) and a malignant teleost fish cell
      line (EPC) when exposed to low doses of ionising radiation and genotoxic
      pollutants. METHODS: Teleost fish cells were briefly exposed to radiation and
      chemical toxins at low doses. Clonogenic survival was measured in the exposed
      population and the distant progeny of exposed cells to assess early and delayed
      cell death. Clonogenic survival was also measured in cultures, which received
      medium from briefly exposed cells to determine bystander effects. RESULTS: The
      dose response pattern for both early and delayed cell death was found to differ
      for different stressors. Different mechanisms of cell death appear to be involved
      in the early cytotoxic effect and the delayed effect. No delayed cell death
      occurred in a transformed fish cell line (EPC). Bystander effects occurred in
      CHSE cells and were similar in intensity to previously reported mammalian cell
      bystander effects. CONCLUSIONS: The results may have implications for radiation
      and environmental protection of biota. They demonstrate that damage caused by low
      doses of radiation and common aquatic pollutants is not only similar but occurs
      in both acute and delayed forms.

PMID- 15966110
TI  - Temperature effects on development and survival of two stable flies, Stomoxys
      calcitrans and Stomoxys niger niger (Diptera: muscidae), in La Reunion Island.
AB  - Two stable fly species, Stomoxys calcitrans (L., 1758) and Stomoxys niger niger
      Macquart, 1851, co-occur in La Reunion, where they are important pests of cattle.
      The survival and developmental rate of the immature stages were compared at five
      constant temperatures from 15 to 35 degrees C. In both species, immature survival
      was highest at 20-25 degrees C and markedly decreased at 15 and 35 degrees C. At
      the lower temperatures, mortality was observed mainly for S. calcitrans larvae
      and S. niger eggs. At the higher temperatures, mainly pupae of both species died.
      At all temperatures, S. calcitrans survived better than S. niger. Developmental
      time was highly similar in both species, decreasing from 71 d at 15 degrees C to
      13 d at 30 degrees C in S. calcitrans and from 69 d at 15 degrees C to 14 d at 30
      degrees C in S. niger. Developmental times increased slightly at 35 degrees C.
      Surprisingly, the tropical S. niger developed slightly faster than the
      cosmopolitan S. calcitrans at 15-20 degrees C; the reverse was found at higher
      temperatures. Temperature summation models confirmed that S. niger had a lower
      developmental threshold than S. calcitrans (11.3 versus 12.2 degrees C) and
      higher day-degree (DD) requirements to complete development (251 versus 225 DD).
      Overall, the results suggest that S. calcitrans is better adapted than S. niger,
      in terms of adult production from eggs, in the temperature range of La Reunion.

PMID- 15966111
TI  - Utility of the MacArthur-Bates communicative development inventory in identifying
      language abilities of late-talking and typically developing toddlers.
AB  - The present study investigated the validity of the MacArthur-Bates Communicative
      Development Inventory (CDI) for a group of toddlers 30 months of age. Study 1
      examined the concurrent validity of the CDI for a group of 38 late talkers.
      Significant correlations were found between the CDI and direct measures of
      language abilities. Study 2 used likelihood ratio analysis to determine how well
      the CDI sorted 100 toddlers (38 late talkers and 62 children with a history of
      normal language development) according to language status based on direct
      assessment measures. The analyses showed that the CDI was effective in
      identifying children with low language skills up to the 11th percentile and in
      identifying children with normal language skills above the 49th percentile.

PMID- 15966112
TI  - Sources of emotional help sought by low income women of Mexican descent.
AB  - From a larger convenience sample of 315 women of Mexican descent, the focus of
      this secondary analysis of cross sectional data was a subset of 68 women who
      reported that they sought help for feelings of sadness, hopelessness, or
      depression within the last year Women who sought help from professional sources
      had significantly higher depressive (CES-D) and PTSD (IES-R) symptoms than women
      who sought help from "other or multiple" sources that included friends. Women who
      sought help exclusively from family or from professionals scored over the CES-D
      and IES-R cutpoints. Results are useful for designing future research on help
      seeking preferences of Latina women.

PMID- 15966113
TI  - [What is the specificity for the animal models of psychiatric disorders?].

PMID- 15966114
TI  - [Diogenes syndrome: a diagnostic approach].

PMID- 15966115
TI  - Illinois pharmacist sues over contraceptive rule.

PMID- 15966116
TI  - Hodgkin's returns to girl whose parents fought state: standoff ends as court
      hears test results.

PMID- 15966117
TI  - It's not so easy to adopt an embryo.

PMID- 15966118
TI  - U.S. to review drug intended for one race.

PMID- 15966119
TI  - Italian vote to ease fertility law fails for want of voters.

PMID- 15966120
TI  - Implants with flaws: disclosure and delay.

PMID- 15966121
TI  - Justices expand rights to experiment with patented drugs.

PMID- 15966122
TI  - Mundane misdeeds skew findings, researchers say.

PMID- 15966123
TI  - Playing God with birth defects in the nursery.

PMID- 15966124
TI  - After horrific burn, a wife's choice: is treatment wise? Artificial skin for Ted
      Fink meant pain and risks; a 7-month induced coma; 'I really didn't want to
      look'.

PMID- 15966125
TI  - Worrisome ailment in medicine: misleading journal articles; editors demand more
      data to ensure full disclosure of drug risks, trial gaps; Sarbanes-Oxley for
      professors.

PMID- 15966126
TI  - Negotiating the terms of your death: medical advances give patients more control
      over how and when they die.

PMID- 15966127
TI  - Stem-cell lines.

PMID- 15966128
TI  - Abstracts of the 3rd United Kingdom Radiation Oncology Conference (UKRO). 11-13
      April 2005, University of York, United Kingdom.

PMID- 15966129
TI  - Medical editor turns activist on drug trials.

PMID- 15966130
TI  - Retraction: article on estrogen receptor beta in ovarian carcinogenesis.

PMID- 15966131
TI  - Role of combination inhaled corticosteroids and long acting beta agonists in the
      treatment of adult asthma.
AB  - An inhaled corticosteroid (ICS) and a long acting beta agonist (LABA) are
      combined in an inhaler for treatment of persistent asthma. There is evidence that
      maintenance therapy with a combination ICS/LABA inhaler improves clinical
      outcomes and reduces airflow obstruction in patients with persistent asthma, who
      are not well controlled even when using ICS maintenance therapy. There is
      evidence that a combination ICS/LABA inhaler may also play a role in initial
      maintenance therapy for patients with mild persistent asthma, who have never used
      ICS therapy. There is no evidence regarding the use of combination therapy in
      intermittent asthma. Oral candidal infections, hoarseness and pharyngolaryngeal
      pain are the most frequently reported adverse events. Combination inhaler therapy
      can improve compliance with guidelines that recommend a LABA only be used with
      concurrent ICS administration.

PMID- 15966132
TI  - Automated external defibrillators for home use.
AB  - The Philips HeartStart Home Defibrillator is an automated external defibrillator
      (AED) that is approved for home use by untrained users. Most cardiac arrests
      occur in the home, so a rapid response with cardiopulmonary resuscitation (CPR)
      and defibrillation is critical for survival. No prospective studies demonstrate
      that the use of AEDs in the home by untrained persons improves health outcomes.
      Further investigation is needed to determine the benefit and harm of AEDs in the
      home.

PMID- 15966133
TI  - Anti-Mi-2 antibodies.
AB  - Autoantibodies targeting the Mi-2 nuclear antigen represent one of the serologic
      hallmarks of idiopathic inflammatory myopathies, with a diagnostic sensitivity
      and specificity of approximately 4-18% and 98-100%, respectively. Mi-2 antigen is
      a component of the nuclesome remodeling-deacetylase (NuRD) complex involved in
      transcription regulation.Anti-Mi-2 antibodies are strongly associated with
      dermatomyositis (frequency up to 31%) and have a very high positive predictive
      value for such disease subset. A strong correlation with HLA-DR7 has been
      demonstrated. At the moment, optimal serologic testing is achieved by ELISA
      screening on recombinant Mi-2 antigen and confirmation of positive results on
      immunoblot.

PMID- 15966134
TI  - Patent news.

PMID- 15966135
TI  - Licensing highlights.

PMID- 15966136
TI  - War and peace in the new year.
AB  - The world has been turned upside down and changes are being forced on society
      from unexpected directions. It is an opportune time to consider the changes that
      are likely to be witnessed in the medical technology sector.

PMID- 15966137
TI  - Outsourcing manufacturing.
AB  - In addition to increasing their technical ability, some contract manufacturers
      are expanding the capacity of their operations by 20% per year. This article
      outlines how to capitalise on this trend and successfully move a manufacturing
      operation to a contract manufacturer.

PMID- 15966138
TI  - Supplying the health-care explosion.

PMID- 15966139
TI  - Implantable microsystems for monitoring and neural rehabilitation, part I.
AB  - Miniaturised implantable biomedical microsystems are offering completely new
      product possibilities for diagnosis and therapy. Some of the latest developments
      are discussed here. Part I of this two-part article describes microdevices for
      diagnosing and monitoring blood, brain and intraocular pressure inside the body,
      and a retina implant system.

PMID- 15966140
TI  - Development of a device for rapid diagnosis of Down's syndrome.

PMID- 15966141
TI  - The Center for Devices and Radiological health: an update.
AB  - At a recent medical device conference, Dr. David Feigal, the Director of the Food
      and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH)
      stated that one-third of the CDRH staff will retire in five years. This is only
      one of many challenges that the Center faces.This article discusses key factors
      shaping current FDA device policies and programmes, the CDRH strategic plan, the
      continuing importance of the standards programme, and CDRH harmonisation
      activities.

PMID- 15966142
TI  - Reflections on the year.

PMID- 15966143
TI  - The standards year: how things went in 2001.

PMID- 15966144
TI  - How to select a sterilisation process.
AB  - The decision on how to sterilise a medical device is dependant on many factors
      and as a result requires detailed investigation early in a project. The key
      factors are which processes are compatible with the materials and packaging used
      for the product. Other critical factors are cost, speed, the availability of a
      technology and level of customer support that is provided.

PMID- 15966145
TI  - Giving the industry a face.

PMID- 15966146
TI  - Validation.
AB  - Validation is often considered to be a complex process that is arduous to
      implement. This article describes recommended validation techniques and answers
      frequently asked questions on how to validate machines and processes.

PMID- 15966147
TI  - Costs concerns keep more sick Americans from needed meds. Those with chronic
      conditions are particularly at risk.

PMID- 15966148
TI  - States, employers tussling in coverage tug-of-war. 'Wal-Mart laws' typify messy
      debate as to who has responsibillity for providing coverage.

PMID- 15966149
TI  - Rate hike delays long-term care debate--for now. CMS boosts SNF rates, but
      tougher decisions await.

PMID- 15966150
TI  - States consider unprecedented number of Rx drug laws. Reimportation, Medicare
      part D affecting agendas across country.

PMID- 15966151
TI  - Navigating the waters of pharmacy regulations in hospice care. Facing a common
      scenario: why can it be so difficult to obtain emergency medications?
AB  - Imagine a common scenario that faces many hospice clinicians: It is 1 a.m., and
      the sister of your newest patient just called the on-call service to alert your
      hospice that the patient is in excruciating pain. In fact, the patient's pain is
      so bad that she is asking whether she should take her to the nearest hospital
      emergency room. You anticipated this pain, of course, but the patient did not
      have moderate or severe pain to this point, and the physician wouldn't agree to
      provide a small supply of morphine to have on hand.

PMID- 15966152
TI  - Congressman Greg Walden speaks out in support of home care.
AB  - Support for the mission of home care and hospice from Congress continues to
      expand as more members of the House and Senate take time out of their busy
      schedules to visit with a home care or hospice patient. Take the case of
      Congressman Greg Walden (R-OR) who is currently in his fourth term representing
      the people of Oregon's Second Congressional District, which includes twenty
      counties in central, southern and eastern Oregon. He is a passionate advocate for
      home care and hospice who as chair of the Congressional Rural Health Care
      Coalition, is a key figure in the fight to restore the 5% rural add on for home
      health services to rural patients.

PMID- 15966153
TI  - Exclusive...an interview with Greg Walden. Interview by Val J. Halamandaris.
AB  - In this article, Walden discusses the attributes a strong leader must have, whom
      he holds up as his own role models, and how one person can make a difference in
      this life. Halamandaris' probing questions bring insight for the reader about the
      values the congressman holds in high regard, and his commitment to improving the
      delivery of health care in America, particularly to those in rural areas.

PMID- 15966154
TI  - Lessons from Schiavo beyond the legal.
AB  - Our nation has faced any number of dramatic challenges over the last few years.
      Recently, People across the nation focused their attention to the West coast of
      Florida, and towards the hospice where Terri Schiavo resided during the remaining
      days of her life. All of us involved in home care and hospice are keenly aware of
      the great dilemmas that can arise when considering the cessation of life
      sustaining technologies, hydration, or nutrition. We may have faced those
      dilemmas both personally as well as professionally. For Terri Schiavo, like
      numerous others in like circumstances, decisions most often made in private,
      became a very public matter subject to the attention of the mass media,
      pollsters, and politicians.

PMID- 15966155
TI  - Telehome care--legal advice for telehealth pioneers.
AB  - The expansion of technology into the health care field brings exciting potential
      for better service and quality care for an ever growing market. This is
      particularly an exciting time and a superb opportunity for providers serving
      patients in rural areas. Proper education and advice of counsel regarding the
      legal ramifications of establishing a telehealth program in your business is
      vital, as Mr. Waters points out in this article, and provider the reader key
      caveats to consider.

PMID- 15966156
TI  - Medicare introduces new appeals process.
AB  - This article addresses the wholly reformed appeals process in a broad based
      manner. It describes only the basic structure of a new appeals system. Appealing
      parties should be careful to learn in more detail the new system prior to
      pursuing an appeal. While many appeals can be pursued without legal counsel, it
      may be advisable to initially utilize an attorney for appeals until one becomes
      familiar and comfortable with the new process. Despite any of the shortcomings
      discussed above or new obstacles created by CMS in the rules, the appeals process
      should continue to be a very useful mechanism to successfully reverse
      inappropriate claim denials.

PMID- 15966157
TI  - New hospice pre-election evaluation and counseling service may only be given by
      hospice employee.

PMID- 15966158
TI  - Make ideas visible and stimulate creativity with '"Storyboarding".

PMID- 15966159
TI  - Conmunication is key.

PMID- 15966160
TI  - Emerging trends in home care sales and marketing.

PMID- 15966161
TI  - Bluegrass blessing.

PMID- 15966162
TI  - Action on long-term care... at last.

PMID- 15966163
TI  - [What can be done for problematic asthma patients?].

PMID- 15966164
TI  - [Nose mask against cardiac death and risk of accident].

PMID- 15966165
TI  - [Healing needles soon to be covered by federal insurance?].

PMID- 15966166
TI  - [Chronic borreliosis? No, psychosomatic illness! (interview by Dr. med. Brigitte
      Moreano)].

PMID- 15966167
TI  - [Eye diseases in older patients].

PMID- 15966168
TI  - [Surgical treatment of cataract].
AB  - Today, the most frequently performed of all operative interventions is considered
      to be surgery for cataract. Modern surgical techniques applied under local
      anesthesia, tiny incisions that close spontaneously, reliable biometric methods,
      and the availability of artificial lenses, all combine to produce excellent
      results. In view of the low complication rate, this procedure can be recommended
      even in very old patients.

PMID- 15966169
TI  - [Circulatory disorders of the retina].
AB  - Cardiovascular diseases lead to systemic vascular regression, which, among other
      consequences, may result in an impairment of retinal perfusion. In view of the
      high level of comorbidity observed in patients with circulatory problems
      affecting the retina, the early recognition of mild forms of vascular retinopathy
      is of considerable importance. A major prerequisite for an improvement in outcome
      is the recognition of the fact that most circulatory disorders of the retina are
      due to systemic vascular disease, and the eye is an important prognostic
      indicator of cardiovascular morbidity and mortality. As a result, effective
      communication between family physician/internist and ophthalmologist is basic to
      the successful treatment of these diseases of the eye.

PMID- 15966170
TI  - [Age-related macular degeneration].
AB  - In the western world, macular degeneration is the most common cause of severe
      loss of vision and blindness in persons older than 50. The underlying cause of
      the condition is a disturbance in the interaction between the retina and choroid
      of the macula. Apart from age itself, genetic disposition and smoking are
      confirmed risk factors. In the initial stages, the patient experiences merely a
      mild blurring of vision. The wet form, which is usually progressive, is
      experienced as an acute loss of vision or distortion of the objects viewed.
      Underlying this wet macular degeneration is of new vessel growth from the
      choroid, known as choroidal neovascularization, which as a result of exudation of
      fluid and bleeding into the macula, destroys central vision. Apart from the
      administration of vitamins to slow down progression, laser coagulation,
      photodynamic treatment or vitreoretinal surgery may be helpful in some cases. A
      specific causal therapy is, however, not available.

PMID- 15966171
TI  - [Recommendations for the management of diabetic patients with nephropathy].
AB  - In industrialized countries diabetic nephropathy is now the most common cause of
      end-stage renal disease and is associated not only with a high morbidity rate,
      but also a dramatic increase in mortality. The 5-year survival rate of diabetic
      patients on hemodialysis is 25-30% and is thus comparable with that of patients
      with colorectal cancer. The increasing numbers of diabetics on renal replacement
      therapy also put a great financial strain--on average 40,000-50,000 euros per
      patient and year--on our health care system. An increased rate of micro- and
      macrovascular complications is found already in early stages of diabetic
      nephropathy. Despite the existence of suitable screening methods and effective
      interventional strategies for these high-risk patients, their practical
      implementation leaves much to be desired. In particular there is much room for
      improvement in the cooperation between general practitioners, diabetologists and
      nephrologists.

PMID- 15966172
TI  - [Good blood pressure control even in overweight patients].

PMID- 15966173
TI  - [Assistant is supposed to replace general practitioner].

PMID- 15966174
TI  - [Spontaneous blood blisters].

PMID- 15966175
TI  - Hepatocellular carcinoma and interferon therapy in HCV compensated cirrhosis:
      evaluation in relation to virological response.

PMID- 15966176
TI  - Does the psychological request of the patient justify the surgery for hepatic
      hemangioma?
AB  - BACKGROUND/AIMS: The incidental finding of hemangiomas has increased, but the
      problem of the correct surgical indications of this tumor has yet to be solved.
      The aim of this work is to establish whether the psychological request of surgery
      from patients known to have a benign tumor of the liver must be avoided or not.
      METHODOLOGY: Age, sex, symptoms, estroprogestinic oral therapy, methods of
      diagnosis, surgical procedures, morbidity, mortality, postoperative hospital stay
      and follow-up of the patients affected by hepatic hemangioma, observed from 1992
      to 2002 in our institution, have been considered. RESULTS: Seventeen patients,
      with a mean age of 44 years (range 26-72), were hospitalized for hepatic
      hemangioma, 8 (47%) of them were operated on and 9 (53%) were managed by
      observation. The operated patients presented various symptoms. One patient was
      operated on for traumatic rupture of the hemangioma. Non-operated patients were
      asymptomatic or with slight dyspeptic symptoms not related with the tumor. The
      first diagnostic radiological examination was ultrasonography (US) in all cases.
      All lesions were larger than 4cm. The types of surgical procedures were 5
      enucleations, and 3 hepatic resections. All operated patients resolved their
      clinical symptomatology, except two patients that had requested surgery for
      psychological implications. These patients presented their symptoms again after
      2and 3 years of follow-up respectively. CONCLUSIONS: Our results suggest that
      liver hemangiomas should be operated for symptoms well related to the tumor or
      for bleeding. Psychological requests from the patients should be avoided every
      time.

PMID- 15966177
TI  - Experience with mesocaval shunt with autologous jugular vein interposition in
      patients with Budd-Chiari syndrome.
AB  - BACKGROUND/AIMS: In the present era of interventional radiology and liver
      transplantation, the role of mesocaval shunt surgery for portal hypertension in
      Budd-Chiari syndrome is reviewed. METHODOLOGY: This study analyzed the management
      of 35 patients with Budd-Chiari syndrome between June 1994 and June 2004 in our
      institution. During this 10-year interval, 31 of the 35 patients with Budd-Chiari
      syndrome underwent shunt procedures and four patients underwent liver
      transplantation. Mesocaval shunts were preferred in 27 patients and seven of
      these patients required prior caval stenting. One portocaval shunt was performed
      in a patient having a thrombosed mesocaval shunt. In all mesoaval shunt
      procedures the patient's internal jugular vein was used as an interposition graft
      between the superior mesenteric vein and inferior vena cava. In four patients
      with thrombosed vena cava a mesoatrial shunt was performed using
      polytetrafluoroethylene graft while four patients with established cirrhosis
      underwent orthotopic liver transplantation. RESULTS: In the group of mesocaval
      shunts, 3 patients were lost in the early postoperative period with a mortality
      rate of 11%, 2 of them due to thrombosed shunts and one of them due to pneumonia.
      The median follow-up was 42 months (6-120 months) and one patient experienced
      shunt thrombosis and died afterwards due to the complications of portal
      hypertension. In the whole series the patency rate of the mesocaval shunt was
      89%. CONCLUSIONS: Patients with Budd-Chiari syndrome can be managed by a
      combination o f shuntsurgery, interventional radiology and liver transplantation.
      Our results demonstrate the effectiveness of mesocaval shunt procedure with
      autologous jugular vein interposition to maintain long-term patency and survival.

PMID- 15966178
TI  - Evaluating the combination of molecular prognostic factors in tumor
      radiosensitivity in rectal cancer.
AB  - BACKGROUND/AIMS: The local recurrence ratio following surgery alone is higher in
      patients with rectal cancer than in those with colon cancer. Preoperative
      radiotherapy reduces the rate of local recurrence and improves the chances of
      survival in patients with resectable advanced rectal carcinoma. Identification of
      predictive indicators of radiosensitivity is useful in selecting patients best
      suited for preoperative radiotherapy and thus helps to avoid unnecessary
      preoperative treatment. We investigated whether the combination of Ku, p53, p21,
      and p16 predicted tumor radiosensitivity. METHODOLOGY: We studied 96 cases with
      advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, all
      immunoreactive nuclei of cells stained positive for Ku, p53, p21, and p16 were
      evaluated by immunohistochemistry. The expression of p53, p21 and p16 in more
      than 5% of tumor cells were defined as positive, whereas both Ku70 and Ku86
      protein in more than 70% of such cells were defined as Ku positive. The
      expression patterns of Ku, p53, p21, and p16 were examined for association with
      tumor radiosensitivity, which was determined according to the criteria of
      histopathologic assessment of radiotherapy effects. RESULTS: Univariate analysis
      showed a correlation between the expression patterns of Ku, p53, p21, and p16 and
      tumor radiosensitivity, while multivariate analysis showed that the expression
      pattern of Ku and p16 significantly correlated with tumor radiosensitivity. The
      combination of Ku and p16, or Ku, p53, p21 and p16 was therefore a good
      predictive marker for tumor radiosensitivity. CONCLUSIONS: These findings tend to
      support the hypothesis that the combination of Ku, p53, p21, and p16 expression
      after radiotherapy can act as a marker for radiosensitivity. Further
      investigation is needed, as the number of cases in this study was limited.

PMID- 15966179
TI  - Collagen IV is a predictor for clinical course in patients with malignant
      obstructive jaundice.
AB  - BACKGROUND/AIMS: Increases in the serum extracellular matrix proteins (ECMPs)
      have been described in studies on cholestasis, therefore we investigated the
      serum levels of collagen IV, aminoterminal propeptide of type III procollagen,
      and hyaluronic acid prior to percutaneous transhepatic biliary drainage (PTBD) to
      evaluate its potential as a predictor for prolonged bilirubin clearance and
      clinical course in patients with malignant obstructive jaundice (MOJ).
      METHODOLOGY: Serum levels of ECMPs were prospectively investigated in 42 patients
      with MOJ prior to PTBD. The study group was subdivided according to the bilirubin
      clearance, and was also subdivided according to the determined level of collagen
      IV (cut-off point of 260 ng/mL). RESULTS: Serum collagen IV was identified as an
      independent risk factor for prolonged bilirubin clearance (P=0.006). Receiver
      operating-characteristic curve analysis revealed that serum collagen IV had a
      diagnostic accuracy of 79% at the cut-off point of 260 ng/mL. Furthermore, these
      results indicated that the level of collagen IV is a reliable marker of
      postoperative liver failure (P=0.029) and predictor of death from liver failure
      (P=0.02). CONCLUSIONS: Elevated serum collagen IV is a feature of MOJ commonly
      associated with prolonged bilirubin clearance, and a useful indicator of clinical
      course, postoperative morbidity, and mortality in patients with MOJ.

PMID- 15966180
TI  - Endoscopic total layer resection with laparoscopic sentinel node dissection and
      defect closure for duodenal carcinoid.
AB  - Tiny duodenal carcinoid is easily treated by endoscopic mucosal resection method.
      On the other hand, this tumor develops in the deeper layer of the mucosa,
      therefore it invades like a submucosal tumor. The resection of the total layer is
      sometimes needed to get a tumor-free margin. Moreover, lymph node metastasis is
      not predicted only by tumor size. Laparoscopic surgery is less invasive compared
      with conventional open surgery. We describe a new method, endoscopic total layer
      resection with laparoscopic sentinel node dissection and defect closure. This
      type of combined method should be performed in order to help decide whether to
      convert to conventional lymph node dissection, or not.

PMID- 15966181
TI  - Percutaneous transhepatic insertion of metal stents with a double-pigtail
      catheter in afferent loop obstruction following distal gastrectomy.
AB  - We report successful outcome following transhepatic insertion of metal stents
      with a double-pigtail catheter in a patient with afferent loop syndrome caused by
      recurrent gastric carcinoma. A 77-year-old man was admitted with a 2-week history
      of fever, right upper quadrant pain, and jaundice. His past medical history
      included distal gastrectomy for treatment of gastric cancer two years previously.
      Abdominal computed tomography revealed marked dilation of the jejunal limb and
      intrahepatic bile duct. We diagnosed the patient with afferent loop syndrome
      resulting from recurrent cancer. Percutaneous transhepatic biliary drainage was
      performed, and a catheter was placed beyond the papilla of Vater. Approximately
      1300 mL of turbid jejunal contents were removed. Symptoms resolved by one day
      after initiation of drainage. After 1 week, a sheath introducer was inserted
      beyond the point of stenosis, and two metal stents were placed. A double-pigtail
      catheter was inserted into the metal stents to prevent migration. Good stent
      placement was confirmed and the drainage catheter was removed.

PMID- 15966182
TI  - Experiences with single-layer biliodigestive anastomosis.
AB  - BACKGROUND/AIMS: The right technique for biliodigestive anastomosis is still
      being researched. The present study investigated the single-layer method.
      METHODOLOGY: The authors performed single-layer biliodigestive anastomosis in 153
      patients between 1995 January and 2000 August. Among the operative procedures
      there were pancreatoduodenectomy, pancreatic head resection, pancreatic drainage
      operation, GEA and in a small percentage of the cases other procedures. 88.2% of
      the anastomoses were done with a continuous suture technique, mainly with 4/0
      PDS. RESULTS: In 96 cases the diagnosis was tumor, while the others were benign
      diseases. Hepatico- or choledochojejunostomy was twice as much as
      cholecystojejunostomy. There were complications in 29.4% of the cases, from which
      the rate of biliary fistula was 3.9%. All fistulas healed for conservative
      therapy. Reoperation was in 7.1%, the operative mortality was 9.8%.
      Preoperatively 77.1% of the patients had cholestasis, which improved in all cases
      postoperatively. CONCLUSIONS: In summary the authors offer the single-layer
      technique for biliodigestive anastomosis.

PMID- 15966183
TI  - Isolated bacteria and susceptibilities to antimicrobial agents in biliary
      infections.
AB  - BACKGROUND/AIMS: A total of 209 bacterial strains were isolated from patients
      with biliary infection in our department between January 1982 and December 2000.
      METHODOLOGY: Antimicrobial susceptibility tests were conducted to ascertain the
      presence of drug-resistant bacteria. RESULTS: The breakdown of the 109 strains
      from the patients with primary biliary infections was as follows: 70 strains of
      gram-negative aerobic bacteria; 27 strains of gram-positive aerobic bacteria; 6
      strains of gram-negative anaerobic bacteria; and 6 strains of gram-positive
      anaerobic bacteria. Among the 100 strains isolated from the patients with
      postoperative infection, the frequency of anaerobic bacteria was similar, but the
      frequency of gram-negative aerobic bacteria was lower at 55 strains, whereas
      frequency of gram-positive aerobic bacteria was higher at 36 strains. Of the 70
      strains of gram-negative aerobic bacteria isolated from patients with primary
      biliary infection, the following four bacteria accounted for 75% of the total:
      Klebsiella pneumoniae, Escherichia coli, Enterobacter spp., and Pseudomonas
      aeruginosa. CONCLUSIONS: The frequencies of gram-negative aerobic bacteria were
      high among patients with primary biliary infection, while those of gram-positive
      aerobic bacteria were high among patients with postoperative biliary infection.
      Although VRE was not isolated, the frequency of MRSA was extremely high.

PMID- 15966184
TI  - Clinicopathological analysis of cystic duct carcinoma.
AB  - BACKGROUND/AIMS: Gallbladder carcinoma is the most common malignancy of the
      biliary tract, while the clinical features of cystic duct carcinoma remain
      unexplored. METHODOLOGY: Clinicopathological data of 8 cases of cystic duct
      carcinoma were retrospectively analyzed. RESULTS: The sample included 5 men and 3
      women, with a mean age of 66+/-10 years (range, 49-79 years). Clinical
      manifestations included jaundice (n=6) and/or abdominal pain (n=6). Two of the
      patients presented as acute cholecystitis. Preoperative work-ups included
      ultrasonography (n=8), computed tomography (n=7), and endoscopic retrograde
      cholangiography (n=6)/or magnetic resonance cholangiography (n=2). Meanwhile, the
      preoperative diagnoses included cystic duct neoplasms (n=3), common hepatic duct
      neoplasms (n=4), and gallstones with acute cholecystitis (n=1). Radical
      procedures, including cholecystectomy, resection of extrahepatic bile duct, and
      lymph node dissection, were performed in six patients, while palliative
      cholecystectomy was performed in the remaining two. Notably, five of eight cases
      displayed lymph node metastasis along the hepaticoduodenal ligament. Median
      survival was 15 months (range, 6 to 26 months). Two cases with no lymph node
      metastasis were alive and disease free at 23 months and 26 months, respectively.
      CONCLUSIONS: Cystic duct carcinoma is rare. Neoplasm of the cystic duct should be
      suspected in patients presenting with cystic duct obstruction accompanied by
      distended nonfunctioning gallbladder without evidence of stone impaction in the
      cystic duct. The prognosis of cystic duct carcinoma remains dismal. However, for
      those patients in whom tumors are detected in early stage, curative radical
      resections possibly provide the chance of potential curable.

PMID- 15966185
TI  - The use of stents for duct-to-duct anastomoses of biliary reconstruction in
      orthotopic liver transplantation.
AB  - BACKGROUND/AIMS: Biliary anastomotic complications remain a major cause of
      morbidity in liver transplant recipients. The objective of this retrospective
      study is to reassess the use of anastomotic stents for biliary reconstruction
      while focusing on an end-to-end choledochocholedochostomy (EECC) in orthotopic
      liver transplantation (OLT). METHODOLOGY: EECC for the biliary reconstruction in
      OLT was performed in 115 patients. Sixty-three had their bile duct reconstructed
      over a T-tube stent (S group) while the remaining 52 patients underwent the same
      procedure without the stent (non-S group). The two groups were compared in terms
      of biliary complications and the conversion rate to a hepaticojejunostomy (HJS).
      RESULTS: Twenty-three biliary complications were observed in the OLT patients. In
      the S group, the incidence of a biliary leak was 12.7%, 8 of 63 patients in which
      5 patients showed a bile leak when T tubes were removed. The rate of biliary
      stricture in the S group was 25.4%, or 16 patients. This stricture rate was not
      significantly different from the 13.5% rate observed in the non-S group
      (p=0.086). In the non-S group, 7 patients showed a biliary stricture. Four of 7
      patients also developed a bile leak identified to be an anastomotic leak, which
      consequently resulted in HJS. A total of 6 patients, 5.2% of all OLT patients,
      underwent a subsequent revision of their primary anastomoses. The incidence of
      conversion from EECC to HJS in the non-S group, 57.1% was significantly higher
      than that in the S group, 12.5% (p=0.046). CONCLUSIONS: EECC (i.e. with or
      without a T-tube stent) is both a safe and effective technique for biliary
      reconstruction in OLT. However, the conversion rate from EECC to HJS in the non-S
      group was significantly higher than that in the S group. An indwelling T-tube
      stent is therefore considered to be useful for both achieving the lowest possible
      rate of severe anastomotic stricture and to prevent any subsequent intervention.

PMID- 15966186
TI  - Endoscopic sphincterotomy and papillary balloon dilation for bile duct stones.
AB  - BACKGROUND/AIMS: There are many reports of the results of endoscopic
      sphincterotomy (EST) for common bile duct stones. Recently, there were several
      reports on the results of endoscopic papillary balloon dilation (EPBD) for this
      condition. However, there have been few reports about a comparison between EST
      and EPBD. METHODOLOGY: Between Oct. 1994 and Dec. 1998, 196 consecutive patients
      underwent 102 EST or 94 EPBD. RESULTS: EST and EPBD were successful in 100 of 102
      (98.0%), and all 94 patients. Bile duct clearance was achieved in 88 (88.0%) in
      the EST group and 88 (95.7%) in the EPBD group. Early complications occurred in
      13 (13.0%: 3 acute pancreatitis, 4 cholangitis, 2 cholecystitis, 2 bleeding, 2
      perforation) in the EST group and 16 (17.0%: 7 acute pancreatitis, 4 cholangitis,
      4 cholecystitis, 1 basket impaction) in the EPBD group. Three patients (1
      bleeding, 2 perforations) underwent emergent surgery after EST. CONCLUSIONS: The
      rate of bile duct clearance with EPBD was comparable to that with EST. Early
      complications did not differ between EST and EPBD. The use of EST tended to be
      associated with a lower incidence of acute pancreatitis, a higher incidence of
      bleeding, and a higher rate of perforation.

PMID- 15966187
TI  - Magnetic resonance cholangiopancreatography in cholestatic diseases.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of magnetic resonance
      cholangiopancreatography in cholestasis. METHODOLOGY: Sixty-seven patients with
      cholestasis underwent ultrasound and magnetic resonance cholangiopancreatography,
      subsequently. The results of ultrasound and magnetic resonance
      cholangiopancreatography were interpreted by two independent radiologists.
      RESULTS: According to ultrasonographic findings intra- and extrahepatic
      cholestasis were diagnosed in 62.7% and 37.3% of patients, respectively. Magnetic
      resonance cholangiopancreatography revealed intra- and extrahepatic cholestasis
      in 52.2% and 47.8% of patients at the same group, respectively (p=0.016,
      kappa=0.789). Endoscopic retrograde cholangiopancreatography was indicated in
      37.3% of patients (22.4% diagnostic, 14.9% therapeutic) according to
      ultrasonographic findings. However, 41.8% of patients had indication for
      endoscopic retrograde cholangiopancreatography following magnetic resonance
      cholangiopancreatography in the same group. In 20% of patients who needed
      diagnostic endoscopic retrograde cholangiopancreatography according to
      ultrasonographic findings, endoscopic retrograde cholangiopancreatography wasn't
      indicated after magnetic resonance cholangiopancreatography. Similarly, 8.9% of
      patients who didn't have indication for endoscopic retrograde
      cholangiopancreatography according to ultrasonographic findings underwent
      endoscopic retrograde cholangiopancreatography (p=0.508, kappa=0.72).
      CONCLUSIONS: Magnetic resonance cholangiopancreatography is valuable in diagnosis
      of extrahepatic cholestasis in patients suspected with intrahepatic cholestasis
      according to ultrasonographic findings. Magnetic resonance
      cholangiopancreatography does not prevent endoscopic retrograde
      cholangiopancreatography requirement significantly in patients who need
      diagnostic endoscopic retrograde cholangiopancreatography following
      ultrasonography.

PMID- 15966188
TI  - Hyperamylasemia induced by percutaneous papillary balloon dilatation for
      symptomatic choledocholithiasis.
AB  - BACKGROUND/AIMS: We investigated the relationship between percutaneous papillary
      balloon dilatation (PPBD) and hyperamylasemia after PPBD. METHODOLOGY: We studied
      the rate of pancreatitis and asymptomatic hyperamylasemia after PPBD for
      choledocholithiasis in 64 symptomatic patients. Pancreatitis was defined as
      epigastric pain combined with at least a 3-fold rise in serum amylase at 24 hours
      after PPBD. Asymptomatic hyperamylasemia was defined as a rise in serum amylase
      (normal range, 50 to 160 IU/L) without epigastric pain. RESULTS: The stones were
      successfully pushed out into the duodenum in all patients. Three patients
      developed post-PPBD pancreatitis, graded moderate in one and mild in two. Serum
      amylase values were elevated over the normal upper limit in 21 patients, 33%,
      over 3-fold in 10, 16% over 1000 IU/L in 6, 9%. Asymptomatic hyperamylasemia was
      observed in 18 patients. The amylase value after PPBD was elevated to more than
      160 IU/L in 44% (17/39) of patients 80 years old or under vs. 16% (4/25) of
      patients older than 80 and in 23% (10/44) of patients with intrahepatic bile duct
      dilatation on admission vs. 55% (11/20) of patients without it, with a
      significant difference, respectively (p<0.05). The amylase value after PPBD was
      elevated to more than 1000 IU/L in 15% (6/39) of patients 80 years old or under
      vs. 0% (0/25) of patients older than 80 and in 29% (4/14) of patients with bile
      duct stones having a horizontal diameter of 8mm or smaller and 4% (2/50) of
      patients with stones larger than 8mm (p < 0.05 and p<0.01, respectively).
      CONCLUSIONS: We believe that postoperative continuous decompression of the bile
      duct by PPBD is reliable and that it contributed to the prevention of severe
      pancreatitis. We conclude that PPBD can be performed more safely in symptomatic
      patients older than 80 with choledocholithiasis with intrahepatic bile duct
      dilatation at the time of admission.

PMID- 15966189
TI  - Ki-ras mutations in codon 12 and p53 mutations (biomarkers) and cytology in bile
      in patients with hepatobiliary-pancreatic carcinoma.
AB  - BACKGROUND/AIMS: The differentiation between benign and malignant jaundice is
      sometimes difficult even with modern diagnostic modalities. With recent advances
      in molecular biology, Ki-ras point mutation in codon 12 and p53 mutation have
      been reported as novel biomarkers of hepatobiliary and pancreatic carcinoma. The
      purpose of this study was to compare exfoliative bile cytology and biomarkers of
      the bile in patients with hepatobiliary and pancreatic diseases. METHODOLOGY:
      Cytologic examination and novel biomarkers, point mutations of codon 12 of Ki-ras
      and p53 mutations, were examined in the biliary tract bile aspirated through
      percutaneous transhepatic biliary drainage (PTBD) tube in 30 Japanese patients
      with benign and malignant hepatobiliary and pancreatic diseases. RESULTS:
      Sensitivity of the exfoliative bile cytology for malignant conditions was 31% and
      specificity 100%, while sensitivity of molecular markers of the bile was 25% and
      specificity 93%. When the cytologic examination and genetic study were in
      conjunction, sensitivity increased to 50% and specificity remained 93%.
      CONCLUSIONS: These findings suggest that genetic examinations of the bile, when
      used in conjunction with cytology, may improve the diagnostic yield for suspected
      malignant tumors of the hepatobiliary and pancreatic system.

PMID- 15966190
TI  - Right hepatic duct opening into the cystic duct: the role of pre- and
      intraoperative cholangiography.
AB  - Although an aberrant hepatic duct entering the cystic duct is not especially
      rare, the main right hepatic duct entering the cystic duct is extremely rare. A
      69-year-old woman developed severe intermittent right upper quadrant pain and
      high fever. A diagnosis of acute calculus cholecystitis was made by radiographic
      examinations. Magnetic resonance cholangiopancreatography demonstrated dilatation
      of the right hepatic duct, but could not identify the junction of the right
      hepatic duct and the cystic duct. Endoscopic retrograde cholangiopancreatography
      established that the right hepatic duct joined the cystic duct and that
      cholecystolithiasis was present. As the right hepatic duct entering the cystic
      duct can lead to ductal injury, this anomaly should be kept in mind when
      performing laparoscopic cholecystectomy. Pre- and intraoperative cholangiography
      contribute to the avoidance of iatrogenic bile duct injury. When the right
      hepatic duct drains into the cystic duct, the gallbladder should be removed
      distal to the junction of the hepatic and cystic ducts.

PMID- 15966191
TI  - Long-term survival after extended surgical resection of intrahepatic
      cholangiocarcinoma with extensive lymph node metastasis.
AB  - We present a case of long-term survival in a patient that involved intrahepatic
      cholangiocarcinoma that metastasized to the paraaortic lymph nodes. A 62-year-old
      man underwent extended left hepatic lobectomy with caudate lobe resection,
      extrahepatic bile duct resection, portal vein resection and reconstruction, and
      middle hepatic vein resection and reconstruction with lymph node dissection for a
      liver tumor that was located in the caudate lobe. Histological examination of the
      resected specimen revealed moderately differentiated adenocarcinoma compatible
      with cholangiocarcinoma, and lymph node metastases were found in the area of the
      hepatoduodenal ligament and the paraaortic region. After surgical resection,
      recurrence was detected twice in the lymph nodes at the site of the left
      supraclavicular region. These recurrent tumors were completely eliminated by
      systemic chemotherapy with cisplatin or mitomycin C. The patient is now doing
      well 6 years and 5 months after surgical treatment. In this case, there was only
      one tumor, and the preoperative serum carbohydrate antigen 19-9 level was normal.
      In addition, heterozygosity was retained at the loci on chromosome 8p. These
      findings suggested that tumor in the present case was less aggressive, despite
      the nodal spread. The extensive surgical approach may have contributed to the
      long-term survival of this patient, while the recurrent tumor was sensitive to
      antitumoral agents.

PMID- 15966192
TI  - Unresectable hilar cholangiocarcinoma completely reduced by external radiation
      therapy.
AB  - A 68-year-old woman was referred to our hospital with liver dysfunction.
      Abdominal ultrasonography showed an isoechoic mass in the hepatic hilum.
      Abdominal computed tomography (CT) disclosed a homogenous mass adjacent to the
      portal bifurcation, and endoscopic retrograde choledocho-pancreatography (ERCP)
      revealed complete obstruction from the common hepatic duct to the hepatic duct
      confluence. After insertion of the endoscopic nasobiliary drainage (ENBD) tube,
      laparotomy was performed, revealing an approximately 5x6-cm elastic hard mass at
      the hepatic hilum, mainly spreading to the left hepatic duct, and involving
      surrounding vascular structures such as the portal vein and right and left
      hepatic arteries. Therefore, she was treated by external radiation therapy (ERT)
      of 60 Gy in 30 sessions after insertion of endoscopic retrograde biliary drainage
      (ERBD) tubes to bilateral hepatic ducts to replace the ENBD tube. After the
      completion of ERT, she was discharged from the hospital in good health. Three
      months later, she was readmitted for cholangitis and received antibiotic
      treatment. Surprisingly, abdominal CT disclosed complete remission of the tumor.
      ERCP revealed patency of the common hepatic duct and hepatic duct confluence.
      Therefore, the ERBD tubes were removed. Specimens from the hepatic duct
      confluence, and bilateral hepatic ducts showed no malignancy histologically. She
      is doing well without recurrence more than 4 years after surgery.

PMID- 15966193
TI  - Anatomical basis of the liver hanging maneuver.
AB  - BACKGROUND/AIMS: The anterior approach to right hepatectomy using the liver
      hanging maneuver without liver mobilization claims to be anatomically evaluated.
      During this procedure a 4 to 6-cm blind dissection between the inferior vena cava
      and the liver is performed. Short subhepatic veins, entering the inferior vena
      cava could be torn and a hemorrhage, difficult to control, could occur.
      METHODOLOGY: On 100 corrosive casts of livers the anterior surface of the
      inferior vena cava was studied to evaluate the position, diameter and draining
      area of short subhepatic veins and inferior right hepatic vein. The width of the
      narrowest point on the planned route of blind dissection was determined. RESULTS:
      The average value of the narrowest point on the planned route of blind dissection
      was 8.7+/-2.3mm (range 2-15mm). The ideal angle of dissection being 0 degrees was
      found in 93% of cases. In 7% we found the angle of 5 degrees toward the right
      border of inferior vena cava to be the better choice. CONCLUSIONS: Our results
      show that liver hanging maneuver is a safe procedure. With the dissection in the
      proposed route the risk of disrupting short subhepatic veins is low (7%).

PMID- 15966194
TI  - Current diagnosis and treatment of gastrointestinal carcinoids in a series of 101
      patients: the significance of serum chromogranin-A, somatostatin receptor
      scintigraphy and somatostatin analogues.
AB  - BACKGROUND/AIMS: Carcinoids are relatively rare tumors that arise from
      neuroendocrine cells and have proved to be slow growing malignancies which
      involve many organs and most frequently the gastrointestinal (GI) tract. Herein
      we present in this study 101 pts with carcinoid tumors that originated from the
      GI tract and pancreas. Also, we analyze the clinical and pathological features,
      pointing out the characteristics of this group of neoplasms and describing our
      diagnostic and therapeutical approach, in parallel with a brief review of the
      literature. METHODOLOGY: One hundred and one (66 females and 35 males, aged from
      16 to 79 years) pts were included in our study. The primary tumors originated
      from the GI tract in 97/101 pts (appendix 34%, small intestine 31%, stomach 14%,
      duodenum 6%, colon 6%, rectum 3%) and from the pancreas in 4/101 (4%). The
      diagnosis was confirmed histologically in all cases, after surgical excision of
      the primary tumor or by biopsies taken during endoscopy. All pts were evaluated
      several times per year with clinical, biochemical and imaging assessments,
      including neuroendocrine markers [urinary 5-Hydroxyindoleacetic acid (5-HIAA),
      serum Chromogranin-A (CgA)] and Somatostatin Receptor Scintigraphy (OCTREOSCAN).
      The follow-up period ranged between 1.5 to 12.5 years (mean time: 5 years and 3
      months) and it is still in progress. RESULTS: Patients were referred to us with
      gastrointestinal symptoms or symptoms of the "carcinoid syndrome" (flushing, and
      diarrhea), depending mainly on the location of the primary tumors and the
      existence or not of metastases. CgA and 5-HIAA levels were increased especially
      in metastatic tumors. Localization of the primary tumors to facilitate surgery
      was made by many imaging techniques (US, CT, MRI, Enteroclysis, OCTREOSCAN) and
      endoscopic procedures. OCTREOSCAN was positive in 94% pts with metastatic
      disease. Furthermore, it revealed the primary and the metastatic lesions in 16%
      and 33% of pts with carcinoids of the small intestine respectively, while other
      conventional imaging procedures (including MRI) were negative at the same time.
      Seventy-four percent of the pts underwent a surgical resection of the primary
      tumor, while in 21%, an endoscopic polypectomy was performed. All pts with
      metastatic tumors and positive OCTREOSCAN, were treated with Somatostatin
      analogues, which resulted in control of symptoms (75%), stabilization of tumor
      growth (71%) or tumor shrinkage (9%). A combined therapy with the addition of
      interferon-a was initiated in pts in whom, despite the increase of drug dosage
      and the shortening of administration intervals, a complete clinical and
      biochemical response was no more achieved with Somatostatin analogues alone.
      Pancreatic carcinoids and also those that originated from the proximal colon were
      found to have worst prognosis. CONCLUSIONS: a) Tumor size (especially in
      appendiceal and gastric carcinoids) and, also, the dispersion of disease, highly
      predict the evolution of the patients; b) serum Chromogranin-A seems to be a very
      useful tumor marker for the diagnosis and follow-up of pts with GI carcinoids; c)
      the introduction of new imaging techniques and especially OCTREOSCAN contributes
      to a better localization of the primary tumors and their metastases, as well as,
      to the right decision of the appropriate medical treatment; d) surgical excision
      is the treatment of choice in nonmetastatic tumors; and e) in pts with metastatic
      disease, the administration of Somatostatin analogues improves their quality of
      life.

PMID- 15966195
TI  - Hepato-pancreaticoduodenectomy with preservation of the collateral arterial
      arcade in the head of the pancreas in a patient with celiac axis stenosis.
AB  - Hepato-pancreaticoduodenectomy was performed for common bile duct carcinoma
      associated with celiac axis stenosis. To secure arterial blood flow to the upper
      abdominal organs, we preserved the anterior arcade in the pancreas head acting as
      a collateral pathway between the superior mesenteric artery and the celiac
      artery. This is another valid alternative procedure for pancreaticoduodenectomy
      in a patient with celiac axis stenosis.

PMID- 15966196
TI  - Sequential progression and intraductal spread of invasive ductal adenocarcinoma
      of the pancreas arising from around the main pancreatic duct.
AB  - A 76-year-old woman was admitted to our hospital after increased transaminase,
      hepato-biliary enzyme levels, and tumor markers were found. Abdominal contrast
      computed tomography revealed a mass (20 x 18 mm) in the uncus of the pancreas.
      Magnetic resonance cholangiopancreatography showed an abrupt narrowing with the
      dilatation of the peripheral main pancreatic duct (MPD) in the pancreatic head.
      Endoscopic retrograde cholangiopancreatography showed only dilatation of the
      lower bile duct; insertion of the cannula was not seen because the MPD was
      obstructed. The patient underwent a Whipple-pancreatoduodenectomy.
      Histopathological and immunohistochemical examinations led to a diagnosis of
      sequential progression and intraductal spread of invasive ductal adenocarcinoma
      of the pancreas arising from around the main pancreaticduct. Interestingly, the
      intraductal spread was approximately 20 mm to the point where the carcinoma began
      to infiltrate. To the best of our knowledge, there have been no other reported
      cases of such broad intraductal spread, indicating that noninvasive lesions that
      replace the normal epithelia can be broader than those reported previously.

PMID- 15966197
TI  - Transhepatic portal venous angioplasty with stenting for bleeding jejunal
      varices.
AB  - A 54-year-old woman, who had undergone pancreatoduodenectomy with resection of
      the portal vein and intraoperative radiation therapy for cancer of the lower bile
      duct 16 months before, visited our institution complaining of melena. To identify
      the cause of bleeding and severe anemia, we performed gastrointestinal endoscopy
      but could detect no obvious source. The portal phase of the superior mesenteric
      arteriography and percutaneous transhepatic portography revealed severe stenosis
      of the extrahepatic portal vein, which corresponded to the end-to-end anastomosis
      of the portal vein, and hepatofugal collaterals. Extravasations into the afferent
      loop of the jejunum were detected only with portography. These findings suggested
      that portal hypertension due to extrahepatic portal obstruction led to bleeding
      varices. Subsequent to percutaneous transhepatic portography, we dilated the
      stenosis of the extrahepatic portal vein using a balloon catheter and placed an
      expandable metallic stent there. Portography after the treatment revealed the
      disappearance of the hepatofugal flow to collaterals and extravasations, and the
      patient has had no further episodes of gastrointestinal bleeding since. In
      conclusion, for patients with bleeding varices due to extrahepatic portal
      obstruction, especially after abdominal surgery, percutaneous transhepatic
      angioplasty is considered to be the treatment of choice because of its efficiency
      and minimal invasiveness.

PMID- 15966198
TI  - Long-term response of primary biliary cirrhosis (stage I) to therapy with
      ursodeoxycholic acid.
AB  - We report about a 56-year-old asymptomatic female patient, who was examined in
      April 1991 for an increase of biochemical parameters of the liver. Based on the
      biochemical and serological results (abnormal cholestatic liver function tests,
      positive antimitochondrial antibodies) as well as liver biopsy primary biliary
      cirrhosis stage I was diagnosed. Therapy with ursodeoxycholic acid (12mg/kg body
      weight/die) was started. Follow-up examinations indicated that cholestatic
      parameters had normalized and antimitochondrial antibodies became negative. In a
      further biopsy of the liver nearly regular liver parenchyma was demonstrated.
      Thus, therapy with ursodeoxycholic acid was stopped. However, in November 1992
      cholestatic parameters increased again and, antimitochondrial antibodies recurred
      (subtype anti-M9: positive) without any clinical symptoms. Ursodeoxycholic acid
      therapy was reintroduced again. Within 3 months cholestatic parameters returned
      to normal and antimitochondrial antibodies were eliminated again. Since then
      ursodeoxycholic acid has been given continuously and a long-term remission as
      defined by clinical, serological and histological criteria could be maintained
      until today. This case report indicates a serological remission and a marked
      histological improvement in a female patient with an early stage of primary
      biliary cirrhosis (stage I) during therapy under ursodeoxycholic acid. It has to
      be discussed whether certain early stages of primary biliary cirrhosis with
      benign antimitochondrial antibody-profile (anti-M9: positive) respond well to
      long-term treatment with ursodeoxycholic acid.

PMID- 15966200
TI  - Prognostic factors and scoring system for survival in colonic perforation.
AB  - BACKGROUND/AIMS: No ideal and generally accepted prognostic factors and scoring
      systems exist to determine the prognosis of peritonitis associated with colonic
      perforation. This study was designed to investigate prognostic factors and
      evaluate the various scoring systems to allow identification of high-risk
      patients. METHODOLOGY: Between 1996 and 2003, excluding iatrogenic and trauma
      cases, 26 consecutive patients underwent emergency operations for colorectal
      perforation and were selected for this retrospective study. Several clinical
      factors were analyzed as possible predictive factors, and APACHE II, SOFA, MPI,
      and MOF scores were calculated. RESULTS: The overall mortality was 26.9%.
      Compared with the survivors, non-survivors were found more frequently in
      Hinchey's stage III-IV, a low preoperative marker of pH, base excess (BE), and a
      low postoperative marker of white blood cell count, PaO2/FiO2 ratio, and renal
      output (24h). According to the logistic regression model, BE was a significant
      independent variable. Concerning the prognostic scoring systems, an APACHE II
      score of 19, a SOFA score of 8, an MPI score of 30, and an MOF score of 7 or more
      were significantly related to poor prognosis. CONCLUSIONS: Preoperative BE and
      postoperative white blood cell count were reliable prognostic factors and early
      classification using prognostic scoring systems at specific points in the disease
      process are useful to improve our understanding of the problems involved.

PMID- 15966199
TI  - Pelvic perfusion for locally recurrent unresectable rectal tumors.
AB  - BACKGROUND/AIMS: Pelvic perfusion evolved as a palliative and curative treatment
      modality for advanced pelvic tumors and literature data support its use in
      different steps of the disease. METHODOLOGY: 15 patients with recurrent rectal
      tumor, without any systemic metastases were included in the study. Mean age was
      49.7 years, 12 males, 3 females. Mean survival was 18 months. RESULTS: 15
      unresectable rectal cancer patients were included in this study. Three (20%)
      complete response, 6 (40%) partial response, 2 stable disease (13.3%) and 4
      (26.7%) progression were seen after pelvic perfusion. Mean survival is 26.54
      months after perfusion (median=10). In multivariate analysis response rate to
      isolated perfusion and tumor size are significant factors effecting survival
      (p<0.05). The patients who did not receive chemotherapy after detection of pelvic
      recurrence did better (p=0.0086). Response to isolated pelvic perfusion (IPP) is
      an important factor for survival of locally advanced rectal tumors in log-rank
      test (p=0.0001). CONCLUSIONS: Isolated pelvic perfusion is a good alternative for
      non-resectable pelvic malignancies and should be considered as an important part
      of the multidisciplinary approach for these tumors.

PMID- 15966201
TI  - Is decrease of tumor volume correlated with stage change after preoperative
      concurrent chemoradiotherapy?
AB  - BACKGROUND/AIMS: The significance of tumor volume and its change after concurrent
      chemoradiotherapy (CCRT) was evaluated. METHODOLOGY: Standard-dose external
      radiation and oral UFUR plus leucovorin were used to treat 30 middle and lower
      rectal adenocarcinoma patients. Volume of tumor calculated from images obtained
      by dynamic MRI of the rectum before and after CCRT was compared to pathological
      results after definite resection and other clinical data. RESULTS: The T-stage in
      15 patients (50%), the N-stage in 13 (72.2%), and overall, the TNM stage in 18
      (60%), were downstaged, including 7 (23.3%) with complete responses (CR). Volume
      of tumor before CCRT (Vpre) and after CCRT (VPost) was 10.3+/-6.1cm3 and 4.2+/
      2.2cm3, respectively, and VPre correlated with initial T stage, N stage, age, and
      location. The net decrease ratio (NDR) of tumor volume was related to Vpre and
      initial T stage. As to the downstaging effect, VPre was related to incidence of
      CR; NDR was related to the downstaging of the N stage. CONCLUSIONS: All tumors
      showed volume reduction after CCRT, but the downstaging benefits were not in
      proportion to the size change. Initially larger tumors had higher ratios of
      volume reduction, and smaller tumors had higher chance of CR.

PMID- 15966202
TI  - Generation of antitumor immunity against large colon tumors by repeated runs of
      electrochemotherapy.
AB  - BACKGROUND/AIMS: Electrochemotherapy, which uses two parallel electrodes for
      delivery of electric pulses, may be useful for treatment of tumor nodules.
      However, in clinical fields, tumors that are larger than the distance between the
      two electrodes are frequently observed, and it would be difficult in such cases
      to deliver electric pulses to the tumor. This study was done to define how host
      antitumor immunity is generated by repeated electrochemotherapy treatments, and
      whether it is associated with regression of even large tumor nodules.
      METHODOLOGY: Balb/c mice and Balb/c nude mice were inoculated subcutaneously with
      colon 26. Electrochemotherapy using bleomycin and electroporation (CUY21) was
      administered as a treatment for tumor nodules that were larger than the distance
      between the electrodes. RESULTS: In Balb/c mice, growth of large tumors at the
      start of treatment is not inhibited by a single electrochemotherapy treatment.
      However, complete tumor regression was obtained through repeated
      electrochemotherapy treatments. No tumor cure was observed among Balb/c nude mice
      under the same therapeutic conditions. Inflammatory cells were accumulated in the
      tumor tissue seven days after the third electrochemotherapy treatment.
      CONCLUSIONS: Repeated electrochemotherapy is a promising treatment, even for
      large tumors, such as are usually encountered in clinical practice, by generating
      T-cell dependent, antitumor immunity.

PMID- 15966203
TI  - Early oral feeding should be resumed following the resolution of gastric ileus.
AB  - BACKGROUND/AIMS: The main aim of the study was to assess the feasibility of early
      mobilization and early feeding following the resolution of gastric ileus in
      patients who have elective open colonic surgery. METHODOLOGY: This was a
      randomized controlled trial of patients who were assigned to one of the following
      two groups. Group 1: patients were encouraged to mobilize postoperatively. A
      radiopaque marker was given orally on the first postoperative morning and X-ray
      film was taken daily until more than 70% of the markers had been emptied out of
      the stomach. Then patients received a diet regardless of flatus or defecation.
      Group 2: patients were not enforced to mobilize and allowed a diet following
      flatus or defecation. RESULTS: No significant differences were noted in age, sex,
      and type of procedures in either group. No patient in group 1 vomited
      postoperatively, while postoperative time to oral diet was significantly shorter
      than that to the resumption of bowel function. No significant difference was seen
      in the incidence of complications. The time to first flatus in group 1 (median,
      48 hours) was significantly shorter than that in group 2 (median, 67 hours). The
      length of hospitalization in group 1 (median, 7 days) was significantly shorter
      than that in group 2 (median, 10 days). CONCLUSIONS: Early mobilization and early
      feeding following the resolution of gastric ileus is safe and feasible without
      vomiting in patients who have elective colonic surgery.

PMID- 15966204
TI  - Persisting perianal ulcer after radiotherapy for anal cancer: recurrence of
      disease or late radiation-related complication?
AB  - We report the case of a 47-year-old HIV-negative male affected by a perianal
      ulcer which occurred after chemoradiation delivered for anal cancer. In spite of
      a negative biopsy the lesion was highly suspected to be a disease recurrence.
      Uncontrollable pain and anal stenosis were also present; abdominoperineal
      resection with a large excision of perianal tissues and reconstruction with
      bilateral musculocutaneous gracilis flaps was therefore performed. Histology did
      not confirm tumor recurrence. Thirteen months after surgery, the patient is still
      alive and free of disease. The introduction of radiotherapy and concomitant
      chemotherapy has revolutionized the treatment of anal cancer, avoiding demolitive
      surgery in a large subset of patients. Radionecrosis is an uncommon but
      potentially devastating event occurring in up to 10% of patients undergoing
      radiotherapy for anal cancer. It causes clinical (pain, anal stenosis, mucositis
      and diarrhea) and diagnostic problems (recurrence vs. benign post-attinic
      lesion). In the present article we review this uncommon complication, discuss the
      technical surgical aspects associated with a very large perianal tissue removal,
      and data of the most recent literature in this field.

PMID- 15966205
TI  - Changes in the histology and function of gastric mucosa and in Helicobacter
      pylori colonization during a long-term follow-up period after vagotomy in
      duodenal ulcer patients.
AB  - BACKGROUND/AIMS: To investigate changes in the histology and the Helicobacter
      pylori (H. pylori) prevalence and density of the gastric mucosa, as well as in
      fasting serum gastrin and serum pepsinogen I, depending on completeness of
      vagotomy, and in cases of recurrent ulcer, during 14 years after operation in
      duodenal ulcer patients. METHODOLOGY: 122 vagotomized duodenal ulcer patients
      were studied twice on average 9 and 14 years after operation. The presence of
      recurrent ulcer and completeness of vagotomy were assessed simultaneously
      endoscopically and by endoscopic Congo red test. The histology of the gastric
      antrum and corpus mucosa was assessed in accordance with the Sydney system. The
      amount of H. pylori in the specimens was detected by microscopic counting;
      gastrin and pepsinogen I in serum were determined radioimmunologically. RESULTS:
      During the 14-year follow-up period, complete vagotomy patients were
      characterized by a smaller amount of active antrum gastritis and a larger amount
      of active chronic corpus gastritis involving corpus atrophy in 46% of cases 14
      years after operation. Recurrent ulcer patients were characterized by a
      significantly higher prevalence of high-grade H. pylori colonization and active
      mucosal inflammation in the antrum as well as by a lower level of active mucosal
      inflammation and atrophy in the corpus and a higher serum pepsinogen I level
      compared with complete vagotomy cases. The data of incomplete vagotomy patients
      without recurrent ulcer became more similar to those recorded for recurrent ulcer
      patients. CONCLUSIONS: In duodenal ulcer patients, changes in the histology of
      the gastric antrum and corpus mucosa as well as in H. pylori prevalence and
      density and in serum pepsinogen I levels are different depending on completeness
      of vagotomy during 14 years after operation.

PMID- 15966206
TI  - Noncardiac chest pain of esophageal origin in patients with and without coronary
      artery disease.
AB  - BACKGROUND/AIMS: Non-cardiac chest pain is a frequent finding in patients
      admitted to emergency departments, and it has been shown that many of these
      patients may have an esophageal cause for their pain. However, little data are
      available on patients primarily referred to the cardiology unit, and especially
      those with coronary artery disease. The purpose of this study was to assess the
      role of esophageal dysfunction in chest pain patients with and without coronary
      artery disease. METHODOLOGY: Eighty-one patients referred from a cardiology unit
      for chest pain and no myocardial infarction entered the study. Sixty-one patients
      had no evidence of coronary artery disease, whereas 20 had coronary artery
      disease with chest pain at rest. After the cardiological evaluation, the patients
      underwent esophageal function testing by means of upper endoscopy, manometry, and
      24-hour pH-monitoring. RESULTS: Overall, 10% of patients (2.5% in the coronary
      artery disease group) had evidence of endoscopic esophagitis, 46% of esophageal
      motor disorders (12% in the coronary artery disease group), and 10% abnormal pH
      monitoring (1% in the coronary artery disease group). CONCLUSIONS: We report that
      the esophagus might be responsible for non-cardiac chest pain in patients with
      and without coronary artery disease. In our experience, esophageal motor
      disorders, and not an increased acid reflux, are the abnormalities most commonly
      found in these patients.

PMID- 15966207
TI  - Survival and clinical evaluation of salvage operation for cervical lymph node
      recurrence in esophageal cancer.
AB  - BACKGROUND/AIMS: Although extended lymphadenectomy for thoracic esophageal cancer
      is widely practiced in Japan, solitary supraclavicular lymph node recurrence
      (SCLR) has often become a problem. This study was designed to evaluate the
      survival and clinical benefit of salvage cervical lymphadenectomy. METHODOLOGY:
      Between 1989 and 2001, 153 patients underwent esophagectomy for esophageal
      cancers. SCLR was identified in 5 (3.7%) patients and these five patients were
      examined retrospectively. RESULTS: Surgical treatment was performed intensively
      for all patients. Two patients showed longterm survival for 7 years 3 months and
      4 years, respectively. Four patients belonged to the good prognostic group but
      the other patient had poor prognosis from the viewpoint of both the pathological
      metastatic lymph node number and disease-free interval (DFI). There were no local
      recurrences but were a recurrent laryngeal nerve palsy in three patients
      associated with treatment. CONCLUSIONS: Salvage cervical lymphadenectomy for SCLR
      should be performed positively by selecting each case carefully. Indication must
      be weighed against increased morbidity considering such indicators as the extent
      of metastatic lymph node numbers and DFI.

PMID- 15966208
TI  - GI flexible endoscope disinfection: "in use" test comparative study.
AB  - BACKGROUND/AIMS: There is some confusion as to the effectiveness of the available
      disinfectants for achieving "high level" disinfection, and the microbiologic
      method to assess the efficacy of the selected disinfectant regime. The "in use"
      method is adequate for control and for establishing comparisons between different
      disinfectants. METHODOLOGY: This study compares the efficacy of the different
      disinfectants and disinfection regimes available, including automatic systems to
      the 20-minute immersion in 20 degrees C 2%-alkaline-glutaraldehyde (AG). After
      cleaning and disinfection the effluent obtained from each channel was collected
      under sterile conditions. A total of 0.1 mL of the effluent was introduced in
      liquid thioglycolate, an additional 0.1 mL was seeded in solid blood agar and in
      MacConkey agar medium, and maintained for 48 hours at 37 degrees C. Thioglycolate
      media turbidity after a 48-hour culture indicates bacterial growth. RESULTS: The
      disinfectants used were 2% AG, 0.125% and 0.27% glutaraldehyde,
      glutaraldehydephenol-phenate, peracetic acid, N-duopropenida, 13%-H2O2-27%-lactic
      acid and ortho-phtalaldehyde using manual and automated methods. Most of the
      disinfectants available obtain similar or better results compared with 20' 2% AG.
      The best results (bacterial reduction greater than 3 log10), were those obtained
      using 20-minute 1/4 or 1/2 glutaraldehydephenol-phenate, 10-minute peracetic
      acid, or hydrogen-peroxide compounds, 5-minute 0.125% and 0.27% AG at high
      temperature and 5-minute 0.5% ortho-phtalaldehyde. CONCLUSIONS: A sensitive
      microbiologic method described may be useful in the control of disinfection and
      allowed: 1) knowledge of the limits of the efficacy of the disinfection methods
      usually used, 2) effective comparison of the different disinfectants and
      disinfection regimes and 3) awareness of the need for microbiologic regulations
      in assessing "high level" disinfection.

PMID- 15966209
TI  - CD14 expression on monocytes and soluble CD14 plasma levels in correlation to the
      promotor polymorphism of the endotoxin receptor CD14 gene in patients with
      inactive Crohn's disease.
AB  - BACKGROUND/AIMS: The association of the single nucleotide polymorphism in the
      promotor of the lipopolysaccharide receptor CD14 gene (T/C at position -159) with
      Crohn's disease has recently been demonstrated. This CD14 polymorphism is a
      potential predisposition factor responsible for inter-individual differing
      inflammatory reactions involving the CD14 receptor. We studied the correlation
      between the CD14 genotype (CC, CT, TT) and the membrane-bound CD14 monocyte
      expression and soluble CD14 in patients with inactive Crohn's disease.
      METHODOLOGY: In 23 patients and 29 healthy volunteers the membrane-bound CD14
      density on unstimulated monocytes and soluble CD14 plasma levels were examined
      using quantitative flow cytometry and enzyme-linked immunosorbent assay. RESULTS:
      In normal controls membrane-bound CD14 monocyte density did not differ
      significantly between the genotypes CC, CT, or TT. In contrast, patients with
      inactive Crohn's disease and genotype TT showed a significantly lower membrane
      bound CD14 density on monocytes compared to patients with genotype CC. Soluble
      CD14 plasma levels were significantly higher in patients with inactive Crohn's
      disease compared to the same genotype of healthy controls, but there was no
      significant difference between the genotypes CC, CT, and TT. CONCLUSIONS: Our
      data show that the membrane-bound CD14 monocyte expression and the soluble CD14
      plasma levels in patients with inactive Crohn's disease completely differ from
      that in healthy individuals. In order to develop individualized therapy
      strategies further studies should be carried out to evaluate whether the TT
      genotype is associated with differences in the clinical course of Crohn's disease
      and in the response to antibacterial treatment.

PMID- 15966210
TI  - Pseudomyxoma peritonei: a clinicopathologic analysis and follow-up of 21
      patients.
AB  - BACKGROUND/AIMS: Pseudomyxoma peritonei is an uncommon disease characterized by
      the presence of mucinous peritoneal implants associated with an abdominal
      neoplasm. Our objective is to consider the characteristics of this entity in our
      western Mediterranean urban population. METHODOLOGY: All cases diagnosed with
      pseudomyxoma peritonei by our hospital during a period of 16 years were reviewed.
      Data from their clinical records and the biopsy samples were analyzed. RESULTS:
      We found 21 cases of pseudomyxoma peritonei with a male/female ratio of 10/11 and
      a mean age of 59 years. The predominant presentation symptom was abdominal pain
      (17 cases, 6 of them with acute abdomen). The most frequent primary site of
      origin of the pseudomyxoma was the appendix (10 cases). The histologic diagnosis
      was malignant (associated with carcinoma) in 17 cases and indeterminate behavior
      in 4. The follow-up was available for 15 patients (mean follow-up of 41 months),
      while six patients have been lost. Nine patients have died during the follow-up
      and the other 6 patients are still alive after follow-up. CONCLUSIONS: Laparotomy
      is the main tool for diagnosing pseudomyxoma peritonei. The appendix is the most
      frequent primary site of origin of pseudomyxoma peritonei, followed by bowel; the
      latter being more important than previously described. In most cases the
      histology is malignant. The prognosis is bad with a mortality greater than 60% at
      5 years.

PMID- 15966211
TI  - Clinical presentation of Crohn's disease. association between familial disease,
      smoking, disease phenotype, extraintestinal manifestations and need for surgery.
AB  - BACKGROUND/AIMS: Recent molecular data suggest that genetic factors may underlie
      the disease heterogeneity observed in Crohn's disease (CD). It was also suggested
      that familial inflammatory bowel disease (IBD) is a homogenous subgroup,
      phenotypically different from sporadic disease. Our aim was to determine the
      clinical presentation in a large CD population. METHODOLOGY: 564 CD patients
      (m/f: 278/286, age: 37.4 (SD 12.7) yrs, duration: 8.4 (7.1) yrs) were included.
      Disease phenotype was determined according to Vienna classification. Familial
      disease, extraintestinal manifestations (EIM), need for surgery and smoking
      habits were also analyzed. RESULTS: Familial IBD was present in 73 (12.9%)
      patients. Age at onset and presence of EIMs was associated with familial disease.
      Penetrating (44.6% vs. <10 yrs: 29.1%, P<0.0001) and ileocolonic disease (54.4%
      vs. 42.8%, P=0.03) were more common in patients with a disease duration of > or
      =10 yrs. In a logistic regression model female gender, colonic/ileocolonic
      location, smoking and familial IBD were independent risk factors for EIMs, while
      ileal and non-inflammatory disease increased the risk for resections. Smoking was
      also associated with frequent relapses. CONCLUSIONS: Familial IBD was associated
      with the presence of EIMs, while ileal involvement and noninflammatory behavior
      independently increased the risk for surgery. Since penetrating and extensive
      disease was more frequent in patients with longer disease duration our data
      support a possible change in location and behavior during the course of disease.

PMID- 15966212
TI  - Laparoscopic-assisted partial ileectomy for crohn's disease associated with
      chronic anemia due to frequent hemorrhage.
AB  - Crohn's disease can involve any part of the gastrointestinal tract. Although good
      conservative treatment is given as soon as possible, most patients with this
      disease will eventually require surgery. We encountered a case of Crohn's disease
      associated with anemia which we treated with laparoscopic-assisted ileectomy. The
      postoperative course was satisfactory. The most important characteristic of
      Crohn's disease, fat wrapping and extending over the serosal surface toward the
      antimesenteric border, was observed in the ileum, distinguishing the disease and
      pinpointing the lesion accurately. This surgical method has an advantage over
      open surgery in that the recovery time is shorter and incisions are smaller,
      allowing easier surgery in the future, shortening the patient's hospital stay,
      and improving the patient's quality of life.

PMID- 15966213
TI  - Is imatinib justified as an adjuvant chemotherapy for patients with recurrent
      gastrointestinal stromal tumors.
AB  - Imatinib, an inhibitor of the tyrosine kinase activity of c-kit, was used as an
      adjuvant chemotherapy in two patients who underwent curative surgery for
      recurrent gastrointestinal stromal tumors. One patient has maintained tumor-free
      survival for 12 months, while the other had rapid recurrence and metastasis of
      tumors 3 months after he discontinued the drug. The indication and effects of
      imatinib for prevention of recurrence of GIST after ablative surgery were
      discussed.

PMID- 15966215
TI  - Effect of follistatin on rat liver regeneration and tumor growth after portal
      occlusion.
AB  - BACKGROUND/AIMS: Although follistatin is known to be a positive regulator in
      liver regeneration after hepatectomy, the effects of follistatin on regeneration
      following portal occlusion and on tumor growth are not known. METHODOLOGY: In
      experiment 1, rats were injected with follistatin immediately following 70%
      hepatic resection (HR), ligation of the left portal vein (PVL), or ligation of
      the left hepatic artery (HAL). Hepatic regenerative activity then was determined.
      In experiment 2, rats were injected intraportally with AH130 tumor cells. At 7
      days after injection, the same procedures were carried out as in experiment 1. In
      a third experiment, in vitro, AH130 cells were cultured with various
      concentrations of activin A or follistatin, and cell proliferation was assessed.
      RESULTS: In experiment 1, follistatin did not accelerate liver regeneration after
      PVL. In experiment 2, follistatin significantly increased liver weight after HR,
      but did not accelerate tumor growth in any group. In vitro, neither follistatin
      nor activin affected proliferation of tumor cells. CONCLUSIONS: The mechanism of
      liver regeneration after PVL appears to differ from that after HR. Follistatin
      acts as a growth promoter for hepatocytes, but not for cancer cells.

PMID- 15966214
TI  - Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases
      of GISTs.
AB  - There has been little research evaluating changes related to tumor cell
      proliferation between primary and metastatic tumors of gastrointestinal tumors in
      the same case. We herein report the case of a 50-year-old woman with a gastric
      gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors
      three times in the 7 years after proximal gastrectomy for GIST. The primary and
      all the metastatic liver tumors, except the second, showed fascicular/storiform
      architecture and the short spindle cell type. The diffuse epithelioid cell
      proliferation was observed in the second metastatic liver tumor. Although the
      immunostaining pattern with respect to GIST differentiation markers had been
      preserved in the primary tumor as well as in all of the metastatic tumors, the
      latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The
      primary tumor showed diffuse positive p53, and the highest value of Ki-67
      labeling index (LI) among them. The metastatic liver tumors showed focal,
      negative or sporadic positive appearances of p53, however, Ki-67 LI were
      scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might
      be useful for evaluating changes related to tumor cell proliferation between
      primary and metastatic tumors of GISTs.

PMID- 15966217
TI  - Comparative analysis of postoperative morbidity according to type and extent of
      hepatectomy.
AB  - BACKGROUND/AIMS: The aim of our retrospective study was to compare the factors
      contributing to postoperative complications according to the extent of
      hepatectomy. METHODOLOGY: We examined 166 patients with hepatobiliary carcinoma
      who underwent hepatectomy. Patients were divided into three groups according to
      the type and extent of hepatectomy: 1) left lobectomy (n=27), 2) right lobectomy
      or posterior segmentectomy (n=55) and 3) other hepatectomies (n=84). Patient
      demographics, major complications (infection, ascites, pleural effusion,
      atelectasis, static symptoms of the stomach, biliary leakage and hepatic failure)
      after hepatectomy were analyzed. RESULTS: In patients with obstructive jaundice,
      lobectomy was the most commonly performed operation due to the extent of tumor
      along the main hepatic duct. Prolonged ascites or massive pleural effusion was
      frequently observed after right lobectomy (p=0.001) and posterior segmentectomy
      (p=0.002). However, the incidences of these complications were similar in
      patients with chronic viral hepatitis. Symptoms related to gastric stasis and
      biliary leakage were significantly more common after left lobectomy than other
      surgeries. The incidence of hepatic failure was higher (p<0.05) after major
      hepatectomy, particularly right lobectomy, than other surgeries. CONCLUSIONS: Our
      results emphasize the need to understand characteristics of specific
      complications occurring after different types of hepatic resection surgery to
      prevent post-hepatectomy complications.

PMID- 15966216
TI  - Inhibitory effects of safe and novel SOD derivatives, galactosylated-SOD, on
      hepatic warm ischemia/reperfusion injury in pigs.
AB  - BACKGROUND/AIMS: Oxygen-derived free radicals such as superoxide play an
      important role in ischemia/reperfusion (IR) injury during and after extensive
      liver surgery or liver transplantation. Superoxide dismutase (SOD) has protective
      effects against hepatic IR injury. The effect of native SOD is, however, limited
      because of rapid elimination from the blood circulation and poor affinity for
      liver cells. It was reported by our collaborators that a SOD derivative modified
      with galactose (Gal-SOD) was selectively delivered well to hepatocytes by direct
      attachment to galactose receptors. In the present study, the efficacy of this
      agent for attenuating hepatic warm IR injury was investigated using the pig
      model. METHODOLOGY: After 45-min clamping of the hepatic artery and portal vein,
      pigs were divided into 3 groups according to the following treatments. Ten
      milliliters of normal saline in Group 1 (n=5), 10,000 units/kg of native SOD in
      Group 2 (n=5) and 10,000 units/kg of Gal-SOD in Group 3 (n=5) were given just
      prior to hepatic reperfusion. Liver function including clearance of total bile
      acid (TBA) and hyaluronic acid (HA) was investigated. Lipid peroxidase of the
      liver tissue (LPO) and histological findings were examined. In addition, survival
      rates of the pigs in each group were evaluated. RESULTS: The survival rates at
      the 7th day after the operation were 60%, 80%, 100% in Groups 1, 2 and 3,
      respectively. Liver function tests, clearance of TBA and HA, and LPO levels were
      significantly improved in Groups 3 over findings in Groups 1 and 2. Congestion of
      hepatic tissues and vacuolization of hepatocytes in Group 3 were less than those
      in Groups 1 and 2. These results suggested that oxygen-derived free radicals were
      scavenged by Gal-SOD and IR injury was attenuated. CONCLUSIONS: A safe and novel
      agent, Gal-SOD has a protective effect against hepatic warm IR injury.

PMID- 15966218
TI  - Laparoscopic fenestration of symptomatic non-parasitic cysts of the liver.
AB  - BACKGROUND/AIMS: The use of laparoscopic technique for management of symptomatic
      liver cysts is documented to be a feasible and safe procedure with proved
      symptomatic relief. In the present study, we reviewed the results of this
      approach in the management of symptomatic liver cysts. METHODOLOGY: Retrospective
      review of all patients with symptomatic liver cysts that were treated by
      laparoscopic fenestration in our department over a 3-year period from 1999 to
      2001. RESULTS: Ten patients were treated using a laparoscopic approach. All
      patients achieved short-term alleviation of symptoms and an uneventful
      postoperative course. The mean hospital stay was 3 days. Long-term follow-up (24
      months) was available for all the patients. In all the patients, there was no
      clinical and radiographical recurrence. CONCLUSIONS: The present study confirms
      that relief of symptoms can be achieved with the laparoscopic approach for non
      parasitic liver cysts. Omental packing is not necessary to prevent recurrence of
      simple hepatic cysts.

PMID- 15966219
TI  - Transcatheter management for multiple liver tumors after hepatic artery
      obstruction following reservoir placement.
AB  - BACKGROUND/AIMS: Hepatic arterial infusion chemotherapy via an implantable port
      system has been widely used to treat unresectable liver neoplasms. Complications
      of the hepatic artery occlusion following reservoir placement, however, makes it
      impossible to continue the infusion therapy. The purpose of our study was to
      assess the possibility of transcatheter treatment after the hepatic artery
      obstruction following reservoir placement. METHODOLOGY: Between April 1999 and
      May 2002, 14 patients with liver tumors had the complication of hepatic artery
      obstruction following reservoir placement. We conducted a prospective trial to
      assess 1) the collateral pathways of feeding artery using angiography, 2) the
      possibility of transcatheter treatment or 3) re-reservoir placement for liver
      tumors. RESULTS: 1) Angiography revealed that the main collateral pathway of the
      feeding artery was the inferior phrenic artery in 7 patients (50%), the dorsal
      pancreatic artery in 4 patients (29%) and the anastomotic branch of the celiac
      axis in 1 patient (7%). The main collateral pathway could not be detected in 2
      patients (14%). 2) Transcatheter treatment was successfully performed in all
      patients (100%). 3) Rereservoir placement failed in all cases. CONCLUSIONS: These
      results suggest that transcatheter treatment may be possible for patients with
      hepatic artery obstruction.

PMID- 15966220
TI  - Serum acute-phase protein level as indicator for liver failure after liver
      resection.
AB  - BACKGROUND/AIMS: We investigated the relationship between postoperative liver
      failure and serum acute-phase protein level before and after liver resection.
      METHODOLOGY: Thirty-four patients who underwent liver resection were
      prospectively included. Serum concentrations of negative (albumin, prealbumin and
      retinol-binding protein) and positive (orosomucoid, haptoglobin and C-reactive
      protein) acute-phase proteins were assayed prior to surgery (baseline) and on
      postoperative day 3, 12 and 45. Postoperative liver failure was defined as serum
      bilirubin more than 50 micromol/L or prothrombin time less than 50% on
      postoperative day 7. Univariate analysis was performed to compare patients who
      did and did not present postoperative liver failure. RESULTS: Postoperative liver
      failure occurred in 8 cases and was correlated with: 1) higher negative and lower
      positive acute-phase protein levels (p<0.04) at baseline, 2) lower negative and
      lower positive acute-phase protein levels on postoperative day 3, 12 or 45 (p< or
      =0.05). CONCLUSIONS: Early onset of inflammatory serum protein profile was
      correlated with absence of postoperative liver failure. Serum acute-phase protein
      could be used as predictor as well as early postoperative diagnosis marker of
      postoperative liver failure. Relationship between preoperative inflammation and
      postoperative liver failure warrants further investigations because of potential
      therapeutic consequences.

PMID- 15966221
TI  - A novel intrahepatic arterial chemotherapy after radical resection for advanced
      hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with portal vein
      invasion and/or intrahepatic metastasis has an unfavorable prognosis even after
      radical hepatic resection. The aim of this study was to evaluate the
      effectiveness of a novel postoperative adjuvant chemotherapy given through the
      hepatic artery and based on biochemical modulation using cisplatin (CDDP) and 5
      fluorouracil (5-FU). METHODOLOGY: Fifteen patients with advanced HCC with portal
      vein invasion into the main trunk and/or intrahepatic metastases of more than 3
      segments were included in this study. After radical hepatic resection, the
      patients were divided to two groups: the adjuvant chemotherapy group (n=7) given
      the novel arterial infusion regimen with CDDP and 5-FU, and the control group
      (n=8) given no adjuvant chemotherapy. RESULTS: Three-year survival rate of the
      adjuvant chemotherapy group tended to be significantly longer compared to that
      for the control group (p < 0.05). Most of the tumor recurrence was in the remnant
      liver, 5 cases in both of the groups. Significant difference of the recurrence
      patterns was recognized, rather than difference of the disease-free survival rate
      between the two groups. All of the intrahepatic recurrences are multiple in the
      control group, but in the adjuvant chemotherapy group, 2 cases of the recurrences
      showed a localized tumor surgically resected. It is noteworthy that the
      occurrence of multiple recurrence was significantly later in the adjuvant
      chemotherapy group compared to the control group (18.9 months vs. 6.5 months;
      p<0.05). CONCLUSIONS: Our data suggest that this novel adjuvant chemotherapy can
      improve the postoperative prognosis of patients with the advanced HCC.

PMID- 15966222
TI  - Correlation between drainage area volume of middle hepatic vein and liver
      function.
AB  - BACKGROUND/AIMS: Complete outflow is impossible to maintain on both sides in
      donors undergoing hemi-liver graft harvesting, because the middle hepatic vein
      (MHV) can be preserved on only one side. The area in which outflow veins are
      disrupted becomes congested, and does not sufficiently regenerate. METHODOLOGY:
      The subjects of the study were 55 living donors who provided the left liver with
      caudate lobe, including the MHV. The midpoint between the tributaries of the MHV
      and the right hepatic vein was determined preoperatively with computed
      tomography. The midpoint between the tributaries of the MHV and right hepatic
      vein and the borderline between the right and left liver were used to predict the
      MHV drainage area volume. Total bilirubin levels, the prothrombin time
      international normalization ratio, and alanine aminotransferase were measured in
      donors on postoperative days 1, 3, 5 and 7. RESULTS: The parameters that
      correlated with the MHV drainage area volume included total bilirubin on days 5
      and 7, prothrombin time international normalization ratio on day 3, and alanine
      aminotransferase on day 7. CONCLUSIONS: Middle hepatic vein drainage area volume,
      calculated using the present method, correlated with early liver function after
      left liver harvesting with the MHV.

PMID- 15966223
TI  - Modified diagnostic criteria of drug-induced liver injury proposed by the
      international consensus meeting.
AB  - BACKGROUND/AIMS: The usefulness of the diagnostic criteria of the International
      Consensus Meeting (criteria A) has been previously reported. However, these
      criteria are not clinically adaptable in Japan where allergic reaction is one of
      the major etiologies of drug-induced liver injury and thus it was revised and
      reported in the Digestive Disease Week-Japan of 2002 as DDW-J criteria (criteria
      B). It remains controversial whether the revised criteria can exclude drugs not
      causing liver injury. METHODOLOGY: Two new diagnostic criteria (criteria C and D)
      were designed to supplement the DDW-J criteria. Usefulness and limitations of the
      four criteria were retrospectively examined using cases of drug-induced liver
      injury experienced in 8 hospitals. RESULTS: It was confirmed that the sensitivity
      of criteria B is excellent for diagnosis of drug-induced liver injury. However,
      diagnostic criteria B were found to be disadvantageous in relation to
      specificity, while diagnostic criteria D were disadvantageous in relation to
      sensitivity. Sensitivity of diagnostic criteria C was a little superior to that
      of diagnostic criteria A. CONCLUSIONS: On the basis, the significant sensitivity
      of criteria B was confirmed again, however, modification should be done for
      increasing specificity. Criteria C appear to be the best for their sensitivity
      and specificity.

PMID- 15966224
TI  - Expression of matrix metalloproteinase 7, laminin and type IV collagen-associated
      liver metastasis in human colorectal cancer: immunohistochemical approach.
AB  - BACKGROUND/AIMS: Matrix metalloproteinase 7 (MMP-7) plays an important role in
      vessel invasion and metastasis in human colorectal cancer. METHODOLOGY: The
      significance of MMP-7, laminin and type IV collagen expression in human
      colorectal cancer was investigated by immunohistochemical assay, and the
      correlation with liver metastasis was analyzed. RESULTS: In a synchronous
      metastasis group, 26 of 36 cases (72%) showed positive staining of MMP-7: There
      were 32 cases (89%) in the lymph channel and 28/32 cases (87%) in the vessels,
      and 17/34 cases (50%) showed a positive rate of laminin. In the metachronous
      metastasis group, 14 of 30 cases (47%) showed positive staining of MMP-7: There
      were 19 cases (63%) in the lymph channel and 13/19 cases (69%) in the vessels,
      and 17/30 cases (57%) showed a positive rate of laminin. In the control group,
      which was a 5-year disease-free group, despite there being no significant
      clinicopathological factors compared with the other two groups, 17 of 37 cases
      (51%) showed positive staining of MMP-7: There were 12 cases (37%) in the lymph
      channel and 6 cases (18%) in the vessels, and 2/31 cases (5%) showed a positive
      rate of laminin. The expression of type IV collagen attenuated in 19 out of 32
      cases (59%) in Group S, 10 out of 19 cases (53%) in Group M, and 14 out of 37
      cases (38%) in Group C, with no significant differences among the groups. Thus,
      the metastatic groups were significantly higher than the control group in terms
      of expression of laminin and MMP-7 in the lymph channel. CONCLUSIONS: These
      findings suggest that laminin and the expression of MMP-7 in the lymph channel is
      a useful parameter for predicting liver metastasis.

PMID- 15966225
TI  - Hepatocellular carcinomas do not compromise quantitative tests of liver function.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma, which usually develops in cirrhotic
      livers, is one of the most frequent cancers worldwide. If and how far hepatoma
      growth influences liver function is unclear. Therefore, we compared a broad panel
      of quantitative tests of liver function in cirrhotic patients with and without
      hepatocellular carcinoma. METHODOLOGY: Patients with (n=40) and without (n=40)
      hepatocellular carcinoma were matched according to Child-Pugh grade and subjected
      to testing of aminopyrine demethylation capacity, galactose elimination capacity,
      sorbitol clearance and indocyanine green clearance. RESULTS: Compared to healthy
      controls, patients with cirrhosis Child-Pugh grade B and grade C revealed reduced
      metabolic (aminopyrine demethylation capacity, galactose elimination capacity)
      and perfusion-dependent QTLF (sorbitol clearance, indocyanine green clearance).
      Comparing values of quantitative tests of liver function in matched patients with
      and without hepatocellular carcinoma, no differences in liver function parameters
      were observed. CONCLUSIONS: Quantitative tests of liver function correlated
      inversely with the Child-Pugh grade. Since these parameters are not affected by
      the occurrence of hepatocellular carcinoma, the emergence of hepatic neoplasia in
      cirrhotics does not appear to be determined by the degree of hepatic functional
      deterioration.

PMID- 15966226
TI  - Attenuation of graft injury in porcine liver transplantation from non-heart
      beating donor by FR167653.
AB  - BACKGROUND/AIMS: Orthotopic liver transplantation (OLTx) from non-heart beating
      donor (NHBD) often involves hepatic warm ischemia and reperfusion injury which is
      triggered by the inflammatory cytokines. This study was carried out to
      investigate whether a newly synthesized cytokine suppressive anti-inflammatory
      agent, FR167653, attenuates graft injury in OLTx from NHBD. METHODOLOGY: Porcine
      OLTx from NHBD was performed. No-heart beating time was scheduled to be 60
      minutes. Animals were divided into two groups: no treatment control (CT) group
      (n=5), and FR167653 treated (FR) group (n=5), in which FR167653 was administered
      intravenously before the aortic cross clamp in the donor, and before and after
      the hepatic allograft reperfusion in the recipient continuously. RESULTS: Four
      out of five pigs died within 24 hours and one on postoperative day 1 from graft
      liver failure in the CT group, while two pigs died on day 3, and three survived
      more than 7 days in the FR group (p<0.05). Microcirculatory disturbance was
      attenuated, liver injury was lessened, and ATP resynthesis was enhanced in the FR
      group. Additionally, FR167653 inhibited neutrophils infiltration in the liver
      tissue, and suppressed release of inflammatory cytokines after OLTx from NHBD.
      CONCLUSIONS: The treatments with FR167653 successfully prevented graft injury
      after OLTx from NHBD by means of improvement of liver microcirculation, and
      attenuation of neutrophils activation. The inhibitory effect of FR167653 on the
      release of inflammatory cytokines played an important role in the liver graft
      protection.

PMID- 15966227
TI  - Prediction of viremia for cases of hepatitis C virus (HCV) infection using a
      third-generation anti-HCV enzyme immunoassay test.
AB  - BACKGROUND/AIMS: Positive results for anti-hepatitis C virus (HCV) testing reveal
      subjects are infected by HCV, with presence of HCV RNA indicating persistent
      infection. In this study, we attempted to evaluate the validity of the HCV
      viremia using a commercially available, third-generation anti-HCV test.
      METHODOLOGY: Sample rate/cut-off rate (S/CO) ratios for 1,907 anti-HCV-positive
      tests (S/CO >1, AxSYM HCV 3.0; Abbott, IL, USA), which had been performed during
      the last three years, were retrospectively analyzed. Cases with S/CO values
      between 1 and 100 were divided into 20 groups according to S/CO range (in
      increments of 10) and ALT (normal or elevated). Ten random cases were obtained
      for each of the 20 groups. If cases in any group numbered < or =10, all were
      recruited. Totally, 193 cases were enrolled for HCV RNA detection (COBAS
      Amplicor; Roche Diagnostics, NJ, USA). RESULTS: The S/CO distribution was
      biphasic, with two S/CO peaks in the ranges 1-10 (10.7%) and 81-90 (24.2%).
      Regardless of the ALT level, all samples with S/COs < or =10 were negative for
      HCV RNA. Of the samples with S/CO values >10, the optimal cut-off was 40 with
      sensitivity and specificity for both of 81%. In conclusion, subjects with S/CO
      values < or =10 (10.7%) were more likely to be cases of past infection or of non
      specific reaction. Most (90%, 108/120) of the subjects with S/COs >40 represent
      current or persistent infection. To predict viremia in subjects with S/COs
      between 10 and 40, 6.7% of all anti-HCV-positive subjects was invalid by a cross
      sectional observation. CONCLUSIONS: Follow-up or further study is recommended.
      The third-generation EIA test plays a semiquantitative role for the prediction of
      viremia in HCV infection.

PMID- 15966228
TI  - Functional restoration of cirrhotic liver after partial hepatectomy in the rat.
AB  - BACKGROUND/AIMS: Although cirrhosis is the terminal stage of various liver
      diseases, thanks to recent advances one might eliminate some causes of liver
      damage. Liver has a potent regeneration capacity. It is important to evaluate the
      regenerating cirrhotic liver after partial hepatectomy, morphologically and
      functionally, in the long term. METHODOLOGY: We evaluated the functional capacity
      of the rat liver rendered cirrhotic by orally administered thioacetamide, and
      examined the correlation between morphological and functional restoration after
      2/3 hepatectomy in comparison with hepatectomized normal rats and sham-operated
      cirrhotic rats. Morphological restoration was evaluated by remnant liver weight,
      proliferating cell nuclear antigen labeling index, and fibrosis ratio. Functional
      restoration was evaluated by the indocyanine green disappearance rate and
      aminopyrine clearance. RESULTS: Cirrhotic rats were functionally deteriorated in
      comparison with the normal rats. Morphological restoration in cirrhotic rats was
      delayed in comparison with normal rats. Functional restoration after 2/3
      hepatectomy was advanced in comparison with morphological restoration. In
      comparison with sham-operated cirrhotic rats, functional restoration of the
      cirrhotic liver was accelerated by partial hepatectomy. CONCLUSIONS: In cirrhotic
      rats, functional restoration of the liver after 2/3 hepatectomy was advanced in
      comparison with morphological restoration. Partial hepatectomy seemed to promote
      functional restoration of the cirrhotic liver.

PMID- 15966229
TI  - Hepatocellular carcinoma in the youth. A comparative analysis with hepatocellular
      carcinoma in adulthood.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a very rare disease among
      young individuals. Epidemiological, clinical and histopathological features of
      this malignancy in the youth have not been thoroughly studied. METHODOLOGY: A
      review of the clinical files of patients with HCC younger than 40 years of age,
      who were treated between May 1990 and July 2002, was performed. RESULTS:
      Seventeen patients were included for analysis; nine were female and eight male.
      The mean age at diagnosis was 24 years (range 12-39 years). Abdominal pain was
      the main symptom, followed by vomiting and nausea. Enlargement of the liver was
      observed in 11 patients (65%). In seven patients (41%), an etiological factor was
      not found. Five of these cases were of the fibrolamellar variant (29%). Only four
      patients were resected (23%) two of which belonged to the fibrolamellar type.
      Three patients (18%) are still alive after 64.9 months of follow-up. CONCLUSIONS:
      HCC is a very uncommon disease in the youth and affects similarly both genders.
      It is discovered at an advanced stage. Hepatitis B and C are uncommon etiological
      factors. The frequency of fibrolamellar carcinoma is higher in this age group.
      Though resection is more feasible, the overall survival rates remain low.

PMID- 15966230
TI  - Hepatocellular carcinoma confined to Couinaud segment VIII: experience with
      extensive or limited resection.
AB  - BACKGROUND/AIMS: Surgical treatment of hepatocellular carcinoma (HCC) confined to
      Couinaud segment VIII has been regarded as difficult. This study evaluates
      surgical and oncological results after extensive or limited resection of the
      tumor(s). METHODOLOGY: Of the 399 HCC patients that underwent hepatic resection,
      36 patients had the tumor(s) confined to segment VIII. These 36 patients were
      divided into group 1 (extensive resection) (n=15) (three right hepatectomies, 12
      anterior segmentectomies) and group 2 (limited resection) (n=21) (11
      subsegmentectomies, 10 wedge resections). Data were collected prospectively and
      analyzed retrospectively. RESULTS: Hospital mortality and morbidity were 0% and
      20% in group 1, 9.5%, and 38% in group 2 (P>0.05). Group 1 patients had larger
      tumor (4.0cm vs. 2.8cm; P=0.01), heavier resected specimen (380g vs. 118g;
      P<0.01), and a higher incidence of wide surgical margin (> or =1cm) (67% vs. 29%;
      P=0.041) than those in group 2. The percentage of patients in whom the a
      fetoprotein levels returned to the normal range after resection was higher in
      group 1 (75.0%, 6 of 8 patients) than in group 2 (26.7%, 4 of 15 patients)
      (P=0.037). The 1-, 3-, and 5-year disease-free survival in group 1 (93%, 79% and
      52%) were significantly better than those of group 2 (67%, 38% and 22%)
      (P=0.021). CONCLUSIONS: In selected patients, extensive resection of HCC located
      in segment VIII correlates with better survival.

PMID- 15966231
TI  - Two-stage hepatectomy for multiple bilobular liver metastases from colorectal
      cancer.
AB  - BACKGROUND/AIMS: To determine an appropriate surgical treatment for patients with
      multiple liver metastases, we evaluated the efficacy of two-stage hepatectomy in
      patients with multiple bilobular liver metastases from colorectal carcinoma.
      METHODOLOGY: Some patients with multiple liver metastases are not candidates for
      a complete resection by a single hepatectomy, even when downstaged by
      chemotherapy, after portal embolization. In two-stage hepatectomy, the highest
      possible number of tumors is resected in a first, noncurative intervention, and
      the remaining tumors are resected after a period of liver regeneration. Two-stage
      hepatectomy was performed in 11 patients. RESULTS: Two-stage hepatectomy was
      feasible in all of the 11 patients. In 3 of them, the first stage was a major
      resection (more extensive than a lobectomy). This first hepatectomy was
      uneventful in all patients. The second hepatectomy was also uneventful in nine
      patients, but in one of the other two, a perihepatic fluid infection occurred,
      and in the other, postoperative liver failure developed due to a right subphrenic
      abscess. However, all patients were discharged. The percentage of the expected
      resection volume at one time, calculated from CT volumetry, was 75.5+/-1.2% and
      the prognostic score as surgical risk was 56.6+/-4.5. In two-stage hepatectomy
      cases, the percentage of the resected volume and the prognostic score in the
      first hepatectomy were 25.4+/-6.4% and 6.7+/-7.3, and in the second, 45.7+/-4.5%
      and 28.5+/-5.8. During the follow-up procedures, a residual hepatic recurrence
      was observed in 6 patients, and pulmonary recurrence in 9. The 1- and 3-year
      survival rates after the first hepatectomy were 90% and 45%, with median
      survivals of 18 months from the first hepatectomy. CONCLUSIONS: Two-stage
      hepatectomy is a surgical modality intended for patients with initial
      unresectable metastases. However, following such surgery, protective treatment
      against residual liver recurrence and lung metastasis will be a most important
      issue.

PMID- 15966232
TI  - Our experiences with saphenoperitoneal shunts in the treatment of intractable
      ascites.
AB  - Because of significant expenses and complication rates of traditional pumps
      (LeVeen, Denver, Agishi) used in the surgical treatment of refractory ascites a
      simple and cheap operative method has to be found. In saphenoperitoneal shunts
      the one-way flow is maintained by biologically given double saphenous valves. In
      our department 11 saphenoperitoneal shunts have been performed on 9 patients (2
      female, 7 male) in the past one and a half years. Their ascites have been
      associated with cirrhosis of the liver (secondary to aethylism in 8, to HBV
      infection in 1). During the follow-up period significant reduction in body weight
      and abdominal girth, and increase in diuresis with standard diuretics were seen
      in 6 patients. The minor complications (3 seromas, 3 hematomas, 2 cellulitis)
      have been self-limiting in general. In the presence of major complications (1
      peritoneal reflux, 1 severe hypoproteinaemia, 3 shunt occlusion) interventions
      were needed several times. In one of the occlusions contralateral fistula was
      created with PTFE prosthesis implantation, in another case desobliteration
      happened with a silicone drain left in the shunt. The saphenoperitoneal shunts
      could improve quality of life significantly in successful instances with minimal
      negative operative effects without the adverse effects of insertion of foreign
      material.

PMID- 15966233
TI  - Hemophagocytic syndrome after living-donor liver transplantation for fulminant
      liver failure: a case report.
AB  - Hemophagocytic syndrome (HPS) is a hypercytokinemia caused by activated T
      lymphocytes and macrophages in immunologically compromised patients. We report a
      37-year-old female who was diagnosed with HPS after undergoing living-donor liver
      transplantation (LDLT) for fulminant liver failure of unknown etiology. After
      liver transplantation, recipients with pancytopenia should be tested for serum
      ferritin. When the serum ferritin is abnormal, the bone marrow should be biopsied
      to screen for HPS as soon as possible. If the condition is caught early and
      promptly treated, the outcome of this devastating condition might be improved. In
      addition, HPS should be ruled out in LDLT candidates with acute liver failure
      before their operations.

PMID- 15966234
TI  - Long-term quality of life following pancreaticoduodenectomy.
AB  - BACKGROUND/AIMS: This study examined long-term quality of life in an unselected
      consecutive cohort of patients undergoing pancreaticoduodenectomy, both Whipple
      and total, for benign and malignant disease. METHODOLOGY: Forty consecutive
      patients who underwent pancreaticoduodenectomy over a nine-year period formed the
      study group. The control group consisted of 58 age- and sex-matched patients
      undergoing open cholecystectomy during the same period. Quality of Life was
      assessed using the European Organisation for Research and Treatment of Cancer QLQ
      C30 (core cancer module) and QLQ-PAN26 (pancreatic cancer module) questionnaires
      at a median of 42 months postoperatively. RESULTS: The Global Health Status of
      the study and control groups was similar, but significant differences were noted
      in certain individual scales. The benign group reported greater social and
      financial difficulties, and symptoms consistent with impaired exocrine function.
      The malignant group reported difficulties with daily physical and role
      functioning, concern for future health and individual symptoms such as fatigue,
      muscle weakness, and inability to gain weight. CONCLUSIONS: This study
      demonstrates that the overall quality of life of patients who underwent
      pancreaticoduodenectomy compared favorably with that of a control group.
      Significant differences did exist in some individual scales, in both the benign
      and malignant sub-groups, suggestive of exocrine insufficiency.

PMID- 15966235
TI  - Successful pancreatoduodenectomy for carcinoma of the ampulla of vater after
      esophagectomy with remnant gastrectomy.
AB  - A 59-year-old man was admitted to our hospital because his serum hepatobiliary
      enzymes were elevated on the medical check-up in September 2003. In his past
      history, he had undergone distal gastrectomy for a gastric adenoma 17 years
      before. Furthermore, he had undergone subtotal esophagectomy with remnant
      gastrectomy, the right colon and ileum were used for the reconstruction, and a
      cervical esophago-ileostomy and an abdominal colo-duodenostomy were made in the
      fashion of an interposition. Duodenoscopy was performed and showed the protruded
      lesion of the ampulla of Vater, biopsied specimens from this tumor revealed
      adenocarcinomas. Accordingly, we performed pancreaticoduodenectomy with regional
      lymph nodes dissection. The problem in this case was that the rt middle colic
      artery (MCA), and the middle colic vein (MCV) tend to be injured because these
      vessels are situated near the caudal region of the pancreas. We were able to
      identify the superior mesenteric vein (SMV) safely due to approaching this vein
      from the flank and mobilizing the duodenum, dissecting behind the mesenteric
      trunk from right to left. Double cancer of the ampulla of Vater and the esophagus
      are extremely rare, with only 4 cases reported. And we recommended the use of the
      dorsal approach to the SMV to avoid injuring the MCV such as in this case.

PMID- 15966236
TI  - Solid and cystic tumor of the pancreas with massive hemoperitoneum.
AB  - A case of a solid cystic tumor (SCT) of the pancreas with massive hemoperitoneum
      occurring in a 31-year-old woman is reported. She was admitted with abdominal
      pain and rebound tenderness. Computed tomography (CT) disclosed a large tumor
      consisting of both solid and cystic components in the body of the pancreas.
      Within 12 hours after admission, she exhibited exacerbation of pain and
      hemoperitoneum on CT with deterioration of general condition and anemia. Celiac
      artery angiography demonstrated the tumor as a hypovascular mass. SCT of the
      pancreas was suspected, and emergent laparotomy was performed. In the surgical
      procedure, tumor in the body of the pancreas with rupture was detected. Distal
      pancreatectomy was performed with removal of the regional lymph nodes. There was
      no evidence of metastatic disease in the abdomen. The cut surface of the tumor
      exhibited areas of cystic degeneration containing hemorrhagic friable materials.
      Microscopically, the tumor cells were mainly cubic or cylindrical peripherally in
      pseudo-papillary formation. Postoperative recovery was normal and she was
      discharged on the 15th postoperative day. Three years after operation, she is
      free of disease without findings of recurrence.

PMID- 15966237
TI  - Exceptional ultra-late recurrence of papilla Vater carcinoma after
      pancreaticoduodenectomy: two cases at 17 and 25 years.
AB  - Curative resection does not always equate with long-term survival. Cancer of the
      papilla Vater can remain clinically quiescent for decades prior to regional or
      distant recurrence. Nevertheless, late and ultra-late recurrence (respectively 10
      and 15 years after initial treatment) are exceptional events. This protracted
      disease-free interval challenges the concept of a "cure" for cancer of the
      papilla Vater. In the first case reported here, a 74-year-old female underwent
      pancreaticoduodenectomy in 1985 for cancer of the papilla Vater revealed
      histologically as a well-differentiated papillotubular adenocarcinoma, stage IA
      (UICC classification). Multiple hepatic recurrences were found 17 years after the
      operation; hepatic biopsy showed histologically well to moderately differentiated
      papillotubular adenocarcinoma. She died about 17.5 years after the original
      operation. The second case is that of an 82-year-old female who underwent
      pancreaticoduodenectomy in 1974 for cancer of the papilla Vater, histologically a
      well-differentiated adenocarcinoma, stage IA. In the 25.5 years after the
      operation, the cancer recurred at the choledochoduodenal anastomosis and involved
      the liver hilus. Autopsy showed histologically well to moderately differentiated
      adenocarcinoma at the locations indicated, together with lung and lymph node
      metastases. The ultra-late recurrences (>15 years) in these cases are highly
      exceptional and, to our knowledge, this is the first report of such recurrences
      in cancer of the papilla Vater. It can occur in any patient, with or without
      identifiable risk factors. Because cancer of the papilla Vater can recur in many
      prognostically favorable cases after prolonged disease-free intervals, the
      possibility of delayed recurrence should not be ignored.

PMID- 15966238
TI  - Arginine and proline alleles of the p53 gene are associated with different
      locations of gastric cancer.
AB  - BACKGROUND/AIMS: Abnormal function of gene p53 is associated with the formation
      of various cancers including gastric cancer. Recently, p53 codon 72 polymorphism
      was extensively studied to determine the risk factors responsible for cancer
      formation using the concept of single nucleotide polymorphism. In this study, we
      evaluated the risk factors associated with p53 codon 72 polymorphism and gastric
      cancer carcinogenesis. METHODOLOGY: This study consisted of 51 patients and 59
      control subjects. We then evaluated the patient's age, sex, smoking and alcohol
      consumption habits, tumor location, cell differentiation, lymph node involvement,
      distant metastasis and tumor stage. Finally the p53 gene codon 72 polymorphism
      was analyzed by polymerase chain reaction (PCR). The results of polymorphic
      genotype were stratified with the above risk factors and the associations were
      analyzed. RESULTS: There was no significant difference between the polymorphic
      genotypes and the two study groups. However, when the genotypes were further
      stratified with co-factors, the results revealed a significant association with
      tumor location. The proline homozygote was more frequent in the patients with
      gastric cancer at the cardia than in those with cancer at the antral or corpus
      locations. (55.56% of cardia vs. 14.28% of corpus and antrum, p=0.024). The
      arginine allele was associated with antral and corpus location of gastric cancer
      and the proline allele was associated with cardial location (OR=3.25, p=0.026).
      Also, these polymorphisms do not seem to be associated with age, sex, smoking and
      alcohol consumption, cell differentiation, lymph node involvement, tumor stage
      and distant metastasis. CONCLUSIONS: The proline allele at p53 codon 72 is
      associated with adenocarcinoma of the gastric cardia, and the arginine allele is
      associated with cancer of the antral and corpus locations. These findings suggest
      that different genotypes of the p53 gene in different locations of stomach might
      implicate a different cause of tumor growth.

PMID- 15966239
TI  - The treatment of gastric fundal varices--endoscopic therapy versus interventional
      radiology.
AB  - BACKGROUND/AIMS: Balloon-occluded retrograde transvenous obliteration is an
      effective method for treating gastric fundal varices. The present retrospective
      study was performed to determine the clinical efficacy for gastric fundal varices
      associated with endoscopic therapy, surgery, and interventional radiology
      including balloon-occluded retrograde transvenous obliteration. METHODOLOGY: We
      classified 26 patients to a surgery group, an endoscopic therapy group, and an
      interventional radiology group according to initial treatment and subsequent
      treatment, and we compared the rates of hemostasis, eradication, and bleeding in
      these groups. RESULTS: Interventional radiology was successful in arresting acute
      hemorrhage in 100% of cases, while endoscopic therapy was successful in only 50%
      of cases. The rate of eradication was 100% in the Surgery group, 66.7% in the
      Endoscopic Therapy group, and 50% in the Interventional Radiology group. The
      cumulative bleeding rate at 5 years was 0% in the Surgery group, 0% in the
      Endoscopic therapy group, and 11.1% in the Interventional Radiology group. No
      significant difference was observed between the three groups. CONCLUSIONS: The
      treatment-of-choice for gastric fundal variceal hemorrhage is endoscopic
      injection sclerotherapy and ligation, with interventional radiology as the back
      up procedure in case endoscopic injection sclerotherapy and ligation is
      unsuccessful. Interventional radiology is the treatment-of-choice for elective
      treatment of gastric fundal varices.

PMID- 15966240
TI  - High en bloc resection rate achieved by endoscopic mucosal resection with IT
      knife for early gastric cancer.
AB  - BACKGROUND/AIMS: Circumferential endoscopic mucosal resection (EMR) around
      lesions performed by an insulation-tipped diathermic knife (IT knife) increases
      en bloc resection rates, suggesting the possibility of expanding indications for
      EMR. METHODOLOGY: Clinical outcome of EMR performed by IT knife under general
      anesthesia was evaluated for 26 patients with 29 early gastric cancer. RESULTS:
      Successful en bloc resection rates obtained by the IT knife were 100, 87.5, 90.0
      and 100% for lesions < or =10 mm in size, 11-20 mm, 21-30 mm, and > or =31 mm,
      respectively. They were significantly higher with the IT knife than those
      obtained by the conventional method (IT knife method: 93.1% vs. conventional
      method: 28.5%, p<0.0001). Two lesions were lateral margin positive, and in three
      cases invasion of lesions was observed as deep as the submucosa. Distal, total,
      and proximal gastrectomy with D2 lymphadenectomy, respectively, was provided in 3
      cases; however, no lymph node involvement was found in any of the resected
      specimens. Bleeding and perforation were observed in 3 cases, respectively,
      however, no additional surgical treatment was required for these patients.
      CONCLUSIONS: EMR by means of the IT knife under general anesthesia can be
      performed safely and adequately. It is a useful treatment modality for early
      gastric cancer.

PMID- 15966241
TI  - Telomerase activity as prognostic factor in gastrointestinal stromal tumors of
      the stomach.
AB  - BACKGROUND/AIMS: Although size and mitotic counts have been reliable predictors
      of clinical outcome, identification of gastrointestinal stromal tumor (GIST) of
      the stomach with a metastatic potential through hematoxylin and eosin staining is
      not always accurate. Telomerase activity, often detected in malignant tumors, may
      have a role as a marker for high-grade malignancy. METHODOLOGY: Immunostaining
      with antibodies against KIT protein, CD34, and other molecules that are relevant
      for evaluation of cell differentiation and proliferation was performed for 36
      primary gastric submucosal tumors to confirm the diagnosis of GIST. DNA was
      extracted from the surgically resected specimens of 24 of 36 patients, and c-kit
      mutation was analyzed by direct sequencing after PCR amplification of the exon
      11. Telomerase activity was quantitatively evaluated for all 36 patients using
      fluorescence-based telomeric amplification assay protocol (TRAP) analysis.
      RESULTS: c-kit mutation was observed in 58% of the patients evaluated. Telomerase
      activity was detected in 14 specimens (39%), but not in the specimens without c
      kit mutation. All 5 patients who suffered from metastatic or recurrent disease
      exhibited c-kit mutation and a high level of telomerase activity. CONCLUSIONS:
      Measurement of telomerase activity, along with c-kit mutation analysis, is useful
      for identifying GIST with a potential for malignant behavior.

PMID- 15966242
TI  - Prognostic and clinical evaluation of patients with T2 gastric cancer.
AB  - BACKGROUND/AIMS: Little is known about the clinicopathological features of
      intermediate-stage T2 gastric cancer, defined as tumors invading the muscularis
      propria or subserosa. METHODOLOGY: Of 808 patients with gastric cancer, 210
      patients (25.9%) who underwent gastrectomy for T2 gastric cancer were selected
      for this retrospective study. The clinicopathologic findings of these patients
      were analyzed retrospectively from their hospital records. RESULTS: Of all 808
      patients with gastric cancer, 73 patients (9.0%) had tumors invading the
      muscularis propria (mp). The remaining 137 patients (16.9%) had tumors invading
      the subserosa (ss). Compared with ss gastric cancer, mp gastric cancer was
      associated with smaller tumor size, an absence of lymphatic spreading, and
      hematogenous and late recurrence [disease-free interval: 654.5 days (mp) vs.
      365.5 days (ss)]. Univariate analysis of cases with curative operations showed
      that lymphatic invasion, and lymph node metastasis were significant prognostic
      factors in patients with T2 gastric cancer. Further examination by multivariate
      analysis demonstrated that pN2 or higher as classified by both the JCGC (Japanese
      Classification of Gastric Cancer) and the TNM lymph node staging systems was a
      predictor of poor prognosis. CONCLUSIONS: JCGC and TNM lymph node staging systems
      were the most reliable prognostic factors for T2 gastric cancer. Close follow-up
      should be required for patients with stage pN2 or higher gastric cancer. Long
      term follow-up should be required for mp cancers, in particular.

PMID- 15966243
TI  - Primary squamous cell carcinoma of the stomach: a case report with
      immunohistochemical and molecular biologic studies.
AB  - Primary squamous cell carcinoma (SCC) of the stomach is an extremely rare tumor
      and its pathogenesis is still unknown. We report a case of SCC of the stomach in
      a 69-year-old man. The patient's stomach contained an area of SCC surrounded by
      squamous metaplasia. To our knowledge, this is the first reported study to have
      investigated the pathogenesis of this tumor type by immunohistochemistry, liquid
      hybridization assay for human papilloma virus (HPV) infection, and polymerase
      chain reaction for Epstein-Barr virus (EBV) infection. These tests yielded proof
      of EBV infection in surgical specimens of the tumor. Therefore, we suggest that
      EBV infection may be involved in the pathogenesis of SCC arising in the stomach.

PMID- 15966244
TI  - Regression of EI2-stage low-grade gastric MALT-lymphoma after H. pylori
      eradication.
AB  - To our knowledge there are only a few reports showing a role of eradication
      therapy for H. pylori in the treatment of low-grade MALT-lymphoma, of stage EI2.
      We report a rare case of MALT-lymphoma, invading all of the gastric wall, which
      regressed after eradication of H. pylori. The regression was well documented by
      endoscopic ultrasonography (EUS). A 70-year-old man was referred to us for upper
      endoscopy that showed a single ulcer of 3cm in diameter at the gastric angulus.
      Histology, immunohistochemistry and PCR analyses diagnosed a low-grade MALT
      lymphoma in the presence of H. pylori infection. EUS showed a tumor invasion of
      all the gastric wall. The serosa layer, also, appeared irregular and interrupted
      in some points. The lymph nodes around the duodenum and the stomach were not
      involved. An anti-H. pylori therapy was started. After 1 year from the diagnosis,
      EUS showed the reappearance of the normal layers of the stomach. The patient is
      actually disease free. This result suggests that in EI2-stage gastric lymphoma of
      MALT type, in the absence of both high-grade malignancy foci and
      t(11;18)(q21;q21) chromosomal translocation, an eradication treatment may be
      considered as a first therapeutic option.

PMID- 15966246
TI  - No health without mental health.

PMID- 15966245
TI  - Successful downstaging by S-1-based chemotherapy followed by surgical resections
      for gastric carcinoma with extensive distant lymph node metastasis - report of
      two cases and a review of cases with surgical resection after downstaging by S-1
      based chemotherapy.
AB  - We report two cases of gastric carcinoma with successful downstaging using S-1
      based chemotherapy followed by surgical resection, which enabled us to confirm
      the histological effect of chemotherapy. These patients were associated with
      extensive distant lymph node metastases for which curative resections were
      unlikely to be performed. We performed anticancer chemotherapy using S-1 with or
      without concomitant administration of cisplatin in a neoadjuvant setting. After
      the successful downstaging of these metastatic gastric carcinomas evaluated by
      imaging analyses, the patients underwent surgical resections. Effect of the
      chemotherapy was confirmed by the histological analyses. These cases provide
      further evidence, suggesting that S-1-based chemotherapy enabled downstaging of
      stage IV gastric carcinoma associated with distant extensive lymph node
      metastasis and consequently the following possible curative resections. The
      review of 16 cases of S-1-based chemotherapy followed by surgical resections
      indicated that, although downstaging may not be expected when N3 lymph node
      metastases are evident, the S-1-based chemotherapeutic regimens were effective in
      short cycles for patients in whom potential curative resection is expected.
      Survival benefit of downstaging followed by surgical resection, however, remains
      to be further elucidated.

PMID- 15966247
TI  - The momentum for mental health promotion.

PMID- 15966248
TI  - Mental health promotion works: a review.

PMID- 15966249
TI  - Poverty, gender and mental health promotion in a global society.

PMID- 15966250
TI  - The implemention of mental health promotion programmes.

PMID- 15966251
TI  - I'm from the government and you want me to invest in mental health promotion.
      Well why should I?

PMID- 15966252
TI  - Mental health promotion in public health.

PMID- 15966253
TI  - What makes mental health promotion effective?

PMID- 15966254
TI  - Why "mental" health promotion?

PMID- 15966255
TI  - Confocal laser scanning microscopy in orthopaedic research.
AB  - Confocal laser scanning microscopy (CLSM) is a type of high-resolution
      fluorescence microscopy that overcomes the limitations of conventional widefield
      microscopy and facilitates the generation of high-resolution 3D images from
      relatively thick sections of tissue. As a comparatively non-destructive imaging
      technique, CLSM facilitates the in situ characterization of tissue
      microstructure. Images generated by CLSM have been utilized for the study of
      articular cartilage, bone, muscle, tendon, ligament and menisci by the foremost
      research groups in the field of orthopaedics including those teams headed by
      Bush, Errington, Guilak, Hall, Hunziker, Knight, Mow, Poole, Ratcliffe and White.
      Recent evolutions in techniques and technologies have facilitated a relatively
      widespread adoption of this imaging modality, with increased "user friendliness"
      and flexibility. Applications of CLSM also exist in the rapidly advancing field
      of orthopaedic implants and in the investigation of joint lubrication.

PMID- 15966256
TI  - [Alpine medicine--a stay at middle altitude].

PMID- 15966257
TI  - [Cardiorespiratory and metabolic responses during mountain hiking and downhill
      skiing].
AB  - In Austria, more than 10 million hikers and skiers annually visit moderate
      altitudes. Nevertheless, there is little information on the frequency of
      cardiovascular diseases in mountaineers and the exercise responses during
      physical activity in the mountains. The prevalence of cardiovascular diseases was
      determined by an inquiry of 527 mountain hikers and 785 alpine skiers. Two groups
      (n = 35) performed step tests at low altitude (600 m) and at high altitude (2000
      m and 3500 m). Exercise responses to hiking and skiing were recorded in the
      subjects of the third group (n = 10). Hiking and skiing at moderate intensity
      evoked moderate cardiovascular and metabolic responses which are also well
      tolerated by persons with non-severe cardiovascular and respiratory diseases. Low
      fitness, increasing altitude and intensity increased exercise responses, thereby
      enhancing the probability of cardiovascular events. A high degree of fitness
      based on regular training decreases exercise responses and improves exercise
      tolerance.

PMID- 15966258
TI  - Oxidative stress caused by acute and chronic exposition to altitude.
AB  - In this article, current views on cellular and molecular biology (biochemical)
      mechanisms are discussed under the aspect of altitude exposition. The Andean,
      Tibetan, and Ethiopian patterns of adaptation to high-altitude hypoxia are known
      [Beal et al. (2002) Proc Natl Acad Sci USA 99: 17215-17218]. The phylogenetic
      tree of the human species suggests that there are genetic differences in
      adaptation patterns to chronic hypoxic hypoxia. Five defense mechanisms are well
      established for lowlanders who are exposed to acute hypoxic hypoxia. Consequences
      of the cellular decrease in ATP are the formation of hypoxanthine and xanthine,
      which are the substrates for the massive formation of superoxide anion radicals
      and hydrogen peroxide via the oxidase activity of the xanthine oxidoreductase
      reaction. Under severe hypoxia, about 51 % of the total inhaled oxygen is used to
      form superoxide anion radicals in rat liver [Gerber et al. (1989) Adv Exp Med
      Biol 253B, Plenum Press, New York, 497-504]. The reactivity and selectivity of
      the superoxide anion radical are modified by specific interactions and electron
      exchange. It is commonly accepted that the superoxide anion radical in aqueous
      solutions has a lifetime in the millisecond range. However, electron spin
      resonance spectroscopy studies in a KO2/H2O/iron ion system revealed for the
      first time a stabilization of a part of the initially added superoxide anion
      radicals lasting up to hours at room temperature [Foldes-Papp (1992) Gen Physiol
      Biophys 11: 3-38]. Superoxide anion radicals adsorbed on an oxidic iron hydrate
      phase in aqueous systems might function as a strong oxidant similar to that
      species which has been suggested to be a complex between oxygen and different
      valence states of iron in the initiation of lipid peroxidation by ferrous iron.
      There were serious doubts about the identity of alkoxy radicals. For the first
      time, alkoxy radicals were directly demonstrated in solution by electron spin
      resonance spectroscopy [Foldes-Papp et al. (1991) Adv Synth Catal 333: 293-301].
      The redox status in mammalian cells is mainly determined by the antioxidant
      glutathione, which is a key player in maintaining the intracellular redox
      equilibrium and in the metabolic regulation of the cellular defense against
      oxidative stress. As reactive oxygen species occupy an essential role in membrane
      damage, the idea of membrane-bound enzymatic defense mechanisms gets a new
      dimension [Foldes-Papp et al. (1981) Acta Biol Med Ger 40: 1129-1132; Foldes-Papp
      and Maretzki (1982) Acta Biol Med Ger 41: 1003-1008]. The steady-state between
      antioxidants and pro-oxidants affects the gene expression via hypoxia-induced
      transcription activities. The transcription factor hypoxia-inducible factor 1
      (HIF-1) is a global regulator of oxygen homeostasis. As discussed in this
      article, hypoxia or 'oxidative stress' is accompanied by appropriate molecular
      adaptation mechanisms at the enzymatic or epigenetic level (enzymatic and non
      enzymatic radical inhibitors, posttranslational modifications) and at the genetic
      level (transcription, translation).

PMID- 15966259
TI  - Effects of cable car ascent to 2700 meters on mean EEG frequency and event
      related desynchronization (ERD).
AB  - In the Eastern Alps, the Dachstein massif with a height of almost 3000 m is an
      ideal location for investigating the effects of changes in altitude on the human
      body. A cable car allows an ascent within a few minutes to 2700 m, where the
      partial pressure of oxygen is about 550 mm of mercury compared to 760 mm at sea
      level. Ten healthy subjects performed a reaction time task at an altitude of 990
      m and 2700 m. The subjects were instructed to perform a right hand index finger
      movement as fast as possible after a green light had flashed. The green light
      flashed 50 times. Simultaneously to the task, the electroencephalogram (EEG) was
      recorded. The event-related desynchronization (ERD) analysis of the EEG data
      showed that changes in alpha ERD values are not significant, but event-related
      synchronization (ERS) values in the beta band decrease significantly from around
      50 % to 10 %. Furthermore, the mean frequency of the beta band increased from
      16.68 Hz to 16.81 Hz (p = 0.0019) with the ascent. The suppressed post-movement
      beta ERS at an altitude of 2700 m may therefore be interpreted as a result of an
      increased cortical excitability level when compared with the reference altitude
      of 990 m above sea level.

PMID- 15966260
TI  - [Aspects and necessity of moderate-altitude research].
AB  - Alpinism in all its variations is a leading factor in tourism. Within a few
      decades, alpine sports, even at high altitudes, have become available to a wide
      range of people. Now, more people than ever before are hiking, trekking, climbing
      and skiing at moderate and high altitudes. Annually, 40 million people spend time
      in the Alps and 100 million visit high altitudes worldwide. However, alpine
      excursions may entail health problems and many aspects of impaired adaptation to
      altitude remain unstudied. High-altitude research has mainly been associated with
      expeditions, with moderate altitudes receiving far less attention, though most
      tourism takes place at that level. The overwhelming numbers of alpine tourists
      mean that there is urgent need for high- and moderate-altitude medical research,
      which would also be within the realm of political responsibility in mountainous
      countries. Research in mountain medicine and dissemination of relevant findings
      can show how to improve and conserve performance in healthy individuals and could
      point the way toward new, safe approaches in the rehabilitation of patients with
      chronic diseases. It is imperative that mountain medicine continues to develop on
      a scientific basis.

PMID- 15966261
TI  - [Interaction of hypoxia and haemostasis--hypoxia as a prothrombotic factor at
      high altitude?].
AB  - For an extended period of time various research projects have been conducted on
      the relationship of hypoxia and haemostasis. The enclosed article contains the
      conclusion to which extent lack of oxygen can activate the coagulation system and
      induce a prothrombotic state. The majority of studies proved a shortening of
      coagulation times during acute exposure to hypoxia, whereas activated parameters
      of coagulation and fibrinolysis like prothrombin fragment F1+2 as well as
      thrombin-antithrombin III complexes and D-dimer remained mostly unmodified. It is
      suggested that a prolonged sojourn at high altitudes could lead to activation of
      the coagulation system through an increase of haematocrit and blood viscosity.
      Recently it was proven that people living at high altitudes show an enhanced risk
      of stroke incidents. The significance of the change in haemostasis on that
      outcome has not yet been part of the research. However, it has been proven that
      the activity of the coagulation system does not play a pathophysiological part in
      the development of acute mountain sickness and high altitude pulmonary edema.
      Recent studies also demonstrated that moderate hypoxia during long haul flights
      may not be the main trigger in inducing deep vein thrombosis in passengers.

PMID- 15966262
TI  - [Non-traumatic aspects of sport climbing].
AB  - Within only two decades, sport climbing has developed into an activity performed
      by a large group of the active population in every (western) country, with nearly
      all ages being represented. The difficulties now overcome by most athletes are in
      advance of those expected 20 years ago. Nevertheless, publications, which focus
      on sport climbing undertaken by those with chronic diseases like hypertension or
      coronary heart disease, are rare. The actual paper defines the criteria that must
      be fulfilled for safe sport climbing, and gives advice on preventive medical
      care.

PMID- 15966263
TI  - [The effects of chronic hypobaric conditions: skeletal, muscular, and other
      phenotypic characteristics in high altitude dwellers].
AB  - Many studies have concentrated on investigating the effects of short and medium
      term hypobaric conditions in people living at low altitudes. In contrast, only
      little is known about long term or genetic adaptations to chronic hypobaric
      conditions in people living at high altitudes. A small number of phenotypic
      characteristics have been defined in these people so far, comprising hormonal
      functions, oxygen saturation of hemoglobin, skeletal growth, muscular morphology
      and function, cardiovascular functions, and fluid and electrolyte changes.
      Several of these characteristics have been attributed to genetic adaptations.
      However, so far, no specific genes coding for any of the specific phenotypes
      found in high altitude dwellers have been detected.

PMID- 15966264
TI  - [Concept for a bioclimatic evaluation of an expedition and trekking area at
      moderate and high altitudes].
AB  - This paper presents a concept which is built up on climate data with a long
      period of observation (temperature, wind conditions, precipitation, irradiation,
      and the frequency of low pressure weather situations with unfavorable biotropy
      stages). It therefore allows an evaluation of the bioclimate of a high mountain
      area. With the help of this relatively simple method, the risk of problems like
      AMS can be better estimated. Latest comparisons between different agencies of
      expeditions show that often the time schedule for climbing to the summit is too
      short and allows too little time for acclimatization; furthermore the number of
      days allowed for recreation is too small. A comparison of selected alpine regions
      shows better conditions in, for example, the Mount Kenia/Kilimandjaro region and
      parts of the western Andes in Chile, whereas the Himalaya and the Karakorum group
      can be problematic.

PMID- 15966266
TI  - [Performance testing in mountaineering].
AB  - Laboratory ergometry to exhaustion allows cardiopulmonal risk assessment for the
      prevention of health problems related to mountaineering. Moreover, exercise
      testing evaluates functional status, so permitting individualized training
      programs and evaluation of training effects. Additionally, mountaineering
      specific performance diagnosis allows individual as well as group-specific
      determination of exercise performance related to field conditions. Laboratory
      tests are standardized, easy to perform and cost effective. Treadmill ergometry
      with constant walking speed and increasing inclination is suggested to be
      predictive for mountaineering performance. On the other hand, the validity for
      the specific conditions for mountaineering is questionable. Standardized
      laboratory exercise tests combined with sport-specific exercise tests provide
      rough information on the ability to sustain real-situation strain. To compare
      individual exercise performance, published data tables obtained from field tests
      may be used. It must, however, be mentioned that high-altitude-adaptation is
      independent of exercise performance evaluated separately.

PMID- 15966265
TI  - [The possible role of adrenomedullin in adaption to high altitude].
AB  - Diuresis and natriuresis are well-known responses to acute hypoxic exposure. Even
      though there have been many studies on the hormonal regulation of the hypoxic
      diuretic response (HDR), most of the fluid-regulating hormones showed no
      consistent correlation to HDR. The pathophysiology of high altitude related
      syndromes was often seen to be linked to an impairment of volume regulating
      processes. Adrenomedullin (AM) is a recently discovered polypeptide with
      diuretic, natriuretic and vasodilatory properties whose production is basically
      mediated by hypoxia. As yet, little is known about the action of AM under hypoxic
      conditions in vivo. We present evidence that AM may play a role in the physiology
      and pathophysiology of human adaption to high altitude.

PMID- 15966267
TI  - [Treatment of freezing injury].
AB  - Report on therapeutic procedures in patients with second and third degree
      congelations (frostbite) on the feet. Two mechanisms of tissue damage caused by
      exposure to cold temperature will be discussed pathophysiologically: direct
      freezing injuries and cell death through intra and extracellular ice crystal
      formation as well as transient and finally irreversible tissue damage due to
      decreased perfusion. The condition of decreased perfusion results from persistent
      vaso-constriction induced by cold temperature, increased blood viscosity, sludge
      phenomenon and occlusion by platelet thrombi in the microvasculature. Frostbite
      beyond the erythematous stage should be treated primarily with a parenteral
      therapy in order to improve the hemorrheologic parameters, in particular within
      the micro-vascular compartment. Colloidal plasma volume expander such as 10%
      dextran solution is used to increase the intravascular volume. This solution
      (with its coating effect) and pentoxifyllin lowers the aggregation of
      erythrocytes and platelets. The latter will also be favourably influenced by the
      use of iloprost or acetylsalicylic acid. Iloprost as a stable metabolite of
      prostacyclin is a powerful vasodilator which attenuates the peripheral vascular
      resistance and activates fribrinolysis. Pentoxifyllin is considered to lower
      pathologically increased levels of fibrinogen. Both drugs may protect against
      damage of the vascular endothelium. Based on their pharmacological effects the
      above-mentioned drugs may improve tissue perfusion and therefore tissue damage
      caused by frostbite can be limited. However, an important factor is to strictly
      avoid bacterial infections in the cold-damaged tissue.

PMID- 15966268
TI  - The International Classification of Headache Disorders, 2nd edition: application
      to practice.
AB  - The International Classification of Headache Disorders, second edition (ICHD-II)
      was the result of 4 years' work by a large number of headache experts from
      different parts of the world. This article summarizes the main new features of
      ICHD-II, compared with the original International Headache Society
      classification: better definition of migraine with aura, inclusion of chronic
      migraine, inclusion of a number of new primary headaches (SUNCT, hypnic headache,
      benign thunderclap headache, new daily-persistent headache, hemicrania continua),
      better definition of the secondary headaches, introduction of medication-overuse
      headache and of headache attributed to psychiatric disorder. An appendix defines
      a number of entities for research purposes. The new classification has already
      been translated into many of the world's major languages and many more are in the
      pipeline. It is enormously important that headache experts support and encourage
      the use of the new classification in order to develop a common knowledge base,
      and that they research ways of further improving it.

PMID- 15966269
TI  - Comparing gray matter loss profiles between dementia with Lewy bodies and
      Alzheimer's disease.

PMID- 15966270
TI  - Neuropsychological tests and functional nuclear neuroimaging provide evidence of
      subclinical impairment in Nasu-Hakola disease heterozygotes.
AB  - Nasu-Hakola disease is a rare, recessively inherited disease characterized by
      presenile dementia and bone cysts. Until now, no evidence of subclincal
      pathological changes in individuals heterozygous for the mutations underlying
      Nasu-Hakola disease has been reported. We performed a functional neuroimaging
      (99mTc-ECD SPECT) and neuropsychological study of healthy members of an Italian
      family carrying a mutation in the TREM2 gene. Two healthy subjects heterozygous
      for one mutated TREM2 allele showed a deficit of visuospatial memory associated
      with hypoperfusion in the basal ganglia, whereas the homozygotes for the wild
      type allele of TREM2 did not show any abnormalities.

PMID- 15966271
TI  - Italian validation of the Royal Free Interview for Religious and Spiritual
      Beliefs.
AB  - Interest in the relevance of religion and spirituality to medicine is growing and
      concerns the possible association between religiousness, spirituality and well
      being. In the rehabilitation field these factors may affect outcome. We
      translated the "Royal Free Interview for Religious and Spiritual Beliefs" into
      Italian and validated the Italian language version. The translation the Royal
      Free Interview was accomplished in several steps. Certain adaptations were
      necessary in order to take into account certain peculiarities of the Italian
      language and of the Italian-speaking world. The Italian translation presented in
      this study shows internal consistency: Cronbach's alpha coefficient 0.82
      (spiritual scale) and 0.80 (philosophical scale) in the 53 healthy volunteers;
      alpha coefficient 0.79 (spiritual scale) and 0.64 (philosophical scale) in the
      stroke patients. Test-retest reliability, evaluated by means of the intraclass
      correlation coefficient, was 0.83 (spiritual scale) and 0.99 (philosophical
      scale). There are two main reasons why an Italian translation of a religious
      coping scale was deemed necessary: i) there is a growing awareness of the
      possible impact of faith on stress and on the outcome of many disabling diseases;
      ii) Italy has a large and aging population and thus a high prevalence of disabled
      patients.

PMID- 15966272
TI  - Hypnic headache responsive to indomethacin: second Italian case.
AB  - We report a case of hypnic headache (HH) fulfilling the criteria proposed by the
      revised IHS headache classification and rapidly responsive to indomethacin. The
      patient is a 70-year-old housewife who presented with a 7-year history of
      strictly nocturnal headache attacks. The headache occurred every night with a
      frequency of 1 to 2 attacks occurring between 03.00 and 04.00 a.m. Indomethacin
      was prescribed at a daily dose of 150 mg/day for 30 days and tapered down in 15
      days. Pain did not occur thereafter and at follow up, nine months after
      discontinuation of the drug, the patient was still pain-free with no relapses.
      This is the second Italian HH patient responsive to indomethacin, indicating that
      indomethacin may be a useful alternative treatment in HH patients, and providing
      further evidence in favour of a common pathophysiological mechanism in HH and
      other indomethacin-responsive primary headaches.

PMID- 15966273
TI  - Guidelines for the organization of headache education in Europe: the headache
      school.
AB  - According to its mission statement, one of the goals of the European Headache
      Federation (EHF) is to "educate Europe" about headache through the teaching of
      the key health personnel, such as young physicians and all those involved in
      headache management, about the seriousness of headache disorders. The countries
      of Europe share a close geographical proximity that facilitates international
      exchanges, particularly between university faculties. In recent years, this has,
      indeed, been the working basis of European educational endeavours in the field of
      headache. For a number of years, annual summer schools were organized in
      different European countries and a permanent Summer Headache School was set up in
      Cambridge (to be held every alternate year). The last summer headache school was
      held in Vilnius in 2002. In the past decade, a patronage scheme was also set up,
      which, combining two or more countries (one developed, one or more developing),
      allowed international exchanges of doctors and students for training purposes. In
      some centres, participants were also able to gain clinical practice and research
      experience by staying at the host institutions for extended periods of time. As a
      result of all this activity there have emerged, in Europe, "clusters" of people
      with a particular interest in headache. However, the rapid growth of insight into
      headache (new molecules, new headache categories, etc.) has contributed to a
      widening of the scientific gap between developing and developed countries.
      Moreover, in the past four years, due to the relative restriction of
      national/international drug company budgets, it has proved possible to organize
      only relatively inexpensive teaching courses. As a result, countries whose
      medical communities had been developing a "headache culture" now find themselves
      destined to be increasingly held back. Therefore, the EHF, in order to promote
      education on headache in Europe at national level, felt there was a need for
      guidelines for the organization of educational courses that meet uniform
      standards of excellence and in terms of code of conduct: guaranteed courses that
      will attract investors and those seeking to increase their knowledge, skills and
      understanding in the area of primary and secondary headache. The guidelines,
      presented here, specify the ideal length of a headache course, the number of
      lectures it should include, as well as the ideal number of participants and
      teachers. A sample course outline is provided, together with a checklist to help
      the organizers to meet the criteria for an EHF-approved headache school.

PMID- 15966274
TI  - Key developments in dermatology.

PMID- 15966275
TI  - The GP's role in urticaria.

PMID- 15966276
TI  - Recognition and management of cutaneous photosensitivity.

PMID- 15966277
TI  - Skin signs of internal disease.

PMID- 15966278
TI  - Casebook: psoriasis.

PMID- 15966279
TI  - Managing UTIs in children.

PMID- 15966280
TI  - Advances in cardiovascular medicine.

PMID- 15966282
TI  - On decoy cells.

PMID- 15966283
TI  - Periodic assessment of urine and serum by cytology and molecular biology as a
      diagnostic tool for BK virus nephropathy in renal transplant patients.
AB  - OBJECTIVE: To investigate the significance of polyomavirus (PV) viruria and
      viremia by morphologic, immunohistochemical and molecular analysis (multiplex
      nested-polymerase chain reaction) in renal transplant patients. STUDY DESIGN:
      Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant
      patients (n=106) were studied. RESULTS: Decoy cells were found in 53 samples
      (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and
      disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA
      (n=13). BKV was the prevailing genotype in patients with a high frequency of
      decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p =
      0.01) and BKV with a high number of decoy cells (p=0.003). PV DNA was amplified
      from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On
      24 renal biopsies (18 from the decoy cell-negative and 6 from the decoy cell
      positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4
      biopsies, all from the group with a high frequency of decoy cell excretion. PVN
      was not identified in renal biopsies from the decoy cell-negative group.
      CONCLUSION: PV infection is frequent in renal transplant patients. The BKV
      genotype in urine and serum is significantly related to a high frequency and high
      number of decoy cells. PVN occurs only in patients with BKV viremia and a high
      number and frequency of decoy cell excretion in urine. In the absence of decoy
      cells, PVN can be excluded. Cytologic analysis of urine is an important
      diagnostic tool for screening renal transplant patients at risk of PVN.

PMID- 15966284
TI  - Quality assurance in cervical smears: 100% rapid rescreening vs. 10% random
      rescreening.
AB  - OBJECTIVE: To compare 100% rapid rescreening of cervical smears with 10% random
      rescreening as a method of quality assurance. STUDY DESIGN: A total of 5215
      smears, randomly selected from smears reported as negative by cytotechnologists
      during routine screening, underwent 100% rapid rescreening by senior
      cytotechnologists. Ten percent of these smears, selected at random, were
      rescreened by other senior cytotechnologists. The gold standard was defined by
      cytopathologists, who rescreened all 5215 smears. After excluding unsatisfactory
      smears detected by cytopathologists, 4271 were included in the analysis. RESULTS:
      The 100% rapid rescreening method identified 69.9%, 95.7% and 100%, respectively,
      of atypical squamous cells of undetermined significance, low grade squamous
      intraepithelial lesion and high grade squamous intraepithelial lesion cases
      reported by the cytopathologists. The 100% rapid rescreening method showed a
      sensitivity of 73.5% and specificity of 98.6%. The 10% rescreening method showed
      sensitivity of 40.9% and specificity of 98.8%. CONCLUSION: One hundred percent
      rapid rescreening is an efficient method of internal quality assurance in
      cervical smear diagnosis. It can reduce the false negative rate and therefore can
      provide greater certainty to women who have received negative results. Well
      trained cytotechnologists are able to identify abnormal smears in 1-minute rapid
      rescreening.

PMID- 15966285
TI  - Pap smear quality parameters of 3 sampling devices used by auxiliary nurse
      midwives on symptomatic rural Indian women.
AB  - OBJECTIVE: To determine whether auxiliary nurse midwives (ANMs) could make good
      quality Pap smears after focused training and to determine which sampling device
      is most effective in their hands in field practice areas. STUDY DESIGN: In a
      downstaging cervical cancer screening program, 394 symptomatic rural Indian women
      between the ages of 35 and 60 were identified by the ANMs in 2 villages, with a
      total population of 14,747, and were invited to have a smear taken. Two hundred
      of these symptomatic women responded. The ANMs were educated to render
      information on screening for cervical cancer and to take smears with 3 sampling
      devices--Ayre spatula, modified spatula (with extended tip) and Cytobrush
      (Medscand AB, Malmo, Sweden). The smears were evaluated for 6 adequacy
      parameters. Smears made by gynecologists were used as controls. To establish the
      superiority of a method, chi2 tests were used. RESULTS: All smears made by the
      ANMs could be used to render a cytologic diagnosis. The adequacy parameters of
      all the smears made by ANMs at least matched those of the gynecologists. The best
      results were obtained with modified spatula (with extended tip) and combination
      of Cytobrush with modified spatula. CONCLUSION: Since only 50% of symptomatic
      rural women came for Pap testing, we conclude it is not easy to motivate women
      for such testing, even if a large-scale educational effort is made. ANMs can be
      taught to take reasonably good qualisuperior sampling device for ANMs is ty Pap
      smears. The superior sampling device for ANMs is the modified spatula (with
      extended tip).

PMID- 15966286
TI  - Cytologic findings in pap smears with Actinomyces-like organisms.
AB  - OBJECTIVE: To detect whether there is a relationship between the presence
      ofActinomyces-like organisms (ALOs) and cytologic findings. STUDY DESIGN:
      Papanicolaou-stained smears from 2290 women were examined cytologically. Nineteen
      (0.83%) of the 2290 were diagnosed with ALOs and became the study group. Patients
      without infectious agents (n=1792) were the control group. Statistical analyses
      were conducted with the chi2 test using the SPSS program (Chicago, Illinois,
      U.S.A.). RESULTS: The study and control groups were compared statistically. There
      was a significant correlation between the presence of ALOs and other cytologic
      findings, such as Trichomonas vaginalis, cocci, pseudoeosinophilia, endocervical
      cells, superficial cells, lactobacilli and polymorphonuclear leukocytes (p <
      0.05), but there was no statistically significant difference between the presence
      of ALOs and metaplastic cells, parabasal cells or nuclear changes (p > 0. 05).
      CONCLUSION: ALOs in cervicovaginal smears might provide a milieu for growing some
      infectious agents, such as Trichomonas vaginalis and cocci. Lactobacilli were
      less plentiful in these cases. Vaginal discharge and abdominal pain were also
      important clinicalfindings for the detection ofALOs. Another finding was long
      term usage of intrauterine contraceptive devices, which can cause the overgrowth
      of ALOs in vaginal mucosa.

PMID- 15966287
TI  - Collagen balls in cervica-vaginal smears.
AB  - OBJECTIVE: To dewribe the recent detection of collagen balls in cervical-vaginal
      specimens from 7 women within the previous 2 years. STUDY DESIGN: Papaniolaou
      stained cervical-vaginal specimens, 3 conventional and 4 ThinPreps (Cytyc Corp.,
      Boxborgugh, Massachusetts, U.S.A.), were reviewed due to the presence of
      structures indistinguishable from collagen balls. RESULTS: The structures
      displayed 3-dimensionality, a hyalinized core and a covering of benign-appearing
      cells,fratures identical to those seen in collagen balls from serous cavity
      fluids. Averaging 94 x 60 microm, they were similar in size to a human oocyte at
      ovulation. Their presence did not correlate with any concurrent Pap smear
      findings or previous medical history. CONCLUSION: Since collagen balls have
      previously been reported to occur only in serous cavity fluids, they are thought
      to arise at those locations. We propose that collagen balls are transported via
      the fallopian tube and uterine fundus to the cervix, much in the same way that an
      ovum is transported to the uterine flindus for implantation. The likelihood of
      such an event is most probably quite low. The recent finding of 7 cases of
      collagen balls may correlate with an increased prevalence of collagen balls in
      peritonealfl uids, thus increasing the probability of their transport to the
      cervix.

PMID- 15966288
TI  - Assessment of micronucleus frequency in normal oral mucosa of patients exposed to
      carcinogens.
AB  - OBJECTIVE: To assess the presence of micronuclei in exfoliated oral mucosal cells
      collected from 3 anatomic sites in patients exposed to tobacco and alcohol. STUDY
      DESIGN: Smears were prepared with normal oral mucosal cells obtained from the
      lower lip, tongue border and floor of the mouth of 21 controls, 28 tobacco users
      and 19 tobacco/alcohol users. Slides were stained with Feulgen stain for
      quantification of micronucleated cells, karyorrhexis and "broken eggs." RESULTS:
      The groups were similar in terms of the mean number of micronucleated cells and
      cells undergoing karyorrhexis. In the comparison of anatomic sites, the mean
      number of cells undergoing karyorrhexis was higher on the lower lip than on the
      tongue border or floor of the mouth (all groups). A significantly higher number
      of broken eggs was observed in the control group when compared to the tobacco and
      tobacco/alcohol groups at all anatomic sites. CONCLUSION: The higher number of
      broken eggs in patients not exposed to tobacco and/or alcohol suggests that this
      nuclear alteration may be associated with DNA repair or a healthy mucosa. A trend
      toward an increased number of micronucleated cells was observed for tobacco
      and/or alcohol users at all anatomic sites.

PMID- 15966289
TI  - Frequency of trichomonads as coinfecting agents in Pneumocystis pneumonia.
AB  - OBJECTIVE: To investigate the incidence of the association of Trichomonas and
      Pneumocystis in the lung. STUDY DESIGN: Sixty-six bronchoalveolar lavage fluid
      (BALF) samples from immunocompromised patients with pneumocystosis were
      retrospectively examined microscopically. RESULTS: Trichomonads were found as
      coinfecting agents in 60% of BALF samples. The frequency and abundance of
      trichomonads was increased, up to 100%, in cases rich in Pneumocystis.
      CONCLUSION: The data suggest that pulmonary Trichomonas infection occurs
      frequently in the course of Pneumocystis pneumonia. The role of trichomonads in
      causing alveolar damage during Pneumocystis pneumonia is hypothetical.

PMID- 15966290
TI  - Fine needle aspiration of borderline ovarian lesions. Is It useful?
AB  - Borderline ovarian tumors are a low grade form of epithelial ovarian carcinoma
      with a low rate of growth and a low potential to invade or metastasize. According
      to the new World Health Organization classification, these tumors are placed
      between clearly benign and obviously malignant tumors because they exhibit some,
      but not all, of the morphologic features of malignancy. For a distinction between
      borderline lesions and cystadenomas or carcinomas, 2 criteria are of the utmost
      importance: presence of nuclear atypia and absence of stromal invasion. The
      pathologic subtype ofperitoneal implants is probably one of the main
      prognosticfactors in patients with serous tumors of low malignant potential,
      while the prognostic value of micropapillary serous carcinoma in patients with
      noninvasive implants remains debatable. Although fine needle aspiration (FNA) is
      the most accurate diagnostic method in cytopathology, its value in the diagnosis
      of borderline lesions is limited, mainly because of its inability to establish
      the absence of stromal invasion. The diagnostic accuracy of RNA can be improved
      by supplementing cytologic examination with such diagnostic techniques as
      immunocytochemistry and cytometry.

PMID- 15966291
TI  - Fine needle aspiration of lymphadenopathy in visceral leishmaniasis.
AB  - OBJECTIVE: To illustrate the cytomorphologic features of Leishmania lymphadenitis
      associated with visceral leishmaniasis (V/L) and post-kala-azar dermal
      leishmaniasis (PKDL) and to highlight the fact that Leishmania lymphadenitis must
      he included in the differential diagnosis of patients presenting with
      lymphadenopathy, particularly in areas endemic for the disease. STUDY DESIGN:
      Fine needle aspiration (FNA) was routinely done in 21 cases of lymphadenopathy in
      VL (18 cases) and PKDL (3 cases), and the detailed cytomorphologic features were
      correlated with the respective histopathologic findings. RESULTS: Amastigote
      forms of Leishman-Donovan (LD) bodies were seen in 19 cases both intracellularly,
      in histiocytes and multinucleate giant cells, and extracellularly. The FNA smears
      revealed a polymorphous population of cells composed of lymphocytes, histiocytes,
      plasma cells, giant cells and tingible body macrophages. In a few cases,
      epithelioid cell granulomas were also seen. The cytomorphologic features were
      confirmed and correlated on histopathology. CONCLUSION: Not all lymphadenopathy
      in VL and PKDL is due to Leishmania lymphadenitis. Demonstration of LD bodies on
      FNA smears helps with the early diagnosis of VL and PKDL with lymphadenopathy
      where the diseases are endemic.

PMID- 15966292
TI  - Improving recognition of thyroid carcinoma in rapid-consultation specimens.
AB  - OBJECTIVE: To improve recognition of thyroid carcinoma in rapid consultation on
      Diff-Quik-stained (Fisher Diagnostics, Middletown, Virginia, USA.) fine-needle
      aspiration (FNA) and rapid hematoxylin-eosin (H-E)-stained intraoperative scrape
      preparation (ISP) specimens by assessing 3 variables (anisokaryosis, nuclear
      overlap [NO] and scant/absent colloid) in cases of cellular follicular lesions
      (CFL), an indeterminate diagnostic category. STUDY DESIGN: Thirty-seven FNAs and
      28 ISPs diagnosed as CFL, with histologic follow-up, were evaluated in blinded
      fashion by 3 cytopathologists assessing the 3 variables. RESULTS: Over 90% of the
      malignant cases showed NO in both FNA and ISP, while only 22% of the benign cases
      did; positive and negative predictive values (PPV and NPV) were 82% and 100%. All
      malignant cases showed significant anisokaryosis in both FNA and ISP in contrast
      to 24% of benign cases; PPV and NPV were 74% and 100%. Scant/absent colloid was
      seen in 87% and 39% of malignancies in FNA and ISP, respectively, as compared to
      55% and 20% of the benign cases. PPV and NPV were 52% and 83% in FNA and 63% and
      60% in ISP, respectively. CONCLUSION: Application of these variables improves
      recognition of thyroid carcinoma, particularly in fine needle aspirates, while
      additional material may be requested. With ISP, their absence supports
      recommending against further surgery. Together, optimal surgical planning and
      outcome may be obtained.

PMID- 15966293
TI  - Fine needle aspiration biopsy with adjunct immunohistochemistry in intraocular
      tumor management.
AB  - OBJECTIVE: To assess the effectiveness of fine needle aspiration biopsy (FNAB),
      with and without immunohistochemistry (IHC), in the management of solid
      intraocular tumors. STUDY DESIGN: Thirty-three consecutive adults undergoing FNAB
      of suspected intraocular tumors were studied. Clinical, cytologic and histologic
      diagnoses were correlated. The positive predictive value, sensitivity and
      specificity of FNAB for detecting malignancy, the effect of lHC on the final
      cytologic diagnosis and the number of patients in whom clinical management was
      altered as a result of cytologic evaluation were determined. RESULTS: The
      positive predictive value was 96% with and 93% without adjunct IHC. The
      sensitivity and specificity of FNAB for detecting malignancy were 96% and 83%,
      respectively, with IHC. Without IHC, the sensitivity was unaltered, but the
      specificity was 67%. IHC confirmed the morphologic diagnosis in 75% of cases,
      made a diagnosis in 12.5% and changed a malignant diagnosis from carcinoma to
      melanoma in 6% of cases. The planned management was changed by the FNAB findings
      in 24% of patients. In 3 patients (9%), IHC was essential for diagnosis and
      management. No patients exhibited local tumor dissemination or recurrence
      associated with the biopsy. CONCLUSION: FNAB is a safe, sensitive and specific
      method of establishing a tissue diagnosis in a subset of patients with solid
      intraocular tumors. The routine use of immunohistochemical stain ing increases
      the diagnostic utility of the technique and may change clinical management.

PMID- 15966294
TI  - Solitary fibrous tumor: report of a case with an unusual presentation as a
      spindle cell parotid neoplasm.
AB  - BACKGROUND: Initially described as a pleural tumor, solitaryfibrous tumor of the
      parotid gland (SFT) is rare and has been reported at a wide range ofanatomic
      sites. Although cases of SFT arising in the parotid gland have been previously
      described, a review of the literature failed to reveal cytology-based reports of
      this entity. CASE: A 42-year-old man presented with a right parotid mass that had
      gradually enlarged over 3 years. He was otherwise asymptomatic. Fine needle
      aspiration biopsy of the mass showed a hypercellular smear composed of spindle
      cells in both clusters and isolated forms, with ovoid nuclei, evenly distributed
      chromatin, inconspicuous nucleoli and scant to moderate cytoplasm with focally
      wispy, collagenous, intercellular material. The background was hemorrhagic,
      without chondromyxoid matrix or inflammatory cells. There was no evidence of a
      myoepithelial component. A diagnosis of spindle cell neoplasm was rendered.
      Histologic examination of the total parotidectomy specimen revealed a SFT arising
      in the parotid gland. The diagnosis was supported by immunohistochemical studies.
      CONCLUSION: SFT is a well-circumscribed neoplasm composed of short, spindled,
      plump cells with scanty cytoplasm growing in a haphazard or "patternless"
      pattern. Tumor cells are intimately admixed with collagenous stroma.
      Hemangiopericytomalike vessels are frequently seen. Although SFT rarely occurs in
      the salivary gland and a definitive diagnosis based on cytologic preparations
      alone is difficult, the diagnosis of SFT can be considered when cytologic
      examination reveals a hypercellular smear composed of isolated, cohesive clusters
      of spindled, fibroblastlike cells associated with a collagenous component in
      ahemorrhagic background. The preoperative magnetic esonance image findings of a
      highly vascular neoplasm support the diagnosis.

PMID- 15966295
TI  - Fine needle aspiration cytology of primary proximal-type epithelioid sarcoma of
      the perineum: a case report.
AB  - BACKGROUND: Epithelioid sarcoma is a malignant soft tissue tumor of unknown
      histogenesis. We describe the cytologic findings in a case of primary proximal
      type epithelioid sarcoma of the perineum and results of an immunofluorescence
      analysis of rhabdoid cells from this tumor. To the best of our knowledge, the 3
      color immunofluorescence features of proximal-type epithelioid sarcoma have never
      before been reported. CASE: An 8-cm-diameter mass with a 2.5-cm ulcer was found
      in the perineum of a 36-year-old man. After excision of the tumor,
      histopathologic examination of the resected specimen suggested a diagnosis of
      proximal-type epithelioid sarcoma. Fine needle aspiration cytology showed
      numerous rhabdoid cells with globular intracytoplasmic inclusions. A few isolated
      cells and polygonal cells were also observed in the smears. Three-color
      immunofluorescence analysis indicated that the intracytoplasmic inclusions in the
      rhabdoid cells were positive for cytokeratin, vimentin and CD34. The cytoplasmic
      staining pattern differed between rhabdoid and epithelioid sarcoma cells.
      CONCLUSION: Immunofluorescent staining of rhabdoid cells from a primary perineal
      proximal-type epithelioid sarcoma revealed an uneven distribution of cytokeratin
      in intracytoplasmic inclusions, with the highest concentration at the periphery
      of the inclusions.

PMID- 15966296
TI  - Urine cytology of localized primary amyloidosis of the ureter: a case report.
AB  - BACKGROUND: Morphologic findings of amyloid in urine cytology material have
      rarely been reported because amyloidosis of the urinary tract is a relatively
      uncommon disorder. We present a case of primary amyloidosis of the ureter,
      including catheterized urine cytologicfindings. CASE: A 78-year-old man had
      pollakiuria and dysuria for 5 years before admission after transurethral
      resection of the prostate. Clinical examination revealed left hydronephrosis and
      stricture of the lower part of the left ureter, and a malignant ureteral tumor
      was suspected clinically. In catheterized urine cytology, many clusters of
      epithelial cells, inflammatory cells and abundant, amorphous, waxy material were
      observed. The amorphous material stained light green by the Papanicolaou method
      and positive with direct fast scarlet (DFS), showing yellow-green birefringence
      under polarized light. Positivity with DFS staining was not affected by treatment
      with potassium permanganate. Immunocytochemically the material was AL-type
      amyloid protein. Atypia were absent from epithelial cells. The patient had no
      history of diseases that could cause secondary amyloidosis. The present case was
      considered to be primary amyloidosis localized to the left ureter because no
      particular morphologic change in the epithelial cells of the urinary tract was
      observed. CONCLUSION: Amyloid can be present in urine and should not be
      overlooked or confused with tumor diathesis when a malignant tumor is suspected
      clinically.

PMID- 15966297
TI  - Cytologic findings of spindle cell ductal carcinoma in situ of the breast: a case
      report.
AB  - BACKGROUND: Ductal carcinoma in situ (DCIS), spindle cell type, is a rare and
      recently recognized entity in the breast. While the histologic features have been
      described in detail, no cytologic descriptions exist. We describe the cytologic
      and corresponding histologic findings in a case of spindle cell DCIS. CASE: A 35
      year-old woman underwent fine needle aspiration (FNA) of a 1.5-cm, palpable mass.
      The aspirate showed predominantly clusters and a smaller population of single
      cells in a necrotic background. The cells were mostly spindled, The cells were
      mostly spindled, with a minor population of epithelioid cells. They had a high
      nuclear/cytoplasmic ratio, with hyperchromatic and pleomorphic nuclei that
      contained prominent nucleoli, altogether diagnostic of malignancy. Given the
      biphasic cell composition, a diagnosis of metaplastic carcinoma was favored and
      excision recommended; it showed spindle cell DCIS. CONCLUSION: The cytologic
      features of spindle cell DCIS and metaplastic spindle cell carcinoma are similar
      and almost indistinguishable. Despite its rarity, spindle cell DCIS should be
      considered in the differential diagnosis of biphasic and spindle cell lesions in
      the breast.

PMID- 15966298
TI  - Fine needle aspiration cytology of a thyroid metastasis of metaplastic breast
      carcinoma: a case report.
AB  - BACKGROUND: Metaplastic breast carcinoma is defined as mesenchymal and/or
      squamous cell components associated with ductal carcinoma. Because of the
      heterogeneous nature of this tumor, cytologic interpretation on fine needle
      aspirates can be quite challenging. This is especially true of metastatic lesions
      of this rare tumor type. Metastasis to the thyroid has not been previously
      reported. CASE: A 57-year-old woman with a history of metaplastic breast
      carcinoma for which she underwent mastectomy, chemotherapy and radiation therapy
      2 years earlier presented with a fast-growing left thyroid mass with progressive
      hoarseness and dysphasia. Clinical presentation and findings from a neck computed
      tomographic scan were strongly suggestive of a primary thyroid malignancy. The
      aspirate specimen was composed of scant, highly atypical epithelial cells in a
      background of an abundant chondromyxoid matrix and scattered, benign follicular
      cells. A literature review confirmed the novelty of this case. CONCLUSION: This
      case emphasizes the value of clinical information and the importance of generous
      sampling in achieving a correct diagnosis of metastatic metaplastic carcinoma.

PMID- 15966299
TI  - Paratesticular spindle cell rhabdomyosarcoma diagnosed by fine needle aspiration
      cytology: a case report.
AB  - BACKGROUND: Spindle cell rhabdomyosarcoma is a rare, newly identified subtype
      ofembryonal rhabdomyosarcoma with improved behavior and a predilection for the
      paratesticular area. Fine needle aspiration (FNA) cytology findings of embryonal
      rhabdomyosarcoma have been described. However, there is no previous report on the
      cytologic findings of spindle cell rhabdomyosarcoma at testicular or
      extratesticular sites. CASE: A 13-year-old boy presented with a large, right
      sided scrotal mass. Fine needle aspiration (FNA) was performed for rapid
      diagnosis. The smears revealed numerous spindle cells and large fragments of
      cytoplasmic processes with cross-striations and were diagnosed as spindle cell
      rhabdomyosarcoma. The histologic sections were also diagnosed as spindle cell
      rhabdomyosarcoma. CONCLUSION: The cytologic findings of this rare tumor have not
      been reported before. The cross-striations were easily identified in FNA smears,
      so the diagnosis of spindle cell rhabdomyosarcoma was made confidently. The
      histologic sections showed only spindle cells with different patterns of
      arrangement, resembling leiomyosarcoma. The cross-striations were not identified
      in the histologic sections. In this case cytologic diagnosis aided the histologic
      diagnosis.

PMID- 15966301
TI  - Secretory carcinoma of the breast diagnosed by fine needle aspiration.

PMID- 15966300
TI  - Chronic wuchereriasis presenting as a vaginoperineal fistula: report of a case
      with aspiration cytologic diagnosis.
AB  - BACKGROUND: Filariasis is often an occult disease with myriad presentations.
      Cytology has an established role in diagnosing clinically unsuspected cases.
      CASE: A 20-year-old female presented with recurring perineal ulcers, vaginal
      discharge and inguinal lymphadenopathy. Radiology revealed a vaginoperineal
      fistula. Fine needle aspiration (FNA) of the ulcer bed and smears prepared from
      the ulcer discharge showed an adult, gravid, female filarial worm and unsheathed
      larvae. Similar microfilariae were also seen in FNA smears from inguinal lymph
      nodes. The atypical clinical presentation and unusual parasite morphology posed
      initial difficulties in characterization of the microfilarial species.
      CONCLUSION: This case report highlights the morphologic clues to the dif
      ferential diagnosis offilarial species on cytologic specimens. Chronic
      wuchereriasis presenting as a vaginoperineal fistula has not been reported
      previously.

PMID- 15966302
TI  - Fine needle aspiration cytology of tubular carcinoma of the breast.

PMID- 15966303
TI  - Frozen shoulder as the initial presentation of gallbladder cancer diagnosed by
      fine needle aspiration cytology.

PMID- 15966304
TI  - Sinus histiocytosis with massive lymphadenopathy: diagnosis by fine needle
      aspiration.

PMID- 15966305
TI  - Fine needle aspiration of precursor B lymphoblastic leukemia in an adult
      presenting as disseminated skin nodules.

PMID- 15966306
TI  - Study IDs 8 keys to success for capitated groups.

PMID- 15966307
TI  - Florida 2005 Medicaid HMO capitation rates show breakdown by age, region,
      eligibility.

PMID- 15966308
TI  - Benchmark your senior population against these health status costs, indicators.

PMID- 15966309
TI  - [Vascular-specific promoters and cis-regulatory elements].
AB  - Vascular-resided bacterial and fungal diseases have caused a great deal of yield
      loss and quality reduction in crop production world-wide. For genetic engineering
      of crops resistant to these diseases, it is disirable to have a strong and
      vascular-specific promoter. This article reviews the progress in identification
      of vascular-specific promoters and its function. To date, roughly twenty vascular
      specific promoters have been documented. The cis-elements and motifs have been
      studied in detail for the promoters of bean phenylalanine ammonia lyase (PAL2),
      bean glycine-rich protein (grp 1.8) and Arabidopsis profilin2 (pfn2) in
      particular.The motif of vs-1 (CATGCTCCGTTGGATGTGGAAGACAGCA) found in grp 1.8
      promoter was a cis-element that specificically bind to a transcription activation
      factor VSF-1 protein (one of the bZIP proteins). Mutation of vs-1 prevented it
      from binding to VSF-1 that resulted in abolishing the vascular-specific expresson
      of gus gene. Motifs of AC-I and AC-II found in PAL2 promoter were also found to
      be essential for vascular-specific expression. In our laboratory we have
      dissected pfn2 promoter into three domains (A, B, C) through 5'-deletion
      analysis. In this promoter we have identified two core sequences of ACGT that is
      commonly found in the binding sites of bZIP protein, the most abundent
      transcription factor existed in plants. In additon, the pfn2 promoter also
      contains an AC- I like sequence (CCACCTAC) that is similar to the AC- I motif
      (CCCACCTACC) found in PAL2 promoter. These promoters and cis-elements may have a
      wide range of potential applications to the genetic improvement of crops
      resistant to vascular diseases.

PMID- 15966310
TI  - [Advances of studies on mesenchymal stem cells].
AB  - Bone marrow mesenchymal stem cells (MSCs) are defined as pluripotent cells which
      have high self-renewal capacity and multipotentiality for differentiation.
      Because of their characteristics of supporting hematopoietisis, multipotentiality
      for differentiation and their possible use for both cell and gene engineerings,
      MSCs will have important value in clinic use.

PMID- 15966311
TI  - [The potential of avian cytokines as immunotherapeutics and vaccine adjuvants].
AB  - With the imminent and widespread ban of the use of antibiotic feed additives and
      chemical antimicrobials in food production animals, alternative measures need to
      be sought to ensure that the livestock industry will not be adversely affected.
      Cytokines are proteins that control the type and extent of an immune response
      following infection or vaccination. They therefore represent excellent naturally
      occurring therapeutics. The identification, cloning and characterisation of
      cytokine genes in chickens have lagged somewhat behind similar work in mammals.
      Progress in isolating chicken homologues of mammalian cytokines has also been
      slowed by the generally low level of sequence similarity. Chicken cytokine genes
      that have been cloned to date include ChIFN-gamma, ChIL-1beta, ChIFN-alpha, ChIL
      15, ChIL-18, ChIL-8, ChIL-2, ChIL-6, ChIL-16, SCF, MGF, TGFbeta, Lymphotactin,
      MIP-1beta, CXC and CC chemokines, so the use of cytokines in poultry has become
      more feasible with the discovery of a number of avian cytokine genes. The
      delivery methods for chicken cytokine are of prime importance and are required to
      be safe, easy to administer and cost-effective. Live viral vectors such as fowl
      adenovirus (FAV) expressing cytokine genes can be delivered via drinking water or
      aerosol sprays, making it very easy to administer. Since the immune system of
      chickens is similar to that of mammals, they offer an attractive model system to
      study the effectiveness of cytokine therapy in the control of disease in
      livestock. This review focus on the recent advances made in avian cytokines, with
      a particular focus on their assessment as therapeutic agents and vaccine
      adjuvants.

PMID- 15966312
TI  - Identification and expression analysis of a full-length cDNA encoding a Kandelia
      candel tonoplast intrinsic protein.
AB  - Soil salinity is an important issue, as most crop plants are low in salt
      tolerance. Salt tolerance, a complex, multifactorial, and multigenic process, has
      been known to be a quantitative trait. The identification of the salt stress
      responsive genes or salt tolerance genes is essential for the breeding programs.
      Most recent efforts have been focused on the products of structural genes
      (transport proteins, ion channels, enzymes of solute synthesis) while little
      attention were paid to the regulatory aspects of these proteins. Since the first
      aquaporin gene from plants was cloned and functionally expressed in 1993, there
      has been a growing interest in the molecular biology of MIPs (membrane intrinsic
      proteins) and their bearing on the biophysics of water flow across plant
      membranes. In the last decades, studies on Mangroves, a special kind of wood
      plants, grow in high-salt and flooding conditions have been concentrated almost
      exclusively on their physiological and ecological characteristics. Kandelia
      candel, one of the dominant species of mangroves along the Chinese coast, lacks
      salt glands or salt hairs used for removal of excess salt in other mangroves.
      This makes K. candel a perfect model to study the molecular mechanism of salt
      tolerance in mangrove plants. Using cDNA RDA, a cDNA-specific modification of
      genomic representational difference analysis, a series of salt responsive genes
      of Kandelia candel were cloned. Among these gene fragments, a 183 bp fragment
      (termed as SRGKC1) encoding a tonoplast intrinsic protein (TIP) in Kandelia
      candel (KCTIP1) was identified. Based on the sequence of SRGKC1, two gene
      specific primers were designed, and the 3' and 5' end of the KCTIP1 gene were
      obtained using the SMART RACE cDNA Amplification Kit. RACE products were purified
      from low-melting agarose, and sequenced directly with GSPs as the sequencing
      primers. A 500-bp fragment corresponding to the 3'end of this gene was obtained
      using the GSP1 primer, and a 690 bp fragment corresponding to the 5' end of this
      gene was obtained using the GSP2 primer. Two primers that flank the putative open
      reading frame (ORF) were designed to obtain the cDNA containing the complete ORF
      by RACE PCR reaction. The full-length cDNA of KCTIP1, containing a 756 bp open
      reading frame (ORF), was approximately 1.1 kb; the start codon was located at the
      nucleotides of 99-101 and stop codon at the nucleotides of 855-857 followed by a
      poly (A) tail. The KCTIP1 cDNA sequence in this research was released in GenBank
      with accession number AF521135. Using ExPASy Proteomics tools provided by EMBL,
      the isoelectric point and MWt of KCTIP1 are estimated as 5.77 and 26.3 kD
      respectively. Transmembrane prediction analysis revealed the deduced KCTIP1
      protein sequence contains six transmembrane regions at amino acid residues of 20 
      42, 57 - 79, 86 - 108, 113 - 135, 142 - 164 and 217 - 239. Two highly conserved
      asparagine-proline-alanine (NPA) motifs were located at 85 - 87 and 199 - 201
      amino acid residues respectively. KCTIP1 is also predicted to contain the Cys
      residue (Cys 118) that are shown to confer Hg-sensitivity in Arabidopsis gamma
      TIP and delta-TIP. Similarity analysis showed that KCTIP1 shared 77% - 79% amino
      acid sequence identity with the TIPs from Vitis berlandieri, Brassica oleracea
      and Arabidopsis thaliana. Expression analyses indicated that KCTIP1 had different
      expression among species of Mangroves. Expressions of KCTIP1 in Kandelia candel,
      Rhizophora apoculata and Ceriops tagal were suppressed by salt, and were
      insensitive to salt stress in unknown species of Mangroves. Previous studied
      showed that salt conditions might result in large and rapid changes in
      extracellular water potential and serious disturbance to the cytoplasm. In order
      to compensate for this imbalance, the relative contribution of water channels to
      flow across the root could thus vary. K. candel is a species that is native to
      intertial zone of tropical and subtropical coast and is well-adapted to salt
      conditions. The coordinated down-regulation of aquaporins in this plant may
      decrease membrane water permeability and thus increase the cellular water
      conserva- tion during periods of salt stress. The results reported here are
      consistent with the postulated roles for tonoplast water channels in regulating
      the hydraulic permeability of the vacuolar membranes and in adjusting the water
      homeostasis of the protoplasm under various physiological conditions. The
      identification of KCTIP1 as one of salt-responsive genes implies that
      intracellular osmotic equilibration is a part of salt-tolerant mechanisms in
      Mangroves.

PMID- 15966313
TI  - [Accelerated improvement of bacterial blight resistance of 'Shuhui527' using
      molecular marker-assisted selection].
AB  - 'Shuhui527' is a promising restorer line bred by Rice Research Institute of
      Sichuan Agricultural University in recent years. However, this line is
      susceptible to Bacterial Blight (BB), which limits its use. The IRBB60, from the
      International Rice Research Institute (IRRI), contains dominant genes Xa21 and
      Xa4 conferring resistance to BB. The objective of this study is to improve the BB
      resistance of 'Shuhui527' by introgressing Xa21 and Xa4, the two broad-spectrum
      BB resistance genes, into 'Shuhui527' with IRBB60 as the donor, pTA248 and MP12,
      linking tightly with Xa21 and Xa4 respectively as DNA markers. BC1 F1 progenies
      of (Shuhui527 x IRBB60), containing Xa21 and Xa4 identified using PCR screening
      and with agronomic traits including plant type, grain type and days to heading
      etc similar to those of 'Shuhui527', were subsequently backcrossed to 'Shuhui527'
      and self-pollinated to generate BC2 F1 and BC1 F2 . The BC3 F1 and BC3 F2 were
      subsequently developed using the same approach. Among the 20 BC3 F2 plants,
      homozygous Xa21 and Xa4,10 plants were the most similar to 'Shuhui527' in the
      agronomic traits, and were screened using 120 pairs SSR and 100 pairs RAPD
      markers. Based on the results of the background screening and the performance of
      the agronomic traits, 5 plants were identified as improved-'Shuhui527' and
      designated as 527R-5, 527R-6, 527R-8, 527R-9 and 527R-10. The improved-'
      Shuhui527' lines expressed high resistance to Xanthomonas oryzae pv . oryzae
      (Xoo) stains C I - C VII, P1 and P6. The evaluation of the polymorphisms and
      selection accuracies of pTA248 and MP12 demonstrated that the polymorphisms of
      the two markers were obvious and co-dominant and the accuracies were more than
      97% and 83% respectively, indicating the two markers are good for Xa21 and Xa4 in
      Molecular Marker-assisted Selection.

PMID- 15966314
TI  - [Enhancement of cellular immune response to DNA vaccine encoding hepatitis C
      virus core and envelope 2 fusion antigen by murine Fms-like tyrosine kinase 3
      ligand].
AB  - Hepatitis C virus (HCV) is an important human pathogen that causes chronic liver
      disease worldwide. It is desirable to develop vaccines to prevent HCV infection,
      or at least to prevent progression to chronicity. We once constructed an
      optimized hepatitis C virus core and envelope 2 fusion antigen DNA vaccine, which
      could induce humoral and cellular immune responses against HCV core and E2
      protein in BALB/c mice efficiently. Flt3 (Fms-like tyrosine kinase 3) -ligand has
      been identified as an important cytokine for the generation of professional
      antigen-presenting cells, particularly dendritic cells. We reasoned that a DNA
      vaccine coexpressing the antigen and FL may activate immune responses more
      effectually. In this study, The influence of FL on this HCV DNA vaccine was
      evaluated. The cDNA encoding signal peptide and extracellular domain of murine FL
      was inserted into the plasmid pST-CE2t, and the resulting plasmid pST-CE2t/FL was
      transfected into COS7 cells. The HCV core and E2 protein were detected by Western
      blotting, and the soluble murine FL was detected by ELISA. Eight-week-old female
      BALB/c mice were inoculated intramuscularly with 100 microg pST-CE2t, pST-CE2t/FL
      or mock vector, respectively, and boosted at the same dosage 3 weeks later. Anti
      HCV core and E2 total IgG and isotypes were measured at weeks 1,3,5,7. Splenocyte
      proliferative response to recombinant HCV core and E2 protrein were detected at
      week 7. SP2/0 cells expressing HCV core protein were used as target cells for the
      detection of cytotoxic T lymphocyte (CTL) response. Western blot analysis showed
      that a protein band with molecular weight about 70 kD from lysate of COS7 cells
      transfected with plasmid pST-CE2t/FL could be detected by anti-HCV core or E2
      monoclonal antibodies, which indicated that pST-CE2t could express glucosylated
      HCV core and E2 fusion protein. Murine FL could be detected in the culture
      supernatant of COS7 cells transfected with pST-CE2t/FL. Plasmid pST-CE2t
      immunized mice developed higher anti-HCV core and E2 IgG seroconversion rates and
      titers than pST-CE2t/FL group did at different various times, but the IgG2a/IgG1
      ratio of anti-HCV E2 protein in pST-CE2t/FL group is much higher than pST-CE2t
      group. Splenocytes from pST-CE2t or pST-CE2t/FL immunized mice could proliferate
      with stimulation of HCV core or E2 protein in vitro, although pST-CE2t/FL group
      showed much stronger response. Splenocytes from mice immunized with pST-CE2t/FL
      induced 79.03% +/- 9.95% of target cell lysis at the effector/target ratio of
      100:1, which was significantly greater than the lysis (62.2% +/- 8.62%) observed
      in mice immunized with pST-CE2t. Our data demonstrated that the incorporation of
      FL can preferentially enhance the cellular response to this HCV fusion antigen
      DNA vaccine. In contrast, HCV specific antibodies were inhibited by FL in
      vaccinated mice. More and more data supports that recovery from acute HCV
      infection may depend upon the generation of broad-based cellular immune responses
      to viral proteins. So, FL may be of potential value as an adjuvant in the
      development of DNA-based immunization for prophylactic and therapeutic vaccine
      against HCV infection.

PMID- 15966315
TI  - [Expression of a DNA fragment encoding the active domain of human TNF related
      apoptosis inducing ligand in pichia pastoris].
AB  - Human tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) is a member
      of the tumor necrosis factor (TNF) family of ligands which has been reported in
      1995. The TRAIL protein induces apoptosis of certain types of target cells, such
      as transformed cells that include but are not limited to cancer cells and virus
      infected cells but the normal cells. It is a type II transmembrane protein and
      the extracellular domain of TRAIL is the functional domain in induction of cell
      apoptosis. A gene fragment encoding for the active domain of TRAIL was modified
      with oligo-nucleotide directed mutagenesis according to the characters of Pichia
      pastoris expressing vector. Arginine at the position of 149 corresponding to the
      amino acid residue 531 which might be a potential Kex2 protease processing sites
      was substituted with Lysine to prevent the expressed protein from the digestion
      by the protease. After proved with DNA sequencing. the modified gene fragment
      coding soluble TRAIL domain was inserted into the Pichia pastoris expression
      vector pPIC9K in the same reading frame with alpha-factor secreting signal
      peptide. The recombinant plasmid pPIC9K - TRAIL was transferred into P. pastoris
      cell by spheroplast transformation. The recombinant yeasts were identified by
      antibiotic G418 and Southern dot blot. The transformants (His+ Mut(s)) containing
      multi-copy gene fragment of TRAIL were selected with increasing concentration of
      G418 and induced with 0.5% methanol in shaking flask to expression the active
      domain of TRAIL. After inducing for 3 - 4 days, the proteins in the culture
      supernatant was assayed with SDS-PAGE and Western blot. Two expressed protein
      bands whose appearant molecular weight were 19kD and 38kD, respectively, could be
      specifically recognized by polyclonal antibodies against human TRAIL. The 38kD
      protein might be a dimers of TRAIL in the culture supernatant. The amount of
      expressed foreign protein made up to 36% of the total proteins in the culture
      suprenatant. Biological activity assay, in vitro, indicated that the expressed
      protein could induce tumor cells apoptosis.

PMID- 15966316
TI  - [Establishment of stably expressed human RANTES gene in prunella vulgaris cell
      clone].
AB  - To express interesting human genes in herbal cells for boosting their specific
      pharmacological activities, RANTES gene cloned from human peripheral blood
      lymphocyte (PBL) mRNA was introduced into A. tumefaciens strain LBA4404 harboring
      pAL4404 plasmid via tumor-inducing (Ti) plasmid-derived intermediate expression
      vector pROKII. In vitro cultured P. vulgaris cells were transformed by leaf-disk
      cocultivation procedure. Integration of RANTES gene in the genome of transformed
      cells was confirmed by Southern blotting, and expression of RANTES gene in
      transformed cells was analyzed by RT-PCR amplification, Western blotting and
      enzyme-linked immunosorbent assay (ELISA). The peroxidase activity of PBL was
      utilized as a detection index of cellular chemotropism induction by recombinant
      RANTES. The results have shown the RANTES gene was integrated in transgenic P.
      vulgaris cells, and RANTES gene-stably expressed cell clones were available,
      which could pave the way to obtain transgenic P. vulgaris plants demonstrating
      specific pharmacological activities.

PMID- 15966317
TI  - [Cloning and expression of L-N-carbamoylase gene from Arthrobacter BT801 in
      Escherichia coli].
AB  - Hydantoin-utility-enzyme is widely used in enzymic production of various amino
      acids. One of its component, carbamoylase, is responsible for the conversion of N
      carbamylamino acids to corresponding amino acids, which is crucial for the
      stereoselectivity and rate limiting. To improve the production of the enzyme, an
      L-N-carbamoylase gene from Arthrobacter BT801, a hydantoinase producting strain
      being able to convert 5-benzylhydantoin to phenylalanine, was cloned into E.
      coli. The gene was highly expressed in E. coli M15 under control of T5 promoter.
      A protein band about 44kD was detected by SDS-PAGE in the recombinant cell
      lysate. The objective product, which is principally in soluble form, represented
      40% of total cell protein. The N-carbamoylase specific activity of the
      recombinant M15/pQE60- hyuC is 53 times higher than that of Arthrobacter BT801.
      The total biotransformation activity increased 8.1 times when. M15/pQE60-hyuC was
      added into the Arthrobacter BT801 reaction system. The successful expression of
      the enzyme is significant for the application of the hydantoinase producing
      strain or the enzyme thereof.

PMID- 15966318
TI  - [Expression of Mortierella isabellina delta6-fatty acid desaturase gene in gamma
      linolenic acid production in transgenic tobacco].
AB  - Gamma-linolenic acid (GLA, C18:3delta6.9.12) is nutritional and important
      polyunsaturated fatty acid in human and animal diets. GLA play an important role
      in hormone regulation and fatty acid metabolization. Furthermore it is also the
      biological precursor of a group of molecules, including prostaglandins,
      leukotrienes and thromboxanes. Vast majority of oilseed crops do not produce GLA,
      but linoleic acid (LA, C18:2delta9.12) as its substrate. GLA is only produced by
      a small number of oilseed plants such as evening promrose ( Oenotheera spp.),
      borage (Borago officinalis) and etc. delta6-fatty acid desaturase (D6D) is the
      rate-limiting enzyme in the production of GLA. It can convert from linoleic acid
      to linolenic acid. To produce GLA in tobacco, plant expression vector was first
      constructed. To facilitate preparation of plant expression constructs, flanking
      Xba I and Bgl II restriction enzyme sites were added to the coding region of
      clone pTMICL6 by PCR amplification. pTMICL6 contains delta6-fatty acid desaturase
      gene cloned from Mortierella isabellina which is an oil-producing fugus. The PCR
      product was purified and subcloned into the plant expression vector pGA643 to
      generate the recombinant vector pGAMICL6 which contains the ORF of the D6D gene
      of Mortierella isabellina, together with regulatory elements consisting of the
      cauliflower mosaic virus 35S promoter and the nopaline synthase (nos) termination
      sequence. The plasmid pGAMICL6 was transformed into Agrobacterium tumefaciens
      strain LBA4404 by method of freeze thawing of liquid nitrogen. Transformants were
      selected by plating on YEB medium plates containing kanamycin and streptomycin
      and grown overnight at 28 degrees C, then transformants were further identified
      by PCR. The positive transformant containing the plant expression vector pGAMICL6
      was transformed into tobacco ( Nicotiana tabacum cv. Xanthi) via Agrobacterium
      infection. Transgenic plants were selected on 100 microg/mL kanamycin. Plants
      were maintained in axionic culture under controlled conditions. Total nucleic
      acids were extracted and purified from anti-kanamycin transgenic tobacco and were
      analysed by PCR. 48 out of 80 transgenic plants were positive, in other words,
      transformation efficiency is 60% . This shows that Mortierella isabellina D6D
      gene is transformed into tobacco. Genomic DNA from PCR positive transgenic
      tobacco plants was digested with Hind III restriction enzyme and fractionated by
      agarose gel electrophoresis. Southern blotting was performed with strandard
      procedures for vacuum transfer of nucleic acids to nylon membrane. The probe was
      delta6-fatty acid desaturase gene from M. isabellina, which was labeled with DIG
      dUTP via random-primed labeling. Hybridization and immumological detection were
      carried out the kit of DIG detection. The result shows single hybridizing bands
      in each of the transgenic tobacco plants DNA, but no hybridization was observed
      to non-transgenic tobacco. This indicates that delta6-fatty acid desaturase gene
      is integrated into the genome of transgenic tobacco. To provide further evidence
      that the introduction of the M. isabellina cDNA into the tobacco genome was
      responsible for the novel desaturation products, total RNA was isolated from GLA
      positive transgenic tobacco plants via both PCR and Southern blotting and
      separated by electrophoresis through 1% formaldehyde agarose gel. Northern
      blotting including probe labeling, hybridization and detection was the same as
      Southern blotting in operation approach. A positive hybridization signal of
      identical mobility was obtained from RNA isolated from the transgenic tobacco
      plants, but not from the control tobacco plant. At last, total fatty acids
      extracted from the positive transgenic tobacco were analyzed by gas
      chromatography (GC) of methyl esters to confirm the transgenic tobacco containing
      a functional delta6-fatty acid desaturase gene. The result shows that two peaks
      were observed in the chromatogram of FAMes. GLA and octadecatetraenoic acid (OTA,
      C18:4delta6.9.12.15) respectively have 19.7% and 3.5% of the total fatty acids in
      the transgenic plant. The presence of both GLA and OTA indicates that the delta6
      fatty acid desaturase used both linoleic acid and a-linolenic acid (ALA,
      C18:3delta6.9.12.15) as substrates, and this may be responsible for the decrease
      in ALA observed in the transgenic line. That was the first report about the
      expression of M. isabellina delta6-fatty acid desaturase gene in tobacco. All
      results mentioned above have laid the foundation of the thorough studying on an
      breeding transgenic oilseeds containing GLA to change the fatty acid composition
      of conventional oilseeds, it is significant to study on regulation mechanism of
      fatty acid desaturase.

PMID- 15966319
TI  - [Site-directed mutagenesis of NisinZ and properties of NisinZ mutants].
AB  - According to the knowledge gained from engineering of nisinZ, using plasmid
      pHJ201 DNA as template, NisinZ was mutated by site-directed mutagenesis, NisinZ
      mutant T8S contains Serine at position 8 instead of Threonine, NisinZ mutant
      N27K/H31K contains Lysine at position 27 and 31, respectively, instead of
      Asparagine and Histidine and NisinZ mutant T2S/ H31K contains dehydrobutyrine and
      Lysine at position 2 and 31 instead of dehydroalanine and Histidine. They are
      cloned into pMG36e and expressed in L. Lactis NZ9800, the expression products of
      these mutants purified by Sephadex CM-25 and Sephadex G-25 chromatography, some
      properties of NisinZ mutants (T8S, T2S/H31K and N27K/H31K) were studied. The
      results showed that the spectrum of antimicrobial activity and solubility of
      these mutants had not been changed, their antimicrobial activities were found to
      be slightly lower than that of the wild-type NisinZ. but mutants T8S and T2S/H31K
      showed higher stability, which were significantly more stable than wild-type
      NisinZ at 55 approximately 100 degrees C and pH7 approximately 9.

PMID- 15966320
TI  - [Screening of new binding partners of CIKS with yeast two-hybrid system].
AB  - The NF-kappaB transcription factor plays important regulatory roles in
      inflammation, apoptosis, immune and stress responses. IkappaB kinase (IKK)
      composed of two catalytic subunits and a regulator subunit, acts as a key
      component of NF-kappaB activation pathway through phosphorylation of IkappaB, the
      inhibitor of NF-kappaB. CIKS (connection to IKK and SAPK), a newly identified
      cellular protein, is involved in NF-kappaB and JNK activation. Although it has
      been known that CIKS interacts with IKK complex, and activates both IKK and SAPK
      when overexpressed; the underling mechanisms are poorly understood. To better
      understand the physiological roles of CIKS, we have screened human HeLa
      MATCHMAKER cDNA library for new binding partners of CIKS by using the yeast two
      hybrid system with truncated CIKS (151-574) as the bait. The yeast strain AH109
      was sequentially transformed with the bait plasmid and the library. The
      transformants were screened on SD(-Leu/-Trp/-His/-Ade/ + X-alpha-gal)selective
      plates. Positive clones were restreaked on SD(-Leu/-Trp / + X-alpha-gal)plates
      three times to allow loss of some of the AD/library plasmids while maintaining
      selective pressure on both the DNA-BD and AD vectors. After 3 screenings on SD(
      Leu/-Trp / + X-alpha-gal), the positive clones were further verified on SD(-Leu/
      Trp/-His/-Ade/ + X-alpha-gal) plates. The inserts in AD/library plasmids were
      amplified by PCR and PCR products were characterized by Hae III digestion to
      eliminate the duplicates. After screening in selective plates, the positive
      AD/library plasmids were rescued via transformation of E. coli HB101 and the
      interactions of CIKS (151-574) with positive AD/library plasmids were further
      assessed by yeast two-hybrid analysis. Finally, the DNA sequences of the positive
      AD/library plasmids were determined and BLAST analysis against the databases was
      performed. The BLAST results indicate that the inserts in the positive plasmids
      encode RIKEN cDNA 473340F03, PLAC8, CD27BP (Siva-1), CDC5L, SnRNP smB, and DVL2.
      CDC5L is a key component of the multi-protein complex essential for the formation
      of pre-mRNA splicing product and is not required for spliceosome assembly. A role
      for CDC5L in the cell division cycle has been precious suggested as its
      overexpression of this protein in mammalian cells leads to a shortening G2 phase
      of the cell cycle, and a negative-dominant mutant of CDC5L lacking the N-terminal
      activation domain delays the G2 phase cell's entry into the mitosis. It has been
      reported that SnRNP smB participates in pre-mRNA splicing and CD27BP (Siva-1)
      binds to and inhibits BCL-XL-mediated protection against UV radiation-induced
      apoptosis and regulates T cell homeostasis. The functions of RIKEN cDNA
      473340F03, PLAC8 and DVL2 are unknown. It has been suggested that CIKS functions
      as a critical component for cross-talk between NF-kappaB and JNK signaling
      pathways. IKK subunits, which have been demonstrated to interact with CIKS, were
      not shown up in this experiment. We speculate that the truncated CIKS (151-574)
      bait may not contain the binding domain that mediates the interaction of IKK
      subunits with CIKS. Taken together, the above results suggest that CIKS may play
      a role in cell regulation through interacting with various cellular proteins.
      Further investigations are required to characterize these interactions.

PMID- 15966321
TI  - Biosynthesis of poly (3-mercaptopropionate) and poly (3-mercaptopropionate-co-3
      hydroxybutyrate) with recombinant Escherichia coli.
AB  - Polythioesters newly emerged as a type of novel polymer and they have showed
      great potential for application in industries. In this study, genes of butyrate
      kinase (buk) and phosphotransbutyrylase (ptb) from Clostridium acetobutylicum,
      and poly (3-hydroxybutyrate) (PHB) synthase gene from Thiocapsa pfennigii were
      used for construction of a metabolic pathway to synthesize the polythioesters.
      When 3-mercaptopropionate and 3-hydroxybutyrate were fed, poly (3
      mercaptopropoinate) [poly (3MP)] and poly(3-mercaptopropionate-co-3
      hydroxybutyrate) [poly(3MP-co-3HB)] were synthesized by recombinant Escherichia
      coli JM109 (pBPP1) harboring the constructed metabolic pathway. Results indicated
      clearly that all these genes are necessary for the synthesis of poly(3MP) and
      poly(3MP-co-3HB).

PMID- 15966322
TI  - [Quantitation & optimization of guanosine fermentation process: prevention of
      NH4+ accumulation increases guanosine production by 70%].
AB  - Metabolic engineering has become a powerful tool for optimization of industrial
      fermentation processes. Metabolic engineering usually undergoes three steps:
      construction of a recombinant strain with improved properties, genetic and
      biochemical analysis of the strain, and identification of target for further
      improvement. Metabolic fluxes analysis is an important part of the biochemical
      analysis. Based on the law of mass conservation and assuming pseudo-steady-state
      for the intermediates in the metabolic pathways, we have quantitatively analyzed
      the time course of the flux distribution in Bacillus subtilis and used the data
      to reveal the nature of the so-called "40 hour" phenomenon in fermentation of
      guanosine, a key raw material for the synthesis of additives for human
      consumption and animal feeds. The phenomenon refers to the observation that
      guanosine production, which proceeds at high rate from 12 hour on, declines
      around 40 hour while consumption of glucose keeps increasing, leading to the
      lower yield of the nucleoside. Equations based upon the metabolic network of
      Bacillus subtilis consisted of EMP pathway, HMP pathway, TCA cycle, oxidative
      phosphorylation pathway and others reactions of the intermediates, was
      constructed. The equations were solved by using the quantitative data obtained in
      this study. The air flow and volume, concentration of oxygen and carbon dioxide
      in the exit-gas were monitored online; the concentration of biomass, glucose and
      guanosine was analyzed manually; and the concentration of acetate, citric acid,
      pyruvate, and 17 amino acids were HPLC quantified. The solutions of the equation
      were proved to be valid, as the experimental data on oxygen consumption agrees
      with that of predicted form the equation. The results indicated that at 40h of
      the fermentation process the flux of HMP pathway, which provides the precursor of
      the nucleoside, decreased while that of EMP pathway and the pathways that
      generate amino acids and organic acids increased. The shift correlated with the
      accumulation of NH4+ in the broth. The assimilation of NH4+ is an energy
      consuming process and could shift the metabolism to the energy generating EMP
      pathway. Accordingly, measures were taken to prevent the accumulation of NH4+.
      The interference indeed stopped the metabolism shift and boosted the guanosine
      production at 30 g/L, 70% higher than the level reported in literature.

PMID- 15966323
TI  - [Saccharomyces cerevisiae B5 efficiently and stereoselectively reduces 2'
      chloroacetophenone to R-2'-chloro-1-phenylethanol in the presence of 5% ethanol].
AB  - (R)-chlorprenaline, a selective activator of beta2 receptor and an effective drug
      for bronchitis and asthma, is industrially prepared from (R)-2'-chloro-1-phenyl
      ethanol. In this communication, we describe (1) the identification of
      Saccharomyces cerevisiae B5 as an effective host for stereoselective reduction of
      2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol; (2) the presence of
      ethanol enhances the conversion; and (3) the biochemical factors that effect the
      yield of the product. Among the four yeast strains capable of reduction 2'
      chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol we screened, Saccharomyces
      cerevisiae B5 showed the highest activity and stereoselectivity, and was used for
      the subsequent study. The effect of the presence of methanol, ethanol, 2
      propanol, 1-butanol, glucose, glycerol and lactic acid was first investigated, as
      it was previously reported that they increased the yield and stereoselectivity of
      the reaction. The addition of the co-substrate methanol, ethanol, 2-propanol, 1
      butanol, glucose and glycerol favored the formation of the 2'-chloroacetophenone
      to (R)-2'-chloro-1-phenyl-ethanol. Lactic acid inhibited the enzyme activity.
      Ethanol is the best co-substrate among the seven co-substrates and under the
      optimum concentration of 5% , the yield of (R)-2'-chloro-1-phenyl-ethanol was
      increased from 17% to 74%. The oxidation of ethanol regenerates NADH required for
      the reduction. The effects of the reaction time, pH, cell concentration,
      substrate concentration and temperature on the reduction were investigated next.
      The enantiometric excess of (R)-2'-chloro-1-phenyl-ethanol reached 100% under the
      optimal condition: pH8.0, 25 degrees C and 5% ethanol. The product yield went up
      with the increasing Saccharomyces cerevisiae B5 concentration and reached 100%
      when the cell dry weight was 10.75 mg/mL and 2'-chloroacetophenone was 6.47
      mmol/L. The yield of (R)-2'-chloro-1-phenyl-ethanol decreased sharply with the
      increase of substrate concentration, as the high concentration of substrates is
      toxic to the cell and inhibits the activity of reductases. The aerobic
      cultivation of the yeast and shaking during the reaction increased the yield of
      (R)-2'-chloro-1-phenyl-ethanol. The yeast can be reused up to 15 times. This
      research paves the way for economical preparation of chiral 2'-chloroacetophenone
      to R-2'-chloro-1-phenylethanol.

PMID- 15966324
TI  - [Effects of nutrient conditions and fed-batch culture on CoQ10 production by
      Rhizobium radiobacter WSH2601].
AB  - The effects of the variables, including the concentrations of glucose, sucrose,
      corn steep liquor (CSL) and peptone, and the conditions of fed-batch culture, on
      CoQ10 fermentation by Rhizobium radiobacter WSH2601 were assessed. The results
      showed that the optimum concentrations of glucose, sucrose, CSL and peptone were
      30 g/L, 40 g/L, 11 g/L and 16 g/L respectively. Addition of CSL and tomato juice
      stimulated the cell growth. CSL, L-methionine and isopentyl alcohol efficiently
      increased the biosynthesis of CoQ10. In a 7L fermentor, the fed-batch culture
      improved both cell growth and CoQ10 production compared to a batch culture; and
      suitable mixed feeding of CSL and sucrose enhanced CoQ10 yield to 52.4 mg/L. The
      DCW reached 26.4 g/L, an increase of 53% in comparison to that without feeding,
      and an increase of 24% to that feeding with sucrose only. The C/B value reached
      2.38 mg/g(DCW), representing an increase of 33% to that of without feeding, and
      an increase of 26% to that of feeding with sucrose only.

PMID- 15966325
TI  - [Preparation and functional study of an adenovirus vector expressing human
      plasminogen kringle 5 gene].
AB  - Tumor angiogenesis plays a pivotal role in the progress of tumor. Among the
      various endogenous angiogenic inhibitors discovered, the human plasminogen
      kringle 5 (K5) has been demonstrated to be a potential inhibitor of the
      proliferation and migration of vascular endothelial cells in vitro. The
      replication-incompetent adenovirus (Ad) vector Adeno-X-CMV-K5 (Ad-K5) (where CMV
      is cytomegalovirus) was constructed and its antiangiogenic effect was tested on
      vascular endothelial cell and tumor cell. For the construction, the K5 cDNA was
      fused in-frame with human plasminogen signal sequence and inserted into the
      eukaryotic expression vector pcDNA3 to form pcDNA3K5. The recombinant plasmid was
      subcloned into the shuttle plasmid pShuttle under the control of the constitutive
      CMV immediate-early promoter. The plasmid carrying the cDNA for K5 (pShuttleKS)
      was then recombined with the Adeno-X viral DNA and transformed into E. coli
      DH5alpha. The resultant recombinant plasmid pAd-K5 was transfected into human
      embryonic kidney (HEK) 293 cells with liposome. The adenovirus expressing human
      plasminogen kringle 5 (Ad-K5) was successfully packaged and propagated in 293
      cells, as detected by the cytopathic effect (CPE) on the cells, and the viral
      titer in the supernatant was 5 x 10(8) pfu/mL by plaque assay. Both human
      umbilical vein endothelial cell line ECV304 and human breast carcinoma cell line
      MDA-MB-231 were infected with Ad-K5 and Ad-LacZ, which was used the negative
      control, and assayed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide) assay. Compared with uninfected control and Ad-LacZ infected control, Ad
      K5 infected group at 80 MOI (multiplicity of infection) significantly inhibited
      ECV304 proliferation; the difference between uninfected control and Ad-LacZ
      infected control was not significant. In contrast, there was no significant
      difference in the proliferation of MDA-MB-231 among all the treatments. In
      addition, the Ad-K5 at 100 MOI inhibited the differentiation and tube formation
      of ECV304 on ECMatrix gel. These results suggested that the recombinant
      replication-defective Adenovirus expressing human plasminogen kringle 5 inhibited
      the proliferation, differentiation and tube formation of ECV304 and had no effect
      on the proliferation of MDA-MB-231. Adenovirus mediated human plasminogen kringle
      5 gene therapy may be a potential treatment of cancer through angiogenesis
      inhibition.

PMID- 15966327
TI  - [Primary targeting of functional regions involved in transcriptional regulation
      on watermelon fruit-specific promoter WSP].
AB  - Fruit ripening is associated with a number of physiological and biochemical
      changes. They include degradation of chlorophyll, synthesis of flavor compounds,
      carotenoid biosynthesis, conversion of starch to sugars, cell wall solublisation
      and fruit softening. These changes are brought about by the expression of
      specific genes. People are interested in the molecular mechanism involved in the
      regulation of gene transcription during fruit ripening. Many fruit-specific
      promoters such as PG, E4, E8, and 2A11 have been characterized and shown to
      direct ripening-specific expression of reporter genes. AGPase plays the key role
      in catalyzing the biosynthesis of starch in plants. It is a heterotetrameric
      enzyme with two small subunits and two large subunits, which are encoded by
      different genes. In higher plants, small subunits are highly conserved among
      plant species and expressed in all tissues. And the large subunits are present at
      multiple isoforms and expressed in a tissue-specific pattern. In fruits, the
      expression pattern of the large subunits varies with plant species. That made it
      important to study the transcriptional regulation of the large subunits of AGPase
      in different plant species. Northern-blot analysis indicates in watermelon, an
      isoform of the large subunits Wml1 expressed specifically in fruits, not in
      leaves. The 5' flanking region of Wml1, which covers 1573bp, has been isolated
      through the method of uneven PCR. And transient expression assay has shown that
      the 1573bp (named WSP) can direct fruit-specific expression of GUS gene. Our goal
      in this study was to scan the promoter region for main regulatory regions
      involved in fruit-specific expression. A chimaeric gene was constructed
      containing the WSP promoter, the beta-glucuronidase (GUS) structural sequence as
      a reporter gene and the nopaline synthase polyadenylation site (NOS-ter). The
      plasmid pSPA was digested with Hind III + Hinc II and promoter fragment of 1573bp
      (from 180bp to 1752bp) was cut out and cloned into Sma I sites of pBluescript SK(
      ), to produce pBSPA-16. The same insert was then cut out with Hind III + BamH I,
      and ligated with transient expression vector pBI426 digested by HindIII + Bgl II
      to produce pISPA-16. Three 5'-end deletions of the promoter were obtained and
      fused to GUS gene in plant transient expression vector pBI426: the 1201bp
      fragment (from 551bp to 1752bp) was generated by digestion of pBSPA-16 with BamH
      I + SnaB I, the 898bp fragment (from 854bp to 1752bp) by BamH I + EcoRV. Both
      fragments were ligated with pBluescript SK(-) digested by BamH I + Sma I, to
      produce pBSPA-12 and pBS-PA-9. The inserts were cut out with HindmIII + BamH I
      and ligated with pBI426 digested by Hind III + Bgl II, to produce pISPA-12 and
      pISPA-9. The 795bp fragment (from 957bp to 1752bp) was generated by digestion of
      pSPA with Hinc II + EcoR I, promoter fragment was cut out and cloned into Sma I
      sites of pBluescript SK(-), to produce pBSPA-8. The same insert were cut out with
      Hind III + BamH I, and ligated with transient expression vector pBI426 digested
      by Hind III + Bgl II. The 1573bp fragment and three 5'-end deletions were
      delivered into watermelon leaf, stem, flower and fruit of different development
      stages (5, 10, 20 days after pollination) via particle bombardment using a
      biolistic PDS-1000/He particle gun. Bombardment parameters were as follows: a
      helium pressure of 1200 psi, vacuum of 91432.23Pa, 7 cm between the stopping
      screen and the plate. Histochemical assay were done on all the tissues bombarded
      after incubation for 2 days. The 1573bp fragment had the strongest promoter
      activity, and can induce GUS expression in fruits of 5 and 20 days after anthesis
      and flowers, but not in fruits of 10 days after anthesis, leaves and stems.
      Fragments of 1201bp and 898bp can induce GUS expression only in fruits of 20 days
      after anthesis, and with lower expression levels than 1573bp. Fragment of 795bp
      was not able to direct GUS expression in any of the tissues bombarded (data not
      shown). It can be concluded that of the 1573bp, 1201 bp, 898bp Wml1 5'flanking
      regions include the necessary information directing fruit-specific expression.
      Deletion from 180bp to 551bp doesn't affect the fruit-specificity of the
      promoter, but lowered the expression level. There may be some cis-acting elements
      located in this region, which can enhance external gene expression in later
      stages of fruit development. Deletion from 854bp and 958bp led to loss of GUS
      expression. This region includes the necessary information needed for gene
      expression as well as the regulatory elements for fruit-specific transcription.

PMID- 15966326
TI  - [Fermentation and purification of recombinant alpha-galactosidase from Pichia
      pastoris].
AB  - In order to obtain an adequate supply of alpha-galactosidase for research and
      practical use, the fermentation, purification and identification of the
      recombinant coffee bean a-galactosidase were carried out. Baffled flasks
      containing 100mL BMGY were inoculated with the pPIC9K-Gal/GS115 strain and
      allowed to grow at 30 degrees C, 250- 300r/min until a maximum optical density at
      600nm (OD600) between 2.0 to 6.0 was attained. Entire 400 mL seed culture was
      transferred aseptically to the 5-liter fermenter, which contained 4 liter
      sterilized basal salts medium and 4% glycerol. The batch culture grew at 30
      degrees C, pH 5.0 until the glycerol was completely consumed, and a glycerol feed
      was initiated to increase the cell biomass prior to induction with methanol. The
      culture was centrifuged at 8000 x g and the supernatant was collected. Following
      ultrafiltration, the retentate was balanced in 20 mmol/L sodium formicate buffer,
      pH 3.8 and loaded onto a cation-exchange column, HiTrap SP. The column was washed
      with the same buffer and bound proteins were eluted with 1 mol/L NaCl. The
      fractions containing recombinant a-galactosidase were pooled and concentrated
      with PEG20 000. Subsequently, the biochemical properties of the enzyme were
      determined with typical methods. At last, the fresh human blood A and B
      erythrocytes were incubated with the purified alpha-galactosidase at 26 degrees C
      for 2 4 hours. Hemagglutinins were assayed by the standard method. After an
      elapsed fermentation times (EFT) of 18h, the fed-batch phase was initiated to
      increase the cell biomass. A cellular yield of nearly 200 g/liter wet cells was
      achieved when induction was initiated. 72h later, the alpha-galactosidase
      activity against artificial substrate PNPG (PNP-alpha-galactopyranoside) achieved
      36 000u per liter culture. The crude fementation supernatant contained few
      impurities as detected by SDS-PAGE. The supernatant was purified by cation
      exchange chromatography, the target alpha-galactosidase was eluted with 40%
      1mol/L NaCl and showed a 41kD band on SDS-PAGE. After concentration, the final
      recovery was about 41%. The Michaelis constant of the recombinant alpha
      galactosidase was determined as 0.275 mmol/L, which slightly lower than the
      nature enzyme and suggested a higher affinity with specific substrate. When human
      blood type B erythrocytes pretreated with 100u/mL recombinant alpha-galactosidase
      reacted with bood type B antiserum, no hemagglutination occurred. This suggested
      that the B antigens had been removed by the enzyme successfully. These results
      demonstrated that the recombinant alpha-galactosidase could be produced in
      largescale and made it possible to explore the application of alpha-galactosidase
      in more fields.

PMID- 15966328
TI  - [Overexpression of Penicillium expansum lipase gene in Pichia pastoris].
AB  - The alkaline lipase gene of Penicillium expansum (PEL) was coloned into the yeast
      integrative plasmid pPIC3.5K, which was then transformed into His4 mutant yeast
      GS115. Recombinant Pichia strains were obtained by minimal olive oil-methanol
      plates screening and confirmed by PCR. The expression producus of PEL gene was
      analysis by SDS-PAGE and olive oil plate, the result indicated that PEL gene was
      functionally overexpressed in Pichia pastoris and up to 95% of the secreted
      protein. Recombinant lipase had a molecular mass of 28kD, showing a range similar
      to that of PEL, could hydrolyze olive oil and formed clear halos in the olive oil
      plates. Four different strategies (different media, pH, glycerol and methanol
      concentration) were applied to optimize the cultivation conditions, the activity
      of lipase was up to 260 u/mL under the optimal cultivation conditions. It is
      pointed out that the absence of the expensive biotin and yeast nitrogen base in
      the medium increased the lipase production. The possible reason of this result is
      absence of yeast nitrogen base increased the medium pH during cultivation, and
      PEL shows a higher stability at this condition. The lipase activity of the
      supernatant from the culture grown at pH 7 was higher than the one from the
      culture in the same medium at pH 6.0 is due to the pH stability of PEL too. The
      results also showed that the methanol and glycerol concentration had a marked
      effect on the production of lipase.

PMID- 15966329
TI  - [Studies on immobilized cellobiase].
AB  - Cellulosic material is the most abundant renewable carbon source in the world.
      Cellulose may be hydrolyzed using cellulase to produce glucose, which can be used
      for production of ethanol, organic acids, and other chemicals. Cellulase is a
      complex enzyme containing endoglucanase (EC 3.2.1.4), exoglucanase (EC 3.2.1.91)
      and cellobiase (EC 3.2.1.21). The hydrolysis of natural cellulose to glucose
      depends on the synergism of these three components. The mostly used cellulase
      produced by Trichoderma reesei has high activity of endoglucanase and
      exoglucanase, but the activity of cellobiase is relatively low. Therefore,
      improving the activity of cellobiase in cellulase reaction system is the key to
      enhance the sacchrification yield of cellulosic resources. Aspergillus niger
      LORRE 012 was a high productivity strain for cellobiase production. It was found
      that the spores of this strain were rich in cellobiase. In this work, the
      cellobiase was immobilized efficiently by simply entrapping the spores into
      calcium alginate gels instead of immobilizing the pure cellobiase proteins. The
      immobilized cellobiase was quite stable, and its half-life was 38 days under pH
      4.8, 50 degrees C. The thermal stability of the immobilized cellobiase was
      improved, and it was stable below 70 degrees C. The suitable pH range of the
      immobilized cellobiase was pH 3.0 - 5.0, with the optimal pH value 4.8. The Km
      and Vmax value of the immobilized cellobiase were 6.01 mmol/L and 7.06 mmol/min x
      L, respectively. In repeated batch hydrolysis processes, 50 mL of substrate (10
      g/L cellobiose) and 10 mL of immobilized beads containing cellobiase were added
      into a 150 ml flask. After reacting at pH 4.8, 50 degrees C for several hours,
      the hydrolysate was harvested for assay, and the immobilized beads were used for
      the next batch hydrolysis with the fresh substrate. This process was repeated,
      and the yield of enzymatic hydrolysis kept higher than 97% during 10 batches. The
      continuous hydrolysis process was carried out in a column reactor (inside
      diameter 2.8 cm, inside height 40 cm) packed with the immobilized beads. Using 10
      g/L cellobiose as substrate, the hydrolysis yield reached 98% under 0.4 h (-1)
      dilution rate and pH 4.8, 50 degrees C. After corncob was treated by 1% dilute
      acid, the cellulosic residue (100 g/L) was used as substrate, and hydrolyzed by
      the cellulase (15 IFPU/g substrate) from Trichoderma reesei, at pH 4.8, 50
      degrees C for 48 h. The concentration of reducing sugar in the hydrolysate was
      only 48.50 g/L (hydrolysis yield 69.5%). When the hydrolysate was further treated
      by the immobilized cellobiase, the cellobiose was hydrolyzed into glucose, and
      the feedback inhibition caused by the cellobiose accumulation disappeared
      sharply. By the synergism of immobilized cellobiase and the cellulase from T.
      reesei left in the hydrolysate, other oligosaccharides were mostly converted to
      monosaccharides. At 48 h, the reducing sugar concentration was increased to 58.78
      g/L, the hydrolysis yield of the corncob residue was improved to 84.2%, and the
      ratio of the glucose in the total reducing sugar was increased from 53.6% to
      89.5%. The reducing sugars converted from corncob could be used further in the
      fermentation of valuable industrial products. This research results were
      meaningful in the conversion and utilization of renewable biomass.

PMID- 15966330
TI  - [The action of S1 nuclease and a cloning strategy for microcircular DNAs].
AB  - S1 nuclease (from Aspergillus oryzae) is a specific enzyme to degrade single
      stranded DNA or RNA molecules. It has been reported to be able to convert
      superhelical circular DNA molecules into open circle or linear forms under
      certain conditions, but this function has not been well explored. In order to use
      the action of S1 nuclease to linearize circular DNA and develop a novel way of
      cloning microcircular DNAs, the pUC19 was used to investigate the relationship
      between the linearization efficiency of S1 nuclease and the amount of enzyme
      used. By this way the optimal conditions for linearization of circular DNAs by S1
      nuclease would be determined. 0.3u to 17u S1 nuclease per 100ng pUC19 DNA was
      added into a 25 microL system, respectively, to perform the reaction. The
      effectiveness of enzyme digestion was realized by electrophoresis in a 1.2%
      agarose gel. The results showed that along with the increase in enzyme amount
      from 0.3u to 17u a gradual decrease in the superhelical form, a gradual increase
      in the linear form and then in the circular form was obvious. The conversion from
      superhelical form to linear and circular form was directly related to the enzyme
      amount used. A higher proportion of linear DNA molecules was achieved by using 5
      to 17u S1 nuclease per 100ng DNA. Besides, electrophoretic mobility of the S1
      nuclease-linearized pUC19 was the same as that of the linear form produced by
      restriction enzyme digestion. According to the result of phiX174 digested by S1
      nuclease it has been proposed that the enzyme cleaves first randomly on one site
      of one strand, thus converting the superhelical molecules into open circle form,
      and then on the same site of the complementary strand to produce the linear form.
      Therefore, the S1 nuclease-linearized DNA molecules are intact in the sense of
      their length and can be used for cloning. The plasmid-like DNA pC3 from cucumber
      mitochondria is a double stranded circular DNA molecule with about 550bp and the
      smallest known plasmid-like DNA in eukaryotic mitochondria. Many attempts have
      been made to linearize the molecule by using restriction enzymes but failed.
      Therefore, S1 nuclease was used to linearize pC3 based on the results obtained
      with pUC19. The linearized pC3 DNA molecules formed a very sharp band in a 2.5%
      agarose gel after electrophoresis. They were then recovered from the gel, added
      an "A" tail and ligated with T-vector. After transformation into E. coli JM109
      cells, the positive clones were, screened by the blue-white selection. The insert
      was then cut using restriction enzymes EcoRI and Pst I. The result of
      electrophoresis shows that the electrophoretic mobility of the insert is just the
      same as that predicted. A 32 P-labled probe was synthesized using pC3 as the
      template and Southern blot analysis was carried out. The result shows that the
      inserted DNA is hybridized to the probe, which indicates that the cloned DNA
      fragment is from pC3. The sequence information of the insert shows that the
      plasmid-like DNA pC3 was 537bp in length. The nucleotide sequence was deposited
      in the GenBank (the accession number is AF522195).

PMID- 15966331
TI  - [Advances in analysis techniques of phosphoproteome].
AB  - In eukaryotes protein phosphorytion is a key event. By reversible protein
      phosphorylation eukaryotes control many cellular processes including signal
      transduction, gene expression, the cell cycle etc. Phosphoproteomics involves
      identification of phosphoproteins and phosphopeptides, localization of the exact
      residues that are phosphorylated and quantitation of phosphorylation. Because
      protein phosphorylation is a dynamic process, and it is present at low abundance
      within cells, and the phosphorylated sites on proteins might vary, and mass
      spectrometry (MS) signals from phosphopeptides are usually suppressed etc., so
      phosphoprotein analysis have more difficulties than nonphosphoprotein. In this
      article, we outline several analysis techniques for separation, identification
      and quantitation of phosphorylated proteins and peptides, and discuss the
      progress in these techniques. At present, MS is still an essential core
      identification technology for phosphoproteomic studies, To search better
      enrichment strategies are the main challenges in this rapidly evolving field. A
      major goal of quantitative proteomics is precise quantification and
      identification of proteins in complex mixtures. A common method for quantitative
      proteome analysis is the stable isotope labeling method. Today there is no single
      method that supersedes all others techniques for Phosphoproteomic studies. With
      continued development of sample preparation techniques and instrumentation, it
      should be possible to perform a global analysis of protein phosphorylation.

PMID- 15966332
TI  - [Protein splicing and its application].
AB  - Protein splicing is a newly discovered posttranslational editing process that
      removes an internal protein fragment from the protein precursor. During the
      splicing process the internal protein fragment, intein, triggered the self
      excision from the precursor protein and the concomitant ligation of the flanking
      protein fragments, exteins. The self-catalysis requires neither auxiliary enzymes
      nor cofactors and only involves four intramolecular reactions. A number of key
      catalytic residues in inteins and flanking fragments have been identified, which
      led to the development of the protein splicing process as a protein engineering
      tool. Controllable cleavage of the peptide bond at either the N or the C terminus
      of an intein has allowed the design of novel strategies for manipulation of
      protein and peptides. Affinity purification of recombinant proteins can be
      facilitated by fusion the target protein with an intein. The fusion also creates
      C-terminal thioester, which expands the scope of chemical ligation in protein.
      Inteins can be engineered in a "split and inverted" configuration to form a
      cyclic polypeptide consisting of the sequence linking two intein subdomains. This
      article summarizes the recent advance in the mechanism of protein splicing and
      its applications in protein purification, protein ligation and protein
      cyclization.

PMID- 15966333
TI  - [Prognostic markers in ovarian carcinoma--retrospective study].
AB  - Ovarian carcinoma is one of the most common cancers in women. The high mortality
      is due mostly to the fact that the tumour is frequently diagnosed in advanced
      stages. The aim of our study was to find immunohistochemically detectable
      significant prognostic markers for invasive ovarian carcinoma. There were two
      areas of research: the expression of hormonal receptors by tumour cells, and the
      examination of proliferation activity of the tumour cell by means of antibody Ki
      67. Tumour samples from 96 patients with carcinoma of ovary were evaluated (age
      27-82 years, mean 55.2 years). Size of residual tumour (p = 0.00002), FIGO stage
      (p = 0.001), age (p = 0.018), expression of progesterone receptors (p = 0.004),
      coexpression of steroid receptors (p = 0.039), proliferation activity of the
      tumour cell (p = 0.04), and chemotherapy (p = 0.018) were significant predictors
      of survival in univariate analysis. Borderline significance was found in other
      evaluated parameters: grade (p = 0.063) and histology of carcinoma (p = 0.085).
      Expression of estrogen receptors and radiotherapy were not correlated to survival
      in univariate analysis. Multivariate analysis revealed that only clinical
      parameters were significant prognostic factors: size of residual tumor (p <
      0.0000), chemotherapy (p = 0.0009), radiotherapy (p = 0.0097), and age (p =
      0.0048).

PMID- 15966334
TI  - [What is your diagnosis? Answer: Ependymoma, cellular and clear cell variant].

PMID- 15966335
TI  - [Comment on the new WHO classification of salivary gland tumors].

PMID- 15966336
TI  - Ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and
      synchronous cervical squamous carcinoma.
AB  - Solid mural nodule within a mucinous cystic ovarian tumor occurs more often than
      generally presumed. One especially interesting case involving coincidental
      cervical carcinoma is presented. A 38-year-old woman underwent exploratory
      laparotomy for a right ovarian tumor. After ovarian malignancy had been diagnosed
      from frozen section, the bilateral salpingo-oophorectomy and hysterectomy was
      performed. The tumor had a unilocular cystic cavity and a mural nodule. The
      nodule showed undifferentiated carcinomatous features. The immunohistochemical
      examination revealed atypical cells in the nodule which were positive for
      cytokeratin, CEA, and vimentine, establishing its anaplastic nature. A
      synchronous cervical invasive squamous carcinoma was documented. The patient was
      treated with chemotherapy and radiotherapy. Currently, at 15 postoperative
      months, she is well and free of disease. The occurrence of ovarian mucinous
      cystadenocarcinoma with mural nodule of anaplastic carcinoma and cervical
      squamous cell carcinoma is evidently very uncommon, because we have not found a
      similar case in the literature.

PMID- 15966337
TI  - [Lymphoepithelial cyst of the thyroid coexistent with amyloid goiter].
AB  - A case of amyloid goiter in a 73-year-old man with systemic amyloidosis
      complicating long lasting rheumatoid arthritis is reported. The thyroid gland was
      massively infiltrated with amyloid and contained foci of fat tissue and
      epithelial solid cell nests. Incidentally, a cyst lined by squamous epithelium,
      with small amount of lymphocytes in the subepithelial stroma was found. This cyst
      fulfilled the criteria for the diagnosis of a lymphoepithelial cyst presumably of
      branchiogenic origin. The herein described case of simultaneous occurrence of
      branchiogenic cyst and amyloid goiter represents, to our best knowledge, a unique
      coexistence of these two entities. The possible relationship between these
      lesions and their differential diagnosis is discussed.

PMID- 15966339
TI  - Extending scientific knowledge through the study of sport and exercise
      psychology.

PMID- 15966340
TI  - A three-dimensional examination of the planar nature of the golf swing.
AB  - Previous planar models of the downswing in golf have suggested that upper limb
      segments (left shoulder girdle and left arm) move in a consistent fixed plane and
      that the clubhead also moves only in this plane. This study sought to examine
      these assumptions. Three-dimensional kinematic analysis of seven right-handed
      golfers of various abilities (handicap 0- 15) was used to define a plane (named
      the left-arm plane) containing the 7th cervical vertebra, left shoulder and left
      wrist. We found that the angles of this plane to the reference horizontal z axis
      and target line axis (parallel to the reference x axis) were not consistent. The
      angle to the horizontal z axis varied from a mean of 133 degrees (s = 1 degrees)
      at the start of the downswing to 102 degrees (s = 4 degrees) at impact,
      suggesting a "steepening" of the left-arm plane. The angle of the plane to the
      target line changed from - 9 degrees (s = 16 degrees) to 5 degrees (s = 15
      degrees) during the same period, showing anticlockwise (from above) rotation,
      although there was large inter-individual variation. The distance of the clubhead
      from the left-arm plane was 0.019 m (s = 0.280 m) at the start at the downswing
      and 0.291 m (s = 0.077 m) at impact, showing that the clubhead did not lie in the
      same plane as the body segments. We conclude that the left arm and shoulder
      girdle do not move in a consistent plane throughout the downswing, and that the
      clubhead does not move in this plane. Previous models of the downswing in golf
      may therefore be incorrect, and more complex (but realistic) simulations should
      be performed.

PMID- 15966341
TI  - Nutritional intake in soccer players of different ages.
AB  - The purpose of this study was to evaluate the dietary practices of soccer players
      of different ages. The diets of the members of four soccer teams (mean ages of
      14.0, 15.0, 16.6 and 20.9 years, respectively) were examined. Our results show
      that the caloric intake per kilogram of body mass was significantly higher among
      the youngest players when compared with the adult players (P < 0.05). The
      contribution of carbohydrates to total energy intake was lower than that
      recommended for athletes. This contribution decreased with age from 47.4% of
      total energy intake for the 14-year-olds to 44.6% for the adult players. No
      significant differences in protein or total fat intake were detected among the
      teams examined. Overall, our results show that the nutritional intake of the
      soccer players was not optimal, and that this intake was poorer among the adult
      players than among the adolescents. On the basis of our results, we recommended
      that nutritional education should be given to soccer players at an early age and
      should continue throughout adolescence, not only with a view to improving
      performance but also to promoting more healthy dietary practices in the long
      term.

PMID- 15966342
TI  - The acute effects of resistance exercise on the main determinants of blood
      rheology.
AB  - The aim of this study was to examine short-term changes in blood rheological
      variables after a single bout of resistance exercise. Twenty-one healthy males
      completed three sets of 5 - 7 repetitions of six exercises at an intensity
      corresponding to 80% of one-repetition maximum (1-RM). The average duration of
      the exercise bout was 35 min. Venous blood samples were obtained before exercise,
      immediately after exercise and after 30 min of recovery and analysed for lactate,
      red blood cell count, haematocrit, haemoglobin, plasma viscosity, fibrinogen,
      total protein and albumin concentration. Plasma volume decreased 10.1% following
      resistance exercise. This occurred in parallel with an increase of 5.6%, 5.4% and
      6.2% in red blood cell count, haemoglobin and haematocrit; respectively. Plasma
      viscosity increased from 1.55 +/- 0.01 to 1.64 +/- 0.01 mPa s immediately after
      resistance exercise before decreasing to 1.57 +/- 0.01 mPa s at the end of the
      recovery period. Similarly, fibrinogen, albumin and total protein increased
      significantly following resistance exercise. However, the rises in all these
      rheological parameters were transient and returned to pre-exercise values by the
      end of recovery. We conclude that a single session of heavy resistance exercise
      performed by normal healthy individuals alters blood rheological variables and
      that these changes are transient and could be attributed to exercise-induced
      haemoconcentration.

PMID- 15966343
TI  - A single session of resistance exercise does not reduce postprandial lipaemia.
AB  - This study investigated the effect of a single session of resistance exercise on
      postprandial lipaemia. Eleven healthy normolipidaemic men with a mean age of 23
      (standard error = 1.4) years performed two trials at least 1 week apart in a
      counterbalanced randomized design. In each trial, participants consumed a test
      meal (1.2 g fat, 1.1 g carbohydrate, 0.2 g protein and 68 kJ x kg(-1) body mass)
      between 08.00 and 09.00 h following a 12 h fast. The afternoon before one trial,
      the participants performed an 88 min bout of resistance exercise. Before the
      other trial, the participants were inactive (control trial). Resistance exercise
      was performed using free weights and included four sets of 10 repetitions of each
      of 11 exercises. Sets were performed at 80% of 10-repetition maximum with a 2 min
      work and rest interval. Venous blood samples were obtained in the fasted state
      and at intervals for 6 h postprandially. Fasting plasma triacylglycerol (TAG)
      concentration did not differ significantly between control (1.03 +/- 0.13 mmol x
      l(-1)) and exercise (0.94 +/- 0.09 mmol x l(-1)) trials (mean +/- standard
      error). Similarly, the 6 h total area under the plasma TAG concentration versus
      time curve did not differ significantly between the control (9.84 +/- 1.40 mmol
      l(-1) x 6 h(-1)) and exercise (9.38 +/- 1.12 mmol x l(-1) x 6 h(-1)) trials.
      These findings suggest that a single session of resistance exercise does not
      reduce postprandial lipaemia.

PMID- 15966344
TI  - An investigation of home advantage and other factors affecting outcomes in
      English one-day cricket matches.
AB  - We examined the factors affecting the outcome of cricket matches played in the
      English one-day county cricket league. In particular, we focused on the home
      field effect and the importance of winning the pre-match toss of a coin to
      determine a team's strategic decision to bat first or second. A home-field effect
      appeared to be confirmed in that home teams won 57% of all matches with a
      win/loss result. A logistical regression model was used, with the outcome
      variable defined in terms of a home team win/loss. We found that while winning
      the toss is an important aspect of a one-day cricket match, other factors tend to
      dominate in determining the result, especially team quality and match importance
      for the home and away teams in the overall league context. Our results also
      indicate, not surprisingly given the nature of cricket attendance and spectating,
      that the crowd effect is largely insignificant. The results of our study do not
      support any rule changes requiring the abandonment of the coin toss to determine
      batting order.

PMID- 15966345
TI  - Physical activity and school recess time: differences between the sexes and the
      relationship between children's playground physical activity and habitual
      physical activity.
AB  - The aims of this study were: (1) to observe participation in moderate-to-vigorous
      physical activity (MVPA) during school recess periods; (2) to determine the
      relative importance of physical activity during recesses to overall daily
      physical activity; and (3) to examine differences in physical activity between
      the sexes during unstructured recess periods. The participants were 22 school
      children (10 boys, 12 girls) aged 8 - 10 years (mean = 8.9, s = 0.7) in the third
      and fourth grades. Daily totals for the physical activity variables were
      calculated by summing the values for each hour of 14 h of physical activity
      measurements (08:00 to 22:00 h). Recess times (minutes) were as follows: morning
      10:30 to 11:00 h and afternoon 15:30 to 16:00 h. We did not differences between
      boys and girls in daily total accelerometer counts or the overall time spent in
      MVPA. However, girls were significantly (P < 0.05) more involved (38%) in MVPA
      during recess time than boys (31%). Participation in MVPA during recess
      contributes significantly more (P < 0.05) for girls (19%) than boys (15%) to the
      total amount of physical activity suggested by international health-related
      physical activity guidelines, while the percentage of time engaged in MVPA during
      recess time at school accounts for a small amount of the daily MVPA (6% for boys
      and 8% for girls). The results of this study suggest that school recess time is
      an important setting to promote MVPA and contributes to daily physical activity
      in young children, especially in girls.

PMID- 15966346
TI  - Endurance training adherence in elite junior netball athletes: a test of the
      theory of planned behaviour and a revised theory of planned behaviour.
AB  - This study examined the utility of Ajzen's (1985) theory of planned behaviour and
      Maddux's (1993) revised theory of planned behaviour to predict endurance training
      intentions and adherence of elite junior netball athletes. One hundred and
      fifteen athletes from the England Netball World Class Start Programme were
      assessed on constructs central to the predictions of the two theories. Adherence
      to a recommended endurance training programme was recorded in self-report diaries
      across a 9-week period. Validity for the diaries was supported by significant
      correlations (P < 0.001) with recalls across 7 days and 9 weeks. Adherence was
      moderate and variable between athletes (mean = 66.05, s = 25.75%). Two separate
      path analyses were conducted to examine the predictions of the theories. Goodness
      of-fit indices suggested acceptable fit of the data to the models. Analyses
      showed that attitude towards the new behaviour, subjective norms and perceived
      behavioural control predicted training intentions. The relationship between
      intention and adherence was weak. The present results suggest that the constructs
      of the theory of planned behaviour offer some insight into the explanation of
      intentions to follow an endurance training programme. Constructs unique to the
      revised theory of planned behaviour did not significantly predict training
      intentions or behaviour. Implications for practitioners working with team sport
      performers are provided.

PMID- 15966347
TI  - Prediction of energy expenditure from heart rate monitoring during submaximal
      exercise.
AB  - The aims of this study were to quantify the effects of factors such as mode of
      exercise, body composition and training on the relationship between heart rate
      and physical activity energy expenditure (measured in kJ x min(-1)) and to
      develop prediction equations for energy expenditure from heart rate. Regularly
      exercising individuals (n = 115; age 18-45 years, body mass 47-120 kg) underwent
      a test for maximal oxygen uptake (VO2max test), using incremental protocols on
      either a cycle ergometer or treadmill; VO2max ranged from 27 to 81 ml x kg(-1) x
      min(-1). The participants then completed three steady-state exercise stages on
      either the treadmill (10 min) or the cycle ergometer (15 min) at 35%, 62% and 80%
      of VO2max, corresponding to 57%, 77% and 90% of maximal heart rate. Heart rate
      and respiratory exchange ratio data were collected during each stage. A mixed
      model analysis identified gender, heart rate, weight, V2max and age as factors
      that best predicted the relationship between heart rate and energy expenditure.
      The model (with the highest likelihood ratio) was used to estimate energy
      expenditure. The correlation coefficient (r) between the measured and estimated
      energy expenditure was 0.913. The model therefore accounted for 83.3% (R2) of the
      variance in energy expenditure in this sample. Because a measure of fitness, such
      as VO2max, is not always available, a model without VO2max included was also
      fitted. The correlation coefficient between the measured energy expenditure and
      estimates from the mixed model without VO2max was 0.857. It follows that the
      model without a fitness measure accounted for 73.4% of the variance in energy
      expenditure in this sample. Based on these results, we conclude that it is
      possible to estimate physical activity energy expenditure from heart rate in a
      group of individuals with a great deal of accuracy, after adjusting for age,
      gender, body mass and fitness.

PMID- 15966348
TI  - Energy system contribution to 400-metre and 800-metre track running.
AB  - As a wide range of values has been reported for the relative energetics of 400-m
      and 800-m track running events, this study aimed to quantify the respective
      aerobic and anaerobic energy contributions to these events during track running.
      Sixteen trained 400-m (11 males, 5 females) and 11 trained 800-m (9 males, 2
      females) athletes participated in this study. The participants performed (on
      separate days) a laboratory graded exercsie test and multiple race time-trials.
      The relative energy system contribution was calculated by multiple methods based
      upon measures of race VO2, accumulated oxygen deficit (AOD), blood lactate and
      estimated phosphocreatine degradation (lactate/PCr). The aerobic/anaerobic energy
      system contribution (AOD method) to the 400-m event was calculated as 41/59%
      (male) and 45/55% (female). For the 800-m event, an increased aerobic involvement
      was noted with a 60/40% (male) and 70/30% (female) respective contribution.
      Significant (P < 0.05) negative correlations were noted between race performance
      and anaerobic energy system involvement (lactate/PCr) for the male 800-m and
      female 400-m events (r = - 0.77 and - 0.87 respectively). These track running
      data compare well with previous estimates of the relative energy system
      contributions to the 400-m and 800-m events. Additionally, the relative
      importance and speed of interaction of the respective metabolic pathways has
      implications to training for these events.

PMID- 15966349
TI  - A new index of flat breaststroke propulsion: a comparison of elite men and women.
AB  - This study examined arm and leg coordination and propulsion during the flat
      breaststroke in nine elite male and eight elite female swimmers over three race
      paces (200 m, 100 m and 50 m). Coordination was expressed using four temporal
      gaps (T1, T2, T3, T4), which described the continuity between the propulsive
      phases of the limbs, as recorded on a video device (50 Hz). Glide duration was
      denoted T1, the time between the beginning of arm and leg recovery was denoted
      T2, the time between the end of arm and the leg recovery was denoted T3, and the
      time between 90 degrees of flexion during arm recovery and 90 degrees during leg
      recovery was denoted T4. Using these temporal gaps, four stroke phases
      (propulsion, glide, recovery and leg insweep) could be followed over a complete
      arm and leg stroke. The total duration of arm and leg propulsion was assessed by
      a new index of flat breaststroke propulsion (IFBP). Velocity, stroke rate and
      stroke length were also calculated for each pace. The elite swimmers showed short
      T2, T3 and T4; moreover, T1 decreased when the pace increased. Expertise in the
      flat breaststroke was thus characterized by synchronized arm and leg recoveries
      and increased continuity in the arm and leg propulsions with increasing velocity.
      Differences between the sexes in the spatio-temporal parameters were possibly due
      to anthropometric differences (the men were heavier, older and taller than the
      women) and different motor organization linked to arm and leg coordination
      (shorter T3, body glide and body recovery, and greater body propulsion and higher
      IFBP in the men). The men's propulsive actions showed greater continuity,
      particularly in the sprint. The best men adopted a superposition coordination and
      thus had the ability to overcome very great active drag. Temporal gap measurement
      and the IFBP are practical indicators of arm and leg coordination and propulsion
      that can be exploited by coaches and swimmers to increase the continuity between
      propulsive actions during the flat breaststroke.

PMID- 15966350
TI  - Diurnal variation in cycling performance: influence of warm-up.
AB  - We examined the effects of time of day on a cycling time trial with and without a
      prolonged warm-up, among cyclists who tended towards being high in "morningness".
      Eight male cyclists (mean +/- s: age = 24.9 +/- 3.5 years, peak power output =
      319 +/- 34 W, chronotype = 39 +/- 6 units) completed a 16.1-km time trial without
      a substantial warm-up at both 07:30 and 17:30 h. The time trial was also
      completed at both times of day after a 25-min warm-up at 60% of peak power. Power
      output, heart rate, intra-aural temperature and category ratings of perceived
      exertion (CR-10) were measured throughout the time trial. Post-test blood lactate
      concentration was also recorded. Warm-up generally improved time trial
      performance at both times of day (95% CI for improvement = 0 to 30 s), but mean
      cycling time was still significantly slower at 07:30 h than at 17:30 h after the
      warm-up (95% CI for difference = 33 to 66 s). Intra-aural temperature increased
      as the time trial progressed (P < 0.0005) and was significantly higher throughout
      the time trials at 17:30 h (P = 0.001), irrespective of whether the cyclists
      performed a warm-up or not. Blood lactate concentration after the time trial was
      lowest at 07:30 h without a warm-up (P = 0.02). No effects of time of day or warm
      up were found for CR-10 or heart rate responses during the time trial. These
      results suggest that 16.1-km cycling performance is worse in the morning than in
      the afternoon, even with athletes who tend towards 'morningness', and who perform
      a vigorous 25-min warm-up. Diurnal variation in cycling performance is,
      therefore, relatively robust to some external and behavioural factors.

PMID- 15966351
TI  - New financial year, new pension headaches.

PMID- 15966352
TI  - Encouraging best practice in infection control.

PMID- 15966353
TI  - Evidence-based strategies for the use of oral nutritional supplements.
AB  - Prescribable oral nutritional supplements are commonly used as a method of
      nutritional support in the prevention and treatment of malnutrition in adults.
      There is growing evidence to suggest that when used appropriately in treatment
      plans, individuals receiving them will benefit from functional and clinical
      improvements. The use of supplements in the community has increased over the last
      decade and questions about the increasing costs and efficacy of the products are
      often raised within health-care communities. The development of guidelines and
      protocols for the use of supplements in the community that are based on evidence
      of need and indicate a clear pathway of care, together with intended benefit,
      should help to address the issues of costly, inappropriate prescribing.

PMID- 15966354
TI  - A primary falls prevention programme for older people in Hong Kong.
AB  - This study describes the development and implementation of a large-scale primary
      fall and fracture prevention programme in Hong Kong and its effect on increasing
      the awareness and knowledge of fall and fracture prevention among older people.
      The effect of promotion of community participation is also investigated in the
      implementation of this primary prevention programme. The programme includes
      educational seminars, a train-the-trainers programme and a staff training
      programme. The effect of the educational seminars is shown by the increase in the
      knowledge and awareness of fall and fracture prevention among these participants
      (p < 0.01), while that of the train-the-trainers programme and staff-training
      programme is confirmed by the continuous expansion and continuation of the fall
      and fracture prevention programme in the community. The experience from this
      primary prevention programme has given us direction for future implementation of
      a more comprehensive prevention programme in our community.

PMID- 15966355
TI  - Urinary urge incontinence: causes and management strategies.
AB  - Bladder control is a skill most people learn in childhood, so if control is lost
      in adult life the impact can be very significant, particularly on the quality of
      life of the person affected. There are many causes of loss of bladder control,
      ranging from neurological conditions to menopause, as well as certain
      medications. This article discusses urinary urgency and urge incontinence,
      examines its causes and diagnosis, and provides an overview of the nursing
      interventions available to treat the problem.

PMID- 15966356
TI  - Crossing barriers to bring change to the inner city.

PMID- 15966357
TI  - Coronary heart disease: an update on progress of the NSF.
AB  - Coronary heart disease (CHD) is a preventable disease, yet is kills over 100,000
      people a year in the UK. CHD was among the first conditions to be addressed by a
      national service framework (NSF), published in 2000. Five years on, this article
      discusses the key tenets of the NSF that apply to primary care and how they
      should be being implemented, and discusses what else the Government is doing to
      tackle this common and costly condition.

PMID- 15966358
TI  - The importance of recognizing abuse of older people.
AB  - Abuse within families happens far more often than most people would be prepared
      to acknowledge, and can take many forms. Action has been taken by government to
      address issues of child abuse and domestic violence, but abuse of older people
      has until recently been neglected. In this article, the CDNA's elder abuse
      specialist discusses why this is so, and how to identify abuse of older people
      when it happens.

PMID- 15966359
TI  - Health protection and age-related legislation.
AB  - Community children's nurse Debbie James has developed an innovative scheme to
      allow secondary school children to obtain health advice by texting her service
      using mobile phones. As well as general advice about spots and rubella
      immunization, Sister James is also receiving inquiries about children's legal
      rights that also have a health protection purpose, such how old a child has to be
      before owning a pet or have an alcoholic drink. This article looks at how the law
      seeks to protect children by incrementally giving them legal rights as they
      develop to mature adults and how legal awareness can help inform community health
      practitioners' advice to their child clients.

PMID- 15966360
TI  - Staking a claim to manage chronic disease.

PMID- 15966362
TI  - [Diversity of staphylococcal enterotoxins].

PMID- 15966361
TI  - [Study on antigenicity and pathogenicity of mycobacteria].

PMID- 15966363
TI  - [Virulence factors in Streptococcus pyogenes infection].

PMID- 15966364
TI  - [Molecular mechanisms of Salmonella entry into host cells and survival within
      phagocytic cells].

PMID- 15966365
TI  - [Role of peptidoglycan recognition protein family in innate immunity].

PMID- 15966366
TI  - [Understanding of pneumococcal vaccination in patients with chronic respiratory
      diseases].
AB  - Pneumococcal vaccination is still rare in Japan. To evaluate understanding
      concerning the vaccination, we employed a questionnaire answered by patients aged
      over 60 with chronic respiratory diseases from August to October 2002. Only 286
      (18%) of the 1595 patients already knew of the existence of the vaccine, and 999
      (64%) patients wanted to be vaccinated. That season, 717 (43%) patients were
      actually vaccinated. Patients with chronic respiratory failure, those who had
      contracted pulmonary infections in the previous year, those over 70 year-old, and
      male patients tended to be vaccinated. Although elderly and high-risk patients
      are recommended to be vaccinated, the pneumococcal vaccination rates in those
      patients was low. Campaigns for vaccination are needed.

PMID- 15966367
TI  - [Measurement of peak inspiratory flow with asthma: effect of inhaled beta2
      stimulant].
AB  - This study was designed to evaluate peak inspiratory flow (PIF) and peak
      expiratory flow (PEF) in 24 patients with mild asthma. After inhalation of a
      beta2-stimulant (beta2), PIF significantly increased from 173.0 +/- 67.0 (range
      70-300 L/min) to 194.0 +/- 66.7 after 1 minute, and to 199.3 +/- 63.0 after 15
      minutes (p < 0.0025, and p < 0.008, respectively). PEF also significantly
      increased. The previous inhalation of beta2 improved the efficacy of inhalation
      of dry powder. This evidence should be considered in performing patient education
      for effective methods of inhalation.

PMID- 15966368
TI  - [Sucessful treatment by micafungin of pulmonary aspergillosis occurring in an old
      lung abscess].
AB  - A 55-year-old man, who had diabetes from age 46 years old had been treated for a
      lung abscess in the right upper lobe at age 51. He underwent an operation for
      stomach cancer at age 52. When he was 55 years old, a cavity lesion appeared in
      his right upper lobe at the site of the treated lung abscess. Pulmonary
      aspergillosis was diagnosed by bronchial biopsy. In this case, we controlled his
      diabetes and used micafungin which has a mechanism unlike other conventional
      antifungal agents. The shadow decreased and examination of the resected specimen
      showed that the fungus had disappeard. Pulmonary aspergillosis is an important
      mycosis profunda and micafungin seems to be an effective antifungal agent against
      it.

PMID- 15966369
TI  - [A case of sub-acute onset pulmonary sarcoidosis with pulmonary dysfunction].
AB  - A 60-year-old man was admitted to our hospital because of shortness of breath and
      dry cough. Slight pleural thickening was observed on the chest X-ray film and
      chest CT on presenting. Three months later, bilateral hilar lymphadenopathy and
      multiple small nodular shadows were shown in both lung fields by chest CT. Serum
      ACE level and lysozyme levels were higher than normal upper limit. Elevation of
      CRP and left shift of leukocytes were not detected. Restrictive ventilatory
      impairment was shown in the respiratory function test. This case was diagnosed as
      sarcoidosis most probably with histological evidence of epithelioid cell
      granulomas in the lung tissue obtained by transbronchial lung biopsy. After
      prednisolone medication (40 mg per day) was started, symptoms, pulmonary function
      and chest CT findings improved. Our case was considered to be a rare case of
      pulmonary sarcoidosis with subacute onset of symptoms and restrictive pulmonary
      function abnormality which improved smoothly as a result of steroid therapy.

PMID- 15966370
TI  - [A case of pulmonary actinomycosis, who expectorated sulfur granules, caused by
      Actinomyces odontolyticus and Actinomyces meyeri].
AB  - A 51-year-old man complaining of cough and bloody sputum, was admitted to our
      hospital because of antibiotic-resistant chronic pneumonia in the right upper
      lobe. Initially, bronchoscopic examination and sputum culture revealed no
      evidence of malignancy or any specific infection, either pathologically or
      microbiologically. However, pathological examination of a solid body expectorated
      with sputum revealed typical sulfur granules, indicating pulmonary actinomycosis.
      Two actinomyceses named Actinomyces odontolyticus and Actinomyces meyeri were
      detected later. Pulmonary infection caused by these types of actinomyceses is
      rare, and the diagnostic procedure seemed to be unusual.

PMID- 15966371
TI  - [A case of pseudo-meigs syndrome due to ovarian clear cell adenocarcinoma].
AB  - A 59-year-old woman was admitted with dyspnea. A chest X-ray film revealed a
      large amount of pleural effusion at the both sides. No malignant cells were found
      in bilateral pleural effusions. Computed tomography (CT) of the abdomen showed a
      huge mass of the right ovary with a small amount of ascites, suggesting a
      diagnosis of Meigs syndrome. The ovarian mass and the neighboring organs,
      including the uterus and the greater omentum, were surgically removed, and then
      both the bilateral pleural effusion and ascites disappeared after the surgery.
      The histopathological examination revealed that the mass was clear cell
      adenocarcinoma of the ovary (stage IIc), indicating that the disease was pseudo
      Meigs Syndrome. This is the second report of pseudo-Meigs Syndrome caused by
      clear cell adenocarcinoma of the ovary in Japan.

PMID- 15966372
TI  - [Two cases of pulmonary infection by Mycobacterium abscessus in which drug
      susceptibility testing results conflicted with clinical courses].
AB  - We encountered two cases of pulmonary infection by Mycobacterium abscessus (M.
      abscessus). [Case 1] A 66-year-old man who had been treated for non-tuberculous
      mycobacterium in the past was admitted because of productive cough. His chest X
      ray film showed cavitation and direct microscopy of sputum revealed positive acid
      fast bacilli (AFB). He was given rifampicin (RFP), ethambutol (EB), and
      clarythromycin (CAM), and then his symptoms and radiographic findings improved.
      [Case 2] A 74-year-old man with multiple myeloma as an underlying disease was
      admitted because of a cavitation found on chest radiography and a positive result
      for AFB in his sputum. Standard antituberculous drug therapy with isoniazid
      (INH), RFP, EB, and pyradinamide (PZA) was initiated and then the chest
      radiographic findings improved. As M. abscessus was isolated two weeks after the
      induction of therapy, the therapeutic regimen was changed to another combination
      therapy consisting of EB, clarithromycin (CAM) and ciprofloxacin (CPFX), and then
      his symptoms and radiographic findings were further improved. In both cases, the
      bacilli found in their sputum were identified as M. abscessus by DNA
      hybridization. They were completely resistant to all anti-tuberculosis agents and
      many antibiotics with a high value of MIC. However, their symptoms, radiographic
      abnormalities and the results of sputum examination improved following
      chemotherapy. The results obtained by MIC measurement were inconsistent with the
      clinical outcomes. The measurement of the MIC value of antibiotics do not
      necessarily predict its therapeutic effect.

PMID- 15966373
TI  - [Pulmonary tuberculosis with cerebellar lesion in a patient after anti-TNF-alpha
      (infliximab) treatment for rheumatoid arthritis].
AB  - We report a case of pulmonary tuberculosis in a 51-year-old Japanese woman, who
      received treatment with infliximab for active rheumatoid arthritis. She had cough
      and sputum after the second infusion of the drug, small nodular lesions of right
      lung field and left lower lobe on her chest CT and a small nodular lesion of
      right cerebellar lobe on her cranial MRI were identified. Mycobacterium
      tuberculosis was cultured from her sputum. Therefore, we diagnosed her illness as
      pulmonary tuberculosis with a cerebellar lesion. The patient was treated with
      anti-tuberculosis drugs and showed marked improvement in lesions of the lung and
      brain. We considered this case a tuberculosis reactivation after infliximab
      treatment because of the short interval between the administration of infliximab
      and the occurrence of tuberculosis, and the complication of extrapulmonary lesion
      that suggested brain tuberculoma.

PMID- 15966374
TI  - [A case of Kimura's disease accompanied with bilateral, mediastinal and hilar
      lymphadenopathy].
AB  - A 52-year-old man presented with general fatigue and body weight loss. Chest X
      ray and computed tomography showed bilateral, mediastinal and hilar
      lymphadenopathy. Laboratory tests revealed that peripheral eosinophils
      (1,850/microL) and serum IgE levels (1,610 U/L) were markedly increased. Cervical
      lymph node biopsy was performed for a definitive diagnosis. Histopathological
      analysis, using conventional H&E staining, showed mild infiltration of
      eosinophils into lymphoid follicules in the cervical lymph node.
      Immunohistopathological analysis, using an anti-human IgE antibody, showed mesh
      like IgE positive staining in lymphoid follicles. These clinical and pathological
      findings are compatible with a diagnosis of Kimura's disease.

PMID- 15966375
TI  - [A case of adenocarcinoma of lung with idiopathic pulmonary fibrosis, showing 1 8
      fluorodeoxyglucose uptake in positron emission tomograhy].
AB  - A 61-year-old man consulted our hospital because of bloody sputum. Cells of Class
      V (adenocarcinoma) were found on sputum cytologic examination. Chest computed
      tomography (CT) showed reticular shadows but no obvious mass was detected.
      Positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) revealed FDG
      uptake in both lower lung fields and more increased FDG uptake in a small area of
      the left lung field. Repeated chest CT, bronchial brushing, bronchial washing,
      and lung-imaging fluorescence endoscopy were performed, however, resulting in no
      detection of the primary site of lung cancer. Six months after initial
      consultation, chest CT showed an enlargement of the shadow in left S6
      corresponding to the area of the more increased FDG uptake in PET. On the other
      hand, the shadow in right S10 did not change in size. Bronchial brushing of the
      left S6 was performed again, and class IV cells (adenocarcinoma) were found.
      After left lower lobectomy, diagnoses of well differentiated adenocarcinoma and
      usual interstitial pneumonia (UIP) were established histologically. There has
      been no report demonstrating the efficacy of FDG-PET for diagnosis of lung cancer
      with idiopathic pulmonary fibrosis (IPF).However, combination of lung cancer
      should be considered if PET shows spots of high FDG uptake in the lung fields of
      IPF.

PMID- 15966376
TI  - [Effects of landiolol on cardiovascular responses, bispectral index and body
      movement during endotracheal intubation].
AB  - BACKGROUND: We investigated the effects of a novel highly cardioselective short
      acting beta-blocker, landiolol, on cardiovascular response, bispectral index and
      body movement during endotracheal METHODS: Forty ASA class 1 patients were
      randomly allocated into 2 groups, in a double-blind fashion; 1) 20 patients
      received landiolol 125 microg x kg(-1) x min(-1) for one minute followed by 40
      microg x kg(-1) x min(-1) (landiolol group), and 2) 20 patients received saline
      (control group). Landiolol or saline was started 6 min after a target controlled
      infusion of propofol (effect-site concentration 4 microg x ml(-1)). The trachea
      was intubated 11 min after propofol infusion. Heart rate, mean arterial pressure,
      and bispectral index were recorded. In addition, the "isolated forearm" technique
      was used to detect body movement during endotracheal intubation. RESULTS: Maximum
      changes in heart rate (control; 48% versus landiolol; 19%), mean arterial
      pressure (51% versus 39%), and bispectral index (31% versus 12%) observed during
      endotracheal intubation were significantly less in the landiolol group. More
      patients in the control than in the landiolol group moved after endotracheal
      intubation (19 versus 11, P<0.05). CONCLUSIONS: Our results suggest that
      landiolol infusion was effective to attenuate the hemodynamic, arousal and
      somatic responses to endotracheal intubation.

PMID- 15966377
TI  - [A randomized double-blind comparison of epidural versus intravenous tramadol
      infusion for postoperative analgesia].
AB  - BACKGROUND: This study compared epidural and intravenous tramadol infusions for
      postoperative analgesia after gastrectomy. METHODS: Twenty patients were assigned
      randomly to receive either tramadol epidurally and saline intravenously (group-E)
      or tramadol intravenously and saline, epidurally (group-I) in a double-blind
      fashion. At the end of the operation, each patient received a bolus of tramadol 2
      mg x kg(-1) either epidurally or intravenously and 7 mg x kg(-1) x day(-1)
      tramadol infusion was begun via the same route. Concurrently, a saline bolus and
      its infusion were given via the alternate route. RESULTS: Both groups obtained
      adequate pain relief and there was no difference between the groups in pain
      score. But one patient in E-group was excluded from the study for respiratory
      depression 8 hours after the operation. No other side effects were detected in
      either group except mild nausea. CONCLUSIONS: We conclude that intravenous
      tramadol infusion provides effective and safe postoperative analgesia. A futher
      examination is required for the suitable dose of tramadol in epidural infusion.

PMID- 15966378
TI  - [Perioperative complications of patients with cementless femoral head
      replacement].
AB  - BACKGROUND: Studies have shown that use of cement is a risk factor for fat
      embolism in elderly patients with femoral neck fracture. We investigated the
      usefulness of the cementless femoral head replacement technique. METHODS: A
      retrospective study of 58 patients who had undergone this technique between
      January 1995 and May 2001 was conducted. Perioperative complications, hospital
      length of stay, activities of daily living, and postoperative mortality were
      studied. RESULTS: Of 58 patients, 42 (72.4%) were fe- males, and the mean age was
      75.4 years. Twenty patients (69.0%) were classified as ASA class 2, and 50
      patients (86.2%) had preoperative medical complications. Cardiovascular
      complications were the most prevalent, and 6 patients (10.3%) had serious
      perioperative complications, and postoperative death was noted in 1 patient
      within one month (1.7%), and 4 patients (6.9%) within one year. Average length of
      hospital stay was 64.2 days and activities of daily living were the same level as
      before the fracture. CONCLUSIONS: Early rehabilitation was possible and hospital
      length of stay and activities of daily living were not inferior to the other
      treatments. We believe that cementless femoral head replacement technique was
      useful for elderly patients.

PMID- 15966379
TI  - [Efficacy of continuous subcutaneous pentazocine infusion for the postoperative
      analgesia in lower abdominal surgery].
AB  - BACKGROUND: Continuous subcutaneous infusion (CSI) of analgesics may be an
      alternative for pain control in patients without an epidural catheter. The aim of
      this study was to investigate the efficacy of CSI using pentazocine in lower
      abdominal surgery with inhalation anesthesia or with total intravenous
      anesthesia. METHODS: One hundred forty-seven patients scheduled for gynecological
      abdominal surgery were analyzed retrospectively. Anesthesia was induced with
      propofol and was maintained with propofol infusion or isoflurane-nitrous oxide
      inhalation. All patients received 30-75 mg of pentazocine before incision. At the
      end of surgery, CSI of pentazocine was begun at a rate of 0.5 ml x hr(-1) x Given
      regimen was pentazocine 240-390 mg and droperidol 5 mg with 1% lidocaine, and the
      total amount of dose was 40 ml. RESULTS: Over 80% of patients were assessed to
      have effective pain relief and minimum side effects. Patients were classified
      into two groups by anesthetics during anesthesia; propofol, pentazocine, ketamine
      group (PPK group, n = 61); nitrous oxide, isoflurane, pentazocine group (GOI
      group, n=88). There were no differences between the two groups regarding
      postoperative pain relief, while total dose of pentazocine used during anesthesia
      were lower in GOI group than PPK group. CONCLUSIONS: In patients undergoing lower
      abdominal surgery, CSI of pentazocine provided effective postoperative pain
      relief and effectiveness did not depend on anesthetics during anesthesia.

PMID- 15966380
TI  - [A comparison of propranolol with esmolol for the treatment of tachycardia during
      emergence from anesthesia].
AB  - BACKGROUND: Treating tachycardia occurring during emergence from general
      anesthesia is of the highest priority, because it frequently induces myocardial
      ischemia. Therefore we retrospectively compared the efficacy of esmolol with that
      of propranolol against such tachycardia. METHODS: Propranolol (n=22) or esmolol
      (n= 29) was given intravenously when the heart rate was above 100 beats x min(-1)
      during emergence from anesthesia. The drugs were titrated to decrease the heart
      rate the level before the induction of anesthesia. RESULTS: The total dose of
      propranolol was 0.52+/-0.21 mg (mean+/-SD), which decreased the heart rate
      significantly from 109.2 +/- 19.0 to 89.2 +/-11.8 beats x min(-1). The total dose
      of esmolol was 32.8 +/- 16.2 mg, which decreased the heart rate significantly
      from 110.0+/-13.9 to 84.9+/-10.7 beats x min(-1). The time required for the
      maximum effect of esmolol (3.2 1.8 min) was significantly shorter than that of
      propranolol (8.2 +/- 4.9 min). There were no episodes of adverse effects in
      either group. CONCLUSIONS: Both propranolol and esmolol are equally effective and
      safe for the treatment of tachycardia during emergence from anesthesia. The time
      required for the maximum effect of esmolol was shorter than that of propranolol,
      indicating an advantage of esmolol.

PMID- 15966381
TI  - [Which anesthetic technique is more suitable for hip fracture surgery in patients
      above the age of 85, spinal or epidural?].
AB  - BACKGROUND: Anesthesia for hip fracture in elderly patients is a challenge
      because of their reduced functional reserve. We compared spinal and epidural
      anesthesia retrospectively in the operations of hip fracture in patients above
      the age of 85. METHODS: Two hundred and eighteen operations from April 1995 to
      September 2003 in our hospital were examined. Epidural anesthesia was scheduled
      in 94 operations, and bupivacaine spinal anesthesia in 86 operations. Successful
      anesthetic cases of each group were compared. Blood pressure, heart rate, doses
      of vasopressors used were recorded before anesthesia and first and second 30
      minute periods after anesthesia. RESULTS: Failed anesthetic cases in epidural
      anesthesia were significantly more than those in spinal anesthesia. Blood
      pressure in the first 30-minute period after epidural anesthesia was
      significantly lower than that after spinal anesthesia. CONCLUSIONS: Spinal
      anesthesia is preferable for the operation for hip fracture compared with
      epidural anesthesia, because of fewer failed cases and smaller decreases of blood
      pressure.

PMID- 15966382
TI  - [Does common cold increase perioperative respiratory complications in adults?].
AB  - BACKGROUND: We investigated whether perioperative respiratory complications
      increase in adults with common cold symptom. METHODS: Thirty patients who had had
      a common cold (nasal congestion, rhinorrhea, sneeze, cough, sputa, or fever) in
      two weeks before general anesthesia and other 30 patients without any symptoms
      were enrolled in this study. All the patients were anesthetized with intravenous
      or inhalation anesthetics and were intubated. The incidences of bronchospasm,
      laryngospasm, dry or moist rale on lung field, increase in sputa or cough, and
      fever were checked during and for 5 days after, surgery. RESULTS: More patients
      with common cold showed dry or moist rale, increase in sputa or cough, and fever
      than those without common cold. Even though these were not statistically
      significant, three severe complications, respiratory as well as cardiac arrest,
      pneumonia, and prolonged intubation due to increased sputa, were observed.
      CONCLUSIONS: General anesthesia with oro-tracheal intubation should be postponed
      at least two weeks after common cold in adults.

PMID- 15966383
TI  - [Combined paravertebral lumbar plexus and parasacral sciatic nerve block for
      reduction of hip fracture in four patients with severe heart failure].
AB  - We experienced four cases of anesthesia for hip fracture reduction in patients
      with severe heart failure, where anesthesia was attempted with combined
      paravertebral lumbar plexus and parasacral sciatic nerve block instead of spinal
      anesthesia. The anesthesia was successful without any sequelae. The patients'
      characteristics are as follows. Case 1: 97-year-old woman with severe heart
      failure and old myocardial infarction. Case 2: 91-year-old man with pacemaker,
      heart failure and heart valve disease. Case 3: 93-year-old woman with severe
      heart failure and multi-vessel coronary artery stenosis. Case 4: 83-year-old
      woman with congestive heart failure and heart valve disease. Paravertebral lumbar
      plexus block was performed with Touhy needle which was directed to lumbar
      transverse process, then re-directed caudally. Psoas compartment was felt with
      loss of resistance. Twelve ml of 0.25% bupivacaine was injected. Sciatic nerve
      block was performed with a needle which was inserted at the midpoint between the
      greater trochanter and the sacral hiatus without (case 1, 2) or with nerve
      stimulator (case 3, 4). Eight ml of 0.25% bupivacaine was injected. During the
      anesthesia, propofol was injected for light sedation. Although this combined
      nerve block is difficult to perform compared with spinal anesthesia, this could
      be applicable for hip fracture reduction anesthesia, especially in patients with
      severe heart failure.

PMID- 15966384
TI  - [Early postoperative complications in patients with Moyamoya disease--a
      comparison of inhaled anesthesia with total intravenous anesthesia (TIVA)].
AB  - BACKGROUND: Moyamoya disease is a rare neurovascular disorder that requires
      special anesthetic managements during revascularization procedures. We have
      investigated the incidence of early postoperative complications under inhaled
      anesthesia in comparison with total intravenous anesthesia (TIVA)
      retrospectively. METHODS: Seventy-two patients undergoing revascularization
      procedures were divided into two groups, one with inhaled anesthesia (n = 23) and
      the other with TIVA (n = 49). Surgical procedures were performed under
      normocapnia, proper body temperature, and all patients were prevented from anemia
      by homologous transfusion. To avoid the variance in anesthetic managements, 39
      patients under 15 years of age were picked up and divided in the same way as
      above. Early postoperative complications including transient ischemic attack and
      cerebral infarction during the first 2 weeks after operation were investigated.
      RESULTS: In all patients, early postoperative complications occurred in 48% of
      inhaled anesthesia group and in 49% of TIVA group. In patients under 15, these
      complications occurred in 44% and in 57%, respectively. There was no significant
      difference in the incidence of complications between the two anesthetic groups.
      CONCLUSIONS: Several previous studies reported the excellence of TIVA for
      revascularization procedure on the basis of regional blood flow because inhaled
      anesthesia may provoke intracerebral steal in moyamoya disease. Our investigation
      in this study revealed that both anesthetic methods have no significant
      difference in postoperative complications during the first 2 weeks after
      operation. Thus further study should be needed to verify the safety of inhalation
      anesthetics in patients with moyamoya disease.

PMID- 15966385
TI  - [Sudden difficulty in ventilation due to massive subcutaneous emphysema during
      laparoscopic cholecystectomy].
AB  - A 56-year-old woman with cholecystolithiasis was scheduled for laparoscopic
      cholecystectomy. Anesthesia was induced with fentanyl and propofol IV, and the
      trachea was intubated using vecuronium IV. Anesthesia was maintained with 60%
      nitrous oxide and propofol intravenously, and vecuronium was used for muscle
      relaxation. Following induction of carbon dioxide pneumoperitoneum, PETCO2
      slightly increased. During pneumoperitoneum PETCO2 as easily controlled by
      increasing minute volume of ventilation. Fifty minutes after the start of
      pneumoperitoneum, suddenly the peak airway pressure increased and PETCO2 reached
      70 mmHg continuously. At this time, severe massive subcutaneous emphysema from
      the anterior thorax to the head and neck was noted, and the manual lung
      ventilation was very difficult. After discontinuation of pneumoperitoneum, PETCO2
      gradually decreased with improvement of the neck subcutaneous emphysema. At the
      same time the lung ventilation improved. We speculate that major causes of
      difficulty in ventilation were the decreased compliance and the tracheal tube
      comppression, which were due to massive subcutaneous emphysema. Our findings show
      that we have to stop pneumoperitoneum immediately, when we find a sudden increase
      of the peak airway pressure or PETCO2 with subcutaneous emphysema during
      laparoscopic cholecystectomy.

PMID- 15966386
TI  - [Persistent apnea in an obese patient with myotonic dystrophy].
AB  - We report a case of a 35-year-old woman with myotonic dystrophy and severe
      obesity of BMI 43.3 who showed persistent apnea at emergence after ovarian
      resection. The patient received an iv induction with minimum dose of propofol and
      vecuronium 3 mg. Anesthesia was maintained with propofol, 50% nitrous oxide and
      50% oxygen mixture and epidural anesthesia. Additional vecuronium 0.5 mg was
      administered twice. Surgery was performed uneventfully within 130 minutes and iv
      propofol was discontinued. The patient awoke promptly after termination of
      nitrous oxide but no spontaneous breathing appeared with end-tidal CO2 of 60
      mmHg. Because she could obey the order to breathe, the endotracheal tube was
      removed 40 minutes after discontinuation of propofol. Spontaneous breathing at
      the rate of 17 x min(-1) started soon after extubation. We assume that this apnea
      was caused by breath holding. Whether this breath holding is specific to myotonic
      dystrophy or not, anesthesia for patients with this disease requires careful
      attention for perioperative respiratory management.

PMID- 15966387
TI  - [Transient right bundle branch block during anesthesia].
AB  - Transient right bundle branch block occasionally occurs under anesthesia. We
      report a case of heart rate dependent right bundle branch block during
      sevoflurane anesthesia. A 74-year-old man was scheduled for partial hepatectomy.
      Past medical history was unremarkable, and preoperative electrocardiogram showed
      no conduction abnormalities. Operation was performed with epidural and general
      anesthesia. Five hours after induction of general anesthesia, complete right
      bundle branch block (CRBBB) occurred gradually without any hemodynamic changes.
      Although CRBBB persisted in his electrocardiogram (ECG) during surgery, recovery
      to normal conduction was observed 8 hours after surgery. The 12-lead ECG after
      disappearance of CRBBB was normal. There was no change in his vital signs and
      subjective symptoms. Serum level of creatine phosphokinase (CPK) isoenzyme was
      within normal ranges, and change of ventricular conduction corresponded with the
      change of heart rate. These observations suggest that transient CRBBB in this
      case was rate dependent.

PMID- 15966388
TI  - [Severe hypotension after induction of general anesthesia in a patient receiving
      an angiotensin II receptor antagonist and an alpha-blocker].
AB  - We report severe hypotension after induction of general anesthesia in a patient
      receiving an angiotensin II receptor antagonist and an alpha-blocker. A 50-year
      old man with diabetes mellitus who had been treated with candesartan cilexetil
      and doxazosin was scheduled for vitreous surgery. He was operated on for vitreous
      surgery three times. He developed severe hypotension after induction of
      anesthesia with propofol and fentanyl on two occasions, when he was taking
      candesartan cilexetil and doxazosin. Repeated injections of intravenous ephedrine
      could not raise the blood pressure. After discontinuation of both drugs, although
      he developed hypotension after induction of anesthesia with propofol and
      fentanyl, hypotension was mild and responded promptly to intravenous ephedrine.

PMID- 15966389
TI  - [Anesthetic management for nephrectomy in a 2-year-old girl with abdominal aortic
      aneurysm].
AB  - We report anesthetic management for nephrectomy in an infant with aortic
      aneurysm. A 2-year-old girl with renovascular hypertension and abdominal aortic
      aneurysm, who had shown repeated episodes of heart failure, was scheduled for
      nephrectomy. Anesthesia was induced with sevoflurane in nitrous oxide (70%) and
      oxygen. During the surgery, anesthesia was maintained with sevoflurane (1.5%) in
      nitrous oxide (50%) and oxygen, supplemented with intermittent epidural block.
      The blood pressure did not show marked changes during the surgery. There was no
      perioperative cardiovascular complication.

PMID- 15966390
TI  - [Anesthetic management of a teenage athlete who developed arrhythmia during
      general anesthesia].
AB  - A 17-year-old man with fracture of the mandible underwent open fixation under
      general anesthesia. He was an athlete of the rugby suffering the fracture in a
      match. His preoperative physical examinations were normal except for I degrees
      atrioventricular block on electrocardiogram (ECG). During anesthesia,
      atrioventricular dissociation and frequent premature ventricular contractions
      were induced by the stimulation of nasotracheal intubation and the administration
      of atropine for the reversal of muscle relaxation. We thought the cause of the
      arrhythmia is the athlete's heart which may be vagotonic and may induce vagal
      reflex or fatal arrhythmia. This case demonstrates that it is necessary to pay
      attention to chronotropic action associated with the intubation of nasopharynx,
      the handling of laryngoscope and the usage of drugs for the anesthetic management
      of the athlete.

PMID- 15966392
TI  - [Bilateral recurrent laryngeal nerve paralysis in a child following a
      neurosurgical operation].
AB  - We experienced a case of 7-year-old boy who developed bilateral recurrent
      laryngeal nerve paralysis following an elective neurosurgical operation under
      oxygen-nitrous oxide-isoflurane anesthesia. He underwent a removal of brain tumor
      in the supratentorial region on supine position. After the removal of the
      endotracheal tube in the intensive care unit, he developed marked respiratory
      effort and inspiratory stridor. A diagnosis of bilateral recurrent laryngeal
      nerve paralysis was made by a direct diagnostic laryngoscopy. The patient needed
      continuous care for his airway patency with tracheotomy tube in place, and his
      normal vocal cord mobility recovered on the 23 rd postoperative day. Common cause
      of recurrent nerve injury following general anesthesia is either the procedure of
      endotracheal intubation itself or trauma due to surgical manipulation. In the
      present case, an endotracheal tube, a transesophageal stethoscope and a
      nasogastric tube inserted into the narrow laryngeal space might have been a cause
      of this complication. Moreover, accidental extreme flexion of his neck which
      occurred during the surgery might also be an additional cause. This case suggests
      that recurrent laryngeal nerve paralysis due to anesthetic instruments around the
      larynx is a possible cause of complications during general anesthesia in
      pediatric patients.

PMID- 15966391
TI  - [Perioperative management of a patient with subarachnoid hemorrhage complicated
      with descending aortic dissection].
AB  - A 62-year-old man with descending aortic dissection received general anesthesia
      for clipping of aneurysm of the cerebral artery. We chose a surgical operation
      for the aneurysm of the cerebral artery, and conservative therapy for the
      dissection of the aorta. We gave balanced anesthesia with blood pressure control
      using calcium channel blocker. Anesthesia was induced with propofol, fentanyl,
      and vecuronium, and maintained with isoflurane, fentanyl, nitrous oxide and
      oxygen. Transesophageal echocardiography was useful for checking dissection of
      the aorta. Perioperative course was uneventful.

PMID- 15966393
TI  - [General anesthesia outside the operating room in patients with Pierre-Robin
      syndrome].
AB  - Anesthesiologists are increasingly asked to involve in administering general
      anesthesia outside the operating room for such procedures as computed tomography,
      magnetic resonance imaging or angiography. Especially, pediatric patients require
      some kind of sedation or general anesthesia during these procedures. We report
      general anesthesia outside the operating room in patients with Pierre-Robin
      syndrome, who are expected to have possible difficult airway. A one-year-old girl
      and a 16-year-old boy were anesthetized for cardiac catheterization. General
      anesthesia was given at the angiography room which was located outside the
      operating room. Anesthesia was induced with oxygen, nitrous oxide and sevoflurane
      while portable storage unit for difficult airway was prepared including various
      types and size of laryngoscopes, laryngeal mask airway, fiberoptic intubation
      equipment and surgical airway access. Fortunately, tracheas were successfully
      intubated without using special devices, although cautious care during induction
      was taken. According to development of medical and surgical procedures, it is
      readily presumed that anesthesiologists will be more often involved in the
      sedation or anesthesia conducted outside the operating room in future.
      Anesthesiologists should always ensure enough staffing, proper monitoring and
      equipment when sedation or anesthesia is conducted outside the operating room,
      particularly if patients have anesthetic risks.

PMID- 15966394
TI  - [Cricoarytenoid arthritis diagnosed after tracheostomy in a rheumatoid arthritis
      patient].
AB  - A 65-year-old woman was scheduled for total knee replacement. She had been
      suffering from rheumatoid arthritis for 22 years. She also had a history of
      occasional acute dyspnea, which had been diagnosed as asthmatic bronchitis.
      Preoperative examinations of the airway revealed limited neck flexion, a small
      jaw, and normal mouth opening. After epidural catheterization, anesthesia was
      induced with propofol, and a #3 laryngeal mask airway (LMA) was inserted.
      However, her lungs could not be ventilated through the LMA. Despite repeated
      attempts, proper placement of the LMA could not be achieved. Hence, a 7.0 mm ID
      armored endotracheal tube was inserted through an intubating LMA. Anesthesia was
      maintained with nitrous oxide and sevoflurane in oxygen. The surgery proceeded
      uneventfully. Five minutes after extubation, inspiratory dyspnea occurred. The
      patient's trachea was re-intubated nasally with a bronchofiberscope. Since the
      bronchofiberscopy revealed remarkable laryngeal edema, percutaneous tracheostomy
      was performed. On the 3 rd postoperative day, cricoarytenoid arthritis that had
      caused occasional airway obstruction was diagnosed, although her laryngeal edema
      disappeared. She went home with a permanent tracheostomy. Although cricoarytenoid
      arthritis is a common occurrence in patients with rheumatoid arthritis, the
      diagnosis can be difficult. A scrupulous preoperative evaluation and awareness of
      cricoarytenoid arthritis are necessary for optimal anesthetic management.

PMID- 15966395
TI  - [Incidence of inappropriate cases for training of emergency medical technicians
      in endotracheal intubation].
AB  - BACKGROUND: Before emergency medical technicians are licensed to perform
      prehospital endotracheal intubation, they must undergo training in the operating
      room setting. We investigated the incidence of cases of difficult intubation
      classified as Cormack & Lehane grade III or IV, because such cases are considered
      inappropriate for training emergency medical technicians. METHODS: We examined
      anesthesia records between March 2002 and April 2003, retrospectively. The survey
      included 585 adult surgical patients with ASA physical status I or II requiring
      general endotracheal anesthesia. RESULTS: Five anesthesiologists and three
      doctors from the surgical department performed laryngoscopy during this period.
      In initial laryngoscopy with a Macintosh blade, the view of larynx was grade I in
      436, grade II in 98, grade III in 27 and grade IV in 24 patients. In 68 patients,
      application of cricoid pressure led to improvement of laryngoscopy grade. The use
      of McCoy blade was necessary for intubation in 16 patients. Out of 51 patients
      classified as difficult intubation grade III or IV, 35 were originally not
      expected to be difficult cases. CONCLUSIONS: Patients with grade I or II view of
      larynx with a Macintosh blade was only 91%. In order to prepare for unexpected
      case of difficult intubation, it is necessary to take various measures such as
      having instructors perform laryngoscopy.

PMID- 15966396
TI  - [Gender related problems in medicine--an analysis of questionnaire to male
      anesthesiologists].
AB  - BACKGROUND: There is little information on gender related problems in medicine
      from a point of view of the male anesthesiologists. METHODS: A questionnaire was
      sent in January 2001 to 300 male anesthesiologists. The questionnaire asked for
      information on personal and professional demographics, gender inequity, and
      family responsibility. RESULTS: Of the 186 responding male anesthesiologists
      (62.0% response rate), 62.4% of them felt a gender inequity. They felt a gender
      inequity the most in family responsibility (40% of them). In contrast, those who
      felt a gender inequity in working ability and promotion were small in number
      (4.1%, 14.1%, respectively). More than 80% of male anesthesiologists agreed on
      the need of consideration about night-duty for the female anesthesiologists. On
      the other hand, 66.7% of them felt that taking place of the female
      anesthesiologists was a burden on them. CONCLUSIONS: More than half of male
      anesthesiologists felt a gender inequity especially in family responsibility. In
      addition, it is impressive that most of male anesthesiologists were unaware of
      gender inequity in promotion in face of the fact that the number of the female
      professors was very small. Systemic effort is required to grapple with gender
      inequity problems to change the social organization in the field of medicine.

PMID- 15966397
TI  - [Clinical evaluation of ECG at the onset subjective symptoms using real-time
      analysis electrocardiograph (event recorder)].
AB  - Examination of patient complaining of palpitation, chest pain and chest
      discomfort is usually performed by 12-lead electrocardiograph. However, the
      recording time is short and there are few opportunities to capture an ECG
      demonstrating conditions during subjective symptoms. To investigate the cause, we
      need to obtain an ECG during subjective symptoms. Thus, we frequently use a
      Holter ECG, which can be recorded for 24 hours. However, some patients have a low
      frequency of subjective symptoms, which may not appear during a 24-hour
      examination. We used a real-time electrocardiograph (Event Recorder CG-6106 made
      by Card Guard Scientific Survival Limited) as a monitor during subjective
      symptoms. Thereafter, ECG findings at the onset of subjective symptoms could be
      analyzed in 30 patients who did not have a clear cardiac disease. In this
      examination, arrhythmia was recorded in 25 of 30 cases. Although in these cases
      ECG during subjective symptoms could not be captured even when Holter examination
      was performed several times ECG during subjective symptoms was captured using an
      Event Recorder. This method using an Event Recorder is simple and convenient,
      moreover, is considered very useful for investigation of subjective symptoms. In
      the future, the use of an Event Recorder for heart-health-care in the daily life
      of healthy people and/or cardiac disease patient is highly anticipated.

PMID- 15966398
TI  - [Development of a new method for diagnosing the origin of urinary bleeding by
      doghnut-shape urinary red blood cells].
AB  - Although the presence of acanthocytes (AC) is a reliable indicator of glomerular
      bleeding, acanthocytes could be observed in only 60% of patients with
      glomerulonephritis. Therefore, we attempted to develop a new method for
      diagnosing the origin of urinary bleeding by the morphological characteristics of
      doughnut-shaped of urinary red blood cells (RBC). In the present study, urine
      samples from 7 patients with glomerular bleeding and 4 patients with non
      glomerular bleeding, and from 35 urine samples of the glomerular bleeding and non
      glomerular bleeding-model were examined. The various type of RBC were observed by
      a phase contrast microscopic examination. The doughnut-shaped RBC were divided
      into three shapes (namely, smooth, uneven, target-shaped RBC) by individual
      characteristics. The appearance rate of each shape was calculated, and both outer
      and inner diameters of doughnut-shaped RBC in the photographs were also measured.
      Although there was no change in the value of outer diameter of doughnut-shaped
      RBC between glomerular bleeding and non-glomerular bleeding, the values of inner
      diameter of doughnut-shaped RBC in non-glomerular bleeding was significantly
      smaller than those in glomerular bleeding in all shapes. These results strongly
      suggested that the measurement of inner diameters of doughnut-shaped RBC is one
      of the useful diagnostic methods to distinguish the origin of urinary bleeding
      when AC could not be observed.

PMID- 15966399
TI  - [The assessment of arteriolosclerosis by serum lipids data, and carotid
      ultrasonography and pulse wave velocity, and its evaluation as a tool for
      preventive medicine: II. Carotid ultrasonography and pulse wave velocity for
      hyperlipemia and diabetes mellitus].
AB  - We studied the test results of carotid ultrasonography and pulse wave velocity
      against a sample of hyperlipemia and diabetes mellitus. Sixty four hyperlipemia
      samples (HL), 85 diabetes mellitus samples (DS), and 27 complicated samples (CS)
      were compared with 56 healthy samples (HS). Hyperlipemia samples were selected
      from cholesterol under 300 mg/dl, and neutral fat under 300 mg/dl. Diabetes
      mellitus samples were selected from fasting plasma glucose (FBS) under 200 mg/dl.
      Samples from severe conditions with various disease were excluded. Ratio over 1.1
      mm intima-media thickness (IMT) was 0% in HS, 48% in HL, 40% in DS and 33% in CS.
      PWV value was max 1896cm/s in CS. There was no significant correlation within
      IMT, serum lipid(Total Cholesterol, Neutral Fat, HDL-Cholesterol, LDL
      Cholesterol) and FBS. For early treatment or accurate diagnosis of
      arteriosclerosis in hyperlipemia or diabetes mellitus patients, who are at high
      risk of developing arteriosclerosis, to vital function tests (carotid
      ultrasonography and pulse wave velocity) should be performed, in addition to
      normal blood tests.

PMID- 15966400
TI  - [Incidence and characteristics of intestinal hyperphosphatasemia in healthy
      subjects].
AB  - We recently reported that two intestinal alkaline phosphatase (IAP) isoforms,
      high molecular mass IAP (HIAP) and normal molecular mass IAP (NIAP), appear in
      healthy serum with our Triton-PAGE method for determination of ALP isozymes. In
      addition, HIAP is chiefly present in blood group B or O secretors, and a large
      amount of NIAP is secreted into the circulation in blood group B or O secretors.
      In the present paper, we examined incidences and characteristics of intestinal
      hyperphosphatasemia in healthy subjects and blood groups dependent
      hyperphosphatasemia. We classified 273 healthy women into two groups of blood
      group B or O secretors (n = 105) and other blood groups (n = 168). Intestinal
      hyperphosphatasemia in healthy subjects only appeared in sera of B or O blood
      group secretors, and incidence of intestinal hyperphosphatasemia was 26.6%
      (28/105). In addition, blood groups dependent hyperphosphatasemia, more than 350
      U/l of ALP activity, was 21.4% (6/28) of intestinal hyperphosphatasemia in
      healthy subjects, and 5.7% (6/105) of blood group B or O secretors. These results
      suggested that blood groups dependent hyperphosphatasemia in healthy subjects was
      closely related to the HIAP and NIAP levels.

PMID- 15966401
TI  - [Analysis of salivary testosterone by liquid chromatography-tandem mass
      spectrometry: correlation with serum bioavailable testosterone and aging].
AB  - PURPOSE: To demonstrate that the salivary testosterone (T) concentration measured
      by liquid chromatography tandem mass spectrometry (LC-MS/MS) is a sensitive
      biomarker of serum bioavailable testosterone (bio T) concentration and it's
      decrease with age. METHOD: Saliva and blood samples were collected from healthy
      53 Japanese men (16-66yr) three times a day (9: 00-10: 00, 13: 00-14: 00, 17: 00
      18: 00). Salivary T and serum total T levels were compared with serum bio T
      levels fractionated with concanavaline A. All samples were measured by LC-MS/MS.
      The stability of salivary T concentrations stored at -70 degrees C for 2 months
      was also examined. RESULTS: Salivary T levels correlated with bio T(r=0.88,
      n=158) better than total T did (r=0.71, n=159). The decrease of T concentration
      with age was observed in saliva of each sampling time. In total T, the decrease
      with age was weaker and was insignificant in the late afternoon. Salivary T was
      stable for 2 months at -70 degrees C and a freeze/thaw cycle (difference: average
      3.7%, SD=8.4%, n=84). CONCLUSIONS: Salivary T measured by LC-MS/MS is a reliable
      biomarker of T availability and its decrease with aging.

PMID- 15966403
TI  - [Consulting work performed by the hospital laboratory: the usefulness of the
      laboratory information office in Tenri Hospital].
AB  - We introduced a consultation process to the clinical laboratory in our hospital.
      The laboratory information room has been installed for three years in the
      hospital, and all questions concerning the laboratory tests are received. A
      clinical laboratory physician and an experienced medical laboratory technician
      address any complex or technical questions. The clinical laboratory physician is
      necessary in the laboratory information room because of his or her knowledge of
      the clinical tests based on clinical experience, and his or her knowledge of the
      aspects of epidemiology and laboratory management. Clinical experience is
      especially necessary to communicate between doctors and nurses and medical
      laboratory technicians. Because managing the business of the laboratory
      information room by a clinical laboratory physician alone is unrealistic for a
      lot of hospitals, most laboratory information room must have several medical
      laboratory technicians and a few clinical laboratory physicians to cooperate with
      them and help their work.

PMID- 15966402
TI  - [Analysis of reference values of serum S100B concentrations of Japanese adults].
AB  - PURPOSE: S100B is a calcium-binding protein which exists in abundance in glial
      cells of the central nervous system (CNS). It is reported that the serum S100B
      level increase with various CNS diseases, such as stroke, head injury,
      schizophrenia, major depression and Alzheimer's disease. However, there are no
      reports on its reference values for the Japanese. The purpose of this study is to
      know the serum S100B concentrations of Japanese adults, free of any CNS diseases,
      according to sex, age and circadian rhythm. Moreover, the stability and
      reproducibility of its measurements of S100B in frozen serum over 7 months.
      METHODS: Volunteers were 26 male and 25 female of Japanese adults. Venous blood
      samples were collected at given times of a day and serum was obtained by
      centrifugation at 4 degrees C. An automated chemiluminescence analyzer "LIAISON"
      and exclusive reagent Sangtec 100 (DiaSorin, Italy), was used for measurement of
      serum S100B concentrations. RESULTS: The serum S100B concentrations in Japanese
      adults corresponded well, with the reported values in Asians. Differences by age
      and sex were not found. S100B did not how circadian variation. The serum S100B
      concentrations measured in two months and in nine months after venipuncture were
      almost the same. CONCLUSION: The measurement of S100B by "LIAISON" showed
      excellent reproducibility and reliability. Furthermore, stability of serum S100B
      stored at -80 degrees C was good.

PMID- 15966404
TI  - [An ideal of future medical technologist and a relation with clinical laboratory
      physician].
AB  - As most important things one of medical care system reform of Japan, improvement
      of the medical treatment related of job was taken in. When it is accompanied to
      "An ideal of future medical technologist and a relation with clinical laboratory
      physician" from the meaning, it is necessary to just meet it and in needs at
      first to be clinical, does the basis with EBM early and time. In addition, it
      promotes the purchase of economic reagent/articles of consumption than it
      considered a medical care reward mark while taking that effective medical
      treatment of patient standard is demanded into consideration and introduces a
      system of ISO15189 of clinical laboratory. It is necessary for the charm that can
      support education more and research to aim at a certain medical technologist.
      Therefore it is for medical technologists to contribute to medical treatment
      while taking cooperation to be a clinical laboratory physician.

PMID- 15966405
TI  - [Molecular targeting therapy for leukemia by sphingolipid ceramide].
AB  - Ceramide has been recognized as a structural component to consist of the cell
      membrane. Since we reported that ceramide content increased in vitamin-D3-induced
      cell differentiation of human leukemia HL-60 cells, it has become evident that
      ceramide acts as an intracellular lipid mediator to transduce an extracellular
      stress into the cells. Ceramide is synthesized through serine-palmitoyl CoA
      transferase. Diversity of ceramide species derives from the changes of carbon
      length of fatty acid binding to amine part of sphingosine. A variety of stresses
      induce apoptosis through activation of pro-apoptotic signals as well as
      inhibition of antiapoptotic/survival signals by an increase of intracellular
      ceramide. Here, the recent problems and innovation in the medication of
      hematological malignancy are summarized, and it is suggested that the induction
      of apoptotic cell death by ceramide action is a potent, novel molecular targeting
      therapy for a chemoresistant and refractory hematological malignancy.

PMID- 15966406
TI  - [Risk factors for cerebrovascular diseases].
AB  - Cardiovascular diseases have been increasing in association with life style
      changes and increasing trends of hyperlipidemia and diabetes in Japan. On the
      other hand, cerebrovascular diseases, which largely comprise of small-vessel
      diseases such as hypertensive brain hemorrhage and lacunar brain infarction, have
      been considered to be dependent on aging and hypertension. Recently, however,
      atherothrombotic brain infarction (ATBI) has been rapidly increasing in Japan,
      and this increase occurs precedently in urban area such as Kanto and Kansai
      Districts. The present paper, therefore, summarizes the classification of diverse
      subtypes of cerebrovascular diseases and their underlying vascular lesions.
      Furthermore, it also focuses the risk factors for cerebrovascular diseases and
      the vascular lesions, and aims to clarify the factors and background which may
      have contributed to the increase of ATBI in Japan. Arteriosclerotic changes of
      small arteries in the brain parenchyma are considered to play an important role
      in development of cerebral white matter lesions (leucoaraiosis) and lacunar
      infarction. Oxidative stresses such as smoking, lipid peroxidation, and others
      are suggested to give impacts on the lesion formation through the effects on
      various functions of arterial trees and nitric oxide (NO) production from the
      arterial endothelial cells. Therefore, This paper presents the data indicating
      the significant correlation of these oxidative stress markers and polymorphism of
      endothelial NO synthase gene which may be relating to the pathogenesis of
      cerebral white matter lesions, and discusses about the usefulness of these new
      risk factors for cerebrovascular diseases.

PMID- 15966407
TI  - [Ischemic heart disease].
AB  - Ischemic heart disease is one of the leading causes of death in Japan. Acute
      coronary syndrome (ACS) most commonly begins with atherosclerotic plaque rupture
      and intracoronary thrombus formation. Therefore, the primary goal of treatment of
      acute coronary occlusion is the achievement of early and complete reperfusion. To
      achieve this goal, detection of atherosclerosis and/or myocardial necrosis by
      imaging and serologic tests is important. Original diagnosis of acute myocardial
      infarction (AMI) was made from typical symptoms, characteristic rises in serum
      enzyme levels, and an atypical electrocardiographic pattern. Increasingly
      sensitive and specific tests have been developed in recent years and have been
      rapidly adopted into clinical practice. Rapid developments in technology in the
      field of serum biomarkers have redefined the diagnosis of AMI. The new ESC/ACC
      criteria place increased emphasis on cardiac biomarkers, especially troponins.
      However, the electrocardiogram still remains significant in the diagnosis of AMI
      and the ability to identify high risk subgroups by admission electrocardiogram is
      necessary to estimate the severity of AMI. Current practice guidelines recognize
      the importance of promptly restoring normal epicardial blood flow, but blood flow
      to the ischemic tissue may still be impeded after relief of the occlusion; a
      phenomenon known as no reflow. Myocardial scintigraphy is one of the methods for
      defining coronary microvascular injury in the acute phase of AMI. Prompt
      assessment of coronary perfusion and detection of coronary microvascular injury
      may aid in making decisions concerning the use of drugs to improve microvascular
      function and left ventricular function after primary coronary angioplasty.

PMID- 15966408
TI  - [Proteome analysis of autoantibodies in sera of patients with cancer].
AB  - Circulating autoantibodies are useful diagnostic markers of cancers and
      autoimmune diseases. Research over the past decade has resulted in some reports
      on the presence of autoantibodies against disease-related proteins such as
      annexin-I & II, recoverin and protein gene product 9.5 in the sera of patients
      with lung cancer, and also against calreticulin and alpha-enolase in autoimmune
      diseases. In this study, we first identified the a-enolase autoantibody in the
      sera of patients with lung adenocarcinoma by proteomics-based analysis. The
      comparison of two-dimensional polyacrylamide gel electrophoresis (2D
      PAGE)/western blot (WB)/ECL detection revealed distinct distributions of
      antibodies in the sera of lung adenocarcinoma, tuberculosis and healthy subjects
      which reacted with soluble proteins derived from the adenocarcinoma A549 cell
      line. We found 16 spots in patients with adenocarcinoma by 2D-PAGE/WB/ECL
      detection and identified alpha-enolase, chaperonin, and other autoantibodies in
      the adenocarcinoma patients' sera. The specificities of an antibody against alpha
      enolase was preliminarily observed in sera from 3 of 5 patients with
      adenocarcinoma, 0 of 10 patients with tuberculosis and 0 of 10 healthy subjects.
      In conclusion, we first identified alpha-enolase autoantibody in sera of lung
      adenocarcinoma and the autoantibody was seemed to be a specific marker of the
      lung adenocarcinoma. In addition, we also identified various autoantibodies in
      esophageal cancer, hepatocellular carcinoma, and non-Hodgkin's lymphoma.
      Moreover, we tried to identify the corresponding antigen of an unknown anti
      cytoplasmic autoantibody, and an anti-red blood cell antibody by proteomics-based
      analysis. These antibodies might become new diagnosis markers.

PMID- 15966409
TI  - [Diagnostic tests approved by Ministry of Health and Welfare].

PMID- 15966410
TI  - [Preparing with the eventuality of an influenza pandemic].

PMID- 15966411
TI  - [Choices in child care assistance].

PMID- 15966412
TI  - [Rickettsioses].
AB  - Rickettsioses can present with protean manifestations. Recent progress in
      molecular biology allows a better classification of the array of pathogens
      involved. Rickettsial tick-borne diseases are of emerging importance given
      nowadays increased in international travellers. Because of substantial morbidity
      and mortality associated with a delay in diagnosing and treating these
      infections, awareness of both their geographical distribution and their clinical
      presentations is important, and the empirical administration of appropriate
      antibiotic is often justified. Travellers to endemic areas should be encouraged
      to use personal protective measures.

PMID- 15966413
TI  - [Parkinson's disease: dealing with all dimensions of the disease].

PMID- 15966414
TI  - [Circumstances of Parkinson's disease diagnosis].
AB  - Parkinson's disease is one of the most frequent neurodegenerative diseases. The
      usual characteristic signs combine the classical triad, rest tremor, bradykinesia
      and rigidity. The diagnosis is usually easy after several years, especially when
      the levodopa responsiveness is established, and most of the differential
      diagnosis can then be ruled out. However, the diagnosis of Parkinson's disease is
      not confirmed at autopsy in 25% of cases. The errors are much more frequent at
      disease onset since the clinical presentation may be insidious and may comprise
      non-motor signs such as pain, vegetative, sensory or neuropsychological signs. In
      the future, early recognition of the disease will become more and more important
      with the development of neuroprotective therapeutic strategies.

PMID- 15966415
TI  - [Therapeutic strategies for Parkinson's disease].
AB  - The remarkable efficacy of L-dopa on the akinesia, tremor and rigidity of
      Parkinson's disease is incontestable. It is responsible for the functional
      improvement and the regained quality of life. Unfortunately, after this classical
      "honeymoon" appear the "motor complications of dopamine therapy" (MCD), motor
      fluctuations and dyskinesia. Even more frequent and severe when the patient is
      young, it compromises the patient's autonomy. Certainly, the manipulation of L
      dopa, the modification of its metabolism, and its association with an agonist
      permit amelioration but this is inconstant, imperfect and brief. The pulsatility
      of dopaminergic stimulation is the determinant physiopathological element in the
      genesis of MCD. New strategies of anti-Parkinsonian treatment find there within
      their justification. Some of them aim to treat the MCD: the high frequency
      electric stimulation of the sub-thalamic core is the most recent example. The
      criteria of selection for the electric stimulation should be respected in order
      to ensure its efficacy. These symptomatic treatments however, have no influence
      on the natural history of the disease and/or the affect on other dopaminergic
      systems. Perhaps hope should rather be placed in neuroprotection.

PMID- 15966416
TI  - [Management of psychiatric complications of Parkinson's disease].
AB  - Psychic disturbances are frequently present in patients with Parkinson's disease.
      They increase the disability and handicap, contribute to poor quality of life and
      often make the treatment of motor symptoms more difficult. Cognitive impairment
      may be restricted to subtle changes on neuropsychological testing, but the
      evolution towards a dementia appears more frequent than previously thought.
      Depression, anxiety and hallucinations are common but may be underestimated.
      During recent years, new psychiatric aspects have been described such as apathy
      and the so-called syndrome of dopamine dysregulation.

PMID- 15966417
TI  - [Parkinson's disease and associated disorders].
AB  - Besides the core motor features of Parkinson's disease, other disorders such as
      gastro-intestinal dysfunction, postural hypotension, urinary, genital, sleep
      problems and pain contribute to the alteration of patient's quality of life.
      Drooling, swallowing difficulties and constipation are the more frequent
      digestive problems. Aspirations may be life-threatening. Sexual dysfunction as
      well as iatrogenic hypersexuality may be deleterious for the couple well-being.
      Symptomatic postural hypotension is the main manifestation of autonomic failure
      and needs a specific management. Pain is frequent in Parkinson's disease,
      particularly due to frozen shoulder or to the peculiar picture of "primary
      sensory pain symptoms". Sleep disorders are common in Parkinson's disease and are
      associated with reduced quality of life and increased risk of vehicle accident
      particularly when excessive daytime somnolence occurs.

PMID- 15966418
TI  - [Walking movements in Parkinson's disease].

PMID- 15966419
TI  - [Data on quality of health care: patients and physicians].

PMID- 15966420
TI  - [Facial paralysis].

PMID- 15966421
TI  - [Interpretation of epidemiologic studies].

PMID- 15966422
TI  - [Infective endocarditis].

PMID- 15966423
TI  - [Algodystrophy].

PMID- 15966424
TI  - [Population-based health indicators].

PMID- 15966425
TI  - [Delirium, depression, dementia in the elderly].

PMID- 15966426
TI  - [Documentary research and self-instruction. Critical reading of a medical
      article. Practice guidelines. Part 2: documentary research and self-instruction].

PMID- 15966427
TI  - [The Flaubert history of medicine museum in Rouen].

PMID- 15966428
TI  - [From the maniac-depressive disorder to the bipolar disorder].

PMID- 15966429
TI  - [The clinical admission of bipolar patients: reality].

PMID- 15966430
TI  - [Bipolar symptoms, frontal lobe symptoms].

PMID- 15966431
TI  - [Neuropsychology of bipolar disorder].

PMID- 15966432
TI  - [Neurobiological aspects of bipolar disorder].

PMID- 15966433
TI  - [Will genetics allow for the differentiation of schizophrenia and maniac
      depressive psychosis?].

PMID- 15966434
TI  - [Mixed states].

PMID- 15966435
TI  - [The concept of the schizo-affective disorder].

PMID- 15966436
TI  - [Bipolar disorder and medico-legal aspects].

PMID- 15966437
TI  - [Predictive criteria for a maniac admission].

PMID- 15966438
TI  - [The methodology of the studies in the treatment of maniac admissions].

PMID- 15966439
TI  - [100 years Medizinische Klinik Journal].

PMID- 15966440
TI  - [Quality assurance in medicine].

PMID- 15966441
TI  - [The Jo-1 Syndrome--immunological findings and clinical manifestations].
AB  - El The Jo-1 syndrome is an autoimmune disease which is characterized by the
      presence of autoantibodies against the Jo-1 antigen. The designation Jo-1 is
      derived from the name of the first patient (John P.) who was tested positive for
      this antibody. This patient suffered from polymyositis and fibrosing alveolitis.
      The Jo-1 antigen was identified as histidyl-transfer-RNA synthetase present in
      the cytosol. The Jo-1 syndrome is a member of a family of autoimmune diseases,
      called anti-synthetase syndromes. These syndromes are characterized by
      autoantibodies directed against aminoacyl-transfer-RNA synthetases. The etiology
      of the Jo-1 syndrome is unknown. The most frequent clinical manifestation is
      myositis, which may present as polymyositis or dermatomyositis. In addition to
      muscle involvement, interstitial lung disease is frequently found and critical
      for the prognosis. Furthermore, symptoms of other autoimmune disorders such as
      polyarthritis may occur. Similar to polymyositis and dermatomyositis, the Jo-1
      syndrome may present as myositis overlap syndrome. In these cases, antibodies
      against U1-RNP are detected. The Jo-1 syndrome responds to treatment with
      corticosteroids and, if necessary, azathioprine, methotrexate or
      cyclophosphamide. The clinical manifestations of the Jo-1 syndrome are
      illustrated by two clinical cases.

PMID- 15966442
TI  - [The critical incident reporting system (CIRS) as a measure to improve quality in
      medicine].
AB  - It may be seen as regrettable that a measure which is suitable for improvement of
      quality in medicine is broadly discussed only in the context of risk avoidance.
      The system of reporting adverse events (incidents), known under its
      internationally used term CIRS, is based on the observation that there is a close
      correlation between the occurrence of severe incidents with consequences and
      milder incidents or near misses without consequences. By avoiding mild incidents
      the severe incidents will automatical also be reduced. In contrast to a classic
      analysis of mistakes and errors the consequence itself only plays a minor role
      with CIRS. In Germany mistakes are usually seen under the aspects of a personal
      responsibility and they are prone to sanctions. But only when mistakes are
      accepted as occurring everywhere and with everybody and when they are regarded
      under the aspect of how to be avoided in future the necessary transparency can
      grow and an open dealing with mistakes can arise. This enables analyses with the
      only goal of quality improvement by avoidance of mistakes.

PMID- 15966443
TI  - [Quality Management in Hospitals. Relevance of KTQ].
AB  - With the KTQ (Cooperation forTransparency and Quality in Health Care) quality
      report patients and the referring physician obtain a general view of the standard
      of quality of the hospital. The KTQ certificate demonstrates the high quality
      rating despite the current savings measures. The KTQ certification procedure
      offers hospitals the chance to obtain a systematic and comprehensive profile of
      the strengths and weaknesses in patient management and thereby establishes
      priorities for the employment of personnel for future projects. The certificate,
      recognized by the societies of the KTQ, provides documentation of a practicing
      "quality management established within the institution", which, according to
      section 137 and section 108 (SGBV), is legally binding. By means of the KTQ
      quality report the hospital fulfills the legally mandatory requirements in effect
      as of 2005 for the publication of quality reports according to section 137 SGVB.
      Further establishment of the KTQ certification procedure is likely because of its
      continuing evaluation and development, its multiple benefits as well as its
      acceptance by the City of Cologne Hospitals Inc.

PMID- 15966444
TI  - [Institute for Quality and Efficiency in Health Care. Goals and tasks].

PMID- 15966445
TI  - [Donepezil in patients with Alzheimer's disease--a critical appraisal of the
      AD2000 study].
AB  - The AD2000 study was a randomized placebo-controlled trial, the effects of
      donepezil, a cholinesterase inhibitor, in patients with Alzheimer's disease. It
      was the first long-term RCT not sponsored by the pharmaceutical industry. The
      study did not show any significant effect on patient-relevant outcomes. However,
      donepezil had a significant effect on cognitive scores. More patients taking
      donepezil stopped treatment due to adverse events, even when taking only 5 mg
      once daily. There are major concerns regarding the conduction of the AD2000 study
      as well as the presentation of the results. Much less patients than previously
      planned have been recruited, resulting in a low statistical power to detect a
      significant difference between both treatments. In addition, no true intention-to
      treat analysis based on the first randomization is presented. The validity of the
      AD2000 trial has to be questioned. However, there is still insufficient evidence
      to support the claim that cholinesterase inhibitors have beneficial effects on
      patient-relevant outcomes in patients with Alzheimer's disease. The change of
      cognitive performance as measured by different scales does not necessarily
      correspond to substantial changes in patient-relevant outcomes. In conclusion,
      the widespread use of cholinesterase inhibitors in patients with Alzheimer's
      disease is not supported by current evidence. Long-term-randomized controlled
      trials focusing on patient-relevant outcomes instead of cognitive scores are
      urgently needed.

PMID- 15966446
TI  - [Successful treatment of a severe case of idiopathic pulmonary fibrosis with
      rapamycin].
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder
      of the lower respiratory tract. The main clinical feature is a progressive
      shortness of breath, particularly on exercise. An overproduction and deposition
      of collagen and a proliferation of mesenchymal cells are the histopathologic
      characteristics. Rapamycin is an immunosuppressive agent with antiproliferative
      effects on mesenchymal cells including fibroblasts. It was this rationale that
      prompted the authors to administer rapamycin in a case of rapidly progressive
      IPF. CASE REPORT: In a 73-year-old female with a 2-month history of IPF,
      treatment with steroids and interferon gamma-1b did not improve the detrimental
      clinical course. Treatment with rapamycin was started; subsequently, clinical
      condition and objective findings improved markedly within weeks. She is now under
      treatment for 18 months. CONCLUSION: The authors presume that partial remission
      is related to rapamycin which may be effective in blocking the progressive
      fibrosis and increased collagen synthesis thought to be pathophysiologically
      relevant in this disease. Further studies have to show whether rapamycin may be a
      treatment option in idiopathic pulmonary fibrosis.

PMID- 15966447
TI  - Nursing research: do we still need to be concerned?

PMID- 15966448
TI  - Specialist palliative care nursing - an oxymoron?

PMID- 15966449
TI  - Palliative care nursing in New Zealand, 10 years on: diversity, complexity and
      resilience.

PMID- 15966450
TI  - Palliative care response to HIV/AIDS in South Africa.

PMID- 15966451
TI  - Towards a culturally acceptable end-of-life survey questionnaire: a Bengali
      translation of VOICES.
AB  - AIM: To assess the cultural acceptability and appropriateness of an English end
      of-life survey questionnaire translated into Bengali for use in east London.
      STUDY DESIGN: Group discussions with informal carers (n=3 groups) and
      professionals (n = l1 group). SAMPLE AND SETTING: Informal carers within a
      Bengali-speaking community (n = 26) in east London participated in three groups
      discussions led by three community workers trained in interviewing procedures.
      These data were followed up with one group discussion with bilingual health and
      social care professionals (n = 6). ANALYSIS: Data subject to content analysis.
      RESULTS: Participants were supportive of the development of the translated
      questionnaire. However, attention should be paid to vocabulary, shared meanings,
      cultural equivalence and the ways people conceptualize health and illness, and
      death and dying. CONCLUSIONS: These findings, together with participants' views
      on the administration of the questionnaire, will prompt revisions to the research
      approach when targeting ethnic and cultural groups in the future.

PMID- 15966452
TI  - Paediatric palliative care in the UK: past, present and future.

PMID- 15966453
TI  - End-of-life challenges in residential aged care facilities: a case for a
      palliative approach to care.

PMID- 15966454
TI  - Palliative care in residential care facilities: a brief review.

PMID- 15966455
TI  - The Liverpool Care Pathway (LCP) influencing the UK national agenda on care of
      the dying.

PMID- 15966456
TI  - Incorporating palliative care into heart failure management: a new model of care.

PMID- 15966457
TI  - International Journal of Palliative Nursing.

PMID- 15966458
TI  - Help the hospices.

PMID- 15966459
TI  - Cancer care is facing many challenges throughout the world.

PMID- 15966460
TI  - How basic is palliative care? Further views.

PMID- 15966461
TI  - How basic is palliative care? The debate continues.

PMID- 15966462
TI  - Association between neuroleptic drug-induced extrapyramidal symptoms and dopamine
      D2-receptor polymorphisms in Japanese schizophrenic patients.
AB  - The aim of the present study is to examine the relationship between dopamine D2
      receptor gene (DRD2) polymorphisms (Taq1A, Taq1B, -141C Ins/Del) and the risk of
      extrapyramidal adverse effects (EPS), assessed according to the Drug-Induced
      Extra-Pyramidal Symptoms Scale (DIEPSS), or the maintenance dose of
      antipsychotics in schizophrenic patients. The DIEPSS score was significantly
      higher in patients bearing the -141C Del allele than in those without it. Taq1A
      and Taq1B restriction fragment length polymorphisms (RFLPs) did not significantly
      affect the DIEPSS score. On the other hand, maintenance doses of neuroleptics and
      antiparkinsonian drugs were significantly higher in patients with the B1 allele
      of Taq1B RFLP than in those without it, while the Taq1A RFLP and -141C Ins/Del
      polymorphisms were not significantly related to the maintenance doses. In
      conclusion, the risk of EPS may be increased in patients with the -141C Del
      allele of the DRD2 gene. In these patients, antipsychotics should be administered
      with caution.

PMID- 15966463
TI  - Levocetirizine in 1-2 year old children: pharmacokinetic and pharmacodynamic
      profile.
AB  - BACKGROUND: Levocetirizine is an antihistamine with high affinity and selectivity
      for H1-receptors, which exhibits an excellent benefit/risk ratio in the treatment
      of allergic rhinitis and urticaria. This is the first study performed with this
      drug in very young children. OBJECTIVE: The aim of this study was to confirm the
      intended regimen of levocetirizine (0.125 mg/kg twice a day) for further studies
      in children aged 12-24 months. MATERIAL AND METHODS: The
      pharmacokinetic/pharmacodynamic profile of levocetirizine was studied in 15
      toddlers suffering from recurrent cough and other allergy-related symptoms, aged
      20.7 +/- 3.7 months, and treated twice a day with 0.125 mg/kg for 90 days. A
      histamine-induced wheal and flare test (W&F) was performed prior to treatment.
      Blood was sampled at 1, 2, 4, 6, 9 and 12 hours after the first dose. Twelve
      hours after the evening dose on Days 3-6, and on day 90, a histamine-induced
      wheal and flare test was repeated and a blood sample was taken for trough value
      assessment. RESULTS: A peak plasma level of 286 +/- 68 ng/ml was observed after
      one hour. The elimination half-life was 4.1 +/- 0.7 hours, the apparent body
      clearance 1.05 +/- 0.10 ml/min/kg, and the apparent volume of distribution 0.37
      +/- 0.06 l/kg. Morning trough values at Days 3-6, and at Day 90 were respectively
      78 +/- 30 ng/ml and 110 +/- 86 ng/ml. The median inhibition of the wheal was 100%
      at Days 3-6, and Day 90. That of the flare was 99.6% at Days 3-6, and 98.9% at
      Day 90. The overall safety profile of this three-month open study was good.
      CONCLUSION: This first study with levocetirizine in children aged 12-24 months
      shows the adequate pharmacokinetic/pharmacodynamic profile and the good safety
      profile of 0.125 mg/kg levocetirizine given twice a day, which can be proposed
      for further studies in this age group.

PMID- 15966464
TI  - Multiple-dose pharmacokinetics, pharmacodynamics and tolerability of the oral
      ET(A) endothelin-receptor antagonist SPP301 in man.
AB  - BACKGROUND: SPP301 is a competitive antagonist of ET-1 with a high selectivity
      for the ET(A) receptor. The multiple-dose pharmacokinetics, pharmacodynamics,
      safety and tolerability of SPP301 were investigated in healthy male subjects.
      METHODS: In an ascending-dose, double-blind, placebo-controlled trial doses of 5,
      20, 40 and 60 mg SPP301 were given orally on Day 1 and, after a wash-out period
      of 48 hours, once daily for seven days. At regular intervals, blood pressure and
      pulse rate, plasma levels of ET-1, and of SPP301 and its hydroxymethyl metabolite
      as well as urinary excretion of the parent drug and its metabolite were
      determined. RESULTS: SPP301 was generally well-tolerated. With the higher doses
      asymptomatic and transient increases in liver transaminases were observed. No
      other clinically relevant effects of SPP301 on hematology, biochemistry or
      urinalysis parameters were observed. Vital signs, ECG parameters and physical
      examinations showed no time or treatment effect. The pharmacokinetics of SPP301
      and its hydroxymethyl metabolite (Ro 68-5925) were linear up to 40 mg SPP301.
      Steady state was reached after 3-4 days. The apparent terminal half-life of
      SPP301 and the metabolite was in the range of 7-10 hours after single and
      repeated doses. At the 60 mg dose level plasma concentrations of SPP301 decreased
      from the first to the last day of oral treatment. The average decreases in Cmax
      and AUC were 33% and 37%, respectively. Cmax and AUC of the metabolite amounted
      to about 4-6% of the values for SPP301 under single and repeated-dose conditions.
      Urinary excretion of SPP301 and of its metabolite were below 0.1% and 5%,
      respectively. CONCLUSION: SPP301 is quite well-tolerated, pharmacokinetics are
      linear and time-independent up to 40 mg multiple doses. Steady state is reached
      after 3-4 days. Urinary excretion of the unchanged drug plays a minor role in the
      elimination process of SPP301. ET-1 plasma concentrations increased about 1.5
      fold at 20 mg and all further doses.

PMID- 15966465
TI  - A pharmacodynamic model of the effects of controlled-onset extended-release
      verapamil on 24-hour ambulatory blood pressure.
AB  - OBJECTIVE: To formulate and evaluate a pharmacodynamic model that characterizes
      the effects of S-verapamil on the circadian 24-hour ambulatory blood pressure
      (ABP). METHODS: ABP was recorded in 19 hypertensive patients off drug, and
      following administration of the targeted dose of COER-V given once daily for at
      least 30 days. Blood samples were collected after the last dose for determination
      of the pharmacokinetic of S-verapamil. ABP vs. time was analyzed using a cosinor
      function, and the effects of S-verapamil on ABP were fitted using the
      pharmacodynamic model. RESULTS: COER-V decreased average systolic and diastolic
      blood pressures (mesors): baseline, 142 +/- 10 and 90 +/- 7; treated, 132 +/- 8.8
      and 83 +/- 6.6 mmHg, respectively (p < 0.001). COER-V had no effect on the
      amplitude, cycle or the time shift (acrophase). The mean +/- SD time to peak and
      maximal S-verapamil concentrations were 9.5 +/- 1.2 hours and 46.4 +/- 35.8
      ng/ml, respectively. Model estimates of the maximal inhibited systolic (Emax S),
      diastolic. (Emax D) pressures and C50 were 101 +/- 14 mmHg, 61 +/- 9.9 mmHg and
      32.9 +/- 22.8 ng/ml, respectively. The model fit of the data was satisfactory and
      parameter estimates were precise. CONCLUSIONS: The model may be useful to
      characterize the relationship between plasma concentrations of verapamil and the
      antihypertensive effects of the drug and may be suitable for characterizing the
      effect of drugs on biological functions displaying oscillatory behavior.

PMID- 15966466
TI  - Drug utilization and potentially inappropriate drug use in elderly residents of a
      community in Istanbul, Turkey.
AB  - OBJECTIVE: This study investigates drug utilization and estimates the prevalence
      of potentially inappropriate drug use in a Turkish population aged 70 years or
      older. MATERIAL AND METHODS: A cross-sectional study was carried out on a total
      of 1019 participants who accepted face-to-face questionnaires in home interviews
      in Istanbul. All medications used in the three weeks prior to the study were
      recorded. Some major risk factors that might influence the use of inappropriate
      medication such as socio-demographic characteristics and concomitant disease such
      as depression and dementia were also questioned. Inappropriate drug use was
      assessed using the Beers criteria. RESULTS: Among the 1019 participants, 903
      (88.6%) had been using at least one medication during the last three weeks. The
      average number of medications used was 2.9 +/- 2.0. The most frequently drugs
      used were cardiovascular drugs (39.9%), followed by analgesics/anti-inflammatory
      drugs (16.2%), vitamin/mineral preparations (10.6%) and central nervous system
      drugs (10.2%). Of the 1,019 participants, 9.8% were using one potentially
      inappropriate medication and one patient was using two inappropriate drugs. The
      most common of these drugs were reserpine (23.7%), dipyridamole (21.8%),
      antihistamines (14.8%), and benzodiazepines (10.9%). Only age and total number of
      medications were associated with potentially inappropriate drugs in the
      multivariate analysis. CONCLUSIONS: This study revealed that drug utilization and
      the prevalence of inappropriate medication use in the elderly were lower than in
      published reports from most developed countries. Furthermore, polypharmacy and
      higher age were the main risk factors for potentially inappropriate drug use in
      the elderly.

PMID- 15966467
TI  - Bioequivalence evaluation of two brands of glimepiride 4 mg tablets in healthy
      subjects.
AB  - OBJECTIVE: This paper describes a bioequivalence study with two oral glimepiride
      (4 mg) tablets formulations. The reference preparation was Solosa/Aventis
      Pharmaceuticals Inc., USA, and the test preparation was Glimepiride/Specifar,
      Athens, Greece. SUBJECTS, MATERIAL AND METHODS: The study design was open,
      randomized, two-period, two-sequence, two-treatment with crossover involving 24
      healthy male and female subjects. All subjects completed the study. Glimepiride
      plasma concentrations were measured utilizing a sensitive, reproducible and
      accurate HPLC method. Pharmacokinetic parameters used to assess bioequivalence
      were AUC(0_last), AUC(0-inf) for the extent of absorption and Cmax and tmax for
      the rate of absorption. Statistical evaluation of Cmax, AUC(0_last), and AUC(0
      inf) was done after semilogarithmic transformation using a two-way analysis of
      variance (ANOVA). Tmax values were tested using the distribution-free Hodges
      Lehman interval. RESULTS AND CONCLUSION: The parametric 90% confidence intervals
      for ratio T/R ranged from 90.60-108.00% (point estimate 98.90%) for AUC(0-last),
      90.70-107.90% (point estimate 98.90%) for AUC(0-inf) and 86.70-103.70% (point
      estimate 94.80%) for Cmax, respectively. Based on the results of tmax, Kel and
      t(1/2), there were no statistically significant differences and the two
      glimepiride preparations are equivalent with respect to rate and extent of
      absorption as defined by the European Union bioequivalence requirements.

PMID- 15966468
TI  - [Studies of labyrinthine cholesteatoma-related fistulas: report of 22 cases].
AB  - OBJECTIVE: To study the incidence, location, pre- and postoperative symptoms
      (hearing loss, tinnitus, vertigo, facial palsy), preoperative diagnostic imaging,
      and surgical treatment of labyrinthine fistulae (LF). DESIGN: Retrospective case
      review. PATIENTS: Twenty-two cases of LF over 382 mastoid operations performed in
      a 168-month period. MAIN OUTCOME MEASURES: Clinical, imaging, and surgical
      correlation of extensive fistulae and bone fistulae. RESULTS: LF prevalence was
      5.8%. The main primary symptoms were otorrhea and hypoacusis. Only four patients
      presented vertigo as their main complaint. All patients underwent preoperative
      computed tomographic (CT) scans and preoperative audiometry. LF diagnosis was
      made before surgery for 100% of patients on the basis of CT scan. A second
      fistula was, however, misdiagnosed by imaging in two patients. With respect to
      surgical technique, a canal wall down procedure was performed in 77% and a
      conservative procedure was performed in 23%. Fistula was located in the
      horizontal semicircular canal in 100% of cases, and in 9%, a second fistula was
      operatively diagnosed. In 91% of cases, the matrix was removed, whereas it was
      left in the course of a canal down procedure in 9%. With a follow-up of 5.7
      years, hearing remained unchanged in 80% of patients. CONCLUSIONS: Surgery with
      removal of the cholesteatoma matrix and sealing of the fistula with temporalis
      fascia is a safe procedure that can help preserve cochlear function. The choice
      of a canal down procedure would be influenced by cholesteatoma characteristics
      rather than by the finding of an LF.

PMID- 15966469
TI  - Surgical strategy for thyroid bed recurrence in patients with well-differentiated
      thyroid carcinoma.
AB  - BACKGROUND: Well-differentiated thyroid carcinoma (WTC) has a low but definite
      rate of recurrence. The majority of these occur locoregionally and present a
      significant diagnostic and management challenge. It is the aim of this article to
      convey the complexities associated with revision surgery involving the thyroid
      bed and to present sound surgical strategies to deal with this problem in a
      manner that minimizes morbidity, adheres to oncologic principles, and achieves
      appropriate cure rates. METHOD: Between 1992 and 2002, 14 patients with revision
      surgery involving the thyroid bed were identified and managed according to an
      algorithm taking into account clinical, biochemical, and radiologic indices. All
      underwent revision surgery, and we applied our technique of wide field exposure
      by horizontally sectioning all of the ipsi- or bilateral strap muscles. We use
      blunt dissection to identify the recurrent laryngeal nerves and parathyroid
      glands. RESULTS: There were six males and eight females, with a median age of 38
      years (range 23-62 years). The median time between procedures was 25 months
      (range 6-120 months). The diagnosis was established by clinical examination,
      thyroglobulin determination, and/or imaging. All were treated with surgery and
      postoperative iodine 131 (I131). The median follow-up was 6 months (range 2-48
      months). Complications included two cases of temporary recurrent laryngeal nerve
      palsy, two patients with permanent and two patients with temporary hypocalcemia,
      two cases of temporary chyle leaks, and one recurrence. One patient underwent a
      negative exploration. CONCLUSION: The management of infield recurrence of WTC
      presents both a diagnostic and a therapeutic challenge owing to the disparity in
      presentation, the complexity of the anatomy, and indistinct tissue planes. The
      optimal treatment of these patients is surgical resection and postoperative I131.
      This can be accomplished safely and with little morbidity. The key to this type
      of surgery is a sound and systematic approach.

PMID- 15966470
TI  - Optimal parameters for the clinical test of dynamic visual acuity in patients
      with a unilateral vestibular deficit.
AB  - OBJECTIVE: To determine the influence of frequency and direction of head movement
      and type of vision chart on the score of a clinical test of dynamic visual acuity
      (DVA). METHODS: The subjects were 31 healthy individuals (22 to 79 years old) and
      10 patients (19 to 70 years old) with a unilateral vestibular deficit owing to
      surgical resection of an acoustic neuroma. They read a Snellen or an E-chart
      while their head was passively moved +/- 20 degrees back and forth in the
      horizontal or vertical direction at one of four frequencies (0.5, 1.0, 1.5, and
      2.0 Hz). The DVA score was the difference in the number of lines on the vision
      chart that could be read with the head passively moved versus with the head
      immobile. RESULTS: Four healthy subjects had a low DVA score during horizontal
      head movements at the fastest frequency (2.0 Hz) with the Snellen chart. In
      patients, DVA scores significantly decreased as head movement frequency increased
      from 0.5 to 1.0 Hz and from 1.0 to 1.5 Hz, during horizontal and vertical
      movements, and with both vision charts (p < .001). The DVA scores of healthy
      subjects were more consistent across three trials with the E-chart than with the
      Snellen chart at 1.0 and 0.5 Hz (horizontal movements, p < .01) and at 1.5 and
      1.0 Hz (vertical movements, p < .01). CONCLUSIONS: This study provides new
      indications on the optimal parameters for the clinical test of DVA. From the
      results, it is recommended that DVA be tested during horizontal and vertical head
      movements at a frequency of 1.5 Hz with the E-chart.

PMID- 15966472
TI  - Functional outcomes after primary mandibular resection and reconstruction with
      the fibular free flap.
AB  - OBJECTIVE: This study examined prospectively the functional outcomes of a cohort
      of patients who have undergone mandibulectomy and primary fibular free flap
      reconstruction, with particular emphasis on longitudinal comparison of the
      preoperative function with that in the postoperative and post-radiation therapy
      time periods. METHODS: Speech and swallowing data were gathered at three
      evaluation times (preoperatively, pre-radiation therapy, and post-radiation
      therapy) for patients treated for oral cavity cancer with mandibular resection
      and reconstruction with a fibular free flap. Single words and sentences were
      recorded and analyzed for speech intelligibility. Modified barium swallows of
      liquid, pudding, and cookie consistencies were analyzed and graded for problems
      in the oral preparatory and oral phase according to the University of Chicago
      Center for Speech and Swallowing Disorders Oropharyngeal Mobility Data Form.
      RESULTS: There was no significant difference across any of the evaluation times
      for single-word or sentence intelligibility. The swallowing data showed no
      instances of post-treatment aspiration or laryngeal penetration. There were also
      no significant differences in any of the swallowing parameters across treatment
      times. CONCLUSIONS: Osteocutaneous fibular free flaps are an excellent
      reconstructive option for mandibular and floor of the mouth defects.

PMID- 15966471
TI  - Ear, nose, and throat manifestations of Sjogren's syndrome: retrospective review
      of a multidisciplinary clinic.
AB  - OBJECTIVE: To assess the otolaryngologic manifestations of Sogren's syndrome
      (SS). DESIGN: A retrospective case study. SETTING: The Toronto Hospital. METHOD:
      Case note review of 196 patients evaluated in a multidisciplinary clinic for this
      disease. Patients were retrospectively classified according to the revised
      international classification. MAIN OUTCOME MEASURES: The prevalence of subjective
      and objective audiologic and otorhinolaryngologic abnormalities. RESULTS: One
      hundred eleven patients were diagnosed with primary and 26 with secondary SS,
      leaving 60 with unclassified sicca syndrome. There was minimal otologic
      pathology. There was a mildly increased prevalence of sensorineural deafness in
      secondary SS (41-60 years, 36%; 61-80 years, 70%). Approximately 50% of patients
      in each group complained of nasal symptoms, but only 20% had abnormal findings on
      rhinoscopy. Similarly, 60 to 70% in each group complained of throat symptoms, but
      only 20% had abnormal findings on indirect laryngoscopy. Thirty-eight percent of
      primary patients had parotid gland symptoms, and 25% had abnormally swollen
      glands, with eight subsequently diagnosed with lymphoma. No patients in the other
      two groups had abnormal parotid glands. CONCLUSIONS: SS does not appear to be
      associated with increased otologic or audiologic disease, except perhaps in
      conjunction with systemic autoimmunity. Nose and throat symptoms are common in
      SS, but the complications of mucosal dryness on examination are unusual
      (approximately 20%). Primary SS can cause serious parotid morbidity secondary to
      inflammation and infection. There is also a significant risk of lymphomas that
      often present as parotid masses, necessitating long-term follow-up.

PMID- 15966473
TI  - Is mastoidectomy indispensable in cochlear implant surgery?
AB  - OBJECTIVE: To challenge the need for mastoidectomy in cochlear implant (CI)
      surgery by comparing the advantages and disadvantages of the classic technique
      for CI, the mastoidectomy posterior tympanotomy approach (MPTA), with the
      suprameatal approach (SMA), a nonmastoidectomy approach. STUDY DESIGN AND
      SETTING: A retrospective study of 290 patients who underwent cochlear
      implantation in our department between 1989 and 2002. One hundred fifty-seven of
      them underwent the MPTA and 133 underwent the SMA. The ability of the electrode
      to expand in the MPTA patients who were reoperated on was examined, as was the
      influence of mastoidectomy on the course of chronic secretory otitis media (SOM)
      in a group of 56 children who suffered from chronic SOM prior to implantation.
      RESULTS: In all 4 reoperated children, in whom the MPTA was used, the mastoid was
      completely closed by bony regrowth on the cortical portion of the mastoid and the
      mastoid cavity was obliterated. The electrode had been embedded in dense fibrous
      tissue and bony spicule, preventing electrode expansion. Mastoidectomy was found
      to have no influence on the course of chronic SOM. The rate of postoperative SOM
      was found to be equal in 40 children who were operated on using the MPTA compared
      with 16 operated on using the SMA. CONCLUSION: Using a nonmastoidectomy approach,
      such as the SMA, provides a wide exposure of the middle ear and promontory and
      thus enables a well-controlled cochleostomy site and safe insertion of the
      electrode into the cochlea. Mastoidectomy in CI surgery is not indispensable; it
      may cause more disadvantages than advantages.

PMID- 15966474
TI  - Reovirus salvage of squamous cell cancer-contaminated wounds.
AB  - PURPOSE: To assess the susceptibility of human squamous cell carcinoma to
      reovirus infection in vitro and in vivo using a murine model of cancer
      contaminated wounds. METHODS: The University of Michigan squamous carcinoma 22B
      cell line was cultured and inoculated with reovirus in vitro. The effect of the
      reovirus was assessed with microscopy and a standard 3-(4,5-dimethyl-2-thiazolyl)
      2,5-diphenyl-2H tetrazolium bromide (MTT) assay. We used the previously
      established cancer-contaminated wound SCID mouse model to test saline and
      reovirus irrigation in vivo. Fifty-five mice were used; 15 were controls, 20 had
      immediate irrigation, and 20 had delayed irrigation. Surgical sites were assessed
      for palpable tumour biweekly. RESULTS: The microscopy and MTT assay both showed
      evidence of reovirus-mediated squamous cancer cell lysis. The control mice grew
      palpable tumours in 80% of the wounds. Immediate irrigation with saline delayed
      the onset of palpable tumour and demonstrated a persistent reduction in the rate
      of development of palpable tumours (p = .004 compared with controls). This effect
      disappeared when the saline irrigation was delayed, resulting in a tumour
      development rate that was not significantly different from that of the control.
      Wounds that were irrigated with reovirus, both immediately and delayed, did not
      produce palpable tumour (p < .0005 when compared with controls). CONCLUSIONS: (1)
      The University of Michigan squamous cell carcinoma 22B cell line is susceptible
      to reovirus in vitro. (2) Immediate irrigation with saline resulted in a
      significant delay in clinically evident tumour growth and a reduction in the rate
      of tumour development in the SCID mouse model. (3) The reovirus irrigation
      resulted in a significant reduction of tumour development in both the immediate
      and delayed groups in the SCID mouse model. (4) The efficacy of the reovirus
      irrigation in the delayed group suggests that the major mechanism of action is
      through a selective and specific targeting of implanted cancer cells.

PMID- 15966475
TI  - Outcome survey of therapy with diode laser in patients with allergic rhinitis.
AB  - OBJECTIVE: To measure the outcome of treatment of allergic rhinitis with a diode
      laser in the contact mode. DESIGN: Prospective study. SETTING: Tertiary care
      centre. METHOD: Forty-two newly diagnosed patients participated in the study.
      MAIN OUTCOME MEASURES: After a follow-up of 1 year, we measured the result of
      treatment by an allergy outcome survey questionnaire in the 3 months, 6 months,
      and 1 year following the operation. RESULTS: Twenty-seven of 42 patients (64.3%)
      who replied filled out the questionnaire completely. The mean operation time took
      1 minute, 28 seconds per patient, no nasal packing was necessary, and no
      complications were observed. Statistical analysis revealed significant
      improvement in the symptom score 1 year after laser surgery. The outcome of laser
      surgery declines with time. CONCLUSION: Short-term results revealed that diode
      laser treatment of allergic rhinitis is a useful procedure that can be performed
      as outpatient surgery under local anesthesia. The short operation time and less
      discomfort provide other reasons for choosing this treatment for allergic
      rhinitis.

PMID- 15966476
TI  - Particle repositioning manoeuvre in benign paroxysmal positional vertigo: is it
      really safe?
AB  - OBJECTIVE: A prospective study to determine the safety of the particle
      repositioning manoeuvre (PRM) by analyzing the various complications of the
      procedure. SETTINGS: Outpatient Department of Otorhinolaryngology, Nehru
      Hospital, Chandigarh, India. METHODS: Thirty patients with the classic findings
      of benign paroxysmal positional vertigo (BPPV) were included in the study.
      Clinical symptoms prior to the procedure were noted. Twenty-nine of them were
      subjected to PRM, and postprocedural instructions were given to all patients.
      Various side effects during and following the procedure were recorded. They were
      classified into early and late based on the period and into major and minor based
      on severity. All patients were reviewed after 3 days, 7 days, and 1 month.
      RESULTS: Of the 29 patients, 19 patients (65.52%) had heaviness in the head, with
      11 each (37.93%) reporting nausea and imbalance and 9 (31.03%) reporting
      instability during the procedure. A major complication, asystole, was noted in
      one patient. The percentage of side effects remained more or less the same in the
      early phase following the procedure. Only 5 of 29 patients were entirely
      asymptomatic. Ninety percent were relieved of symptoms by the end of 7 days, with
      no major complication recorded. CONCLUSIONS: PRM is an easy, effective, and
      relatively safe procedure. The risk of major complications with PRM, such as
      arrhythmias and asystole, highlights the need to consider other management
      modalities for BPPV in certain medically unfit patients.

PMID- 15966477
TI  - Inferior turbinate arterial supply: histologic analysis and clinical
      implications.
AB  - OBJECTIVE: To study the arterial architecture of the normal inferior turbinate.
      DESIGN: A prospective, nonrandomized, histologic study. MAIN OUTCOME MEASURES:
      Fourteen samples were removed at autopsy and during septoplasty operations,
      processed in the usual manner, stained with hematoxylin-eosin, and investigated
      microscopically. The analysis included data on the number, location within or
      outside the bone, the mean area, wall thickness, and distance the arteries
      traverse from the point of entrance into the bone to the point of exit into the
      soft tissue. RESULTS: One to three arteries enter the inferior turbinate
      posteriorly. In 7 of 14 inferior turbinates (50%), the arteries lie within the
      bone and in 2 (14%) within the soft tissue, and in 5 (36%), a mixed pattern was
      observed. The arteries run along a mean of 1.2 +/- 0.49 cm before piercing the
      bone into the soft tissue and split off to one to six branches. The mean area and
      the mean wall thickness of the arteries at the entrance into the bone posteriorly
      were significantly greater than that of the arteries emerging from the bone and
      entering the soft tissue anteriorly (0.099 +/- 0.056 mm2 vs 0.051 +/- 0.022 mm2
      [p < .01] and 0.116 +/- 0.042 mm vs 0.083 +/- 0.031 mm [p < .05], respectively).
      The inferior mucosal layer lacks major arteries. CONCLUSION: Given the data
      presented here, the excision of the inferior mucosal layer and the anterior
      portion of the inferior turbinate bone distal to the point of arterial exit
      constitute a relatively low risk for postoperative arterial bleeding.

PMID- 15966478
TI  - Doppler ultrasonography of the vertebrobasilar circulation in patients with
      sudden sensorineural hearing loss.
AB  - BACKGROUND: The etiology of sudden sensorineural hearing loss (SSNHL) is still
      unclear and is most probably diverse. OBJECTIVE: To determine the relationship
      between vertebrobasilar circulation and hearing in patients with SSNHL treated
      with pentoxifylline. DESIGN: Case-control study of 32 consecutive patients with
      SSNHL. METHODS: Patients with onset of SSNHL within 72 hours were treated with
      pentoxifylline infusions for 10 days. Transcranial Doppler (TCD) ultrasonography
      of vertebrobasilar circulation and hearing levels were examined at the onset of
      SSNHL (before treatment), after 10 days of therapy, and after 3 months. MAIN
      OUTCOME MEASURES: Hearing levels and TCD ultrasonographic findings at the onset
      of SSNHL, after 10 days, and after 3 months. RESULTS: Patients with SSNHL had
      more frequent pathologic TCD ultrasonographic findings compared with a normal
      population. Thirteen patients with SSNHL had normal TCD ultrasonographic
      findings, eight had borderline findings, and six had pathologic findings, and in
      five patients, initially, pathologic TCD ultrasonographic findings improved
      during therapy. Patients with normal TCD ultrasonographic findings had an average
      hearing improvement of 17 dB, whereas patients with borderline and pathologic TCD
      ultrasonographic findings had 3 and 0 dB of average hearing improvement,
      respectively. The greatest improvement (28 dB) was noticed in patients who showed
      improvement in TCD ultrasonographic findings. CONCLUSION: Although the number of
      patients is small, our results led to the conclusion that SSNHL has vascular
      etiology, at least in some patients. Consequently, the therapy for SSNHL should
      depend on etiology; that is, vasoactive medications should be reserved for
      patients with supposed vascular etiology. TCD ultrasonography could have a role
      in the decision regarding the optimal treatment of SSNHL.

PMID- 15966479
TI  - Laryngeal amyloidosis.
AB  - Localized amyloidosis is characterized by the deposition of amyloid fibres in a
      particular site or organ system in the absence of systemic involvement. Patients
      with localized laryngeal amyloidosis usually present with long-standing
      hoarseness or dyspnea. The diagnosis is made by a high degree of suspicion on the
      basis of the history and a characteristic appearance on direct laryngoscopic
      examination. When such lesions are seen, an adequate deep punch biopsy should be
      obtained, and an experienced pathologist should be able to identify the lesion on
      routine staining. However, the slides should be stained with Congo red and
      examined with polarized light microscopy to establish the diagnosis. Following
      proper diagnosis and evaluation of the extent of disease, usually by computed
      tomographic scan, surgery is the treatment of choice. Preservation of the voice
      and airway should be the aim in all patients. Endoscopic carbon-dioxide laser
      excision of the mass should be the first line of therapy. Patients may require
      repeated removal of the amyloid deposits. The results of treatment are excellent.

PMID- 15966480
TI  - Early experience with image guidance in endoscopic transnasal drainage of
      periorbital abscesses.

PMID- 15966481
TI  - Carcinosarcoma of the submandibular salivary gland: clinical case and review of
      the literature.

PMID- 15966482
TI  - Laminated pedicled latissimus dorsi myocutaneous flap for single-stage
      reconstruction of a composite anterior neck and tracheal defect.

PMID- 15966483
TI  - Osseous metaplasia of a nasal polyp.

PMID- 15966484
TI  - [The online-consultation of the University Hospital Zurich].
AB  - Since August 1999 free medical Internet consultations are offered by the
      University Hospital Zurich. Overall 13,984 inquiries have been answered until
      December 2003. As of today an average of about 10 questions has been received per
      day. The users are predominantly between 20 and 50 years old and most of them
      show normal characteristics in terms of weight and size. The incoming questions
      refer to a wide variety of medical subjects and 53% of them have been asked by
      women. Frequently asked questions refer to topics like HIV, nutrition,
      vaccination as well as contraceptive methods. Intimate questions concerning e.g.
      sexual dysfunction disorder as well as changes on male genitals are also
      overrepresented. Therefore medical Internet consultation is characterised by low
      thresholds and is particularly well suited for the consultation of intimate and
      sensitive topics.

PMID- 15966485
TI  - [Barrett's esophagus: diagnosis and therapy].
AB  - Barrett's esophagus is usually diagnosed by the endoscopic and histological
      finding of columnar epithelium with intestinal metaplasia in the distal
      esophagus. The prevalence of Barrett's esophagus (long segment) is <2% in the
      general population and 3-5% in patients with chronic reflux symptoms. Barrett
      mucosa predisposes patients to adenocarcinoma that develops in approximately 0.5%
      of these patients per year (Barrett mucosa --> dysplasia --> cancer sequence).
      The incidence of esophageal adenocarcinoma over the past few decades; the present
      incidence, however, is still rather low and is reported to be approximately 4 and
      approximately 0.5 per 100,000 in males and females, respectively. The malignant
      potential of the Barrett mucosa increases with dysplastic changes. Guidelines for
      surveillance and therapy are based on the presence and the degree of dysplastic
      lesions. Long-term studies on cost-effectiveness of these guidelines are,
      however, still missing.

PMID- 15966486
TI  - [Sudden cardiac death: who benefits from an implantable defibrillator?].

PMID- 15966487
TI  - [Mid-foot pain after vacation in Spain].

PMID- 15966488
TI  - [Acute pneumococcal meningitis 3 1/2 years after skull base fracture].

PMID- 15966489
TI  - [Atypical abdominal cyst. Gastrointestinal stromal tumor (GIST)].

PMID- 15966490
TI  - [Sports medicine physician Wilhelm Knoll (1876-1958)--"always an outspoken
      physician of German ideas in Switzerland"].

PMID- 15966491
TI  - Nerve stimulation in regional anesthesia: theory and practice.
AB  - There is now an accumulation of extensive and varied experience with the use of
      electrical stimulation for verifying the close approximation of needle and nerve,
      and for increasing the corresponding success rate. The application of this
      experience has been of proven benefit in the teaching of regional anesthetic
      techniques, in the performing of difficult nerve blocks, and in the use of novel
      accesses, resulting in decreased morbidity and a reduced requirement for local
      anesthetic. Nerve stimulation can also be used in uncooperative patients and in
      anesthetized individuals or patients under the effects of CNS depressors,
      although the risk of intraneural injection of local anesthetic is not eliminated
      in such cases. Putting the accummulated knowledge into practice is not simply a
      question of using electrical stimulation to elicite an artificial muscle
      contraction. Sound knowledge of the anatomy of the area to be blocked, the muscle
      territory subsidiary to the nerve in question, the applied neurophysiology, and
      the pharmacology of the local anesthetic used are needed. This chapter reviews
      the most important aspects, from nerve anatomy and physiology, to electrical
      features of the needle, and devices used for the updated clinical application of
      nerve stimulation in the practice of plexus regional anesthesia.

PMID- 15966492
TI  - Ultrasonography in the current practice of regional anaesthesia.
AB  - Ultrasound imaging techniques in regional anaesthesia are becoming a subject of
      major interest. The quality of blocks and analgesia is relevant to the
      perioperative outcome of patients and the development of perfect blocks has
      always been a focus in regional anaesthesia research. Several studies in
      neuroaxial anaesthesia and peripheral blocks have found that puncture processing
      performed under ultrasound guidance is easier and more effective than that
      performed without such guidance, thus ultrasound imaging techniques are being
      developed for clinical practice. One of the major advantages of these techniques
      is that they provide the opportunity to show the patient the anatomical situation
      before the puncture--using a near harmless and effective technique. A second
      advantage is that the puncture process and the application of medication can be
      demonstrated and clearly observed during the performance. If there is a problem
      with the spread or the application, the processing of the block can be
      immediately modified to improve the quality of the technique.

PMID- 15966493
TI  - Update in thoracic epidural anaesthesia.
AB  - Thoracic epidural analgesia (TEA) provides optimal perioperative anaesthesia and
      analgesia after thoracic and major abdominal surgery and decreases postoperative
      morbidity and mortality, mainly by blocking sympathetic nerve fibres. Surgery
      leads to a stress response characterized by sympathetic arousal, altered balance
      of catabolic and anabolic hormones, hypermetabolism, negative protein economy,
      and altered carbohydrate metabolism and immune function. A threefold increase of
      the plasma level of norepinephrine (noradrenaline) was detected up to 24 hours
      after surgery. These elevated catecholamine plasma levels are a risk, especially
      to patients with coronary artery disease, because unlike healthy coronary
      arteries, the stress response causes a vasoconstriction in arteriosclerotic
      coronary arteries. TEA results in a vasodilation in stenotic coronary arteries.
      In patients with instable angina pectoris, TEA reduced the number as well as the
      duration of episodes of cardiac ischaemia. Furthermore, TEA improves myocardial
      structure and function after coronary artery bypass grafting. Plasma levels of
      troponin T and I, as well as of atrial natriuretic peptides, were reduced and
      echocardiographic parameters of the ventricular wall motion were improved by TEA.
      Patients showed fewer arrhythmic episodes and postoperative myocardial
      infarction, and could be extubated earlier. The positive effects of TEA after
      coronary artery bypass grafting are not limited to a short postoperative period,
      the 2-year mortality rate also seems to be reduced. Optimized pain control and
      early mobilization decrease the riskof pulmonary complications, resulting in a
      shortened stay in intensive care units. In combination with early enteral
      nutrition, TEA leads to an earlier return of gastrointestinal function. Patients
      treated with thoracic epidural anaesthesia and analgesia have a better health
      related quality of life.

PMID- 15966494
TI  - Advances in ophthalmic regional anaesthesia.
AB  - Although retrobulbar and peribulbar regional anaesthetic techniques are used (by
      both anaesthesiologists and ophthalmologists) in various types of eye surgery,
      topical anaesthesia of the conjunctiva and cornea, followed--as needed--by sub
      Tenon's block, is now common in routine cataract surgery. Intracameral
      administration of local anaesthetic by the ophthalmologist is also performed.
      Sedation during ophthalmic surgery is distinctly lighter than for other surgery
      because it is essential that the patient remains alert and can cooperate with the
      surgeon. Continuous insufflation of oxygen-enriched air is needed to ascertain
      that CO2 has been flushed away. With a catheter placed into the nostril, the
      patient (whose head is draped and 'hidden') can have the end-tidal CO2 monitored.
      Finger index (FI), a palpation method that assesses the ease of performing
      retrobulbar block, is introduced. Because of the risk of life-threatening
      complications in ophthalmic regional anaesthesia, the services of an
      anaesthesiologist must be available and training of anaesthesia residents in
      ophthalmic regional anaesthesia is highly recommended.

PMID- 15966495
TI  - Advantages and disadvantages of adrenaline in regional anaesthesia.
AB  - Adrenaline has been added to local anaesthetic solutions for more than a century.
      The aim has been to delay the absorption of the local anaesthetic drug and to
      prolong and enhance its anaesthetic effect, both in peripheral and central
      neuraxial blockades. The intention in this chapter has been to give up-to-date
      knowledge about adrenaline as an adjuvant to local anaesthetics and/or opioids in
      clinical peripheral and central blockades. My own research has focused on
      optimizing postoperative epidural analgesia by adding adrenaline and/or fentanyl
      to an epidural mixture with dilute bupivacaine or ropivacaine. The main part of
      this chapter will therefore focus on the advantages and disadvantages of
      adrenaline in epidural analgesia. However, recent knowledge about adrenaline in
      peripheral blockade will also be covered, together with some pharmaceutical
      comments on the shelf-life of local anaesthetic mixtures containing adrenaline.

PMID- 15966496
TI  - Bupivacaine, levobupivacaine and ropivacaine: are they clinically different?
AB  - Two new, long-acting local anaesthetics have been developed after the evidence of
      bupivacaine-related severe toxicity: levobupivacaine and ropivacaine. Both these
      agents are pure left-isomers and, based on their three-dimensional structure,
      they have less toxic potential both on the central nervous system and on the
      heart. Several clinical studies have evaluated their toxicology and clinical
      profiles: theoretically and experimentally, some differences can be seen, but the
      reflections of these characteristics into clinical practice have not been
      evident. Evaluating randomised, controlled trials that have compared these three
      local anaesthetics, this chapter supports the evidence that both levobupivacaine
      and ropivacaine have a clinical profile similar to that of racemic bupivacaine,
      and that the minimal differences observed between the three agents are mainly
      related to the slightly different anaesthetic potency, with racemic
      bupivacaine>levobupivacaine>ropivacaine. However, the reduced toxic potential of
      the two pure left-isomers supports their use in those clinical situations in
      which the risk of systemic toxicity related to either overdosing or unwanted
      intravascular injection is high, such as during epidural or peripheral nerve
      blocks.

PMID- 15966497
TI  - The pharmacokinetics of ropivacaine in hepatic and renal insufficiency.
AB  - In patients with chronic end-stage liver disease, the peak plasma concentrations
      of ropivacaine after a single intravenous ropivacaine dose are similar to those
      in healthy subjects. However, patients with end-stage liver disease have about a
      60% lower mean ropivacaine clearance than healthy subjects and are thus expected
      to have over two-fold higher steady-state ropivacaine plasma concentrations
      during a continuous ropivacaine infusion. The peak plasma concentrations of
      ropivacaine after an axillary plexus block in uraemic patients are considerably
      higher than those in non-uraemic patients. However, uraemic patients have
      significantly higher alpha-1-acid glycoprotein plasma concentrations than non
      uraemic patients, and the peak plasma concentrations of free ropivacaine (related
      to toxicity) are similar in both groups. The pharmacokinetics of intravenously
      administered ropivacaine in patients with renal insufficiency and the possibility
      of clinically significant (S)-2',6'-pipecoloxylidide metabolite accumulation
      during continuous or repeated ropivacaine administration in these patients remain
      to be clarified.

PMID- 15966498
TI  - Local anaesthesia for pain relief after laparoscopic cholecystectomy--a
      systematic review.
AB  - Local anaesthetics (LA) are increasingly being used intraoperatively for the
      prevention of postoperative pain. The efficacy of local anaesthetic infiltration
      into incision sites has only been shown in patients undergoing inguinal
      herniorrhaphy. However, in one meta-analysis of the literature, intraperitoneal
      LA have been shown to be effective for pain relief following laparoscopic
      cholecystectomy (LC). The present review of the literature was done to summarise
      current knowledge on the effects of LA following LC. The Medline database was
      searched via PubMed to identify relevant randomised clinical trials in patients
      undergoing LC and where LA was used for pain management. The literature was
      restricted to adults (> 19 years) and humans. Abstracts of all articles were
      searched to determine if the trial was a comparison between LA and placebo
      injected intraperitoneally or infiltrated locally, with relevant postoperative
      data on pain scores, analgesic consumption and side effects. A total of 31
      relevant studies were identified from which data could be extracted.
      Postoperative pain, in general, was mild to moderate after LC, worst at the
      incision site or intra-abdominally. Five of six studies in which LA were injected
      locally found beneficial effects on postoperative pain but not analgesic
      consumption for up to 24 hours postoperatively. When injected intraperitoneally,
      14 of 23 studies found a reduction in pain scores in the LA group but only 9 of
      21 found a reduction in analgesic consumption. A meta-analysis of only three
      studies with extractable data found no difference in abdominal pain during 0-24
      hours between the LA and placebo groups. Side effects were few but some studies
      reported toxic plasma concentrations of LA in some patients, although no symptoms
      of LA toxicity were seen in these patients. In conclusion, LA have some
      beneficial effects when infiltrated locally and intraperitoneally. Although side
      effects are rare, the dose of LA should be monitored closely to avoid toxicity.
      Future studies should be directed towards determining whether the analgesic
      effects of LA are via peripheral mechanisms or systemic absorption. The
      explanation for the wide interindividual variation in pain following LC should
      also be better investigated.

PMID- 15966499
TI  - Clinical pharmacology and the use of articaine for local and regional
      anaesthesia.
AB  - Quicker onset and shorter elimination time favours (+/-) articaine as a short
      acting local anaesthetic for regional anaesthesia in day-case settings, e.g.
      arthroscopy (shoulder, knee), hand and foot surgery, and dentistry, because
      patients treated with articaine will be 'drug free' more quickly than those who
      receive other local anaesthetics. Articaine diffuses better through soft tissue
      and bone than other local anaesthetics. The concentration of articaine in the
      alveolus of a tooth in the upper jaw after extraction was about 100 times higher
      than that in systemic circulation. Articaine is metabolised via hydrolysis into
      articainic acid, 75% of which in turn is excreted as such and 25% in the
      glucuronidated form by the kidneys. The half-lives of elimination (t1/2alpha and
      t1/2beta) of articaine are 0.6 and 2.5 hours, whereas the apparent half-life of
      the metabolite articainic acid is 2.5 hours. Intrinsic half-lives of articainic
      acid are: t1/2alpha 12 minutes, and t1/2beta 64 minutes (1 hour). In dentistry,
      articaine is the drug of choice in the vast majority of literature. In other
      regional anaesthesia techniques (intravenous regional anaesthesia, epidural,
      spinal and plexus blocks) there are not enough data to prove that (+/-) articaine
      is safer and more effective than the short-acting local anaesthetics lidocaine,
      (+/-) prilocaine or (+/-) mepivacaine.

PMID- 15966500
TI  - Continuous peripheral nerve blocks in children.
AB  - In recent years, regional anaesthesia in children has generated increasing
      interest. Continuous peripheral nerve blocks have an important role in the
      anaesthetic arsenal, allowing effective, safe and prolonged postoperative pain
      management. Indications for continuous peripheral nerve blocks depend on
      benefits/risks analysis of each technique for each patient. The indications
      include surgery associated with intense postoperative pain, surgery requiring
      painful physical therapy, and complex regional pain syndrome. Continuous
      peripheral nerve blocks are usually performed under general anaesthesia or
      sedation, and require appropriate equipment in order to decrease the risk of
      nerve injury. New techniques, such as transcutaneous stimulation or ultrasound
      guidance, appear to facilitate nerve and plexus identification in paediatric
      patients. Nevertheless, continuous peripheral nerve block may mask compartment
      syndrome in certain surgical procedure or trauma. Finally, ropivacaine appears to
      be the best local anaesthetic for continuous peripheral nerve blocks in children,
      requiring low flow rate with low concentration of the local anaesthetic.

PMID- 15966501
TI  - The interaction of plasma renin activity and plasma atrial natriuretic peptide in
      21-hydroxylase deficiency patients.
AB  - Plasma renin activity (PRA) determination is the main index used to evaluate the
      mineralocorticoid control in 21-hydroxylase deficiency (21-OHD). PRA values
      within or at the upper limit of the age-appropriate range, or values <5 or 10
      ng/ml/h have been regarded as adequate control. Atrial natriuretic peptide (ANP)
      has opposite actions to those of angiotensin II/aldosterone, and could help to
      understand the hydrosaline homeostasis in 21-OHD. We studied the interaction
      between PRA and ANP levels in 10 controls and 26 patients with 21-OHD under
      corticoid treatment. Patients were divided into two groups according to PRA
      levels, < or > or = 5 ng/ml/h, irrespective of the clinical form of 21-OHD. Blood
      samples for determination of PRA and ANP levels were taken after 30 min in the
      sitting position (basal), after 30 min in the recumbent position and after 15 min
      of 20 degrees head-down tilting. ANP levels (pg/ml) in the basal, supine and
      after head-down tilting position were 25.9 +/- 1.6, 42.7 +/- 7.4 and 54.3 +/- 5.5
      in controls; 28.5 +/- 2.1, 38.3 +/- 2.1 and 48.8 +/- 4.1 in the group with PRA
      levels <5 ng/ml/h, and 20.9 +/- 1.9, 26.6 +/- 2.5 and 34.6 +/- 3.1 in the group
      with PRA levels > or = 5 ng/ml/h, respectively. Basal and after head-down tilting
      ANP plasma levels were similar between the controls and the group with PRA levels
      <5 ng/ml/h. However, the group of patients with PRA levels > or = 5 ng/ml/h
      showed lower basal and stimulated ANP levels compared to the control group
      (p<0.05). The decreased plasma ANP levels in the basal condition and after head
      down tilting indicate a chronic contraction of the extracellular volume in 21-OHD
      patients with increased PRA levels. Therefore, mineralocorticoid deficiency is
      counteracted by decreased ANP secretion in order to preserve fluid and
      electrolyte homeostasis.

PMID- 15966502
TI  - Effect of hormone therapy on the elastic properties of the arteries in healthy
      postmenopausal women.
AB  - The aim of the study was to assess the effect of continuous hormone therapy (HT)
      for 1 yr on pulse wave analysis and central aortic pressure in healthy
      postmenopausal women. Sixty-five healthy postmenopausal women were randomly
      allocated to receive either conjugated equine estrogens 0.625 mg plus
      medroxyprogesterone acetate 5 mg (CEE/MPA, Premelle 5, Wyeth-Ayerst Lab,
      Philadelphia, PA, no.=32) or no therapy (no.=33). Treatment was continuous, and
      the study period lasted 12 months. Central aortic pressure, augmentation and
      augmentation index (AI) were determined non-invasively using applanation
      tonometry. All measurements were performed at baseline and at the end of the
      study by the same person. Ns differences were found between baseline values and
      values at the end of the study in either the control or the CEE/MPA group in
      central systolic aortic pressure (107.0 +/- 13.1 vs 107.6 +/- 11.3 mmHg, p=0.80,
      and 110.8 +/- 10.8 vs 112.3 +/- 11.4 mmHg, p=0.23, respectively), augmentation
      (12.6 +/- 4.2 vs 11.9 +/- 4.8 mmHg, p=0.45 and 11.7 +/- 3.7 vs 12.6 +/- 4.2 mmHg,
      p=0.34, respectively), and percentage of AI (36.8 +/- 9.3 vs 36.3 +/- 10.3,
      p=0.81 and 34.1 +/- 8.9 vs 34.9 +/- 9.8, p=0.72, respectively). The results of
      this preliminary report suggest that HT for 1 yr does not have any significant
      effect on central aortic pressure and wave reflection in healthy postmenopausal
      women.

PMID- 15966503
TI  - Association between bone mineral density and polymorphisms of the VDR, ERalpha,
      COL1A1 and CTR genes in Spanish postmenopausal women.
AB  - Bone mineral density (BMD), the major determinant of osteoporotic fracture risk,
      has a strong genetic component, and several candidate gene polymorphisms have
      been implicated in the regulation of this process. In view of the reported
      associations between the BMD and polymorphisms in the collagen type I alpha 1
      gene (COL1A1), vitamin D receptor (VDR), estrogen receptor (ER)alpha and
      calcitonin receptor (CTR) genes, an association study was performed between VDR,
      COL1A1, CTR and ER genotypes and lumbar spine, femoral neck and Ward's triangle
      BMD in postmenopausal Spanish women. We statistically controlled for many
      confounding factors, such as height, weight, age, years since menopause, use of
      hormone replacement therapy (HRT), tobacco consumption, use of oral
      contraceptives, calcium dietary intake or exercise practice. No association
      between COL1A1 or ER genotypes and BMD was detected. However, we described a
      statistically significant association between a personal history of fractures and
      COL1A1 genotype. The ss genotype was found to be over-represented between those
      women who had a personal history of fractures. The analyses of the VDR
      polymorphisms showed that FF subjects reached the highest values of BMD at the
      three measured sites, whereas Ff individuals had an intermediate BMD and ff women
      had the lowest values. However, the VDR-BsmI gene polymorphism was not found to
      be associated with adjusted BMD. For the CTR polymorphisms, our study showed that
      women with the aa genotype had a lower adjusted BMD at the femoral neck. In
      conclusion, in our postmenopausal Spanish women cohort we found a statistically
      significant association beteween the VDR and CTR gene polymorphisms and the BMD.
      However, we did not find any association between the ER and COL1A1 gene and the
      BMD. The COL1A1 gene was found to be associated with the prevalence of
      osteoporotic fractures. Of all the studied gene polymorphisms, the FokI VDR gene
      polymorphism seems to be the strongest BMD genetic determinant of postmenopausal
      Spanish women.

PMID- 15966504
TI  - Effects of pregnancy and lactation on bone mineral density, and their relation to
      the serum calcium, phosphorus, calcitonin and parathyroid hormone levels in rats.
AB  - The aim of this study was to evaluate the net changes in bone mineral density
      (BMD) during the reproductive cycle, and their relation with changes in serum
      calcium (Ca), phosphorus (P), PTH and calcitonin levels in rats. Twenty-seven
      female Wistar rats were included in this study. They were divided into three
      groups as pregnant, lactating and control groups. BMDs of lumbar vertebrates,
      femoral and tibial bones, and Ca, P, calcitonin and PTH levels were measured at
      the end of pregnancy, at the end of lactation and in nulliparous controls. In the
      pregnant group, the BMDs of rats were significantly higher in lumbar vertebrates,
      femoral and tibia bones than those of the control group (p<0.05). Their PTH and
      Ca levels were significantly lower than the control group (p<0.05). However, no
      statistically significant difference was found regarding P and calcitonin levels
      when compared to those of the control group. In the lactating group, the BMDs
      were significantly lower in lumbar vertebrates, femoral and tibia bones than
      those seen in the control and pregnant groups (p<0.05). Ca and PTH levels were
      significantly higher in lactating rats than in those of pregnant rats (p<0.005).
      Normal pregnancy increases BMD in rats, whereas lactation decreases it. Change in
      PTH levels is supposed to contribute to the mineralization and demineralization
      of the skeleton during pregnancy and lactation, respectively.

PMID- 15966505
TI  - Results and long-term follow-up after unilateral adrenalectomy for ACTH
      independent hypercortisolism in a series of fifty patients.
AB  - Untreated hypercortisolism is a fatal state, causing functional disability. Even
      after successful treatment, clinical recovery is slower than the biochemical one,
      but data about clinical results, well-being and working capacity after surgery
      are scarce. This retrospective study aimed at evaluating the long-term outcome of
      patients after adrenalectomy for ACTH-independent hypercortisolism by the
      analysis of the clinical results, the survival and the subjective well-being
      status after surgery. Clinical data in 50 patients suffering from ACTH
      independent hypercortisolism and treated between 1980 and 2000 by unilateral
      adrenalectomy were recorded. At a mean follow-up of 134 months, 3 patients were
      dead. All the surviving patients were asked to self estimate the physical and
      psychological recovery after surgery. After surgery, 100% of patients were
      biochemically cured. A clinical recovery was observed in most cases: obesity in
      59.6% and hypertension in 57.5%. Bone mass density (BMD) significantly improved
      (+20%). The long-term mortality rate did not differ from normal population.
      Subjectively, a full recovery was confirmed by 95.6% of the surviving patients;
      it was correlated with the subjective feeling of physical recovery (95.6%) and
      regained working ability (93.3%). Despite of biochemical and clinical cure, no
      subjective improvement of the psychological conditions was observed in 26.7% of
      cases. At long-term follow-up, most objective symptoms of Cushing's syndrome (CS)
      disappear; subjective health and working ability are often regained, but a
      psychological impairment could persist in spite of a successful treatment.

PMID- 15966506
TI  - Aminotransferase and gamma-glutamyltranspeptidase levels in obesity are
      associated with insulin resistance and the metabolic syndrome.
AB  - Fatty liver at ultrasounds, with/ without raised plasma levels of hepatic
      enzymes, is common in obesity. In most cases, it is the hallmark of non-alcoholic
      fatty liver disease (NAFLD), a potentially progressive disease associated with
      insulin resistance and the metabolic syndrome (MS). We tested the hypothesis that
      insulin resistance per se might be associated with hepatocellular necrosis.
      Alanine and aspartate aminotransferases (ALT and AST; no.=799) and gamma
      glutamyltranspeptidase (GGT; no.=459) were analyzed in a group of treatment
      seeking obese patients recruited in 12 Italian medical centers. Insulin
      resistance was calculated by the homeostasis model assessment method (HOMA-IR;
      no.=522). Median ALT and AST increased with increasing obesity class (p=0.001 and
      p=0.005) and exceeded normal limits in 21.0% of cases. Also HOMA-IR increased
      with the obesity class (p<0.0001), and was higher in subjects with elevated ALT
      (median, 4.93 vs 2.89; p<0.0001). A significant correlation was observed between
      HOMA-IR and ALT (R2=0.208; p<0.0001), as well as between HOMA-IR and AST or GGT
      (R2=0.112 and R2=0.080; p<0.0001). The correlation was maintained when cases with
      elevated enzyme levels were omitted from analysis. Diabetes and
      hypertriglyceridemia were the features of the MS most commonly associated with
      raised liver enzymes. In logistic regression, after correction for age, gender,
      BMI and features of the MS, HOMA-IR maintained a highly predictive value for
      raised ALT, AST and GGT. We conclude that in obesity insulin resistance is a risk
      factor for raised liver enzyme levels, possibly related to NAFLD.

PMID- 15966507
TI  - Spontaneous lymphocyt ic thyroiditis in interferon regulatory factor-1 deficient
      non-obese diabetic mice.
AB  - Interferon regulatory factor-1 (IRF-1) is a transcription factor involved in
      interferon-mediated immune reaction, CD8+ T cell differentiation and development
      of T helper 1 immune reaction. We have recently demonstrated that IRF-1 is
      pivotal in iodine-induced lymphocytic thyroiditis (LT) in non-obese diabetic
      (NOD) mice. However, it remains unclear whether the mechanism involved in
      spontaneous LT is identical with iodine-induced LT in NOD mice. To determine the
      role of IRF-1 in spontaneous LT, we used IRF-1 deficient NOD mice as well as IRF
      1 +/+ and +/- mice which were free from treatments for LT induction, and LT was
      evaluated at 24 weeks of age. IRF-1 +/+, +/- and -/- mice developed LT
      spontaneously, and there were no differences among the 3 IRF-1 genotypes in the
      incidence and severity of LT. Whereas both CD4+ and CD8+ T cells were present in
      the diseased thyroid of IRF-1 +/+ mice, CD8+ T cells were absent in the thyroid
      of IRF-1 -/- mice. MHC class II antigen expression was induced in the inflamed
      thyroid of IRF-1 -/- mice comparable to IRF-1 +/+ mice. There was a selective
      reduction in the number of CD8+ T cells in the spleen of IRF-1 -/- mice. IFNgamma
      production, but not IL-10, by concanavalin A-stimulated splenocytes was
      significantly reduced in IRF-1 deficient mice. These results suggest that IRF-1
      plays only a minor role in spontaneous LT in NOD mice and, furthermore, the
      mechanism involved in spontaneous LT is different from that of iodine-induced LT
      in NOD mice.

PMID- 15966508
TI  - Thyroid function differently affects serum cystatin C and creatinine
      concentrations.
AB  - Cystatin C (Cys C) is a cysteine protease inhibitor produced at a constant rate
      by nucleated cells, filtered through the glomerular membrane and reabsorbed by
      kidney tubular cells. Aim of this cross-sectional and longitudinal study was to
      assess serum Cys C and creatinine (Crea) concentrations in thyroid dysfunction.
      One hundred and eighty-one patients, 26 with untreated non-toxic nodular goiter,
      58 with hyperthyroidism, 31 on L-T4 suppressive therapy for non-toxic nodular
      goiter, 35 with short-term hypothyroidism after L-T4 withdrawal to perform whole
      body scan for thyroid cancer, 11 with long-term hypothyroidism due to chronic
      autoimmune thyroiditis and 20 patients with mild hypothyroidism were enrolled in
      the study. Fifty-seven age- and sex-matched normal subjects served as controls.
      Serum Cys C, Crea, free T4 (FT4), FT3 and TSH were assessed. Thirty hyperthyroid
      patients and 35 short-term hypothyroid patients were followed prospectively until
      euthyroidism was reached by methimazole or L-T4 therapy. The cross-sectional
      study showed that mean serum Crea concentrations were significantly reduced in
      overt hyperthyroid or subclinical hyperthyroid patients, while it was increased
      in overt hypothyroid patients, but not in mild hypothyroidism. Conversely, serum
      Cys C levels were significantly increased in overt hyperthyroid patients compared
      to controls (p<0.05), and significantly decreased in short-term, long-term and
      mild hypothyroids (p<0.05, p<0.05, p<0.01, respectively). However, 36 (62%)
      hyperthyroid patients and 50 (76%) hypothyroid patients had normal serum Cys C
      values. In the prospective study, restoration of euthyroidism by either
      methimazole or L-T4 therapy was associated with normalization of mean serum Cys C
      concentrations. In conclusion, thyroid dysfunction affects serum Cys C
      concentration, possibly influencing the production rate of the protein. However,
      the observation that hyper- or hypothyroid patients have normal serum Cys C
      levels limits its use as a marker of peripheral thyroid hormone effect.

PMID- 15966509
TI  - Adult height in sixty girls with Turner syndrome treated with growth hormone
      matched with an untreated group.
AB  - The main clinical feature of Turner syndrome (TS) is growth failure, with a mean
      spontaneous adult height ranging between 136 and 147 cm, according to the
      specific curves of various populations. Though a classical deficiency of GH has
      not been generally demonstrated, GH has been administered since 1980 in trials,
      using replacement doses just initially, with a subsequent trend to increase it.
      We report the outcome of GH therapy given at the fixed dose of 0.33 mg/kg/week in
      60 TS girls observed until adult height; 59 untreated TS girls, matched for
      auxological, karyotypical characteristics and time of observation, born within
      the same decade served as controls to evaluate GH efficacy. The calculation of
      the gain in cm over PAH was performed on specific Italian Turner curves, as well
      as height evaluation as SD score and growth velocity. The same calculations were
      made using Lyon references and Tanner standards. The mean CA at the beginning of
      GH treatment was 10.9 +/- 2.76 yr (range 4.5-15.9). Mean adult height of treated
      group was 151 +/- 6.1 cm with a gain over the PAH calculated at start of therapy
      (142.9 +/- 5.3 cm) of 8.2 +/- 3.9 cm. Ns change was observed between the PAH at
      first observation (143.6 +/- 7.0 cm) and adult height (144.3 +/- 5.6 cm) in the
      control group. Treatment was well tolerated, no relevant side effects were
      observed, glucose metabolism resulted no more affected than in untreated
      subjects, IGF-I levels remained within 2 SD. Our results in 60 TS girls, though
      the dose remained unchanged throughout the treatment, show a good response,
      characterized by a striking variability in each patient (mean gain in cm over PAH
      at adult height of 8.17 +/- 3.9, range 3-21 cm), and significant also in
      comparison with the control group. As the chronological age at start of therapy
      ranged between 4.5 to 15.9 yr, the results were further evaluated dividing the
      patients into two groups, according to the age, < or >11 yr. Thirty girls were
      <11 yr (mean 8.7 +/- 1.76 yr) and 30 were >11 yr (mean 13.2 +/- 1.4 yr). The gain
      in cm over the PAH in each group was, respectively, 8.1 +/- 3.4 and 8.2 +/- 4.3
      cm without any significant difference between the two groups, showing no negative
      correlation between the CA at the beginning of GH and the response to treatment.

PMID- 15966510
TI  - Effects of sex steroids on expression of adenylyl cyclase messenger RNA in rat
      uterus.
AB  - The aim of our study was to investigate the effects of estradiol (E2) and/or
      progesterone (P4) bilateral ovariectomized rats on gene expressions of adenylyl
      cyclases (AC2, AC4, AC6, AC9). Non-pregnant (NP) Wister rats (between post-natal
      10 and 12 weeks) and normal pregnant rats (between postnatal 10 and 14 weeks)
      were used. NP rats were divided into five groups: 1) control NP rats, 2)
      ovariectomy rats (OVX), 3) OVX injected with E2 (6 microg) for 4 days (E2), 4)
      OVX injected with P4 (5 mg) for 4 days (P4), 5) ovariectomy rats injected with E2
      (6 microg) and P4 (5 mg) for 4 days (E2/P4). The ovariectomized rats were
      sacrificed by anesthesia of diethyl ether after 24 h from the last injection. The
      pregnant group was sacrificed in the same way on 14 (P14), 17 (P17) and 21 (P21)
      of pregnancy, because the days between P14 and P17 were the second trimester of
      pregnancy and P21 was the third trimester. Total RNA were prepared from the uteri
      of each subject, and expression of ACs was analyzed by reverse transcription
      polymerase chain reaction (RT-PCR). Expression of mRNAs for AC2, AC4, AC6 and AC9
      were maximally increased on P17 and then decreased on P21. In OVX rats,
      expression of mRNAs for AC2, AC4, and AC9 were decreased as compared to NP. AC2
      mRNA was significantly increased by E2 treatment. AC4 and AC9 mRNA was
      significantly increased by injection of E2 or P4. AC6 mRNA level was not affected
      by E2 and/or P4. In conclusion, AC2, AC4 and AC9 gene expression is affected by
      estrogen and/or P4. On the contrary, AC6 gene expression was not changed by OVX
      or hormone treatment. Since, all ACs mRNA examined here are increased during
      pregnancy, AC6 may be affected by other factor(s) other than estrogen and P4.

PMID- 15966511
TI  - Final height in short polytransfused thalassemia major patients treated with
      recombinant growth hormone.
AB  - We measured the final height (FH) of 25 short polytransfused thalassemia major
      (Th) patients (18 males) with a reduced GH reserve treated for 3.3 +/- 1.2 yr
      with recombinant GH (rhGH), 0.2 mg/kg/week sc. At baseline, all patients were
      clinically prepubertal; their chronological (CA) and bone ages (BA) were 13.6 +/-
      2.0 and 11.4 +/- 1.6 yr, respectively. In 9 out of 18 males and 5 out of 7
      females, the onset of puberty occurred spontaneously during the treatment. At the
      end of the rhGH administration, the height of the enrolled children was not
      significantly increased when calculated for CA (HxCA), while it was significantly
      decreased (p=0.004) when calculated for BA (HxBA); the BA increase (3.29 +/- 1.65
      yr) was significantly higher (p<0.001) than the height age increase (2.16 +/-
      0.98 yr). The FHxCA showed a significant increase (p=0.001) compared to both
      baseline and the end of therapy, while the FHxBA was significantly decreased
      (p<0.001) compared with the corresponding value at baseline. At the end of
      therapy, both HxCA and HxBA resulted positively related to the BA at baseline
      (r=0.50 and 0.42, p=0.012 and 0.034, respectively). FH was positively correlated
      with CA (r=0.63, p=0.001), BA (r=0.68, p<0.001) and HxBA (r=0.59, p=0.002)
      evaluated at baseline, and with both HxCA and HxBA (r=0.82 and 0.74,
      respectively, p<0.001), evaluated at the end of treatment. A negative correlation
      was found between FH and the length of treatment (r=-0.56, p=0.004). Our data
      seem to exclude that prolonged rhGH therapy could improve FH in Th patients; on
      the contrary, a negative effect may be hypothesized.

PMID- 15966512
TI  - A non-functioning pituitary adenoma initially mimicking a microprolactinoma: The
      case for long-term follow-up of patients with mild hyperprolactinemia?
AB  - OBJECTIVE: A correct differential diagnosis of patients with mild
      hyperprolactinemia is essential to select the most appropriate treatment
      modality. CLINICAL PRESENTATION: A 50-yr-old woman presented to our Department
      for evaluation of an intra- and suprasellar mass causing progressive visual
      defect. Mild hyperprolactinemia causing menstrual irregularities was diagnosed in
      February 1989. In 1992, serum PRL levels ranged from 50 to 70 microg/l and
      magnetic resonance imaging (MRI) of the hypothalamic-pituitary region showed the
      presence of a 7 mm microadenoma. Bromocriptine therapy resulted in normalization
      of PRL levels and menstrual cycle, while a repeat MRI showed no change. Menses
      stopped in March 1998, when the patient was 46 yr old. Subsequently, the patient
      complained of worsening headaches and, starting from July 2001, visual
      disturbances. In March 2002, MRI showed a large pituitary tumor, measuring
      40x37x28 mm. In May 2002, the patient was operated through the transsphenoidal
      approach with apparent total tumor removal. Histological examination confirmed a
      pituitary adenoma that stained negative for all pituitary hormones. Four months
      after surgery, the patient reported an improvement of visual function. MRI of the
      hypothalamic-pituitary region, performed 4, 13 and 25 months after surgery,
      showed a partially empty sella with no evidence of residual tumor. CONCLUSIONS:
      This case suggests that, to exclude the alternative diagnosis of nonfunctioning
      pituitary adenoma or another mass lesion of the hypothalamic-pituitary region,
      repeat neuroimaging studies during long-term follow-up may be advisable in
      patients with presumed microprolactinoma who did not show reduction of the tumor
      during dopaminergic therapy.

PMID- 15966513
TI  - Poorly differentiated small cell neuroendocrine carcinoma localized in three
      different endocrine glands: response to chemotherapy and octreotide LAR.
AB  - Neuroendocrine tumors represent a heterogeneous category of neoplasm, with
      conflicting diagnostic and therapeutic demands. We here describe the case of a 72
      yr-old woman with evidence of a poorly differentiated small-cell neuroendocrine
      carcinoma (NEC) localized in different endocrine glands and other non-endocrine
      organs. In particular, a large ovarian mass, multinodular thyroid goiter, right
      adrenal mass, cystic liver metastases and anterior mediastinum lymph node
      metastasis were present. The largest thyroid nodule caused tracheal restriction
      and dyspnea. Diagnosis of poorly differentiated metastasized NEC of unknown
      origin was made on the basis of histological and immunohistochemical findings,
      and treatment with etoposide (100 mg/m2 in days 1, 2 and 3) and cisplatinum (45
      mg/m2 in days 2 and 3) was initiated. Simultaneously, im administration of
      octreotide LAR 20 mg every 28 days was started, according to the presence of SS
      receptors at 111In-octreotide scan. Rapid improvement of dyspnea and a reduction
      of the largest thyroid nodule, liver metastases and adrenal mass by 50% were
      observed after 3 months of treatment; the dimensions remained stable thereafter,
      while the pericardial lymph node disappeared. In conclusion, poorly
      differentiated NEC of unknown primary site is a well-recognized category, usually
      with an aggressive behavior, rapid growth rate and wide dissemination. Median
      survival of these patients is 6 months if left untreated. Our patient is alive 18
      months after beginning the treatment, reporting good general condition and
      quality of life over the whole follow-up period.

PMID- 15966514
TI  - Resistance to thyroid hormone associated with autoimmune thyroid disease in a
      Turkish family.
AB  - The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired
      tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common
      thyroid autoimmune disease. We present a Turkish family with both RTH and
      Hashimoto's thyroiditis. RTH was detected through the presence of point mutation
      in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due
      to the presence of thyroid autoantibodies. The proposita, her affected mother as
      well as her unaffected sister have thyroid autoantibodies consistent with
      Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding
      the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both
      the proposita and the mother. The mutation is a replacement of cytosine for
      guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a
      normal proline with an alanine (P453A), which reduces the affinity for T3 to 17%
      of that of the normal TRbeta. Both also have modest elevation of serum TSH
      levels. In severe RTH, marked elevation of thyroid hormone concentrations in the
      absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when
      RTH is mild and associated with thyroiditis, even a modest thyroid gland
      insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This
      will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is
      then necessary to establish the diagnosis. In addition, under these
      circumstances, treatment with thyroid hormone should be considered.

PMID- 15966515
TI  - Multiple pulmonary neoplasia positive for thyroglobulin.
AB  - We present, for the first time, a case of carcinoid metastatic pulmonary tumor
      positive for thyroglobulin. A 73-yr-old woman diagnosed with metastases of
      probable thyroid carcinoma, manifested by a mediastinic mass and multiple
      pulmonary nodules positive for radioiodine (I131). Histological analysis showed
      typical findings of carcinoid tumor with positive immunohistochemistry for neuron
      specific enolase, synaptophysin and thyroglobulin, and negative for chromogranin
      and calcitonin. We underline the exceptional finding of positive reaction for
      thyroglobulin, and discuss difficulties in differential diagnosis between
      metastatic differentiated thyroid and carcinoid neoplasms.

PMID- 15966516
TI  - Pioglitazone treatment in Cushing's disease.

PMID- 15966517
TI  - High-flow priapism in testosterone-treated boys with constitutional delay of
      growth and puberty may occur even when very low doses are used.

PMID- 15966518
TI  - A postcard of a giant and his physician (collection W.W. de Herder).

PMID- 15966519
TI  - Myotomy length determinants in endoscopic staple-assisted
      esophagodiverticulostomy for small Zenker's diverticula.
AB  - A small Zenker's pouch is a major challenge for endoscopic staple-assisted
      esophagodiverticulostomy (ESED). This study tested the stapler dimensions so as
      to identify limitations they impose on ESED. Combining ESED with additional
      endoscopic suturing could extend the incision and consequently the myotomy.
      Zenker's diverticulum residual pouch measurements were performed with a
      previously reported latex glove model and in patients undergoing surgery. Two
      stapler designs were compared by measuring the residual pouch length for both the
      stock and modified staplers. One other stapler model cannot be modified without
      damaging the mechanism. The Endostitch was used to place an additional suture at
      the apex of the staple line, allowing cutting between the staples while leaving a
      closed distal incision. All three staplers suitable for ESED leave a residual
      pouch of 1.5 cm when unmodified. The modified anvil staplers gave a smaller
      residual pouch by 4 to 5 mm. An additional septal reduction can be accomplished
      by suturing the area distal to the staple line and incising the party wall beyond
      the stapler cut. The absolute amount of residual pouch with an additional myotomy
      is 3 mm. The combined staple-suture technique has proven relatively safe thus
      far. To provide a maximally efficient myotomy in a patient with a short pouch,
      the surgeon needs to be aware of the stapler differences. Modifications of the
      staplers may decrease the depth of the residual pouch, but may carry an added
      liability. A minimum residual pouch can be achieved with a combination of stapler
      and suture techniques, but is more technically demanding than the original ESED
      description.

PMID- 15966520
TI  - Fiberoptic endoscopic-assisted diverticulotomy: a novel technique for the
      management of Zenker's diverticulum.
AB  - Endoscopic diverticulotomy is rapidly becoming the procedure of choice for
      treatment of Zenker's diverticulum. The endoscopic approach has resulted in
      significant decreases in patient morbidity, time to resumption of oral intake,
      and overall cost as compared with open treatment. However, a small but
      significant patient population is unable to accommodate the rigid laryngoscope
      and therefore requires open treatment. We present a novel technique, flexible
      fiberoptic endoscopic-assisted diverticulotomy, for the management of patients
      who are unable to undergo rigid endoscopy.

PMID- 15966521
TI  - Effect of deficits in laryngeal sensation on laryngeal muscle biochemistry.
AB  - Swallowing deficits in elderly people are significant clinical problems and may
      be associated with impaired pharyngolaryngeal sensation. However, the extent to
      which sensory innervation affects the motor system is unclear. Our purpose was to
      examine differences in biochemical properties of laryngeal muscles following
      sensory nerve ablation. We used sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis to evaluate laryngeal muscles of young and old Fischer 344/Brown
      Norway rats, and rats that underwent sensory ablation via bilateral section of
      the superior laryngeal nerve, internal branch (SLNi), or mixed sensory-motor
      nerve ablation via left-sided recurrent laryngeal nerve (RLN) section. In lateral
      thyroarytenoid muscle, a reduction was found in the proportion of the most
      rapidly contracting myosin heavy chain isoform (type 2B) with SLNi section, RLN
      section, and aging. Section of the SLNi did not alter the proportion of any
      myosin heavy chain isoform within the lateral cricoarytenoid or posterior
      cricoarytenoid muscles, but RLN section resulted in a reduction in the proportion
      of type 2B. Accordingly, alteration in biochemical properties of the lateral
      thyroarytenoid muscle alone was demonstrated following sensory ablation. We
      conclude that sensory changes may affect properties of laryngeal muscles, and may
      thus have an impact on motor control during critical functions, such as airway
      protection during swallowing.

PMID- 15966522
TI  - Acute external laryngeal trauma: experience with 112 patients.
AB  - The purpose of this report is to promote early recognition, expeditious
      evaluation, and judicious management of acute external laryngeal trauma. A
      retrospective chart review was performed of 112 cases that were managed at a
      Medical College of Georgia tertiary care hospital by the senior author (E.S.P.).
      Patients were classified by the time of their presentation, the severity of their
      injury, and the treatment protocol followed. The clinical outcomes of airway,
      voice quality, and deglutition were retrospectively reviewed. For voice outcomes,
      in the delayed treatment group, only 27.7% of patients had a good result, as
      compared to a 78.3% good result in the early treatment group. Similar differences
      were demonstrated regarding the airway. In the delayed treatment group, only
      73.3% had good airway function, as compared to 93.3% who had good airway function
      in the early treatment group. Ninety-nine percent of all patients had a good
      result for deglutition. We conclude that expeditious diagnosis and intervention
      reduce the incidence of suboptimal clinical outcomes, and with timely and
      appropriate application of diagnostic and management protocols, the majority of
      patients will be successfully decannulated (97%) with functional speech (100%)
      and normal deglutition (99%).

PMID- 15966523
TI  - Laryngeal thrush.
AB  - Superficial fungal infection of the mucous membranes (thrush) isolated to the
      larynx is neither widely reported nor well recognized clinically. Therefore, it
      is often associated with ineffective treatment and delay in diagnosis, and
      sometimes associated with unneeded surgical intervention. Eight cases of thrush
      isolated to the larynx, with no oral or oropharyngeal manifestations, are
      presented. Four of these were isolated to the vocal folds alone. All patients
      were adults, and 4 were smokers. Hoarseness was always present. Pain was present
      inconsistently, and there was no dysphagia or odynophagia, in contrast to other
      forms of upper aerodigestive tract candidiasis. On average, diagnosis was not
      made until 6 months after the onset of symptoms. Possible causative factors
      included use of systemic steroids (3 cases), broad-spectrum antibiotics (1 case),
      or inhaled steroids (5 cases); diabetes (2 cases); and neutropenia (1 case). In 3
      cases, all with thrush isolated to the vocal folds, inhaled steroids were the
      only causative factor identifiable--a feature reported only twice previously.
      Three patients underwent surgical procedures that might have been avoided had an
      accurate diagnosis been made. All patients responded readily to oral fluconazole
      and removal of predisposing factors where possible. The signs, symptoms,
      predisposing factors, and treatment are compared to those of 14 cases reported in
      the literature over 35 years.

PMID- 15966524
TI  - Complete spontaneous regression of Merkel cell carcinoma.
AB  - Merkel cell carcinoma (MCC) is a very aggressive primary cutaneous neoplasm most
      often occurring on the head and neck of the elderly. Spontaneous regression of
      MCC was first described in 1986. A 79-year-old woman with MCC on the right cheek
      underwent spontaneous regression of the malignancy, documented by photographic
      follow-up, computed tomography, and histologic studies. A review of the
      literature is presented. Complete clinical and histologic regression of MCC was
      observed in the present case. Although the literature documents 11 similar cases,
      only 6 can be regarded as complete spontaneous regressions following exclusive
      performance of a biopsy (primary complete spontaneous regression). Primary
      complete spontaneous regression of MCC is infrequent, and most case reports
      describe this phenomenon in women with MCC on the cheek. The reasons underlying
      regression are unknown.

PMID- 15966525
TI  - Effect of cochlear implantation on residual spiral ganglion cell count as
      determined by comparison with the contralateral nonimplanted inner ear in humans.
AB  - It is generally assumed that at least a minimal number of spiral ganglion cells
      is essential for successful speech perception with a cochlear implant. Although
      the insertion of a multichannel cochlear implant frequently results in loss of
      residual hearing in the implanted ear, this outcome does not imply that
      significant damage to residual populations of spiral ganglion cells has occurred.
      The purpose of the current study was to compare spiral ganglion cell counts in
      implanted and nonimplanted cochleas in 11 patients for whom both temporal bones
      were available and in whom a multichannel cochlear implant had been placed
      unilaterally. The temporal bones were processed for light microscopy by standard
      techniques. The cochleas were reconstructed by 2-dimensional methods. Spiral
      ganglion cell counts of the implanted and nonimplanted sides were compared by a
      paired t-test (2-tailed). The mean spiral ganglion cell counts for implanted and
      nonimplanted ears were not statistically different in the most basal three
      segments of the cochlea. However, the mean spiral ganglion cell count in segment
      4 (apical segment) and the mean total spiral ganglion cell count were lower in
      the implanted cochleas than in the nonimplanted cochleas (p < .01). The results
      of this study suggest a modest decrease in the total spiral ganglion cell count
      in the implanted ears as compared to the nonimplanted ears, principally in the
      apical segment. Possible interpretations of this finding are discussed.

PMID- 15966526
TI  - Tissue-specific immunoglobulin E in human nasal polyps.
AB  - Allergy is generally believed to be an underlying cause of nasal polyps. The
      objective of this study was to define allergic nasal polyps. We investigated
      specific immunoglobulin E (sIgE) in polyp tissue. Thirty pieces of polyp tissue
      were taken from patients with positive allergic symptoms, and 30 from patients
      without allergic symptoms. Nasal polyp tissue homogenate and serum from these
      patients were prepared for detecting sIgE by a CAP method. For patients with
      allergic symptoms and/or positive serum CAP test results, the rates of positive
      tissue CAP tests were low: 36.7% and 35.7%, respectively. However, nearly all of
      the tissue CAP-positive subjects had allergic symptoms and positive serum CAP
      tests. We conclude that the local tissue sIgE profile reflects more specifically
      the allergic status of patients with nasal polyps than does the systemic serum
      test or the presentation of allergic symptoms. Thus, polyp tissue CAP tests might
      be performed in patients with positive allergic symptoms and positive serum CAP
      tests to define an allergy-induced polyp precisely. Then, specific antiallergic
      treatment could be administered to prevent polyp recurrence.

PMID- 15966527
TI  - Length of the human vocal folds: proposal of mathematical equations as a function
      of gender and body height.
AB  - To obtain a mathematical equation that could estimate the length of the
      intermembranous part of the vocal fold as a function of body height and gender,
      we removed the larynges from 39 cadavers (22 men and 17 women) after recording
      the subject's height, age, and cause of death. The dimensions of the vocal folds
      were determined with a digital pachymeter. The following equations were obtained:
      y = 0.18x - 15.8 for men and y = 0.24x - 28.1 for women, where y is the length of
      the intermembranous part of the vocal folds in millimeters and x is the height of
      the individual in centimeters. We conclude that it is possible to estimate the
      normal expected length of the intermembranous portion of the male and female
      vocal folds on the basis of body height.

PMID- 15966528
TI  - Rat model of platelet-activating factor-induced rhinosinusitis.
AB  - Platelet-activating factor (PAF) is known to be a potent inflammatory mediator,
      especially in allergic inflammation. However, the exact role of PAF in the
      pathogenesis of rhinosinusitis has not been clearly established. To understand
      the role of PAF in the pathogenesis of rhinosinusitis, it is necessary to develop
      an animal model of PAF-induced rhinosinusitis. The aim of this study was to
      develop a rat model of rhinosinusitis induced by intranasally applied PAF. Fifty
      microliters of 16 microg/mL PAF was applied intranasally through each naris in 4
      week-old Sprague-Dawley rats, and the same amount of vehicle was applied in
      control rats. At 1, 3, or 5 days, the animals were painlessly sacrificed, and the
      nasal cavity and sinuses were prepared for histologic investigation. The
      histologic sections were examined in a blind manner for the appearance of
      neutrophil clusters in the sinonasal air space, and the numbers of eosinophils,
      areas of epithelial loss, goblet cells, and inducible nitric oxide synthase
      (iNOS)-positive inflammatory cells in the mucosa. Neutrophil clusters were
      observed in the air space, and the number of eosinophils, areas of epithelial
      loss, goblet cells, and iNOS-positive inflammatory cells in the mucosa were
      increased significantly in the PAF-applied rats. The amount of inflammation
      varied according to the time interval, showing a peak at day 3. We conclude that
      intranasally applied PAF induces rhinosinusitis in rats. The histologic evidence
      of rhinosinusitis revealed the appearance of neutrophil clusters in the sinonasal
      air space, infiltration of eosinophils and iNOS-positive inflammatory cells in
      the mucosa, areas of epithelial loss, and goblet cell hyperplasia in the
      epithelium. This rat model of PAF-induced rhinosinusitis may be applied for
      better understanding of the role of PAF in the pathogenesis of rhinosinusitis.

PMID- 15966529
TI  - Effect of isoproterenol on the regulation of rabbit airway ciliary beat frequency
      measured with high-speed digital and fluorescence microscopy.
AB  - To investigate how isoproterenol, a beta-adrenergic agonist, regulates airway
      ciliary beat frequency (CBF), we simultaneously quantified changes in rabbit
      airway CBF and intracellular calcium concentration ([Ca2+]i) in response to
      isoproterenol (100 micromol/L) by using high-speed (240 frames per second) and
      fluorescence microscopy. At approximately 30 degrees C, isoproterenol induced a
      change in CBF that could be separated into two parts. First, isoproterenol
      induced a moderate increase in the basal CBF that was calcium-independent. This
      response was unaffected by buffering the [Ca2+]i with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrapotassium salt (BAPTA).
      Second, isoproterenol induced a transient increase in CBF that was superimposed
      on the increased basal CBF and correlated with a simultaneous transient increase
      in [Ca2+]i. This transient increase in CBF was abolished by BAPTA. We conclude
      that isoproterenol initially increases CBF through a calcium-independent
      mechanism, probably via protein kinase A, and subsequently through a calcium
      dependent mechanism mediated by an increase in [Ca2+]i.

PMID- 15966530
TI  - Fixation of soft tissue surrounded by bone with microwave irradiation: electron
      microscopic observation of guinea pig inner ear.
AB  - When electron microscopy is performed on organs such as the inner ear that cannot
      be removed immediately after decapitation of animals, it is necessary to fix the
      target organ or tissue by systemic or regional perfusion fixation. However, such
      methods of fixation can increase vascular pressure or perilymphatic pressure,
      making it difficult to perform precise morphological observation of the vascular
      endothelial cells and membranous labyrinth. We recently attempted fixation of the
      cochlea by microwave irradiation. Guinea pigs were decapitated. The bullas were
      then removed from each animal and fixed in a mixture of 2% paraformaldehyde and
      0.5% glutaraldehyde. Microwave (300 W) irradiation was then applied to the
      specimen for 1 minute. The fixative was immediately replaced with new fixative (4
      degrees C). This sequence of manipulations was repeated 10 times, for a
      cumulative microwave irradiation time of 10 minutes. During the microwave
      irradiation period, the fixative temperature was kept at about 30 degrees C.
      After the last round of irradiation, the specimens were kept immersed in the
      fixative for 1 hour. After a small slit was created in the bone on the lateral
      wall of the cochlea, the specimens were post-fixed in osmic acid and embedded in
      Epon 812. Each specimen was cut into halves along the plane containing the
      modiolus of the cochlea. After the bone on the lateral wall of the cochlea was
      cut off under a stereoscopic microscope, ultrathin sections were prepared for
      observation under a transmission electron microscope. With this technique, the
      stria vascularis and the organ of Corti were fixed to a degree comparable to or
      better than that achieved with the conventional method of fixation. Fixation with
      microwave irradiation is relatively simple and can solve the problems associated
      with perfusion fixation, and thus provides an excellent means of fixation. This
      technique appears to be particularly promising for fixation for soft tissue
      surrounded by bone.

PMID- 15966531
TI  - Larynx and cervical trachea in humidification and heating of inhaled gases.
AB  - To evaluate the participation of the larynx and cervical trachea in conditioning
      inspired gases, we randomly allocated 16 mixed-breed dogs to two groups: group TT
      (tracheal tube; n = 8) and group LMA (laryngeal mask airway; n = 8). The dogs
      were anesthetized with pentobarbital sodium and mechanically ventilated for 3
      hours. The parameters studied were temperature and absolute humidities of
      ambient, inhaled, and tracheal air. There was a small increase in tracheal air
      temperature compared to inhaled air temperature, but no significant difference
      between groups. The absolute humidity of tracheal air was greater in group LMA
      than in group TT (23 mg H2O * L(-1) and 14 mg H2O * L(-1), respectively; p <
      .0001). The difference in absolute humidity between the tracheal air and the
      inhaled air was higher in group LMA at all times (p < .0001). We conclude that
      the larynx and cervical trachea of the dog participate in humidification and
      heating of inhaled air by means of air contact with mucosa in this airway
      segment.

PMID- 15966532
TI  - Retroesophageal thyrothymic thyroid rest.

PMID- 15966533
TI  - Building better boards in the new era of accountability.
AB  - Healthcare boards are entering a new era of heightened accountability, scrutiny,
      and reform. Sarbanes-Oxley legislation, Internal Revenue Service scrutiny,
      pressure from creditors and bond insurers, activist state attorneys general,
      media attention, and other forces have sharply increased awareness of the
      importance of governance and have also raised the bar on what is required of
      boards and what is considered best-practice governance performance. Yet good
      governance cannot be legislated. The structure, composition, and specific
      required functions of boards can be legislated or mandated, but the effective
      function of boards cannot. At the same time that governance faces this new era of
      accountability, it is also being bombarded with the legions of monumental
      challenges in the tumultuous healthcare field. Chief executive officers and their
      boards must be willing to recognize the challenges and risks to the field of
      governance in general and to their boards in particular. Furthermore, they must
      be willing to implement new strategies and approaches for successful governance,
      including becoming compliant with Sarbanes-Oxley requirements; conducting a
      comprehensive audit of the structure, function, composition, and culture of the
      board; and seeking board members from outside the community, among many others.

PMID- 15966534
TI  - Priority issues for hospital boards.
AB  - Governing a hospital or healthcare system is a difficult and demanding job. If
      done properly, the organization can operate well. If the board is inept or
      incompetent, the organization will suffer. In this article I discuss those
      functions of board governance that I think are among the most important, along
      with some recommendations for implementing them.

PMID- 15966535
TI  - Governance: critical issues for hospital CEO and boards.

PMID- 15966536
TI  - The changing face of healthcare boards.

PMID- 15966537
TI  - Getting a grip on governance.

PMID- 15966538
TI  - Is the research sound?

PMID- 15966539
TI  - Current concepts in the recognition and treatment of superior labral (SLAP)
      lesions.
AB  - Pathology of the superior aspect of the glenoid labrum (SLAP lesion) poses a
      significant challenge to the rehabilitation specialist due to the complex nature
      and wide variety of etiological factors associated with these lesions. A thorough
      clinical evaluation and proper identification of the extent of labral injury is
      important to determine the most appropriate nonoperative and/or surgical
      management. Postoperative rehabilitation is based on the specific surgical
      procedure as well as the extent, location, and mechanism of labral pathology and
      associated lesions. Emphasis is placed on protecting the healing labrum, while
      gradually restoring range of motion, strength, and dynamic stability of the
      glenohumeral joint. The purpose of this paper is to provide an overview of the
      anatomy and pathomechanics of SLAP lesions and review specific clinical
      examination techniques used to identify these lesions, including 3 newly
      described tests. Furthermore, a review of the current surgical management and
      postoperative rehabilitation guidelines is provided.

PMID- 15966540
TI  - Gender comparison of hip muscle activity during single-leg landing.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To determine whether
      gender differences in electromyographic (EMG) activity of hip-stabilizing muscles
      are present during single-leg landing. BACKGROUND: Numerous factors may explain
      the greater rate of anterior cruciate ligament (ACL) injuries in female athletes.
      However, gender differences in hip muscle activity during dynamic events have not
      been well characterized. METHODS AND MEASURES: Twenty-two Division I collegiate
      athletes (13 female, 9 male) performed drop landings from 30.5- and 45.8-cm
      heights. Surface EMG was used to examine relative muscle activity from 200
      milliseconds prior to initial contact to 250 milliseconds postcontact. Peak and
      mean values for each muscle (gluteus maximus, gluteus medius, rectus femoris) in
      each time epoch were analyzed using 2 x 2 (group by height) analyses of variance
      (ANOVAs) to determine significance. RESULTS: Females demonstrated lower gluteus
      maximus peak (mean +/- SD, 69.5 +/- 30.2 versus 98.0 +/- 33.4 percent maximum
      voluntary contraction [%MVIC]; P= .019) and mean (mean +/- SD, 37.5 +/- 15.6
      versus 53.9 +/- 18.0 %MVIC; P = .018) muscle activation during the postcontact
      phase of landing than males. Furthermore, females demonstrated greater peak
      rectus femoris activity during the precontact phase (mean +/- SD, 33.6 +/- 18.5
      versus 18.7 +/- 8.2 %MVIC; P = .029). A positive effect of drop height on
      relative activity of all muscles was observed during both phases (P<.05).
      CONCLUSIONS: Females utilize different muscular activation patterns compared to
      males (ie, decreased gluteus maximus and increased rectus femoris muscle
      activity) during landing maneuvers. Decreased hip muscle activity and increased
      quadriceps activity may be important contributors to the increased susceptibility
      of female athletes to noncontact ACL injuries.

PMID- 15966541
TI  - Screening for vertebrobasilar insufficiency in patients with neck pain: manual
      therapy decision-making in the presence of uncertainty.
AB  - Growing evidence supports the effectiveness of manual therapy interventions in
      patients with neck pain; however, considerable attention has also been afforded
      to the potential risks such as vertebrobasilar insufficiency (VBI). Despite the
      existence of guidelines advocating specific screening procedures, research does
      not support the ability to accurately identify patients at risk. The logical
      question becomes, "How does one proceed in the absence of certainty?" Given the
      lack of clear direction for decision making in the peer-reviewed literature, this
      commentary discusses the uncertainties that exist regarding the ability to
      identify patients at risk for VBI. The authors hope that this commentary adds
      additional perspective on manual therapy decision-making strategies in the
      presence of uncertainty.

PMID- 15966542
TI  - Associations between turnout and lower extremity injuries in classical ballet
      dancers.
AB  - STUDY DESIGN: Descriptive correlational study. OBJECTIVES: To determine
      relationships between aspects of turnout and injury history in preprofessional
      classical ballet dancers, and to determine the clinical utility of various
      methods used to assess turnout. BACKGROUND: In Australia 50% of professional
      dancers currently have persistent or recurrent injuries, with 36% of these
      injuries commencing before 18 years of age (preprofessional level). Overuse or
      nontraumatic dance injuries are often attributed to faults in technique, with
      poor turnout and inappropriate compensatory strategies consistently cited as the
      main cause. METHODS AND MEASURES: Twenty-nine dancers (24 female), aged 15 to 22
      years, were recruited from a preprofessional classical ballet program.
      Measurements were taken of passive and active hip external rotation (ER) range of
      motion (ROM) in supine, and functional turnout angles in standing. Three turnout
      variables were derived: active ER lag, compensated turnout, and static-dynamic
      turnout difference. Injury history over the previous 2 years was ascertained by
      interview. Pearson product moment and Spearman rank correlation coefficients were
      used to determine associations between turnout variables and injury history.
      RESULTS: All dancers reported a history of injury, with 93.1% reporting a history
      of nontraumatic injuries and 41.4% reporting a history of traumatic injuries.
      Number and severity of nontraumatic injuries were associated with reduced
      functional turnout (r or rho>0.38; P<.04), but not with hip ER ROM. Number and
      severity of traumatic injuries were not associated with turnout. No correlation
      was found between hip ER ROM and functional turnout. CONCLUSIONS: Functional
      measures of turnout are more relevant than hip ER ROM to prevalence of
      nontraumatic dance injuries. Control of turnout in classical ballet dancers
      should be assessed dynamically and in functional positions.

PMID- 15966543
TI  - Differential diagnosis of spondylolysis in a patient with chronic low back pain.
AB  - STUDY DESIGN: Resident's case problem. BACKGROUND: A 26-year-old male sought
      physical therapy services via direct access secondary to a flare-up of a chronic
      low back pain condition. The patient complained of recent onset of lumbosacral
      joint pain, including (1) constant right-sided deep-bruise sensation, (2)
      intermittent right-sided sharp stabbing pain, and (3) constant bilateral aching.
      The patient's past medical history included a hyperextension low back injury
      while playing football at age 17. Physical examination revealed (1) deep pain
      with palpation over the right lumbosacral joint region, (2) sharp right
      lumbosacral joint pain with 1 repetition of active trunk backward bending, and
      (3) a marked increase in pain and joint hypomobility with right unilateral joint
      assessment at the L4 and L5 spinal levels. DIAGNOSIS: The examining therapist
      referred the patient for radiographic evaluation due to strong suspicions of a
      pars interarticularis bony defect. Lumbar plain films, oblique views, revealed an
      L5 bilateral pars defect, leading to a diagnosis of a longstanding bilateral L5
      spondylolysis. DISCUSSION: Patients with low back pain often seek physical
      therapy services. Identification of pathology requiring examination by other
      health care providers, leading to patient referral to other health care
      practitioners, is a potential important outcome of the therapist's examination.
      This resident's case problem illustrates the importance of a systematic
      examination scheme, including a thorough medical screening component that led to
      a patient referral for radiographic evaluation. The resultant diagnosis, although
      not representing serious pathology, did impact the therapist's patient plan of
      care.

PMID- 15966544
TI  - Second international ankle symposium summary statement.

PMID- 15966545
TI  - The complex etiology of lateral ankle instability.

PMID- 15966546
TI  - Sensory deficits with ankle injuries.

PMID- 15966547
TI  - Efficacy of control during sudden ankle inversion.

PMID- 15966548
TI  - Rehabilitation of the unstable ankle.

PMID- 15966549
TI  - Foot structure, mechanics, and injury risk.

PMID- 15966550
TI  - Premenarcheal Mexican girls' and their teachers' perceptions of preparation
      students receive about menstruation at school.
AB  - This survey explored how fifth-grade Mexican premenarcheal girls (N = 80) and
      their teachers (N = 16) view the preparation students receive about menstruation
      at school. The most discussed topics in class included hygiene and body
      functions. The main discrepancies between girls and teachers were as follows: (a)
      more teachers than girls reported that they discussed the emotional aspects of
      menses, (b) teachers indicated that their pupils were better prepared than the
      students themselves believed. (c) more teachers reported that the girls acted
      ashamed during the classes, and (d) more girls perceived that boys behaved in a
      mocking manner, whereas more teachers thought that the boys acted nervous. In
      conclusion, teaching about menstruation is problematic, but these findings
      provide information for teachers to meet the needs of girls more efficiently.

PMID- 15966551
TI  - A review of 21 curricula for abstinence-only-until-marriage programs.
AB  - The authors reviewed the content, methods, and overall quality of 21 curricula
      used in abstinence-only-until-marriage programs. Only materials designed for use
      in middle school grades (fifth to eighth) or with middle school-aged audiences (9
      13 years of age), which presented the abstinence message in at least 40% of their
      content, were included. A rating instrument adapted from 2 sets of education
      guidelines structured the assessment of each curriculum. Four experienced
      teachers rated each curriculum. Curricula exhibited considerable variability in
      overall quality ratings. While on average, materials scored a 3.33 on a 1-to-5
      scale (1 = Unacceptable; 5 = Excellent), 12 curricula received summative scores
      above the average, with 4 scoring 4.0 or higher. Eight curricula, however,
      received a below-average rating. While abstinence materials vary considerably in
      terms of overall quality, the values and world views underlying this sample of
      curricula were clear and consistent: those who develop abstinence education
      curricula value nonsexual antecedents of sexual behavior such as skills (goal
      setting, decision making, and assertiveness), ideals (fidelity, friendships), and
      psychological factors such as self-esteem.

PMID- 15966552
TI  - Teacher beliefs, professional preparation, and practices regarding exceptional
      students and sexuality education.
AB  - Sexuality education, part of the comprehensive school health education component
      of a Coordinated School Health Program, interests many health educators as well
      as special education teachers. In this study, Florida special educators reported
      their beliefs about teaching sexuality education to educable mentally disabled
      students, the range of sexuality topics they teach, and their professional
      preparation in sexuality education. Respondents (n = 494) completed a mailed
      instrument that included the 36 sexuality content areas identified by the
      Sexuality Information and Education Council of the United States. Respondents
      believed strongly that many of the sexuality topics and content areas should be
      taught to educable mentally disabled students. However, most reported delivering
      only a modest amount of sexuality education, and they rated their professional
      preparation as inadequate. Regression analyses documented that respondents'
      beliefs predicted the topics they actually taught within 5 of the 6 key concepts.
      This study supports collaboration between health educators and special education
      teachers to adapt existing sexuality curricula for students with special needs,
      improve professional preparation of special education teachers to teach sexuality
      education, and to more effectively implement comprehensive school health
      education through the Coordinated School Health Program model to special
      education students.

PMID- 15966553
TI  - Elementary school teachers' involvement in firearm safety education.
AB  - This national study assessed elementary school teachers' (n = 352) firearm safety
      education activities and perceptions using a 3-wave mailing survey. One percent
      of the teachers reported receiving undergraduate training regarding firearm
      safety. Yet, 12% claimed to be well prepared or very well prepared to teach
      firearm safety. Most teachers had high perceived self-efficacy regarding teaching
      firearm safety and perceived firearm safety education as important. Ten percent
      were currently teaching firearm safety. Teachers perceived 3 main barriers to
      teaching firearm safety: not enough expertise (66%), not sure what topics should
      be taught (58%), and not enough time to include firearm safety in the curriculum
      (54%). About one third (35%) desired further information regarding teaching
      firearm safety.

PMID- 15966554
TI  - Promoting school health--an expanded paradigm.

PMID- 15966555
TI  - Exploring male-female communication: three lessons on gender.

PMID- 15966556
TI  - Hypertension in type 2 diabetes--targeting angiotensin.
AB  - Cardiovascular disease accounts for around 60% of deaths in people with type 2
      diabetes mellitus, and diabetes is the leading cause of renal dysfunction and
      premature death in the UK. A key factor in these outcomes is that many people
      with type 2 diabetes also have raised blood pressure, which increases the
      likelihood of vascular complications. Lowering elevated blood pressure, using one
      or more antihypertensive drugs, reduces illness and mortality rates in such
      people. National guidelines advocate the use of angiotensin-converting enzyme
      (ACE) inhibitors or angiotensin-II receptor antagonists in selected patients with
      type 2 diabetes. Here we review whether such treatment offers advantages over
      other antihypertensive drugs.

PMID- 15966557
TI  - Hypnotherapy for functional gastrointestinal disorders.
AB  - About 20% of people in the UK have functional gastrointestinal disorders such as
      irritable bowel syndrome and functional dyspepsia. These conditions account for
      about 4% of GP consultations and 50% of gastroenterologists' workload. Forsome,
      the symptoms affect quality of life and ability to work. Drug treatment aimed at
      relieving symptoms is often ineffective. Other options include psychological
      treatments such as cognitive behavioural therapy, brief psychotherapy and gut
      directed hypnotherapy. Here we discuss whether hypnotherapy has a role in the
      treatment of patients with irritable bowel syndrome or functional dyspepsia.

PMID- 15966558
TI  - Polycystic ovary syndrome in adolescents: pathophysiology and treatment
      implications.
AB  - Polycystic ovary syndrome is a heterogeneous clinical syndrome, which has been
      defined as the association of hyperandrogenism with chronic anovulation in women
      without specific adrenal and pituitary gland disease. A family history of
      polycystic ovary syndrome may be present in a subset of patients; however, the
      genetic basis of the syndrome remains unclear. Most often, the age of onset is
      perimenarchal and it is characterized by the appearance of menstrual
      disturbances, hirsutism, acne, and more rarely, a male pattern of alopecia. In
      some cases, premature adrenarche may present as a precursor to the development of
      the syndrome. Polycystic ovary syndrome is also associated with metabolic
      disturbances, such as obesity and insulin resistance with hyperinsulinemia, for
      which the pathophysiological role in the development of the syndrome has been
      recognized. The therapeutic approaches to polycystic ovary syndrome include
      lifestyle modifications, dietary-induced weight loss, insulin-sensitizing agents,
      antiandrogens, and oral contraceptives. These treatments may improve the clinical
      manifestations of excess androgen production and normalize menses in many
      adolescents and young women with polycystic ovary syndrome. Early recognition of
      the syndrome and thus, early treatment, may prevent and possibly ameliorate all
      the symptoms and the potential later development of metabolic and cardiovascular
      complications.

PMID- 15966559
TI  - Pathogenesis and management of diabetic dyslipidemia.
AB  - Patients with diabetes mellitus have a 2- to 4-fold increased risk of
      atherosclerotic cardiovascular, peripheral vascular, and cerebrovascular disease,
      which are the leading causes of morbidity and mortality in this population.
      Several epidemiological studies have shown an association between diabetic
      dyslipidemia, which is characterized by hypertriglyceridemia, low levels of high
      density lipoprotein-cholesterol, postprandial lipemia and small, dense low
      density lipoprotein-cholesterol (LDL-C) particles, and the occurrence of
      cardiovascular disease. Other studies have established the beneficial effects of
      lipid lowering on the reduction of major coronary events in diabetic patients.
      The recent National Cholesterol Education Program (NCEP) Adult Treatment Panel
      III (ATP III) guidelines emphasize diabetes as a coronary heart disease risk
      equivalent. The NCEP ATP III states that elevated LDL-C is a major risk factor
      for coronary heart disease, and the primary goal of risk-reduction therapy is the
      reduction of LDL-C levels to 100 mg/dL. This article defines and describes
      diabetic dyslipidemia and its etiology and pathogenesis, as well as reviewing
      guidelines and recommendations for treatment of this disorder. Treatment of
      diabetic dyslipidemia includes 1) lifestyle modifications: physical activity and
      a diet low in saturated fats and cholesterol and high in complex carbohydrates
      and fiber; and 2) pharmacological treatment with (i) oral antihyperglycemic
      agents: metformin and thiazolidinediones; (ii) weight reduction drugs: orlistat
      and sibutramine and; (iii) lipid-lowering drugs: HMG-CoA reductase inhibitors,
      fibric acid derivatives, nicotinic acid, and bile acid sequestrants.

PMID- 15966560
TI  - Advances in female hormonal contraception: current alternatives to oral regimens.
AB  - Despite the wide variety of reversible contraceptives, unintended pregnancy rates
      in developed nations are still considered markedly elevated by most
      epidemiologists and clinicians. Indeed, the US has one of the highest unintended
      pregnancy rates among the industrialized nations of the world. Although many
      factors appear to influence this problem, what may play an important role in this
      apparent paradox is the process by which a woman obtains contraception. Although
      most nonbarrier methods have similar efficacy, the ability to use that method
      consistently and correctly will determine whether it provides maximal
      contraception. Oral contraceptives are the most popular method in the US;
      accordingly, the process by which US women obtain their contraception may not
      take into account the desire of many women to use nondaily methods. The recent
      introduction of nondaily methods in the US and elsewhere has provided more choice
      so that a successful contraceptive decision can be made in the first instance
      rather than after an adverse clinical outcome or unintended pregnancy with a
      method not as well suited to that woman's lifestyle. These new methods are not
      characterized by improved safety or efficacy; rather, they have novel components
      or delivery systems that may provide important options to women who may not be
      able to or willing to use existing methods of contraception. The transdermal
      patch, vaginal ring, and monthly injectable are combination estrogen/progestogen
      methods characterized by novel delivery systems and compliance regimens. The
      single rod implant is a facile and well accepted method that has not yet been
      approved for use in the US but has been an increasingly popular choice elsewhere.
      The levonorgestrel intrauterine system has been used in Europe for over 10 years
      and has recently been introduced in the US. This intrauterine contraceptive
      provides high efficacy and reliability, and may have considerable
      noncontraceptive benefit with regard to the nonsurgical treatment of uterine
      bleeding problems and endometrial protection for menopausal hormone therapy. The
      increasing popularity of these methods can be considered a testament to the
      desire of women to consider nondaily contraceptives as first-line, mainstream
      options. It is hoped that increasing use of these methods will lead to a
      considerable decrease in the rate of unintended pregnancy.

PMID- 15966561
TI  - Managing and predicting low response to standard in vitro fertilization therapy:
      a review of the options.
AB  - Low responders remain a difficult group of patients to manage in an in vitro
      fertilization (IVF) program. Such patients have low peak estradiol concentrations
      (<500 ng/L) and few dominant follicles on the day of human chorionic gonadotropin
      administration (<5 to <2), and therefore have few retrieved mature oocytes (< or
      = 4 to < or = 6) with resultant lower pregnancy rates when stimulated with
      standard IVF therapy (daily gonadotropin dose 150-300IU [2-4 ampoules]). It is
      difficult to compare the various strategies that have been utilized to manage low
      responders because the definition of a low responder varies widely. Also, very
      few large prospective randomized trials have compared different protocols. Two
      stimulation protocols involving varying doses of leuprorelin and high doses of
      gonadotropins appear to be the most promising. The early gonadotropin-releasing
      hormone (GnRH) agonist cessation protocol involves routine pituitary
      desensitization with luteal phase start of leuprorelin 0.5 mg for 10-14 days.
      With the onset of gonadotropin treatment, there is cessation of leuprorelin. The
      'microdose flare' protocol utilizes oral contraceptive priming followed by
      diluted doses of leuprorelin 50 microg given twice daily. Two days later,
      stimulation is started by adding high doses of gonadotropins. The microdoses of
      leuprorelin and the high doses of gonadotropins are then continued until the day
      of chorionic gonadotropin administration. Patients who do not respond to these
      protocols or those with severely diminished ovarian reserve are candidates for
      donor oocytes. The role of GnRH antagonists and the in vitro maturation of
      oocytes are potentially exciting strategies that are still being investigated.
      Ultrasound measurements of ovarian volume, baseline antral follicle counts, and
      Doppler measurement of ovarian stromal blood flow now make it possible to predict
      low response to IVF therapy. Low response can be expected if the smaller ovary
      has a volume <3 cm3, or the mean ovarian diameter in the two longest planes is
      <20 mm. Antral follicle counts of < or = 3 in each ovary are also associated with
      low response. Data on ovarian stromal blood flow are still unclear, but an
      ovarian peak systolic velocity of <10 cm/sec is associated with low response. If
      low response is anticipated based on baseline ultrasound scan, a switch to one of
      the two effective stimulation protocols should be initiated. This would reduce
      cancellation rates and improve pregnancy rates in the first cycle of IVF.

PMID- 15966562
TI  - Current management strategies for hypercalcemia.
AB  - The two most common causes of hypercalcemia are primary hyperparathyroidism and
      neoplastic disease. Parathyroidectomy is the only curative intervention for the
      former condition. In the rare cases of patients with primary hyperparathyroidism
      who present with clinical symptoms due to their hypercalcemia, pharmacological
      treatment may be required. Fluid repletion and intravenous (IV) administration of
      bisphosphonates are recommended in the literature. Calcium receptor agonists
      (calcimimetic agents) are at the present time only available for use within
      clinical trials. Cancer patients usually present with symptoms of hypercalcemia.
      Rapid institution of antihypercalcemic treatment is essential in preventing life
      threatening deterioration. Fluid repletion and administration of bisphosphonates
      are the treatment mainstays in hypercalcemia of malignancy. Five bisphosphonates
      are currently licensed in Europe for treatment of tumor-associated hypercalcemia:
      etidronate, clodronate, pamidronate, ibandronate, and zoledronate. In the US,
      pamidronate and zoledronate are licensed for use in this indication.
      Bisphosphonates containing nitrogen atoms (e.g. pamidronate, ibandronate, and
      zoledronate) are more potent than those without (e.g. etidronate, clodronate, and
      tiludronate). In patients with malignant hypercalcemia, the efficacy of the
      individual bisphosphonate depends on dose administered and initial serum calcium
      concentration. At present, pamidronate has been studied in the greatest number of
      investigations and in the largest number of patients. In the literature, the
      efficacy of pamidronate in restoring normocalcemia ranges between 40% and 100%,
      depending on the dose used and baseline serum calcium concentration. More
      recently, one study reported that pamidronate was inferior to zoledronate. In
      this study, the duration of response was also longer in the two zoledronate
      groups (30 and 40 days) than in the pamidronate group (17 days). The most serious
      adverse events of bisphosphonates concern renal function. Increases in serum
      creatinine levels have been more frequently reported following treatment of tumor
      associated hypercalcemia with etidronate (8%) and clodronate (5%) than with the
      nitrogen-containing bisphosphonates pamidronate (2%) and ibandronate (1%). The
      frequency of increases in serum creatinine levels following treatment with
      zoledronate is difficult to estimate. Administration of the nitrogen-containing
      bisphosphonates has been associated with transient (usually mild) fever,
      lymphocytopenia, malaise, and myalgias. These events occur within 36 hours of the
      first dose and are self-limiting. Hypocalcemia occurs in up to 50% of patients
      treated with bisphosphonates for hypercalcemia of malignancy, although
      symptomatic hypocalcemia is rare. The toxicity and low efficacy of plicamycin
      (mithramycin) mean that use of this agent should be restricted to patients with
      hypercalcemia of malignancy who fail to respond to IV bisphosphonates. Calcitonin
      is characterized by good tolerability but poor efficacy in normalizing the serum
      calcium level. However, a major advantage of calcitonin is the acute onset of the
      hypocalcemic effect, which contrasts with the delayed but more pronounced effect
      of bisphosphonates. Combination calcitonin and bisphosphonate treatment may
      therefore be of value when rapid reduction of serum calcium is warranted. Gallium
      nitrate may be a valuable treatment for hypercalcemia of malignancy. It is
      characterized by high efficacy and few adverse events apart from renal toxicity
      (10% of cases). However, data are very limited and further trials are necessary.

PMID- 15966563
TI  - Alcohol for the prevention of type 2 diabetes mellitus?
AB  - While diabetes mellitus is recognized clinically as a complication of alcohol
      dependence, in the last 15 years several large prospective studies have
      demonstrated a significant reduction in risk of incident type 2 diabetes in
      moderate drinkers. In this article, we review prospective studies on the
      association between alcohol consumption and incidence of diabetes. Few
      prospective studies have demonstrated an unequivocal positive association between
      alcohol use and incidence of diabetes. A number of large prospective studies have
      now demonstrated an inverse association: typically a 40% risk reduction after
      controlling for other major risk factors. Studies based on cohorts of health
      professionals have not demonstrated an increased risk of diabetes with heavier
      consumption, but these cohorts contain few heavy drinkers. Some cohorts drawn
      from the general population have shown a J- or U-shaped association between level
      of alcohol consumption and incidence of diabetes. Frequent moderate drinking has
      been reported to be associated with lower risk than infrequent drinking. There
      have been contradictory reports on the importance of the type of alcoholic
      beverage and whether the effect of alcohol differs according to the bodyweight of
      the drinker. We conclude that like many other chronic diseases, there is a
      delicate balance between the harmful and beneficial effects of alcohol on the
      incidence of diabetes. In moderate amounts, drinking is associated with a reduced
      risk of diabetes, whereas in higher amounts with an increased risk.

PMID- 15966564
TI  - Natural and synthetic growth hormone secretagogues: do they have therapeutic
      potential?
AB  - Ghrelin, a 28 amino acid-acylated peptide predominantly produced by the stomach,
      displays strong growth hormone (GH)-releasing activity. It is mediated by the
      hypothalamic-pituitary GH secretagogue (GHS) receptors, which are specific to a
      family of synthetic, orally active molecules known as GHSs. However, despite
      their potent and reproducible GH-releasing activity, the potential clinical use
      of GHSs as orally active growth-promoting agents or anabolic anti-aging drugs has
      not been confirmed. Ghrelin and GHSs also exert other actions mediated through
      central and peripheral receptors, including stimulation of adrenocorticotrophic
      hormone and prolactin secretion, influence on insulin secretion and glucose
      metabolism, orexigenic effects and modulatory activity on the neuroendocrine and
      metabolic response to starvation, influence on exocrine gastro-entero-pancreatic
      functions, cardiovascular effects and modulation of cell proliferation and
      apoptosis. The discovery of ghrelin and the characterization of these GH
      independent biological activities has widened the knowledge of some critical
      aspects of neuroendocrinology and suggests possible roles for GHSs and ghrelin in
      the treatment of pathophysiological conditions, including those unrelated to
      disorders of GH secretion.

PMID- 15966565
TI  - The role of somatropin therapy in children with Noonan syndrome.
AB  - Patients with Noonan syndrome, which is thought to have an incidence of 1 : 1,000
      to 1 : 2,500 live births, have variable hypogonadism together with features such
      as pulmonary valvular stenosis, dysmorphism, deafness, visual problems,
      cryptorchidism, clotting disorders, and short stature. Noonan syndrome is now
      known to be associated with mutations in the PTPN11 gene encoding the protein
      tyrosine phosphatase SHP-2 on chromosome 12 (12q24.1). This discovery will
      facilitate both knowledge of the true incidence and phenotypic diversity. There
      are poor genotype-phenotype correlations in Noonan syndrome, and the currently
      defined gene abnormalities only account for a minority of those identified on a
      clinical basis. Puberty in patients with Noonan syndrome generally occurs
      spontaneously but is typically delayed. Mean adult height is 162.5cm (men) and
      153cm (women), although standards are based on relatively small samples of
      largely cross-sectional data and are subject to ascertainment bias. Available
      evidence suggests that there may be disturbance of the growth hormone/insulin
      like growth factor axis in Noonan syndrome and that somatropin (growth hormone
      therapy) dose-dependently improves vertical growth in the short to medium-term.
      Final height data from a number of European studies will be available later in
      2003. Noonan syndrome patients with echocardiographic features of hypertrophic
      cardiomyopathy may be at particular risk from somatropin therapy because of its
      known effects on cardiac muscle mass; these patients have generally been excluded
      from trials of somatropin. Unbiased evidence for the efficacy and safety of
      somatropin therapy in Noonan syndrome will come from appropriately controlled
      studies of sufficiently large numbers of patients defined on such a basis and
      followed to final height. This is now possible but will require international
      cooperation. Nevertheless, the clinical relevance of somatropin therapy in Noonan
      syndrome and other short stature syndromes will be dependent on looking beyond
      improvement in final height (even if achievable) to psychological and quality of
      life outcomes.

PMID- 15966566
TI  - Pancreatic islet cell transplantation: progress in the clinical setting.
AB  - Pancreatic islet cell transplantation as a treatment for diabetes has hitherto
      been confined to small patient cohorts with limited success. This article
      summarizes the results of islet cell transplantation before and after the advent
      of the new 'Edmonton protocol' of immunosuppression and management of the donor
      pancreas. Adopting this regimen has achieved unprecedented success and renewed
      interest in this potential cure for diabetes. Central to recent improvements in
      the technique has been the transplantation of an adequate islet mass. Improved
      methods to procure, isolate, and purify islets for clinical use are now being
      adopted as a new 'gold standard'. The use of new immunosuppressive drugs has
      further improved clinical results. Corticosteroid sparing-based regimens, and
      agents such as humanized monoclonal antibodies, are likely to form the mainstay
      of immunosuppressive protocols with the aim of achieving donor-specific
      tolerance. Alternative sources of islet cells are also required to expand the
      technique in an era of reduced numbers of donor pancreata. Manipulation of stem
      cells and xenotransplantation may yet yield sufficient islets to overcome the
      problem of donor shortage. Islet cell transplantation now forms the basis of a
      prospective multicenter trial under the aegis of the Immune Tolerance Network.
      The results of this are awaited, but it appears that islet cell transplantation
      may yet emerge as an effective treatment option for some members of the diabetic
      population.

PMID- 15966568
TI  - Opinion and evidence for treatments in endocrine disorders.
AB  - New treatments and treatment protocols for endocrine disorders are evolving
      rapidly, and research and development activity in the endocrinology field is
      high. Optimal therapy remains contentious in some areas. To help you keep up-to
      date with the latest advances worldwide on all aspects of drug therapy and
      management of endocrine disorders, this section of the journal brings you
      information selected from the rapid drug news alerting service Inpharma Weekly.
      Each issue contains easy-to-read summaries of the most important research and
      development news, clinical studies, treatment guidelines, pharmacoeconomic and
      adverse drug reaction news, and expert opinion pieces published in the world's
      top endocrinology journals.

PMID- 15966567
TI  - Transdermal ethinylestradiol/norelgestromin: a review of its use in hormonal
      contraception.
AB  - Ethinylestradiol 20 microg/day plus norelgestromin 150 microg/day have been
      formulated into a transdermal patch for hormonal contraception. The predominant
      mechanism of action for transdermal ethinylestradiol/norelgestromin (Ortho Evra,
      Evra) is inhibition of ovulation by suppression of gonadotropins. It suppresses
      follicular development, induces changes to the endometrium that reduce the
      probability of implantation, and increases the viscosity of cervical mucus, which
      may prevent sperm penetration into the uterus. Two large randomized, nonblind
      efficacy studies demonstrated that transdermal ethinylestradiol/norelgestromin
      was as efficacious in preventing pregnancy as oral triphasic
      ethinylestradiol/levonorgestrel or oral ethinylestradiol/desogestrel. A large,
      noncomparative study also showed transdermal ethinylestradiol/norelgestromin to
      have good contraceptive efficacy. Moreover, in the two comparative trials, women
      using transdermal ethinylestradiol/norelgestromin had higher rates of perfect
      compliance than women using oral contraception. Age did not affect the rate of
      perfect compliance in women using the transdermal ethinylestradiol/norelgestromin
      patch, whereas the rate of compliance reduced with younger age in oral
      contraceptive users. Pooled results from three efficacy studies found that 1.8%
      of patches were replaced as a result of complete detachment and 2.9% because of
      partial detachment. Physical exercise, water immersion, and living in a humid
      climate did not affect patch adhesion. Transdermal
      ethinylestradiol/norelgestromin was generally well tolerated in clinical trials.
      The most common menstrual disturbances were breakthrough bleeding/spotting and
      dysmenorrhea. The incidence of discontinuation of treatment because of an adverse
      event was < or = 3.2%, with the most common reason being application-site
      reactions. CONCLUSIONS: Transdermal ethinylestradiol/norelgestromin offers a well
      tolerated, effective, reversible, and easy-to-use method of hormonal
      contraception with an increased likelihood of compliance relative to oral
      contraceptives.

PMID- 15966569
TI  - Effect of bis[curcumino]oxovanadium complex on non-diabetic and streptozotocin
      induced diabetic rats.
AB  - The effect of the vanadium complex bis[curcumino]oxovanadium (BCOV) on blood
      glucose level, serum lipid levels, blood pressure and vascular reactivity were
      studied in non-diabetic and streptozotocin-induced diabetic (STZ-diabetic) rats
      and compared to that of vanadyl sulfate. Blood glucose level, serum lipid levels,
      and blood pressure were significantly increased in STZ-diabetic rats. Vascular
      reactivity to various agonists such as noradrenaline and acetylcholine were
      significantly increased in STZ-diabetic rats. Blood glucose and serum lipid
      levels were restored to normal in STZ-diabetic animals treated with vanadyl
      sulfate at a concentration of 0.5 mmol/kg/day (p.o.). However, vanadyl sulfate at
      a concentration of 0.2 mmol/kg/day (p.o.) did not produce any significant change
      in blood glucose and lipid levels. There was no significant effect of vanadyl
      sulfate (0.2 or 0.5 mmol/kg/day) treatment on blood pressure and vascular
      reactivity in STZ-diabetic rats. Vanadyl sulfate significantly reduced the body
      weight of non-diabetic and STZ-diabetic rats. Moreover, it also caused severe
      diarrhea in both groups of animals. Treatment with BCOV (0.05, 0.1 and
      0.2mmol/kg/day, p.o.) significantly decreased blood glucose level and serum
      lipids in STZ-diabetic rats. Furthermore, administration of BCOV to STZ-diabetic
      rats restored the blood pressure and vascular reactivity to agonists to normal.
      There was no significant change in the body weight of BCOV treated non-diabetic
      and STZ-diabetic rats. Diarrhea was not observed in both BCOV treated groups. In
      conclusion, the present study shows that the vanadium complex BCOV has
      antidiabetic and hypolipedimic effects. In addition, it improves the
      cardiovascular complications associated with diabetes.

PMID- 15966570
TI  - Antineoplastic activity of new lanthanide (cerium, lanthanum and neodymium)
      complex compounds.
AB  - Cerium (III), lanthanum (III) and neodymium (III) complexes with 3,3'
      benzylidenebis[4-hydroxycoumarin] were synthesized in view of their application
      as cytotoxic agents. The complexes were characterized by different
      physicochemical methods: elemental analysis, mass spectrometry, 1H NMR, 13C NMR
      and IR spectroscopy. The spectra of the complexes were interpreted on the basis
      of comparison with the spectrum of the free ligand. The vibrational analysis
      showed that in the complexes the ligand coordinated to the metal ion through both
      deprotonated hydroxyl groups; however, participation of the carbonyl groups in
      the coordination to the metal ion was also suggested. The evaluation of the
      cytotoxic activity of the novel lanthanide complexes on HL-60 myeloid cells
      revealed that they are potent cytotoxic agents. The cerium complex was found to
      exhibit superior activity in comparison to the lanthanum and neodymium
      coordination compounds, the latter being the least active. Our data give us
      reason to conclude that the newly synthesized lanthanide complexes should be
      submitted to further more detailed pharmacological and toxicological evaluation.

PMID- 15966572
TI  - The relationship between trace elements and cardiac markers in acute coronary
      syndromes.
AB  - Previous studies have demonstrated increased serum copper and iron levels and
      decreased selenium and zinc levels in patients with myocardial infarction.
      Furthermore, the prognostic value of the levels of trace elements in myocardial
      infarction has been stressed. We examined serum levels of Cu, Fe, Zn and Se, as
      well as glutathione peroxidase (GPx), a selenoenzyme with antioxidant properties,
      and C-reactive protein (CRP), a marker of inflammation, in acute coronary
      syndromes (ACS) regarding their relationship to cardiac troponins and creatine
      kinase-MB mass (CK-MBm), important prognostic markers. Serum trace elements, GPx
      activity and CRP were determined in 70 patients with ACS who were admitted within
      12 h after the onset. Differences in these parameters were evaluated in three
      groups of patients divided according to the levels of cardiac markers: group III
      consisted of patients with high increases in cTnT, cTnI and CK-MBm (> or =0.9
      ng/mL, > or =1.0 ng/mL, > or =30 ng/mL, respectively), patients with milder
      increases in these markers were included in groups II and I consisted of patients
      with values just above the upper reference limits. Serum Fe levels increased
      significantly in group II and even more prominently in group III compared to
      group I (p = 0.04, 0.002, respectively). There was no significant difference
      between groups II and III. The increase in serum Cu was significant in group III
      compared to both groups II and I (p = 0.04, 0.001, respectively). There was no
      significant difference between groups I and II regarding Cu and Zn. The decrease
      in serum Se and GPx levels was significant only between groups III and I (p =
      0.004 for Se and p = 0.0001 for GPx). CRP levels showed a significant increase in
      group III compared to groups II and I (p = 0.03 and 0.001). CRP showed a
      significant positive and GPx a significant negative correlation to the cardiac
      markers cTnT, cTnI and CK-MBm. Cu was positively correlated to all cardiac
      markers, while the positive correlation between Fe and cardiac markers was
      significant only for cTnI. Both Zn and Se were negatively correlated to cTnT, and
      Se was also to cTnI. In conclusion, the increase in serum levels of Cu and Fe and
      the decrease in serum levels of Zn and Se in patients with higher levels of
      troponins and CK-MBm imply that trace element levels are related to the degree of
      myocardial damage and thus may play a role in the pathogenesis of ischemic heart
      disease. The strong correlations between cardiac markers and both CRP and GPx
      suggest that these parameters are promising prognostic factors in acute coronary
      syndromes.

PMID- 15966571
TI  - Interactions between different selenium compounds and zinc, cadmium and mercury.
AB  - In this paper, we present a polarographic study of systems containing different
      inorganic and organic selenium compounds (sodium selenite, sodium selenate,
      seleno-methionine and seleno-urea) and metal ions (Zn2+, Cd2+ Hg2+) of the 12th
      group of elements in the periodic table. While zinc is a trace element known to
      be essential for plants and animals, cadmium and mercury are exogenous elements
      and are harmful pollutants that accumulate during aging; selenium is also
      recognized as an important micronutrient and is sometimes added to the diet.
      Experiments investigating the interactions were carried out using polarographic
      techniques in unbuffered systems. The three metal cations originated complexes
      with different strength and solubility in the presence of selenite anions; in the
      presence of selenate, polarography was not able to detect formation of complexes
      with these metal ions, at least under the experimental conditions used: a
      decrease of Hg2+ ion concentration was observed. Seleno-methionine did not react
      with Cd2+; in the presence of Zn2+, a soluble complex with a co-ordination number
      1 was formed, while, again, the concentration of Hg2+ decreased in the presence
      of increasing concentrations of the selenium derivative. Seleno-urea did not
      react with Zn2+, but formed a complex with Cd2+ with limited solubility. Finally,
      this ligand could not be studied with Hg2+ because of the overlapping of the
      reduction potentials of both the ligand and the metal cation. Overall equilibrium
      constants for complex formation (Kf) and the solubility product (Ksp) for poorly
      soluble species are also reported.

PMID- 15966573
TI  - Prevalence of zinc deficiency and immune response in short-term hemodialysis.
AB  - Zinc is an essential trace element for many biological functions, including
      immune functions. The mechanism by which zinc may affect the immune system is
      certainly multifaceted, due to zinc's widespread action on different enzymes,
      peptides, transcriptional factors and cytokines involved in the various
      physiological steps of immune development and reactivity. In this study,
      prevalence of zinc deficiency and alteration in complement system,
      immunoglobulins and T cell subsets depending on zinc levels were analyzed in
      short-term hemodialysis patients and compared with healthy controls. Plasma zinc
      levels were measured by flame atomic absorption spectrometry. Serum levels of
      complement C3 and C4, immunoglobulins G (IgG), M (IgM), and A (IgA), and
      prealbumin were measured by nephelometry depending on antigen-antibody reactions.
      Percentages of CD4 and CD8+ were calculated using a flow cytometer. Statistically
      significant decreased zinc levels, especially in the age group > or = 40 years,
      and increased C4, IgA, IgM, IgG and CD4+ levels were observed in hemodialysis
      patients. The prevalence of hypozincemia in hemodialysis patients was found to be
      40%. A higher CD4+/CD8 ratio was also obtained in patients. We conclude that
      patients on maintenance hemodialysis for a short time exhibit zinc deficiency and
      disturbed immune response.

PMID- 15966574
TI  - Zinc has ambiguous effects on chromium (VI)-induced oxidative stress and
      apoptosis.
AB  - Zinc is an important cellular antioxidant. We investigated its role in chromium
      induced oxidative stress and apoptosis in human tumor cell line Hep-2. The
      measured parameters included intracellular labile zinc content (Zinquin-E
      fluorescence), cell viability (WST-1 assay), oxidative stress
      (spectrophotometry), mitochondrial potential (flow cytometry), caspase-3
      activity, and PARP cleavage (immunofluorescence). We found that Hep-2 cells
      contain abundant labile zinc stores that may be depleted by the ionophore TPEN or
      increased by external zinc supplementation. Chromium (VI)-induced cytotoxicity
      and apoptosis were enhanced in zinc-depleted cells after 24 h, in particular at
      chromium (VI) concentrations of 50 and 150 micromol/l. On the other hand,
      elevated levels of labile zinc were able to protect against apoptosis induced by
      10 micromol/l chromium (VI) but at higher chromium (VI) concentrations (50 and
      150 micromol/l) acted synergistically, significantly enhancing oxidative stress
      and the course of apoptosis, possibly through oxidative stress and mitochondrial
      damage.

PMID- 15966575
TI  - Influence of alloxan-induced diabetes and selenite treatment on blood glucose and
      glutathione levels in mice.
AB  - Many clinical studies reported that diabetic patients had lower glutathione
      contents in erythrocytes or plasma. Recently, selenium, an essential trace
      element with well-known antioxidant characteristics, has been found to have
      insulin-mimetic properties. But seldom information is available about the
      influence of selenium on glutathione changes induced by diabetes mellitus in
      animals. Therefore, this study was designed to compare the impacts of selenite
      treatment on glutathione (GSH) levels of blood and tissues such as brain, kidney,
      liver, spleen and testis in mice. Four groups were used in this study: a control
      group, a diabetic group, a selenite-treated normal group and a selenite-treated
      diabetic group. Selenite was administered to the mice for 4 weeks with an oral
      dose of 2 mg kg(-1) day(-1) by gavage. The blood glucose level, and GSH level in
      blood and tissues were determined. The results show that the selenite-treated
      diabetic group had significantly lower blood glucose levels than the diabetic
      group. Moreover, alloxan-induced diabetes significantly decreased GSH levels in
      blood, kidney, liver and testis compared to the controls. Selenite treatment of
      the diabetic mice only improved the GSH levels in liver and brain. On the other
      hand, selenite administered to the normal mice reduced GSH levels in the liver
      compared to the controls. In conclusion, this study suggests that selenite
      treatment of diabetic mice with an effective dose would be beneficial for the
      antioxidant system of liver and brain although it exerts a toxic effect on the
      liver of normal mice.

PMID- 15966576
TI  - Zinc protects HeLa-tat cells against free radical cytotoxicity induced by
      glucose.
AB  - In the present study, we investigated the protective effect of zinc on the
      glucose-induced cytotoxicity in HeLa wild and HeLa-tat cells (30 and 20 mmol/l
      glucose, respectively). HeLa cells transfected with the protein Tat exhibit a
      lower antioxidant defense system. Incubation of HeLa wild and HeLa-tat cells with
      high glucose levels led to a rapid increase in generation of reactive oxygen
      species (ROS). As expected in the presence of high glucose concentrations, the
      viability was reduced for both cell lines. The redox status essentially regulated
      by thiol groups may play an important role in the apoptotic process. Thus, we
      developed a new method using the p-nitrophenyl disulfide to measure cytosolic
      thiol groups in intact cells. Cellular zinc was measured using inductively
      coupled plasma mass spectrometry. Intracellular thiol groups and intracellular
      zinc concentrations were significantly lower in HeLa cells cultured in
      hyperglycemic conditions, and their concentrations were significantly lower in
      HeLa-tat cells than in HeLa wild cells. However, the generation of ROS and the
      induction of apoptosis by a glucose specific mechanism were prevented by zinc (50
      micromol/l) and the intracellular thiol groups and zinc concentrations
      significantly increased in both cell lines to become similar to the initial
      values. These results suggest that the glucose oxidation and its subsequent
      effects on the cells can be prevented by a biological antioxidant such as zinc.

PMID- 15966577
TI  - Review of publications.

PMID- 15966578
TI  - [The reality of health needs adjustment].

PMID- 15966579
TI  - [International Council of Nurses--a strong partner in the struggle against
      tuberculosis].

PMID- 15966581
TI  - [The German Society of Nursing as a WHO collaborating center].

PMID- 15966580
TI  - [Community resolution on obesity].

PMID- 15966582
TI  - [Choosing disposable equipment].

PMID- 15966583
TI  - [A model from Australia].

PMID- 15966584
TI  - [The true future of nurses].

PMID- 15966585
TI  - [Nursing diagnosis is the future. Interview by Jurgen Georg].

PMID- 15966586
TI  - [Nursing process is not put into action. II].

PMID- 15966587
TI  - [Dandelions as an omen of spring].

PMID- 15966588
TI  - [Sick with sick leave].

PMID- 15966589
TI  - [Fresh spices from important cooking?].

PMID- 15966590
TI  - [Towards an ethic for interventional catheterisation in congenital cardiopathy].

PMID- 15966591
TI  - [Non-compaction of the myocardium in childhood].
AB  - Non compaction of the ventricular myocardium is a rare and severe myocardiopathy
      with numerous trabeculations and deep intertrabecular recesses directly connected
      with the ventricular cavity. Many complications may occur: heart failure,
      arrythmia, thrombotic events. However, phenotypic and genotypic presentations
      vary. Non compaction affects infants in almost half of the cases. A pediatric
      national cohort study (directed by the filiale de cardiologie pediatrique de la
      societe francaise de cardiologie) should allow to analyse the clinical and
      epidemiological characteristics of the patients as well as to accurate both non
      compaction's diagnosis and prognosis. Inclusion criteria of this retrospective
      multicenter study were: age lesser than 18, echographic and/or histologic
      criteria of non compaction, no congenital heart disease such as pulmonary
      atresia. This population included 38 patients: 21 were asymptomatic at diagnosis.
      Ten familial forms were detected. The ECG was abnormal in 77% of the cases, the
      chest-X ray in 80%. Echocardiography remains the usual technique for diagnosis.
      However, previously reported quantitative criteria are not easy to use in a
      retrospective study. Treatment was symptomatic as the etiology of non compaction
      is unknown. The prognosis is severe: 31.5% of the patients died or had a cardiac
      transplantation. Only 30% of the patients were free of cardiac events for a 2
      year period. Inclusion of new patients must go on to set up a prospective study
      and biomolecular analysis in informative families.

PMID- 15966592
TI  - [Closure of extrocardiac Fontan fenestration by using the Amplatzer duct
      occluder].
AB  - INTRODUCTION: A direct or tubular communication between the systemic venous
      system and the systemic atrium, generally called fenestration, is surgically
      created to improve the postoperative period of patients undergoing total
      cavopulmonary connection. However, a fenestration prompts a potentially
      deleterious right to left shunt, and is generally closed after the postoperative
      period. Direct fenestrations can be closed using coils, or devices designed for
      atrial septal defect closure. However, no devices have been designed for closure
      of extracardiac fenestrations. We report our experience concerning the closure of
      extracardiac Fontan fenestration by the Amplatzer duct occluder (ADO). METHODS:
      From January 2001 to December 2002, we closed extracardiac Fontan fenestrations
      using the ADO device in 10 consecutive patients. Indications to fenestration
      closure were: low velocity shunt through the fenestration, mild desaturation, and
      absence of effusions. RESULTS: All patients had a successful closure of the
      fenestration. The procedure was performed through the femoral vein in 7 cases and
      through the right jugular vein in 3. Mean central venous pressure increased not
      significantly from 12 to 13-mmHg. Mean oxygen saturation increased significantly
      from 90 to 97% (p<0.001). Immediate shut abolition was obtained in 9 cases. No
      complications were observed. At a median follow-up of 12 months (range 6-18
      months), all patients are free of symptoms and have a normal oxygen saturation at
      rest as well as at exertion. CONCLUSION: The ADO device allowed closing the
      extracardiac Fontan fenestration in all patients with no mortality, no morbidity
      and a rate of 100% of complete closure at mid-term follow-up.

PMID- 15966593
TI  - [Medico-surgical treatment of occlusion of the left pulmonary artery by extension
      of ductal tissue (pulmonary coarctation)].
AB  - The authors report the results of surgical treatment completed by interventional
      catheterisation of occlusion of the left pulmonary artery by extension of ductal
      tissue. Since 2001, 7 patients operated for occlusive coarctation of the left
      pulmonary artery at an average age of 11 months (3 to 37 months) had a
      restenosis. The cardiac malformation was pulmonary atresia with ventricular
      septal defect (N=4), tetralofy of Fallot (N=2) and critical pulmonary valvular
      stenosis (N=1). Pulmonary artery surgery consisted of resection anastomosis in 4
      cases and a plasty in 3 cases. A primary angioplasty was performed 5 to 170
      months (median 12 months) later, at an average age and weight of 3.4 years (0.7
      to 16.9 years) and 14 Kg (8 to 52 Kg) with implantation of 3 stents. The median
      diameter increased from 5 mm (1 to 9 mm) to 10 mm (6 to 16 mm). Tc-99m
      scintigraphy showed an increase in mean left pulmonary perfusion from 9% (6 to
      28%) to 28% (18 to 42%). Secondarily, 3 repeat angioplasties were necessary with
      a total of 6 stents implanted in 7 patients. After an average of 2.9 years (0.8
      to 6.3 years) follow-up, the patients were asymptomatic with normal right
      ventricular pressures and a mean left pulmonary perfusion of 33% (24 to 45%). The
      authors conclude that the treatment of left pulmonary occlusion by coarctation
      requires a medico-surgical approach in which angioplasty and stenting complete
      successfully the surgical revascularisation.

PMID- 15966594
TI  - [Pulmonary atresia with an intact interventricular septum].
AB  - We report this centre's experience of the treatment and follow up of pulmonary
      atresia with an intact septum. 35 infants were seen during the neonatal period.
      Opening via catheterisation was attempted in 21 patients with initial success in
      10, and 11 failures leading to urgent surgery (surgical opening, n=9) and
      isolated Blalock-Taussig anastomosis (n=2). Fourteen other patients underwent
      immediate surgery: surgical opening, n=3, and Blalock alone, n=11. Four patients
      died in the neonatal period: 1 after successful opening via catheterisation, 3
      others after Blalock anastomosis. Five others with a Blalock anastomosis died
      suddenly later. By the end of follow up, 16 patients had undergone biventricular
      type repair, of which 7 required additional procedures. 10 others had undergone
      cavo-pulmonary type repair, including 4 infants in whom the initial strategy of
      biventricular repair had failed. The only predictive factors at birth for
      subsequent progression to biventricular type repair were: larger tricuspid
      diameter at echography (10.9 +/- 2.25 mm versus 6.34 +/- 1.74 mm, p = 0.0007) or
      at angiography (10.07 +/- 2.09 mm versus 8.04 +/- 2.42 mm, p = 0.039), and the
      right ventricular morphology (p = 0.0011) with more tripartite ventricles, and
      less bipartite or even unipartite ones in the biventricular group.

PMID- 15966595
TI  - [Pulmonary atresia with ventricular septal defect and major aortopulmonary
      collateral arteries].
AB  - INTRODUCTION: In order to establish the best strategy of treatment and predictors
      of outcome in infants with pulmonary atresia with ventricular septal defect and
      major aorto-pulmonary collateral arteries, we reviewed our institutional
      experience concerning 47 infants. METHODS: Inclusion criteria included an
      angiographic diagnosis of pulmonary atresia with ventricular septal defect and
      major aorto-pulmonary collateral arteries with or without central pulmonary
      arteries and a repair by the same surgeon. Thirty-one patients had confluent
      (type III) and 16 absent (type IV) central pulmonary arteries. Pulmonary arteries
      were considered to be adequate when they measured > or = 4 mm. RESULTS: There
      were 8 deaths (17%). Complete repair was performed in 24 patients (18 in group
      III and 6 in group IV) with 79.3% had a right/left ventricular pressure <0.5, 16;
      5%<1 and 4.2%>1. Eleven patients are waiting for complete repair and 4 will be
      operated on pulmonary arteries. One stage complete repair was performed in 3
      patients, two and third stage repair (after unifocalisation or right ventricle to
      pulmonary arteries conduit) was attained in 21 patients. Among patients having
      had a complete repair and showing a right/left ventricular pressure <0.5, 88.9%
      had a pulmonary atresia with ventricular septal defect type III and 50% a
      pulmonary atresia with ventricular septal defect type IV. Only 56% of type III
      patients with a right/left ventricular pressure <0.5 had adequate central
      pulmonary arteries. CONCLUSION: In our study, the small size and the absence of
      central pulmonary arteries do not prevent a positive outcome.

PMID- 15966596
TI  - [Paediatric cardiac surgery and autoevaluation: risk score, complexity score and
      graphic analysis].
AB  - The creation of a paediatric surgical unit requires autoevaluation in order to:
      assess the quality of the results with respect to recognised international
      standards, answer the family's questions about the results obtained and adhere to
      criteria of accreditation Between January 2003 and December 2004, 201 consecutive
      patients, children (N= 164) or operated for adult congenital heart disease (N=
      37) were treated. No patient was excluded. The RACHS-1 risk score, the ARISTOTLE
      scores of complexity and performance and the CUSUM and VLAD graphic analyses were
      applied to the study of hospital mortality. An original "variable performance
      adjusted display" (VPAD) graphic analysis was performed to show up any possible
      variations of performance. Paediatric hospital survival was 97.56% (95% CI: 93.9 
      99.1). The paediatric complexity and performance scores were 6.79 +/- 0.22 and
      6.62 respectively. In the absence of statistical significance in this field of
      autoevaluation, graphic analyses indicated the performance of our unit with no
      "learning" curves. Graphic scores and analyses allow assessment of the function
      of a paediatric cardiac surgical unit and the variations of complexity with
      respect to time, before the appearance of statistical significance. The ARISTOTLE
      complexity and performance scores and their adaptation in VPAD seem to be more
      reliable and discriminating than the RACHS-1 score.

PMID- 15966597
TI  - [Surgical repair of atrial septal defect in 1011 consecutive patients].
AB  - The immediate postoperative complications of 1011 consecutive patients undergoing
      surgical repair of atrial septal defects between 1980 and 1998 at Marie
      Lannelongue Hospital were analysedwith the ultimate objective of comparing their
      incidence with that of percutaneous closure. Five patients died (0.49%) of low
      cardiac output (N=3), pulmonary oedema (N=1) or pulmonary hypertension (N=1). A
      total of 356 patients (35.2%) had 448 postoperative complications. There were 77%
      minor and 23% major complications. The minor complications included arrhythmias
      and conduction defects (N=130), respiratory complications (N=90) and pericardial
      effusions (N=64). The main major complications were cardiac failure (N=27),
      cardiac tamponade (N=13), neurological complications (N=8) and reoperation
      (N=28). Of the survivors, 95.6% of patients were discharged from hospital with no
      residual problem and 41 (4.4%) had sequellae: arrhythmias (N=29, including one
      pacemaker implantation), neurological complications (N=4), acquired mitral
      regurgitation (N=2), phrenic nerve paralysis (N=1) and minimal residual shunt
      (N=10). Factors correlated with surgical morbidity were age, the severity of
      pulmonary hypertension, the type of atrial septal defect (less morbidity with
      ostium secundum defects), the presence of associated malformations, the surgical
      approach (less morbidity with the right postero-lateral thoracic approach). This
      study demonstrated the incompressible risk of open heart cardiac surgery. It will
      form a basis for a comparative study of the two modern methods of treating atrial
      septal defect: surgical and percutaneous closure.

PMID- 15966598
TI  - [Results of surgery for coarctation of the aorta in children under one year of
      age].
AB  - The aim of this study was to determine the surgical results of repair of coarcta
      tion of the aorta in children under 1 year of age and to assess the risk of
      recoarctation. Between 1984 and 2004, 206 children under 1 were operated for
      coarctation of the aorta. Three groups of patients were identified: Group I
      (isolated coarctation, N=99), Group II (associated ventricular septal defect,
      N=63), and Group III (complex congenital heart disease, N=44). The transverse
      aorta was hypoplastic in 51% of cases. Uni- and multivariate analysis of the risk
      factors for mortality and recoarctation was performed. An extended resection
      anastomosis was performed in 206 patients. Reconstruction of the transverse aorta
      was performed in 32 cases. The hospital mortality was 3.9% (N=8). The presence of
      a complex intracardiac anomaly was a risk factor for mortality on multivariate
      analysis (p=0.023). In univariate analysis, a two-step management of patients in
      Group III was a significant risk factor for mortality (p=0.036). Thirty patients
      (14.6%) had recoarctation (gradient > 20 mmHg, follow-up 40 +/- 44 months). On
      multivariate analysis the severity of the immediate postoperative gradient was
      the only risk factor for recoarctation. The authors conclude that surgery for
      coarctation of the aorta is associated with excellent results in children under 1
      year of age. The prognosis is related to the presence of associated severe
      cardiac malformations. Survival seems to be better if treatment is carried out in
      a single stage in this group. The risk of recoarctation is related to the
      immediate postoperative transisthmic gradient which justifies extensive repair of
      hypoplastic aortic arches.

PMID- 15966599
TI  - [Extracorporeal assistance in paediatric intensive care].
AB  - OBJECTIVE: For 3 years we have used extracorporeal assistance in intensive care
      frequently. This study evaluates our results. METHOD: We studied the patient
      records for those treated between January 2002 and January 2005. The method used,
      indications and morbidity/mortality were analysed. RESULTS: We performed 24
      circulatory assistance procedures in 20 patients (median age: 5 months), arterio
      venous with oxygenation (n=18), veino-venous with oxygenation (n=3) or
      biventricular (n=3). The indications were post cardiotomy cardio-respiratory
      failure (Group I; n=20, 16 patients), pure respiratory failure (Group II: n=1),
      or pre-transplant/recovery (Group III: n=3). Five procedures (4 from group I and
      1 from group III) required cardiac massage (no fatalities). The average duration
      of assistance was 7 +/- 6 days (2 to 20 days). Treatment was successfully
      discontinued in sixteen patients 80%), one of them thanks to heart transplant.
      Four (20%) died during assistance. The morbidity essentially consisted of further
      surgery for haemostasis, multiple transfusions, and infections. Three patients
      (15%) died later (1 at 17 months after discontinuation) from complications
      unrelated to the assistance. No neurological sequelae were noted in the
      survivors. CONCLUSION: These results confirm the usefulness of circulatory
      assistance when medical treatment has failed, particularly in the post-operative
      period of paediatric cardiac surgery or while awaiting transplantation.

PMID- 15966600
TI  - [Catecholinergic ventricular tachycardia in children].
AB  - Catecholinergic ventricular tachycardia is an adrenergic induced polymorphic
      ventricular arrhythmia. It occurs in infancy and is responsible for syncope and
      sudden death in the absence of any morphological cardiac abnormality. Without
      treatment the mortality in catecholinergic ventricular tachycardia is very high.
      We report genetic and clinical data from 25 cases of catecholinergic ventricular
      tachycardia referred with syncope (n=19) or resuscitated sudden death during
      exercise (n=6). A family history from the 25 families identified 41 apparent
      subjects considered as being clinically affected, with an average age of 30 +/-
      10 years (11 to 62 years). Analysis of the RyR2 gene showed mutations in 13 of
      the 25 cases and in 39 of apparent subjects. With betablocker treatment (nadolol:
      1.6 +/- 0.15 mg/kg), 96% of patients remained asymptomatic over an average follow
      up of between 7.5 +/- 1.5 years, although some of them continued to display
      polymorphic ventricular extrasystoles on exercise. Nevertheless, 12% of the cases
      suffered sudden death or further syncope during follow-up. An automatic
      defibrillator was implanted in 2 patients who had a RyR2 mutation. High dose
      betablockers are effective in preventing serious rhythm disturbance in children.
      In adolescence, implanting an automatic defibrillator should be discussed in
      cases with a history of syncope or resuscitated sudden death. We confirm the
      importance of genetic studies in these families at high risk of sudden death.

PMID- 15966601
TI  - [Outcome of 30 congenital atrio-ventricular blocks].
AB  - Congenital isolated atrio-ventricular block (CAVB) is a rare pathology, and its
      management is still rather poorly described through international literature.
      Within the service of pediatric cardiology leaded by Pr Choussat and Dr Jimenez
      (Cardiologic Hospital Haut-Leveque of Bordeaux), we collected from 1980 to 2003,
      30 isolated congenital CAVB, constituting the purpose of this retrospective
      study. Average follow-up is 14 +/- 8.8 years. None death occurred. CAVB are
      discovered at an average age of 4.8 years old; 6 cases were diagnosed in utero,
      half of them were associated with maternal lupus. Twenty patients on 30 were
      fitted with stimulator at an average age of 8.7 +/- 6.9 years old, due to
      symptoms or bradycardy. Epicardic fitting in VVI mode represents 65% of first
      approaches, it is followed by endocavitary way for 81% of cases. Cardiac
      stimulation does not prevent from dilated cardiomyopathy. Among 30 patients 10
      were not fitted with stimulator, half of them presents chronotrop insufficiency
      during effort. As a conclusion, our patients show a good long-term vital
      prognosis; although CAVB discovered in utero lead to worse prognosis for
      children.

PMID- 15966602
TI  - [Asynchronism and right ventricular pacing].
AB  - In patients with congenital heart block (CHB), dual-chamber pacing restores
      physiological heart rate and atrio-ventricular synchronization. However, patients
      with narrow QRS junctional escape rhythm may be deleteriously affected by long
      term, permanent, apical ventricular pacing. We assessed the impact of apical
      ventricular pacing on echocardiographic ventricular dyssynchrony and hemodynamic
      parameters. METHODS: Fourteen CHB adults (23 +/- years, 58% male), with a DDD
      transvenous pacemaker and a junctional escape rhythm (QRS<120 ms) before
      implantation, were studied. Echocardiography coupled with tissue Doppler imaging
      (TDI) and Strain rate was performed in spontaneous rhythm (VVI mode 30/mn) and
      during atrio-synchronized ventricular pacing. RESULTS: The heart rate (43 +/- 09
      vs 68 +/- 07: p<0.01), cardiac output (2.9 +/- 0.7 vs 3.7 +/- 0.6 L/min) and left
      ventricular filling time (325 +/- 38 vs 412 +/- 51 ms; p<0.01) were significantly
      less in the escape spontaneous rhythm compared with atrio-ventricular
      synchronized apical pacing. However, interventricular dyssynchrony (28 +/- 12 vs
      59 +/- 25 ms, p<0.05), intra-left ventricular dyssynchrony (36 +/- 11 vs 57 +/-
      29 ms; p<0.05), extent of left ventricular myocardium displaying delayed
      longitudinal contraction (26 +/- 10 vs 39 +/- 17%: p<0.05) were significantly
      less in the escape rhythm compared with paced rhythm. CONCLUSION: Once implanted
      with a DDD pacemaker, CHB patients present with increased cardiac output
      secondary to the restoration of physiological heart rate and improved diastolic
      function. However, the apical site is not optimal, as it creates detrimental
      ventricular dyssynchrony in patients with previous nearly physiological
      ventricular activation. Alternative pacing sites should be investigated.

PMID- 15966603
TI  - [Complications of prostaglandin E1 treatment of congenital heart disease in
      paediatric medical intensive care].
AB  - The authors undertook a retrospective study of the modes of prescription, the
      tolerance and efficacy of prostaglandin E1 in 62 consecutive neonates with
      congenital heart disease (average Age 1.6 days: 35 boys: weight: 3.1 +/- 0.6 Kg)
      admitted to the paediatric intensive care unit of Nancy University Hospital
      between 1998 and 2002. The infusion time and cumulative dosage were 134 +/- 112
      (6-480) hours and 111 +/- 94 (4-396) microg/Kg respectively. The side effects
      that were observed were: Apnoea (19%), abdominal distension (16%), bradycardia
      (13%), enterocolitis (6.5%), hypotension (6.5%), vomiting (5%), fever (1.6%) and
      skin rash (1.6%). Gastrointestinal disturbances are associated with a low body
      weight (p<0.04), to prolonged treatment (p<0.02) with no influence of initial or
      cumulative dosages (P=NS), with respiratory assistance (p<0.03) and longer
      hospital stay (p<0.01). Hypotension was commoner in cases of poor neonatal
      adaptation. Mortality was correlated with severe initial acidosis (p<0.02), a low
      Apgar score, the initial prolonged use of high doses of prostaglandin (p<0.04),
      and the presence of severe valvular aortic stenosis or hypoplasia of the left
      heart (p<0.002). The authors conclude that treatment with prostaglandin is
      effective in the majority of cases despite the use of low maintenance doses (0.01
      microg/Kg/min). Gastrointestinal disturbances favourised by the perinatal
      context, the cardiac disease, and prolonged treatment are significant factors for
      morbidity and mortality. The beneficial role of early neonatal enteral feeding
      was not demonstrated in this high risk population.

PMID- 15966604
TI  - [A new approach to the tricuspid valve in Ebstein's anomaly by real time 3D
      echocardiography].
AB  - Ebstein's anomaly affects the tricuspid valve with a large range of anatomical
      forms. Successful tricuspid valvuloplasty depends mainly on the ability to
      mobilise the leaflets. Evaluation of the leaflet surface is difficult with 2D
      echocardiography whereas 3D echocardiography provides intracardiac views of the
      valve. The authors used this method in 10 patients with 3 modes of imaging:
      biplane, real time and total volume. The study population (age: 1 day to 30
      years) included: 1 prenatal diagnosis, 1 neonate with refractory cyanosis, 5
      patients with mild tricuspid regurgitation, 3 patients with severe tricuspid
      regurgitation, 2 of whom underwent valvuloplasty. 3D echocardiography was
      disappointing in the foetus and neonate because of poor spatial resolution. The
      ventricular view of the tricuspid valve in older children and adults allowed
      analysis of tricuspid leaflet coaptation and of the mechanism of regurgitation.
      The commissures and leaflet surfaces were assessed. The results of surgical
      valvuloplasty could be evaluated by 3D echocardiography. 3D echocardiography is
      now transthoracic and a real time investigation. Technical advances are required
      before it comes into routine usage: a more manoeuvrable matricial probe
      (integrating pulsed and continuous wave Doppler) and larger volume real time 3D
      imaging with better resolution. Its role in the assessment of Ebstein's anomaly
      should be evaluated in a larger series of patients.

PMID- 15966605
TI  - [3D echocardiography of the ascending aorta in Marfan's syndrome].
AB  - Marfan's syndrome is a cause of dilatation of the aorta, the main complication of
      which is dissection of the aorta. 2D echocardiography is the reference
      investigation for measuring the ascending aorta. Asymmetry of sinus dilatation
      makes a 3D approach necessary. Real time 3D echocardiography is a simple, non
      invasive method which, by a biplane mode, allows measurement of the 3 sinuses of
      Valsalva. The aim of the study was to compare the 2D and 3D echocardiographic
      methods for measuring the ascending aorta. Fifteen patients (average age 12 +/- 8
      years) with Marfan's syndrome were studied prospectively. The maximal 3D diameter
      was significantly greater than the 2D measurement (31.7 +/- 6.8 mm vs 29.9 +/-
      6.6 mm, p< 0.005). In 4 patients, the difference was over 3 mm. The diameter
      between the right coronary and left coronary sinus was greater than the two
      others (right coronary-non coronary and left coronary-non coronary). The oldest 5
      patients had an MRI aortic measurement very similar to that of 3D
      echocardiography (36.6 vs 36.7 mm). Real time 3D echocardiography in the biplane
      mode enables reliable and reproducible measurement of the aortic root in patients
      with Marfan's syndrome. Larger and multicenter studies are required to allow
      confirmation of the value of 3D echocardiography in the follow-up of these
      patients.

PMID- 15966606
TI  - [Ductus venosus agenesis].
AB  - OBJECTIVE: Congenital absence of the ductus venosus is a rare anomaly in the
      fetus. The aim of our study was to evaluate the clinical and ultrasonographic
      features and outcome of the fetuses with ductus venosus agenesis. STUDY DESIGN:
      We describe 12 cases in the period between 1992 and 2004. The umbilical vein
      drained either into the right atrium directly (2 cases) or by the coronary sinus
      (1 case), or in the inferior vena cava (5 cases), or in the azygos vein (1 case),
      or in the portal vein (3 cases). Our data where analyzed with the cases published
      in the literature. Two groups of anastomoses where defined on the basis of the
      hemodynamic consequences: the group of extrahepatic anastomoses (53 cases) and
      the group of intrahepatic anastomoses (22 cases). RESULTS: In the group of extra
      hepatic anastomoses, cardiomegaly was the most common antenatal finding (39%),
      while in the intra hepatic group hydrops fetalis occurred most frequently (23%).
      Malformation rate was high in both groups (56% and 45%) and chromosomal anomalies
      where present in 9% of cases. CONCLUSION: Careful assessment of the umbilical
      venous return and the ductus venosus should be a part of examination of every
      fetus with cardiomegaly, polyhydramnios, ascites or hydrops. In case of absence
      of the ductus venosus a referral scan, a fetal echocardiography and a karyotype
      should be performed.

PMID- 15966607
TI  - [Linear insertion of the atrioventricular valves without defect].
AB  - On a first anatomical series of 52 hearts of trisomic 21 fetuses, published in
      June 2002, we described a new minor cardiac anomaly, belonging to the
      atrioventricular septal defect, with a linear insertion of the atrioventricular
      valves without defect. We want to confirm these data, on a larger series of 213
      new hearts of trisomic 21 fetuses by adding a complementary section to the
      standard examination; 100% of controls have shown a normal insertion with an
      offsetting of the atrioventricular valves. On 113 out of these 213 hearts of
      trisomic 21 fetuses, with a so called "normal" heart at the standard examination
      showing no defect, the complementary section has shown that only 37.2% of these
      hearts have a normal insertion, whereas 62.83% show a linear insertion, without
      offsetting and without any septal defect. This linear insertion has been observed
      in all the different types of atrioventricular septal defect as a good hallmark
      for trisomy 21; but, since then, they have always been described associated with
      a septal defect, atrial or ventricular. Our hypothesis is that the linear
      insertion of the atrioventricular valves without defect is the minor form of the
      atrioventricular septal defect spectrum, taking place between the prior described
      partial types of atrioventricular septal defect, in which there is always a
      defect (ostium primum type atrial septal defect or inflow type ventricular septal
      defect), and the real normal heart. A precise description of the level of the
      complementary section and of the anatomic peculiarities of the linear insertion
      of the atrioventricular valves without defect would help its screening in fetal
      ultrasonography.

PMID- 15966608
TI  - [Arterial rigidity of patients operated successfully for coarctation of the aorta
      without residual hypertension].
AB  - In patients successfully operated for coarctation of the aorta, the prevalence of
      hypertension is higher than that observed in the general population although the
      exact mechanism is not known. The hypothesis of increased arterial rigidity
      despite satisfactory correction of the coarctation has been proposed. The authors
      undertook 24 hour ambulatory blood pressure monitoring coupled with measurement
      of the QKD interval (pulse wave velocity) in order to evaluate the rigidity of
      the large arteries. These results were compared with those obtained in control
      patients paired with respect to gender, age, height and weight. Twenty-six
      patients with an average age of 14.5 +/- 2.9 years were included (age at time of
      surgery 6.3 +/- 3.7 years). The statistical data confirmed a higher systolic
      blood pressure (p<0.05) in the operated patients compared with controls. The
      results confirm the hypothesis of increased residual arterial rigidity in
      children operated for coarctation of the aorta which could predispose to
      secondary hypertension, especially on effort. In the long term, this could be an
      unquestionable cardiovascular risk factor explaining the increased cardiovascular
      morbid-mortality compared with the general population.

PMID- 15966609
TI  - [Cardiac failure in children].
AB  - The understanding of cardiac failure pathophysiology in children has advanced
      greatly in recent years. Whilst cardiac failure secondary to left ventricular
      dysfunction with viral or metabolic cardiomyopathy is comparable in
      pathophysiological terms with adults, other aetiological mechanisms are also
      implicated, linked both to anatomical anomalies in congenital cardiopathy and
      their surgical repair. The role of the neuroendocrine system with adrenergic
      activation of the renin-angiotensin system, secretion of natriuretic peptides and
      the inflammatory system, before and during surgical repair procedures, have been
      proven both experimentally and clinically. Understanding these pathophysiological
      mechanisms opens new therapeutic perspectives for improving the management of
      children with congenital cardiopathy in cardiac failure and reducing
      postoperative mortality and morbidity.

PMID- 15966610
TI  - [Congenital cardiopathy: indications for anticoagulant treatment].
AB  - Congenital cardiopathy is common in children with thromboembolic disease. There
      are no objective clinical data for medium and long term treatment. Vitamin K
      antagonists could be envisaged for this. Children with a mechanical valve should
      be anticoagulated. This has been validated in adults, there has been no study in
      children which contradicts this, and the serious nature of thromboembolic
      complications in this group is significant. In atrial fibrillation, the most
      frequent indication for oral anticoagulants is after a Fontan procedure, because
      of the thromboembolic risk factors. Anticoagulation following Fontan or similar
      procedures relies on the thrombotic factors and their temporal distribution,
      being more pronounced in the first postoperative year; anticoagulants should be
      given over this period. In Eisenmenger's syndrome haemorrhage is common: these
      patients are not anticoagulated unless there is an indication such as recent
      pulmonary embolus. During interventional catheterisation thromboembolic accidents
      are rare, occurring early, and more commonly with certain prostheses. In adults
      with an intra-atrial prosthesis oral anticoagulants are used for three months,
      and then replaced by antiplatelet drugs. In congenital cardiopathy the stent is
      often pulmonary or aortic, and the incidence of thromboembolic accident is
      therefore very low. For a venous channel or in the context of a Fontan procedure,
      oral anticoagulants are justified for between three and six months. It is to be
      hoped that prospective studies, of which some are in progress, will provide
      further guidance for these indications.

PMID- 15966611
TI  - [Spiral CT scan imaging of the coronary vessels six years after complete repair
      of a Taussig-Bing malformation].
AB  - The Taussig-Bing malformation is a rare form of transposition of the great
      arteries with a ventricular septal defect. Associated cardiac abnormalities are
      common: hypoplasia of the aorta and especially coronary anomalies which may
      complicate surgical repair. The authors report the case of a patient with this
      malformation diagnosed in utero and who underwent anatomical repair on the 11th
      day of life. The coronary anatomy described by the surgeon was type E of Yacoub
      and Radley-Smith's classification. The postoperative course was uncomplicated. At
      the age of 6, a spiral CT scan was performed routinely under betablocker therapy.
      The coronary trajectory with a double loop, the patency of the coronary ostia and
      of the aortic isthmus were accurately demonstrated by this form of imaging.

PMID- 15966612
TI  - [Septal alcoholisation of hypertrophic obstructive cardiomyopathy in childhood].
AB  - The authors report a case of septal alcoholisation in a 6 year old child with
      hypertrophic obstructive cardiomyopathy responsible for congestive cardiac
      failure despite optimal betablocker therapy. The indication was retained in a
      context of mucoviscidosis complicated by multiresistant bacterial infection. At
      catheterisation, the dominant septal artery was identified and an alcoholisation
      was performed by the classic technique described in adults. The immediate result
      was satisfactory with regression of the signs of cardiac failure and reduction of
      70 mmHg of the maximal instantaneous pressure gradient (from 160 to 90 mmHg).
      However, 10 months later, the signs of right heart failure reappeared with a
      partial increase in the maximal instantaneous pressure gradient (100 mmHg)
      leading to surgical myectomy while the patient's condition had considerably
      improved from the pulmonary point of view. Septal alcoholisation would appear to
      be a therapeutic alternative in children especially in cases with a temporary or
      permanent contraindication to conventional surgery.

PMID- 15966613
TI  - [Unusual association of chylopericardium and aortic hypoplasia in a neonate].
AB  - We report the case of a neonate with two very rare anomalies: primary
      chylopericardium and diffuse hypoplasia of the thoraco-abdominal aorta. The
      presentation on the 16th post-natal day was with dyspnoea and refusal to feed.
      The initial clinical examination revealed hepatomegaly and weak femoral pulses.
      2D ultrasound gave a diagnosis of a large compressive pericardial effusion
      combined with moderate hypoplasia of the aortic isthmus. Emergency pericardial
      drainage removed 80ml of chylous liquid. Following prolonged parenteral
      nutrition, the pericardial effusion stabilised. A mechanism of diffuse vascular
      disease affecting the aorta and the lymphatic system is suggested.

PMID- 15966614
TI  - [Acute myocarditis with Toxoplasma gondii. A case report in a newborn].
AB  - Acute myocarditis with Toxoplasma Gondii in immunocompetent patients is rare and
      the paediatric cases touch old children. These myocarditis lead sometimes cardiac
      insufficiency and sometimes mimic a myocardial infarction. The evolution is often
      favorable, even when there is no pest-destroying treatment. We report a case of
      myocarditis toxoplasma Gondii with which has occurred in a 11 month and half old
      infant, whose evolution was favorable with a symptomatic and pest-destroying
      treatment. The interest of this observation is related to the scarcity of acute
      myocarditis caused by toxplasmosis in infant without immunoinsufficiency.

PMID- 15966615
TI  - [Sudden transformation of pulmonary stenosis to trilogy of Fallot in a 65 year
      old patient].
AB  - The authors report the case of a 64 year old woman with typical valvular
      pulmonary stenosis in whom spontaneous and sudden reopening of the foramen ovale
      resulted in cyanosis. Transthoracic echocardiography with injection of contrast
      provides a complete diagnosis: valvular pulmonary stenosis with a mean pressure
      gradient of 83 mmHg and massive right-to-left interatrial shunt. The malformation
      was treated by interventional catheterisation in a two-stage procedure: pulmonary
      valvuloplasty followed by closure of the foramen ovale because of the persistence
      of a right-to-left interatrial shunt. The functional improvement was followed by
      the appearance of effort angina. Coronary angiography showed single vessel
      disease of the left anterior descending artery treated by stenting. The long-term
      outcome was satisfactory.

PMID- 15966616
TI  - [Cardiorespiratory effects of heliox using a model of upper airway obstruction].
AB  - Heliox is a mixture of Oxygen and Helium. The low density of Helium allows this
      mixture to flow in a laminar pattern where oxygen, nitrogen or air flow would be
      turbulent. Therefore the force necessary to move a volume of gas (e.g. Heliox) is
      greatly reduced in comparison to a turbulent gas flow. In a respiratory loading
      experiment we investigated the effects which Heliox exerts on hemodynamic as well
      respiratory variables. 10 volunteers were breathing spontaneously and through
      three different endotracheal (ET-) tubes (ID 4.0, 4.5, 5.0 mm). The subjects were
      switched from room air to Heliox and differences in the variables heart rate
      (HR), blood pressure (BP), stroke volume (SV), stroke index (SI), peripheral
      vascular resistance (TPRI) and left ventricular work index (LVWI) were measured.
      Furthermore the (PhAng) between abdomen and thorax was detected using respiratory
      inductance plethysmography (n=2) and the sense of dyspnoe under the different
      conditions was assessed by the use of a dyspnea score (DS). The means of BP, SV,
      SI, TPRI and LVWI did not significantly differ between the resting and the
      different loading conditions irrespective of the gas that was used. The
      variability of hemodynamic measures was significant larger during loaded vs.
      unloaded breathing. Heliox could significantly reduce this degree of variability.
      In two subjects Heliox could also significantly reduce the PhAng as well as DS.
      Heliox showed effects on hemodynamic as well as respiratory and subjective
      variables. These effects can be interpreted as a reduction of the extent of
      pressure variations in the intrapleural space leading to less impact on
      hemodynamic variables while breathing Heliox vs. room air in a resistive loading
      experiment. In the future the combined measurement of hemodynmic variables as
      well as non-invasive assessment of respiration might shed new light on cardio
      respiratory interaction and effects of Heliox during airway obstruction.

PMID- 15966617
TI  - [The televisit system in patients care after discharge in clinical use--first
      experiences].
AB  - The televisite is a form of application of telemedicine, that allows a
      communication between the patient and the family doctor or specialist in the
      clinic after discharging of hospital. Pioneers for the use of telematic projects
      have been up to now wide states like the USA, Canada, Norway or Australia to
      provide, guarantee and maintain by the means of telemedical solutions medical
      care in geographic regions hardly reachable and of little medical attention. In
      central Europe and Germany telemedicine is gaining in significance on the one
      hand because of increasing importance of the cost factor and resulting pressure
      on the public health system and on the other hand because of the rising demand of
      the patients for optimised medical care. It specially represents a new form of
      treatment in patients care after dischargement of hospital. In the year of 2002 a
      prospective randomised two-armed study was initiated including patients after
      operative intervention by arthroplasty in posttraumatic contracture of the elbow.
      The system of the Televisite is used for 6 weeks after dischargement and patients
      had been controlled ambulant after 6 months including a physical examination. The
      functional outcome will be scored, the duration of stay in hospital measured, the
      arising costs for treatment calculated and the satisfaction of the patients in
      handling the Televisite surveyed. Over this first results showed a shortened stay
      in hospital together with lowered costs in medical treatment on the one hand and
      on the other no difference in functional outcome could be found in comparison to
      the control group by additionally high grade of satisfaction with the new system.

PMID- 15966618
TI  - The critical size bony defect in a small animal for bone healing studies (II):
      implant evolution and surgical technique on a rat's femur.
AB  - In the preclinical field of orthopaedic and trauma surgery critical size bony
      defects (CDS) were used to evaluate the biocompatibility and allow to investigate
      the osteoinductivity and -conductivity of bone substitutes. Concerning the
      anatomical size the laboratory rat indicates a lower limit in small animals which
      are appropriate for experiments on bone. The aim of this study was to define a
      CSD, to develop a suitable fixation system to stabilize bony fragments in CSD and
      to point out the specialities of the surgical technique. These informations
      should help for to design and practice studies concerning bone healing on rat's
      femur. Based on previously acquired anatomical data of rat's femur, the technical
      challenges and anatomical specialities of different osteosynthesis techniques in
      rat's femur surgery are demonstrated. Our experiences with different fixation
      systems and techniques lead to the development of an external fixator, which
      guarantees for a stable bone fragment fixation, prevents severe soft tissue
      damage, allows of a roentgenologic evaluation of the defect zone and prevents
      from undesired direct biomaterial-implant interactions. Neither the proximal nor
      the distal femoral nailing technique is appropriate for a stable fixation in CSD
      of rat's femur. To evaluate the reliability of an own developed external fixator
      42 nude rats with a 4.0 mm CSD were investigated clinically and
      roentgenologically over 10 weeks. The external fixator showed only a small
      implant failure rate. A solid fusion of the bone fragments was not observed
      within the 10 weeks follow-up period.

PMID- 15966619
TI  - Comparison of subtraction arthrography, radionuclide arthrography and
      conventional plain radiography to assess loosening of total knee arthroplasty.
AB  - The value of plain radiographs, digital subtraction arthrography and radionuclide
      arthrography was analysed in 23 cases of failed total knee arthroplasty. The
      preoperative diagnosis was compared with the intraoperative assessment.
      Sensitivity, specificity and the positive and negative predictive value for
      assessing a loose component were determined separately for the femoral and tibial
      components. At revision we found 13 loose femoral and 12 loose tibial implants.
      In eight cases both components were unstable. Plain radiography had a sensitivity
      of 77% for loosening of the femoral and 83% for the tibial component; digital
      subtraction arthrography 77% for the femoral and 8% for the tibial component and
      radionuclide arthrography 31% and 8%. The specificity for plain radiography was
      90% for the femoral and 72% for the tibial implant. For subtraction arthrography
      it was 50% and 82% and for subtraction arthrography 70% and 82%. Radiography had
      the highest positive and negative predictive values for both components compared
      with the other two techniques. As a diagnostic tool to detect implant loosening,
      plain radiography is the most effective in this study. Subtraction arthrography
      and radionuclide arthrography are not suitable for use as routine methods for
      detection of total knee arthroplasty loosening.

PMID- 15966620
TI  - [Effect of vertebral body stiffness before and after vertebroplasty on
      intradiscal pressure].
AB  - Fractures of osteoporotic vertebral bodies are increasingly stabilized with bone
      cement. The effects of vertebral-body stiffness before and after augmentation
      with bone cement and of wedge-shaped vertebral body fractures on intradiscal
      pressure are insufficiently known. In a finite element model of the lumbar spine
      the elastic modulus of cancellous bone as well as the amount and the elastic
      modulus of bone cement were varied and the dependency of intradiscal pressure on
      these parameters was calculated. In addition, a wedge-shaped vertebral-body
      fracture was simulated. The bulge of the vertebral-body endplate and thus the
      intradiscal pressure depends strongly on the grade of osteoporosis in the
      vertebral body. The influence of amount and elastic modulus of bone cement on
      intradiscal pressure is small. A wedge-shaped vertebral-body fracture causes an
      anterior shift of upper-body centre of gravity. If this shift is not compensated,
      it leads to an increased flexion moment that has to be balanced by muscle forces.
      In addition, this shift leads to a stronger increase of intradiscal pressure than
      the augmentation of the vertebral body with bone cement.

PMID- 15966621
TI  - Workflow in the operating room.

PMID- 15966622
TI  - [Cellular radio-based medical knowledge base with sensory interactive mobile
      telephones].

PMID- 15966623
TI  - Following up on evidence-based medicine.

PMID- 15966624
TI  - Low-molecular weight heparin for pulmonary embolism: a shot in the dark?
AB  - Both meta-analyses included large numbers of patients from randomized controlled
      trials with objectively diagnosed PE or VTE. Quinlan has the advantage of only
      including trials of patients with documented PE, which more closely pertains to
      the patient in the clinical question. The study was of excellent quality and
      showed no difference in rates of recurrent PE or mortality. It supports a trend
      towards a decrease in recurrent PE with the use of LMWH vs. UFH, without an
      increased rate of adverse events. The study by van Dongen et al further supports
      the use of LMWH in the combined group of patients with PE or DVT. Van Dongen
      shows a decrease in any symptomatic VTE, major bleeding, and all cause mortality
      in this group.

PMID- 15966625
TI  - Evidence-based practice: what a start and 'Oh, the possibilities'.
AB  - Evidence-based medicine (EBM) was introduced in the early 1990s. In less than 15
      years, it has dramatically changed the way that medicine is practiced and taught.
      Improvements in informatics and evidence resources have helped overcome some of
      the initial problems and allowed busy clinicians to use EBM in practice. Many
      barriers to using EBM still remain. Further work on translating evidence into
      patient care decisions and understanding patients' preferences is required in
      order to realize the improvements that EBM's early proponents envisioned.

PMID- 15966626
TI  - Finding the best available evidence: what's new?
AB  - The voluminous growth of the health literature paired with time constraints of
      practitioners can make it difficult to implement evidence-based medicine (EBM).
      New and better resources that summarize and/or synthesize the literature are
      available to facilitate the integration of evidence into practice. Understanding
      how such resources work and how to use them is an important step in finding
      evidence for patient care. By using a clinical scenario concerning abdominal
      aortic aneurysm screening, this article describes 3 types of EBM resources from
      the "4S" model: systems, synopses, and syntheses. The common features of each
      resource type are discussed and comparisons of selected examples are provided.

PMID- 15966627
TI  - Making evidence-based practice a reality.

PMID- 15966628
TI  - Clinician's guide to systematic reviews and meta-analyses.
AB  - Systematic reviews answer clinical questions by finding and evaluating all
      available evidence. The systematic review is a powerful tool to help clinicians
      use evidence for patient care decisions. There are many sources for high-quality
      systematic reviews. Like all scientific studies there are potential biases, but
      systematic reviews have many benefits over narrative reviews. To ensure
      appropriate use of systematic reviews, clinicians must evaluate them in a
      logical, step-by-step manner. This article will review the benefits of systematic
      reviews, how to locate them, and how to evaluate their quality and results.

PMID- 15966629
TI  - Using clinical practice guidelines to improve patient care.
AB  - Clinical practice guidelines incorporate the best available evidence for the
      management of a disease or an aspect of disease treatment or prevention into a
      single document for health care providers. The quality of practice guidelines has
      improved by adopting standard approaches to the development of guidelines and
      reviewing their quality for use in patient care. Implementing guidelines into
      clinical practice can improve quality and efficiency of care and will likely
      benefit from a multidisciplinary, multifaceted approach.

PMID- 15966630
TI  - Evidence-based medicine for medical students: introducing EBM in a primary care
      rotation.
AB  - BACKGROUND AND OBJECTIVES: Evidence-based medicine (EBM) seeks to improve
      patients' lives by applying the best available evidence to decisions affecting
      health outcomes. Since medical students often do not appreciate the value of an
      evidence-based approach to medicine when they enter third-year clinical training,
      a curriculum was developed introducing third-year students to the practice of EBM
      during a primary care clinical rotation. METHODS: Twenty-seven students over 4
      rotations participated in the series of 6 hour-long seminars, and 8 items from a
      27-item questionnaire were used to measure the impact on students' self reported
      understanding and use of EBM. RESULTS: Responses to questionnaires given before
      and after completion of the curriculum documented improved self-reported
      understanding of EBM and improved self-reported comfort with critical appraisal.
      CONCLUSIONS: A seminar series introducing EBM in a primary care rotation improved
      students' familiarity with and receptivity to use of EBM.

PMID- 15966631
TI  - Meningococcal disease incidence and mortality in Wisconsin, 1993-2002.
AB  - Neisseria meningitidis is a major cause of sepsis and meningitis in children and
      young adults in the United States. To examine recent epidemiologic features of
      meningococcal disease in Wisconsin, we evaluated Wisconsin case surveillance data
      collected during 1993-2002. Surveillance data for cases with onsets during this
      time were analyzed; statistical trends were assessed. Mortality was examined with
      regard to age, sex, serogroup, college student status, and young adult status by
      unadjusted and adjusted analyses. During 1993-2002, 462 cases of meningococcal
      disease were reported in Wisconsin; 55% of case patients were aged < 19 years.
      The annual incidence was 0.9 cases per 100,000 persons per year, and incidence
      was highest among children aged <2 years. Two seasonal peaks in cases were
      observed during January-April and September-October. The annual mortality rate
      during the 10-year interval was 0.09 deaths per 100,000 persons per year.
      Adjusted analysis indicated that serogroup C infection, young adult, and college
      student status (but not sex) were associated with mortality. Meningococcal
      disease remains uncommon and sporadic in Wisconsin. Incidence and mortality rates
      are highest among young children, but young adults who acquire the disease appear
      to be at an increased mortality risk.

PMID- 15966632
TI  - Transcatheter closure of atrial septal defect (secundum type): the role of
      echocardiography in evaluating interatrial defects.
AB  - Atrial septal defects are among the most common congenital heart defects seen in
      the adult population. The diagnosis is usually made in children and closure is
      attempted before they are school age. In other cases, where the diagnosis is
      missed until adulthood, atrial arrhythmias and congestive heart failure are
      commonly seen. We report the case of an atrial septal defect (secundum type),
      which was diagnosed in a 72-year-old woman with paroxysmal atrial fibrillation.
      She also had a history of hypertension and hyperlipidemia. Transthoracic and
      transesophageal findings were consistent with right-sided volume overload and an
      atrial septal defect of approximately 1 cm in size. This was corroborated by the
      findings on cardiac catheterization with a shunt ratio of 1.8. The pulmonary
      artery pressures were within normal limits. The patient was referred for closure
      of the atrial septal defect. Presently, the options for septal defect closure are
      direct suture repair, Dacron patch repair depending on the size of the defect,
      and percutaneous transcatheter closure. Transcatheter closure is also available
      in treating selected patients with patent foramen ovale.

PMID- 15966633
TI  - Communicating evidence: the final frontier.

PMID- 15966634
TI  - Teaching, integrating and enhancing EBM.

PMID- 15966635
TI  - The DEA issues new clarification regarding prescribing schedule II controlled
      substances.

PMID- 15966636
TI  - Meeting the mandate for the HIPAA security rule: are you ready?

PMID- 15966637
TI  - A gift for their lifetime: helping your grandchildren pay for college.

PMID- 15966638
TI  - Spreading the practice of evidence-based medicine: MetaStar's raison d'etre.

PMID- 15966639
TI  - General practice in Northern Wisconsin. 1905.

PMID- 15966640
TI  - A concern that cannot weight.

PMID- 15966641
TI  - Controlling oral and pharyngeal cancer. Can dental professionals make a
      difference?

PMID- 15966642
TI  - Kudos for 'ethical moment'.

PMID- 15966643
TI  - 35-millimeter photography.

PMID- 15966644
TI  - It's not insurance.

PMID- 15966645
TI  - Endodontics.

PMID- 15966646
TI  - Preventing and detecting oral cancer. Oral health care providers' readiness to
      provide health behavior counseling and oral cancer examinations.
AB  - BACKGROUND: The authors conducted a study to examine oral cancer prevention and
      early detection practice patterns in a population-based random sample of
      practicing oral health care professionals in New York state. METHODS: The authors
      surveyed a population-based, self-weighting, stratified random sample of dentists
      (n = 1,025) and dental hygienists (n = 1,025) in New York state. They assessed
      the subjects' readiness to offer tobacco-use cessation and alcohol-abuse
      counseling and oral cancer examinations. RESULTS: The effective response rates
      were 55 and 66 percent for dentists and dental hygienists, respectively. In terms
      of readiness to perform oral cancer examinations for patients aged 40 years and
      older, the large majority (82 percent of dentists and 72 percent of dental
      hygienists) were in the maintenance stage of behavior, indicating that oral
      cancer examinations were a routine part of their practice. In terms of readiness
      to offer tobacco-use cessation counseling, only 12 percent of dentists and 21
      percent of dental hygienists were in the maintenance stage, and only 2 percent of
      dentists and 4 percent of dental hygienists were in the maintenance stage of
      offering alcohol-abuse counseling. CONCLUSIONS: Oral cancer examinations seem to
      have been adopted as a standard of practice by most oral health care providers in
      New York state, but cancer prevention services, such as counseling regarding
      cessation of tobacco use and alcohol abuse, are lacking. CLINICAL IMPLICATIONS:
      Oral health care providers should be trained in oral cancer prevention services
      such as tobacco-use cessation and alcohol-abuse counseling and encouraged to
      include these services, along with continued provision of oral cancer
      examinations, as a standard aspect of care.

PMID- 15966647
TI  - Knowledge of oral cancer risk factors and diagnostic concepts among North
      Carolina dentists. Implications for diagnosis and referral.
AB  - BACKGROUND: Dentists play a critical role in the early detection of oral and
      pharyngeal cancer (OPC). The authors administered a survey that assessed the
      level of knowledge among dentists regarding risk factors and diagnostic concepts.
      METHODS: In 2002, the authors mailed a 38-item, pretested survey to a random
      sample of 1,115 licensed dentists practicing in North Carolina. Three-level (low,
      medium, high) composite index scores for knowledge of risk factors and diagnostic
      concepts were created using previously developed scales. The authors formulated
      multivariable models for risk factor and diagnostic knowledge indexes. RESULTS:
      Of the 584 respondents, only 181 (31 percent) had consistent medium-to-high
      levels of knowledge on both highly correlated indexes. Dentists who had higher
      risk factor and diagnostic knowledge scores were significantly (P < .05) more
      likely to have heard of one or more diagnostic aids (odds ratio [OR], 2.7), to
      have graduated from dental school within the previous 20 years (OR, 1.8) and to
      have performed biopsies or referred five or more patients with suspicious lesions
      per year (OR, 1.7 and 1.5, respectively) than were less-knowledgeable
      respondents. CONCLUSIONS: More education is needed in dental schools,
      postgraduate programs and continuing education programs to enhance dental
      professionals' knowledge of OPC risk factors and diagnostic concepts. Such
      programs should include information about adjunctive diagnostic aids. PRACTICE
      IMPLICATIONS: Greater knowledge of risk factors and diagnostic concepts may
      result in more frequent patient referrals, biopsy procedures or both, thus aiding
      in the early diagnosis and treatment of patients with OPC.

PMID- 15966648
TI  - A review of the management of endodontically treated teeth. Post, core and the
      final restoration.
AB  - BACKGROUND: The clinical decision as to whether an endodontically treated (ET)
      tooth requires a post and a crown poses a challenge to dental practitioners. The
      author conducted a review of the principles for the use of post and core and the
      newer materials such as ceramic and fiber-reinforced posts. TYPES OF STUDIES
      REVIEWED: Using a MEDLINE search and resulting cross-references, the author
      selected original research articles and previous review articles on the topic of
      ET teeth, as well as that of post and core. RESULTS: The author reviewed the
      principles for the use of posts in terms of when it is necessary to use a post,
      different types of posts, various post materials and designs. He also reviewed
      the criteria and technique for post space preparation and post cementation.
      Finally, he discussed the principles of core buildup, as well as options for the
      final restorations. CLINICAL IMPLICATIONS: The author provides a review of the
      principles for the use of post and core, crowns and the different materials
      available today to help clinicians make a clinical decision based on sound
      evidence.

PMID- 15966649
TI  - The psychosocial impact of developmental dental defects in people with hereditary
      amelogenesis imperfecta.
AB  - BACKGROUND: Amelogenesis imperfecta (AI) is a hereditary dental condition with
      poor esthetics and dental sensitivity that frequently requires extensive dental
      treatment. The authors hypothesized that AI is associated with a negative
      psychosocial outcome. METHODS: Family members with and without AI completed a
      questionnaire including demographic and dental history questions, as well as a
      number of psychometric scales. The authors investigated the effects of AI status
      (with versus without), sex and age on each of the psychosocial outcomes using a
      generalized linear model. RESULTS: Subjects with AI (n = 30) had higher levels of
      social avoidance and distress, as well as higher levels of dysfunction,
      discomfort and disability attributable to their oral condition compared with
      subjects without AI (n = 29). The relationship of AI status to fear of negative
      evaluation, mastery and self-esteem was age-dependent. Younger subjects with AI
      tended to have higher fear of negative evaluation scores, while older subjects
      without AI tended to have higher fear of negative evaluation scores.
      Additionally, subjects without AI showed a definite decrease in mastery and self
      esteem scores with age, while subjects with AI tended to show an increase in
      mastery and self-esteem scores with age. CONCLUSIONS: These results indicate that
      having AI has a marked impact on the psychosocial health of affected people
      comparable with the impact of systemic health conditions, especially at younger
      ages. CLINICAL IMPLICATIONS: Dental coverage for AI traditionally is excluded by
      third-party payers as being solely for esthetic reasons. The authors' study shows
      that AI has marked psychosocial effects, which suggests that dental treatment
      could be medically necessary and has far-reaching implications for the affected
      person's overall health.

PMID- 15966650
TI  - New dental findings in the median cleft facial syndrome.
AB  - BACKGROUND: The main features of median cleft facial syndrome are hypertelorism,
      cranium bifidum occultum, widow's peak, and midine clefting of the nose, upper
      lip and palate. Since this pathology was first described in 1967, many cases have
      been reported in the literature, but none of these reports has addressed oral
      anomalies in depth. CASE DESCRIPTION: The authors present the case of a female
      patient aged 4 years and 7 months who was diagnosed with median cleft facial
      syndrome. In this case, the patient had an abnormal number of teeth, owing to
      fusion or agenesis of teeth, supernumerary teeth and ectopic eruption of some
      teeth. These oral anomalies had not been described before in the literature as
      being associated with this syndrome. CLINICAL IMPLICATIONS: Median cleft facial
      syndrome is a rare pathology; however, dentists should know its possible
      alterations at an oral level, because children with this syndrome need dental
      treatment to achieve good esthetics and correct occlusion.

PMID- 15966651
TI  - Ultrasonographic confirmation of carotid artery atheromas diagnosed via panoramic
      radiography.
AB  - BACKGROUND: Studies have shown that panoramic radiographs can capture images of
      calcified atheromas in the internal carotid artery (ICA) in some neurologically
      asymptomatic patients receiving routine dental care. However, the prevalence of
      these hemodynamically significant lesions--that is, those causing greater than 50
      percent vessel lumen occlusion with the consequent heightened risk of stroke--has
      been evaluated rarely. The purpose of this study was to use Doppler
      ultrasonography (DUS) to determine the prevalence of large occlusive lesions
      detected initially via panoramic radiography. Aggressive medical and surgical
      interventions directed toward these large lesions have been shown to moderate the
      risk of stroke. STUDY DESIGN: The authors analyzed the panoramic radiographs of
      1,548 consecutively treated, neurologically asymptomatic dental patients who were
      50 years or older. Those with presumptive atheromas underwent DUS for
      confirmation of the diagnosis and for determination of the degree of stenosis.
      RESULTS: The radiographs of 65 patients (4.2 percent) showed at least one ICA
      atheroma. Thirty-eight patients had bilateral opacities and 27 had unilateral
      opacities. DUS evaluation of the 103 sides of the neck with a radiographically
      identified atheroma revealed that none of the ICAs were normal, 81 (79 percent)
      had less than 50 percent stenosis, 18 (17 percent) had 50 to 69 percent stenosis
      and four (4 percent) had 70 percent or greater stenosis. Four of the ICAs on the
      27 sides without calcifications were deemed normal and 23 had less than 50
      percent stenosis. CONCLUSIONS: These results demonstrate that a subset of
      patients (15 [23 percent] of 65) with an occult atheroma discovered on panoramic
      radiography had significant (> 50 percent) levels of ICA stenosis. CLINICAL
      IMPLICATIONS: Dentists should refer all patients with radiographically identified
      atheromas to a physician for confirmation of the diagnosis and a determination of
      the magnitude of disease, because antiatherogenic interventions have been shown
      to prevent a stroke.

PMID- 15966652
TI  - Pre-endodontic treatment restorations. A modification of the 'donut' technique.

PMID- 15966653
TI  - Removing carious dentin using a polymer instrument without anesthesia versus a
      carbide bur with anesthesia.
AB  - BACKGROUND: The authors describe a new rotary polymer instrument that selectively
      removes infected dentin. This instrument has the potential to prepare selected
      cavities without the need for local anesthesia (LA). Patient acceptance has not
      been investigated in a clinical trial. METHODS: In this open-label clinical
      study, the authors enrolled 20 subjects with two Class I carious lesions and
      randomly assigned them to receive one restoration with the polymer instrument and
      no LA and the second restoration with a carbide bur and LA. Both procedures were
      completed in one appointment. Subjects completed dental history, dental anxiety
      and situational pain questionnaires. At specific points during the procedure,
      subjects rated their perception of the intensity of cold, heat, pain, pressure,
      vibration, fear and anxiety. On completion of the restorative procedures and at
      48-hour and one-week telephone contacts, subjects indicated which procedure they
      preferred. RESULTS: During treatment with the polymer instrument, subjects
      indicated that they experienced slightly more pain, pressure, vibration and
      anxiety, but not more heat, cold or fear. Immediately after the procedure, 14 (70
      percent) of 20 respondents (binomial test; P = .11) said that they would prefer
      having no LA and use of the polymer instrument for future dental work. The number
      of subjects indicating this preference increased to 15 (P < .05) at both the 48
      hour and one-week contacts. One subject requested rescue LA during the polymer
      instrument treatment. CONCLUSIONS: A significant number of subjects preferred the
      rotary polymer instrumentation with no LA to the carbide bur instrumentation with
      LA. They held this preference despite experiencing slightly, but reliably, more
      pain and pressure when treated with the polymer instrument. CLINICAL
      IMPLICATIONS: A polymer (bur-like) rotary instrument with cutting ability limited
      to infected dentin can be used in Class I cavity preparations without the need
      for LA.

PMID- 15966654
TI  - Dental laboratory technology in crisis: the challenges facing the industry.
AB  - Undoubtedly, the four challenges facing dental technology we have described in
      this article are not the only ones, but they are the major ones as identified by
      the participants in the Dental Technology Summit. The attendees conducted active
      discussion on all of these points and developed potential solutions. It was
      gratifying to see the various political and organizational factions agree on the
      challenges, and the participants felt at the conclusion of the conference that
      the described challenges are, in fact, those that need immediate attention. We
      will discuss suggested potential solutions in a column in the June issue of JADA.

PMID- 15966655
TI  - The clinical performance of one- and two-step self-etching adhesive systems at
      one year.
AB  - BACKGROUND: The author compared the clinical performance of a two-step self
      etching adhesive system and a one-step self-etching adhesive system over one
      year. METHODS: Thirty-five patients with noncarious cervical lesions were
      enrolled in the study. The author restored 163 lesions using a two-step (Clearfil
      Protect Bond, Kuraray, Osaka, Japan) or a one-step (Xeno III, Dentsply/DeTrey,
      Konstanz, Germany) self-etching adhesive system. Enamel margins were not beveled,
      and no mechanical retentions were placed. The author evaluted the restorations at
      baseline and at three, six, nine and 12 months after placement using modified
      Ryge criteria for color-matching ability, marginal discoloration, marginal
      adaptation, initial caries formation, anatomical form, postoperative sensitivity
      and retention loss. RESULTS: The author assessed the changes in the parameters
      using the Cochran Q test and the McNemar test at a significance level of .05. At
      one year, the retention rates for the restorations in the two-step group were 100
      percent; they were 96 percent for the restorations in the one-step group. Of the
      retained 75 restorations from the one-step group, two had marginal discoloration
      and slight anatomical form problems. In both groups, color-matching ability and
      postoperative sensitivity remained excellent. CONCLUSION: The performance of both
      self-etching adhesive systems was excellent during this one-year clinical trial.
      However, the two-step system exhibited slightly better retention than the one
      step system. CLINICAL IMPLICATIONS: The one- and two-step self-etching adhesive
      systems evaluated in this study provided excellent clinical retention in
      noncarious lesions without mechanical retention.

PMID- 15966656
TI  - Leadership and team building.
AB  - Leadership is not something that can be done once. It's not a procedure that is
      performed and then you are all set. It is a way of thinking and acting--an
      hourly, daily and annual activity based on desire, skills, training and specific
      behaviors. Dentists who are willing to spend a small amount of time focused on
      leadership inevitably will build better teams with lower turnover and higher
      efficiency.

PMID- 15966657
TI  - Demographics and distribution of dentists in Mississippi: a dental work force
      study.
AB  - BACKGROUND: Many segments of the population experience one or more barriers to
      accessing quality oral health care, including availability of licensed dentists.
      The purpose of the authors' study was to analyze the availability of dentists in
      Mississippi by county over four decades to determine the geographic distribution
      of dentists, shifts in their distribution over time and how this distribution
      relates to population demographics. METHODS: Dentist-to-population ratios were
      determined by county from 1970 through 2000. The authors analyzed these data
      using standardized z scores and geographic information systems (GIS) technology.
      Results are presented graphically and geographically. RESULTS: Results showed
      that 55 counties were designated as dental health professional shortage areas in
      1970, 51 counties in 1980, 30 in 1990 and 40 in 2000. Counties that have a more
      favorable ratio of providers to population were determined, indicating areas in
      which dentists are more likely to practice. CONCLUSIONS: Many geographic areas in
      Mississippi remain underserved. Identifying these areas is a critical first step
      when addressing the current state of Mississippi's dental work force. This type
      of information is useful for decision making as well as responding to the
      population's oral health care needs. PRACTICE IMPLICATIONS: Results of this study
      can assist current and future practicing dentists, dental school administrators
      and policy-makers in making informed decisions for determining suitable practice
      locations, dental school admissions criteria and areas to target for public
      health initiatives. This model also is useful for studying work force disparities
      in other health care professions.

PMID- 15966658
TI  - Court rulings differ on legality of dental MSO agreements.

PMID- 15966659
TI  - For the dental patient. Dealing with dry mouth.

PMID- 15966660
TI  - [Azoospermia: ICSI with synchronous versus non asynchronous testicular sperm
      retrieval].
AB  - We review the improvement made in the management of infertile couples with
      obstructive and non obstructive azoospermia thanks to ICSI. We present the
      difficulties encountered in predicting the presence or the absence of spermatozoa
      in non obstructive azoospermia according to clinical and complementary
      investigations. Testicular biopsy is the only effective test. We recommend the
      practice of non synchronic testicular biopsy and sperm freezing to avoid
      unnecessary ovarian hyperstimulation.

PMID- 15966661
TI  - [The cortico-resistent idiopathic nephrotic syndrome of child. Study of 14
      observations].
AB  - Cortico-resistent nephrosis represent 10% of idiopathic nephrosis in nephrosis in
      children and progresses in almost half of the cases to end-stage renal failure.
      14 cases of cortico-resistant idiopathic nephrotic syndrome, collected over a
      period of 13 years (1990 - 2002), are reported. This study involved 10 boys and 4
      girls, aged 8 years on average. A history of allergy was present in two cases.
      Two other children had a family history of cortico-resistant nephrosis (CRN).
      Consanguinity was found in 6 patients. The diagnosis of cortico-resistant
      idiopathic nephrotic syndrome (CRINS) was suggested by oedema in all cases. Two
      patients had a transitory high blood pressure and 5 others had a macroscopic
      hematuria associated with oedema. Laboratory studies confirmed the diagnosis of
      nephrotic syndrome, which was severe in 10 cases, and revealed a transitory renal
      insufficiency in 5 cases, a hyperlipidemia in 3 cases and signs of
      hyperaldosteronism in 12 cases. Renal biopsy practised in all patients shaved
      small glomerular lesions in 6 cases, a focal and segmental hyalinosis in 8 cases,
      one of which was associated with chronic tubulo-interstitial lesions. Treatment
      was based on alkylant agents in 11 cases (cyclophasplamide in 6 cases and
      chlorambucil in 5 cases) and ciclosparine in 6 cases. 4 years later on average,
      the course was marked by complete remission in one case, relapse of the nephrotic
      syndrome in 3 cases, persistant CRINS without end-stage renal failure in 4 cases
      and progression to end-stage renal failure in 4 cases.

PMID- 15966662
TI  - [Association fibromyoma and pregnancy. About 23 cases].
AB  - The coexistence of leiomyoma and pregnancy may lead to complications with unequal
      gravity. MATERIAL AND METHODS: The authors propose a retrospective study about 23
      cases of association of fibromyoma and pregnancy collected over a period of seven
      years. OBJECTIVES: Study of the effect of fibromyoma on pregnancy and vice-versa.
      Analysis mode of delivery. RESULTS: Aseptic necrobiosis: 21.7%. Urinary tract
      compression: 4.3%. Miscarriage: 13%. Threatened premature birth: 26%. Caesarean
      section: 47.8%. Premature birth: 8.6 %. Neonatal death: nil. CONCLUSION: Maternal
      morbidity due to this association is important. It is essential that pregnant
      women be aware of the importance of prenatal consultation during the first
      trimester of pregnancy.

PMID- 15966663
TI  - [Evaluation of the iron bioavailability from meals prepared with lentil (Lens
      esculenta) or with white kidney bean seeds (Phaseolus vulgaris) in anemic rats].
AB  - The aim of our study was to evaluate the iron bioavailability from lentil seeds
      and white kidney bean seeds. The iron bioavailability from diets was measured in
      rat by the depletion-repletion hemoglobin method and the reserve of iron stored
      in the liver. Our results showed that the iron bioavailability from meal based on
      cooked lentil seeds was significantly low (3.9 +/- 0.9%) as compared to the
      reference group fed with ferrous sulfate (20.4 +/- 4.9%) (p < 0.01) or to the
      group fed with cooked white kidney bean seeds (14.3 +/- 2.4%) (p < 0.01).
      Moreover, the reserve of iron stored in the liver was significantly low in rats
      fed with cooked lentil seeds (80.4 microg) compared to the reference group or to
      the group fed with cooked white kidney bean seeds (99 microg in the two groups, p
      < 0.01).

PMID- 15966664
TI  - [Aspects of outcome and therapy of edematous branch retinal vein occlusion].
AB  - The main cause of oedematous branch retinal vein occlusion (BRVO) vision loss is
      macular oedema persistence. We studied 18 patients having oedematous branch
      retinal vein occlusion. An ophthalmologic exam completed with angiography and
      etiologic assessment were performed. Argon Laser macular grid photocoagulation
      was performed in 11 eyes where macular oedema had persisted for over 3 months
      with visual acuity under 5/10. In 45% of cases, occlusion interests
      superotemporal vein. Atherosclerosis risk factors are found in 88% of cases. The
      course was spontaneously favourable in 39% of cases. Improvement of visual acuity
      was obtained in 36% of cases treated with laser photocoagulation. Oedematous
      branch retinal vein occlusion outcome is variable; it can be favourable if veino
      veinous anastomosis develops rapidly, or unfavourable with macular edema
      persistence and decreased visual acuity. In the later case, grid macular
      phototcoagulation should be performed leading to macular edema regression. So,
      macular edema secondary to branch retinal vein occlusion can disappear
      spontaneously and needs laser treatment only if it persists.

PMID- 15966665
TI  - [Genetic profile of Glanzmann's thrombasthenia in south Tunisia. Report of 17
      cases (11 families)].
AB  - INTRODUCTION: Glanzmann's thrombasthenia (GT) is a rare congenital thrombopathy,
      with a recessive autosomal transmission. We present here the genealogic study of
      a series of patients suffering from GT. PATIENTS AND METHODS: This is a
      retrospective study about all the GT patients treated in Sfax hematology
      department during 18 years. Final diagnosis was established by agregometry.
      Genealogic study was based on clinical history. RESULTS: 17 cases of GT from 11
      families from the south of Tunisia wen collected. The disease was paricularly
      frequent in the region of Moulares-Gafsa (7 patients). The percentage of
      consanguinity was also very high (82%), with a third degree consanguinity of 86%.
      Family investigation revealed 6 previously unknown cases, and 10 deaths
      subsequent to hemorrhagic manifestations. CONCLUSION: The high rate of
      consanguinity, the absence of clinical or biological manifestations in the
      parents, and the ratio of ill to normal subjects in the same family which was
      about one to four, are suggestive of an autosomal recessive mode of transmission.

PMID- 15966666
TI  - [Frequency of esophageal motor disorders in patients with dysphagia and normal
      upper gastro-intestinal endoscopy. A manometric study of 289 cases].
AB  - 289 esophageal manometries performed for 7 years to patients with dysphagia and
      normal upper gastro-intestinal endoscopy were analyzed, excluding patients with
      systemic sclerosis and preoperative manometries for gastroesophageal reflux
      disease. Esophageal motor disorders are frequent in patients with non obstructive
      dysphagia. Esophageal manometry is important to perform in these patients.
      Specific treatment is required in patients with achalasia. Systemic sclerosis and
      gastroesophageal reflux disease should be suspected in patients with esophageal
      hypomotility.

PMID- 15966667
TI  - [Serum lactate dehydrogenase and its isoenzymes in nasopharyngeal carcinoma in
      Tunisia].
AB  - Our prospective study interested 41 patients, from 13 to 70 years old, and
      present a nasopharyngeal carcinoma confirmed histologically, during the period
      going from September 1999 to March 2000, and 45 healthy controls. A blood sample
      was collected from each patient before any treatment, as well as controls to
      measure serum LDH and its isoenzymes. Two groups of patients were selected after
      a period varying from 12 to 37 months with a mean of 29 months: 29 with
      favourable evolution, 12 with non favourable evolution. The mean serum total LDH
      and its isoenzymes values were significantly higher in patients than those in
      controls with values of variable p of 0.001 to 0.05. A significant correlation
      was found between ganglionnary extension and serum values of total LDH, LDH3 and
      LDH5. No significant difference were observed between the means serum total LDH
      before treatment and the clinical evolution of patients. Diagnostic contribution
      of total LDH is limited, by its ubiquitary character, but could constitute for
      LDH3 a good marker of the disease progression.

PMID- 15966668
TI  - [Effects of consanguinity and social factors on mortality and fertility in
      Mauritania].
AB  - This study is to evaluate the consequences of consanguinity and social factors on
      infanto-youthful mortality and fertility in Mauritanian ethno groups. Thereafter
      we studied the correspondence between the methods of all the studied variables.
      The analysis of a sample of 2413 couples obtained according to the quota method
      showed that the infanto-youthful death rate in Soninkes and the Poulard ones was
      higher in the consanguineous groups than in the non consanguineous ones. On the
      other hand, in Maures. Wolofs and black Maures the difference is not significant.
      For all the Mauritanian ethno groups the consanguineous couples had averages of
      fertility significantly higher than those of non consanguineous. Analysis of the
      correspondences revealed two groups. The first was formed by the related ones.
      The second by the non-related ones. Each group formed a unit with other specific
      demographic characteristics.

PMID- 15966669
TI  - [Warty dyskeratoma or "follicular dykeratoma": a clinicopathologic features of a
      new entity].
AB  - INTRODUCTION: Warty dyskeratoma is a rare, benign, epithelial tumor characterized
      by a variable clinicopathologic spectrum. In all cases, lesions revealed foci of
      acantholytic dyskeratosis. CASE REPORT: A 74-year-old man has for two year
      developped a single small nodule with a hyperkeratotic area on the scalp.
      Histopathology revelead a warty dyskeratoma. DISCUSSION: Warty dyskeratoma is an
      epithelial tumor. Histopathology is important for the diagnosis. On the basis of
      our findings and from the literature, we propose to discuss the nosologic problem
      of this entity.

PMID- 15966670
TI  - [Association of systemic lupus erythematosus and dermatopolymyositis].
AB  - Systemic lupus erythematosus (SLE) associated with dermatopolymyositis (DM). This
      association is rare. Diagnosis may be difficult because of their common clinical
      findings. We report here a case. A 22-year-old man was admitted for arthritis
      with fever, diffuse myalgia and periorbital skin heliotrope rash. Electromyogram
      and muscular biopsy were suggestive of DM. The patient was treated with oral
      prednisone. Two months and a half later, he was admitted for impure nephrotic
      syndrome in relation with diffuse proliferative glomerulonephritis. Antibodies
      against native double-stranded- DNA were positive, and normal skin biopsy showed
      immune complex deposit on dermo-epidermic junction, suggestive of SLE. The
      patient was treated with high doses of prednisone and 6 monthly intravenous
      pulses of cyclophosphamide. Skin lesions and nephrotic syndrome improved.
      Presently, the patient remains asymptomatic. While being of different
      pathogenesis, SLE and DM may coexist in the same patient.

PMID- 15966671
TI  - [Intramural small-bowel hematoma due to anticoagulant therapy: a radiologic
      study; with regard to two cases].
AB  - We report two cases of spontaneous small bowel hematoma in two patients receiving
      long-term anticoagulant therapy. Plain abdominal film, ultrasound, CT-scan and
      oral barium examination were performed. Abdominal ultrasonography and CT-scan are
      in most cases relevant for the correct diagnosis of intra-mural small bowel
      hematoma. The diagnosis was based on the acknowledgment by the patient of
      anticoagulant drug consumption. Early diagnosis is crucial because most patients
      are treated nonoperatively with good outcome.

PMID- 15966672
TI  - [Metastatic breast cancer 49 years after initial treatment].
AB  - Very late metastases after cancer therapy are not common. We report an
      exceptionnal case of breast carcinoma associated with pregnancy that reocurred in
      the form of brain metastasis 49 years after initial treatment.

PMID- 15966673
TI  - [Twin pregnancy after renal transplantation: first case reported in Tunisia].
AB  - Women with end-stage renal disease or on regular dialysis have low fertility.
      Renal transplantation restores not only normal renal and endocrine functions but
      also the reproductive function as well and this conception becomes possible.
      Pregnancy in transplanted women is at higher risk and necessitates a
      multidisciplinary follow up. We report the course and out come of two successful
      pregnancies, the second was the first case of twin pregnancy in Tunisia in a
      transplanted woman. Our patient is 35 years old had a chronic renal
      insufficiency, secondary to interstitial nephropathy. After six years of
      hemodialysis, she had received a renal graft from a living donor (his brother). A
      double drug immunosuppression was given (Prednisolone - Azathioprine). Two years
      later, she became pregnant and delivered a normal baby at term, and one year
      later she had a twin pregnancy that ended successfully and delivered by caesarian
      section a two babies with different sex. Pregnancy after renal transplantion must
      be considered as a risk factor for any subsquent pregnancy, and the risk
      nicreases in case of twin pregnancy.

PMID- 15966674
TI  - [Type 1 neurofibromatosis and epilepsy].
AB  - Epilepsy has been rarely reported with type 1 neurofibromatosis (Reckling Hausen
      disease). It may occur in 3 to 6% of cases. We report in this study three cases
      of patients with type 1 neurofibromatosis associated with epilepsy. The patients
      were respectively 23, 30 and 35 years old. Epilepsy was focal and complex in one
      patient, generalized in one case and simply focal in another one. Cerebral MRI
      showed sphenoidal dysplasia and temporal lobe ectopy compressing orbital
      structures in one patient and normal in the other cases. We discuss trough these
      three cases the relationship between Reckling Hausen disease and epilepsy.

PMID- 15966675
TI  - Australia's notifiable diseases status, 2003 annual report of the National
      Notifiable Diseases Surveillance System.
AB  - In 2003, 58 diseases and conditions were notifiable at a national level in
      Australia. States and territories reported a total of 104,956 cases to the
      National Notifiable Diseases Surveillance System an increase of 3.2 per cent on
      the total number of notifications in 2002. In 2003, the most frequently notified
      diseases were sexually acquired infections (38,854, 37% of total notifications),
      gastrointestinal diseases (24,655 notifications, 24%) and bloodborne viruses
      (20,825 notifications, 20%). There were 11,113 notifications of vaccine
      preventable diseases, 6,780 notifications of vectorborne diseases, 1,826
      notification of other bacterial infections and 903 notifications of zoonotic
      diseases.

PMID- 15966676
TI  - Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the World
      Health Organization Western Pacific Region, 2003.
AB  - The World Health Organization Western Pacific Region Gonococcal Antimicrobial
      Surveillance Programme examined over 11,000 isolates of Neisseria gonorrhoeae
      from 13 countries for resistance to antibiotics in 2003. Very high rates of
      resistance to penicillins and quinolones were again present in most centres, but
      little resistance to spectinomycin was detected. Several centres once more
      reported the presence of gonococci with decreased susceptibility to third
      generation cephalosporins. Treatment options for gonococcal disease acquired in
      the Region are increasingly limited.

PMID- 15966677
TI  - Sentinel Chicken Surveillance Program in Australia, July 2003 to June 2004.
AB  - Detection of flavivirus seroconversions in sentinel chicken flocks located in
      four Australian states are used to provide an early warning of increased levels
      of Murray Valley encephalitis virus (MVEV) and Kunjin virus (KUNV) activity in
      the region. During the 2003-2004 season low levels of flavivirus activity were
      detected in northern Australia with both MVEV and KUNV virus activity detected in
      the Kimberley and Pilbara regions of Western Australia and in the Northern
      Territory. A single case of Murray Valley encephalitis was reported from Central
      Australia. MVEV activity was also detected at Minindee in western New South Wales
      for the first time since 2000-2001. No activity was detected in Victoria.

PMID- 15966678
TI  - Influenza surveillance in Victoria, 2004.
AB  - Influenza activity during the traditional Victorian influenza season from May to
      October 2004 was low with no well-defined peak. Surveillance was based on
      sentinel general practice influenza-like illness (ILI) notification with
      laboratory confirmation, locum service ILI notification and laboratory reporting
      of influenza detections. Eight hundred and fifteen consultations for ILI were
      reported from 38 general practices and 216 consultations for ILI were reported
      from the locum service. The average weekly rate of influenza-like-illness from
      sentinel surveillance was 5.4 cases per 1,000 consultations, representing normal
      seasonal activity. Influenza A (H3N2) was the predominant circulating sub-type,
      88 per cent of which were identified as A/Fujian/411/2002-like and 12 per cent as
      A/Wellington/1/2004. All influenza B was B/Shanghai/361/2002-like. There was some
      mismatch with the 2004 influenza vaccine, which contained A/New
      Caledonia/20/99(H1N1)-like virus, A/Fujian/411/2002(H3N2)-like virus, and B/Hong
      Kong/330/2001-like virus.

PMID- 15966679
TI  - A preventable illness? Purulent pericarditis due to Streptococcus pneumoniae
      complicated by haemolytic uraemic syndrome in an infant.
AB  - A previously healthy eight-month-old infant presented with shortness of breath
      and pyrexia. He was found to have purulent pericarditis due to Streptococcus
      pneumoniae, complicated by acute renal failure due to haemolytic uraemic
      syndrome. He received peritoneal dialysis and recovered with normalisation of
      renal function. This case highlights two important complications of pneumococcal
      infection in one individual and illustrates the need for rapid diagnosis and
      treatment of invasive pneumococcal disease. It is anticipated that introduction
      of the conjugate pneumococcal vaccination to the Australian Standard Vaccination
      Schedule from 2005 will reduce the incidence of pneumococcal infection and its
      associated morbidity and mortality.

PMID- 15966680
TI  - An outbreak of measles in Adelaide.

PMID- 15966681
TI  - A cluster of Salmonella Typhimurium phage type U307 associated with a restaurant.

PMID- 15966682
TI  - OzFoodNet: enhancing foodborne disease surveillance across Australia: quarterly
      report, October to December 2004.

PMID- 15966683
TI  - A report from the Communicable Diseases Network Australia October - December
      2004.

PMID- 15966685
TI  - Communicable diseases surveillance.

PMID- 15966684
TI  - Surveillance systems reported in Communicable Diseases Intelligence, 2005.

PMID- 15966686
TI  - An autopsy case of infectious endocarditis in a methamphetamine abuser usefulness
      of microbiological examination.
AB  - We present here a case of sepsis due to infectious endocarditis in a
      methamphetamine abuser. A 32 year-old male presented high fever and abdominal
      pain last two weeks. He was admitted to the hospital on the diagnosis of
      infectious endocarditis. In the evening on the day of admission, he suddenly
      collapsed. Despite of cardiopulmonary resuscitation, his death was confirmed.
      From the autopsy findings, toxicological analysis and results of the
      microbiological examination, we concluded that the cause of death was septic
      shock due to infectious endocarditis, presumably based on the methamphetamine
      abuse. The result obtained from microbiological examination gave us useful
      information. We shall have to be on the lookout, not only for acute poisoning,
      but also for cases of drug abuse related deaths.

PMID- 15966687
TI  - History of forensic medicine. First part: General sources of forensic medicine in
      Europe from the ancient times.

PMID- 15966688
TI  - [Fractures of the facial skeleton after brachial violence].
AB  - The most frequent etiology of fractures of the facial skeleton is criminal
      action, i.e. especially brachial violence. Both mandible and zygomaticomaxillary
      complex are the most afflicted parts of the face. Age group of the 3rd and 4th
      decennium is characteristic for this kind of injury. Assault and battery at night
      is very frequently connected with alcohol consumption.

PMID- 15966689
TI  - Surgical considerations in cochlear implantation in children and adults: a review
      of 342 cases in Vienna.
AB  - CONCLUSIONS: Our data represent the experience of the largest cochlear implant
      program in Austria. In conclusion, cochlear implantation is a safe procedure,
      associated with a low rate of intra- and postoperative complications.
      Nevertheless, patients should be informed about possible problems and especially
      about the risk of a reoperation due to device failure. OBJECTIVES: To evaluate
      the cause of deafness, the intraoperative findings and the complication rate for
      all cochlear implant operations performed consecutively between 1994 and 2003 at
      Vienna General Hospital. MATERIAL AND METHODS: Including all surgeries for
      bilateral implantation and revision, a series of 342 operations performed on 164
      adults (age range 14.5-81 years; mean age 50.79 years) and 128 children (age
      range 0.75-14 years; mean age 5.00 years) was retrospectively analyzed. RESULTS:
      The etiology of deafness was predominantly congenital or progressive (66.89%).
      The routine mastoidectomy approach was chosen in 300 patients (87.72%) and the
      suprameatal approach in 42 (12.28%). Intraoperatively, 4 children (2.53%) had a
      cerebrospinal fluid fistula and 35 patients (10.23%) showed cochlear
      ossification. Three adults (1.63%) and two children (1.27%) had facial nerves
      with an aberrant course. The overall complication rate was 12.2%, the rate of
      major complications was 4.97% and the rate of minor complications was 4.09%.
      There were no cases of either postoperative meningitis or facial nerve palsy.
      Both flap necrosis and electrode dislocation occurred in one adult patient
      (0.54%), but in none of the children. Formation of cholesteatoma was found in one
      adult (0.54%) and one child (0.63%). The rate of device failure was 7.07% for
      adults and 13.92% for children.

PMID- 15966690
TI  - Prevention of impulse noise-induced hearing loss with antioxidants.
AB  - CONCLUSION: These findings indicate a strong protective effect of ALCAR and NAC
      on impulse noise-induced cochlear damage, and suggest the feasibility of using
      clinically available antioxidant compounds to protect the ear from acute acoustic
      injury. OBJECTIVE: Reactive oxygen species have been shown to play a significant
      role in noise-induced hearing loss. In the current study, the protective effects
      of two antioxidants, acetyl-L-carnitine (ALCAR) and N-L-acetylcysteine (NAC),
      were investigated in a chinchilla model of hearing loss resulting from impulse
      noise. It was hypothesized that pre- and post-treatment with these antioxidants
      would ameliorate the effects of impulse noise compared to saline-treated
      controls. MATERIAL AND METHODS: Eighteen animals were randomly assigned to 1 of 3
      groups and exposed to impulse noise at a level of 155 dB peak SPL for 150
      repetitions. ALCAR or NAC were administered twice daily (b.i.d.) for 2 days and 1
      h prior to and 1 h following noise exposure, and then b.i.d. for the following 2
      days. For the control group, saline was injected at the same time points.
      Auditory brainstem responses (ABRs) were recorded. Cochlear surface preparations
      were made to obtain cytocochleograms. RESULTS: Three weeks after exposure,
      permanent threshold shifts for the experimental groups were significantly reduced
      to approximately = 10-30 dB less than that for the control group (p < 0.01). Less
      hair cell loss was also observed in the ALCAR and NAC groups than in the control
      group.

PMID- 15966691
TI  - Characterization of inhibitor of differentiation (Id3) gene expression in the
      developing cochlear tissue of rats.
AB  - CONCLUSION: The Id3 gene is expressed in the developing cochlear tissue and
      participates in the development of cochlear progenitor hair cells during the
      embryonic stage. OBJECTIVES: Inhibitor of differentiation (Id3) is an important
      transcription factor expressed in the cochlear tissue and progenitor hair cells.
      It is likely to be involved in cell-cycle progression and the proliferation of
      cochlear progenitor hair cells during the embryonic stage. The dynamic expression
      of Id3 in the developing cochlear tissue is, however, poorly understood. In this
      study we sought to characterize the expression of Id3 in the developing cochlear
      tissue and to explore its role in the growth and proliferation of progenitor hair
      cells. MATERIAL AND METHODS: Expression of the Id3 gene in the developing
      cochlear tissue was examined by means of Northern blotting, in situ hybridization
      and immunohistochemistry. The effects of Id3 on primary cultures of otocyst
      epithelial cells and a progenitor hair cell line (OT12) were studied using
      specific antisense oligonucleotides. RESULTS: The Id3 gene was expressed in the
      rapidly growing otocyst on embryonic Day 12 and specifically in the fundamental
      structures of the cochlea, e.g. the organ of Corti, spiral ganglions and stria
      vascularis, on postnatal Day 1. Inhibition of Id3 gene expression with antisense
      oligonucleotides in cultured otocyst epithelial cells and OT12 reduced DNA
      synthesis and cell-cycle progression, suggesting that Id3 participates in the
      proliferation of cochlear progenitor hair cells.

PMID- 15966692
TI  - Hearing loss after "refractory" secretory otitis media.
AB  - CONCLUSIONS: The results indicate that SOM of extreme duration, and maybe also
      the treatment of SOM, are risk factors for developing permanent hearing loss,
      both conductive and sensorineural. OBJECTIVE: Fluctuating or persisting hearing
      loss of varying degrees is known to accompany secretory otitis media (SOM). The
      aim of this study was to detect possible hearing sequelae in young adults who had
      suffered from "refractory" SOM during childhood. MATERIAL AND MEDTHODS: A total
      of 33 subjects (age 16-25 years) with previous SOM that had persisted for a mean
      of 11 years (range 6-19 years) were retrospectively examined at a mean of 18
      years after their first myringotomy or tube insertion and compared to 15 healthy
      controls. The follow-up included audiometric examinations (pure-tone audiometry,
      distorted speech and impedance audiometry), otomicroscopy and scrutiny of medical
      records. RESULTS: The SOM group had poorer hearing at all frequencies with the
      exception of 1.5 kHz in the range 0.125-16 kHz. Those with the greatest number of
      myringotomies and tube insertions and those with the longest duration of SOM had
      significantly poorer hearing at high frequencies (8-16 kHz) than those with fewer
      tube insertions and a shorter duration of SOM. The SOM group scored lower on
      distorted speech tests than the controls.

PMID- 15966693
TI  - Effect of recombinant vascular endothelial growth factor on experimental otitis
      media with effusion.
AB  - CONCLUSION: This study demonstrates that rVEGF in the middle ear cavity
      contributes significantly to the development of OME by increasing the vascular
      permeability of the middle ear mucosa. OBJECTIVE: Vascular endothelial growth
      factor (VEGF) has been detected in otitis media with effusion (OME). It has a
      very strong effect on increasing vascular permeability, and is much more potent
      than platelet-activating factor, arachidonic acid metabolites or histamine. The
      purpose of this study was to investigate whether recombinant VEGF (rVEGF) can
      increase vascular permeability in the middle ear mucosa of rats. MATERIAL AND
      METHODS: rVEGF was injected transtympanically at doses of 0.01, 0.1 and 1.0
      microg in the experimental groups; normal saline was injected in the control
      group. Twenty-four h after the injection of rVEGF, middle ear fluid was aspirated
      and the vascular permeability of the middle ear mucosa was measured by means of
      the Evans Blue vital dye technique. RESULTS: Extravasation of Evans Blue dye was
      found in all specimens injected with rVEGF, and was quantified using a
      spectrophotometer. Middle ear fluid developed in all ears injected with 0.1 or
      1.0 microg of rVEGF and histopathology of the middle ear mucosa revealed severe
      inflammatory cellular infiltration, subepithelial edema and vascular dilatation.
      Rats injected with 1.0 microg of rVEGF showed a significant increase in middle
      ear vascular permeability in comparison with the control group (p < 0.05).

PMID- 15966694
TI  - IL-1beta promotes the ciliogenesis of human middle ear epithelial cells: possible
      linkage with the expression of mucin gene 8.
AB  - CONCLUSIONS: These findings suggest that IL-1beta, increases ciliogenesis in
      NHMEE cells and that MUC8 protein may play a role in this process. OBJECTIVES:
      The morphology of the middle ear epithelium changes under various pathologic
      conditions. We compared the density of ciliated cells and the level of mucin gene
      8 (MUC8) mRNA in the middle ear epithelial cells of mucoid otitis media (MOM)
      patients with those of normal controls. We also investigated the effect of IL
      1beta on the ciliogenesis and expression of MUC8 mRNA in cultured normal human
      middle ear epithelial (NHMEE) cells. In addition, we localized the MUC8 protein
      in cultured NHMEE cells. MATERIAL AND METHODS: The surface morphology of NHMEE
      cells was examined using scanning electron microscopy. Reverse transcriptase
      polymerase chain reaction was performed to determine the level of MUC8 mRNA
      expression. After synthesis of MUC8 polyclonal antibody, we performed
      immunohistochemical staining. RESULTS: The density of ciliated cells was
      increased in the middle ear epithelium of both MOM patients and IL-1beta-treated
      cultures. Similarly, the expression of MUC8 was increased in both cases. MUC8
      antibody was primarily stained on the ciliated cells of NHMEE cells.

PMID- 15966695
TI  - Pseudomonas aeruginosa infection in the hypoventilated middle ear: an
      experimental model.
AB  - CONCLUSION: This is a suitable model for studying different aspects of the
      pathophysiology of chronic suppurative otitis media. OBJECTIVE: To analyze the
      methodological features of an animal model of chronic suppurative otitis media
      induced by intratympanic inoculation of Pseudomonas aeruginosa. MATERIAL AND
      METHODS: Otitis media was induced by inoculation of P. aeruginosa through the
      inferior aspect of the rat bulla and cauterization of the Eustachian tube via a
      transpalatal approach. Inspection of the tympanic membrane, culturing of middle
      ear effusion and processing of the temporal bones for light microscopy were
      performed. RESULTS: Abnormal otomicroscopic findings and persistence of infection
      were correlated with the histopathological changes found in middle ear tissues.

PMID- 15966696
TI  - Experience of handicap and anxiety in phobic postural vertigo.
AB  - CONCLUSIONS: We found a difference in gender distribution in a population of
      phobic postural vertigo patients compared with dizzy patients seen in general
      neuro-otological practice. It appears as if women with phobic postural vertigo
      suffer more and are more handicapped by dizziness than both men with phobic
      postural vertigo and a population with dizziness. These differences may reflect
      other causes of phobic postural vertigo besides anxiety, such as gender-related
      coping behaviour and postural strategy. OBJECTIVE: Anxiety influences the degree
      of suffering and handicap in dizzy patients. Experiences of anxiety and handicap
      were investigated among a population with phobic postural vertigo. MATERIAL AND
      METHODS: Using the Dizziness Handicap Inventory, the Vertigo Symptom Scale and
      the Vertigo Handicap Questionnaire, 34 consecutive patients with phobic postural
      vertigo were compared with a population of 95 consecutive patients seen at a
      balance disorder clinic. RESULTS: Patients with phobic postural vertigo scored
      higher than the control subjects with respect to all parameters with the
      exception of the physical subscale of the Dizziness Handicap Inventory. Because
      there were significantly more women in the control group we performed a gender
      specific analysis of the results. The higher test scores among patients with
      phobic postural vertigo can be explained by the higher scores among women in this
      group, while the test results for men were more similar to those of the control
      group.

PMID- 15966697
TI  - Migraine-associated vertigo.
AB  - CONCLUSIONS: It is probably not wise to demand a temporal relationship between
      migraine symptoms and vertigo for the definition of migrainous vertigo. When
      recurrent vertigo attacks begin at an early age in a patient with normal hearing
      and migraine, there are few diagnoses other than migraine that need to be
      considered. OBJECTIVE: The clinical association between migraine and vestibular
      symptoms, such as dizziness, motion intolerance and spontaneous attacks of
      vertigo, is well documented. Recently, investigators have attempted to develop
      diagnostic criteria for this association. We hypothesized that there are multiple
      migraine-associated vestibular syndromes and studied a more homogenous subset of
      them (benign recurrent vertigo). MATERIAL AND METHODS: A structured interview was
      conducted over the telephone with 40 patients who presented to our neurotology
      clinic with benign recurrent vertigo and met the International Headache Society
      criteria for migraine. The structured interview was also conducted with 40
      relatives of the patients who reported the same symptoms. RESULTS: A marked
      female predominance was found. Most of the patients had vertigo attacks lasting
      minutes or hours and most were completely free of dizziness between attacks.
      Imbalance and nausea typically accompanied the vertigo. However, in half of the
      cases, vertigo occurred without an association with headache.

PMID- 15966698
TI  - Motion sickness susceptibility associated with visually induced postural
      instability and cardiac autonomic responses in healthy subjects.
AB  - CONCLUSIONS: This study supports the hypothesis that postural sway and autonomic
      responses to moving visual stimuli may be associated with motion sickness
      susceptibility. Characteristics of the cardiac sympathovagal balance during
      exposure to provocative stimulation may be a marker of individual susceptibility
      to motion sickness. OBJECTIVE: To assess the relationship between postural and
      autonomic responses to a simulated visual motion environment and reported
      susceptibility to motion sickness. MATERIAL AND METHODS: Fifteen healthy subjects
      were exposed to sinusoidally oscillating visual motion in roll at frequencies of
      0.1-0.4 Hz. Recordings were made of postural sway and respiratory frequency and
      electrocardiograms were obtained from which heart rate variability (HRV) was
      computed in order to probe cardiac sympathetic and parasympathetic activity.
      RESULTS: In subjects with a low susceptibility to motion sickness as rated using
      a standardized questionnaire, there was no significant effect of visual stimulus
      on postural sway or HRV at any frequency of motion. Subjects with a high
      susceptibility to motion sickness showed significant postural instability induced
      by visual stimuli (p < 0.01). Visual stimuli presented at a frequency of 0.1 Hz
      significantly increased the low-frequency power (LF) of HRV, decreased the high
      frequency power (HF) of HRV and increased the LF:HF ratio in these subjects (p <
      0.05).

PMID- 15966699
TI  - Expression of Na+/H+ exchanger isoforms in normal human nasal epithelial cells
      and functional activity of Na+/H+ exchanger 1 in intracellular pH regulation.
AB  - CONCLUSIONS: Both the mRNA and protein of NHE1, -2 and -3 were expressed in NHNE
      cells. NHE1 is a major NHE isoform which is expressed in the basolateral
      membranes of NHNE cells. OBJECTIVE: Na+/H+ exchangers are ubiquitous plasma
      membrane transport proteins implicated in the maintenance of intracellular pH.
      The aim of this study was to examine the expression of Na+/H+ exchangers as a
      function of the differentiation of normal human nasal epithelial (NHNE) cells. In
      addition, we investigated the functional activity of the Na+/H+ exchanger 1
      (NHE1) in basolateral membranes. MATERIAL AND METHODS: Cultured passage-2 NHNE
      cells were used. RNA and histological samples were collected on the day of
      confluence and on the 7th, 14th and 28th days after confluence in order to
      determine the effects of time. Cell lysates were collected on the day of
      confluence to investigate the presence of the proteins. Reverse transcriptase
      polymerase chain reaction and Western blotting were performed to investigate the
      presence of mRNA and protein, respectively. The functional activity of NHE1 was
      examined using 3-methylsulfonyl-4-piperidinobenzoyl guanidine methanesulfonate
      (HOE694), an NHE1-specific inhibitor, on the day of confluence. RESULTS: The NHE1
      mRNA expression level did not change as a function of differentiation. However,
      the NHE2 mRNA expression levels increased on the 7th, 14th and 28th days after
      confluence. The NHE3 mRNA expression levels increased on the 14th and 28th days
      after confluence. Western blot analysis confirmed the expression of NHE1 (91
      kDa), NHE2 (90 kDa) and NHE3 (93 kDa). In addition, HOE694 inhibited basolateral
      NHE activity by 68% at 1 microM and by 85% at 5 microM in the NHNE cells.

PMID- 15966700
TI  - Selective embolization in the treatment of intractable epistaxis.
AB  - CONCLUSIONS: In skilled hands, selective embolization is a safe procedure and
      represents an effective treatment for prolonged epistaxis. Embolization therapy
      can be repeated if necessary. OBJECTIVE: Severe posterior epistaxis is a common
      clinical problem in an ENT department and controlling the bleeding may present
      difficulties. Several methods are used to control posterior epistaxis, one of the
      latest treatment strategies being selective embolization of the nasal arteries.
      The aim of this study was to describe the effect of selective embolization in 22
      patients treated with a total of 30 procedures at the ENT Department of Odense
      University Hospital between January 1995 and March 2004. To our knowledge this is
      the first Nordic work in which selective embolization has been used as a
      treatment strategy for patients with hereditary hemorrhagic telangiectasia (HHT).
      MATERIAL AND METHODS: This was a retrospective review. Post-treatment effects and
      complications were evaluated by means of a questionnaire and a telephone
      interview. Owing to the different treatment strategies used, the results were
      evaluated for 2 groups of patients: Group A, 9 patients with HHT; and Group B, 13
      patients with causes of epistaxis other than HHT. RESULTS: In Group A, 15
      procedures were performed, 12 of which were beneficial as the duration and number
      of episodes of epistaxis were reduced. In Group B, 15 procedures were performed
      and the success rate was 87%. One patient suffered from skin necrosis at the tip
      of the nose. No other serious side-effects of the treatment were observed.

PMID- 15966701
TI  - Combined nasal-palatopharyngeal surgery for obstructive sleep apnea: simultaneous
      or staged?
AB  - CONCLUSIONS: Our data indicate that surgical outcomes in a simultaneous surgery
      group were equivalent to those in a staged surgery group. The simultaneous type
      of surgery was more cost-effective in terms of total hospitalization expenses.
      OBJECTIVE: To compare the outcomes of two types of combined nasal
      palatopharyngeal surgery (simultaneous and staged) for the treatment of
      obstructive sleep apnea (OSA). MATERIAL AND METHODS: A total of 85 consecutive
      patients were enrolled in the study. All patients had OSA and its associated
      symptoms, were type I according to the Fujita classification, stage 1 or 2
      according to the Friedman classification and had nasal obstruction with nasal
      septal deviation. A modified form of uvulopalatopharyngoplasty (extended
      uvulopalatal flap surgery) and septomeatoplasty were used to correct upper airway
      abnormalities. Patients chose to have either a simultaneous (n = 55) or staged (n
      = 30) type of operation. All patients underwent overnight polysomnography at
      baseline and < or = 6 months after completion of the operations. Surgical results
      (reduction of OSA), patient satisfaction, complications and hospitalization
      expenses were compared between the two groups. RESULTS: The two groups comprised
      body mass index- and respiratory disturbance index (RDI)-matched cohorts (p >
      0.05). Postoperative decreases in RDI were significant in both groups (p <
      0.001), and postoperative RDI was indistinguishable between the two groups (p =
      0.77). Incidences of surgical complications, including tonsillar bleeding, nasal
      septal hematoma, nasal regurgitation and the sensation of a lump in the throat,
      were similar in the two groups (p = 0.35). The simultaneous surgery group
      incurred lower total hospitalization expenses than the staged surgery group (p <
      0.001).

PMID- 15966702
TI  - Effect of a buccal bioadhesive nystatin tablet on the lifetime of a Provox
      silicone tracheoesophageal voice prosthesis.
AB  - CONCLUSION: Daily application of a buccal bioadhesive slow-release nystatin
      tablet (100,000 IU per tablet) significantly increased the voice prosthesis
      lifetime in laryngectomized patients compared to conventional local cleaning of
      the prosthesis with an antimicrobial agent on a brush. OBJECTIVE: To investigate
      the effect of a buccal bioadhesive nystatin tablet on the lifetime of a Provox
      tracheoesophageal voice prosthesis in post-laryngectomy patients. MATERIAL AND
      METHODS: A buccal bioadhesive tablet, based on a spray-dried Amioca/Carbopol 974P
      mixture containing 10% (w/w) Carbopol 974P, was loaded with 100,000 IU of
      nystatin. Patients were included in the study when replacement of their voice
      prosthesis was required and were divided into three groups. Conventional daily
      local cleaning of the voice prosthesis by means of an oral nystatin suspension on
      a brush (Group 1; n = 7) was compared with application of one nystatin buccal
      bioadhesive tablet per day, after breakfast, on the gingiva above the upper
      canine (Group 2; n = 7). The control group (n = 5) used no antimicrobial agents.
      The lifetime of the prosthesis was followed and expressed in days. RESULTS: The
      lifetime of the voice prosthesis was significantly increased in Group 2 compared
      to Group 1 (p < 0.05; paired t-test), indicating that sustained release of
      nystatin in the oral cavity, by means of erosion of the tablet over a period of
      approximately = 8 h, is more effective at preventing microbial colonization of
      the prosthesis than local cleaning.

PMID- 15966703
TI  - Endoglin (CD105) expression in head and neck basaloid squamous cell carcinoma.
AB  - CONCLUSIONS: This comparison of neo-angiogenesis performed by analysing CD105
      expression seems to suggest that the biological behaviour of head and neck BSCCs
      is similar to that of site- and stage-matched conventional SCCs. OBJECTIVE:
      Basaloid squamous cell carcinoma (BSCC) is an uncommon, high-grade biomorphic
      variant of SCC with a predilection for the head and neck region. It is a matter
      of controversy whether the biological and clinical behaviour of BSCC is more
      aggressive than that of SCC. Angiogenesis is essential for tumour growth. It has
      been established that endothelial cells of tumour-associated neovasculature
      proliferate more rapidly than endothelial cells of normal tissue. Endoglin
      (CD105) has been shown to be a useful marker for identifying proliferating
      endothelium involved in tumour angiogenesis. The aim of this study was to
      investigate the expression of CD105 in head and neck BSCCs and to compare it with
      that in SCCs. MATERIAL AND METHODS: Nine head and neck BSCCs (five cases in the
      larynx, three in the tongue and one in the tonsil) were considered. A group of
      nine site- and stage-matched SCCs was examined simultaneously. For each sample,
      CD105 reactivity was evaluated immunohistochemically. The mean area fraction
      (percentage of fields occupied by vessels), the percentage of vessel-presenting
      fields and the vessel density were considered. RESULTS: The median values of the
      mean area fraction were 1.01% and 0.9% in BSCCs and SCCs, respectively. The
      median values of the percentage of vessel-presenting fields were 57.5% and 46.67%
      in BSCCs and SCCs, respectively. The median values of vessel density were 2.07%
      and 1.58% in BSCCs and SCCs, respectively. Statistical analysis did not disclose
      any significant differences between BSCCs and SCCs for any of the above-mentioned
      parameters.

PMID- 15966704
TI  - Superoxide dismutase and glutathione peroxidase enzyme activities in larynx
      carcinoma.
AB  - CONCLUSIONS: It can be concluded that these changes are related to damage at the
      DNA level or to the inhibitory effects of tumor promoters. Increases in GSH-Px
      activities may be related to the independence of this enzyme from the suppressive
      effects of tumor promoters. This study and others in the literature show that it
      is not possible to generalize the activities of SOD and GSH-Px in cancer.
      OBJECTIVE: There has been growing interest in the role of free radicals as a
      cause of cancer. It has been suggested that an increase in activated forms of
      oxygen in cells due to overproduction and/or the inability to destroy them may
      lead to severe damage of cell structures. As a result of these changes, some
      chromosomal aberrations and carcinogenesis may develop. Superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) are two important antioxidant enzymes
      involved in enzymatic antioxidant defense mechanisms. To our knowledge there have
      been no previous studies in the literature investigating the activities of SOD
      and GSH-Px in laryngeal cancer. MATERIAL AND METHODS: The study subjects
      comprised 10 male patients (age range 43-76 years) with laryngeal carcinoma and
      10 healthy controls (4 males, 6 females; age range 40-69 years) with intraoral
      hyperplastic fibrous tissue. Homogenate SOD and GSH-Px activities were measured
      using commercially available kits. RESULTS: GSH-Px levels were significantly
      increased in the cancerous tissues compared with cancer-free adjacent tissues and
      fibrous hyperplasia tissues (p < 0.05), whereas there was no significant
      difference between SOD activities (p > 0.05). There was also no significant
      difference between GSH-Px activity in cancer-free adjacent tissues and fibrous
      hyperplasia tissues (p > 0.05).

PMID- 15966705
TI  - Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation
      of herpes simplex virus type 1.
AB  - CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1
      reactivation in the GG, CD4 + T cells play a more important role in host defense
      against virus replication. OBJECTIVE: To elucidate the host immunological factors
      that participate in herpes simplex virus type 1 (HSV-1) reactivation in the
      geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model
      of facial paralysis that involved the reactivation of HSV-1 following general
      immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary
      facial paralysis caused by inoculating the auricle with HSV-1 the auricle was
      scratched and mice (n = 69) were given an i.p. injection of either anti-CD4 (n =
      46) or anti-CD8 (n = 23) monoclonal antibody to deplete specific T-lymphocyte
      subsets. Following this reactivation procedure, the rate of recurrent facial
      paralysis was compared between the two models. The GG were examined
      histopathologically and using polymerase chain reaction to detect HSV-1 DNA.
      RESULTS: Facial paralysis developed in 42% of mice in the anti-CD4 model and in
      13% in the anti-CD8 model. HSV-1 DNA was detected in 50% of the mice in both
      models. Histopathologically, neurons were destroyed in parts of the GG and
      numerous virus particles were seen in the surviving neurons.

PMID- 15966706
TI  - Inflammatory pseudotumour (plasma cell granuloma) arising in the maxillary sinus.
AB  - CONCLUSIONS: Inflammatory pseudotumours in the maxillary sinus may present as
      malignant tumours and manifest locally aggressive features characteristic of such
      tumours. Despite their locally destructive features, they pursue a benign course
      after local excision. OBJECTIVE: Inflammatory pseudotumour (plasma cell
      granuloma) is an uncommon non-neoplastic lesion comprising a proliferation of
      spindle myofibroblasts and chronic inflammatory cells. Despite its benign
      histopathological nature, it may exhibit aggressive behaviour that is yet to be
      characterized in the head and neck area. MATERIAL AND METHODS: We present the
      cases of two adult patients with inflammatory pseudotumour arising from the
      maxillary sinus. Immunohistochemistry and polymerase chain reaction for
      immunoglobulin from tissue sections were performed to confirm the polyclonality
      of the infiltrating plasma cells. RESULTS: CT and MRI disclosed expansive soft
      masses eroding surrounding soft and bony tissues. Histopathologically, the
      lesions were unencapsulated and composed of numerous plasma cells, histiocytes
      and spindle cells with minimal nuclear pleomorphism.

PMID- 15966707
TI  - An aesthetic deformity: Madelung's disease.
AB  - Madelung's disease, also known as benign symmetric lipomatosis, multiple
      symmetrical lipomatosis or Lanois-Bensaude syndrome, consists of growth of fatty
      masses predominantly on the face, neck, shoulders, upper thorax and arms. These
      painless and symmetrical fatty deposits can cause important aesthetic changes in
      these patients. Middle-aged males are more commonly affected, with an increased
      prevalence in the Mediterranean area. Currently, the incidence in Italy is 1 in
      25,000 males. The aetiology of Madelung's disease remains unknown, although
      approximately = 60% of affected patients are clinically overweight and there is
      an intimate association with chronic alcohol abuse. We report an unusual case of
      Madelung's disease in a 52-year-old male. The fatty deposits were completely
      resected by means of surgical lipectomy. The patient remains well and disease
      free after 12 months of postoperative follow-up.

PMID- 15966708
TI  - A case of high-pitched diplophonia that resolved after a direct pull of the
      lateral cricoarytenoid muscle.
AB  - Various approaches have been employed for the surgical treatment of unilateral
      vocal cord paralysis. Recently, we performed a direct pull of the lateral
      cricoarytenoid muscle in a case of high-pitched diplophonia with little
      difference between the right and left vocal cord levels and obtained favorable
      results. The patient was a 66-year-old male who consulted our hospital with chief
      complaints of husky voice and abnormal sensation in the pharyngolaryngeal region.
      Cerebellum/brainstem inflammation was diagnosed in February 2002 and appropriate
      treatment was instituted. Despite an improvement in the patient's systemic
      condition, right vocal cord paralysis remained. Although there were no
      abnormalities in the vocal range for ordinary speech, diplophonia was noted at
      high pitches, and synchronization could not be observed using stroboscopy.
      Therefore, the patient was operated on in October 2002. The high-pitched
      diplophonia disappeared and stroboscopy revealed favorable mucosal waves at high
      pitches. Thus, direct pulling of the lateral cricoarytenoid muscle appears to be
      a useful procedure, even in a case of mild unilateral vocal cord paralysis.

PMID- 15966709
TI  - Recurrent epistaxis after treatment with tadalafil (Cialis).
AB  - A 66-year-old male presented to our department with recurrent epistaxis. On
      examination it was not possible to identify the source of the bleeding, despite
      various measures. The bleeding stopped spontaneously each time and advice on nose
      bleeds was given to the patient. During a consultation the patient volunteered
      that the trigger for the epistaxis appeared to have been energetic sexual
      activity. To enhance his sexual performance he had taken Viagra; however, on
      stopping the Viagra and changing to the newer drug Cialis, the episodes of
      epistaxis continued. We document what we believe to be the first case of
      epistaxis caused by Cialis.

PMID- 15966710
TI  - Trans lipids: the free radical path.
AB  - Free radical-catalyzed cis-trans isomerization of unsaturated lipids and its
      outcome in biomimetic conditions are reviewed. They provided indications for an
      endogenous origin of trans unsaturated fatty acids in humans by the attack of
      thiyl radicals. A multidisciplinary approach highlights the relevance of this
      topic. The role of cis lipid geometry and its maintenance in the biological
      environment is an emerging question, with future developments in the fields of
      lipidomics, biology, and medicine.

PMID- 15966711
TI  - Chemistry of squaraine-derived materials: near-IR dyes, low band gap systems, and
      cation sensors.
AB  - Squaraines belong to an important class of organic dyes with intense absorption
      and emission properties in the visible to near-IR wavelength range. The optical
      properties of squaraines, which are sensitive to the surrounding medium, make
      them ideal candidates to photophysists to study the excited-state properties and
      to material chemists for designing a variety of materials that are useful for
      wide-ranging applications. The present Account pertains to the recent
      developments in the materials chemistry of squaraines, highlighting our
      contributions to the study of squaraine-based near-IR dyes, low band gap
      polymers, and cation sensors.

PMID- 15966712
TI  - Exploiting synthetic chemistry with mesoionic rings: improvements achieved with
      thioisomunchnones.
AB  - The chemistry of mesoionic rings, especially their use as masked dipoles, has
      been a fruitful area of research since the late 1950s. With recent advances in
      the control of regio- and stereochemistry, the dipolar cycloaddition led to
      widespread application. In this Account, we illustrate our contribution employing
      thioisomunchnones, a class of mesoionics that has found use in creating a series
      of heterocyclic systems hitherto inaccessible by conventional 1,3-dipolar
      cycloaddition. We also provide some rationalizations from computations and
      comment on future directions.

PMID- 15966713
TI  - Lipid--protein interactions revealed by two-photon microscopy and fluorescence
      correlation spectroscopy.
AB  - Cellular processes involve a multitude of chemical reactions that must be kept in
      delicate equilibrium to maintain cellular homeostasis. Powerful biophysical
      techniques are needed to measure the localization and concentration of target
      molecules as well as to quantify complex molecular processes in model and in vivo
      systems. Two-photon microscopy and fluorescence correlation spectroscopy (FCS)
      can measure association and dynamics of appropriate molecules under equilibrium
      conditions. FCS provides information on motility (diffusion coefficients),
      concentration (number of particles), association (molecular brightness), and
      localization (image) of the target molecules. All of this information, in
      conjunction with computational modeling techniques, can help us to better
      understand the network of complex molecular interactions, which are at the basis
      of cellular processes. Fluorescence imaging techniques add the beauty of
      visualization to the scientific information. Photons emitted by a fluorescent dye
      are digitized, and the associated spatial information and intensity can be
      translated into different colors and shades providing the researcher not only
      with quantitative intensity information but also with spatial resolution and
      visual comprehension of two- or three-dimensional images. In this Account, we
      review the use of two-photon excitation microscopy and FCS in the study of lipid
      protein interactions. We discuss these new methodologies and techniques, and we
      present examples of different complexity from qualitative to quantitative, from
      simple model systems to studies in living cells.

PMID- 15966714
TI  - Polar attributes of supercritical carbon dioxide.
AB  - Supercritical carbon dioxide (scCO(2)) is increasingly promoted as an
      environmentally benign alternative to conventional organic solvents. The
      supercritical state bridges the gap between liquid and gaseous states by offering
      gaslike diffusion rates and liquidlike solvent densities, thereby enabling
      potential opportunities as a reaction and separation medium in chemical industry.
      Understanding the solvent behavior of liquid and scCO(2) is of critical
      importance to enable the design of CO(2)-philic molecular systems and to expand
      the use of these solvent systems to a wider range of chemical processes.
      Historically CO(2) was treated as a nonpolar solvent, primarily because of its
      low dielectric constant and zero molecular dipole moment. CO(2) has also been
      described as a quadrupolar solvent because of its significant quadrupole moment.
      Recent studies suggest that, as far as the microscopic solvent behavior of CO(2)
      is concerned, CO(2) has the potential to act as both a weak Lewis acid and Lewis
      base. Also, strong theoretical and experimental evidence indicates that CO(2) can
      participate in conventional or nonconventional hydrogen-bonding interactions. All
      of these site-specific solute-solvent interactions are important to understand
      the fundamental nature of CO(2) as a solvent. In this Account, we discuss these
      polar attributes of CO(2) and their relation to solvation.

PMID- 15966715
TI  - Photocontrolling peptide alpha helices.
AB  - Reversible optical control of protein structure and function offers the
      possibility of probing and manipulating individual proteins within the complex
      environment of a living cell. As a first step toward creating artificial
      photocontrolled proteins, we have designed and synthesized reversible,
      photocontrolled peptide alpha helices. Here, I attempt to summarize the lessons
      learned from that endeavor.

PMID- 15966716
TI  - Strategies for constructing polymeric micelles and hollow spheres in solution via
      specific intermolecular interactions.
AB  - We succeeded recently in developing a series of new pathways to polymeric
      micelles and hollow spheres via intermolecular specific interactions. A new
      micellization mechanism of block copolymers was realized by using the specific
      interaction between a low molecular weight compound and one of the blocks in low
      polarity solvents. Many more successes have been achieved by our "block copolymer
      free" strategies. We are now able to use homopolymers, random copolymers,
      oligomers, etc. as building blocks to construct noncovalently connected micelles
      (NCCM), in which the core and shell are connected by hydrogen bonding. Some of
      such NCCMs are readily converted further into hollow spheres by cross-linking the
      shell and then switching the medium to one that dissolves the core. Rigid polymer
      chains and their complementary homopolymers can directly assemble into large
      hollow spheres thanks to the propensity to parallel packing of the rigid chains.
      In addition, some of the NCCMs show perfect stimuli-responsive properties. pH
      dependent micellization and pH-dependent micelle-hollow-sphere transition are
      realized in water-soluble graft copolymers driven by complexation and
      decomplexation between the main chain and grafts.

PMID- 15966717
TI  - The internal cavity of the staphylococcal alpha-hemolysin pore accommodates
      approximately 175 exogenous amino acid residues.
AB  - The cavity within the cap domain of the transmembrane staphylococcal alpha
      hemolysin (alphaHL) pore is roughly a sphere of diameter approximately 45 A
      (molecular surface volume approximately 39,500 A(3)). We tested the ability of
      the cavity to accommodate exogenous polypeptide chains. Concatemerized Gly/Ser
      containing sequences ("loops", L; number of repeats = n; number of residues = 10n
      + 5, n = 0-21) were inserted at a position located within the cavity of the fully
      assembled heptameric alphaHL pore. Homomeric pores containing 25 or less residues
      in each loop (n <or= 2) could be assembled. The pores were protease-resistant,
      indicating that they had been formed correctly, and produced currents in planar
      lipid bilayers. The pores showed an up to 70% reduction in unitary conductance,
      depending on the length of the inserted loop. Protease-resistant heteromeric
      pores containing wild-type (W) and L subunits were also assembled: when n = 3, up
      to five L subunits were tolerated; when n = 4, three L subunits were tolerated;
      and when n = 5 or 6, two L subunits were tolerated. For n >or= 7, only one L
      subunit was incorporated. As the inserted loop was lengthened, transient closures
      were observed in planar bilayer experiments with single pores. However, L(1)W(6)
      pores with very long loops (n = 14 and 21) had unitary conductance values close
      to those of W(7), suggesting that the loop is extruded through the opening in the
      cap of the pore into the external medium. Further analysis of bilayer recordings
      and electrophoretic migration patterns indicates that the upper capacity of the
      cavity is approximately 175 amino acids. The findings suggest that small
      functional peptides or proteins might be assembled within the alphaHL pore.

PMID- 15966718
TI  - The crystal structure of Escherichia coli ketopantoate reductase with NADP+
      bound.
AB  - The NADPH-dependent reduction of ketopantoate to pantoate, catalyzed by
      ketopantoate reductase (KPR; EC 1.1.1.169), is essential for the biosynthesis of
      pantothenate (vitamin B(5)). Here we present the crystal structure of Escherichia
      coli KPR with NADP(+) bound, solved to 2.1 A resolution. The cofactor is bound in
      the active site cleft between the N-terminal Rossmann-fold domain and the C
      terminal alpha-helical domain. The thermodynamics of cofactor and substrate
      binding were characterized by isothermal titration calorimetry. The dissociation
      constant for NADP(+) was found to be 6.5 muM, 20-fold larger than that for NADPH
      (0.34 muM). The difference is primarily due to the entropic term, suggesting
      favorable hydrophobic interactions of the more lipophilic nicotinamide ring in
      NADPH. Comparison of this binary complex structure with the previously studied
      apoenzyme reveals no evidence for large domain movements on cofactor binding.
      This observation is further supported both by molecular dynamics and by
      calorimetric analysis. A model of the ternary complex, based on the structure
      presented here, provides novel insights into the molecular mechanism of enzyme
      catalysis. We propose a conformational switch of the essential Lys176 from the
      "resting" state observed in our structure to an "active" state, to bind
      ketopantoate. Additionally, we identify the importance of Asn98 for substrate
      binding and enzyme catalysis.

PMID- 15966719
TI  - Slow solvation dynamics at the active site of an enzyme: implications for
      catalysis.
AB  - Solvation dynamics at the active site of an enzyme, glutaminyl-tRNA synthetase
      (GlnRS), was studied using a fluorescence probe, acrylodan, site-specifically
      attached at cysteine residue C229, near the active site. The picosecond time
      dependent fluorescence Stokes shift indicates slow solvation dynamics at the
      active site of the enzyme, in the absence of any substrate. The solvation
      dynamics becomes still slower when the substrate (glutamine or tRNA(Gln)) binds
      to the enzyme. A mutant Y211H-GlnRS was constructed in which the glutamine
      binding site is disrupted. The mutant Y211H-GlnRS labeled at C229 with acrylodan
      exhibited significantly different solvent relaxation, thus demonstrating that the
      slow dynamics is indeed associated with the active site. Implications for
      catalysis and specificity have been discussed.

PMID- 15966720
TI  - Ethanol-perturbed amyloidogenic self-assembly of insulin: looking for origins of
      amyloid strains.
AB  - A model cosolvent, ethanol, has profound and diversified effects on the
      amyloidogenic self-assembly of insulin, yielding spectroscopically and
      morphologically distinguishable forms of beta-aggregates. The alcohol reduces
      hydrodynamic radii of insulin molecules, decreases enthalpic costs associated
      with aggregation-prone intermediate states, and accelerates the aggregation
      itself. Increasing the concentration of the cosolvent promotes curved, amorphous,
      and finally donut-shaped forms. According to FT-IR data, inter-beta-strand
      hydrogen bonding is stronger in fibrils formed in the presence of ethanol.
      Mechanisms underlying the polymorphism of insulin aggregates were investigated by
      spectroscopic (CD, FT-IR, and fluorescence anisotropy) and calorimetric (DSC and
      PPC) methods. The nonmonotonic character of the influence of ethanol on insulin
      aggregation suggests that both preferential exclusion (predominant at the low
      concentrations) and direct alcohol-protein interactions are involved. The
      perturbed hydration of aggregation nuclei appears to be a decisive factor in
      selection of a dominant mode of beta-strand alignment. It may override
      unfavorable structural consequences of an alternative strand-to-strand stacking,
      such as strained hydrogen bonding. A hypothetical mechanism of inducing different
      amyloid "strains" has been put forward. The cooperative character of fibril
      assembly creates enormous energy barriers for any interstrain transition, which
      renders the energy landscape comblike-shaped.

PMID- 15966722
TI  - Structural and functional characterization of Mycobacterium tuberculosis CmtR, a
      PbII/CdII-sensing SmtB/ArsR metalloregulatory repressor.
AB  - The SmtB/ArsR family of prokaryotic metalloregulators are winged-helix
      transcriptional repressors that collectively provide resistance to a wide range
      of both biologically required and toxic heavy-metal ions. CmtR is a recently
      described Cd(II)/Pb(II) regulator expressed in Mycobacterium tuberculosis that is
      structurally distinct from the well-characterized SmtB/ArsR Cd(II)/Pb(II) sensor,
      Staphylococcus aureus plasmid pI258-encoded CadC. From functional analyses and a
      multiple sequence alignment of CmtR paralogs, M. tuberculosis CmtR is proposed to
      bind Pb(II) and Cd(II) via coordination by Cys57, Cys61, and Cys102 [Cavet et al.
      (2003) J. Biol. Chem. 278, 44560-44566]. We establish here that both wild-type
      and C102S CmtR are homodimers and bind Cd(II) and Pb(II) via formation of
      cysteine thiolate-rich coordination bonds. UV-vis optical spectroscopy, (113)Cd
      NMR spectroscopy (delta = 480 ppm), and (111m)Cd perturbed angular correlation
      (PAC) spectroscopy suggest two or three thiolate donors in the wild-type protein.
      Cys57 and Cys61 anchor the coordination complex, while Cys102 plays only an
      accessory role in stabilizing the metal chelate in the free protein because C102S
      CmtR binds Cd(II) and Zn(II) with only approximately 10-20-fold lower affinity
      relative to wild-type CmtR but approximately 100-1000-fold lower for Pb(II).
      Quantitative investigation of CmtR-cmt O/P binding equilibria using fluorescence
      anisotropy, however, reveals that Cys102 functions as a key allosteric metal
      ligand, because substitution of Cys102 abrogates disassembly of oligomeric CmtR
      cmt O/P oligomeric complexes. The implications of these findings on the evolution
      of distinct metal-sensing sites in a family of homologous proteins are discussed.

PMID- 15966721
TI  - Comparison of class A and D G protein-coupled receptors: common features in
      structure and activation.
AB  - All G protein-coupled receptors (GPCRs) share a common seven TM helix
      architecture and the ability to activate heterotrimeric G proteins. Nevertheless,
      these receptors have widely divergent sequences with no significant homology. We
      present a detailed structure-function comparison of the very divergent Class A
      and D receptors to address whether there is a common activation mechanism across
      the GPCR superfamily. The Class A and D receptors are represented by the
      vertebrate visual pigment rhodopsin and the yeast alpha-factor pheromone receptor
      Ste2, respectively. Conserved amino acids within each specific receptor class and
      amino acids where mutation alters receptor function were located in the
      structures of rhodopsin and Ste2 to assess whether there are functionally
      equivalent positions or regions within these receptors. We find several general
      similarities that are quite striking. First, strongly polar amino acids mediate
      helix interactions. Their mutation generally leads to loss of function or
      constitutive activity. Second, small and weakly polar amino acids facilitate
      tight helix packing. Third, proline is essential at similar positions in
      transmembrane helices 6 and 7 of both receptors. Mapping the specific location of
      the conserved amino acids and sites of constitutively active mutations identified
      conserved microdomains on transmembrane helices H3, H6, and H7, suggesting that
      there are underlying similarities in the mechanism of the widely divergent Class
      A and Class D receptors.

PMID- 15966723
TI  - Mutational, structural, and kinetic evidence for a dissociative mechanism in the
      GDP-mannose mannosyl hydrolase reaction.
AB  - GDP-mannose hydrolase (GDPMH) catalyzes the hydrolysis of GDP-alpha-d-sugars by
      nucleophilic substitution with inversion at the anomeric C1 atom of the sugar,
      with general base catalysis by H124. Three lines of evidence indicate a mechanism
      with dissociative character. First, in the 1.3 A X-ray structure of the GDPMH
      Mg(2+)-GDP.Tris(+) complex [Gabelli, S. B., et al. (2004) Structure 12, 927-935],
      the GDP leaving group interacts with five catalytic components: R37, Y103, R52,
      R65, and the essential Mg(2+). As determined by the effects of site-specific
      mutants on k(cat), these components contribute factors of 24-, 100-, 309-, 24-,
      and >/=10(5)-fold, respectively, to catalysis. Both R37 and Y103 bind the beta
      phosphate of GDP and are only 5.0 A apart. Accordingly, the R37Q/Y103F double
      mutant exhibits partially additive effects of the two single mutants on k(cat),
      indicating cooperativity of R37 and Y103 in promoting catalysis, and antagonistic
      effects on K(m). Second, the conserved residue, D22, is positioned to accept a
      hydrogen bond from the C2-OH group of the sugar undergoing substitution at C1, as
      was shown by modeling an alpha-d-mannosyl group into the sugar binding site. The
      D22A and D22N mutations decreased k(cat) by factors of 10(2.1) and 10(2.6),
      respectively, for the hydrolysis of GDP-alpha-d-mannose, and showed smaller
      effects on K(m), suggesting that the D22 anion stabilizes a cationic oxocarbenium
      transition state. Third, the fluorinated substrate, GDP-2F-alpha-d-mannose, for
      which a cationic oxocarbenium transition state would be destabilized by electron
      withdrawal, exhibited a 16-fold decrease in k(cat) and a smaller, 2.5-fold
      increase in K(m). The D22A and D22N mutations further decreased the k(cat) with
      GDP-2F-alpha-d-mannose to values similar to those found with GDP-alpha-d-mannose,
      and decreased the K(m) of the fluorinated substrate. The choice of histidine as
      the general base over glutamate, the preferred base in other Nudix enzymes, is
      not due to the greater basicity of histidine, since the pK(a) of E124 in the
      active complex (7.7) exceeded that of H124 (6.7), and the H124E mutation showed a
      10(2.2)-fold decrease in k(cat) and a 4.0-fold increase in K(m) at pH 9.3.
      Similarly, the catalytic triad detected in the X-ray structure (H124- - -Y127- - 
      P120) is unnecessary for orienting H124, since the Y127F mutation had only 2-fold
      effects on k(cat) and K(m) with either H124 or E124 as the general base. Hence, a
      neutral histidine rather than an anionic glutamate may be necessary to preserve
      electroneutrality in the active complex.

PMID- 15966724
TI  - Characterization of disulfide bonds in human nucleoside triphosphate
      diphosphohydrolase 3 (NTPDase3): implications for NTPDase structural modeling.
AB  - Cell-surface nucleotidases (NTPDases) contain 10 invariant cysteine residues in
      their extracellular regions. To investigate disulfide structure in human
      NTPDase3, we made single and double mutants of these 10 cysteines, and analyzed
      their enzymatic activity, glycosylation pattern, trafficking to the cell
      membrane, and sensitivity to reduction. The mutants constituted five distinct
      phenotypes, thus, strongly suggesting disulfide bonds between C92-C116 (first
      bond), C261-C308 (second bond), C289-C334 (third bond), C347-C353 (fourth bond),
      and C399-C422 (fifth bond). Due to conservation of the 10 cysteines, the
      identified five disulfide bonds are likely to exist in all cell-surface NTPDases.
      The third and fifth bonds are also present in the soluble NTPDases and are
      critical for processing, trafficking, and enzymatic activity. The fourth bond has
      minimal effect on processing and function, while the first and second bonds are
      of intermediate importance. Most of the N-linked glycosylation sites in the wild
      type enzyme are processed to complex oligosaccharides, but at least one site is
      high-mannose or hybrid in structure. Interestingly, disruption of the first
      disulfide bond resulted in some enzyme that lost sensitivity to endoglycosidase
      H, suggesting that the first disulfide bond in the wild-type enzyme shields some
      high-mannose glycans from terminal glycosylation. Comparative modeling by
      threading and homology modeling of the NTPDase3 sequence revealed a high degree
      of structural fold similarity with a bacterial exopolyphosphatase (PDB ). The
      resultant theoretical 3-D model of the extracellular portion of NTPDase3, based
      on homology with this exopolyphosphatase, is consistent with the assignment of
      the disulfide bonds occurring in regions of good fold similarity between NTPDase3
      and the exopolyphosphatase. The 3-D model obtained for NTPDase3 also suggests the
      structural basis for the importance of several apyrase conserved regions for the
      nucleotidase activities of the NTPDases.

PMID- 15966725
TI  - Perturbing the hydrophobic pocket of mandelate racemase to probe phenyl motion
      during catalysis.
AB  - Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg(2+)
      dependent 1,1-proton transfer that interconverts the enantiomers of mandelate.
      Crystal structures of MR reveal that the phenyl group of all ground-state ligands
      is located within a hydrophobic cavity, remote from the site of proton
      abstraction. MR forms numerous electrostatic and H-bonding interactions with the
      alpha-OH and carboxyl groups of the substrate, suggesting that these polar groups
      may remain relatively fixed in position during catalysis while the phenyl group
      is free to move between two binding sites [i.e., the R-pocket and the S-pocket
      for binding the phenyl group of (R)-mandelate and (S)-mandelate, respectively].
      We show that MR binds benzilate (K(i) = 0.67 +/- 0.12 mM) and (S)
      cyclohexylphenylglycolate (K(i) = 0.50 +/- 0.03 mM) as competitive inhibitors
      with affinities similar to that which the enzyme exhibits for the substrate.
      Therefore, the active site can simultaneously accommodate two phenyl groups,
      consistent with the existence of an R-pocket and an S-pocket. Wild-type MR
      exhibits a slightly higher affinity for (S)-mandelate [i.e., K(m)(S)(-)(man) <
      K(m)(R)(-)(man)] but catalyzes the turnover of (R)-mandelate slightly more
      rapidly (i.e., k(cat)(R)(-->)(S) > k(cat)(S)(-->)(R)). Upon introduction of
      steric bulk into the S-pocket using site-directed mutagenesis (i.e., the F52W,
      Y54W, and F52W/Y54W mutants), this catalytic preference is reversed. Although the
      catalytic efficiency (k(cat)/K(m)) of all the mutants was reduced (11-280-fold),
      all mutants exhibited a higher affinity for (R)-mandelate than for (S)-mandelate,
      and higher turnover numbers with (S)-mandelate as the substrate, relative to
      those with (R)-mandelate. (R)- and (S)-2-hydroxybutyrate are expected to be less
      sensitive to the additional steric bulk in the S-pocket. Unlike those for
      mandelate, the relative binding affinities for these substrate analogues are not
      reversed. These results are consistent with steric obstruction in the S-pocket
      and support the hypothesis that the phenyl group of the substrate may move
      between an R-pocket and an S-pocket during racemization. These conclusions were
      also supported by modeling of the binary complexes of the wild-type and F52W/Y54W
      enzymes with the substrate analogues (R)- and (S)-atrolactate, and of wild-type
      MR with bound benzilate using molecular dynamics simulations.

PMID- 15966726
TI  - Mutational and structural studies of the diisopropylfluorophosphatase from Loligo
      vulgaris shed new light on the catalytic mechanism of the enzyme.
AB  - The active site, the substrate binding site, and the metal binding sites of the
      diisopropylfluorophosphatase (DFPase) from Loligo vulgaris have been modified by
      means of site-directed mutagenesis to improve our understanding of the reaction
      mechanism. Enzymatic characterization of mutants located in the major groove of
      the substrate binding pocket indicates that large hydrophobic side chains at
      these positions are favorable for substrate turnover. Moreover, the active site
      residue His287 proved to be beneficial, but not essential, for DFP hydrolysis. In
      most cases, hydrophobic side chains at position 287 led to significant catalytic
      activities although reduced relative to the wild-type enzyme. With respect to the
      Ca-1 binding site, where catalysis occurs, various mutants indicated that the net
      charge at this calcium-binding site as well as the relative positions of the
      charged calcium ligands is crucial for catalytic activity. The importance of the
      electrostatic potential at the active site was furthermore revealed by various
      mutations of residues lining the interior of the central water-filled tunnel,
      which traverses the entire protein structure. In this respect, the structural
      features of residue His181, which is located at the opposite end of the DFPase
      tunnel relative to the active site, were characterized extensively. It was
      concluded that a tunnel-spanning hydrogen bond network, which includes a large
      number of apparently slow exchanging water molecules, relays any modifications in
      the electrostatics of the system to the active site, thus affecting the catalytic
      reactivity of the enzyme.

PMID- 15966727
TI  - Recovery of argininosuccinate lyase activity in duck delta1 crystallin.
AB  - Delta-crystallin, the major soluble protein component in the avian eye lens, is
      homologous to argininosuccinate lyase (ASL). Two delta-crystallin isoforms exist
      in ducks, delta1- and delta2-crystallin, which are 94% identical in amino acid
      sequence. While duck delta2-crystallin (ddeltac2) has maintained ASL activity,
      evolution has rendered duck delta1-crystallin (ddeltac1) enzymatically inactive.
      Previous attempts to regenerate ASL activity in ddeltac1 by mutating the residues
      in the 20s (residues 22-31) and 70s (residues 74-89) loops to those found in
      ddeltac2 resulted in a double loop mutant (DLM) which was enzymatically inactive
      (Tsai, M. et al. (2004) Biochemistry 43, 11672-82). This result suggested that
      one or more of the remaining five amino acid substitutions in domain 1 of the DLM
      contributes to the loss of ASL activity in ddeltac1. In the current study,
      residues Met-9, Val-14, Ala-41, Ile-43, and Glu-115 were targeted for
      mutagenesis, either alone or in combination, to the residues found in ddeltac2.
      ASL activity was recovered in the DLM by changing Met-9 to Trp, and this activity
      is further potentiated in the DLM-M9W mutant when Glu-115 is changed to Asp. The
      roles of Trp-9 and Asp-115 were further investigated by site-directed mutagenesis
      in wild-type ddeltac2. Changing the identity of either Trp-9 or Asp-115 in
      ddeltac2 resulted in a dramatic drop in enzymatic activity. The loss of activity
      in Trp-9 mutants indicates a preference for an aromatic residue at this position.
      Truncation mutants of ddeltac2 in which the first 8, 9, or 14 N-terminal residues
      were removed displayed either decreased or no ASL activity, suggesting residues 1
      14 are crucial for enzymatic activity in ddeltac2. Our kinetic studies combined
      with available structural data suggest that the N-terminal arm in ASL/delta2
      crystallin is involved in stabilizing regions of the protein involved in
      substrate binding and catalysis, and in completely sequestering the substrate
      from the solvent.

PMID- 15966729
TI  - The HIV-1 leader RNA conformational switch regulates RNA dimerization but does
      not regulate mRNA translation.
AB  - The untranslated leader RNA is the most conserved part of the human
      immunodeficiency virus type I (HIV-1) genome. It contains many regulatory motifs
      that mediate a variety of steps in the viral life cycle. Previous work showed
      that the full-length leader RNA can adopt two alternative structures: a long
      distance interaction (LDI) and a branched multiple-hairpin (BMH) structure. The
      BMH structure exposes the dimer initiation site (DIS) hairpin, whereas this motif
      is occluded in the LDI structure. Consequently, these structures differ in their
      capacity to form RNA dimers in vitro. The BMH structure is dimerization
      competent, due to DIS hairpin formation, but also presents the splice donor (SD)
      and RNA packaging (Psi) hairpins. In the LDI structure, an extended RNA packaging
      (Psi(E)) hairpin is folded, which includes the splice donor site and gag coding
      sequences. The gag initiation codon is engaged in a long distance base pairing
      interaction with sequences in the upstream U5 region in the BMH structure, thus
      forming the evolutionarily conserved U5-AUG duplex. Therefore, the LDI-BMH
      equilibrium may affect not only the process of RNA dimer formation but also
      translation initiation. In this study, we designed mutations in the 3'-terminal
      region of the leader RNA that alter the equilibrium of the LDI-BMH structures.
      The mutant leader RNAs are affected in RNA dimer formation, but not in their
      translation efficiency. These results indicate that the LDI-BMH status does not
      regulate HIV-1 RNA translation, despite the differential presentation of the gag
      initiation codon in both leader RNA structures.

PMID- 15966728
TI  - Probing the influence of stereoelectronic effects on the biophysical properties
      of oligonucleotides: comprehensive analysis of the RNA affinity, nuclease
      resistance, and crystal structure of ten 2'-O-ribonucleic acid modifications.
AB  - The syntheses of 10 new RNA 2'-O-modifications, their incorporation into
      oligonucleotides, and an evaluation of their properties such as RNA affinity and
      nuclease resistance relevant to antisense activity are presented. All
      modifications combined with the natural phosphate backbone lead to significant
      gains in terms of the stability of hybridization to RNA relative to the first
      generation DNA phosphorothioates (PS-DNA). The nuclease resistance afforded in
      particular by the 2'-O-modifications carrying a positive charge surpasses that of
      PS-DNA. However, small electronegative 2'-O-substituents, while enhancing the RNA
      affinity, do not sufficiently protect against degradation by nucleases.
      Similarly, oligonucleotides containing 3'-terminal residues modified with the
      relatively large 2'-O-[2-(benzyloxy)ethyl] substituent are rapidly degraded by
      exonucleases, proving wrong the assumption that steric bulk will generally
      improve protection against nuclease digestion. To analyze the factors that
      contribute to the enhanced RNA affinity and nuclease resistance we determined
      crystal structures of self-complementary A-form DNA decamer duplexes containing
      single 2'-O-modified thymidines per strand. Conformational preorganization of
      substituents, favorable electrostatic interactions between substituent and sugar
      phosphate backbone, and a stable water structure in the vicinity of the 2'-O
      modification all appear to contribute to the improved RNA affinity. Close
      association of positively charged substituents and phosphate groups was observed
      in the structures with modifications that protect most effectively against
      nucleases. The promising properties exhibited by some of the analyzed 2'-O
      modifications may warrant a more detailed evaluation of their potential for in
      vivo antisense applications. Chemical modification of RNA can also be expected to
      significantly improve the efficacy of small interfering RNAs (siRNA). Therefore,
      the 2'-O-modifications introduced here may benefit the development of RNAi
      therapeutics.

PMID- 15966730
TI  - Redox-dependent structural differences in putidaredoxin derived from homologous
      structure refinement via residual dipolar couplings.
AB  - Structural differences in the [2Fe-2S] ferredoxin, putidaredoxin (Pdx), from the
      camphor hydroxylation pathway of Pseudomonas putida have been investigated as a
      function of oxidation state of the iron cluster. Pdx is involved in biological
      electron transfer to cytochrome P450(cam) (CYP101). Redox-dependent differences
      have been observed previously for Pdx in terms of binding affinities to CYP101,
      NMR spectral differences, and dynamic properties. To further characterize these
      differences, structure refinement of both oxidized and reduced Pdx has been
      carried out using a hybrid approach utilizing paramagnetic distance restraints
      and NMR orientational restraints in the form of backbone (15)N residual dipolar
      couplings. Use of these new restraints has improved the structure of oxidized Pdx
      considerably over the earlier solution NMR structure without RDC restraints, with
      the new structure now much closer in overall fold to the recently published X-ray
      crystal structures. We now observe better defined relative orientations of the
      major secondary structure elements as also of the conformation of the metal
      binding loop region. Extension of this approach to structure calculation of
      reduced Pdx has identified structural differences that are primarily localized
      for residues in the C-terminal interaction domain consisting of the functionally
      important residue Trp 106 and regions near the metal binding loop in Pdx. These
      redox-dependent structural differences in Pdx correlate to dynamic changes
      observed before and may be linked to differences in binding and electron transfer
      properties between oxidized and reduced Pdx.

PMID- 15966731
TI  - Cys-10 mixed disulfide modifications exacerbate transthyretin familial variant
      amyloidogenicity: a likely explanation for variable clinical expression of
      amyloidosis and the lack of pathology in C10S/V30M transgenic mice?
AB  - The marked variation in clinical expression and age of familial amyloid disease
      onset is not well understood. One possibility is that metabolite modification(s)
      of a disease-associated mutant protein can change the energetics and propensity
      for misfolding, influencing the disease course. Each subunit of the transthyretin
      (TTR) tetramer has a single Cys residue that can exist in the SH form or as a
      mixed disulfide with the amino acid Cys or the peptide glutathione or fragments
      of the latter. The stability and amyloidogenicity of the clinically most
      important TTR variants (V30M and V122I) in their SH oxidation state were compared
      with those of their mixed disulfide adducts. All the Cys-10 mixed disulfide
      conjugates exhibited substantially decreased protein stability (urea, pH 7) and a
      higher rate and extent of amyloidogenesis (slightly acidic conditions). We also
      investigated the amyloidogenicity and stability of a C10S/V30M TTR double mutant
      which lacks the ability to make mixed disulfides, but retains the disease
      associated V30M mutation. Unlike V30M TTR, this double mutant is nonamyloidogenic
      in transgenic mice. Our in vitro data reveal that the C10S/V30M and V30M TTR
      homotetramers have identical amyloidogenicity and stability, implying that Cys-10
      mixed disulfide formation enhances amyloidogenesis in V30M transgenic mice. Given
      the high proportion of TTR subunits having mixed disulfide modifications in human
      plasma ( approximately 50%), and the data within demonstrating their increased
      amyloidogenicity, we submit that disulfide metabolite modifications have the
      potential to influence the course of amyloidoses, including TTR amyloidoses
      caused by mutations.

PMID- 15966732
TI  - Solution structure of the sulfite reductase flavodoxin-like domain from
      Escherichia coli.
AB  - The flavoprotein moiety of Escherichia coli sulfite reductase (SiR-FP) is
      homologous to electron transfer proteins such as cytochrome-P450 reductase (CPR)
      or nitric oxide synthase (NOS). We report on the three-dimensional structure of
      SiR-FP18, the flavodoxin-like domain of SiR-FP, which has been determined by NMR.
      In the holoenzyme, this domain plays an important role by shuttling electrons
      from the FAD to the hemoprotein (the beta-subunit). The structure presented here
      was determined using distance and torsion angle information in combination with
      residual dipolar couplings determined in two different alignment media. Several
      protein-FMN NOEs allowed us to place the prosthetic group in its binding pocket.
      The structure is well-resolved, and (15)N relaxation data indicate that SiR-FP18
      is a compact domain. The binding interface with cytochrome c, a nonphysiological
      electron acceptor, has been determined using chemical shift mapping. Comparison
      of the SiR-FP18 structure with the corresponding domains from CPR and NOS shows
      that the fold of the protein core is highly conserved, but the analysis of the
      electrostatic surfaces reveals significant differences between the three domains.
      These observations are placed in the physiological context so they can contribute
      to the understanding of the electron transfer mechanism in the SiR holoenzyme.

PMID- 15966733
TI  - Forcing nonamyloidogenic beta-synuclein to fibrillate.
AB  - The fibrillation and aggregation of alpha-synuclein is a key process in the
      formation of intracellular inclusions, Lewy bodies, in substantia nigral neurons
      and, potentially, in the pathology of Parkinson's disease and several other
      neurodegenerative disorders. Alpha-synuclein and its homologue beta-synuclein are
      both natively unfolded proteins that colocalize in presynaptic terminals of
      neurons in many regions of the brain, including those of dopamine-producing cells
      of the substantia nigra. Unlike its homologue, beta-synuclein does not form
      fibrils and has been shown to inhibit the fibrillation of alpha-synuclein. In
      this study, we demonstrate that fast and efficient aggregation and fibrillation
      of beta-synuclein can be induced in the presence of a variety of factors. Certain
      metals (Zn(2+), Pb(2+), and Cu(2+)) induce a partially folded conformation of
      beta-synuclein that triggers rapid fibrillation. In the presence of these metals,
      mixtures of alpha- and beta-synucleins exhibited rapid fibrillation. The metal
      induced fibrillation of beta-synuclein was further accelerated by the addition of
      glycosaminoglycans or high concentrations of macromolecular crowding agents. Beta
      synuclein also rapidly formed soluble oligomers and fibrils in the presence of
      pesticides, whereas the addition of low concentrations of organic solvents
      induced formation of amorphous aggregates. These new findings demonstrate the
      potential effect of environmental pollutants in generating an amyloidogenic, and
      potentially neurotoxic, conformation, in an otherwise benign protein.

PMID- 15966734
TI  - Oxidation of low-density lipoproteins induces amyloid-like structures that are
      recognized by macrophages.
AB  - The macrophage scavenger receptor CD36 plays a key role in the initiation of
      atherosclerosis through its ability to bind to and internalize oxidized low
      density lipoproteins (oxLDL). Prompted by recent findings that the CD36 receptor
      also recognizes amyloid fibrils formed by beta-amyloid and apolipoprotein C-II,
      we investigated whether the oxidation of low-density lipoproteins (LDL) generates
      characteristic amyloid-like structures and whether these structures serve as CD36
      ligands. Our studies demonstrate that LDL oxidized by copper ions, 2,2-azobis(2
      amidinopropane) dihydrochloride (AAPH), or ozone react with the diagnostic
      amyloid dyes thioflavin T and Congo Red and bind to serum amyloid P component
      (SAP), a universal constituent of physiological amyloid deposits. X-ray powder
      diffraction patterns for native LDL show a diffuse powder diffraction ring with
      maximum intensity corresponding to an atomic spacing of approximately 4.7 A,
      consistent with the spacing between beta-strands in a beta-sheet. Ozone treatment
      of LDL generates an additional diffuse powder diffraction ring with maximum
      intensity indicating a spacing of approximately 9.8 A. This distance is
      consistent with the presence of cross-beta-structure, a defining characteristic
      of amyloid. Evidence that these cross-beta-amyloid structures in oxLDL are
      recognized by macrophages is provided by the observation that SAP strongly
      inhibits the association and internalization of (125)I-labeled copper-oxidized
      LDL by peritoneal macrophages. The ability of SAP to bind to amyloid-like
      structures in oxLDL and prevent lipid uptake by macrophages highlights the
      potential importance of these structures and suggests an important preventative
      role for SAP in foam cell formation and early-stage atherosclerosis.

PMID- 15966735
TI  - Structure and mechanism of action of an inverting mutant sialidase.
AB  - Mutagenesis of the conserved tyrosine (Y370) of the Micromonospora viridifaciens
      sialidase to small amino acids changes the mechanism of catalysis from retention
      of anomeric configuration to inversion [Watson, J. N., et al. (2003) Biochemistry
      42, 12682-12690]. For the Y370G mutant enzyme-catalyzed hydrolysis of a series of
      aryl sialosides and 3'-sialyllactose, the derived Bronsted parameters (beta(lg))
      on k(cat) and k(cat)/K(m) are -0.63 +/- 0.05 and -0.80 +/- 0.08, respectively.
      Thus, for the Y370G enzyme, glycosidic C-O bond cleavage is rate-determining.
      Analysis of the activity of the Y370G mutant and wild-type enzymes against a
      substrate [3,4-dihydro-2H-pyrano[3,2-c]pyridinium alpha-d-N-acetylneuraminide
      (DHP-alphaNeu5Ac)] whose hydrolysis cannot be accelerated by acid catalysis is
      consistent with these reactions proceeding via S(N)1 and S(N)2 mechanisms,
      respectively. The overall structure of the Y370G mutant sialidase active site is
      very similar to the previously reported wild-type structure [Gaskell, A., et al.
      (1995) Structure 3, 1197-1205], although removal of the tyrosine residue creates
      two significant changes to the active site. First, the anomeric oxygen atom of
      the hydrolysis product (beta-N-acetylneuraminic acid) and four water molecules
      bind in the large cavity created by the Y370G mutation. Second, the side chain of
      Asn310 moves to make a strong hydrogen bond to one of the bound water molecules.

PMID- 15966736
TI  - Interaction of C-terminal loop 13 of sodium-glucose cotransporter SGLT1 with
      lipid bilayers.
AB  - We have previously shown that C-terminal loop 13 of SGLT1 acts as a major binding
      domain for the aglucon residues of d-glucose transport inhibitors, phlorizin
      (Raja, M. M., Tyagi, N. K., and Kinne, R. K. H. (2003) Phlorizin Recognition in a
      C-terminal Fragment of SGLT1 Studied by Tryptophan Scanning and Affinity
      Labeling, J. Biol. Chem. 278, 49154-49163) and alkyl glucosides (Raja, M. M.,
      Kipp, H., and Kinne, R. K. H. (2004) C-Terminus Loop 13 of Na(+) Glucose
      Cotransporter SGLT1 Contains a Binding Site for Alkyl Glucosides, Biochemistry
      43, 10944-10951). Topology of this loop with regard to the membrane lipids is
      hitherto a point of debate. Here we report on in vitro incorporation studies
      using fluorescence of Trp mutants of loop 13 to determine the position of various
      parts of the loop with the lipid bilayer. Six single Trp mutants were prepared as
      described in previous studies (Raja et al., 2003) and subsequently incorporated
      into DOPC:DOPG (60:40% molar ratio) lipid vesicles. Upon addition of the
      phospholipids only one mutant, R601W, exhibited no change in the fluorescence
      intensities, position of maxima, or acrylamide accessibility. Mutants Q581W,
      E621W, and L630W exhibited the most pronounced blue shifts (3-6 nm) and
      protection against acrylamide, suggesting a position of these segments within the
      lipid bilayer. This assumption was confirmed by the result that the fluorescence
      of only these mutants was quenched by doxyl spin membrane embedded labels in the
      5- or 12-positions of the acyl side chain of phospholipids. The other parts of
      the peptide appear to remain outside of the lipid vesicles. Trp-591 and Trp-611
      showed, although to a different extent, increase in fluorescence, blue shift of
      maxima, and decrease in acrylamide accessibility but no interaction with the spin
      labeled phospholipids. This suggests changes in the conformation of the peptide
      itself. These conformation changes are probably induced by the interaction of an
      adjacent lysine rich region of the peptide with the negatively charged DOPG,
      since in the absence of this lipid no incorporation of loop 13 into the bilayer
      is observed. Trypsin cleavage experiments of loop 13 in proteoliposomes yield a
      peptide containing amino acid residues 603 to 614, confirming that this part of
      the loop is accessible at the extravesicular face of the membranes. The studies
      show that at least in the in vitro system the part of loop 13 essential for the
      interaction with the transport inhibitors is located extracellularly, making a
      similar arrangement in the intact SGLT1 probable.

PMID- 15966738
TI  - The loop C region of the murine 5-HT3A receptor contributes to the differential
      actions of 5-hydroxytryptamine and m-chlorophenylbiguanide.
AB  - Sequence and predicted structural similarities between members of the Cys loop
      superfamily of ligand-gated ion channel receptors and the acetylcholine binding
      protein (AChBP) suggest that the ligand-binding site is formed by six loops that
      intersect at subunit interfaces. We employed site-directed mutagenesis to
      investigate the role of amino acids from the loop C region of the murine 5
      HT(3AS)R in interacting with two structurally different agonists, serotonin (5
      HT) and m-chlorophenylbiguanide (mCPBG). Mutant receptors were evaluated using
      radioligand binding, two-electrode voltage clamp, and immunofluorescence studies.
      Electrophysiological assays were employed to identify changes in response
      characteristics and relative efficacies of mCPBG and the partial agonist, 2
      methyl 5-HT (2-Me5-HT). We have also constructed novel 5-HT and mCPBG docked
      models of the receptor binding site based on homology models of the AChBP. Both
      ligand-docked models correlate well with results from mutagenesis and
      electrophysiological assays. Four key amino acids were identified as being
      important to ligand binding and/or gating of the receptor. Among these, I228 and
      D229 are specific for effects mediated by 5-HT compared to mCPBG, indicating a
      differential interaction of these ligands with loop C. Residues F226 and Y234 are
      important for both 5-HT and mCPBG interactions. Mutations at F226, I228, and Y234
      also altered the relative efficacies of agonists, suggesting a role in the gating
      mechanism.

PMID- 15966739
TI  - Precursors of novel Gla-containing conotoxins contain a carboxy-terminal
      recognition site that directs gamma-carboxylation.
AB  - Vitamin K-dependent gamma-glutamyl carboxylase catalyzes the conversion of
      glutamyl residues to gamma-carboxyglutamate. Its substrates include vertebrate
      proteins involved in blood coagulation, bone mineralization, and signal
      transduction and invertebrate ion channel blockers known as conotoxins. Substrate
      recognition involves a recognition element, the gamma-carboxylation recognition
      site, typically located within a cleavable propeptide preceding the targeted
      glutamyl residues. We have purified two novel gamma-carboxyglutamate-containing
      conotoxins, Gla-TxX and Gla-TxXI, from the venom of Conus textile. Their cDNA
      deduced precursors have a signal peptide but no apparent propeptide. Instead,
      they contain a C-terminal extension that directs gamma-carboxylation but is not
      found on the mature conotoxin. A synthetic 13-residue "postpeptide" from the Gla
      TxXI precursor reduced the K(m) for the reaction of the Conus gamma-carboxylase
      with peptide substrates, including FLEEL and conantokin-G, by up to 440-fold,
      regardless of whether it was positioned at the N- or C-terminal end of the mature
      toxin. Comparison of the postpeptides to propeptides from other conotoxins
      suggested some common elements, and amino acid substitutions of these residues
      perturbed gamma-carboxylation of the Gla-TxXI peptide. The demonstration of a
      functional and transferable C-terminal postpeptide in these conotoxins indicates
      the presence of the gamma-carboxylation recognition site within the postpeptide
      and defines a novel precursor structure for vitamin K-dependent polypeptides. It
      also provides the first formal evidence to prove that gamma-carboxylation occurs
      as a post-translational rather than a cotranslational process.

PMID- 15966737
TI  - Characterization of a bifunctional PutA homologue from Bradyrhizobium japonicum
      and identification of an active site residue that modulates proline reduction of
      the flavin adenine dinucleotide cofactor.
AB  - PutA is a bifunctional flavoenzyme in bacteria that catalyzes the four-electron
      oxidation of proline to glutamate. In certain prokaryotes such as Escherichia
      coli, PutA is also a transcriptional repressor of the proline utilization (put)
      genes and thus is trifunctional. In this work, we have begun to assess
      differences between bifunctional and trifunctional PutA enzymes by examining the
      PutA protein from Bradyrhizobium japonicum (BjPutA). Primary structure analysis
      of BjPutA shows it lacks the DNA-binding domain of E. coli PutA (EcPutA).
      Consistent with this prediction, purified BjPutA does not exhibit DNA-binding
      activity in native gel mobility shift assays with promoter regions of the putA
      gene from B. japonicum. The catalytic and redox properties of BjPutA were
      characterized and a reduction potential (E(m)) value of -0.132 V (pH 7.5) was
      determined for the bound FAD/FADH(2) couple in BjPutA that is significantly more
      negative ( approximately 55 mV) than the E(m) for EcPutA-bound FAD. The more
      negative E(m) value thermodynamically limits proline reduction of the FAD
      cofactor in BjPutA. In the presence of phospholipids, reduction of BjPutA is
      stimulated, suggesting lipids influence the FAD redox environment. Accordingly,
      an E(m) value of -0.114 V (pH 7.5) was determined for BjPutA-bound FAD in the
      presence of polar lipids. The molecular basis for the lower reduction potential
      of FAD in BjPutA relative to EcPutA was explored by site-directed mutagenesis.
      Amino acid sequence alignment between BjPutA and EcPutA indicates only one
      difference in active site residues near the isoalloxazine ring of FAD: Val402 in
      EcPutA is substituted at the analogous position in BjPutA with Ala310.
      Replacement of A310 by Val in the BjPutA mutant A310V raised the reduction
      potential of bound FAD relative to wild-type BjPutA to an E(m) value of -0.09 V
      (pH 7.5). The >40-mV positive shift in the potential of the BjPutA mutant A310V
      suggests that the corresponding Val residue in EcPutA helps poise the FAD redox
      potential for thermodynamically favored proline reduction thereby allowing EcPutA
      to be efficiently regulated by proline availability. Limited proteolysis of
      BjPutA under reducing conditions shows FAD reduction does not influence BjPutA
      conformation indicating further that the redox dependent regulation observed with
      EcPutA may be limited to trifunctional PutA homologues.

PMID- 15966740
TI  - Controlled reduction of the humidity induces a shortcut recovery reaction in the
      photocycle of photoactive yellow protein.
AB  - The photocycle of the blue-light photoreceptor protein Photoactive Yellow Protein
      (PYP) was studied at reduced relative humidity (RH). Photocycle kinetics and
      spectra were measured in thin films of PYP in which the relative humidity was set
      at values between 29 and 98% RH with saturated solutions of various salts. We
      show that in this range, approximately 200 water molecules per PYP molecule are
      released from the film. As humidity decreased, photocycle transition rates
      changed, until at low humidity (RH < 50%) an authentic photocycle was no longer
      observed and the absorption spectrum of the dark, equilibrium state of PYP
      started to shift to 355 nm, that is, to a form resembling that of pB(dark). At
      moderately reduced humidity (i.e., >50% RH), an authentic photocycle is still
      observed, although its characteristics differ from those in solution. As humidity
      decreases, the rate of ground state recovery increases, while the rate of
      depletion of the first red-shifted intermediate pR dramatically decreases. The
      latter observation contrasts all so-far known modulations of the rate of the
      transition of the red-shifted- to the blue-shifted intermediates of PYP, which is
      consistently accelerated by all other modulations of the mesoscopic context of
      the protein. Under these same conditions, the long-lived, blue-shifted
      intermediate was formed not only with slower kinetics than in solution but also
      to a smaller extent. Global analysis of these data indicates that in this low
      humidity environment the photocycle can take a different route than in solution,
      that is, part of pG recovers directly from pR. These experiments on wild-type
      PYP, in combination with observations on a variant of PYP obtained by site
      directed mutagenesis (the E46Q mutant protein), further document the context
      dependence of the photocycle transitions of PYP and are relevant for the
      interpretation of results obtained in both spectroscopic and diffraction studies
      with crystalline PYP.

PMID- 15966742
TI  - Genetic polymorphism and expression of a highly potent scorpion depressant toxin
      enable refinement of the effects on insect Na channels and illuminate the key
      role of Asn-58.
AB  - We isolated from the venom of the scorpion Leiurus quinquestriatus hebraeus an
      extremely active anti-insect selective depressant toxin, Lqh-dprIT(3). Cloning of
      Lqh-dprIT(3) revealed a gene family encoding eight putative polypeptide variants
      (a-h) differing at three positions (37A/G, 50D/E, and 58N/D). All eight toxin
      variants were expressed in a functional form, and their toxicity to blowfly
      larvae, binding affinity for cockroach neuronal membranes, and CD spectra were
      compared. This analysis links Asn-58, which appears in variants a-d, to a toxin
      conformation associated with high binding affinity for insect sodium channels.
      Variants e-h, bearing Asp-58, exhibit a different conformation and are less
      potent. The importance of Asn-58, which is conserved in other depressant toxins,
      was further validated by construction and analysis of an N58D mutant of the well
      characterized depressant toxin, LqhIT(2). Current and voltage clamp assays using
      the cockroach giant axon have shown that despite the vast difference in potency,
      the two types of Lqh-dprIT(3) variants (represented by Lqh-dprIT(3)-a and Lqh
      dprIT(3)-e) are capable of blocking the action potentials (manifested as flaccid
      paralysis in blowfly larvae) and shift the voltage dependence of activation to
      more negative values, which typify the action of beta-toxins. Moreover, the
      stronger and faster shift in voltage dependence of activation and lack of tail
      currents observed in the presence of Lqh-dprIT(3)-a suggest an extremely
      efficient trapping of the voltage sensor compared to that of Lqh-dprIT(3)-e. The
      current clamp assays revealed that repetitive firing of the axon, which is
      reflected in contraction paralysis of blowfly larvae, can be obtained with either
      the less potent Lqh-dprIT(3)-e or the highly potent Lqh-dprIT(3)-a at more
      negative membrane potentials. Thus, the contraction symptoms in flies are likely
      to be dominated by the resting potential of neuronal membranes. This study
      clarifies the electrophysiological basis of the complex symptoms induced by
      scorpion depressant toxins in insects, and highlights for the first time
      molecular features involved in their activity.

PMID- 15966741
TI  - Ligand modulation of lateral segregation of a G-protein-coupled receptor into
      lipid microdomains in sphingomyelin/phosphatidylcholine solid-supported bilayers.
AB  - A growing body of evidence supports the idea that the plasma membrane bilayer is
      characterized by a laterally inhomogeneous mixture of lipids, having an organized
      structure in which lipid molecules segregate into small domains or patches. Such
      microdomains are characterized by high contents of sphingolipids that form
      thicker liquid-ordered regions that are resistant to extraction with nonionic
      detergents. The existence of lipid lateral segregation has been demonstrated in
      both model and biological membranes, although its role in protein sorting and
      membrane function still remains unclear. In these studies, plasmon-waveguide
      resonance (PWR) spectroscopy was employed to investigate the properties of
      microdomains in a model system consisting of a solid-supported lipid bilayer
      composed of a 1:1 mixture of palmitoyloleoylphosphatidylcholine (POPC) and brain
      sphingomyelin (SM), and their influence on the partitioning and functioning of
      the human delta opioid receptor (hDOR), a G-protein coupled receptor (GPCR).
      Resonance signals corresponding to two microdomains (POPC-rich and SM-rich) were
      observed in such bilayers, and the sorting of the receptor into each domain was
      highly dependent on the type of ligand that was bound. When no ligand was bound,
      the receptor was incorporated preferentially into the POPC-rich domain; when an
      agonist or antagonist was bound, the receptor was incorporated preferentially
      into the SM-rich component, although with a 2-fold greater propensity for this
      microdomain in the case of the agonist. Binding of G-protein to the agonist-bound
      receptor in the SM-rich domain occurred with a 30-fold higher affinity than
      binding to the receptor in the PC-rich domain. The binding of the agonist to an
      unliganded receptor in the bilayer produced receptor trafficking from the PC-rich
      to the SM-rich component. Since the SM-rich domain is thicker than the PC-rich
      domain, and previous studies with the hDOR have shown that the receptor is
      elongated upon agonist activation, we propose that hydrophobic matching between
      the receptor and the lipid is a driving force for receptor trafficking to the SM
      rich component.

PMID- 15966743
TI  - Involvement of nonlamellar-prone lipids in the stability increase of human
      cytochrome P450 1A2 in reconstituted membranes.
AB  - The effect of nonlamellar-prone lipids, diacylglycerol (DG) and
      phosphatidylethanolamine (PE), on the stability of human cytochrome P450 1A2
      (CYP1A2) was examined. When 100% phosphatidylcholine (PC) in standard vesicles
      was gradually replaced with either DG or PE, the stability of CYP1A2 increased;
      the incubation time-dependent destruction of spectrally detectable P450, decrease
      of catalytic activity, reduction of intrinsic fluorescence, and increased
      sensitivity to trypsin digestion were significantly alleviated. The ternary
      system of PC/PE/DG increased the stability of CYP1A2 more, even at lower
      concentrations of each nonlamellar-prone lipid, than that of the binary lipid
      mixture (PC/nonlamellar lipid). By incorporating the nonlamellar-prone lipids,
      the CYP1A2-induced increase of the surface pressure of the lipid monolayer was
      much higher compared to that for 100% PC. Increased surface pressure indicates a
      deep insertion of the protein into lipid monolayers. Nonlamellar lipids also
      increased the transition temperature of CYP1A2 in thermal unfolding and reduced
      the incubation time-dependent detachment of membrane-bound CYP1A2 from vesicles.
      Taken together, these results suggest that nonlamellar lipids per se and/or the
      phase properties of the membrane containing these lipids are important in the
      enhanced stability of CYP1A2 and the concomitant maintenance of catalytic
      activity of the protein.

PMID- 15966744
TI  - A truncated Fibrobacter succinogenes 1,3-1,4-beta-d-glucanase with improved
      enzymatic activity and thermotolerance.
AB  - As an approach to improving Fibrobacter succinogenes 1,3-1,4-beta-d-glucanase
      (Fsbeta-glucanase) for use in industry and to studying the structure-function
      relationship of the C-terminus in the enzyme, a C-terminally truncated (
      approximately 10 kDa) Fsbeta-glucanase was generated using a PCR-based gene
      truncation method and then overexpressed in either Escherichia coli BL21(DE3) or
      Pichia pastoris strain X-33 host cells. The initial rate kinetics, protein
      folding, and thermostability of the wild-type and truncated glucanases were
      characterized. The truncated enzyme expressed in Pichia cells was found to be
      glycosylated and composed of two dominant polypeptide bands as judged by SDS
      PAGE. An approximate 3-4-fold increase in the turnover rate (k(cat)), relative to
      that of the full-length enzyme, was detected for the purified truncated
      glucanases produced in E. coli (designated TF-glucanase) or Pichia host cells
      (designated glycosylated TF-glucanase). The glycosylated TF-glucanase is the most
      active known 1,3-1,4-beta-d-glucanase, with a specific activity of 10 800 +/- 200
      units/mg. Similar binding affinities for lichenan (K(m) = 2.5-2.89 mg/mL) were
      detected for the full-length enzyme, TF-glucanase, and glycosylated TF-glucanase.
      Both forms of truncated glucanase retained more than 80% of their original
      enzymatic activity after a 10 min incubation at 90 degrees C, whereas the full
      length enzyme possessed only 30% of its original enzymatic activity after the
      same treatment. This report demonstrates that deletion of the C-terminal region (
      approximately 10 kDa) in Fsbeta-glucanase, consisting of serine-rich repeats and
      a basic terminal domain rich in positively charged amino acids, significantly
      increases the catalytic efficiency and thermotolerance of the enzyme.

PMID- 15966745
TI  - Rational transformation of Lactobacillus reuteri 121 reuteransucrase into a
      dextransucrase.
AB  - Glucansucrase or glucosyltransferase (GTF) enzymes of lactic acid bacteria
      display high sequence similarity but catalyze synthesis of different alpha
      glucans (e.g., dextran, mutan, alternan, and reuteran) from sucrose. The
      variations in glucosidic linkage specificity observed in products of different
      glucansucrase enzymes appear to be based on relatively small differences in amino
      acid sequences in their sugar-binding acceptor subsites. This notion was derived
      from mutagenesis of amino acids of GTFA (reuteransucrase) from Lactobacillus
      reuteri strain 121 putatively involved in acceptor substrate binding. A triple
      amino acid mutation (N1134S:N1135E:S1136V) in a region immediately next to the
      catalytic Asp1133 (putative transition state stabilizing residue) converted GTFA
      from a mainly alpha-(1-->4) ( approximately 45%, reuteran) to a mainly alpha-(1-
      >6) ( approximately 80%, dextran) synthesizing enzyme. The subsequent
      introduction of mutation P1026V:I1029V, involving two residues located in a
      region next to the catalytic Asp1024 (nucleophile), resulted in synthesis of an
      alpha-glucan containing only a very small percentage of alpha-(1-->4) glucosidic
      linkages ( approximately 5%) and a further increased percentage of alpha-(1-->6)
      glucosidic linkages ( approximately 85%). This changed glucosidic linkage
      specificity was also observed in the oligosaccharide products synthesized by the
      different mutant GTFA enzymes from (iso)maltose and sucrose. Amino acids crucial
      for glucosidic linkage type specificity of reuteransucrase have been identified
      in this report. The data show that a combination of mutations in different
      regions of GTF enzymes influences the nature of both the glucan and
      oligosaccharide products. The amino acids involved most likely contribute to
      sugar-binding acceptor subsites in glucansucrase enzymes.

PMID- 15966747
TI  - Isolation and physiochemical properties of protein-rich nematode mitochondrial
      ribosomes.
AB  - In the present study, mitochondrial ribosomes of the nematode Ascaris suum were
      isolated and their physiochemical properties were compared to ribosomes of
      Escherichia coli. The sedimentation coefficient and buoyant density of A. suum
      mitochondrial ribosomes were determined. The sedimentation coefficient of the
      intact monosome was about 55 S. The buoyant density of formaldehyde-fixed
      ribosomes in cesium chloride was 1.40 g/cm(3), which suggests that the nematode
      mitoribosomes have a much higher protein composition than other mitoribosomes.
      The diffusion coefficients obtained from dynamic light scattering measurements
      were (1.48 +/- 0.04) x 10(-)(7) cm(2) s(-)(1) for 55 S mitoribosomes and (1.74 +/
      0.04) x 10(-)(7) cm(2) s(-)(1) for the 70 S E. coli monosome. The diameter of
      mitoribosomes was measured by dynamic light-scattering analysis and electron
      microscopy. Though the nematode mitoribosome has a larger size than the bacterial
      ribosome, it does not differ significantly in size from mammalian mitoribosomes.

PMID- 15966748
TI  - Miscoding events during DNA synthesis past the nitration-damaged base 8
      nitroguanine.
AB  - 8-Nitro-2'-deoxyguanosine (8-NO(2)-dG) DNA adducts are induced by the reactive
      nitrogen species and may be associated with the development of cancer in
      inflammatory tissues. To explore the miscoding potential of 8-NO(2)-dG adduct, an
      oligodeoxynucleotide containing a single 8-NO(2)-dG adduct was prepared by
      photochemical synthesis and used as a template in primer extension reactions
      catalyzed by mammalian DNA polymerases (pol). Primer extension reactions
      catalyzed by pol alpha or beta were strongly retarded at the 8-NO(2)-dG lesion; a
      fraction of primers was extended past the lesion by incorporating preferentially
      dCMP, the correct base, opposite the lesion, accompanied by lesser amounts of
      dAMP and dGMP incorporation. In contrast, primer extension reactions catalyzed by
      pol eta or a truncated form of pol kappa (pol kappaDeltaC) readily extended past
      the 8-NO(2)-dG lesion. Pol eta and kappaDeltaC showed more broad miscoding
      spectra; direct incorporations of dCMP and dAMP were observed, along with lesser
      amounts of dGMP and dTMP incorporations and deletions. The miscoding frequencies
      induced by pol eta and kappaDeltaC were at least 8 times higher than that of pol
      alpha or beta. Miscoding frequency and specificity of 8-NO(2)-dG varied depending
      on the DNA polymerases used. These observations were supported by steady-state
      kinetic studies. 8-NO(2)-dG adduct may play an important role in initiating
      inflammation driven carcinogenesis.

PMID- 15966746
TI  - Zn2+-dependent deoxyribozymes that form natural and unnatural RNA linkages.
AB  - We report Zn(2+)-dependent deoxyribozymes that ligate RNA. The DNA enzymes were
      identified by in vitro selection and ligate RNA with k(obs) up to 0.5 min(-)(1)
      at 1 mM Zn(2+) and 23 degrees C, pH 7.9, which is substantially faster than our
      previously reported Mg(2+)-dependent deoxyribozymes. Each new Zn(2+)-dependent
      deoxyribozyme mediates the reaction of a specific nucleophile on one RNA
      substrate with a 2',3'-cyclic phosphate on a second RNA substrate. Some of the
      Zn(2+)-dependent deoxyribozymes create native 3'-5' RNA linkages (with k(obs) up
      to 0.02 min(-)(1)), whereas all of our previous Mg(2+)-dependent deoxyribozymes
      that use a 2',3'-cyclic phosphate create non-native 2'-5' RNA linkages. On this
      basis, Zn(2+)-dependent deoxyribozymes have promise for synthesis of native 3'-5'
      linked RNA using 2',3'-cyclic phosphate RNA substrates, although these particular
      Zn(2+)-dependent deoxyribozymes are likely not useful for this practical
      application. Some of the new Zn(2+)-dependent deoxyribozymes instead create non
      native 2'-5' linkages, just like their Mg(2+) counterparts. Unexpectedly, other
      Zn(2+)-dependent deoxyribozymes synthesize one of three unnatural linkages that
      are formed upon the reaction of an RNA nucleophile other than a 5'-hydroxyl
      group. Two of these unnatural linkages are the 3'-2' and 2'-2' linear junctions
      created when the 2'-hydroxyl of the 5'-terminal guanosine of one RNA substrate
      attacks the 2',3'-cyclic phosphate of the second RNA substrate. The third
      unnatural linkage is a branched RNA that results from attack of a specific
      internal 2'-hydroxyl of one RNA substrate at the 2',3'-cyclic phosphate. When
      compared with the consistent creation of 2'-5' linkages by Mg(2+)-dependent
      ligation, formation of this variety of RNA ligation products by Zn(2+)-dependent
      deoxyribozymes highlights the versatility of transition metals such as Zn(2+) for
      mediating nucleic acid catalysis.

PMID- 15966749
TI  - Presence of a nucleoplasmic complex composed of the inositol 1,4,5-trisphosphate
      receptor/Ca2+ channel, chromogranin B, and phospholipids.
AB  - Although the inositol 1,4,5-trisphosphate (IP(3)) induced nuclear Ca(2+) releases
      have been shown to play key roles in nuclear functions, the presence and
      operation of the IP(3)-dependent Ca(2+) control mechanism in the nucleoplasm have
      not been shown. Recently, we found the presence of a high-capacity, low-affinity
      Ca(2+)-storage protein chromogranin B (CGB) and all three IP(3) receptor (IP(3)R)
      isoforms in the nucleoplasm, localizing widely in both the heterochromatin and
      euchromatin regions. In view of the essential role of CGB-IP(3)R coupling in
      IP(3)-dependent Ca(2+) release in the endoplasmic reticulum, the potential
      coupling between CGB and the IP(3)Rs in the nucleoplasm was investigated. Hence,
      we found in the present study the presence of a nucleoplasmic complex, which is
      composed of the IP(3)R, CGB, and phospholipids, with an estimated molecular mass
      of approximately 2-3 x 10(7) Da, suggesting the possibility of the presence of an
      IP(3)-sensitive Ca(2+) store in the nucleoplasm. Moreover, double-labeling
      immunogold electron microscope studies showed the colocalization of all three
      IP(3)R isoforms with CGB to the extent that the majority of each IP(3)R isoform
      labeling gold particles found in the nucleoplasm was literally next to the CGB
      labeling gold particles. In line with the potential existence of an IP(3)
      dependent vesicular nucleoplasmic Ca(2+) store, our preliminary results indeed
      showed a sudden release of Ca(2+) from a putative nucleoplasmic Ca(2+) store in
      response specifically to IP(3) but not to inositol 1,4-bisphosphate or inositol
      1,3,4,5-tetrakisphosphate.

PMID- 15966750
TI  - Strongly altered receptor binding properties in PP and NPY chimeras are
      accompanied by changes in structure and membrane binding.
AB  - Neuropeptide Y (NPY) and the pancreatic polypeptide (PP) are members of the
      neuropeptide Y family of hormones. They bind to the Y receptors with very
      different affinities: Whereas PP is highly selective for the Y(4) receptor, NPY
      displays highest affinites for Y(1), Y(2), and Y(5) receptor subtypes.
      Introducing the NPY segment 19-23 into PP leads to an increase in affinity at the
      Y(1) and Y(2) receptor subtypes whereas the exchange of this segment from PP into
      NPY leads to a large decrease in affinity at all receptor subtypes. PP displays a
      very stable structure in solution, with the N terminus being back-folded onto the
      C-terminal alpha-helix (the so-called PP-fold). The helix of NPY is less stable
      and the N terminus is freely diffusing in solution. The exchange of this segment,
      however, does not alter the PP-fold propensities of the chimeric peptides in
      solution. The structures of the phospholipid micelle-bound peptides serving to
      mimic the membrane-bound species display segregation into a more flexible N
      terminal region and a well-defined alpha-helical region. The introduction of the
      [19-23]-pNPY segment into hPP leads to an N-terminal extension of the alpha
      helix, now starting at Pro(14) instead of Met(17). In contrast, a truncated helix
      is observed in [(19)(-)(23)hPP]-pNPY, starting at Leu(17) instead of Ala(14). All
      peptides display moderate binding affinities to neutral membranes (K(assoc) in
      the range of 1.7 to 6.8 x 10(4) mol(-)(1) as determined by surface plasmon
      resonance) with the differences in binding being most probably related to the
      exchange of Arg-19 (pNPY) by Glu-23 (hPP). Differences in receptor binding
      properties between the chimeras and their parental peptides are therefore most
      likely due to changes in the conformation of the micelle-bound peptides.

PMID- 15966751
TI  - Kinetic stabilization of an oligomeric protein under physiological conditions
      demonstrated by a lack of subunit exchange: implications for transthyretin
      amyloidosis.
AB  - Kinetic stabilization of transthyretin (TTR) is established to prevent human
      neurodegeneration. Therefore, small molecule-mediated kinetic stabilization of
      the native state is an attractive strategy to prevent the misfolding and
      misassembly associated with TTR amyloid disease. Since the physiological
      microenvironment resulting in human TTR amyloidogenesis remains unclear, the
      conservative approach is to identify inhibitors that function under a variety of
      conditions. Small molecule kinetic stabilization of TTR has been established by
      concentration-dependent inhibition of acid-mediated amyloidogenesis and urea
      induced tetramer dissociation. Since denaturing conditions reduce the binding
      affinity of inhibitors making it difficult to predict inhibitor efficacy under
      physiological conditions, we introduce a method for quantifying kinetic
      stabilization under physiological conditions. The rate of subunit exchange
      between wild-type TTR homotetramers and wild-type TTR homotetramers tagged with
      an N-terminal acidic flag tag is dictated by the rate of tetramer dissociation to
      its monomeric subunits prior to reassembly, rendering this method ideally suited
      for assessing the kinetic stabilization of TTR imparted by small molecule binding
      and evaluating small molecule binding constants. Addition of amyloidogenesis
      inhibitors to this exchange reaction slows tetramer dissociation in a
      concentration-dependent manner, stopping dissociation at concentrations where at
      least one inhibitor is bound to each tetramer in solution. Subunit exchange
      enables the rate of tetramer dissociation and the kinetic stabilization imparted
      by small molecule binding to be evaluated under physiological conditions in which
      the TTR concentration is not reduced by aggregation or irreversible dissociation.

PMID- 15966752
TI  - Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence.
AB  - Buprenorphine is a semi-synthetic opioid derived from thebaine, a naturally
      occurring alkaloid of the opium poppy, Papaver somniferum. The pharmacology of
      buprenorphine is unique in that it is a partial agonist at the opioid mu
      receptor. Buprenorphine undergoes extensive first-pass metabolism and therefore
      has very low oral bioavailability; however, its bioavailability sublingually is
      extensive enough to make this a feasible route of administration for the
      treatment of opioid dependence. The mean time to maximum plasma concentration
      following sublingual administration is variable, ranging from 40 minutes to 3.5
      hours. Buprenorphine has a large volume of distribution and is highly protein
      bound (96%). It is extensively metabolised by N-dealkylation to norbuprenorphine
      primarily through cytochrome P450 (CYP) 3A4. The terminal elimination half-life
      of buprenorphine is long and there is considerable variation in reported values
      (mean values ranging from 3 to 44 hours). Most of a dose of buprenorphine is
      eliminated in the faeces, with approximately 10-30% excreted in urine. Naloxone
      has been added to a sublingual formulation of buprenorphine to reduce the abuse
      liability of the product. The presence of naloxone does not appear to influence
      the pharmacokinetics of buprenorphine. Buprenorphine crosses the placenta during
      pregnancy and also crosses into breast milk. Buprenorphine dosage does not need
      to be significantly adjusted in patients with renal impairment; however, since
      CYP3A activity may be decreased in patients with severe chronic liver disease, it
      is possible that the metabolism of buprenorphine will be altered in these
      patients. Although there is limited evidence in the literature to date, drugs
      that are known to inhibit or induce CYP3A4 have the potential to diminish or
      enhance buprenorphine N-dealkylation. It appears that the interaction between
      buprenorphine and benzodiazepines is more likely to be a pharmacodynamic
      (additive or synergistic) than a pharmacokinetic interaction. The relationship
      between buprenorphine plasma concentration and response in the treatment of
      opioid dependence has not been well studied. The pharmacokinetic and
      pharmacodynamic properties of buprenorphine allow it to be a feasible option for
      substitution therapy in the treatment of opioid dependence.

PMID- 15966753
TI  - Pharmacokinetics of hydroxyethyl starch.
AB  - Hydroxyethyl starch has recently become the subject of renewed interest because
      of the introduction of a new specification, hydroxyethyl starch 130/0.4, as well
      as the clinical availability of a solution using a previous hydroxyethyl starch
      type (hydroxyethyl starch 670/0.75) with a carrier other than 0.9% saline.
      Various types of hydroxyethyl starch show different pharmacokinetic behaviour.
      Since hydroxyethyl starch is a polydisperse solution acting as a colloid,
      pharmacodynamic action depends on the number of oncotically active molecules, not
      on the plasma concentration alone; therefore, solutions with a lower in vivo
      molecular weight contain more molecules at similar plasma concentrations. On the
      other hand, high plasma concentrations as well as high in vivo molecular weight
      can affect blood coagulation, especially factor VIII and von Willebrand factor.
      Hydroxyethyl starch types with a molar substitution >0.4 accumulate in plasma
      after repetitive administration, most pronounced with hetastarch (hydroxyethyl
      starch 670/0.75). Correspondingly, tissue storage as measured by (14)C tracer
      studies in animals showed significantly higher values for hydroxyethyl starch
      200/0.5 compared with hydroxyethyl starch 130/0.4 (about 4-fold at the latest
      timepoint after the last administration), and considerably higher values for
      hetastarch compared with both hydroxyethyl starch 130/0.4 and 200/0.5.
      Hydroxyethyl starch 130/0.4 does not accumulate in plasma after single- and
      multiple-dose administration in contrast to all other available hydroxyethyl
      starch specifications. Plasma clearance of hydroxyethyl starch 130/0.4 is at
      least 20-fold higher than that for hetastarch, and considerably higher than for
      pentastarch. In patients with renal insufficiency, pharmacokinetic data are only
      available for hydroxyethyl starch 130/0.4. Cumulative urinary excretion, even in
      the presence of severe non-anuric renal failure, is higher for hydroxyethyl
      starch 130/0.4 than values published for older hydroxyethyl starch
      specifications. Hydroxyethyl starch 130/0.4 may be given to patients with severe
      renal impairment as long as urine flow is preserved. The pharmacodynamics with
      respect to the volume effect does not directly mirror pharmacokinetics in the
      case of hydroxyethyl starch solutions. Equivalent volume efficacy has been proven
      for hydroxyethyl starch 130/0.4 compared with 200/0.5. Prolonged persistence of
      hydroxyethyl starch in plasma and tissues can be avoided by using rapidly
      metabolisable hydroxyethyl starch types with molar substitution <0.5. Influence
      on coagulation is minimal with hydroxyethyl starch 130/0.4, and no adverse
      effects on kidney function have been observed even with large repetitive doses
      when used according to the product information.

PMID- 15966754
TI  - Clinical pharmacokinetics of trospium chloride.
AB  - Trospium chloride, a quaternary amine with anticholinergic properties, is used
      for the treatment of overactive bladder with symptoms of urge urinary
      incontinence, urgency and urinary frequency. The pharmacokinetics of trospium
      chloride have been investigated in healthy volunteers, in patients with renal and
      hepatic impairment, and in those with symptoms of overactive bladder, after oral,
      intravenous and intravesical administration. After oral administration,
      absorption of the hydrophilic trospium chloride is slow and incomplete. Peak
      plasma concentrations (Cmax) of approximately 4 ng/mL are reached 4-5 hours after
      administration of a 20 mg immediate-release preparation. The mean bioavailability
      is approximately 10% and decreases by concomitant food intake (to a mean of 26%
      of the fasting area under the plasma concentration-time curve [AUC]). Trospium
      chloride displays dose proportional increases in AUC and Cmax after a single dose
      within the clinically relevant dose range (20-60 mg). The mean volume of
      distribution is approximately 350-800 L. The drug is minimally (mean
      approximately 10%) metabolised to spiroalcohol by hydrolysis, is 50% plasma
      protein bound and does not cross the blood-brain barrier. Urinary excretion of
      the parent compound plays a major role in the disposition of the drug, with a
      mean renal clearance of 29 L/h (accounting for approximately 70% of total
      clearance) and a mean elimination half-life ranging from 10 to 20 hours.
      Elimination of the drug is slowed in patients with renal insufficiency, and
      population pharmacokinetic modelling has demonstrated that drug clearance is
      correlated with serum creatinine concentration. Thus, dose reduction is needed in
      patients with severe renal impairment (i.e. creatinine clearance < 30 mL/min). To
      date, no clinically relevant pharmacokinetic drug-drug interactions have been
      identified; the drug does not bind to any of the drug metabolising cytochrome
      P450 enzymes. The pharmacokinetics of the drug are compatible with twice-daily
      administration. A once-daily schedule may also be appropriate, but this regimen
      needs formal clinical evaluation.

PMID- 15966755
TI  - Steady-state pharmacokinetics of a novel extended-release metformin formulation.
AB  - BACKGROUND AND OBJECTIVE: Metformin is an effective treatment for type 2 diabetes
      mellitus. The pharmacokinetic characteristics of the conventional immediate
      release (IR) formulation of metformin (Glucophage), however, necessitate two- or
      three-times-daily dosing. Development of a novel extended-release (XR)
      formulation of metformin (Glucophage XR) using GelShield Diffusion System
      technology provides a once-daily dosing option. The objective of this study was
      to assess the steady-state pharmacokinetics of metformin XR tablets. STUDY
      DESIGN: This was an open-label, multiple-dose, five-regimen, two-sequence
      clinical study lasting 5 weeks. METHODS: Subjects were 16 healthy volunteers aged
      18-40 years. Three 1-week regimens of metformin XR (500, 1000 and 1500 mg once
      daily) were administered sequentially. Subjects were alternately given either
      metformin XR 2000 mg once daily or metformin IR 1000 mg twice daily during weeks
      4 and 5. The pharmacokinetic properties of metformin XR were assessed on two
      separate days at steady state and compared with those of metformin IR. RESULTS:
      Absorption of metformin XR was slower than that of metformin IR (time to maximum
      plasma concentration = 7 versus 3 hours). Maximum plasma concentrations (Cmax)
      following the administration of metformin XR 2000 mg once daily was 36% higher
      than that following the evening dose of metformin IR 1000 mg twice daily. The
      extent of absorption, determined by area under the plasma concentration-time
      curve (AUC), was equivalent for both formulations. The mean accumulation ratio of
      metformin XR was 1.0, indicating no accumulation with multiple-dose
      administration. Intrasubject variabilities in Cmax and AUC of metformin were
      comparable between metformin XR and metformin IR. This novel formulation of
      metformin XR was well tolerated at single doses up to 2000 mg once daily for 7
      days, and adverse events were similar to those reported with metformin IR.
      CONCLUSION: The pharmacokinetic parameters of metformin XR tablet using GelShield
      Diffusion System technology were similar to those of metformin IR. Metformin XR
      was well tolerated at single doses up to 2000 mg once daily.

PMID- 15966756
TI  - Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects
      of levo-alpha-acetylmethadol: importance of clinical investigations to validate
      in vitro drug metabolism studies.
AB  - OBJECTIVE: Levo-alpha-acetylmethadol (LAAM, levacetylmethadol) is a long-acting
      opioid agonist used for the prevention of opioid withdrawal. LAAM undergoes
      sequential N-demethylation to norLAAM and dinorLAAM, which are more potent and
      longer-acting than LAAM. Hepatic and intestinal microsomal N-demethylation in
      vitro is catalysed mainly by cytochrome P450 (CYP) 3A4; however, the role of
      CYP3A in LAAM disposition in humans in vivo is unknown. This investigation tested
      the hypothesis that CYP3A induction (or inhibition) would increase (or decrease)
      LAAM metabolism and bioactivation and, thus, clinical effects. It also related
      changes in LAAM disposition during enzyme inhibition or induction to any changes
      in pharmacological effect. METHODS: Healthy volunteers (n = 13) completed the
      three-way, randomised, balanced crossover study. Subjects received oral LAAM
      (0.25 mg/kg) after CYP3A induction (rifampicin [rifampin]), inhibition
      (troleandomycin) or nothing (controls). Plasma and urine LAAM, norLAAM and
      dinorLAAM were determined by electrospray high-performance liquid
      chromatography/mass spectrometry (HPLC/MS). Dark-adapted pupil diameter change
      from baseline (miosis) was the LAAM effect measure. Results were analysed by
      noncompartmental methods and by a combined pharmacokinetic/pharmacodynamic model.
      RESULTS: Compared with controls, CYP3A induction (or inhibition) decreased (or
      increased) plasma LAAM concentrations and mean area under the plasma
      concentration-time curve from time zero to infinity (AUC(infinity) 199 +/- 91
      [control] versus 11.3 +/- 4.0 [rifampicin] and 731 +/- 229 ng . h/mL
      [troleandomycin]; p < 0.05), and increased (or decreased) median formation
      clearances of norLAAM (1740 versus 14 100 and 302 mL/h/kg; p < 0.05) and
      dinorLAAM (636 versus 7840 and 173 mL/h/kg; p < 0.05). Surprisingly, however,
      CYP3A induction (or inhibition) decreased (or increased) mean plasma metabolite
      AUC from 0 to 96 hours (AUC(96)) [norLAAM + dinorLAAM] (859 +/- 241 versus 107 +/
      48 and 1185 +/- 179 ng . h/mL; p < 0.05) and clinical effects (mean miosis
      AUC(96) 128 +/- 40 versus 22.5 +/- 14.9 and 178 +/- 81 mm . h; p < 0.05).
      Clinical effects were best correlated with plasma norLAAM concentrations.
      CONCLUSION: CYP3A mediates human LAAM N-demethylation and bioactivation to
      norLAAM and dinorLAAM in vivo. Paradoxically, however, CYP3A induction decreased
      and inhibition increased LAAM active metabolite concentrations and clinical
      effects. This suggests a CYP3A-mediated metabolic pathway leading to inactive
      metabolites, which predominates over CYP3A-dependent bioactivation. These results
      highlight the need for clinical investigations to validate in vitro drug
      metabolism studies.

PMID- 15966757
TI  - Modafinil influences the pharmacokinetics of intravenous cocaine in healthy
      cocaine-dependent volunteers.
AB  - OBJECTIVE: To determine if modafinil, a putative treatment for cocaine
      dependence, influences the pharmacokinetics of intravenous cocaine in otherwise
      healthy cocaine-dependent volunteers. METHODS: Cocaine 20 or 40 mg was
      administered intravenously on consecutive days over 1 minute at baseline and
      after modafinil administration at each of two dosages of 400 and 800 mg/day for 7
      days. RESULTS: Twelve subjects completed the clinical protocol. Compared with
      baseline, the cocaine peak plasma concentration was decreased after both the 20
      and 40 mg cocaine infusions, but the reduction was only statistically significant
      after the 40 mg cocaine infusion (p < 0.01 after modafinil 400 mg/day; p < 0.05
      after modafinil 800 mg/day). The area under the cocaine plasma concentration-time
      curve from 0 to 180 minutes (AUC180) was significantly decreased by modafinil
      administration (p < 0.01 and p < 0.001 for modafinil 400 and 800 mg/day,
      respectively, for the cocaine 20mg dose; p < 0.001 for the cocaine 40 mg dose at
      both modafinil levels). There were no significant changes in total AUC, clearance
      or elimination half-life of cocaine. CONCLUSION: This study did not find evidence
      for a harmful pharmacokinetic interaction between modafinil and cocaine. In
      contrast, long-term administration of modafinil significantly decreased systemic
      exposure to cocaine during the first 180 minutes following intravenous cocaine
      administration.

PMID- 15966758
TI  - Relationship between minimum inhibitory concentration and stationary
      concentration revisited: growth rates and minimum bactericidal concentrations.

PMID- 15966759
TI  - Mesenchymal stem cells support expansion of in vitro irradiated CD34(+) cells in
      the presence of SCF, FLT3 ligand, TPO and IL3: potential application to
      autologous cell therapy in accidentally irradiated victims.
AB  - Ex vivo expansion of residual autologous hematopoietic stem and progenitor cells
      collected from victims soon after accidental irradiation (autologous cell
      therapy) may represent an additional or alternative approach to cytokine therapy
      or allogeneic transplantation. Peripheral blood CD34+ cells could be a useful
      source of cells for this process provided that collection and ex vivo expansion
      of hematopoietic stem and progenitor cells could be optimized. Here we
      investigated whether mesenchymal stem cells could sustain culture of irradiated
      peripheral blood CD34+ cells. In vitro irradiated (4 Gy 60Co gamma rays) or
      nonirradiated mobilized peripheral blood CD34+ cells from baboons were cultured
      for 7 days in a serum-free medium supplemented with stem cell
      factor+thrombopoietin+interleukin 3+FLT3 ligand (50 ng/ml each) in the presence
      or absence of mesenchymal stem cells. In contrast to cultures without mesenchymal
      stem cells, irradiated CD34+ cells cultured with mesenchymal stem cells displayed
      cell amplification, i.e. CD34+ (4.9-fold), CD34++ (3.8-fold), CD34++/Thy-1+ (8.1
      fold), CD41+ (12.4-fold) and MPO+ (50.6-fold), although at lower levels than in
      nonirradiated CD34+ cells. Fourteen times more clonogenic cells, especially BFU
      E, were preserved when irradiated cells were cultured on mesenchymal stem cells.
      Moreover, we showed that the effect of mesenchymal stem cells is related mainly
      to the reduction of apoptosis and involves cell-cell contact rather than
      production of soluble factor(s). This experimental model suggests that
      mesenchymal stem cells could provide a crucial tool for autologous cell therapy
      applied to accidentally irradiated victims.

PMID- 15966760
TI  - Different radiosensitive megakaryocytic progenitor cells exist in steady-state
      human peripheral blood.
AB  - CD34 antigen is a novel marker for human hematopoietic stem/progenitor cells. In
      the present study, two cell fractions, CD34low and CD34high, were prepared from
      steady-state human peripheral blood on the basis of CD34 antigen expression. The
      colony-forming unit megakaryocytes (CFU-Meg) contained in each cell fraction were
      compared for X-radiation sensitivity and cytokine action. The content of
      CD34+CD45+ cells in the CD34low and CD34high cell fractions was 74.8% and 88.8%,
      respectively, and the frequency of thrombopoietin (TPO)-supported CFU-Meg in the
      CD34low cell fraction was 1.9 times higher than that in CD34high. The CFU-Meg in
      CD34high were more radiosensitive than those in CD34low, indicating that steady
      state human peripheral blood contains different types of CFU-Meg. However, no
      significant differences were observed between cell fractions in the radiation
      survival curves of CFU-Meg stimulated by TPO plus cytokines except granulocyte
      colony-stimulating factor (G-CSF). TPO plus interleukin 3 was the optimal
      combination for survival of both types of CFU-Meg after X irradiation. The
      present study also demonstrated that TPO plus G-CSF is able to increase the
      survival of irradiated CD34low CFU-Meg. These results suggest that two
      megakaryocytic progenitor populations with different radiosensitivity and
      cytokine responses are found in steady-state human peripheral blood.

PMID- 15966761
TI  - Gene expression profiles of normal human fibroblasts after exposure to ionizing
      radiation: a comparative study of low and high doses.
AB  - Several types of cellular responses to ionizing radiation, such as the adaptive
      response or the bystander effect, suggest that low-dose radiation may possess
      characteristics that distinguish it from its high-dose counterpart. Accumulated
      evidence also implies that the biological effects of low-dose and high-dose
      ionizing radiation are not linearly distributed. We have investigated, for the
      first time, global gene expression changes induced by ionizing radiation at doses
      as low as 2 cGy and have compared this to expression changes at 4 Gy. We applied
      cDNA microarray analyses to G1-arrested normal human skin fibroblasts subjected
      to X irradiation. Our data suggest that both qualitative and quantitative
      differences exist between gene expression profiles induced by 2 cGy and 4 Gy. The
      predominant functional groups responding to low-dose radiation are those involved
      in cell-cell signaling, signal transduction, development and DNA damage
      responses. At high dose, the responding genes are involved in apoptosis and cell
      proliferation. Interestingly, several genes, such as cytoskeleton components ANLN
      and KRT15 and cell-cell signaling genes GRAP2 and GPR51, were found to respond to
      low-dose radiation but not to high-dose radiation. Pathways that are specifically
      activated by low-dose radiation were also evident. These quantitative and
      qualitative differences in gene expression changes may help explain the non
      linear correlation of biological effects of ionizing radiation from low dose to
      high dose.

PMID- 15966762
TI  - Identification of differentially expressed genes contributing to radioresistance
      in lung cancer cells using microarray analysis.
AB  - Radiotherapy has played a key role in the control of tumor growth in many cancer
      patients. It is usually difficult to determine what fraction of the tumor cell
      population is radioresistant after a course of radiotherapy. The response of
      tumor cells to radiation is believed to be accompanied by complex changes in the
      gene expression pattern. It may be possible to use these to sensitize
      radioresistant tumor cells and improve radiocurability. Based on the biological
      effects of ionizing radiation, in the present study, we developed one
      oligonucleotide microarray to analyze the expression of 143 genes in cells of two
      lung cancer cell lines with different radiosensitivities. Compared to NCI-H446
      cells, expression of 18 genes significantly increased the basal levels in the
      radioresistant A549 cells, in which eight genes were up-regulated and 10 genes
      were down-regulated. In A549 cells irradiated with 5 Gy, 22 (19 up-regulated and
      three down-regulated) and 26 (eight up-regulated and 18 down-regulated)
      differentially expressed genes were found 6 and 24 h after irradiation,
      respectively. In NCI-H446 cells, the expression of 17 (nine up-regulated and
      eight down-regulated) and 18 (six up-regulated and 12 down-regulated) genes was
      altered 6 and 24 h after irradiation, respectively. RT-PCR was performed, and we
      found that MDM2, BCL2, PKCZ and PIM2 expression levels were increased in A549
      cells and decreased in NCI-H446 cells after irradiation. Genes involved in DNA
      repair, such as XRCC5, ERCC5, ERCC1, RAD9A, ERCC4 and the gene encoding DNA-PK,
      were found to be increased to a higher level in A549 cells than in NCI-H446
      cells. Antisense suppression of MDM2 resulted in increased radiosensitivity of
      A549 cells. Taken together, these results demonstrate the possibility that a
      group of genes involved in DNA repair, regulation of the cell cycle, cell
      proliferation and apoptosis is responsible for the different radioresistance of
      these two lung cancer cells. This list of genes may be useful in attempts to
      sensitize the radioresistant lung cancer cells.

PMID- 15966763
TI  - X irradiation induces the proapoptotic state independent of the loss of
      clonogenic ability in Chinese hamster V79 cells.
AB  - The clonogenic ability (reproductive cell death) of Chinese hamster V79 cells was
      measured after treatment with X radiation and a newly developed anti-cancer drug,
      1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd, TAS106). Amplification
      in the loss of clonogenicity was observed compared to that obtained for cells
      exposed to X rays alone. Addition of benzyloxycarbonyl-val-ala-asp
      fluoromethylketone (Z-VAD-FMK), a broad-spectrum caspase inhibitor, attenuated
      the increased lethality, but the dose-response curve obtained was found to merely
      revert to that obtained for cells exposed to X rays alone. Flow cytometric
      analysis showed that the number of cells arrested at the G2/M phase by X
      irradiation was decreased by co-treatment with TAS106, and instead the number of
      cells in the sub-G1 phase increased. Western blot analysis proved that TAS106
      treatment down-regulated the expression of the G2/M arrest-related proteins
      cyclin B1, phospho-CDC2 and WEE1. From these results, it was concluded that (1)
      no apoptosis was included in the dose-response curve obtained from cells exposed
      to X rays alone, (2) X radiation induced a potentially apoptotic (proapoptotic)
      state in cells independent of the loss of their clonogenic ability, and (3)
      TAS106 enhanced the loss of their clonogenic ability by converting the
      proapoptotic cells to apoptotic cells through the abrogation of arrest at the
      G2/M phase.

PMID- 15966764
TI  - Cytoskeletal reorganization and altered phagocytotic ability in primary cultures
      of rainbow trout hemopoietic tissue exposed to low-level ionizing radiation.
AB  - It has long been known that the hematopoietic tissue of mammals is one of the
      most radiosensitive tissues. In vitro studies on prawns have also shown that low
      doses of radiation have an extremely deleterious effect on cells cultured from
      this animal's blood-forming tissues. This raises questions about the relative
      effects of radiation in animals of different species. One of the most important
      aquatic animals, from both an economic and an ecological point of view, is the
      fish. With this in mind, primary cultures of the blood-forming tissues of rainbow
      trout were exposed to radiation followed by a morphological comparison between
      control and irradiated cultures. The cultured cells were characterized as
      macrophages after incubation with apoptotic human polymorphonuclear leukocytes
      and were classified as phagocytotic leukocytes. These cells were found in two
      morphological forms, stretched and rounded. It was shown that there was a
      commensurate increase in the number of stretched cells after irradiation.
      Radiation was also shown to cause a dose-dependent increase in the amounts of
      apoptosis in these cells over time. The phagocytotic efficacy of these cells was
      shown to inhibited by the exposure to low doses of radiation.

PMID- 15966765
TI  - Accelerated telomere shortening and telomere abnormalities in radiosensitive cell
      lines.
AB  - We examined telomere maintenance in cells of 11 primary fibroblast cell lines
      with differing genetic defects that confer sensitivity to ionizing radiation.
      These included cell lines derived from patients with ataxia telangiectasia,
      Nijmegen breakage syndrome, Fanconi anemia, defective Artemis, DNA ligase I and
      DNA ligase IV, an immunodeficient patient with a defect in DNA double-strand
      break repair, and a patient diagnosed with xeroderma pigmentosum who, in
      addition, showed severe clinical sensitivity to ionizing radiation. Our results,
      based on Southern blot, flow-FISH and Q-FISH (quantitative FISH) measurements,
      revealed an accelerated rate of telomere shortening in most cell lines derived
      from the above patients compared to cell lines from normal individuals or a cell
      line isolated from a heterozygotic parent of one radiosensitive patient. This
      accelerated telomere shortening was accompanied by the formation of chromatin
      bridges in anaphase cells, indicative of the early loss of telomere capping
      function and in some cases low levels of chromosome abnormalities in metaphase
      cells. We also analyzed telomere maintenance in mouse embryonic stem cells
      deficient in Brca1, another defect that confers radiosensitivity. Similarly,
      these cells showed accelerated telomere shortening and mild telomere dysfunction
      in comparison to control cells. Our results suggest that mechanisms that confer
      sensitivity to ionizing radiation may be linked with mechanisms that cause
      telomere dysfunction.

PMID- 15966766
TI  - Modulation of DNA damage by pentoxifylline and alpha-tocopherol in skin
      fibroblasts exposed to Gamma rays.
AB  - Previous in vivo studies showed the combination pentoxifylline (PTX) and alpha
      tocopherol was highly efficient in reducing late radiation-induced skin damage.
      The present work aimed at investigating the molecular and cellular mechanisms
      involved in the effects of this combination. Primary cultures of confluent dermal
      fibroblasts were gamma-irradiated in the presence of PTX and trolox (Tx), the
      water-soluble analogue of alpha-tocopherol. Drugs were added either before or
      after radiation exposure and were maintained over time. Their antioxidant
      capacity and their effect on radiation-induced ROS production was assessed
      together with cell viability and clonogenicity. DNA damage formation was assessed
      by the alkaline comet assay and by the micronucleus (MN) test. Cell cycle
      distribution was also determined. The combination of PTX/ Tx was shown to reduce
      both immediate and late ROS formation observed in cells after irradiation.
      Surprisingly, decrease in DNA strand breaks measured by the comet assay was
      observed any time drugs were added. In addition, the micronucleus test revealed
      that for cells irradiated with 10 Gy, a late significant increase in MN formation
      occurred. The combination of PTX/Tx was shown to be antioxidant and to decrease
      radiation-induced ROS production. The observed effects on DNA damage at any time
      the drugs were added suggest that PTX/Tx could interfere with the DNA repair
      process.

PMID- 15966767
TI  - Evidence for complexity at the nanometer scale of radiation-induced DNA DSBs as a
      determinant of rejoining kinetics.
AB  - The rejoining kinetics of double-stranded DNA fragments, along with measurements
      of residual damage after postirradiation incubation, are often used as indicators
      of the biological relevance of the damage induced by ionizing radiation of
      different qualities. Although it is widely accepted that high-LET radiation
      induced double-strand breaks (DSBs) tend to rejoin with kinetics slower than low
      LET radiation-induced DSBs, possibly due to the complexity of the DSB itself, the
      nature of a slowly rejoining DSB-containing DNA lesion remains unknown. Using an
      approach that combines pulsed-field gel electrophoresis (PFGE) of fragmented DNA
      from human skin fibroblasts and a recently developed Monte Carlo simulation of
      radiation-induced DNA breakage and rejoining kinetics, we have tested the role of
      DSB-containing DNA lesions in the 8-kbp-5.7-Mbp fragment size range in
      determining the DSB rejoining kinetics. It is found that with low-LET X rays or
      high-LET alpha particles, DSB rejoining kinetics data obtained with PFGE can be
      computer-simulated assuming that DSB rejoining kinetics does not depend on
      spacing of breaks along the chromosomes. After analysis of DNA fragmentation
      profiles, the rejoining kinetics of X-ray-induced DSBs could be fitted by two
      components: a fast component with a half-life of 0.9+/-0.5 h and a slow component
      with a half-life of 16+/-9 h. For alpha particles, a fast component with a half
      life of 0.7+/-0.4 h and a slow component with a half-life of 12+/-5 h along with
      a residual fraction of unrepaired breaks accounting for 8% of the initial damage
      were observed. In summary, it is shown that genomic proximity of breaks along a
      chromosome does not determine the rejoining kinetics, so the slowly rejoining
      breaks induced with higher frequencies after exposure to high-LET radiation
      (0.37+/-0.12) relative to low-LET radiation (0.22+/-0.07) can be explained on the
      basis of lesion complexity at the nanometer scale, known as locally multiply
      damaged sites.

PMID- 15966768
TI  - Defining the pHi-hyperthermia sensitivity relationship for the RIF-1 tumor in
      vivo: a 31P MR spectroscopy study.
AB  - This study quantifies the enhancement of the therapeutic efficacy of hyperthermia
      resulting from an acutely acidified and accurately monitored intracellular pH
      (pHi) in a mouse tumor model in vivo. Metabolic manipulation of the physiology of
      RIF-1 tumor (subcutaneous, on the hind flanks of female C3H/HeJ mice) achieved by
      i.p. bolus injection of glucose (glycolytic tumor acidification) or 3-O
      methylglucose (non-glycolytic tumor acidification) was monitored by 31P magnetic
      resonance (31P MR) prior to, during and up to 1 h after localized hyperthermia.
      The pre-hyperthermia 31P MR-observable metabolic parameter that correlates most
      strongly with thermal sensitivity is pHi. Thermal sensitivity increases linearly
      with decreasing pHi regardless of the mechanism (glycolytic or non-glycolytic) of
      metabolic manipulation. The quantitative relationship is described by
      log10(SF)/EQ43=0.0079 pHi,preHT -0.0606 (R=0.63, P<0.0001), where EQ43 is the
      thermal heat dose delivered to the tumor (in units of equivalent minutes at 42.5
      degrees C), pHi,preHT is the intracellular pH immediately prior to hyperthermia,
      and SF is the surviving fraction. The therapeutic enhancement is not as dramatic
      as expected based upon previously reported in vitro studies but is generally
      consistent with other in vivo studies. The method still represents a viable
      strategy for enhancing the therapeutic efficacy of hyperthermia, especially when
      used in combination with other therapeutic modalities.

PMID- 15966769
TI  - Animal models for radiation injury, protection and therapy.
AB  - Current events throughout the world underscore the growing threat of different
      forms of terrorism, including radiological or nuclear attack. Pharmaceutical
      products and other approaches are needed to protect the civilian population from
      radiation and to treat those with radiation-induced injuries. In the event of an
      attack, radiation exposures will be heterogeneous in terms of both dose and
      quality, depending on the type of device used and each victim's location relative
      to the radiation source. Therefore, methods are needed to protect against and
      treat a wide range of early and slowly developing radiation-induced injuries.
      Equally important is the development of rapid and accurate biodosimetry methods
      for estimating radiation doses to individuals and guiding clinical treatment
      decisions. Acute effects of high-dose radiation include hematopoietic cell loss,
      immune suppression, mucosal damage (gastrointestinal and oral), and potential
      injury to other sites such as the lung, kidney and central nervous system (CNS).
      Long-term effects, as a result of both high- and low-dose radiation, include
      dysfunction or fibrosis in a wide range of organs and tissues and cancer. The
      availability of appropriate types of animal models, as well as adequate numbers
      of animals, is likely to be a major bottleneck in the development of new or
      improved radioprotectors, mitigators and therapeutic agents to prevent or treat
      radiation injuries and of biodosimetry methods to measure radiation doses to
      individuals.

PMID- 15966771
TI  - Cell culture models of the respiratory tract relevant to pulmonary drug delivery.
AB  - The respiratory tract holds promise as an alternative site of drug delivery due
      to fast absorption and rapid onset of drug action, with avoidance of hepatic and
      intestinal first-pass metabolism as an additional benefit compared to oral drug
      delivery. At present, the pharmaceutical industry increasingly relies on
      appropriate in vitro models for the faster evaluation of drug absorption and
      metabolism as an alternative to animal testing. This article reviews the various
      existing cell culture systems that may be applied as in vitro models of the human
      air-blood barrier, for instance, in order to enable the screening of large
      numbers of new drug candidates at low cost with high reliability and within a
      short time span. Apart from such screening, cell culture-based in vitro systems
      may also contribute to improve our understanding of the mechanisms of drug
      transport across such epithelial tissues, and the mechanisms of action how
      advanced drug carriers, such as nanoparticles or liposomes, can help to overcome
      these barriers. After all, the increasing use and acceptance of such in vitro
      models may lead to a significant acceleration of the drug development process by
      facilitating the progress into clinical studies and product registration.

PMID- 15966772
TI  - Pharmacological approach to evaluate aerosol pulmonary deposition.
AB  - Drug delivery to the lung in vivo may be assessed using pharmacokinetic or
      pharmacodynamic techniques. The choice of method depends on drug class
      specificities. Pharmacokinetic determination of deposition to the lung for drugs
      without hepatic first-pass effect, such as short acting beta2-agonists, has to be
      done shortly after inhalation to minimize the effect of gastrointestinal
      absorption. For medication undergoing important hepatic first-pass
      metabolisation, such as inhaled corticosteroid, plasma concentration indirectly
      reflects bronchial deposition. The pharmacodynamic profile should be assessed
      through clinical effects and adverse events induced by inhaled drugs. Dose
      ranking of lung deposition for bronchodilators requires patient selection with
      sufficient bronchial obstruction to maintain room for improvement after the first
      dose. To assess dose effect relationship between inhaled corticosteroid, the
      Finney parallel line bioassay is the reference method with a study period of at
      least 6 weeks. Analysis of side effects with high doses of beta2-agonists or
      inhaled corticosteroids may also be used to compare lung deposition. Finally,
      pharmacological evaluation of lung deposition provides complementary information
      to scintigraphic studies, based on their clinical relevance.

PMID- 15966770
TI  - The cell cycle-regulated genes of Schizosaccharomyces pombe.
AB  - Many genes are regulated as an innate part of the eukaryotic cell cycle, and a
      complex transcriptional network helps enable the cyclic behavior of dividing
      cells. This transcriptional network has been studied in Saccharomyces cerevisiae
      (budding yeast) and elsewhere. To provide more perspective on these regulatory
      mechanisms, we have used microarrays to measure gene expression through the cell
      cycle of Schizosaccharomyces pombe (fission yeast). The 750 genes with the most
      significant oscillations were identified and analyzed. There were two broad waves
      of cell cycle transcription, one in early/mid G2 phase, and the other near the
      G2/M transition. The early/mid G2 wave included many genes involved in ribosome
      biogenesis, possibly explaining the cell cycle oscillation in protein synthesis
      in S. pombe. The G2/M wave included at least three distinctly regulated clusters
      of genes: one large cluster including mitosis, mitotic exit, and cell separation
      functions, one small cluster dedicated to DNA replication, and another small
      cluster dedicated to cytokinesis and division. S. pombe cell cycle genes have
      relatively long, complex promoters containing groups of multiple DNA sequence
      motifs, often of two, three, or more different kinds. Many of the genes,
      transcription factors, and regulatory mechanisms are conserved between S. pombe
      and S. cerevisiae. Finally, we found preliminary evidence for a nearly genome
      wide oscillation in gene expression: 2,000 or more genes undergo slight
      oscillations in expression as a function of the cell cycle, although whether this
      is adaptive, or incidental to other events in the cell, such as chromatin
      condensation, we do not know.

PMID- 15966773
TI  - A comparison of standard inhalers for asthma with and without alcohol as the
      propellant on the measurement of alcohol in breath.
AB  - Because most bronchodilator inhalers contain propellant gases or a small amount
      of ethanol as a co-solvent, the potential for these products to generate false
      readings on a evidential breath alcohol instrument was evaluated in 69 volunteers
      with clinically stable asthma. All subjects underwent a breath test on an
      infrared breath alcohol analyzer (Alcotest 7110, Drager, Lubeck, Germany) before
      the use of the asthma inhaler and 1 and 5 min after inhalation. The effects of
      antiasthmatic medications delivered by metered dose inhalers (MDIs) with alcohol
      as a vehicle, alcohol-free MDIs, and dry powder inhalers were assessed in
      homogeneous groups of four to five patients. All subjects were alcohol-free on
      the preliminary breath test. One minute after inhalation, negative readings were
      only observed in 25 (36.2%) of subjects. In 62.3% of patients, apparent alcohol
      results were considered interferences or unstable readings by the breath-test
      instrument. One subject showed a final positive breath alcohol level (0.07 mg/L).
      After the use of dry powder inhalers, valid results without interferences were
      obtained. However, 89.6% of patients in which bronchodilators were delivered by
      MDIs (with propellant gases in the aerosol) showed altered partial readings and
      labeled the final output as "invalid," but tests performed 5 min after the use of
      inhalers were valid and correct in all cases. MDIs with propellants as a vehicle
      may cause false positive breath alcohol readings in some patients. These effects
      are transient and may be prevented by a 5-10-min interval between the use of MDIs
      and breath alcohol testing.

PMID- 15966774
TI  - Safety of pulmonary administration of gemcitabine in rats.
AB  - The purpose of this research was to evaluate the safety of pulmonary
      administration of gemcitabine and to determine the maximum tolerated dose by
      weekly pulmonary administrations in an animal model. Five groups of eight Wistar
      rats received gemcitabine at doses of 2, 4, 6, or 8 mg/kg or the vehicle solution
      by endotracheal spray with scintigraphic imaging of lung deposition. In order to
      document the safety of digestive exposure, five groups of eight rats received
      gemcitabine at the same dosages or the vehicle solution by gavage. Nine weekly
      sessions were planned, and blood cell counts and histological examinations were
      performed in live animals at day 64. Scintigraphic imaging confirmed pulmonary
      deposition in 310 of 316 spray administrations (98%) with homogeneous pattern of
      deposition. The maximum tolerated dose of gemcitabine by pulmonary administration
      was 4 mg/kg. At this dosage, administered once a week for 9 consecutive weeks,
      there were no chemotherapy-related deaths and no clinical, histological, or
      hematological signs of toxicity except for a decrease in platelet and red blood
      cell counts, with no clinical significance. The toxicity of gemcitabine was
      higher via oral than lung delivery in terms of weight loss and white blood cell
      toxicity at dosages of 2, 4, and 6 mg/kg. Pulmonary administration of gemcitabine
      is safe in rats at a maximum tolerated dose of 4 mg/kg once a week for 9 weeks.
      At an equivalent dosage, the toxicity of gemcitabine is lower by lung than oral
      administration.

PMID- 15966775
TI  - Numerical simulation of air flow and medical-aerosol distribution in an
      innovative nebulizer hood.
AB  - The use of a hood to administer therapeutic aerosols to wheezy infants has many
      advantages and was found as efficient as administration using a mask. The aim of
      the present study is to investigate numerically the airflow induced drug
      dispersion inside the hood. Drug droplet dispersion is examined with respect to
      three breathing phases: inspiration, expiration, and apnea. The governing
      equations describing the airflow and the trajectories of drug droplets were
      solved using the FLUENT 6.1 Computational Fluid Dynamics (CFD) software package.
      The geometry and mesh were generated with the GAMBIT package. The velocity field
      of the air and the trajectories of drug droplets inside the funnel--the tube that
      delivers the drug from the nebulizer to the infant's mouth--and close to its exit
      are robust and do not show any appreciable differences among the three breathing
      phases studied. However, in other parts of the hood, air velocity, and particle
      motion largely depend on the infant's breathing and physiological state. The
      efficiency of drug delivery to the mouth during inspiration is found to be as
      high as 84%, whereas it is much smaller in the other two (common) breathing
      phases examined. Our results may be utilized to improve the hood design and to
      increase its efficacy for administration of aerosolized medications to infants.

PMID- 15966776
TI  - Investigating the evaporation of metered-dose inhaler formulations in humid air:
      single droplet experiments.
AB  - The effect of excipients and humidity on the evaporation of propellant from
      metered-dose inhaler (MDI) formulations was examined by means of single, pendant
      droplet experiments. Droplets of pure hydrofluoroalkane (HFA) 227ea propellant,
      as well as propellant-ethanol and propellant-ethanol-sorbitan-trioleate mixtures,
      were suspended by needle into a conditioned viewing chamber. Droplet evaporation
      was recorded through a microscope-coupled CCD camera for each mixture, with
      viewing chamber conditions of 37 degrees C and either 100% or <10% relative
      humidity, over a size range from approximately 4 to approximately 1 microL.
      Volume versus time data was collected for each droplet through digital processing
      of image frames, according to Axisymmetric Drop Shape Analysis (ADSA) routines.
      No significant difference was observed in the rate of change of droplet volume
      (i.e., evaporation rate) between dry and humid conditions, regardless of the
      formulation studied. In addition, the rate of propellant evaporation appeared
      unchanged despite the addition of 15% w/w ethanol to HFA 227ea, while only slight
      reductions in evaporation rate were observed for a mixture containing 15% ethanol
      and 0.2% sorbitan trioleate. It was concluded that the rate of evaporation of
      propellant from HFA-based MDI formulations likely remains unchanged in the
      presence of high levels of humidity. Therefore, alternative explanations should
      be explored to explain the increase in MDI particle deposition in highly humid,
      confined airways.

PMID- 15966777
TI  - In vitro determination of the optimal particle size for nebulized aerosol
      delivery to infants.
AB  - We investigated the in vitro influence of breathing patterns on lung dose (LD)
      and particle size distribution in an infant upper airway cast model in order to
      determine the optimal particle size for nebulized aerosol delivery to infants.
      Budesol (nebulizer solution of budesonide) delivery from a perforated vibrating
      membrane nebulizer (eFlow Baby functional prototype) through an upper airway cast
      of a nine month old infant (SAINT-model) was measured at a fixed respiratory rate
      (RR) of 30 breaths per minute (bpm) and a tidal volume (Vt) of 50, 100, and 200
      mL, respectively, and at a fixed Vt of 100 mL and a RR of 30, 60, and 78 bpm,
      respectively. LD expressed as a percentage of the nominal dose (ND; range, 5.8
      30.3%) decreased with increasing Vt (p < 0.001) and with increasing RR (p <
      0.001). Median mass aerodynamic diameter (MMAD) after passage (range, 2.4-3.4
      microm) through the upper airway cast showed a negative correlation with
      increasing Vt (p < 0.001) and with increasing RR (p = 0.015). Particles available
      as LD for all simulated breathing pattern showed a particle size distribution
      with a MMAD of 2.4 microm and a geometric standard deviation (GSD) of 1.56. From
      our in vitro study, we conclude that the optimal particle size for nebulized
      aerosols for inhalation therapy for infants should have a MMAD of <2.4 microm.

PMID- 15966779
TI  - The role of health advocacy in disease management.

PMID- 15966780
TI  - A matched-cohort study of selected clinical and utilization outcomes for an
      asthma care support program.
AB  - Estimating the economic and clinical impact of asthma disease management programs
      traditionally has relied on non-experimental designs and employed matching or
      stratification methods with limited success. Selecting similar comparison
      subjects is problematic since subjects must be compared across numerous
      pretreatment factors. In cases where treatment and comparison subjects differ
      greatly on observed characteristics, conclusions may be particularly sensitive to
      an incorrectly specified model used for matching. A propensity score method
      constructs matched samples of treated-control pairs, addresses program selection
      bias, and reduces bias in estimates of treatment effects. To investigate the
      program effects of an asthma care support program delivered to high-risk
      asthmatics (persons with a previous inpatient admission, emergency department
      [ED] visit, or observation visit), we conducted a matched-cohort study on 196
      participants. Using administrative claims data and selected clinical indicators,
      we analyzed hospitalization, ED, and physician office visit rates to estimate
      effects of program enrollment. Total hospitalizations, asthma-related
      hospitalizations, bed days, and ED visits for participants were lower and
      statistically different from that of the matched-cohort group during the program
      period, suggesting the beneficial effects of monitoring, education, and
      counseling activities for participants. Where controlled randomized clinical
      trials cannot be performed because of ethical, cost, or feasibility issues, the
      use of propensity scores provides an alternative for estimating treatment effects
      using observational data. This study employs a propensity score-matching
      methodology to select a subset of comparison units most comparable to treatment
      units, and documents the beneficial outcomes of participation in an asthma care
      support program.

PMID- 15966781
TI  - Treatment effects model for assessing disease management: measuring outcomes and
      strengthening program management.
AB  - This paper describes an analytical methodology for obtaining statistically
      unbiased outcomes estimates for programs in which participation decisions may be
      correlated with variables that impact outcomes. This methodology is particularly
      useful for intraorganizational program evaluations conducted for business
      purposes. In this situation, data is likely to be available for a population of
      managed care members who are eligible to participate in a disease management (DM)
      program, with some electing to participate while others eschew the opportunity.
      The most pragmatic analytical strategy for in-house evaluation of such programs
      is likely to be the pre-intervention/post-intervention design in which the
      control group consists of people who were invited to participate in the DM
      program, but declined the invitation. Regression estimates of program impacts may
      be statistically biased if factors that impact participation decisions are
      correlated with outcomes measures. This paper describes an econometric procedure,
      the Treatment Effects model, developed to produce statistically unbiased
      estimates of program impacts in this type of situation. Two equations are
      estimated to (a) estimate the impacts of patient characteristics on decisions to
      participate in the program, and then (b) use this information to produce a
      statistically unbiased estimate of the impact of program participation on
      outcomes. This methodology is well-established in economics and econometrics, but
      has not been widely applied in the DM outcomes measurement literature; hence,
      this paper focuses on one illustrative application.

PMID- 15966782
TI  - Primary intensive care: pilot study of a primary care-based intervention for high
      utilizing patients.
AB  - This pilot study was conducted to determine whether primary care patients with
      perceived inappropriate high healthcare utilization would require fewer emergency
      or inpatient services while enrolled in a weekly multidisciplinary clinic.
      Seventeen high-utilizing or difficult management patients of a primary care
      center were referred for the special intervention, Primary Intensive Care (PIC).
      Although not selected for the presence of psychopathology, 16 patients had
      comorbid psychiatric diagnoses. Patients followed in the PIC Clinic had
      significantly lower inpatient and emergency department use during their
      enrollment in the intervention when compared to the matched pre-enrollment time
      period, although the total hospital cost differences did not reach statistical
      significance. Patient and staff satisfaction was high, although the intervention
      was very difficult for the providers.

PMID- 15966783
TI  - Asthma home teaching: two evaluation approaches.
AB  - The aim of this research was to measure the impact of home-based teaching on
      reducing asthma admissions and emergency department (ED) visits for Medicaid
      managed care patients utilizing two different study design methods. This was an
      historical-prospective study utilizing health plan administrative data, including
      membership files and medical claims. We identified 381 patients aged 2-56 with
      hospitalizations or ED visits for asthma. These high risk asthma members were
      recruited for a home-based teaching program to prevent future hospitalizations or
      ED visits. We evaluated program effectiveness using two quasi-experimental
      research designs: a "one-group pre/post-test design," where enrolled members
      served as their own control, and a more rigorous "untreated control group design
      with pre/post test," where results for enrolled members and a similar control
      group were compared pre/post test. Poisson regression models were used to
      investigate the dependence of member rates for asthma-related events on program
      enrollment, age, sex, race, and geographic region. Using the pre/post test
      design, members enrolled in the home-based teaching program demonstrated
      statistically significant reductions in hospital admissions and ED visits (p <
      0.001). The untreated control group design, however, found no association between
      utilization and enrollment in the home-based teaching program (p = 0.510). Small
      differences were detected for subgroups. A marginally statistically significant
      impact of the program was found for Whites, but not for Blacks. The quasi
      experimental design that utilized an external control group provided an approach
      that more accurately explained true disease management program impact. In
      addition, this approach allowed for subgroup analyses to detect opportunities for
      program improvement.

PMID- 15966784
TI  - Technology-driven interactive care management identifies and resolves more
      clinical issues than a claims-based alerting system.
AB  - Due to patient or physician factors, people with chronic diseases frequently do
      not receive evidence-based care. While a physician-directed claims-based alerting
      system targeting gaps in care was previously shown to increase resolution of
      specific clinical issues, many apparently relevant issues remained unresolved.
      The purpose of this research was to demonstrate that adding member interaction
      with a nurse to a physician alerting system can uncover additional care gaps
      beyond those identified by a claims, prescription, and lab results-based alerting
      system, and increase successful resolution of alerts by communicating care gaps
      to members. An opt-in nurse-managed pilot program focusing on identification and
      resolution of specific clinical issues was implemented for 205,463 members of
      self-insured health plans that had been utilizing the claims-based physician
      alerting system. Specific clinical issues identified by the claims-based system
      were communicated to both program enrollees and physicians, and new clinical
      issues were identified based on nurse-directed participant feedback. Participants
      were encouraged to discuss issues with their physicians. Issue resolution rates
      were tracked using subsequent claims, pharmacy, and lab data. At 1 year, we
      studied the rate of new clinical issue identification and compared the program's
      resolution rate of claims-identifiable issues to that of non-enrollees. While
      program participants accounted for 0.65% of total member-months in the pilot
      year, they triggered 4.82% (644) of the population's claims-based clinical
      alerts, and an additional 514 alerts from data based on participant-supplied data
      -80.8% more than claims/pharmacy/lab-generated alerts. Of the participants'
      claims-based alerts, 207 (32.1%) showed claims/lab evidence of successful
      resolution, compared with 3,380 of 12,714 (26.6%) for non-participants, a 20.9%
      increase in resolutions (chi2 = 9.8, p < 0.01). Care management technology
      complemented by a nurse-directed interactive program increased the rate of
      identification of clinical issues compared to claims alerts alone. Use of this
      program to communicate specific issues to both patients and physicians
      significantly increased the rate of issue resolution.

PMID- 15966791
TI  - Protein microarray technology.

PMID- 15966794
TI  - Genomic and proteomic sample preparation: higher throughput solutions. 26-27th
      April, 2004, World Trade Center, Boston, MA, USA.

PMID- 15966795
TI  - Creation of the whole human genome microarray.
AB  - Several companies have recently announced the availability of products that
      enable a scientist to probe gene expression from the entire human genome on a
      single DNA microarray. This review will focus on the underlying technological
      trends that have made this achievement possible, the particular methodologies
      which are employed to create such microarrays and the implications of the whole
      human genome microarray for future biological studies. The single genome array
      represents an important milestone on the path to unraveling the complexity of the
      cellular networks that control living processes. The microarrays being designed
      today may, however, become distant ancestors to the whole human genome arrays of
      the future as our understanding of the functioning of the human genome increases.

PMID- 15966796
TI  - Protein profiling in respiratory disease: techniques and impact.
AB  - Multifactorial diseases such as respiratory disease call for a global analysis of
      such disorders. Recent advances in protein profiling techniques may allow for
      early diagnosis of respiratory disease, which is crucial for intervention and
      treatment. In order to reduce false-positive rates, clinical diagnosis requires a
      high degree of sensitivity and specificity to be an effective screening tool.
      Protein profiles identified by ProteinChip (Ciphergen Biosystems) technology
      coupled with mass spectrometry affords a global analysis of clinical samples and
      is beginning to reach acceptable levels of sensitivity and specificity. Combining
      the profile with another diagnostic tool enhances the effectiveness of protein
      profiles to classify disease. Although current efforts have centered on serum
      protein profiling, the local environment of the lung may be better reflected in
      proteins of bronchoalveolar lavage or sputum. Identification of biomarkers of
      disease by protein profiling analyses may lead to an understanding of the
      mechanisms of this disease and contribute to the discovery of new therapeutics
      for the prevention and treatment of disease. Advancing these analyses are
      techniques such as ProteinChip mass spectrometry, laser capture microdissection,
      tissue microarrays and fluorescently labeled antibody bead arrays, which enable
      the direct global analysis of complex mixtures. Effective high-throughput and
      ease of use of clinical testing will arrive with improvements in bioinformatics
      and decreases in instrumentation costs.

PMID- 15966797
TI  - 2D-LC/MS techniques for the identification of proteins in highly complex
      mixtures.
AB  - Today, 2D online or offline liquid chromatography/mass spectrometry is state of
      the art for the identification of proteins from complex proteome samples in many
      laboratories. Both 2D liquid chromatography methods use two orthogonal liquid
      chromatography separation techniques. The most commonly used techniques are
      strong cation exchange chromatography for the first dimension and reversed phase
      separation for the second dimension. In order to improve sensitivity the reversed
      phase separation is usually performed in the nanoflow scale and mass spectrometry
      is used as the final detection method. The high-performance liquid chromatography
      techniques complement the 2D-gel techniques supporting their weaknesses. This is
      especially true for the gel separation of hydrophobic membrane proteins, which
      play an important role in living cells as well as being important targets for
      future pharmaceutical drugs.

PMID- 15966798
TI  - Role of oncoproteomics in the personalized management of cancer.
AB  - Oncoproteomics is the term used to describe the application of proteomic
      technologies in oncology and parallels the related field of oncogenomics. It is
      now contributing to the development of personalized management of cancer.
      Proteomic technologies are used for the identification of biomarkers in cancer,
      which will facilitate the integration of diagnosis and therapy of cancer.
      Molecular diagnostics, laser capture microdissection and protein biochips are
      among the technologies that are having an important impact on oncoproteomics. The
      discovery of protein patterns developed by the US Food and Drug
      Administration/National Cancer Institute Clinical Proteomics Program is capable
      of distinguishing cancer and disease-free states with high sensitivity and
      specificity and will also facilitate the development of personalized therapy of
      cancer. Examples of application are given for breast and prostate cancer and a
      selection of companies and their collaborations that are developing application
      of proteomics to personalized treatment of cancer are discussed. Continued
      refinement of techniques and methods to determine the abundance and status of
      proteins in vivo holds great promise for the future study of normal cells and the
      pathology of associated neoplasms. Personalized cancer therapy is expected to be
      in the clinic by the end of the first decade of the 21st century.

PMID- 15966799
TI  - Target class strategies in mass spectrometry-based proteomics.
AB  - The cornerstone of proteomics resides in using traditional methods of protein
      chemistry, to extract and resolve complex mixtures, in concert with the powerful
      engines of mass spectrometry to decipher peptide and protein identities. The
      broad utility of proteomics technologies to map protein interactions, understand
      regulatory mechanisms and identify biomarkers associated with disease states and
      drug treatments necessitates a targeted biochemical approach tailored to the
      characteristics of the tissue, fluid or cellular extract being studied. The
      application of affinity methods in proteomic studies to focus on particular
      classes of molecules is being used with increasing frequency and comprises the
      subject of this review. An overview of successfully applied affinity methods is
      provided, along with speculation on the use of innovative approaches. Sample
      preparation and processing are critical for proteomics with affinity reagents, as
      only functional and active proteins can be isolated in most cases. Considerations
      for methods of sample preparation to optimize affinity capture and release are
      also discussed.

PMID- 15966800
TI  - Integrated analysis of genetic, genomic and proteomic data.
AB  - The rapid expansion of methods for measuring biological data ranging from DNA
      sequence variations to mRNA expression and protein abundance presents the
      opportunity to utilize multiple types of information jointly in the study of
      human health and disease. Organisms are complex systems that integrate inputs at
      myriad levels to arrive at an observable phenotype. Therefore, it is essential
      that questions concerning the etiology of phenotypes as complex as common human
      diseases take the systemic nature of biology into account, and integrate the
      information provided by each data type in a manner analogous to the operation of
      the body itself. While limited in scope, the initial forays into the joint
      analysis of multiple data types have yielded interesting results that would not
      have been reached had only one type of data been considered. These early
      successes, along with the aforementioned theoretical appeal of data integration,
      provide impetus for the development of methods for the parallel, high-throughput
      analysis of multiple data types. The idea that the integrated analysis of
      multiple data types will improve the identification of biomarkers of clinical
      endpoints, such as disease susceptibility, is presented as a working hypothesis.

PMID- 15966801
TI  - Using human samples in proteomics-based drug development: bioethical aspects.
AB  - Human samples and related medical data are expected to play an elevated role in
      application-based biomedical proteomics research. Against this framework, some
      facts should be kept in mind by academic and industrial researchers:
      international framework conditions on the use of human samples for research
      purposes are heterogeneous. For example, the value added by the use of human
      samples for product development is significant and the patient's personal and
      property rights may be affected. The body of national laws is growing and these
      laws are binding; guidelines published by international organizations should be
      respected. The most important aspect regards the informed consent of the patient,
      which is addressed in detail.

PMID- 15966802
TI  - High-throughput proteomics using Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - The advent of high-throughput proteomic technologies for global detection and
      quantitation of proteins creates new opportunities and challenges for those
      seeking to gain greater understanding of the cellular machinery. Here, recent
      advances in high-resolution capillary liquid chromatography coupled to Fourier
      transform ion cyclotron resonance mass spectrometry are reviewed along with its
      potential application to high-throughput proteomics. These technological advances
      combined with quantitative stable isotope labeling methodologies provide powerful
      tools for expanding our understanding of biology at the system level.

PMID- 15966803
TI  - Protein structure modeling in the proteomics era.
AB  - Structural proteomics aims to understand the structural basis of protein
      interactions and functions. A prerequisite for this is the availability of 3D
      protein structures that mediate the biochemical interactions. The explosion in
      the number of available gene sequences set the stage for the next step in genome
      scale projects -- to obtain 3D structures for each protein. To achieve this
      ambitious goal, the slow and costly structure determination experiments are
      supplemented with theoretical approaches. The current state and recent advances
      in structure modeling approaches are reviewed here, with special emphasis on
      comparative protein structure modeling techniques.

PMID- 15966804
TI  - What do we learn from high-throughput protein interaction data?
AB  - The biological significance of protein interactions, their method of generation
      and reliability is briefly reviewed. Protein interaction networks adopt a scale
      free topology that explains their error tolerance or vulnerability, depending on
      whether hubs or peripheral proteins are attacked. Networks also allow the
      prediction of protein function from their interaction partners and therefore, the
      formulation of analytical hypotheses. Comparative network analysis predicts
      interactions for distantly related species based on conserved interactions, even
      if sequences are only weakly conserved. Finally, the medical relevance of protein
      interaction analysis is discussed and the necessity for data integration is
      emphasized.

PMID- 15966805
TI  - Proteomics-on-a-chip: the challenge to couple lab-on-a-chip unit operations.
AB  - This review describes a vision of a proteomics-on-a-chip device to separate,
      detect and identify the proteome. It guides the reader towards a development
      strategy, avoiding some of the pitfalls. It also describes the current state-of
      the-art developments in proteomic analysis including available technologies,
      current market issues, the elements of an envisaged proteomics-on-a-chip device,
      the required microfabrication processes and the integration of the elements into
      one device. Address-flow microfluidics is a tool for connecting separation and
      detection platforms. The final section contains an expert opinion on the
      recommended development strategies, benefits of proteomics-on-a-chip in the life
      sciences and the anticipated market.

PMID- 15966806
TI  - Current progress in protein profiling of complex samples.

PMID- 15966807
TI  - Breaking the spell: drug discovery based on modulating protein-protein
      interactions.

PMID- 15966809
TI  - 1st National Congress of the Italian Proteome Society. 27-29th May, 2004,
      Policlinico GB Rossi, Verona, Italy.

PMID- 15966811
TI  - Chemical proteomics from a nuclear magnetic resonance spectroscopy perspective.
AB  - Proteomics is the study of the protein complement of a genome and employs a
      number of newly emerging tools. One such tool is chemical proteomics, which is a
      branch of proteomics devoted to the exploration of protein function using both in
      vitro and in vivo chemical probes. Chemical proteomics aims to define protein
      function and mechanism at the level of directly observed protein-ligand
      interactions, whereas chemical genomics aims to define the biological role of a
      protein using chemical knockouts and observing phenotypic changes. Chemical
      proteomics is therefore traditional mechanistic biochemistry performed in a
      systems-based manner, using either activity- or affinity-based probes that target
      proteins related by chemical reactivities or by binding site shape/properties,
      respectively. Systems are groups of proteins related by metabolic pathway,
      regulatory pathway or binding to the same ligand. Studies can be based on two
      main types of proteome samples: pooled proteins (1 mixture of N proteins) or
      isolated proteins in a given system and studied in parallel (N single protein
      samples). Although the field of chemical proteomics originated with the use of
      covalent labeling strategies such as isotope-coded affinity tagging, it is
      expanding to include chemical probes that bind proteins noncovalently, and to
      include more methods for observing protein-ligand interactions. This review
      presents an emerging role for nuclear magnetic resonance spectroscopy in chemical
      proteomics, both in vitro and in vivo. Applications include: functional
      proteomics using cofactor fingerprinting to assign proteins to gene families;
      gene family-based structural characterizations of protein-ligand complexes; gene
      family-focused design of drug leads; and chemical proteomic probes using nuclear
      magnetic resonance SOLVE and studies of protein-ligand interactions in vivo.

PMID- 15966810
TI  - Characterization and quantitation of membrane proteomes using multidimensional MS
      based proteomic technologies.
AB  - A major goal of proteomics is to develop methods that enable the systematic
      characterization of every protein within the cell or particular subcellular
      proteome using a single analytical platform. Although the equivalent has already
      been achieved in genomics, reaching this goal in proteomics represents a much
      greater challenge due to the wide dynamic range of protein expression, numerous
      post-translational modifications and remarkable physicochemical heterogeneity of
      proteins. A major analytical challenge has involved developing more effective
      means for proteome-scale investigations of membrane proteins, whose solubility
      differs drastically from that of cytoplasmic proteins. Fortunately, rapid
      progress has increased the ability to characterize this critically important
      class of proteins on a scale analogous to that of aqueous soluble proteins.

PMID- 15966812
TI  - Current status of proteomic standards development.
AB  - The generation of proteomic data is becoming ever more high throughput. Both the
      technologies and experimental designs used to generate and analyze data are
      becoming increasingly complex. The need for methods by which such data can be
      accurately described, stored and exchanged between experimenters and data
      repositories has been recognized. Work by the Proteome Standards Initiative of
      the Human Proteome Organization has laid the foundation for the development of
      standards by which experimental design can be described and data exchange
      facilitated. The Minimum Information About a Proteomic Experiment data model
      describes both the scope and purpose of a proteomics experiment and encompasses
      the development of more specific interchange formats such as the mzData model of
      mass spectrometry. The eXtensible Mark-up Language-MI data interchange format,
      which allows exchange of molecular interaction data, has already been published
      and major databases within this field are supplying data downloads in this
      format.

PMID- 15966813
TI  - Novel proteomic approaches for tissue analysis.
AB  - Proteomics, the global study of protein expression and characteristics, has
      recently emerged as a key component in the field of molecular analysis. The
      dynamic nature of proteins, from ion channels to chaperones, presents a
      challenge, yet the understanding of these molecules provides a rich source of
      information. When applying proteomic analysis directly to human tissue samples,
      additional difficulties arise. The following article presents an overview of the
      current proteomic tools used in the analysis of tissues, beginning with
      conventional methods such as western blot analysis and 2D polyacrylamide gel
      electrophoresis. The most current high-throughput techniques being used today are
      also reviewed. These include protein arrays, reverse-phase protein lysate arrays,
      matrix-assisted laser desorption/ionization, surface-enhanced laser
      desorption/ionization and layered expression scanning. In addition,
      bioinformatics as well as issues regarding tissue preservation and
      microdissection to obtain pure cell populations are included. Finally, future
      directions of the tissue proteomics field are discussed.

PMID- 15966814
TI  - Understanding the yeast proteome: a bioinformatics perspective.
AB  - Rapid development of genomic and proteomic methodologies has provided a wealth of
      data for deciphering the biomolecular circuitry of a living cell. The main areas
      of computational research of proteomes outlined in this review are: understanding
      the system, its features and parameters to help plan the experiments; data
      integration, to help produce more reliable data sets; visualization and other
      forms of data representation to simplify interpretation; modeling of the
      functional regulation; and systems biology. With false-positive rates reaching
      50% even in the more reliable data sets, handling the experimental error remains
      one of the most challenging tasks. Integrative approaches, incorporating results
      of various genome- and proteome-wide experiments, allow for minimizing the error
      and bring with them significant predictive power.

PMID- 15966815
TI  - Techniques for studying protein heterogeneity and post-translational
      modifications.
AB  - Proteins often undergo several post-translational modification steps in parallel
      to protein folding. These modifications can be transient or of a more permanent
      nature. Most modifications are, however, susceptible to alteration during the
      lifespan of proteins. Post-translational modifications thus generate variability
      in proteins that are far beyond that provided by the genetic code. Co- and post
      translational modifications can convert the 20 specific codon-encoded amino acids
      into more than 100 variant amino acids with new properties. These, and a number
      of other modifications, can considerably increase the information content and
      functional repertoire of proteins, thus making their analysis of paramount
      importance for diagnostic and basic research purposes. Various methods used in
      proteomics, such as 2D gel electrophoresis, 2D liquid chromatography, mass
      spectrometry, affinity-based analytical methods, interaction analyses, ligand
      blotting techniques, protein crystallography and structure-function predictions,
      are all applicable for the analysis of these numerous secondary modifications. In
      this review, examples of some of these techniques in studying the heterogeneity
      of proteins are highlighted. In the future, these methods will become
      increasingly useful in biomarker searches and in clinical diagnostics.

PMID- 15966816
TI  - Targeted proteomics using immunoblotting technique for studying dysregulation of
      ion transporters in renal disorders.
AB  - Renal salt and water transport physiology has benefited tremendously from the
      rapid advance of proteomics. Proteomics developed as a fast-throughput means of
      screening for global changes in proteins in a selected tissue, organ or cell
      type, as a logical offshoot of similar comprehensive, messenger RNA array-type
      technology. Targeted proteomics utilizes similar techniques but examines a
      predetermined set of proteins. One approach that has been rigorously employed
      over the last 10 years to evaluate differences in renal protein abundances due to
      a treatment or genotype has been parallel semiquantitative immunoblotting using
      antibody arrays. This approach, and newer ones on the horizon, provide a rapid
      global overview of regulation of the individual proteins whose integrated action
      determines overall renal sodium or water reabsorption.

PMID- 15966817
TI  - Review of uses of network and graph theory concepts within proteomics.
AB  - The size and nature of data collected on gene and protein interactions has led to
      a rapid growth of interest in graph theory and modern techniques for describing,
      characterizing and comparing networks. Simultaneously, this is a field of growth
      within mathematics and theoretical physics, where the global properties, and
      emergent behavior of networks, as a function of the local properties has long
      been studied. In this review, a number of approaches for exploiting modern
      network theory to help describe and analyze different data sets and problems
      associated with proteomic data are considered. This review aims to help
      biologists find their way towards useful ideas and references, yet may also help
      scientists from a mathematics and physics background to understand where they may
      apply their expertise.

PMID- 15966818
TI  - Protein interaction networks.
AB  - The study of protein interactions is playing an ever increasing role in our
      attempts to understand cells and diseases on a system-wide level. This article
      reviews several experimental approaches that are currently being used to measure
      protein-protein, protein-DNA and gene-gene interactions. These techniques have
      now been scaled up to produce extensive genome-wide data sets that are providing
      us with a first glimpse of global interaction networks. Complementing these
      experimental approaches, several computational methodologies to predict protein
      interactions are also reviewed. Existing databases that serve as repositories for
      protein interaction information and how such databases are used to analyze high
      throughput data from a pathway perspective is also addressed. Finally, current
      efforts to combine multiple data types to obtain more accurate and comprehensive
      models of protein interactions are discussed. It is clear that the evolution of
      these experimental and computational approaches is rapidly changing our view of
      biology, and promises to provide us with an unprecedented ability to model cells
      and organisms at a system-wide level.

PMID- 15966819
TI  - Nanocrystallography: an emerging technology for structural proteomics.

PMID- 15966822
TI  - British Society for Proteome Research. 12-13th July, 2004, European
      Bioinformatics Institute, Hinxton, UK.

PMID- 15966823
TI  - New approaches towards integrated proteomic databases and depositories.
AB  - Since the publication of the human genome, two key points have emerged. First, it
      is still not certain which regions of the genome code for proteins. Second, the
      number of discrete protein-coding genes is far fewer than the number of different
      proteins. Proteomics has the potential to address some of these postgenomic
      issues if the obstacles that we face can be overcome in our efforts to combine
      proteomic and genomic data. There are many challenges associated with high
      throughput and high-output proteomic technologies. Consequently, for proteomics
      to continue at its current growth rate, new approaches must be developed to ease
      data management and data mining. Initiatives have been launched to develop
      standard data formats for exchanging mass spectrometry proteomic data, including
      the Proteomics Standards Initiative formed by the Human Proteome Organization.
      Databases such as SwissProt and Uniprot are publicly available repositories for
      protein sequences annotated for function, subcellular location and known
      potential post-translational modifications. The availability of bioinformatics
      solutions is crucial for proteomics technologies to fulfil their promise of
      adding further definition to the functional output of the human genome. The aim
      of the Oxford Genome Anatomy Project is to provide a framework for integrating
      molecular, cellular, phenotypic and clinical information with experimental
      genetic and proteomics data. This perspective also discusses models to make the
      Oxford Genome Anatomy Project accessible and beneficial for academic and
      commercial research and development.

PMID- 15966824
TI  - Principles and applications of multidimensional protein identification
      technology.
AB  - Multidimensional chromatography coupled to tandem mass spectrometry is an
      emerging technique for the analysis of proteomes and is rapidly being implemented
      by many researchers for proteomic analysis. In this technology profile, a
      particular proteomic approach known as multidimensional protein identification
      technology (MudPIT) is discussed. In MudPIT, a biphasic microcapillary column is
      packed with high-performance liquid chromatography grade reversed phase and
      strong cation exchange packing materials, loaded with a complex peptide mixture
      and placed in line with quaternary high-performance liquid chromatography and a
      tandem mass spectrometer. MudPIT has the capability to analyze highly complex
      proteomic mixtures such as whole proteomes, organelles and protein complexes.

PMID- 15966825
TI  - Tissue microarrays: fast-tracking protein expression at the cellular level.
AB  - Tissue microarrays maximize returns in cellular pathology whilst minimizing the
      use of cells and tissues. They are made by arraying cores of tissue taken from
      multiple donor blocks into a single recipient block. Accordingly, the histology
      and pathology of several hundred tissues can be represented in one tissue
      microarray that, when stained by immunohistochemistry, provides comprehensive
      topographic information on protein expression. Used with complimentary
      techniques, such as complementary DNA microarray analysis, tissue microarrays are
      providing valuable data for the identification of new markers of disease and
      assisting in the discovery of therapeutic targets. They are also leading a
      revolution in cellular pathology as high-throughput technology is introduced to
      maximize the information provided.

PMID- 15966826
TI  - Large-scale proteomic analysis of membrane proteins.
AB  - Proteomic analysis of membrane proteins is a promising approach for the
      identification of novel drug targets and/or disease biomarkers. Despite notable
      technological developments, obstacles related to extraction and solublization of
      membrane proteins are encountered. A critical discussion of the different
      preparative methods of membrane proteins is offered in relation to downstream
      proteomic applications, mainly gel-based analyses and mass spectrometry.
      Frequently, unknown proteins are identified by high-throughput profiling of
      membrane proteins. In search for novel membrane proteins, analysis of protein
      sequences using computational tools is performed to predict the presence of
      transmembrane domains. This review also presents these bioinformatic tools with
      the human proteome as a case study. Along with technological innovations,
      advancements in the areas of sample preparation and computational prediction of
      membrane proteins will lead to exciting discoveries.

PMID- 15966827
TI  - Kinase selectivity profiling by inhibitor affinity chromatography.
AB  - As new drugs rapidly advance into clinical trials, comprehensive identification
      of their intracellular targets becomes fundamental for the full understanding of
      the molecular basis of their efficacy and toxicity. This is particularly
      important when the targets belong to a large family and the inhibitors recognize
      a conserved site among different members of the class. A typical example is the
      kinase family, where efforts are aimed at the development of inhibitors of
      distinct kinases for therapeutic applications in oncology, inflammation and other
      disease areas. In this case, inhibitors targeting the ATP pocket may cross react
      with different kinases, as well as with other proteins that bind ATP. This review
      critically discusses the available approaches for kinase selectivity profiling.
      It also reviews some examples of inhibitor affinity chromatography applied to
      inhibitors of kinases and other protein families as a tool to identify and
      characterize their intracellular targets.

PMID- 15966828
TI  - Mass spectrometry-based quantitative proteomics.
AB  - A major aim of present-day proteomics is to study changes in protein expression
      levels at a global level, ideally monitoring all proteins present in cells or
      tissue. Mass spectrometry is a well-respected technology in proteomics that is
      widely used for the identification of proteins. More recently, methodologies have
      been introduced showing that mass spectrometry can also be used for protein
      quantification. This article reviews various mass spectrometry-based technologies
      in quantitative proteomics, highlighting several interesting applications in
      areas ranging from cell biology to clinical applications.

PMID- 15966829
TI  - Quantitative methods for the analysis of protein phosphorylation in drug
      development.
AB  - Most signal transduction and cell signaling pathways are mediated by protein
      kinases. Protein kinases have emerged as important cellular regulatory proteins
      in many aspects of neoplasia. Protein kinase inhibitors offer the opportunity to
      target diseases such as cancer with chemotherapeutic agents specific for the
      causative molecular defect. In order to identify possible targets and assess
      kinase inhibitors, quantitative methods for analyzing protein phosphorylation
      have been developed. This review examines some of the current formats used for
      quantifying kinase function for drug development.

PMID- 15966830
TI  - Proteomic analysis of cellular signaling.
AB  - Protein phosphorylation events are key regulators of cellular signaling
      processes. In the era of functional genomics, rational drug design programs
      demand large-scale high-throughput analysis of signal transduction cascades.
      Significant improvements in the area of mass spectrometry-based proteomics have
      provided exciting opportunities for rapid progress toward global protein
      phosphorylation analysis. This review summarizes several recent advances made in
      the field of phosphoproteomics with an emphasis placed on mass spectrometry
      instrumentation, enrichment methods and quantification strategies. In the near
      future, these technologies will provide a tool that can be used for quantitative
      investigation of signal transduction pathways to generate new insights into
      biologic systems.

PMID- 15966831
TI  - High-throughput proteomics using antibody microarrays.
AB  - Antibody-based microarrays are a novel technology that hold great promise in
      proteomics. Microarrays can be printed with thousands of recombinant antibodies
      carrying the desired specificities, the biologic sample (e.g., an entire
      proteome) and any specifically bound analytes detected. The microarray patterns
      that are generated can then be converted into proteomic maps, or molecular
      fingerprints, revealing the composition of the proteome. Using this tool, global
      proteome analysis and protein expression profiling will thus provide new
      opportunities for biomarker discovery, drug target identification and disease
      diagnostics, as well as providing insights into disease biology. Intense work is
      currently underway to develop this novel technology platform into the high
      throughput proteomic tool required by the research community.

PMID- 15966832
TI  - Redox proteomics: identification and functional role of glutathionylated
      proteins.
AB  - Although radical oxygen and nitrogen species are harmful molecules that destroy
      cell functions, many operate as mediators of important cell signaling pathways
      when not in excess. Oxidants can modify protein function through the covalent,
      reversible addition of glutathione to cysteine. This review addresses different
      proteomic methods of identifying glutathionylation targets and emphasizes ways of
      defining their pattern of modification in response to oxidative stimuli in cells.
      Finally, the literature on nonproteomic studies that investigate the functional
      changes induced by glutathionylation are reviewed and future studies are
      commented on.

PMID- 15966833
TI  - The Coomassie chronicles: past, present and future perspectives in polyacrylamide
      gel staining.

PMID- 15966835
TI  - 1st Workshop for Human Diseases Glycomics/Proteome Initiative of HUPO. 23-24th
      August, 2004, Senri Life Science Center, Osaka, Japan.

PMID- 15966836
TI  - 15th meeting on Methods in Protein Structure Analysis. 29th August-2nd September,
      2004, University of Washington, WA, USA.

PMID- 15966837
TI  - All about DIGE: quantification technology for differential-display 2D-gel
      proteomics.
AB  - 2D polyacrylamide gel electrophoresis has been the traditional workhorse of
      proteomics, allowing for the resolution of several thousand proteins in a single
      gel. Difference gel electrophoresis is an emerging technology that allows for
      accurate quantification with statistical confidence while controlling for
      nonbiologic variation, and also increases the dynamic range and sensitivity of
      traditional 2D polyacrylamide gel electrophoresis. With inclusion of an internal
      standard formed from equal amounts of every sample in an experiment, difference
      gel electrophoresis technology also allows for repetitive measurements and
      multivariable analyses to be quantitatively analyzed in one co-ordinated
      experiment, yielding statistically-significant changes in protein expression
      related to many disease states. This technique promises to be an important tool
      in clinical proteomics and the study of the mechanism of disease, investigating
      diagnostic biomarkers and pinpointing novel therapeutic targets.

PMID- 15966838
TI  - Depletion and fractionation technologies in plasma proteomic analysis.
AB  - This review intends to survey the traditional and current technologies in the
      depletion and subfractionation of plasma proteins for further analyses. The value
      of depletion aims to enrich low-abundant proteins by removing highly abundant
      proteins, such as albumin or immunoglobulin G, from plasma. With this approach,
      one can examine both the resulting high- and low-abundant protein fractions. The
      depleted protein population can be further subfractionated based on their
      isoelectric point ranges, creating a more discrete pool of proteins for detailed
      post-translational modification studies by methods such as 2D gel electrophoresis
      and mass spectrometry. The concept of divide to conquer will greatly enhance our
      ability to identify and characterize low-abundant proteins and cleaved peptides
      from plasma as important diagnostic markers or potential drug targets. This can
      potentially reverse the decline in the development of new plasma diagnostic
      tests.

PMID- 15966839
TI  - Isotope-differentiated binding energy shift tags (IDBEST) for improved targeted
      biomarker discovery and validation.
AB  - Mass spectrometry has proved to be an important tool for protein biomarker
      discovery, identification and characterization. However, global proteomic
      profiling strategies often fail to identify known low-abundance biomarkers as a
      result of the limited dynamic range of mass spectrometry (two to three orders of
      magnitude) compared with the large dynamic range of protein concentrations in
      biologic fluids (11 to 12 orders of magnitude for serum). In addition, the number
      of peptides generated in such methods vastly overwhelms the resolution capacity
      of mass spectrometers, requiring extensive sample clean-up (e.g., affinity tag,
      retentate chromatography and/or high-performance liquid chromatography) before
      mass spectrometry analysis. Baiting and affinity pre-enrichment strategies, which
      overcome the dynamic range and sample complexity issues of global proteomic
      strategies, are very difficult to couple to mass spectrometry. This is due to the
      fact that it is nearly impossible to sort target peptides from those of the bait
      since there will be many cases of isobaric peptides. IDBEST (Target Discovery,
      Inc.) is a new tagging strategy that enables such pre-enrichment of specific
      proteins or protein classes as the resulting tagged peptides are distinguishable
      from those of the bait by a mass defect shift of approximately 0.1 atomic mass
      units. The special characteristics of these tags allow: resolution of tagged
      peptides from untagged peptides through incorporation of a mass defect element;
      high-precision quantitation of up- and downregulation by using stable isotope
      versions of the same tag; and potential analysis of protein isoforms through more
      complete peptide coverage from the proteins of interest.

PMID- 15966840
TI  - Mass spectrometric approaches for characterizing bacterial proteomes.
AB  - The emergence of advanced liquid chromatography mass spectrometry technologies
      for characterizing very complex mixtures of proteins has greatly propelled the
      field of proteomics, the goal of which is the simultaneous examination of all the
      proteins expressed by an organism. This research area represents a paradigm shift
      in molecular biology by attempting to provide a top-down qualitative and
      quantitative view of all the proteins (including their modifications and
      interactions) that are essential for an organism's life cycle, rather than
      targeting a particular protein family. This level of global protein information
      about an organism such as a bacterium can be combined with genomic and
      metabolomic data to enable a systems biology approach for understanding how these
      organisms live and function.

PMID- 15966841
TI  - Chip-based nanoelectrospray mass spectrometry for protein characterization.
AB  - In the last several years, significant progress has been made in the development
      of microfluidic-based analytical technologies for proteomic and drug discovery
      applications. Chip-based nanoelectrospray coupled to a mass spectrometer detector
      is one of the recently developed analytical microscale technologies. This
      technology offers unique advantages for automated nanoelectrospray including
      reduced sample consumption, improved detection sensitivity and enhanced data
      quality for proteomic studies. This review presents an overview and introduction
      of recent developments in chip devices coupled to electrospray mass spectrometers
      including the development of the automated nanoelectrospray ionization chip
      device for protein characterization. Applications using automated chip-based
      nanoelectrospray ionization technology in proteomic and bioanalytical studies are
      also extensively reviewed in the fields of high-throughput protein
      identification, protein post-translational modification studies, top-down
      proteomics, biomarker screening by pattern recognition, noncovalent protein
      ligand binding for drug discovery and lipid analysis. Additionally, future trends
      in chip-based nanoelectrospray technology are discussed.

PMID- 15966842
TI  - Bioinformatics in mass spectrometry data analysis for proteomics studies.
AB  - Mass spectrometry is a technique widely employed for the identification and
      characterization of proteins. The role of bioinformatics is fundamental for the
      elaboration of mass spectrometry data due to the amount of data that this
      technique can produce. To process data efficiently, new software packages and
      algorithms are continuously being developed to improve protein identification and
      characterization in terms of high-throughput and statistical accuracy. However,
      many limitations exist concerning bioinformatics spectral data elaboration. This
      review aims to critically cover the recent and future developments of new
      bioinformatics approaches in mass spectrometry data analysis for proteomics
      studies.

PMID- 15966843
TI  - What can proteomic analyses contribute to understanding the molecular biology and
      clinical behavior of prostate cancer?
AB  - Identifying the proteins and their complex interactions that promote and/or
      sustain the aggressive malignant phenotype is essential for understanding key
      effectors of the molecular biology of prostate cancer. This is also essential for
      development of new clinical applications. A variety of proteomic techniques,
      ranging from mass spectrometry to new methods of multiplexing protein
      identification, have great potential for rapidly achieving these goals. However,
      in order to obtain meaningful results, these techniques must be applied within
      the context of our knowledge of the heterogeneity of prostate tissues and tumors,
      the impact of specimen processing on both the quality and quantity of proteins
      detected and a thorough understanding of prostate cell biology. Collaboration
      between the protein chemist and the prostate cell biologist will expedite
      progress in this important field.

PMID- 15966844
TI  - Proteomic technologies and their application to pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma is a devastating disease that represents an
      important health problem. It spreads rapidly at a time when patients have
      relatively few symptoms and consequently is often only detected at an advanced
      stage when treatment options are limited. Rapid developments in technology and
      bioinformatics have recently led to a surge in proteomics-based cancer research.
      Comparative analysis of protein profiles from nonmalignant and malignant pancreas
      cells or tissue, or from different stages of pancreatic cancer, potentially offer
      unique insight into the biology of this tumor type. Furthermore, proteomic
      approaches may provide novel diagnostic or therapeutic markers for this disease.
      Although such analyses are still in their infancy, they show great potential in
      the ongoing battle against this dismal disease.

PMID- 15966845
TI  - Absolute quantification strategies in proteomics based on mass spectrometry.
AB  - The strong need for quantitative information in proteomics has fueled the
      development of mass spectrometry-based analytical methods that are able to
      determine protein abundances. This article reviews mass spectrometry experiments
      aimed at providing an absolute quantification of proteins. The experiments make
      use of the isotope-dilution concept by spiking a known amount of synthetic,
      isotope-labeled reference peptide into the analyte sample. Quantification is
      achieved by comparing the mass spectrometry signal intensities of the reference
      with an endogenous peptide that is generated upon proteolytic cleavage of the
      target protein. In an analogous manner, the level of post-translational
      modification at a distinct residue within a target protein can be determined.
      Among the strengths of absolute quantification are low detection limits reaching
      subfemtomole levels, a high dynamic range spanning approximately five orders of
      magnitude, low requirements for sample clean-up, and a fast and straightforward
      method development. Recent studies have demonstrated the compatibility of
      absolute quantification with various mass spectrometry readout techniques and
      sample purification steps such as 1D gel electrophoresis, size-exclusion
      chromatography, isoelectric peptide focusing, strong cation exchange and reversed
      phase or affinity chromatography. Under ideal conditions, quantification errors
      and coefficients of variation below 5% have been reported. However, the fact that
      at the start of the experiment the analyte is a protein and the internal standard
      is a peptide, severe quantification errors may result due to the selection of
      unsuitable reference peptides and/or imperfect protein proteolysis. Within the
      ensemble of mass spectrometry-based quantification methods, absolute
      quantification is the method of choice in cases where absolute numbers, many
      repetitive experiments or precise levels of post-translational modifications are
      required for a few, preselected species of interest. Consequently, prominent
      application areas include biomarker quantification, the study of post
      translational modifications such as phosphorylation or ubiquitination and the
      comparison of concentrations of interacting proteins.

PMID- 15966846
TI  - HUPO Brain Proteome Project: aims and needs in proteomics.

PMID- 15966848
TI  - HUPO 3rd annual World Congress on Proteomics. 25-27th October, 2004, Beijing,
      China.

PMID- 15966849
TI  - Protein microarrays as a discovery tool for studying protein-protein
      interactions.
AB  - Exploring the function of the genome and the encoded proteins has emerged as a
      new and exciting challenge in the postgenomic era. Novel technologies come into
      view that promise to be valuable for the investigation not only of single
      proteins, but of entire protein networks. Protein microarrays are the innovative
      assay platform for highly parallel in vitro studies of protein-protein
      interactions. Due to their flexibility and multiplexing capacity, protein
      microarrays benefit basic research, diagnosis and biomedicine. This review
      provides an overview on the basic principles of protein microarrays and their
      potential to multiplex protein-protein interaction studies.

PMID- 15966850
TI  - Multidimensional protein identification technology: current status and future
      prospects.
AB  - Protein profiling using high-throughput tandem mass spectrometry has become a
      powerful method for analyzing changes in global protein expression patterns in
      cells and tissues as a function of developmental, physiologic and disease
      processes. This review summarizes the utility and practical application of
      multidimensional protein identification technology as a platform for
      comprehensive proteomic profiling of complex biologic samples. The strengths and
      potential problems and limitations associated with this powerful technology are
      discussed, with an emphasis placed on one of the biggest challenges currently
      facing large-scale expression profiling projects -- namely, data analysis.
      Complementary bioinformatic computational data mining strategies, such as
      clustering, functional annotation and statistical inference, are also discussed
      as these are increasingly necessary for interpreting the results of global
      proteomic profiling studies.

PMID- 15966851
TI  - Diagnostic and analytical applications of protein microarrays.
AB  - DNA microarrays have changed the field of biomedical sciences over the past 10
      years. For several reasons, antibody and other protein microarrays have not
      developed at the same rate. However, protein and antibody arrays have emerged as
      a powerful tool to complement DNA microarrays during the past 5 years. A genome
      scale protein microarray has been demonstrated for identifying protein-protein
      interactions as well as for rapid identification of protein binding to a
      particular drug. Furthermore, protein microarrays have been shown as an efficient
      tool in cancer profiling, detection of bacteria and toxins, identification of
      allergen reactivity and autoantibodies. They have also demonstrated the ability
      to measure the absolute concentration of small molecules. Besides their capacity
      for parallel diagnostics, microarrays can be more sensitive than traditional
      methods such as enzyme-linked immunosorbent assay, mass spectrometry or high
      performance liquid chromatography-based assays. However, for protein and antibody
      arrays to be successfully introduced into diagnostics, the biochemistry of
      immunomicroarrays must be better characterized and simplified, they must be
      validated in a clinical setting and be amenable to automation or integrated into
      easy-to-use systems, such as micrototal analysis systems or point-of-care
      devices.

PMID- 15966852
TI  - High-throughput automated platform for nuclear magnetic resonance-based
      structural proteomics.
AB  - The development of new systems and strategies capable of synthesizing any desired
      soluble, labeled protein or protein fragment on a preparative scale is one of the
      most important tasks in biotechnology today. The Center for Eukaryotic Structural
      Genomics (WI, USA), in co-operation with Ehime University (Matsuyama, Japan) and
      CellFree Sciences Co., Ltd, has developed an automated platform for nuclear
      magnetic resonance-based structural proteomics that employs wheat germ extracts
      for cell-free production of labeled protein. The platform utilizes a single
      construct for all targets without any redesign of the DNA or RNA. Therefore, it
      offers advantages over commercial cell-free methods utilizing Escherichia coli
      extracts that require multiple constructs or redesign of the open reading frame.
      The protein production and labeling protocol is no more costly than E. coli cell
      based approaches, is robust and scalable for high-throughput applications. This
      protocol has been used in the authors center to screen eukaryotic open reading
      frames from the Arabidopsis thaliana and human genomes and for the determination
      of nuclear magnetic resonance structures. With the recent addition of the
      GeneDecoder 1000 (CellFree Sciences Co., Ltd) robotic system, the Center for
      Eukaryotic Structural Genomics is able to carry out as many as 384 small-scale
      (50 microl) screening reactions per week. Furthermore, the Protemist (CellFree
      Sciences Co., Ltd) robotic system enables the Center for Eukaryotic Structural
      Genomics to carry out 16 production-scale (4 ml) reactions per week. Utilization
      of this automated platform technology to screen targets for expression and
      solubility and to produce stable isotope-labeled samples for nuclear magnetic
      resonance structure determinations is discussed.

PMID- 15966853
TI  - CSF proteome: a protein repository for potential biomarker identification.
AB  - Proteomic analysis is not limited to the analysis of serum or tissues. Synovial,
      peritoneal, pericardial and cerebrospinal fluid represent unique proteomes for
      disease diagnosis and prognosis. In particular, cerebrospinal fluid serves as a
      rich source of putative biomarkers that are not solely limited to neurologic
      disorders. Peptides, proteolytic fragments and antibodies are capable of crossing
      the blood-brain barrier, thus providing a repository of pathologic information.
      Proteomic technologies such as immunoblotting, isoelectric focusing, 2D gel
      electrophoresis and mass spectrometry have proven useful for deciphering this
      unique proteome. Cerebrospinal fluid proteins are generally less abundant than
      their corresponding serum counterparts, necessitating the development and use of
      sensitive analytical techniques. This review highlights some of the promising
      areas of cerebrospinal fluid proteomic research and their clinical applications.

PMID- 15966854
TI  - Potential of proteomics towards the investigation of the IGF-independent actions
      of IGFBP-3.
AB  - Early investigations into the insulin-like growth factor (IGF)-independent
      actions of insulin-like growth factor-binding protein (IGFBP)-3 have implicated a
      large array of signaling proteins with links to cell cycle control and apoptosis.
      However, the actual mechanism of IGFBP-3 action is still unclear. In an effort to
      clearly understand the mechanism of IGF-independent IGFBP-3 actions, a proteomic
      approach to identify the actual proteins involved in interaction with IGFBP-3
      from different cell compartments, the phosphorylation status of IGFBP-3 under
      different physiologic conditions and the proteins upregulated by IGFBP-3 are
      briefly reviewed. The IGF system is a well-recognized key player in diseases such
      as cancer, diabetes and malnutrition. It is only after the signaling pathways of
      the IGF-independent actions of IGFBP-3 are clearly understood that the system can
      be manipulated to affect these disorders.

PMID- 15966855
TI  - Proteomic analysis of glycosylation: structural determination of N- and O-linked
      glycans by mass spectrometry.
AB  - This review summarizes the methods, mainly based on mass spectrometry, for the
      structural determination of N- and O-linked carbohydrates that are post
      translationally attached to a large number of proteins and which play a key role
      in determining the function and biophysical properties of these compounds.
      Analysis of these carbohydrates has proved difficult in the past due to their
      structural complexity. However, modern analytical methods such as mass
      spectrometry have the ability to elucidate most structural details at the
      concentration levels required for proteomics. This review describes methods for
      direct examination of glycoproteins by mass spectrometry, the release of N- and O
      linked glycans from glycoproteins separated in sodium dodecyl sulfate
      polyacrylamide electrophoresis gels, and the analysis of these compounds by
      techniques such as matrix-assisted laser desorption/ionization and electrospray
      ionization mass spectrometry. Matrix-assisted laser desorption/ionization mass
      spectrometry provides the most rapid method for comparing glycan profiles and is
      probably most appropriate for clinical studies. One of the most promising
      techniques for determining the structures of N-glycans in proteomic studies is
      negative ion fragmentation of electrosprayed ions. This technique combines high
      throughput with ease of structural interpretation and provides structural details
      that are difficult to obtain by classical methods.

PMID- 15966856
TI  - Understanding signal transduction through functional proteomics.
AB  - The study of signal transduction provides fundamental information regarding the
      regulation of all biologic processes that support the normal function of life.
      Functional proteomics, a rapidly emerging discipline that aims to understand the
      expression, function and regulation of the entire set of proteins in a given cell
      type, tissue or organism, offers unprecedented opportunity for signal
      transduction research in terms of understanding cellular behavior and regulation
      at the systems level. Indeed, swift progress in the area of proteomics has
      demonstrated the major impact of proteomic approaches on signal transduction and
      biomedical research. In this review, recent and innovative applications of
      functional proteomics in determining changes in protein contents, modifications,
      activities and interactions underpinning signaling transduction pathways are
      discussed.

PMID- 15966857
TI  - Phosphoproteomics in analyzing signaling pathways.
AB  - A surprisingly fewer than expected number of genes in the human genome suggests
      that sophistication of its biologic system is, in part, due to complex regulation
      of protein activities. The activities of most cellular proteins are regulated by
      post-translational modifications. One of the most important post-translational
      modifications is reversible protein phosphorylation, which decorates more than
      30% of the proteome and regulates signal transduction pathways under normal
      conditions as well as in disorders such as diabetes, neurodegenerative diseases,
      autoimmune diseases and several forms of cancers. This review examines the recent
      developments in mass spectrometry-based methods for phosphoproteome analysis and
      its applications for the study of signal transduction pathways. The basic
      principles of non-mass spectrometry-based methods, such as chemical genetics and
      flow cytometry-based approaches, are also discussed as well as their specific
      advantages to signaling studies. Finally, signaling pathways are discussed in the
      light of large-scale protein interaction studies. The proteomic methods addressed
      in this review are emerging as some of the essential components in systems
      biology, which seeks to describe signaling networks through integration of
      diverse types of data and, in the future, to allow computational simulations of
      complex biologic pathways in health and disease.

PMID- 15966858
TI  - Computational characterization of proteins.
AB  - Computational characterization of proteins is a necessary first step in
      understanding the biologic role of a protein. The composite architecture of
      mammalian proteins makes the prediction of the biologic role rather difficult.
      Nevertheless, integration of many different prediction methods allows for a more
      accurate representation. Information on the 3D structure of a protein improves
      the reliability of predictions of many features. This article reviews existing
      methods used to characterize proteins and several tools that provide an
      integrated access to different types of information. The authors point out the
      increasing importance of structural constraints and an increasing need to
      integrate different approaches.

PMID- 15966859
TI  - Enrichment of low-molecular-weight proteins from biofluids for biomarker
      discovery.
AB  - The dramatic progress in mass spectrometry-based methods of protein
      identification has triggered a new quest for disease-associated biomarkers.
      Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and
      its variant surface-enhanced laser desorption/ionization mass spectrometry,
      provide effective means to explore the less studied information slice of the
      human serum proteome -- low-molecular-weight proteins and peptides. These low
      molecular-weight proteins and peptides are promising for the detection of
      important biomarkers. Due to the significant experimental problems imposed by
      high-abundance and high-molecular-weight proteins, it is important to effectively
      remove these species prior to mass spectrometry analysis of the low-molecular
      weight serum and plasma proteomes. In this review, the advantages afforded by
      recently introduced methods for prefractionation of serum, as they pertain to the
      detection and identification of biomarkers, will be discussed.

PMID- 15966860
TI  - A TrkA-to-p75NTR molecular switch activates amyloid beta-peptide generation
      during aging.
AB  - Aging is the single most important risk factor for AD (Alzheimer's disease).
      However, the molecular events that connect normal aging to AD are mostly unknown.
      The abnormal accumulation of Abeta (amyloid beta-peptide) in the form of senile
      plaques is one of the main characteristics of AD. In the present study, we show
      that two members of the neurotrophin receptor superfamily, TrkA (tyrosine kinase
      receptor A) and p75NTR (p75 neurotrophin receptor), differentially regulate the
      processing of APP (amyloid precursor protein): TrkA reduces, whereas p75NTR
      activates, beta-cleavage of APP. The p75NTR-dependent effect requires NGF (nerve
      growth factor) binding and activation of the second messenger ceramide. We also
      show that normal aging activates Abeta generation in the brain by 'switching'
      from the TrkA to the p75NTR receptor system. Such an effect is abolished in
      p75NTR 'knockout' animals, and can be blocked by both caloric restriction and
      inhibitors of nSMase (neutral sphingomyelinase). In contrast with caloric
      restriction, which prevents the age-associated up-regulation of p75NTR
      expression, nSMase inhibitors block the activation of ceramide. When taken
      together, these results indicate that the p75NTR-ceramide signalling pathway
      activates the rate of Abeta generation in an age-dependent fashion, and provide a
      new target for both the understanding and the prevention of late-onset AD.

PMID- 15966861
TI  - A method for filling in the cohesive ends of double-stranded DNA using Pfu DNA
      polymerase.
AB  - The present paper reports a highly efficient method of making blunt ends from
      cohesive ends of double-stranded DNA. Klenow fragment and Pfu DNA polymerases
      were used to fill in the cohesive ends. Since the transformation efficiency can
      directly reflect the filling-in efficiency, similar ligation and transformation
      conditions were used, and the filling-in efficiency was compared with the
      corresponding transformation efficiency. The results indicate that the filling-in
      efficiency of Pfu DNA polymerase was 1.96 times that of Klenow fragment and its
      efficiency was markedly higher than that of Klenow fragment (P<0.01). The
      optimization experiments on reaction conditions indicate, when the pH is 8.5 and
      the temperature is 74 degrees C, that the filling-in efficiency was highest upon
      using a buffer containing 3 mM MgSO4 and 300 microM dNTP.

PMID- 15966862
TI  - H-NS is a part of a thermally controlled mechanism for bacterial gene regulation.
AB  - Temperature is a primary environmental stress to which micro-organisms must be
      able to adapt and respond rapidly. Whereas some bacteria are restricted to
      specific niches and have limited abilities to survive changes in their
      environment, others, such as members of the Enterobacteriaceae, can withstand
      wide fluctuations in temperature. In addition to regulating cellular physiology,
      pathogenic bacteria use temperature as a cue for activating virulence gene
      expression. This work confirms that the nucleoid-associated protein H-NS (histone
      like nucleoid structuring protein) is an essential component in thermoregulation
      of Salmonella. On increasing the temperature from 25 to 37 degrees C, more than
      200 genes from Salmonella enterica serovar Typhimurium showed H-NS-dependent up
      regulation. The thermal activation of gene expression is extremely rapid and
      change in temperature affects the DNA-binding properties of H-NS. The reduction
      in gene repression brought about by the increase in temperature is concomitant
      with a conformational change in the protein, resulting in the decrease in size of
      high-order oligomers and the appearance of increasing concentrations of discrete
      dimers of H-NS. The present study addresses one of the key complex mechanisms by
      which H-NS regulates gene expression.

PMID- 15966863
TI  - Aquaporin-3 functions as a glycerol transporter in mammalian skin.
AB  - The AQPs (aquaporins) are a family of homologous water transporting proteins
      expressed in many mammalian epithelial, endothelial and other cell types.
      Phenotype analysis of mice lacking individual AQPs has been informative in
      elucidating their role in mammalian physiology. For example, phenotype analysis
      has indicated an important role of AQPs in the renal urinary concentrating
      mechanism (AQP1-AQP4), brain water balance and neural signal transduction (AQP4),
      exocrine gland secretion (AQP5) and ocular fluid balance (AQP1, AQP5). In skin,
      the aquaglyceroporin AQP3 is expressed in the basal layer of epidermal
      keratinocytes. Mice deficient in AQP3 have dry skin with reduced SC (stratum
      corneum) hydration, decreased elasticity and impaired biosynthesis. Mechanistic
      analysis of the altered skin phenotype in AQP3 deficiency suggested that the
      glycerol rather than the water transporting function of AQP3 is important in skin
      physiology. The glycerol content of SC and epidermis of AQP3 deficient mice is
      reduced, whereas that of dermis and serum is normal. The dry, relatively
      inelastic skin in AQP3 null mice is probably related to the humectant properties
      of glycerol, and the impaired SC repair to impaired epidermal biosynthetic
      function. The key role of AQP3 in epidermal physiology might be exploited in the
      development of improved cosmetics and new therapies for skin diseases associated
      with altered skin water content.

PMID- 15966864
TI  - Aquaporins in yeasts and filamentous fungi.
AB  - Recently, genome sequences from different fungi have become available. This
      information reveals that yeasts and filamentous fungi possess up to five
      aquaporins. Functional analyses have mainly been performed in budding yeast,
      Saccharomyces cerevisiae, which has two orthodox aquaporins and two
      aquaglyceroporins. Whereas Aqy1 is a spore-specific water channel, Aqy2 is only
      expressed in proliferating cells and controlled by osmotic signals. Fungal
      aquaglyceroporins often have long, poorly conserved terminal extensions and
      differ in the otherwise highly conserved NPA motifs, being NPX and NXA
      respectively. Three subgroups can be distinguished. Fps1-like proteins seem to be
      restricted to yeasts. Fps1, the osmogated glycerol export channel in S.
      cerevisiae, plays a central role in osmoregulation and determination of
      intracellular glycerol levels. Sequences important for gating have been
      identified within its termini. Another type of aquaglyceroporin, resembling S.
      cerevisiae Yfl054, has a long N-terminal extension and its physiological role is
      currently unknown. The third group of aquaglyceroporins, only found in
      filamentous fungi, have extensions of variable size. Taken together, yeasts and
      filamentous fungi are a fruitful resource to study the function, evolution, role
      and regulation of aquaporins, and the possibility to compare orthologous
      sequences from a large number of different organisms facilitates functional and
      structural studies.

PMID- 15966865
TI  - Imaging phosphoinositide dynamics using GFP-tagged protein domains.
AB  - Phosphoinositides are important regulators of cellular homoeostasis and numerous
      signal-transduction pathways. One of their major features is their ability to
      recruit signalling proteins to membranes by direct interaction with
      phosphoinositide-binding modules. The distribution and dynamics of membrane
      phosphoinositides are therefore major determinants in the spatiotemporal control
      of cell signalling and membrane trafficking. However, standard biochemical
      approaches cannot reveal the dynamics of phosphoinositides at the single-cell
      level. A major technical advance has been the development of genetically encoded
      fluorescent phosphoinositide probes on the basis of the phosphoinositide-binding
      domains found in signalling proteins, such as the PH (pleckstrin homology)
      domain. This review describes the diverse fluorescent phosphoinositide probes
      available for imaging specific phosphoinositide species and how their use has
      improved the understanding of phosphoinositide signalling at the single-cell
      level.

PMID- 15966866
TI  - Linkage of genetics and ethics: more crossing over is needed.
AB  - Since the development of recombinant DNA technology in the mid 1970s, there has
      been increasing interest in the ethical, legal, and social implications of
      genetics and related fields. The web sites of five different organizations
      (government, academic, and independent not-for-profit) that deal explicitly with
      genetics and ethics are reviewed here. Some of the sites cover genetics and other
      issues in bioethics while others cover human genetics exclusively. The target
      audiences for the sites include medical and scientific professionals, students,
      and the general public. Among the issues examined are genetic testing, genetic
      discrimination in employment and health insurance, genetically modified foods,
      stem cells and DNA patenting. Resources for those interested in legal issues are
      particularly well-represented on these sites.

PMID- 15966867
TI  - Fetal and perinatal programming of appetite.
AB  - There is increasing concern about the rapidly rising incidence of obesity
      worldwide and its impact both on mortality, morbidity and the cost of healthcare.
      In the last 15 years, a large volume of research has linked low birth weight to
      many adult diseases in humans, such as Type II diabetes, cardiovascular disease,
      hypertension and the metabolic syndrome. Obesity is a causal factor in all these
      conditions. There are epidemiological studies linking low birth weight to
      increased adiposity, but the timing of the insult during gestation seems crucial,
      as reducing maternal nutrition in late gestation and during lactation causes a
      reduction in later obesity. Recent studies in animal models have provided clues
      towards mechanisms of altered appetite regulation following alterations in fetal
      and neonatal growth. The outcome of these and future studies could prove
      clinically crucial, particularly in the debate over the benefits of breast
      feeding, which provides a lower plane of nutrition compared with formula feeding.

PMID- 15966868
TI  - Chronic myeloid leukaemia: stem cell derived but progenitor cell driven.
AB  - The biology of CML (chronic myeloid leukaemia) has been extensively investigated
      as the disease is a paradigm of neoplasms induced when a translocation results in
      expression of a novel fusion protein, in this instance p210(BCR-ABL). Although
      CML manifests itself principally as unregulated expansion of the myeloid lineage,
      the lesion is present in the stem cell population and it has long been assumed
      that disregulated stem cell kinetics must underlie the basic pathology of the
      disease. In this review, we present evidence that, in normal haemopoiesis, less
      primitive precursor cells retain considerable flexibility in their capacity to
      undergo self-renewal, allowing them to maintain lineage-specific homoeostasis
      without inflicting proliferative stress upon the stem cell population. This
      mechanism is dysregulated in CML and we have developed a self-renewal assay for
      CFU-GM (colony-forming unit-granulocyte/macrophage) which demonstrates that, in
      CML, the PI (proliferative index) of the myeloid progenitor cell population is
      increased. The ability to measure the PI as an endpoint of p210(BCR-ABL)
      expression gives considerable versatility to the in vitro investigation of
      putative therapeutic regimes in CML.

PMID- 15966869
TI  - Therapeutic uses of autologous endothelial cells for vascular disease.
AB  - Endothelial cells play important structural and functional roles in vascular
      homoeostasis. Perturbations in endothelial cell number and function are directly
      involved with the initiation and progression of multiple cardiovascular diseases,
      including atherosclerosis, hypertension and congestive heart failure. Attempts to
      modify these disorders have included pharmacological strategies to improve
      vascular and thus endothelial function. A goal of biological approaches to these
      disorders is the delivery of endothelial cells that might act to provide
      beneficial endothelial-derived factors. However, this approach has generally been
      limited by the lack of readily available autologous endothelial cells for
      delivery. The isolation of circulation-derived endothelial progenitor cells
      allows for direct access to autologous endothelial cells for preclinical and
      clinical studies. Preclinical studies using autologous endothelial cells have
      demonstrated beneficial effects when delivered in animal models of vascular
      injury and grafting. These effects are related to the endothelial nature of the
      cells and may be paracrine in nature. Ongoing studies are aimed at defining the
      nature of these effects and optimizing delivery strategies cognizant of these
      mechanisms.

PMID- 15966870
TI  - Suppression of the pro-apoptotic function of cytochrome c by singlet oxygen via a
      haem redox state-independent mechanism.
AB  - Stimuli for apoptotic signalling typically induce release of cyt c (cytochrome c)
      from mitochondria. Cyt c then initiates the formation of the apoptosome,
      comprising Apaf-1 (apoptotic protease-activating factor 1), caspase-9 and other
      cofactors. The issue of whether the redox state of the haem in cyt c affects the
      initiation of the apoptotic pathway is currently a subject of debate. In a cell
      free reconstitution system, we found that only oxidized cyt c was capable of
      activating the caspase cascade. Oxidized cyt c was reduced by the physiological
      reductants cysteine and glutathione, after which it was unable to activate the
      caspase cascade. It is thus likely that cyt c with oxidized haem is in a
      conformation capable of interaction with Apaf-1 and forming apoptosomes. When
      either oxidized or reduced cyt c was treated with submillimolar concentrations of
      endoperoxide, which affected less than 3% of the redox state of haem, the ability
      of the oxidized cyt c to activate the caspase cascade was abolished. Higher
      amounts of singlet oxygen were required to affect the optical spectral change of
      haem, suggesting that the suppressed pro-apoptotic function of oxidized cyt c is
      a mechanism that is separate from the redox state of haem. Oxidative protein
      modification of cyt c by singlet oxygen was evident, on the basis of elevated
      contents of carbonyl compounds. Our data suggest that singlet oxygen eliminates
      the pro-apoptotic ability of oxidized cyt c not via the reduction of haem, but
      via the modification of amino acid residues that are required for apoptosome
      formation.

PMID- 15966871
TI  - Mn2+-adenosine nucleotide complexes in the presence of the nitrogenase iron
      protein: detection of conformational rearrangements directly at the nucleotide
      binding site by EPR and 2D-ESEEM (two-dimensional electron spin-echo envelope
      modulation spectroscopy).
AB  - Both ATP and a bivalent nucleotide-bound metal activator, normally Mg2+, are
      required for nitrogenase activity. EPR and ESEEM (electron spin-echo envelope
      modulation) measurements have been carried out on adenosine nucleotides in which
      the Mg2+ ion that is usually bound is replaced by Mn2+ in the presence of Kp2
      (nitrogenase Fe-protein from Klebsiella pneumoniae). The Mn2+ zero-field
      splitting parameters have been determined from the EPR-spectrum to be |D|=0.0125
      cm(-1) with a rhombicity lambda=E/D=0.31 by direct diagonalization of the
      complete spin Hamiltonian. ESEEM spectra of the Fe-protein with MnADP and MnATP
      both show an ESEEM line pair with one signal component at about 3.6 MHz and a
      relatively broad resonance at 8 MHz originating from a superhyperfine coupling to
      a 31P nuclear spin from one or more directly co-ordinated phospho group(s) of the
      nucleotide. A pronounced resonance overlapping the low-frequency component of the
      (31)P-signal at about 3.5 MHz is attributed to an interaction of Mn2+ with
      univalent 23Na nuclei. ESEEM lines at frequencies <3.5 MHz have been ascribed to
      interactions with 14N nuclei. Differences in the 14N features that depend on the
      type of nucleotide are consistent with substantial conformational rearrangements
      at the nucleotide-binding site upon hydrolysis. In addition, four-pulse HYSCORE
      (hyperfine sublevel correlation spectroscopy) experiments not only confirm the
      three-pulse ESEEM results, but also achieve significantly better spectral
      deconvolution, especially of the 31P-couplings, and demonstrate that the
      nucleotide is at least a unidentate ligand of Mn2+. Moreover it was also possible
      to identify peaks from an 14N interaction more clearly; these most probably arise
      from outer-sphere interactions with nitrogen atom(s) of non-co-ordinated residues
      which are affected by conformational rearrangements upon nucleotide hydrolysis.
      In addition, different redox states of the [4Fe-4S] cluster of the Fe-protein
      show disparate conformations of the metal-nucleotide co-ordination environment,
      demonstrating that also the cluster site communicates with the nucleotide binding
      site.

PMID- 15966872
TI  - Clinical attachment loss produced by curettes and ultrasonic scalers.
AB  - OBJECTIVES: The aim of this study was to clinically detect the immediate effect
      of root instrumentation with curettes and ultrasonic scalers on clinical
      attachment level. MATERIAL AND METHODS: Twelve subjects with moderate chronic
      periodontitis, presenting probing depths of 3.5-6.5 mm on anterior teeth, upper
      and/or lower, were selected. Teeth were randomly assigned to one of the following
      groups: US group--scaled with an ultrasonic scaler; and CC group--scaled and
      planed with 5-6 Gracey curettes. The selected teeth were probed with a
      computerized electronic probe, guided by an occlusal stent and subjected to
      scaling and root planing. Immediately following instrumentation, teeth were
      probed again. The difference between relative attachment level (RAL) immediately
      before and after instrumentation was considered trauma from instrumentation.
      RESULTS: Intra-group analysis revealed statistically significant differences
      between RAL immediately before and after instrumentation in both groups (0.77+/
      0.51 for US group; and 0.73+/-0.41 for CC group, p<0.0001). However, inter-group
      analysis did not show statistically significant difference in trauma from
      instrumentation caused by the two different instruments (p=0.816). CONCLUSIONS:
      Within the limits of this study, it was concluded that root instrumentation
      causes a mean immediate attachment loss of 0.75 mm, and that instrumentation with
      either curettes or ultrasonic scalers do not seem to reduce significantly the
      trauma from of instrumentation produced.

PMID- 15966873
TI  - Predictive value of clinical and microbiological parameters for the treatment
      outcome of scaling and root planing.
AB  - OBJECTIVES: To compare the clinical and microbiological outcome of non-surgical
      periodontal therapy after 6 months with data obtained after hygienic phase or 6
      weeks after completion of non-surgical therapy, in order to evaluate the value of
      clinical and microbiological parameters to predict treatment success. MATERIAL
      AND METHODS: Clinical and microbiological data were available from 271 sites in
      10 systemically healthy non-smokers with moderate-to-advanced chronic periodontal
      disease (24-32 sites per individual). Subgingival plaque samples were tested for
      the presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans,
      Tannerella forsythensis and Treponema denticola using RNA probes. RESULTS:
      Stepwise multiple linear regression analysis revealed a significant impact of the
      number of sites with visible plaque index >1 after hygienic phase on the bleeding
      tendency of a subject at month 6 (p<0.01). Furthermore, an association could be
      demonstrated between the number of residual pockets (PD>3 mm) 6 months after
      therapy and the number of bleeding sites and suppurating sites after hygienic
      phase (p=0.016). Six weeks after therapy, the mean total bacterial loads had a
      significant impact on the bleeding tendency of a subject at month 6 (p<0.01).
      Although the average numbers of sites with persisting P. gingivalis, A.
      actinomycetemcomitans, T. forsythensis and T. denticola seemed to be very similar
      6 weeks and 6 months after therapy, large variations were noted between subjects,
      and therefore the microbiological status of a subject at week 6 could not predict
      the status at month 6. CONCLUSIONS: The present study showed a limited potential
      of microbiological tests, performed after hygienic phase or shortly after non
      surgical periodontal therapy, to predict the clinical outcome 6 months later, but
      confirmed the importance of an establishment of perfect oral hygiene before non
      surgical therapy.

PMID- 15966874
TI  - The relationship between emotional intelligence and initial response to a
      standardized periodontal treatment: a pilot study.
AB  - OBJECTIVES: Emotional intelligence (EI) is a psychological construct, which has
      been proposed as a measure of coping mechanisms. The aim of this pilot study was
      to investigate the relationship between different domains of EI, and initial
      response to a simplified non-surgical treatment protocol in 29 patients with
      chronic periodontitis. METHODS: Assessment of patients included socio-demographic
      and behavioural variables and assessment of EI. Clinical assessment included
      measurement of plaque and gingival bleeding. Patients received oral hygiene
      instruction (OHI) and supra-gingival scaling and polishing over two visits, and
      re-assessed after 3 weeks. RESULTS: There was a significant overall reduction in
      plaque and bleeding. Plaque reduction was positively associated with the EI
      construct of intentionality, resilience, constructive discontent and personal
      power (Spearman's rank test). Reduction in bleeding was positively correlated
      with resilience, constructive discontent and intuition. CONCLUSIONS: This pilot
      study demonstrated an association between EI domains and short-term changes in
      plaque and bleeding, and suggest that initial responses to standardized
      periodontal treatment may be partly related to EI.

PMID- 15966875
TI  - Bacteraemia following periodontal procedures.
AB  - INTRODUCTION: Transient bacteraemias are frequently detected following dental
      manipulation. Infective endocarditis (IE) can arise in susceptible individuals
      and antibiotic prophylaxis is routinely performed for certain procedures
      considered to be "at risk" of IE. Evidence is emerging that periodontal disease
      may be a significant risk factor for the development of certain systemic diseases
      such as cardiovascular disease. These systemic conditions could be initiated or
      detrimentally influenced by the repeated entry of bacteria into the bloodstream.
      MATERIALS AND METHODS: The present study comprised a single blind parallel study
      of 2 weeks duration. A baseline blood sample was obtained from 30 volunteers with
      untreated periodontal disease following which a periodontal probing depth chart
      was collected. A further blood sample was taken following this procedure, and
      each subject was recalled 2 weeks later. A blood sample was collected, the
      subject carried out toothbrushing and a further blood sample taken. Full-mouth
      ultrasonic scaling was then performed and a final blood sample taken. Blood
      samples were analysed for bacteraemia using conventional microbiological culture
      and polymerase chain reaction (PCR) using universal bacterial primers that target
      the 16S ribosomal RNA gene of the vast majority of bacteria. RESULTS: Using
      culture methods, the incidence of bacteraemias was as follows: following
      ultrasonic scaling (13%), periodontal probing (20%) and toothbrushing (3%). PCR
      analysis revealed bacteraemia incidences following ultrasonic scaling,
      periodontal probing and toothbrushing of 23%, 16% and 13%, respectively.
      CONCLUSION: These findings suggest that detectable dental bacteraemias induced by
      periodontal procedures are at a lower level than previously reported.

PMID- 15966876
TI  - The short-term effects of low-level lasers as adjunct therapy in the treatment of
      periodontal inflammation.
AB  - OBJECTIVES: The aim of this split-mouth, double-blind controlled clinical trial
      was to study the effects of irradiation with low-level lasers as an adjunctive
      treatment of inflamed gingival tissue. MATERIALS AND METHODS: Seventeen patients
      with moderate periodontitis were included. After clinical examination, all teeth
      were scaled and root planed (SRP). One week after SRP, we took samples of
      gingival crevicular fluid (GCF) and subgingival plaque. The laser therapy was
      started 1 week later and continued once a week for 6 weeks. One side of the upper
      jaw was treated with active laser and the other with a placebo. The test side was
      treated with two low-level lasers having wavelengths of 635 and 830 nm. The
      patients then underwent another clinical examination with sampling of GCF and
      plaque. The GCF samples were analysed for elastase activity, interleukin-1beta
      (IL-1beta) and metalloproteinase-8 (MMP-8). We examined the subgingival plaque
      for 12 bacteria using DNA probes. RESULTS: The clinical variables i.e. probing
      pocket depth, plaque and gingival indices were reduced more on the laser side
      than on the placebo one (p<0.01). The decrease in GCF volume was also greater on
      the laser side, 0, 12 microl, than on the placebo side, 0.05 microl (p=0.01). The
      total amount of MMP-8 increased on the placebo side but was slightly lower on the
      laser side (p=0.052). Elastase activity, IL-1beta concentration and the
      microbiological analyses showed no significant differences between the laser and
      placebo sides. CONCLUSION: Additional treatment with low-level lasers reduced
      periodontal gingival inflammation.

PMID- 15966877
TI  - Healing of intra-bony defects following treatment with a composite bovine-derived
      xenograft (Bio-Oss Collagen) in combination with a collagen membrane (Bio-Gide
      PERIO).
AB  - AIM: The purpose of the present study was to compare clinically the treatment of
      deep intra-bony defects with a combination of a composite bovine-derived
      xenograft (BDX Coll) and a bioresorbable collagen membrane [guided tissue
      regeneration (GTR)] to access flap surgery only. METHODS: Thirty-two patients,
      each of whom displayed one intra-bony defect, were treated either with BDX
      Coll+GTR (test) or with access flap surgery (control). The results were evaluated
      at 1 year following therapy. RESULTS: No differences in any of the investigated
      parameters were observed at baseline between the two groups. Healing was
      uneventful in all patients. At 1 year after therapy, the test group showed a
      reduction in the mean probing depth (PD) from 8.3+/-1.5 to 2.9+/-1.3 mm (p<0.001)
      and a change in the mean clinical attachment level (CAL) from 9.4+/-1.3 to 5.3+/
      1.5 mm (p<0.0001). In the control group, the mean PD was reduced from 8.0+/-1.2
      to 4.4+/-1.7 mm (p<0.001) and the mean CAL changed from 9.6+/-1.3 to 7.9+/-1.6 mm
      (p<0.01). The test treatment resulted in statistically higher PD reductions (p<
      or =0.05) and CAL gains (p<0.001) than the control one. In the test group, all
      sites (100%) gained at least 3 mm of CAL. In this group, a CAL gain of 3 or 4 mm
      was measured at 10 sites (62%), whereas at six sites (38%), the CAL gain was 5 or
      6 mm. In the control group, no CAL gain occurred at three sites (19%), whereas at
      10 sites (62%), the CAL gain was only 1 or 2 mm. A CAL gain of 3 mm was measured
      in three defects (19%). CONCLUSIONS: Within the limits of the present study, it
      can be concluded that the combination of BDX Coll+GTR resulted in significantly
      higher CAL gains than treatment with access flap surgery alone, and thus appears
      to be a suitable alternative for treating intra-bony periodontal defects.

PMID- 15966878
TI  - A regimen of systematic periodontal care after removal of impacted mandibular
      third molars manages periodontal pockets associated with the mandibular second
      molars.
AB  - AIM: This randomized, single-blinded control trial investigated the local effects
      of periodontal care on the mandibular second molar delivered during and after
      impacted third molar surgical extraction. METHOD: Thirty subjects (50% male,
      32.1+/-7.8 years) out of 35 enrolled, with a mesio-angular impacted mandibular
      third molar, having probing pocket depth (PPD) >5 mm at adjacent second molar
      distal, and crestal radio-lucency between the two teeth, completed the study.
      Oral hygiene instruction, scaling and caries stabilization were performed before
      surgery. Controls (n=16) had their third molar extracted followed by standard
      socket debridement. Test group subjects (n=14) received the same treatment,
      except that before wound closure the operator was informed of the group
      allocation and ultrasonic root debridement on the second molar was performed,
      followed by a three-visit plaque control programme. RESULTS: Six months post
      extraction, statistically significantly (p<0.007) better plaque control and
      shallower probing depths were observed at test second molars' distal (%plaque=21;
      PPD=3.2+/-1.2 mm) than at control second molars (%plaque=88; PPD=5.2+/-0.7 mm).
      CONCLUSIONS: The periodontal interventions investigated prevented residual
      pockets on periodontally involved second molars 6 months after ipsilateral
      impacted mandibular third molar removal.

PMID- 15966879
TI  - Single-visit, full-mouth ultrasonic debridement: a paradigm shift in periodontal
      therapy?

PMID- 15966880
TI  - Effects of single-visit full-mouth ultrasonic debridement versus quadrant-wise
      ultrasonic debridement.
AB  - BACKGROUND: The aim of this randomized controlled clinical trial was to determine
      the effects of single-visit full-mouth ultrasonic debridement versus quadrant
      wise therapy. MATERIAL AND METHODS: Thirty-six subjects with chronic
      periodontitis, were randomly allocated to three groups--quadrant-wise ultrasonic
      debridement, single-visit full-mouth ultrasonic debridement with povidone iodine
      and single-visit full-mouth ultrasonic debridement with water. Whole-mouth
      plaque, bleeding on probing (BOP), pocket depth and attachment level were
      recorded before treatment and 1, 3 and 6 months post-treatment. Plaque and saliva
      samples were collected for microbiological analysis. RESULTS: After treatment,
      all groups showed significant improvement in clinical parameters. Full-mouth
      treatments resulted in similar improvements in full-mouth mean plaque percentage,
      probing pocket depth and probing attachment level as conventional therapy. When
      data were analysed based on pocket depth and tooth type, there was no difference
      between groups in probing depth reduction or attachment gains. The full-mouth
      groups demonstrated greater reduction in BOP% and number of pockets > or =5 mm
      and the total treatment time was significantly shorter. The detection frequencies
      of periodontal pathogens in plaque and saliva showed slight changes with no
      difference between groups. CONCLUSION: Single-visit full-mouth mechanical
      debridement may have limited additional benefits over quadrant-wise therapy in
      the treatment of periodontitis, but can be completed in a shorter time.

PMID- 15966881
TI  - Re-treatment profiles during long-term maintenance therapy in a periodontal
      practice in Norway.
AB  - BACKGROUND: Periodontal therapy coupled with active maintenance has been shown to
      be effective in maintaining periodontal health, however, the question of re
      treatment is rarely alluded to in the literature. AIM: To quantify the type and
      extent of re-treatment in a group of patients who had completed a definitive
      course of periodontal treatment in a Norwegian specialist periodontal practice.
      The study also investigated factors associated with the provision of periodontal
      surgery as a re-treatment modality. METHODS: A consecutive group of patients who
      had comprehensive periodontal treatment, which included periodontal surgery, and
      were subsequently maintained for between 10 and 17 years were studied. RESULTS:
      One hundred and one patients with an average age at reassessment of 59.4
      (standard deviation (SD) 9.0) years were studied. The average length of the
      review period was 13.1 (SD 1.9) years. In addition to routine maintenance, 50
      patients had further re-treatment and 40 of those who were re-treated had
      periodontal surgery in the study period. Logistic regression showed that
      independent predictors of surgical re-treatment, with the effects adjusted for
      other variables in the model, were uncertain or poor prognosis at baseline,
      erratic or poor post baseline compliance and a family history of periodontal
      disease. CONCLUSION: Considerable amounts of re-treatment, including in many
      cases extensive non-surgical treatment or periodontal surgery, were provided for
      patients who had surgical periodontal treatment and were subsequently maintained
      for least 10 years in a specialist periodontal practice.

PMID- 15966882
TI  - A chlorhexidine varnish implemented treatment strategy for chronic periodontitis:
      short-term clinical observations.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical outcome of a
      subgingivally applied chlorhexidine varnish when used as an adjunct to scaling
      and root planing (SRP) in the treatment of chronic periodontitis. MATERIAL AND
      METHODS: A randomized controlled, single blind, parallel trial was conducted on
      the basis of 16 volunteers suffering from chronic periodontitis. The control
      group received oral hygiene instructions and was scaled and root planed in two
      sessions. The test group received the same instructions and treatment, however,
      all pockets were additionally disinfected using a chlorhexidine varnish. The
      gingival index, plaque index, bleeding on probing, probing pocket depth (PPD) and
      clinical attachment level (CAL) were recorded at baseline and subsequently after
      1 and 3 months. RESULTS: Both treatment strategies showed significant reductions
      in PPD and CAL at both follow-up visits by comparison with baseline levels
      (p<0.001). Yet, at study termination, combination therapy resulted in additional
      pocket reductions between 0.73 and 1.23 mm (p<0.02), and clinical attachment
      gains between 0.63 and 1.09 mm (p<0.02). CONCLUSIONS: These findings suggest that
      a varnish-implemented strategy may improve the clinical outcome for the treatment
      of chronic periodontitis in comparison with SRP alone.

PMID- 15966883
TI  - The effect of a dentifrice and mouth rinse combination containing amine
      fluoride/stannous fluoride on plaque and gingivitis: a 6-month field study.
AB  - AIM: To examine the effect of amine fluoride/stannous fluoride (AmF/SnF(2))
      containing dentifrice and mouth rinse on plaque formation and gingivitis as
      compared with habitual oral hygiene procedures with a regular sodium fluoride
      (NaF) dentifrice. MATERIAL AND METHODS: In total, 22 general practices
      participated in this research project. The participants (N=281) were randomly
      assigned into two groups: the test group received an AmF/SnF(2) dentifrice-mouth
      rinse combination and the control group received a NaF-containing dentifrice. The
      patients were requested to brush twice daily for approximately 2 min. The
      subjects of the test group had to rinse additionally in the evening for 30 s with
      10 ml of the mouth rinse. RESULTS: Both groups started with comparable scores of
      plaque, bleeding and staining. At 6 months, the plaque scores were 0.95 for the
      AmF/SnF(2) group and 0.99 for the NaF group (decrease of 16% and 10%,
      respectively). Bleeding scores, although significantly different from baseline,
      did not show differences between the two regimes. At the end of the experimental
      period, the overall staining was more pronounced in the AmF/SnF(2) group (41%)
      than the NaF group (26%). Both plaque reduction and increase in staining seemed
      to be correlated to the amount of mouth rinse used in the test group. CONCLUSION:
      In instruction-resistant patients recruited from dental practices, the combined
      use of AmF/SnF(2) did not decrease gingivitis at a significant level in
      comparison with the regular regime of two times daily brushing with an NaF
      containing dentifrice. However, the above-mentioned combination resulted in
      greater plaque reduction than that observed with the use of the conventional
      dentifrice. When used according to the manufacturer's instructions, this effect
      on plaque scores was more pronounced.

PMID- 15966884
TI  - The combined use of enamel matrix proteins and a tetracycline-coated expanded
      polytetrafluoroethylene barrier membrane in the treatment of intra-osseous
      defects.
AB  - OBJECTIVES: The purpose of this split-mouth study was to evaluate the clinical
      response of enamel matrix proteins (EMPs, Emdogain Gel in intra-osseous defects
      with or without a combined application of a tetracycline-coated expanded
      polytetrafluoroethylene barrier membrane (e-PTFE, Gore-Tex). METHODS: Twelve
      pairs of intra-osseous periodontal defects in 11 patients received the
      application of EMPs on the exposed root surface (EMP). One of the two defects
      received randomly, as an adjunct to EMP treatment, a tetracycline-coated e-PTFE
      membrane (MEMP). At baseline, 6- and 12-month probing pocket depth (PPD),
      clinical attachment level (CAL) and probing bone level (PBL) were measured.
      RESULTS: After 12 months, the EMP defects showed a significant mean PPD reduction
      of 2.86+/-0.75 mm, a mean gain in CAL of 1.28+/-2.04 mm, a mean PBL gain of
      1.63+/-1.21 mm and a mean increase of recession (REC) of 1.56+/-2.30 mm. The MEMP
      defects showed a significant mean PPD reduction of 3.02+/-1.55 mm, a mean gain in
      CAL of 1.65+/-1.29 mm, a mean PBL gain of 1.58+/-1.92 mm and a mean increase of
      REC of 1.38+/-1.63 mm. Except for significantly more post-operative discomfort at
      the MEMP sites, no significant differences were found between EMP and MEMP
      defects. CONCLUSION: Within the limits of this study, it is concluded that in the
      treatment of intra-osseous defects with EMP, the adjunctive use of a tetracycline
      coated e-PTFE membrane failed to show more gain of CAL and PBL.

PMID- 15966885
TI  - In vitro studies of a degradable device for controlled-release of meloxicam.
AB  - BACKGROUND: Plaque biofilm and associated host responses are the primary factors
      in the pathogenesis of periodontitis. Delivery of medications directly into the
      periodontal pockets to suppress or eradicate the pathogenic microbiota or
      modulate the inflammatory response has attracted significant interest to limit
      periodontal tissue destruction. The aim of the present study was twofold: (1) to
      describe the development of a biodegradable controlled-release device containing
      meloxicam as the therapeutic agent and (2) to evaluate the in vitro release of
      meloxicam from this device into different release media. METHODS: Films of cross
      linked gelatin matrix containing meloxicam were prepared, hardened for various
      time periods and cut in a form to fit to the periodontal pocket anatomy. The
      release of active agents was studied separately in 10 ml distilled water,
      artificial saliva and pH 7.4 phosphate buffer at 37 degrees C. Apparatus Vibrax
      was used at 120 r.p.m. Determinations were carried out spectrophotometrically,
      and the release profiles were plotted as a function of time. The results were
      evaluated by the similarity test. RESULTS: The release rates of meloxicam from
      the hardened (1 h, 4 h, 8 h) formulations were slower than the unhardened
      formulation in all the three release media. Increasing the hardening time
      decreased the release rates. The overall release rates were similar in artificial
      saliva and pH 7.4 phosphate buffer, while it was lower in distilled water.
      CONCLUSIONS: As a conclusion, cross-linked gelatin matrix films may be considered
      as a suitable inert material for obtaining a prolonged local release of meloxicam
      as an adjunct to the mechanical periodontal treatment. As required, further in
      vitro and in vivo studies will be performed before starting clinical applications
      of this controlled-release formulation of the anti-inflammatory agent.

PMID- 15966886
TI  - Comparison of culture and real-time PCR for detection and quantification of five
      putative periodontopathogenic bacteria in subgingival plaque samples.
AB  - OBJECTIVES: Bacterial cultivation is a well-established method for analyzing
      plaque samples. Real-time polymerase chain reaction (PCR) is a novel rapid method
      for the identification and quantification of periodontopathogenic bacteria that
      has been recently introduced. In this study, we compared real-time PCR with
      conventional anaerobic cultivation. METHOD: A total of 78 subgingival plaque
      samples were harvested from pockets > or =5 mm in 22 patients with advanced
      chronic periodontitis and immediately transferred into transport medium. Aliquots
      were evaluated with species-specific probes by real-time PCR (meridol Perio
      Diagnostics, GABA) and anaerobic bacteria culture on selective media for the
      detection of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum,
      Porphyromonas gingivalis, Prevotella intermedia and Tannerella forsythensis. The
      analysis was performed by two separate, blinded examiners. RESULTS: When real
      time PCR was compared with the culture method (golden standard) for the detection
      of putative periodontopathogenic bacteria, the sensitivity and specificity for A.
      actinomycetemcomitans were 67% and 100%, respectively (kappa: 0.79); for F.
      nucleatum 73% and 53%, respectively (kappa: 0.21); for P. gingivalis 94% and 84%,
      respectively (kappa: 0.77); for P. intermedia 33% and 94%, respectively (kappa:
      0.26) and for T. forsythensis 92% and 56%, respectively (kappa: 0.51). Spearman's
      correlation coefficients for the quantitative results of both methods were 0.82
      for A. actinomycetemcomitans, 0.33 for F. nucleatum, 0.83 for P. gingivalis, 0.38
      for P. intermedia and 0.67 for T. forsythensis. CONCLUSION: Overall, the
      agreement between both test methods was excellent for A. actinomycetemcomitans
      and P. gingivalis, fair for T. forsythensis and poor for F. nucleatum and P.
      intermedia. The discrepancies in the results may be explained by the inability of
      cultivation methods to distinguish between close related taxa, and the problems
      of keeping periopathogenic bacteria viable, which is required for standard
      cultivation.

PMID- 15966887
TI  - Reducing variability and choosing ideal subjects for experimental gingivitis
      studies.
AB  - INTRODUCTION: This study was undertaken to test the hypothesis that male, non
      smokers, aged 25-50 years, with a proven track record of developing gingivitis
      would provide suitable subjects for experimental gingivitis studies because the
      inter-subject variation would be greatly reduced. MATERIALS AND METHODS: Subjects
      were required to be men aged between 25 and 50 years, in good general health with
      at least four sound teeth in one posterior quadrant of the mandible. Subjects who
      were smokers, taking antibiotics, anti-inflammatory drugs or had any other
      medical, surgical or social condition making participation in the study
      inadvisable, were excluded. Subjects had previously participated in a 21-day
      experimental gingivitis study. Subjects with the most gingivitis at the end of
      the previous study were invited to participate first, moving down the list until
      the required number of subjects had been achieved. Subjects were randomly
      assigned to one of three toothpastes: Crest Gum Care, Mentadent P or a placebo
      (UK Signal). Subjects were asked to brush their teeth twice daily for 1 min.,
      with the tooth-shield in place and containing 1 ml of their assigned toothpaste.
      RESULTS: Thirty-five subjects completed the study using the placebo, 36 used
      Mentadent P and 39 completed the study using Crest Gum Care. Both toothpastes
      containing active gum health ingredients (Triclosan and Zinc Citrate in Mentadent
      P and Stannous Fluoride in Crest Gum Care) resulted in statistically significant
      reductions in gingival bleeding and inflammation. Although a directional
      reduction, there was no statistically significant reduction in plaque scores. No
      significant differences between the two active groups were established.
      CONCLUSION: The factors that were controlled or measured and analyzed in these
      studies were: gender, smoking status, age and chronic gingivitis level. The
      results add support to the hypothesis that male subjects show less variation,
      however there is limited evidence linking the female menstrual cycles to
      variations in gingivitis status. Further research in this area is required before
      definitive conclusions can be made. Selecting a subject population in order to
      decrease variation must be undertaken with caution. A subject population selected
      for particular attributes can be extremely valuable when assessing the anti
      gingivitis potential of new agents, but this population would be as biased if
      used for large efficacy clinical trials. The data obtained will not necessarily
      be able to be generalized, that is, applicable to the whole population. However
      there is sufficient evidence to justify balancing for (or excluding) smokers from
      subject populations in experimental gingivitis studies.

PMID- 15966888
TI  - Long-term effect of smoking on vertical periodontal bone loss.
AB  - OBJECTIVES: The objective of the present study was to investigate the influence
      of smoking on vertical periodontal bone loss over 10 years. MATERIAL AND METHODS:
      The study base consisted of a population that was examined on two occasions with
      a 10-year interval, including 91 individuals, 24 smokers, 24 former smokers, and
      43 non-smokers. The assessment of vertical bone loss was based on full sets of
      intra-oral radiographs from both time points. The severity of vertical bone loss
      was expressed as the proportion of proximal sites with vertical defects per
      person. RESULTS: The 10-year increase in the proportion of vertical defects was
      statistically significant in all groups (p<0.001) and, in addition, significantly
      associated with smoking (p<0.05). In particular, the difference between smokers
      and non-smokers was significant (p<0.01) whereas former smokers did not differ
      from non-smokers. Moreover, the 10-year vertical bone loss was significantly
      greater in heavy exposure smokers than in light exposure smokers suggesting an
      exposure-response effect (p<0.01). Compared with non-smokers the unadjusted 10
      year relative risk was 2.3-fold increased in light exposure smokers and 5.3-fold
      increased in heavy exposure smokers (p<0.05). CONCLUSIONS: The present
      observations indicate a significant long-term influence of smoking on vertical
      periodontal bone loss, yielding additional evidence that smoking is a risk factor
      for periodontal bone loss.

PMID- 15966889
TI  - The relationship between selected measures of periodontal status and demographic
      and behavioural risk factors.
AB  - OBJECTIVE: To assess differences between selected periodontal measures by
      demographic and behavioural factors in a nationally representative sample of the
      United States. METHODS: Data for 11,347 person's ages 20-79 years from the third
      National Health and Nutrition Examination Survey (NHANES III) were used. Indices
      and measures constructed from NHANES III data used for this study were: derived
      community periodontal index (dCPI), attachment loss extent index (ALEI),
      attachment loss (AL) scores, and a Periodontal Status Measure (PSM) developed for
      this study. RESULTS: The influence of demographic and behavioural factors varied
      across the four indices examined in multivariate cumulative logistic models.
      Moreover, there was significant effect modification by cigarette smoking with age
      in the ALEI and AL models. The odds ratio (OR) of increasing periodontal disease
      status among 20-39 year olds as measured by AL or ALEI for current smokers
      compared with non-smokers were OR=6.2 (95% confidence interval (CI)=4.1, 8.7) and
      OR=5.6 (95% CI=3.7, 8.7), respectively. In a similar comparison, the OR for dCPI
      was 2.6 (95% CI=1.7, 3.8). Furthermore, Mexican American ethnicity was generally
      not significant in any models using dCPI, PSM, AL, or ALEI and prior dental visit
      was more likely to be significant only in the dCPI and PSM models. DISCUSSION:
      Among the well-known demographic and behavioural influences on periodontal health
      status, some, such as race/ethnicity and prior dental visit status have different
      relationships with differing periodontal measures employed to assess periodontal
      status. Moreover, potential interactions among cofactors also are dependent upon
      the measure selected. Periodontal research findings may be influenced
      significantly by periodontal measure selection and its affect on measurement
      validity. This may have particular relevance to issues concerning disease
      surveillance and assessing reduction of disparities in oral health. Consequently,
      a renewed approach to developing appropriate measures for periodontal
      epidemiology is needed.

PMID- 15966890
TI  - Self-reported oral health, oral hygiene habits, and dental attendance of pregnant
      women in Kuwait.
AB  - OBJECTIVES: The aim of this study was to describe self-reported oral health, oral
      hygiene habits, and frequency of visits to a dentist among pregnant women in
      Kuwait. MATERIAL AND METHODS: A cross-sectional study with an anonymous
      structured questionnaire was distributed among 650 pregnant women during May-June
      2003, when they were admitted to the maternity ward at the largest government
      maternity hospital in Kuwait City. The response rate was 93% (n=603). RESULTS:
      Every fourth respondent was in her first pregnancy, while 36% already had three
      or more children. Every fifth woman felt that her oral health was poor, and one
      third of the women believed that they had periodontal problems currently. About
      two-thirds of the women were brushing more than once a day and almost all (94%)
      at least once a day. Over the previous 6 months, 40% had experienced dental pain.
      Half of the women had visited a dentist during pregnancy, mostly for dental pain.
      Most of the women had received no instructions concerning oral health care during
      their pregnancy. CONCLUSIONS: A large proportion of the pregnant women in this
      study had oral health problems; however, half of the women had not seen a dentist
      during their pregnancy.

PMID- 15966891
TI  - Factors related to utilization of dental services during pregnancy.
AB  - OBJECTIVES: The purposes of this study were to investigate factors related to
      utilization of dental services during pregnancy and to assess the extent of
      mothers' knowledge regarding oral health during pregnancy and its effect on
      pregnancy outcomes. MATERIALS AND METHODS: Cross-sectional data were collected
      from 625 women using a structured questionnaire mailed to mothers who had given
      birth in Johnson County, Iowa from August 2001 to March 2002. The survey assessed
      knowledge, behaviours, attitudes toward dental care during pregnancy, and
      personal, demographic and pregnancy-related factors. Variables which showed
      associations in bivariate analysis (p< or =0.1) were considered as candidates for
      building logistic regression models separately by domain (demographics, dental
      health care behaviours, lifestyle, financial variables, pregnancy-related
      variables, and knowledge of the possible association between oral health and
      pregnancy). Significant domain-specific regression results (p< or =0.05) were
      used to develop a final model using forward stepwise logistic regression
      analyses. RESULTS: The overall response rate was 69%. Dental visits during
      pregnancy were reported by 49% of respondents. Forty-three percent were aware of
      the possible connection between oral health and pregnancy outcomes. In the final
      logistic regression analysis, factors significantly associated with reporting
      dental visits during pregnancy were: (1) personal factors (being married, greater
      frequency of visiting the dentist when not pregnant and use of inter-proximal
      cleaning aids); (2) financial factors (dental insurance); and (3) knowledge of
      the possible connection between oral health and pregnancy outcomes. CONCLUSIONS:
      There was limited knowledge of the possible relationships between oral health and
      pregnancy outcomes in a fairly homogeneous population of women who were of
      relatively high socioeconomic standing. This study suggests that better education
      of the importance of dental care before and during pregnancy is needed.

PMID- 15966892
TI  - Bone height changes in individuals with periodontal disease: a 17-year
      prospective longitudinal study.
AB  - OBJECTIVE: The aim of this study was to analyse changes in bone height after 17
      years in smokers and non-smokers with periodontal disease, and to compare these
      with clinical assessment outcome. MATERIAL AND METHODS: Participants comprised 50
      adults with periodontitis and 18 healthy controls from a randomly selected
      epidemiological sample. Their mean age at the end of the study was 54.2 (SD+/
      3.09) years. The study included radiographic analysis compared with clinical
      data. RESULTS: The periodontitis group had significantly (p<0.001) higher values
      than their healthy counterparts for plaque index (PLI), gingival index (GI),
      calculus index (CI), and bleeding on probing (BOP) at baseline and after 17
      years. At the end of the follow-up, never-smokers with periodontitis had higher
      values for PLI (p<0.05) and ex-smokers and smokers had higher GI and BOP
      (p<0.001) than the controls. In all individuals with periodontitis, maxillary
      molars were most affected. Smokers had more severe marginal bone loss over time.
      Vertical bone defects were more often seen on the mesial side of teeth (p<0.05).
      CONCLUSION: Marginal bone level in this prospective study did reveal tooth groups
      at higher risk for progression of periodontal disease.

PMID- 15966893
TI  - Thickness of gingiva in association with age, gender and dental arch location.
AB  - BACKGROUND: It has been long known that the clinical appearance of healthy
      marginal periodontium differs from subject to subject and even among different
      tooth types. Many features are genetically determined; others seem to be
      influenced by tooth size, shape and position and biological phenomena such as
      gender, growth and age. AIM: The purpose of this study was to determine the
      thickness of facial gingiva among Indians and its association with age, gender
      and dental arch. METHODS: The study group included 16 males and 16 females with
      an age range of 16-38 years. Gingival thickness was assessed in the maxillary and
      mandibular anteriors by transgingival probing. RESULTS: It was observed that the
      younger age group had significantly thicker gingiva than that of the older age
      group. The gingiva was found to be thinner in females than males and, in the
      mandibular arch than the maxilla. CONCLUSION: In the present study, it was
      concluded that gingival thickness varies according to age, gender and dental
      arch.

PMID- 15966894
TI  - Management of inter-dental/inter-implant papilla.
AB  - OBJECTIVES: The aims of this paper are to review and compare existing techniques
      for creation of interdental/interimplant papillae, to address factors that may
      influence its appearance and to present an approach that authors developed that
      could help clinicians to manage and recreate the interproximal papillae. METHODS:
      Papers related to interdental and interimplant papillae published over the last
      30 years were selected and analyzed. RESULTS: Thorough treatment planning is
      essential for maintenance of the height of the interproximal papillae following
      tooth removal. The key for achieving an esthetically pleasing outcome is the
      clinicians' ability of properly managing/creating interdental/interimplant
      papillae. Bone support is the foundation for any soft tissue existence,
      techniques such as socket augmentation, orthodontic extrusion, guided bone
      regeneration, onlay graft and distraction osteogenesis are often used for this
      purpose. Soft tissue grafts as well as esthetic mimic restorations can also be
      used to enhance the esthetic outcomes. CONCLUSIONS: An esthetic triangle is
      developed to address the foundations that are essential for maintaining/creating
      papilla. These include adequate bone volume, proper soft tissue thickness as well
      as esthetic appearing restorations.

PMID- 15966895
TI  - Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding
      protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1.
AB  - Aurora-A is a centrosomal serine-threonine kinase that regulates mitosis. Over
      expression of Aurora-A has been found in a wide range of tumors and has been
      implicated in oncogenic transformation. However, how Aurora-A over-expression
      contributes to promotion of carcinogenesis remains elusive. Immunohistochemical
      analysis of breast tumors revealed that over-expressed Aurora-A is not restricted
      to the centrosomes but is also found in the cytoplasm. This over-expressed Aurora
      A appeared to be phosphorylated on Thr288, which is known to be required for its
      enzymatic activation. In analogy to Aurora-A's role in oocyte maturation and the
      early embryonic cell cycle, here we investigated whether ectopically over
      expressed Aurora-A can similarly stimulate polyadenylation of mRNA in human
      somatic cultured cells by interacting with a human ortholog of cytoplasmic
      polyadenylation element binding protein, h-CPEB. In vitro experiments revealed
      that Aurora-A binds directly to, and phosphorylates, h-CPEB. We found that
      polyadenylation of mRNA tails of cyclin B1 and Cdk1 was synergistically
      stimulated when Aurora-A and h-CPEB were over-expressed, and they were further
      promoted in the presence of an Aurora-A activator Ajuba. Our results suggest a
      function of ectopically over-expressed Aurora-A that might be relevant for
      carcinogenesis.

PMID- 15966896
TI  - Molecular mechanism of ubiquitin recognition by GGA3 GAT domain.
AB  - GGA (Golgi-localizing, gamma-adaptin ear domain homology, ARF-binding) proteins,
      which constitute a family of clathrin coat adaptor proteins, have recently been
      shown to be involved in the ubiquitin-dependent sorting of receptors, through the
      interaction between the C-terminal three-helix-bundle of the GAT (GGA and Tom1)
      domain (C-GAT) and ubiquitin. We report here the crystal structure of human GGA3
      C-GAT in complex with ubiquitin. A hydrophobic patch on C-GAT helices alpha1 and
      alpha2 forms a binding site for the hydrophobic Ile44 surface of ubiquitin. Two
      distinct orientations of ubiquitin Arg42 determine the shape and the charge
      distribution of ubiquitin Ile44 surface, leading to two different binding modes.
      Biochemical and NMR data strongly suggest another hydrophobic binding site on C
      GAT helices alpha2 and alpha3, opposite to the first binding site, also binds
      ubiquitin although weakly. The double-sided ubiquitin binding provides the GAT
      domain with higher efficiency in recognizing ubiquitinated receptors for
      lysosomal receptor degradation.

PMID- 15966897
TI  - Activation of c-Jun amino-terminal kinase by GDNF induces G2/M cell cycle delay
      linked with actin reorganization.
AB  - It is well known that the cell cycle is controlled by several cyclin/cyclin
      dependent kinase (Cdk) complexes whose expression and phosphorylation states vary
      with orderly periodicity. During the cell cycle, activity of the cyclin/Cdk
      complexes can be regulated directly or indirectly by a number of molecules,
      including protein kinases and phosphatases, p53, and Cdk inhibitors. Here, we
      show that the addition of glial cell line-derived neurotrophic factor (GDNF)
      induced G2/M cell cycle delay in human SK-N-MC neuroectodermal tumor cells that
      express RET tyrosine kinase, accompanying actin reorganization. Cell cycle delay
      at G2/M was characterized by accelerated and prolonged Cdc2 phosphorylation and
      stabilization of cyclin B1 and Wee1 kinase expression. Interestingly, we found
      that phosphorylation and/or expression of Cdc2, cyclinB1, and Wee1 was controlled
      by the Rac1/c-Jun NH2-terminal kinase (JNK) pathway. Immunohistochemical analysis
      suggested that the G2/M cell cycle delay may be necessary to prevent the mitotic
      progression of SK-N-MC cells with perturbed actin cytoskeletons.

PMID- 15966898
TI  - Fhos2, a novel formin-related actin-organizing protein, probably associates with
      the nestin intermediate filament.
AB  - Fhos1 is a mammalian formin-family protein, and functions as an organizer of the
      actin microfilament. Here we have cloned human and mouse cDNAs for a novel Fhos
      homolog, designated Fhos2. The messages for Fhos2 are expressed in the heart,
      kidney, and brain, where the Fhos1 mRNAs are not abundant. Two splice variants of
      Fhos2 exist in a tissue-specific manner; the longer variant Fhos2L is the major
      form in the heart, whereas the kidney and brain predominantly express Fhos2S that
      encodes a shorter protein. Over-expression of an active form of the two Fhos2
      variants, as well as that of Fhos1, induces the formation of actin stress fibers
      in HeLa cells, suggesting that Fhos2 acts as an actin-organizing protein.
      Biochemical analysis using rat cardiomyoblastic H9c2 (2-1) cells reveals that
      endogenous Fhos2 is enriched in the intermediate filament fraction. Consistent
      with this, Fhos2 localizes to the nestin intermediate filament but not to other
      cytoskeletons, as demonstrated by staining of H9c2 (2-1) cells with anti-Fhos2
      antibodies. Furthermore, Fhos2 is present in nestin-expressing neuroepithelial
      cells of the fetal rat brain. Thus, Fhos2 not only has the actin-organizing
      activity but also associates with nestin, which may imply a Fhos2-mediated link
      between the nestin intermediate filament and actin microfilament.

PMID- 15966899
TI  - Multiple roles of Rbx1 in the VBC-Cul2 ubiquitin ligase complex.
AB  - The importance of the ubiquitin system largely depends on ubiquitin ligases, E3s,
      as they determine the specificity of the system. Rbx1/ROC1/Hrt1, a RING finger
      protein, functions as an important component of the cullin-containing SCF and VBC
      Cul2 ligases. Modification of cullins by NEDD8 (NEDDylation), has been shown to
      be essential for the E3 activity of both SCF and VBC-Cul2, and it was suggested
      that Rbx1 acts as the E3 for cullin NEDDylation. RING finger is composed of eight
      cysteine and histidine residues that bind to zinc ions. Rbx1 is a highly
      evolutionarily conserved protein; however, the eighth coordination residue in its
      RING finger is aspartate (D97) rather than cysteine. Substitution of D97 with
      each of the other 19 amino acids demonstrates that aspartate is superior to
      cysteine in cullin NEDDylation. Interestingly, however, different D97 mutants
      demonstrate different activities towards 6 cullins tested. Importantly, we were
      able to discriminate between the NEDDylating activity of Rbx1 and its involvement
      in the ubiquitylation reaction within the context of VBC-Cul2. Moreover, while
      Rbx1 is not involved in governing the stability of SCF, Rbx1 mutants destabilize
      VBC-Cul2. Taken together, these results indicate that various mechanisms regulate
      both the activities and the stability of cullin-based ligases.

PMID- 15966900
TI  - Rapid turnover of GATA-2 via ubiquitin-proteasome protein degradation pathway.
AB  - Transcription factor GATA-2 is expressed in a number of tissues, including
      hematopoietic stem and progenitor cells, and is crucial for the proliferation and
      survival of hematopoietic cells. To further characterize the function of GATA-2,
      we examined the cellular turnover mechanism of GATA-2. In P815 cells, the half
      life of endogenous GATA-2 was found to be as short as 30 min after cycloheximide
      treatment. This short half-life was reproducible in other hematopoietic and
      neuroblastoma cell lines with moderate variation. We also found that ultraviolet
      (UV)-C irradiation markedly represses the GATA-2 protein level by facilitating
      the degradation process. Since treatment of the cells with the proteasome
      inhibitor MG132 or clasto-Lactacystin substantially abrogated the effects of
      cycloheximide and UV-C irradiation and increased the expression level of both
      endogenous and transfected GATA-2, the degradation of GATA-2 seems to occur
      through the proteasome pathway. Structure-function analyses with the GAL4-DNA
      binding domain (GBD)-GATA-2 fusion protein and GATA-2 deletion mutants suggested
      that the protein degradation regulatory elements of GATA-2 reside in three
      regions, two of which overlap with the transactivation domain. We also detected
      poly ubiquitinated forms of GATA-2. Taken together, these results demonstrate
      that GATA-2 is turned over rapidly through the ubiquitin-proteasome pathway.

PMID- 15966901
TI  - DNA polymerase lambda directly binds to proliferating cell nuclear antigen
      through its confined C-terminal region.
AB  - DNA polymerase lambda (Pol lambda) was recently identified as a new member of the
      family X of DNA polymerases. Here, we show that Pol lambda directly binds to
      proliferating cell nuclear antigen (PCNA), an auxiliary protein for DNA
      replication and repair enzymes, both in vitro and in vivo. A pull-down assay
      using deletion mutants of Pol lambda showed that the confined C-terminal region
      of Pol lambda directly binds to PCNA. Furthermore, a synthetic peptide of 20-mers
      derived from the C-terminal region of Pol lambda competes with full-length Pol
      lambda for binding to PCNA. The residues between amino acids 518 and 537 of Pol
      lambda are required for binding to PCNA, and are different from the consensus
      PCNA interacting motif (PIM). Pol lambda associates with PCNA in vivo by
      immunoprecipitation analysis and EGFP-tagged Pol lambda co-localizes with PCNA as
      spots within a nucleus using fluorescent microscopy. Through direct binding, PCNA
      suppressed the distributive nucleotidyltransferase activity of Pol lambda. Pol
      micro, which also belongs to the family X of DNA polymerases, binds to PCNA by a
      pivotal amino acid residue.

PMID- 15966902
TI  - GABP, HCF-1 and YY1 are involved in Rb gene expression during myogenesis.
AB  - Muscle cell differentiation, or myogenesis, is a well-characterized process and
      involves the expression of specific sets of genes in an orderly manner. A
      prerequisite for myogenesis is the exit from the cell cycle, which is associated
      with the up-regulation of the tumor suppressor Rb. In this study, we set to
      investigate the regulatory mechanism of the Rb promoter that allows adequate up
      regulation in differentiating myoblasts. We report that Rb expression is
      regulated by the transcription factors GABP, HCF-1 and YY1. Before induction of
      differentiation, Rb is expressed at a low level and GABP and YY1 are both present
      on the promoter. YY1, which exerts an inhibitory effect on Rb expression, is
      removed from the promoter as cells advance through myogenesis and translocates
      from the nucleus to the cytoplasm. On the other hand, upon induction of
      differentiation, the GABP cofactor HCF-1 is recruited to and coactivates the
      promoter with GABP. RNAi-mediated knock-down of HCF-1 results in inhibition of Rb
      up-regulation as well as myotube formation. These results indicate that the Rb
      promoter is subject to regulation by positive and negative factors and that this
      intricate activation mechanism is critical to allow the accurate Rb gene up
      regulation observed during myogenesis.

PMID- 15966903
TI  - A decreased level of FtsZ is responsible for inviability of RNase E-deficient
      cells.
AB  - The endoribonuclease RNase E, encoded by the essential gene rne, plays a major
      role in cellular RNA metabolism, i.e. maturation of functional RNAs such as rRNA
      and tRNA, degradation of many mRNAs and processing of the ftsZ mRNA which encodes
      the essential cell division protein FtsZ. RNase E function is somehow regulated
      by the RNA binding protein Hfq. We found that temperature-sensitive colony
      formation of a rne-1 mutant was partially suppressed by introduction of a
      hfq::cat mutation. Neither accumulation of rRNA and tRNA(Phe) precursors nor
      incomplete processing of ftsZ mRNA in the rne-1 mutant was rescued by the
      hfq::cat mutation. However, the amount of FtsZ protein that was decreased in the
      rne-1 mutant was recovered up to a level similar to that of wild-type cells by
      the hfq::cat mutation. Overproduction of Hfq inhibited cell division because of
      decreased expression of FtsZ. Artificial expression of the FtsZ protein from a
      plasmid-borne ftsZ gene partially suppressed the temperature-sensitivity of the
      rne-1 mutant. These results suggest that the decreased level of FtsZ is, at least
      in part, responsible for the inviability of RNase E-deficient cells.

PMID- 15966904
TI  - Cell-type specific utilization of multiple negative feedback loops generates
      developmental constancy.
AB  - Signaling pathways generally contain multiple negative regulators that are
      induced by the signal they repress, constructing negative feedback loops.
      Although such negative regulators are often expressed in a tissue- or cell-type
      specific manner during development, little is known about the significance of
      their differential expression patterns and possible interactions. We show the
      role and interplay of two cell-type specific negative feedback loops during
      specification of photoreceptor neurons in the Drosophila compound eye, a process
      that occurs via epidermal growth factor (EGF)-mediated sequential induction
      through the activation of the Ras/MAPK signaling pathway. Inducing cells
      secreting EGF express a negative regulator Sprouty (SPRY) that lowers Ras/MAPK
      signaling activity, and as a consequence reduces the signal-dependent expression
      of a secreted EGF inhibitor, Argos (AOS). Induced cells in turn express an orphan
      nuclear receptor Seven-up (SVP), which represses SPRY expression thereby allowing
      expression and secretion of AOS, preventing further induction. When this
      intricate system fails, as in spry mutants, sequential induction is no longer
      constant and the number of photoreceptor neurons becomes variable. Thus, cell
      type specific utilization of multiple negative feedback loops not only confers
      developmental robustness through functional redundancy, but is a key component in
      generating consistent patterning.

PMID- 15966905
TI  - Inflammatory bone destruction and osteoimmunology.
AB  - OBJECTIVES: The metabolism of hard tissue is influenced by the immune system.
      Research into the bone destruction associated with inflammatory diseases such as
      periodontal disease and rheumatoid arthritis has highlighted the importance of
      the interplay of the immune and skeletal systems. This interdisciplinary research
      field, called 'osteoimmunology', has become increasingly important for each
      system by itself as well as the biology linking them. The history and recent
      progress of this field are reviewed. MATERIAL AND METHODS: 'Osteoimmunology' was
      coined to describe the pioneering work on the T-cell regulation of
      osteoclastogenesis by the receptor activator of nuclear factor-kappaB ligand
      (RANKL) and interferon (IFN)-gamma. Accumulating evidence suggests that the
      immune and skeletal systems share not only cytokines but also various signaling
      molecules, transcription factors and membrane receptors. The contribution of T
      cells to the pathogenesis of inflammatory bone destruction is discussed, and our
      recent findings are summarized to illustrate how the osteoimmunological network
      functions. RESULTS: RANKL is an osteoclastogenic cytokine that links bone and the
      immune system. Immunomodulatory cytokines such as IFNs also participate in the
      regulation of RANKL signaling and inflammatory bone loss. The transcription
      factor nuclear factor of activated T cells c1 (NFATc1) has been identified as a
      master switch regulator of osteoclastogenesis. In addition, immunoglobulin-like
      receptors are critically involved in bone homeostasis. CONCLUSION: Bone turns out
      to be a dynamic tissue that is constantly renewed, where the immune system
      participates to a hitherto unexpected extent. This emerging field will be of
      great importance to a better understanding and treatment of diseases of the
      skeletal and immune systems, as well as to the fundamental biology underpinning
      both.

PMID- 15966906
TI  - Real-time polymerase chain reaction quantification of Epstein--Barr virus in
      chronic periodontitis patients.
AB  - BACKGROUND: Although herpes viruses have been implicated in the pathogenesis of
      chronic and aggressive periodontitis, few data in the literature refer to
      quantification of these viruses in periodontal sites, especially in relation to
      serological findings. OBJECTIVE: The aim of the present study was to compare
      Epstein--Barr virus (EBV) DNA load in subgingival specimens from chronic
      periodontitis patients and in periodontally healthy subjects, in relation to
      serologic testing of IgM and IgG antibodies to EBV. METHODS: A total of 22
      chronic periodontitis patients and 13 controls participated in the present study.
      Seventy-nine subgingival specimens (one pooled, one from a deep and one from a
      shallow site), sampled with paper points, were analysed with real-time polymerase
      chain reaction for EBV. Subjects were also examined for anti-EBV IgG and IgM
      levels in serum, using an enzyme-linked immunosorbent assay. RESULTS: One subject
      was seronegative for EBV. Three subjects (one patient and two controls) displayed
      anti-EBV IgM. Their data were excluded from further analysis. All three displayed
      EBV in their subgingival samples. Nine out of the remaining 20 chronic
      periodontitis patients and 10 out of 11 controls did not display EBV
      subgingivally. A statistically significant difference in viral load was observed
      between pooled and shallow-pocket samples from periodontitis patients but not
      between samples from deep and shallow pockets (Kruskall--Wallis anova, Dunn's
      multiple comparisons test). CONCLUSIONS: Data from the present study do not
      strongly support the pathogenetic significance of EBV in chronic periodontitis
      lesions. The data do, however, suggest that parallel serological assessments
      provide a useful insight into the association of viruses with periodontal
      disease.

PMID- 15966907
TI  - Formation and resolution of ankylosis under application of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) to class III furcation defects in cats.
AB  - OBJECTIVES: Periodontal regeneration under application of bone morphogenetic
      protein (BMP) is compromised by ankylosis. Ankylosis disappearance following
      application of BMP has been observed in the case of a small defect, which might
      be beneficial change for periodontal regeneration. However, the histological
      observation of ankylosis disappearance has not been demonstrated in a large
      defect. The purpose of this present study was to confirm resolution of ankylosis
      during periodontal regeneration by recombinant human BMP-2 (rhBMP-2) applied to
      class III furcation defects. MATERIAL AND METHODS: Class III furcation defects
      were created in the premolars of six adult cats. The rhBMP-2 material, prepared
      by applying rhBMP-2 to a combination of polylactic acid-polygricolic copolymer
      and gelatin sponge (PGS; 0.33 microg rhBMP-2/mm(3) PGS) or control material
      containing only PGS, was implanted into each defect. The cats were killed at 3, 6
      or 12 weeks after surgery and serial sections were prepared for histological and
      histometrical observation. RESULTS: Ankylosis was observed in some of the rhBMP
      2/PGS group at 3 and 6 weeks, but not at 12 weeks. At 6 weeks, osteoclast-like
      cells were visible in the rhBMP-2/PGS group with ankylosis. Residual PGS was
      evident between the bone and root surface in the rhBMP-2/PGS group without
      ankylosis at 3 weeks. CONCLUSIONS: Resolution of ankylosis by osteoclast-like
      cells possibly occurred under application of rhBMP-2. Residual PGS might play an
      important role in preventing ankylosis formation.

PMID- 15966908
TI  - A functional interleukin-1 beta gene polymorphism is associated with chronic
      periodontitis in a sample of Brazilian individuals.
AB  - BACKGROUND: Interleukin-1 beta (IL-1 beta) is a potent inflammatory mediator and
      an important polymorphism in the locus +3954 (C/T) of the human IL1 B gene has
      been shown to affect the levels of this cytokine. This functional polymorphism
      has been associated with the establishment of inflammatory diseases, including
      periodontal disease, in European, Asian and North American populations.
      OBJECTIVE: The aim of this study was to investigate the association between the
      IL1 B (+3954) gene polymorphism and the occurrence of different clinical forms of
      periodontitis in a sample of Brazilian individuals. METHODS: This study employed
      a cross-sectional design involving individuals from the State of Minas Gerais in
      the south-eastern region of Brazil. Genomic DNA was obtained from oral swabs of
      129 individuals and amplified using the polymerase chain reaction (PCR) with
      specific primers flanking the locus +3954 of IL1 B. PCR products were submitted
      to restriction endonuclease digestion and analyzed by polyacrylamide gel
      electrophoresis, to distinguish alleles T and C of the IL1 B gene, allowing for
      the determination of the genotypes and detection of the polymorphism. RESULTS AND
      CONCLUSIONS: The chronic periodontitis group displayed a higher percentage of the
      T allele (28%) when compared to the aggressive periodontitis group (10.7%,
      chi(2)=5.24, p=0.02, OR=0.31, CI=0.11--0.88) and to control group (8.7%,
      chi(2)=7.11, p=0.007, OR=0.24, CI=0.08--0.73). Our data suggested that the
      polymorphism in the locus +3954 of IL1 B gene could be a risk factor for chronic
      periodontitis in a sample of Brazilian individuals.

PMID- 15966909
TI  - Distinctive localization and function for lumican, fibromodulin and decorin to
      regulate collagen fibril organization in periodontal tissues.
AB  - BACKGROUND: Small leucine-rich proteoglycans (SLRPs) decorin, biglycan,
      fibromodulin and lumican are secreted extracellular matrix molecules that
      associate with fibrillar collagens and regulate collagen fibrillogenesis.
      Collagens are the major extracellular matrix components of periodontal connective
      tissues where they provide mechanical attachment of the tooth to the bone and
      gingiva and mediate signals that regulate cell functions, including remodeling of
      the periodontal ligament and bone. Structural organization of collagen may also
      be important for the defense against periodontal disease, because in certain
      conditions abnormal collagen fibrils associate with increased susceptibility to
      periodontal disease. OBJECTIVES: The purpose of this study was to find out the
      role of SLRPs to regulate collagen fibril and fibril bundle formation in
      periodontal tissues. METHODS: The localization of SLRPs in human and mouse
      periodontal tissues was studied using immunohistochemical methods. To assess the
      function of SLRPs we studied periodontal tissues of mice harboring targeted
      deletions of decorin, fibromodulin or lumican genes and lumican and fibromodulin
      double knockout mice using histological and electronmicroscopical methods.
      RESULTS: The SLRPs were coexpressed in human and mouse gingival and periodontal
      ligament connective tissues where they colocalized with collagen fibril bundles.
      Teeth in the knockout animals were fully erupted and showed normal gross
      morphology. Targeted deletion of decorin, fibromodulin, lumican or both lumican
      and fibromodulin resulted in abnormal collagen fibril and fibril bundle
      morphology that was most evident in the periodontal ligament. Each of the gene
      deletions resulted in a unique fibril and fibril bundle phenotype. CONCLUSIONS:
      These findings indicate that decorin, fibromodulin and lumican coordinately
      regulate the fibrillar and suprafibrillar organization of collagen in the
      periodontal ligament.

PMID- 15966910
TI  - Chemical sympathectomy inhibits periodontal disease in Fischer 344 rats.
AB  - OBJECTIVE: The responsiveness of the sympathetic nervous system (SNS) and the
      hypothalamic--pituitary--adrenal (HPA) axis plays a major role in immune
      regulation and for the outcome of infections and inflammatory disorders. This
      study was designed to investigate whether chemical SNS denervation with the
      noradrenaline-selective neurotoxic drug 6-hydroxydopamine (6-OHDA), which
      destroys peripheral noradrenaline terminals, would influence immune responses to
      Gram-negative bacterial lipopolysaccharide (LPS) stimulation, and the progression
      of ligature-induced periodontal disease in Fischer 344 rats. MATERIAL AND
      METHODS: 6-OHDA (40--60 microg/kg) or vehicle was injected intraperitoneally
      (i.p.) on days 1, 3 and 5, 10 days before application of the ligatures, and
      thereafter weekly in doses of 80 microg/kg. Periodontal disease was assessed when
      the ligatures had been in place for 49 days. At 24 and 2 h before decapitation,
      all rats received LPS (150 microg/kg i.p.) to induce a robust immune and HPA axis
      response. RESULTS: The 6-OHDA-treated rats showed significantly reduced bone loss
      as measured by digital X-rays (p< 0.01), and enhanced levels of the cytokines
      transforming growth factor-beta (p=0.05) and interleukin-6 (p=0.05), as well as
      the HPA axis derived hormone corticosterone (p=0.01), induced by LPS stimulation.
      CONCLUSIONS: 6-OHDA-induced chemical sympathectomy inhibits ligature-induced
      periodontal disease in this model. This effect may be attributable to the well
      documented ability of the SNS to regulate immune system function primarily via
      the adrenergic neurotransmitter noradrenaline released at sympathetic nerve
      terminals. The enhanced HPA axis activation may be a compensatory response that
      reduces the T helper (Th)2 to Th1 skewing effect of treatment with 6-OHDA.

PMID- 15966911
TI  - Relationship between periodontal disease status and combination of biochemical
      assays of gingival crevicular fluid.
AB  - BACKGROUND: Currently, no biochemical assay involving gingival crevicular fluid
      is utilized routinely as a screening test for periodontal disease. OBJECTIVE: The
      objective of the present study was to evaluate the potential of gingival
      crevicular fluid assay as a screening methodology. METHODS: The subject
      population was comprised of 27 volunteers. Nine participants were classified as
      'subject with periodontal destruction' (SPD) exhibiting at least one site with
      pocket depth and attachment loss>3.5 mm, whereas the remaining individuals were
      categorized as 'subject with minimal periodontal destruction' (SMD). Gingival
      crevicular fluid was collected from fixed sites via a standardized method.
      Biochemical assays of 12 substances (hemoglobin, albumin, transferrin, alpha(1)
      antitrypsin, fibronectin, IgA, IgG, IgM, lactoferrin, myeloperoxidase and
      neutrophil elastase) were conducted at a commercial laboratory. Power
      transformation of total quantities in gingival crevicular fluid was performed for
      statistical analysis. RESULTS: Relationships between total quantity of each
      substance and periodontal disease status were unclear. Logistic regression
      analysis yielded six predictive models, which consisted of substance pairs:
      neutrophil elastase/IgA, neutrophil elastase/hemoglobin, neutrophil
      elastase/alpha(1)-antitrypsin and neutrophil elastase/IgG, and IgA/albumin and
      IgA/transferrin (p<0.05). Regression lines for SPD and SMD on a scattergram of
      IgA and neutrophil elastase were nearly parallel within the range of amounts in
      gingival crevicular fluid. The predictive model derived from both substances
      afforded sensitivity and specificity of 88% and 94%, respectively. CONCLUSIONS:
      These results indicated that the combination of IgA and neutrophil elastase in
      gingival crevicular fluid may be crucial for prediction of periodontal disease
      status. Furthermore, these data suggested that biochemical assays employing both
      substances in gingival crevicular fluid may provide a satisfactory screening test
      for periodontal disease.

PMID- 15966912
TI  - Periodontal status and preterm low birth weight: a case control study.
AB  - BACKGROUND: Previous studies have suggested that periodontal disease may be an
      important risk factor for preterm low birth weight. However, the link between
      periodontal health status of pregnant women and preterm low birth weight is
      contentious, as recent studies found no association between periodontitis and
      pregnancy outcome. OBJECTIVE: The aim of this study was to investigate this
      potential link in a German Caucasian population. METHODS: Fifty-nine pregnant
      women with a high risk for a preterm low birth weight infant (suffering from
      preterm contractions, cases, group 1) as well as 42 control women with no preterm
      contractions during pregnancy and having an infant appropriate for date and
      weight (>or= 37 weeks gestation, >or= 2500 g, group 2) were examined. Clinical
      periodontal status was recorded on a full mouth basis. Subgingival plaque samples
      were taken and periodontal pathogens were identified by polymerase chain
      reaction. Additionally, interleukin-1 beta level in gingival crevicular fluid was
      analysed. RESULTS: The mean percentage of sites showing moderate to advanced
      attachment loss (>or=3 mm) was low in all study groups (group 1: 9.9 +/- 11.2%;
      group 2:10.6 +/- 14.1%, respectively). No significant differences between the
      groups in any aspects of the studied periodontitis parameters could be detected.
      Using a logistic regression model controlling for known preterm low birth weight
      risk factors, no periodontitis-associated factors increased risk for preterm
      contractions or preterm low birth weight. The odds ratio (OR) was 1.19 for
      preterm contractions, the 95% confidence interval (CI) 0.46; 3.11 and 0.73 for
      preterm low birth weight; 95% CI: 0.13; 4.19, respectively. CONCLUSION: In this
      population, periodontitis was not a detectable risk factor for preterm low birth
      weight in pregnant women.

PMID- 15966913
TI  - Relationship between obesity, glucose tolerance, and periodontal disease in
      Japanese women: the Hisayama study.
AB  - BACKGROUND: Recent studies have reported a relationship between obesity and
      periodontal disease. Obesity is the strongest risk factor for type 2 diabetes,
      which is, in turn, a risk factor for periodontal disease. An oral glucose
      tolerance test is necessary to diagnose diabetes; however, no study has examined
      the relationship between obesity and periodontal disease by taking oral glucose
      tolerance test results into consideration. METHODS: In all, 584 Japanese women
      aged between 40 and 79 years old, with at least 10 teeth, underwent health
      examinations. Body mass index, waist-hip ratio, body fat, and oral glucose
      tolerance test results were used as independent variables with known risk factors
      for periodontal disease. Mean probing pocket depth and mean attachment loss were
      used as the dependent variables. RESULTS: In all of the analyses, body mass
      index, body fat, and waist--hip ratio were significantly associated with the
      highest quintile of mean probing pocket depth, even when adjusted for oral
      glucose tolerance test results. In the multivariate analysis, the subjects with
      the highest quartile of body mass index had a significantly higher odds ratio
      (OR) for the highest quintile of mean probing pocket depth [OR, 4.3; 95%
      confidence interval (CI), 2.1--8.9; p<0.001], whereas neither impaired glucose
      tolerance nor diabetes were significantly associated with deep pockets. The
      relationships between the obesity indexes and mean attachment loss did not reach
      statistical significance. CONCLUSION: Obesity was associated with deep pockets in
      Japanese women, even after adjusting for oral glucose tolerance test.

PMID- 15966914
TI  - Cytoskeleton and surface structures of cells directly attached to the tooth in
      the rat junctional epithelium.
AB  - OBJECTIVE: It is still an open question whether cells directly attached to the
      tooth (DAT) cells are migratory or non-migratory cells. The purpose of this study
      was to examine cytoskeletal and surface structures of DAT cells that might be
      involved in migration. METHODS: We investigated the distribution of stress fibers
      composed of actin filaments in DAT cells using phallacidin fluorescent dye
      methods in a confocal laser scanning microscope. To observe the three-dimensional
      structure of the DAT cell surface, the osmium maceration scanning electron
      microscope (SEM) method, which removes various soluble materials between DAT
      cells and the enamel, was employed. RESULTS: Stress fibers were found in the most
      apically located DAT cells, and were arranged in parallel to the presumable
      cervical-line, whereas some of the fibers ran parallel to the tooth axis in the
      more coronally located DAT cells. The parallel arrangement to the tooth axis of
      the fibers may be involved with migration for turnover, and the parallel
      accumulation to the presumable cervical-line may be concerned with the cervical
      contraction of DAT cells. Osmium maceration SEM images at high magnification
      revealed the existence of microvilli-like structures on the enamel surfaces
      (facing to the tooth surface) of DAT cells after removal of the soluble matrices.
      The thicknesses of the microvilli-like structures on the enamel surfaces and cell
      processes of intercellular bridges were significantly different. CONCLUSION: DAT
      cells possess stress fibers arranged in parallel to the tooth axis and to the
      presumable cervical-line in the cytoplasm, and microvilli-like structures on
      their enamel surfaces. These results suggest that these structures contribute to
      DAT cell migration.

PMID- 15966915
TI  - The torch passes.

PMID- 15966917
TI  - Ischemia-driven target vessel revascularization after-primary percutaneous
      coronary intervention: patients at risk and their outcomes.
AB  - Clinical and angiographic correlates of ischemia-driven target vessel
      revascularization (ITVR) in patients undergoing primary percutaneous coronary
      interventions (PCI) are currently less well known. Accordingly, we examined 2,981
      patients enrolled in different Primary Angioplasty in Myocardial Infarction
      trials, who underwent primary PCI to evaluate risk factors and outcomes of
      individuals requiring subsequent ITVR. At 6 months, ITVR was required in 321
      patients (11%). Compared to the cohort without ITVR, patients requiring ITVR were
      younger (P=0.036), females (P=0.018), and more likely to have systolic blood
      pressure >100 mmHg on presentation (P=0.022), family history of premature
      coronary artery disease (P=0.035), and postprocedure dissection (P=0.001). In
      contrast, Killip Class >I on presentation (P=0.05), left circumflex as infarct
      related artery (P=0.022), and the use of ticlopidine (P=0.044) and stents
      (p=0.057) were less frequent among ITVR patients. Multivariate analysis
      identified younger age (for each 10-year decrease, odds ratio [OR], 1.18; 95%
      confidence interval [CI], 1.06-1.32), female gender (OR: 1.41, 95% CI: 1.05
      1.89), and final dissection (OR: 1.69, 95% CI: 1.23-2.33) as independent risk
      factors for ITVR. In-hospital reinfarction (P < 0.001) was increased and at 6
      months remained higher in ITVR patients; in-hospital and 6-month mortality did
      not differ between the two groups. Our study identifies the incidence, risk
      factors, and outcomes of patients requiring ITVR after primary PCI. Importantly,
      our data suggest that no increase in mortality occur, if ITVR is promptly
      performed to treat recurrent ischemia after primary PCI.

PMID- 15966918
TI  - Alcohol septal ablation for hypertrophic obstructive cardiomyopathy.
AB  - HOCM is a rare disorder of myocardium that may result in asymmetrical left
      ventricular septal hypertrophy and dynamic outflow obstruction. This may result
      in hemodynamic sequel that leads to deterioration of functional class in the
      majority of patients. Alcohol septal ablation may provide symptomatic relief in
      the majority of patients who fail medical therapy or who experience significantly
      high outflow gradients.

PMID- 15966919
TI  - Evaluation of safety of warfarin in combination with antiplatelet therapy for
      patients treated with coronary stents for acute myocardial infarction.
AB  - The safety and efficacy of treating recently stented patients on combination
      antiplatelet therapy with warfarin for clinical indications in unknown.
      Therefore, we examined the use of warfarin in a population of patients with
      myocardial infarction (MI) treated with coronary stenting. We performed a
      retrospective analysis comparing patients who underwent successful coronary
      stenting for acute MI and were discharged on either warfarin and combination
      platelet therapy for clinical indications or combination antiplatelet therapy
      alone. There was a nonsignificant trend toward reinfarction at 6 and 12 months in
      warfarin-treated patients. Warfarin-treated patients had significantly higher
      rates of transfusion compared to nonwarfarin-treated patients at 12 months (21%
      vs 0%, P=0.028). There were no significant predictors of reinfarction in 6 and 12
      months in multivariate analysis. These data demonstrate that warfarin
      anticoagulation, in combination with successful coronary stenting for acute MI
      and antiplatelet therapy, does not reduce risk of reinfarction but is associated
      with increased rates of transfusion.

PMID- 15966920
TI  - Thrombolysis increases the risk of free wall rupture in patients with acute
      myocardial infarction undergoing percutaneous coronary intervention.
AB  - In spite of the progress made in acute angiographic evaluation and obtaining
      durable reperfusion of acute myocardial infarction (AMI) in the past two decades,
      cardiac free wall rupture (FWR) is still one of the causes of mortality following
      AMI. In this study, we evaluated the role of thrombolysis in the risk of FWR in
      AMI patients treated with acute percutaneous coronary intervention (PCI). Among
      3,786 consecutive AMI patients seen between 1985 and 2003, 3,066 patients were
      treated by primary PCI or rescue PCI, with or without additional thrombolysis.
      FWR occurred in 24 of 3,066 patients (0.8%) treated by PCI; female gender (1.4%
      vs 0.6%, P=0.001), age >75 years, (1.4% vs 0.6%, P=0.001) left main coronary
      artery (LMCA)-related infarction, (4.5% vs all other arteries, P=0.015), and
      thrombolytic use (3.1% vs 0.4%, P<0.001) were all associated with higher rates of
      FWR by univariate analysis. In patients treated with PCI and thrombolysis, FWR
      occurred in 2.7% with optimal PCI results but in only 4.9% if PCI was
      unsuccessful (P=NS). The incidence of FWR in patients with optimal PCI without
      thrombolysis was 0.4% (P<0.001). Multivariable analysis identified thrombolytic
      use (odds ratio [OR]: 8.49, 95% confidence interval [CI]: 3.66-19.7, P<0.001),
      LMCA-related infarction (OR: 7.06, 95% CI: 1.89-26.4, P=0.004), and female gender
      (OR: 3.02, 95% CI: 1.27-7.21, P=0.013) as independent predictors of FWR.
      Thrombolysis is one of the contributing causes of FWR in AMI patients undergoing
      PCI, even when PCI is successful.

PMID- 15966921
TI  - Interventional closure with Amplatzer PFO occluder of patent foramen ovale in
      patients with paradoxical cerebral embolism.
AB  - Percutaneous transcatheter closure has been proposed as an alternative to
      surgical closure or long-term anticoagulation in patients with presumed
      paradoxical embolism and patent foramen ovale (PFO). We report our mid-term
      results of 55 consecutive symptomatic patients (mean age: 47 years, range: 20-79)
      who underwent percutaneous transcatheter closure of PFO after at least one event
      of cerebral ischemia; 16 (29%) patients had at least one transient ischemic
      attack and 39 (71%) patients at least one embolic stroke. Multiple embolic events
      had occurred in 6 (11%) patients. Percutaneous transcatheter closure was
      technically successful in all 55 patients (100%). For the majority of patients,
      an Amplatzer PFO occluder measuring 25 mm in diameter (n=49) or an Amplatzer PFO
      occluder measuring 35 mm in diameter (n=6) was used. Complete occlusion by color
      Doppler and transesophageal contrast echocardiography investigation was achieved
      in 96% at follow-up 3-6 months after implantation; only 2 patients had a trivial
      residual shunt at follow-up. Mean fluoroscopy time was 6.7 minutes (range: 1.7
      47.1), and in-hospital follow-up was uneventful except for 1 patient who
      developed a cardiac tamponade requiring uneventful and successful needle
      pericardiocentesis. At a mean follow-up of 19 months (range: 3-32) no recurrent
      embolic neurological events was observed. Transcatheter closure of PFO with
      Amplatzer PFO occluder devices is a safe and effective therapy for patients with
      previous paradoxical embolism and aneurysmatic or nonaneurysmatic PFO.
      Percutaneous closure is associated with a high success rate, low incidence of
      hospital complications, and freedom of cerebral ischemia events.

PMID- 15966922
TI  - Intense migraines secondary to percutaneous closure of atrial septal defects.
AB  - In this study we evaluated the development of migraine after percutaneous closure
      of atrial septal defect. An abrupt and excruciating form of migraine developed
      shortly after shunt closure in 5 of 13 consecutive patients undergoing this
      procedure. A dramatic relief of pain was achieved almost instantaneously after
      administration of 300 mg of clopidogrel.

PMID- 15966923
TI  - Cardiac device implant wound closure with 2-octyl cyanoacrylate.
AB  - 2-Octyl Cyanoacrylate (2-OCA) is a tissue adhesive developed for skin laceration
      closure that has not been previously evaluated for cardiac device implant wound
      closure. We reviewed 460 consecutive device implants with 475 incisions between
      November 1993 and May 2001. From November 1993 to December 1998, all patients (n
      335) had a 3-layer reabsorbable suture closure with the application of topical
      bacitracin and dressing material. They were advised to avoid exposure to moisture
      for 10 days. From January 1999 to May 2001, the superficial suture layer was
      replaced with 2-OCA (n=125). No topical bacitracin or dressing was applied and
      patients were allowed to shower within 72 hours. The two groups did not differ
      significantly with respect to age (69 +/- 12 vs 70 +/- 13 years, P=NS), sex (59%
      vs 62% male, p=NS) or device type (77% vs 68% pacemakers/loop recorders, p=NS).
      All incisions were evaluated at 24 hours, 7-14 days, and 6-12 weeks
      postprocedure. The 2-OCA and suture groups did not differ significantly with
      respect to allergic reaction (0% vs 1.4%, P=NS), cellulitis (0% vs 0.9%, P=NS),
      and infection requiring explant (0.8% vs 0.3%, P=NS), respectively. Total adverse
      events occurred in 1 of 125 (0.8%) of the 2-OCA group versus 9 of 350 (2.6%) of
      the suture group (P=NS). In cardiac device implant closure 2-OCA obviated the
      need for topical antibiotics and dressing materials while facilitating wound care
      without increased complications.

PMID- 15966924
TI  - Use of a new thrombus extraction catheter (the Pronto) in the treatment of acute
      myocardial infarction.
AB  - The finding of an intracoronary thrombus at the time of coronary angiography is
      common in patients presenting with an acute coronary syndrome. Pharmacologic and
      mechanical treatment strategies have been developed and reported to facilitate
      the treatment of the thrombus along with a percutaneous coronary intervention. We
      report a case in which a Pronto thrombectomy catheter was utilized to facilitate
      thrombus removal prior to the placement of a coronary stent in a patient who
      developed postinfarct angina and pulmonary edema after successful thrombolytic
      therapy for a acute ST segment elevation myocardial infarction.

PMID- 15966925
TI  - Large left ventricular pseudoaneurysm presenting 25 years after penetrating chest
      trauma.
AB  - Penetrating chest wounds leading to damage of thoracic structures are common. A
      rare sequelae of chest trauma is a contained rupture of the left ventricle of the
      heart leading to the development of a pseudoaneurysm. This complication needs
      prompt recognition and repair because of the high likelihood of rupture and
      death. We report the case of a 47-year-old man who underwent repair of a stab
      wound to the heart 25 years ago and subsequently developed a large left
      ventricular pseudoaneurysm and presented with angina.

PMID- 15966926
TI  - Percutaneous coronary intervention to anomalous right coronary artery and
      retained piece of guidewire in the coronary vasculature.
AB  - The incidence of anomalous origin of the coronary arteries varies between 0.2%
      and 1.2%; the anomalous right coronary artery accounting for 6--27% of all the
      cases. To date technical experience on angioplasty in patients with anomalous
      coronary arteries reported in the literature is limited. A major factor is the
      selection of the guiding catheter to access the anomalous origin and also to give
      good support during angioplasty. We report the details of angioplasty in a
      patient with a similar problem and the dilemma following a fractured segment of
      the guidewire retained in the coronary vasculature.

PMID- 15966927
TI  - 32P brachytherapy in the treatment of complex Cypher in-stent restenosis.
AB  - Treatment of in-stent restenosis after implantation of a drug-eluting stent is a
      critical issue. We provide the first report of the use of intravascular radiation
      therapy for this purpose in a 73-year-old diabetic patient stented for small
      vessel bifurcation; treatment of Cypher diffuse in-stent restenosis with (32)P
      brachytherapy proved successful at clinical and angiographic follow-up at 7
      months. This finding should encourage systematic studies on the safety and
      efficacy of IRT in this problematic setting.

PMID- 15966930
TI  - Quantification of annular dilatation and papillary muscle separation in
      functional mitral regurgitation: role of anterior mitral leaflet length as
      reference.
AB  - BACKGROUND: We hypothesized that anterior mitral leaflet length (ALL) does not
      differ significantly between normal subjects and patients with functional mitral
      regurgitation (FMR) and hence may be used as a reference measurement to quantify
      annular dilatation and papillary muscle separation. METHODS AND RESULTS: We
      prospectively studied 50 controls, 15 patients with systolic left ventricular
      dysfunction (LVD) with significant FMR, and 15 patients with LVD without
      significant FMR. Significant MR was defined as an effective regurgitant orifice
      area > or = 0.2 cm2 as measured by the flow convergence method. Annular diameter,
      interpapillary distance, and ALL were measured, and the following ratios were
      derived: annular diameter indexed to ALL (ADI) and interpapillary distance
      indexed to ALL (IPDI). There was no significant difference in ALL among the three
      groups. The mean ADI was 1.26 times controls in patients with LVD without
      significant FMR compared to 1.33 times controls in patients with LVD with
      significant FMR (P = 0.06, no significant difference between groups). The mean
      IPDI was 1.42 times controls in patients with LVD without significant FMR
      compared to 2.1 times controls in patients with LVD with significant FMR (P <
      0.0001, significant difference between groups). CONCLUSION: There was no
      significant difference in ALL between controls and patients with LVD. ALL can be
      used as a reference measurement to quantify annular dilatation and papillary
      muscle separation in patients with FMR. Interpapillary distance but not annular
      diameter indexed to ALL correlates with severity of FMR.

PMID- 15966931
TI  - Serum N-terminal pro-BNP levels correlate with symptoms and echocardiographic
      findings in patients with mitral stenosis.
AB  - This study is designed to evaluate the N-terminal pro-BNP (NTproBNP) levels in
      patients with mitral stenosis (MS) and its possible correlation with clinical and
      echocardiographic parameters of the disease. The study group consisted of 29
      patients with isolated MS (patients with greater mild regurgitation were
      excluded) and 20 normal control subjects of similar age and gender distribution.
      Blood samples for NTproBNP were collected at the time of clinical and
      echocardiographic examination. NTproBNP levels were elevated in patients with MS
      compared to controls (325 +/- 249 pg/dL [19.9-890] versus 43 +/- 36 pg/dL [5.76
      193.3], P < 0.001). Patients with atrial fibrillation had significantly higher
      NTproBNP levels compared to those with sinus rhythm (561 +/- 281 pg/dL versus 254
      +/- 194 pg/dL, P = 0.044). MS patients with sinus rhythm also had higher NTproBNP
      levels compared to controls (254 +/- 194 pg/dL versus 43 +/- 36 pg/dL, P =
      0.00011). NT pro BNP levels correlated to the LA (R = 0.73, P < 0.0001) and RV (R
      = 0.41, P = 0.042) diameters, mitral valve area (R =-0.45, P = 0.025), mean
      mitral gradient (R = 0.57, P = 0.003), peak PAP (R = 0.7, P = 0.03), and NYHA
      functional class (R = 0.61, P = 0.007). In conclusion, serum NTproBNP levels
      correlate well with echocardiographic findings and functional class in patients
      with MS and can be used as a marker of disease severity. Additionally, it may
      have a potential use as an additional noninvasive and relatively cheap method in
      monitoring disease progression especially in patients with poor echocardiographic
      windows.

PMID- 15966932
TI  - Does coronary artery size really matter?
AB  - OBJECTIVE: To evaluate ischemia in right ventricle (RV) in patients with small
      caliber of right coronary artery (RCA). PATIENTS AND METHODS: The study
      population consisted of 60 consecutive patients undergoing coronary angiography
      within 3 months. The patients were divided into three different groups according
      to lumen diameter of RCA and coronary dominance. Group 1, 2, and 3 consisted of
      patients with small diameter of RCA, dominant RCA, and dominant circumflex
      artery, respectively. RV ischemia was assessed by using pulse-wave tissue Doppler
      sampling obtained from RV free wall close to the lateral tricuspid annulus at the
      apical four-chamber view during dobutamine stress echocardiography (DSE).
      RESULTS: When the mean systolic velocity percentages of increase from low to peak
      dose dobutamine in patients with small RCA were compared to those of other
      groups, statistically significant difference was found between group 1 and the
      other groups (P = 0.007 for group 1 vs group 2; P = 0.01 for group 1 vs group 3).
      The mean systolic velocity at peak dobutamine dose of patients with small caliber
      of right coronary artery was statistically lower than the other groups (P = 0.001
      for group 1 vs group 2, P < 0.001 group 1 vs group 3). CONCLUSIONS: There are a
      group of patients with small diameter of RCA causing probable ischemia in RV and
      small caliber of RCA can really matter in these patients.

PMID- 15966933
TI  - Diagnostic accuracy and prognostic value of dobutamine stress myocardial contrast
      echocardiography in patients with suspected acute coronary syndromes.
AB  - BACKGROUND: Both early stress testing and cardiac troponin I (cTnI) measurements
      are useful in assessing the prognosis of patients with acute coronary syndrome
      (ACS). We sought to determine the accuracy and prognostic value of wall motion
      analysis (WMA) and myocardial perfusion analysis (MPA) with real-time myocardial
      contrast echocardiography (RTMCE) during dobutamine stress in this patient
      population. METHODS: We performed dobutamine stress RTMCE to assess perfusion in
      158 consecutive patients (mean age: 61 +/- 13 years) with chest pain and possible
      ACS. Of these, 119 had normal cTnI, while 39 had isolated elevations of cTnI
      (range: 0.5-9.0 ng/ml). Quantitative angiography was performed within 1 month of
      RTMCE in 61 patients. Patients were followed for 16 months (range: 6-46 months).
      Cardiac events included death, nonfatal myocardial infarction, recurrent unstable
      angina, or need for urgent revascularization. RESULTS: The sensitivity,
      specificity, and accuracy of MPA for detecting a >50% coronary stenosis were 92%,
      77%, and 88%, respectively, while they were 62%, 85%, and 67% for WMA. Three-year
      event-free survival was 87% in patients with negative WMA and MPA, 49% in those
      with positive WMA and MPA, and 51% in patients with negative WMA but positive
      MPA. Age-adjusted multivariate analysis demonstrated that the only independent
      predictors of cardiac events were a positive MPA (hazard ratio = 3.23; 95% CI =
      1.23-8.49) and male sex (hazard ratio = 3.29; 95% CI = 1.21-8.97). CONCLUSIONS:
      In patients suspected of having an ACS, RTMCE improved the accuracy of dobutamine
      stress echocardiography for detecting coronary artery disease, and was an
      independent predictor of outcome.

PMID- 15966934
TI  - Detection of functional recovery using low-dose dobutamine and myocardial
      contrast echocardiography after acute myocardial infarction treated with
      successful thrombolytic therapy.
AB  - OBJECTIVE: We studied the value of low-dose dobutamine stress echocardiography
      (LDDE) and myocardial contrast echocardiography (MCE) in early prediction of left
      ventricular functional recovery (LVFR) after acute myocardial infarction (AMI)
      treated with successful thrombolysis. DESIGN: LDDE and MCE using second-harmonic
      intermittent imaging were performed in first week after AMI. LVFR was defined as
      an absolute > or =5% increase in ejection fraction, from early to 6 months of
      follow-up by Technetium-99m-Sestamibi single-photon emission computed tomography.
      PATIENTS: Out of 50 patients studied, 19 evolved with LVFR (group 1) and 31
      without LVFR (group 2). Regional dysfunction was detected in 103 (37%) infarcted
      related segments in group 1 and in 173 (63%) segments in group 2. RESULTS:
      Sensitivity, specificity, positive, and negative predictive values and accuracy
      for detecting LVFR by LDDE were 94.7% (18/19), 87.1% (27/31), 81.8% (18/22),
      96.4% (27/28), and 90% (45/50), respectively, and by MCE were 94.7% (18/19),
      51.6% (16/31), 54.5% (18/33), 94.1% (16/17), and 68% (34/50). In group 1,
      functional improvement was observed in 86.9% (53/61) of segments with contractile
      reserve by LDDE and in 65.8% (52/79) of segments with microvascular perfusion by
      MCE. In group 2, functional improvement was observed in 78.3% (18/23) of segments
      with contractile reserve by LDDE and in 25.5% (25/98) of segments with
      microvascular perfusion by MCE. All segments without perfusion by MCE evolved
      without functional recovery. CONCLUSION: LDDE was an accurate predictor of late
      left ventricular function recovery after AMI, while MCE was sensitive and has a
      high negative predictive value demonstrating that microvascular perfusion is
      essential for LVFR.

PMID- 15966935
TI  - Effect of microbubble exposure to ultrasound on quantitation of myocardial
      perfusion.
AB  - BACKGROUND: The purpose of this study was to determine whether acoustic
      disruption of microbubbles in the left ventricular (LV) cavity prior to entry in
      the coronary circulation or their gradual destruction in the myocardium during
      myocardial contrast echocardiography (MCE) affects quantitative parameters of
      myocardial perfusion. METHODS: MCE was performed in 12 open chest dogs with both
      intermittent high-power imaging (IHPI) and real-time low-power imaging (RLPI). To
      assess the affects of microbubble destruction in the LV cavity, MCE parameters of
      myocardial perfusion were compared for imaging planes that included versus
      avoided the LV cavity. To assess the effects of gradual disruption of
      microbubbles in the microcirculation during RLPI, MCE parameters from frames
      acquired continuously were compared to that from acquiring only end-systolic
      frames. RESULTS: Destruction of microbubbles in the LV cavity did not alter
      perfusion data for either form of imaging unless RLPI was performed using long (6
      frame) destructive pulse sequences. With RLPI, a gradual decay in microbubble
      signal occurred during their myocardial transit, the degree of which was related
      to the acoustic power. Signal decay during microbubble transit resulted in an
      overestimation of the microvascular blood velocity (beta-value) and an
      underestimation of the microvascular blood volume (A-value). CONCLUSIONS: MCE
      parameters of perfusion at low power can be significantly altered by microbubble
      destruction in the LV cavity and in the myocardial microcirculation during RLPI.
      Short microbubble destruction pulse sequences and imaging only at end-systole can
      reduce these effects.

PMID- 15966936
TI  - Caseous calcification of the mitral annulus: unusual case of spontaneous
      resolution.
AB  - Mitral annular calcification (MAC) is a common echocardiographic finding. Caseous
      calcification is a rare variant appearing as a round, tumor-like mass with
      central echolucent area located in the periannular region. Although occasionally
      misdiagnosed as a tumor and submitted to exploratory cardiotomy, this lesion
      appears to carry a benign prognosis. The true significance of caseous
      calcification is unknown; it might be an early and reversible stage of MAC or an
      atheroma-like lesion. We describe a case of caseous calcification with
      spontaneous resolution in a 60-year-old woman-such a finding should be considered
      in the differential diagnosis of intracardiac masses.

PMID- 15966937
TI  - An unusual case of recurrent mass in the right atrium: intravenous
      leiomyomatosis.
AB  - Intravenous leiomyomatosis with a cardiac extension is an extremely rare
      condition. In this report, a case of a 43-year-old female patient is described:
      she was operated for right atrial mass protruding into the inferior vena cava,
      which was later diagnosed as leiomyoma. After a 3-year symptom-free period,
      recurrence of the extension through the inferior vena cava was observed. After
      abdominal ultrasonographic examination, which revealed bilateral ovarian and
      retroperitoneal mass, bilateral oopherectomy, retroperitoneal, and right atrial
      mass excision was done. The retroperitoneal and right atrial mass was reported as
      leiomyoma. On her last admission, she had complaints of dizziness, abdominal
      pain, and bilateral leg edema; and right atrial mass extending through the common
      iliac vein was noted, but the patient did not accept any further treatment
      modality.

PMID- 15966938
TI  - Clinical and echocardiographic aspects of mid-ventricular hypertrophic
      cardiomyopathy.
AB  - Three cases of patients with hypertropic cardiomyopathy, apical aneurysm, and mid
      ventricular obstruction are presented. Two patients were diagnosed first by two
      dimensional and Doppler echocardiography, which showed mid-ventricular
      obliteration, characteristic hourglass image, and paradoxic jet flow. One patient
      with suboptimal echocardiogram was necessary to perform contrast echocardiogram.
      Clinical picture was characterized by angina and dyspnea. Thallium myocardial
      imaging revealed perfusion abnormalities in apical region, ischemia or necrosis.
      Cardiac catheterism showed mid-ventricular obliteration and significant
      intraventricular gradient and coronary arteries angiography without lesions.

PMID- 15966939
TI  - Myocardial postsystolic motion in ischemic and not ischemic myocardium: the
      clinical value of tissue Doppler.
AB  - Postsystolic motion (PSM) is a delayed ejection motion of the myocardium
      occurring after the aortic valve closure, during a generally prolonged isovolumic
      relaxation time (IVRT). In this review we analyze the physiopathologic mechanisms
      underlying PSM and the contribution of tissue Doppler for its understanding. By
      using various techniques, this phenomenon has been described in experimental
      observations and related to myocardial ischemia produced by gradual or abrupt
      coronary occlusion. In clinical studies, it is associated with recovery of
      regional myocardial function. Tissue Doppler, providing a velocity map of
      myocardial motion, allows an easy, noninvasive detection of PSM in the clinical
      setting. PSM, as identified by tissue Doppler, appears a hallmark of myocardial
      ischemia and viability but it may occur also in nonischemic conditions as left
      ventricular (LV) hypertrophy and volume overload, left bundle branch block and
      even in normal individuals. Strain and strain rate (SR), obtainable by off-line
      color tissue Doppler, may be useful to identify the mechanisms underlying PSM
      since these measurements reflect, respectively, the intrinsic rate and the
      percentage of deformation of a given myocardial segment, and are relatively
      independent of both overall cardiac movement and tethering of the neighboring LV
      segments. By using SR imaging, the ratio of PSM to regional systolic longitudinal
      strain can be used to separate ischemic from nonischemic PSM and appears the best
      quantitative parameter to identify ischemia during dobutamine stress. A method to
      detect LV wall asynchrony and immediate benefit of cardiac resynchronization
      therapy has been developed combining the assessment of tissue-tracking (TT)
      derived delayed longitudinal contraction and of SR-derived PSM.

PMID- 15966940
TI  - Transesophageal two-dimensional echocardiographic identification of hiatal
      hernia.
AB  - We report a case of a middle-aged woman in whom a transesophageal echocardiogram
      showed a mass-like lesion posteriorly near the descending thoracic aorta. We were
      able to make a definitive diagnosis of this mass as a hiatal hernia because of a
      thick inner lining measuring 6-9 mm in thickness similar to the stomach mucosa,
      and the presence of a few microbubbles within the mass. In addition, the
      microbubbles increased considerably after 10 cc of agitated normal saline flush
      via a nasogastric tube.

PMID- 15966941
TI  - Cardiac papillary fibroelastoma-a volatile variant.

PMID- 15966942
TI  - Echocardiographic diagnosis of malignant mesothelioma involving the pericardium.

PMID- 15966943
TI  - Doppler aliasing.

PMID- 15966944
TI  - Update on echocardiography of the inferior vena cava.

PMID- 15966946
TI  - The power of rage.

PMID- 15966947
TI  - Parenting skills training: an effective intervention for internalizing symptoms
      in younger children?
AB  - PROBLEM: A number of interventions are effective in treating older children with
      internalizing symptoms. However, little is known about the efficacy of
      psychological interventions in treating younger children. This study examined the
      impact on internalizing symptoms of a parenting skills training program. METHODS:
      Forty-three parents took part in a parenting skills training program.
      Externalizing and internalizing behaviors were measured before and after
      treatment and after a 6-month period. FINDINGS: Externalizing symptoms fell after
      treatment. Interestingly, internalizing scores fell to an approximately
      equivalent degree. CONCLUSIONS: An intervention targeted towards parenting may be
      efficacious in the treatment of children's internalizing symptoms.

PMID- 15966948
TI  - Accessing self-development through narrative approaches in child and adolescent
      psychotherapy.
AB  - TOPIC: Narrative psychotherapy with children and adolescents. PURPOSE: To
      demonstrate the integration of developmental theory with narrative approaches to
      psychotherapy as a means of accessing self-development during childhood and
      adolescence. SOURCES: Published literature and the author's experience in using
      narrative therapy with an 8-year-old and his foster mother. CONCLUSIONS: When
      informed by developmental theory, narrative approaches can be used effectively
      with children and adolescents to assist them in constructing positive life
      stories that can influence their identity formation.

PMID- 15966949
TI  - Decreasing the risk of complicated bereavement and future psychiatric disorders
      in children.
AB  - TOPIC: Decreasing the risk of complicated bereavement and future psychiatric
      disorders in children. PURPOSE: This literature will determine what major factors
      influence a child's response to death and to understand how children react to the
      death of a parent at different developmental stages. It will evaluate the
      following: a) What are children's emotional responses to the death of a parent?
      b) How can a surviving parent help the grieving child complete the tasks of
      grieving? c) What skills are important for a parent to learn in order to help the
      grieving child through the tasks of grieving and d) How can mental health
      providers help the grieving family and the grieving child? SOURCES: Relevant
      literature from child psychiatry, child psychology, and nursing. CONCLUSIONS: The
      death of a parent is a major stressful event for children and their families.
      This traumatic event can bring serious psychological and social distress to
      bereaved children and their families. Children who are not supported in the early
      phases of grieving can develop serious emotional and behavioral problems that can
      lead to the development of some major psychiatric disorders. Providing early
      prevention support programs for surviving parents and bereaved children can help
      both the parents and the children adapt to their losses. These structured
      programs can decrease the risk of complicated grief in bereaved families. More
      research studies are needed to validate the effectiveness of these early
      prevention program interventions.

PMID- 15966950
TI  - Child and adolescent mental health services in the UK: nurse consultants.
AB  - TOPIC: Children's mental health services in the UK are transforming. Innovations
      in health, social welfare, education, and youth justice agencies have all got
      emotional literacy at their core. The changing face of children's services has
      called for partnerships and new ways of planning and delivering services in
      statutory and voluntary sectors. Alongside this, nursing is evolving and
      developing new ways to meet the challenges that modernization brings. Nurse
      consultants are children's champions who have a leading role in helping lead
      children's services into the 21st century. PURPOSE: The following article
      explores the role of nurse consultants in child and adolescent mental health
      services (CAMHS).

PMID- 15966951
TI  - Make sure the voices for children are not lost on the federal scene.

PMID- 15966952
TI  - The use of selective serotonin reuptake inhibitors in children and adolescents
      with major depression.
AB  - TOPIC: Recent warnings about suicidal thoughts and self-injurious behavior in
      youth treated with selective serotonin reuptake inhibitors raise fundamental
      questions about the risk-benefit ratio of this class of medications. METHODS:
      Data from placebo-controlled trials are used to elucidate the potential risks and
      benefits of the selective serotonin reuptake inhibitors (SSRIs) in children and
      adolescent with major depression. This analysis forms the basis of clinical
      recommendations. SOURCES: The review includes the six large-scale, placebo
      controlled trials that have been published over the past decade. These data were
      augmented by information from regulatory hearings in 2003-2004 and selected open
      label reports. CONCLUSIONS: Emerging data from several clinical trials show that
      the SSRIs have modest effects on childhood depression. In addition, SSRI
      treatment may be associated with behavioral activation, self-harm, and suicidal
      ideation. Appropriate use of SSRIs in children and adolescents requires careful
      diagnostic assessment, evaluation of co-occurring conditions, and diligent
      monitoring, especially within the first weeks of treatment.

PMID- 15966954
TI  - The development of a new measure for the assessment of psychopathology in adults
      with intellectual disability.
AB  - BACKGROUND: People with intellectual disability (ID) and untreated psychiatric
      disorder lead unnecessarily difficult and unhappy lives. The prevalence of mental
      illness in children and adults with ID is greater than that found in the general
      population. A carer-completed checklist of psychopathology that could be used
      with both children and adults would help identify those individuals with ID most
      likely to have a mental health problem, help ensure that they receive the limited
      services that are usually available and also assist the process of clinical
      assessment, diagnosis and management. METHOD: This research aimed to develop a
      reliable and valid carer-completed checklist of psychopathology for adults with
      ID by redeveloping an existing measure for children with ID, the Developmental
      Behaviour Checklist (DBC-P). The new checklist, The Developmental Behaviour
      Checklist for Adults (DBC-A) was devised by changing, deleting and adding to DBC
      P items. Reliability studies were conducted with paid and family carers, and DBC
      A scores were compared with the results from two other measures of
      psychopathology. RESULTS: One DBC-P item was deleted, seven items changed and 12
      items added. The psychometric properties of this new checklist, the DBC for
      Adults with ID (DBC-A), were investigated and found to be satisfactory.
      Intraclass correlations for test-retest and inter-rater reliability ranged from
      0.72 to 0.85, and concurrent validity with two measures of emotional and
      behavioural disturbance was satisfactory. CONCLUSIONS: The carer-completed DBC-A
      provides a broad and comprehensive survey of the emotional and behavioural
      problems of adults with ID. It has satisfactory psychometric properties and
      therefore can be used with confidence in clinical, research and service settings,
      and its development allows continuous assessment of psychopathology across the
      lifespan for all people with ID.

PMID- 15966955
TI  - Cognitive variables and depressed mood in adults with intellectual disability.
AB  - BACKGROUND: Cognitive theory forms the foundation for cognitive therapy. There
      has been little research on cognitive theories and cognitive variables associated
      with depression in individuals with intellectual disability (ID). The current
      study examined cognitive variables of automatic thoughts, cognitive triad,
      hopelessness, attributions and self-esteem associated with two cognitive theories
      of depression: Beck's Cognitive Triad theory and the Hopelessness theory of
      depression. METHODS: Seventy-three adults with ID screened for adequate receptive
      vocabulary were interviewed as part of a larger study. They reported on cognitive
      constructs relating to depressed mood. In addition, comparisons were made between
      12 adults with ID and diagnosed major depression and a matched group of 12 adults
      with ID and no psychiatric diagnoses in order to determine if these groups
      differed on the cognitive constructs associated with the two cognitive theories
      of depression. RESULTS: The cognitive variables examined were all significantly
      correlated with depressed mood in the direction predicted by their respective
      cognitive theory. Internal consistencies were good or excellent for most
      instruments, with the exception of those measuring hopelessness and attributions.
      In addition, significant differences were obtained between groups of individuals
      with and without co-morbid major depression on all variables except for
      hopelessness. CONCLUSIONS: The results indicate that adults with ID screened for
      adequate receptive vocabulary are capable of reporting on subjective feelings of
      depressed mood and associated cognition constructs. The instruments used may be
      suitable for this population as they generally possessed sound internal
      consistencies. The results support the further examination of cognitive theories
      of depression among individuals with ID in order to assess the appropriateness of
      cognitive therapies for this population. Discrepant findings regarding
      hopelessness are discussed.

PMID- 15966956
TI  - The reliability and validity of general psychotic rating scales with people with
      mild and moderate intellectual disabilities: an empirical investigation.
AB  - BACKGROUND: Whilst assessment tools have been developed to diagnose schizophrenia
      in people with mild intellectual disabilities (IDs), little attention has been
      paid to developing reliable and valid dimensional measures of psychotic
      experiences with this population. This study investigates the reliability and
      validity of two such measures developed for the general adult psychiatric
      population, the Positive and Negative Syndrome Scale (PANSS) and the Psychotic
      Symptom Rating Scales (PSYRATS), with a population of adults with mild IDs.
      METHOD: Sixty-two adults with mild IDs were interviewed using the PANSS and
      PSYRATS, and independently interviewed using the Psychiatric Assessment Schedule-
      Adults with Developmental Disability (PAS-ADD) to obtain psychiatric diagnoses to
      the criteria of the International Classification of Diseases--Tenth Revision (ICD
      10). On the basis of ICD-10 diagnosis, participants were divided into three
      groups: psychosis (n=11); other mental health problem (n=14); no mental health
      problem (n=37). PANSS and PSYRATS subscale scores were compared across these
      three groups and were correlated with PAS-ADD symptom scores across a number of
      PAS-ADD symptom domains. RESULTS: All PANSS and PSYRATS subscales showed adequate
      internal reliability, largely good test-retest reliability, and logical inter
      correlations between subscales. The PANSS positive symptoms and the PSYRATS
      auditory hallucinations subscales differentiated between the psychosis group and
      the other groups; the PANSS general symptoms subscale differentiated between the
      psychosis and no mental health problem groups; and the PANSS negative symptoms
      and the PSYRATS delusions subscales did not differentiate between the three
      groups. CONCLUSIONS: The PANSS and PSYRATS are promising measures for use with
      people with mild IDs and psychotic experiences, although further investigation of
      items relating to negative symptoms and delusions is warranted.

PMID- 15966957
TI  - Correlates of restraint use in an institutional population: a replication.
AB  - BACKGROUND: Reducing inappropriate restraint is an important mission of services
      for people with intellectual disabilities (IDs). METHODS: In this study, 52
      clients who had been restrained were compared with 52 other clients, individually
      matched on age, gender and level of IDs. Participants were mostly adults with
      severe and profound IDs in an institutional setting. RESULTS: The two groups
      differed on six Diagnostic Assessment for the Severely Handicapped-II (DASH-II)
      and three Aberrant Behaviour Checklist (ABC) scales. However, discriminant
      functional analysis demonstrated that only DASH-II Impulse control disorder and
      ABC Irritability and Elimination disorder scores predicted group membership but
      only moderately. CONCLUSIONS: Individual differences in maladaptive behaviours
      were only moderately predictive of restraint use.

PMID- 15966958
TI  - Randomized controlled trial of assertive community treatment in intellectual
      disability: the TACTILD study.
AB  - BACKGROUND: There has been a policy shift away from hospital to community in the
      services of all those with psychiatric disorders, including those with
      intellectual disability (ID), in the last 50 years. This has been accompanied
      recently by the growth of assertive outreach services, but these have not been
      evaluated in ID services. METHOD: In a randomized controlled trial we compared
      assertive outreach with 'standard' community care, using global assessment of
      function (GAF) as the primary outcome measure, and burden and quality of life as
      secondary measures. RESULTS: We recruited 30 patients, considerably less than
      expected; no significant differences were found between the primary and secondary
      outcomes in the two groups. The differences were so small that a Type II error
      was unlikely. CONCLUSIONS: Reasons for this lack of specific efficacy of the
      assertive approach are discussed and it is suggested that there is a blurring of
      the differences between standard and assertive approaches in practice.

PMID- 15966959
TI  - An exploratory study of assertive community treatment for people with
      intellectual disability and psychiatric disorders: conceptual, clinical, and
      service issues.
AB  - BACKGROUND: Assertive community treatment (ACT) has been applied to a number of
      disorders in the adult population, such as schizophrenia, with some degree of
      success; its use in the treatment of people with intellectual disability (ID) and
      mental illness has received little attention. Despite the high costs of ID in
      health and social care, there has been very little evidence-based practice for
      people with ID and mental illness, and it remains a neglected area of research.
      Aims The aims of this study were an exploratory comparison of the effectiveness
      of an ACT model for the treatment of mental illness in people with ID (ACT-ID)
      with a standard community treatment (SCT-ID) approach. METHOD: A Randomized
      controlled trial design was adopted and allocation was made by stratified
      randomization by an independent statistician. The prognostic factors used in the
      randomization were gender and psychiatric diagnosis (psychosis vs. affective).
      Service users were randomly allocated to either ACT-ID or SCT-ID. RESULTS: There
      were no statistically significant differences between ACT-ID and SCT-ID in terms
      of the level of unmet needs, carer burden, functioning and quality of life, but
      borderline evidence of a difference between treatment groups in quality of life
      in favour of SCT-ID. Both SCT-ID and ACT-ID groups decreased level of unmet needs
      and carer burden, and increased functioning. SCT-ID also led to a small increase
      in quality of life.

PMID- 15966960
TI  - Careers of offenders with an intellectual disability: the probabilities of
      rearrest.
AB  - BACKGROUND This paper reports results from a total population of persons with
      intellectual disabilities (ID) in Western Australia arrested for the first time
      since 1 April 1984. It is part of a longitudinal study that 'tracked' offenders
      with ID through the criminal justice system over an 11-year period to compare
      their experiences at each stage of the justice process with a sample of the
      general offending population. The research draws on an analysis of the Western
      Australian Police Services Apprehension records and the Disability Services
      Commission database. METHOD The data collected provided the opportunity to
      calculate base rates of the probability of rearrest of offenders with ID in
      comparison to mainstream offenders. RESULTS The study found that people with ID
      had a significantly higher rate of rearrest than general population offenders and
      the study canvasses some possible reasons for this finding.

PMID- 15966961
TI  - A review of the emotional, psychiatric and behavioural responses to bereavement
      in people with intellectual disabilities.
AB  - BACKGROUND: Our knowledge and understanding of grief and its consequences have
      grown rapidly in recent years. There is a growing understanding that bereavement
      and loss represent a very significant event in the lives of people with
      intellectual disabilities (IDs). To date, there is no systematic review of the
      literature on the emotional, psychiatric and behavioural responses to bereavement
      in people with IDs. METHOD: This comprehensive literature review firstly examines
      the current opinion regarding the phenomenology of pathological grief in the
      general population. Research examining the ability of people with IDs to
      understand the concept of death is explored. In addition, a systematic review of
      the literature looking at the emotional, behavioural and psychiatric responses to
      bereavement is carried out. RESULTS: Bereavement and loss have distinct effects
      on the mental health, behaviour and emotional lives of people with IDs. Following
      a bereavement, symptoms of depression and anxiety increase, and general behaviour
      is altered. Traumatic grief symptoms have not yet been specifically studied and
      quantified. CONCLUSIONS: Particular difficulties are associated with researching
      the effects of bereavement on people with IDs. Further work needs to be done to
      more accurately describe the nature, time-scale, severity and frequency of the
      symptoms of traumatic grief in people with IDs, in order to improve assessment
      and treatment of affected individuals.

PMID- 15966962
TI  - Knowing you: the interpersonal perceptions of staff towards aggressive
      individuals with mild to moderate intellectual disabilities in situations of
      conflict.
AB  - OBJECTIVES: Staff attributions concerning challenging behaviour have been found
      to play a role in determining their responses. The emphasis in the literature has
      been on staff beliefs about the challenging behaviour itself. However, staff are
      also likely to be responding to the person engaging in the behaviour. The aim of
      this study was to explore workers' perceptions of individuals who are frequently
      aggressive. DESIGN AND METHODS: Thirty-six staff members working with individuals
      presenting problems of frequent aggression participated in this study. They were
      interviewed about an incident of aggression involving the person they worked
      with. The semi-structured interview, based on a Rational Emotive Therapy format,
      aimed to tap into the emotions aroused in the staff members and interpersonal
      appraisals that they made at the time of the incident. The responses were content
      analyzed. RESULTS: The strength of the staff member's emotional reactions were
      noteworthy. Furthermore, approximately half of the staff members believed that
      the clients' aggression was directed at them personally. In turn, the majority of
      staff members described their clients in negative terms, and said that their
      first impulse had been to confront the clients. CONCLUSIONS: The findings suggest
      that interpersonal perceptions may have a role in determining staff responses to
      individuals who behave aggressively. The clinical and theoretical implications of
      the findings were discussed, alongside directions for future research.

PMID- 15966963
TI  - Is Post-Traumatic Stress Disorder a helpful concept for adults with intellectual
      disability?
AB  - BACKGROUND: Research using the concept of Post-Traumatic Stress Disorder (PTSD)
      with adults with intellectual disability (ID)assumes they perceive and react to
      traumatic events in a similar way to non-disabled adults. Reactions to trauma
      displayed by children may be relevant to adults with ID as well. METHODS: Two
      focus groups were held with professionals and practitioners to explore the
      relevance of criteria from child as well as adult literature to adults with ID
      who experience trauma. Descriptive thematic analysis was carried out. RESULTS:
      Abuse, parental bereavement, and having children removed were considered common
      sources of trauma. Similarities identified between disabled and non-disabled
      adults were flashbacks and nightmares; distressed by reminders; avoidance;
      hypervigilance and increased arousal. Differences were the frequent occurrence of
      multiple rather than single events, which were considered significant in
      generating chronic problems similar to those described as PTSD; also the
      occurrence of physical health problems and behavioural re-enactments. DISCUSSION
      AND CONCLUSIONS: Experienced professionals and practitioners considered most of
      the ideas from PTSD research with non-disabled adults to be relevant to adults
      with ID who experience trauma, but that some behaviour reported in research with
      children was also relevant. Topics and questions for use in clinical and research
      practice with individuals who have experienced trauma were proposed.

PMID- 15966964
TI  - Health co-morbidities in ageing persons with Down syndrome and Alzheimer's
      dementia.
AB  - BACKGROUND: Consideration of the relationship between physical and mental health
      co-morbidities in ageing persons with Down syndrome (DS) and Alzheimer's dementia
      (AD) is of clinical importance both from a care and resource perspective. AIM To
      investigate and measure health co-morbidities in ageing persons with Down
      syndrome with and without AD. METHODS: Recorded physical and mental health needs
      were ascertained for 124 persons with DS>35 years through a systematic and
      detailed search of individual medical and nursing case records. Differences in
      persons with and without AD were investigated, by stage of dementia and by level
      of intellectual disability (ID). A summed score for health co-morbidities was
      created and compared using t-tests. RESULTS: Persons with AD had significantly
      higher co-morbidity scores than persons without AD (t=-8.992, d.f.=121,
      P<0.0001). There was also a significant difference in summed co-morbidity scores
      for persons at end-stage vs. persons at mid-stage AD (t=-6.429, d.f.=56,
      P<0.0001). No differences were found by level of ID. CONCLUSIONS: Increasing
      health co-morbidities in persons with DS and AD have important implications for
      care and resources. Appropriate environmental supports combined with competent
      skilled staff are crucial and will have an important impact on the quality of
      life for this increasingly at risk population.

PMID- 15966965
TI  - Clozapine treatment of psychosis associated with velo-cardio-facial syndrome:
      benefits and risks.
AB  - BACKGROUND: Clozapine is licensed for the treatment of psychotic illnesses
      resistant to other antipsychotic medications. Velo-cardio-facial syndrome (VCFS)
      is associated with a vulnerability to psychotic illness that may be resistant to
      treatment with conventional typical and atypical antipsychotics. PATIENTS AND
      METHODS: A 32-year-old man with intellectual disability (ID) and a long history
      of treatment-resistant psychosis was found to have VCFS. Treatment with typical
      antipsychotic drugs and with one atypical olanzapine produced no improvement.
      RESULTS: Treatment with clozapine produced an improvement in psychotic symptoms
      and associated behavioural abnormalities, but caused hypersalivation,
      constipation and a seizure disorder. The latter led to two fractures, one
      requiring surgery. The addition of sodium valproate stopped seizures.
      CONCLUSIONS: Clozapine may improve psychotic symptoms for people with ID
      associated with VCFS, but clinicians should be alert for potential adverse
      effects.

PMID- 15966968
TI  - Hyperbaric oxygen as an adjunctive treatment for zygomycosis.
AB  - Zygomycosis is a rare but emerging mycosis. Because of the sub-optimal efficacy
      of the standard antifungal treatment for this disease, hyperbaric oxygen (HBO)
      has been used occasionally as an adjunctive therapeutic modality. A review of 28
      published cases of zygomycosis indicates that adjunctive HBO may be beneficial in
      diabetic patients (94% survival), whereas its benefit in the small group of
      patients with haematological malignancies or bone marrow transplants is doubtful
      (33% survival; p 0.02). Prolonged courses of HBO were associated with a higher
      survival (100% survival; p 0.003). Additional studies are required to assess the
      optimal timing and dose for HBO treatment.

PMID- 15966969
TI  - The impact of early cytomegalovirus infection and disease in renal transplant
      recipients.
AB  - Human cytomegalovirus (HCMV) infection is the single most frequent infectious
      complication in the early period after kidney transplantation. The HCMV load in
      blood, measured by HCMV PCR or the HCMV pp65 antigen test, is a predictor of HCMV
      disease in seropositive recipients. However, plasma virus load measurements are
      of only modest value in predicting the risk of HCMV disease in seronegative
      recipients of kidneys from seropositive donors. HCMV infection is an independent
      risk-factor for acute kidney graft rejection. There is also evidence that HCMV is
      associated with an increased long-term mortality and post-transplant diabetes
      mellitus. Whether pre-emptive or prophylactic therapy should be the preferred
      strategy is not yet decided. Some studies indicate that HCMV prophylaxis may
      reduce the risk of acute rejection, and thereby increase long-term graft survival
      in seronegative recipients of kidneys from seropositive donors.

PMID- 15966970
TI  - Evaluation of hybridisation on oligonucleotide microarrays for analysis of drug
      resistant Mycobacterium tuberculosis.
AB  - A molecular approach was developed to identify drug-resistant strains of
      Mycobacterium tuberculosis by means of biochips with oligonucleotides immobilised
      in polyacrylamide gel pads. The technique was based on multiplex PCR, followed by
      hybridisation on an oligonucleotide microarray, and detected > 95% of rifampicin
      resistant and c. 80% of isoniazid-resistant M. tuberculosis isolates within 12 h.
      In total, 220 drug-resistant isolates and 131 clinical samples were tested using
      biochips. The sensitivity and specificity of the developed method were comparable
      with those of standard bacteriological testing of M. tuberculosis drug
      resistance.

PMID- 15966971
TI  - Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter
      baumannii: patient prognosis and risk-factors for colonisation and infection.
AB  - Between October 2001 and August 2002, 30 hospital patients became infected or
      colonised by a multiresistant (including to carbapenems) epidemic strain of
      Acinetobacter baumannii (AbMR) in a hospital outbreak. This study analysed the
      risk-factors associated with acquisition of this epidemic strain and investigated
      the prognosis of patients infected by AbMR, with the aim of elucidating factors
      which lead to mortality. A case-control study of the acquisition of AbMR in
      patients infected or colonised in the hospital outbreak was performed.
      Independent risk-factors leading to death were studied by logistic regression
      analysis. Multivariate analysis of the risk-factors for colonisation/infection
      with AbMR revealed an independent association with the presence of an arterial
      catheter (OR, 1.13; 95% CI, 1.03-1.25) and administration of imipenem as
      monotherapy (OR, 11.12; 95% CI, 2.33-53.09). Multivariate analysis of the
      prognostic features leading to mortality revealed a significant association with
      hypotension or shock (OR, 24.63; 95% CI, 1.56-387.56) at the time of bacterial
      isolation.

PMID- 15966972
TI  - Surveillance of chronic haemodialysis-associated infections in southern Israel.
AB  - During a 12-month surveillance period, haemodialysis (HD) patients in southern
      Israel were categorised according to the type of vascular access site (VAS),
      i.e., arteriovenous (AV) fistula, synthetic AV graft, and cuffed or non-cuffed
      vascular catheters. Endpoints, expressed as cases/100 patient-months, were:
      incidence of hospital admission; antibiotic therapy; bloodstream infection (BSI);
      and VAS infection. These were compared to Centers for Disease Control (CDC)
      surveillance data, overall and by VAS type. In total, 2568 patient-months were
      analysed. The VAS distribution differed significantly from CDC data for fistulas
      (72% vs. 31%), grafts (12% vs. 41%), cuffed catheters (11% vs. 25%) and non
      cuffed catheters (5% vs. 3%) (p < 0.0001 in all cases). Of 151 admissions, 32%
      resulted from infection, for which 112 antibiotic courses (22% vancomycin) were
      given. There were 16 BSIs, three involving resistant strains. The incidences of
      admission, antibiotic therapy, BSI and VAS infection were significantly lower
      overall, compared to CDC rates, as were most VAS-specific endpoints. These
      differences may be explained by VAS type distribution, although other factors may
      also be involved. Reporting regional or national surveillance data may allow a
      standardised comparison of the incidence of HD-associated infections.

PMID- 15966973
TI  - Comparative pathogenicity of bacteraemic isolates of Aeromonas hydrophila and
      Klebsiella pneumoniae.
AB  - Two bacteraemic isolates of Aeromonas hydrophila and Klebsiella pneumoniae, Ah
      2743 and Kp-129, respectively, were studied for their relative pathogenicity in
      comparison with Escherichia coli ATCC 25922. Ah-2743 caused significantly higher
      serum levels of tumour necrosis factor-alpha, interleukin (IL)-1beta or IL-6 in
      human whole blood, and higher serum IL-1beta and IL-6 levels in infected mice,
      than did Kp-129 and E. coli ATCC 25922. In addition, in BALB/c mice infected by
      intraperitoneal inoculation, Ah-2743 caused a higher fatality rate (80%) than did
      Kp-129 (0%). With intramuscular inoculation, Ah-2743 caused more rapid and
      intense local accumulation of inflammatory cells than did Kp-129, and myonecrosis
      was present only in Ah-2743-infected mice. These data indicate that Ah-2743 is
      more pathogenic than Kp-129 or E. coli ATCC 25922 for BALB/c mice. The cellular
      components or extracellular factors associated with increased cytokine induction
      and pathogenicity of A. hydrophila in mice merit further investigation.

PMID- 15966974
TI  - Investigation of hearing loss in patients with acute brucellosis by standard and
      high-frequency audiometry.
AB  - This study aimed to determine the effect of acute brucellosis on the auditory
      system. Forty-two patients with acute brucellosis were evaluated clinically, and
      with serological and audiological tests, before and after treatment. Hearing
      threshold averages were calculated at 11 different frequencies (250-8000 Hz) of
      the auditory airway, and statistical analysis was performed. The average hearing
      thresholds were > 20 dB, with standard audiometry at 6000-8000 Hz, and < 20 dB at
      all other frequencies. After treatment, the average auditory threshold decreased
      to < 20 dB at 6000-8000 Hz (p < 0.0001). Pure-tone hearing thresholds were
      improved at all frequencies after treatment, with statistically significant
      differences at all frequencies except 12,000, 14,000 and 16 000 Hz (p < 0.05).
      There was no permanent hearing loss caused by acute brucellosis, and hearing
      thresholds were restored after treatment. It was concluded that acute brucellosis
      affects the auditory system, especially at high frequencies, and that patients
      with all forms of brucellosis should be evaluated for hearing loss.

PMID- 15966975
TI  - Epidemiological considerations following long-term surveillance of invasive group
      A streptococcal disease in The Netherlands, 1992-2003.
AB  - A nationwide laboratory-based surveillance system for invasive group A
      streptococcal (GAS) infections was conducted in The Netherlands from March 1992
      until December 2003. Until 1996, all isolates submitted were evaluated clinically
      and demographically. During this period there was a transition from passive to
      active surveillance for some of the participating laboratories, corresponding to
      a national coverage of 50%. During active surveillance, participating
      laboratories submitted twice as many isolates from invasive GAS disease, whereas
      the relative submission of isolates representing very severe manifestations
      (toxic shock-like syndrome, fatality) did not increase. From 1997 onwards,
      invasiveness was defined solely on the basis of source of isolation (without
      clinical evaluation). During the period of microbiological and clinical
      evaluation, microbiological evaluation alone was found to be specific (> 99%),
      but had limited sensitivity (66%). Estimation of the true rate of invasive GAS
      disease should be based on an active surveillance system with inclusion of both
      microbiological and clinical data.

PMID- 15966976
TI  - Invasive group A, B, C and G streptococcal infections in Denmark 1999-2002:
      epidemiological and clinical aspects.
AB  - Group A streptococci (GAS) have been described frequently as an emerging cause of
      severe invasive infections in population-based surveillance studies, whereas the
      descriptions of group B, C and G streptococci (GBS, GCS and GGS) have been less
      frequent. Enhanced surveillance for invasive GAS, GBS, GCS and GGS was performed
      in Denmark in 1999-2002. A detailed questionnaire was completed for 1237 (98%) of
      1260 invasive infections. GAS infections dominated (40%), followed by GGS (32%),
      GBS (23%) and GCS (6%). Most (74%) patients had predisposing factors, and there
      were no significant differences between the four serogroups when comparing the
      prevalence of cancer, diabetes mellitus, chronic heart or lung diseases,
      immunodeficiency or alcohol abuse. The overall case fatality rate at day 30 was
      21%, increasing significantly to 59% for patients with streptococcal toxic shock
      syndrome (STSS). STSS was significantly more frequent in GAS patients (10%) than
      in GCS (4%), GBS (2%) and GGS (2%) patients. Regression analyses showed that,
      despite a younger median age among GAS patients, the probability of developing
      septic shock and mortality was significantly higher among GAS patients than among
      GBS and GGS patients. These analyses showed no significant differences between
      GAS and GCS infections. Invasive infections caused by GAS, GBS, GCS and GGS are
      still a major challenge for clinicians. Continued epidemiological and
      microbiological surveillance is important to assess the development of these
      infections and to improve preventative strategies.

PMID- 15966977
TI  - Group B streptococcal soft tissue infections in non-pregnant adults.
AB  - Skin and soft tissue infections are the most common presentations of invasive
      Streptococcus agalactiae infections. This study reviewed 71 patients in a medical
      centre in southern Taiwan with S. agalactiae soft tissue infections. The
      mortality rate was 7%, and 11% of patients lost their extremities following
      extensive tissue necrosis. Critical illness and the presence of cutaneous
      ulceration heralded a fatal prognosis. Risk-factors for amputation of limbs
      included advanced age, cutaneous ulceration and polymicrobial infection. It was
      concluded that invasive S. agalactiae soft tissue infections, as with infections
      caused by Streptococcus pyogenes, can also lead to substantial morbidity and
      mortality in non-pregnant adults.

PMID- 15966978
TI  - Prevalence of erythromycin and clindamycin resistance among Streptococcus
      agalactiae isolates in Germany.
AB  - The antimicrobial susceptibilities of 338 clinical Streptococcus agalactiae
      isolates from two geographical regions in Germany were determined by agar
      dilution. All isolates were susceptible to penicillin, cefotaxime and vancomycin.
      The overall frequencies of erythromycin and clindamycin resistance were 11% and
      4.7%, respectively. Determination of resistance phenotypes among the 37
      erythromycin-resistant isolates revealed constitutive and inducible MLS(B)
      resistance in 40.6% and 37.8% of isolates, respectively, and susceptibility to
      clindamycin in 21.6% of isolates. Only 14.3% of isolates with inducible MLS(B)
      resistance were identified as clindamycin-resistant by determination of
      clindamycin MICs. Pulsed-field gel electrophoresis suggested a clonal
      distribution pattern among the erythromycin-resistant isolates.

PMID- 15966979
TI  - Incidence of inducible clindamycin resistance in staphylococci: first results
      from Turkey.
AB  - In total, 408 staphylococcal isolates were tested for inducible clindamycin
      resistance (ICR) by the disk-diffusion induction test (D-test). ICR was detected
      in 5.7% of 105 methicillin-resistant Staphylococcus aureus (MRSA) isolates, 3.6%
      of 111 methicillin-susceptible S. aureus isolates, 30.8% of 94 methicillin
      resistant coagulase-negative staphylococcal (CoNS) isolates, and 11.2% of 98
      methicillin-sensitive CoNS isolates. All MRSA isolates that were erythromycin
      resistant and clindamycin-susceptible were positive by the D-test. The same
      results were obtained with an azithromycin instead of an erythromycin disk. All
      isolates were susceptible to quinupristin-dalfopristin. The cost-benefit of the d
      test should be evaluated locally after determining the incidence of the different
      resistance phenotypes.

PMID- 15966980
TI  - Methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin
      in a retrospective case series from 12 French hospital laboratories, 2000-2003.
AB  - A retrospective analysis of hospital laboratory databases for 2000-2003 found
      that 0.4-1.0% of methicillin-resistant Staphylococcus aureus isolates had an
      antibiotic susceptibility pattern associated previously with the production of
      Panton-Valentine leukocidin (PVL). Of 81 isolates of this type, 35 were available
      for molecular testing. Each of the 35 available isolates carried the PVL genes,
      and 33 of these 35 isolates had an identical SmaI pulsed-field gel
      electrophoresis pattern.

PMID- 15966981
TI  - Spread of novel expanded-spectrum beta-lactamases in Enterobacteriaceae in a
      university hospital in the Paris area, France.
AB  - In 2002, 28 non-duplicate enterobacterial isolates producing extended-spectrum
      beta-lactamases (ESBLs) were collected from infected patients at the Bicetre
      Hospital in Paris, France. Escherichia coli was the predominant ESBL-positive
      enterobacterial species, comprising ten (36%) of the isolates. CTX-M enzymes (CTX
      M-3, CTX-M-10, CTX-M-14 and CTX-M-15) were produced by 11 (39%) of the isolates
      (six E. coli, two Enterobacter cloacae, one Enterobacter aerogenes, one Proteus
      mirabilis and one Citrobacter freundii). Other ESBLs, such as VEB-1 and PER-1,
      were also detected, but less frequently.

PMID- 15966982
TI  - First description of DHA-1 ampCbeta-lactamase in Proteus mirabilis.
AB  - This report describes the first occurrence of the DHA-1 ampCbeta-lactamase gene
      in Proteus mirabilis. The organism was isolated from the vaginal flora of a
      pregnant woman in a French hospital. The DHA-1 beta-lactamase gene was identified
      on the basis of phenotypic characteristics, PCR amplification and sequencing.
      Antagonism between cefoxitin and the other cephalosporins suggested inducible
      production of the DHA-1 enzyme.

PMID- 15966983
TI  - Sensitivity of the Cobas Amplicor system for detection of Mycobacterium
      tuberculosis in respiratory and extrapulmonary specimens.
AB  - The Cobas Amplicor PCR system (CA-PCR) was compared with culture and staining for
      acid-fast bacilli (AFB) for the early detection of Mycobacterium tuberculosis in
      respiratory clinical specimens and otherwise normal sterile body fluids. The
      sensitivity, specificity and positive and negative predictive values of CA-PCR
      were determined with AFB-positive and AFB-negative specimens. The sensitivity of
      CA-PCR ranged from 73.6% to 100% for AFB-positive samples, while sputa collected
      after bronchoscopy were the most useful specimens, with 70% sensitivity and 98.6%
      specificity among the AFB-negative samples.

PMID- 15966984
TI  - Genomic diversity of Staphylococcus epidermidis isolates from the intensive care
      unit.

PMID- 15966986
TI  - Congress president's report: 3rd Slovenian Congress of Nephrology.

PMID- 15966987
TI  - Renal replacement therapy in Slovenia: 2003 annual report.
AB  - The total number of end-stage renal disease patients treated by renal replacement
      therapy increased from 1584 on 31 December 2002 to 1661 on 31 December 2003 (4.9%
      increase). Of these patients, 70.5% were treated by hemodialysis, 7.0% by
      peritoneal dialysis and 22.5% had a functioning renal graft. The patients were
      treated at 18 dialysis centers and one transplant center. The number of prevalent
      patients treated by renal replacement therapy per million of the population
      (p.m.p.) was 846 at the end of 2003. The number of incident (new) patients in
      2003 was 131 p.m.p. The gross mortality rate of dialysis patients was stable
      through the years of the study and reached 11.8% in 2003. 57.6% of new patients
      starting hemodialysis were > or = 65 years old and 23.2% were diabetics. Epoetin
      therapy was prescribed to 89.8% of dialysis patients. The number of patients
      positive for hepatitis B or hepatitis C viruses is stable and low (3.1% of all
      dialysis patients).

PMID- 15966988
TI  - Our experience with epoetins in treating renal anemia.
AB  - Epoetin treatment of renal anemia has been practiced in Slovenia since 1988. More
      than 90% of hemodialysis patients and 83% of peritoneal dialysis patients have
      been treated with epoetin. Epoetin has also been available for patients with
      renal anemia in the pre-dialysis period and for those with a failing kidney
      allograft. Although epoetin treatment did not accelerate the worsening of native
      kidney function or allograft function, intensified antihypertensive treatment was
      required in kidney graft recipients. In patients on peritoneal dialysis,
      hypervolemia had a greater effect on hypertension than did epoetin treatment.
      Epoetin resistance was connected with C-reactive peptide cryptorchidism, intact
      parathyroid hormone, and treatment with angiotensin-converting enzyme inhibitors.
      In hemodialysis patients, lower doses of epoetin were required for patients
      receiving low molecular heparin and those with lower iPTH. Epoetin alpha, epoetin
      beta and epoetin omega seemed to be effective and safe in the treatment of renal
      anemia. In the past 2 years, epoetins were administered to hemodialysis patients
      only intravenously.

PMID- 15966989
TI  - Cardiac troponin T in patients with kidney disease.
AB  - Atherosclerosis is accelerated in dialysis patients and cardiovascular mortality
      is up to 20 times higher than in the general population. Cardiac troponin T
      (cTnT) is a sensitive marker of myocardial necrosis and studies have confirmed
      the superiority of this marker over traditional cardiac enzymes. Elevated cTnT
      has been observed in patients with various degrees of renal failure and treatment
      modalities in the absence of an acute coronary event. The possibility that
      increased troponins reflect decreased clearance or analytical interference from
      uremic serum is unlikely. It is accepted that cTnT detected in serum from
      patients with end-stage renal failure is derived from myocytes and this effect
      could be caused by subclinical myocardial ischemic release of troponin,
      myocardial remodeling, or from uremic pericarditis or myocarditis. The
      significance of cTnT in patients with different degrees of renal failure and
      different treatment modalities is presented in this review.

PMID- 15966990
TI  - Cardiovascular calcification in patients with end-stage renal disease.
AB  - Vascular calcifications are very frequent extraosseous calcifications in patients
      with chronic renal disease. They occur in the intima and in the media. They are
      associated with decreased arterial elasticity and increased mortality. The risk
      factors are: advanced age, duration of dialysis treatment, diabetes, increased
      phosphate concentration, the dose of Ca-containing phosphate binders and
      inflammation. It is now well established that vascular smooth muscle cells
      actively take up phosphate to form bioapatite. This process is associated with a
      phenotypic transformation of vascular smooth muscle cells during which they
      express osteoblast markers. Lipids and inflammatory cytokines also increase
      bioapatite formation. Calcification inhibitors are matrix Gla protein and fetuin
      A. Decreased serum fetuin-A concentration is associated with a higher mortality
      rate in dialysis patients. An important preventive measure for vascular
      calcification is the substitution of Ca-containing by non-Ca-containing phosphate
      binders.

PMID- 15966991
TI  - Regular exercise as a part of treatment for patients with end-stage renal
      disease.
AB  - Physical inactivity and its negative influence on health and the quality of life
      is a common problem generally, especially in patients with chronic illness and
      also in patients with end-stage renal disease. Motivation for regular physical
      exercise could be a problem. A supervised outpatient program in a rehabilitation
      center, a home exercise rehabilitation program and an exercise rehabilitation
      program during the first hours of the hemodialysis treatment with a bed bicycle
      ergometer in the renal unit could be carried out. Low intensity aerobic activity
      has a favorable effect on cardiovascular risk factor, and gymnastics to increase
      strength, flexibility and coordination, as well as relaxation techniques are very
      effective exercises in a rehabilitation program. The positive influence of
      individual regular exercise on health, quality of life, physical exercise
      capacity, endurance, muscle strength, social, professional and emotional status
      is also very high in patients. Side effects of exercise are very rare.

PMID- 15966992
TI  - Vascular access for hemodialysis: arteriovenous fistula.
AB  - The long-term survival and quality of life of patients on hemodialysis (HD) is
      dependant on the adequacy of dialysis via an appropriately placed vascular
      access. The optimal vascular access is unquestionably the autologous
      arteriovenous fistula (AVF), with the most common method being the conventional
      radio-cephalic fistula at the wrist. Recent clinical practice guidelines
      recommend the creation of native fistula or synthetic graft before the start of
      chronic HD therapy to prevent the need for complication-prone dialysis catheters.
      This could also have a beneficial effect on the rapidity of worsening kidney
      failure. A multidisciplinary approach (nephrologists, surgeons, radiologists and
      nurses) should improve the HD outcome by promoting the use of AVF. An important
      additional component of this program is the Doppler ultrasound for preoperative
      vascular mapping. Such an approach may be realized without unsuccessful surgical
      explorations, with a minimal early failure rate and a high maturation, even in
      patients with diabetes mellitus.

PMID- 15966993
TI  - Hemodialysis catheters.
AB  - As a busy dialysis and apheresis unit and a referral center for vascular access,
      we had 850 hemodialysis catheter insertions in 2004, and >16 000 since 1976.
      According to data from literature and our experience, insertion should be guided
      by real-time ultrasonography whenever possible. Trisodium citrate in various
      concentrations (4-30%) seems to be a preferable locking solution (local
      anticoagulant and antimicrobial activity, no systemic anticoagulation, low
      price). Mupirocin at the exit site decreases the incidence of local infection and
      sepsis. The possible additive beneficial effects of the locking solution
      (citrate) and exit-site care with antibiotic (mupirocin, gentamycin) should be
      explored. According to our experience, temporary non-tunneled single-lumen
      catheters (one or two), with citrate locking and mupirocin at exit site, can be
      successfully used as a long-term vascular access in selected patients. The
      complications rate (malfunction and infection) of these catheters is comparable
      to tunneled, permanent catheters, but with the important advantage of easier
      insertion, exchange and removal.

PMID- 15966994
TI  - Convective dialysis therapies, current status and perspective.
AB  - When introduced in the 1970s, convective dialysis therapies were considered an
      attractive alternative to hemodialysis (HD), but technical and economical
      limitations prevented wide clinical application. Today, these therapies (i.e.
      hemofiltration and hemodiafiltration) are receiving renewed interest from the
      renal community. The main reason is the disappointment with current chronic
      dialysis therapy, which despite continuous integration of technical and
      pharmaceutical progress, has not provided significantly improved survival. The
      recent HEMO study showed that HD, even when administered at high dose and with
      high-flux membranes, has reached the limit of benefit for a representative
      dialysis population. At the same time there is new evidence supporting convective
      therapies. The extended range of solutes that is removed by convection as opposed
      to diffusion includes many molecules associated with uremic symptoms and
      complications. The hemodynamic stability characteristic of convective therapies
      is confirmed also in comparison with modern HD. Observational data indicates a
      survival benefit for patients treated with large volumes of convection.
      Continuously applied convective therapies are the preferred choice in severe
      cases of acute renal failure, and new membrane development may take these
      therapies to new applications of blood purification in the intensive care unit.

PMID- 15966995
TI  - Epoetin responsiveness in peritoneal dialysis patients: a multi-center Slovenian
      study.
AB  - The objective of our study was to assess the influence of residual renal function
      and other factors on epoetin requirements in chronic peritoneal dialysis
      patients. Fifty-one stable patients (mean age +/- SD: 52 +/- 13 years; 20 women)
      without recent bleeding, bone marrow disease or malignancy were recruited in four
      Slovenian centers. The target hemoglobin was above 110 g/L. The peritoneal
      equilibration test results and relevant clinical and laboratory parameters were
      recorded. The epoetin resistance index was expressed as a weekly epoetin
      dose/body weight/hemoglobin concentration. Twenty-four percent of the patients
      did not need epoetin treatment, the rest were treated with epoetin-beta in a dose
      of 70 +/- 56 U/kg per week s.c.; the hemoglobin concentration was 124 +/- 15 g/L.
      Ferritin >100 microg/L and transferrin saturation >20% fulfilled 63% of patients
      whose epoetin resistance index was not significantly lower (0.43 +/- 0.5 U/kg per
      week per g/L vs 0.6 +/- 0.72 U/kg per week per g/L, P = 0.502). No difference was
      found between diabetic and non-diabetic patients. Treatment with angiotensin
      system antagonists, but not with aluminum phosphate binders, was associated with
      increased epoetin resistance index (0.56 +/- 0.59 vs 0.3 +/- 0.4 U/kg per week
      per g/L, P = 0.038). No correlation between epoetin resistance index and residual
      glomerular filtration rate was found (r = -0.2, P = 0.173). A multiple linear
      regression analysis showed C-reactive protein, intact parathormone level, female
      sex and treatment with angiotensin system antagonists to be the independent
      predictors influencing epoetin resistance index. Our results show that systemic
      inflammation, secondary hyperparathyroidism and angiotensin system antagonist
      treatment are the most important modifiable parameters affecting epoetin
      requirements in stable peritoneal dialysis patients.

PMID- 15966996
TI  - Subcutaneous compared with intravenous epoetin treatment in patients on
      hemodialysis: one center study.
AB  - The use of epoetin has, in Europe, been restricted to the intravenous (i.v.)
      route in patients on hemodialysis. This study is aimed at investigating impacts
      of this change in policy. We retrospectively compared 45 hemodialysis patients
      treated with epoetin (alpha, beta) subcutaneously (subcutaneous [s.c.] period)
      for 12 months before and 12 months after changing the route from s.c. to i.v.,
      and 38 patients of the i.v. period who underwent long-term, i.v. low-dose iron
      therapy (i.v. iron period) for 6 months. During the study period, the dose of
      epoetin increased in the i.v. period compared to the s.c. period by 6.4% (7379 +/
      3556 IU/week [median 7846] vs 6907 +/- 3842 IU/week [median 5846], respectively
      [NS]). During the i.v. iron period, patients began to receive regular i.v. iron.
      The postiron epoetin dose was 5923 +/- 4779 IU/week (median 4500). The dose was
      decreased in comparison with the s.c. and i.v. periods by 14.2% and 19.7%,
      respectively. Hemoglobin decreased in the i.v. period compared to the s.c. period
      (120.4 +/- 8.0 g/L vs 123.5 +/- 6.7 g/L [P < 0.01]), and increased in the i.v.
      iron period compared to the s.c. and i.v. periods ([126.5 +/- 9.9 g/L vs 123.5 +/
      6.7 [P < 0.01]), and vs 120.4 +/- 8.0 (P < 0.01)]. Changing the route of
      administration of epoetin required an insignificant increase in dosage. Regular
      low-dose iron improves the response to epoetin and lowers the dose of epoetin,
      even in cases when the intravenously administration route is used.

PMID- 15966997
TI  - Citrate anticoagulation for single-needle hemodialysis: safety and efficacy.
AB  - Single-needle hemodialysis can be the only option in some patients and requires
      full heparinization. The aim of our retrospective clinical study was to evaluate
      the safety and efficacy of regional citrate anticoagulation for single-needle
      hemodialysis. Citrate anticoagulation was performed during 41 single-needle
      hemodialysis procedures in 24 patients at risk of bleeding, using 4% trisodium
      citrate, 1 M CaCl2 and calcium-free dialysate. Safety was assessed by the
      percentage of procedures that were terminated prematurely or changed to another
      modality due to citrate-related complications and by incidence of important
      hypocalcemia. Efficacy was evaluated by visually assessing clot formation in the
      circuit. Five per cent of the procedures were terminated prematurely. Important
      hypocalcemia was recorded in 34% of the procedures. Anticoagulation was
      suboptimal in 17% of the procedures, but none of the systems clotted. The median
      dialyzer assessment grade was excellent. The average protocol parameters were:
      blood flow 244 +/- 27 mL/min, starting rate of citrate 191 +/- 19 mL/h, starting
      rate of calcium 6.7 +/- 1.1 mL/h. In the first hour, ionized calcium decreased in
      67% of the procedures by 0.08 +/- 0.05 mmol/L. During the entire procedure,
      ionized calcium decreased in 80% of the cases by 0.17 +/- 0.09 mmol/L. There was
      a significant, but small increase in sodium (135 +/- 4 vs 137 +/- 4 mmol/L) and
      no increase in bicarbonate. Citrate anticoagulation during single-needle
      hemodialysis, according to our protocol, is safe and effective. Close monitoring
      of ionized calcium is mandatory. The calcium infusion rate should frequently be
      increased to correct hypocalcemia. The increased starting rate of calcium should
      be evaluated.

PMID- 15966998
TI  - Effects of handgrip training and intermittent compression of upper arm veins on
      forearm vessels in patients with end-stage renal failure.
AB  - The purpose of our study was to assess the influence of handgrip training and
      intermittent compression of the upper arm veins on forearm arteries and veins.
      Eighteen chronic hemodialysis patients performed daily handgrip training for 8
      weeks using a rubber ring, together with daily intermittent compression of the
      upper arm veins by elastic band. The forearm circumference, maximal handgrip
      strength, and arterial and vein parameters, including endothelium-dependent
      vasodilatation, were measured at the beginning, and after 4 and 8 weeks (using
      ultrasound scanning). The maximal handgrip strength and forearm circumference
      increased significantly. The radial artery diameters were significantly higher
      after 8 weeks of training (1.89 mm +/- 0.10 at the beginning, 1.95 +/- 0.10 mm
      after 8 weeks, P = 0.007), and endothelium-dependent vasodilatation was also
      found to be increased after 4 and 8 weeks of both activities. The venous
      parameters before tourniquet placement increased significantly after 8 weeks
      (2.40 +/- 0.16 mm at the beginning, 2.62 +/- 0.17 mm after 8 weeks, P = 0.014),
      and the venous parameters after tourniquet placement increased significantly
      after 4 and 8 weeks (3.36 +/- 0.17 mm at the beginning, 3.51 +/- 0.18 mm after 4
      weeks, P = 0.009), 3.68 +/- 0.18 mm after 8 weeks, P < 0.001). The distensibility
      of veins was preserved. Our results showed that handgrip training and
      intermittent compression of the upper arm veins, performed daily, increase the
      diameter of forearm arteries and veins and improve endothelium-dependent
      vasodilatation.

PMID- 15966999
TI  - Surgical salvage of thrombosed arteriovenous fistulas and grafts.
AB  - Our clinical experience with surgical salvage of thrombosed arteriovenous (AV)
      fistula and grafts, performed by a skilled interventional nephrologist is
      presented. A total of 286 surgical interventions were performed in 246 chronic
      hemodialysis patients aged 12-87 years (55 +/- 16 years), 268/286 (93.7%) in AV
      fistulas, 18/286 (6.3%) in grafts, and analyzed retrospectively. A subgroup of 61
      procedures was analyzed prospectively. The type of procedure, immediate success
      and patency after surgery were evaluated. Thrombectomy with reanastomosis was
      performed in 197/286 (68.9%) and simple thrombectomy in 89/286 (31.1%) of the
      procedures. The time from thrombosis to surgery was 1-60 days (3.7 +/- 1.8).
      Immediate success was achieved in 258/286 (90.2%) of surgical procedures, 95.5%
      (189/198) in thrombectomies with reanastomosis, and 77.5% (69/89) in simple
      thrombectomies. Primary and secondary patency rates for AV fistulas after
      surgical salvage at 3, 6, 9, and 12 months were 93.1, 84.0, 78.3, 75.0% and 96.6,
      88.0, 78.3, 77.3%, respectively. In order to maintain secondary patency, 1.15
      surgical procedures per AV fistula were needed. The time to thrombosis in grafts
      was on average 10.2 months, primary and secondary functioning time from
      thrombectomy (until the end of observation period) was from 1 to 19 months
      (average 6.9 +/- 6.3 months) and from 5.5 to 19 months (average 9.1 +/- 5.6
      months), respectively. In 7/16 (43.8%) surgical procedures, transluminal
      angioplasty and in 3/16 endovascular stent was placed after angioplasty. To
      maintain secondary patency, 2.3 surgical procedures per graft were needed. The
      surgical salvage of thrombosed AV fistulas and grafts, performed by a skilled
      interventional nephrologist, is successful in the short and long-term.

PMID- 15967001
TI  - Increased ethyl mercury load in protein a immunoadsorption.
AB  - Immunoadsorption is an adsorption technique for extracorporeal removal of
      circulating autoantibodies in autoimmune diseases. To prevent microbial growth
      during storage, the protein A columns are primed with thiomersal, which contains
      toxic ethyl mercury, which may be released during the procedure and potentially
      begin to accumulate and become toxic. To reduce the thiomersal-related mercury
      release during immunoadsorption treatment, we introduced a modified rinsing
      solution containing N-acetylcysteine, which is an avid mercury scavenger.
      Thirteen patients received 17 protein A immunoadsorption treatments and their
      venous blood samples were collected immediately before and after each session.
      The total blood mercury levels were measured by atomic absorption spectrometry,
      and the ethyl mercury levels by atomic fluorescence spectrometry. Following the
      manufacturer's recommendations, we used 600 mg of N-acetylcysteine to rinse the
      mercury from protein-loaded columns before each immunoadsorption treatment. After
      immunoadsorption, the ethyl mercury levels increased from 0.148 +/- 0.402 ng/g to
      2.026 +/- 1.944 ng/g (P < 0.001), and the total blood mercury levels increased
      from 2.447 +/- 3.065 ng/g to 20.437 +/- 28.603 ng/g (P = 0.02). The post
      treatment values of total blood mercury exceeded the upper safety level of 5 ng/g
      in all 17 immunoadsorption treatments, but no patient developed clinical signs of
      mercury toxicity. The results of our study showed an increase in total blood
      mercury and ethyl mercury levels during the immunoadsorption treatments,
      suggesting mercury release from thiomersal-primed columns despite the addition of
      N-acetylcysteine to the rinsing solution.

PMID- 15967000
TI  - Temporary hemodialysis catheters as a long-term vascular access in chronic
      hemodialysis patients.
AB  - The objective was to review our experience with temporary, precurved, jugular
      catheters used for long-term vascular access in chronic hemodialysis patients.
      Thirty chronic hemodialysis patients, 14 men and 16 women, with an average age of
      65.3 +/- 13.5 years (30-90 years), treated by dialysis for 1 month to 30 years
      (average +/- SD, 6.3 +/- 8.1 years), had single lumen, 'temporary' precurved non
      tunneled jugular catheters placed into the right jugular vein as permanent
      vascular access, with 4% trisodium citrate as a locking solution and mupirocin at
      the exit site. Hemodialysis catheters were used for vascular access on average
      for 9.1 +/- 6.5 months, (1-22.7 months), and for a total of 271.7 months (8151
      days). Average catheter functioning time was 3.1 +/- 1.9 months (0.5-10 months).
      The total number of side-effects was 55 (6.7/1000 catheter days), including 26
      cases of thrombosis (3.2/1000 catheter days), 9 ruptures of the catheter
      (1.1/1000 catheter days), 15 catheter malfunctions (1.8/1000 catheter days), 2
      exit site infections (0.2/1000 catheter days), 2 bacteremias (0.2/1000 catheter
      days), 1 avulsion of the catheter (0.1/1000 catheter days), and 2 catheters were
      removed because an AV fistula was successfully used. In 21 patients single-needle
      hemodialysis was performed, mean blood flow 251 +/- 16 mL/min (250-300), mean
      Kt/V 0.96 +/- 0.16 (0.72-1.27) and in 9 patients double-needle hemodialysis was
      performed (catheter and peripheral vein) with mean blood flow 252 +/- 14 mL/min
      (200-300), mean Kt/V 1.63 +/- 0.25 (1.21-1.96). 'Temporary' jugular single lumen
      non-tunneled hemodialysis catheters, with 4% citrate as locking solution and
      mupirocin ointment at the exit site provided good long-term vascular access with
      acceptable functioning time and low infection rate. The main reasons for catheter
      exchange or removal were malfunction and mechanical damage of the catheter.

PMID- 15967002
TI  - Citrate anticoagulation during plasma exchange in a patient with thrombotic
      thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate
      citrate load.
AB  - The treatment of thrombotic thrombocytopenic purpura requires plasma exchange
      using fresh frozen plasma as a replacement solution once or even twice daily. If
      citrate anticoagulation is needed, the citrate load (both from fresh frozen
      plasma and citrate as an anticoagulant) can be significant, causing metabolic
      complications. The aim of our report is to present our experience with citrate
      anticoagulation in a patient with thrombotic thrombocytopenic purpura treated
      with daily membrane plasma exchange. Twenty-six plasma exchange procedures were
      performed during 20 days of treatment in a 46-year-old female. The blood flow was
      98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/-
      11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen
      plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a
      replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of
      plasma was exchanged. No serious side-effects occurred. iCa before plasma
      exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/-
      0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges
      (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free
      hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and
      bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4
      mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six
      plasma exchanges. Citrate anticoagulation can be safely performed in patients
      treated with plasma exchange once or twice daily. Periodically performed short
      heparin-free hemodialysis can correct metabolic alkalosis and attenuate the
      citrate load.

PMID- 15967003
TI  - Prevention of early acute rejection with daclizumab and triple immunosuppression
      in cadaveric renal allograft recipients.
AB  - We carried out a prospective study of the safety and efficacy of daclizumab
      combined with triple immunosuppression in adult recipients of at least one HLA
      mismatched cadaveric renal allograft. All studied patients received the same
      immunosuppression: a daclizumab infusion of 1 mg/kg immediately before
      transplantation, and at 2, 4, 6, and 8 weeks following the transplantation.
      Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the
      operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on
      day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and
      mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to
      maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg
      per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients,
      with a mean age of 48 +/- 11 years, were studied. Six of them received a second
      renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time
      was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean
      latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft
      function. During a follow-up period of 3 months three acute rejection episodes
      occurred. One patient died because of systemic aspergillosis. After 3 months mean
      serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of
      them due to rejection. Patient and graft survival was 98.2% and 90.9%,
      respectively. Daclizumab with this triple therapy represents safe and efficient
      immunosuppression strategy, demonstrated with low incidence of early acute
      rejection episodes and an acceptable adverse event profile in cadaveric renal
      allograft recipients.

PMID- 15967004
TI  - Duplex-Doppler long-term follow-up of renal transplant artery stenosis: case
      controlled study.
AB  - The aim of this retrospective clinical study was to assess a long-term course of
      renal transplant artery stenosis with duplex-Doppler ultrasound, and its
      influence upon serum creatinine, hemoglobin concentration and hypertension, as
      well as to investigate a possible association between stenosis and the number of
      acute rejections. Thirty-four renal transplant recipients, aged 43 +/- 13 years,
      with significant (>50%) renal transplant artery stenosis as seen on Doppler
      ultrasound were compared with 34 renal transplant recipients without stenosis
      (excluded by Doppler). Patients of both groups were matched by age, sex, time of
      transplantation, type of renal transplant, and number of previous
      transplantations. We analyzed peak systolic velocity (PSV) in the renal
      transplant artery, resistance index (RI) at the level of intra-renal arteries,
      serum creatinine, hemoglobin concentration, blood pressure, the number of
      antihypertensive medications, and the number of acute rejections on a yearly
      basis. In the stenosis group, PSV was 2.1 +/- 0.5 m/s at 1 year after
      transplantation (controls 1.1 +/- 0.4), 1.9 +/- 0.5 at 2 years (0.9 +/- 0.4), 1.9
      +/- 0.5 at 3 years (0.9 +/- 0.4); RI was 62 +/- 10% at 1 year (controls 68 +/-
      7), 65 +/- 9 at 2 years (67 +/- 7), 63 +/- 9 at 3 years (67 +/- 7); serum
      creatinine was 128 +/- 58 micromol/L at 1 year (controls 129 +/- 43), 119 +/- 47
      at 2 years (121 +/- 33), 125 +/- 54 at 3 years (127 +/- 32). Long-term course of
      renal transplant artery stenosis (>50%), treated medically or interventionally,
      seems to be stable and non-progressive (during a 3-year follow up). Spontaneous
      regression of stenosis to non-significant level is possible. No difference in
      graft function, blood pressure or the number of acute rejections was observed
      comparing the stenotic and non-stenotic groups.

PMID- 15967005
TI  - Leukocytapheresis therapy modulates circulating t cell subsets in patients with
      ulcerative colitis.
AB  - The aim of this study was to elucidate the molecular mechanisms responsible for
      the therapeutic effects of leukocytapheresis (LCAP). We investigated the
      alterations in circulating T cell subsets after LCAP therapy in ulcerative
      colitis (UC) patients. Eighteen patients with UC were enrolled. Fourteen patients
      were responders, and four patients were non-responders. Peripheral venous blood
      was obtained within 5 min before and 5 min after LCAP therapy. Flow cytometric
      analysis for T cell markers and intracellular interferon (IFN)-gamma (Th1) and
      interleukin (IL)-4 (Th2) was then performed. The average numbers of lymphocytes,
      T and B cells were significantly decreased after LCAP therapy, respectively (P <
      0.01). The numbers of CD4+ and CD8+ T cells were also significantly decreased,
      respectively (P < 0.01), but the CD4+/CD8+ ratio was not changed. The number of
      CD45RO+ CD4+ memory T cells was significantly decreased. The number of CD25+ CD4+
      T cells tended to decrease after LCAP therapy (not significant). However, the
      ratio of CD25+ CD4+-cells/CD25- CD4+-cells was significantly increased (P <
      0.05). The number of IFN-gamma-positive (Th1) cells was significantly decreased
      after LCAP therapy, but there was no significant change in the number of IL-4
      positive (Th2) cells. The Th1/Th2 ratio was significantly decreased after LCAP
      therapy. Some of the immuno-suppressive effects of LCAP therapy may be associated
      with a modulation of circulating T cell subsets.

PMID- 15967008
TI  - UV-induced skin cancer: similarities--variations.
AB  - Skin cancer, the most common cancer world wide, encompasses different tumor
      entities, the keratinocyte-derived basal cell carcinoma (BCC), and squamous cell
      carcinoma (SCC) as well as the neuroectodermal malignant melanoma (MM) and the
      neuroendocrine Merkel cell carcinomas (MCC). While knowledge is significantly
      increasing about genetic changes contributing to BCCs and MMs, our understanding
      for the development and progression of SCCs and MCCs is still fragmentary. This
      review, thus, aims, on the one hand to summarize the present knowledge without
      claiming completeness and, on the other hand, to provide information on the HaCaT
      in vitro skin carcinogenesis model that is used to evaluate the functional
      consequence of genetic aberrations believed to play a role in skin cancer
      development and progression.

PMID- 15967006
TI  - Emollients with endocannabinoids in the treatment of uremic pruritus: discussion
      of the therapeutic options.

PMID- 15967009
TI  - [UV-induced regulatory T cells].
AB  - Regulatory T cells belong to a subset of T lymphocytes which suppress immune
      reactions in an antigen-specific fashion. Regulatory T cells play an important
      role in the prevention of autoimmune diseases. Ultraviolet (UV) radiation
      suppresses the immune system in antigen-specific fashion. This effect is mediated
      by UV-induced regulatory T cells. UV-induced regulatory T cells express CD4 and
      CD25 and upon activation release the immunosuppressive cytokine interleukin-10.
      Upon intravenous injection UV-induced regulatory T cells primarily migrate into
      the lymph nodes, explaining why they preferentially suppress sensitization.
      Recently, the development of regulatory T cells was demonstrated in an
      experimental model of photopheresis. The further characterisation of these cells
      will determine whether they can be applied in the future therapeutically with the
      ultimate aim to induce specific immunosuppression.

PMID- 15967010
TI  - Cost-of-illness in patients with moderate and severe chronic psoriasis vulgaris
      in Germany.
AB  - BACKGROUND: Data regarding costs of outpatient and office-based care, as well as
      out-of-pocket expenses, for psoriasis patients in Germany are not available. Aim
      of this study was to assess average annual cost and cost per flare of outpatient
      and office-based care for patients with moderate to severe chronic psoriasis
      vulgaris from several perspectives. METHODS: In this multi-center, cross
      sectional, retrospective and prospective cost-of-illness study, direct (medical
      and non-medical) and indirect costs were considered from patient, third-party
      payer (TPP) and societal perspectives. RESULTS: Out of 227 patients enrolled
      consecutively in 17 centers, 192 cases could be analyzed. On average, TPP
      reimbursed 864 per patient annually, 60 % for prescribed medication and 22 % for
      hospitalization. Patients spent 596 yearly mainly for alternative therapies and
      OTC-medication/skin care products as well as for additional expenses (e. g.
      ultraviolet lamp, clothes or cleaning agents). Indirect costs per patient
      amounted to 1,440 yearly. Total annual costs per patient were 2,866 and 4,985 if
      treated with systemic drugs additionally. 1,173 if treated topically and/or with
      phototherapy. CONCLUSIONS: The relatively high average annual costs per patient
      indicate need for efficient control of psoriasis. This cost-of-illness study
      provides basic data for further decision making, including economic assessment of
      innovative therapies for psoriasis.

PMID- 15967011
TI  - [Maintenance treatment and early intervention--the new paradigm in the management
      of atopic eczema].

PMID- 15967012
TI  - [Excimer laser therapy of alopecia areata--side-by-side evaluation of a
      representative area].
AB  - We report for the first time on hair regrowth in alopecia areata of the scalp
      achieved with the 308-nm xenon-chloride excimer laser in a prospective side-by
      side trial. The alopecia areata had shown progression over a period of three
      years, and various treatments had not been effective. Out of a number of affected
      areas, one representative lesion was chosen; one half of it was treated, the
      other half remained untreated. After 27 sessions (200 - 4000 mJ/cm2, cumulative
      dose 52.6 J/cm2) over 3 months, only the treated area showed hair growth; which
      suggests that this was most probably not a spontaneous remission.

PMID- 15967013
TI  - [Contact dermatitis to permanent make up: manifestation of a pre-existing nickel
      allergy].
AB  - During recent years demands for permanent make up and especially permanent lip
      liner is increasing not only in the USA but also in Germany. Adverse reactions to
      these products are almost unknown and not documented in literature. Declaration
      of contents and side effects are not required for tattoo colors, in contrast to
      the rules for medical treatments. Our patient developed inflammation and
      vesiculation within the area of tattooing three days after injection of a
      permanent lip liner. Treatment with steroids induced complete resolution of the
      lip liner-associated dermatitis. However, not only the effect of the lip liner
      was lost but also the natural color of her lip was partly destroyed by
      inflammation. Diagnostic allergy testing revealed strong delayed hypersensitivity
      to nickel and a mild patch test reaction to the permanent lip liner. Examination
      of the permanent make-up by mass spectrometry detected nickel in a concentration
      of 1.8 ppm. No allergic reaction could be seen when the purified red dye itself
      was tested. This patient with pre-existing nickel allergy developed an allergic
      contact dermatitis from the injection of a permanent lip liner contaminated with
      nickel.

PMID- 15967014
TI  - Eosinophilic cellulitis (Wells' syndrome) associated with colon carcinoma.
AB  - Eosinophilic cellulitis (Wells' syndrome) is an inflammatory dermatosis
      characterized by marked eosinophilic infiltrates. Drugs and various infections
      are recognized causes of eosinophilic cellulitis. Eosinophilic cellulitis has
      been reported in non-hematological malignancies in two patients with squamous
      cell carcinoma and one with nasopharyngeal carcinoma. We report the association
      of eosinophilic cellulitis with adenocarcinoma of the colon. Curative
      hemicolectomy led to a complete remission, suggesting that underlying
      malignancies can trigger eosinophilic cellulitis.

PMID- 15967015
TI  - [Andrological relevance of testicular biopsies].

PMID- 15967016
TI  - [A "yellow" girl. Hypercarotenaemia in anorexia nervosa].

PMID- 15967017
TI  - [Guideline--gynecomastia].

PMID- 15967018
TI  - [Legal aspects of teledermatology].
AB  - Teledermatology places special demanding on participating physicians who are not
      only required to exercise the normal standard of care in diagnosis and treatment,
      but must also have additional obligations. The teledermatologist must have
      sufficient technical background to recognize if and how information transmitted
      by electronic media can serve as a basis for reliable diagnosis. He must work
      with an information transfer system which meets technical standards and legal
      requirments. Patient data security and data privacy requires special attention,
      as does the competence and legal status of the referring physician worker.

PMID- 15967019
TI  - EMPACT syndrome.

PMID- 15967021
TI  - Golf and upper limb injuries: a summary and review of the literature.
AB  - BACKGROUND: Golf is a popular past time that provides exercise with social
      interaction. However, as with all sports and activities, injury may occur. Many
      golf-related injuries occur in the upper limb, yet little research on the
      potential mechanisms of these injuries has been conducted. OBJECTIVE: To review
      the current literature on golf-related upper limb injuries and report on
      potential causes of injury as it relates to the golf swing. DISCUSSION: An
      overview of the golf swing is described in terms of its potential to cause the
      frequently noted injuries. Most injuries occur at impact when the golf club hits
      the ball. This paper concludes that more research into golf-related upper limb
      injuries is required to develop a thorough understanding of how injuries occur.
      Types of research include epidemiology studies, kinematic swing analysis and
      electromyographic studies of the upper limb during golf. By conducting such
      research, preventative measures maybe developed to reduce golf related injury.

PMID- 15967022
TI  - Iterative approach to model identification of biological networks.
AB  - BACKGROUND: Recent advances in molecular biology techniques provide an
      opportunity for developing detailed mathematical models of biological processes.
      An iterative scheme is introduced for model identification using available system
      knowledge and experimental measurements. RESULTS: The scheme includes a state
      regulator algorithm that provides estimates of all system unknowns
      (concentrations of the system components and the reaction rates of their inter
      conversion). The full system information is used for estimation of the model
      parameters. An optimal experiment design using the parameter identifiability and
      D-optimality criteria is formulated to provide "rich" experimental data for
      maximizing the accuracy of the parameter estimates in subsequent iterations. The
      importance of model identifiability tests for optimal measurement selection is
      also considered. The iterative scheme is tested on a model for the caspase
      function in apoptosis where it is demonstrated that model accuracy improves with
      each iteration. Optimal experiment design was determined to be critical for model
      identification. CONCLUSION: The proposed algorithm has general application to
      modeling a wide range of cellular processes, which include gene regulation
      networks, signal transduction and metabolic networks.

PMID- 15967023
TI  - FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble
      a lung primary: a diagnostic pitfall.
AB  - BACKGROUND: As extra-cranial metastasis of glioblastoma multiforme (GBM) is rare,
      it may create a diagnostic dilemma especially during interpretation of fine
      needle aspiration biopsy (FNAB) cytology. CASE PRESENTATION: We present
      transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically
      suspicious for a lung primary. The smears of transbronchial FNAB showed groups of
      cells with ill-defined cell margins and cytological features overlapping with
      poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack
      of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual
      neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed
      cellblock sections. However, they were immunoreactive for the other
      neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further
      scrutiny of clinical details revealed a history of GBM, 13 months status-post
      surgical excision with radiation therapy and systemic chemotherapy. The tumor
      recurred 7 months earlier and was debulked surgically and with intra-cranial
      chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic
      protein (GFAP) immunoreactivity with clinical details resulted in final
      interpretation of metastatic GBM. CONCLUSION: Lack of clinical history and
      immunophenotyping may lead to a diagnostic pitfall with possible
      misinterpretation of metastatic GBM as poorly differentiated non-small cell
      carcinoma of lung in a smoker.

PMID- 15967024
TI  - Effective ambiguity checking in biosequence analysis.
AB  - BACKGROUND: Ambiguity is a problem in biosequence analysis that arises in various
      analysis tasks solved via dynamic programming, and in particular, in the modeling
      of families of RNA secondary structures with stochastic context free grammars.
      Several types of analysis are invalidated by the presence of ambiguity. As this
      problem inherits undecidability (as we show here) from the namely problem for
      context free languages, there is no complete algorithmic solution to the problem
      of ambiguity checking. RESULTS: We explain frequently observed sources of
      ambiguity, and show how to avoid them. We suggest four testing procedures that
      may help to detect ambiguity when present, including a just-in-time test that
      permits to work safely with a potentially ambiguous grammar. We introduce, for
      the special case of stochastic context free grammars and RNA structure modeling,
      an automated partial procedure for proving non-ambiguity. It is used to
      demonstrate non-ambiguity for several relevant grammars. CONCLUSION: Our
      mechanical proof procedure and our testing methods provide a powerful arsenal of
      methods to ensure non-ambiguity.

PMID- 15967025
TI  - Inbred mouse strains C57BL/6J and DBA/2J vary in sensitivity to a subset of
      bitter stimuli.
AB  - BACKGROUND: Common inbred mouse strains are genotypically diverse, but it is
      still poorly understood how this diversity relates to specific differences in
      behavior. To identify quantitative trait genes that influence taste behavior
      differences, it is critical to utilize assays that exclusively measure the
      contribution of orosensory cues. With a few exceptions, previous
      characterizations of behavioral taste sensitivity in inbred mouse strains have
      generally measured consumption, which can be confounded by post-ingestive
      effects. Here, we used a taste-salient brief-access procedure to measure taste
      sensitivity to eight stimuli characterized as bitter or aversive in C57BL/6J (B6)
      and DBA/2J (D2) mice. RESULTS: B6 mice were more sensitive than D2 mice to a
      subset of bitter stimuli, including quinine hydrochloride (QHCl), 6-n
      propylthiouracil (PROP), and MgCl2. D2 mice were more sensitive than B6 mice to
      the bitter stimulus raffinose undecaacetate (RUA). These strains did not differ
      in sensitivity to cycloheximide (CYX), denatonium benzoate (DB), KCl or HCl.
      CONCLUSION: B6-D2 taste sensitivity differences indicate that differences in
      consumption of QHCl, PROP, MgCl2 and RUA are based on immediate orosensory cues,
      not post-ingestive effects. The absence of a strain difference for CYX suggests
      that polymorphisms in a T2R-type taste receptor shown to be differentially
      sensitive to CYX in vitro are unlikely to differentially contribute to the CYX
      behavioral response in vivo. The results of these studies point to the utility of
      these common mouse strains and their associated resources for investigation into
      the genetic mechanisms of taste.

PMID- 15967028
TI  - Giant viruses in the oceans: the 4th Algal Virus Workshop.
AB  - Giant double-stranded DNA viruses (such as record breaking Acanthamoeba polyphaga
      Mimivirus), with particle sizes of 0.2 to 0.6 microm, genomes of 300 kbp to 1.200
      kbp, and commensurate complex gene contents, constitute an evolutionary mystery.
      They challenge the common vision of viruses, traditionally seen as highly
      streamlined genomes optimally fitted to the smallest possible--filterable-
      package. Such giant viruses are now discovered in increasing numbers through the
      systematic sampling of ocean waters as well as freshwater aquatic environments,
      where they play a significant role in controlling phyto- and bacterio- plankton
      populations. The 4th Algal Virus Workshop showed that the study of these
      ecologically important viruses is now massively entering the genomic era,
      promising a better understanding of their diversity and, hopefully, some insights
      on their origin and the evolutionary forces that shaped their genomes.

PMID- 15967026
TI  - ATP-binding cassette (ABC) transporters in normal and pathological lung.
AB  - ATP-binding cassette (ABC) transporters are a family of transmembrane proteins
      that can transport a wide variety of substrates across biological membranes in an
      energy-dependent manner. Many ABC transporters such as P-glycoprotein (P-gp),
      multidrug resistance-associated protein 1 (MRP1) and breast cancer resistance
      protein (BCRP) are highly expressed in bronchial epithelium. This review aims to
      give new insights in the possible functions of ABC molecules in the lung in view
      of their expression in different cell types. Furthermore, their role in
      protection against noxious compounds, e.g. air pollutants and cigarette smoke
      components, will be discussed as well as the (mal)function in normal and
      pathological lung. Several pulmonary drugs are substrates for ABC transporters
      and therefore, the delivery of these drugs to the site of action may be highly
      dependent on the presence and activity of many ABC transporters in several cell
      types. Three ABC transporters are known to play an important role in lung
      functioning. Mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene can cause cystic fibrosis, and mutations in ABCA1 and ABCA3 are
      responsible for respectively Tangier disease and fatal surfactant deficiency. The
      role of altered function of ABC transporters in highly prevalent pulmonary
      diseases such as asthma or chronic obstructive pulmonary disease (COPD) have
      hardly been investigated so far. We especially focused on polymorphisms, knock
      out mice models and in vitro results of pulmonary research. Insight in the
      function of ABC transporters in the lung may open new ways to facilitate
      treatment of lung diseases.

PMID- 15967027
TI  - Viral promoters can initiate expression of toxin genes introduced into
      Escherichia coli.
AB  - BACKGROUND: The expression of recombinant proteins in eukaryotic cells requires
      the fusion of the coding region to a promoter functional in the eukaryotic cell
      line. Viral promoters are very often used for this purpose. The preceding cloning
      procedures are usually performed in Escherichia coli and it is therefore of
      interest if the foreign promoter results in an expression of the gene in
      bacteria. In the case molecules toxic for humans are to be expressed, this
      knowledge is indispensable for the specification of safety measures. RESULTS: We
      selected five frequently used viral promoters and quantified their activity in E.
      coli with a reporter system. Only the promoter from the thymidine kinase gene
      from HSV1 showed no activity, while the polyhedrin promoter from baculovirus, the
      early immediate CMV promoter, the early SV40 promoter and the 5' LTR promoter
      from HIV-1 directed gene expression in E. coli. The determination of
      transcription start sites in the immediate early CMV promoter and the polyhedrin
      promoter confirmed the existence of bacterial -10 and -35 consensus sequences.
      The importance of this heterologous gene expression for safety considerations was
      further supported by analysing fusions between the aforementioned promoters and a
      promoter-less cytotoxin gene. CONCLUSION: According to our results a high
      percentage of viral promoters have the ability of initiating gene expression in
      E. coli. The degree of such heterologous gene expression can be sufficient for
      the expression of toxin genes and must therefore be considered when defining
      safety measures for the handling of corresponding genetically modified organisms.

PMID- 15967029
TI  - The ups and downs of biological timers.
AB  - BACKGROUND: The need to execute a sequence of events in an orderly and timely
      manner is central to many biological processes, including cell cycle progression
      and cell differentiation. For self-perpetuating systems, such as the cell cycle
      oscillator, delay times between events are defined by the network of interacting
      proteins that propagates the system. However, protein levels inside cells are
      subject to genetic and environmental fluctuations, raising the question of how
      reliable timing is maintained. RESULTS: We compared the robustness of different
      mechanisms for encoding delay times to fluctuations in protein expression levels.
      Gradual accumulation and gradual decay of a regulatory protein have an equivalent
      capacity for defining delay times. Yet, we find that the former is highly
      sensitive to fluctuations in gene dosage, while the latter can buffer such
      perturbations. In particular, a positive feedback where the degrading protein
      auto-enhances its own degradation may render delay times practically insensitive
      to gene dosage. CONCLUSION: While our understanding of biological timing
      mechanisms is still rudimentary, it is clear that there is an ample use of
      degradation as well as self-enhanced degradation in processes such as cell cycle
      and circadian clocks. We propose that degradation processes, and specifically
      self-enhanced degradation, will be preferred in processes where maintaining the
      robustness of timing is important.

PMID- 15967030
TI  - Washing our hands of the congenital cytomegalovirus disease epidemic.
AB  - BACKGROUND: Each year in the United States, an estimated 40,000 children are born
      with congenital cytomegalovirus (CMV) infection, causing an estimated 400 deaths
      and leaving approximately 8000 children with permanent disabilities such as
      hearing or vision loss, or mental retardation. More children are affected by
      serious CMV-related disabilities than by several better-known childhood maladies,
      including Down syndrome, fetal alcohol syndrome, and spina bifida. DISCUSSION:
      Congenital CMV is a prime target for prevention not only because of its
      substantial disease burden but also because the biology and epidemiology of CMV
      suggest that there are ways to reduce viral transmission. Because exposure to the
      saliva or urine of young children is a major cause of CMV infection among
      pregnant women, it is likely that good personal hygiene, especially hand-washing,
      can reduce the risk of CMV acquisition. Experts agree that such measures are
      likely to be efficacious (i.e., they will work if consistently followed) and the
      American College of Obstetricians and Gynecologists recommends that physicians
      counsel pregnant women about preventing CMV acquisition through careful attention
      to hygiene. However, because of concerns about effectiveness (i.e., Will women
      consistently follow hygienic practices as the result of interventions?), the
      medical and public health communities appear reluctant to embrace primary CMV
      prevention via improved hygienic practices, and educational interventions are
      rare. Current data on the effectiveness of such measures in preventing CMV
      infection are promising, but limited. There is strong evidence, however, that
      educational interventions can prevent other infectious diseases with similar
      transmission modes, suggesting that effective interventions can also be found for
      CMV. Until a CMV vaccine becomes available, effective educational interventions
      are needed to inform women about congenital CMV prevention. SUMMARY: Perhaps no
      single cause of birth defects and developmental disabilities in the United States
      currently provides greater opportunity for improved outcomes in more children
      than congenital CMV. Given the present state of knowledge, women deserve to be
      informed about how they can reduce their risk of CMV infection during pregnancy,
      and trials are needed to identify effective educational interventions.

PMID- 15967031
TI  - Tools enabling the elucidation of molecular pathways active in human disease:
      application to Hepatitis C virus infection.
AB  - BACKGROUND: The extraction of biological knowledge from genome-scale data sets
      requires its analysis in the context of additional biological information. The
      importance of integrating experimental data sets with molecular interaction
      networks has been recognized and applied to the study of model organisms, but its
      systematic application to the study of human disease has lagged behind due to the
      lack of tools for performing such integration. RESULTS: We have developed
      techniques and software tools for simplifying and streamlining the process of
      integration of diverse experimental data types in molecular networks, as well as
      for the analysis of these networks. We applied these techniques to extract, from
      genomic expression data from Hepatitis C virus-infected liver tissue, potentially
      useful hypotheses related to the onset of this disease. Our integration of the
      expression data with large-scale molecular interaction networks and subsequent
      analyses identified molecular pathways that appear to be induced or repressed in
      the response to Hepatitis C viral infection. CONCLUSION: The methods and tools we
      have implemented allow for the efficient dynamic integration and analysis of
      diverse data in a major human disease system. This integrated data set in turn
      enabled simple analyses to yield hypotheses related to the response to Hepatitis
      C viral infection.

PMID- 15967032
TI  - Lack of evidence for a genetic association between FGF20 and Parkinson's disease
      in Finnish and Greek patients.
AB  - BACKGROUND: Fibroblast growth factor 20 (FGF20) is a neurotrophic factor
      preferentially expressed in the substantia nigra of rat brain and could be
      involved in dopaminergic neurons survival. Recently, a strong genetic association
      has been found between FGF20 gene and the risk of suffering from Parkinson's
      disease (PD). Our aim was to replicate this association in two independent
      populations. METHODS: Allelic, genotypic, and haplotype frequencies of four
      biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls
      from Greece, and 144 sporadic PD patients and 135 controls from Finland. RESULTS:
      No association was found in any of the populations studied. CONCLUSION: Taken
      together, these findings suggest that common genetic variants in FGF20 are not a
      risk factor for PD in, at least, some European populations.

PMID- 15967033
TI  - Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco
      regional recurrence after preoperative radiotherapy in rectal cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) represents a major target for
      current radiosensitizing strategies. We wished to ascertain whether a correlation
      exists between the expression of EGFR and treatment outcome in a group of
      patients with rectal adenocarcinoma who had undergone preoperative radiotherapy
      (RT). METHODS: Within a six-year period, 138 patients underwent preoperative
      radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our
      institute. Among them, 77 pretherapeutic tumor biopsies were available for semi
      quantitative immunohistochemical investigation evaluating the intensity and the
      number (extent) of tumor stained cells. Statistical analyses included Cox
      regression for calculating risk ratios of survival endpoints and logistic
      regression for determining odds ratios for the development of loco-regional
      recurrences. RESULTS: Median age was 64 years (range: 30-88). Initial staging
      showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy
      pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal
      cancer patients the primary tumor received a boost dose of up to 16 Gy for a
      sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the
      cases. All patients underwent complete total mesorectal resection. Positive
      staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36
      months (range: 6-86). Locoregional recurrence rates were 7 and 20% for EGFR
      extent inferior and superior to 25%, respectively. The corresponding locoregional
      recurrence-free survival rate at two years was 94% (95% confidence interval, CI,
      92-98%) and 84% (CI 95%, 58-95%), respectively (P = 0.06). Multivariate analyses
      showed a significant correlation between the rate of loco-regional recurrence and
      three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17
      46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92,
      CI 95%, 1.18-40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78,
      CI 95%, 1.04-32.05, P = 0.045). CONCLUSION: EGFR expression impacts on loco
      regional recurrence. Knowledge of expression of EGFR in rectal cancer could
      contribute to the identification of patients with an increased risk of
      recurrences, and to the prediction of prognosis.

PMID- 15967034
TI  - Online clinical reasoning assessment with the Script Concordance test: a
      feasibility study.
AB  - BACKGROUND: The script concordance (SC) test is an assessment tool that measures
      capacity to solve ill-defined problems, that is, reasoning in context of
      uncertainty. This tool has been used up to now mainly in medicine. The purpose of
      this pilot study is to assess the feasibility of the test delivered on the Web to
      French urologists. METHODS: The principle of SC test construction and the
      development of the Web site are described. A secure Web site was created with two
      sequential modules: (a) The first one for the reference panel (n = 26) with two
      sub-tasks: to validate the content of the test and to elaborate the scoring
      system; (b) The second for candidates with different levels of experience in
      Urology: Board certified urologists, residents, medical students (5 or 6th year).
      Minimum expected number of participants is 150 for urologists, 100 for residents
      and 50 for medical students. Each candidate is provided with an individual access
      code to this Web site. He/she may complete the Script Concordance test several
      times during his/her curriculum. RESULTS: The Web site has been operational since
      April 2004. The reference panel validated the test in June of the same year
      during the annual seminar of the French Society of Urology. The Web site is
      available for the candidates since September 2004. In six months, 80% of the
      target figure for the urologists, 68% of the target figure for the residents and
      20% of the target figure for the student passed the test online. During these six
      months, no technical problem was encountered. CONCLUSION: The feasibility of the
      web-based SC test is successful as two-thirds of the expected number of
      participants was included within six months. Psychometric properties (validity,
      reliability) of the test will be evaluated on a large scale (N = 300). If
      positive, educational impact of this assessment tool will be useful to help
      urologists during their curriculum for the acquisition of clinical reasoning
      skills, which is crucial for professional competence.

PMID- 15967035
TI  - Interleukin 1 receptor antagonist knockout mice show enhanced microglial
      activation and neuronal damage induced by intracerebroventricular infusion of
      human beta-amyloid.
AB  - BACKGROUND: Interleukin 1 (IL-1) is a key mediator of immune responses in health
      and disease. Although classically the function of IL-1 has been studied in the
      systemic immune system, research in the past decade has revealed analogous roles
      in the CNS where the cytokine can contribute to the neuroinflammation and
      neuropathology seen in a number of neurodegenerative diseases. In Alzheimer's
      disease (AD), for example, pre-clinical and clinical studies have implicated IL-1
      in the progression of a pathologic, glia-mediated pro-inflammatory state in the
      CNS. The glia-driven neuroinflammation can lead to neuronal damage, which, in
      turn, stimulates further glia activation, potentially propagating a detrimental
      cycle that contributes to progression of pathology. A prediction of this
      neuroinflammation hypothesis is that increased IL-1 signaling in vivo would
      correlate with increased severity of AD-relevant neuroinflammation and neuronal
      damage. METHODS: To test the hypothesis that increased IL-1 signaling predisposes
      animals to beta-amyloid (Abeta)-induced damage, we used IL-1 receptor antagonist
      Knock-Out (IL1raKO) and wild-type (WT) littermate mice in a model that involves
      intracerebroventricular infusion of human oligomeric Abeta1-42. This model mimics
      many features of AD, including robust neuroinflammation, Abeta plaques, synaptic
      damage and neuronal loss in the hippocampus. IL1raKO and WT mice were infused
      with Abeta for 28 days, sacrificed at 42 days, and hippocampal endpoints
      analyzed. RESULTS: IL1raKO mice showed increased vulnerability to Abeta-induced
      neuropathology relative to their WT counterparts. Specifically, IL1raKO mice
      exhibited increased mortality, enhanced microglial activation and
      neuroinflammation, and more pronounced loss of synaptic markers. Interestingly,
      Abeta-induced astrocyte responses were not significantly different between WT and
      IL1raKO mice, suggesting that enhanced IL-1 signaling predominately affects
      microglia. CONCLUSION: Our data are consistent with the neuroinflammation
      hypothesis whereby increased IL-1 signaling in AD enhances glia activation and
      leads to an augmented neuroinflammatory process that increases the severity of
      neuropathologic sequelae.

PMID- 15967036
TI  - Influence of photoperiod and running wheel access on the entrainment of split
      circadian rhythms in hamsters.
AB  - BACKGROUND: In the laboratory, behavioral and physiological states of nocturnal
      rodents alternate, with a period near 24 h, between those appropriate for the
      night (e.g., elevated wheel-running activity and high melatonin secretion) and
      for the day (e.g., rest and low melatonin secretion). Under appropriate 24 h
      light:dark:light:dark conditions, however, rodents may be readily induced to
      express bimodal rest/activity cycles that reflect a global temporal
      reorganization of the central neural pacemaker in the hypothalamus. We examine
      here how the relative length of the light and dark phases of the environmental
      cycle influences this rhythm splitting and the necessity of a running wheel for
      expression of this entrainment condition. RESULTS: Rhythm splitting was observed
      in wheel-running and general locomotion of Siberian and Syrian hamsters. The
      latter also manifest split rhythms in body temperature. Access to a running wheel
      was necessary neither for the induction nor maintenance of this entrainment
      pattern. While rhythms were only transiently split in many animals with two 5 h
      nights, the incidence of splitting was greater with twice daily nights of shorter
      duration. Removal of running wheels altered the body temperature rhythm but did
      not eliminate its clear bimodality. CONCLUSION: The expression of entrained,
      split circadian rhythms exhibits no strict dependence on access to a running
      wheel, but can be facilitated by manipulation of ambient lighting conditions.
      These circadian entrainment patterns may be of therapeutic value to human shift
      workers and others facing chronobiological challenges.

PMID- 15967037
TI  - TRIM5alpha selectively binds a restriction-sensitive retroviral capsid.
AB  - TRIM5 is a potent retrovirus inhibitor that targets viruses bearing particular
      capsid (CA) residues. In most primate species, retroviral restriction requires
      the C-terminal SPRY domain unique to the alpha-isoform of TRIM5, but the
      mechanism by which susceptible viruses are recognized and targeted for
      restriction is unknown. Here we show that TRIM5alpha binds retroviral CA from
      detergent-stripped virions in a SPRY-dependent manner with sufficient
      discrimination to account for the exquisite specificity of restriction.

PMID- 15967038
TI  - Goblet cell carcinoid of the appendix.
AB  - BACKGROUND: Goblet cell carcinoid (GCC) of the appendix is a rare neoplasm that
      share histological features of both adenocarcinoma and carcinoid tumor. While its
      malignant potential remains unclear, GCC's are more aggressive than conventional
      carcinoid. The clinical presentations of this neoplasm are also varied. This
      review summarizes the published literature on GCC of the appendix. The focus is
      on its diagnosis, histopathological aspects, clinical manifestations, and
      management. METHODS: Published studies in the English language between 1966 to
      2004 were identified through Medline keyword search utilizing terms "goblet cell
      carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of
      the appendix. RESULTS: Based on the review of 57 published papers encompassing
      nearly 600 diagnosed patients, the mean age of presentation for GCC of the
      appendix was 58.89 years with equal representation in both males and females.
      Accurate diagnosis of this neoplasm requires astute observations within an
      acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal
      growth and usually lacks the formation of a well-defined tumor mass. The
      mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%.
      The most common clinical presentations in order of frequency were acute
      appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in
      5.15% and an appendicular mass in 3.09%. The most common surgical treatment of
      choice was appendectomy with right hemicolectomy in 34.70% followed by simple
      appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present
      in 11.16% of patients with the ovaries being the most common site in 3.60%
      followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node
      involvement was seen in 8.76% of patients at the time of diagnosis. The reported
      5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm
      of unpredictable biological behavior and thus warrants lifelong surveillance for
      recurrence of the disease upon diagnosis and successful surgical extirpation.
      CONCLUSION: GCC of the appendix is a rare neoplasm. Due to its wide range of
      presentation, this tumor should be considered as a possible diagnosis in many
      varied situations leading to abdominal surgery. Histopathological features such
      as increased number of Paneth cells, increased amount of mucin secretion and
      presence of pancreatic polypeptide may predict a more aggressive behavior. The
      advocated plan of management recommended for patients with tumors that involve
      the adjacent caecum or with high-grade tumors with histological features such as
      an increased mitotic rate involve initial appendectomy with completion right
      hemicolectomy due to the high possibility of local recurrence with
      intraperitoneal seeding prior to lymph node involvement and a 20% risk of
      metastatic behavior. In female patients with GCC of the appendix regardless of
      age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread
      of the disease chemotherapy, mostly with 5-FU and leucovorin is advised.
      Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer
      improved survival in cases with advanced peritoneal dissemination.

PMID- 15967039
TI  - The level of recognition of physical symptoms in patients with a major depression
      episode in the outpatient psychiatric practice in Puerto Rico: an observational
      study.
AB  - BACKGROUND: This study was designed to evaluate the psychiatrists' level of
      recognition of somatic symptoms associated to a major depressive episode (MDE)
      (DSM-IV-TR criteria) and the impact of those somatic symptoms on the treatment
      effectiveness. METHODS: This non-interventional study was conducted in 25 medical
      offices in Puerto Rico from February to December 2003. It had 2 visits separated
      by 8 weeks. The level of recognition was determined by: the correlation between
      the physician clinical evaluation and their patients' self-evaluations through
      different validated instruments using kappa statistics. Chi-square test was used
      to evaluate the impact of somatic symptoms on treatment antidepressants'
      effectiveness. RESULTS: All the 145 recruited patients reported the presence of
      at least one somatic symptom associated with their current MDE. In the two visits
      covered by the study, a fair agreement between the psychiatrists' and the
      patients' reports was noted for headache, abdominal pain and upper limb pains
      (0.4003 <or= kappa >or= 0.6594). For other painful symptoms and painless somatic
      symptoms, the Kappa values obtained were non-significant. Slight but significant
      reductions in depression and painful symptoms severity were observed after 8
      weeks of treatment. A proportional relationship between the pain and depression
      severity was observed (p < 0.0001). CONCLUSION: The study results show that
      somatic symptoms: are very common in depressed Puerto Rican patients; are
      significant under-reported by psychiatrists; and have a significant impact on the
      antidepressant effectiveness.

PMID- 15967041
TI  - Annular pigment band on the posterior capsule following blunt ocular trauma: a
      case report.
AB  - BACKGROUND: To report an unusual case of annular pigment band on the posterior
      capsule following blunt ocular trauma. CASE PRESENTATION: We describe an annular
      pigment band on the posterior capsule following blunt ocular trauma in a 28-year
      old male patient. Repeat examinations revealed no evidence of other signs of
      blunt ocular trauma or pigment dispersion syndrome in either eye. CONCLUSION: The
      annular pigment band in this case corresponds to the adherence of the
      hyaloideocapsulare ligament to the posterior capsule and reconfirms its rare
      visualization in the living eye. This finding may be an isolated sign of blunt
      ocular trauma and a compromised integrity of the vitreolenticular interface
      should be strongly suspected. We recommend careful documentation in context of
      future cataract surgery in these eyes.

PMID- 15967040
TI  - A Severe Acute Respiratory Syndrome Extranet: supporting local communication and
      information dissemination.
AB  - BACKGROUND: The objective of this study was to explore the use and perceptions of
      a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to
      support future information and communication applications. The SARS Extranet was
      a single, managed electronic and limited access system to manage local,
      provincial and other SARS control information. METHODS: During July, 2003, a web
      based and paper-based survey was conducted with 53 SARS Steering Committee
      members in Hamilton. It assessed the use and perceptions of the Extranet that had
      been built to support the committee during the SARS outbreak. Before
      distribution, the survey was user-tested based on a think-aloud protocol, and
      revisions were made. Quantitative and qualitative questions were asked related to
      frequency of use of the Extranet, perceived overall usefulness of the resource,
      rationale for use, potential barriers, strengths and limitations, and potential
      future uses of the Extranet. RESULTS: The response rate was 69.4% (n = 34). Of
      all respondents, 30 (88.2%) reported that they had visited the site, and rated it
      highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4
      compared with other communications strategies used during the outbreak. Almost
      half of all respondents (44.1%) visited the site at least once every few days.
      The two most common reasons the 30 respondents visited the Extranet were to
      access SARS Steering Committee minutes (63.3%) and to access Hamilton medical
      advisories (53.3%). The most commonly cited potential future uses for the
      Extranet were the sending of private emails to public health experts (63.3%), and
      surveillance (63.3%). No one encountered personal barriers in his or her use of
      the site, but several mentioned that time and duplication of email information
      were challenges. CONCLUSION: Despite higher rankings of various communication
      strategies during the SARS outbreak, such as email, meetings, teleconferences,
      and other web sites, users generally perceived a local Extranet as a useful
      support for the dissemination of local information during public health
      emergencies.

PMID- 15967042
TI  - Adenosine infusion increases plasma levels of VEGF in humans.
AB  - BACKGROUND: Many in vitro studies have shown that adenosine (Ado) can induce
      vascular endothelial growth factor (VEGF) mRNA and protein expression and
      stimulate endothelial proliferation. In the present study, we seek to determine
      whether Ado can increase circulating levels of VEGF protein in the intact human.
      METHODS: Five outpatients 49.3 +/- 6.7 years of age and weighing 88.2 +/- 8.5 kg
      were selected. They were given a 6 min intravenous infusion of Ado (0.14 mg kg-1
      min-1) in conjunction with sestamibi myocardial perfusion scans. Mean blood
      pressure (MBP, calculated from systolic and diastolic values) and heart rate (HR)
      were determined before Ado infusion and every 2 min for the next 10 min. Plasma
      VEGF concentrations (ELISA) were determined immediately before Ado infusion and 1
      h, 2 h, and 8 h after the infusion. RESULTS: Plasma VEGF concentration averaged
      20.3 +/- 2.0 pg ml-1 prior to Ado infusion, and increased to 62.7 +/- 18.1 pg ml
      1 at 1 h post- infusion (p < 0.01). VEGF plasma concentration returned to basal
      levels 2 h after infusion (23.3 +/- 3.4 pg ml-1). MBP averaged 116 +/- 7 mmHg and
      heart rate averaged 70 +/- 7 prior to Ado infusion. MBP decreased by a maximum of
      approximately 22% and HR increased by a maximum of approximately 17% during the
      infusion. CONCLUSION: We conclude from these preliminary findings that
      intravenous infusion of adenosine can increase plasma levels of VEGF in humans.

PMID- 15967043
TI  - P-cadherin expression and survival rate in oral squamous cell carcinoma: an
      immunohistochemical study.
AB  - BACKGROUND: P-cadherin (P-cad) is a transmembrane molecule involved in the cell
      cell adhesion and similar to E-cadherin (E-cad), but less investigated in
      oncology, especially in in vivo studies. Aims of the present study were to assess
      the prevalence of P-cad expression in oral squamous cell carcinoma (OSCC) and to
      verify whether P-cad can be considered a marker of prognosis in patients with
      OSCC. METHODS: In a retrospective study, a cohort of 67 OSCC patients was
      investigated for P-cad expression and its cellular localization by
      immunohistochemistry; some respective healthy margins of resection were similarly
      investigated as standard controls. After grouping for P-cad expression, OSCCs
      were statistically analyzed for the variables age, gender, histological grading
      (G), TNM, Staging, and overall survival rate. Univariate and multivariate
      analyses were performed. RESULTS: 37 cases (55.2%) of OSCC showed
      membranous/cytoplasmic positivity for P-cad, whereas 30 (44.8 %) were negative.
      Although with some differences in membranous vs cytoplasmic localization of P-cad
      in OSCC with different G, no statistical association was found between P-cad
      expression and any variables considered at baseline. In terms of prognostic
      significance, P-cad non expression was found to have an independent association
      with poorer overall survival rate than P-cad expressing group (P = 0.056);
      moreover, among P-cad +ve patients the best prognosis was for those OSCC with
      membranous (P < 0.0001) than those with cytoplasmic P-cad expression. CONCLUSION:
      On the basis of these results, it is possible to suggest P-cad as an early marker
      of poor prognosis. The abnormal or lack of P-cad expression could constitute an
      hallmark of aggressive biological behavior in OSCC.

PMID- 15967045
TI  - Chiropractic & Osteopathy. A new journal.
AB  - Both chiropractic and osteopathy are over a century old. They are now regarded as
      complementary health professions. There is an imperative for both professions to
      research the principles and claims that underpin them, and the new journal
      Chiropractic & Osteopathy provides a scientific forum for the publication of such
      research.

PMID- 15967044
TI  - The allergy adjuvant effect of particles - genetic factors influence antibody and
      cytokine responses.
AB  - BACKGROUND: There is increasing epidemiological and experimental evidence for an
      aggravating effect of particulate air pollution on asthma and allergic symptoms
      and, to a lesser extent, on allergic sensitization. Genetic factors appear to
      influence not only the magnitude, but also the quality of the adjuvant effect of
      particles with respect to allergen-specific IgE (Th2-associated) and IgG2a (Th1
      associated) responses. In the present study, we aimed to investigate how the
      genetic background influences the responses to the allergen and particles alone
      and in combination. We examined how polystyrene particles (PSP) affected the IgE
      and IgG2a responses against the model allergen ovalbumin (OVA), after
      subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN
      mice, Further, ex vivo IL-4, IFN-gamma and IL-10 cytokine secretion by Con A
      stimulated cells from the draining popliteal lymph node (PLN) five days after
      injection of OVA and PSP separately or in combination was determined. RESULTS:
      PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all
      strains examined. In contrast, the IgG2a levels were significantly increased only
      in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL
      4, IL-10 and IFN-gamma levels in BALB/cA, NIH and C3H/HeN mice, with the
      exception of IFN-gamma in NIH mice. However, each mouse strain had their unique
      pattern of response to OVA+PSP, OVA and PSP, and also their unique background
      cytokine response (i.e. the cytokine response in cells from mice injected with
      buffer only). CONCLUSION: Genetic factors (i.e. the strain of mice) influenced
      the susceptibility to the adjuvant effect of PSP on both secondary antibody
      responses and primary cellular responses in the lymph node, as well as the
      cellular responses to both OVA and PSP given separately. Interestingly, PSP alone
      induced cytokine responses in the lymph node in some of the mouse strains.
      Furthermore, we found that the ex vivo cytokine patterns did not predict the in
      vivo Th2- and Th1-associated antibody response patterns in the different mouse
      strains. The results indicate that insoluble particles act by increasing the
      inherent response to the allergen, and that the genetic background may determine
      whether an additional Th1-associated component is added to the response.

PMID- 15967046
TI  - The establishment of the Chiropractic & Osteopathic College of Australasia in
      Queensland (1996-2002).
AB  - INTRODUCTION: For chiropractors and osteopaths after graduation, the learning
      process continues by way of experience and continuing education (CE). The
      provision of CE and other vocational services in Queensland between 1996 and 2002
      is the subject of this paper. METHODS: The Chiropractic & Osteopathic College of
      Australasia (COCA) implemented a plan, which involved continuing education, with
      speakers from a broad variety of health provider areas; and the introduction of
      the concepts of evidence-based practice. The plan also involved building
      membership. RESULTS: Membership of COCA in Queensland grew from 3 in June 1996 to
      167 in 2002. There were a total of 25 COCA symposia in the same period. Evidence
      based health care was introduced and attendees were generally satisfied with the
      conferences. DISCUSSION: The development of a vocational body (COCA) for
      chiropractors and osteopaths in Queensland was achieved. Registrants in the field
      have supported an organisation that concentrates on the vocational aspects of
      their practice.

PMID- 15967047
TI  - Successful management of hamstring injuries in Australian Rules footballers: two
      case reports.
AB  - Hamstring injuries are the most prevalent injury in Australian Rules football.
      There is a lack of evidence based literature on the treatment, prevention and
      management of hamstring injuries, although it is agreed that the etiology is
      complicated and multi-factorial. We present two cases of hamstring injury that
      had full resolution after spinal manipulation and correction of lumbar-pelvic
      biomechanics. There was no recurrence through preventative treatment over a
      twelve and sixteen week period. The use of spinal manipulation for treatment or
      prevention of hamstring injury has not been documented in sports medicine
      literature and should be further investigated in prospective randomized
      controlled trials.

PMID- 15967048
TI  - Is obesity a risk factor for low back pain? An example of using the evidence to
      answer a clinical question.
AB  - BACKGROUND: Obesity as a causal factor for low back pain has been controversial
      with no definitive answer to this date. The objective of this study was to
      determine whether obesity is associated with low back pain. In addition this
      paper aims to provide a step-by-step guide for chiropractors and osteopaths on
      how to ask and answer a clinical question using the literature. METHODS: A
      literature review using the MEDLINE search engine using the keywords "obesity",
      "low back pain", "body mass index" "BMI" and "osteoarthritis" from years 1990 to
      2004 was utilised. The method employed is similar to that utilised by evidence
      based practice advocates. RESULTS: The available data at this time is
      controversial with no clear-cut evidence connecting low back pain with obesity.
      CONCLUSION: There is a lack of a clear dose-response relationship between body
      mass index (BMI) and low back pain. Further, studies on the relationship between
      obesity and related lumbar osteoarthritis, knee pain, and disc herniation are
      also problematic.There is little doubt that future studies with controlled
      variables are needed to determine the existence of an unambiguous link, if any.

PMID- 15967049
TI  - The biopsychosocial model and hypothyroidism.
AB  - This paper comments on the role and emergence of the biopsychosocial model in
      modern medical literature and health care settings. The evolution of the
      biopsychosocial model and its close association with modern pain theory is also
      examined. This paper seeks to discuss the place of this model with respect to the
      management of hypothyroidism. This discussion represents a forerunner to a
      randomised control trial that will seek to investigate the effect of a
      biopsychosocial-based treatment regime on hypothyroidism.

PMID- 15967051
TI  - Why a new online open access journal in the field of clinical and epidemiological
      research in mental health?
AB  - Clinical Practice and Epidemiology in Mental Health will encompass all aspects of
      clinical and epidemiological research in psychiatry and mental health, and will
      aim to build a bridge between clinical and epidemiological research. There are
      several outstanding mental heath journals covering all aspects of this dynamic
      field, but none of these journals is devoted to bridging clinical and
      epidemiological research. The Open Access online distribution of the journal and
      its inclusion in the leading data bases (such as PubMed Central) will ensure
      widespread and ready visibility, which are indispensable given the demand for
      immediate debate and comparison of scientific findings. This launch Editorial
      provides an overview of the field, and highlights some of the journal policies.

PMID- 15967050
TI  - Parasuicide and drug self-poisoning: analysis of the epidemiological and clinical
      variables of the patients admitted to the Poisoning Treatment Centre (CAV),
      Niguarda General Hospital, Milan.
AB  - Epidemiological knowledge of parasuicides and drug self-poisoning is still
      limited by a lack of data. A number of preliminary studies, which require further
      analysis, evidenced that parasuicidal acts occur more often among females, that
      the peak rate is generally recorded between the ages of 15 and 34 years and
      psychotropic medications seems to be the most frequently used. The aim of this
      study was to describe the demographic and clinical variables of a sample of
      subjects admitted to the Posisoning Treatment Centre (CAV), Niguarda General
      Hospital, Milan, following drug self-poisoning. Furthermore, this study is aimed
      to identify the risk factors associated to parasuicidal gestures, with special
      care for the used drugs, the presence of psychiatric or organic disorders,
      alcoholism and drug addiction.The study included the 201 patients attending the
      CAV in 1999 and 2000 who satisfied the criteria of self-poisoning attempts: 106
      cases in 1999 and 95 in 2000.The sample had a prevalence of females (64%). The
      peak rates of parasuicides from drug self-poisoning were reached between 21 and
      30 years among the females, and 31 and 40 years among the males. 81.6% of the
      patients used one or more psychoactive drugs, the most frequent being the
      benzodiazepines (58.7%), classic neuroleptics (16.9%) and new-generation
      antidepressants (SSRIs, SNRIs, NARIs) (12.9%). The prevalence of mood disorders
      was higher among females (64% vs 42%), whereas schizophrenia was more frequently
      diagnosed in males (22% vs 10%). 61% (33%) had a history of previous attempted
      suicides. The presence of clinically relevant organic diseases was observed in
      24.9% of the sample.

PMID- 15967052
TI  - Markov models of major depression for linking psychiatric epidemiology to
      clinical practice.
AB  - BACKGROUND: Most epidemiological studies of major depression report estimates of
      period prevalence. Such estimates are useful for public health applications, but
      are not very helpful for informing clinical practice. Period prevalence is
      determined predominantly by incidence and episode duration, but it is difficult
      to connect these epidemiological concepts to clinical issues such as risk and
      prognosis. Incidence is important for primary and secondary prevention, and
      prognostic information is useful for clinical decision-making. The objective of
      this study was to decompose period prevalence data for major depression into its
      constituent elements, thereby enhancing the value of these estimates for clinical
      practice. Data from a series of population-based Canadian studies were used in
      the analysis. Markov models depicting incidence, prevalence and recovery from
      major depressive episodes were developed. Monte Carlo simulation was used to
      constrain model parameters to the epidemiological data. RESULTS: The association
      of sex with major depression was found to be due to a higher incidence in women.
      In distinction, the higher prevalence in unmarried subjects was mostly due to a
      different prognosis. Age-related changes in prevalence were influenced by both
      factors. Education, which was not found to be associated with major depression in
      the survey data, had no impact either on risk or prognosis. CONCLUSION: The
      period prevalence of major depression is influenced both by incidence (risk) and
      episode duration (prognosis). Mathematical modeling of the underlying
      epidemiological relationships can make such data more readily interpretable in
      relation to clinical practice.

PMID- 15967053
TI  - Epidemiological and clinical aspects of bipolar disorders: controversies or a
      common need to redefine the aims and methodological aspects of surveys.
AB  - Data from surveys of large samples showed the lifetime prevalence rates of
      bipolar disorder around 1.5%. A main question is whether the low prevalence rates
      of bipolar disorders are not an artefact of the over-diagnosis of depression and
      under-diagnosis of bipolar-II.Analysis of the clinician's logical inferential
      diagnostic process, confirms that the patient does not represent the sole source
      of useful information because many patients do not experience hypomania as
      distress but rather as recovery from depression or as a period during which they
      felt truly well.Epidemiological data are derived from interviews carried out by
      lay staff which only reflect the patient's point of view.The clinical monitoring
      study carried out alongside the ESEMED project found for the diagnosis of mood
      disorders, a Kappa agreement (versus clinical interview) which ranged from 0.23
      in Spain to 0.49 in France.If we consider exactly what a Kappa of 0.4 implies for
      a disorder with an "identified" prevalence rate of 2%, we discover that the
      prevalence rate may have been under-diagnosed approximately 1.5-fold, so 67% of
      cases may not have been identified and 50% of the identified cases may be false
      positives.It is legitimate to surmise that the prevalence reported by recent
      (extremely costly) epidemiological surveys may be doubtful.Which direction should
      epidemiology take in dealing with the serious matter of bipolar
      disorders?Recently, some community surveys were carried out in the USA using the
      Mood Disorder Questionnaire. In the ensuing debate, one side claimed that the
      instrument was scarcely accurate when used in the general population, gave rise
      to numerous false positives and that the high prevalence reported was therefore a
      mere artefact. The other side defended the results reported by the research
      studies, on the basis that "positive" cases were homogeneous with regard to the
      high level of subjective distress, low social functioning and employment and with
      the high recourse to health care structures.It is quite probable that the problem
      lies at the root of the matter, in the definition of the gold standard.In the
      present state of our knowledge on course and response to treatment, the current
      diagnostic thresholds applied for mixed states and hypomanic episodes seem to be
      unsatisfactory.It is inconceivable that the diagnostic gold standard should be
      determined only on the basis of a structured interview of patients alone. But
      unless there is clinical consensus on the diagnostic threshold for hypomania and
      mixed states, there can be no consensus on the findings of epidemiological
      research.

PMID- 15967054
TI  - Violence, misconduct and schizophrenia: Outcome after four years of optimal
      treatment.
AB  - BACKGROUND: Aggressive behaviour in patients with schizophrenic disorders is an
      ongoing source of concern to community-based services. It has been suggested that
      optimal treatment may reduce the risk of serious misconduct. OBJECTIVE: To assess
      prospectively aggressive and sexual misconduct in a cohort of patients receiving
      continued evidence-based community treatment. METHOD: Fifty patients with a DSM
      IV diagnosis of a schizophrenic disorder were treated for 4 years with integrated
      biomedical and psychosocial strategies. The frequency and context of all
      aggressive and sexually inappropriate behaviour were assessed throughout.
      Correlations between an index of misconduct and demographic and clinical
      variables were examined. RESULTS: Levels of serious misconduct were low at the
      start of the project and declined as treatment progressed. Close examination of
      predictors of misconduct supported larger epidemiological studies imputing
      persistent psychotic symptoms, personality disorders and substance use.
      CONCLUSION: The study supports the hypothesis that effective treatment reduces
      aggressive and sexual misconduct in schizophrenic disorders.

PMID- 15967055
TI  - Psychosocial factors and their role in chronic pain: A brief review of
      development and current status.
AB  - The belief that pain is a direct result of tissue damage has dominated medical
      thinking since the mid 20th Century. Several schools of psychological thought
      proffered linear causal models to explain non-physical pain observations such as
      phantom limb pain and the effects of placebo interventions. Psychological
      research has focused on identifying those people with acute pain who are at risk
      of transitioning into chronic and disabling pain, in the hope of producing better
      outcomes.Several multicausal Cognitive Behavioural models dominate the research
      landscape in this area. They are gaining wider acceptance and some aspects are
      being integrated and implemented into a number of health care systems. The most
      notable of these is the concept of Yellow Flags. The research to validate the
      veracity of such programs has not yet been established.In this paper I seek to
      briefly summarize the development of psychological thought, both past and
      present, then review current cognitive-behavioural models and the available
      supporting evidence. I conclude by discussing these factors and identifying those
      that have been shown to be reliable predictors of chronicity and those that may
      hold promise for the future.

PMID- 15967056
TI  - Heterozygous beta-thalassaemia as a susceptibility factor in mood disorders:
      excessive prevalence in bipolar patients.
AB  - BACKGROUND: Previous preliminary reports have suggested potential interactions
      between microcytic anaemia and mood disorders. In particular, heterozygous beta
      thalassaemia has been implicated in the bipolar spectrum. This study surveyed
      relevant haematological parameters in a large sample of psychiatric outpatients
      with the aim of clarifying previous observations. METHODS: Mean Corpuscular
      Volume (MCV) was analysed in 1014 consecutive patients diagnosed according to
      modified Research Diagnostic Criteria (RDC). Haemoglobin electrophoresis and/or
      chromatography was performed in blood samples from 143 patients with reduced MCV.
      Prevalence of heterozygous beta-thalassaemia was estimated based on the rates of
      patients with reduced MCV and increased haemoglobin A2 concentration. RESULTS:
      MCV lower than 80 mu3 was found in greater proportions among bipolar compared
      with the remaining RDC subgroups (183/732 = 25.0% versus 51/282 = 18.1%; p =
      0.02; relative risk = 1.38; Fisher's exact test). This difference can mainly be
      attributed to heterozygous beta-thalassaemia, the estimated prevalence of which
      was 16.4% among bipolar and 9.9% among non-bipolar subgroups (p = 0.01; relative
      risk = 1.65). CONCLUSION: The results are consistent with the hypothesis that
      heterozygous beta-thalassaemia might play a role as a susceptibility factor in
      bipolar spectrum disorders in specific populations.

PMID- 15967057
TI  - Regulation of pro-inflammatory signalling networks by ubiquitin: identification
      of novel targets for anti-inflammatory drugs.
AB  - Modification of cellular proteins with a small protein called ubiquitin has
      profound effects on their activities. Ubiquitin is covalently attached to lysine
      residues of acceptor proteins through the concerted action of E1 ubiquitin
      activating enzyme, E2 ubiquitin-carrier proteins and E3 ligases. Mammalian cells
      contain a large number of E3 ligases, which determine the specificity of
      ubiquitination reactions. Recent studies have revealed that ubiquitination can be
      reversed by deubiquitinating enzymes that release ubiquitin monomers from
      modified proteins. Signalling networks that control inflammation are tightly
      regulated by a multitude of ubiquitination and deubiquitination reactions. This
      article begins by summarising current understanding of these pathways at a
      molecular level, and then focuses on the importance of ubiquitination and
      deubiquitination during the regulation of the pro-inflammatory transcription
      factor NF-kappaB. Finally, the potential for ubiquitin modifications to be
      targeted by novel classes of anti-inflammatory drugs is discussed.

PMID- 15967058
TI  - Can biological tests assist prediction of suicide in mood disorders?
AB  - Predicting suicide is difficult due to its low base-rate and the limited
      specificity of clinical predictors. Prospective biological studies suggest that
      dysfunctions in the serotonergic system and hypothalamic-pituitary-adrenal axis
      have some predictive power for completed suicide in mood disorders. A prediction
      model that incorporates biological testing to increase specificity and
      sensitivity of prediction of suicide is of potential clinical value. Meta
      analyses of prospective biological studies of suicide and cerebrospinal fluid 5
      hydroxyindoleacetic acid (CSF 5-HIAA) and suicide and the dexamethasone
      suppression test (DST) in mood disorders using the penalized quasi-likelihood
      (PQL) and bootstrap method yield odds ratios for prediction of suicide of 4.48
      and 4.65 respectively. Two combinatory prediction models, the first requiring
      positive results on more than one test, and the second requiring a positive
      result on either one of two tests, were tested to assess their sensitivity,
      specificity, and predictive power using biological data from published and
      unpublished studies. The prediction model that requires both DST and CSF 5-HIAA
      tests to be positive results in 37.5% sensitivity, 88% specificity, and has a
      positive predictive value of 23%. The prediction model that requires either DST
      or CSF 5-HIAA tests to be positive results in 87.5% sensitivity, 28% specificity,
      and has a positive predictive value of 10%. Thus, models attempting to predict a
      lethal outcome that is uncommon perform very differently making model choice of
      major importance. Further work on refining biological predictors and integration
      with clinical predictors is needed to optimize a model to predict suicide in the
      clinic.

PMID- 15967059
TI  - Altered responsiveness of serotonin receptor subtypes following long-term
      cannabinoid treatment.
AB  - This study examined the effects of long-term cannabinoid administration on the
      responsivity of 5-HT1A and 5-HT2A receptors, which have been implicated in
      depression. Animals received 12 d administration of the potent cannabinoid
      receptor agonist HU-210 (100 microg/kg), following which they were monitored on
      their behavioural, physiological and hormonal responses to a single challenge of
      a 5-HT1A and 5-HT2A receptor agonist, 8-OH-DPAT (0.3 mg/kg) and DOI (1 mg/kg)
      respectively. Chronic HU-210 treatment lead to a significant enhancement of DOI
      induced wet-dog shakes, but a reduction of DOI-induced back muscle contractions.
      DOI-induced corticosterone release was unaffected by HU-210 treatment. The
      hyperthermic response to DOI appeared to be potentiated by long-term HU-210
      treatment, as 50% of these subjects died from an apparent serotonin syndrome with
      core temperatures exceeding 43 degrees C. The 8-OH-DPAT-induced hypothermic
      response and elevation of corticosterone were both significantly attenuated by
      long- term HU-210 treatment. These data imply that chronic cannabinoid treatment
      may up-regulate 5-HT2A receptor activity while concurrently down-regulating 5
      HT1A receptor activity, a finding similar to that sometimes observed in
      depression. This may partially explain the association between excessive cannabis
      consumption and the induction of affective disease.

PMID- 15967060
TI  - Effects of chronic administration of olanzapine, amitriptyline, haloperidol or
      sodium valproate in naive and anhedonic rats.
AB  - Although in bipolar patients the main therapeutic indication of atypical
      antipsychotics is the management of acute mania, several observations suggest
      that these agents may exert antidepressant as well as anti-manic effects. The
      main goal of the present work was to evaluate the putative antidepressant effect
      of chronic olanzapine (Ola) (0.02-0.1 or 0.5 mg/kg.d), in comparison to
      haloperidol (Hal) (0.2 mg/kg.d) and sodium valproate (VPA) (5 or 30 mg/kg.d), in
      rats exposed to a protocol of chronic mild stress. The tricyclic compound
      amitriptyline (Ami) (5 mg/kg.d) was used as reference drug. The results indicate
      that Ola, in a rodent model of depression, has protective effects against the
      stress-induced anhedonia. Compared to Hal and VPA, Ola shows a greater
      antidepressant activity and is as effective as Ami in preventing the anhedonic
      state. The effects of Ola and Ami, however, have a different time-course. A full
      reversion of the anhedonia by Ami appears after a latency of 4 wk, whereas the
      effect of Ola is already evident 1 wk after the beginning of the chronic
      treatment. Moreover, the recovery from anhedonia at the end of the stress
      protocol and after drug cessation was more rapid in groups of rats pretreated
      with Ola or VPA than in the group of saline-pretreated rats. In conclusion, the
      results indicate that 0.02 mg/kg.d Ola causes a rapid and sustained
      antidepressant-like effect, while all other anti-manic treatments show loss of
      efficacy at 3 wk. Taken together, these observations support the hypothesis that
      Ola has a broader pharmacotherapeutic profile than solely as an antipsychotic or
      anti-manic agent.

PMID- 15967061
TI  - The effect of chronic co-administration of fluvoxamine and haloperidol compared
      to clozapine on the GABA system in the rat frontal cortex.
AB  - Clinical studies in schizophrenia patients have shown that adding a selective
      serotonin reuptake inhibitor (SSRI) to antipsychotics can ameliorate negative
      symptoms that frequently resist standard treatments. It has been proposed that
      this combined treatment produces a 'net effect', different from that of the
      individual drugs and possibly common to that of the atypical antipsychotic,
      clozapine, which also ameliorates negative symptoms. The present study was
      initiated to determine the molecular events in the rat frontal cortex resulting
      from combined treatment of fluvoxamine and haloperidol compared to clozapine.
      Rats were allocated to five groups and received a daily intraperitoneal injection
      with one of the following: haloperidol (1 mg/kg), fluvoxamine (11 mg/kg),
      clozapine (11 mg/kg), haloperidol (1 mg/kg) plus fluvoxamine (11 mg/kg), or
      vehicle for 30 d. cDNA arrays were used to screen a broad range of genes in the
      frontal cortex. Several of the most prominent alterations were taken for analysis
      in real-time RT-PCR and their related proteins were examined by the Western
      blotting technique. The gene expression profile of the combined fluvoxamine plus
      haloperidol treatment was different from that of the individual drugs. Moreover,
      clozapine showed some degree of homology with the dual treatment. The protein
      expression changes, specific to the combined treatment, included glutamic acid
      decarboxylase (GAD67) and protein kinase Cbeta (PKCbeta). The latter showed a
      similar trend following clozapine treatment. The present findings support the
      existence of a unique mechanism for SSRI-antipsychotic combination, different
      from that of the individual drugs and suggest that it may involve modification of
      the gamma aminobutyric acid (GABA) system.

PMID- 15967062
TI  - Asymptomatic reboxetine overdose.

PMID- 15967063
TI  - A NOS-III haplotype that includes functional polymorphisms is associated with
      bipolar disorder.
AB  - The pleiotropic messenger molecule nitric oxide (NO) has been implicated in a
      variety of higher CNS functions, including learning, memory, and emotionality. In
      the human brain, NO is predominantly formed by neuronal NO synthase (NOS-I),
      while the so-called 'endothelial' isoform NOS-III also contributes to NO
      generation. We recently reported that NOS-III knockout mice display decreased
      adult neurogenesis and reduced responsiveness in a learned helplessness paradigm.
      To examine whether NOS-III plays a role in affective disorders as well, we tested
      a NOS-III gene haplotype, consisting of three functional polymorphisms, for an
      association with bipolar disorder and major depression. A significant global
      haplotype association with bipolar disorder (n = 284 controls; n = 91 patients;
      p(global) = 0.021; p(t-a-g) < 0.001), but not unipolar depression (n = 45) was
      detected. Our results thus suggest that the NOS-III genotype may convey a modest
      genetic risk to develop bipolar disorder. This finding should be further
      clarified by the use of within-family designs and in samples of other ethnicity.

PMID- 15967064
TI  - Clinical management of eosinophilic gastrointestinal disorders.

PMID- 15967067
TI  - Basophils and mast cells in chronic idiopathic urticaria.
AB  - Chronic idiopathic urticaria (CIU) is diagnosed in patients when urticarial
      eruptions recur for more than 6 weeks, and no specific cause is determined. Given
      that urticaria resembles the lesions induced by injection of histamine or
      allergen into the skin, a role for mast cells or basophils has been proposed in
      the generation of localized urticarial lesions. However, currently, the exact
      mechanisms governing regional mast cell or basophil activation are unknown. In
      the past decade, there has been mounting interest in viewing CIU as an autoimmune
      disease, given the presence of circulating autoantibodies to IgE or the alpha
      subunit of the high-affinity IgE receptor (FceRI) in a subset of patients. In
      this review, we propose that in addition to autoantibodies, specific differences
      in the expression of FceRI-signaling molecules in the basophils or mast cells of
      CIU patients may contribute to the generation of urticarial eruptions.

PMID- 15967068
TI  - Mechanism of chronic urticaria exacerbation by aspirin.
AB  - In some patients with chronic idiopathic urticaria (CIU), aspirin and other
      nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase 1 (COX
      1) precipitate wheals and swelling. There is no in vitro diagnostic, and
      diagnosis can be established only by provocation challenges with aspirin or other
      NSAIDs. Skin reactions triggered by aspirin are associated with the inhibition of
      cyclooxygenase, specifically COX-1, but not COX-2, and are characterized by
      overproduction of cysteinyl leukotrienes (cys-LTs). Aspirin and other NSAIDs
      should be avoided, but highly specific COX-2 inhibitors, known as coxibs, are
      well tolerated and can probably be safely used. Evidence has been accumulated
      that these reactions are due to the interference of aspirin-like drugs with
      arachidonic-acid metabolism. In this article, we discuss the mechanism of these
      reactions, and the characteristic course of aspirin-induced urticaria and its
      management.

PMID- 15967069
TI  - Chemokine networks in atopic dermatitis: traffic signals of disease.
AB  - Atopic dermatitis is a chronic or chronically relapsing inflammatory skin disease
      with a prevalence ranging from 10% to 20% in children and 1% to 3% in adults of
      developed countries. Skin-infiltrating leukocytes play a pivotal role in the
      initiation and amplification of atopic skin inflammation. Recent studies
      demonstrated that infiltration of inflammatory cells into tissues is regulated by
      chemokines. A subset of chemokines including CCL27, CCL17, CCL22, CCL18, CCL11,
      and CCL13 are highly expressed in atopic dermatitis. The corresponding chemokine
      receptors are found on the main leukocyte subsets involved in allergic skin
      inflammation, such as T cells, eosinophils, and dendritic cells. In this article,
      we provide an overview of the role of chemokines in the complex
      immunopathogenesis of atopic dermatitis, highlighting potential areas for
      therapeutic intervention.

PMID- 15967070
TI  - Lessons from murine models of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a complex disease that manifests immunologic
      abnormalities in the skin. The immunologic changes of AD are characterized by a T
      helper cell type 2 (Th2)-dominated immune response in its acute phase and a
      Th1/Th2 mixed immune response in its chronic phase. Although the clinical
      presentation and pathologic changes are initially in the skin, AD may be, in
      part, a systemic disorder. In fact, AD is often considered to be the initial
      manifestation of the "atopic march" that progresses from AD to allergic rhinitis
      and asthma. In the past several years, a number of murine models of AD have been
      developed or discovered, and studies on these models have contributed greatly to
      our understanding of the immunopathogenesis of this disease. This review is
      focused on these recent, illuminating advances in animal models of AD.

PMID- 15967072
TI  - Immunologic screening of children with recurrent otitis media.
AB  - Some 5% to 10% of all infants and toddlers suffer from four or more episodes of
      otitis per year. Usually, this is a temporary problem that resolves with
      increasing age. In a minority of cases, otitis episodes are frequent or have an
      abnormal course, with complications such as mastoiditis. In these cases,
      immunologic screening is indicated, to exclude an immunodeficiency.
      Agammaglobulinemia or hypogammaglobulinemia is rare among these patients. Other
      immune defects that occur more often are deficient or lowered immunoglobulin
      (Ig)A or decreased levels of one or more IgG subclass, in particular IgG2. The
      specific antibody response to bacterial capsular polysaccharides often is
      disturbed. These findings can give direction to the treatment of children with
      frequent, recurrent otitis.

PMID- 15967073
TI  - Complications of acute otitis media in children.
AB  - The clinical picture and the treatment of acute otitis media (AOM) and its
      complications have changed during the past decades. The availability of
      antibiotics has decreased the incidence of complications of AOM significantly.
      The treatment of complications of AOM is conservative in most cases.
      Mastoidectomy is needed when abscess-forming mastoiditis or intracranial
      complications develop. Although intratemporal and intracranial complications of
      AOM are rare today, they still cause morbidity, and need prompt treatment.
      Occasionally, permanent damage of the ear leads to hearing loss, vertigo, and
      sometimes, facial weakness. Antibiotic treatment has decreased the mortality
      associated with the complications of AOM, but it is still high in countries with
      developing health care systems. Early diagnosis and effective treatment of the
      complications are the bases for a good prognosis.

PMID- 15967074
TI  - Complementary and alternative medicine in allergy, otitis media, and asthma.
AB  - There is growing interest on the part of both patients and providers in the use
      of complementary and alternative medicine (CAM) therapies to treat allergy,
      otitis media, and asthma. Research efforts investigating CAM are increasing in
      frequency and quality. Studies suggest possible efficacy for some vitamin and
      mineral supplements for allergic diseases; results are less clear in asthmatic
      patients. The use of polyunsaturated fatty acids appears particularly promising
      for treatment and even prevention of allergy and asthma conditions. Studies also
      suggest that probiotic preparations have a role in the treatment of allergic
      conditions. Xylitol gum, syrup, and lozenges have shown efficacy in treatment of
      acute otitis media, as have some naturopathic herbal remedies. Preliminary
      results with studies of yoga and various relaxation therapies for treatment of
      asthmatics suggest that these therapies may have a role, but further work would
      be needed to document efficacy and delineate the specific types of interventions
      most appropriate for particular asthmatic populations.

PMID- 15967077
TI  - Ocular involvement in connective tissue disorders.
AB  - Connective tissue disorders have well-known ocular associations that may be
      presenting features of the disease or occur as complications during the course of
      the disorder. Keratoconjunctivitis sicca, keratitis, scleritis, uveitis, retinal
      vasculitis, choroidopathy, and their associations with rheumatoid arthritis,
      systemic lupus erythematosus, systemic sclerosis, psoriatic arthritis, juvenile
      idiopathic arthritis, and polymyositis are reviewed.

PMID- 15967078
TI  - Recent advances in the management of ocular complications of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disorder, the principal ocular
      manifestation of which is decreased tear production leading to chronic irritation
      and damage to the corneal and conjunctival epithelium. The most important advance
      in the treatment of ocular manifestations of SS is the introduction of topical
      anti-inflammatory agents such as cyclosporine A, which increases tear production
      and decreases symptoms without any significant side effect. Stimulators of tear
      secretion, both topical, such as diquafosol, and systemic, such as pilocarpine
      and cevimeline, are also effective, although they have been associated with
      frequent side effects. Topical use of autologous serum is another new and
      effective form of treatment, but problems in the preparations prevent their
      widespread use. Additionally, nonpharmacologic treatments, such as insertion of
      punctal plugs, are beneficial in the dry eye of SS, whereas several other
      modalities, such as anti-CD4 monoclonal antibody eye drops and gene transfer, are
      still in experimental phases.

PMID- 15967079
TI  - Ocular cicatricial pemphigoid: manifestations and management.
AB  - Ocular cicatricial pemphigoid (OCP) is a chronic, progressive cicatrizing
      inflammatory disease of presumed autoimmune etiology affecting the mucous
      membranes and skin. It has sight-threatening ocular manifestations and
      potentially life-threatening extraocular manifestations. The ocular signs
      include: chronic cicatricial conjunctivitis, progressive conjunctival fibrosis,
      and corneal epitheliopathy. Systemic immunomodulatory therapy is the treatment of
      choice for controlling disease activity and limiting progression, given the
      systemic nature of the disease and the poor efficacy of current local or topical
      therapies. Systemic cyclophosphamide with short-term adjunctive high-dose
      prednisolone is the preferred treatment for severe and/or rapidly progressing
      OCP. Oral low-dose weekly methotrexate is a useful first-line treatment for mild
      to-moderate OCP. The management of OCP requires a multidisciplinary approach to
      optimize the care of these patients.

PMID- 15967080
TI  - Molecular prognostic factors in diffuse large B-cell lymphoma.
AB  - The treatment of patients with diffuse large B-cell lymphoma (DLBCL) has been
      guided traditionally by clinical parameters such as the Ann Arbor Staging
      Classification for Hodgkin's disease. Although the International Prognostic Index
      (IPI) represents the most widely accepted prognostic model, there is still a
      marked variability in outcome within identical IPI subgroups, reflecting the
      heterogeneity of this malignancy. Use of DNA microarray, real-time reverse
      transcription polymerase chain reaction, and tissue array immunohistochemistry
      methodologies makes the development of new classifications possible based on
      molecular profiling. The molecular classification of DLBCL may lead to the
      grouping of specific disease entities sharing similar biologic features, clinical
      behavior, and outcome. Once tested and validated, this new generation of
      prognostic models should become an integral part of the daily practice, providing
      valuable additional information to the currently existing clinically based
      predictive models. To accomplish these goals and to be in a position in which
      existing or new prognostic models can be easily tested and validated, there is a
      strong need to collect frozen and paraffin-embedded material that can be used for
      RNA extraction and construction of tissue arrays, respectively. Such materials
      should be gathered as an integral part of any planned study.

PMID- 15967081
TI  - Therapeutic options for patients with Hodgkin's disease and non-Hodgkin's
      lymphoma who relapse after autologous transplant.
AB  - Although autologous stem cell transplantation for Hodgkin's disease and non
      Hodgkin's lymphoma has become a safe and effective therapy, relapses after
      transplant are common. Emerging data indicate that an increasing number of
      patients can be re-induced into durable complete remission. Conventional dose-
      salvage chemotherapy and single-agent monoclonal antibody treatment provided
      limited success, but combination chemotherapy-monoclonal antibody treatments,
      second autografts, and reduced-intensity conditioning allografts provide
      encouraging results. For some patients, the best strategy may consist of
      participation in phase I to II studies of novel agents. New strategies designed
      to prevent relapse after autograft include cytokine therapy such as interleukin-2
      in combination with monoclonal antibodies and the use of autologous antilymphoma
      vaccines.

PMID- 15967082
TI  - Motexafin gadolinium induces oxidative stress and apoptosis in hematologic
      malignancies.
AB  - Redox mechanisms have been shown to be important in malignant cell survival and
      are a system that may be modified for the treatment of hematologic malignancies.
      Motexafin gadolinium (MGd) is a synthetic expanded porphyrin that selectively
      accumulates in tumor cells and oxidizes various intracellular metabolites,
      including ascorbate, nicotinamide adenine dinucleotide phosphate, glutathione,
      and protein thiols, to generate reactive oxygen species in a process known as
      futile redox cycling. The rationale for its use in hematologic malignancies is
      that, like naturally occurring porphyrins, it tends to concentrate selectively in
      cancer cells, and it has a novel mechanism of action of inducing redox stress and
      triggering apoptosis in a broad range of malignancies. MGd induces apoptosis in B
      cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and highly resistant
      myeloma cell lines. Furthermore, MGd is additive or synergistic with ionizing
      radiation, several chemotherapy agents, and rituximab in vitro and in vivo tumor
      models. Through gene expression profiling, various stress-related genes are
      upregulated in response to MGd, including genes encoding metallothioneins, heat
      shock proteins, and heme oxygenase. Preliminary results from clinical trials with
      MGd in hematopoietic malignancies have shown that it is well tolerated, with
      minimal hematologic side effects in both; it has single agent activity in very
      heavily pretreated chronic lymphocytic leukemia /small lymphocytic lymphoma
      patients, and it has induced prompt complete remissions in combination with
      90Yttrium-ibritumomab (Y-90 Zevalin; Biogen Idec Inc., Cambridge, MA) for
      relapsed non-Hodgkin's lymphoma in the first two cohorts of patients enrolled.
      Various clinical trials studying MGd as a single agent and in combination with
      radiation and/or chemotherapy for the treatment of hematologic malignancies are
      ongoing.

PMID- 15967083
TI  - Follicular lymphoma: management options in the era of targeted therapy.
AB  - For the vast majority of patients diagnosed with follicular lymphoma, the disease
      is never cured. As a result, it becomes a "chronic disease" that must be managed
      over many years. A wide array of management options exist, and it is difficult to
      claim that one strategy is better than another. It remains to be proven that a
      particular initial therapy or a particular sequence of therapies is superior, if
      one defines "superior" as affecting survival. It also remains to be proven that
      immediate treatment is superior to a "watch and wait" approach in patients with
      low tumor burden. However, newer targeted approaches to treatment are providing
      additional treatment options, and they generally have more favorable side-effect
      profiles than traditional cytotoxic therapies. The challenge is determining how
      to best incorporate such targeted therapies into traditional treatment.
      Additionally, determining the true impact of newer therapies is not entirely
      straightforward, as selection bias often confounds trial results in follicular
      lymphoma. A new follicular lymphoma prognostic index should aid in the
      interpretation of future clinical trials.

PMID- 15967084
TI  - Papillary thyroid cancer: surgical management of lymph node metastases.
AB  - Papillary thyroid cancer (PTC), the most common thyroid malignancy, is associated
      with cervical lymph node metastases in 30% to 90% of patients. While surgery is
      the primary treatment modality for PTC, radioactive iodine and thyroid hormone
      suppression often complement the treatment plan. Although thyroid hormone
      suppression may decrease the incidence of recurrent disease and radioactive
      iodine may diagnose and treat metastases, lymph node dissection (LND) is the
      mainstay treatment for clinically evident cervical lymph node metastases. The
      surgical treatment options published in the literature include the traditional
      radical LND, the modified radical LND, the selective LND (compartment-based
      resection based on documented lymph node metastases), and a 'berry picking'
      resection (in which only the grossly abnormal lymph nodes are excised). At the
      University of California, San Francisco, we prefer the modified radical LND with
      preservation of the cervical sensory nerves for the first lymph node dissection
      with the 'berry picking' procedure limited to surgical treatment of recurrent
      nodal metastases in previously resected lymph node basins. Some centers are
      evaluating the potential role of sentinel lymph node biopsies for PTC. While the
      extent of lymphadenectomy is debated, most physicians treating patients with PTC
      agree that clinical evidence of lymphatic metastases should be surgically
      exercised and there is no role for prophylactic LND.

PMID- 15967085
TI  - Papillary thyroid cancer: medical management and follow-up.
AB  - The incidence of epithelial derived thyroid cancer (papillary thyroid cancer and
      follicular thyroid cancer, known collectively as differentiated thyroid cancer)
      is rising. About 80% of patients with thyroid cancer have PTC and are best
      treated with thyroidectomy and functional lymph node dissection, followed by
      radioiodine ablation or therapy and performance of a posttreatment whole-body
      scan, followed by thyroid stimulating hormone (TSH) suppression. One year after
      radioiodine administration, the use of sensitive thyroglobulin (Tg) assays can
      separate the vast majority of patients with persistent disease from those who are
      free of disease and unlikely to have recurrent disease all without the need for
      repeat whole-body radioiodine imaging. Patients with detectable serum Tg during
      TSH suppression (Tg-on) or Tg that rises above 2 ng/mL after TSH stimulation (TSH
      Tg) are highly likely to harbor residual tumor. TSH stimulation can be achieved
      using either thyroid hormone withdrawal or recombinant human TSH (rhTSH). Highly
      skilled screening neck ultrasonography can identify a few additional patients
      with subcentimeter residual neck lymph node metastases not detected by TSH-Tg.
      However, ultrasonography and chest computed tomography (CT) are most critical for
      tumor localization in those patients with Tg values that suggest residual disease
      or in those patients with persistent antithyroglobulin antibodies (TgAb) that
      falsely lower Tg measurement. TgAb quantitative titers typically resolve steadily
      over just a few years in patients free of disease after initial therapy. Another
      paradigm shift is the recognition that most patients who eventually achieve
      freedom from disease do so by surgery with fewer patients cured by repetitive
      radioiodine treatments, and even fewer cured with external beam radiation.
      Patients who appear to be free of disease require a lifetime of follow-up to
      optimize levothyroxine treatment, and they will undergo periodic stimulation
      testing because some will still manifest recurrent disease. Patients with
      persistent disease despite negative ultrasonography, chest CT, and whole-body
      radioiodine imaging may have a tumor identified by fluorodeoxyglucose positron
      emission tomography, optimally performed with combined TSH stimulation and image
      fusion with CT or magnetic resonance imaging. Patients with metastatic disease
      who are unresponsive to conventional treatment are encouraged to participate in
      increasingly available thyroid cancer-specific clinical trials using targeted
      experimental oral or intravenous chemotherapeutic agents to address this tumor
      that has historically proven resistant to conventional chemotherapeutic agents.

PMID- 15967086
TI  - Medullary thyroid cancer: medical management and follow-up.
AB  - Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy that occurs in
      hereditary (25%) and sporadic (75%) clinical settings. MTC is present in all
      patients with the multiple endocrine neoplasia type 2 (MEN 2) syndromes. MTCs
      produce calcitonin, measurement of which indicates the presence of tumor in at
      risk individuals and the effectiveness of therapy in treated patients. Surgery is
      the mainstay of therapy for primary and recurrent disease. Routine serial
      postoperative measurement of calcitonin levels should be done. Patients with
      elevated calcitonin levels should have imaging by computed tomography scan,
      magnetic resonance imaging, and/or fluorodeoxyglucose positron emission
      tomography to identify sites of recurrence and metastasis. The role of radiation
      therapy is not well defined. There is no effective systemic therapy for MTC at
      present. Activating mutations in a tyrosine kinase receptor gene are present in
      the majority of MTCs, and experience with tyrosine kinase inhibitors and other
      agents in the setting of clinical trials is critical for the identification of
      effective systemic treatment.

PMID- 15967087
TI  - Medullary thyroid carcinoma: management of lymph node metastases.
AB  - Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C
      cells. Spread of MTC commonly occurs to cervical and mediastinal lymph nodes. MTC
      cells do not concentrate radioactive iodine, and are not sensitive to hormonal
      manipulation. Because of these features, the treatment of metastatic or recurrent
      MTC is different from the treatment of differentiated thyroid cancer. Surgery is
      the only effective therapy at present that can result in cure, or reduction in
      tumor burden, or effective palliation. Systematic surgical removal of at-risk or
      involved lymph node basins should be done in patients with palpable primary
      tumors and recurrence. A "berry-picking" approach is discouraged. Although data
      are limited, standard chemotherapy and radiation therapy have not been effective
      in the treatment of MTC. Newer targeted drug therapies are being examined in
      therapeutic clinical trials.

PMID- 15967088
TI  - Treatment of Convulsive and Nonconvulsive Status Epilepticus.
AB  - Status epilepticus (SE) should be treated as quickly as possible with full doses
      of medications as detailed in a written hospital protocol. Lorazepam is the drug
      of choice for initial treatment. If intravenous access is not immediately
      available, then rectal diazepam or nasal or buccal midazolam should be given.
      Prehospital treatment of seizures by emergency personnel is effective and safe,
      and may prevent cases of refractory SE. Home treatment of prolonged seizures or
      clusters with buccal, nasal, or rectal benzodiazepines should be considered for
      all at-risk patients. Nonconvulsive SE is underdiagnosed. An electroencephalogram
      should be obtained immediately in anyone with unexplained alteration of behavior
      or mental status and after convulsive SE if the patient does not rapidly awaken.
      Delay in diagnosis of SE is associated with a worse outcome and a higher
      likelihood of poor response to treatment. For refractory SE, continuous
      intravenous midazolam and propofol (alone or in combination) are rapidly
      effective. Randomized trials are needed to determine the best treatment for SE
      after lorazepam.

PMID- 15967089
TI  - Experimental Electrical Stimulation Therapy for Epilepsy.
AB  - Electrical stimulation of the nervous system is an attractive possible therapy
      for intractable epilepsy, but only stimulation of the vagus nerve has been
      subjected to large, controlled, and completed clinical trials. Controlled trials
      are in progress for intermittent cycling stimulation of the anterior nuclei of
      the thalamus, and for cortical stimulation at a seizure focus, responsive to
      detection of seizure onset. Anecdotal experience has been gathered with
      stimulation of cerebellum, centromedian thalamus, subthalamus, caudate,
      hippocampus, and brainstem. All stimulation of the central nervous system for
      epilepsy must be considered experimental.

PMID- 15967090
TI  - Effects of Treatment on Endocrine Function in Patients with Epilepsy.
AB  - Antiepileptic drug (AED) treatment is associated with multiple short- and long
      term side effects. Effects on endocrine function, including weight change,
      reproductive function, thyroid function, and bone health are examples of these
      side effects. Some AEDs affect weight, resulting in weight gain or loss.
      Levetiracetam and lamotrigine are weight-neutral agents, whereas valproate is
      associated with weight gain. Reproductive dysfunction is reported in women and
      men with epilepsy treated with AEDs. In women, the most common symptoms are
      hyperandrogenism, menstrual disorders with ovulatory failure, polycystic ovary
      appearing ovaries or polycystic ovary syndrome, and hyperinsulinemia. These
      symptoms may be secondary to epilepsy or to AED treatment, particularly with
      valproate. In men, effects on sperm quality and motility, delayed sexual
      development, and small testicular size have been described in association with
      AED treatment. Carbamazepine reduces testosterone levels, whereas valproate
      increases androgen levels. Oxcarbazepine is not associated with changes in
      testosterone levels. Treatment with all of these agents can result in changes in
      sperm, including concentration, morphology, and motility. Enzyme-inducing AEDs
      are known to result in decreased thyroid hormones. Recent studies found reduced
      serum thyroid hormone concentrations in men and young girls treated with
      carbamazepine and oxcarbazepine. However, all patients were clinically euthyroid,
      and these changes were reversible after AED withdrawal. Persons with epilepsy
      treated with AEDs are at increased risk for fracture. Not only is this increased
      because of seizure activity, but also because of treatment with AEDs. AED
      treatment results in decreased bone mineral density, the most sensitive predictor
      of fracture and changes in biochemical indices of bone metabolism, including
      calcium, vitamin D, and markers of bone formation and resorption. Identifying
      each of these endocrine abnormalities is important because it may be necessary
      and beneficial to change AED treatment. In addition, multiple therapies exist for
      the treatment of polycystic ovary syndrome, infertility, and decreased bone
      mineral density.

PMID- 15967091
TI  - Pharmacotherapy of Mood Disorders in Epilepsy: The Role of Newer Psychotropic
      Drugs.
AB  - Depression in patients with epilepsy (PWE) is a relatively common comorbidity
      that has a significant negative impact on their quality of life. Therefore,
      recognition and management of a comorbid depressive disorder is paramount to
      achieve successful comprehensive treatment in PWE. Depression in epilepsy may
      mimic primary depressive disorders, but in a significant percentage of depressed
      PWE, the clinical semiology has an atypical presentation and fails to meed any of
      the diagnostic criteria established in the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition. Despite the relatively high prevalence of
      depression in epilepsy and its frequent atypical presentation, there has been
      only one controlled study (in 1979) to establish the safety and efficacy of
      antidepressant drugs in PWE. Accordingly, clinicians must rely on data from
      studies of pharmacotherapy of primary depression. These data are adequate to
      guide the clinician in the basic principles of pharmacotherapy of depression in
      PWE. Many questions are yet to be answered, including: 1) are the expectations of
      symptom remission to pharmacotherapy in PWE different in typical and atypical
      forms of depression, and do they differ from those of patients with primary
      depression? and 2) are the doses of antidepressant drugs necessary to yield
      symptom remission different between PWE and those patients with primary mood
      disorders?

PMID- 15967093
TI  - Oligodendroglioma.
AB  - Surgery, radiotherapy, and chemotherapy are the standard treatment modalities for
      all primary brain tumors. Oligodendroglial tumors are uncommon primary brain
      tumors that typically are classified as low-grade or anaplastic based on their
      histologic appearance. A great deal of controversy has surrounded the diagnosis
      of an oligodendroglioma because no unique immunohistochemical marker exists to
      diagnose this tumor, forcing pathologists to render a diagnosis based on
      subjective microscopic features. Although once considered relatively rare,
      oligodendroglial tumors have been increasing in incidence because pathologists
      have become less rigorous about this diagnosis. However, recent advances in our
      understanding of the molecular genetic changes associated with brain tumors have
      identified loss of heterozygosity of chromosomes 1p and 19q as a unique genetic
      signature of most oligodendroglial tumors, an advance that has paved the way for
      pathologists to use molecular diagnostics to identify these tumors with improved
      reliability. These genetic derangements have significant clinical and therapeutic
      implications because they have been associated with a predictable and durable
      response to treatment, particularly chemotherapy, and an improved prognosis. The
      unique chemosensitivity of oligodendroglial tumors has been recognized by
      neurooncologists for at least 15 years, and various chemotherapeutic agents have
      been used to manage these diseases. However, the appropriate timing of
      chemotherapy, and the drugs of choice remain controversial. Increasingly,
      neurooncologists are reluctant to use radiotherapy as initial management for
      these diseases because of concerns surrounding the late neurocognitive sequelae
      of cranial irradiation. These toxicities are particularly important for patients
      with low-grade oligodendrogliomas in whom the prognosis often exceeds 10 years.
      Consequently, with the accumulating evidence supporting the chemosensitivity of
      low-grade and anaplastic oligodendrogliomas and the recent ability to use
      molecular diagnostics to identify a chemosensitive subset of oligodendrogliomas,
      neurooncologists are increasingly administering chemotherapy as the initial
      intervention for all oligodendroglial tumors that harbor favorable genetic
      derangements. Additionally, although immediate postoperative treatment is
      uniformly administered to patients with anaplastic oligodendrogliomas, there has
      been an increasing tendency to defer definitive therapy for those with low-grade
      oligodendrogliomas until evidence of progression. The development of
      temozolomide, an oral and well-tolerated alkylating agent that has activity
      against oligodendroglial tumors, has accelerated this trend to the extent that
      currently many patients with newly diagnosed low-grade and anaplastic
      oligodendrogliomas are offered this drug as initial treatment. This paper reviews
      the current management of oligodendrogliomas, with an emphasis on the expanding
      role of chemotherapy for these neoplasms.

PMID- 15967092
TI  - The Treatment of Malignant Gliomas.
AB  - The optimal management of patients with malignant gliomas begins with the
      accurate determination of the pathologic diagnosis based on adequate sampling of
      the tumor. Clear differences in prognosis and therapeutic options have been
      established for the various tumor grades and cellular classification. Current
      recommendations, on the basis of the results of a recent phase III randomized
      trial, are that patients with glioblastoma should have maximal surgical resection
      followed by concurrent radiation and chemotherapy with temozolomide. It is
      further recommended that patients then be treated with 6 to 12 months of adjuvant
      temozolomide. However, despite the shown improvement in survival with this
      chemoradiation regimen, the impact on outcome is modest. It is increasingly
      evident that a greater understanding of the molecular mechanisms of gliomagenesis
      is needed to improve treatments for these patients. Recent and ongoing
      investigations strongly indicate that specific molecular markers tremendously
      impact prognosis and often can predict response to treatment. For example,
      allelic loss of the 1p and 19q chromosome arms predicts a dramatic improvement in
      response to treatment and survival for tumors histologically classified as
      anaplastic oligodendroglioma. Future advances for treating primary brain tumors
      likely will be directly related to our ability to molecularly subcategorize
      tumors and customize therapy based on the molecular profile within each
      histologic type and grade of tumor. This is evident in preliminary data
      indicating that inactivation of the methyl guanine methyltransferase gene by
      hypermethylation of the promoter region specifically predicts a better tumor
      response rate to chemotherapies that alkylate DNA as their mechanism of action.
      Similarly, elucidation of overly active signal transduction pathways within tumor
      cells may provide an opportunity to select the optimal therapeutic regimen
      composed of modulators of these pathways, analogous to restricting the use of
      trastuzumab to breast cancers expressing the Her-2 receptor. Advances in treating
      primary malignant brain tumors will likely depend on collaborative clinical
      trials that are designed to select patients on the basis of histologic and
      molecular characteristics and to determine the optimal biologic dose of the best
      agent that can treat each specific tumor type.

PMID- 15967094
TI  - Brain Stem Tumors.
AB  - Brain stem tumors are heterogeneous. They range from the diffuse pontine tumors,
      which are almost invariably fatal despite all known therapies, to lower-grade
      focal or exophytic tumors that often have a very good prognosis with surgery or
      observation only. In this article, we review the epidemiology of brain stem
      tumors and note that diffuse pontine tumors, although rare, are a significant
      contributor to mortality among pediatric oncology patients. Diagnosis in typical
      cases is made using a magnetic resonance imaging scan without biopsy. No highly
      effective standard treatment exists; therefore, inclusion of eligible patients in
      well-designed clinical research studies is extremely important. If an appropriate
      trial is not available, conventionally fractionated external beam radiation
      therapy can provide good short-term palliation to a significant proportion of
      patients. An important area of preclinical research that may soon be investigated
      in clinical trials for patients with diffuse pontine tumors is interstitial
      infusion of therapeutic agents, and the rationale for that approach is described
      in detail. Lastly, autopsy should be considered for patients who die of diffuse
      pontine tumors with the goal of obtaining tumor tissue for biological studies
      that may in the future lead to novel therapies.

PMID- 15967095
TI  - Treatment of Medical Complications in Patients with Brain Tumors.
AB  - Patients with primary brain tumors and those with cerebral metastases are at risk
      throughout their illness for several major medical problems, including vasogenic
      edema, seizures, and symptomatic venous thrombosis. In turn, the corticosteroids,
      anti-epileptic drugs, and anticoagulants used to treat these problems may produce
      significant adverse effects and result in important drug-drug interactions that
      may complicate chemotherapy. Although few Class I studies address any of these
      issues, guidelines can be offered to maximize quality of life and minimize
      hospital readmissions. Optimal management of brain edema involves minimizing
      corticosteroid use and tapering the steroid dose slowly to avoid steroid
      withdrawal symptoms. Prophylaxis of Pneumocystis pneumonia is necessary for
      patients requiring corticosteroids for more than 1 month. Anti-epileptic drugs
      (AEDs) should be avoided unless patients experience seizures. If possible, non
      CTY (P450) enzyme-inducing drugs should be chosen. AED levels should be obtained
      frequently during corticosteroid taper. Multimodality venous thrombosis
      prophylaxis should begin at the time of the original surgery with external leg
      compression and unfractionated subcutaneous heparin or a low molecular weight
      heparin (LMWH). Brain tumor patients with symptomatic venous thrombosis or
      pulmonary embolism can be anticoagulated safely with warfarin or with LMWH, and
      LMWHs are preferable from the standpoints of efficacy, safety, and convenience
      for long-term outpatient treatment of venous thrombosis. Clinicians should be
      aware of potential drug-drug interactions between prescribed AEDs and
      chemotherapy and possible interactions with complementary and alternative
      therapies chosen by their patients. They also should be aware of interventions to
      minimize late sequelae of brain tumors and their treatment, including cognitive
      decline, depression, and increased stroke risk.

PMID- 15967096
TI  - The tyrosine kinase pyk2 promotes migration and invasion of glioma cells.
AB  - Glioblastoma multiforme is extraordinarily aggressive due to the propensity of
      cells to migrate away from the tumor core into the surrounding normal brain. In
      this report, we investigated the role of proline-rich tyrosine kinase 2 (Pyk2)
      and FAK with regard to influencing glioma cell phenotypes. Expression of Pyk2
      stimulated glioma cell migration, whereas expression of FAK inhibited glioma cell
      migration and stimulated cell cycle progression. Pyk2 autophosphorylation was
      necessary, but not sufficient, to stimulate cellular migration. The N-terminal
      domain of Pyk2 is required for stimulation of migration as an N-terminally
      deleted variant of Pyk2 failed to stimulate migration, whereas expression of an
      autonomous Pyk2 N-terminal domain inhibited cell migration. Substitution of the C
      terminal domain of Pyk2 with the corresponding domain of FAK stimulated cell
      migration as effectively as wild-type Pyk2; however, substitution of the N
      terminal domain of Pyk2 with that of FAK inhibited cell migration, substantiating
      that the N-terminal domain of Pyk2 was required to stimulate migration. Silencing
      of Pyk2 expression by RNA interference significantly inhibited glioma migration.
      Cell migration was restored on re-expression of Pyk2, but expression of FAK in
      Pyk2 knockdown cells failed to restore migration. We conclude that Pyk2 plays a
      central role in the migratory behavior of glioblastomas.

PMID- 15967097
TI  - Differential expression of IGF components and insulin receptor isoforms in human
      seminoma versus normal testicular tissue.
AB  - Insulin-like growth factors (IGF) have mitogenic and antiapoptotic functions, and
      may be involved in tumor growth. The purpose of the study was to investigate the
      role of IGF components in seminoma compared to normal testis. Normal testicular
      tissues from autopsy cases and seminoma from surgery cases were obtained for
      microarray and real-time reverse transcription polymerase chain reaction (RT-PCR)
      analysis of IGF-1, IGF-2, IGF receptor type 1 (IGF-R1), IGF-R2, insulin receptor
      isoforms A (IR-A) and B (IR-B), and IGF-binding proteins (IGFBP) 1-6. IGF-2 was
      localized by immunohistochemistry. IGFBP-5 protein expression was evaluated by
      Western blot analysis. mRNA expression in microarray and real-time RT-PCR showed
      similar tendencies: IGF-1, IGF-R1, IGF-R2, IR-A, and IGFBP-2 were not different
      in both groups. IGF-2, IR-B, IGFBP-1, IGFBP-4, and IGFBP-6 mRNA were
      downregulated in seminoma. IGFBP-3 tended to be upregulated in pT1 seminoma, but
      downregulated in pT2 stages. IGFBP-5 and IGF-2 protein expression correlated with
      mRNA expression. In conclusion, downregulation of mainly inhibiting IGFBPs may
      allow a stimulated tumor growth. The downregulated IGF-2 does not seem to be
      involved in the growth regulation of seminoma. Constantly expressed genes (e.g.,
      IGF-1, IGF-R1, IR-A, and IGFBP-2) may reflect an involvement in spermatogenesis,
      but may also play a major role in tumor growth as their expression is not
      downregulated despite the lack of spermatogenesis in tumor tissue.

PMID- 15967098
TI  - Selective suppression of in vivo tumorigenicity by semaphorin SEMA3F in lung
      cancer cells.
AB  - Loss of the 3p21.3-encoded semaphorins, SEMA3B and SEMA3F, is implicated in lung
      cancer development. Although both antagonize VEGF binding/response to neuropilin
      (NRP) receptors, in lung cancer lines, SEMA3F is predominantly expressed and
      preferentially utilizes NRP2. In lung cancer patients, SEMA3F loss correlates
      with advanced disease and increased VEGF binding to tumor cells. In cell lines,
      VEGF enhances adhesion and migration in an integrin-dependent manner, and
      exogenous SEMA3F causes cells to round and lose extracellular contacts. Using
      retroviral infections, we established stable SEMA3F transfectants in two NSCLC
      cell lines, NCI-H157 and NCI-H460. When orthotopically injected into nude rats,
      both control lines caused lethal tumors in all recipients. In contrast, all
      animals receiving H157-SEMA3F cells, survived to 100 days, whereas all H157
      controls succumbed. In H460 cells, which express NRP1 but not NRP2, SEMA3F did
      not prolong survival. This antitumor effect in H157 cells was associated with
      loss of activated alpha(v)beta(3) integrin and adhesion to extracellular matrix
      components. In addition, H157-SEMA3F cells, and parental H157 cells exposed to
      SEMA3F-conditioned medium, showed loss of p42/p44 MAPK phosphorylation. Thus, in
      this in vivo lung cancer model, SEMA3F has potent antitumor effects, which may
      impinge on activated integrin and MAPK signaling.

PMID- 15967099
TI  - Acute tumor response to ZD6126 assessed by intrinsic susceptibility magnetic
      resonance imaging.
AB  - The effective magnetic resonance imaging (MRI) transverse relaxation rate R(2)*
      was investigated as an early acute marker of the response of rat GH3
      prolactinomas to the vascular-targeting agent, ZD6126. Multigradient echo (MGRE)
      MRI was used to quantify R(2)*, which is sensitive to tissue deoxyhemoglobin
      levels. Tumor R(2)* was measured prior to, and either immediately for up to 35
      minutes, or 24 hours following administration of 50 mg/kg ZD6126. Following MRI,
      tumor perfusion was assessed by Hoechst 33342 uptake. Tumor R(2)* significantly
      increased to 116 +/- 4% of baseline 35 minutes after challenge, consistent with
      an ischemic insult induced by vascular collapse. A strong positive correlation
      between baseline R(2)* and the subsequent increase in R(2)* measured 35 minutes
      after treatment was obtained, suggesting that the baseline R(2)* is prognostic
      for the subsequent tumor response to ZD6126. In contrast, a significant decrease
      in tumor R(2)* was found 24 hours after administration of ZD6126. Both the 35
      minute and 24-hour R(2)* responses to ZD6126 were associated with a decrease in
      Hoechst 33342 uptake. Interpretation of the R(2)* response is complex, yet
      changes in tumor R(2)* may provide a convenient and early MRI biomarker for
      detecting the antitumor activity of vascular-targeting agents.

PMID- 15967100
TI  - Dynamic contrast-enhanced and diffusion MRI show rapid and dramatic changes in
      tumor microenvironment in response to inhibition of HIF-1alpha using PX-478.
AB  - PX-478 is a new agent known to inhibit the hypoxia-responsive transcription
      factor, HIF-1alpha, in experimental tumors. The current study was undertaken in
      preparation for clinical trials to determine which noninvasive imaging
      endpoint(s) is sensitive to this drug's actions. Dynamic contrast-enhanced (DCE)
      and diffusion-weighted (DW) magnetic resonance imaging (MRI) were used to monitor
      acute effects on tumor hemodynamics and cellularity, respectively. Mice bearing
      human xenografts were treated either with PX-478 or vehicle, and imaged over
      time. DW imaging was performed at three b values to generate apparent diffusion
      coefficient of water (ADCw) maps. For DCE-MRI, a macromolecular contrast reagent,
      BSA-Gd-DTPA, was used to determine vascular permeability and vascular volume
      fractions. PX-478 induced a dramatic reduction in tumor blood vessel permeability
      within 2 hours after treatment, which returned to baseline by 48 hours. The anti
      VEGF antibody, Avastin, reduced both the permeability and vascular volume. PX-478
      had no effect on the perfusion behavior of a drug-resistant tumor system, A-549.
      Tumor cellularity, estimated from ADCw, was significantly decreased 24 and 36
      hours after treatment. This is the earliest significant response of ADC to
      therapy yet reported. Based on these preclinical findings, both of these imaging
      endpoints will be included in the clinical trial of PX-478.

PMID- 15967101
TI  - The vascular-ablative agent VEGF(121)/rGel inhibits pulmonary metastases of MDA
      MB-231 breast tumors.
AB  - VEGF(121)/rGel, a fusion protein composed of the growth factor VEGF(121) and the
      recombinant toxin gelonin (rGel), targets the tumor neovasculature and exerts
      impressive cytotoxic effects by inhibiting protein synthesis. We evaluated the
      effect of VEGF(121)/rGel on the growth of metastatic MDA-MB-231 tumor cells in
      SCID mice. VEGF(121)/rGel treatment reduced surface lung tumor foci by 58%
      compared to controls (means were 22.4 and 53.3, respectively; P < .05) and the
      mean area of lung colonies by 50% (210 +/- 37 m(2) vs 415 +/- 10 m(2) for
      VEGF(121)/rGel and control, respectively; P < .01). In addition, the vascularity
      of metastatic foci was significantly reduced (198 +/- 37 vs 388 +/- 21
      vessels/mm(2) for treated and control, respectively). Approximately 62% of
      metastatic colonies from the VEGF(121)/rGel-treated group had fewer than 10
      vessels per colony compared to 23% in the control group. The VEGF receptor Flk-1
      was intensely detected on the metastatic vessels in the control but not in the
      VEGF(121)/rGel-treated group. Metastatic foci present in lungs had a three-fold
      lower Ki-67 labeling index compared to control tumors. Thus, the antitumor
      vascular-ablative effect of VEGF(121)/rGel may be utilized not only for treating
      primary tumors but also for inhibiting metastatic spread and vascularization of
      metastases.

PMID- 15967102
TI  - A novel targeted therapy of Leydig and granulosa cell tumors through the
      luteinizing hormone receptor using a hecate-chorionic gonadotropin beta conjugate
      in transgenic mice.
AB  - We investigated the antitumoral efficacy, endocrine consequences, and molecular
      mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin
      (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with
      a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice
      expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T
      antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R)
      expressing Leydig and granulosa cell tumors, and wild-type control littermates
      were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks.
      Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden
      (P < .05), whereas a concomitant increase (testis; P < .05) or no change (ovary)
      in tumor volumes occured with Hectate treatment. A drop in serum progesterone,
      produced by the tumors, and an increase in LH levels occured in Hecate-CGbeta
      treated mice, in comparison with vehicle and Hecate groups, providing further
      support for the positive treatment response. Hecate-CGbeta conjugate induced a
      rapid and cell-specific membrane permeabilization of LHR-expressing cells in
      vitro, suggesting a necrotic mode of cell death without activation of apoptosis.
      These results prove the principle that the Hecate-CGbeta conjugate provides a
      novel specific lead into gonadal somatic cell cancer therapy by targeted
      destruction of LHR-expressing tumor cells.

PMID- 15967103
TI  - A specific inhibitor of TGF-beta receptor kinase, SB-431542, as a potent
      antitumor agent for human cancers.
AB  - Small molecule inhibitors of signaling pathways have proven to be extremely
      useful for the development of therapeutic strategies for human cancers. Blocking
      the tumor-promoting effects of transforming growth factor-beta (TGF-beta) in
      advanced stage carcinogenesis provides a potentially interesting drug target for
      therapeutic intervention. Although very few TGF-beta receptor kinase inhibitors
      (TRKI) are now emerging in preclinical studies, nothing is known about how these
      inhibitors might regulate the tumor-suppressive or tumor-promoting effects of TGF
      beta, or when these inhibitors might be useful for treatment during cancer
      progression. We have investigated the potential of TRKI in new therapeutic
      approaches in preclinical models. Here, we demonstrate that the TRKI, SB-431542,
      inhibits TGF-beta-induced transcription, gene expression, apoptosis, and growth
      suppression. We have observed that SB-431542 attenuates the tumor-promoting
      effects of TGF-beta, including TGF-beta-induced EMT, cell motility, migration and
      invasion, and vascular endothelial growth factor secretion in human cancer cell
      lines. Interestingly, SB-431542 induces anchorage independent growth of cells
      that are growth-inhibited by TGF-beta, whereas it reduces colony formation by
      cells that are growth-promoted by TGF-beta. However, SB-431542 has no effect on a
      cell line that failed to respond to TGF-beta. This represents a novel potential
      application of these inhibitors as therapeutic agents for human cancers with the
      goal of blocking tumor invasion, angiogenesis, and metastasis, when tumors are
      refractory to TGF-beta-induced tumor-suppressor functions but responsive to tumor
      promoting effects of TGF-beta.

PMID- 15967104
TI  - Mechanical entrapment is insufficient and intercellular adhesion is essential for
      metastatic cell arrest in distant organs.
AB  - In this report, we challenge a common perception that tumor embolism is a size
      limited event of mechanical arrest, occurring in the first capillary bed
      encountered by blood-borne metastatic cells. We tested the hypothesis that
      mechanical entrapment alone, in the absence of tumor cell adhesion to blood
      vessel walls, is not sufficient for metastatic cell arrest in target organ
      microvasculature. The in vivo metastatic deposit formation assay was used to
      assess the number and location of fluorescently labeled tumor cells lodged in
      selected organs and tissues following intravenous inoculation. We report that a
      significant fraction of breast and prostate cancer cells escapes arrest in a lung
      capillary bed and lodges successfully in other organs and tissues. Monoclonal
      antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen
      antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-l
      leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell
      adhesive interactions, inhibited by >90% the in vivo formation of breast and
      prostate carcinoma metastatic deposits in mouse lung and bones. Our results
      indicate that metastatic cell arrest in target organ microvessels is not a
      consequence of mechanical trapping, but is supported predominantly by
      intercellular adhesive interactions mediated by cancer-associated Thomsen
      Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3.
      Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell
      lodging in target organs.

PMID- 15967105
TI  - Tumor vessel compression hinders perfusion of ultrasonographic contrast agents.
AB  - Contrast-enhanced ultrasound (CEUS) is an advanced approach to in vivo assessment
      of tumor vascularity and is being increasingly adopted in clinical oncology. It
      is based on 1- to 10 microm-sized gas microbubbles, which can cross the capillary
      beds of the lungs and are effective echo enhancers. It is known that high cell
      density, high transendothelial fluid exchange, and poorly functioning lymphatic
      circulation all provoke solid stress, which compresses vessels and drastically
      reduces tumor blood flow. Given their size, we supposed that the perfusion of
      microbubbles is affected by anatomic features of tumor vessels more than are
      contrast agents traditionally used in dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI). Here, we compared dynamic information obtained from
      CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences
      in vessel anatomy. We found that tumors with small, flattened vessels show a much
      higher resistance to microbubble perfusion than to MRI contrast agents, and
      appear scarcely vascularized at CEUS examination, despite vessel volume adequate
      for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis
      when tumors have small or collapsed vessels, integrated analysis using CEUS and
      DCE-MRI allows in vivo identification of tumors with a vascular profile
      frequently associated with malignant phenotypes.

PMID- 15967107
TI  - Seven novel and stable translocations associated with oncogenic gene expression
      in malignant melanoma.
AB  - Cytogenetics has not only precipitated the discovery of several oncogenes, but
      has also led to the molecular classification of numerous malignancies. The
      correct identification of aberrations in many tumors has, however, been hindered
      by extensive tumor complexity and the limitations of molecular cytogenetic
      techniques. In this study, we have investigated five malignant melanoma (MM) cell
      lines from at least three different passages using high-resolution R-banding and
      the recently developed methods of comparative genomic hybridization and
      multicolor or multiplex fluorescence in situ hybridization. We subsequently
      detected nine consistent translocations, seven of which were novel:
      dic(1;11)(p10;q14), der(9)t(3;9)(p12;p11), der(4)t(9;4;7)(q33:p15-q23:q21),
      der(14)t(5;14)(q12;q32), der(9)t(9;22)(p21;q11), der(19)t(19;20)(p13.3;p11),
      der(10)t(2;12;7;10)(q31:p12-->pter:q11.2-->q31:q21), der(19)t(10;19)(q23;q13),
      and der(20)t(Y;20)(q11.23;q13.3). Furthermore, using the human HG-U133A GeneChip,
      positive expression levels of oncogenes or tumor-related genes located at the
      regions of chromosomal breakpoints were identified, including AKT1, BMI1, CDK6,
      CTNNB1, E2F1, GPNMB, GPRK7, KBRAS2, LDB2, LIMK1, MAPK1, MEL, MP1, MUC18, NRCAM,
      PBX3, RAB22A, RAB38, SNK, and STK4, indicating an association between chromosomal
      breakpoints and altered gene expression. Moreover, we also show that growth of
      all five cell lines can be significantly reduced by downregulating CDK6 gene
      expression with small interfering RNA (siRNA). Because the majority of these
      breakpoints have been reported previously in MM, our results support the idea of
      common mechanisms in this disease.

PMID- 15967106
TI  - Erythropoietin signaling promotes invasiveness of human head and neck squamous
      cell carcinoma.
AB  - Erythropoietin (Epo) is used for managing anemia in cancer patients. However,
      recent studies have raised concerns for this practice. We investigated the
      expression and function of Epo and the erythropoietin receptor (EpoR) in tumor
      biopsies and cell lines from human head and neck cancer. Epo responsiveness of
      the cell lines was assessed by Epoetin-alpha-induced tyrosine phosphorylation of
      the Janus kinase 2 (JAK2) protein kinase. Transmigration assays across Matrigel
      coated filters were used to examine the effects of Epoetin-alpha on cell
      invasiveness. In 32 biopsies, we observed a significant association between
      disease progression and expression of Epo and its receptor, EpoR. Expression was
      highest in malignant cells, particularly within hypoxic and infiltrating tumor
      regions. Although both Epo and EpoR were expressed in human head and neck
      carcinoma cell lines, only EpoR was upregulated by hypoxia. Epoetin-alpha
      treatment induced prominent JAK2 phosphorylation and enhanced cell invasion.
      Inhibition of JAK2 phosphorylation reduced both basal and Epo-induced
      invasiveness. Our findings support a role for autocrine or paracrine Epo
      signaling in the malignant progression and local invasiveness of head and neck
      cancer. This mechanism may also be activated by recombinant Epo therapy and could
      potentially produce detrimental effects in rhEpo-treated cancer patients.

PMID- 15967108
TI  - SAK, a new polo-like kinase, is transcriptionally repressed by p53 and induces
      apoptosis upon RNAi silencing.
AB  - Chip profiling of a p53 temperature-sensitive tumor model identified SAK (Snk/Plk
      akin kinase), encoding a new member of polo-like kinases (PLKs), as a gene
      strongly repressed by wild-type p53. Further characterization revealed that SAK
      expression was downregulated by wild-type p53 in several tumor cell models.
      Computer search of a 1.7-kb SAK promoter sequence revealed three putative p53
      binding sites, but p53 failed to bind to any of these sites, indicating that SAK
      repression by p53 was not through a direct p53 binding to the promoter.
      Transcriptional analysis with luciferase reporters driven by SAK promoter
      deletion fragments identified SP-1 and CREB binding sites, which together
      conferred a two-fold SAK repression by p53. However, the repression was not
      reversed by cotransfection of SP-1 or CREB, suggesting a lack of interference
      between p53 and SP-1 or CREB. Significantly, p53-mediated SAK repression was
      largely reversed in a dose-dependent manner by Trichostatin A, a potent histone
      deacetylase (HDAC) inhibitor, suggesting an involvement of HDAC transcription
      repressors in SAK repression by p53. Biologically, SAK RNA interference (RNAi)
      silencing induced apoptosis, whereas SAK overexpression attenuated p53-induced
      apoptosis. Thus, SAK repression by p53 is likely mediated through the recruitment
      of HDAC repressors, and SAK repression contributes to p53-induced apoptosis.

PMID- 15967109
TI  - Hypoxia-inducible factor-1alpha and the glycolytic phenotype in tumors.
AB  - Metastatic tumors generally exhibit aerobic glycolysis (the Warburg effect). The
      advent of [18F]fluorodeoxyglucose positron emission tomography imaging, coupled
      with recent findings linking hypoxia-inducible factor (HIF-1alpha) overexpression
      to aggressive cancers, has rekindled an interest in this aspect of tumor
      metabolism. These studies explore the role of HIF-1alpha in human breast cancer
      lines and its relationship to glycolytic regulation. Here we demonstrate that,
      under normal oxygen conditions, nonmetastatic cells consume less glucose and
      express low HIF-1alpha, whereas metastatic cells constitutively express high
      glycolysis and HIF-1alpha, suggesting that dysregulation of HIF-1alpha may induce
      the Warburg effect. This hypothesis was tested by renormalizing HIF-1alpha levels
      in renal carcinoma cells, leading to inhibition of aerobic glycolysis.

PMID- 15967110
TI  - Colorectal cancer "methylator phenotype": fact or artifact?
AB  - It has been proposed that human colorectal tumors can be classified into two
      groups: one in which methylation is rare, and another with methylation of several
      loci associated with a "CpG island methylated phenotype (CIMP)," characterized by
      preferential proximal location in the colon, but otherwise poorly defined. There
      is considerable overlap between this putative methylator phenotype and the well
      known mutator phenotype associated with microsatellite instability (MSI). We have
      examined hypermethylation of the promoter region of five genes (DAPK, MGMT,
      hMLH1, p16INK4a, and p14ARF) in 106 primary colorectal cancers. A graph depicting
      the frequency of methylated loci in the series of tumors showed a continuous,
      monotonically decreasing distribution quite different from the previously claimed
      discontinuity. We observed a significant association between the presence of
      three or more methylated loci and the proximal location of the tumors. However,
      if we remove from analysis the tumors with hMLH1 methylation or those with MSI,
      the significance vanishes, suggesting that the association between multiple
      methylations and proximal location was indirect due to the correlation with MSI.
      Thus, our data do not support the independent existence of the so-called
      methylator phenotype and suggest that it rather may represent a statistical
      artifact caused by confounding of associations.

PMID- 15967111
TI  - A role for K-ras in conferring resistance to the MEK inhibitor, CI-1040.
AB  - PD184352/CI-1040 is a potent and selective MEK1/2 inhibitor that represents the
      first MEK-targeted agent to enter clinical trials. Here, we report the
      development and molecular characterization of CI-1040 resistance in the murine
      colon 26 (C26) carcinoma cell line. The growth rate of the resistant line (C26/CI
      1040r) in the presence of 2 microM CI-1040 is comparable to that of parental C26
      cells in the absence of CI-1040. C26/CI-1040r cells are approximately 100-fold
      more resistant than the parental line to CI-1040 inhibition in soft agar and are
      less sensitive to the induction of apoptosis that normally occurs in response to
      CI-1040 treatment. K-ras expression is significantly elevated in C26/CI-1040r
      cells. We confirmed a causative role for K-ras in conferring resistance to CI
      1040 by transfecting K-ras into parental C26 cells, whereupon an elevation in the
      levels of phosphorylated ERK1/2 was observed in addition to resistance to CI
      1040. Furthermore, an in vivo-derived MEK inhibitor-resistant line also shows
      increased K-ras expression. Our data suggest that increasing activated K-ras
      expression represents one potential mechanism by which tumor cells that initially
      are responsive to blockade of the MAP kinase pathway can overcome their
      sensitivity to MEK inhibition.

PMID- 15967112
TI  - WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human
      hepatocellular carcinoma and involved in cell proliferation.
AB  - In an attempt to disclose mechanisms of hepatocarcinogenesis and discover novel
      target molecules for the diagnosis and treatment of hepatocellular carcinomas
      (HCCs), we previously analyzed expression profiles of HCC tissues by means of
      human cDNA microarray. Among the genes upregulated in tumor tissues compared with
      their nontumor counterparts, we focused on a novel gene, termed WDRPUH, and
      characterized its biologic function. WDRPUH encodes a predicted 620-amino acid
      protein containing 11 highly conserved WD40-repeat domains. Multiple-tissue
      Northern blot analysis revealed its specific expression in the testis among 16
      normal tissues examined. Transfection of plasmids designed to express WDRPUH
      specific siRNA significantly reduced its expression in HCC cells and resulted in
      growth suppression of transfected cells. Interestingly, we found that WDRPUH
      associated with HSP70, proteins of the chaperonin-containing TCP-1 (CCT1)
      complex, as well as BRCA2. These findings have disclosed a novel insight into
      hepatocarcinogenesis and suggested that WDRPUH may be a molecular target for the
      development of new strategies to treat HCCs.

PMID- 15967113
TI  - mTOR promotes survival and astrocytic characteristics induced by Pten/AKT
      signaling in glioblastoma.
AB  - Combined activation of Ras and AKT leads to the formation of astrocytic
      glioblastoma multiforme (GBM) in mice. In human GBMs, AKT is not mutated but is
      activated in approximately 70% of these tumors, in association with loss of PTEN
      and/or activation of receptor tyrosine kinases. Mechanistic justification for the
      therapeutic blockade of targets downstream of AKT, such as mTOR, in these cancers
      requires demonstration that the oncogenic effect of PTEN loss is through elevated
      AKT activity. We demonstrate here that loss of Pten is similar to AKT activation
      in the context of glioma formation in mice. We further delineate the role of mTOR
      activity downstream of AKT in the maintenance of AKT+KRas-induced GBMs. Blockade
      of mTOR results in regional apoptosis in these tumors and conversion in the
      character of surviving tumor cells from astrocytoma to oligodendroglioma. These
      data suggest that mTOR activity is required for the survival of some cells within
      these GBMs, and mTOR appears required for the maintenance of astrocytic character
      in the surviving cells. Furthermore, our study provides the first example of
      conversion between two distinct tumor types usually thought of as belonging to
      specific lineages, and provides evidence for signal transduction-mediated
      transdifferentiation between glioma subtypes.

PMID- 15967114
TI  - [18F]FDG uptake and PCNA, Glut-1, and Hexokinase-II expressions in cancers and
      inflammatory lesions of the lung.
AB  - PURPOSE: The aim of this study was to evaluate the relationships among
      [18F]fluorodeoxyglucose ([18F]-FDG) uptake, Glut-1 and HK-II expressions, and
      grade of inflammation in resected lung lesions. MATERIALS AND METHODS: Sixty
      patients had undergone preoperative 18F-FDG-PET imaging and thoracotomy. For
      semiquantitative analysis of 18F-FDG uptake, partial volume effect corrected
      maximum standardized uptake values (pSUVs) were calculated. Immunohistochemical
      staining was performed in resected specimens using anti-Glut-1, anti-HK-II, and
      anti-proliferative cellular nuclear antigen (PCNA) antibodies, and
      immunoreactivities were scored as G-, H-, and P-indexes on a five-point scale (0:
      0%; 1: 20%, 2: 40%; 3: 60%; 4: 80%, and 5: 100% percentages of strongly
      immunoreactive cells).Grade of inflammation was also evaluated. RESULTS: The
      malignant lesions had higher pSUV and higher G- and H- than nonmalignant lesions.
      pSUVs correlated with the G- (p < .001), H- (p < .01), and P-indexes (p < .01) in
      malignant lesions. In adenocarcinomas, cancers with lower differentiation showed
      higher expression of Glut-1 and HK-II than those with higher differentiation. A
      positive linear regression was observed between pSUVs and the grading of
      inflammation in nonmalignant lesions (p < .05). CONCLUSIONS: Our study indicates
      that 18F-FDG uptake in lung cancer correlates well with the Glut-1, HK-II, and
      PCNA expression. For nonmalignant lesions, the presence of a higher inflammatory
      process correlated with 18F-FDG uptake.

PMID- 15967115
TI  - Membrane type 1 matrix metalloprotease cleaves laminin-10 and promotes prostate
      cancer cell migration.
AB  - Disruption of the extracellular matrix by proteases is crucial for tumor
      invasion. Laminin-10 (Ln-10) has previously been identified as a substrate for
      cell migration and cell adhesion, and is present in the basal lamina (BL) of both
      normal prostate and prostate cancer. Here, we investigate a role for membrane
      type 1 matrix metalloprotease (MT1-MMP) in modifying this Ln-10-rich BL. MT1-MMP
      is a transmembrane member of the MMP family that has been demonstrated to be
      upregulated as prostate cancer progresses from normal to prostate intraepithelial
      neoplasia to invasive cancer, suggesting a role for MT1-MMP in the invasion of
      prostate cancer. We show that MT1-MMP cleaves the alpha5 chain of purified human
      Ln-10 from its 350-kDa form into 310-, 190-, 160-, and 45-kDa fragments. This
      cleavage causes a decrease in DU-145 prostate cancer cell adhesion to purified Ln
      10, and an increase in transmigration of DU-145 cells through cleaved Ln-10. We
      also show that prostate cancer cells expressing membrane-bound MT1-MMP cleave the
      alpha5 chain of Ln-10. Ln alpha5-chain cleavage is also observed in human
      prostate cancer tissues. These findings suggest that prostate cancer cells
      expressing high levels of MT1-MMP have increased invasive potential through their
      ability to degrade and invade Ln-10 barriers.

PMID- 15967116
TI  - Eosinophil granulocytes account for indoleamine 2,3-dioxygenase-mediated immune
      escape in human non-small cell lung cancer.
AB  - Indoleamine 2,3-dioxygenase (IDO), a catabolizing enzyme of tryptophan, is
      supposed to play a role in tumor immune escape. Its expression in solid tumors
      has not yet been well elucidated: IDO can be expressed by the tumor cells
      themselves, or by ill-defined infiltrating cells, possibly depending on tumor
      type. We have investigated IDO expression in 25 cases of non-small cell lung
      cancer (NSCLC). Using histochemistry and immunohistochemistry, we found that IDO
      was expressed not by tumor cells, but by normal cells infiltrating the
      peritumoral stroma. These cells were neither macrophages nor dendritic cells, and
      were identified as eosinophil granulocytes. The amount of IDO-positive
      eosinophils varied in different cases, ranging from a few cells to more than 50
      per field at x200 magnification. IDO protein in NSCLC was enzymatically active.
      Therefore, at least in NSCLC cases displaying a large amount of these cells in
      the inflammatory infiltrate, IDO-positive eosinophils could exert an effective
      immunosuppressive action. On analyzing the 17 patients with adequate follow-up, a
      significant relationship was found between the amount of IDO-positive infiltrate
      and overall survival. This finding suggests that the degree of IDO-positive
      infiltrate could be a prognostic marker in NSCLC.

PMID- 15967117
TI  - The characteristics of astrocytomas and oligodendrogliomas are caused by two
      distinct and interchangeable signaling formats.
AB  - Chronic platelet-derived growth factor (PDGF) signaling in glial progenitors
      leads to the formation of oligodendrogliomas in mice, whereas chronic combined
      Ras and Akt signaling leads to astrocytomas. Different histologies of these
      tumors imply that the pathways activated by these two oncogenic stimulations are
      different, and that the apparent lineage of the tumor cells may result from
      specific signaling activity. Therefore, we have investigated the signaling
      effects of PDGF in culture and in gliomas in vivo. In culture, PDGF transiently
      activates ERK1/2 and Akt, and subsequently elevates p21 and PCNA expression
      similar to chronic PDGF autocrine signaling in cultured astrocytes and PDGF
      induced oligodendrogliomas in vivo. Culture experiments show that autocrine PDGF
      stimulation, and combined active Ras and Akt generate signaling patterns that are
      in some ways mutually exclusive. Furthermore, forced Akt activity in the context
      of chronic PDGF stimulation results in cells with an astrocytic differentiation
      pattern both in culture and in vivo. These data imply that these two
      interconvertible signaling motifs are distinct in mice and lead to gliomas
      resembling the two major glioma histologies found in humans. The ability of
      signaling activity to convert tumor cells from one lineage to another presents a
      mechanism for the development of tumors apparently comprised of cells from
      multiple lineages.

PMID- 15967118
TI  - Altered expression of TFF-1 and CES-2 in Barrett's Esophagus and associated
      adenocarcinomas.
AB  - Identification of biomarkers to recognize individuals with Barrett's esophagus
      (BE) predisposed to develop malignancy is currently a pressing issue. We utilized
      gene expression profiling to compare molecular signatures of normal esophagus and
      stomach, BE, and adenocarcinoma (AC) to identify such potential biomarkers. Over
      22,000 genes were analyzed by oligonucleotide microarrays on 38 unique RNA
      Unsupervised and supervised clusterings were performed on a subset of 2849 genes
      that varied most significantly across the specimens. Immunohistochemistry (IHC)
      for two of the significantly differentially expressed gene products was performed
      on tissue microarrays. Unsupervised clustering identified two discernable
      molecular BE profiles, one of which was similar to normal gastric tissue ("BE1"),
      and another that was shared by several of the AC specimens ("BE2"). The BE1
      profile included expression of several genes that have been described as tumor
      suppressor genes, most notably trefoil factor 1 (TFF-1). The BE2 profile included
      expression of genes previously found overexpressed in cancers, such as
      carboxylesterase-2 (CES-2). IHC demonstrated the loss of TFF-1 late in the
      progression of BE to AC. It also revealed CES-2 as being upregulated in AC
      documented to have arisen in the presence of BE. These potential biomarkers, as
      well as the relative expression of genes from BE1 versus those from BE2, may be
      validated in the future to aid in risk stratification and guide treatment
      protocols in patients with BE and associated AC.

PMID- 15967119
TI  - LY293111 improves efficacy of gemcitabine therapy on pancreatic cancer in a
      fluorescent orthotopic model in athymic mice.
AB  - Pancreatic cancer has an abysmal prognosis because of late diagnosis and lack of
      effective therapeutics. New drugs are desperately needed. The present study
      determined the effect of the LTB4 receptor antagonist, LY293111, on tumor growth
      and metastases in a fluorescent orthotopic model of pancreatic cancer. Pancreatic
      cancer cells (S2-013) with stable expression of enhanced green fluorescent
      protein were implanted into the duodenal pancreatic lobe of athymic mice. Animals
      were allocated to four groups (eight mice per group): control (no treatment);
      LY293111; gemcitabine; and LY293111 + gemcitabine. Monitoring of the surgical
      procedure and follow-up examinations at 2, 3, and 4 weeks after implantation to
      monitor tumor growth and metastases were performed using a fluorescence
      microscope and the reversible skin-flap technique. A staging and scoring system
      was developed to evaluate tumor progression, based on the TNM classification.
      Control animals developed end-stage disease with invasive cancer, metastases, and
      cachexia. Tumor growth and incidence of metastases were significantly reduced in
      all treated mice. However, combined treatment with LY293111 and gemcitabine was
      most effective. LY293111 is a novel therapeutic agent for pancreatic cancer,
      which improves the efficacy of gemcitabine. It is well tolerated and can be
      administered orally and, therefore, provides a new hope for patients suffering
      from pancreatic adenocarcinoma.

PMID- 15967120
TI  - Gastrin-releasing peptide receptor mediates activation of the epidermal growth
      factor receptor in lung cancer cells.
AB  - Gastrin-releasing peptide receptor (GRPR) and the epidermal growth factor
      receptor (EGFR) are expressed in several cancers including non-small cell lung
      cancer (NSCLC). Here we demonstrate the activation of EGFR by the GRPR ligand,
      gastrin-releasing peptide (GRP), in NSCLC cells. GRP induced rapid activation of
      p44/42 MAPK in lung cancer cells through EGFR. GRP-mediated activation of MAPK in
      NSCLC cells was abrogated by pretreatment with the anti-EGFR-neutralizing
      antibody, C225. Pretreatment of NSCLC cells with neutralizing antibodies to the
      EGFR ligands, TGF-A or HB-EGF, also decreased GRP-mediated MAPK activation. On
      matrix metalloproteinase (MMP) inhibition, GRP failed to activate MAPK in NSCLC
      cells. EGF and GRP both stimulated NSCLC proliferation, and inhibition of either
      EGFR or GRPR resulted in cell death. Combining a GRPR antagonist with the EGFR
      tyrosine kinase inhibitor, gefitinib, resulted in additive cytotoxic effects.
      Additive effects were seen at gefitinib concentrations from 1 to 18 microM,
      encompassing the ID50 values of both gefitinib-sensitive and gefitinib-resistant
      NSCLC cell lines. Because a major effect of GRPR appears to be promoting the
      release of EGFR ligand, this study suggests that a greater inhibition of cell
      proliferation may occur by abrogating EGFR ligand release in consort with
      inhibition of EGFR.

PMID- 15967121
TI  - Methotrexate-induced accumulation of fluorescent annexin V in collagen-induced
      arthritis.
AB  - We examined the accumulation of Cy5.5-labeled annexin V in the paws of mice with
      and without collagen-induced arthritis, with and without methotrexate (MTX)
      treatment, by near-infrared fluorescence imaging. Fluorescence reflectance
      imaging (FRI) of paws was performed 48 hr after MTX injection and at 10 min and 3
      hr after the injection of Cy5.5-annexin V (1 nmol dye per mouse). With arthritic
      paws, MTX treatment caused a 7-fold increase in fluorescence intensity compared
      with the paws of untreated mice and a 4-fold increase compared to nonarthritic
      paws of MTX-treated mice (p < .001 each). Tissue samples of paws were examined
      histologically for Cy5.5 fluorescence and by TUNEL staining for apoptosis. Cy5.5
      annexin V was seen in the hyperplastic synovia of MTX-treated mice, and TUNEL
      staining for apoptosis showed apoptotic cells in the hyperplastic synovia.
      Monitoring the uptake of Cy5.5-annexin V in arthritic paws by FRI provided a
      method of assessing a response to MTX, a response that was readily quantitated
      with simple instrumentation and that occurred before conventional measurements of
      treatment response.

PMID- 15967122
TI  - Visualization through magnetic resonance imaging of DNA internalized following
      "in vivo" electroporation.
AB  - The ability to visualize plasmid DNA entrapment in muscle cells undergoing an "in
      vivo" electroporation treatment was investigated on BALB/c mice using a 7-T
      magnetic resonance imaging (MRI) scanner using the paramagnetic Gd-DOTA-spd
      complex as imaging reporter. Gd-DOTA-spd bears a tripositively charged spermidine
      residue that yields a strong binding affinity toward the negatively charged DNA
      chain (6.4 kb, K(a) = 2.2 x 10(3) M(-1) for approximately 2500 +/- 500 binding
      sites). Cellular colocalization of Gd-DOTA-spd and plasmid DNA has been validated
      by histological analysis of excised treated muscle. In vivo MRI visualization of
      Gd-DOTA-spd distribution provides an excellent route to access the cellular
      entrapment of plasmid DNA upon applying an electroporation pulse.

PMID- 15967123
TI  - A potential Dubin-Johnson syndrome imaging agent: synthesis, biodistribution, and
      microPET imaging.
AB  - Dubin-Johnson syndrome (DJS) is caused by a deficiency of the human canalicular
      multispecific organic anion transporter (cMOAT). A new lipophilic copper-64
      complex of 1,4,7-tris(carboxymethyl)-10-(tetradecyl)-1,4,7,10-tetraazadodecane
      (5) was prepared and evaluated for potential as a diagnostic tool for DJS. The
      prepared ligand was labeled with (64)Cu citrate in high radiochemical purity. In
      vivo uptake and clearance of the complex was determined through biodistribution
      studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR(-)) rats.
      In normal rats, the radioactive copper complex was cleared quickly from the body
      exclusively through the hepatic pathway. The (64)Cu complex was taken up rapidly
      by the liver and quickly excreted into the small intestine and then the upper
      large intestine, whereas <1% ID/organ was found in the kidney at all time points
      post injection. Whereas activity was accumulated continuously in the liver of TR(
      ) rats, it was not excreted into the small intestine. MicroPET studies of normal
      and TR(-) rats were consistent with biodistribution data and showed dramatically
      different images. This study strongly suggests that cMOAT is involved in
      excretion of (64)Cu-5. The significant difference between the biodistribution
      data and microPET images of the normal and TR(-) rats demonstrates that this new
      (64)Cu complex may allow noninvasive diagnosis of DJS in humans.

PMID- 15967124
TI  - Imaging multidrug resistance P-glycoprotein transport function using microPET
      with technetium-94m-sestamibi.
AB  - The best characterized mechanism of multidrug resistance (MDR) in cancer involves
      the MDR1 efflux transporter P-glycoprotein (Pgp). The positron-emitting
      radiotracer hexakis(2-methoxyisobutylisonitrile)-(94m)Tc ((94m)Tc-MIBI) was
      synthesized and validated in cell transport studies as a substrate for MDR1 Pgp.
      In vivo small-scale PET imaging and biodistribution studies of mdr1a/1b (-/-)
      gene deleted and wild-type mice demonstrated the use of (94m)Tc-MIBI to detect
      Pgp function. The reversal effect of a Pgp modulator was shown in tissue
      distribution studies of KB 3-1 (Pgp-) and KB 8-5 (Pgp+) tumor-bearing nude mice.
      The current (94m)Tc-MIBI experiments parallel previous studies employing (99m)Tc
      MIBI, showing essentially identical performance of the two technetium
      radiotracers and providing biological validation of (94m)Tc-MIBI for PET imaging
      of multidrug resistance.

PMID- 15967125
TI  - 3-d image analysis of fluorescent drug binding.
AB  - Fluorescent ligands provide the means of studying receptors in whole tissues
      using confocal laser scanning microscopy and have advantages over antibody- or
      non-fluorescence-based method. Confocal microscopy provides large volumes of
      images to be measured. Histogram analysis of 3-D image volumes is proposed as a
      method of graphically displaying large amounts of volumetric image data to be
      quickly analyzed and compared. The fluorescent ligand BODIFY FL-prazosin (QAPB)
      was used in mouse aorta. Histogram analysis reports the amount of ligand-receptor
      binding under different conditions and the technique is sensitive enough to
      detect changes in receptor availability after antagonist incubation or generic
      manipulations. QAPB binding was concentration dependent, causing concentration
      related rightward shifts in histogram. In the presence of 10 microM
      phenoxybenzamine (blocking agent), the QAPB (50 nM) histogram overlaps the
      autofluorescence curve. The histogram obtained for the 1D knockout aorta lay to
      the left of that control and 1B knockout aorta, indicating a reduction in 1D
      receptors. We have shown, for the first time, that it is possible to graphically
      display binding of a fluorescent drug to a biological tissue. Although our
      application is specific to adrenergic receptors, the general method could be
      applied to any volumetric, fluorescence-image-based assay.

PMID- 15967126
TI  - Cellular imaging of inflammation after experimental spinal cord injury.
AB  - The ability to visualize the cellular inflammatory responses after experimental
      spinal cord injury (SCI) was investigated using a clinical 1.5-T magnetic
      resonance imaging scanner, a custom-built, high-strength gradient coil insert, a
      3-D fast imaging employing steady-state acquisition (FIESTA) imaging sequence and
      a superparamagnetic iron oxide (SPIO) contrast agent. An "active labeling"
      approach was used, with SPIO administered intravenously at different time points
      following SCI. Our results show that this strategy can be used to visualize
      clusters of iron-labeled cells associated with the inflammatory response in SCI.
      Of particular importance for this application was the finding that in FIESTA
      images hemorrhage does not cause signal loss. In T2-weighted spin echo or T2*
      weighted gradient-echo images, which are more commonly used to detect signal loss
      associated with SPIO, the signal loss associated with hemorrhage interferes with
      the detection of iron-induced signal loss. FIESTA, therefore, allowed us to
      discriminate between iron associated with blood products in hemorrhage that
      occurs in acute SCI and the iron associated with SPIO-labeled cells accumulating
      in the injured cord.

PMID- 15967128
TI  - Detection of dysplastic intestinal adenomas using a fluorescent folate imaging
      probe.
AB  - Macrophages have long been recognized as a prominent component of tumors.
      Activated macrophages overexpress folate receptors and we used this phenomenon to
      image inflammatory reactions in colon dysplasia using a fluorescent folate probe
      (FFP). APC(Delta468) mice injected with FFP showed fluorescent adenomas (target
      to-background ratio, adenoma vs. adjacent normal mucosa, of 2.46 +/- 0.41),
      significantly higher (p < .001) than adenomas in animals injected with a non
      folate-containing control probe. Fluorescence-activated cell-sorting analysis
      revealed a 3-fold higher content of Mac1-positive cells in colonic adenomas
      compared with normal adjacent mucosa (6.8% vs. 2.2%), and confirmed the source of
      FFP-positive cells to be primarily an F4/80-positive macrophage subpopulation.
      Taken together, these results indicate that probe potentially can be used to
      image dysplastic intestinal adenomas in vivo.

PMID- 15967127
TI  - An interventional magnetic resonance imaging technique for the molecular
      characterization of intraprostatic dynamic contrast enhancement.
AB  - The biological characterization of an individual patient's tumor by noninvasive
      imaging will have an important role in cancer care and clinical research if the
      molecular processes that underlie the image data are known. Spatial heterogeneity
      in the dynamics of magnetic resonance imaging contrast enhancement (DCE-MRI) is
      hypothesized to reflect variations in tumor angiogenesis. Here we demonstrate the
      feasibility of precisely colocalizing DCE-MRI data with the genomic and proteomic
      profiles of underlying biopsy tissue using a novel MRI-guided biopsy technique in
      a patients with prostate cancer.

PMID- 15967129
TI  - History, homicide, and the healing hand.

PMID- 15967130
TI  - Punishment or treatment? Inebriety, drink, and drugs, 1860-2004.

PMID- 15967131
TI  - Nazi medicine and research on human beings.

PMID- 15967132
TI  - Forensic medicine: past, present, and future.

PMID- 15967133
TI  - Forensic genetics.

PMID- 15967134
TI  - The neurobiology of aggression.

PMID- 15967135
TI  - Profiling the criminal mind: does it actually work?

PMID- 15967136
TI  - Global child trafficking.

PMID- 15967137
TI  - Bride burning.

PMID- 15967138
TI  - Dispatch from the (un)civil memory wars.

PMID- 15967139
TI  - Screening for domestic violence--bridging the evidence gaps.

PMID- 15967140
TI  - Doctor-assisted dying: what difference does legalisation make?

PMID- 15967141
TI  - The doctor's role in bioterrorism.

PMID- 15967142
TI  - The black market in prescription drugs.

PMID- 15967143
TI  - Use of organs from executed Chinese prisoners.

PMID- 15967144
TI  - Carandiru.

PMID- 15967145
TI  - Medical care of prisoners in the USA.

PMID- 15967146
TI  - The Steve Biko affair.

PMID- 15967147
TI  - Murder most medical, disposal most discreet.

PMID- 15967148
TI  - Medicine in the UK after Shipman: has "all changed, changed utterly"?

PMID- 15967149
TI  - Beyond organ retention: the new human tissue bill.

PMID- 15967150
TI  - Bodily theft past and present: a tale of two sermons.

PMID- 15967151
TI  - Crime, confidentiality, and clinical judgment.

PMID- 15967152
TI  - Medicine and the law.

PMID- 15967153
TI  - Sexually violent predator laws: psychiatry in service to a morally dubious
      enterprise.

PMID- 15967154
TI  - Over my dead body.

PMID- 15967155
TI  - "The answers are always in the body": forensic pathology in US crime programmes.

PMID- 15967156
TI  - Sick detectives.

PMID- 15967157
TI  - An important contribution to the literature.

PMID- 15967158
TI  - Cytokines, PGE2 and endotoxic fever: a re-assessment.
AB  - The innate immune system serves as the first line of host defense against the
      deleterious effects of invading infectious pathogens. Fever is the hallmark among
      the defense mechanisms evoked by the entry into the body of such pathogens. The
      conventional view of the steps that lead to fever production is that they begin
      with the biosynthesis of pyrogenic cytokines by mononuclear phagocytes stimulated
      by the pathogens, their release into the circulation and transport to the
      thermoregulatory center in the preoptic area (POA) of the anterior hypothalamus,
      and their induction there of cyclooxygenase (COX)-2-dependent prostaglandin
      (PG)E(2), the putative final mediator of the febrile response. But data
      accumulated over the past 5 years have gradually challenged this classical
      concept, due mostly to the temporal incompatibility of the newer findings with
      this concatenation of events. Thus, the former studies generally overlooked that
      the production of cytokines and the transduction of their pyrogenic signals into
      fever-mediating PGE(2) proceed at relatively slow rates, significantly slower
      certainly than the onset latency of fever produced by the i.v. injection of
      bacterial endotoxic lipopolysaccharides (LPS). Here, we review the conflicts
      between the earlier and the more recent findings and summarize new data that
      reconcile many of the contradictions. A unified model based on these data
      explicating the generation and maintenance of the febrile response is presented.
      It postulates that the steps in the production of LPS fever occur in the
      following sequence: the immediate activation by LPS of the complement (C)
      cascade, the stimulation by the anaphylatoxic C component C5a of Kupffer cells,
      their consequent, virtually instantaneous release of PGE(2), its excitation of
      hepatic vagal afferents, their transmission of the induced signals to the POA via
      the ventral noradrenergic bundle, and the activation by the thus, locally
      released norepinephrine (NE) of neural alpha(1)- and glial alpha(2)
      adrenoceptors. The activation of the first causes an immediate, PGE(2)
      independent rise in core temperature (T(c)) [the early phase of fever; an
      antioxidant-sensitive PGE(2) rise, however, accompanies this first phase], and of
      the second a delayed, PGE(2)-dependent T(c) rise [the late phase of fever].
      Meanwhile-generated pyrogenic cytokines and their consequent upregulation of
      blood-brain barrier cells COX-2 also contribute to the latter rise. The
      consecutive steps that initiate the febrile response to LPS would now appear,
      therefore, to occur in an order different than conceived originally.

PMID- 15967159
TI  - Enhanced 15-HPETE production during oxidant stress induces apoptosis of
      endothelial cells.
AB  - Oxidant stress plays an important role in the etiology of vascular diseases by
      increasing rates of endothelial cell apoptosis, but few data exist on the
      mechanisms involved. Using a unique model of oxidative stress based on selenium
      deficiency (-Se), the effects of altered eicosanoid production on bovine aortic
      endothelial cells (BAEC) apoptosis was evaluated. Oxidant stress significantly
      increased the immediate oxygenation product of arachidonic acid metabolized by
      the 15-lipoxygenase pathway, 15-hydroxyperoxyeicosatetraenoic acid (15-HPETE).
      Treatment of -Se BAEC with TNFalpha/cyclohexamide (CHX) exhibited elevated levels
      of apoptosis, which was significantly reduced by the addition of a specific 15
      lipoxygenase inhibitor PD146176. Furthermore, the addition of 15-HPETE to
      PD146176-treated BAEC, partially restored TNF/CHX-induced apoptosis. Increased
      exposure to 15-HPETE induced apoptosis, as determined by internucleosomal DNA
      fragmentation, chromatin condensation, caspase-3 activation, and caspase-9
      activation, which suggests mitochondrial dysfunction. The expression of Bcl-2
      protein also was decreased in -Se BAEC. Addition of a caspase-9 inhibitor (LEHD
      fmk) completely blocked 15-HPETE-induced chromatin condensation in -Se BAEC,
      suggesting that 15-HPETE-induced apoptosis is caspase-9 dependent. Increased
      apoptosis of BAEC as a result of oxidant stress and subsequent production of 15
      HPETE may play a critical role in a variety of inflammatory based diseases.

PMID- 15967160
TI  - Influence of ovarian steroid hormones or platelet-activating factor on mRNA of
      platelet-activating factor receptor in endometrial explant perfusion cultures
      from ovariectomized bovine.
AB  - Platelet-activating factor (PAF) and its receptors are involved in inflammatory
      like processes of the uterus associated with increased vascular permeability. PAF
      is supposed to be influenced by ovarian steroid hormones. The present study was
      undertaken to examine whether progesterone (P(4)), estradiol (E(2)) or PAF
      influence the PAF receptor gene expression in perfused endometrial explants
      derived from ovariectomized bovine. Furthermore, we identified the cell types in
      which the PAF receptor gene and protein are expressed. In endometrial explants,
      applications of 10 nM P(4) or 10nM P(4) plus 10 nM E(2) for 24 h induced elevated
      transcript levels of PAF receptor in comparison to the controls or after
      treatment with 1 nM E(2). When explants were administered 10 nM E(2), a slight
      decrease in the transcript level was recorded. After treatment of explants with
      PAF, no significant changes in PAF receptor mRNA expression was observed compared
      to the control group. We demonstrate that PAF receptor immunoreactivity and mRNA
      are detected mainly in the luminal epithelium, epithelial cells of the
      superficial glands and to a lesser degree in stroma. Levels of PAF receptor mRNA
      in bovine endometrial explants were correlated with PAF receptor protein
      localization assessed by immunohistochemistry. The regulation of PAF receptor by
      progesterone in bovine endometrial explants suggests that PAF is involved in the
      physiological process of reproduction.

PMID- 15967161
TI  - Regulation of vascular endothelial cell growth factor expression in mouse mammary
      tumor cells by the EP2 subtype of the prostaglandin E2 receptor.
AB  - Prostaglandin E(2) (PGE(2)), a major metabolite of the cyclooxygenase pathway in
      the mammary gland, induces angiogenesis during mammary tumor progression. To
      better define the molecular mechanisms involved, we examined the role of the G
      protein-coupled receptors (GPCR) for PGE(2) in mammary tumor cell lines isolated
      from MMTV-cyclooxygenase-2 (COX-2) transgenic mice. Expression of the EP2 subtype
      of the PGE(2) receptor was correlated with the tumorigenic phenotype and the
      ability to induce vascular endothelial growth factor (VEGF). Overexpression of
      EP2 by adenoviral transduction into EP2-null cells resulted in the induction of
      VEGF expression in response to PGE(2) and CAY10399, an EP2 receptor agonist. The
      induction of VEGF by the EP2 receptor did not require the hypoxia inducible
      factor (HIF)-1alpha pathway, MAP kinase pathway, or phosphoinositide-3-kinase/Akt
      pathway, but required the cAMP/protein kinase A pathway. These results suggest
      that EP2 receptor is a critical element for PGE(2) mediated VEGF induction in
      mouse mammary tumor cells.

PMID- 15967162
TI  - Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse
      the inhibition of prostacyclin generation by aortas in streptozotocin diabetic
      rats.
AB  - The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma
      lipids, oxidative stress and the ability of aortic tissues to generate
      prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats,
      plasma total cholesterol, triglycerides and serum glucose significantly increased
      compared to nondiabetic rats. Atorvastatin administration to diabetic rats did
      not affect hyperglycemia but significantly reduced plasma total cholesterol and
      triglycerides compared to diabetic rats. The oxidative stress markers urinary
      isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma
      protein carbonyl content significantly increased in diabetic rats compared to
      nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly
      reduced oxidative stress levels compared to diabetic rats, but urinary
      isoprostane and liver TBARS remained significantly higher than nondiabetic rats.
      Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in
      diabetic rats compared to nondiabetic rats. Atorvastatin administration to
      diabetic rats did not reverse that inhibition. These results were discussed in
      the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase
      and cyclooxygenase-2 activities and the genetic difference between rats and other
      mammals regarding the level of vascular superoxide dismutase (SOD) activity.

PMID- 15967163
TI  - Different edible oil beneficial effects (canola oil, fish oil, palm oil, olive
      oil, and soybean oil) on spontaneously hypertensive rat glomerular enlargement
      and glomeruli number.
AB  - We have tested the different edible oil effects on the blood pressure (BP)
      control and the following glomerular protection. Six groups of 12-week-old male
      spontaneously hypertensive rats (SHR) (n = 5), have received different edible
      oils (fish, canola, palm, olive, and soybean) or a placebo by gavage for 13
      weeks. Renal cortex was analyzed through light microscopy and stereology. Usual
      BP increase, glomerulosclerosis, glomerular enlargement, and glomeruli loss in
      SHR has been prevented (fish, canola and palm oils) or attenuated (olive and
      soybean oils) by these oil long-term administration. The most favorable effect
      has been seen in the fish oil administration (source of n-3 polyunsaturated fatty
      acids, PUFA, eicosapentaenoic and docosahexaenoic acids), followed by both canola
      and palm oils (source of n-3 PUFA plus n-9 monounsaturated, MUFA, and saturated
      fatty acid, respectively), and finally both olive and soybean oils (source of n-9
      MUFA and n-6 PUFA, respectively).

PMID- 15967164
TI  - COX-2 inhibitors and genetic background reduce mammary tumorigenesis in
      cyclooxygenase-2 transgenic mice.
AB  - Cyclooxygenase-2 (COX-2) overexpression is a widely recognized feature of human
      breast cancer and inhibitors of the enzyme have antitumor effects in a subset of
      tumor settings. Previously, we demonstrated that direct overexpression of COX-2
      under control of the mammary-specific MMTV promoter/enhancer, was itself
      oncogenic and lead to the induction of mammary tumors in multiparous, outbred CD1
      mice. In the present study, we provide evidence that COX-2 dependent tumor
      progression can also be studied in FVB/N, an inbred strain widely used for
      analysis of breast cancer progression. In these mice, the human COX-2 transgene
      was strongly induced during pregnancy/lactation and mammary tumors developed
      after multiple pregnancies. However, crossing the COX-2 FVB/N mice with the
      C57BL6 strain resulted in loss of the mammary tumorigenic phenotype despite the
      fact that the human COX-2 gene was induced. Treatment of the COX-2 transgenic
      mice in the FVB/N strain with celecoxib (1600 ppm), a COX-2 selective inhibitor,
      resulted significant reduction in tumor size and multiplicity when compared to
      transgenic mice fed with control chow. SC-560 (20 ppm), a COX-1 selective
      inhibitor did not have significant effect on tumorigenesis. These studies suggest
      that FVB/N is a susceptible mouse strain well suited to the study of COX-2
      mediated tumor progression and may provide a tool for the identification of
      interacting genes and therapeutic treatments for this clinically important
      target.

PMID- 15967165
TI  - Role of guanine nucleotide exchange factor P-Rex-2b in sphingosine 1-phosphate
      induced Rac1 activation and cell migration in endothelial cells.
AB  - Endothelial cell (EC) migration has an important role in angiogenesis.
      Sphingosine-1 phosphate (S1P) stimulates EC migration via activation of Gi
      proteins. In this study, we characterized a mouse guanine nucleotide exchange
      factor (GEF) P-Rex2b for its regulation by Gbetagamma and PI3K and its role in
      S1P-induced Rac1 activation and cell migration in ECs. We found that co
      expression of Gbetagamma or an active form of PI3K (PI3K(AC)) with P-Rex2b
      increased the SRE. Luciferase (SRE.L) reporter gene activity that can be
      stimulated by the Rho family of small GTPases including Rac1. Co-expression with
      P-Rex2b of Gbetagamma and PI3K(AC) or wild type PI3Kgamma that can be activated
      by Gbetagamma led to further increases in the reporter gene activity. Together
      with the finding that co-expression of Gbetagamma and/or PI3K(AC) increased the
      levels of active Rac1, we conclude that P-Rex2b is a Rac GEF that can be
      regulated by Gbetagamma and PI3K. Additionally, we demonstrated that Gbetagamma
      interacted with P-Rex2b, probably through P-Rex2b sequences at the PH domain and
      that the DEP and PDZ domains of P-Rex2b exerted an inhibitory effect on P-Rex2b's
      activity because their deletion increased the SER.L reporter gene activity.
      Furthermore, we found that P-Rex2b is involved in S1P-induced Rac1 activation and
      cell migration in ECs because siRNA-mediated suppression of P-Rex2b expression in
      ECs-diminished Rac1 activation and cell migration in response to S1P. Therefore,
      P-Rex2b is a physiologically significant Rac1 GEF that has an important role in
      the regulation of EC migration.

PMID- 15967166
TI  - Non-genomic effect of steroids on oxytocin-stimulated intracellular mobilization
      of calcium and on prostaglandin F2alpha and E2 secretion from bovine endometrial
      cells.
AB  - Progesterone (P4) was found to interfere directly with the interaction of
      oxytocin (OT) with its own receptor in bovine endometrium. The aim of these
      studies was to investigate whether other steroids have a similar effect.
      Endometrial slices and epithelial endometrial cells from days 14 to 18 of the
      estrous cycle were used. Progesterone (P4), pregnenolone (P5), 17beta
      hydroxyprogesterone (17-OHP4), the P4 receptor antagonist (aP4), and testosterone
      (T4) did not affect (P > 0.01) basal secretion of PGE2 and PGF 2alpha during 4h
      of incubation but all steroids inhibited (P < 0.05) OT-stimulated PGF2alpha
      secretion both from endometrial slices and from dispersed cells. None of the
      steroids used affected OT-stimulated PGE2 secretion from the cells (P > 0.01). In
      the next experiment it was studied whether P5, 17-OHP4 and P4 pretreatment for
      30min modifies intracellular mobilization of Ca(2+) in response to OT. Oxytocin
      induced a rapid increase in intracellular Ca(2+)concentrations within 15s, while
      cells pretreated with steroids this increase occurred later. The total amount of
      intracellular Ca(2+)concentrations was lower (P < 0.05) in cells preincubated
      with steroids compared to controls. We conclude that steroids and aP4 are able to
      suppress OT-stimulated endometrial PGE2 and PGF2alpha secretion via a non-genomic
      pathway.

PMID- 15967167
TI  - The effect of prostaglandin E1 on ion currents of NG108-15 cells.
AB  - The aim of this study was to elucidate the mechanism by which prostaglandin E(1)
      (PGE(1)) acts on ion currents of whole-cell voltage-clamped NG108-15
      neuroblastomaxglioma hybrid cells. Ruptured and perforated patch were used. The
      holding current at -70 mV, the current-voltage curve produced by ramp pulses from
      -70 to 0 mV and the T-type and hva (high-voltage-activated) Ca(2+) currents
      associated with rectangular pulses were recorded. Bath application of PGE(1) (0.2
      or 3 microM) reversibly increased the holding current, an effect mimicked by the
      prostanoid agonist iloprost (5-50 nM). The PGE(1) effect was totally blocked by
      the cAMP-antagonist Rp-cAMPS whereas H-89, an inhibitor of protein kinase A
      (PKA), failed to inhibit it, even when applied in the fairly high bath
      concentration of 30 microM. PGE(1) and iloprost also inhibited the T-type and hva
      Ca(2+) currents and this effect of PGE(1) was likewise not prevented by H-89. In
      some of the cells, the PGE(1) effect on holding current could be mimicked by 8
      pCPT-2Me-cAMP (100-300 microM), a selective agonist of Epac (exchange protein
      activated by cAMP), but unlike the PGE(1) effect its action was not abolished by
      Rp-cAMPS. The effect of PGE(1) on the the holding current and on the T-type
      Ca(2+) current was diminished when EGTA in the pipette solution was replaced by
      BAPTA, suggesting that Ca(2+) ions are involved in the PGE(1) effect. It is
      concluded that the PGE(1) effect is mediated by cAMP and Ca(2+) ions but not by
      PKA or Epac.

PMID- 15967168
TI  - Pharmacological characterization of guinea pig chemoattractant receptor
      homologous molecule expressed on Th2 cells (CRTH2).
AB  - Chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), a G
      protein-coupled receptor activated by prostaglandin D(2) (PGD(2)), has been
      identified as a receptor expressed on cell types critical to the pathogenesis of
      asthma. The cDNA encoding guinea pig CRTH2 was cloned and mRNA expression
      examined in selected tissues. Transcript profiling of guinea pig CRTH2 indicated
      relatively high levels of expression in bone marrow, intermediate levels in brain
      and relatively low levels in lung, spleen, thymus, lymph node, etc.
      Characterization of the molecular pharmacology of guinea pig CRTH2 revealed that
      guinea pig CRTH2 exhibited a greater affinity for Delta(12)-PGJ(2), a stable
      PGD(2) metabolite relative to human CRTH2. The CRTH2 selective agonists 13,14
      dihydro-15-keto PGD(2) and Delta(12)-PGJ(2) induced the recruitment of
      eosinophils following intradermal administration of these ligands in guinea pigs.
      Chemotaxis of guinea pig eosinophils was elicited by either PGD(2) or Delta(12)
      PGJ(2), and was abolished by a CRTH2-specific antagonist. These results indicate
      that PGD(2) and the stable metabolite, Delta(12)-PGJ(2), play important roles in
      CRTH2 activation in the guinea pig.

PMID- 15967169
TI  - Ruminative coping and post-event processing in social anxiety.
AB  - Cognitive models of social anxiety implicate various factors in the initiation
      and maintenance of socially anxious states, including anticipatory processing,
      self-focused attention and post-event processing. The present study focused on
      post-event processing, which is a post-mortem analysis following a social event
      that is described as ruminative in nature and serves to maintain social anxiety.
      Participants (N=112; 64 women, 48 men) were presented with vignettes that
      involved making mistakes in public and were instructed to record their thoughts
      to allow for the examination of the content of post-event processing. Ruminative
      coping and distraction were assessed via self-report. Results indicated that
      participants high in social anxiety (n=55) were more likely to ruminate and less
      likely to distract when faced with socially anxious stressors compared to those
      low in social anxiety (n=57). Further, as hypothesized, participants high in
      social anxiety recorded more negative thoughts and more upward counterfactual
      thoughts ('if only' type thoughts on how things could have been better;
      associated with negative affect) compared to those low in social anxiety. These
      results are discussed in terms of cognitive models of social anxiety.

PMID- 15967170
TI  - Attempts to control unwanted thoughts in the night: development of the thought
      control questionnaire-insomnia revised (TCQI-R).
AB  - The attempted control of intrusive, uncontrollable thoughts has been implicated
      in the maintenance of a range of psychological disorders. The current paper
      describes the refinement of the Thought Control Questionnaire Insomnia (TCQI;
      Behav. Cogn. Psychoth. 29 (2001)) through its administration to a sample (n=385)
      including good sleepers and individuals with insomnia. Several items with poor
      psychometric properties were discarded, resulting in a 35-item revised TCQI.
      Factor analysis revealed six factors; aggressive suppression, cognitive
      distraction, reappraisal, social avoidance, behavioural distraction, and worry.
      The attempted management of unwanted thoughts was compared across individuals
      with insomnia and good sleepers, and the impact of these strategies on sleep
      quality, anxiety and depression was investigated. With the exception of cognitive
      distraction, individuals with insomnia, relative to good sleepers, more
      frequently used every thought control strategy. The strategies of aggressive
      suppression and worry, in particular, appeared to be unhelpful, with the use of
      these strategies predicting sleep impairment, anxiety and depression. The
      strategy of cognitive distraction appeared to be helpful, with the use of this
      strategy predicting better sleep quality.

PMID- 15967171
TI  - A comparison of autogenous/reactive obsessions and worry in a nonclinical
      population: a test of the continuum hypothesis.
AB  - Employing the autogenous-reactive model of obsessions (Behaviour Research and
      Therapy 41 (2003) 11-29), this study sought to test a hypothesized continuum
      where reactive obsessions fall in between autogenous obsessions and worry with
      respect to several thought characteristics concerning content appraisal,
      perceived form, and thought triggers. Nonclinical undergraduate students (n=435)
      were administered an online packet of questionnaires designed to examine the
      three different types of thoughts. Main data analyses included only those
      displaying moderate levels of obsessions or worries (n=252). According to the
      most distressing thought, three different groups were formed and compared:
      autogenous obsession (n=34), reactive obsession (n=76), and worry (n=142).
      Results revealed that (a) relative to worry, autogenous obsessions were perceived
      as more bizarre, more unacceptable, more unrealistic, and less likely to occur;
      (b) autogenous obsessions were more likely to take the form of impulses, urges,
      or images, whereas worry was more likely to take the form of doubts,
      apprehensions, or thoughts; and (c) worry was more characterized by awareness and
      identifiability of thought triggers, with reactive obsessions through these
      comparisons falling in between. Moreover, reactive obsessions, relative to
      autogenous obsessions, were more strongly associated with both severity of worry
      and use of worrying as a thought control strategy. Our data suggest that the
      reactive subtype represents more worry-like obsessions compared to the autogenous
      subtype.

PMID- 15967172
TI  - Respiratory symptoms and panic in the National Comorbidity Survey: a test of
      Klein's suffocation false alarm theory.
AB  - According to suffocation false alarm theory (Arch. Gen. Psychiatry 50 (1993) 31),
      respiratory symptoms are the symptoms that best distinguish the panic attacks of
      individuals with panic disorder (PD) from those of individuals without PD. Using
      National Comorbidity Survey data from those 609 respondents who had lifetime
      histories of panic attacks or PD, we tested this prediction. Neither respiratory
      symptom (smothering; dyspnea) strongly differentiated between respondents with PD
      and those with only panic attacks. Respiratory symptom endorsement was unrelated
      to PD when the number of other symptoms endorsed was controlled; furthermore,
      respiratory symptoms had slight effect sizes and were not included in a
      multivariate context. In contrast, fear of dying had the largest effect size, an
      association with PD that persisted after control for other symptom endorsement,
      and a continuing importance in multivariate analyses. Strikingly, panic attack
      respondents who reported having had only one panic attack were as likely as PD
      respondents to report respiratory symptoms during panic. These findings, although
      based on retrospective self-report and thus subject to recall bias, are
      inconsistent with the hypothesis that respiratory symptoms during panic have
      diagnostic significance.

PMID- 15967173
TI  - Psychiatric correlates of childhood shyness in a nationally representative
      sample.
AB  - Relations between adult anxiety and mood disorders and retrospective reports of
      excessive childhood shyness were investigated in the US National Comorbidity,
      Survey (n=5877). Results indicated that 26% of women and 19% of men described
      themselves as 'very shy' when they were growing up. Of these shy individuals, 53%
      of women and 40% of men met criteria for a lifetime diagnosis of one or more
      anxiety or mood disorders. Relations between excessive shyness and each of the
      anxiety and mood disorders were examined after adjusting for elevated
      neuroticism, self-criticism, and low maternal care. The largest odds ratios were
      found for social phobia in both men and women, particularly for the complex
      subtype of this disorder. Significant associations also emerged for posttraumatic
      stress disorder in women and for major depressive disorder in men. Childhood
      shyness remained significantly associated with a lifetime history of social
      phobia when individuals with current (past year) social phobia were excluded from
      the analysis. The results of this study suggest that childhood shyness is
      strongly related to the complex subtype of social phobia in the general
      population. Excessive shyness does not appear to be strongly associated with
      other anxiety and mood disorders when related psychosocial and developmental
      dimensions are statistically controlled. Finally, many individuals who report
      excessive childhood shyness do not meet criteria for any anxiety or mood
      disorder. In a similar fashion, approximately 50% of individuals with a lifetime
      history of complex social phobia did not view themselves as very shy when growing
      up.

PMID- 15967174
TI  - Memory and interpretation of visual representations of threat in socially anxious
      and nonanxious individuals.
AB  - The present study was designed to replicate and extend results reported by
      Brendle and Wenzel (Behav. Res. Ther. 42 (2004) 155), who found that socially
      anxious individuals accurately recalled threat-relevant information but
      subsequently imposed a biased interpretation upon that same material, using more
      ecologically valid stimuli. Socially anxious (n=37) and nonanxious (n=47)
      individuals viewed two positive, two negative, and two neutral video vignettes
      and completed two cognitive tasks assessing memory and interpretation of factual
      details immediately and after 48 h. Similar to the results reported by Brendle
      and Wenzel (2004), socially anxious and nonanxious individuals did not differ in
      their memory for details that had been presented in the vignettes. However,
      socially anxious individuals made more negative interpretations of details
      included in the vignettes than nonanxious individuals, although unlike Brendle
      and Wenzel (2004), they did not demonstrate the tendency to make less positive
      interpretations. It is concluded that socially anxious individuals are
      characterized by interpretation biases when presented with threat-relevant
      information, and there is no evidence to suggest that they are characterized by
      memory biases for threat-relevant information.

PMID- 15967175
TI  - Interpretation biases in angry and anxious individuals.
AB  - Although previous research has demonstrated many similarities between anxious and
      angry individuals, few studies have compared the degree and direction to which
      they exhibit cognitive biases in the presence of threat. The present study was a
      preliminary investigation of 28 angry participants, 30 anxious participants, and
      26 non-angry/non-anxious participants who rated the likelihood of various
      explanations to account for ambiguous but potentially threatening events
      described in short prose passages. Angry participants rated the likelihood of
      positive explanations for ambiguous events lower than non-angry/non-anxious
      participants. Angry participants rated the likelihood of anger-related
      explanations higher than anxious and non-angry/non-anxious participants, and both
      angry and anxious participants rated anxiety-related explanations as being more
      likely than non-angry/non-anxious participants. Thus, both angry and anxious
      participants demonstrated a negative interpretation bias, although the bias was
      more pervasive in angry participants.

PMID- 15967176
TI  - The reluctance to generalize corrective experiences in chronic low back pain
      patients: a questionnaire study of dysfunctional cognitions.
AB  - The present study investigated whether pain catastrophizing and pain-related fear
      is related to a reluctance to generalize an experience of lesser pain than
      expected to other similar situations. Eighty-five patients with chronic low back
      pain (40 males; 45 females; age range=21-63 years) completed a series of
      vignettes assessing catastrophizing, overgeneralization, personalization and
      selective abstraction related to general life experiences and to low back pain
      (LBP) experiences. Three vignettes also assessed the lack of generalization of
      corrective experiences related to LBP. Our results showed that dysfunctional
      cognitions related to general life experiences were the strongest predictor of
      the self-denigration subscale of the Beck Depression Inventory (BDI), whereas
      only dysfunctional cognitions related to LBP had a unique contribution in the
      prediction of the somatic and physical function subscale of the BDI. Furthermore,
      dysfunctional cognitions related to LBP were significantly correlated with
      interference with daily life due to pain. As predicted, pain catastrophizing and
      pain-related fear had a unique contribution in predicting the lack of
      generalization of corrective experiences, over and above sociodemogaphic
      variables, pain severity and pain duration.

PMID- 15967177
TI  - The structure of disgust: domain specificity in relation to contamination
      ideation and excessive washing.
AB  - The primary goal of the present study was to employ confirmatory factor analysis
      to compare two theoretical models regarding the factor structure of disgust
      (N=307). The two-factor model of Animal Reminder and Core disgust proposed by
      Rozin et al. (2000) demonstrated superior model fit over a one-factor model that
      has been implicated in prior research. However, contrary to theoretical
      predictions, categorizing Hygiene disgust as Core disgust rather than Animal
      Reminder disgust provided an overall better fit for the two-factor model. The
      second aim of the study was to investigate the relationship between the
      empirically derived two-factor model and contamination ideation and excessive
      washing using structural equation modeling. Findings indicated that the
      Contamination Ideation and Excessive Washing latent factor was specifically
      related to Core disgust (domain specific) and negatively related to Animal
      Reminder disgust. The relevance of these findings in the context of future
      research investigating the role of disgust in specific anxiety disorders is
      discussed.

PMID- 15967178
TI  - Autobiographical memory in angry and anxious individuals.
AB  - Recent studies have found that angry individuals are characterized by more
      pronounced attentional and interpretation biases toward threat than anxious
      individuals. The present study examined anger-related, anxiety-related, and
      neutral autobiographical memories in 35 angry participants, 33 anxious
      participants, and 29 non-angry/non-anxious, or healthy participants. Objective
      indices of autobiographical memories (i.e., retrieval latency, coding of
      specificity and affective tone) suggested that groups retrieved memories with
      similar properties. However, both angry and anxious participants rated their
      memories as less pleasant than healthy participants. These results indicate that
      memory biases are not part of the cognitive sequelae associated with anger and
      anxiety, although aspects of the appraisal of these personal memories are
      distorted.

PMID- 15967179
TI  - Repetitive abrupt structural changes in polyanionic gels: a comparison with
      analogous processes in nerve fibers.
AB  - Repetitive abrupt structural changes can be produced in a small piece of cross
      linked polyacrylate hydrogel by exchanging the divalent counter-ions in the
      superficial gel layer to monovalent cations. The temporal variations of the
      hydrostatic pressure, electric impedance and potential associated with these
      structural changes frequently show striking resemblance to those encountered
      during repetitive excitation of living nerve fibers. Common anions, such as
      fluoride, phosphate, aspartate, chloride, etc., produce a marked lyotropic
      (Hofmeister) effect on the repetitive structural changes both in synthetic
      polyanionic gels and in squid giant nerve fibers. Mechanical stress which brings
      about constraints in the polymer chains is found to facilitate the production of
      repetitive structural changes in the gel. In the stretched superficial layer of a
      synthetic polyanionic gel, a calcium-salt produces highly refractive bundles of
      polymer chains. In the Appendix, a crude model of ionized polymer chains that
      facilitates the consideration of cooperative structural changes in the gel is
      described.

PMID- 15967180
TI  - Rock-scissors-paper game in a chaotic flow: the effect of dispersion on the
      cyclic competition of microorganisms.
AB  - Laboratory experiments and numerical simulations have shown that the outcome of
      cyclic competition is significantly affected by the spatial distribution of the
      competitors. Short-range interaction and limited dispersion allows for
      coexistence of competing species that cannot coexist in a well-mixed environment.
      In order to elucidate the mechanisms that destroy species diversity we study the
      intermediate situation of imperfect mixing, typical in aquatic media, in a model
      of cyclic competition between toxin producing, sensitive and resistant
      phenotypes. It is found, that chaotic mixing, by changing the character of the
      spatial distribution, induces coherent oscillations in the populations. The
      magnitude of the oscillations increases with the strength of mixing, leading to
      the extinction of some species beyond a critical mixing rate. When mixing is non
      uniform in space, coexistence can be sustained at much stronger mixing by the
      formation of partially isolated regions, that prevent global extinction. The
      heterogeneity of mixing may enable toxin producing and sensitive strains to
      coexist for very long time at strong mixing.

PMID- 15967181
TI  - Computation and analysis of time-dependent sensitivities in Generalized Mass
      Action systems.
AB  - Understanding biochemical system dynamics is becoming increasingly important for
      insights into the functioning of organisms and for biotechnological
      manipulations, and additional techniques and methods are needed to facilitate
      investigations of dynamical properties of systems. Extensions to the method of
      Ingalls and Sauro, addressing time-dependent sensitivity analysis, provide a new
      tool for executing such investigations. We present here the results of sample
      analyses using time-dependent sensitivities for three model systems taken from
      the literature, namely an anaerobic fermentation pathway in yeast, a negative
      feedback oscillator modeling cell-cycle phenomena, and the Mitogen Activated
      Protein (MAP) kinase cascade. The power of time-dependent sensitivities is
      particularly evident in the case of the MAPK cascade. In this example it is
      possible to identify the emergence of a concentration of MAPKK that provides the
      best response with respect to rapid and efficient activation of the cascade,
      while over- and under-expression of MAPKK relative to this concentration have
      qualitatively different effects on the transient response of the cascade. Also of
      interest is the quite general observation that phase-plane representations of
      sensitivities in oscillating systems provide insights into the manner with which
      perturbations in the envelope of the oscillation result from small changes in
      initial concentrations of components of the oscillator. In addition to these
      applied analyses, we present an algorithm for the efficient computation of time
      dependent sensitivities for Generalized Mass Action (GMA) systems, the most
      general of the canonical system representations of Biochemical Systems Theory
      (BST). The algorithm is shown to be comparable to, or better than, other methods
      of solution, as exemplified with three biochemical systems taken from the
      literature.

PMID- 15967182
TI  - Post-transplantation dynamics of the immune response to chronic myelogenous
      leukemia.
AB  - We model the immune dynamics between T cells and cancer cells in leukemia
      patients after bone marrow transplants, using a system of six delay differential
      equations to track the various cell-populations. Our approach incorporates time
      delays and accounts for the progression of cells through different modes of
      behavior. We explore possible mechanisms behind a successful cure, whether
      mediated by a blood-restricted immune response or a cancer-specific graft-versus
      leukemia (GVL) effect. Characteristic features of this model include sustained
      proliferation of T cells after initial stimulation, saturated T cell
      proliferation rate, and the possible elimination of cancer cells, independent of
      fixed-point stability. In addition, we use numerical simulations to examine the
      effects of varying initial cell concentrations on the likelihood of a successful
      transplant. Among the observed trends, we note that higher initial concentrations
      of donor-derived, anti-host T cells slightly favor the chance of success, while
      higher initial concentrations of general host blood cells more significantly
      favor the chance of success. These observations lead to the hypothesis that anti
      host T cells benefit from stimulation by general host blood cells, which induce
      them to proliferate to sufficient levels to eliminate cancer.

PMID- 15967183
TI  - Metabolic setpoint control mechanisms in different physiological systems at rest
      and during exercise.
AB  - Using a number of different homeostatic control mechanisms in the brain and
      peripheral physiological systems, metabolic activity is continuously regulated at
      rest and during exercise to prevent catastrophic system failure. Essential for
      the function of these regulatory processes are baseline "setpoint" levels of
      metabolic function, which can be used to calculate the level of response required
      for the maintenance of system homeostasis after system perturbation, and to which
      the perturbed metabolic activity levels are returned to at the end of the
      regulatory process. How these setpoint levels of all the different metabolic
      variables in the different peripheral physiological systems are created and
      maintained, and why they are similar in different individuals, has not been well
      explained. In this article, putative system regulators of metabolic setpoint
      levels are described. These include that: (i) innate setpoint values are stored
      in a certain region of the central nervous system, such as the hypothalamus; (ii)
      setpoint values are created and maintained as a response to continuous external
      perturbations, such as gravity or "zeitgebers", (iii) setpoint values are created
      and maintained by complex system dynamical activity in the different peripheral
      systems, where setpoint levels are regulated by the ongoing feedback control
      activity between different peripheral variables; (iv) human anatomical and
      biomechanical constraints contribute to the creation and maintenance of metabolic
      setpoints values; or (v) a combination of all these four different mechanisms
      occurs. Exercise training and disease processes can affect these metabolic
      setpoint values, but the setpoint values are returned to pre-training or pre
      disease levels if the training stimulus is removed or if the disease process is
      cured. Further work is required to determine what the ultimate system regulator
      of metabolic setpoint values is, why some setpoint values are more stringently
      protected by homeostatic regulatory mechanisms than others, and the role of
      conscious decision making processes in determining the regulation of metabolic
      setpoint values.

PMID- 15967184
TI  - Deconstructing the design of a biological material.
AB  - By identifying the functional conflicts in its design, the cuticle of arthropods
      can be shown to cope with IR and UV irradiation in the same manner as our
      technology-by controlling spectral properties (transmission and reflection).
      However, the skeletal properties of cuticle are integrated with demands for
      sensory transmission, movement, etc, by controlling the local properties of the
      material rather than by changing global parameters (which would be the technical
      solution). On the basis of this study, the biomimetic similarity of cuticle with
      technology is only about 20%, suggesting that we can learn from the design of
      arthropod cuticle.

PMID- 15967185
TI  - Lattice geometry, gap formation and scale invariance in forests.
AB  - The geometry of the lattice used in ecological modeling is important because of
      the local nature of ecological interactions. The latter can generate complex
      behavior such as criticality (scale-invariance). In this work, we implement two
      slightly different forest disturbance models on three lattices, each with square,
      triangular and hexagonal symmetry, in order to study the effect of geometry. We
      calculate the density distribution of gaps in a forest and find bumps in the
      distribution at sizes that depend on lattice geometry. Similar bumps were
      observed in real data but remained unexplainable. We suggest that these bumps
      provide information about the geometry and scale of ecological interactions. We
      also found an effect of geometry on the conditions under which criticality
      appears in model forests. These conditions appear to be more biologically
      realistic, and also linked to the likelihood of local disturbance propagation.
      The scaling exponent of the gap-size distribution, however, was found to be
      independent of both model and geometry, a hallmark of universality.

PMID- 15967186
TI  - Involvement of cellular death signals in the reactivation of herpes simplex virus
      type 1 and lambda bacteriophage from a latent state.
AB  - Herpes simplex virus (HSV) 1 has adapted to the human host through two modes of
      infection, the acute-transient infection that may cause diseases (such as
      encephalitis) and the latent state, which is a source for recurrent infection and
      disease. While much information has been gathered on the cellular and molecular
      concomitants of establishment and maintenance of HSV-1 latent state, the
      biological basis of viral reactivation is still unclear. Despite their obvious
      differences, HSV-1 and the bacterial temperate virus, the bacteriophage lambda,
      shares four distinct features that may help understand the viral latency
      phenomenon: (i) two modes of life cycle and a decision point to choose either
      latency (HSV-1) and lysogeny (bacteriophage lambda), or active replication, that
      results in cell destruction, (ii) establishment of lysogeny/latency of the
      respective virus is associated with protection from cell death, (iii)
      immunity/resistance to super-infection, (iv) agents that trigger mammalian and
      bacterial cell death also induce reactivation of both HSV-1 and lambda
      bacteriophage. Thus, despite their differences, these two viruses might display
      analogous mechanism(s) of reactivation. Based on clinical and experimental data,
      we propose in this hypothesis that while HSV-1 latency, like bacteriophage lambda
      lysogeny, is associated with protection from cell death and restriction to super
      infection, viral reactivation from the latent state is triggered by exogenous
      stress signals that interfere with cellular viability and may eventually lead to
      cell death.

PMID- 15967187
TI  - The evolution of the human mind and logic--mathematics structures.
AB  - The evolution of the human mind is discussed based on: (i) the fact that living
      beings interchange matter, energy and information with their environment, (ii) an
      ontological interpretation of the "reality" of the quantum world, of which logic
      mathematics structures are considered constitutive parts, (iii) recent theories
      according to which living beings are considered as dynamic complex systems
      organized by information, and (iv) the fact that the evolution of living beings
      is guided by information about the environment and by intrinsic information on
      living systems (auto-organization). Assuming the evolution of vision as a model
      we observe that the driving forces that directed the evolution of the eyes, as
      dynamic complex systems, are the information about the environment supplied by
      sunlight and the intrinsic information-gaining mechanism of living organisms.
      Thus, there exists a convergence toward a visual system with the greatest ability
      to obtain light information, like the human eye, and also a divergence that leads
      to the development of specific qualities in some species. As in the case of
      vision the evolution of the human mind-brain cannot be a consequence of factors
      unrelated to the object of its own functioning. The human mind was structured for
      the acquisition from reality of the logic-mathematics structures that underlie
      the whole universe and consequently of an internal representation of the external
      world and of its own self. Thus, these structures are, together with the
      intrinsic capacity for auto-organization of the human brain, the predominant
      driving force of the human mind evolution. Both factors are complementary.

PMID- 15967188
TI  - The reinfection threshold.
AB  - Thresholds in transmission are responsible for critical changes in infectious
      disease epidemiology. The epidemic threshold indicates whether infection invades
      a totally susceptible population. The reinfection threshold indicates whether
      self-sustained transmission occurs in a population that has developed a degree of
      partial immunity to the pathogen (by previous infection or vaccination). In
      models that combine susceptible and partially immune individuals, the reinfection
      threshold is technically not a bifurcation of equilibria as correctly pointed out
      by Breban and Blower. However, we show that a branch of equilibria to a
      reinfection submodel bifurcates from the disease-free equilibrium as transmission
      crosses this threshold. Consequently, the full model indicates that levels of
      infection increase by two orders of magnitude and the effect of mass vaccination
      becomes negligible as transmission increases across the reinfection threshold.

PMID- 15967189
TI  - Current concepts in the etiology and treatment of Behcet disease.
AB  - Behcet disease is an idiopathic, multisystem, chronic, and recurrent disease
      characterized by exacerbations alternating with phases of quiescence, episodic
      panuveitis, and aggressive non-granulomatous occlusive vasculitis of the arteries
      and veins of any size with explosive ocular inflammatory attacks that primarily
      affect the retinal and anterior segment vasculature of the eye. The disease is
      characterized by endothelial dysfunction and may produce a wide variety of
      symptoms. In mild cases, orogenital ulcers and skin lesions are the only findings
      during the entire clinical course, whereas ocular lesions that occur in more than
      half of the cases, frequently bilateral, can eventually lead to blindness.
      Pulmonary, gastrointestinal, and central nervous system involvements may
      sometimes be life-threatening. This review examines the epidemiology, frequency,
      immunology, and immunohistopathology of Behcet disease with recent theories of
      several agents, including phosphoantigens, superantigens, heat-shock proteins,
      and adenosine deaminase. Perspectives on the possible roles of new
      etiopathological molecules, such as nitric oxide, endothelin, and homocysteine,
      are presented. Ocular and systemic clinical features, diagnostic criteria,
      classifications, laboratory, fundus fluorescein angiography, and radiologic
      imaging are discussed. Differential diagnosis, disease in pregnancy and
      childhood, and prognosis with regard to Behcet-induced systemic and ocular
      complications are also evaluated. Traditional and current treatments with
      topical, paraocular and systemic corticosteroids, colchicine, dapsone,
      cyclosporine, azathioprine, methotrexate, cyclophosphamide and chlorambucil are
      summarized and recent insights into the pharmacology and effects of thalidomide,
      tacrolimus (FK-506), interferon-alpha, anti-TNF-alpha blocking monoclonal
      autoantibody (infliximab) and soluble TNF receptor (etanercept) are reviewed. Key
      clinical investigations with the status of ongoing clinical trials aimed at
      addressing the drug's efficacy, surgical care, and studies that have raised the
      possibility of new therapeutic uses are also presented. The challenges posed by
      the drug's teratogenicity and adverse effects are also considered, if present.

PMID- 15967190
TI  - Scleritis.
AB  - Scleritis is typically a severe painful inflammatory process centered in the
      sclera that may involve the cornea, adjacent episclera, and underlying uvea; it
      poses a significant threat to vision. Careful clinical history taking, detailed
      ocular examination, appropriate investigation for ocular disease with or without
      underlying systemic disease, and timely intervention with the use of
      immunosuppressant drugs when necessary, has improved the long-term outcome for
      patients with this disease.

PMID- 15967191
TI  - Acute anterior uveitis and HLA-B27.
AB  - Acute anterior uveitis is the most common form of uveitis. HLA-B27-associated
      acute anterior uveitis is a distinct clinical entity that has wide-ranging
      medical significance due to its ocular, systemic, immunologic, and genetic
      features. The association between HLA-B27 and the spectrum of HLA-B27-associated
      inflammatory diseases remains one of the strongest HLA-disease associations known
      to date. This review examines acute anterior uveitis with particular focus on HLA
      B27-associated acute anterior uveitis, including the epidemiology,
      immunopathology, association with HLA-B27 and its subtypes, clinical features,
      complications, prognosis, and potential new therapies such as anti-TNFalpha
      therapy and oral HLA-B27-peptide tolerance. There have been substantial recent
      advances in both clinical and basic scientific research in this field, including
      studies of the various animal models of acute anterior uveitis and the HLA-B27
      transgenic animals, and these are summarized in this review. To the
      ophthalmologist, HLA-B27-associated acute anterior uveitis is an important
      clinical entity that is common, afflicts relatively young patients in their most
      productive years, and is associated with significant ocular morbidity due to its
      typically recurrent attacks of inflammation and its potentially vision
      threatening ocular complications. Furthermore, to the ophthalmologist and the
      internist, HLA-B27-associated acute anterior uveitis is also of systemic
      importance due to its significant association with extraocular inflammatory
      diseases.

PMID- 15967192
TI  - You are what you eat.
AB  - Wernicke encephalopathy consists of a triad of ophthalmoplegia, ataxia, and
      altered mental status. It is caused by thiamine deficiency and although it is
      commonly seen in alcoholics, patients undergoing gastric bypass surgery for
      morbid obesity could be a new group of patients to watch for. Florid papilloedema
      and optic neuropathy are not commonly seen but are still consistent with the
      diagnosis of Wernicke encephalopathy. The most striking feature remains the
      dramatic recovery after replacement of thiamine.

PMID- 15967193
TI  - Computer and World Wide Web accessibility by visually disabled patients: problems
      and solutions.
AB  - Rapid advances in information technology have dramatically transformed the world
      during the past several decades. Access to computers and the World Wide Web is
      increasingly required for education and employment, as well as for many
      activities of daily living. Although these changes have improved society in many
      respects, they present an obstacle for visually disabled patients who may have
      significant difficulty processing the visual cues presented by modern graphical
      user interfaces. This article reviews the specific barriers to computer and Web
      access faced by visually disabled patients, describes clinical evaluation
      methods, summarizes traditional low vision methods as well as newer assistive
      computer technologies for universal accessibility, and discusses emerging
      technologies and future directions in this area.

PMID- 15967194
TI  - MRA or CTA, that's the question.
AB  - A 26-year-old woman developed a painful left pupil-involving oculomotor palsy.
      Magnetic resonance imaging of the brain and orbits with and without fat
      suppression and gadolinium and magnetic resonance angiography of the head were
      normal. A computed tomographic angiogram showed a left 7-mm posterior
      communicating artery aneurysm. The different neuroimaging modalities used to
      diagnose intracranial aneurysms are discussed.

PMID- 15967196
TI  - Glaucoma drainage devices: a systematic literature review and current
      controversies.

PMID- 15967197
TI  - Molecular biomarkers: Challenges and prospects for the future.

PMID- 15967198
TI  - Assessment of cytotoxicity by emerging impedance spectroscopy.
AB  - An on-line and continuous technique based on electric cell substrate impedance
      sensing (ECIS) was developed for measuring the concentration and time response
      function of fibroblastic V79 cells exposed to toxicants. Mercury chloride
      (HgCl(2)), cadmium chloride (CdCl(2)), benzalkonium chloride (BAK), sodium
      arsenate (Na(2)HAsO(4)), and trinitrobenzene (TNB) were used as five test models.
      The first four chemicals serve as a model for acute toxicants, and TNB represents
      a model for long-term cytotoxicity effects. Adhesion, spreading, and
      proliferation of V79 fibroblastic cells cultured on a microarray of small gold
      electrodes precoated with fibronectin were detected as resistance changes. The
      response function was derived to reflect the resistance change as a result of
      cell attachment, spreading, mitosis and cytotoxicity effect. Exposure of V79
      cells to toxicants led to alterations in cell behavior, and therefore, chemical
      cytotoxicity was easily screened by measuring the response function of the
      attached and spread cells in the presence of inhibitor. The half inhibition
      concentration, the required concentration to achieve 50% inhibition, was obtained
      from the response function to provide dynamic information about cytotoxicity
      during the course of the assay. A simple mathematical model was developed to
      describe the responses of ECIS that were related to the adhesion, spreading, and
      proliferation of V79 fibroblastic cells. The novel results of this paper are
      mainly characterized by the systematic study of several parameters including the
      cell number, detection limit, sensor sensitivity, and cytotoxicity, and they may
      motivate further research and study of ECIS sensors.

PMID- 15967199
TI  - The association between genetic polymorphisms of coproporphyrinogen oxidase and
      an atypical porphyrinogenic response to mercury exposure in humans.
AB  - Previous studies have demonstrated highly specific urinary porphyrin profile
      (UPP) changes in response to mercury (Hg) exposure in animals and human subjects
      and have defined the biochemical etiology of this effect as selective alteration
      of the heme pathway enzymes, uroporphyrinogen decarboxylase (UROD), and
      coproporphyrinogen oxidase (CPOX) by Hg in the kidney. Ongoing validation studies
      in a population of dental practitioners with low-level occupational Hg exposure
      have demonstrated the predicted UPP change among approximately 85% of subjects.
      This study focused on the genetic etiology of an atypical porphyrinogenic
      response (APR) seen among the remaining 15% of Hg-exposed subjects, characterized
      by excess excretion of 4- and 5-carboxyl porphyrins and also of the atypical
      ketoisocoproporphyrin (KICP). Automated DNA-sequencing-based assays were
      developed to examine the 7 exons and flanking intron-exon boundaries of the CPOX
      gene. Among several polymorphisms identified, an A814C variant in exon 4 encoding
      a N272H substitution was found to be predominant among subjects with the APR.
      Studies suggest that this variant CPOX preferentially converts the upstream 5
      carboxylporphyrin (5-CP) to KICP. By partially inhibiting the 5- to 4
      decarboxylation step of UROD, Hg promotes 5-CP accumulation, accounting for e
      xcess KICP excretion and the APR in Hg-exposed subjects carrying the variant CPOX
      gene. This finding represents the first report of a polymorphism in a human gene
      that modifies the effect of Hg on a biological process. The APR might serve as a
      biomarker of both Hg exposure and susceptibility to Hg toxicity.

PMID- 15967200
TI  - Metabolomic and proteomic biomarkers for III-V semiconductors: chemical-specific
      porphyrinurias and proteinurias.
AB  - A pressing need exists to develop and validate molecular biomarkers to assess the
      early effects of chemical agents, both individually and in mixtures. This is
      particularly true for new and chemically intensive industries such as the
      semiconductor industry. Previous studies from this laboratory and others have
      demonstrated element-specific alterations of the heme biosynthetic pathway for
      the III-V semiconductors gallium arsenide (GaAs) and indium arsenide (InAs) with
      attendant increased urinary excretion of specific heme precursors. These data
      represent an example of a metabolomic biomarker to assess chemical effects early,
      before clinical disease develops. Previous studies have demonstrated that the
      intratracheal or subcutaneous administration of GaAs and InAs particles to
      hamsters produces the induction of the major stress protein gene families in
      renal proximal tubule cells. This was monitored by 35-S methionine labeling of
      gene products followed by two-dimensional gel electrophoresis after exposure to
      InAs particles. The present studies examined whether these effects were
      associated with the development of compound-specific proteinuria after 10 or 30
      days following subcutaneous injection of GaAs or InAs particles in hamsters. The
      results of these studies demonstrated the development of GaAs- and InAs-specific
      alterations in renal tubule cell protein expression patterns that varied at 10
      and 30 days. At the 30-day point, cells in hamsters that received InAs particles
      showed marked attenuation of protein expression, suggesting inhibition of the
      stress protein response. These changes were associated with GaAs and InAs
      proteinuria patterns as monitored by two-dimensional gel electrophoresis and
      silver staining. The intensity of the protein excretion patterns increased
      between the 10- and 30-day points and was most pronounced for animals in the 30
      day InAs treatment group. No overt morphologic signs of cell death were seen in
      renal tubule cells of these animals. Western blot analyses of the urines with
      antibodies to the 32-, 70-, and 90-kDa stress protein families did not show the
      presence of these molecules, indicating that these proteins were not excreted in
      the urine samples. These data suggest that the observed proteinuria patterns were
      not a result of cell death and that the observed chemical-specific proteinurias
      were produced before marked cellular toxicity. These findings suggest a
      hypothesis involving GaAs and InAs interference with stress protein chaperoning
      of reabsorbed proteins for proteosomic degradation and the probable chaperoning
      of damaged intracellular proteins from renal proximal tubule cells into the
      urinary filtrate. Overall, the results of these studies provide further
      information on the nephrotoxicity of these semiconductor compounds. They also
      suggest the use of two-dimensional gel electrophoresis with silver staining of
      urinary protein patterns as a potentially useful proteomic approach to renal
      damage early in relation to intracellular proteotoxicity in kidney tubule cells.

PMID- 15967201
TI  - Role of metabolism and viruses in aflatoxin-induced liver cancer.
AB  - The use of biomarkers in molecular epidemiology studies for identifying stages in
      the progression of development of the health effects of environmental agents has
      the potential for providing important information for critical regulatory,
      clinical and public health problems. Investigations of aflatoxins probably
      represent one of the most extensive data sets in the field and this work may
      serve as a template for future studies of other environmental agents. The
      aflatoxins are naturally occurring mycotoxins found on foods such as corn,
      peanuts, various other nuts and cottonseed and they have been demonstrated to be
      carcinogenic in many experimental models. As a result of nearly 30 years of
      study, experimental data and epidemiological studies in human populations,
      aflatoxin B(1) was classified as carcinogenic to humans by the International
      Agency for Research on Cancer. The long-term goal of the research described
      herein is the application of biomarkers to the development of preventative
      interventions for use in human populations at high-risk for cancer. Several of
      the aflatoxin-specific biomarkers have been validated in epidemiological studies
      and are now being used as intermediate biomarkers in prevention studies. The
      development of these aflatoxin biomarkers has been based upon the knowledge of
      the biochemistry and toxicology of aflatoxins gleaned from both experimental and
      human studies. These biomarkers have subsequently been utilized in experimental
      models to provide data on the modulation of these markers under different
      situations of disease risk. This systematic approach provides encouragement for
      preventive interventions and should serve as a template for the development,
      validation and application of other chemical-specific biomarkers to cancer or
      other chronic diseases.

PMID- 15967202
TI  - Amplification of the Ect2 proto-oncogene and over-expression of Ect2 mRNA and
      protein in nickel compound and methylcholanthrene-transformed 10T1/2 mouse
      fibroblast cell lines.
AB  - Occupational exposure of humans to mixtures of insoluble and soluble nickel (Ni)
      compounds correlates with increased incidences of lung, sinus, and pharyngeal
      tumors. Specific insoluble Ni compounds are carcinogenic to animals by inhalation
      and induce morphological and neoplastic transformation of cultured rodent cells.
      Our objectives were to (1) understand mechanisms of nickel ion-induced cell
      transformation, hence carcinogenesis and (2) develop biomarkers of nickel ion
      exposure and nickel ion-induced cell transformation. We isolated mRNAs from green
      nickel oxide (NiO), crystalline nickel monosulfide (NiS), and 3
      methylcholanthrene (MCA) transformed C3H/10T1/2 Cl 8 cell lines, and determined
      by mRNA differential display that nine mRNA fragments were differentially
      expressed between Ni transformed and non-transformed 10T1/2 cell lines. Fragment
      R2-5 was expressed at higher steady-state levels in the transformed cell lines.
      R2-5 had 100% sequence identity to part of the coding region of Ect2, a mouse
      proto-oncogene encoding a GDP-GTP exchange factor. The 3.9-kb Ect2 transcript was
      expressed at 1.6- to 3.6-fold higher steady-state levels in four Ni transformed,
      and in two MCA-transformed, cell lines. Ect2 protein was expressed at 3.0- to 4.5
      fold higher steady-state levels in Ni-transformed and in MCA-transformed cell
      lines. The Ect2 gene was amplified by 3.5- to 10-fold in Ni transformed, and by
      2.5- to 3-fold in MCA transformed cell lines. Binding of nickel ions to enzymes
      of DNA synthesis likely caused amplification of the Ect2 gene. Ect2 gene
      amplification and over-expression of Ect2 mRNA and protein can cause microtubule
      disassembly and cytokinesis, contributing to induction and maintenance of
      morphological, anchorage-independent, and neoplastic transformation of these cell
      lines. Over-expression of Ect2 protein is a useful biomarker to detect exposure
      to nickel compounds and nickel ion-induced morphological and neoplastic cell
      transformation.

PMID- 15967203
TI  - Metallothionein gene expression in peripheral lymphocytes and renal dysfunction
      in a population environmentally exposed to cadmium.
AB  - In order to study the validity of metallothionein (MT) gene expression in
      peripheral blood lymphocytes (PBLs) as a biomarker of cadmium exposure and
      susceptibility to renal dysfunction, MT mRNA levels were measured using reverse
      transcription polymerase chain reaction (RT-PCR) in PBLs from residents living in
      a cadmium-contaminated area. MT mRNA levels were found to increase with the
      increase of blood cadmium (BCd) and urinary cadmium (UCd) levels. Basal MT mRNA
      levels were significantly correlated with the logarithm of BCd levels and the
      logarithm of UCd levels confirming that MT expression in PBLs is a biomarker of
      cadmium exposure and internal dose. An inverse relationship was observed between
      in vitro induced MT-mRNA level in PBLs and urinary N-acetyl-beta-d
      glucosaminidase (UNAG) suggesting that MT gene expression in PBLs may be used as
      a biomarker of susceptibility to renal toxicity of cadmium.

PMID- 15967204
TI  - Molecular markers of trichloroethylene-induced toxicity in human kidney cells.
AB  - Difficulties in evaluation of trichloroethylene (TRI)-induced toxicity in humans
      and extrapolation of data from laboratory animals to humans are due to the
      existence of multiple target organs, multiple metabolic pathways, sex-, species-,
      and strain-dependent differences in both metabolism and susceptibility to
      toxicity, and the lack or minimal amount of human data for many target organs.
      The use of human tissue for mechanistic studies is thus distinctly advantageous.
      The kidneys are one target organ for TRI and metabolism by the glutathione (GSH)
      conjugation pathway is responsible for nephrotoxicity. The GSH conjugate is
      processed further to produce the cysteine conjugate, S-(1,2-dichlorovinyl)-l
      cysteine (DCVC), which is the penultimate nephrotoxic species. Confluent, primary
      cultures of human proximal tubular (hPT) cells were used as the model system.
      Although cells in log-phase growth, which are undergoing more rapid DNA
      synthesis, would give lower LD(50) values, confluent cells more closely mimic the
      in vivo proximal tubule. DCVC caused cellular necrosis only at relatively high
      doses (>100 muM) and long incubation times (>24 h). In contrast, both apoptosis
      and enhanced cellular proliferation occurred at relatively low doses (10-100 muM)
      and early incubation times (2-8 h). These responses were associated with
      prominent changes in expression of several proteins that regulate apoptosis (Bcl
      2, Bax, Apaf-1, Caspase-9 cleavage, PARP cleavage) and cellular growth,
      differentiation and stress response (p53, Hsp27, NF-kappaB). Effects on p53 and
      Hsp27 implicate function of protein kinase C, the mitogen activated protein
      kinase pathway, and the cytoskeleton. The precise pattern of expression of these
      and other proteins can thus serve as molecular markers for TRI exposure and
      effect in human kidney.

PMID- 15967205
TI  - Effect of chronic intake of arsenic-contaminated water on liver.
AB  - The hepatotoxic effect of arsenic when used in therapeutic dose has long been
      recognized. We described the nature and degree of liver involvement and its
      pathogenesis due to prolonged drinking of arsenic-contaminated water in West
      Bengal, India. From hospital-based studies on 248 cases of arsenicosis,
      hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was
      the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The
      portal fibrosis was characterized by expansion of portal zones with streaky
      fibrosis, a few of which contained leash of vessels. However, portal hypertension
      was found in smaller number of cases. A cross-sectional epidemiological study was
      carried out on 7683 people residing in arsenic-affected districts of West Bengal.
      Out of these, 3467 and 4216 people consumed water-containing arsenic below and
      above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly
      higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001).
      The incidence of hepatomegaly was found to have a linear relationship
      proportionate to increasing exposure of arsenic in drinking water in both sexes
      (P < 0.001). In an experimental study, BALB/C mice were given water contaminated
      with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at
      3-month intervals. We observed progressive reduction of hepatic glutathione and
      enzymes of anti-oxidative defense system associated with lipid peroxidation.
      Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15
      months. Our studies show that prolong drinking of arsenic-contaminated water is
      associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to
      be caused by arsenic induced oxystress.

PMID- 15967206
TI  - Urinary porphyrins as biomarkers for arsenic exposure among susceptible
      populations in Guizhou province, China.
AB  - Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou
      Province contains elevated levels of arsenic. This has caused arsenicosis in
      individuals who use arsenic-contaminated coal for the purposes of heating,
      cooking and drying of food in poorly ventilated dwellings. The population at risk
      has been estimated to be approximately 200,000 people. Clinical symptoms of
      arsenicosis may include changes of skin pigmentation, hyperkeratosis of hand and
      feet, skin cancers, liver damage, persistent cough and chronic bronchitis. We
      analyzed the porphyrin excretion profile using a HPLC method in urine samples
      collected from 113 villagers who lived in Xing Ren district, a coal-borne
      arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is
      not prevalent. Urinary porphyrins were higher in the arsenic exposed group than
      those in the control group. The correlation between urinary arsenic and porphyrin
      concentrations demonstrated the effect of arsenic on heme biosynthesis resulting
      in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed
      significant increases in the excretion profile of the younger age (<20 years)
      arsenic-exposed group, suggesting that porphyrins could be used as early warning
      biomarkers of chronic arsenic exposure in humans. Greater increases of urinary
      arsenic and porphyrins in women, children and older age groups who spend much of
      their time indoors suggest that they might be at a higher risk. Whether elevated
      porphyrins could predict adverse health effects associated with both cancer and
      non-cancer end-points in chronically arsenic-exposed populations need further
      investigation.

PMID- 15967207
TI  - Non-invasive biomarkers of pulmonary damage and inflammation: Application to
      children exposed to ozone and trichloramine.
AB  - To date, airways injury or inflammation caused by air pollutants has been
      evaluated mainly by analysis of bronchoalveolar lavage, an invasive technique
      totally unsuitable to children. The assessment of respiratory risks in this
      particularly vulnerable population has thus for a long time relied on spirometric
      tests and self-reported symptoms which are relatively late and inaccurate
      indicators of lung damage. Research in the field of biomarkers is now opening new
      perspectives with the development of non-invasive tests allowing to monitor
      inflammation and damage in the deep lung. Blood tests measuring lung-specific
      proteins (pneumoproteins) such as Clara cell protein (CC16) and surfactant
      associated proteins (A, B or D) are now available to evaluate the permeability
      and/or the cellular integrity of the pulmonary epithelium. The application of
      these tests to children has recently led to the discovery of a lung epithelium
      hyperpermeability caused by trichloramine (nitrogen trichloride), an irritant gas
      contaminating the air of indoor-chlorinated pools. Serum CC16 can also serve to
      detect increases of airway permeability during short-term exposures to ambient
      ozone. Indicators measurable in exhaled air such as nitric oxide (NO) appear more
      useful to detect airway inflammation. By applying the exhaled NO test to children
      attending summer camps, we recently found that ambient ozone produces an acute
      inflammatory response in children from levels slightly lower than current air
      quality guidelines. In a study exploring the links between atopy, asthma, and
      exposure to chlorination products in indoor pools, we also found that the exhaled
      NO test can serve to detect the chronic airway inflammation associated with
      excessive exposure to trichloramine. Lung-specific proteins measurable in serum
      and markers in exhaled air represent sensitive tools that can be used to assess
      non-invasively the effects of air pollutants on the respiratory tract of
      children.

PMID- 15967208
TI  - Biomarkers of cadmium and arsenic interactions.
AB  - Advances in proteomics have led to the identification of sensitive urinary
      biomarkers of renal dysfunction that are increasingly used in toxicology and
      epidemiology. Recent animal data show that combined exposure to inorganic arsenic
      (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure
      to each of the agents alone. In order to examine if similar interaction occurs in
      humans, renal dysfunction was studied in population groups (619 persons in total)
      residing in two metal contaminated areas in China: mainly a Cd contaminated area
      in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou
      province (G-area). Nearby control areas without excessive metal exposure were
      also included. Measurements of urinary beta(2)-microglobulin (UB2MG), N-acetyl
      beta-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB)
      were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs)
      were analyzed by graphite-furnace atomic absorption spectrometry. Urinary
      inorganic As and its mono- and di-methylated metabolites (UIAs) were determined
      by Hydride generation. Results. As expected, the highest UCd values occurred in Z
      area (Geometric mean, GM 11.6 microg/g crea) while the highest UTAs values
      occurred in G-area (GM = 288 microg/g crea). Statistically significant increases
      compared to the respective control area were present both for UTAs, UCd and for
      UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in
      Z area. In G-area, there was a clear dose-response pattern both in relation to
      UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction
      effect between As and Cd was demonstrated at higher levels of a combined exposure
      to As and Cd enhancing the effect on the kidney. In Z-area an increased
      prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but
      no relationship to UTAs was found. A statistically significant relationship
      between UIAs and UB2MG was found among women in this area and an interaction
      between As and Cd was indicated for B2MG. Conclusion. The present studies, which
      employed sensitive biomarkers of renal dysfunction, give support to the idea that
      human co-exposure to Cd and inorganic arsenic gives rise to more pronounced renal
      damage than exposure to each of the elements alone, but further studies are
      needed to establish and clarify this interaction.

PMID- 15967209
TI  - Biomarkers of exposure, effect, and susceptibility of arsenic-induced health
      hazards in Taiwan.
AB  - Long-term exposure to inorganic arsenic from drinking water has been documented
      to induce cancers and vascular diseases in a dose-response relationship. A series
      of molecular environmental epidemiological studies have been carried out to
      elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related
      health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers
      for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar
      hyperkeratosis are for long-term (many years) internal dose, and percentage of
      monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be
      considered as an exposure marker for biologically effective dose. The biomarkers
      of early biological effects of ingested inorganic arsenic included blood levels
      of reactive oxidants and anti-oxidant capacity, genetic expression of
      inflammatory molecules, as well as cytogenetic changes including sister chromatid
      exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both
      mutation type and hot spots of p53 gene were significantly different in arsenic
      induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances
      analyzed by comparative genomic hybridization and the frequency of loss of
      heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic
      induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced
      health hazards included genetic polymorphisms of enzymes involved in xenobiotic
      metabolism, DNA repair, and oxidative stress, as well as serum level of
      carotenoids. Gene-gene and gene-environment interactions are involved in arsenic
      induced health hazards through toxicological mechanisms including genomic
      instability and oxidative stress.

PMID- 15967210
TI  - Measurement of genotoxic air pollutant exposures in street vendors and school
      children in and near Bangkok.
AB  - The effects of air pollution on human health are a great concern, particularly in
      big cities with severe traffic problems such as Bangkok, Thailand. In this study,
      exposure to genotoxic compounds in ambient air was studied by analysis of
      particle-associated polycyclic aromatic hydrocarbons (PAHs) and benzene through
      direct measurement of concentrations in air as well as through the use of
      different biomarkers of exposure: urinary 1-hydroxypyrene (1-OHP) for PAHs and
      urinary t,t-muconic acid (t,t-MA) for benzene. The study was conducted in various
      susceptible groups of the population with different occupations in 5 traffic
      congested areas of Bangkok, as well as in primary school children. The level of
      total PAHs on the main roads at various sites ranged from 7.10 to 83.04 ng/m(3),
      while benzene levels ranged from 16.35 to 49.25 ppb. In contrast, ambient levels
      in nearby temples, the control sites, ranged from 1.67 to 3.04 ng/m(3) total PAHs
      and 10.16 to 16.25 ppb benzene. Street vendors selling clothes were exposed to
      16.07 +/- 1.64 ng/m(3) total PAHs and 21.97 +/- 1.50 ppb benzene, levels higher
      than in monks and nuns residing in nearby temples (5.34 +/- 0.65 ng/m(3) total
      PAHs and 13.69 +/- 0.77 ppb benzene). Grilled-meat vendors in the same area were
      exposed to both total PAHs and benzene at even higher levels, possibly due to
      additional formation of PAHs during the grilling of meat (34.27 +/- 7.02 ng/m(3)
      total PAHs; 27.49 +/- 2.72 ppb benzene). At the end of the workday, urinary 1-OHP
      levels in street vendors (0.12 and 0.15 micromol/mol creatinine in clothes and
      grilled-meat vendors, respectively) were significantly higher than in controls
      (0.04 micromol/mol creatinine; P < 0.01). Afternoon urinary t,t-MA levels in both
      groups of street vendors (0.12 mg/g creatinine) were also significantly higher
      than in controls (0.08 mg/g creatinine; P < 0.05). School children from two
      schools in Bangkok were exposed to total PAHs and benzene at levels of 6.70 +/-
      0.47 ng/m(3) and 4.71 +/- 0.25 ppb, respectively, higher than those to which
      children living outside the city were exposed (1.25 +/- 0.24 ng/m(3) total PAHs;
      2.10 +/- 0.16 ppb benzene). At the end of the school day, levels of urinary 1-OHP
      and t,t-MA were significantly higher (P < 0.001 and P < 0.01, respectively) in
      Bangkok school children (0.23 micromol/mol creatinine and 0.27 mg/g creatinine,
      respectively) than in school children from outside Bangkok (0.10 micromol/mol
      creatinine and 0.08 mg/g creatinine, respectively).

PMID- 15967211
TI  - An overview of children as a special population--relevance to predictive
      biomarkers.
AB  - There has been an increasing focus on children as a special population in the
      fields of toxicology and epidemiology. At the same time, there has been
      considerable improvement in the technology for defining normal development and
      pathways of pathogenesis. Increased support of these areas has culminated in
      stronger research programs and greater professional involvement in addressing the
      specific challenges of applying new techniques and data to the improvement of
      children's health. Part of these challenges relates to the ever changing
      environment of the child. Not only does a child's anatomy, physiology, and
      metabolism change with time, but their lifestyle and awareness change as well.
      All of these can have a significant impact on a child's exposure and the
      potential of that exposure to have an effect on health and development. This
      paper will provide a brief overview of the susceptibility of the child relative
      to sensitive developmental life stages, the changing nature of exposure
      parameters during development, and how these factors can impact the relevance of
      predictive biomarkers of chemical toxicity in children.

PMID- 15967212
TI  - Searching for biomarkers of developmental toxicity with microarrays: normal eye
      morphogenesis in rodent embryos.
AB  - Gene expression arrays reveal the potential linkage of altered gene expression
      with specific adverse effects leading to disease phenotypes. But how closely do
      microarray data reflect early physiological or pharmacological measures that
      predict toxic event(s)? To explore this issue, we have undertaken experiments in
      early mouse embryos exposed to various teratogens during neurulation stages with
      the aim of correlating large-scale changes in gene expression across the critical
      period during exposure. This study reports some of the large-scale changes in
      gene expression that can be detected in the optic rudiment of the developing
      mouse and rat embryo across the window of development during which the eye is
      exceedingly sensitive to teratogen-induced micro-/anophthalmia. Microarray
      analysis was performed on RNA from the headfold or ocular region at the optic
      vesicle and optic cup stages when the ocular primordium is enriched for Pax-6, a
      master control gene for eye morphogenesis. Statistical selection of
      differentially regulated genes and various clustering techniques identified
      groups of genes in upward or downward trajectories in the normal optic primordium
      during early eye development in mouse and rat species. We identified 165 genes
      with significant differential expression during eye development, and a smaller
      subset of 58 genes that showed a tight correlation between mouse-rat development.
      Significantly over-represented functional categories included fatty acid
      metabolism (up-regulated) and glycolysis (down-regulated). From studies such as
      these that benchmark large-scale gene expression during normal embryonic
      development, we may be able to identify the panel of biomarkers that best
      correlate with species differences and the risks for developmental toxicity.

PMID- 15967213
TI  - Biomarkers to assess potential developmental immunotoxicity in children.
AB  - Clinical tests are readily available for assessing severe loss of immune function
      in children with diseases such as AIDS or primary immunodeficiency. However tests
      that could reliably identify subtle immune changes, as might be expected to
      result from exposure to developmental immunotoxic agents, are not readily
      available. A number of tests are described which we believe have potential
      applicability for epidemiological studies involving developmental immunotoxicity.
      Several of the tests, such as T cell receptor rearrangement excision circles
      (TRECs) and cytokine measurements, while highly relevant from a biological
      standpoint, may be precluded from use at the current time, for either technical
      issues or insufficient validation. Immunophenotyping and measurement of serum
      immunoglobulin levels, on the other hand, are well validated. Yet they may
      require extraordinary care in experimental design and technical performance in
      order to obtain data that would consistently detect subtle changes, as these
      tests are not generally considered highly sensitive. Quantification of the immune
      response to childhood vaccine, while up to the present used sparingly, may
      represent an excellent indicator for developmental immunotoxicity when conducted
      under appropriate conditions.

PMID- 15967214
TI  - Molecular biomarkers for the study of childhood leukemia.
AB  - Various specific chromosome rearrangements, including t(8;21), t(15;17), and
      inv(16), are found in acute myeloid leukemia (AML) and in childhood acute
      lymphocytic leukemia (ALL), t(12;21) and t(1;19) are common. We sequenced the
      translocation breakpoints of 56 patients with childhood ALL or AML harboring
      t(12;21), t(8;21), t(15;17), inv(16), and t(1;19), and demonstrated, with the
      notable exception of t(1;19), that these rearrangements are commonly detected in
      the neonatal blood spots (Guthrie cards) of the cases. These findings show that
      most childhood leukemias begin before birth and that maternal and perinatal
      exposures such as chemical and infectious agents are likely to be critical.
      Indeed, we have reported that exposure to indoor pesticides during pregnancy and
      the first year of life raises leukemia risk, but that later exposures do not. We
      have also examined aberrant gene methylation in different cytogenetic subgroups
      and have found striking differences between them, suggesting that epigenetic
      events are also important in the development of some forms of childhood leukemia.
      Further, at least two studies now show that the inactivating NAD(P)H:quinone
      acceptor oxidoreductase (NQO1) C609T polymorphism is positively associated with
      leukemias arising in the first 1-2 years of life and polymorphisms in the 5,10
      methylenetetrahydrofolate reductase (MTHFR) gene have been associated with adult
      and childhood ALL. Thus, low folate intake and compounds that are detoxified by
      NQO1 may be important in elevating leukemia risk in children. Finally, we are
      exploring the use of proteomics to subclassify leukemia, because cytogenetic
      analysis is costly and time-consuming. Several proteins have been identified that
      may serve as useful biomarkers for rapidly identifying different forms of
      childhood leukemia.

PMID- 15967215
TI  - Biomarkers in assessing residential insecticide exposures during pregnancy and
      effects on fetal growth.
AB  - The Columbia Center for Children's Environmental Health is using a combination of
      environmental and biologic measures to evaluate the effects of prenatal
      insecticide exposures among urban minorities in New York City. Of the 571 women
      enrolled, 85% report using some form of pest control during pregnancy and 46%
      report using exterminators, can sprays, and/or pest bombs. Chlorpyrifos,
      diazinon, and propoxur were detected in 99.7-100% of 48-h personal air samples
      collected from the mothers during pregnancy (n = 394) and in 39-70% of blood
      samples collected from the mothers (n = 326) and/or newborns (n = 341) at
      delivery. Maternal and newborn blood levels are similar and highly correlated (r
      = 0.4-08, P < 0.001). Levels of insecticides in blood samples and/or personal air
      samples decreased significantly following the 2000-2001 U.S. Environmental
      Protection Agency's regulatory actions to phase out residential use of
      chlorpyrifos and diazinon. Among infants born prior to 1/1/01, birth weight
      decreased by 67.3 g (95% confidence interval (CI) -116.6 to -17.8, P = 0.008) and
      birth length decreased by 0.43 centimeters (95% CI, -0.73 to -0.14, P = 0.004)
      for each unit increase in log-transformed cord plasma chlorpyrifos levels.
      Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for
      relative potency) were also inversely associated with birth weight and length (P
      </= 0.007). Birth weight averaged 215.1 g less (95% CI -384.7 to -45.5) among
      those with the highest exposures compared to those without detectable levels. No
      association was seen between birth weight and length and cord plasma chlorpyrifos
      or diazinon among newborns born after 1/1/01 (P > 0.8). Results support recent
      regulatory action to phase out residential uses of these insecticides.

PMID- 15967216
TI  - Biomarkers of adult and developmental neurotoxicity.
AB  - Neurotoxicity may be defined as any adverse effect on the structure or function
      of the central and/or peripheral nervous system by a biological, chemical, or
      physical agent. A multidisciplinary approach is necessary to assess adult and
      developmental neurotoxicity due to the complex and diverse functions of the
      nervous system. The overall strategy for understanding developmental
      neurotoxicity is based on two assumptions: (1) significant differences in the
      adult versus the developing nervous system susceptibility to neurotoxicity exist
      and they are often developmental stage dependent; (2) a multidisciplinary
      approach using neurobiological, including gene expression assays,
      neurophysiological, neuropathological, and behavioral function is necessary for a
      precise assessment of neurotoxicity. Application of genomic approaches to
      developmental studies must use the same criteria for evaluating microarray
      studies as those in adults including consideration of reproducibility,
      statistical analysis, homogenous cell populations, and confirmation with non
      array methods. A study using amphetamine to induce neurotoxicity supports the
      following: (1) gene expression data can help define neurotoxic mechanism(s), (2)
      gene expression changes can be useful biomarkers of effect, and (3) the site
      selective nature of gene expression in the nervous system may mandate assessment
      of selective cell populations.

PMID- 15967217
TI  - Molecular epidemiology biomarkers--sample collection and processing
      considerations.
AB  - Biomarker studies require processing and storage of numerous biological samples
      with the goals of obtaining a large amount of information and minimizing future
      research costs. An efficient study design includes provisions for processing of
      the original samples, such as cryopreservation, DNA isolation, and preparation of
      specimens for exposure assessment. Use of standard, two-dimensional and
      nanobarcodes and customized electronic databases assure efficient management of
      large sample collections and tracking results of data analyses. Standard
      operating procedures and quality control plans help to protect sample quality and
      to assure validity of the biomarker data. Specific state, federal and
      international regulations are in place regarding research with human samples,
      governing areas including custody, safety of handling, and transport of human
      samples. Appropriate informed consent must be obtained from the study subjects
      prior to sample collection and confidentiality of results maintained. Finally,
      examples of three biorepositories of different scale (European Cancer Study,
      National Cancer Institute and School of Public Health Biorepository, University
      of California, Berkeley) are used to illustrate challenges faced by investigators
      and the ways to overcome them. New software and biorepository technologies are
      being developed by many companies that will help to bring biological banking to a
      new level required by molecular epidemiology of the 21st century.

PMID- 15967218
TI  - Development of a biomarkers database for the National Children's Study.
AB  - The National Children's Study (NCS) is a federally-sponsored, longitudinal study
      of environmental influences on the health and development of children across the
      United States (). Current plans are to study approximately 100,000 children and
      their families beginning before birth up to age 21 years. To explore potential
      biomarkers that could be important measurements in the NCS, we compiled the
      relevant scientific literature to identify both routine or standardized
      biological markers as well as new and emerging biological markers. Although the
      search criteria encouraged examination of factors that influence the breadth of
      child health and development, attention was primarily focused on exposure,
      susceptibility, and outcome biomarkers associated with four important child
      health outcomes: autism and neurobehavioral disorders, injury, cancer, and
      asthma. The Biomarkers Database was designed to allow users to: (1) search the
      biomarker records compiled by type of marker (susceptibility, exposure or
      effect), sampling media (e.g., blood, urine, etc.), and specific marker name; (2)
      search the citations file; and (3) read the abstract evaluations relative to our
      search criteria. A searchable, user-friendly database of over 2000 articles was
      created and is publicly available at: . PubMed was the primary source of
      references with some additional searches of Toxline, NTIS, and other reference
      databases. Our initial focus was on review articles, beginning as early as 1996,
      supplemented with searches of the recent primary research literature from 2001 to
      2003. We anticipate this database will have applicability for the NCS as well as
      other studies of children's environmental health.

PMID- 15967220
TI  - Overall assessment of regeneration in peripheral nerve lesion repair using fibrin
      glue, suture, or a combination of the 2 techniques in a rat model. Which is the
      ideal choice?
AB  - BACKGROUND: Nerve repair with fibrin glue is an alternative to conventional
      suture technique, although there is no definitive experimental evaluation of the
      2 techniques. This experimental study was undertaken to evaluate nerve
      regeneration after sciatic nerve repair with fibrin glue and to compare it with
      repair performed with suture and a combination of both techniques. METHODS:
      Eighty-six male Wistar rats were subjected to right sciatic nerve transection and
      immediate repair with 4-stitch nylon suture (group A), fibrin glue (group B), or
      a combination of both techniques (group C). Walking track analysis to access
      functional recovery was performed preoperatively and 12 weeks postoperatively.
      Before nerve section and after a 24-week interval, the nerve and motor action
      potentials (MAPs) were evaluated. Histomorphometric evaluation was carried out 24
      weeks after nerve section. Differences between groups were evaluated for
      significance using the Kruskal-Wallis or analysis of variance methods. RESULTS:
      Animals of group B presented better results than those of group A when the
      functional evaluation was applied (P < .05). When nerve conduction velocity was
      evaluated at reoperation and the ratio between conduction velocity at reoperation
      and before the nerve section in MAP evaluation were measured and compared in the
      3 groups, the rats of group B presented better results than those of group A (P <
      .05). Animals of group C presented better results than those of group A when the
      ratio between nerve conduction velocities was considered. There was no difference
      between the nerve repair methods when histomorphometric evaluation was performed.
      CONCLUSION: In a rat model, nerve repair using fibrin glue provided better
      conditions for regeneration than suture after sciatic nerve transection.

PMID- 15967222
TI  - The controversial arcade of Struthers.
AB  - BACKGROUND: The occurrence, incidence, and relevance of the arcade of Struthers
      as a point of compression of the ulnar nerve at the elbow region are still
      controversial. This study was conducted to determine the incidence of the arcade
      of Struthers on anatomical dissections and to analyze the data from the
      literature concerning this anatomical structure. METHODS: The medial surface of
      the distal third of the arm was dissected in 60 limbs of frozen nonfixed
      cadavers, and the region was surveyed for the existence of musculotendinous and
      fibrous structures resembling an arch. When present, its appearance, extension,
      distance from the medial humeral epicondyle, and relation with the ulnar nerve
      were recorded. RESULTS: A musculotendinous arcade, defined as arcade of
      Struthers, was identified in 8 limbs (13.5%). The extension of the arcade ranged
      from 2.5 to 5.0 cm (median 3.75 cm), and the distance between its distal limit
      and the medial humeral epicondyle ranged from 3 to 10 cm (median 6.82 cm). No
      evidence of ulnar nerve compression was found in the specimens where an arcade
      was identified. CONCLUSION: Although the use of the term arcade of Struthers
      seems to be historically incorrect, this relatively rare anatomical structure
      does exist. Well recognized as a potential secondary site of compression of the
      ulnar nerve at the elbow in patients submitted to anterior transposition surgery,
      its importance as a primary site of compression probably has been underestimated.

PMID- 15967223
TI  - Endothelin-1 levels in plasma and cerebrospinal fluid of patients with cerebral
      vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Plasma and cerebrospinal fluid (CSF) concentrations of endothelin-1
      (ET-1) were measured in patients with subarachnoid hemorrhage (SAH) after
      aneurysmal rupture and compared with levels of ET-1 in volunteers. We analyze the
      relationship between levels of ET-1 in both CSF and plasma with the risk of
      developing cerebral vasospasm (CVS). METHODS: Cerebrospinal fluid and blood
      samples were collected from 30 selected patients after SAH and from 10 healthy
      volunteers who were used as control. All samples were stored at -70 degrees C and
      the levels of ET-1 in CSF and blood were measured by using enzyme-linked
      immunosorbent assay and Western blot. All patients were submitted to angiography
      to confirm vasospasm. RESULTS: From the 30 patients admitted at different days of
      SAH, 18 (60%) developed clinical CVS and 10 (33%) presented angiographic CVS. The
      levels of ET-1 in the CSF were significantly higher (P = .0001) in patients
      (1.618 +/- 1.05 fmol/mL) than in controls (0.365 +/- 0.328 fmol/mL). There was
      statistical difference (P < .05) in CSF levels of ET-1 between each group of the
      Hunt-Hess scale and controls. The mean plasma concentration of ET-1 was similar
      (P > .05) in the control group (1.531 +/- 0.753 fmol/mL) and in patients with SAH
      (1.920 +/- 1.15 fmol/mL). CONCLUSIONS: These findings indicate that a significant
      rise in ET-1 levels in the CSF, but not in the plasma, occurs in patients who
      develop CVS after SAH. Our observation suggests that ET-1 might be involved in
      the pathogenesis of SAH-associated CVS.

PMID- 15967225
TI  - Pathophysiology of posttraumatic temporal lobe lesions.
AB  - BACKGROUND: Posttraumatic parenchymal lesions in the temporal lobe may cause
      neurologic deterioration. An analysis was made of the natural evolution of this
      type of lesion, with emphasis on its 2 components: hemorrhage (hyperdense on
      computed tomography [CT]), and edema and necrosis (hypodense on CT). The clinical
      repercussions were studied, and the factors that might influence such evolution
      were investigated. METHODS: Forty head-injured patients with temporal lobe
      lesions admitted within 12 hours after the injury were selected in a prospective
      manner. Computed tomography scans were systematically repeated within the first
      36 hours and at 7 and 30 days postinjury. Factors such as interval between injury
      and the first CT scan, age, velocity of the injury, alcohol consumption,
      coagulation abnormalities, and the presence of decompressive measures were
      compared between the patients that had enlargement of the hemorrhage and those
      who did not. Increase in hypodensity was compared with that in hyperdensity.
      RESULTS: Fourteen patients showed enlargement of the hemorrhage. In all cases but
      one, the interval between injury and admission was 3 hours or less. Other factors
      had no statistical significance as predisposing causes for such enlargement. In
      approximately half of the cases, the hypodense component increased in the first
      36 hours and continued increasing until the end of the first week. Evolution of
      the hypodense component was not dependent on behavior of the hemorrhage, surgical
      drainage, or diameter of the hemorrhagic lesion. CONCLUSIONS: The natural
      evolution of the hyperdense component of temporal lobe lesions was to enlarge
      within the first few hours after the injury. Edema and necrosis developed more
      slowly and with no significant clinical manifestations.

PMID- 15967227
TI  - Cervical spondylotic myelopathy: 10 years of prospective outcome analysis of
      anterior decompression and fusion.
AB  - BACKGROUND: Fifty-one patients with cervical spondylotic myelopathy (CSM) treated
      by anterior cervical corpectomy with fusion (ACWF) at our institution were
      included in a study during a period of 10 years to evaluate neurological,
      anatomical, and functional outcomes including satisfaction levels. METHODS: We
      have completed a prospective evaluation of 39 patients with spondylotic
      myelopathy submitted to ACWF during the period of 1989-2000. The data were
      analyzed for age, duration of symptoms, severity of preoperative neurological
      deficit, and single-level or multilevel compressive status looking for possible
      association with prognostic surrogate data and clinical outcome that were
      evaluated with the Nurick score and a survey of level of satisfaction. RESULTS:
      Of the 51 patients, 39 fullfilled the intended follow-up being 28 men (71.8%) and
      11 women (28.2%). The average age was 63.5 years. Duration of symptoms ranged
      from 1 to 240 months (mean, 38.1 months). The mean preoperative Nurick scale
      score was 2.97; the mean postoperative score was 2.1. The most frequently
      involved vertebral body was C5 (71.7%). The follow-up period was longer than 18
      months for all patients. Postoperative nonneurological complications occurred in
      8 patients (15.6%). The mortality rate was 1.9% (n = 1). Postoperative results
      showed improvement in 25 patients (64.1%), no change in 13 (33.3%), and worsening
      in 1 (2.6%). The correlation coefficient of preoperative and postoperative Nurick
      scores was 0.733 (R(2) = 0.53). Of the 39 patients, 31 answered the questionnaire
      for quality of life-19 (61.2%) were very satisfied, 6 were satisfied (19.35%),
      and 6 were not satisfied (19.35%). CONCLUSION: Most patients (80.6%) were very
      satisfied or satisfied with the outcome and would decide again for the surgery
      (87%) if the results were previously known. Anterior cervical corpectomy with
      fusion was a reliable and rewarding procedure for CSM, with functional
      improvement in most patients. Excellent long-term outcome results in cervical
      fusion can be achieved without the use of hardware instrumentation.

PMID- 15967231
TI  - Monitoring of activated coagulation time in carotid endarterectomy.
AB  - BACKGROUND: The objective of the present study was to evaluate the efficacy of
      monitoring activated coagulation time (ACT) during carotid endarterectomy (CEA)
      in reducing surgical risks and complications. METHODS: A total of 175 consecutive
      patients who had CEA between July 2002 and January 2004 were studied. Activated
      coagulation time was monitored during the procedure in all patients. The results
      were compared with the data reported in the literature, and with those obtained
      in 2 previous series, totaling 1924 patients treated at the same service before
      the use of ACT. RESULTS: Only 4 of the 175 patients had cerebral ischemia, with 3
      of them almost completely recovering during hospitalization. Significant
      morbidity was 0.6% and mortality was 0.6%. No statistically significant
      difference in the incidence of cerebral ischemia or death was observed between
      symptomatic and asymptomatic patients. In the 2 previous series used for
      comparison, operated by the same author, we found 0.7% and 0.8% of significant
      morbidity and 1.4% and 2.6% of mortality, respectively. Most series in the
      literature have shown a higher significant morbidity than the present one, mainly
      in symptomatic patients. The incidence of hematoma in the present series was
      5.7%, only 3 (1.7%) of them being significant. No increase in the frequency of
      hematomas was observed in cases where heparin was not reversed or in those using
      a shunt. In the 2 other previous series, the incidence of hematomas was 1.5% and
      3.6%. CONCLUSIONS: Activated coagulation time monitoring during CEA was effective
      in evaluating the level of heparinization of patients during surgery and the
      immediate postoperative period. The comparison of the present series with the
      literature and with the previous series of the same service, before the use of
      ACT, permits also to conclude that the control of the level of heparinization
      seems to reduce the risk of perioperative and immediate postoperative ischemia.
      In addition, ACT monitoring also seems to be effective in diminishing the risk of
      postoperative cervical hematoma.

PMID- 15967232
TI  - Borderline personality disorder characteristics in young adults with recurrent
      mood disorders: a comparison of bipolar and unipolar depression.
AB  - BACKGROUND: In young adults it can be difficult to differentiate between an early
      bipolar illness and borderline personality disorder. There are considerable areas
      of clinical overlap between cyclothymic temperament, bipolar-spectrum disorders
      and borderline characteristics. The aim of this study was to measure borderline
      characteristics in young adults during an index depressive episode and to compare
      three diagnostic groups: DSM-IV bipolar affective disorder (BPAD); bipolar
      spectrum disorder (BSD); and DSM-IV recurrent major depressive disorder (MDD).
      METHODS: Eighty-seven young adults with a current episode of major depression and
      at least one previous episode of depression were recruited from consecutive
      referrals to a psychiatric clinic. Diagnoses were based on the Structured
      Clinical Interview for DSM-IV (SCID-1) and recently proposed structured
      diagnostic criteria for BSD. All patients also completed the borderline questions
      from the screening questionnaire of the International Personality Disorders
      Examination (IPDE). RESULTS: Diagnostically, the cohort of 87 patients divided
      into three groups: 14 with BPAD; 27 with BSD; and 46 with MDD. None of the
      subjects fulfilled DSM-IV or ICD-10 diagnostic criteria for personality disorder
      and all three groups were well matched in terms of age, gender distribution,
      ethnicity, socioeconomic and educational status, age at onset of illness, and
      severity of index depressive episode. Both of the bipolar-depressed groups
      reported significantly higher median levels of borderline characteristics than
      the MDD group (p<0.0001). Three of the borderline characteristics emerged as
      potentially useful in differentiating bipolar depression from unipolar
      depression: 'I've never threatened suicide or injured myself on purpose'
      (sensitivity=0.93; positive predictive value [PPV]=56.7); 'I have tantrums or
      angry outbursts' (sensitivity 0.66; PPV=65.6%); and 'Giving in to some of my
      urges gets me into trouble' (sensitivity=0.76; PPV=59.6%). LIMITATIONS: All of
      the subjects were recruited from a university health service clinic and as such
      are unlikely to be representative of patients from more diverse socio-economic
      backgrounds. No structured diagnostic assessment of personality disorder was
      administered. The diagnostic criteria for BSD are not yet fully validated.
      CONCLUSIONS: Young adults with bipolar depression exhibit significantly higher
      levels of borderline personality pathology than those with unipolar depression.
      Those borderline screening questions that reflect cyclothymic characteristics or
      depressive mixed states may be of practical use to clinicians in helping to
      differentiate between bipolar depression and unipolar depression in young adults.

PMID- 15967233
TI  - High harm avoidance and low self-directedness in euthymic young adults with
      recurrent, early-onset depression.
AB  - BACKGROUND: The personality dimensions of harm avoidance (HA) and self
      directedness (SD), as measured by the Temperament and Character Inventory (TCI),
      have been widely associated with depression and there is preliminary evidence
      that they may represent trait markers for depression. However, many studies in
      this area are limited by the use of heterogeneous samples of depressed patients
      and by the confounding effect of depressed mood during personality testing. The
      current study compares TCI personality dimension scores in a group of euthymic
      young adults with recurrent early-onset major depressive disorder (RE-MDD) to
      well-matched euthymic controls. METHODS: Fifty-two young adults with a past
      history of RE-MDD were recruited from consecutive referrals to a psychiatric
      clinic at a university health service. Eighty nine controls were also recruited.
      Euthymia was established in patients by a score of less than 9 on the Hamilton
      Rating Scale for Depression (HRSD) and in controls by a Becks Depression
      Inventory (BDI) score of less than 10. All participants completed the TCI-125.
      RESULTS: Patients and controls were well matched in terms of sociodemographic
      profile. Euthymic RE-MDD patients scored significantly higher than controls on
      the temperament dimension of harm avoidance (HA; mean score 14.5 versus 7.8,
      p<0.0001) and significantly lower than controls on the character dimension of
      self-directedness (SD; mean score 14.1 versus 19.9, p<0.0001). Covariance
      analysis suggested that both HA and SD contributed independently to the familial
      risk of depression. LIMITATIONS: Subjects and controls all came from relatively
      affluent social backgrounds-these findings may not generalise to more
      socioeconomically diverse populations. The possibility of a 'scarring effect' of
      depressive episodes on self-reported personality dimension scores cannot be
      excluded. CONCLUSIONS: High HA and low SD represent trait markers for liability
      to recurrent major depressive disorder in young adults. Further research is
      needed to replicate these findings and to assess the contribution that the
      experience of depressive episodes makes to self-reported personality dimension
      scores.

PMID- 15967234
TI  - A case-control study of 92 cases of in-patient suicides.
AB  - BACKGROUND: A significant number of patients committed suicide while receiving in
      patient treatment in psychiatric hospitals. Most previous studies on psychiatric
      in-patient suicides were conducted in the West. This study aimed to describe the
      characteristics and identify risk factors of suicides occurring during
      psychiatric in-patient care in Hong Kong. METHOD: The case record data of suicide
      cases (Coroner's verdicts of suicides and undetermined deaths) from all public
      psychiatric hospitals in the entire region within a 3 years' period (N=93) were
      compared with matched controls. RESULTS: In-patient suicide rate was 269/100,000
      admissions. Majority had schizophrenia. Suicide usually occurred after the first
      month of admission, during leave, and by jump from heights. There were little
      case-control differences in treatment received. Multiple conditional logistic
      regression found 5 risk factors: previous history of deliberate self-harm
      (OR=4.60, 95% CI=1.57-13.5); admitted because of suicidal behaviour (OR=3.92, 95%
      CI=1.3-11.9); depressive symptoms at time of suicide (OR=8.53, 95% CI=1.4-52);
      away without leave at anytime during index admission (OR=17, 95% CI=1.76-163);
      and extrapyramidal side effects/akathisia at time of suicide (OR=10.8, 95%
      CI=1.75-66.7). LIMITATIONS: Retrospective case record review depended on non
      standardized and variable quality of case notes entry. Matching for hospitals in
      this study would make the comparison between hospitals impossible. Although this
      is the second largest case-control study of psychiatric in-patient suicide, the
      estimated power suggested subtle risk factors would be missed. CONCLUSION:
      Majority of in-patient suicides occurred at a time of perceived low risk. A high
      sensitivity to the risk of suicide and vigorous treatment of depressive symptoms
      were indicated. The care processes during the index admission could bear strong
      influences on the risk of in-patient suicides.

PMID- 15967235
TI  - Is treatment-associated hypomania rare with duloxetine: secondary analysis of
      controlled trials in non-bipolar depression.
AB  - BACKGROUND: Selective serotonin (5-HT) and norepinephrine (NE) reuptake
      inhibitors (SNRIs) like duloxetine have the efficacy of tricyclic antidepressants
      (TCAs) with a more tolerable side-effect profile. Bipolar disorder is often
      undetected, with the most common misdiagnosis being unipolar depression. Studies
      have suggested that treatment of bipolar and unipolar depression with
      heterocyclic TCAs may increase the risk of switch rate to mania. Studies of
      antidepressants in unipolar major depression show a small risk of mania or
      hypomania, presumably because some bipolar depressives were mistakenly studied.
      This study investigated the rate of hypomania, mania, and hypomanic-like symptoms
      observed during treatment with duloxetine in patients with major depression.
      METHODS: This was a retrospective analysis of data from eight placebo-controlled,
      double-blind, randomized clinical trials of duloxetine in patients with non
      bipolar major depression. LIMITATIONS: The studies were of limited duration.
      Manic or hypomanic symptoms were not elicited using standardized mania rating
      scale instruments. RESULTS: One case of mania occurred in the placebo group
      (0.1%), and two cases of hypomania were observed in the duloxetine-treated group
      (0.2%). Among hypomanic-like symptoms, only insomnia was significantly higher in
      the duloxetine group than in the placebo group (p<0.05). CONCLUSIONS: Duloxetine
      was associated with a low incidence of treatment-emergent hypomania, mania, or
      hypomanic-like symptoms in patients with major depressive disorder (MDD). The low
      incidence reported here may be due to greater diagnostic diligence on the part of
      the investigators. It is possible that the cases reported likely reflect
      inclusion of misdiagnosed bipolar II patients rather than true unipolar MDD
      cases. The effect of duloxetine in patients with bipolar depression is not known.

PMID- 15967236
TI  - RT-PCR-RFLP for genetic diversity analysis of Tunisian Grapevine fanleaf virus
      isolates in their natural host plants.
AB  - Genetic diversity was characterized in 20 isolates of Grapevine fanleaf virus
      (GFLV) recovered from naturally infected grapevine plants (Vitis vinifera) in the
      North of Tunisia. Viral RNAs were isolated by oligoprobe capture, and a 605 bp
      fragment containing a part of the viral coat protein gene was amplified by RT
      PCR. Sequence variation among isolates was characterized by restriction fragment
      length polymorphism (RFLP) analysis and confirmed by sequencing. The GFLV
      infections are found as a complex mixture of closely related genomes. In further
      studies, RFLP analyses of virus isolates using AluI showed that GFLV populations
      in Tunisian vineyards consist of two restrictotypes corresponding to distinct sub
      populations Sp1 and Sp2. The relative field distribution of these sub-populations
      showed that Sp2 was more abundant. Individual genomes were recovered by cloning
      the RT-PCR products. The sequences were found to vary from each other by as much
      as 11%. Cloning from mixed infections showed that Sp2 are also predominant.

PMID- 15967237
TI  - Rapid detection of infectious adenoviruses by mRNA real-time RT-PCR.
AB  - Adenoviruses are among the most persistent and ubiquitous viruses in water and
      wastewater, but some of them are difficult to detect due to non-cytopathogenicity
      and slow growth in cell cultures. A TaqMan real-time RT-PCR method in conjunction
      with cell culture infectivity was developed to rapidly detect mRNA produced by
      infectious adenoviruses in water samples. Only infectious adenoviruses were
      detected by this method, based on their ability to produce mRNA during
      replication in cell culture. The mRNA of Ad41 was detected as soon as 3 days
      after infection at levels as low as 5 infectious units (IU) per cell culture. In
      order to confirm that our methods detected only infectious viruses, 1-ml volumes
      of 10(4)IU of Ad41 were exposed to different free chlorine doses. No mRNA was
      detected in cells inoculated with Ad41 treated with the highest free chlorine
      dose of 100 mg min/l. However, mRNA of adenovirus was detected in cells
      inoculated with virus that was untreated or exposed to a lower free chlorine dose
      of 1 mg min/l. These results suggest that mRNA detection by real-time RT-PCR is a
      sensitive and specific method to detect low levels of infectious adenoviruses in
      water and other environmental media within 1-3 days.

PMID- 15967238
TI  - Comparative evaluation of the VIDAS HIV DUO Ultra assay for combined detection of
      HIV-1 antigen and antibodies to HIV.
AB  - The aim of the study was to evaluate the performance of the combined antigen and
      antibody HIV screening assay VIDAS HIV DUO Ultra (BioMerieux, Marcy l'Etoile,
      France) in comparison with two other combined tests: the former version of the
      same test (VIDAS HIV DUO, BioMerieux) and the AxSYM HIV Ag/Ab Combo assay (Abbott
      Laboratories, Rungis, France). A prospective study was performed on serum
      specimens received on a routine basis for HIV testing: 1443 blood samples were
      tested with the three assays. Sensitivity was 100% for the three tests.
      Specificity assessed on repeated false-positive samples was 99.86, 99.03 and
      99.65% for VIDAS HIV DUO Ultra, VIDAS HIV DUO and AxSYM HIV Ag/Ab Combo,
      respectively. In addition, 14 seroconversion panels were tested with the VIDAS
      DUO Ultra and AxSYM HIV Ag/Ab Combo assays. For four of these panels, a positive
      signal was detected one blood sampling point earlier with the VIDAS DUO Ultra
      assay, corresponding to a higher sensitivity of the HIV antigen test. These
      results indicate that the VIDAS HIV DUO Ultra exhibits an improved specificity
      with comparison to the former version of this assay and an excellent sensitivity
      for early detection of HIV seroconversion.

PMID- 15967239
TI  - Using expert opinion to identify risk factors important to infectious salmon
      anemia (ISA) outbreaks on salmon farms in Maine, USA and New Brunswick, Canada.
AB  - Thirty industry or regulatory professionals, with extensive experience in the
      local infectious salmon-anemia (ISA) epidemic, were queried on their opinions
      regarding the spread and impact of ISA in Maine, USA and New Brunswick, Canada.
      Subjective probability-estimation techniques were used to elicit likelihood
      ratios (LR) for risk factors of potential relevance to the epidemic. Experts were
      asked to answer questions based on their direct and local experience with ISA,
      rather than through knowledge gained from scientific references or experience in
      other regions. The results found the strongest independent predictors of ISA
      infection to include (1) a site's proximity to other farms with clinically
      infected fish, (2) a previous history of ISA on the site, (3) whether a site
      fallows for a month or more between year classes and (4) whether the site employs
      harvest vessels practicing full containment of blood and stun water. The
      strongest predictors of ISA severity included (1) stocking density, (2) the
      length of time between infection and removal of infected fish, (3) whether fish
      are moved between pens (after infection) and (4) a farm's sea-lice
      (Lepeophtheirus salmonis) status. Experts believed that transmission of ISA virus
      during the local epidemic was influenced by proximity (spatial and temporal) to
      activities resulting in large-scale shedding of virus into a shared water column,
      and that severity of infection corresponded more to infected-fish removal
      practices and certain husbandry decisions. Personnel and equipment biosecurity
      measures were not seen as strong predictors of either infection or severity in
      this analysis, though their perceived level of importance was greater among
      government than industry experts.

PMID- 15967240
TI  - Evaluation of an antimicrobial resistance monitoring program for Campylobacter in
      poultry by simulation.
AB  - An ideal national resistance monitoring program should deliver a precise estimate
      of the resistance situation for a given combination of bacteria and antimicrobial
      at a low cost. To achieve this, decisions need to be made on the number of
      samples to be collected at each of different possible sampling points. Existing
      methods of sample size calculation can not be used to solve this problem, because
      sampling decisions do not only depend on the prevalence of resistance and
      sensitivity and specificity of resistance testing, but also on the prevalence of
      the bacteria, and test characteristics of isolation of these bacteria. Our aim
      was to develop a stochastic simulation model that optimized a national resistance
      monitoring program, taking multi-stage sampling, imperfect sensitivity and
      specificity of diagnostic tests, and cost-effectiveness considerations into
      account. The process of resistance testing of Campylobacter spp. isolated from
      cloacal swab samples from poultry was modeled using a Markov Chain Monte Carlo
      model. Different sampling scenarios on the number of flocks to be tested, the
      number of birds from each flock, and the number of campylobacter colonies
      submitted to susceptibility testing were evaluated regarding the precision of the
      resulting prevalence estimate. Precision of the prevalence estimate was defined
      as the absolute difference between apparent and true prevalence of resistance. A
      partial budget approach was utilized to find the most cost-effective combination
      of samples to obtain a defined precision of the prevalence estimate. For a
      sampling scenario testing 100 flocks, five birds per flock, and one campylobacter
      colony per sample, the median error of the prevalence estimate was 2.5%, and 95%
      of the simulations resulted in an error of 7% or less. When the total number of
      samples was kept constant, maximizing the number of flocks tested, and only
      testing one bird per flock resulted in the most precise prevalence estimate.
      Submitting more than one campylobacter colony to resistance testing did not
      improve the prevalence estimate. Partial budget analysis indicated that the most
      cost-effective strategy was testing of two birds per flock, and submitting one
      colony per sample to resistance testing.

PMID- 15967241
TI  - Sero-prevalence of avian influenza among broiler-breeder flocks in Jordan.
AB  - Thirty blood samples were collected randomly from each of the 38 breeder-broiler
      farms in Jordan. Serum samples were examined using indirect ELISA for specific
      antibodies to avian influenza virus. The overall true flock-level sero-prevalence
      of avian influenza was 71% (95% CI: 55,83). Positive flocks had 2-30 sero
      positive chickens and half of flocks had >20 sero-positive birds. The number of
      sero-positive flocks varied in the studied localities with more sero-positives in
      farms located within the migratory route of migratory wild fowl. The examined
      broiler-breeder flocks had no clinical signs, or noticeable decrease in egg
      production; mortalities were within the normal range (0.1-1%). The number of
      positive sera/flock correlated with flock size. There were a no significant
      (Pearsons r=0.21, p=0.21) correlation between positive flocks and age. A non
      pathogenic AI virus infects broiler-breeder farms in Jordan. Wild local and
      migrating birds might promote the further spread of this virus in Jordan and
      other countries.

PMID- 15967242
TI  - Antibody seroprevalences against peste des petits ruminants (PPR) virus in
      camels, cattle, goats and sheep in Ethiopia.
AB  - A questionnaire-survey data indicated that 26% of 276 farmers reported the
      presence of respiratory disease in their herds in 2001. The incidence was
      perceived as "high" in small ruminants and camels, but as "low" in cattle.
      Simultaneously, 2815 serum samples from camels (n=628), cattle (n=910), goats
      (n=442) and sheep (n=835) were tested. The peste des petits ruminants (PPR)
      antibody seroprevalence was 3% in camels, 9% in cattle, 9% in goats and 13% in
      sheep. The highest locality-specific seroprevalences were: camels 10%, cattle
      16%, goats 22% and sheep 23%. The animals had not been vaccinated against
      rinderpest or PPR. Antibody seroprevalences detected in camels, cattle, goats and
      sheep confirmed natural transmission of PPR virus under field conditions.

PMID- 15967243
TI  - Simulating the sensitivity of pooled-sample herd tests for fecal Salmonella in
      cattle.
AB  - Samples from livestock or food items are often submitted to microbiological
      analysis to determine whether or not the group (herd, flock or consignment) is
      shedding or is contaminated with a bacterial pathogen. This process is known as
      'herd testing' and has traditionally involved subjecting each sample to a test on
      an individual basis. Alternatively one or more pools can be formed by combining
      and mixing samples from individuals (animals or items) and then each pool is
      subjected to a test for the pathogen. I constructed a model to simulate herd
      level sensitivity of the individual-sample approach (HSe) and the herd-level
      sensitivity of the pooled-sample approach (HPSe) of tests for detecting pathogen.
      The two approaches are compared by calculating the relative sensitivity (RelHSe =
      HPSe/HSe). An assumption is that microbiological procedures had 100% specificity.
      The new model accounts for the potential for HPSe and RelHSe to be reduced by the
      dilution of pathogen that occurs when contaminated samples are blended with
      pathogen-free samples. Key inputs include a probability distribution describing
      the concentration of the pathogen of interest in samples, characteristics of the
      pooled-test protocol, and a 'test-dose-response curve' that quantifies the
      relationship between concentration of pathogen in the pool and the probability of
      detecting the target organism. The model also compares the per-herd cost of the
      pooled-sample and individual-sample approaches to herd testing. When applied to
      the example of Salmonella spp. in cattle feces it was shown that a reduction in
      the assumed prevalence of shedding can cause a substantial fall in HPSe and
      RelHSe. However, these outputs are much less sensitive to changes in prevalence
      when the number of samples per pool is high, or when the number of pools per herd
      test is high, or both. By manipulating the number of pools per herd and the
      number of samples per pool HPSe can be optimized to suit the range of values of
      true prevalence of shedding of Salmonella that are likely to be encountered in
      the field.

PMID- 15967244
TI  - A longitudinal study of growing pigs raised by smallholder farmers in the
      Philippines.
AB  - We conducted a longitudinal study to obtain baseline information about the health
      and growth of growing pigs raised by smallholder pig raisers in the Philippines,
      and to test constraints and opportunities to smallholder growing pig production
      that had been identified in a cross-sectional study [More, S.J., Lee, J.-A.L.M.,
      Lanada, E.B., Taveros, A.A., Cotiw-an, B.S., 1999. Weight-for-age of growing pigs
      raised by smallholder farmers in the Philippines. Prev. Vet. Med. 41, 151-169].
      Using monthly on-farm visits over 12-18 months at two sites, we collected data
      about 824 growing pigs raised in 115 separate herds. Weight-for-age (median value
      of 4.8 kg/month) was clustered strongly at the herd level, and the daily ration
      to growing pigs was substantially deficient (particularly in protein). Using
      repeated-measures and time-to-event analyses, we identified a range of animal-
      and herd-level variables associated with increased growth and health. These
      results confirm results from our earlier study, and suggest that improved
      nutrition and targeted extension on a range of management issues could be useful.

PMID- 15967245
TI  - A longitudinal study of sows and boars raised by smallholder farmers in the
      Philippines.
AB  - We conducted a longitudinal study to obtain baseline information about the health
      and productivity of sows and boars raised by smallholder-pig raisers in the
      Philippines, and test constraints and opportunities to smallholder-sow production
      that had been identified previously in a cross-sectional study [More, S.J., Lee,
      J.-A.L.M., Lanada, E.B., Taveros, A.A., Cotiw-an, B.S., 1999. Weight-for-age of
      growing pigs raised by smallholder farmers in the Philippines. Prev. Vet. Med.
      41, 151-169]. Over 12-18 months, we collected data during monthly on-farm visits
      about 213 sows raised in 119 herds at 2 sites and 32 boars in 31 herds at 1 site.
      Sow reproductive performance was low and boars were used only infrequently (an
      average of 0.9 services/month). Using repeated-measure analyses, we identified
      sow nutrition and piglet care (such as provision of creep feed and unrestricted
      access to the sow) as important husbandry issues associated with increased sow
      productivity.

PMID- 15967246
TI  - A longitudinal study of unweaned piglets raised by smallholder farmers in the
      Philippines.
AB  - We conducted a longitudinal study to obtain detailed baseline information about
      the health and productivity of unweaned piglets raised by smallholder pig raisers
      in the Philippines, and to identify constraints and opportunities to smallholder
      piglet production. At two sites in the Philippines, we collected data about 242
      litters from 173 sows in 102 herds during on-farm visits over 12-18 months.
      Preweaning mortality at the northern and southern sites was 17 and 9%,
      respectively. Of the piglet deaths at the northern site, 49% occurred within 24h
      of birth. Pig raisers used few of the recognised interventions known to reduce
      neonatal piglet mortality, although >50% of litters were given iron injections at
      the northern site and kept in a farrowing pen with a barrier at the southern
      site. Creep feeding was more common at the northern site but the nutritive value
      of the feeds given to piglets was low. We used repeated-measures and time-to
      event analyses. Our results suggest that targeted extension (addressing, in
      particular, management issues relating to neonatal piglets) can contribute to
      increased productivity of unweaned piglets.

PMID- 15967247
TI  - Simulating the spatial dynamics of foot and mouth disease outbreaks in feral pigs
      and livestock in Queensland, Australia, using a susceptible-infected-recovered
      cellular automata model.
AB  - We describe an approach to modelling the spatio-temporal spread of foot and mouth
      disease through feral animal and unfenced livestock populations. We used a
      susceptible-infected-recovered model, implemented in a cellular automata
      framework, to assess the spread of FMD across two regions of Queensland,
      Australia. Following a sensitivity analysis on the infectious states, scenario
      analyses were conducted using feral pigs only as the susceptible population, and
      then with the addition of livestock, and initiated in the wet season and in the
      dry season. The results indicate that, depending on the season the outbreak is
      initiated, and without the implementation of control measures, an outbreak of
      Foot and Mouth Disease around Winton could continue unchecked, while an outbreak
      around Cape York may die out naturally. The approach explicitly incorporates the
      spatial relationships between the populations through which the disease spreads
      and provides a framework by which the spread of disease outbreaks can be explored
      through varying the model parameters. It highlights the emergence and importance
      of spatio-temporal patterns, something that previous modelling of FMD in feral
      animal and unfenced livestock populations has lacked.

PMID- 15967248
TI  - Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer.
AB  - OBJECTIVES: A relation of prostate cancer risk with calcium, vitamin D and
      phosphorus has been suggested, but remains controversial. METHODS: A case-control
      study was conducted in Italy in 1991-2002. Cases were 1294 men with incident
      prostate cancer, and controls were 1451 men admitted to hospital for acute non
      neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence
      intervals (CI) were estimated using unconditional multiple logistic regression.
      RESULTS: Compared to the lowest one quintile of dietary calcium intake the OR was
      1.18 for the highest, 1.01 for an increment of 622 mg/day of calcium, and 1.29
      (95% CI 0.78-2.13) for 2000 mg/day or more of calcium. The OR of prostate cancer
      for the highest quintile of dietary intake of vitamin D and phosphorus were 1.33
      and 1.20 respectively. CONCLUSIONS: This study shows no material association of
      dietary intake of calcium, vitamin D and phosphorus with prostate cancer risk.

PMID- 15967249
TI  - Insulin-like growth factor 1, chromogranin A and prostate specific antigen serum
      levels in prostate cancer patients and controls.
AB  - OBJECTIVE: Insulin-like growth factor 1 (IGF-1) and chromogranin A (CGA) are
      currently discussed as supplemental serum markers for prostate cancer (PC)
      diagnosis. To address this issue we determined serum levels of IGF-1, CGA and PSA
      in men with newly diagnosed PC and controls. METHODS: A consecutive series of 156
      men (median age: 67 yrs) with newly diagnosed, untreated PC and 271 controls (69
      yrs) were recruited. The diagnosis of PC was made by transrectal ultrasound
      guided biopsies only. In controls, the presence of PC was excluded by digito
      rectal examination, serum prostate specific antigen (PSA) levels by using age
      specific reference values and-if indicated-by transrectal ultrasound guided 12
      core biopsies. Serum levels of IGF-1, CGA and PSA were compared between cases and
      controls and correlated to histopathological findings and age. RESULTS: Serum PSA
      levels were significantly higher in men with PC (49.6+/-13.9 ng/ml, mean+/
      standard error of the mean; median: 7.0 ng/ml) than in controls (2.6+/-0.2 ng/ml;
      median: 1.3 ng/ml) (p<0.001). In contrast, serum levels of IGF-1 (PC: 166+/-6.1
      ng/ml, median: 155 ng/ml; controls: 159+/-4.5 ng/ml, 153 ng/ml) and CGA (PC: 92+/
      7.4 U/l, median: 67 U/l; controls: 117+/-12.0 U/l; median: 74 U/l) were identical
      in both groups (p>0.05). Serum levels of IGF-1 and CGA revealed no correlation to
      serum PSA, Gleason score and number of positive biopsy cores. In the PC-cohort
      all three serum markers did not correlate with age. In controls, PSA (p=0.018)
      and CGA (p<0.001) correlated positively and IGF-1 (p<0.001) negatively with age.
      CONCLUSION: Our data suggest that quantification of IGF-1 and CGA-serum levels
      provides no useful information in the diagnosis of PC.

PMID- 15967250
TI  - PSA bouncing after short term androgen deprivation and 3D-conformal radiotherapy
      for localized prostate adenocarcinoma and the relationship with the kinetics of
      testosterone.
AB  - OBJECTIVES: To assess the factors effecting PSA bounce and to identify any
      possible relationship with biochemical control after 3-D conformal radiotherapy
      (3D-CRT) and total androgen deprivation (TAD) for prostate cancer by evaluating
      four previously described PSA bounce definitions. METHODS: Between January 1998
      and January 2001, 83 consecutive patients with clinically localized prostate
      cancer were treated by 3D-CRT with neoadjuvant 3 months and/or 6 months adjuvant
      TAD. All patients had a pretreatment PSA level, at least eight post-external beam
      radiotherapy (EBRT) PSA and testosterone levels and minimum two years of follow
      up. Total radiotherapy dose was 73.6 Gy at ICRU reference point. Four previous
      definitions of PSA bounce were used: Critz definition (>or=0.1 ng/mL), Cavanagh
      definition (>or=0.2 ng/mL), Hanlon definition (>or=0.4 ng/mL) and Rosser
      definition (>or=0.5 ng/mL) according to original methodology performed to report
      PSA bounce. Biochemical failure was defined in accordance with the ASTRO
      consensus guidelines. RESULTS: The median follow-up time was 40 months. PSA
      bounce was recorded as follows: Critz definition, 33 patients (40%); Cavanagh
      definition, 21 patients (25%); Hanlon definition, 11 patients (13%); and Rosser
      definition, 7 patients (8%). In multivariate analysis, pre-EBRT PSA level and the
      duration of TAD for Critz definition; age, pre-EBRT PSA and the duration of TAD
      for Cavanagh definition; age and duration of TAD for Hanlon definition; age and
      pre-biopsy PSA for Rosser definition were significant independent prognostic
      factors determining PSA bounce. A significant increase of mean testosterone level
      in bouncers was detected at the 6th-9th and 18th-21st months. PSA bounce did not
      predict for PSA failure in multivariate analysis. CONCLUSIONS: We observed no
      correlation between biochemical failure and PSA bounce. The longer duration of
      TAD and older age were found to be inversely proportional with PSA bouncing in
      this cohort. Notably, recovery of testosterone might cause PSA bouncing.

PMID- 15967251
TI  - Interindividual variation in distribution of extramural ganglion cells in the
      male pelvis: a semi-quantitative and immunohistochemical study concerning nerve
      sparing pelvic surgery.
AB  - OBJECTIVE: We examined distribution and numbers of extramural ganglion cells in
      the male pelvis, classifying them as sympathetic or parasympathetic. METHODS:
      Specimens were obtained from 14 formalin-fixed donated male cadavers. Semiserial
      sections were processed for histologic examination, and for immunohistochemistry
      using anti-tyrosine hydroxylase (TH) or anti-peptide histidine isoleucine (PHI).
      RESULTS: Like those along the sacral sympathetic trunk, most other pelvic
      ganglion cells were located in and along nerve components. Yet the ganglion cell
      clusters attached to pelvic viscera accounted for 22% to 38% of ganglion cells.
      These were seen at the dorsal aspect of the bladder, the bladder/prostate
      junction, the dorsal aspect of the seminal vesicle, and along the prostate, but
      not along the extrapelvic pudendal nerve, cavernous tissues including the penile
      hilum, the rhabdosphincter, retropubic fat or recto-urethral muscle. Two fold
      interindividual variation was seen for total ganglion cell number (3044 to 6522)
      in the pelvis. TH-positive and PHI-positive cells intermingled at various ratio
      in every ganglion cell cluster. Sympathetic TH-positive proportions tended to be
      site-specific. CONCLUSIONS: Pelvic autonomic cells exist not only in nerve
      components but also along viscera. Even nerve-sparing radical prostatectomy can
      compromise visceral ganglia. Simple classification of pelvic nerve components as
      sympathetic or parasympathetic would seem misleading given coexistence of both
      cell types in a ganglion.

PMID- 15967252
TI  - Cystectomy in patients with high risk superficial bladder tumors who fail
      intravesical BCG therapy: pre-cystectomy prostate involvement as a prognostic
      factor.
AB  - PURPOSE: To review understaging and outcome of patients who underwent radical
      cystectomy (RC) for high risk superficial bladder cancer after bacillus Calmette
      Guerin (BCG) failure. PATIENTS AND METHODS: We carried out a retrospective study
      of 62 cases in which RC was indicated for clinical stage Tis, Ta, T1 transitional
      cell bladder tumors that failed transurethral resection (TUR) and BCG treatment.
      We used BCG (81 mg/Connaught BCG) in patients with superficial grade 3 tumors and
      CIS. We considered BCG failure a high-grade recurrence at 3 months of the first
      BCG course or after 2 courses. RC indications, correlation between their clinical
      and pathological stage and the ensuing progress were analyzed. We assessed the
      existence of any pre-cystectomy clinical or pathological factor related to
      understaging and survival. RESULTS: RC was performed in 22 patients with
      carcinoma in situ (CIS) (35%), 7 with Ta (11,2%), 31 with T1 (50%), and 2 with Tx
      tumors (3%). All 62 but one were high-grade tumors (grade 3 and/or CIS). Tumor
      was clinically understaged with stages pT2 or greater on the RC specimen in 17
      patients (27%). The presence of tumor in the prostatic urethra at the moment of
      endoscopic staging before RC was the only factor associated with clinical
      understaging (p=0.003) and shorter survival (p<0.0002). Five-year disease
      specific survival rate was significantly lower in understaged (38%) as compared
      with not-understaged patients (90%) after a median follow-up of 40-months (range
      1-142) (p=0.006). Overall five-year disease-specific survival was 79%.
      CONCLUSIONS: RC should be performed prior to progression in high risk superficial
      tumors that fail after TUR and BCG. In patients with clinical and pathological
      nonmuscle invasive disease, RC provides an excellent disease-free survival. One
      third of patients with HRSBT who underwent RC after BCG failure were understaged
      and had a shorter survival. Tumor in the prostatic urethra at endoscopic staging
      was the only factor associated to understaging and shorter survival.

PMID- 15967253
TI  - Adjuvant and neoadjuvant chemotherapy in muscle invasive bladder cancer:
      literature review.
AB  - Radical cystectomy is the standard treatment for patients with clinically
      localized muscle invasive bladder cancer, providing a 5-year survival rate of
      approximately 50%. Failure to cure is often due to the presence of occult
      metastases beyond the margins of local therapy, indicating a need for eradication
      of micrometastatic disease with systemic treatment, in order to improve survival.
      Combined chemotherapy regimens, such as methotrexate-vinblastine-cisplatin (CMV),
      methotrexate-vinblastine-cisplatin-doxorubicin (M-VAC) and gemcitabine-cisplatin
      (GC) have already demonstrated their effectiveness in patients with advanced or
      metastatic disease and have been considered as appropriate regimens in the peri
      operative setting. Large randomized studies with a prolonged follow-up have been
      able to confirm a modest survival benefit with neoadjuvant therapy. A recent meta
      analysis, including all previous reported randomized trials, concluded that
      neoadjuvant chemotherapy administration provides a significant survival benefit
      and can be administered without adverse outcomes resulting from delayed local
      therapy. Adjuvant chemotherapy trials, although promising, have failed to show
      statistically improved survival, mostly due to small sample sizes and absent or
      inconclusive data on overall survival. A multi-center randomized-controlled trial
      is currently ongoing, in order to elucidate the role of post-operative
      chemotherapy administration.

PMID- 15967254
TI  - Urinary levels of soluble e-cadherin in the detection of transitional cell
      carcinoma of the urinary bladder.
AB  - OBJECTIVE: To test the hypothesis that elevated urinary levels of soluble E
      cadherin (sE-cadherin) would aid in the detection of transitional cell carcinoma
      (TCC) of the urinary bladder. METHODS: We performed sE-cadherin staining of one
      murine (MBT2) and four human (RT4, 5637, T24, and TCCSUP) bladder cancer cell
      lines. sE-cadherin levels were also determined in voided urine of 188 consecutive
      subjects at risk for TCC recurrence, 31 patients with other uro-pathologic
      conditions, and 10 healthy subjects using a commercially-available ELISA kit. sE
      cadherin was analyzed continuously and categorically on the basis of its median
      distribution. RESULTS: Moderately and poorly differentiated bladder cancer cell
      lines had decreased cellular E-cadherin expression, whereas RT4, a well
      differentiated cell line, had preserved expression. All cell lines had measurable
      sE-cadherin levels in their conditioned media. The area under the ROC curve of sE
      cadherin for the detection of TCC was 0.719 (95%CI, 0.637-0.801; p<0.001). Higher
      levels of sE-cadherin were associated with positive cytology results (p=0.012)
      and muscle invasive tumor stage (p=0.009). Urinary sE-cadherin was more
      sensitive, but less specific than urinary cytology for the detection of bladder
      TCC. In a multivariable logistic regression analysis, higher sE-cadherin and
      positive cytology were both associated with an increased risk of bladder TCC
      (p=0.048 and p<0.001, respectively). Combination of cytology and sE-cadherin
      allowed categorization of patients into three significantly different risk groups
      for bladder cancer. Adjustment of sE-cadherin for urinary creatinine levels did
      not affect any of the outcomes. CONCLUSIONS: Urinary level of sE-cadherin may add
      information to cytology in the detection of bladder TCC.

PMID- 15967255
TI  - Prognostic factors and survival after pulmonary resection of metastatic renal
      cell carcinoma.
AB  - OBJECTIVE: Pulmonary metastasectomy as well as immunotherapy have reproducible,
      albeit limited efficacy in advanced renal cell carcinoma (RCC). We examined
      whether metastasectomy improved overall survival compared with results of
      immunotherapy. METHODS: Between 1975 and 2003, 64 patients (41 men, 23 women)
      underwent pulmonary resection of metastatic RCC. Only patients who met the
      criteria for potentially curative operation, that means, control of primary
      tumor, ability to resect metastatic disease and no other extrapulmonary
      metastases, were included. RESULTS: The overall 5-year survival was 33.4% (median
      survival: 39.2 months). A significant longer survival was observed using
      multivariate analysis in patients with complete pulmonary resection (R0), with a
      5-year survival of 39.9% and a median survival of 46.6 months in correlation to
      patients with incomplete resection (5-year survival 0%, median survival 13.3
      months). In multivariate analysis patients with synchronous metastases had a
      significant worse prognosis in correlation to patients with metachronous
      metastases. The 5-year survival of curative resected patients with metachronous
      metastases was 43.7% versus 0% for synchronous metastases, respectively. In
      patients with solitary metastasis and R0 resection, we observed a 5-year survival
      of 49%, whereas the rate was 23% in patients with more than a single metastasis.
      When establishing prognostic groups as suggested by the International Registry
      based on the risk factors disease-free interval, number of metastasis and
      complete resection the group with the best prognosis showed a 5-year survival of
      52% (median survival 75.2 months). CONCLUSION: Metastasectomy nowadays is the
      best treatment option in cases with technical resectable metastases with as much
      as possible good prognostic factors (metachronous metastases with long DFI,
      number up to 6 metastases).

PMID- 15967256
TI  - Morbidity of laparoscopic extraperitoneal versus transperitoneal radical
      prostatectomy verus open retropubic radical prostatectomy.
AB  - OBJECTIVE: Morbidity and postoperative pain after extraperitoneal (E-LRPE) and
      transperitoneal (T-LRPE) laparoscopic radical prostatectomy was compared to open
      extraperitoneal radical prostatectomy (O-RPE). MATERIAL AND METHODS: Between
      January 2002 and October 2003, we evaluated 41 E-LRPE, 39 T-LRPE and 41 O-RPE
      prospectively. All operations were performed as standard procedures by the same
      group of surgeons and perioperative results and complications were evaluated.
      Pain management was performed with tramadol 50-100 mg on demand, and no other
      form of anaesthesia was given. Postoperative pain was assessed daily in all
      patients quantifying analgesic requirement and evaluation of Visual Analogue
      Scale (VAS). All patients had at least a 12 month follow-up. RESULTS: Mean age,
      prostate volume, PSA and Gleason score were comparable between all three groups
      (p>0.05). Mean blood loss was lower with laparoscopy (189+/-140 and 290+/-254
      ml), as compared to 385+/-410 ml for O-RPE (p=0.002). However, mean operating
      times were significantly longer in L-TRPE (279+/-70 min) as compared to E-LRPE
      (217+/-51 min) and O-RPE (195+/-72 min) (p<0.001), but E-LRPE and O-RPE showed no
      statistical difference (p=0.1143). Average VAS score on the 1st and 5th
      postoperative day for E-LRPE versus T-LRPE versus O-RPE was 4.9+/-1.0 versus
      7.8+/-1.5 versus 5.8+/-1.9 and 1.6+/-0.9 versus 2.3+/-1.2 versus 2.3+/-0.9
      respectively, which was significant lower (p=0.02) between E-LRPE versus T-LRPE
      (p<0.001) and O-RPE (p=0.008), but equal (p=0.655) between T-LRPE and O-RPE since
      postoperative day 3. Mean tramadol analgesic consumption within the first
      postoperative week was 290 versus 490 versus 300 mg respectively, which was
      statistical different between E-LRPE and T-LRPE (p<0.001), O-RPE and T-LRPE
      (p<0.001), but not between E-LRPE and O-RPE (p=0.550). Statistical analysis
      revealed a strong correlation of urinary leakage with increased postoperative
      pain (p=0.029) in all groups, especially for T-LRPE (p=0.007). Likewise,
      increased operating times (>240 min) were associated with increased post
      operative pain (p=0.049). Full continence defined as no pads at one year was
      achieved in 36/41 (88%, E-LRPE) versus 33/39 (85%, T-LRPE) versus 33/41 (81%, O
      RPE), respectively (p=0.2). CONCLUSION: E-LRPE resulted in a significant
      subjective (VAS Score, p<0.001) and objective (analgetic consumption, p<0.001)
      pain reduction compared to T-LRPE, but only in VAS Score compared to O-RPE
      (p=0.008). Analgetic consumption during first postoperative week was equal in E
      LRPE (290 mg) and O-RPE (300 mg) (p=0.550). Shorter operating times, lower
      urinary leakage rates, lower stricture rates and lower blood loss in E-LRPE
      compared to T-LRPE are mainly explained due to the long learning curve in LRPE,
      which we did not overcome yet, and not due to the approach (extraperitoneal
      versus transperitoneal).

PMID- 15967257
TI  - Retroperitoneoscopic donor nephrectomy: a retrospective, non-randomized
      comparison of early complications, donor and recipient outcome with the standard
      open approach.
AB  - OBJECTIVES: We retrospectively performed a comparative analysis of
      retroperitoneoscopic and open donor nephrectomy in terms of donor complications,
      as well as recipient complications and functional graft outcome. METHODS: A total
      of 134 donor nephrectomies including 69 open (ODN) and 65 retroperitoneoscopic
      (RDN) nephrectomies was analyzed retrospectively. Both groups were comparable in
      terms of age, body mass index (BMI), operating time (OPT), warm ischemia time
      (WIT) and blood loss. RESULTS: There were no statistically significant
      differences with respect to recipient outcome, mean values for age, BMI, OPT and
      cold ischemia time (CIT). The overall donor complication rate did not differ.
      Early functional graft follow-up showed significant differences in 24 h-urine
      output between the two groups (p<0.001), but serum creatinine was comparable
      after 7, 30, 180 and 365 days. The early rejection rate in the recipients was
      similar in the two groups. CONCLUSION: Retroperitoneoscopic donor nephrectomy
      (RDN) provides comparable perioperative features, such as operating time, warm
      ischemia time (WIT) and overall complication rate to the open donor nephrectomy
      (ODN). Additionally, it has no negative impact on recipients' operating time,
      graft ischemia and early graft function.

PMID- 15967258
TI  - Urological retroperitoneoscopic surgery for patients with prior intra-abdominal
      surgery.
AB  - OBJECTIVE: To determine whether previous intra-abdominal surgery is associated
      with surgical outcome in patients undergoing urological retroperitoneoscopic
      surgery. PATIENTS AND METHODS: One hundred seventeen cases of urological
      retroperitoneoscopic surgery, including 78 cases of retroperitoneoscopic radical
      nephrectomy (RN) for localized renal tumor and 39 cases of retroperitoneoscope
      assisted radical nephroureterectomy (RNU) for upper urinary tract cancer, were
      evaluated. Thirty (38.5%) of the 78 patients who underwent RN and 13 (33.3%) of
      the 39 patients who underwent RNU had a history of intra-abdominal surgery. The
      patients were divided into two groups: those who had undergone prior intra
      abdominal surgery (OP+) and those who had not (OP-). Patients' backgrounds,
      degree of surgical invasiveness, and period of convalescence were compared
      between the OP+ and OP- groups. RESULTS: There was no significant difference
      between the OP+ and OP- groups in terms of background, surgical invasiveness or
      convalescence, except for age in the patients who had undergone RN. Complications
      in the studied cases were unrelated to any history of intra-abdominal surgery.
      CONCLUSION: Previous intra-abdominal surgery is not associated with a negative
      outcome of urological retroperitoneoscopic surgery in patients with localized
      renal tumors and those with upper urinary tract cancer.

PMID- 15967259
TI  - Comparison of symptom severity and treatment response in patients with
      incontinent and continent overactive bladder.
AB  - PURPOSE: Two thirds of patients with overactive bladder (OAB) are continent, but
      our knowledge on the treatment of the syndrome is largely based on studies with
      incontinent patients. Therefore, we have explored baseline symptoms and treatment
      responses to tolterodine in continent relative to incontinent OAB patients.
      MATERIALS AND METHODS: Data from an open-label, observational study involving
      3824 patients with OAB symptoms were analyzed for baseline symptoms and
      alterations thereof upon a 9 months treatment with 4 mg q.d. tolterodine ER.
      RESULTS: Baseline symptoms (number of urgency episodes, total urination
      frequency, daytime frequency, nocturia, and three scales of OAB severity) were
      similar in 1147 continent and 2571 incontinent patients, the latter having 4.8+/
      3.7 incontinence episodes per 24 h. Tolterodine ER-induced reduction of OAB
      symptoms was very similar in both groups of patients. CONCLUSIONS: The severity
      of OAB in continent patients can be similar to that in incontinent ones. Symptom
      improvement upon treatment with tolterodine ER is very similar in both groups. We
      propose that continent patients may similarly deserve treatment with a muscarinic
      receptor antagonist as incontinent ones.

PMID- 15967260
TI  - Urethral sensitivity in incontinent women.
AB  - OBJECTIVES: The aim of this study was to ascertain whether frequent voiding and
      urge incontinence are associated with supersensitivity to electrical stimulation
      in the posterior urethra. METHODS: Current perception thresholds (CPT) were
      tested at four stimulus frequencies (1, 3, 20, and 100 Hz; duration 0.5 ms) using
      a square-wave constant current electrical stimulator connected to ring electrodes
      on a urethral catheter. The strength of the current at the first tingling
      sensation was regarded as the CPT. CPT analysis and cystometry were performed on
      61 women (ages 28-89 years). RESULTS: CPTs were significantly higher at lower
      than at elevated stimulus frequencies, and they were also generally higher in old
      than in younger patients. Seven women repeated the CPT test after two months, and
      the thresholds were unchanged. There were no significant differences in
      sensitivity between patient groups with stress incontinence, urge, or mixed
      symptoms. Moreover, CPT was not significantly related to bladder volume at first
      sensation of filling. CONCLUSION: Measuring CPT is an easy and reproducible
      method of testing urethral sensibility, but our results do not support the
      suspicion that urethral hypersensitivity is involved in increased voiding
      frequency and urge incontinence.

PMID- 15967261
TI  - Augmentation phalloplasty surgery for penile dysmorphophobia in young adults:
      considerations regarding patient selection, outcome evaluation and techniques
      applied.
AB  - OBJECTIVES: To report on the efficacy and safety of augmentation phalloplasty
      procedures in physically normal young men, to introduce a patient selection and
      outcome evaluation questionnaire as well as, to propose a surgical technique
      modification. METHODS: Eleven (11) out of 28 psychosomatically normal men (25-35
      years) who presented complaining of penile dysmorphophobia (subjective perception
      of small penis), were subjected to: (a) penile lengthening (suprapubic skin
      advancement--ligamentolysis): n=5, (b) penile lengthening and shaft thickening
      (free dermal-fat graft shaft coverage): n=3 and (c) panniculectomy--suprapubic
      lipectomy and penile lengthening: n=2. A self administered questionnaire was
      employed in order to facilitate selection of the patients qualifying for the
      operation as well as to evaluate the outcome. In addition, a technical
      modification regarding dermal-fat graft handling was applied. RESULTS: The
      postoperative course was uneventful with minor complications. The mean penile
      length gain (flaccid--stretched penis) was 1.6 cm (1-2.3 cm) [p=0.0014], the mean
      circumference gain was 2.3 cm [p=0.003] at the base and 2.6 cm [p=0.0012]
      subcoronaly. Significant (20%-53%) [p<0.0001] sexual self-esteem and functioning
      improvement was reported by the majority (91%) of patients. CONCLUSIONS: Although
      penile size alteration was not spectacular or satisfying the patients' "great"
      expectations, the substantially uneventful clinical course coupled with the
      significant improvement in sexual self-esteem and function and the highly
      accepted outcome by the patients, render augmentation phalloplasty reasonable
      treatment modality for the management of strictly selected and thoroughly
      informed young adults who suffer from penile dysmorphophobia.

PMID- 15967262
TI  - The surgical treatment of Peyronie's disease: replacement of plaque by free
      autograft of buccal mucosa.
AB  - OBJECTIVES: The aim of this work was the evaluation of clinical results of the
      use of buccal mucosa for replacement of Peyronie's disease plaque. PATIENTS AND
      METHODS: Twenty-six patients with Peyronie's disease were under observation. All
      the patients underwent the following investigations before and periodically
      within 3 years after the treatment: International Index of Erectile Function
      (IIEF-5), manual examination of plaque, autophotography of erect penis,
      conventional and power color Doppler sonography of penis, Peno-Brachial Index
      (PBI) before and its increase (IPBI) after the intracavernous injection of
      papaverin, Peak Systolic Velocity (PSV), end diastolic velocity (EDV), Resistance
      Index (RI), Sexual Encounter Profile questions (SEP-2 and SEP-3), measurements of
      penile length and curvature angle in the phase of rigidity. After stabilization
      in plaque's development (mean time 2.0+/-0.1 years) the patients underwent a
      surgery by means of excision of plaque and its replacement by free autograft of
      buccal mucosa. RESULTS: After the surgical treatment (with mean follow up
      observation of 3.2+/-0.1 years) in 24 patients out of 26 (92.3%) the complete
      straightening of penis occurred, in two (7.7%) cases a residual curvature (<10
      degrees) remained, in four patients (15.4%) the shortening of penis (by 1cm) and
      in two patients (7.7%) a partial reduction of erectile power were observed.
      CONCLUSION: Buccal mucosa showed high properties of adaptation and
      revascularization, good anatomical and functional clinical results by replacement
      of indurative plaque, it kept a stable elasticity without shrinkage; the method
      is simple and can be recommended for wide use in clinics for surgical treatment
      of Peyronie's disease.

PMID- 15967263
TI  - Sildenafil non-responders: haemodynamic and morphometric studies.
AB  - OBJECTIVES: Most of the available data on efficacy for sildenafil are based on a
      questionnaire and erectile dysfunction (ED) is classified with minor or severe
      organic factors. To better select sildenafil responders and non-responders, we
      have conducted a haemodynamic and morphometric study in sildenafil non
      responders. METHODS: Thirty patients with ED aged from 28 to 74 years-old did not
      respond to 8 attempts of 100 mg of sildenafil. They underwent hormonal
      measurements, intracavernous injection (ICI 20 microg PgE1) followed by Doppler
      examination and cavernosometry. A penile biopsy was performed under local
      anesthesia. A quantification of the cavernous smooth muscle (SMC) was performed
      with a computerized image analysis after staining with actin anti-actin. RESULTS:
      Twenty-eight patients had a very poor ICI response. Five patients were diabetic
      and 2 had low testosterone level. Eight patients had arterial lesions, 15 had
      venous leak and 5 both lesions. They all had reduction of SMC (<35%). No
      biological and vascular abnormality was observed in two patients. They had a
      percentage of SMC of 38% and 42%. No complication was observed with the penile
      biopsy. CONCLUSIONS: Severe vascular lesions and atrophy of SMC are mainly
      observed in sildenafil non-responders. The age, diabetes and low testosterone
      level seem not to be related with the failures.

PMID- 15967264
TI  - Luminal nitric oxide in ileal reservoirs for continent cutaneous diversion or
      orthotopic bladder reconstruction.
AB  - OBJECTIVES: To measure mucosal inflammation as reflected in nitric oxide (NO)
      production in ileal reservoirs for the storage of urine and to correlate it with
      the growth of bacteria as well as CRP. METHODS: Intraluminal gas NO
      concentrations were determined using the chemoluminescence technique in 25
      patients with continent cutaneous ileal reservoirs (Kock pouch) and 12 patients
      with orthotopic bladders (hemi-Kock or T-pouch). NO concentrations were
      determined in both intestinal reservoir gas and silicon catheter balloon gas.
      Urinary culture and blood CRP determinations were performed. RESULTS: NO
      concentrations in reservoir gas were higher than in silicon catheter balloons.
      Bacteriuria was associated with approximately 20 times higher NO concentrations
      than sterile urine. NO concentrations did not differ between continent cutaneous
      reservoirs or orthotopic bladders when due attention was paid to variance in the
      rate of bacteriuria. Elevated CRP was associated with higher NO concentrations.
      Bacteriuria with acinetobacter, enterococci and pseudomonas appeared to cause
      comparatively lower NO concentrations. The inflammatory response of reservoir
      walls to bacteriuria did not decrease with time. CONCLUSIONS: Urine in itself
      causes much less intestinal wall inflammation than bacteriuria, as reflected in
      NO production. High CRP values are associated with high NO concentrations. The
      inflammatory response varies with the bacterial specimens.

PMID- 15967265
TI  - The use of telemetry technology to test the proerectile effect of melanotan-II
      (MT-II) in conscious rats.
AB  - OBJECTIVE: The aim of this study is to demonstrate that monitoring, by means of
      telemetry technology, the increases in intracavernosal pressure (ICP) in freely
      moving rats using melanotan-II (MT-II) as a proerectile inducer compound is a
      relevant experimental model to investigate the effects of pharmacological agents
      on erection. METHODS: Adult rats were implanted in the corpus cavernosum with a
      pressure sensor which permitted telemetric monitoring of ICP in freely moving
      animals following MT-II (0.1, 0.3 and 1 mg/kg) or saline i.v. injections. ICP was
      also measured after MT-II (0.1, 0.3 or 1 mg/kg) or saline i.v. delivery in
      anesthetized rats. RESULTS: In conscious rats, MT-II (1 mg/kg) significantly
      increased overall erectile activity compared to saline. In anesthetized rats, MT
      II-induced increase in overall erectile activity was not statistically
      significant but displayed a similar pattern. CONCLUSIONS: The use of telemetry
      technology allowed to collect quantifiable and reliable data regarding the
      proerectile activity of MT-II in physiological conditions. The telemetry model
      appears suitable for investigating the potential inducer proerectile properties
      of pharmacological agents.

PMID- 15967267
TI  - The distribution of sensory fibers immunoreactive for the TRPV1 (capsaicin)
      receptor in the human prostate.
AB  - OBJECTIVES: To determine the distribution of sensory fibers immunoreactive to the
      pain receptor TRPV1 in the human prostate. METHODS: Eight prostates were
      harvested from cadaver transplant donors and immediately immersion fixed.
      Longitudinal and transverse 20 microm sections were cut on a cryostat and
      immunoreacted with two anti-human TPRV1 antibodies. RESULTS: TRPV1-immunoreactive
      nerve fibers were distributed throughout the prostatic urethral mucosa,
      verumontanum, ejaculatory ducts and periurethral prostatic acini. In the urethral
      mucosa, TRPV1-immunoreactive fibers penetrated the epithelial layer up to its
      surface. In the transitional and peripheral zones of the gland no TRPV1
      immunoreactive nerve fibers were detected. CONCLUSIONS: The existence of a rich
      TRPV1 sensory innervation in the human prostate may open new therapeutic
      perspectives for the treatment of pain in patients with chronic prostatitis
      (Chronic Pelvic Pain Syndrome).

PMID- 15967266
TI  - Virus specific immune responses after human neoadjuvant adenovirus-mediated
      suicide gene therapy for prostate cancer.
AB  - PURPOSE: Neoadjuvant gene therapy potentially improves the outcome of primary
      treatment of prostate cancer by radical prostatectomy in patients with high risk
      of recurrence. We conducted a Phase I escalating dose study with a replication
      defective adenovirus expressing the herpes simplex virus-thymidine kinase gene
      (Adv-HSV-tk vector). The primary end point was toxicity, while the evaluation of
      the patients' cellular and humoral immune responses served as a secondary
      endpoint. MATERIAL AND METHODS: The Adv-HSV-tk vector was injected into the
      prostate in two doses (2x10(10) to 2x10(11) viral particles), followed by
      ganciclovir twice daily for 14 days and retropubic radical prostatectomy on day
      21. Adenovirus-specific neutralizing, IgG and IgA antibodies were evaluated.
      Peripheral blood mononuclear cells (PBMC) were stimulated by Adv-HSV-tk and
      analysed for IFN-gamma production and 3H-thymidine incorporation. Prostate
      specimens were immunostained for B (CD20+) and for T (CD3+) lymphocytes. RESULTS:
      Toxicity was minor in all 8 patients treated. In the prostate, no virus related
      cytopathic effect could be observed. Dose-dependent infiltration of T and B
      lymphocytes in the whole prostate and in tumor areas was observed. Boosting of
      adenovirus-specific antibody responses was observed in 7 patients, and an
      increased adenovirus-specific PBMC proliferation and IFN-gamma production was
      seen after Adv-HSV-tk stimulation. CONCLUSION: Neo-adjuvant adenovirus-mediated
      cytotoxic gene therapy prior to prostatectomy for prostate cancer is feasible and
      safe in an outpatient setting for intraprostatic vector doses up to 2x10(11)
      viral particles. Activation of the immune system was observed. Application of
      higher vector doses may be considered.

PMID- 15967269
TI  - Re: Ebert T, Jockenhovel F, Morales A, Shabsigh R. The current status of therapy
      for symptomatic late onset hypogonadism with transdermal testosterone gel. Eur
      Urol 2005;47:137-46.

PMID- 15967270
TI  - Re: Bryan NP, Chapple CR. Frequency volume charts in the assessment and
      evaluation of treatment: how should we use them? Eur Urol 2004;46:636-40.

PMID- 15967274
TI  - Occurrence and fate of pharmaceutically active compounds in the environment, a
      case study: Hoje River in Sweden.
AB  - Pharmaceutically active compounds (PhACs) in the environment lately have been
      acknowledged to constitute a health risk for humans and terrestrial and aquatic
      ecosystems. Human and veterinary applications are the main sources of PhACs in
      the environment and the major pathways are excretion and discharge to the
      environment through sewage treatment plants (STPs). In this study, the occurrence
      and fate of selected human PhACs belonging to different therapeutic classes (non
      steroidal anti-inflammatory drugs, lipid regulators, anti-epileptics, antibiotics
      and beta-blockers) were investigated in a small river in the very south of
      Sweden. The objectives of the study were to evaluate the impact of a high and
      rather constant load in sewage influent on downstream concentrations and whether
      substances that are metabolized to a high degree in humans also show a low
      persistency in a natural aquatic environment. Water samples were collected from
      the influent and effluent of the STP, in a series of dammed reservoirs leading to
      discharge into the Hoje River in Sweden, and at several locations in the river
      downstream of the outfall. After enrichment by solid-phase extraction, the
      compounds were analyzed using GC-MS (methylated derivatives) or LC-MS/MS. In
      addition to the targeted pharmaceuticals, GC-MS analysis of the samples revealed
      the presence of other sewage-related pollutants (triclosan, caffeine, flame
      retardants, antioxidants) and these results where included for comparison.
      Removal efficiencies were calculated in the STP and found to display a wide range
      with numerous species surviving treatment at greater than half their influent
      concentrations, including diclofenac, the anti-epileptic carbamazepine, a beta
      blocker (propanolol), and antibiotics trimetoprim and sulfamethoxazole. Low
      removals were also observed for Tris(2-chloroisopropyl)phosphate (flame
      retardant), BHT-aldehyde (oxidation product of BHT) and synthetic musk (HHCB).
      The concentrations of chloride (Cl(-)) and boron (B) were used as natural inert
      tracers to estimate the relative extent of dilution of PhACs measured in the
      effluent of the STP on concentrations measured further downstream. Based on
      spatial trends of concentrations (recalculated to reflect a hypothetical scenario
      with no dilution), ibuprofen, ketoprofen, naproxen and dicofenac were shown to be
      subject to significant abiotic or biotic transformations or physical
      sequestration in the river. The beta-blockers atenolol, metoprolol and
      propanolol, the antibiotics trimetoprim and sulfametoxazole, and carbamazepine
      demonstrated a high degree of persistence. Fluctuations in the concentration of
      carbamazepine and gemfibrozil were observed along the series of reservoirs and
      within the river and are hypothesized to be due to release of parent compound
      from glucuronides. Several of the investigated substances (metaprolol, propanolol
      and carbamazepin) that exhibit low excretion rates as parent compounds
      demonstrate a surprising persistence in the aquatic environment. It is concluded
      that pharmaceutical substances with a high metabolic rate in humans (low
      excretion rate) do not necessarily induce a short lifetime in aquatic
      environments. Results from this study emphasize the need for a broader view on
      the concept of persistence that accounts for loading rates, in addition to
      removal mechanisms (e.g., transformation, volatility and physical sequestration
      by solids), under a variety of spatial and temporal scales.

PMID- 15967275
TI  - Identification of the pharmaceuticals for human use contaminating the Italian
      aquatic environment.
AB  - A predictive approach seems useful to identify pharmaceuticals in the environment
      and give an idea of overall levels of contamination, so as to restrict monitoring
      to those molecules most likely to be contaminants. We propose an approach based
      on two parts. The first is to rank the molecules according to the predicted
      environmental loads; the second is to refine the list by analysing the
      pharmaceuticals in sewage treatment plants (STPs) and comparing the
      concentrations with levels previously measured in surface water. This approach
      identified a restricted group of priority pollutants (ofloxacin, furosemide,
      atenolol, hydrochlorothiazide, carbamazepine, ibuprofen, spiramycin, bezafibrate,
      erythromycin, lincomycin and clarithromycin) in the aquatic environment in Italy,
      for further studies and monitoring.

PMID- 15967276
TI  - Contribution of effluents from hospitals and private households to the total
      loads of diclofenac and carbamazepine in municipal sewage effluents--modeling
      versus measurements.
AB  - The anti-epileptic drug carbamazepine and the non-steroidal anti-inflammatory
      drug diclofenac are frequently found as residues in the aquatic environment and
      also in samples of ground and drinking water. For both compounds, their loads
      occurring in the effluents from a military hospital and in the combined
      (household and hospital) sewage of a sewage pumping station (SPS) and a large
      municipal sewage treatment plant (STP) were predicted and measured within a field
      trial by collecting and analyzing defined composite samples over a time period of
      1 week. The use of pharmacokinetic data and precise information on the
      administration of the individual medicinal formulation was found to be essential
      for the validity of the predicted data. The measured data confirmed the validity
      of the predicted loads with recoveries between 63 and 102% for carbamazepine and
      around 35% for diclofenac in the hospital wastewater. A comparison of the weekly
      loads predicted and measured in the influents and effluents of a STP in Berlin
      (Germany) yielded a very low removal rate for diclofenac (less than 15%) and a
      removal rate of up to 40% for carbamazepine. In total, 2.0 kg of carbamazepine
      per week (105 kg/a) and 4.4 kg of diclofenac per week (226 kg/a) were discharged
      into Berlin's surface water by the municipal STP, which treats both household
      sewage from approximately one million inhabitants and large amounts of hospital
      effluents (approximately 12,060 hospital beds).

PMID- 15967277
TI  - Electrochemical determination of pharmaceuticals in spiked water samples.
AB  - The electrochemical behaviour of acidic and neutral pharmaceutical active
      compounds (PhACs) was studied by cyclic voltammetry and pulse voltammetric
      techniques on mercury, carbon nanotube paste, carbon paste and gold electrodes.
      The best results, in terms of sensitivity, linearity range and detection limits,
      were obtained by differential pulse voltammetry (DPV) for ofloxacin (LOD 5.2
      microM), differential pulse polarography (DPP) for clofibric acid (LOD 4.7
      microM) and normal pulse voltammetry (NPV) for diclofenac (LOD 0.8 microM) and
      propranolol (LOD 0.5 microM). An enrichment step of approximately two orders of
      magnitude was performed by a solid-phase extraction procedure (SPE) in order to
      concentrate the samples. The developed method was optimized and tested on spiked
      river water samples.

PMID- 15967278
TI  - Application of methods for assessing the geno- and cytotoxicity of Triclosan to
      C. ehrenbergii.
AB  - The toxic effects of Triclosan (2,4,4'-trichloro-2'-hydroxydiphenyl ether) on
      morphology and sexual and asexual reproduction of C. ehrenbergii were examined.
      In addition, the genotoxic effects of Triclosan were evaluated on the same alga
      using the microgel electrophoresis test, also-called Comet assay. Increasing
      Triclosan concentrations in the range 0.125-5 mg L(-1) did not affect size and
      shape of the cells but had relevant effects on both chloroplast morphology and
      dimension. Triclosan inhibited the vegetative growth of C. ehrenbergii at 0.5 mg
      L(-1). The effects on sexual reproduction indicate that the number of C.
      ehrenbergii zygospores was significantly reduced by the application of 0.937 mg
      L(-1). The Comet assay showed that Triclosan treatments led to a dose-dependent
      DNA damage of C. ehrenbergii; 0.25 mg L(-1)caused significant genotoxic effects
      and higher concentrations irreversibly altered the DNA strands. These results
      suggest that C. ehrenbergii could represent a useful organism to evaluate the
      whole toxicity of pharmaceuticals and personal care products (PPCPs), giving
      valuable information for a risk assessment.

PMID- 15967279
TI  - Toxicity of the antimicrobial oxytetracycline to soil organisms in a multi
      species-soil system (MS.3) and influence of manure co-addition.
AB  - The effects of oxytetracycline (OTC) on soil organisms have been studied using a
      multi-species-soil system (MS.3). Oxytetracycline concentrations of 0.01 mg/kg, 1
      mg/kg and 100 mg/kg soil were added to the 20 cm top arable soil layer, with and
      without horse/cow manure (0.15 g organic N/kg soil) co-addition. No mortality was
      observed for Eisenia foetida S. but significant effects on soil microbial
      enzymatic activities (phosphatase, dehydrogenase) were observed. The effects on
      soil microorganism were observed earlier but then recovered in systems with
      manure co-addition. More important, OTC related plant inhibition was observed in
      the manured but not in the non-manured systems. Oxytetracycline reached 0.19 and
      1.85 mg/l in the leachate of the soil spiked with 1 and 100 mg OTC/kg,
      respectively and 0.05 and 1.14 mg/l for the same OTC concentrations in the
      manured systems. The results confirm that manure can modify both the fate and the
      effects of OTC and that the multi-species-soil systems can reproduce the
      conditions for a realistic effect estimation of veterinary medicines.

PMID- 15967280
TI  - Antibiotic removal from wastewaters: the ozonation of amoxicillin.
AB  - The presence of amoxicillin, a widely used antibiotic, has been documented in
      Sewage Treatment Plant (STP) effluents. As for other pharmaceuticals, ozonation
      is proposed as a process for its abatement from these effluents. The results of
      ozonation experiments on amoxicillin-containing aqueous solutions indicate that
      ozone attack is mainly directed towards the phenolic ring of the studied molecule
      leading to the formation of hydroxyderivative intermediates. No direct evidences
      of attack on sulfur atom with sulfoxide formation are found. A kinetic
      investigation is carried out allowing the assessment of the kinetics of direct
      ozone attack and that of OH radicals to amoxicillin.

PMID- 15967281
TI  - Adsorption and degradation of enrofloxacin, a veterinary antibiotic on natural
      zeolite.
AB  - The adsorption of enrofloxacin, a veterinary antibiotic onto natural zeolite and
      further decontamination of zeolite was investigated in the present study. In the
      first part of the study, the effects of pH, temperature, and presence of ammonium
      ion on the adsorption process were examined and evaluated on the basis of
      Langmuir and Freundlich isotherms. Adsorption of enrofloxacin on natural zeolite
      was found to be highly pH dependent, exhibiting increases correspondent to
      decreases in pH. The positive value of enthalpy change showed the endothermic
      nature of adsorption processes. The presence of ammonium ion enhanced the
      adsorption of enrofloxacin. In the second part of the study, infrared (IR)
      spectroscopy, and scanning electron microscopy (SEM) were used for the
      determination of the modifications on the zeolite surfaces resulting from
      adsorption and ozone treatment. It was found that ozone at sufficient
      concentrations over specified time periods was able to decompose the enrofloxacin
      adsorbed on zeolite.

PMID- 15967282
TI  - On the occasional biodegradation of pharmaceuticals in the activated sludge
      process: the example of the antibiotic sulfamethoxazole.
AB  - Sulfamethoxazole, a common antibiotic, was found to be biodegradable under
      aerobic conditions. The fate of sulfamethoxazole in the activated sludge process
      was studied using a Sequencing Batch Reactor (SBR). Aerobic biomass was
      acclimated to sulfamethoxazole and a series of kinetic experiments were conducted
      to investigate the impact of other carbon and nitrogen sources on the degradation
      of the antibiotic. It was found that sulfamethoxazole serves both as carbon and
      nitrogen source for the enriched consortium. It was degraded whenever there was a
      depletion of carbon or nitrogen or both in the feeding medium, while in the
      presence of acetate and ammonium nitrogen (alternative carbon and nitrogen
      sources, respectively), sulfamethoxazole remained intact.

PMID- 15967283
TI  - The role of terminal-link stimuli in concurrent-chain schedules: revisited using
      a behavioral-history procedure.
AB  - A behavioral-history procedure was used to study the function of terminal-link
      stimuli as conditioned reinforcers in multiple concurrent-chain schedules of
      reinforcement. First, three pigeons were exposed to multiple concurrent-chain
      schedules in which the two multiple-schedule components were correlated with a
      blue and a white stimulus, respectively. In each component the initial links were
      equal independent variable-interval (VI) 15 s schedules. A fixed-interval (FI) 10
      s schedule operated on the red key in one terminal link while extinction operated
      on the green key in the alternative terminal link. When large preferences for the
      red stimulus had been established, two tests were conducted. In the terminal-link
      test, under new initial-link stimuli--purple and brown--an FI 10 s schedule
      operated for both the red and green terminal-link stimuli. In the subsequent
      initial-link test, the blue and white initial-link stimuli were reintroduced,
      and, as in the terminal-link test, FI 10s operated for both the red and the green
      terminal-link stimuli. In the terminal-link test, the three pigeons showed no
      preference for the terminal links with the red stimulus, but showed clear and
      consistent preferences for the red stimulus when blue and white stimuli were
      reintroduced as initial-link stimuli in the initial-link test. This suggests that
      there are multiple sources of control over initial-link response allocation in
      concurrent-chains, including control by both terminal- and initial-link stimuli.

PMID- 15967284
TI  - Visual discrimination learning in zebrafish (Danio rerio).
AB  - Three experiments demonstrated visual discrimination learning in zebrafish (Danio
      rerio). In each experiment, zebrafish were given a choice between two visually
      distinct arms of a T-maze. Choice of one stimulus was always followed by a food
      reward, but choice of the other stimulus was not rewarded. Different colored
      sleeves fitted around the arms of the T-maze were used in Experiments 1 (green
      and purple) and 2 (red and blue). The stimuli used in Experiment 3 were white
      sleeves lined with horizontal or vertical black stripes. In all three
      experiments, zebrafish acquired a significant preference for the stimulus that
      led to a food reward. Experiments 1 and 2 also showed that zebrafish could learn
      a reversal of the discrimination. Finally, the effect of discontinuing food
      rewards was examined after reversal training in Experiment 2 and after initial
      discrimination training in Experiments 1 and 3. Non-reinforcement led to a
      decrease in correct responding in Experiments 2 and 3 independent of stimulus
      identity, but to an asymmetrical pattern of responding in Experiment 1. The
      median latency to make a choice response decreased over the course of acquisition
      in all three experiments; during extinction, median response times did not change
      at all in Experiment 1 and increased only very slightly in Experiment 2, but
      showed a substantial increase in Experiment 3. The implications of these results
      for the zebrafish as a model system for genetic studies of learning and memory
      are discussed.

PMID- 15967285
TI  - A competitive low-affinity binding model for determining the mutual and specific
      sites of two ligands on protein.
AB  - A competitive low-affinity binding model was proposed for determining the number
      of mutual (overlapped) and specific binding sites of two ligands (A, B) on a
      protein (P). To use the model, one needs to carry out a titration experiment by
      adding either ligand A or B into a three-component system (A-B-P), and to monitor
      the spectroscopic parameter changes. Fitting the titration curve to the proposed
      model, one can get the mutual and specific binding sites of the two ligands on
      the protein. The model was examined by using human serum albumin (HSA) as a
      receptor and tolmetin (TOL) and salicylic acid (SAL) as ligands. Proton
      longitudinal relaxation rates (R1) were measured on a 500-MHz NMR spectrometer
      during the titration and used to derive the mutual binding sites. It was found
      that among the binding sites of 32+/-4 for SAL and 28+/-2 for TOL on HSA, there
      were 17+/-5 mutual sites for the two ligands. This result indicates that,
      although HSA has large binding capacities for most ligands, there are still a
      reasonable amount of the low-affinity binding sites that are structure selective.

PMID- 15967286
TI  - Analysis and comparison of Radix Glycyrrhizae (licorice) from Europe and China by
      capillary-zone electrophoresis (CZE).
AB  - A simple capillary-zone electrophoresis (CZE) method for the analysis of plant
      specimens, Glycyrrhiza glabra L., G. uralensisFisch. and G. inflata Bat.
      (Leguminosae) as well as commercial licorices from Europe and China was
      developed. Contents of glycyrrhizin (GL), glycyrrhetic acid (GA), glabridin
      (GLAB), liquiritin (LQ) and licochalcone A (LC(A)) in ethanolic extracts were
      investigated. Optimum separation was achieved with sodium tetraborate buffer (pH
      9.22; 70 mM); voltage, 25 kV. Recovery rate for GL was found to be 101.90+/
      2.54%. Adequate correlation was observed between GL contents measured by CZE and
      HPLC (r=0.977). Advantages over conventional HPLC analysis of Glycyrrhiza species
      are short analysis time (<15 min), simple running buffer preparation and the none
      use of organic solvents. Using the present CZE method, it was demonstrated that
      (1) G. glabra was distinguished from G. uralensis especially by phenolic
      compounds GLAB (G. glabra: 0.19+/-0.11%; n=53) and LQ (G. uralensis, 1.34+/
      0.34%, n=10); (2) on average, GL contents were higher in Chinese commercial
      licorices; (3) relatively high LC(A) contents were especially detected in a
      Chinese commercial licorice (origin estimated as G. inflata); (4) Glycyrrhiza
      species were also distinguished by applying PCA on the basis of CZE peak area
      data of GL, GLAB, GA, LQ and LC(A); and (5) liquiritin apioside was found in all
      samples.

PMID- 15967287
TI  - Enantioselective capillary electrophoretic separation of tryptophane- and
      tyrosine-methylesters in a dual system with a tetra-oxadiaza-crown-ether
      derivative and a cyclodextrin.
AB  - Different dual selector systems containing a cyclodextrin derivative (methyl-beta
      cyclodextrin and dimethyl-beta-cyclodextrin) and a new diaza-crown-ether
      derivative (N-[2-(1,4,10,13-tetraoxa-7,16-diazacyclooctadecan-7
      yl)propanoyl]glycine) were studied in the enantioselective separation of
      tryptophan-methylester and tyrosine-methylester enantiomers. This paper deals
      with the systematic study of the effects of changing the composition of the
      background electrolyte on the resolution of the d- and l- forms using an
      experimental design approach. It was found that the dual systems allowed a better
      chiral separation of the amino acid derivatives. The experimental design approach
      also allowed improving the separation compared to the starting conditions (center
      point of the design), which were adopted from a previous study.

PMID- 15967288
TI  - Use of the zirconia-based stationary phase for separation of ibuprofen and its
      impurities.
AB  - A new reversed-phase liquid chromatographic method using zirconia-based
      stationary phase was developed for determination of ibuprofen, its related
      compounds and its main degradation products. The chromatographic separation was
      successfully achieved on the Discovery Zr-PS column (150 mm x 4.6 mm i.d., 5
      microm), using a mobile phase methanol-phosphate buffer (pH 4.5; 0.05 M)
      tetrahydrofurane (21:74:5, v/v/v) and the flow rate 0.5 ml min(-1). The UV
      detection was performed in dual wavelength mode (219 and 258 nm) to detect all
      compounds of interest. The column temperature was set on 60 degrees C to shorten
      the analysis time and improve the peak symmetry. The method is simple, rapid and
      cuts down the amount of hazardous waste produced in the analysis. The assay is
      completed within 22 minutes.

PMID- 15967289
TI  - Determination of trimebutine in pharmaceuticals by differential pulse voltammetry
      at a glassy carbon electrode.
AB  - The differential pulse voltammetric (DPV) determination of trimebutine (TMB) was
      achieved at a glassy carbon electrode in acetonitrile/0.1 M LiClO4. Trimebutine
      gave two irreversible, diffusion controlled peaks at 740 and 1318 mV versus
      Ag/AgCl reference electrode, respectively. The second oxidation peak was used to
      determine trimebutine concentrations in the range 1-50 microg ml(-1) with a
      detection limit (3sigmam) of 0.3 microg ml(-1). Precision of the method (RSD,
      n=6) within- and between-days obtained from six determinations at 5 microg ml(-1)
      was found to be 0.7 and 1.1%, respectively. The method was successfully applied
      to the quantitation of TMB in granule dosage form (Debridat) and recoveries
      between 98.4 and 101% were obtained. Excipients did not interfere with the assay
      and the results agreed well with those determined by previously established HPLC
      method.

PMID- 15967290
TI  - Chemically modified carbon paste electrode for the potentiometric flow injection
      analysis of piribedil in pharmaceutical preparation and urine.
AB  - A new carbon paste electrode selective for piribedil (PD) was prepared and fully
      characterized in terms of composition, usable pH range, response time and thermal
      stability. The electrode active recognition is by liquid ion-exchange mechanism
      via the use of piribedil phosphomolybdate as ion-exchanger dissolved in tricresyl
      phosphate as a more suitable solvent mediator for the paste. The modified
      electrode showed a Nernstian slope of 58.4+/-0.6 mV over the concentration range
      of 7.5 x 10(-7) to 1 x 10(-3)M with an average recovery of 98.3-101.0% and R.S.D.
      of 0.45-1.31%. The electrode exhibits good selectivity for PD with respect to a
      large number of inorganic cations, organic cations, sugars and amino acids. The
      developed electrode was successfully used for the potentiometric determination of
      PD in its aqueous solutions, pharmaceutical preparation, and urine in batch and
      flow injection analysis (FIA).

PMID- 15967291
TI  - Selection of excipients for extended release formulations of glipizide through
      drug-excipient compatibility testing.
AB  - For the development of extended release formulations of glipizide, techniques of
      thermal and isothermal stress testing (IST) were used to assess the compatibility
      of glipizide with selected excipients. Initially, differential scanning
      calorimeter (DSC) was used to evaluate the compatibility. IR spectrum of drug
      excipient mixture was also compared with that of pure drug and excipient.
      Compatibility of excipients defined in the prototype formula was tested using
      IST. Based on the DSC results alone, magnesium stearate, meglumine, TRIS buffer,
      and lactose, were found to exhibit interaction with glipizide. Stressed binary
      mixtures (stored at 50 degrees C for 3 weeks) of glipizide and meglumine showed
      yellow coloration indicating potential incompatibility. Based on the results of
      DSC, IR, and/or HPLC, excipients defined in the prototype formula were found to
      be compatible with glipizide. The optimized formulation developed using the
      compatible excipients were found to be stable after 3 months of accelerated
      stability studies (40 degrees C and 75% RH). Overall, compatibility of excipients
      with glipizide was successfully evaluated using the combination of thermal and
      IST methods and the formulations developed using the compatible excipients was
      found to be stable.

PMID- 15967292
TI  - Electrochemical genosensing of the interaction between the potential
      chemotherapeutic agent, cis-bis(3-aminoflavone)dichloroplatinum(II) and DNA in
      comparison with cis-DDP.
AB  - The interaction of cis-diamminedichloroplatinum(II) (cis-DDP) and the potential
      novel chemotherapeutic agent, cis-bis(3-aminoflavone)dichloroplatinum(II) (cis
      BAFDP) was studied electrochemically with calf thymus double-stranded DNA (dsDNA)
      by using differential pulse voltammetry (DPV) with disposable pencil graphite
      electrode (PGE) at the surface. These studies were prompted by beneficial
      biological properties of cis-BAFDP in comparison with cis-DDP, which were proven
      in vitro both in human normal and cancer cells and in vivo. The changes in the
      experimental parameters such as the concentration of cis-DDP and cis-BAFDP were
      studied by using DPV; in addition, the reproducibility of this genosensor and the
      detection limit for each compound were determined. After the interaction of cis
      DDP with dsDNA, the DPV signal of guanine and adenine was found to be decreasing.
      In comparison with cis-DDP, a dramatic decrease at adenine signal was also
      obtained after the interaction of cis-BAFDP and dsDNA. Similar results were also
      found in solution phase after the latter compound interacts with poly[A]. The
      features of the proposed electrochemical method for the detection of cis-BAFDP
      with DNA in comparison with cis-DDP are discussed and compared with those methods
      previously reported for the other type of DNA-targeted agents in the literature.

PMID- 15967293
TI  - Precision from drug stability studies. Investigation of reliable repeatability
      and intermediate precision of HPLC assay procedures.
AB  - A multi-company investigation is presented to obtain and compare precision
      results for LC assay procedures. Forty-four drug substances and drug products of
      various types subjected to 156 stability studies, with 2915 assay values in
      total, were included. This provides an excellent source of real long-term
      precision estimates, as the same analytical procedure was applied during the
      whole stability study, extending from 12 to 60 months. Intermediate precision was
      calculated either using the residual standard deviation of the regression line or
      applying an analysis of variances, depending on whether there was a significant
      degradation of the analyte or not. The results show impressively the large
      intervals where the individually calculated parameters scatter. Distribution
      ranges and averages for repeatability, intermediate precision, and the ratio
      between the two precision levels are mainly dependent on the type of drug
      product. Repeatabilities were found up to 0.8% for solutions, 1.6% for drug
      substances, 1.9% for tablets, 2.3% for creams, and 3.4% for a bath. For
      intermediate precision, which includes additional variability factors due to the
      reference standard, operator, equipment, reagents, etc., a similar dependency was
      obtained with a slightly changed order: up to 1.1% for drug substances, 2.2% for
      solutions, 2.3% for tablets, 3.1% for creams, and 3.2% for a bath. The ratio
      between the precision levels is up to 2.5 and similar for all investigated drug
      product types, apart from solutions with up to 5.3. These differences for the
      types of drug product may be explained by the influence of the sample and/or the
      sample preparation: the more complex, the higher the variability contribution.
      For the investigated examples, the impact of the analyte and of the concentration
      (dosage) seems to be of less importance. Therefore, a classification of drug
      product types for orientation on acceptable precision (ranges) for LC assay seems
      to be possible.

PMID- 15967294
TI  - Hypothesis of potential active components in Angelica sinensis by using
      biomembrane extraction and high performance liquid chromatography.
AB  - The screening and analysis of bioactive components in traditional Chinese
      medicines (TCMs) is very important not only for the quality control of crude
      drugs but also for elucidating the therapeutic principle. In this study, a method
      for screening potential active components from TCMs was developed by using
      biomembrane extraction and high performance liquid chromatography. Based on the
      methodology, aqueous extract of Angelica sinensis (WEAS) was used, and four
      compounds were detected by HPLC in the desorption eluate of red cell membrane
      extraction for WEAS. The compounds were identified as ferulic acid, ligustilide,
      senkyunolide H and senkyunolide I based on their UV, MS and NMR spectra.
      Actually, ferulic acid and ligustilide are considered as major active components
      in Angelica sinensis. Therefore, this method may be applied to predict the
      potential bioactivities of multiple compounds in TCMs simultaneously.

PMID- 15967295
TI  - Analysis of the acid-base reaction between solid indomethacin and sodium
      bicarbonate using infrared spectroscopy, X-ray powder diffraction, and solid
      state nuclear magnetic resonance spectroscopy.
AB  - Indomethacin was used as a model compound to investigate acid-base reactions of
      solid materials, a common type of drug-excipient interaction. In a typical
      experiment, 500 mg of pure alpha-form indomethacin were mixed with 500 mg of
      sodium bicarbonate. The mixture was kept at 40 degrees C and at several relative
      humidities. The reaction was monitored by IR spectroscopy, X-ray powder
      diffraction, and solid-state NMR. At 40 degrees C and 80% RH, the reaction is
      nearly complete after 300 h. As observed by IR spectroscopy, the characteristic
      peaks of alpha-indomethacin disappear during the course of the reaction with the
      appearance of the characteristic peaks of the salt product, sodium indomethacin
      trihydrate. Solid-state NMR spectra and X-ray powder diffraction patterns of the
      reaction mixtures confirm the transformation of the mixtures to sodium
      indomethacin trihydrate; the reduced peak intensities in the diffraction patterns
      of the product relative to the initial mixtures indicate the formation of a
      microcrystalline product. A change in the reaction rate of sodium bicarbonate
      with alpha-indomethacin is observed when the mixtures are stored at different
      relative humidities. At 40 degrees C and 66% RH, the reaction of sodium
      bicarbonate with alpha-indomethacin is about 86% complete after 500 h. No
      detectable reaction was observed for sodium bicarbonate with the alpha form of
      indomethacin at 40 degrees C and 11% RH after 15 months. The combination of these
      solid-state characterization techniques is demonstrated to be essential to detect
      and monitor acid-base reactions in solid materials, which are impossible to
      monitor using solution-chemistry methods. The reaction kinetics at 66% RH fits
      the Jander equation very well, which is consistent with a diffusion-controlled
      mechanism.

PMID- 15967296
TI  - LC-UV method development and validation for the investigational anticancer agent
      imexon and identification of its degradation products.
AB  - Imexon (4-imino-1,3-diazabicyclo[3,1,0]-hexan-2-one) is a member of the class of
      2-cyanoaziridine derivatives, which have been of interest as immunomodulators and
      anticancer agents since the late 1970s. The pharmaceutical development of imexon
      necessitated the availability of an assay for the quantification and purity
      determination of imexon active pharmaceutical ingredient (API) and the drug in
      its pharmaceutical dosage form. A liquid chromatographic (LC) method with
      ultraviolet (UV) detection was developed, using a reverse phase column with
      phosphate buffer (pH 6; 50 mM) as mobile phase and UV detection at 230 nm.
      Although retention capacity for imexon was small (capacity factor of 0.5), the
      method was found to be linear over the concentration range of interest of 1.0-25
      microg/mL, precise, accurate, and stability-indicating. Moreover, the use of LC
      mass spectrometry (MS) and on-line photodiode array (PDA) detection enabled us to
      propose structures for four degradation products. Two of these products were also
      found as impurities in the API. The degradation products, including chloro- and
      hydroxy-derivatised products were shown to arise from nucleophilic reactions with
      the activated aziridine moiety of imexon. The developed LC-UV method was found
      suitable for the pharmaceutical quality control of imexon API and the drug in its
      pharmaceutical dosage form.

PMID- 15967297
TI  - Determination of potato carboxypeptidase inhibitor in African Green Monkey plasma
      using 96-well SPE and LC-MS/MS.
AB  - Potato carboxypeptidase inhibitor (CPI), a peptide with multiple isoforms
      (MW>4000 Da) was determined from African Green Monkey plasma using a PE Sciex API
      3000 LC-MS/MS in the positive ionization mode with the turbo ionspray interface
      (450 degrees C). Samples were prepared using an Oasis MCX 96-well solid phase
      extraction plate and chromatographed on an Allure C18 HPLC Column (50 mm x 1.0
      mm, 5 microm) using gradient elution. Upon analysis of the extracts using LC
      MS/MS, the concentration of CPI was calculated using a single MS/MS transition
      (m/z 830.5-->221.0) that was reflective of the mass concentration (microg/mL) of
      main the CPI isoforms present in plasma from monkeys after they were given an
      intravenous dose of CPI. The assay was linear for CPI over concentrations of 0.05
      10 microg/mL when extracting 200-microL aliquots of African Green Monkey plasma.
      The assay was applied to the determination of CPI in African Green Monkey plasma
      samples in two separate analytical runs (correlation of standard curves,
      r1=0.9991 and r2=0.9953). Quality control (QC) samples were run at 0.05, 0.1,
      0.2, 0.5, 1.0, 2.0 and 5.0 microg/mL for each assay. Average ranges (n=12) for
      accuracy and precision for all concentrations of QCs during the two runs were
      92.0-102.0% of expected potency and 10.4-21.8% (coefficient of variations),
      respectively.

PMID- 15967298
TI  - A one-step, competitive electrochemiluminescence-based immunoassay method for the
      quantification of a fully human anti-TNFalpha antibody in human serum.
AB  - A quantitative, one-step, competitive electrochemiluminescence (ECL)-based
      immunoassay for the determination of a fully human, anti-TNFalpha monoclonal
      antibody in human serum has been developed. A biotinylated, mouse anti-variable
      region-specific antibody and a ruthenium-labeled anti-TNFalpha antibody were the
      only specific reagents needed to develop the assay. A single incubation step of 2
      h followed by ECL detection was used. The assay was capable of measuring the
      analyte in neat serum over approximately a 1600-fold range with higher
      concentrations measured following a single dilution. Assay accuracy, precision,
      and reproducibility were suitable to support pharmacokinetic studies of the
      analyte. This competitive assay format offers an alternative approach to the
      development of immunoassays for the measurement of macromolecules in complex
      matrices to support preclinical and clinical studies.

PMID- 15967299
TI  - Migration of diethylhexyl phthalate from PVC bags into intravenous cyclosporine
      solutions.
AB  - The migration of diethylhexyl phthalate (DEHP) from PVC bags into LVPS (0.9%
      NaCl) and LVPS with cyclosporine at concentrations of 2.5 and 0.5mg/ml was
      studied. PVC bags were placed in contact with these solutions and stored at 25+/
      1 degrees C. They were taken for analysis each 30 min during 6 h and after this
      period at each 1 h until 12 h of contact. Water was used as reference, and
      exposed and analyzed under the same conditions. After contact, the solutions were
      submitted to extraction with hexane and analyzed by GC-FID. The results showed
      that DEHP did not migrate into water and LVPS during all the time. Also, no
      measurable amount of DEHP was detected during the first 3 h of contact between
      the PVC bag and the diluted cyclosporine solution. However, the amount of
      released DEHP reached a detectable level after 4 h of contact, increased until 6
      h, stabilized, and increased again after 9-10 h. The 12 h of contact showed the
      highest DEHP levels for both cyclosporine concentrations. The DEHP migrated was
      0.02-0.08% of that present in the bag.

PMID- 15967300
TI  - Determination of ibuprofen in dog plasma by liquid chromatography and application
      in pharmacokinetic studies of an ibuprofen prodrug in dogs.
AB  - A liquid chromatography (LC) method for the determination of ibuprofen in dog
      plasma is described. Chromatographic separation was performed on a Diamonsil C18
      column with a C18 guard column using a binary mixture of acetonitrile and 0.02
      mol/l phosphate buffer (pH 6.5) (35:65, v/v) delivered at a flow rate of 1.2
      ml/min. The linear range for ibuprofen was from 1.0 to 40.0 microg/ml with a
      limit of quantitation of 1.0 microg/ml. Within-run accuracy and precision ranged
      from -0.1% to 4.0% and from 1.1% to 5.5% and between-run accuracy and precision
      ranged from -1.1% to 4.7% and from 1.3% to 7.0%, respectively. The mean
      extraction recoveries of ibuprofen determined over the concentrations of 1.0,
      10.0, and 40.0 microg/ml were (100.5+/-1.8)%, (99.8+/-1.0)%, and (99.2+/-2.3)%.
      The developed LC method greatly simplified the sample preparation and adopted
      mild conditions to prevent the possible hydrolysis of the prodrug and was
      successfully applied to the pharmacokinetic studies of an ibuprofen prodrug in
      dogs.

PMID- 15967301
TI  - Simultaneous quantification of atomoxetine as well as its primary oxidative and O
      glucuronide metabolites in human plasma and urine using liquid chromatography
      tandem mass spectrometry (LC/MS/MS).
AB  - A sensitive and selective liquid chromatography tandem mass spectrometry
      (LC/MS/MS) method for the determination of atomoxetine and its metabolites (4
      hydroxyatomoxetine, N-des-methylatomoxetine, and 4-hydroxyatomoxetine-O
      glucuronide) has been developed for human plasma and urine. Using stable-labeled
      internal standards, the method proved to be accurate and precise for the analytes
      in all species, resulting in inter-batch accuracy (percent relative error, %RE)
      within 100+/-13% and inter-batch precision (relative standard deviation, %RSD)
      within 11%. Stability was demonstrated for the analytes in neat solutions and the
      reconstitution solvent, as well as plasma and urine (with or without the
      deconjugation reagent). The method was simple, robust (utilized for the analysis
      of several hundred clinical study samples), and amenable to high sample
      throughput.

PMID- 15967302
TI  - Hydrophilic interaction liquid chromatography-APCI-mass spectrometry
      determination of 5-fluorouracil in plasma and tissues.
AB  - A simple and fast analytical method using hydrophilic interaction liquid
      chromatography (HILIC) coupled with mass spectrometry was developed to analyse 5
      fluorouracil (5-FU) in plasma and tissues. The HILIC system overcomes problems
      reported in obtaining satisfactory retention of 5-FU with other types of HPLC
      systems. After addition of internal standard (IS) (5-Chlorouracil (5-CU)), plasma
      proteins were precipitated with acetonitrile, and tissue samples homogenised with
      a micro-dismembrator. The analysis was performed using a polymer-based column
      (Ashaipak NH2) and the compounds were eluted under gradient conditions at 1
      ml/min using a mobile phase containing a mixture of ammonium formate and
      acetonitrile. MS detection used a API 4000 mass spectrometry with heated
      nebulizer source and multiple reaction monitoring operated in the negative ion
      mode. The mass transitions of 5-FU and its internal standard were 129 m/z-->42m/z
      and 145 m/z-->42 m/z, respectively. The lower limits of quantitation in plasma
      and tissues were about 5 ng/ml and 10 ng/g, respectively, using 25 microl of
      plasma and 50mg of tissue. Good linearity, accuracy and precision were obtained
      in all matrices tested. The suitability and robustness of the method for in vivo
      samples were confirmed by analysis of mouse plasma, muscle and tumour from
      animals dosed with 5-FU.

PMID- 15967303
TI  - Development of an HPLC method for determination of diphenidol in plasma and its
      application in an oral multi-dose bioequivalence study in a healthy female
      Mexican population.
AB  - Diphenidol was determined by an HPLC method developed in our laboratory. It was
      validated and proved to be linear in the 40-400 ng/ml range. Accuracy for quality
      control samples for intra and inter day assays ranged from 96.1-98.9% and 98.8
      101.4%, respectively. This method was applied to a multi-dose bioequivalence
      study. No serious side effects were observed in the multi-dose design.
      Pharmacokinetic parameters (mean+/-standard error [S.E.]) of Cavg (ng/ml) and
      AUCtau (ngh/ml) for reference and test products were 139.54+/-12.66 versus
      148.60+/-16.51 and 551.07+/-53.53 versus 588.78+/-69.02, respectively. Log
      transformed values were compared by analysis of variance (ANOVA) followed by the
      classical 90% confidence interval (CI 90%) test and Schuirmann's test. Confidence
      limits ranged from 91.48-116.18% for Cmax and from 91.24-117.65% for AUCtau.
      These results suggest that the analytical method was linear, precise, and
      accurate for our purpose, and that both assayed formulations were bioequivalent.

PMID- 15967304
TI  - Development and validation of a HPLC-UV method for the determination in
      didanosine tablets.
AB  - A simple, rapid, sensitive and specific reversed-phase high performance liquid
      chromatographic method involving ultraviolet detection (HPLC-UV) was developed
      for analysis of didanosine in drug substance and formulated products, tablets.
      Chromatography was carried out on a pre-packed, Lichrospher 100 Rp-8 (5.0 microm,
      250 mm x 4.0 mm) column using 0.01 M sodium acetate solution:methanol (85:15,
      v/v) adjusted to pH 6.5 with acetic acid as mobile phase at a flow rate of 1.5
      ml/min and a 248 nm detection. Hypoxantine was confirmed as the main degradation
      product. The assay was linear over the concentration range of 50-150 microg/ml (R
      approximately 0.999). The method was validated for accuracy and precision.

PMID- 15967305
TI  - HPLC method development for testosterone propionate and cipionate in oil-based
      injectables.
AB  - Two isocratic liquid chromatographic methods for the determination of
      testosterone propionate (TP) and cipionate (TC) in oil-based injectables using
      methyltestosterone and bolasterone as internal standards, respectively, have been
      developed and validated. Mobile phases 57% water:acetonitrile 43% (v:v) and 54%
      water:acetonitrile 46% (v:v) were used for TP and TC, respectively. For both
      methods, a bonded-silica Luna CN (250 mm x 4.6 mm i.d., 5 microm) (25 degrees C)
      column, a flow-rate 1 ml min(-1) and UV absorbance detection at 245 nm were used
      and two separations up to base line were achieved. Prior to HPLC analysis, sample
      preparation was required, including extraction of TP and TC from oil-based
      injectables using the surfactant sodium dodecyl sulphate.

PMID- 15967306
TI  - A novel gradient HPLC method for simultaneous determination of ranitidine,
      methylparaben and propylparaben in oral liquid pharmaceutical formulation.
AB  - A selective and accurate high-performance liquid chromatographic method has been
      developed and validated for the simultaneous determination of ranitidine,
      methylparaben (MP) and propylparaben (PP) in oral liquids. Samples were purified
      by solid-phase extraction (SPE) using a copolymeric [poly(divinylbenzene-co-N
      vinylpyrrolidone)] sorbent. The chromatographic separation was achieved by HPLC
      using a mixture of ammonium acetate solution (0.5 M), acetonitrile and methanol
      as the mobile phase with gradient elution, a Nucleosil C18 column and UV
      detection at 254 nm. The method was validated with respect to linearity,
      precision, accuracy, selectivity, and robustness. All the parameters examined met
      the current recommendations for bioanalytical method validation. The method was
      found to be applicable to routine analysis (assays and stability tests) of active
      compound (ranitidine) and preservatives (MP and PP).

PMID- 15967307
TI  - Electrochemical study of imipenem's primary metabolite at the mercury electrode.
      Voltammetric determination in urine.
AB  - Imipenem shows a fast chemical conversion to the more stable imin form (identical
      to that from biochemical dehydropeptidase degradation) in aqueous solutions that
      shows a wave at lower cathodic potential than the imipenem one. The aim of this
      work is the study of the electrochemical behaviour of the primary metabolite of
      imipenem (M1) and the proposal of electrochemical methods for the determination
      of M1 in human urine samples. Electrochemical studies were realized in phosphate
      buffer solutions over pH range 2.0-8.0 using differential pulse polarography, dc
      tast polarography, cyclic voltammetry and linear sweep voltammetry (staircase).
      In acidic media, a non-reversible diffusion-controlled reduction involving two
      electrons and two protons occurs and the mechanism for the reduction was
      suggested. A differential pulse polarographic method for the determination of M1
      in the concentration range 10(-6) to 10(-4)M with a detection limit of 4.5 x 10(
      7)M was proposed. Also, a method based on controlled adsorptive pre-concentration
      of M1 on the hanging mercury drop electrode (HMDE) followed by linear sweep
      voltammetry allows its determination in the concentration range 2 x 10(-9) to 4 x
      10(-8)M with a detection limit of 1.05 x 10(-9)M. The proposed methods have been
      used for the direct determination of M1 in spiked human urine and real human
      derived urine with good results and should be appropriate for monitoring
      purposes.

PMID- 15967308
TI  - A stability-indicating HPLC assay for metronidazole benzoate.
AB  - A simple and rapid stability-indicating HPLC assay procedure has been developed
      and validated for metronidazole benzoate. The HPLC conditions were as follows,
      column: Waters Symmetry C8, 5 microm packing, 4.6 mm x 250 mm; detection: UV at
      271 nm; injection volume: 20 microl; mobile phase: acetonitrile-0.1% glacial
      acetic acid in monobasic potassium phosphate (0.01 M) (40:60, v/v); isocratic
      elution under ambient temperature at 2.0 ml min(-1). The procedure separated
      metronidazole benzoate and its potential degradation products, metronidazole and
      benzoic acid, in an overall analysis time of about 6 min with metronidazole
      benzoate eluting at about 5 min. The injection repeatability was 0.03%, and the
      intraday and interday repeatability were 0.4 and 0.7%, respectively. The
      procedure provided a linear response over the concentration range 0.2-800 microg
      ml(-1) (r=1.0000) with the limits of detection and quantitation 0.03 and 0.2
      microg ml(-1), respectively. The solubilities of metronidazole benzoate in water,
      0.01 M hydrochloric acid and 0.05 M phosphate buffer, pH 6.8, determined each in
      triplicate using the procedure, were 0.2 mg ml(-1) (R.S.D. 7%), 0.4 mg ml(-1)
      (R.S.D. 2%) and 0.2 mg ml(-1) (R.S.D. 8%), respectively. The results show no
      detectable hydrolysis of metronidazole benzoate in 0.01 M hydrochloric acid at 37
      degrees C or in the mobile phase at ambient temperature in 10 h.

PMID- 15967309
TI  - Stable isotopic composition of the active pharmaceutical ingredient (API)
      naproxen.
AB  - A survey of the multi-stable isotopic composition of an active pharmaceutical
      ingredient (API), naproxen, was performed to assess the potential of Isotope
      Ratio Mass Spectrometry (IRMS) to distinguish the provenance of APIs. Twenty-six
      lots of naproxen from six manufacturers representing four countries (Italy,
      India, Ireland, and the USA) were analyzed for three isotope ratios (13C/12C,
      18O/16O, and D/H). The samples were analyzed by either Elemental Analyzer/Isotope
      Ratio Mass Spectrometry (EA/IRMS: carbon (delta13C)) or by Thermal Conversion
      EA/IRMS (TCEA/IRMS: hydrogen (deltaD) and oxygen (delta18O)). Bivariate and
      trivariate isotope ratio graphs for naproxen show marked clustering of the data
      for five out of the six naproxen manufacturers, suggesting that IRMS may be a
      plausible means to screen for manufacturer of given APIs.

PMID- 15967310
TI  - A fluorescence optosensor for analyzing naphazoline in pharmaceutical
      preparations. Comparison with other sensors.
AB  - We have developed an optical sensor for determining and quantifying naphazoline
      (NPZ) based on its inherent fluorescence property. We have placed a non-ionic
      exchanger solid support (Amberlite XAD-7) in a flow cell in the light path of the
      excitation beam and the fluorescence signal for NPZ is continuously monitored at
      lambda(exc/nm)=294/306 nm. The response time for this sensor is acceptably fast,
      80s, obtaining a detection limit of 2.6 ng mL(-1) with standard deviations of
      2.0% at 125 ng mL(-1). This device has been satisfactorily applied to two
      commercial formulations and its selectivity has been demonstrated with an
      interference study. The advantages have been compared with the only published
      sensor for determining NPZ in pharmaceutical preparations and with other
      analytical methods in the literature.

PMID- 15967311
TI  - Identification of degradation products of diclofenac by electrospray ion trap
      mass spectrometry.
AB  - The degradation products of diclofenac in aqueous dosage form in accelerated
      storage conditions were characterized by electrospray ionization-ion trap mass
      spectrometry (ESI-MS). Liquid chromatography (LC)-MS analyses revealed the
      presence of three degradation products. ESI-MS(n) spectra were used to study
      diclofenac fragmentation in detail and to characterize the structures of
      degradation products. A previously described degradation product, formed by a
      cyclization reaction of diclofenac producing the indolinone derivative, was
      found. As any hydroxylated product was found, no oxidation seems to occur in the
      dosage form used. On the contrary, two degradates have been detected and
      identified, leading to a primary alcohol structure or an aldehyde function in
      place of the acetate group of diclofenac.

PMID- 15967312
TI  - Posterior arthrodesis of the spine by percutaneous CT-guided application of
      screws: preliminary report.
AB  - We report our preliminary results obtained in five patients following a
      percutaneous posterior arthrodesis of the spine, executed under fluoroscopic
      control and CT guidance. To benefit from a mechanical fixation after an anterior
      osteosynthesis without the inconveniences of the classic posterior surgical
      intervention, we have adopted a procedure performed under local anesthesia and
      based on the intraarticular application of screws. The procedure is CT-guided,
      resulting in a perfect localization of the area involved, it is safe, and it is
      performed in a short time limiting, therefore, possible neurological, vascular,
      or visceral complications.

PMID- 15967313
TI  - Classification of breast ultrasound images using fractal feature.
AB  - Fractal analyses have been applied successfully for the image compression,
      texture analysis, and texture image segmentation. The fractal dimension could be
      used to quantify the texture information. In this study, the differences of gray
      value of neighboring pixels are used to estimate the fractal dimension of an
      ultrasound image of breast lesion by using the fractal Brownian motion.
      Furthermore, a computer-aided diagnosis (CAD) system based on the fractal
      analysis is proposed to classify the breast lesions into two classes: benign and
      malignant. To improve the classification performances, the ultrasound images are
      preprocessed by using morphology operations and histogram equalization. Finally,
      the k-means classification method is used to classify benign tumors from
      malignant ones. The US breast image databases include only histologically
      confirmed cases: 110 malignant and 140 benign tumors, which were recorded. All
      the digital images were obtained prior to biopsy using by an ATL HDI 3000 system.
      The receiver operator characteristic (ROC) area index AZ is 0.9218, which
      represents the diagnostic performance.

PMID- 15967314
TI  - Optimization of tube potential-filter combinations for film-screen mammography: a
      contrast detail phantom study.
AB  - This study evaluated how tube potential-filter combinations [with a molybdenum
      (Mo) anode and either an Mo or a rhodium (Rh) filter] influence image quality and
      radiation dose to breasts of different thicknesses in film-screen mammography
      using a new mammography phantom (CDMAM Phantom Type 3.4). A 28-kVp/Mo tube
      potential-filter combination is recommended for a breast (phantom) thickness of
      40 mm or less, 28 kVp/Rh for a breast (phantom) thickness of 60 mm or less, and
      30 kVp/Rh for a breast (phantom) thickness greater than 60 mm.

PMID- 15967315
TI  - MR features of gastrointestinal stromal tumors.
AB  - We report on two patients presenting with gastrointestinal stromal tumors (GIST).
      The important tumor size and the marked tissular hypersignal seen on T2-weighted
      magnetic resonance images (MRI) should be considered as magnetic resonance (MR)
      features strongly indicating diagnosis of GIST.

PMID- 15967316
TI  - The value of contrast-enhanced helical CT scan with rectal contrast enema in the
      diagnosis of acute appendicitis.
AB  - BACKGROUND: The aim of this retrospective study is to assess the accuracy of
      single slice helical CT scan with intravenous, and rectal contrast (CTRC) in the
      diagnosis of acute appendicitis (AA) in patients with suspected AA, with
      particular analysis of the diagnostic signs. PARTICIPANTS AND METHODS: Abdomino
      pelvic helical CTRC was performed on 75 consecutive patients with suspicion of
      AA. Radiologic diagnosis was compared with surgical/pathologic results and
      clinical follow-up. In addition, the CTRC examinations were retrospectively
      reviewed independently by two experienced radiologists using predefined
      diagnostic criteria. The sensitivity, specificity, and frequency of each
      diagnostic sign were calculated. The interobserver agreement and the statistical
      significance of the frequency for each diagnostic criterion were assessed using
      the Kappa and Fisher tests, respectively. RESULTS: The accuracy of helical CTRC
      in the diagnosis of AA was 94.7%, sensitivity 100%, specificity 90%, PPV 89.7%,
      and the NPV 100%. Wall enhancement and nonopacification of the appendix recorded
      the highest sensitivity and specificity (97% and 100%, 94% and 95%,
      respectively). Appendiceal thickness greater than 6 mm was present in 100% of
      true-positive cases. However, 26.5% of true-negative cases had also an
      appendiceal diameter exceeding 6 mm, a value used as a cut-off for normal
      appendiceal diameter. The highest interobserver agreement was recorded for
      appendiceal wall enhancement and for nonopacification of the appendix (K=0.97 and
      0.88, respectively). CONCLUSIONS: CTRC is an accurate and relatively fast
      technique for investigation of patients with suspected AA. A negative CTRC can
      exclude completely the diagnosis of AA. Nonopacification of the appendix and
      appendiceal wall enhancement are highly sensitive, specific, and reproducible,
      signs representing major criteria for the diagnosis of AA.

PMID- 15967317
TI  - Radiology-Pathology Conference: carcinosarcoma of the colon.
AB  - Carcinosarcomas are very uncommon tumors, which are comprised of both malignant
      epithelial and mesenchymal elements. They occur most commonly in the head and
      neck, respiratory tract, and female reproductive organs. In the gastrointestinal
      tract, they are most often found in the oropharynx, esophagus, and, to a lesser
      extent, in the stomach. Carcinosarcomas rarely originate from the colon, but when
      they do, they are extremely aggressive malignancies. We report the radiologic and
      pathologic findings of a patient with a carcinosarcoma believed to have arisen
      from the colon and which involved the adjacent mesentery and omentum.

PMID- 15967318
TI  - Multiphasic CT and MRI appearances of extramedullary multiple myeloma involving
      the stomach, pancreas, and bladder.
AB  - Multiple myeloma is a hematological malignancy characterized by the uncontrolled
      proliferation of clonal plasma cells. Skeletal involvement is one of its
      hallmarks, while extraosseous involvement is comparatively uncommon. There have
      been no previous reports of the imaging findings of multiple myeloma involving
      the stomach, pancreas, and bladder in the same patient. The stomach and
      pancreatic lesions were demonstrated as hypervascular nodules on computed
      tomography (CT), more conspicuous on arterial phase images. Early phase post
      contrast imaging might improve the detection of extraosseous myeloma.

PMID- 15967319
TI  - Indeterminate small, low-attenuating hepatocellular nodules on helical CT in
      patients with chronic liver disease: 2-year follow-up.
AB  - To evaluate the clinical significance of indeterminate, small, low-attenuating
      nodular lesions on helical dynamic computed tomography (CT) in chronic liver
      diseases, CT images were reviewed retrospectively in 281 patients. Indeterminate,
      low-attenuating nodular lesions less than 20 mm in diameter were followed for 24
      to 35 months. Of 127 nodules in 73 patients, 21 nodules turned out to be
      hepatocellular carcinomas (16%), 25 nodules (20%) became larger, while the
      remaining 81 nodules (64%) remained unchanged or disappeared. Some low
      attenuating nodules larger than 10 mm in diameter may develop into hepatocellular
      carcinoma.

PMID- 15967320
TI  - Acromioclavicular joint osteoarthritis: comparison of findings derived from MR
      imaging and conventional radiography.
AB  - The purpose of this study was to determine the correlation between routine
      radiography and magnetic resonance (MR) imaging in the analysis of the
      acromioclavicular (AC) joint osteoarthritis (OA). MR imaging studies of the
      shoulder in 50 patients performed over a 1-year period at a single institution
      with corresponding conventional radiographic examinations performed within 1
      month of the MR imaging study were restrospectively evaluated by the consensus of
      two musculoskeletal radiologists with special attention to the AC joint. As
      conclusion, information provided by conventional radiography in the analysis of
      AC joint OA does not correlate with that provided by MR imaging. AC joint OA is
      more frequently detected with MR imaging than with radiography. MR imaging
      provides better assessment of the full extent of AC joint OA and its effect on
      the underlying RC.

PMID- 15967321
TI  - MR imaging of the elbow: a spectrum of common pathologic conditions.
AB  - The following pictorial essay is a review of common elbow pathology as seen on
      elbow MR imaging. These include pathologic conditions that involve tendons,
      ligaments, osseous structures, bursa and other miscellaneous and incidentally
      detected lesions.

PMID- 15967322
TI  - Evidence of cerebral reorganization following perinatal stroke demonstrated with
      fMRI and DTI tractography.
AB  - A 44-year-old man with a left perinatal stroke and recurrent refractory epilepsy
      underwent functional MRI (fMRI) for motor and language mapping to determine if
      further epilepsy surgery could be performed without loss of language. Language
      was activated excessively in the right hemisphere, with only small areas of left
      hemisphere activation. This suggests bilateral language dominance acquired
      secondary to the perinatal stroke with the right hemisphere activation resulting
      from neonatal neuronal reorganization. Functional data were overlaid onto 3D
      diffusion tensor tractography, providing a unique image of the right hemisphere
      language recruitment.

PMID- 15967323
TI  - Transdural spinal cord herniation: pre- and postoperative MRI findings.
AB  - Idiopathic transdural spinal cord herniation (ICSH), a rare condition which may
      cause progressive myelopathy, can be diagnosed preoperatively by MRI. Surgical
      treatment usually results in the resolution of symptoms and, thus, familiarity
      with the imaging findings in this condition impacts patient management. We
      present the case of a 36-year-old woman in whom the initial MRI findings were
      thought to be consistent with only an arachnoid cyst compressing the spinal cord.
      After surgery, her symptoms remained unchanged, and a repeat MRI study was
      interpreted as being compatible with a transdural spinal cord herniation.
      Repeated surgery with reduction of the herniation resulted in significant
      clinical improvement.

PMID- 15967324
TI  - Massive recurrent synovial sarcoma of the hip: radiologic-histologic correlation
      in a case of failed magnet therapy.
AB  - We report the unusual case of a recurrent, massive synovial sarcoma of the hip,
      following magnet therapy failure.

PMID- 15967325
TI  - Eleventh international conference on screening for lung cancer.

PMID- 15967326
TI  - The variable risk of colorectal cancer in patients with inflammatory bowel
      disease.

PMID- 15967327
TI  - Training in modern medicine: Should objectives be modified?

PMID- 15967328
TI  - Cardiovascular protection in patients with type 2 diabetes mellitus:
      Considerations about the tightness of blood pressure control and the choice of
      treatment.
AB  - Diabetes mellitus is rapidly evolving as the epidemic of the 21st century. The
      presently estimated number of 190 million is predicted to grow to over 300
      million by the year 2025. Cardiovascular (CVD) morbidity and mortality is two to
      five times higher in diabetics, while the microvascular complications
      considerably compromise the quality of life. The main risk factors for CVD, as
      well as for microangiopathy, are hypertension, dyslipidemia, insulin resistance,
      hyperglycemia, endothelial dysfunction, and an inflammatory vascular reaction.
      This review will focus on hypertension, which develops in most patients within
      the first 10-15 years of their diabetes. The discussion will encompass the
      criteria for treatment, the target values of blood pressure, and the choice of
      antihypertensive drugs as primary agents and in various combinations. The special
      role of angiotensin-receptor blockers will be highlighted, with an emphasis on
      cardioprotection, risk reduction of stroke, and attenuation of the course of
      nephropathy.

PMID- 15967329
TI  - The diagnostic spectrum of unintentional weight loss.
AB  - Significant and documented involuntary weight loss in adults frequently poses a
      diagnostic challenge to the clinician. We summarize published series on the
      etiologies and the outcomes of involuntary weight loss and use these data to
      formulate a proposal for a diagnostic work-up. Simple, non-invasive screening
      tests, embarking from thorough history-taking and clinical examination, are
      advocated first. Additional testing should be directed towards areas of concern
      raised by this initial evaluation. If a well-thought-out baseline examination is
      reassuring and fails to provide further clues, a strategy of watchful waiting
      with close clinical follow-up is preferred to a blind pursuit of additional, more
      invasive, or expensive investigations.

PMID- 15967330
TI  - A training course for the Israeli phase I written board examination in internal
      medicine increases the success rate of foreign graduate physicians.
AB  - BACKGROUND: Foreign graduate residents in internal medicine perform poorly on the
      Israeli phase I written board examination as compared to local graduates from
      Israeli medical schools. The aim of this study was to determine the effect of a
      preparatory course, aimed at foreign graduates, on their success rate in the
      Israeli phase I written board examination in internal medicine. METHODS: The
      preparatory course consisted of seven 4-h weekly meetings that took place 3
      months before the board examination. Participants were divided into two classes,
      each containing approximately 35 residents. Each meeting was dedicated to two
      fields of internal medicine and consisted of a multiple-choice examination,
      followed by a guided discussion with a senior physician. A pre-test was given at
      the end of the course and its results were compared to those of the official
      examination. Residents who took the official examination but who did not
      participate in the course served as controls. RESULTS: The combined 2-year (1999
      2000) success rate on the official phase I board examination of foreign graduates
      who took the course was significantly higher than that of controls: 41.7% vs.
      30.4%, respectively (p<0.019). The results of the course pre-test were highly
      predictive of the success on the board examination (r=0.481, p<0.01). The course
      did not significantly improve the success rate of the Israeli graduates.
      CONCLUSION: A short, focused, preparatory course significantly increases the
      success rate of foreign graduate residents on the Israeli phase I written board
      examination in internal medicine. Performance in the course is highly predictive
      of the success rate on the official board examination.

PMID- 15967331
TI  - Inflammatory bowel disease-related dysplasia and cancer: A referral center study
      in northwestern Greece.
AB  - BACKGROUND: An increased risk of colorectal cancer in ulcerative colitis (UC) and
      Crohn's disease (CD) has been reported. No data on inflammatory bowel disease
      (IBD)-related dysplasia and cancer is available in Greece, where the disease
      profile seems to be milder than that of northern Europe. METHODS: A study was
      conducted of 215 IBD patients (182 with UC, 33 with CD) from a referral center.
      Patients were followed up for 3-18 years. The prevalence of cancer and dysplasia
      among the IBD patients who were diagnosed in northwestern Greece was analyzed and
      registered. Statistical analysis was performed assuming that this IBD cohort had
      the same risk of developing malignancies as the general population in Greece.
      RESULTS: Six of the 215 patients in this IBD cohort had cancer, and 20 of 126
      patients for whom bowel biopsies were available had dysplasia. Three of these
      cases were high-grade dysplasia. There was no significant difference in the
      numbers of calculated and expected cases of IBD-related cancer at any sites
      except for the skin [2.7 vs. 2.0]. CONCLUSIONS: This IBD cohort did not appear to
      have an increased risk of cancer during the time period studied. It would be
      interesting to re-assess the risk after the second and third decades of follow
      up.

PMID- 15967332
TI  - Inflammatory bowel disease associated with Yersinia enterocolitica O:3 infection.
AB  - BACKGROUND: Certain microorganisms may be associated with the development of
      inflammatory bowel disease (IBD). These pathogens may possess such properties as
      immunological capability or tissue invasiveness. An association between Yersinia
      enterocolitica infection and ulcerative colitis (UC) was suggested 30 years ago,
      and a connection with Crohn's disease (CD) may also exist. The aim of this study
      was to further elucidate the association between Y. enterocolitica O:3 infection
      and IBD. METHODS: During the period 1990-1997, antibody response against Y.
      enterocolitica was estimated in 1588 patients by tube agglutination. Forty-one
      patients with Y. enterocolitica infection (titer = 320) constituted the study
      group; 1041 patients without antibody response constituted the control group. The
      study was completed in 2003, after 6-13 years. RESULTS: At diagnosis of Y.
      enterocolitica infection, UC of acute onset was demonstrated in three males;
      another suffered from CD. At follow-up, two additional patients had developed UC
      and two CD. In the control group, 32 patients were diagnosed as having UC and 10
      CD. This difference in IBD prevalence is significant (8/41>42/1041, p=0.00035),
      as were the differences in prevalence of UC and CD separately (p=0.006; viz.
      p<0.015). CONCLUSION: The present study supports the concept of the Y.
      enterocolitica infection as a trigger of chronic IBD.

PMID- 15967333
TI  - Silent versus cranial giant cell arteritis. Initial presentation and outcome of
      50 biopsy-proven cases.
AB  - BACKGROUND: The objective of the present study was to compare the silent form of
      giant cell arteritis (GCA) to the classic cephalic form of the disease. METHODS:
      We conducted a retrospective study based on a chart review of 50 consecutive,
      biopsy-proven GCA, recorded at a department of internal medicine. We sought to
      distinguish a silent form, defined by a prolonged inflammatory syndrome or fever
      of unknown origin with the absence of cephalic signs, polymyalgia rheumatica, or
      large artery involvement, from an overt "classic" cranial temporal arteritis.
      RESULTS: The prevalence of the silent form of GCA was 46% in our study. Abnormal
      temporal arteries were more frequent in the cephalic group. The silent GCA group
      had higher C-reactive protein levels (p<0.05), a higher platelet count (p<0.05),
      and lower serum albumin (p<0.05). There was no significant difference in temporal
      artery specimens in the two groups. Clinical relapses tended to be more frequent,
      and patients free of corticosteroids tended to be less frequent, in the cephalic
      group, though the difference was not statistically significant. CONCLUSIONS: The
      silent and cephalic forms of GCA could have distinct clinical and biological
      patterns and different outcomes. The limitation of our study was its
      retrospective design. Further studies are required to determine if this
      distinction is useful in treating GCA patients.

PMID- 15967334
TI  - High prevalence of subclinical peripheral artery disease in Greek hospitalized
      patients.
AB  - BACKGROUND: Peripheral artery disease (PAD) represents a common manifestation of
      systemic atherosclerosis that is associated with an increased risk of
      cardiovascular death and ischemic events but one that may be underdiagnosed in
      clinical practice. The purpose of this study was to identify PAD using the ankle
      brachial index (ABI) in hospitalized patients from a Department of Internal
      Medicine and to further investigate the association of this index with
      traditional cardiovascular risk factors. METHODS: We measured ABI in 990
      consecutive patients (400 men and 590 women) aged 50 years or older (71.2+/-9.1)
      without a history or symptoms suggestive of PAD. ABI values below 0.90 were
      considered abnormal. RESULTS: PAD was detected in 356 patients (36%), and men had
      a higher prevalence than women (p<0.001). Hypertension (p<0.001), smoking
      (p<0.001), diabetes (p<0.05), male sex (p<0.001), and dyslipidemia (p<0.05) were
      statistically more frequent in patients with PAD, whereas obesity had no
      significant relation to PAD in our series. In a stepwise, logistic regression
      analysis, hypertension, male sex, diabetes mellitus, smoking, and dyslipidemia
      were found to be independent risk factors with odds ratios (95% confidence
      intervals) of 2.46 (1.85-3.27), 2.25 (1.66-3.05), 1.80 (1.32-2.47), 1.78 (1.31
      2.42), and 1.64 (1.22-2.19), respectively. CONCLUSIONS: A simple ABI measurement
      revealed a large number of patients with unrecognized PAD. It is, therefore,
      recommended that ABI measurement should be included in the evaluation of
      cardiovascular risk in hospitalized patients aged 50 years or older.

PMID- 15967335
TI  - Statin escape phenomenon: Does it really exist?
AB  - BACKGROUND: The normalization of blood lipid profile has become an accepted
      method of primary and secondary prevention of vascular disease, with statins
      being the most popular group of medicines prescribed to lower cholesterol and LDL
      cholesterol levels. The failure of statins, administered in an appropriate dose,
      to maintain the optimal level of LDL cholesterol is a rare phenomenon, and is
      still not well understood in patients compliant for both medication and diet. The
      entity of "statin escape phenomenon", proposed to explain the failure of statins
      in some of these patients, has not been studied or characterized extensively, and
      reports of its prevalence are scarce. METHODS: Patients with hyperlipidemia type
      2a or 2b who had been treated with statins for at least 1 year and who were
      followed up in the lipid clinic on a regular basis every 3-4 months were included
      in this study. The charts of patients whose LDL cholesterol levels were elevated
      by 15% or more while receiving the same treatment were analyzed, and patients
      with putative statin escape phenomenon were included in the study and further
      characterized. RESULTS: Forty-five of 358 statin-treated patients demonstrated a
      15% increase in LDL cholesterol levels, leading to suspicion of statin escape
      phenomenon. However, a strict exclusion analysis left only two patients without
      evident potential triggers for the observed elevation in LDL cholesterol.
      CONCLUSIONS: Whether a statin escape phenomenon really exists is still not
      certain, but if it does exist, it is probably an uncommon event with a low
      prevalence.

PMID- 15967336
TI  - The prediction of in-hospital mortality by amino terminal pro-brain natriuretic
      peptide (NT-proBNP) levels and other independent variables in acutely ill
      patients with suspected heart disease.
AB  - BACKGROUND: Amino terminal pro-brain natriuretic peptide (NT-proBNP) measurement
      can detect and assess heart failure. However, compared with traditional clinical
      parameters, its value in predicting the in-hospital mortality of patients with
      suspected heart disease has not been reported. METHODS: We examined the ability
      of 11 continuous and 21 categorical variables, including NT-proBNP levels
      measured at the time of admission, to predict in-hospital mortality. The setting
      was a small Irish rural hospital where 342 consecutive patients with suspected
      heart disease were admitted as acute medical emergencies. RESULTS: The 31
      patients who died while in hospital had significantly higher NT-proBNP levels on
      admission than patients discharged alive (11,548+/-13,531 vs. 3805+/-6914 pg/mL,
      p<0.0001). Patients who died in-hospital were older, had significantly higher
      white cell counts, blood urea and modified early warning (MEW) scores, and lower
      temperatures, blood pressures and oxygen saturation. Four variables were found to
      be independent predictors of in-hospital mortality: a systolic blood pressure
      equal to or below 100 mm Hg, a urea level above 13 mmol/L, a white cell count
      greater than 13*10(9)/L and a NT-proBNP level greater than or equal to 11,500
      pg/mL. The presence of three of these variables was associated with an in
      hospital mortality rate of 54%. CONCLUSIONS: Four variables (i.e. hypotension,
      elevated urea, leukocytosis and elevated NT-proBNP levels) are comparable
      independent predictors of in-hospital mortality.

PMID- 15967337
TI  - Porta-cath complicated by IVC thrombosis.
AB  - We present an observational case report describing the clinical history and
      pathologic findings of a patient with an in situ porta-cath for acute
      intermittent porphyria who developed an inferior vena caval (IVC) thrombosis. CT
      contrast studies showed a possibly infected IVC thrombosis below the level of the
      renal vessels, extending into the iliacs, formed around the porta-cath. Acute
      intermittent porphyria was precipitated by complications arising from the
      thrombus. Consequently, the patient was unable to receive prophylactic
      medication.

PMID- 15967338
TI  - Severely elevated serum triglycerides in a case of heterozygous familial
      hypercholesterolemia with the 317 cysteine to serine mutation in the LDL receptor
      gene.
AB  - We present a case of a 43-year-old Japanese man with heterozygous familial
      hypercholesterolemia (FH) with severely elevated serum triglycerides (TG). He
      drank large quantities of alcohol but had no endocrinological disorder or
      diabetes mellitus. He had a recurrent, acute pancreatitis. His fasting serum
      total cholesterol (TC), TG, and HDL-C levels and an apolipoprotein E genotype of
      E3/E3 suggested a diagnosis of type V hyperlipidemia. Yet, the patient had
      bilateral Achilles tendinous xanthomata, which prompted us to conduct a gene
      analysis for the LDL receptor, and this revealed the heterozygous form of the 317
      cysteine to serine mutation, demonstrating that this was a case of FH. We
      recommend that physicians consider the existence of FH, even in hyperlipidemic
      subjects with lipid profiles far from those typical of FH, whenever a patient has
      tendinous xanthomata.

PMID- 15967339
TI  - An unusual cause of recurrent syncope: Mediastinal lymphoma diagnosed with
      transesophageal echocardiography.
AB  - Non-Hodgkin's lymphoma (NHL) rarely presents initially with cardiac symptoms. In
      this case, its first symptom was a recurrent syncope. The diagnosis of
      mediastinal tumor was made with transesophageal echocardiography. Considerable
      compression of the left atrium and superior vena cava without intracardiac growth
      was a cause of the syncope. Tumor biopsy revealed a diffuse, high-grade, large B
      cell NHL. The patient died after four cycles of chemotherapy. To our knowledge,
      no previous report has demonstrated a syncope as an initial presentation of
      mediastinal lymphoma not invading the heart.

PMID- 15967340
TI  - Urticarial vasculitis revealing relapsing polychondritis.
AB  - We report a case of hypocomplementemic urticarial vasculitis heralding a
      relapsing polychondritis in a 63-year-old woman. The patient, who had suffered in
      the past from polymyalgia rheumatica, suddenly experienced a generalized
      urticarial eruption with a dramatic decrease in C4 complement fraction and the
      presence of anti-C1q antibodies. Two months later, an ear chondritis occurred and
      the patient rapidly responded to steroids and dapsone. To our knowledge, this
      association has never been reported.

PMID- 15967341
TI  - Acute hepatitis related to prednisolone.
AB  - A 46-year-old woman, known to have multiple sclerosis (MS), presented with
      repeated episodes of elevated liver enzymes due to high-dose methylprednisolone
      therapy.

PMID- 15967342
TI  - Bladder and bowel dysfunction in chronic inflammatory demyelinating
      polyradiculoneuropathy.
AB  - We present a patient with chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) who developed severe bladder and bowel dysfunction
      (BBD) as evidenced by constipation, voiding difficulty, and urinary urgency.
      These symptoms appeared 10 years after onset of CIDP. Cystometry showed
      disturbance of bladder sensation and detrusor areflexia. Magnetic resonance
      imaging (MRI) showed greatly enlarged nerve roots filling the lumbosacral spinal
      canal; this appeared to be the likely cause of BBD. A 3-day course of intravenous
      methylprednisolone (1 g/day), followed by 30 mg/day of oral prednisolone,
      ameliorated the sensory disturbance and muscle weakness, but not BBD.

PMID- 15967343
TI  - Political issues in internal medicine in Europe. A position paper.
AB  - What will be the future of internal medicine in Europe? Because of rapidly
      growing concerns regarding the position of internal medicine in many European
      countries, the European Federation of Internal Medicine (EFIM) has established a
      working group to analyze the situation. Being well aware of the variation in
      working practices in the different countries, the members of the group used an
      "all-European" approach to answer the following questions: Internal medicine is
      the modern, clinical, and scientific medical discipline that is responsible for
      the care of adult patients with one or more complex, acute, or chronic illnesses.
      Internal medicine is the cornerstone of an integrated health care delivery
      service that is needed today. Decision-makers in politics and hospitals,
      insurers, journalists, and the general public need a better understanding of what
      internal medicine can offer to the health care system and to the individual
      patient.

PMID- 15967344
TI  - Usefulness of oral vitamin B12 therapy in vitamin B12 deficiency related to food
      cobalamin malabsorption: Short and long-term outcome.

PMID- 15967345
TI  - A retroperitoneal abscess causing hydronephrosis: An unusual sequela of ERCP.

PMID- 15967346
TI  - Obstetric medicine: A key role for the internist.

PMID- 15967347
TI  - Structured thin films as functional components within biosensors.
AB  - This review provides an introduction to the field of thin films formed by
      Langmuir-Blodgett or self-assembly techniques and discusses applications in the
      field of biosensors. The review commences with an overview of thin films and
      methods of construction. Methods covered will include Langmuir-Blodgett film
      formation, formation of self-assembled monolayers such as gold-thiol monolayers
      and the formation of multilayers by the self-assembly of polyelectrolytes. The
      structure and forces governing the formation of the materials will also be
      discussed. The next section focussed on methods for interrogating these films to
      determine their selectivity and activity. Interrogation methods to be covered
      will include electrochemical measurements, optical measurements, quartz crystal
      microbalance, surface plasmon resonance and other techniques. The final section
      is dedicated to the functionality of these films, incorporation of biomolecules
      within these films and their effect on film structure. Species for incorporation
      will include antibodies, enzymes, proteins and DNA. Discussions on the location,
      availability, activity and stability of the included species are included. The
      review finishes with a short consideration of future research possibilities and
      applications of these films.

PMID- 15967348
TI  - Formation and characterization of glutamate dehydrogenase monolayers on silicon
      supports.
AB  - In this paper we have tested two different procedures (the "three-step" and the
      "four-step" procedures) for the covalent immobilization of glutamate
      dehydrogenase (GDH) onto silicon supports. Atomic force microscopy (AFM), Fourier
      transform infrared spectroscopy (FT-IR), fluorescence spectroscopy and an
      enzymatic assay were used to probe the structure and activity of the immobilized
      enzyme. Our results demonstrate that coupling through the "three-step" procedure
      does not significantly affect either the fold pattern or the activity of the
      enzyme, suggesting that this method could be ideally suited to the development of
      high quality monolayers for use in enzyme-based planar biosensors.

PMID- 15967349
TI  - Continuous measurements of a binding reaction using a capacitive biosensor.
AB  - A capacitive biosensor with polyclonal antibodies raised against human serum
      albumin (HSA) immobilized on a gold transducer has been developed for continuous
      measurement of HSA in the muM-range. A mathematical model has been refined to
      describe integral HSA-binding curves assuming that (i) binding is essentially
      irreversible under the conditions used, (ii) the signal is scaled as the number
      of non-occupied binding sites and (iii) the rate of disappearance of available
      binding sites is scaled as the number of available binding sites and analyte
      concentration in solution. Deconvolution of the curves using the mathematical
      model indicates clearly that it is possible to retrieve concentration profiles
      (isocratic, linearly or exponentially increasing gradients) of the analyte in the
      continuous sample flow from the normalized integral binding (NIB) curves. The
      data presented constitutes the theoretical background and the first step towards
      the development of an analytical system allowing on-line detection of the
      concentration profile of the analyte from NIB-curves. Since the system can be
      used for extended time periods between regeneration steps, a low frequency of
      regeneration steps can be expected.

PMID- 15967350
TI  - On the response of a label-free interferon-gamma immunosensor utilizing
      electrochemical impedance spectroscopy.
AB  - The research on our flow-injection, label-free, non-faradaic impedimetric
      immunosensor for interferon-gamma (IFN-gamma) has been extended. The sensor is
      prepared by immobilization of anti-IFN-gamma antibodies on a self-assembled
      monolayer (SAM) of acetylcysteine, deposited on polycrystalline gold. A multi
      frequency impedance method is described, which allows time-resolved measurement
      of Nyquist plots. To these plots, an equivalent circuit was fitted, which is
      discussed in terms of a two-layer structure (inner and outer layer) of the
      interfacial region. Because binding of IFN-gamma mainly causes a decrease of Q (a
      constant-phase element), this element is considered as the outer layer. Several
      aspects of the impedimetric sensor response are studied, including the dependence
      on detection frequency, target concentration and applied dc potential. For
      quantitative detection of IFN-gamma, an optimum of the signal-to-noise (S/N)
      ratio of the out-of-phase impedance component (Z'') was found at about 100 Hz. At
      a dc-potential of +0.2 V versus a saturated calomel reference electrode, the
      sensor response is higher than at 0.0 V. Logarithmic dose-response curves of IFN
      gamma in the concentration range of 10(-18) to 10(-9) M were obtained using two
      procedures: by successive injections over a single electrode, and by using
      freshly prepared electrodes for each measurement. Using the latter method, the
      repeatability is impaired. The need for in situ complementary techniques for a
      correct interpretation of the studied parameters is discussed.

PMID- 15967351
TI  - Study of real-time lectin-carbohydrate interactions on the surface of a quartz
      crystal microbalance.
AB  - A quartz crystal microbalance (QCM) biosensor system for lectin-carbohydrate
      interactions has been developed. Yeast mannan was immobilised on polystyrene
      coated quartz crystals, and interactions tested with the lectin concanavalin A
      (Con A). The biosensor could be easily operated, where mannan immobilisation and
      all binding analyses were performed in real-time using a flow-through system. The
      apparent binding constant for yeast mannan to Con A was estimated to be 0.4
      microM, well in accordance to reported literature values. In addition, the
      effective concentration values (EC50-values) for a series of mannose/mannoside
      ligands, acting as competitors to the mannan/Con A interaction, were determined
      to range from 0.18 to 5.3 mM, in good correlation with a related enzyme-labelled
      lectin assay (ELLA) protocol.

PMID- 15967352
TI  - Development of photocatalytic biosensor for the evaluation of biochemical oxygen
      demand.
AB  - The photocatalytic biosensor of flow system using semiconductor TiO2 was
      developed to evaluate biochemical oxygen demand (BOD) levels in river water.
      Photocatalysis of sample was carried out in a photoreactor with TiO2 and a 6W
      black-light blue fluorescent tube as light source. Sample from a photoreactor
      outlet was measured by an oxygen electrode with a biofilm. The sensor response of
      photocatalytic biosensor was between 5 and 10 min depending on concentration of
      biochemical in the samples. At BOD of 1 mgl-1, the sensor response increased 1.33
      fold in comparison with that without photocatalysis. The degradation of tannic
      acid and humic acid with photocatalysis were 51.8 and 38.4%, respectively. Gum
      arabic and linear alkylbenzene sulfonate (LAS) were degraded a little, but gave
      the responses of more than double to the sensor. Free radicals yielded by
      photocatalysis in a photoreactor did not affect the sensor response because their
      lifetime is extremely short. Fairly good correlation (r=0.983) between the sensor
      method and the conventional method was obtained for test samples. This biosensor
      using photocatalytic pretreatment improved the sensitivity.

PMID- 15967353
TI  - Determination of hydrogen peroxide using amperometric sensor of polyaniline doped
      with ferrocenesulfonic acid.
AB  - The result of cyclic voltammetry shows that polyaniline doped with
      ferrocenesulfonic acid (PAnFc) can effectively catalyze the oxidation of hydrogen
      peroxide, so PAnFc is used as a sensor to determine the concentration of H2O2.
      Iron in the ferrocenesulfonic acid exists in two oxidation states: Fe2+ and Fe3+.
      They can reversibly oxidize and reduce between the Fe2+ and Fe3+ oxidation
      states, which play an important role in the catalytic oxidation of H2O2. The
      response current of the sensor depends on the pH, applied potential and
      temperature at a given concentration of H2O2. At optimum conditions, the sensor
      has a fast response to H2O2, good operational stability, a good linear response
      to H2O2 in the range from 4 to 64 microM, and a small temperature dependence of
      the response current.

PMID- 15967354
TI  - Quartz crystal microbalance-with dissipation monitoring (QCM-D) for real time
      measurements of blood coagulation density and immune complement activation on
      artificial surfaces.
AB  - A recently developed variant of quartz crystal microbalance (QCM) called QCM-with
      dissipation monitoring (QCM-D) allows simultaneous and simple measurements of
      changes in adsorbed mass as well as the viscoelastic property (D-factor) of
      deposited protein layers on the sensor surface. We have taken the QCM-D
      technology a step further and demonstrated its advantages in the study of protein
      assembly as a consequence of surface induced immune complement activation, or
      contact activated blood coagulation. In the present study we have continued our
      QCM-D investigations of surface assembly of fibrin clot formation and complement
      activation and incubated differently modified quartz sensor surfaces in blood
      plasma and sera. Polymer surfaces used were spin-coated polyethylene,
      poly(ethylene terephtalate), poly(methylmetacrylate) and poly(dimethylsiloxane).
      Also used were sputtered titanium and heparin grafted surfaces. In this
      investigation we found that we could describe the surface induced coagulation
      with four independent parameters: (1) Time of onset of coagulation, (2) fibrin
      deposition rate, (3) total frequency shift at stable plateau, and (4) fibrin clot
      density. The most important finding was that the blood plasma clot density can be
      assessed with the use of D determinations and that the clot density varied
      significantly with the chemical composition of the surface. However, the D-factor
      did not give any new analytical information about the possible complement
      activation mechanisms. Nevertheless, the QCM-D was found to be a reliable tool
      for the analysis of surface induced complement activation. We also compared the
      QCM-D technique with traditional enzyme immuno assay (EIA) measurements of
      soluble products from the surface activation of the complement and coagulation
      systems. We found that the results from EIA and QCM-D measurements corresponded
      well for the complement activation but not for the coagulation, probably due to
      the biological complexity of the coagulation system.

PMID- 15967355
TI  - Carbon fibre-based microbiosensors for in vivo measurements of acetylcholine and
      choline.
AB  - This report describes technical improvements to the manufacture of a carbon fibre
      electrode for the stable and sensitive detection of H2O2 (detection limit at 0.5
      microM). This electrode was also modified through the co-immobilisation of
      acetylcholinesterase (AChE) and/or choline oxidase (ChOx) in a bovine serum
      albumin (BSA) membrane for the development of a sensor for in vivo measurements
      of acetylcholine and choline. Amperometric measurements were performed using a
      conventional three-electrode system forming part of a flow-injection set-up at an
      applied potential of 800-1100 mV relative to an Ag/AgCl reference electrode. The
      optimised biosensor obtained was reproducible and stable, and exhibited a
      detection limit of 1 microM for both acetylcholine and choline. However, due to
      the high operating potential used, the biosensor was prone to substantial
      interference from other electroactive compounds, such as ascorbic acid.
      Therefore, in a further step, a mediated electron transfer approach was used that
      incorporated horseradish peroxidase into an osmium-based redox hydrogel layered
      onto the active surface of the electrode. Afterwards, a Nafion layer and a
      coating containing AChE and/or ChOx co-immobilised in a BSA membrane were
      successively deposited. This procedure further increased the selectivity of the
      biosensor, when operated in the same flow-injection system but at an applied
      potential of -50 mV relative to an Ag/AgCl reference electrode. The sensor
      exhibited good selectivity and a high sensitivity over a concentration range (0.3
      100 microM) suitable for the measurement of choline and acetylcholine in vivo.

PMID- 15967356
TI  - Synthesis and spectral properties of DNA capped CdS nanoparticles in aqueous and
      non-aqueous media.
AB  - Synthesis of novel cadmium sulphide nanoparticles has been carried out in aqueous
      and non-aqueous media. DNA has been added during the synthesis of the
      nanoparticles, which results into cadmium-rich nanoparticles forming a stable
      complex with DNA. These particles exhibit strong fluorescence, spectral nature of
      which depends upon the medium in which the particles are synthesized. When
      interacted with proteins, fluorescence peak intensity of CdS nanoparticles
      increases considerably. It is possible that such CdS nanoparticles would be
      useful as a protein sensor.

PMID- 15967357
TI  - Study on orientation of immunoglobulin G on protein G layer.
AB  - A comparative study of immunoglobulin G (IgG) immobilization was performed, both
      on a thiolated protein G layer, where this immobilization was due to affinity
      binding with an Fc fragment of IgG, and on 11-mercaptoundecanoic acid (11-MUA),
      where the immobilization was due to chemical bonding. The change of IgG layer
      formation on the two base layers as a function of the IgG concentration was
      investigated by surface plasmon resonance (SPR), atomic force microscopy (AFM) in
      a non-contact mode, and spectroscopic ellipsometry (SE). It was observed that the
      IgG layer was immobilized more evenly on the thiolated protein G layer than on
      the 11-MUA layer, based on the SPR measurements. The surface topology analysis by
      AFM indicated that the IgG layer was immobilized on the protein G layer according
      to the envelope profile of the base layer. Based on the SE analysis, it was
      determined that the IgG layer thickness on the thiolated protein G layer
      increased with increasing IgG concentration. Based on the above analyses, the
      scheme for orientation of IgG immobilized on the thiolated protein G layer was
      proposed.

PMID- 15967358
TI  - Frog melanophores cultured on fluorescent microbeads: biomimic-based biosensing.
AB  - Melanophores are pigmented cells in lower vertebrates capable of quick color
      changes and thereby suitable as whole cell biosensors. In the frog dermis skin
      layer, the large and dark pigmented melanophore surrounds a core of other
      pigmented cells. Upon hormonal stimulation the black-brown pigment organelles
      will redistribute within the melanophore, and thereby cover or uncover the core,
      making complex color changes possible in the dermis. Previously, melanophores
      have only been cultured on flat surfaces. Here we mimic the three dimensional
      biological geometry in the frog dermis by culturing melanophores on fluorescent
      plastic microbeads. To demonstrate biosensing we use the hormones melatonin and
      alpha-melanocyte stimulating hormone (alpha-MSH) as lightening or darkening
      stimuli, respectively. Cellular responses were successfully demonstrated on
      single cell level by fluorescence microscopy, and in cell suspension by a
      fluorescence microplate reader and a previously demonstrated computer screen
      photo-assisted technique. The demonstrated principle is the first step towards
      "single well/multiple read-out" biosensor arrays based on suspensions of
      different selective-responding melanophores, each cultured on microbeads with
      distinctive spectral characteristics. By applying small amount of a clinical
      sample, or a candidate substance in early drug screening, to a single well
      containing combinations of melanophores on beads, multiple parameter read-outs
      will be possible.

PMID- 15967359
TI  - QCM-FIA with PGMA coating for dynamic interaction study of heparin and
      antithrombin III.
AB  - In this work, we describe a method of constructing a film of linear poly(glycidyl
      methacrylate) (PGMA) polymer onto the surface of quartz crystal microbalance
      (QCM) electrode as a coating material that allows easy coupling of heparin
      molecules onto the electrode and facilitates the determination of the interaction
      between heparin and antithrombin III (AT III). The PGMA film was characterized
      with atomic force microscopy (AFM) and infra-red spectroscopy. The coupling of
      heparin was accomplished in one step solution reaction. A home-made quartz
      crystal microbalance-flow injection analysis (QCM-FIA) system with data analysis
      software developed in our laboratory was used to determine the interaction. The
      interactions between immobilized heparin and AT III were studied with various
      concentrations under various conditions. The obtained constants are kass=(1.49+/
      0.12)x10(3)mol-1ls-1, kdiss=(3.94+/-0.63)x10(-2)s-1, KA=(3.82+/-0.33)x10(4)mol
      1l.

PMID- 15967360
TI  - Analysis of calibration methodologies for solvent effects in drug discovery
      studies using evanescent wave biosensors.
AB  - Recent improvements in sensitivity have enabled direct binding studies of small
      molecules with evanescent wave biosensors, which monitor binding by measuring
      refractive index changes close to the sensing surface. The universal solvent for
      small molecules, dimethylsulfoxide has a high refractive index; consequently, on
      ligate addition a large non-specific solvent effect is seen which can mask the
      specific signal. It has been previously noted that different sensor surfaces can
      respond differently to the same buffer change. The difference is proposed to
      arise from differences in buffer space and contraction and swelling of the
      surface hydrogel. Within this paper, a number of calibration approaches are
      investigated and tested using warfarin binding to human serum albumin as a model
      system. A number of recommendations are made for accurate referencing for non
      specific effects. Changes to the ionic strength of the running buffer had little
      effect, whilst changes to the charge density of the carboxylmethyl dextran
      significantly affected how well the control surface reflects the non-specific
      signal. An amended 'calibration method' can be used, however, it is an additional
      complex step that was found to overcorrect in the presence of non-specific
      binding. Matching immobilisation levels between control and active surface
      significantly reduces solvent differences allowing accurate correction providing
      solvent compositional changes are minimised in experimental design. Under these
      circumstances, the traditional method of simple subtraction of the control from
      the active response is the most appropriate method of correction.

PMID- 15967361
TI  - Construction and characterization of different MutS fusion proteins as
      recognition elements of DNA chip for detection of DNA mutations.
AB  - Three MutS fusion systems were designed as the mutation recognition and signal
      elements of DNA chips for detection of DNA mutations. The expression vectors
      containing the encoding sequences of three recombinant proteins, Trx-His6-GFP
      (Ser-Gly)6-MutS (THGLM), Trx-His6-(Ser-Gly)6-Strep tagII-(Ser-Gly)6-MutS (THLSLM)
      and Trx-His6-(Ser-Gly)6-MutS (THLM), were constructed by gene slicing in vitro.
      THGLM, THLSLM and THLM were then expressed in Escherichia coli AD494(DE3),
      respectively. SDS-PAGE analysis revealed that each of the expected proteins was
      approximately 30% of the total bacterial proteins. The recombinant proteins were
      purified to the purity over 90% by immobilized metal (Co2+) chelation affinity
      chromatography. Bioactivity assay indicated that three fusion proteins retained
      the mismatch-binding activity and the functions of other fusion partners. DNA
      chips arrayed both mismatched and unpaired DNA oligonucleotides as well as rpoB
      gene from Mycobacterium tuberculosis were prepared. THGLM, THLSLM and THLM that
      was labeled with Fluorolinktrade mark Cy3 reactive dye, were then used as both
      mutation recognition and labeling elements of DNA chips. The resulting DNA chips
      were used to detect the mismatched and unpaired mutations in the synthesized
      oligonucleotides and single base mutation in rpoB gene of M. tuberculosis that is
      resistant to rifamycin.

PMID- 15967362
TI  - Amperometric detection of the bacterial metabolic regulation with a microbial
      array chip.
AB  - A microbial array chip with collagen gel spots entrapping living bacterial cells
      has been applied to investigate the metabolic regulation in Paracoccus
      denitrificans. Scanning electrochemical microscopy (SECM) was used to monitor the
      ferrocyanide production that reflects the electron flow in the respiratory chain
      located within the internal membrane of P. denitrificans. The ferrocyanide
      production from P. denitrificans largely depends on the types of the carbon
      source (glucose or lactate), suggesting that the electron flow rate in the
      respiratory chain depends on the activity of the metabolic pathway located up
      stream of the respiratory chain. More importantly, it was found that the enzymes
      affecting glucose catabolic reactions were significantly up-regulated in cultures
      with a nutrient agar medium containing D-(+)-glucose as a sole carbon source.
      Enzyme assays using crude extracts of P. denitrificans were carried out to
      identify the enzymes expressed at a higher level in cultures supplemented with D
      (+)-glucose. It was confirmed that the pyruvate kinase and enzymes of the overall
      Entner-Doudoroff pathway were highly induced in cultures containing D-(+)
      glucose.

PMID- 15967363
TI  - Synergistic substrates determination with biosensors.
AB  - High sensitive biosensors for heterocyclic compounds determination were built
      using oxidases-catalyzed hexacyanoferrate(III) reduction in the presence of these
      compounds. As oxidases Aspergillus niger glucose oxidase and recombinant
      Microdochium nivale carbohydrate oxidase were used. The biosensors were build
      using graphite electrodes and entrapped solution of the oxidases. The sensitivity
      of the biosensors achieves 5.2-14.5 microA microM-1 cm-2. The detection limit of
      some heterocyclic compounds was 0.2 microM. The sensitivity of biosensors was 300
      10,000 times larger in comparison to hexacyanoferrate(III). To background the
      scheme of biosensors action kinetics of synergistic substrates oxidation was
      investigated in homogenous solution. The measurements showed that the rate of the
      reduction of low reactive substrate (hexacyanoferrate(III)) increased due to
      synergistic action of high reactive substrates (oxidized heterocyclic compounds).
      The modeling revealed the limiting step of the process. The increase of
      hexacyanoferrate(III) reduction rate is determined by the rate of reduced enzymes
      interaction with oxidized heterocyclic compound. The oxidation of heterocyclic
      compounds (mediators) with hexacyanoferrate(III) does not limit the process. The
      analysis of macrokinetics of biosensors action showed that synergistic effect may
      be realized and high biosensors sensitivity may be achieved if diffusion module
      of the enzyme reaction with the oxidized mediator and of a cross reaction is
      larger than 0.5. The calculated relative sensitivity is about three times higher
      in comparison to experimentally determined that may be caused by the limited
      stability of oxidized heterocyclic compounds and/or some external diffusion
      limitation of substrates.

PMID- 15967364
TI  - Direct electrochemistry of microperoxidase at Pt microelectrodes modified with
      carbon nanotubes.
AB  - Direct electrochemistry of microperoxidase (MP-11) was found at Pt
      microelectrodes modified with multi-wall carbon nanotubes (MWNTs). The MWNTs used
      as the immobilization matrix cooperatively promote the bioactivity of MP-11. When
      MP-11 was immobilized on MWNTs film-modified Pt microelectrodes, a pair of well
      defined redox waves was obtained. The resulted stable microelectrode could be
      used to catalyze the reduction of H2O2 and O2.

PMID- 15967365
TI  - High-density electrode array for imaging in vitro electrophysiological activity.
AB  - The development of a high-density active microelectrode array for in vitro
      electrophysiology is reported. Based on the Active Pixel Sensor (APS) concept,
      the array integrates 4096 gold microelectrodes (electrode separation 20 microm)
      on a surface of 2.5 mmx2.5 mm as well as a high-speed random addressing logic
      allowing the sequential selection of the measuring pixels. Following the
      electrical characterization in a phosphate solution, the functional evaluation
      has been carried out by recording the spontaneous electrical activity of neonatal
      rat cardiomyocytes. Signals with amplitudes from 130 microVp-p to 300 microVp-p
      could be recorded from different pixels. The results demonstrate the suitability
      of the APS concept for developing a new generation of high-resolution
      extracellular recording devices for in vitro electrophysiology.

PMID- 15967366
TI  - Immunosensor for the diagnosis of Chagas' disease.
AB  - Trypanosoma cruzi proteins from epimastigote membranes, herein referred as
      antigens, have been used for the construction of an amperometric immunosensor for
      serological diagnosis of Chagas' disease. The proteins used had a molecular mass
      ranging from 30 to 100 kDa. The gold electrode was treated with cysteamine and
      glutaraldehyde prior to antigen immobilization. Antibodies present in the serum
      of patients with Chagas' disease were captured by the immobilized antigens and
      the affinity interaction was monitored by chronoamperometry at a potential of 
      400 mV (versus Ag pseudo-reference electrode) using peroxidase-labeled IgG
      conjugate and hydrogen peroxide, iodide substrate. The incubation time to allow
      maximum antigen-antibody and antibody-peroxidase-labeled IgG interactions was 20
      min with a reactivity threshold at -0.104 microA.

PMID- 15967367
TI  - Direct electrochemical sensor for fast reagent-free DNA detection.
AB  - A novel reagentless direct electrochemical DNA sensor has been developed using
      ultrathin films of the conducting polymer polypyrrole doped with an
      oligonucleotide probe. Our goal was to develop a prototype electrochemical DNA
      sensor for detection of a biowarfare pathogen, variola major virus. The sensor
      has been optimized for higher specificity and sensitivity. It was possible to
      detect 1.6 fmol of complementary oligonucleotide target in 0.1 ml in seconds by
      using chronoamperometry. The sensitivity of the developed sensor is comparable to
      indirect electrochemical DNA sensors, which use electrochemical labels and
      reagent-intensive amplification. The developed sensing electrode is reusable,
      highly stable and suitable for storage in solution or in dry state.

PMID- 15967368
TI  - Electrochemically deposited chitosan hydrogel for horseradish peroxidase
      immobilization through gold nanoparticles self-assembly.
AB  - A new strategy for immobilization of horseradish peroxidase (HRP) has been
      presented by self-assembling gold nanoparticles on chitosan hydrogel modified Au
      electrode. From a mildly acidic chitosan solution, a chitosan film is
      electrochemically deposited on Au electrode surface via a negative voltage bias.
      This process is accompanied by the hydrogen evolution reaction, and the released
      hydrogen gas made the deposited chitosan film with porous structure, which
      facilitates the assembly of gold nanoparticles and HRP. The resulting substrates
      were characterized by atomic force microscopy (AFM) and electrochemical impedance
      spectroscopy (EIS). The immobilized HRP displayed an excellent catalytic property
      to the reduction of H2O2 in the presence of methylene blue mediator. The
      resulting biosensor (HRP-modified electrode) showed a wide dynamic range of 8.0
      microM-15 mM H2O2, and the linear ranges were 8.0 microM-0.12 mM and 0.50-12 mM,
      with a detection limit of 2.4 microM estimated at a signal-to-noise ratio of 3.
      Moreover, the biosensor remained about 85% of its original sensitivity after four
      weeks' storage.

PMID- 15967369
TI  - Intellectual property strategy in bioinformatics and biochips.
AB  - Intellectual property rights are essential in today's technology-driven age. A
      strong intellectual property protection strategy is crucial in the bioinformatics
      and biochips technology spaces as monetary and temporal resources are tremendous
      in finding a blockbuster drug or gene therapy, as well as in deploying advanced
      biosensor and other medical systems. Current problems and intellectual property
      practice in the genomic space are presented and analyzed. Various strategy and
      solutions are proposed to guide bioinformatic and biochip companies in forming an
      aggressive strategy to protect one's intellectual property and competitive
      positioning.

PMID- 15967370
TI  - Application of carbon nanotubes for detecting anti-hemagglutinins based on
      antigen-antibody interaction.
AB  - Carbon nanotube sensors detected anti-hemagglutinin binding to immobilized
      hemagglutinins. An ultra-sensitive detection method for antibodies or antigens in
      serum is required. Hemagglutinins were immobilized on the reverse side of a
      carbon nanotube, thereby producing a source and a drain. Electrode pads covered
      each edge of the nanotube. The I-V curves between the source and the drain were
      measured after incubation of anti-hemagglutinins with immobilized hemagglutinins
      in a buffered solution on the reverse side of the nanotube. The sensitivity of
      the CNT sensor was higher than that of an ELISA system. This method constitutes a
      new tool to analyze interaction among biomolecules on a substrate.

PMID- 15967371
TI  - Biosensor for the determination of phenols based on cross-linked enzyme crystals
      (CLEC) of laccase.
AB  - Cross-linked enzyme crystals (CLECs) are a versatile form of biocatalyst that can
      also be used for biosensor application. Laccase from Trametes versicolor
      (E.C.1.10.3.2) was crystallized, cross-linked and lyophilized with beta
      cyclodextrin. The CLEC laccase was found to be highly active towards phenols like
      2-amino phenol, guaiacol, catechol, pyrogallol, catechin and ABTS (non-phenolic).
      The CLEC laccase was embedded in 30% polyvinylpropylidone (PVP) gel and mounted
      into an electrode to make the sensor. The biosensor was used to detect the
      phenols in 50-1000 micromol concentration level. Phenols with lower molecular
      weight such as 2-amino phenol, catechol and pyrogallol gave a short response time
      where as the higher molecular weight substrates like catechin and ABTS had
      comparatively a long response time. The optimum pH of the analyte was 5.5-6.0
      when catechol was used as substrate. The CLEC laccase retained good activity for
      over 3 months.

PMID- 15967372
TI  - Encapsulation of glucose oxidase and an oxygen-quenched fluorophore in
      polyelectrolyte-coated calcium alginate microspheres as optical glucose sensor
      systems.
AB  - Microspheres coated with polyelectrolyte multilayers (PEM's) are being
      investigated for potential use as implantable biosensors-so-called "smart
      tattoos." In this work, the feasibility of this approach for glucose sensors was
      demonstrated by glucose oxidase encapsulated within calcium alginate
      microspheres, followed by entrapment of an oxygen-quenched ruthenium compound in
      the same microstructure. A novel feature of these microdevices is the formation
      of multilayer nanofilms on the surface of the microspheres, used to stabilize
      enzyme entrapment and control substrate diffusion. Confocal microscopy was used
      to confirm the stable encapsulation of sensor chemistry. The reversible response
      of sensors to step changes in glucose was observed, and preliminary experimental
      data were compared to theoretical predictions produced by a computational model.
      These findings demonstrate the promise of the described nanoengineering approach
      for production of functional implantable glucose sensor materials.

PMID- 15967373
TI  - Direct electron transfer between cytochrome P450scc and gold nanoparticles on
      screen-printed rhodium-graphite electrodes.
AB  - This paper is concerned with an investigation of electron transfer between
      cytochrome P450scc (CYP11A1) and gold nanoparticles immobilised on rhodium
      graphite electrodes. Thin films of gold nanoparticles were deposited onto the
      rhodium-graphite electrodes by drop casting. Cytochrome P450scc was deposited
      onto both gold nanoparticle modified and bare rhodium-graphite electrodes. Cyclic
      voltammetry indicated enhanced activity of the enzyme at the gold nanoparticle
      modified surface. The role of the nanoparticles in mediating electron transfer to
      the cytochrome P450scc was verified using ac impedance spectroscopy. Equivalent
      circuit analysis of the impedance spectra was performed and the values of the
      individual components estimated. On addition of aliquots of cholesterol to the
      electrolyte bioelectrocatalytic reduction currents were obtained. The sensitivity
      of the nanoparticle modified biosensor to cholesterol was 0.13 microA microM-1 in
      a detection range between 10 and 70 microM of cholesterol. This confirms that
      gold nanoparticles enhance electron transfer to the P450scc when present on the
      rhodium-graphite electrodes.

PMID- 15967374
TI  - Cloning and characterization of mouse homolog of the CXC chemokine receptor
      CXCR1.
AB  - CXCR2/IL-8RB was the only receptor previously reported in mice for ELR+ CXC
      chemokines, whereas the receptors for these chemokines in human include both
      CXCR1 and CXCR2. In this study, we cloned the full length cDNA of the mouse CXCR1
      (mCXCR1) gene. The deduced amino acid of mCXCR1 was 77% and 58% identical to the
      rat and human CXCR1, respectively. RT-PCR and Northern blot analysis showed that
      mCXCR1 mRNA was expressed in lung, spleen, thymus, peripheral blood leukocytes,
      as well as in the isolated neutrophils. In a mouse respiratory inflammation model
      induced by lipopolysaccharide, a large number of neutrophils infiltrated into the
      lung and, meanwhile, the mCXCR1 expression was significantly increased in the
      recruited neutrophils, suggesting that mCXCR1 may mediate the recruitment of
      neutrophils to the inflammation site under certain infections.

PMID- 15967375
TI  - Serum surfactant protein D is increased in acute and chronic inflammation in
      mice.
AB  - Surfactant protein A (SP-A) and surfactant protein D (SP-D) are important
      components of innate immunity that can modify the inflammatory response. However,
      alterations and regulation of SP-A and SP-D in acute and chronic inflammation are
      not well defined. In addition, serum SP-D may serve as a biomarker of lung
      inflammation. We determined the expression of SP-A and SP-D in murine models. To
      study acute inflammation, we instilled bleomycin intrabronchially. To study
      chronic lung inflammation, we used a transgenic mouse that overexpresses tumor
      necrosis factor (TNF)-alpha under the control of the SP-C promoter. These mice
      have a chronic mononuclear cell infiltration, airspace enlargement, pulmonary
      hypertension, and focal pulmonary fibrosis. In acute inflammation model, levels
      of mRNA for all surfactant proteins were reduced after bleomycin administration.
      However, serum SP-D was increased from days 7 to 28 after instillation. In
      chronic inflammation model, SP-D mRNA expression was increased, whereas the
      expression of SP-A, SP-B and SP-C was reduced. Both serum and lung SP-D
      concentrations were increased in chronic lung inflammation. These data clarified
      profile of SP-A and SP-D in acute and chronic inflammation and indicated that
      serum SP-D can serve as a biomarker of lung inflammation in both acute and
      chronic lung injury in mice.

PMID- 15967376
TI  - Decreased IgG production but increased MIP-1beta expression in collagen-induced
      arthritis in C-C chemokine receptor 5-deficient mice.
AB  - Collagen-induced arthritis (CIA) is a widely used model of human rheumatoid
      arthritis (RA) characterized by chronic inflammation of the synovial joints. The
      pathogenesis of RA and CIA has not been completely defined, but both involve the
      recruitment of leukocytes and lymphocytes to the joints and Th1-type cell
      mediated autoimmune responses. The C-C chemokine receptor 5 (CCR5) is
      preferentially expressed on Th1 cells and has been strongly implicated in
      inflammatory process through trafficking of leukocytes and lymphocytes into the
      sites of inflammation. We investigated the role of the CCR5 in CIA using CCR5
      knockout mice (CCR5-/-) in which we analyzed the consequences of CCR5 deficiency
      for the immune response and inflammation. We found that CCR5-/- mice showed a
      significant reduction in the incidence of CIA after collagen II (CII)
      immunization as compared to wild-type (CCR5+/+) mice. The reduced incidence seen
      in CCR5-/- mice was associated with these animals having significantly lower IgG
      levels, especially IgG2a and IgG2b antibodies against CII, as well as an
      obviously augmented IL-10 production in splenocytes. Overproduction of MIP-1beta
      in CCR5-deficient mice after CII-immunization may contribute partially to the
      occurrence of arthritis.

PMID- 15967377
TI  - From clinical evidence to molecular mechanisms underlying neuroprotection
      afforded by estrogens.
AB  - Recent studies have highlighted that female sex hormones represent potential
      neuroprotective agents against damage produced by acute and chronic injuries in
      the adult brain. Clinical reports have documented the effectiveness of estrogens
      to attenuate symptoms associated with Parkinson's disease, and to reduce the risk
      of Alzheimer's disease and cerebrovascular stroke. This evidence is corroborated
      by numerous experimental studies documenting the protective role of female sex
      hormones both in vitro and in vivo. Accordingly, estrogens have been shown to
      promote survival and differentiation of several neuronal populations maintained
      in culture, and to reduce cell death associated with excitotoxicity, oxidative
      stress, serum deprivation or exposure to beta-amyloid. The neuroprotective
      effects of estrogens have been widely documented in animal models of neurological
      disorders, such as Alzheimer's and Parkinson's diseases, as well as cerebral
      ischemia. Although estrogens are known to exert several direct effects on
      neurones, the cellular and molecular mechanisms implicated in their protective
      actions on the brain are not completely understood. Thus, on the basis of
      clinical and experimental evidence, in this review, we discuss recent findings
      concerning the neuronal effects of estrogens that may contribute to their
      neuroprotective actions. Both estrogen receptor-dependent and -independent
      mechanisms will be described. These include modulation of cell death regulators,
      such as Bcl-2, Akt and calpain, as well as interaction with growth factors, such
      as BDNF, NGF, IGF-I and their receptors. The anti-inflammatory effects of
      estrogens will also be described, namely their ability to reduce brain levels of
      inflammatory mediators, cytokines and chemokines. Finally, a brief overview about
      receptor-independent mechanisms of neuroprotection will aim at describing the
      antioxidant effects of estrogens, as well as their ability to modulate
      neurotransmission.

PMID- 15967378
TI  - Progressive loss of BDNF in a mouse model of Huntington's disease and rescue by
      BDNF delivery.
AB  - Huntingtin is a protein of 348 kDa that is mutated in Huntington's disease (HD),
      a dominantly inherited neurodegenerative disorder. Previous data have led us to
      propose that aspects of the disease arise from both a loss of the neuroprotective
      function of the wild-type protein, and a toxic activity gained by the mutant
      protein. In particular, we have shown that wild-type huntingtin stimulates the
      production of brain-derived neurotrophic factor (BDNF), a pro-survival factor for
      the striatal neurons that die in the pathology. Wild-type huntingtin controls
      BDNF gene transcription in cerebral cortex, which is then delivered to its
      striatal targets. In the disease state, supply of cortical BDNF to the striatum
      is strongly reduced, possibly leading to striatal vulnerability. Here we show
      that a reduction in cortical BDNF messenger level correlates with the progression
      of the disease in a mouse model of HD. In particular, we show that the
      progressive loss of mRNAs transcribed from BDNF exon II, III and IV follows a
      different pattern that may reflect different upstream mechanisms impaired by
      mutation in huntingtin. On this basis, we also discuss the possibility that
      delivery of BDNF may represent an useful strategy for Huntington's disease
      treatment.

PMID- 15967379
TI  - Prevention of cytosolic IAPs degradation: a potential pharmacological target in
      Huntington's Disease.
AB  - Huntington's Disease (HD) is a neurodegenerative disorder caused by an abnormally
      expanded polyglutamine trait in the amino-terminal region of huntingtin.
      Pathogenic mechanisms involve a gained toxicity of mutant huntingtin and a
      potentially reduced neuroprotective function of the wild-type allele. Among the
      molecular abnormalities reported, HD cells are characterized by the presence of
      aggregates, transcriptional dysregulation, altered mitochondrial membrane
      potential and aberrant Ca++ handling. In addition, upon exposure to toxic
      stimuli, increased mitochondrial release of cytochrome C and activation of
      caspase-9 and caspase-3 are found in HD cells and tissue. Here we report that
      HTRA2 and Smac/DIABLO, two additional mitochondrial pro-apoptotic factors, are
      aberrantly released from brain-derived cells expressing mutant huntingtin. This
      event causes a reduction in levels of the cytosolic IAP1 (Inhibitor of Apoptosis
      Protein-1) and XIAP (X-linked inhibitor apoptosis) antiapoptotic IAP family
      members. Reduced IAP levels are also found in post-mortem HD brain tissue.
      Treatment with ucf101, a serine protease HTRA2 specific inhibitor, counteracts
      IAPs degradation in HD cells and increases their survival. These results point to
      the IAPs as potential pharmacological targets in Huntington's Disease.

PMID- 15967380
TI  - The effect of fluvoxamine on ouabain-induced arrhythmia in isolated guinea-pig
      atria.
AB  - The effect of fluvoxamine (FLV) a selective serotonin reuptake inhibitor agent
      was studied on ouabain-induced arrhythmia in spontaneously beating isolated
      guinea-pig atria. FLV (8-64 microM) caused a dose-dependent decrease in the rate
      of contractions (7-52%) and in the contractile force (11-57%). Ouabain alone (2
      microM) produced arrhythmia at 4.6 min and asystole at 17.4 min. Pre
      administration of the atria with FLV (32 microM) significantly increased the time
      required to produce arrhythmia by ouabain to 14.6 min, prolonged the beating of
      atria to more than 58.6 min and delayed the occurrence of asystolia. The pattern
      of contractile force induced by FLV+ouabain was more regular than that produced
      by ouabain alone. These findings indicate that FLV produces direct cardiac
      action, probably due to the inhibition of cardiac Na+ and Ca2+ channels. Our
      results suggest that FLV may reduce the membrane conduction through inhibition of
      ionic channels which decrease ouabain-induced arrhythmia.

PMID- 15967381
TI  - Regulation of Ca2+ movements by cyclovirobuxine D in ECV304 endothelial cells.
AB  - In Fura-2/loaded ECV304 endothelial cells cyclovirobuxine D promoted a transient
      increase in cytosolic free Ca2+ originating from both an intracellular pool
      sensitive to the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin and the
      extracellular space. The intracellular pool was apparently different from that
      mobilized by other agents acting through IP3 generation. The integrity of the
      plasma membrane was an absolute requirement. In cells treated with digitonin,
      cyclovirobuxine D did not promote any Ca2+ release from the intracellular stores
      even at high concentrations and in the absence or presence of thapsigargin or
      sodium azide, the inhibitors of the endoplasmic reticular or mitochondrial Ca2+
      uptake. Furthermore, cyclovirobuxine D was effective in halting the persistent
      increase in cytosolic Ca2+ caused by thapsigargin, inhibiting the operation of
      the "capacitative" Ca2+ membrane channels as demonstrated by the decrease in the
      extent of both Ca2+-overshoot and Mn2+ influx. Additional effects of
      cyclovirobuxine D included a depolarization of plasma membrane apparently related
      to an enhanced influx of Na+ from the extracellular space. The results obtained
      indicate that cyclovirobuxine D markedly affects intracellular Ca2+ homeostasis
      in ECV304 endothelial cells by both promoting a discharge of intracellular pools
      and by interfering with the operation of store-dependent channels via plasma
      membrane depolarization.

PMID- 15967382
TI  - Antioxidative and anti-inflammatory effects of repaglinide in plasma of diabetic
      animals.
AB  - Oxidative stress, defined as an imbalance between the production of reactive
      oxygen species (ROS) and antioxidant defense, is considered to be an important
      pathogenic factor in diabetes mellitus and its complications. In diabetic state,
      ROS might also be implicated in promoting a state of systemic inflammation.
      Recently, it was demonstrated that antioxidant therapy could be used to stop the
      initiation and propagation of this inflammatory response. Repaglinide is a new
      oral antidiabetic agent with a possible antioxidant activity. Therefore, in the
      present study, a possible therapeutic value of repaglinide in ameliorating the
      oxidative and inflammatory processes was tested in diabetic animals. In the
      study, the levels of total antioxidant status (TAS), ascorbic acid (AA), protein
      carbonyl groups (PCG) and interleukin-6 (IL-6) were determined in plasma of
      diabetic rabbits after 4 and 8 weeks of repaglinide treatment (1mg daily). Ex
      vivo analysis revealed that there were significant differences in these markers
      between hyperglycemic and control animals (P<0.05). Some of these parameters were
      ameliorated by repaglinide treatment. In diabetic rabbits treated with
      repaglinide, protein oxidation was diminished by 17.8% after 8 weeks of
      experiment. The level of AA in plasma of diabetic treated animals was higher than
      in non-treated diabetic groups (by 9.4 and 22.6% after 4 and 8 weeks,
      respectively). In diabetic treated animals, the TAS level was also significantly
      increased (by 23.6 and 16.7%). However, in diabetic rabbits, repaglinide did not
      affect the concentration of IL-6.

PMID- 15967383
TI  - Combined effects of protein kinase inhibitors and 5-fluorouracil on CEA
      expression in human colon cancer cells.
AB  - Previous studies showed that 5-fluorouracil (5-FU) and Staurosporine (ST), a
      protein kinase inhibitor (PKI), were able to increase the expression of
      carcinoembryonic antigen (CEA) in human colon cancer cells. In the present study,
      we examined the in vitro effects of five PKIs, i.e. ST, 1-5-isoquinolinyl
      sulfonyl-2-methylpiperazine (H-7), bisindolylmaleimide-I (BIS), Genistein (GEN),
      and Herbimycin A (HERB) alone or in combination with 5-FU on CEA expression. C22
      20, a clonal subline, derived from colon cancer HT-29 line, selected for low
      expression of CEA, was used in our experimental model. Among the PKIs tested,
      only ST, at non-toxic concentrations of 5 nM, was capable of increasing the level
      of CEA. The other PKIs did not modify CEA expression when used either alone or in
      combination with 5-FU. Flow cytometric analysis showed that treatment of cells
      with 5-FU + ST resulted in a synergistic increase of CEA expression, being higher
      than that obtainable with both agents alone. Moreover, the increase of CEA
      expression occurred not only in membrane fractions but also in cytosolic
      compartments, as indicated by Western blot analysis. The present study suggests
      that ST-mediated induction of CEA expression in cancer cells is PKC independent
      and could be of potential clinical interest for the development of new diagnostic
      and/or immunotherapeutic approaches.

PMID- 15967384
TI  - Protective effects of icariin on human umbilical vein endothelial cell injury
      induced by H2O2 in vitro.
AB  - Icariin is a flavonoid isolated from Epimedium and is considered to be the major
      pharmacological active component of Epimedii Herba. In the present investigation,
      we studied and confirmed the protective activity of icariin on H2O2-induced
      injury in human umbilical vein endothelial cell line: ECV-304. Eighteen-hour
      treatment with 750 micromol l(-1) H2O2 significantly decreased the viability of
      ECV-304 cells, which was accompanied with apparent apoptotic features, including
      distinct cell morphological alteration and the increase of caspase-3 expression.
      In addition, it is observed that H2O2 increased the amounts of malondialdenhyde
      (MDA) and the dehydrogenase (LDH), and decreased the content of nitric oxide (NO)
      in ECV-304 cells. However, pretreatment with 0.1-50 micromol l(-1) icariin
      resulted in a significant recovery from H2O2-induced cell apoptosis. Also, it
      decreased other H2O2-induced damage in a concentration-dependent manner.
      Furthermore, pretreatment with icariin decreased the expression of caspase-3,
      which was known to be involved as a key role executor in H2O2-induced cell
      apoptosis. The endothelial cells apoptosis were detected by acridine
      orange/ethidium bromide (AO/EB) dual staining as well as flow cytometry, and the
      expression of pro-apoptotic factor caspase-3 were detected by immunocytochemical
      method. Taken together, these data suggest that protective effects of icariin
      against oxidative injuries of ECV-304 cells may be achieved via decreasing of
      caspase expression.

PMID- 15967385
TI  - Differential effects of eicosapentaenoic and docosahexaenoic acids upon oxidant
      stimulated release and uptake of arachidonic acid in human lymphoma U937 cells.
AB  - The use of n-3 polyunsaturated fatty acids, as found in fish-oil derived dietary
      supplements, as anti-inflammatory agents is supported by a variety of biochemical
      and physiological data. Recent studies investigating the therapeutic potential of
      long chain (>C20) n-3 fatty acids in mental illness have lead to the conclusion,
      however, that not all n-3 fatty acid types are equally efficacious. In particular
      eicosapentaeoic acid (EPA) appears to possess antidepressant and antipsychotic
      activity, while docosahexaenoic acid (DHA) does not, an effect suggested to be
      due to a differential ability to antagonize arachidonic acid (AA)-dependent cell
      signalling. In this study, we examine the effect of EPA and DHA supplementation
      upon uptake and release of arachidonic acid stimulated by tert-butyl
      hydroperoxide/Fe2+ in U937 cells. Oxidant-stimulated 3H-AA release from cells was
      enhanced by pre-treatment with EPA, DHA and AA, but not stearic or oleic acids
      for 18 days, with the order of effect magnitude being EPA > DHA = AA.
      Supplementation of cells for 1 day gave qualitatively similar results, although
      the effect magnitude was smaller. To determine whether enhanced release was due
      to decreased reuptake of AA, cells were cultured in the presence of 10 microM
      fatty acids. Pre-treatment of cells with EPA, and to a lesser extent AA, but not
      DHA, inhibited uptake of 3H-AA measured subsequent to the removal of unesterified
      fatty acids. This study suggests that, in U937 cells, EPA can alter the rate of
      uptake and release of AA from phospholipids in an exposure time-dependent manner,
      whereas DHA has no or little effect. Our results predict that EPA will have a
      more pronounced effect upon AA-dependent processes compared to DHA, and suggests
      that the relative amounts of EPA and DHA in fish oil supplements may modify their
      biochemical, and potentially, behavioural effects.

PMID- 15967386
TI  - Tempol reduces reperfusion-induced arrhythmias in anaesthetized rats.
AB  - The generation of reactive oxygen species (ROS) contributes to reperfusion
      induced arrhythmias. In the present study, the antiarrhythmic effects of tempol
      and tiron, two membrane-permeable radical scavengers, on reperfusion-induced
      arrhythmias in rats in vivo were investigated. The anaesthetized rats were
      subjected to 5 min of left descending coronary artery (LAD) occlusion followed by
      30 min of reperfusion. All rats pretreated with saline developed ventricular
      tachycardia (VT) and ventricular fibrillation (VF) at the onset of reperfusion,
      and most of the rats died from irreversible VF at the end of reperfusion.
      However, pretreatment with tempol (30 or 100 mg kg(-1)) 5 min before reperfusion
      reduced mortality, arrhythmia score and the incidence and duration of VT and VF.
      In the rats pretreated with high dose of tempol (100 mg kg(-1)), no VF happened
      and all rats were alive at the end of the experiment. The arrhythmia score was
      also significantly decreased compared with that of rats pretreated with saline
      (0.80 +/- 0.4 versus 5.6 +/- 0.4, P < 0.01). Tiron also provided nearly complete
      protection against reperfusion-induced arrhythmias when given 2 min before
      reperfusion. On the other hand, intravenous administration of tempol induced
      decreases in mean arterial pressure (MAP), heart rate (HR) and pressure rate
      index (PRI), a relative indicator of myocardial oxygen consumption. In order to
      determine whether the antiarrhythmic effects of tempol were secondary to the
      reduction of myocardial oxygen consumption, continuous electrical stimulation of
      the aortic depressor nerve (3 V, 10 ms and 10 Hz) was carried out in a group of
      rats to induce decreases in MAP, HR and PRI similar to those in the high dose of
      Tempol group. However, these rats did not show significant changes in the
      severity of reperfusion-induced arrhythmias. We conclude that both tempol and
      tiron significantly reduce reperfusion-induced arrhythmias in rats, and this
      protective action is independent of hemodynamic effects.

PMID- 15967387
TI  - A positive or a negative confounding variable? A simple teaching aid for
      clinicians and students.
AB  - Anticipating the direction of a confounding variable can be problematic
      especially to introductory students. Using elementary rules of mathematics, we
      describe below a simple instructional tool for deriving the direction of
      confounding bias. The tool is illustrated with examples and a heuristic
      mathematical justification is also described.

PMID- 15967388
TI  - Regarding "Increase in breast cancer incidence in middle-aged women during the
      1990s".

PMID- 15967390
TI  - Case definition in epidemiologic studies of AD/HD.
AB  - PURPOSE: Propose a five-step multigating, multimodal procedure for research case
      definition and identification of attention-deficit/hyperactivity disorder (AD/HD)
      in population-based epidemiologic studies. METHODS: Subjects included a birth
      cohort of all children born between 1976 and 1982 who remained in Rochester after
      age 5. Screening for AD/HD required 4 steps, using these sources: school/medical
      records, computerized diagnostic index, and private psychiatry records. In step
      5, research criteria were applied to potential cases. The model for defining
      cases used combinations of three categories of information (DSM-IV,
      questionnaire, clinical diagnosis). Validity was tested by comparing medication
      treatment, substance abuse, school outcomes, and comorbidities between cases who
      did or did not meet DSM-IV criteria. RESULTS: Among 5718 subjects, 1344 potential
      cases were identified; 379 met research criteria. No difference in gender,
      treatment, school outcome, or professional making clinical diagnoses was found
      between cases who did (N=228) and did not (N=151) meet DSM-IV criteria. However,
      cases not meeting DSM-IV criteria were more inattentive (33.8% vs. 17.1%; p <
      0.001), older (age 12.8 vs. 10.5 years; p=0.01), with less substance abuse (15.2%
      vs. 26.3%; p < 0.001) and psychiatric comorbidities (43.1% vs. 54.4%; p=0.031).
      CONCLUSIONS: If only DSM-IV criteria were applied, 151 cases would not have been
      identified. This study underscores the importance of using multiple sources and
      combinations of documented information for case definition and identification.

PMID- 15967391
TI  - Early age at menarche and allostatic load: data from the Third National Health
      and Nutrition Examination Survey.
AB  - PURPOSE: To examine whether there is an association between early age at menarche
      and allostatic load-a measure of cumulative biologic risk-using data from the
      Third National Health and Nutrition Examination Survey (NHANES III). METHODS: A
      total of 2470 (weighted N=25,544,838) women aged between 17 and 30 years with
      interview and examination data who did not report oral contraceptive use before
      menarche and were not missing data on the exposure or outcome were included.
      Early menarche was defined as menarche at age 10 or younger. The allostatic load
      score was the sum of the number of 11 components for which an individual had a
      value within the high-risk range. RESULTS: The prevalence of early menarche was
      7%. Although the overall allostatic load scores were low when compared with older
      adults, the mean allostatic load score was higher among those with menarche at
      ages 10 or younger compared with those with later ages at menarche (1.99 vs.
      1.33). After adjusting for age, race/ethnicity, level of education, household
      poverty income ratio, smoking, and depression history, women with high allostatic
      load scores had more than 2 times the odds as those with low scores of
      experiencing menarche at age 10 or earlier (OR=2.18; 95% CI, 1.29-3.68).
      CONCLUSIONS: This study is the first to report and examine the relationship
      between age at menarche and allostatic load. Future studies involving prospective
      measurement of allostatic load biomarkers may prove essential for disentangling
      the association between allostatic load and early age at menarche.

PMID- 15967392
TI  - Smoking trajectories of adolescent novice smokers in a longitudinal study of
      tobacco use.
AB  - PURPOSE: To describe longitudinal trajectories of smoking intensity in adolescent
      novice smokers and to identify predictors of trajectory class membership.
      METHODS: Cigarette consumption among 369 novice smokers (mean age 13 years) was
      measured over a mean 24 months of follow-up after smoking onset. Classes of
      smoking intensity trajectories were identified using latent class growth
      modeling. Predictors of trajectory class membership were identified in polytomous
      logistic regression. RESULTS: There was considerable between-subject
      heterogeneity in individual trajectories over time. Four classes of smoking
      intensity trajectories were identified: low-intensity, non-progressing smokers
      (72.4% of subjects), and slow, moderate, and rapid escalators (11.1%, 10.8%, and
      5.7% of subjects, respectively). Gender, poor academic performance, and having
      more than half of friends who smoke at smoking onset independently predicted
      development of trajectory pattern. Escalating trajectory patterns were associated
      with earlier development of nicotine dependence and tolerance. CONCLUSIONS:
      Cigarette consumption will not escalate rapidly among three-quarters of
      adolescent novice smokers. Novice smokers who do escalate rapidly should be
      targeted for early tobacco control intervention to prevent development of
      nicotine dependence and sustained smoking.

PMID- 15967393
TI  - Assessment of smoking behaviors in the home and their influence on children's
      passive smoking: development of a questionnaire.
AB  - PURPOSE: To construct and validate a questionnaire aiming to measure children's
      exposure to environmental tobacco smoke (ETS) in the home. METHODS: The
      development of the instrument included epidemiological studies, qualitative
      interviews, pilot studies, and validation with biomarkers and is described in
      seven consecutive steps. Parents of preschool children, from different population
      based samples in south-east Sweden, have participated in the studies. RESULTS:
      Content and face validity was tested by an expert panel and core elements for the
      purpose of the instrument identified. Reliability was shown with test-retest of
      the first version. The validation with biomarkers indicated that the sensitivity
      of the instrument was high enough to discriminate between children's ETS exposure
      levels. Cotinine/creatinine levels were related to parents' described smoking
      behaviors. Differences were shown between children from non-smoking homes, and
      all groups with smoking parents, independent of their smoking behavior (p <
      0.01), as well as between parents smoking strictly outdoors and parents reporting
      indoor smoking (p < 0.001). CONCLUSION: The results indicate that the presented
      instrument can be used to discriminate between different levels of ETS exposure
      and when children's level of tobacco smoke exposure is to be assessed.

PMID- 15967394
TI  - Caffeine metabolism, genetics, and perinatal outcomes: a review of exposure
      assessment considerations during pregnancy.
AB  - PURPOSE: To review the methodologic issues complicating caffeine exposure
      assessment during pregnancy; to discuss maternal and fetal caffeine metabolism,
      including genetic polymorphisms affecting caffeine metabolism; and to discuss the
      endogenous and exogenous risk factors known to influence caffeine metabolism.
      METHODS: A review of the relevant literature. RESULTS: There is wide inter
      individual variation in caffeine metabolism, primarily due to variations in
      CYP1A2 enzyme activity. Some variability in CYP1A2 activity is due to genetic
      polymorphisms in the CYP1A2 gene which can cause increased or decreased
      inducibility of the enzyme. Considerable evidence exists that maternal caffeine
      metabolism is influenced by a variety of endogenous and exogenous factors and
      studying the genetic polymorphisms may improve understanding of the potential
      effects of caffeine and its metabolites on perinatal outcomes. There is
      substantial evidence that measurement of maternal, fetal, and neonatal caffeine
      metabolites may allow for a more precise measure of fetal caffeine exposure.
      CONCLUSIONS: Research on the genetic polymorphisms affecting caffeine metabolism
      may further explain the potential effects of caffeine and its metabolites on
      perinatal outcomes.

PMID- 15967395
TI  - Multilayer assembly of calf thymus DNA and poly(4-vinylpyridine) derivative
      bearing [Os(bpy)(2)Cl](2+): redox behavior within DNA film.
AB  - Polyelectrolyte multilayer (PEM) films containing polycationic osmium (Os)
      bipyridyl (bpy) complex-attached poly(4-vinylpyridine) (PVP) derivative
      [Os(bpy)(2)Cl](2+)-PVP (Os-PVP) and polyanionic calf thymus DNA (CT-DNA) on the
      surface of gold (Au) electrodes were prepared using a layer-by-layer self
      assembly method, and their redox properties were studied. Os complex shows
      different redox behavior with CT-DNA film in comparison with other PEM film which
      is composed of ordinary polymers. A cyclic voltammetric study suggested that the
      outermost polyanionic DNA layer does not hinder the redox reaction of Os complex
      within the Os-PVP/CT-DNA multilayer film, which may be helpful to understand the
      electron transfer mechanism with the DNA film. For all the Os-complex-containing
      PEM layers studied, a diffusion-free electron transfer from the Os complex
      moieties in these films to the electrode surface was observed. An
      electrocatalytic oxidation of ascorbic acid (AA) by this DNA-containing PEM film
      covered electrode was also proposed.

PMID- 15967396
TI  - Electrochemical oxidation of 2-thiouracil at pyrolytic graphite electrode.
AB  - 2-Thiouracil has been studied in phosphate buffers of pH 1.95-11.08 using linear
      and cyclic sweep voltammetry, coulometry, controlled potential electrolysis and
      spectral studies. One well-defined oxidation peak I(a) in the pH range 1.95-11.08
      was noticed. The number of electrons involved in peak I(a) was found to be four
      in a thin layer cell whereas under exhaustive electrolysis condition oxidation
      was found to involve six electrons. A reduction peak II(c) (2e, 2H(+)) is noticed
      in the reverse sweep. Spectral studies during oxidation were carried out at
      different pH. Kinetic studies indicated that the decay of the UV-absorbing
      intermediate is a first order reaction. The products of the electrooxidation have
      been characterized and a tentative EC mechanism has been suggested for the
      oxidation of 2-thiouracil.

PMID- 15967397
TI  - Covalent attachment of glucose oxidase to an Au electrode modified with gold
      nanoparticles for use as glucose biosensor.
AB  - A feasible method to fabricate glucose biosensor was developed by covalent
      attachment of glucose oxidase (GOx) to a gold nanoparticle monolayer modified Au
      electrode. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy
      (EIS) of ferrocyanide followed and confirmed the assemble process of biosensor,
      and indicated that the gold nanoparticles in the biosensing interface efficiently
      improved the electron transfer between analyte and electrode surface. CV
      performed in the presence of excess glucose and artificial redox mediator,
      ferrocenemethanol, allowed to quantify the surface concentration of electrically
      wired enzyme (Gamma(E)(0)) on the basis of kinetic models reported in literature.
      The Gamma(E)(0) on proposed electrode was high to 4.1 x 10(-12) mol.cm(-2), which
      was more than four times of that on electrode direct immobilization of enzyme by
      cystamine without intermediate layer of gold nanoparticles and 2.4 times of a
      saturated monolayer of GOx on electrode surface. The analytical performance of
      this biosensor was investigated by amperometry. The sensor provided a linear
      response to glucose over the concentration range of 2.0 x 10(-5)-5.7 x 10(-3) M
      with a sensitivity of 8.8 microA.mM(-1).cm(-2) and a detection limit of 8.2
      microM. The apparent Michaelis-Menten constant (K(m)(app)) for the sensor was
      found to be 4.3 mM. In addition, the sensor has good reproducibility, and can
      remain stable over 30 days.

PMID- 15967398
TI  - Investigation of novel mediators for a glucose biosensor based on metal
      picolinate complexes.
AB  - The metal complexes [Os(byp)(2)(pic)](+) and [Ru(byp)(2)(pic)](+) where byp is
      2,2'-bipyridine and HPic is o-picolinic acid were synthesised and characterised
      using spectroscopic and electrochemical techniques. These complexes were then
      evaluated as mediators for a glucose oxidase (GOx)-based biosensor. Results
      demonstrate the electrocatalytic behaviour of both metal couples towards
      regeneration of the flavoprotein GOx (FADH(2)) group, when co-immobilised with
      glucose oxidase. Surface immobilisation was achieved by potential cycling in
      aqueous solutions of the metal complexes at a glucose oxidase (GOx)/Nafion
      modified electrode. This proved successful in terms of catalytic efficiency and
      stability of redox sites. Kinetic parameters associated with both enzymatic and
      mediator reactions were estimated and the stability/performance properties of the
      sensor were tested.

PMID- 15967399
TI  - Local and transient structural changes in stratum corneum at high electric
      fields: contribution of Joule heating.
AB  - Electroporation of skin is accompanied by local heating, such that thermally
      induced structural changes of the stratum corneum (SC) accompany the field
      effect. Comparing on the time scale, the local changes in structure, temperature
      and conductance of the SC, during and after the pulse, it is seen that Joule
      heating also facilitates the subsequent molecular transport. It is found that the
      transport of medium-sized, ionic molecules occurs through localized transport
      regions (LTR). The size of a LTR increases with the pulse length, whereas the
      density of the LTRs increases with increasing voltage, for instance at U(SC=)80
      V, the LTR cover approximately 0.02--1% of the surface area. The state of low
      resistance within the LTR is long-lived. During high voltage application, the
      center of the LTR is heated above the phase transition temperature of the SC
      lipids (70 degrees C) and the heat front propagates outwards. Inside the SC, the
      pulse causes aggregates of small-sized vesicles. At a higher temperature, the
      aggregate formation and their disappearance are delayed. Multiple pulses with the
      applied voltage of U(appl)=80 V induce the formation of long-lasting vesicle
      aggregates with a diameter of slashed circle=1--30 microm, covering 0.05--0.5% of
      the total sample area. The electric energy dissipated within the LTR during high
      voltage application is apparently sufficient to raise the temperature well above
      the phase transition temperature of the lipids of the SC, accounting for the
      conformational changes from the multi-lamella to the vesicular structures.

PMID- 15967400
TI  - Novel electrochemical sensor system for monitoring metabolic activity during the
      growth and cultivation of prokaryotic and eukaryotic cells.
AB  - A novel amperometric sensor system is presented which directly reflects the
      metabolic activity of prokaryotic and eukaryotic cells during cultivation. The
      principle of an externally mounted sensor is current measurement using a three
      electrode system. Only living cells are detected since the current signal is
      based on a redox mediator. Added to a culture sample in its oxidized form, the
      mediator is reduced by cellular metabolism and subsequently re-oxidized at the
      anode. The spontaneous immobilisation of the cells in the reaction vessel of the
      sensor by swelling dextrane polymers (Sephadex) prior to measurement is the key
      to a fast, consistent signal. Even metabolically less active mammalian cells
      produce a reliable signal within a few minutes; this may open up future
      applications of the electrochemical sensor in closed loop process control not
      only for bacterial and fungal bioprocesses, but also in cell culture technology.

PMID- 15967401
TI  - Transmembrane voltage induced on a cell membrane in suspensions exposed to an
      alternating field: a theoretical analysis.
AB  - We present analytical equations for the transmembrane voltage (DeltaPsi) induced
      by an alternating field on spherical cells arranged in orderly suspensions. For
      physiologically normal cells, the cell membrane was assumed to be non-conductive.
      With increasing alternating field frequency, capacitive property of the cytoplasm
      and the external medium become increasingly important and thus must be accounted
      for. Considering the symmetry of the arrayed cells and the tiny volume of the
      unit cell compared to that of the suspensions, the influence exerted on a unit
      cell by other cells was posited to be approximately symmetrical with respect to
      the symmetrical axis. This implies that the shape of the equipotential plane of
      spherical cells in the suspensions is similar to that of the single cell exposed
      to the external field, though the value of the potential of both cells should be
      different. Therefore, the internal field of the cytoplasm and the equivalent body
      of a unit cell in the suspensions should be approximately constant. This allows
      for calculating the effective average field in the equivalent body with Maxwell
      Wagner and Bruggeman-Hanai equations for low and high cell concentrations,
      respectively. We investigated the conditions, under which the local electric
      field of a unit cells in suspension is approximately equal to that of a single
      cell. Under these conditions the analytical solution for DeltaPsi induced by
      alternating fields on cells in suspensions can be derived from that of the single
      cell.

PMID- 15967402
TI  - Surface contact measurement of electrical cell uncoupling in the mouse heart
      during ischemia.
AB  - Electrical cell uncoupling via gap junction closure is assumed to cause
      characteristic changes of the passive dielectric spectrum of ischemic heart
      tissue. In order to find an independent evidence for this assumption, we analysed
      heart tissue during ischemia, measured the open state of gap junctions by means
      of dye transfer and correlated this parameter with the time course of the
      dielectric permittivity. The hearts were pre-ischemically arrested by perfusion
      with Ringer solution containing 20 mmol/L of potassium (group KCL, n=10). This
      solution was also used with the addition of two gap junction blockers, either 3
      mmol/L heptanol (group HEP, n=4) or 20 micromol/L palmitoleic acid (group PA,
      n=7). During subsequent ischemia at 21.0+/-0.5 degrees C, we monitored the
      passive dielectric permittivity spectrum and the spread of dye. After a sigmoidal
      increase the dielectric permittivity reached an upper plateau at 61+/-22 min of
      ischemia in KCL, at 45+/-7 min in PA, and already during perfusion at 2+/-1 min
      in group HEP. At the beginning of ischemia, dye migrated to neighbouring cells in
      groups KCL and PA but not in HEP. In KCL and PA, the intercellular diffusion of
      dye stopped after 64+/-26 and 40+/-11 min of ischemia, respectively. Our results
      suggest that the sigmoidal increase in dielectric permittivity and the reduction
      of dye diffusion depend on a common mechanism, namely gap junction closure.

PMID- 15967403
TI  - The interaction of cysteine with chromium(VI) ions under UV irradiation.
AB  - In 0.1 M phosphate buffer (pH 7.2), the interaction of chromium(VI) with cysteine
      in the presence and absence of UV irradiation was studied by cyclic voltammetry
      and electronic spectroscopy techniques. The reduction of Cr(VI) by cysteine takes
      place through the formation of Cr(VI)-thioester intermediate. On the cyclic
      voltammograms of cysteine and Cr(VI) mixture, the peaks at -0.315 and -0.800 V
      were observed, and these peaks are corresponding to the reduction of Cr(VI)
      thioester and thiyl radical, respectively. In the cysteine solution exposed to UV
      irradiation, the formation of free cystine was observed at -0.792 V. In the
      cysteine and Cr(VI) mixture exposed to UV irradiation, the peak current of thiyl
      radical increases while the peak current of Cr(VI)-thioester reaches a maximum at
      15 min and then decreases by increasing UV irradiation time. The formation of the
      thioester in the reaction between Cr(VI) and cysteine in aqueous media has been
      studied by monitoring the decrease of Cr(VI) at 370 nm. It was observed that the
      reaction is catalyzed by the UV irradiation of the Cr(VI) and cysteine mixture.

PMID- 15967404
TI  - Changes of the solution pH due to exposure by high-voltage electric pulses.
AB  - The change of the pH of a NaCl solution (139-149 mM NaCl) buffered with 5-15 mM
      sodium phosphates (pH 7.4) during electromanipulation was studied. It has been
      determined that an increase in the pH value of electroporation solution of a
      whole chamber volume, caused by the application of electric field pulses,
      commonly used in cell electromanipulation procedures, can exceed 1-2 pH units.
      Several materials for the cathode were tested. In all cases a stainless steel
      anode was utilized. The aluminum cathode gave a two-fold greater DeltapH in
      comparison with platinum, copper or stainless steel cathodes. In addition, a
      substantial release of aluminum (up to 1 mg/l) from the cathode was observed. It
      has also been found that the shift in pH depended on the medium conductivity:
      DeltapH of the solution, in which sucrose was substituted for NaCl, was about 5
      times less. On the basis of the results obtained here, to avoid the plausible
      undesirable consequences of the cathodic electrolysis processes, in particular
      under the conditions of strong electric treatment, it could be recommended that
      chambers with aluminum electrodes not be utilized and one should use strongly
      buffered solutions of low conductivity and alternating current (sine or square
      wave) bipolar electric pulses.

PMID- 15967405
TI  - Using source cues and familiarity cues to resist imagination inflation.
AB  - To investigate whether people can resist imagination inflation--the imagination
      induced increased confidence that fictitious childhood events really happened--we
      gave them different types of cues. In a three-stage procedure, participants: (1)
      rated their confidence that a list of childhood events had happened to them, (2)
      imagined some of these events, and (3) made confidence ratings a second time.
      Subjects received either no cues about the source of the imagined event, an
      additional source cue (perspective), an additional familiarity cue (a
      plausibility questionnaire), or both cues. Only subjects who had both types of
      cues resisted imagination inflation. These results suggest that additional cues
      can sometimes safeguard people from becoming more confident that fictitious
      events were genuine experiences.

PMID- 15967406
TI  - PCR-RFLP of mitochondrial cytochrome oxidase subunit II and ITS2 of ribosomal
      DNA: markers for the identification of members of the Anopheles culicifacies
      complex (Diptera: Culicidae).
AB  - Anopheles culicifacies Giles is a complex of five sibling species, provisionally
      designated as species A, B, C, D and E. Species A, C, D and E are vectors of
      malaria in India. Species A, B, C and D can be identified by polytene chromosome
      examination except in areas where species B and E are sympatric. Species B and E
      share the same configuration of the polytene chromosomes but can be
      differentiated by examining the mitotic chromosomes of F(1) progeny from field
      collection. Further, polytene chromosome examination method requires the
      mosquitoes to be at the semigravid stage, which limits on use of this method to a
      very small proportion of the population. The present study investigated whether
      the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method can be used to differentiate the members of this complex. Complete ITS2
      region along with part of the 5.8S and 28S rDNA sequences (512 bp) and the
      mitochondrial cytochrome oxidase II (530 bp) were amplified and digested with
      different restriction endonucleases. The Alu I digest of the COII amplicon and
      Rsa I digest of the ITS2 amplicon could distinguish two categories: species A and
      D forming one category and species B, C and E forming another. Further, Dde I
      digestion of the COII amplicon could distinguish species E from species B and C
      within the latter category. The PCR-RFLP techniques developed in this study can
      be applied to areas where species A and B and species B and E are sympatric.

PMID- 15967408
TI  - High activity of mitochondrial glycerophosphate dehydrogenase and
      glycerophosphate-dependent ROS production in prostate cancer cell lines.
AB  - Most malignant cells are highly glycolytic and produce high levels of reactive
      oxygen species (ROS) compared to normal cells. Mitochondrial glycerophosphate
      dehydrogenase (mGPDH) participates in the reoxidation of cytosolic NADH by
      delivering reducing equivalents from this molecule into the electron transport
      chain, thus sustaining glycolysis. Here, we investigate the role of mGPDH in
      maintaining an increased rate of glycolysis and evaluate glycerophosphate
      dependent ROS production in prostate cancer cell lines (LNCaP, DU145, PC3, and
      CL1). Immunoblot, polarographic, and spectrophotometric analyses revealed that
      mGPDH abundance and activity was significantly elevated in prostate cancer cell
      lines when compared to the normal prostate epithelial cell line PNT1A.
      Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS
      production was increased 1.68- to 4.44-fold and 5- to 7-fold, respectively, in
      prostate cancer cell lines when compared to PNT1A cells. Overall, these data
      demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and
      is an important site of electron leakage leading to ROS production in prostate
      cancer cells.

PMID- 15967407
TI  - Differentiation of pluripotent C3H10T1/2 cells rapidly elevates CYP1B1 through a
      novel process that overcomes a loss of Ah Receptor.
AB  - Stimulation of C3H10T1/2 cells by an adipogenic hormonal mixture (IDM) consisting
      of insulin (I), dexamethasone (D), and methylisobutylxanthine (M) substantially
      induces cytochrome P450 (CYP) 1B1 expression. This stimulation represents up to
      40% of the level produced by maximum activation of the arylhydrocarbon receptor
      (AhR) with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dexamethasone and
      methylisobutylxanthine in combination produced near maximum elevation of CYP1B1
      along with a subsequent decline in AhR that paralleled the rise in peroxisome
      proliferator-activated receptorgamma1 (PPARgamma1). Inhibitors of AhR activity,
      which block TCDD induction, did not affect this increase of CYP1B1 expression,
      which was, therefore, independent of AhR activity. These responses were
      unaffected by inhibition of DNA synthesis, which was required for PPARgamma1
      induction and terminal differentiation. Induction of CYP1B1 mRNA was paralleled
      by increased CYP1B1 promoter-luciferase reporter activity. The initial 0.8kb of
      promoter region, which was sufficient for 24h near maximum stimulation, did not
      contain either the key AhR-responsive elements that mediate the TCDD response or
      CREB and SF1 elements that mediate cAMP stimulation of rat CYP1B1 in
      steroidogenic cells. This reporter response to IDM stimulation, but not to TCDD,
      was maintained in AhR-null fibroblasts. CYP1B1 expression, unlike TCDD induction,
      was stimulated by IDM in only about half the cells. CYP1B1 expression partially
      overlapped with PPARgamma expression, which was also inversely related in clonal
      sub-lines. CYP1B1 expression may, therefore, represent an early stage of
      differentiation that requires factors associated with DNA synthesis to
      subsequently generate PPARgamma1.

PMID- 15967409
TI  - The tumor necrosis factor-alpha AU-rich element inhibits the stable association
      of the 40S ribosomal subunit with RNA transcripts.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine that is central to
      normal immune responses as well as autoimmune inflammatory diseases. The
      production of TNF-alpha protein is thus tightly regulated at multiple levels.
      Translational control is one of the means by which TNF-alpha production is
      repressed in unstimulated cells. To examine the mechanism by which the
      translation of TNF-alpha mRNA transcripts is repressed, we have used an in vitro
      translation system. The AU-rich element (ARE) in the 3' UTR of TNF-alpha
      transcripts was sufficient to confer translational repression. This effect was
      observed using transcripts containing a 5' m(7)G cap but not uncapped
      transcripts, and was independent of a poly(A) tail. Sucrose gradient analysis
      revealed that ARE-containing transcripts were present at relatively lower amounts
      in 80S-associated fractions and higher amounts in non-ribosome-bound RNA
      fractions, with no accumulation of 48S-associated transcripts. ARE-mediated
      translational repression was competitively inhibited by ARE-containing
      transcripts. These data indicate that a TNF-alpha ARE-binding trans-acting
      factor(s) inhibits the association of the 43S complex with RNA transcripts.

PMID- 15967410
TI  - Streptozotocin-induced diabetes in the rat is associated with enhanced tissue
      hydrogen sulfide biosynthesis.
AB  - This investigation is aimed to determine whether the biosynthesis of H(2)S, an
      endogenous vasodilator gas, is altered in the streptozotocin-diabetic rat. Plasma
      H(2)S concentration as well as the activity, and expression, of H(2)S
      synthesizing enzymes (namely cystathionine-gamma-lyase (CSE) and cystathionine
      beta-synthetase (CBS)) were measured in various tissues of non-diabetic,
      streptozotocin-diabetic and insulin-treated diabetic rats. H(2)S formation in
      pancreas and liver was increased in diabetic rats. Both CSE and CBS mRNAs were
      increased in liver of diabetic animals. Similarly, CBS mRNA was increased in
      pancreas. Insulin treatment restored the changes in H(2)S metabolism seen. The
      findings of this study suggest that the metabolism of H(2)S in pancreas and liver
      is altered in the streptozotocin-diabetic rat. This is the first study in which a
      derangement in H(2)S biosynthesis in diabetes has been demonstrated. H(2)S may
      play a part in the aetiology or development of diabetes in this animal model.

PMID- 15967411
TI  - A new beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) from Helicobacter
      pylori: Molecular cloning, enzymatic characterization, and structural modeling.
AB  - Helicobacter pylori is a gram-negative pathogenic bacterium that causes peptic
      ulcer disease and gastric cancer, and studies of the related potent enzymes
      associated with this bacterium are urgent for the discovery of novel drug
      targets. In bacteria, beta-hydroxyacyl-acyl carrier protein (ACP) dehydratase
      (FabZ) is a potent enzyme in fatty acid biosynthesis and catalyzes the
      dehydration of beta-hydroxyacyl-ACP to trans-2-acyl-ACP. In this study, the
      cloning and enzymatic characterization of FabZ from H. pylori strain SS1 (HpFabZ)
      were reported, and the gene sequence of HpfabZ was deposited in the GenBank
      database. Enzyme dynamic analysis showed that HpFabZ had a K(m) of 82.6+/-4.3
      microM toward its substrate analog crotonoyl-CoA. Dynamic light scattering and
      native-PAGE investigations suggested that HpFabZ exists as hexamer in native
      state. Enzymatic characterization and thermal-induced unfolding analysis based on
      circular dichroism spectral measurements indicated that HpFabZ is very stable
      against high temperature (90 degrees C). Such a high stability of HpFabZ was well
      elucidated by the strong H-bonds and hydrophobic interactions among the HpFabZ
      hexamer as investigated in the modeled HpFabZ hexamer structure. Our current
      study is hoped to provide useful information in better understanding the FabZ of
      H. pylori strain and further supply possible hints in the discovery of anti
      bacterial compounds using HpFabZ as target.

PMID- 15967412
TI  - Identification of N-arachidonylglycine, U18666A, and 4-androstene-3,17-dione as
      novel insulin Secretagogues.
AB  - The glucose-induced insulin secretion is fine-tuned by numerous factors. To
      systematically identify insulinotropic factors, we optimized a primary beta-cell
      based functional assay to monitor intracellular Ca2+ flux ([Ca2+]i). By this
      assay system, we successfully identified several insulinotropic peptides
      including cholecystokinin, gastrin releasing peptide, vasopressin, and oxytocin
      from tissue extracts. Screening of an assortment of chemical compounds, we
      determined three novel insulin secretagogues: N-arachidonylglycine (NAGly), 3beta
      (2-diethylamino-ethoxy) androstenone hydrochloride (U18666A), and 4-androstene
      3,17-dione. The NAGly increased [Ca2+]i through stimulation of the voltage
      dependent Ca2+ channels and it was dependent on extracellular glucose level. On
      the other hand, U18666A and 4-androstene-3,17-dione increased [Ca2+]i in the
      presence of K ATP channel opener diazoxide while it was inhibited by the presence
      of Ca2+ channel blocker nitrendipine, suggesting that their effects are
      independent of K ATP channel. These unique features will be useful for further
      development of insulinotropic factors and drugs for treating type 2 diabetes.

PMID- 15967413
TI  - Conserved autophosphorylation pattern in activation loops and juxtamembrane
      regions of Mycobacterium tuberculosis Ser/Thr protein kinases.
AB  - The identification of phosphorylation sites in proteins provides a powerful tool
      to study signal transduction pathways and to establish interaction networks
      involving signaling elements. Using different strategies to identify
      phosphorylated residues, we report here mass spectrometry studies of the entire
      intracellular regions of four 'receptor-like' protein kinases from Mycobacterium
      tuberculosis (PknB, PknD, PknE, and PknF), each consisting of an N-terminal
      kinase domain and a juxtamembrane region of varying length (26-100 residues). The
      enzymes were observed to incorporate different numbers of phosphates, from five
      in PknB up to 11 in PknD or PknE, and all detected sites were dephosphorylated by
      the cognate mycobacterial phosphatase PstP. Comparison of the phosphorylation
      patterns reveals two recurrent clusters of pThr/pSer residues, respectively, in
      their activation loops and juxtamembrane regions, which have a distinct effect on
      kinase activity. All studied kinases have at least two conserved phosphorylated
      residues in their activation loop and mutations of these residues in PknB
      significantly decreased the kinase activity, whereas deletion of the entire
      juxtamembrane regions in PknB and PknF had little effect on their activities.
      These results reinforce the hypothesis that mycobacterial kinase regulation
      includes a conserved activation loop mechanism, and suggest that phosphorylation
      sites in the juxtamembrane region might be involved in putative kinase-mediated
      signaling cascades.

PMID- 15967414
TI  - Differential expression of genes coding for EGF-like factors and ADAMTS1
      following gonadotropin stimulation in normal and transformed human granulosa
      cells.
AB  - We have demonstrated previously that the synthesis of epiregulin and
      amphiregulin, of the EGF-like growth factor family, is stimulated by luteinizing
      hormone in human follicular (granulosa) cells obtained from in vitro
      fertilization program. In the present work, we demonstrate that H89, a PKA
      inhibitor, attenuated the expression of these growth factors both in the mRNA and
      the protein levels, suggesting PKA involvement in this signaling pathway. SV40
      transformed human granulosa cells showed higher basal levels of epiregulin and
      amphiregulin than normal cells, which were still elevated following cAMP
      stimulation by Forskolin. Cleavage by a disintegrin and metalloproteinases
      (ADAMs) is essential for activation of these growth factors, allowing their
      interaction with EGF receptor. Expression of ADAMTS1 and ADAM12 was downregulated
      by cAMP in normal, but not in SV40-transformed cells, suggesting that in normal
      cells epiregulin and amphiregulin activity is downregulated by a feedback
      mechanism that may be lost in SV40-transformed cells and their loss of
      downregulation may be involved in the development of ovarian tumors.

PMID- 15967415
TI  - On the contentious sequence and glycosylation motif of the ribosome inactivating
      plant protein gelonin.
AB  - The amino acid sequence and the glycosylation motif of the ribosome inactivating
      protein (RIP) gelonin are identified by Fourier transform ion cyclotron resonance
      mass spectrometry. Intact gelonin as isolated from the seeds of Gelonium
      multiflorum consists of at least three different post-translational modified
      forms: analysis of gelonin peptides as obtained by proteolytic digestion is
      consistent with the amino acid sequence published by Nolan et al. High resolution
      mass determination established a glycosylation pattern of GlcNAc2Man(3-5)Xyl.
      N189 was identified as glycosylation site. The proposed glycan structure is
      consistent with a standard plant N-glycosylation pattern as found in other RIP.
      Based on these results we suggest that gelonin is located in the vacuole of
      Gelonium multiflorum seeds.

PMID- 15967416
TI  - Saururus cernuus lignans--potent small molecule inhibitors of hypoxia-inducible
      factor-1.
AB  - Hypoxia-inducible factor-1 (HIF-1) represents an important tumor-selective
      therapeutic target for solid tumors. In search of novel small molecule HIF-1
      inhibitors, 5400 natural product-rich extracts from plants, marine organisms, and
      microbes were examined for HIF-1 inhibitory activities using a cell-based
      reporter assay. Bioassay-guided fractionation and isolation, followed by
      structure elucidation, yielded three potent natural product-derived HIF-1
      inhibitors and two structurally related inactive compounds. In a T47D cell-based
      reporter assay, manassantin B1, manassantin A, and 4-O-methylsaucerneol inhibited
      hypoxia-induced HIF-1 activation with IC50 values of 3, 3, and 20 nM,
      respectively. All three compounds are relatively hypoxia-specific inhibitors of
      HIF-1 activation, in comparison to other stimuli. The hypoxic induction of HIF-1
      target genes CDKN1A, VEGF, and GLUT-1 were also inhibited. These compounds
      inhibit HIF-1 by blocking hypoxia-induced nuclear HIF-1alpha protein accumulation
      without affecting HIF-1alpha mRNA levels. In addition, preliminary structure
      activity studies suggest specific structural requirements for this class of HIF-1
      inhibitors.

PMID- 15967418
TI  - Long-lasting rewarding effects of morphine induced by drug primings.
AB  - To evaluate the persistence of the rewarding effects of morphine, the
      acquisition, maintenance, extinction and reinstatement of a conditioned place
      preference (CPP) was assessed in OF1 mice. In Experiment 1, the persistence of
      morphine-induced CPP was evaluated weekly. Mice showed CPP after four sessions of
      conditioning with 5, 10, 20 and 40 mg/kg of morphine, which lasted 0, 1, 2 and 4
      weeks, respectively. In Experiment 2, after four sessions of conditioning with 40
      mg/kg of morphine, the effects of four schedules of extinction differing in the
      time interval (2, 4, 6 or 8 weeks) between sessions were evaluated. CPP was no
      longer evident after 8 weeks for the groups examined each 2 or 8 weeks and after
      12 weeks for the groups examined each 4 and 6 weeks. After extinction, the
      reinstating effects of a priming dose of 20 mg/kg of morphine were demonstrated.
      This procedure of extinction/reinstatement was repeated with a decreasing priming
      dose of morphine (10, 5, 2.5 and 1.25 mg/kg) until a noneffective dose was found.
      These results show that morphine-induced CPP is very persistent over time,
      suggesting that drug exposure induces long-lasting changes in the brain, which
      supports the idea that drug addiction must be considered as a chronic, lifelong
      disorder.

PMID- 15967417
TI  - Oxytocin increases the density of high affinity alpha(2)-adrenoceptors within the
      hypothalamus, the amygdala and the nucleus of the solitary tract in
      ovariectomized rats.
AB  - Oxytocin induces long-term changes in, for example, blood pressure, spontaneous
      motor activity and corticosterone levels in rats. Previous studies in male rats
      have suggested a role for alpha(2)-adrenoceptors within the central nervous
      system in these effects. The aim of the present study was to investigate if
      oxytocin treatment in female rats would influence alpha(2)-adrenoceptors within
      the hypothalamus, the amygdala and the nucleus of the solitary tract (NTS). For
      this purpose, female ovariectomized (OVX) rats were treated with oxytocin (1
      mg/kg s.c.) or saline once a day for 10 days. Rats were decapitated 5 days after
      the last injection, and brains and plasma were collected. Quantitative receptor
      autoradiography for characterization of high affinity alpha(2)-adrenoceptor
      agonist binding and radioimmunoassay for corticosterone were performed. Oxytocin
      increased the B(max) values of the alpha(2)-adrenoceptor agonist [3H]UK14.304
      binding sites significantly in all the analyzed areas (P<0.05). K(d) values were
      unchanged. Plasma levels of corticosterone were significantly decreased in the
      oxytocin-treated rats (P<0.05). These findings are in further support of an
      interaction between oxytocin receptors and alpha(2)-adrenoceptors and show that
      oxytocin treatment may increase alpha(2)-adrenoceptor recognition probably
      leading to an increase in alpha(2)-adrenoceptor signaling in several parts of the
      brain.

PMID- 15967419
TI  - Chronic sucrose ingestion enhances mu-opioid discriminative stimulus effects.
AB  - Sucrose affects a variety of opioid-related behaviors. We hypothesized that, if
      sucrose ingestion alters opioidergic circuitry, opioid-induced discriminative
      stimulus effects would be enhanced following sucrose intake. In the present
      study, rats were trained to discriminate nalbuphine (3.2 mg/kg, s.c.) from saline
      in an operant choice procedure. After acquiring the discrimination, subjects were
      injected with a single nalbuphine dose (0.1-3.2 mg/kg) and given 30-min access to
      30% sucrose or water. Sucrose consumption did not alter nalbuphine's
      discriminative stimulus effects under these conditions. During subsequent tests,
      training was suspended, and rats received continuous access to sucrose (9 days)
      or water (8 days). Chronic sucrose consumption increased the potency of
      nalbuphine to produce its discriminative stimulus effects by 3-fold. These
      findings suggest chronic sucrose consumption results in changes in opioid-system
      function that modulates the effects of exogenously administered opioids.

PMID- 15967420
TI  - Reduced cardiac hypertrophy in toll-like receptor 4-deficient mice following
      pressure overload.
AB  - OBJECTIVE: We have previously demonstrated that nuclear factor kappa B (NFkappaB)
      activation is needed for the development of cardiac hypertrophy in vivo. NFkappaB
      is a downstream transcription factor in the Toll-like receptor (TLR)-mediated
      signaling pathway; therefore, we investigated a role of TLR4 in cardiac
      hypertrophy in vivo. METHODS: TLR4-deficient mice (C.C3H-Tlr4(lps-d), n = 6),
      wild-type (WT) genetic background mice (BALB/c, n = 6), TLR4-deleted strain
      (C57BL/10ScCr, n = 8), and WT controls (C57BL/10ScSn, n = 8) were subjected to
      aortic banding for 2 weeks. Age-matched surgically operated mice served as
      controls. In a separate experiment, rapamycin (2 mg/kg, daily) was administered
      to TLR4-deficient mice and WT mice immediately following aortic banding. The
      ratio of heart weight/body weight (HW/BW) was calculated, and cardiac myocyte
      size was examined by FITC-labeled wheat germ agglutinin staining of membranes.
      NFkappaB binding activity and the levels of phospho-p70S6K in the myocardium were
      also examined. RESULTS: Aortic banding significantly increased the ratio of HW/BW
      by 33.9% (0.601 +/- 0.026 vs. 0.449 +/- 0.004) and cell size by 68.4% in WT mice
      and by 10.00% (0.543 +/- 0.011 vs. 0.495 +/- 0.005) and by 11.8% in TLR4
      deficient mice, respectively, compared with respective sham controls. NFkappaB
      binding activity and phospho-p70S6K levels were increased by 182.6% and 115.2% in
      aortic-banded WT mice and by 78.0% and 162.0% in aortic-banded TLR4-deficient
      mice compared with respective sham controls. In rapamycin-treated aortic-banded
      mice, the ratio of HW/BW was increased by 18.0% in WT mice and by 3.5% in TLR4
      deficient mice compared with respective sham controls. CONCLUSION: Our results
      demonstrate that TLR4 is a novel receptor contributing to the development of
      cardiac hypertrophy in vivo and that both the TLR4-mediated pathway and
      PI3K/Akt/mTOR signaling are involved in the development of cardiac hypertrophy in
      vivo.

PMID- 15967421
TI  - Role of SHP-1, Kv.1.2, and cGMP in nitric oxide-induced ERK1/2 MAP kinase
      dephosphorylation in rat vascular smooth muscle cells.
AB  - OBJECTIVE: Nitric oxide (NO) elicits relaxation in vascular smooth muscle cells
      (VSMC) that is associated with guanylate cyclase (GC) and K(+) channel
      activation. In this study we determined the mechanisms that lead to ERK1/2 MAP
      kinase dephosphorylation in response to NO. METHODS: VSMC were treated with the
      NO donor SNAP or sodium nitroprusside (SNP), and ERK1/2, Src homology (SH) 1
      domain-containing protein tyrosine phosphatase (SHP-1), and Kv.1.2
      phosphorylation were assessed by immunoprecipitation and Western blot analysis.
      RESULTS: NO decreased basal ERK1/2 phosphorylation in a dose- and time-dependent
      manner. NO-induced ERK1/2 dephosphorylation was detected at 1 min and sustained
      for 30 min. Pre-treatment with the GC inhibitor ODQ or the protein tyrosine
      phosphatase inhibitor I prevented ERK1/2 dephosphorylation induced by SNAP. The
      inhibition of protein phosphatase 1A/2A had no effect on ERK1/2 dephosphorylation
      induced by SNAP. Treatment with cromakalim A, a nonspecific K(+) channel
      activator, also induced ERK1/2 dephosphorylation, while blockade of Kv.1.2 K(+)
      channels (AM92016 hydrochloride) prevented NO-induced ERK1/2 dephosphorylation.
      In addition, SNAP induced SHP-1 phosphorylation, and the Kv.1.2 dephosphorylation
      increase and SHP-1 phosphorylation was blocked by ODQ or AM92016. The basal
      interaction between ERK1/2 and SHP-1 was decreased in response to SNAP
      stimulation. SHP-1 also interacted with Kv.1.2 under basal conditions and
      participates in Kv.1.2 activation. Using the mouse mesenteric resistance artery,
      we found that ERK1/2 MAP kinase is involved in regulation of myogenic tone.
      CONCLUSION: Thus, our study provides the first evidence that NO controls basal
      ERK1/2 phosphorylation by a signaling cascade that involves a dynamic signaling
      complex between cGMP, Kv.1.2 and SHP-1.

PMID- 15967422
TI  - Trichosanthin inhibits antigen-specific T cell expansion through nitric oxide
      mediated apoptosis pathway.
AB  - Trichosanthin (TCS) has been found to exhibit inflammation-suppressing effect but
      the underlying mechanisms are not clear. In this study, we found that TCS
      inhibited OVA-specific T cell proliferation in a dose-dependent manner. Such
      inhibition was correlated with enhanced cell death. At the same time, inducible
      nitric oxide synthase (iNOS) mRNA expression and protein levels were found
      increased in cells treated with TCS, and nitric oxide (NO) production by cells
      was elevated in the presence of TCS. When L-NIL, the specific inhibitor of iNOS,
      was added to suppress NO production induced by TCS, OVA-specific cell death was
      significantly inhibited, meanwhile, thymidine incorporation of cells was rescued
      towards normal levels. These results indicate that TCS could inhibit antigen
      specific T cell activation via NO-mediated apoptosis pathway.

PMID- 15967423
TI  - Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome.
AB  - Contradictory reports have suggested that serum free carnitine and acylcarnitine
      concentrations are decreased in patients with chronic fatigue syndrome (CFS) and
      that this is a cause of the muscle fatigue observed in these patients. Others
      have shown normal serum free carnitine and acylcarnitines in similar patients. We
      report here studies on free, total and esterified (acyl) carnitines in urine and
      blood plasma from UK patients with CFS and three control groups. Plasma and timed
      urine samples were obtained from 31 patients with CFS, 31 healthy controls, 15
      patients with depression and 22 patients with rheumatoid arthritis. Samples were
      analysed using an established radioenzymatic procedure for total, free and
      esterified (acyl) carnitine. There were no significant differences in plasma or
      urinary total, free or esterified (acyl) carnitine between UK patients with CFS
      and the control groups or in renal excretion rates of these compounds. The data
      presented here show that, in the CFS patients studied, there are no significant
      abnormalities of free or esterified (acyl) carnitine. It is thus unlikely that
      abnormalities in carnitine homeostasis have any significant role in the aetiology
      of their chronic fatigue.

PMID- 15967424
TI  - A roof plate-dependent enhancer controls the expression of Homeodomain only
      protein in the developing cerebral cortex.
AB  - The smallest known homeodomain protein, Homeodomain only protein (Hop), was
      identified and described here as a temporally and spatially restricted gene in
      the neurogenic regions of the developing murine CNS including the cerebral
      cortex. Furthermore, an evolutionarily conserved 418 base pair upstream cis
      regulatory DNA sequence was found to confine the Hop expression to the CNS of
      transgenic mice, but not to the heart which is the second major Hop expressing
      organ Chen, F., Kook, H., Milewski, R., Gitler, A.D., Lu, M.M., Li, J., Nazarian,
      R., Schnepp, R., Jen, K., Biben, C., Runke, G., Mackay, J.P., Novotny, J.,
      Schwartz, R.J., Harvey, R.P., Mullins, M.C., Epstein, J.A., 2002. Hop is an
      unusual homeobox gene that modulates cardiac development. Cell 110, 713-723;
      Shin, C.H., Liu, Z.P., Passier, R., Zhang, C.L., Wang, D.Z., Harris, T.M.,
      Yamagishi, H., Richardson, J.A., Childs, G., Olson, E.N., 2002. Modulation of
      cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110,
      725-735. The forebrain enhancer activity was successfully reproduced in vitro
      utilizing a combination of the electroporation and the organotypic brain culture
      method. Using this approach, the minimal requirement for the forebrain-specific
      enhancer sequence was delineated down to 200 base pairs. We further demonstrate
      that the Hop enhancer activity is inducible ectopically in a transgenic tissue by
      wild-type roof plate transplantation in vitro. Thus Hop is regulated in the
      forebrain by a so far unidentified paracrine signaling factor from the roof
      plate. Furthermore, the identified enhancer sequence provides an important tool
      for the targeted expression of transgenes in the medial cortex and the cortical
      hem.

PMID- 15967425
TI  - Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate is a
      novel positive modulator of GABAA receptors.
AB  - Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41)
      enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam
      to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus
      oocytes expressing various recombinant GABA(A) receptor subtypes revealed that
      TG41 enhanced the function of all receptor subunit combinations tested. The
      potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was
      greater than that of alphaxalone, etomidate, propofol, or pentobarbital. The
      potency of TG41 was also greater at receptors containing alpha1 or alpha2
      subunits than at those containing alpha4 and it was markedly higher at receptors
      containing beta2 or beta3 subunits than at those containing beta1. This drug
      induced a reversible loss of the righting reflex in Xenopus tadpoles and it
      elicited hypnosis (5 mg/kg) after intravenous administration in rats. These
      results indicate that the pharmacological profile of TG41 is similar to that of
      general anesthetics which potentiate the activity of GABA(A) receptors containing
      the beta2 or beta3 subunit.

PMID- 15967426
TI  - Relationship between vasodilation capacity and phenolic content of Spanish wines.
AB  - We aimed to determine: 1) the concentration of polyphenols in Spanish red wines,
      2) the vasodilatory properties of those wines in relation with their polyphenol
      concentrations and 3) the vasodilation induced by some of these polyphenols in
      rat aortic rings. In the wines studied the concentration of rutin and kaempferol
      was high compared with other polyphenols. All wines relaxed precontracted rat
      aortic rings and this effect was directly related with the concentration of
      myricetin and kaempferol in the wines. Kaempferol and rutin also induced
      endothelium-dependent and independent relaxation, kaempferol was more potent.
      This relaxation was not inhibited by the estrogen receptor alpha antagonist ICI
      182,760. Kaempferol also potentiated the endothelium-dependent relaxation induced
      by acetylcholine, which was reversed by Nw-nitro-l-arginine methyl ester (l
      NAME). These findings show a good correlation between the concentration of
      polyphenols (especially kaempferol) of Spanish red wines and the vasodilatory
      effect, which may confer on them unique features in the prevention of
      cardiovascular disease.

PMID- 15967427
TI  - Pre-junctional effects of oximes on [3H]-acetylcholine release in rat hippocampal
      slices during soman intoxication.
AB  - In this study, the non-reactivating effects of oximes in the hippocampus of the
      rat are investigated. The potassium (51 mM) evoked release of [(3)H]
      acetylcholine and the liberation of [(3)H]-choline were determined in hippocampal
      slices following in vitro exposure to soman and five oximes (toxogonin, HI-6, HLo
      7, P2S and 2-PAM) in separate experiments by superfusion. In the absence of
      soman, toxogonin and HLo-7 in particular induced a concentration dependent
      significant increase in the evoked release of [(3)H]-acetylcholine. There was
      also a significant effect of HI-6, but the effect was much smaller. Two
      pralidoxime salts, P2S (methanesulfonate salt) and 2-PAM (methiodide salt), had
      similar but lower effects that were only observed at relatively high
      concentrations. Experiments performed following complete inhibition of the
      acetylcholinesterase activity by soman (1.0 microM) showed that HI-6 and HLo-7
      induced a significant decrease in the potassium-evoked release of [(3)H]
      acetylcholine, while the liberation of [(3)H]-choline increased. Toxogonin, P2S
      and 2-PAM did not reduce significantly the evoked release of [(3)H]
      acetylcholine. Only limited reactivation of the acetylcholinesterase activity was
      observed in superfusion experiments with toxogonin, HI-6, P2S and 2-PAM following
      exposure of hippocampal slices to soman. However, HLo-7 was proved to be
      relatively more effective in reactivating the acetylcholinesterase activity at
      high concentrations (50 and 200 microM). The acetylcholinesterase activity was
      reactivated to approximately 12% and 40% of control, respectively. It is
      concluded that HI-6 and HLo-7 have important non-acetylcholinesterase
      reactivating properties following soman poisoning, as may be seen by the
      significant reduction in the evoked release of [(3)H]-acetylcholine effected by
      these oximes. HLo-7 is of particular interest in view of its ability to
      additionally improve reactivation of the acetylcholinesterase activity.

PMID- 15967428
TI  - Intravenous butyrylcholinesterase administration and plasma and brain levels of
      cocaine and metabolites in rats.
AB  - Butyrylcholinesterase is a major cocaine-metabolizing enzyme in humans and other
      primates, catalyzing hydrolysis to ecgonine methylester. Increasing
      butyrylcholinesterase activity may be a treatment for cocaine addiction. We
      evaluated the effect of 30-min pretreatment with horse-derived
      butyrylcholinesterase (5-15,000 U i.v.) or with the selective
      butyrylcholinesterase inhibitor cymserine (10 mg/kg i.v.) on the metabolism of
      cocaine (17 mg/kg i.p.) in anesthetized rats. Venous blood samples were collected
      for two hours after cocaine administration and later assayed for cocaine and
      metabolites by gas chromatography/mass spectroscopy. Whole brains were collected
      after the last blood sample and similarly assayed. Butyrylcholinesterase
      significantly increased plasma and brain ecgonine methylester levels and
      decreased cocaine plasma half-life from 26.2 min (saline) to 16.4 min (15,000 U).
      Butyrylcholinesterase had no significant effect on plasma or brain cocaine or
      benzoylecgonine levels. Cymserine had no effect on any variable. These findings
      suggest that butyrylcholinesterase treatment may have benefits in enhancing
      cocaine metabolism and in increasing levels of ecgonine methylester, which may
      have a protective action against cocaine.

PMID- 15967429
TI  - Effects of acute olanzapine after sustained fluoxetine on extracellular monoamine
      levels in the rat medial prefrontal cortex.
AB  - The combination of selective serotonin reuptake inhibitors with atypical
      antipsychotic drugs exhibits beneficial effects in treatment-resistant
      depression. We investigated the effects of a 2-week treatment with a low
      fluoxetine dose (3 mg/kg per day) plus a single injection of olanzapine (3 mg/kg)
      on the dialysate concentration of noradrenaline, dopamine and serotonin (5-HT) in
      the medial prefrontal cortex of the rat. Chronic fluoxetine increased only 5-HT
      levels whereas single olanzapine administration increased the concentration of
      catecholamines and decreased that of 5-HT to a comparable extent in vehicle- and
      fluoxetine-treated rats. Therefore, it is possible that the therapeutic benefit
      of this pharmacological combination may not be associated to changes in the
      cortical concentration of monoamines, but to postsynaptic blockade of
      monoaminergic receptors.

PMID- 15967431
TI  - Interaction of lens alpha and gamma crystallins during aging of the bovine lens.
AB  - Heterologous, noncovalent interactions of lens crystallins, such as between alpha
      and gamma crystallin, are thought to play a key role in the transparent
      properties of the lens. To determine possible interactions between these two
      types of crystallins, bovine gamma B crystallin in its native state was purified
      from whole fetal lenses or from the nucleus of aged bovine lenses, and the
      purified protein was passed over immobilized alpha crystallin, using a surface
      plasmon resonance instrument (BIAcore 3000) to obtain refractive units (RU) of
      gamma B binding at equilibrium. The results demonstrate low binding of gamma B
      crystallin purified from fetal lenses, but higher binding of the same gamma
      species purified from aged lenses. Together, these results demonstrate that under
      equilibrium conditions, gamma B crystallin from the aging bovine lens shows
      increased noncovalent associations with alpha crystallins, consistent with the
      possibility that such interactions play an important role in the transparent
      properties of the aged lens.

PMID- 15967430
TI  - Serca isoform expression in the mammalian retina.
AB  - The sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) is a key
      intracellular calcium transporter, which regulates cellular calcium concentration
      [Ca2+] by transporting Ca2+ ions from the cytosol into the endoplasmic reticulum.
      SERCA-mediated Ca2+ sequestration controls proper folding of newly synthesized
      proteins within the ER as well as the timing and spatial patterning of
      depolarization-evoked Ca2+ responses in the cytoplasm. To understand the spatial
      and temporal properties of Ca2+ homeostasis in retinal neurons better, I studied
      expression and distribution of all three SERCA isoforms in the mouse retina using
      isoform-specific antibodies. No immunostaining was observed with the SERCA1
      antibody. SERCA2 was expressed in photoreceptor inner segments, amacrine and
      ganglion cells of the mouse retina. Similar SERCA2 localization was observed in
      adult rat, macaque and ground squirrel retinas. Analysis of distribution of
      SERCA2 immunofluorescence in the developing mouse retina revealed prominent
      SERCA2 signals throughout postnatal development. The N89 antibodys used to
      identify the SERCA3 isoforms labelled cone outer segments, inner segments of
      photoreceptors and cell processes in the inner nuclear layer of the mouse retina.
      These results imply that the SERCA2 isoform controls Ca2+ sequestration into the
      endoplasmic reticulum in most classes of retinal neuron. A potential role for
      SERCA3 in cone function is suggested.

PMID- 15967432
TI  - Incomplete replacement of docosahexaenoic acid by n-6 docosapentaenoic acid in
      the rat retina after an n-3 fatty acid deficient diet.
AB  - When sources of n-3 fatty acids are not present in the diet, nervous system
      docosahexaenoic acid (22:6n3) is replaced by docosapentaenoic acid (22:5n6). Dams
      were fed either an n-3 deficient diet or one containing alpha-linolenic acid
      (18:3n3) and 22:6n3 throughout pregnancy and lactation. Their male offspring at
      weaning also received either the n-3 deficient or n-3 adequate diets and were
      sacrificed at 5, 10, 20, 50 and 91 days of age. Retinal lipids were extracted and
      analysed by gas chromatography for fatty acyl content. The percentage of retinal
      22:6n3 increased continuously over the 13 week course of the experiment but
      reached its maximal concentration around day 20. Non-reciprocal replacement of
      22:6n3 by 22:5n6 was observed at postnatal day 20 and 50 but not at other time
      points. Complete replacement of 22:6n3 was apparent if elevations in both 22:5n6
      and docosatetraenoic acid (22:4n6) were considered. These data indicate that
      during the rapid period of accretion of retinal 22:6n3 around postnatal day 20,
      the supply of 22:5n6 to the retina was inadequate to completely replace 22:6n3 in
      n-3 deficient rats.

PMID- 15967433
TI  - Age, gender and region-specific differences in drug metabolising enzymes in rat
      ocular tissues.
AB  - Previously we have reported our analyses of cytochrome P450 (CYP) expression in
      rat ocular tissues and in our current study we have extended these analyses to
      the different stages of growth in both male and female rats. Additionally, we
      have examined the expression levels of the different conjugation enzymes,
      sulfotransferases (SULTs), UDP-glucuronosyl transferases (UGTs) and glutathione S
      transferases (GSTs), in ocular tissues. In 5-week-old animals, the CYP genes,
      CYP2B2 and CYP3A1, were abundantly expressed in the lens, with higher CYP1A1
      expression detectable in the extra-lenticular tissues, of both genders. However,
      the expression of CYP1A2 and CYP2E1 in female ocular tissues was more extensive
      than in male. Moreover, in females the expression of the phenol-sulfating SULTs,
      ST1A1, ST1B1 and ST1C1, was more abundant in the extra-lenticular tissues,
      whereas the levels of the hydroxysteroid-sulfating SULTs, ST2A1 and ST2A5,
      predominated in the lens. The expression levels of the UGTs, UGT1A1, UGT1A6 and
      UGT2B1, were also higher in the female extra-lenticular tissues but the
      expression of the GSTA subfamily (GSTA1 and GSTA2) was very weak in the ocular
      tissues of both genders. The overall gene expression profiles were found to
      change with the age of the animals (from 3 to 8 weeks) and, in general, the
      expression levels of the CYPs and SULTs declined with age, whereas the levels of
      the UGTs and GSTs increased. These results demonstrate that the expression
      profiles of drug metabolising enzymes show both region- and gender-specific
      patterns in rat ocular tissues.

PMID- 15967434
TI  - Heterogeneous populations of microglia/macrophages in the retina and their
      activation after retinal ischemia and reperfusion injury.
AB  - Activation of Microglia/macrophages has been observed in ischemia-reperfusion
      injury of the brain. This study was undertaken to investigate the different
      subpopulations of microglia/macrophages in the normal rat retina and their
      activation after retinal ischemia. Retinal ischemia was induced by elevation of
      intraocular pressure to 120 mmHg for 60 min. Microglia/macrophages were
      identified on frozen retinal sections by four antibodies, namely OX42, 5D4, OX6
      and ED1. In the normal retina, there were heterogeneous populations of resident
      microglia/macrophages as characterized by their differences in morphology,
      antigen expression and distribution. OX42+ cells had delicate processes and were
      located in the inner layers of the retina, while 5D4+ cells were highly ramified
      and mostly scattered in the inner plexiform layer (IPL) and the outer plexiform
      layer. Few amoeboid ED1+ cells were also seen in the ganglion cell layer and IPL.
      OX6+ (MHC-II antigen presenting) cells were not detected in the normal retinas.
      Double labeling with OX42 and 5D4 antibodies on normal retinal sections showed
      few microglia exhibited positive labeling with both OX42 and 5D4, while the
      majority of the microglia were labeled with either OX42 or 5D4 antibodies. After
      retinal ischemia single labeling with these antibodies showed increased number of
      these antigen-expressing cells, disappearance of normal cellular processes, and
      rounding or amoeboid like appearance of the cell bodies. At 1 day after ischemia,
      there was a significant infiltration of round OX42+, ED1+ and OX6+ cells with
      loss of the cellular processes in the inner retina. From 3 to 14 days, all
      subpopulations of microglia/macrophages differentiated cellular processes and
      became dendritic again. Double labeling on retinas after 1 day of recovery showed
      OX42+ cells were co-labeled with ED1+ or OX6+ cells, but not with 5D4+ cells.
      Scattered amoeboid OX42+, 5D4+, and ED1+ cells were noted in the subretinal space
      3-14 days after ischemia. In summary, there were heterogeneous populations of
      resident microglia/macrophages in the normal inner retina and they were activated
      early after ischemia-reperfusion injury and exhibited different antigenic
      expression which were further altered in the recovery phase.

PMID- 15967435
TI  - Suppression of choroidal neovascularization by intramuscular polymer-based gene
      delivery of vasostatin.
AB  - The purpose of this study was to evaluate the efficacy of gene delivery of
      angiogenesis inhibitor, vasostatin (VS), in suppressing experimental model of
      choroidal neovascularization (CNV). A mammalian expression vector carrying VS,
      pCMV3-VS, was constructed and evaluated for its ability to produce VS in
      transfected cells using western blot analysis and a cell viability assay. CNV was
      induced in Brown Norway rats by fundus argon laser photocoagulation and evaluated
      by fundus fluorescein angiography (FAG). Ten days post-laser treatment, gene
      delivery was achieved by intramuscular (IM) injection of poly-(N-vinyl
      pyrrolidone) (PVP) polymer conjugated with pCMV3-VS (PVP-VS) or a control vector
      (PVP-vector). Systemic VS expression was analysed by western blot analysis and
      enzyme linked immunosorbent assay (ELISA), and the extent of CNV was monitored by
      FAG analysis at different time intervals post-PVP treatment. Transfection of
      pCMV3-VS into muscle cells resulted in increased production and release of
      exogenous VS, which specifically inhibited the proliferation of endothelial
      cells. Besides, IM injection of PVP-VS, but not PVP-vector, led to elevated VS
      level in plasma for 30 days. After laser photocoagulation, rats injected with PVP
      VS exhibited significantly lower incidence of CNV comparing with animals of
      control groups (P < 0.01) for at least 42 days. Moreover, rats treated with PVP
      VS also showed a significant reduction in the CNV lesions compared with control
      groups (P < 0.001) for at least 42 days. Above all, no overt adverse effects were
      observed in rats received PVP-VS. These results demonstrate the potential of IM
      VS gene delivery for CNV treatment.

PMID- 15967436
TI  - Regulation of lens aldose reductase activity by nitric oxide.
AB  - To examine the regulation of aldose reductase (AR) activity by nitric oxide (NO)
      in human lens epithelial cells (HLEC), cultured rat lens, and normal and diabetic
      rat lens, we have incubated HLEC or cultured rat lenses with 1 mm of the NO
      donors S-nitroso-N-acetylpenicillamine (SNAP) or S-nitrosoglutathione (GSNO), and
      the AR activity and sorbitol content were measured. Non-diabetic and diabetic
      (treated with streptozotocin 65 mg kg(-1) body wt, i.p.) rats were injected with
      the nitric oxide synthase (NOS) inhibitor, L-NAME (50 mg kg(-1) body wt day(-1),
      x 10 days i.p.) or NOS substrate, L-arginine (200 mg kg(-1) body wt day(-1), x 10
      days i.p.). In a separate group of rats, a nitroglycerin (NG)-patch that releases
      200 ng min(-1) NO was applied to the dorsal neck region. After 10 days of
      treatment, the lenses were removed and their AR activity and sorbitol content
      were measured. Incubation of HLEC with SNAP or GSNO reduced AR activity. A
      similar reduction in AR activity and sorbitol accumulation was observed when
      diabetic and non-diabetic rat lenses were cultured in the presence of SNAP and
      GSNO. Total protein-SSG in diabetic lens was lower compared to normal lens.
      Treatment of diabetic and non-diabetic rats with L-NAME enhanced AR activity and
      sorbitol accumulation, whereas NG patch and L-arginine significantly decreased AR
      activity and sorbitol accumulation in diabetic lenses compared to non-diabetic.
      Increased S-glutathiolation of AR was observed in the presence of SNAP. These
      results suggest that decreased glutathiolation of cellular proteins in diabetic
      rat lens compared to non-diabetic lens is related to decreased NO availability in
      diabetic rats which would decrease GSNO. Restoring the NO levels in diabetic
      animals increases glutathiolation of cellular proteins, inhibits AR activity and
      prevents sorbitol accumulation. Exogenous delivery of NO may represent a
      potentially useful strategy for preventing or delaying diabetic cataractogenesis
      and the development of other diabetic complications.

PMID- 15967437
TI  - alpha-Crystallin binding in vitro to lipids from clear human lenses.
AB  - The association of alpha-crystallin to lens membranes increases with age and
      cataract. Lipid compositional changes also occur with age, cataract, and
      diabetes. In this study we determined the influence of lipid compositional
      differences on the binding capacity of alpha-crystallin to lipid vesicles in
      vitro. Lipids were extracted from pools of human lenses from younger (22+/-4 y,
      n=30) and older (69+/-3 y, n=26) nondiabetic donors as well as from diabetics
      taking insulin (60+/-9 y, n=26) and diabetics not taking insulin (58+/-9 y,
      n=20). Diabetics were insulin dependent for an average of 6 years. Extracted
      lipids were extruded into large unilamellar vesicles. alpha-Crystallin was mixed
      with the lipid at 36 degrees C, allowed to bind for about 12 h, and centrifuged
      at 14,000 g. This centrifugal force was low enough to not pellet free alpha
      crystallin but high enough to pellet the lipid and bound alpha-crystallin. alpha
      Crystallin-lipid binding was characterized by comparing the amount alpha
      crystallin in the pellets of samples with and without lipid. Protein was measured
      using an assay that minimized interference from lipids. Lipid composition was
      determined by 31P-NMR spectroscopy. The binding capacity of alpha-crystallin to
      lipids was 12, 19, 8.9, 17 microg bound/mg lipid for lens lipids extracted from
      younger, older, insulin-treated and nontreated diabetic donors, respectively. The
      amount of alpha-crystallin in the pellet (bound alpha-crystallin) was
      significantly lower for the lipids from the younger group of lenses, p=0.033 and
      insulin-treated group, p=0.006, compared with the older group of lenses. Higher
      binding capacity was associated with a higher relative amount of sphingolipid and
      lower relative amounts of phosphatidylethanolamine-related lipid and
      phosphatidylcholine. The binding capacity of alpha-crystallin to lens lipids,
      measured in vitro, increases with age and decreases in diabetic donors that were
      treated with insulin. Our data support the idea that with age and perhaps certain
      types of diabetes, more alpha-crystallin is bound to the membrane and serves as a
      condensation point to which other crystallins bind and then become oxidized.

PMID- 15967438
TI  - Toxicity of oxidized beta-carotene to cultured human cells.
AB  - Carotenoids are effective antioxidants in vitro, but they are also susceptible to
      autoxidation, which generates volatile and biologically active aldehydes and
      ketones. In a previous study, we showed that autoxidized beta-carotene inhibits
      Na+-K+-ATPase activity more effectively than aldehydic products derived from
      lipid peroxidation, such as 4-hydroxynonenal. In this study, we compared
      mitochondrial dysfunction in cultured human K562 erythroleukaemic and 28 SV4
      retinal pigment epithelium (RPE) cells in response to the degradation products of
      beta-carotene autoxidation using the MTT assay. We found that oxidized beta
      carotene is cytotoxic and that mitochondrial function is decreased in both K562
      and RPE cells. In addition, the RPE cells were more resistant to this form of
      oxidative stress, suggesting that its cytotoxicity may depend on cellular
      antioxidant capacity.

PMID- 15967439
TI  - Intravenous infusion of immortalized human mesenchymal stem cells protects
      against injury in a cerebral ischemia model in adult rat.
AB  - Intravenous infusion of bone marrow cells has demonstrated therapeutic efficacy
      in animal models of cerebral ischemia and spinal cord injury. We intravenously
      delivered human mesenchymal stem cells (SH2+, SH3+, CD34-, and CD45-)
      immortalized with a human-telomerase gene (hTERT-MSCs) and transfected with eGFP
      or LacZ into rats 12 h after induction of transient middle cerebral artery
      occlusion (MCAO), to study their potential therapeutic benefit. hTERT-MSCs were
      delivered at 12 h after lesion induction. Lesion size was assessed using MR
      imaging and spectroscopy, and histological methods. Functional outcome was
      assessed using the Morris water maze and a treadmill test. Intravenous delivery
      of hTERT-MSCs reduced lesion volume and the magnitude of the reduction and
      functional improvement was positively correlated with the number of cells
      injected. The reduction of lesion size could be assessed in vivo with MRI and MRS
      and was correlated with subsequent histological examination of the brain. This
      work demonstrates that highly purified hTERT-MSCs reduce cerebral infarction
      volume and improve functional outcome.

PMID- 15967440
TI  - DNA-binding proteins of the Whirly family in Arabidopsis thaliana are targeted to
      the organelles.
AB  - Arabidopsis thaliana contains three genes with high homology to potato p24 which
      was described as a member of the Whirly family of nuclear transcriptional
      activators. Computer-based analysis revealed that all Arabidopsis Whirly (Why)
      proteins contain targeting sequences for either plastids or mitochondria. The
      functionality of these sequences was demonstrated by in vitro import assays into
      isolated organelles. Transient expression of GFP fusion proteins in protoplasts
      and onion epidermal cells confirmed the localisation of these proteins in
      plastids or mitochondria, respectively. The possession of organellar targeting
      sequences seems to be conserved among Why proteins of higher plant species,
      including potato p24.

PMID- 15967441
TI  - Facilitated release of substrate protein from prefoldin by chaperonin.
AB  - Prefoldin is a chaperone that captures a protein-folding intermediate and
      transfers it to the group II chaperonin for correct folding. However, kinetics of
      interactions between prefoldin and substrate proteins have not been investigated.
      In this study, dissociation constants and dissociation rate constants of unfolded
      proteins with prefoldin were firstly measured using fluorescence microscopy. Our
      results suggest that binding and release of prefoldin from hyperthermophilic
      archaea with substrate proteins were in a dynamic equilibrium. Interestingly, the
      release of substrate proteins from prefoldin was facilitated when chaperonin was
      present, supporting a handoff mechanism of substrate proteins from prefoldin to
      the chaperonin.

PMID- 15967442
TI  - Expression and functional characterization of LRRC4, a novel brain-specific
      member of the LRR superfamily.
AB  - LRRC4, a novel member of LRR superfamily thought to be involved in development
      and tumorigenesis of the nervous tissue, has the potential to suppress
      tumorigenesis and cell proliferation of U251MG cells. This study aimed at
      revealing the correlation between expression of LRRC4 and the maintenance of
      normal function and tumorigenesis suppression within the central nervous system.
      We systematically analyzed the expression and tissue distributions of the gene in
      tissues. Results showed that LRRC4 expression was limited to normal adult brain,
      both in human and in mouse, and exhibited a development-regulated pattern, but
      was down-regulated in brain tumor tissues and U251MG cell line. Furthermore,
      dynamic alterations in gene expression associated with cell cycle progression
      were investigated by using Tet-on system. Results showed that LRRC4 induced a
      cell cycle delay at the late G1 phase, probably through the alteration of the
      expression of different cell cycle regulating proteins responsible for mediating
      G1-S progression, such as p21(Waf1/Cip1) and p27(Kip1), Cdk2 and PCNA, p-ERK1/2.
      These findings suggest that LRRC4 may play an important role in maintaining
      normal function and suppressing tumorigenesis in the central nervous system.

PMID- 15967443
TI  - Quinolinate synthetase, an iron-sulfur enzyme in NAD biosynthesis.
AB  - Nicotinamide adenine dinucleotide (NAD) plays a crucial role as a cofactor in
      numerous essential redox biological reactions. NAD derives from quinolinic acid
      which is synthesized in Escherichia coli from L-aspartate and dihydroxyacetone
      phosphate (DHAP) as the result of the concerted action of two enzymes, L
      aspartate oxidase (NadB) and quinolinate synthetase (NadA). We report here the
      characterization of NadA protein from E. coli. When anaerobically purified, the
      isolated soluble protein contains 3-3.5 iron and 3-3.5 sulfide/polypeptide chain.
      Mossbauer spectra of the 57Fe-protein revealed that the majority of the iron is
      in the form of a (4Fe-4S)2+ cluster. An enzymatic assay for quinolinate
      synthetase activity was set up and allowed to demonstrate that the cluster is
      absolutely required for NadA activity. Exposure to air leads to degradation of
      the cluster and inactivate enzyme.

PMID- 15967444
TI  - Induction of 15-lipoxygenase-1 impairs expression of HIV-1 receptors CD4 and
      CXCR4 in monocytic cells.
AB  - The lipoxygenase pathway of immunocompetent cells has been related to HIV
      infection and interleukins-4 and -13 have been described as major regulators of
      this metabolic route. To explore whether 15-lipoxygenase1 expression might impact
      the responsiveness of monocytic cells for HIV we induced expression of this
      enzyme by two independent ways (stable transfection of U937 cells and culturing
      of blood monocytes in vitro in the presence of granulocyte/monocyte colony
      stimulating factor and interleukin 4) and assayed the cellular content of the two
      HIV-1 receptors CD4 and CXCR4 (CD184) by real time RT-PCR and fluorescence
      activated cell sorting. Wild-type U937 cells express CD4 and CXCR4 at high levels
      and expression was not altered when the cells were transfected with control
      plasmids. In contrast, expression of these proteins was strongly reduced when the
      cells were stably transfected with 15-lipoxygenase1. Similar effects were
      observed when blood monocytes were cultured in the presence of
      granulocyte/monocyte colony stimulating factor and interleukin-4. Under these
      conditions strong overexpression of 15-lipoxygenase1 was paralleled by
      downregulation of CD4 and CXCR4. Since these surface proteins are essential for
      the binding of T-tropic HIV-1 strains expression of 15-lipoxygenase1 may confer
      resistance against HIV infection to monocytic cells.

PMID- 15967445
TI  - Downregulation of Ski and SnoN co-repressors by anisomycin.
AB  - Proteasome pathway regulates TGF-beta signaling; degradation of activated Smad2/3
      and receptors turns TGF-beta signal off, while degradation of negative modulators
      such as Ski and SnoN maintains the signal. We have found that anisomycin is able
      to downregulate Ski and SnoN via proteasome as TGF-beta does, but through a
      mechanism independent of Smad activation. The mechanism used by anisomycin to
      downregulate Ski and SnoN is also independent of MAPK activation and protein
      synthesis inhibition. TGF-beta signal was the only pathway described causing Ski
      and SnoN degradation, thus this new effect of anisomycin on endogenous Ski and
      SnoN proteins suggests alternative processes to downregulate these negative
      modulators of TGF-beta signaling.

PMID- 15967446
TI  - Seabream antiquitin: molecular cloning, tissue distribution, subcellular
      localization and functional expression.
AB  - Subsequent to our earlier report on the first purification of antiquitin protein
      from seabream liver and demonstration of its enzymatic activity [FEBS Letters 516
      (2002) 183-186], we report herein the cloning of its full-length cDNA sequence.
      The open reading frame encodes a protein of 511 amino acids. Results of RT-PCR
      indicate that antiquitin is highly expressed in both the seabream liver and
      kidney. Transfection studies in cultured eukaryotic cells provided further
      evidence that it is a cytosolic protein. Bacterial expression of the enzyme was
      also performed. The purified recombinant protein was demonstrated to exhibit
      similar kinetic properties as the native enzyme.

PMID- 15967447
TI  - Hormonal, behavioral, and thermoregulatory responses to bacterial
      lipopolysaccharide in captive and free-living white-crowned sparrows (Zonotrichia
      leucophrys gambelii).
AB  - Exposing vertebrates to pathogenic organisms or inflammatory stimuli, such as
      bacterial lipopolysaccharide (LPS), activates the immune system and triggers the
      acute phase response. This response involves fever, alterations in neuroendocrine
      circuits, such as hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) axes,
      and stereotypical sickness behaviors that include lethargy, anorexia, adipsia,
      and a disinterest in social activities. We investigated the hormonal, behavioral,
      and thermoregulatory effects of acute LPS treatment in a seasonally breeding
      songbird, the white-crowned sparrow (Zonotrichia leucophrys gambelii) using
      laboratory and field experiments. Captive male and female sparrows were housed on
      short (8L:16D) or long (20L:4D) day lengths and injected subcutaneously with LPS
      or saline (control). LPS treatment activated the HPA axis, causing a rapid
      increase in plasma corticosterone titers over 24 h compared to controls.
      Suppression of the HPG axis occurred in long-day LPS birds as measured by a
      decline in luteinizing hormone levels. Instead of a rise in body temperature, LPS
      injected birds experienced short-term hypothermia compared to controls. Birds
      treated with LPS decreased activity and reduced food and water intake, resulting
      in weight loss. LPS males on long days experienced more weight loss than LPS
      males on short days, but this seasonal effect was not observed in females. These
      results paralleled seasonal differences in body condition, suggesting that
      modulation of the acute phase response is linked to energy reserves. In free
      living males, LPS treatment decreased song and several measures of territorial
      aggression. These studies highlight immune-endocrine-behavior interrelationships
      that may proximately mediate life-history tradeoffs between reproduction and
      defense against pathogens.

PMID- 15967448
TI  - Sex selection: treating different cases differently.
AB  - This paper contrasts ethical approaches to sex selection in countries where
      discrimination against women is pervasive, resulting in selection against girl
      children, and in countries where there is less general discrimination and couples
      do not prefer children of either sex. National sex ratio imbalances where
      discrimination against women is common have resulted in laws and policies, such
      as in India and China, to deter and prevent sex selection. Birth ratios of
      children can be affected by techniques of prenatal sex determination and
      abortion, preconception sex selection and discarding disfavored embryos, and
      prefertilization sperm sorting, when disfavored sperm remain unused. Incentives
      for son preference are reviewed, and laws and policies to prevent sex selection
      are explained. The elimination of social, economic and other discrimination
      against women is urged to redress sex selection against girl children. Where
      there is no general selection against girl children, sex selection can be allowed
      to assist families that want children of both sexes.

PMID- 15967449
TI  - Endosonographic characteristics of the anal sphincter complex in primigravid Sri
      Lankan women.
AB  - OBJECTIVE: To determine the endosonographic anatomy of the anal sphincter complex
      in primigravid Sri Lankan women. METHOD: This is an observational study of 95
      primigravid women admitted to an antenatal ward. They were examined using anal
      endosonography and data from subjects without sphincter injury were analyzed to
      describe anal sphincter morphology. Individual anal canal components were
      measured at defined levels, and the relationship of individual measurements with
      age and body mass index was calculated. RESULTS: Ninety-three of 95 women had no
      anal sphincter damage. The puborectalis sling (mean 5.5 mm, S.D. 0.77) forms the
      upper most border of the sphincter complex. The mean width of the deep external
      sphincter was 4.3 mm (S.D. 0.61); that of the superficial external sphincter was
      4.5 mm (S.D. 0.56); and that of the internal anal sphincter at the mid anal canal
      was 2.1 mm (S.D. 0.21). The intersphincteric space (mean 2.1 mm, S.D. 0.26) could
      be distinguished sonographically in all subjects. The mean width of the anterior
      ring of the subcutaneous component was 3.8 mm (S.D. 1.01). The perineal body was
      sonographically identified in 60%. CONCLUSION: A set of normal values for the
      anal sphincter components in Sri Lankan primigravid women was established.

PMID- 15967450
TI  - Intravaginal misoprostol 600 microg and 800 microg for the treatment of early
      pregnancy failure.
AB  - OBJECTIVE: To compare the respective effectiveness and safety of 600 microg and
      800 microg of intravaginal misoprostol for complete abortion in cases of early
      pregnancy failure (occurring in the first 12 weeks). METHOD: A total of 114 women
      with a diagnosis of early pregnancy failure made by transvaginal ultrasonography
      at Rajavithi Hospital between November 25, 2002 and July 31, 2003, were assigned
      randomly to 2 groups of equal size. In one group the women received 600 microg of
      misoprostol and in the other 800 microg of misoprostol intravaginally. RESULTS:
      The rate of complete abortion within 24 h was significantly higher in the group
      that received 800 microg of misoprostol (68.4%) than in the other group (45.6%)
      (P<0.05). There were no significant differences between the 2 groups regarding
      time interval between misoprostol insertion and complete abortion or side
      effects. CONCLUSION: Intravaginal misoprostol 800 microg is significantly more
      effective than vaginal misoprostol 600 microg for the termination of an early
      pregnancy failure, with no significant differences in side effects.

PMID- 15967451
TI  - Crossing cultures: the lived experience of Jordanian graduate students in
      nursing: a qualitative study.
AB  - This qualitative phenomenologic study explores the meaning of crossing cultures
      as experienced by Jordanian graduate students in nursing. Seven male and female
      students participated in conversations and journals regarding their experiences
      in the academic, social and professional realms of an American culture at a
      private, mid-Atlantic university. An analysis of the text revealed an overarching
      theme, "metamorphosis of self." Events leading to the metamorphosis included
      being chosen, experiencing a time full of memories, feeling bombarded with
      stimuli and "looking to do something" as professional nurses in Jordan.

PMID- 15967452
TI  - Caregiver's burden, depression and support as predictors of post-stroke
      depression: a cross-sectional survey.
AB  - To examine the effects of caregiver's burden, depression, and support on post
      stroke depression (PSD), cross-sectional data were obtained from an epidemiologic
      survey of 225 stroke survivors and their caregivers living in Seoul, Korea.
      Multivariate analyses showed that, taking the clinical status of patients into
      account, caregiver's burden, depression and support were related to higher PSD.
      Perceived burden exerts adverse effects on PSD through its influence on the
      depression in caregivers. Hence, the care of stroke survivors that incorporates
      the care of caregivers is likely to reduce the risk of post-stroke depression in
      patients.

PMID- 15967453
TI  - Methodological triangulation showed the poorest quality of life in the youngest
      people following treatment of coronary artery disease: a longitudinal study.
AB  - The purpose of the longitudinal study was to describe, explain and understand the
      subjective health related quality of life (HRQoL) and life course of people
      (N=280) with coronary artery disease (CAD) during the period following the onset
      of the disease, the process of therapy and the period of rehabilitation.
      Methodological triangulation was used in this research. The significance of the
      results obtained with quantitative and qualitative methods was evaluated by means
      of meta-analysis. A longitudinal quantitative study was undertaken through the
      year after the treatments (medication, balloon angioplasty or bypass surgery),
      and 19 persons attended thematic interviews 1 year after the treatments carried
      out in their homes. The results of quantitative analysis showed that the male and
      female CAD patients in the youngest age group had the poorest HRQoL. Although,
      the patients average HRQoL improved on the dimensions of pain, energy and
      mobility, it deteriorated on the dimensions of social isolation, sleep and
      emotional reactions. From the viewpoint of methodological triangulation, the most
      significant finding was that the qualitative approach provided an explanation for
      the poor psychosocial HRQoL obtained by the quantitative approach, showing the
      crucial factor to be age and age-related aspects of the life situation.
      Interviews and the method of phenomenological psychology helped to gain insight
      into the informants' situational experience of HROoL and life course, which was
      not detectable with a questionnaire.

PMID- 15967454
TI  - 'Zuoyuezi' after caesarean in China: an interview survey.
AB  - While studying caesarean decision-making in China, the increasing popularity of
      'zuoyuezi' emerged. This paper addresses this development, the reasons and
      implications. We tape-recorded semi-structured interviews in three industrial
      cities in China. The three groups of informants comprised women in the first-week
      after caesarean, women eight months after caesarean and health-workers/others.
      Mandarin or local dialects were used. The data were transcribed and analysed in
      Chinese and then selected quotes were translated into English. We found that the
      re-emergence and social modification of zuoyuezi is closely associated with the
      rising caesarean rate. This custom has been regarded as a crucial rite-of-passage
      for the woman's recovery and transition to motherhood after childbirth. Its
      particular importance after caesarean became apparent in this study. Conclusions
      are drawn about the place of ritual and tradition in 21st century China.

PMID- 15967455
TI  - Domestic violence against women in Taiwan: their life-threatening situations,
      post-traumatic responses, and psycho-physiological symptoms: an interview study.
AB  - The purpose of this study is to examine the following three aspects of domestic
      violence by men against women, and to look for possible correlations between
      them: life-threatening situations, post-traumatic responses, and psycho
      physiological symptoms. A survey interview was used to collect data on abused
      women recruited from the Kaohsiung area in southern Taiwan. 109 out of 127
      subjects completed the structured questionnaires. The findings showed that the
      medium- and high-risk groups of life-threatening situations accounted for 82.6%
      of all subjects, and 93.6% of all subjects were in a high score group of post
      traumatic responses. Among the 10 symptom dimensions of psycho-physiological
      symptoms, anxiety had the highest standardized mean score, followed by obsession,
      depression, and somatization. The life-threatening situations had significant
      positive correlation with the overall post-traumatic responses, the responses of
      intrusion, and the general severity index (GSI). Overall post-traumatic
      responses, intrusion, and avoidance were all positively associated with GSI. This
      study provides evidence to healthcare professionals that they should not only
      treat the physical injuries of abused women, but must also learn how to assess
      and adequately attend to their mental health problems.

PMID- 15967456
TI  - Effects of dopamine on juvenile hormone metabolism and fitness in Drosophila
      virilis.
AB  - The effects of dopamine (DA) on juvenile hormone (JH) metabolism and fitness
      (estimated as fecundity and viability levels under heat stress (38 degrees C)) in
      Drosophila virilis have been studied. An increase of DA level obtained by feeding
      with DA reduced fitness of wild-type (wt) flies under stress, and decreased JH
      degradation in young wt females while increasing it in sexually mature wt
      females. A decrease in DA levels resulted from 3-iodo-tyrosine treatment and
      caused a decrease in JH degradation in sexually mature wt and heat sensitive (hs)
      mutant females (DA level in hs females is twice as high in wt females). A
      dramatic decrease in viability under stress and fecundity under normal conditions
      in wt, but not hs, females was observed. 3-iodo-tyrosine treatment also reduced
      the number of oocytes at stages 8-14, delayed oocyte transition to stage 10 and
      resulted in the accumulation of mature eggs in wt females. It delayed maturation
      of wt, but not hs, males as well, but did not affect their fertility. This
      advances our understanding of the regulation of JH metabolism by DA in Drosophila
      and suggests a crucial role for the basal DA level in fitness.

PMID- 15967457
TI  - Roles of the mushroom bodies in olfactory learning and photoperiodism in the blow
      fly Protophormia terraenovae.
AB  - Mushroom bodies (MBs) in Protophormia terraenovae were ablated by hydroxyurea
      (HU) treatment to larvae just after hatching in order to examine roles of the MBs
      in olfactory learning and photoperiodism. In all individuals the structures of
      the alpha, beta, and gamma lobes, the pedunculi, and the calyces of the MB were
      not found after HU treatment. The other structures of the brain were not
      obviously damaged. The volumes of both the antennal lobes and the central
      complex, however, were smaller in the HU-treated flies than those in the control
      flies. The HU-treated and non-treated flies were tested for their appetitive
      olfactory learning ability and photoperiodism. In the olfactory learning
      paradigm, an odor of methylsalicylate or coumarin was paired with a reward of
      sucrose. The non-treated flies learned to associate both odors with the reward,
      but the HU-treated flies did not. In the test for photoperiodism, both the HU
      treated and non-treated flies responded to photoperiod. Both groups of flies
      developed ovaries under long-day conditions but entered diapause under short-day
      conditions. The results imply that the MBs are indispensable for olfactory
      learning but not for photoperiodism, and that storage of daily cycles of
      photoperiodic information occurs by a neural system other than the MBs.

PMID- 15967458
TI  - Simulation and experiment conspire to reveal cryptic intermediates and a slide
      from the nucleation-condensation to framework mechanism of folding.
AB  - There is a change from three-state to two-state kinetics of folding across the
      homeodomain superfamily of proteins as the mechanism slides from framework to
      nucleation-condensation. The tendency for framework folding in this family
      correlates with inherent helical propensity. The cellular myeloblastis protein (c
      Myb) falls in the mechanistic transition region. An earlier, preliminary report
      of protein engineering experiments and molecular dynamics simulations (MD) showed
      that the folding mechanism for this protein has aspects of both the nucleation
      condensation and framework models. In the more in-depth analysis of the MD
      trajectories presented here, we find that folding may be attributed to both of
      these mechanisms in different regions of the protein. The folding of the loop,
      middle helix, and turn is best described by nucleation-condensation, whereas
      folding of the N and C-terminal helices may be described by the framework model.
      Experimentally, c-Myb folds by apparent two-state kinetics, but the MD
      simulations predict that the kinetics hide a high-energy intermediate. We
      stabilized this hypothetical folding intermediate by deleting a residue (P174) in
      the loop between its second and third helices, and the mutant intermediate is
      long-lived in the simulations. Equilibrium and kinetic experiments demonstrate
      that folding of the DeltaP174 mutant is indeed three-state. The presence and
      shape of the intermediate observed in the simulations were confirmed by small
      angle X-ray scattering experiments.

PMID- 15967459
TI  - Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin
      lymphoma-derived and primary effusion lymphoma cell lines.
AB  - Hodgkin and Reed-Sternberg (HRS) cells of classical Hodgkin lymphoma (cHL) and
      primary effusion lymphoma (PEL) are derived from germinal center (GC) and post-GC
      B cells, respectively. Neither express many of the B cell genes or surface
      markers typically expressed by other GC-derived B cell lymphomas or normal B
      cells. This loss of B cell gene expression is not due to a lack of essential
      transcription factors, as studies have shown that the ectopic expression of
      missing transcription factors failed to reactivate endogenous target genes. These
      results implicate epigenetic mechanisms extinguishing B cell gene expression.
      Silenced endogenous B cell genes representing a surface receptor, B29 (Igbeta,
      CD79b), a signaling molecule, TCL1, and a transcription factor, Bob1 (OCA-B, OBF
      1), were reactivated by 5-aza-2'-deoxycytidine, indicating that gene silencing in
      HRS and PEL cells is due to DNA methylation. Genomic bisulfite sequencing
      corroborated this prediction and revealed three distinct patterns of methylation
      for the silenced B29 and TCL1 promoters. These distinct patterns consisted of 5'
      promoter CpG methylation alone, 5' and 3' promoter CpG methylation sparing sites
      in the central cores, and complete CpG methylation throughout the promoter
      regions. The silenced Bob1 promoter showed one pattern of dense CpG methylation
      at essentially all sites. These consistent patterns predict that, although gene
      silencing in many HRS and PEL cells mimics appropriate gene silencing, in some
      cases of complete CpG methylation throughout entire promoters both the activation
      and targeting of methylation is abnormal.

PMID- 15967460
TI  - Negative cooperativity of uric acid binding to the transcriptional regulator HucR
      from Deinococcus radiodurans.
AB  - Members of the MarR family of winged helix transcriptional regulators have been
      shown to regulate multidrug and oxidative stress response, pathogenesis, and
      catabolism of aromatic compounds. Many respond to anionic lipophilic compounds in
      their capacity to bind DNA, and the co-crystal structure of MarR bound to
      salicylate revealed two ligand-binding pockets, SAL-A and SAL-B. The MarR
      homolog, HucR, from Deinococcus radiodurans has been shown to repress expression
      of a predicted uricase, and DNA-binding by HucR is antagonized by uric acid, the
      substrate of uricase. We provide a biochemical investigation of DNA-binding and
      uric acid-binding by HucR. Equilibrium analytical ultracentrifugation indicates
      that HucR exists as a dimer. Intrinsic fluorescence spectra suggest that the
      association of the HucR dimer with its cognate DNA involves conformational
      flexibility in the globular interior and/or dimerization domain of the protein,
      and near-UV circular dichroism spectra indicate a concomitant change in the
      helical twist of the DNA duplex. DNA-binding affinity, measured by
      electrophoretic mobility-shift assays, for HucR mutants bearing single amino acid
      substitutions suggests the importance of the beta-hairpin "wing" in DNA binding.
      Analysis of intrinsic fluorescence spectra demonstrates that uric acid induces
      conformational changes in HucR and binds with an apparent K(d)=11.6(+/-3.7)muM
      and a Hill coefficient of 0.7+/-0.1, indicating negative cooperativity.
      Fluorescence and DNA-binding properties of the HucR variants indicate that SAL-A
      is a low-affinity, uric acid-binding site and that negative cooperativity exists
      between homologous, high-affinity sites. The conservation of residues comprising
      site SAL-A suggests that it is a low-affinity, ligand-binding site in MarR
      homologs. Mechanistic considerations suggest that HucR is regulated by uric acid
      to maintain optimal cellular levels of this scavenger of free radicals in
      response to oxidative stress and DNA damage.

PMID- 15967461
TI  - The activation mechanism of Hsp26 does not require dissociation of the oligomer.
AB  - Small heat shock proteins (sHsps) are molecular chaperones that specifically bind
      non-native proteins and prevent them from irreversible aggregation. A key trait
      of sHsps is their existence as dynamic oligomers. Hsp26 from Saccharomyces
      cerevisiae assembles into a 24mer, which becomes activated under heat shock
      conditions and forms large, stable substrate complexes. This activation coincides
      with the destabilization of the oligomer and the appearance of dimers. This and
      results from other groups led to the generally accepted notion that dissociation
      might be a requirement for the chaperone mechanism of sHsps. To understand the
      chaperone mechanism of sHsps it is crucial to analyze the relationship between
      chaperone activity and stability of the oligomer. We generated an Hsp26 variant,
      in which a serine residue of the N-terminal domain was replaced by cysteine. This
      allowed us to covalently crosslink neighboring subunits by disulfide bonds. We
      show that under reducing conditions the structure and function of this variant
      are indistinguishable from that of the wild-type protein. However, when the
      cysteine residues are oxidized, the dissociation into dimers at higher
      temperatures is no longer observed, yet the chaperone activity remains
      unaffected. Furthermore, we show that the exchange of subunits between Hsp26
      oligomers is significantly slower than substrate aggregation and even inhibited
      in the presence of disulfide bonds. This demonstrates that the rearrangements
      necessary for shifting Hsp26 from a low to a high affinity state for binding non
      native proteins occur without dissolving the oligomer.

PMID- 15967462
TI  - MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly:
      towards understanding MURF-dependent muscle ubiquitination.
AB  - MURF-1, MURF-2 and MURF-3 are a specific class of RING finger proteins that are
      expressed in striated muscle tissues. MURF-1 has been suggested to act as an
      ubiquitin ligase, thereby controlling proteasome-dependent degradation of muscle
      proteins. Here, we performed yeast two-hybrid (YTH) screens of skeletal muscle
      cDNA libraries with MURF-1 baits to identify potential myocellular targets of
      MURF-1-dependent ubiquitination. This identified eight myofibrillar proteins as
      binding partners of MURF-1: titin, nebulin, the nebulin-related protein NRAP,
      troponin-I (TnI), troponin-T (TnT), myosin light chain 2 (MLC-2), myotilin and T
      cap. YTH mating studies with MURF-1,2,3 baits indicated that these eight
      myofibrillar proteins are all targeted redundantly by both MURF-1 and MURF-2.
      Western blot studies on cardiac tissues from wild-type and MURF-1-deficient mice
      suggested that titin and nebulin were ubiquitinated at similar levels, and MLC-2
      and TnI at reduced levels in MURF-1 KO mice. Mapping of the TnI and titin binding
      sites on MURF-1 peptide scans demonstrated their binding to motifs highly
      conserved between MURF-1 and MURF-2. Our data are consistent with a model in
      which MURF-1 and MURF-2 together target a specific set of myofibrillar proteins
      redundantly, most likely to control their ubiquitination-dependent degradation.
      Finally, our YTH screens identified the interaction of MURF-1 with 11 enzymes
      required for ATP/energy production in muscle including the mitochondrial ATP
      synthase and cytoplasmic creatine kinase. These data raise the possibility that
      MURF-1 may coordinately regulate the energy metabolism of mitochondrial and
      cytoplasmic compartments.

PMID- 15967463
TI  - Toxoplasma gondii Hsp90 is a potential drug target whose expression and
      subcellular localization are developmentally regulated.
AB  - Two replicative forms characterize the asexual cycle of the protozoan parasite
      Toxoplasma gondii: rapidly growing tachyzoites and slowly dividing encysted
      bradyzoites. The mechanisms that regulate the transition between these two stages
      are not clearly understood. However, stress inducers that also activate heat
      shock protein expression can trigger formation of bradyzoites in vitro. Here, we
      studied the association of the T.gondii Hsp90 with modulation of parasite
      differentiation and response to stress stimuli using RH DeltaUPRT parasites and
      the cystogenic strain ME49 and a clone derivative of that strain, PK. Our results
      show that Hsp90 transcript and protein levels increase under stress or bradyzoite
      differentiation conditions. Moreover, fluorescence microscopy studies revealed
      that Hsp90 is present in the cytosol of tachyzoites and both in the nucleus and
      cytosol of mature bradyzoites, suggesting a correlation between its subcellular
      organization and these two developmental stages. To further characterize the role
      for Hsp90 in bradyzoite differentiation, T.gondii tachyzoite mutants that are
      defective in differentiation showed the same staining pattern as tachyzoites
      under differentiation conditions. In addition, geldanamycin, a benzoquinone
      ansamycin antibiotic capable of binding and disrupting the function of Hsp90,
      blocked conversion both from the tachyzoite to bradyzoite and the bradyzoite to
      tachyzoite stage, suggesting an essential role for this protein in the regulation
      of stage interconversion. These results thus suggest Hsp90 may play a role in
      stage switch.

PMID- 15967464
TI  - Sequence correlations between Cro recognition helices and cognate O(R) consensus
      half-sites suggest conserved rules of protein-DNA recognition.
AB  - The O(R) regions from several lambdoid bacteriophages contain the three
      regulatory sites O(R)1, O(R)2 and O(R)3, to which the Cro and CI proteins can
      bind. These sites show imperfect dyad symmetry, have similar sequences, and
      generally lie on the same face of the DNA double helix. We have developed a
      computational method, which analyzes the O(R) regions of additional phages and
      predicts the location of these three sites. After tuning the method to predict
      known O(R) sites accurately, we used it to predict unknown sites, and ultimately
      compiled a database of 32 known and predicted O(R) binding site sets. We then
      identified sequences of the recognition helices (RH) for the cognate Cro proteins
      through manual inspection of multiple sequence alignments. Comparison of Cro RH
      and consensus O(R) half-site sequences revealed strong one-to-one correlations
      between two amino acids at each of three RH positions and two bases at each of
      three half-site positions (H1-->2, H3-->5 and H6-->6). In each of these three
      cases, one of the two amino acid/base-pairings corresponds to a contact observed
      in the crystal structure of a lambda Cro/consensus operator complex. The
      alternate amino acid/base combinations were rationalized using structural models.
      We suggest that the pairs of amino acid residues act as binary switches that
      efficiently modulate specificity for different consensus half-site variants
      during evolution. The observation of structurally reasonable amino acid-to-base
      correlations suggests that Cro proteins share some common rules of recognition
      despite their functional and structural diversity.

PMID- 15967466
TI  - tmRNA-induced release of messenger RNA from stalled ribosomes.
AB  - A ribosome stalled on a truncated mRNA in the eubacterial cell can be rescued by
      tmRNA via a process called trans-translation. We demonstrate here that release of
      truncated mRNAs from stalled ribosomes accelerates significantly already after
      trans-peptidation following tmRNA binding to the ribosome. However, rapid release
      of truncated mRNA requires EF-G-dependent translocation of peptidyl-tmRNA from
      the A to the P site of the ribosome. We show also that the rate of mRNA release
      before and after peptidyl-tmRNA translocation correlates well with the rate of
      dissociation of deacylated tRNA, indicating that mRNA is retained on the ribosome
      mainly through codon:anticodon interaction with tRNA. The rate of mRNA release is
      reduced for mRNAs with strong Shine-Dalgarno (SD)-like sequences in the vicinity
      of the truncation site as well as for mRNAs with long 3' extensions downstream
      from the P-site codon. The reduced rate of release in the former case was due to
      a persisting SD-anti SD interaction between mRNA and the ribosome.

PMID- 15967465
TI  - Binding linkage in a telomere DNA-protein complex at the ends of Oxytricha nova
      chromosomes.
AB  - Alpha and beta protein subunits of the telomere end binding protein from
      Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a
      protective cap at the ends of chromosomes. We tested how protein-protein
      interactions seen in the co-crystal structure relate to DNA binding through use
      of fusion proteins engineered as different combinations of domains and subunits
      derived from OnTEBP. Joining alpha and beta resulted in a protein that bound
      single strand telomere DNA with high affinity (K(D-DNA)=1.4 nM). Another fusion
      protein, constructed without the C-terminal protein-protein interaction domain of
      alpha, bound DNA with 200-fold diminished affinity (K(D-DNA)=290 nM) even though
      the DNA-binding domains of alpha and beta were joined through a peptide linker.
      Adding back the alpha C-terminal domain as a separate protein restored high
      affinity DNA binding. The binding behaviors of these fusion proteins and the
      native protein subunits are consistent with cooperative linkage between protein
      association and DNA-binding equilibria. Linking DNA-protein stability to protein
      protein contacts at a remote site may provide a trigger point for DNA-protein
      disassembly during telomere replication when the single strand telomere DNA must
      exchange between a very stable OnTEBP complex and telomerase.

PMID- 15967467
TI  - Probing the "annealing" mechanism of GroEL minichaperone using molecular dynamics
      simulations.
AB  - Although the intact chaperonin machinery is needed to rescue natural substrate
      proteins (SPs) under non-permissive conditions the "minichaperone" alone,
      containing only the isolated apical domain of GroEL, can assist folding of a
      certain class of proteins. To understand the annealing function of the
      minichaperone, we have carried out molecular dynamics simulations in the NPT
      ensemble totaling 300ns for four systems; namely, the isolated strongly binding
      peptide (SBP), the minichaperone, and the SBP and a weakly binding peptide (WBP)
      in complex with the minichaperone. The SBP, which is structureless in isolation,
      adopts a beta-hairpin conformation in complex with the minichaperone suggesting
      that favorable non-specific interactions of the SPs confined to helices H and I
      of the apical domains can induce local secondary structures. Comparison of the
      dynamical fluctuations of the apo and the liganded forms of the minichaperone
      shows that the stability (needed for SP capture) involves favorable hydrophobic
      interactions and hydrogen bond network formation between the SBP and WBP, and
      helices H and I. The release of the SP, which is required for the annealing
      action, involves water-mediated interactions of the charged residues at the ends
      of H and I helices. The simulation results are consistent with a transient
      binding release (TBR) model for the annealing action of the minichaperone.
      According to the TBR model, SP annealing occurs in two stages. In the first stage
      the SP is captured by the apical domain. This is followed by SP release (by
      thermal fluctuations) that places it in a different region of the energy
      landscape from which it can partition rapidly to the native state with
      probability Phi or be trapped in another misfolded state. The process of binding
      and release can result in enhancement of the native state yield. The TBR model
      suggests "that any cofactor that can repeatedly bind and release SPs can be
      effective in assisting protein folding." By comparing the structures of the non
      chaperone alpha-casein (which has no sequence similarity with the apical domain)
      and the minichaperone and the hydrophobicity profiles we show that alpha-casein
      has a pair of helices that have similar sequence and structural profiles as H and
      I. Based on this comparison we identify residues that stabilize (destabilize)
      alpha-casein-protein complexes. This suggests that alpha-casein assists folding
      by the TBR mechanism.

PMID- 15967468
TI  - Recovery and prognosticators of paralysis in West Nile virus infection.
AB  - Previous studies have demonstrated that lesions of the anterior horn motor
      neurons are the primary pathology in patients with paralysis due to West Nile
      virus (WNV) infection. To characterize recovery and identify prognostic factors
      for the recovery of paralysis, we investigated 11 patients with electrophysiology
      testing and muscle biopsy, and one with autopsy. We found that limb weakness was
      markedly asymmetric and differed between upper and lower extremities, suggesting
      focal or segmental involvement of the spinal cord anterior horn. This was
      supported by segmental depletion of spinal motor neurons at autopsy. Clinical
      recovery was variable during a 21-month follow-up period. To explain variability,
      we performed motor unit number estimation (MUNE) in six patients. MUNE values and
      strength were correlated in tested muscles. We also detected motor nerve terminal
      damages in muscle biopsies, suggesting another possible mechanism for transient
      weakness and variable recovery. We conclude that the type of pathological lesions
      may vary in paralytic WNV infection, and different degrees or combinations of
      motor neuron loss and motor nerve terminal changes may account for the observed
      degrees of weakness and recovery.

PMID- 15967469
TI  - Reversal of p-glycoprotein-mediated multidrug resistance by CJX1, an amlodipine
      derivative, in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.
AB  - P-glycoprotein-mediated drug efflux can yield a multidrug resistance (MDR)
      phenotype that is associated with a poor response to cancer chemotherapy.
      Development of safe and effective MDR reversing agents is an important approach
      in the clinic. The aim of this study was to observe the effects of CJX1, an
      amlodipine derivative, on the inhibition of P-gp function and P-gp-mediated MDR
      in K562/DOX cells and parental K562 cells. Based on the flow cytometric
      technology, the uptake, accumulation and efflux of rhodamine123 (Rh123) were
      detected in these cells by measuring Rh123-associated mean fluorescence intensity
      (MFI). The effects of CJX1 on the doxorubicin cytotoxicity were evaluated by
      assaying for MTT (3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide)
      reduction and the reversal fold (RF) values. The DNA content, percentage of
      apoptosis and cell cycle analysis were monitored with flow cytometry.
      Intracellular accumulation of doxorubicin was also assessed by the determination
      of doxorubicin-associated MFI. Verapamil was employed as a comparative agent.
      Incubation of K562/DOX cells with CJX1 caused a marked increase in uptake and a
      notable decrease in efflux of Rh123, No such results were found in parental K562
      cells. The inhibitory effect of the agent of P-gp function was reversible, but it
      persisted at least for 90 min after removal of 2.5 microM CJX1 from incubation
      medium. The doxorubicin-induced cytotoxicity, apoptosis and cell cycle
      perturbations were significantly potentiated by CJX1. The intracellular
      accumulation of doxorubicin was enhanced in the presence of various
      concentrations of CJX1. The CJX1 exhibited potent effects in vitro in the
      reversal of P-gp-mediated MDR, suggesting that the compound may become a
      candidate of effective MDR reversing agent in cancer chemotherapy.

PMID- 15967470
TI  - Development of a coculture system and use of confocal laser fluorescent
      microscopy to study human microvascular endothelial cell and mural cell
      interaction.
AB  - In the present study, human myometrial microvascular endothelial cells (HMMEC)
      were cocultured with human vascular smooth muscle cells (VSMC) labeled with
      fluorescent dyes to examine their morphological interaction using confocal laser
      fluorescent microscopy. HMMEC and VSMC labeled with fluorescent green and red
      dyes, respectively, attached to opposite sides of polyethyleneterephthalate
      membranes and remained viable for up to 96 h. In defined medium, 5%+/-3% of the
      VSMC cytoplasmic processes and 71%+/-17% of the HMMEC processes extended
      completely across the 13 microm thickness of the transmembrane. However, 41%+/
      21% of the VSMC projections and 10%+/-3% of the HMMEC processes that traversed
      the membrane made contact with the opposing cell type. In cocultures incubated
      with angiopoietin-1 (Ang-1), although the number of VSMC or HMMEC projections was
      not significantly increased, the number of VSMC extending across the membrane and
      making contact with HMMEC was increased (P<0.05) to 88%+/-2%. The results of the
      current study demonstrate that coculture of fluorescent-labeled HMMEC and VSMC on
      a semipermeable transmembrane coupled with confocal laser fluorescent microscopy
      provides an in vitro experimental model to study morphological association of
      microvascular endothelial cells with mural cells. We propose that this system
      will greatly facilitate study of remodeling of the microvasculature in various
      organ systems.

PMID- 15967471
TI  - Competitive divergence in non-random mating populations.
AB  - A haploid model of frequency-dependent selection and assortative mating is
      introduced and analyzed for the case of a single multiallelic autosomal locus.
      Frequency-dependent selection is due to intraspecific competition mediated by a
      quantitative character under stabilizing or directional selection. Assortment is
      induced by the same trait. We analyze the equilibrium structure and the local
      stability properties of all possible equilibria. In the limit of weak selection
      we obtain global stability properties by finding a Lyapunov function. We provide
      necessary and sufficient conditions for the maintenance of polymorphism in terms
      of the strength of stabilizing selection, intraspecific competition and
      assortment. Our results also include criteria for the ability of extreme types to
      invade the population. Furthermore, we study the occurrence of disruptive
      selection and provide necessary and sufficient conditions for intraspecific
      divergence to occur.

PMID- 15967472
TI  - Perceptual learning of Gabor orientation identification in visual periphery:
      complete inter-ocular transfer of learning mechanisms.
AB  - We combined the external noise paradigm, the Perceptual Template Model approach,
      and transfer tests to investigate the mechanisms and eye-specificity of
      perceptual learning of Gabor orientation in visual periphery. Coupled with a
      fixation task, discriminating a 5 from an S in a rapid small character string at
      fixation, contrast thresholds were estimated for each of eight external noise
      levels at two performance criteria using 3/1 and 2/1 staircases. Perceptual
      learning in one eye was measured over 10 practice sessions, followed by five
      sessions of practice in the new eye to assess transfer. We found that monocular
      learning improved performance (reduced contrast thresholds) with virtually equal
      magnitude across a wide range of external noise levels with no significant change
      in central task performance. Based on measurements of learning effects at two
      performance criterion levels, we identified a mixture of stimulus enhancement and
      external noise exclusion as the mechanism of perceptual learning underlying the
      observed improvements. Perceptual learning in the trained eye generalized
      completely to the untrained eye. We related the transfer patterns to known
      physiology and psychophysics on orientation direction coding.

PMID- 15967473
TI  - Haloacetic acids in drinking water in the United Kingdom.
AB  - We measured concentrations of haloacetic acids (HAAs) in the water supply in
      regions covered by three water companies in the UK Approximately 30 samples in
      each region were obtained for analysis of both THMs and HAAs to assess the levels
      of HAAs and the relationship between HAAs and THMs, temperature, pH, free and
      total chlorine. We have found that there is a range of HAA levels in drinking
      water with the means ranging from 35-95mug/l and a maximum concentration of
      244mug/l. In two out of the three regions there was a high correlation between
      total THMs and total HAAs, but whereas the HAA and THM levels in one of these
      companies were approximately equal, in another company the HAA levels were 3-4
      times higher than the THM levels. In the third region there was no correlation
      between total THMs and total HAAs even though the average levels were
      approximately equal. The ratio of total THM and total HAAs levels was
      significantly correlated with temperature, pH, free and total chlorine. Overall
      total THM levels are therefore not considered to be a good indicator of HAA
      levels. Epidemiological studies using total THM levels should be taking this into
      account in the interpretation of their results, and regulatory authorities when
      setting water guidelines.

PMID- 15967474
TI  - The influence of the rigidity of geosorbent organic matter on non-ideal sorption
      behaviors of chlorinated benzenes.
AB  - This study focused on evaluating the influence of the rigidity of natural organic
      matter (NOM) associated with four natural geosorbents in controlling the non
      ideal sorption behaviors of five chlorinated benzenes. Single solute sorption
      isotherms for each sorbate/sorbent combination were modeled and interpreted by
      the Freundlich sorption isotherm and the adsorption-partitioning model based on
      Polanyi-Manes theory (PM model). "Rigid" organic matter was operationally
      quantified as the fraction of carbon resistant to wet chemical oxidation (hard
      carbon) or thermal oxidation (soot carbon); atomic H/O ratios indicated a close
      correlation between the degree of reduction of the NOM and its rigidity. Sorbents
      with larger rigid carbon fractions had more non-linear sorption isotherms and
      higher organic carbon (OC) normalized sorption affinities. The size of the PM
      hole filling domain for a given sorbent was closely correlated with the extent to
      which the sorbent's affinity for chlorobenzenes exceeded predictions from a
      linear free energy relationship. Loss of some portions of the rigid character of
      the NOM domain due to the penetration of sorbate molecules (plasticization) was
      discussed as a possible contributor to the non-ideal sorption behaviors observed
      in this study. The existence of a permanently rigid NOM domain, not subject to
      plasticization under environmental conditions, was postulated as an additional
      factor determining the observed sorption behavior.

PMID- 15967475
TI  - Thi20, a remarkable enzyme from Saccharomyces cerevisiae with dual thiamin
      biosynthetic and degradation activities.
AB  - Saccharomyces cerevisiae Thi20 is a fusion protein with homology to Bacillus
      subtilis ThiD and TenA. The N-terminus of Thi20 has significant sequence homology
      to B. subtilis ThiD, while the C-terminus has homology to B. subtilis TenA.
      Incubation of Thi20 with thiamin reveals that it has thiaminase II activity, in
      addition, incubation of Thi20 with HMP (4-amino-2-methyl-5
      hydroxymethylpyrimidine) and ATP reveals that it has HMP kinase and HMP-P (4
      amino-2-methyl-5-hydroxymethylpyrimidine phosphate) kinase activity. This
      demonstrates that Thi20 is a trifunctional protein with thiamin biosynthetic and
      degradative activity.

PMID- 15967476
TI  - Optimization of a pressurization methodology for extracting pore-water.
AB  - Sediment toxicity can be assessed by conducting pore-water toxicity assays with
      standard water column organisms. Several methods have been developed for sampling
      pore-water. Centrifugation and pressurization methods are recommended when large
      volumes of pore-water are required to perform toxicity assays. Nevertheless,
      these methods involve sediment transportation and storage in laboratory, which
      can alter sediment toxicity. Therefore, an extraction method for large volumes
      that could be employed in the field site would be highly desirable. This study
      aimed to optimize and further evaluate an existing sediment pressurizing device
      with low construction costs, easy to carry and operate in the field, and
      presenting minimal chemical reactivity. The latter characteristic was achieved by
      lining the device interior with Teflon, by using large pore filters (50 microm),
      and by using an inert gas (nitrogen). Pore-water extraction efficiency and the
      toxicities of pore-water samples obtained by pressurization and by refrigerated
      centrifugation were compared. An artificial sediment (70% sand, 20% kaolin and
      10% alpha-cellulose) spiked with an alcohol (phenol), a surfactant (SDS), a metal
      (copper), an organophosphate pesticide (parathion), and a natural sediment
      contaminated with acid mine drainage, were assayed for toxicity using Microtox
      assays. Sediment pressurization was found to be as efficient to extract pore
      water as centrifugation, being more cost effective and adequate for field use.

PMID- 15967477
TI  - Soil remediation time to achieve clean-up goals I: Influence of soil water
      content.
AB  - The current models are not simple enough to allow a quick estimation of the
      remediation time. This work reports the development of an easy and relatively
      rapid procedure for the forecasting of the remediation time using vapour
      extraction. Sandy soils contaminated with cyclohexane and prepared with different
      water contents were studied. The remediation times estimated through the
      mathematical fitting of experimental results were compared with those of real
      soils. The main objectives were: (i) to predict, through a simple mathematical
      fitting, the remediation time of soils with water contents different from those
      used in the experiments; (ii) to analyse the influence of soil water content on
      the: (ii(1)) remediation time; (ii(2)) remediation efficiency; and (ii(3))
      distribution of contaminants in the different phases present into the soil matrix
      after the remediation process. For sandy soils with negligible contents of clay
      and natural organic matter, artificially contaminated with cyclohexane before
      vapour extraction, it was concluded that (i) if the soil water content belonged
      to the range considered in the experiments with the prepared soils, then the
      remediation time of real soils of similar characteristics could be successfully
      predicted, with relative differences not higher than 10%, through a simple
      mathematical fitting of experimental results; (ii) increasing soil water content
      from 0% to 6% had the following consequences: (ii(1)) increased remediation time
      (1.8-4.9h, respectively); (ii(2)) decreased remediation efficiency (99-97%,
      respectively); and (ii(3)) decreased the amount of contaminant adsorbed onto the
      soil and in the non-aqueous liquid phase, thus increasing the amount of
      contaminant in the aqueous and gaseous phases.

PMID- 15967478
TI  - Temperature dependencies of Henry's law constants and octanol/water partition
      coefficients for key plant volatile monoterpenoids.
AB  - To model the emission dynamics and changes in fractional composition of
      monoterpenoids from plant leaves, temperature dependencies of equilibrium
      coefficients must be known. Henry's law constants (H(pc), Pa m3 mol(-1) and
      octanol/water partition coefficients (K(OW), mol mol(-1)) were determined for 10
      important plant monoterpenes at physiological temperature ranges (25-50 degrees C
      for H(pc) and 20-50 degrees C for K(OW)). A standard EPICS procedure was
      established to determine H(pc) and a shake flask method was used for the
      measurements of K(OW). The enthalpy of volatilization (deltaH(vol)) varied from
      18.0 to 44.3 kJ mol(-1) among the monoterpenes, corresponding to a range of
      temperature-dependent increase in H(pc) between 1.3- and 1.8-fold per 10 degrees
      C rise in temperature. The enthalpy of water-octanol phase change varied from 
      11.0 to -23.8 kJ mol(-1), corresponding to a decrease of K(OW) between 1.15- and
      1.32-fold per 10 degrees C increase in temperature. Correlations among physico
      chemical characteristics of a wide range of monoterpenes were analyzed to seek
      the ways of derivation of H(pc) and K(OW) values from other monoterpene physico
      chemical characteristics. H(pc) was strongly correlated with monoterpene
      saturated vapor pressure (P(v)), and for lipophilic monoterpenes, deltaH(vol)
      scaled positively with the enthalpy of vaporization that characterizes the
      temperature dependence of P(v) Thus, P(v) versus temperature relations may be
      employed to derive the temperature relations of H(pc) for these monoterpenes.
      These data collectively indicate that monoterpene differences in H(pc) and K(OW)
      temperature relations can importantly modify monoterpene emissions from and
      deposition on plant leaves.

PMID- 15967479
TI  - Appropriate combination of physico-chemical methods (coagulation/flocculation and
      ozonation) for the efficient treatment of landfill leachates.
AB  - An integrated technique consisted of ozonation and coagulation/flocculation
      processes was studied, aiming to provide an efficient method for the treatment of
      stabilized/biologically pre-treated leachates, in order to reduce the organic
      pollutants' content to concentration values lower than the corresponding limits,
      imposed by the legislation. Leachates were collected from a municipal landfill
      site; samples containing around 1000 mg l(-1) COD and BOD(5)/COD ratio about 0.17
      were treated by using two different processes or combinations between them, i.e.
      ozonation, coagulation-flocculation, ozonation followed by
      coagulation/flocculation and coagulation/flocculation followed by ozonation. The
      application of single ozonation resulted to the efficient removal of color and
      organic loading, due to the respective oxidation, induced by ozonation; however,
      COD values lower than 200 mg l(-1) could be only achieved after prolonged
      reaction times and for high ozone production rates. The coagulation of leachate
      samples was studied by the addition of ferric chloride or poly-aluminum chloride
      agents at various dosages. Maximum COD removal rates (up to 72%) were achieved by
      the addition of 7 mM Fe, or of 11 mM Al respectively. However, final COD values
      higher than 200 mg l(-1) were obtained indicating the requirement of an
      additional treatment step. Pre-ozonation followed by coagulation/flocculation was
      not found to be an efficient treatment approach for this aim, but
      coagulation/flocculation followed by ozonation, was proved to be an efficient
      process for the reduction of COD to lower than 180 mg l(-1).

PMID- 15967480
TI  - Mineralization of Reactive Black 5 in aqueous solution by basic oxygen furnace
      slag in the presence of hydrogen peroxide.
AB  - Basic oxygen furnace slag (BOF slag) is a solid waste arisen from the steel
      making process. FeO is one of the major components of BOF slag. The FeO
      containing property of BOF slag makes it possible to catalyze the Fenton
      reaction. Reactive Black 5 (RB5) dye is chosen as the target compound in this
      study. This study has investigated the catalytic performance of BOF slag on the
      Fenton reaction to decompose RB5 in aqueous solution. A first-order kinetic model
      with respect to TOC was adopted to explain the mineralization of RB5 by the
      H(2)O(2)/BOF slag process. The experimental results in this study suggested that
      dosage with 1.49 x 10(-4)M min(-1) H(2)O(2) and 12.5 g l(-1) BOF slag in the
      solution at pH 2 provided the optimal operation conditions for the mineralization
      of RB5 yielding a 51.2% treatment efficiency at 100 min reaction time, and
      complete decoloration can be achieved within 30 min reaction time. The
      H(2)O(2)/Fe(2+) ratio was then determined to be 6.06:1.

PMID- 15967481
TI  - Steroid estrogens in ocean sediments.
AB  - This paper gives results from a study measuring the abundance of steroid hormones
      in ocean sediments in the proximity of a deep ocean sewage outfall. The outfall
      is discharge point for an enhanced primary sewage treatment plant and sediment
      samples were taken adjacent and 7 km from the outfall. All samples contained
      steroid estrogens at nanogram per gram levels with higher concentrations at the 7
      km sampling site. The concentration of estrone ranged from (0.16-1.17 ng/g),
      17beta-estradiol (0.22-2.48 ng/g) and the synthetic 17alpha-ethinylestradiol
      (<0.05-0.5 ng/g). The values detected correspond with estimates based on the
      proportion of estrogens sorbed to particles in the effluent and the expected
      proportion of particles originating from sewage in the ocean sediments. The
      results suggest that estrogens associated with the particulate fraction aggregate
      on contact with high ionic strength seawater and settle to the seafloor after
      discharge through deep ocean outfalls.

PMID- 15967482
TI  - Bioavailability of HOC depending on the colloidal state of humic substances: a
      case study with PCB-77 and Daphnia magna.
AB  - Condensed organic matter with higher affinity for hydrophobic organic compounds
      (HOC) is currently held responsible for slow desorption and concomitant lower
      bioavailabilities of HOC in sediments and soils. In an experiment with Daphnia
      magna and IHSS Peat Humic Acid (PHA), we showed that the bioconcentration factor
      (BCF) of 3,3',4,4'-tetrachlorobiphenyl (PCB-77) was directly related to the
      charge of the humic colloid, as predicted by the metal-humic binding model WHAM.
      Consistent with the type of binding to the humic acid (counter-ion accumulation
      vs. specific binding), increasing the concentration of Na+ and Ca2+ ions
      generated opposite effects on colloid charge and HOC binding by the humic acid.
      Condensation as a colloidal phenomenon in solution as well as on surfaces needs
      to be addressed as a contributor to lower bioavailabilities and, possibly, to
      slower desorption kinetics.

PMID- 15967483
TI  - Phosphorus release from ash, dried sludge and sludge residue from supercritical
      water oxidation by acid or base.
AB  - Leaching of ash and dried sewage sludge were investigated and compared with the
      leaching results of sludge residue from supercritical water oxidation (SCWO).
      This article focuses on how the composition of ash and sludge residues influences
      the extraction of phosphate and heavy metals and if different treatment
      temperatures of the sludge effect the leachability. Results showed that acid
      leaching gave a higher release of phosphate than alkaline leaching for all ash
      and sludge residue samples. Also, alkaline leaching dissolved phosphate with a
      lower metal contamination than acid leaching. Furthermore, it was found that iron
      had a low release at both alkaline and acid leaching from ash and from SCWO
      residue. The difference in composition of ash and sludge residue samples had no
      significant influence on release of phosphate at high concentrations of acid.
      Phosphate release from ash, dried sludge at 300 degrees C and SCWO residue showed
      similar results at 1M acid leaching. However, it seems to be easier to release
      phosphate from the SCWO residue than from the ash at low acid concentrations.
      SCWO residue showed higher release than the other ashes at 0.5M HCl. Results for
      alkaline leaching showed higher release from ash at 1M NaOH than from SCWO
      residue or from dried sludge at 300 degrees C. The leaching of phosphate from
      dried sludge seems to be temperature dependent, as the dried sludge treated at
      higher temperature showed less release of phosphate. It was found that the pre
      treatment of the ash may be important for better release of phosphate.

PMID- 15967484
TI  - Competitive adsorption of dye metanil yellow and RB15 in acid solutions on
      chemically cross-linked chitosan beads.
AB  - One kind of adsorbent with a high adsorption capacity for anionic dyes was
      prepared using ionically and chemically cross-linked chitosan beads. A batch
      system was applied to study the adsorption behavior of one acid dye (MY, metanil
      yellow) and one reactive dye (RB15, reactive blue 15) in aqueous solutions by the
      cross-linked chitosan beads. The adsorption capacities was 3.56 mmol g(-1) (1334
      mg g(-1)) for dye MY and 0.56 mmol g(-1) (722 mg g(-1)) for dye RB15 at pH4, 30
      degrees C. The Langmuir model agreed very well with the experimental data
      (R(2)>0.996). The kinetics of adsorption for a single dye and the kinetics of
      removal of ADMI color value in mixture solutions at different initial dye
      concentrations were evaluated by the nonlinear first-order and second-order
      models. The first-order kinetic model fits well with the dynamical adsorption
      behavior of a single dye for lower initial dye concentrations, while the second
      order kinetic model fits well for higher initial dye concentrations. The
      competitive adsorption favored the dye RB15 in the mixture solution (initial
      conc. (mM): MY=1.34; RB15=1.36); while it favored the dye MY in the mixture
      solution (initial conc. (mM): MY=3.00; RB15=1.34) and the adsorption kinetics for
      dye RB15 has the tendency to shift to a slower first order model.

PMID- 15967485
TI  - Telomere length versus hormonal and bone mineral status in healthy elderly men.
AB  - Telomeres, the termini of linear chromosomes, exert a key role in the process of
      cellular ageing. Progressive telomere shortening is implicated in senescence in
      vitro and ample evidence exists to support the hypothesis that telomere length is
      correlated with chronological age and ageing phenotypes in vivo. In this study,
      we assessed whether mean telomere length of peripheral blood leukocytes predicts
      age-associated bone loss and/or is related to sex steroid status in an elderly
      healthy male population (71-86 years). Out of this population, we selected 110
      samples for telomere restriction fragment (TRF) length analysis. Fasting blood
      was analysed for testosterone, estradiol, sex hormone binding globulin and
      biochemical markers of bone turnover. Also, the bioavailable fractions of sex
      steroids were calculated. Bone mineral density was measured at baseline and
      longitudinal follow-up was available for 84 men. We found that mean TRF length
      was inversely correlated with age (r=-0.19; P=0.049). Although no correlations
      were found with sex steroids or BMD at baseline, age corrected mean TRF length
      was associated with longitudinal bone loss for different distal forearm sites
      (P<0.05). Further studies are required to confirm our results, yet in this study,
      the predictive value of telomere length for bone loss appears to be substantial,
      hence underscoring the role of telomere length as a biomarker of ageing
      phenotypes.

PMID- 15967486
TI  - The penguin feathers as bioindicator of Antarctica environmental state.
AB  - Concentrations of biogenic and toxic elements (Na, K, Mg, Ca, P, S, Fe, Cu, Zn,
      Co, Mn, Se, Ni, Sr, Al, Cd, Pb, As) were determined for the first time in
      feathers of gentoo penguin (Pygoscelis papua) and chinstrap penguin (Pygoscelis
      antarctica) from Antarctica. A comparison of element levels was performed among
      these species in years 2002-2003. Penguins molt annually and this fact allows
      defining precisely the concentrations of accumulated toxic elements and heavy
      metals in plumage every year. A continual environmental biomonitoring could
      establish a possible trend to contamination of the Antarctica sea zones. The
      penguin feather is an excellent subject for monitoring because penguins have long
      life span, permanent ecological niche and dominate the aviafauna in Antarctica.
      Because of its remoteness, Antarctica is believed to be unpolluted. The
      relatively elevated levels of Cd established are due to the Cd-enrichment of the
      Antarctic marine food chain. Because of great bioaccumulation of lead in
      feathers, the concentration of Pb in penguin feather was higher (4-8 times)
      compared to that of Cd. In both penguin species the levels of Zn were 1.9 times
      higher than respective Fe levels. The concentrations of most of the investigated
      elements were significantly higher in P. papua than in P. antarctica and this
      probably could be explained by the different diet and feeding habit of these
      species.

PMID- 15967487
TI  - The use of a panel of monoclonal antibodies to enrich circulating breast cancer
      cells facilitates their detection.
AB  - OBJECTIVE: Metastatic relapse due to early dissemination of tumor cells is
      associated with poor prognosis for epithelial cancer. The molecular
      characterization of these single cells or cell clusters that have evaded the
      tumor is indispensable in order to evaluate their biological behavior and
      metastatic potential. In this study, we established a sensitive immunomagnetic
      method to isolate rare cancer cells from peripheral blood based on their
      expression of epithelial- or tumor-cell-specific markers. METHODS: Low numbers of
      cells of breast cancer cell lines - ZR-75-1, MCF-7, HBL-100 - were spiked into
      peripheral blood specimens of healthy volunteers. Enrichment of tumor cells was
      performed using either pre-coupled HEA and/or ErbB2 microbeads or a mixture of
      three monoclonal antibodies against HEA, ErbB2 and EGFR. RESULTS: The recovery
      rate of spiked tumor cells correlated with the expression of the corresponding
      antigens. ZR-75-1 cells high expressing all three genes could be isolated to 60
      71%. MCF-7 cells, which hardly express EGFR, showed a significant better recovery
      by using two specific antibodies in combination (50-68%) than one pre-coupled
      bead alone (31-42%). HBL-100 cells little expressing HEA could not be isolated
      with HEA microbeads and only to 27% in combination with ErbB2 beads -in contrast
      the use of an antibody cocktail achieved 38%. CONCLUSION: As tumor and epithelial
      specific cell marker antigens are expressed differently in disseminated tumor
      cells, the immunomagnetic enrichment from peripheral blood is most robust and
      reliable when using a combination of specific antibodies compared to single
      antibodies.

PMID- 15967488
TI  - Insulin-like growth factors (IGFs) in ovarian carcinoma.

PMID- 15967489
TI  - Effects of hexoses on in vitro oocyte maturation and embryo development in pigs.
AB  - The objective was to determine the effects of supplementing hexoses in oocyte
      maturation and embryo culture medium on in vitro maturation (IVM) and in vitro
      fertilization (IVF) of porcine oocytes and in vitro development of in vitro
      produced (IVP) porcine embryos. In the first experiment, oocytes were matured in
      vitro in modified North Carolina State University (NCSU)-37 medium, supplemented
      with hexoses (glucose, fructose or galactose) at various concentrations: 0
      (control), 2.5, 5.5 and 10 mM. Supplementing the maturation medium with either
      glucose or fructose (5.5 mM) increased the percentages of oocytes that matured to
      metaphase II (79.4 and 70.2%, respectively), as compared with the control group
      (P < 0.05). However, supplementing galactose had no effects on meiotic maturation
      and fertilization. In the second experiment, cleaved embryos were collected 3
      days after IVF of oocytes matured in the maturation medium supplemented with 5.5
      mM of glucose; they were cultured for an additional 4 days in modified NCSU-37
      medium, supplemented with 5.5mM of glucose, fructose or galactose. The incidence
      of blastocyst formation was higher (P < 0.05) in the glucose and fructose groups
      (18.6 and 18.2%, respectively) than in the galactose group and non-supplemented
      control group (12.9 and 9.2%). Moreover, fructose supplementation increased the
      total cell number/blastocyst (48.0 versus 37.6) and reduced the index of DNA
      fragmented nucleus in the blastocysts (7.6% versus 11.8%), as compared with
      glucose supplementation (P < 0.05). In conclusion, fructose was a practical
      alternative to glucose for supporting IVM of porcine oocytes and fructose was
      superior to glucose for producing high-quality porcine embryos in vitro.

PMID- 15967490
TI  - The effect of melatonin implants during the seasonal anestrus on embryo
      production after superovulation in aged high-prolificacy Rasa Aragonesa ewes.
AB  - The aim of this study was to assess the effect of melatonin implants administered
      in March on the ovarian cyclicity, ovulatory response and embryo production after
      repeated superovulation of selected high-prolificacy Rasa Aragonesa aged ewes.
      During the seasonal anestrus of two consecutive years, 113 superovulatory
      treatments have been performed. Ewes were treated (M) or not (C) with melatonin
      implants in March (day 0). All of them received intravaginal progestogen sponges
      on day 24 (recovery 1) and 80 (recovery 2) after melatonin implants insertion in
      year 1, and on day 28 and 77 in year 2. The intravaginal sponges were removed
      after 14 days. Superovulatory treatments consisted of eight doses in decreasing
      concentrations (2 mL x 2 and 1 mL x 6) of oFSH (Ovagen) administered twice daily
      starting 72 h before sponge removal. Seven days after the onset of estrus,
      embryos were recovered by laparotomy. Melatonin increased cyclicity only in
      recovery 2 year 2 (83% versus 42%; P < 0.05) but not in the other experimental
      periods. Among the 78% (88) ewes that ovulated and produced functional corpora
      lutea, melatonin implants tended to improve embryo viability in recovery 2 by
      increasing the number of blastocysts per superovulatory treatment (2.4 +/- 0.6
      versus 1.1 +/- 0.4; P = 0.09), the rate of viability (67 +/- 9% versus 43 +/- 9%;
      P < 0.05), and freezability (55 +/- 9% versus 33 +/- 8%; P < 0.05). More
      specifically, melatonin induced a significant reduction of the number and rate of
      non-viable (degenerate and retarded) embryos in recovery 2 (0.4+/-0.1 embryos
      versus 1.3 +/- 0.3 embryos and 4 +/- 1% versus 22 +/- 6%, respectively; P <
      0.05). Our results demonstrate that melatonin implants in March can improve at
      medium term (3 months after implantation) the viability of embryos collected from
      selected high-prolificacy Rasa Aragonesa aged ewes after superovulation.

PMID- 15967491
TI  - Frozen semen management in equine breeding programs.
AB  - Success with frozen semen requires attention to detail and a basic understanding
      of the techniques for properly handling and thawing and inseminating frozen
      semen. Practitioners should also be familiar with strategies used for managing
      mares for insemination with thawed semen. This manuscript will review those
      techniques and also present fertility data collected in a commercial setting.
      Factors that affect pregnancy rates for mares inseminated with frozen-thawed
      semen such as timing and frequency of insemination were examined for two separate
      data sets consisting of 332 and 536 mare cycles collected during the 2002 and
      2003 breeding seasons. There were no differences observed in pregnancy rates for
      mares inseminated once or multiple times in a given cycle (51.5% versus 51.7% for
      data set 1 and 47.1% versus 46.1% for data set 2). Mares inseminated twice on a
      cycle, once before and once after ovulation, became pregnant at a rate similar to
      mares inseminated once within 6h post-ovulation (48.1% versus 47.3%).

PMID- 15967493
TI  - Liquid filled nanoparticles as a drug delivery tool for protein therapeutics.
AB  - In the present study, an attempt was made to study the feasibility of
      nanoparticulate adsorbents in the presence of an absorption enhancer, as a drug
      delivery tool for the administration of erythropoietin (EPO) to the small
      intestine. Liquid filled nano- and micro-particles (LFNPS/LFMPS) were prepared
      using solid adsorbents such as porous silicon dioxide (Sylysia 550), carbon
      nanotubes (CNTs), carbon nanohorns, fullerene, charcoal and bamboo charcoal.
      Surfactants such as a saturated polyglycolysed C8-C18 glyceride (Gelucire 44/14),
      PEG-8 capryl/caprylic acid glycerides (Labrasol) and polyoxyethylene hydrogenated
      castor oil derivative (HCO-60) were used as an absorption enhancer at 50mg/kg
      along with casein/lactoferrin as enzyme inhibitors. The absorption of EPO was
      studied by measuring serum EPO levels by an ELISA method after small intestinal
      administration of EPO-LFNPS preparation to rats at the EPO dose level of 100
      IU/kg. Among the adsorbents studied, CNTs showed the highest serum EPO level of
      62.7 +/- 11.6 mIU/ml. In addition, with the use of casein, EPO absorption was
      improved, C(max) 143.1 +/- 15.2 mIU/ml. Labrasol showed the highest absorption
      enhancing effect after intra-jejunum administration than Gelucire 44/14 and HCO
      60, 25.6 +/- 3.2 and 22.2 +/- 3.6 mIU/ml, respectively. Jejunum was found to be
      the best absorption site for the absorption of EPO from LFNPS. The use of CNTs as
      LFNPS, improved the bioavailability of EPO to 11.5% following intra-small
      intestinal administration.

PMID- 15967494
TI  - Reduced platelet adhesion to titanium metal coated with apatite, albumin-apatite
      composite or laminin-apatite composite.
AB  - Titanium metal coated with apatite (HA-Ti), albumin-apatite composite (AA-Ti) or
      laminin-apatite composite (LA-Ti) was prepared by the immersion of NaOH- and heat
      treated titanium metal in a calcium phosphate solution, or one supplemented with
      albumin or laminin. Platelet adhesion to the obtained materials under flow
      conditions was investigated in real time using a cone- and plate-type viscometer
      and fluorescence labeled platelets. Adhesion and activation of the platelets on
      the HA-Ti, AA-Ti and LA-Ti were definitely suppressed as compared with those on
      untreated titanium metal with a mirror surface. Furthermore, the numbers of
      platelets adhered to AA-Ti and LA-Ti are smaller than those adhered to HA-Ti,
      although the differences were not statistically significant. These findings
      suggest that HA-Ti, AA-Ti and LA-Ti, especially AA-Ti and LA-Ti, would exhibit
      thromboresistance that is superior to commercially pure titanium metal in terms
      of platelet adhesion.

PMID- 15967495
TI  - Substrate chemistry influences the morphology and biological function of adsorbed
      extracellular matrix assemblies.
AB  - In addition to mediating cell signalling events, native extracellular matrix
      (ECM) assemblies interact with other ECM components, act as reservoirs for
      soluble signalling molecules and perform structural roles. The potential of
      native ECM assemblies in the manufacture of biomimetic materials has not been
      fully exploited due, in part, to the effects of substrate interactions on their
      morphology. We have previously demonstrated that the ECM components, fibrillin
      and type VI collagen microfibrils, exhibit substrate dependent morphologies on
      chemically and topographically variable heterogeneous surfaces. Using both
      cleaning and coating approaches on silicon wafers and glass coverslips we have
      produced chemically homogeneous, topographically similar substrates which cover a
      large amphiphilic range. Extremes of substrate amphiphilicity induced
      morphological changes in periodicity, curvature and lateral spreading which may
      mask binding sites or disrupt domain structure. Biological functionality, as
      assayed by the ability to support cell spreading, was significantly reduced for
      fibrillin microfibrils adsorbed on highly hydrophilic substrates (contact angle
      20.7 degrees) compared with less hydrophilic (contact angle 38.3 degrees) and
      hydrophobic (contact angle 92.8 degrees) substrates. With an appropriate choice
      of surface chemistry, multifunctional ECM assemblies retain their native
      morphology and biological functionality.

PMID- 15967496
TI  - Growth of embryonic renal parenchyme at the interphase of a polyester artificial
      interstitium.
AB  - The construction of an artificial kidney module by tissue engineering or the
      application of cell-based therapies for the treatment of renal failure requires
      exact information regarding the cellbiological mechanisms of parenchyme
      development in combination with different kinds of biomaterials. To learn more
      about these processes tissue cultures are frequently used experimental tools.
      However, apart from experiments with early kidney anlagen there is a lack of
      suitable in-vitro models regarding the generation and long-term maintenance of
      renal tubules. In the present paper we like to demonstrate an advanced culture
      technique, which allows to generate tubular elements derived from renal stem
      cells. For the growth of tubules it is essential to fine-tune the interface
      between the embryonic tissue and the dead fluid space within a perfusion culture
      container by offering a polyester artificial interstitium. Culture was performed
      in IMDM supplemented with hormones and growth factors but using serum-free
      conditions over 14 days. Formation of tissue was then analysed by
      immunohistochemistry and two-dimensional (2D) electrophoresis. Culture in pure
      IMDM leads to a complete loss of tissue formation. In contrast, application of
      aldosterone (A) induces the development of numerous polarised tubules.
      Surprisingly, addition of epidermal growth factor (EGF), a cocktail of insulin,
      transferrin and selenium (ITS), retinoic acid (RA), cholecalciferol (VitD3) or
      bovine pituitary extract (BPT) does not further improve development of tubules,
      but leads to intensive cell clustering and a decrease of tubule formation. 2D
      Western blots of developing tissue probed with soybean agglutinin (SBA) reveal a
      unique pattern of newly detected proteins. It is found that growth factors do not
      support but abolish protein spots upregulated by aldosterone. It remains to be
      investigated, which cellbiological effect stimulates the embryonic cells to
      develop tubules in competition to cell clusters at the interphase of an
      artificial interstitium.

PMID- 15967497
TI  - Surface engineering of stainless steel materials by covalent collagen
      immobilization to improve implant biocompatibility.
AB  - It was shown recently that the deposition of thin films of tantalum and tantalum
      oxide enhanced the long-term biocompatibility of stainless steel biomaterials due
      to an increase in their corrosion resistance. In this study, we used this
      tantalum oxide coating as a basis for covalent immobilization of a collagen
      layer, which should result in a further improvement of implant tissue
      integration. Because of the high degradation rate of natural collagen in vivo,
      covalent immobilization as well as carbodiimide induced cross-linking of the
      protein was performed. It was found that the combination of the silane-coupling
      agent aminopropyl triethoxysilane and the linker molecule N,N'
      disulphosuccinimidyl suberate was a very effective system for collagen
      immobilizing. Mechanical and enzymatic stability testing revealed a higher
      stability of covalent bound collagen layers compared to physically adsorbed
      collagen layers. The biological response induced by the surface modifications was
      evaluated by in vitro cell culture with human mesenchymal stem cells as well as
      by in vivo subcutaneous implantation into nude mice. The presence of collagen
      clearly improved the cytocompatibility of the stainless steel implants which,
      nevertheless, significantly depended on the cross-linking degree of the collagen
      layer.

PMID- 15967498
TI  - Assessing the in vitro biocompatibility of a novel carbon device for the
      treatment of sepsis.
AB  - The aim of the present study was to conduct a preliminary investigation into the
      blood biocompatibility of a novel, uncoated carbon for use in a
      filtration/adsorption device for the treatment of sepsis. Carbon well prototypes
      were manufactured from phenol-formaldehyde-aniline-based pyrolysed carbons using
      monolithic polymer technology. Inflammatory blood cell and plasma protein
      mediation of the inflammatory response were evaluated using the novel carbon
      prototypes and compared with dialyser membrane and tissue culture plate controls.
      Assays determining monocyte and granulocyte adhesion, platelet adhesion and
      activation, granulocyte activation and complement activation were performed.
      Preliminary findings suggest an adsorptive but passivating carbon surface.
      Moderate levels of monocyte and granulocytes adhesion were seen in conjunction
      with adsorption of plasma proteins to the carbon surface. Activation of
      granulocyte and adherent platelets was not detected and the complement cascade
      was not activated by the carbons, indicating a surface compatible with blood
      contact. The results support the further development of the proposed carbon-based
      device for the treatment of sepsis.

PMID- 15967499
TI  - Microtomography assessment of failure in acrylic bone cement.
AB  - Micromechanical studies of fatigue and fracture processes in acrylic bone cement
      have been limited to surface examination techniques and indirect signal analysis.
      Observations may then be mechanically unrepresentative and/or affected by the
      presence of the free surface. To overcome such limiting factors the present study
      has utilised synchrotron X-ray microtomography for the observation of internal
      defects and failure processes that occurred within a commercial bone cement
      during loading. The high resolution and the edge detection capability (via phase
      contrast imaging) have enabled clear microstructural imaging of both strongly and
      weakly absorbing features, with an effective isotropic voxel size of 0.7 microm.
      Detailed assessment of fatigue damage processes in in vitro fatigue test
      specimens is also achieved. Present observations confirm a link with macroscopic
      failure and the presence of larger voids, at which crack initiation may be linked
      to the mechanical stress concentration set up by adjacent beads at pore surfaces.
      This study does not particularly support the suggested propensity for failure to
      occur via the inter-bead matrix; however crack deflections at matrix/bead
      interfaces and the incidence of crack arrest within beads do imply locally
      increased resistance to failure and potential improvements in global crack growth
      resistance via crack tip shielding.

PMID- 15967500
TI  - Multiple effects of bioflavonoids on gene regulation, cell proliferation and
      apoptosis: natural compounds move into the lime light of cancer research.

PMID- 15967501
TI  - Rag expression identifies B and T cell lymphopoietic tissues during the
      development of common carp (Cyprinus carpio).
AB  - The generation of lymphoid cells during carp development was studied by analyzing
      expression of the recombination activating genes (rag) using in situ
      hybridization and real time quantitative PCR. These data were combined with
      immunohistochemistry using the mAb's WCL9 (cortical thymocytes) and WCI12 (B
      cells). Carp rag-1 and rag-2 showed 90 and 89% amino acid identity, respectively,
      to the corresponding zebrafish sequences. Rag-1 was first expressed in the thymus
      at 4 days post-fertilization (dpf), while both rag-1+/WCL9+ and rag-1-/WCL9-
      areas were distinguished from 1 week post-fertilization (wpf), suggesting early
      cortex/medulla differentiation. From 6 dpf, rag-1+ cells were also present cranio
      lateral of the head kidney. From 1 wpf, rag-1/rag-2 was expressed in kidney
      (together with immunoglobulin heavy chain expression) but not in spleen, while
      WCI12+ cells appeared 1 week later in both organs, suggesting B cell
      recombination in kidney but not in spleen. Rag-1 expression exceeded rag-2 levels
      in thymus and in head- and trunk-kidney of juveniles, but this ratio was reversed
      in head- and trunk-kidney from approximately 16 wpf onwards. Rag-1/rag-2
      expression was detected in thymi of animals over 1-year-old, but in kidney only
      at low levels, indicating life-long new formation of putative T cells but
      severely reduced formation of B cells in older fish.

PMID- 15967502
TI  - Electroporation-mediated transformation of Aeromonas hydrophila.
AB  - A strain of Aeromonas hydrophila producing copolyesters of 3-hydroxybutyrate and
      3-hydroxyhexanoate, abbreviated as PHBHHx, was successfully transformed by
      electroporation. The plasmid used was a broad host range plasmid pBBR1MCS.
      Electroporation conditions were varied systemically to develop an electroporation
      protocol. The optimal yield of transformant was approximately 4x10(2) CFU/microg
      DNA at 12.5 kV/cm and 1000 Omega, resulting in a time constant of approximately 5
      ms. The A. hydrophila transformants expressed plasmid-encoded resistance to
      chloromphenicol. Plasmid DNA in the A. hydrophila transformant was stably
      maintained. This is the first report of transformation of bacteria A. hydrophila.

PMID- 15967503
TI  - The relevance of irrelevance to schizophrenia.
AB  - Jeffrey Gray's neuropsychological theory of the positive symptoms of
      schizophrenia has been highly influential by enabling a strong link between
      animal and human research. Central to the development and testing of this theory
      has been the phenomenon and paradigm of latent inhibition (LI-the retardation of
      learning that one stimulus predicts the occurrence of another due to pre-exposure
      of the first stimulus). We review findings relating to its alteration in patients
      with schizophrenia (acute and chronic), people high on dimensions of schizotypy
      and the effects of amphetamine and anti-psychotic medication in humans. We
      suggest that many human-LI paradigms still suffer from theoretical and practical
      limitations, but that recent developments are beginning to address these. Finally
      we explore the idea that the paradigm of Learned Irrelevance (LIRR-the
      retardation of learning that one stimulus predicts the occurrence of another due
      to pre-exposure of both stimuli but in an unrelated manner) might be used to
      complement studies on LI in exploring the cognitive distortions suffered by
      patients with schizophrenia.

PMID- 15967504
TI  - Synthesis, characterization and biological activity of triorganotin 2-phenyl
      1,2,3-triazole-4-carboxylates.
AB  - The triorganotin 2-phenyl-1,2,3-triazole-4-carboxylates, 2-PhC2N3CO2SnR3 (R=C6H5,
      1; c-C6H11, 2; C6H5C(CH3)2CH2, 3), have been prepared and characterized by means
      of elemental analysis, IR and NMR (1H, 13C and 119Sn) spectroscopy. The crystal
      structures of 1 and 3 have been determined. Compound 1 is polymeric in nature
      with a trigonal bipyramidal configuration, and compound 3 shows a tetrahedral
      geometry. Bioassay results have shown that these compounds have good
      antibacterial and antitumor activity. The activity against three human tumor cell
      lines (HeLa, CoLo205 and MCF-7) decreased in the order 1>2>3.

PMID- 15967505
TI  - Synthesis and characterization of new copper- and zinc-chloroquine complexes and
      their activities on respiratory burst of polymorphonuclear leukocytes.
AB  - The metal-chloroquine (CQ) complexes, Cu(CQ)2Cl (1), Cu(CQ)(PPh3)(NO3) (2),
      [Cu(OAc)2(CQ)]2 (3) ZnCl2(CQ)(H2O)2 (4), [Zn(OAc)2(CQ)(H2O)]2 (5), were
      synthesized and characterized by NMR, FAB-mass, elemental analysis, and UV-Vis,
      EPR and IR spectroscopies. The effects of these compounds on the generation of
      reactive oxygen species (ROS) from human neutrophils (PMNs) were tested in the
      concentration range 1-100 microM and compared to that of chloroquine. The data
      show that the copper-chloroquine complexes 1-3 inhibit neutrophil release of ROS
      in PMNs activated either by a phorbol ester or by phagocytosable particles. Both
      effects were dose-dependent, with an IC50 of approximately 10 microM. With the
      same stimulants, there was only modest inhibition of ROS generation by any of the
      zinc-chloroquine complexes 4-5 at 10-100 microM. All complexes did not show
      significant in vitro toxicity as assayed by the trypan blue exclusion method. Our
      results reinforce previous observations that many metal derivatives of anti
      inflammatory drugs affect neutrophil functions with higher potency than their
      parent ligands.

PMID- 15967506
TI  - New method to measure water permeability in emptied-out Xenopus oocytes
      controlling conditions on both sides of the membrane.
AB  - Membrane water permeability is habitually calculated from volume changes in
      Xenopus laevis oocytes during external osmotic challenges. Nevertheless, this
      approach is limited by the uncertainty on the oocyte internal composition. To
      circumvent this limitation a new experimental set up is introduced where the cell
      membrane of an emptied-out oocyte was mounted as a diaphragm between two
      chambers. In its final configuration the oocyte membrane was part of a closed
      compartment and net water movements induced swelling or shrinking of it. Volume
      changes were followed by video-microscopy and digitally recorded. In this manner,
      water movements could be continuously monitored while controlling chemical
      composition and hydrostatic pressure on both sides of the membrane. Using this
      novel experimental approach an increasing hydrostatic pressure gradient was
      applied to both mature (stage VI) and immature (stage IV) oocytes. The relative
      maximal volume change tolerated before disruption was similar in both cases
      (1.26+/-0.07 and 1.27+/-0.03 respectively) and similar to those previously
      reported under maximal osmotic stress. Nevertheless the osmotic permeability
      coefficient (P(OSM)) in mature oocytes ((1.72+/-0.58) x 10(-3) cm s(-1); n=6) was
      significantly lower than in immature oocytes ((5.18+/-0.59) x 10(-3) cm s(-1),
      n=5; p<0.005).

PMID- 15967507
TI  - A novel fluorometric assay for ADP-ribose pyrophosphatase activity.
AB  - ADP-ribose pyrophosphatase (ADPRase) hydrolyzes ADP-ribose to ribose-5-phosphate
      and AMP. The ADPRase activity have been assessed by coupling the reaction to
      alkaline phosphatase and colorimetrically measuring the amount of inorganic
      phosphate released from AMP that is one of the products of ADPRase. Another but
      less sensitive colorimetric method has been employed: the reaction mixture was
      treated with charcoal to adsorb the adenine-containing compounds such as AMP and
      ADPR and subsequently remaining ribose-5-phosphate was measured colorimetrically.
      However, the measurement of inorganic phosphate cannot be feasible to assay
      ADPRase in phosphate-containing samples and the determination of ribose-5
      phosphate also is less sensitive. Here we develop a fluorescent assay for ADPRase
      that utilizes 1, N(6)-etheno ADP-ribose, a fluorescent analogue of ADP-ribose.
      This method measures fluorescent 1, N(6)-etheno adenosine that is produced by
      coupling the hydrolysis of 1, N(6)-etheno ADP-ribose to dephosphorylation with
      alkaline phosphatase. The fluorometric assay is comparable in sensitivity and
      useful for ADPRase assay in phosphate-containing samples.

PMID- 15967508
TI  - Automated PrPres amplification using indirect sonication.
AB  - Prions, which mainly consist of the scrapie isoform of the prion protein
      (PrP(Sc)), induce the misfolding of the physiological prion protein (PrP(C)). The
      Protein Misfolding Cyclic Amplification (PMCA), a process consisting of
      sonication and incubation, is one of the few methods thought to model
      autocatalytic prion replication and generation of proteinase K (PK)-resistant PrP
      (PrPres) in vitro. Here we show for the first time that the amplification may be
      achieved through direct as well as indirect sonication (water bath sonication
      using sealed sample containers), allowing the PMCA method to be automated. The
      automated method may serve as a valuable tool in high throughput screening for
      the diagnosis or compound identification for treatment of prion disease. The in
      vitro amplification process is weakly facilitated by divalent cations such as Mn,
      Zn and Ni, but not Cu, however, the presence of metal ions decreases the
      stability of PrPres against proteinase K digestion.

PMID- 15967509
TI  - Comparing neuronal spike trains with inhomogeneous Poisson distribution:
      evaluation procedure and experimental application in cases of cyclic activity.
AB  - A procedure is proposed to compare single-unit spiking activity elicited in
      repetitive cycles with an inhomogeneous Poisson process (IPP). Each spike
      sequence in a cycle is discretized and represented as a point process on a
      circle. The interspike interval probability density predicted for an IPP is
      computed on the basis of the experimental firing probability density; differences
      from the experimental interval distribution are assessed. This procedure was
      applied to spike trains which were repetitively induced by opening-closing
      movements of the distal article of a lobster leg. As expected, the density of
      short interspike intervals, less than 20-40 ms in length, was found to lie
      greatly below the level predicted for an IPP, reflecting the occurrence of the
      refractory period. Conversely, longer intervals, ranging from 20-40 to 100-120
      ms, were markedly more abundant than expected; this provided evidence for a time
      window of increased tendency to fire again after a spike. Less consistently, a
      weak depression of spike generation was observed for longer intervals. A Monte
      Carlo procedure, implemented for comparison, produced quite similar results, but
      was slightly less precise and more demanding as concerns computation time.

PMID- 15967510
TI  - Reliability assessment of an automated forced swim test device using two mouse
      strains.
AB  - The Porsolt forced swim test (FST) is one of the most widely used behavioral
      tests in the evaluation of the antidepressant effects of drugs. It is based on
      the fact that these drugs reduce the depression-related behaviors of learned
      helplessness. The model has been modified for use in mice. In contrast to rats,
      mice are exposed to forced swimming only once and their immobility behavior is
      measured and considered a "depression-like" phenotype. Like many other behavioral
      tests, FST can be affected by observer-related artifacts. In recent years,
      automated testing systems have been developed to decrease artifacts that may
      greatly influence the interpretation of results. In this work, we used two
      strains of mice, i.e., C3H/HeJ and C57BL/6J, which differ in their FST immobility
      times. We employed a new commercially available automated FST device and a
      blinded observer-based FST, and we examined their ability to measure behavioral
      differences between these two mouse strains. Our results suggest that the tested
      automated FST system generates reliable data comparable to results obtained by
      trained observers.

PMID- 15967511
TI  - Partial sleep deprivation therapy combined with sertraline induces more rapid
      improvements in quality of life items in major depressive disorder.
AB  - BACKGROUND: Total or partial sleep deprivation was showed to have rapid
      antidepressive effects in depression. Sleep deprivation therapy in major
      depression constitutes insufficient antidepressive treatment response and
      depressive symptoms reoccur after one night of recovery. Combination of
      antidepressant medication with sleep deprivation therapy is generally indicated.
      These combination therapies were found more favorable overall therapeutic effect
      than antidepressive monotherapy. METHODS: In this study, we examined the Quality
      of Life changes with the antidepressive therapy using partial sleep deprivation
      plus sertraline and sertraline monotherapy in patients with major depressive
      disorder. Thirteen patients received six partial sleep deprivation therapies in
      addition to sertraline, that sleep schedule in deprivation nights started at
      11:00-12:00 p.m. to 03:00 a.m. and 11 patients treated with sertraline
      monotherapy as a control group. Quality of Life was evaluated with the WHOQOL
      100, depression and the accompanying anxiety were also assessed at baseline and
      at the end of the 4th week. RESULTS: Patients treated with combination therapy
      improved significantly and more rapidly. Rapid improvement in quality of life in
      major depressive disorder was showed in patients treated with combination of late
      partial sleep deprivation and sertraline. LIMITATIONS: Small sample size, the
      lack of placebo group and short duration of the study are the main limitations.
      CONCLUSIONS: In clinical practice, QOL improvement can be accelerated using
      combination of partial sleep deprivation with the sertraline therapy.

PMID- 15967512
TI  - Characterisation of the immunoglobulin variable region gene usage encoding the
      murine anti-ganglioside antibody repertoire.
AB  - Neuropathogenic murine antibodies reactive with terminal disialylgalactose
      epitopes are innate and preferentially encoded by the VH7183.3b gene. Here we
      have studied antibodies reactive with internal galactose-linked disialosyl
      epitopes and the terminal trisaccharide of GT1b. Antibodies were of moderate
      affinity and unmutated. Anti-GD1b antibodies were often encoded by the VH10.2b
      heavy and gj38c light chain genes. Anti-GT1b antibodies with broader glycan
      binding patterns were encoded by VHQ52 and VHJ558 family genes. These data
      indicate that the discrete specificities of ganglioside-binding antibodies are
      dictated by particular patterns of V gene usage residing within the innate B cell
      repertoire.

PMID- 15967513
TI  - Development of broadly targeted human endogenous gammaretroviral pol-based real
      time PCRs Quantitation of RNA expression in human tissues.
AB  - Endogenous retroviral sequences (ERVs) are dynamic genomic components with
      profound influences on gene expression and genomic structure. Their extent of
      expression is not well known. Several broadly targeted real-time reverse
      transcription PCR (QPCRs) systems for surveillance of RNA expression of the major
      groups of human gammaretroviral ERVs were constructed. The highly conserved
      reverse transcriptase (RT) and integrase (IN) domains of the pol gene were used
      as targets for the PCRs, which were both probe-based (TaqMan) and probe-less
      (SYBR Green). Different levels of primer and probe degeneracy, with or without
      inosine, were tested. Several of the PCRs had sensitivities of a few HERV nucleic
      acid copies per PCR reaction. Specificities were approximately as expected from
      the fit of primers and probes. Gammaretroviral HERV RNA expression was studied in
      different human tissues. Each HERV group had a specific pattern of expression.
      HERV-E was highly expressed in testis, HERV-I/T in brain and testis, HERV-H in
      brain and testis, while HERV-W was highly expressed in placenta. Gammaretroviral
      RNA was not detected in plasma from 50 blood donors in saliva from 20 persons. In
      conclusion, a set of tools for investigation of gammaretroviral HERV RNA
      expression was created.

PMID- 15967514
TI  - The effect of REM sleep deprivation on motivation for food reward.
AB  - Prolonged sleep deprivation in rats produces a characteristic syndrome consisting
      of an increase in food intake yet a decrease in weight. Moreover, the increase in
      food intake generally precedes the weight loss, suggesting that sleep deprivation
      may affect appetitive behaviors. Using the multiple platform method to produce
      rapid eye movement (REM) sleep deprivation, we investigated the effect of REM
      sleep deprivation (REMSD) on motivation for food reward utilizing food-reinforced
      operant tasks. In acquisition or maintenance of an operant task, REM sleep
      deprived rats, with or without simultaneous food restriction, decreased
      responding for sucrose pellet reward in comparison to controls, despite the fact
      that all REM sleep-deprived rats lost weight. Furthermore, the overall response
      deficit of the REM sleep-deprived rats was due to a within-session decline in
      responding. REM sleep-deprived rats showed evidence of understanding the
      contingency of the task comparable to controls throughout deprivation period,
      suggesting that the decrements in responding were not primarily related to
      deficits in learning or memory. Rather, REM sleep deprivation appears to alter
      systems involved in motivational processes, reward, and/or attention.

PMID- 15967515
TI  - Bioaccumulation and the effects of organochlorine pesticides, PAH and heavy
      metals in the Eel (Anguilla anguilla) at the Camargue Nature Reserve, France.
AB  - Pesticides (organochlorines-OC), polycyclic aromatic hydrocarbons (PAH) and heavy
      metals are toxic to fish and may be taken in through gills, skin and contaminated
      foods. Here we measure concentrations of OC, PAH and heavy metals, and their
      effects in the eel Anguilla anguilla from three locations in the Camargue Reserve
      in southern France. The Camargue Biosphere Reserve is the largest coastal wetland
      in Western Europe, and A. anguilla is a common predator at the top of the food
      chain. Livers and spleens were analyzed for histopathological, chemical and
      organo-somatic (HSI and SSI) effects. Gill, liver and spleen samples were
      collected for histopathological studies. Livers and muscles were sampled for
      metabolic parameters and persistent organic pollutant analysis. Total lipids were
      estimated by spectrophotometry and lipid-free residues were used in protein and
      glycogen analysis. OC pesticides were extracted from lipids of muscles and
      livers, analyzed by gas chromatography, and PAH from bile were analyzed by fixed
      wavelength fluorescence spectrofluorimetry. Heavy metals were measured by
      inductively coupled plasma with optical or with mass spectrometers. High
      concentrations of contaminants were found in eel tissues. La Capeliere had the
      greatest OC and PAH concentrations; unexpected lesions in gills, livers and
      spleens were more common at the other sites. Liver and spleen tumors and
      lipidosis in livers were associated with chronic, and gill lesions with acute
      exposure. High pesticide and PAH concentrations and lesions in eels from the
      Camargue reserve demonstrate the contamination of the area. A more complete study
      in the Camargue reserve is necessary to better understand the impact on wildlife
      and humans. Also, this study suggests that eel biology must be better understood
      before continued use of this species as a biomonitor of polluted areas.

PMID- 15967516
TI  - Angiotensin II AT1 receptor mutants expressed in CHO cells caused morphological
      change and inhibition of cell growth.
AB  - To assess the importance of the leucine residues in positions 262 and 265 of the
      angiotensin AT(1) receptor for signaling pathways and receptor expression and
      regulation, we compared the properties of CHO cells transfected with the wild
      type or the L262D or L265D receptor point mutants. It was found that the two
      mutants significantly increased the basal intracellular cyclic AMP (cAMP)
      formation in an agonist-independent mode. The morphology transformation of CHO
      cells was correlated with the increased cAMP formation, since forskolin, a direct
      activator of adenylate cyclase mimicked this effect on WT-expressing CHO cells.
      DNA synthesis was found to be inhibited in these cell lines, indicating that cAMP
      may also have determined the inhibitory effect on cell growth, in addition to the
      cell transformation from a tumorigenic to a non-tumorigenic phenotype. However a
      role for an increased Ca2+ influx induced by the mutants in non-stimulated cells
      cannot be ruled out since this ion also was shown to cause transformed cells to
      regain the morphology and growth regulation.

PMID- 15967517
TI  - Accumulation and nuclear import of HIF1 alpha during high and low oxygen
      concentration in skeletal muscle cells in primary culture.
AB  - The hypoxia-inducible-factor-1 (HIF1) mediates the transcriptional upregulation
      of several target genes during hypoxia. HIF1 itself is known to be regulated
      essentially by ubiquitinylation and proteolytic degradation of the subunit
      HIF1alpha of the dimeric transcription factor HIF1. In contrast to other tissues,
      skeletal muscle expresses high amounts of HIF1alpha in normoxia as well as in
      hypoxia. In view of this, we aimed to investigate HIF1alpha accumulation and
      subcellular localization as well as the transcriptional activity of the HIF1alpha
      regulated gene of glyceraldehyde dehydrogenase (GAPDH) in skeletal muscle cells
      exposed to low oxygen concentration (3% O2), normoxia (20% O2) or high oxygen
      concentration (42% O2). Immunofluorescence analysis reveals that under normoxic
      and high oxygen conditions, significant amounts of HIF1alpha can be found
      exclusively in the cytoplasm of the myotubes. Muscle cells treated with CoCl2, a
      known inhibitor of HIF1alpha degradation, show even higher levels of HIF1alpha,
      again exclusively in the cytoplasm. Under conditions of low oxygen, HIF1alpha in
      controls as well as in CoCl2-treated cells is found in the nuclei. CdCl2 inhibits
      nuclear import of HIF1alpha at low oxygen concentration and leads to a
      transcriptional downregulation of the marker enzyme of anaerobic glycolysis
      GAPDH. Immunoprecipitation with anti-HIF1alpha antibody co-precipitates HSP90 in
      an oxygen-dependent manner, more at high pO2 than at low pO2. Cadmium-treated
      samples also show high amounts of co-immunoprecipitated HSP90, independent of
      oxygen concentration. We conclude that in skeletal muscle cells, HIF1alpha, in
      contrast to other tissues, may, in addition to its regulation by degradation,
      also be regulated by binding to HSP90 and subsequent inhibition of its import
      into the nuclei.

PMID- 15967518
TI  - Autonomic dysfunction in left ventricular hypertrabeculation/noncompaction.
AB  - The findings of Kawasaki et al. [T. Kawasaki, A. Azuma, T. Taniguchi, et al.
      Heart rate variability in adult patients with isolated left ventricular
      noncompaction. Int J Cardiol 2005;99:147-150.] raise the following questions: why
      was dilated cardiomyopathy not investigated? How many of the patients with left
      ventricular hypertrabeculation/noncompaction (LVHT) showed abnormalities in the
      resting ECG and in the 24-h-Holter-monitoring? Was there any correlation with
      extension of LVHT and heart rate variability? Were the patients investigated
      neurologically and did they show other signs of autonomic dysfunction? To assess
      vegetative activity in LVHT patients, more comprehensive testing than simply
      Holter-monitoring is required.

PMID- 15967519
TI  - Intracoronary aspiration for bailout management of the no-reflow during
      percutaneous coronary intervention.
AB  - The no-reflow phenomenon is frequently associated with adverse outcomes in
      patients undergoing percutaneous coronary intervention (PCI). We describe two
      cases in which the no-reflow phenomenon developed during PCI and was successfully
      resolved by direct intracoronary aspiration using the Export aspiration catheter.

PMID- 15967521
TI  - Heterologous protein expression in filamentous fungi.
AB  - Filamentous fungi are commonly used in the fermentation industry for the large
      scale production of proteins--mainly industrial enzymes. Recent advances in
      fungal genomics and related experimental technologies such as gene arrays and
      proteomics are rapidly changing the approaches to the development and use of
      filamentous fungi as hosts for the production of both homologous and heterologous
      gene products. The emphasis is moving towards sourcing new genes of interest
      through database mining and unravelling the circuits related to fungal gene
      regulation, applying, for example, transcriptomics. However, although
      heterologous fungal proteins are efficiently expressed, expression of gene
      products from other organisms is subject to several bottlenecks that reduce
      yield. Current approaches emphasize the study of pathways involved in protein
      modification and degradation in general rather than gene-by-gene approaches.

PMID- 15967522
TI  - Will nanotechnology make the world a better place?
AB  - Nanotechnology could produce a revolutionary wave of innovation in society. The
      form that such a revolution might take will depend upon many things but certainly
      upon the context, content and purposes of research projects and agendas decided
      by existing political and corporate institutions. Lessons from the genetically
      modified organism debate indicate that the behaviour of these institutions is at
      least as important as the 'risk' in informing public acceptability. This article
      argues that current research priorities need to shift in favour of environmental
      and health protection to engender public support and/or an ongoing need to remain
      sensitive to emerging societal preferences.

PMID- 15967523
TI  - The future of fluorescence sensor arrays.
AB  - The rapid progress in sensor and biosensor array technologies needs a general
      strategy in the design of fluorescence reporters. Such reporters should provide a
      high density of sensor elements, allow analysis of targets of different
      affinities, and be internally calibrated, reproducible and have a rapid readout.
      Several criteria are introduced here for the comparative evaluation of
      fluorescence-sensing techniques. It is shown that only the two-band wavelength
      ratiometric sensing with a single reporter dye exhibiting rapid reversible
      excited-state reaction can satisfy all these criteria and is a prospective
      candidate for further development.

PMID- 15967524
TI  - The magnetic resonance detected intraprostatic lesion in prostate cancer:
      planning and delivery of intensity-modulated radiotherapy.
AB  - BACKGROUND AND PURPOSE: Local relapse after radiotherapy for prostate cancer
      mostly originates at the original tumor location. Dose escalation reduces local
      relapse rates. It may be of benefit to focus the highest dose to the
      intraprostatic lesion (GTVMRI) using intensity-modulated radiotherapy (IMRT).
      Therefore, the visualization of the GTVMRI and its inclusion into computer
      optimization is mandatory. MATERIALS AND METHODS: Fifteen patients with prostatic
      adenocarcinoma were referred for IMRT. All these patients had a palpable lesion
      on digital rectal examination (DRE) and/or a PSA >10.0 ng/ml. A T2-weighted MR
      examination of the prostate was performed in order to detect a GTV(MRI) and
      correlate the location of the GTV(MRI) with the site of the tumour-containing
      cylinder (biopsy). Two IMRT plans were compared: a plan without the inclusion of
      the GTV(MRI) (IMRT-CONV) versus a plan including the GTV(MRI) into the plan
      optimization (IMRT-GTV(MRI)). For comparison, both physical and biological
      endpoints of the GTV(MRI), CTV, PTV and rectum were taken into account. After the
      finalization of the planning study, the IMRT-GTV(MRI) plans were clinically
      delivered using step-and-shoot IMRT. Acute gastro-intestinal (GI) and genito
      urinary (GU) toxicity were recorded. RESULTS: In all cases, the location of the
      GTV(MRI) corresponded with the site of the tumor containing biopsy cylinder. The
      mean and median distance of the GTV(MRI) to the anterior rectal wall was 3 and
      2mm, respectively (range: 0-12 mm). For the GTV(MRI), its inclusion in the
      optimization led to a significant increase of all physical endpoints (P<0.01),
      without compromising the dose to the CTV, PTV and rectum. Mean GTV(MRI) dose was
      78.3 Gy (IMRT-GTV(MRI)) versus 76.9 Gy (IMRT-CONV) (P<0.00001). All IMRT
      treatments were successfully delivered within 6 min. We did not observe grade 3
      acute GI toxicity. One patient developed grade 3 GU toxicity (nocturia), that
      disappeared after administration of medication. Grade 2 GI and GU toxicity was
      observed in, respectively, four and six patients. CONCLUSION: Using T2-weighted
      MR, the visualization of an intraprostatic lesion is feasible. The inclusion of
      the GTV(MRI) into planning optimization leads to a modest increase in dose,
      without compromising the dose to the CTV, PTV and organs at risk. The clinical
      delivery of these plans runs without problems. Acute toxicity is mild.

PMID- 15967525
TI  - Micro ionization chamber dosimetry in IMRT verification: clinical implications of
      dosimetric errors in the PTV.
AB  - BACKGROUND AND PURPOSE: Absolute dose measurements for Intensity Modulated
      Radiotherapy (IMRT) beamlets is difficult due to the lack of lateral electron
      equilibrium. Recently we found that the absolute dosimetry in the penumbra region
      of the IMRT beamlet, can suffer from significant errors (Capote et al., Med Phys
      31 (2004) 2416-2422). This work has the goal to estimate the error made when
      measuring the Planning Target Volume's (PTV) absolute dose by a micro ion chamber
      (microIC) in typical IMRT treatment. The dose error comes from the assumption
      that the dosimetric parameters determining the absolute dose are the same as for
      the reference conditions. MATERIALS AND METHODS: Two IMRT treatment plans for
      common prostate carcinoma case, derived by forward and inverse optimisation, were
      considered. Detailed geometrical simulation of the microIC and the dose
      verification set-up was performed. The Monte Carlo (MC) simulation allows us to
      calculate the delivered dose to water and the dose delivered to the active volume
      of the ion chamber. However, the measured dose in water is usually derived from
      chamber readings assuming reference conditions. The MC simulation provides needed
      correction factors for ion chamber dosimetry in non reference conditions.
      RESULTS: Dose calculations were carried out for some representative beamlets, a
      combination of segments and for the delivered IMRT treatments. We observe that
      the largest dose errors (i.e. the largest correction factors) correspond to the
      smaller contribution of the corresponding IMRT beamlets to the total dose
      delivered in the ionization chamber within PTV. CONCLUSION: The clinical impact
      of the calculated dose error in PTV measured dose was found to be negligible for
      studied IMRT treatments.

PMID- 15967527
TI  - Brain oscillatory responses to an auditory-verbal working memory task in mild
      cognitive impairment and Alzheimer's disease.
AB  - We report preliminary findings on EEG oscillatory correlates of working memory in
      mild cognitive impairment (MCI) and Alzheimer's disease (AD). Event-related
      desynchronization (ERD) and synchronization (ERS) of the 1-20 Hz EEG frequencies
      were studied using wavelet transforms in elderly controls, MCI patients and mild
      probable AD patients performing an auditory-verbal Sternberg memory task.
      Behaviourally, the AD patients made more errors than the controls and the MCI
      group. Statistically significant differences during the encoding of the memory
      set were found between the controls and the MCI group, such that the latter group
      showed ERD in the approximately 10-20 Hz frequencies. The findings may reflect
      different, compensatory encoding strategies in MCI. During retrieval, the most
      obvious differences were observed between the controls and the AD group: the ERD
      in the approximately 7-17 Hz frequencies was absent in the AD group particularly
      in anterior and left temporal electrode locations. This finding might indicate
      that AD is associated with deficient lexical-semantic processing during the
      retrieval phase in working memory tasks. Future studies with larger patient
      groups are needed to establish the diagnostic value of ERD/ERS patterns in MCI
      and AD.

PMID- 15967528
TI  - Fronto-parietal EEG coherence in theta and upper alpha reflect central executive
      functions of working memory.
AB  - For human working memory the neural correlates of the phonological loop and the
      visuospatial sketch pad are well explored. In contrast, less is known about
      central executive processes. Neuroimaging studies suggest that central executive
      processes are related to a complex fronto-parietal network. In the present study
      we investigate the question whether varying demands on central executive
      processes are reflected by differences in coherent activity between and within a
      fronto-parietal network. We calculated coherence during a visuospatial working
      memory task. Under an easy executive condition subjects had to mentally imagine
      previously studied abstract patterns, whereas in the difficult condition,
      subjects had to mentally manipulate these patterns. The results indicate the
      involvement of prefrontal areas in executive functions reflected by a decrease of
      anterior upper alpha short-range connectivity and a parallel increase of fronto
      parietal long-range coherence mirroring activation of a fronto-parietal network.

PMID- 15967529
TI  - Reduced gamma-band coherence to distorted feedback during speech when what you
      say is not what you hear.
AB  - BACKGROUND: Communication between the frontal lobes, where speech is generated,
      and the temporal lobes, where it is perceived, may occur through the action of an
      efference copy/corollary discharge mechanism that prepares the temporal lobes for
      the expected sound. We suggest that coherence of EEG in gamma-band between
      frontal and temporal lobes may reflect the successful action of such a mechanism.
      We tested the hypothesis that there would be a disruption of gamma-band coherence
      when the expected auditory consequence of speech does not match the auditory
      experience. METHOD: EEG was recorded from 21 healthy adult subjects as they
      uttered the sound [a:] (Talking condition) and as they heard these recorded
      sounds played back (Listening condition). As they spoke, subjects heard real-time
      feedback of the sounds that were: (1) pitch-shifted down one semi-tone, (2) pitch
      shifted down one-half of a semi-tone, or (3) not pitch-shifted (veridical), each
      in separate runs. Event-related gamma coherence between frontal and temporal
      sites was calculated relative to the onset of the sound, as it was being spoken
      during Talking, and as it was being played back during Listening. RESULTS:
      Frontal-temporal gamma-band coherence spanning 33-43 Hz was greater during
      Talking than Listening and greater when speech was veridical than when it was
      distorted a whole semi-tone. CONCLUSIONS: Gamma-band fronto-temporal synchrony
      may reflect a "binding of expectation with experience." Disruption of this
      synchrony may provide feedback to the frontal lobes, particularly regions
      subserving vocalization, to implement sensorimotor adaptations to either adjust
      motor programs for speech production in the short run, or to reorganize
      expectations in the long run.

PMID- 15967530
TI  - Multiple norovirus genotypes characterised from an oyster-associated outbreak of
      gastroenteritis.
AB  - The diversity of norovirus (NV) genotypes was investigated in persons who were
      ill with acute gastroenteritis associated with the consumption of oysters.
      Initial results from a commercial enzyme immunoassay (EIA) indicated a mixed NV
      genogroup I (GI) and II (GII) outbreak. A reverse-transcriptase (RT)-PCR for NVs
      was applied to nucleic acid extracted from faecal specimens collected from
      symptomatic cases. Using primers that amplified contiguous sequences in the
      ORF1/2 region of the NV genome and a hemi-nested PCR derived from this assay,
      three different GII and two GI NV genotypes were detected and the strains were
      characterised by DNA sequencing. Using this approach a recombinant NV genotype,
      rGII-3a (recombinant Harrow/Mexico) the predominant strain identified in several
      symptomatic cases from the outbreak, was detected and characterised. No other
      gastroenteric viruses, including rotavirus, astrovirus, sapovirus and adenovirus
      40/41 were detected by RT-PCR and PCR.

PMID- 15967531
TI  - PCR detection assays for the ochratoxin-producing Aspergillus carbonarius and
      Aspergillus ochraceus species.
AB  - Two PCR assays have been developed to detect Aspergillus carbonarius and
      Aspergillus ochraceus, considered the main sources of ochratoxin A (OTA)
      contaminating commodities, particularly grapes, coffee and derivatives, in warm
      climates. The species specific primers have been designed on the basis of ITS
      (internal transcribed spacers of rDNA units) sequence comparisons obtained from
      Aspergillus strains and have been tested in a number of strains from different
      origins and hosts. These PCR assays, based on multi-copy sequences, are highly
      sensitive and specific and represent a good tool for an early detection of OTA
      producing Aspergillus species and to prevent OTA entering the food chain.

PMID- 15967532
TI  - Lon and ClpP proteases participate in the physiological disintegration of
      bacterial inclusion bodies.
AB  - Aggregated protein is solubilized by the combined activity of chaperones ClpB,
      DnaK and small heat-shock proteins, and this could account, at least partially,
      for the physiological disintegration of bacterial inclusion bodies. In vivo, the
      involvement of proteases in this process had been suspected but not investigated.
      By using an aggregation prone beta-galactosidase fusion protein produced in
      Escherichia coli, we show in this study that the main ATP-dependent proteases Lon
      and ClpP participate in the physiological disintegration of cytoplasmic inclusion
      bodies, their absence minimizing the protein removal up to 40%. However, the role
      of these proteases is clearly distinguishable especially regarding the fate of
      solubilized protein. While Lon appears as a minor contributor in the
      disintegration process, ClpP directs an important attack on the released or
      releasable protein even not being irreversibly misfolded. ClpP is then observed
      as a wide-spectrum, main processor of aggregation-prone proteins and also of
      polypeptides physiologically released from inclusion bodies, even when occurring
      as soluble versions with a conformation compatible with their enzymatic activity.

PMID- 15967533
TI  - Transfection efficiency of chitosan vectors: effect of polymer molecular weight
      and degree of deacetylation.
AB  - Chitosans of defined molecular weight (Mw 10-213 kDa) and degree of deacetylation
      (DD 46-88%) were synthesized, complexed with pEGFP-C2 plasmid into nanoparticles
      (NP) and evaluated for cellular uptake and transfection efficiency in the A549
      cell model. DNA condensation of >90% was achieved at the N/P ratio of 6,
      independent of the chitosan Mw and DD. However, chitosan vectors of lower Mw or
      DD were less efficient at retaining the DNA upon dilution, and consequentially,
      less capable of protecting the condensed DNA from degradation by DNase and serum
      components. A549 cellular uptake of the NP was also significantly reduced by
      decreasing the Mw or DD of the chitosan vector. These factors contributed to the
      low transfection efficiencies for chitosan vectors of low Mw or DD. There was
      good correlation between transfection efficiency, cellular uptake and zeta
      potential of the NP, suggesting that cellular uptake mediated by electrostatic
      interactions with the cell membrane preceded efficient transfection. NP produced
      with chitosan of Mw 213 kDa and DD of 88% showed the highest zeta potential (+23
      mV), cellular uptake (4.1 microg/mg protein) and transfection efficiency (12.1%),
      while chitosan vector with Mw of 213 kDa and DD of 46% showed the lowest cellular
      uptake (0.4 microg/mg protein) and transfection efficiency (0.05%). Confocal
      microscopy images suggested that the chitosan-complexed DNA successfully escaped
      from the endo-lysosomal compartment for nuclear translocation and expression.
      Intracellular DNA disassembly appeared to occur at different locations depending
      on the retentive capacity of the chitosan vector.

PMID- 15967534
TI  - Ultrasound-enhanced transfection activity of HPMA-stabilized DNA polyplexes with
      prolonged plasma circulation.
AB  - Cancer gene therapy would greatly benefit from the possibility to deliver
      therapeutic genes via tumor-targeted systemic intravenous delivery. The main
      objective of this study was to determine biophysical, transfection, and
      pharmacokinetic properties of DNA complexes with reducible polycations that are
      reversibly stabilized by surface coating with multivalent HPMA copolymers. The
      specific goals were to evaluate compatibility of these polyplexes with extended
      plasma circulation, molecular targeting, and ultrasound-enhanced transfection
      activity. It was demonstrated that using polyplexes based on reducible
      polycations allows increasing transfection activity and preserving extended
      plasma circulation half-life observed for control polyplexes based on non
      reducible polycations. In addition, the reversibly stabilized polyplexes were
      compatible with both molecular targeting using protein ligands as well as
      physical targeting using ultrasound-directed cavitation in vitro. As such, the
      described gene delivery vectors have the potential to permit efficient systemic
      delivery of therapeutic genes targeted by a local focused ultrasound treatment.

PMID- 15967535
TI  - Lipid cubic phases for improved topical drug delivery in photodynamic therapy.
AB  - We have evaluated the efficacy of lipid cubic phases, highly ordered self
      assembly systems on the nanometer level, as drug delivery vehicles for in vivo
      topical administration of delta-aminolevulinic acid (ALA) and its methyl ester (m
      ALA) on nude mice skin. ALA, a precursor of heme, induces the production of the
      photosensitizer protoporphyrin IX (PpIX) in living tissue. Measuring the PpIX
      fluorescence at the skin surface, after topical administration, makes indirect
      quantification of the penetration of ALA into the tissue possible. Cubic phases
      were formed of lipid (monoolein or phytantriol), water and drug. In some cases,
      propylene glycol was included in the cubic phase as well. The drug concentration
      was 3% (w/w, based on the total sample weight) in all investigated vehicles. When
      the formulations were applied for 1 h, the monoolein cubic systems and the three
      component phytantriol sample showed higher fluorescence compared to the standard
      ointment during the 10 h of measurement. Both ALA and m-ALA yielded similar
      results, although the differences between the investigated vehicles were more
      pronounced when using m-ALA. For the 24-h applications, the monoolein cubic
      systems with m-ALA showed faster PpIX formation than the standard ointment,
      implying higher PpIX levels at short application times (less than 4 h). The
      systemic PpIX fluorescence of ALA was elevated by using the lipid cubic
      formulations. Notably, a small systemic effect was also observed for the
      monoolein cubic sample with m-ALA. These results imply improved PpIX formation
      when using the lipid cubic systems, most probably due to enhanced drug
      penetration.

PMID- 15967536
TI  - Using different structure types of microemulsions for the preparation of
      poly(alkylcyanoacrylate) nanoparticles by interfacial polymerization.
AB  - A phase diagram of the pseudoternary system ethyloleate, polyoxyethylene 20
      sorbitan mono-oleate/sorbitan monolaurate and water with butanol as a
      cosurfactant was prepared. Areas containing optically isotropic, low viscosity
      one-phase systems were identified and systems therein designated as w/o droplet-,
      bicontinuous- or solution-type microemulsions using conductivity, viscosity, cryo
      field emission scanning electron microscopy and self-diffusion NMR. Nanoparticles
      were prepared by interfacial polymerization of selected w/o droplet, bicontinuous
      or solution-type microemulsions with ethyl-2-cyanoacrylate. Morphology of the
      particles and entrapment of the water-soluble model protein ovalbumin were
      investigated. Addition of monomer to the different types of microemulsions (w/o
      droplet, bicontinuous, solution) led to the formation of nanoparticles, which
      were similar in size ( approximately 250 nm), polydispersity index (
      approximately 0.13), zeta-potential ( approximately -17 mV) and morphology. The
      entrapment of the protein within these particles was up to 95%, depending on the
      amount of monomer used for polymerization and the type of microemulsion used as a
      polymerization template. The formation of particles with similar characteristics
      from templates having different microstructure is surprising, particularly
      considering that polymerization is expected to occur at the water-oil interface
      by base-catalysed polymerization. Dynamics within the template (stirring,
      viscosity) or indeed interfacial phenomena relating to the solid-liquid interface
      appear to be more important for the determination of nanoparticle morphology and
      characteristics than the microstructure of the template system.

PMID- 15967537
TI  - Hox clusters as models for vertebrate genome evolution.
AB  - The surprising variation in the number of Hox clusters and the genomic
      architecture within vertebrate lineages, especially within the ray-finned fish,
      reflects a history of duplications and subsequent lineage-specific gene loss.
      Recent research on the evolution of conserved non-coding sequences (CNS) in Hox
      clusters promises to reveal interesting results for functional and phenotypic
      diversification.

PMID- 15967538
TI  - Cholesterol biosynthesis and the pro-apoptotic effects of the p75 nerve growth
      factor receptor in PC12 pheochromocytoma cells.
AB  - Neocarzinostatin (NCS), an enediyne antimitotic agent, induces cell death in both
      p75NTR neurotrophin receptor (NTR)-positive and p75NTR-negative PC12 cells in a
      concentration-dependent fashion. However, p75NTR-positive cells demonstrate a
      higher susceptibility to NCS-induced cell damage. Furthermore, treatment of
      p75NTR-positive cells with the p75NTR-specific ligand, MC192, resulted in
      apoptosis, while treatment of these cells with the TrkA-specific ligand, NGF
      mAbNGF30, protected them from NCS-induced death, implying that both the naked and
      liganded p75NTR receptors have a pro-apoptotic effect on PC12 cells. Microarray
      studies aimed at examining differential gene expression between p75NTR-positive
      and p75NTR-negative cells suggested that enzymes of the cholesterol biosynthetic
      pathway are differentially expressed. We therefore tested the hypothesis that
      altered cholesterol biosynthesis contributes directly to the pro-apoptotic
      effects of p75NTR in this PC12 cell-NCS model. Subsequent Northern blotting
      studies confirmed that the expression of p75NTR is associated with the
      upregulation of cholesterol biosynthetic enzymes including 3-hydroxy-3
      methylglutaryl CoA reductase (HMG CoA reductase), farnesyl-diphosphate synthase,
      and 7-dehydro-cholesterol reductase. Mevastatin, an HMG CoA reductase inhibitor,
      converts the apoptosis susceptibility of p75NTR-positive cells to that of p75NTR
      negative cells. It does so at concentrations that do not themselves alter cell
      survival. These studies provide evidence that the pro-apoptotic effects of p75NTR
      in PC12 cells are related to the upregulation of cholesterol biosynthetic enzymes
      and consequent increased cholesterol biosynthesis.

PMID- 15967539
TI  - Polymorphism of the untranslated regions of the F3/contactin mRNA in the rat
      nervous system.
AB  - F3/contactin is a neural adhesion molecule implicated in various physiological
      processes. In rat brain tissues, we cloned various mRNA with the same coding
      region but differing in 3' and 5'UTR. The 3'UTR presents two polyadenylation
      signals. At the 5' end, we identified two leader exons, multiple transcription
      initiation sites and splicing events, leading to at least 19 different 5'UTR. The
      F3/contactin rat gene differs from the mouse gene for two reasons: (1) it
      contains two additional untranslated exons that are alternatively spliced and (2)
      it lacks the homologue mouse untranslated exon 0.

PMID- 15967541
TI  - Is postoperative chemotherapy and/or postoperative radiotherapy in stage IIIA non
      small cell lung cancer feasible?

PMID- 15967542
TI  - The night eating syndrome: a progress report.
AB  - The night eating syndrome (NES) is an eating disorder marked by a delay in the
      circadian pattern of eating that disrupts sleep. Studies have shown that those
      with NES eat a significant proportion of their calories after their evening meal
      and wake up during the night to eat. However, the timing of the sleep cycles are
      phase appropriate, with similar bedtimes and morning wake up times as control
      subjects, suggesting that the delayed eating rhythm may secondarily disrupt
      sleep. A case study and an open-label trial with SSRIs suggest that they may
      treat NES effectively. Randomized controlled trials are needed.

PMID- 15967543
TI  - An innovative nurse education program in the Torres Strait Islands.
AB  - As the most numerous and geographically dispersed professional group, registered
      nurses in Australia work with Aboriginal and Torres Strait Islander health
      workers and other members of the multidisciplinary team in a variety of practice
      contexts to provide health care to Indigenous and non-Indigenous people. Despite
      the introduction of a variety of recruitment and proactive support strategies by
      employers, universities and State and Commonwealth governments, few Indigenous
      people in Australia enrol in, and graduate from, entry level higher education
      courses in the health professions. The reasons for this are complex and, as yet,
      not well understood or described; however, it is clear that the well-documented
      execrable health status of Indigenous Australians demands a response from
      universities, which are largely responsible for the education of health
      professionals. An innovative model of registered nurse education in the Torres
      Strait region of Australia is reported in this paper. A satellite campus
      established by James Cook University (JCU) on Thursday Island delivers the
      undergraduate nursing course by mixed mode, supplemented by specific strategies
      designed to improve Indigenous student recruitment and retention and thus
      increase the likelihood of graduation. The course and the strategies implemented
      are discussed in this paper.

PMID- 15967544
TI  - Insights into the mechanism of anti-tumor immunity in mice vaccinated with the
      human HER2/neu extracellular domain plus anti-HER2/neu IgG3-(IL-2) or anti
      HER2/neu IgG3-(GM-CSF) fusion protein.
AB  - In the present study, we demonstrate that a physical association between the
      extracellular domain of human HER2/neu receptor (ECDHER2) plus anti-HER2/neu IgG3
      (IL-2) or anti-HER2/neu IgG3-(GM-CSF) was required to elicit the most effective
      anti-tumor immune response against a syngeneic tumor expressing rat HER2/neu.
      Immune effectors including CD4+, CD8+, and NK cells contributed to protection
      against tumor growth. Vaccinated B-cell deficient mice did not elicit tumor
      protection, suggesting a critical role for B-cells in a protective immune
      response. These results provide insights into the mechanisms responsible for the
      protective tumor immunity elicited when antibody-(IL-2 or GM-CSF) are used as
      enhancers of vaccines targeting tumor antigens.

PMID- 15967545
TI  - Formalin-inactivated bovine RSV vaccine influences antibody levels in
      bronchoalveolar lavage fluid and disease outcome in experimentally infected
      calves.
AB  - Respiratory syncytial virus (RSV) causes severe respiratory disease in calves and
      human infants. In response to outbreaks, formalin inactivated (FI)-RSV vaccines
      were developed and found to exacerbate disease following a live RSV infection. We
      have reproduced vaccination induced disease enhancement in calves and screened
      various antibody isotypes in bronchoalveolar lavage fluid (BALF) from two
      studies: one with disease enhancement and another where moderate protection
      resulted from FI-bovine RSV (BRSV) vaccination. Semi-protected vaccinated calves
      produced BRSV-specific BALF IgG1, but not IgA and IgG2 prior to infection;
      whereas, calves with enhanced disease failed to develop BRSV-specific IgG1 in
      BALF. Ultimately, the formulation and delivery of RSV vaccines influences
      protective antibody levels in respiratory secretions.

PMID- 15967546
TI  - Case studies of three pregnant smokers and their use of nicotine replacement
      therapy.
AB  - OBJECTIVE: To examine the barriers encountered by pregnant women who attempt to
      stop smoking by highlighting three women who used nicotine patches. DESIGN: A
      randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of
      patches to test its acceptability for pregnant women. Ethics approval was granted
      despite NRT being contraindicated in Australia for pregnant women and having a
      low safety rating (category D) (Australian Drug Evaluation Committee, 1999).
      Salivary cotinine levels were used to assess nicotine exposure and provide some
      indicator of NRT safety. All participants were given pregnancy-specific cessation
      counselling, and the 20 women in the treatment arm were offered nicotine patches
      (15 mg/16 hr), with the option of weaning to lower strength patches if desired.
      SETTING: The Women's and Children's Hospital, Adelaide, a public tertiary
      teaching hospital in South Australia, with almost 4000 births annually. SAMPLE:
      40 'high-risk' pregnant smokers who expressed interest in stopping smoking.
      FINDINGS: As has been found in the general population, 'quit' rates with NRT use
      were low. Only three of the participants in this study, who became abstinent with
      patch use during pregnancy, were still abstinent at birth. The circumstances of
      two of these women, and a third woman who used patches to 'control' her smoking
      despite researcher advice, are detailed here. Only one of the two women
      'abstinent at delivery' was still abstinent 3 months after birth, the last
      contact point of the study. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:
      Although health providers intuitively regard pregnancy as an appropriate time for
      women to stop smoking, the stressors during pregnancy seem to militate against
      cessation. This study does not indicate that use of NRT will provide an easier
      solution. It may be more fruitful to institute a concerted lifestyle approach
      with both the woman and her partner (or significant household members), and
      continue this support and education postnatally if cessation has not been
      achieved. Health professionals should also support better-targeted public health
      campaigns and tobacco-control initiatives generally, because, undoubtedly, the
      social environment is a major determinant of initiation and continuation of
      smoking.

PMID- 15967547
TI  - The role of Tamang mothers-in-law in promoting breast feeding in Makwanpur
      District, Nepal.
AB  - OBJECTIVE: to systematically analyse the Nepalise grandmother's own perspective
      of breast feeding. DESIGN: a qualitative approach was used. Three focus-group
      discussions and eight semi-structured interviews formed the primary database. All
      interviews and discussions were tape recorded, and translated transcripts and
      field notes were analysed. SETTING: Makwanpur District, rural Nepal.
      PARTICIPANTS: 31 Tamang mothers-in-law living in a household with their son's
      family, and taking part in child care. FINDINGS: the data suggest that the
      mothers-in-law see themselves as key providers of, and decision-makers in,
      perinatal care practices. Traditional patterns of promotive and preventive care
      were identified. KEY CONCLUSIONS: contrary to the widespread reports that early
      breast feeding is delayed in this setting, these grandmothers held colostrum in
      high regard, used no prelacteals and supported early initiation of breast
      feeding.

PMID- 15967548
TI  - Women's needs from antenatal care in three European countries.
AB  - OBJECTIVE: To determine the important aspects of antenatal care from a woman's
      perspective in order to develop a woman-constructed conceptual model of antenatal
      care. DESIGN: Grounded theory. SETTING: Three European countries: Scotland,
      Switzerland and The Netherlands. PARTICIPANTS: 23 women using routine antenatal
      care in the three countries were interviewed: seven women in Scotland, seven in
      Switzerland and nine in The Netherlands. MEASUREMENTS AND FINDINGS: Three main
      categories emerged: 'responsibility', 'establishing a sharing trust relationship'
      and 'support me to be responsible'. The category of 'responsibility', which
      incorporated the sub-categories 'feeling confident' and 'feeling autonomous', is
      reported. Despite the many aspects that the women had in common, a divergence of
      the categories in each of the countries was clearly observed. The main cross
      cultural differences were within the sub-category of 'feeling autonomous'. KEY
      CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Responsibility is the main reason why
      women seek antenatal care. Feelings of confidence and autonomy are substantial
      attributes of this responsibility. The cultural background of the women seems to
      cause the differences within the categories. These findings have implications for
      both the provision and the evaluation of antenatal care.

PMID- 15967549
TI  - Emotion work and boundary maintenance in hospital-based midwifery.
AB  - OBJECTIVE: To identify and explore the emotion work of hospital-based midwives.
      DESIGN: An ethnographic approach using focus groups, observations and interviews.
      SETTING: South Wales, UK. PARTICIPANTS: Phase one of the study: self-selected
      convenience sample of 27 student midwives in first and final years of 3-year
      (direct entry) and 18-month (post-nursing) programmes. Phase two: opportunistic
      sample of seven qualified hospital-based midwives. Phase three: Purposive sample
      of 10 hospital-based midwives working within one National Health Service Trust.
      Sample representative of a range of clinical locations, length of clinical
      experience and clinical grades. FINDINGS: The emotion work of midwives was
      strongly influenced by the context of practice. For hospital-based midwives,
      relationships with midwifery colleagues were of key importance, providing the
      main source of feedback on individual practice. Negotiating these relationships
      was a major source of emotion work. Although collegial relationships could
      provide support and affirmation, they were also a frequent source of conflict,
      particularly between junior and senior midwives. This discord was underpinned by
      conflicting ideologies of midwifery practice. KEY CONCLUSIONS: The theoretical
      framework of boundary maintenance was used to interpret the findings. Senior and
      junior midwives frequently held contradictory models of practice, resulting in
      competing claims for occupational jurisdiction. Midwives made use of a variety of
      devices in order to establish and maintain intra-occupational boundaries. Senior
      midwives attempted to maintain their position through unwritten rules and
      sanctions, supported by their claim to greater clinical expertise and experience.
      Junior midwives rarely challenged this authority; their responses were often
      subversive and designed to create an appearance of compliance. IMPLICATIONS FOR
      PRACTICE: These findings contribute to our understanding of inter-collegial
      conflict in UK midwifery, providing insights into workplace harassment and low
      staff morale, which are likely to exacerbate workforce attrition. The
      underpinning ideological dissonance experienced by midwives must be acknowledged
      and tackled for these issues to be effectively addressed.

PMID- 15967550
TI  - Preliminary evaluation of a coping strategy enhancement method of preparation for
      labour.
AB  - OBJECTIVES: To compare the use and effects of enhanced pre-existing coping
      strategies with the use and effects of coping strategies usually taught in
      National Health Service (NHS) antenatal education on women's experience of pain
      and emotions during labour. DESIGN: A between-group comparison of women who chose
      to attend NHS antenatal education where courses of preparation were randomly
      assigned to include either a new method of coping strategy enhancement (CSE) or
      standard taught coping strategies. SETTING: Two large maternity units in one city
      in the North of England. PARTICIPANTS: 20 women participated in antenatal classes
      incorporating the CSE method and 21 women participated in antenatal classes
      incorporating the standard approach to developing coping strategies for labour.
      FINDINGS: Women who attended CSE classes used enhanced coping strategies for a
      larger proportion of their labour than women who attended standard classes who
      used taught coping strategies. Birth companions were more involved in women's use
      of enhanced than taught strategies. Self-efficacy for use of coping strategies
      and subsequent experiences of pain and emotions during labour were equivalent
      between groups. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: An approach based
      on enhancing pre-existing coping strategies was associated with greater coping
      strategy use and involvement from the birth companion, and provided benefits to
      women's overall experience of labour at least equivalent to that associated with
      standard preparation. Further research should explore this novel approach in
      larger groups, and for women who may choose not to attend group antenatal
      preparation.

PMID- 15967551
TI  - A critical ethnographic study of encounters between midwives and breast-feeding
      women in postnatal wards in England.
AB  - OBJECTIVE: To explore the nature of interactions between midwives and breast
      feeding women within postnatal wards. DESIGN: A critical ethnographic study using
      participant observation and focused interviews. SETTING: Two maternity units in
      Northern England, UK. PARTICIPANTS: 61 postnatal women and 39 midwives. FINDINGS:
      The interactions between midwives and women were encompassed by the global theme
      of 'taking time and touching base'. However, most encounters were characterised
      by an absence of 'taking time' or 'touching base'. This related to midwives'
      experiences of temporal pressure and inability to establish relationality with
      women due to their working patterns. The global theme was underpinned by five
      organising themes: 'communicating temporal pressure'; 'routines and procedures';
      'disconnected encounters'; 'managing breast feeding'; and 'rationing
      information'. KEY CONCLUSIONS: The organisational culture within the postnatal
      wards contributed to midwives experiencing profound temporal pressures and an
      inability to establish relationality with women. Within this context, the needs
      of breast-feeding women for emotional, esteem, informational and practical
      support were largely unmet. IMPLICATIONS FOR PRACTICE: Transformative action is
      required to dramatically reorganise the provision of hospital-based, postnatal
      ward midwifery care in parts of the UK. This should include a re
      conceptualisation of caring time, with recognition that midwives need sufficient
      time in order to give time to others. This, in turn, requires recognition that
      caring time is cyclical and rhythmical, allowing for relationality, sociability,
      mutuality and reciprocity. The midwifery staffing structure in postnatal wards
      needs to be reviewed, as it is unacceptable to midwives and service users for
      staff to be rapidly relocated according to other demands within the institution.
      Most radically, it is argued that now is the time to reconsider the suitability
      of the hospital as the place and space within which women commence their breast
      feeding journey.

PMID- 15967552
TI  - Are N and S deposition altering the mineral composition of Norway spruce and
      Scots pine needles in Finland?
AB  - Data from a large-scale foliar survey were used to calculate the extent to which
      N and S deposition determined the mineral composition of Scots pine and Norway
      spruce needles in Finland. Foliar data were available from 367 needle samples
      collected on 36 plots sampled almost annually between 1987 and 2000. A literature
      study of controlled experiments revealed that acidifying deposition mediates
      increasing N and S concentrations, and decreasing Mg:N and Ca:Al ratios in the
      needles. When this fingerprint for N and S elevated deposition on tree foliage
      was observed simultaneously with increased N and S inputs, it was considered
      sufficient evidence for assuming that acidifying deposition had altered the
      mineral composition of tree needles on that plot in the given year. Evidence for
      deposition-induced changes in the mineral composition of tree foliage was
      calculated on the basis of a simple frequency model. In the late eighties the
      evidence was found on 43% of the Norway spruce and 27% of Scots pine plots. The
      proportion of changed needle mineral composition decreased to below 8% for both
      species in the late nineties.

PMID- 15967553
TI  - Synthetic fibers as an indicator of land application of sludge.
AB  - Synthetic fabric fibers have been proposed as indicators of past spreading of
      wastewater sludge. Synthetic fiber detectability was examined in sludges
      (dewatered, pelletized, composted, alkaline-stabilized) and in soils from
      experimental columns and field sites applied with those sludge products. Fibers
      (isolated by water extraction and examined using polarized light microscopy) were
      detectable in sludge products and in soil columns over 5 years after application,
      retaining characteristics observed in the applied sludge. Concentrations mirrored
      (within a factor of 2) predictions based on soil dilution. Fibers were detectable
      in field site soils up to 15 years after application, again retaining the
      characteristics seen in sludge products. Concentrations correlated with residual
      sludge metal concentration gradients in a well-characterized field site. Fibers
      found along preferential flow paths and/or in horizons largely below the mixed
      layer suggest some potential for translocation. Synthetic fibers were shown to be
      rapid and semi-quantitative indicators of past sludge application.

PMID- 15967554
TI  - Emotional exposure in the treatment of substance use disorders: conceptual model,
      evidence, and future directions.
AB  - In this article, we review research on the nature and treatment of panic
      disorder, and apply these findings to a discussion of the role of internal cue
      exposure in the treatment of substance use disorders (SUDs). Two features of
      panic treatment were used as a model for interventions for SUDs: exposure to
      internal (interoceptive) cues rather than reliance on external (environmental)
      exposure alone, and use of cue exposure to try to inoculate individuals against
      future maladaptive patterns. Specifically, we emphasized the role of exposure to
      internal, largely emotional cues, as a way to enhance resilience to cues for
      relapse in individuals with SUDs. Hypothesized moderators and mediators of this
      treatment approach were discussed, as were similarities between this research
      agenda and an increasing focus on the role of emotional acceptance/tolerance in
      cognitive-behavioral treatments.

PMID- 15967555
TI  - Anxiety and stress vulnerability and substance problems: theory, empirical
      evidence, and directions for future research.
AB  - This introductory paper briefly reviews each of seven manuscripts in the present
      special series, the purpose of which was to provide a forum for the systematic
      presentation of theory, empirical evidence, and directions for future work as it
      pertains to anxiety and stress-related vulnerability processes and drug and
      alcohol problems. Articles in the series were selected to highlight a broad range
      of research on these topics. Whereas past work has largely focused on issues of
      psychiatric comorbidity, the articles in this series collectively suggest
      focusing on emotion vulnerability processes and the contexts in which they
      operate is a particularly valuable and promising pursuit. Each of the
      contributions also highlights the importance of developing models that explicitly
      integrate both basic and applied research in order to 1) effectively translate
      basic research findings to the applied realm, and 2) cast them in a nomological
      net. Finally, many of the articles noted that there is a pressing need to
      document theoretically relevant mediating and moderating processes involved with
      anxiety/stress and drug/alcohol problems in order to meaningfully move towards
      specialized intervention approaches.

PMID- 15967557
TI  - The social trajectory of illness: autism in the ultraorthodox community in
      Israel.
AB  - Severe or chronic illness-related events present patients and their family
      members with a physically and socially changed reality. In analyzing 30 open
      ended interviews of ultraorthodox Jewish Israeli mothers of children with autism,
      this paper addresses the general question of one childhood disorder's social
      trajectory and examines in particular mothers' efforts to promote their
      children's re-inclusion into the community. The illness narratives reveal the
      mothers' role as mediators between the child and the community, educating the
      child in religious praxis on the one hand and striving to bend social norms
      regarding this praxis to permit inclusion on the other. Despite these daily
      efforts, the ultraorthodox community challenges these children's status, and
      mothers turn to religious discourse to establish the status of the child with
      autism as an able Jewish individual. In utilizing spiritual discourse in daily
      activities, mothers only employ those cultural elements that advance the child's
      integration, thus further constructing small changes in religious themes. The
      findings highlight not only the mothers' role as mediators, but also their
      potential ability to set in motion processes of change.

PMID- 15967556
TI  - Is traumatic stress a vulnerability factor for women with substance use
      disorders?
AB  - The primary goal of this paper is to review existing findings from trauma,
      addictions and developmental research in order to delineate salient and
      outstanding questions for future research in this field. Toward this aim, our
      manuscript will provide an overview of the extant body of knowledge of
      trauma/PTSD comorbidity with substance use disorders and draw attention to
      converging developmental and neurobiological literature on the consequences of
      trauma on self-regulation. We conclude with suggestions for future research in
      these areas.

PMID- 15967558
TI  - Listening to those on the frontline: lessons for community-based tuberculosis
      programmes from a qualitative study in Swaziland.
AB  - This study explored the experience of people involved in a new community-based
      tuberculosis (TB) programme in rural Swaziland. Patients have their treatment
      observed in the community after choosing a treatment supporter (either community
      health worker or family member) in dialogue with the TB nurse. Interviews were
      conducted with TB patients, treatment supporters, clinic nurses, nurses working
      in the hospital-based TB team and medical staff. The study generated two main
      themes: (1) issues relating to the TB programme and (2) wider societal issues.
      Both are important, however this paper reports only the issues directly related
      to the TB programme. The study found that community-based care is preferred to
      hospital care, which should be retained only for the very ill patients. The
      importance of selecting suitable patients and ensuring individualised and
      flexible arrangements was highlighted. Although treatment outcomes are known to
      have improved since introducing the new TB programme a number of issues require
      further attention. Communication between different levels of the health service
      needs to be improved and consultation communication skills, taught prior to
      introducing the programme, need to be refreshed. All relevant staff must be
      trained on the TB programme and patient education (on TB, HIV and treatment
      adherence) needs to be reinforced throughout TB treatment. Health education of
      the wider community is also needed. Ongoing support of treatment supporters must
      recognise that their role is not simply treatment observation. In this context,
      where the large majority of TB patients are HIV positive, better co-ordination
      with the HIV/AIDS services is required, including treatment of other HIV-related
      infections and home-based care for TB patients who deteriorate. Although the
      findings and recommendations of this study are context specific they are likely
      to be of relevance to other programmes.

PMID- 15967559
TI  - The potential of schoolchildren as health change agents in rural western Kenya.
AB  - A prospective, quasi-experimental study was carried out in Bondo district in
      western Kenya to determine the potential of schoolchildren as health change
      agents in a rural community. A group of 40 schoolchildren were given health
      education using action-oriented and participatory approaches and their knowledge
      and practices as well as the influence on recipient groups consisting of peers at
      school and parents/guardians at home, were studied. The study, which used
      questionnaire surveys, involved a pre-test of knowledge about malaria, diarrhea
      and hygiene among the recipient groups. After the baseline surveys they underwent
      health communication training conducted by the 40 schoolchildren. An identical
      post-test questionnaire was administered to all participants at 4 and 14 months.
      Health-related practices were studied regularly through observation in schools
      and homes over 14 months. Significant improvement in knowledge was detected in
      all recipient groups. Behavioral changes were more evident among the children
      than among the adults. The impact of the project was reflected in concrete
      changes in the school environment as well as the home environments. The
      implications of the findings for health education projects and public health
      programs are outlined.

PMID- 15967560
TI  - N400 as an index of semantic expectancies: differential effects of alcohol and
      cocaine dependence.
AB  - BACKGROUND: Chronic substance abuse has been associated with decrements in the
      processing and expression of language. The present study utilized the N400 event
      related electroencephalographic potential to index semantic processing in 133
      adults with (n=49) or without (n=84) a history of alcohol and/or cocaine
      dependence. The contributions of age, gender, and comorbid marijuana and nicotine
      dependence, and antisocial symptomology to N400 decrements were either covaried
      or controlled. METHODS: A continuous series of 300 stimuli was presented for 150
      ms each (interstimulus interval=1475 ms) on a computer screen. The series was
      arranged such that a word (approximately 17% of stimuli) immediately preceded
      presentations of its antonym (primed condition; approximately 17% of stimuli), or
      a semantically unrelated word (unprimed condition; approximately 17% of stimuli).
      The remaining 50% of stimuli consisted of unpronounceable letter combinations
      (non-word condition). EEG responses to the antonyms, unrelated words, and letter
      jumbles were retained for analysis. Throughout the task, the subject pressed
      response keys to discriminate words from non-words. RESULTS: Analyses revealed a
      detrimental effect of alcohol dependence on N400 amplitude and no significant
      main or interactive effects of cocaine dependence. CONCLUSION: The present
      findings suggest that alcohol-dependent individuals may exhibit verbal processing
      decrements. These findings also challenge hypotheses suggesting that the combined
      use of cocaine and alcohol is more deleterious to brain function than alcohol use
      alone.

PMID- 15967561
TI  - Toxicological evaluation of glycerin as a cigarette ingredient.
AB  - Glycerin is applied to cigarette tobacco at levels in the range of about 1-5% to
      improve moisture holding characteristics of tobacco and act as a surface active
      agent for flavor application. Neat material pyrolysis studies, smoke chemistry
      and biological activity studies (bacterial mutagenicity, cytotoxicity, in vivo
      micronucleus, and sub-chronic rodent inhalation) with mainstream smoke, or
      mainstream smoke preparations from cigarettes containing various target levels
      (5%, 10%, and 15%) of the glycerin were performed to provide data for an
      assessment of the use of glycerin as a cigarette tobacco ingredient. The actual
      levels of glycerin in the respective test cigarettes were determined to be 3.2%,
      6.2% and 8.4% after cigarette production. At simulated tobacco burning
      temperatures up to 900 degrees C, neat glycerin did not pyrolyze extensively
      suggesting that glycerin would transfer intact to mainstream smoke (smoke was not
      analyzed for glycerin in this study). On a tar basis, nicotine in smoke was
      significantly decreased at 10% and 15% glycerin while water was increased at all
      addition levels. Addition of 10% or 15% glycerin also resulted in a statistically
      significant increase in acrolein (9%) and a decrease in acetaldehyde,
      propionaldehyde, aromatic amines, nitrogen oxides, tobacco specific nitrosamines,
      and phenols. Addition of 5% glycerin produced the same decrease in smoke
      constituents as the 10% and 15% groups but there was no concomitant increase in
      acrolein. Biological tests indicated no relevant differences in the genotoxic or
      cytotoxic potential of either mainstream smoke (or smoke preparations) from
      cigarettes with added glycerin compared to control cigarettes. Cigarette smoke
      atmosphere dilution, coupled with the lower nicotine delivery in the test
      cigarettes containing glycerin resulted in a lower nicotine delivery to the
      glycerin cigarette smoke exposed rats of the 90-day inhalation study. Smoke
      atmosphere acrolein was also reduced in a concentration-related manner.
      Incorporation of glycerin at target levels up to 15% did not produce any adverse
      effects in rats exposed for 90-days. The major observation in the study was a
      reduced biological activity of the smoke as indicated by a reduction in the
      severity and/or incidence of focal macrophage accumulation in the lungs and
      goblet cell hyperplasia/hypertrophy in the nose (level 1), and goblet cell
      staining depletion in the nose (level 1). The results of these studies with
      glycerin applied to cigarette tobacco suggest that adding glycerin to cigarette
      tobacco at typical use levels does not adversely alter the smoke chemistry or
      biological effects normally associated with exposure to mainstream cigarette
      smoke.

PMID- 15967562
TI  - The protective effect of caffeic acid phenethyl ester against cyclosporine A
      induced cardiotoxicity in rats.
AB  - Cyclosporine A (CsA) is the immunosuppressor, which is most frequently used in
      transplant surgery and in the treatment of autoimmune diseases. Oxidative stress
      has been considered as one of the possible mechanisms of CsA-induced
      cardiotoxicity. The present investigation examines the ability of caffeic acid
      phenethyl ester (CAPE), which is an active component of propolis extracts, as a
      natural antioxidant to protect against CsA-induced oxidative stress and
      cardiotoxicity. CsA cardiotoxicity was induced by subcutaneous injection of CsA
      at a dose of 15 mg/kg/body weight daily for 21 days in rats. Cardiotoxicity was
      evaluated by morphological and biochemical studies. CsA treated rats showed
      degenerative changes with cardiac fibrosis localized around the fibers. These
      latters were disorganised and the network was disappeared. The ROS production was
      increased whereas cytochrome-c-oxidase decreased. The expression and levels of
      matrix metalloproteinase 2 (MMP2) were increased whereas those of its inhibitor
      were downregulated. CAPE subcutaneous administration (15 micromol/kg/day)
      improved cardiac cytoarchitecture, decreased the levels and the expression of
      MMP2, and increased those of TIMP2 proteins. Moreover, it increased cytochrome-c
      oxidase activity and decreased ROS production. These results suggest that CAPE
      could have protective effect against CsA-induced cardiotoxicity.

PMID- 15967564
TI  - A predominant role for hydrogen bonding in the stability of the homodimer of
      bothropstoxin-I, A lysine 49-phospholipase A2.
AB  - Bothropstoxin-I (BthTx-I) is a homodimeric Lys49-phospholipase A(2) isolated from
      Bothrops jararacussu venom which damages liposome membranes via a Ca(2+)
      independent mechanism. The Glu12/Trp77/Lys80 triad at the dimer interface forms
      extensive intermolecular hydrogen bonds and hydrophobic contacts, and equilibrium
      chemical denaturation was used to evaluate the effect on homodimer stability of
      site-directed mutagenesis of these residues. Changes in the intrinsic
      fluorescence anisotropy and farUV circular dichroism signals were analyzed using
      a two-step unfolding model of the BthTx-I dimer to estimate the Gibbs free energy
      changes of transitions between the dimer and native monomer and between the
      native and denatured monomers. Whereas the Trp77His, Trp77Gln and Glu12Gln
      mutants showed native-like dimer stabilities, the Trp77Phe, Lys80Met and Lys80Gly
      mutants showed significantly reduced K(d) values. A reduced dimer stability is
      correlated with a decrease in the Ca(2+)-independent membrane damaging activity
      as monitored by the release of a liposome entrapped fluorescent marker. Although
      the membrane damaging activity of the monomer is fivefold less than the dimer,
      the myotoxic activity was unaffected, indicating that these two effects are not
      correlated. These data suggest that the BthTx-I dimer is predominantly stabilized
      by hydrogen bonding interactions, and highlight the importance of the homodimeric
      form for efficient Ca(2+)-independent membrane damage.

PMID- 15967565
TI  - Molecular cloning, expression, purification and characterization of calcineurin
      from bovine cardiac muscle.
AB  - Calcineurin (CaN), also known as calmodulin-dependent phosphatase, was cloned
      from bovine cardiac muscle and the deduced amino acid sequences of CaN A revealed
      that it had an open reading frame of 511 amino acid residues. As compared to
      bovine brain CaN A, the cardiac enzyme contains a 10 amino acid (ATVEAIEADE)
      deletion before the autoinhibitory region. A deletion analysis of the catalytic
      domain revealed a 20% decrease in phosphatase activity when the N-terminal 200
      amino acids were removed from CaN A as compared to the wild type enzyme. The C
      terminal deletions of CaN A revealed that in addition to the autoinhibitory
      domain (residues 457-480), additional adjacent residues (407-456) also inhibited
      CaN activity. These results point to either a second autoinhibitory region within
      CaN A or an extension of the previously noted autoinhibitory region within the
      cardiac CaN A enzyme.

PMID- 15967566
TI  - Proposals or findings for a new approach about how to define and diagnose
      premature ejaculation.
AB  - PURPOSE: To review and present the proposals or findings for a new approach about
      how to define and diagnose premature ejaculation (PE). MATERIALS AND METHODS:
      Using Medline to search for international peer reviewed manuscripts published
      from 1996 to 2004 about the definition and diagnosis of PE. RESULTS: PE, to date,
      has not a universally agreed definition and diagnostic criterion. Many
      definitions are partial, subjective and nonspecific. An ideal definition or
      diagnostic criterion should consist of intravaginal ejaculatory latency time
      (IELT), the ability to control over ejaculation, the extent of male sexual
      satisfaction, the extent of female sexual satisfaction, the frequency of female
      sexual partner reaching orgasm and the extent of psychological and pathological
      factors. Therefore, the Chinese Index of Premature Ejaculation (CIPE) seems an
      ideal tool and criterion used to diagnose PE due to including all the elements
      above. In the majority of cases, PE is the result of a mix of psychogenic,
      physiological and organic factors. So, besides some routine tests such as urine
      routine test, endocrine hormone assay, psychosexual counseling, couple evaluation
      and physical examination, prostate examination, serum leptin assay, semen
      magnesium assessment and glans hypersensitivity measurement, are suggested to be
      performed in the diagnosis of PE. Although elucidated by two clinical trials and
      further confirmed, serum leptin assay seems a promising and objective marker to
      diagnose PE because it is related to the serotonergic system whose disorder has
      been confirmed to contribute to the etiology of PE. CONCLUSION: None of these
      definitions and diagnoses has been accepted as a universal agreement of PE. CIPE
      seems an ideal tool and criterion used to diagnose PE and leptin maybe become a
      promising and objective marker for PE.

PMID- 15967567
TI  - Propiverine versus tolterodine: efficacy and tolerability in patients with
      overactive bladder.
AB  - OBJECTIVES: Propiverine and tolterodine were compared with respect to efficacy,
      tolerability and impact on the quality of life in the treatment of patients with
      idiopathic detrusor overactivity. METHODS: In a randomised, double-blind,
      multicentre clinical trial, patients with idiopathic detrusor overactivity were
      treated with 15 mg propiverine twice daily or 2mg tolterodine twice daily over a
      period of 28 days. The maximum cystometric capacity was determined at baseline
      and after 4 weeks of therapy. The difference of both values was used as the
      primary endpoint. Secondary endpoints were voided volume per micturition,
      evaluation of efficacy (by the investigator), tolerability, post void residual
      urine, and quality of life. RESULTS: The mean maximum cystometric capacity
      increased significantly (p < 0.01) in both groups. The volume at first urge and
      the frequency/volume chart parameters also showed relevant improvements during
      treatment. 42/100 patients in the propiverine group and 43/102 in the tolterodine
      group experienced adverse events. The most common adverse event, dry mouth,
      occurred in 20 patients in the propiverine group and in 19 patients in the
      tolterodine group. The scores for the quality of life improved comparably in both
      groups. CONCLUSION: The study demonstrates comparable efficacy, tolerability, and
      improvement in the quality of life of 15 mg propiverine twice-daily and 2mg
      tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor
      overactivity.

PMID- 15967568
TI  - An open, multicentre study of NASHA/Dx Gel (Zuidex) for the treatment of stress
      urinary incontinence.
AB  - OBJECTIVE: The Zuidex system facilitates non-endoscopic urethral injection for
      stress urinary incontinence (SUI). It comprises four pre-filled syringes of non
      animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel and an Implacer
      device. This open, 12-month study was performed to evaluate the safety and
      efficacy of this system in women with SUI. METHODS: Patients were aged > or =18
      years with a history of SUI for > or =12 months (hypermobility and/or intrinsic
      sphincter deficiency), had failed prior non-invasive therapy and were invasive
      therapy naive. Up to two treatments with NASHA/Dx gel were permissible (re
      treatment was offered at week 8). Positive response to treatment was defined as a
      reduction in provocation test leakage of > or =50% compared with baseline.
      Efficacy was also measured by 24-hour pad weight test leakage, and number of
      incontinence episodes/24 hours. RESULTS: A total of 142 patients were enrolled,
      with a mean age of 55.7 years. The response rate was 78% at week 12, and 77% at
      month 12. Significant reductions in median provocation test leakage, 24-hour pad
      weight test leakage and number of incontinence episodes/24 hours were observed at
      all time-points. At month 12, the median decreases from baseline in these three
      variables were 93%, 89% and 67%, respectively. Treatment-related adverse events
      were of a nature expected with urethral injection - most were transient, and of
      mild or moderate intensity. CONCLUSIONS: Treatment with NASHA/Dx gel produced
      large, statistically significant reductions in urinary leakage sustained over 12
      months and was well tolerated. These findings suggest that NASHA/Dx gel could be
      considered as an early intervention in treatment-naive cases of SUI.

PMID- 15967569
TI  - Imperfect DNA mirror repeats in E. coli TnsA and other protein-coding DNA.
AB  - DNA imperfect mirror repeats (DNA-IMRs) are ubiquitous in protein-coding DNA.
      However, they overlap and often have different centers of symmetry, making it
      difficult to evaluate their relationship to each other and to specific DNA and
      protein motifs and structures. This paper describes a systematic method of
      determining a hierarchy for DNA-IMRs and evaluates their relationship to protein
      structural elements (PSEs)--helices, turns and beta-sheets. DNA-IMRs are
      identifed by two different methods--DNA-IMRs terminated by reverse dinucleotides
      (rd-IMRs) and DNA-IMRs terminated by a single (mono) matching nucleotide (m
      IMRs). Both rd-IMRs and m-IMRs are evaluated in 17 proteins, and illustrated in
      detail for TnsA. For each of the proteins, Fisher's exact test (FET) is used to
      measure the coincidence between the terminal dinucleotides of rd-IMRs and the
      terminal amino acids of individual PSEs. A significant correlation over a span of
      about 3 nt was found for each protein. The correlation is robust and for most
      genes, all rd-IMRs<or=13 nt can be removed without the loss of statistical
      significance. In TnsA, the protein intervals translated by rd-IMRs>16 nt contain
      approximately 88% of the potential functional motifs. The protein translation of
      the longest rd- and m-IMRs span sequences important to the protein's structure
      and function. In all 17 proteins studied, the population of rd-IMRs is
      substantially less than the expected number and the population of m-IMRs greater
      than the expected number, indicating strong selective pressures. The association
      of rd-IMRs with PSEs restricts their spatial distribution, and therefore, their
      number. The greater than predicted number of m-IMRs indicates that DNA symmetry
      exists throughout the entire protein-coding region and may stabilize the
      sequence.

PMID- 15967570
TI  - Nitric oxide-dependent activation of pig oocytes: role of calcium.
AB  - Pig oocytes matured in vitro are parthenogenetically activated after treatment
      with nitric oxide (NO)-donor SNAP. The chelation of intracellular calcium ions
      with BAPTA-AM suppressed the SNAP-induced activation in a dose-dependent manner.
      Activation by a NO-donor is dependent on the influx of calcium from extracellular
      spaces, because the blockage of calcium channels by verapamil had significantly
      reduced the activation rate in SNAP-treated oocytes. The blockage of inositol
      triphosphate receptors had no effect on the activation of oocytes by a NO-donor.
      On the other hand, the blockers of ryanodine receptors, procaine and ruthenium
      red, inhibited the activation of oocytes induced by a NO-donor. These data
      indicate that the activation of pig oocytes by a NO-donor is calcium-dependent.
      The calcium for the activation is mobilized from extracellular and intracellular
      spaces. For the mobilization of intracellular calcium stores, it is the ryanodine
      receptors and not the inositol triphosphate receptors that play a key role.

PMID- 15967571
TI  - Measurement and relevance of neuroblastoma DNA copy number changes in the post
      genome era.
AB  - The completion of the human genome sequence and the development of high
      throughput technology present exciting opportunities for the study of cancer
      cells. High-resolution analysis of chromosomal aberrations provides a global
      framework for understanding complex patterns in cancer cells, allowing us to ask
      hypothesis-driven questions. Genome-wide analysis of amplification and deletion
      of genomic regions is a critical step to resolving the mechanisms of
      neuroblastoma tumorigenesis. We used a high-resolution aCGH system that has over
      4000 human BAC clones, resulting in an average coverage of 1Mb across the genome,
      to define whole genome copy number aberrations (CNAs) in a panel of human
      neuroblastoma-derived cell lines. By combining the aCGH data with meticulous
      regional validation studies, we showed that array CGH could reliably detect known
      aberrations including single copy gain or loss, that data correlate well with
      standard techniques used for the detection of these genetic changes, and that
      this technique can be used to identify novel regions of genomic imbalance.

PMID- 15967572
TI  - SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion.
AB  - Glioma cells produce vascular endothelial growth factor (VEGF) to induce
      vascularization and thereby supply the malignant tissue with oxygen and
      nutrients. However, little is known about the direct effects of VEGF on tumor
      cells. In this study, we investigate the ability of VEGF to promote proliferation
      and invasion of human glioma cells (U251n). Since the chemokine and its receptor,
      SDF-1/CXCR4, promote glioma cell proliferation and are up-regulated in human
      glioblastomas, we also tested the effects of VEGF on SDF-1 and CXCR4 mRNA
      expression. Using cell culture, the effect of VEGF on proliferation of U251n
      cells was measured using ELISA to detect incorporated BrdU as a marker of DNA
      syntheses. The effects of VEGF and SDF-1 on U251n cell invasion and proliferation
      were measured using inhibitors to VEGF receptor1 and receptor2, DC101 and MF1,
      respectively, and a CXCR4 antagonist (AMD3100). SDF-1 and CXCR4 mRNA expression
      in U251n and U87MG cells were measured using quantitative PCR. VEGF antisense
      phosphorothioate oligodeoxynucleotide (AS-VEGF) was also used to down-regulate
      VEGF expression in U251n cells. VEGF significantly increased U251n cell
      proliferation and invasion in a dose-dependent manner. These effects were blocked
      by the VEGF receptor inhibitors, DC101/MF1. The CXCR4 antagonist AMD3100 blocked
      U251n increased invasion, but not proliferation. CXCR4 and SDF-1 mRNA were up
      regulated when U251n and U87MG cells were treated with VEGF. Eight micrometer
      VEGF antisense phosphorothioate oligodeoxynucleotide (AS-VEGF) down-regulated
      CXCR4 and SDF-1 mRNA levels in U251n cells. VEGF has a direct effect on U251n
      glioma cell proliferation and invasion. VEGF up-regulates SDF-1 and CXCR4 mRNA
      expression, and contributes to U251n cell invasion.

PMID- 15967573
TI  - Polyphenol associated-DNA adducts in lung and blood mononuclear cells from lung
      cancer patients.
AB  - The formation of smoking induced-DNA adducts is a critical factor in the
      induction of human lung cancer. As derivates of benzene and polyaromatic
      hydrocarbons (PAHs) are important compounds of tobacco smoke, in DNA isolated
      from human lung and blood mononuclear cells (MNCs) from 38 lung cancer patients,
      we used the (32)P-postlabeling assay to detect polyphenol associated DNA adducts.
      Two DNA adducts were detected in blood MNCs and lung tissue that co
      chromatographed with DNA modifications from HL60 cells treated with combinations
      of benzene metabolites (e.g., hydroquinone and benzenetriol). These adducts were
      designated polyphenol-associated DNA adducts. Relative adduct levels for
      polyphenolic adducts were five-fold higher than aromatic adducts in both lung and
      MNCs. A significant correlation was observed between levels of polyphenol adducts
      and total duration of cigarette smoking in lung (r=0.34; P<0.04) and MNCs (r=0.7;
      P<0.04), but no correlation between levels of polyphenol adducts and pack-years
      consumption of cigarettes nor time since quitting smoking in former smokers. Long
      term former smokers and the one non-smoker in the study had detectable levels of
      polyphenol adducts. Surprisingly, the levels of polyphenol adducts in MNCs were
      highly correlated with aromatic adduct levels (r=0.84; P<0.001). Individual
      aromatic adducts in MNCs also correlated with polyphenol adducts. Total
      polyphenol adduct levels had a correlation with aromatic DNA adduct levels in
      lung tissue (r=0.46; P<0.01). To our knowledge these results are the only
      comparison of adducts in MNCs with lung tissue, and the only data set indicating
      that blood MNCs are a valid surrogate for lung adduct DNA burden.

PMID- 15967574
TI  - Evaluation of levetiracetam effects on pilocarpine-induced seizures: cholinergic
      muscarinic system involvement.
AB  - Levetiracetam (LEV) is a new antiepileptic drug effective as adjunctive therapy
      for partial seizures. It displays a unique pharmacological profile against
      experimental models of seizures, including pilocarpine-induced seizures in
      rodents. Aiming to clarify if anticonvulsant activity of LEV occurs due to
      cholinergic alterations, adult male mice received LEV injections before
      cholinergic agonists' administration. Pretreatment with LEV (30-200 mg/kg, i.p.)
      increased the latencies of seizures, but decreased status epilepticus and death
      on the seizure model induced by pilocarpine, 400 mg/kg, s.c. (P400). LEV (LEV200,
      200 mg/kg, i.p.) pretreatment also reduced the intensity of tremors induced by
      oxotremorine (0.5 mg/kg, i.p). [3H]-N-methylscopolamine-binding assays in mice
      hippocampus showed that LEV200 pretreatment reverts the downregulation on
      muscarinic acetylcholine receptors (mAChR), induced by P400 administration,
      bringing back these density values to control ones (0.9% NaCl, i.p.). However,
      subtype-specific-binding assays revealed that P400- and LEV-alone treatments
      result in M1 and M2 subtypes decrease, respectively. The agonist-like behavior of
      LEV on the inhibitory M2 mAChR subtype, observed in this work, could contribute
      to explain the reduction on oxotremorine-induced tremors and the delay on
      pilocarpine-induced seizures, by an increase in the attenuation of neuronal
      activity mediated by the M1 receptors.

PMID- 15967575
TI  - Dynamics of neurogenesis in the dentate gyrus of adult rats.
AB  - Hippocampal neurogenesis declines steadily over the first year of life in the
      rodent, but the process persists into senescence despite a dramatic drop in the
      number of neurons it produces. At this point though, the survival and development
      patterns exhibited by new granule cells in the aging brain remain unclear in
      relation to patterns observed in the younger brain. The present study was carried
      out in order to obtain a direct quantitative comparison of hippocampal
      neurogenesis in juvenile and middle-aged rats with a high degree of temporal
      resolution, and to compare the survival and differentiation of the new cells over
      time. Thirty-eight-day-old and 12-month-old, male Sprague--Dawley rats were
      injected with 5-bromo-2'-deoxyuridine (BrdU) in order to label cells dividing in
      the dentate gyrus over a 24-h period, and immunohistochemical labeling was
      performed in order to record cell production and survival at eight different time
      points over the following two-month period. Using a marker of neuronally
      committed precursors and immature neurons (doublecortin; DCX), as well as a
      marker of mature neurons (calbindin d-28K; CaBP), the extent and timeline of
      neuronal differentiation, maturation, and migration of the new cells were also
      characterized. Results indicated that 12-month-old rats experienced a nearly 94%
      reduction in neurogenesis relative to juveniles, due almost entirely to a 92%
      drop in cell production. A largely preserved course of development and migration
      in the remaining newborn cells suggests treatments that enhance cell
      proliferation could be crucial in reversing the age-related decline in
      neurogenesis.

PMID- 15967576
TI  - Canine visceral leishmaniasis in Sao Jose de Ribamar, Maranhao State, Brazil.
AB  - Here, we describe the situation of canine visceral leishmaniasis in two villages
      of Sao Jose de Ribamar in Maranhao State/Brazil, where human cases have been
      registered. Blood samples of 36 household crossbred dogs from Sergio Tamer
      village and 43 dogs from Quinta village were collected and the serum used for
      serological diagnosis. An Indirect Fluorescent Antibody Test (IFAT) and enzyme
      linked immunosorbent assay (ELISA) were used to detect antibodies against
      Leishmania. The clinical examination showed that 25% of the canine population of
      Quinta presented a poor body condition and in 39%, ectoparasites (ticks and
      fleas) were detected. In both tests, serology revealed that 21% (9 out of 43) of
      the dogs presented antibodies against Leishmania (55% were asymptomatic and 45%
      were symptomatic). In the Vila Sergio Tamer, 25% (9 out of 36) of the dogs were
      seropositive for Leishmania (66.67% were asymptomatic and 33.33% were
      symptomatic), 33% presented poor body condition, and 22% have ectoparasites. The
      clinical signs more frequent were skin lesions. The statistical analysis showed
      that there was no statistical difference (p>0.05) between the seropositivity of
      the dogs from the two villages. The same was observed when the clinical signs
      were compared (p>0.05). Both villages have favorable conditions to maintain the
      cycle of leishmaniasis.

PMID- 15967577
TI  - Biochemical characterization of an effective substrate and potent activators of
      CK2 copurified with Bowman-Birk-type proteinase inhibitor from soybean seeds in
      vitro.
AB  - By means of Mono P column chromatography, an effective phosphate acceptor (EPA)
      of casein kinase 2 (CK2) was purified from the Bowman-Birk-type proteinase
      inhibitor (BBI) fraction of soybean seeds. The most acidic EPA (aEPA, pI=approx.
      3.7) was heavily phosphorylated when incubated with CK2 and 5 microM [gamma
      (32)P]ATP in the presence of poly-Arg (a CK2 activator) in vitro. However, aEPA
      was slightly phosphorylated by casein kinase 1 (CK1) as effective as C-kinase and
      not at all by A-kinase in vitro. The 13 N-terminal amino acid residues
      (SDHSSSDDESSKP) of aEPA were 100% homologous to the corresponding sequence of
      soybean BBI-type proteinase inhibitor CII (SBI CII). Polyamine at 3 mM stimulated
      4.6-fold the CK2-mediated phosphorylation of aEPA, and this phosphorylation was
      sensitive to quercetin (ID(50)=approx. 0.1 microM) in vitro. Furthermore, two
      basic proteins [Mr=29,000 (p29) and 17,000 (p17)] copurified with BBI were
      identified as proteolytic cleavage products of basic 7S globulin and functioned
      as potent CK2 activators in vitro. aEPA fully phosphorylated by CK2 in the
      presence of poly-Arg or basic proteins formed a complex with trypsin, whereas
      unphosphorylated aEPA was digested by trypsin in vitro. These results suggest
      that (i) aEPA (a BBI isoform) may coexist with two basic proteins (p29 and p17)
      generated from basic 7S globulin; and (ii) the physiological interaction between
      aEPA and its binding trypsin-like proteinases may be regulated through specific
      phosphorylation of aEPA by CK2 activated with the two basic proteins in legume
      seeds.

PMID- 15967578
TI  - Interaction of an amphitropic protein (factor Xa) with membrane models in a
      complex system.
AB  - Phosphatidylserine (PS) plays a crucial role, in the conversion of prothrombin
      into thrombin by the protease, factor Xa. Physiologically, the conversion occurs
      in the prothrombinase complex. The question of how water-soluble proteins that
      normally circulate in plasma bind remains to be unambiguously determined. We
      previously found that the amphitropic proteins (prothrombin, factors V and Va)
      penetrate into phospholipid layers. AC polarography has allowed the detection for
      the first time of insertion of factor Xa into condensed monolayers containing
      phosphatidylserine (PS) and phosphatidylcholine (PC) either 100% PS or 25% PS in
      the presence of Ca2+. This observation demonstrates that part of factor Xa can
      cross the phospholipid polar headgroup/hydrocarbon chain interface. In parallel
      experiments, radioactive surface measurements permitted measuring binding of
      tritium-labeled factor Xa onto a PS monolayer and calculate an association
      constant, 6x10(6) M(-1). Penetration of factor Xa into PS-containing vesicles was
      investigated also using photoactivable 5-[125I]iodonaphthalene-1-azide, which
      binds selectively to the lipid embedded domains of the protein. These experiments
      suggest that Factor Xa penetrates preferentially by its heavy chain, an
      alternative mode of binding to the commonly accepted binding via its Gla domain.
      Interaction of factor Xa with PS vesicles also changes its apparent K(m) for S
      2222.

PMID- 15967579
TI  - Selenocysteine in proteins-properties and biotechnological use.
AB  - Selenocysteine (Sec), the 21st amino acid, exists naturally in all kingdoms of
      life as the defining entity of selenoproteins. Sec is a cysteine (Cys) residue
      analogue with a selenium-containing selenol group in place of the sulfur
      containing thiol group in Cys. The selenium atom gives Sec quite different
      properties from Cys. The most obvious difference is the lower pK(a) of Sec, and
      Sec is also a stronger nucleophile than Cys. Proteins naturally containing Sec
      are often enzymes, employing the reactivity of the Sec residue during the
      catalytic cycle and therefore Sec is normally essential for their catalytic
      efficiencies. Other unique features of Sec, not shared by any of the other 20
      common amino acids, derive from the atomic weight and chemical properties of
      selenium and the particular occurrence and properties of its stable and
      radioactive isotopes. Sec is, moreover, incorporated into proteins by an
      expansion of the genetic code as the translation of selenoproteins involves the
      decoding of a UGA codon, otherwise being a termination codon. In this review, we
      will describe the different unique properties of Sec and we will discuss the
      prerequisites for selenoprotein production as well as the possible use of Sec
      introduction into proteins for biotechnological applications. These include
      residue-specific radiolabeling with gamma or positron emitters, the use of Sec as
      a reactive handle for electophilic probes introducing fluorescence or other
      peptide conjugates, as the basis for affinity purification of recombinant
      proteins, the trapping of folding intermediates, improved phasing in X-ray
      crystallography, introduction of 77Se for NMR spectroscopy, or, finally, the
      analysis or tailoring of enzymatic reactions involving thiol or oxidoreductase
      (redox) selenolate chemistry.

PMID- 15967580
TI  - Cement burns: retrospective study of 18 cases and review of the literature.
AB  - SUBJECT: Cement is increasingly used in the construction industry, but the
      occurrence of cement burns is rarely reported. This retrospective study concerns
      patients treated for cement burns in our unit between 1997 and 2002. MATERIALS
      AND METHODS: Eighteen patients 18-64 years of age, treated previously in our unit
      for cement burns, were interviewed by telephone for evaluation. RESULTS: The mean
      time since treatment was 39 months. Burns were predominantly seen on the lower
      limbs, and a third occurred during an accident on the job. All deep burns were
      excised, and 16 patients received grafts. Mean hospital stay was 10 days, and
      mean sick leave 2 months. Our study indicated that all patients were poorly
      informed about cement-related risks. DISCUSSION: Surgical treatment of full
      thickness cement burns at diagnosis enables rapid healing with a minimum of
      sequelae and reduces the high socioeconomic costs resulting from these lesions.
      CONCLUSION: This study indicates once again the need to improve preventive
      measures; which are very often inadequate because of lack of awareness of risks.

PMID- 15967581
TI  - Burn care standards in Israel: lack of consensus.
AB  - In recent years, the need for a national burn center based on ABA guidelines has
      emerged in Israel. The formation of such a center is now underway in the Chaim
      Sheba Medical Center. As a first step in the standardization of burn care in
      Israel, we have conducted a nation-wide survey among burn care personnel
      (physicians, nurses and other burn team members), regarding different aspects of
      the treatment of burn patients. METHODS: A questionnaire comprised of 30
      questions regarding the severity of burns admitted, the site of initial
      management, wound care (both burn/skin-graft sites and donor sites), dressing
      changes protocols, sterility precautions, hydrotherapy, and pressure dressings
      was presented to 70 health-care professionals involved in the treatment of burns.
      RESULTS AND DISCUSSION: Seventy-seven percent of interviewed personnel
      participated in the survey. Consensus was found regarding most local (topical)
      wound care, (SSD for clean non-facial burns, Sulfamylon (mafenide-acetate) for
      contaminated non-facial burns, Threolone (chloramphenicol 3% and prednisolone
      0.5%) or Bacitracin for facial burns, Paraffin gauzes with or without Sulfamylon
      for donor and graft sites). Dressing changes regimes were also agreed upon
      generally. However, there was no consensus regarding the ideal time for the
      removal of donor site dressings and this issue will need to be resolved. Other
      important findings are that both Edinborough University Solution of Lime (EUSOL),
      which has been deemed unsuitable for burn treatment due to toxic effects, and
      hydrotherapy, which has been proposed as a source of infection and contamination,
      are still widely used. We anticipate that these issues will be settled in our
      unified national burn care protocols (which are currently under development and
      revision).

PMID- 15967582
TI  - Cancer in the older person.
AB  - Cancer in the older person is an increasingly common problem, due to the
      progressive prolongation of the life-expectancy of the Western population. This
      article reviews the mechanisms associating aging and cancer, age-related changes
      in cancer biology, assessment of the older person to estimate life-expectancy,
      treatment tolerance, and medical and social conditions that may interfere with
      cancer treatment, effectiveness of cancer prevention and cancer treatment in
      older individuals. A comprehensive geriatric assessment (CGA) is commonly used to
      predict life-expectancy and functional reserve and to unearth conditions that may
      jeopardize cancer prevention and treatment. In the interest of cost and time,
      shortened forms of CGA are being explored. Chemoprevention of cancer is a
      promising form of prevention that at present has no conclusive clinical
      indications. Early diagnosis of breast and colon cancer through screening of
      asymptomatic patients at risk may be beneficial for individuals with a life
      expectancy of 5 years or longer. Early detection of lung cancer in ex-smokers is
      undergoing clinical trials, as this disease is becoming more and more common. Age
      should not prevent appropriate treatment of cancer in older individuals,
      especially in those with adequate life-expectancy and functional reserve. The
      National Cancer Center Network (NCCN) has issued a series of guidelines to
      minimize the toxicity and promote the effectiveness of cancer in older patients.
      Important interventions include prevention of neutropaenic infections with
      filgrastim and peg-filgrastim, prevention of anaemia with epoietin or
      darbepoietin, and prevention and early management of mucositis.

PMID- 15967583
TI  - General and smoking cessation related weight concerns in veterans.
AB  - This study sought to assess general and cessation related weight concerns in
      Veterans presenting for QuitSmart, a tobacco cessation program used extensively
      in the Veteran Affairs system. Assessed were prevalence rates of cessation
      related weight concerns, the weight at which concerned Veterans would relapse to
      smoking, characteristics of weight concerned Veterans, and the impact of weight
      concerns on cessation at the program's end and at the 1-month follow-up. Sixty
      seven Veterans participated. Of those, 63 were eligible for cessation analyses.
      Results suggested that 26.9% were concerned about post-cessation weight gain, the
      mean and median weights tolerated before relapse were in the 10-12 lb range, and
      weight concerned Veterans were more likely younger with more general weight
      concerns. At both time points, Veterans with general weight concerns were much
      more likely to quit smoking than those without such concerns. At neither time
      point, were post-cessation weight concerns significantly associated with quit
      status, though specific concerns remained in predictive models and trends
      suggested those with cessation related weight concerns were less likely to quit
      smoking than those without such concerns. Results suggest a significant
      prevalence rate of general and cessation related weight concerns in Veterans
      attempting to quit smoking, greater success in doing so if weight concerns are
      general in nature, and the need to continue to assess these relationships and
      develop effective cessation treatments for this population.

PMID- 15967584
TI  - Psychiatric severity and mortality in substance abusers: a 15-year follow-up of
      drug users.
AB  - Previous research has shown that most transitions into abstinence happens in the
      stages of the drug career quickly after the first treatment episode. Mortality is
      somewhat reduced for patients who become abstinent, but remains high for patients
      who remain addicted. However, even among substance abusers who become abstinent,
      mortality is often higher than in the general population. A consecutive sample of
      drug users admitted for detoxification was followed for 15 years. Face-to-face
      interviews were conducted at 5-year follow-up. At 15-year follow-up, 24% were
      dead. Cox proportional hazard regression was conducted to predict mortality for
      continuous variables, and Gehan's Wilcoxon test was used to predict mortality for
      dichotomous variables. Psychiatric status at 5-year follow-up was predictive of
      15-year mortality, whereas abstinence was not. Subjects who later died had higher
      scores on the Symptom Checklist 90 [SCL-90] Global Severity Index, lower
      meaningfulness on the Sense of Coherence scale, and lower Global Assessment of
      Functioning [GAF] scores at 5-year follow-up. By contrast, there were no
      associations between baseline drug use and antisocial personality disorder
      diagnoses and mortality. Psychiatric treatment, including psychotherapy, may be
      more life-saving for substance abusers than drug-abuse services.

PMID- 15967585
TI  - Psychological differences between binge and chronic methamphetamine using gay and
      bisexual men.
AB  - Methamphetamine use among gay and bisexual men in New York City continues to
      pervade the psychological and physical well being of those who engage in its use.
      While the behavioral and contextual factors associated with methamphetamine use
      have been examined, there is a paucity of literature examining the psychological
      and psychosocial correlates associated with varying levels of addiction to the
      substance. We assessed these correlates among 49 methamphetamine-using gay and
      bisexual men in New York City. Findings suggest that "Chronic" users report
      higher levels of avoidant coping and are more likely to use methamphetamine to
      avoid unpleasant emotions, to avoid physical pain, and to engage in pleasant
      times with others than those who are "Binge" users. While previous research
      demonstrates the value of treatment approaches that consider the synergy of
      mental health, drug use, and sexual-risk taking, our findings suggest the
      importance of identifying the frequency and current progression of
      methamphetamine use when addressing the psychological meanings it has for the
      individual user.

PMID- 15967586
TI  - Joint trajectories of gambling, alcohol and marijuana use during adolescence: a
      person- and variable-centered developmental approach.
AB  - The usefulness of Moffitt's (1993) [Moffitt, T. E. (1993). Adolescence-limited
      and life-course-persistent antisocial behavior: A developmental taxonomy.
      Psychological Review, 100, 674-701.] theory of antisocial behavior was examined
      regarding gambling, alcohol and marijuana use. We assessed 903 Caucasian boys'
      developmental trajectories of these behaviors annually from age 11 through age
      16. Severity of problems with these behaviors were assessed at ages 17 and 23. As
      correlates of these behaviors, teacher-rated personality and self-reported
      parenting were assessed at age 10. Self-reported autonomy was measured at ages 11
      and 14. A cluster analysis on the correlates yielded two clusters. Membership in
      the cluster without adult problems was associated with either late onset of
      gambling and/or alcohol use trajectories or consistently low involvement in each
      of the behaviors. This cluster may correspond to Moffitt's adolescence-limited
      group and uninvolved adolescents, respectively. Membership in the cluster with
      subsequent adult problems was associated with early initiation of at least one of
      the three behaviors and involvement in each of them during adolescence. This
      cluster may correspond to Moffitt's life-course-persistent group. Findings
      indicate that early assessment of correlates used in the cluster analysis may be
      useful for screening and preventive purposes.

PMID- 15967587
TI  - Replication of subtypes for smoking cessation within the Preparation stage of
      change.
AB  - OBJECTIVE: Recent cluster analyses based on the Pros and Cons and the Situational
      Temptations measures performed within the stages of change defined by the
      Transtheoretical Model have suggested the existence of distinct cluster subtypes.
      The goal of this study is to replicate cluster subtypes within the Preparation
      stage of change in a secondary analysis of data from a sample of current smokers
      (N=3967). Identification of stable cluster subtypes would permit the development
      of tailored interventions focusing on these subtypes. METHOD: Two random samples
      of approximately 340 subjects were selected from the 686 participants in the
      Preparation stage. The cluster analyses were performed using the Pros, Cons and
      Situational Temptations. Interpretability of the pattern, pseudo F test, and
      dendograms were used to determine the number of clusters. RESULTS: Four distinct
      cluster subtypes (Classic, Progressing, Early Preparation, and Disengaged) were
      found and replicated across samples. The clusters were externally validated using
      the ten processes of change and two smoking behavior variables. Statistically
      significant (p<0.05) multivariate effects were found for the ten processes of
      change and the smoking behavior variables (p<0.001) in the two samples.
      CONCLUSIONS: The cluster patterns replicate earlier findings and provide evidence
      for the existence of clusters subtypes within the Preparation stage of change.

PMID- 15967588
TI  - Self-change: A pathway to cannabis abuse resolution.
AB  - Long-term daily cannabis abusers (N = 25) who without treatment stopped using
      cannabis for at least one year were interviewed about their past substance use,
      antecedents to change, and factors supportive of change. Respondents' cannabis
      problems decreased in the year prior to their recovery compared to their lifetime
      use. Respondents described their successful quit attempts through structured
      interviews and autobiographical narratives. The narratives were content analyzed
      for factors related to recovery. The reports indicated that marijuana cessation
      was motivated more by internal than external factors, and the most common
      precipitants of quit attempts were cognitive anti-cannabis factors. The major
      reason reported by respondents for stopping cannabis was a change in how they
      viewed their cannabis use, followed by negative personal effects. The most common
      reported maintenance factors were avoidance of situations in which cannabis was
      used, changes in lifestyle, and the development of non-cannabis-related
      interests. Cognitive and respiratory functioning were also assessed. Lastly, more
      than 75% of respondents reported not seeking treatment because they believed it
      was not needed or because they wanted to quit on their own. Directions for future
      research are offered.

PMID- 15967589
TI  - Diabetes mellitus, tuberculosis and the mycobacteria: two millenia of enigma.
AB  - The thought that tuberculosis and the mycobacteria could cause diabetes seems
      farfetched, but is not. The peculiar relationship and frequent association of
      diabetes mellitus and tuberculosis has been observed for more than 2000 years,
      yet the reason for this correlation is, to this day, not known. Before the
      discovery of insulin, a diagnosis of diabetes was a death sentence within 5
      years, and the usual cause of that death was tuberculosis. Despite this, in the
      5th century, tuberculosis was already being portrayed as a "complication" of
      diabetes, a view little changed to this day, parroting Root's original 1934
      description of "a one-sided relationship": tuberculosis still seen as a common
      complication of diabetes, while diabetes is thought to be no more common among TB
      patients than in the population at large. To Nichol's, this was "not logically
      tenable" and in his study of 178 otherwise healthy, non-diabetic military men
      with tuberculosis at Fitzsimmons Army Hospital, one-third had abnormal glucose
      screening tests. But despite his findings and those of Reaud in New York and
      others, this was not being recognized elsewhere, and Nichols wanted to know why.
      Nichols concluded that the incidence of diabetes among tuberculosis patients was
      considerably underestimated and that in tuberculosis patients, diabetes develops
      quite commonly. Diabetes was easy to detect. Tuberculosis and the mycobacteria
      were not. The evidence for a mycobacterial cause of diabetes is mounting rapidly.
      Schwartz and Haas both linked Type-2 diabetes to tuberculosis. And the pancreatic
      islet amyloid deposits that they found as a by-product of systemic tubercular
      infection have recently been dissolved by rifampicin, a first line drug against
      tuberculosis. Engelbach spoke of "transitory" diabetes in TB and Karachunskii
      noted changes in carbohydrate metabolism in patients with tuberculosis which
      commonly led to insulin deficiency with persistent hyperglycemia. Furthermore,
      mycobacterial elements have been shown recently not only to cause "autoimmune"
      Type-1 diabetes in NOD (non-obese diabetic) mice, but act as a vaccine to stop
      the inevitable diabetes that would otherwise materialize. The documentation of
      patient cases where TB has preceded and come before the development of diabetes
      is extensive yet underplayed and both Lin's and Tsai's studies speak of
      tuberculosis complicated by diabetes. Diabetes has been around since the first
      century AD, in a perpetual state of coping and managing. It is time, it is long
      past time, to cure diabetes. But current models as to its cause are not equipping
      us to do so.

PMID- 15967590
TI  - Severe blood loss during spinal reconstructive procedures: the potential
      usefulness of topical hemostatic agents.
AB  - Complex spinal reconstructive procedures are invariably associated with excessive
      intraoperative blood loss that significantly increases the risk of severe
      perioperative complications. In some cases, excessive hemorrhage is equivalent to
      estimated total blood volume. Unfortunately, widely exposed bony surfaces are not
      amenable to standard hemostatic maneuvers utilized during soft tissue surgery.
      This article evaluates the clinical effectiveness of several approaches to blood
      management in this setting, and hypothesizes that underappreciated topical
      hemostatic agents may provide benefit by reducing the need for autologous
      predonation, banked donor blood or antifibrinolytic agents. Topical agents
      combining collagen, thrombin and fibrin have demonstrated initial promise by
      inducing platelet aggregation and initiating the clotting cascade when applied
      directly to bleeding bony sites. Clinical studies are clearly warranted.

PMID- 15967591
TI  - Antimicrobial flavonoids from the stem bark of Erythrina burttii.
AB  - The chloroform extract of the stem bark of Erythrina burttii showed antifungal
      and antibacterial activities using the disk diffusion method. Flavonoids were
      identified as the active principles. Activities were observed against fungi and
      Gram(+) bacteria, but the Gram(-) bacteria Escherichia coli was resistant.

PMID- 15967592
TI  - Antioxidant activity of isocytisoside and extracts of Aquilegia vulgaris.
AB  - Two extracts (ethyl acetate and ethanol) and isocytisoside obtained from
      Aquilegia vulgaris were tested for their antioxidant and free radical scavenging
      activity in vitro. Inhibition both non-enzymatic (IC50: 150-219 microg/ml) and
      enzymatic (IC50: 23-60 microg/ml) microsomal lipid peroxidation was observed, the
      extracts being more active than isocytisoside. The substances tested appeared to
      be weak hydroxyl radical scavengers, showed very low TEAC values and moderate
      iron chelation ability. However, all preparations at the concentration 25
      microg/ml inhibited superoxide anion formation at the range 47-68%. Despite of
      the lack of a potent free radical scavenging ability the substances tested
      demonstrated significant antioxidant activity. Relationship between this
      parameter and the content of phenolic groups was noticed.

PMID- 15967593
TI  - Essential oils of commonly used plants as inhibitors of peroxynitrite-induced
      tyrosine nitration.
AB  - The essential oils obtained from fifteen relevant and commonly used plants
      belonging to Cruciferae, Lamiaceae, Lauraceae, Apiaceae, and Zingiberaceae were
      screened using an in vitro model of peroxynitrite-induced tyrosine nitration.
      Almost complete inhibition of 3-nitrotyrosine formation (91% at 300 microg/ml)
      was achieved only with the essential oil obtained from the leaves of Laurus
      nobilis. 1,8-Cineol, accounting for a 50% of this essential oil, which resulted
      as inactive in this model, thus evidencing a major role for the minor volatile
      compounds present in the leaves.

PMID- 15967594
TI  - [An other research for saving research].

PMID- 15967595
TI  - Deficits in response inhibition associated with chronic methamphetamine abuse.
AB  - Chronic methamphetamine (MA) abuse is associated with cerebral deficits,
      involving frontal/basal-ganglia regions that are important for inhibitory
      control. We used the Stop-Signal Task to measure response inhibition in 11 MA
      abusers (5-7 days abstinent) and two groups of control subjects who did not use
      MA (14 tobacco smokers and 29 non-smokers). Stop-signal reaction time (SSRT),
      which indicates the latency to inhibit an initiated motor response, was
      significantly longer for MA abusers than for either control group (p's<.01). In
      contrast, the MA abusers did not differ from either group on Go trial reaction
      time (RT) or number of discrimination errors, which reflect motor speed and
      decision-processes, respectively. MA abuse in this study was therefore associated
      with a specific deficit in inhibiting a pre-potent response. Future research
      could examine whether SSRT is different for MA abusers who respond to treatment
      compared to those who do not. If such differences are established then response
      inhibition may serve as a marker for investigating MA abuse in basic science and
      clinical trials.

PMID- 15967596
TI  - Influence of inhalation anesthesia assessed by comprehensive gene expression
      profiling.
AB  - Although general anesthesia is routinely used as an essential surgical procedure
      and its harmlessness has been evaluated and endorsed by clinical outcomes, little
      is known about its comprehensive influence that is not reflected in mortality and
      morbidity. In this paper, we have shown that inhalation anesthesia affected the
      expression of <1.5% of >10,000 genes, by analyzing the expression profiles for
      multiple organs of rats anesthetized with sevoflurane. The small number of
      transcripts affected by the inhalation anesthesia comprised those specific to
      single and common in multiple organs. The former included genes mainly associated
      with drug metabolism in the liver and influenced by agents such as amphetamine in
      the brain. The latter contained multiple circadian genes. In the brain, we failed
      to detect the alteration of the clock gene expression with the exception of Per2,
      assuming that anesthesia perturbs circadian rhythms. Our findings provide the
      first assessment for the influence of inhalation anesthesia by approaches of
      experimental biology and genome science.

PMID- 15967597
TI  - Interaction between Rtg2p and Mks1p in the regulation of the RTG pathway of
      Saccharomyces cerevisiae.
AB  - Retrograde signaling mediates nuclear gene expression in response to changes in
      the functional state of mitochondria. In budding yeast, retrograde signaling,
      also termed the RTG pathway, relies on the heterodimeric, basic helix-loop-helix
      zipper transcription factors, Rtg1p and Rtg3p, for the activation of target gene
      expression. Activation of the RTG pathway leads to partial dephosphorylation of
      Rtg3p and its translocation, together with Rtg1p, from the cytoplasm to the
      nucleus. These processes depend on a positive regulatory factor, Rtg2p, a novel
      protein with a ATP binding domain similar to that of the Hsp70/actin/sugar kinase
      superfamily. Four negative regulatory factors, Lst8p, Mks1p, and two redundant 14
      3-3 proteins, Bmh1/2p, function between Rtg2p and Rtg1/3p. Alternative
      interaction between Mks1p and Rtg2p or Bmh1/2p provides a means for regulation of
      the RTG pathway. When the RTG pathway is on, Mks1p is inactivated by its
      association with Rtg2p; and when the RTG pathway is off, Mks1p dissociates from
      Rtg2p and forms a complex with Bmh1/2p, which is the negative regulatory form of
      Mks1p. Here we show that Rtg2p and Mks1p can interact in the absence of other
      factors, and is thereby the minimal binary switch for regulation of the RTG
      pathway. Gel filtration experiments indicate that both Rtg2p and Mks1p exist in
      high molecular weight complexes. In response to changes in the activity of the
      RTG pathway, both Rtg2p and Mks1p shift to different sized high molecular weight
      complexes. Together, our data suggest that dynamic association between Mks1p and
      Rtg2p in high molecular weight complexes provides a means to regulate the RTG
      pathway.

PMID- 15967598
TI  - Structure and transcription promoter activity of mouse flap endonuclease 1 gene:
      alternative splicing and bidirectional promoter.
AB  - Flap endonuclease 1 (FEN1) is a structure-specific nuclease involved in DNA
      replication and repair. The mouse Fen1 gene, which has two exons, is located
      immediately adjacent to the gene corresponding to full-length cDNA of Riken
      1810006K21 (1810006K21Rik) in a head-to-head orientation. Transcription
      initiation sites of each gene are 274 bp apart in the mouse genome. The spacer
      sequence between the bidirectional genes contains a CpG island, but lacks the
      typical TATA box. In the present study, transcription of the mFen1 gene was
      started from two initiation sites, and the first noncoding exon was spliced to
      the second exon using two different splicing donor sites, producing 3 kinds of
      mFen1 transcripts. A 594-bp fragment between the mFen1 and 1810006K21Rik genes,
      which contains two conserved sequence blocks (CSB) between mouse and human
      sequence, functions as a bidirectional promoter. The multiple cis-elements,
      including an Ets-binding site and E-box in the CSB, are involved in activation or
      repression of transcription in both directions. Interestingly, the E-box
      activates mFen1 transcription and simultaneously represses promoter activity in
      the opposite direction. Mutation of either splicing donor site of the mFen1 gene
      produced limiting alternative splicing products, but did not affect luciferase
      activity. In contrast, the splicing-defective mutation produced by disruption of
      the acceptor site completely lacked luciferase activity, indicating that the
      splicing has a significant effect on production of luciferase protein by
      shortening the 5'-untranslated region of the mRNA.

PMID- 15967600
TI  - Ribotyping of Streptococcus uberis from a dairy's environment, bovine feces and
      milk.
AB  - Streptococcus uberis is a major cause of bovine mastitis and infections commonly
      result from environmental exposure to the pathogen. To identify specific sources
      of mastitis-causing S. uberis strains, samples were collected monthly from the
      environment and feces of dry cows in a grazing herd. Environmental and fecal
      strains of S. uberis were compared to those found in milk. S. uberis was detected
      in 63% of 94 environmental samples, including water, soil, plant matter, bedding
      material, flies, and hay, in 23% of 107 fecal samples, and in 4% of 787 milk
      samples. Automated PvuII ribotyping revealed 48 ribotypes among 266 isolates. Per
      sample, up to five ribotypes were detected. The distribution of ribotypes did not
      differ significantly among environmental, fecal and milk samples. Specific
      environmental sources or strains of udder-pathogenic S. uberis were not
      identified. Fecal shedding was not persistent and did not differ between dry-off
      and calving. The proportion of fecal samples containing S. uberis was highest
      during the summer grazing season. S. uberis was common in farm soil (31 of 35
      samples) but not in non-farm soil (0 of 11 samples). We hypothesize that fecal
      shedding of S. uberis may play a role in maintenance of S. uberis populations in
      the dairy ecosystem.

PMID- 15967599
TI  - Characterization of Salmonella enterica serovar Typhimurium strains of veterinary
      origin by molecular typing methods.
AB  - Twenty-eight strains of Salmonella enterica serovar Typhimurium were
      characterized by three PCR-based methods. Ten strains harbored type I integrons
      and two different integron profiles were detected. Typing by amplified fragment
      length polymorphism (AFLP) resulted in observation of 10 profiles that differed
      by one to six bands. Salmonella strains were screened for presence of phage genes
      using a PCR-phage typing; five genes from P22 phage and genes encoding putative
      virulence factors from phages Gifsy-1, Gifsy-2 and Fels-1 were selected for
      testing. This set of genes was sufficient for dividing the strains into eight
      different PCR-phage profiles. Similar grouping of strains was observed in case of
      all the employed DNA techniques and they corresponded well with the phage type
      and antimicrobial resistance of the strains. The highest discriminating power was
      achieved with use of the AFLP, yet the detection of integrons and PCR-phage
      typing also proved to be valuable in typing the S. Typhimurium strains.

PMID- 15967601
TI  - Relationship between progesterone concentrations in milk and blood and time of
      ovulation in dairy cattle.
AB  - The objective of this study was to investigate whether monitoring progesterone
      concentrations in milk and blood plasma can be used to predict time of ovulation
      in dairy cattle. Whole milk was sampled twice daily and blood samples were
      collected once a day before the morning milking. Ovulation was assessed by trans
      rectal ultrasonography at 4h intervals beginning from the end of estrus. For a
      parameter to be useful as predictor for time of ovulation, it should be precise
      (i.e. variation between animals should not exceed 12h). In milk, progesterone
      concentration dropped <15 ng/ml at 97.7+/-17.8h (range: 54-126 h) before
      ovulation, to <5 ng/ml at 79.7+/-11.2h (range: 54-98) before ovulation to decline
      further to <2n g/ml at 70.7+/-16.8h (range: 38-90 h) before ovulation (n=20). In
      plasma, progesterone concentration dropped to <4ng/ml 90.5+/-19.6h (range: 66-138
      h) before ovulation and to <2 ng/ml at 75.0+/-12.2 h (range: 50-98) before
      ovulation. These intervals were not influenced by parity, milk production or days
      in milk. In conclusion, monitoring of progesterone alone is not sufficient to
      predict ovulation because of the large variation in timing of decrease of
      progesterone concentrations relative to ovulation between animals. At best the
      range is about 2 days.

PMID- 15967602
TI  - Supplementation of dextrose to the diet during the weaning to estrus interval
      affects subsequent variation in within-litter piglet birth weight.
AB  - Effects of supplementation of dextrose to the diet of sows during the weaning-to
      estrus interval (WEI) on subsequent litter size and within-litter variation were
      investigated. After weaning, 223 sows (first to fifth parity) were fed 3.5 kg/d.
      Half of the sows additionally received 150 g of dextrose per day as topdressing
      on the feed. WEI and estrus duration were determined as well as subsequent
      pregnancy rate and litter size. Piglets were weighed individually at birth and at
      weaning (day 26.4; S.D.: 2.5). Supplementation of dextrose to the diet during the
      WEI did not affect WEI (106 h), pregnancy rate (88.2%), farrowing rate (84.2%),
      subsequent litter size (total born: 13.70), or birth weight (1599 g). The within
      litter variation in birth weight was lower in sows on the dextrose treatment (CV:
      17.5% versus 21.2% for the dextrose and control group, respectively, P=0.03).
      From this experiment, we concluded that addition of dextrose during the weaning
      to estrus interval did not increase litter size, but seems to affect the
      uniformity in birth weight of the litter.

PMID- 15967603
TI  - Background factors influencing somatic and psychological symptoms in middle-age
      women with different hormonal status. A population-based study of Swedish women.
AB  - OBJECTIVE: To analyse the influence of socio-demographic characteristics and
      environmental factors on self-reported somatic and psychological symptoms among
      middle-aged Swedish women. METHODS: A total of 6917 women living in the Lund area
      of southern Sweden were participates of this study. They completed a generic
      questionnaire pertaining to socio-demographic characteristics, lifestyle factors
      and current health related problems. According to hormonal status, the
      participants were subdivided into three groups, i.e. premenopause, postmenopause
      and peri- or postmenopausal women with hormone replacement therapy (HRT).
      RESULTS: By using multiple logistic regression models, a high risk for somatic
      symptoms was independently associated with unemployment, no exercise, unmarried,
      high body weight and diseases affecting the cardiovascular system as well as a
      history of cancer. Psychological symptoms were independently associated with
      higher educational level, unemployment, no exercise, unmarried, heavy smoking
      habits (> or =15 cig/day), weight gain and a history of cancer. In addition, the
      background factors seemed to have less impact on symptoms among women who used
      HRT. CONCLUSION: Socio-demographic characteristics, lifestyle factors and
      concurrent health problems appear to have influences on the frequency and the
      number of somatic and psychological symptoms in middle-age women. Hormone
      replacement therapy seems to be able to counteract negative impacts caused by un
      healthy lifestyle and other health problems.

PMID- 15967604
TI  - Comparing raloxifene with continuous combined estrogen-progestin therapy in
      postmenopausal women: Review of Euralox 1.
AB  - OBJECTIVES: To review the main findings of the Euralox 1 study - a multicentre,
      randomised, double-blind study conducted in 1008 healthy postmenopausal women
      allocated to raloxifene (n = 495) or continuous combined estrogen-progestin
      therapy (ccEPT; n = 513) for 6 months -- and provide an overview of the risks and
      benefits of raloxifene and ccEPT. METHODS: A review is provided of previously
      published findings on uterine safety (bleeding rates and changes in endometrial
      thickness and uterine volume), gynaecological adjudication, cardiovascular risk
      (lipids, fibrinogen), adverse events, compliance, treatment satisfaction and
      quality of life. New data on biochemical markers of bone turnover (serum N
      telopeptides and C-terminal telopeptides of type I collagen; NTX and CTX)
      assessed before and after 6 months' treatment are presented. RESULTS: Raloxifene
      caused less uterine bleeding than ccEPT and, unlike ccEPT, did not alter
      endometrial thickness or uterine volume. Serum CTX and NTX levels were reduced in
      both treatment groups, but the reduction was significantly greater with ccEPT.
      The two treatments had differential effects on lipids and fibrinogen levels;
      raloxifene had more favourable effects on serum HDL, the LDL/HDL ratio, and
      plasma fibrinogen. Raloxifene was associated with fewer adverse events or
      discontinuations, and this was associated with higher treatment satisfaction and
      better self-reported compliance. CONCLUSIONS: The clinical risk-benefit profile
      of raloxifene derived from the intermediate endpoints of this study suggests that
      it may be a better alternative to ccEPT for preventing long-term postmenopausal
      health risks in healthy postmenopausal women who are not suffering from vasomotor
      symptoms.

PMID- 15967605
TI  - Controlled release of furosemide from the ethylene-vinyl acetate matrix.
AB  - The ethylene-vinyl acetate (EVA) matrix containing furosemide was prepared by the
      casting method and the release patterns were observed. The solubility of
      furosemide was determined as a function of volume fraction of polyethylene glycol
      400. The release of drug from the matrix was studied as a function of temperature
      and drug concentration. Plasticizers such as the citrates and the phthalates were
      added for preparing the membrane to increase the flexibility of the EVA matrix.
      The solubility of furosemide was the highest when the concentration of PEG 400
      was 40% (v/v). The release rate of drug from the EVA matrix increased with
      increasing temperature and drug loading doses. A linear relationship was found
      between the release rate and the square root of the loading dose. The activation
      energy (Ea), which was measured from the slope of the logP versus 1000/T plots,
      was 12.33 kcal/mol for the 0.5% loading dose, and 11.58 kcal/mol for the 1.0%
      loading dose, and 11.00 kcal/mol for the 1.5% loading dose. Among the
      plasticizers used such as the citrates and the phthalates groups, diethyl
      phthalate showed the best enhancing effects in drug release. In conclusion, the
      application of an EVA matrix containing a plasticizer might be useful in the
      development of a controlled drug delivery system.

PMID- 15967606
TI  - Effect of vitamin E TPGS on immune response to nasally delivered diphtheria
      toxoid loaded poly(caprolactone) microparticles.
AB  - The nasal mucosa has many advantages as a potential site for drug and vaccine
      delivery. The present study has sought to exploit this route of delivery using
      microparticles composed of D-alpha-tocopheryl polyethylene glycol 1000 succinate
      (TPGS) as a matrix material blended with poly(caprolactone) for nasal
      immunisation with diphtheria toxoid. Particles were prepared by a double emulsion
      method, followed by spray drying and the effect of TPGS on size, zeta potential,
      loading and release of antigen was assessed. Particles composed of TPGS-PCL
      blends were spherical, smooth and monodisperse, displaying increasing yields
      after spray drying with increasing concentrations of TPGS. The immune response to
      diphtheria toxoid loaded PCL-TPGS microspheres after nasal administration was
      shown to be higher than that achieved using PCL microspheres alone. We conclude
      that TPGS shows significant potential as a novel adjuvant either alone or in
      combination with an appropriate delivery system.

PMID- 15967607
TI  - Cholesterol-bile salt vesicles as potential delivery vehicles for drug and
      vaccine delivery.
AB  - The aim of this study was to further investigate the interactions between
      cholesterol (CH) and mixed bile salts (BS) (sodium cholate and sodium
      deoxycholate) and their suitability for drug and vaccine delivery. Insulin was
      used as a model protein to assess the ability of CH:BS vesicles to entrap a
      therapeutically relevant macromolecule. The association of protein (FITC-insulin)
      with the CH:BS structure was confirmed with fluorescence microscopy, and the
      overall morphology of the vesicles was examined with atomic force microscopy
      (AFM). Results demonstrate that the nature of the vesicles formed between CH and
      BS is dependent not only on the concentration of BS but also on the increasing CH
      concentration leading to CH crystal formation.

PMID- 15967608
TI  - Controlling the gelation of aqueous micellar solutions of ethylene-oxide-based
      block copoly(oxyalkylene)s.
AB  - Micellar solutions of EmPnEm copolymers may be mobile at ambient temperature and
      form hard gels on warming to body temperature, whereas micellar solutions of
      EmSnEm copolymers do not show this effect (E denotes oxyethylene, P oxypropylene
      and S oxyphenylethylene, and subscripts m and n denote chain lengths). The aim of
      this study was to combine the desirable gelation characteristics of solutions of
      the EmPnEm copolymers with the greater solubilising capacities of solutions of
      the EmSnEm copolymers. Accordingly, the gelation characteristics in aqueous
      solution of binary mixtures of the triblock copolymer E62P39E62 (Pluronic F87)
      with E137S18E137, E82S9E82 or E76S5E76 were investigated by rheological
      techniques. We have shown that 50/50 wt.% mixtures of E62P39E62 with either
      E137S18E137 or E82S9E82 at a total copolymer concentration of approximately 30
      wt.% are fluids of low viscosity at temperature below 22-25 degrees C and gels of
      high elastic modulus at body temperature.The mixed systems have potential as
      vehicles for the controlled delivery of solubilised drug from gels formed in situ
      following subcutaneous injection of a low viscosity aqueous solution.

PMID- 15967609
TI  - Antibacterial triterpenes from Syzygium guineense (Myrtaceae).
AB  - Antibacterial bioassay-guided fractionation of Syzygium guineense leaf extracts
      afforded 10 triterpenes, namely betulinic acid 1, oleanolic acid 2, a mixture of
      2-hydroxyoleanolic acid 3a, 2-hydroxyursolic acid 3b, arjunolic acid 4a, asiatic
      acid 4b, a mixture of terminolic acid 5a, 6-hydroxyasiatic acid 5b, and a mixture
      of arjunolic acid 28-beta-glucopyranosyl ester 6a and the asiatic acid 28-beta
      glucopyranosyl ester 6b. Isolated compounds were submitted to an antibacterial
      assay system against gram-positive and -negative bacteria and human pathogen
      bacteria. Compounds 4a and 4b showed the most significant antibacterial activity
      against Escherichia coli, Bacillus subtilis and Shigella sonnei. The fraction 5a
      5b was the least active, whereas compounds 1, 2 and the mixtures of 3a-3b and 6a
      6b were inactive in the assays.

PMID- 15967610
TI  - Clematis mandshurica protected to apoptosis of rat chondrocytes.
AB  - OBJECTIVE: To investigate the effect of SKI 306X, a purified extract from the
      mixture of three herbs, i.e. Clematis mandshurica, Trichosanthes kirilowii and
      Prunella vulgaris, on apoptosis in chondrocytes. DESIGN: Rat chondrocyte cell
      line RCJ3.1C.18 cells were incubated with 1 microM staurosporin and SKI 306X or
      each of its components. Cell viability was determined by trypan blue exclusion
      assay. Induction of apoptosis was determined by nuclear condensation or
      fragmentation after Hoechst staining. Amount of apoptosis was quantified both by
      nuclear morphology and flow cytometry. Expression level of Bcl-2, and caspase-3
      and PARP activations were assayed by Western blot. RESULTS: SKI 306X
      significantly prevented staurosporin-induced apoptosis. Among its three
      components, only Clematis mandshurica significantly decreased the amount of
      staurosporin-induced apoptosis. Although the level of Bcl-2 expression was
      decreased after staurosporin treatment, it was sustained after the combination
      treatment with Clematis mandshurica. Whereas staurosporin induced the degradation
      of 32 kDa caspase-3 precursor and the production of 85-kDa cleavage products of
      PARP in a time-dependent fashion, Clematis mandshurica treatment prevented those
      manifestations. CONCLUSIONS: Pharmacological efficacy of SKI 306X protecting
      osteoarthritis in part may result from the inhibition of apoptosis in
      chondrocytes by Clematis mandshurica.

PMID- 15967611
TI  - Evidence of addiction by anesthesiologists as documented by hair analysis.
AB  - Chemical dependency is a disease that can affect all professions. Among the
      health care professionals, anesthesiologists represent a specific group. Numerous
      factors have been proposed to explain the high incidence of drug abuse among
      anesthesiologists. These include: easy access to potent drugs, particularly
      narcotics, highly addictive potential of agents with which they are in contact,
      and easy diversion of these agents since only small doses will initially provide
      an effect desired by the abuser. Opioids are the drugs of choice for
      anesthesiologists, and among them fentanyl and sufentanil are the most commonly
      used. Alcohol is mostly abused by older anesthesiologists. Propofol, ketamine,
      thiopental and midazolam are also abused. In fact, all but quaternary ammonium
      drugs can be observed. Signs and symptoms of addiction in the hospital workplace
      include: unusual changes in behavior, desire to work alone, refusal of lunch
      relief or breaks, volunteer for extra cases, call, come in early and leave late,
      frequent restroom breaks, weight loss and pale skin, malpractice, behind on
      charts .... Toxicological investigations are difficult, as the drugs of interest
      are difficult to test for. In most cases, half-lives of the compounds are short,
      and the circulating concentrations weak. It is, therefore, necessary to develop
      tandem mass spectrometry procedures to satisfy the criteria of identification and
      quantitation. In most cases, blood and/or urine analyses are not useful to
      document impairment, as these specimens are collected at inadequate moments. Hair
      analysis appears, therefore, as the unique choice to evidence chronic exposure.
      Depending the length of the hair shaft, it is possible to establish an historical
      record, associated to the pattern of drug use, considering a growth rate of about
      1cm/month. An original procedure was developed to test for fentanyl derivatives.
      After decontamination with methylene chloride, drugs are extracted from the hair
      by liquid/liquid extraction after incubation in pH 8.4 phosphate buffer. Fentanyl
      derivatives are analyzed by GC-MS/MS. The following cases are included in this
      paper: Case 1: 50-year-old anesthetist, positive for fentanyl (644 pg/mg); Case
      2: 42-year-old anesthetist, positive for fentanyl (101 pg/mg) and sufentanil (2
      pg/mg); Case 3: 40-year-old anesthetist, positive for codeine (210 pg/mg),
      alfentanil (30 pg/mg) and midazolam (160 pg/mg); Case 4: 46-year-old nurse, found
      dead, positive for alfentanil (2 pg/mg) and fentanyl (8 pg/mg). In these cases,
      the combination of an alternative specimen (hair) and hyphenated analytical
      techniques (tandem mass spectrometry) appears to be a pre-requisite.

PMID- 15967612
TI  - Application of lead isotope analysis in shooting incident investigations.
AB  - A study was conducted to examine the potential of the considerable variability of
      the lead isotope compositions in bullets (projectiles) and primers in shooting
      incident investigations. Multiple-collector inductively coupled plasma mass
      spectrometry (MC-ICP/MS) was used to analyze lead isotopic compositions in
      projectiles, cartridge cases, firearms discharge residues (FDR) in barrels of
      firearms and in the gunshot entries. .22 caliber plain lead and plated ammunition
      and 9 mm Luger full metal jacket (FMJ) ammunition were employed in shooting
      experiments using semiautomatic pistols. Cotton cloth served as the target
      material and two firing distances were tested; 1 cm (near contact) and 2 m
      distances. It was observed that various mechanical or chemical means of cleaning
      do not completely remove lead deposits ("lead memory") from barrels of firearms.
      Nonetheless, it was shown that analysis of lead isotopic composition may provide
      valuable evidence in investigating specific scenarios of shooting incidents. For
      instance in a shoot-out where several firearms and ammunition brands are
      involved, it may be feasible to point out which ammunition and/or firearm caused
      a particular gunshot entry if the ammunition brands involved (bullets and
      primers) differ considerably in their lead isotopic composition.

PMID- 15967613
TI  - Malignant myoepithelioma arising from recurrent pleomorphic adenoma of the soft
      palate.
AB  - Malignant myoepithelioma is a rare salivary gland neoplasm that can arise either
      de novo or within a pre-existing pleomorphic adenoma. We report a case of
      malignant myoepithelioma arising from a pleomorphic adenoma of the soft palate. A
      70-year-old woman presented in our department with a very large tumor of the soft
      palate. The patient had a history of a pleomorphic adenoma at the same location
      that was surgically removed 2 years ago. A second operation, with intraoral
      excision of the tumor was performed. Histological examination of the recurrence
      revealed a malignant spindle cell neoplasm with an infiltrative growth pattern
      and a high mitotic rate. Immunohistochemical investigation confirmed the
      diagnosis of a low-grade carcinoma of myoepithelial origin with free surgical
      margins. The patient remains free of disease for more than twelve months after
      the end of treatment.

PMID- 15967614
TI  - Brain MRI findings of older patients with Pallister-Killian syndrome.
AB  - Pallister-Killian syndrome (PKS) is a disorder caused by a mosaic tetrasomy of
      chromosome 12p, which manifests with dysmorphism, intellectual disabilities,
      auditory disturbance, and epilepsy. Here, we describe the findings of brain
      magnetic resonance (MR) imaging in two patients with PKS. One patient, a 43-year
      old man, showed multiple lesions with high signal intensity on T2-weighted image
      (WI) in the basal ganglia, and widespread T2 elongation in the periventricular
      white matter. The same signal change was also present in the pontine base. The
      other patient, a 37-year-old woman, showed T2-high lesions in the bilateral
      putamina and the parietal periventricular white matter. There was prominent
      atrophy of the cerebellum and brainstem in this latter case. Both cases showed
      cortical atrophy with frontal predominance, with accompanying dilatation of the
      lateral ventricles. Hypoplastic corpus callosum was also present in both cases.
      Cerebral atrophy with ventricular dilatation has been often described in PKS
      cases, but many of the MR findings in the present patients have never been
      reported. Such findings may appear with advancing age in PKS. Since 12p mosaicism
      is rarely detected in peripheral blood lymphocytes, examination of buccal mucosal
      cells with fluorescent in situ hybridization method is preferable for the
      diagnosis of PKS. Recognition of the characteristic features on cranial MR
      imaging, in addition to the characteristic facial appearance in adulthood, should
      prompt the correct diagnosis of adult PKS patients.

PMID- 15967615
TI  - Cerebrospinal fluid interleukin-6 levels in patients with West syndrome.
AB  - Elevated cytokine response has been reported in patients with epileptic seizures.
      The objective of this study was to investigate the possible role of interleukin-6
      (IL-6) in the pathogenesis of infantile spasms in West syndrome (WS). We measured
      IL-6 levels in cerebrospinal fluid (CSF) obtained from the newly diagnosed
      patients with WS. Twelve patients with WS (Group I) were classified as
      symptomatic WS (Group IA) in eight and as cryptogenic WS (Group IB) in four. The
      results were compared with control groups including patients with tonic-clonic
      seizures associated with two different kind of inflammation of central nervous
      system; Group IIA (infection): bacterial meningitis/encephalitis and Group IIB
      (trauma): post-traumatic seizures. There was no statistically significant
      difference between the mean values of CSF IL-6 levels in patients with WS (2.95
      +/- 2.31 pg/ml) and those of subgroups of WS (Group IA: 2.26 +/- 2.01 pg/ml and
      Group IB: 4.33 +/- 2.52 pg/ml). Both control groups had highly increased IL-6
      levels in CSF (Group IIA: 193.05 +/- 185.52 pg/ml and Group IIB: 112.74 +/-
      167.44 pg/ml) than those of the patients with WS. Elevated IL-6 response in
      patients with tonic-clonic seizures associated with inflammation of central
      nervous system might be due to the seizures themselves or related to the
      underling etiology (infection or trauma). However, no elevated IL-6 response was
      found in patients with infantile spasms.

PMID- 15967616
TI  - Psychopathology in children and adolescents with Tourette's syndrome: a
      controlled study.
AB  - OBJECTIVE: Few controlled studies have considered, in paediatric subjects,
      associations between Tourette's syndrome (TS) and psychiatric/behavioural
      disorders. We conducted a case-control study to verify the reproducibility of the
      few data published on this topic to date. METHOD: Clinicians' impression (i.e.
      structured interviews and usual history taking), standardized psychiatric and
      behavioural rating scales (CBCL, TAI, CDI, CRS-R:L, Y-GTSS, CY-BOCS) were used to
      investigate these associations in 17 youngsters with TS and in 17 age- and sex
      matched controls. RESULTS: The clinician's diagnoses revealed TS alone in 23.5%
      of the patients (4/17), TS plus attention-deficit/hyperactivity disorder (ADHD)
      in 11.8% (2/17), TS plus obsessive-compulsive disorder (OCD) in 41.2% (7/17), and
      TS plus ADHD and OCD in 23.5% (4/17). No control subject presented ADHD and/or
      OCD. These clinical findings were confirmed by Child Behaviour Check List (CBCL)
      results. The TS group, compared with the controls, recorded significantly higher
      CBCL scores in scales relating to the main comorbid conditions. No significant
      differences emerged on the Children's Depression Inventory or Test Anxiety
      Inventory. CONCLUSION: TS patients have a high prevalence of psychiatric and
      behavioural problems compared with controls. The CBCL is a rapid and useful
      screening-diagnostic instrument for highlighting the main psychiatric and
      behavioural problems in TS.

PMID- 15967617
TI  - Buspirone in Rett syndrome respiratory dysfunction.
AB  - This study details a case of Rett Syndrome where the patient's respiratory
      dysfunction was improved after buspirone was administered. Polygraphic studies in
      the waking state, before and after treatment with 5 mg of buspirone twice a day,
      were obtained. Breathing movements, oxygen saturation and end-tidal carbon were
      monitored. Average oxygen saturation increased from 86.9 to 91%, and the period
      of saturation below 90% was reduced by 42.2%. The oxygen saturation improvement
      observed in this case suggests that buspirone might be useful in treating
      respiratory dysfunction associated with Rett Syndrome. Controlled clinical trials
      are needed to provide more evidence.

PMID- 15967618
TI  - Mutation analysis of methyl-CpG binding protein family genes in autistic
      patients.
AB  - Methyl-CpG binding protein 2 gene (MECP2), the gene implicated in Rett syndrome,
      was also reported to be involved in mental retardation and autism. MECP2, MBD1,
      MBD2, MBD3, and MBD4 comprise a nuclear protein family sharing the methyl-CpG
      binding domain (MBD) and are related to transcriptional repression. In 65
      Japanese autistic patients, all the exons of each gene were screened for
      mutations by DHPLC, and the results were confirmed by direct sequencing. An R269C
      mutation that resulted in the addition of cysteine near a cysteine rich region
      was found in the MBD1 gene in one patient. This mutation was also detected in the
      patient's father with some phenotypes of autism and his normal sister, but not in
      151 controls. Two repeat length polymorphisms, (GGGGCC)2 to 3 and (GGC)4 to 5,
      were detected in MBD2, and several polymorphisms were detected in each gene.
      Although our findings could not confirm that the genes of this family are
      responsible for the etiology in the majority of autistic patients, the R269C
      mutation in the MBD1 gene may relate to autism. The potential association of the
      high-polymorphic gene variants with autism needs to be studied further.
      Furthermore, these polymorphisms are useful for linkage analysis.

PMID- 15967619
TI  - 'Benign focal epilepsy in infancy with vertex spikes and waves during sleep'.
      Delineation of the syndrome and recalling as 'benign infantile focal epilepsy
      with midline spikes and waves during sleep' (BIMSE).
AB  - PURPOSE: To better delineate the electroclinical features of infants who
      presented with focal seizures and typical midline sleep EEG abnormalities with a
      benign outcome. We discuss the significance of the typical EEG marker in non
      epileptic patients. METHODS: Patients were selected from a group of epileptic
      subjects with seizure onset less than 3 years we observed from 1st November 1990
      and 31st December 2003. Inclusion criteria were the presence of typical sleep EEG
      marker and focal seizures with benign outcome. Cases with less than 18 month
      follow-up period were excluded from this study. RESULTS: There were 19 patients
      (12 males, 7 females). Pre-, peri- and post-natal personal history was negative
      in all patients. Psychomotor development was normal, both before and after
      seizure onset. Neuroradiological investigations gave normal results. Seizure
      manifestations were typical, characterized by cyanosis, staring and rare
      lateralizing signs, of short duration. Age at onset was comprised between 4 and
      30 months. The typical EEG marker, a spike followed by a bell-shaped slow-wave,
      localized in the midline regions, was present in all subjects only during sleep.
      All had a favorable outcome and the overwhelming majority of the patients were
      not treated. CONCLUSIONS: Our patients have an homogeneous electroclinical
      picture to constitute a new epileptic syndrome not included in the ILAE
      classification. We propose to call it 'benign focal epilepsy in infancy with
      midline spikes and waves during sleep' (BIMSE).

PMID- 15967620
TI  - Magnetic resonance studies of brain lesions in patients with Kawasaki disease.
AB  - We evaluated brain lesions in patients with coronary arterial lesions (CAL) as a
      complication of Kawasaki disease (KD) by magnetic resonance imaging (MRI) and
      magnetic resonance angiography (MRA). Among 47 patients who underwent coronary
      angiography for the evaluation of CAL due to KD at Kyushu University Hospital
      from April 1996 to September 2004, 24 patients were evaluated prospectively by
      brain MRI and MRA 0.1-21.2 years after the onset of KD. Although most patients
      had irritability or lethargy, none of them had significant neurological symptoms
      or signs during the acute phase, except one who showed neck stiffness. In one
      patient with no apparent neurological symptoms out of the 24 patients, brain MRI
      and MRA revealed right cerebellar infarction and obliteration of the right
      posterior inferior cerebellar artery, respectively. These results revealed the
      presence of cerebrovascular lesion in one of the 24 KD patients with CAL and
      suggested the need to consider the possibility of brain lesions in severe cases
      of KD with or without neurological symptoms.

PMID- 15967621
TI  - Importance of T2*-weighted gradient-echo MRI for diagnosis of cortical vein
      thrombosis.
AB  - We examined six patients with isolated venous thrombosis (n = 2), or venous
      thrombosis combined with sinus thrombosis (n = 4) (CVT). The clinical symptoms
      were non-specific (acute cephalea, paresis, epileptic seizure, progressive speech
      disorder). All examinations were performed on a 1.5 T system (Magnetom Symphony,
      Siemens, Erlangen, Germany), maximum gradient field strength 30 mT/m, minimal
      gradient rise time 450 micros, according to the following protocol: Transverse T2
      weighted turbo spin-echo (TSE), fluid attenuated inversion recovery (FLAIR), T1
      weighted spin-echo (SE), before and after administration of contrast medium, T2*
      weighted conventional gradient-echo (GRE), T2*-weighted spin-echo echo planar
      imaging (SE EPI), both without and with diffusion weighting as well as two
      dimensional (2D) venous time-of-flight (TOF) MRA. The venous thromboses were best
      detectable in the T2*-weighted conventional GRE sequence in all patients. In two
      patients, the CVT was discernible only in this sequence. The sinus thrombosis was
      well discernible only in the T2*-weighted GRE sequence in only one case; in the
      remaining cases it was detectable only with difficulty. For these cases, other
      sequences such as SE, diffusion-weighted, or 2D-TOF-MRA sequence were superior.
      The T2*-weighted conventional GRE sequence was superior to the T2*-weighted SE
      EPI sequence in all patients. To sum up, it can be concluded, that T2*-weighted
      conventional GRE sequences are possibly the best method of detection of acute
      cortical vein thromboses. Therefore, it seems to be of benefit to integrate a T2*
      weighted conventional GRE sequence into the MR-protocol for the diagnosis of
      isolated cortical vein thrombosis.

PMID- 15967622
TI  - Acidity constants of cefetamet, cefotaxime and ceftriaxone; the effect of the
      substituent at C3 position.
AB  - Ionization constants of three cephalosporin antibiotics, cefetamet (CEF),
      cefotaxime (CFX) and ceftriaxone (CFTR) are determined using pH-potentiometric
      titrations at I=0.1 M (NaCl) and t=25 degrees C. Cefetamet and cefotaxime have
      three ionization groups: carboxylic, amide and aminothiazole. Besides those
      three, ceftriaxone possesses an hydroxytriazinone group as new and additional
      ionization center. In acid medium two overlapping acid-base processes are
      occurring with acidity constants being: pK1 2.93 (COOH) and pK2 3.07
      (aminothiazole) for cefetamet, and pK1 2.21 (COOH) and pK2 3.15 (aminothiazole)
      for cefotaxime. In the case of ceftriaxone the situation is even more
      complicated, three overlapping processes coexist with pK1 2.37 (COOH), pK2 3.03
      (aminothiazole) and pK3 4.21 (hydroxytriazinone). Protolysis of amide group is
      happening in the alkaline medium as completely separated process from those in
      acid medium. The acidity constants which correspond to amide group are pK3 10.65
      (CEF), pK3 10.87 (CFX) and pK4 10.74 (CFTR). The influence of the C3 substituent
      on the dissociation process of the neighboring ionization group, particularly
      carboxylic group, was considered. The differences in acidity of CEF, CFX and CFTR
      (pK1: 2.93, 2.21 and 2.37, respectively) are likely to be caused by the
      stereoelectronic properties of substituents in the beta-position to the
      carboxylic group due to the combined inductive, hyperconjugative and resonance
      effects.

PMID- 15967623
TI  - Determinants of adoption of cognitive behavioral interventions in a hospital
      setting: example of a minimal-contact smoking cessation intervention for
      cardiology wards.
AB  - OBJECTIVE: The aim of our study was to identify the psychological and
      organizational determinants of adopting a smoking cessation intervention in
      cardiology wards, using the Integrated Change Model (I-Change Model) as the
      theoretical basis. METHODS: A cross-sectional survey by means of questionnaires
      was conducted among the heads of all 121 cardiology wards in Dutch hospitals, of
      whom 77 (64%) responded. RESULTS: Adopters had a significantly lower level of
      formalization and more nurses working on the ward. Adopters also had a
      significantly more positive attitude towards working with the intervention,
      perceived more positive social influences from their direct environment and had
      higher self-efficacy. Psychological determinants explained adoption to a greater
      extent than organizational determinants did. CONCLUSION: It is very important to
      take psychological factors into account when studying the adoption of preventive
      innovations and developing diffusion strategies. PRACTICE IMPLICATIONS: Programs
      for dissemination of preventive innovations in a hospital setting should
      primarily focus on psychological characteristics like social influence and self
      efficacy.

PMID- 15967624
TI  - Preparing for aging: development, feasibility and preliminary results of an
      educational program for midlife and older based on proactive coping theory.
AB  - OBJECTIVES: This article describes the development, content, feasibility and
      first results of a short educational program for preparing for aging, based on
      the process model of proactive coping. The aim of the program is to increase
      proactive competencies and improve proactive orientations and behaviour. The
      program consists of four-weekly meetings with 8-10 participants and is given by
      trainers of about the same age as the participants. METHODS: Sixty-eight persons
      (M=61.4 years) participated in the program. Feasibility included attendance,
      participants evaluations of the meetings and the applicability of the used
      techniques. Proactive coping was measured as proactive orientation, behaviour and
      competencies. RESULTS: The program received positive evaluations, the attendance
      rate was very satisfying, and the applicability of the used techniques have been
      shown. Regarding the technique of mental simulation, improvements were suggested.
      We found gender differences concerning feasibility: women evaluated the program
      to be easier and reported to have profited more from mental simulation.
      Preliminary results of proximal outcome variables showed significant changes in
      proactive competencies, but no changes in proactive behaviour and proactive
      orientation. CONCLUSIONS: The educational program "In anticipation of the golden
      years" is a theoretical based minimal intervention which is highly feasible and
      effective in improving proactive competencies.

PMID- 15967625
TI  - Intercultural communication competence in family medicine: lessons from the
      field.
AB  - OBJECTIVE: To describe the challenges for immigrant patients and their physicians
      and their skills in intercultural communication (ICC). METHODS: We videotaped one
      clinical encounter for each of 24 psychologically distressed patients visiting
      their regular family physician. The physician and the patient, each separately,
      viewed the videotape of their clinical encounter and commented on important
      moments identified by the participant or the researchers. RESULTS: Patients
      and/or physicians lacked knowledge of the effects of culture on the doctor
      patient relationship and expressions of distress as well as the effects of
      immigrant-specific stress on health. Most subjects were motivated to have an
      interpersonal, rather than an intercultural encounter. Physicians and patients
      demonstrated the skills needed to achieve an interpersonal encounter. Some
      physicians and their patients achieved intercultural meetings as a result of
      their interpersonal interactions over a period of years. DISCUSSION: Lack of
      formal training partly explains why most participants demonstrated an elementary
      level of ICC. In addition, Identity Management Theory and Co-cultural Theory
      explain some of the barriers to ICC. PRACTICE IMPLICATIONS: Providing physicians
      with formal training in intercultural communication and empowerment training for
      patients is likely to improve the quality of care of immigrants.

PMID- 15967626
TI  - [Treatment of intracranial hypertension in patients suffering from severe
      subarachnoid haemorrhage].

PMID- 15967627
TI  - [Diagnosis in general hospital and immediate care of patients suffering from
      severe subarachnoid haemorrhage].

PMID- 15967628
TI  - [Perioperative management of asplenic patients].
AB  - OBJECTIVE: In 2003, asplenia had involved 250000 patients in France. These
      patients are at risk of severe infection, mostly with capsulated bacteria as
      pneumococci, meningococci and Haemophilus. The higher mortality and morbidity due
      to infection in asplenic patient led in June 2003 a French expert committee to
      propose preventive management based on vaccination and antibioprophylaxis. STUDY
      DESIGN: Update article. DATA SYNTHESIS: For vaccination, two vaccines against
      pneumococci are available. The first one, the antipolysaccharide (Pneumo 23) is
      recommended for adults. It is effective for the majority of the serotypes even if
      its efficacy can be variable. The second one a conjugated pneumococcal vaccine
      (Prenevar) is used for children under two years because it has higher activity on
      antibiotic resistant strains therefore increasing antibiotic prophylaxis
      efficiency. When splenectomy is required, vaccination against pneumococci,
      Haemophilus (b type) and C meningococci must be performed at least 15 days before
      surgery, in order to get better immune stimulation. In case of emergency,
      vaccines have to be administrated within 30 days after surgery.
      Antibioprophylaxis is based on cefazolin injection before splenectomy and by
      postoperative intravenous amoxicillin administration. As soon as oral intake is
      allowed, antibioprophylaxis is continued for at least two years in adults and
      five years in children. Both antibiotic and vaccination have been reported to
      reduce pneumococcus infections.

PMID- 15967629
TI  - Mycobacterial trehalose 6,6'-dimycolate preferentially induces type 1 helper T
      cell responses through signal transducer and activator of transcription 4
      protein.
AB  - Mycobacterium tuberculosis is an intracellular pathogen of tuberculosis and its
      pathogenicity is related to the ability to escape killing by ingested macrophages
      and induce delayed-type hypersensitivity (DTH). A major component of the cell
      wall of M. tuberculosis is trehalose 6,6'-dimycolate (TDM), which has been
      implicated as a pathogenetic factor. The expression of DTH and cell-mediated
      immunity is dependent on the macrophage-cytokine-type 1 helper T (Th1) lymphocyte
      axis. Cytokines, interleukin-12 (IL-12) and interferon-gamma (IFN-gamma), play a
      critical role in the process and IL-12-activated signal transducer and activator
      of transcription (STAT) 4 is required for the development of fully functional Th1
      cells. To clarify host responses to mycobacterial TDM, we have analyzed footpad
      reaction, histopathology and cytokine profile of experimental granulomatous
      lesions using STAT4-deficient mice. In the present study, we have demonstrated
      that mycobacterial TDM selectively induces the Th1 response through the STAT4
      signaling pathway, because mice lacking STAT4 protein significantly reduced to
      develop DTH, hypersensitivity granulomas, and Th1 cytokine responses, when
      compared to BALB/c mice. These results shed light on the molecular pathogenesis
      of mycobacterial disease. Taken together with previous studies, TDM is a
      pleiotropic molecule against the host and participates in the pathogenesis.

PMID- 15967630
TI  - Preschool children with mild to moderate traumatic brain injury: an exploration
      of immediate and post-acute morbidity.
AB  - This study explored premorbid, neurocognitive, behavioral, and familial factors
      in preschoolers, ages 3-6, who experienced a mild to moderate traumatic brain
      injury (TBI). Twenty-nine children with TBI, 33 children with mild to moderate
      injuries to other body regions, and 34 non-injured children participated in the
      study. Neuropsychological assessments and behavioral measures were administered
      at the time of hospitalization and 6 months later. In comparison to the non
      injury children, preschool-aged children with TBI had higher rates of premorbid
      behavior difficulties, lower premorbid cognitive functioning, and poorer
      development of pre-academic skills. In addition, parents of children with TBI
      reported greater situational issues and life stressors than parents of children
      in the non-injured group. Some neurocognitive recovery was evident in the TBI
      group, but no differences were recognized in behavioral and family measures at
      the 6-month follow-up. This study emphasizes the relative effects of premorbid
      characteristics in later practice of preschool children who sustain TBI.

PMID- 15967631
TI  - Social interactions alter proinflammatory cytokine gene expression and behavior
      following endotoxin administration.
AB  - Sick animals display a constellation of behaviors, including anhedonia, anorexia,
      and reduced social interactions. Acute infection eliminates female mating
      behavior, but fails to attenuate mating behavior in male rats. These results have
      been attributed to the different reproductive strategies and parental investment
      of the two sexes. Males putatively suppress the symptoms of infection in order to
      "deceive" females into mating. We sought to investigate the mechanisms
      responsible for this suppression. Adult male CD-1 mice were treated with
      lipopolysaccharide (LPS; a component of bacterial cell walls; 400 microg/kg),
      then paired 2 h later with a receptive female or juvenile male or remained
      isolated. Blood samples and brains of the males were collected 3 h post-LPS;
      hypothalamic interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNFalpha) gene
      expression was measured using RT-PCR. Contrary to our prediction, exposure to a
      female increased hypothalamic IL-1 and TNFalpha gene expression. LPS treatment
      significantly decreased testosterone and increased corticosterone secretions.
      Social interactions altered absolute corticosterone concentrations in saline
      injected animals only. In order to determine whether increased production of
      hypothalamic cytokines reflected increased severity of sickness responses, body
      temperature was monitored in a second group of mice implanted with telemetric
      transmitters. Body mass, food intake, and consumption of sweetened condensed milk
      (a highly favored food) were also monitored in these mice for 72 h post
      injection. LPS injections reduced milk intake, an effect that was modulated by
      social interactions; however, fever was unaltered relative to isolated animals.
      These results suggest that social interactions can adjust behavioral responses to
      infection although the ultimate cause of this adjustment remains unspecified.

PMID- 15967632
TI  - Human embryonic stem cells: genetic manipulation on the way to cardiac cell
      therapies.
AB  - Almost 7 years after their first derivation from human embryos, a pressing
      urgency to deliver the promises of therapies based on human embryonic stem cells
      (hESC) has arisen. Protocols have been developed to support long-term growth of
      undifferentiated cells and partially direct differentiation to specific cell
      lineages. The stage has almost been set for the next step: transplantation in
      animal models of human disease. Here, we review the state-of-the-art with respect
      to the transplantation of embryonic stem cell-derived heart cells in animals. One
      problem affecting progress in this area and functional analysis in vivo in
      general, is the availability of genetically marked hESC. There are only a few
      cell lines that express reporter genes ubiquitously, and none is associated with
      particular lineages; a major hurdle has been the resistance of hESC to
      established infection and chemical transfection methodologies to introduce
      ectopic genes. The methods that have been successful are reviewed. We also
      describe the processes for generating a new, genetically-modified hESC line that
      constitutively expresses GFP as well as some of its characteristics, including
      its ability to form cardiomyocytes with electrophysiological properties of
      ventricular-like cells.

PMID- 15967633
TI  - The contribution of new findings and ideas to the old principles of teratology.
AB  - Although the last generally accepted concept of principles of teratology was
      issued more than 30 years ago, the cause of less than 50% of all congenital
      anomalies is known and no substantial change in their incidence has been observed
      worldwide. In the meantime, powerful techniques of molecular biology as well as
      many sophisticated preventive measures have been introduced with marginal effects
      on the overall birth defects numbers. In this paper, we follow the history of
      basic concepts of teratology starting with Isidore Geoffroy Saint-Hilaire and
      Dareste, followed in the 20th century by James Wilson. Since that time no bright
      and completely new idea, which would deserve the name principle, has emerged. The
      advanced molecular studies support the long-existing principles and disclose the
      great variability of individuals and their responses to adverse exposures. In
      this way, the future of teratology counseling may be seen in a deep analysis of
      any individual case.

PMID- 15967634
TI  - Teratogenic effects of diphenyl diselenide in Wistar rats.
AB  - Diphenyl diselenide is an organoselenium compound with potential therapeutic use.
      The present study evaluates the effects of single maternal subcutaneous injection
      of 50 and 100mg/kg diphenyl diselenide [(PhSe)2] at gestational days (GD) 6, 10
      or 17 in Wistar rats. The highest dose of (PhSe2 was also administered at GD 7
      12. External and internal fetal soft-tissue examination was performed at GD 20.
      No mortality was observed in fetuses or dams at any (PhSe)2 treatment group.
      Neither did exposure to (PhSe)2 cause significant changes to fetal body weight,
      organ weight, or fetal size when administered at GD 6-8, 10-12 or 17. Exposure to
      100mg/kg (PhSe)2 at GD 9 produced significant changes in fetal biometry (crown
      rump (CR) length) and body weight. No significant increase in the proportion of
      fetuses with external visible abnormalities was observed in groups exposed to
      (PhSe)2. Skeletal anomalies were observed in fetuses in the GD 9-11 treatment
      groups and included incomplete ossification of cranial bones, misshapen and
      incomplete ossification of sternebrae, reduced sternebrae number, wavy and extra
      ribs, incomplete ossification of fore and hindpaw bones and incomplete
      ossification of sacral and caudal bones. We conclude that maternal administration
      of (PhSe)2 during GD 7-12 led to increased incidences of these skeletal
      variations or anomalies, but did not cause externally visible malformations in
      rat fetuses.

PMID- 15967635
TI  - Analysis of the three common mutations in the CARD15 gene (R702W, G908R and
      1007fs) in South African colored patients with inflammatory bowel disease.
AB  - The caspase recruitment domain-containing protein 15 gene (CARD15) was recently
      identified as an important susceptibility gene for Crohn's disease (CD). The
      purpose of this study was to assess the likelihood that the three most common
      CARD15 mutations, R702W, G908R and 1007fs, contribute to inflammatory bowel
      disease (IBD) susceptibility in the South African colored population. The study
      cohort included 76 IBD patients, 41 with CD and 35 with ulcerative colitis (UC),
      and 100 population-matched controls. Mutations R702W, G908R and 1007fs were
      present at relatively low frequencies (<20%) in our study population. No
      statistically significant differences were furthermore, observed for these
      mutations between UC and CD patients or when compared with normal control
      individuals. Two additional mutations were identified, one novel (A661P) and one
      previously described (A725G), with the latter being identified in 4 of 35 (11%)
      UC patients. Statistically significant differences were obtained between UC and
      control individuals when comparing both allele (p<0.004, chi2 with Yates'
      correction=8.01) and genotype frequencies (p<0.004, chi2 with Yates'
      correction=8.14) for the A725G mutation, suggesting a possible role for this
      variant in disease expression.

PMID- 15967636
TI  - Phonological reading skills acquisition by children with mental retardation.
AB  - Twenty children with mental retardation (MR), age 7-12, completed a phonological
      reading skills program over approximately 10 weeks. As a result of the
      instruction, they were better able to sound out learned and transfer words
      compared to a control group matched on age, IQ, nonword reading, language
      comprehension, and phonemic awareness. Final sounding out was predicted by
      beginning reading skill in both groups, by phonemic awareness and articulation
      speed in the control group only, and by general language ability in the
      instruction group only. Neither IQ nor verbal working memory correlated
      significantly with final sounding out ability in either group. It is suggested
      that the instruction succeeded in compensating for weaknesses in phonemic
      awareness and speech articulation, but favored those who had better language
      skills.

PMID- 15967637
TI  - Constitutive activation of STAT proteins in the HDLM-2 and L540 Hodgkin lymphoma
      derived cell lines supports cell survival.
AB  - Survival and proliferation of Hodgkin lymphoma (HL) cells are influenced by many
      cytokines produced by different cell types in the lymph node microenvironment.
      STAT, family of transcription factors, are key mediators of cytokine signaling
      and their perturbation contributes to various human diseases. Electrophoretic
      mobility shift and phosphoprotein immunoblotting analyses were used to study STAT
      activation in HL cell lines. We thus observed high levels of constitutively
      activated STAT1, 3, 5 and 6 in HDLM-2 and L540 cells, which could be correlated
      with JAK kinase activation. In contrast KM-H2 cells did not display STAT
      activation. Preventing constitutive STAT activation by specific JAK kinases
      inhibitors induced apoptosis of HL cell lines and was associated with a strong
      decrease in the expression of the anti-apoptotic genes IAP-1, IAP-2, Bcl-xL, Bfl1
      and Traf1. Silencing of JAKs by specific siRNAs also induced apoptosis of HL
      cells. Altogether, these results suggest that aberrant STAT activation in Hodgkin
      cells may promote cell survival and as a consequence facilitate oncogenic
      transformation.

PMID- 15967638
TI  - The Sentinel Project: an update on the prevalence of antimicrobial resistance in
      community-acquired respiratory Streptococcus pneumoniae and Haemophilus spp. in
      Italy.
AB  - A total of 460 Streptococcus pneumoniae and Haemophilus spp. collected from
      respiratory infections during 2000 was tested for their susceptibility to 15
      selected antibiotics. Overall, penicillin resistance among pneumococci was 10.5%,
      while lack of susceptibility to macrolides, co-trimoxazole, tetracycline and
      chloramphenicol reached 35.2%, 26.2%, 22.6% and 6.0%, respectively.
      Amoxicillin/clavulanic acid and levofloxacin were the most potent compounds (100%
      and 99.9% susceptible strains, respectively). Among isolates of Haemophilus
      influenzae and Haemophilus parainfluenzae, beta-lactamase production (12.5% and
      10%, respectively), and co-trimoxazole (19.9% and 40.0%) and clarithromycin
      (11.2% and 40.0%) resistance were the prevalent threats. This study confirms the
      trend observed in Italy since 1992: macrolide resistance among respiratory
      microorganisms is increasing, while several drugs including
      amoxicillin/clavulanic acid, third generation injectable cephalosporins and
      fluoroquinolones remain active on the great majority of these pathogens.

PMID- 15967639
TI  - Effects of probiotics on the composition of the intestinal microbiota following
      antibiotic therapy.
AB  - The effects of probiotic supplementation on the intestinal re-growth microbiota
      following antibiotic therapy were studied in a double-blind placebo-controlled
      study. In the placebo group, numbers of facultative anaerobes and enterobacteria
      increased significantly, and at day 35 the numbers were significantly higher in
      the placebo group than in the active group; in the active group, the numbers of
      bacteroides increased significantly. Although the numbers of enterococci in both
      groups did not change, in the placebo group the number of patients harbouring
      antibiotic-resistant enterococci post therapy increased significantly. There was
      no change in the incidence rate of antibiotic resistance among the patients in
      the probiotic group.

PMID- 15967640
TI  - Trends in linezolid susceptibility patterns: report from the 2002-2003 worldwide
      Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program.
AB  - Linezolid is an important oxazolidinone antimicrobial for the treatment of
      infections caused by Gram-positive cocci, especially vancomycin-resistant
      enterococci and oxacillin-resistant Staphylococcus aureus (ORSA). Since its
      introduction, however, ribosomal mutations have been detected that produce
      resistance; thus, longitudinal surveillance remains necessary to monitor for
      emerging resistance in all geographic areas of oxazolidinone use. The 2003 Zyvox
      Annual Appraisal of Potency and Spectrum (ZAAPS) Program compared linezolid
      minimum inhibitory concentration (MIC) results with 13-15 comparator
      antimicrobial agents (8089 isolates) and also with results from an earlier
      surveillance period (2002). Sampling institutions in the United States of America
      (USA), Canada, Europe (seven nations), South America (three nations) and the Asia
      Pacific (three nations) referred 200 Gram-positive cocci to the central
      laboratory for MIC processing and identification confirmation. Linezolid
      resistance (MIC > or = 8 mg/L) was established by alternative susceptibility
      testing methods as well as by ribosomal target characterisation. Concurrent drug
      use data were collected. Linezolid activity against the six major organism groups
      did not vary between years or geographic areas. In contrast, penicillin
      resistance increased 2% in Streptococcus pneumoniae; macrolide resistance was
      stable among beta-haemolytic streptococci (19-21%), but increased in S.
      pneumoniae (+2%); ORSA rates increased 4%; and vancomycin resistance in
      enterococci was present, but varied markedly by region. Non-clonal linezolid
      resistant isolates were detected, each having the same G2576U 23S rRNA target
      mutation. Furthermore, the first linezolid-resistant, non-USA isolate (S. aureus
      in Greece) was observed, apparently related to linezolid use. In 2003, near
      complete activity for linezolid against Gram-positive isolates was again
      documented (99.93% susceptible) in the ZAAPS Program. Rare linezolid-resistant
      isolates were identified among enterococci, limited to USA strains. Limited
      correlations of linezolid resistance to drug use continues, with an average
      consumption rate of 0.63DDD/100 patient days (a 50% increase since 2002), and
      indicates the important role of hospital hygiene practice in preventing the
      dissemination of oxazolidinone resistances, should they be detected.

PMID- 15967641
TI  - Basal ganglia calcification and psychosis in 22q11.2 deletion syndrome.
AB  - Intracerebral calcifications are a facultative symptom of hypoparathyreoidism in
      22q11.2 deletion syndrome (22qDS). We describe a patient with 22qDS, basal
      ganglia calcification (BGC) and psychotic symptoms and discuss the etiological
      connection of BGC with psychiatric symptoms. Future work needs to determine the
      prevalence of BGC in 22qDS and psychiatric disorders.

PMID- 15967642
TI  - Measuring quality of life in first-episode psychosis.
AB  - Quality of life (QoL) measures are increasingly recognized as necessary parts of
      outcome assessments in psychosis. The present paper is a comprehensive study of
      patients with first-episode psychosis where QoL is measured by the commonly used
      Lehman Quality of Life Interview (L-QoLI). The aim is to examine if the L-QoLI
      maintain its original structure when used in a group of patients with first
      episode psychosis, and to investigate what determines global subjective QoL with
      a specific emphasis on premorbid adjustment, duration of untreated psychosis
      (DUP) and clinical symptoms. The study indicates that the psychometric properties
      of the L-QoLI do not change significantly when used in first-episode samples. The
      patients report subjective and objective QoL in the fair to good range, with only
      a moderate association between the objective and subjective measures. Poor global
      satisfaction is predicted by being single, abusing drugs, being depressed, having
      a diagnosis of psychotic affective disorder, having poor premorbid social
      adjustment and DUP over 10 weeks. The study supports the notion that patients
      with first-episode psychosis construct QoL in the same way as other groups, and
      that longer durations of compromised function at this stage produces poor
      satisfaction with life rather than a downward readjustment of expectations.

PMID- 15967643
TI  - Social needs of people with severe functional impairments living in a rural
      district in Sweden. A population-based study.

PMID- 15967644
TI  - Do personality disorders predict negative treatment outcome in obsessive
      compulsive disorders? A prospective 6-month follow-up study.
AB  - BACKGROUND: Comorbid personality disorders (PDs) are discussed as risk factors
      for a negative treatment outcome in obsessive-compulsive disorder (OCD). However,
      studies published so far have produced conflicting results. The present study
      examined whether PDs affect treatment outcome in patients with OCD. METHOD: The
      treatment sample consisted of 55 patients with OCD who were consecutively
      referred to a Behaviour Therapy Unit for an in-patient or day-clinic treatment.
      Treatment consisted of an individualised and multimodal cognitive behaviour
      therapy (CBT, with or without antidepressive medication). Measurements were taken
      prior and after treatment and 6-month after admission. RESULTS: A large
      percentage of patients benefited from treatment irrespective of the presence of a
      PD and were able to maintain their improvement at follow-up. Duration of
      treatment was not prolonged in OCD patients with concomitant Axis II disorders.
      However, some specific personality traits (schizotypal, passive-aggressive) were
      baseline determinants for later treatment failure at trend level. CONCLUSIONS:
      Results are encouraging for therapists working with patients co-diagnosed with
      Axis II disorders since these patients are not necessarily non-responders. The
      results stress the importance of a specifically tailored treatment approach based
      on an individual case formulation in OCD patients with complex symptomatology and
      comorbid Axis II disorders.

PMID- 15967645
TI  - Lysosomal leukocyte beta-D-glucuronidase during enzyme replacement therapy in
      Fabry disease.
AB  - OBJECTIVE: Fabry disease results from a deficiency in the activity of alpha-d
      galactosidase A and subsequent accumulation of neutral glycosphingolipids in
      lysosomes. This study investigated whether lysosomal enzymes can indicate
      biochemical changes in the lysosomal apparatus induced by enzyme replacement
      therapy (ERT). DESIGN AND METHODS: Eight patients were monitored by clinical and
      biochemical tests and several lysosomal glycohydrolases were measured in plasma
      and leucocytes. RESULTS: Before starting ERT, beta-d-glucuronidase in leukocytes
      was markedly increased. After 1 month of therapy, enzyme levels dropped in all
      patients. In the patients who regularly followed the therapy, the enzyme levels
      remained stable for the next 20 months. In one patient who interrupted therapy
      for 2 months, the enzyme levels rose again. CONCLUSIONS: Lysosomal enzymes can be
      useful for monitoring biochemical changes in patients with Fabry disease
      receiving ERT. Though these findings refer to only a small number of patients,
      the correlation between beta-d-glucuronidase levels and ERT is interesting and
      might serve as a basis for further studies to define the potential of this enzyme
      in monitoring the effects of ERT in lysosomal storage disorders.

PMID- 15967646
TI  - Increased cerebral serotonin-2A receptor binding in depressed patients with
      myocardial infarction.
AB  - Serotonin (5-HT) has been implicated in the pathophysiology of depression. It is
      not known whether depression in post-myocardial infarction (MI) patients is also
      serotonin-mediated. In somatically healthy depressed persons, increased brain 5
      HT(2A) receptor binding has been reported in some studies. In animal studies,
      decreased serotonin activity was found after induction of MI. In the present
      study, it was hypothesized that depressed post-MI patients would exhibit
      increased brain 5-HT(2A) receptor binding compared with non-depressed post-MI
      patients. Single photon emission computed tomography (SPECT) with the radioligand
      123I-5-I-R91150, a 5-HT(2A) receptor antagonist, was used to study 5-HT(2A)
      receptor binding. SPECT scans were performed in nine depressed post-MI patients,
      10 non-depressed post-MI patients and 10 healthy control subjects. Results were
      analysed using statistical parametric mapping. Depressed post-MI patients showed
      increased 5-HT(2A) receptor binding compared with non-depressed post-MI patients,
      and MI patients showed decreased 5-HT(2A) receptor binding compared with control
      persons. Both post-MI depression and MI seem to be associated with changes in 5
      HT(2A) receptor binding.

PMID- 15967647
TI  - Volumetric analysis of sulci/gyri-defined in vivo frontal lobe regions in
      schizophrenia: Precentral gyrus, cingulate gyrus, and prefrontal region.
AB  - Methodological limitations in most previous magnetic resonance imaging (MRI)
      based volumetric studies might have contributed to the inconsistent results
      regarding the frontal lobe regions of schizophrenia. Thus, applying the largest
      sample to date among those that have fully taken account of the intrinsic
      anatomical landmarks, this study aimed at clarifying the volumetric alterations
      of the frontal lobe and its subregions in schizophrenia. Participants comprised
      59 patients with schizophrenia and 58 healthy controls. Measurements were
      performed on consecutive 1-mm-thick coronal slices reformatted from three
      dimensional 1.5-T MR images. The whole frontal lobe was demarcated and then
      subdivided into the precentral gyrus (PCG), anterior cingulate, and posterior
      cingulate, and the remainder temporarily as the prefrontal region. Patients with
      schizophrenia had significant cortical volume reductions in the bilateral whole
      frontal lobe, prefrontal region, PCG, posterior cingulate, and right anterior
      cingulate. This study has confirmed that patients with schizophrenia do have
      cortical volume reductions in the whole frontal lobe and its subregions. Volume
      reduction in the PCG suggests that the primary motor cortex might contribute to
      the mechanisms of schizophrenia, considering its important role in the processing
      of multiple motor-related cognitive functioning suggested by the recent
      literature.

PMID- 15967648
TI  - Smaller head of the hippocampus in Gulf War-related posttraumatic stress
      disorder.
AB  - Reductions in hippocampal volume and impairment in short-term verbal memory have
      been reported in Vietnam combat veterans with posttraumatic stress disorder
      (PTSD) and in women with abuse-related PTSD. The present investigation evaluated
      hippocampal volume and memory in Gulf War veterans. This research is timely given
      the ongoing war in Iraq and the anticipated high rates of PTSD among returning
      combat soldiers. Fourteen veterans with PTSD related to traumatic experiences
      during the Gulf War (1990-1991), 23 deployed veterans without PTSD, 22 non
      deployed reservists and 29 healthy civilians were studied. Volumes of the
      hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans,
      and hippocampal mediated memory function was evaluated. The head of the
      hippocampus was the only subregion that was significantly smaller in Gulf War
      veterans with PTSD than in healthy civilians. Deployed veterans with PTSD,
      deployed veterans without PTSD, and non-deployed reservists had significantly
      smaller whole hippocampal volume and lower scores on immediate and delayed verbal
      and visual retrieval compared with healthy civilians.

PMID- 15967649
TI  - Late interaction of syntactic and prosodic processes in sentence comprehension as
      revealed by ERPs.
AB  - The present study was designed to examine the processing of prosodic and
      syntactic information in spoken language. The aim was to investigate the long
      discussed relationship between prosody and syntax in online speech comprehension
      to reveal direct evidence about whether the two information types are interactive
      or independent from each other. The method of event-related potentials allowed us
      to sheet light on the precise time course of this relationship. Our experimental
      manipulation involved two prosodically different positions in German sentences,
      i.e., the critical noun in penultimate vs. final position. In syntactically
      correct sentences, a prosodic manipulation of the penultimate word gave rise to a
      late centroparietal negativity that resembled the classical N400 component. We
      interpreted the negativity as a correlate of lexical integration costs for the
      prosodically unexpected sentence-final word. Comparisons with syntactically
      incorrect sentences revealed that this effect was dependent on the sentences'
      grammatical correctness. When the prosodic manipulation was realized at the final
      word, we observed a right anterior negativity followed by a late positivity
      (P600). The right anterior negativity was present independent of the sentences'
      grammatical correctness. However, the P600 was not, as a late positivity was
      present for straightforward prosodic and syntactic violations but increased for
      the combined violations. This suggests that the right anterior negativity, and
      not the P600, should be considered as a pure prosodic effect. The combined data
      moreover suggest an interaction between prosody and syntax in a later time window
      during sentence comprehension.

PMID- 15967650
TI  - Preliminary study on phytoalexin induction in cucumber.
AB  - Inducer can induce new active composition and increase the content of the active
      composition in the plant. In this paper, we investigated the synthesis and
      accumulation of phytoalexin in cucumber seedlings which were induced by chemical
      inducer of the salicylic acid (SA) and physical inducer. Analyzed by experiment
      of antifungal activity, thin-layer chromatography (TLC) and high-performance
      liquid chromatography (HPLC), the result was that both SA and stress can induce
      the synthesis and accumulation of phytoalexin in cucumber seedlings. But the
      content of phytoalexin induced by SA was lower than it induced by stress. And in
      this paper, another conclusion was that the transduction of physical signal and
      the chemical signal in the plant depended on the adhesion between cell wall and
      plasma and active oxidative species producted by stimulation.

PMID- 15967651
TI  - A comparative study of the utility of two superdisintegrants in microcrystalline
      cellulose pellets prepared by extrusion-spheronization.
AB  - This study evaluated the utility of including superdisintegrants (croscarmellose
      sodium or sodium starch glycolate) in microcrystalline cellulose extrusion
      spheronization pellets as a means of increasing the dissolution rate of poorly
      water-soluble drugs. The model drug was hydrochlorothiazide, with water or
      water/ethanol as wetting agent for pellet preparation. Neither disintegrant had
      significant effects on pellet morphology, flow properties or mechanical
      resistance. Neither disintegrant caused disintegration of the pellet in drug
      dissolution medium. Nevertheless, the disintegrants afforded a modest increase in
      drug dissolution rate, attributable to the observed increase in pellet micropore
      volume. Drug dissolution rate was slightly higher in pellets prepared with sodium
      starch glycolate, probably because of this disintegrant's higher swelling
      capacity.

PMID- 15967652
TI  - Development of an enteric-coated, layered multi-particulate formulation for ileal
      delivery of viable recombinant Lactococcus lactis.
AB  - Layering of recombinant hIL-10 producing Lactococcus lactis (L. lactis Thy12) on
      inert carriers is a promising technique for the preparation of a multi
      particulate formulation of viable, hIL-10 producing L. lactis. To improve
      viability after layering and storage, L. lactis Thy12 was layered in different
      matrices (10% skim milk and/or 2.5, 5, 10% inulin). After layering, the highest
      viability was obtained in the 10% skim milk supplemented with 5% inulin matrix
      (8.7%). However, upon storage, 10% skim milk alone yielded the highest viability.
      Thereby, layered L. lactis Thy12 showed superior long term stability in
      comparison with freeze-dried L. lactis Thy12. The layering process was performed
      during 3h without encountering technical problems, with good layer consistence
      and constant viability. Enteric properties were obtained with a 30% Eudragit L30D
      55 or 15% Eudragit FS30D coating and maintained during an initial six months
      storage period (-20 degrees C/20% RH). After in vitro simulation of the gastric
      stage, only 5% of the bacteria remained viable in Eudragit L30D-55 coated
      pellets, contrary to 85% in Eudragit FS30D coated pellets, indicating its
      superior protective capacity against gastric fluid. After eight months storage (
      20 degrees C), 80% of the initial L. lactis Thy12 remained viable in the Eudragit
      FS30D coated pellets.

PMID- 15967653
TI  - Baclofen-loaded microspheres in gel suspensions for intrathecal drug delivery: in
      vitro and in vivo evaluation.
AB  - Severe spasticity is a very disabling disorder treated by continuous baclofen
      intrathecal infusion which unfortunately remains an expensive and uncomfortable
      treatment. In order to address these issues, new sustained release formulations
      designed for intrathecal baclofen delivery were sought with the aim of minimising
      the burst effect of baclofen which can lead to toxicity. Baclofen was
      encapsulated in poly(lactide-co-glycolide) (PLGA) microspheres which were then
      dispersed in chitosan thermosensitive gels, Pluronic PF-127 gels,
      carboxymethylcellulose solutions or Ringer lactate solution. The release rate was
      assessed in vitro using continuous flow cells and in vivo after intrathecal
      injection in goats: baclofen was quantified in cerebrospinal fluid (CSF) and
      plasma, and the associated pharmacological effect was evaluated. The results
      showed that the burst effect was reduced by at least a factor of 2 in vitro,
      after microsphere dispersion in viscous media. In vivo, PF-127 gel was found to
      be the best vehicle to reduce the burst effect by a factor of 10 in CSF, and by a
      factor of 2 in plasma. The toxic effect of baclofen due to the burst effect was
      reduced by the dispersion in PF127 gels. Therapeutic levels of baclofen in CSF
      were maintained during at least 1 month.

PMID- 15967654
TI  - MHC multimer technology: current status and future prospects.
AB  - The detection of antigen-specific T cell responses by MHC multimer staining is
      rapidly becoming one of the core immunological techniques, and the technology to
      produce MHC multimers has been optimized substantially in recent years.
      Furthermore, recent work demonstrates the potential of high-throughput detection
      of T cell responses and suggests that manipulation of T cell responses through
      the use of multimeric MHC reagents is also feasible.

PMID- 15967656
TI  - Adding value to fusion proteins through covalent labelling.
AB  - Recombinant proteins are often expressed with an additional polypeptide the role
      of which is to aid purification, detection or functional studies. Recently, the
      role of these tags has been extended to mediate the labelling of the protein of
      interest with chemically diverse compounds. These approaches are of importance
      for protein science as they allow proteins to be equipped with properties that
      cannot be genetically encoded and also enable the use of a single fusion protein
      for several different applications. Several new approaches have been developed
      for the covalent labelling of fusion proteins both in living cells and in vitro.

PMID- 15967657
TI  - Axes formation and RNA localization.
AB  - Axes formation in flies and frogs largely depends on RNA localization pathways
      functioning in the oocytes. It is thought that motors moving along the
      cytoskeleton enable the selective transport of RNAs to different destinations
      during oocyte development. Many of the steps in RNA localization are conserved,
      despite the existence of a variety of mechanisms, including the formation of
      nuclear ribonucleoprotein complexes, and active transport along microtubules.

PMID- 15967658
TI  - Signals that regulate stem cell activity during plant development.
AB  - Plant stem cells are used continuously to generate new structures during the
      entire life-span of the organism. In the adult plant, stem cells are found in
      specialized structures called meristems. The meristems contain the stem cell
      niche together with rapidly dividing daughter cells that will ultimately
      differentiate into specific cell types. Some of the master genes that orchestrate
      the establishment and maintenance of the stem cell niche have now been identified
      in both the root and the shoot. Recent results show that these genes also
      determine the fate of the stem cells and that feedback signals from
      differentiated cells are involved in stem cell specification. These advances have
      provided a framework to understand how short-range and long-range signals are
      integrated to specify and position the stem cell niche in the meristems, and how
      the differentiation potential of plant stem cells is controlled.

PMID- 15967659
TI  - Model systems: mechanisms involved in the loss of sensitivity to letrozole.
AB  - A number of models have been used to study the development and treatment of
      breast cancer. Since most breast cancer patients are postmenopausal and treated
      with hormone therapy, we developed a model to simulate this type of patient.
      Tumors of human estrogen receptor (ER)-positive breast cancer cells transfected
      with aromatase (MCF-7Ca) are grown in immune suppressed mice. In this model, we
      have explored a number of strategies to optimize the antitumor efficacy of
      treatment such as combining the non-steroidal aromatase inhibitor letrozole with
      the antiestrogens, tamoxifen. This combination resulted in tumor suppression
      similar to the antiestrogen alone, but was less effective than letrozole alone.
      Clinical findings with the non-steroidal inhibitor anastrozole in combination
      with tamoxifen (ATAC trial) were consistent with our results. Although letrozole
      was the most effective single agent tested in the model, tumors ultimately began
      to grow during continued treatment. To investigate the mechanisms by which tumors
      adapt to growth during letrozole treatment, we determined the expression of
      signaling proteins in tumors during the course of letrozole treatment compared to
      the tumors of control mice. We found that tumors initially up regulated the ER,
      but subsequently receptor levels decreased in tumors unresponsive to letrozole.
      Adapter proteins (p-Shc and Grb-2) as well as all of the signaling proteins in
      the MAPK cascade (p-Raf, p-Mek1/2, and p-MAPK), but not Akt, were increased in
      tumors no longer responsive to letrozole. The results suggest that tumor cells
      adapt to estrogen deprivation during letrozole treatment by activation of
      alternate signaling pathways to increase transcription. When letrozole was
      combined with the pure antiestrogen fulvestrant, to down regulate ER, the
      combination was more effective than either letrozole or fulvestrant alone. Tumors
      regressed by 45% and were maintained without growth for the duration of the
      experiment (29 weeks). Down regulation of ER by fulvestrant may prevent cross
      talk between these signaling pathways. The results suggest that achieving more
      complete estrogen blockade may delay development of hormone-independent signaling
      pathways regulating proliferation.

PMID- 15967660
TI  - Effect of microwave irradiated Methanosarcina barkeri DSM-804 on biomethanation.
AB  - Methanosarcina barkeri DSM-804, a methanogenic bacterium, when exposed to
      microwave radiation of frequencies ranging from 13.5 to 36.5 GHz, showed faster
      growth in comparison to the unirradiated bacterial culture. Methane concentration
      in the biogas generated from the irradiated culture was higher than that from
      unirradiated one, which was to 76.3% on the 15th day of incubation at a microwave
      radiation frequency of 31.5 GHz, 10 dbm power when irradiated for 2 h.
      Microscopic study of pure culture revealed that the cells of M. barkeri were more
      in number and their cell diameter was enlarged by 20%. Inoculation of the culture
      in a biogas digester containing a combination of jute waste and vegetable market
      waste as substrate increased the efficacy of biomethanation and reduced its lag
      phase significantly.

PMID- 15967661
TI  - Productivity of laccase in solid substrate fermentation of selected agro-residues
      by Pycnoporus sanguineus.
AB  - A comparative study on solid substrate fermentation (SSF) of sago 'hampas', oil
      palm frond parenchyma tissue (OPFPt) and rubberwood sawdust with Pycnoporus
      sanguineus for laccase production was carried out. Optimal mycelial growth of
      Pyc. sanguineus was observed on all the substrates studied over a 21 days time
      course fermentation. Laccase productivity was highest during degradation of sago
      'hampas' and OPFPt and a range from 7.5 to 7.6 U/g substrate on the 11th day of
      fermentation compared to degradation of rubberwood sawdust with a maximum laccase
      productivity of 5.7 U/g substrate on day 11 of SSF. Further optimization of
      laccase production was done by varying the inoculum age, density and nitrogen
      supplementation. SSF of OPFPt by Pyc. sanguineus gave maximum productivity of
      laccase of 46.5 U/g substrate on day 6 of fermentation with a 30% (w/w) of 4
      weeks old inoculum and 0.92% nitrogen in the form of urea supplemented in the
      substrate. The extraction of laccase was also optimized in this study. Recovery
      of laccase was fourfold higher at 30.6 U/g substrate on day 10 of SSF using
      unadjusted tap water at pH 8.0 as extraction medium at 25+/-2 degrees C compared
      to laccase recovery of 7.46 U/g substrate using sodium acetate buffer at pH 4.8
      at 4 degrees C. Further optimization showed that laccase recovery was increased
      by 50% with a value of 46.5 U/g substrate on day 10 of SSF when the extraction
      medium was tap water adjusted to pH 5.0 at 25+/-2 degrees C.

PMID- 15967662
TI  - Concise synthesis and voltammetric studies of dielsiquinone, a cytotoxic
      azaanthraquinone.
AB  - We have developed a concise synthesis of dielsiquinone 1, a potent cytotoxic
      agent related to anthraquinones. Electrochemical studies have shown that
      dielsiquinone is reduced to a semiquinone radical that does not react with O2 to
      generate toxic reactive oxygen species. These results strongly suggest that 1
      should be less cardiotoxic than anthracyclines used in clinic and may therefore
      provide the basis for the development of safer anticancer drugs.

PMID- 15967663
TI  - Design, synthesis and evaluation of racemic 1-(4-hydroxyphenyl)-2-[3-(substituted
      phenoxy)-2-hydroxy-1-propyl]amino-1-propanol hydrochlorides as novel uterine
      relaxants.
AB  - Novel 1-(4-hydroxyphenyl)-2-[3-(substituted phenoxy)-2-hydroxy-1-propyl]amino-1
      propanol hydrochlorides were designed based on the pharmacophore for potent
      uterine relaxant activity and by utilizing the principles of structural
      hybridization. The designed molecules were synthesized as racemates by a novel
      route and were evaluated for uterine relaxant activity in vitro on isolated rat
      uterus and in vivo in pregnant rats. Their cAMP-releasing potential was studied
      using rat uterus tissue homogenates by the cAMP [(3)H] assay, and cardiac
      stimulant potential was evaluated on isolated guinea pig right atrium. All
      compounds exhibited potent uterine relaxant activity in vitro and produced a
      significant delay in the onset of labour in pregnant rats; their cAMP-releasing
      potential was slightly less, while their cardiac stimulant potential was
      insignificant as compared to isoxsuprine hydrochloride.

PMID- 15967664
TI  - Synthesis and biological evaluation of novel angularly fused polycyclic
      coumarins.
AB  - In a three-step sequence, an array of angularly fused polycyclic heterocycles
      with coumarin, benzofuran and pyridine rings were synthesized from 4
      bromomethylcoumarins and salicylonitrile. All the final compounds were fully
      characterized and screened for anti-microbial, anti-inflammatory and analgesic
      activities. Several compounds exhibited promising inflammation inhibiting and
      anti-microbial properties.

PMID- 15967665
TI  - Using worms to better understand how Bacillus thuringiensis kills insects.
AB  - Bacillus thuringiensis is widely used as a biological pesticide to control
      insects that either cause damage to crops or transmit disease. That it can also
      target the model organism Caenorhabditis elegans has not only provided exciting
      new insights into how the toxins produced by the bacterium target their victims
      but also how target insects counter the attack. Modern approaches such as reverse
      genetics and microarray technology have revealed novel receptors for the toxins
      and possible signal transduction pathways induced within the host following
      intoxication. This article will discuss how these findings fit in with current
      models and how they might influence future studies.

PMID- 15967666
TI  - Changes of meniscal interhorn distances: an in vivo magnetic resonance imaging
      study.
AB  - The aim of this study was to evaluate the changes of the internal (IID) and
      external meniscal interhorn distance (EID) of the medial and the lateral meniscus
      under loading. Sagittal magnetic resonance images of 15 knees were studied. The
      medial and lateral meniscus were examined with the knee at 0 degrees and 30
      degrees of flexion, under no load, with load equal to 50% of body weight and with
      load equal to 100% of body weight. Under no load, the mean IID was 19.9 mm for
      the medial meniscus and 12.3 mm for the lateral meniscus and the mean EID was
      44.6 mm for the medial meniscus and 34.4 mm for the lateral meniscus. Under load
      equal to 50% and 100% of patient's body weight, there was a significant increase
      in both distances (p<0.05). Under constant loading, flexion of the knee from 0
      degrees to 30 degrees , decreased the EID of both menisci. In conclusion, loading
      increases both IID and EID. Knee position affects only the EID. The quality of
      magnetic resonance images may affect the reliability of such measurements.

PMID- 15967667
TI  - Evaluation of patello-femoral alignment using MRI.
AB  - In evaluating patello-femoral alignment, it is not enough to assess the
      conformity of the joint two-dimensionally, the direction of the extensor
      mechanism must be examined three-dimensionally. Using magnetic resonance imaging
      (MRI), we adopted an ideal extensor mechanism plane intersecting the patellar
      facet of the femur centrally and perpendicularly. We evaluated the alignment
      according to the extent to which the patella and/or the tibial tuberosity
      deviated from the plane. The results suggested that our method is useful for
      indicating proximal and distal realignment. Furthermore, two-dimensional finite
      element analysis in the patello-femoral joint showed that peak stress was
      significantly higher in the dislocation group than in the no-dislocation group.
      This indicates that osteoarthritic change in the future is a risk in the
      dislocation group.

PMID- 15967668
TI  - Achieving ligament stability and correct rotational alignment of the femur in
      knee arthroplasty: a study using the Medial Pivot knee.
AB  - In a series of 90 Medial Pivot arthroplasties rotational alignment of the femur
      was achieved by provisionally reconstructing the lateral side of the joint and
      tensioning the medial side with feeler gauges. Axial CT scans were employed to
      measure the rotational alignment relative to surgical epicondylar axis. In valgus
      knees the cutting block was externally rotated to adjust for posterolateral bone
      loss. The mean rotational alignment of the femur was 0.6 degrees of external
      rotation (S.D. 1.3, range 3 degrees of ER to 4 degrees of IR). The mean laxity of
      the medial ligament was 1 mm in flexion (SD 1, range 0-5 mm) and 0.5 mm in
      flexion (S.D. 0.5, range 0-2 mm) In those knees in which the medial ligament had
      been released the CT alignment was perfect, but when internally rotated against
      the hip 3-4 mm of gapping was noted. In valgus knees the mean rotation of the
      femoral component was 0.8 degrees of internal rotation (S.D. 1.5, range 1 degrees
      of IR to 4 degrees of ER). In spite of externally rotating the cutting block
      there was still a tendency to internally rotate the femur in some knees. This
      simple technique achieves the two goals of ligament stability and correct
      rotational alignment in a high proportion of cases. It may be applicable to any
      instrument system which employs posterior referencing.

PMID- 15967669
TI  - Depletion of rabphilin 3A in a transgenic mouse model (R6/1) of Huntington's
      disease, a possible culprit in synaptic dysfunction.
AB  - Huntington's disease (HD) is a hereditary neurodegenerative disorder
      characterized by progressive psychiatric, cognitive, and motor disturbances. We
      studied the expression of synaptic vesicle proteins in the R6/1 transgenic mouse
      model of HD. We observed that the levels of rabphilin 3A, a protein involved in
      exocytosis, is substantially decreased in synapses of most brain regions in R6/1
      mice. The appearance of the reduction coincides with the onset of motor deficits
      and behavioral disturbances. Double immunohistochemistry did not show
      colocalization between rabphilin 3A and huntingtin aggregates in the HD mice.
      Using in situ hybridization, we demonstrated that rabphilin 3A mRNA expression
      was substantially reduced in the R6/1 mouse cortex compared to wild-type mice.
      Our results indicate that a decrease in mRNA levels underlie the depletion of
      protein levels of rabphilin 3A, and we suggest that this reduction may be
      involved in causing impaired synaptic transmission in R6/1 mice.

PMID- 15967670
TI  - Prenatal stress elicits regionally selective changes in basal FGF-2 gene
      expression in adulthood and alters the adult response to acute or chronic stress.
AB  - Exposure to stress during pregnancy influences the trajectory of brain
      development resulting in permanent alterations that may contribute to increased
      susceptibility to subsequent cognitive or neuropsychiatric disorders. In this
      manuscript, we examined the effects of prenatal stress on the expression of basic
      fibroblast growth factor (FGF-2), an important molecular regulator of development
      and plasticity, in adult male rats under basal conditions as well as in response
      to acute or chronic stress. Baseline FGF-2 mRNA levels were differentially
      influenced by gestational stress in a variety of brain regions, with significant
      decreases in prefrontal cortex and increases in entorhinal cortex and striatum.
      By itself, postnatal stress similarly decreased trophic factor expression in
      prefrontal cortex while evoking stimulation elsewhere. Gestational stress altered
      the pattern of FGF-2 expression in response to adult stress, completely reversing
      the pattern in the prefrontal cortex (stimulatory instead of inhibitory),
      blunting the response in the entorhinal cortex and desensitizing the response in
      the striatum. These effects point to a unique interference of chronic prenatal
      stress with both ongoing FGF-2 expression and its responses to subsequent
      stressors, lasting into adulthood. Given the multifaceted role of FGF-2 in
      synaptic development, maintenance and plasticity, these data provide detailed
      mechanistic evidence as to how prenatal stress elicits lifelong effects on
      synaptic function. The abnormal modulation of FGF-2 gene expression in specific
      brain regions in response to subsequent stress in adulthood may impair the normal
      adaptive responses of the cell to challenging situations.

PMID- 15967671
TI  - Development and composition of the seeds of nine genotypes of the Medicago
      truncatula species complex.
AB  - The seed development and composition of Medicago truncatula Gaertn., the new
      model plant for grain legumes, was studied using nine genotypes of the species
      complex: M. truncatula-Medicago littoralis (M. truncatula). The seed development
      of M. truncatula was very similar to that of other legumes, the only notable
      exception being the presence, in the mature seed, of an endosperm layer that is
      absent in grain legumes. During early embryogenesis and until mid-maturation,
      transient storage of starch occurred in the seed coat and embryo. This temporary
      storage probably contributed to the early development of the embryo and reserve
      synthesis. During maturation the synthesis and accumulation of proteins and oil
      took place at quasi-constant rates. Conversely oligosaccharides, mainly
      stachyose, were synthesised only during late maturation and at the beginning of
      desiccation. Proteins represented the major class of storage compounds and their
      average amino acid composition was found to be very close to that of pea and
      robust in various environmental conditions. Similar compositions between the two
      species and other grain legumes were also found for the fatty acids and the
      soluble sugars; most of these characters varied depending on the various
      environmental conditions used for seed production. All these similarities fully
      justify the use of M. truncatula as a model plant for genomic approaches to grain
      legume improvement. The major difference between M. truncatula seeds and European
      grain legume seeds resides in the nature of their carbon storage namely
      triacylglycerides for M. truncatula and starch for pea and faba bean.

PMID- 15967672
TI  - Surgery for right ventricle to pulmonary artery conduit obstruction: risk factors
      for further reoperation.
AB  - OBJECTIVE: To identify the surgical approaches and risk factors which influence
      longevity of right ventricle to pulmonary artery (RV-PA) conduits following first
      reoperation for obstruction. METHODS: Between January 1993 and August 2003, 114
      patients underwent 141 reoperations for RV-PA conduit obstruction. Diagnoses
      included 'Truncus Arteriosus' (n=52), 'Pulmonary atresia/Tetralogy of fallot'
      (n=39), 'Double outlet right ventricle' (n=10), 'Transposition of great arteries,
      VSD, and pulmonary atresia' (n=9), and the 'Ross operation' (n=4). All patients
      had undergone a previous biventricular repair. The first reoperation for conduit
      obstruction was performed in 112 hospital survivors by: total conduit replacement
      (Group A, n=73) with valved (homograft=10 and xenograft=54) or non-valved (n=9)
      conduit, and patch enlargement of the obstructed RV outflow tract with
      preservation of the posterior and sides of the conduit wall after removing of the
      fibrocalcific peel and degenerated valve (Group B, n=39). Mean age at first
      reoperation was 8.8+/-6.7 and 7.5+/-5.3 years in patients of groups A and B,
      respectively. Seven patients in Group A and 18 in Group B required a second
      reoperation and two patients in Group B a third reoperation. RESULTS: There were
      two hospital deaths and no late deaths. Mean follow-up was 5.8+/-3.2 years. Risk
      factors for second reoperation by univariate analysis were: homograft conduit use
      (P=0.004), Group B surgical approach (P=0.0001), higher RV-PA systolic pressure
      gradient at discharge (P=0.02), and age <5-years-old (P=0.01). Multivariate
      analysis showed that inclusion in Group B and younger age (<5-years-old) at
      repair were independent risk factors for second reoperation. Group B surgical
      approaches had higher RV-PA systolic pressure gradient at discharge (P=0.02) and
      required more PA bifurcation repair at the time of second reoperation (P=0.05).
      Freedom from second reoperation for conduit obstruction was significantly higher
      in Group A patients at 5 and 8 years (P<0.04) and those with xenografts rather
      than homograft (P=0.04). CONCLUSIONS: Our results support the optimal surgical
      approach for RV-PA conduit obstruction is total replacement with a xenograft. RV
      outflow reconstruction by other techniques without complete dissection of PA
      bifurcation does not completely relieve the stenosis and could cause early
      restenosis. Higher systolic gradients at discharge and younger age at first
      reoperation are predictors of earlier reoperation.

PMID- 15967673
TI  - Spatial and temporal variations of the inherent and apparent optical properties
      in a shallow coastal lake.
AB  - Apparent and inherent optical properties in the coastal lagoon of Fogliano were
      measured in three seasonal surveys in 2002. Irradiance data from in situ
      measurements of ultraviolet and visible wavebands permitted to estimate the
      related attenuation coefficients. Laboratory extinction measurements on filtered
      (0.22 microm) and unfiltered water samples were also performed. The integrated
      approach between in situ and laboratory measurements allowed the determination of
      the role of the suspended and dissolved matter in the attenuation and extinction
      of ultraviolet and visible radiation within the water column. As noted, the
      impact of the suspended and dissolved matter on the lake optical quality was
      influenced by wind resuspension of particulate matter: the relative role of
      dissolved matter in the absorption of UV and visible radiation was prevailing at
      low wind velocity conditions (less than 2.2 m s(-1)), while at high wind
      velocities (3.9 m s(-1)), particulate matter resuspension strongly influenced the
      attenuation and the extinction measurements. The extinction in the analyzed
      wavelengths of filtered and unfiltered water samples and the in situ irradiance
      measurements allowed us to define new optical parameters and important
      correlations with limnological and classical optical measurements. By sampling at
      high spatial resolution (18 stations in 4 km2), it was possible to evidence a
      spatial gradient of the optical and limnological properties, these distributions
      showed a consistent pattern in all three surveys, and were important for the
      characterization of the chromophoric dissolved organic matter that was estimated
      with the spectral slope of the extinction curve spectra. A relatively higher
      spectral slope was found in the southern basin with respect to the northern,
      where the maximum values of the attenuation coefficients and limnological
      parameters were found. These results suggest different sources of dissolved
      organic matter and/or a different level of photobleaching.

PMID- 15967674
TI  - Heat-induced and light-induced isomerization of the xanthophyll pigment
      zeaxanthin.
AB  - Zeaxanthin is a xanthophyll pigment that plays important physiological functions
      both in the plant and in the animal kingdom. All-trans is a stereochemical
      conformation of zeaxanthin reported as specific for the thylakoid membranes of
      the photosynthetic apparatus and the retina of an eye. On the other hand, the
      pigment is subjected, in natural environment, to the conditions that promote
      stereochemical isomerization, such as illumination and elevated temperature. In
      the present work, the light-induced and heat-induced (the temperature range 35-95
      degrees C) isomerization of all-trans zeaxanthin in organic solvent environment
      has been analyzed by means of the HPLC technique. The 13-cis conformation has
      been identified as a major one among the isomerization products. The activation
      energy of the all-trans to 13-cis isomerization has been determined as 83 +/- 4
      kJ/mol and the activation energy of the back reaction as 30 +/- 7 kJ/mol. The
      reaction of isomerization of the all-trans zeaxanthin at 25 degrees C was
      substantially more efficient upon illumination. Four different wavelengths of
      light have been selected for photo-isomerization experiments: 450, 540, 580 and
      670 nm, corresponding to the electronic transitions of zeaxanthin from the ground
      state to the singlet excited states: 1(1)Bu+,3(1)Ag-,1(1)Bu- and 2(1)Ag-,
      respectively. The quantum efficiency of the all-trans zeaxanthin isomerization
      induced by light at different wavelengths: 450, 540, 580 and 670 nm was found to
      differ considerably and was in the ratio as 1:15:160:29. The sequence of the
      quantum efficiency values suggests that the carotenoid triplet state 1(3)Bu,
      populated via the internal conversion from the 1(3)Ag triplet state which is
      generated by the intersystem crossing from the 1(1)Bu- state may be involved in
      the light-induced isomerization. A physiological importance of the isomerization
      of zeaxanthin in the retina of an eye, photosynthetic apparatus and of the
      pigment active as a blue light photoreceptor in stomata is briefly discussed.

PMID- 15967675
TI  - Low power laser radiation at 685 nm stimulates stem-cell proliferation rate in
      Dugesia tigrina during regeneration.
AB  - Today's scientific interest in tissue engineering for organ transplantations and
      regeneration from stem cells, allied with recent observations on biostimulation
      of tissues and cells by laser radiation, stands as a strong motivation for the
      present work, in which we examine the effects of the low power laser radiation
      onto planarians under regenerative process. To investigate those effects, a
      number of 60 amputated worms were divided in three study groups: a control group
      and two other groups submitted to daily 1 and 3 min long laser treatment sections
      at approximately 910 W/m2 power density. A 685 nm diode laser with 35 mW optical
      power was used. Samples were sent to histological analysis at the 4th, the 7th
      and the 15th days after amputation. A remarkable increase in stem cells counts
      for the fourth day of regeneration was observed when the regenerating worms was
      stimulated by the laser radiation. Our findings encourage further research works
      on the influence of optical radiation onto stem cells and tissue regeneration.

PMID- 15967676
TI  - Sensitivity to ALA-PDT of cell lines with different nitric oxide production and
      resistance to NO cytotoxicity.
AB  - In this work, we studied the in vitro interactions between aminolevulinic acid
      (ALA)-mediated photodynamic therapy (PDT) and nitric oxide (NO), as well as the
      interactions between ALA, porphyrins and some NO donors and precursors. We
      employed three murine adenocarcinoma cell lines: LM2, which does not produce NO;
      LM3, which produces NO, and LM3-SNP, a variant of LM3 resistant to NO producing
      the same amount of NO as the parental. We did not find cross-resistance between
      NO-induced cytotoxicity and ALA-PDT. In spite of the lower porphyrin synthesis,
      LM2 cells show the highest sensitivity to ALA-PDT. However, we hypothesised that
      this is not related to the lack of endogenous NO production, because modulation
      of NO levels did not modify the response to PDT in any of the cell lines. Two
      unexpected results were found: the enhancement of NO production from the donor
      sodium nitroprusside (SNP) induced by ALA in both cells and medium, and the
      inhibition by ALA of NO production from arginine. We also found that SNP strongly
      protected the cells from ALA-PDT by impairing porphyrin biosynthesis as a
      consequence of an inhibition of the enzyme ALA dehydratase. We were not able to
      evaluate the action of NO derived from SNP because of the unexpected porphyrin
      impairment. On the other hand, impairment of NO from Arginine driven by ALA,
      although not modulating in vitro the ALA-PDT response, by increasing in vivo
      blood flow, may be contributing to the mechanism of tumour cures.

PMID- 15967677
TI  - Reevaluating current models of thymic involution.
AB  - It is generally accepted that thymic involution commences, or at least
      accelerates, at puberty due to increases in sex steroid and declines in growth
      hormone production. As a result of these hormonal changes, the development of the
      most immature intrathymic progenitors is blocked. However, aspects of this model
      are now being questioned. The present chapter re-evaluates a number of findings
      on which traditional models of thymic involution are based and reviews new data
      that, taken together, indicate a need to revise current views of thymic
      involution.

PMID- 15967678
TI  - Deficient B lymphopoiesis in murine senescence: potential roles for dysregulation
      of E2A, Pax-5, and STAT5.
AB  - B lymphopoiesis in senescent mice is typically diminished and characterized by
      low pre-B cell numbers. The transcription factors E2A, Pax-5, and STAT5 have been
      implicated in the differentiation, proliferation, and survival of B cell
      precursors. In this review, we discuss the impairment of B lymphopoiesis during
      old age in the context of mechanisms at the molecular level responsible for the
      handling and turnover of these key transcriptional proteins. Alterations in the
      expression of E2A, Pax-5, and STAT5 may affect multiple stages of B cell
      development, contribute to reduced B lymphopoiesis, and preface changes in the
      "read-out" of the BCR repertoire during murine senescence.

PMID- 15967679
TI  - Dendritic cell subsets and immune regulation in the lung.
AB  - The lung is continuously exposed to inhaled particles, microbes and harmless
      antigens to which either immunity or tolerance is induced. Dendritic cells are
      mainly recognized for their extraordinary capacity to induce a primary immune
      response in the lung. Recent evidence suggests that particular subsets of DCs are
      essential in the decision between immunity or tolerance. Moreover, DCs play an
      essential role during secondary immune responses in the lung, where they control
      the inflammatory reaction. These novel concepts are of particular interest in
      understanding the pathogenesis of asthma, a disorder of aberrant immune
      reactivity to inhaled harmless allergens.

PMID- 15967680
TI  - Genomic organisation and expression of the natural killer cell enhancing factor
      (NKEF) gene in channel catfish, Ictalurus punctatus (Rafinesque).
AB  - The gene encoding Natural Killer Cell Enhancing Factor (NKEF) was identified in
      clones from a gynogenetic channel catfish BAC library. NKEF gene sequence (5.2
      kb) was obtained by direct sequencing of BAC clones. The catfish NKEF gene
      contains one non-coding exon, five coding exons and five introns. A putative TATA
      box and other transcription factor binding sites were identified in the promoter
      region. The NKEF amino acid sequence is highly conserved between fish and
      mammals. Gene expression, measured by real-time quantitative PCR, was detected in
      all major tissues with the highest level of expression in stomach and heart and
      lowest levels in gonad and pituitary gland. Catfish NKEF mRNA levels were
      slightly upregulated 8 and 24 h after injection of lipopolysaccharide. A TAA
      repeat microsatellite was identified in a BAC clone containing the NKEF gene, and
      this locus contained at least 12 alleles in a random-bred catfish population.
      Multipoint linkage analysis in two reference families placed the NKEF gene on
      linkage group U18, 5.1 cM from locus IpCG0177 (r=0.05; LOD=45.8), 6.0 cM from a
      novel immune type receptor, syntenic (40 cM) with T-cell receptor alpha, and not
      linked with MHC loci.

PMID- 15967681
TI  - Cloning of an orange-spotted grouper (Epinephelus coioides) Mx cDNA and
      characterisation of its expression in response to nodavirus.
AB  - Molecular cloning and nucleotide sequencing of cDNA encoding an orange-spotted
      grouper (Epinephelus coioides) homolog of Mx ("OsgMx") was conducted and its
      possible role in fish immunity was analysed. Similar to mammalian Mx, the OsgMx
      are members of a family of interferon-inducible genes that are expressed by cells
      in response to nodavirus and iridovirus naturally-infected. Expression of OsgMx
      mRNA was noticeably upregulated in all tissues by nodavirus naturally-infected
      grouper. The transcription of OsgMx gene increased 6 h after intramuscular
      injection of nodavirus experimentally-infected fish and peaked at 72 h in their
      brains. Analysis of the 5'-flanking sequence of the gene shows that as in
      pufferfish and zebrafish, the OsgMx promoter contains two potential interferon
      stimulated response element (ISRE) responsible for the induction of interferon
      inducer polyinosinic-polycytidylic acid (Poly[I:C]). Transient transfection of
      grouper cells in gfp-reporter gene assays shows that the activation of the
      grouper Mx promoter fragment by Poly[I:C] is sufficient to allow the expression
      of green fluorescent protein (GFP). These results may provide a possible
      regulated pathway against nodavirus.

PMID- 15967682
TI  - Molecular phylogeny of funnel-eared bats (Chiroptera: Natalidae), with notes on
      biogeography and conservation.
AB  - Two assumptions have framed previous systematic and biogeographic studies of the
      family Natalidae: that it comprises a few widespread species, and that extant
      lineages originated in Mexico and/or Central America. This study analyzes new
      sequence data from the mitochondrial cytochrome b and the nuclear Rag2, to
      clarify species boundaries and infer relationships among extant taxa. Fixed
      differences in cytochrome b coincide with published morphological characters, and
      show that the family includes at least eight species. One newly recognized
      species is known to live from a single locality in Jamaica, suggesting immediate
      conservation measures and underscoring the urgency of taxonomic revision. Among
      the three genera, Chilonatalus and Natalus form a clade, to the exclusion of
      Nyctiellus. This phylogeny and the geographic distribution of natalids, both
      extant and extinct, are hardly compatible with a Middle American origin for the
      group. Instead, extant natalids appear to have originated in the West Indies. The
      threat of Caribbean hurricanes early in their evolutionary history might account
      for the specialized cave roosting that characterizes all natalids, even
      continental species.

PMID- 15967683
TI  - Drugs effects on ventricular repolarization: a critical evaluation of the
      strengths and weaknesses of current methodologies and regulatory practices.
AB  - A growing number of drugs and drug combinations inhibit cardiac potassium ion
      conductance and ventricular repolarization, and increase cardiac APD, QT
      interval, and risk of potentially fatal TdP. The past decade has seen an
      explosion of research advances into the mechanism of action underpinning these
      observations, and an unprecedented level of collaboration between academia,
      industry, and regulatory authorities to define effective strategies for accurate
      prediction of increased TdP risk (if any) in humans, based upon nonclinical
      and/or clinical endpoints. Because the incidence of TdP is so very low, even for
      drugs for which the association is known, the risk can only be assessed based
      upon surrogate markers (signals) in in vitro and in vivo non-clinical studies as
      well as in clinical trials. In this article, we review both the strengths and
      weaknesses of current methodologies and regulatory practices for assessment of
      TdP risk for pharmaceuticals.

PMID- 15967684
TI  - Unusual ipsilateral hyperkinetic automatisms in SMA seizures.
AB  - PURPOSE: To describe repetitive movements of the right arm possibly originating
      from the ipsilateral SMA area in two drug-resistant epileptic patients. METHODS:
      Two epileptic patients (one female, one male, 35 and 36 years old, respectively)
      were submitted to pre-surgical evaluation including history, neurological
      examination, long-term video-EEG monitoring, interictal and ictal SPET, MRI and
      fMRI, neuropsychological assessment. Invasive recordings
      (stereoelectroencephalography) were also performed. RESULTS: In both patients
      ictal semiology was characterized by very stereotyped repetitive right arm
      movements, i.e. tapping towards the thorax (movement rate of 6-7 Hz and 3-4 Hz
      for the two subjects, respectively). Seizures in the first patient, whose
      epilepsy was cryptogenetic, originated from the right pre-SMA area, which was
      surgically removed. She is seizure free 2 years after the operation. In the
      second patient, in whom a right pre-frontal post-abscess porencephaly was
      disclosed, the epileptogenic zone included the lesion and surrounding areas,
      while the SMA area was involved less consistently. CONCLUSIONS: Even if,
      according to literature, SMA epilepsy is predominantly characterized by postural
      manifestations, ipsilateral repetitive movements could be a relevant sign in this
      kind of epilepsy, as showed in our first patient. The presence of similar
      semiology in the second patient, might suggest that the symptomatogenic zone
      involved SMA area.

PMID- 15967685
TI  - Regeneration of articular cartilage--evaluation of osteochondral defect repair in
      the rabbit using multiphasic implants.
AB  - OBJECTIVE: To investigate whether two different multiphasic implants could
      initiate and sustain repair of osteochondral defects in rabbits. The implants
      address the malleable properties of cartilage while also addressing the rigid
      characteristics of subchondral bone. DESIGN: The bone region of both devices
      consisted of D, D-L, L-polylactic acid invested with hyaluronan (HY). The
      cartilage region of the first device was a polyelectrolytic complex (PEC)
      hydrogel of HY and chitosan. In the second device the cartilage region consisted
      of type I collagen scaffold. Eighteen rabbits were implanted bilaterally with a
      device, or underwent defect creation with no implant. At 24 weeks, regenerated
      tissues were evaluated grossly, histologically and via immunostaining for type II
      collagen. RESULTS: PEC devices induced a significantly better repair than
      untreated shams. Collagen devices resulted in a quality of repair close to that
      of the PEC group, although its mean repair score (19.0+/-4.2) did not differ
      significantly from that of the PEC group (20.4+/-3.7) or the shams (16.5+/-6.3).
      The percentage of hyaline-appearing cartilage in the repair was highest with
      collagen implants, while the degree of bonding of repair to the host, structural
      integrity of the neocartilage, and reconstitution of the subchondral bone was
      greatest with PEC devices. Cartilage in both device-treated sites stained
      positive for type II collagen and GAG. CONCLUSIONS: Both implants are capable of
      maintaining hyaline-appearing tissue at 24 weeks. The physicochemical region
      between the cartilage and bone compartments makes these devices well suited for
      delivery of different growth factors or drugs in each compartment, or different
      doses of the same factor. It also renders these devices excellent vehicles for
      chondrocyte or stem cell transplantation.

PMID- 15967686
TI  - Successful nonoperative management of chronic osteoarthritis pain of the knee:
      safety and efficacy of retreatment with intra-articular hyaluronans.
AB  - CONTEXT: Although there are many nonsurgical therapies available for the
      treatment of pain associated with osteoarthritis (OA), their long-term use and
      safety have not been systematically followed. Intra-articular hyaluronan therapy
      has been used in the treatment of symptoms associated with OA of the knee with a
      very favorable safety profile. Five intra-articular hyaluronan products are
      approved in the US. No systematic review of the safety and efficacy of their
      chronic use has been reported. OBJECTIVE: To evaluate the literature on the
      efficacy and safety of repeat courses of hyaluronan therapy in patients with OA
      of the knee. DATA SOURCES: MEDLINE, EMBASE, searched through October 2004. STUDY
      SELECTION: Databases were searched using the terms hyaluronan, sodium
      hyaluronate, hyaluronic acid, hylan, hylan G-F 20, osteoarthritis, adverse
      events, repeat treatment, and multiple courses. DATA SYNTHESIS: There are some
      data that support the benefit and safety of repeat treatment for all products.
      Data also indicate that one formulation of sodium hyaluronate (molecular weight
      [MW] 500-730 kDa) is well tolerated and as effective after multiple courses of
      treatment as it is after a single course. There is also clinical evidence that
      prolonged use of sodium hyaluronate (MW 500-730 kDa) may significantly decrease
      the rate of deterioration of joint structure. Localized severe acute inflammatory
      reactions reported with repeated treatment in some patients are not a class
      effect but may be linked to physicochemical characteristics of hylan-based
      treatment. CONCLUSIONS: Repeat courses of the hyaluronans are safe and effective
      in the treatment of pain associated with OA of the knee.

PMID- 15967688
TI  - Improper use of methodological principles in clinical epidemiology.

PMID- 15967689
TI  - Re: Peri-operative myocardial injury in patients undergoing surgery for critical
      limb ischemia. S.D. Hobbs, M. Yapanis, P.J. Burns, A.B. Wilmink, et al. Eur J
      Vasc Endovasc Surg 29, 301-304 (2005).

PMID- 15967691
TI  - Effect of macrolides on peripheral arterial disease depends on patient selection
      and adequate treatment.

PMID- 15967692
TI  - Juvenile hemochromatosis due to G320V/Q116X compound heterozygosity of
      hemojuvelin in an Irish patient.
AB  - Hemojuvelin (HJV) is a recently discovered gene responsible for 1q-linked
      juvenile hemochromatosis. The majority of mutations characterized in this gene
      are rare and private, except G320V, identified in patients from different
      countries. Here, we report the clinical features and the molecular study of a
      young Irish patient presenting with severe cardiac disease related to iron
      overload. We sequenced the coding region and the exon-intron boundaries of genes
      associated with juvenile hemochromatosis, HAMP and HJV encoding hepcidin and
      hemojuvelin respectively. Two heterozygous HJV mutations were identified: the
      G320V mutation and the new Q116X mutation that cause a premature stop codon in
      the protein. This finding increases the number of mutations identified in HJV
      gene and underlines that the G320V is a recurrent mutation, even in Northern
      Europe.

PMID- 15967694
TI  - Different bronchodilator combinations have similar effects on health status in
      COPD.
AB  - BACKGROUND: The main treatment in COPD consists of bronchodilator agents. As the
      severity of disease increases, combined bronchodilators are preferred in place of
      single agents. Since there is a weak correlation between well being and
      spirometric parameters, additional life quality questionnaires are used.
      OBJECTIVES: The main aim of this study was to investigate whether different
      bronchodilator combinations have similar effects on quality of life measures in
      COPD. METHODS: Sixty male patients with COPD were randomized into three groups.
      After a two-week run-in period, life quality scores were determined using the
      Turkish version of St George's Respiratory Questionnaire (SGRQ). Group 1 was
      given ipratropium + theophylline (IP + THEO); Group 2 formoterol + theophylline
      (FOR + THEO) and Group 3 ipratropium + formoterol (IP + FOR). After a 12-week
      treatment period, symptom, activity and impact scores were again determined.
      RESULTS: When compared with baseline, all component scores and total scores
      improved significantly (Delta total score: 16, 15 and 17 units in Groups I, II,
      and III, respectively), but there was no significant change between groups (p >
      0.05). CONCLUSIONS: According to these results, combined bronchodilator
      treatments have a significant effect on life quality in COPD, but the effects
      were observed to be similar between the three different combinations tested.

PMID- 15967693
TI  - Perinatal lethal phenotype with generalized ichthyosis in a type 2 Gaucher
      disease patient with the [L444P;E326K]/P182L genotype: effect of the E326K change
      in neonatal and classic forms of the disease.
AB  - Gaucher disease, the most common lysosomal storage disorder, encompasses a wide
      spectrum of clinical symptoms. The perinatal lethal form is very rare and is
      considered a distinct form of classic type 2 Gaucher disease. Prominent features
      of the severe perinatal form are hepatosplenomegaly variable, associated with
      hydrops fetalis and ichthyosis. Here, we describe a child who presented
      generalized ichthyosis and died at 25 days of age. Genotype analysis revealed
      compound heterozygosity for the complex allele [L444P;E326K] and mutation P182L,
      described for the first time in this patient. Mutations E326K and L444P were on
      the same chromosome. Expression studies of mutant glucocerebrosidases showed that
      the double mutant allele had lower activity, 8.5% of wild type, in contrast to
      the activity of individual E326K and L444P mutant enzymes, 42.7% and 14.1%,
      respectively. The P182L mutant enzyme showed no glucocerebrosidase activity. A
      revision of the genotypes identified in a series of Spanish patients with type 2
      Gaucher disease showed that the complex allele [L444P;E326K] accounted for 19.2%
      of patient alleles and that homozygosity for this allele or its heterozygosity
      with mutation L444P, or another severe mutation such as P182L, was associated
      with the perinatal lethal presentation of the disease. In contrast, the
      [L444P;E326K] allele was not detected in patients with classic type 2 diagnosed
      when several months old. The high frequency of the E326K substitution observed in
      patients with type 2 as compared to the general population (0.5%) suggests that
      this change may have a modulating negative effect on the clinical condition of
      these Gaucher disease patients when present in combination with mutation L444P.
      The relatively high prevalence of the double mutant allele in Spanish patients
      prompted us to perform a haplotype analysis, using four polymorphic markers,
      which suggest a common origin for this allele. During the mutational analysis of
      the series of type 2 patients, a novel mutation, I260T (c.896T>C), was
      identified.

PMID- 15967695
TI  - The effects of nasal histamine challenge on cough reflex in healthy volunteers.
AB  - The aim of the study was to investigate the effects of nasal histamine on the
      intensity of cough reflex and the effects of intensified nasal breathing
      following the nasal histamine challenge on cough sensitivity (CS) in humans. 20
      volunteers (mean age 23, nonsmokers, no history of nasal or respiratory system
      diseases and atopy) were recruited to the study. Baseline CS was determined in
      all subjects. 2 days later the subjects (n = 20) were challenged with nasal
      histamine (8 mg/ml, 0.1 ml) and the number of coughs was determined after four
      consecutive single-breath inhalations of capsaicin C2 concentration during the
      period of the most intensive nasal symptoms (sneezing, itching of the nose). The
      same capsaicin C2 challenge was performed after nasal saline challenge two days
      later. One week later CS was determined after nasal histamine challenge with
      subsequent 10 min of intensified breathing (5-6 sniff-like aspirations to total
      lung capacity per minute) through the nose and mouth in randomized order in ten
      volunteers, and with a two-day interval between the challenges. The same
      manoeuvres after intranasal saline challenge were performed in volunteers of the
      control group (n = 10). The number of coughs after nasal histamine was
      significantly higher than that after intranasal saline challenge (8(6-10) vs 5(3
      7); p = 0.038(. CS was not significantly different between the baseline challenge
      and challenges after nasal histamine followed by the intensified nasal and mouth
      breathing ((2.21 (1.8-2.62) vs 2.04 (1.57-2.51) vs 2.05 (1.6-2.5) log(10) of
      capsaicin concentration in mumol.l(-1); p = 0.09). CONCLUSIONS: During the period
      of maximum nasal symptoms after nasal histamine challenge the cough response to
      inhaled capsaicin was enhanced. Capsaicin cough sensitivity measured after a 10
      min. intensified nasal breathing after nasal histamine challenge, compared to a
      previous measurement of CS, remain unchanged.

PMID- 15967696
TI  - Structure, gene expression, and evolution of primate glutathione peroxidases.
AB  - Glutathione peroxidases (GPxs) are a family of enzymes that scavenge peroxides
      generated in cells. We carried out molecular cloning for cDNAs of four GPx
      isozymes (GPx-1 through 4) in primate species. The essential residues for the
      function of these isozymes were well conserved. A phylogenetic tree of GPx
      isozymes of primates and other mammals showed that GPx-4 diverged first, followed
      by GPx-3, GPx-2, and GPx-1. Expression of mRNAs for GPx-2 through 4 in various
      tissues of Japanese monkey was analyzed by Northern blot hybridization. GPx-2
      mRNA was detected at 1.7 kb, exclusively in the stomach and small intestine. GPx
      3 mRNA was detected at 1.8 kb, intensively in the kidney and adrenal gland, and
      weakly in the cerebellum, heart, and lung. GPx-4 mRNA was detected at 1.1 kb,
      very intensively in the testis and weakly in lung, heart, and cerebellum. These
      results showed that GPx isozymes were expressed under tissue-specific
      regulations.

PMID- 15967697
TI  - Fish fast skeletal muscle tropomyosins show species-specific thermal stability.
AB  - Tropomyosin (TM) was isolated from the fast skeletal muscle of six fish species,
      whose amino acid sequences of this protein have already been revealed. The
      thermal stability of these TMs was measured by differential scanning calorimetry
      (DSC) and circular dichroism (CD), while the molecular weights were measured by
      mass spectrometry. The results showed clear differences in thermostability among
      these fish TMs, though the identity of amino acid sequences was more than 93.3%.
      Therefore, only a few amino acid substitutions could affect the overall stability
      of the TM molecule. Especially, several residues located on the molecular surface
      were considered to be responsible for such stability difference. In contrast, the
      molecular weights of these TMs as measured by mass spectrometry were higher than
      those calculated from amino acid composition, suggesting the presence of post
      translational modification(s) which could also affect their thermal stability.

PMID- 15967698
TI  - Abnormal prorenin processing in growth hormone deficiency.
AB  - Growth hormone deficiency (GHD) is associated with increased premature
      cardiovascular (CV) mortality. Abnormal cardiac structure and function, including
      autonomic adrenergic dysfunction as detected by heart rate variability analysis,
      have been described in GHD. Abnormal prorenin processing resulting in a reduced
      renin/prorenin ratio has been correlated with cardiac autonomic dysfunction, an
      established risk factor for CV mortality, in diabetic patients. We investigated
      renin/prorenin ratios in untreated GHD patients (n=31) and in a group of GHD
      patients treated with GH (n=23) and compared both groups to a group of 59 normal
      control subjects. The treated GHD group was replaced with GH for a mean duration
      of 49.4+/-6.7 months. The mean renin/prorenin ratios were 0.0765+/-0.0089 in the
      untreated GHD group, 0.113+/-0.018 in the treated GHD group, and 0.304+/-0.029 in
      the control group (P<0.01, untreated GHD or treated GHD vs. normal controls;
      P=NS, untreated GHD vs. treated GHD). These results demonstrate that GHD is
      characterized by abnormal prorenin processing implicating concomitant cardiac
      autonomic adrenergic dysfunction, a risk factor for increased CV mortality. GH
      treatment resulted in a non-significant trend towards normalizing this defect.

PMID- 15967699
TI  - Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227
      patients with Wilson disease.
AB  - Wilson disease (WD) is an autosomal recessive disorder of copper transport. WD
      patients are presenting with a wide range of heterogeneous clinical syndromes
      including hepatic, neurological, or psychiatric presentations. The disease is
      caused by mutations in the ATP7B gene. This study presents the results of
      comprehensive mutation analysis in 227 WD patients from 200 unrelated families
      (173 from Czech Republic and 27 from Slovakia). More than 80% of all mutant
      alleles were identified, using a combination of PCR/RFLP, DGGE, TTGE, DHPLC, and
      sequencing. A total of 40 different mutations and 18 polymorphisms were detected
      on 400 independent mutant chromosomes. The most common molecular defect was
      H1069Q (57% of all 400 studied alleles). Each of the other 39 mutations was
      present in no more than 4% of WD alleles and 23 mutations were found in only one
      WD allele each (0.25%). Thirteen novel mutations were identified, including seven
      missense mutations (L641S, T737R, D918E, T1033S, G1111D, D1271N, and G1355C),
      four small deletions (19_20delCA, 1518_1522del5, 3140delA, and 3794_3803del10),
      and two splice-site mutations (2446-2A>G, 2865+1G>A). We did not find a
      significant correlation between H1069Q homozygosity and age of onset, and
      clinical and biochemical manifestation. Our data provide evidence that the H1069Q
      mutation-the most common molecular defect of the ATP7B gene in the Caucasian
      population-originates from Central/Eastern Europe. Screening of five prevalent
      mutations is predicted to reveal 70% of all mutant alleles presented in WD
      patients. This will provide a good starting point for early clinical
      classification of WD in our population.

PMID- 15967700
TI  - [Rectal cancer: preoperative chemoradiation, a new standard].

PMID- 15967701
TI  - The genetics of muscle atrophy and growth: the impact and implications of
      polymorphisms in animals and humans.
AB  - Much of the vast diversity we see in animals and people is governed by genetic
      loci that have quantitative effects of phenotype (quantitative trait loci; QTLs).
      Here we review the current knowledge of the genetics of atrophy and hypertrophy
      in both animal husbandry (meat quantity and quality), and humans (muscle size and
      performance). The selective breeding of animals for meat has apparently led to a
      few genetic loci with strong effects, with different loci in different animals.
      In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with
      few "major" loci identified to date, although this is likely to change in the
      near future. We describe how the same phenotypic traits we see as positive,
      greater lean muscle mass in cattle or a better exercise results in humans, can
      also have negative "side effects" given specific environmental challenges. We
      also discuss the strength and limitations of single nucleotide polymorphisms
      (SNP) association studies; what the reader should look for and expect in a
      published study. Lastly we discuss the ethical and societal implications of this
      genetic information. As more and more research into the genetic loci that dictate
      phenotypic traits become available, the ethical implications of testing for these
      loci become increasingly important. As a society, most accept testing for genetic
      diseases or susceptibility, but do we as easily accept testing to determine one's
      athletic potential to be an Olympic endurance runner, or quarterback on the high
      school football team.

PMID- 15967702
TI  - Epstein-Barr virus encoded latent membrane protein 1 modulates nuclear
      translocation of telomerase reverse transcriptase protein by activating nuclear
      factor-kappaB p65 in human nasopharyngeal carcinoma cells.
AB  - Sustained proliferation of cancer cells requires that telomerase maintain
      chromosomal stability and prolong telomere length-regulated cell replication.
      Human telomerase reverse transcriptase (hTERT), the human telomerase catalytic
      subunit, and also the key determinant of the enzymatic activity of human
      telomerase, is regulated both at the transcriptional level and via
      phosphorylation and translocation. In this study, we show that latent membrane
      protein 1 (LMP1), the principal oncoprotein of Epstein-Barr virus (EBV),
      modulates telomerase activity by inducing the direct binding of hTERT to nuclear
      factor kappaB (NF-kappaB) p65 and translocation of both proteins from the
      cytoplasm to the nucleus in nasopharyngeal carcinoma cells (NPC). Conversely, a
      NF-kappaB nuclear translocation inhibitor, (benzylcarbonyl)-Leu-Leu
      phenylalaninal (Z-LLF-CHO), and a dominant negative mutant of inhibitor of
      NFkappaB (IkappaBalpha), can block LMP1-induced hTERT nuclear translocation.
      These studies suggest a novel function of LMP1 and confirm that NF-kappaB plays
      an important role in regulating the activation and nuclear translocation of
      telomerase in NPC cells.

PMID- 15967703
TI  - Chemokines provide the sustained inflammatory bridge between innate and acquired
      immunity.
AB  - In this review we focus on the role of chemokines in discreet areas of innate
      immunity and demonstrate that chemokines are key participants to not only the
      early inflammatory response to a foreign agent, but important to the sustained
      immune reaction. Our studies support the concept that a concerted and interactive
      innate and acquired immune reaction is key for an automatic, dynamic, sustained,
      and regulated response toward clearing foreign stimuli. It is imperative that the
      in vivo concept of innate and acquired immunity be considered a continuum of a
      global assault on a foreign agent and not as modes, which are independent of one
      another.

PMID- 15967705
TI  - Is emotion regulation self-regulation?

PMID- 15967706
TI  - Nanovector therapeutics.
AB  - An ideal injected therapeutic drug would travel through the vasculature, reach
      the intended target at full concentration, and there act selectively on diseased
      cells and tissues only, without creating undesired side effects. Unfortunately,
      even the best current therapies fail to attain this ideal behavior, by a wide
      margin. A primary reason is the fact that the target recognition abilities of the
      current therapeutics molecules are quite limited. Furthermore, the natural
      defenses of the body present a sequence of formidable obstacles on the drug's
      pathway to the intended lesion. Requiring any molecule to have sufficient
      therapeutic efficacy, target recognition specificity, as well as all of the tools
      required to bypass multiple biological barriers is probably unrealistic. A
      different approach is to decouple the problem (i.e. employ the drug molecules for
      their therapeutic action only, and deliver them to the intended site by vectors
      that can be preferentially concentrated at desired body locations through the
      concurrent action of multiple targeting mechanisms). These vectors must also be
      large enough to comprise all the requirements for the evasion of the body
      defenses, while still sufficiently small so as not to create undesired blockages
      of even the smallest of blood vessels - and thus, by definition,
      nanotechnological.

PMID- 15967707
TI  - The vibrational spectra of (CH3)3SiX (S=H, F, Br) molecules, revisited
      Transferable scale factor sets for methylsilane derivatives.
AB  - The joint experimental and theoretical study of the vibrational spectra of the
      molecular series (CH3)3SiX (with X=H, F and Br) is carried out. Data from newly
      recorded IR and Raman spectra for the bromo derivative, experimental data
      obtained previously for the remaining species, DFT theoretical calculations and
      the use of the SQMFF procedure have allowed us to propose common patterns and to
      unify criteria in their assignment. In addition, two sets of averaged scale
      factors for the B3LYP force field obtained with two different basis sets (6-31G*
      and DZP+diff) have been proposed for the common bulky moiety of that molecular
      series. These parameters were used successfully in order to reproduce the
      frequency of the bands assigned to the (CH3)3Si- group in the vibrational spectra
      of the corresponding silanolic and methoxy derivatives, i.e., trimethylsilanol
      and methoxytrimethylsilane, proving their transferability.

PMID- 15967708
TI  - Stand-off Raman detection using dispersive and tunable filter based systems.
AB  - Small, transportable Raman systems are being developed for stand-off Raman
      measurements at intermediate ranges (e.g. <20 m) for planetary measurements. Four
      variations of stand-off Raman systems are described that use a small telescope
      for light collection that is either fiber-optic or lens-coupled to a detection
      system. The performance of an acousto-optic tunable filter for wavelength
      selection and spectral imaging is tested by comparing signal-to-noise ratio and
      throughput to similar measurements using a conventional spectrograph, and by
      measuring a variety of organic and inorganic mineral samples at distances up to
      15 m. We also determine optimal ICCD gate widths for acquiring remote Raman
      spectra under high ambient light conditions.

PMID- 15967709
TI  - Metal-water interactions and hydrogen bonding in dittmarite-type compounds
      M'M''PO4.H2O (M'=K+, NH4+; M''=Mn2+, Co2+, Ni2+). Correlations of IR
      spectroscopic and structural data.
AB  - The vibrational behavior of the uncoupled nu(OD) modes and of the water
      librations in dittmarite-type compounds M'M''PO4.H2O (M'=K+, NH4+; M''=Mn2+,
      Co2+, Ni2+) is analyzed in terms of the influence of two types of metal-water
      interactions (M+-H2O and M2+-H2O), the hydrogen bonding and the repulsion
      potential of the lattices. The M+-H2O interaction is found to be the main factor,
      which influences nuOD. The strong K+-H2O interaction weakens in a higher degree
      the intramolecular O-H bonds than the corresponding M2+-H2O interactions (M2+=Mn,
      Co, Ni). As a result nuOD is shifted to lower wavenumbers in the potassium series
      than in ammonium one, irrespective of the synergetic effect of M2+, the hydrogen
      bond lengths and the repulsion potential of the lattices. The analysis of the
      spectroscopic data evidences for the dominating influence of the M2+-H2O
      interaction on the wagging mode. The blue shift of nuwag strictly follows the
      increasing synergetic effect of M2+, i.e. nuM'/Mn<nuM'/Co<nuM'/Ni, in all cases,
      irrespective of the strength of the M+-H2O interactions, the hydrogen bond
      lengths and the higher repulsion potential of the K-lattices. The rocking mode is
      insensitive to the replacement of the M2+ ions. Some relations between the
      spectroscopic and structural data are given.

PMID- 15967710
TI  - GEMS: a system for automated cancer diagnosis and biomarker discovery from
      microarray gene expression data.
AB  - The success of treatment of patients with cancer depends on establishing an
      accurate diagnosis. To this end, we have built a system called GEMS (gene
      expression model selector) for the automated development and evaluation of high
      quality cancer diagnostic models and biomarker discovery from microarray gene
      expression data. In order to determine and equip the system with the best
      performing diagnostic methodologies in this domain, we first conducted a
      comprehensive evaluation of classification algorithms using 11 cancer microarray
      datasets. In this paper we present a preliminary evaluation of the system with
      five new datasets. The performance of the models produced automatically by GEMS
      is comparable or better than the results obtained by human analysts.
      Additionally, we performed a cross-dataset evaluation of the system. This
      involved using a dataset to build a diagnostic model and to estimate its future
      performance, then applying this model and evaluating its performance on a
      different dataset. We found that models produced by GEMS indeed perform well in
      independent samples and, furthermore, the cross-validation performance estimates
      output by the system approximate well the error obtained by the independent
      validation. GEMS is freely available for download for non-commercial use from
      http://www.gems-system.org.

PMID- 15967711
TI  - Use of lactoferrin for chronic hepatitis C.

PMID- 15967712
TI  - Efficacy of argon plasma coagulation for gastric antral vascular ectasia
      associated with chronic liver disease.
AB  - Gastric antral vascular ectasia (GAVE) is a rare cause of chronic
      gastrointestinal bleeding. The aim of this study was to evaluate the relationship
      between GAVE with cirrhotic patients and liver dysfunction, portal hypertension
      and the safety and efficacy of argon plasma coagulation (APC) in treating GAVE
      with cirrhotic patients. Eight cirrhotic patients with the characteristic
      endoscopic findings of GAVE were registered. In this study, APC was performed for
      GAVE in all eight patients. The patients-liver function was classified by Child
      Pugh classification and classifications were: two class A, five class B and one
      class C (mean score: 7.8). Five patients had previously received prophylactic
      endoscopic injection sclerotherapy for esophageal varices and one had esophageal
      varices. Balloon-occluded retrograde transvenous obliteration (B-RTO) for gastric
      varices had been performed in other one patient. Portal hypertensive gastropathy
      (PHG) was recognized in only one case. APC was performed in all eight patients
      and one to three treatment sessions were needed (mean: 1.8 sessions). No
      complications were observed in the initial treatment. During follow-up,
      endoscopies revealed the recurrence of GAVE in two patients requiring further
      treatment by APC (recurrence rate: 25%). After APC treatment, the recurrence of
      GAVE was not observed with endoscopy in the other six patients. The results
      suggest that GAVE is related to severe liver damage and portal hypertension in
      cirrhotic patients. APC is a safe and effective treatment against GAVE.

PMID- 15967713
TI  - Phosphatidylinositol biosynthesis: biochemistry and regulation.
AB  - Phosphatidylinositol (PI) is a ubiquitous membrane lipid in eukaryotes. It is
      becoming increasingly obvious that PI and its metabolites play a myriad of very
      diverse roles in eukaryotic cells. The Saccharomyces cerevisiae PIS1 gene is
      essential and encodes PI synthase, which is required for the synthesis of PI.
      Recently, PIS1 expression was found to be regulated in response to carbon source
      and oxygen availability. It is particularly significant that the promoter
      elements required for these responses are conserved evolutionarily throughout the
      Saccharomyces genus. In addition, several genome-wide strategies coupled with
      more traditional screens suggest that several other factors regulate PIS1
      expression. The impact of regulating PIS1 expression on PI synthesis will be
      discussed along with the possible role(s) that this may have on diseases such as
      cancer.

PMID- 15967714
TI  - Localization and functional interrelationships among cytosolic Group IV, secreted
      Group V, and Ca2+-independent Group VI phospholipase A2s in P388D1 macrophages
      using GFP/RFP constructs.
AB  - P388D(1) cells exposed to bacterial lipopolysaccharide (LPS) mobilize arachidonic
      acid (AA) for prostaglandin synthesis in two temporally distinct pathways. The
      "immediate pathway" is triggered within minutes by receptor agonists such as
      platelet-activating factor (PAF) but only if the cells have previously been
      primed with LPS for 1 h. The "delayed pathway" occurs in response to LPS alone
      over the course of several hours. We have now investigated the subcellular
      localization of both the Group IV cytosolic phospholipase A(2) (cPLA(2)) and the
      Group V secreted PLA(2) (sPLA(2)) during these two temporally distinct routes of
      AA release. We have prepared cells overexpressing fusion proteins of sPLA(2)-GFP
      and cPLA(2)-RFP. In the resting cells, cPLA(2)-RFP was uniformly located
      throughout the cytoplasm, and short-term treatment with LPS did not induce
      translocation to perinuclear and/or Golgi membranes. However, such a
      translocation occurred almost immediately after the addition of PAF to the cells.
      Long-term exposure of the cells to LPS led to the translocation of cPLA(2)-RFP to
      intracellular membranes after 3 h, and correlates with a significant release of
      AA in a cPLA(2)-dependent manner. At the same time period that the delayed
      association of cPLA(2) with perinuclear membranes is detected, an intense
      fluorescence arising from the sPLA(2)-GFP was found around the nucleus in the
      sPLA(2)-GFP stably transfected cells. In parallel with these changes, significant
      AA release was detected from the sPLA(2)-GFP transfectants in a cPLA(2)-dependent
      manner, which may reflect cross-talk between sPLA(2) and cPLA(2). The subcellular
      localization of the Group VIA Ca(2+)-independent PLA(2) (iPLA(2)) was also
      investigated. Cells overexpressing iPLA(2)-GFP showed no fluorescence changes
      under any activation condition. However, the iPLA(2)-GFP-expressing cells showed
      relatively high basal AA release, confirming a role for iPLA(2) in basal
      deacylation reactions. These new data illustrate the subcellular localization
      changes that accompany the distinct roles that each of the three kinds of PLA(2)
      present in P388D(1) macrophages play in AA mobilization.

PMID- 15967715
TI  - The effect of dietary sphingolipids on plasma sphingomyelin metabolism and
      atherosclerosis.
AB  - Sphingomyelin (SM) plays a very important role in cell membrane formation and
      plasma lipoprotein metabolism. All these functions may have an impact on
      atherosclerotic development. To investigate the relationship between SM
      metabolism and atherosclerosis, we utilized a sphingolipid-rich diet to feed LDL
      receptor gene knockout (LDLr KO) mice and studied lipid metabolism and
      atherosclerosis in the mice. After 3 months of a sphingolipid-rich diet, we found
      a significant increase in SM, cholesterol, and SM/phosphatidylcholine (PC) ratio
      (50%, P<0.001; 62%, P<0.01; and 45%, P<0.01, respectively), compared to chow fed
      diet. HDL-lipids were not significantly altered. Non-HDL-SM, non-HDL-C, and non
      HDL-SM/non-HDL-PC ratio were significantly increased (115%, P<0.001; 106%,
      P<0.001; and 106%, P<0.01, respectively). FPLC confirmed the results. SDS-PAGE
      showed an increase of apoB48 and apoB100, but no changes of apoAI. Moreover, we
      found that an SM-rich diet significantly increased atherosclerotic lesion area in
      both root assay and en face assay, compared to chow diet (58,210+/-15,300
      microm(2) vs. 9670+/-2370 microm(2), P<0.001; 5.9+/-3.1% vs. 1.1+/-0.9%,
      P<0.001). These results indicate that the enrichment of sphingolipids in diet has
      proatherogenic properties.

PMID- 15967716
TI  - NLRs join TLRs as innate sensors of pathogens.
AB  - Pathogen-recognition receptors (PRRs) are key components of immune systems and
      are involved in innate effector mechanisms and activation of adaptive immunity.
      Since their discovery in vertebrates, Toll-like receptors (TLRs) have become the
      focus of extensive research that has revealed their significance in the
      regulation of many facets of our immune system. What makes TLRs so central and
      fascinating is their ability to recognize microbes and directly initiate specific
      signal transduction cascades that alert the host defences. In this review, we
      discuss the function and biology of a new family of PRRs, the NACHT-LRRs (NLRs),
      which include both nucleotide-binding oligomerization domains (NODs) and NALPs
      [NACHT-, LRR- and pyrin domain (PYD)-containing proteins], and underline some
      intriguing similarities between NLRs and TLRs that emphasize the role of NLRs as
      a complementary system for host-microbe interactions.

PMID- 15967717
TI  - Control of peripheral T-lymphocyte tolerance in neonates and adults.
AB  - Neonatal life is a unique developmental stage, in which the peripheral T
      lymphocyte pool is evolving in a lymphopenic environment and the freshly
      generated T lymphocytes are extensively migrating through non-lymphoid tissues.
      Here, we emphasize the consequences of neonatal lymphopenia and tissue
      accessibility for T-lymphocyte tolerance induction. We propose that self
      destructive T-lymphocyte responses are prevented in the neonate by limiting
      homeostatic T-lymphocyte expansion and thereby the activation of potentially
      autodestructive memory T lymphocytes. Furthermore, the extensive migration
      through tissues might lead to a dominant form of tolerance in the neonatal phase,
      which is maintained throughout adult life, during which the tissues are no longer
      readily accessible to T lymphocytes. Thus, it is not only dendritic cells that
      are crucial for self-tolerance: neonatal mechanisms are also required.

PMID- 15967718
TI  - Intestinal bacteria and development of the B-lymphocyte repertoire.
AB  - Vertebrates have a large antibody repertoire with diverse antigen specificities,
      poised to react to invading pathogens, such as bacteria, viruses and helminths.
      In some species, microbes such as these are required for development of both
      diverse antibody and B-lymphocyte repertoires. Recent studies demonstrate that B
      lymphocyte expansion, selection and somatic diversification of Ig genes are
      regulated in these species, in part, by the interaction between commensal
      intestinal bacteria and gut-associated lymphoid tissue (GALT). These findings
      indicate that the commensal microbiota can shape the repertoire of peripheral B
      lymphocytes and can potentially influence the health of the host. Here, how the
      interactions between commensal microbiota and lymphoid cells of GALT might affect
      the development of the peripheral B-lymphocyte repertoire is discussed.

PMID- 15967719
TI  - Linking Kaposi virus to cancer-associated cytokines.
AB  - Viruses have evolved elaborate strategies to regulate host gene expression,
      thereby adapting to host stress responses against infection. In a recent report,
      it was shown that a human oncogenic herpesvirus, Kaposi sarcoma herpesvirus,
      activates the p38-MK2 pathway to stabilise cytokine transcripts. Specifically, a
      viral latent protein, kaposin B, binds to and activates MK2, leading to the
      stabilisation of AU-rich element (ARE)-containing mRNAs, which normally have only
      a short lifespan. Although the exact mechanism for p38-MK2 activation remains
      unclear, this study provides a new direction linking viral infection to selective
      mRNA turnover and cytokine biosynthesis.

PMID- 15967721
TI  - Worms can worsen malaria: towards a new means to roll back malaria?
AB  - Recent studies in Africa and Asia indicate that different helminthic infections
      adversely affect the clinical outcome of malaria infections. This suggests that
      helminths can influence the acquisition of immunity against Plasmodium. Worms
      could constitute a confounding factor in the assessment of efficacy of malaria
      control intervention, including vaccine prototypes in clinical trials. These
      observations have fundamental and practical consequences; if the deleterious
      effect of worms on malaria is confirmed, treatment of helminths would offer an
      affordable, strongly effective and novel means to roll back malaria. With this
      article, we hope to induce others to conduct similar studies in different
      regions.

PMID- 15967722
TI  - Fellowship of the rings: the replication of kinetoplast DNA.
AB  - Kinetoplastid protozoa such as trypanosomes and Leishmania are important because
      they cause human disease. These parasites are named after one of their most
      unusual features, a mitochondrial DNA known as kinetoplast DNA (kDNA). Unlike all
      other DNA in nature, kDNA comprises a giant network of interlocked DNA rings with
      a topology resembling that of medieval chain mail. The replication of the kDNA
      network is more complex than previously thought, and the discovery of new
      proteins involved in this process is currently the best approach for illuminating
      the replication mechanism.

PMID- 15967723
TI  - Genetic resistance to malaria in mouse models.
AB  - Murine models have proved to be excellent tools in the support of studies of the
      human genetic bases of malaria resistance and have enabled the mapping of 12
      resistance loci, eight of them controlling parasitic levels and four controlling
      cerebral malaria. Further studies using this method have identified a Pklr
      variant that confers resistance to murine malaria, a result that shows the
      potential of this approach to aid the understanding of mechanisms of disease
      resistance. In the future, the use of murine models for genetic resistance to
      malaria could lead to the identification of relevant genetic factors that control
      this devastating disease.

PMID- 15967724
TI  - Insights into CD4+ memory T cells following Leishmania infection.
AB  - Recent publications by Zaph et al. have highlighted the distinct requirements for
      generating and maintaining different subpopulations of CD4(+) memory T cells
      after infection with Leishmania major in mice. These studies have advanced the
      understanding of the nature of long-lasting immunity to Leishmania and, when
      considered within the context of previous work on both murine and human
      leishmaniasis, will aid the design of effective vaccines.

PMID- 15967725
TI  - Human schistosomiasis and anemia: the relationship and potential mechanisms.
AB  - Although many cross-sectional studies and a small number of randomized controlled
      trials have addressed the relationship between schistosomiasis and anemia, the
      conflicting results make the magnitude of the relationship unclear. In fact, only
      one randomized controlled trial that treated solely for schistosomiasis has
      demonstrated an impact of praziquantel on hemoglobin concentration. The potential
      mechanisms underlying a relationship between schistosomiasis and anemia are also
      unclear. In this article, we discuss four possible mechanisms that might mediate
      this relationship, based on animal and human models, including extra-corporeal
      loss of iron, splenomegaly leading to red blood cell sequestration, autoimmune
      hemolysis and anemia of inflammation.

PMID- 15967726
TI  - What distinguishes malaria parasites from other pigmented haemosporidians?

PMID- 15967727
TI  - Factors and interventions influencing health-related quality of life in patients
      with heart failure: a review of the literature.
AB  - INTRODUCTION: Because of the lack of a cure for patients with chronic heart
      failure (HF), there has been a progressive interest in the use of health-related
      quality of life (Hr-QoL) as complementary end-point to mortality and morbidity.
      AIM: The aim of this review was from a nursing perspective to describe Hr-QoL and
      the influencing factors of Hr-QoL, as well as to identify interventions aimed at
      influencing Hr-QoL in HF patients. METHOD: Medline, Cinahl and PsycInfo databases
      were searched from 1995 to 2004. A total of 58 papers were included. RESULTS: HF
      symptoms and activity status influence Hr-QoL negatively. However, several
      individual characteristics such as personality, gender and age must also be taken
      into consideration because different values might exist regarding what
      constitutes a good Hr-QoL. Nurse led interventions based on education, support
      and exercise can influence Hr-QoL positively. There is also a need of more
      studies about the effects of depression, sleep disturbances, support as well as
      education on Hr-QoL. There is also a need of exercise studies with larger sample
      sizes and older patients in higher NYHA classes. CONCLUSION: Several individual
      factors impact Hr-QoL, therefore, must nursing interventions are individually
      adapted to the patient's resources.

PMID- 15967728
TI  - CpG oligodeoxynucleotides stimulate cord blood mononuclear cells to produce
      immunoglobulins.
AB  - CpG oligodeoxynucleotides (ODNs) stimulate adult B cells leading to cellular
      proliferation and immunoglobulin production. It is unknown if CpG-ODNs similarly
      stimulate neonatal human B cells. Neonates have immature immune responses and are
      poorly responsive to thymus independent antigens such as polysaccharides. We
      determined umbilical cord cells' response to CpG-ODNs. Adult and umbilical cord B
      cells produced similar amounts of IgM (adult 1371 +/- 352 vs. cord 1873 +/- 1084
      ng/ml) in response to CpG-ODN stimulation. Although CpG-ODN was able to stimulate
      adult IgG and IgA production, cord cells produced less IgG (153 +/- 58 vs. 10 +/-
      2.5 ng/ml) and no detectable IgA upon CpG-ODN stimulation. CpG ODN stimulated IgM
      production from adult CD27-negative B cells which may account for their ability
      to stimulate the mostly naive cord B cells. The polyclonal IgM response included
      pneumococcal polysaccharide antigen-specific antibodies. CpG-ODNs may be useful
      as neonatal vaccine adjuvants for polysaccharide antigens that are otherwise non
      immunogenic.

PMID- 15967729
TI  - Toward a gene therapy for dominant disease: validation of an RNA interference
      based mutation-independent approach.
AB  - The intragenic heterogeneity encountered in many dominant disease-causing genes
      represents a significant challenge with respect to development of economically
      viable therapeutics. For example, 25% of autosomal dominant retinitis pigmentosa
      is caused by over 100 different mutations within the gene encoding rhodopsin,
      each of which could require a unique gene therapy. We describe here an RNA
      interference (RNAi)-based mutation-independent approach, targeting as an example
      murine rhodopsin. Native transcripts are suppressed by a single RNAi molecular
      species, whereas transcripts from replacement genes engineered at degenerate
      third-codon wobble positions are resistant to suppression. We demonstrate
      suppression of murine rhodopsin transcript by up to 90% with full concomitant
      expression of replacement transcript and establish the validity of this approach
      in cell culture, retinal explants, and mouse liver in vivo.

PMID- 15967730
TI  - Stress echocardiography is superior to exercise ECG in the risk stratification of
      patients presenting with acute chest pain with negative Troponin.
AB  - OBJECTIVE: To compare exercise electrocardiography (ExECG) and stress
      echocardiography (SE) in the risk stratification of patients presenting to
      hospital with cardiac-sounding chest pain, non-diagnostic ECGs and negative
      cardiac Troponin. METHODS: Patients presenting with acute chest pain were
      prospectively randomised to early ExECG or SE. A post-test likelihood of CAD was
      determined by the pre-test likelihood and the result of the stress test. Patients
      with a low post-test likelihood of CAD were discharged; those with a high post
      test probability were considered for coronary angiography. All others were
      managed according to standard hospital protocols. RESULTS: A total of 302
      patients underwent either ExECG or SE. SE identified significantly more patients
      with a low post-test probability of CAD (80% vs 31%, p<0.0001) and significantly
      fewer patients with an intermediate post-test likelihood of CAD compared to ExECG
      (3% vs 47%; p<0.0001). Significantly fewer patients undergoing SE were referred
      for further tests to exclude or refute the diagnosis of CAD (16% vs 52%;
      p<0.0001). In total, 36 (12%) had flow limiting CAD demonstrated by coronary
      angiography. Significant CAD was seen in fewer patients with a positive ExECG
      than with a positive SE (56% vs 84% (p=0.12)). Event rates were low for both
      modalities in patients with low post-test probability (3.5% for SE vs 5.1% for
      ExECG; p=ns) though the number of patients identified as low risk was higher if
      SE was performed. CONCLUSION: Despite negative cardiac Troponin, 12% of patients
      with acute chest pain had significant CAD. SE is superior to ExECG in
      discriminating between those patients with a low and intermediate risk of CAD and
      correctly identified patients with significant CAD, as well as conferring an
      excellent prognosis in those considered low risk. SE significantly reduces the
      requirement for further tests to diagnose CAD compared to ExECG.

PMID- 15967731
TI  - Feature selection in Bayesian classifiers for the prognosis of survival of
      cirrhotic patients treated with TIPS.
AB  - The transjugular intrahepatic portosystemic shunt (TIPS) is a treatment for
      cirrhotic patients with portal hypertension. A subgroup of patients dies in the
      first 6 months and another subgroup lives a long period of time. Nowadays, no
      risk factors have been identified in order to determine how long a patient will
      survive. An empirical study for predicting the survival rate within the first 6
      months after TIPS placement is conducted using a clinical database with 107 cases
      and 77 variables. Applications of Bayesian classification models, based on
      Bayesian networks, to medical problems have become popular in the last years.
      Feature subset selection is useful due to the heterogeneity of the medical
      databases where not all the variables are required to perform the classification.
      In this paper, filter and wrapper approaches based on the feature subset
      selection are adapted to induce Bayesian classifiers (naive Bayes, selective
      naive Bayes, semi naive Bayes, tree augmented naive Bayes, and k-dependence
      Bayesian classifier) and are applied to distinguish between the two subgroups of
      cirrhotic patients. The estimated accuracies obtained tally with the results of
      previous studies. Moreover, the medical significance of the subset of variables
      selected by the classifiers along with the comprehensibility of Bayesian models
      is greatly appreciated by physicians.

PMID- 15967732
TI  - To err is not entirely human: complex technology and user cognition.

PMID- 15967733
TI  - Effects of budesonide and N-acetylcysteine on acute lung hyperinflation,
      inflammation and injury in rats.
AB  - Leukocyte activation and production of inflammatory mediators and reactive oxygen
      species are important in the pathogenesis of lipopolysaccharide (LPS)-induced
      acute lung injury. The present study investigated acute lung hyperinflation,
      edema, and lung inflammation 4 h after an intratracheal instillation of LPS (0.5,
      2.5, 5, 10, 50, 100, 500, 1000, and 5000 microg/ml/kg). Effects of budesonide, an
      inhaled anti-inflammatory corticosteroids, and N-acetylcysteine (NAC), an
      antioxidant, were evaluated in Wistar rats receiving either low (2.5
      microg/ml/kg) or high (50 microg/ml/kg) concentrations of LPS. This study
      demonstrates that LPS in a concentration-dependent pattern induces acute lung
      hyperinflation measured by excised lung gas volume (25-45% above control), lung
      injury indicated by increased lung weight (10-60%), and lung inflammation
      characterized by the infiltration of leukocytes (40-14000%) and neutrophils (80
      17000%) and the production of cytokines (up to 2700%) and chemokines (up to 350%)
      in bronchoalveolar lavage fluid (BALF). Pretreatment with NAC partially prevented
      tumor necrosis factor alpha (TNFalpha) production induced by the low
      concentration of LPS, while pretreatment with budesonide totally prevented the
      increased production of TNFalpha, interleukin (IL)-1beta, IL-6, and monocyte
      chemoattractive protein (MCP)-1 after LPS challenge at both low and high
      concentrations. Budesonide failed to prevent BALF levels of macrophage
      inflammatory protein (MIP)-2 and cytokine-induced neutrophil chemoattractant 1
      (GRO/CINC-1) as well as lung hyperinflation induced by both low and high
      concentrations of LPS. Pretreatment with budesonide totally prevented the
      formation of lung edema at the low concentration of LPS and had partial effects
      on acute lung injury and leukocyte influx at the high concentrations. Thus, our
      data indicate that therapeutic effects of budesonide and NAC are dependent upon
      the severity of the disease.

PMID- 15967734
TI  - Preface.

PMID- 15967735
TI  - Acute renal failure in CF patients chronically infected by the Liverpool epidemic
      Pseudomonas aeruginosa strain (LES).
AB  - Although acute renal failure has been described in children with CF in relation
      to intravenous aminoglycoside use, there are no reports in the adult CF
      literature. We describe 8 cases of acute renal failure in adult CF patients, all
      occurring during the use of intravenous aminoglycosides for the treatment of
      pulmonary exacerbations with an epidemic multi-resistant Pseudomonas aeruginosa
      strain. Potential contributory factors are discussed. These cases demonstrate
      another complication of infection by epidemic Pseudomonas strains in CF, and
      confirm the need for effective segregation policies to prevent this.

PMID- 15967736
TI  - The role of airway epithelium and blood neutrophils in the inflammatory response
      in cystic fibrosis.
AB  - Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance
      regulator (CFTR) gene, which accounts for the cAMP-modulated chloride conductance
      of airway epithelial cells. CFTR also regulates other membrane proteins like the
      negative regulation of the amiloride-sensitive epithelial sodium channel (ENaC).
      Mutations in the CFTR gene lead to hyperabsorption of sodium chloride and a
      reduction in the periciliary salt and water content which leads to impaired
      mucociliary clearance. It seems that a lack of functional CFTR leads to abnormal
      function of the NF-kappaB pathway in submucosal gland cells, causing an increased
      production of pro-inflammatory cytokines and the chemokine IL-8, and a pro
      inflammatory environment. CFTR is also expressed in neutrophils and several
      neutrophil functions like cytokine production, migration, phagocytosis and
      apoptosis seem altered in CF. In this review we describe the role of airway
      epithelium and blood neutrophils in the viscious circle of inflammation and
      infection seen in CF.

PMID- 15967737
TI  - Assessment of lung microstructure with magnetic resonance imaging of
      hyperpolarized Helium-3.
AB  - Magnetic resonance imaging of the apparent diffusion coefficient (ADC) of
      hyperpolarized Helium-3 is a new technique for probing pulmonary microstructure
      in vivo. The aim of this study was the assessment of potential sources of
      systematic errors of the ADC measurement. The influence of macroscopic motion was
      determined by measurements at two different delays after initiating the breath
      hold, and before and after cardiac arrest. An intercentre comparison was
      performed in two age- and lung function-matched groups of lung-healthy volunteers
      at two research sites. Moreover, measurements of diffusion anisotropy were
      performed. We found no dependency of the ADC as a function of the delay after
      stop of inspiration. The influence of cardiac motion was less than 10%. In the
      intercentre comparison study, an excellent agreement between the two sites was
      found. First measurements of the diffusion tensor of intrapulmonary Helium-3 are
      shown.

PMID- 15967738
TI  - Proliferation-dependent pattern of expression of a dihydrofolate reductase
      thymidylate synthase gene from Daucus carota.
AB  - The pattern of expression of a carrot dhfr-ts gene was evaluated in different
      plant organs, in somatic embryos, and in hypocotyl explants induced to
      dedifferentiate in vitro by the addition of the synthetic auxin 2,4
      dichorophenoxyacetic acid. The promoter of this gene was also placed upstream of
      a uidA (GUS) reporter gene and, using biolistic and protoplasts transient
      expression assays, was shown to drive a particularly high level of expression in
      actively growing suspension cells. The results from these expression analyses
      combined with the presence of putative cell cycle-related cis-acting elements in
      the dhfr-ts promoter, strongly point to a cell division-dependent expression of
      this gene.

PMID- 15967739
TI  - A higher concentration of an antigen within the nucleolus may prevent its proper
      recognition by specific antibodies.
AB  - Transient transfection of HeLa cells with a plasmid encoding the full-length
      human fibrillarin fused to a green fluorescent protein (GFP) resulted in two
      major patterns of intensity of the nucleolar labeling for the chimeric protein:
      weak and strong. Both patterns were maintained in fibrillarin-GFP expressing
      cells after fixation with formaldehyde. When the fixed fibrillarin-GFP expressing
      cells were used for immunolabeling with antibodies to fibrillarin, only the
      nucleoli with a weak GFP-signal became strongly labeled, whereas those with the
      heavy signals were only lightly stained, if at all. A similar pattern was
      observed if the cells were immunolabeled with antibodies to GFP. These
      observations suggest that an increase in antigen accumulation within the
      nucleolus, which could take place under various physiological or experimental
      conditions, could prevent the antigen from being recognized by specific
      antibodies. These results have implications regarding contradictory data on
      localization of various nucleolar antigens obtained by conventional
      immunocytochemistry.

PMID- 15967740
TI  - Distribution and frequency of endocrine cells in the pancreas of the ddY mouse:
      an immunohistochemical study.
AB  - The regional distribution and frequency of pancreatic endocrine cells in ddY mice
      were studied by an immunohistochemical (peroxidase anti-peroxidase; PAP) method
      using four types of specific antisera against insulin, glucagon, somatostatin and
      human pancreatic polypeptide (hPP). In the pancreatic islets, most of insulin
      immunoreactive (IR) cells were located in the central portion. Most of glucagon-
      and somatostatin-IR cells were observed in peripheral regions although a somewhat
      smaller number of cells were also located in the central regions. HPP-IR cells
      were randomly distributed throughout the entire islets. In the exocrine pancreas,
      insulin-, glucagon-, somatostatin- and hPP-IR cells were detected; they occurred
      mainly among the exocrine parenchyma as solitary cells. Cell clusters consisted
      of only insulin- or only glucagon-IR cells and were distributed in the pancreas
      parenchyma as small islets. In addition, insulin- and glucagon-IR cells were also
      demonstrated in the pancreatic duct regions. Insulin-IR cells were located in the
      epithelium and sub-epithelial connective tissue regions as solitary cells and/or
      clusters (3-4 cells), and glucagon-IR cells were mainly located in the epithelium
      as solitary cells. Overall, there were 63.89+/-5.39% insulin-, 26.52+/-3.55%
      glucagon-, 7.25+/-2.83% somatostatin- and 1.90+/-0.58% hPP-IR cells. In
      conclusion, some strain-dependent characteristic distributional patterns of
      pancreatic endocrine cells were found in the ddY mouse.

PMID- 15967741
TI  - Lectin histochemistry of the boar bulbourethral glands.
AB  - The present study describes, for the first time, the glycosidic content of boar
      bulbourethral glands using lectin histochemistry. Fourteen horseradish peroxidase
      or digoxigenin-labelled lectins with different carbohydrate specificities were
      used in samples obtained from 3 healthy Landrace boars. The results obtained
      indicate that endpiece and duct cells synthesize and secrete mainly O
      glycoproteins with alpha- and beta-D-N-acetylgalactosamine, beta-D-galactose
      beta(1-->3)-D-N-acetylgalactosamine, D-N-acetylglucosamine and neuraminic acid
      residues. Glycoproteins secreted by bulbourethral glands have a role in the
      protection and lubrication of the urethra. In addition, they may be also involved
      in the regulation of the sperm metabolic activity and in the maintenance of the
      structural integrity of acrosomal and plasma membranes.

PMID- 15967742
TI  - Differential lectin binding patterns in the oviductal ampulla of the horse during
      oestrus.
AB  - We investigated the oligosaccharide sequence of glycoconjugates, mainly
      sialoglycoconjugates, in the horse oviductal ampulla during oestrus by means of
      lectin and pre-lectin methods such as the KOH-neuraminidase procedure to remove
      sialic acid residues and incubation with N-glycosidase F to cleave N-linked
      glycans. Ciliated cells displayed N-linked oligosaccharides throughout the
      cytoplasm. The cilia glycocalyx expressed both N- and O-linked (mucin-type)
      oligosaccharides, both showing a high variety of terminal sequences. In the most
      non-ciliated cells, the whole cytoplasm contained N-linked oligosaccharides with
      terminal alphaGal as well as mucin-type glycans with terminal Forssman
      pentasaccharides. In a few scattered non-ciliated cells, the whole cytoplasm
      displayed sialylated N-linked oligosaccharides with terminal Neu5Ac-GalNAc and O
      linked glycans terminating with neutral and/or alphaGalNAc, Neu5Ac
      alpha2,6Gal/GalNAc, Neu5AcGal beta1,3GalNAc. Supra-nuclear granules, probably
      Golgi zones, of non-ciliated cells showed mainly O-linked glycans rich in sialic
      acid residues. The luminal surface of non-ciliated cells showed N-linked
      oligosaccharides, containing terminal/internal alphaMan/alphaGlc, betaGlcNAc and
      terminal alphaGal, as well as mucin-type oligosaccharides terminating with a
      large variety of either neutral saccharides or sialylated sequences. Apical
      protrusions containing O-linked oligosaccharides with terminal Forssman
      pentasaccharide, Neu5Ac-Gal beta1,4GlcNAc, Neu5Ac-GalNAc were seen in non
      ciliated cells scattered along the epithelium. These findings show the presence
      of sialoglycoconjugates in the oviductal ampulla epithelium of the mare and the
      existence of different lectin binding profiles between ciliated and non-ciliated
      (secretory) cells, as well as the presence of non-ciliated cell sub-types which
      might determine functional differences along the ampullary epithelium of mare
      oviduct.

PMID- 15967743
TI  - Fractal organization of feline oocyte cytoplasm.
AB  - The present study aimed at verifying whether immature cat oocytes with
      morphologic irregular cytoplasm display self-similar features which can be
      analytically described by fractal analysis. Original images of oocytes collected
      by ovariectomy were acquired at a final magnification of 400x with a CCD video
      camera connected to an optic microscope. After greyscale thresholding
      segmentation of cytoplasm, image profiles were submitted to fractal analysis
      using FANAL++, a program which provided an analytical standard procedure for
      determining the fractal dimension (FD). The presentation of the oocyte influenced
      the magnitude of the fractal dimension with the highest FD of 1.91 measured on
      grey-dark cytoplasm characterized by a highly connected network of lipid droplets
      and intracellular membranes. Fractal analysis provides an effective quantitative
      descriptor of the real cytoplasm morphology, which can influence the acquirement
      of in vitro developmental competence, without introducing any bias or shape
      approximation and thus contributes to an objective and reliable classification of
      feline oocytes.

PMID- 15967744
TI  - Characterization of glial fibrillary acidic protein and astroglial architecture
      in the brain of a continuously growing fish, the rainbow trout.
AB  - Unlike mammals, some fish, including carp and trout, have a continuously growing
      brain. The glial architecture of teleost brain has been intensively studied in
      the carp and few data exist on trout brain. In this study, using immunoblotting
      we characterized the topographic distribution of glial fibrillary acidic protein
      (GFAP) in larval and adult rainbow trout brain and studied by
      immunohistochemistry the distribution and morphology of GFAP-immunoreactive cell
      systems in the rainbow trout hindbrain and spinal cord. Immunoblotting yielded a
      double band with an apparent molecular weight of 50-52 kDa in the spinal cord
      homogenate in the trout larval and adult stages. In the adult hindbrain and
      forebrain, our antibody cross reacted also with a second band at a higher
      molecular weight (90 kDa). Because the forebrain contained this band alone the
      two brain regions might contain two distinct isoforms. Conversely, the larval
      total brain homogenate contained the heavy 90 kDa band alone. Hence the heavy
      band might be a GFAP protein dimer or vimentin/GFAP copolymer reflecting nerve
      fiber growth and elongation, or the two isoforms might indicate two distinct
      astroglial cell types as recently proposed in the zebrafish. In sections from
      trout hindbrain and spinal cord the antibody detected a GFAP-immunoreactive glial
      fiber system observed in the raphe and in the glial septa separating the nerve
      tracts. These radial glia fibers thickened toward the pial surface, where they
      formed glial end feet. The antibody also labeled perivascular glia around blood
      vessels in the white matter, and the ependymoglial plexus surrounding the
      ventricular surface in the grey matter. Last, it labeled round astrocytes. The
      GFAP-immunoreactive glial systems had similar distribution patterns in the adult
      and larval spinal cord suggesting early differentiation.

PMID- 15967745
TI  - PACAP in developing sensory and peripheral organs of the zebrafish, Danio rerio.
AB  - The anatomical distribution of PACAP-like immunoreactivity was investigated in
      sensory and peripheral organs of the zebrafish, Danio rerio, during the
      pharyngula, hatching and larval periods, by using indirect immunofluorescence
      methods. First PACAP-like immunoreactive (ir) elements appeared during the
      pharyngula period, at 24 hours post fertilization (hpf), within the most
      superficial layer of the retina and the dorsal aorta. At 48 hpf, additional ir
      cells were found in the olfactory placode and esophagus. At 72 hpf (hatching
      period), PACAP-like immunoreactivity was first detected in the ganglion cell
      layer of the retina, the otic sensory epithelium, pharyngeal arches, swim bladder
      and pancreatic progenitor cells. During day 5 of larval development, new groups
      of ir cells appeared in the liver, whereas no ir elements were observed in the
      olfactory placode. Subsequently, at day 13 of larval development, additional ir
      elements were found for the first time in some gut epithelial cells while those
      previously observed in the retina and otic sensory epithelium were absent. The
      transient expression of PACAP-like ir material in sensory organs suggests that
      the peptide could be implicated in neurotrophic activities and neurosensorial
      connections in the migration and/or differentiation processes. The appearance of
      PACAP-like ir elements in peripheral organs at different developmental stages,
      indicates that this peptide could be involved in the control of more specific
      functions as soon as these peripheral structures begin to operate.

PMID- 15967746
TI  - Swiss mice CD1 fed on mussels contaminated by okadaic acid and yessotoxins:
      effects on thymus and spleen.
AB  - The toxicity of okadaic acid (OA) and yessotoxins (YTXs) was studied in mice
      orally fed on (i) OA (17.80+/-2.41 microg/kg) for 24 h and mouse feed for 24 h;
      (ii) OA (17.2+/-2.13 microg/kg) plus YTXs (1.30+/-0.12 mg/kg) for 24 h and mouse
      feed for 24 h; (iii) OA (18.88+/-1.86 microg/kg) plus YTXs (1.45+/-0.12 mg/kg)
      for 24 h. After toxin treatments the thymus and spleen were examined. More severe
      morpho-functional modifications were found in the thymus, which presented
      atrophy, a significant depletion in the lymphoid compartment and angiogenesis. In
      spite of the impairment, a number of inflammatory cells, reactive to anti
      cytokine antibodies, were recruited. Moreover, greater expression of matrix
      metalloproteinase-9, particularly in cells located near new blood vessels, was
      observed. Thymus injury was still observed after 48 h. Histopathological changes
      to the spleen were more evident in mice orally treated for 24 h and immediately
      sacrificed. The organ showed a significant loss of volume and a fibrous component
      invaded regions involved in immune functions. In white pulp the marginal zones
      were reduced, lymphoid nodules contained large germinal centres and the
      periarteriolar lymphoid sheaths showed cellular depletion. An inflammatory cell
      response was activated by the recruitment of granulocytes, an increased number of
      active macrophages and increased immunoreactivity to cytokines. Unlike in the
      thymus, some evidence of recovery was seen in the spleen. The data suggest that
      low oral doses of OA alone or OA plus YTXs are able to provoke immunostimulation
      and systemic immunotoxicity, thus also indicative of tumorigenic properties.

PMID- 15967747
TI  - Tissue damage after acute intoxication by polychlorinated biphenyls in
      cockroaches.
AB  - It is common knowledge that polychlorinated biphenyls (PCBs) represent a serious
      threat to the health of both vertebrates and invertebrates. As far as the former
      are concerned, especially as regards human beings, a broad literature describes
      the direct and indirect effects induced by the PCBs on their systems and organs.
      Among invertebrates, the information available is mostly related to arthropods
      and is, however, very scarce. The aim of this work was to evaluate the effects of
      polychlorinated biphenyls (PCBs) on tissues and organs of individuals belonging
      to a species of Blattaria (Blattella germanica) treated with various doses of
      this toxic material. The pathologies found became more serious as the dosage
      increased and were present throughout the entire digestive system, in the fat
      body and in the male gonads: in these areas cell and tissue breakdown and
      severely damaged spermiogenesis were observed. In particular, the testes,
      Malpighian tubules and fat body accumulated an amorphous basophilic PAS-positive
      substance. Furthermore, the NOS-dependent NADPH diaphorase activity pattern in
      the retina and optic lobes was more evident in the treated than in the control
      insects.

PMID- 15967748
TI  - Detection of non-papillary, non-invasive transitional cell G1 carcinoma as
      revealed by increased DNA instability and other cancer markers.
AB  - The method to reveal DNA-instability as demonstrated by immunohistochemical
      staining with anti-cytidine antibody after acid hydrolysis (DNA-instability test)
      was used as a marker of malignancy. The test was applied to paraffin-embedded
      sections taken from 15 urinary bladders, renal pelvic cavities, and ureters
      bearing multiple carcinoma in situ (CIS) and totally 31 papillary urothelial
      cancers. The serial sections of the same tissues were also subjected to
      immunohistochemical staining for PCNA, p53, DFF45, and VEGF. The DNA-instability
      test was positive in 100% cancer lesions irrespective of the grades, and
      apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions
      also showed the areas with clones positively stained with DNA-instability
      testing, and the percent numbers of positive areas in them were 28.3%, 37.7%, and
      61.5%, respectively. These clones, which were present in apparently normal
      urothelium and in hyperplastic and dysplastic urothelial lesions, showed higher
      percent values of PCNA-positive-cells, in comparison to the values estimated in
      the areas with negatively stained DNA-instability testing, and the former values
      were statistically not different from those in carcinoma lesions. Furthermore,
      the percent numbers of areas positive for p53, DFF45, and VEGF, with positive DNA
      instability testing were also much higher than those with negative DNA
      instability testing in apparently normal urothelium, and hyperplastic and
      dysplastic urothelial lesions, and the former values were again comparable to
      those in cancer lesions with no statistical differences. These clones were
      regarded as already being malignant and should be the direct precursors of
      progressed cancer lesions. They will make progression through two different
      pathways, one to papillary non-invasive G1 cancers by neovascularization induced
      by paracrine secretion of VEGF, and another to flat CIS G2 without secretion of
      VEGF; thus the clones should be regarded as non-papillary, non-invasive Gl TCC,
      or CIS G1. It should be always taken into account that the probability for
      apparently normal urothelium, and hyperplastic and dysplastic urothelial lesions
      to contain cancer clones, will be high already, especially in tumor-bearing
      bladders.

PMID- 15967749
TI  - New tetrachromic VOF stain (Type III-G.S) for normal and pathological fish
      tissues.
AB  - A new VOF Type III-G.S stain was applied to histological sections of different
      organs and tissues of healthy and pathological larvae, juvenile and adult fish
      species (Solea senegalensis; Sparus aurata; Diplodus sargo; Pagrus auriga;
      Argyrosomus regius and Halobatrachus didactylus). In comparison to the original
      Gutierrez VOF stain, more acid dyes of contrasting colours and
      polychromatic/metachromatic properties were incorporated as essential
      constituents of the tetrachromic VOF stain. This facilitates the selective
      staining of different basic tissues and improves the morphological analysis of
      histochemical approaches of the cell components. The VOF Type III -6.5 stain is
      composed of a mixture of several dyes of varying size and molecular weight
      (Orange G<acid Fuchsin<Light green<Methyl Blue<Fast Green), which are used
      simultaneously, and it enables the individual tissues to be selectively
      differentiated and stained. Muscle fibers, collagen, reticulin and elastin
      fibers, erythrocytes, cartilage, bone, mucous cells, oocytes and larvae were
      selectively stained and differentiated. Dyes with small size and molecular weight
      (i.e Orange G), penetrate all tissue structures rapidly, but are only tightly
      retained in densely textured tissues (i.e erythrocytes). Methyl Blue is an
      interesting triarylmethane dye (large size and molecular weight), which is
      incorporated in this new VOF tetrachrome stain, and acquires histochemical
      significance when used at acid pH (2.8) because collagen and reticulin fibers, as
      well basophilic and metachromatic substances (strongly ionized sulphated
      glycoconjugates) can be identified. Muscle tissues show an evident green colour
      (Fast Green or Light Green affinities), even those isolated and/or diffuse muscle
      fibers present in the digestive submucosa layer. Connective tissues showed a
      specific and strong blue colour (Methyl Blue affinity) or mixed blue-red staining
      (Methyl Blue and Acid Fucshin affinities). Very noticeable is the staining of the
      mucous cells, as well as the hyaline capsule of the viral lymphocystic cells,
      which were stained blue-purple (carboxylated and/or strongly ionized sulphated
      groups). Cartilaginous tissues showed a blue or purple (Methyl Blue affinity)
      staining, and a specific red colour (Acid Fucshin affinity) was evident during
      calcification or in bone structures (i.e skeleton, fins, gills, teeth).

PMID- 15967750
TI  - Abstracts of the XVII Meeting on "ADP-Ribosylation Processes", Rome, Italy, 17-18
      December 2004.

PMID- 15967751
TI  - Dual-task-related gait changes in the elderly: does the type of cognitive task
      matter?
AB  - Dual-task-related gait changes among older adults while they perform spoken
      verbal tasks have been reported frequently. The authors examined whether the type
      of walking-associated spoken verbal task matters for dual-task-related gait
      changes in 16 older adults classified as transitionally frail. Mean stride time
      increased significantly when they walked and performed an arithmetic or a verbal
      fluency task compared with when they only walked (p < .001), whereas the
      coefficients of variation increased significantly only when they walked and
      performed the arithmetic task (p = .005) but not the verbal fluency task (p =
      .134). Those findings suggest that stride time variability under a dual-task
      condition depends on the type of walking-associated spoken verbal task.

PMID- 15967752
TI  - Visual search and coordination changes in response to video and point-light
      demonstrations without KR.
AB  - The authors examined the observational learning of 24 participants whom they
      constrained to use the model by removing intrinsic visual knowledge of results
      (KR). Matched participants assigned to video (VID), point-light (PL), and no
      model (CON) groups performed a soccer-chipping task in which vision was occluded
      at ball contact. Pre- and posttests were interspersed with alternating periods of
      demonstration and acquisition. The authors assessed delayed retention 2-3 days
      later. In support of the visual perception perspective, the participants who
      observed the models showed immediate and enduring changes to more closely imitate
      the model's relative motion. While observing the demonstration, the PL group
      participants were more selective in their visual search than were the VID group
      participants but did not perform more accurately or learn more.

PMID- 15967753
TI  - Lateralization of bilateral transfer of visuomotor information in right-handers
      and left-handers.
AB  - The author examined the lateralization of transfer of visuomotor information
      between the right and left hands during unimanual finger-tapping sequences with
      visual feedback. The finger-tapping task consisted of a target peak force of 2 N
      and a target intertap interval of 500 ms. Twenty right-handed and 10 left-handed
      participants performed the motor task, with 3 transfer trials following 3
      practice trials. The author observed positive transfers from the left to the
      right hand for right-handers but the opposite direction of positive transfers for
      left-handers. However, left-handers showed a less variable peak force than right
      handers did. The author discusses left-handers' interhemispheric information
      processing.

PMID- 15967754
TI  - Grip width and the organization of force output.
AB  - The authors investigated the structure of force production and variability as a
      function of grip configuration and width during precision grasping. Variability
      was studied in absolute (standard deviation) and relative (coefficient of
      variation) terms; in addition, the authors used approximate entropy to examine
      regularity. In Experiment 1, the participants (N = 14) used a 2-digit grasp
      (thumb, index), whereas in Experiment 2, the participants (N = 11) used a 3-digit
      grasp (thumb, index, middle). The level and regularity of force increased with
      grip width. The amount of variability was least at narrow grip widths for 2-digit
      grasping and greatest at narrow grip widths for 3-digit grasping. That pattern of
      findings is not necessitated by the mechanical equilibrium of grasping; thus, it
      also reflected adaptive neural reorganization of force output to task demands.

PMID- 15967755
TI  - The use of (symmetry) group theory as a predictive tool for studying bimanual
      coordination.
AB  - Symmetry groups-rules that connect different configurations of a given set of
      components-represent a compact means of coding for effects, a feature that is
      desirable in both model- and theory-building. The present study was designed to
      compare the effects of spatial orientation differences with the various other
      asymmetries (e.g., timing differences, handedness preferences, the direction of
      attention) that are accommodated by current models of bimanual coordination. The
      authors used symmetry groups to predict specific patterns of results. In 2
      experiments, participants (N = 13, Experiment 1; N = 9, Experiment 2) coordinated
      the movements of differently oriented (1 downward and 1 upward) pendulum pairs at
      a low (0.62 Hz) or high (0.82 Hz) movement frequency to establish an in-phase or
      antiphase pattern. Consistent with previous results (P. G. Amazeen, E. L.
      Amazeen, & M. T. Turvey, 1998a), the downward-oriented pendulum tended to lead
      slightly. In contrast to the effects of other bimanual asymmetries, the downward
      oriented pendulum lead was amplified at low frequencies. Although the results
      contradicted the predictions of existing models of bimanual coordination, they
      were consistent with predictions from symmetry group theory. In the discussion,
      the authors focus on the application of symmetry groups to both bimanual
      coordination and other phenomena with more complex symmetric structures.

PMID- 15967756
TI  - Effects of visual and auditory short-term memory tasks on the spatiotemporal
      dynamics and variability of postural sway.
AB  - The authors measured postural sway while participants (N = 20 in each experiment)
      stood on a rigid or a compliant surface, with their eyes open or closed, and
      while they did or did not perform a short-term memory (STM) task. In Experiment
      1, the STM stimuli were presented visually; in Experiment 2, the stimuli were
      presented auditorily. In both experiments, fine-scaled, mediolateral postural
      sway variability decreased as the cognitive load imposed by the STM task
      increased. That effect was independent of support surface and vision
      manipulations. The spatiotemporal profile of postural sway was affected by both
      visual and auditory STM tasks, but to a greater degree by the auditory task. The
      authors discuss implications of the results for theories and models of postural
      control.

PMID- 15967757
TI  - Intermittency of visual information and the frequency of rhythmical force
      production.
AB  - The authors examined the influence of intermittent (40-5,000 ms) visual
      information on the control of rhythmical isometric force output (0.5, 2.0, and
      4.0 Hz) in 10 participants. Force variability decreased as a function of less
      intermittent visual information only in the 0.5- and 2.0-Hz tasks. Vision
      influenced the frequency structure of force output through 0-12 Hz in the 0.5-Hz
      task, but in only the 10.0- to 12.0-Hz range in the 2.0-Hz task and not in the
      4.0-Hz task. The effective use of intermittent visual information in force output
      was mediated by task frequency, and that mediation was reflected in the
      differential emphasis of feedback and feedforward processes over multiple
      timescales of control.

PMID- 15967758
TI  - Estimating the intensity of infection with Schistosoma japonicum in villagers of
      leyte, Philippines. Part I: a Bayesian cumulative logit model. The
      schistosomiasis transmission and ecology project (STEP).
AB  - Intensity profiles for helminths are used to describe population infection
      status, monitor effectiveness of control programs, and provide accurate data to
      validate transmission models. This study aims to accurately predict age/gender
      specific intensity profiles of endemic schistosomiasis japonica infection in the
      Philippines. Poor sensitivity of the Kato-Katz test and large heterogeneity in
      infection levels across villages complicate these predictions. Data from 1,989
      individuals living in three endemic villages were analyzed with a Bayesian
      cumulative-logit model adjusting for nonproportional odds, variation between
      villages, and measurement error. The posterior uncertainty regarding the
      proportion of individuals in each egg category was high compared with that
      estimated using a model ignoring measurement error and villages' heterogeneity.
      The intensity profiles were very different in children less than 7 years old
      compared with older children and adults. This model could easily be adapted to
      other parasitic infections or outcomes where an analysis by category would be
      recommended.

PMID- 15967759
TI  - Early detection of dengue infections using cluster sampling around index cases.
AB  - A two-year study using a cluster investigation method was conducted in West
      Jakarta, Indonesia to demonstrate the detection of dengue cases prior to onset of
      clinical illness. The clusters consisted of family members and neighbors of 53
      hospitalized dengue index cases. Among 785 adult and child volunteers enrolled,
      17 (2.2%) post-enrollment dengue (PED) infections were identified. Eight PED
      cases were asymptomatic and nine were symptomatic. Symptomatic cases included
      eight with dengue fever and one with dengue hemorrhagic fever (DHF) (grade II).
      Among the eight asymptomatic PED cases, viremia was detected in two. Eleven
      volunteers had acute dengue infections at the time of enrollment. Four of the 11
      developed DHF, resulting in a total of five DHF cases detected during the
      investigation. This study design can serve as a benchmark for future
      investigations that seek to define early immunologic events following dengue
      infections that contribute to the development of DHF.

PMID- 15967760
TI  - Antibiotic prescribing in general practice and hospital admissions for
      peritonsillar abscess, mastoiditis, and rheumatic fever in children: time trend
      analysis.

PMID- 15967761
TI  - Fate of biomedical research protocols and publication bias in France:
      retrospective cohort study.
AB  - OBJECTIVES: To describe the fate of protocols approved by the French research
      ethics committees, a national system created by the French 1988 Huriet-Serusclat
      Act; to assess publication bias at a national level. DESIGN: Retrospective cohort
      study. SETTING: Representative sample of 25/48 French research ethics committees
      in 1994. PROTOCOLS: 649 research protocols approved by committees, with follow-up
      information. MAIN OUTCOME MEASURES: Protocols' initial characteristics (design,
      study size, investigator) abstracted from committees' archives; follow-up
      information (rates of initiation, completion, and publication) obtained from
      mailed questionnaire to principal investigators. RESULTS: Completed
      questionnaires were available for 649/976 (69%) protocols. Of these, 581 (90%)
      studies were initiated, 501/581 (86%) were completed, and 190/501 (38%) were
      published. Studies with confirmatory results were more likely to be published as
      scientific papers than were studies with inconclusive results (adjusted odds
      ratio 4.59, 95% confidence interval 2.21 to 9.54). Moreover, studies with
      confirmatory results were published more quickly than studies with inconclusive
      results (hazard ratio 2.48, 1.36 to 4.55). CONCLUSION: At a national level, too
      many research studies are not completed, and among those completed too many are
      not published. We suggest capitalising on research ethics committees to register
      and follow all authorised research on human participants on a systematic and
      prospective basis.

PMID- 15967762
TI  - Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic
      factors? Cluster randomised clinical trial in general practice.
AB  - OBJECTIVE: To compare the effects of a minimal intervention strategy aimed at
      assessment and modification of psychosocial prognostic factors and usual care for
      treatment of (sub)acute low back pain in general practice. DESIGN: Cluster
      randomised clinical trial. SETTING: 60 general practitioners in 41 general
      practices. PARTICIPANTS: 314 patients with non-specific low back pain of less
      than 12 weeks' duration, recruited by their general practitioner. INTERVENTIONS:
      In the minimal intervention strategy group the general practitioner explored the
      presence of psychosocial prognostic factors, discussed these factors, set
      specific goals for reactivation, and provided an educational booklet. The
      consultation took about 20 minutes. Usual care was not standardised. MAIN OUTCOME
      MEASURES: Functional disability (Roland-Morris disability questionnaire),
      perceived recovery, and sick leave because of low back pain assessed at baseline
      and after 6, 13, 26, and 52 weeks. RESULTS: The dropout rate was 8% in the
      minimal intervention strategy group and 9% in the usual care group. Multilevel
      analyses showed no significant differences between the groups on any outcome
      measure during 12 months of follow-up in the whole group or in relevant subgroups
      (patients with high scores on psychosocial measures at baseline or a history of
      frequent or prolonged low back pain). CONCLUSION: This study provides no evidence
      that (Dutch) general practitioners should adopt our new treatment strategy aimed
      at psychosocial prognostic factors in patients with (sub)acute low back pain.
      Further research should examine why our new strategy was not more effective than
      usual care.

PMID- 15967763
TI  - Early psychosocial interventions for low back pain in primary care.

PMID- 15967764
TI  - Erythrocyte aldehyde dehydrogenase activity: lack of association with alcohol use
      and dependence or alcohol reactions in Australian twins.
AB  - AIM: Aldehyde dehydrogenase 1 (ALDH1) has been advocated as a marker of alcohol
      intake. The absence or low levels of ALDH1 may be associated with alcohol-induced
      flushing or other reactions to alcohol in Europeans and therefore, with reduced
      alcohol use. This study tested whether variation in erythrocyte ALDH1 activity
      was associated with alcohol use, alcohol dependence or reactions to alcohol in
      unselected subjects of European descent, and whether variation in ALDH1 activity
      was subject to genetic influences. METHODS: ALDH activity was measured in
      erythrocytes from 677 men and women who had participated in a twin study of
      alcohol use and dependence. RESULTS: There were no significant effects of sex,
      alcohol consumption or alcohol dependence on ALDH activity. Subjects who reported
      reactions to alcohol did not have low activity. Women aged below 45 years had
      lower ALDH activity than men or older women. The heritability of ALDH activity
      was 56% (95% confidence interval = 42-67%). CONCLUSIONS: Previous reports that
      erythrocyte ALDH activity is low in alcoholics were not substantiated in this
      community-based sample. Associations with alcohol reactions were not found. ALDH
      activity varies widely between subjects, largely because of genetic factors.

PMID- 15967765
TI  - Multidrug-resistant Salmonella enterica serotype Senftenberg isolates producing
      CTX-M beta-lactamases from Constantine, Algeria.

PMID- 15967766
TI  - High prevalence of macrolide resistance: not in every country! [Comment on:
      Halpern et al. J Antimicrob Chemother 2005; 55: 748-57].

PMID- 15967767
TI  - In vitro selection of resistance in Pseudomonas aeruginosa and Acinetobacter spp.
      by levofloxacin and ciprofloxacin alone and in combination with beta-lactams and
      amikacin.
AB  - OBJECTIVES: The aim of this study was to evaluate the ability of levofloxacin and
      ciprofloxacin alone and in combination with either ceftazidime, cefepime,
      imipenem, piperacillin-tazobactam or amikacin to select for antibiotic-resistant
      mutants of Pseudomonas aeruginosa and Acinetobacter spp. METHODS: Clinical
      strains of P. aeruginosa (n = 5) and Acinetobacter spp. (n = 5) susceptible to
      all the drugs used in the study were assayed. Development of resistance was
      determined by multi-step and single-step methodologies. For multi-step studies,
      MICs were determined after five serial passages on antibiotic-gradient plates
      containing each antibiotic alone or in combination with levofloxacin or
      ciprofloxacin. Acquisition of resistance was defined as an increase of >or=4-fold
      from the starting MIC. In single-step studies, the frequency of spontaneous
      mutations was calculated after a passage on plates containing antibiotics alone
      and in combinations at concentrations equal to the highest NCCLS breakpoints.
      RESULTS: Serial passages on medium containing single antibiotics resulted in
      increased MICs for each antibiotic; MIC increases were limited by antibiotics in
      combination. A decrease in the number of strains with MICs above the NCCLS
      breakpoints occurred when fluoroquinolones were combined with a second antibiotic
      for both P. aeruginosa and Acinetobacter spp. isolates. Frequencies of mutation
      were higher for antibiotics alone than for combinations. CONCLUSIONS: Use of
      combinations of fluoroquinolones with beta-lactams and amikacin reduces the risk
      for in vitro selection of resistant P. aeruginosa and Acinetobacter spp.

PMID- 15967768
TI  - Nalidixic acid-susceptible, ciprofloxacin-resistant Neisseria gonorrhoeae strain
      in the UK.

PMID- 15967769
TI  - Molecular detection of antibiotic resistance: when and where?
AB  - Antibiotic resistance is a key issue affecting public health, and diagnostic
      bacteriology laboratories are essential for prompt recognition of resistant
      isolates. Determination of susceptibility or resistance using phenotypic tests is
      a 'gold standard' against which newer technologies are compared in terms of
      performance, cost and ease of use. Molecular methods for detecting resistance are
      myriad, and are used widely in academia and in reference laboratories, but
      gaining a significant foothold in diagnostic laboratories is proving more
      difficult. However, if used widely in a diagnostic setting, these techniques
      would impact more directly on patient care and would be valuable infection
      control tools, e.g. by rapidly confirming patients colonized by resistant
      bacteria. The cost of molecular assays may be considered prohibitive, and this is
      compounded by the daunting variety of proprietary platforms available; most
      diagnostic laboratories would prefer to invest their capital and to train their
      staff in a single versatile technology. In a market that has no clear leader,
      many laboratories are understandably reluctant to gamble on making the correct
      choice. If molecular detection of resistance is to achieve wide acceptance,
      manufacturers must broaden the repertoires of their technologies, develop more
      off-the-shelf applications with in-built quality control, and make them suitable
      for laboratory personnel with no specialist expertise in molecular biology.

PMID- 15967770
TI  - Characterisation of beta-globin gene mutations in Malaysian children: a strategy
      for the control of beta-thalassaemia in a developing country.
AB  - beta-thalassaemia major, an autosomal recessive hemoglobinopathy, is one of the
      most common single gene disorders in multi-racial Malaysia. The control of beta
      thalassaemia major requires a multi-disciplinary approach that includes
      population screening, genetic counselling, prenatal diagnosis and the option of
      termination of affected pregnancies. To achieve this objective, the molecular
      characterisation of the spectrum of beta-globin gene mutations in each of the
      affected ethnic groups is required. We studied 88 consecutive unrelated
      individuals and their respective families with beta-thalassaemia (74 beta
      thalassaemia major, 12 HbE-beta-thalassaemia, 2 with HbE homozygotes) and four
      individuals with beta-thalassaemia trait that contributed a total 180 alleles for
      study. Using a 2-step molecular diagnostic strategy consisting of amplification
      refractory mutation system (ARMS) to identify the 8 most common mutations
      followed by other DNA-based diagnostic techniques, a total of 177 (98.3 per cent)
      of the 180 beta-thalassaemia alleles were characterised. One out of 91 (1 per
      cent) of the Chinese alleles, one out of 46 (2.2 per cent) Malay alleles and one
      out of two Indian alleles remained unknown. A 100 per cent success rate was
      achieved in studying the Kadazandusun community in this study. A strategy to
      identify beta-globin gene mutations in Malaysians with beta-thalassaemia is
      proposed based on this outcome.

PMID- 15967771
TI  - Infant feeding practices before implementing alternatives to prolonged
      breastfeeding to reduce HIV transmission through breastmilk in Abidjan, Cote
      d'Ivoire.
AB  - The aim of this study was to describe baseline infant feeding practices in women
      of unknown HIV status in Abidjan, Cote d'Ivoire, before the implementation of
      infant feeding interventions aimed at the prevention of mother-to-child
      transmission of HIV through breastmilk. We conducted a cross-sectional survey in
      March 2000 among 225 mothers attending community-run health facilities with their
      own child for either immunization or weighting. All but two children had ever
      been breastfed, of whom 94 per cent were still being breastfed at 6 months of
      age. Exclusive breastfeeding was not practiced in this population since all women
      had given water to their child, starting in median one day after birth. Moreover,
      20 per cent of the mothers had introduced infant formula in median three weeks
      after delivery. This study provides useful information for planning purposes in
      this urban African population, where exclusive breastfeeding is rare and the use
      of infant formula relatively common.

PMID- 15967772
TI  - Septicemic neonates without lumbar puncture: what are we missing?
AB  - Meningitis is a serious problem in newborn infants and has high mortality and
      frequent neurological sequelae. In neonates, signs and symptoms of serious
      infections are often obscure and clinical examination cannot distinguish
      septicemic babies with or without meningitis. Therefore, lumbar puncture is often
      not done in time and thus diagnosis of meningitis is missed. This study aimed to
      discover the prevalence of meningitis among these cases based on laboratory
      investigation. We prospectively enrolled the blood culture positive septicaemia
      cases which were not labeled as cases of meningitis during routine clinical
      evaluation. Out of 30 septicemic cases, eight (26.7%) had abnormal CSF cytology
      and biochemistry suggestive of meningitis. Among these eight cases, four had
      positive CSF culture; [Klebsiella pneumoniae (n = 3) and Pseudomonas aeruginosa
      (n = 1)], which were similar to the blood isolate of the respective patient. The
      clinical manifestations were similar in both septicemia and meningitis cases.
      Mortality was high among the meningitis cases compared with those having
      septicemia alone (37.5% vs. 13.3%), indicating the need for early diagnosis of
      this disease. Our data confirmed that it is important to do a lumbar puncture,
      along with blood culture, for all suspected septicemia cases.

PMID- 15967773
TI  - Etiologic evaluation in 247 children with global developmental delay at Istanbul,
      Turkey.
AB  - OBJECTIVE: Developmental delay is a common pediatric problem, having a great
      number of underlying causal factors. Etiologic diagnosis is important for
      providing information about pathogenesis, prognosis, recurrence risk and specific
      medical interventions. The aim of this study was to determine the etiologic yield
      and spectrum of a consecutive cohort of global developmentally delayed children.
      METHODS: This retrospective study included all children younger than 5 years of
      age with global developmental delay referred to a single university-based
      ambulatory pediatric neurology clinic for initial evaluation over a 14-month
      period from January 1997. Diagnostic studies consisted of history, physical
      examination, electroencephalography and selected investigations including
      neuroimaging, screening for metabolic disease, karyotype and fragile X testing.
      RESULTS: In the study 247 patients (136 males) with a mean age of 24.2+/-20.3
      months were evaluated. Etiologic diagnosis was determined in 64 per cent of the
      patients classified under the following categories: perinatal complications (21
      per cent), cerebral dysgenesis (18 per cent), chromosomal abnormalities (9 per
      cent), genetic/dysmorphic syndromes (3 per cent), metabolic disorders (4 per
      cent), hypothyroidism (4 per cent), neurocutaneous syndromes (3 per cent),
      intrauterine infection (2 per cent). Etiology was unknown in 36 per cent of the
      patients. Two laboratory tests (neuroimaging and cytogenetic analysis) together
      with the history and physical examination were most helpful in determining the
      etiologic diagnosis. CONCLUSION: This study suggests that optimal management of
      global developmentally delayed children and their family should involve a
      comprehensive evaluation.

PMID- 15967774
TI  - Pollination in Brazilian Syngonanthus (Eriocaulaceae) species: evidence for
      entomophily instead of anemophily.
AB  - BACKGROUND AND AIMS: The reproductive biology of Syngonanthus mucugensis and S.
      curralensis (Eriocaulaceae) was studied in areas of 'campo rupestre' vegetation
      in the Chapada Diamantina, north-eastern Brazil. These species are herbaceous and
      the individuals have a grouped distribution. Their leaves are united in a
      rosette, and their inflorescence is monoecious, of the capitulum type. The
      staminate and pistillate rings mature in a centripetal manner on the capitulum.
      METHODS: A field study was conducted, including observations concerning the
      morphology and biology of the flowers, fruit development, insect visits and
      anemophily, in both S. mucugensis and S. curralensis. Experimental pollinations
      were also carried out to study the mating systems of S. mucugensis. KEY RESULTS:
      Both species flower from June to August. The staminate cycle lasts approx. 7 d,
      and the pistillate cycle from 3 to 4 d, with no temporal overlap between them on
      the same capitulum. The pollen viability of S. mucugensis was 88.6%, and 92.5%
      for S. curralensis. The inflorescences of both species demonstrated ultraviolet
      absorbance, and a sweet odour was detected during both the staminate and
      pistillate phases. No nectar production was ever noted, although nectaries are
      present. Both species were visited by numerous groups of insects, with the
      Diptera being the principal pollinators, especially the species of Syrphidae and
      Bombyliidae. There were secondary pollinators among species of Coleoptera and
      Hymenoptera. There was no evidence of wind pollination. Syngonanthus mucugensis
      is a self-compatible species, and forms fruits by agamospermy at low frequencies.
      CONCLUSIONS: This is apparently the first report for pollination biology and
      mating systems of Eriocaulaceae. Conversely to that stated by some authors,
      entomophily, mainly effected by species of Diptera but also by species of
      Coleoptera and Hymenoptera, is probably the only pollination system in these
      species. In spite of the monoecious inflorescences without overlap of the
      staminate and pistillate phases, geitonogamy may occur in S. mucugensis, as the
      species is self-compatible and different capitula in the same plant at different
      phases is common.

PMID- 15967775
TI  - Hunter-gatherer human nature and health system safety: an evolutionary cleft
      stick?
AB  - The stunning archaeological find of a new species of human dubbed the hobbit,
      formally named Homo floresiensis, is a reminder that humans and hobbits are
      evolved for transient lives, subsisting in an environment radically different
      from that of contemporary societies. Although the problems facing health systems
      are well documented, few scholars have taken an evolutionary-level approach to
      understanding them. By considering the nature of humans as adapted not for modern
      societies but for hunter-gatherer existence, and examining what humans were
      evolved for, new light can be shed on contemporary behaviours exposed by the
      medical inquiries into what is going wrong in acute health systems. Investigation
      of two of these inquiries shows how health professionals under pressure typically
      default to tribal behaviours, have recourse to hierarchies and engage in turf
      protection routines. Those who have conducted studies into iatrogenic harm or
      presided over the medical inquiries have argued that culture change is the
      solution to health care's ills. This is likely to be much harder to institute
      than some people realize, especially given our underlying hunter-gatherer nature.
      This is an evolutionary cleft stick that has not been factored in by those
      optimistic about health sector reform. The implications are that we need a deep
      understanding of human nature in addressing health system problems and to
      recognize that profound culture change is more challenging than many believe.
      Paradoxically, it is when humans are faced with seemingly intractable problems
      that a collective way forward might emerge.

PMID- 15967776
TI  - Epidermal cell patterning and differentiation throughout the apical-basal axis of
      the seedling.
AB  - The idea of common pathways guiding different fates is an emerging concept in
      plant development, and epidermal cell-fate specification in Arabidopsis thaliana
      is an excellent example to illustrate it. In the root epidermis, both hair
      patterning and differentiation depend on a complex interaction between both
      negative (WER, TTG, GL3, EGL3, and GL2) and positive (CPC, TRY, and ETC1)
      regulators of hair cell fate. These regulators pattern and differentiate hairs
      through a bi-directional signalling mechanism. The same molecular components
      (WER, TTG, GL3, EGL3, and GL2) seem to be involved in the patterning of stomata
      in the embryonic stem. However, the possible role of CPC, TRY, and ETC1 on
      stomatal patterning and/or differentiation has not been studied, questioning
      whether they, and the underlying bi-directional mechanism, guide patterning
      formation and differentiation in the hypocotyl.

PMID- 15967777
TI  - Epothilone D affects cell cycle and microtubular pattern in plant cells.
AB  - Epothilones, macrocyclic lactones from culture filtrates of the myxobacterium
      Sorangium cellulosum, are known as taxol-like microtubular drugs in human
      medicine. To date, nothing is known about the effect of epothilones on
      microtubules (MTs) in plant cells and/or on the plant cell cycle. As shown in
      this report, the treatment of tomato cell suspension cultures with epothilone D
      produced a continuous increase in the mitotic index. Dose-response curves
      revealed that epothilone D alters the mitotic index at concentrations as low as
      1.5 microM. Mitotic arrest was already visible after only 2 h of treatment, and
      55% of the cells were arrested after 24 h. As shown by immunocytological methods,
      abnormal spindles are formed during metaphase, which leads to a random
      distribution of chromosomes in the whole cell and prevents the formation of a
      metaphase plate. The process of chromosome decondensation does not seem to be
      affected, because micronuclei form at the same place with the distributed
      chromosomes. This suggests that epothilone D influences the stability of plant
      MTs mainly during metaphase of the mitotic cycle. In metaphase, the effects of
      epothilone D seem to be irreversible, because cells with an abnormal spindle
      could not be recovered after removal of the drug.

PMID- 15967778
TI  - Changes in DNA and microtubules during loss and re-establishment of desiccation
      tolerance in germinating Medicago truncatula seeds.
AB  - Desiccation tolerance (DT) in orthodox seeds is acquired during seed development
      and lost upon imbibition/germination, purportedly upon the resumption of DNA
      synthesis in the radicle cells. In the present study, flow cytometric analyses
      and visualization of microtubules (MTs) in radicle cells of seedlings of Medicago
      truncatula showed that up to a radicle length of 2 mm, there is neither DNA
      synthesis nor cell division, which were first detected in radicles with a length
      of 3 mm. However, DT started to be lost well before the resumption of DNA
      synthesis, when germinating seeds were dried back. By applying an osmotic
      treatment with polyethylene glycol (PEG) before dehydration, it was possible to
      re-establish DT in seedlings with a radicle up to 2 mm long. Dehydration of
      seedlings with a 2 mm radicle, with or without PEG treatment, caused disassembly
      of MTs and appearance of tubulin granules. Subsequent pre-humidification led to
      an almost complete disappearance of both MTs and tubulin granules. Upon
      rehydration, neither MTs nor tubulin granules were detected in radicle cells of
      untreated seedlings, while PEG-treated seedlings were able to reconstitute the
      microtubular cytoskeleton and continue their normal development. Dehydration of
      untreated seedlings also led to an apoptotic-like DNA fragmentation in radicle
      cells, while in PEG-treated seedlings DNA integrity was maintained. The results
      showed that for different cellular components, desiccation-tolerant seedlings may
      apply distinct strategies to survive dehydration, either by avoidance or further
      repair of the damages.

PMID- 15967779
TI  - Identification and characterization of mutants capable of rapid seed germination
      at 10 degrees C from activation-tagged lines of Arabidopsis thaliana.
AB  - Five cold temperature germinating (ctg) mutants, completing germination at 10
      degrees C faster than wild type, have been recovered from activation-tagged
      populations of Arabidopsis thaliana. Three (ctg10-D, 41-D, and 144-D) were tagged
      and segregated 3:1 for BASTA resistance in the F2 when crossed with wild type.
      None of the tagged ctg mutants was disturbed in sensitivity to abscisic acid or
      glucose but all were less sensitive to GA4+7 and osmoticum. The other two mutants
      (ctg156 and ctg225) were recessive, BASTA sensitive, and exhibited a transparent
      testa (tt) phenotype. They were more sensitive to abscisic acid, paclobutrazol,
      and GA4+7 than wild type but had similar sensitivity to osmoticum.
      Dimethylaminocinnamaldehyde staining of seeds from the two tt mutants, compared
      with stained seeds from the publicly available tt lines 1-10, suggested that
      ctg156 was a new allele of tt1, while ctg225 was similar to tt7-1. However,
      reciprocal crosses determined that ctg156 was not allelic to tt1 while ctg225 was
      a new allele of tt7. When the gene was sequenced from ctg225 it was missing 10 bp
      in the second exon, resulting in the incorporation of two spurious amino acids
      (G282E and D283A) followed by a stop. The screen successfully recovered mutants
      completing germination faster than wild type at 10 degrees C.

PMID- 15967780
TI  - Cavitation vulnerability in roots and shoots: does Populus euphratica Oliv., a
      poplar from arid areas of Central Asia, differ from other poplar species?
AB  - Populus euphratica is a poplar species growing in arid regions of Central Asia,
      where its distribution remains nevertheless restricted to river-banks or to areas
      with an access to deep water tables. To test whether the hydraulic architecture
      of this species differs from that of other poplars with respect to this
      ecological distribution, the vulnerability to cavitation of P. euphratica was
      compared with that of P. alba and of P. trichocarpa x koreana. The occurrence of
      a potential hydraulic segmentation through cavitation was also investigated by
      assessing the vulnerability of roots, stems, and leaf mid-rib veins. Cryo
      scanning electron microscopy (cryo-SEM) was used to assess the level of embolism
      in fine roots and leaf mid-ribs and a low pressure flowmeter (LPFM) was used for
      stems and main roots. The cryo-SEM technique was validated against LPFM
      measurements on paired samples. In P. alba and P. trichocarpa x koreana, leaf mid
      ribs were more vulnerable to cavitation than stems and roots. In P. euphratica,
      leaf mid-ribs and stems were equally vulnerable and, contrary to what has been
      observed in other species, roots were significantly less vulnerable than shoots.
      P. euphratica was by far the most vulnerable. The water potential inducing 50%
      loss of conductivity in stems was close to -0.7 MPa, against approximately -1.45
      MPa for the two others species. Such a large vulnerability was confirmed by
      recording losses of conductivity during a gradual drought. Moreover, significant
      stem embolism was recorded before stomatal closure, indicating the lack of an
      efficient safety margin for hydraulic functions in this species. Embolism was not
      reversed by rewatering. These observations are discussed with respect to the
      ecology of P. euphratica.

PMID- 15967781
TI  - GATA-1 is required for expression of Fc{epsilon}RI on mast cells: analysis of
      mast cells derived from GATA-1 knockdown mouse bone marrow.
AB  - The high-affinity receptor for IgE (FcepsilonRI) that is expressed on the surface
      of mast cells plays an important role in antigen/IgE-mediated allergic reactions.
      We have previously found that critical elements in the promoter of the
      FcepsilonRI alpha- and beta-chain genes are recognized by the transcription
      factor GATA-1 in electrophoretic mobility shift assays coupled with a transient
      expression system for the alpha- and beta-chain promoters. To confirm that GATA-1
      is involved in the expression of FcepsilonRI definitively, we generated bone
      marrow-derived mast cells from GATA-1 knockdown (KD) heterozygous mice. FACS
      analysis showed that the frequency of FcepsilonRI-positive cells was
      significantly decreased in mast cells derived from bone marrow of GATA-1 KD mice.
      Reverse transcription-PCR analysis showed that the level of transcripts not only
      for GATA-1 but also for both the alpha- and beta-chains was significantly lower
      in KD mast cells, whereas that of the FcepsilonRI gamma-chain was not affected.
      Degranulation caused by cross-linking of FcepsilonRI on mast cells prepared from
      KD mice was markedly repressed in comparison with that of wild-type mast cells.
      We concluded that the transcription factor GATA-1 positively regulates
      FcepsilonRI alpha- and beta-chain expression and therefore is involved in mast
      cell development.

PMID- 15967782
TI  - Dendritic cell function in mice lacking Plexin C1.
AB  - Semaphorins are secreted or transmembrane proteins that provide essential
      repulsive guidance cues to growing axons or endothelial cells through their
      receptors of the Plexin and Neuropilin family. Semaphorins and Plexins are also
      expressed in the immune system where their function remains elusive. In
      particular, Plexin C1 is expressed by mouse dendritic cells (DCs) and is the
      receptor for the poxvirus semaphorin homolog A39R. We previously found that
      Plexin C1 engagement by A39R inhibits integrin-mediated DC adhesion and chemokine
      induced migration. Here, we show that a cellular ligand for Plexin C1 is
      expressed both by activated T cells and DCs, suggesting that Plexin C1 might be
      engaged on DCs both in cis and in trans. We used Plexin C1(-/-) mice to explore
      the role of Plexin C1 in DC function. DC development is unaffected in these mice.
      In two different in vivo assays, Plexin C1(-/-) DC migration to lymph nodes (LNs)
      was lower than that of wild-type (WT) DC but this difference was not
      statistically significant. Plexin C1(-/-) bone marrow-derived DCs induced normal
      in vitro T cell responses but reduced in vivo T cell responses when injected
      subcutaneously to WT mice. Finally, in vivo T cell responses to ovalbumin peptide
      and contact hypersensitivity to dinitrofluorobenzene were slightly decreased in
      Plexin C1(-/-) mice. These results suggest a role for Plexin C1 in DC migration
      or mobility within the LNs.

PMID- 15967783
TI  - TGF-{beta} signaling of human T cells is modulated by the ancillary TGF-{beta}
      receptor endoglin.
AB  - Transforming growth factor beta (TGF-beta) inhibits T cell activation and alters
      differentiation of naive T cells into effector cells. Although four main cell
      surface proteins can interact with TGF-beta, only the signaling receptors type I
      (TGF-betaR type I) and type II (TGF-betaR type II) have so far been described on
      T cells. The aim of the present study was to investigate the expression of the
      ancillary receptor endoglin (CD105) by T cells and its role in TGF-beta-mediated
      signal transduction and function. CD105 expression was analyzed on resting and
      activated human CD4(+) T cells by flow cytometry, western blot,
      immunoprecipitation, proliferation and SMAD-responsive reporter gene assays.
      CD4(+) T cells constitutively expressed CD105 in memory T cells and partially
      also in naive T cells; however, surface expression is regulated and is increased
      following TCR engagement, which induced serine/threonine phosphorylation of
      CD105. In contrast to the suppressive signal mediated by the TGF-beta, cross
      linking of CD105 substantially enhanced T cell proliferation, indicating that
      CD105 by itself mediates signal transduction. Furthermore, CD105 cross-linking
      induced SMAD-independent signaling via ERK kinase phosphorylation. The present
      study demonstrates that CD105 is expressed on the surface by activated CD4(+) T
      cells and CD3 regulated by post-translational means. Furthermore, CD105 acts as a
      regulatory receptor, counteracting TGF-beta-mediated suppression.

PMID- 15967784
TI  - A minor population of splenic dendritic cells expressing CD19 mediates IDO
      dependent T cell suppression via type I IFN signaling following B7 ligation.
AB  - By ligating CD80/CD86 (B7) molecules, the synthetic immunomodulatory reagent
      CTLA4-Ig (soluble synthetic CTLA4 fusion protein) induces expression of the
      enzyme indoleamine 2,3-dioxygenase (IDO) in some dendritic cells (DCs), which
      acquire potent T cell regulatory functions as a consequence. Here we show that
      this response occurred exclusively in a population of splenic DCs co-expressing
      the marker CD19. B7 ligation induced activation of the transcription factor
      signal transducer and activator of transcription (STAT1) in sorted CD19+, but not
      CD19(NEG), DCs. STAT1 activation occurred even when DCs lacked receptors for type
      II IFN (IFNgamma); however, STAT1 activation and IDO up-regulation were not
      observed when DCs lacked receptors for type I IFN (IFNalphabeta). Thus, IFNalpha,
      but not IFNgamma, signaling was essential for STAT1 activation and IDO up
      regulation in CD19+ DCs following B7 ligation. Consistent with these findings, B7
      ligation also induced sorted CD19+, but not CD19(NEG), DCs to express IFNalpha.
      Moreover, recombinant IFNalpha induced CD19+, but not CD19(NEG), DCs to mediate
      IDO-dependent T cell suppression, showing that IFNalpha signaling could
      substitute for upstream signals from B7. These data reveal that a minor
      population of splenic DCs expressing the CD19 marker is uniquely responsive to B7
      ligation, and that IFNalpha-mediated STAT1 activation is an essential
      intermediary signaling pathway that promotes IDO induction in these DCs. Thus,
      CD19+ DCs may be a target for regulatory T cells expressing surface CTLA4, and
      may suppress T cell responses via induction of IDO.

PMID- 15967785
TI  - BCR targeting of biotin-{alpha}-galactosylceramide leads to enhanced presentation
      on CD1d and requires transport of BCR to CD1d-containing endocytic compartments.
AB  - CD1d is a non-polymorphic MHC class I-related protein that binds and presents
      glycolipid antigens to T cell antigen receptors expressed by NK-like T (NKT)
      cells. CD1d-dependent immune responses play critical roles in infectious disease,
      autoimmunity, allergy and cancer. We tested the hypothesis that B cell antigen
      receptor (BCR) targeting of a biotin-modified version of the CD1d-binding antigen
      alpha-galactosylceramide (biotin-alpha-GalCer) results in enhanced murine CD1d
      mediated presentation as compared with presentation of non-targeted biotin-alpha
      GalCer. Presentation of BCR-targeted antigen to NKT cells was enhanced 100- to
      1000-fold compared with non-targeted antigen. CD1d presentation of BCR-targeted
      antigen was observed after 4 h treatment, consistent with a requirement for
      endosomal trafficking. Furthermore, unlike non-targeted antigen, BCR-targeted
      antigen was not loaded directly onto cell-surface CD1d. Blocking BCR signaling
      with the Syk tyrosine kinase inhibitor piceatannol inhibited presentation of BCR
      targeted antigen but not non-targeted antigen. Piceatannol blocked transport of
      the BCR to CD1d-containing endosomes, showing that intersection of BCR-targeted
      antigen with endosomes is required for enhanced mCD1d antigen presentation. Our
      data suggest that the BCR facilitates capture of low quantities of mCD1d antigens
      to enhance CD1d-dependent immune responses.

PMID- 15967786
TI  - Targeting antigen to CD19 on B cells efficiently activates T cells.
AB  - CD19 is a B cell-surface molecule that participates as an important regulatory
      signaling complex for antigen bound at the surface by Ig. Triggering of CD19
      through its linkage with CD21 amplifies signals transduced through the Src family
      kinases and modulates B cell differentiation in response to antigen. This study
      examines the kinetics of antigen uptake and processing of antigen directly
      targeted to the CD19 protein on purified B cells. We have demonstrated that the
      antigen internalized within minutes through CD19 forms a cap at the B cell
      surface and can be found within lysosomes in the cytoplasm in 90 min. B cells
      acquiring antigen via CD19 express elevated levels of B7-1 and B7-2 co
      stimulatory molecules. Moreover, antigen-anti-CD19 complexes administered
      intravenously bind B cells in vivo and activate antigen-specific T cells more
      efficiently than non-specific uptake and in a manner similar to antigen taken up
      through surface IgM on B cells. This work illustrates an important and previously
      unrecognized mechanism for targeting proteins to B lymphocytes for antigen
      presentation and activation of CD4 T cells.

PMID- 15967787
TI  - Structure and function of lipid rafts in human activated T cells.
AB  - Lipid rafts, specialized membrane microdomains enriched in sphingolipids and
      cholesterol, have been shown to function as signaling platforms in T cells.
      Surface raft expression is known to be increased in human T cells upon
      activation, and this increased raft expression may account for efficient
      signaling capability and decreased dependency for co-stimulation in effector
      and/or activated T cells. However, raft-mediated signaling ability in activated T
      cells remains to be clarified. In this study, we analyzed the structure and
      function of lipid rafts in human activated T cells. We demonstrated that raft
      protein constituents are dramatically changed after activation along with an
      increase in lipid contents. T cells stimulated with anti-CD3 plus anti-CD28
      antibodies showed an increase not only in surface monosialoganglioside GM1
      expression but also in total amounts of raft-associated lipids such as
      sphingomyelin, cholesterol and glycosphingolipids. Raft proteins increased after
      activation include Csk, Csk-binding protein and Fyn, the molecules known to be
      involved in negative regulation of T cell activation. Consistent with the
      increase in expression of these proteins, TCR-mediated Ca(2+) response, a
      response dependent on raft integrity, was clearly inhibited in activated T cells.
      Thus, the structure and function of lipid rafts in human activated T cells seem
      to be quite distinct from those in naive T cells. Further, human activated T
      cells are relatively resistant to signaling, at least transiently, by TCR re
      stimulation even though their raft expression is increased.

PMID- 15967788
TI  - Electrophysiology of the renin-producing juxtaglomerular cells.

PMID- 15967789
TI  - Revised European Best Practice Guidelines for the management of anaemia in
      patients with chronic renal failure, part III.2: treatment of anaemia with iron.

PMID- 15967791
TI  - Effect of inhibition of the bc1 complex on gene expression profile in yeast.
AB  - Because the respiratory chain is the major site of oxidation of the reduced
      equivalents and of energy production in aerobic cells, its inhibition has severe
      impact on the cells. Communication pathways from the respiratory chain are
      required to allow the cell to sense the defect and respond to it. In this work,
      we studied changes in gene expression induced by the treatment of yeast cells
      with myxothiazol, an inhibitor of the bc(1) complex, an enzyme of the respiratory
      chain. The pattern and time-course expression of the genes resemble those of the
      environmental stress response, a common gene expression program induced by sudden
      changes in the environment. In addition, the changes were, for most of the genes,
      mediated through the transcription factors Msn2/4, which play a central role in
      the cellular response to these stresses. By using a mutant with a myxothiazol
      resistant bc(1) complex, we showed that the changes of expression of the majority
      of the genes was caused by the inhibition of the bc(1) complex but that other
      stresses might be involved. The expression pattern of CTT1, coding for a
      cytoplasmic catalase, was further studied. The expression of this gene was
      largely dependent on Msn2/4 and the inhibition of the cytochrome bc(1). Addition
      of oxidants of NADH was found to decrease the expression of CTT1 induced by
      myxothiazol treatment, suggesting that the accumulation of NADH caused by the
      inhibition of the respiratory chain may be involved in the signaling pathway from
      the mitochondria to the transcription factor.

PMID- 15967790
TI  - MAPK-mediated phosphorylation of GATA-1 promotes Bcl-XL expression and cell
      survival.
AB  - In the interleukin 3-dependent hematopoietic cell line Ba/F3, inhibition of
      mitogen-activated protein kinase, a member of the MAPK/c-Jun N-terminal
      kinase/stress-activated protein kinase kinase family that plays an important role
      in cell growth and death control, rapidly leads to severe apoptosis. However,
      most of the antiapoptotic substrates of MAPK remain to be identified. Here we
      report that, upon interleukin-3 stimulation of Ba/F3 cells, the transcription
      factor GATA-1 is strongly phosphorylated at residue serine 26 by a MAPK-dependent
      pathway. Phosphorylation of GATA-1 increases GATA-1-mediated transcription of the
      E4bp4 survival gene without significantly changing the DNA-binding affinity of
      GATA-1. Further characterization of GATA-1 phosphorylation site mutants revealed
      that the antiapoptotic function of GATA-1 is strongly dependent upon its
      phosphorylation at the Ser-26 position and is probably mediated through its up
      regulation of Bcl-X(L) expression. Taken together, our data demonstrate that MAPK
      dependent GATA-1 phosphorylation is important for its transactivation of the
      E4bp4 gene, Bcl-X(L) expression and cell survival. Therefore, GATA-1 may
      represent a novel MAPK substrate that plays an essential role in a cytokine
      mediated antiapoptotic response.

PMID- 15967792
TI  - Regulation and surveillance of normal and 3'-extended forms of the yeast aci
      reductone dioxygenase mRNA by RNase III cleavage and exonucleolytic degradation.
AB  - Aci-reductone dioxygenases are key enzymes in the methionine salvage pathway. The
      mechanisms by which the expression of this important class of enzymes is
      regulated are poorly understood. Here we show that the expression of the mRNA
      encoding the yeast aci-reductone dioxygenase ADI1 is controlled post
      transcriptionally by RNase III cleavage. Cleavage occurs in a large bipartite
      stem loop structure present in the open reading frame region of the ADI1 mRNA.
      The ADI1 mRNA is up-regulated in the absence of the yeast orthologue of RNase III
      Rnt1p or of the 5' --> 3' exonucleases Xrn1p and Rat1p. 3'-Extended forms of this
      mRNA, including a polycistronic mRNA ADI1-YMR010W mRNA, also accumulate in cells
      lacking Rnt1p, Xrn1p, and Rat1p or the nuclear exosome component Rrp6p,
      suggesting that these 3'-extended forms are subject to nuclear surveillance. We
      show that the ADI1 mRNA is up-regulated under heat shock conditions in a Rnt1p
      independent manner. We propose that Rnt1p cleavage targets degradation of the
      ADI1 mRNA to prevent its expression prior to heat shock conditions and that RNA
      surveillance by multiple ribonucleases helps prevent accumulation of aberrant 3'
      extended forms of this mRNA that arise from intrinsically inefficient 3'
      processing signals.

PMID- 15967793
TI  - The zebrafish retinol dehydrogenase, rdh1l, is essential for intestinal
      development and is regulated by the tumor suppressor adenomatous polyposis coli.
AB  - Retinoic acid (RA) is a potent signaling molecule that plays important roles in
      multiple and diverse developmental processes. The contribution of retinoic acid
      to promoting the development and differentiation of the vertebrate intestine and
      the factors that regulate RA production in the gut remain poorly defined. Herein,
      we report that the novel retinol dehydrogenase, rdh1l, is required for proper gut
      development and differentiation. rdh1l is expressed ubiquitously during early
      development but becomes restricted to the gut by 3 days postfertilization.
      Knockdown of rdh1l results in a robust RA-deficient phenotype including lack of
      intestinal differentiation, which can be rescued by the addition of exogenous
      retinoic acid. We report that adenomatous polyposis coli (APC) mutant zebrafish
      harbor an RA-deficient phenotype including aberrant intestinal differentiation
      and that these mutants can be rescued by treatment with retinoic acid or
      injection of rdh1l mRNA. Further, we have found that although APC mutants are
      deficient in rdh1l expression, they harbor increased expression of raldh2
      suggesting the control of RA production by APC is via retinol dehydrogenase
      activity. These results provide genetic evidence that retinoic acid is required
      for vertebrate gut development and that the tumor suppressor APC controls the
      production of RA in the gut by regulating the expression of the retinol
      dehydrogenase, rdh1l.

PMID- 15967794
TI  - A ligand-mediated hydrogen bond network required for the activation of the
      mineralocorticoid receptor.
AB  - Ligand binding is the first step in hormone regulation of mineralocorticoid
      receptor (MR) activity. Here, we report multiple crystal structures of MR (NR3C2)
      bound to both agonist and antagonists. These structures combined with mutagenesis
      studies reveal that maximal receptor activation involves an intricate ligand
      mediated hydrogen bond network with Asn770 which serves dual roles: stabilization
      of the loop preceding the C-terminal activation function-2 helix and direct
      contact with the hormone ligand. In addition, most activating ligands hydrogen
      bond to Thr945 on helix 10. Structural characterization of the naturally
      occurring S810L mutant explains how stabilization of a helix 3/helix 5
      interaction can circumvent the requirement for this hydrogen bond network. Taken
      together, these results explain the potency of MR activation by aldosterone, the
      weak activation induced by progesterone and the antihypertensive agent
      spironolactone, and the binding selectivity of cortisol over cortisone.

PMID- 15967795
TI  - Methionine sulfoxide and proteolytic cleavage contribute to the inactivation of
      cathepsin G by hypochlorous acid: an oxidative mechanism for regulation of serine
      proteinases by myeloperoxidase.
AB  - Using myeloperoxidase and hydrogen peroxide, activated neutrophils produce high
      local concentrations of hypochlorous acid (HOCl). They also secrete cathepsin G,
      a serine protease implicated in cytokine release, receptor activation, and
      degradation of tissue proteins. Isolated cathepsin G was inactivated by HOCl but
      not by hydrogen peroxide in vitro. We found that activated neutrophils lost
      cathepsin G activity by a pathway requiring myeloperoxidase, suggesting that
      oxidants generated by myeloperoxidase might regulate cathepsin G activity in
      vivo. Tandem mass spectrometric analysis of oxidized cathepsin G revealed that
      loss of a peptide containing Asp108, which lies in the active site, associated
      quantitatively with loss of enzymatic activity. Catalytic domain peptides
      containing Asp108 were lost from the oxidized protein in concert with the
      conversion of Met110 to the sulfoxide. Release of this peptide was blocked by
      pretreating cathepsin G with phenylmethylsulfonyl fluoride, strongly implying
      that oxidation introduced proteolytic cleavage sites into cathepsin G. Model
      system studies demonstrated that methionine oxidation can direct the
      regiospecific proteolysis of peptides by cathepsin G. Thus, oxidation of Met110
      may contribute to cathepsin G inactivation by at least two distinct mechanisms.
      One involves direct oxidation of the thioether residue adjacent to the aspartic
      acid in the catalytic domain. The other involves the generation of new sites that
      are susceptible to proteolysis by cathepsin G. These observations raise the
      possibility that oxidants derived from neutrophils restrain pericellular
      proteolysis by inactivating cathepsin G. They also suggest that methionine
      oxidation could render cathepsin G susceptible to autolytic cleavage.
      Myeloperoxidase may thus play a previously unsuspected role in regulating tissue
      injury by serine proteases during inflammation.

PMID- 15967796
TI  - Protein phosphatase 5 is a negative modulator of heat shock factor 1.
AB  - The major stress protein transcription factor, heat shock factor (HSF1), is
      tightly regulated through a multilayered activation-deactivation process
      involving oligomerization, post-translational modification, and interaction with
      the heat shock protein (Hsp90)-containing multichaperone complex. Conditions of
      proteotoxic stress, such as heat shock, trigger reversible assembly of latent
      HSF1 monomers into DNA-binding homotrimers that bind with high affinity to
      cognate heat shock elements. Transactivation is a second and independently
      regulated function of HSF1 that is accompanied by hyperphosphorylation and
      appears to involve a number of signaling events. Association of HSF1 with Hsp90
      chaperone complexes provides additional regulatory complexity, however, not all
      the co-chaperones have been identified, and the specific molecular interactions
      throughout the activation/deactivation pathway remain to be determined. Here we
      demonstrate that protein phosphatase 5 (PP5), a tetratricopeptide domain
      containing component of Hsp90-steroid receptor complexes, functions as a negative
      modulator of HSF1 activity. Physical interactions between PP5 and HSF1-Hsp90
      complexes were observed in co-immunoprecipitation and gel mobility supershift
      experiments. Overexpression of PP5 or activation of endogenous phosphatase
      activity resulted in diminished HSF1 DNA binding and transcriptional activities,
      and accelerated recovery. Conversely, microinjection of PP5 antibodies, or
      inhibition of its phosphatase activity in vivo, significantly delayed trimer
      disassembly after heat shock. Inhibition of PP5 activity did not activate HSF1 in
      unstressed cells. These results indicate that PP5 is a negative modulator of HSF1
      activity.

PMID- 15967797
TI  - Increased levels of inositol hexakisphosphate (InsP6) protect HEK293 cells from
      tumor necrosis factor (alpha)- and Fas-induced apoptosis.
AB  - The overexpression of inositol 1,3,4-trisphosphate 5/6-kinase has recently been
      shown to protect HEK293 cells from tumor necrosis factor alpha (TNF(alpha))
      induced apoptosis. This overexpression leads to an increase in the levels of both
      inositol 1,3,4,5,6-pentakisphosphate (InsP5) and inositol 1,2,3,4,5,6
      hexakisphosphate (InsP6). Cells that overexpress InsP5 2-kinase have increased
      levels of InsP6 and are also protected from TNFalpha-induced apoptosis;
      furthermore, cells that express an RNA interference construct to the 2-kinase are
      deficient in InsP6 and are sensitized to TNFalpha-induced apoptosis. Therefore
      the protective effect of 5/6-kinase on TNFalpha-mediated apoptosis is due to an
      increase of InsP6 or to a metabolite derived from InsP6. Furthermore, we find
      that the InsP6 also protects from Fas-mediated apoptosis. No effect was seen in
      the endocytic rate of transferrin receptor, caspase 8 activity, or TNF receptor
      number at the cell surface. Cells that overexpress 2-kinase do show an increase
      in the amount of receptor-interacting protein (RIP), while cells with reduced
      InsP6 levels show relatively less RIP, providing a possible mechanism for the
      effect on apoptosis.

PMID- 15967798
TI  - The acute box cis-element in human heavy ferritin mRNA 5'-untranslated region is
      a unique translation enhancer that binds poly(C)-binding proteins.
AB  - Intracellular levels of the light (L) and heavy (H) ferritin subunits are
      regulated by iron at the level of message translation via a modulated interaction
      between the iron regulatory proteins (IRP1 and IRP2) and a 5'-untranslated
      region. Iron-responsive element (IRE). Here we show that iron and interleukin
      1beta (IL-1beta) act synergistically to increase H- and L-ferritin expression in
      hepatoma cells. A GC-rich cis-element, the acute box (AB), located downstream of
      the IRE in the H-ferritin mRNA 5'-untranslated region, conferred a substantial
      increase in basal and IL-1beta-stimulated translation over a similar time course
      to the induction of endogenous ferritin. A scrambled version of the AB was
      unresponsive to IL-1. Targeted mutation of the AB altered translation; reverse
      orientation and a deletion of the AB abolished the wild-type stem-loop structure
      and abrogated translational enhancement, whereas a conservative structural mutant
      had little effect. Labeled AB transcripts formed specific complexes with hepatoma
      cell extracts that contained the poly(C)-binding proteins, iso-alphaCP1 and 
      alphaCP2, which have well defined roles as translation regulators. Iron influx
      increased the association of alphaCP1 with ferritin mRNA and decreased the
      alphaCP2-ferritin mRNA interaction, whereas IL-1beta reduced the association of
      alphaCP1 and alphaCP2 with H-ferritin mRNA. In summary, the H-ferritin mRNA AB is
      a key cis-acting translation enhancer that augments H-subunit expression in Hep3B
      and HepG2 hepatoma cells, in concert with the IRE. The regulated association of H
      ferritin mRNA with the poly(C)-binding proteins suggests a novel role for these
      proteins in ferritin translation and iron homeostasis in human liver.

PMID- 15967799
TI  - N-methyl-D-aspartate receptor subtype mediated bidirectional control of p38
      mitogen-activated protein kinase.
AB  - N-methyl-d-aspartate receptor (NMDAR) stimulation activates many downstream
      mechanisms involved in both cell survival and cell death. The manner in which the
      NMDAR regulates one of these pathways, the p38 mitogen-activated protein kinase
      (p38) pathway, is currently unknown. In the present study, we have defined a
      developmental-, concentration-, and time-dependent phosphorylation and subsequent
      dephosphorylation of p38. In cultured hippocampal neurons 7-8 days in vitro (DIV7
      8), NMDAR stimulation leads to a concentration-dependent increase in p38
      phosphorylation (phospho-p38). However, in more mature neurons (>DIV17)
      application of NMDA produces concentration-dependent effects, such that low
      concentrations result in sustained increases in phospho-p38 levels, and high
      concentrations dephosphorylate p38 within 5 min. Conantokin G, an antagonist of
      NR1/2A/2B and NR1/2B receptors, inhibits p38 phosphorylation, while NR1/2B
      specific antagonists prevent the rapid dephosphorylation of p38 without affecting
      p38 activation. Furthermore, inhibition of calcineurin prevents the activation of
      p38, whereas inhibition of phosphoinositide 3-kinase (PI3K) prevents the rapid
      dephosphorylation of p38. Our results support the presence of subtype-dependent
      pathways regulating p38 activation and deactivation: one involves NR1/2A/2B
      receptors activating calcineurin and resulting in p38 phosphorylation, and the
      other utilizes NR1/2B receptors binding to and activating PI3K and leading to the
      dephosphorylation of p38 in a manner involving both NR1/2A/2B receptor activation
      and tyrosine phosphorylation of NR2B. The ability of NMDAR subtype-specific
      mechanisms to regulate p38 has implications for NMDAR-mediated synaptic
      plasticity, gene regulation, and excitotoxicity.

PMID- 15967800
TI  - Radical S-adenosylmethionine enzyme coproporphyrinogen III oxidase HemN:
      functional features of the [4Fe-4S] cluster and the two bound S-adenosyl-L
      methionines.
AB  - The S-adenosylmethionine (AdoMet) radical enzyme oxygen-independent
      coproporphyrinogen III oxidase HemN catalyzes the oxidative decarboxylation of
      coproporphyrinogen III to protoporphyrinogen IX during bacterial heme
      biosynthesis. The recently solved crystal structure of Escherichia coli HemN
      revealed the presence of an unusually coordinated iron-sulfur cluster and two
      molecules of AdoMet. EPR spectroscopy of the reduced iron-sulfur center in
      anaerobically purified HemN in the absence of AdoMet has revealed a [4Fe-4S](1+)
      cluster in two slightly different conformations. Mossbauer spectroscopy of
      anaerobically purified HemN has identified a predominantly [4Fe-4S](2+) cluster
      in which only three iron atoms were coordinated by cysteine residues (isomer
      shift of delta = 0.43 (1) mm/s). The fourth non-cysteine-ligated iron exhibited a
      delta = 0.57 (3) mm/s, which shifted to a delta = 0.68 (3) mm/s upon addition of
      AdoMet. Substrate binding by HemN did not alter AdoMet coordination to the
      cluster. Multiple rounds of AdoMet cleavage with the formation of the reaction
      product methionine indicated AdoMet consumption during catalysis and identified
      AdoMet as a co-substrate for HemN catalysis. AdoMet cleavage was found to be
      dependent on the presence of the substrate coproporphyrinogen III. Two molecules
      of AdoMet were cleaved during one catalytic cycle for the formation of one
      molecule of protoporphyrinogen IX. Finally, the binding site for the unusual
      second, non iron-sulfur cluster coordinating AdoMet molecule (AdoMet2) was
      targeted using site-directed mutagenesis. All AdoMet2 binding site mutants still
      contained an iron-sulfur cluster and most still exhibited AdoMet cleavage, albeit
      reduced compared with the wild-type enzyme. However, all mutants lost their
      overall catalytic ability indicating a functional role for AdoMet2 in HemN
      catalysis. The reported significant correlation of structural and functional
      biophysical and biochemical data identifies HemN as a useful model system for the
      elucidation of general AdoMet radical enzyme features.

PMID- 15967801
TI  - Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor
      binding sites specifically increase binding affinity for GnRH II but not GnRH I:
      evidence for ligand-selective, receptor-active conformations.
AB  - The human gonadotropin-releasing hormone (GnRH) receptor is evolutionarily
      configured for high affinity binding of GnRH I ([Tyr(5),Leu(7),Arg(8)]GnRH) but
      at lower affinity for GnRH II ([His(5),Trp(7),Tyr(8)]GnRH). GnRH I is more potent
      in the activation of the G(q/11) protein in the gonadotrope; however, GnRH II is
      more potent in the stimulation of apoptosis and antiproliferative effects through
      activating G(i) protein-mediated signaling, implying that GnRH I and II
      selectively stabilize different receptor-active conformations that preferentially
      couple to different signaling pathways. Receptor activation involves ligand
      induction or conformational selection, but the molecular basis of the
      communication between ligand-binding sites and receptor allosteric sites remains
      unclear. We have sought conformational coupling between receptor-ligand
      intermolecular interactions and intramolecular interaction networks in the human
      GnRH receptor by mutating remote residues that induce differential ligand binding
      affinity shifts for GnRH I and II. We have demonstrated that certain Ala
      mutations in the intracellular segments of transmembrane domains 3 (Met(132)), 5
      (Met(227)), 6 (Phe(272) and Phe(276)), and 7 (Ile(322) and Tyr(323)) of the human
      GnRH receptor allosterically increased ligand binding affinity for GnRH II but
      had little effect on GnRH I binding affinity. We examined the role of the three
      amino acids that differ in these two ligands, and we found that Tyr(8) in GnRH II
      plays a dominant role for the increased affinity of the receptor mutants for GnRH
      II. We propose that creation of a high affinity binding site for GnRH II
      accompanies receptor conformational changes, i.e."induced fit" or "conformational
      selection," mainly determined by the intermolecular interactions between Tyr(8)
      and the receptor contact residues, which can be facilitated by disruption of
      particular sets of receptor-stabilizing intramolecular interactions. The findings
      suggest that GnRH I and II binding may selectively stabilize different receptor
      active conformations and therefore different ligand-induced selective signaling
      described previously for these ligands.

PMID- 15967802
TI  - Functional significance of type 1 insulin-like growth factor-mediated nuclear
      translocation of the insulin receptor substrate-1 and beta-catenin.
AB  - Previous work has shown that the transcriptional regulator beta-catenin can
      translocate to the nuclei when cells are stimulated with the type 1 insulin-like
      growth factor (IGF-1). We show by immunocoprecipitation and by confocal
      microscopy that beta-catenin binds to and co-localizes with the insulin receptor
      substrate-1 (IRS-1), a docking protein for both the insulin and the IGF-1
      receptors. IRS-1 is required for IGF-1-mediated nuclear translocation of beta
      catenin, resulting in the activation of the beta-catenin target genes. IGF-1
      mediated nuclear translocation of beta-catenin is facilitated by the nuclear
      translocation of IRS-1. Both IRS-1 and beta-catenin are recruited to the cyclin
      D1 promoter, an established target for beta-catenin, but only IRS-1 is recruited
      to the ribosomal DNA (rDNA) promoter. UBF proteins (known to interact with both
      IRS-1 and beta-catenin) are also detectable in the cyclin D1 and rDNA promoters.
      These results indicate that IRS-1 (activated by the IGF-1 receptor) is one of
      several proteins that regulate the subcellular localization and activity of beta
      catenin. The ability of IRS-1 to localize to both RNA polymerase II (with beta
      catenin) and RNA polymerase I-regulated promoters suggest an explanation for the
      effect of IRS-1 on both cell growth in size and cell proliferation. This
      possibility is supported by the demonstration that enforced nuclear localization
      of IRS-1 causes nuclear translocation of beta-catenin and transformation of
      normal mouse embryo fibroblasts (colony formation in soft agar).

PMID- 15967803
TI  - Cloning of the rat pyruvate dehydrogenase kinase 4 gene promoter: activation of
      pyruvate dehydrogenase kinase 4 by the peroxisome proliferator-activated receptor
      gamma coactivator.
AB  - The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate to acetyl
      CoA in mitochondria and is a key regulatory enzyme in the metabolism of glucose
      to acetyl-CoA. Phosphorylation of pyruvate dehydrogenase by the pyruvate
      dehydrogenase kinases (PDK) inhibits pyruvate dehydrogenase complex activity.
      There are four PDK isoforms, and expression of PDK4 and PDK2 genes is elevated in
      starvation and diabetes, allowing glucose to be conserved while fatty acid
      oxidation is increased. In these studies we have investigated the transcriptional
      mechanisms by which the expression of the PDK4 gene is increased. The peroxisome
      proliferator-activated receptor gamma coactivator (PGC-1alpha) stimulates the
      expression of genes involved in hepatic gluconeogenesis and mitochondrial fatty
      acid oxidation. We have found that PGC-1alpha will induce the expression of both
      the PDK2 and PDK4 genes in primary rat hepatocytes and ventricular myocytes. We
      cloned the promoter for the rat PDK4 gene. Hepatic nuclear factor 4 (HNF4), which
      activates many genes in the liver, will induce PDK4 expression. Although HNF4 and
      PGC-1alpha interact to stimulate several genes encoding gluconeogenic enzymes,
      the induction of PDK4 does not involve interactions of PGC-1alpha with HNF4.
      Using the chromatin immunoprecipitation assay, we have demonstrated that HNF4 and
      PGC-1alpha are associated with the PDK4 gene in vivo. Our data suggest that by
      inducing PDK genes PGC-1alpha will direct pyruvate away from metabolism into
      acetyl-CoA and toward the formation of oxaloacetate and into the gluconeogenic
      pathway.

PMID- 15967804
TI  - Expression of the chemokine receptors CXCR4, CXCR5, and CCR7 in primary central
      nervous system lymphoma.

PMID- 15967805
TI  - Detection of single DNA molecules by multicolor quantum-dot end-labeling.
AB  - Observation of DNA-protein interactions by single molecule fluorescence
      microscopy is usually performed by using fluorescent DNA binding agents. However,
      such dyes have been shown to induce cleavage of the DNA molecule and perturb its
      interactions with proteins. A new method for the detection of surface-attached
      DNA molecules by fluorescence microscopy is introduced in this paper. Biotin-
      and/or digoxigenin-modified DNA fragments are covalently linked at both
      extremities of a DNA molecule via sequence-specific hybridization and ligation.
      After the modified DNA molecules have been stretched on a glass surface, their
      ends are visualized by multicolor fluorescence microscopy using conjugated
      quantum dots (QD). We demonstrate that under carefully selected conditions, the
      position and orientation of individual DNA molecules can be inferred with good
      efficiency from the QD fluorescence signals alone. This is achieved by selecting
      QD pairs that have the distance and direction expected for the combed DNA
      molecules. Direct observation of single DNA molecules in the absence of DNA
      staining agent opens new possibilities in the fundamental study of DNA-protein
      interactions. This work also documents new possibilities regarding the use of QD
      for nucleic acid detection and analysis.

PMID- 15967806
TI  - High-throughput alternative splicing quantification by primer extension and
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Alternative splicing is a significant contributor to transcriptome diversity, and
      a high-throughput experimental method to quantitatively assess predictions from
      expressed sequence tag and microarray analyses may help to answer questions about
      the extent and functional significance of these variants. Here, we describe a
      method for high-throughput analysis of known or suspected alternative splicing
      variants (ASVs) using PCR, primer extension and matrix-assisted laser desorption
      ionization time-of-flight mass spectrometry (MALDI-TOF MS). Reverse-transcribed
      mRNA is PCR amplified with primers surrounding the site of alternative splicing,
      followed by a primer extension reaction designed to target sequence disparities
      between two or more variants. These primer extension products are assayed on a
      MALDI-TOF mass spectrometer and analyzed automatically. This method is high
      throughput, highly accurate and reproducible, allowing for the verification of
      the existence of splicing variants in a variety of samples. An example given also
      demonstrates how this method can eliminate potential pitfalls from ordinary gel
      electrophoretic analysis of splicing variants where heteroduplexes formed from
      different variants can produce erroneous results. The new method can be used to
      create alternative variant profiles for cancer markers, to study complex splicing
      regulation, or to screen potential splicing therapies.

PMID- 15967807
TI  - Identification of regulatory targets of tissue-specific transcription factors:
      application to retina-specific gene regulation.
AB  - Identification of tissue-specific gene regulatory networks can yield insights
      into the molecular basis of a tissue's development, function and pathology. Here,
      we present a computational approach designed to identify potential regulatory
      target genes of photoreceptor cell-specific transcription factors (TFs). The
      approach is based on the hypothesis that genes related to the retina in terms of
      expression, disease and/or function are more likely to be the targets of retina
      specific TFs than other genes. A list of genes that are preferentially expressed
      in retina was obtained by integrating expressed sequence tag, SAGE and microarray
      datasets. The regulatory targets of retina-specific TFs are enriched in this set
      of retina-related genes. A Bayesian approach was employed to integrate
      information about binding site location relative to a gene's transcription start
      site. Our method was applied to three retina-specific TFs, CRX, NRL and NR2E3,
      and a number of potential targets were predicted. To experimentally assess the
      validity of the bioinformatic predictions, mobility shift, transient transfection
      and chromatin immunoprecipitation assays were performed with five predicted CRX
      targets, and the results were suggestive of CRX regulation in 5/5, 3/5 and 4/5
      cases, respectively. Together, these experiments strongly suggest that RP1,
      GUCY2D, ABCA4 are novel targets of CRX.

PMID- 15967808
TI  - A deoxyribozyme that synthesizes 2',5'-branched RNA with any branch-site
      nucleotide.
AB  - RNA molecules with internal 2',5'-branches are intermediates in RNA splicing, and
      branched RNAs have recently been proposed as retrotransposition intermediates. A
      broadly applicable in vitro synthetic route to branched RNA that does not require
      self-splicing introns or spliceosomes would substantially improve our ability to
      study biochemical processes that involve branched RNA. We recently described
      7S11, a deoxyribozyme that was identified by in vitro selection and has general
      RNA branch-forming ability. However, an important restriction for 7S11 is that
      the branch-site RNA nucleotide must be a purine (A or G), because a pyrimidine (U
      or C) is not tolerated. Here, we describe the compact 6CE8 deoxyribozyme
      (selected using a 20 nt random region) that synthesizes 2',5'-branched RNA with
      any nucleotide at the branch site. The Mn2+-dependent branch-forming ligation
      reaction is between an internal branch-site 2'-hydroxyl nucleophile on one RNA
      substrate with a 5'-triphosphate on another RNA substrate. The preference for the
      branch-site nucleotide is U > C congruent with A > G, although all four
      nucleotides are tolerated with useful ligation rates. Nearly all other
      nucleotides elsewhere in both RNA substrates allow ligation activity, except that
      the sequence requirement for the RNA strand with the 5'-triphosphate is 5'-pppGA,
      with 5'-pppGAR (R = purine) preferred. These characteristics permit 6CE8 to
      prepare branched RNAs of immediate practical interest, such as the proposed
      branched intermediate of Ty1 retrotransposition. Because this branched RNA has
      two strands with identical sequence that emerge from the branch site, we
      developed strategies to control which of the two strands bind with the
      deoxyribozyme during the branch-forming reaction. The ability to synthesize the
      proposed branched RNA of Ty1 retrotransposition will allow us to explore this
      important biochemical pathway in greater detail.

PMID- 15967809
TI  - Epigenetic manipulation of gene expression: a toolkit for cell biologists.
AB  - Cell biologists have been afforded extraordinary new opportunities for
      experimentation by the emergence of powerful technologies that allow the
      selective manipulation of gene expression. Currently, RNA interference is very
      much in the limelight; however, significant progress has also been made with two
      other approaches. Thus, antisense oligonucleotide technology is undergoing a
      resurgence as a result of improvements in the chemistry of these molecules,
      whereas designed transcription factors offer a powerful and increasingly
      convenient strategy for either up- or down-regulation of targeted genes. This
      mini-review will highlight some of the key features of these three approaches to
      gene regulation, as well as provide pragmatic guidance concerning their use in
      cell biological experimentation based on our direct experience with each of these
      technologies. The approaches discussed here are being intensely pursued in terms
      of possible therapeutic applications. However, we will restrict our comments
      primarily to the cell culture situation, only briefly alluding to fundamental
      differences between utilization in animals versus cells.

PMID- 15967810
TI  - Histone H1 is essential for mitotic chromosome architecture and segregation in
      Xenopus laevis egg extracts.
AB  - During cell division, condensation and resolution of chromosome arms and the
      assembly of a functional kinetochore at the centromere of each sister chromatid
      are essential steps for accurate segregation of the genome by the mitotic
      spindle, yet the contribution of individual chromatin proteins to these processes
      is poorly understood. We have investigated the role of embryonic linker histone
      H1 during mitosis in Xenopus laevis egg extracts. Immunodepletion of histone H1
      caused the assembly of aberrant elongated chromosomes that extended off the
      metaphase plate and outside the perimeter of the spindle. Although functional
      kinetochores assembled, aligned, and exhibited poleward movement, long and
      tangled chromosome arms could not be segregated in anaphase. Histone H1 depletion
      did not significantly affect the recruitment of known structural or functional
      chromosomal components such as condensins or chromokinesins, suggesting that the
      loss of H1 affects chromosome architecture directly. Thus, our results indicate
      that linker histone H1 plays an important role in the structure and function of
      vertebrate chromosomes in mitosis.

PMID- 15967811
TI  - Stress granules and processing bodies are dynamically linked sites of mRNP
      remodeling.
AB  - Stress granules (SGs) are cytoplasmic aggregates of stalled translational
      preinitiation complexes that accumulate during stress. GW bodies/processing
      bodies (PBs) are distinct cytoplasmic sites of mRNA degradation. In this study,
      we show that SGs and PBs are spatially, compositionally, and functionally linked.
      SGs and PBs are induced by stress, but SG assembly requires eIF2alpha
      phosphorylation, whereas PB assembly does not. They are also dispersed by
      inhibitors of translational elongation and share several protein components,
      including Fas-activated serine/threonine phosphoprotein, XRN1, eIF4E, and
      tristetraprolin (TTP). In contrast, eIF3, G3BP, eIF4G, and PABP-1 are restricted
      to SGs, whereas DCP1a and 2 are confined to PBs. SGs and PBs also can harbor the
      same species of mRNA and physically associate with one another in vivo, an
      interaction that is promoted by the related mRNA decay factors TTP and BRF1. We
      propose that mRNA released from disassembled polysomes is sorted and remodeled at
      SGs, from which selected transcripts are delivered to PBs for degradation.

PMID- 15967812
TI  - Septin-dependent compartmentalization of the endoplasmic reticulum during yeast
      polarized growth.
AB  - Polarized cells frequently use diffusion barriers to separate plasma membrane
      domains. It is unknown whether diffusion barriers also compartmentalize
      intracellular organelles. We used photobleaching techniques to characterize
      protein diffusion in the yeast endoplasmic reticulum (ER). Although a soluble
      protein diffused rapidly throughout the ER lumen, diffusion of ER membrane
      proteins was restricted at the bud neck. Ultrastructural studies and fluorescence
      microscopy revealed the presence of a ring of smooth ER at the bud neck. This ER
      domain and the restriction of diffusion for ER membrane proteins through the bud
      neck depended on septin function. The membrane-associated protein Bud6 localized
      to the bud neck in a septin-dependent manner and was required to restrict the
      diffusion of ER membrane proteins. Our results indicate that Bud6 acts downstream
      of septins to assemble a fence in the ER membrane at the bud neck. Thus, in
      polarized yeast cells, diffusion barriers compartmentalize the ER and the plasma
      membrane along parallel lines.

PMID- 15967813
TI  - Musculin/MyoR is expressed in kidney side population cells and can regulate their
      function.
AB  - Musculin/MyoR is a new member of basic helix-loop-helix transcription factors,
      and its expression is limited to skeletal muscle precursors. Here, we report that
      musculin/MyoR is expressed in adult kidney side population (SP) cells and can
      regulate their function. SP phenotype can be used to purify stem cell-rich
      fractions. Microarray analysis clarified that musculin/MyoR was exclusively
      expressed in kidney SP cells, and the cells resided in the renal interstitial
      space. Musculin/MyoR-positive cells were decreased in acute renal failure, but
      infusion of kidney SP cells increased musculin/MyoR-positive cells and improved
      renal function. Kidney SP cells in reversible acute renal failure expressed a
      high level of renoprotective factors and leukemia inhibitory factor (LIF), but
      not in irreversible chronic renal failure. In cultured kidney SP cells, LIF
      stimulated gene expression of renoprotective factors, and down-regulation of
      musculin/MyoR augmented LIF-induced gene expression. Our results suggest that
      musculin/MyoR may play important roles not only in developmental processes but
      also in regenerative processes in adult tissue.

PMID- 15967814
TI  - Conditional knockout of focal adhesion kinase in endothelial cells reveals its
      role in angiogenesis and vascular development in late embryogenesis.
AB  - Focal adhesion kinase (FAK) is a critical mediator of signal transduction by
      integrins and growth factor receptors in a variety of cells including endothelial
      cells (ECs). Here, we describe EC-specific knockout of FAK using a Cre-loxP
      approach. In contrast to the total FAK knockout, deletion of FAK specifically in
      ECs did not affect early embryonic development including normal vasculogenesis.
      However, in late embryogenesis, FAK deletion in the ECs led to defective
      angiogenesis in the embryos, yolk sac, and placenta, impaired vasculature and
      associated hemorrhage, edema, and developmental delay, and late embryonic lethal
      phenotype. Histologically, ECs and blood vessels in the mutant embryos present a
      disorganized, detached, and apoptotic appearance. Consistent with these
      phenotypes, deletion of FAK in ECs isolated from the floxed FAK mice led to
      reduced tubulogenesis, cell survival, proliferation, and migration in vitro.
      Together, these results strongly suggest a role of FAK in angiogenesis and
      vascular development due to its essential function in the regulation of multiple
      EC activities.

PMID- 15967815
TI  - Quantitative electron microscopy and fluorescence spectroscopy of the membrane
      distribution of influenza hemagglutinin.
AB  - Although lipid-dependent protein clustering in biomembranes mediates numerous
      functions, there is little consensus among membrane models on cluster
      organization or size. Here, we use influenza viral envelope protein hemagglutinin
      (HA(0)) to test the hypothesis that clustering results from proteins partitioning
      into preexisting, fluid-ordered "raft" domains, wherein they have a random
      distribution. Japan HA(0) expressed in fibroblasts was visualized by electron
      microscopy using immunogold labeling and probed by fluorescence resonance energy
      transfer (FRET). Labeled HA coincided with electron-dense, often noncircular
      membrane patches. Poisson and K-test (Ripley, B.D. 1977. J. R. Stat. Soc. Ser. B.
      39:172-212) analyses reveal clustering on accessible length scales (20-900 nm).
      Membrane treatments with methyl-beta-cyclodextrin and glycosphingolipid synthesis
      inhibitors did not abolish clusters but did alter their pattern, especially at
      the shortest lengths, as was corroborated by changes in FRET efficiency. The
      magnitude and density dependence of the measured FRET efficiency also indicated a
      nonrandom distribution on molecular length scales (approximately 6-7 nm). This
      work rules out the tested hypothesis for HA over the accessible length scales,
      yet shows clearly how the spatial distribution of HA depends on lipid
      composition.

PMID- 15967816
TI  - Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway
      of extracellular matrix turnover during malignancy.
AB  - We recently reported that uPARAP/Endo180 can mediate the cellular uptake and
      lysosomal degradation of collagen by cultured fibroblasts. Here, we show that
      uPARAP/Endo180 has a key role in the degradation of collagen during mammary
      carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is
      widely expressed in periductal fibroblast-like mesenchymal cells that line
      mammary epithelial cells. This pattern of uPARAP/Endo180 expression is preserved
      during polyomavirus middle T-induced mammary carcinogenesis, with strong
      uPARAP/Endo180 expression by mesenchymal cells embedded within the collagenous
      stroma surrounding nests of uPARAP/Endo180-negative tumor cells. Genetic ablation
      of uPARAP/Endo180 impaired collagen turnover that is critical to tumor expansion,
      as evidenced by the abrogation of cellular collagen uptake, tumor fibrosis, and
      blunted tumor growth. These studies identify uPARAP/Endo180 as a key mediator of
      collagen turnover in a pathophysiological context.

PMID- 15967817
TI  - No audible wheezing: nuggets and conundrums from mouse asthma models.
AB  - Mouse models of T helper type 2 (Th2) cell-biased pulmonary inflammation have
      elucidated mechanisms of sensitization, cell traffic, and induced airway
      hyperresponsiveness (AHR). Nonetheless, most mice lack intrinsic AHR, a central
      property of human asthma, and disparities persist regarding the contributions of
      eosinophils and mast cells and the sensitivity to induced AHR in the commonly
      used mouse strains. We suggest that these discordances, reflecting methodological
      and genetic differences, may be informative for understanding heterogeneity of
      human asthma.

PMID- 15967818
TI  - Nonhuman primate models of asthma.
AB  - Asthma is a complex human disease that does not have an accurate counterpart in
      any common model organism. Most of our understanding of the immune mechanisms
      underlying asthma comes from studies in man and mouse. However, there are
      fundamental differences between the spontaneous disease in man and the
      experimentally induced counterparts in mice. We advocate more extensive use of
      nonhuman primate asthma models to reconcile these differences between man and
      mouse.

PMID- 15967819
TI  - Antiviral T cell responses: phalanx or multipronged attack?
AB  - Around 700 BCE, a new military formation called the phalanx was established in
      ancient Greece: a tight column of heavy infantry carrying long spears, or pikes,
      used in a single prong of attack. Later, in the battle of Marathon described by
      Herodotus, the Greeks learned the advantages of multipronged attacks, a strategy
      still used in modern warfare. Is the immune system similar in its approach to
      combatting pathogens or tumors?

PMID- 15967820
TI  - Interleukin (IL)-4 inhibits IL-10 to promote IL-12 production by dendritic cells.
AB  - Interleukin (IL)-4 is known to be the most potent cytokine that can initiate Th2
      cell differentiation. Paradoxically, IL-4 instructs dendritic cells (DCs) to
      promote Th1 cell differentiation. We investigated the mechanisms by which IL-4
      directs CD4 T cells toward the Th1 cell lineage. Our study demonstrates that the
      IL-4-mediated induction of Th1 cell differentiation requires IL-10 production by
      DCs. IL-4 treatment of DCs in the presence of lipopolysaccharide or CpG resulted
      in decreased production of IL-10, which was accompanied by enhanced IL-12
      production. In IL-10-deficient DCs, the level of IL-12 was greatly elevated and,
      more importantly, the ability of IL-4 to up-regulate IL-12 was abrogated.
      Interestingly, IL-4 inhibited IL-10 production by DCs but not by B cells. The
      down-regulation of IL-10 gene expression by IL-4 depended on Stat6 and was at
      least partly caused by decreased histone acetylation of the IL-10 promoter. These
      data indicate that IL-4 plays a key role in inducing Th1 cell differentiation by
      instructing DCs to produce less IL-10.

PMID- 15967821
TI  - A chromosomally integrated bacteriophage in invasive meningococci.
AB  - Cerebrospinal meningitis is a feared disease that can cause the death of a
      previously healthy individual within hours. Paradoxically, the causative agent,
      Neisseria meningitidis, is a common inhabitant of the human nasopharynx, and as
      such, may be considered a normal, commensal organism. Only in a small proportion
      of colonized people do the bacteria invade the bloodstream, from where they can
      cross the blood-brain barrier to cause meningitis. Furthermore, most
      meningococcal disease is caused by bacteria belonging to only a few of the
      phylogenetic groups among the large number that constitute the population
      structure of this genetically variable organism. However, the genetic basis for
      the differences in pathogenic potential remains elusive. By performing whole
      genome comparisons of a large collection of meningococcal isolates of defined
      pathogenic potential we brought to light a meningococcal prophage present in
      disease-causing bacteria. The phage, of the filamentous family, excises from the
      chromosome and is secreted from the bacteria via the type IV pilin secretin.
      Therefore, this element, by spreading among the population, may promote the
      development of new epidemic clones of N. meningitidis that are capable of
      breaking the normal commensal relationship with humans and causing invasive
      disease.

PMID- 15967822
TI  - IFN-gamma production by alloantigen-reactive regulatory T cells is important for
      their regulatory function in vivo.
AB  - The significance of cytokine production by CD4(+) regulatory T (T reg) cells
      after antigen exposure in vivo and its impact on their regulatory activity
      remains unclear. Pretreatment with donor alloantigen under the cover of anti-CD4
      therapy generates alloantigen reactive T reg cells that can prevent rejection of
      donor-specific skin grafts that are mediated by naive CD45RB(high)CD4(+) T cells.
      To examine the kinetics and importance of cytokine gene transcription by such
      alloantigen-reactive T reg cells, pretreated mice were rechallenged with donor
      alloantigen in vivo. CD25(+)CD4(+) T cells, but not CD25(-)CD4(+) T cells, showed
      a fivefold increase in IFN-gamma mRNA expression within 24 h of re-encountering
      alloantigen in vivo. This expression kinetic was highly antigen-specific and was
      of functional significance. Neutralizing IFN-gamma at the time of cotransfer of
      alloantigen reactive T reg cells, together with CD45RB(high)CD4(+) effector T
      cells into Rag(-/-) skin graft recipients, resulted in skin graft necrosis in all
      recipients; the generation and function of alloantigen-reactive T reg cells was
      impaired dramatically in IFN-gamma-deficient mice. These data support a unique
      role for IFN-gamma in the functional activity of alloantigen-reactive T reg cells
      during the development of operational tolerance to donor alloantigens in vivo.

PMID- 15967823
TI  - C4b-binding protein binds to necrotic cells and DNA, limiting DNA release and
      inhibiting complement activation.
AB  - After cell death, via apoptosis or necrosis, the uptake of dead cells by
      neighboring cells or phagocytes prevents the release of intracellular content. An
      array of molecules, including initiation molecules of the complement system, are
      involved in marking dead cells for uptake. After binding of these molecules,
      complement activation takes place, which when uncontrolled might result in a
      proinflammatory state. In the current study we demonstrate that complement
      inhibitor, C4b-binding protein (C4BP), binds strongly to necrotic cells,
      irrespective of the cell type used or the method of induction. After binding of
      the C4BP-protein S (PS) complex to necrotic cells via PS-phosphatidylserine and
      C4BP-DNA interactions, C4BP-PS inhibits complement activation on these cells.
      C4BP binds DNA via a patch of positively charged amino acids, mainly on the
      second complement control domain of the C4BP alpha-chain (affinity constant: 190
      nM). Furthermore, C4BP limits DNA release from necrotic cells and inhibits DNA
      mediated complement activation in solution. The C4BP-necrotic cell interaction
      also occurs in vivo as necrotic areas of arteriosclerotic plaques and of various
      cancers stain strongly positive for C4BP. This study describes a novel mechanism
      in which C4BP limits the inflammatory potential of necrotic cells.

PMID- 15967824
TI  - Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause
      defects in hematopoiesis and in thymocyte apoptosis.
AB  - The proapoptotic members of the Bcl-2 family can be subdivided into members that
      contain several Bcl-2 homology (BH) domains and those that contain only the BH3
      domain. Although it is known that BH3-only proteins and the multi-BH domain
      proteins, Bak and Bax, are essential for programmed cell death, the overlapping
      role of these two subgroups has not been examined in vivo. To investigate this,
      we generated Bak/Bim and Bax/Bim double deficient mice. We found that although
      Bax-/-Bim-/-, but not Bak-/-Bim-/-, mice display webbed hind and front paws and
      malocclusion of the incisors, both groups of mice present with dysregulated
      hematopoiesis. Combined loss of Bak and Bim or Bax and Bim causes defects in
      myeloid and B-lymphoid development that are more severe than those found in the
      single knock-out mice. Bak-/-Bim-/- mice have a complement of thymocytes that
      resembles those in control mice, whereas Bax-/-Bim-/- mice are more similar to
      Bim-/- mice. However, thymocytes isolated from Bak-/-Bim-/- or Bax-/-Bim-/- mice
      are markedly more resistant to apoptotic stimuli mediated by the intrinsic
      pathway as compared with thymocytes from single-knockout mice. These data suggest
      an essential overlapping role for Bak or Bax and Bim in the intrinsic apoptotic
      pathway.

PMID- 15967825
TI  - Sequential activation of NKT cells and NK cells provides effective innate
      immunotherapy of cancer.
AB  - The CD1d reactive glycolipid, alpha-galactosylceramide (alpha-GalCer), potently
      activates T cell receptor-alpha type I invariant NKT cells that secondarily
      stimulate the proliferation and activation of other leukocytes, including NK
      cells. Here we report a rational approach to improving the antitumor activity of
      alpha-GalCer by using delayed interleukin (IL)-21 treatment to mature the alpha
      GalCer-expanded pool of NK cells into highly cytotoxic effector cells. In a
      series of experimental and spontaneous metastases models in mice, we demonstrate
      far superior antitumor activity of the alpha-GalCer/IL-21 combination above
      either agent alone. Superior antitumor activity was critically dependent upon the
      increased perforin-mediated cytolytic activity of NK cells. Transfer of alpha
      GalCer-pulsed dendritic cells (DCs) followed by systemic IL-21 caused an even
      more significant reduction in established (day 8) metastatic burden and prolonged
      survival. In addition, this combination prevented chemical carcinogenesis more
      effectively. Combinations of IL-21 with other NK cell-activating cytokines, such
      as IL-2 and IL-12, were much less effective in the same experimental metastases
      models, and these cytokines did not substitute effectively for IL-21 in
      combination with alpha-GalCer. Overall, the data suggest that NK cell antitumor
      function can be enhanced greatly by strategies that are designed to expand and
      differentiate NK cells via DC activation of NKT cells.

PMID- 15967826
TI  - Repertoire, diversity, and differentiation of specific CD8 T cells are associated
      with immune protection against human cytomegalovirus disease.
AB  - To determine the correlates of immune recovery from active human CMV (HCMV)
      disease, we compared the antigenic repertoire, diversity, magnitude, and
      differentiation of HCMV-specific CD8+ T cells in HIV-HCMV coinfected subjects
      with no, cured, or active HCMV disease and in healthy HIV-negative HCMV-positive
      controls. ELISPOT-IFN-gamma assays using peptide pools spanning the pp65 and
      immediate early 1 (IE1) HCMV proteins showed that HCMV-specific CD8+ T cells had
      a significantly broader antigenic repertoire and greater diversity in HIV
      positive patients controlling HCMV replication than in those with active HCMV
      disease, but the magnitude of the CD8 T cell response did not differ between the
      different groups. HCMV-specific T cells mainly were focused against IE1 during
      the short-term recovery from retinitis, and switched toward pp65 during long-term
      recovery. HCMV-specific T cells displaying an "early" (CD8+CD27+CD28+) and
      "intermediate" (CD8+CD27-CD28+) differentiation phenotype were increased
      significantly during long-term recovery compared with other HIV-positive patients
      and were nearly undetectable during active HCMV disease. HCMV-specific T cells
      with a "late" (CD8+CD27-28-) differentiation phenotype predominated in all cases.
      Therefore, restoration of immune protection against HCMV after active HCMV
      disease in immunodeficient individuals is associated with enlarged repertoire and
      diversity, and with early differentiation of virus-specific CD8+ T cells, thus
      defining immune correlates of protection against diseases caused by persistent
      viruses.

PMID- 15967827
TI  - B cells from hyper-IgM patients carrying UNG mutations lack ability to remove
      uracil from ssDNA and have elevated genomic uracil.
AB  - The generation of high-affinity antibodies requires somatic hypermutation (SHM)
      and class switch recombination (CSR) at the immunoglobulin (Ig) locus. Both
      processes are triggered by activation-induced cytidine deaminase (AID) and
      require UNG-encoded uracil-DNA glycosylase. AID has been suggested to function as
      an mRNA editing deaminase or as a single-strand DNA deaminase. In the latter
      model, SHM may result from replicative incorporation of dAMP opposite U or from
      error-prone repair of U, whereas CSR may be triggered by strand breaks at abasic
      sites. Here, we demonstrate that extracts of UNG-proficient human B cell lines
      efficiently remove U from single-stranded DNA. In B cell lines from hyper-IgM
      patients carrying UNG mutations, the single-strand-specific uracil-DNA
      glycosylase, SMUG1, cannot complement this function. Moreover, the UNG mutations
      lead to increased accumulation of genomic uracil. One mutation results in an
      F251S substitution in the UNG catalytic domain. Although this UNG form was fully
      active and stable when expressed in Escherichia coli, it was mistargeted to
      mitochondria and degraded in mammalian cells. Our results may explain why SMUG1
      cannot compensate the UNG2 deficiency in human B cells, and are fully consistent
      with the DNA deamination model that requires active nuclear UNG2. Based on our
      findings and recent information in the literature, we present an integrated model
      for the initiating steps in CSR.

PMID- 15967828
TI  - Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen
      specific CD4+ T cells.
AB  - Dendritic cells (DCs) are essential antigen-presenting cells for the induction of
      T cell immunity against pathogens such as human immunodeficiency virus (HIV)-1.
      At the same time, HIV-1 replication is strongly enhanced in DC-T cell clusters,
      potentially undermining this process. We found that immature CD123(+)
      plasmacytoid DCs (PDCs) and CD11c(+) myeloid DCs (MDCs) were susceptible to both
      a CCR5- and a CXCR4-using HIV-1 isolate in vitro and were able to efficiently
      transfer that infection to autologous CD4(+) T cells. Soon after HIV-1 exposure,
      both PDCs and MDCs were able to transfer the virus to T cells in the absence of a
      productive infection. However, once a productive infection was established in the
      DCs, newly synthesized virus was predominantly spread to T cells. HIV-1 exposure
      of the MDCs and PDCs did not inhibit their ability to present cytomegalovirus
      (CMV) antigens and activate CMV-specific memory T cells. As a result, both PDCs
      and MDCs preferentially transmitted HIV-1 to the responding CMV antigen-specific
      CD4(+) T cells rather than to nonresponding T cells. This suggests that the
      induction of antigen-specific T cell responses by DCs, a process crucial to
      immune defense, can lead to preferential HIV-1 infection and the deletion of
      responding CD4(+) T cells.

PMID- 15967829
TI  - FDA drug approval summary: pemetrexed for injection (Alimta) for the treatment of
      non-small cell lung cancer.
AB  - On August 19, 2004, pemetrexed for injection (Alimta); Eli Lilly and Company,
      Indianapolis, IN, http://www.lilly.com) received accelerated approval as
      monotherapy for the treatment of patients with locally advanced or metastatic non
      small cell lung cancer (NSCLC) who had received prior chemotherapy. Approval was
      primarily based on a single, controlled, unblinded trial. Five hundred seventy
      one protocol-eligible patients were randomized to receive either pemetrexed or
      docetaxel (Taxotere); Aventis Pharmaceuticals Inc., Bridgewater, NJ,
      http://www.aventispharmaus.com). The primary efficacy end point was overall
      survival. The median survival times were 8.3 months in the pemetrexed arm and 7.9
      months in the docetaxel arm. Neither superiority nor noninferiority for overall
      survival could be demonstrated, the latter because a reliable and consistent
      survival effect of docetaxel could not be estimated and because of significant
      crossover of pemetrexed-treated patients to docetaxel after tumor progression.
      Comparable response rates, 9.1% for pemetrexed and 8.8% for docetaxel, times to
      progressive disease, and progression-free survival times supported the conclusion
      that an effect of pemetrexed on survival was reasonably likely, however. In
      addition, pemetrexed was felt to have a more favorable safety profile than
      docetaxel. Of greatest importance, pemetrexed caused significantly less
      neutropenia, febrile neutropenia, neutropenic infections, and need for
      granulocyte/macrophage colony-stimulating factors.

PMID- 15967830
TI  - Breast cancer: a tale of two centuries: with implications for understanding
      cancer metastasis and cancer stem cell biology.

PMID- 15967831
TI  - Conceptual and practical implications of breast tissue geometry: toward a more
      effective, less toxic therapy.
AB  - Mathematics provides greater understanding of the complex process of
      tumorigenesis. Based on the Gompertzian phenomenon and the Norton-Simon
      hypothesis, enhanced cell kill can be obtained through a greater chemotherapy
      dose rate. Results from the 1995 Bonadonna et al. study and the CALGB/Intergroup
      C9741 study demonstrated that patients in the dose-dense arms had significantly
      longer disease-free survival and overall survival. Because of the demonstrated
      applicability of Gompertzian kinetics, attention has been turned to the etiology
      of the Gompertzian curve. Breast tumor dimensions, as with all tissue dimensions
      in biology, can be calculated by fractals. A less cell-dense tissue usually has a
      lower fractal dimension than a tissue with more cells (i.e., a higher cell
      density is usually due to a higher fractal dimension). Density is the number of
      cells divided by the tissue volume. When allowed to grow, the density of a tissue
      with a lower fractal dimension drops quickly. However, a tumor, since it has a
      higher fractal mass dimension, maintains a high density as it grows bigger,
      resulting in a more rapid growth rate and a larger final size. Fractal dimensions
      of infiltrating ductal adenocarcinomas of the breast are high (i.e., 2.98), which
      results in a very dense tissue compared with normal breast tissue (with a fractal
      dimension of about 2.25). As expected, the higher fractal dimension results in a
      high rate of growth. The reason for this high fractal dimension is that breast
      cancer can be considered as a conglomerate of many small Gompertzian tumors, each
      of which has a high cell density and hence ratio of mitosis to apoptosis. In
      mathematical terms, each component of the conglomerate can be considered a small
      metastasis in itself. Thus, the primary tumor is composed of multiple self
      metastases that form around a seed from the tumor to itself. Conventional
      thinking is that cancers metastasize because they are large, but in fact it may
      be that they are large because they are self-metastatic. Many genes are
      associated with the biology of metastasis; these include: A) obligatory cancer
      genes (most of which regulate mitosis and mitotic rate); B) genes relating to
      self-metastasis and growth of tumors at local sites, conferring the ability to
      invade and grow with high cell density; and C) genes that relate to the ability
      of the cancer to metastasize to distant areas. Additionally, fibroblasts may send
      out abnormal growth signals causing abnormal breast tissue growth. Consequently,
      we are not only dealing with abnormal cancer cells, but also with the tissue that
      surrounds them, or the microenvironment, that is, the "Smith-Bissell" model.
      These new insights may lead us to change the thrust of our attack from genes
      involved in mitosis to those involved in metastasis, including metastasis to
      self, and to use and further improve dose-dense regimens.

PMID- 15967832
TI  - VEGF-targeted therapy: therapeutic potential and recent advances.
AB  - After over 30 years of theorizing, the use of angiogenesis inhibitors as
      anticancer therapy has finally moved from the realm of research to reality.
      Normal adult vasculature is generally quiescent in nature, with endothelial cells
      dividing approximately every 10 years. In contrast, the growth of tumors requires
      constant vascular growth and remodeling in order for solid tumors to grow beyond
      1-2 mm(3) in size. Vascular endothelial growth factor (VEGF) and its receptors
      are key regulators of the process of angiogenesis, which makes them attractive
      therapeutic targets. A multitude of VEGF-targeted inhibitory agents are currently
      being investigated for the treatment of cancer. This review article focuses on
      recent developments in the use of angiogenesis inhibitors for the treatment of
      breast, lung, and colorectal cancers.

PMID- 15967833
TI  - A phase II study of epirubicin and thalidomide in unresectable or metastatic
      hepatocellular carcinoma.
AB  - BACKGROUND: The median survival time for patients with unresectable
      hepatocellular carcinoma (HCC) is <6 months, and no effective standard systemic
      chemotherapy is available. Both epirubicin (Ellence); Pfizer Pharmaceuticals, New
      York, NY, http://www.pfizer.com) and thalidomide (Thalomid); Celgene Corporation,
      Warren, NJ, http://www.celgene.com) have reported activity for HCC as single
      agents, and they have different mechanisms of action and nonoverlapping
      toxicities. Therefore, we performed a phase II study using the combination of
      epirubicin and thalidomide in patients with unresectable and metastatic HCC.
      METHODS: Nineteen patients with measurable, unresectable, or metastatic HCC were
      enrolled. All patients were required to have adequate major organ function and
      performance status. The treatment consisted of weekly epirubicin at a dose of 20
      mg/m(2) administered i.v. and daily thalidomide at a dose of 200 mg orally given
      as a 3-weeks-on/1-week-off schedule. Intrapatient dose escalation of thalidomide
      was allowed every 2 weeks up to 800 mg daily as long as tolerated. Physical
      examinations, toxicity assessments, and serum chemistry analyses were performed
      weekly, and tumor measurements were conducted every 8 weeks. RESULTS: All 19
      patients enrolled into the study were evaluable for toxicity assessment and 17
      patients were evaluable for response assessment. A total of 71 cycles of
      chemotherapy was administered, with a median of two cycles administered to each
      patient (range 1-14). No complete or partial responses were observed. Seven
      patients (41%) had stable disease, with a median duration of 6 months (range 5
      14). The median survival time for all 19 patients was 196 days (95% confidence
      interval 93-302). The treatment was generally well tolerated. Treatment-related
      toxicities included constipation (grade 3, 5%; grade 2, 37%; grade 1, 21%),
      fatigue (grade 3, 5%; grade 2, 42%), and sensory neuropathy (grade 2, 5%; grade
      1, 32%). Four patients required dose reductions of thalidomide due to treatment
      related toxicities, and the median tolerated dose of thalidomide was 200 mg
      daily. CONCLUSIONS: The combination of epirubicin and thalidomide was well
      tolerated when administered in the schedule used in this study. This regimen has
      limited activity in HCC, with some patients achieving stable disease and clinical
      benefit. There is a need for defining more effective systemic therapies for HCC.

PMID- 15967834
TI  - Treatment of small cell lung cancer in the elderly.
AB  - Small cell lung cancer (SCLC) accounts for approximately 20% of lung carcinomas.
      Chemotherapy is the cornerstone of treatment for SCLC. In limited disease, the
      median survival time is about 12-16 months, with a 4%-5% long-term survival rate;
      in extensive disease the median survival time is 7-11 months. More than 50% of
      lung cancer patients are diagnosed when they are over the age of 65, and about
      30% are over 70. Elderly patients tolerate chemotherapy poorly compared with
      their younger counterparts, because of age-related progressive reductions in
      organ function and comorbidities. The standard therapy for limited disease is
      combined chemoradiotherapy, followed by prophylactic brain irradiation for
      patients achieving complete responses. In the elderly, the addition of
      radiotherapy to chemotherapy must be carefully evaluated, considering the slight
      survival benefit and potential for substantial toxicity incurred with this
      treatment. The best approach is to design clinical trials that specifically
      include geriatric assessment to develop active and well-tolerated chemotherapy
      regimens for elderly SCLC patients. Survival improvement for SCLC patients
      requires a better understanding of tumor biology and the subsequent development
      of novel therapeutic strategies. Several targeted agents have been introduced
      into clinical trials in SCLC, but a minority of these new agents offers a promise
      of improved outcomes, and negative results are reported more commonly than
      positive ones. This review focuses on the main issues in the treatment of elderly
      SCLC patients.

PMID- 15967835
TI  - AIDS-related malignancies: emerging challenges in the era of highly active
      antiretroviral therapy.
AB  - Human immunodeficiency virus (HIV)-infected patients are at increased risk of
      developing cancer, particularly in the later stages of acquired immune deficiency
      syndrome (AIDS). Despite the advent of highly active anti-retroviral therapy
      (HAART), malignancy in this population is a leading cause of morbidity and
      mortality. Kaposi's sarcoma (KS) and AIDS-related non-Hodgkin's lymphoma (ARL)
      are the most common AIDS-defining malignancies. AIDS-related KS varies from
      minimal to fulminant disease. Treatment decisions for AIDS-related KS are guided
      largely by the presence and extent of symptomatic disease. In addition to HAART,
      excellent treatments exist for both localized disease (topical gel, radiotherapy,
      and intralesional therapy) and advanced disease (liposomal anthracyclines,
      paclitaxel). Novel therapies that have become available to treat AIDS-related KS
      include angiogenesis inhibitors and antiviral agents. ARL comprises a
      heterogeneous group of malignancies. With the immune restoration afforded by
      HAART, standard-dose chemotherapies now can be safely administered to treat ARL
      with curative intent. The role of analogous treatments used in HIV-negative
      patients, including monoclonal antibodies and autologous stem cell
      transplantation, requires further clarification in HIV-positive patients. HIV
      infected patients also appear to be at increased risk for developing certain non
      AIDS-defining cancers, such as Hodgkin's lymphoma and multiple myeloma. Although
      the optimal treatment of these neoplasms is at present uncertain, recent advances
      in chemotherapy, antiretroviral drugs, and supportive care protocols are allowing
      for more aggressive management of many of the AIDS-related cancers. This article
      provides an up-to-date review of the epidemiology, pathogenesis, clinical
      features, and treatment of various AIDS-related malignancies that are likely to
      be encountered by an oncologist practicing in the current HAART era.

PMID- 15967836
TI  - Risk models for predicting chemotherapy-induced neutropenia.
AB  - Neutropenia and its complications, including febrile neutropenia, are major dose
      limiting toxicities of systemic cancer chemotherapy. A number of studies have
      attempted to identify risk factors for neutropenia and its consequences to
      develop predictive models capable of identifying patients at greater risk for
      such complications and to guide more effective and cost-effective applications of
      the colony-stimulating factors. A systematic review of the literature showed that
      age, performance status, nutritional status, chemotherapy dose intensity, and low
      baseline blood cell counts were associated with the risk of severe and febrile
      neutropenia or reduced chemotherapy dose intensity in multivariate analysis in
      two or more studies. Similarly, age, diagnosis of leukemia or lymphoma, high
      temperature or low blood pressure at admission, and i.v. site infection along
      with low blood cell counts and organ dysfunction were associated with serious
      medical complications of febrile neutropenia, including bacteremia and death. The
      available risk model studies, however, had several limitations, including
      retrospective analyses of small study populations lacking independent validation,
      frequent missing values, and differences in the predictive factors considered. To
      overcome the limitations of previous studies, efforts are under way to develop
      and validate risk models based on large prospective studies in representative
      populations of patients receiving systemic chemotherapy.

PMID- 15967837
TI  - Assessing the clinical benefits of erythropoietic agents using area under the
      hemoglobin change curve.
AB  - INTRODUCTION: In assessing erythropoietic agents for chemotherapy-induced anemia,
      traditional single time-point end points (e.g., hematopoietic response [HR]) fail
      to reflect clinical benefits over the entire therapy course. Area under the
      hemoglobin change curve (Hb AUC) is introduced as an alternative measure, and its
      reliability, clinical significance, and superiority are assessed. METHODS: Using
      data from a phase IV open-label epoetin alfa (EPO) trial, we tested Hb AUC
      reliability by comparing its values derived from primary patient data with those
      derived from aggregated data. Clinical significance of the Hb AUC was
      investigated in three phase IV EPO trials by examining the linear relationship
      between Hb AUC quartiles and established clinical end points. The superiority of
      the Hb AUC over HR in its association with blood transfusion was tested through
      logistic regressions and area under the receiver operating characteristic (ROC)
      curve analysis. RESULTS: The Hb AUC values derived from patient and aggregated
      data were similar. Strong and statistically significant linear trends of
      decreasing transfusion requirements, increasing quality-of-life improvements, and
      decreasing time to HR were found across Hb AUC quartiles. The Hb AUC rendered the
      HR variable insignificant when both were present in the same model. Area under
      the ROC curve analysis supported the superior performance of the Hb AUC.
      CONCLUSIONS: We found that the Hb AUC is an objective, reliable, clinically
      meaningful, and comprehensive summary statistic that may be used to quantify
      clinical benefits for patients receiving erythropoietic agents. Further
      prospective validation of the Hb AUC metric is recommended.

PMID- 15967838
TI  - Learning to cope: how far is too close?
AB  - Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at
      Massachusetts General Hospital, founded The Kenneth B. Schwartz Center. The
      Schwartz Center is a nonprofit organization dedicated to advancing compassionate
      health care delivery, with the goal of providing hope to patients and support to
      caregivers. The Schwartz Center Rounds is a monthly multidisciplinary forum where
      caregivers reflect on important psychosocial issues faced by patients, families,
      and caregivers, and gain insight and support from fellow staff members. The case
      is presented of a patient with a precipitous decline in health due to rapidly
      progressive, metastatic non-small cell lung cancer. The discussion at Schwartz
      Center Rounds centers on oncologists' feelings of failure and coping mechanisms
      when dealing with patients' deaths. This discussion is followed by a first-year
      oncology fellow's reaction to caring for this and other terminally ill patients.
      Then, to provide a broader framework in which to understand these issues, the
      emotional cost and measurable benefit of close relationships with patients is
      investigated. To conclude, further educational initiatives are advocated to
      assist both physicians-in-training and more senior clinicians in dealing with the
      difficult issues that arise when caring for very ill and dying patients.

PMID- 15967839
TI  - Development of multiple myeloma in a patient with chronic myeloid leukemia after
      treatment with imatinib mesylate.

PMID- 15967841
TI  - Estradiol-mediated endothelial nitric oxide synthase association with heat shock
      protein 90 requires adenosine monophosphate-dependent protein kinase.
AB  - BACKGROUND: Estradiol activates endothelial nitric oxide synthase (eNOS) by
      mechanisms that involve estrogen receptor-alpha (ERalpha), protein kinase B/Akt,
      mitogen-activated protein kinases, and heat shock protein 90 (HSP90). Recently,
      AMP-activated protein kinase (AMPK), an enzyme that plays a crucial role in
      cellular adaptation to metabolic stress, has been implicated in physiological
      eNOS activation by the hormones adiponectin and insulin. We therefore
      investigated whether AMPK is activated by estradiol in endothelial cells and
      plays a role in estradiol-induced eNOS activation. METHODS AND RESULTS: Porcine
      aortic endothelial cells exhibited time- and concentration-dependent AMPK
      activation as determined by phosphorylation of AMPK and its downstream target
      acetyl coenzyme A carboxylase in response to estradiol (1 nmol/L to 10
      micromol/L, 1 to 30 minutes). AMPK activation by estradiol was independent of
      both AMP levels and ERalpha but required estradiol conversion to its catechol
      metabolites. Estradiol treatment increased eNOS catalytic activity, an effect
      that was largely reversed when endothelial cells were infected with an AMPK
      dominant-negative adenovirus. However, inhibition of AMPK did not alter estradiol
      induced eNOS phosphorylation at serine 1177 or threonine 495 but decreased eNOS
      interaction with HSP90. Consistent with this observation, blood vessels from
      alpha1-AMPK-null mice exhibited defective eNOS-mediated NO production in response
      to estradiol. CONCLUSIONS: Taken together, these data indicate that AMPK activity
      is essential for estradiol-induced eNOS activation via the promotion of eNOS
      interaction with HSP90. These data point to a novel role for AMPK in modulating
      endothelial cell NO bioactivity and HSP90 function.

PMID- 15967842
TI  - High incidence of sudden cardiac death with conduction disturbances and atrial
      cardiomyopathy caused by a nonsense mutation in the STA gene.
AB  - BACKGROUND: The STA gene encodes emerin and is one of the genes that is affected
      in Emery-Dreifuss muscular dystrophy (EDMD). Although it has been reported that
      EDMD caused by the STA gene mutation is associated with X-linked recessive
      inheritance, the genotype-phenotype correlations, with special reference to
      cardiac manifestations, are not well defined. METHODS AND RESULTS: We identified
      16 carriers (7 male and 9 female) with a nonsense mutation in exon 6 of the STA
      gene in 2 EDMD families. Pacemakers were required for treatment of
      bradyarrhythmias in all 7 male carriers and in 2 of the 9 female carriers. In
      addition, 2 of the 9 female carriers displayed atrial fibrillation. In these 2
      families, 3 males without pacemaker implantation, who were not tested
      genetically, had died suddenly. In these family members, the majority of carriers
      with the mutation had not been clinically diagnosed as having EDMD before genetic
      testing because of extremely mild or nonexistent skeletal myopathy. CONCLUSIONS:
      EDMD caused by this mutation is characterized by atypical clinical features and
      incomplete penetrance of the clinical phenotype and may result in serious cardiac
      complications, including sudden death. Approaches to preventing possible sudden
      death in carriers with the STA gene mutation require further study.

PMID- 15967843
TI  - Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac
      dysfunction, and premature death in scavenger receptor class B type I-deficient,
      hypomorphic apolipoprotein ER61 mice.
AB  - BACKGROUND: Normal chow (low fat)-fed mice deficient in both the HDL receptor SR
      BI and apolipoprotein E (SR-BI/apoE dKO) provide a distinctive model of coronary
      heart disease (CHD). They exhibit early-onset hypercholesterolemia characterized
      by unesterified cholesterol-rich abnormal lipoproteins (lamellar/vesicular and
      stacked discoidal particles), occlusive coronary atherosclerosis, spontaneous
      myocardial infarction, cardiac dysfunction, and premature death ( approximately 6
      weeks of age). Mice in which similar features of CHD could be induced with a
      lipid-rich diet would represent a powerful tool to study CHD. METHODS AND
      RESULTS: To generate a diet-inducible model of CHD, we bred SR-BI-deficient (SR
      BI KO) mice with hypomorphic apolipoprotein E mice (ApoeR61(h/h)) that express
      reduced levels of an apoE4-like murine apoE isoform and exhibit diet-induced
      hypercholesterolemia. When fed a normal chow diet, SR-BI KO/ApoeR61(h/h) mice did
      not exhibit early-onset atherosclerosis or CHD; the low expression level of the
      apoE4-like murine apoE was atheroprotective and cardioprotective. However, when
      fed an atherogenic diet rich in fat, cholesterol, and cholate, they rapidly
      developed hypercholesterolemia, atherosclerosis, and CHD, a response strikingly
      similar to that of SR-BI/apoE dKO mice fed a chow diet, and they died 32+/-6 days
      (50% mortality) after initiation of the high-fat feeding. CONCLUSIONS: The SR-BI
      KO/ApoeR61(h/h) mouse is a new model of diet-induced occlusive coronary
      atherosclerosis and CHD (myocardial infarction, cardiac dysfunction and premature
      death), allowing control of the age of onset, duration, severity, and possibly
      regression of disease. Thus, SR-BI KO/ApoeR61(h/h) mice have the potential to
      contribute to our understanding of CHD and its prevention and treatment.

PMID- 15967844
TI  - Late loss in lumen diameter and binary restenosis for drug-eluting stent
      comparison.
AB  - BACKGROUND: Published rates of coronary restenosis have fallen below 10% in drug
      eluting stent trials. Early evaluations of new stents have used continuous end
      points that are presumed surrogates for restenosis, but the generalizability and
      power of such end points have not been examined systematically. METHODS AND
      RESULTS: We examined the relationship between incremental changes in observed
      late loss in lumen diameter and the probability of restenosis using reported late
      loss from 22 published trials of various types of stents (bare-metal, drug
      eluting, and small-vessel stents). Next, the power of late loss differences was
      compared with that of corresponding binary restenosis rates. The relationship
      between mean late loss and its SD was linear and did not vary with stent type
      (drug-eluting or bare-metal) or vessel diameter. At all levels of late loss
      examined (0 to 1 mm), incremental changes were associated with increasing
      restenosis risk (with an increasing magnitude of effect at higher levels of late
      loss). The power to detect a treatment effect was greater for late loss than for
      binary angiographic restenosis (> or =32% relative increase in power, > or =24%
      absolute increase for late loss between 0.2 and 0.6 mm). CONCLUSIONS: Late loss
      is monotonically related to restenosis risk in published stent trials. It is a
      generalizable and powerful angiographic end point in early or small trials of new
      drug-eluting stents.

PMID- 15967845
TI  - Gene profiling in atherosclerosis reveals a key role for small inducible
      cytokines: validation using a novel monocyte chemoattractant protein monoclonal
      antibody.
AB  - BACKGROUND: Pathological aspects of atherosclerosis are well described, but gene
      profiles during atherosclerotic plaque progression are largely unidentified.
      METHODS AND RESULTS: Microarray analysis was performed on mRNA of aortic arches
      of ApoE-/- mice fed normal chow (NC group) or Western-type diet (WD group) for 3,
      4.5, and 6 months. Of 10 176 reporters, 387 were differentially (>2x) expressed
      in at least 1 group compared with a common reference (ApoE-/-, 3- month NC
      group). The number of differentially expressed genes increased during plaque
      progression. Time-related expression clustering and functional grouping of
      differentially expressed genes suggested important functions for genes involved
      in inflammation (especially the small inducible cytokines monocyte
      chemoattractant protein [MCP]-1, MCP-5, macrophage inflammatory protein [MIP]
      1alpha, MIP-1beta, MIP-2, and fractalkine) and matrix degradation (cathepsin-S,
      matrix metalloproteinase-2/12). Validation experiments focused on the gene
      cluster of small inducible cytokines. Real-time polymerase chain reaction
      revealed a plaque progression-dependent increase in mRNA levels of MCP-1, MCP-5,
      MIP-1alpha, and MIP-1beta. ELISA for MCP-1 and MCP-5 showed similar results.
      Immunohistochemistry for MCP-1, MCP-5, and MIP-1alpha located their expression to
      plaque macrophages. An inhibiting antibody for MCP-1 and MCP-5 (11K2) was
      designed and administered to ApoE-/- mice for 12 weeks starting at the age of 5
      or 17 weeks. 11K2 treatment reduced plaque area and macrophage and CD45+ cell
      content and increased collagen content, thereby inducing a stable plaque
      phenotype. CONCLUSIONS: Gene profiling of atherosclerotic plaque progression in
      ApoE-/- mice revealed upregulation of the gene cluster of small inducible
      cytokines. Further expression and in vivo validation studies showed that this
      gene cluster mediates plaque progression and stability.

PMID- 15967846
TI  - Changes in ventricular size and function in patients treated with valsartan,
      captopril, or both after myocardial infarction.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have been shown to
      attenuate left ventricular (LV) enlargement in association with reducing
      mortality after myocardial infarction (MI). Preclinical data suggest that
      angiotensin receptor blockers (ARBs) may have similar structural and functional
      effects after MI. The Valsartan in Acute Myocardial Infarction (VALIANT) Echo
      study was designed to test the hypothesis that the ARB valsartan, either alone or
      in combination with captopril, could attenuate progressive LV enlargement or
      improve LV ejection fraction to a greater extent than captopril alone. METHODS
      AND RESULTS: Six hundred ten patients enrolled in the main VALIANT study who
      experienced MI and evidence of LV dysfunction, heart failure, or both were
      enrolled in the VALIANT Echo study. Patients were randomized to receive valsartan
      160 mg PO BID, captopril 50 mg PO TID, or valsartan 80 mg PO BID plus captopril
      50 mg PO TID between 1 and 10 days after MI. Six hundred three patients had
      echocardiograms of sufficient quality for quantitative analysis. Echocardiograms
      were digitized, and endocardial borders were traced manually from 2 short-axis
      and 2 apical views. Ventricular volumes, ejection fractions, combined areas, and
      infarct segment length were measured, and changes in echocardiographic measures
      from baseline to 20 months were compared between treatment groups. Baseline
      clinical and echocardiographic characteristics were similar in the 3 treatment
      arms. The changes from baseline to 20 months in all echocardiographic parameters
      were similar in all 3 treatment arms. Baseline echocardiographic measures of
      ejection fraction, end-diastolic volume, and infarct segment length were highly
      predictive of outcomes including total mortality, death or hospitalization for
      heart failure, or death or any cardiovascular event (heart failure, MI, stroke,
      resuscitated sudden death), even after adjustment for known covariates.
      CONCLUSIONS: Treatment with the ACE inhibitor captopril, valsartan, or the
      combination of captopril plus valsartan resulted in similar changes in cardiac
      volume, ejection fraction, and infarct segment length between baseline and 20
      months after MI. Baseline echocardiographic measures were powerfully and
      independently predictive of all major outcomes.

PMID- 15967847
TI  - Defective regulation of interdomain interactions within the ryanodine receptor
      plays a key role in the pathogenesis of heart failure.
AB  - BACKGROUND: According to our hypothesis, 2 domains within the ryanodine receptor
      (RyR) of sarcoplasmic reticulum (SR) (N-terminal [0 to 600] and central [2000 to
      2500] domains), where many mutations have been found in patients with polymorphic
      ventricular tachycardia, interact with each other as a regulatory switch for
      channel gating. Here, we investigated whether the defective FKBP12.6-mediated
      stabilization of RyR in heart failure is produced by an abnormal interdomain
      interaction. METHODS AND RESULTS: SR vesicles were isolated from dog left
      ventricular muscles, and then the RyR moiety of the SR was fluorescently labeled
      with methylcoumarin acetate (MCA) using DPc10, a synthetic peptide corresponding
      to Gly2460-Pro2495 of RyR (one of the mutable domains in polymorphic ventricular
      tachycardia), as a site-directing carrier; the carrier was removed from the RyR
      after MCA labeling. Addition of DPc10 induced an unzipped state of the
      interacting N-terminal and central domains, as evidenced by an increase in the
      accessibility of the RyR-bound MCA fluorescence to a large fluorescence quencher.
      Domain unzipping resulted in Ca2+ leak through the RyR and facilitated cAMP
      dependent hyperphosphorylation of RyR and FKBP12.6 dissociation from RyR. When
      DPc10 was introduced into the isolated myocytes, the magnitude of intracellular
      Ca2+ transient decreased, and its decay time was prolonged. In the SR isolated
      from pacing-induced dog failing hearts, the domain unzipping has already
      occurred, together with FKBP12.6 dissociation and Ca2+ leak. CONCLUSIONS: The
      specific domain interaction within the RyR regulates the channel gating property,
      and the defectiveness in the mode of the interdomain interaction seems to be the
      initial critical step of the pathogenesis of heart failure.

PMID- 15967848
TI  - Improved myocardial beta-adrenergic responsiveness and signaling with exercise
      training in hypertension.
AB  - BACKGROUND: Cardiac responses to beta-adrenergic receptor stimulation are
      depressed with pressure overload-induced cardiac hypertrophy. We investigated
      whether exercise training could modify beta-adrenergic receptor responsiveness in
      a model of spontaneous hypertension by modifying the beta-adrenergic receptor
      desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+
      cycling proteins. METHODS AND RESULTS: Female spontaneously hypertensive rats
      (SHR; age, 4 months) were placed into a treadmill running (SHR-TRD; 20 m/min, 1
      h/d, 5 d/wk, 12 weeks) or sedentary group (SHR-SED). Age-matched Wistar Kyoto
      (WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY
      (P<0.01) and unaltered with exercise. Left ventricular (LV) diastolic anterior
      and posterior wall thicknesses were greater in SHR than WKY (P<0.001) and
      augmented with training (P<0.01). Langendorff LV performance was examined during
      isoproterenol (ISO) infusions (1x10(-10) to 1x10(-7) mol/L) and pacing stress
      (8.5 Hz). The peak LV developed pressure/ISO dose response was shifted rightward
      100-fold in SHR relative to WKY. The peak ISO LV developed pressure response was
      similar between WKY and SHR-SED and increased in SHR-TRD (P<0.05). SHR-TRD showed
      the greatest lusitropic response to ISO (P<0.05) and offset the pacing-induced
      increase in LV end-diastolic pressure and the time constant of isovolumic
      relaxation (tau) observed in WKY and SHR-SED. Improved cardiac responses to ISO
      in SHR-TRD were associated with normalized myocardial levels of GRK2 (P<0.05).
      SHR displayed increased L-type Ca2+ channel and sodium calcium exchanger
      abundance compared with WKY (P<0.001). Training increased ryanodine receptor
      phosphorylation and phospholamban phosphorylation at both the Ser16 and Thr17
      residues (P<0.05). CONCLUSIONS: Exercise training in hypertension improves the
      inotropic and lusitropic responsiveness to beta-adrenergic receptor stimulation
      despite augmenting LV wall thickness. A lower GRK2 abundance and an increased
      phosphorylation of key Ca2+ cycling proteins may be responsible for the above
      putative effects.

PMID- 15967849
TI  - Pharmacogenetic association of the angiotensin-converting enzyme
      insertion/deletion polymorphism on blood pressure and cardiovascular risk in
      relation to antihypertensive treatment: the Genetics of Hypertension-Associated
      Treatment (GenHAT) study.
AB  - BACKGROUND: Previous studies have reported that blood pressure response to
      antihypertensive medications is influenced by genetic variation in the renin
      angiotensin-aldosterone system, but no clinical trails have tested whether the
      ACE insertion/deletion (I/D) polymorphism modifies the association between the
      type of medication and multiple cardiovascular and renal phenotypes. METHODS AND
      RESULTS: We used a double-blind, active-controlled randomized trial of
      antihypertensive treatment that included hypertensives > or =55 years of age with
      > or =1 risk factor for cardiovascular disease. ACE I/D genotypes were determined
      in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or
      doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included
      fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction.
      Secondary outcomes included stroke, all-cause mortality, combined CHD, and
      combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096
      individuals during follow-up. The hazard rates for fatal and nonfatal CHD and the
      secondary outcomes were similar across antihypertensive treatments. ACE I/D
      genotype group was not associated with fatal and nonfatal CHD (relative risk of
      DD versus ID and II, 0.99; 95% CI, 0.91 to 1.07) or any secondary outcome. The 6
      year hazard rate for fatal and nonfatal CHD in the DD genotype group was not
      statistically different from the ID and II genotype group by type of treatment.
      No secondary outcome measure was statistically different across antihypertensive
      treatment and ACE I/D genotype strata. CONCLUSIONS: ACE I/D genotype group was
      not a predictor of CHD, nor did it modify the response to antihypertensive
      treatment. We conclude that the ACE I/D polymorphism is not a useful marker to
      predict antihypertensive treatment response.

PMID- 15967850
TI  - Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts
      cardiovascular events in well-functioning older adults.
AB  - BACKGROUND: Aging results in vascular stiffening and an increase in the velocity
      of the pressure wave as it travels down the aorta. Increased aortic pulse wave
      velocity (aPWV) has been associated with mortality in clinical but not general
      populations. The objective of this investigation was to determine whether aPWV is
      associated with total and cardiovascular (CV) mortality and CV events in a
      community-dwelling sample of older adults. METHODS AND RESULTS: aPWV was measured
      at baseline in 2488 participants from the Health, Aging and Body Composition
      (Health ABC) study. Vital status, cause of death and coronary heart disease
      (CHD), stroke, and congestive heart failure were determined from medical records.
      Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes.
      There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart
      failure. Results are presented by quartiles because of a threshold effect between
      the first and second aPWV quartiles. Higher aPWV was associated with both total
      mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus
      1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for
      quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly
      associated with CHD (P=0.007) and stroke (P=0.001). These associations remained
      after adjustment for age, gender, race, systolic blood pressure, known CV
      disease, and other variables related to events. CONCLUSIONS: Among generally
      healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness,
      is associated with higher CV mortality, CHD, and stroke.

PMID- 15967852
TI  - Is obesity a risk factor for mortality in coronary artery bypass surgery?
AB  - BACKGROUND: The published articles examining obesity and CABG surgery contain
      conflicting results about the role of body mass index (BMI) as a risk factor for
      in-hospital mortality. METHODS AND RESULTS: We studied 16 218 patients who
      underwent isolated CABG in the Providence Health System Cardiovascular Study
      Group database from 1997 to 2003. The effect of BMI on in-hospital mortality was
      assessed by logistic regression, with BMI group (underweight, normal, overweight,
      and 3 subgroups of obesity) as a categorical variable or transformations,
      including fractional polynomials, of BMI as a continuous variable. BMI was not a
      statistically significant risk factor for mortality in any of these assessments.
      However, using cumulative sum techniques, we found that the lowest risk-adjusted
      CABG in-hospital mortality was in the high-normal and that overweight BMI
      subgroup patients with lower or higher BMI had slightly increased mortality.
      CONCLUSIONS: Body size is not a significant risk factor for CABG mortality, but
      the lowest mortality is found in the high-normal and overweight subgroups
      compared with obese and underweight.

PMID- 15967851
TI  - Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine
      P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results
      of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI
      26 trial.
AB  - BACKGROUND: Despite the current standard antiplatelet regimen of aspirin and
      clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous
      coronary intervention patients, periprocedural and postprocedural ischemic events
      continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine
      P2Y(12) receptor antagonist, has the potential to achieve higher levels of
      inhibition of ADP-induced platelet aggregation than currently approved doses of
      clopidogrel. METHODS AND RESULTS: Joint Utilization of Medications to Block
      Platelets Optimally-Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was
      a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel
      versus clopidogrel in 904 patients undergoing elective or urgent percutaneous
      coronary intervention. Patients were randomized to either standard dosing with
      clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for
      bleeding and clinical events. The primary end point of the trial was clinically
      significant (TIMI major plus minor) non-CABG-related bleeding events in prasugrel
      versus clopidogrel-treated patients. Hemorrhagic complications were infrequent,
      with no significant difference between patients treated with prasugrel or
      clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio,
      1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically
      lower incidences of the primary efficacy composite end point (30-day major
      adverse cardiac events) and of the secondary end points myocardial infarction,
      recurrent ischemia, and clinical target vessel thrombosis. CONCLUSIONS: In this
      phase 2 study, which was designed to assess safety when administered at the time
      of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in
      low rates of bleeding. The results of this trial serve as a foundation for the
      large phase 3 clinical trial designed to assess both efficacy and safety.

PMID- 15967853
TI  - Symptoms other than chest pain may be important in the diagnosis of "silent
      ischemia," or "the sounds of silence".

PMID- 15967854
TI  - Images in cardiovascular medicine. Free-floating thrombus in right heart and
      massive pulmonary embolism migrating into pulmonary artery.

PMID- 15967855
TI  - Images in cardiovascular medicine. Giant coronary artery aneurysms in Kawasaki
      disease.

PMID- 15967856
TI  - Images in cardiovascular medicine. Anomalous coronary anatomy.

PMID- 15967857
TI  - Letter regarding article by Argaud et al, "postconditioning inhibits
      mitochondrial permeability transition".

PMID- 15967858
TI  - Is prosthesis-patient mismatch a clinically relevant entity?

PMID- 15967859
TI  - Molecular images of neovascularization: art for art's sake or form with a
      function?

PMID- 15967860
TI  - Echocardiography as a noninvasive Swan-Ganz catheter.

PMID- 15967861
TI  - Renoprotective action of fenoldopam in high-risk patients undergoing cardiac
      surgery: a prospective, double-blind, randomized clinical trial.
AB  - BACKGROUND: Acute renal failure is a serious complication of cardiac surgery
      causing high morbidity and mortality. The aim of this study was to evaluate the
      usefulness of fenoldopam, a specific agonist of the dopamine-1 receptor, in
      patients at high risk of perioperative renal dysfunction. METHODS AND RESULTS: A
      prospective single-center, randomized, double-blind trial was performed after
      local ethical committee approval and after written consent was obtained from 80
      patients undergoing cardiac surgery. Patients received either fenoldopam at 0.05
      microg/kg per minute or dopamine at 2.5 microg/kg per minute after the induction
      of anesthesia for a 24-hour period. All these patients were at high risk of
      perioperative renal dysfunction as indicated by Continuous Improvement in Cardiac
      Surgery Program score >10. Primary end point was defined as 25% creatinine
      increase from baseline levels after cardiac surgery. The 2 groups (fenoldopam
      versus dopamine) were homogeneous cohorts, and no difference in outcome was
      observed. Acute renal failure was similar: 17 of 40 (42.5%) in the fenoldopam
      group and 16 of 40 (40%) in the dopamine group (P=0.9). Peak postoperative serum
      creatinine level, intensive care unit and hospital stay, and mortality were also
      similar in the 2 groups. CONCLUSIONS: Despite an increasing number of reports of
      renal protective properties from fenoldopam, we observed no difference in the
      clinical outcome compared with dopamine in a high-risk population undergoing
      cardiac surgery.

PMID- 15967862
TI  - Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and
      treatment strategies.

PMID- 15967863
TI  - Heart failure devices: implantable cardioverter-defibrillators and biventricular
      pacing therapy.

PMID- 15967864
TI  - Lay rescuer automated external defibrillator ("public access defibrillation")
      programs: lessons learned from an international multicenter trial: advisory
      statement from the American Heart Association Emergency Cardiovascular Committee;
      the Council on Cardiopulmonary, Perioperative, and Critical Care; and the Council
      on Clinical Cardiology.
AB  - Lay rescuer automated external defibrillator (AED) programs may increase the
      number of people experiencing sudden cardiac arrest who receive bystander
      cardiopulmonary resuscitation (CPR), can reduce time to defibrillation, and may
      improve survival from sudden cardiac arrest. These programs require an organized
      and practiced response, with rescuers trained and equipped to recognize
      emergencies, activate the emergency medical services system, provide CPR, and
      provide defibrillation. To determine the effect of public access defibrillation
      (PAD) programs on survival and other outcomes after SCA, the National Heart,
      Lung, and Blood Institute, the American Heart Association (AHA), and others
      funded a large prospective randomized trial. The results of this study were
      recently published in The New England Journal of Medicine and support current AHA
      recommendations for lay rescuer AED programs and emphasis on planning, training,
      and practice of CPR and use of AEDs. The purpose of this statement is to
      highlight important findings of the Public Access Defibrillation Trial and
      summarize implications of these findings for healthcare providers, healthcare
      policy advocates, and the AHA training network.

PMID- 15967865
TI  - More evidence of cardiorenal protective effects of peroxisome proliferator
      activated receptor activation.

PMID- 15967867
TI  - "Idiopathic" instead of "essential" or "primary" hypertension?

PMID- 15967866
TI  - Peroxisome proliferator-activated receptor-alpha activation reduces salt
      dependent hypertension during chronic endothelin B receptor blockade.
AB  - Endothelin B (ETB) receptor stimulation inhibits sodium transport in a similar
      fashion as 20-HETE. Clofibrate, a peroxisome proliferator-activated receptor
      alpha (PPAR-alpha) agonist, increases protein expression of cytochrome P450 4A
      (CYP4A), which is responsible for 20-HETE synthesis in the kidney. Experiments
      were designed to determine whether clofibrate reduces hypertension associated
      with chronic ETB receptor blockade. Male Sprague-Dawley rats received either
      normal-salt (0.8% NaCl) or high-salt (8% NaCl) diet for 10 days. Female rats were
      fed a high-salt (8% NaCl) diet for 10 days. During the last 7 days, rats of both
      sexes were divided into 3 treatment groups: (1) clofibrate in drinking water (80
      mg per day), (2) ETB receptor antagonist A-192621 in food (10 mg/kg per day), or
      (3) clofibrate and A-192621. During ETB receptor blockade, clofibrate had no
      effect on mean arterial pressure (MAP) under normal salt conditions. In contrast,
      clofibrate significantly inhibited the increase in MAP produced by A-192621 in
      rats fed a high-salt diet (34+/-3 versus 19+/-4 mm Hg; P <0.05). Similar results
      were observed in female rats administered A-192621 and fed a high-salt diet. ETB
      receptor blockade significantly decreased CYP4A protein expression in the renal
      cortex of rats on high salt. Clofibrate significantly increased renal cortical
      and medullary CYP4A protein expression in A-192621-treated male rats on high
      salt. Therefore, chronic PPAR-alpha agonist treatment reduces salt-dependent
      hypertension produced by ETB receptor blockade in male and female Sprague-Dawley
      rats. This suggests a possible relationship between ETB receptor activation and
      the maintenance of CYP4A protein expression in the kidney of rats fed a high-salt
      diet.

PMID- 15967868
TI  - Tyramine-induced vasodilation mediated by dopamine contamination: a paradox
      resolved.
AB  - We reported previously that intravenous administration of tyramine induced a
      paradoxical forearm vasodilation and an increase in plasma dopamine, raising the
      possibility that dopamine is released by or converted from tyramine in vivo.
      Alternatively, tyramine can be nonenzymatically oxidized into dopamine in vitro,
      and this contamination may be responsible for the increase in plasma dopamine and
      forearm vasodilation. To distinguish between these possibilities, we measured the
      hemodynamic and neurohumoral effects of an intravenous infusion of a specially
      prepared dopamine-free tyramine solution in 8 normal volunteers at a dose that
      increased systolic blood pressure by approximately 25 mm Hg (from 107+/-5 to
      133+/-5 mm Hg; P <0.001) and compared it with an equivalent dose of
      norepinephrine. Tyramine increased plasma norepinephrine (139+/-18 to 226+/-30
      pg/mL; P <0.02), its intraneuronal metabolite dihydroxyphenylglycol (980+/-73 to
      2245+/-206 pg/mL; P <0.001), and systemic vascular resistance, but not plasma
      dopamine or its intraneuronal metabolite dihydroxyphenylacetic acid. Tyramine and
      norepinephrine produced nonsignificant increases in forearm vascular resistance.
      We conclude that tyramine-induced forearm vasodilation reported in previous
      studies is explained by the presence of dopamine contamination in tyramine
      preparations. Intravenous administration of dopamine-free tyramine and
      norepinephrine produced equivalent systemic vasoconstriction. The forearm
      vasculature was not useful in monitoring the vasoconstrictive effects of either
      agent. The possibility of dopamine contamination needs to be considered when
      interpreting previously published studies using tyramine as a pharmacological
      tool to assess sympathetic function, and it must be avoided in future studies.

PMID- 15967869
TI  - Relaxin reverses cardiac and renal fibrosis in spontaneously hypertensive rats.
AB  - The antifibrotic effects of the peptide hormone relaxin on cardiac and renal
      fibrosis were studied in 9- to 10-month-old male spontaneously hypertensive rats
      (SHR) and normotensive Wistar-Kyoto rats (WKY). Rats (n=8 to 9 per group) were
      allocated into 3 groups: WKY controls, vehicle-treated SHR (SHR-V), and relaxin
      treated SHR (SHR-R). Relaxin (0.5 mg/kg per day) was administered via
      subcutaneously implanted osmotic mini-pumps over 2 weeks before hearts and
      kidneys were harvested for analysis. Collagen content was analyzed by
      hydroxyproline assay, gel electrophoresis, and quantitative histology. Zymography
      was used to determine matrix metalloproteinase (MMP) expression and Western
      blotting to determine proliferating cell nuclear antigen (PCNA) expression and
      alpha-smooth muscle actin (alpha-SMA)/myofibroblast expression, whereas cardiac
      hypertrophy was assessed by myocyte size and real-time polymerase chain reaction
      of associated genes. The left ventricular (LV) myocardium of SHR-V contained
      increased collagen levels (by 25+/-1%, P<0.01 using biochemical analysis and 3
      fold; P<0.01 using quantitative histology), enhanced expression of PCNA (by 70+/
      8%; P<0.01), alpha-SMA (by 32+/-2%; P<0.05), and the collagen-degrading enzyme
      MMP-9 (by 70+/-6%; P<0.05) versus respective levels measured in WKY controls. The
      kidneys of SHR-V also contained increased collagen (25+/-2%, P<0.05 using
      biochemical analysis and 2.4-fold; P<0.01 using quantitative histology). Relaxin
      treatment significantly normalized collagen content in the LV (P<0.01) and kidney
      (P<0.05), completely inhibited cell proliferation (P<0.01) and fibroblast
      differentiation (P<0.05) in the LV, and increased MMP-2 expression (by 25+/-1%;
      P<0.05) without affecting MMP-9 in the LV compared with that measured in SHR-V.
      Thus, relaxin is a potent antifibrotic hormone with a rapid-occurring efficacy
      that may have therapeutic potential for hypertensive disease.

PMID- 15967870
TI  - Pioglitazone improves aortic wall elasticity in a rat model of elastocalcinotic
      arteriosclerosis.
AB  - Specific treatment of age-related aortic wall arteriosclerosis and stiffening is
      lacking. Because ligands for peroxisome proliferator-activated receptor gamma
      have beneficial effects on the arterial wall in atherosclerosis, via an
      antiinflammatory mechanism, we investigated whether long-term pioglitazone (Pio)
      treatment protects against another form of vascular wall disease,
      arteriosclerosis. We evaluated, in a rat model of elastocalcinotic
      arteriosclerosis (hypervitaminosis D and nicotine [VDN]), whether Pio (3 mg . kg(
      1) per day for 1.5 month PO) attenuated arteriosclerosis and its consequences:
      aortic wall rigidity, increased aortic pulse pressure, and left ventricular
      hypertrophy. In VDN rats, medial calcification was associated with
      monocyte/macrophage infiltration and induction of tumor necrosis factor alpha and
      interleukin 1beta. Pio increased nuclear peroxisome proliferator-activated
      receptor gamma immunostaining in the aortic wall, decreased tumor necrosis factor
      alpha (P <0.05 versus VDN Pio-), tended to decrease interleukin 1beta mRNA
      expression (P =0.08 versus VDN Pio-), blunted aortic wall calcification (271+/
      69, P <0.05 versus VDN Pio- 562+/-87 micromol . g(-1) dry weight) and prevented
      fragmentation of elastic fibers (segments per 10,000 microm2: 8.4+/-0.3; P <0.05
      versus VDN Pio- 10.5+/-0.6). Pio reduced aortic wall stiffness (elastic
      modulus/wall stress: 4.8+/-0.6; P <0.05 versus VDN Pio- 10.0+/-1.6), aortic pulse
      pressure (30+/-2 mm Hg; P <0.05 versus VDN Pio- 39+/-4) and left ventricular
      hypertrophy (1.58+/-0.05 g . kg(-1); P <0.05 versus VDN Pio- 1.76+/-0.06). In
      conclusion, long-term Pio treatment attenuates aortic wall elastocalcinosis and,
      thus, lowers aortic wall stiffness, aortic pulse pressure, and left ventricular
      hypertrophy.

PMID- 15967871
TI  - Long renal arteries: too much of a good thing?

PMID- 15967872
TI  - Renin-dependent hypertension caused by nonfocal stenotic aberrant renal arteries:
      proof of a new syndrome.
AB  - We have identified 2 relatively young patients with significant hypertension, an
      elongated single aberrant renal artery supplying blood to a renal segment, and
      evidence for localization of the elevated plasma renin activity to the side and
      vein draining the affected kidney. Furosemide-induced diuresis and acute oral
      captopril stimulated the renal vein/contralateral renin ratios to 4.3:1 and 6.5:1
      in patients 1 and 2, respectively. These renal vein ratios are significantly
      higher than normal (>3:1 under similar conditions). Partial resection of the
      portion of the kidney affected by the aberrant tortuous artery led to a marked
      reduction in blood pressure in patient 1. Patient 2, not an operative candidate,
      responded satisfactorily to use of a converting enzyme inhibitor, which helped to
      confirm the dependency of the blood pressure on the abnormal flow relationship
      existing within that aberrant artery and the kidney. We believe these 2 patients
      are representative of a small but distinct subgroup within the larger number of
      patients with elongated single or multiple renal aberrant arteries. Each aberrant
      artery had no focal stenosis, although a decrease in flow relative to the tissue
      perfusion demands was apparent from the marked activation of the renin
      angiotensin system in the venous system draining that artery. The increased
      length of such vessels may contribute to their decreased flow, although their
      average diameter may reside just above such a critical value for a normal length
      vessel. This new syndrome, involving more than one component of the
      flow/resistance relationship, has been overlooked when renin-dependent forms of
      hypertension are considered.

PMID- 15967873
TI  - Functional complementation and the analysis of opioid receptor homodimerization.
AB  - Complementation of function after coexpression of pairs of nonfunctional G
      protein-coupled receptors that contain distinct inactivating mutations supports
      the hypothesis that such receptors exist as dimers. Chimeras between members of
      the metabotropic glutamate receptor-like family have been particularly useful
      because the N-terminal ligand binding and heptahelical transmembrane elements can
      be considered distinct domains. To examine the utility of a related approach for
      opioid receptors, fusion proteins were generated in which a pertussis toxin
      resistant (Cys351Ile) variant of the G protein Gi1alpha was linked to the C
      terminal tails of the delta opioid peptide (DOP), kappa opioid peptide, and mu
      opioid peptide receptors. Each was functional as measured by agonist stimulation
      of guanosine 5'-([gamma-35S]thio)triphosphate ([35S]GTPgammaS) binding in Gialpha
      immunoprecipitates from membranes of pertussis toxin-treated HEK293 cells.
      Agonist function was eliminated either by fusion of the receptors to
      Gi1alphaGly202Ala,Cys351Ile or mutation of a pair of conserved Val residues in
      intracellular loop 2 of each receptor. Coexpression, but not simple mixing, of
      the two inactive fusion proteins reconstituted agonist-loading of [35S]GTPgammaS
      for each receptor. At equimolar amounts, reconstitution of DOP receptor function
      was more extensive than kappa or mu opioid receptor. Reconstitution of DOP
      function required two intact receptors and was not achieved by provision of extra
      Gi1alphaCys351Ile membrane anchored by linkage to DOP transmembrane domain 1.
      Inactive forms of all G protein alpha subunits can be produced by mutations
      equivalent to Gi1alphaGly202Ala. Because the amino acids modified in the opioid
      receptors are highly conserved in most rhodopsin-like receptors, this approach
      should be widely applicable to study the existence and molecular basis of
      receptor dimerization.

PMID- 15967874
TI  - Capsaicin regulates voltage-dependent sodium channels by altering lipid bilayer
      elasticity.
AB  - At submicromolar concentrations, capsaicin specifically activates the TRPV1
      receptor involved in nociception. At micro- to millimolar concentrations,
      commonly used in clinical and in vitro studies, capsaicin also modulates the
      function of a large number of seemingly unrelated membrane proteins, many of
      which are similarly modulated by the capsaicin antagonist capsazepine. The
      mechanism(s) underlying this widespread regulation of protein function are not
      understood. We investigated whether capsaicin could regulate membrane protein
      function by changing the elasticity of the host lipid bilayer. This was done by
      studying capsaicin's effects on lipid bilayer stiffness, measured using
      gramicidin A (gA) channels as molecular force-transducers, and on voltage
      dependent sodium channels (VDSC) known to be regulated by bilayer elasticity.
      Capsaicin and capsazepine (10-100 microM) increase gA channel appearance rate and
      lifetime without measurably altering bilayer thickness or channel conductance,
      meaning that the changes in bilayer elasticity are sufficient to alter the
      conformation of an embedded protein. Capsaicin and capsazepine promote VDSC
      inactivation, similar to other amphiphiles that decrease bilayer stiffness,
      producing use-dependent current inhibition. For capsaicin, the quantitative
      relation between the decrease in bilayer stiffness and the hyperpolarizing shift
      in inactivation conforms to that previously found for other amphiphiles.
      Capsaicin's effects on gA channels and VDSC are similar to those of Triton X-100,
      although these amphiphiles promote opposite lipid monolayer curvature. We
      conclude that capsaicin can regulate VDSC function by altering bilayer
      elasticity. This mechanism may underlie the promiscuous regulation of membrane
      protein function by capsaicin and capsazepine-and by amphiphilic drugs generally.

PMID- 15967875
TI  - Thromboxane A2 promotes interleukin-6 biosynthesis mediated by an activation of
      cyclic AMP-response element-binding protein in 1321N1 human astrocytoma cells.
AB  - 1321N1 human astrocytoma cells express thromboxane A2 (TXA2) receptors (TP).
      However, physiological consequences of TXA2 signaling in glial cells remain
      unclear. Herein, we show that TXA2 promotes interleukin-6 (IL-6) biosynthesis in
      glial cells. A TP agonist, 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prosta-5Z,13E
      dien-1-oic acid (U46619), enhanced IL-6 production in both 1321N1 cells and
      cultured mouse astrocytes. It has been shown that IL-6 gene expression is
      regulated by various transcription factors. Among them, we found a significant
      increase in cyclic AMP-response element-binding protein (CREB) activity with its
      phosphorylation at Ser133 by U46619 in 1321N1 cells. Although U46619 increased IL
      6 promoter activity, a mutation at cyclic AMP-response element (CRE) on the
      promoter clearly suppressed the effect, suggesting that CRE is involved in U46619
      induced IL-6 expression. Furthermore, both CREB and IL-6 promoter activities were
      suppressed by SB203580 [4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4
      pyridyl)-1H-imidazole], a p38 mitogen-activated protein kinase (MAPK) inhibitor,
      and H89 [N-[2-(4-bromocinnamylamino)-ethyl]-5-isoquinoline], a protein kinase A
      (PKA) inhibitor, indicating involvements of p38 MAPK and PKA in CREB activation
      and IL-6 expression. To determine which G-proteins are implicated in the U46619
      induced IL-6 synthesis, the interfering mutants of Galpha(q), Galpha12, or
      Galpha13 by were overexpressed in 1321N1 cells adenoviral approach. It is
      noteworthy that the Galpha(q) or Galpha13 mutant blocked the IL-6 production by
      U46619. The constitutively active mutant of Galpha(q), Galpha12, or Galpha13
      enhanced IL-6 production, indicating that Galpha(q) and Galpha13 were involved in
      U46619-induced IL-6 production. In conclusion, TXA2 enhances the IL-6
      biosynthesis via the PKA p38 MAPK/CREB pathway in 1321N1 cells. IL-6 induction
      depends on Galpha(q) and Galpha13 as well. This is the first report showing TP
      mediated IL-6 production in glial cells.

PMID- 15967876
TI  - Intracellular K+ is required for the inactivation-induced high-affinity binding
      of cisapride to HERG channels.
AB  - Many commonly used medications can cause long QT syndrome and thus increase the
      risk of life-threatening arrhythmias. High-affinity human Ether-a-go-go-related
      gene (HERG) potassium channel blockade by structurally diverse compounds is
      almost exclusively responsible for this side effect. Understanding drug-HERG
      channel interactions is an important step in avoiding drug-induced long QT
      syndromes. Previous studies have found that disrupting HERG inactivation reduces
      the degree of drug block and have suggested that the inactivated state is the
      preferential state for drug binding to HERG channels. However, recent studies
      have also shown that inactivation does not dictate drug sensitivity of HERG
      channels. In the present study, we examined the effect of inactivation gating on
      cisapride block of HERG. Modulation of HERG inactivation was achieved by either
      changing extracellular K+ or Cs+ concentrations or by mutations of the channel.
      We found that although inactivation facilitated cisapride block of the HERG K+
      current, it was not coupled with cisapride block of HERG when the Cs+ current was
      recorded. Furthermore, cisapride block of the HERG K+ current was not linked with
      inactivation in the mutant HERG channels F656V and F656M. Our results suggest
      that inactivation facilitates cisapride block of HERG channels through affecting
      the positioning of Phe-656.

PMID- 15967878
TI  - Clinical trial registration: a statement from the International Committee of
      Medical Journal Editors.

PMID- 15967877
TI  - Redox regulation of PTEN by S-nitrosothiols.
AB  - PTEN (phosphatase with sequence homology to tensin) is a phosphatidylinositol
      3,4,5-trisphosphate phosphatase that regulates many cellular processes. Activity
      of the enzyme is dependent on the redox state of the active site cysteine such
      that oxidation by H2O2 leads to inhibition. Because S-nitrosothiols are known to
      modify enzymes containing reactive cysteines, we hypothesized that S
      nitrosothiols would oxidize PTEN and inhibit its phosphatase activity. In the
      present study, we show that S-nitrosocysteine (CSNO), S-nitrosoglutathione
      (GSNO), and S-nitroso-N-acetylpenicillamine (SNAP) reversibly oxidized
      recombinant PTEN. In addition, CSNO led to concentration- and time-dependent
      oxidation of endogenous cellular PTEN. However, in contrast, GSNO and SNAP were
      effective only when coincubated with cysteine, suggesting that these
      nitrosothiols must react with cysteine to form CSNO, which can be transferred
      across cell membranes. Oxidation of cellular PTEN resulted from thiol
      modification and led to reversible inhibition of phosphatase activity. Although
      oxidation of PTEN by H2O2 led to formation of an intramolecular disulfide,
      oxidation of PTEN by CSNO seemed to lead to formation of a mixed disulfide.
      Glutathionylation of cellular proteins by incubating cells with diamide or
      incubating cellular extracts with GSSG oxidized PTEN in a manner similar to that
      of CSNO. Overall, these data demonstrate for the first time that S-nitrosothiols
      oxidatively modify PTEN, leading to reversible inhibition of its phosphatase
      activity, and suggest that the oxidized species is a mixed disulfide.

PMID- 15967879
TI  - GJB2 and GJB6 mutations: genotypic and phenotypic correlations in a large cohort
      of hearing-impaired patients.
AB  - OBJECTIVES: To analyze the clinical features of hearing impairment and to search
      for correlations with the genotype in patients with DFNB1. DESIGN: Case series.
      SETTING: Collaborative study in referral centers, institutional practice.
      Patients A total of 256 hearing-impaired patients selected on the basis of the
      presence of biallelic mutations in GJB2 or the association of 1 GJB2 mutation
      with the GJB6 deletion (GJB6-D13S1830)del. MAIN OUTCOME MEASURES: The prevalence
      of GJB2 mutations and the GJB6 deletion and audiometric phenotypes related to the
      most frequent genotypes. RESULTS: Twenty-nine different GJB2 mutations were
      identified. Allelic frequency of 35delG was 69%, and the other common mutations,
      313del14, E47X, Q57X, and L90P, accounted for 2.6% to 2.9% of the variants.
      Concerning GJB6, (GJB6-D13S1830)del accounted for 5% of all mutated alleles and
      was observed in 25 of 93 compound heterozygous patients. Three novel GJB2
      mutations, 355del9, V95M, and 573delCA, were identified. Hearing impairment was
      frequently less severe in compound heterozygotes 35delG/L90P and 35delG/N206S
      than in 35delG homozygotes. Moderate or mild hearing impairment was more frequent
      in patients with 1 or 2 noninactivating mutations than in patients with 2
      inactivating mutations. Of 93 patients, hearing loss was stable in 73,
      progressive in 21, and fluctuant in 2. Progressive hearing loss was more frequent
      in patients with 1 or 2 noninactivating mutations than in those with 2
      inactivating mutations. In 49 families, hearing loss was compared between
      siblings with similar genotypes, and variability in terms of severity was found
      in 18 families (37%). CONCLUSION: Genotype may affect deafness severity, but
      environmental and other genetic factors may also modulate the severity and
      evolution of GJB2-GJB6 deafness.

PMID- 15967880
TI  - Predicting basal cochlear length for electric-acoustic stimulation.
AB  - OBJECTIVE: To assess the feasibility and accuracy of predicting electrode
      insertion depth necessary in cochlear implantations for electric-acoustic
      stimulation by means of preoperative high-resolution computed tomography (HRCT).
      DESIGN: Human temporal bone study with evaluation of cochlear dimensions.
      SETTING: Tertiary care medical center. METHODS: Eight fresh human temporal bones
      were scanned, and basal cochlear structures were reconstructed and measured.
      Standard cochlear implantations with a free-fitting array were performed, and the
      bones then underwent histologic analysis using a technique that allows sectioning
      of undecalcified bones. After embedding, all bones underwent conventional
      radiologic analysis with further insertion measurements. Preimplantation HRCT
      data were compared with radiologic and histologic data. RESULTS: Preimplantation
      HRCT-based measurements correlated very well with postimplantation radiologic
      data. A mean failure of 0.3 mm was found. Mean values for the first 360 degrees
      ranged from 18.8 to 22.0 mm. CONCLUSIONS: Preimplantation HRCT-based prediction
      of cochlear implant insertion depths is both feasible and accurate. It is
      especially useful when aiming for hearing preservation, where insertion depths of
      360 degrees are necessary.

PMID- 15967881
TI  - Relationship of technetium Tc 99m sestamibi scans to histopathological features
      of hyperfunctioning parathyroid tissue.
AB  - OBJECTIVE: To investigate the histopathological features of pathologic
      parathyroid specimens associated with negative preoperative technetium Tc 99m
      sestamibi scans. DESIGN: Retrospective study. SETTING: Tertiary care center.
      PATIENTS: One hundred fourteen patients who underwent sestamibi scans before
      surgical exploration for primary hyperparathyroidism between 1996 and 2001.
      INTERVENTIONS: Surgical exploration and removal of parathyroid adenomas. MAIN
      OUTCOME MEASURES: Histopathological characteristics associated with true-positive
      and false-negative sestamibi scans, including parathyroid specimen weight, size,
      relative oxyphil and chief cell content, parathyroid hormone staining patterns,
      cellular architecture, and various immunohistochemical staining patterns.
      RESULTS: Twenty-three (24%) of 98 patients with parathyroid adenomas had negative
      sestamibi scan results. Among 20 age- and sex-matched patients with false
      negative results vs 20 patients with true-positive results, tumor size (P = .04)
      and oxyphil cell content (P = .03) were found to be significantly different.
      CONCLUSION: Parathyroid gland size and oxyphil content are descriptive and
      predict differences between sestamibi properties of parathyroid adenomas but have
      no current therapeutic implications for parathyroid surgery.

PMID- 15967882
TI  - Characterization of submucosal lesions using optical coherence tomography in the
      rabbit subglottis.
AB  - OBJECTIVE: To evaluate the efficacy of optical coherence tomography in
      differentiating between several simulated subglottic lesions, using an ex vivo
      rabbit laryngotracheal model. DESIGN: Laryngotracheal complexes were harvested
      from euthanized rabbits and divided into the following 4 groups: (1) control, (2)
      submucosal collagen injection (simulating scar formation), (3) dehydration and
      rehydration (simulating edema), and (4) repeated intubation trauma. The
      subglottic region was imaged using optical coherence tomography. Images were
      later correlated with conventional histologic findings. RESULTS: The epithelium,
      basement membrane, lamina propria, perichondrium, and cartilage (cricoid and
      tracheal) were clearly imaged. In group 2, an increase in the thickness of the
      lamina propria was observed, in addition to a characteristic optical pattern of
      the injected collagen. Dehydration (in group 3) produced a visible reduction in
      the thickness of the lamina propria, while rehydration of the same specimen with
      distilled water revealed a significant increase in submucosal swelling. Repeated
      intubation (in group 4) resulted in tissue edema that was seen as wavy
      heterogeneous thickening of the lamina propria. Edema produced by repeated
      intubation or distilled water immersion was easily differentiated from native and
      collagen-injected tissues. CONCLUSION: Optical coherence tomography successfully
      identifies the microstructure layers of the subglottis and can differentiate
      between edema and increased collagen deposition in the rabbit model.

PMID- 15967883
TI  - Cricotracheal resection in children weighing less than 10 kg.
AB  - OBJECTIVE: To review cricotracheal resection (CTR) in children weighing less than
      10 kg. DESIGN AND SETTING: Retrospective study of 17 patients (mean follow-up, 23
      months) from 3 ear, nose, and throat pediatric centers. PATIENTS: Seventeen
      children (10 boys and 7 girls; mean age, 14.6 months; and mean weight, 7.6 kg)
      undergoing CTR from June 1995 to March 2003. MAIN OUTCOME MEASURES: Decannulation
      rates and endoscopies. RESULTS: The cause was congenital subglottic stenosis in 2
      children (12%) and acquired subglottic stenosis in 15 (88%). All but 1 had grade
      3 or 4 stenosis. The mean hospitalization duration was 34 days. Single-stage CTR
      was performed in 11 children (65%), with peroperative decannulation in 7.
      Extubation of these patients occurred between days 3 and 9. Decannulation of the
      other 6 patients was performed after a median of 15 days. Sixteen (94%) of the 17
      children were decannulated. Four patients required additional carbon dioxide
      laser treatment for subsequent glottic or subglottic edema or granulomas, but no
      reintubation was necessary. One child could not be decannulated because of
      bronchopulmonary disease, and subglottic stenosis recurred. Long-term tracheotomy
      was avoided in all other patients. Another child died of cardiac disease. All
      other patients remained free of significant subglottic stenosis at follow-up.
      CONCLUSIONS: Cricotracheal resection in small children weighing less than 10 kg
      was a safe and effective procedure for severe subglottic stenosis. To our
      knowledge, this is the first reported attempt of CTR in this weight category,
      providing results comparable to those published in older children.

PMID- 15967884
TI  - Recovery of potential pathogens and interfering bacteria in the nasopharynx of
      otitis media-prone children and their smoking and nonsmoking parents.
AB  - OBJECTIVE: To study the frequency of isolation of potential pathogens and
      interfering bacteria in the posterior nasopharynx of otitis media-prone (OMP)
      children and their smoking and nonsmoking parents to possibly explain why active
      and passive exposure to smoking is associated with carriage of potentially
      pathogenic bacteria and an increased risk of respiratory tract infection in both
      adults and children. SETTING: Outpatient clinic. PARTICIPANTS: Twenty OMP
      children and their smoking parents (smoking group) and 20 OMP children and their
      nonsmoking parents (nonsmoking group). INTERVENTIONS: Posterior nasopharynx
      cultures were taken from 20 OMP children and their smoking parents and 20 OMP
      children and their nonsmoking parents. MAIN OUTCOME MEASURE: Potential pathogens
      and aerobic and anaerobic bacteria with interfering capabilities against these
      organisms were identified. RESULTS: Fourteen potential pathogens were isolated
      from smoking parents, and 17 were recovered from their children. Concordance in
      isolation of a pathogen between a parent and child was noted in 11 instances.
      Three potential pathogens were isolated from nonsmoking parents (P<.001 compared
      with the parents and children in the smoking group and children in the nonsmoking
      group), and 16 were recovered from their children. Bacterial interference by
      normal flora isolates against potential pathogens was noted in 58 instances in
      smoking parents and in 55 instances in their children (P<.05). Bacterial
      interference was noted in 129 instances in nonsmoking parents (P<.05 compared
      with the parents and children in the smoking group and children in the nonsmoking
      group) and in 55 instances in their children. CONCLUSIONS: A high recovery rate
      of potential pathogens and a low number of interfering organisms were observed in
      OMP children. This was not related to their parents' smoking habits. The
      posterior nasopharynx flora of smoking parents contained more potential pathogens
      similar to the ones recovered from OMP children and fewer interfering organisms
      than nonsmoking parents.

PMID- 15967885
TI  - Osseocutaneous radial forearm free tissue transfer for repair of complex
      midfacial defects.
AB  - OBJECTIVE: To evaluate the resulting aesthetics, function, and donor site
      morbidity of the osseocutaneous radial forearm free flap (OCRFFF) used for
      midface reconstruction. DESIGN: Prospective case series and a retrospective
      review of results. PATIENTS: Ten patients from an academic practice who underwent
      reconstruction at the University of Michigan Hospitals between 1995 and 2001.
      INTERVENTIONS: All patients had maxillectomy defects in which the entire
      infraorbital rim was reconstructed with an OCRFFF. Of the 10 patients included in
      the study, 3 underwent a total maxillectomy with orbital exenteration, 4 had a
      total maxillectomy without orbital exenteration, and 3 had a limited maxillectomy
      that did not involve the palate. Patients with palatal defects underwent
      reconstruction with a prosthetic palatal obturator. MAIN OUTCOME MEASURES: Facial
      contour and aesthetic results, speech understandability, ability to eat solid
      foods, oronasal separation, socializing outside the home, and return-to-work
      status. Flap success, donor site morbidity, and orbital complications were also
      studied. RESULTS: Mean +/- SEM follow-up was 23.2 +/- 5.0 months. A modified Funk
      facial deformity scale was used, and 7 of the 10 patients had either no deformity
      or minimal deformity. The mean aesthetic score for these reconstructions was 2.1
      +/- 0.3 on a scale of 1 to 4, with 1 representing no deformity and 4 representing
      a severe deformity. All patients returned to a solid diet and had understandable
      speech, although patients who had an orbital exenteration trended to poorer
      scores. All patients socialized either frequently or occasionally outside the
      home, and all patients not retired or disabled prior to surgery returned to work.
      CONCLUSION: The OCRFFF reconstruction of the infraorbital rim in patients with
      total maxillectomy defects and obturator of the palatal defect controls orbital
      complications and optimizes aesthetic outcome while achieving nearly normal
      palatal function.

PMID- 15967886
TI  - The relationship between frontal sinusitis and localization of the frontal sinus
      outflow tract: a computer-assisted anatomical and clinical study.
AB  - OBJECTIVE: To evaluate the relationship between frontal sinusitis and the
      localization of the frontal sinus outflow tract medial or lateral to the superior
      attachment of the uncinate process (UP). DESIGN: A retrospective anatomical and
      clinical study. SETTING: An ear, nose, and throat clinic in isli Etfal Teaching
      and Research Hospital, Istanbul, Turkey. PATIENTS: Paranasal sinus computed
      tomographic scans of 486 sides of the frontal sinuses (hereafter referred to as
      sides) of 243 patients who had chronic sinusitis were evaluated. In 125 sides
      (26%), the superior attachment of the UP could not be identified. In the
      remaining 361 sides (74%), the prevalence of superior attachment of UP types and
      the presence of frontal sinusitis in each side were recorded. Localization of the
      frontal sinus outflow tract was determined according to the superior attachment
      of the UP. Drainage of the frontal sinus to the middle meatus (medial to the
      superior attachment of the UP [types 1-3]) was classified as group 1, and
      drainage of the frontal sinus to the ethmoid infundibulum (lateral to the
      superior attachment of the UP [types 4-6]) was classified as group 2. RESULTS:
      Frontal sinusitis was found in 125 (35%) of 361 sides. The distribution of
      frontal sinusitis was 97 (41%) of 237 in group 1 and 28 (23%) of 124 in group 2.
      Group 1 drainage had a statistically significant presence of frontal sinusitis
      (chi(2) = 12.11; P<.001). The prevalence of superior attachment of UP types was
      63% for type 1/2, 3% for type 3, 12% for type 4, 14% for type 5, and 8% for type
      6. CONCLUSIONS: Frontal sinus outflow tract, which is medial to the superior
      attachment of the UP, is more common than the lateral one. There is a
      statistically significant relation between the presence of frontal sinusitis and
      the frontal sinus outflow tract, which is medial to the superior attachment of
      the UP.

PMID- 15967887
TI  - Pharyngeal perforation and pseudodiverticulum formation after anterior cervical
      spine plating.

PMID- 15967888
TI  - An unusual orbital foreign body resulting in the orbital apex syndrome: report of
      a case.

PMID- 15967889
TI  - Frontal sinus obliteration: an operation for the archives or modern
      armamentarium.

PMID- 15967890
TI  - Frontal sinus obliteration is rarely indicated.

PMID- 15967891
TI  - Growing obsolescence of the frontal sinus obliteration procedure.

PMID- 15967892
TI  - Radiology quiz case 1. Autoimmune inner ear disease (AIED).

PMID- 15967893
TI  - Radiology quiz case 2. Prestyloid parapharyngeal space pleomorphic adenoma.

PMID- 15967894
TI  - Addressing the long-term safety aspects of butterbur therapy: a call for
      immediate action.

PMID- 15967896
TI  - The difficulty of identifying and enumerating human errors.

PMID- 15967898
TI  - University of Texas Health Science Center at San Antonio.

PMID- 15967899
TI  - Pancreaticoduodenectomy is curative in the majority of patients with node
      negative ampullary cancer.
AB  - HYPOTHESIS: Survival following resection for ampullary carcinoma may be
      influenced by 1 or more clinical or pathologic variables. DESIGN: Retrospective
      medical records review. SETTING: Academic tertiary care center. PATIENTS: From
      July 1, 1991, through April 30, 2004, 72 patients (31 males and 41 females) were
      treated for ampullary carcinoma at Loyola University Medical Center, Maywood,
      Ill. Of these, 51 patients who underwent potentially curative
      pancreaticoduodenectomy were studied. INTERVENTIONS: Whipple procedure for
      attempted cure in 51 patients with ampullary adenocarcinoma. MAIN OUTCOME
      MEASURES: The effects of clinical and pathologic factors on disease-specific
      survival were analyzed using log-rank and a multivariate Cox proportional hazards
      model. RESULTS: The median age of the 51 patients (25 males and 26 females) was
      69 years (age range, 38-90 years). Median operative time was 6 hours (range, 4-12
      hours), and median estimated blood loss was 800 mL (range, 350-7500 mL). Thirty
      day mortality was 2% (1 of 51 patients). Twenty-seven had node-negative disease,
      34 cases were T1/T2, and 23 were well differentiated. Median follow-up for
      patients still alive was 42 months (range, 2-147 months); overall 5-year disease
      specific survival was 58%. Five-year survival was 78% (21/27) in node-negative
      patients, 73% (25/34) for T1/T2 patients, and 76% (17/23) for well-differentiated
      tumors compared with 25% for node-positive, 8% for T3/T4, and 36% for poorly or
      moderately differentiated tumors (P<.01). On multivariate analysis, only node
      negative disease maintained significance (hazard ratio, 5.2; 95% confidence
      interval, 1.2-21.9). In all groups, there were no deaths due to disease after 3
      years of survival was reached. CONCLUSION: Pancreaticoduodenectomy is curative in
      80% of patients with node-negative ampullary carcinomas. Once 3-year survival is
      reached, long-term survival can be expected.

PMID- 15967900
TI  - Ileal pouch-anal anastomosis: does age at the time of surgery affect outcome?
AB  - HYPOTHESIS: Functional outcome and quality of life in older patients (>55 years)
      undergoing ileal pouch-anal anastomosis (IPAA) for ulcerative colitis or familial
      adenomatous polyposis have been incompletely studied. Our aim was to update our
      understanding on how the age of the patient at the time of surgery influences
      functional outcome and quality of life after IPAA. METHODS: From January 1, 1981,
      to December 31, 2000, two thousand two patients who underwent IPAA were studied.
      Patients were grouped by age at operation: 45 years or younger (n = 1688),
      between 46 and 55 years (n = 249), and older than 55 years (n = 65). Mean age was
      33.5 years. Postoperative complications, function, and quality of life were
      assessed with a questionnaire administered annually. RESULTS: Follow-up for
      patients older than 55 years was a mean +/- SD of 8.1 +/- 4.8 years. Overall,
      follow-up was a mean of 10.1 +/- 5.7 years. The pouch failure rate for patients
      older than 55 years was 1.6% at 10 years. No statistically significant difference
      in pouch failure between age groups was observed. Overall, frequent daytime and
      nighttime incontinence, respectively, occurred in 5.6% and 13.3% of the patients
      at 10 years. Incontinence was more common in older patients (P = .002 at 3
      years). Quality of life as assessed by social activities, work, travel, sexual
      activity, family relationships, and sports and recreation was not significantly
      different among age groups. Most patients felt that their condition had improved
      or that they had no restrictions after IPAA. CONCLUSIONS: Postoperative
      complications after surgery seem to be unrelated to age at the time of surgery.
      Although incontinence may occur more frequently in older patients, IPAA does not
      adversely affect quality of life in patients older than 55 years.

PMID- 15967901
TI  - Gastrointestinal stromal tumors express ras oncogene: a potential role for
      diagnosis and treatment.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) constitute the largest
      category of nonepithelial neoplasms of the gastrointestinal tract.
      Histologically, they have a spindle cell appearance but stain by
      immunohistochemistry for the proto-oncogene, c-kit (CD117). There is some
      evidence that phosphorylation of these receptors leads to a cascade that may
      activate the ras/mitogen-activated protein kinase pathway, which may, in turn,
      allow other oncogenes to become active. HYPOTHESIS: Immunohistochemical staining
      pattern of GISTs will aid in their differentiation from other spindle cell tumors
      and predict clinical outcome in patients. DESIGN AND SETTING: Retrospective
      review of patient records and paraffin block specimens of spindle cell tumors.
      PATIENTS: We have identified 65 patients with spindle cell tumors of the
      gastrointestinal tract at our institution in the past 10 years. Tumors were
      diagnosed by their morphology as leiomyomas, leiomyoblastomas, or
      leiomyosarcomas. MAIN OUTCOME MEASURES: CD117 and ras p21 were stained by
      immunohistochemistry on formalin-fixed, paraffin-embedded sections of normal and
      tumor tissues. RESULTS: Of the 65 patients, there were 23 patients diagnosed as
      having GIST confirmed by CD117 expression and 42 patients without GIST.
      Gastrointestinal stromal tumor samples of 17 (77%) of 22 patients stained
      positive for ras protein compared with 0 of 27 patients with leiomyomas (P<.001).
      CONCLUSIONS: To our knowledge, this study is the first to demonstrate that GISTs
      stain positive for ras p21. This molecular trait may be a useful diagnostic tool
      in addition to the c-kit (CD117) to separate GISTs from leiomyomas and
      leiomyosarcomas. In the future, ras inhibitors may potentially be a therapeutic
      to treat GISTs.

PMID- 15967902
TI  - Short-term outcomes with small intestinal submucosa for ventral abdominal hernia.
AB  - HYPOTHESIS: A bioabsorbable tissue scaffold of porcine submucosal small intestine
      extracellular matrix (Surgisis Gold [SIS]; Cook Biotech Inc, West Lafayette, Ind)
      mesh is safe and effective for ventral hernia repair. DESIGN: Retrospective case
      series at a university teaching hospital. PATIENTS: Fifty-three consecutive
      patients having 8-ply SIS mesh repair of ventral abdominal hernias. MAIN OUTCOME
      MEASURES: Early complications, reoperation, hernia recurrence, mesh or wound
      infection, or reaction. Outcomes reported and compared on an intention-to-treat
      basis. RESULTS: Patients were stratified by wound class: clean, clean
      contaminated and contaminated, or dirty. Median follow-up was 14 months (range, 2
      29 months) during which there were 22 complications (41%), 17 early reoperations
      (32%), 13 partial dehiscences (21%), 6 mesh reactions (11%), and 9 recurrent
      hernias (17%). Seven recurrent hernias (78%) in critically ill, patients with
      dirty wounds had the SIS mesh removed owing to infection or reoperation. In
      patients without SIS mesh removal or debridement, 1 (2.2%) of 44 developed a
      recurrent hernia at 6 months. Patients with dirty wounds were more likely to need
      early reoperation (P<.001), develop a complication (P<.01), partial wound
      dehiscence (P<.05), or recurrent hernia (P<.01) compared with patients with clean
      wounds. Critically ill patients were more likely to have hernia recurrence
      (P<.05), early reoperation (P<.001), and postoperative complications (P<.05).
      CONCLUSIONS: Eight-ply SIS mesh is safe in clean and clean-contaminated hernia
      repair with satisfactory short-term outcomes. However, delayed wound infection,
      repeated operation, and mesh debridement warrant cautious use of SIS mesh in
      critically ill patients and those with dirty wounds.

PMID- 15967903
TI  - Failure of nonoperative management of splenic injuries: causes and consequences.
AB  - HYPOTHESIS: Presenting patient characteristics can predict which patients will
      fail nonoperative therapy of blunt splenic injuries. DESIGN: Retrospective
      descriptive population study. SETTING: All patients admitted with blunt splenic
      trauma were identified from a statewide trauma registry between January 1, 1995,
      and December 31, 2001. PATIENTS AND METHODS: Patients were characterized as
      requiring immediate intervention or successful or failed nonoperative management
      based on time from emergency department arrival to intervention (surgery or
      angioembolectomy). Injury and patient characteristics included age, the presence
      of hypotension, Injury Severity Score, and the Glasgow Coma Scale score. Risk
      factors for the failure of nonoperative management were evaluated using the
      chi(2) statistic. The failure of nonoperative management associated with the
      admitting hospital's trauma designation level was evaluated using logistic
      regression. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Determine factors
      associated with failure of nonoperative management of blunt splenic injuries.
      RESULTS: Two thousand two hundred forty-three patients met criteria for inclusion
      in the study. Six hundred ten patients (27%) underwent immediate splenectomy,
      splenorrhaphy, or splenic embolization (within 4 hours). Of the remaining 1633
      patients who were admitted with planned nonoperative management, 252 patients
      (15%) failed. Of the injury and patient characteristics reviewed, being older
      than 55 years and having an ISS higher than 25 were significantly associated with
      failure. Risk of failure also increased with admission to a level III or IV
      trauma hospital compared with a level I trauma hospital. CONCLUSIONS: Being older
      than 55 years and having an ISS higher than 25 along with admission to a level
      III or IV trauma hospital were associated with a significant risk of failure of
      nonoperative management of splenic injuries. The Glasgow Coma Scale score,
      associated injuries, and presenting hemodynamics were not predictive of failure
      in this large retrospective review.

PMID- 15967904
TI  - Comparison of the clinical and histological characteristics and survival of
      distal esophageal-gastroesophageal junction adenocarcinoma in patients with and
      without barrett mucosa.
AB  - BACKGROUND: The incidence of adenocarcinoma in the distal esophagus and at the
      gastroesophageal junction (GEJ) has been increasing in the last decades. It has
      been suggested that patients in whom Barrett mucosa can be identified in the
      surgical specimen have a better prognosis compared with those without. This has
      led to the belief that patients with and without Barrett mucosa may represent 2
      distinct cancer types. HYPOTHESIS: Distal esophageal-GEJ adenocarcinoma with and
      without Barrett mucosa share the same origin, but differ only in clinical
      presentation and outcome. DESIGN AND SETTING: Retrospective cohort study in a
      university tertiary referral center. PATIENTS AND METHODS: Between 1992 and 2002,
      215 patients (173 men and 42 women; median age, 66 years; age range, 26-91 years)
      had esophagogastrectomy for adenocarcinoma of the distal esophagus-GEJ. Patients
      receiving neoadjuvant chemotherapy or radiation therapy were excluded. MAIN
      OUTCOME MEASURES: Clinical presentation, tumor characteristics, and survival were
      compared in patients with Barrett mucosa (n = 140) and those without (n = 75).
      RESULTS: Patients with Barrett mucosa in the specimen had tumors that were
      diagnosed earlier; were smaller in size; earlier in stage, with fewer node
      metastases; and had a better 5-year survival. CONCLUSIONS: Observed differences
      in survival between patients with distal esophageal-GEJ adenocarcinoma with and
      without Barrett mucosa can be explained by earlier diagnosis. Patients without
      Barrett mucosa have their tumors detected later, when the disease is more
      advanced. This suggests the possibility that tumors without Barrett mucosa are
      not of a different origin, but rather are larger tumors that may have overgrown
      areas of Barrett mucosa.

PMID- 15967905
TI  - Hospitalization for acute diverticulitis does not mandate routine elective
      colectomy.
AB  - BACKGROUND: Previous studies suggest that elective colectomy is often required
      after an episode of acute diverticulitis. HYPOTHESIS: Acute diverticulitis
      initially treated nonoperatively does not require elective colectomy. DESIGN:
      Retrospective cohort study. SETTING: Twelve Kaiser Permanente hospitals in
      Southern California. PATIENTS: Three thousand one hundred sixty-five patients
      with acute diverticulitis. INTERVENTIONS: Colectomy or nonoperative treatment
      with or without percutaneous abscess drainage. MAIN OUTCOME MEASURES: Recurrent
      diverticulitis. RESULTS: Emergency colectomy was performed in 614 patients
      (19.4%). Nonoperative treatment was initially used in 2551 patients (80.6%). Of
      these, 185 patients (7.3%) had an elective colectomy and the remaining 2366
      patients (92.7%) did not. Factors associated with undergoing elective colectomy
      compared with nonoperative treatment were younger age of the patient, fewer
      comorbidities, and percutaneous abscess drainage. Mean follow-up was 8.9 years,
      with a maximum of 12 years. After nonoperative treatment, 314 patients (13.3%)
      recurred-222 patients had a single recurrence and 92 patients had a rerecurrence.
      After adjusting for other variables, older age (hazard ratio, >/=50 years vs <50
      years = 0.68; 95% confidence interval, 0.53-0.87) was associated with a lower
      recurrence, whereas higher comorbidity was associated with higher recurrence.
      Gender and percutaneous abscess drainage had no influence on recurrence. All 92
      rerecurrences were treated nonoperatively. The risk of a rerecurrence (29.3%) was
      significantly higher than a first recurrence (P<.001). Age, gender, Charlson
      comorbidity index, and percutaneous abscess drainage did not predict
      rerecurrence. CONCLUSIONS: Very few patients with acute diverticulitis treated
      nonoperatively have recurrence. Younger age was associated with recurrence. A
      first recurrence was the only factor that predicted rerecurrences. The low
      recurrence rate argues against routine elective colectomy after successful
      nonoperative management of acute diverticulitis.

PMID- 15967906
TI  - Feasibility of a randomized trial of extended lymphadenectomy for pancreatic
      cancer.
AB  - HYPOTHESIS: The required sample size of a prospective randomized trial comparing
      standard pancreaticoduodenectomy with pancreaticoduodenectomy plus extended
      lymphadenectomy for pancreatic adenocarcinoma is prohibitively large, making such
      a trial infeasible. DESIGN: Retrospective cohort study. SETTING: Comprehensive
      cancer center. PATIENTS: We identified 158 patients who underwent
      pancreaticoduodenectomy for pancreatic adenocarcinoma with separate pathologic
      analysis of second-echelon lymph nodes, defined as lymph nodes along the proximal
      hepatic artery and/or the great vessels. MAIN OUTCOME MEASURES: To estimate the
      sample size required for a randomized trial, we devised a biostatistical model
      with the following assumptions: extended lymphadenectomy can benefit only
      patients who (1) actually have disease removed from second-echelon nodes, (2)
      have microscopically negative (R0) primary tumor resection margins, and (3) do
      not have visceral metastatic (M0) disease. RESULTS: Seventy-six patients (48.1%)
      had negative first- and second-echelon lymph nodes, 65 (41.1%) had positive first
      echelon and negative second-echelon lymph nodes, and 17 (10.8%) had positive
      first- and second-echelon lymph nodes. Patients with positive second-echelon
      lymph nodes had an R0 resection rate of 47.1%. At a median follow-up of 65.1
      months, 4 patients with positive second-echelon lymph nodes were alive, but 3 had
      recurrent disease. This implies that only 1 patient (5.9%) with positive second
      echelon lymph nodes may have had true M0 disease. Therefore, only 0.3% of
      patients (10.8% with positive second-echelon lymph nodes x 47.1% with R0
      resection x 5.9% with M0 disease) may achieve a survival benefit from extended
      lymphadenectomy. A randomized trial of standard pancreaticoduodenectomy vs
      pancreaticoduodenectomy with extended lymphadenectomy would require 202 000
      patients in each study arm to detect such a small difference. CONCLUSIONS:
      Definitive evaluation of the potential benefits of extended lymphadenectomy would
      require a prohibitively large sample size. Adequately powered randomized trials
      to address the potential benefit of extended lymphadenectomy are infeasible.

PMID- 15967908
TI  - Effect of laparoscopic colon resection on postoperative glucose utilization and
      protein sparing: an integrated analysis of glucose and protein metabolism during
      the fasted and fed States using stable isotopes.
AB  - HYPOTHESIS: Using a stable isotope method to quantify postoperative changes in
      glucose and protein metabolism, patients undergoing laparoscopic-assisted colon
      resection and receiving 4 mg . kg(-1) . min(-1) of dextrose intravenously will
      (1) have more pronounced suppression of endogenous glucose production, leading to
      (2) a greater reduction in whole-body protein breakdown. DESIGN: Randomized
      protocol study. SETTING: Tertiary health care center in Montreal, Quebec.
      PATIENTS: Twelve patients scheduled for colonic resection were randomly allocated
      to undergo either laparoscopic (n = 6) or open (n = 6) surgery. INTERVENTIONS:
      Patients underwent a 6-hour stable isotope infusion study (3 hours fasted and 3
      hours fed with dextrose infusion) on postoperative day 2. Whole-body protein
      breakdown and synthesis, amino acid oxidation, and endogenous glucose production
      and clearance were measured during the postabsorptive state using L-[1
      (13)C]leucine and [6,6-(2)H(2)]glucose. Gas exchange and plasma concentrations of
      metabolites and hormones were also measured. MAIN OUTCOME MEASURES: Endogenous
      glucose production and whole-body protein breakdown during the fasted and fed
      states. RESULTS: In the fasted state, laparoscopy did not affect protein and
      glucose metabolism. Dextrose infusion suppressed endogenous glucose production in
      both groups, with the greatest extent in the laparoscopic group (P = .01). Higher
      respiratory quotients (P = .001) in the latter group also indicated increased
      exogenous glucose oxidation. Neither surgical approach nor nutrition affected
      aspects of protein metabolism. CONCLUSIONS: Laparoscopy for colon resection
      facilitates whole-body glucose uptake and utilization and oxidation of exogenous
      glucose with no protein-sparing effect. The laparoscopic approach modulates
      gluconeogenesis, although it is not sufficient in the presence of exogenous
      energy to promote nitrogen retention.

PMID- 15967909
TI  - Mentoring surgeons in private and academic practice.
AB  - Mentoring is an essential component of a successful career in any profession, and
      these relationships are beginning to be explored in great detail in academic
      surgery. However, it is equally important for surgeons in private practice, and
      this area has not received nearly as much attention in the literature. The goals
      for both are similar and include providing career advice, guidance, and
      counseling, with the only regard being the success of the junior associate. In
      private practice, the mentor can be a senior colleague who may or may not be part
      of one's group practice. In academia, it may be someone at another university,
      although proximity is preferable. It may be necessary to repeat the search for a
      mentor more than once before a successful relationship evolves. This complex
      process must be mastered if one is to be successful in either academia or private
      practice.

PMID- 15967910
TI  - Alexis Carrel (1873-1944): Nobel Laureate, 1912.

PMID- 15967911
TI  - Image of the month. A second insulinoma.

PMID- 15967912
TI  - Successful treatment of recalcitrant pemphigus vulgaris and pemphigus vegetans
      with etanercept and carbon dioxide laser.

PMID- 15967913
TI  - Uncovering histologic criteria with prognostic significance in toxic epidermal
      necrolysis.
AB  - OBJECTIVE: To identify histologic criteria and prognostic significance in
      patients with toxic epidermal necrolysis (TEN), a frequently lethal disease that
      usually represents an adverse drug reaction. DESIGN: Retrospective analysis of
      clinical records and histologic material from a 10-year period (1994-2004). Two
      investigators blinded to clinical data reviewed hematoxylin-eosin-stained
      sections. SETTING: North American tertiary care, university-based burn unit.
      Patients Thirty-seven patients treated for TEN between 1994 and 2004 who had
      sloughing of 30% or more of their total body surface area and who underwent skin
      punch biopsies immediately following admission. Main Outcome Measure The degree
      of dermal mononuclear (DM) inflammation was graded (sparse, moderate, or
      extensive) at least 2 high-power fields (HPF) away from the perimeter of
      epidermal detachment, and the mean number of DM cells/5 HPF was quantified for
      each patient. Clinical records were reviewed and the following data extracted:
      age, history of cancer, percentage of total body surface area slough, heart rate,
      and serum glucose, bicarbonate, and serum urea nitrogen values on admission.
      Severity scores for TEN (SCORTEN) were calculated, and clinical outcome was
      recorded as survived or died during hospitalization. RESULTS: Extent of
      inflammation was assessed by categorizing the mean +/- SD DM cell counts as
      follows: sparse, 161 +/- 36 cells/HPF (n = 15); moderate, 273 +/- 76 cells/HPF (n
      = 15); and extensive, 392 +/- 124 cells/HPF (n = 7). There was good concordance
      between observer ratings (P<.001). While 73% of patients (n = 11) with sparse
      inflammation survived, only 47% (n = 7) with moderate and 29% (n = 2) with
      extensive inflammation survived. The accuracy in predicting patient outcome was
      65% using grade of inflammation, 68% with mean cell count, and 71% with SCORTEN.
      CONCLUSIONS: There is a histologic spectrum with TEN that ranges from sparse to
      extensive DM inflammation, and degree of inflammation predicts clinical outcome
      approximately as well as SCORTEN. Future clinical trials should consider the
      possibility that various patient subsets exist within the TEN population, and a
      role for immunocytes needs to be critically reevaluated in this devastating
      disease.

PMID- 15967914
TI  - Prediction of survival for patients with bullous pemphigoid: a prospective study.
AB  - OBJECTIVE: To identify the prognostic factors of bullous pemphigoid (BP). DESIGN:
      Prospective study of patients with BP included in a randomized, controlled trial.
      SETTING: Twenty dermatology departments in France. Patients One hundred seventy
      patients with BP initially treated with a 40-g/d dosage of clobetasol propionate
      cream (testing sample) and 171 patients initially treated with oral
      corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the
      extent of BP (validation samples). MAIN OUTCOME MEASURES: The end point was
      overall survival during the first year after BP diagnosis. From the testing
      sample, associations of clinical and biological variables with overall survival
      were assessed using univariate and multivariate analyses. Selected predictors
      were included in a prognostic model. To verify that these predictors were not
      dependent on the treatment used, the model was then validated independently on
      the 2 series of BP patients treated with oral corticosteroids. RESULTS: Median
      age of the BP patients included in the testing sample was 83 years. The 1-year
      Kaplan-Meier survival rate was 74%. From univariate analysis, the main
      deleterious predictors were demographic factors (ie, older age and female sex),
      associated medical conditions (ie, cardiac insufficiency, history of stroke, and
      dementia), and low Karnofsky score, which is a measure of the patient's general
      condition. No factors directly related to BP, in particular extent of cutaneous
      lesions, were shown to be related to the patients' prognosis. From multivariate
      analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared
      independently predictive of death. From the Cox model including these 2
      predictors, the predicted 1-year survival rates were 90% (95% confidence interval
      [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than
      40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score
      greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with
      Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than
      83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions
      of patients from the validation samples appeared clearly separated according to
      these 4 categories and were in close agreement with corresponding predicted 1
      year survival rates obtained from the testing sample. CONCLUSIONS: The prognosis
      of patients with BP is influenced by age and Karnofsky score. These predictors
      are easy to use and should facilitate the management of BP.

PMID- 15967915
TI  - Dapsone as a glucocorticoid-sparing agent in maintenance-phase pemphigus
      vulgaris.
AB  - OBJECTIVE: To determine the effect of dapsone on glucocorticoid-dependent
      patients with active or maintenance-phase pemphigus vulgaris. DESIGN:
      Retrospective study of consecutive patients treated with dapsone. SETTING:
      University of Pennsylvania, Philadelphia (a tertiary referral hospital). Patients
      We observed 9 consecutive adult patients with pemphigus vulgaris being treated
      with immunosuppressants who were unable to taper prednisone use without abrupt
      worsening of their disease.Interventions Dapsone treatment added to prednisone
      and other immunosuppressive therapy. Main Outcome Measure Steroid dosage.
      RESULTS: All patients were unable to taper their steroid dose during the 3 months
      prior to the initiation of dapsone therapy or had active disease that was not
      well controlled by prednisone prior to dapsone treatment. With the exception of 1
      patient with uncontrolled disease, all 9 patients were able to taper their
      steroid dose below the adrenal replacement level during dapsone treatment.
      Maintenance-phase patients taking 15 mg/d or more of prednisone (n = 5)
      experienced a mean +/- SEM drop of 67% +/- 7.1% in prednisone dose by 4 months of
      maximal dapsone treatment and an 84% +/- 3.5% drop in prednisone dose after 8
      months of dapsone treatment. CONCLUSIONS: These retrospective study findings
      suggest that dapsone reduces steroid dependence in patients with pemphigus
      vulgaris, provided they are in the maintenance phase of their disease. These data
      support the need for a prospective, randomized trial to confirm these findings.

PMID- 15967916
TI  - Usefulness of BP180 NC16a enzyme-linked immunosorbent assay in the serodiagnosis
      of pemphigoid gestationis and in differentiating between pemphigoid gestationis
      and pruritic urticarial papules and plaques of pregnancy.
AB  - BACKGROUND: Pemphigoid gestationis (PG) is a rare pregnancy-associated
      subepidermal immunobullous disease that targets hemidesmosomal proteins,
      particularly BP180. Clinically, PG can resemble the eruption known as polymorphic
      urticarial papules and plaques of pregnancy (PUPPP), and accurate differentiation
      between these 2 pruritic pregnancy dermatoses has important implications for
      fetal and maternal prognoses. Results of epitope mapping studies show that IgG
      autoantibodies in up to 90% of PG serum samples target the well-defined membrane
      proximal NC16a domain of BP180. OBJECTIVE: To examine the usefulness of a
      commercially available NC16a domain enzyme-linked immunosorbent assay in the
      serodiagnosis of PG and in the differentiation of PG from PUPPP. PARTICIPANTS: A
      total of 412 women consisting of pretreatment patients with PG (n = 82), patients
      with PUPPP (n = 164), and age- and sex-matched controls (n = 166). METHODS: All
      serum samples were assayed in duplicate. Receiver operating characteristic
      analyses were performed to determine a cutoff value for the diagnosis of PG and
      for differentiation from PUPPP and controls. RESULTS: A cutoff value of 10 enzyme
      linked immunosorbent assay units was associated with specificity and sensitivity
      of 96%. CONCLUSIONS: The NC16a enzyme-linked immunosorbent assay is highly
      sensitive and highly specific in differentiating PG from PUPPP, and it is
      potentially a valuable tool in the serodiagnosis of PG.

PMID- 15967917
TI  - Incidence rates, costs, severity, and work-related factors of occupational
      dermatitis: a workers' compensation analysis of Oregon, 1990-1997.
AB  - Objectives To extend and update past research on occupational dermatitis by
      examining recent workers' compensation claims data. DESIGN: Retrospective
      analysis of workers' compensation claims from Oregon (1990-1997). SETTING: All
      dermatitis-related workers' compensation claims were merged with US census data
      to estimate rates of dermatitis by age, sex, occupation, and industry. Associated
      claim costs and disability times were also calculated from these data.
      PARTICIPANTS: All individuals with accepted dermatitis claims (N = 611) were
      included in the analyses. MAIN OUTCOME MEASURES: The overall claim rates of
      individuals by age, sex, industry, and occupation were estimated. Total costs and
      average disability time were computed. Monthly patterns of dermatitis claims were
      examined. RESULTS: The average claim rate of occupational dermatitis was
      estimated to be 5.73 per 100 000 workers (95% confidence interval, 5.66-5.80).
      Statistically significant differences (P<.001) in claim rates by age, sex,
      industry, and occupation were found. More than 47% of all claimants had 1 year of
      job tenure or less. Employees in the farming, forestry, and fishing occupations
      and industries had significantly higher claim rates compared with employees in
      other occupations. The average cost per claim was $3552, and the average
      disability time was 23.9 days. Some temporal trends in claim rates were observed.
      CONCLUSIONS: Occupational dermatitis remains a significant problem in workplace
      settings. In addition, certain types of occupations and industries seem to be
      particularly affected by occupational dermatitis. Interventions may be
      particularly valuable for workers with little job tenure.

PMID- 15967918
TI  - Variation in the diagnosis, treatment, and management of melanoma in situ: a
      survey of US dermatologists.
AB  - OBJECTIVE: To assess current practices of US dermatologists regarding the
      diagnosis, treatment, and management of melanoma in situ (MIS). DESIGN: Survey.
      PARTICIPANTS: A total of 1200 dermatologists randomly selected from the American
      Board of Medical Specialists Directory of Board Certified Medical Specialists.
      MAIN OUTCOME MEASURES: Results based on 597 questionnaires returned. RESULTS: The
      overall response rate was 63% (597 of 945 eligible participants). To aid in
      clinical assessment, respondents reported using a magnifying lens (57.4%) and
      dermoscopy (17.4%). Most dermatologists preferred excisional and saucerization
      biopsies as the method of choice for sampling. A large percentage of physicians
      (78.9%) preferentially used dermatopathologists for the evaluation of the
      majority of pigmented lesions. Although most respondents would not
      unquestioningly accept a benign pathology diagnosis when there was a clinical
      suspicion of MIS, 16.1% would accept a pathologist's diagnosis without further
      action. There was no consensus on the appropriate surgical margins or depth of
      excision for MIS. Of the respondents who characterized MIS as premalignant and
      malignant, 63.2% and 46.4%, respectively, did not know what percentage of MISs
      would progress to metastatic disease if left untreated. CONCLUSIONS: Considerable
      variability exists in the clinical concept and management of MIS. Dermoscopy is
      underutilized. The true nature of the evolution of MIS is unknown. Surgical
      margins and depth of excision need to be standardized to help dermatologists
      manage disease. Further research in the specific area of MIS is warranted to
      develop clear guidelines in the management and prevention of further disease.

PMID- 15967919
TI  - Impact of thorough block sampling in the histologic evaluation of melanomas.
AB  - OBJECTIVE: To determine if changes in histologic parameters obtained from
      intermittent sampling of the entire block correlated with differences in
      prognosis and management. DESIGN: Prospective analysis of skin biopsy specimens.
      SETTING: Skin pathology laboratory. Patients One hundred consecutive patients
      with an unequivocal diagnosis of melanoma. Interventions Two initial slides were
      prepared from serial sections of 5-mum thickness. When evaluation of the initial
      slide revealed melanoma, 5 additional slides were obtained by sectioning at
      levels through the entire block. Breslow depth, Clark level, ulceration, tumor
      infiltrating lymphocytes, vascular invasion, regression, presence of a precursor
      lesion, and histologic type of melanoma for the first slide and the additional 6
      slides were analyzed and compared. RESULTS: Review of the additional 6 slides
      from level sectioning revealed a greater maximum tumor thickness than was evident
      from the original slide in 43% of the cases. In 10 of these cases, the new
      maximum tumor thickness measurements changed the surgical management of the
      patients. Ulceration was observed in 6% of cases on the initial slides, and an
      additional 3% of lesions were found to have ulceration on levels. The level of
      invasion was deeper than originally found in 10% of the cases. CONCLUSIONS: Level
      sectioning through an entire block of a melanoma specimen provides additional
      information in the classification and management of melanomas. Extensive block
      sampling will result in more accurate information regarding histologic parameters
      of melanoma, but the yield must be balanced with the extra cost of materials,
      time, labor, and the potential disadvantage of not retaining tissue for future
      use.

PMID- 15967920
TI  - The role of microsatellites as a prognostic factor in primary malignant melanoma.
AB  - OBJECTIVE: To determine the impact of microsatellites as a prognostic factor in
      primary cutaneous melanoma. DESIGN: Retrospective cohort study. SETTING: Tertiary
      referral center. Patients A total of 504 patients with a history of primary
      melanoma observed for 2 years or having experienced a first relapse. MAIN OUTCOME
      MEASURES: Overall survival (OS) and relapse-free survival (RFS). RESULTS: Forty
      five patients had evidence of microsatellites in their primary melanoma. Presence
      of microsatellites significantly correlated with the presence of several other
      histologic high-risk factors such as tumor thickness, ulceration, Clark level,
      vascular factors, and mitotic rate. Univariate analysis demonstrated decreased
      RFS and OS in patients with microsatellites. Presence of microsatellites was
      associated with increased locoregional metastasis but not distant metastasis. In
      multivariate analysis, with the inclusion of 6 other clinical and histologic
      factors, presence of microsatellites was a significant predictor of RFS but not
      OS. Patients with clinical macrosatellites had a trend toward worsening OS
      compared with those with microsatellites. CONCLUSIONS: The presence of
      microsatellites is intimately tied to other markers of melanoma aggressiveness.
      Microsatellites appear to predict locoregional relapse and RFS but neither
      distant metastasis nor OS. These results may have implications for patient care
      as well as the inclusion of microsatellites in stage III of the current
      classification.

PMID- 15967921
TI  - Early detection of thick melanomas in the United States: beware of the nodular
      subtype.
AB  - BACKGROUND: Incidence and mortality of melanoma in the United States have risen
      steeply. Part of this mortality increase may be related to late detection of
      biologically aggressive nodular melanomas. We determined trends in distribution
      of thin and thick melanoma, with emphasis on the histopathologic subtype nodular
      melanoma. METHODS: Surveillance, Epidemiology, and End Results melanoma incidence
      data for whites were obtained for 1988 through 1999 and stratified according to
      histologic subtype: lentigo maligna melanoma, superficial spreading melanoma,
      nodular melanoma, other, and not otherwise specified (NOS); thickness: 0-0.99 mm,
      1.00 mm-1.99 mm, and > or =2.0 mm; patient age (0-49, 50+); gender; and year
      (1988-1991, 1992-1995, 1996-1999). Comparison of tumor thickness between strata
      was defined by year of diagnosis, sex, age, and histologic subtype. RESULTS: The
      number of new melanoma cases in a 3-year period increased 60% from 1988-1991 (n =
      9132) to 1996-1999 (n = 14 575). The proportion of thick melanomas (> or =2 mm)
      remained relatively stable during the 12 study years. Nodular melanoma comprised
      9% of all recorded cases but 34% of melanomas 2 mm or larger, including melanoma
      not otherwise specified (NOS), and nearly 50% of all melanomas 2 mm or larger
      when NOS cases were excluded. In contrast, superficial spreading melanoma was
      almost uniformly diagnosed as an early tumor, mostly (77%) presenting as thin
      melanoma (<1 mm) and with only 7% presenting as thick melanoma (> or =2 mm).
      CONCLUSIONS: A substantial number of thick melanomas in the United States are of
      the nodular subtype, and median thickness of nodular melanoma has not changed
      during the 12 years of study. New strategies are needed to decrease the incidence
      of thick melanoma in the United States.

PMID- 15967922
TI  - The association of Medicare health care delivery systems with stage at diagnosis
      and survival for patients with melanoma.
AB  - OBJECTIVE: To evaluate differences in the stage at diagnosis and survival for
      melanoma between the 2 most common types of Medicare health care delivery
      systems, fee-for-service (FFS) and managed care (health maintenance organizations
      [HMOs]), in the United States during the period from January 1, 1985, through
      December 31, 1994. DESIGN: We used a linkage of 2 national databases, ie, the
      Medicare database from the Centers for Medicare and Medicaid Services (formerly
      the Health Care Financing Administration) and the National Cancer Institute
      Surveillance, Epidemiology, and End Results program database, to evaluate
      differences in demographic data, stage at diagnosis, and survival for melanoma
      between the HMO and FFS groups. Patients A population of 4608 patients (62% men;
      92% white). RESULTS: We found an earlier stage of diagnosis for the HMO group
      compared with the FFS group for melanoma as the first cancer diagnosis, but this
      did not persist when melanoma was the second or a later cancer diagnosis. For
      patients with melanoma as the first cancer diagnosis, improved survival was
      related to earlier stage at diagnosis. CONCLUSIONS: Differences exist in stage at
      diagnosis between patients in HMOs compared with those in FFS health care plans.
      This is likely due in part to utilization of services or access to care for
      patients in HMOs, and may be similar to that of patients in FFS plans with a
      previous cancer diagnosis before their diagnosis of melanoma. We did not find an
      increased risk of diagnosis with a late-stage cancer among patients with vs those
      without a previous cancer diagnosis. Improved survival appears to be related to
      earlier stage at diagnosis.

PMID- 15967923
TI  - Recurrence of alopecia areata in a patient receiving etanercept injections.
AB  - BACKGROUND: Alopecia areata is a common condition of patchy hair loss that has
      been postulated to have an autoimmune pathogenesis involving inflammatory
      cytokines, including tumor necrosis factor (TNF) alpha. Etanercept is a novel
      medication that blocks TNF-alpha-mediated processes. We report a case involving
      the recurrence of alopecia areata in a patient receiving etanercept.
      OBSERVATIONS: We describe a 49-year-old man with a history of rheumatoid
      arthritis and alopecia areata who developed a recurrence of his alopecia areata
      while being treated with etanercept for more than 2 years. CONCLUSIONS: The anti
      TNF-alpha effect of etanercept therapy may not be sufficient to prevent the
      recurrence of alopecia areata. The possible role of TNF-alpha in the pathogenesis
      of alopecia areata may be called into question if our observation is repeated.

PMID- 15967924
TI  - Dysplastic pointillist nevus.
AB  - BACKGROUND: Three cases of pointillist nevus, which is a distinctive clinical
      type of benign melanocytic nevus with variegated pigment, have been described in
      the literature to date. OBSERVATIONS: A 24-year-old man presented with an
      acquired melanocytic lesion composed of multiple tiny pigmented dots. Dermoscopy
      revealed multiple brown globules on a reddish skin-colored background, and
      histologic examination demonstrated architectural disorder with cytologic atypia.
      Conclusion To the best of our knowledge, we report a case of dysplastic
      pointillist nevus.

PMID- 15967925
TI  - Temporal case clustering in pityriasis rosea: a regression analysis on 1379
      patients in Minnesota, kuwait, and diyarbakir, Turkey.
AB  - OBJECTIVE: To detect temporal case clustering in patients with pityriasis rosea
      in different geographic locations. DESIGN: Regression analysis of dates on which
      1379 patients were diagnosed as having pityriasis rosea in 3 different geographic
      locations. The control data consisted of dates of diagnosis of patients with
      psoriasis in the same settings. SETTING: Dermatology clinics in Kuwait,
      Minnesota, and Diyarbakir, Turkey.Patients Patients with pityriasis rosea and
      psoriasis seeking care in the clinics. RESULTS: Three significant positive
      clusters (P = .005, P =.001, and P =.01, respectively) and 1 significant negative
      cluster (P<.001) were detected in these series of patients. No cluster was
      detected in 2 corresponding series of patients with psoriasis in Kuwait and
      Turkey. CONCLUSION: Temporal case clustering exists in pityriasis rosea.

PMID- 15967926
TI  - Evidence-based medicine: do we use guidelines or mindlines? Commentary on:
      Evidence-based guidelines or collectively constructed "mindlines?" ethnographic
      study of knowledge management in primary care. Gabbay J, le May G BMJ.
      2004;329:1013.

PMID- 15967928
TI  - A slowly enlarging umbilical nodule--quiz case. Diagnosis: Verrucous carcinoma.

PMID- 15967927
TI  - Cell-mediated immunologic mechanism and severity of TEN.

PMID- 15967929
TI  - Eczematous changes on the hands--quiz case. Diagnosis: "Mechanic's hands" as part
      of the antisynthetase syndrome.

PMID- 15967930
TI  - Seborrheic distributed papules with palmoplantar hyperkeratosis--quiz case.
      Diagnosis: Ichthyosis hystrix, Curth-Macklin type.

PMID- 15967931
TI  - Psoriasiform plaques and periodontal infection--quiz case. Diagnosis: Papillon
      Lefevre syndrome.

PMID- 15967932
TI  - Imiquimod and squamous cell cancer.

PMID- 15967933
TI  - 0.1% tacrolimus ointment for the treatment of intertrigo.

PMID- 15967934
TI  - Toxic epidermal necrolysis associated with concomitant use of lamotrigine and
      carbamazepine: a case report.

PMID- 15967935
TI  - Plasma cell vulvitis: a rare cause of intractable vulvar pruritus.

PMID- 15967936
TI  - Vulvovaginitis and perineal cellulitis due to group a streptococcus in an adult
      woman.

PMID- 15967937
TI  - Estrogen dermatitis: treatment with progestin-only pill.

PMID- 15967938
TI  - Small eumycetic mycetoma due to black grain.

PMID- 15967939
TI  - Chronic cutaneous fusariosis.

PMID- 15967940
TI  - A man with a reddish stained wash cloth.

PMID- 15967941
TI  - A patient with nasal ulceration after brain surgery.

PMID- 15967942
TI  - Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman
      syndrome: an uncommon lipid storage disease.

PMID- 15967943
TI  - Mondor disease associated with physical strain: report of 2 cases.

PMID- 15967944
TI  - Deja vu all over again: skin cap still contains a high-potency
      glucocorticosteroid.

PMID- 15967945
TI  - Dermoscopy of sebaceous hyperplasia.

PMID- 15967946
TI  - Physicians, it's in your court now.

PMID- 15967947
TI  - Supreme disagreement: the highest court affirms an empty right.

PMID- 15967948
TI  - Supreme Court slaps for-sale sign on medicare.

PMID- 15967949
TI  - Why should clinical trials be registered?

PMID- 15967951
TI  - Difficulties of peace-building in Nepal.

PMID- 15967953
TI  - Summary Basis of Decision in context.

PMID- 15967954
TI  - Tintin in CMAJ.

PMID- 15967955
TI  - Tintin in CMAJ.

PMID- 15967956
TI  - [Tintin in CMAJ].

PMID- 15967957
TI  - Tintin in CMAJ.

PMID- 15967958
TI  - Training pediatricians.

PMID- 15967960
TI  - Tintin in CMAJ.

PMID- 15967962
TI  - Radiologists, physicians push for PET scans.

PMID- 15967963
TI  - Quebec doubling PET capacity.

PMID- 15967964
TI  - New US guidelines for research on human embryos.

PMID- 15967965
TI  - Conditional okay for cannabis prescription drug.

PMID- 15967966
TI  - Can NSAIDs contribute to Alzheimer's disease?

PMID- 15967967
TI  - Congenital rubella syndrome despite maternal antibodies.

PMID- 15967968
TI  - A refresher on rubella.

PMID- 15967969
TI  - In patients with early prostate cancer, is surgery better than watchful waiting?

PMID- 15967970
TI  - A 37-year-old woman with fever and abdominal pain.

PMID- 15967971
TI  - Capability of ischemia-modified albumin to predict serious cardiac outcomes in
      the short term among patients with potential acute coronary syndrome.
AB  - BACKGROUND: Ischemia-modified albumin (IMA) has been suggested as a marker of
      cardiac ischemia. Little, however, is known about its capacity to predict short
      term serious cardiac outcomes (death, myocardial infarction, congestive heart
      failure, serious arrhythmia, or refractory ischemic cardiac pain) in patients
      arriving at the emergency department with symptoms that may indicate cardiac
      ischemia. METHODS: We screened 546 patients over a 4-week period, of whom 189
      fulfilled our entry criteria by presenting to an emergency department with
      potential cardiac-ischemia symptoms within 6 hours after chest pain, seeing an
      emergency physician who chose to order a troponin I test, and having no serious
      cardiac outcome before the troponin result became available. We followed the
      study patients for 72 hours to determine if any experienced a serious cardiac
      outcome. We calculated the likelihood ratios (LRs) of IMA findings predicting
      serious cardiac outcomes that could not be diagnosed at presentation with current
      techniques. RESULTS: Of the 189 patients, 24 had a serious cardiac outcome within
      72 hours after their arrival at the emergency department. The likelihood ratios
      for IMA measurement within 6 hours after chest pain predicting a serious cardiac
      outcome within the next 72 hours were 1.35 (95% confidence interval [CI] 0.315
      5.79) for IMA < or = 80 U/mL and 0.98 (95% CI 0.86- 1.11) for IMA > 80 U/mL.
      CONCLUSIONS: These data suggest that in patients presenting with chest pain who
      have not yet experienced a serious cardiac event, IMA is a poor predictor of
      serious cardiac outcomes in the short term.

PMID- 15967972
TI  - Liposomal lidocaine to improve procedural success rates and reduce procedural
      pain among children: a randomized controlled trial.
AB  - BACKGROUND: Historically, children have been undertreated for their pain, and
      they continue to undergo painful cutaneous procedures without analgesics. A new
      topical anesthetic, liposomal lidocaine 4% cream (Maxilene, RGR Pharma, Windsor,
      Ont.), has become available. It has pharmacologic properties that are superior to
      other topical anesthetics, including an onset of action of only 30 minutes. We
      sought to determine the success rate of cannulation, analgesic effectiveness,
      procedure duration and rate of adverse skin reactions when liposomal lidocaine is
      used before intravenous cannulation of children. METHODS: In this double-blind
      randomized controlled trial, children aged 1 month to 17 years received liposomal
      lidocaine or placebo before cannulation. Success on first cannulation attempt was
      recorded, and, among children 5 years and older, pain was evaluated before and
      after the attempt by the child, parents and research assistant using a validated
      measure (Faces Pain Scale-Revised). For children younger than 5 years, pain was
      evaluated by the parents and research assistant only. The total duration of the
      procedure and adverse skin reactions were also recorded. RESULTS: Baseline
      characteristics did not differ (p > 0.05) between children who received liposomal
      lidocaine (n = 69) and those who received placebo (n = 73). Cannulation on the
      first attempt was achieved in 74% of children who received liposomal lidocaine
      compared with 55% of those who received placebo (p = 0.03). Among children 5
      years of age and older (n = 67), lower mean pain scores during cannulation were
      reported by those receiving liposomal lidocaine (p = 0.01). Similarly, lower mean
      pain scores during cannulation were reported by the parents and research
      assistant for all children who received liposomal lidocaine than for all those
      who received placebo (p < 0.001). The mean total procedure duration was shorter
      with liposomal lidocaine (6.7 v. 8.5 minutes; p = 0.04). The incidence of
      transient dermal changes was 23% in both groups (p = 1.0). CONCLUSIONS: Use of
      liposomal lidocaine was associated with a higher intravenous cannulation success
      rate, less pain, shorter total procedure time and minor dermal changes among
      children undergoing cannulation. Its routine use for painful cutaneous procedures
      should be considered whenever feasible.

PMID- 15967973
TI  - When prognosis precedes diagnosis: putting the cart before the horse.

PMID- 15967974
TI  - Do no harm--but first, do not hurt.

PMID- 15967975
TI  - Modern antipsychotic drugs: a critical overview.
AB  - Conventional antipsychotic drugs, used for a half century to treat a range of
      major psychiatric disorders, are being replaced in clinical practice by modern
      "atypical" antipsychotics, including aripiprazole, clozapine, olanzapine,
      quetiapine, risperidone and ziprasidone among others. As a class, the newer drugs
      have been promoted as being broadly clinically superior, but the evidence for
      this is problematic. In this brief critical overview, we consider the
      pharmacology, therapeutic effectiveness, tolerability, adverse effects and costs
      of individual modern agents versus older antipsychotic drugs. Because of
      typically minor differences between agents in clinical effectiveness and
      tolerability, and because of growing concerns about potential adverse long-term
      health consequences of some modern agents, it is reasonable to consider both
      older and newer drugs for clinical use, and it is important to inform patients of
      relative benefits, risks and costs of specific choices.

PMID- 15967976
TI  - The elasticity of an individual fibrin fiber in a clot.
AB  - A blood clot needs to have the right degree of stiffness and plasticity to stem
      the flow of blood and yet be digestable by lytic enzymes so as not to form a
      thrombus, causing heart attacks, strokes, or pulmonary emboli, but the origin of
      these mechanical properties is unknown. Clots are made up of a three-dimensional
      network of fibrin fibers stabilized through ligation with a transglutaminase,
      factor XIIIa. We developed methods to measure the elastic moduli of individual
      fibrin fibers in fibrin clots with or without ligation, using optical tweezers
      for trapping beads attached to the fibers that functioned as handles to flex or
      stretch a fiber. Here, we report direct measurements of the microscopic
      mechanical properties of such a polymer. Fibers were much stiffer for stretching
      than for flexion, as expected from their diameter and length. Elastic moduli for
      individual fibers in plasma clots were 1.7 +/- 1.3 and 14.5 +/- 3.5 MPa for
      unligated and ligated fibers, respectively. Similar values were obtained by other
      independent methods, including analysis of measurements of fluctuations in bead
      force as a result of Brownian motion. These results provide a basis for
      understanding the origin of clot elasticity.

PMID- 15967977
TI  - Directed evolution of D-sialic acid aldolase to L-3-deoxy-manno-2-octulosonic
      acid (L-KDO) aldolase.
AB  - An efficient L-3-deoxy-manno-2-octulosonic acid (L-KDO) aldolase was created by
      directed evolution from the Escherichia coli D-Neu5Ac (N-acetylneuraminic acid, D
      sialic acid) aldolase. Five rounds of error-prone PCR and iterative screening
      were performed with sampling of 10(3) colonies per round. The specificity
      constant (kcat/Km) of the unnatural sugar L-KDO is improved to a level equivalent
      to the wild-type D-sialic acid aldolase for its natural substrate, D-Neu5Ac. The
      final evolved enzyme exhibits a >1,000-fold improved ratio of the specificity
      constant [kcat/Km (L-KDO)]/[kcat/Km (D-sialic acid)]. The protein sequence of the
      evolved aldolase showed eight amino acid changes from the native enzyme, with all
      of the observed changes occurring outside of the active site. Our effort
      demonstrates that an enzyme can be rapidly altered to accept enantiomeric
      substrates with screening of a small population of colonies iteratively toward
      the target substrate with improved catalytic efficiency. This work provides a
      method for the synthesis of enantiomeric sugars and for the study of enantiomeric
      catalysis affected by remote mutations.

PMID- 15967978
TI  - Immunoproteasomes: regulating the regulator.

PMID- 15967979
TI  - The relationship between memory retrieval and memory extinction.

PMID- 15967980
TI  - The discovery of asymptotic freedom and the emergence of QCD.

PMID- 15967981
TI  - Depletion of BRCA1 impairs differentiation but enhances proliferation of mammary
      epithelial cells.
AB  - Cumulative evidence indicates that breast cancer-associated gene 1 (BRCA1)
      participates in DNA damage repair and cell-cycle checkpoint control, serving as a
      tumor susceptibility gene to maintain the global genomic stability. However,
      whether BRCA1 has a direct role in cell proliferation and differentiation, two
      key biological functions in tumorigenesis, remains unclear. Here we demonstrate
      BRCA1 mediates differentiation of mammary epithelial cell (MEC) for acinus
      formation by using the in vitro 3D culture system. Reduction of BRCA1 in MEC by
      RNA interference impairs the acinus formation but enhances proliferation. Such
      aberrations can be rescued by expression of wild-type BRCA1 as well as a mutant
      at the RAD50-binding domain but not at the C-terminal BRCT domain, suggesting
      that the C-terminal BRCT domain has a critical role in these processes.
      Consistently, depletion of BRCA1 up-regulates the gene expression for
      proliferation but down-regulates that for differentiation. Moreover, application
      of the medium conditioned by differentiating normal MEC can reverse the
      phenotypes of differentiation-defective breast cancer cells bearing reduced BRCA1
      functions. Our observation implies BRCA1 is involved in secretion of certain
      paracrine/autocrine factors that induce MEC differentiation in response to
      extracellular matrix signals, providing, in part, an explanation for the
      etiological basis of either sporadic or familial breast cancer due to the loss or
      reduction of BRCA1.

PMID- 15967982
TI  - Genetic evidence for a protein-kinase-A-mediated presynaptic component in NMDA
      receptor-dependent forms of long-term synaptic potentiation.
AB  - The synaptic vesicle protein Rab3A is a small GTP-binding protein that interacts
      with rabphilin and RIM1alpha, two presynaptic substrates of protein kinase A
      (PKA). Mice lacking RIM1alpha and Rab3A have a defect in PKA-dependent and NMDA
      receptor (NMDAR)-independent presynaptic long-term potentiation (LTP) at
      hippocampal mossy-fiber and cerebellar parallel-fiber synapses. In contrast, the
      NMDAR-dependent and PKA-independent early phase of LTP at hippocampal CA3-CA1
      synapses does not require these presynaptic proteins. Here, we ask whether Rab3A
      and RIM1alpha participate in forms of LTP that require both PKA and NMDAR
      activation. We find that Rab3A is necessary for corticoamygdala LTP and late
      phase LTP at CA3-CA1 synapses, two forms of LTP that require NMDAR and PKA
      activation. The latter form of LTP also requires RIM1alpha. These results provide
      genetic evidence that presynaptic proteins are required in LTP induced through
      the postsynaptic activation of NMDARs. Thus Rab3A and its effectors are general
      modules for four distinct types of PKA-dependent LTP in the brain.

PMID- 15967983
TI  - Degrees and kinds of selection in spontaneous neoplastic transformation: an
      operational analysis.
AB  - Spontaneous neoplastic transformation develops within days in the NIH 3T3 line of
      cells through differential inhibition of their proliferation under contact
      inhibition. A small fraction of the population continues to multiply after
      saturation density is reached and is selected to progressively increase
      saturation density in successive rounds of confluence. The degree of selection at
      confluence depends on the extent of proliferation of some cells in a
      heterogeneous population. The development of transformed foci is an extension of
      the same selective process that increases saturation density. The expression of
      the foci is enhanced with increases in the saturation density of the surrounding
      cells. Transformation is also induced by moderately reducing the concentration of
      calf serum in the medium during low-density passages, which allows selection of
      cells that require less growth factor. Further stepwise reductions in serum
      increase the degree of transformation. Contact inhibition and reduction in serum
      concentration select for the same phenotype of cell that increases saturation
      density and generates transformed foci. There is mounting evidence that selection
      is a major factor in the development of common epithelial tumors of humans, but
      it extends over decades rather than days, and the in vivo microenvironment
      selects from more stable populations of cells than those in culture. The many
      progressive levels of increased saturation density and transformed focus
      formation suggest that a very large number of genes participate in neoplastic
      development. The operational model of variation and selection presented here may
      aid in understanding chemical carcinogenesis and cancer recurrence after
      chemotherapy.

PMID- 15967984
TI  - An obligately photosynthetic bacterial anaerobe from a deep-sea hydrothermal
      vent.
AB  - The abundance of life on Earth is almost entirely due to biological
      photosynthesis, which depends on light energy. The source of light in natural
      habitats has heretofore been thought to be the sun, thus restricting
      photosynthesis to solar photic environments on the surface of the Earth. If
      photosynthesis could take place in geothermally illuminated environments, it
      would increase the diversity of photosynthetic habitats both on Earth and on
      other worlds that have been proposed to possibly harbor life. Green sulfur
      bacteria are anaerobes that require light for growth by the oxidation of sulfur
      compounds to reduce CO2 to organic carbon, and are capable of photosynthetic
      growth at extremely low light intensities. We describe the isolation and
      cultivation of a previously unknown green sulfur bacterial species from a deep
      sea hydrothermal vent, where the only source of light is geothermal radiation
      that includes wavelengths absorbed by photosynthetic pigments of this organism.

PMID- 15967986
TI  - Real-time RNA profiling within a single bacterium.
AB  - Characterizing the dynamics of specific RNA levels requires real-time RNA
      profiling in a single cell. We show that the combination of a synthetic modular
      genetic system with fluorescence correlation spectroscopy allows us to directly
      measure in real time the activity of any specific promoter in prokaryotes. Using
      a simple inducible gene expression system, we found that induced RNA levels
      within a single bacterium of Escherichia coli exhibited a pulsating profile in
      response to a steady input of inducer. The genetic deletion of an efflux pump
      system, a key determinant of antibiotic resistance, altered the pulsating
      transcriptional dynamics and caused overexpression of induced RNA. In contrast
      with population measurements, real-time RNA profiling permits identifying
      relationships between genotypes and transcriptional dynamics that are accessible
      only at the level of the single cell.

PMID- 15967985
TI  - Regulation of dopaminergic transmission and cocaine reward by the Clock gene.
AB  - Although there are clear interactions between circadian rhythms and drug
      addiction, mechanisms for such interactions remain unknown. Here we establish a
      role for the Clock gene in regulating the brain's reward circuit. Mice lacking a
      functional Clock gene display an increase in cocaine reward and in the
      excitability of dopamine neurons in the midbrain ventral tegmental area, a key
      brain reward region. These phenotypes are associated with increased expression
      and phosphorylation of tyrosine hydroxylase (the rate-limiting enzyme in dopamine
      synthesis), as well as changes in several genes known to regulate dopamine
      activity in the ventral tegmental area. These findings demonstrate the
      involvement of a circadian-associated gene, Clock, in regulating dopamine
      function and cocaine reward.

PMID- 15967987
TI  - An alternative interpretation of the amyloid Abeta hypothesis with regard to the
      pathogenesis of Alzheimer's disease.
AB  - Alzheimer's disease is a complex neurodegenerative process that is believed to be
      due to the accumulation of short, hydrophobic peptides derived from amyloid
      precursor proteins by proteolytic cleavage. It is widely believed that these
      Abeta peptides are secreted into the extracellular spaces of the CNS, where they
      assemble into toxic oligomers that kill neurons and eventually form deposits of
      senile plaques. This essay explores the possibility that a fraction of these
      Abeta peptides never leave the membrane lipid bilayer after they are generated,
      but instead exert their toxic effects by competing with and compromising the
      functions of intramembranous segments of membrane-bound proteins that serve many
      critical functions. Based on the presence of shared amino acid sequences
      containing GxxG motifs, I speculate that accumulations of intramembranous Abeta
      peptides might affect the functions of amyloid precursor protein itself and the
      assembly of the PS1, Aph1, Pen 2, Nicastrin complex.

PMID- 15967988
TI  - Slaved diffusion in phospholipid bilayers.
AB  - The translational diffusion of phospholipids in supported fluid bilayers splits
      into two populations when polyelectrolytes adsorb at incomplete surface coverage.
      Spatially resolved measurements using fluorescence correlation spectroscopy show
      that a slow mode, whose magnitude scales inversely with the degree of
      polymerization of the adsorbate, coexists with a fast mode characteristic of
      naked lipid diffusion. Inner and outer leaflets of the bilayer are affected
      nearly equally. Mobility may vary from spot to spot on the membrane surface,
      despite the lipid composition being the same. This work offers a mechanism to
      explain how nanosized domains with reduced mobility arise in lipid membranes.

PMID- 15967989
TI  - Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of
      oocytes into preimplantation embryos.
AB  - Optimal development of fertilized eggs into preimplantation embryos is essential
      for reproduction. Although mammalian oocytes ovulated after luteinizing hormone
      (LH) stimulation can be fertilized and promoted into early embryos in vitro,
      little is known about ovarian factors important for the conditioning of eggs for
      early embryo development. Because LH interacts only with ovarian somatic cells,
      its potential regulation of oocyte functions is presumably mediated by local
      paracrine factors. We performed DNA microarray analyses of ovarian transcripts
      and identified brain-derived neurotrophic factor (BDNF) secreted by granulosa and
      cumulus cells as an ovarian factor stimulated by the preovulatory LH surge.
      Ovarian BDNF acts on TrkB receptors expressed exclusively in oocytes to enhance
      first polar body extrusion of oocytes and to promote the in vitro development of
      zygotes into preimplantation embryos. Furthermore, in vivo treatment with a Trk
      receptor inhibitor suppressed first polar body extrusion and the progression of
      zygotes into blastocysts. Thus, ovarian BDNF is important to nuclear and
      cytoplasmic maturation of the oocyte, which is essential for successful oocyte
      development into preimplantation embryos. Treatment with BDNF could condition the
      cultured oocytes for optimal progression into the totipotent blastocysts.

PMID- 15967990
TI  - Human thiopurine S-methyltransferase pharmacogenetics: variant allozyme
      misfolding and aggresome formation.
AB  - Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of thiopurine
      drugs. TPMT genetic polymorphisms represent a striking example of the potential
      clinical value of pharmacogenetics. Subjects homozygous for TPMT*3A, the most
      common variant allele for low activity, an allele that encodes a protein with two
      changes in amino acid sequence, are at greatly increased risk for life
      threatening toxicity when treated with standard doses of thiopurines. These
      subjects have virtually undetectable levels of TPMT protein. In this study, we
      tested the hypothesis that TPMT*3A might result in protein misfolding and
      aggregation. We observed that TPMT*3A forms aggresomes in cultured cells and that
      it aggregates in vitro, functional mechanisms not previously described in
      pharmacogenetics. Furthermore, there was a correlation among TPMT half-life
      values in rabbit reticulocyte lysate, aggresome formation in COS-1 cells, and
      protein aggregation in vitro for the three variant allozymes encoded by alleles
      that include the two TPMT*3A single-nucleotide polymorphisms. These observations
      were compatible with a common structural explanation for all of these effects, a
      conclusion supported by size-exclusion chromatography and CD spectroscopy. The
      results of these experiments provide insight into a unique pharmacogenetic
      mechanism by which common polymorphisms affect TPMT protein function and, as a
      result, therapeutic response to thiopurine drugs.

PMID- 15967991
TI  - Insights into regulation of human Schwann cell proliferation by Erk1/2 via a MEK
      independent and p56Lck-dependent pathway from leprosy bacilli.
AB  - Activation of extracellular signal-regulated kinase (Erk) 1/2, which plays a
      critical role in diverse cellular processes, including cell proliferation, is
      known to be mediated by the canonical Raf-mitogen-activated protein kinase kinase
      (MEK) kinase cascade. Alternative MEK-independent signaling pathways for Erk1/2
      activation in mammalian cells are not known. During our studies of human primary
      Schwann cell response to long-term infection of Mycobacterium leprae, the
      causative organism of leprosy, we identified that intracellular M. leprae
      activated Erk1/2 directly by lymphoid cell kinase (p56Lck), a Src family member,
      by means of a PKCepsilon-dependent and MEK-independent signaling pathway.
      Activation of this signaling induced nuclear accumulation of cyclin D1, G1/S
      phase progression, and continuous proliferation, but without transformation.
      Thus, our data reveal a previously unknown signaling mechanism of glial cell
      proliferation, which might play a role in dedifferentiation as well as nerve
      regeneration and degeneration. Our findings may also provide a potential
      mechanism by which an obligate intracellular bacterial pathogen like M. leprae
      subverts nervous system signaling to propagate its cellular niche for
      colonization and long-term bacterial survival.

PMID- 15967992
TI  - Genomic evolution of MHC class I region in primates.
AB  - To elucidate the origins of the MHC-B-MHC-C pair and the MHC class I chain
      related molecule (MIC)A-MICB pair, we sequenced an MHC class I genomic region of
      humans, chimpanzees, and rhesus monkeys and analyzed the regions from an
      evolutionary stand-point, focusing first on LINE sequences that are paralogous
      within each of the first two species and orthologous between them. Because all
      the long interspersed nuclear element (LINE) sequences were fragmented and
      nonfunctional, they were suitable for conducting phylogenetic study and, in
      particular, for estimating evolutionary time. Our study has revealed that MHC-B
      and MHC-C duplicated 22.3 million years (Myr) ago, and the ape MICA and MICB
      duplicated 14.1 Myr ago. We then estimated the divergence time of the rhesus
      monkey by using other orthologous LINE sequences in the class I regions of the
      three primate species. The result indicates that rhesus monkeys, and possibly the
      Old World monkeys in general, diverged from humans 27-30 Myr ago. Interestingly,
      rhesus monkeys were found to have not the pair of MHC-B and MHC-C but many
      repeated genes similar to MHC-B. These results support our inference that MHC-B
      and MHC-C duplicated after the divergence between apes and Old World monkeys.

PMID- 15967993
TI  - The bacterial chemotactic response reflects a compromise between transient and
      steady-state behavior.
AB  - Swimming bacteria detect chemical gradients by performing temporal comparisons of
      recent measurements of chemical concentration. These comparisons are described
      quantitatively by the chemotactic response function, which we expect to optimize
      chemotactic behavioral performance. We identify two independent chemotactic
      performance criteria: In the short run, a favorable response function should move
      bacteria up chemoattractant gradients; in the long run, bacteria should aggregate
      at peaks of chemoattractant concentration. Surprisingly, these two criteria
      conflict, so that when one performance criterion is most favorable, the other is
      unfavorable. Because both types of behavior are biologically relevant, we include
      both behaviors in a composite optimization that yields a response function that
      closely resembles experimental measurements. Our work suggests that the bacterial
      chemotactic response function can be derived from simple behavioral
      considerations and sheds light on how the response function contributes to
      chemotactic performance.

PMID- 15967994
TI  - Stress duration modulates the spatiotemporal patterns of spine formation in the
      basolateral amygdala.
AB  - It has long been hypothesized that morphological and numerical alterations in
      dendritic spines underlie long-term structural encoding of experiences. Here we
      investigate the efficacy of aversive experience in the form of acute
      immobilization stress (AIS) and chronic immobilization stress (CIS) in modulating
      spine density in the basolateral amygdala (BLA) of male rats. We find that CIS
      elicits a robust increase in spine density across primary and secondary branches
      of BLA spiny neurons. We observed this CIS-induced spinogenesis in the BLA 1 d
      after the termination of CIS. In contrast, AIS fails to affect spine density or
      dendritic arborization when measured 1 d later. Strikingly, the same AIS causes a
      gradual increase in spine density 10 d later but without any effect on dendritic
      arbors. Thus, by modulating the duration of immobilization stress, it is possible
      to induce the formation of new spines without remodeling dendrites. However,
      unlike CIS-induced spine formation, the gradual increase in spine density 10 d
      after a single exposure to AIS is localized on primary dendrites. Finally, this
      delayed induction of BLA spinogenesis is paralleled by a gradual development of
      anxiety-like behavior on the elevated plus-maze 10 d after AIS. These findings
      demonstrate that stressful experiences can lead to the formation of new dendritic
      spines in the BLA, which is believed to be a locus of storage for fear memories.
      Our results also suggest that stress may facilitate symptoms of chronic anxiety
      disorders like post-traumatic stress disorder by enhancing synaptic connectivity
      in the BLA.

PMID- 15967995
TI  - In search of an auditory engram.
AB  - Monkeys trained preoperatively on a task designed to assess auditory recognition
      memory were impaired after removal of either the rostral superior temporal gyrus
      or the medial temporal lobe but were unaffected by lesions of the rhinal cortex.
      Behavioral analysis indicated that this result occurred because the monkeys did
      not or could not use long-term auditory recognition, and so depended instead on
      short-term working memory, which is unaffected by rhinal lesions. The findings
      suggest that monkeys may be unable to place representations of auditory stimuli
      into a long-term store and thus question whether the monkey's cerebral memory
      mechanisms in audition are intrinsically different from those in other sensory
      modalities. Furthermore, it raises the possibility that language is unique to
      humans not only because it depends on speech but also because it requires long
      term auditory memory.

PMID- 15967996
TI  - Mammalian electrophysiology on a microfluidic platform.
AB  - The recent development of automated patch clamp technology has increased the
      throughput of electrophysiology but at the expense of visual access to the cells
      being studied. To improve visualization and the control of cell position, we have
      developed a simple alternative patch clamp technique based on microfluidic
      junctions between a main chamber and lateral recording capillaries, all
      fabricated by micromolding of polydimethylsiloxane (PDMS). PDMS substrates
      eliminate the need for vibration isolation and allow direct cell visualization
      and manipulation using standard microscopy. Microfluidic integration allows
      recording capillaries to be arrayed 20 microm apart, for a total chamber volume
      of <0.5 nl. The geometry of the recording capillaries permits high-quality,
      stable, whole-cell seals despite the hydrophobicity of the PDMS surface. Using
      this device, we are able to demonstrate reliable whole-cell recording of
      mammalian cells on an inexpensive microfluidic platform. Recordings of activation
      of the voltage-sensitive potassium channel Kv2.1 in mammalian cells compare well
      with traditional pipette recordings. The results make possible the integration of
      whole-cell electrophysiology with easily manufactured microfluidic lab-on-a-chip
      devices.

PMID- 15967997
TI  - Cell intrinsic alterations underlie hematopoietic stem cell aging.
AB  - Loss of immune function and an increased incidence of myeloid leukemia are two of
      the most clinically significant consequences of aging of the hematopoietic
      system. To better understand the mechanisms underlying hematopoietic aging, we
      evaluated the cell intrinsic functional and molecular properties of highly
      purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We
      found that LT-HSC aging was accompanied by cell autonomous changes, including
      increased stem cell self-renewal, differential capacity to generate committed
      myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression
      profiling revealed that LT-HSC aging was accompanied by the systemic down
      regulation of genes mediating lymphoid specification and function and up
      regulation of genes involved in specifying myeloid fate and function. Moreover,
      LT-HSCs from old mice expressed elevated levels of many genes involved in
      leukemic transformation. These data support a model in which age-dependent
      alterations in gene expression at the stem cell level presage downstream
      developmental potential and thereby contribute to age-dependent immune decline,
      and perhaps also to the increased incidence of leukemia in the elderly.

PMID- 15967998
TI  - Structure of bacterial tubulin BtubA/B: evidence for horizontal gene transfer.
AB  - alphabeta-Tubulin heterodimers, from which the microtubules of the cytoskeleton
      are built, have a complex chaperone-dependent folding pathway. They are thought
      to be unique to eukaryotes, whereas the homologue FtsZ can be found in bacteria.
      The exceptions are BtubA and BtubB from Prosthecobacter, which have higher
      sequence homology to eukaryotic tubulin than to FtsZ. Here we show that some of
      their properties are different from tubulin, such as weak dimerization and
      chaperone-independent folding. However, their structure is strikingly similar to
      tubulin including surface loops, and BtubA/B form tubulin-like protofilaments.
      Presumably, BtubA/B were transferred from a eukaryotic cell by horizontal gene
      transfer because their high degree of similarity to eukaryotic genes is unique
      within the Prosthecobacter genome.

PMID- 15967999
TI  - Substantial DNA damage from submicromolar intracellular hydrogen peroxide
      detected in Hpx- mutants of Escherichia coli.
AB  - Since the discovery of catalase, it has been postulated that aerobic organisms
      generate enough oxidants to threaten their own fitness and, in particular, their
      genetic stability. An alternative is that these enzymes exist to defend the cell
      against more-abundant oxidants imposed by external sources. These hypotheses were
      tested directly through study of Hpx- (katG katE ahpCF) mutants of Escherichia
      coli, which lack enzymes to scavenge hydrogen peroxide (H2O2). These strains grew
      well in anaerobic medium but poorly when they were aerated. The Hpx- bacteria
      formed filaments and exhibited high rates of mutagenesis, both indicators of DNA
      damage. An additional recA mutation caused Hpx- cells to die rapidly upon
      aeration, even though the intracellular H2O2 was <1 microM. Spin-trap experiments
      detected substantial hydroxyl radicals, and cell-permeable iron chelators
      eliminated both the phenotypic defects and hydroxyl-radical formation, confirming
      that the Fenton reaction was responsible. An Hpx- oxyR strain exhibited even more
      DNA lesions than did the Hpx- mutant, indicating that the OxyR stress response
      induced protein(s) that suppressed DNA damage. One critical protein was Dps, an
      iron-sequestration protein, because Hpx- dps mutants exhibited sensitivity
      similar to that of the Hpx- oxyR mutant. These results reveal that aerobic E.
      coli generates sufficient H2O2 to create toxic levels of DNA damage. Scavenging
      enzymes and controls on free iron are required to avoid that fate. The rate
      constant of the Fenton reaction measured at physiological pH was much higher than
      under the acidic conditions that were used to determine the commonly cited value.

PMID- 15968000
TI  - S1P3 receptor-induced reorganization of epithelial tight junctions compromises
      lung barrier integrity and is potentiated by TNF.
AB  - Pulmonary pathologies including adult respiratory distress syndrome are
      characterized by disruption of pulmonary integrity and edema compromising
      respiratory function. Sphingosine 1-phosphate (S1P) is a lipid mediator
      synthesized and/or stored in mast cells, platelets, and epithelial cells, with
      production up-regulated by the proinflammatory cytokines IL-1 and TNF. S1P
      administration via the airways but not via the vasculature induces lung leakage.
      Using receptor-null mice, we show that S1P, acting on S1P3 receptor expressed on
      both type I and type II alveolar epithelial cells but not vascular endothelium,
      induces pulmonary edema by acute tight junction opening. WT but not S1P3-null
      mice showed disruption of pulmonary epithelial tight junctions and the appearance
      of paracellular gaps between epithelial cells by electron microscopy within 1 h
      of airways exposure to S1P. We further show by fluorescence microscopy that S1P
      induced rapid loss of ZO-1 reactivity, an essential component of the cytoplasmic
      plaque associated with tight junctions, as well as of the tetraspannin Claudin
      18, an integral membrane organizer of tight junctions. S1P shows synergistic
      activity with the proinflammatory cytokine TNF, showing both pulmonary edema and
      mortality at subthreshold S1P doses. Specifically, preexposure of mice to
      subthreshold doses of TNF, which alone induced no lung edema, exacerbated S1P
      induced edema and impaired survival. S1P, acting through S1P3, regulates
      epithelial integrity and acts additively with TNF in compromising respiratory
      barrier function. Because S1P3-null mice are resistant to S1P-induced pulmonary
      leakage, either alone or in the presence of TNF, S1P3 antagonism may be useful in
      protecting epithelial integrity in pulmonary disease.

PMID- 15968002
TI  - Another Piece of the MALT Lymphomas Jigsaw.

PMID- 15968001
TI  - The evolution of human anti-double-stranded DNA autoantibodies.
AB  - It has been proposed that the anti-double-stranded DNA (dsDNA) response in
      patients with systemic lupus erythematosus (SLE) is antigen driven and that DNA
      or nucleosomes select anti-DNA reactive, somatically mutated B cells. We have
      used site-directed mutagenesis to systematically revert the somatic mutations of
      two human anti-dsDNA antibodies from SLE patients to analyze the resulting
      changes in DNA binding as well as binding to other autoantigens. Our data
      demonstrate that high-affinity binding to dsDNA and nucleosomes is acquired by
      somatic replacement mutations in a stepwise manner. Reactivity to surface
      structures of apoptotic cells is acquired by the same somatic mutations that
      generate high-affinity dsDNA binding. Importantly, revertant antibodies with germ
      line V regions did not show any measurable DNA reactivity. We propose that anti
      DNA autoantibodies are generated from nonautoreactive B cells during a normal
      immune response. B cells may acquire autoreactivity de novo during the process of
      somatic hypermutation. Nucleosomes, if available in lupus patients because of
      defects in clearing of apoptotic debris, might subsequently positively select
      high affinity anti-DNA B cells.

PMID- 15968003
TI  - Regression of ocular adnexal lymphoma after Chlamydia psittaci-eradicating
      antibiotic therapy.
AB  - PURPOSE: Some infectious agents contributing to lymphomagenesis have been
      considered targets for new therapeutic strategies. Chlamydia psittaci DNA has
      been detected in 80% of ocular adnexal lymphomas. The present pilot study was
      carried out to assess whether C psittaci-eradicating antibiotic therapy is
      associated with tumor regression in ocular adnexal lymphomas. PATIENTS AND
      METHODS: Nine patients with C psittaci-positive marginal-zone B-cell lymphoma of
      the ocular adnexa at diagnosis or relapse were treated with doxycycline 100 mg,
      bid orally, for 3 weeks. The presence of C psittaci DNA in peripheral-blood
      mononuclear cells (PBMCs) was also assessed before and after treatment in seven
      patients. Objective lymphoma regression was assessed 1, 3, and 6 months after
      therapy conclusion and every 6 months during follow-up. RESULTS: All patients
      completed antibiotic therapy with excellent tolerability. At 1 month from
      doxycycline assumption, chlamydial DNA was no longer detectable in PBMCs of all
      four positive patients. Objective response was complete in two patients, partial
      response (> 50%) was observed in two patients, and minimal response (< 50%) was
      observed in three patients. Duration of response in the seven responders was 12+,
      29+, 31+, 8+, 7+, 2+, and 1+ months, respectively. CONCLUSION: C psittaci
      eradicating antibiotic therapy with doxycycline is followed by objective response
      in patients with ocular adnexal lymphoma, even after multiple relapses of the
      disease. A confirmatory, large, phase II trial is warranted to confirm whether
      this fast, cheap, and well-tolerated therapy could replace other more aggressive
      strategies as first-line treatment against ocular adnexal lymphomas.

PMID- 15968004
TI  - Proteomic analysis of protein expression and oxidative modification in r6/2
      transgenic mice: a model of Huntington disease.
AB  - Huntington disease (HD) is a hereditary neurodegenerative disorder characterized
      by motor, psychiatric, and cognitive symptoms. The genetic defect responsible for
      the onset of the disease, expansion of CAG repeats in exon 1 of the gene that
      codes for huntingtin on chromosome 4, has been unambiguously identified. On the
      other hand, the mechanisms by which the mutation causes the disease are not
      completely understood yet. However, defects in energy metabolism of affected
      cells may cause oxidative damage, which has been proposed as one of the
      underlying molecular mechanisms that participate in the etiology of the disease.
      In our effort to investigate the extent of oxidative damage occurring at the
      protein level, we used a parallel proteomic approach to identify proteins
      potentially involved in processes upstream or downstream of the disease-causing
      huntingtin in a well established HD mouse model (R6/2 transgenic mice). We have
      demonstrated that the expression levels of dihydrolipoamide S-succinyltransferase
      and aspartate aminotransferase increase consistently over the course of disease
      (10-week-old mice). In contrast, pyruvate dehydrogenase expression levels were
      found to be decreased in 10-week-old HD transgenic mice compared with young (4
      week-old) mice. Our experimental approach also led to the identification of
      oxidatively modified proteins. Six proteins were found to be significantly
      oxidized in old R6/2 transgenic mice compared with either young transgenic mice
      or non-transgenic mice. These proteins are alpha-enolase, gamma-enolase (neuron
      specific enolase), aconitase, the voltage-dependent anion channel 1, heat shock
      protein 90, and creatine kinase. Because oxidative damage has proved to play an
      important role in the pathogenesis and the progression of Huntington disease, our
      results for the first time identify specific oxidatively modified proteins that
      potentially contribute to the pathogenesis of Huntington disease.

PMID- 15968005
TI  - Report of specific cardiovascular outcomes of the ADVANTAGE trial.

PMID- 15968006
TI  - Summaries for patients. Hormone replacement therapy does not increase severe
      lupus flares.

PMID- 15968007
TI  - Summaries for patients. What is the natural course of idiopathic pulmonary
      fibrosis?

PMID- 15968008
TI  - Summaries for patients. Using electrocardiography to detect problems with cardiac
      resynchronization devices.

PMID- 15968009
TI  - The effect of combined estrogen and progesterone hormone replacement therapy on
      disease activity in systemic lupus erythematosus: a randomized trial.
AB  - BACKGROUND: There is concern that exogenous female hormones may worsen disease
      activity in women with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate
      the effect of hormone replacement therapy (HRT) on disease activity in
      postmenopausal women with SLE. DESIGN: Randomized, double-blind, placebo
      controlled noninferiority trial conducted from March 1996 to June 2002. SETTING:
      16 university-affiliated rheumatology clinics or practices in 11 U.S. states.
      PATIENTS: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or
      stable-active (18.5%) SLE. INTERVENTIONS: 12 months of treatment with active drug
      (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12
      days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group
      and 87% for the placebo group. MEASUREMENTS: The primary end point was occurrence
      of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus,
      National Assessment-Systemic Lupus Erythematosus Disease Activity Index
      composite. RESULTS: Severe flare was rare in both treatment groups: The 12-month
      severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group,
      yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1
      sided 95% CI for the treatment difference was 0.078, within the prespecified
      margin of 9% for noninferiority. Mild to moderate flares were significantly
      increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person
      year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of
      flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P =
      0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous
      thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo
      group, 1 patient developed deep venous thrombosis. LIMITATIONS: Findings are not
      generalizable to women with high-titer anticardiolipin antibodies, lupus
      anticoagulant, or previous thrombosis. CONCLUSIONS: Adding a short course of HRT
      is associated with a small risk for increasing the natural flare rate of lupus.
      Most of these flares are mild to moderate. The benefits of HRT can be balanced
      against the risk for flare because HRT did not significantly increase the risk
      for severe flare compared with placebo.

PMID- 15968011
TI  - An electrocardiogram-based algorithm to detect loss of left ventricular capture
      during cardiac resynchronization therapy.
AB  - BACKGROUND: Loss of left ventricular capture in patients with cardiac
      resynchronization devices may account for worsening heart failure and can be
      difficult to diagnose without a programmer. OBJECTIVE: To determine whether
      distinct morphologic changes on the surface electrocardiogram indicate loss of
      left ventricular capture. DESIGN: After analysis of the R-S spike ratio in the 12
      lead electrocardiogram during right ventricular and biventricular pacing in 10
      patients, an algorithm to detect loss of left ventricular capture was developed.
      SETTING: University hospital. PATIENTS: 54 patients with a cardiac
      resynchronization device and underlying left bundle-branch block. MEASUREMENTS:
      Leads V1 and I of a 12-lead electrocardiogram were assessed after biventricular
      pacing was confirmed and after the device was programmed to right ventricular
      pacing only (simulating loss of left ventricular capture). RESULTS: The
      sensitivity of the algorithm to correctly identify loss of left ventricular
      capture was 94% (95% CI, 88.2% to 97.7%), and the specificity was 93% (CI, 86.3%
      to 95.8%). The likelihood ratio of a positive test result was 12.8 (CI, 6.443 to
      23.310), and the likelihood ratio of a negative test result was 0.06 (CI, 0.024
      to 0.137). LIMITATIONS: The algorithm was tested in patients in whom the right
      ventricular electrode was placed in the apex of the right ventricle only.
      CONCLUSION: Presence of biventricular capture--the prerequisite for successful
      cardiac resynchronization therapy--and loss of left ventricular capture can be
      accurately detected by an algorithm based on analysis of the R-S ratio on leads
      V1 and I of the surface electrocardiogram.

PMID- 15968010
TI  - The clinical course of patients with idiopathic pulmonary fibrosis.
AB  - BACKGROUND: Prospective data defining the clinical course in idiopathic pulmonary
      fibrosis (IPF) are sparse. OBJECTIVE: To analyze the clinical course of patients
      with mild to moderate IPF. DESIGN: Analysis of data from the placebo group of a
      randomized, controlled trial evaluating interferon-gamma1b. SETTING: Academic and
      community medical centers. PATIENTS: 168 patients in the placebo group of a trial
      evaluating interferon-gamma1b. MEASUREMENTS: Measures of physiology and dyspnea
      assessed at 12-week intervals; hospitalizations; and the pace of deterioration
      and cause of death over a median period of 76 weeks. RESULTS: Physiologic
      variables changed minimally during the study. However, 23% of patients required
      hospitalization for a respiratory disorder and 21% died. Idiopathic pulmonary
      fibrosis was the primary cause of death in 89% of patients who died, and an
      apparent acute clinical deterioration preceded death in 47% of these patients.
      LIMITATIONS: The instrument used to define the pace of deterioration and cause of
      death was applied retrospectively. CONCLUSIONS: Recognition of the common
      occurrence of acute fatal deterioration in patients with mild to moderate IPF has
      important implications for monitoring patients and supports early referral for
      lung transplantation.

PMID- 15968012
TI  - Independent medical examinations: an expanding source of physician liability.
AB  - Employers frequently ask physicians to conduct medical examinations and review
      radiology films and other diagnostic tests of employees. Physicians also provide
      such services at the request of other third parties. These examinations are
      commonly called independent medical examinations. Increasingly, patients are
      bringing and prevailing in medical malpractice lawsuits against physicians who
      conduct independent medical examinations, in part because of physicians'
      misconceptions of their legal duties in this context. Despite the absence of a
      traditional physician-patient relationship, physicians who conduct independent
      medical examinations still owe various legal duties to the examinee patient,
      although the precise scope of those duties is a source of constant debate and
      change. Since 2001 alone, 4 state supreme courts have exercised their discretion
      to hear cases on this issue, bearing witness to its medical, legal, and social
      significance. Given the current medical malpractice climate, it is imperative
      that physicians understand the potential liability inherent in conducting
      independent medical examinations. This article summarizes controlling law,
      clarifying an otherwise muddied legal picture. It also offers practical
      suggestions for limiting physician liability in independent medical examinations.

PMID- 15968013
TI  - Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients.
AB  - BACKGROUND: Bacterial infections are a major cause of illness and death in
      patients who are neutropenic after chemotherapy treatment for cancer. Trials have
      shown the efficacy of antibiotic prophylaxis in decreasing the incidence of
      bacterial infections but not in reducing mortality rates. PURPOSE: To evaluate
      whether antibiotic prophylaxis in neutropenic patients reduces mortality and
      incidence of infection and to assess related adverse events. DATA SOURCES: The
      Cochrane Cancer Network register of trials (2004), The Cochrane Library (Issue 4,
      2004), EMBASE (1980-2004), MEDLINE (1966-2004), and references of identified
      studies. STUDY SELECTION: Randomized, controlled trials comparing antibiotic
      prophylaxis with placebo or no intervention or another antibiotic in afebrile
      neutropenic patients. DATA EXTRACTION: Two reviewers independently appraised the
      quality of trials and extracted data. DATA SYNTHESIS: Ninety-five trials
      performed between 1973 and 2004 met inclusion criteria. Fifty-two trials
      addressed quinolone prophylaxis. Antibiotic prophylaxis significantly decreased
      the risk for death when compared with placebo or no treatment (relative risk,
      0.67 [95% CI, 0.55 to 0.81]). All prophylactic antibiotics were associated with
      an increased risk for adverse events (relative risk, 1.69 [CI, 1.14 to 2.50]).
      Fluoroquinolone prophylaxis reduced the risk for all-cause mortality (relative
      risk, 0.52 [CI, 0.35 to 0.77]), as well as infection-related mortality, fever,
      clinically documented infections, and microbiologically documented infections.
      Fluoroquinolone prophylaxis increased the risk for harboring bacilli resistant to
      the specific drug after treatment and adverse events, but these results were not
      statistically significant (relative risks, 1.69 [CI, 0.73 to 3.92]) and 1.30 [CI,
      0.61 to 2.76], respectively). LIMITATIONS: Most trials involved patients with
      hematologic cancer. Data on all-cause mortality were missing in 10 of 50 trials
      comparing prophylaxis with no prophylaxis. Effect estimates were larger in trials
      of unclear methodologic quality compared with trials of adequate methodologic
      quality. CONCLUSIONS: Antibiotic prophylaxis for neutropenic patients undergoing
      cytotoxic therapy reduces mortality. Mortality was substantially reduced when
      analysis was limited to fluoroquinolones. Antibiotic prophylaxis, preferably with
      a fluoroquinolone, should be considered for neutropenic patients.

PMID- 15968014
TI  - High and rising health care costs. Part 3: the role of health care providers.
AB  - One commonly held explanation for high and rising health care costs in the United
      States points to the market power of health care providers. This third article of
      a 4-part series examines how the prices and quantities of health care services
      interact to influence health care expenditures. The article also reviews cost
      containment strategies that are designed to reduce prices and quantities of
      services. One major difference between the costs of care in the United States and
      those in other developed nations is the price per unit of care--physician fees,
      payments per hospital day, and pharmaceutical prices. Greater quantities of high
      priced innovative technologies in the United States also contribute to higher
      expenditures in the United States compared with other nations. During the 1990s,
      payers were partially successful in slowing cost growth by reducing the prices of
      physician and hospital payments, but more recently, hospitals increased their
      market power by consolidation and could demand higher prices. Quantities and
      costs of services for Medicare beneficiaries vary markedly among geographic
      regions, with research showing an association between health care costs and the
      supply of hospital beds and specialist physicians. These findings suggest that
      limiting the supply of resources may reduce the quantity, and thereby the costs,
      of health services. Shifting the financial risk of health care costs from
      insurers to providers, as has been done with the Medicare diagnosis-related-group
      payment and capitation reimbursement, can also be effective in containing costs.

PMID- 15968015
TI  - National Institutes of Health State-of-the-Science Conference statement:
      management of menopause-related symptoms.

PMID- 15968016
TI  - Help for menopausal patients with lupus?

PMID- 15968018
TI  - Reviews: making sense of an often tangled skein of evidence.

PMID- 15968019
TI  - One in three.

PMID- 15968020
TI  - Commercial weight loss programs.

PMID- 15968021
TI  - Patient self-management of oral anticoagulation.

PMID- 15968022
TI  - Aggressive treatment of high-density lipoprotein cholesterol.

PMID- 15968023
TI  - A new concept of unopposed beta-adrenergic overstimulation in a patient with
      pheochromocytoma.

PMID- 15968024
TI  - Cognitive psychology of missed diagnoses.

PMID- 15968025
TI  - Liver cancer on the rise.

PMID- 15968027
TI  - Better information for better health care: the Evidence-based Practice Center
      program and the Agency for Healthcare Research and Quality.
AB  - To provide decision makers with the best available evidence, the Agency for
      Healthcare Research and Quality established a network of Evidence-based Practice
      Centers across North America. The centers perform systematic reviews on important
      questions posed by partner organizations about clinical, organizational, and
      policy interventions in healthcare. The Agency works closely with partners and
      other decision maker s to help translate that evidence into practice or policy.
      In this paper, we review important lessons we have learned over the past 7 years
      about how to increase the efficiency and impact of systematic reviews. Lessons
      concern selecting the right topics and scope, working effectively with partners,
      and balancing consistency and flexibility in methods. We examine continuing
      evolutions of the program and the impact of planned work on comparative
      effectiveness performed as part of the Medicare Modernization Act of 2003.

PMID- 15968028
TI  - Challenges in systematic reviews of complementary and alternative medicine
      topics.
AB  - The use of complementary and alternative medicine (CAM) continues to grow in the
      United States. The Agency for Healthcare Research and Quality has devoted a
      substantial proportion of the Evidence-based Practice Center (EPC) program to
      systematic reviews of CAM. Such syntheses present different challenges from those
      conducted on western medicine topics, and in many ways are more difficult. We
      discuss 3 challenges: identifying evidence about CAM, assessing the quality of
      individual studies, and addressing rare serious adverse events. We use
      illustrations from EPC evidence reports to show readers approaches to the 3 areas
      and then present specific recommendations for each issue.

PMID- 15968029
TI  - Challenges in systematic reviews of diagnostic technologies.
AB  - Diagnostic tests are critical components of effective health care. They help
      determine treatments that are most beneficial for a given patient. Their
      assessment is a complex process that includes such challenges as a dearth of
      studies that evaluate clinical outcomes and lack of data on use of the test in
      realistic clinical settings. The methodologic quality of studies of diagnostic
      tests also lags behind the quality of studies of therapeutic interventions.
      Statistical methods to combine diagnostic accuracy data are more complex and not
      as well developed, leading to difficulties in the interpretation of results. The
      Agency for Healthcare Research and Quality Technology Assessment Program has
      adopted a 6-level framework for evaluating diagnostic technologies. The model
      emphasizes the need for systematic reviews of diagnostic test studies to go
      beyond the assessment of technical feasibility and accuracy to examine the impact
      of the test on health outcomes. In this paper, we use examples from 3 Evidence
      based Practice Center reports to illustrate 3 challenges reviewers may face when
      reviewing diagnostic test literature: finding relevant studies, assessing
      methodologic quality of diagnostic accuracy studies, and synthesizing studies
      that evaluate tests in different patient populations or use different outcomes.

PMID- 15968030
TI  - Challenges in systematic reviews: synthesis of topics related to the delivery,
      organization, and financing of health care.
AB  - Some important health policy topics, such as those related to the delivery,
      organization, and financing of health care, present substantial challenges to
      established methods for evidence synthesis. For example, such reviews may ask:
      What is the effect of for-profit versus not-for-profit delivery of care on
      patient outcomes? Or, which strategies are the most effective for promoting
      preventive care? This paper describes innovative methods for synthesizing
      evidence related to the delivery, organization, and financing of health care. We
      found 13 systematic reviews on these topics that described novel methodologic
      approaches. Several of these syntheses used 3 approaches: conceptual frameworks
      to inform problem formulation, systematic searches that included nontraditional
      literature sources, and hybrid synthesis methods that included simulations to
      address key gaps in the literature. As the primary literature on these topics
      expands, so will opportunities to develop additional novel methods for performing
      high-quality comprehensive syntheses.

PMID- 15968031
TI  - Challenges in systematic reviews that evaluate drug efficacy or effectiveness.
AB  - Increasingly, consumers, clinicians, regulatory bodies, and insurers are using
      systematic reviews of drug interventions to select treatments and set policies.
      Although a systematic review cannot provide all the information a clinician needs
      to make an informed choice for therapy, it can help decision makers distinguish
      what claims about effectiveness are based on evidence, identify critical
      information gaps, describe features of the evidence that limit applicability in
      practice, and address whether drug effectiveness differs for particular subgroups
      of patients. To improve the relevance and validity of reviews of drug therapies,
      reviewers need to delineate clinically important subgroups, specific aims of
      therapy, and most important outcomes. They may need to find unpublished trials,
      studies other than direct comparator (head-to-head) trials, and additional
      details of published trials from pharmaceutical manufacturers and regulatory
      agencies. In this paper, we address ways to formulate questions relevant to
      specific clinical therapeutic aims; discuss types of studies to include in drug
      efficacy and effectiveness reviews and how to find them; and describe ways to
      assess applicability of studies to actual practice.

PMID- 15968032
TI  - Challenges in systematic reviews of economic analyses.
AB  - Economic analyses can provide valuable information for health care decision
      makers. Systematic reviews of economic analyses can integrate information from
      multiple studies and provide important insights by systematically examining how
      differences between models lead to different results. We use our experience in
      developing and implementing systematic reviews of economic analyses for the U.S.
      Preventive Services T ask Force, particularly our systematic review of the cost
      effectiveness of colorectal cancer screening, to illustrate key methodologic
      challenges and suggest a framework for other researchers in this area.

PMID- 15968033
TI  - Challenges in systematic reviews of educational intervention studies.
AB  - Educators have recognized the need to apply evidence-based approaches to medical
      training. To do so, medical educators must have access to reliable evidence on
      the impact of educational interventions. This paper describes 5 methodologic
      challenges to performing systematic reviews of educational interventions for
      health care professionals: finding reports of medical education interventions,
      assessing quality of study designs, assessing the scope of interventions,
      assessing the evaluation of interventions, and synthesizing the results of
      educational interventions. We offer suggestions for addressing these challenges
      and make recommendations for reporting, reviewing, and appraising interventions
      in medical education.

PMID- 15968034
TI  - Challenges in systematic reviews that assess treatment harms.
AB  - An evidence synthesis of a medical intervention should assess the balance of
      benefits and harms. Investigators performing systematic reviews of harms face
      challenges in finding data, rating the quality of harms reporting, and
      synthesizing and displaying data from different sources. Systematic reviews of
      harms often rely primarily on published clinical trials. Identifying important
      harms of treatment and quantifying the risk associated with them, however, often
      require a broader range of data sources, including unpublished trials,
      observational studies, and unpublished information on published trials submitted
      to the U.S. Food and Drug Administration. Each source of data has some potential
      for yielding important information. Criteria for judging the quality of harms
      assessment and reporting are still in their early stages of development.
      Investigators conducting systematic reviews of harms should consider empirically
      validating the criteria they use to judge the validity of studies reporting
      harms. Synthesizing harms data from different sources requires careful
      consideration of internal validity, applicability, and sources of heterogeneity.
      This article highlights examples of approaches to methodologic issues associated
      with performing systematic reviews of harms from 96 Evidence-based Practice
      Center evidence reports.

PMID- 15968035
TI  - Challenges in systematic reviews of therapeutic devices and procedures.
AB  - The authors discuss 3 challenges in conducting and interpreting any systematic
      review that are particularly relevant for systematic reviews of therapeutic
      devices or surgical procedures: 1) inclusion or exclusion of grey literature, 2)
      the role of nonrandomized studies, and 3) issues in applying the results to
      clinical care that are unique to the surgical and therapeutic device literature.
      The authors also discuss empirical evidence related to these topics and
      illustrate how reviewers in the Agency for Healthcare Research and Quality's
      Evidence-based Practice Center program have dealt with these challenges in
      developing evidence reports for decision makers and clinicians about therapeutic
      devices or surgical procedures.

PMID- 15968036
TI  - Challenges in using nonrandomized studies in systematic reviews of treatment
      interventions.
AB  - Randomized, controlled trials (RCTs) are firmly established as the standard for
      determining which medical treatments are effective. In some areas of health care,
      however, among them surgery, public health, and the organization of health care
      delivery, most evidence addressing the effectiveness of clinical or policy
      interventions rests on nonrandomized studies. We examine the use of study designs
      other than RCTs in Evidence-based Practice Center reports addressing questions of
      the effectiveness of treatment interventions. These reports offer the opportunity
      to examine the approaches used and the challenges faced by reviewers when
      nonrandomized studies are included and their quality assessed. We then offer
      recommendations for using these studies in systematic reviews of treatment
      interventions.

PMID- 15968037
TI  - Dissemination of Evidence-based Practice Center reports.
AB  - The Evidence-based Practice Center (EPC) program within the Agency for Healthcare
      Research and Quality (AHRQ) provides detailed evidence reports for partner
      organizations that they can translate into activities that improve patient care.
      A review of these dissemination activities provides a rich opportunity to
      understand how to create more successful linkages between best evidence and best
      practice. On the basis of interviews with EPC directors, AHRQ staff, and
      representatives of public and private users of EPC reports, we summarize the
      variety of efforts to disseminate the work of the EPCs. We also identify a case
      example of a successful dissemination of an EPC report. Experience to date
      reinforces the importance of creating close ties between researchers and the
      policymakers, clinicians, and other decision makers who use EPC evidence reports;
      developing a conceptual framework to guide the process; and establishing the
      resource foundation for the entire effort.

PMID- 15968038
TI  - Facultative methanotrophs revisited.

PMID- 15968039
TI  - Mechanisms of protein export across the bacterial outer membrane.

PMID- 15968040
TI  - Characterization of the replication region of plasmid pLS32 from the Natto strain
      of Bacillus subtilis.
AB  - Plasmid pL32 from the Natto strain of Bacillus subtilis belongs to a group of low
      copy-number plasmids in gram-positive bacteria that replicate via a theta
      mechanism of replication. We studied the DNA region encoding the replication
      protein, RepN, of pLS32, and obtained the following results. Transcription of the
      repN gene starts 167 nucleotides upstream from the translational start site of
      repN. The copy number of repN-coding plasmid pHDCS2, in which the repN gene was
      placed downstream of the IPTG (isopropyl-1-thio-beta-D-galactopyranoside)
      inducible Pspac promoter, was increased 100 fold by the addition of IPTG.
      Histidine-tagged RepN bound to a specific region in the repN gene containing five
      22-bp tandem repeats (iterons) with partial mismatches, as shown by gel
      retardation and foot printing analyses. Sequence alterations in the first three
      iterons resulted in an increase in plasmid copy number, whereas those in either
      the forth or fifth iteron resulted in the failure of plasmid replication. The
      iterons expressed various degrees of incompatibility with an incoming repN-driven
      replicon pSEQ243, with the first three showing the strongest incompatibility.
      Finally, by using a plasmid, pHDMAEC21, carrying the sequence alterations in all
      the five iterons in repN and thus unable to replicate but encoding intact RepN,
      the region necessary for replication was confined to a 96-bp sequence spanning
      the 3'-terminal half of the fourth iteron to an A+T-rich region located
      downstream of the fifth iteron. From these results, we conclude that the iterons
      in repN are involved in both the control of plasmid copy number and
      incompatibility, and we suggest that the binding of RepN to the last two iterons
      triggers replication by melting the A+T-rich DNA sequence.

PMID- 15968043
TI  - Acetobacter aceti possesses a proton motive force-dependent efflux system for
      acetic acid.
AB  - Acetic acid bacteria are obligate aerobes able to oxidize ethanol, sugar
      alcohols, and sugars into their corresponding acids. Among them, Acetobacter and
      Gluconacetobacter species have very high ethanol oxidation capacity, leading to
      accumulation of vast amounts of acetic acid outside the cell. Since these
      bacteria are able to grow in media with high concentrations of acetic acid, they
      must possess a specific mechanism such as an efflux pump by which they can resist
      the toxic effects of acetic acid. In this study, the efflux pump of Acetobacter
      aceti IFO 3283 was examined using intact cells and membrane vesicles. The
      accumulation of acetic acid/acetate in intact cells was increased by the addition
      of a proton uncoupler and/or cyanide, suggesting the presence of an energy
      dependent efflux system. To confirm this, right-side-out and inside-out membrane
      vesicles were prepared from A. aceti IFO 3283, and the accumulation of acetic
      acid/acetate in the vesicles was examined. Upon the addition of a respiratory
      substrate, the accumulation of acetic acid/acetate in the right-side-out vesicles
      was largely decreased, while its accumulation was very much increased in the
      inside-out vesicles. These respiration-dependent phenomena observed in both types
      of membrane vesicles were all sensitive to a proton uncoupler. Acetic
      acid/acetate uptake in the inside-out membrane vesicles was dependent not on ATP
      but on the proton motive force. Furthermore, uptake was shown to be rather
      specific for acetic acid and to be pH dependent, because higher uptake was
      observed at lower pH. Thus, A. aceti IFO 3283 possesses a proton motive force
      dependent efflux pump for acetic acid.

PMID- 15968042
TI  - Choline-binding protein D (CbpD) in Streptococcus pneumoniae is essential for
      competence-induced cell lysis.
AB  - Streptococcus pneumoniae is an important human pathogen that is able to take up
      naked DNA from the environment by a quorum-sensing-regulated process called
      natural genetic transformation. This property enables members of this bacterial
      species to efficiently acquire new properties that may increase their ability to
      survive and multiply in the human host. We have previously reported that
      induction of the competent state in a liquid culture of Streptococcus pneumoniae
      triggers lysis of a subfraction of the bacterial population resulting in release
      of DNA. We have also proposed that such competence-induced DNA release is an
      integral part of natural genetic transformation that has evolved to increase the
      efficiency of gene transfer between pneumococci. In the present work, we have
      further elucidated the mechanism behind competence-induced cell lysis by
      identifying a putative murein hydrolase, choline-binding protein D (CbpD), as a
      key component of this process. By using real-time PCR to estimate the amount of
      extracellular DNA in competent relative to noncompetent cultures, we were able to
      show that competence-induced cell lysis and DNA release are strongly attenuated
      in a cbpD mutant. Ectopic expression of CbpD in the presence or absence of other
      competence proteins revealed that CbpD is essentially unable to cause cell lysis
      on its own but depends on at least one additional protein expressed during
      competence.

PMID- 15968041
TI  - Calcium-induced virulence factors associated with the extracellular matrix of
      mucoid Pseudomonas aeruginosa biofilms.
AB  - Pseudomonas aeruginosa colonizes the pulmonary tissue of patients with cystic
      fibrosis (CF), leading to biofilm-associated infections. The pulmonary fluid of
      CF patients usually contains elevated concentrations of cations and may contain
      the P. aeruginosa redox-active pigment pyocyanin, which is known to disrupt
      calcium homeostasis of host cells. Since divalent cations are important bridging
      ions for bacterial polysaccharides and since they may play regulatory roles in
      bacterial gene expression, we investigated the effect of calcium ions on the
      extracellular matrix constituents of P. aeruginosa biofilms. For mucoid strain P.
      aeruginosa FRD1, calcium addition (1.0 and 10 mM as CaCl(2)) resulted in biofilms
      that were at least 10-fold thicker than biofilms without added calcium. Scanning
      confocal laser microscopy showed increased spacing between cells for the thick
      biofilms, and Fourier transform infrared spectroscopy revealed that the material
      between cells is primarily alginate. An algD transcriptional reporter
      demonstrated that calcium addition caused an eightfold increase in alg gene
      expression in FRD1 biofilms. Calcium addition also resulted in increased amounts
      of three extracellular proteases (AprA, LasB, and PrpL). Immunoblots of the
      biofilm extracellular material established that AprA was harbored within the
      biofilm extracellular matrix. An aprA deletion mutation and a mutation in gene
      for a putative P. aeruginosa calmodulin-like protein did not significantly affect
      calcium-induced biofilm structure. Two-dimensional gel electrophoresis showed
      increased amounts of phenazine biosynthetic proteins in FRD1 biofilms and in
      calcium-amended planktonic cultures. Spectrochemical analyses showed that the
      calcium addition causes a three- to fivefold increase in pyocyanin production.
      These results demonstrate that calcium addition affects the structure and
      extracellular matrix composition of mucoid P. aeruginosa biofilms, through
      increased expression and stability of bacterial extracellular products. The
      calcium-induced extracellular matrix of mucoid P. aeruginosa consists primarily
      of the virulence factor alginate and also harbors extracellular proteases and
      perhaps pyocyanin, a biomolecule that may further disrupt cellular calcium
      levels.

PMID- 15968044
TI  - Synergistic regulation of competence development in Bacillus subtilis by two Rap
      Phr systems.
AB  - The 11 Rap proteins of Bacillus subtilis comprise a conserved family of
      tetratricopeptide (TPR)-containing regulatory proteins. Their activity is
      inhibited by specific Phr pentapeptides produced from the product of phr genes
      through an export-import maturation process. We found that one of the proteins,
      namely RapF, is involved in the regulation of competence to DNA transformation.
      The ComA response regulator and transcription factor for initiation of competence
      development is the target of RapF. Specific binding of RapF to the carboxy
      terminal DNA-binding domain of ComA inhibits the response regulator's ability to
      bind its target DNA promoters. The PhrF C-terminal pentapeptide, QRGMI, inhibits
      RapF activity. The activity of RapF and PhrF in regulating competence development
      is analogous to the previously described activity of RapC and PhrC (L. J. Core
      and M. Perego, Mol. Microbiol. 49:1509-1522, 2003). In fact, the RapF and PhrF
      pair of proteins acts synergistically with RapC and PhrC in the overall
      regulation of the ComA transcription factor. Since the transcription of the RapC-
      and RapF-encoding genes is positively regulated by their own target ComA, an
      autoregulatory circuit must exist for the competence transcription factor in
      order to modulate its activity.

PMID- 15968045
TI  - Homocysteine toxicity in Escherichia coli is caused by a perturbation of branched
      chain amino acid biosynthesis.
AB  - In Escherichia coli the sulfur-containing amino acid homocysteine (Hcy) is the
      last intermediate on the methionine biosynthetic pathway. Supplementation of a
      glucose-based minimal medium with Hcy at concentrations greater than 0.2 mM
      causes the growth of E. coli Frag1 to be inhibited. Supplementation of Hcy
      treated cultures with combinations of branched-chain amino acids containing
      isoleucine or with isoleucine alone reversed the inhibitory effects of Hcy on
      growth. The last intermediate of the isoleucine biosynthetic pathway, alpha-keto
      beta-methylvalerate, could also alleviate the growth inhibition caused by Hcy.
      Analysis of amino acid pools in Hcy-treated cells revealed that alanine, valine,
      and glutamate levels are depleted. Isoleucine could reverse the effects of Hcy on
      the cytoplasmic pools of valine and alanine. Supplementation of the culture
      medium with alanine gave partial relief from the inhibitory effects of Hcy.
      Enzyme assays revealed that the first step of the isoleucine biosynthetic
      pathway, catalyzed by threonine deaminase, was sensitive to inhibition by Hcy.
      The gene encoding threonine deaminase, ilvA, was found to be transcribed at
      higher levels in the presence of Hcy. Overexpression of the ilvA gene from a
      plasmid could overcome Hcy-mediated growth inhibition. Together, these data
      indicate that in E. coli Hcy toxicity is caused by a perturbation of branched
      chain amino acid biosynthesis that is caused, at least in part, by the inhibition
      of threonine deaminase.

PMID- 15968046
TI  - Regulation of Pseudomonas quinolone signal synthesis in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that causes chronic lung
      infections in cystic fibrosis patients and is a major source of nosocomial
      infections. This bacterium controls many virulence factors by using two quorum
      sensing systems, las and rhl. The las system is composed of the LasR regulator
      protein and its cell-to-cell signal, N-(3-oxododecanoyl) homoserine lactone, and
      the rhl system is composed of RhlR and the signal N-butyryl homoserine lactone. A
      third intercellular signal, the Pseudomonas quinolone signal (PQS; 2-heptyl-3
      hydroxy-4-quinolone), also regulates numerous virulence factors. PQS synthesis
      requires the expression of multiple operons, one of which is pqsABCDE. Previous
      experiments showed that the transcription of this operon, and therefore PQS
      production, is negatively regulated by the rhl quorum-sensing system and
      positively regulated by the las quorum-sensing system and PqsR (also known as
      MvfR), a LysR-type transcriptional regulator protein. With the use of DNA
      mobility shift assays and beta-galactosidase reporter fusions, we have studied
      the regulation of pqsR and its relationship to pqsA, lasR, and rhlR. We show that
      PqsR binds the promoter of pqsA and that this binding increases dramatically in
      the presence of PQS, implying that PQS acts as a coinducer for PqsR. We have also
      mapped the transcriptional start site for pqsR and found that the transcription
      of pqsR is positively regulated by lasR and negatively regulated by rhlR. These
      results suggest that a regulatory chain occurs where pqsR is under the control of
      LasR and RhlR and where PqsR in turn controls pqsABCDE, which is required for the
      production of PQS.

PMID- 15968047
TI  - Microarray analysis and motif detection reveal new targets of the Salmonella
      enterica serovar Typhimurium HilA regulatory protein, including hilA itself.
AB  - DNA regulatory motifs reflect the direct transcriptional interactions between
      regulators and their target genes and contain important information regarding
      transcriptional networks. In silico motif detection strategies search for DNA
      patterns that are present more frequently in a set of related sequences than in a
      set of unrelated sequences. Related sequences could be genes that are coexpressed
      and are therefore expected to share similar conserved regulatory motifs. We
      identified coexpressed genes by carrying out microarray-based transcript
      profiling of Salmonella enterica serovar Typhimurium in response to the spent
      culture supernatant of the probiotic strain Lactobacillus rhamnosus GG.
      Probiotics are live microorganisms which, when administered in adequate amounts,
      confer a health benefit on the host. They are known to antagonize intestinal
      pathogens in vivo, including salmonellae. S. enterica serovar Typhimurium causes
      human gastroenteritis. Infection is initiated by entry of salmonellae into
      intestinal epithelial cells. The expression of invasion genes is tightly
      regulated by environmental conditions, as well as by many bacterial factors
      including the key regulator HilA. One mechanism by which probiotics may
      antagonize intestinal pathogens is by influencing invasion gene expression. Our
      microarray experiment yielded a cluster of coexpressed Salmonella genes that are
      predicted to be down-regulated by spent culture supernatant. This cluster was
      enriched for genes known to be HilA dependent. In silico motif detection revealed
      a motif that overlaps the previously described HilA box in the promoter region of
      three of these genes, spi4_H, sicA, and hilA. Site-directed mutagenesis, beta
      galactosidase reporter assays, and gel mobility shift experiments indicated that
      sicA expression requires HilA and that hilA is negatively autoregulated.

PMID- 15968048
TI  - DNA binding-uptake system: a link between cell-to-cell communication and biofilm
      formation.
AB  - DNA has recently been described as a major structural component of the
      extracellular matrix in biofilms. In streptococci, the competence-stimulating
      peptide (CSP) cell-to-cell signal is involved in competence for genetic
      transformation, biofilm formation, and autolysis. Among the genes regulated in
      response to the CSP are those involved in binding and uptake of extracellular
      DNA. We show in this study that a functional DNA binding-uptake system is
      involved in biofilm formation. A comGB mutant of Streptococcus mutans deficient
      in DNA binding and uptake, but unaffected in signaling, showed reduced biofilm
      formation. During growth in the presence of DNase I, biofilm was reduced in the
      wild type to levels similar to those found with the comGB mutant, suggesting that
      DNA plays an important role in the wild-type biofilm formation. We also showed
      that growth in the presence of synthetic CSP promoted significant release of DNA,
      with similar levels in the wild type and in the comGB mutant. The importance of
      the DNA binding-uptake system in biofilm formation points to possible novel
      targets to fight infections.

PMID- 15968049
TI  - The genomic island SGI1, containing the multiple antibiotic resistance region of
      Salmonella enterica serovar Typhimurium DT104 or variants of it, is widely
      distributed in other S. enterica serovars.
AB  - The global dissemination of the multiply-antibiotic-resistant Salmonella enterica
      serovar Typhimurium DT104 clone with the resistance genes located in a class 1
      integron, here designated In104, within genomic island SGI1 is a significant
      public health issue. Here, we have shown that SGI1 and variants of it carrying
      different combinations of resistance genes are found in several Salmonella
      enterica serovars. These are serovars Cerro, Derby, Dusseldorf, Infantis, Kiambu,
      and Paratyphi B dT(+) isolated from human infections and serovar Emek from sewage
      effluent. Two new variants, SGI1-I and SGI1-J, both of which include the dfrA1
      orfC cassette array, were identified.

PMID- 15968050
TI  - Coupling of NAD+ biosynthesis and nicotinamide ribosyl transport:
      characterization of NadR ribonucleotide kinase mutants of Haemophilus influenzae.
AB  - Previously, we characterized a pathway necessary for the processing of NAD+ and
      for uptake of nicotinamide riboside (NR) in Haemophilus influenzae. Here we
      report on the role of NadR, which is essential for NAD+ utilization in this
      organism. Different NadR variants with a deleted ribonucleotide kinase domain or
      with a single amino acid change were characterized in vitro and in vivo with
      respect to cell viability, ribonucleotide kinase activity, and NR transport. The
      ribonucleotide kinase mutants were viable only in a nadV+ (nicotinamide
      phosphoribosyltransferase) background, indicating that the ribonucleotide kinase
      domain is essential for cell viability in H. influenzae. Mutations located in the
      Walker A and B motifs and the LID region resulted in deficiencies in both NR
      phosphorylation and NR uptake. The ribonucleotide kinase function of NadR was
      found to be feedback controlled by NAD+ under in vitro conditions and by NAD+
      utilization in vivo. Taken together, our data demonstrate that the NR
      phosphorylation step is essential for both NR uptake across the inner membrane
      and NAD+ synthesis and is also involved in controlling the NAD+ biosynthesis
      rate.

PMID- 15968052
TI  - Binding of Pseudomonas aeruginosa AlgZ to sites upstream of the algZ promoter
      leads to repression of transcription.
AB  - Mucoid variants of the opportunistic pathogen Pseudomonas aeruginosa produce the
      exopolysaccharide alginate and colonize the respiratory tracts of cystic fibrosis
      patients. The genes encoding the alginate biosynthetic enzymes are clustered in a
      single operon, which is under tight transcriptional control. One essential
      activator of the alginate operon is AlgZ, a proposed ribbon-helix-helix DNA
      binding protein that shares 30% amino acid identity with the Mnt repressor of
      Salmonella enterica serovar Typhimurium bacteriophage P22. In the current study,
      we examined the role of AlgZ as an autoregulator. Using single-copy algZ-lacZ
      transcription fusions, an increase in algZ transcription was observed in an algZ
      mutant compared to the isogenic wild-type strain, suggesting that AlgZ may have
      an additional role as a repressor. To identify the AlgZ binding site, overlapping
      regions upstream of algZ were incubated with AlgZ and analyzed by electrophoretic
      mobility shift assays. Specific binding activity was localized to a region
      spanning from 66 to 185 base pairs upstream of the algZ transcriptional start
      site. Two AlgZ binding sites were defined using copper-phenanthroline
      footprinting and deletion analyses, with one site centered at 93 base pairs and
      the other centered at 161 base pairs upstream of the algZ promoter. Deletion of
      both binding sites resulted in the loss of AlgZ binding. These results indicate
      that AlgZ represses algZ transcription, and this activity is mediated by multiple
      AlgZ-DNA interactions.

PMID- 15968051
TI  - Functional analysis of the Burkholderia cenocepacia ZmpA metalloprotease.
AB  - Burkholderia cenocepacia ZmpA is expressed as a preproenzyme typical of
      thermolysin-like proteases such as Pseudomonas aeruginosa LasB and Bacillus
      thermoproteolyticus thermolysin. The zmpA gene was expressed using the pPRO-EXHTa
      His(6) tag expression system, which incorporates a six-His tag at the N-terminal
      end of the protein, and recombinant ZmpA was purified using Ni-nitrilotriacetic
      acid affinity chromatography. Upon refolding of the recombinant His(6)-pre-pro
      ZmpA (62 kDa), the fusion protein was autoproteolytically cleaved into 36-kDa
      (mature ZmpA) and 27-kDa peptides. Site-directed mutagenesis was employed to
      infer the identity of the active site residues of ZmpA and to confirm that the
      enzyme undergoes autoproteolytic cleavage. Oligonucleotide mutagenesis was used
      to replace H(465) with G(465) or A(465), E(377) with A(377) or D(377), or H(380)
      with P(380) or A(380). Mutagenesis of H(465), E(377), or H(380) resulted in the
      loss of both autocatalytic activity and proteolytic activity. ZmpA with either
      substitution in H(380) was not detectable in B. cenocepacia cell extracts. The
      activity of the recombinant ZmpA was inhibited by EDTA and 1,10 phenanthroline,
      indicating that it is a zinc metalloprotease. ZmpA, however, was not inhibited by
      phosphoramidon, a classical inhibitor of the thermolysin-like proteases. The
      refolded mature ZmpA enzyme was proteolytically active against various substrates
      including hide powder azure, type IV collagen, fibronectin, neutrophil alpha-1
      proteinase inhibitor, alpha(2)-macroglobulin, and gamma interferon, suggesting
      that B. cenocepacia ZmpA may cause direct tissue damage to the host or damage to
      host tissues through a modulation of the host's immune system.

PMID- 15968053
TI  - Glutamyl-tRNA reductase of Chlorobium vibrioforme is a dissociable homodimer that
      contains one tightly bound heme per subunit.
AB  - delta-Aminolevulinic acid, the biosynthetic precursor of tetrapyrroles, is
      synthesized from glutamate via the tRNA-dependent five-carbon pathway in the
      green sulfur bacterium Chlorobium vibrioforme. The enzyme glutamyl-tRNA reductase
      (GTR), encoded by the hemA gene, catalyzes the first committed step in this
      pathway, which is the reduction of tRNA-bound glutamate to produce glutamate 1
      semialdehyde. To characterize the GTR protein, the hemA gene from C. vibrioforme
      was cloned into expression plasmids that added an N-terminal His(6) tag to the
      expressed protein. The His-tagged GTR protein was purified using Ni affinity
      column chromatography. GTR was observable as a 49-kDa band on sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels. The native molecular
      mass, as determined by gel filtration chromatography, appeared to be
      approximately 40 kDa, indicating that native GTR is a monomer. However, when the
      protein was mixed with 5% (vol/vol) glycerol, the product had an apparent
      molecular mass of 95 kDa, indicating that the protein is a dimer under these
      conditions. Purified His(6)-GTR was catalytically active in vitro when it was
      incubated with Escherichia coli glutamyl-tRNA(Glu) and purified recombinant
      Chlamydomonas reinhardtii glutamate-1-semialdehyde aminotransferase. The
      expressed GTR contained 1 mol of tightly bound heme per mol of pep tide subunit.
      The heme remained bound to the protein throughout purification and was not
      removed by anion- or cation-exchange column chromatography. However, the bound
      heme was released during SDS-PAGE if the protein was denatured in the presence of
      beta-mercaptoethanol. Added heme did not inhibit the activity of purified
      expressed GTR in vitro. However, when the GTR was expressed in the presence of 3
      amino-2,3- dihydrobenzoic acid (gabaculine), an inhibitor of heme synthesis, the
      purified GTR had 60 to 70% less bound heme than control GTR, and it was inhibited
      by hemin in vitro.

PMID- 15968054
TI  - Transport and metabolism of citrate by Streptococcus mutans.
AB  - Streptococcus mutans, a normal inhabitant of dental plaque, is considered a
      primary etiological agent of dental caries. Two virulence determinants of S.
      mutans are its acidogenicity and aciduricity (the ability to produce acid and the
      ability to survive and grow at low pH, respectively). Citric acid is ubiquitous
      in nature; it is a component of fruit juices, bones, and teeth. In lactic acid
      bacteria citrate transport has been linked to increased survival in acidic
      conditions. We identified putative citrate transport and metabolism genes in S.
      mutans, which led us to investigate citrate transport and metabolism. Our goals
      in this study were to determine the mechanisms of citrate transport and
      metabolism in S. mutans and to examine whether citrate modulates S. mutans
      aciduricity. Radiolabeled citrate was used during citrate transport to identify
      citrate metal ion cofactors, and thin-layer chromatography was used to identify
      metabolic end products of citrate metabolism. S. mutans was grown in medium MM4
      with different citrate concentrations and pH values, and the effects on the
      growth rate and cell survival were monitored. Intracellular citrate inhibited the
      growth of the bacteria, especially at low pH. The most effective cofactor for
      citrate uptake by S. mutans was Fe(3+). The metabolic end product of citrate
      metabolism was aspartate, and a citrate transporter mutant was more citrate
      tolerant than the parent.

PMID- 15968055
TI  - Transposon mutagenesis in a marine synechococcus strain: isolation of swimming
      motility mutants.
AB  - Certain marine unicellular cyanobacteria of the genus Synechococcus exhibit a
      unique type of swimming motility characterized by the absence of flagella or any
      other obvious organelles of motility. While the abundant cell surface-associated
      130-kDa glycoprotein SwmA is known to be required for the generation of thrust,
      identification of other components of the motility apparatus has, until recently,
      been unsuccessful. Here we report on the development of a transposon mutagenesis
      system for use with marine Synechococcus sp. strain WH8102, a model organism for
      which the genome has been sequenced. Utilizing this mutagenesis technique, we
      have isolated 17 independent mutants impaired in swimming motility. These 17
      transposon insertions are located in nine open reading frames, which cluster in
      three separate regions of the genome. Included within these clusters are several
      multicomponent transport systems as well as a number of glycosyltransferases.

PMID- 15968056
TI  - Stable accumulation of sigma54 in Helicobacter pylori requires the novel protein
      HP0958.
AB  - Several flagellar genes in Helicobacter pylori are dependent on sigma(54) (RpoN)
      for their expression. These genes encode components of the basal body, the hook
      protein, and a minor flagellin, FlaB. A protein-protein interaction map for H.
      pylori constructed from a high-throughput screen of a yeast two-hybrid assay
      (http://pim.hybrigenics.com/pimriderext/common/) revealed interactions between
      sigma(54) and the conserved hypothetical protein HP0958. To see if HP0958
      influences sigma(54) function, the corresponding gene was disrupted with a
      kanamycin resistance gene (aphA3) in H. pylori ATCC 43504 and the resulting
      mutant was analyzed. The hp0958:aphA3 mutant was nonmotile and failed to produce
      flagella. Introduction of a functional copy of hp0958 into the genome of the
      hp0958:aphA3 mutant restored flagellar biogenesis and motility. The hp0958:aphA3
      mutant was deficient in expressing two sigma(54)-dependent reporter genes, flaB'
      'xylE and hp1120'-'xylE. Levels of sigma(54) in the hp0958 mutant were
      substantially lower than those in the parental strain, suggesting that the
      failure of the mutant to express the genes in the RpoN regulon and produce
      flagella was due to reduced sigma(54) levels. Expressing sigma(54) at high levels
      by putting rpoN under the control of the ureA promoter restored flagellar
      biogenesis and motility in the hp0958:aphA3 mutant. Turnover of sigma(54) was
      more rapid in the hp0958:aphA3 mutant than it was in the wild-type strain,
      suggesting that HP0958 supports wild-type sigma(54) levels in H. pylori by
      protecting it from proteolysis.

PMID- 15968057
TI  - Initiation and synthesis of the Streptococcus pneumoniae type 3 capsule on a
      phosphatidylglycerol membrane anchor.
AB  - The type 3 synthase from Streptococcus pneumoniae is a processive beta
      glycosyltransferase that assembles the type 3 polysaccharide [3)-beta-D-GlcUA-(1-
      >4)-beta-D-Glc-(1-->] by a multicatalytic process. Polymer synthesis occurs via
      alternate additions of Glc and GlcUA onto the nonreducing end of the growing
      polysaccharide chain. In the presence of a single nucleotide sugar substrate, the
      type 3 synthase ejects its nascent polymer and also adds a single sugar onto a
      lipid acceptor. Following single sugar incorporation from either UDP-[(14)C]Glc
      or UDP-[(14)C]GlcUA, we found that phospholipase D digestion of the Glc-labeled
      lipid yielded a product larger than a monosaccharide, while digestion of the
      GlcUA-labeled lipid resulted in a product larger than a disaccharide. These data
      indicated that the lipid acceptor contained a headgroup and that the order of
      addition to the lipid acceptor was Glc followed by GlcUA. Higher-molecular-weight
      product synthesized in vitro was also sensitive to phospholipase D digestion,
      suggesting that the same lipid acceptor was being used for single sugar additions
      and for polymer formation. Mass spectral analysis of the anionic lipids of a type
      3 S. pneumoniae strain demonstrated the presence of glycosylated
      phosphatidylglycerol. This lipid was also observed in Escherichia coli strains
      expressing the recombinant type 3 synthase. The presence of the lipid primer in
      S. pneumoniae membranes explained both the ability of the synthase to reinitiate
      polysaccharide synthesis following ejection of its nascent chain and the
      association of newly synthesized polymer with the membrane. Unlike most S.
      pneumoniae capsular polysaccharides, the type 3 capsule is not covalently linked
      to the cell wall. The present data indicate that phosphatidylglycerol may anchor
      the type 3 polysaccharide to the cell membrane.

PMID- 15968058
TI  - pyd genes of Rhizobium sp. strain TAL1145 are required for degradation of 3
      hydroxy-4-pyridone, an aromatic intermediate in mimosine metabolism.
AB  - Rhizobium sp. strain TAL1145 degrades the Leucaena toxin mimosine and its
      degradation product 3-hydroxy-4-pyridone (HP). The aim of this investigation is
      to characterize the Rhizobium genes for HP degradation and transport. These genes
      were localized by subcloning and mutagenesis on a previously isolated cosmid,
      pUHR263, containing mid genes of TAL1145 required for mimosine degradation. Two
      structural genes, pydA and pydB, encoding a metacleavage dioxygenase and a
      hydrolase, respectively, are required for degradation of HP, and three genes,
      pydC, pydD, and pydE, encoding proteins of an ABC transporter, are involved in
      the uptake of HP by TAL1145. These genes are induced by HP, although both pydA
      and pydB show low levels of expression without HP. pydA and pydB are
      cotranscribed, while pydC, pydD, and pydE are each transcribed from separate
      promoters. PydA and PydB show no homology with other dioxygenases and hydrolases
      in Sinorhizobium meliloti, Mesorhizobium loti, and Bradyrhizobium japonicum.
      Among various root nodule bacteria, the ability to degrade mimosine or HP is
      unique to some Leucaena-nodulating Rhizobium strains.

PMID- 15968059
TI  - Staphylococcus aureus ClpC is required for stress resistance, aconitase activity,
      growth recovery, and death.
AB  - The ability of Staphylococcus aureus to adapt to various conditions of stress is
      the result of a complex regulatory response. Previously, it has been demonstrated
      that Clp homologues are important for a variety of stress conditions, and our
      laboratory has shown that a clpC homologue was highly expressed in the S. aureus
      strain DSM20231 during biofilm formation relative to expression in planktonic
      cells. Persistence and long-term survival are a hallmark of biofilm-associated
      staphylococcal infections, as cure frequently fails even in the presence of
      bactericidal antimicrobials. To determine the role of clpC in this context, we
      performed metabolic, gene expression, and long-term growth and survival analyses
      of DSM20231 as well as an isogenic clpC allelic-replacement mutant, a sigB
      mutant, and a clpC sigB double mutant. As expected, the clpC mutant showed
      increased sensitivity to oxidative and heat stresses. Unanticipated, however, was
      the reduced expression of the tricarboxylic acid (TCA) cycle gene citB (encoding
      aconitase), resulting in the loss of aconitase activity and preventing the
      catabolization of acetate during the stationary phase. clpC inactivation
      abolished post-stationary-phase recovery but also resulted in significantly
      enhanced stationary-phase survival compared to that of the wild-type strain.
      These data demonstrate the critical role of the ClpC ATPase in regulating the TCA
      cycle and implicate ClpC as being important for recovery from the stationary
      phase and also for entering the death phase. Understanding the stationary- and
      post-stationary-phase recovery in S. aureus may have important clinical
      implications, as little is known about the mechanisms of long-term persistence of
      chronic S. aureus infections associated with formation of biofilms.

PMID- 15968060
TI  - Phenylacetate catabolism in Rhodococcus sp. strain RHA1: a central pathway for
      degradation of aromatic compounds.
AB  - In gram-negative bacteria, a pathway for aerobic degradation of phenylacetic acid
      (PAA) that proceeds via phenylacetyl-coenzyme A (CoA) and hydrolytic ring fission
      plays a central role in the degradation of a range of aromatic compounds. In
      contrast, the PAA pathway and its role are not well characterized in gram
      positive bacteria. A cluster including 13 paa genes encoding enzymes orthologous
      to those of gram-negative bacteria was identified on the chromosome of
      Rhodococcus sp. strain RHA1. These genes were transcribed during growth on PAA,
      with 11 of the genes apparently in an operon yielding a single transcript.
      Quantitative proteomic analyses revealed that at least 146 proteins were more
      than twice as abundant in PAA-grown cells of RHA1 than in pyruvate-grown cells.
      Of these proteins, 29 were identified, including 8 encoded by the paa genes.
      Knockout mutagenesis indicated that paaN, encoding a putative ring-opening
      enzyme, was essential for growth on PAA. However, paaF, encoding phenylacetyl-CoA
      ligase, and paaR, encoding a putative regulator, were not essential. paaN was
      also essential for growth of RHA1 on phenylacetaldehyde, phenylpyruvate, 4
      phenylbutyrate, 2-phenylethanol, 2-phenylethylamine, and l-phenylalanine. In
      contrast, growth on 3-hydroxyphenylacetate, ethylbenzene, and styrene was
      unaffected. These results suggest that the range of substrates degraded via the
      PAA pathway in RHA1 is somewhat limited relative to the range in previously
      characterized gram-negative bacteria.

PMID- 15968061
TI  - OmcF, a putative c-Type monoheme outer membrane cytochrome required for the
      expression of other outer membrane cytochromes in Geobacter sulfurreducens.
AB  - Outer membrane cytochromes are often proposed as likely agents for electron
      transfer to extracellular electron acceptors, such as Fe(III). The omcF gene in
      the dissimilatory Fe(III)-reducing microorganism Geobacter sulfurreducens is
      predicted to code for a small outer membrane monoheme c-type cytochrome. An OmcF
      deficient strain was constructed, and its ability to reduce and grow on Fe(III)
      citrate was found to be impaired. Following a prolonged lag phase (150 h), the
      OmcF-deficient strain developed the ability to grow in Fe(III) citrate medium
      with doubling times and yields that were ca. 145% and 70% of those of the wild
      type, respectively. Comparison of the c-type cytochrome contents of outer
      membrane-enriched fractions prepared from wild-type and OmcF-deficient cultures
      confirmed the outer membrane association of OmcF and revealed multiple changes in
      the cytochrome content of the OmcF-deficient strain. These changes included loss
      of expression of two previously characterized outer membrane cytochromes, OmcB
      and OmcC, and overexpression of a third previously characterized outer membrane
      cytochrome, OmcS, during growth on Fe(III) citrate. The omcB and omcC transcripts
      could not be detected in the OmcF-deficient mutant by either reverse
      transcriptase PCR or Northern blot analyses. Expression of the omcF gene in trans
      restored both the capacity of the OmcF-deficient mutant to reduce Fe(III) and
      wild-type levels of omcB and omcC mRNA and protein. Thus, elimination of OmcF may
      impair Fe(III) reduction by influencing expression of OmcB, which has previously
      been demonstrated to play a critical role in Fe(III) reduction.

PMID- 15968062
TI  - Mutational analysis of a bifunctional ferrisiderophore receptor and signal
      transducing protein from Pseudomonas aeruginosa.
AB  - The FpvA protein of Pseudomonas aeruginosa strain PAO1 mediates uptake of a
      siderophore, ferripyoverdine. It is also a component of a signal transduction
      pathway that controls production of an exotoxin, a protease, pyoverdine, and FpvA
      itself. The purpose of the research described here was to dissect these different
      functions of FpvA. Signaling involves an N-terminal domain of FpvA, and it was
      shown that this domain is probably located in the periplasm, as expected. Short
      peptides were inserted at 36 sites within FpvA by linker insertion mutagenesis.
      The effects of these mutations on the presence of FpvA in the outer membrane, on
      FpvA-mediated uptake of ferripyoverdine, and on pyoverdine synthesis and gene
      expression were determined. Five of the mutations resulted in the absence of FpvA
      from the outer membrane of the bacteria. All of the remaining mutations
      eliminated either the transport or signaling function of FpvA and most affected
      both functions. Three mutations prevented transport of ferripyoverdine but had no
      effect on the signal transduction pathway showing that transport of
      ferripyoverdine is not required for the trans-membrane signaling process.
      Conversely, eight mutations affected pyoverdine-mediated signaling but had no
      effect on transport of ferripyoverdine. These data show that insertions
      throughout FpvA resulted in loss of function and that signaling and transport are
      separate and discrete functions of FpvA.

PMID- 15968063
TI  - Assimilation of nicotinamide mononucleotide requires periplasmic AphA phosphatase
      in Salmonella enterica.
AB  - Salmonella enterica can obtain pyridine from exogenous nicotinamide
      mononucleotide (NMN) by three routes. In route 1, nicotinamide is removed from
      NMN in the periplasm and enters the cell as the free base. In route 2, described
      here, phosphate is removed from NMN in the periplasm by acid phosphatase (AphA),
      and the produced nicotinamide ribonucleoside (NmR) enters the cell via the PnuC
      transporter. Internal NmR is then converted back to NMN by the NmR kinase
      activity of NadR. Route 3 is seen only in pnuC* transporter mutants, which import
      NMN intact and can therefore grow on lower levels of NMN. Internal NMN produced
      by either route 2 or route 3 is deamidated to nicotinic acid mononucleotide and
      converted to NAD by the biosynthetic enzymes NadD and NadE.

PMID- 15968064
TI  - Llama antibodies against a lactococcal protein located at the tip of the phage
      tail prevent phage infection.
AB  - Bacteriophage p2 belongs to the most prevalent lactococcal phage group (936)
      responsible for considerable losses in industrial production of cheese.
      Immunization of a llama with bacteriophage p2 led to higher titers of
      neutralizing heavy-chain antibodies (i.e., devoid of light chains) than of the
      classical type of immunoglobulins. A panel of p2-specific single-domain antibody
      fragments was obtained using phage display technology, from which a group of
      potent neutralizing antibodies were identified. The antigen bound by these
      antibodies was identified as a protein with a molecular mass of 30 kDa,
      homologous to open reading frame 18 (ORF18) of phage sk1, another 936-like phage
      for which the complete genomic sequence is available. By the use of
      immunoelectron microscopy, the protein is located at the tip of the tail of the
      phage particle. The addition of purified ORF18 protein to a bacterial culture
      suppressed phage infection. This result and the inhibition of cell lysis by anti
      ORF18 protein antibodies support the conclusion that the ORF18 protein plays a
      crucial role in the interaction of bacteriophage p2 with the surface receptors of
      Lactococcus lactis.

PMID- 15968065
TI  - Transcriptional analysis of the conserved ftsZ gene cluster in Mycoplasma
      genitalium and Mycoplasma pneumoniae.
AB  - Several experimental approaches were used to construct a detailed transcriptional
      profile of the phylogenetically conserved ftsZ cell division gene cluster in both
      Mycoplasma genitalium and its closest relative, Mycoplasma pneumoniae. We
      determined initiation and termination points for the cluster, as well as an
      absolute steady-state RNA level for each gene. Transcription of this cluster in
      both these organisms was shown to be highly strand specific. While the four genes
      in this cluster are cotranscribed, their transcription unit also includes two
      genes of close proximity yet disparate function. A transcription initiation point
      immediately upstream of these two genes was detected in M. genitalium but not M.
      pneumoniae. In M. pneumoniae, transcription of the six genes terminates at a
      poly(U)-tailed hairpin. In M. genitalium, this transcription terminates at two
      closely spaced points by an unknown mechanism. Real-time reverse transcription
      PCR analysis of this cluster in M. pneumoniae shows that mRNA levels for all six
      genes vary at most fivefold and form a gradient of decreasing quantity with
      increasing distance from the promoter at the beginning of the cluster. mRNA from
      coding regions was approximately 20- to 100-fold more abundant than that from
      intergenic regions. We estimated the most abundant mRNA we detected at 0.6 copy
      per cell. We conclude that groups of functionally related genes in M. genitalium
      and M. pneumoniae are often preceded by promoters but rarely followed by
      terminators. This causes functionally unrelated genes to be commonly
      cotranscribed in these organisms.

PMID- 15968066
TI  - Characterization of six lipoproteins in the sigmaE regulon.
AB  - In Escherichia coli, sigma(E) regulon functions are required for envelope
      homeostasis during stress and are essential for viability under all growth
      conditions. The E. coli genome encodes approximately 100 lipoproteins, and 6 of
      these are regulated by sigma(E). Phenotypes associated with deletion of each of
      these lipoproteins are the subject of this report. One lipoprotein, YfiO, is
      essential for cellular viability. However, overexpression of this protein is not
      sufficient to alleviate the requirement of sigma(E) for viability, suggesting
      that the sigma(E) regulon provides more than one essential function. The
      remaining five lipoproteins in the sigma(E) regulon are nonessential; cells are
      viable even when all five are removed simultaneously. Deletion of three
      nonessential lipoprotein genes (nlpB, yraP, ygfL) results in the exhibition of
      phenotypes that suggest they are important for maintenance of the integrity of
      the cell envelope. deltanlpB cells are selectively sensitive to rifampin;
      deltayraP cells are selectively sensitive to sodium dodecyl sulfate. Such
      selective sensitivity has not been previously reported. Both deltayraP and
      deltanlpB are synthetically lethal with surA::Cm, which encodes a periplasmic
      chaperone and PPIase, suggesting that NlpB and YraP play roles in a periplasmic
      folding pathway that functions in parallel with that of SurA. Finally, the
      deltayfgL mutant exhibits a broad range of envelope defects, including
      sensitivity to several membrane-impermeable agents, an altered outer membrane
      protein profile, synthetic lethality with both surA::Cm and deltafkpA::Cm
      strains, and sensitivity to a bactericidal permeability-increasing peptide. We
      suggest that this lipoprotein performs a very important but as-yet-unknown
      function in maintaining the integrity of the cell envelope.

PMID- 15968067
TI  - Two new Sinorhizobium meliloti LysR-type transcriptional regulators required for
      nodulation.
AB  - The establishment of an effective nitrogen-fixing symbiosis between Sinorhizobium
      meliloti and its legume host alfalfa (Medicago sativa) depends on the timely
      expression of nodulation genes that are controlled by LysR-type regulators.
      Ninety putative genes coding for LysR-type transcriptional regulators were
      identified in the recently sequenced S. meliloti genome. All 90 putative lysR
      genes were mutagenized using plasmid insertions as a first step toward
      determining their roles in symbiosis. Two new LysR-type symbiosis regulator
      genes, lsrA and lsrB, were identified in the screening. Both the lsrA and lsrB
      genes are expressed in free-living S. meliloti cells, but they are not required
      for cell growth. An lsrA1 mutant was defective in symbiosis and elicited only
      white nodules that exhibited no nitrogenase activity. Cells of the lsrA1 mutant
      were recovered from the white nodules, suggesting that the lsrA1 mutant was
      blocked early in nodulation. An lsrB1 mutant was deficient in symbiosis and
      elicited a mixture of pink and white nodules on alfalfa plants. These plants
      exhibited lower overall nitrogenase activity than plants inoculated with the wild
      type strain, which is consistent with the fact that most of the alfalfa plants
      inoculated with the lsrB1 mutant were short and yellow. Cells of the lsrB1 mutant
      were recovered from both pink and white nodules, suggesting that lsrB1 mutants
      could be blocked at multiple points during nodulation. The identification of two
      new LysR-type symbiosis transcriptional regulators provides two new avenues for
      understanding the complex S. meliloti-alfalfa interactions which occur during
      symbiosis.

PMID- 15968068
TI  - Epimerase active domain of Pseudomonas aeruginosa AlgG, a protein that contains a
      right-handed beta-helix.
AB  - The polysaccharide alginate forms a protective capsule for Pseudomonas aeruginosa
      during chronic pulmonary infections. The structure of alginate, a linear polymer
      of beta1-4-linked O-acetylated d-mannuronate (M) and l-guluronate (G), is
      important for its activity as a virulence factor. Alginate structure is mediated
      by AlgG, a periplasmic C-5 mannuronan epimerase. AlgG also plays a role in
      protecting alginate from degradation by the periplasmic alginate lyase AlgL.
      Here, we show that the C-terminal region of AlgG contains a right-handed beta
      helix (RHbetaH) fold, characteristic of proteins with the carbohydrate-binding
      and sugar hydrolase (CASH) domain. When modeled based on pectate lyase C of
      Erwinia chrysanthemi, the RHbetaH of AlgG has a long shallow groove that may
      accommodate alginate, similar to protein/polysaccharide interactions of other
      CASH domain proteins. The shallow groove contains a 324-DPHD motif that is
      conserved among AlgG and the extracellular mannuronan epimerases of Azotobacter
      vinelandii. Point mutations in this motif disrupt mannuronan epimerase activity
      but have no effect on alginate secretion. The D324A mutation has a dominant
      negative phenotype, suggesting that the shallow groove in AlgG contains the
      catalytic face for epimerization. Other conserved motifs of the epimerases, 361
      NNRSYEN and 381-NLVAYN, are predicted to lie on the opposite side of the RHbetaH
      from the catalytic center. Point mutations N362A, N367A, and V383A result in
      proteins that do not protect alginate from AlgL, suggesting that these mutant
      proteins are not properly folded or not inserted into the alginate biosynthetic
      scaffold. These motifs are likely involved in asparagine and hydrophobic
      stacking, required for structural integrity of RHbetaH proteins, rather than for
      mannuronan catalysis. The results suggest that the AlgG RHbetaH protects alginate
      from degradation by AlgL by channeling the alginate polymer through the proposed
      alginate biosynthetic scaffold while epimerizing approximately every second d
      mannuronate residue to l-guluronate along the epimerase catalytic face.

PMID- 15968069
TI  - Host- and tissue-specific pathogenic traits of Staphylococcus aureus.
AB  - Comparative genomics were used to assess genetic differences between
      Staphylococcus aureus strains derived from infected animals versus colonized or
      infected humans. A total of 77 veterinary isolates were genetically characterized
      by high-throughput amplified fragment length polymorphism (AFLP). Bacterial
      genotypes were introduced in a large AFLP database containing similar information
      for 1,056 human S. aureus strains. All S. aureus strains isolated from animals in
      close contact with humans (e.g., pet animals) were predominantly classified in
      one of the five main clusters of the AFLP database (cluster I). In essence,
      mastitis-associated strains from animals were categorized separately (cluster
      IVa) and cosegregated with bacteremia-associated strains from humans.
      Distribution of only 2 out of 10 different virulence genes differed across the
      clusters. The gene encoding the toxic shock syndrome protein (tst) was more often
      encountered among veterinary strains (P < 0.0001) and even more in the mastitis
      related strains (P<0.0001) compared to human isolate results. The gene encoding
      the collagen binding protein (cna) was rarely detected among invasive human
      strains. The virulence potential, as indicated by the number of virulence genes
      per strain, did not differ significantly between the human- and animal-related
      strains. Our data show that invasive infections in pets and humans are usually
      due to S. aureus strains with the same genetic background. Mastitis-associated S.
      aureus isolated in diverse farm animal species form a distinct genetic cluster,
      characterized by an overrepresentation of the toxic shock syndrome toxin
      superantigen-encoding gene.

PMID- 15968070
TI  - Identification of a second collagen-like glycoprotein produced by Bacillus
      anthracis and demonstration of associated spore-specific sugars.
AB  - Certain carbohydrates (rhamnose, 3-O-methyl rhamnose, and galactosamine) have
      been demonstrated to be present in Bacillus anthracis spores but absent in
      vegetative cells. Others have demonstrated that these spore-specific sugars are
      constituents of the glycoprotein BclA. In the current work, spore extracts were
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A second
      collagen-like glycoprotein, BclB, was identified in B. anthracis. The protein
      moiety of this glycoprotein was identified by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MS) and the carbohydrate
      components by gas chromatography-mass spectrometry and tandem mass spectrometry.
      Spore-specific sugars were also demonstrated to be components of BclB.

PMID- 15968071
TI  - Genetic evidence that GTP is required for transposition of IS903 and Tn552 in
      Escherichia coli.
AB  - Surprisingly little is known about the role of host factors in regulating
      transposition, despite the potentially deleterious rearrangements caused by the
      movement of transposons. An extensive mutant screen was therefore conducted to
      identify Escherichia coli host factors that regulate transposition. An E. coli
      mutant library was screened using a papillation assay that allows detection of
      IS903 transposition events by the formation of blue papillae on a colony. Several
      host mutants were identified that exhibited a unique papillation pattern: a
      predominant ring of papillae just inside the edge of the colony, implying that
      transposition was triggered within these cells based on their spatial location
      within the colony. These mutants were found to be in pur genes, whose products
      are involved in the purine biosynthetic pathway. The transposition ring phenotype
      was also observed with Tn552, but not Tn10, establishing that this was not unique
      to IS903 and that it was not an artifact of the assay. Further genetic analyses
      of purine biosynthetic mutants indicated that the ring of transposition was
      consistent with a GTP requirement for IS903 and Tn552 transposition. Together,
      our observations suggest that transposition occurs during late stages of colony
      growth and that transposition occurs inside the colony edge in response to both a
      gradient of exogenous purines across the colony and the developmental stage of
      the cells.

PMID- 15968072
TI  - Analysis of gene islands involved in methanopterin-linked C1 transfer reactions
      reveals new functions and provides evolutionary insights.
AB  - In this study, the occurrence and chromosomal clustering of genes encoding C(1)
      transfer reactions linked to tetrahydromethanopterin (H(4)MPT) were analyzed in a
      variety of proteobacteria and in representatives of the Planctomycetes via
      genomic analysis or via partial sequencing by cosmid walking. Although a tendency
      for clustering was found common for the genes of interest, significant variations
      in gene order and the degree of clustering were uncovered both between and within
      different groups of Proteobacteria and between Proteobacteria and Planctomycetes.
      Phylogenetic analyses suggested that the evolution of genes encoding H(4)MPT
      linked reactions in Proteobacteria involved lateral transfers within
      Proteobacteria and possibly between Proteobacteria and other phyla. Gene cluster
      comparisons revealed a number of novel genes potentially involved in the C(1)
      transfer reactions, and these were analyzed by mutation and expression analyses.
      Four genes, a homolog of pabB, and three genes conserved between methanogenic
      Archaea and Bacteria possessing H(4)MPT-linked functions, orfY, orf1, and afpA
      were shown to be involved in formaldehyde oxidation/detoxification, as judged by
      specific mutant phenotypes. In particular, pabB contributes to the biosynthesis
      of para-aminobenzoic acid, a precursor of both tetrahydrofolate and H(4)MPT, and
      afpA apparently encodes a novel dihydromethanopterin reductase, based on mutant
      complementation experiments.

PMID- 15968073
TI  - Sialylation of group B streptococcal capsular polysaccharide is mediated by cpsK
      and is required for optimal capsule polymerization and expression.
AB  - Several bacterial pathogens have evolved the means to escape immune detection by
      mimicking host cell surface carbohydrates that are crucial for self/non-self
      recognition. Sialic acid, a terminal residue on these carbohydrates, inhibits
      activation of the alternate pathway of complement by recruiting the immune
      modulating molecule factors H, I, and iC3b. Sialylation of capsular
      polysaccharide (CPS) is important for virulence of group B streptococci (GBS), a
      significant human pathogen. We previously reported that cpsK, a gene within the
      cps locus of type III GBS, could complement a sialyltransferase deficient lst
      mutant of Haemophilus ducreyi, implicating its role in sialylation of the GBS
      capsule. To explore the function of cpsK in GBS capsule production, we created a
      mutant in cpsK. Immunoblot analysis and enzyme-linked immunosorbent assay using
      anti-type III CPS antisera demonstrated that the mutant CPS did not contain
      sialic acid. This was confirmed by high-performance liquid chromatography after
      mild acid hydrolysis of the CPS. Although increased CPS chain length was seen for
      this strain, CPS production was <20% of the parental isolate. An episomal cpsK
      copy restored synthesis of sialo-CPS to wild-type levels. These data support our
      hypothesis that cpsK encodes the GBS CPS sialyltransferase and provide further
      evidence that lack of CPS oligosaccharide sialylation reduces the amount of CPS
      expressed on the cell surface. These observations also imply that one or more of
      the components involved in synthesis or transport of oligosaccharide repeating
      units requires a sialo-oligosaccharide for complete activity.

PMID- 15968075
TI  - Activities of the Serratia marcescens heme receptor HasR and isolated plug and
      beta-barrel domains: the beta-barrel forms a heme-specific channel.
AB  - The Serratia marcescens hemophore-specific outer membrane receptor HasR is a
      member of the TonB-dependent family of autoregulated receptors. It can transport
      either heme itself or heme bound to the hemophore HasA. On the basis of sequence
      and functional similarities with other TonB-dependent outer membrane receptors
      whose three-dimensional structures have been determined, a HasR structure model
      was proposed. The mature HasR protein comprises a 99-residue amino-terminal
      extension necessary for hasR transcription, followed by a plug domain of 139
      amino acids and a beta-barrel domain inserted in the outer membrane, the lumen of
      which is closed by the plug. This model was used to generate hasR deletions
      encoding HasR proteins with the native signal peptides but lacking either the N
      terminal regulatory extension or encoding the plug or the beta-barrel alone. The
      protein lacking the N-terminal extension, HasR delta11-91, was incorporated in
      the outer membrane and was fully functional for active uptake of free and
      hemophore-bound heme. The HasR beta-barrel, delta11-192, was also incorporated in
      the outer membrane and bound the hemophore but expressed no active heme transport
      properties. The HasR plug remained in the periplasm. Coexpression of the plug and
      the beta-barrel allowed partial plug insertion in the outer membrane,
      demonstrating that these two HasR domains interact in vivo. The beta-barrel and
      the plug also interact in vitro. Nevertheless, the two domains did not complement
      each other to reconstitute an active TonB-dependent receptor for free or
      hemophore-bound heme uptake. Production of the beta-barrel alone selectively
      increased passive diffusion of heme but not of other exogenous compounds. A
      mutation at histidine 603, which is required for heme uptake through the wild
      type receptor, abolished heme diffusion, showing that HasR delta11-192 forms a
      specific heme channel.

PMID- 15968074
TI  - Genomic sequence of an otitis media isolate of nontypeable Haemophilus
      influenzae: comparative study with H. influenzae serotype d, strain KW20.
AB  - In 1995, the Institute for Genomic Research completed the genome sequence of a
      rough derivative of Haemophilus influenzae serotype d, strain KW20. Although
      extremely useful in understanding the basic biology of H. influenzae, these data
      have not provided significant insight into disease caused by nontypeable H.
      influenzae, as serotype d strains are not pathogens. In contrast, strains of
      nontypeable H. influenzae are the primary pathogens of chronic and recurrent
      otitis media in children. In addition, these organisms have an important role in
      acute otitis media in children as well as other respiratory diseases. Such
      strains must therefore contain a gene repertoire that differs from that of strain
      Rd. Elucidation of the differences between these genomes will thus provide
      insight into the pathogenic mechanisms of nontypeable H. influenzae. The genome
      of a representative nontypeable H. influenzae strain, 86-028NP, isolated from a
      patient with chronic otitis media was therefore sequenced and annotated. Despite
      large regions of synteny with the strain Rd genome, there are large
      rearrangements in strain 86-028NP's genome architecture relative to the strain Rd
      genome. A genomic island similar to an island originally identified in H.
      influenzae type b is present in the strain 86-028NP genome, while the mu-like
      phage present in the strain Rd genome is absent from the strain 86-028NP genome.
      Two hundred eighty open reading frames were identified in the strain 86-028NP
      genome that were absent from the strain Rd genome. These data provide new insight
      that complements and extends the ongoing analysis of nontypeable H. influenzae
      virulence determinants.

PMID- 15968076
TI  - Bacillus anthracis sortase A (SrtA) anchors LPXTG motif-containing surface
      proteins to the cell wall envelope.
AB  - Cell wall-anchored surface proteins of gram-positive pathogens play important
      roles during the establishment of many infectious diseases, but the contributions
      of surface proteins to the pathogenesis of anthrax have not yet been revealed.
      Cell wall anchoring in Staphylococcus aureus occurs by a transpeptidation
      mechanism requiring surface proteins with C-terminal sorting signals as well as
      sortase enzymes. The genome sequence of Bacillus anthracis encodes three sortase
      genes and eleven surface proteins with different types of cell wall sorting
      signals. Purified B. anthracis sortase A cleaved peptides encompassing LPXTG
      motif-type sorting signals between the threonine (T) and the glycine (G) residues
      in vitro. Sortase A activity could be inhibited by thiol-reactive reagents,
      similar to staphylococcal sortases. B. anthracis parent strain Sterne 34F(2), but
      not variants lacking the srtA gene, anchored the collagen-binding MSCRAMM
      (microbial surface components recognizing adhesive matrix molecules) BasC
      (BA5258/BAS4884) to the bacterial cell wall. These results suggest that B.
      anthracis SrtA anchors surface proteins bearing LPXTG motif sorting signals to
      the cell wall envelope of vegetative bacilli.

PMID- 15968077
TI  - Architecture and adhesive activity of the Haemophilus influenzae Hsf adhesin.
AB  - Haemophilus influenzae type b is an important cause of meningitis and other
      serious invasive diseases and initiates infection by colonizing the upper
      respiratory tract. Among the major adhesins in H. influenzae type b is a nonpilus
      protein called Hsf, a large protein that forms fiber-like structures on the
      bacterial surface and shares significant sequence similarity with the nontypeable
      H. influenzae Hia autotransporter. In the present study, we characterized the
      structure and adhesive activity of Hsf. Analysis of the predicted amino acid
      sequence of Hsf revealed three regions with high-level homology to the HiaBD1 and
      HiaBD2 binding domains in Hia. Based on examination of glutathione S-transferase
      fusion proteins corresponding to these regions, two of the three had adhesive
      activity and one was nonadhesive in assays with cultured epithelial cells.
      Structural modeling demonstrated that only the two regions with adhesive activity
      harbored an acidic binding pocket like the binding pocket identified in the
      crystal structure of HiaBD1. Consistent with these results, disruption of the
      acidic binding pockets in the adhesive regions eliminated adhesive activity.
      These studies advance our understanding of the architecture of Hsf and the family
      of trimeric autotransporters and provide insight into the structural determinants
      of H. influenzae type b adherence.

PMID- 15968078
TI  - Methylocella species are facultatively methanotrophic.
AB  - All aerobic methanotrophic bacteria described to date are unable to grow on
      substrates containing carbon-carbon bonds. Here we demonstrate that members of
      the recently discovered genus Methylocella are an exception to this. These
      bacteria are able to use as their sole energy source the one-carbon compounds
      methane and methanol, as well as the multicarbon compounds acetate, pyruvate,
      succinate, malate, and ethanol. To conclusively verify facultative growth,
      acetate and methane were used as model substrates in growth experiments with the
      type strain Methylocella silvestris BL2. Quantitative real-time PCR targeting the
      mmoX gene, which encodes a subunit of soluble methane monooxygenase, showed that
      copies of this gene increased in parallel with cell counts during growth on
      either acetate or methane as the sole substrate. This verified that cells
      possessing the genetic basis of methane oxidation grew on acetate as well as
      methane. Cloning of 16S rRNA genes and fluorescence in situ hybridization with
      strain-specific and genus-specific oligonucleotide probes detected no
      contaminants in cultures. The growth rate and carbon conversion efficiency were
      higher on acetate than on methane, and when both substrates were provided in
      excess, acetate was preferably used and methane oxidation was shut down. Our data
      demonstrate that not all methanotrophic bacteria are limited to growing on one
      carbon compounds. This could have major implications for understanding the
      factors controlling methane fluxes in the environment.

PMID- 15968079
TI  - Complete genome sequence and analysis of the multiresistant nosocomial pathogen
      Corynebacterium jeikeium K411, a lipid-requiring bacterium of the human skin
      flora.
AB  - Corynebacterium jeikeium is a "lipophilic" and multidrug-resistant bacterial
      species of the human skin flora that has been recognized with increasing
      frequency as a serious nosocomial pathogen. Here we report the genome sequence of
      the clinical isolate C. jeikeium K411, which was initially recovered from the
      axilla of a bone marrow transplant patient. The genome of C. jeikeium K411
      consists of a circular chromosome of 2,462,499 bp and the 14,323-bp bacteriocin
      producing plasmid pKW4. The chromosome of C. jeikeium K411 contains 2,104
      predicted coding sequences, 52% of which were considered to be orthologous with
      genes in the Corynebacterium glutamicum, Corynebacterium efficiens, and
      Corynebacterium diphtheriae genomes. These genes apparently represent the
      chromosomal backbone that is conserved between the four corynebacteria. Among the
      genes that lack an ortholog in the known corynebacterial genomes, many are
      located close to transposable elements or revealed an atypical G+C content,
      indicating that horizontal gene transfer played an important role in the
      acquisition of genes involved in iron and manganese homeostasis, in multidrug
      resistance, in bacterium-host interaction, and in virulence. Metabolic analyses
      of the genome sequence indicated that the "lipophilic" phenotype of C. jeikeium
      most likely originates from the absence of fatty acid synthase and thus
      represents a fatty acid auxotrophy. Accordingly, both the complete gene
      repertoire and the deduced lifestyle of C. jeikeium K411 largely reflect the
      strict dependence of growth on the presence of exogenous fatty acids. The
      predicted virulence factors of C. jeikeium K411 are apparently involved in
      ensuring the availability of exogenous fatty acids by damaging the host tissue.

PMID- 15968080
TI  - The Helicobacter pylori CrdRS two-component regulation system (HP1364/HP1365) is
      required for copper-mediated induction of the copper resistance determinant CrdA.
AB  - Here we describe that the Helicobacter pylori sensor kinase produced by HP1364
      and the response regulator produced by HP1365 and designated CrdS and CrdR,
      respectively, are both required for transcriptional induction of the H. pylori
      copper resistance determinant CrdA by copper ions. CrdRS-deficient mutants lacked
      copper induction of crdA expression and were copper sensitive. A direct role of
      CrdR in transcriptional regulation of crdA was confirmed by in vitro binding of
      CrdR to the crdA upstream region. A 21-nucleotide sequence located near the crdA
      promoter was shown to be required for CrdR binding.

PMID- 15968081
TI  - 2-PMPA, a NAAG peptidase inhibitor, attenuates magnetic resonance BOLD signals in
      brain of anesthetized mice: evidence of a link between neuron NAAG release and
      hyperemia.
AB  - N-acetylaspartylglutamate (NAAG), a dipeptide derivative of N-acetylaspartate
      (NAA) and glutamate (Glu), is present in neurons. Upon neurostimulation, NAAG is
      exported to astrocytes where it activates a specific metabotropic Glu surface
      receptor (mGluR3), and is then hydrolyzed by an astrocyte-specific enzyme, NAAG
      peptidase, liberating Glu, which can then be taken up by the astrocyte. NAAG is a
      selective mGluR3 agonist, one of several mGluRs that, when activated, triggers
      Ca2+ waves that spread to astrocytic endfeet in contact with the vascular system,
      where a secondary release of vasoactive agents induces a focal hyperemic response
      providing increased oxygen and nutrient availability to the stimulated neurons.
      Changes in blood oxygen levels can be assessed in vivo using a blood oxygenation
      level-dependent (BOLD) magnetic resonance imaging technique that reflects a
      paramagnetic effect of deoxyhemoglobin. In this study we used the competitive
      NAAG peptidase inhibitor 2-(phosphonomethyl) pentanedioic acid (2-PMPA) as a
      probe to interrupt the NAAG-mGluR3- Glu-astrocyte Ca2+ activation sequence. Using
      this probe, we investigated the relationship between release of the endogenous
      neuropeptide NAAG and brain blood oxygenation levels, as measured by changes in
      BOLD signals. In an anesthetized mouse, using an overtly nontoxic dose of 2-PMPA
      of 250 mg/kg i.p., there was an initial global BOLD signal increase of about 3%
      above control, lasting about 4 min, followed by a decrease from control of about
      4%, sustained over a 32.5-min period of the drug test procedure. Similar changes,
      but of reduced magnitude and duration, were observed at a dose of 167 mg/kg. The
      2-PMPA-induced decreases in BOLD signals appear to indicate that blood
      deoxyhemoglobin is elevated when endogenous NAAG cannot be hydrolyzed, thus
      linking the efflux of NAAG from neurons and its hydrolysis by astrocytes to
      hyperemic oxygenation responses in brain.

PMID- 15968082
TI  - Axotomy-induced early down-regulation of POU-IV class transcription factors Brn
      3a and Brn-3b in retinal ganglion cells.
AB  - It has been proposed that neurons being exposed to proapoptotic stimuli undergo
      dedifferentiation, a process that can either allow for regeneration and axon
      regrowth or, if remaining incomplete, can force the cell to activate apoptotic
      pathways. A pivotal step in the differentiation program from neuronal precursor
      cells to differentiated, postmitotic neurons is their exit from the cell cycle.
      The POU domain transcription factors Brn-3b and Brn-3a, which are expressed in
      retinal ganglion cells (RGCs) directly after the exit of RGC precursors from the
      cell cycle, can be employed as RGC-specific differentiation markers to study
      potential dedifferentiation of RGCs after axotomy. Here, we examined mRNAand
      protein expression of Brn-3a and -3b in rat RGCs following axonal lesion. We
      observed a rapid down-regulation of Brn-3a and -3b protein expression in
      axotomized RGCs, clearly preceding apoptosis of RGCs. Using real-time PCR, we
      show that regulation of Brn-3 expression occurred at the transcriptional level.
      The small subset of RGCs regenerating into a peripheral nerve graft did not (re
      )express Brn-3a or -b. In conclusion, we found further evidence supporting the
      hypothesis of a dedifferentiation process in severed mature neurons. As Brn-3b
      expression has been shown to be a prerequisite for developmental survival of most
      RGCs and Brn-3a activates transcription of anti-apoptotic genes, down-regulation
      of Brn-3 transcription factors might be causally involved in the secondary death
      of adult RGCs following axotomy.

PMID- 15968083
TI  - Oxidative stress activates transcription factor NF-kB-mediated protective
      signaling in primary rat neuronal cultures.
AB  - Activation of transcription factor nuclear factor-kappaB (NF-kappaB) can result
      in enhanced de novo synthesis of both proteins that confer protection and those
      that cause death. The present study was undertaken to clarify in primary neuronal
      cultures the consequences of the oxidative stress-induced activation of NF-kappaB
      and mediation of death or survival signals. The neuronal cultures were exposed to
      chemical ischemia (iodoacetic acid), followed by reperfusion (I/R insult). This
      insult injured the neurons, as manifested in a 7- to 10-fold increase in LDH
      release, and decreased the cellular content of IkappaBalpha by 55-65 %,
      indicating NF-kappaB activation. The antioxidants LY231617, melatonin, and sodium
      salicylate and the antioxidant and inhibitor of NF-kappaB activation pyrrolidine
      dithiocarbamate, protected the neurons against the insult and prevented the
      decrease in cellular IkappaBalpha content. In contrast, inhibition of NF-kappaB
      translocation by SN50 in both uninsulted and insulted neuronal cultures resulted
      in a 2.9- and 2.4-fold increase in LDH release, respectively. The results
      indicate that the insult-induced oxidative stress activates transcription factor
      NF-kappaB associated with induction of protection and suggest that constitutive
      activation of NF-kappaB under physiological conditions acts to protect the
      neurons against physiological injury.

PMID- 15968084
TI  - Postmortem parietal cortex TPH2 expression is not altered in schizophrenic,
      unipolar-depressed, and bipolar patients vs control subjects.
AB  - Serotonin (5-hydroxytryptamine [5-HT]) is a neurotransmitter synthesized in the
      raphe nuclei of the brain stem in the central nervous system (CNS) and also in
      the periphery. Dysfunction of the serotonergic system has been implicated in the
      pathogenesis of psychiatric disorders. Tryptophan hydroxylase (TPH) is the rate
      limiting enzyme in 5-HT biosynthesis. For more than a decade, only one gene
      encoding TPH was identified in vertebrates. Recently, a second TPH gene,
      designated TPH2, was detected, located on human chromosome 12, a susceptibility
      region for affective disorders. TPH2 is predominantly expressed in the brain,
      whereas the classical TPH gene, TPH1, is expressed in peripheral tissues. The
      discovery of the brain-abundant TPH2 gene justifies a new concept of the CNS
      serotonergic system. TPH2, rather than TPH1, has now become a candidate gene for
      5-HT-related affective disorders. We compared TPH2 mRNA levels in postmortem
      parietal cortex of unipolar-depressed, bipolar, and schizophrenic patients vs
      control subjects, using real-time reverse transcription polymerase chain
      reaction. No significant difference in TPH2 mRNA levels was found among the four
      diagnostic groups. The lack of difference might suggest that this gene is not
      involved in the etiology of of these psychiatric disorders. Alternatively, it is
      possible that the parietal cortex is not the relevant brain area involved in the
      pathophysiology of these disorders or that posttranscriptional modifications of
      TPH2 mRNA occur in these patients, causing changes in protein levels and/or
      enzymatic activity.

PMID- 15968085
TI  - Nicotine stimulates expression of the PNMT gene through a novel promoter
      sequence.
AB  - Transcription of the gene encoding the epinephrine-synthesizing enzyme
      phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28) accelerates in
      response to hormonal and neural stimuli. Cholinergic stimulation through neuronal
      nicotinic receptors constitutes the primary means for neural regulation of PNMT
      expression in the adrenal medulla (AM). Therefore, the regulatory sequence
      conveying responsiveness of the PNMT gene to nicotinic stimuli has been
      characterized in the 5' upstream region of the rat PNMT promoter. Functional
      analyses using nested deletion and substitution mutations of the PNMT promoter
      map the nicotine responsive region to a sequence spanning -633 to -595 bp,
      designated the PNMT nicotine-responsive element (NicRE). Sequences at the 5' (
      633 to -620) and 3' (-599 to -595) ends of this region are essential to convey
      nicotine responsiveness to PNMT promoter constructs expressed in primary bovine
      chromaffin cells and in selected lines derived from mouse pheochromocytomas and
      human neuroblastomas. Profiles of nuclear proteins associating with PNMT promoter
      sequences also change following nicotine treatment of these cells.
      Electrophoretic mobility shift and DNase I footprinting analyses distinguish
      multiple sites of DNA-protein interactions within the NicRE region. Because the
      PNMT promoter does not contain a cAMP responsive element (the site through which
      nicotine stimulation is mediated for other catecholamine-synthesizing and AM
      genes), the NicRE of the PNMT gene must therefore be distinct. Thus, nicotinic
      cholinergic stimuli appear to regulate expression of the epinephrine-synthesizing
      gene PNMT through a previously uncharacterized regulatory element.

PMID- 15968086
TI  - Neuregulins rescue PC12-ErbB-4 cells from cell death induced by beta-amyloid
      peptide: involvement of PI3K and PKC.
AB  - Neuregulins (NRGs), which are highly expressed in the nervous system, bind and
      activate two receptor tyrosine kinases, ErbB-3 and ErbB-4. We previously showed
      that NRG mediates survival of PC12-ErbB-4 cells from apoptosis induced by serum
      deprivation, tumor necrosis factor-alpha treatment, or H2O2. These effects of
      NRGs are mediated by the phosphoinositide 3-kinase (PI3K) signaling pathway. In
      the present study, we show that NRG induces a significant protective effect from
      beta-amyloid 25-35 (Abeta[25-35]) peptide-induced cell death. The PI3K signaling
      pathway might be involved in this effect of NRG as the downstream effector of
      PI3K, protein kinase B (PKB/AkT), is activated by NRG in the presence of Abeta,
      and PKB/AkT activation is inhibited by the PI3K inhibitor, LY294002. In addition,
      our results demonstrate that Abeta-induced cell death is reduced by expression of
      activated PI3K. These results suggest that PI3K-dependent pathways might regulate
      the toxic effect of Abeta. In addition, Abeta induced alteration in the levels of
      the proapoptotic protein Bax. Neuregulin (NRG) treatment however, induced
      elevation in the levels of the antiapoptotic protein BclxL. The NRG-mediated
      BclxL elevation is regulated by protein kinase C (PKC), as NRG failed to elevate
      BclxL in the presence of the PKC inhibitor, GF109203X. Moreover, activation of
      PKC by phorbol 12-myristate 13-acetate markedly attenuated cell death induced by
      Abeta and induced elevation in BclxL levels. The results suggest that NRG might
      affect cell viability using two signaling pathways: activation of PI3K/PKB/AkT
      pathway and activation of PKC, which results in increasing levels of the
      antiapoptotic protein BclxL.

PMID- 15968088
TI  - PACAP regulation of secretion and proliferation of pure populations of gastric
      ECL cells.
AB  - The gastric enterochromaffin-like (ECL) cell plays a major role in the regulation
      of gastric acid secretion. We have previously described that Pituitary Adenylate
      Cyclase-Activating Polypeptide (PACAP) is present on myenteric neurons in the rat
      and colocalizes with its high-affinity receptor, PAC1, expressed on the surface
      of gastric ECL cells. The study of ECL cell physiology has been hampered by the
      inability to isolate and purify ECL cells to homogeneity. Density gradient
      elutriation alone yields only 65-70% purity of ECL cells. In the present study,
      we used fluorescence-activated cell sorting (FACS) with a novel fluorescent
      ligand, Fluor-PACAP-38, for isolating pure ECL cells. FACS was used to isolate
      ECL cells based on their relatively small size, low density, and ability to bind
      the fluorescent ligand Fluor-PACAP-38. The sorted cells were unambiguously
      identified as ECL cells by immunohistochemical analysis using anti-PACAP type-I
      (PAC1), anti-histidine decarboxylase (HDC), and anti-somatostatin antibodies.
      Further confocal microscopy demonstrated that Fluor-PACAP-38, a ligand with a
      higher affinity for PAC1, bound to extracellular receptors of these FACS-purified
      cells. FACS yielded an average of 2 million ECL cells/4 rat stomachs, and >99% of
      the sorted cells were positive for PAC1 receptor and HDC expression. The absence
      of immunohistochemical staining for somatostatin indicated lack of contamination
      by gastric D cells, which are similar in size and shape to the ECL cells.
      Internalization of PACAP receptors and a rapid Ca2+ response in purified ECL
      cells were observed upon PACAP activation, suggesting that these cells are viable
      and biologically active. These ECL cells demonstrated a dose-dependent
      stimulation of proliferation in response to PACAP, with a maximum of 30%
      proliferation at a concentration of 10-7 M. Microarray studies were perfor med to
      confirm the expression of genes specific for ECL cells. These results demonstrate
      that rat gastric ECL cells can be isolated to homogeneity by using a combination
      of density gradient centrifugation, followed by cell sorting using Fluor-PACAP.
      These techniques now allow microarray studies to be performed in ECL cells to
      characterize their functional gene expression and will facilitate
      pharmacological, biochemical, and molecular studies on ECL cell function.

PMID- 15968087
TI  - Inhibition of multiple pathways accounts for the antiapoptotic effects of
      flavopiridol on potassium withdrawal-induced apoptosis in neurons.
AB  - Serum and potassium (S/K) deprivation is a well-known apoptotic model in
      cerebellar granule neurons (CGNs), used to study the efficacy of potential
      neuroprotective drugs. The objective of this study was to determine the pathways
      involved in the neuroprotective role of flavopiridol, a pan-inhibitor of cyclin
      dependent kinases (CDKs), upon S/K withdrawal-induced apoptosis in CGNs. Cell
      death in primary cultures of rat CGNs was accompanied by chromatin condensation
      and activation of caspases-3, -6, and -9. Caspase-3 activity was also evaluated
      by cleavage of 120-kDa alpha-spectrin. Flavopiridol (1 microM) prevented caspase
      activation and abolished apoptotic features mediated by S/K withdrawal. Re-entry
      in the cell cycle is also involved in apoptotic neuronal cell death. Flavopiridol
      (1 microM) inhibited DNA synthesis as measured by BrdU incorporation, thus
      enhancing proliferating cell nuclear antigen expression. Serum/potassium (S/K)
      deprivation induced apoptotic cell death mediated by the activation of several
      kinases such as glycogen synthase kinase-3beta and CDK5, as well as the breakdown
      of p35 in the neurotoxic fragment p25; inactivation of myocyte enhancer factor-2
      (MEF2) was also found. Pretreatment with flavopiridol prevented these biochemical
      and molecular alterations. Taken together, these findings suggest an apoptotic
      route in CGNs after S/K withdrawal mediated by the activation of several kinases
      involved in cell cycle deregulation and MEF2 inactivation. We propose that the
      antiapoptotic properties of flavopiridol are mediated through kinase pathway
      inhibition.

PMID- 15968089
TI  - Identification of two further splice variants of GABABR1 characterizes the
      conserved micro-exon 4 as a hot spot for regulated splicing in the rat brain.
AB  - Inhibitory neurotransmission in the mammalian brain is principally mediated by
      gamma-aminobutyric acid (GABA) acting through different subtypes of cell membrane
      GABA receptor (GABAR). The expression of one GABAR gene, GABABR1, is
      distinguished by the expression of multiple splice variants that encode different
      isoforms of the receptor. In the present study, we have identified two novel
      GABABR1 variants, GABABR1h (R1h) and GABABR1i (R1i), which appear to arise from
      alternative splicing of the GABABR1 gene. The expression of R1h and R1i is
      differentially regulated in brain and peripheral tissues, but expression is not
      altered in the brain of a genetic model of absence epilepsy (GAERS rat [genetic
      absence epilepsy rat from Strasbourg]). Both the R1h and R1i variants exhibit a
      novel 80-bp insert downstream of exon 4 that is flanked by consensus splice
      sites, and both encode C-terminal-truncated proteins. The new insight into the
      family of GABABR1 variants gained from this study identifies exon 4 as a
      preferred locus, or hot spot for regulated splicing in the GABABR1 gene. This
      finding correlates with the micro-exonic nature of exon 4 (21 bp). Bioinformatic
      analysis of micro-exon 4 and its flanking pre-mRNA sequences has revealed
      multiple, potentially competitive, exonic splicing enhancers that provide a
      mechanistic basis for the preponderance of alternative splicing events at this
      locus. Conservation of GABABR1 micro-exon 4 across species suggests a conserved
      functional role, facilitating either N-terminal protein production or post
      transcriptional gene regulation through regulated splicing coupled to transcript
      decay.

PMID- 15968090
TI  - Multiple myeloma: challenges and opportunities.

PMID- 15968092
TI  - Plasma cell labeling index.
AB  - Multiple myeloma is characterized by proliferation of monoclonal plasma cells
      (PCs), mostly in the bone marrow. The proliferative rate of the malignant plasma
      cell is an important determinant of the disease biology and can be measured as
      the percentage of PCs in the S-phase of the cell cycle. This percentage, or PC
      labeling index, can be measured using a slide-based immunofluorescence method
      using an antibody against 5-bromo-2'-deoxyuridine, which is actively incorporated
      by DNA of the dividing PCs. This technique, which can be performed using bone
      marrow or peripheral blood specimens, also utilizes concurrent cytoplasmic
      staining against immunoglobulin as well as kappa and lambda light chains.
      Employment of cytoplasmic immunoglobulin staining allows more specific
      identification of PCs as well as confirmation of the monoclonal nature of the PC
      population. The staining procedure, which can be done manually or using an
      automated stainer, as well as the process of reading and interpreting these
      slides is described in detail. The bone marrow peripheral blood labeling index is
      an important clinical test, providing valuable diagnostic and prognostic
      information.

PMID- 15968091
TI  - Immunophenotyping of plasma cells in multiple myeloma.
AB  - Multiparametric immunophenotyping of multiple myeloma (MM) and other plasma cell
      (PC) dyscrasias represents an attractive approach not only for research purposes
      but also in clinical practice. Based on well-established antigenic patterns,
      discrimination between myelomatous and normal PCs can be easily achieved in
      various types of samples, and this can be particularly valuable for the
      differential diagnosis between MGUS and MM and for monitoring residual disease in
      the latter. In addition, immunophenotyping may be an alternative and more
      reproducible method than morphology for evaluating PC infiltration, as well as
      for specifically analyzing DNA content and the cell-cycle distribution of
      different subsets of PCs. Despite the widespread use, standardization of methods
      and protocols still remains a challenge. In this chapter, we describe in detail
      the protocols and precise instructions for specimen collection, sample
      preparation, together with the methods for staining PCs and flow cytometry, data
      acquisition, and data analysis, including the more recent developments in the
      field. We highlight the most frequent limitations, and provide troubleshooting
      and practical recommendations that could help to solve them. The goal of this
      chapter is to emphasize the relevance of methodological issues in order to obtain
      reproducible and high-quality results regarding the phenotypic analysis of PCs.

PMID- 15968093
TI  - Conventional cytogenetics in myeloma.
AB  - Chromosome analysis has become an important diagnostic tool in the assessment of
      patients with multiple myeloma. Conventional cytogenetic analysis of myeloma
      cells is complicated by the difficulty in inducing myeloma cells to divide. A
      method for the culture and harvest of bone marrow samples from patients with
      myeloma is presented together with a protocol for producing G-banded metaphases
      for microscopic analysis. It is recommended that two or more cultures be
      established from each sample. There is extensive literature describing the use of
      various cocktails of mitogens to assist in obtaining dividing myeloma cells with
      little consensus as to the optimal method. A protocol is given for stimulating
      cells to divide using interleukin-4, the method in routine use in the Victorian
      Cancer Cytogenetics Service.

PMID- 15968094
TI  - Multicolor spectral karyotyping in multiple myeloma.
AB  - Multiple myeloma is a plasma cell disorder characterized at the cytogenetic level
      by aneuploid karyotypes with numerous complex structural aberrations.
      Unfortunately, conventional chromosome-banding techniques are unable to resolve
      many of these aberrations. Multicolor Spectral Karyotyping (SKY) is a molecular
      cytogenetic technique that utilizes chromosome-painting probes for characterizing
      complex structural chromosome aberrations. This innovative technology allows the
      simultaneous display of each of the 24 different chromosomes in a different
      color. Chromosomal sites of rearrangement or translocation between different
      chromosomes are visualized by a change in the color at the point of the
      aberration. The SKY technique makes possible the identification of chromosomal
      bands of unknown origin, including trans locations, insertions, complex
      rearrangements, and marker chromosomes, which, in many cases, go unresolved by
      traditional banding methods.

PMID- 15968095
TI  - Detection of chromosome 13 deletions by fluorescent in situ hybridization.
AB  - Multiple myeloma (MM), like other hematological malignancies, has both normal and
      clonal neoplastic cells coresiding in the bone marrow. To perform interphase
      fluorescent in situ hybridization (FISH) analysis accurately, for the detection
      of clonal chromosome abnormalities, it is crucial to restrict the analysis to the
      tumoral cells. The correct detection of these abnormalities may have diagnostic,
      prognostic, and therapeutic implications. Our laboratory has developed a clone
      specific cytoplasmic immunoglobulin (cIg) staining method coupled with FISH (cIg
      FISH) for the study of plasma cell (PC) neoplasms. An unlimited combination of
      DNA probes can be used with this technique to examine the genetic changes that
      frequently occur in patients with these diseases, one of which is abnormalities
      of chromosome 13. Using the two techniques simultaneously (i.e., cIg-FISH), we
      have demonstrated that approx 50% of patients with MM have abnormalities of
      chromosome 13, mostly monosomy, and when present involving the majority of the
      cells. In this chapter, we present the technical methodology for detecting
      chromosome abnormalities and how to restrict the analysis to the clonal PCs.

PMID- 15968096
TI  - Comparative genomic hybridization for analysis of changes in DNA copy number in
      multiple myeloma.
AB  - Multiple myeloma (MM) is a clonal neoplasm of terminally differentiated plasma
      cells (PCs). Conventional cytogenetic analysis is one of the widely accepted DNA
      genome-screening tools for identification of chromosomal aberrations in MM. The
      success rate of detection of abnormal karyotypes by conventional cytogenetic
      analysis in myeloma is very low because of the low mitotic activity and content
      of PCs in bone marrow. The advent of comparative genomic hybridization (CGH) has
      opened a new possibility for characterizing chromosomal aberrations in myeloma
      cells. CGH is one of the powerful global assays for detecting changes in DNA copy
      number in a given genomic complement. This method involves competitive
      hybridization of differentially labeled test DNA (tumor) and reference DNA
      (normal) to normal human metaphase chromosome spreads. Based on the relative
      intensity of the two fluorescent colors, regions of a chromosome with gain or
      loss can be identified in a single hybridization. One of the advantages of CGH is
      that it can make use of archival materials when frozen tissues are not available,
      thus greatly expanding the number of cases that can be analyzed. Prospective and
      retrospective application of CGH to tumor specimens would permit clinical
      correlative studies of changes in DNA copy number with a much greater power than
      conventional cytogenetic analysis. The detailed procedures for CGH, including DNA
      labeling, hybridization, fluorescence microscopy, digital image analysis, and
      data interpretation, as well as the limitations of CGH are discussed in this
      chapter.

PMID- 15968097
TI  - Southern blotting of IgH rearrangements in B-cell disorders.
AB  - Southern blotting is a method whereby DNA fragments in the gel are denatured by
      soaking in an alkali solution, carried out of the gel, and transferred onto a
      membrane. After drying the membrane, the DNA is fixed irreversibly. The net
      result is a replica on the membrane of the DNA fragment pattern from the agarose
      gel. This technique is used to demonstrate B-cell clonality in blood and bone
      marrow down to the 1% level, though more reliably at the 5% level. The analysis
      is relatively nonselective and will detect novel rearrangements in relapse that
      were not seen at diagnosis. Modifications of the technique have been used to
      determine illegitimate switch recombinations and mutations of oncogenes.

PMID- 15968098
TI  - Identification and assembly of V genes as idiotype-specific DNA fusion vaccines
      in multiple myeloma.
AB  - Tumor-specific markers are important in identifying and tracking malignant cells.
      In this regard, functionally rearranged immunoglobulin variable (V) region genes
      in B-cell tumors fulfill and extend these criteria. V genes provide signature
      motifs in tumor cells and can delineate critical features of the clonal history
      of the cell of origin. They also define a tumor-specific antigen, which can be
      targeted for immunotherapy. Our focus has been on using novel DNA fusion vaccines
      to induce antitumor immunity. Here, we describe in detail the methods for
      identifying tumor-derived V genes at the nucleotide level in the malignant plasma
      cells of multiple myeloma. We further present the methodology for assembly of
      tumor V genes as single-chain variable region fragments (scFv), fused in frame
      with an immunopotentiating nontoxic bacterial sequence, Fragment C (FrC) of
      tetanus toxin. These scFv.FrC DNA vaccines provide protection in myeloma models
      and are currently in clinical trials. The vaccines are patient specific and can
      be rapidly assembled for clinical use.

PMID- 15968099
TI  - Identification of clonotypic IgH VDJ sequences in multiple myeloma.
AB  - In multiple myeloma (MM) the rearranged immunoglobulin heavy chain (IgH)
      variable, diversity, and joining (VDJ) DNA sequence of malignant plasma cells
      (PCs) serves as a marker for cells in the MM clone. This clonotypic sequence can
      be isolated from MM PCs by reverse transcriptase polymerase chain reaction (RT
      PCR) with consensus primers that amplify the rearranged IgH repertoire. This
      chapter focuses on the key steps in determining patient-specific clonotypic
      sequences, including bulk RT-PCR using purified bone marrow mononuclear cell
      (BMMC) RNA, single-cell RT-PCR using RNA from PCs sorted by flow cytometry, IgH
      sequence alignments using IMGT or V BASE, and patient-specific primer design. In
      a test panel of several MM patient BMMCs, primers specific for the proposed
      sequence must amplify IgH from only the original patient. Furthermore, the
      proposed IgH sequence is not confirmed as clonotypic until these primers generate
      positive amplifications in the majority of single PCs from the original patient.
      This two-part test ensures that the proposed IgH sequence satisfies the
      definition of the clonotypic sequence as the most frequent, unique IgH sequence
      in an MM patient PC sample. With this patient-specific MM marker, a better
      understanding of transformed PCs and their B-lineage predecessors can be
      developed.

PMID- 15968100
TI  - Real-time polymerase chain reaction of immunoglobulin rearrangements for
      quantitative evaluation of minimal residual disease in myeloma.
AB  - The evaluation of minimal residual disease (MRD) is critical in the evaluation of
      treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative
      evaluation of MRD now has a 10-yr-long history, but it remains a relatively
      sophisticated procedure. More recently, real-time quantitative approaches have
      also been developed. These approaches allow a very effective monitoring of
      disease but introduce additional complexity and costs to the procedure. This
      chapter describes how we currently perform real-time polymerase chain reaction
      (PCR) in MM. Compared to the first description of the assay in June 2000,
      significant improvements have been made. Although real-time PCR is the main focus
      of the chapter, most of the information suitable for a proper setup of a
      qualitative approach is also provided.

PMID- 15968101
TI  - Incomplete DJH rearrangements.
AB  - Analysis of Ig genes in B-cell malignancies has become an essential method in
      molecular diagnosis, and polymerase chain reaction (PCR) amplification of Ig
      heavy chain gene (IgH) rearrangements is now widely used for detection of
      clonality and minimal residual disease (MRD). Although several different
      sensitive protocols are now available for PCR analysis of IgH genes, they are
      frequently hampered owing to the high rate of somatic hypermutation present in
      multiple myeloma (MM). We recently described a new approach using incomplete DJH
      rearrangements as an alternative target. About 60% of MM samples contain an
      incomplete DJH rearrangement, 90% of them lacking on somatic mutations. This
      approach allows resolution of problems derived from primer mismatches, making DJH
      rearrangement a reliable and sensitive target for detection of clonality and MRD
      investigation in MM.

PMID- 15968102
TI  - Identification of malignant plasma cells by mRNA in situ hybridization.
AB  - Patients with multiple myeloma have a clonal proliferation of malignant plasma
      cells, each with an identical rearrangement of immunoglobulin heavy and light
      chain genes. When these unique sequences are determined, a valuable molecular
      tool is available that can been used to detect the presence of the malignant
      population. Previous methods have employed oligonucleotides derived from these
      sequences and allele-specific polymerase chain reaction to detect clonality. The
      method described in this chapter uses mRNA in situ hybridization (ISH) to
      demonstrate the presence of individual malignant cells. Single-cell analysis
      using mRNA ISH provides opportunities that when combined with immunophenotyping
      offer a valuable new investigative tool.

PMID- 15968103
TI  - The SCID-hu myeloma model.
AB  - The severe combined immune deficient human (SCID-hu) myeloma model is the only
      available model in which primary myeloma cells grow in vivo in a human bone
      marrow micro environment. A SCID mouse receives an implanted human fetal bone
      into which myeloma cells are directly injected. Through interaction with the
      human bone marrow microenvironment, the myeloma cells induce typical myeloma
      manifestations in the SCID host, such as the appearance of M protein in the
      serum, and changes in the implanted human bone, which often result in osteolysis
      of the human bone. The model provides the only platform for in vivo investigation
      of the biology and therapy of primary human myeloma in a human microenvironment.
      This chapter describes in detail all the steps necessary to establish this model
      and evaluate its success.

PMID- 15968104
TI  - The 5T2MM murine model of multiple myeloma: maintenance and analysis.
AB  - Multiple myeloma is a B-cell neoplasm characterized by the monoclonal
      proliferation of plasma cells in the bone marrow, the development of osteolytic
      lesions, and the induction of angiogenesis. These different processes require
      three-dimensional interactions, with both humoral and cellular contacts. The 5TMM
      models are suitable to study these interactions. These are murine models that
      originate from spontaneously developed myeloma in elderly mice. They are
      propagated by in vivo transfer of the myeloma cells into young syngeneic mice. We
      report methods involving the maintenance of the 5T2MM model and the
      quantification of tumor burden (by determining serum paraprotein concentration
      and plasmacytosis), assessment of bone lesions, and quantification of
      angiogenesis. The combination of these different techniques in these models not
      only helps in unraveling basic biological processes but also in the testing of
      potentially new therapeutic targets.

PMID- 15968105
TI  - Determination of telomerase activity and telomere length.
AB  - Telomerase is an enzyme that has been attracting much attention in recent years
      because its activities are so central to the processes of malignant
      transformation. It is a reverse transcriptase enzyme that can synthesize
      telomeric DNA using its own RNA component as a template. Without telomerase,
      telomeres will shorten until, at a critical length, cells enter senescence and
      die. The low level or absence of telomerase activity in most nonneoplastic
      tissues and somatic cells, and its presence in almost all malignant tumors is
      thus of great interest for potential diagnostic, prognostic, and therapeutic
      applications in the management of human cancer. It has been documented that high
      telomerase activity and short telomere length correlate with poor prognosis in
      patients with multiple myeloma, and antitelomerase therapy has become a novel
      therapeutic approach for the disease. Thus, determination of telomerase activity
      and telomere length is essential in the study of cancer. In this chapter, we
      provide a standard telomeric repeat amplification protocol for telomerase
      activity assay and a Southern blot terminal restriction fragment protocol for
      telomere length assay. We also discuss comparison with related assay methods.

PMID- 15968106
TI  - Dendritic cell/myeloma hybrid vaccine.
AB  - Dendritic cell (DC)-tumor fusion hybrid vaccine that facilitates antigen
      presentation represents a new, powerful strategy in cancer therapy. We
      investigated the antitumor immunity derived from vaccination of fusion hybrids
      between wild-type J558 or engineered J558-IL-4 myeloma cells secreting cytokine
      interleukin-4 (IL-4) and DCs. The design and methods for generation of mature
      bone marrow-derived DCs, preparation of DC/J558-IL-4 hybrid, and in vivo animal
      studies of DC/myeloma hybrid vaccine are described. Our data show that the fusion
      efficiency was approx 20% by using polyethylene glycol. Our data also show that
      immunization of C57BL/6 mice with engineered DC/J558-IL-4 hybrids elicited
      stronger J558 tumor-specific cytotoxic T-lymphocyte responses in vitro and
      induced more efficient protective immunity against J558 tumor challenge in vivo
      than DC/J558 hybrid vaccines.

PMID- 15968107
TI  - Genetically engineered myeloma cell vaccine.
AB  - Tumor cells engineered to express immunogenes have been used for cancer vaccines
      to induce antitumor immunity and to study the antitumor immune mechanisms derived
      from immunogene expression. In this chapter, we describe the design and methods
      for cloning a cDNA gene coding for the mouse CD40L molecule and for construction
      of the expression vector pcDNA-CD40L, as well as the methods for generation of
      engineered myeloma cells J558/CD40L expressing CD40 ligand. We also demonstrate
      that the engineered J558/CD40L tumor cells lose their tumorigenicity in syngeneic
      mice, and that the inoculation of J558/CD40L tumor cells further leads to
      protective immunity against wild-type J558 tumors.

PMID- 15968108
TI  - An in vitro osteoclast-forming assay to measure myeloma cell-derived osteoclast
      activating factors.
AB  - Much of the morbidity and mortality associated with the plasma cell (PC)
      malignancy, multiple myeloma (MM), is owing to the severe osteolytic bone disease
      seen in patients with this disease. Although the molecular mechanisms responsible
      for osteolysis remain to be fully elucidated, it is clear from numerous studies
      that it is owing, in part, to an increase in osteoclastic bone resorption.
      Several known osteoclast (OC)-activating factors (OAFs) are produced by myeloma
      PCs (MPCs), or by stromal cells in response to MPCs and include interleukin-1beta
      (IL-1beta); tumor necrosis factor-alpha (TNF-alpha); IL-6; parathyroid hormone
      related protein; macrophage inflammatory protein-1alpha; and, most recently, the
      TNF-ligand family member receptor activator of nuclear factor-kappaB ligand
      (RANKL). The identification and significance of any one of these myeloma-derived
      OAFs is dependent on robust and reliable assays that measure the de novo
      formation and activation of OCs. A number of in vitro assay systems have been
      described that examine the requirements for normal OC formation and are easily
      adaptable for examining which MM-derived OAF and to what extent it is responsible
      for the bone loss observed in individuals with myeloma. This chapter describes
      one such in vitro model system.

PMID- 15968109
TI  - Clonality detection of expanded T-cell populations in patients with multiple
      myeloma.
AB  - Expanded T-cell clones in the peripheral blood of patients with multiple myeloma
      and smoldering myeloma are usually CD8 positive and persist over long periods,
      suggesting that they are the result of chronic antigenic stimulation. The
      presence of enlarged T-cell clones can be demonstrated as bands other than the
      germ-line bands on Southern blots probed for the T-cell receptor beta gene
      (Vbeta), or defined by anti-TCRVbeta monoclonal antibody staining. However, the
      most sensitive way to demonstrate clonality within a population of T-cells is by
      analysis of the length of complementarity-determining region 3 of the rearranged
      TCR gene, followed by sequencing. Furthermore, my colleagues and I have
      previously shown that the CD57+ T-cells expressing the "expanded" TCRVbeta are
      monoclonal or biclonal, whereas the CD57- cells are usually polyclonal.

PMID- 15968110
TI  - Detecting mismatch repair defects in myeloma.
AB  - Defects in the mismatch repair system are associated with a microsatellite
      unstable phenotype. In this chapter, we describe the preparation of purified
      plasma cells using CD138 magnetic microbeads as a source of tumor DNA. We also
      describe a robust, sensitive method for comparing microsatellite repeat units of
      tumor to constitutive DNA using polymerase chain reaction and laser scanning of
      fluorescently labeled amplicons in an automated sequencer in order to assess
      microsatellite instability in myeloma.

PMID- 15968112
TI  - Making sense of DNA microarray data.

PMID- 15968111
TI  - Methylation-specific polymerase chain reaction.
AB  - Methylation-specific polymerase chain reaction (MSP) is a method that can rapidly
      assess the methylation status of virtually any group of CpG sites within a CpG
      island, independent of the use of methylation-sensitive restriction enzymes. This
      assay entails the initial modification of DNA by sodium bisulfite, converting all
      unmethylated cytosines to uracils but leaving the methylated cytosines unchanged,
      followed by subsequent amplification with primers specific for methylated vs
      unmethylated DNA. The great sensitivity of this technique allows qualitative
      methylation analysis from DNA obtained not only from fresh frozen tissues,
      peripheral blood, bone marrow, or body fluids but also from paraffin-embedded
      samples. It is a rapid and cost-effective method that does not require
      radioactive reagents and can be used for the analysis of a large number of
      clinical samples.

PMID- 15968114
TI  - Using softer X-ray absorption spectroscopy to probe biological systems.
AB  - Many inorganic species are now recognized as being essential for life, including
      many forms of sulfur, phosphate and numerous classes of metal ions. For example,
      recent progress in the fields of biochemistry and biology has pointed out the
      critical importance of sulfur in the biosynthesis of vital cofactors and active
      sites in proteins, and in the complex reaction mechanisms often involved. Special
      attention has also been drawn to the diverse roles of alkaline (Na(+), K(+)) and
      alkaline earth (Mg(2+), Ca(2+)) metal ions in mediating the activity of RNA,
      proteins and many processes in living cells. While the general effect of these
      ions in biology is mostly understood, information on their detailed role is
      deficient. Here the application of softer X-ray absorption spectroscopy (XAS) to
      probe the local structural and electronic environment of such ions within their
      biological complexes and during physiological reactions is discussed. In
      addition, the required experimental set-up and the difficulties associated with
      conducting softer XAS experiments on biological samples are presented.

PMID- 15968115
TI  - X-ray spectroscopy and X-ray diffraction at wavelengths near the K-absorption
      edge of phosphorus.
AB  - Phosphorus is an abundant element in living organisms. It is traceable by its X
      ray absorption spectrum which shows a strong white line at its K-edge, comparable
      with that observed for the L(III) edges of rare earth ions. With purple membrane,
      the variation of the imaginary part of the anomalous dispersion of phosphorus is
      found to be close to 20 anomalous electron units. Anomalous diffraction
      experiments at wavelengths near the K-absorption edge of phosphorus confirm this
      result. The spatial distribution of lipids derived from anomalous diffraction
      agrees with earlier results from neutron diffraction. Test experiments on single
      crystals of the carrier protein using 5.76 A photons gave a first low-resolution
      diffraction pattern. Various techniques of crystal mounting were attempted. In
      addition, fluorescence measurements on a solution of threonine synthase appear to
      hint at a change of the phosphate environment of the cofactor upon activator
      binding.

PMID- 15968116
TI  - Softer and soft X-rays in macromolecular crystallography.
AB  - The utilization and the potential of softer and soft X-rays in macromolecular
      crystallography as well as the challenges associated with the corresponding
      diffraction experiments and their possible remedies are reviewed.

PMID- 15968117
TI  - The use of softer X-rays in the structure elucidation of microporous materials.
AB  - Microporous materials, such as zeolites and aluminophosphates, have many
      applications as molecular sieves and shape-selective catalysts. This is due to
      their three-dimensional frameworks, which contain regular pores and channels, to
      their high acidity, arising from Bronsted and Lewis acid active sites, and to the
      incorporation of transition metal atoms into framework sites. This review firstly
      provides an introduction into the nature and properties of these materials, and
      their important applications; the difficulties in their full characterization and
      possible methods of elucidating their structures are then outlined; finally,
      methods of characterization, utilizing 'softer X-rays' are introduced. The first
      method is the determination of low concentrations of transition metals,
      incorporated into the frameworks using single crystal anomalous dispersion
      crystallography; synchrotron radiation is used to tune to the absorption edge of
      the metal atom in question, in order to change its signal relative to that of the
      rest of the structure, thereby allowing the pinpointing of its positions and the
      determination of its concentration at each site in the framework. Secondly, the
      use of longer wavelengths in powder diffraction studies is described, which, by
      stretching out the powder pattern, thereby reduces the overlapping of the
      diffraction peaks, thus allowing the structure to be solved by conventional
      direct methods. Finally, the use of X-ray absorption spectroscopy to determine
      the metal incorporation and the nature of coordination at the metal atom sites,
      in Mn silicalite-1 and FAPO-36, are described.

PMID- 15968118
TI  - Application notes on the use of softer X-rays for anomalous powder diffraction.
AB  - An in-vacuum diffractometer has been modified to collect powder diffraction data
      from a sample of promazine hydrochloride. Strong anomalous contrast has been
      observed at, or close to, the sulphur edge. Based on the data collected, a
      bespoke diffractometer has been designed that, together with minor changes to the
      geometry of the experiment, will enable the routine collection of powder data at
      absorption edges below 5.5 keV.

PMID- 15968119
TI  - Resonant soft X-ray diffraction - in extremis.
AB  - The use of softer-energy X-rays produced by synchrotron radiation for diffraction
      is an area of current interest. In this paper, experiments exploiting resonant
      scattering at the L absorption edges of 3d transition metal elements are
      reported. Such energies, typically 500-1000 eV, are at the extreme limit of soft
      X-ray diffraction where absorption effects are so severe that the sample and
      diffractometer must be placed in a windowless high-vacuum vessel. In addition,
      the Ewald sphere is so small as to likely contain, at most, only a single Bragg
      reflection. Advantages of using such radiation for the study of weak diffraction
      effects such as anomalous scattering, charge ordering, magnetic diffraction and
      orbital ordering are reported.

PMID- 15968120
TI  - Pure-type superconducting permanent-magnet undulator.
AB  - A novel synchrotron radiation source is proposed that utilizes bulk-type high
      temperature superconductors (HTSCs) as permanent magnets (PMs) by in situ
      magnetization. Arrays of HTSC blocks magnetized by external magnetic fields are
      placed below and above the electron path instead of conventional PMs, generating
      a periodic magnetic field with an offset. Two methods are presented to magnetize
      the HTSCs and eliminate the field offset, enabling the HTSC arrays to work as a
      synchrotron radiation source. An analytical formula to calculate the peak field
      achieved in a device based on this scheme is derived in a two-dimensional form
      for comparison with synchrotron radiation sources using conventional PMs.
      Experiments were performed to demonstrate the principle of the proposed scheme
      and the results have been found to be very promising.

PMID- 15968121
TI  - A new X-ray spectrometer with large focusing crystal analyzer.
AB  - A new focusing spectrometer employing Johann geometry has been built and
      permanently installed at the wiggler beamline W1 at the Hamburger Synchrotron
      Strahlungslabor (HASYLAB) am Deutschen Elektronen Synchrotron (DESY). It is now
      available for user operation. The design of the spectrometer is optimized for the
      use of a large source spot size at the DORIS storage ring as well as for simple
      operation and robustness under user-mode conditions. Nevertheless, the ideal
      source for enlarging the number of possible applications in the future would be
      an undulator at one of the PETRA III beamlines. In the following the spectrometer
      design is described and boundary conditions such as the available energy range
      for future experiments are discussed. Two benchmark experiments, resonant
      inelastic X-ray scattering (RIXS) and X-ray absorption fluorescence spectroscopy
      (XAFS), on samples with complicated matrices demonstrate the performance of the
      new instrument.

PMID- 15968122
TI  - A high-throughput structural biology/proteomics beamline at the SRS on a new
      multipole wiggler.
AB  - The North West Structural Genomics Centre's beamline, MAD10, at the SRS receives
      the central part of the radiation fan (0.5 mrad vertically, 4 mrad horizontally)
      produced by a new 2.46 T ten-pole wiggler. The optical arrangement of the
      beamline consists of a Rh-coated collimating Si mirror, a fixed-exit-beam double
      crystal monochromator with sagittal bending for horizontal focusing and a second
      Rh-coated Si mirror for vertical focusing. The double-crystal Si (111)
      monochromator allows data collection in the 5-13.5 keV photon energy range with
      rapid (subsecond) tunability and high energy resolution. The monochromatic beam
      is optimized through a 200 microm collimator. The beamline end station has been
      designed around a Mar desktop beamline with high-throughput cryogenic sample
      changer, Mar225 CCD detector, liquid-N(2) autofill system and an ORTEC C-TRAIN-04
      energy-resolving high-count-rate X-ray fluorescence detector. The instrument is
      optimized for MAD/SAD applications in protein crystallography with the additional
      mode of operation of online single-crystal EXAFS studies on the same crystals.
      Thus, screening of metals/Se in the crystal can be performed quickly prior to
      MAD/SAD data collection by exciting the crystal with X-rays of appropriate energy
      and recording an energy-dispersive fluorescence spectrum. In addition, this
      experimental set-up allows for parallel XAFS measurements on the same crystal to
      monitor 'radiation-induced' changes, if any, in e.g. the redox state of metal
      centres to be detected for a 'metallic' functional group during crystallographic
      data collection. Moreover, careful minimization of the thickness of the Be window
      maximizes the intensity performance for the 2.0-2.5 A softer wavelength range.
      This range also covers the K-edges of a number of important 3d transition metals
      as well as the L-edges of xenon and iodine and enhanced sulfur f ''.

PMID- 15968123
TI  - Improving the performance of high-resolution X-ray spectrometers with position
      sensitive pixel detectors.
AB  - A dispersion-compensation method to remove the cube-size effect from the
      resolution function of diced analyzer crystals using a position-sensitive two
      dimensional pixel detector is presented. For demonstration, a resolution of 23
      meV was achieved with a spectrometer based on a 1 m Rowland circle and a diced
      Si(555) analyzer crystal in a near-backscattering geometry, with a Bragg angle of
      88.5 degrees . In this geometry the spectrometer equipped with a traditional
      position-insensitive detector provides a resolution of 190 meV. The dispersion
      compensation method thus allows a substantial increase in the resolving power
      without any loss of signal intensity.

PMID- 15968124
TI  - Spherically bent analyzers for resonant inelastic X-ray scattering with intrinsic
      resolution below 200 meV.
AB  - Resonant inelastic X-ray scattering with very high energy resolution is a
      promising technique for investigating the electronic structure of strongly
      correlated materials. The demands for this technique are analyzers which deliver
      an energy resolution of the order of 200 meV full width at half-maximum or below,
      at energies corresponding to the K-edges of transition metals (Cu, Ni, Co etc.).
      To date, high resolution under these conditions has been achieved only with diced
      Ge analyzers working at the Cu K-edge. Here, by perfecting each aspect of the
      fabrication, it is shown that spherically bent Si analyzers can provide the
      required energy resolution. Such analyzers have been successfully produced and
      have greatly improved the energy resolution in standard spherically bent
      analyzers.

PMID- 15968125
TI  - X-ray microdiffraction and conventional diffraction from frozen-hydrated
      biological specimens.
AB  - A system for recording microdiffraction patterns from micrometer-sized quick
      frozen hydrated biological specimens at the high-flux beamline BL40XU of SPring-8
      is described. The optics consists of a pair of pinholes drilled into tantalum
      substratum, with a defining aperture of diameter 2 microm. The frozen specimens
      are placed in an in-vacuum cryochamber mounted on a three-axis goniometer, where
      the specimens are stably held at a liquid-nitrogen temperature ( approximately 74
      K). A beam size of 1.5 microm (full width at half-maximum) is attained at the
      sample position. By using this system, diffraction patterns have been recorded
      from an isolated single myofibril (diameter approximately 3 microm) of an insect
      flight muscle in an area equivalent to a single sarcomere (length approximately 3
      microm). The technique is potentially applicable to other micrometer-sized
      hydrated biological specimens, which are more susceptible to radiation damage
      than dry synthetic polymers or biopolymers. The quick-freezing of biological
      specimens has also been proven useful in reducing the specimen volume in the beam
      in conventional diffraction recordings.

PMID- 15968126
TI  - X-ray diffraction method for the investigation of contacts between solid
      surfaces.
AB  - A coherent X-ray scattering method for investigating the formation of the contact
      region between two solid surfaces is presented. Diffraction of X-rays from two
      crossed cylindrical quartz surfaces, coated with Cr and TiO(2), revealed a total
      contact area of 90 +/- 10 microm. In the so-called Hertz model for two surfaces
      in non-adhesive contact, this value is directly related to the displacement of
      the surfaces and the applied external force. Values of 40 +/- 3 nm for the
      displacement and 24 +/- 3 mN for the force are found. The method is also useful
      for studying liquids in confinement.

PMID- 15968127
TI  - On the refinement of time-resolved diffraction data: comparison of the random
      distribution and cluster-formation models and analysis of the light-induced
      increase in the atomic displacement parameters.
AB  - Expressions for the random-distribution and cluster-formation models for light
      induced changes in crystals studied by time-resolved diffraction are presented.
      The two models can be distinguished on the basis of differences in the predicted
      intensities. The light-induced increase in the atomic displacement parameters is
      analyzed with both simulated and experimental data sets.

PMID- 15968128
TI  - Lowest limit for detection of impurity concentration in semiconductors by
      fluorescence XAFS: resonant Raman scattering and angle dependence.
AB  - The lowest limit for detection (LLD) of the impurity concentration doped in
      semiconductors in the case of fluorescence XAFS measurements has been
      investigated as a function of the matrix of the impurity and the geometry of the
      measurement. When the impurity concentration is very low and other background
      noise is well suppressed, X-ray resonant Raman scattering by the constituent
      atoms of the matrix remains as a major background for the fluorescence-detected
      XAFS measurement. For example, in the fluorescence-detected XAFS measurement for
      Er-doped semiconductors at the Er L(III)-edge, the LLD of the Er concentration
      was about 5 x 10(14) to 1 x 10(15) cm(-2) for GaAs and GaP, and lower than 1 x
      10(14) cm(-2) for InP. The resonant Raman scattering of Ga atoms in the host
      semiconductor determines the LLD.

PMID- 15968129
TI  - A new cell for the study of in situ chemical reactions using X-ray absorption
      spectroscopy.
AB  - An in situ cell for reductive and oxidative treatments at different temperatures
      that allows the possibility of recording data as a function of temperature has
      been designed and constructed for X-ray absorption experiments at the GILDA
      beamline BM08 of ESRF. The cell is linked to a mass quadrupole spectrometer
      providing control of the reaction gases and monitoring of the products. The
      apparatus allows measurements to be performed both in transmission and
      fluorescence geometry. The cell was tested by studying the CO oxidation reaction
      promoted by a Pt/ceria-zirconia-supported catalyst. The CO(2) yield is correlated
      with the structural results confirming the existence of a strong metal-support
      interaction between the Pt metal clusters and the ceria-zirconia support.

PMID- 15968130
TI  - A method for normalization of X-ray absorption spectra.
AB  - Accurate normalization of X-ray absorption data is essential for quantitative
      analysis of near-edge features. A method, implemented as the program MBACK, to
      normalize X-ray absorption data to tabulated mass absorption coefficients is
      described. Comparison of conventional normalization methods with MBACK
      demonstrates that the new normalization method is not sensitive to the shape of
      the background function, thus allowing accurate comparison of data collected in
      transmission mode with data collected using fluorescence ion chambers or solid
      state fluorescence detectors. The new method is shown to have better reliability
      and consistency and smaller errors than conventional normalization methods. The
      sensitivity of the new normalization method is illustrated by analysis of data
      collected during an equilibrium titration.

PMID- 15968131
TI  - X-ray fluorescence methods for investigations of lipid/protein membrane models.
AB  - The protective effect of the bisphosphonate drug xydiphone (K,Na-ethidronate) on
      membrane-bound enzyme damaged by lead ions has been studied. A protein/lipid film
      of Ca-ATPase/phosphatedylethanolamine deposited on a silicon substrate was used
      as a model system. The position of lead ions within the molecular film before and
      after the xydiphone treatment was determined using the total-reflection X-ray
      fluorescence method. This technique is based on the simultaneous measurement of
      the X-ray reflection and the yield of the fluorescence radiation excited by X-ray
      inelastic scattering. The possibility of directly locating lead ions is the main
      advantage of this approach. Xydiphone has been found to effectively eliminate
      lead ions that have been incorporated into Ca-ATPase molecules during a
      preliminary incubation in lead acetate solution. The lead ions that were bound at
      the sites of the Ca-ATPase attachment to the phospholipid monolayer have proved
      to be inaccessible for xydiphone. A preliminary incubation of Ca-ATPase in the
      xydiphone solution precluded the incorporation of lead ions into the protein.

PMID- 15968132
TI  - VUV irradiation effects on proteins in high-flux synchrotron radiation circular
      dichroism spectroscopy.
AB  - Synchrotron radiation circular dichroism (SRCD) spectroscopy is emerging as an
      important new tool in structural molecular biology. Previously we had shown that
      in lower-flux SRCD instruments, such as UV1 at ISA and beamline 3.1 at the SRS,
      vacuum ultraviolet (VUV) radiation damage to proteins was not evident after
      exposure over a period of hours. No effects were detected in either the protein
      primary or the secondary structures. However, with the development of high-flux
      beamlines, such as CD12 at the SRS, this issue has been revisited because of
      changes observed in the SRCD spectra of consecutive scans of protein samples
      obtained on this high-flux beamline. Experiments have been designed to
      distinguish between two different possible mechanisms: (i) photoionization
      causing free radicals or secondary electrons producing degradation of the
      protein, and (ii) local heating of the sample resulting in protein denaturation.
      The latter appears to be the principal source of the signal deterioration.

PMID- 15968133
TI  - Overcoming protein denaturation caused by irradiation in a high-flux synchrotron
      radiation circular dichroism beamline.
AB  - It has been established that the new circular dichroism beamline CD12 has
      sufficiently high flux at low wavelengths to cause apparent irradiation problems
      with protein samples while their synchrotron radiation circular dichroism (SRCD)
      spectra are being collected. The cause of this effect has been extensively
      investigated and is reported in an accompanying paper [Wien et al. (2005). J.
      Synchrotron Rad. 12, 517-523.]. Experiments suggest that localized heating of the
      protein sample, leading to denaturation, is the probable cause. Methods to
      circumvent this problem by limiting the beam flux are reported. This was achieved
      using either an attenuation cell of water placed beam-side of the sample cell, or
      limiting the beam cross-sectional area hitting the sample. Such methods are shown
      to result in substantial reduction or apparent complete removal of this protein
      denaturation over the course of collecting three successive spectra. Elimination
      of this denaturation problem enables multiple SRCD scans for protein samples to
      be collected, which are vital both for good practice and for statistically valid
      results.

PMID- 15968134
TI  - Atomic imaging in EBCO superconductor films by an X-ray holography system using a
      toroidally bent graphite analyzer.
AB  - X-ray fluorescence holography (XFH) is a new technique enabling the determination
      of the three-dimensional local atomic structure around a certain element. This
      method has been applied to analyze the local structure around Cu in 300 nm thin
      films of EuBa(2)Cu(3)O(7-delta) (EBCO) epitaxially grown on MgO (100) substrate,
      using the newest system for XFH measurement and high-brilliance synchrotron
      radiation at SPring-8. Here, the results of a study on the irradiation effect on
      the local atomic structure of EBCO superconductor with XFH measurements are
      presented.

PMID- 15968135
TI  - High-energy phase-contrast X-ray imaging using a two-crystal X-ray
      interferometer.
AB  - To broaden the scope of phase-contrast X-ray imaging in biomedical applications,
      the energy of X-rays in a large-area imaging system using a two-crystal X-ray
      interferometer has been increased from 17.7 keV to 35 keV. The use of higher
      energy X-rays makes it possible to observe larger samples having greater
      variation in density within shorter measurement periods, at higher spatial
      resolution, and at lower X-ray doses. After optimizing the imaging system for 35
      keV X-rays, a 25 mm x 30 mm interference pattern with 50% visibility was
      generated at the Photon Factory. The system's capabilities are demonstrated by
      this pattern and a high-quality three-dimensional image of a rat heart.

PMID- 15968136
TI  - ATHENA, ARTEMIS, HEPHAESTUS: data analysis for X-ray absorption spectroscopy
      using IFEFFIT.
AB  - A software package for the analysis of X-ray absorption spectroscopy (XAS) data
      is presented. This package is based on the IFEFFIT library of numerical and XAS
      algorithms and is written in the Perl programming language using the Perl/Tk
      graphics toolkit. The programs described here are: (i) ATHENA, a program for XAS
      data processing, (ii) ARTEMIS, a program for EXAFS data analysis using
      theoretical standards from FEFF and (iii) HEPHAESTUS, a collection of beamline
      utilities based on tables of atomic absorption data. These programs enable high
      quality data analysis that is accessible to novices while still powerful enough
      to meet the demands of an expert practitioner. The programs run on all major
      computer platforms and are freely available under the terms of a free software
      license.

PMID- 15968139
TI  - Molecular cloning of monkey histamine H4 receptor.
AB  - Histamine H(4) receptor is considered as a novel therapeutic target for allergic
      diseases. To enhance the knowledge about species difference, which is essential
      for drug discovery research, monkey H(4) receptor was identified. Monkey H(4)
      receptor was characterized to have comparable similarity with its human
      counterpart. Discovery of monkey H(4) receptor will contribute to a better
      interpretation of effective drug discovery.

PMID- 15968140
TI  - A simple in vivo atrial fibrillation model of rat induced by transesophageal
      atrial burst pacing.
AB  - A simple in vivo closed-chest atrial fibrillation (Af) model of rats was
      developed. Af was reproducibly induced by transesophageal atrial burst pacing for
      30 s in each of the pentobarbital-anesthetized rats, whereas the
      cardiohemodynamic condition as well as the inducibility and duration of Af
      episode was stable over time. Moreover, the anti-Af effect of the class Ic drug
      pilsicainide was confirmed in this model, which was essentially the same as those
      reported previously in other Af animal models and clinical practice. Thus, this
      new model may become an alternative to current techniques.

PMID- 15968141
TI  - Hippocampus-dependent memory formation: do memory type-specific mechanisms exist?
AB  - Long-term memory (LTM) formation requires gene transcription and de novo protein
      synthesis. The transcription factor CREB is required for hippocampus-dependent
      LTM formation, and it is activated by several signaling pathways, including
      protein kinase A (PKA), the mitogen activated protein/extracellular signal
      regulated kinases (MAPK or ERKs), and Ca(2+)/calmodulin kinases (CaMKs). However,
      it is unknown whether all types of hippocampus-dependent LTM use the same
      signaling to activate transcription, and whether the transcriptional output is
      the same. Here we present molecular genetic and behavioral studies to demonstrate
      that two types of hippocampus-dependent LTM formation, spatial and contextual,
      require different signaling molecules. This can be illustrated by the CaMK
      kinases, CaMKKalpha, and CaMKKbeta, which have converse roles. CaMKKalpha is
      required for contextual and CaMKKbeta is required for spatial LTM formation. This
      leads to the surprising conclusion that there are distinct types of hippocampus
      dependent LTM, which differ in their underlying molecular mechanisms.

PMID- 15968143
TI  - Computer-aided detection of lung nodules on chest CT: issues to be solved before
      clinical use.

PMID- 15968144
TI  - Imaging of the ischemic penumbra in acute stroke.
AB  - One of the main reasons for the soaring interest in acute ischemic stroke among
      radiologists is the advent of new magnetic resonance techniques such as diffusion
      weighted imaging. This new modality has prompted us to seek a better
      understanding of the pathophysiologic mechanisms of cerebral ischemia/infarction.
      The ischemic penumbra is an important concept and tissue region because this is
      the target of various recanalization treatments during the acute phase of stroke.
      In this context, it is high time for a thorough review of the concept, especially
      from the imaging point of view.

PMID- 15968145
TI  - Assessment of tissue viability using diffusion- and perfusion-weighted MRI in
      hyperacute stroke.
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between the
      diffusion and perfusion parameters in hyperacute infarction, and we wanted to
      determine the viability threshold for the ischemic penumbra using diffusion- and
      perfusion-weighted imaging (DWI and PWI, respectively). MATERIALS AND METHODS:
      Both DWI and PWI were performed within six hours from the onset of symptoms for
      12 patients who had suffered from acute stroke. Three regions of interest (ROIs)
      were identified: ROI 1 was the initial lesion on DWI; ROI 2 was the DWI/PWI
      mismatch area (the penumbra) that progressed onward to the infarct; and ROI 3 was
      the mismatch area that recovered to normal on the follow-up scans. The ratios of
      apparent diffusion coefficient (ADC), the relative cerebral blood volume (rCBV),
      and the time to peak (TTP) were calculated as the lesions' ROIs divided by the
      contralateral mirror ROIs, and these values were then correlated with each other.
      The viability threshold was determined by using the receiver operating
      characteristic (ROC) curves. RESULTS: For all three ROIs, the ADC ratios had
      significant linear correlation with the TTP ratios (p < 0.001), but not with the
      rCBV ratios (p = 0.280). There was no significant difference for the ADC and rCBV
      ratios within the ROIs. The mean TTP ratio/TTP delay between the penumbras' two
      ROIs showed a significant statistical difference (p < 0.001). The cutoff value
      between ROI 2 and ROI 3, as the viability threshold, was a TTP ratio of 1.29
      (with a sensitivity and specificity of 86% and 73%, respectively) and a TTP delay
      of 7.8 sec (with a sensitivity and specificity of 84% and 72%, respectively).
      CONCLUSION: Determining the viability thresholds for the TTP ratio/delay on the
      PWI may be helpful for selecting those patients who would benefit from the
      various therapeutic interventions that can be used during the acute phase of
      ischemic stroke.

PMID- 15968146
TI  - MR imaging of orbital inflammatory pseudotumors with extraorbital extension.
AB  - OBJECTIVE: To demonstrate a variety of MR imaging findings of orbital
      inflammatory pseudotumors with extraorbital extension. MATERIALS AND METHODS: We
      retrospectively reviewed the MR features of five patients, who were diagnosed
      clinically and radiologically as having an orbital inflammatory pseudotumor with
      extraorbital extension. RESULTS: The types of orbital pseudotumors were a mass in
      the orbital apex (n = 3), diffuse form (n = 2), and myositis (n = 1). The
      extraorbital extension of the orbital pseudotumor passed through the superior
      orbital fissure in all cases, through the inferior orbital fissure in two cases,
      and through the optic canal in one case. The orbital lesions extended into the
      following areas: the cavernous sinus (n = 4), the middle cranial fossa (n = 4),
      Meckel's cave (n = 2), the petrous apex (n = 2), the clivus (n = 2), the
      pterygopalatine fossa and infratemporal fossa (n = 2), the foramen rotundum (n =
      1), the paranasal sinus (n = 1), and the infraorbital foramen (n = 1). On MR
      imaging, the lesions appeared as an isosignal intensity with gray matter on the
      T1-weighted images, as a low signal intensity on the T2-weighted images and
      showed a marked enhancement on the post-gadoliniumdiethylene triamine pentaacetic
      acid (post-Gd-DTPA) T1-sequences. The symptoms of all of the patients improved
      when they were given high doses of steroids. Three of the five patients
      experienced a recurrence. CONCLUSION: MR imaging is useful for demonstrating the
      presence of a variety of extraorbital extensions of orbital inflammatory
      pseudotumors.

PMID- 15968147
TI  - Lung nodule detection on chest CT: evaluation of a computer-aided detection (CAD)
      system.
AB  - OBJECTIVE: To evaluate the capacity of a computer-aided detection (CAD) system to
      detect lung nodules in clinical chest CT. MATERIALS AND METHODS: A total of 210
      consecutive clinical chest CT scans and their reports were reviewed by two chest
      radiologists and 70 were selected (33 without nodules and 37 with 1-6 nodules, 4
      15.4 mm in diameter). The CAD system (ImageChecker CT LN-1000) developed by R2
      Technology, Inc. (Sunnyvale, CA) was used. Its algorithm was designed to detect
      nodules with a diameter of 4-20 mm. The two chest radiologists working with the
      CAD system detected a total of 78 nodules. These 78 nodules form the database for
      this study. Four independent observers interpreted the studies with and without
      the CAD system. RESULTS: The detection rates of the four independent observers
      without CAD were 81% (63/78), 85% (66/78), 83% (65/78), and 83% (65/78),
      respectively. With CAD their rates were 87% (68/78), 85% (66/78), 86% (67/78),
      and 85% (66/78), respectively. The differences between these two sets of
      detection rates did not reach statistical significance. In addition, CAD detected
      eight nodules that were not mentioned in the original clinical radiology reports.
      The CAD system produced 1.56 false-positive nodules per CT study. The four test
      observers had 0, 0.1, 0.17, and 0.26 false-positive results per study without CAD
      and 0.07, 0.2, 0.23, and 0.39 with CAD, respectively. CONCLUSION: The CAD system
      can assist radiologists in detecting pulmonary nodules in chest CT, but with a
      potential increase in their false positive rates. Technological improvements to
      the system could increase the sensitivity and specificity for the detection of
      pulmonary nodules and reduce these false-positive results.

PMID- 15968148
TI  - Subtle pleural metastasis without large effusion in lung cancer patients:
      preoperative detection on CT.
AB  - OBJECTIVE: We wanted to describe the retrospective CT features of subtle pleural
      metastasis without large effusion that would suggest inoperable lung cancer.
      MATERIALS AND METHODS: We enrolled 14 patients who had open thoracotomy attempted
      for lung cancer, but they were proven to be inoperable due to pleural metastasis.
      Our study also included 20 control patients who were proven as having no pleural
      metastasis. We retrospectively evaluated the nodularity and thickening of the
      pleura and the associated pleural effusion on the preoperative chest CT scans. We
      reviewed the histologic cancer types, the size, shape and location of the lung
      cancer and the associated mediastinal lymphadenopathy. RESULTS: Subtle pleural
      nodularity or focal thickening was noted in seven patients (50%) having pleural
      metastasis and also in three patients (15%) of control group who were without
      pleural metastasis. More than one of the pleural changes such as subtle pleural
      nodularity, focal thickening or effusion was identified in eight (57%) patients
      having pleural metastasis and also in three patients (15%) of the control group,
      and these findings were significantly less frequent in the control group patients
      than for the patients with pleural metastasis (p = 0.02). The histologic types of
      primary lung cancer in patients with pleural metastasis revealed as
      adenocarcinoma in 10 patients (71%) and squamous cell carcinoma in four patients
      (29%). The location, size and shape of the primary lung cancer and the associated
      mediastinal lymphadenopathy showed no significant correlation with pleural
      metastasis. CONCLUSION: If any subtle pleural nodularity or thickening is found
      on preoperative chest CT scans of patients with lung cancer, the possibility of
      pleural metastasis should be considered.

PMID- 15968149
TI  - Sonographically guided core biopsy of the breast: comparison of 14-gauge
      automated gun and 11-gauge directional vacuum-assisted biopsy methods.
AB  - OBJECTIVE: To compare the outcomes of 14-gauge automated biopsy and 11-gauge
      vacuum-assisted biopsy for the sonographically guided core biopsies of breast
      lesions. MATERIALS AND METHODS: We retrospectively reviewed all sonographically
      guided core biopsies performed from January 2002 to February 2004. The
      sonographically guided core biopsies were performed with using a 14-gauge
      automated gun on 562 breast lesions or with using an 11-gauge vacuum-assisted
      device on 417 lesions. The histologic findings were compared with the surgical,
      imaging and follow-up findings. The histologic underestimation rate, the repeat
      biopsy rate and the false negative rates were compared between the two groups.
      RESULTS: A repeat biopsy was performed on 49 benign lesions because of the core
      biopsy results of the high-risk lesions (n = 24), the imaging-histologic
      discordance (n = 5), and the imaging findings showing disease progression (n =
      20). The total underestimation rates, according to the biopsy device, were 55%
      (12/22) for the 14-gauge automated gun biopsies and 36% (8/22) for the 11-gauge
      vacuum-assisted device (p = 0.226). The atypical ductal hyperplasia (ADH)
      underestimation (i.e., atypical ductal hyperplasia at core biopsy and carcinoma
      at surgery) was 58% (7/12) for the 14-gauge automated gun biopsies and 20% (1/5)
      for the 11-gauge vacuum-assisted biopsies. The ductal carcinoma in situ (DCIS)
      underestimation rate (i.e., ductal carcinoma in situ upon core biopsy and
      invasive carcinoma found at surgery) was 50% (5/10) for the 14-gauge automated
      gun biopsies and 41% (7/17) for the 11-gauge vacuum-assisted biopsies. The repeat
      biopsy rates were 6% (33/562) for the 14-gauge automated gun biopsies and 3.5%
      (16/417) for the 11-gauge vacuum-assisted biopsies. Only 5 (0.5%) of the 979 core
      biopsies were believed to have missed the malignant lesions. The false-negative
      rate was 3% (4 of 128 cancers) for the 14-gauge automated gun biopsies and 1% (1
      of 69 cancers) for the 11-gauge vacuum-assisted biopsies. CONCLUSION: The
      outcomes of the sonographically guided core biopsies performed with the 11-gauge
      vacuum-assisted device were better than those outcomes of the biopsies performed
      with the 14-gauge automated gun in terms of underestimation, rebiopsy and the
      false negative rate, although these differences were not statistically
      significant.

PMID- 15968150
TI  - The mid-term efficacy and safety of a permanent nitinol IVC filter(TrapEase).
AB  - OBJECTIVE: 1) To evaluate the mid-term efficacy and safety of a permanent nitinol
      inferior vena cava (IVC) filter; 2) to evaluate filter effectiveness, filter
      stability and caval occlusion. MATERIALS AND METHODS: A prospective evaluation of
      the TrapEase IVC filter was performed on 42 patients (eight men, 34 women)
      ranging in age from 22 to 78 years (mean age 66 years). All patients were ill
      with a high risk of pulmonary embolism (PE). Indications for filter placement
      were: 1) deep vein thrombosis with recurrent thromboembolism; 2) and/or free
      floating thrombus with contraindication to anticoagulation; and 3) complications
      in achieving adequate anticoagulation. Follow-up evaluations (mean: 15.4 months,
      range: 2 to 28 months) were performed at 6- and 12-month intervals after the
      procedure and included clinical histories, chart reviews, plain film, Doppler
      ultrasounds, and contrasted abdominal CT scans. RESULTS: In follow-up
      evaluations, the data analysis revealed no cases of symptomatic PE. There were no
      cases of filter migration, insertion site thrombosis, filter fracture, or vessel
      wall perforation. During the study, there was one case of filter thrombosis;
      early symptomatic thrombosis that was successfully treated in the hospital. Of
      the 42 subjects, eight died. These deaths were not related to the filter device
      or the implantation procedure, but to the underlying disease. CONCLUSION: This
      study demonstrates that the TrapEase permanent IVC filter is a safe and an
      effective device with low complication rates and is best used in patients with
      thromboembolic disease with a high risk of PE.

PMID- 15968151
TI  - The role of popliteal lymph nodes in differentiating rheumatoid arthritis from
      osteoarthritis by using CE 3D FSPGR MR imaging: relationship of the inflamed
      synovial volume.
AB  - OBJECTIVE: We wanted to assess the role of the popliteal lymph nodes for
      differentiating rheumatoid arthritis (RA) from osteoarthritis (OA), and we also
      wanted to investigate the relationship between the popliteal lymph nodes and the
      inflamed synovial volume (ISV) by using contrast enhanced (CE), fat suppressed,
      three dimensional-fast spoiled gradient echo (3D-FSPGR) MR imaging. MATERIALS AND
      METHODS: Contrast enhanced 3D-FSGPR MR imaging of 94 knees (21 with RA and 73
      with OA) was analyzed. A lymph node was defined as being 'observed' if it could
      be seen in at least two planes of the three orthogonal reformatted planes. The
      number of observed lymph nodes, the mean of the smallest dimension of each lymph
      node and the existence of central fatty change were recorded. The OA group was
      graded according to the ISV calculated by a segmentation method: grade I was < 20
      cm(3); grade II ranged from 20 cm(3) to 40 cm(3); and grade III was > 40 cm(3).
      Statistical analysis of the number and the mean size of the popliteal lymph nodes
      among the four groups (the RA group and the grade I-III OA groups) was performed.
      RESULTS: The prevalence of the observed popliteal lymph nodes was significantly
      different between all the OA groups or between the grade III OA group and the RA
      group (p < 0.0001, 0.0001, respectively). The popliteal lymph node was observed
      in 32 out of 73 OA cases, whereas it was visible in all of the 21 RA cases. The
      number (mean +/- standard deviation) of lymph nodes in the grade I OA group, the
      grade II OA group, the grade III OA group and the RA group was 1.2 +/- 0.4, 1.2
      +/- 0.4, 1.3 +/- 0.5, and 2.7 +/- 1.1, respectively. The mean size (mean +/-
      standard deviation) of the lymph nodes was 3.8 +/- 1.0 mm, 3.6 +/- 1.1 mm, 4.1 +/
      0.8 mm, and 5.4 +/- 1.3 mm, respectively. The incidence of central fatty changes
      was significantly lower in the RA group than in all the OA groups and the grade
      III OA group. When differentiating RA from OA, and when the differentiation was
      confined to the RA group and grade III OA group, respectively, the criteria of
      the number of lymph nodes, their size, their central fatty change and a
      combination of all these three criteria showed statistical significance (Az
      values for the former were 0.869, 0.847, 0.776, and 0.942; Az values for the
      latter were 0.855, 0.799, 0.712, and 0.916). The number and mean size of the
      lymph nodes correlated with the ISVs (r = 0.49, p < 0.001; 0.50, 0.001,
      respectively). CONCLUSION: The number, size and central fatty changes in the
      popliteal lymph nodes observed on the MR images might serve as simple and useful
      markers in differentiating RA disease from OA disease. These markers would be
      particular helpful in cases of severe synovial enhancement where the ISVs of both
      RA and OA overlap. The number and mean size of the lymph nodes also correlated
      well with the ISV.

PMID- 15968152
TI  - Treatment of a sequential giant fusiform aneurysm of the basilar trunk.
AB  - We report an exceptional case of a de novo giant fusiform aneurysm of the basilar
      trunk, which developed shortly after the therapeutic occlusion of the right
      internal carotid artery for a fusiform carotid aneurysm. It would appear to be
      appropriate to call this entity a sequential giant fusiform aneurysm. The patient
      was successfully treated with endovascular occlusion of the giant basilar trunk
      aneurysm following bypass surgery.

PMID- 15968153
TI  - Ergotamine-induced upper extremity ischemia: a case report.
AB  - Ergotamine-induced limb ischemia is an extremely rare case. We present a case of
      a 64-year-old man, who developed ischemia on the right upper extremity due to
      long-term use of Ergot for migraine headache. Angiography revealed diffused,
      smooth, and tapered narrowing of the brachial artery. The patient was
      successfully treated with intravenous nitroprusside.

PMID- 15968154
TI  - Wound healing in the cornea: a review of refractive surgery complications and new
      prospects for therapy.
AB  - PURPOSE: The corneal wound healing response is of particular relevance for
      refractive surgical procedures since it is a major determinant of efficacy and
      safety. The purpose of this review is to provide an overview of the healing
      response in refractive surgery procedures. METHODS: Literature review. RESULTS:
      LASIK and PRK are the most common refractive procedures; however, alternative
      techniques, including LASEK, PRK with mitomycin C, and Epi-LASIK, have been
      developed in an attempt to overcome common complications. Clinical outcomes and a
      number of common complications are directly related to the healing process and
      the unpredictable nature of the associated corneal cellular response. These
      complications include overcorrection, undercorrection, regression, corneal stroma
      opacification, and many other side effects that have their roots in the biologic
      response to surgery. The corneal epithelium, stroma, nerves, inflammatory cells,
      and lacrimal glands are the main tissues and organs involved in the wound healing
      response to corneal surgical procedures. Complex cellular interactions mediated
      by cytokines and growth factors occur among the cells of the cornea, resulting in
      a highly variable biologic response. Among the best characterized processes are
      keratocyte apoptosis, keratocyte necrosis, keratocyte proliferation, migration of
      inflammatory cells, and myofibroblast generation. These cellular interactions are
      involved in extracellular matrix reorganization, stromal remodeling, wound
      contraction, and several other responses to surgical injury. CONCLUSIONS: A
      better understanding of the complete cascade of events involved in the corneal
      wound healing process and anomalies that lead to complications is critical to
      improve the efficacy and safety of refractive surgical procedures. Recent
      advances in understanding the biologic and molecular processes that contribute to
      the healing response bring hope that safe and effective pharmacologic modulators
      of the corneal wound healing response may soon be developed.

PMID- 15968155
TI  - A risk score as part of an evidence-based approach to the selection of corneal
      replacement surgery.
AB  - PURPOSE: There is currently no standardized methodology that permits preoperative
      prediction of the surgical technique or drug regimen for corneal grafting most
      likely to succeed for an individual patient. A score factor related to the chance
      of successful penetrating keratoplasty (PK) may assist in standardization of
      graft outcome reporting and evidence-based management. METHODS: The Risk Score
      (RS) is based on factors shown to reduce the probability of 1-year survival of
      conventional PK in increments, using published Australian Corneal Graft Registry
      data. To asses its validity, Kaplan-Meier survival curves from 156 corneal
      replacement surgeries, stratified by preoperative RS, were used to derive the
      probability of survival at 1 year for donor PK, with or without systemic
      immunosuppression, and for synthetic PK with the AlphaCor artificial cornea. The
      probability of survival was then plotted against RS for each regimen, producing a
      family of curves. RESULTS: The mean RS for immunosuppressed cases was higher than
      for nonimmunosuppressed cases. The AlphaCor group had the highest scores.
      AlphaCor survival is little affected by the factors that affect the risk of graft
      survival, whereas the probability of donor graft survival, immunosuppressed or
      not, is inversely related to RS. CONCLUSIONS: This study was designed to test a
      method that allows objective comparison of outcomes of different methods of
      corneal replacement for different risk categories. Analysis of this small dataset
      supports the validity of the concept and suggests that the Risk Score is a useful
      descriptive statistic. With a sufficient sample size, statistically significant
      evidence of the optimum management method for an individual patient with a
      particular risk profile could be determined such that a prospective patient's
      preoperative RS could be used to assist management decisions. In particular, data
      allowing separation of different immunosuppression regimes would be useful.
      Functional outcomes such as visual acuity would be more significant clinically
      than the survival end point used in this study and the system also could be
      adapted to different follow-up periods.

PMID- 15968156
TI  - Effect of glycemic control on refractive changes in diabetic patients with
      hyperglycemia.
AB  - PURPOSE: To investigate the effect of intensive glycemic control on hyperglycemia
      induced changes in refraction, corneal topography, lenticular and corneal
      thickness in diabetic patients. METHODS: Eighteen diabetic patients with plasma
      glucose >300 mg/dl were enrolled in the study consecutively. Autorefraction, C
      Scan corneal topography, Javal keratometry, corneal pachymetry and ultrasonic
      biometric measurements were carried out at presentation and after metabolic
      control of blood sugar (plasma glucose profile <200 mg/dl). One eye of each
      patient was selected randomly for statistical analysis. RESULTS: Mean plasma
      glucose levels were 356.00 mg/dl before and 133.78 mg/dl after treatment. The
      median values of the autorefractometric measurements were - 0.125 D on admission
      and + 0.375 D at the second examination. The difference in the refraction was
      statistically significant (P = 0.022). Nine of 18 patients became hyperopic, 2
      became myopic and 7 showed no change after treatment. There was a significant
      change in the corneal topographic keratometric measurements at the flattest
      corneal meridian after treatment (P = 0.037). After treatment no statistically
      significant changes were observed in the pachymetric corneal thickness, anterior
      chamber depth, biometric dioptric lens calculations and Javal keratometric data.
      CONCLUSIONS: Hyperglycemia is the major cause of the transient refractive changes
      in diabetic patients. Following intensive medical treatment, a considerable
      number of patients tend to become more hyperopic compared with the hyperglycemic
      state. During the treatment period, changes in the corneal topographic parameters
      might be a potential source of error for keratorefractive and cataract surgery.

PMID- 15968157
TI  - Validity of endothelial cell analysis methods and recommendations for calibration
      in Topcon SP-2000P specular microscopy.
AB  - PURPOSE: To report on the calibration of the Topcon SP-2000P specular microscope
      and the Endothelial Cell Analysis Module of the IMAGEnet 2000 software, and to
      establish the validity of the different endothelial cell density (ECD) assessment
      methods available in these instruments. METHODS: Using an external microgrid, we
      calibrated the magnification of the SP-2000P and the IMAGEnet software. In both
      eyes of 36 volunteers, we validated 4 ECD assessment methods by comparing these
      methods to the gold standard manual ECD, manual counting of cells on a video
      print. These methods were: the estimated ECD, estimation of ECD with a reference
      grid on the camera screen; the SP-2000P ECD, pointing out whole contiguous cells
      on the camera screen; the uncorrected IMAGEnet ECD, using automatically drawn
      cell borders, and the corrected IMAGEnet ECD, with manual correction of
      incorrectly drawn cell borders in the automated analysis. Validity of each method
      was evaluated by calculating both the mean difference with the manual ECD and the
      limits of agreement as described by Bland and Altman. RESULTS: Preset factory
      values of magnification were incorrect, resulting in errors in ECD of up to 9%.
      All assessments except 1 of the estimated ECDs differed significantly from manual
      ECDs, with most differences being similar (< or =6.5%), except for uncorrected
      IMAGEnet ECD (30.2%). Corrected IMAGEnet ECD showed the narrowest limits of
      agreement (-4.9 to +19.3%). CONCLUSIONS: We advise checking the calibration of
      magnification in any specular microscope or endothelial analysis software as it
      may be erroneous. Corrected IMAGEnet ECD is the most valid of the investigated
      methods in the Topcon SP-2000P/IMAGEnet 2000 combination.

PMID- 15968158
TI  - Limits of agreement between the optical pachymeter and a noncontact specular
      microscope.
AB  - PURPOSE: To determine the limits of agreement between central corneal thickness
      (CCT) measurements made with the slit lamp-attached optical pachymeter and the
      SP2000P noncontact specular microscope. METHODS: Triplicate readings for CCT were
      obtained for each of 130 (right) eyes of 130 patients, using the slit lamp
      attached optical pachymeter and then the SP2000P noncontact specular microscope.
      The average CCT measured by each method was compared. Subsequently, the mean
      difference between both sets of measurements was assessed, and the 95% confidence
      interval (limits of agreement) between both techniques was determined. RESULTS:
      The mean +/- SD CCT measured by the optical pachymeter was 543 +/- 34 microm and
      532 +/- 34 microm for the specular microscope. We found a statistically
      significant (P < 0.001) mean bias of 10 mum between CCT values measured with both
      types of equipment, with the optical pachymeter returning the higher values. The
      coefficient of variation was 6.3% for the optical pachymeter and 6.4% for the
      specular microscope. CONCLUSIONS: The right eye CCT measurements made by the
      optical pachymeter are, on average, 10 mum thicker than those made with the
      SP2000P specular microscope, which suggests that both pieces of equipment cannot
      be used interchangeably to monitor CCT changes in patients. Excluding left eye
      measurements, the reliability of the optical pachymeter is identical to that of
      the noncontact specular microscope.

PMID- 15968159
TI  - In vivo confocal microscopy of posterior polymorphous dystrophy.
AB  - PURPOSE: This study was designed to delineate the morphologic features of
      posterior polymorphous dystrophy (PPD) using in vivo confocal microscopy.
      METHODS: Six patients with clinically diagnosed PPD were examined by slit-lamp
      biomicroscopy, Orbscan II slit-scanning elevation topography, and in vivo
      confocal microscopy. RESULTS: Endothelial cell densities ranged from 613 to 3,405
      cells/mm and endothelial polymegathism was noted in all cases, whereas
      endothelial pleomorphism was not a prominent feature. Three cases exhibited
      bright endothelial nuclei. A variety of abnormal curvilinear and vesicular
      abnormalities were imaged by in vivo confocal microscopy, with lesions ranging
      between 6 and 159 microm in diameter. Abnormal endothelial cells were visible
      within some of these lesions. Six cases showed hyperreflectivity at the level of
      Descemet's membrane around the lesions. Deep stromal keratocytes appeared to
      aggregate around, or were compressed by, the endothelial lesions in one case.
      CONCLUSIONS: We report the largest case series of PPD imaged by in vivo confocal
      microscopy. The ability of in vivo confocal microscopy to assess the living
      cornea over time enables monitoring of disease progression and thus the potential
      to identify and correlate development of, or changes in, microstructural
      features. As more data become available, these analyses may enable the
      formulation of prognostic and diagnostic criteria.

PMID- 15968160
TI  - Management of pellucid marginal corneal degeneration.
AB  - PURPOSE: This study was designed to determine how patients with pellucid marginal
      corneal degeneration (PMCD) are managed in a tertiary corneal practice. METHODS:
      A retrospective chart review of 45 patients with PMCD from a corneal referral
      practice was performed. Information collected from the medical records included
      demographic data, best-corrected visual acuity, videokeratography, contact lens
      use, and surgical procedures. RESULTS: Forty-five patients (85 eyes; 30 males, 15
      females) with PMCD were included in this study. They were followed-up for an
      average of 4.7 years (standard deviation (SD), +/-8.7). Seventy-five eyes (88.2%)
      were managed nonsurgically with spectacles in 31 eyes (36.4%) or contact lenses
      in 44 eyes (51.8%). Contact lens management was initially attempted in 51 eyes
      (60%); however, 7 eyes failed contact lenses. Visual acuity of 0.5 (20/40) or
      better was noted in 34 eyes (75.5%) after contact lens fit. Ten eyes (11.8%)
      underwent penetrating keratoplasty with an average postoperative follow-up of 9
      years (SD, +/-8.2; 1.5-20.5). Clear grafts were present in all 10 eyes at the end
      of the study (average, 9 years; SD, +/-82). CONCLUSIONS: Nonsurgical management
      of PMCD continues to play a predominant role in the management of this disorder.
      Poor best-corrected visual acuity at presentation of 0.2 (20/100) or worse and
      long follow-up (8 years or more) were significantly associated with surgery.

PMID- 15968161
TI  - Tear function changes during interferon and ribavirin treatment in patients with
      chronic hepatitis C.
AB  - PURPOSE: To evaluate symptoms and changes in tear function and the ocular surface
      with interferon and ribavirin therapy for chronic hepatitis C. METHODS: Nineteen
      patients with chronic hepatitis C undergoing a course of interferon alfa
      2b/ribavirin therapy and 19 age- and sex-matched controls participated in this
      prospective study. Patients were evaluated for dry eye subjectively (15-symptom
      assessment questionnaire) and objectively, including ophthalmologic examination,
      Schirmer test, tear clearance rate (TCR), tear function index (TFI), and
      nucleus/cytoplasm (N/C) ratio of conjunctival epithelial cell by impression
      cytology. All tests were performed before antiviral therapy (baseline); at 1, 3,
      and 6 months after initiation of therapy; and at 3 and 6 months after completing
      the 6-month course of treatment. All the tear functional tests and impression
      cytology results in controls were compared with pretreatment baseline of study
      group, using the Student t test. A paired t test was used to compare mean patient
      follow-up values with mean patient baseline values. RESULTS: Patients' mean score
      on the dry eye symptom assessment questionnaire was significantly (P < 0.05)
      higher than baseline after 1 and 3 months of therapy, peaked after 6 months of
      therapy, remained significantly elevated at 3 months after completion of therapy,
      but had decreased to almost baseline by 6 months after cessation of therapy.
      Compared with baseline, mean Schirmer test values showed a significant change
      only at 1 month after the start of treatment. In contrast, mean TCR, mean TFI,
      and mean N/C ratio were significantly different from baseline at every
      examination, including 6 months after discontinuation of therapy. After 6 months
      of therapy, 4 patients (21%) had advanced squamous metaplasia (stage 3 or 4), but
      2 patients still had mild squamous metaplasia (stage 2) even 6 months after the
      completion of therapy. CONCLUSIONS: Impairment of tear dynamics and squamous
      metaplastic changes in the ocular surface occurred in patients with chronic
      hepatitis C treated with interferon alfa-2b and ribavirin. Symptoms of dry eye
      were mild and reversible; however, abnormalities in tear dynamics and the ocular
      surface persisted even 6 months after discontinuation of treatment.

PMID- 15968162
TI  - The effect of antireflection film use on blink rate and asthenopic symptoms
      during visual display terminal work.
AB  - PURPOSE: To investigate the effect of visual display terminal antireflection (AR)
      films on blink rate and subjective symptoms of asthenopia. METHODS: This was a
      nonrandomized, prospective clinical trial in which 7 healthy volunteers underwent
      blink rate measurements with a blink rate recording system while viewing a DVD on
      a computer display for 10 minutes. The measurements were carried out without an
      AR film on terminal displays initially. The same tasks were performed on the next
      day with an AR film on the displays. The subjects were also required to score
      their symptoms of asthenopia on a visual analog scale before and just after DVD
      viewing. The changes in blink rate and asthenopia scores with AR film use were
      assessed by the Student t test. RESULTS: The mean baseline blink rate was 15.7 +/
      5.9 blinks /min, which decreased significantly to 9.6 +/- 4.3 blinks/min after
      DVD viewing without an AR film (P < 0.05). The mean baseline and final blink
      rates for DVD viewing with an AR film were 14.6 +/- 9.2 and 14.3 +/- 9.2
      blinks/min, respectively. There were no significant differences between baseline
      and final blink rates after DVD viewing with an AR film (P > 0.05). The mean
      cumulative visual analog asthenopic symptom score after DVD viewing without an AR
      film was 72 +/- 18% compared with the mean cumulative symptom score of 52 +/- 11%
      after DVD viewing with an AR film. The difference was statistically significant
      (P < 0.05). CONCLUSIONS: Visual display terminal work appears to be associated
      with asthenopic symptoms and decreased blink rates. The use of AR films on
      computer displays may prevent both reflections of light from screen surfaces and
      reduction in blink rates resulting in fewer asthenopic symptoms.

PMID- 15968163
TI  - Evaluation of corneal endothelial pump function with a cold stress test.
AB  - PURPOSE: This study was designed to evaluate corneal endothelial pump function
      with a cold-stress test. METHODS: The study group was comprised of 16 healthy
      volunteers (20 eyes), 12 patients with penetrating keratoplasty (15 eyes), 9
      patients with decreased corneal sensitivity (9 eyes), and 7 patients with corneal
      endothelial anomaly (10 eyes). After measuring central corneal sensitivity,
      endothelial cell density, temperature, and thickness, cold stress was applied for
      10 minutes and corneal temperature and thickness were measured again. RESULTS:
      After cooling, the average corneal temperature decreased from 34.7 degrees C to
      26.0 degrees C. The degree of corneal swelling (percent increase in thickness)
      for the control, penetrating keratoplasty, decreased corneal sensitivity, and
      corneal endothelial anomaly groups was 1.25 +/- 0.89, 3.37 +/- 2.44, 4.72 +/-
      2.51, and 3.40 +/- 1.92 (% +/- standard deviation), respectively. There was a
      negative correlation between the degree of corneal swelling and corneal
      sensitivity, but not endothelial cell density, temperature, or thickness.
      CONCLUSION: Corneal sensitivity is an effective factor in assessing endothelial
      pump function.

PMID- 15968164
TI  - The New Zealand National Eye Bank study 1991-2003: a review of the source and
      management of corneal tissue.
AB  - PURPOSE: To evaluate donor demographics and source, donor tissue processing and
      storage, biologic contamination, and the utilization and distribution of corneal
      tissue procured by the New Zealand National Eye Bank. METHODS: As part of a
      prospective longitudinal study, the electronic records of the NZNEB for the 13
      year period 1991-2003 were analyzed for each year with respect to donor
      demographics, donor source and cause of death, death-to-preservation interval,
      storage methods, endothelial assessment, biologic contamination, corneal tissue
      utilization, and distribution. RESULTS: During the study period, 3221 corneas
      were retrieved from 1628 donors (69.8% male, 30.2% female), with the mean age of
      donors 59.4 years (SD 18.3 years) and range 4 to 95 years. No significant
      correlation was identified between donor age group (using 10-year intervals) and
      the proportion of corneas suitable for transplantation. Donors were procured from
      the Coroner's service (67.6%), public hospitals, (23.5%) and multiorgan donors
      (7.1%). The most common causes of donor death were cardiovascular disease,
      trauma, and cerebrovascular disease. Average storage duration increased from 3.5
      to 11.8 days when organ culture replaced hypothermic storage in 1992. Biologic
      contamination occurred in 5% of all donor corneas. The most common bacterial and
      fungal isolates were coagulase-negative staphylococci and Candida spp,
      respectively. A significant decrease in contamination rate over the years of the
      study was identified. Overall, 79.4% of corneal tissue procured was used for
      corneal transplantation (75.8% for penetrating keratoplasty, 2.1% for lamellar
      keratoplasty, and 1.5% for unspecified transplants), and 21.6% was discarded.
      Most common reasons for discarding tissue were biologic contamination, abnormal
      serology, and failed endothelial assessment. CONCLUSION: Analysis of the NZNEB
      database provides valuable information in relation to eye banking and corneal
      transplantation in New Zealand. Significant trends were identified in donor
      demographics, donor procurement source, improved donor tissue processing and
      storage, decreased biologic contamination, and increased utilization of corneal
      tissue.

PMID- 15968165
TI  - p53 Expression in pterygium by immunohistochemical analysis: a series report of
      127 cases and review of the literature.
AB  - PURPOSE: To assess the p53 protein expression in pterygial tissue and to review
      all immunohistochemical studies on pterygium from Medline to evaluate the roles
      of age, gender, race, p53 antibody, cutoff levels of immunohistochemical
      analysis, parts of pterygium, p53 gene mutation spectrum, and primary or
      recurrent pterygium on the p53 staining results. METHODS: Immunohistochemical
      staining was performed on 127 pterygial specimens and 18 normal conjunctival
      samples. All 8 immunohistochemical studies on p53 expression in pterygium from
      Medline were reviewed. RESULTS: Among the 127 pterygial samples, there were 29
      specimens (22.8%) positive for p53 expression. There was no significant
      difference between the p53-positive and p53-negative groups with respect to age
      or gender. CONCLUSION: The positive rate of p53 staining in 8 immunohistochemical
      studies was 7.9%, 36.8%, 37.5%, 38.1%, 50%, 53.8%, 60%, and 100%, respectively.
      p53 protein antibody, cutoff level, race, and p53 gene mutational spectra all
      affect the results on the p53 staining. Different parts of pterygium and gender
      merit further evaluation in their role on p53 staining result.

PMID- 15968166
TI  - Deep lamellar endothelial keratoplasty: surgery in complex cases with severe
      preoperative visual loss.
AB  - PURPOSE: This study was designed to report the use of deep lamellar endothelial
      keratoplasty (DLEK) in combination with other intraocular surgeries in the
      treatment of eyes with severe bullous keratopathy and visual loss. METHODS: DLEK
      surgery was performed in six patients with severe bullous keratopathy and
      preoperative vision with a range of between count fingers and light perception
      only. DLEK was combined with vitrectomy and placement of a ciliary sulcus sutured
      intraocular lens in four patients and with cataract surgery in one patient. Two
      patients with vitreoretinal disease underwent pars plana vitrectomy within only 4
      months after the DLEK donor tissue had been placed. Graft clarity, Snellen visual
      acuities, refractive astigmatism, endothelial cell counts, and corneal topography
      were prospectively measured at 6 and 12 months postoperatively. RESULTS: At 6
      months after DLEK surgery, all grafts were clear and vision improved in all
      patients. Best spectacle-corrected visual acuity improved from count fingers
      level (or worse) before surgery to a range of 20/40 to 20/200 after surgery.
      Average refractive astigmatism at 6 months was 2.0 diopters (range, 0.50-4.00
      diopters). The average postoperative endothelial cell count was 1,679 +/- 380
      (range, 1,200-2,298) cells/mm at 6 months and 1,449 +/- 365 (range, 1,105-2,043)
      cells/mm at 12 months. Vitreoretinal surgery subsequent to graft placement did
      not affect corneal clarity or dislodge the grafted tissue. CONCLUSIONS: DLEK
      surgery can be used in cases with severe visual loss caused by bullous
      keratopathy with transfer of healthy donor endothelium, clearing of the central
      cornea, and restoration of useful vision. DLEK also can be successfully combined
      with other intraocular surgeries such as vitrectomy, intraocular lens exchange,
      and sutured intraocular lens surgery. The DLEK graft can tolerate subsequent
      intraocular surgery performed as early as 3 months after placement of the donor
      tissue.

PMID- 15968167
TI  - Fibrin sealant in corneal stem cell transplantation.
AB  - PURPOSE: To determine if transplanted corneal epithelial stem cells are safely
      and efficiently attached to the deficient limbal niche with use of fibrin
      sealant. The primary outcome is measured with respect to the stability of the
      transplant, with secondary qualitative evaluations of inflammation, patient
      comfort, speed of operation, and incidence of complications. METHODS: This
      retrospective case study examined a total of 114 corneal stem cell
      reconstructions performed in 95 patients from 1996 to 2004 using corneal stem
      cells primarily, with a minority of amnion alone, or both. Fibrin sealant was
      used as the only technique of stem cell adhesion for limbal reconstruction for
      primary or recurrent pterygia and various stem cell-deficient diseases from 2000
      to 2004. RESULTS: The fibrin sealant group showed 1 small recurrence of pterygium
      but no complications. With sutures, there were 3 recurrences in the pterygia
      group. After completion of all surgical procedures, all patients were free of
      pterygia. Miscellaneous stem cell deficiencies were included to demonstrate that
      corneal stem cell transplants can be used in other corneal procedures in addition
      to pterygia. CONCLUSIONS: Fibrin sealant alone effectively and safely attached
      corneal stem cell transplants to the limbal niche. The additional qualitative
      observations of a reduction in operation time, postoperative pain, and
      inflammation augurs for more extensive use of fibrin sealants in ophthalmology.

PMID- 15968168
TI  - Confocal microscopy of posterior polymorphous endothelial dystrophy.
AB  - PURPOSE: To report the in vivo confocal microscopic findings of posterior
      polymorphous endothelial dystrophy (PPED). METHODS: Four patients with PPED from
      2 unrelated families and 2 asymptomatic children of an index patient were
      included in this observational case series. The eyes of the 6 subjects were
      examined by confocal light microscopy. RESULTS: Confocal microscopy demonstrated
      craters, streaks, and cracks over the corneal endothelium surface. Pleomorphism
      and polymegathism were present in eyes with PPED. Guttae and clusters of abnormal
      endothelial cells were also identified in corneas of these PPED patients. These
      findings were absent in eyes without clinical manifestations of PPED.
      CONCLUSIONS: In vivo confocal microscopy is potentially useful for excluding
      suspected cases of subclinical PPED. Abnormalities in the Descemet membrane and
      endothelium were observed.

PMID- 15968169
TI  - Bacterial contamination of human organ-cultured corneas.
AB  - PURPOSE: This study was designed to define the risk of contamination of human
      corneas preserved by the organ-culture method. METHODS: We examined the microbial
      contaminations in 3,100 corneoscleral rims cultivated in our eye bank.
      Microbiologic tests were performed in the preservation medium 5 days after the
      beginning of cornea cultures and in the last day of culture (21.5 +/- 8.1 days),
      when the corneas were transferred to the deswelling medium. In 1,029 corneas a
      microbiologic test also was performed 1 day after the beginning of deswelling
      procedure. RESULTS: We found 206 microbial contaminations (6.65% of total) after
      5 days and 17 (0.55%) at the end of the preservation period. The total number of
      contaminated samples during the cornea culture was 223 corresponding to 7.2% of
      the samples (95% confidence interval, 6.3-8.1). The 1,029 tests performed during
      the deswelling step disclosed 26 contaminated cornea cultures despite apparent
      sterility of the medium (2.5%; 95% confidence interval, 1.5-3.5). CONCLUSIONS:
      The observation of microbial contaminations in a time close to the transplant
      (i.e., at the end of the preservation period and in the deswelling step) showed
      that a fast microbial tests during the deswelling procedure may prevent the
      grafting of a contaminated cornea. The appearance of bacteria in the deswelling
      medium despite a negative culture medium suggests that bacteria penetrate the
      corneal tissues during the culture to be subsequently extruded when the internal
      fluids move outward.

PMID- 15968170
TI  - Epithelial innervation of human cornea: a three-dimensional study using confocal
      laser scanning fluorescence microscopy.
AB  - PURPOSE: Evaluation of a new method to visualize distribution and morphology of
      human corneal nerves (Adelta- and C-fibers) by means of fluorescence staining,
      confocal laser scanning microscopy, and 3-dimensional (3D) reconstruction.
      METHODS: Trephinates of corneas with a diagnosis of Fuchs corneal dystrophy were
      sliced into layers of 200 microm thickness using a Draeger microkeratome (Storz,
      Germany). The anterior lamella was stained with the Life/Dead-Kit (Molecular
      Probes Inc.), examined by the confocal laser scanning microscope "Odyssey XL,"
      step size between 0.5 and 1 microm, and optical sections were digitally 3D
      reconstructed. RESULTS: Immediate staining of explanted corneas by the Life/Dead
      Kit gave a complete picture of the nerves in the central human cornea. Thin
      nerves running parallel to the Bowman layer in the subepithelial plexus perforate
      the Bowman layer orthogonally through tube-like structures. Passing the Bowman
      layer, Adelta- and C-fibers can be clearly distinguished by fiber diameter, and,
      while running in the basal epithelial plexus, by their spatial arrangement.
      Adelta-fibers run straight and parallel to the Bowman layer underneath the basal
      cell layer. C-fibers, after a short run parallel to the Bowman layer, send off
      multiple branches penetrating epithelial cell layers orthogonally, ending blindly
      in invaginations of the superficial cells. In contrast to C-fibers, Adelta-fibers
      show characteristic bulbous formations when kinking into the basal epithelial
      plexus. CONCLUSIONS: Ex-vivo fluorescence staining of the cornea and 3D
      reconstructions of confocal scans provide a fast and easily reproducible tool to
      visualize nerves of the anterior living cornea at high resolution. This may help
      to clarify gross variations of nerve fiber patterns under various clinical and
      experimental conditions.

PMID- 15968171
TI  - Particle-mediated gene transfer of opioid growth factor receptor cDNA regulates
      cell proliferation of the corneal epithelium.
AB  - PURPOSE: This study was designed to determine at the molecular level whether
      interactions between the opioid growth factor (OGF) and OGF receptor (OGFr) play
      a role in regulating DNA synthesis in the homeostasis of the corneal epithelium.
      METHODS: The plasmid pcDNA3.1+OGFr-HA, carrying the rat OGFr cDNA epitope-tagged
      with a C-terminal hemagglutinin (HA), or the empty-vector (pcDNA3.1+), was
      delivered twice by the Helios Gene Gun System at 300 psi to the cornea of
      anesthetized rats. The contralateral (untreated) cornea served as the naive
      specimen. BrdU was used to determine whether the recombinant OGFr was effective
      in regulating DNA synthesis in the rat peripheral corneal epithelium. RESULTS:
      Within 18 hours of transfection, positive HA staining was apparent in both the
      basal and suprabasal layers (efficiency > 90% of the cells) throughout the
      central and peripheral cornea. Quantitative immunohistochemistry with rhodamine
      conjugated anti-OGFr antibodies revealed twofold more OGFr expression in the
      central and peripheral epithelium of transfected corneas relative to naive
      corneas. The number of BrdU-positive basal cells in the peripheral epithelium of
      the transfected cornea was one-third of that in the naive cornea. CONCLUSIONS:
      These data demonstrate the direct role of the OGF-OGFr system in determining
      cellular renewal in the mammalian corneal epithelium. Moreover, the successful
      establishment of a novel delivery system of cDNAs to the ocular surface suggests
      a therapeutic role for gene therapy in the eye.

PMID- 15968172
TI  - Filamentary keratopathy as a chronic problem in the long-term care of patients in
      a vegetative state.
AB  - PURPOSE: To emphasize that filamentary keratopathy may occur in the long-term
      care of patients in a vegetative state. METHODS: Clinical observation of 2 young
      patients who had survived 16 and 8(1/2) years, respectively, in a vegetative
      state after an acute traumatic brain accident. Interventions were analyzed
      against the background of the different speculations about the relationship
      between filamentary keratopathy and the vegetative state. RESULTS: Both patients'
      medical records registered 36 and 24 episodes of "a red eye," respectively, which
      in most cases were due to filamentary keratopathy. The episodes lasted 1-5(1/2)
      months, despite lubrication, removal of filaments, and regular application of
      corticoid ointment. The longest remission occurred when the eyes were frequently
      opened, and no topical medications were applied. This experience supports the
      hypothesis that prolonged eyelid closure is more likely related to filamentary
      keratopathy in these patients, more so than a moistening disturbance.
      CONCLUSIONS: Filamentary keratopathy can be a chronic problem in the long-term
      course of a patient in a vegetative state with remissions and exacerbations.
      These cases substantiate a relationship, although the precise mechanism is
      speculative. The incidence and effective treatment await further reports.

PMID- 15968173
TI  - In vivo microstructural analysis of the cornea in Maroteaux-Lamy syndrome.
AB  - PURPOSE: This report describes the clinical and in vivo microstructural features
      of the cornea in a case of Maroteaux-Lamy syndrome. METHODS: A 17-year-old female
      with Maroteaux-Lamy syndrome was examined by slit-lamp biomicroscopy, Orbscan II
      slit-scanning elevation topography, and in vivo confocal microscopy. RESULTS:
      Slit-lamp biomicroscopy revealed bilateral, altered corneal transparency
      involving the posterior half of the stroma. Funduscopy revealed bilateral small,
      crowded optic discs, and radial macula retinal folds. On in vivo confocal
      microscopy, the middle and posterior stroma were clearly visualized and exhibited
      well-defined, unusually shaped keratocytes. These cells contained single or
      multiple hyporeflective regions with well-defined borders that ranged from 1 to
      11.6 microm in diameter. These abnormal keratocytes were particularly abundant in
      the posterior stroma and sparse in the anterior stroma. CONCLUSIONS: This is the
      first case of Maroteaux-Lamy syndrome in which altered corneal transparency has
      been imaged by in vivo confocal microscopy and macula retinal folds have been
      described.

PMID- 15968174
TI  - Infectious keratitis after astigmatic keratotomy in penetrating keratoplasty:
      review of three cases.
AB  - PURPOSE: To present 3 cases in 2 patients of infectious keratitis of the
      astigmatic keratotomy (AK) site in patients who had previous penetrating
      keratoplasty. METHODS: History, clinical examination, chart review, cultures, and
      laboratory results were obtained from 2 patients with infectious keratitis within
      the donor stroma of their graft after an AK was performed. RESULTS: One patient
      had an early infiltrate of the AK site that was culture negative. This cleared
      with fortified antibiotics, and the patient had a final visual acuity of 20/30-2.
      The second patient developed 2 late infections, the first with coagulase negative
      Staphylococcus and the second infection with Pseudomonas aeruginosa. Both of
      these infections cleared with fortified antibiotics, and the final visual acuity
      was 20/25. Neither patient developed a rejection episode from the infections, and
      both grafts survived. CONCLUSIONS: We report a series of 3 cases of infectious
      keratitis in 2 patients after AKs in corneal grafts. This, to the best of our
      knowledge, has not been previously reported. Patients who suffer infectious
      keratitis after AK in corneal grafts may have good visual outcomes if managed
      with appropriate antibiotic regimens and closely followed.

PMID- 15968175
TI  - Intraocular lens calculation in a patient with previous penetrating keratoplasty
      and LASIK.
AB  - PURPOSE: To report a case of a patient who underwent cataract extraction with
      intraocular lens (IOL) implantation after previous penetrating keratoplasty (PK)
      followed by laser in situ keratomileusis (LASIK). METHODS: Case report and
      literature review of cataract surgery after PK and LASIK. Cataract surgery was
      successfully performed in a patient with previous PK and LASIK. This paper
      outlines our method of calculating the correct power IOL for implant. RESULTS:
      The patient's 1-month postoperative uncorrected visual acuity was 20/70 and best
      spectacle-corrected visual acuity was 20/30+ with -0.75 +0.50 x 180. CONCLUSIONS:
      We report the case of a patient with cataract extraction with IOL implantation
      after PK and LASIK as well as a description of the method used to calculate IOL
      power after PK and LASIK. While the IOL selection can be difficult, using the
      appropriate nomogram can result in good visual outcomes.

PMID- 15968176
TI  - Dendritic keratopathy in ocular rosacea.
AB  - PURPOSE: To report a case of dendritic keratopathy secondary to ocular rosacea in
      a 62-year-old man. METHOD: Case report. RESULTS: We discuss the ophthalmologic
      findings, management, and course in a patient with an unusual dendritic corneal
      lesion resistant to medical therapy. Other causes of dendritic lesions on the
      cornea were ruled out after investigation. The patient experienced symptomatic
      and objective improvement in the lesion with treatment of ocular rosacea.
      CONCLUSION: This case represents an interesting presentation of rosacea with
      dendritic keratopathy associated with typical skin lesions.

PMID- 15968179
TI  - All on the same page.

PMID- 15968178
TI  - Clinicopathologic study of conjunctivochalasis.

PMID- 15968180
TI  - Branding your practice.

PMID- 15968181
TI  - A positive correlation between occlusal trauma and peri-implant bone loss:
      literature support.
AB  - The relationship between occlusal overload and peri-implant bone loss remains a
      controversial topic in implant dentistry. A causal relationship between the
      incidence of marginal bone loss next to an implant and occlusal overload implies
      a treatment plan and occlusal scheme would benefit from a force management
      approach. A MEDLINE-assisted and hand search of peer-reviewed English literature
      and relative textbooks were used for a selective review of articles addressing
      biomechanical stress and bone loss in cellular biomechanics, engineering
      principles, mechanical properties of bone, animal studies, clinical reports, bone
      physiology, and implant design biomechanics. These papers demonstrate occlusal
      overload on implants may increase the incidence of marginal bone loss.

PMID- 15968182
TI  - Critical hemorrhage in the floor of the mouth during implant placement in the
      first mandibular premolar position: a case report.
AB  - Although dental implantation is considered to be a safe surgical procedure, this
      report focuses on a critical hemorrhaging episode associated with implant
      placement in the first mandibular premolar position. Excessive bleeding and
      formation of massive lingual, sublingual, and submandibular hematomas were the
      result of arterial trauma that occurred during the osteotomy preparation. The
      vascular injury was induced through a perforation of the lingual mandibular
      cortex. Critical bleeding was conservatively controlled and the case was further
      handled efficiently with an expectant airway management in a hospital
      environment. Similar case reports are reviewed in an attempt to draw attention to
      this rare but potentially life-endangering risk of implant dentistry. Common
      causes of severe hemorrhage in the floor of the mouth, anatomical considerations,
      bleeding control measures, and related airway issues are also discussed.

PMID- 15968183
TI  - Single-tooth implant restorations: a retrospective study.
AB  - Single-tooth implant restorations are a demanding clinical endeavor. Predictable
      results can be achieved when clinicians adhere to a recommended protocol for
      placement and reconstruction. As the demand to use implants to replace single
      missing teeth increased, so did the demand for superior esthetic outcome and
      immediate insertion and loading. The present study presents a 6-year audit of
      single-tooth implant restorations at Riyadh Dental Centre with a survival
      probability of 93.8% after a 5-year period. The recent trend of immediate
      insertion and loading results was also encouraging but still needs technical
      refinement as well as long-term follow-up review between different protocols.

PMID- 15968184
TI  - Surgical success of intraoral autogenous block onlay bone grafting for alveolar
      ridge augmentation.
AB  - This article evaluates the surgical success of alveolar bone augmentation using
      intraoral block bone graft prior to dental implantation and measures the amount
      of bone accumulation using this technique. A consecutive retrospective study was
      conducted on patients who had onlay bone grafts from 1999 to 2001. Files of 56
      healthy patients reporting 64 bone graft operations were reviewed. Medical
      history, smoking status, area of surgery, bone origin (donor sites) and
      complications were recorded. Panoramic and tomographic radiographs were measured
      for the vertical and horizontal bone addition and mesiodistal dimension of the
      graft. Graft exposure or/and graft removal were defined as failure; hematoma,
      swelling, inflammation, or temporary paresthesia were defined as complications.
      The average vertical addition was 5.6 mm measured from the bottom of the vertical
      lesion before bone grafting to the top of the graft. The average faciolingual
      addition was 3.8 mm. The mesiodistal graft length ranged from 4 mm to 67 mm
      (average 15.2 mm). According to our criteria, 56 (87.5%) of the 64 bone grafts
      were successful, 46 (71.9%) were totally uneventful, and 10 (15.6%) had
      complications. Smoking and diabetes were associated with a high rate of
      complications and graft failure. More complications were observed in the vertical
      than in the horizontal bone grafts. Intraoral bone block graft is a predictable
      operation with high success rates that provides faciolingual and vertical bone
      addition. Onlay bone grafting has a low rate of complications and failures.
      Intraoral bone graft should not be recommended for diabetic patients and smokers.

PMID- 15968185
TI  - Localized ridge augmentation with allogenic block grafts prior to implant
      placement: case reports and histologic evaluations.
AB  - The placement of dental implants is based on the amount of alveolar bone present
      in the edentulous site to be reconstructed. Insufficient alveolar contours may
      require bone grafting procedures to restore an adequate bone volume before
      implant placement. Larger osseous defects often require block grafts harvested
      from the symphysis or the ramus buccal shelf region. These provide adequate donor
      sites to harvest a graft sufficient to restore a significant defect in the
      osseous structures planned for implant placements. Autogenous block grafts have
      been well established to reconstruct these types of defects prior to implant
      placement procedures. However, surgical complications associated with the
      unfavorable anatomical structures and the necessity of large donor sites (e.g.,
      symphysis and ramus buccal shelf) have led to the use of allogenic grafting
      materials. Recent developments in allogenic grafting materials have lead to the
      development of a corticocancellous block graft harvested from the iliac crest
      region. This study evaluates the clinical indications of these allogenic graft
      materials to replace compromised alveolar bone defects both horizontal and
      vertical in nature. The analysis is supported by re-entry procedures and
      histologic evaluations to substantiate predictability.

PMID- 15968186
TI  - Clinical assessment of 40 patients subjected to alveolar distraction
      osteogenesis.
AB  - Alveolar bone distraction is a technique used to restore vertical defects in the
      edentulous alveolar ridge. The gradual growth of bone tissue has a predictable
      result, allowing the placement of an osseointegrated implant in an ideal
      position. In this study, the effectiveness of the alveolar distraction technique
      was verified, using an extraosseous device. The bone augmentation average was 9.5
      mm in 40 patients, showing a 92.5% success rate.

PMID- 15968187
TI  - Reducing the risk of failure during intra-oral bone grafting.
AB  - The small size of the intra-oral bone grafts can increase the handling problems
      during the handling of the graft before final securing to the recipient site. A
      technique is described whereby the risk element during this phase of the
      procedure can be reduced. By securing the bone graft to the handle of an artery
      forceps using a length of ligature, the graft can be handled safely. It can also
      be held in the desired final position during preparation of the screw hole. The
      ligature is released only after the graft has been secured by engagement of the
      retaining screws.

PMID- 15968189
TI  - Stress distribution in bone: single-unit implant prostheses veneered with
      porcelain or a new composite material.
AB  - The purpose of this study was to simulate dynamic and static occlusal loading on
      one unit fixed, implant-supported prostheses veneered with porcelain and with
      GRADIA in a 3-dimensional finite element model of the human mandible to analyze
      and compare the resultant stresses in the superstructures and in the supporting
      bone. Calculation and visualization of stress, deformation, and displacement of
      complex structures under simulated forces were evaluated by finite element
      analysis (FEA) using ANSYS. The device employed was from the OSTEOFIX Dental
      Implant System (Oulu, Finland), and the veneering materials used were standard
      dental porcelain and GC GRADIA (Tokyo, Japan), a new composite material. Two
      different loading conditions were considered: static and transitional or impact,
      each delivered in three different directions: horizontal (Fh) at 0 degrees ,
      vertical (Fv) at 90 degrees , and oblique (Fo) at 120 degrees . The proportion of
      the force: magnitude was fh:fv:fo = 1:3.5:7. A vertical load of 500 N, a
      horizontal load of 143 N, and an oblique load of 1000 N were applied. The results
      showed that the highest stresses in the bone-implant interface occurred in the
      region of cortical bone adjacent to the first thread of implants in all models
      and varied within 6.5%. Maximum stresses and displacements were higher (7%) in
      those models with statically loaded implants as compared with those that had been
      dynamically loading. The direction of loading played a major role in determining
      stress levels and they varied at up to 85%. It was shown that with dynamic loads,
      the peak of 1.568 mm was registered in the model with the GRADIA veneering
      material. This displacement was 6.5% higher than that found with the Vita VMK 68
      veneers. These results suggest that the implant superstructure-fixed single crown
      veneering materials-porcelain and GRADIA played minor influences to the
      displacements and stresses in the implant supported bone with a 1% variance. One
      of the reasons for this element resulting in so minor a contribution to stress
      relief was the relatively small volume of the veneers as compared with the far
      greater volume and stiffness of the superstructures and implants. One of the
      advantages of GC GRADIA is that it reduces impact force under dynamic load up to
      a 6.5%.

PMID- 15968188
TI  - Strain situation after fixation of three-unit ceramic veneered implant
      superstructures.
AB  - The passive fit of superstructures used in implant prosthodontics is affected by
      several variables. The objective of this study was to quantify the strain
      development in various fixed partial dentures (FPDs), both in the condition as
      cast and after ceramic veneering. Five different types of three-unit FPDs
      (cementable/repositioning technique impression; cementable/pick-up technique
      impression; screw-retained/plastic cylinder; screw-retained/gold cylinder; screw
      retained/bonded) with 10 samples each, representing commonly used FPD-types, were
      investigated before and after ceramic veneering. Two ITI implants were anchored
      in a measurement model simulating a real-life patient situation and strain gauges
      were mounted close to the implants. The strain development was recorded during
      cement setting and screw fixation. For statistical analysis, multivariate two
      sample tests were performed with the level of significance set at P = 0.1. All
      FPDs revealed measurable amounts of strain. Neither the impression technique nor
      the fabrication modes for conventional screw-retained FPDs had a significant
      influence on strain development. Ceramic veneering caused an increase in strain
      development for the conventional bridge types. Furthermore, cementing appears to
      be able to compensate fabrication inaccuracies better than screw retention. The
      lowest strains were found in FPDs bonded to gold cylinders on the measurement
      model for metal frames and ceramic-veneered FPDs. Conventional procedures are
      unable to produce superstructures with an absolute passive fit. The technique of
      bonding superstructures to prefabricated components in the oral cavity seems to
      compensate for various shortcomings in superstructure fabrication.

PMID- 15968190
TI  - Acellular dermal matrix and hydroxyapatite in prevention of ridge deformities
      after tooth extraction.
AB  - The aim of this study was to evaluate the role of acellular dermal matrix graft
      (ADMG) acting as a membrane, associated with a resorbable hydroxyapatite (RHA) in
      bone regeneration to prevent ridge deformities after tooth extraction. Fifteen
      patients who had at least 2 noncontiguous, uniradicular teeth indicated for
      extraction were selected. In group I, the extraction sockets were covered by ADMG
      alone; and in group II, the alveoli were filled with RHA before the placement of
      the ADMG. After 6 months, re-entry surgeries and biopsies were performed.
      Although ridge thickness had been preserved in both groups, the means were
      significantly greater (P < 0.05) for group II when compared to group I (6,8 +/-
      1.26 and 5.53 +/- 1.06). The histologic analysis showed small bone formation in
      some samples for group II, where the presence of a highly vascularized fibrous
      connective tissue surrounding the particles was a common finding. Based on the
      results, it can be concluded that the ADMG was able to preserve ridge thickness
      and that the additional use of RHA favored the preservation of the ridges along
      with an increase in the width of keratinized tissue.

PMID- 15968191
TI  - Maxillary sinus augmentation using a peptide-modified graft material in three
      mixtures: a prospective human case series of histologic and histomorphometric
      results.
AB  - This prospective study assessed vital bone quality and quantity after grafting
      maxillary sinuses with anorganic bone mineral containing a cell binding peptide
      (ABM/P-15) in combination with DFDBA (Mix I), hydrogel/ABM/P-15 (Mix II), or PRP
      (Mix III). Fifteen maxillary sinuses in 12 patients were grafted with the ABM/P
      15 mixtures and after 4 to 5 months, cores were taken and analyzed histologically
      and histomorphometrically. Fifty-nine screw-type implants were placed. Mixes
      containing a spacer material (Mix I and II) produced greater average vital bone,
      more mature bone, and more interconnected bone bridges from the cortical (oral)
      end to the most apical portion, compared to a mix that lacked a spacer material
      (Mix III). None of the 59 implants failed with any graft material up to 5 months
      following implant placement. The study demonstrates that new trabecular bone is
      formed after grafting ABM/P-15 in the sinus floor; that more vital bone is formed
      when ABM/P-15 is mixed with a spacer material than without; and that implants can
      be successfully placed.

PMID- 15968192
TI  - Detection of implant crevicular fluid prostaglandin E2 levels for the assessment
      of peri-implant health: a pilot study.
AB  - Inflammatory changes in the peri-implant tissues may lead to peri-implantitis and
      bone loss. Prostaglandin E2 has been shown to have proinflammatory effects on
      peri-implant tissues, including mediation of bone resorption. The aim of this
      study was to assess prostaglandin E2 levels in implant crevicular fluid and the
      possibility of using this method in diagnosing peri-implant mucositis. Twenty
      four dental implants with 3 mm or greater probing depths comprised the test group
      and another 24 implants with probing depths less than 3 mm served as the control
      group. Plaque index (PI), gingival index (GI), and probing pocket depths (PPD)
      were recorded. Implant crevicular fluid was obtained by collection onto
      periopapers. Then, prostaglandin E2 levels were evaluated using a commercially
      available enzyme immuno-assay kit. PI, GI, PPD, and implant crevicular fluid
      (ICF) levels of prostaglandin E2 were found to be statistically significantly
      higher in the test group (P < 0.05). In the test group, gingival index and
      probing depths were found to be statistically significantly related with ICF
      prostaglandin E2 levels (P < 0.05). In the control group, there was no
      statistically significant positive correlation between clinical parameters and
      ICF prostaglandin E2 levels (P > 0.05). It may be speculated that biochemical
      tests, such as the detection of prostaglandin E2 levels in the crevicular fluid
      are useful diagnostic methods for the maintenance of functional dental implants.

PMID- 15968193
TI  - Factors associated with implant recommendation for single-tooth replacement.
AB  - The use of dental implants for single-tooth replacement has been established as a
      predictable treatment option; yet, limited data are available as to how
      frequently this option is recommended to patients. The aim of the present study
      was to examine the frequency of implant recommendation by general dental
      practitioners after single-tooth extraction and factors influencing their
      decision to recommend an implant. All single-tooth extractions performed in 26
      general dental practice clinics in Kuwait over a 30-day period were examined.
      Dentists in these centers used the study form to record demographic data, the
      type of tooth extracted, reason for extraction, and replacement options presented
      to the patients. Univariate and logistic regression analyses were used to examine
      associations between background factors and decisions to recommend implant
      therapy. A total of 1367 patients (mean age, 37.9 +/- 11.8 years) had an
      extraction of one tooth during the study period. Forty-three patients were
      offered implants as a replacement option (3.3% of the total sample; 8.6% of
      patients who were offered tooth replacement options). Factors associated
      significantly with the recommendation of an implant by Kuwaiti dentists to their
      patients included younger age, regular dental maintenance visits, and adequate
      oral hygiene practices (P < 0.05; binary logistic regression). Dental implant
      recommendation for single-tooth replacement in the present sample of dentists was
      low. Factors associated significantly with dentist recommendation of an implant
      for single-tooth replacement included age, history of dental maintenance, and
      oral hygiene practices.

PMID- 15968194
TI  - Aggressive behavior of stage I ovarian mucinous tumors lacking extensive
      infiltrative invasion: a report of four cases and review of the literature.
AB  - Previous studies have indicated that mucinous carcinomas of the ovary associated
      with extraovarian spread at the time of presentation or follow-up almost always
      have extensive infiltrative invasion within the primary tumor. We present four
      cases of stage I ovarian mucinous tumors that lacked extensive infiltrative
      invasion but were associated with an unexpectedly aggressive behavior. The
      patients were 18, 20, 41, and 45 years of age at presentation. All four of them
      presented with an abdominal mass or increased abdominal girth. The tumors were
      all stage Ia, 17 to 37 centimeters in maximal dimension, and typically
      multicystic with solid areas. The number of blocks per centimeter of tumor
      diameter was 0.65, 0.88, 0.92, and 1.0 in the four tumors, respectively, a degree
      of sampling within that recommended in previous studies. Clinical findings
      supported that they were primary tumors rather than metastatic from an occult
      primary tumor. On microscopic examination, the tumors all contained foci of
      intraepithelial carcinoma and foci of invasion as follows: expansile invasion
      only (two cases), expansile invasion and microinvasive carcinoma (one case), and
      microinvasive carcinoma only (one case). The expansile invasion was extensive in
      each of the three cases in which it was present. On follow-up, each patient
      experienced recurrent disease 7 months to 4.5 years after diagnosis, including
      hematogenous spread to lung and/or bone and liver in three patients. Three of
      four patients developed intraperitoneal spread. Three of four patients died of
      disease, and one patient is alive with persistent disease. Although ovarian
      mucinous tumors with only expansile invasion or only microinvasive carcinoma are
      usually associated with an excellent prognosis, this study indicates that these
      tumors can rarely behave in an aggressive fashion with hematogenous spread and a
      fatal outcome. Some of these tumors may have contained unsampled foci of
      infiltrative invasion. Although the optimum level of sampling in mucinous tumors
      remains to be determined, we recommend additional sampling of tumors in which the
      initial sections reveal intraepithelial carcinoma, microinvasive carcinoma,
      expansile invasion, or combinations thereof.

PMID- 15968195
TI  - Primary retroperitoneal mucinous cystadenoma of borderline malignancy: a case
      report and review of the literature.
AB  - A case of primary retroperitoneal mucinous cystic tumor of borderline malignancy
      is reported. A 36-year-old, nulliparous woman complained of abdominal fullness.
      Physical examination revealed a cystic mass 12-cm x 8-cm in size. At laparotomy,
      a cystic tumor was observed in the right retroperitoneal space. Both ovaries
      appeared normal and the uterus was almost normal except for small myomatous
      nodules. Removal of the retroperitoneal tumor, an appendectomy, and a myomectomy
      were performed. The histologic diagnosis was a primary retroperitoneal mucinous
      cystic tumor of borderline malignancy, similar to findings for ovarian tumor.
      There was no evidence of disease 6 months after the surgery.

PMID- 15968196
TI  - Combined adult granulosa cell tumor and mucinous cystadenoma of the ovary:
      granulosa cell tumor with heterologous mucinous elements.
AB  - We describe an unusual ovarian neoplasm in a 57-year-old woman composed of an
      admixture of mucinous cystadenoma and adult granulosa cell tumor (AGCT). In areas
      the two components were separate but elsewhere there was intermingling of the two
      elements. The combination of mucinous cystadenoma and AGCT has only rarely been
      reported. Theories of histogenesis include a collision tumor and heterologous
      mucinous differentiation within an AGCT. We favor the latter theory in this case,
      because in many areas there was an intimate admixture of the two components.
      Because heterologous mucinous elements are well described in other ovarian sex
      cord-stromal neoplasms, especially but not exclusively Sertoli Leydig cell
      tumors, it is not unexpected that a similar phenomenon could occur in an AGCT. We
      review the previously reported cases of combined mucinous cystadenoma and
      granulosa cell tumor of the ovary.

PMID- 15968197
TI  - The impact of c-kit and ki-67 expression on patients prognosis in advanced
      ovarian serous carcinoma.
AB  - The transmembrane-tyrosine-kinase receptor, c-kit, is involved in cell
      differentiation and has been found to be expressed in normal human cell types and
      solid tumors. This study was designed to investigate the effects of c-kit
      expression on: 1) tumor proliferation and apoptosis, and 2) survival in patients
      with high-grade advanced stage ovarian serous carcinoma (OSC). We identified 118
      patients with high-grade advanced stage OSC from our files. Clinical data,
      including demographics and overall survival, were collected. Immunohistochemical
      panel consisting of c-kit, ki-67, p53, and bcl-2 was performed. C-kit was
      categorized as positive if any cytoplasmic or membranous staining pattern was
      identified. Correlation between c-kit expression and the other markers was
      performed. Survival analysis was performed using COX proportional hazards
      regression and Kaplan-Meier test. Of 118 cases, 25 (21.2%) expressed c-kit. Of 93
      c-kit-negative tumors, 87.1% had a high proliferation index. High p53 and bcl-2
      expression was identified in 96 (81.4%) and 59 (50%) cases respectively. No
      significant statistical correlation was identified between c-kit and apoptosis
      markers. Tumors lacking c-kit expression showed a trend toward having high
      proliferation index, but this did not achieve statistical significance (p =
      0.07). Of the seven variables included in the multivariate survival analysis,
      only c-kit (odds ratio, 2.12; 95% confidence interval, 08-4.17; p = 0.02) and ki
      67 (odds ratio, 1.9; 95% confidence interval, 1.1-3.1; p = 0.03) showed an
      independent statistically significant impact on survival. High-grade advanced
      stage OSC lacking c-kit expression correlates with poor outcome. Interestingly,
      cases lacking c-kit expression also showed a trend to have high proliferation
      index.

PMID- 15968198
TI  - Stage IV micropapillary serous ovarian carcinoma: a report of three cases.
AB  - Micropapillary serous carcinomas (MPSCs) have been distinguished from typical
      ovarian serous borderline tumors. Although the clinical features of MPSCs have
      been described in several studies, there is almost no clinicopathologic
      information regarding stage IV MPSC patients. We describe three cases of stage IV
      invasive MPSC with clinical and pathologic findings. One case had an umbilical
      metastasis (Sister Mary Joseph's nodule), and the other two cases had
      cytologically positive pleural effusions. These cases demonstrate the potential
      of MPSCs for aggressive clinical behavior and distant metastases.

PMID- 15968199
TI  - Expression of CD10 and cytokeratins in ovarian and renal clear cell carcinoma.
AB  - A solid pattern of tumor cells with a clear cytoplasm is common to both ovarian
      clear cell carcinoma (OvCCC) and renal clear cell carcinoma (RCCC). This study
      examined the possible differential expression of CD10 and cytokeratins (CK7,
      CK20, 34betaE12, and CAM5.2) between these two types. An immunohistochemical
      technique using peroxidase-labeled amino acid polymers was used to test formalin
      fixed and paraffin-embedded tissues. In OvCCC, 6 of 29 cases were positive for
      CD10, and all cases had expression of CK7, 34betaE12, and CAM5.2. In contrast,
      all 24 RCCC cases had CD10 and CAM5.2 immunoreactivity, but none had any staining
      for 34betaE12. CK7 was only expressed in nine cases. No CK20 positivity was
      observed in any sample from either tumor type. Localization of CD10 expression
      was different in OvCCC versus RCCC. Although positive staining for 34betaE12
      strongly suggests OvCCC, sometimes only a few cells may be stained. Therefore,
      34betaE12-negative biopsies also should be evaluated for CD10 and CK7
      immunoreactivity to enable histologic and cytologic differential diagnosis.

PMID- 15968200
TI  - Survivin expression in endometrial carcinoma: a tissue microarray study with
      correlation with PTEN and STAT-3.
AB  - Evasion of apoptotic cell death plays a key role in cancer development. Survivin
      is a member of the inhibitor of apoptosis proteins, which also has a role in the
      control of cell division. Survivin may be overexpressed in some tumors and has
      been suggested to be related to PTEN, beta-catenin, p53 [all of them frequently
      abnormal in endometrial carcinomas (ECs)], and STAT-3. A tissue microarray was
      constructed from paraffin-embedded blocks of 95 ECs, previously studied for
      microsatellite instability and for alterations in PTEN, k-RAS, and CTNNB-1.
      Immunohistochemical evaluation included 1) survivin, 2) markers of cell
      proliferation and apoptosis (Ki67-MIB1 and M 30-neoepitope cytokeratin 18), and
      3) proteins involved in cell signaling pathways (PTEN, phospho-AKT, beta-catenin,
      p53, and STAT-3). Survivin expression was frequent in ECs (75.95%) but did not
      show any statistical significant correlation with histological type and grade,
      stage, overall survival, or mitotic and apoptotic indexes. Survivin expression
      had a statistical significant correlation with decreased PTEN expression (r = 
      0.383, p = 0.001), increased phospho-AKT (r = 0.70, p < 0.001), and positive STAT
      3 immunostaining (r = 0.6, p < 0.001). Survivin expression did not show
      statistical correlation with either beta-catenin or p53 alterations. The results
      suggest that increased survivin expression is frequent in ECs and may be
      dependent on STAT-3 and PI3 K/AKT activation. Because PTEN abnormalities are very
      frequent in ECs, the results from this study indicate that PTEN may interfere
      with the process of apoptosis and cell proliferation by promoting survivin
      expression.

PMID- 15968201
TI  - Discordance between serum level and tissue immunohistochemical staining of CA125
      in endometrioid adenocarcinoma of the uterine corpus.
AB  - This study was designed to correlate tissue expression of CA125 with the
      corresponding serum value in endometrial cancer. The records of 52 endometrioid
      adenocarcinomas diagnosed were reviewed. Serum CA125 levels were examined before
      definitive surgery, and 20 U/ml was used as the cutoff value. Immunohistochemical
      staining for CA125 was assessed according to the ImmunoReactive Score.
      Statistical analyzes were performed to identify independent factor for high serum
      CA125 levels, including CA125 staining and the conventional pathologic features.
      Elevated serum CA125 levels were found in 15 of 52 patients (29%) (range, 0.1
      172.1; mean 22.6 U/ml). The frequency of positive CA125 tissue staining (35/52,
      67%) tended to be higher than that of elevated serum levels (p = 0.046). Fifteen
      patients with elevated serum CA125 levels statistically differed from the
      remaining 37 patients with normal serum CA125 level with respect to International
      Federation of Gynecology and Obstetrics (FIGO) stage (p = 0.027) and lymph node
      metastasis (p = 0.024), and tended to have positive washing cytology (p = 0.052).
      In multivariate analysis, elevated serum CA125 significantly correlated only with
      FIGO stage III, but not with tumor size or CA125 tissue staining. Intrauterine
      tumor may not be the main source of serum CA125 in endometrial cancer, and
      elevated serum level is closely related to the presence of disseminated cancer
      cells in the peritoneal cavity.

PMID- 15968202
TI  - Overdiagnosis of complete and partial hydatidiform mole in tubal ectopic
      pregnancies.
AB  - Partial or complete hydatidiform mole (HM) affects approximately 1 in 500 to
      1,000 pregnancies. Previous small series suggest that histopathologic diagnosis
      of HM may be difficult in tubal ectopic pregnancies. The histopathology database
      of a regional Trophoblastic Disease Unit was searched to identify cases with a
      referral diagnosis of tubal HM, and the histopathologic findings were reviewed.
      During the study period (1986-2004 inclusive), there were 132 cases. After
      central review by specialist histopathologists, the final diagnosis was ectopic
      partial mole in two, ectopic complete mole in five, and ectopic hydatidiform mole
      (not otherwise specified) in one. The final diagnosis of definite hydatidiform
      mole was made in eight (6%) cases, significantly less than in referred uterine
      curettage specimens, in which approximately 90% have a confirmatory diagnosis of
      HM (Z = 12.9; p < 0.0001). No cases in this series developed persistent
      gestational trophoblastic disease, the human chorionic gonadotropin concentration
      spontaneously returning to normal. Ectopic pregnancies, where managed surgically,
      should be submitted for histopathologic examination; however, the pathologist
      should be aware that the degree of extravillus trophoblastic proliferation may
      appear more florid compared with evacuated uterine products of conception. Molar
      pregnancy should only be diagnosed when strict criteria regarding morphologic
      abnormalities previously described in uterine evacuation material are applied.

PMID- 15968203
TI  - Expression pattern of the activating protein-1 family of transcription factors in
      gestational trophoblastic lesions.
AB  - The human placenta is an endocrine tissue with a unique capacity for rapid, but
      tightly controlled, proliferation and invasion. Gestational trophoblastic
      diseases (GTDs) are placental pathologies with endocrine activity and partially
      malignant potential and include hydatidiform moles, placental site nodules, and
      tumors such as placental site trophoblastic tumor and choriocarcinomas. The
      activating protein-1 (AP-1) family of transcription factors is composed of the
      cellular homologs of the Jun and Fos oncoproteins, which are immediately involved
      in cellular proliferation, differentiation, and invasion processes and in the
      regulation of endocrine genes. The expression pattern of the AP-1 family in the
      normal human placenta has been recently described, where most of the factors were
      found in the extravillous (invasive) trophoblast. Their systematic expression in
      GTD has not been studied thus far. For this reason in this study, we investigated
      the expression pattern of the AP-1 family in GTDs and compared it with the
      expression in normal placenta using immunohistochemistry with specific polyclonal
      antibodies against all members of the AP-1 family (JunB, JunD, c-Jun, c-Fos,
      FosB, Fra-1, Fra-2). Immunohistochemistry was performed on normal human placentas
      (positive control) and on 28 cases of GTD including 7 choriocarcinomas and 21
      hydatidiform moles. In the normal placenta and in hydatidiform molar samples,
      most AP-1 factors (especially c-Jun, JunD, and Fra2) were expressed in the
      intermediate (extravillous) trophoblast. In addition, in molar lesions, strong
      expression was found in trophoblasts proliferating from the surface of villi.
      There was only a weak expression of JunB and Fra2 in small fractions of villous
      cyto- and syncytiotrophoblast nuclei. In choriocarcinomas, there was a strong
      expression for c-Jun, JunD, Fra1, and Fra2. The specific localization to
      extravillous trophoblasts and their expression pattern in GTDs indicate that the
      AP-1 family of transcription factors might be implicated in regulating
      proliferation and invasion of trophoblasts and play a role in the pathogenesis of
      GTDs.

PMID- 15968204
TI  - Osteopontin expression in gestational trophoblastic diseases: correlation with
      expression of the adhesion molecule, CEACAM1.
AB  - The human placenta is a complex tissue with multiple endocrine and nutritional
      functions and a unique capacity for rapid proliferation but tightly controlled
      invasion, differentiating it from malignant tumors. Osteopontin (OPN) is a
      glycoprotein of the extracellular matrix, which has been shown to mediate
      cellular migration and invasion and to contribute to tumorigenesis in several
      types of cancers. OPN also could be implicated in regulating implantation and
      placentation by promoting cellular migration and invasion in a placenta-specific
      fashion. We could demonstrate the expression pattern of OPN in the normal human
      placenta in which it is localized in the extravillous (intermediate) trophoblast
      and the villous cytotrophoblast. CEACAM1 is an adhesion molecule, which we have
      recently found to be expressed at the maternal-fetal interface of the normal
      placenta with a localization to the extravillous (invasive) trophoblast and in
      gestational trophoblastic disease (GTD) and also to be potentially implicated in
      trophoblast invasion and tumorigenesis. Both OPN and CEACAM1 have been shown to
      interact with integrin beta3. The purpose of this study was to investigate the
      expression pattern of OPN in GTD and to correlate it with the expression of
      CEACAM1. To analyze the expression of OPN, we performed immunohistochemistry on a
      total of 27 cases of GTD, including 21 hydatidiform moles and 6 choriocarcinomas,
      which had previously been characterized with respect to their CEACAM1 expression.
      Hydatidiform moles showed a positivity for OPN in villous cytotrophoblast and in
      the trophoblast proliferations on the villous surface. The strongest OPN
      expression could be observed in the choriocarcinomas with a heterogenous OPN
      expression pattern. CEACAM1 had shown similar results and was found to be
      expressed in choriocarcinoma. The expression pattern of osteopontin in
      gestational trophoblastic diseases indicates that it might play a role in the
      pathogenesis of GTD (possibly as a functional complex with CEACAM1 and integrin
      beta3) and might be useful as an additional diagnostic marker for such lesions.

PMID- 15968205
TI  - Clinicopathologic and immunohistochemical differences in complete and partial
      hydatidiform moles in a multiracial Malaysian population.

PMID- 15968207
TI  - Fallopian tube prolapse mimicking aggressive angiomyxoma.
AB  - A 68-year-old woman presented with a 4-cm polypoid bleeding mass protruding from
      the vaginal apex 30 years after vaginal hysterectomy. Laparotomy did not confirm
      the clinical suspicion of bowel prolapse and led to resection of the mass.
      Microscopic examination revealed a hypocellular edematous lesion with glandular
      areas resembling fallopian tube epithelium. Condensation of eosinophilic fibrils
      around medium sized vessels was marked. This case of fallopian tube prolapse
      shows an unusual resemblance of aggressive angiomyxoma and thus poses a
      diagnostic pitfall.

PMID- 15968206
TI  - Expression of proliferating cell nuclear antigen and bcl-2 during a
      pseudomenopausal state induced by presurgical treatment of uterine leiomyomas
      with gonadotropin-releasing hormone analogues plus tibolone.

PMID- 15968208
TI  - Absence of human papillomavirus infection in minimal deviation adenocarcinoma and
      lobular endocervical glandular hyperplasia.
AB  - The human papillomavirus (HPV) is basically always detected in squamous cell
      carcinoma of the cervix and its precursors; a high incidence of HPV also has been
      reported in adenocarcinoma and adenocarcinoma in situ of the uterine cervix.
      Lobular endocervical glandular hyperplasia (LEGH) was first described by Nucci in
      1999. It is difficult to differentiate minimal deviation adenocarcinoma (MDA)
      from LEGH preoperatively or postoperatively by clinical and pathologic features.
      The relationships between HPV and MDA or LEGH have not been studied well because
      of the rare incidence of the two diseases. To our knowledge, the HPV status in
      LEGH has not been reported. This study was designed to investigate HPV infection
      in MDA and LEGH, using the polymerase chain reaction (PCR) technique. Tumor
      tissue lesions were microdissected and the detection of HPV and its typing were
      analyzed by PCR-based assay. As the control, HPV DNA was detected in all cases of
      squamous cell carcinoma and three of five cases of adenocarcinoma. However, no
      HPV DNA was detected in any of the 10 cases of LEGH or in the 3 cases of MDA.
      These results suggest that MDA and LEGH are probably not related to HPV
      infection.

PMID- 15968209
TI  - Vulvar acantholytic squamous carcinoma: a case report with immunohistochemical
      and molecular study.
AB  - Acantholytic carcinoma is a subtype of squamous carcinoma, characterized by
      tubular and alveolar formations as a consequence of the acantholysis. We report a
      case of vulvar squamous acantholytic carcinoma (VSAC) in a 69-year-old woman, who
      was admitted to our institution for vulvar pruritus and the presence of a large,
      bilateral, exophytic, and ulcerated lesion, measuring 7 x 8 cm. The patient had
      never received vulvar or pelvic radiation therapy. Pathological examination with
      an immunohistochemical study showed features of VSAC and high p16 protein
      expression. Molecular study by polymerase chain reaction amplification of DNA
      tumor revealed a weakly positive signal for human papillomavirus. In conclusion,
      our case, which is the first case of VSAC with polymerase chain reaction analysis
      and immunohistochemical expression of p16 protein, suggested that this neoplasm
      could be related to human papillomavirus infection.

PMID- 15968212
TI  - Managing elders with comorbidities.
AB  - Carle's Medicare Coordinated Care Demonstration care/disease management
      interventional components, based on the chronic care model, are described for
      elderly patients in 13 counties in Illinois. Patients enrolled in the program are
      diagnosed with chronic obstructive pulmonary disease, coronary artery disease,
      diabetes, atrial fibrillation, or congestive heart failure. Primary care teams
      are made up of a primary care physician, an advanced practice nurse, a nurse case
      manager, and a case assistant. The patient/family is the cornerstone of the
      intervention, which is evaluated using a prospective, longitudinal randomized
      treatment-control design.

PMID- 15968213
TI  - Organizational technologies of chronic disease management programs in large rural
      multispecialty group practice systems.
AB  - Four large rural multispecialty group practice systems employ a mix of
      organizational technologies to provide chronic disease management with measurable
      impacts on their patient populations and costs. Four technologies-administrative,
      clinical, information, and social-are proposed as key dimensions for examining
      disease management programs. The benefits of disease management are recognized by
      these systems despite marked variability in the organization of the programs.
      Committees spanning health plans and clinics in the 4 systems and electronic
      medical records and/or other disease management information systems are important
      coordinating mechanisms. Increased reliance on nurses for patient education and
      care coordination in all 4 systems reflects significant extension of clinical and
      social technologies in the management of patient care. The promise of disease
      management as offered by these systems and other auspices are considered.

PMID- 15968214
TI  - Enhancing efficiency and quality of ambulatory care through telehealth
      technology.
AB  - Technology has made great strides in healthcare, but has been slow in reaching a
      Senior's home or residence. At 35 million and growing, the Senior population is
      making it known that home is where they want to stay. Technology advancements in
      devices, communications, and wireless capability are now making possible the
      delivery of customized telehealth solutions to provide Seniors with "enabled
      independence," allowing them to confidently "age in place" at home or residence
      for much longer, with improved health outcomes and quality of life. Combined with
      traditional ambulatory care services, integrating telehealth technology services
      now allows delivery of "virtual assisted living" services at home that can more
      efficiently meet Senior health requirements, and can simplify other aspects of a
      Senior's life that can play a role in extending time at home. To be successful,
      an integrated service must be able to usefully address a range of activities of
      daily living-instrumental activities of daily living, and enhanced activities of
      daily living-requirements. Already proven in other areas such as radiology,
      intensive care units, prisons, and rural communities, companies are working to
      develop practical telehealth service offerings designed for the home or
      residence. These services must be (a) packaged to meet individual Senior needs
      and (b) reviewed and revised regularly to match changes in Senior requirements
      over time. A core element of this service is the use of regular "virtual visits"
      between healthcare professionals and a Senior at home or residence, which have
      been shown to both increase efficiency and Senior health outcomes. Another
      important element is centralizing key data from the telehealth technology into a
      single database to improve information delivered to a Senior's doctor, family,
      and other ambulatory care providers. North Shore eCare and other companies are
      conducting extensive market tests and pilot efforts to make sure service
      offerings meet Senior needs, and can be delivered cost-effectively.

PMID- 15968215
TI  - Health services utilization of a care coordination/home-telehealth program for
      veterans with diabetes: a matched-cohort study.
AB  - This study examined the effectiveness of a veterans affairs (VA) patient-centered
      care coordination/home-telehealth (CC/HT) program as an adjunct to treatment for
      veterans with diabetes. Using an adapted version of the Chronic Care Model, we
      analyzed the differences in healthcare service use between a cohort of 400
      veterans with diabetes who were enrolled in a VA CC/HT program and a matched
      comparison cohort of 400 veterans with diabetes who received no CC/HT
      intervention. Propensity scores were used to improve the balance between the
      treatment and comparison groups. Service use outcomes were assessed at 12 months
      before and after enrollment. A difference-in-differences approach was used in the
      multivariate models to assess the treatment effect for patients in the CC/HT
      programs. Twelve months after enrollment, there was a significant difference
      between the treatment and comparison groups in terms of need-based primary care
      visits (newly scheduled visits that enable the veteran to be seen "just in time,"
      where the health status is monitored and met before health deteriorates),
      increasing in the treatment group and decreasing in the comparison group (P <
      .01). In a subgroup analysis, where we were able to control for the patients' Hb
      A1c values, we found that the treatment group had a lower likelihood of having 1
      or more hospitalizations than patients in the comparison group. Our findings have
      implications for management in that the CC/HT program appears to improve the
      ability of older veterans with diabetes to receive appropriate, timely care,
      thereby improving the quality of care for them and making more efficient use of
      VA healthcare resources.

PMID- 15968216
TI  - The impact of primary care resources on prevention practices.
AB  - Organizational factors influence the quality of preventive care. Combining
      facility-level data from a national organizational survey and centrally
      available, externally abstracted chart review data on prevention performance, we
      assessed the relationship between structural features of primary care departments
      and the quality of preventive care delivered. Primary care practice resources
      were significantly and positively associated with the delivery of 6 of 9
      preventive services. Adjusting for facility size and academic affiliation, these
      resource arrangements accounted for substantial variation in 8 of 9 services.
      Assuring high-quality prevention performance requires ongoing investment in
      primary care-based infrastructure.

PMID- 15968217
TI  - A method for analyzing the financial viability of a rural provider-based
      geriatric clinic.
AB  - Little is known about the financial impact of rural provider-based geriatric
      outpatient clinics on their parent hospitals since the implementation of the
      outpatient prospective payment system. In this study, systems theory was used to
      develop a methodology for determining the financial viability of one such clinic
      in a rural hospital using data commonly found in rural hospital financial
      systems. Formulas were developed to identify the overall financial viability and
      a case-study model was utilized to test the formulas; however, this hospital did
      not track a key data element, resulting in an incomplete analysis.

PMID- 15968218
TI  - Introduction: papers from the Veterans Health Study.

PMID- 15968219
TI  - Assessment of long-term complications due to type 2 diabetes using patient self
      report: the diabetes complications index.
AB  - This study aims to develop a patient-based measure of the complications of type 2
      diabetes that can be used in examining its relationship with health-related
      quality of life (HRQOL) and utilization of health services. Using questions
      analogous to those typically employed by clinicians, we developed a 17-item
      questionnaire to identify prior diagnoses and current symptoms of 6 common
      complications of type 2 diabetes. We administered it to 419 patients with type 2
      diabetes who were part of the Veterans Health Study, a larger prospective
      investigation of veterans receiving ambulatory care. From the responses, we
      calculated a simple sum of the 6 complications. We examined the correlation of
      this Diabetes Complications Index (DCI) with use of diabetes-related medical
      resources, outpatient doctor visits, HRQOL, duration of diabetes, and the degree
      to which patients perceived their health to be diminished by diabetes. The DCI
      was significantly correlated with the degree to which patients perceived their
      health to be diminished by diabetes (r = 0.35, P = .0001), utilization of
      diabetes-related resources (model R = 0.15, P = .0001), outpatient doctor visits
      (model R = .08, P = .001), and duration of diabetes (r = 0.11, P = .04). It had a
      good correlation with aspects of HRQOL that reflect physical function when
      controlling for age and comorbid conditions (model R = 0.23, P = .0001). The DCI
      shows promise as an efficient method for assessing the effects of type 2 diabetes
      on HRQOL and predicting utilization of medical resources.

PMID- 15968220
TI  - Patient-based measures of illness severity in the Veterans Health Study.
AB  - The Veterans Health Study (VHS) was designed to produce patient-based measures of
      health status suitable for monitoring the health of men served by the Veterans
      Health Administration. This article summarizes the objectives, conceptual
      framework, and results of 6 substudies of the VHS that were designed to develop
      disease-focused measures of illness severity, that is, patient-perceived,
      clinically significant manifestations of disease processes that are associated
      with decrements in health-related quality of life. Developmental psychometric
      studies used cross-sectional survey data from the baseline comprehensive
      evaluations conducted in the VHS. Patients who screened positive for the 6 study
      medical conditions in the VHS (osteoarthritis of the knee, n = 511; type 2
      diabetes, n = 425; chronic lung disease, n = 352; hypertension, n = 996; chronic
      low-back pain, n = 574; and alcohol-related disorder, n = 175) were administered
      structured interview modules that assessed symptoms and complications of these
      chronic diseases. Psychometric analyses were conducted to identify internally
      coherent and reliable indices, which were validated with respect to their
      correlations with measures of health-related quality of life (eg, Short Form-36)
      and the utilization of health services. We constructed 6 indices of illness
      severity. The severities of osteoarthritis of the knee and chronic lung disease
      were defined by brief (12 and 6 items, respectively) assessments of symptoms (eg,
      knee pain and dyspnea). Since diabetes and hypertension are largely asymptomatic,
      illness severity for these conditions was assessed by ascertaining complications
      such as angina and vascular disorders. Alcohol-related disorder, which involves
      both behavioral symptoms and physical complications, was assessed by separate
      scales for these 2 dimensions of its severity. Chronic low-back pain required a
      unique solution. Rather than assessing the intensity of back pain, it is more
      productive to construct a measure that focuses on manifestations of
      radiculopathy, that is, whether back pain radiated down the leg to below the
      knee. The 5 symptoms or complication indices and the assessment of radiculopathy
      in chronic low-back pain were significantly correlated with Short Form-36 scores
      and intensity of recent use of health services. The 6 measures may complement
      measures of health-related quality of life in providing more comprehensive
      assessments of health status in Veterans Affairs patients.

PMID- 15968221
TI  - Injection drug use, global HIV/AIDS, and human rights.

PMID- 15968222
TI  - Wisdom from teachers.

PMID- 15968223
TI  - Placebo use.

PMID- 15968224
TI  - Twin study of the longitudinal course of ADHD.

PMID- 15968227
TI  - "Wild child" and declarative memory.

PMID- 15968228
TI  - Attitudes toward suicide and help-seeking in Hungarian adolescents.

PMID- 15968229
TI  - Glucose abnormalities in a non-psychotic patient treated with risperidone.

PMID- 15968230
TI  - Near-death experiences with meningococcal disease.

PMID- 15968231
TI  - A comparison of short- and long-term family therapy for adolescent anorexia
      nervosa.
AB  - OBJECTIVE: Research suggests that family treatment for adolescents with anorexia
      nervosa may be effective. This study was designed to determine the optimal length
      of such family therapy. METHOD: Eighty-six adolescents (12-18 years of age)
      diagnosed with anorexia nervosa were allocated at random to either a short-term
      (10 sessions over 6 months) or long-term treatment (20 sessions over 12 months)
      and evaluated at the end of 1 year using the Eating Disorder Examination (EDE)
      between 1999 and 2002. RESULTS: Although adequately powered to detect differences
      between treatment groups, an intent-to-treat analysis found no significant
      differences between the short-term and long-term treatment groups. Although a
      nonsignificant finding does not prove the null hypothesis, in no instance does
      the confidence interval on the effect size on the difference between the groups
      approach a moderate .5 level. However, post hoc analyses suggest that subjects
      with severe eating-related obsessive-compulsive features or who come from
      nonintact families respond better to long-term treatment. CONCLUSIONS: A short
      term course of family therapy appears to be as effective as a long-term course
      for adolescents with short-duration anorexia nervosa. However, there is a
      suggestion that those with more severe eating-related obsessive-compulsive
      thinking and nonintact families benefit from longer treatment.

PMID- 15968232
TI  - A randomized, double-blind, placebo-controlled trial of metoclopramide for the
      treatment of Tourette's disorder.
AB  - OBJECTIVE: The pattern of dopamine antagonism by metoclopramide suggests benefits
      in the treatment of tic disorders. The purpose of this study was to examine the
      efficacy and safety of metoclopramide in the treatment of children and
      adolescents with tic disorders. METHOD: Twenty-seven medication-free patients
      (age 11.9 +/- 2.7 years) with Tourette's disorder or a chronic tic disorder
      participated in an 8-week double-blind, randomized, placebo-controlled trial of
      metoclopramide. Metoclopramide was started at 5 mg daily and titrated as needed
      to a maximum dose of 40 mg daily. Tics were rated every 2 weeks, and adverse
      effects, including weight, cardiac, and laboratory measures, were monitored.
      RESULTS: After 8 weeks of treatment, subjects receiving metoclopramide showed a
      39% reduction in their total tic score on the Yale Global Tic Severity Scale,
      while subjects receiving placebo showed only a 13% reduction in tic severity (p =
      .001). Metoclopramide was well tolerated with no significant laboratory or
      cardiac changes noted other than an increase in serum prolactin. CONCLUSIONS: The
      results of this small controlled study suggest that metoclopramide is an
      effective and well-tolerated treatment for children and adolescents with tic
      disorders. Further trials are needed to confirm its efficacy and safety in
      pediatric patients and adults.

PMID- 15968233
TI  - A randomized, placebo-controlled study of once-daily atomoxetine in the school
      setting in children with ADHD.
AB  - OBJECTIVE: Five studies have demonstrated the effectiveness of atomoxetine
      compared with placebo in reducing symptoms of attention-deficit/hyperactivity
      disorder (ADHD) based on parent reports. The primary objective of this clinical
      trial was to assess the efficacy of once-daily atomoxetine compared with placebo
      using teacher reports. METHOD: One hundred fifty-three patients aged 8-12 years
      were randomly assigned to receive once-daily atomoxetine or placebo in a 2:1
      ratio for 7 weeks. ADHD symptoms at school were primarily assessed by baseline-to
      endpoint change on the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV
      Teacher Version: Investigator administered and scored (ADHDRS-IV-Teacher:Inv) as
      rated by investigators using teacher reports. RESULTS: ADHDRS-IV-Teacher:Inv
      total scores were significantly lower for children treated with atomoxetine
      compared with those treated with placebo (p = .001). Similar results were
      observed for the inattentive (p = .016) and hyperactive/impulsive (p < .001)
      ADHDRS-IV-Teacher:Inv subscales, the clinician-rated Clinical Global Impressions
      severity scale (p = .001), the Conners Global Index-Teacher scale (p = .008), and
      the Conners Parent Rating Scale-Revised: Short Form ADHD Index T-Score (p <
      .001). Discontinuations due to adverse events were low in both groups
      (atomoxetine 5.9%, placebo 0%, p = .096). CONCLUSIONS: This study extends
      previous results based on parent reports showing that once-daily administration
      of atomoxetine is safe and effective in improving ADHD symptoms in children and
      demonstrates that outcomes at school are similar when symptoms are reported by
      teachers.

PMID- 15968234
TI  - Developmental differences in the expression of childhood anxiety symptoms and
      fears.
AB  - OBJECTIVE: To examine age differences in the expression of childhood fears and
      anxiety symptoms. METHOD: A cross-sectional design was used to test recently
      formulated developmental hypotheses regarding the differential expression of
      childhood anxiety symptoms and fears in a community sample of youths (N = 145).
      Three groups of youths were compared: children aged 6-9 years (n = 47), preteens
      aged 10-13 years (n = 52), and adolescents aged 14-17 years (n = 46). Symptoms of
      separation anxiety, generalized anxiety, and social anxiety were assessed using a
      dimensional approach by both parent and child report. Fears were assessed by
      child report. RESULTS: The results indicated that there are systematic age
      differences in the expression of childhood fears and anxiety symptoms. Results
      also point toward specific symptoms predominant at certain ages (i.e., separation
      anxiety symptoms in youths aged 6-9 years, death and danger fears in youths aged
      10-13 years, and social anxiety symptoms as well as failure and criticism fears
      in youths aged 14-17 years) in partial support of predictions. CONCLUSIONS:
      Models of the etiology of childhood anxiety disorders tracing continuity and
      change over time should consider differences in the developmental expression of
      childhood fears and anxiety symptoms. Attention to developmental issues
      concerning symptom expression may be important in the clinical understanding of
      childhood anxiety.

PMID- 15968235
TI  - Face-emotion processing in offspring at risk for panic disorder.
AB  - OBJECTIVE: Panic disorder (PD) has been linked to perturbed processing of
      threats. This study tested the hypotheses that offspring of parents with PD and
      offspring with anxiety disorders display relatively greater sensitivity and
      attention allocation to fear provocation. METHOD: Offspring of adults with PD,
      major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer
      presented face photographs depicting angry, fearful, and happy faces. Offspring
      rated (1) subjectively experienced fear level, (2) how hostile the face appeared,
      and (3) nose width. Attention allocation was indexed by latency to perform
      ratings. RESULTS: Compared with offspring of parents without PD (n = 79),
      offspring of PD parents (n = 65) reported significantly more fear and had slower
      reaction times to rate fear, controlling for ongoing anxiety disorder in the
      offspring. Offspring with an anxiety disorder (n = 65) reported significantly
      more fear than offspring without an anxiety disorder but not when parental PD was
      controlled. Social phobia but no other anxiety disorder in offspring was
      associated with slower reaction times for fear ratings (but not greater fear
      ratings). Parental PD and offspring social phobia independently predicted slower
      reaction time. CONCLUSIONS: Results support an association between parental PD
      and offspring responses to fear provocation. Social phobia in children may have a
      specific relationship to allocation of attention to subjective anxiety during
      face viewing.

PMID- 15968236
TI  - A naturalistic study of referred children and adolescents with obsessive
      compulsive disorder.
AB  - OBJECTIVE: To report on clinical features, comorbidity, and response to
      pharmacotherapy in children and adolescents with obsessive-compulsive disorder
      (OCD) naturalistically followed and treated with serotonin reuptake inhibitors
      (SRIs). METHOD: A consecutive series of 94 patients (65 males, 29 females, age
      13.6 +/- 2.8 years), referred in the period January 2001-April 2004, diagnosed
      with a clinical interview (Diagnostic Interview for Children and Adolescents
      Revised), and followed for 10 +/- 6 months, were included in the study. RESULTS:
      Contamination obsessions and washing rituals were associated with less impairment
      than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as
      well as symmetry obsessions and ordering-repeating rituals were more frequently
      comorbid with tic disorders. According to the Clinical Global Impressions
      Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment.
      Nonresponders were more severely impaired and had a higher number of comorbid
      disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven
      patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed
      other medications. Patients receiving SRI monotherapy were less severely
      impaired; had a later onset of OCD; were at a younger age at the visit, had
      higher rates of depression and anxiety and lower rates of bipolar disorder,
      attention-deficit/hyperactivity disorder, and conduct disorder (p < .05).
      CONCLUSIONS: Long-term naturalistic prospective studies in pediatric patients
      with OCD might represent an important source of information for everyday care
      regarding the effectiveness of a treatment over extended periods of time under
      routine clinical conditions.

PMID- 15968237
TI  - Prospective study of posttraumatic stress disorder in parents of children with
      newly diagnosed type 1 diabetes.
AB  - OBJECTIVE: To determine the prevalence, course, and predictors of posttraumatic
      stress disorder (PTSD) in mothers and fathers of children with newly diagnosed
      type 1 diabetes. METHOD: Forty-nine mothers and 48 fathers of 52 children
      (response rate 65%) with newly diagnosed diabetes (age 6.5-15 years) were
      assessed at 6 weeks, 6 months, and 12 months after the diagnosis with the
      Posttraumatic Diagnostic Scale. RESULTS: The prevalence of current PTSD in
      mothers was 22.4% at 6 weeks, 16.3% at 6 months, and 20.4% at 12 months. In
      fathers, PTSD was found in 14.6%, 10.4%, and 8.3%, respectively. Mothers endorsed
      more symptoms of PTSD at all assessments. Multivariate analyses controlling for
      demographics, metabolic control, and threat appraisals revealed that in mothers,
      the number of preceding life events and PTSD symptoms at 6 months predicted PTSD
      at 12 months. In fathers, PTSD severity at 6 months was the only significant
      predictor for PTSD at 12 months. CONCLUSIONS: The results suggest that the
      diagnosis and treatment of diabetes in their child constitute traumatic events
      for parents. The findings confirm the applicability of a posttraumatic stress
      model for investigating the psychological impact of diabetes on parents.

PMID- 15968238
TI  - Family adversity in DSM-IV ADHD combined and inattentive subtypes and associated
      disruptive behavior problems.
AB  - OBJECTIVE: This study evaluated the relationship between a family adversity index
      and DSM-IV attention-deficit/hyperactivity disorder (ADHD) subtypes and
      associated behavior problems. The relationship of family adversity to symptoms
      and subtypes of ADHD was examined. METHOD: Parents and 206 children aged 7-13
      completed diagnostic interviews and rating scales about socioeconomic status,
      parental lifetime psychiatric disorders, marital conflict, and stressful life
      events. RESULTS: Children with ADHD combined type experienced more risk factors
      than community controls (p = .002) or children with ADHD predominantly
      inattentive type (p = .02). The families of children with ADHD combined type
      described more risk factors associated with family adversity than the families of
      children with ADHD inattentive type and the control group. Parent-rated symptoms
      of child inattention/disorganization were related uniquely to the adversity index
      score independently of conduct disorder symptoms. Children's perceptions of
      marital conflict were independently related to inattention and hyperactivity
      behaviors as rated by parents and teachers after control of all other risk
      factors. Oppositional defiant symptoms were independently related to marital
      conflict and maternal psychopathology, whereas conduct disorder symptoms were
      uniquely related to low socioeconomic status and maternal psychopathology.
      CONCLUSIONS: Family adversity is related to ADHD combined type in children and
      may be related specifically to ADHD symptoms in addition to conduct disorder
      symptoms.

PMID- 15968239
TI  - The Brief Impairment Scale (BIS): a multidimensional scale of functional
      impairment for children and adolescents.
AB  - OBJECTIVE: This article provides the results of the psychometric testing of the
      Brief Impairment Scale (BIS). The BIS is a 23-item instrument that evaluates
      three domains of functioning: interpersonal relations, school/work functioning,
      and self-care/self-fulfillment. It capitalizes on the strengths of existing
      global measures while addressing some of their limitations. METHOD: Cross
      sectional parent respondent data from one clinical (N = 757) and two community
      samples (N = 1,888 and 1,132) of children ranging in age from 4 to 17 years is
      employed to test the reliability and validity of the BIS. Receiver operating
      characteristic analyses are employed to assess useful cutoff scores on the scale.
      RESULTS: The total scale's internal consistency ranged from 0.81 to 0.88 and from
      0.56 to 0.81 on the three subscales. Test-retest reliability for individual items
      ranged from fair to substantial in all but six items. The BIS has high convergent
      and concurrent validity. Receiver operator characteristic analyses suggest
      possible thresholds for different uses. CONCLUSIONS: The BIS is psychometrically
      sound, useful in assessments and as an outcome measure in clinical practice and
      research. Its advantages over other global impairment instruments are that it is
      respondent based, short in administration time, and multidimensional.

PMID- 15968240
TI  - A CBT approach to inpatient psychiatric hospitalization.

PMID- 15968241
TI  - Evidence-based assessment of pediatric bipolar disorder, part I: base rate and
      family history.

PMID- 15968242
TI  - Current diagnosis and treatment of pancreatic cancer in China.
AB  - In China, morbidity and mortality for pancreatic cancer differs from that in most
      Western countries. Pancreatic cancer is the sixth leading cause of death from
      malignant disease in China, with an overall cumulative 5-year survival rate of 1%
      to 3%. Pancreatic cancer has the highest incidence in Shanghai (7.21/100,000) and
      the lowest (0.47/100,000) in the Hunan Province. As in the Western world, the
      main reason for the poor outcome of patients with pancreatic cancer is the late
      establishment of the diagnosis. Pancreatic cancer is seldom detected in early
      disease stages, and until now, the process of cancer initiation, progression, and
      formation of metastasis is not sufficiently understood. In this article, we
      reviewed recent data on patients in China with pancreatic cancer and obtained the
      most updated information on the different aspects of oncologic research,
      including epidemiology, molecular biology, diagnosis, and treatment.

PMID- 15968243
TI  - Monocyte anergy is present in patients with severe acute pancreatitis and is
      significantly alleviated by granulocyte-macrophage colony-stimulating factor and
      interferon-gamma in vitro.
AB  - OBJECTIVES: Severe acute pancreatitis (AP) is frequently associated with immune
      suppression, which increases the risk of infections, organ failure, and death.
      Our aims were to measure monocyte function (ie, HLA-DR expression and tumor
      necrosis factor-alpha [TNF-alpha] production as markers of immune suppression) in
      patients with severe AP and to determine whether treatment of blood samples with
      granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interferon-gamma
      (IFN-gamma) corrected the functional defects of monocytes in vitro. METHODS: The
      study consisted of 28 patients with severe AP who were treated at intensive care
      unit and in whom the proportion of HLA-DR-positive monocytes in the circulation
      was less than 70%, and 28 matched control subjects who were selected from healthy
      laboratory personnel. HLA-DR density was determined by whole blood flow
      cytometry. Monocyte TNF-alpha production in response to bacterial
      lipopolysaccharides (LPSs) was studied in a whole blood assay. Aliquots of blood
      were supplemented with IFN-gamma (all 28 patients), GM-CSF (the last 24
      patients), or both (the last 12 patients). RESULTS: The median proportion of HLA
      DR-positive monocytes was 45% in patients (range, 18%-73%) and was 98% in
      controls (range, 86%-100%; P < 0.001). TNF-alpha levels in response to LPSs were
      lower in patients (545 pg/mL; range, 84-1990 pg/mL) than in controls (1415 pg/mL;
      range, 660-5490 pg/mL; P < 0.001). The proportion of HLA-DR-positive cells
      correlated positively with TNF-alpha levels (r = 0.56; P < 0.01). Both GM-CSF and
      IFN-gamma increased HLA-DR expression of monocytes in patients (98%; range, 74%
      100% for GM-CSF; 99%; range, 86%-100% for IFN-gamma; both P < 0.001). The
      combination restored monocyte HLA-DR expression (99%; range, 96%-100%; P =
      0.002). Compared with basal levels, GM-CSF increased TNF-alpha production of
      monocytes both in blood samples from patients (median, 1320 pg/mL; range, 35-8015
      pg/mL) and controls (median, 3450 pg/mL; range, 1040-9835 pg/mL; both P < 0.001).
      IFN-gamma increased TNF-alpha production by monocytes in patients (683 pg/mL;
      range, 186-2705 pg/mL; P < 0.05) but not in controls (1658 pg/mL; range, 765-4755
      pg/mL; P = 0.31). With the combination of GM-CSF and IFN-gamma, the TNF-alpha
      levels of monocytes in patients (3185 pg/mL; range, 545-8280 pg/mL) and in
      controls (2800 pg/mL; range, 1080-6860 pg/mL) were comparable. CONCLUSIONS: The
      proportion of HLA-DR-positive monocytes correlates with TNF-alpha production, and
      they both reflect the degree of immune suppression. The low proportion of HLA-DR
      positive monocytes in AP can be reversed in vitro by GM-CSF and/or IFN-gamma. The
      GM-CSF and IFN-gamma treatments also increase LPS-induced TNF-alpha production.
      By the combination of GM-CSF and IFN-gamma, but not by either agent alone, LPS
      induced TNF-alpha production of monocytes was equally high in patients and in
      controls.

PMID- 15968244
TI  - Clinicopathological features of autoimmune pancreatitis in relation to elevation
      of serum IgG4.
AB  - OBJECTIVES: To examine the clinicopathological differences between patients with
      autoimmune pancreatitis in relation to presence or absence of elevated serum IgG4
      concentrations. METHODS: We divided 21 patients with autoimmune pancreatitis into
      2 groups on the basis of serum IgG4 concentration: elevated (>135 mg/dL) and low.
      The number of IgG4-immunoreactive plasma cells in the pancreas, bile duct,
      gallbladder, gastric mucosa, and abdominal lymph nodes was examined. RESULTS:
      Serum IgG4 concentrations were elevated in 14 patients (150-1890 mg/dL). No
      significant differences in age and sex, frequencies of pancreatic swelling,
      biliary stenosis, presence of autoantibodies, and salivary glands enlargement
      were identified between the 2 groups. Abdominal lymphadenopathy was detected at
      laparotomy more frequently in patients with high serum IgG4 (P < 0.05). Although
      no difference in number of IgG4-positive plasma cells infiltrating the pancreas
      was observed between the 2 groups, patients with elevated IgG4 tended to exhibit
      more of these cells infiltrating the wall of the bile duct and abdominal lymph
      nodes, significantly more of these cells infiltrating the gastric mucosa (P <
      0.01). CONCLUSION: IgG4-related phenomena occurred in various organs of patients
      with autoimmune pancreatitis associated with elevated IgG4, whereas these
      phenomena tended to be rather confined to the pancreas in patients with low serum
      IgG4.

PMID- 15968245
TI  - Regenerative and therapeutic effects of heparin-binding epidermal growth factor
      like growth factor on diabetes by gene transduction through retrograde pancreatic
      duct injection of adenovirus vector.
AB  - OBJECTIVES: In the adult pancreas, pre-existing beta cells, stem cells, and
      endocrine progenitor cells residing in the duct lining are considered important
      sources for beta-cell regeneration. A member of the epidermal growth factor (EGF)
      family, heparin binding (HB)-EGF, may promote this process. We examined whether
      HB-EGF gene transduction into duct cells could promote beta-cell regeneration.
      METHODS: We administered an HB-EGF adenovirus vector construct to male Institute
      of Cancer Research mice by retrograde injection through the pancreatic duct. We
      also performed HB-EGF gene transduction into cultured duct cells. RESULTS: On
      immunohistochemical and histomorphometric analysis of the experimental group,
      insulin-positive cells differentiated from duct cells, and the 5-bromo-2
      deoxyuridine labeling index of beta cells was significantly increased. beta-cell
      mass was also increased, and the glucose tolerance of diabetic mice was improved
      at 12 weeks after injection. Using cultured pancreatic duct cells, we confirmed
      that HB-EGF gene transduction induced both insulin gene expression and insulin
      production by these cells. CONCLUSIONS: These results indicate that HB-EGF gene
      transduction into adult pancreatic duct cells not only promotes the proliferation
      of pre-existing beta cells but also leads to beta-cell differentiation from duct
      cells, and the resulting increase in beta-cell mass improves glucose tolerance.

PMID- 15968246
TI  - Does resveratrol prevent free radical-induced acute pancreatitis?
AB  - OBJECTIVE: The purpose of this study was to examine protective and antioxidative
      effect of stilbene derivatives, resveratrol and diethylstilbestrol, in
      experimental acute pancreatitis (EAP). METHODS: EAP was induced in male Wistar
      rats by retrograde injection of tert-butyl hydroperoxide (ButOOH) solution, a
      well-known prooxidant agent, into the common bile pancreatic duct. After a 3-hour
      observation, the animals were killed. Blood samples were collected. Each pancreas
      was removed and weighed. Tissue samples were taken for microscopic studies. The
      carbonyl and sulfhydryl (SH) group levels were estimated in the homogenate.
      RESULTS: Examination using light microscopy revealed morphologic changes in
      pancreata removed from EAP rats, namely focal edema, acinar cell vacuolization,
      and focal necrosis of pancreatic acini. The electron microscopic analysis also
      showed changes in their subcellular structures: dilated cisternae of the rough
      endoplasmic reticulum, swollen mitochondria, and "debris" of mitochondrial
      cristae. These changes corresponded with higher activities of serum amylase and
      tissue carbonyl groups levels and decreased SH group level compared with
      controls. Changes in pancreata were much less pronounced in the rats that
      received resveratrol or diethylstilbestrol for 8 days prior to ButOOH injection.
      CONCLUSION: Stilbene derivatives prevent pancreatic cells from structural changes
      during ButOOH-induced acute pancreatitis.

PMID- 15968247
TI  - Natural disruption of group 2 phospholipase A2 gene protects against choline
      deficient ethionine-supplemented diet-induced acute pancreatitis and lung injury.
AB  - OBJECTIVES: Group 2 phospholipase A2 (PLA2) plays an important role in the
      pathogenesis of multiple organ failure associated with acute pancreatitis. C57
      BL/6J mice are natural group 2 PLA2 knockout mice lacking group 2 PLA2 mRNA. To
      clarify the role of group 2 PLA2 in the exacerbation of acute pancreatitis, we
      studied the biologic and histologic alterations in choline-deficient and
      ethionine-supplemented (CDE) diet-induced pancreatitis in group 2 PLA2-deficient
      C57 BL/6J mice and compared them with those in wild-type mice. METHODS: Female
      C57 BL/6J mice weighing 20 to 22 g were fed a CDE diet for 3 days to induce
      pancreatitis. Female C3H/HEJ mice were used as controls. Mice were killed on days
      1, 2, and 3 after the onset of the CDE diet. The severity of pancreatitis was
      evaluated by survival rate, plasma PLA2 activity, serum amylase level, histologic
      changes in the pancreas and lung, and myeloperoxidase activity in the lung.
      RESULTS: The survival rate of C57 BL/6J mice was 100% up to day 3 after the onset
      of the CDE diet, whereas that of the control mice was 42% on day 3. Plasma PLA2
      activity in control mice increased on day 3 but did not increase in C57 BL/6J
      mice. Serum amylase activity on day 3 in C57 BL/6J mice was 15,480 +/- 3036
      SU/dL, which was significantly lower than that in the control mice (43,760 +/-
      8657 SU/dL, P < 0.01). Histologic changes in the pancreas of C57 BL/6J mice were
      markedly milder than in control mice. The degree of alveolar membrane thickening
      and infiltration of inflammatory cells in the lung of C57 BL/6J mice were overtly
      less than those of the controls. Myeloperoxidase activity in the lung of C57
      BL/6J mice was lower, albeit insignificant, than in C3H/HEJ mice. CONCLUSIONS:
      Natural disruption of the group 2 PLA2 gene protects against CDE diet-induced
      acute pancreatitis and associated lung injury. These findings support the view
      that group 2 PLA2 is one of the factors in the exacerbation of severe acute
      pancreatitis.

PMID- 15968248
TI  - Proinflammatory role of trypsin and protease-activated receptor-2 in a rat model
      of acute pancreatitis.
AB  - OBJECTIVES: The pathophysiology of acute pancreatitis is strongly associated with
      autoactivation of trypsin. The biologic activity of trypsin on cells is
      attributed to the activation of protease-activated receptor-2 (PAR-2). We
      hypothesize that trypsin may activate acinar cells or inflammatory cells through
      PAR-2 signals in acute pancreatitis. METHODS: We immunochemically analyzed the
      expression of PAR-2 in the rat acinar cell line, ARIP, and the rat pancreas,
      using anti-rat PAR-2 cleavage site (PCS) and anti-rat PAR-2 N-terminal fragment
      (PNF) antibodies. Plasma levels of PNF were determined. Furthermore, the effects
      of the anti-rat PCS antibody and nafamostat mesylate, a potent trypsin inhibitor,
      on PAR-2 activation during acute pancreatitis were also analyzed. RESULTS: ARIP
      cells expressed PAR-2, which was activated by exogenous trypsin activity. We also
      showed that PAR-2 is strongly expressed in pancreatic acinar and duct cells and
      that it is activated in rat cerulein-induced acute pancreatitis. The anti-rat PCS
      antibody and nafamostat mesylate reduced interleukin-6 and interferon gamma
      production and alleviated distant organ injury. CONCLUSIONS: These results
      suggest that trypsin and its specific receptor, PAR-2, play an important role in
      cytokine production and the resultant development of distant organ injury during
      rat acute pancreatitis.

PMID- 15968249
TI  - Comparative analysis of direct pancreatic function testing versus morphological
      assessment by endoscopic ultrasonography for the evaluation of chronic
      unexplained abdominal pain of presumed pancreatic origin.
AB  - OBJECTIVES: The diagnosis of "minimal change" chronic pancreatitis (MCCP) is
      often considered when conventional imaging studies are unrevealing in a patient
      population with abdominal pain of presumed pancreatic origin. Direct pancreatic
      function testing using secretin as a secretagogue (ST) has been considered the
      most sensitive method to diagnose MCCP but is not widely available to clinicians.
      Endoscopic ultrasound (EUS) allows detailed imaging of pancreatic architecture,
      but the sensitivity and specificity for MCCP remain to be determined. We sought
      to compare the accuracy of EUS and ST in patients with presumed MCCP. METHODS:
      Seventy-four patients referred to our pancreas clinic with unexplained abdominal
      pain and previously negative imaging studies underwent an ST for evaluation of
      possible MCCP. Twenty-one of these also underwent EUS. EUS images were read by 1
      of 2 experts blinded to ST results. RESULTS: Using ST as the "gold standard," EUS
      had a maximum sensitivity of 71% when the cut-off for diagnosis was set at at
      least 3 EUS features. Conversely, maximum specificity (92%) was seen when the cut
      off value was set at at least 6 EUS criteria. Diagnostic certainty was only 50%
      (positive predictive value = 0.5) when at least 6 criteria were used as the cut
      off. MCCP was excluded with greater than 70% certainty when less than 3 criteria
      were present. At the best cut-off value of at least 4 features, EUS had a
      sensitivity of 57% and a specificity of 64%. CONCLUSIONS: In this patient
      population with abdominal pain of presumed pancreatic origin, EUS and standard
      pancreatic function testing are often discordant. If ST is assumed to be the
      reference against which other tests are compared, EUS is less accurate than ST in
      diagnosing MCCP.

PMID- 15968250
TI  - Factors predicting recurrence after resection of pancreatic ductal carcinoma.
AB  - OBJECTIVE: Pancreatic ductal carcinoma frequently recurs postoperatively, and we
      analyzed clinicopathological features of patients treated by surgical resection
      to find predictors of postoperative recurrence. METHODS: A retrospective cohort
      study was performed that included 69 patients between 1985 and 2003.
      Clinicopathologic factors were evaluated for tumor recurrences by univariate and
      multivariate analyses. RESULTS: Mean survival time and actuarial 5-year disease
      specific survival were significantly lower in cases of hepatic metastasis (13
      months, 0%) and in cases of peritoneal carcinomatosis (15 months, 6.8%) than in
      cases of local retroperitoneal recurrence (30 months, 21%). Univariate and
      logistic regression analyses showed undifferentiated adenocarcinoma to be
      independently associated with hepatic metastasis (odds ratio, 7.4; 95% confidence
      interval, 1.5-37.0) and invasion of the portal vein to be independently
      associated with peritoneal carcinomatosis (odds ratio, 4.0; 95% confidence
      interval, 1.2-12.8). Multivariate analysis showed undifferentiated
      adenocarcinoma, invasion of the anterior capsule, and invasion of the portal vein
      to be independent prognostic factors. CONCLUSION: Undifferentiated adenocarcinoma
      and invasion of the portal vein are predictors of poor outcome and are related to
      hepatic metastasis and peritoneal carcinomatosis, respectively. Postoperative
      adjuvant chemotherapy, including intra-arterial chemotherapy, should be selected
      according to prediction of the patterns of recurrence.

PMID- 15968251
TI  - Usefulness of plasma vascular endothelial growth factor in the diagnosis of
      pancreatic carcinoma: differential diagnosis, tumor progression, and patient
      survival.
AB  - OBJECTIVES: This study aimed to examine the usefulness of plasma vascular
      endothelial growth factor (p-VEGF) in patients with pancreatic carcinoma (PC) as
      a tumor marker for PC in comparison with chronic pancreatitis (CP) and to clarify
      the relationship between p-VEGF and the clinicopathological features of PC.
      METHODS: The subjects were 69 patients with PC, 35 with CP, and 26 healthy
      volunteers (control group). The p-VEGF levels were measured by enzyme-linked
      immunoassay. RESULTS: p-VEGF levels were significantly higher in the PC group
      compared with the CP and control groups (P < 0.0001). A cut-off level of 149.5
      pg/mL, discriminating between PC and CP, was determined based on a receiver
      operating characteristic curve. Using this cut-off level, the sensitivity was
      60%, specificity was 96%, and accuracy was 73%. Patients with PC with distant
      metastases exhibited a significantly higher level of p-VEGF compared with those
      without metastasis (P = 0.0113). Multivariate analysis indicated that a high
      level of p-VEGF was an independent prognostic factor, and a significant
      association was observed between p-VEGF and median survival time (P = 0.0092).
      CONCLUSIONS: p-VEGF proved useful in differentiating between PC and CP, and in
      patients with PC, a high level of p-VEGF may be a predictor of distant metastases
      and poor prognosis.

PMID- 15968252
TI  - Endocrine tumor and intraductal papillary mucinous neoplasm of the pancreas: a
      fortuitous association?
AB  - OBJECTIVES: Pancreatic endocrine tumors (PETs) and intraductal papillary mucinous
      neoplasms (IPMNs) of the pancreas are rare diseases of the pancreas. Cases of
      association of endocrine and exocrine neoplasms of the pancreas have been
      reported, corresponding to mixed or amphicrine tumors. The aim of this report is
      to describe a series of 6 patients with an original association of IPMN and PET
      of the pancreas. METHODS: Among 108 and 103 patients operated on in our center
      between January 1997 and December 2003 for PETs and IPMNs, respectively, we
      identified 6 patients with both PET and IPMN, diagnosed on pathologic examination
      with an immunohistochemical study. RESULTS: Preoperative diagnosis was
      unspecified pancreatic tumor (n = 1), IPMN (n = 2), and association of PET and
      IPMN (n = 3). IPMN involved the main pancreatic duct in 4 patients and was
      classified as benign (n = 4), borderline (n = 1), or malignant noninvasive (n =
      1). PETs measured 1.1 to 3 cm and were malignant in 1 patient (lymph node
      invasion). When analyzed by immunohistochemistry, 2 cases expressed glucagon, 1
      expressed somatostatin, and 1 expressed insulin. CONCLUSION: This study describes
      a new aspect of endocrine-exocrine pancreatic neoplasm association. The frequency
      of the association of PET and IPMN is too large to be fortuitous. Further studies
      are needed to understand its mechanism.

PMID- 15968254
TI  - Peripyloric lymph node metastasis is a rare condition in carcinoma of the
      pancreatic head.
AB  - OBJECTIVES: Pylorus preserving pancreatoduodenectomy (PPPD) was introduced to
      achieve a better functional result compared with the conventional Kausch-Whipple
      procedure (PD). In PPPD, peripyloric and perigastric lymphatic tissue is not
      removed compared with PD. The aim of this prospective study was to identify the
      frequency of peripyloric and perigastric lymph node metastases in ductal
      adenocarcinoma of the pancreatic head (PC). METHODS: Fifty specimens following
      Kausch-Whipple procedure including partial gastric resection for PC were analyzed
      for peripyloric and perigastric lymph node metastases by a standardized clearing
      technique. All lymph nodes of the specimens were counted, discriminating between
      those not removed ("group A") and those removed ("group B") in pylorus preserving
      resection of the pancreatic head. Additionally, the duodenal wall and
      paraduodenal tissue at a potential duodenal resection margin 2 cm distal of the
      pylorus were investigated histologically. RESULTS: Three of the 50 specimens (6%)
      carried peripyloric lymph node metastases, whereas 32 of the 50 specimens (64%)
      contained lymph node metastases in total. Four of 362 group A and 90 of 748 group
      B lymph nodes showed metastatic spread of the carcinoma. The 4 lymph node
      metastases in group A could be identified exclusively in 88 peripyloric lymph
      nodes but in none of the 274 perigastric lymph nodes at the lesser or greater
      curvature. In 2 of the 3 patients with peripyloric lymph node metastases, these
      lymph nodes were the only lymph nodes with metastatic involvement in the entire
      specimen. In 1 specimen, a small tumor nest of less than 2 mm in diameter was
      detected at a distance of less than 1 mm to the pylorus, although pyloric
      involvement was not suspected intraoperatively. The potential PPPD resection
      margin of the duodenal wall was not infiltrated by intramural tumor spread in any
      specimen. CONCLUSION: In a minority of 6%, PC metastasizes in peripyloric lymph
      nodes. Lymph nodes of the lesser and greater curvature of the stomach are not
      involved in patients with PC. Thus, we conclude by the data of this prospective
      study that the limited benefits of the extended lymph node dissection in a
      conventional Kausch-Whipple resection are far outweighed by the disadvantages
      construed by this procedure.

PMID- 15968253
TI  - Serum paraoxonase (a high-density lipoprotein-associated lipophilic antioxidant)
      activity and lipid profile in experimental acute pancreatitis.
AB  - OBJECTIVE: This study was designed to determine the serum lipid profile and the
      activity of paraoxonase (PON1, the lipophilic antioxidant component of high
      density lipoprotein [HDL]-cholesterol) in acute pancreatitis. METHODS: Acute
      pancreatitis was induced by injection of ethyl alcohol into the common biliary
      duct. Oxidative stress marker (malonyldialdehyde), lipid profile, and PON1
      activity were determined in the serum. RESULTS: In the acute pancreatitis group,
      whereas the mean levels of total cholesterol, low-density lipoproteins, and
      malonyldialdehyde were significantly higher (P < 0.001 for each), HDL level and
      PON1 activity were found to be significantly lower (P < 0.001 for each).
      CONCLUSIONS: Our results suggest that an abnormal lipid profile and decreased
      PON1 activity may have a role in the pathogenesis of acute pancreatitis in which
      HDL-associated antioxidant defense is impaired.

PMID- 15968255
TI  - Efficacy of endoscopic nasobiliary drainage for the prevention of pancreatitis
      after papillary balloon dilatation: a pilot study.
AB  - OBJECTIVE: Endoscopic papillary balloon dilatation (EPBD) has been reported to
      increase the risk of post-endoscopic retrograde cholangiopancreatography (ERCP)
      pancreatitis (4%-11%). Based on the hypothesis that performing endoscopic
      nasobiliary drainage (ENBD) could prevent this complication, we performed EPBD
      combined with ENBD (EPBD/ENBD) and analyzed the risk of pancreatitis. METHODS:
      Thirty-four patients underwent EPBD followed by ENBD for common bile duct
      stone(s). Serum amylase levels the following morning and incidence of
      pancreatitis were compared with those previously reported and with complications
      of simple diagnostic ERCP performed in our institution. RESULTS: After EPBD/ENBD,
      amylase levels the following morning were 214.5 +/- 152.9 U/L, and no cases
      developed pancreatitis or hyperamylasemia (>3 times normal). These outcomes were
      favorable compared with previous EPBD reports. Furthermore, despite the stress of
      EPBD/ENBD after ERCP, these outcomes were better, even compared with simple ERCP
      performed at our institution [amylase levels: 318.7 +/- 475.2 U/L;
      hyperamylasemia: 16.5% (P = 0.006); pancreatitis: 7.1%]. CONCLUSION: Although
      EPBD has been regarded as a risk factor for post-ERCP pancreatitis, our results
      suggest the possibility that application of ENBD after EPBD decreases the
      incidence of pancreatitis and should be studied further. We speculate that ENBD
      itself prevents pancreatic duct obstruction by residual stones or papillary
      edema.

PMID- 15968256
TI  - Mixed serous cystadenoma with mucinous cystadenoma of the pancreas.
AB  - We report a case of serous cystadenoma of the pancreas mixed with mucinous
      cystadenoma. A 65-year-old woman was admitted to our hospital for evaluation of a
      palpable, elastic, hard mass measuring 6 cm in diameter in the right upper
      quadrant of the abdomen. A diagnosis of mucinous cystadenocarcinoma of the
      pancreas was made, and pancreatoduodenectomy was performed. The tumor was
      composed of a dominant compartment of macroscopic cyst, and its thick wall was
      filled with numerous microscopic cysts. The light microscopy findings with
      hematoxylin and eosin staining, and by the periodic acid-Schiff reaction, were
      almost perfectly consistent with the characteristics of microcystic or glycogen
      rich cystadenoma, but the apical portion of the cytoplasm of the neoplastic cells
      was stained with Alcian blue at pH 2.4 and by the mucicarmine method. Neoplastic
      cells containing epithelial acidic mucin are usually found in mucinous
      cystadenomas. No K-ras point mutations were detected at the sites where
      neoplastic cells were present, whether or not they contained epithelial acidic
      mucin. Pancreatic serous cystadenomas that include a mucinous-cystadenoma
      component are extremely rare, and the difference between serous and mucinous
      cystadenomas is not always distinct.

PMID- 15968257
TI  - Is there a role for chemoradiation in the management of cystadenocarcinoma of the
      pancreas?
AB  - Despite a paucity of data, cystadenocarcinoma of the pancreas has been considered
      to be resistant to chemoradiation, with a limited effect similar to that of the
      more common pancreatic adenocarcinoma. We describe a case of a partially excised
      cystadenocarcinoma with a positive surgical margin that was treated by
      neoadjuvant chemoradiation. No epithelial elements were found on histologic
      examination after reresection. Three previous cases of dramatic response of
      pancreatic cystadenocarcinoma to chemoradiation have been described in the
      literature. The current dogma alleging poor response of pancreatic
      cystadenocarcinoma to chemoradiation may be in error.

PMID- 15968258
TI  - Hot topics: what to expect during a JACHO survey.

PMID- 15968260
TI  - Mechanisms of action of topical therapies and the rationale for combination
      therapy.
AB  - The advent of new topical agents such as topical calcineurin inhibitors, as well
      as the reformulations of older agents in new vehicles, has broadened the
      treatment approaches to psoriasis and atopic dermatitis. The clinician must now
      consider additional novel physiologic pathways and mechanisms of action as well
      as expanding options for combination therapy. Combination therapy is especially
      beneficial when the selected agents possess differing mechanisms of action that
      provide additive or synergistic efficacy, reducing the required doses of the
      individual agents compared with monotherapy and potentially limiting side
      effects. Therapeutic approaches also can be rotated or used in various sequences
      for maintenance therapy. In psoriasis, a number of trials have demonstrated the
      effectiveness of combination therapy. Although combination therapy has not been
      extensively studied in atopic dermatitis, many practitioners combine topical
      corticosteroids and topical calcineurin inhibitors in their clinical practice
      because the two drug classes have different and possibly complementary mechanisms
      of action. For both diseases, the decision as to what agents are combined must
      also be tempered by patient type, disease presentation or severity, and patient
      preferences.

PMID- 15968262
TI  - Therapeutic options in the treatment of psoriasis and atopic dermatitis.
AB  - A variety of therapeutic options are available to treat psoriasis and atopic
      dermatitis (AD). Local agents typically are used to treat localized and milder
      forms of disease, whereas phototherapy and systemic agents are used for more
      generalized and severe disease. Various combinations and sequences of topical or
      systemic therapies, or both, have been utilized in the treatment of psoriasis
      and, less frequently, of AD. Conventional systemic therapies for psoriasis, such
      as corticosteroids, oral calcineurin inhibitors, antimetabolites, and retinoids,
      are limited by their propensity to cause serious side effects. More recently, a
      number of immunobiologic agents, such as monoclonal antibodies, recombinant
      cytokines, and fusion proteins, have been approved by the Food and Drug
      Administration or are undergoing development as systemic antipsoriatic
      treatments. In many of these categories, a number of exciting new therapies are
      in development that may augment the existing armamentarium available to
      clinicians for the treatment of inflammatory skin diseases.

PMID- 15968261
TI  - A novel foam vehicle for delivery of topical corticosteroids.
AB  - Skin, particularly the uppermost layer--the stratum corneum--presents a
      formidable, largely impassable barrier to the entry of most compounds. Recently,
      a novel thermolabile, low-residue foam vehicle, VersaFoam (Connetics Corp, Palo
      Alto, Calif), has emerged that offers a number of clinical and cosmetic
      advantages for the delivery of therapeutic agents through the skin. Two
      corticosteroids--mid-potency betamethasone valerate and ultra-high-potency
      clobetasol propionate--are now available in this formulation, and other products
      are in development to deliver clindamycin and ketoconazole in the foam vehicle. A
      series of in vitro studies have demonstrated that the new foam has the ability to
      deliver the active drug at an increased rate compared with other vehicles. These
      findings suggest that the new foam utilizes a nontraditional "rapid-permeation"
      pathway for the delivery of drugs. It is likely that components within the foam
      (probably the alcohols) act as penetration enhancers, and reversibly alter the
      barrier properties of the outer stratum corneum, thus driving the delivered drug
      across the skin membrane via the intracellular route. This is in contrast to
      traditional topical delivery vehicles, which must first rely on hydration of the
      intercellular spaces in the stratum corneum to achieve drug delivery. The latter
      mechanism reflects a hydration-dependent process, which may result in
      comparatively slower drug permeation.

PMID- 15968263
TI  - Clinical studies of a new vehicle formulation for topical corticosteroids in the
      treatment of psoriasis.
AB  - Topical corticosteroids have been the mainstay of topical anti-inflammatory
      therapy of psoriasis and are available in different treatment strengths or doses
      and various formulations or vehicles. Traditional formulations have included
      ointments, creams, and lotions. More recently, the mid-potency corticosteroid
      betamethasone valerate (BMV) and the ultra-high-potency corticosteroid clobetasol
      propionate (CP) have become available in a novel, thermolabile, low-residue foam
      vehicle for topical application. This review examines recent clinical studies on
      efficacy and safety of these two new formulations, BMV 0.12% foam (Luxiq;
      Connetics Corp, Palo Alto, Calif) and CP 0.05% foam (OLUX, Connetics Corp), as
      treatments for scalp and nonscalp psoriasis. The studies demonstrated that BMV
      foam and CP foam are safe and effective treatments for psoriasis affecting scalp
      and nonscalp regions of the body. BMV foam and CP foam were absorbed more rapidly
      and demonstrated greater total absorption than their respective comparison
      formulations, namely BMV lotion and CP solution. The foam vehicle also appears to
      be associated with better compliance and improvements in quality of life. The
      unique nature of the foam vehicle, together with the positive findings of in
      vitro studies suggest these new foam formulations may expand the options
      currently available for combination therapy.

PMID- 15968264
TI  - Corticosteroids: options in the era of steroid-sparing therapy.
AB  - Topical corticosteroids remain the most commonly used topical treatments for
      inflammatory dermatoses, including psoriasis and atopic dermatitis. Topical
      corticosteroids are available in a variety of vehicles-creams, ointments,
      lotions, gels, and, more recently, foam. The vehicle used can substantially
      affect the individual agent's clinical action, potency, and acceptability to the
      patient. Moreover, some vehicles are better suited for specific body areas.
      Selection of the appropriate product should be determined by area of usage,
      physician experience, cost, and patient preference, particularly regarding
      vehicle. Although topical corticosteroids are associated with several side
      effects, including skin atrophy, telangiectases, purpura, and striae formation,
      appropriate usage can minimize these occurrences. Judicious use includes short
      term, appropriate application as initial monotherapy or in combination strategies
      with other therapeutic agents that ideally possess complementing mechanisms of
      action. Examples include pulsing with high-potency topical corticosteroids and
      combination regimens with other topical agents such as topical calcineurin
      inhibitors, calcipotriene, or tazarotene. Appropriate education of patients and
      caregivers alike will facilitate the optimal use of these medications.

PMID- 15968265
TI  - A clinician's paradigm in the treatment of psoriasis.
AB  - Psoriasis is a chronically recurring inflammatory disease that affects the skin,
      scalp, and joints. It ranges in severity from mild to severe, and patients with
      moderate to severe disease experience significant deterioration in quality of
      life. The goals of psoriasis treatment are to gain initial and rapid control of
      the disease process, decrease the percentage of body surface area involved,
      decrease plaque lesions, achieve and maintain long-term remission, minimize
      adverse events, and improve patient quality of life. Therapy varies depending on
      disease severity and spread and will shift from control of acute flares to long
      term maintenance. Topical treatment for mild psoriasis includes the use of
      topical corticosteroids, calcipotriene, tazarotene, topical tars, anthralin, and
      keratolytics. Treatment of moderate to severe psoriasis includes systemic
      therapies, such as methotrexate, acitretin, cyclosporine, and biologic agents.
      Treatment can be effected using combination, rotational, or sequential regimens.
      Treatment algorithms developed by a 2002 consensus conference are described.
      Because some degree of therapy will always be necessary, ranging from maintenance
      of long-term remission to control of acute psoriasis flares, each patient
      requires an individualized plan.

PMID- 15968266
TI  - A clinician's paradigm in the treatment of atopic dermatitis.
AB  - Successful management of atopic dermatitis requires a multipronged approach that
      includes skin barrier function care, use of topical or systemic agents, and
      identification and elimination of precipitating or exacerbating factors. Because
      the origin of atopic dermatitis is multifactorial and trigger factors differ
      among patients, treatment plans must be specific to the individual patient. This
      article offers an example of a permutational, or flexible, treatment paradigm.
      The approach utilizes 4 topical regimens--high-potency topical corticosteroids,
      lowest effective potency topical corticosteroids, topical calcineurin inhibitors
      (TCIs), or topical corticosteroid/TCI combinations--as initial therapy in a
      variety of induction protocols, as determined by the severity of a patient's
      condition and history. The paradigm permits treatment to progress from a chosen
      induction therapy to maintenance therapy. During the patient's induction therapy,
      as soon as an acceptable level of clearance is achieved, therapy should be
      adjusted to a maintenance regimen, such as monotherapy with either a TCI or a
      lowest effective potency topical corticosteroid (the latter used intermittently)
      or an alternation of the two agents. If there is no clearance or positive
      response with the initial induction protocol, the clinician should move to one of
      the alternative regimens.

PMID- 15968267
TI  - Involving the patient: impact of inflammatory skin disease and patient-focused
      care.
AB  - Atopic dermatitis (AD) and psoriasis are common chronic inflammatory diseases
      that are associated with significant psychosocial morbidity and a decrease in
      health-related quality of life (QOL). To better understand the effects of these
      two diseases on quality of life, as reported in the literature, a review of all
      English-language articles from 1970 to 2003 was performed using PubMed. Results
      from these studies and surveys illustrate the profound negative impact exerted by
      these conditions and the importance of early and appropriate treatment. These
      concerns can be incorporated into patient management strategies that focus on a
      new model for healthcare delivery, "patient-centered care," in which QOL plays an
      integral role. The impact of AD and psoriasis on physical, social, psychological,
      and financial aspects of life should not be trivialized and must be considered
      with the same importance as other chronic conditions. Because psoriasis and AD
      are chronic conditions that require patient and/or caregiver involvement for
      optimal management, the concept of patient-centered care with its emphasis on
      effective two-way communication is particularly important and useful for the
      clinician.

PMID- 15968268
TI  - Atopic dermatitis.
AB  - Atopic dermatitis (AD) is commonly associated with immunoglobulin E (IgE)
      antibody-related mechanisms, which are the focus of this article. The vast
      majority of patients with AD exhibit hyperproduction of IgE, particularly during
      disease onset or flare. IgE-dependent late-phase reactions may influence the
      chronic inflammatory response in AD. Clearly, genetics plays a major role in
      determining who develops AD. However, the recent increase in AD prevalence
      suggests that a complex interaction between environmental factors and
      susceptibility genes results in clinical expression of the disorder. These
      immunologic "triggers" differ among individuals and include various foods,
      airborne allergens, irritants and contactants, hormones, stress, climate, and
      microorganisms. Although much about AD remains to be elucidated, our current
      understanding of its pathophysiology has provided clinicians with the ability to
      construct more rational therapeutic interventions, including multiple-agent
      regimens that provide both immediate relief and effective long-term management.
      Future advances will come from identification of the genes causing this disease
      and further elucidation of the immunoregulatory mechanisms involved in the
      pathogenesis of AD.

PMID- 15968269
TI  - Psoriasis--recent advances in understanding its pathogenesis and treatment.
AB  - Although not completely understood, there is clearly a genetic component in the
      development of psoriasis. Twin studies show a 67% concordance for monozygotic
      twins versus 18% for dizygotic twins. This lack of complete concordance in
      monozygotic twins suggests multifactorial inheritance and interaction between
      genetic predisposition and the environment. At present, 8 different psoriasis
      susceptibility loci have been identified in genome-wide linkage scans, including
      locations on 15 different chromosomes. Genetic connections have been made between
      psoriasis and other diseases, including atopic dermatitis, rheumatoid arthritis,
      and Crohn's disease. A variety of approaches are available for the treatment of
      psoriasis, ranging from topical agents for milder forms of the disease to
      phototherapy and systemic agents for severe psoriasis. Despite the importance of
      systemic therapies and recent advances represented by biologic agents, topical
      treatments will probably remain the mainstay of psoriasis therapy for most
      patients. The advent of new, cosmetically attractive vehicles may enhance
      compliance, add to the use of topical agents, and potentially improve patient
      outcomes.

PMID- 15968270
TI  - DNA processing is not required for ATM-mediated telomere damage response after
      TRF2 deletion.
AB  - Telomere attrition and other forms of telomere damage can activate the ATM kinase
      pathway. What generates the DNA damage signal at mammalian chromosome ends or at
      other double-strand breaks is not known. Telomere dysfunction is often
      accompanied by disappearance of the 3' telomeric overhang, raising the
      possibility that DNA degradation could generate the structure that signals. Here
      we address these issues by studying telomere structure after conditional deletion
      of mouse TRF2, the protective factor at telomeres. Upon removal of TRF2 from
      TRF2(F/-) p53-/- mouse embryo fibroblasts, a telomere damage response is observed
      at most chromosome ends. As expected, the telomeres lose the 3' overhang and are
      processed by the non-homologous end-joining pathway. Non-homologous end joining
      of telomeres was abrogated in DNA ligase IV-deficient (Lig4-/-) cells.
      Unexpectedly, the telomeres of TRF2-/- Lig4-/- p53-/- cells persisted in a free
      state without undergoing detectable DNA degradation. Notably, the telomeres
      retained their 3' overhangs, but they were recognized as sites of DNA damage,
      accumulating the DNA damage response factors 53BP1 and gamma-H2AX, and activating
      the ATM kinase. Thus, activation of the ATM kinase pathway at chromosome ends
      does not require overhang degradation or other overt DNA processing.

PMID- 15968271
TI  - Mutational activation of BRAF is not a major event in sporadic childhood
      papillary thyroid carcinoma.
AB  - Papillary thyroid carcinoma may encompass a mixed group of neoplasms where
      divergence in clinical behavior may reflect distinct genetic alterations. For
      example, young patients with papillary thyroid carcinoma have a better prognosis
      than affected adults, and their carcinomas are much more likely to harbor
      chromosomal rearrangements involving the RET proto-oncogene. Mutational
      activation of the BRAF oncogene has recently been identified as the most common
      genetic alteration in papillary thyroid carcinoma, but little is known about its
      frequency as a function of patient age. We tested 20 papillary thyroid carcinomas
      from young patients ranging from 10 to 17 years of age for the thymine (T) -->
      adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using a newly
      developed assay that employs a novel primer extension method (Mutector assay).
      The prevalence of BRAF mutation was compared with a larger group of papillary
      thyroid carcinomas from previously tested adult patients (>20 years). BRAF
      mutations were not common in papillary thyroid carcinomas from young patients
      compared to their counterparts in adults (20 vs 77%; OR=13.3, 95% confidence
      interval (CI)=3.4-56.5; P<0.0001), but they become increasingly prevalent with
      advancing patient age (OR as a function of age at 10-year intervals=1.80 CI=1.33
      2.44; P<0.001). Unlike papillary thyroid carcinomas that arise in adults,
      mutational activation of BRAF is not a major genetic alteration in papillary
      thyroid carcinomas that arise in young patients. The increasing frequency of BRAF
      mutations as a function of age could help account for the well documented but
      poorly understood observation that age is a relevant prognostic indicator for
      patients with papillary thyroid carcinoma.

PMID- 15968272
TI  - Response to Pantanowitz et al. Regarding our paper on the utility of the
      detection of HHV-8 LNA-1 by immunohistochemistry in the diagnosis of Kaposi's
      sarcoma.

PMID- 15968275
TI  - T-cell lymphoproliferative disorder following a full haplotype-mismatched
      haematopoietic stem cell transplant in a patient with acute myeloid leukaemia.

PMID- 15968276
TI  - Transplantation of CD34+ selected peripheral blood to HLA-identical sibling
      patients with aplastic anaemia: results from a single institution.
AB  - We evaluated the use of CD34+ selected allogeneic peripheral blood as a source of
      hematopoietic progenitors for allogeneic transplantation in 11 patients with
      aplastic anemia (AA). The median age was 17 years (range, 6--9), and the median
      time between diagnosis and transplant 1 month (range, 1--4). Conditioning
      consisted of cyclophosphamide (50 mg/kg per day) on days--7 to--4 and
      antithymocyte globulin (30 mg/kg per day) on days--4 to--2 in nine patients.
      Total lymphoid irradiation was added to the preparative regimen for two. Graft
      versus-host disease (GVHD) prophylaxis consisted of cyclosporine A and
      prednisone. Median doses of CD34+ and CD3+ cells infused were 3.91 x 10(6) and
      0.3 x 10(6)/kg, respectively. The median time taken to achieve a neutrophil count
      >0.5 x 10(9)/l was 12 days and to recover a platelet count >20 x 10(9)/l, 13
      days. Two patients developed acute GVHD grade I--II and one developed limited
      chronic GVHD. There were two treatment-related deaths. At a median follow-up of
      44 months (range, 4--3), nine patients were alive with sustained and complete
      engraftment. This is a promising procedure in patients with AA, resulting in a
      rapid hematopoietic recovery, a low transplant-related mortality, and a low
      incidence of GVHD.

PMID- 15968277
TI  - Short- and long-term haematological surveillance of healthy donors of allogeneic
      peripheral haematopoietic progenitors mobilized with G-CSF: a single institution
      prospective study.
AB  - Healthy allogeneic donors, who were treated with G-CSF and underwent peripheral
      blood haematopoietic precursor collection at our Institution, were enrolled in a
      short- and long-term haematological surveillance protocol for a 5--7--year
      period. To date, 94 donors have been assessed with a mean follow-up of 30 months
      (4--84); for 30 subjects, the follow-up is >or=48 months. During G-CSF
      administration, 23/94 donors showed a significant platelet count decrease from
      the baseline. Pre-apheresis platelet decrement correlated with the total G-CSF
      dose administered, baseline platelet level and donor age. Normal platelet counts
      returned within 4--8 months. PMN and/or lymphocyte lower values were observed in
      55/94 donors 2 weeks after G-CSF administration, with mean drops from the
      baseline of 40 and 36% for PMN and lymphocytes, respectively. The PMN decrease
      correlated inversely with donor age, as younger donors were more affected than
      older ones, whereas the lymphocyte decrease correlated directly with the total
      blood volumes processed in the apheresis courses, in particular for donors
      subjected to large volume leukaphereses. Long-term observation showed moderate
      neutrophil reduction (25% count drop from the baseline) in four of the 30 donors
      observed for four years or more. 14 donors showed persistent, slight
      lymphocytopenia (mean drop of 13%) until the third year, with recovery in the
      fourth year of follow-up.

PMID- 15968278
TI  - Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation:
      outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the
      GETH (Grupo Espanol de Trasplante Hemopoyetico).
AB  - In order to analyze the outcome of patients with chronic myeloid leukemia (CML)
      who relapse after allogeneic stem cell transplantation (SCT), we investigated
      data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%)
      patients were treated after relapse; 36 out of 49 that failed to achieve a
      response received a second relapse-treatment, and seven a third one. At the last
      follow-up, the number of patients in molecular or cytogenetic remission was 29
      and 13, respectively. Overall survival and progression-free survival after
      relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years,
      respectively. In multivariate analysis, survival was significantly related to CML
      phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from
      transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a
      better survival compared with patients with one or two adverse features (65 vs 35
      vs 0%, respectively). We conclude that a significant proportion of CML patients
      that relapse after transplantation can regain complete and long-lasting
      remissions with one or more salvage therapies. Disease stage at relapse and time
      from transplant to relapse should be taken into account when comparing results of
      different salvage treatments.

PMID- 15968279
TI  - Establishment and properties of fetal dermis-derived mesenchymal stem cell lines:
      plasticity in vitro and hematopoietic protection in vivo.
AB  - Human mesenchymal stem cells (hMSCs) are excellent candidates for ex vivo gene
      transfer and cell therapy in various systems. However, hMSCs are mortal somatic
      cells, and thus invariably enter an irreversible growth arrest after a finite
      number of cell divisions in culture. It has been proposed that this is due to
      telomere shortening. In this study, pGRN145 plasmid containing human telomerase
      reverse transcriptase (hTRT) was introduced into fetal dermis-derived hMSCs.
      Single-cell clones positive for telomerase activity and hTRT mRNA were selected
      and expanded. Single-cell-derived hTRT(+) cells could be expanded rapidly in
      vitro and passaged up to 70 doublings without showing senescence. FACScan flow
      cytometer showed that hTRT(+) cells were positive for CD29, CD44, CD105, and
      CD166, while CD31, CD45, CD34, vWF, and HLA-DR were negative. Under suitable
      conditions, hTRT(+) cells have the ability of multiple lineage differentiation,
      including bone, fat, and nerve. Furthermore, transplantation of hTRT(+) cells
      could protect NOD/SCID mice from lethal irradiation. Thus, these cells may be an
      ideal cell source for promoting hematopoietic recovery after radiotherapy.

PMID- 15968281
TI  - Features of the metabolic syndrome present in survivors of bone marrow
      transplantation in adulthood.

PMID- 15968282
TI  - West Nile Virus encephalopathy in an allogeneic stem cell transplant recipient:
      use of quantitative PCR for diagnosis and assessment of viral clearance.

PMID- 15968283
TI  - Role and cost efficacy of unrelated cord blood in adult hematopoietic stem
      transplantation.

PMID- 15968284
TI  - Tumor antigen immunization of sibling stem cell transplant donors in multiple
      myeloma.
AB  - The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted
      by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy.
      Our objective was to induce tumor-specific T-cell immunity in bone marrow
      transplant (BMT) donors to enhance antitumor effects of allografts. We vaccinated
      five HLA-matched sibling donors with myeloma Id proteins isolated from recipient
      plasma before bone marrow harvest. Recipients were administered booster Id
      immunizations following transplantation. Vaccination induced donor Id and carrier
      specific cellular and/or humoral immune responses. Two recipients died within 30
      days of BMT from transplant-related complications. Id and carrier-specific T-cell
      responses were detected in all three remaining patients post-, but not pre-BMT
      and persisted for 18 months. All three surviving patients converted from partial
      to complete responses following BMT. Two of the three patients remain disease
      free 7 years and 8 years after BMT, and the third died of renal failure after 5.5
      years while in complete remission from myeloma. Our results suggest that myeloma
      Id vaccination induces specific T-cell immunity in healthy donors which may be
      transferable by BMT, is associated with prolonged disease-free survival of
      recipients, and may represent a general strategy to enhance graft-versus-tumor
      effect in other malignancies for which defined tumor-specific antigens exist.

PMID- 15968285
TI  - Unrelated donor bone marrow transplantation for 100 pediatric patients: a single
      institute's experience.
AB  - In all, 100 unrelated donor bone marrow transplantations (UD-BMT) were performed
      in our institute between October 1993 and January 2003. Of 93 evaluable patients,
      73 patients had hematological malignancy, 13 had nonmalignancy and seven had
      lymphoproliferative disease. The estimated 9-year event-free survival (EFS) rate
      was 57.1+/-5.5% in all patients. In the following analyses of the patients with
      hematological malignancy, the standard group had significantly better EFS than
      the high-risk group (61.5+/-7.0 vs 35.6+/-9.7%, P=0.02), and the EFS rate of the
      tacrolimus (FK-506)+methotrexate (MTX)+/-methylprednisolone prophylactic group
      for graft-versus-host disease was superior to that of the FK-506 without MTX
      group (75.7+/-8.0 vs 55.8+/-7.6%, P=0.02). When we compared the EFS rates of the
      FK506+MTX+/-methylprednisolone (mPSL) group and the HLA-matched related donor BMT
      group in our institute, these were almost similar (75.7+/-8.1 vs 68.4+/-9.3%).
      Therefore, UD-BMT using FK-506+MTX+/-mPSL is a safe and useful method for
      children with hematological malignancy who require allogeneic BMT.

PMID- 15968286
TI  - Monitoring oral cyclosporine therapy.

PMID- 15968287
TI  - Single centre experience of umbilical cord stem cell transplantation for primary
      immunodeficiency.
AB  - Primary immunodeficiencies (PID) are an important cause of childhood mortality.
      Haematopoietic stem cell transplantation (HSCT) is the best treatment for many
      PID. Umbilical cord stem cells are an alternative source of HSC. There is little
      data regarding outcome of umbilical cord stem cell transplantation (UCSCT) for
      PID. Our single centre experience is reported. A retrospective study of 14 of 148
      patients transplanted for PID, who have received 15 UCSCT was performed, with
      specific regard to graft-versus-host disease (GvHD) and immune reconstitution.
      Eight patients with severe combined immunodeficiency (SCID), and six with other
      combined immunodeficiencies were treated. Of the patients, 12 received unrelated
      cords, and two had sibling transplants. Median age at transplant was 3.5 months,
      median nucleated cell dose was 0.8 x 10(8)/kg. All engrafted. Median time to
      neutrophil engraftment was 22 days, median time to platelet engraftment was 51
      days. One developed significant grade III GvHD post transplantation. In total, 11
      patients had full donor T and six full donor B-cell chimerism, six of nine
      patients >1 year post-BMT had normal IgG levels and specific antibody responses
      to tetanus and Hib vaccines; two are being assessed. Two patients died of multi
      organ failure related to pre-existing infection and inflammatory complications
      respectively. UCSCT should be considered for patients requiring stem cell therapy
      for PID.

PMID- 15968288
TI  - Bone mineral density in children with thalassaemia major: determining factors and
      effects of bone marrow transplantation.
AB  - Osteoporosis and osteopenia affect up to half of patients with thalassaemia major
      (TM). We investigate the effects of acquired factors and BMT on bone mineral
      density (BMD) in these patients. In all, 53 patients on regular transfusion (BT
      group) and 33 patients at 5.7+/-1.9 years post transplant (BMT group) were
      recruited. BMD was measured by dual energy X-ray absorptiometry. Serum
      concentrations of osteocalcin, bone-specific alkaline phosphatase (ALP), beta
      crossLap and urinary cross-linking deoxypyridinoline (DPD) were measured by
      chemiluminescence and enzyme immunoassay, respectively. Severe BMD deficit (Z
      score <-2.5) at spine and hip were noted in 62 and 35% of BT group. Serum
      osteocalcin (beta=-0.463; P=0.006) was predictive of spine BMD, whereas age
      (beta=-0.843; P=0.007) and urine DPD (beta=-0.439; P=0.037) were associated with
      hip BMD in BT group. Among BMT patients, post transplant duration (beta=0.450;
      P=0.009) and serum bone-specific ALP (beta=-0.495; P=0.013) were associated with
      spine BMD. Severe BMD deficit was less common among BMT than BT patients (6 vs
      35%; P=0.036). The mean (s.d.) osteocalcin levels in BMT and BT groups were 96.4
      (72.7) microg and 68.9 (40.3) microg/l, respectively (P=0.037). In conclusion,
      severe BMD deficit is common in Chinese TM patients and BMT may reverse BMD
      deficit in these patients.

PMID- 15968289
TI  - Autoimmune thyroid dysfunction after hematopoietic stem cell transplantation.

PMID- 15968290
TI  - First-line thalidomide-dexamethasone therapy in preparation for autologous stem
      cell transplantation in young patients (<61 years) with symptomatic multiple
      myeloma.
AB  - Thalidomide-dexamethasone therapy was given in patients (<61 years) with
      previously untreated symptomatic multiple myeloma. The aim of this study was to
      assess the efficacy and toxicity of this combination as first-line therapy, and
      to determine its effect on stem cell collection and engraftment. During first
      line therapy, thalidomide and dexamethasone were administered for 75 days (200
      mg/day) and 3 months, respectively. The monthly dose of dexamethasone was 20
      mg/m2/day for 4 days, with cycles repeated on days 9 to 12 and 17 to 20 on the
      first and the third month of therapy. After first-line therapy, a collection of
      peripheral blood stem cells (PBSC) was performed. Between May 2003 and September
      2004, 60 patients were included. On an intent-to-treat basis, the overall
      response (> or =partial response) rate was 74%, including 24% of patients who
      obtained a complete remission. Grade 3-4 toxicities consisted of infections
      (12%), deep-vein thrombosis (3%), constipation (5%), and neuropathy (5%). A total
      of 58 patients (96%) proceeded to PBSC mobilisation and yielded a median number
      of 8 x 10(6) CD34+ cells/kg. First-line thalidomide-dexamethasone therapy is
      effective and relatively well tolerated in young patients with symptomatic
      multiple myeloma. This combination does not affect PBSC mobilisation.

PMID- 15968291
TI  - Early emergence of PNH-like T cells after allogeneic stem cell transplants
      utilising CAMPATH-1H for T cell depletion.
AB  - CAMPATH-1H (C-1H) is widely used in vivo and / or in vitro for T cell depletion
      in hematopoietic SCT. This humanised monoclonal antibody is specific for CD52, a
      marker coexpressed on the majority of human lymphocytes with CD48 and other
      glycosylphosphatidyl-inositol (GPI) anchored proteins. We detected CD52 / CD48
      dual expression on >99% of CD3(+) lymphocytes from normal individuals and all 15
      post-SCT patients whose transplants did not utilise C-1H. By contrast, 23 / 26
      patients with transplants involving C-1H (in vivo, in vitro or both) exhibited
      populations lacking CD52 expression that accounted for 49.7% (4.2-86.2%) of the
      CD3+ lymphocytes (median and range) in samples evaluated at a median of 2 months
      post-SCT. Most CD52- cells also lacked CD48 expression. These GPI- T cells were
      of either donor or mixed donor / recipient origin. They were predominant in the
      early months after SCT at times of profound lymphopenia and inversely correlated
      with the recovery of the absolute lymphocyte count (r= - 0.663, P<0.0001). The
      presence of CD52- cells has been correlated previously with clinical outcome
      after CAMPATH therapy for both malignant and nonmalignant diseases.

PMID- 15968292
TI  - Successful treatment of JMML with related bone marrow transplantation after
      reduced-intensity conditioning.

PMID- 15968293
TI  - Anti-CD25 monoclonal antibody (basiliximab) for prevention of graft-versus-host
      disease after haploidentical bone marrow transplantation for hematological
      malignancies.
AB  - Haploidentical donors are available for most patients who need allografts but do
      not have matched donors. However, GVHD, rejection, delayed immune reconstitution,
      and infections have been significant barriers. We designed a haploidentical BMT
      protocol focusing on prevention of GVHD and rejection. A total of 53 leukemic
      patients underwent haploidentical G-CSF-primed BMT without ex vivo T-cell
      depletion. GVHD prophylaxis consisted of antithymocyte globulin, cyclosporine,
      methotrexate, and mycophenolate mofetil. In all, 38 patients (the CD25 group)
      received additional anti-CD25 monoclonal antibody basiliximab. The results were
      compared to 15 patients who did not receive basiliximab. All patients achieved
      trilineage engraftment with full-donor chimerism. The incidence of acute II-IV
      GVHD was 11% in the CD25 group vs 33% in the control group (P=0.046). The overall
      incidence of extensive chronic GVHD was 15%. T, B, and NK cells recovered within
      12 months post transplant. The disease-free survival at 2 years was 53% with a
      median follow-up of 31 months. In conclusion, G-CSF primed haploidentical BMT
      along with sequential immunosuppressive agents as described here deserves further
      study.

PMID- 15968294
TI  - Isolation in the allogeneic transplant environment: how protective is it?
AB  - Aggressive infection control measures that include isolating patients within
      protective hospital environments have become a standard practice during
      allogeneic stem cell transplantation. A wide range of interventions includes the
      management of ventilation systems, BMT unit construction and cleaning, isolation
      and barrier precautions, interactions with health-care workers and visitors, skin
      and oral care, infection surveillance, and the prevention of specific nosocomial
      and seasonal infections. However, many of these practices have not been
      definitively proven to provide patients the intended benefit of decreased
      infection rates or improved survival. Furthermore, each intervention comes with a
      financial and social cost. With institutional cost containment efforts and recent
      trials suggesting that patients may be safely cared for in the outpatient
      environment after allogeneic transplantation, many widely held practices in
      managing the transplant environment are being reconsidered. With changing
      practices, transplant teams are encouraged to review local patterns of infections
      and associated complications and communicate regularly with infection control
      committees for guidance on the evolution of isolation needs for the
      immunosuppressed patient.

PMID- 15968295
TI  - Low-dose methotrexate for the treatment of graft-versus-host disease after
      allogeneic hematopoietic stem cell transplantation.
AB  - Methotrexate (MTX) is commonly used in the prophylaxis of graft-versus-host
      disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo
      HSCT). In order to evaluate the efficacy and safety of low-dose MTX treatment in
      patients with GVHD after allo-HSCT, 38 patients with acute GVHD (aGVHD), chronic
      GVHD (cGVHD) or GVHD post-donor lymphocyte infusion (post-DLI GVHD) after allo
      HSCT received intravenous MTX at a dose of 5 or 10 mg every 5-- days until a
      complete or partial response was seen, or there was treatment failure or
      intolerable side effects. The overall response rate was 94.7% (18/19 patients) in
      patients with aGVHD, 76.2% (16/21 patients) in patients with cGVHD and 2/2 in
      patients with post-DLI GVHD. The response rate for GVHD involving various organs
      was 100% in skin, 75% in gut, 55.6% in liver, 75% in mouth and 100% in the eye,
      among all enrolled patients. Side effects were minor. Short-term, low-dose MTX is
      a tolerable and an effective regimen for patients with aGVHD, cGVHD or post-DLI
      GVHD after allo-HSCT.

PMID- 15968296
TI  - Safety and potential efficacy of low-dose methotrexate for treatment of chronic
      graft-versus-host disease.
AB  - Low-dose methotrexate (MTX) is widely used in autoimmune diseases because of its
      anti-inflammatory activity. We report here the results of a retrospective study
      to review the outcomes of low-dose MTX used for treatment of refractory chronic
      graft-versus-host disease GVHD, with the goal of reducing the amount of
      prednisone needed to control the disease. In all, 14 patients with refractory
      chronic GVHD received MTX at a dose of 7.5 mg/m(2)/weekly for 3--0 weeks. Also,
      11 patients had skin involvement, often with scleroderma or fasciitis. The median
      duration of chronic GVHD at the start of MTX was 38 (range 1--35) months. In this
      retrospective review, we found no grade 3-- toxicities, and none of the patients
      needed blood transfusion or growth factors. In 10 patients (71%), GVHD could be
      adequately controlled with prednisone at doses below 1 mg/kg every other day
      without the addition of other agents. Four patients decreased the amount of
      concomitant immunosuppressive treatment, five continued with the same regimen,
      four required an increase in immunosuppressive treatment, and one decided to
      discontinue all treatment. From this preliminary analysis, MTX appears to be a
      well-tolerated, inexpensive and possibly steroid-sparing agent that is worthy of
      further evaluation in prospective trials for treatment of chronic GVHD.

PMID- 15968297
TI  - The course of bone mineral density and biochemical markers of bone turnover in
      early postmenopausal spinal cord-lesioned females.
AB  - STUDY DESIGN: A prospective observational study. OBJECTIVE: To evaluate bone
      mineral density (BMD) and biochemical markers of bone turnover in spinal cord
      lesioned females in the early postmenopausal period. SETTING: Clinic for Spinal
      Cord Injuries, H:S Rigshospitalet, Denmark. MATERIAL: In all, 18 early
      postmenopausal females with spinal cord lesions (SCL) of more than 2 years
      duration were recruited. In total, 11 completed the study. METHODS: Using dual
      energy X-ray absorption, BMD of the lumbar spine, femoral neck, trochanter and
      proximal tibia was measured every 6 months for 30 months. Biochemical markers of
      bone turnover in blood and urine were collected at the same time points. RESULTS:
      A significant increase in markers of bone formation in the blood was found and
      markers of bone resorption in urine tended to increase. BMD values changed
      insignificantly but for all regions decreased, except the lumbar spine.
      CONCLUSION: An accelerated bone turnover occurs in early postmenopausal SCL
      females. At the same time, we showed an insignificant decrease in BMD data from
      the lower extremity.

PMID- 15968298
TI  - The effects of body-weight supported treadmill training on cardiovascular
      regulation in individuals with motor-complete SCI.
AB  - STUDY DESIGN: Four-month longitudinal within-subject exercise training study.
      OBJECTIVE: Although body-weight supported treadmill training (BWSTT) has not
      shown promise as a means of improving ambulation in individuals with motor
      complete spinal cord injury (SCI), it may still improve cardiovascular health and
      function in this population. The purpose of this study was to (i) investigate the
      effects of BWSTT on peripheral muscular and elastic artery dimension and function
      and measures of heart rate variability (HRV) and blood pressure variability (BPV)
      in individuals with motor-complete SCI, and (ii) to make a preliminary
      examination of what factors may predict favourable cardiovascular outcomes
      following BWSTT in this population. SETTING: Centre for Health Promotion and
      Rehabilitation, McMaster University, Hamilton, Ontario, Canada. METHODS: Six
      individuals (four male, two female; age 37.7+/-15.4 years) with chronic SCI (C4
      T12; ASIA A-B; 7.6+/-9.4 years post-injury) were included in the present
      investigation. Doppler ultrasound was used to determine femoral (exercising;
      muscular), carotid (elastic) and brachial (non-exercising control; muscular)
      artery dimension and function before and after 4 months of BWSTT. Continuous
      heart rate and blood pressure were also recorded before and after 4-months of
      BWSTT to determine frequency domain measures of HRV and BPV; clinically valuable
      indices of neurocardiac and neurovascular control, respectively. RESULTS: Two-way
      ANOVA (vessel x time) revealed no exercise-induced change in femoral or carotid
      artery cross-sectional area, blood flow or resistance and no change in carotid
      artery compliance following the 4 months of BWSTT compared to the non-exercising
      control brachial artery. However, there was a significant exercise-induced
      increase in femoral artery compliance. There were no exercise-induced changes in
      HRV or BPV when all participants were considered together. However, the results
      suggest that the subgroup of individuals who had a substantial heart rate
      response to BWSTT (n=3), experienced exercise-training induced changes in HRV
      reflective of a relative shift toward cardiac vagal predominance and reductions
      in BPV. CONCLUSIONS: BWSTT may cause an increase in femoral artery compliance in
      individuals with motor-complete SCI and therefore, should be encouraged as a
      means of improving cardiovascular health in this population. BWSTT may also cause
      modest improvements in measures of HRV and BPV in a select subgroup of
      individuals who respond to ambulation with moderate to large increases in HR. In
      the present study, factors associated with a substantial HR response to BWSTT
      were a propensity to orthostatic intolerance and muscular spasticity.

PMID- 15968299
TI  - Chronic pain in individuals with spinal cord injury: a survey and longitudinal
      study.
AB  - STUDY DESIGN: Cross-sectional and longitudinal postal survey. OBJECTIVES: To (1)
      compare the severity of pain in persons with spinal cord injury (SCI) to national
      norms, (2) examine the association between pain and measures of (a) psychological
      functioning, (b) community integration and (c) pain interference with daily
      activities, and (3) examine the change in the prevalence and intensity of pain
      over time. SETTING: Community. METHODS: A total of 147 adults with SCI were
      surveyed twice, 2-6 years apart. Main outcome measures included presence/absence
      of pain in general and at specific body sites, 0-10 numerical rating scale of
      average pain intensity, modified Brief Pain Inventory Pain Interference scale, SF
      36 Bodily Pain scale, SF-36 Mental Health scale, Community Integration
      Questionnaire. RESULTS: Pain was more severe, on average, in this sample of
      patients with SCI than it is in normative samples. The presence of pain was
      associated with trends towards poorer psychological functioning and social
      integration, and the intensity of pain was associated with interference with a
      number of important basic activities of daily living. Little systematic change
      was found in pain over a 2-6-year-period, although there was evidence that the
      prevalence of shoulder pain increases over time. CONCLUSION: The current findings
      underscore the serious nature of pain in persons with SCI and provide additional
      support for the need to identify effective treatments for SCI-related pain.

PMID- 15968300
TI  - Energy expenditure during rest and treadmill gait training in quadriplegic
      subjects.
AB  - STUDY DESIGN: The analysis of oxygen uptake (VO(2)) and energy consumption in
      quadriplegics after 6 months of treadmill gait with neuromuscular electrical
      stimulation (NMES). OBJECTIVES: To compare metabolic responses in quadriplegics
      after 6 months of treadmill training, with NMES (30-50% body weight relief), with
      quadriplegics who did not perform gait. SETTING: Ambulatory of University
      Hospital, Brazil. METHODS: Quadriplegics were separated into gait and control
      groups (CGs). On inclusion, all subjects performed VO(2) test. In the gait group
      (GG) (n=11), the protocol consisted of 8 min of rest, 10 min of treadmill walking
      using NMES and 10 min of recovery. In the CG (n=10), testing consisted of 8 min
      rest, 15 min of quadriceps endurance exercise in sitting position with NMES and
      10 min recovery. VO(2), carbon dioxide production (VCO(2)) and energy consumption
      were measured. The GG performed 6 months of treadmill training, using NMES, for
      20 min, twice a week. The CG did not practice any activity with NMES, performing
      conventional physiotherapy only; the CG was stimulated only during the
      cardiorespiratory test. RESULTS: All parameters increased significantly for the
      GG: 36% for VO(2) (l/min), 43% for VCO(2) (l/min) and 32.5% for energy
      consumption (J/kg/s). For the CG, during knee extension exercise, VO(2) increased
      without changes in the energy consumption (P<0.05); smaller values were obtained
      for all parameters when compared to those obtained during gait. CONCLUSIONS:
      Quadriplegic gait was efficient towards increasing VO(2) and energy consumption,
      which can decrease the risk of cardiovascular diseases.

PMID- 15968301
TI  - Retroperitoneal lymphocele associated with lumbar spine fracture: report of an
      unusual case.
AB  - DESIGN: To describe a case of retroperitoneal lymphocele as an extremely rare
      complication after lumbar spine fracture. OBJECTIVE: To discuss the possible
      mechanism of development of retroperitoneal lymphocele following blunt trauma to
      the ureter and lumbar spine. SETTING: Fukui University Hospital, Fukui, Japan.
      RESULTS: A 71-year-old man presented with severe intractable low back pain caused
      by a huge retroperitoneal lymphocele, which was considered to be related to an
      occult L4 vertebral fracture and a blunt ureteral injury. The retroperitoneal
      lymphocele also caused significant instability at L3-4 level, thus requiring
      surgical resection followed by interbody fusion. CONCLUSION: Physicians should be
      aware that such unusual retroperitoneal lymphocele might develop even after a
      blunt ureteral injury or a minor lumbar spine fracture.

PMID- 15968302
TI  - Body weight supported treadmill training in acute spinal cord injury: impact on
      muscle and bone.
AB  - DESIGN: Longitudinal prospective case series. OBJECTIVE: To evaluate the impact
      of early introduction post-spinal cord injury (SCI) of twice-weekly body-weight
      supported treadmill training (BWSTT) on muscle and bone. SETTING: Centre for
      Health Promotion and Rehabilitation, McMaster University, Canada. METHODS: Five
      individuals who had sustained traumatic SCI within 2-6 months participated in the
      study. Bone mineral densities (BMD) of proximal femur, distal femur, proximal
      tibia and lumbar spine were measured before and after training, as well as muscle
      cross-sectional area (CSA), BMD and bone geometry at mid-femur and proximal
      tibia. Serum osteocalcin and urinary deoxypyridinoline were measured at baseline,
      and after 24 and 48 sessions of training. RESULTS: All participants experienced
      increased muscle CSAs, ranging from 3.8 to 56.9%. Reductions in BMD were evident
      in all participants at almost all lower limb sites after training, ranging in
      magnitude from -1.2 to -26.7%. Lumbar spine BMD changes ranged from 0.2 to -7.4%.
      No consistent changes were observed in bone geometry. BWSTT did not alter the
      expected pattern of change in bone biochemical markers over time. The individual
      with the greatest improvement in ambulatory ability demonstrated the smallest
      reduction in lower limb BMD. Conversely, the individual who completed the fewest
      BWSTT sessions demonstrated the greatest reductions in BMD. CONCLUSIONS: Twice
      weekly BWSTT appeared to partially reverse muscle atrophy after SCI, but did not
      prevent bone loss. Larger, controlled trials should evaluate whether relative
      preservation of bone loss occurs with regular BWSTT following acute SCI.
      SPONSORSHIP: Ontario Neurotrauma Foundation.

PMID- 15968303
TI  - Pin-site myiasis: a rare complication of halo orthosis.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report a rare complication following
      halo placement for cervical fracture. SETTING: United States University Teaching
      Hospital. CASE REPORT: A 39-year-old woman who sustained a spinal cord injury
      from a C6-7 fracture underwent halo placement. She subsequently developed an
      infection adjacent to the right posterior pin, which then became infected with
      Diptera larvae (maggots), necessitating removal of the pin and debridement of the
      wound site. CONCLUSION: Halo orthosis continues to be an effective means of
      immobilizing the cervical spine. Incidence of complications ranges from 6.4 to
      36.0% of cases. Commonly reported complications include pin-site infection, pin
      penetration, pin loosening, pressure sores, nerve injury, bleeding, and head ring
      migration. Pin-site myiasis is rare, with no known reports found in the
      literature. Poor pin-site care by the patient and her failure to keep follow-up
      appointments after development of the initial infection likely contributed to the
      development of this complication.

PMID- 15968304
TI  - Effects of electrically induced muscle contraction on flexion reflex in human
      spinal cord injury.
AB  - STUDY DESIGN: Flexion reflex study in motor complete human spinal cord injury
      (SCI). OBJECTIVES: To examine changes in the magnitude of the flexion reflex
      following functional electrical stimulation (FES) of the rectus femoris (RF)
      muscle. SETTING: Bioengineering Unit, University of Strathclyde, Glasgow,
      Scotland, UK. METHODS: The flexion reflex was evoked by electrical stimulation of
      the sural nerve, and was recorded in the tibialis anterior (TA) muscle. RF muscle
      conditioning stimulation was performed at 0.7, 1, and 2 times motor threshold ( x
      MT) over a range of conditioning test intervals. RESULTS: The incidence of the
      early component of the flexion reflex (<100 ms) was low, suggesting that this
      reflex component might be suppressed in SCI. The long latency flexion reflex
      component (>120 ms) was observed in all subjects during control conditions and
      following sensorimotor conditioning. FES applied to the RF muscle (above and
      below MT) in the main induced a significant early and long lasting depression of
      the long latency flexion reflex. CONCLUSION: The depression of the flexion reflex
      was a result of multisensory actions on flexion reflex pathways resulting from
      the direct and indirect (mechanical) consequences of electrically induced muscle
      contraction on cutaneous and muscle afferents. Our findings emphasize the
      importance of sensory feedback mechanisms in modulating flexion reflex
      excitability, and highlight the need for rehabilitation professionals to consider
      the central actions of FES-induced afferent feedback when incorporating FES into
      a rehabilitation program. SPONSORSHIP: State Scholarships Foundation (IKY) of
      Hellas.

PMID- 15968305
TI  - Neuromyelitis optica.
AB  - The combination of optic neuritis and myelitis, the so-called Neuromyelitis
      optica is an uncommon pattern of demyelinating disorder. In 1870, Sir Thomas
      Clifford Allbutt first reported the association and Erb published a comparable
      report. Gowers and Dreschfeld described other instances in the 19th century. This
      paper attempts to review the syndrome to consider whether it merits recognition
      as a disease, sui generis, or rather as a syndrome symptomatic of multiple
      sclerosis, acute disseminated encephalomyelitis, and other immunological
      disorders. Two forms are distinguished: a monophasic illness, and a relapsing
      form. The claimed differential features separating it from classical multiple
      sclerosis are appraised. Modern immunology suggests an antibody-dependent,
      complement-mediated pathogenesis.

PMID- 15968306
TI  - Calcified intervertebral disc herniation in a child with myelopathy treated with
      laminoplasty.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a case of pediatric calcified
      intervertebral disc herniations at the cervical-thoracic junction surgically
      treated with laminoplasty. METHODS: A 13-year-old girl with calcified
      intervertebral disc herniations at C7/Th1 and Th1/2 causing myelopathy was
      performed with laminoplasty . RESULTS: Postoperative course was without
      complication, and the neurologic examination returned to a completely normal
      state at 5 years to date after surgery. CONCLUSIONS: Laminoplasty produced an
      excellent result and is a consideration for treatment of similar cases of
      calcified intervertebral disc herniation.

PMID- 15968307
TI  - Clinical and economic consequences of volume- or time-dependent intermittent
      catheterization in patients with spinal cord lesions and neuropathic bladder.
AB  - STUDY DESIGN: Open comparative study. OBJECTIVE: To compare the impact of volume
      dependent intermittent catheterization (VDIC) and time-dependent intermittent
      catheterization (TDIC) on financial burden and clinical outcomes in patients with
      spinal cord lesions (SCL). SETTING: Department of Spinal Rehabilitation,
      Loewenstein Rehabilitation Hospital, Israel. METHOD: Economic and clinical
      outcomes were examined in 13 SCL patients treated with VDIC following bladder
      volume measurement by a portable ultrasound device (the study group), and in 11
      patients treated with TDIC (the control group). Patients were followed for 12-30
      days. Costs were calculated according to December 2003 prices at Loewenstein
      Hospital. The t-test and the Fisher's Exact Test were employed for comparisons
      between the groups. RESULTS: The number of catheterizations per patient per day,
      the time required to perform volume measurements and catheterizations, and their
      total cost, were approximately 44, 49, and 46% lower in the study group than in
      the control group. SCIMU (representing bladder management functioning) increased
      during the study in both groups, and the increase was 31% higher in the study
      group than in the control group. Urinary infection was found in three patients in
      the control group and in none in the study group. CONCLUSION: VDIC has economic
      and probably also clinical advantages over TDIC.

PMID- 15968308
TI  - [Allogeneic hematopoietic stem cell transplantation for treatment of Philadelphia
      chromosome positive acute lymphoblastic leukemia].
AB  - OBJECTIVE: To explore the optimal time of allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) applied in patients with Philadelphia chromosome
      positive acute lymphoblastic leukemia (Ph+ ALL), and the optimum order of donor
      selection. METHODS: From Mar 2000 to Jul 2004, 32 patients with Ph+ ALL were
      treated by Allo-HSCT, and the follow up ended at Dec 30.2004 with medium of 13
      months. Of whom, 24 were male, and 8 were female. Twenty-three patients have been
      transplanted in CR1, 9 patients beyond CR1 (1 in CR2, 8 in refractory or relapse
      status). Twelve cases received HSCT from identical sibling donor, 4 unrelated
      Cord Blood Transplantation (CBT), 3 HSCT from matched unrelated donor (MUD), and
      13 HSCT from mismatched related donor (MMRD), of which, 6 cases were M(BCR/ABL)
      subtype, and 20 m(BCR/ABL) subtype. The Kaplan-Meier method was used to estimate
      the probabilities of leukemia-free survival (LFS), overall survival (OS) and
      relapse incidence (RI), and the factors were compared by means of the Log-rank
      test. Simultaneous effect of multiple covariates were estimated with Cox model.
      RESULTS: Of all the 32 cases engrafted, 4-year OS was 57.19%, LFS 37.09%, and RI
      56.36%. In univariate prognostic analysis model, the OS was higher in CR1 group
      pre-HSCT than that in non-CR1 group (74.50% vs 22.22%, P=0.0046), LFS was higher
      (49.06% vs 11.11%, P=0.0057), RI was lower (44.80% vs 84.76%, P=0.0157); the OS
      was higher in M(BCR/ABL) group than that in m(BCR/ABL) group (100% vs 40.91%,
      P=0.0318), LFS was higher (75% vs 17.72%, P=0.0057), RI was lower (25% vs 77.88,
      P=0.0116); OS was similar in HLA MM RD group to that in HLA identical group
      (52.65% vs 55.56%, P=0.6247), LFS was similar (45.12% vs 30.00%, P=0.8315), and
      RI was also similar (50.77% vs 60.62%, P=0.8217). In multiple covariate analysis
      model, the BCR/ABL type was the risk factor of LFS [P=0.005, Exp(B)=9.971] and RI
      (P=0.006, Exp(B)=9.488), the status of disease pre-HSCT and BCR/ABL subtype was
      the risk factor of OS [P was 0.010 and 0.038, Exp(B) was 4.532 and 37.537
      respectively]. CONCLUSION: We had better do HSCT in CR1 to treat Ph+ ALL, if
      patient is refractory to chemotherapy, we can try STI571, and HSCT should be done
      as soon as possible if the patients get CR. Mismatched related donor is
      considered as regular donor for Ph+ ALL patients without identical donors. We
      should pay more attention to monitoring and prophylaxis of relapse in m(BCR/ABL)
      patients after HSCT.

PMID- 15968309
TI  - [Role of molecular screening for common fusion genes in the diagnosis and
      classification of leukemia].
AB  - OBJECTIVE: To assess the value of common fusion genes analysis in the diagnosis
      and classification of leukemia by multiplex RT-PCR. METHODS: The multiplex RT
      PCR, including 8 parallel PCR reactions, could screen 86 mRNA breakpoints or
      splice variants at the same time, which was important for the diagnosis and
      prognosis of leukemia. Bone marrow samples from 161 cases of leukemia and 8 cases
      of myelodysplastic syndrome (MDS) were involved in the study. The distribution of
      common fusion genes in leukemia was analyzed by the method mentioned above in
      combination with clinical and morphological features. RESULTS: Ten fusion genes
      were detected in 115 cases of leukemia, including AML1/ETO, PML/RAR alpha,
      PLZF/RAR alpha, dupMLL, MLL/AF6, MLL/AF10, CBFbeta/MYH11, BCR/ABL, Hox11, and
      EVI1 BCR/ABL was positive in all the 52 cases of chronic myeloid leukemia;
      PML/RAR alpha was found in 21 of 25 acute promyelocytic leukemia (APL), and
      PLZF/RAR alpha was detected in one case of APL. Sixteen cases of 17 AML1/ETO
      positive acute leukemia (AL) belonged to FAB-M2 subtype, and one case was mixed
      leukemia. Three of 4 AL cases carrying CBFbeta/MYH11 were M4 subtype, and one was
      M5 subtype. MLL aberrations were found in 16 AL, in which all MLL/AF6
      translocation existed in M5 subtype with classic monoblastic characters.
      Furthermore, BCR/ABL was detected in 5 acute lymphoblastic leukemia (ALL) cases.
      Fusion genes were also found in 2 MDS cases, of which AML1/ETO positive-MDS-RAEB
      progressed to AML rapidly. CONCLUSION: Screening of common fusion genes by
      multiplex RT-PCR is an important tool which could provide useful and reliable
      molecular genetic information for the diagnosis and treatment of leukemia.

PMID- 15968310
TI  - [An in vitro study of cytotoxic and antineoplastic effect of Solanum nigrum L
      extract on U266].
AB  - OBJECTIVE: To study cytotoxicity and antineoplastic effect in vitro Solanum
      nigrum L extract on U266. METHODS: U266 cells were cultured together with the
      extract of Solanum nigrum L. Cytotoxicity assay was tested by CCK-8. Cell cycle
      and apoptosis were determined using flow cytometry (FCM) analysis. RESULTS:
      Extract of Solanum nigrum L showed strong cytotoxicity against U266 cells. The
      IC50 was about 117 mg/L. After exposure of U266 cells to the drug for 48 hours,
      the cell cycle distribution was changed compared with the controls. There was
      decrease of cells in the G0/G1 phase with increase of cells in the S phase and
      G2/M phase. Apoptosis of U266 cells could be shown with staining of Annexin V
      FITC/PI or TFAR19 testing through FCM. The proportion of apoptotic cells
      increased in parallel with the increase of the drug dosage. CONCLUSION: Solanum
      nigrum L extract showed strong cytotoxicity effect on U266 cells. The
      antineoplastic effect of the drug can partly be ascribed to its apoptotic
      inducing effect.

PMID- 15968311
TI  - [Analysis of characteristics of 72 cases of t(8;21) acute myeloid leukemia].
AB  - OBJECTIVE: To investigate the laboratorial and clinical characteristics of
      t(8;21) AML, and to compare the differences between patients with additional
      chromosomal abnormalities and those without additional aberrations. METHODS:
      Seventy-two cases of t(8;21) AML were analyzed retrospectively, including
      features of morphology, initial blood cells, cytogenetic G-banding karyotype,
      immunophenotype, AML1/ETO fusion gene and clinical outcome. In order to compare
      the characteristics of patients with additional chromosomal abnormalities with
      those with t(8;21) alone, these patients were divided into two groups according
      to their karyotype as follows: Group A included patients with t(8;21) alone;
      Group B included patients with additional aberrations. RESULTS: According to FAB
      classification, there were 65 cases of M2, 5 cases of M4 and 2 of M5.
      Cytogenetically, 45 cases (62.5%) were accompanied by additional chromosomal
      abnormalities. The main additional aberrations included -Y, +4, del(9q). There
      were no obvious differences between these two groups in their features of age
      distribution, bone marrow blast cells, Auer rods, eosinophilia, immunophenotype,
      as well as central nervous system leukemia occurrence and complete remission rate
      of induction, but a male prevalence and a lower initial WBC were observed in
      Group B. With a follow up of 1-96 months, the median survival time was much
      longer in group A (65 months) compared with group B (12 months), but there was no
      difference between the four main subgroups of group B. The estimated 3-year
      survival was (63.9+/-11.2)% in group A compared with (20.9+/-9.2)% in group B.
      CONCLUSION: Additional chromosomal abnormality is an adverse factor for prognosis
      of t(8;21) AML. The median survival time of patients with additional aberrations
      was much shorter than that of those without.

PMID- 15968312
TI  - [Relation between the expression of sIL-2R and the relapse in patients with acute
      lymphoblastic leukemia].
AB  - OBJECTIVE: To explore the relation of the serum level of sIL-2R in relapse
      patients with acute lymphoblastic leukemia (ALL). METHODS: With ELISA, we
      determined the levels of sIL-2R of 48 patients with ALL after their first
      diagnoses, complete remission 1 and relapse. The levels of sIL-2R of 30 patients
      from complete remission 1 to relapse were monitored. RESULTS: The levels of sIL
      2R were higher in the relapse group and first diagnosed group than in the
      control. The levels of sIL-2R were higher in the relapse group and first
      diagnosed group than in the complete remission 1 group. However, the difference
      between the complete remission 1 and the control had no statistical significance.
      When we determined the levels of sIL-2R dynamically, we found that after complete
      remission, the levels of sIL-2R decreased, however, before one month of
      hematological relapse, the levels of sIL-2R increased. CONCLUSION: Monitor of the
      level of sIL-2R can predict impending relapse of patients with ALL and is helpful
      to early diagnosis of relapse.

PMID- 15968313
TI  - [Analysis of CT antigen expression and humoral immunogenicity of NY-ESO-1 protein
      in gastric carcinoma].
AB  - OBJECTIVE: To study the expression of 11 cancer-testis (CT) genes and autologous
      humoral immune response to NY-ESO-1 in gastric carcinoma in China to provide some
      data for developing a vaccine against this cancer. METHODS: Pathology tests were
      conducted in 101 gastric carcinoma samples, including tumor tissue and paired
      adjacent normal non-tumor tissue. Reverse transcription-polymerase chain reaction
      (RT-PCR) was used to test for 11 CT antigen gene expression and ELISA for
      autologous humoral immune response to NY-ESO-1. The antigen of NY-ESO-1 was also
      detected in tumor tissues by mAb E978 in IHC. RESULTS: About 74.3% of the samples
      expressed at least one CT antigen, and the most frequently expressed one was MAGE
      3 (41.6%). Twelve out of the 101 samples (11.9%) were found to be NY-ESO-1 mRNA
      positive. Simultaneously, autologous humoral immune response to NY-ESO-1 was
      detected in 6 of 12 NY-ESO-1 mRNA positive patients. CONCLUSION: Multiple CT
      genes were expressed in gastric cancer samples. MAGE-3, SSX-1, SSX-4, NY-ESO
      1/LAGE-1, and MAGE-1 can be chosen as candidate antigens for cancer vaccines due
      to their higher expression rate. The potential of a multivalent CT antigen
      vaccine, including NY-ESO-1 and MAGE-3 along with other CT antigens, should be
      evaluated in patients with gastric cancer.

PMID- 15968314
TI  - [Promoter hypermethylation of the p16 gene in pre- and post-gastrectomy plasma of
      patients with gastric adenocarcinoma].
AB  - OBJECTIVE: To detect promoter hypermethylation of the p16 gene in pre- and post
      operative plasma, matched cancer tissues and para-tumor non-cancerous tissues of
      patients with gastric adenocarcinoma for evaluating the effectiveness of
      therapeutic intervention. METHODS: Primary tumor tissues and para-tumor tissues
      and preoperative plasma samples of 84 patients with gastric adenocarcinoma were
      collected, and 14-21 days' post-operative plasma of 30 of the 84 patients who
      underwent curative gastrectomy was available. Plasma of 15 healthy people was
      also collected as control. After sodium-bisulfite treatment, extracted DNA was
      amplified for p16 promoter hypermethylation by methylation-specific polymerase
      chain reaction (MSP). The PCR products were detected by both gel-ethidium bromide
      electrophoresis and high performance liquid chromatogram (HPLC). RESULTS: Among
      the samples from 84 patients, p16 hypermethylation was detected in 26 (31.0%)
      cancer tissues and 2 (0.02%) para-tumor non-cancerous tissues and 12 (14.3%)
      preoperative plasma, while plasma of the healthy people was negative. In all
      positive plasma, the paired primary tumor tissues were also confirmed to be
      methylated. As far as samples from 30 patients with post-operative plasma were
      concerned, 14 cancer tissues and 6 preoperative plasma samples were positive, and
      only 1 of 6 post-operative plasma remained hypermethylated. The results detected
      by HPLC exactly matched those by gel-ethidium bromide electrophoresis.
      CONCLUSION: Promoter hypermethylation of the p16 gene detected in plasma consists
      with that in primary cancer tissues of patients with gastric adenocarcinoma. The
      alteration of status of hypermethylation of p16 in post-operative plasma is
      considered the consequences of surgical intervention. HPLC can be used as an
      efficient tool in detecting the product of MSP.

PMID- 15968315
TI  - [Expression of proline-rich tyrosine kinase-2 (Pyk2) in gastric carcinoma and its
      significance].
AB  - OBJECTIVE: To investigate whether proline-rich tyrosine kinase-2 (Pyk2) is
      expressed differently in normal gastric mucosas and gastric carcinoma tissues and
      further to evaluate its significance. METHODS: Expressions of Pyk2 in 59 cases of
      normal gastric mucosas and 52 cases of gastric carcinoma tissues were analysed by
      immunohistochemical methods. RESULTS: Immunohistochemical studies showed that the
      positive rates of Pyk2 protein expression in normal gastric mucosas and gastric
      carcinoma tissues were 86.44% (51/59) and 19.23% (10/52) respectively. The
      difference between normal gastric mucosas and gastric carcinoma tissues was
      statistically significant (P<0.05). The positive rates of Pyk2 expression in
      highly differentiated gastric carcinoma and moderately/lowly differentiated
      gastric carcinoma were 47.37% (9/19) and 3.03% (1/33) respectively. Statistically
      significant differences (P<0.05) were observed in the levels of Pyk2 expression
      between highly differentiated gastric carcinoma and moderately/lowly
      differentiated gastric carcinoma. The positive rates of Pyk2 expression at
      different TNM stages gastric carcinoma were respectively: stage I 66.67% (6/9),
      stage II 30% (3/10), stage III 3.45% (1/29), stage IV 0% (0/4). The differences
      were statistically significant [(II+III+IV) v I, chi2=15.767, P<0.05].
      CONCLUSION: In this study, we demonstrate that Pyk2 is expressed in normal
      gastric mucosas, whereas its expression declines significantly or almost
      disappears in gastric carcinoma tissues. The expression of Pyk2 progressively
      decreases with increasing grade of malignancy and TNM stages of gastric
      carcinoma. This phenomenon indicates that Pyk2 expression may be involved in the
      generation and development of gastric carcinoma.

PMID- 15968316
TI  - [Role of tissue factor in the invasion of cultured human colon carcinoma cells
      and its correlation with matrix metalloproteinases].
AB  - OBJECTIVE: To investigate the role of tissue factor expression in the invasive
      ability of human colon carcinoma cells and to analyze the correlation between
      tissue factor and MMP-2 and MMP-9. METHODS: HT-29 cells with sense-TFcDNA
      transfection and LoVo cells with antisense-TFcDNA transfection were implanted
      subcutaneously into nude mice as well as controls. The expressions of MMP-9 and
      MMP-2 at the protein and mRNA levels were detected by Western blot and RT-PCR
      respectively; Gelatin zymography was used for assay of the MMP-9 and MMP-2
      activities in the supernatant cultured media of LoVo cells with antisense-TFcDNA
      transfection and controls. RESULTS: The expressions of MMP-9 and MMP-2 at the
      protein and mRNA levels in the group of HT-29 cells with sense-TFcDNA were
      significantly increased with untransfected HT-29 cells. The expression in the
      group of LoVo cells with antisense-TFcDNA had a significant decrease than that of
      the controls. The MMP-9 and MMP-2 activities of LoVo cells with antisense-TFcDNA
      were weakened because of the lower expression of tissue factor by gelatin
      zymography. The expression of MMP-9 and MMP-2 were closely correlated to the
      expression of tissue factor. CONCLUSION: Tissue factor can increase the invasive
      ability of human colon carcinoma cells. The partial mechanism is that TF can
      upregulate the expressions of MMP-9 and MMP-2. Tissue factor may be an inner
      agonist in the secretion of MMPs in colon carcinoma cells.

PMID- 15968317
TI  - [Expression of metabolic enzymes of fluoropyrimidines in primary colorectal
      cancer and its clinical significance].
AB  - OBJECTIVE: To investigate the expression of metabolic enzymes of
      fluoropyrimidines in primary colorectal cancer. METHODS: Sixty-one cases of
      pathological confirmed primary colorectal cancer were collected in Beijing Cancer
      Hospital from August 2003 to February 2004. The expressions of thymidylate
      synthase (TS), dihydropyrimidine dehydrogenase (DPD) and orotate phosphoribosyl
      transferase (OPRT) were detected in paired tumor tissues and non-cancerous
      tissues by RT-PCR. RESULTS: Expression of each enzyme in tumor tissues was
      positively correlated with that in paired non-cancerous tissues respectively.
      Compared with the expression of each enzyme in cancer with that in non-cancer,
      OPRT was higher in cancer while that of DPD and TS was comparable. The expression
      of OPRT was approximately 4.38-folds higher in colorectal cancer tissues than
      that in non-cancerous tissues (P=0.000). The lowest expression of OPRT was found
      in mucinous carcinoma while the highest levels in poorly-differentiated
      adenocarcinoma. There were correlations between the ratio of tumor tissues/non
      cancerous tissues OPRT expression (T/N) and metastasis to the lymph nodes
      (r=0.36; P=0.005), small vessel invasion (r=0.26; P=0.041) and differentiation
      (r=-0.33; P=0.009). CONCLUSION: The detection of three enzymes by means of RT-PCR
      is practical and can be used in clinical application. Our results also suggest
      that OPRT is a potential biomarker in predicting prognosis of colorectal cancer.

PMID- 15968319
TI  - [Regulation of genistein on the levels of ERalpha, ERbeta mRNA in uterine
      endometrial cancer cells].
AB  - OBJECTIVE: To explore the mechanism of phytoestrogen (genistein) on uterine
      endometrial cancer cells and provide the theory foundation for using
      phytoestrogen in clinical practice. METHODS: Uterine endometrial cancer cell
      lines (ishikawa) were cultured in vitro at different genistein concentration, and
      the expressions of the two estrogen subtypes of endometrial cancer cells were
      observed by real-time PCR. And two treatment groups, estradiol and progestin,
      were used as positive controls. RESULTS: (1) Low concentration of genistein could
      enhance the expression level of ERalpha mRNA of endometrial cancer cells, which
      was obviously weaker than that of the estradiol group. On the other hand, low
      concentration of genistein could decrease the expression level of ERbeta mRNA of
      endometrial cancer cells, however estradiol had hardly any effect on this. (2)
      High concentration of genistein could decline the expression levels of ERalpha
      and ERbeta mRNA of endometrial cancer cells, whose effect was weaker than that of
      progestin. CONCLUSION: The expression levels of ERalpha mRNA and ERbeta mRNA of
      endometrial cancer cells vary with genistein concentrations. The experimental
      results suggest that genistein may act as estrogen receptor regulator.

PMID- 15968318
TI  - [Inhibitory effect of doxazosin on the growth of transplanted tumor of prostate
      cancer cell PC-3 in nude mice].
AB  - OBJECTIVE: To investigate the effects of alpha1 adrenoceptor antagonist doxazosin
      on the growth of androgen-independent prostate cancer cell PC-3 transplanted in
      nude mice. METHODS: PC-3 cells xenografts were transplanted (s.c.) in nude mice,
      and thirty xenografts were established successively. They were then randomly
      divided into 5 groups: A (control group), B (doxazosin 3 mg/kg), C (doxazosin 10
      mg/kg), D (doxazosin 30 mg/kg), and E (doxazosin 100 mg/kg). Seven days after
      implantation, doxazosin was administered in sterile water by oral gavage, and the
      volumes of the transplanted tumors were measured during the therapy twice a week.
      All the mice were sacrificed after two weeks of doxazosin administration; the
      tumors were resected to do the following research. Immunohistochemistry of Ki67
      and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling
      (TUNEL) was done to study the effects of doxazosin on the proliferation and
      apoptosis of prostate cancer cells; moreover, we also used Western blotting to
      study the protein expression of Smad-4 and IkappaB alpha. RESULTS: Nude mouse
      experiments showed that the in vivo doxazosin administration induced a notable
      decrease in the volumes of prostate cancer xenografts compared with the control
      group, and the tumor weights were also decreased. Interestingly enough,
      administration of doxazosin at higher concentrations (10, 30, 100 mg/kg) did not
      have further effect on tumor suppression. The percentage of PC-3 TUNEL positive
      cells was significantly higher than that of the control group; while the
      doxazosin treated groups and the control group did not have statistical
      difference on the percentage of Ki67 positive cells. In doxazosin treated groups
      Smad-4 and IkappaB alpha expressions were higher than that of the control group.
      CONCLUSION: Doxazosin can inhibit the growth of the prostate xenografts in the
      nude mice by inducing apoptosis without affecting the cell proliferation.
      Activation of transforming growth factor beta1 (TGF-beta1) signaling pathway may
      be the mechanism underlying doxazosin-mediated apoptosis.

PMID- 15968320
TI  - [Regulation of orphan receptor ERR alpha by estrogen and progesterone in
      endometrial carcinoma cell line].
AB  - OBJECTIVE: To explore the relationship between expression of ERR alpha mRNA and
      estrogen and progesterone and to elucidate the function of ERR alpha in
      endometrial carcinoma. METHODS: The expression of ERR alpha mRNA was examined by
      reverse transcription polymerase chain reaction. Endometrial carcinoma cell line
      Ishikawa was dealt with different concentrations of 17beta-estradiol (10(-10)
      mol/L, 10(-8) mol/L and 10(-6) mol/L) for 15 min, 30 min and 24 h and 17beta
      estradiol and ER inhibitor-ICI182780 were given concomitantly to observe the
      change of ERR alpha mRNA. Different concentrations of progesterone (10(-8) mol/L,
      10(-7) mol/L, 10(-6) mol/L and 10(-5) mol/L) were also given to Ishikawa cell
      line for 24 h to observe the change of ERR alpha mRNA. RESULTS: The expression
      level of ERR alpha mRNA was slightly higher than that of the control group after
      being stimulated for 15 min, 30 min and 24 h by 10(-10) mol/L 17beta-estradiol.
      However the expression level of ERR alpha mRNA was significantly lower than that
      of the control group after being stimulated for 15 min, 30 min and 24 h by 10(-8)
      mol/L and 10(-6) mol/L of 17beta-estradiol. When 10(-6) mol/L of ICI182780 and
      10(-8) mol/L of 17beta-estradiol were given simultaneously to Ishikawa cell line,
      this down-regulation was blocked. After being stimulated for 24 h by 10(-7)
      mol/L, 10(-6) mol/L and 10(-5) mol/L of progesterone, the expression levels of
      ERR alpha mRNA were significantly higher than that of the control group, but no
      change was found in 10(-8) mol/L of progesterone. CONCLUSION: 17Beta-estradiol
      can down-regulate the expression of ERR alpha mRNA and this regulation is
      mediated by estrogen receptor. Progesterone can up-regulate the expression of ERR
      alpha mRNA.

PMID- 15968321
TI  - [Effects of estrogen, progestin and mifepristone on endometrial carcinoma cell
      lines].
AB  - OBJECTIVE: To study the effects of estrogen, progestogen and mifepristone on
      endometrial carcinoma cell lines in vitro. METHODS: The well-differentiated
      endometrial cancer cell line Ishikawa and moderate-differentiated endometrial
      cancer cell line Hec-1B were cultured in vitro. The cells were divided into four
      groups: control, estrogen, estrogen and progestogen, estrogen and progestogen and
      mifepristone, then we implanted cells in 96-well plates to search the response in
      distinct hormones. RESULTS: When stimulated by estrogen for 72 hours, the growth
      of Ishikawa cells was significantly higher than the control, Hec-1B cells only
      grew higher than the control, but it was no significance in statistics.
      Progestogen inhibited Ishikawa cells significantly after being stimulating for 72
      hours, there was the same effect on Hec-1B cells after being stimulating for 96
      hours. On the base of estrogen and progestogen, we added mifepristone, cells
      developed after 96 hours in Ishikawa cells and cells developed after 48 hours in
      Hec-1B cells. CONCLUSION: Estrogen can cause endometrial carcinoma cell growth;
      progestogen inhibits the hyperplasia induced by estrogen; mifepristone
      antagonizes the effect of progestogen on cell growth.

PMID- 15968322
TI  - [Study of clinical value of dual-phase imaging using single photon emission
      computed tomography with coincidence detection for differentiating benign from
      malignant lesions].
AB  - OBJECTIVE: To investigate the clinical value of dual-phase imaging of 18F-fluoro
      2-deoxy-D-glucose (18F-FDG) using single photon emission computed tomography with
      coincidence detection (SPECT with coincidence) for differentiating benign and
      malignant lesions. METHODS: Thirty patients with unknown lesions from June 2003
      to March 2004 in our hospital were enrolled in this study. All patients underwent
      dual-phase imaging of 18F-FDG SPECT with coincidence. The early images were
      obtained 60 min post injection. And the patients were divided into 2 groups, one
      receiving delayed scans at 210 min after 18F-FDG injection and the other at 270
      min. Lesion status was determined by pathologic findings or by clinical follow
      up. RESULTS: Forty-eight lesions (30 malignant and 18 benign lesions verified by
      pathologic findings or clinical follow-up) of 30 patients were detected by dual
      phase imaging, in which there were 29 true positive results, 15 true negative, 3
      false positive and 1 false negative. The sensitivity, specificity, accuracy,
      positive predictive value and negative predictive value of dual-phase imaging
      were 96.7%, 83.3%, 91.6%, 90.6%, and 93.8%, respectively. Those of early imaging
      and CT were 93.3%, 72.2%, 85.4%, 84.8%, 86.7% and 76.9%, 57.1%, 70.0%, 76.9%,
      57.1%, respectively. The T/NT of all malignant lesions (except 1 false negative
      case) in delayed imaging were significantly increased (t=-3.071, P<0.01).
      However, there were no statistical differences in the T/NT of benign lesions
      (t=0.398, P=0.695) between early and delayed imagings. CONCLUSION: Dual-phase
      imaging of FDG SPECT with coincidence provides benefit for differentiating benign
      and malignant lesions.

PMID- 15968323
TI  - [Efficacy of radiofrequency ablation of 343 patients with hepatic tumor and the
      relevant complications].
AB  - OBJECTIVE: To investigate the treatment efficacy of radiofrequency ablation (RFA)
      of hepatic tumors and the relevant complications. METHODS: A total of 343
      patients with 778 hepatic tumors underwent ultrasound-guided RFA (582
      procedures). There were 212 cases of hepatic cellular carcinoma (HCC) with 448
      tumors, and the average largest diameter was 4.0 cm. Of all the patients, 63
      (29.7%) were in the stage of I-II (UICC Systems) and 149 (70.3%) in stage of III
      IV (including 43 patients with tumor recurrence after surgical resection). There
      were 131 cases of metastatic liver carcinoma (MLC), with 330 metastases in the
      liver, the average diameter was 3.9 cm, and the liver metastases of 91 patients
      (69.5%) came from gastrointestinal tract. The patients were treated using the
      relatively standard protocol. Crucial attention must be paid to monitoring the
      abnormal changes in ultrasound images as well as the vital signs of the patients
      to find the possible hemorrhage and peripheral structure injury in time. The
      tumors were considered ablated successfully if no viability was found on enhanced
      CT within 24 hours or 1 month after RFA. The patients were followed up for 2-62
      months. RESULTS: The ablation success rate for HCC was 95.5% (428/448 tumors),
      and the rate for MLC was 96.4% (318/330 tumors). The local tumor recurrence rates
      for HCC and MLC were 8.5% (38/448 tumors) and 11.8% (39/330 tumors),
      respectively. A total of 138 patients (40.2%) underwent repeated ablations for 2
      11 times because of tumor recurrence or metastasis. The first, second and third
      years survival rates were 87.7%, 67.4% and 56.8% for HCC patients, 81.6%, 50.8%
      and 27.2% for MLC patients, respectively. The survival rate from 63 early-stage
      HCC patients were 92.9%, 82.8% and 74.5%, respectively. The major complication
      rate in this study was 2.4% (14 of 582 procedures). The complications which
      consisted of mechanical and thermal injuries usually occurred during or shortly
      after the RFA treatment. There were 5 hemorrhages, 1 colon perforation, 5
      injuries of adjacent structures, 2 bile leakages and 1 skin burn. CONCLUSION:
      RFA, as a minimally invasive local treatment, has become an effective and
      relatively safety alternative for the patients of hepatic tumors, even of
      advanced live tumor, tumor recurrence, liver metastases which are unresectable or
      difficult to treat with traditional therapies. Knowledge about possible
      complications and their control may increase the treatment efficacy and help to
      promote the use of RFA technique.

PMID- 15968324
TI  - [Characterization of the interaction between low density lipoprotein receptor
      related protein-associated protein 1 and the cancer and embryo expression protein
      65].
AB  - OBJECTIVE: To understand the mechanism of cancer and embryo expression protein 65
      (CEP65) in cancer development. METHODS: CEP65 was used as a bait protein to
      isolate the partners of CEP65 from a human placenta cDNA library with yeast two
      hybrid system. The DNA fragments from positive clone were expressed prokaryotic
      and mammalian cells respectively, the GST pull-down experiment was performed to
      ascertain the binding activity. RESULTS: After screening a human placenta cDNA
      library, the low density lipoprotein receptor-related protein-associated protein
      1 (RAP) was isolated and shown to interact with CEP65. GST pull-down assay
      results indicated that His-CEP65 and GST-RAP expressed by prokaryotic system were
      immunoprecipitated, and so were Myc-RAP and GST-P65 expressed by mammalian cells.
      CONCLUSION: RAP can interact with CEP65 and RAP may be a candidate to mediate the
      function of CEP65.

PMID- 15968325
TI  - [Relationship between LAPTM4B gene polymorphism and susceptibility of lung
      cancer].
AB  - OBJECTIVE: To investigate the possible association between the allelic variation
      of LAPTM4B and the genetic susceptibility of lung cancer. METHODS: The genotype
      of LAPTM4B was analyzed in 134 unrelated healthy adult individuals and 166
      patients with lung cancer by utilizing polymerase chain reaction based on special
      primers. The genotypical distribution of LAPTM4B was analyzed by chi2 test.
      RESULTS: The allelic frequencies of the *2 were 40.1% and 28.0% in the lung
      cancer group and the healthy control group respectively, which was significantly
      different between the two groups (P=0.002). There was a significant difference in
      the overall genotypical distribution between the patients and the controls
      (P=0.005). The risk of suffering from lung cancer was increased 1.91 times in the
      individuals of the *1/2 genotype (95%CI: 1.178-3.110) and 3.26 times in the
      individuals of the *2/2 genotype of LAPTM4B (95%CI: 1.338-7.929) compared with
      the *1/2 genotype. No association was observed between the genotypical
      distribution of LAPTM4B and the clinical information on patients of lung cancer
      such as gender, age, pathological type, differentiation classification of TNM and
      infection of HBV. CONCLUSION: This study suggests that the allele *2 of LAPTM4B
      might be the risk factor of lung cancer, which could be associated with genetic
      susceptibility of lung cancer.

PMID- 15968326
TI  - [Selective heterologous communication among human lung epithelial cells,
      fibroblasts, and lung cancer PG cells].
AB  - OBJECTIVE: To further understand the roles of gap junctional intercellular
      communication in carcinogenesis and progression of human lung cancer. METHODS:
      The heterologous communication was characterized among human lung epithelial
      cells HLEC, human lung fibroblasts HLF, human lung giant carcinoma PG cells and
      its Cx43 transfectants PG/C4 by using a preloading assay. Cx43 immunofluorescent
      staining and Northern blot were performed to examine Cx43 gene expression.
      RESULTS: Although both human lung fibroblasts HLF and epithelial cells HLEC
      expressed Cx43 and had very strong homologous communication, HLEC cells were
      unable to communicate with HLF cells. The human lung carcinoma cell line PG was
      defective of both homologous communication, and heterologous communication with
      its epithelial origin HLEC. Transfection of Cx43 into PG cells, which rescued PG
      cells' homologous communication and enhanced heterologous communication with HLF
      cells, could restore heterologous coupling with HLEC cells. CONCLUSION: Selective
      heterologous communication exists among different kinds of human lung cells, when
      human lung carcinoma cells lost coupling with its epithelial origin, Cx43 gene
      expression is not enough to establish heterologous communication between them.

PMID- 15968327
TI  - [Interleukin-6 is involved in the enhanced proliferation of HEK293 cells by the
      tumor specific antigen of HCA520].
AB  - OBJECTIVE: To investigate the effect of tumor specific antigen of HCA520 on the
      proliferation of HEK293 cells and to obtain some functional implications for
      HCA520. METHODS: MTT assay was performed with HEK293 stable cell lines
      transfected with pcDNA3-HCA520-flag construct. Cytokines probably involved in
      HCA520 enhanced proliferation were screened by RT-PCR, and effect of these
      cytokines on the HEK293 cell proliferation was further confirmed by MTT assay.
      RESULTS: HCA520 significantly promoted the proliferation of HEK293 cells, which
      was at least partially attributed to the up-regulation of IL-6 in HEK293 cells by
      HCA520. CONCLUSION: HCA520 might accelerate tumorigenesis by promoting
      proliferation of cancerous cells.

PMID- 15968328
TI  - [Effect of antisense epidermal growth factor receptor cDNA transfection on
      telomerase activity of glioblastomas cells].
AB  - OBJECTIVE: To study the effects of antisense epidermal growth factor receptor
      (EGFR) cDNA transfection on telomerase activity and telomere length of
      glioblastomas U87MG cells and the mechanism. METHODS: Glioblastoma U87MG cells,
      which over-expressed EGFR, were transfected with antisense-EGFR cDNA constructs.
      Several clones stably expressing lower or undetectable levels of EGFR protein
      were obtained. The effect of antisense-EGFR cDNA on telomerase activity was
      assessed by Telomeric Repeat Amplification Protocol (TRAP) assay. The effect of
      antisense-EGFR cDNA on telomere length was determined by Southern blot
      hybridization. The mRNA expressions of hTERT, hTEP1 and c-myc were analyzed by
      semi-quantitative PCR. RESULTS: U87MG cells that were transfected with antisense
      EGFR cDNA expressed lower level of EGFR and were less responsive to the growth
      stimulation of EGF compared with the control cells. Telomerase activity was
      significantly decreased in the antisense-EGFR clones. Telomere length was
      shortened. The mRNA expression of hTERT was slightly decreased in the antisense
      EGFR clones, whereas the expressions of hTEP1 and c-myc were not altered.
      CONCLUSION: Antisense-EGFR cDNA transfection can sufficiently inhibit EGFR signal
      transduction pathway, decrease telomerase activity and shorten telomere length,
      which may be a new mechanism of antisense-EGFR approach in tumor suppression. The
      down-regulation of hTERT mRNA may contribute to the decreased telomerase activity
      in the antisense-EGFR clones.

PMID- 15968329
TI  - [c-kit and PDGFRA mutations in 60 cases of gastrointestinal stromal tumors
      (GISTs)].
AB  - OBJECTIVE: To explore the status of activating mutations of c-kit and PDGFRA in
      GIST of Chinese patients. METHODS: Sixty GISTs, confirmed by immunoreactivity of
      CD117, CD34, SMA, S-100 and Desmin, were evaluated for the presence of c-kit
      exons 9, 11, 13 and 17 mutations, and PDGFRA exons 12 and 18 mutations. The PCR
      products were sequenced directly for mutations, using DNA extracted from paraffin
      embedded tissue. RESULTS: 53% of the tumors were located in the stomach, 22% in
      the small bowel, 8% in the colo rectum, 2% in the esophagus and 15% in the
      extragastrointestinal tract. Immunohistochemical demonstrations of c-kit (CD117)
      were seen in 90% cases. Overall, c-kit mutations were detected in 63.3% of
      patients as follows: 58.3% in exon 11, 3.3% in exon 9, 1.7% in exon 13 and none
      in exon 17. The types of c-kit exon 11 mutations were mostly heterogeneous and
      clustered in the classic "hot spot" at the 5' end of exon 11, 42.9% being point
      mutation and in-frame deletion at Codon 557-560. 14.3% of cases showed internal
      tandem duplications (ITD) at the 3' end of exon 11 in a region of a second hot
      spot for c-kit mutations. Interestingly, these cases were associated with female
      predominance, stomach location and occurrence in older patients. The present
      study failed to identify a significant association between c-kit mutation status
      and risk of aggressive behavior in GISTs. Exon 9 mutations consisted of ITP of
      six nucleotides encoding Ala-Tyr. A new point mutation of L641P was revealed in
      exon 13. PDGFRA mutations were found in 5% of all the 60 cases with none of the
      positive cases expressed detectable KIT protein. The type of mutation was the
      commonest point mutation of D842V of exon 18. CONCLUSION: Most KIT expressing
      GIST show c-kit mutations that are preferentially located within the classic hot
      spot of exon 11. A second hot spot -ITD at the 3' end of exon 11 seems to
      associate with a subgroup of gastric GISTs in older females. c-kit exons 9, 13
      and 17 mutations are rare events in GIST of China. PDGFRA oncogenic mutations are
      more likely seen in KIT-negative GISTs arising in the peritoneal surface and have
      an unfavorable clinical course.

PMID- 15968330
TI  - [Detection of EWS-WT1 fusion transcripts in paraffin-embedded tissues for
      desmoplastic small round cell tumor].
AB  - OBJECTIVE: To detect the EWS-WT1 chimeric mRNA in desmoplastic small round cell
      tumor (DSRCT) and its clinicopathological significance. METHODS: Formalin fixed,
      paraffin-embedded tumor specimens from 4 examples of this entity were studied by
      reverse transcriptase polymerase chain reaction to detect the EWS-WT1 fusion
      transcripts resulting from the chromosomal translocation t(11;22)(p13;q12). The
      following tumor specimens were included as controls: 2 Ewing's sarcomas/primitive
      neuroectodermal tumors (PNET/ES), 2 alveolar rhabdomyosarcomas, and 2 lymphomas.
      RESULTS: EWS-WT1 fusion transcripts were detected in 3 of 4 desmoplastic small
      round cell tumors but not in any other tumor types studied as controls.
      CONCLUSION: The analysis of the EWS-WT1 fusion transcript which was performed on
      formalin-fixed, paraffin-embedded tissues is a sensitive and specific method in
      the diagnosis and differential diagnosis of DSRCT.

PMID- 15968331
TI  - [Neurolymphomatosis, a case report].
AB  - Neurolymphomatosis (NL) is characterized by lymphomatous infiltration of the
      peripheral nervous system. We report a case of neurolymphomatosis (NL) which was
      confirmed by sural nerve biopsy. Sural nerve specimen from a 49-year-old female
      patient with weakness of limbs was examined with routine histochemical and
      immunohistochemistry staining, in which the first antibodies against CD3, CD20,
      CD45, CD45RO and CD68 were used. Numerous T-lymphoma cells invaded in the adipose
      tissue of epineurium of sural nerve. The nerve biopsy showed marked axonal
      degeneration of myelinated fibers. The clinical and histopathologic findings
      confirmed the diagnosis of neurolymphomatosis.

PMID- 15968332
TI  - Advances in Hepatitis B Research: From Virology to Clinical Management (A Special
      Issue).

PMID- 15968333
TI  - Hepatitis B Virus e Antigen Variants.
AB  - More than 300 million people worldwide are chronically infected with hepatitis B
      virus (HBV). Considering the very short generation time for a virus, and the high
      error rate associated with the reverse transcription step of HBV replication,
      decades of HBV infection are probably equivalent to million years of human
      evolution. The most important selective force during the natural course of HBV
      infection appears to be the immune response. The development of anti-HBe antibody
      in hepatitis B patients usually correlates with reduction of HBV viremia. As a
      consequence, escape mutants of anti-HBe are selected. The core promoter mutants
      express less HBe antigen (HBeAg) through transcriptional down regulation, while
      precore mutants express truncated products. We recently identified additional
      mutations that modulate HBeAg translation initiation, proteolytic cleavage, and
      secondary structure maintenance through a disulfide bond. The core promoter
      mutants have been associated with the development of fulminant hepatitis during
      acute infection and liver cancer during chronic infection. Consistent with their
      enhanced pathogenicity, core promoter mutants were found to replicate at up to 10
      fold higher levels in transfected human hepatoma cells than the wild-type virus.
      Moreover, some core promoter mutants are impaired in virion secretion due to
      missense mutations in the envelope gene. These virological properties may help
      explain enhanced pathogenicity of core promoter mutants in vivo.

PMID- 15968334
TI  - Advances in Molecular Diagnosis of HBV Infection and Drug Resistance.
AB  - Serological markers are key elements in diagnosing acute hepatitis B virus (HBV)
      infection and determining its possible evolution towards chronicity. Once
      treatment of chronic HBV is initiated with approved anti-hepadnaviral agents,
      such as lamivudine, interferon-alpha, or adefovir dipivoxil, the measurement of
      HBV DNA in serum can not only help monitor treatment efficacy but also indicates
      breakthrough infection should drug resistance emerge. Advances in the molecular
      diagnosis of drug resistance using highly sensitive methodologies such as DNA
      hybridization assays can further pinpoint the type of mutation responsible and,
      more importantly, detect upcoming viral resistance at an early stage when the
      variant represents only a minor fraction of the total viral population. Such new
      tools are especially relevant for patients at high risk for disease progression
      or acute exacerbation. Recent diagnostic developments including HBV genotyping
      and precore/core promoter assays that could well play important future roles in
      HBV patient management are also reviewed.

PMID- 15968335
TI  - A Practical Approach to Management of Chronic Hepatitis B.
AB  - Chronic hepatitis B (CHB) is one of the important public health problems
      worldwide. Major advances have been made in the treatment of CHB during the past
      several years. This article systemically reviews advances in the application of
      HBV DNA quantitation and three approved drugs for HBV treatment, and presents an
      updated and practical clinical approach to managing CHB. Highly sensitive PCR
      based quantitation of HBV DNA makes it possible to precisely determine pre
      treatment HBV load and monitor HBV DNA response during treatment. HBV DNA level,
      HBeAg status, degree of hepatic histological activity and fibrosis, and serum
      transaminases are the most important parameters in determining indication,
      regimen, and duration of HBV treatment. Although interferon alfa-2b, lamivudine,
      and adefovir are all approved as initial HBV treatment, understanding the
      advantages and advantages of each agent is important in choosing the best
      treatment for each individual patient with CHB.

PMID- 15968336
TI  - Advances in immunomodulating therapy of HBV infection.
AB  - Patients with chronic hepatitis B virus (HBV) infection have a higher risk of
      developing liver cirrhosis and hepatocellular carcinoma. Interferon-alpha,
      lamivudine and adefovir dipivoxil are the three approved treatment for chronic
      HBV infection and offers the only means of preventing the development of these
      complications. However, the efficacy of these agents, in terms of loss of
      Hepatitis B e antigen with or without seroconversion to Hepatitis B e antibody,
      normalization of serum alanine transaminase levels, loss of serum HBV DNA, and
      improvement in liver histology can only be achieved in 20-30% of those treated.
      Long-term treatment with either lamivudine or adefovir dipivoxil can result in
      the development of drug resistant mutants leading to an increased length of
      treatment with additional nucleoside analogues. These limitations of the current
      antiviral therapies underline the need for alternative therapies. Specific and
      nonspecific immunotherapeutic strategies to restore effective virus-specific T
      cell responses in those with chronic HBV infection offers an interesting
      alternative approach. These immunotherapeutic therapies include the adoptive
      transfer of HBV immunity, pegylated interferon and therapeutic vaccine therapies.

PMID- 15968337
TI  - High level expression of apoptosis inhibitor in hepatoma cell line expressing
      Hepatitis B virus.
AB  - The serious result of hepatitis B (HBV) virus infection is development of
      hepatocellular carcinoma (HCC). However, the reason of development of HCC in HBV
      infected patients is still unclear. Recently, the suppression of cell apoptosis
      is found to relate with the development of cell carcinogenesis, therefore, the
      expression of apoptosis inhibitor in the virus related cancer line such as
      hepatoma cell line HepG2.215 was investigated. There are at least six Human
      apoptosis inhibitors (IAP) have been identified now. They are cIAP1, cIAP2, XIAP,
      NAPI, survivin and pIAP. Using gene-assay technology, we have recently compared
      the expression of IAPs in the HepG2.215 cells that persistently expresses
      Hepatitis B virus by integrated HBV genome with its parent cell line HepG2. The
      results suggest that there was obviously increase of cIAP2 and cIAP1 in the
      HepG2.215 cells versus HepG2 cells. Those observations imply a possibility of
      long time HBV infection could induce the over-expressing apoptosis inhibitors,
      furthermore, causing the liver cancer. The high expression of cIAP1 and cIAP2 in
      HBV expressing cells was confirmed by RT-PCR and Northern blot analysis. However,
      we did not find the change of NIAP and suvivin in HepG2.215 cells. In contrast,
      the expression of XIAP was down in the HepG2.215 cells comparing with HepG2
      cells. How HBV triggers the over-expression of apoptosis inhibitor is unclear.
      Transient transfection of HepG2 cells with the plasmids expressing different HBV
      proteins such as S, M, L, X and core proteins did not give a decisive conclusion.
      Further study is going on now.

PMID- 15968338
TI  - Natural History and Clinical Consequences of Hepatitis B Virus Infection.
AB  - Despite the existence of Hepatitis B vaccination, hepatitis B virus (HBV)
      infection is still prevalent worldwide and accounts for significant morbidity and
      mortality. It is encouraging that majority of patients do recover from the acute
      infection, however, those that progress to chronic disease state is at great risk
      of developing complications such as hepatocellular carcinoma, cirrhosis and liver
      failure. Hepatitis B virus infection can be influenced by many factors such as
      host immune status, age at infection, and level of viral replication. The
      discovery about the existence of various genotypes and its association with
      different geographic distribution as well as the knowledge regarding mutant
      species has aid us in better understanding the nature of HBV infection and in
      delivering better care for patients. It is especially important to recognize
      those individuals with HBeAg-negative chronic HBV as they have a poorer prognosis
      compare with their counterparts, HBeAg-positive. Tremendous progress has been
      made over the years in understanding the behavior and clinical course of the
      disease; however, the natural history of HBV is complex and we still have much to
      explore and learn.

PMID- 15968339
TI  - Management of HBV Infection in Liver Transplantation Patients.
AB  - In the absence of preventative therapy, reinfection of allografts with hepatitis
      B virus (HBV) after orthotopic liver transplantation (OLT) resulted in dismal
      allograft and patient survival. Major advances in the management of HBV-infected
      recipients of OLT during the past 15 years have steadily reduced the rate of
      reinfection, resulting in improved outcomes. Initially, long-term use of
      hepatitis B immune globulin (HBIG) as a source of anti-HBs antibodies was
      effective in preventing or delaying reinfection. Lamivudine monotherapy made it
      possible to suppress HBV replication prior to OLT, markedly decreasing the risk
      of reinfection. Although lamivudine monotherapy used before and after OLT could
      prevent reinfection, its effectiveness was limited by progressive development of
      lamivudine-resistant mutant infections. Combination therapy with HBIG and
      lamivudine after OLT reduced both HBV recurrence and the risk of lamivudine
      resistance even in patients with active HBV replication. Introduction of adefovir
      provided a safe, alternative oral antiviral able to treat effectively lamivudine
      resistant mutants HBV. Available strategies to prevent reinfection have resulted
      in OLT outcomes for HBV-infected patients comparable to those for patients
      transplanted for non-HBV indications. In the future, combination therapies of
      HBIG and both nucleoside and/or nucleotide agents will undoubtedly be optimized.
      Development of new drugs to treat HBV will increase opportunities to combine
      agents to enhance safety, efficacy and prevent emergence of HBV escape mutants.
      New vaccines and adjuvants may make it possible to generate anti-HBs in
      immunosuppressed patients, eliminating the need for HBIG.

PMID- 15968340
TI  - Epidemiology and Prevention of Hepatitis B Virus Infection.
AB  - Hepatitis B is one of the most common infectious diseases globally. It has been
      estimated that there are 350 million chronic hepatitis B virus (HBV) carriers
      worldwide. The prevalence of chronic HBV infection varies geographically, from
      high (>8%), intermediate (2-7%) to low (<2%) prevalence. HBeAg-negative chronic
      hepatitis B (e-CHB) and occult HBV infection are two special clinical entities,
      and the prevalence and clinical implications remain to be explored. The
      predominant routes of transmission vary according to the endemicity of the HBV
      infection. In areas with high HBV endemicity, perinatal transmission is the main
      route of transmission, whereas in areas with low HBV endemicity, sexual contact
      amongst high-risk adults is the predominant route. HBV has been classified into 7
      genotypes, i.e. A to G, based on the divergence of entire genome sequence and HBV
      genotypes have distinct geographical distributions. Three main strategies have
      been approved to be effective in preventing HBV infection. They are behavior
      modification, passive immunoprophylaxis, and active immunization. The implement
      of mass HBV immunization program is recommended by the WHO since 1991, and has
      dramatically decreased the prevalence of HBV infection and HCC in many countries.

PMID- 15968341
TI  - A folate-rich diet is as effective as folic acid from supplements in decreasing
      plasma homocysteine concentrations.
AB  - Background & Aims: At least 500 mug of folic acid are required daily to treat
      hyperhomocysteinemia. To reach this amount by dietary changes alone may be
      difficult because food has a low folic acid content and bioavailability. No
      studies have compared the effects of similar amounts of additional folate derived
      from a combination of folate-rich and fortified foods or folic acid from
      supplements on plasma total homocysteine (tHcy) concentrations, which was the aim
      of this study. Methods: Twenty male patients with hyperhomocysteinemia and
      coronary artery disease were included in a randomized, crossover intervention
      trial. Patients were treated daily with a combination of foods containing
      approximately 500 mug of folate or with one 500 mug capsule of synthetic folic
      acid over two five-week periods separated by a five-week wash-out period.
      Results: Plasma folate increased markedly (p<0.001) and plasma tHcy decreased
      (p<0.001) with both therapies. Folate-rich foods decreased tHcy by 8.6% (95% CI: 
      15.9 to -1.2) and synthetic folic acid capsules by 8% (95% CI: -13.3 to -2.7).
      Conclusions: This study shows, for the first time in the literature, that a
      folate-rich diet is as effective as folic acid capsules in decreasing plasma tHcy
      concentrations and adds further support to the recommendation of those diets to
      prevent cardiovascular disease.

PMID- 15968342
TI  - Cell Cycle Arrest by a Natural Product via G2/M Checkpoint.
AB  - CKBM is a natural product that exhibits a novel anti-tumor activity through the
      induction of cell cycle arrest and apoptosis. We have investigated its effects on
      cell cycle regulation using a gastric cancer cell line, AGS. The effects of CKBM
      on cell proliferation, cell cycle regulation and apoptosis were analyzed using
      BrdU (5-bromo-2'-deoxyuridine) cell proliferation assay and flow cytometric
      analysis, respectively. Specific cellular protein expressions were measured using
      Western blot analysis. Flow cytometric analysis indicated that CKBM induced G2/M
      cell cycle arrest and apoptosis, whereas differential protein expressions of p21,
      p53 and 14-3-3sigma (stratifin) using Western blot analysis were enhanced. The
      differential expressions of p21, p53 and 14-3-3sigma in AGS cancer cells after
      CKBM treatment may play critical roles in the G2/M cell cycle arrest that blocks
      cell proliferation and induces apoptosis.

PMID- 15968343
TI  - Study of urban community survey in India: growing trend of high prevalence of
      hypertension in a developing country.
AB  - The prevalence pattern of hypertension in developing countries is different from
      that in the developed countries. In India, a very large, populous and typical
      developing country, community surveys have documented that between three and six
      decades, prevalence of hypertension has increased by about 30 times among urban
      dwellers and by about 10 times among the rural inhabitants. Various factors might
      have contributed to this rising trend and among others, consequences of
      urbanization such as change in life style pattern, diet and stress, increased
      population and shrinking employment have been implicated. In this paper, we study
      the prevalence of hypertension in an urban community of India using the JNC VII
      criteria, with the aim of identifying the risk factors and suggesting
      intervention strategies. A total of 1609 respondents out of 1662 individuals
      participated in our cross-sectional survey of validated and structured
      questionnaire followed by blood pressure measurement. Results showed pre
      hypertensive levels of blood pressures among 35.8% of the participants in
      systolic group (120-139mm of Hg) and 47.7% in diastolic group (80-89 mm of Hg).
      Systolic hypertension (140 mm of Hg) was present in 40.9% and diastolic
      hypertension (90 mm of Hg) in 29.3% of the participants. Age and sex-specific
      prevalence of hypertension showed progressive rise of systolic and diastolic
      hypertension in women when compared to men. Men showed progressive rise in
      systolic hypertension beyond fifth decade of life. Bivariate analysis showed
      significant relationship of hypertension with age, sedentary occupation, body
      mass index (BMI), diet, ischemic heart disease, and smoking. Multivariate
      analysis revealed age and BMI as risk factors, and non-vegetarian diet as
      protective factor with respect to hypertension. Prevalence of prehypertensives
      was high among younger subjects - particularly students and laborers who need
      special attention. Role of non-vegetarian diet as a protective factor might have
      been related to fish-eating behavior of the sample population, who also use
      mustard oil as cooking medium - both of which have significant level of essential
      polyunsaturated fatty acids. The observed prevalence of hypertension in this
      study and other studies suggest the need for a comprehensive national policy to
      control hypertension in India, and, in other similar developing countries.

PMID- 15968344
TI  - Comparison of Classical and Clozapine Treatment on Schizophrenia Using Positive
      and Negative Syndrome Scale of Schizophrenia (PANSS) and SPECT Imaging.
AB  - Many neuroimaging studies of schizophrenia have shown abnormalities in the
      frontal cortex, limbic system, basal ganglia, temporal and parietal lobes. These
      findings are not specific or consistent enough to build up a coherent theory of
      the origin of the brain abnormality in schizophrenia. This paper describes a
      state-of-the-art approach of SPECT to correlate neuropsychological evaluation.
      PANSS scores and different brain focal abnormalities of two groups of patients
      receiving Clozapine and classical antipsychotic treatments were observed. A total
      of 20 drug-free patients, actively psychotic schizophrenic, were selected
      according to the DSM-IV criteria. Pre-Post-treatment was designed using PANSS and
      99mTc- ECD-SPECT to assess regional Cerebral Blood Flow (rCBF). The results
      showed that after treatment, differences in PANSS scores were significant in both
      groups, with superior scores resulting from the Clozapine therapy. Results were
      supported by SPECT, which showed a greater improvement in the Clozapine group.
      Both positive and negative symptoms were improved with Clozapine as well. Before
      treatment, hypofrontality was the most common (85%) finding, whereas after
      treatment hypofrontality was mostly cleared. However, in some areas like temporal
      and caudate, hyperfrontality was induced. Negative symptoms showed linkage to
      hypofrontality in both groups before and after treatment, and both positive and
      negative symptoms were improved more with Clozapine therapy than with classical
      treatment.

PMID- 15968345
TI  - An Avian Connection as a Catalyst to the 1918-1919 Influenza Pandemic.
AB  - The 1918 Influenza pandemic was one of the most virulent strains of influenza in
      history. This strain quickly dispatched previously held theories on influenza.
      World War One introduced new environmental stresses and speed of dissemination
      logistics never experienced by humans. In light of new phylogenic evidence the
      cause of this influenza outbreak is now being considered to have linkage to the
      avian influenza. Animals act as reservoirs for this influenza virus and research
      indicates the influenza virus often originates in the intestines of aquatic
      wildfowl. The virus is shed into the environment, which in turns infects domestic
      poultry, which in turn infects mammalian hosts. These animals, usually pigs, act
      as a transformer or converters; creating a strain that can more readily infect
      humans. Therefore swine can be infected with both avian and human influenza A
      viruses and serve as a source for infection for a number of species as the
      incidents of direct infection from birds to humans have been rare. Increased
      human habitation near poultry and swine raising facilities pose greater influenza
      outbreak risk. It was this combination of environmental factors that may have
      contributed to the greatest pandemic of recent times, and, moreover, similar
      conditions exist throughout Southeast Asia today.

PMID- 15968347
TI  - Responsive lanthanide luminescent cyclen complexes: from switching/sensing to
      supramolecular architectures.
AB  - This article highlights some of the recent developments in the use of responsive
      cyclen based lanthanide luminescent devices, focusing on Eu(III), Tb(III),
      Nd(III) and Yb(III) complexes, where the photophysical properties, such as the
      excited state lifetimes, quantum yield/intensity and emission polarisation are
      modulated by the local chemical environment, e.g. ions and molecules, or through
      self-assembly of either f-f or mixed f-d cyclen complexes.

PMID- 15968348
TI  - Synthesis of huge macrocycles using two calix[4]arenes as templates.
AB  - Macrocycles with up to 100 atoms have been synthesised using two calix[4]arenes
      as templates: first, (3,5-dialkenyloxy)phenyl groups are attached to the wide rim
      of a calix[4]arene via urea links, then the alkenyl groups are connected via a
      metathesis reaction using a tetratosylurea calix[4]arene for their correct
      prearrangement and finally the urea functions are cleaved to detach the newly
      formed macrocycles.

PMID- 15968349
TI  - Porous materials show superhydrophobic to superhydrophilic switching.
AB  - Switching between superhydrophobicity and superhydrophilicity in porous materials
      was predicted theoretically and demonstrated experimentally with the example of
      thermally induced contact angle change; tunability of this system was also
      demonstrated.

PMID- 15968350
TI  - [{(Mo)Mo5O21(H2O)3(SO4)}12(VO)30(H2O)20]36-: a molecular quantum spin
      icosidodecahedron.
AB  - Self-assembly of aqueous solutions of molybdate and vanadate under reducing,
      mildly acidic conditions results in a polyoxomolybdate-based {Mo72V30} cluster
      compound Na8K16(VO)(H2O)5[K10
      subset{(Mo)Mo5O21(H2O)3(SO4)}12(VO)30(H2O)20].150H2O, 1, a quantum spin-based
      Keplerate structure.

PMID- 15968351
TI  - A pH-insensitive, ratiometric chemosensor for citrate using europium
      luminescence.
AB  - A chemoselective sensor for the citrate anion has been devised, based on a new
      europium complex that offers ratiometric analysis of the long-lived emission.

PMID- 15968352
TI  - Rapid and effective labeling of brain tissue using TAT-conjugated CdS:Mn/ZnS
      quantum dots.
AB  - TAT (a cell penetrating peptide)-conjugated CdSratioMn/ZnS quantum dots (Qdots),
      intra-arterially delivered to a rat brain, rapidly (within a few minutes) labeled
      the brain tissue without manipulating the blood-brain-barrier (BBB). Qdot loading
      was sufficiently high that it allowed a gross fluorescent visualization of the
      whole rat brain using a low power hand-held UV lamp. Histological data clearly
      showed that TAT-conjugated Qdots migrated beyond the endothelial cell line and
      reached the brain parenchyma. Qdots without TAT did not label the brain tissue
      confirming the fact that TAT peptide was necessary to overcome the BBB. The
      present study clearly demonstrated the possibility of delivering a large amount
      of Qdot-based imaging agents to the brain tissue.

PMID- 15968353
TI  - New routes to manganese higher-nuclearity topologies: synthesis of the cluster
      [Mn8(mu4-O)4(phpz)8(thf)4].
AB  - Reaction of Mn(ClO4)2.6H2O with 3(5)-methyl-5(3)-(2-hydroxyphenyl)pyrazole
      (H2phpz) affords a highly asymmetric octanuclear manganese(III) cluster resulting
      from the different bridging coordination modes of the ligand H2phpz.

PMID- 15968354
TI  - Hybrid catalysts: the synthesis, structure and ethene polymerisation activity of
      (salicylaldiminato)(pyrrolylaldiminato) titanium complexes.
AB  - The mono(salicylaldiminato) complexes Ti{3-tBu-2-(O)C6H3CH=N(R)}Cl3(THF)(where R
      = C6H5, C6F5) react with the metallated pyrrolylaldiminato ligand, K[2
      (C6H5NCH)C4H3N], to afford the first examples of hybrid salicylaldiminato-ligated
      octahedral titanium complexes; the pre-catalysts give from very high to extremely
      high ethene polymerisation productivities when activated with MAO.

PMID- 15968355
TI  - Programmable DNA translation system using cross-linked DNA mediators.
AB  - The information of template DNA strands was converted into the specific sequences
      in a programmable way by following the mediation of cross-linked DNAs.

PMID- 15968356
TI  - A selective fluorescent ratiometric chemodosimeter for mercury ion.
AB  - A selective fluorescent chemodosimeter for mercury ion based on the mercury
      promoted intramolecular cyclic guanylation of thiourea connected on 1, 8
      naphthalimide is described.

PMID- 15968357
TI  - Concomitant polymorphs of 2,2',6,6'-tetramethyl-4,4'-terphenyldiol: the beta
      quinol network reproduced in a metastable polymorph.
AB  - The striking resemblance of the rhombohedral and monoclinic forms of the title
      molecule to beta- and gamma-quinol provides a crystal engineering approach to new
      polymorphic systems.

PMID- 15968358
TI  - A total synthesis of (+/-)-alpha-cyclopiazonic acid using a cationic cascade.
AB  - The indolic terpene alkaloid alpha-cyclopiazonic acid has been prepared in 11
      steps from indole-4-methanol; the key step is a carbocationic cascade, terminated
      by a 4-nitrosulfonamide group and initiated by benzylic carbocation formation
      directly from the intermediate , which gives the tetracyclic product in 74%
      yield.

PMID- 15968359
TI  - Spontaneous assembly of a nine-vertex lithium framework encapsulating the
      peroxide dianion.
AB  - Investigation of the structure of the lithiated bicyclic guanidine 1,3,4,6,7,8
      hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH) has led to the reproducible
      isolation of compounds containing the 'Li9(hpp)7(O2)' core, in which a peroxide
      dianion has been encapsulated within a mono-capped, cubic array of lithium ions.

PMID- 15968360
TI  - The first hetero-bifunctionalization of the secondary face of beta-cyclodextrin:
      selective and efficient conversion of the A-ring of a 2A,2B-disulfonate to 2A,3A
      epoxymannoside.
AB  - The A-ring of 2(A),2(B)-O,O-di(mesitylenesulfonyl)-beta-cyclodextrin was
      converted to 2(A),3(A)-epoxymannoside without affecting the other sulfonylated
      residue, which affords the first approach to hetero-bifunctionalization at the
      secondary hydroxyl side of cyclodextrins.

PMID- 15968361
TI  - NaOH-catalyzed crossed Claisen condensation between ketene silyl acetals and
      methyl esters.
AB  - We have developed a practical crossed Claisen condensation between ketene silyl
      acetals and methyl esters using catalytic NaOH to obtain alpha-monoalkylated beta
      keto esters and inaccessible alpha,alpha-dialkylated beta-keto esters.

PMID- 15968362
TI  - Efficient solid-phase synthesis of fullero-peptides using Merrifield strategy.
AB  - Boc-protected l-fulleropyrrolidino-glutamic acid was readily prepared and
      employed for the synthesis of fullerene-containing peptides using the solid-phase
      Boc chemistry developed by Merrifield.

PMID- 15968363
TI  - Photoinduced DNA end capping via N3-methyl-5-cyanovinyl-2'-deoxyuridine.
AB  - A modified oligodeoxynucleotide (ODN) containing N(3)-methyl-5-cyanovinyl-2'
      deoxyuridine reacts by photoirradiation at 366 nm with an adenine residue of a
      complementary template ODN to yield an end-capped ODN in 87% yield.

PMID- 15968364
TI  - Stereodifferentiation in the formation and decay of the encounter complex in
      bimolecular electron transfer with photoactivated acceptors.
AB  - Experimental evidence has been obtained for the involvement of encounter
      complexes between both enantiomers of a pi,pi* triplet excited ketone and a
      chiral phenol or indole. Determination of the pre-equilibrium constants (K(EC))
      and the intrinsic decay rate constants (kd) indicates a significant
      stereodifferentiation in both steps of the quenching process.

PMID- 15968365
TI  - Synthesis, characterization and FET properties of novel
      dithiazolylbenzothiadiazole derivatives.
AB  - Dithiazolylbenzothiadiazoles easily obtained have high electron affinity and the
      FET device of a trifluoromethylphenyl derivative exhibited a good n-type
      performance with high electron mobility.

PMID- 15968366
TI  - Efficient charge storage in photoexcited TiO2 nanorod-noble metal nanoparticle
      composite systems.
AB  - Following UV-illumination, TiO2 nanorod-stabilized noble metal (Ag, Au)
      nanoparticles dispersed in deaerated organic mixtures can sustain a higher degree
      of conduction band electron accumulation than that achievable with pristine
      titania.

PMID- 15968367
TI  - Fluorescence probes for thiol-containing amino acids and peptides in aqueous
      solution.
AB  - A new fluorescence probe is described using the "chemosensing ensemble" method.
      The probe shows high selectivity and sensitivity for thiol-containing amino acids
      and peptides, and can detect cysteine and homocysteine from healthy to abnormal
      levels under physiologically-relevant conditions.

PMID- 15968368
TI  - Enhanced relaxation of nanoparticle-bound supercoiled DNA in X-ray radiation.
AB  - A therapeutic methodology was developed based on the large X-ray absorption cross
      section of gold nanoparticles at high photon energies (>81 keV). Experimental
      results showed that the amounts of the relaxed circular supercoiled DNA (scDNA)
      for gold nanoparticle-bound scDNA were more than doubled compared to that for
      free scDNA under otherwise identical radiation conditions.

PMID- 15968369
TI  - A Ru(terpy)(phen)-incorporating ring and its light-induced geometrical changes.
AB  - A Ru(terpy)(phen) motif has been inscribed in a 39-membered ring by
      functionalizing the ligands and subsequently performing a cyclization reaction on
      the complex; by visible light irradiation, a dramatic geometrical changeover of
      the cyclic complex takes place which can be reversed thermally.

PMID- 15968370
TI  - Mild methods to assemble and pattern organic monolayers on hydrogen-terminated
      Si(111).
AB  - Mild methods to assemble well-ordered organic monolayers of olefins on Si(111)
      using 2,2,6,6-tetramethyl-1-piperidinyloxy and to pattern these monolayers on the
      micrometer-size scale using soft lithography are reported.

PMID- 15968371
TI  - Quenching of CdSe quantum dot emission, a new approach for biosensing.
AB  - The emission of CdSe quantum dots linked to the 5'-end of a DNA sequence is
      efficiently quenched by hybridisation with a complementary DNA strand with a gold
      nanoparticle attached at the 3'-end; contact of the quantum dot and gold
      nanoparticle occurs.

PMID- 15968372
TI  - A unique new multiband molecular conductor: [BDTA][Ni(dmit)2]2.
AB  - A new molecular conducting material, [BDTA][Ni(dmit)2]2, with a novel multiband
      electronic structure has been prepared by simple mixing of precursor salts of the
      components.

PMID- 15968373
TI  - A metal nanoparticle-based supramolecular approach for aqueous biphasic
      reactions.
AB  - beta-cyclodextrin immobilized on Pd nanoparticles was successfully employed as an
      efficient phase-transfer catalyst in aqueous biphasic hydrogenation reactions.

PMID- 15968374
TI  - Enantioselective total synthesis of a novel polyketide natural product (+)
      integrasone, an HIV-1 integrase inhibitor.
AB  - Enantioselective total synthesis of the recently isolated, novel polyketide
      natural product (+)-integrasone has been accomplished from the readily available
      Diels-Alder adduct of cyclopentadiene and p-benzoquinone. An enzymatically
      desymmetrized epoxyquinone building block has been elaborated through a series of
      regio- , chemo- and stereocontrolled steps to the final bicyclic framework of the
      natural product.

PMID- 15968375
TI  - Rhodium/diene-catalyzed asymmetric 1,4-addition of arylboronic acids to
      alpha,beta-unsaturated Weinreb amides.
AB  - Rhodium/chiral diene (S,S)- complex has been found to effectively catalyze the
      1,4-addition of arylboronic acids to alpha,beta-unsaturated Weinreb amides,
      furnishing useful beta-chiral Weinreb amides in high enantioselectivity.

PMID- 15968376
TI  - Homoleptic uranium(III) imidodiphosphinochalcogenides including the first
      structurally characterised molecular trivalent actinide-Se bond.
AB  - Preparation of U[N(EPPh2)2]3 (E = S or Se) by treating U[N(SiMe3)2]3 with three
      equivalents of NH(EPPh2)2 is described together with presentation of a hitherto
      unreported molecular crystal structure containing An(III)-Se bonds (An =
      actinide).

PMID- 15968377
TI  - A novel heterogeneous acid-activated clay supported copper catalyst for the
      photobleaching and degradation of textile organic pollutant using photo-Fenton
      like reaction.
AB  - Copper supported on acid-activated bentonite clay was found to be an effective
      catalyst for the photo degradation of Acid Black 1 at pH 3.0-8.0 without
      significant metal leaching.

PMID- 15968378
TI  - Spectroscopic and crystallographic evidence for the N-protonated FeIFeI
      azadithiolate complex related to the active site of Fe-only hydrogenases.
AB  - The complex [{(mu-SCH2)2N(CH2C6H4-2-Br)}Fe2(CO)6] and its N-protonated species,
      as structural models of the Fe-only hydrogenase active site, were identified
      spectroscopically and crystallographically, and their molecular structures show
      the 0.04-0.1 A lengthening of the three N-C bonds and an intramolecular HBr
      contact (2.82 Angstroms) in the crystalline state of the N-protonated species.

PMID- 15968379
TI  - Iodinated molecularly imprinted polymer for room temperature phosphorescence
      optosensing of fluoranthene.
AB  - A novel molecularly imprinted polymer (MIP) of high interest for room temperature
      phosphorescence (RTP) sensing systems is described; the synthesized MIP contains
      iodine as internal heavy atom in the polymeric structure and its applicability
      for RTP sensing of fluoranthene at microg L(-1) levels is demonstrated.

PMID- 15968380
TI  - CD40-CD40L interactions in platelet activation.

PMID- 15968381
TI  - Retinal vein occlusion: a venous complication in an "arterial" patient?

PMID- 15968382
TI  - Nucleic acid aptamers in therapeutic anticoagulation. Technology, development and
      clinical application.
AB  - The evolution of anticoagulant therapy for the prevention and treatment of
      thrombotic disorders has progressed at a relatively modest pace considering the
      scope of the problem and our current understanding of platelet biology,
      coagulation proteases, and vascular science as they apply to protective
      haemostasis and pathologic thrombosis. Recent observations, dedicated to cellular
      based models of coagulation, provide fundamental constructs, mechanistic clarity,
      and potentially unparalleled opportunity for accelerating the development and
      wide-scale clinical use of safe, effective, regulatable and patient-specific
      therapies. The following review introduces a novel domain of anticoagulant
      therapy referred to as aptamers (derived from the Latin aptus - to fit),
      considering their history, development, and potential application in patient care
      arenas.

PMID- 15968383
TI  - Retinal vein occlusion: a form of venous thrombosis or a complication of
      atherosclerosis? A meta-analysis of thrombophilic factors.
AB  - Previous studies have shown an increased risk of retinal vein occlusion (RVO) in
      patients with hypertension, hypercholesterolemia and diabetes mellitus.
      Literature on the association between thrombophilic factors and RVO consists of
      small studies and case reports. The objective was to determine the relationship
      between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed
      were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein
      C and S deficiency, antithrombin deficiency, prothrombin gene mutation,
      anticardiolipin antibodies and lupus anticoagulant. For all currently known
      thrombophilic risk factors odds ratios for RVO were calculated as estimates of
      relative risk. The odds ratios were 8.9 (95% CI 5.7 - 13.7) for
      hyperhomocysteinemia, 3.9 (95% CI 2.3 - 6.7) for anticardiolipin antibodies, 1.2
      (95% CI 0.9 - 1.6) for MTHFR, 1.5 (95% CI 1.0 - 2.2) for factor V Leiden mutation
      and 1.6 (95% CI 0.8 - 3.2) for prothrombin gene mutation. In conclusion,
      regarding thrombophilic risk factors and RVO there is only evidence for an
      association with hyperhomocysteinemia and anticardiolipin antibodies, factors
      that are known as risk factors for venous thrombosis as well as for arterial
      vascular disease. The minor effect of factor V Leiden mutation and the protrombin
      gene mutation (risk factors for venous thrombosis only) suggests that
      atherosclerosis might be an important factor in the development of CRVO.

PMID- 15968384
TI  - Recombinant factor VIIa. An update on its clinical use.
AB  - Recombinant activated factor VII (rFVIIa, NovoSeven) has been successfully used
      to treat bleeding episodes in patients with antibodies against coagulation
      factors VIII and IX. In recent years, rFVIIa has also been employed for the
      management of uncontrolled bleeding in a number of congenital and acquired
      haemostatic abnormalities. Based on a literature search, this review examines the
      current knowledge on therapy with rFVIIa, from the now well-standardized uses to
      the newer and less well-characterised clinical applications.

PMID- 15968385
TI  - Activation of coagulation and inhibition of fibrinolysis in the lung after
      inhalation of lipopolysaccharide by healthy volunteers.
AB  - Pneumonia is frequently associated with changes in coagulation and fibrinolysis
      in the bronchoalveolar space. To determine the effect of lipopolysaccharide (LPS)
      on the hemostatic balance in the human lung, six healthy subjects inhaled
      nebulized LPS or saline in a randomized cross-over study and bronchoalveolar
      lavage fluid was obtained six hours thereafter. LPS induced soluble tissue factor
      and thrombin-antithrombin complexes and inhibited plasminogen activator activity
      in BALF. Additionally plasminogen activator inhibitor type 1 production was
      upregulated after LPS inhalation. LPS also elicited local activation of
      neutrophils (release of elastase, myeloperoxidase and bactericidal/permeability
      increasing protein) and secretion of interleukin (IL)-6 and IL-8. Inhalation of
      LPS by healthy humans reproduces major features of the procoagulant response to
      inflammatory and infectious lung diseases and may be used as a novel model to
      evaluate pathogenetic mechanisms and new interventions.

PMID- 15968386
TI  - Downregulation of vascular endothelial-cadherin expression is associated with an
      increase in vascular tumor growth and hemorrhagic complications.
AB  - The pathogenesis of vascular tumors such as angiosarcomas is poorly understood.
      Cadherin expression inversely correlates with tumor malignancy and the
      endothelial specific VE-cadherin is low or absent in angiosarcomas, suggesting an
      inhibitory role for this protein in tumor progression. In this paper we report
      that PmyT VE-cadherin null (VEC null) endothelial cells form larger vascular
      tumors in nude mice when injected subcutaneously as compared to isogenic VE
      cadherin positive (VEC pos) cells. This effect requires the association of beta
      catenin to VEcadherin, since a VE-cadherin mutant lacking the domain responsible
      for beta-catenin binding (Deltabetacat) cannot rescue the phenotype. In VEC null
      cells beta-catenin is phosphorylated and partly degraded. N-cadherin is increased
      and detected at junctions. VEC null cells also present an altered fibrinolytic
      activity with increases in tPA, uPA, uPAR and a strong reduction in PAI-1, which
      may be correlated to the high incidence of abrupt hemorrhages in VEC null tumors.
      Overall, these data strongly suggest that downregulation of VE-cadherin in
      endothelial tumors may have important consequences for tumor growth and bleeding
      complications.

PMID- 15968387
TI  - Deletion of the 60-loop provides new insights into the substrate and inhibitor
      specificity of thrombin.
AB  - Structural data have indicated that the 60-loop of thrombin with 8-9 insertion
      residues is responsible for the restricted substrate and inhibitor specificity of
      thrombin. However,previous deletion of 3-4 residues of this loop (des-PPW and des
      YPPW) did not widen the specificity of thrombin, but further restricted it. The
      partial deletion of this loop also dramatically impaired the reactivity of
      thrombin with antithrombin (AT), protein C and fibrinogen, implicating a role for
      the productive interaction of the 60-loop with the target macromolecules. To
      further investigate the role of this loop, a mutant of thrombin was expressed in
      mammalian cells in which all 8 residues (Tyr-Pro-Pro-Trp-Asp-Lys-Asn-Phe) of the
      60-loop were deleted (des-60-loop). In contrast to the partially deleted loop
      mutants, it was discovered that the des-60-loop mutant cleaved small synthetic
      substrates, clotted purified fibrinogen, and activated protein C with a near
      normal catalytic efficiency; however, its activity toward cofactors V and VIII
      was impaired approximately 2-4-fold. Direct binding and AT inhibition studies in
      the presence of heparin revealed that the affinity of heparin for interaction
      with exosite-2 of des-60-loop thrombin was impaired, though the reactivity of the
      mutant with AT and other plasma serpins was not impaired, but rather improved
      approximately 2-fold. These results suggest that the 60-loop plays a key role in
      regulating the specificity of thrombin by shielding the active-site pocket, but
      its productive interaction with the target molecules may not be as critical as
      has been speculated in previous reports.

PMID- 15968388
TI  - Molecular design and characterization of recombinant long half-life mutants of
      human tissue factor pathway inhibitor.
AB  - Tissue factor pathway inhibitor (TFPI) is a physiological inhibitor of extrinsic
      pathway of coagulation and has biological functions of anticoagulation and anti
      inflammation. Although TFPI has been proved to be a good therapeutic agent of
      sepsis, inflammatory shock, and DIC, the clinical application and therapeutic
      effects of TFPI are impeded because of its short half-life in vivo. In order to
      prolong the half-life of TFPI, homology modeling and molecule docking were
      performed on a computer workstation principally in protein structural biology and
      binding characteristics between TFPI and its receptor LRP (low-density
      lipoprotein receptor related protein). Two recombinant long half-life human TFPI
      mutants coined TFPI-Mut1 and TFPI-Mut4 were designed and expressed in E.coli. In
      comparison with the wild-type TFPI, TFPI-Mut1 and TFPI-Mut4 presented a few of
      changes in spatial configuration and a decrease in relative Gibbs free energy of
      docking complex by 17.3% and 21.5%, respectively, as indicated by a computer
      simulation. After refolding and purification, anticoagulant activities, anti
      TF/FVIIa and anti-FXa activities of the mutants were found to be the same as
      those of wide-type TFPI. The pharmacokinetics research indicated that alpha phase
      half-life (t1/2 alpha) of TFPI-Mut1 and TFPI-Mut4 were prolonged 1.33-fold and
      1.96-fold respectively, beta phase half-life (t1/2 beta) of TFPI-Mut1 and TFPI
      Mut4 were prolonged 1.62-fold and 4.22-fold respectively. These results suggested
      that TFPI-Mut1 and TFPI-Mut4 maintained the bioactivities of wild-type TFPI,
      prolonged half-life in vivo simultaneously and were expected for better clinical
      value and therapeutic effect.

PMID- 15968389
TI  - Factor VIII efficient and specific non-covalent binding to PEGylated liposomes
      enables prolongation of its circulation time and haemostatic efficacy.
AB  - Haemophilia A is a bleeding disorder caused by the lack of factor VIII (FVIII).
      We report the prolongation of exogenous FVIII circulation time and haemostatic
      efficacy by its formulation with PEGylated liposomes (PEGLip). FVIII binds non
      covalently but with high affinity in a specific mode with the external surface of
      PEGLip neither losing its activity nor its binding to von Willebrand Factor.
      Experiments in haemophilic and non-haemophilic mice indicate that the circulation
      time and clotting efficacy of PEGLip-formulated exogenous FVIII (PEGLip-FVIII)
      are significantly enhanced over those of free FVIII. The data support the
      feasibility of using PEGLip-FVIII to extend the duration of haemostatic efficacy
      in the treatment of haemophilia A.

PMID- 15968390
TI  - Angiotensin II enhances thrombosis development in renovascular hypertensive rats.
AB  - There is an increased number of in vitro evidence that angiotensin II (Ang II)
      may promote thrombosis. However there are no in vivo experiments exploring the
      effect of Ang II on thrombus formation. In the present study we have investigated
      the influence of Ang II on venous thrombosis in renovascular hypertensive rats.
      Furthermore, we examined the role of AT(1) receptor and Ang II metabolites:
      angiotensin III (Ang III) and angiotensin IV (Ang IV) in the mechanisms of Ang II
      action. The contribution of coagulation and fibrinolytic systems in the mode of
      Ang II action was also determined. Venous thrombosis was induced by ligation of
      vena cava. Ang II infused into rats developing venous thrombosis caused dose
      dependent increase in thrombus weight, which was partially reversed by losartan,
      selective AT(1) antagonist. Ang III did not influence the thrombus formation in
      hypertensive rats, while Ang IV caused a marked increase in thrombus weight only
      in one of the used doses. Our study shows that Ang II via AT(1) receptor enhances
      thrombosis development. The prothrombotic effect of Ang II may partially depend
      on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated
      fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is
      partially mediated by one of its metabolites - Ang IV.

PMID- 15968391
TI  - Novel aberrant splicings caused by a splice site mutation (IVS1a+5g>a) in F7
      gene.
AB  - Low FVII coagulant activity (FVII:C 8.2%) and antigen level (FVII:Ag 34.1%) in a
      46-year-old Chinese male led to a diagnosis of coagulation factor VII (FVII)
      deficiency. Compound heterozygous mutations were identified in his F 7 gene:a G
      to A transition in the 5' donor splice site of intron 1a (IVS1a+5g>a) and a T to
      G transition at the nucleotide position 10961 in exon 8, resulting in a His to
      Gln substitution at amino acid residue 348. An analysis of ectopic transcripts of
      F7 in the leukocytes of the patient reveals that the mutation (IVS1a+5g>a) is
      associated with two novel aberrant patterns of splicing. The predominant
      alternative transcript removes exon 2, but retains intron 3, which shifts the
      reading frame and predicts a premature translation termination at the nucleotide
      positions 2-4 in intron 3. The minor alternative transcript skips both exon 2 and
      exon 3 (FVII Delta 2, 3), leading to an in-frame deletion of the propeptide and
      gamma-carboxylated glutamic acid (Gla) domains of mature FVII protein. In vitro
      expression studies of the alternative transcript FVII Delta 2,3 by transient
      transfection of HEK 293 cells with PcDNA 3.1(-) expression vector showed that
      although the mutant protein could be secreted, no pro-coagulation activity was
      detected. The coexistence of the two abnormal transcripts and a heterozygous
      mutation His348Gln, explained the patient's phenotype.

PMID- 15968392
TI  - Characterisation of blood coagulation factor XI T475I.
AB  - PCR-SSCP and DNA sequence analysis of a factor XI (FXI) deficient patient (FXI:C
      39 U/dL; FXI:Ag 27 U/dL) identified a C to T transition in exon 12 of the FXI
      gene (F11 c.1521C>T) that predicts the substitution of Thr475 by Ile (FXI T475I)
      within the serine protease domain of FXI. This mutation destroys a consensus
      sequence for N-linked glycosylation, N473-Y-T475, known to be utilized in vivo.
      The FXIT475I variant was generated by site-directed mutagenesis, together with
      other variants that could help explain the phenotype, and recombinant FXI
      variants were expressed in Chinese hamster ovary cells. FXI:Ag expression was
      analysed by Western blot analysis, ELISA and immunocytochemical staining. Wild
      type FXI:Ag was secreted at high levels, however the mutant (FXI T475I) was
      secreted very poorly. Substitution of Thr475 by Ala, Pro, Lys or Arg (all of
      which abolish the glycosylation consensus sequence) also severely reduced the
      level of secreted FXI:Ag suggesting that glycosylation at Asn473 is required for
      folding or secretion. Concordant with this hypothesis the conservative
      substitution of Thr475 by Ser (which preserves the glycosylation consensus
      sequence) had no effect on FXI secretion. Thr/Ser475 is highly conserved in
      serine protease domains but the glycosylation site (Asn473) is not. Surprisingly,
      substitution of Asn473 by Ala (which removes the N-linked glycosylation site) had
      no effect on the levels of FXI:Ag secreted. In conclusion, although the FXI-T475I
      mutation destroys an N-linked glycosylation consensus sequence, the cause of
      failure to secrete FXI is not the loss of a glycosylation site but rather a
      direct effect of the substitution of this highly conserved residue.

PMID- 15968393
TI  - Elevated factor VII as a risk factor for recurrent fetal loss. Relationship to
      factor VII gene polymorphisms.
AB  - Haemostatic abnormalities can be detected in a portion of the women who have
      recurrent fetal loss. We measured factor VII coagulant activity (FVII:C) in 65
      women with 3 or more fetal losses (recurrent cases), 31 women with one 2nd or 3rd
      trimester loss (late loss cases), and 81 women with only live births (controls).
      FVII:C was greater than 2 standard deviations above the mean for controls in 9
      recurrent cases (13.8%) and 2 controls (2.5%) for an odds ratio of 6.35 (95% CI
      1.32-30.52, p=0.012). In recurrent cases, mean levels were significantly higher
      than controls for FVII:C (p=0.003), FVII antigen (p=0.024), and FVIIa (p=0.001).
      Late loss cases had an odds ratio of 4.23 (95% CI 0.67-26.67, p=0.098) with
      FVII:C, FVII antigen, and FVIIa not significantly different from the controls.
      DNA was examined for the presence of mutations or polymorphisms in the promoter
      region of the FVII gene, using denaturing HPLC. Abnormal patterns were confirmed
      with direct sequencing. A previously reported polymorphism, -402 G>A, was found
      to be present in 11/14 subjects with elevated FVII:C (79%) and 43% of those with
      normal levels (p=0.029). FVII:C, FVII antigen and FVIIa varied significantly with
      genotype; however, genotype frequencies did not differ between controls and
      either case group. No other promoter polymorphisms were identified. This is the
      first report of a significant elevation of FVII in a population with recurrent
      fetal loss. These data suggest the need for further investigation of this
      potential risk factor.

PMID- 15968394
TI  - Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a
      Sardinian population.
AB  - Genetic factors are involved in the individual predisposition to develop ischemic
      stroke (IS). In the present study we tested the role of the Factor VII G10976A
      and -C122T polymorphisms on the susceptibility to develop IS in a genetically
      homogenous and clinically well ascertained case-control study including 294 cases
      (median age 75 years; 176 males/118 females) and 286 controls (median age 73
      years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an
      exploratory analysis with respect to other frequently studied polymorphisms of
      haemostatic factor genes:Factor II G20210A, Factor V G1691A,,Fibrinogen alpha
      chain Thr312Ala, Fibrinogen beta-chain -C148T, Factor XIII G185T, GPIIb/IIIa
      T1565C. Among all the genes tested, FVII -C122T showed a significant, independent
      contribution to IS predisposition both in crude and adjusted analyses (crude OR
      1.52, 95% CI 1.09-2.10, P=0.013; adjusted OR 1.48, 95% CI 1.04-2.09, P=0.028,
      respectively). Haplotype analyses revealed a conserved population structure with
      high linkage disequilibrium between both FVII mutations tested. Blood levels of
      FVII had an inverse relationship with the polymorphism involved. Apart from
      genetic influence, there was a significant role for hypertension (OR=1.7, 95% CI
      1.19-2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% CI 1.38-3.54, P=0.001)
      and atrial fibrillation (OR=1.66, 95% CI 1.06-2.58, P=0.026) on IS occurrence. In
      summary, we describe evidence for a possible direct association of FVII gene
      molecular variants with the occurrence of IS in a genetically homogenous human
      sample.

PMID- 15968395
TI  - Relationship between factor XIII activity, fibrinogen, haemostasis screening
      tests and postoperative bleeding in cardiopulmonary bypass surgery.
AB  - We investigated the relationship between factor XIII, fibrinogen, blood
      coagulation screening tests and postoperative bleeding in 98 patients undergoing
      cardiopulmonary bypass (CPB) surgery. All patients received aprotinin. Blood
      samples were collected preoperatively (T1),after termination of CPB (T2),12 h
      (T3) and 24 h (T4) after surgery to determine FXIII activity, fibrinogen,
      platelet count, prothrombin time (PT), activated partial thromboplastin time
      (APTT) and D-dimers (DD). Laboratory results were correlated with the chest tube
      drainage 24 h after surgery and compared between patients with 24-hour chest tube
      drain volumes in the lower (Group 1) with those in the upper tertile (Group 3).
      Median FXIII and fibrinogen levels dropped by 33.9% and 34.2%, respectively,
      during CPB. No association between FXIII activity and the extent of postoperative
      bleeding was found. However, chest tube bleeding was significantly correlated
      with preoperative and postoperative fibrinogen. This was confirmed by comparing
      Groups 1 and 3. Group 3 patients had significantly lower fibrinogen levels than
      Group 1 at T1 - T4, although most fibrinogen values were within or above the
      reference range (medians, g/l: 3.5 vs. 4.0, p = 0.043 at T1; 2.3 vs. 2.7, p =
      0.015 at T2; 2.9 vs. 3.3, p = 0.008 at T3; 4.2 vs. 5.2, p = 0.002 at T4). There
      was also a significant relationship of platelet count, PT and APTT, as measured
      after CPB (T2), with postoperative chest tube drainage. In conclusion, plasma
      FXIII activity does not influence postoperative bleeding in patients undergoing
      CPB surgery. There is however an inverse association between preoperative or
      postoperative plasma fibrinogen levels and postoperative bleeding. These findings
      indicate a modulation of postoperative bleeding by fibrinogen levels.

PMID- 15968396
TI  - Baseline associations between postmenopausal hormone therapy and inflammatory,
      haemostatic, and lipid biomarkers of coronary heart disease. The Women's Health
      Initiative Observational Study.
AB  - Clinical trials of postmenopausal hormone therapy (PHT) have found an early
      increase in cardiovascular events, and have not demonstrated the reduction in
      coronary heart disease (CHD) predicted from changes in conventional risk factors
      or found in observational studies, suggesting that PHT may increase coronary risk
      through other pathways. We compared baseline levels of C-reactive protein (CRP),
      interleukin-6 (IL-6), sICAM-1, tissue plasminogen activator antigen (tPA
      antigen), D-dimer, homocysteine, triglycerides, total-, HDL- and LDL- cholesterol
      in 304 cases with incident CHD and 304 controls, according to self-reported use
      of PHT. Subjects were selected from the 75,343 participants in the WHI
      Observational Study without baseline cardiovascular disease or cancer. PHT was
      associated with higher CRP, HDL and triglycerides, and lower tPA-antigen and
      homocysteine. CRP was highest in users of unopposed conjugated equine estrogen.
      Levels of IL-6,sICAM-1,D-dimer and total cholesterol did not differ between PHT
      users and non-users. Transdermal estrogen users had low levels of D-dimer and
      CRP. Among users of estrogen plus progestin (EP), CRP, IL-6, tPA-antigen, D
      dimer, total cholesterol and triglycerides were higher in women with incident
      coronary events than controls. Estrogen alone (E) controls shared only the tPA
      antigen association, but had higher HDL and lower LDL than E cases. In non-users
      CRP, tPA-antigen and D-dimer were associated with incident CHD. In summary, risk
      markers differed by PHT category. Some associations differed between women with
      and without incident CHD, especially for EP, where inflammatory and thrombotic
      markers were higher in cases. These associations remain speculative pending
      confirmation in randomized trials.

PMID- 15968397
TI  - High utilization rate of vena cava filters in deep vein thrombosis.
AB  - The objective was to investigate newly diagnosed patients with deep vein
      thrombosis (DVT) who received inferior vena cava filters (IVCFs). A prospective
      registry enrolled 5451 patients from 183 US study sites. In all patients,
      examination by venous duplex ultrasound confirmed the diagnosis of DVT. We
      collected and analyzed data on 781 patients who received an IVCF. The most
      frequently prescribed treatments were low-molecular-weight heparin and
      unfractionated heparin, which were used as a bridge to warfarin in 39% (n=2143)
      and 35% (n=1926) of patients, respectively. Of the total population, 781 (14%)
      (235 outpatients, 546 inpatients) underwent IVCF placement. The most common
      reasons for IVCF placement were contraindication to anticoagulation (n = 271),
      prophylaxis (n = 259), major bleeding related to anticoagulation therapy (n =
      92), and anticoagulation failure (n = 73). Multivariate analysis revealed that
      patients were more likely to undergo IVCF insertion with multiple system organ
      failure (odds ratio [OR], 3.6; 95% CI, 1.48-8.60), previous stroke (OR,3.2;95%
      CI,2.11-4.74), or history of pulmonary embolism (OR,2.4; 95% CI, 1.95-2.91). In
      conclusion, a surprisingly high 14% (781) of patients with confirmed DVT received
      an IVCF. Many of these patients may have warranted less invasive methods of
      venous thromboembolism prophylaxis. Improved physician education regarding
      mechanical and pharmacologic prophylaxis alternatives might reduce the use of
      IVCFs.

PMID- 15968398
TI  - Expression and function of syndecan-4 in human platelets.
AB  - Platelet recruitment crucially depends on amplification systems provided by
      autocrine and paracrine factors such as adenosine diphosphate. In inflammatory
      states, consumption of coagulation proteins, such as antithrombin aggravates the
      procoagulant state. In this study, we report that platelets express syndecan-4,
      an antithrombin-binding cell surface heparan sulphate proteoglycan, whose
      ligation with antithrombin inhibits activated platelet-dependent superoxide anion
      release from neutrophils by the limitation of adenosine diphosphate and adenosine
      triphosphate secretion in activated platelets. Adenosine triphosphate-induced
      platelet aggregation is reduced after treatment of platelets with antithrombin,
      which is reversed by blockade of syndecan-4. We further observed that
      antithrombin limits CD40 ligand expression in adenosine diphosphate-activated
      platelets and inhibits the shedding of syndecan-4 from activated platelets.
      Syndecan-4 appears to be directly involved in regulating platelet aggregation as
      anti-syndecan-4 antibody augments platelet aggregation. We suggest that
      antithrombin might exert beneficial effects in disseminated intravascular
      coagulation by reducing platelet activation, observed as inhibited CD40 ligand
      expression, syndecan-4 shedding, and adenosine diphosphate- and adenosine
      triphosphate-release from activated platelets with subsequent inhibition of
      neutrophil respiratory burst. From these data it is concluded that syndecan-4 may
      play important roles in the regulation of inflammatory effects of platelets.

PMID- 15968399
TI  - Platelet P2Y12 receptors enhance signalling towards procoagulant activity and
      thrombin generation. A study with healthy subjects and patients at thrombotic
      risk.
AB  - Activated platelets participate in arterial thrombosis by forming aggregates and
      potentiating the coagulation through exposure of procoagulant phosphatidylserine.
      The function of the two receptors for ADP, P2Y(1) and P2Y(12), is well
      established in aggregation, but is incompletely understood in the platelet
      procoagulant response. We established that, in PRP from healthy subjects, ADP
      accelerated and potentiated tissue factor induced thrombin generation exclusively
      via stimulation of P2Y(12) and not via P2Y(1) receptors. The P2Y(12) receptors
      also mediated the potentiating effect of PAR-1 stimulation on thrombin
      generation. Furthermore, ADP enhanced in a P2Y(12)-dependent manner the Ca(2+)
      response induced by thrombin, which was either added externally or generated in
      situ. This ADP effect was in part dependent of phosphoinositide 3-kinase and was
      paralleled by increased phosphatidylserine exposure. In PRP from (young) patients
      with either stroke or type-II diabetes, platelet-dependent thrombin generation
      was similarly enhanced byADP or SFLLRN as in healthy subjects. In PRP from stroke
      patients of older age, the P2Y(12)-mediated contribution to thrombin generation
      was variably reduced by two weeks of clopidogrel medication. Remaining P2Y(12)
      activity after medication correlated with remaining P2Y(12)-dependent P-selectin
      exposure, i.e. Ca(2+)-dependent secretion, likely due to incomplete antagonism of
      P2Y(12) receptors. Together, these results indicate that physiological platelet
      agonists amplify phosphatidylserine exposure and subsequent thrombin generation
      by release of ADP and P2Y(12)-receptor stimulation. This P2Y(12) response is
      accomplished by a novel Ca(2+) signalling pathway. It is similarly active in
      platelets from control subjects and patients at thrombotic risk. Finally, the
      thrombogram method is useful for measuring incomplete P2Y(12) inhibition with
      clopidogrel.

PMID- 15968400
TI  - The role of CD40 in CD40L- and antibody-mediated platelet activation.
AB  - Our initial finding that CD40- and CD40 ligand (CD40L)-deficient mice displayed
      prolonged tail bleeding and platelet function analyzer (PFA-100) closure times
      prompted us to further investigate the role of the CD40-CD40L dyad in primary
      hemostasis and platelet function. Recombinant human soluble CD40L (rhsCD40L),
      chemical cross-linking of which suggested a trimeric structure of the protein in
      solution, activated platelets in a CD40-dependent manner as evidenced by
      increased CD62P expression. CD40 monoclonal antibody (mAb) M3, which completely
      blocked rhsCD40L-induced platelet activation, also prolonged PFA-100 closure
      times of normal human blood. In contrast, CD40 mAb G28-5 showed less potential in
      blocking rhsCD40L-induced CD62P expression and did not affect PFA-100 closure
      times. However, when added to the platelets after rhsCD40L, G28-5 significantly
      enhanced the platelet response by causing clustering of, and signaling through,
      FcgammaRII. Similarly, higher order multimeric immune complexes formed at a 1/3
      molar ratio of M90, a CD40L mAb, to rhsCD40L induced strong Fcgamma RII-mediated
      platelet activation when translocated to the platelet surface in a CD40-dependent
      manner, including the induction of morphological shape changes, fibrinogen
      binding, platelet aggregation, dense granule release, microparticle generation
      and monocyte-platelet-conjugate formation. The results suggest that CD40 may play
      a role in primary hemostasis and platelet biology by two independent mechanisms:
      First, by functioning as a primary signaling receptor for CD40L and, second, by
      serving as a docking molecule for CD40L immune complexes. The latter would also
      provide a potential mechanistic explanation for the unexpected high incidence of
      CD40L mAb-associated thrombotic events in recent human and animal studies.

PMID- 15968401
TI  - Antibody profiles for the diagnosis of antiphospholipid syndrome.
AB  - Among the so called 'antiphospholipid antibodies', the presence of Lupus
      Anticoagulant (LA) is associated with thrombosis-related events and defines the
      antiphospholipid syndrome. The role of anti-cardiolipin (aCL) antibodies and anti
      human beta2-glycoprotein I (abeta2GPI) antibodies is less striking. Since the
      problem of standardization for these tests is far from resolved, we evaluated
      whether the combination of results (antiphospholipid laboratory profiles) could
      help to better classify these patients. Over a 6-year period, 618 consecutive
      subjects (55% of whom had previous documented thrombosis-related events) were
      referred to our clinic for Antiphospholipid antibody detection. LA was detected
      according to internationally accepted recommendations. ACL and abeta2GPI
      antibodies were detected by Enzyme-Linked-Immunosorbent Assay (ELISA). Patients'
      records were reviewed for the presence of previous thromboembolic events or
      obstetric complications according to Sapporo's clinical criteria for the
      diagnosis of antiphospholipid syndrome (APS) and each patient underwent a
      physical examination. When individual tests were considered in a multivariate
      analysis which took into account age, gender, the presence of SLE or other
      autoimmune diseases and established risk factors for venous and arterial
      thromboembolism, LA (Odds Ratio 4.4, Confidence Interval 1.5-13.3) and abeta2GPI
      antibodies (Odds Ratio 2.9, Confidence Interval 1.1-7.5) but not aCL antibodies
      (Odds Ratio 1.2, Confidence Interval 0.5-2.7) were found to be independent risk
      factors for thrombosis-related events. When antiphospholipid antibody profiles
      instead of individual test positivity were analyzed in the above mentioned model,
      triple positivity resulted a strong independent risk factor (Odds Ratio 33.3,
      Confidence Interval 7.0-157.6), retaining its significance when the association
      with venous or arterial thromboembolism was considered. Double positivity with
      negative LA was close to significance for thrombosis-related events (Odds Ratio
      2.2, Confidence Interval 1.0-5.2, p=0.056) and highly significant risk factor for
      obstetric complications (Odds Ratio 10.8, Confidence Interval 2.9-40.8). Other
      combinations did not reach statistical significance. The mean level of IgG
      abeta2GPI antibodies was statistically higher in triple positive profile and
      might account for positive LA. As compared to a single test, the analysis of a
      complete antiphospholipid antibody profile can better determine patients at risk.

PMID- 15968402
TI  - Relationship between peripheral arterial occlusive disease (PAOD) and chronic
      Chlamydophila (Chlamydia) pneumoniae infection. A meta-analysis.
AB  - We carried out a meta-analysis of observational case-control studies published
      before May 2004 to assess the degree of association between Chlamydophila
      pneumoniae (Cp) infection and PAOD. A search of the Medline database was
      performed using atherosclerosis and "Chlamyd* pneumoniae" as keywords. Strict
      criteria were applied for the selection of case studies, which had to be studies
      of Cp seroprevalence or of Cp detection in patients versus controls. Forty-three
      published studies that met these criteria were selected. An association between
      PAOD and Cp was revealed by immunohistochemical analysis (OR=15.4, 95%CI=5.0
      46.9) and nested PCR studies of arterial biopsies (OR=4.3, 95%CI=1.8-10), by PCR
      study of non-arterial samples (OR=2.9, 95%CI=1.2-7.0), by other direct-detection
      tests (OR=16.7, 95%CI=7.0-39.8), and by ELISA and MIF tests to detect high IgG
      (OR=2, 95%CI=1.1-3.5 and OR=1.7, 95%CI=1.0-2.9, respectively) and IgA (OR=1.9,
      95%CI=1.1-3.4 and OR=1.5, 95%CI=1.1-2.0, respectively) titers. No significant
      association was found in simple PCR studies of arterial biopsies, MIF tests to
      detect low IgG titers or IgM, or ELISA studies to detect IgM. According to this
      review, the association between Cp infection and PAOD depends on the analytical
      method adopted. Establishing a relationship between Cp and PAOD will require a
      case-control study with an adequate number of cases and samples that uses a
      combination of direct and indirect techniques to identify the presence of the
      bacterium in different types of sample from the same subjects, correlating the
      results with the activity of the disease.

PMID- 15968403
TI  - Endothelial nitric oxide synthase plays a minor role in inhibition of arterial
      thrombus formation.
AB  - Endothelial NO synthase (eNOS) expressed in the vascular endothelium or formed
      within platelets was postulated to inhibit platelet activation and aggregation.
      We have assessed the role of eNOS in platelet aggregation in vitro and in vivo by
      comparison of WT and eNOS-/- mice. Aggregometer studies revealed that collagen
      over a concentration range of 0.36-10 microg aggregated WT and eNOS-/- platelets
      to the same extent (10 microg: WT 86.7+/-4.7%, eNOS-/- 91+/-12%, n=6). Collagen
      treatment did not result in a significant increase in cGMP formation and VASP
      phosphorylation. Thrombin-induced P-selectin surface expression was unchanged in
      eNOS-/-platelets. In line with these findings no eNOS protein was detectable
      within the platelets of WT mice. In vivo, bleeding time after tail tip resection
      tended to be shorter in eNOS/- mice (WT: 116+/-35 s; eNOS-/- 109+/-37 s, n.s).
      Similarly, time to occlusion of the A.carotis after focal induction of thrombosis
      was 501+/-76 s (WT) and 457+/-95 s (eNOS-/-) (n.s.). These data demonstrate that
      eNOS-deficiency minimally affects platelet aggregation and is not associated with
      accelerated arterial thrombosis in vivo. Thus, in the mouse endothelial NO
      synthase does not play a major role in the autocrine modulation of platelet
      function and in thrombosis of conduit vessels in vivo.

PMID- 15968404
TI  - Thrombin activates the p21-activated kinase in pulmonary artery smooth muscle
      cells. Role in tissue factor expression.
AB  - The p21-activated serine/threonine kinases (PAK) play an important role in a
      variety of cellular functions. However, their role in the smooth muscle response
      to thrombin, which is activated upon vascular injury and promotes vascular
      remodelling processes, is not resolved. Here we investigated the role of PAK in
      thrombin signalling and regulation of tissue factor (TF), the activator of the
      extrinsic coagulation cascade, in pulmonary artery smooth muscle cells (PASMC),
      the main cell type responsible for vascular remodelling in pulmonary
      hypertension. PAK was rapidly phosphorylated in response to thrombin. Thrombin
      and active PAKT423E phosphorylated p38 MAP kinase (p38MAPK), ERK1/2,
      phosphatidylinositol-dependent kinase-1 (PDK1) and protein kinase B/Akt (PKB)
      whereas kinase-deficient PAK1 prevented activation of these kinases by thrombin.
      In addition, kinase- deficient MKK3 inhibited activation of PDK1 and PKB by
      thrombin. Further, thrombin and active PAK1 induced TF expression and promoter
      activity while kinase-deficient PAK1 diminished thrombin-induced TF upregulation.
      Moreover, kinase-deficient MKK3, PDK1 and PKB inhibited thrombin- and PAK
      dependent TF expression and promoter activity. Together these findings show that
      PAK is a critical element of thrombin signalling in PASMC which is involved in
      the regulation of TF expression by sequentially activating MKK3/p38MAPK, PDK1 and
      PKB. Thus, PAK may play an important role in promoting vascular remodelling
      processes in pulmonary hypertension.

PMID- 15968405
TI  - Transcriptional regulation of plasminogen activator inhibitor-1 expression by
      insulin-like growth factor-1 via MAP kinases and hypoxia-inducible factor-1 in
      HepG2 cells.
AB  - Insulin-like growth factor 1 (IGF-1) and plasminogen activator inhibitor-1 (PAI
      1) appear to play a crucial role in a number of processes associated with growth
      and tissue remodelling. IGF-1 was shown to enhance PAI-1 expression in primary
      hepatocytes and HepG2 hepatoma cells, but the molecular mechanisms underlying
      this effect have not been fully elucidated. In this study, we investigated the
      transcriptional mechanism and the signaling pathway by which IGF-1 mediates
      induction of PAI-1 expression in HepG2 cells. By using human PAI-1 promoter
      reporter gene assays we found that mutation of the hypoxia responsive element
      (HRE), which could bind hypoxia-inducible factor-1 (HIF-1), nearly abolished the
      induction by IGF-1. We found that IGF-1-induced up-regulation of PAI-1 expression
      was associated with activation of HIF-1 alpha. Furthermore,IGF-1 enhanced HIF
      1alpha protein levels and HIF-1 DNA-binding to each HRE,E4 and E5 as shown by
      EMSA. Mutation of the E-boxes, E4 and E5, did not affect the IGF-1-dependent
      induction of PAI-1 promoter constructs under normoxia but abolished the effect of
      IGF-1 under hypoxia. Inhibition of either the PI3K by LY294002 or ERK1/2 by U0126
      reduced HIF-1alpha protein levels while both inhibitors together completely
      abolished the IGF-1 effect on HIF-1alpha. Remarkably, transfection of HepG2 cells
      with vectors expressing a dominant-negative PDK1 or the PKB inhibitor, TRB3, did
      not influence while dominant-negative Raf inhibited the IGF-1 effect on HIF
      1alpha. Thus, IGF-1 activates human PAI-1 gene expression through activation of
      the PI3-kinase and ERK1/2 via HIF-1alpha.

PMID- 15968406
TI  - Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate
      in extended duration therapy for venous thromboembolism in cancer patients.
AB  - Many patients with venous thromboembolism are being treated with low molecular
      weight heparin for extended periods of time. It is not certain if it is necessary
      to assess anti-Xa levels for extended treatment periods. This study is a
      prospective assessment of anti-Xa levels in patients on long-term therapy for
      acute venous thromboembolism who have active cancer. Consecutive consenting
      patients from one center in a multicenter trial that compared 6 months of low
      molecular weight heparin with oral anticoagulant therapy were treated with
      therapeutic doses of dalteparin (200 IU per kilogram) subcutaneously daily. Anti
      Xa levels were assessed at the end of weeks 1 and 4,4-6 hours after injection of
      dalteparin. Patients were followed for bleeding and recurrent venous
      thromboembolism. There were 24 patients who had anti-Xa levels measured at weeks
      1 and 4. Two other patients had week 1 measurements performed but died before the
      week 4 sample was collected due to their underlying cancer. The mean anti-Xa
      levels at weeks 1 and 4 were 1.11 and 1.03 anti-Xa units/ml respectively
      (P=0.13). These results suggest that for patients with active cancer receiving
      extended duration therapy with low molecular weight heparin (dalteparin) there is
      no accumulation of anti-Xa effect over the first month of therapy. Monitoring of
      anti-Xa levels in this situation is usually not required.

PMID- 15968407
TI  - Long-term stability and reproducibility of CoaguChek test strips.
AB  - Whole-blood point-of-care testing prothrombin time monitors are being used on an
      increasing scale for the monitoring of oral anticoagulant therapy. These monitors
      are used with disposable test strips containing tissue factor reagent. The
      purpose of the present study was to assess the stability of different CoaguChek-S
      strip lots for a period of one year. Ten strip lots introduced successively in
      the Netherlands were obtained from the manufacturer's representative and stored
      at 4-8 degrees C. Six deep-frozen pooled plasmas were analyzed for the
      prothrombin time and INR with the strips at six or seven occasions spread over
      one year. The test plasmas were recalcified immediately before application to the
      CoaguChek-S system. Regression analysis was performed on the clotting times
      obtained with each plasma. In the majority of cases (i.e.95%), no significant
      change was observed at the 5% significance level. A significant change was
      observed in only 3 cases. In addition, a ranking statistic was used as test of a
      monotonic relationship in the two-way analysis of variance. The results of the
      ranking statistic were not significant for any strip lot, indicating that the
      test strips were stable under these storage conditions. The reproducibility of
      INR measured with the CoaguChek-S was assessed. The mean within-run coefficient
      of variation (CV) of INR ranged from 2.58% to 3.36% (CV). The between-lot
      variation of the mean INR ranged from 3.2 to 4.5 % (CV). The over-all variation
      of single INR measurements, i.e. including between-lot and within-lot, ranged
      from 5.0 to 6.0 % (CV).

PMID- 15968408
TI  - Double heterozygosity for Factor V Leiden and Factor V Cambridge mutations
      associated with low levels of activated protein C resistance in a Spanish
      thrombophilic family.

PMID- 15968409
TI  - Novel gamma230 Asn-->Asp substitution in fibrinogen Middlemore associated
      hypofibrinogenaemia.

PMID- 15968410
TI  - Selection of both normal and bleeding patients is indicated before desmopressin
      administration.

PMID- 15968411
TI  - Inihibition of cytokine response by methylprednisolone attenuates antithrombin
      reduction following hepatic resection.

PMID- 15968412
TI  - Green tea catechins containing a galloyl group in the 3' position inhibit tissue
      factor-induced thrombin generation.

PMID- 15968413
TI  - Myocardial perfusion/metabolism mismatch and ventricular arrhythmias in the
      chronic post infarction state.
AB  - AIM: Ventricular arrhythmias have been shown to originate in the myocardial peri
      infarct region due to irregular heterotopic conduction. Hypoperfused but viable
      myocardium is often localised in those areas and may be involved in the
      pathogenesis of arrhythmias. We tested the hypothesis that these myocardial
      perfusion/metabolism mismatches (MM) are significantly associated with
      ventricular arrhythmias in the chronic post infarction state. PATIENTS, METHODS:
      47 post infarction patients were included in the study. 33 suffered from
      ventricular arrhythmia whereas 14 did not. All patients underwent (99m)Tc
      tetrofosmin SPECT and (18)F-FDG PET. A region-of-interest(ROI)-analysis was used
      to assess viable myocardium based on predefined MM-criteria. Univariate analyses
      as well as a logistic regression model for the multivariate analysis were carried
      out. RESULTS: 94% of the arrhythmic patients displayed at least one MM-segment as
      compared to 64% of the non-arrhythmic patients. MM-segments and arrhythmia showed
      a statistically significant relation (p = 0.018). The logistic regression model
      predicted the occurrence or absence of arrhythmia in 85% of all cases.
      Multivariate analysis gave consistent results, after adjusting for symptomatic
      chronic heart failure (CHF), aneurysms and age. CONCLUSION: Our results support
      the hypothesis that hypoperfused but viable myocardium represents an
      arrhythmogenic substrate and is a relevant risk factor for developing ventricular
      arrhythmias following myocardial infarction. Therefore, the detection of MM
      segments allows the identification of patients with a higher risk for future
      cardiac events.

PMID- 15968414
TI  - Direct injection of (188)Re-microspheres in the treatment of hepatocellular
      carcinoma: compared with traditional percutaneous ethanol injection: an animal
      study.
AB  - The AIM of this study was to compare the therapeutic efficacies of direct
      intratumoural injection of (188)Re microspheres (DIRM) and direct intratumoural
      injection of ethanol (DIE) in rabbits bearing liver tumours. MATERIALS AND
      METHODS: Fifteen rabbits bearing liver tumours were divided into three groups:
      group 1 received DIE, group 2 received DIRM, and group 3 (control) received
      saline. Tumour size was measured by liver sonography before injection, as well as
      2, 4, 8, and 12 weeks after injection. Survival time was calculated from the day
      of treatment to three months after treatment by Kaplan-Meier survival analysis.
      RESULTS: The mean survival time was 68 +/- 9.8 days for the rabbits in the DIRM
      group, 55.8 +/- 11.8 days for the DIE group, and 38.8 +/- 6.2 days for the
      control group. CONCLUSION: The rabbits survived longer in the DIRM group than in
      the DIE group although there is no statistical significance. We believe the DIRM
      method has a good potential to be an alternative to DIE for the treatment of
      liver tumours.

PMID- 15968415
TI  - Is normal gastric emptying a predictor of normal gastric function?
AB  - AIM: Impaired gastric emptying is common in many disorders. Assuming that gastric
      disorders primarily affect gastric peristalsis, which secondarily results in
      impaired emptying, the aim of our study was to evaluate whether quantitative
      analysis of gastric peristalsis might be a more sensitive parameter than gastric
      emptying to demonstrate functional gastric impairment. PATIENTS, METHODS: Gastric
      emptying was determined scintigraphically in 141 adult (age: 18-78 years)
      patients (long-term Type 1 diabetes mellitus, 82 cases; systemic sclerosis, 31
      cases; atrophic gastritis, 28 cases) and 20 healthy age-matched controls after
      ingestion of a semiliquid test meal. In addition, gastric peristalsis was
      evaluated by Fourier analysis of condensed images. RESULTS: Compared to the
      control persons emptying was delayed in 75/141 patients, regular in 63/141
      patients, and accelerated in 3/141 patients. As expected, 81% of patients with
      delayed emptying presented with diminished gastric contraction amplitudes.
      However, independent of the aetiology of the underlying disorder, 40/63 patients
      with regular emptying also exhibited reduced peristalsis. CONCLUSION: Normal
      gastric emptying does not predict normal gastric function. This assumption is
      supported by the presence of reduced amplitudes in subgroups of patients with
      various disorders and normal emptying. Our results suggest that the amplitude of
      gastric contractions may represent a more sensitive parameter for the detection
      of gastric dysfunction than does gastric emptying.

PMID- 15968416
TI  - Expression of the sodium iodide symporter in differentiated thyroid cancer:
      clinical evidence.
AB  - AIM: Molecular analysis of the expression of the sodium iodide symporter (NIS) in
      32 patients with differentiated thyroid cancer (DTC) and correlation with
      scintigraphic findings ((131)I,(123)I) in 19 (59.4%) of them. PATIENTS, METHODS:
      NIS expression of 27 primary tumours, 13 lymphnodes and 18 distant metastases was
      determined by immunostaining using a murine monoclonal anti-NIS-antibody. NIS
      expression and radionuclide uptake of metastases were analysed by a
      semiquantitative visual score. Patients were divided into two subgroups: Group 1
      (n = 8 patients): indirect correlation of radioiodine uptake (RIU) of subsequent
      metastases with NIS expression of 7 primary tumours and 3 metastases; Group 2
      (n=11 patients): direct correlation of radionuclide uptake with NIS expression of
      19 metastases which were excised after imaging. RESULTS: 49 of 58 specimens
      (84.5%) were NIS-positive. A preserved NIS-expression was found in 12 primary
      tumours and 8 of 10 (80%) synchrone and 6 of 7 (85.7%) metachrone metastases.
      Group 1 revealed a 100% positive predictive value (PPV) of a preserved NIS
      expression in the primary tumour regarding radioiodine uptake in metastases while
      a lack of NIS expression in the primary tumor did not reliable predict a loss of
      the metastases' ability to concentrate radioiodine. In group 2, only 11 of 19
      (57.9%) specimens showed a concordant NIS expression and RIU whereas in the
      remaining 8 cases without visible RIU NIS expression was still present.
      CONCLUSIONS: NIS expression of the primary tumour and metastases in DTC is
      usually well preserved. We found a positive correlation between NIS expression of
      the primary and metastatic tissue but could not identify such well correspondence
      between NIS expression and the RIU of subsequent metastases.

PMID- 15968417
TI  - [beta-Radiation exposure with (188)Re-labelled pharmaceuticals].
AB  - AIM: The number of therapies with radiopharmaceuticals labelled with (188)Re is
      increasing requiring the documentation of the beta radiation exposure Hp(0.07) of
      the staff at all working and production sites and during the application and
      follow-up of the patient according to the new German Radiation Protection Law
      (StrlSchV). However, data for beta-radiation exposure are rare. Therefore, we
      determined the personal dose Hp(0.07) of the skin of the hands handling (188)Re
      radiopharmaceuticals to identify steps of high radiation exposure and to optimize
      working conditions. METHOD: Thermoluminescence dosimeters (TLD 100) were fixed to
      the fingertips of the radiochemist, the physician and the nurse and compared to
      official ring dosimeters. In addition, to monitor radiation exposure continuously
      readable electronic beta- and gamma dosimeters EPD (Siemens) were used. At eight
      days in which therapies were performed these readings were evaluated. RESULTS:
      Considering one therapy with a (188)Re-labelled radiopharmaceutical the middle
      finger of the radiochemist (production) and the physician (application) showed a
      radiation burden of 894 and 664 muSv/GBq, respectively. The cumulative dose of
      the fingertips after eight days of therapy was 249 and 110 mSv for the
      radiochemist and physician, respectively. A cumulative finger dose after eight
      days of therapy of 17 and 38 muSv/GBq was found for physician and nurse leading
      to a Hp(0.07) of 3 and 6 mSv, respectively. Preparing the radiopharmaceutical
      labelled with 20GBq of (188)Re the reading of the personal electronic dosimeter
      of the radiochemist showed a gamma-dose rate Hp(10) of 55 muSv/h and a beta-dose
      rate Hp(0.07) of 663 muSv/h which are obviously not representative for the true
      radiation dose to the skin of the fingertips. CONCLUSION: During therapy with
      (188)Re-labelled radiopharmaceuticals the true radiation dose to the skin of the
      finger tips exceeds by far the readings of the official ring dosimeters as well
      as the continuously readable beta- and gamma dosimeters. This means a risk in
      exceeding the radiation limit of 500 mSv/a given in the German Radiation
      Protection Law ( section sign55 StrSchV) primarily in the working field of the
      radiochemist and the administering physician.

PMID- 15968418
TI  - The influence of filtered back-projection and iterative reconstruction on partial
      volume correction in PET.
AB  - AIM: We assess the influence of the reconstruction algorithms [OS-EM for the
      iterative one vs. a filtered back-projection in Fourier space (DiFT)] on partial
      volume correction in PET employing a fully 3D 3-compartment MR based PV
      correction algorithm. The gray matter voxels in the PET image -- after removal of
      the white matter and cerebrospinal fluid contribution -- are corrected voxel-by
      voxel using the image resolution. MATERIAL, METHODS: Phantom measurements and one
      healthy human brain FDG study were carried out. For the OSEM reconstruction, a
      combination of iteration steps and subset numbers (It/Sub) was used, whereby in
      case of no-convergence the image resolution had to be fitted. The RESULTS from
      the DiFT reconstruction were equivalent to those obtained from the OSEM
      reconstruction with 10/32 combination for objects with widespread activity
      concentration. For the sphere phantom, the mean recovery based on the actual
      values achieved 99.2% +/- 1.8 for all spheres and all reconstruction modes and
      It/sub combinations (except for 2/8). In case of the Hoffman 3D brain phantom the
      mean recovery of the cortical regions was 101% +/- 1.2 (the increase based on the
      uncorrected values: 35.5% +/- 1.5), while the subcortical regions reached a mean
      recovery of 80% with an increase of 43.9% +/- 2.5. For the human data, an
      increase of the metabolized values of several cortical regions ranged between 42%
      and 48% independent from the reconstruction mode. CONCLUSIONS: Our data show that
      the 3-compartment fully 3-D MR based PV-correction is sensitive to the choice of
      reconstruction algorithms and to the parameter choice. They indicate that despite
      improved spatial resolution, the use of the iterative reconstruction algorithm
      for PV-correction results in similar recovery factors when compared to a
      correction using DiFT reconstruction, insofar the image resolution values are
      fitted at the It/Sub combinations.

PMID- 15968419
TI  - [Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic
      syndrome: conceptual chances].
AB  - The prognosis of patients with acute myeloid leukaemia (AML) has improved
      considerably by introduction of aggressive consolidation chemotherapy and
      haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of
      patients with AML achieve long-term disease-free survival after SCT. The most
      common cause of treatment failure is relapse. Additionally, mortality rates are
      significantly increased by therapy-related causes such as toxicity of
      chemotherapy and complications of SCT. Including radioimmunotherapies in the
      treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of
      a pronounced antileukaemic effect for the reduction of relapse rates on the one
      hand. On the other hand, no increase of acute toxicity and later complications
      should be induced. These effects are important for the primary reduction of
      tumour cells as well as for the myeloablative conditioning before SCT. This paper
      provides a systematic and critical review of the currently used radionuclides and
      immunoconjugates for the treatment of AML and MDS and summarizes the literature
      on primary tumour cell reductive radioimmunotherapies on the one hand and
      conditioning radioimmunotherapies before SCT on the other hand.

PMID- 15968420
TI  - Optical detection of single molecules in living cells.
AB  - Single molecule detection is a technology of studying biomolecules with high
      spatial and temporal resolution. By exploiting recent technical advances, we are
      able to observe, detect, even manipulate individual molecules and study their
      conformational changes and dynamic behaviors. New information can be obtained
      from the single molecule research, which is otherwise hidden or averaged out. In
      recent years, the development of single molecule detection techniques has opened
      up a new era of life science. In this review, we introduce the advances of the
      techniques for detecting single molecules in cell biology and review the
      development of single molecule detection in living cells.

PMID- 15968421
TI  - Correlations between edema and the immediate and prolonged painful consequences
      of inflammation: therapeutic implications?
AB  - The precise relationship between the degree of pain and the degree of
      inflammation in the individual remains debated. A quantitative analysis
      simultaneously applied to the immediate and prolonged painful consequences of
      inflammation has not yet been done. Thus, the correlations between edema,
      nociception and hypersensitivity following an inflammatory insult were assessed
      in rodents. To better understand the therapeutic value of modifying specific
      aspects of inflammation, the effects of an anti-inflammatory drug were compared
      to the results. Inbred strains of mice and outbred rats received an intraplantar
      injection of honeybee venom and the between-group and within-group correlations
      were calculated for spontaneous nociceptive measures, thermal and mechanical
      hypersensitivity, and edema and temperature. The effect of indomethacin on the
      pain and inflammation measures was examined. Edema correlated with spontaneous
      flinching, licking and lifting of the injected paw (P< or =0.003), and not with
      thermal or mechanical hypersensitivity. Indomethacin affected edema and
      spontaneous nociception dose-dependently, and affected hypersensitivity only at
      the highest dose tested (P< 0.05). These results suggest that edema may
      contribute only to immediate spontaneous nociceptive responses to an inflammatory
      insult, and not to the more clinically relevant prolonged hypersensitivity. This
      analysis represents a method for determining which inflammatory processes are the
      most promising therapeutic targets against the multiple painful consequences of
      inflammation.

PMID- 15968422
TI  - Neuroprotective effect of lysophosphatidic acid on AbetaP31-35-induced apoptosis
      in cultured cortical neurons.
AB  - It has been reported that lysophosphatidic acid (LPA) at its lower concentrations
      prevents apoptosis induced by serum-deprivation in cultured cortical neurons when
      LPA is added into the cultural medium with serum withdrawal. The present study
      was designed to investigate whether LPA could also block the apoptosis induced by
      beta-amyloid peptide fragment 31-35 (AbetaP31-35) in cultured cortical neurons by
      using techniques of DNA fragmentation electrophoresis, HO33342 staining, and
      TUNEL examinations. The results showed that pretreatment of LPA suppressed the
      AbetaP31-35-induced apoptosis only when LPA was applied to the cultured neurons
      with lower concentrations (1-10 micromol/L) and especially, with a preceding time
      of 12-24 h before the AbetaP31-35 exposure. These facts imply that LPA also acts
      as a neuroprotective factor against AbetaP31-35-induced apoptosis, though the
      mechanism underlying the protective action in this case may be more complex than
      that involved in the serum deprivation-induced apoptosis.

PMID- 15968424
TI  - [Effect of IP3 on BK channels of porcine coronary artery smooth muscle cells].
AB  - D-myo-inositol 1,4,5-trisphosphate (IP(3)) plays an important role in signal
      transduction. It releases Ca(2+) from intracellular sites, which activates the
      Ca(2+)-dependent channels such as large-conductance Ca(2+)-activated potassium
      channels (BK channels). The present study was therefore designed to determine if
      the activity of BK channels in porcine coronary artery smooth muscle cells was
      increased by IP(3). Using the inside-out patch-clamp technique, the activity of
      single BK channels was recorded in porcine coronary artery smooth muscle cells.
      In excised inside-out membrane patches, IP(3) (10-50 micromol/L) enhanced the
      open probability (Po) of BK channels in a dose-dependent manner in the
      intracellular side of inside-out patches and its effect was almost completely
      abolished by washout. The open-state probability of the BK channels increased
      from a control level of 0.0402+/-0.0152 to 0.1365+/-0.0212 (20 micromol/L IP(3))
      and 0.1865+/-0.0175 (30 micromol/L IP(3)). IP(3) decreased the mean close time
      markedly, but had no effect on the amplitude of BK channels. The activation of
      IP(3) on BK channels did not decline. The metabolite of IP(3) had no obvious
      effect on BK channels. This study provides evidence that IP(3) activates BK
      channels in porcine coronary artery smooth muscle cells in a dose-dependence
      manner.

PMID- 15968423
TI  - [Serum response factor participates in RhoA-induced endothelial cell F-actin
      rearrangements].
AB  - RhoA is one of the main members of RhoGTPase family involved in cell morphology,
      smooth muscle contraction, cytoskeletal microfilaments and stress fiber
      formation. It has been demonstrated that RhoA modulates endothelial cell
      permeability by its effect on F-actin rearrangement, but the molecular mechanism
      of rearrangement of actin cytoskeleton remains unclear. Recent studies prove that
      RhoA/Rho kinase regulates smooth muscle specific actin dynamics by activating
      serum response factor (SRF)-dependent transcription. To further investigate the
      molecular mechanism of the rearrangement of vascular endothelial cell actin
      cytoskeleton, we explored the relationship between the activation of SRF and F
      actin rearrangement induced by RhoA in human umbilical vein endothelial cells
      (HUVECs). HUVECs were infected with the constitutively active forms of RhoA
      (Q63LRhoA) or the dominant negative forms of RhoA(T19NRhoA) using retrovirus
      vector pLNCX-Q63LRhoA or pLNCX-T19NRhoA, the positive clone was obtained by G418
      selection. The expression and distribution of SRF in normal and infected cells
      were evaluated by immunohistochemistry and Western blot in complete medium and in
      serum-free medium. The effect of F-actin polymerization was detected by Rhodamine
      Phalloidine staining. Infection of PLNCX-Q63LRhoA induced F-actin rearrangement
      and stress fiber formation in HUVECs, as well as enhanced the expression of SRF
      in the nuclei. In contrast, the cells infected with T19NRhoA showed no distinct
      changes. With serum deprivation, the expression of SRF increased obviously in
      both normal and infected HUVECs, but the subcellular localization of SRF was
      evidently different. In HUVECs, the localization of SRF was in the nuclei after 3
      d with serum deprivation, but it was redistributed outside the nuclei after 5 d
      with serum deprivation. In cells infected with Q63LRhoA, the immunolocalization
      of SRF was always in the nuclei compared with HUVECs infected with T19NRhoA,
      which was almost always localized in the cytoplasm. In HUVECs, the rearrangement
      of F-actin and formation of stress fiber increased after 3 d with serum
      deprivation, but appeared decreased and unpolymerized after 5 d with serum
      deprivation. The polymerization of F-actin and the formation of stress fiber in
      HUVECs infected with Q63LRhoA kept during the period of serum-free culture,
      whereas the rearrangement of F-actin in cells infected with T19NRhoA was not
      found. These results suggest that RhoA influences endothelial F-actin
      rearrangement in part by regulating the expression and subcellular localization
      of SRF.

PMID- 15968425
TI  - [Dephosphorelation of Bad and upregulation of Bcl-2 in hippocampus of rats
      following limbic seizure induced by kainic acid injection into amygdaloid
      nucleus].
AB  - The purpose of the present study was to explore the seizure-induced changes in
      Bad (Bcl-2-associated death protein), 14-3-3, phosphoBad, Bcl-2 and Bcl-XL
      expression in the rat model of focal limbic seizure. Unilateral intra-amygdaloid
      injection of kainic acid (KA) was made to induce seizure. Electroencephalogram
      (EEG) and regional cerebral flow (r-CBF) were monitored continuously. Diazepam
      (30 mg/kg) was administered to terminate the seizure. The apoptotic and surviving
      neurons in the hippocampus were observed by terminal deoxynucleotidyl
      transferrase-mediated dUTP nick end labeling (TUNEL) and cresyl violet staining,
      the expression of Bad, 14-3-3, phosphoBad, Bcl-2 and Bcl-XL were detected with
      immunofluorescence, Western blot and immunoprecipitation. The results showed that
      TUNEL-positive neurons appeared at 8 h and reached maximum at 24 h following
      seizure cessation within the ipsilateral CA3 subfield of the hippocampus. Seizure
      induced the dephosphorylation of Bad and the dissociation of Bad from its
      chaperone protein 14-3-3 and subsequent dimerization of Bad with Bcl-XL. The
      expression of phosphoBad decreased and Bcl-2 increased. There was little change
      in r-CBF after the seizure. These results suggest that seizure leads to a
      dephosphorylation of Bad and an upregulation of Bcl-2. Dephosphorylation of Bad
      may be injurious while the upregulation of Bcl-2 may be protective to the brain
      damage induced by seizures, but not related with r-CBF.

PMID- 15968426
TI  - [Melatonin inhibits the proliferation of pituitary prolactin-secreting tumor by
      suppressing the enhancer elements mutation of PRL gene in the rat].
AB  - In order to investigate the molecular mechanisms of the inhibition of the
      proliferation of 17-beta-estradiol (E(2))-induced pituitary prolactin-secreting
      tumor (prolactinoma) by melatonin (MLT) in the rat, we examined the inhibitory
      effects of MLT on the proliferation of E(2)-induced prolactinoma of the rat and
      the suppressing effects of MLT on the enhancer elements mutation of PRL gene in
      vivo and in vitro. The results showed that the weights of prolactinomas in MLT
      groups, in which 0.25 mg or 0.50 mg per day per rat of MLT was administered
      subcutaneously at 18:00, were decreased significantly. Out of the dosage of MLT,
      such as 0.05, 1.00 mg and 2.00 mg per day per rat, the antitumor action of MLT is
      less or disappointing. Polymerase chain reaction (PCR) and DNA sequencing showed
      five mutations in the enhancer elements of PRL gene in prolactinoma, such as 
      1885 point mutation (C --> G), -1857 - -1855 substitution (ACA --> G), -1792 - 
      1791 insertion G, -1383 - -1382 insertion (GGTGTGTG), -1265 - -1250 deletion
      (GTGTGTGTGTGTGTGT). Excluding of -1885 point mutation (C --> G), the mutation in
      the prolactinoma treated with 0.25 mg per day per rat MLT was decreased, such as 
      1792 - -1791 without insertion of G, -1856 - -1855 deletion AC, -1385 - -1384
      deletion TG, -1250 - -1253 deletion GTGT. Firefly luciferase reporter gene
      systems showed that the luminosity of enhancer elements-luciferase reporter
      fusion gene in normal pituitary, prolactinoma treated without or with 0.25 mg per
      day per rat MLT were (13448.17+/-3012.74), (161831.67+/-60996.01), and
      (10212.17+/-634.71) OD units. Compared with the normal pituitary, the activity of
      PRL gene enhancer elements in prolactinoma was increased by 11 times (P<0.001).
      Compared with the prolactinoma, the activity of PRL gene enhancer elements in
      prolactinoma treated with MLT was decreased by 93.69% (P<0.001). Analysis of the
      space structure of PRL gene enhancer elements showed that the bending index in
      prolactinoma was higher than that in prolactinoma treated with MLT, which was
      higher than that in the normal pituitary. These results demonstrate that one of
      the important molecular mechanisms of MLT inhibiting the proliferation of
      prolactinoma is related to the reduction of enhancer elements mutation of PRL
      gene. These data also suggest that MLT-induced attenuation of enhancer elements
      mutation of PRL gene is involved in decreasing the bending index and attenuating
      the higher expression of PRL gene.

PMID- 15968427
TI  - [Expression of heat shock protein 70 mRNA in guinea pig cochlea with ototoxicity
      of gentamicin].
AB  - To examine the significance of heat shock protein 70 mRNA in ototoxicity resulted
      from gentamicin (GM), twenty healthy albino guinea pigs (200-250 g) of either sex
      with a positive Prier reflex were divided into two groups randomly. In GM group
      the animals received 100 mg/kg GM daily by intraperitoneal injection for 10 d. In
      saline control group the animals received 2.5 ml/kg saline daily by
      intraperitoneal injection for 10 d. Auditory brainstem response (ABR) thresholds
      were recorded in each animal before and 1 d after GM or saline administration.
      After the second ABR measurement, the expression of HSP70 mRNA in guinea pig
      cochlea was observed with in situ hybridization and image quantitative analysis
      system. The results showed that the threshold of ABR in the GM group was
      significantly higher than that of the saline control (P< 0.001). The expression
      of HSP70 mRNA was more intensive in stria vascularis, spiral ligament and spiral
      ganglion cells in the GM group than that of the saline control group. These
      results suggest that administration of gentamicin can induce the expression of
      HSP 70 mRNA in guinea pig cochlea, and that this effect may protect hearing
      function from ototoxicity.

PMID- 15968428
TI  - [Changes in electrophysiological and morphological properties of neuron in the
      ventral partition of medial geniculate body during the postnatal development of
      rats].
AB  - We investigated the electrophysiological and morphological characteristics of the
      neurons in the ventral partition of medial geniculate body (MGBv) in the rat
      during postnatal development (postnatal day 3-30, P3-30) with whole-cell patch
      clamp recording and intracellular labeling technique. The results are as follows:
      (1) There was an increase in the negativity of the resting membrane potential, a
      decrease in the input resistance and the time constant of the MGBv neurons of
      rats during the postnatal development; the amplitude, threshold and duration of
      the action potentials were also different on different postnatal days; (2) During
      the postnatal development, the changes in voltage-dependent ion channels
      dramatically influenced the waveform of action potential in the MGBv neurons.
      Application of 4-AP, a K(+)-channel blocker, reduced the amplitude and prolonged
      the durations of the action potentials in P6 neurons, and inactivated the neurons
      at the end of the pulse in P16 rats. Application of CdCl2 to block the voltage
      dependent Ca(2+)-channel decreased the amplitude and increased the duration of
      the action potential in P16 rats; (3) Biocytin staining revealed that immature
      MGBv cell had smaller somata and short, simple dendritic aborization. During
      postnatal development, the matured neurons had oval somata and 3-4 primary
      dendrities that radiated irregularly and projected outside the section; spines
      also appeared on the dendrites of the mature neurons. These results reveal that
      the morphologic and electrophysiological properties are not matured during early
      postnatal development, and that the electrophysiological and morphological
      features of the developing MGBv neurons are interrelated.

PMID- 15968429
TI  - Adrenomedullin reduces intracellular calcium concentration in cultured
      hippocampal neurons.
AB  - The effects of adrenomedullin (ADM) on intracellular calcium concentration
      ([Ca(2+)](i)) were investigated in cultured hippocampal neurons. Changes in
      [Ca(2+)](i) were detected by laser scanning confocal microscopy using Fluo 3-AM
      as the calcium fluorescent probe. [Ca(2+)](i) was represented by relative
      fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L)
      decreased the resting [Ca(2+)](i) in a concentration-dependent manner. (2)
      Calcitonin gene-related peptide receptor antagonist CGRP(8-37) significantly
      inhibited the effects of ADM. (3) ADM significantly reduced the increase in
      [Ca(2+)](i) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5
      trisphosphate (IP(3))-induced increase in [Ca(2+)](i), while did not influence
      ryanodine-evoked increase in [Ca(2+)](i). These results suggest that ADM reduces
      [Ca(2+)](i) in cultured hippocampal neurons through suppressing Ca(2+) release
      from IP(3)-sensitive stores. Although ADM does not alter resting Ca(2+) influx,
      it significantly suppresses Ca(2+) influx activated by high K(+). These effects
      may be partly mediated by CGRP receptors. ADM in the CNS may act as a
      cytoprotective factor in ischemic/hypoxic conditions.

PMID- 15968430
TI  - Experimental study on the new significant function domains of KCHIP1 protein.
AB  - Human K(v) channel interacting protein 1 (KCHIP1) is a new member of the neural
      calcium binding protein superfamily. Theoretically KCHIP1 has several calcium
      binding domains and two myristoylation sites. In this study, we demonstrated that
      the calcium binding domains and myristoylation sites were functional. The first,
      through running SDS-PAGE gel, we testified its ability of binding Ca(2+) with
      obvious discrepancy of the electrophoresis migrating rate after binding Ca(2+).
      Then, through the techniques of fused green fluorescence protein and site
      directed mutagenesis, we demonstrated that wild type KCHIP1 protein accumulated
      in the secretory vesicles of Golgi body. In contrast, its two mutated forms
      without myristoylation sites accumulated throughout the whole cytoplasm. These
      observations indicate that KCHIP1 protein has a myristoylation motif mediating
      the interaction between KCHIP1 protein and membrane.

PMID- 15968431
TI  - [Background chloride currents in fetal human nasopharyngeal epithelial cells].
AB  - To characterize the background current in fetal human nasopharyngeal epithelial
      cells and clarify its relationship with volume activated Cl(-) currents
      (I(Cl,vol)), whole-cell patch clamp and cell imaging techniques were employed.
      Under isotonic conditions, a background current [(5.9+/-2.1) pA/pF at +80 mV,
      n=21] was detected. The current presented a weak outward rectification and a
      negligible time-dependent inactivation. The current-voltage relationship showed
      that the reversal potential of the background current [(-0.73+/-1.7) mV, n=21]
      was close to the calculated equilibrium potential for Cl(-)(-0.9 mV). Application
      of extracellular hypertonic stimulation (440 mOsmol/L) suppressed the current by
      (59.6+/-7.1)% and the inhibition was reversible after returned to isotonic
      conditions. Bathing the cells in hypotonic solution (160 mOsmol/L) induced a
      volume-sensitive Cl(-) current. The Cl(-) channel blockers, tamoxifen (20
      micromol/L) and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) (100
      micromol/L), inhibited the background current by (74.0+/-5.2)% (P<0.01, n=5) and
      (60.9+/-8.9)% (P<0.01, n=6) at +80 mV and increased basal cell volume by (107.7+/
      2.9)% (P<0.01, n=25) and (104.4+/-2.4)% (P<0.01, n=19), respectively. The data
      indicate that Cl(-) current is an important component of the background current
      in fetal human nasopharyngeal epithelial cells. The background Cl(-) current is
      involved in volume activated Cl(-) current and basal cell volume regulation.

PMID- 15968432
TI  - Resveratrol inhibits neuronal discharges in rat hippocampal CA1 area.
AB  - The effects of resveratrol on the discharges of neurons in CA1 area of rat
      hippocampal slices were examined by using extracellular recording technique. The
      results are as follows: (1) In response to the application of resveratrol (0.05,
      0.5, 5.0 micromol/L, n=52) into the superfusate for 2 min, the spontaneous
      discharge rate of 46/52 (88.5%) neurons was significantly decreased in a dose
      dependent manner; (2) Application of L-glutamate (0.2 mmol/L) into the
      superfusate led to a marked increase in discharge rate of all 8 (100%) slices in
      an epileptiform pattern. The increased discharges were suppressed by application
      of resveratrol (5.0 micromol/L); (3) In 7 slices, perfusion of the selective L
      type calcium channel agonist, Bay K8644 (0.1 micromol/L), induced a significant
      increase in the discharge rate of 6/7 (85.7%) slices. The increased discharges
      were suppressed by application of resveratrol (5.0 micromol/L); (4) In 9 slices,
      perfusion of nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl
      ester (L-NAME, 50 micromol/L) into the superfusate significantly augmented the
      discharge rate of 7/9 (77.8%) slices. Resveratrol (5.0 micromol/L) applied into
      the superfusate reduced the increased discharges of all 7/7 (100%) neurons; (5)
      In 10 units, the large-conductance Ca(2+)-activated K(+) channel blocker
      (tetraethylammonium chloride, TEA, 1 mmol/L) significantly increased the
      discharge rate of 9/10 (90%) slices. Resveratrol (5.0 micromol/L) applied into
      the superfusate inhibited the discharges of 8/9 (88.9%) slices. These results
      suggest that resveratrol inhibits the electrical activity of CA1 neurons. This
      effect may be related to the blockade of L-type calcium channel and a subsequent
      reduction of calcium influx, and probably has no association with large
      conductance Ca(2+)-activated K(+) channel.

PMID- 15968433
TI  - Effects of resveratrol on delayed afterdepolarization and triggered activity
      induced by ouabain in guinea pig papillary muscles.
AB  - The purpose of this study was to investigate the effects of resveratrol on
      delayed afterdepolarization (DAD) and triggered activity (TA) induced by ouabain
      in guinea pig papillary muscles and the underlying mechanism. Action potentials
      were recorded using intracellular microelectrode technique. The results obtained
      are as follows: (1) DAD and TA induced by ouabain (1 micromol/L) were inhibited
      by pretreatment with resveratrol (30, 60, and 120 micromol/L) in a concentration
      dependent manner; (2) Pretreatment with N(G)-nitro-L-arginine methyl ester (L
      NAME, 1 mmol/L), a nitric oxide (NO) synthase inhibitor, failed to abolish the
      above effect of resveratrol (60 micromol/L ); (3) 5 micromol/L 17beta-estradiol
      (E(2)) or 30 micromol/L resveratrol had no effects on DAD and TA, however,
      resveratrol combined with E(2) at the same doses exerted significant inhibitory
      effects on DAD and TA; (4) Pretreatment with tamoxifen (TAM, 10 micromol/L), an
      inhibitor of estrogen receptor, also did not blocked the effects of resveratrol
      (60 micromol/L) on DAD and TA induced by ouabain. All these results indicated
      that resveratrol exerted an inhibitory effects on DAD and TA induced by ouabain,
      possibly by reducing calcium influx, which might not be mediated by NO and
      estrogen receptor. The antiarrhythmic effects of resveratrol may contribute to
      its cardioprotective action.

PMID- 15968434
TI  - [Melatonin improves vascular reactivity of endotoxemia rats].
AB  - The purpose of the present study was to investigate the effect of melatonin (MT)
      on the abnormal reactivity of thoracic aorta and pulmonary artery induced by
      lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four
      groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3)
      LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS
      (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first
      injection of MT another dose of MT was given. Six hours after LPS injection,the
      rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings
      (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was
      tested separately. The contraction response to phenylephrine (PE) and the
      endothelium-dependent relaxation response (EDRR) to ACh were observed with the
      isolated artery ring technique. Concentration-response curves were generated with
      ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and
      the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS
      significantly reduced the contraction response to PE compared with the vehicle
      group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group
      shifted downward. Although EDRR to ACh in the LPS group had the tendency to
      decrease but still showed no significant difference compared with the vehicle
      group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS
      group (P<0.01), while no effect on contraction response to PE in the LPS group
      was observed, compared with the vehicle group (P> 0.05). Compared with the LPS
      group, TARs in the LPS+MT group exhibited an increased contraction response to
      PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh
      of PARs in the LPS+MT group was improved significantly and there was no
      difference between the LPS+MT group and the vehicle group. The vascular
      reactivity was unaffected in MT group compared with the vehicle group in both
      TARs and PARs. SOD activity in the LPS +MT group increased significantly and the
      content of MDA decreased markedly compared with the LPS group. These results
      suggest that MT may improve the vascular reactivity in endotoxemia rats due to
      its antioxidant properties.

PMID- 15968435
TI  - Phytoestrogen genistein supplementation increases eNOS and decreases caveolin-1
      expression in ovariectomized rat hearts.
AB  - This study examined whether genistein influences the production of nitric oxide
      (NO) and expression of endothelial nitric oxide synthase (eNOS) and the
      modulators of eNOS activity in ovariectomized (OVX) rat hearts. Female mature
      Sprague-Dawley rats were subjected to bilateral ovariectomy, OVX rats were
      randomly divided into four groups: 17beta-estradiol (0.1 mg/kg, s.c. daily) was
      used as the positive control; low dose of genistein (0.5 mg/kg, s.c. daily); high
      dose of genistein (5.0 mg/kg, s.c. daily) and model. Sham operations as controls,
      the treatment lasted 6 weeks. Blood pressure, heart rate, plasma estradiol, heart
      and uterine weights were measured. Nitrite production in the myocardium was
      determined by nitrate reductase method. Protein level of eNOS, caveolin-1 and
      calmodulin was determined by Western blot. The results showed that nitrite
      production and eNOS protein in homogenized ventricular tissue was attenuated by
      approximately 53% and 67% in OVX rats compared with those in sham rats,
      respectively. Genistein increased nitrite production in rat heart in a dose
      dependent manner, genistein at the dose of 5 mg/kg.d(-1) resumed nitrite
      production to a level similar to that in sham operated rats. Administration of
      genistein also increased eNOS protein expression in OVX rats myocardium with a
      concomitant decrease in the expression of caveolin-1, an endogenous eNOS
      inhibitory protein. Another eNOS stimulatory protein, calmodulin, was unchanged
      in these treatments. These effects were also observed in rats treated with 17beta
      estradiol. Genistein at the dose of 5.0 mg/kg.d(-1) augmented uterine weight but
      this side effect in reproductive system was less than that of 17beta-estradiol.
      These results suggest that genistein supplementation and estrogen replacement
      therapy directly increase eNOS functional activity and NO production in the
      hearts of the OVX rats, but genistein has less side effects on the reproductive
      system than 17beta-estradiol.

PMID- 15968436
TI  - [Quantitative variation of vasoactive intestinal polypeptide and its receptor in
      rat liver during development].
AB  - Accumulated data have suggested that vasoactive intestinal polypeptide (VIP) and
      corresponding receptor (VIPR) are involved in the development of hematopoietic
      stem cells and liver growth. In the present study, radioimmunoassay, biomolecular
      interaction analysis and reverse transcriptation polymerase chain reaction were
      used to quantify VIP, VIPR and detect the subtype of VIPR in rat liver during
      development. VIP concentration of liver in fetal or neonatal rats was
      significantly lower than that of teens or adult rats (P<0.05). The binding
      capacities of VIPR in liver of immature rats were much greater than that of the
      adult rats (P<0.05). The tendency of change in VIP concentration was contrary to
      that of the binding capacity of VIPR in the liver of rats during development.
      VIPR-1 was expressed in rat liver in all phases of development. These results may
      be of benefit to the understanding of the mechanisms of liver growth and fetal
      liver hemopoiesis shift.

PMID- 15968437
TI  - [Effects of rotation on osteonectin and osteopontin mRNA level of cultured
      osteoblasts in rats].
AB  - Conditions of disuse such as bed rest, space flight, and immobilization result in
      decreased mechanical loading of bone, which is associated with reduced bone
      mineral density and increased fracture risk. Mechanisms involved in this process
      are not well understood except the suppression of osteoblast function. To
      investigate the effect of simulated weightlessness on mRNA level of extracellular
      matrix proteins, osteoblasts were rotated in horizontal plane as a model of
      simulated microgravity. Primordial osteoblasts of rats were grown for 2 d and
      then rotated for 24, 48 and 72 h, respectively. After isolating total RNA in
      cells, reverse transcription polymerase chain reaction (PT-PCR) was made to
      examine the mRNA level of osteopontin (OPN) and osteonectin (ON). Meanwhile, the
      levels of alkaline phosphatase (ALP) and osteocalcin (BGP) in the cultured medium
      were measured to evaluate the calcific function of cell. The expression of OPN
      and ON mRNA fell significantly after rotating for 24, 48 and 72 h, respectively.
      The contents of BGP descended significantly, meanwhile, the activity of ALP also
      showed a degressive tendency. Horizontal rotation decreased the expression of ON
      and OPN as well as diminished the secretion of BGP and ALP, which affected the
      calcific function of osteoblast. The results obtained suggest that depression of
      extracellular matrix proteins expression plays a key role in bone loss during
      weightlessness.

PMID- 15968438
TI  - [Changes in circadian sleep-wake and rest-activity rhythms during different
      phases of menstrual cycle].
AB  - The results of previous studies on the menstrual-related sleep changes were
      inconsistent. The menstrual-related circadian sleep-wake and rest-activity
      rhythms changes are still uncertain. Using actigraphic monitoring of wrist
      activity, we investigated the sleep-wake and rest-activity patterns of 12
      normally cyclic healthy women during reproductive life. Multivariate analyses
      were performed during the four phases of the menstrual cycle: menstrual phase
      (lst to 5th day of menstrual cycle), late follicular/peri-ovulation phase (11th
      to 15th day), early to mid luteal phase (18th to 23rd day) and late luteal phase
      (25th to 28th day), respectively. The variables of circadian sleep-wake pattern
      were similar in the four phases, except an increased tendency of the sleep
      latency in peri-ovulation phase compared with the early to mid-luteal phase (19+/
      18 vs 9+/-6), but unfortunately no statistical significance were found (P<0.10).
      Concerning the circadian patterning of rest and activity, the interdaily
      stability (IS) in menstrual phase was significantly higher than the early to mid
      luteal phase (P<0.05). In early to mid luteal phase, the M10 onset time was
      significantly earlier compared with that of the late follicular/peri-ovulation
      phase (P<0.05), and the cosinor peak time was significantly earlier compared with
      that of the late luteal phase (P<0.05). The circadian periodogram calculated the
      period length of the rhythm of average woman. The average length was (24.01+/
      0.29) h, and there was no significant difference among the four menstrual phases.
      The results suggest that the phase of circadian rest-activity rhythm may be
      modulated by the menstrual cycle, but the quantity and quality of the rest
      activity rhythm have no essential different, and that menstrual cycle may have no
      effects on the circadian sleep-wake rhythm in normally cyclic healthy women.

PMID- 15968439
TI  - [Effects of protein tyrosine kinase within the brainstem nucleus tractus
      solitarius on the ventilatory responses of peripheral chemoreflex].
AB  - The aim of the present study was to observe whether protein tyrosine kinase (PTK)
      within the nucleus tractus solitarius (NTS) was involved in the regulation of
      ventilatory responses of peripheral chemoreflex. The experiments were performed
      on anesthetized, immobilized and artificially ventilated rabbits. Peripheral
      chemoreflex was elicited by ventilating the animal with 10% O2-balance 90% N2.
      Changes in the peak amplitude and frequency of integrated phrenic nerve activity
      were observed. The ventilatory responses of peripheral chemoreflex following 0.1
      microl microinjection within the NTS of either PTK inhibitor genistein (10
      mol/L), AMPA glutamate receptor inhibitor CNQX (10 mol/L),or inactive PTK
      inhibitor daidzein (10 mol/L) were recorded. The results are as follows: Both
      genistein and CNQX attenuated the ventilatory responses of peripheral
      chemoreflex, while no changes occurred following daidzein. The amplitude of
      integrated phrenic nerve discharge and the phrenic burst frequency were decreased
      by (-21.77+/-6.93)% and (-24.70+/-7.61)% respectively after administration of
      genistein. CNQX resulted in similar decreases in the amplitude of phrenic nerve
      discharge (-27.13+/-7.63)% and the burst frequency (-21.34+/-4.88)%. In addition,
      the inhibitory effects of CNQX and genistein were the same whether they were
      applied alone or one after another, indicating that they had no cooperative
      effects. The results obtained suggest that PTK within the NTS regulates the
      peripheral chemoreflex control of respiration and that this regulation of PTK may
      be mediated through the phosphorylation of AMPA receptors in NTS neurons.

PMID- 15968440
TI  - Minimal access surgery: are we doing it right in Singapore?

PMID- 15968441
TI  - Charles Darwin (1809-1882): history's most famous naturalist.

PMID- 15968442
TI  - Serum lipid peroxidation and antioxidant enzyme levels in male and female
      diabetic patients.
AB  - INTRODUCTION: The depletion of defensive body chemicals called antioxidants may
      increase the risk of complications from the most common form of diabetes
      mellitus. This study aims to evaluate blood serum lipid peroxidation product
      (malondialdehyde), an antioxidant, in non-insulin dependent male and female type
      2 diabetic patients. METHODS: Blood serum samples were collected from the
      diabetic patients and non-diabetic healthy controls. Malondialdehyde (MDA) level,
      which is an index of endogenous lipid peroxidation, reduced glutathione and
      protein content of the serum were estimated. RESULTS: A significant elevation in
      MDA level and decrease in glutathione and protein content was observed in both
      male and female diabetic patients in comparison to non-diabetic controls.
      CONCLUSION: Our findings indicate that the increase in the lipid peroxidation
      product MDA and decline in glutathione-dependent antioxidant defences may appear
      early in non-insulin dependent type 2 diabetes mellitus patients before the
      development of secondary complications.

PMID- 15968443
TI  - Are all troponin assays equivalent in the emergency department?
AB  - INTRODUCTION: Cardiac-specific troponins (cTn) are recently-introduced, sensitive
      and specific markers of myocardial injury, and their absence should allow to
      safely exclude a coronary event. Various assays are commercially available but
      the relative advantage of each is not clear. Our objective was to compare the
      reliability of the two most commonly used troponin assays (cTnI and cTnT), in the
      emergency department (ED) for clinical decision when myocardial infarction (MI)
      or acute coronary syndrome (ACS) is suspected. METHODS: This prospective study
      included all patients arriving at the ED over a six-month period with chest pain
      or symptoms suggesting MI or ACS, in which diagnosis could not be confirmed due
      to absence of characteristic ECG features. All patients were tested with at least
      one of the two troponin assays available at the ED. RESULTS: Of the 54 included
      patients, ten (19%) were eventually diagnosed with MI/ACS. Qualitative assays for
      cTnI and cTnT identified the MI/ACS patients by both assays (respective positive
      predictive values of 0.5 and 0.7, and negative predictive values of 1.0 and 0.9).
      However, these assays were only partially correlated (R equals 0.49) and differed
      significantly. The quantitative assay for cTnI, but not for cTnT, discerned those
      who had MI/ACS (group A) from those who had other condition (group B) by their
      troponin levels (MI/ACS - 17.2 plus or minus 23.8 ng/ml versus others - 0.37 plus
      or minus 0.91 ng/ml, p is less than 0.001). CONCLUSION: In the ED, bedside assays
      of troponins are invaluable tools for the clinician, and their use is cost
      effective. However, in the recommended cutoffs levels, only troponin I but not
      troponin T allowed the safe discharge of patients not requiring acute hospital
      care.

PMID- 15968444
TI  - Omental infarction in children: imaging features with pathological correlation.
AB  - INTRODUCTION: Omental infarction is a rare occurrence in the paediatric
      population. It often presents as an acute abdomen that can mimic acute
      appendicitis and cholecystitis. METHODS: Six cases of omental infarction in
      children, proven on histopathology, were retrospectively reviewed for their
      clinical presentation and imaging findings on ultrasonography and computed
      tomography. RESULTS: These cases revealed clinical and imaging findings on
      computed tomography that were suggestive and helpful in the pre-operative
      diagnosis of omental infarction. Findings on ultrasonography were less specific.
      Histopathological specimens revealed findings of vasculitis in all cases.
      CONCLUSION: There are clinical and imaging features that will help in the pre
      operative diagnosis of this uncommon condition. We also postulate vasculitis as a
      possible underlying pathology for omental infarction.

PMID- 15968445
TI  - What barriers do primary care physicians face in the management of patients with
      chronic hepatitis B infection in primary care?
AB  - INTRODUCTION: Asymptomatic chronic hepatitis B virus (HBV) carriers, followed-up
      in primary care, present a challenge to primary care physicians as they encounter
      problems in monitoring this group of patients. The study aims to explore the
      barriers faced by primary care physicians in the management of patients with
      chronic hepatitis B infection in primary care. METHODS: Qualitative analysis of
      eight focus group discussions with 43 primary care physicians in Singapore was
      conducted. RESULTS: Primary care physicians highlighted the HBV carriers' poor
      compliance to disease monitoring as a major hurdle, attributing to their lack of
      understanding of the disease, state of denial, fear of stigmatisation in society,
      failure to perceive benefits, costs and reluctance of investigations due to
      physical discomfort. The carriers' health-seeking behaviour, such as doctor
      hopping and the use of traditional medication, were other barriers. The
      investigators noted that the physicians placed emphasis on passive disease
      monitoring, focusing on the investigation results when they reviewed the
      carriers. They were less proactive in explaining the disease's natural history
      nor discussing the possibility of definitive anti-viral treatment for suitable
      carriers. These physicians varied in their approaches in disease monitoring of
      chronic HBV infection. The fees-for-service healthcare system allowed the carrier
      to seek consultation from different doctors, which could result in disruption of
      disease surveillance. This was further compounded by the differential cost of
      investigations in private practices and government-aided polyclinics. The absence
      of a national HBV registry and recall system and waiting time for referral to
      specialist clinics in restructured hospitals, were other barriers. CONCLUSION:
      The management of HBV carriers in primary care could be enhanced by measures that
      eliminate the barriers involving the patient, doctor and healthcare system.

PMID- 15968446
TI  - The spectrum of beta-globin gene mutations in children with beta-thalassaemia
      major from Kota Kinabalu, Sabah, Malaysia.
AB  - INTRODUCTION: Beta-thalassaemia major is one of the commonest genetic disorders
      in South East Asia. The strategy for the community control of beta-thalassaemia
      major requires the characterisation of the spectrum of beta-globin gene mutations
      in any multi-ethnic population. There is only a single report of mutation
      analyses of the beta-globin gene in an isolated Kadazandusun community in Kota
      Belud, Sabah, Malaysia, which showed the presence of a common 45 kb deletion.
      METHODS: To confirm the observation that this large deletion is the commonest
      beta-globin gene mutation among the Kadazandusun and other indigenous populations
      in Sabah, Malaysia, we performed polymerase chain reaction (PCR) analysis of the
      beta-globin gene in ten children with beta-thalassaemia major attending the
      Thalassaemia Centre, Queen Elizabeth Hospital, the major paediatric referral
      centre in Kota Kinabalu, Sabah. RESULTS: The 45 kb deletion was confirmed to be
      the commonest mutation found in the Kadazandusun, Bajau and Murut populations,
      whereby it was detected in 19 out of the 20 (95 percent) alleles analysed. The
      other mutation was due to an IVS-1 position 1 G > T mutation. CONCLUSION: This
      finding confirmed the deletion in the homozygous state was associated with a
      severe phenotype. The reason for the predominance of this mutation in Kota
      Kinabalu is most likely to be due to founder effects and possibly intermarriages
      between the various ethnic groups. Prenatal diagnosis using PCR for this common
      mutation is feasible in this community. Medical workers and scientists at
      molecular diagnostic centres serving large South East Asian populations should
      incorporate a diagnostic strategy for this deletion in the appropriate
      population. Future studies on these indigenous ethnic groups in other areas and
      other groups in Sabah are required.

PMID- 15968447
TI  - Phaeochromocytoma of the urinary bladder.
AB  - The occurrence of urinary bladder paragangliomas is rare. A 12-year-old Chinese
      girl who presented with history of blurring of vision was found to have grade IV
      hypertensive retinopathy. Investigations revealed a phaeochromocytoma on the
      posterior wall of the urinary bladder. A partial cystectomy with right ureter
      reimplantation was undertaken and her hypertension was promptly controlled. The
      diagnosis and management of this rare tumour is discussed.

PMID- 15968448
TI  - Successful resuscitation after carbon dioxide embolism during laparoscopic
      assisted abdomino-perineal resection.
AB  - We report a 67-year-old woman who underwent laparoscopic-assisted abdomino
      perineal resection for rectal carcinoma. She sustained hypotension of 40/20 mmHg
      associated with bradycardia (heart rate 30 to 45 beats per minute) and an end
      tidal carbon dioxide level of zero when she was raised to a head-up position at
      the end of surgery to facilitate pelvic irrigation. Pulmonary air embolism was
      confirmed by aspiration of 15 millilitres of foamy blood from her central venous
      line. Resuscitation was successful and she recovered completely with no
      neurological deficits.

PMID- 15968449
TI  - Not all pustules are infective in nature: acute generalised exanthematous
      pustulosis causing pustular eruptions in an elderly woman.
AB  - Acute generalised exanthematous pustulosis (AGEP) is an adverse drug reaction
      that can occur in any age group. It is commonly mistaken as pustular psoriasis or
      cutaneous infection, resulting in unnecessary commencement of medications such as
      methotrexate and antibiotics that can cause harm to the patient or interact and
      adversely affect the efficacy of other medications. Early diagnosis of AGEP
      avoids unnecessary investigations and treatment, which not only can harm the
      patient but also escalate health care, as the condition is self-limiting. This
      case report illustrates AGEP secondary to Cefaclor occurring in a 72-year-old
      Chinese woman. Although the literature has documented the occurrence of AGEP with
      Cefaclor, the unique feature of this case is the occurrence of AGEP following
      repeated uneventful courses of Cefaclor. This case highlights that AGEP must
      never be forgotten in the work-up for pustular eruptions in an elderly patient.

PMID- 15968450
TI  - The painful scrotum: an ultrasonographical approach to diagnosis.
AB  - Many disease processes, including inflammation, testicular torsion, testicular
      trauma, and testicular cancer, may have a similar clinical presentation as a
      painful scrotum. Differentiation of these disease processes is important for
      proper management. High-resolution ultrasonography (US) combined with colour
      Doppler ultrasonography (CDUS) is the imaging modality of choice in evaluating
      these patients. Gray-scale US helps to better characterise scrotal lesions. CDUS
      demonstrates testicular perfusion which aids in reaching a specific diagnosis.
      This pictorial essay is intended to review the causes, US appearances of disease
      processes causing the painful scrotum, and examination pitfalls of scrotal US.

PMID- 15968451
TI  - Clinics in diagnostic imaging (104): Gastric trichobezoar (or hairball).
AB  - A 56-year-old man underwent triphasic computed tomography (CT) of the abdomen as
      part of his work-up for liver transplantation. A mottled, rounded lesion with a
      dense rim was noted in the gastric lumen, which remained unchanged in appearance
      in the arterial, portal venous, and delayed phases of the CT. Gastroscopy
      performed three days later confirmed the presence of trichobezoar. The foreign
      body was broken down into smaller pieces by an endoscopic snare and was passed
      out spontaneously. The clinical presentation, radiological findings, and
      management of trichobezoars are discussed.

PMID- 15968452
TI  - Separated but oceans apart and fathoms deep: the conjoined twins' legacy.

PMID- 15968456
TI  - White matter damage precedes that in gray matter despite similar magnetic
      resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats.
AB  - We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in
      neonatal rats would differ in white compared with gray matter as detected
      histologically or with magnetic resonance (MR) imaging methods. Maps of T2 and
      the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old
      rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of
      hypoxia), within the last 5-10 min of HI, and 1 h or 24 h after HI. Near the end
      of HI, ADC decreased and T2 increased in both cortical gray and subcortical white
      matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially
      recovered, but T2 remained increased and then increased further by 24 h post-HI.
      In contrast to the similar MR responses in white and gray matter, histological
      evidence for irreversible cell damage occurred in white matter earlier than in
      gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve
      fibers and an increase in TUNEL-positive cells were observed within white matter
      in the cingulum, whereas neurons within the cortical gray matter appeared normal.
      By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR
      imaging detected acute tissue edema following cerebral HI in both gray and white
      matter but did not distinguish between the early irreversible tissue injury
      detected histologically in white but not gray matter in this rather severe model
      of neonatal encephalopathy.

PMID- 15968458
TI  - Evidence for essential catalytic determinants for human erythrocyte pyrimidine 5'
      nucleotidase.
AB  - Human erythrocyte pyrimidine 5'-nucleotidase, PN-I, catalyzes the
      dephosphorylation of pyrimidine nucleoside monophosphates. The enzyme also
      possesses phosphotransferase activity, transferring phosphate groups between
      pyrimidine nucleoside monophosphates and various pyrimidine nucleosides.
      Deficiency of the enzyme activity is associated with a hemolytic anemia. PN-I
      cDNA has been expressed in Escherichia coli, yielding a fully active recombinant
      enzyme, which was purified to homogeneity and extensively characterized. Multiple
      sequence alignment of PN-I and homologues proteins revealed the existence of
      conserved regions, whose importance in catalysis was examined by performing
      experiments designed to intercept covalent intermediates as strongly suggested by
      our previous kinetic studies. Furthermore, a functional analysis of the enzyme
      was carried out through site-directed mutagenesis designed on the basis of the
      sequence of the identified conserved regions as well as mutations observed in PN
      I-deficient patients.

PMID- 15968457
TI  - Neuroprotection induced by the adenosine A2A antagonist CSC in the 6-OHDA rat
      model of parkinsonism: effect on the activity of striatal output pathways.
AB  - In Parkinson's disease (PD), the striatal dopamine depletion and the following
      overactivation of the indirect pathway of the basal ganglia leads to very early
      disinhibition of the subthalamic nucleus (STN) that may contribute to the
      progression of PD by glutamatergic overstimulation of the dopaminergic neurons in
      the substantia nigra. Adenosine A2A antagonism has been demonstrated to attenuate
      the overactivity of the striatopallidal pathway. To investigate whether
      neuroprotection exerted by the A2A antagonist 8-(3-chlorostyryl)caffeine (CSC)
      correlates with a diminution of the striatopallidal pathway activity, we have
      examined the changes in the mRNA encoding for enkephalin, dynorphin, and
      adenosine A2A receptors by in situ hybridization induced by subacute systemic
      pretreatment with CSC in rats with striatal 6-hydroxydopamine(6-OHDA)
      administration. Animals received CSC for 7 days until 30 min before 6-OHDA
      intrastriatal administration. Vehicle-treated group received a solution of
      dimethyl sulfoxide. CSC pretreatment partially attenuated the decrease in nigral
      tyrosine hydroxylase immunoreactivity induced by 6-OHDA, whereas no modification
      of the increase in preproenkephalin mRNA expression in the dorsolateral striatum
      was observed. The neuroprotective effect of the adenosine A2A antagonist CSC in
      striatal 6-OHDA-lesioned rats does not result from a normalization of the
      increase in striatal PPE mRNA expression in the DL striatum, suggesting that
      other different mechanisms may be involved.

PMID- 15968459
TI  - The Lac repressor provides a reversible gene expression system in
      undifferentiated and differentiated embryonic stem cell.
AB  - Control of mammalian gene promoters by the bacterial LacI repressor provides
      reversible regulation and dose-response levels of derepressed expression by the
      lactose analog isopropyl thiogalactose (IPTG). Here, we show that insertion of
      LacI-binding sites in the ubiquitous beta-actin promoter confers a strong and
      dose-dependent IPTG-regulatable expression of transiently transfected reporter
      genes in mouse embryonic stem (ES) cells expressing LacI. We established ES cell
      lines stably expressing reporter genes under inducible control and found a five-
      to tenfold IPTG induction of transgene expression. The kinetics of induction is
      rapid and stable, and can be rapidly reversed after IPTG removal. Importantly,
      this regulatable expression was maintained throughout the differentiation process
      of ES cells, and observed in individual differentiated cardiomyocyte-like cells
      and neuronal-like cells. This reversible system is the first to function from
      undifferentiated to individual well-differentiated ES cells, providing a very
      useful tool to understand molecular mechanisms underlying ES cell self-renewal,
      commitment and differentiation.

PMID- 15968460
TI  - Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for
      drug discovery.
AB  - Acetyl-coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism
      in most living organisms. Mice deficient in ACC2 have continuous fatty acid
      oxidation and reduced body fat and body weight, validating this enzyme as a
      target for drug development against obesity, diabetes and other symptoms of the
      metabolic syndrome. ACC is a biotin-dependent enzyme and catalyzes the
      carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic
      activities, biotin carboxylase (BC) and carboxyltransferase (CT). ACC is a multi
      subunit enzyme in most prokaryotes, whereas it is a large, multi-domain enzyme in
      most eukaryotes. The activity of the enzyme can be controlled at the
      transcriptional level as well as by small molecule modulators and covalent
      modification. This review will summarize the structural information that is now
      available for both the BC and CT enzymes, as well as the molecular mechanism of
      action of potent ACC inhibitors. The current intense research on these enzymes
      could lead to the development of novel therapies against metabolic syndrome and
      other diseases.

PMID- 15968461
TI  - The HERC proteins: functional and evolutionary insights.
AB  - HERC proteins are defined as containing both HECT and RCC1-like domains in their
      amino acid sequences. Six HERC genes have turned up in the human genome which
      encode two different sorts of polypeptides: while the small HERC proteins possess
      little more than the two aforementioned domains, the large ones are giant
      proteins with a plethora of potentially important regions. It is now almost 10
      years since the discovery of the first family member and information is starting
      to accumulate pointing to a general role for these proteins as ubiquitin ligases
      involved in membrane-trafficking events. In this review, the available data on
      these six members are discussed, together with an account of their evolution.

PMID- 15968462
TI  - Cell-penetrating peptides: tools for intracellular delivery of therapeutics.
AB  - The main problem of therapeutic efficiency lies in the crossing of cellular
      membranes. Therefore, significant effort is being made to develop agents which
      can cross these barriers and deliver therapeutic agents into cellular
      compartments. In recent years, a large amount of data on the use of peptides as
      delivery agents has accumulated. Several groups have published the first positive
      results using peptides for the delivery of therapeutic agents in relevant animal
      models. These peptides, called cell-penetrating peptides (CPPs), are short
      peptides (fewer than 30 residues) with a net positive charge and acting in a
      receptor- and energy-independent manner. Here, we give an extensive review of
      peptide-mediated delivery systems and discuss their applications, with particular
      focus on the mechanisms leading to cellular internalization.

PMID- 15968463
TI  - The glycinergic control of spinal pain processing.
AB  - Alterations in synaptic transmission within the spinal cord dorsal horn play a
      key role in the development of pathological pain. While N-methyl-D-aspartate
      (NMDA) receptors and activity-dependent synaptic plasticity have been the focus
      of research for many years, recent evidence attributes very specific functions to
      inhibitory glycinergic and gamma-aminobutyric acid (GABA)-ergic neurotransmission
      in the generation of inflammatory and neuropathic pain. The central component of
      inflammatory pain originates from a disinhibition of dorsal horn neurons, which
      are relieved from glycinergic neurotransmission by the inflammatory mediator
      prostaglandin E2 (PGE2). PGE2 activates prostaglandin E receptors of the EP2
      subtype and leads to a protein kinase A-dependent phosphorylation and inhibition
      of glycine receptors containing the alpha3 subunit (GlyRalpha3). This GlyRalpha3
      is distinctly expressed in the superficial dorsal horn, where nociceptive
      afferents terminate. Other but probably very similar disinhibitory mechanisms may
      well contribute to abnormal pain occurring after peripheral nerve injury.

PMID- 15968464
TI  - Chromosome 13 dementias.
AB  - The importance of cerebral amyloid deposition in the mechanism of
      neurodegeneration is still debatable. Classic arguments are usually centered on
      amyloid beta(Abeta) and its role in the neuronal loss characteristic of
      Alzheimer's disease, the most common form of human cerebral amyloidosis. Two non
      Abeta cerebral amyloidoses, familial British and Danish dementias (FBD and FDD),
      share many aspects of Alzheimer's disease, including the presence of
      neurofibrillary tangles, parenchymal preamyloid and amyloid deposits, cerebral
      amyloid angiopathy and a variety of amyloid-associated proteins and inflammatory
      components. Both early-onset conditions are linked to specific mutations at or
      near the stop codon of the chromosome 13 gene BRI2 that cause generation of
      longer-than-normal protein products. Furin-like processing of these longer
      precursors releases two de novo-created peptides, ABri and ADan, which deposit as
      amyloid fibrils in FBD and FDD, respectively. Due to the similar pathology
      generated by completely unrelated amyloid subunits, FBD and FDD, collectively
      referred to as chromosome 13 dementias, constitute alternative models for
      studying the role of amyloid deposition in the mechanism of neuronal cell death.

PMID- 15968465
TI  - Synaptic dysfunction in Huntington's disease: a new perspective.
AB  - Huntington's disease (HD) is caused by a polyglutamine expansion in the protein
      huntingtin and is characterized by intraneuronal inclusions and widespread
      neuronal death at the late stage of the disease. In research, most of the
      emphasis has been on understanding the cell death and its mechanisms. Until
      recently, it was believed that the vast majority, if not all, of the symptoms in
      HD are a direct consequence of neurodegeneration. However, increasing evidence
      shows that subtle alterations in synaptic function could underlie the early
      symptoms. It is of particular interest to understand the nature of this neuronal
      dysfunction. Normal huntingtin interacts with various cytoskeletal and synaptic
      vesicle proteins that are essential for exocytosis and endocytosis. Altered
      interactions of mutant huntingtin with its associated partners could contribute
      to abnormal synaptic transmission in HD. This review describes recent advances in
      understanding synaptic dysfunction in HD.

PMID- 15968466
TI  - Dual modes of 5-(N-ethyl-N-isopropyl)amiloride modulation of apical dipeptide
      uptake in the human small intestinal epithelial cell line Caco-2.
AB  - Selective pharmacological Na+/H+ exchange (NHE) inhibitors were used to identify
      functional NHE isoforms in human small intestinal enterocytes (Caco-2) and to
      distinguish between direct and indirect effects on transport via the intestinal
      di/tripeptide transporter hPepT1. The relative potencies of these inhibitors to
      inhibit 22Na+ influx identifies NHE3 and NHE1 as the apical and basolateral NHE
      isoforms. The Na+-dependent (NHE3-sensitive) component of apical dipeptide ([14C]
      Gly-Sar) uptake was inhibited by the selective NHE inhibitors with the same order
      of potency observed for inhibition of apical 22Na+ uptake. However, 5-(N-ethyl-N
      isopropyl) amiloride (EIPA) also reduced [14C]Gly-Sar uptake in the absence of
      Na+ and this inhibition was concentration and pH (maximal at pH 5.5) dependent.
      NHE3 inhibition by S1611 and S3226 modulates dipeptide uptake indirectly by
      reducing the transapical driving force (H+ electrochemical gradient). EIPA (at
      100 microM) has similar effects, but at higher concentrations (> 200 microM) also
      has direct inhibitory effects on hPepT1.

PMID- 15968467
TI  - Genomic sources of regulatory variation in cis and in trans.
AB  - Regulatory variation results from genetic changes with both cis and trans acting
      effects on gene expression. Here I describe the types of genetic variants that
      alter cis and trans regulation and discuss differences in the potential for cis
      and trans changes among different classes of genes. I argue that the molecular
      function of the protein encoded by each gene and how the gene is wired into the
      genomic regulatory network may influence its propensity for cis and trans
      regulatory changes.

PMID- 15968468
TI  - Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition
      mechanism and perspective for the future.
AB  - Tyrosinase is known to be a key enzyme in melanin biosynthesis, involved in
      determining the color of mammalian skin and hair. Various dermatological
      disorders, such as melasma, age spots and sites of actinic damage, arise from the
      accumulation of an excessive level of epidermal pigmentation. In addition,
      unfavorable enzymatic browning of plant-derived foods by tyrosinase causes a
      decrease in nutritional quality and economic loss of food products. The
      inadequacy of current conventional techniques to prevent tyrosinase action
      encourages us to seek new potent tyrosinase inhibitors. This article overviews
      the various inhibitors obtained from natural and synthetic sources with their
      industrial importance.

PMID- 15968469
TI  - The therapeutic potential of tumor necrosis factor for autoimmune disease: a
      mechanistically based hypothesis.
AB  - Excess levels of tumor necrosis factor-alpha (TNF-alpha) have been associated
      with certain autoimmune diseases. Under the rationale that elevated TNF-alpha
      levels are deleterious, several anti-TNF-alpha therapies are now available to
      block the action of TNF-alpha in patients with autoimmune diseases with a chronic
      inflammatory component to the destructive process. TNF-alpha antagonists have
      provided clinical benefit to many patients, but their use also is accompanied by
      new or aggravated forms of autoimmunity. Here we propose a mechanistically based
      hypothesis for the adverse events observed with TNF-alpha antagonists, and argue
      for the opposite therapeutic strategy: to boost or restore TNF-alpha activity as
      a treatment for some forms of autoimmunity. Activation defects in the
      transcription factor nuclear factor kappaB leave autoreactive T cells sensitive
      to TNF-alpha-induced apoptosis. Treatment with TNF-alpha, by destroying
      autoreactive T cells, appears to be a highly targeted strategy to interrupt the
      pathogenesis of type 1 diabetes, lupus and certain forms of autoimmunity.

PMID- 15968470
TI  - Anesthesia increases circulating glutamate in neurosurgical patients.
AB  - BACKGROUND: The excitotoxic amino acid glutamate is known to aggravate pre
      existing neuropathology. Since volatile anesthetics increase plasma amino acid
      levels, we investigated if the anesthetics isoflurane and propofol increase
      plasma and cerebrospinal fluid (CSF) glutamate in neurosurgical patients.
      METHODS: In discectomized patients (n = 15), plasma glutamate was determined at
      30 minute intervals before and during isoflurane anesthesia. In craniotomized
      patients (n = 66), plasma glutamate was assessed during and up to 24 hours after
      routine isoflurane or propofol anesthesia. CSF samples were withdrawn upon
      opening of the dura, before surgical manipulations. FINDINGS: During isoflurane
      anesthesia, plasma glutamate was significantly and reversibly increased in
      discectomized and craniotomized patients compared to healthy controls (56+/-6
      microM; p<0.05), which was mostly sustained in male patients (males: 126+/-12 vs.
      females: 96+/-6 microM; p<0.05). With propofol, plasma glutamate was increased
      equally in men and women but to a lesser extent than with isoflurane (mean: 72+/
      7 microM). CSF glutamate was significantly increased during isoflurane and
      propofol anesthesia compared to control lumbar CSF (1.2+/-0.1 microM; p<0.0001),
      being more prominent in patients with pre-existing brain edema receiving
      isoflurane (76+/-8 vs. propofol: 40+/-6 microM; p<0.05). CONCLUSIONS: The
      significant increases in plasma and CSF glutamate which were mostly sustained
      during isoflurane compared to propofol anesthesia should prompt the
      identification of anesthetic agents which do not impose a possible burden of
      glutamate-mediated excitotoxicity in patients with underlying compromised
      cerebral homeostasis. Detailed neuropsychological investigations following
      different anesthesia regimen are important to determine if transient elevations
      in CSF and plasma glutamate levels are of clinical relevance.

PMID- 15968471
TI  - A prospective study of a series of 356 patients with supratentorial spontaneous
      intracerebral haematomas treated in a Neurosurgical Department.
AB  - BACKGROUND: Spontaneous supratentorial intracerebral haemorrhages (SSIH) carry
      high morbidity and mortality rates. At present, the proper role of surgery is not
      clear and data from the International STICH trial have not clarified this
      challenging question. On the other hand, few prospective studies have measured
      long term survival regardless of the treatment and clinical condition of the
      patient. PATIENTS AND METHODS: We prospectively collected data from all SSIH
      patients (n = 356) admitted at a tertiary reference hospital over a 40-month time
      period regardless of their clinical condition and treatment received. Among data
      investigated were preclinical neurological state, GCS on admission, history of
      systemic hypertension and treatment (surgical or conservative). Clinical factors
      influencing mortality at 1-year follow-up were analysed statistically by
      univariable and multivariable methods. FINDINGS: We found that patients in the
      eighth decade were the most frequent. Hypertension was present in 47% of
      patients. Based on the prehospitalisation modified Rankin Scale, 305 (86%)
      patients were independent for activities of daily living (ADL). At 12-months
      follow-up, 91 (46% of alive patients) remained independent for ADL. The surgical
      rate was 22%. Although it was not a randomised study, we did not find a
      significantly different mortality rate according to whether the patient was
      treated surgically or conservatively. Overall, the mortality rate was 44% (157
      patients) with a 79% of deaths taking place in the first 30 days after admission.
      CONCLUSIONS: This study underscores the high mortality rate of SSIH, especially
      so in the first month after admission. Among the subgroup of patients clinically
      independent before the haemorrhagic stroke, only 29.8% remained independent one
      year after the event. We did not find any statistically significant difference in
      mortality according to treatment modality received (surgical vs conservative)
      although treatment assignment was not randomised. Among other clinical factors,
      pre-ictal functional status, age, level of consciousness on admission and volume
      of haemorrhage strongly influence mortality as determined at the 1-year follow
      up.

PMID- 15968472
TI  - Characterisation of the welsh onion isolate of Shallot yellow stripe virus from
      China.
AB  - The host range and nucleotide sequence of shallot yellow stripe virus (SYSV) from
      welsh onion in Shandong province, China is described. Of the plants tested, only
      shallot and welsh onion became infected but most shallot plants were symptomless.
      The complete sequence of one isolate (10429 nt) and the 3'-terminal 3540 nts of a
      second isolate were determined. They had c. 90% nt identity to one another and to
      published (partial) sequences of SYSV. SYSV was most closely related to onion
      yellow dwarf virus (OYDV) and resembled it in having a much larger P3 protein
      than other species in the genus.

PMID- 15968473
TI  - Phylogenetic analysis of the hexon loop 1 region of an adenovirus from psittacine
      birds supports the existence of a new psittacine adenovirus (PsAdV).
AB  - Adenovirus infections in psittacine birds have been well known. Most of these
      infections were caused by fowl adenoviruses (FAdV). In this study, liver samples
      showing typical histological signs of an adenovirus infection were collected from
      Poicephalus spp. with acute disease. A PCR amplifying the variable loop 1 region
      of the hexon gene was developed using primers located in two conserved pedestal
      regions. A PCR product of approximately 590 bp in size was amplified and
      sequenced. The sequence obtained grouped outside of the FAdV reference strains of
      the 12 serotypes as well as egg drop syndrome virus and turkey adenovirus 3
      indicating that a new avian adenovirus was detected. In comparison to the FAdV
      reference strains, the percentage of identical nucleotides ranged between 60.3
      and 67.0 and that of identical amino acids (aa) between 51.3 and 61.0.
      Furthermore, 37 unique aa exchanges were observed; out of these, 27 are located
      in the 4 hypervariable regions of loop 1, which encode the serotype-specific
      epitopes. The g/c content, the isoelectric point and the charge of the amplified
      fragment, however, are in the range as those of group I avian adenoviruses. It
      was proposed, therefore, to designate this new adenovirus as psittacine
      adenovirus (PsAdV).

PMID- 15968474
TI  - Genetic comparison of large fragment of the 5'untranslated region among foot-and
      mouth disease viruses with special reference to serotype Asia1.
AB  - Foot-and-mouth disease (FMD), the most economically important disease of cloven
      hoofed animals, is endemic in India. Sequence analysis revealed that phylogenetic
      grouping of type Asia1 field isolates on the basis of the large fragment of the
      5'untranslated region (5'LF-UTR) was quite similar to that based on the sequences
      of the capsid-coding (VP1) region of the same viruses. The existence of two
      distinct lineages of type Asia1 suggested by the study on the VP1 region was
      further supported by the detection of a difference in length and predicted
      secondary structure of the 5'LF-UTR between the two lineages. Sequence
      variability between the isolates of the two lineages was also observed within the
      different domains of the internal ribosome entry site (IRES) around conserved
      motifs like the GNRA,- RAAA,- and the polypyrimidine tract. Certain group and
      lineage-specific signature nucleotides pertaining to FMDV type Asia1 in the 5'LF
      UTR have been identified. The present study shows that the 5'LF-UTR of FMDV
      serotype Asia1 field isolates are variable in relation to the length and probable
      secondary structure of the IRES.

PMID- 15968475
TI  - Characterization of a naturally occurring recombinant isolate of Grapevine
      fanleaf virus.
AB  - The naturally occurring Grapevine fanleaf virus (GFLV) recombinant isolate A17b
      was recovered from its grapevine host by sap inoculation and serial passages onto
      Gomphrena globosa, a pseudo local lesion herbaceous host, and Chenopodium quinoa,
      a systemic herbaceous host, to characterize some of its biological properties.
      Sequence analysis of the CP gene, in which a recombinational event was previously
      detected, demonstrated the genetic stability of recombinant isolate A17b over a 5
      year period in its natural host as well as in C. quinoa. Also, recombinant
      isolate A17b was graft transmissible, as shown by an in vitro heterologous
      approach, and transmitted by the nematode Xiphinema index as readily as
      nonrecombinant GFLV isolates. Furthermore, despite a lower pathogenicity on
      Chenopodium amaranticolor, recombinant isolate A17b had a similar host range and
      induced similar symptoms in type and severity to nonrecombinant GFLV isolates.
      Interestingly, the use of infectious chimeric RNA2 transcripts in combination to
      RNA1 transcripts of GFLV strain F13 suggested no implication of the recombination
      event in the CP gene of isolate A17b in the reduced pathogenicity on C.
      amaranticolor. Altogether, recombinant isolate A17b had similar biological
      properties to GFLV nonrecombinant isolates.

PMID- 15968476
TI  - Molecular characterization of banana virus X (BVX), a novel member of the
      Flexiviridae family.
AB  - A novel virus was identified in banana (Musa spp). Analysis of the last 2917
      nucleotides of its positive strand genomic RNA showed five open reading frames
      corresponding, from 5' to 3', to a truncated ORF coding for a replication
      associated protein, three ORFs coding for a movement-associated triple gene block
      (TGB) and a capsid protein (CP) gene. This genome organization is similar to that
      of some members of the Flexiviridae family such as potexviruses and foveaviruses.
      This virus was named Banana virus X (BVX). Comparative sequence analysis showed
      that BVX is only distantly related to other members of the Flexiviridae family,
      in which it appears to define a new genus. BVX produces defective RNAs derived
      from its genomic RNA by non-homologous recombination. Three distinct pairs of
      donor/acceptor recombination sites involving short direct nucleotide repeats were
      characterized, accounting for deletions of 1268, 1358 and 1503 nucleotides.
      Contrary to the situation encountered for Potexviruses, these recombination sites
      are located within the TGB1 and CP genes and result in a truncated TGB1 protein.

PMID- 15968477
TI  - Integration of mutations responsible for the attenuated phenotype of Pepper mild
      mottle virus strains results in a symptomless cross-protecting strain.
AB  - An enhanced attenuated strain of Pepper mild mottle virus (PMMoV) was constructed
      by incorporating mutations that affect viral attenuation from three reported
      attenuated strains of PMMoV, which causes serious economic losses in the
      production of green pepper in Japan. The new strain caused no symptoms on pepper
      plants and protected them from infection by a wild-type strain. The mutations
      responsible for viral attenuation were located in the intervening region (IR) of
      the 126-kDa/183-kDa proteins. The mutations had synergistic effects in terms of
      the attenuation of symptoms and decreased the accumulation of the viral coat
      protein in infected pepper plants. In this paper, we propose an efficient method
      for the improvement of attenuated viruses by reverse genetics in plant viruses.

PMID- 15968478
TI  - The effect of oxygen exposure on pentacene electronic structure.
AB  - We use ultraviolet photoelectron spectroscopy to investigate the effect of oxygen
      and air exposure on the electronic structure of pentacene single crystals and
      thin films. It is found that O(2) and water do not react noticeably with
      pentacene, whereas singlet oxygen/ozone readily oxidize the organic compound.
      Also, we obtain no evidence for considerable p-type doping of pentacene by O(2)
      at low pressure. However, oxygen exposure lowers the hole injection barrier at
      the interface between Au and pentacene by 0.25 eV, presumably due to a
      modification of the Au surface properties.

PMID- 15968479
TI  - Comparative assessment of pedicle morphology of the lumbar spine in various
      degenerative diseases.
AB  - Measurement of the morphological dimensions of the pedicles of the lumbar spine
      was conducted using computed tomography (CT) to clarify the difference in pedicle
      morphology among different lumbar degenerative diseases. The subjects were 136
      patients with lumbar spinal disorders who underwent myelography followed by CT
      scans. They were divided into four groups, that is a group of 25 patients with
      degenerative spondylolisthesis (DS group), a group of 54 patients with lumbar
      canal stenosis (LCS group), a group of 42 patients with lumbar disc herniation
      (LDH group), and a control group of 15 patients with spinal cord tumor in
      cervicothoracic region but without lumbar diseases (control group). Measurements
      of the transverse diameter, axial length, and axial angle of the pedicles were
      performed on CT slices obtained at the middle of the pedicle. The transverse
      diameter was the width of the isthmus, the axial length was the distance between
      the anterior of the vertebral body and the posterior of the vertebral arch on a
      line perpendicular to the line bisecting the isthmus, and the axial angle was the
      angle between the line perpendicular to the line bisecting the isthmus and the
      midline of the vertebral body. While there were no significant differences in the
      mean transverse diameter or axial length among the four groups, the mean axial
      angle was significantly smaller in the DS and LCS groups when compared to that in
      the LDH and control groups. In the DS and LCS groups, the pedicles were more
      sagitally oriented than in the LDH and control groups. Such difference in the
      axial angle of the pedicles in different lumbar diseases should be taken into
      consideration when placing at the insertion of pedicle screws, because precise
      orientation of screw insertion would scarcely allow penetration of the pedicle
      wall.

PMID- 15968480
TI  - Morphometric study of the nerves entering into the coracobrachialis muscle.
AB  - The nerves entering into the coracobrachialis muscle are the musculocutaneous
      nerve (MC) and the nerve (usually consists of several thin branches) branches to
      the coracobrachialis. These thin branches enter the coracobrachialis proximal to
      the MC. The thin branches and the MC are susceptible to injury during coracoid
      process transfer. The purpose of this study is (1) to reveal the number and
      origin of the thin branches and (2) especially to report the morphometric
      information about the two distances between the coracoid process and the points
      where the first thin branch and the MC enter the coracobrachialis. These
      distances were named as the "distance T1" and the "distance D," respectively.
      Forty-two cadaver upper extremities were used and the distance between the
      coracoid process and the medial epicondyle of the humerus as the "arm length" was
      measured. The "ratio T1" was calculated by dividing the distance T1 by the arm
      length. The "ratio D" was calculated by dividing the distance D by the arm
      length. The number of the thin branches varied between one and four. In the most
      common type, there were two thin branches (45%). All of the thin branches
      originated from the MC. The mean distance T1, distance D and arm length were
      found as 41.5, 62 and 304.5 mm, respectively. The mean ratio T1 and ratio D were
      determined as 0.13 (approximately 1/8) and 0.20 (=1/5), respectively. The
      findings about the number and origin of the thin branches may contribute to the
      anatomy of the nerve to the coracobrachialis. The shoulder surgeon may calculate
      the predicted distance T1 and distance D of any upper extremity, dividing its arm
      length by eight and five, respectively.

PMID- 15968482
TI  - [Cost reductions and their effects on drug research].
AB  - There are numerous reasons for the decline in pharmaceutical R and D in Germany.
      To mention the most important: inadequate public sponsoring of R and D activities
      and the late onset of biotechnology support. Cost containment in drug spending is
      also a major hurdle for R and D investments. An overview for the time span from
      1992 to 2001, initiated by the OECD organization, reveals that average price
      increases for drugs in Germany are at their lowest levels as compared to other
      markets such as Canada, the USA, Australia and the remaining European markets. In
      addition, R and D productivity has, in general, decreased. Independent of
      locations and despite the use of new technologies, it has even worsened. This
      situation has not changed through the introduction of biotech products. For
      Germany, it is recommended to increase the investment in R and D, in order to
      reduce bureaucratic overheads and to better estimate innovation.

PMID- 15968483
TI  - [Drug utilization and pharmaceutical cost-containment in germany-perspectives 1
      year after enactment of the GMG].
AB  - After 3 decades of health care cost containment in Germany, enactment of the most
      recent reform (Health Insurance Modernization Act, GMG) marks a watershed insofar
      as, apparently, the potential has been largely exhausted for further savings in
      pharmaceutical spending. Yet the new drugs segment maintains its role as a growth
      driver, owing to the continuing shift from older to new, and frequently more
      expensive, products. This observation holds true even after introducing phase 2
      reference pricing, covering so-called me too products. Health economic analyses
      would be required to better differentiate pharmaceutical products based on their
      incremental cost-effectiveness ratio. However, the opportunity was missed with
      the GMG to introduce formal health-economic evaluations and thus overcome the
      counterproductive silo mentality associated with traditional German component
      management. International experience from Australia, Canada, and the United
      Kingdom suggests that economic evaluations, while informing rational
      reimbursement decisions, may in fact contribute to increasing pharmaceutical
      expenditures. Further tightening of pharmaceutical component management in
      Germany may result in increasing inefficiencies due to underuse of effective
      products; furthermore, it appears conceivable that ("second order") dynamic
      inefficiencies and, hence, social costs might be the consequence of reduced
      pharmaceutical research and development expenditures.

PMID- 15968484
TI  - [New developments in the diagnosis and therapy of acute bacterial meningitis].
AB  - BACKGROUND: Acute bacterial meningitis is a medical emergency. Despite advances
      in the diagnosis and treatment it continues to have a high case-fatality rate and
      high rates of long-term neurologic sequelae. ETIOLOGY: Since the widespread use
      of the vaccine for Haemophilus influenzae type B, Streptococcus pneumoniae has
      replaced it as the most common cause of acute community-acquired bacterial
      meningitis in industrialized countries. The rising incidence of beta-lactam
      resistant pneumococci has to be considered when choosing a regimen for empiric
      antibiotic therapy. DIAGNOSIS: The clinical diagnosis remains difficult, as
      absent clinical meningeal signs do not exclude bacterial meningitis. If bacterial
      meningitis is considered a possible diagnosis, empiric antibiotic therapy should
      be initiated without any delay. Prior blood cultures and, if not contraindicated,
      a lumbar puncture should be performed. Based on new evidence, a screening cranial
      computed tomography to rule out raised intracranial pressure prior to lumbar
      puncture is recommended only for patients with defined risk factors (age > 60
      years; preexisting immunodeficiency, immunosuppression, or neurologic diseases;
      recent seizures; any pathologic finding in the neurologic examination other than
      meningism). TREATMENT: Empiric antibiotic therapy should be initiated before
      cranial computed tomography. Adjuvant dexamethasone therapy initiated with or
      prior to the antibiotic therapy reduces mortality and morbidity for patients with
      pneumococcal meningitis without increasing the rate of side effects.

PMID- 15968485
TI  - [Chlamydia pneumoniae--a new risk factor for calcific aortic stenosis?].
AB  - BACKGROUND: Nonrheumatic, calcific aortic stenosis is the main heart valve
      disease and the main cause of heart valve replacement in the elderly. Recent
      studies suggest that it is based on a chronic inflammatory process. The
      pathogenetic mechanisms, however, are unclear. METHODS: A MEDLINE search was
      conducted for the phrases "chlamydia pneumoniae" and "aortic valve", and all
      articles published between 1966 and May 2004 were evaluated. Data presented as
      letter or congress abstract was also included. RESULTS: Clinical and
      histopathologic studies demonstrate an association of calcific aortic stenosis
      and cardiovascular risk factors similar to atherosclerosis. As for
      atherosclerosis, infection with Chlamydia (C.) pneumoniae is also discussed as a
      further potential risk factor for calcific aortic stenosis. Previous
      seroepidemiologic and pathologic studies using various detection methods yielded
      heterogeneous results. CONCLUSION: Thus, data suggesting a pathogenetic
      association of C. pneumoniae and calcific aortic stenosis should be interpreted
      cautiously.

PMID- 15968486
TI  - [To what extent are recommendations of guidelines relevant in everyday practice?
      An essential question for evaluation studies].
AB  - PURPOSE: To what extent are recommendations of guidelines relevant in everyday
      practice? METHODS: 142 general practitioners (GPs) participating in ten different
      quality circles administered by the statutory medical association of Hesse were
      interviewed by questionnaire, which of 135 recommendations selected from eight
      guidelines they had used during the last 6 weeks. The guidelines proposed
      recommendations for eight frequent indications in primary care. The findings were
      presented to 15 authors of the guidelines. The authors were asked to assess each
      recommendation as essential, important or nonessential to therapy. RESULTS: By
      setting a benchmark of 75% for adherence to each recommendation, 50% of all
      recommendations had been used by the GPs. With very few exceptions the authors of
      the guidelines assessed these recommendations as essential or important to
      therapy. On the other hand, many recommendations that missed the benchmark were
      assessed as nonessential by the authors. CONCLUSION: Recommendations of
      guidelines should be systematically assessed by users and authors together to
      find out which of them are really of clinical relevance.

PMID- 15968487
TI  - [Calcium antagonists: first choice antihypertensive drugs].

PMID- 15968488
TI  - [Abbreviated guidelines for prevention, diagnostics, and therapy of nosocomial
      pneumonia].
AB  - BACKGROUND: Nosocomial pneumonia is a frequent nosocomial infection and the most
      common one in the intensive care unit. Nosocomial pneumonia is associated with a
      significant morbidity and mortality and therefore the outcome of patients with
      this complication becomes worse. Nosocomial infections are within the
      responsibility of predominantly the treating hospital after introduction of the
      DRGs also into the German health care system, and the occurrence of a nosocomial
      infection can also substantially stress the hospital budget. PURPOSE: Prevention,
      diagnosis and a severity-guided therapeutic approach are therefore inevitable
      parts of infectious concepts within the hospital. This abbreviated version of the
      German recommendations for prevention, diagnosis, and therapy of nosocomial
      pneumonia therefore aims at a larger readership and provides clinical pathways
      and worksheets to further improve health care and documentation of nosocomial
      pneumonia.

PMID- 15968489
TI  - [Brugada syndrome, a rare cause of syncope].
AB  - BACKGROUND: The Brugada syndrome is an autosomal dominant disorder characterized
      by life-threatening ventricular tachyarrhythmias due to cardiac conductance
      disturbance without structural heart disease. Mutations of the SCN5A gene cause
      either a reduction in cardiac Na(+) channel expression or alterations in channel
      gating properties, leading to a reduction in Na(+) current amplitude. CASE
      REPORT: A 37-year-old patient presented after a syncopal spell preceded by
      dizziness. 6 years ago he had experienced similar symptoms. At that time,
      physical and clinical examination did not lead to a convincing diagnosis. The
      initial ECG showed typical signs of the Brugada syndrome with descending ST
      elevation in leads V(1) and V(2). The ECG changes could be observed over the next
      3 days. Thereafter, ECG changes reversed to normal. Ultrasound examination did
      not show any signs of structural heart disease. During electrophysiological
      testing no sustained ventricular tachyarrhythmias were inducible. Molecular
      genetic analysis in this young patient revealed a mutation in the SCN5A gene.
      According to the patient's symptoms, an automatic cardioverter defibrillator
      (ICD) was implanted. CONCLUSION: A history of unexplained syncope in patients
      with a structurally normal heart should raise the suspicion of malignant
      arrythmias caused by primary arrythmogenic disorders. The diagnosis of Brugada
      syndrome can be concluded from typical ECG changes (i. e., incomplete right
      bundle branch block, ST elevation in leads V(1)-V(3)) accompanied by typical
      symptoms and a positive family history. To date, there is no effective therapy of
      the gene defect or its pathophysiological correlate available. Therefore, ICD
      therapy is recommended in symptomatic patients to prevent sudden cardiac death.

PMID- 15968490
TI  - [Financial settlement relevant regulation in transfer of patients].

PMID- 15968491
TI  - Ruptured hepatic artery aneurysm: case report and review of literature.
AB  - Herein, we report the case of a 52-year-old female with new-onset right upper
      quadrant pain and hypertension. She was found to have hemoperitoneum upon
      surgical exploration. Visceral angiography demonstrated a left hepatic artery
      aneurysm and an occluded right renal artery. The patient was treated with
      percutaneous angiographic embolization of the left hepatic artery, followed by
      right nephrectomy and cholecystectomy. Ruptured hepatic aneurysms are associated
      with a high mortality rate. The clinical presentation of patients with hepatic
      artery aneurysms is discussed. Early diagnosis and treatment are essential for a
      favorable outcome.

PMID- 15968492
TI  - Renal cell carcinoma associated with tumor thrombus in the inferior vena cava:
      surgical strategies.
AB  - The purpose of this study was to evaluate strategies used for surgical management
      of renal cell carcinoma with a tumoral thrombus extension in the inferior vena
      cava (IVC). From January 2000 to December 2001, urological and vascular surgeons
      jointly undertook surgical treatment on 10 patients with renal cell carcinoma and
      tumor thrombus in the IVC. There were five women and five men, with a mean age of
      60.2 years. The limit of thrombus extension, classified according to the Neves
      and Zincke system, was level I (renal) in one patient, level II (infrahepatic) in
      one, level III (retrohepatic) in three, and level IV (atrial) in five. Exposure
      was achieved by chevron bilateral subcostal laparotomy associated with sternotomy
      in three patients, bilateral subcostal laparotomy in six, and median
      sternolaparotomy in one. Radical nephrectomy associated with caval thrombectomy
      was performed in all patients. Cardiopulmonary bypass was used in four of the
      five level IV patients. The fifth patient was contraindicated for cardiopulmonary
      bypass. Transesophageal echography (TEE)-guided endoluminal occlusion of the
      unobstructed infradiaphragmatic IVC was performed in patients with level III
      thrombus. Clamping of the IVC was performed in patients with levels I and II
      thrombus. All procedures were assisted by continuous TEE surveillance. No
      intraoperative gas or tumor emboli were detected by TEE. The mean number of red
      blood cell units transfused during the course of hospitalization was 9.7 (range 2
      22, median 9). One patient died of multiple organ failure on the day 28 after the
      procedure. The mean duration of hospitalization was 16 days. The mean duration of
      follow-up was 9.7 months. During follow-up, two of the remaining nine patients
      died due to tumor recurrence. Tumor recurrence was also detected in one of the
      seven surviving patients. Surgery for renal cell carcinoma with tumor thrombus in
      the IVC must be carried out in a specialized facility with the assistance of TEE
      surveillance and, in some cases, cardiopulmonary bypass. Operative treatment
      improves the prognosis of renal cell carcinoma with tumor thrombus in the IVC. In
      patients with level III thrombus, TEE-guided endoluminal occlusion of the
      unobstructed infradiaphragmatic IVC simplifies surgical management by obviating
      the need for exposure of the retrohepatic and supradiaphragmatic IVC.

PMID- 15968493
TI  - Hyperperfusion syndrome after carotid endarterectomy.
AB  - The hyperperfusion syndrome is a rare delayed postoperative complication of
      carotid endarterectomy (CEA) characterized by headache and seizure, with or
      without intracranial edema or hemorrhage. Between January 1996 and December 2003,
      1,602 CEAs were performed. Six patients (0.4%) developed symptoms of
      hyperperfusion within 2 weeks of surgery. All patients had critical stenoses,
      five > or =90% and one 80-90%, with poor backbleeding from the distal internal
      carotid artery noted at operation in all cases. Five patients were asymptomatic
      prior to operation; one had a hemispheric transient ischemic attack. Three
      patients had severe contralateral internal carotid disease (two occlusions and
      one severe stenosis). Two patients developed severe, self-limiting headache that
      prolonged hospitalization. Three patients had ipsilateral intracranial bleeding,
      two occurring after an uneventful postoperative course. After initial discharge
      from the hospital, severe intracranial hemorrhage caused death in two patients.
      One patient experienced focal seizures 1 week after discharge. Hypertension did
      not appear to be related to the symptoms in any case. During the study period,
      the hyperperfusion syndrome caused three of five perioperative strokes (60%) and
      two of seven deaths (29%) in the entire endarterectomy population. Although rare,
      the hyperperfusion syndrome accounts for a significant percentage of the
      neurological morbidity and mortality following CEA.

PMID- 15968494
TI  - Aortic neck attachment failure and the AneuRx graft: incidence, treatment
      options, and early results.
AB  - Some investigators have reported that proximal attachment failure is a long-term
      complication of endovascular abdominal aortic aneurysm repair (EVAR) with the
      AneuRx (Medtronic, Santa Rosa, CA) device. We evaluated the need for an
      intervention in patients with suboptimal proximal fixation as well as the
      feasibility and early success of a variety of treatment strategies. From October
      1999 to October 2003, we performed 365 EVARs using the AneuRx graft. At a mean
      follow-up of 23.7 +/- 14.8 months, 20 patients (5.5%) with suboptimal outcomes
      (14 with a type I endoleak, one with a type III endoleak, and 5 with an
      inadequate seal zone <1 cm) were considered for treatment. Characteristics of
      each patient''s aortic neck anatomy that could be associated with proximal
      attachment failure were evaluated. Eighteen patients (90%) underwent successful
      treatment (9 AneuRx cuffs, 6 Talent cuffs, 5 aortic stents, one redo endograft,
      and two surgical conversions) without major perioperative complications, one
      patient had a persistent type I endoleak despite endovascular treatment, and one
      patient refused treatment, ultimately leading to aneurysm rupture. There have
      been no further endoleaks or graft migrations noted since the secondary
      intervention at a mean follow-up of 13.9 +/- 11.8 months. In our experience,
      proximal attachment failure associated with the AneuRx graft is relatively
      uncommon and usually associated with unfavorable neck anatomy. Despite this, most
      cases are treatable by endovascular means. Long-term follow-up is needed to
      assess the ultimate frequency of these combined device reconstructions.

PMID- 15968495
TI  - Surgical treatment for prostate cancer in patients with prior spinal cord injury.
AB  - BACKGROUND: Limited published information is available concerning the clinical
      course of spinal cord-injured (SCI) patients who develop prostate carcinoma and
      subsequently undergo radical surgery. We hypothesized that the choice of surgical
      treatment and the technical conduct of radical surgery would be influenced by
      sequelae of SCI and that poorer outcomes would result in this population as
      compared with neurally intact patients. METHODS: A nationwide study was conducted
      of all SCI veterans receiving care at Department of Veterans Affairs Medical
      Centers who subsequently developed prostate carcinoma and underwent curative
      intent radical operations between 1993 and 2002. Only patients with complete SCI
      due to trauma who met American Spinal Injury Association type A criteria were
      analyzed. The unpaired t-test was used to analyze data. RESULTS: Of 16,878
      patients who underwent radical operations for prostate cancer, 55 had preexisting
      diagnostic codes for SCI. After record review, 14 met all inclusion criteria. The
      mean age was 57 years. All were asymptomatic with clinically organ-confined
      disease diagnosed by an increased prostate-specific antigen level or abnormal
      digital rectal examination results. Comorbid conditions were present in 9 (69%)
      of 13 patients. Twelve underwent radical prostatectomy, and two underwent
      cystoprostatectomy. There were no operative deaths, but 8 (57%) of 14 had
      complications (P < .05). The mean length of stay (16 days) was significantly
      longer (P < .05) than in neurally intact patients. CONCLUSIONS: SCI patients
      tended to be younger than neurally intact patients with prostate cancer, and the
      rate of cystoprostatectomy was high. The complication rate was significantly
      higher and the hospital stay was significantly longer than in neurally intact
      patients.

PMID- 15968496
TI  - Predicting biopsy outcome after mammography: what is the likelihood the patient
      has invasive or in situ breast cancer?
AB  - BACKGROUND: As many as 1,000,000 breast biopsies are performed annually in the
      United States. Although substantial effort has been devoted to estimating breast
      cancer risk, there have been no studies to predict outcome in women undergoing
      breast biopsy. METHODS: A population-based study was undertaken to develop and
      test models for predicting the probability of invasive breast cancer and/or
      ductal carcinoma-in-situ in 7670 women undergoing breast biopsy after
      mammography. Logistical prediction models were developed by using data from 6129
      randomly selected women and tested with data from the remaining women. RESULTS:
      The overall cancer prevalence among women undergoing biopsy was 22.4%. Prevalence
      in women with mammograms highly suggestive of malignancy (category 5) was 84.6%,
      with minimal variation in individual cancer probabilities due to age. A total of
      24.6% of women with suspicious mammograms (category 4) had cancer, but individual
      probability estimates ranged from .01 to .86, depending on age, presence of a
      lump, previous biopsy, menopausal status, and use of postmenopausal hormone
      therapy. These variables also influenced biopsy outcome in women with other
      mammography assessments (categories 0-3), but the overall prevalence was lower
      (8.6%), and estimated probabilities ranged from .01 to .45. When cancer was
      present, the probability of invasive disease was influenced by mammogram
      assessment category, absence of mammogram calcifications, and presence of a lump.
      CONCLUSIONS: The probabilities of invasive cancer and ductal carcinoma-in-situ in
      women undergoing biopsy can be more accurately predicted by using clinical
      characteristics in addition to mammography findings. This information could
      potentially influence decisions regarding immediate biopsy or continued
      surveillance.

PMID- 15968497
TI  - Feasibility and efficacy of combination therapy with preoperative and
      postoperative chemoradiation, extended pancreatectomy, and postoperative liver
      perfusion chemotherapy for locally advanced cancers of the pancreatic head.
AB  - BACKGROUND: The outcome after resection of advanced pancreatic cancers is
      extremely poor because of the high incidence of the postoperative development of
      liver metastasis and local recurrence. We performed a combination of
      chemoradiation and liver perfusion chemotherapy and extended pancreatectomy.
      METHODS: Nineteen patients with T3 pancreatic head cancers were enrolled. A total
      of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion
      of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head
      area. An extended pancreaticoduodenectomy was performed, and catheters were
      placed into the gastroduodenal artery and the superior mesenteric vein. During
      the first 28 postoperative days, 5-FU was continuously infused via the hepatic
      artery and portal vein (3.5 g/28 days x 2). Finally, 36 Gy in 18 fractions with 5
      FU (3 g/6 days) was applied to the pancreatic bed. RESULTS: After preoperative
      chemoradiation, four patients did not undergo surgical resection because of
      distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver
      perfusion chemotherapy, and postoperative chemoradiation. No patient developed
      grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%)
      developed grade 3 leukopenia during the postoperative treatments. The morbidity
      rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3
      year survival rate was 53%. The 3-year disease-free survival rate was 66% in
      patients who pathologically responded well (>50%), versus 0% in patients with
      poor responses (P = .04). CONCLUSIONS: A combination of preoperative and
      postoperative chemoradiation plus postoperative liver perfusion chemotherapy with
      an extended pancreatectomy is feasible, and the long-term outcomes are also
      promising.

PMID- 15968498
TI  - Efficacy of repeat isolated limb perfusions with tumor necrosis factor alpha and
      melphalan for multiple in-transit metastases in patients with prior isolated limb
      perfusion failure.
AB  - BACKGROUND: Isolated limb perfusion (ILP) is an effective treatment modality for
      multiple in-transit melanoma metastases confined to the limb. Recurrences after
      ILP, however, occur in approximately 50% of patients and are a challenge for
      further treatment. The efficacy of repeat ILPs to prolong local control in this
      patient category is evaluated in this article. METHODS: We used a prospective
      database in a tertiary referral center. Out of 100 tumor necrosis factor (TNF)
      based ILPs with TNF and melphalan (TM-ILPs) in melanoma patients between March
      1991 and July 2003, 25 repeat ILP procedures were performed in 21 patients in
      whom prior ILP treatment failed. All patients had bulky and/or numerous lesions
      and were treated with mild hyperthermic TM-ILP by using 2 to 4 mg of TNF and 10
      to 13 mg/L of limb volume for the leg and arm, respectively. RESULTS: The
      complete response rate was 76%, a partial response occurred in 20%, and no change
      was recorded in 4%. There was no difference in the complete response rate or
      local toxicity between first and repeat perfusions. Local recurrence occurred in
      72%; the median time to local progression was 14 months. The 5-year survival rate
      was 47%, which compares favorably with known survival rates of stage IIIA/AB
      patients. The median follow-up of the patients was 26 months. CONCLUSIONS:
      Patients who experience treatment failure after previous ILP treatment respond
      very well to repeat perfusion, and prolonged local control can thus be obtained.
      The subgroup of patients qualifying for repeat ILP represents a relatively
      favorable biological behavior of the melanoma.

PMID- 15968499
TI  - Diversity of conidia of aquatic hyphomycetes assessed by microscopy and by DGGE.
AB  - Water samples from a Canadian stream were passed through membrane filters between
      22 July 2002 and 19 May 2003. Filters with trapped conidia of aquatic
      hyphomycetes were cut in half. One half was examined under a light microscope,
      and conidia were counted and identified. From the second half, DNA was extracted
      and amplified with fungal primers. The number of different ITS sequences
      (phylotypes) in the amplified DNA was assessed with DGGE. On average, the number
      of visually identified species per sample (12.4) was higher than the number of
      phylotypes (11.7), but the difference was nonsignificant (P = 0.36). However, the
      difference between species and phylotype numbers increased significantly with the
      number of species or conidia present on the filter, indicating that the
      sensitivity of DGGE decreases with sample size. When few conidia were present,
      phylotype numbers often exceeded species numbers, suggesting insufficient
      resolution of visual identification or the presence of DNA from nonconidial
      sources. A modification of the described method may be useful to check the
      accuracy of taxonomy and identification based on conidial morphology.

PMID- 15968500
TI  - Biological and molecular variability of Sarocladium oryzae, the sheath rot
      pathogen of rice (Oryza sativa L.).
AB  - Sheath rot disease of rice caused by Sarocladium oryzae (Sawada) (=Acrocylindrium
      oryzae, Sawada) has become an important production constraint in all rice-growing
      countries. Pathogenicity, phytotoxic metabolites, and random amplified
      polymorphic DNA (RAPD) markers were used to assess the level of genetic
      variability of S. oryzae derived from rice cultivars, CR1018, IR36, and IR50, of
      different locations in North East and South India. Variability in pathogenicity,
      phytotoxic metabolite production, and DNA polymorphisms was detected among S.
      oryzae isolates. Results indicated that S. oryzae isolates produced both
      cerulenin and helvolic acid at concentrations 0.3-0.62 and 0.9-4.8 microg mL(-1)
      of culture filtrate, respectively. Isolates that produce higher concentration of
      helvolic acid induced a high percent incidence of sheath rot disease.
      Oligonucleotide primers, GF and MR, generated either a simple (up to 2 bands) or
      complex (up to 6 bands) RAPD pattern. According to their level of similarity, S.
      oryzae isolates from North East and South India were grouped separately into two
      major clusters and 13 genotypes. Molecular- and pathogenicity-based
      classifications were not correlated, but a high level of genetic variability
      within S. oryzae isolates was identified. The molecular variability of S. oryzae
      isolates will be an important consideration in breeding programs to develop
      durable resistance for sheath rot disease.

PMID- 15968501
TI  - Genetic characterization of the poly(hydroxyalkanoate) synthases of various
      Pseudomonas oleovorans strains.
AB  - We identified the poly(hydroxyalkanoate) synthase (PHAS) genes of three strains
      of Pseudomonas oleovorans by using polymerase chain reaction (PCR)-based
      detection methods. P. oleovorans NRRL B-14682 contains Class I PHA synthase gene
      (phaC), NRRL B-14683 harbors Class II phaC1 and phaC2 genes, and NRRL B-778
      contain both the Class I and II PHA synthase genes. Inverse-PCR and chromosomal
      walking techniques were employed to obtain the complete sequences of the Class I
      phaCs of NRRL B-778 (phbC778; 1698 bps) and B-14682 (phbC14682; 1899 bps). BLAST
      search indicated that these genes are new and had not been previously cloned. The
      gene product of phbC778 (i.e., PhbC778; 566 amino acid residues) is homologous to
      the Class I PHA synthases of Pseudomonas sp. HJ-2 and Pseudomonas sp. strain 61
      3, and that of phbC14682 (PhbC14682; 632 amino acids) is homologous to PHAS of
      Delftia acidovorans. The PhbC14682 contains an extra sequence of 33 amino acids
      in its conserved alpha/beta-hydrolase domain, making it only the second Class I
      PHA synthase found to contain this cellular proteolytic sequence. Consistent with
      their Pseudomonas origin, the codon-usage profiles of PhbC778 and PhbC14682 are
      similar to those of Pseudomonas Class II PHASs. These new Pseudomonas Class I
      phbC genes provide valuable addition to the gene pool for the construction of
      novel PHASs through gene shuffling.

PMID- 15968502
TI  - Expression of inducible nitric oxide synthase mRNA and nitric oxide production
      during the development of liver abscess in hamster inoculated with Entamoeba
      histolytica.
AB  - The present study analyzed iNOS and eNOS mRNA expression and NO production during
      development of hepatic abscess caused by Entamoeba histolytica trophozoites. One
      374-bp sequence, which displayed 88% identity to mammalian iNOS protein, was
      isolated from LPS-stimulated peritoneal hamster macrophages. A separate 365-bp
      cDNA sequence showed 99% identity with eNOS protein. iNOS mRNA was detected in
      hamsters during formation of amoebic liver abscesses, but not in control
      hamsters. eNOS mRNA expression was not modified. Serum nitrite concentration in
      hamsters infected with E. histolytica was 33 +/- 6 microM, in control hamsters
      was 20 +/- 3 microM. The study shows that iNOS mRNA expression and NO production
      are induced by E. histolytica trophozoites during amoebic liver abscess
      formation. However, in spite of iNOS mRNA expression and NO production, E.
      histolytica trophozoites induced liver abscess formation in hamster.

PMID- 15968503
TI  - RpoS-mediated growth-dependent expression of the Escherichia coli tkt genes
      encoding transketolases isoenzymes.
AB  - Escherichia coli tktA and tktB genes encode two transketolase isoenzymes involved
      in the pentose-phosphate pathway, In this study, two reporter lacZ fusions, tktA-
      and tktB-lacZ, were constructed to examine their transcriptional regulation on
      the E. coli chromosome. The tktA gene was induced in the exponential growth phase
      and suppressed in the stationary growth phase. However, the genetic elimination
      of the rpoS, whose product is an alternative sigma factor (RpoS), derepressed the
      tktA gene expression in the stationary growth phase, indicating that the RpoS
      sigma factor negatively regulates the tktA gene expression in the stationary
      growth phase. On the contrary, the tktB gene expression showed the highest value
      in the stationary growth phase and the RpoS positively regulated the tktB gene
      expression in the stationary growth phase. We also verified the role of the RpoS
      affecting the regulation of the tktA and tktB gene expression by the reverse
      transcription (RT)-PCR experiments. These results suggest that the differential
      growth-dependent expressions of the tktA and tktB genes are caused by the RpoS
      action.

PMID- 15968504
TI  - Functional expression of bacterial Zymobacter palmae pyruvate decarboxylase gene
      in Lactococcus lactis.
AB  - A pyruvate decarboxylase (PDC) gene from bacterial Zymobacter palmae (Zymopdc)
      was cloned, characterized, and introduced into Lactococcus lactis via a shuttle
      vector pAK80 as part of a research strategy to develop an efficient ethanol
      producing lactic acid bacteria (LAB). The expression levels of Zymopdc gene in
      the host, as measured by a colorimetric assay based on PDC catalyzed formation of
      (R)-phenylacetylcarbinol ((R)-PAC), appeared to be dependent on the strength of
      corresponding Gram-positive promoters. A constitutive, highly expressed promoter
      conferred the greatest PDC activity, and an acid-inducible promoter demonstrated
      acid-inducible expression. The metabolic production of ethanol and other products
      was examined in flask fermentations. More than eightfold increases in
      acetaldehyde concentrations were detected in two recombinant strains. However, no
      detectable differences for ethanol fermentation in these engineered strains were
      observed compared with that of the strain carrying lacZ reporter.

PMID- 15968505
TI  - Analyses of Pseudomonas aeruginosa lectin binding to alpha-galactosylated
      glycans.
AB  - The specificity and binding capacity of the galactophilic lectin from the Gram
      negative bacterium Pseudomonas aeruginosa (PA-IL) was determined by solid phase
      measurements using galactosylated neoglycoproteins immobilized on microtiter
      plates. The bacterial lectin reacted with both short chain (monosaccharide) and
      long chain (pentasaccharide) glycoconjugates. Among the Galalpha1-XGal
      disaccharides, the highest affinity was observed towards the Galalpha1-3Gal
      structure. Raising the incubation temperature enhanced the lectin-polysaccharide
      agglutination, and it is suggested that binding to certain conformations of
      polysaccharides could vary between lectins with the same monocarbohydrate
      specificity and that this activity may, in part, be temperature dependent.
      Histochemical examination of lectin binding to different porcine tissues suggests
      a differential glycosylation of the carbohydrate antigens on endothelial cells in
      various parts of the vascular system. In the pancreas, PA-IL also adhered to the
      excretory ducts. These observations on PA-IL binding could be of importance both
      to determine infection foci in P. aeruginosa-mediated vacuities and to determine
      its role for pancreatic involvement in cystic fibrosis.

PMID- 15968506
TI  - Physiological regulation, xenobiotic induction, and heterologous expression of
      P450 monooxygenase gene pc-3 (CYP63A3), a new member of the CYP63 gene cluster in
      the white-rot fungus Phanerochaete chrysosporium.
AB  - In order to characterize the functional diversity in CYP63 cluster of tandemly
      linked P450 genes (pc-1, pc-2, and pc-3) in Phanerochaete chrysosporium, here we
      report the functional characterization of pc-3 (CYP63A3), a newly cloned member
      of this group. pc-3 expression was favored in nutrient-limited versus nutrient
      rich media in 3-6-day-old cultures and was upregulated by starch as a carbon
      source or by oxygenation of cultures. pc-3 was induced by various xenobiotics in
      defined nutrient-limited (3-9-fold) and nutrient-rich (2-5-fold) cultures.
      Particularly, a range of unsubstituted and substituted aliphatic hydrocarbons
      (alkanes and fatty acids) induced the expression under the two nutrient
      conditions albeit in a differential manner. Interestingly, pc-3 was also
      inducible by certain oxygenated mono aromatics (nitrophenol, benzoate, and
      resorcinol), lower molecular weight (2 to 4 ring size) polycyclic aromatic
      hydrocarbons (PAHs) and alkali-treated lignin derivatives in nutrient-rich malt
      extract cultures. The study further establishes that the three CYP63 genes
      (CYP63A1, A2, and A3) are independently regulated despite being members of the
      tandem gene cluster with high gene structural similarity (13-14 introns) and
      protein sequence homology (59-85%). The pc-3 cDNA (1,812 bp) was expressed in E.
      coli as a His-tagged protein (approximately 74 kDa). This constitutes the first
      report on heterologous expression of a P450 monooxygenase enzyme from this model
      white-rot fungus.

PMID- 15968507
TI  - The Brachyspira hyodysenteriae ftnA gene: DNA vaccination and real-time PCR
      quantification of bacteria in a mouse model of disease.
AB  - The nucleotide sequence of the Brachyspira hyodysenteriae ftnA gene, encoding a
      putative ferritin protein (FtnA), was determined. Analysis of the sequence
      predicted that this gene encoded a protein of 180 amino acids. RT-PCR and Western
      blot showed that the ftnA gene was expressed in B. hyodysenteriae, and evidence
      suggests that FtnA stores iron rather than haem. ftnA was delivered as DNA and
      recombinant protein vaccines in a mouse model of B. hyodysenteriae infection.
      Vaccine efficacy was monitored by caecal pathology and quantification of B.
      hyodysenteriae numbers in the caeca of infected mice by real-time PCR.

PMID- 15968508
TI  - EST sequencing and time course microarray hybridizations identify more than 700
      Medicago truncatula genes with developmental expression regulation in flowers and
      pods.
AB  - To evaluate the molecular mechanisms during pod and seed formation in legumes,
      starting with the development of reproductive organs, we constructed two cDNA
      libraries from developing flowers (MtFLOW) and pods including seeds (MtPOSE) of
      the model plant Medicago truncatula Gaertner. A total of 2,516 expressed sequence
      tags (ESTs) clustered into 1,776 nonredundant sequences (2k-set), which were
      annotated and assigned to functional classes. While about 30% of the ESTs encoded
      proteins of yet unknown function, typical annotations pointed to seed storage
      proteins, LTPs and lipoxygenases. The 2k-set was used to upgrade Mt6k-RIT
      microarrays (Kuster et al. in J Biotechnol 108: 95, 2004) to Mt8k versions
      representing approximately 6,300 nonredundant M. truncatula genes. These were
      used to perform time course expression profiling studies based on hybridizations
      of samples that covered eight different developmental stages from flower buds to
      almost mature pods versus leaves as a common reference. About 180 up- and 70
      downregulated genes were typically found for each stage and in total, 782 genes
      were either twofold up- or downregulated in at least one of the eight stages
      investigated. Based on this set, a combination of self-organizing map and
      hierarchical clustering revealed genes displaying expression regulation during
      characteristic stages of M. truncatula flower and pod development. Amongst those,
      several genes encoded proteins related to seed metabolism and development
      including novel regulators and proteins involved in signaling.

PMID- 15968509
TI  - Lignification in the flax stem: evidence for an unusual lignin in bast fibers.
AB  - In the context of our research on cell wall formation and maturation in flax
      (Linum usitatissimum L) bast fibers, we (1) confirmed the presence of lignin in
      bast fibers and (2) quantified and characterized the chemical nature of this
      lignin at two developmental stages. Histochemical methods (Weisner and Maule
      reagents and KMnO(4)-staining) indicating the presence of lignin in bast fibers
      at the light and electron microscope levels were confirmed by chemical analyses
      (acetyl bromide). In general, the lignin content in flax bast fibers varied
      between 1.5% and 4.2% of the dry cell wall residues (CWRs) as compared to values
      varying between 23.7% and 31.4% in flax xylem tissues. Immunological and chemical
      analyses (thioacidolysis and nitrobenzene oxidation) indicated that both flax
      xylem- and bast fiber-lignins were rich in guaiacyl (G) units with S/G values
      inferior to 0.5. In bast fibers, the highly sensitive immunological probes
      allowed the detection of condensed guaiacyl-type (G) lignins in the middle
      lamella, cell wall junctions, and in the S1 layer of the secondary wall. In
      addition, lower quantities of mixed guaiacyl-syringyl (GS) lignins could be
      detected throughout the secondary cell wall. Chemical analyses suggested that
      flax bast-fiber lignin is more condensed than the corresponding xylem lignin. In
      addition, H units represented up to 25% of the monomers released from bast-fiber
      lignin as opposed to a value of 1% for the corresponding xylem tissue. Such an
      observation indicates that the structure of flax bast-fiber lignin is
      significantly different from that of the more typical 'woody plant lignin',
      thereby suggesting that flax bast fibers represent an interesting system for
      studying an unusual lignification process.

PMID- 15968510
TI  - Rice SERK1 gene positively regulates somatic embryogenesis of cultured cell and
      host defense response against fungal infection.
AB  - Here we report on the isolation and characterization of a somatic embryogenesis
      receptor-like kinase (OsSERK1) gene in rice (Oryza sativa). The OsSERK1 gene
      belongs to a small subfamily of receptor-like kinase genes in rice and shares a
      highly conserved gene structure and extensive sequence homology with previously
      reported plant SERK genes. Though it has a basal level of expression in various
      rice organs/tissues, as high expression level was detected in rice callus during
      somatic embryogenesis. Suppression of OsSERK1 expression in transgenic calli by
      RNA interference resulted in a significant reduction of shoot regeneration rate
      (from 72% to 14% in the japonica rice Zhonghua11). Overexpression of OsSERK1,
      however, increased the shoot regeneration rate (from 72% to 86%). Interestingly,
      OsSERK1 is significantly activated by the rice blast fungus, particularly during
      the incompatible interaction, and is associated with host cell death in Sekigushi
      lesion mimic mutants. This gene is also inducible by defense signaling molecules
      such as salicylic acid, jasmonic acid, and abscisic acid. Furthermore,
      constitutive overexpression of OsSERK1 in two rice cultivars led to an increase
      in host resistance to the blast fungus. Our data suggest that OsSERK1 may
      partially mediate defense signal transduction in addition to its basic role in
      somatic embryogenesis.

PMID- 15968511
TI  - Microgravity does not alter plant stand gas exchange of wheat at moderate light
      levels and saturating CO2 concentration.
AB  - Plant stand gas exchange was measured nondestructively in microgravity during the
      Photosynthesis Experiment Subsystem Testing and Operations experiment conducted
      onboard the International Space Station. Rates of evapotranspiration and
      photosynthesis measured in space were compared with ground controls to determine
      if microgravity directly affects whole-stand gas exchange of Triticum aestivum.
      During six 21-day experiment cycles, evapotranspiration was determined
      continuously from water addition rates to the nutrient delivery system, and
      photosynthesis was determined from the amount of CO2 added to maintain the
      chamber CO2 concentration setpoint. Plant stand evapotranspiration, net
      photosynthesis, and water use efficiency were not altered by microgravity.
      Although leaf area was significantly reduced in microgravity-grown plants
      compared to ground control plants, leaf area distribution was not affected enough
      to cause significant differences in the amounts of light absorbed by the flight
      and ground control plant stands. Microgravity also did not affect the response of
      evapotranspiration to changes in chamber vapor pressure difference of 12-day-old
      wheat plant stands. These results suggest that gravity naive plants grown at
      moderate light levels (300 micromol m(-2) s(-1)) behave the same as ground
      control plants. This implies that future plant-based regenerative life support
      systems can be sized using 1 g data because water purification and food
      production rates operate at nearly the same rates as in 1 g at moderate light
      levels. However, it remains to be verified whether the present results are
      reproducible in plants grown under stronger light levels.

PMID- 15968512
TI  - Characterization of the monophenolase activity of tyrosinase on betaxanthins: the
      tyramine-betaxanthin/dopamine-betaxanthin pair.
AB  - Tyrosinase or polyphenol oxidase (EC 1.14.18.1) is the key enzyme responsible for
      melanin biosynthesis and for the enzymatic browning of fruits and vegetables.
      Although the function of tyrosinase in the secondary metabolism of plants remains
      unclear, it has been proposed that the enzyme plays a role in the betalain
      biosynthetic pathway. Betalains are an important class of water-soluble pigments,
      characteristic of plants belonging to the order Caryophyllales. In the present
      work, the betaxanthins tyramine-betaxanthin (miraxanthin III) and dopamine
      betaxanthin (miraxanthin V) are reported as new natural substrates for
      tyrosinase. The result of the diphenolase activity of the enzyme on dopamine
      betaxanthin was a series of products identified by HPLC and ESI-MS as quinone
      derivatives. Data indicate that dopamine-betaxanthin-quinone is obtained and
      evolves to more stable species by intramolecular cyclization. The kinetic
      parameters evaluated for the diphenolase activity were V(m) = 74.4 microM min(
      1), K(m) = 94.7 microM. Monophenolase activity on tyramine-betaxanthin yielded
      the same compounds in the absence of a reducing agent, but when ascorbic acid was
      present enzymatic conversion to dopamine-betaxanthin could be found. For the
      first time, kinetic characterization of the monophenolase activity of tyrosinase
      on betaxanthins is provided (V(m) = 10.4 microM min(-1) and K(m) = 126.9 microM)
      and a lag period is described and analyzed according to the mechanism of action
      of the enzyme. The high affinity shown by tyrosinase for these substrates may be
      indicative of a previously unconsidered physiological role in betalain
      metabolism. A possible mechanism for the formation of 2-descarboxy-betacyanins
      from tyramine-betaxanthin by tyrosinase is also discussed.

PMID- 15968513
TI  - DNA methylation increases throughout Arabidopsis development.
AB  - We used amplified fragment length polymorphisms (AFLP) to analyze the stability
      of DNA methylation throughout Arabidopsis development. AFLP can detect genome
      wide changes in cytosine methylation produced by DNA demethylation agents, such
      as 5-azacytidine, or specific mutations at the DDM1 locus. In both cases,
      cytosine demethylation is associated with a general increase in the presence of
      amplified fragments. Using this approach, we followed DNA methylation at
      methylation sensitive restriction sites throughout Arabidopsis development. The
      results show a progressive DNA methylation trend from cotyledons to vegetative
      organs to reproductive organs.

PMID- 15968514
TI  - The effects of salinity, crassulacean acid metabolism and plant age on the carbon
      isotope composition of Mesembryanthemum crystallinum L., a halophytic C(3)-CAM
      species.
AB  - The carbon isotope composition of the halophyte Mesembryanthemum crystallinum L.
      (Aizoaceae) changes when plants are exposed to environmental stress and when they
      shift from C(3) to crassulacean acid metabolism (CAM). We examined the coupling
      between carbon isotope composition and photosynthetic pathway by subjecting
      plants of different ages to salinity and humidity treatments. Whole shoot
      delta(13)C values became less negative in plants that were exposed to 400 mM NaCl
      in the hydroponic solution. The isotopic change had two components: a direct NaCl
      effect that was greatest in plants still operating in the C(3) mode and decreased
      proportionally with increasing levels of dark fixation, and a second component
      related to the degree of CAM expression. Ignoring the presumably diffusion
      related NaCl effect on carbon isotope ratios results in an overestimation of
      nocturnal CO(2) gain in comparison to an isotope versus nocturnal CO(2) gain
      calibration established previously for C(3) and CAM species grown under well
      watered conditions. It is widely taken for granted that the shift to CAM in M.
      crystallinum is partially under developmental control and that CAM is inevitably
      expressed in mature plants. Plants, cultivated under non-saline conditions and
      high relative humidity (RH) for up to 63 days, maintained diel CO(2) gas-exchange
      patterns and delta(13)C values typical of C(3) plants. However, a weak CAM gas
      exchange pattern and an increase in delta(13)C value were observed in non-salt
      treated plants grown at reduced RH. These observations are consistent with
      environmental control rather than developmental control of the induction of CAM
      in mature M. crystallinum under non-saline conditions.

PMID- 15968515
TI  - The value of drip infusion cholangiography using multidetector-row helical CT in
      patients with choledocholithiasis.
AB  - The purposes of this study were to investigate the feasibility of drip infusion
      cholangiography computed tomography (CTCh) for choledocholithiasis and to compare
      the detection of the stone on CTCh with that of MR cholangiopancreatography
      (MRCP). CTCh examinations were performed after infusion of intravenous biliary
      contrast material (iotroxic acid meglumine, 100 ml) for patients with suspected
      biliary diseases and were reconstructed to maximum intensity projection (MIP) and
      multiplanar reformation (MPR). Of 432 patients who underwent CTCh, we identified
      15 who underwent surgery or cholangioscopic removal for choledocholithiasis and
      32 patients who underwent cholecystectomy due to cholecystolithiasis. Their MRCP
      images were compared with the CTCh images. The sensitivity and specificity of
      CTCh for detecting choledochal stones were 87% and 96% whereas those of MRCP were
      80% and 88%. The sensitivity and specificity of CTCh for detecting gallstones
      were 78% and 100% whereas those of MRCP were 94% and 88%. CTCh allowed high
      sensitivity and specificity for detecting choledochal stones but diminished the
      detection for cholecystolithiasis compared with MRCP.

PMID- 15968516
TI  - Assessment of reproducibility and stability of different breath-hold maneuvres by
      dynamic MRI: comparison between healthy adults and patients with pulmonary
      hypertension.
AB  - To assess the stability and reproducibility of different breath-hold levels in
      healthy volunteers and patients using dynamic MRI (dMRI). In ten healthy
      volunteers and ten patients with pulmonary hypertension (PH) and normal lung
      function craniocaudal intrathoracic distances (CCD) were measured during
      inspiratory and expiratory breath-hold (15 s) (in healthy volunteers additionally
      at a self-chosen mid-inspiratory breath-hold) using dMRI (trueFISP, three
      images/s). To evaluate stability and intraobserver reproducibility of the
      different breath-hold levels, CCDs, time-distance curves, confidence intervals
      (CIs), Mann-Witney U test and regression equations were calculated. In healthy
      volunteers there was a substantial decrease of the CCD during the inspiratory
      breath-hold in contrast to the expiratory breath-hold. The CI at inspiration was
      2.84+/-1.28 in the right and 2.1+/-0.68 in the left hemithorax. At expiration the
      CI was 2.54+/-1.18 and 2.8+/-1.48. Patients were significantly less able to hold
      their breath at inspiration than controls (P<0.05). In patients CI was 4.53+/
      4.06 and 3.46+/-2.21 at inspiration and 4.45+/-4.23 and 4.76+/-3.73 at
      expiration. Intraobserver variability showed no significant differences either in
      patients or in healthy subjects. Reproducibility was significantly lower at a
      self-chosen breath-hold level of the healthy volunteers. DMRI is able to
      differentiate stability and reproducibility of different breath-hold levels.
      Expiratory breath-hold proved to be more stable than inspiratory breath-hold in
      healthy volunteers and patients.

PMID- 15968517
TI  - Low-dose intra-arterial contrast-enhanced MR aortography in patients based on a
      theoretically derived injection protocol.
AB  - Multiple intra-arterial contrast agent injections are necessary during MR-guided
      endovascular interventions. In respect to the approved limits of maximum daily
      gadolinium dose, a low-dose injection protocol is mandatory. The objective of
      this study was to derive and apply a low-dose injection protocol for intra
      arterial 3D contrast-enhanced MR aortography in patients. Injection rate (Qinj),
      concentration of injected gadolinium [Gd]inj and aortal blood flow rate (Qblood)
      were included for the theoretical evaluation of signal intensity (SI) of the
      arterial lumen. SI simulations were carried out at Qinj=2 versus 4 ml/s in the
      [Gd]inj range between 0-500 mM. Qinj and [Gd]inj with SI above the 75% threshold
      of the maximal SI were regarded as optimal injection parameters. [Gd]inj=50 mM
      and Qinj=4 ml/s were considered as optimal and were administered in five patients
      for 3D MR aortography. All images revealed clear delineation of the abdominal
      aorta and its major branches. Mean+/-SD of contrast-to-noise ratios of the
      abdominal aorta, common iliac and renal artery were 70.2+/-15.2, 58.6+/-12.3 and
      67.4+/-12.3. Approximately seven intra-aortal injections would be permissible in
      patients during MR-guided interventions without exceeding the maximal dose of
      gadolinium.

PMID- 15968518
TI  - Evaluation of chronic infectious interstitial pulmonary disease in children by
      low-dose CT-guided transthoracic lung biopsy.
AB  - BACKGROUND: Children with chronic infectious interstitial lung disease often have
      to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy is
      an invasive procedure with major potential complications. Transthoracic lung
      biopsy (TLB) guided by computed tomography (CT) is a less-invasive well
      established procedure in adults. OBJECTIVE: Detailing the role of low-dose CT
      guided TLB in the enhanced diagnosis of chronic lung diseases related to
      infection in children. MATERIALS AND METHODS: A group of 11 children (age 8
      months to 16 years) underwent CT-guided TLB with a 20-gauge biopsy device. All
      investigations were done under general anaesthesia on a multidetector CT scanner
      (SOMATOM Volume Zoom, Siemens, Erlangen, Germany) using a low-dose protocol
      (single slices, 120 kV, 20 mAs). Specimens were processed by histopathological,
      bacteriological, and virological techniques. RESULTS: All biopsies were performed
      without major complications; one child developed a small pneumothorax that
      resolved spontaneously. A diagnosis could be obtained in 10 of the 11 patients.
      Biopsy specimens revealed chronic interstitial alveolitis in ten patients. In
      five patients Chlamydia pneumoniae PCR was positive, in three Mycoplasma
      pneumoniae PCR was positive, and in two Cytomegalovirus PCR was positive. The
      average effective dose was 0.83 mSv. CONCLUSION: Low-dose CT-guided TLB can be a
      helpful tool in investigating chronic infectious inflammatory processes in
      children with minimal radiation exposure. It should be considered prior to any
      open surgical procedure performed for biopsy alone. In our patient group no
      significant complication occurred. A disadvantage of the method is that it does
      not allow smaller airways and vessels to be assessed.

PMID- 15968519
TI  - Imaging the vertebral artery.
AB  - Although conventional intraarterial digital subtraction angiography remains the
      gold standard method for imaging the vertebral artery, noninvasive modalities
      such as ultrasound, multislice computed tomographic angiography and magnetic
      resonance angiography are constantly improving and are playing an increasingly
      important role in diagnosing vertebral artery pathology in clinical practice.
      This paper reviews the current state of vertebral artery imaging from an evidence
      based perspective. Normal anatomy, normal variants and a number of pathological
      entities such as vertebral atherosclerosis, arterial dissection, arteriovenous
      fistula, subclavian steal syndrome and vertebrobasilar dolichoectasia are
      discussed.

PMID- 15968520
TI  - Contrast media: interactions with other drugs and clinical tests.
AB  - Many patients with multiple medical problems who are receiving a variety of drugs
      are investigated with imaging techniques which require intravascular contrast
      media. The Contrast Media Safety Committee of the European Society of Urogenital
      Radiology therefore decided to review the literature and to draw up simple
      guidelines on interactions between contrast media and other drugs. An extensive
      literature search was carried out and summarized in a report. Based on the
      available information, simple guidelines have been drawn up. The report and
      guidelines were discussed at the 11th European Symposium on Urogenital Radiology
      in Santiago de Compostela. Contrast media may interact with other drugs, and may
      interfere with isotope studies and biochemical measurements. Awareness of the
      patient drug history is important to avoid potential hazards. Simple guidelines
      are presented.

PMID- 15968521
TI  - [Options in HIV therapy: present and future].
AB  - Highly active antiretroviral therapy (HAART) has markedly decreased HIV
      associated mortality. It consists of a combination of three antiretroviral drugs
      from four different classes: nucleoside reverse transcriptase inhibitors, non
      nucleoside reverse transcriptase inhibitors, protease inhibitors and inhibitors
      of virus-cell fusion. Increasing resistance against antiretroviral drugs calls
      for the development of new compounds and drug classes. The growing understanding
      of molecular mechanisms in HIV-replication led to the identification of further
      steps which might serve as novel antiretroviral targets. Uninfected cells could
      be protected from HIV by inhibiting extracellular binding mechanisms. Improvement
      of existing antiretroviral drugs and further development of novel therapeutic
      targets will enrich antiretroviral treatment.

PMID- 15968522
TI  - Colonic response to food in constipation.
AB  - OBJECTIVES: Colonic response to food is possibly abnormal in constipation.
      METHODS: The colonic response to food was evaluated in 323 patients and 60
      healthy subjects by following the movements of radiopaque markers after ingestion
      of a standard 1,000-cal test meal. Constipated patients were divided into four
      groups: one with a normal, and three with a delayed colorectal transit time. When
      the delay was found mainly in the ascending colon, the group was labeled as
      suffering from "colonic inertia". In "hindgut dysfunction", the delay was
      predominantly found in the descending colon, whereas the term "outlet
      obstruction" was reserved for constipated patients whose major site of delay was
      the rectosigmoid area. Colonic response to food was quantified by evaluating the
      variation of markers in a given abdominal region and the evolution of the
      geometric center on the entire plain film of the abdomen. RESULTS: Emptying of
      the caecum-ascending colon and filling of the rectosigmoid area characterize the
      colonic response to food in healthy subjects. Constipated patients also filled
      the rectosigmoid, but different patterns were found in the colon. In constipated
      patients with transit in the normal range, there was a frequent (41%) absence of
      colonic response to food as compared to controls (13%) and constipated patients
      with delayed transit (p<0.0001). The response to food of patients with colonic
      inertia was similar to that of healthy subjects in terms of distal progression,
      but less marked. The hindgut dysfunction group emptied the entire left colon but
      failed to empty the caecum and ascending colon. In the outlet obstruction group,
      there was no distal progress of the geometric center after meal. CONCLUSIONS:
      Abnormal colonic response to food is frequently found in constipated patients,
      with different patterns according to the type of constipation.

PMID- 15968523
TI  - Resectability of rectal cancers still fixed after radio-chemotherapy: evaluation
      by digital rectal examination, MRI, and intraoperative examination.
AB  - Eighteen patients with primary fixed rectal cancer as judged by digital rectal
      examination (DRE) were included. They all had radiation therapy with 60 Gy in 30
      fractions combined with oral UFT and Isovorin. All patients were evaluated by DRE
      and magnetic resonance imaging (MRI) before and after treatment. After 5-7 weeks,
      eight tumors were mobile on DRE. All eight patients had an R0 resection. Of the
      remaining ten patients with fixed rectal cancer, eight had an R0 resection. One
      patient had an R1 resection and one patient was not operated. Intraoperative
      bimanual rectal examination was performed with one finger through the anus and
      one hand in the rectovaginal/rectovesical fossa before resection was performed.
      After chemo-radiation DRE correctly predicted the tumor to be advanced or not in
      12/17 patients, MRI in 14/17, and bimanual rectal examination in 17/17 patients.

PMID- 15968524
TI  - Carcinoma of the colon caused intussusception presenting with obstructive ileus.

PMID- 15968525
TI  - Veratrol-O-demethylase of Acetobacterium dehalogenans: ATP-dependent reduction of
      the corrinoid protein.
AB  - The anaerobic veratrol O-demethylase mediates the transfer of the methyl group of
      the phenyl methyl ether veratrol to tetrahydrofolate. The primary methyl group
      acceptor is the cobalt of a corrinoid protein, which has to be in the +1
      oxidation state to bind the methyl group. Due to the negative redox potential of
      the cob(II)/cob(I)alamin couple, autoxidation of the cobalt may accidentally
      occur. In this study, the reduction of the corrinoid to the superreduced [Co(I)]
      state was investigated. The ATP-dependent reduction of the corrinoid protein of
      the veratrol O-demethylase was shown to be dependent on titanium(III) citrate as
      electron donor and on an activating enzyme. In the presence of ATP, activating
      enzyme, and Ti(III), the redox potential versus the standard hydrogen electrode
      (E (SHE)) of the cob(II)alamin/cob(I)alamin couple in the corrinoid protein was
      determined to be -290 mV (pH 7.5), whereas E (SHE) at pH 7.5 was lower than -450
      mV in the absence of either activating enzyme or ATP. ADP, AMP, or GTP could not
      replace ATP in the activation reaction. The ATP analogue adenosine-5'-(beta,gamma
      imido)triphosphate (AMP-PNP, 2-4 mM) completely inhibited the corrinoid reduction
      in the presence of ATP (2 mM).

PMID- 15968526
TI  - Molecular mapping of gibberellin-responsive dwarfing genes in bread wheat.
AB  - Opportunities exist for replacing reduced height (Rht) genes Rht-B1b and Rht-D1b
      with alternative dwarfing genes for bread wheat improvement. In this study, the
      chromosomal locations of several height-reducing genes were determined by
      screening populations of recombinant inbred lines or doubled haploid lines
      varying for plant height with microsatellite markers. Linked markers were found
      for Rht5 (on chromosome 3BS), Rht12 (5AL) and Rht13 (7BS), which accounted for
      most of the phenotypic variance in height in the respective populations. Large
      height differences between genotypes (up to 43 cm) indicated linkage to major
      height-reducing genes. Rht4 was associated with molecular markers on chromosome
      2BL, accounting for up to 30% of the variance in height. Confirming previous
      studies, Rht8 was linked to markers on chromosome 2DS, whereas a population
      varying for Rht9 revealed a region with a small but significant height effect on
      chromosome 5AL. The height-reducing effect of these dwarfing genes was repeatable
      across a range of environments. The molecular markers developed in this study
      will be useful for marker-assisted selection of alternative height-reducing
      genes, and to better understand the effects of different Rht genes on wheat
      growth and agronomic performance.

PMID- 15968527
TI  - Transarticular screw fixation for osteoarthritis of the atlanto axial segment.
AB  - Atlantoaxial (C1-C2) facet joint osteoarthitis is a distinct clinical syndrome
      that often goes unrecognized. Severe pain resistant to conservative treatment
      that is corroborated by the radiographic findings represents the indication for
      surgery. The aim of this study was to retrospectively examine the long-term
      outcome [after an average 6.5 years (SD 4.0)] of C1-2 fusion for osteoarthritis
      of the atlantoaxial segment in 35 consecutive patients [25 male, 10 female; aged
      62 (SD 15) years]. At follow-up, clinical outcome and radiological status was
      examined in 27/35 (77%) patients, and self-rated pain and disability (Neck Pain
      and Disability Scale; NPDS) in 29/35 (83%) patients. In 27/35 patients (77%), 2
      screws were inserted; in 7 patients (20%), only 1 screw; and in 1 patient (3%),
      no screws. 11% of the patients had late complications requiring revision surgery.
      All patients showed solid fusion at the long-term follow-up. 26% patients showed
      an improvement in sensory disturbances, 63% no change, and 11% a worsening. 89%
      were pain-free or had markedly reduced pain. The average score on the NPDS (0
      100) was 34 (SD 27), representing 'mild' neck problems, and the average pain
      intensity (0-5 VAS) was 1.5 (SD 1.5). Eighty-five percent of the patients
      declared that they would make the same decision again to undergo surgery. In
      conclusion, in a group of patients with a painful and debilitating degenerative
      disorder of C1-2, posterior transarticular atlantoaxial fusion proved to be an
      effective treatment with a low rate of serious complications.

PMID- 15968528
TI  - The borders of the odontoid process of C2 in adults and in children including the
      estimation of odontoid/body ratio.
AB  - The odontoid process of C2 projects upward from the superior roof of the body of
      C2. There is a confusion about the inferior border of the odontoid. The aims of
      this clinical study were to describe the inferior border of the odontoid process
      based on the remnant of dentocentral synchondrosis in adults, and the estimation
      of the odontoid/body ratio in pediatric and adult ages. Sixty-six cases were
      included for this study. Forty-four of them were in adult ages and the remaining
      22 of them were in pediatric ages. The region of occiput, C1, C2, and C3, was
      examined with the magnetic resonance imaging (MRI) in all cases. The length of
      the odontoid process was estimated by using radiological images of MR from the
      tip of the odontoid to the remnant of dentocentral synchondrosis. The portion
      located under the level of synchondrosis was considered as the body of C2. The
      average length of the odontoid was 18. 6 mm in pediatric and 21. 3 mm in adult
      cases. In adult females, the length of the odontoid process (19. 1 mm in length)
      was smaller than those of adult males (23. 6 mm in length). The average ratio of
      odontoid/body was two in pediatric and 1.8 in adult cases. This study
      demonstrated that the neck of the odontoid segment at the level of superior
      articulating facets is not the synchondrosis between the odontoid process and the
      body of C2. The synchondrosis is located well below the level of superior
      articulating facets. It can be demonstrated with sagittal and coronal images of
      MR in both of pediatric and adult individuals.

PMID- 15968529
TI  - Transcostovertebral kyphoplasty of the mid and high thoracic spine.
AB  - While Kyphoplasty is increasingly becoming a recognised minimally invasive
      treatment option for osteoporotic vertebral fractures and neoplastic vertebral
      collapse, the experience in the treatment of vertebrae of the mid (T5-8)- and
      high (T1-4) thoracic levels is limited. The slender pedicle morphology restricts
      the transpedicular approach at these levels, necessitating extrapedicular
      placement techniques. Fifty five vertebrae of 32 consecutive patients were
      treated with kyphoplasty at levels ranging from T2-T8 for vertebral fractures (27
      patients) or osteolytic collapse (5 patients). All procedures were performed
      through the transcostovertebral approach under fluoroscopic guidance. The
      radioanatomical landmarks of this minimally invasive approach were consistently
      identified and strictly adhered to. One fracture required open instrumentation
      due to posterior column injury in addition to kyphoplasty. Identification of
      specific radioanatomical landmarks allowed precise tool introduction in all cases
      without intraspinal or paravertebral malplacement. Average operating time for
      patients with osteoporotic fractures was 30 min per level (range 13-60 min) and
      52 min per level (range 35-95 min) in neoplastic cases. Biopsy yield in patients
      with known or suspected malignancies was 100%. Epidural cement leakage was
      detected in one patient with pedicular osteolysis. Perforation of the lateral
      vertebral cortex during balloon inflation occurred in another patient. Both
      intraoperative complications were without clinical significance. Kyphoplasty in
      mid- to -high thoracic levels is possible via the transcostovertebral route under
      fluoroscopic guidance. Strict adherence to a stepwise protocol of tool
      introduction following defined radioanatomical landmarks is mandatory for the
      safe completion of this minimally invasive technique.

PMID- 15968530
TI  - Electromechanical delay of the knee extensor muscles is not altered after
      harvesting the patellar tendon as a graft for ACL reconstruction: implications
      for sports performance.
AB  - Although the scar tissue, which heals the donor site defect, has different
      elasticity from the neighbouring patellar tissue, it remains unclear if this scar
      tissue can lead to the changes of the electromechanical delay (EMD) of the knee
      extensor muscles. If such changes do exist, they can possibly affect both the
      utilization of the stored energy in the series elastic component, as well as the
      optimal performance of the knee joint movement. The purpose of this study was to
      investigate the influence of harvesting the patellar tendon during anterior
      cruciate ligament (ACL) reconstruction and the associated patellar tendon scar
      tissue development on the EMD of the rectus femoris (RF) and vastus medialis (VM)
      muscles. Seventeen patients who underwent an ACL reconstruction using the medial
      third of the patellar tendon were divided in two groups based upon their post
      operative time interval. Maximal voluntary contraction from the knee extensors,
      surface EMG activity, and ultrasonographic measurements of the patellar tendon
      cross-section area were obtained from both knees. Our results revealed that no
      significant changes for the maximal voluntary contraction of the knee extensors
      and for the EMD of the RF and the VM muscles due to patellar scar tissue
      development after harvesting the tendon for ACL reconstruction. The EMD, as a
      component of the stretch reflex, is important for the utilization of the stored
      energy in the series elastic component and thus, optimal sports performance.
      However, from our results, it can be implied that the ACL reconstruction using a
      patellar tendon graft would not impair sports performance as far as EMD is
      concerned.

PMID- 15968531
TI  - Bilateral hypoplasia of the medial meniscus.
AB  - Only a few cases of the nearly unknown hypoplastic meniscus abnormality have been
      described. A case report of an incidental finding in a young female with a
      bilateral hypoplastic medial menisci is presented and, as far as we know, is the
      first report of bilateral hypoplasia of the medial meniscus in the literature.

PMID- 15968532
TI  - A long-term follow-up study after medial patellofemoral ligament reconstruction
      using the transferred semitendinosus tendon for patellar dislocation.
AB  - The management of patellar dislocation syndrome has traditionally been difficult.
      There are no golden standard methods for patellar dislocations probably due to
      the many etiologies. However, it is known that medial patellofemoral ligament
      (MPFL) is damaged when the patella is dislocated. The purpose of this study is to
      examine whether our method of MPFL reconstruction is useful for the treatment of
      dislocated patellae and unstable patellae. Forty-six knees (43 patients) of 68
      knees (65 patients) that were operated on using our surgical procedure for MPFL
      reconstruction with the advancement of the vastus medialis or the MPFL
      reconstruction with Insall's procedure were followed up for at least 5 years. The
      patient age ranged from 6 to 43 years. These knees consisted of six habitual
      dislocation patellae, twenty-six recurrent dislocation patellae, ten traumatic
      dislocation patellae, and four unstable patellae. The patients were evaluated pre
      operatively and more than three times post-operatively at 6, 12, 36, 60, or 120
      months. No patient experienced patellar dislocation after surgery. Their post
      operative Kujala's scores were significantly improved. On conventional X-ray and
      on stress X-ray evaluations, the mean values for congruence angle, tilting angle,
      lateral shift ratio, medial stress shift ratio, and lateral stress shift ratio at
      the final follow-up (60 or 120 months) were demonstrated to be within the normal
      range. We conclude that our MPFL reconstruction method with the advancement of
      the vastus medialis or with Insall's procedure might be recommended for the
      treatment of habitual, recurrent, and indeed any other type of patellar
      dislocation, as well as for unstable patellae.

PMID- 15968533
TI  - Herbert screw fixation and reverse guided drillings, for treatment of types III
      and IV osteochondritis dissecans.
AB  - We evaluated the outcome in 10 young patients, ages ranging from 15 to 26, with
      types III and IV osteochondritis dissecans of the knee, treated with Herbert
      screws fixation and reverse guided drillings. The disease involved the medial
      femoral condyle in eight patients and the lateral in two. Diagnosis and
      preoperative planning based on plain radiographs (AP, lateral and tunnel view)
      and MRI (in seven patients). Fixation of the fragment with Herbert screws using a
      mini-arthrotomy technique and additional reverse drillings behind the crater of
      the lesion using the ACL aiming devise were performed in all patients. Post
      operatively, no weight bearing was recommended for at least three months. The
      follow-up ranged from 15 months to 38 months (mean 27 months). According to the
      subjective questionnaire of the International Cartilage Repair Society (ICRS)
      scale, seven patients had normal knees, two had nearly normal knees and one
      abnormal. The Lysholm Knee score ranged 65-96 points (mean 88 points). All
      patients except one returned to their previous activities and they were satisfied
      with the result. Radiological union of the fragment was found in 9/10 patients
      (six grade III, three grade IV). Progressive flattening of the injured femoral
      condyle was noticed in two patients (grade III). Securing the lesion using
      Herbert screws in combination with reverse guided drillings seems to be an
      effective treatment choice for detached or displaced osteochondral fragments.

PMID- 15968534
TI  - Repeated lung inflations and deterioration in gas exchange.

PMID- 15968535
TI  - Gene transfer of the pancaspase inhibitor P35 reduces myocardial infarct size and
      improves cardiac function.
AB  - Myocardial infarction and subsequent reperfusion lead to the activation of
      apoptosis, and the final destruction of the cell. The aim of this study was to
      show that broad-scale inhibition of caspases, the main executioners of apoptosis,
      improves functional outcome after ischemia and reperfusion in an in vivo model.
      Twenty male Wistar rats were directly injected with an adenovirus, encoding the
      baculoviral protein p35. Nineteen rats served as controls, and were injected with
      a virus only encoding green fluorescent protein (GFP). After 3 days, 12 animals
      were used for Langendorff perfusion experiments, the other 27 animals were
      submitted to in vivo infarction. Myocardial infarction was induced by ligation of
      the left anterior descending artery (LAD) for 30 min, and reperfusion for 24 h.
      Echocardiographic and hemodynamic measurements were made 24 h after infarction.
      Infarct size was assessed in all animals histologically. In both, in vivo and
      Langendorff perfused hearts, myocardial infarct size was significantly reduced in
      the p35 group (for in vivo experiments: 0.11+/-0.03 vs 0.33+/-0.03 in the GFP
      group, p<0.01), as was the ratio of infarct size to area at risk (6 vs 17%,
      p<0.01). Left ventricular function was similar in both groups prior to
      infarction, but was significantly less compromised after infarction in the p35
      group. The left ventricular systolic pressure after infarction was higher in the
      p35 group (107+/-5 vs 92+/-4 mmHg, p<0.05), as was the maximal rate of rise of
      left ventricular systolic pressure dp/dt (5,659+/-585 vs 4,634+/-256 mmHg s(-1),
      p<0.05). Adenoviral gene transfer of the caspase inhibitor p35 leads to a
      significant reduction of the myocardial infarct size after ischemia and
      reperfusion. Hemodynamic variables were significantly improved by treatment with
      p35. Cardiac restricted inhibition of apoptosis seems to be a promising approach
      for ameliorating the effects of ischemia and reperfusion.

PMID- 15968536
TI  - TLR-2 gene Arg753Gln polymorphism is strongly associated with acute rheumatic
      fever in children.
AB  - The recently described family of toll-like receptors (TLRs) is a key player in
      host immunity by mediating inflammatory reactions against a wide range of
      pathogens. Mutations and polymorphisms in TLRs have revealed the importance of
      TLRs in human defence against diseases. TLR-2 is reported to interact with
      different bacterial structures, including lipoproteins, peptidoglycan and
      lipoteichoic acid. To assess the role of TLR-2 gene polymorphism in acute
      rheumatic fever (ARF) etiopathology, 61 independent Caucasian Turkish patients
      and 91 child and 116 adult controls were studied. Antistreptolycin O, C-reactive
      protein, sedimentation and white blood cell counts were studied to evaluate the
      clinical characteristics of the patients. Genomic DNA was extracted from
      peripheral blood using a standard column extraction technique. The Arg753Gln and
      Arg677Trp polymorphisms were genotyped by polymerase chain reaction (PCR)
      restriction fragment length polymorphism. The PCR products for the TLR-2 gene
      were analysed on 1.5% agarose gel pre-stained with ethidium bromide. Compared
      with healthy adult controls, the Arg753Arg genotype was significantly decreased
      in the entire group of ARF cases [odds ratio (OR) 0.01, 95% confidence interval
      (95% CI) 0.0034-0.031, p<0.0001]. Significantly, ARF patients were just 16 times
      more frequent with Gln allele (OR 15.6, 95% CI 7.87-30.8, p<0.0001). Moreover,
      evidence for an intensifying effect of the Gln allele was noteworthy when
      patients with Arg753Gln genotype were compared with healthy controls (OR 97.1,
      95% CI 32.5-290, p<0.0001). However, no Arg677Trp polymorphism was detected in
      either patients or controls. Our data suggest that there is strong evidence for
      the biological role of TLR-2 in ARF. The common TLR-2 Arg to Gln polymorphism at
      position 753 significantly contributes to the pathogenesis of ARF. These results
      will allow the construction of a profile of individuals prone to ARF and may
      assist in developing new therapies.

PMID- 15968537
TI  - Analysis of DNA methylation related to rice adult plant resistance to bacterial
      blight based on methylation-sensitive AFLP (MSAP) analysis.
AB  - DNA methylation is known to play an important role in the regulation of gene
      expression in eukaryotes. The rice cultivar Wase Aikoku 3 becomes resistant to
      the blight pathogen Xanthomonas oryzae pv. oryzae at the adult stage. Using
      methylation-sensitive amplified polymorphism (MSAP) analysis, we compared the
      patterns of cytosine methylation in seedlings and adult plants of the rice
      cultivar Wase Aikoku 3 that had been inoculated with the pathogen Xanthomonas
      oryzae pv. oryzae, subjected to mock inoculation or left untreated. In all, 2000
      DNA fragments, each representing a recognition site cleaved by either or both of
      two isoschizomers, were amplified using 60 pairs of selective primers. A total of
      380 sites were found to be methylated. Of these, 45 showed differential cytosine
      methylation among the seedlings and adult plants subjected to different
      treatments, and overall levels of methylation were higher in adult plants than in
      seedlings. All polymorphic fragments were sequenced, and six showed homology to
      genes that code for products of known function. Northern analysis of three
      fragments indicated that their expression varied with methylation pattern, with
      hypermethylation being correlated with repression of transcription, as expected.
      The results suggest that significant differences in cytosine methylation exist
      between seedlings and adult plants, and that hypermethylation or hypomethylation
      of specific genes may be involved in the development of adult plant resistance
      (APR) in rice plants.

PMID- 15968538
TI  - Size structure and substitutability in an odonate intraguild predation system.
AB  - Interactions between different size classes of predator species have the
      potential to influence survival of prey species in intraguild predation (IGP)
      systems, but few studies test for these effects. Using a substitutive design in a
      field setting, I measured the effects of two size classes of IG predators (large
      and small larvae of the dragonfly Anax junius) on the mortality of IG prey
      (larvae of the dragonfly Pachydiplax longipennis). I also examined whether
      combinations of large A. junius and P. longipennis and small A. junius and P.
      longipennis had substitutable effects on shared prey (larvae of the damselfly
      Ischnura verticalis). The presence of both size classes of A. junius, when alone
      and in combination with P. longipennis, significantly increased mortality of I.
      verticalis. In the presence of P. longipennis, large and small A. junius had
      similar effects on the mortality of I. verticalis, and effects of size-structured
      assemblages of A. junius were similar to the effects of each size class alone at
      the same density. The effects of the two size classes of A. junius on P.
      longipennis differed, and P. longipennis mortality was lower when exposed to size
      structured assemblages of A. junius than when exposed to only large A. junius at
      the same density. Results were similar to those in a laboratory study, although
      the effect of P. longipennis on I. verticalis was much lower in the field
      setting. These results demonstrate that interactions between different size
      classes of IG predators promote the survival of IG prey and highlight the
      importance of within-species size structure as a characteristic that may promote
      the coexistence of predators in IGP systems.

PMID- 15968539
TI  - Density dependence, spatial scale and patterning in sessile biota.
AB  - Sessile biota can compete with or facilitate each other, and the interaction of
      facilitation and competition at different spatial scales is key to developing
      spatial patchiness and patterning. We examined density and scale dependence in a
      patterned, soft sediment mussel bed. We followed mussel growth and density at two
      spatial scales separated by four orders of magnitude. In summer, competition was
      important at both scales. In winter, there was net facilitation at the small
      scale with no evidence of density dependence at the large scale. The mechanism
      for facilitation is probably density dependent protection from wave dislodgement.
      Intraspecific interactions in soft sediment mussel beds thus vary both temporally
      and spatially. Our data support the idea that pattern formation in ecological
      systems arises from competition at large scales and facilitation at smaller
      scales, so far only shown in vegetation systems. The data, and a simple,
      heuristic model, also suggest that facilitative interactions in sessile biota are
      mediated by physical stress, and that interactions change in strength and sign
      along a spatial or temporal gradient of physical stress.

PMID- 15968541
TI  - [Evidential basis in bariatric surgery].
AB  - Bariatric surgery is currently considered the best treatment option for morbid
      obesity. With the rapid development of laparoscopic techniques, a significant
      increase in the number bariatric procedures in recent years can be observed.
      Various surgical techniques to treat morbid obesity have been described, but only
      few prospective studies compare the different procedures, leading to a lack of
      evidence for their use. However, from the available literature some general
      recommendations can be given: (a) preoperative workup in an interdisciplinary
      team is mandatory, (b) primary bariatric procedures should be performed
      laparoscopically, and (c) the combination of restrictive and malabsorptive
      techniques is more efficient than a purely restrictive method, which is also true
      for the treatment of comorbid diabetes and arterial hypertension. In this paper,
      we present recent developments in bariatric surgery, with special emphasis on the
      available evidence for the best treatment of morbidly obese patients.

PMID- 15968542
TI  - Palliative management strategies of advanced gastrointestinal carcinoid
      neoplasms.
AB  - BACKGROUND/AIMS: Optimal management of gastrointestinal carcinoid neoplasms that
      metastasize to the liver is controversial. Although operative resection seems to
      be the most effective approach to metastatic disease, hepatic metastases are
      usually multicentric and often non-resectable. We investigated the effectiveness
      of several forms of palliative tumor cytoreduction followed by administration of
      somatostatin analogues in advanced carcinoid neoplasms. METHODS: We reviewed our
      experience with 34 patients with gastrointestinal carcinoid neoplasms. Eighteen
      patients had metastases and 14 had hormonal symptoms. Twenty-two patients
      underwent radical surgery, ten with multiple liver metastases were treated with a
      combination of debulking (resection, radiofrequency ablation, chemoembolization),
      followed by medical treatment with long-acting octreotide and eventually by
      radiolabelled somatostatin analogues, and two patients with intractable disease
      received only biotherapies. RESULTS: The six patients with metastatic disease who
      underwent radical curative liver resection had a median survival of 52 months,
      compared with a median survival of 48 months in the ten patients who underwent
      palliative debulking. Symptomatic improvement was observed in all the patients
      after debulking procedures. The two patients who underwent only medical treatment
      died after 9 and 18 months. CONCLUSIONS: Aggressive tumor debulking should be
      performed in patients with liver metastases already at diagnosis even when
      complete resection is not feasible because the combination of cytoreductive
      procedures followed by biotherapies may provide good long-term survival and
      achieves symptom control in most patients with advanced disease.

PMID- 15968543
TI  - Gonadoblastoma: evidence for a stepwise progression to dysgerminoma in a
      dysgenetic ovary.
AB  - Gonadoblastomas are neoplasms of dysgenetic gonads which may undergo regression
      or become overgrown by malignant germ cell tumors (mGCTs). Since little is known
      about their relationship to normal gonadal development and mGCTs, we studied the
      phenotype and antigenic profile of gonadoblastomas in comparison with adjacent
      dysgerminomas and fetal gonads. Three cases of gonadoblastomas and fetal gonads
      of both sexes were analyzed using oncofetal markers to M2A-antigen (M2A), germ
      cell alkaline phosphatase (PLAP/GCAP), receptor tyrosine kinase c-kit (c-kit),
      and somatic angiotensin converting enzyme (sACE) as well as the proliferation
      marker MIB-1. Morphologically, microfollicular pattern of gonadoblastomas showed
      a fetal germ cell organization reminiscent of oocytic clusters of fetal ovaries.
      They contained both cell types, similar to oocytes (M2A-, GCAP-, c-kit+/-, sACE-)
      and oogonia (M2A+, GCAP+, c-kit+, sACE+). The percentage of germ cells
      immunoreactive for oncofetal markers and the proliferation index increased from
      microfollicular over coronary patterns to adjacent dysgerminomas. Supportive
      cells of gonadoblastomas showed a uniform phenotype (CK18+, vimentin+, sACE+,
      alpha-inhibin+, M2A-) but in contrast to fetal germ cells lacked a clear
      equivalence to fetal tissues. Our results show that gonadoblastomas mimic female
      fetal ovary and exhibit a stepwise progression from follicular pattern to
      coronary pattern and finally to dysgerminomas.

PMID- 15968544
TI  - Secondary glioblastoma with advanced neuronal immunophenotype.
AB  - We describe an unusual progression of astrocytoma into secondary glioblastoma
      exhibiting advanced neuronal immunophenotype. A tumor of the left frontal lobe of
      a 35-year-old man was diagnosed as astrocytoma. The tumor was treated by partial
      removal with postoperative chemoradiotherapy, followed by extensive removal of
      the residual regrowing tumor 5 month later. A secondary tumor was discovered and
      partially resected 8 years later, but the patient died 11 months following the
      operation due to extensive tumor progression showing subarachnoidal and
      intraventricular dissemination. The secondary tumor was small cell-predominant,
      highly proliferative tumor with an extremely high MIB-1 labeling index (80%).
      Unexpectedly, most of the tumor cells were positive for neuronal markers
      (synaptophysin and NeuN), but not for glial fibrillary acidic protein (GFAP).
      Retrospective examination of the original tumor revealed not only diffuse GFAP
      expression, but also neuronal marker expressions in small numbers of tumor cells
      that were hard to discriminate from the other cells on hematoxylin-eosin (HE)
      stain. This way of malignant progression of astrocytoma was quite unusual.
      Although the secondary tumor was classified as glioblastoma according to World
      Health Organization (WHO) classification (2000), it might be categorized into new
      variants of malignant glioneuronal tumors proposed recently.

PMID- 15968546
TI  - Inter-laboratory validation of PCR-based detection of Mycobacterium tuberculosis
      in formalin-fixed, paraffin-embedded tissues.
AB  - The present study is based on the initiative for quality assurance in pathology
      of the German Society of Pathology and the Professional Association of German
      Pathologists. Four panel laboratories with experience and expertise in polymerase
      chain reaction (PCR) detection of Mycobacterium tuberculosis were selected to
      establish the prerequisites for continuous external laboratory trials, in
      particular, by providing pre-tested specimens and evaluation criteria for
      participating institutes. In the first step, the four panel laboratories
      performed an internal trial to test their own reliability and reproducibility.
      Paraffin sections and DNA preparations from 34 tissues (25 clinical specimens and
      9 controls) totalling to 66 samples were evaluated by each panel institute
      according to their own protocols. The methodologies differed and are described in
      detail. Despite these differences, a high degree of inter-laboratory reliability
      was achieved. In this report, we summarise our results including the correlation
      with the histology and provide recommendations for applying PCR-based methodology
      for the detection of mycobacterial DNA in surgical specimens. Supplementary data
      are available online at http://www.charite.de/ch/patho (rubric "Forschung"). Pre
      tested specimens are now available for the external trial and can be ordered from
      the steering institute via Oligene (http://www.oligene.com/). All molecular
      pathology laboratories are invited to participate in this quality assurance
      initiative.

PMID- 15968547
TI  - Augmented expression of metallothionein and glutathione S-transferase pi as
      unfavourable prognostic factors in cisplatin-treated ovarian cancer patients.
AB  - Resistance to cis- or carboplatin represents the principal cause of therapeutic
      failures in ovarian carcinoma. The phenomenon of resistance to platinum-based
      drugs is partly related to expression of metallothionein (MT) and of glutathione
      S-transferase pi (GST-pi), but opinion on the subject is discordant.
      Documentation of a negative predictive effect of MT and GST-pi expression for the
      therapy employing platinum-based drugs would permit to select resistant cases in
      which other therapeutic approaches could be employed. The present study aimed at
      examining the relation between intensities of MT and GST-pi expressions in
      ovarian carcinomas and dynamics of the clinical course in the neoplastic disease
      in a group of cisplatin-treated patients. The analyses were performed on samples
      of ovarian carcinoma originating from 43 first-look laparotomies (FLLs) and, in
      30 cases, from second-look laparotomies (SLL) from the same patients.
      Immunohistochemical reactions were performed on paraffin sections of studied
      tumors, using monoclonal antibodies to MT and GST-pi. The calculations showed
      that in cases with augmented expression of MT, mortality was higher. On the other
      hand, augmented expression of GST-pi predisposed to more frequent relapses,
      deaths and progression of the tumor. Kaplan-Meier analysis showed that a
      significantly shorter survival time was linked to cases of higher expression of
      MT at FLL and of higher expression of GST-pi at FLL, whereas a shorter
      progression-free time was manifested by cases with higher expression of GST-pi at
      FLL. The performed investigations indicate that augmented expressions of MT at
      FLL and GST-pi at FLL in ovarian cancer represent an unfavourable predictive
      factor in cisplatin-treated patients.

PMID- 15968545
TI  - Microinvasive germ cell tumor of the testis.
AB  - Microinvasive germ cell tumor (MGCT) consists of a limited number of malignant
      germ cells in the intertubular tissue of the testis. The cells have large nuclei,
      prominent nucleoli, abundant clear cytoplasm, and distinct cellular borders in
      hematoxylin and eosin staining. MGCT can be the first stage of malignancy in the
      development of testicular germ cell tumor (TGCT). Biopsies from men with
      maldescended testes have been reported to contain intratubular germ cell
      neoplasia, unclassified (IGCN) and MGCT in 1.8% of the examined cases (95% CI 0.5
      4.6%). MGCT has also been found in testes of subfertile men and in the
      contralateral testis of patients with TGCT. MGCT is a frequent finding (19%) in
      the testicular tissue adjacent to an overt TGCT. Men with a high risk of TGCT may
      gain from screening for precursor lesions of TGCT with ultrasonography of the
      testes followed by a testicular biopsy if suspicious abnormalities are found:
      Treatment is high-voltage radiotherapy for intratubular germ cell neoplasia
      (IGCN), and orchidectomy for MGCT and germ cell tumor in situ, either
      intratubular seminoma or intratubular embryonal carcinoma. After local treatment,
      patients with precursor lesions can be followed with a surveillance program. The
      mRNA levels of invasion-related genes were evaluated based on a DNA microarray
      data set, and we found two gene abnormalities most relevant for the invasion of
      malignant germ cells: matrix metalloproteinase 9 (MMP9) and plasminogen
      activator, urokinase (PLAU) genes were up-regulated in a study comparing tissue
      samples of TGCT and IGCN.

PMID- 15968548
TI  - Inflammatory pseudotumor of the liver associated with malignant disease: report
      of two cases and a review of the literature.
AB  - Two cases of inflammatory pseudotumor (IPT) of the liver associated with
      gastrointestinal tract cancer are reported. In addition, the etiological
      correlation between IPT and abscesses of the liver in cancer patients is
      discussed. The first patient was a 63-year-old woman who underwent distal
      gastrectomy and partial hepatectomy under a diagnosis of stomach cancer with
      liver metastasis. The second patient was a 66-year-old man who had undergone
      surgery for rectal cancer 6 years previously and underwent partial hepatectomy
      under a diagnosis of metastasis of rectal cancer to the liver. The gastric cancer
      was a papillary adenocarcinoma limited to the mucosa, and the rectal cancer was a
      moderately differentiated adenocarcinoma limited to the subserosa. The resected
      liver tumor in the first case measured 5.5 x 5.0 x 4.0 cm and was 2.5 x 1.9 x 1.6
      cm in the second. The cut surface showed that both masses were well circumscribed
      and divided into lobules by fibrous tissue. They were yellowish white in color
      and there was no evidence of necrosis or hemorrhage. Histologically the masses
      consisted of fibrous areas and cellular areas, and the cellular areas consisted
      of fascicles of plump spindle cells mingled with varying numbers of plasma cells,
      lymphocytes, and histiocytes. The masses were diagnosed as IPTs. Obliterating
      phlebitis suggesting infection via the portal vein was seen in the adjacent liver
      tissue in both cases. According to previous cases reported in the literature,
      there are three types of cancers associated with hepatic IPT: gastrointestinal
      tract cancer, biliary tract cancer, and cancers that need strong systemic
      chemotherapy. The underlying cancer types of IPT of the liver are almost similar
      to those associated with pyogenic liver abscesses suggesting the etiological
      correlation between IPT and abscesses of the liver.

PMID- 15968549
TI  - Rb1cc1 is critical for myoblast differentiation through Rb1 regulation.
AB  - Rb1-inducible coiled-coil 1 (Rb1cc1) expressed at high levels is associated with
      the maturation of human embryonic musculoskeletal cells. To clarify the molecular
      role of Rb1cc1 in muscular differentiation, we investigated the expression of
      Rb1cc1 and other genes that regulate differentiation in murine embryonic tissues
      and in C2C12 myoblasts. We also evaluated the effects of RNA interference (RNAi)
      mediated Rb1cc1 knockdown on C2C12 myoblast differentiation. After Rb1cc1, Rb1
      and myosin heavy chain (Myhc) were expressed in mouse embryonic muscles. The
      synchronous expression of Rb1cc1 and Rb1 predicted Myhc expression during C2C12
      myoblast differentiation. RNAi-mediated knockdown of Rb1cc1 led to Rb1
      suppression, and C2C12 myoblasts failed to differentiate. These results indicated
      that Rb1cc1 is a potent regulator of the Rb1 pathway and a novel mediator that
      plays a crucial role in muscular differentiation. Rb1cc1 expression is, thus, a
      prerequisite for myogenic differentiation.

PMID- 15968550
TI  - Tooth development in vitro in two teleost fish, the cichlid Hemichromis
      bimaculatus and the cyprinid Danio rerio.
AB  - A technique for organotypic in vitro culture with serum-free medium was tested
      for its appropriateness to mimic normal odontogenesis in the cichlid fish
      Hemichromis bimaculatus and the zebrafish Danio rerio. Serial semithin sections
      were observed by light microscopy to collect data on tooth patterning and
      transmission electron microscopy was used to compare cellular and extracellular
      features of tooth germs developing in vitro with the situation in vivo. Head
      explants of H. bimaculatus from 120 h post-fertilization (hPF) to 8.5 days post
      fertilization (dPF) and of zebrafish from 45 hPF to 79 hPF and adults kept in
      culture for 3, 4 or 7 days revealed that tooth germs developed in vitro from
      explants in which the buccal or pharyngeal epithelium was apparently
      undifferentiated and, when present at the time of explantation, they continued
      their development up to a stage of attachment. In addition, the medium allowed
      the morphogenesis and cytodifferentiation of the tooth germs similar to that
      observed in vivo and the establishment of a dental pattern (place and order of
      tooth appearance and of attachment) that mimicked that in vivo. Organotypic
      culture in serum-free conditions thus provides us with the means of studying
      epithelial-mesenchymal interactions during tooth development in teleost fish and
      of analysing the genetic control of either mandibular or pharyngeal tooth
      development and replacement in these polyphyodont species. Importantly, it allows
      heads from embryonically lethal (zebrafish) mutants or from early lethal
      knockdown experiments to develop beyond the point at which the embryos normally
      die. Such organotypic culture in serum-free conditions could therefore become a
      powerful tool in developmental studies and open new perspectives for craniofacial
      research.

PMID- 15968551
TI  - [Is a blockade of the lateral cutaneous nerve of the thigh an alternative to the
      classical femoral nerve blockade for knee joint arthroscopy? A randomised
      controlled study].
AB  - BACKGROUND: Gaps in the distribution area of the lateral femoral cutaneous nerve
      (LFCN) are assumed to be the reason for pain caused by a thigh tourniquet when
      performing a femoral nerve (FN) block according to Winnie. The aim of the study
      was to evaluate if a direct single blockade of the LFCN in patients undergoing
      knee surgery resulted in a better tolerance to the tourniquet with equally good
      analgesic quality during surgery. METHODS: A total of 40 patients undergoing knee
      arthroscopy received a proximal blockade of the sciatic nerve and randomly either
      an FN or an LFCN block. Practicability, onset time, quality of sensory and motor
      block, and clinical effectiveness during tourniquet and surgery were assessed.
      RESULTS: Stimulation time was significantly longer in the LFCN than in the FN
      group. Quality of sensory and motor block was worse in the LFCN than the NF
      group. Of the LFCN patients 65% indicated troublesome paraesthesia or pain when a
      tourniquet was placed, compared to 35% of the FN patients. Of the LFCN patients
      50% had pain during cutaneous incision, compared to none of the FN group. During
      the course of surgery, 70% of the LFCN patients needed supplemental systemic
      analgesia, but this was required by only 30% of the FN group. CONCLUSION: An LFCN
      block is not a suitable alternative to an FN block for regional anaesthesia. For
      patients with contraindications for an FN block according to Winnie (e.g. vessel
      surgery in the groin) other more effective methods are available.

PMID- 15968552
TI  - [Airways and respiratory function in obese patients. Anaesthetic and intensive
      care aspects and recommendations].
AB  - In obese patients, perioperative pulmonary complications have an increased
      frequency and are associated with higher morbidity and mortality compared with
      non-obese patients. The management of surgical procedures in these patients is a
      challenge for the anaesthetist. Knowledge of pathophysiological and
      pharmacological aspects of the obese patients' condition is essential for their
      care during preoperative assessment, intra-operative management and, if
      necessary, postoperative intensive care. Special information on airway and lung
      protection as well as cases involving laparoscopic surgery, obstetric and
      paediatric anaesthesia in obese patients are also discussed.

PMID- 15968553
TI  - Mental fatigue disturbs local processing more than global processing.
AB  - Focusing of attention is influenced by external features such as the presence of
      global or local target stimuli, but also by motivation and mood states. In the
      current study, we examined whether working on cognitively demanding tasks for 2
      h, which induces mental fatigue, subsequently had a differential effect on global
      and local processing. The results showed that, compared to non-fatigued
      participants, fatigued participants particularly displayed compromised local
      processing. This indicates that mental fatigue may also manifest itself as
      effects on attentional focusing. The findings of this study are in line with
      recent ideas about the nature of fatigue-related cognitive deficits, implying
      disturbances in the control over attention and behaviour.

PMID- 15968554
TI  - Three-tesla imaging of the knee: initial experience.
AB  - PURPOSE: To assess 3-T imaging of the knee. MATERIALS AND METHODS: We reviewed
      357 3-T magnetic resonance images of the knee obtained using a dedicated knee
      coil. From 58 patients who had arthroscopy we determined the sensitivity and
      specificity for anterior cruciate ligament (ACL) tear and medial and lateral
      meniscal tear. RESULTS: A chemical shift artifact showed prominently at 3 T even
      after improvements had been made by increasing the bandwidth. For complete ACL
      tear the sensitivity was 100% (95% confidence interval, CI, 75.30-100.00), and
      the specificity was 97.9% (95% CI 87.7-99.9). For the medial meniscus the
      sensitivity was 100.00% (95% CI 90.0-100.00), and the specificity was 83.3%(95%
      CI 66.6-95.3). For the lateral meniscus the sensitivity was 66.7% (95% CI 38.4
      88.2), and the specificity was 97.6% (95% CI 87.1-99.9). CONCLUSIONS: In general
      3-T imaging allows a favorable display of anatomy and pathology. The lateral
      meniscus was assessed to be weaker than the other anatomic structures. Three
      tesla imaging allows increased signal-to-noise ratio, increased resolution, and
      faster scanning times.

PMID- 15968556
TI  - Post-traumatic cystic lesion following fracture of the radius.
AB  - Post-traumatic cystic lesions are an uncommon complication of fractures in
      children. They are benign, asymptomatic, non-expansive and tend to resolve
      spontaneously. Their cause seems to be the invasion of bone-marrow fat by
      subperiosteal hematoma, which may be visible on radiographs during fracture
      consolidation of the newly formed subperiosteal bone. The case we present is of
      cyst formation following a fracture of the distal radius and we evaluate the role
      of yellow bone marrow in the pathogenesis of the cyst. Its typical features clear
      differentiation from other lesions, preventing unnecessary and, possibly,
      invasive examinations.

PMID- 15968555
TI  - MR imaging evaluation of the postoperative knee: ligaments, menisci, and
      articular cartilage.
AB  - The surgical management of knee injuries has increased in recent years.
      Postoperative magnetic resonance (MR) imaging of the knee following surgical
      intervention serves an important role in the diagnostic evaluation of patients
      with recurrent or residual symptoms following surgical intervention. MR imaging
      additionally assists in the noninvasive documentation of temporal changes at the
      surgical site potentially reflective of procedural success, or failure.
      Background understanding of the common surgical procedures performed, their
      normal postoperative MR imaging appearance, and imaging features of potential
      procedural complications are essential in the accurate evaluation of patients
      following prior knee surgery. The focus of the following article is to review the
      clinical and MR imaging features of the postoperative knee following prior
      surgical treatment of ligamentous, meniscal, and articular cartilage injuries of
      the joint.

PMID- 15968557
TI  - Deposition of intraosseous fat in a degenerating simple bone cyst.
AB  - A simple bone cyst in the proximal humerus of an 18-year-old man was treated by
      percutaneous ablation with alcohol irrigation. Subsequent involution of the cyst
      was associated with fatty replacement within the intraosseous defect. A possible
      relationship between involuting bone cyst and apparent intraosseous lipoma is
      discussed.

PMID- 15968558
TI  - Evidence-based management of steroid-sensitive nephrotic syndrome.
AB  - Using data from systematic reviews and randomised controlled trials, the evidence
      for managing steroid sensitive nephrotic syndrome (SSNS) is reviewed. In the
      initial episode, increased duration (3-7 months) of prednisone compared with 2
      months significantly reduced the risk for relapse at 12-24 months [relative risk
      (RR) 0.70; 95% confidence intervals (CI) 0.58-0.84] without increase in adverse
      effects. Six months of prednisone was significantly more effective than 3 months
      (RR 0.57; 95% CI 0.45-0.71). Higher prednisone doses given for the same duration
      reduced the risk of relapse (RR 0.59; 95% CI 0.42-0.84) suggesting that both dose
      and duration of prednisone therapy lead to prolonged remission. In relapsing SSNS
      prolonged prednisone treatment, daily prednisone during infections, oral or
      intravenous cyclophosphamide, chlorambucil, levamisole and cyclosporin
      significantly reduced the risk of relapse. Comparative effects of these options
      remain uncertain because of the absence of head-to-head trials, but existing
      trial evidence is strongest for cyclophosphamide and cyclosporin. Further
      adequately powered multinational trials are required to determine the optimum
      induction dose and duration of prednisone in the initial episode of SSNS and to
      determine the relative efficacies of immunosuppressive agents and the efficacy of
      newer agents, including mycophenolate and tacrolimus, in relapsing SSNS.

PMID- 15968559
TI  - Clinical features and outcome of childhood minimal change nephrotic syndrome: is
      genetics involved?
AB  - The pathogenesis of minimal change nephrotic syndrome (MCNS) is still unknown. We
      performed a clinical and genetic evaluation of 104 adults (mean age 35 years) who
      presented with MCNS in childhood (mean follow-up 30 years). Clinical data and the
      present health status were evaluated. Also, the genes encoding the four major
      slit diaphragm proteins, nephrin, podocin, Neph1 and CD2-associated protein were
      sequenced in 38 patients with MCNS of varying severity. MCNS presented at the
      mean age of 5 years, and 80% of the patients relapsed 1-28 (median 3) times
      during childhood. The 14 subjects (14%) who had proteinuric episodes still in
      adulthood had a refractory disease already as children. The participants did not
      show a strong tendency for allergy or immune diseases, and no familial clustering
      of MCNS was observed. The genetic analyses revealed heterozygous amino acid
      changes in nephrin and podocin in 10 of the 38 patients studied. On the other
      hand, the genes coding for Neph1 and CD2AP were highly conserved and no amino
      acid substitutions were detected. In conclusion, MCNS is a multifactorial
      disease, in which genetics play a minor role. Allelic variants of the podocyte
      proteins may, however, modify the phenotype in occasional individuals.

PMID- 15968560
TI  - [The role of ultraviolet irradiation in malignant melanoma].
AB  - The incidence of melanoma has been rising during the past 40 years and may be the
      result of lifestyle changes that have led to an increased sun exposure in fair
      skinned people. Ultraviolet radiation (UVR) is believed to be the main causative
      factor in melanoma development with an acute intermittent exposure being more
      relevant than a chronic cumulative one. While UVB (280-320 nm) can directly cause
      DNA damage (UVB fingerprint mutations) in the cells of the epidermis, UVA (320
      400 nm) induces damage indirectly by the formation of reactive oxygen species.
      Since UV-associated mutations are rare in melanoma, it is speculated that UVR
      supports melanoma development by indirect effects, e.g. immunosuppression or
      stimulation of growth factors in the skin. Taken together, animal models and
      epidemiological data suggest a UVA-associated pathogenesis of melanoma that puts
      into question the effectiveness of sunscreens in melanoma prevention.

PMID- 15968561
TI  - Reimbursement and clinical guidance for pharmaceuticals in Sweden: do health
      economic evaluations support decision making?
AB  - Introduction of the new Pharmaceutical Benefits Board (LFN; 1 October 2002) has
      markedly changed the principles of pricing and reimbursement of drugs in Sweden.
      The Board is required to make decisions based on information on cost
      effectiveness, and pharmaceutical companies must submit economic evaluations when
      relevant as part of their applications for reimbursement. This study examined
      experience to date regarding the use of health-economic evaluations and cost
      effectiveness information by the LFN. We also describe activities and the use of
      cost-effectiveness analysis by Swedish local formulary committees organized by
      the 21 county councils. It is concluded that economic evaluations have supported
      decision making by LFN, although cost-effectiveness seems to be of varying
      importance in different situations. While the use of health-economic evaluations
      and the outcome of decision making by LFN are similar to comparable committees in
      other countries, there is presently a gap in this sense between the LFN and
      Swedish local formulary committees. Coordinated decision making is much needed
      but may be difficult to implement as the perspective, expertise, and objectives
      of the two public authorities differ.

PMID- 15968562
TI  - Comparison of general practitioner records and patient self-report questionnaires
      for estimation of costs.
AB  - This study compared resource use data and estimated costs over a 12-month period,
      based on patient self-report questionnaires and general practitioner records. The
      level of agreement was measured by weighted kappa. Differences in total costs
      were plotted against mean total costs. Of 324 patients with complete GP records
      for the period only 85 (26.2%) had complete self-report data. The recorded number
      of contacts per patient was higher for patient questionnaires than GP records
      (17.20 vs. 12.64), and the level of agreement between the two sources was
      moderate (kappa(w)=0.465). The plots of differences in total costs showed a
      slight downward bias, suggesting that estimation of total cost from GP records is
      lower than patient questionnaires. The incompleteness of patient questionnaires
      forces reliance on GP records as the main source of information for economic
      evaluations.

PMID- 15968563
TI  - Measuring health-related utility: why the disparity between EQ-5D and SF-6D?
AB  - There remains considerable disagreement concerning the preferred generic utility
      based measure of health-related quality of life for use in constructing quality
      adjusted life years. The recent appearance (in a published form) of a new
      measure, the SF-6D, has highlighted this issue. The SF-6D and EQ-5D have many
      similarities, but marked variation has been shown in the results generated by the
      two instruments. The study reported here is an exploration of why such divergent
      results exist. There are two possible explanations: variation in the descriptive
      component of the instruments and variation in the values applied to health
      states. The results suggest two important conclusions. First, the SF-6D can
      describe severe health states, including states that (according to the EQ-5D
      scoring algorithm) are viewed as worse than the state of being 'dead'. Second,
      much of the large discrepancy between the results generated using the two
      instruments appears to stem from very different valuations being placed on
      similar health states.

PMID- 15968564
TI  - [Skin and soft tissue infections. Surgical procedures for necrotizing soft tissue
      infections].

PMID- 15968565
TI  - [Reconstruction of the tibial diaphysis with transfer of the tibial head onto the
      proximal fibula. Follow-up after 63 years].
AB  - Osteoarthritis of the knee is often diagnosed in the orthopedic trauma practice.
      One major cause is axial deformity with overload. In the case presented here
      osteomyelitis of the tibial diaphysis developed in childhood. Surgical treatment
      consisted of resection of the middle tibial third and transferring the tibial
      head onto the proximal fibula. In this way it was possible to eradicate the
      osteomyelitis of the lower leg and to achieve osseous consolidation between the
      tibia and fibula. Despite the significant shortening of the lower limb and the
      varus axial deformity, the knee joint function was satisfactory in the subsequent
      development. After a long interval without symptoms the patient developed a
      medially accentuated osteoarthritis of the knee.

PMID- 15968566
TI  - [Thoracic inlet syndrome after ESIN of comminuted clavicular fracture].
AB  - Thoracic inlet syndrome is a rare venous obstruction of the upper extremity
      caused by narrowness of the costoclavicular angle. This case report describes an
      obstruction of the vena subclavia after percutaneous elastic stable medullary
      nailing of a comminuted fracture of the clavicle.

PMID- 15968567
TI  - [Pigmented villonodular synovitis of the knee joint].
AB  - Pigmented villonodular synovitis is a rare proliferative disorder of the synovial
      membrane most frequently found in the knee. The etiopathology of the disease is
      still not understood. Present terminology differentiates between a localized
      (LPVNS) and a diffuse (DPVNS) form. Currently, MRI is the diagnostic imaging
      technique of choice. The localized form (LPVNS) can be cured definitely in almost
      all cases by partial arthroscopic synovectomy, whereas the treatment of the
      diffuse form (DPVNS) is discussed controversially concerning an arthroscopic or
      total synovectomy by open arthrotomy. We report a case rarely found in the
      literature of a patient suffering from a diffuse form of PVNS localized in the
      right knee joint. In this case PVNS acted as a locally aggressive and destructive
      lesion of immense extent invading femoral, tibial and fibular bone and the whole
      extending muscular system. We performed a radical synovectomy by open arthrotomy.
      By implanting a tumor prosthesis we prevented progression of the disease. Apart
      from adequate diagnosis, we recommend complete and aggressive resection of the
      affected tissue by performing an open arthrotomy.

PMID- 15968568
TI  - Bilateral otosyphilis in a patient with HIV infection.
AB  - Otosyphilis is a rare but important cause of sensorineural hearing loss and
      dizziness, because this hearing loss can be reversed by early diagnosis and
      aggressive treatment. Moreover, HIV may alter the course of otosyphilis and
      hasten the development of otosyphilis by reducing host cellular immunity. We
      report the case of a 35-year-old HIV-infected patient with bilateral fluctuating
      sensorineural hearing loss and bilateral total vestibular loss caused by
      otosyphilis. We include a discussion of the relationship between otosyphilis and
      HIV infection.

PMID- 15968569
TI  - Pleomorphic adenoma of the external auditory canal.
AB  - Pleomorphic adenoma of the external auditory canal is a rare disease. It is
      considered to derive from the ceruminous glands. The objective of this study is
      to familiarize the clinician with the clinical presentation and treatment of this
      disease. We report the case of a 58-year-old woman. Complete resection should be
      applied for cases in which magnetic resonanace imaging (MRI) and computerize
      tomography (CT) examination indicate no erosion in the bone and cartilage tissue.
      The patient should be seen regularly for recurrence.

PMID- 15968570
TI  - Purification and characterization of a biodegradable plastic-degrading enzyme
      from Aspergillus oryzae.
AB  - We used biodegradable plastics as fermentation substrates for the filamentous
      fungus Aspergillus oryzae. This fungus could grow under culture conditions that
      contained emulsified poly-(butylene succinate) (PBS) and emulsified poly
      (butylene succinate-co-adipate) (PBSA) as the sole carbon source, and could
      digest PBS and PBSA, as indicated by clearing of the culture supernatant. We
      purified the PBS-degrading enzyme from the culture supernatant, and its molecular
      mass was determined as 21.6 kDa. The enzyme was identified as cutinase based on
      internal amino acid sequences. Specific activities against PBS, PBSA and poly
      (lactic acid) (PLA) were determined as 0.42 U/mg, 11 U/mg and 0.067 U/mg,
      respectively. To obtain a better understanding of how the enzyme recognizes and
      hydrolyzes PBS/PBSA, we investigated the environment of the catalytic pocket,
      which is divided into carboxylic acid and alcohol recognition sites. The
      affinities for different substrates depended on the carbon chain length of the
      carboxylic acid in the substrate. Competitive inhibition modes were exhibited by
      carboxylic acids and alcohols that consisted of C4-C6 and C3-C8 chain lengths,
      respectively. Determination of the affinities for different chemicals indicated
      that the most preferred substrate for the enzyme would consist of butyric acid
      and n-hexanol.

PMID- 15968571
TI  - Homozygous diploid deletion strains of Saccharomyces cerevisiae that determine
      lag phase and dehydration tolerance.
AB  - This study identifies genes that determine length of lag phase, using the model
      eukaryotic organism, Saccharomyces cerevisiae. We report growth of a yeast
      deletion series following variations in the lag phase induced by variable storage
      times after drying-down yeast on filters. Using a homozygous diploid deletion
      pool, lag times ranging from 0 h to 90 h were associated with increased drop-out
      of mitochondrial genes and increased survival of nuclear genes. Simple linear
      regression (R2 analysis) shows that there are over 500 genes for which > 70% of
      the variation can be explained by lag alone. In the genes with a positive
      correlation, such that the gene abundance increases with lag and hence the
      deletion strain is suitable for survival during prolonged storage, there is a
      strong predominance of nucleonic genes. In the genes with a negative correlation,
      such that the gene abundance decreases with lag and hence the strain may be
      critical for getting yeast out of the lag phase, there is a strong predominance
      of glycoproteins and transmembrane proteins. This study identifies yeast deletion
      strains with survival advantage on prolonged storage and amplifies our
      understanding of the genes critical for getting out of the lag phase.

PMID- 15968574
TI  - Obesity, health issues, and cardiovascular disease.

PMID- 15968572
TI  - Injection of glutamate into the pedunculopontine tegmental nuclei of anesthetized
      rat causes respiratory dysrhythmia and alters EEG and EMG power.
AB  - The pedunculopontine tegmental nucleus (PPT) has been shown to have important
      functions relevant to the regulation of behavioral states and various motor
      control systems, including breathing control. Our previous work has shown that
      the activation of neurons within the PPT, a structure that is typically active
      during rapid eye movement (REM) sleep, can produce respiratory disturbances in
      freely moving and anesthetized rats. The aim of this study was to test the
      hypothesis that respiratory modulation by the PPT in anesthetized rats can be
      evoked in the absence of other signs of an REM-sleep-like state. We characterized
      electroencephalogram (EEG) and electromyogram (EMG) changes during respiratory
      disturbances induced by glutamatergic stimulation of the PPT in spontaneously
      breathing, adult male Sprague-Dawley rats anesthetized with a ketamine/xylazine
      combination or with nembutal. Respiratory movements were monitored by a
      piezoelectric strain gauge. Two-barrel glass pipettes were used to pressure
      inject glutamate, to probe for respiratory effective sites within the PPT, and to
      inject oil red dye at the end of the experiments for histological verification of
      the injection sites. The EEGs were recorded from the sensorimotor cortex,
      hippocampus, and from the pons contralateral from the injection site. The EMGs
      were recorded from the genioglossus muscle. The initial response to glutamate
      injection into the respiratory modulating region of the PPT was always a
      respiratory pattern disturbance. Subsequent activation of EMG and EEG often
      occurred in ketamine/xylazine-anesthetized rats, but REM-sleep-like patterns were
      not observed. Respiratory pattern and EMG power changes in nembutal-anesthetized
      rats were similar, but EEG activation was never observed. Thus, we conclude that
      respiratory suppression produced by the local activation of PPT neurons may not
      necessarily be accompanied by an REM-sleep-like cortical state in this
      anesthetized model.

PMID- 15968575
TI  - Epidemiology of obesity.
AB  - The prevalence of obesity is increasing at an alarming rate in many parts of the
      world. In White populations living in the west and north of Europe, Australia,
      and the United States, the prevalence of obesity is similarly high in men and
      women. In countries with relatively low gross national product, such as those in
      Central and Eastern Europe, Asia, Latin-America, and Africa, the prevalence is
      1.5 to 2 times higher among women than among men. Within affluent societies, the
      rates of obesity seem to be more common among women at older ages (65 years) and
      in groups with relatively low socioeconomic status. It can be tentatively
      concluded that obesity is particularly common in women living in relatively poor
      conditions.

PMID- 15968576
TI  - Human leptin: an adipocyte hormone with weight-regulatory and endocrine
      functions.
AB  - Leptin is synthesized and secreted primarily by adipocytes, and is present in
      serum in direct proportion to the amount of adipose tissue. The primary role of
      leptin is to provide to the central nervous system a signal of energy intake and
      energy stores in the body so that the hypothalamus can efficiently maintain a
      stable body weight. The receptor for leptin in the hypothalamus signals by
      activation of an associated janus kinase which phosphorylates signal transducer
      and activator of transcription (STAT) proteins that regulate neuronal gene
      expression. Genetic mutations in leptin and its receptor can result in obesity in
      both rodents and humans, supporting a central role for leptin in the regulation
      of body weight. Leptin has also been implicated in a variety of physiological
      processes other than body weight homeostasis. Many of these functions are
      mediated through the central nervous system; however, the presence of leptin
      receptors in tissues throughout the body suggests that leptin can also have
      direct effects on cells and tissues. Serum leptin levels have been associated
      with cardiovascular risk factors after correction for adiposity. Leptin can
      promote platelet aggregation, which requires expression of functional leptin
      receptors on the platelet. Leptin-induced increases in sympathetic nerve activity
      have been suggested to contribute to hypertension, and leptin has been observed
      to increase oxidative stress in cultured endothelial cells. Many of these
      pathophysiologic effects of leptin on the vasculature are most likely of
      importance when leptin levels are elevated in obese subjects due to resistance to
      the weight-reducing effects of the hormone. An improved understanding of the
      effects of leptin on the vasculature will provide valuable insight into the
      relationship between obesity and cardiovascular disease.

PMID- 15968577
TI  - Obesity and cardiovascular disease: pathogenic mechanisms and potential benefits
      of weight reduction.
AB  - The prevalence of obesity in industrialized countries has reached epidemic
      proportions, with about one in three people being obese and another one in three
      people being overweight and at risk of developing obesity. In recent years,
      obesity has gained the traditional tetrad of cardiovascular risk factors of
      smoking: hypertension, dyslipidemia, and dysglycemia. Attention has also focused
      on the importance of abdominal (or central) obesity as a determinant of
      cardiovascular risk, independent of the body mass index. In addition to effects
      on coronary artery disease, obesity has an effect on cardiovascular disease,
      including stroke, ventricular function, peripheral arterial disease, and venous
      thromboembolism. The objectives of this review are to summarize the effects of
      obesity on cardiovascular disease, and the possible mechanisms for these
      associations, and to investigate the effects of weight-loss interventions on the
      burden of cardiovascular disease. Large ongoing clinical outcome trials, such as
      the SOS study, the Look-AHEAD trial, or the SCOUT study, should provide important
      information on the effects of surgical and nonsurgical obesity treatment on
      cardiovascular morbidity and mortality.

PMID- 15968578
TI  - Adipocytokines and metabolic syndrome.
AB  - Recently, adipocytes have been shown to be endocrine cells that secrete a variety
      of bioactive substances-the so-called adipocytokines. Among adipocytokines, tumor
      necrotizing factor alpha, plasminogen activator inhibitor 1, and heparin-binding
      epidermal growth factor-like growth factor are produced in adipocytes as well as
      already known organs, and they contribute to the development of vascular
      diseases. Visfatin is a very recently discovered visceral fat-specific protein
      that may be related to the development of obesity-related diseases such as
      diabetes mellitus and cardiovascular disease. In contrast to these
      adipocytokines, adiponectin, also a newfound adipose tissue-specific collagen
      like protein, has been noted recently as an important antiatherogenic as well as
      antidiabetic protein. The function of adipocytokine secretion might be regulated
      dynamically by nutritional state. Visceral fat accumulation causes dysfunction of
      adipocytes including oversecretion of tumor necrotizing factor alpha, plasminogen
      activator inhibitor 1, and heparin-binding epidermal growth factor-like growth
      factor, as well as hyposecretion of adiponectin, which results in the development
      of a variety of metabolic and circulatory diseases. In this review, the
      importance of adipocytokines, including adiponectin, is discussed with respect to
      atherosclerosis.

PMID- 15968579
TI  - The role of dietary fat in obesity.
AB  - Current scientific evidence indicates that dietary fat plays a role in weight
      loss and maintenance. Meta-analyses of intervention trials find that fat-reduced
      diets cause a 3-4-kg larger weight loss than normal-fat diets. A 10% reduction in
      dietary fat can cause a 4-5-kg weight loss in individuals with initial body mass
      index of 30 kg m (-2). Short-term trials show that nonfat dietary components are
      equally important. Sugar-sweetened beverages promote weight gain, and replacement
      of energy from fat by sugar-sweetened beverages is counterproductive in diets
      aimed at weight loss. Protein has been shown to be more satiating than
      carbohydrate, and fat-reduced diets with a high protein content (20-25% of
      energy) may increase weight loss significantly. There is little evidence that low
      glycemic index foods facilitate weight control. Evidence linking certain fatty
      acids to body fatness is weak. Monounsaturated fatty acids may even be more
      fattening than polyunsaturated and saturated fats. No ad libitum dietary
      intervention study has shown that a normal-fat, high-monounsaturated fatty acid
      diet is comparable to a low-fat diet in preventing weight gain. Current evidence
      indicates that the best diet for prevention of weight gain, obesity, type 2
      diabetes, and cardiovascular disease is low in fat and sugar-rich beverages and
      high in carbohydrates, fiber, grains, and protein.

PMID- 15968580
TI  - Visceral fat as a determinant of fibrinolysis and hemostasis.
AB  - An increased amount of deep abdominal visceral fat has generally been accepted as
      an important cardiovascular risk factor, and disturbances in hemostasis and
      fibrinolysis have been suggested to play a role. Fibrinogen and von Willebrand
      factor, representatives of the hemostatic system, and plasminogen activator
      inhibitor 1 (PAI-1), as the most important inhibitor of the fibrinolytic system,
      have been associated with visceral obesity, with the most convincing evidence
      found for the involvement of PAI-1. The association with fibrinogen and von
      Willebrand factor has been suggested to be merely a reflection of the association
      with inflammation and endothelial dysfunction. The fact that PAI-1 is secreted by
      adipose tissue has attracted much attention. The increase of PAI-1 in visceral
      obesity could be because visceral adipose tissue produces more PAI-1 compared
      with subcutaneous abdominal adipose tissue. The contribution of other cell types
      such as hepatocytes or endothelial cells is probably more important, with
      stimulation of PAI-1 production by different components of the metabolic
      syndrome. PAI-1 secretion by adipose tissue has been suggested to have a more
      local effect, playing a role in tissue remodeling during the development of
      obesity.

PMID- 15968581
TI  - Obesity and endothelial dysfunction.
AB  - Obesity is becoming more prevalent in the developed world because of the
      abundance of food and the decrease of physical activity. Obesity is a risk factor
      for a host of diseases from arthritis to cardiovascular disease. The precise
      mechanisms by which obesity promotes cardiovascular disease are not well
      understood but are likely to include metabolic and inflammatory responses to the
      increased amount of stored fat. The endothelium plays a pivotal role in
      maintaining vascular health. Impaired endothelial function is an independent
      predictor of cardiovascular disease. Most studies of vascular function in obese
      subjects have demonstrated impaired endothelial function. This impairment of
      endothelial function becomes obvious early on, long before any vascular
      abnormalities become clinically relevant and detectable. Better understanding of
      the mediators of obesity-induced endothelial dysfunction may lead to the
      identification of new targets for interventions that may prevent or postpone the
      development of obesity-related cardiovascular disease.

PMID- 15968582
TI  - Origin and natural history of deep vein thrombosis of the legs.
AB  - Deep vein thrombosis (DVT) is a disorder frequently affecting the deep veins of
      the lower limbs; its onset is induced by known risk factors. The main
      complications of DVT are pulmonary embolism and postthrombotic syndrome (PST).
      Clinical pulmonary embolism occurs in a high proportion of cases of untreated
      proximal DVT and is associated with a mortality rate of 11-23% if not treated.
      PST, however, is a cause of increased morbidity and disability. The natural
      history of DVT is a dynamic process, with both thrombolysis and thrombus
      extension occurring after an episode of DVT. With the introduction of duplex
      scanning, several clinical studies have investigated and tried to clarify the
      natural history of DVT, the rate of recanalization of the thrombus, and the
      presence of reflux and its relation to lysis of the thrombus. These and other
      debated issues associated with PST are reviewed here. Knowledge of the evolution
      of these processes could result in better understanding of PST and be applied for
      improvement of medical and surgical management of venous thrombosis and its
      complications.

PMID- 15968583
TI  - Limb developmental stages of the newt Notophthalmus viridescens.
AB  - The current study consists of a detailed description of normal larval forelimb
      and hindlimb development in the newt, Notophthalmus viridescens. This is the
      first comprehensive record of staging limb development in this urodele amphibian
      species, augmenting Fankhauser's work which was published in fragments 60 years
      ago. Larvae were obtained by natural spawning, without hormone injections and
      while experimental conditions such as temperature and light cycles were kept
      constant (20 degrees C and 12L/12D), larval sizes have been added here merely as
      guidelines as development is influenced by a number of extrinsic factors. Care
      has been taken to indicate similarities to either the Harrison or Glucksohn
      stages, although this relates mainly to their morphological descriptions of the
      limbs. Observations from limb use are also mentioned in the text where pertinent
      to the description of development.

PMID- 15968584
TI  - Role of Jun N-terminal Kinase (JNK) signaling in the wound healing and
      regeneration of a Drosophila melanogaster wing imaginal disc.
AB  - When a fragment of a Drosophila imaginal disc is cultured in growth permissive
      conditions, it either regenerates the missing structures or duplicates the
      pattern present in the fragment. This kind of pattern regulation is known to be
      epimorphic, i.e. the new pattern is generated by proliferation in a specialized
      tissue called the blastema. Pattern regulation is accompanied by the healing of
      the cut surfaces restoring the continuous epithelia. Wound healing has been
      considered to be the inductive signal to commence regenerative cell divisions.
      Although the general outlines of the proliferation dynamics in a regenerating
      imaginal disc blastema have been well studied, little is known about the
      mechanisms driving cells into the regenerative cell cycles. In this study, we
      have investigated the role of Jun N-terminal Kinase (JNK) signaling in the wound
      healing and regeneration of a Drosophila wing imaginal disc. By utilizing in vivo
      and in vitro culturing of incised and fragmented discs, we have been able to
      visualize the dynamics in cellular architecture and gene expression involved in
      the healing and regeneration process. Our results directly show that homotypic
      wound healing is not a prerequisite for regenerative cell divisions. We also show
      that JNK signaling participates in imaginal disc wound healing and is regulated
      by the physical dynamics of the process, as well as in recruiting cells into the
      regenerative cell cycles. A model describing the determination of blastema size
      is discussed.

PMID- 15968585
TI  - The role of XTRAP-gamma in Xenopus pronephros development.
AB  - We isolated and characterized the Xenopus translocon-associated protein XTRAP
      gamma, one of four subunits of the translocon-associated protein complex. TRAP
      has been proposed to aid the translocation of nascent polypeptides into the lumen
      of the endoplasmic reticulum, but this has not been demonstrated until now. XTRAP
      gamma was specifically expressed in the pronephros tubules of Xenopus laevis from
      stage 25 during kidney development. Antisense morpholino oligonucleotide-mediated
      knockdown of XTRAP-gamma suppressed tubulogenesis and decreased expression of the
      pronephros marker genes Pax-2 and Wnt-4. XTRAP-gamma morpholinos also inhibited
      differentiation of the pronephros in activin/retinoic acid-treated animal caps.
      We conclude that XTRAP-gamma plays an important role in the process of pronephros
      differentiation.

PMID- 15968586
TI  - Chromosomal disorders and nuclear and cell destruction in cleaving human embryos.
AB  - Three types of defects of preimplantation embryogenesis contribute to the
      developmental arrest of cleaving human embryos: blastomere fragmentation,
      abnormal nuclear status and chromosomal disorders. Data concerning the relation
      and succession of these abnormalities during first mitotic cycles of the human
      zygote are controversial and mainly empirical at present. In this study we have
      performed simultaneous evaluation of blastomere fragmentation, nuclear apoptotic
      changes and the ploidy of four chromosomes (1, 5, 19 and X or 18, 21, X and Y) in
      193 human embryos. Another group of 28 embryos was subjected to TUNEL for
      confirmation of apoptosis in blastomere nuclei. Nuclei with apoptotic chromatin
      were seen in nearly 1/10 of blastomeres of embryos with good morphology and in
      more than 1/5 of blastomeres of embryos with more than 20% fragmentation. The
      correct number of investigated chromosomes was registered in 85.2% of
      successfully tested embryos. Chromatin apoptotic changes are the only limiting
      factor for the success of chromosomal FISH tests. Nearly 1/2 of embryos with at
      least one apoptotic nucleus were chromosomally abnormal. For the embryos that
      contain only normal nuclei, the rate of ploid normality was more than 89%. The
      rate of euploidy was higher (66%) in embryos with a significant degree of cell
      fragmentation. Moderate cell fragmentation was not related to significant
      increase of chromatin and chromosomal disorders. In a substantial portion of
      abnormal blastomeres, chromatin damage preceded cell fragmentation. Nuclear
      destruction in human blastomeres was illustrated by fluorograms of different
      stages of chromatin lesions.

PMID- 15968587
TI  - P450 aromatase expression in the temperature-sensitive sexual differentiation of
      salamander (Hynobius retardatus) gonads.
AB  - Sex differentiation of gonads in amphibians is believed to be controlled
      genetically, but altered epigenetically or environmentally. When larvae of the
      salamander Hynobius retardatus were reared at defined temperatures from hatching
      to metamorphic stages, a high temperature (28 degrees C) induced exclusively
      female gonads (ovaries), whereas intermediate (20 and 23 degrees C) or lower (16
      degrees C) temperatures produced a 1:1 sex ratio of the morphological gonads. The
      thermosensitive period was determined to be restricted from 15 to 30 days after
      hatching, just before or when sexual differentiation occurred. Hynobius P450
      aromatase (P450arom) cDNA was isolated from adult gonads and the partial
      nucleotide or deduced amino acid sequences were determined, showing a high level
      of identity with various vertebrate species. The P450arom gene was expressed
      predominantly in the adult ovary and brain, weakly in testis, but not in other
      somatic organs. A typical sexual dimorphism in P450arom expression was detected
      in normally developing larvae by a quantitative competitive RT-PCR; strong
      expression in the female gonads but very weak in male gonads. The dimorphism was
      detected much earlier than the morphological sexual differentiation of the
      gonads. When larvae were reared at the female-producing temperature (28 degrees
      C), strong expression was detected in all the temperature-treated larvae,
      suggesting that P450arom was up-regulated, even in genetic males. Our results
      confirm the importance of the P450arom regulation in the sexual differentiation
      of gonads and demonstrate that an up-regulation of P450arom is involved in the
      process of temperature-sensitive sex reversal in this species.

PMID- 15968588
TI  - Expression of csal1 in pre limb-bud chick embryos.
AB  - The spalt family of transcriptional repressors has been implicated in limb,
      heart, ear and kidney development and truncating mutations in a human gene,
      SALL1, result in the autosomal dominant disorder Townes-Brocks syndrome. Here we
      show the expression pattern of the chick orthologue of the SALL1 gene, csal1,
      during early development. We found csal1 expression in the heart and in the
      pharynx, a source of inductive signals during heart development. Expression was
      also seen in involuting mesoderm and later in presegmented paraxial mesoderm. We
      also describe expression in the ectoderm and neural plate of the early embryo and
      subsequent expression in the neural tube.

PMID- 15968589
TI  - Characterization of hypoxia induced gene 1: expression during rat central nervous
      system maturation and evidence of antisense RNA expression.
AB  - Although recent studies have provided a detailed understanding of cellular
      interactions occurring during the development of the CNS, little is known about
      the molecular signals which during the peri and postnatal periods ensure its
      maturation and functionality. Using the mammalian spinal cord as a model, we have
      designed experiments to examine the main changes in gene expression occurring
      during this critical transition. In this paper we describe the cloning and
      characterization of the rat hypoxia induced gene-1 (Hig-1), its expression
      pattern during spinal cord maturation and in situ localization of its mRNA. We
      show an increase in Hig-1 expression between P1 and P15 in the spinal cord and a
      differential spatial pattern. In the P1 spinal cord we observed preferential
      expression in regions of dorsal laminae II and III and laminae IX ventrally;
      while in P8, the distribution was more widespread and overall expression was
      increased. Hig-1 is also widely expressed in the brain. Results of in situ
      hybridization experiments, as well as particular features concerning ESTs, led us
      to propose the expression of an antisense mRNA. Primer-specific RTPCR
      demonstrates the presence of this aHig-1 transcript whose structure has not yet
      been characterized. The high homology between putative rHig-1 protein and human-
      and murine-predicted sequences, as well as its characteristic expression in the
      Central Nervous System, are indicative of a specific role which could be related
      to apoptosis signaling during postnatal maturation.

PMID- 15968590
TI  - Two members of the Fxr gene family, Fmr1 and Fxr1, are differentially expressed
      in Xenopus tropicalis.
AB  - The Fxr gene family is composed of three members, FMR1, FXR1 and FXR2. The FMR1
      gene is involved in the fragile X syndrome, whereas for the other two members, no
      human disorder has been identified yet. An appropriate animal model to study in
      vivo gene function is essential to unravel the cellular function of the gene
      products FMRP, FXR1P and FXR2P, respectively. In Xenopus tropicalis both Fmr1 and
      Fxr1 were identified; however, unexpectedly Fxr2 was not. Here we describe the
      characterization of both Fmrp and Fxr1p in Xenopus tropicalis. Fmrp is expressed
      ubiquitously throughout the embryo during embryonic development, whereas Fxr1p
      shows a more tissue-specific expression particularly during late embryonic
      development. In adult frogs both proteins are highly expressed in most neurons of
      the central nervous system and in all spermatogenic cells in the testis. In
      addition, Fxr1p is also highly expressed in striated muscle tissue. Western
      blotting experiments revealed only one prominent isoform for both proteins using
      different tissue homogenates from adult frogs. Thus, for in vivo gene function
      studies, this relative simple animal model may serve as a highly advantageous and
      complementary model.

PMID- 15968591
TI  - Genetic interaction of Gli3 and Alx4 during limb development.
AB  - The Gli3 and Alx4 transcriptional regulators are expressed in the anterior limb
      bud mesenchyme and their disruption in mice results in preaxial polydactyly.
      While the polydactylous phenotype of Alx4 deficient limb buds depends on SHH, the
      one of Gli3 deficient limb buds is completely independent of SHH signalling,
      suggesting that these genes act in parallel pathways. Analysis of limb buds
      lacking both Gli3 and Alx4 now shows that these two genes interact during limb
      skeletal morphogenesis. In addition to the defects in single mutants, the
      stylopod is severely malformed and the anterior element of the zeugopod is lost
      in double mutant limbs. However, limb bud patterning in Gli3-/-; Alx4-/- double
      mutant embryos is not affected more than in single mutants as the expression
      domains of key regulators remain the same. Most interestingly, the loss of the
      severe preaxial polydactyly characteristic of Gli3-/- limbs in double mutant
      embryos establishes that this type of polydactyly requires Alx4 function.

PMID- 15968593
TI  - The ultrastructure of mouse articular cartilage: collagen orientation and
      implications for tissue functionality. A polarised light and scanning electron
      microscope study and review.
AB  - Adult mouse articular cartilage (AC) has not been thoroughly described using high
      resolution imaging techniques, despite the fact that the availability of knockout
      mice with specific extracellular matrix (ECM) mutations have renewed interest in
      using the mouse as a model for a variety of different human conditions. With
      osteoarthritis affecting millions of people worldwide, investigations into the
      structure and, therefore, the ability of AC to act as a load-bearing tissue, are
      crucial for developing treatments and prevention techniques to limit the degree
      of severity in this condition. Cryofixation and formaldehyde fixation as well as
      chemical digestion of the uncalcified regions of AC were used in combination with
      bright field light, polarised light and scanning electron microscopy to image the
      structure of adult mouse AC. Chemical digestion of the tissue revealed unique
      insights into the structure of mouse AC and the high cellular density of the
      tissue. Tightly packed sheets of collagen fibrils formed the territorial matrix
      (TM) of the deep zone. These were observed closely surrounding the chondrons,
      after applying both chemical and cryofixation techniques. The interterritorial
      matrix (IM), in contrast, was more isotropically arranged. The results of the
      study have implications for the interpretation of biomechanical functionality of
      mouse AC with probable applications to other species.

PMID- 15968592
TI  - A mutation in SNAP29, coding for a SNARE protein involved in intracellular
      trafficking, causes a novel neurocutaneous syndrome characterized by cerebral
      dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma.
AB  - Neurocutaneous syndromes represent a vast, largely heterogeneous group of
      disorders characterized by neurological and dermatological manifestations,
      reflecting the common embryonic origin of epidermal and neural tissues. In the
      present report, we describe a novel neurocutaneous syndrome characterized by
      cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome).
      Using homozygosity mapping in two large families, we localized the disease gene
      to 22q11.2 and identified, in all patients, a 1-bp deletion in SNAP29, which
      codes for a SNARE protein involved in vesicle fusion. SNAP29 expression was
      decreased in the skin of the patients, resulting in abnormal maturation of
      lamellar granules and, as a consequence, in mislocation of epidermal lipids and
      proteases. These data underscore the importance of vesicle trafficking regulatory
      mechanisms for proper neuroectodermal differentiation.

PMID- 15968594
TI  - The hospital organization of the future.
AB  - The future of hospital Nuclear Medicine is triggered by the hospital organisation
      itself. In general, the hospital organisation of the present requires substantial
      changes in order to be competitive, economical, and abreast of the rapid
      progresses in medical developments and patient management. It also must be
      flexible to changes in health politics. In this special report an organisational
      hospital structure is outlined which may help encounter the challenging hospital
      future. Some hospitals have already implemented convincing changes, whereas
      others are far behind.

PMID- 15968595
TI  - (99m)Tc human IgG radiolabelled by HYNIC. Biodistribution and scintigraphy of
      experimentally induced inflammatory lesions in animal model.
AB  - BACKGROUND: Our goal was the efficient labelling of highly purified human
      gammaglobulin. This radioactive protein fraction can be used as a basic compound
      of radiopharmaceutical formulation for inflammation lesion diagnosis. This
      application was experimentally illustrated in animal models with artificially
      induced inflammatory lesions after turpentine oil injection into mouse leg
      muscle. MATERIALS AND METHODS: Hydrazine nicotinamine derivative of human
      gammaglobulin (IgG-HYNIC) was synthesized according to Abrams method. The
      radionuclide: technetium (99m)Tc has been introduced into protein molecules by
      indirect method incorporation in phosphate buffer, pH 7.4, in the presence of
      stannous chloride as a reducing agent for sodium pertechnetate, and EDTA as a
      coligand. Radiochemical purity was estimated by thin layer chromatography. The
      stability of labelled IgG-HYNIC derivative in human serum in presence of copper,
      cobalt, iron and manganum salts was analyzed by HPLC method (BioSEP SEC 4000,
      eluent: 0.1 mol/L phosphate). Inflammation lesions were induced in Balb/3 mice
      muscles by injection of 0.2 ml turpentine oil into the leg muscle. Five days
      later, inflammation lesions were visualized by hIgG-HYNIC- (99m)Tc injections.
      The tracer accumulation in tissue was evaluated by gamma camera at 1 to 24 hour
      intervals. RESULTS: Efficiency of technetium99m Tc human gammaglobulin labelling
      (pH 7.4, temp. 37 degrees C) was strictly dependant on ligand and coligand
      presence in the reaction mixture. Labelling of IgG molecules without any
      supplements resulted in very low efficiency, never exceeding the range of 5%.
      Presence of EDTA or hydrazine nicotinamide (HYNIC) conjugated with IgG increased
      radiolabelling efficiency to 50%. IgG-HYNIC derivative in EDTA presence enables
      us to reach value above 95% radiochemical purity. Stability of IgG-HYNIC
      derivative labelled with technetium (99m) Tc decreased rapidly in serum in time-
      up to 70% of initial value in 30 minutes and only 20% during further 4 hr
      incubation. This means that as much as 80% of radiotracer present in IgG
      molecules has been dissociated during incubation with serum. This forced us to
      find proper conditions for improving the stability of radioactive IgG-HYNIC
      conjugate in circulating serum for at least six hours. It was achieved by using a
      reaction medium supplement with divalent metal cations in the following
      compounds: MgCl2, CoSO4, Cu (NO3)2 and FeCl2 in equimolar ratio to EDTA.
      Scintigraphy of (99m)Tc gammaglobulin in artificially induced inflammatory
      lesions of mouse thigh muscle showed a 4 times higher accumulation of the tracer
      after 6 hours post injection, and 6 times higher after 24 hours. CONCLUSIONS: A
      human gammaglobulin derivative (hIgG-HYNIC) labelled with technetium (99m)Tc by
      indirect method with high radiochemical purity can be a basic compound of
      formulation for infection/inflammation scintigraphy.

PMID- 15968596
TI  - Marked survival prolongation of mice bearing a transplantable colon
      adenocarcinoma by treatment with radioactive platinum-[125I]histamine complex.
      Preliminary report.
AB  - BACKGROUND: Recently, a new PtCl2-histamine complex, and its radioactive
      analogues labelled with I-131 and I-125 have been synthesised and investigated
      both in vitro and in vivo. In this preliminary report the survival rate of
      radioactive platinum-[125I] histamine therapy in tumour-bearing mice is
      demonstrated. MATERIAL AND METHODS: A murine model of transplantable colon
      adenocarcinoma (C38) in C57BL/6 mice (15 days postimplantation) was used for the
      experiment. Three groups of animals were treated every 2-3 days with five
      intraperitoneal injections of the following preparations: PtCl2Hist (total dose
      of Pt--125 micromol/kg), PtCl2[125I]Hist (total dose of I-125--4.2 MBq; Pt--13
      micromol/kg), and "Active/Cold"--PtCl2[125I]Hist/PtCl2Hist (I-125--4.2 MBq; Pt-
      125 micromol/kg). A solution of 15% dimethylformamide in saline was applied to
      the control group. A survival analysis with the Kaplan-Meier estimation of
      survival curves and a statistical comparison by a log-rank test was applied to
      evaluate the anticancer activity of the tested preparations. RESULTS: Treatment
      of the animals with platinum-histamine preparations resulted in a significant
      prolongation of survivals, especially if the radioactive complex with carrier
      added PtCl2Hist (p < 0.005) was applied. The highest, almost a 60% prolongation
      of survival was observed in the Active/Cold group (MStr/MScon ratio = 1.58, 95%
      CI 1.22-1.93). For this group there was the lowest risk of death (hazard ratio HR
      = 0.29), whereas HR = 0.45 and 0.47 were found in the animals treated with
      unattended PtCl2Hist and 125I-labelled complex, respectively. CONCLUSION: The
      significant enhancement of in vivo anti-cancer activity by a concomitant
      combination of the therapeutic factors, i.e. cytotoxic/cytostatic activity of the
      platinum(II)-histamine and the Auger electrons effects generated by the attached
      I-125 radionuclide, was found on the murine model of transplantable colon
      adenocarcinoma.

PMID- 15968597
TI  - The value of estimating serum aproptotic marker concentrations in monitoring and
      prognosis of 131I--therapy in Graves' disease. Preliminary report.
AB  - BACKGROUND: The effect of radioiodine (131I) in Graves' disease (GD) is probably
      due to the direct physical destruction of thyrocytes by beta radiation, and by
      the indirect action through stimulation of apoptosis in these cells. The aim of
      our study was to investigate the changes in serum concentrations of sFas and
      sFasL as stimulators of apoptosis, and Bcl-2 as an inhibitor of apoptosis in
      patients with GD following 131I administration. MATERIAL AND METHODS: The study
      was performed on 30 patients with GD (29 female and 1 male aged 25-45). All
      patients were euthyroid (biochemical and clinical) prior to radioiodine therapy.
      The target absorbed dose ranged between 90 and 160 Gy. We assessed markers of
      apoptosis and hormone concentrations (fT3, fT4 and TSH) in the following manner:
      before 131I administration, then two weeks, one month, two, three, four, and five
      months after 131I administration. RESULTS: After four months, the concentrations
      of sFas and sFasL rose by 50% and decreased during the next month. Pretherapeutic
      concentrations of Bcl-2 were elevated, and peaked two weeks after ingestion,
      showing a gradual decrease with time. We found a significant increase in serum
      TSH, and a decrease of fT3 and fT4 concentrations by the end of the third month
      of radioiodine therapy. CONCLUSIONS: Decreases in serum levels of sFas and sFasL
      and increases of Bcl-2 are regarded as characteristic for GD patients before
      radioiodine therapy. Radioiodine therapy reverses the ratio of estimated markers
      after four months. The concentrations of hormones reflect actual thyroid
      function, whereas concentrations of markers of apoptosis may suggest
      morphological changes.

PMID- 15968598
TI  - Relationship between plasma BNP levels and left ventricular diastolic function as
      measured by radionuclide ventriculography in patients with coronary artery
      disease.
AB  - BACKGROUND: Radionuclide ventriculography enables such parameters of the left
      ventricular (LV) function as the ejection fraction (EF), ejection rate (ER) and
      filling rate (FR) to be measured correctly. The impairment of the LV function in
      coronary artery disease (CAD) results in an increase in plasma brain natriuretic
      peptide (BNP). The aim of this study was to check whether the reduction of the
      average filling rate (AFR) leads to an increase in plasma BNP levels in patients
      with CAD and nEF and whether that increase is comparable to that occurring in
      subjects with a reduced PER. MATERIAL AND METHODS: The study population comprised
      69 patients with CAD and 18 healthy subjects--a control group (CG). In all cases
      radionuclide ventriculography was performed at rest and the plasma BNP level was
      estimated. RESULTS: The plasma BNP concentration was significantly higher in the
      group with CAD than in those with CG . In patients with CAD and a decreased LVEF
      (dEF), the BNP level was significantly higher than in those with normal LVEF
      (nEF). In the subgroup with nEF and an AFR < or = 1.04 EDV/s, the level of plasma
      BNP was significantly higher than in that with an AFR >1.04. In the total CAD
      group, a significant correlation was found between plasma BNP concentrations and
      the LVEF, PER and AFR. In patients with nEF, the level of plasma BNP correlated
      only with the AFR. CONCLUSIONS: It is concluded that the diastolic dysfunction of
      the left ventricle in patients with CAD leads to an elevation of plasma BNP
      concentrations despite the normal ejection fraction. A diastolic dysfunction of
      the left ventricle affects the BNP plasma concentration to a greater degree than
      a systolic dysfunction.

PMID- 15968599
TI  - The prognostic value of dopamine receptor occupancy by [123I]IBZM-SPECT in
      schizophrenic patients treated with quetiapine.
AB  - BACKGROUND: In the present study D2 receptor occupancy was investigated in
      quetiapine treated schizophrenic patients for the detection of a relationship
      between the scintigraphic pattern and clinical signs and symptoms. MATERIAL AND
      METHODS: In 10 schizophrenic patients [123I]IBZM-SPECTs were performed during the
      introduction of quetiapine therapy (600-800 mg/day) and during a lower
      maintenance dose (200-400 mg/day). The patients' clinical follow-up was continued
      for 1 year. For the evaluation of SPECT images, visual interpretation was
      performed and striatum/occipital lobe (S/O) activity ratio was calculated.
      RESULTS: The initial striatum/occipital ratio was significantly higher in
      patients with relapse compared to the others (1.86 +/- 0.17, 1.53 +/- 0.15, p <
      0.01). The decreasing striatum/occipital ratio (increasing D2 receptor occupancy)
      on the 2nd SPECT was a predictive factor for the relapse. CONCLUSIONS: D2
      receptor occupancy and its changes during quetiapine therapy were related to the
      prognosis of the treatment efficacy.

PMID- 15968600
TI  - Assessment of clinical usefulness of 131I alpha-methyl-tyrosine and fused
      SPECT/MRI imaging for diagnostics of recurrent cerebral gliomas.
AB  - BACKGROUND: Early detection and diagnostic differentiation of neoplastic tissue
      from necrotic changes and scars following the treatment of cerebral gliomas is
      essential for determining further therapy and prognosis. The primary technique
      used for the diagnostics of recurrent neoplastic growth is the magnetic resonance
      imaging (MRI), which in some cases, however, does not allow one to identify the
      character of cerebral lesions. Recently, MRI has been supplemented with single
      photon emission computed tomography (SPECT) or positron emission tomography (PET)
      employing radiolabelled amino acids. e.g. tyrosine or methionine. The aim of the
      project was to assess the diagnostic potential of SPECT when iodine-131 alpha
      methyl tyrosine (IMT), a Polish make of radiopharmaceutical (OBRI--POLATOM,
      Otwock-Rwierk, Poland), was applied. The use of 131I as a substitute for the more
      costly, imported iodine-123 has been justified in view of the nature and
      significance of the diagnostic problem on the one hand, and the possibility of
      131-iodine application on a larger scale in CEE countries, on the other. MATERIAL
      AND METHODS: MRI and SPECT were performed in 24 patients with a history of
      surgical treatment and radiotherapy of cerebral glioma (WHO grade II/IV). A SPECT
      was carried out 15 min after an i.v. injection of 74-111 MBq IMT. The tomograms
      were evaluated visually and in quantitative terms. The fused SPET/MR images were
      also analyzed. The obtained results were verified against histopathological
      findings, control MRI examinations and the clinical course of disease within 7-28
      months of monitoring. RESULTS: In 19 patients, an increased IMT uptake indicative
      of a recurrent tumour was found, and the presence of the tumour was confirmed. In
      five patients no hot spots were detected which would indicate the neoplastic
      growth and verification did not provide any evidence for relapse. CONCLUSIONS:
      The examination employing iodine-131 IMT made it possible to confirm or exclude
      tumour recurrence in all the subjects, also in the cases when the CT/MR images
      were inconclusive. The MRI/SPECT fusion made it possible to more accurately
      identify the location of tumour recurrence as well as determine the area for
      spectroscopic MR analysis, for stereotactic biopsy and radiotherapy.

PMID- 15968601
TI  - A visual and semi-quantitative assessment of (99m)Tc-EDDA/HYNIC-TOC scintigraphy
      in differentiation of solitary pulmonary nodules.
AB  - BACKGROUND: The aim of the study was the assessment of the clinical usefulness of
      scintigraphy with (99m)Tc-EDDA/HYNIC-TOC for purposes of a differential diagnosis
      of SPNs by means of a visual inspection and semi-quantitative assessment of
      uptake intensity of the radiopharmaceutical (RPh). MATERIAL AND METHODS: In 53
      patients (32 males and 21 females at the ages between 38 and 78 years, mean value
      57) with SPN on chest radiographs or CT scans, of diameters from 1 to 5.5 (mean
      2.3) cm a SPECT acquisition was performed, 2-4 h after administration of 740 MBq
      of RPh. Additionally, aiming at the implementation of a correction of a partial
      volume effect resulting from finite resolution of this technique, the measurement
      of the resolution of this technique was performed on an thorax phantom.
      Scintigraphic studies were inspected visually visually and semi-quantitatively,
      restoring real concentration of the RPh in nodules in comparison with the
      peritumoral background (tumour-to-background ratio) by the application of
      resolution recovery coefficients for the respective nodule diameters. The
      threshold values of tumour-to-background ratio providing optimal differentiation
      between malignant and benign nodules of sizes smaller and larger than 2 cm in
      diameter were determined. Verification of scintigraphic results was based on
      pathological examinations of tumour samples (histopathology or cytology) and in
      some cases on bacteriological studies. The additional criterion of tumour
      benignity was accepted, based on its stable size in a time interval no shorter
      than 3 years. RESULTS: In 32 patients the following malignant tumours were
      diagnosed: 12 adenocarcinomas, 6 squamous cell carcinomas, 6 non-small cell lung
      cancers of unspecified more detailed morphology, 2 large cell carcinomas, 2 small
      cell lung cancers, 2 carcinoids and 2 metastatic lesions (malignant melanoma and
      leiomyosarcoma). In 21 patients benign etiologies were found: 6 tuberculomas, 2
      other granuloma, 4 hamartomas, 2 non-specific inflammatory infiltrate, 1 alien
      body with inflammatory reaction and 1 suppurating inflammatory lesion, 1
      abscesses, 1 peripheral carcinoid of morphological features of a benign tumour, 2
      tumours of unspecified etiology with sizes stable over 3 and 5 years, and 1
      ectopic lesion of thyroid tissue. A visual inspection of scintigrams revealed
      enhanced uptake of RPh at 29 of 32 sites corresponding to locations of malignant
      nodules, in 2 cases (1 adenocarcinoma and 1 metastatic lesion of malignant
      melanoma) results were negative and in 1 (metastatic leiomyosarcoma) equivocal;
      in 13 of 21 benign nodules true negative results were obtained, in 4--positive
      (foreign body with inflammatory reaction, abscess, suppurating inflammatory
      lesion and tuberculoma), in the next 4--equivocal (2 tuberculomas, 1 hamartoma, 1
      tumour of unspecified aetiology, but with a stable size over 3 years). The mean
      values of tumour-to-back-ground ratio without resolution recovery in malignant
      and benign nodules equalled 4.6 (sd 5.9) and 1.8 (sd 1.2), resp. (p = 7 x 10(
      4)), while after resolution recovery coefficients--7.8 (sd 7.2) and 2.7 (sd 2.8),
      resp. (p = 2 x 10(-4)). The semi-quantitative method resulted in true positive
      results in 29/32 malignant cases and true negative in 15/21 benign cases.
      CONCLUSIONS: (99m)Tc-EDDA/HYNIC-TOC scintigraphy is a very promising method for
      the differentiation of SPNs. The semi-quantitative method using resolution
      recovered tumour-to-background ratio enables the differentiation of malignant and
      benign SPNs based on the intensity of RPh uptake and facilitates the making of a
      decision as to the positive or negative scintigraphic character of the equivocal
      lesions.

PMID- 15968602
TI  - Technetium-99m-MIBI scintimammography by planar and SPECT imaging in the
      diagnosis of breast carcinoma and axillary lymph node involvement.
AB  - BACKGROUND: We compared SPECT and planar (99m)Tc-MIBI scintimammography (SMM) in
      the detection of primary breast cancer and metastatic axillary lymph node
      involvement, and the scintigraphic results with the histopathological/cytological
      findings. MATERIAL AND METHODS: 303 consecutive patients with 308 suspicious or
      indeterminate lesions observed in mammographies were entered in this study. After
      an intravenous injection of 740 MBq of (99m)Tc-MIBI, anterior supine, right and
      left lateral planar images in a prone position and a SPECT study were acquired.
      RESULTS: 85 malignant and 223 benign breast lesions were confirmed by
      histopathology/cytology. The overall sensitivity in the detection of breast
      cancer was 92% (78/85) for SPECT and 82% (70/85) for planar imaging (p = NS),
      respectively; overall specificity was 91% (204/223) for SPECT and 91% (202/223)
      for planar scans (p = NS), respectively. Metastatic axillary lymph node
      involvement was seen in 35 patients; per-axilla overall sensitivity was 66%
      (23/35) for SPECT and 54% (19/35) for planar images (NS), respectively; overall
      specificity was 76% (38/50) and 86% (43/50), respectively (NS). CONCLUSIONS: Our
      results confirm the high diagnostic accuracy of (99m)Tc-MIBI scintimammography in
      the diagnosis of breast cancer, and show SPECT to be slightly more sensitive than
      planar imaging, especially in detecting malignant breast lesions. We found the
      sensitivity of both imaging modalities to be quite low in the detection of
      metastatic axillary lymph node involvement. SPECT provides additional information
      to planar SMM with respect to the localization of (99m)Tc-MIBI uptake and tumour
      extent and improves diagnostic certainty. Our experience suggests that SPECT
      combined with planar SMM should be used more widely.

PMID- 15968603
TI  - Cortical scintigraphy in the evaluation of renal defects in children with vesico
      ureteral reflux--optimization of the procedure and study interpretation.
AB  - BACKGROUND: The objective of this study was to analyse the performance of several
      variants of kidney scintigraphy in children from the standpoint of: scar
      detection, an assessment of the rating of the pathology and an investigation of
      interobserver variability involved in the diagnostic procedure. MATERIAL AND
      METHODS: The analysis is based on results of a planar kidney scintigraphy and of
      a tomographic (SPECT) procedure. The latter was performed in two variants: 1) in
      which slices were obtained with axis of reconstruction identical with
      longitudinal axis of the body (SPECT I) and 2) in which axes were fitted to the
      long axis of each kidney separately (SPECT II). The rating of the diagnosed
      pathology was made using two scales, according to Goldraich and Howard.
      Evaluation of the images involved on the one hand, 150 individual kidneys and 75
      patients on the other. The assessment was made by three independent observers,
      differing in experience in nuclear medicine and employed in three independent
      departments. In the statistical analysis, as a measure of observer agreement, a
      proportion of agreeing readings (%) was accepted; in addition, the kappa index of
      agreement was calculated. RESULTS: Better agreement among three observers was
      attained when planar images were read in contrast to SPECT (I and II) results.
      The reading of SPECT II images yielded a higher frequency of diagnosed pathology
      (scars) in kidneys and is characterized by better overall agreement in detection
      by individual observers than a similar evaluation of SPECT I images. The
      Goldraich scale secures better interobserver agreement of renal scar detection
      than is seen when the Howard scale was applied to acquire the rating.
      CONCLUSIONS: The conclusion may be drawn that kidney scintigraphy is a method
      still burdened with a substantial subjectivism. Planar scintigraphy should be
      treated as a basic option for imaging post-inflammatory changes in kidneys.

PMID- 15968604
TI  - Screening for acute myocarditis--is scintigraphy with (99m)Tc-Anti-Granulocyte BW
      250/183 an answer?
AB  - BACKGROUND: Myocarditis is most often caused by Coxackie B virus, influenza
      viruses, and echoviruses. It is usually self-restricting and ending in full
      recovery, but in some patients the infection leads to congestive cardiomyopathy.
      It is difficult to identify patients with myocarditis using clinical criteria,
      laboratory tests, ECG and ultrasonography, and currently a myocardial biopsy is
      required to establish the diagnosis. The risk of complications, sampling error
      and costs of this procedure underline the need of non-invasive but sensitive
      methods of imaging. Several radiopharmaceuticals have been used so far to confirm
      inflammation: 67Ga, (99m)Tc-nanocolloids and 111In-leucocytes. Scintigraphy with
      radiolabeled autologous white blood cells (WBCs) is considered a very useful
      method in identifying sources of inflammation but is difficult to perform and
      time-consuming. AIMS: The aim of our study was to investigate whether
      scintigraphy with (99m)Tc-Anti-Granulocyte BW 250/183 antibody is a valuable
      diagnostic method in evaluating focal and diffuse inflammation of the heart and
      could therefore be suggested for use in screening for acute myocarditis. MATERIAL
      AND METHODS: A two dimensional scintigraphy and SPECT mode of heart imaging with
      the use of (99m)Tc-Anti-Granulocyte antibody (740 MBq) was performed on 14
      subjects (11 males and 3 females) aged 25-60 years with a positive myocardial
      biopsy confirming an inflammatory process in the myocardium. After i.v.
      administration of the tracer a 1 minute series of planar scans was performed
      within the first 60 minutes. Delayed static scans were performed at 1, 2, 4 and
      24 hours. RESULTS: The scintigraphic scans revealed the uptake of the tracer in
      the heart area in 13 patients, confirming active inflammatory process. Follow-up
      scintigraphy was performed 3-5 months after the first study, when the control
      myocardial biopsy was negative. The results of the study showed the concordance
      between myocardial biopsy and scintigraphy results in patients with an
      inflammatory process in the heart. CONCLUSIONS: Scintigraphy with the use of
      (99m)Tc-Anti-Granulocyte seems to be a useful diagnostic method in evaluating
      patients with suspected myocarditis, but further studies are needed to establish
      its sensitivity and specificity.

PMID- 15968605
TI  - Myocardial perfusion in women with systemic lupus erythomatosus and no symptoms
      of coronary artery disease.
AB  - BACKGROUND: The aim of the study was to assess myocardial perfusion in women with
      systemic lupus erythomatosus (SLE) and no symptoms of coronary artery disease
      (CAD). MATERIAL AND METHODS: Twenty two women with SLE of mean age 40.5 +/- 7.2
      were enrolled in the study. The average duration time of the disease was from 2
      to 19 years, mean 8 +/- 4.6 years. The inclusion criterion was the absence of
      stenocardial symptoms. The myocardial perfusion was studied by using Single
      Photon Emission Computerized Tomography (SPECT) utilising (99m)Tc-MIBI and a
      triple-head gamma-camera. We also analyzed risk factors of heart ischemic disease
      in our group. RESULTS: Myocardial perfusion stress scanning showed abnormal
      perfusion in 12 patients, 54.5% of the whole group, mostly in the anterior wall.
      At rest hypoperfusion abnormalities were found in 7 individuals. In patients with
      positive myocardial perfusion, out scanning, risk factors of CAD were more
      pronounced than in a sub-group with a negative result of myocardial perfusion
      scanning. CONCLUSIONS: In young women with SLE and no symptoms of coronary artery
      disease, myocardial perfusion defects may be detected by means of myocardial
      perfusion scintigraphy. Exercise and resting electrocardiography tests could be
      not sufficient for CAD diagnosis in women with SLE. The presence of coronary
      artery disease risk factors in women with SLE could be an indication to perform
      myocardial perfusion SPECT scanning.

PMID- 15968606
TI  - HENRE--Higher Education Network for Radiography in Europe.

PMID- 15968607
TI  - Veterinary nuclear medicine.

PMID- 15968608
TI  - Langerhans' cell histiocytosis of the mandible in bone scintigraphy and CT.
AB  - The authors present a case of a 4-year old boy with a quickly growing tumor of
      the jaw. The CT examination revealed a destructive tumor in the body of the
      mandible involving soft tissues. A diagnosis of eosinophilic granuloma of the
      mandible was confirmed by a biopsy of the tumor. Skeletal scintigraphy showed
      areas of increased and decreased radiotracer uptake. The fusion of CT and
      scintigraphy images showed that the "cold" focus corresponds with the osteolytic
      area and the "hot" focuses are larger than the areas of osseous reconstruction
      shown in CT. CONCLUSION: In cases of histiocytosis skeletal scintigraphy and CT
      are complementary methods that enable one to make an assessment of the extent of
      the disease.

PMID- 15968609
TI  - Lymphoscintigraphy in radical vaginal trachelectomy and pelvic lymphadenectomy.
AB  - BACKGROUND: Radical hysterectomy has traditionally been the treatment of choice
      for early invasive cervical carcinoma. Validation of the sentinel lymph node
      concept in gynaecology has led to less radical surgery. If preservation of
      fertility is an issue, then radical trachelectomy is an accepted approach. CASE
      REPORT: A 29-year-old female presented with stage IB1 cervical cancer was treated
      by radical vaginal trachelectomy and pelvic lymphadenectomy as definitive
      treatment. Two obturator nodes visualised on lymphoscintigraphy and one
      parametrial not visualized on lymphoscintigraphy were "hot" and blue during
      surgery, and identified as sentinel nodes. All 18 nodes were non-metastatic.
      CONCLUSION: Preoperative lymphoscintigraphy is a useful tool in the preoperative
      localisation of sentinel lymph nodes, and should be undertaken in cases of early
      invasive cervical carcinoma where a radical trachelectomy is performed to
      preserve fertility.

PMID- 15968610
TI  - (99m)Tc-MDP uptake in soft-tissue osteosarcoma in a dog.

PMID- 15968612
TI  - Czech Society of Nuclear Medicine, XLI Days of Nuclear Medicine, October 7-9,
      2004, Hradec na Moravici, Czech Republic.

PMID- 15968613
TI  - 12th European Symposium on Radiopharmacy and Radiopharmaceuticals, September 9
      11, 2004, Gdansk-Sopot, Poland.

PMID- 15968614
TI  - Higher Education Network for Radiography in Europe--annual general meeting,
      October 27-31, 2004, Marsascala, Malta.

PMID- 15968615
TI  - 11th Meeting of the Berlin-Brandenburg Society of Nuclear Medicine, 29-30
      October, 2004, Potsdam, Germany.

PMID- 15968616
TI  - Targeted Radiotherapy with Alpha-Particle Emitting Radionuclides Seminar,
      November 18, 2004, Cracow, Poland.

PMID- 15968617
TI  - A window on Serbia and Montenegro.

PMID- 15968622
TI  - Prenatal imaging of limb-body wall complex by magnetic resonance imaging.

PMID- 15968623
TI  - Fetal nasal bone and trisomy 21 in the second trimester.
AB  - OBJECTIVES: To assess the feasibility of measuring nasal bone length in the
      second trimester of pregnancy and to confirm if fetal nasal bone absence or
      hypoplasia is a marker for Down syndrome. METHODS: Fetal nasal bone assessment
      was performed in 439 consecutive singleton pregnancies at high risk of Down
      syndrome between 15 and 21 weeks. All ultrasound examinations were performed
      transabdominally by five skilled sonographers. If the nasal bone was present, its
      length was measured. The biparietal diameter: nasal bone length ratio (BPD/NBL)
      was also calculated. RESULTS: Nasal bone assessment was successfully achieved in
      all fetuses. The nasal bone was absent in 2(0.47%) of the 417 unaffected fetuses
      and in 10(55.5%) of the 18 fetuses with trisomy 21. Of the 8 Down syndrome cases
      with a nasal bone present, 4 had nasal bone hypoplasia and 4 had a normal nasal
      bone. BPD/NBL was 9 or greater in 7 of the 8 fetuses affected by trisomy 21 with
      nasal bone present and in 86 (20.6%) of the 417 normal fetuses; it was 10 or
      greater in 5 of the 8 (62.5%) fetuses affected by trisomy 21 and in 41 of the 417
      (9.8%) euploid fetuses. CONCLUSIONS: Nasal bone absence is a marker for Down
      syndrome in the second trimester of pregnancy. Inclusion of nasal bone length
      into the second-trimester screening protocol could potentially obviate the false
      negative cases from other screening tests. The measurement of nasal bone length
      in the second trimester seems to provide additional benefits beyond the
      assessment of the presence or absence of the nasal bone.

PMID- 15968624
TI  - The synthesis of oligomers of oxetane-based dipeptide isosteres derived from L
      rhamnose or D-xylose.
AB  - Routes to oligomers (dimers, tetramers, hexamers) of five oxetane-based dipeptide
      isosteres have been established. Methyl 2,4-anhydro-5-azido-5-deoxy-L-rhamnonate
      'monomer' led, by coupling the corresponding carboxylic acid and amine, to a
      'dimer'. Reverse-aldol ring-opening occurred on attempted saponification of the
      dimer, so all further oligomerization was performed using TBDMS C-3 hydroxyl
      protection. The silyl protected L-rhamnonate monomer led in turn to the dimer
      (via the monomer acid and amine), the tetramer (via the dimer acid and amine) and
      finally the hexamer (via the tetramer acid and dimer amine). In each case the
      acids were obtained through saponification of the respective methyl esters and
      the amines were obtained by hydrogenation of the azides; coupling was TBTU
      mediated. Essentially the same strategy was employed on equivalent D-lyxonate, 6
      deoxy-L-altronate, 6-deoxy-D-gulonate and D-fuconate dipeptide isosteres to give
      the respective dimers, tetramers and hexamers.

PMID- 15968625
TI  - Maternal diet alters exencephaly frequency in SELH/Bc strain mouse embryos.
AB  - BACKGROUND: The SELH/Bc mouse inbred strain, with a high frequency of
      nonsyndromic, genetically-multifactorial exencephaly, is a model for human
      cranial neural tube defects (NTDs). Maternal diet affects risk of human NTDs.
      METHODS: Exencephaly frequencies in SELH/Bc embryos were compared in 8 studies in
      which dams were fed alternative commercial Purina diets (5015 and 5001) or
      semisynthetic diets, and in several studies in which maternal diet was
      supplemented with a specific nutrient, either in drinking water or food before
      and during pregnancy, or by intraperitoneal injection on E7 and/or E8. RESULTS:
      The exencephaly frequency in SELH/Bc embryos was 2- to 8-fold higher when the
      dams were fed Purina 5015 (averaging 23% exencephaly) or a semisynthetic diet
      modeled on Purina 5015 (averaging 28%) or NIH-31 standard diet (23%), compared
      with Purina 5001 (averaging 7%). The exencephaly frequency remained high (41%) on
      a semisynthetic diet modeled on Purina 5001. The exencephaly frequency was not
      reduced significantly by maternal supplementation with folic acid, nor with each
      of zinc, methionine, niacin, brewers' yeast, riboflavin, vitamin B12, or
      inositol. Nor was it reduced by maternal diets with supplemental methyl donors
      and cofactors or with reduced fat. CONCLUSIONS: The frequency of exencephaly in
      SELH/Bc embryos is strongly influenced by a specific unidentified aspect of the
      commercial ration Purina 5001 that prevents 55-85% of exencephaly in SELH/Bc
      embryos, when directly compared with an alternative commercial ration Purina 5015
      or its semisynthetic mimic. This strong maternal diet effect on NTD frequency may
      point to novel nutritional approaches to prevention of human NTDs.

PMID- 15968626
TI  - Effects of D-glucose concentration, D-fructose, and inhibitors of enzymes of the
      pentose phosphate pathway on the development and sex ratio of bovine blastocysts.
AB  - D-glucose at 5.6 mM reduces the progression of in vitro-produced (IVP) bovine
      embryos from the morula to the blastocyst stage and skews sex ratio towards
      males. Possibly, the presence of two transcriptionally active X-chromosomes
      compromises female embryo development through imbalance in glucose metabolism.
      Here, we have determined the threshold of embryo sensitivity to glucose, whether
      substitution of D-fructose for glucose reduces the selective loss of female
      embryos, and whether inhibition of an X-linked gene product, glucose 6-phosphate
      dehydrogenase (G6PD), normalizes sex ratio among bovine blastocysts. IVP zygotes
      were cultured in glucose-free medium to 72 hr post-insemination, at which time 8
      cell embryos were selected for treatment and cultured until 144 hr post
      insemination. Addition of 4 mM glucose at the 8-cell stage reduced (P < 0.05) the
      number of blastocyst that formed, whereas 2.5 and 1 mM glucose had no effect. Sex
      ratio in the presence of 4 and 2.5 mM glucose differed significantly from 0.5,
      while 1 mM glucose had no effect. D-fructose (5.6 mM) did not compromise
      development to blastocyst and did not alter the sex ratio of blastocysts that
      formed. When G6PD inhibitors (dehydroepiandrosterone: DHEA and 6
      aminonicotinamide: 6-AN), which effectively inhibit the reduction of the NADPH
      sensitive dye, brilliant cresyl blue (BCB) in bovine morulae, were added to the
      culture medium containing 4 mM glucose, embryo development was moderately
      reduced, but sex ratio skewing was corrected (with 6-AN) or lowered (with DHEA).
      In conclusion, glucose above 2.5 mM impairs bovine embryo development and
      increases sex ratio, most likely as a result of increased pentose-phosphate (PP)
      pathway activity in female embryos.

PMID- 15968627
TI  - Vitrification of calf oocytes: effects of maturation stage and prematuration
      treatment on the nuclear and cytoskeletal components of oocytes and their
      subsequent development.
AB  - This study was designed to establish the effects of the meiotic stage of bovine
      oocytes and of a prematuration treatment with roscovitine (ROS) on their
      resistance to cryopreservation. Oocytes from prepubertal calves at the stages of
      germinal vesicle breakdown (GVBD) or at metaphase II (MII) were vitrified by the
      open pulled straw (OPS) method. In another experiment, oocytes were kept under
      meiotic arrest with 50 microM ROS for 24 hr and vitrified at the GVBD stage.
      After warming, some oocyte samples were fixed, stained using specific fluorescent
      probes and examined under a confocal microscope. The remaining oocytes were
      fertilized, and cleavage and blastocyst rates recorded. Significantly lower
      cleavage rates were obtained for the vitrified GVBD and MII oocytes (9.9% and
      12.6%, respectively) compared to control oocytes (73.9%). Significantly worse
      results in terms of cleavage rates were obtained when GVBD calf oocytes were
      exposed to cryoprotectants (CPAs: ethylene glycol plus dimethyl sulfoxide, DMSO)
      (13.1%) or vitrified (1.6%) after a prematuration treatment with ROS, when
      compared to untreated control oocytes (68.7%) or ROS-control oocytes (56.6%).
      None of the vitrification procedures yielded blastocysts, irrespective of the
      initial meiotic stage or previous prematuration treatment. Compared to the
      control oocytes, significantly fewer oocytes exhibited normal spindle
      configuration after being exposed to CPAs or after vitrification of either GVBD
      or MII calf oocytes. These results indicate that the vitrification protocol has a
      deleterious effect on the meiotic spindle organization of calf oocytes
      cryopreserved at both the GVBD and MII stage, which impairs the capacity for
      further development of the embryos derived from these vitrified oocytes.
      Prematuration treatment with ROS has no beneficial effect on the outcome of
      vitrification by the OPS method.

PMID- 15968628
TI  - Rapid and reactive nitric oxide production by astrocytes in mouse neocortical
      slices.
AB  - Nitric oxide (NO), a cellular signaling molecule, is produced in the brain by
      both neurons and astrocytes. While neurons are capable of rapid release of small
      amounts of NO serving as neurotransmitter, astrocytic NO production has been
      demonstrated mainly as a slow reaction to various stress stimuli. Little is known
      about the role of astrocyte-produced NO. Using the NO indicator 4,5
      diaminofluorescein-2 diacetate (DAF-2DA) and acute slices from mouse brain, we
      distinguished neurons from astrocytes based on their different fluorescence
      kinetics and pattern, cellular morphology, electrophysiology, and responses to
      selective nitric oxide synthase (NOS) inhibitors. Typically, astrocytic
      fluorescence followed neuronal fluorescence with a delay of 1-2 min and was
      dependent on the inducible NOS isoform (iNOS) activity. Western blot analysis
      established the presence of functional iNOS in the neocortex. An assay for cell
      death revealed that most DAF-2DA-positive neurons, but not astrocytes, were
      damaged. Whole cell recordings from astrocytes confirmed that these cells
      maintained their membrane potential and passive properties during illumination
      and afterward. Induction of excitotoxicity by brief application of glutamate
      triggered an immediate and intense astrocytic response, while high-frequency
      electrical stimulation failed to do so. The present study demonstrates, for the
      first time, rapid and massive iNOS-dependent NO production by astrocytes in situ,
      which appears to be triggered by acute neuronal death. These data may bear
      important implications for our theoretical understanding and practical management
      of acute brain insults.

PMID- 15968629
TI  - Anti-disialosyl antibodies mediate selective neuronal or Schwann cell injury at
      mouse neuromuscular junctions.
AB  - The human paralytic neuropathy, Miller Fisher syndrome (MFS) is associated with
      autoantibodies specific for disialosyl epitopes on gangliosides GQ1b, GT1a, and
      GD3. Since these gangliosides are enriched in synaptic membranes, anti
      ganglioside antibodies may target neuromuscular junctions (NMJs), thereby
      contributing to disease symptoms. We have shown previously that at murine NMJs,
      anti-disialosyl antibodies induce an alpha-latrotoxin-like effect,
      electrophysiologically characterized by transient massive increase of spontaneous
      neurotransmitter release followed by block of evoked release, resulting in
      paralysis of the muscle preparation. Morphologically, motor nerve terminal
      damage, as well as perisynaptic Schwann cell (pSC) death is observed. The
      relative contributions of neuronal and pSC injury to the paralytic effect and
      subsequent repair are unknown. In this study, we have examined the ability of
      subsets of anti-disialosyl antibodies to discriminate between the neuronal and
      glial elements of the NMJ and thereby induce either neuronal injury or pSC death.
      Most antibodies reactive with GD3 induced pSC death, whereas antibody reactivity
      with GT1a correlated with the extent of nerve terminal injury. Motor nerve
      terminal injury resulted in massive uncontrolled exocytosis with paralysis.
      However, pSC ablation induced no acute (within 1 h) electrophysiological or
      morphological changes to the underlying nerve terminal. These data suggest that
      at mammalian NMJs, acute pSC injury or ablation has no major deleterious
      influence on synapse function. Our studies provide evidence for highly selective
      targeting of mammalian NMJ membranes, based on ganglioside composition, that can
      be exploited for examining axonal-glial interactions both in disease states and
      in normal NMJ homeostasis.

PMID- 15968630
TI  - Oligodendrocyte-specific ceramide galactosyltransferase (CGT) expression
      phenotypically rescues CGT-deficient mice and demonstrates that CGT activity does
      not limit brain galactosylceramide level.
AB  - Galactosylceramide (GalC) is the major sphingolipid of the myelin membrane. Mice
      lacking GalC due to ceramide galactosyltransferase (CGT) deficiency form unstable
      and functionally affected myelin and exhibit a progressive demyelination,
      accompanied by severe motor coordination deficits. In addition to
      oligodendrocytes, CGT is also expressed in other cells, e.g., neurons and
      astrocytes. We examined the possibility that lack of CGT in these cells
      contributes to the phenotype of CGT-deficient mice. Toward this aim, we generated
      transgenic mice expressing CGT under the control of oligodendrocyte-specific
      proteolipid protein (PLP) promoter and examined the possibility of a transgenic
      rescue of CGT-deficient mice. CGT-deficient mice expressing the PLP-CGT transgene
      did not show any behavioral abnormalities, normal myelin structure, and MBP
      levels. CGT activity as well as GalC and sulfatide levels of rescued mice were
      not significantly different from wild-type controls. Thus, transgenic rescue with
      the PLP-CGT transgene was apparently complete. In contrast to wild-type and
      rescued mice, PLP-CGT transgenic mice on a wild-type background exhibited
      significantly elevated CGT activity which directly correlated with an increase in
      non-hydroxy fatty acid (NFA)-GalC, but not alpha-hydroxy fatty acid (HFA)-GalC.
      HFA-GalC decreased in adult transgenic mice, indicating that NFA-GalC, but not
      HFA-GalC levels are limited by CGT activity. As a consequence, the total amount
      of GalC is unchanged over a rather wide range of CGT expression levels in the
      mouse brain. Our results indicate that loss of CGT in oligodendrocytes is
      exclusively responsible for the myelin structural deficits, demyelination, and
      behavioral abnormalities in CGT-deficient mice.

PMID- 15968632
TI  - Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by
      astrocytes.
AB  - After injury to the adult central nervous system (CNS), numerous cytokines and
      growth factors are released that contribute to reactive gliosis and extracellular
      matrix production. In vitro examination of these cytokines revealed that the
      presence of transforming growth factor-beta1 (TGF-beta1) and epidermal growth
      factor (EGF) greatly increased the production of several chondroitin sulfate
      proteoglycans (CSPG) by astrocytes. Treatment of astrocytes with other EGF
      receptor (ErbB1) ligands, such as TGF-alpha and HB-EGF, produced increases in
      CSPG production similar to those observed with EGF. Treatment of astrocytes,
      however, with heregulin, which signals through other members of the EGF-receptor
      family (ErbB2, ErbB3, ErbB4), did not induce CSPG upregulation. The specificity
      of activation through the ErbB1 receptor was further verified by using a
      selective antagonist (AG1478) to this tyrosine kinase receptor. Western blot
      analysis of astrocyte supernatant pre-digested with chondroitinase ABC indicated
      the presence of multiple core proteins containing 4-sulfated or 6-sulfated
      chondroitin. To identify some of these CSPGs, Western blots were screened using
      antibodies to several known CSPG core proteins. These analyses showed that
      treatment of astrocytes with EGF increased phosphacan expression, whereas
      treatment with TGF-beta1 increased neurocan expression. Reverse transcription
      polymerase chain reaction (RT-PCR) was used to examine the expression of these
      molecules in vivo, which result in increased expression of TGF-beta1, EGF
      receptor, neurocan, and phosphacan after injury to the brain. These data begin to
      elucidate some of the injury-induced growth factors that regulate the expression
      of CSPGs which could be targeted in the future to modulate CSPG production after
      injury to the central nervous system.

PMID- 15968633
TI  - Oligodendrocyte-myelin glycoprotein is present in lipid rafts and caveolin-1
      enriched membranes.
AB  - The oligodendrocyte-myelin glycoprotein is a ligand of the neuronal Nogo receptor
      and a potent inhibitor of neurite outgrowth, but its physiological function
      remains to be elucidated. The oligodendrocyte-myelin glycoprotein is anchored
      solely in the outer leaflet of the plasma membrane via its
      glycosylphosphatidylinositol anchor, and through its leucine-rich repeat domain,
      it likely interacts with other proteins. In the present study, we compare its
      buoyancy and detergent solubility characteristics with those of other myelin
      proteins. Based on its detergent solubility profile and membrane fractionation
      using established ultracentrifugation procedures, we conclude that the
      oligodendrocyte-myelin glycoprotein is a lipid raft component that is closely
      associated with the axolemma. Moreover, it associates with caveolin-1 and
      caveolin-1-enriched membranes. We postulate that, by virtue of its concentration
      in lipid rafts and perhaps through interactions with caveolin-1, the
      oligodendrocyte-myelin glycoprotein may influence signaling pathways.

PMID- 15968631
TI  - Cytokine toxicity to oligodendrocyte precursors is mediated by iron.
AB  - Inflammatory processes play a key role in the pathogenesis of a number of common
      neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease
      (PD), and multiple sclerosis (MS). Abnormal iron accumulation is frequently noted
      in these diseases and compelling evidence exists that iron is involved in
      inflammatory reactions. Histochemical stains for iron repeatedly demonstrate that
      oligodendrocytes, under normal conditions, stain more prominently than any other
      cell type in the brain. Therefore, we examined the hypothesis that cytokine
      toxicity to oligodendrocytes is iron mediated. Oligodendrocytes in culture were
      exposed to interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor
      necrosis factor-alpha (TNF-alpha). Toxicity was observed in a dose-dependent
      manner for IFN-gamma and TNF-alpha. IL-1beta was not toxic in the concentrations
      used in this study. The toxic concentration of IFN-gamma, and TNF-alpha was lower
      if the cells were iron loaded, but iron loading had no effect on the toxicity of
      IL-1beta. These data provide insight into the controversy regarding the toxicity
      of cytokines to oligodendrocytes by revealing that iron status of these cells
      will significantly impact the outcome of cytokine treatment. The exposure of
      oligodendrocytes to cytokines plus iron decreased mitochondrial membrane
      potential but activation of caspase 3 is limited. The antioxidant, TPPB, which
      targets mitochondria, protected the oligodendrocytes from the iron-mediated
      cytotoxicity, providing further support that mitochondrial dysfunction may
      underlie the iron-mediated cytokine toxicity. Therapeutic strategies involving
      anti-inflammatory agents have met with limited success in the treatment of
      demyelinating disorders. A better understanding of these agents and the
      contribution of cellular iron status to cytokine toxicity may help develop a more
      consistent intervention strategy.

PMID- 15968634
TI  - Astrocytes in the arcuate nucleus and median eminence that take up a fluorescent
      dye from the circulation express leptin receptors and neuropeptide Y Y1
      receptors.
AB  - Following systemic injection, several different dyes and markers are found to
      accumulate rapidly in cells in the arcuate nucleus and median eminence, and the
      capillaries in this region appear specialised for exchange of molecules. The
      present study used hydroxystilbamidine (FluoroGold equivalent) to identify cells
      that take up molecules from the circulation in these regions; 2-6 h following
      injection, uptake was seen in the external and intermediate zones of the median
      eminence and the adjacent ventral part of the arcuate nucleus, but not in other
      regions of the hypothalamus. The labelled cells were small; double-labelling
      experiments revealed that they expressed glial fibrillary acid protein (GFAP),
      but not NeuN, Agouti-related protein (AgRP) or beta-endorphin. They had the
      morphology of astrocytes and were readily distinguished from tanycytes by
      staining for vimentin. Many of these labelled astrocytes also expressed leptin
      receptors and neuropeptide Y Y1 receptors. The surrounding neurons that expressed
      these receptors did not take up this dye. This demonstrates that astrocytes take
      up molecules from the circulation in the median eminence and adjacent arcuate
      nucleus, and may have a significant signalling role in regulation of food intake.

PMID- 15968635
TI  - Expression of P0 glycoprotein in CNS glia: effects of overexpression in N20.1
      cells.
AB  - To examine effects of expression of the PNS myelin P0 glycoprotein in glial cells
      of CNS lineage, we transfected murine N20.1 glial cells with a rat P0 cDNA. A
      stably transfected cell line expressing high levels of P0 message showed P0
      immunostaining, along with changes in morphology. Polymerase chain reaction (PCR)
      identified the predicted rat P0 sequence in the transfected N20.1 cells and
      further revealed low levels of mouse P0 message in the nontransfected cells and
      in primary mouse astrocytes. This is the first evidence of endogenous expression
      of message for P0 glycoprotein in CNS glia. Quantitative RT-PCR confirmed the
      expression of rat P0 mRNA in the transfected N20.1 cells, at levels about 400
      times greater than murine P0 in nontransfected cells. A 27-kD band was detected
      in the transfected cells by Western blot with P0 antibody, but not in mock
      transfected or nontransfected N20.1 cells. Immunocytochemistry following
      permeabilization showed intracellular vesicular localization of P0 in the
      cytoplasm and perinuclear rings in transfected cells, with a similar pattern but
      much lower levels in nontransfected cells. Faint surface staining for P0 protein
      without permeabilization was seen only on the transfected cells. A few
      transfected cells with membrane sheets stained more intensely for surface P0.
      Quantitative RT-PCR was used to determine if P0 overexpression altered expression
      of other myelin-related genes compared with glial fibrillary acidic protein
      (GFAP); the ratios of myelin basic protein (MBP)/GFAP and proteolipid protein
      (PLP)/GFAP were increased 2- to 3-fold in the P0-transfected cells. We conclude
      that P0 overexpression alters N20.1 gene expression and cell morphology, and
      shifts the cells from astroglial to oligodendroglial phenotype.

PMID- 15968636
TI  - Olfactory ensheathing cells and olfactory nerve fibroblasts maintain continuous
      open channels for regrowth of olfactory nerve fibres.
AB  - The ensheathing cells of the olfactory nerves are arranged end-to-end to form a
      continuous channel enclosing the olfactory axons from their origin in the
      olfactory mucosa to their termination in the olfactory bulb. On their outer
      surface, the olfactory ensheathing cell channels have a basal lamina and an outer
      encirclement of olfactory nerve fibroblasts. We present an anatomical model of
      the ensheathing arrangements for the entire transit of the olfactory axons from
      the horizontal basal cells of the mucosa through the nerves to the superficial
      astrocytes of the bulb. We used intracranial section of the olfactory nerves to
      induce a rapid retrograde loss of olfactory neurons and degeneration of their
      axons, followed by replacement of the neurons from stem cells in the mucosa and
      growth of the newly formed axons along the olfactory nerves. The olfactory
      ensheathing cells survive and play a vital role in this process. Unlike Schwann
      cells in damaged peripheral nerve, the olfactory ensheathing cells neither divide
      nor migrate. They are actively phagocytic for removal of the degenerating axons,
      and provide continuous stable open channels along which adventitious cells such
      as erythrocytes and macrophages can travel, and along which the newly formed
      axons can regenerate. We suggest that the persistence of these open channels is
      an important element in the effectiveness of the regeneration. These properties,
      which the olfactory ensheathing cells exert in collaboration with olfactory nerve
      fibroblasts, may also be involved in the reparative effects of these cells when
      transplanted into lesions of the spinal cord.

PMID- 15968638
TI  - Microrobotics and MEMS-based fabrication techniques for scaffold-based tissue
      engineering.
AB  - Scaffold based tissue engineering strategies use cells, biomolecules and a
      scaffold to promote the repair and regeneration of tissues. Although scaffold
      based tissue engineering approaches are being actively developed, most are still
      experimental, and it is not yet clear what defines an ideal scaffold/cell
      construct. Solid free form fabrication (SFF) techniques can precisely control
      matrix architecture (size, shape, interconnectivity, branching, geometry and
      orientation). The SFF methods enable the fabrication of scaffolds with various
      designs and material compositions, thus providing a control of mechanical
      properties, biological effects and degradation kinetics. This paper reviews the
      application of micro-robotics and MEMS-based fabrication techniques for scaffold
      design and fabrication. It also presents a novel robotic technique to fabricate
      scaffold/cell constructs for tissue engineering by the assembly of microscopic
      building blocks.

PMID- 15968639
TI  - The fate of human malignant melanoma cells transplanted into zebrafish embryos:
      assessment of migration and cell division in the absence of tumor formation.
AB  - Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype,
      expressing genes that are characteristic of various cell types including
      endothelial, neural, and stem cells. Moreover, we have shown that aggressive
      melanoma cells can participate in neovascularization in vivo and vasculogenic
      mimicry in vitro, demonstrating that these cells respond to microenvironmental
      cues and manifest developmental plasticity. To explore this plasticity further,
      we transplanted human metastatic melanoma cells into zebrafish blastula-stage
      embryos and monitored their behavior post-transplantation. The data show that
      human metastatic melanoma cells placed in the zebrafish embryo survive, exhibit
      motility, and divide. The melanoma cells do not form tumors nor integrate into
      host organs, but instead become scattered throughout the embryo in interstitial
      spaces, reflecting the dedifferentiated state of the cancer cells. In contrast to
      the fate of melanoma cells, human melanocytes transplanted into zebrafish embryos
      most frequently become distributed to their normal microenvironment of the skin,
      revealing that the zebrafish embryo contains possible homing cues that can be
      interpreted by normal human cells. Finally, we show that within the zebrafish
      embryo, metastatic melanoma cells retain their dedifferentiated phenotype. These
      results demonstrate the utility of the zebrafish embryonic model for the study of
      tumor cell plasticity and suggest that this experimental paradigm can be a
      powerful one in which to investigate tumor-microenvironment interactions.

PMID- 15968640
TI  - Agonists for the peroxisome proliferator-activated receptor-alpha and the
      retinoid X receptor inhibit inflammatory responses of microglia.
AB  - The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) plays a key
      role in lipid metabolism and inflammation. Recently, we demonstrated that
      administration of the PPAR-alpha agonists gemfibrozil and fenofibrate, inhibit
      the clinical signs of experimental autoimmune encephalomyelitis (EAE), the animal
      model of multiple sclerosis (MS). In the present study we investigated the
      effects of PPAR-alpha agonists on primary mouse microglia, a cell type implicated
      in the pathology of MS and EAE. Our studies demonstrated that the PPAR-alpha
      agonists ciprofibrate, fenofibrate, gemfibrozil, and WY 14,643 each inhibited NO
      production by cytokine-stimulated microglia in a dose-dependent manner. However,
      fenofibrate and WY 14,643 were more potent inhibitors than gemfibrozil and
      ciprofibrate. In LPS-stimulated microglia, only fenofibrate and WY 14,643
      significantly suppressed NO production. Additionally, PPAR-alpha agonists
      inhibited the secretion of the proinflammatory cytokines IL-1beta, TNF-alpha, IL
      6, and IL-12 p40 and the chemokine MCP-1 by LPS-stimulated microglia. Retinoid X
      receptors (RXRs) physically interact with PPAR-alpha receptors, and the resulting
      heterodimers regulate the expression of PPAR-responsive genes. Interestingly, the
      RXR agonist 9-cis retinoic acid (9-cis RA) inhibited NO production by LPS
      stimulated microglia. Furthermore, a combination of 9-cis RA and the PPAR-alpha
      agonist fenofibrate cooperatively inhibited NO production by these cells. A
      combination of these agonists also selectively inhibited the expression of
      proinflammatory cytokines including IL-1beta, TNF-alpha, and IL-6 by LPS
      stimulated microglia. Collectively, these results raise the possibility that PPAR
      alpha and RXR agonists might have benefit as a therapy in MS, where activated
      microglia are believed to contribute to disease pathology.

PMID- 15968641
TI  - Ceramide regulation of the tumor suppressor phosphatase PTEN in rafts isolated
      from neurotumor cell lines.
AB  - The neutral sphingolipid ceramide has been implicated in the apoptotic death of
      cells by a number of different mechanisms, including activation of protein kinase
      B (Akt) phosphatase. Here we present evidence that ceramide recruits the tumor
      suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) into
      membrane microdomains (rafts), where it could act to reduce the levels of
      polyphosphoinositides necessary for the activation of Akt. A PTEN construct with
      a red-fluorescent protein (RFP) tag was overexpressed in both a human cell line
      derived from oligodendroglioma (HOG) and a rat pheochromocytoma cell line (PC12)
      by means of an inducible promoter system (Tet-Off). Induction of PTEN by removal
      of doxycycline enhanced both capsase-3 and cell death with staurosporine,
      wortmannin, or C2-ceramide, whereas antisense PTEN had the reverse effect.
      Overexpression of PTEN also increased acid sphingomyelinase (ASMase) activity.
      PTEN normally has a generalized (cytosolic/membrane) distribution, but treatment
      with C2-ceramide translocated a fraction of the PTEN to the plasma membrane,
      showing a plasma membrane distribution similar to that observed for a prenylated
      green-fluorescent (GFP) construct. PTEN was then shown to translocate to the
      detergent-resistant membrane microdomain fraction (raft) of the plasma membrane.
      The colocalization of sphingomyelinases, ceramide, polyphosphoinositides, and
      PTEN in the raft fraction further suggests that the association of these lipids
      is critical for regulating cell death.

PMID- 15968642
TI  - Rapid up-regulation of the neuronal serotoninergic phenotype by brain-derived
      neurotrophic factor and cyclic adenosine monophosphate: relations with raphe
      astrocytes.
AB  - Up-regulation of the neuronal serotoninergic phenotype in relation to astrocytic
      population was studied in primary cultures of rat embryonic rostral raphe. Short
      treatments (18 hr at day in vitro 4) with brain-derived neurotrophic factor
      (BDNF) or dibutyryl-cAMP (dBcAMP) increased the number of serotoninergic neurons
      by approximately 80% and approximately 40%, respectively, and markedly enhanced
      the branching (by 11-fold and 5-fold, respectively) and total length (by 4-fold
      and 2.5-fold, respectively) of their neurites. Concomitantly, under BDNF
      treatment, the astrocyte population was decreased by half and became mostly
      protoplasmic-like. In contrast, dBcAMP treatment also reduced the astrocytic cell
      density (by one-third) but induced a stellate morphology. Similar short treatment
      with the astrocyte-derived S100beta factor induced no modification of the
      serotonin (5-HT) neuronal phenotype nor of astrocytes morphology. Both BDNF- and
      cAMP-induced effects were abolished by simultaneous treatment with the specific
      tyrosine kinase inhibitor genistein, suggesting a role for the high-affinity BDNF
      receptor tyrosine kinase (TrkB). These data suggest that BDNF and cAMP, but not
      S100beta, rapidly induce both an up-regulation of the 5-HT neuronal phenotype and
      modifications of the neighboring astrocytes in a TrkB-dependent manner.

PMID- 15968643
TI  - Development and localisation of GABA(A) receptor alpha1, alpha2, beta2 and gamma2
      subunit mRNA in the chick optic tectum.
AB  - An in situ hybridisation technique was used to analyse the spatial and temporal
      pattern of expression of the mRNA encoding the four gamma-aminobutyric acid A
      (GABA(A)) receptor subunits (alpha1, alpha2, beta2, and gamma2) in the developing
      chick optic tectum. As a rule, layer i, layer h, and transient cell compartment 3
      (TCC3) show the highest levels of expression, especially of alpha1, alpha2 and
      beta2, which undergo striking changes as a function of time. Apart from these
      common features, the global pattern is highly complex and dynamic. Such
      complexity derives from the fact that each subunit exhibits a characteristically
      distinct pattern of expression and the temporal evolution of each differs in the
      different layers of the tectum. The influence of several developmental cell
      behaviours such as proliferation, neuronal migration, programmed cell death, and
      differentiation must be taken into account to understand pattern complexity and
      dynamics. Our results suggest that differences in the rate of subunit expression,
      particularly of alpha1, alpha2, and beta2, could have significant consequences on
      GABA(A) receptor complex subunit composition along development and on the
      functional properties of the GABA neurotransmitter system.

PMID- 15968644
TI  - Transplantation of embryonic spinal cord-derived neurospheres support growth of
      supraspinal projections and functional recovery after spinal cord injury in the
      neonatal rat.
AB  - Great interest exists in using cell replacement strategies to repair the damaged
      central nervous system. Previous studies have shown that grafting rat fetal
      spinal cord into neonate or adult animals after spinal cord injury leads to
      improved anatomic growth/plasticity and functional recovery. It is clear that
      fetal tissue transplants serve as a scaffold for host axon growth. In addition,
      embryonic Day 14 (E14) spinal cord tissue transplants are also a rich source of
      neural-restricted and glial-restricted progenitors. To evaluate the potential of
      E14 spinal cord progenitor cells, we used in vitro-expanded neurospheres derived
      from embryonic rat spinal cord and showed that these cells grafted into lesioned
      neonatal rat spinal cord can survive, migrate, and differentiate into neurons and
      oligodendrocytes, but rarely into astrocytes. Synapses and partially myelinated
      axons were detected within the transplant lesion area. Transplanted progenitor
      cells resulted in increased plasticity or regeneration of corticospinal and
      brainstem-spinal fibers as determined by anterograde and retrograde labeling.
      Furthermore, transplantation of these cells promoted functional recovery of
      locomotion and reflex responses. These data demonstrate that progenitor cells
      when transplanted into neonates can function in a similar capacity as transplants
      of solid fetal spinal cord tissue.

PMID- 15968645
TI  - Calpain activation in apoptosis of ventral spinal cord 4.1 (VSC4.1) motoneurons
      exposed to glutamate: calpain inhibition provides functional neuroprotection.
AB  - Glutamate toxicity has been implicated in cell death in neurodegenerative
      diseases and injuries. Glutamate-induced Ca2+ influx may mediate activation of
      calpain, a Ca2+-dependent cysteine protease, which in turn may degrade key
      cytoskeletal proteins. We investigated glutamate-mediated apoptosis of VSC4.1
      motoneurons and functional neuroprotection by calpain inhibition. Exposure of
      VSC4.1 cells to 10 microM glutamate for 24 hr caused significant increases in
      intracellular free [Ca2+], as determined by fura-2 assay. Pretreatment of cells
      with 10 or 25 microM calpeptin (a cell-permeable calpain-specific inhibitor) for
      1 hr prevented glutamate-induced Ca2+ influx. Western blot analyses showed an
      increase in Bax:Bcl-2 ratio, release of cytochrome c from mitochondria, and
      calpain and caspase-3 activities during apoptosis. Cell morphology, as evaluated
      by Wright staining, indicated predominantly apoptotic features following
      glutamate exposure. ApopTag assay further substantiated apoptotic features
      morphologically as well as biochemically. Our data showed that calpeptin mainly
      prevented calpain-mediated proteolysis and apoptosis and maintained whole-cell
      membrane potential, indicating functional neuroprotection. The results imply that
      calpeptin may serve as a therapeutic agent for preventing motoneuron
      degeneration, which occurs in amyotrophic lateral sclerosis and spinal cord
      injury. In this investigation, we also examined glutamate receptor subtypes
      involved in the initiation of apoptosis in VSC4.1 cells following exposure to
      glutamate. Our results indicated that the N-methyl-D-aspartate (NMDA) receptors
      contributed more than alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid
      (AMPA) receptors to glutamate-mediated Ca2+ influx and cell death mechanism.
      Inhibition of the activities of both NMDA and AMPA receptors protected VSC4.1
      cells from glutamate toxicity and preserved whole-cell membrane potential.

PMID- 15968646
TI  - Reduction of spinning sidebands in proton NMR of human prostate tissue with slow
      high-resolution magic angle spinning.
AB  - High-resolution magic angle spinning (HRMAS) NMR spectroscopy has proven useful
      for analyzing intact tissue and permitting correlations to be made between tissue
      metabolites and disease pathologies. Extending these studies to slow-spinning
      methodologies helps protect tissue pathological structures from HRMAS
      centrifuging damage and may permit the study of larger objects. Spinning
      sidebands (SSBs), which are produced by slow spinning, must be suppressed to
      prevent the complication of metabolic spectral regions. In this study human
      prostate tissues, as well as gel samples of a metabolite mixture solution, were
      measured with continuous-wave (CW) water presaturation on a 14.1T spectrometer,
      with HRMAS spinning rates of 250, 300, 350, 600, and 700 Hz, and 3.0 kHz. Editing
      the spectra by means of a simple minimum function (Min(A, B, ..., N) for N
      spectra acquired at different but close spinning rates) produced SSB-free
      spectra. Statistically significant linear correlations were observed for
      metabolite concentrations quantified from the Min(A, B, ..., N)-edited spectra
      generated at low spinning rates, with concentrations measured from the 3 kHz
      spectra, and also with quantitative pathology. These results indicate the
      empirical utility of this scheme for analyzing intact tissue, which also may be
      used as an adjunct tool in pathology for diagnosing disease.

PMID- 15968647
TI  - Artificial tumor model suitable for monitoring 31P and 13C NMR spectroscopic
      changes during chemotherapy-induced apoptosis in human glioma cells.
AB  - An artificial tumor method was developed to study cells inside the sensitive
      volume of an NMR spectrometer during growth and apoptosis. The tumor was composed
      of a 50:50 mixture of tightly packed porous-collagen and nonporous-polystyrene
      microspheres. The porous collagen served as a growth surface for the tumor cells,
      and the nonporous polystyrene served as a structural support to limit compression
      of the packed bed during perfusion. The microspheres were held between two porous
      polyethylene discs that were tightly sealed inside the NMR perfusion chamber. The
      new method was evaluated with two cell types: a mouse mammary tumor line
      (EMT6/SF) and a human glioma line (SF188). The results indicate that for both
      lines, approximately 10(9) metabolically active cells could be sustained for at
      least 1 week in the 12-cm(3) artificial tumor. Further, cells undergoing
      chemotherapy-induced apoptosis (which is known to cause detachment of cells from
      their surroundings) were retained in the artificial tumor. In preliminary 31P NMR
      studies, glioma cells treated with temozolomide (TMZ) exhibited reduced
      phosphocholine (PCh) levels relative to glycerophosphocholine (GPC) and
      diphosphodiester (DPDE) levels. They also exhibited sharply reduced oxygen
      consumption and TCA cycle 13C labeling, while they retained glycolytic activity.
      These metabolic changes are consistent with those that would be expected during
      mitochondrially-mediated apoptosis.

PMID- 15968648
TI  - Analysis and compensation of eddy currents in balanced SSFP.
AB  - Balanced steady-state free precession (SSFP) completely compensates for all
      gradients within each repetition time (TR), and is thus very sensitive to any
      magnetic field imperfection that disturbs the perfectly balanced acquisition
      scheme. It is demonstrated that balanced SSFP is especially sensitive to changing
      eddy currents that are induced by stepwise changing phase-encoding (PE)
      gradients. In contrast to the linear k-space trajectory, which has small
      variations between consecutive encoding steps, other encoding schemes (e.g.,
      centric, random, or segmented orderings) exhibit significant jumps in k-space
      between adjacent PE steps, and consequently induce rapidly changing eddy
      currents. The resulting disturbances induce significant image artifacts, such
      that compensation strategies are essential when nonlinear PE schemes are applied.
      Although direct annihilation of the induced eddy currents by additional, opposing
      magnetic fields has been investigated, it is limited by uncertainty regarding the
      time evolution of induced eddy currents. A generic (and thus system-unrelated)
      compensation strategy is proposed that consists of "pairing" of consecutive PE
      steps. Another approach is based on partial dephasing along the slice direction
      that annihilates eddy-current-induced signal oscillations. Both pairing of the PE
      steps and "through-slice equilibration" are easy to implement and allow the use
      of arbitrary k-space trajectories for balanced SSFP.

PMID- 15968650
TI  - Eight-channel phased array coil and detunable TEM volume coil for 7 T brain
      imaging.
AB  - An eight-channel receive-only brain coil and table-top detunable volume transmit
      coil were developed and tested at 7 T for human imaging. Optimization of this
      device required attention to sources of interaction between the array elements,
      between the transmit and receive coils and minimization of common mode currents
      on the coaxial cables. Circular receive coils (85 mm dia.) were designed on a
      flexible former to fit tightly around the head and within a 270-mm diameter TEM
      transmit volume coil. In the near cortex, the array provided a fivefold increase
      in SNR compared to a TEM transmit-receive coil, a gain larger than that seen in
      comparable coils at 3 T. The higher SNR gain is likely due to strong dielectric
      effects, which cause the volume coil to perform poorly in the cortex compared to
      centrally. The sensitivity and coverage of the array is demonstrated with high
      resolution images of the brain cortex.

PMID- 15968649
TI  - Variable field of view for spatial resolution improvement in continuously moving
      table magnetic resonance imaging.
AB  - An approach is described in which the field of view (FOV) along the Y
      (right/left) phase encoding direction can be dynamically altered during a
      continuously moving table (CMT) coronal acquisition for extended FOV MRI. We
      hypothesize that with this method, regions of the anatomy exhibiting
      significantly different lateral widths can be imaged with a matching local
      FOV(Y), thereby improving local lateral spatial resolution. k-space raw data from
      the variable-FOV CMT acquisition do not allow simple Fourier reconstruction due
      to the presence of a mixture of phase encodes sampled at different Deltak(Y)
      intervals. In this work, we employ spline interpolation to reregister the mixed
      data set onto a uniformly sampled k-space grid. Using this interpolation scheme,
      we present phantom and peripheral contrast-enhanced MR angiography results
      demonstrating an approximate 45% improvement in local lateral spatial resolution
      for continuously moving table acquisitions.

PMID- 15968651
TI  - Quantitative T(1rho) and adiabatic Carr-Purcell T2 magnetic resonance imaging of
      human occipital lobe at 4 T.
AB  - The feasibility of performing quantitative T(1rho) MRI in human brain at 4 T is
      shown. T(1rho) values obtained from five volunteers were compared with T2 and
      adiabatic Carr-Purcell (CP) T2 values. Measured relaxation time constants
      increased in order from T2, CP-T2, T(1rho) both in white and gray matter,
      demonstrating differential sensitivities of these methods to dipolar interactions
      and/or proton exchange and diffusion in local microscopic field gradients, which
      are so-called dynamic averaging (DA) processes. In occipital lobe, all relaxation
      time constants were found to be higher in white matter than in gray matter,
      demonstrating contrast denoted as an "inverse transverse relaxation contrast."
      This contrast persisted despite changing the delay between refocusing pulses or
      changing the magnitude of the spin-lock field strength, which suggests that it
      does not originate from DA, as might be induced by the presence of Fe, but rather
      is related to dipolar interactions in the brain tissue.

PMID- 15968652
TI  - Liver iron concentration evaluated by two magnetic methods: magnetic resonance
      imaging and magnetic susceptometry.
AB  - Quantification of liver iron concentration (LIC) is crucial in the management of
      patients suffering from certain pathologies that can produce iron overload, such
      as Cooley's anemia and hemochromatosis. All of these patients must control the
      level of iron deposits in their organs to avoid the toxicity of high LIC, which
      is potentially lethal. This paper describes experimental protocols for LIC
      measurement using two magnetic techniques: magnetic resonance imaging (MRI) and
      biomagnetic liver susceptometry (BLS). MRI proton transverse relaxation rate (R2)
      and image intensity, evaluated pixel by pixel, were used as indicators of iron
      load in the tissue. LIC measurement by BLS was performed using an AC
      superconducting susceptometer system. A group of 23 patients with a large range
      of iron overload (0.9 to 34.5 mgFe/g(dry tissue)) was evaluated with both
      techniques (MRI x BLS). A significant linear correlation (r = 0.89-0.95) was
      found between the LIC by MRI and by BLS. These results show the feasibility of
      using two noninvasive methodologies to evaluate liver iron store in a large
      concentration range. Both methodologies represent an equivalent precision.

PMID- 15968653
TI  - Lipid content in the musculature of the lower leg: evaluation with high
      resolution spectroscopic imaging.
AB  - A novel spectroscopic imaging method with high spectral and spatial resolution
      was developed for the specific goal of assessing muscle fat. Sensitivity to the
      methylene and methyl protons of fatty acids was improved by the use of a binomial
      1 1 excitation pulse instead of the standard radiofrequency (RF) pulse.
      Acceptable measurement time is achieved by using a narrow spectral bandwidth (6
      ppm). The spectral resolution is sufficient to resolve extramyocellular (EMCL)
      and intramyocellular (IMCL) lipids. A post-detection data processing scheme that
      permits correction of spectral artifacts caused by chemical shifts, spectral line
      aliasing, and magnetic field inhomogeneities is suggested. The lipid content in
      different lower leg muscles was evaluated. Muscle fiber orientation was taken
      into account in assessing quantities of EMCL and IMCL. The proposed technique
      allows small amounts of inhomogeneously distributed muscle lipids to be
      quantified.

PMID- 15968654
TI  - PSF-choice: a novel MRI method for shaping point-spread functions in phase
      encoding dimensions.
AB  - An imaging method to obtain arbitrary point-spread functions (PSFs) in phase
      encoding dimensions is described. This method, called PSF-Choice, is particularly
      relevant for applications, such as spectroscopic imaging, in which only a very
      few phase encodes are acquired and ringing artifact can be a serious problem. PSF
      Choice uses partial 2D RF excitations to produce aliased excitations that are
      encoded using standard phase-encoding gradients. Theoretically, the PSF of the
      reconstructed result depends only on the RF excitation profile. Simulations
      demonstrate that a Gaussian-like PSF can be achieved, eliminating the side lobes
      that are associated with ringing artifact. It is further shown that neither the
      spatial resolution (as represented by the width of the PSF) nor the signal-to
      noise ratio (SNR) of the method is adversely affected when compared to standard
      phase encoding. In the sense that the same number of encodes are required as with
      standard phase encoding, temporal resolution is also maintained. Phantom
      experiments demonstrate the initial feasibility of the method to eliminate
      ringing artifact.

PMID- 15968655
TI  - Transmission line for improved RF safety of interventional devices.
AB  - A new concept is proposed to improve the safety of transmission lines with
      respect to heating during RF transmission. It is based on the integration of
      transformers into the transmission line. The concept was applied to an active
      tracking device. Miniature transformers were designed, and two types of tracking
      devices were built based on a standard line and a transformer line. Temperature
      measurements were performed for both devices during high specific absorption rate
      (SAR) scanning, and the suppression of RF heating to a physiologically non
      relevant level was demonstrated for the transformer device. The transmission
      properties of the transformer line were examined in simulations and RF
      measurements. Active tracking with the transformer device performed robustly in
      the phantom. Because of the favorable signal transmission properties of the
      tested device, it is expected that the concept can be applied to the construction
      of clinical devices for tracking and intravascular imaging, which are RF-safe
      under clinical SAR conditions. Since the transformer line has a large bandwidth,
      the concept may also be applied for RF-safe transmission of non-MR signals.

PMID- 15968656
TI  - Method of generalized projections algorithm for image-based reduction of
      artifacts in radial imaging.
AB  - This work describes the method of generalized projections (MGP) as an image
      based, postprocessing method to correct for phase inconsistencies caused by echo
      misalignments in radial imaging. Computer simulations show that MGP can correct
      for echo shifts, constant phase, and amplitude errors, but the accuracy of the
      correction is limited, and this accuracy is reduced by the addition of more
      degrees of freedom. In phantom experiments, MGP performed better than magnitude
      filtered backprojection and anti-parallel projections correction.

PMID- 15968657
TI  - Nonnvasive assessment of vascular architecture and function during modulated
      blood oxygenation using susceptibility weighted magnetic resonance imaging.
AB  - Susceptibility weighted imaging (SWI) is a BOLD-sensitive method for visualizing
      anatomical features such as small cerebral veins in high detail. The purpose of
      this study was to evaluate high-resolution SWI in combination with a modulation
      of blood oxygenation by breathing of air, carbogen, and oxygen and to directly
      visualize the effects of changing blood oxygenation on the magnetic field inside
      and around venous blood vessels. Signal changes associated with the response to
      carbogen and oxygen breathing were evaluated in different anatomic regions in
      healthy volunteers and in two patients with brain tumors. In the magnitude images
      inhalation of carbogen led to significant signal intensity changes ranging from
      +4.4 +/- 1.9% to +9.5 +/- 1.4% in gray matter and no significant changes in
      thalamus, putamen, and white matter. During oxygen breathing mean signal changes
      were smaller than during carbogen breathing. The method is capable of producing
      high-resolution functional maps of BOLD response to carbogen and oxygen breathing
      as well as high-resolution images of venous vasculature. Its sensitivity to
      changes in blood oxygenation was demonstrated by in vivo visualization of the
      BOLD effect via phase imaging.

PMID- 15968658
TI  - Effect of experimental parameters on high b-value q-space MR images of excised
      rat spinal cord.
AB  - The influence of diffusion time (delta), gradient duration (delta), and TE on the
      appearance of high b-value q-space diffusion MR images of excised rat spinal cord
      (SC) was evaluated. The water signal decays in the white (WM) and gray matter
      (GM) were analyzed when the diffusion was measured perpendicular ( perpendicular)
      and parallel to the fibers of the SC, using three different approaches: single
      component q-space analysis, the biexponential model, and the bi-Gaussian fit of
      the displacement distribution profile. Probability and displacement contrast and
      anisotropy indices were calculated for the WM and GM. It was found that WM/GM
      contrast increases as the diffusion time is increased when diffusion is measured
      perpendicular to the long axis of the SC. At a diffusion time of 50 ms, when
      diffusion was measured parallel to the fibers of the SC, the displacement was
      found to be higher for GM as compared to WM. For this direction the WM/GM
      contrast increased when diffusion time was increased, although here the changes
      were much less pronounced than for the perpendicular direction. The WM/GM
      displacement contrast nearly disappears for a diffusion time of 150 ms, when
      diffusion is measured parallel to the fibers of the SC. As expected, the
      anisotropy indices were found to be higher in WM than in GM, and increased with
      the increase in diffusion time. Both delta and TE affected the extracted
      parameters. It was found that long delta and long TE overemphasizes the apparent
      slow-diffusing water component of the SC, which is also the more restricted one.
      It is demonstrated that the single-component q-space analysis best describes
      diffusion in WM when diffusion is measured perpendicular to the fibers of the SC.
      In other cases, a more complete description is obtained by using two-component
      models.

PMID- 15968659
TI  - Miniature self-contained intravascular magnetic resonance (IVMI) probe for
      clinical applications.
AB  - A miniature (1.73 mm in diameter) NMR probe, which contains a magnet and a
      radiofrequency (RF) coil, is presented. This probe is integrated at the tip of a
      standard catheter and can be inserted into the human coronary arteries, creating
      local magnetic fields needed to obtain the NMR signal from the blood vessel
      walls, without the need for external magnet or RF coils. The basic theory
      governing the probe performance in terms of signal-to-noise-ratio and contrast
      parameters is presented, along with measured results from test samples. The NMR
      signal can be analyzed to obtain tissue contrast parameters such as T1, T2 and
      the diffusion coefficient, which may be used to detect lipid-rich vulnerable
      plaques in the coronary arteries.

PMID- 15968660
TI  - Measurement of cerebrospinal fluid oxygen partial pressure in humans using MRI.
AB  - Fluid-attenuated inversion recovery (FLAIR) images obtained during the
      administration of supplemental oxygen demonstrate a hyperintense signal within
      the cerebrospinal fluid (CSF) that is likely caused by T1 changes induced by
      paramagnetic molecular oxygen. Previous studies demonstrated a linear
      relationship between the longitudinal relaxation rate (R1 = 1/T1) and oxygen
      content, which permits quantification of the CSF oxygen partial pressure
      (P(csf)O2). In the current study, CSF T1 was measured at 1.5 T in the lateral
      ventricles, third ventricle, cortical sulci, and basilar cisterns of eight normal
      subjects breathing room air or 100% oxygen. Phantom studies performed with
      artificial CSF enabled absolute P(csf)O2 quantitation. Regional P(csf)O2
      differences on room air were observed, from 65 +/- 27 mmHg in the basilar
      cisterns to 130 +/- 49 mmHg in the third ventricle. During 100% oxygen, P(csf)O2
      increases of 155 +/- 45 and 124 +/- 34 mmHg were measured in the basilar cisterns
      and cortical sulci, respectively, with no change observed in the lateral or third
      ventricles. P(csf)O2 measurements in humans breathing room air or 100% oxygen
      using a T1 method are comparable to results from invasive human and animal
      studies. Similar approaches could be applied to noninvasively monitor oxygenation
      in many acellular, low-protein body fluids.

PMID- 15968661
TI  - Correction of MR image distortions induced by metallic objects using a 3D cubic B
      spline basis set: application to stereotactic surgical planning.
AB  - Metallic implants in MRI cause spin-echo (SE) images to be distorted in the slice
      and frequency-encoding directions. Chang and Fitzpatrick (IEEE Trans Med Imaging
      1992;11:319-329) proposed a distortion correction method (termed the CF method)
      based on the magnitude images from two SE acquisitions that differ only in the
      polarity of the frequency-encoding and slice-selection gradients. In the present
      study we solved some problems with the CF method, primarily by modeling the field
      inhomogeneities as a single 3D displacement field built by 3D cubic B-splines.
      The 3D displacement field was applied in the actual distortion direction in the
      slice/frequency-encoding plane. To account for patient head motion, a 3D rigid
      body motion correction was also incorporated in the model. Experiments on a
      phantom containing an aneurysm clip showed that the knot spacing between the B
      splines is a very important factor in both the final image quality and the
      processing speed. Depending on the knot spacing and the image volume size, the
      number of unknowns range from a few thousands to over 100,000, leading to
      processing times ranging from minutes to days. Optimal knot spacing, a means of
      increasing the processing speed, and other parameters are investigated and
      discussed.

PMID- 15968662
TI  - Influence of proton T1 on oxymetry using Overhauser enhanced magnetic resonance
      imaging.
AB  - In Overhauser enhanced magnetic resonance imaging (OMRI) for in vivo measurement
      of oxygen partial pressure (pO2), a paramagnetic contrast agent is introduced to
      enhance the proton signal through dynamic nuclear polarization. A uniform proton
      T1 is generally assumed for the entire region of interest for the computation of
      pO2 using OMRI. It is demonstrated here, by both phantom and in vivo (mice)
      imaging, that such an assumption may cause erroneous estimate of pO2. A direct
      estimate of pixel-wise T1 is hampered by the poor native MR intensities, owing to
      the very low Zeeman field (15-20 mT) in OMRI. To circumvent this problem, a
      simple method for the pixel-wise mapping of proton T1 using the OMRI scanner is
      described. A proton T1 image of a slice through the center of an SCC tumor in a
      mouse clearly shows a range of T1 distribution (0.2 approximately 1.6 s).
      Computation of pO2 images using pixel-wise T1 values promises oximetry with
      minimal artifacts by OMRI.

PMID- 15968663
TI  - Metal artifacts caused by gradient switching.
AB  - In metal parts, e.g., implants or instruments, eddy currents can be induced from
      gradient switching if positioned off-center inside the MR scanner. For the first
      time, a systematic analysis of related artifacts was performed. Current strength
      increases in conjunction with increasing size of the part, increasing electrical
      conductivity, distance from isocenter, and increasing gradient strengths. A xy
      plane oriented copper ring (d(o) = 20 mm, d(i) = 15 mm, 2 mm thick) was examined
      at isocenter and at x = 15 cm, y = z = 0. Comparisons of xy-, xz-, and yz-slices,
      recorded for both possibilities to select encoding directions, revealed effects
      from ramp-down of the slice-selection and ramp-up of the read-out gradient. Near
      the metal part, temporary inhomogeneities were superimposed to the static field
      and spin-dephasing signal loss resulted, despite using spin-echo technique.
      Artifacts depended on excitation and read-out bandwidth. For an equivalent
      titanium ring, conductivity related effects could not be ascertained but distinct
      susceptibility effects occurred. MR compatibility of implants/instruments
      therefore requires both low susceptibility and low conductivity.

PMID- 15968665
TI  - Fast high-resolution T1 mapping of the human brain.
AB  - A sequence for the acquisition of high-resolution T1 maps, based on magnetization
      prepared multislice fast low-angle shot (FLASH) imaging, is presented. In
      contrast to similar methods, no saturation pulses are used, resulting in an
      increased dynamic range of the relaxation process. Furthermore, it is possible to
      acquire data during all relaxation delays because only slice-selective
      radiofrequency (RF) pulses are used for inversion and excitation. This allows for
      a reduction of the total acquisition time, or scanning with a reduced bandwidth,
      which improves the signal-to-noise ratio (SNR). The method generates quantitative
      T1 maps with an in-plane resolution of 1 mm, slice thickness of 4 mm, and whole
      brain coverage in a clinically acceptable imaging time of about 19 s per slice.
      It is shown that the use of off-center RF pulses does not result in imperfect
      inversion or magnetization transfer (MT) effects. In addition, an improved
      fitting algorithm based on smoothed flip angle maps is presented and tested
      successfully.

PMID- 15968666
TI  - New method for the simultaneous detection of metabolites and water in localized
      in vivo 1H nuclear magnetic resonance spectroscopy.
AB  - A new two-scan method for localized 1H in vivo NMR spectroscopy (MRS) without
      water suppression (WS) is described. In one of the scans, two chemical shift
      selective 180 degrees pulses are applied prior to a standard localization
      sequence to invert all metabolite signals upfield and downfield from water, which
      remains unaffected. The difference spectrum records the metabolites whereas water
      and accompanying gradient induced artifacts are widely suppressed. The method was
      implemented on a 4.7-T system using point resolved spectroscopy with a short echo
      time of 18 ms. Phantom measurements proved the feasibility of absolute
      quantification using water as an internal reference. Measurements on healthy rat
      brain yielded comparable spectrum quality as measurements with water
      presaturation. The method does not require additional adjustments or
      sophisticated data postprocessing and scales favorably with increasing B(0)
      field. Therefore, the method should be useful for 1H MRS without WS. Although the
      two-step method doubles the minimum total measurement time, it may also be of
      interest for spectroscopic imaging (SI) without WS, in particular if fast SI
      techniques are applied.

PMID- 15968667
TI  - Manganese enhanced magnetic resonance imaging of normal and ischemic canine
      heart.
AB  - The ability of MnCl2 to enhance canine myocardium and to delineate ischemic areas
      is demonstrated. A dose-response curve was measured using T1 weighted images in
      11 dogs. MnCl2 (36, 113, 360, and 3600 micromol) was infused over a period of 3
      min. Signal intensity increased linearly with MnCl2 dose. At 113 micromol (
      approximately 10 micromol/kg) the steady-state increase in intensity averaged 212
      +/- 34%. No significant physiologic effects due to the infused MnCl2 were
      detected except at the highest dose where there was a cardiac depressive effect.
      Ischemia was induced by occluding the left anterior descending coronary artery in
      5 dogs. At an infused dose of 113 micromol, MnCl2 clearly demarcated the ischemic
      zone during coronary occlusion. Contrast enhancement in the ischemic zone was
      less than 30% compared with normal tissue (P < 0.03). In conclusion, the
      intracellular contrast agent MnCl2 enhances the canine heart and shows promise in
      detecting ischemia at doses that do not cause adverse cardiac effects.

PMID- 15968668
TI  - Optimization of 3D contrast-enhanced pulmonary magnetic resonance angiography in
      pediatric patients with congenital heart disease.
AB  - Contrast kinetics were studied in the main pulmonary artery (MPA) and ascending
      aorta (AAo) of 12 children with congenital heart disease. This information was
      used to optimize the timing of data acquisition for contrast-enhanced MR
      angiography in these vessels. To reduce contrast-agent dosage in these fragile
      patients, contrast enhancement was measured during routine diagnostic 3D magnetic
      resonance (MR) angiography instead of using test-bolus methods. This was possible
      by acquiring 2D cross-sectional images of the MPA and AAo during the 3D scan.
      Time-to-peak in the MPA and AAo was 4.9 +/- 2.2 and 6.1 +/- 2.2 s, respectively,
      while the transit time between the two vessels was 4.5 +/- 0.6 s. A point-spread
      function analysis showed that intravascular signal strength was maximized if data
      acquisition began 4.7 +/- 2.3 s after the first arrival of contrast in the MPA
      and 5.6 +/- 2.3 s in the AAo. Little signal loss and artifact resulted when
      longer acquisition delays were used because contrast-agent clearance was slow.
      Based on these results, MR angiography of both the MPA and the AAo in children
      with congenital heart disease can be performed using elliptic-centric k-space
      sampling and a trigger delay of 7.9 s after contrast arrival in the AAo (i.e.,
      time-to-peak signal strength in the AAo plus one SD to account for intersubject
      variability).

PMID- 15968669
TI  - Suppression of lipid artifacts in amide proton transfer imaging.
AB  - Amide proton transfer (APT) imaging is a type of chemical exchange saturation
      transfer imaging in which the amide protons of cellular proteins and peptides are
      saturated and detected via the water resonance. To study this effect,
      conventional magnetization transfer and direct saturation effects in the
      frequency-dependent water saturation spectrum (z-spectrum) need to be removed by
      asymmetry analysis with respect to the water frequency offset. When using echo
      planar imaging, it was found that unequal pericranial fat saturation at
      equidistant higher and lower frequencies with respect to water leads to a lipid
      artifact in APT asymmetry images. It is demonstrated that a chemical-shift
      selective refocusing pulse in combination with crusher gradients can suppress
      this artifact and provide high-quality images.

PMID- 15968670
TI  - Evolution of the longitudinal magnetization for pulse sequences using a fast spin
      echo readout: application to fluid-attenuated inversion-recovery and double
      inversion-recovery sequences.
AB  - The fast spin-echo (FSE) sequence is frequently used as a fast data-readout
      technique in conjunction with other pulse sequence elements, such as in fluid
      attenuated inversion-recovery (FLAIR) and double inversion-recovery (DIR)
      sequences. In order to implement those pulse sequences, an understanding is
      required of how the longitudinal magnetization evolves during the FSE part of the
      sequence. This evolution has been addressed to a certain extent by previous
      publications, but the DIR literature in particular appears to be replete with
      approximations to the exact expression for the longitudinal magnetization, and
      several papers contain errors. Equations are therefore presented here for the
      evolution of the longitudinal magnetization for a FSE readout. These are then
      applied to calculate the magnetization available immediately prior to the 90
      degrees imaging pulse for the FLAIR-FSE and DIR-FSE pulse sequences.

PMID- 15968671
TI  - Inherently self-calibrating non-Cartesian parallel imaging.
AB  - The use of self-calibrating techniques in parallel magnetic resonance imaging
      eliminates the need for coil sensitivity calibration scans and avoids potential
      mismatches between calibration scans and subsequent accelerated acquisitions
      (e.g., as a result of patient motion). Most examples of self-calibrating
      Cartesian parallel imaging techniques have required the use of modified k-space
      trajectories that are densely sampled at the center and more sparsely sampled in
      the periphery. However, spiral and radial trajectories offer inherent self
      calibrating characteristics because of their densely sampled center. At no
      additional cost in acquisition time and with no modification in scanning
      protocols, in vivo coil sensitivity maps may be extracted from the densely
      sampled central region of k-space. This work demonstrates the feasibility of self
      calibrated spiral and radial parallel imaging using a previously described
      iterative non-Cartesian sensitivity encoding algorithm.

PMID- 15968672
TI  - Parallel imaging for NMR microscopy at 14.1 Tesla.
AB  - Parallel imaging techniques using arrays of mutually decoupled coils have become
      standard on almost all clinical imaging systems. Such techniques also have great
      potential for high-field magnetic resonance (MR) microscopy, where measurement
      times are usually long and susceptibility artifacts can be severe. However, it is
      technically very challenging to design efficient high-frequency phased arrays for
      small-diameter, vertical-bore magnets, especially since standard decoupling
      methods, such as impedance mismatched preamplifiers, cannot be easily integrated.
      A four-coil phased array was constructed for microimaging at 600 MHz, and
      sensitivity encoding (SENSE) and generalized autocalibrating partially parallel
      acquisitions (GRAPPA) reconstructions of spin-echo and echo-planar images of the
      mouse brain were performed to reduce imaging time and susceptibility artifacts,
      respectively.

PMID- 15968673
TI  - Optimizing PRESS localized citrate detection at 3 Tesla.
AB  - Analytical methods are used to characterize the response of the strongly coupled
      two-spin system of citrate to point-resolved spectroscopy (PRESS)-based sequences
      at 3 T. The signal output is analyzed line by line, as well as in the Cartesian
      product operator basis. Patterns with a periodicity of 80.9 ms are identified.
      Furthermore, it is shown that at TE = n . 80.9 ms (n in {0,1,2,...}), the spin
      evolution can be described without direct reference to strong coupling terms. The
      theoretical results are found to be in good agreement with in vivo experiments.
      These results can be used to design protocols for prostate MRS and MRSI at 3 T,
      and give guidelines for optimizing spin-echo-based acquisition schemes for
      detecting two-spin systems at arbitrary field strengths.

PMID- 15968674
TI  - In-plane velocity encoding with coherent steady-state imaging.
AB  - Standard phase-contrast flow quantification (PC-FQ) using radiofrequency (RF)
      spoiled steady-state (SS) incoherent gradient-echo sequences have a relatively
      low signal-to-noise ratio (SNR). Unspoiled SS coherent (SSC) gradient-echo
      sequences have a higher intrinsic SNR and are T2/T1 weighted so that blood has a
      relatively large signal compared to other tissues. An SSC sequence that was
      modified to allow in-plane velocity encoding is presented. Velocity encoding was
      achieved by inverting the readout gradients. This offers the benefit that there
      is no resultant increase in repetition time (TR), which avoids increased
      sensitivity to off-resonance artifacts when conventional velocity-encoding
      methods using separate velocity-encoding gradients are extended to SSC sequences.
      The results of standard PC-FQ and the new method from in vitro experiments of
      constant and sinusoidal flow, and in vivo imaging of the carotid artery were
      compared. Vector field maps and paths obtained from particle-tracking
      calculations based on the velocity-encoded images were used to visualize the
      velocity data. The technique has the potential to increase the precision of PC-FQ
      measurements.

PMID- 15968675
TI  - Generic method for imaging transgene expression.
AB  - We propose a generic method to report on gene expression based on the use of an
      antigen-antibody reporting system and visualization by MRI. This methodology was
      demonstrated using a truncated form of the H2K(k) antigen, tH2K(k), as the
      nonendogenous antigen to be imaged. HeLa cells, transfected to express tH2K(k),
      exposed to tH2K(k) antibodies conjugated to a superparamagnetic iron oxide
      particle, generated strong negative contrast compared to non-H2K(k) expressing
      cells by MRI. T(2) of the tH2K(k) expressing cells was 57.6 +/- 17.0 ms, compared
      to 424.0 +/- 38.7 and 445.4 +/- 47.2 ms for the mock transfected and
      nontransfected cells, respectively (P < 0.001). tH2K(k) expression in the former
      cells was confirmed by flow cytometry, fluorescence, and electron microscopy. The
      methodology can be adapted to image in vivo other nonendogenous antigens in
      cells/tissues.

PMID- 15968676
TI  - Magnetization transfer weighted imaging in the upper cervical spinal cord using
      cerebrospinal fluid as intersubject normalization reference (MTCSF imaging).
AB  - The magnetization transfer ratio (MTR) is a reliable measure of MT effects
      because it employs an internal standard that allows quantitative comparison
      between subjects, independent of other contrasts, coil loading, and coil
      sensitivity profiles. However, at very high spatial resolution in the spinal cord
      at 1.5 T, the use of MTR quantification has been hampered by low signal-to-noise
      ratio (SNR) and acute sensitivity to motion. Here, the suitability of
      cerebrospinal fluid (CSF) as an alternative inter-subject MT signal intensity
      reference for the spine is evaluated. Contrary to MTR, this so-called MTCSF
      internal standard does not remove interfering T(1), T(2), and spin density
      contrast and is not expected to be able to discriminate between myelination and
      inflammation effects. However, it can detect initial changes in myelination when
      signal alterations are not yet detectable by conventional MRI. As a first
      example, this is demonstrated for the noninflammatory spinal cord white matter
      disease adrenomyeloneuropathy.

PMID- 15968677
TI  - Magnetic susceptibility matching at the air-tissue interface in rat lung by using
      a superparamagnetic intravascular contrast agent: influence on transverse
      relaxation time of hyperpolarized helium-3.
AB  - Transverse relaxation of hyperpolarized helium-3 magnetization in respiratory
      airways highly depends on local magnetic field gradients induced by the magnetic
      susceptibility difference between gas and pulmonary tissue. Fast transverse
      relaxation is known to be an important feature that yields information about lung
      microstructure and function, but it is also an essential limitation in designing
      efficient strategies for lung imaging. Using intravascular injections of a
      superparamagnetic contrast agent in rats, it was possible to increase the overall
      susceptibility of the perfused lung tissues and hence to match it with the gas
      susceptibility. The transverse decay time constant of inhaled hyperpolarized
      helium-3 was measured in multiple-spin-echo experiments at 1.5 T as a function of
      the superparamagnetic contrast agent concentration in the animal blood. The time
      constant was increased by a factor of 3 when an optimal concentration was reached
      as predicted for susceptibility matching by combining intrinsic susceptibilities
      of tissue, blood, and gas.

PMID- 15968678
TI  - 1H MRS-visible lipids accumulate during apoptosis of lymphoma cells in vitro and
      in vivo.
AB  - Proton MRS detection of cellular lipid accumulation has been suggested as a
      noninvasive method for detecting apoptosis or programmed cell death (PCD) in
      vivo. The spectral changes that have been observed in apoptotic cells include a
      general increase in lipid signals and a specific increase in the ratio of the
      lipid methylene-to-methyl peak intensities. These changes were investigated here
      following drug-induced apoptosis, both in vitro with a murine lymphoma cell line
      (EL-4) and in vivo following implantation of these cells to form subcutaneous
      tumors. Fluorescence microscopy and flow cytometric measurements with a
      lipophilic dye revealed an accumulation of cytoplasmic lipid droplets in isolated
      EL-4 cells undergoing etoposide-induced apoptosis. (1)H MR spectra (both
      diffusion-weighted (DW) and unweighted) showed an increase in lipid signals.
      However, the methylene/methyl peak ratio showed only minimal changes. Localized
      in vivo spectroscopy of EL-4 tumors also showed an increase in lipid signals,
      including a signal from polyunsaturated lipid at 2.8 ppm, after 16-24 h of drug
      treatment. Again there was no significant change in the methylene/methyl peak
      ratio. This study confirms that MRS-detectable lipids accumulate in tumor cells
      undergoing apoptosis, and therefore may be usable as a marker for the noninvasive
      detection of tumor cell apoptosis in the clinic.

PMID- 15968679
TI  - MRI detection of macrophage activity after experimental stroke in rats: new
      indicators for late appearance of vascular degradation?
AB  - Focal cerebral ischemia was induced in rats and followed with high-resolution MRI
      methods for a chronic period of 10 weeks. Two weeks after stroke induction and at
      the end of the observation period, conventional histological analysis was
      combined with immunohistochemical staining for macrophages and with Prussian blue
      staining for the detection of ferric iron. In the late chronic phase, a patchy
      hypointensity was observed in the ischemic caudoputamen exclusively on T2*
      weighted (T2*W) images, with no change in quantitative T(1) and T(2) relaxation
      time maps. This characteristic MRI pattern is different from hemorrhagic
      transformations (HTs) at earlier time points (2 weeks post stroke induction),
      which became apparent on images of all three imaging sequences. The exclusive T2*
      sensitive hypointensity colocalized with iron-positive macrophages in the lesion
      territory at this time. These iron-containing macrophages were found
      predominantly around blood vessels in the ischemic tissue, and interpreted as the
      result of a phagocytotic incorporation of red blood cells leaking from slowly
      degrading vessels. The present investigation demonstrates the sensitivity of
      heavily T2*W 3D MRI for observing the inflammatory response in the chronic phase
      after stroke, without prior systemic labeling of the blood-borne macrophages by
      iron oxide nanoparticles.

PMID- 15968681
TI  - Simultaneous radiofrequency (RF) heating and magnetic resonance (MR) thermal
      mapping using an intravascular MR imaging/RF heating system.
AB  - Previous studies have confirmed the possibility of using an intravascular MR
      imaging guidewire (MRIG) as a heating source to enhance vascular gene
      transfection/expression. This motivated us to develop a new intravascular system
      that can perform MR imaging, radiofrequncy (RF) heating, and MR temperature
      monitoring simultaneously in an MR scanner. To validate this concept, a series of
      mathematical simulations of RF power loss along a 0.032-inch MRIG and RF energy
      spatial distribution were performed to determine the optimum RF heating
      frequency. Then, an RF generator/amplifier and a filter box were built. The
      possibility for simultaneous RF heating and MR thermal mapping of the system was
      confirmed in vitro using a phantom, and the obtained thermal mapping profile was
      compared with the simulated RF power distribution. Subsequently, the feasibility
      of simultaneous RF heating and temperature monitoring was successfully validated
      in vivo in the aorta of living rabbits. This MR imaging/RF heating system offers
      a potential tool for intravascular MR-mediated, RF-enhanced vascular gene
      therapy.

PMID- 15968680
TI  - Uncovering of intracellular water in cultured cells.
AB  - The complexity of biologic tissues, with multiple compartments each with its own
      diffusion and relaxation properties, requires complex formalisms to model water
      signal in most magnetic resonance imaging or magnetic resonance spectroscopy
      experiments. In this article, we describe a magnetic susceptibility-induced shift
      in the resonance frequency of extracellular water by the introduction of a
      gadolinium contrast agent to medium perfusing a hollow fiber bioreactor. The
      frequency shift of the extracellular water (+185 Hz at 9.4 T) uncovers the
      intracellular water and allows direct measurement of motional and relaxation
      properties of the intracellular space. The proposed method provides a unique tool
      for understanding the mechanisms underlining diffusion and relaxation in the
      intracellular space.

PMID- 15968682
TI  - A rapid microarray based whole genome analysis for detection of uniparental
      disomy.
AB  - To date, uniparental disomy (UPD) with phenotypic relevance is described for
      different chromosomes and it is likely that additional as yet unidentified UPD
      phenotypes exist. Due to technical difficulties and limitations of time and
      resources, molecular analyses for UPD using microsatellite markers are only
      performed in cases with specific phenotypic features. In this study, we carried
      out a whole genome UPD screening based on a microarray genotyping technique. Six
      patients with the diagnosis of both complete or segmental UPD including Prader
      Willi syndrome (PWS; matUPD15), Angelman syndrome (AS; patUPD15), Silver-Russell
      syndrome (SRS; matUPD7), Beckwith-Wiedemann syndrome (BWS; patUPD11p),
      pseudohypoparathyroidism (PHP; patUPD20q) and a rare chromosomal rearrangement
      (patUPD2p, matUPD2q), were genotyped using the GeneChip Human Mapping 10K Array.
      Our results demonstrate the presence of UPD in the patients with high efficiency
      and reveal clues about the mechanisms of UPD formation. We thus conclude that
      array based SNP genotyping is a fast, cost-effective, and reliable approach for
      whole genome UPD screening.

PMID- 15968683
TI  - Consideration of the neural crest and its skeletal derivatives in the context of
      novelty/innovation.
AB  - I examine the neural crest and skeletal tissues derived from neural crest cells
      in the context of novelty/innovation by asking whether the neural crest is a
      novel tissue and whether the evolutionary origin of the neural crest required
      innovative developmental processes. As a vertebrate autapomorphy, the neural
      crest is a novel structure. I equate novelty with innovation and take a
      hierarchical approach. Some other workers separate the two, using novelty for new
      structures not found in an ancestor and not homologous with a feature in an
      ancestor, and innovation for the new processes required to generate the novel
      structure. While development clearly evolves, I do not separate those processes
      that result in the production of novel features from those that lead to change in
      existing structures, whether that change is a transition or transformation from
      one homologous feature to another (fins-->tetrapod limbs or locomotory appendages
      ->crustacean maxilliped feeding appendages). The existence of novelties causes us
      to consider the concept of latent homology. Neural crest cells form cartilage,
      dentine and bone. Cartilage is found in invertebrates and so is not a vertebrate
      innovation. No invertebrate cartilage mineralizes in vivo, although some can be
      induced to mineralize in vitro. Mineralization of cartilage in vivo is a
      vertebrate innovation. Dentine is a novel tissue that only forms from neural
      crest cells. Bone is a vertebrate innovation but not one exclusive to the neural
      crest. The developmental processes responsible for the neural crest and for these
      skeletal tissues did not arise de novo with the vertebrates. Novelty/innovation
      results from tinkering with existing processes, from the flexibility that arises
      from modifications of existing gene networks, and from the selective advantage
      provided by gene duplications or modifications.

PMID- 15968684
TI  - How the turtle forms its shell: a paracrine hypothesis of carapace formation.
AB  - We propose a two-step model for the evolutionary origin of the turtle shell. We
      show here that the carapacial ridge (CR) is critical for the entry of the ribs
      into the dorsal dermis. Moreover, we demonstrate that the maintenance of the CR
      and its ability to attract the migrating rib precursor cells depend upon
      fibroblast growth factor (FGF) signaling. Inhibitors of FGF allow the CR to
      degenerate, with the consequent migration of ribs along the ventral body wall.
      Beads containing FGF10 can rearrange rib migration in the chick, suggesting that
      the CR FGF10 plays an important role in attracting the rib rudiments. The co
      ordinated growth of the carapacial plate and the ribs may be a positive feedback
      loop (similar to that of the limbs) caused by the induction of Fgf8 in the distal
      tips of the ribs by the FGF10-secreting mesenchyme of the CR. Once in the dermis,
      the ribs undergo endochrondral ossification. We provide evidence that the ribs
      act as signaling centers for the dermal ossification and that this ossification
      is due to bone morphogenetic proteins secreted by the rib. Thus, once the ribs
      are within the dermis, the ossification of the dermis is not difficult to
      achieve. This relatively rapid means of carapace formation would allow for the
      appearance of turtles in the fossil record without obvious intermediates.

PMID- 15968685
TI  - First results of triple-modality treatment combining radiotherapy, chemotherapy,
      and hyperthermia for the treatment of patients with stage IIB, III, and IVA
      cervical carcinoma.
AB  - BACKGROUND: Patients with advanced cervical carcinoma are treated routinely with
      radiotherapy and cisplatin-containing chemotherapy. It has been shown that
      hyperthermia can improve the results of both radiotherapy and cisplatin. In the
      current study, the feasibility and efficacy of the combination of all three
      modalities was studied in previously untreated patients with cervical carcinoma.
      METHODS: Patients with advanced cervical carcinoma were registered prospectively
      in the U.S., Norway, and the Netherlands. External-beam radiotherapy and
      brachytherapy were administered for a biologically effective dose > or = 86.7
      gray. At least 4 courses of weekly cisplatin (40 mg/m(2)) and 4 sessions of
      weekly locoregional hyperthermia were added to radiotherapy. RESULTS: Sixty-eight
      patients with a median age of 45 years were enrolled. Full-dose radiotherapy was
      delivered to all patients according to plan. At least 4 courses of chemotherapy
      were received by 97% of patients, and at least 4 courses of hyperthermia
      treatment were received by 93% of patients. Toxicity was fully comparable to that
      described for chemoradiotherapy alone, and the median total treatment time was 45
      days. Complete remission was achieved by 61 patients (90%). After a median follow
      up of 538 days, 74% of patients remained alive without signs of recurrence, and
      the overall survival rate was 84%. CONCLUSIONS: The combination of full-dose
      radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a
      multicenter international setting among patients with advanced cervical
      carcinoma. A Phase III study comparing this novel triplet with standard
      chemoradiation, designed to show at least a 15% improvement in overall survival,
      has been launched.

PMID- 15968686
TI  - Predictors of systemic recurrence and disease-specific survival after ipsilateral
      breast tumor recurrence.
AB  - BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor
      recurrence (IBTR) after breast-conserving therapy (BCT) is an independent
      predictor of systemic recurrence and disease-specific survival (DSS). However,
      only a subgroup of patients with IBTR develop systemic recurrences. Therefore,
      the management of isolated IBTR remains controversial. The objective of the
      current study was to identify determinants of systemic recurrence and DSS after
      IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III
      breast carcinoma between 1971 and 1996 and who subsequently developed isolated
      IBTR were reviewed. Clinicopathologic factors were studied using univariate and
      multivariate analyses for their association with DSS and the development of
      systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months.
      At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic
      recurrence. Initial lymph node status was the strongest predictor of systemic
      recurrence according to the a univariate analysis (P = 0.001). Other significant
      factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR
      < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the
      recurrent tumor, and skin involvement at IBTR. In a multivariate logistic
      regression analysis, initially positive lymph node status (relative risk [RR],
      5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement
      at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors
      of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and
      68%, respectively. In a multivariate Cox proportional hazards model analysis,
      only LVI in the recurrent tumor was found to be an independent predictor of DSS
      (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had
      lymph node-positive disease or skin involvement or LVI at IBTR represented
      especially high-risk groups that warranted consideration for aggressive, systemic
      treatment and novel, targeted therapies after IBTR. Determinants of prognosis
      after IBTR should be taken into account when evaluating the need for further
      systemic therapy and designing risk-stratified clinical trials.

PMID- 15968687
TI  - Clinical management of osteoporosis in women with a history of breast carcinoma.
AB  - Osteoporosis is a skeletal disorder that is characterized by low bone mass and
      compromised bone strength. Fractures are the clinically important consequence of
      osteoporosis and result not only in disability but also in excess mortality.
      Women who have a history of breast carcinoma may represent a unique population
      for whom screening and treatment for osteoporosis should be modified. A review of
      the English literature was performed that included original, review, consensus,
      and statement articles that were identified through Medline or National
      Institutes of Health-related links. According to the literature, osteoporosis
      constitutes a major public health problem. Approximately 55% of the U.S.
      population > or = 50 years of age has low bone mass (osteopenia or osteoporosis).
      Annually, > 200,000 women in the U.S. are diagnosed with breast carcinoma. Due to
      the high prevalence rates of both low bone mass and breast carcinoma in women,
      these two diseases commonly coexist in the same individuals. Women with a history
      of breast carcinoma may be at increased risk of developing bone loss and
      fragility fractures as a consequence of antineoplastic therapies. The majority of
      women treated for early-stage breast carcinoma do not develop recurrences, as a
      result of recent advances in therapy. Ensuring the diagnosis, prevention, and
      treatment of long-term toxicities and comorbid conditions like osteoporosis in
      breast carcinoma survivors is a serious concern and is of increasing importance.
      In this article, the authors address the evaluation and treatment of osteoporosis
      in women who have a history of early-stage breast carcinoma.

PMID- 15968688
TI  - Chromosome abnormalities in juxtaglomerular cell tumors.
AB  - BACKGROUND: Juxtaglomerular cell tumors (JGCT; also known as reninomas) are
      considered benign tumors of the kidney, although there have been reports of both
      malignant behavior and a JGCT-related death. The clinicopathologic features of
      these rare tumors are well established, whereas nothing is known about their
      cytogenetic characteristics. METHODS: The authors reported the first karyotype of
      a JGCT and also performed comparative genomic hybridization (CGH) and interphase
      fluorescence in situ hybridization (IP-FISH) analyses on the above-mentioned
      tumor as well as on another JGCT from which live cells were not available for
      karyotyping. Both tumors were also examined by electron microscopy and
      immunohistochemistry. RESULTS: The karyotype was 57 approximately 64,XX,-X,-1,-4,
      6,-9,+10,-11,-13,-14, -15,+20,-22[cp10]/60 approximately 61,idem,
      add(19)(p13)[cp2]/46,XX[3]. The IP-FISH results were in accordance with the
      karyotypic findings for the first tumor, whereas Tumor 2 was found to be diploid
      for most investigated chromosomes, except for trisomy for chromosomes 4 and 10
      and monosomy for chromosomes 9 and X. By CGH, gain of chromosomes 10 and 20 but
      no losses were detected for Tumor 1, whereas for Tumor 2, gain of chromosomes 4
      and 10 as well as loss of chromosomes 9 and X and most of chromosome arm 11q were
      found. The immunohistochemical profiles were identical. Both tumors were positive
      for vimentin and CD34, focally positive for smooth muscle actin, and negative for
      cytokeratin, CD31, and actin. CONCLUSIONS: Gain of chromosome 10, as well as loss
      of chromosomes 9 and X and most of chromosome arm 11q, might be important
      pathogenetic events in JGCT.

PMID- 15968689
TI  - Ifosfamide/liposomal daunorubicin is a well tolerated and active first-line
      chemotherapy regimen in advanced soft tissue sarcoma: results of a phase II
      study.
AB  - BACKGROUND: The anthracycline/ifosfamide combination is the most effective
      chemotherapy in soft tissue sarcoma. To improve the tolerability and potential
      efficacy of this combination, the authors combined a moderate dose of continuous
      infusion ifosfamide with liposomal daunorubicin (L-Dauno). METHODS: In a single
      arm, Phase II study, 40 patients with a median age of 57 years (range, 19-78
      years) were enrolled. Of these, 35 patients were treated with first-line
      chemotherapy. The treatment regimen was comprised of ifosfamide at a dose of 5
      g/m(2) over 24 hours and L-Dauno at a dose of 100 mg/m(2) every 4 weeks with
      granulocyte-colony-stimulating factor support. RESULTS: Eleven (31%) of 35
      anthracycline/ifosfamide-naive patients achieved a partial/complete response, 6
      patients (17%) had stable disease, and 13 patients (37%) had disease progression.
      Three patients were not evaluable, and there were two intermittent deaths. The
      median time to disease progression was 6 months, the median overall survival was
      14 months, and the median time to treatment failure was 15 months. Toxicity was
      tolerable. CONCLUSIONS: The combination of Ifosfamide and L-Dauno was found to be
      a highly active chemotherapy regimen for first-line treatment of soft tissue
      sarcoma. Therefore, we believe randomized studies with this regimen are
      warranted.

PMID- 15968690
TI  - Sperm cryopreservation before cancer chemotherapy helps in the emotional battle
      against cancer.
AB  - BACKGROUND: Sperm cryopreservation before cancer chemotherapy is available for
      young patients with cancer. However, few patients bank their sperm. The authors
      evaluated by questionnaire the psychological impact of sperm cryopreservation.
      METHODS: The authors cryopreserved the sperm of 111 patients with cancer for free
      at the Yokohama City University (Yokohama, Japan). For the current study,
      questionnaires were mailed to 66 patients whose sperm had been cryopreserved.
      Fifty-one patients (77.3%) with testicular carcinomas (n = 24), leukemia or
      malignant lymphoma (n = 19), or other cancers (n = 8) answered the questionnaire.
      The average age at collection and the period of sperm cryopreservation were 30.1
      +/- 6.0 (mean +/- standard deviation) and 3.3 +/- 2.2 years, respectively.
      RESULTS: Many patients were informed of the deleterious effects of cancer
      chemotherapy and worried about infertility in the future. However, only half of
      the patients banked their sperm on their own initiative. Other patients followed
      their physician's instruction. Eighty percent of patients replied that sperm
      cryopreservation helped in the battle against cancer. Sperm banking especially
      was found to encourage every patient who banked sperm on their own initiative.
      After cancer chemotherapy, 70% of patients wanted to have a child. However, 60%
      of patients were worried about infertility in spite of having their sperm
      cryopreserved. No patients wanted to use cryopreserved sperm for fathering
      children if their spermatogenesis was restored. Sperm cryopreservation
      invigorated many patients with cancer after cancer treatments. The majority of
      patients recommended sperm cryopreservation to other cancer patients.
      CONCLUSIONS: Sperm cryopreservation encouraged young patients with cancer during
      and after cancer treatment. It should be recommended for all young patients with
      cancer. However, sperm cryopreservation did not eliminate their fear of
      infertility.

PMID- 15968691
TI  - The clinical use of staging bone scan in patients with breast carcinoma:
      reevaluation by the 2003 American Joint Committee on Cancer staging system.
AB  - BACKGROUND: Using the new 2003 American Joint Committee on Cancer (AJCC) staging
      system, the authors evaluated the usefulness of the staging bone scan in patients
      with primary breast carcinoma. METHODS: The authors examined 1939 patients with
      primary breast carcinoma for staging bone scan who were treated at a single
      institution. Pathologic stage was assigned retrospectively according to the 1988
      and the 2003 AJCC staging systems. RESULTS: Bone metastasis rates were 0.7% (4 of
      586) for patients with Stage I disease, 0.7% (5 of 699) for patients with Stage
      IIA disease, 2.1% (10 of 479) for patients with Stage IIB disease, 4.5% (7 of
      154) for patients with Stage IIIA disease, and 10.5% (2 of 19) for patients with
      Stage IIIB disease according to the 1988 AJCC staging system. The authors found a
      significant difference in the bone metastasis rate between patients with Stages
      IIA and IIB disease in the 1988 staging system (P = 0.039). Reevaluating the
      patients by the 2003 system resulted in significant upstaging, especially for
      patients with Stage II/III disease. According to the 2003 staging system, bone
      metastasis rates were 0.7% (4 of 586) for patients with Stage I disease, 0.6% (4
      of 648) for patients with Stage IIA disease, 0.6% (2 of 310) for patients with
      Stage IIB disease, 4.0% (9 of 225) for patients with Stage IIIA disease, 16.7% (2
      of 12) for patients with Stage IIIB disease, and 4.4% (7 of 158) for patients
      with Stage IIIC disease. It was noteworthy that there was a significant
      difference between Stages IIB and IIIA in the 2003 staging system (P = 0.010).
      CONCLUSIONS: Stage reclassification using the new AJCC staging system resulted in
      upstaging of high-risk patients, as well as a significant decrease in the bone
      metastasis rate in patients with Stage IIB breast carcinoma. Considering the cost
      effectiveness of staging bone scan, the data suggested that it was of little
      value for patients with Stage I and II breast carcinoma, but was highly
      recommended for patients with worse than Stage III disease by the new 2003
      staging system.

PMID- 15968692
TI  - Psychologic and social sequelae of secondary lymphedema: a review.
AB  - BACKGROUND: The psychological and social sequelae of secondary lymphedema (SLE)
      have been an underrecognized and little-researched complication of treatment for
      breast carcinoma. The reported incidence and prevalence of SLE varied widely (0
      48%). Reported reasons for the differences are related to the lack of standard
      diagnostic and universal assessment criteria. METHODS: A comprehensive,
      computerized search was performed. All combinations of the following keywords
      were used: arm lymphedema, arm swelling, breast cancer, psychological and social,
      and quality of life (QOL). Eighteen studies were identified. RESULTS: The
      literature supported the view that SLE leads to psychological and social
      sequelae. Psychological sequelae included frustration, distress, depression and
      anxiety. Social sequelae comprised changes in role function, lack of social
      support and pain and disability. Pain was a significant predictor of
      psychological and social morbidity. These experiences resulted in diminution of
      QOL, particularly psychological and social health. This was particularly
      worrisome because women must attend daily to the precautions and treatments for
      SLE. CONCLUSIONS: Researchers should use psychological and social measures along
      with physiologic parameters when evaluating the impacts of SLE. Clinicians should
      work to develop standardized primary prevention programs and limb circumference
      should be measured at the time of breast carcinoma diagnosis. Gaps in knowledge
      related to intra/interethnic diversity, poverty, and comorbidities of women with
      breast carcinoma-related SLE need to be explored. The combined efforts of
      researchers and clinicians would reinforce awareness and knowledge for women at
      risk and provide important baseline data for research and practice.

PMID- 15968693
TI  - Locking and unlocking of polyelectrolyte brushes: toward the fabrication of
      chemically controlled nanoactuators.

PMID- 15968694
TI  - A recyclable catalytic system based on a temperature-responsive catalyst.

PMID- 15968695
TI  - Host-guest interactions: design strategy and structure of an unusual cobalt cage
      that encapsulates a tetrafluoroborate anion.

PMID- 15968696
TI  - Br2(X) microsolvation in helium clusters: effect of the interaction on the
      quantum solvent density distribution.
AB  - The Born-Oppenheimer potential energy surface for the Br2(X) molecule interacting
      with a varying number of 4He bosons is constructed following two different
      schemes which employ either a full ab initio evaluation of the Br2-He interaction
      forces or an estimate of the latter through an empirical model. Both descriptions
      are employed by carrying out diffusion Monte Carlo (DMC) calculations of the
      ground-state energies and quantum wavefunctions for Br2-(He)n clusters with n up
      to 24. The results clearly indicate, for both interactions, the occurrence of the
      full solvation of the molecular dopant within the quantum bosonic "solvent" but
      also show differences between the two models in terms of the expected density
      distributions of the surrounding particles within the shorter-range region that
      makes up the clusters with smaller n values. Our calculations also show that such
      differences become insignificant for the larger 4He clusters surrounding the Br2
      molecule, where density profiles and bulk behaviour are chiefly driven by the
      solvent structure, once n values reach the region of 15-20 adatoms.

PMID- 15968697
TI  - Adsorption of [D2]methanol on Ru(001)--O surfaces: the influence of preadsorbed
      oxygen on the methoxide geometry.
AB  - The influence of oxygen precoverage on the bonding geometry of methoxide on
      Ru(001) was studied using the isotopically labeled molecule CHD2OH by reflection
      absorption infrared spectroscopy (RAIRS). This molecule is an excellent model
      because the vibrational spectra of CHD2O- may be unambiguously correlated with
      the adsorption configuration. For Ru(001)--O layers with an effective oxygen
      coverage (theta0) between 0.25 and 0.6 ML (ML=monolayer), the influence of the
      oxygen precoverage was shown to vary with the initial methanol exposure. For an
      extremely low dose of [D2]methanol (0.01 L; L=Langmuir, 1 L=10(-6) torr s), at 90
      K, no oxygen-coverage effects were detected on the geometry of [D2]methoxide: it
      adsorbs in an upright orientation (pseudo-C(3v) local symmetry), just as on clean
      Ru(001). An increase in the methanol exposure to 0.1 L, at the same temperature,
      results in the formation of a disordered layer of tilted methoxide: for
      theta(O)=0.25 ML, C(s)/C1 and intrinsic C1 configurations are present on the
      surface, whereas for theta(O)> or =0.5 ML, only the former species were
      identified. The thermal activation of these tilted layers to 105 K results in a
      lower coverage of upright methoxide for any oxygen precoverage, coadsorbed with
      decomposition products, as confirmed by the detection of adsorbed formaldehyde
      and, on the denser oxygen layer (theta(O)=0.6 ML), formate. The influence of the
      oxygen precoverage becomes determinant when annealing a [D2]methanol multilayer
      to 105 K: for theta(O)=0.25 ML, the RAIR spectrum correlates with a disordered
      layer of tilted methoxide and formaldehyde, whereas for theta(O)=0.6 ML upright
      methoxide, formate, and carbon monoxide were identified. On clean Ru(001), for
      methanol exposures > or =0.1 L, the C(3v) methoxide configuration was never
      attained upon thermal activation.

PMID- 15968698
TI  - Assessment of density functionals for the high-spin/low-spin energy difference in
      the low-spin iron(II) tris(2,2'-bipyridine) complex.
AB  - In the iron(II) low-spin complex [Fe(bpy)3]2+, the zero-point energy difference
      between the 5T2g(t4(2g)e2g) high-spin and the 1A(1g)(t(6)2g) low-spin states,
      Delta(E)0HL, is estimated to lie in the range of 2500-5000 cm(-1). This estimate
      is based on the low-temperature dynamics of the high-spin-->low-spin relaxation
      following the light-induced population of the high-spin state and on the
      assumption that the bond-length difference between the two states Delta(r)HL is
      equal to the average value of approximately 0.2 A, as found experimentally for
      the spin-crossover system. Calculations based on density functional theory (DFT)
      validate the structural assumption insofar as the low-spin-state optimised
      geometries are found to be in very good agreement with the experimental X-ray
      structure of the complex and the predicted high-spin geometries are all very
      close to one another for a whole series of common GGA (PB86, PW91, PBE, RPBE) and
      hybrid (B3LYP, B3LYP*, PBE1PBE) functionals. This confirmation of the structural
      assumption underlying the estimation of Delta(E)0HL from experimental relaxation
      rate constants permits us to use this value to assess the ability of the density
      functionals for the calculation of the energy difference between the HS and LS
      states. Since the different functionals give values from -1000 to 12000 cm(-1),
      the comparison of the calculated values with the experimental estimate thus
      provides a stringent criterion for the performance of a given functional. Based
      on this comparison the RPBE and B3LYP* functionals give the best agreement with
      experiment.

PMID- 15968699
TI  - Radiolysis of confined water: molecular hydrogen formation.
AB  - The formation of molecular hydrogen in the radiolysis of water confined in
      nanoscale pores of well-characterised porous silica glasses and mesoporous
      molecular sieves (MCM-41) is examined. The comparison of dihydrogen formation by
      irradiation of both materials, dry and hydrated, shows that a large part of the
      H2 comes from the surface of the material. The radiolytic yields, G(H2)=(3+/
      0.5)x10(-7) mol J(-1), calculated using the total energy deposited in the
      material and the water, are only slightly affected by the degree of hydration of
      the material and by the pore size. These yields are also not modified by the
      presence of hydroxyl radical scavengers. This observation proves that the back
      reaction between H2 and HO(.) is inoperative in such confined environments.
      Furthermore, the large amount of H2 produced in the presence of different
      concentrated scavengers of the hydrated electron and its precursor suggests that
      these two species are far from being the only species responsible for the H2
      formation. Our results show that the radiolytic phenomena that occur in water
      confined in nanoporous silica are dramatically different to those in bulk water,
      suggesting the need to investigate further the chemical reactivity in this type
      of environment.

PMID- 15968700
TI  - Ab initio studies of electron acceptor-donor interactions with blue- and red
      shifted hydrogen bonds.
AB  - The features of blue- and red-shifted electron acceptor-donor (ACH/B) hydrogen
      bonds have been compared by using quantum chemical calculations. The geometry,
      the interaction energy and the vibrational frequencies of both blue- (ACH=F3CH,
      Cl3CH with B=FCD3) and red-shifted (ACH=F3CH, Cl3CH with B=NH3 and ACH=CH3CCH
      with B=FCD3, NH3) complexes were obtained by using ab initio MP2(Full)/6
      31+G(d,p) calculations with the a priori basis-set superposition error (BSSE)
      correction method. One-dimensional potential energy and dipole moment functions
      of the dimensionless normal coordinate Q1, corresponding to the CH stretching
      mode of ACH, have been compared for both types of complexes. Contributions of
      separate components of the interaction energy to the frequency shift and the
      effect of electron charge transfer were examined for a set of intermolecular
      distances by using the symmetry-adapted perturbation theory (SAPT) approach and
      natural bond orbitals (NBO) population analysis.

PMID- 15968701
TI  - Enhanced operational stability of the up-conversion fluorescence in films of
      palladium-porphyrin end-capped poly(pentaphenylene).

PMID- 15968702
TI  - Mechanism of hierarchical porosity development in MFI zeolites by desilication:
      the role of aluminium as a pore-directing agent.
AB  - The role of the concentration and the nature of aluminium in the creation of
      hierarchical porosity in both commercial and synthesized MFI zeolites have been
      investigated through controlled mesoporosity development by desilication in
      alkaline medium. Framework aluminium controls the process of framework silicon
      extraction and makes desilication selective towards intracrystalline mesopore
      formation. An optimal molar Si/Al ratio in the range 25-50 has been identified;
      this leads to an optimal mesoporosity centred around 10 nm and mesopore surface
      areas of up to 235 m(2) g(-1) while preserving the intrinsic crystalline and
      acidic properties. At lower framework Si/Al ratios the relatively high Al content
      inhibits Si extraction and hardly any mesopores are created, while in highly
      siliceous ZSM-5 unselective extraction of framework Si induces formation of large
      pores. The existence of framework Al sites in different T positions that are more
      or less susceptible to the alkaline treatment, and the occurrence of re
      alumination, are tentative explanations for the remarkable behaviour of Al in the
      desilication process. The presence of substantial extra framework Al, obtained by
      steam treatment, inhibits Si extraction and related mesopore formation; this is
      attributed to re-alumination of the extraframework Al species during the alkaline
      treatment. Removal of extraframework Al species by mild oxalic acid treatment
      restores susceptibility to desilication, which is accompanied by formation of
      larger mesopores due to the enhanced Si/Al ratio in the acid-treated zeolite.

PMID- 15968703
TI  - A low-cost biofuel cell with pH-dependent power output based on porous carbon as
      matrix.
AB  - A glucose/O2 biofuel cell (BFC) possessing a pH-dependent power output was
      fabricated by taking porous carbon (PC) as the matrix to load glucose oxidase or
      fungi laccase as the catalysts. The electrolytes in the anode and cathode
      compartments contain ferrocene monocarboxylic acid and 2,2'-azino-bis-(3
      ethylbenzthiazoline-6-sulfonic acid) diammonium salt as the mediators,
      respectively. The power of the BFC was enhanced significantly by using PC as the
      matrix, rather than glassy carbon electrode. Additionally, the power output of
      the BFC decreases as the pH of the solution increases from 4.0 to 7.0, which
      provides a simple and efficient method to achieve the required power output. More
      importantly, the BFC can operate at pH 6.0, and even at pH 7.0, which overcomes
      the requirement for cathode solutions of pH<5.0 when using fungi laccase as a
      catalyst. Operation of the BFC at neutral pH may provide a means to power medical
      devices implanted in physiological systems. The facile and low-cost fabrication
      of this BFC may enable its development for other applications.

PMID- 15968704
TI  - Reversible substrate anchoring: NC-SPOS as a sustainable approach to solid
      supported organic synthesis.

PMID- 15968705
TI  - Dietary supplement of isohumulones inhibits the formation of aberrant crypt foci
      with a concomitant decrease in prostaglandin E2 level in rat colon.
AB  - Male Fischer 344 rats were subcutaneously injected with azoxymethane (AOM) twice
      weekly at a dose of 15 mg/kg and were fed with freeze-dried (FD) samples of beer
      brewed without hops (non-hops beer), beer with hops at 4 times the amount of
      regular lager beer (x 4-hops beer), and isomerized hop extract (IHE) for the
      whole experimental period (I/PI) or for the post-initiation period (PI) only.
      Feeding FD beer samples at a dose of 1% significantly decreased the number of
      aberrant cryp foci (ACF) in the PI protocol over five weeks.x4-hops beer showed
      stronger inhibitory effects on the development of the numbers of aberrant crypts
      per focus and large ACF with four or more crypts than non-hops beer. Feeding IHE
      to rats at a dose of 0.01% or 0.05% in either the I/PI or PI experiment
      significantly reduced the numbers of ACF. Prostaglandin E2 (PGE2) levels in
      colonic mucosa of AOM-treated rats were significantly reduced by feeding of IHE.
      PGE2 production induced by lipopolysaccharide/interferon-gamma (LPS/IFN-gamma) in
      RAW264.7 cells was also reduced by treatment with IHE and isohumulone in a dose
      dependent manner. These observations suggest that isohumulones show
      chemopreventive effects on ACF formation in rat colon by inhibiting the
      production of PGE2.

PMID- 15968706
TI  - Debtor education, financial literacy, and pending bankruptcy legislation.
AB  - This paper reports on an evaluation of a financial education-training program for
      residents of New York who had filed for bankruptcy. Over 400 individuals divided
      into three groups (trained debtors, untrained debtors, and non-debtors) completed
      identical questionnaires approximately three months apart. Trained debtors took
      the pretest before training and the post-test after training. Results revealed
      that trained debtors' financial knowledge increased after training compared with
      untrained and non-debtors. Trained debtors showed more negative attitudes towards
      unnecessary spending compared with the other two groups and reported less
      intention to buy than non-debtors reported. Self-reported behaviors showed
      significant changes in the desired direction for trained debtors' use of credit
      cards (i.e. number owned, purchases, and balance amount), paying bills,
      budgeting, and borrowing from predatory lenders. Implications for pending
      legislation are discussed.

PMID- 15968707
TI  - The problem behavior model: the development of a stalkers clinic and a
      threateners clinic.
AB  - Traditionally, forensic mental health services have focused on the assessment and
      treatment of offenders with serious mental disorders. In recent years, there has
      been growing recognition that forensic clinicians have an important role to play
      for those offenders who engage in criminal acts driven by psychological or/and
      social problems, which may, or may not, occur in conjunction with a major mental
      disorder. This is especially true for specific offenses such as stalking and
      threatening. This article describes the innovation of the problem behavior model.
      This model uses a reductionist approach and the nexus between psychiatry and
      psychology to address the complex phenomena associated with specific problem
      behaviors that often culminate in offenses. The model is illustrated by
      describing the development of specialist clinics for the problem behaviors of
      stalking and threatening.

PMID- 15968708
TI  - What policymakers need and must demand from research regarding the employment
      rate of persons with disabilities.
AB  - Enabling persons with disabilities to prepare for and engage in gainful
      employment has become a priority concern in U.S. society. As a result, federal
      and state policymakers are adopting employment-related initiatives designed to
      enhance the employment rate of persons with disabilities. Policymakers need
      credible evidence in order to assess and reform these initiatives. This
      recognized need, however, begs the question of what constitutes 'credible
      evidence.' Of particular concern in the disability policy arena is the debate
      over the types of conclusion about employment rates that can and cannot be drawn
      from analyses of national survey data sets. This article connects standard
      research methodology concepts with the complexities of evaluating disability
      policy to help stakeholders appreciate the issues involved in this debate. This
      appreciation can help policymakers (1) recognize unwarranted cause-and-effect
      conclusions based solely on existing national survey data and (2) demand better
      data and stronger research designs to complement the potential over-reliance on
      correlational studies using problematic survey data to estimate policy impacts.
      To this end, the article concludes with a practical framework with a checklist
      for assessing the adequacy of research regarding the employment rate of persons
      with disabilities.

PMID- 15968709
TI  - Is death row obsolete? A decade of mainstreaming death-sentenced inmates in
      Missouri.
AB  - Death-sentenced inmates in Missouri have been integrated or "mainstreamed" into
      the general population of the Potosi Correctional Center since 1991. By comparing
      the rate of violent misconduct among these mainstreamed death-sentenced inmates
      with that of the life-without-parole and parole eligible inmates under fully
      integrated conditions of confinement, this study provides the first empirical
      (statistical) evaluation of this innovative alternative to segregated death row
      confinement. The mainstreamed death-sentenced inmates committed no inmate or
      staff homicides, or attempted homicides. Comparison of their rates of
      institutional violence revealed frequencies that were similar to those of life
      without-parole inmates, and well below those of fellow inmates who were sentenced
      to parole eligible terms. These findings cast serious doubt on the security
      driven assumptions that have typified the segregation of death-sentenced inmates
      and have dictated highly restrictive confinement policies for this group. A
      conclusion that death-sentenced inmates can be safely integrated into a general
      prison population has significant implications for allocation of scarce fiscal
      resources and correctional staff, as well as for inmate mental health,
      particularly given the extended tenure that death-sentenced inmates typically
      serve between sentencing and relief/execution.

PMID- 15968710
TI  - Juror reactions to jury duty: perceptions of the system and potential stressors.
AB  - Jurors were surveyed on their general perceptions of the court system and factors
      that may cause stress immediately after trial, after participating in a post
      trial debriefing, and a month after trial. Jurors had an overall positive view of
      the court system but did report some perceived inequities. The two most stressful
      elements of jury duty were related to the complexity of the trial and the
      decision-making involved in the trial, although jurors reported low levels of
      stress overall. Women reported more stress than men, and trial characteristics
      such as trial length also affected stress levels. The debriefing intervention was
      perceived as helpful, but jurors' stress levels were similar at pre- and post
      debriefing. Finally, although stress on some measures was lower at the 1 month
      follow-up, this reduction was not moderated by whether or not jurors received the
      debriefing.

PMID- 15968711
TI  - Survey on the future organisation of first-trimester ultrasound screening in
      Flanders, Belgium.

PMID- 15968712
TI  - Bioequivalence evaluation of two brands of fluoxetine 20 mg capsules (Flutin and
      Prozac) in healthy human volunteers.
AB  - A bioequivalence study of two oral formulations of 20 mg fluoxetine was carried
      out in 24 healthy volunteers following a single dose, two-sequence, crossover
      randomized design at International Pharmaceutical Research Centre (IPRC), Amman,
      Jordan. The two formulations were Flutin capsules (Julphar, UAE) as test and
      Prozac capsules (Eli Lilly, UK) as reference product. Test and reference capsules
      were administered to each subject after an overnight fasting on two treatment
      days separated by a 28 day washout period. After dosing, serial blood samples
      were collected for a period of 360 h. Plasma harvested from blood was analysed
      for fluoxetine by a sensitive, reproducible and accurate LC-MS method. Various
      pharmacokinetic parameters including AUC(0-t), AUC(0-infinity), C(max), T(max),
      T(1/2), and lambda(Z) were determined from plasma concentrations for both
      formulations and found to be in good agreement with reported values. AUC(0-t),
      AUC(0-infinity) and C(max) were tested for bioequivalence after log
      transformation of data. No significant difference was found based on ANOVA; 90%
      confidence interval (94.60%-106.41% for AUC(0-t), 94.6%-108.14% for AUC(0
      infinity); 91.88%-103.65% for C(max)) for test/reference ratio of these
      parameters were found within FDA acceptance range of 80%-125%. Based on these
      statistical inferences, it was concluded that Flutin is bioequivalent to Prozac
      and can be used interchangeably in medical practice.

PMID- 15968713
TI  - Pharmacokinetics of Amiodarone in hyperlipidemic and simulated high fat-meal rat
      models.
AB  - The objective of this study was to examine the effect of a high fat meal and
      hyperlipidemia on the pharmacokinetic behavior of amiodarone. To evaluate these
      effects, single doses of amiodarone were administered to rats i.v. (25 mg/kg) or
      orally (50 mg/kg). Some rats were rendered hyperlipidemic by intraperitoneal
      doses of poloxamer 407 followed by amiodarone i.v. In other normolipidemic rats,
      amiodarone was administered i.v. in a fasted state or after the administration of
      1% cholesterol in peanut oil. Amiodarone plasma concentrations were considerably
      (>11-fold) increased in hyperlipidemia. Substantial decreases were noted in the
      clearance, volume of distribution and unbound fraction (11.6, 23 and 24.7-fold,
      respectively) in plasma of hyperlipidemic rats. Oral lipid caused a significant
      increase in plasma AUC(0-infinity) (1.38-fold) and a significant decrease in
      clearance (1.5-fold) of amiodarone after intravenous doses. Oral consumption of
      1% cholesterol in peanut oil significantly increased the plasma AUC (1.83-fold)
      and bioavailability of amiodarone (1.31-fold) after oral doses. In determining
      oral bioavailability of lipophilic drugs such as amiodarone in food effect
      studies, in addition to the increase in absorption of drugs, other factors such
      as a decrease in clearance due to increases in lipoprotein levels should be taken
      into account.

PMID- 15968714
TI  - Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1
      and Kazakh's esophageal squamous cell cancer in Xinjiang, China.
AB  - AIM: To analyze the relationship between genetic polymorphisms of metabolizing
      enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in China.
      METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S
      transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and
      restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's
      patients with esophageal cancer (EC) and 104 non-cancer controls. RESULTS: The
      frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with
      cancer (77.9%) than in control subjects (24.0%) (P<0.05; OR, 11.13; 95%CI, 5.84
      21.22). The difference of GSTM1 null was significantly more frequent in the
      cancer (34.6%) vs the control group (3.8%) (P<0.05; OR, 13.24; 95%CI, 4.50
      38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1
      genotypes increased the risk for cancer (P<0.05; OR, 13.42; 95%CI, 6.29-28.3).
      CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically
      susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1
      of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover,
      CYP2E1 wild type (c1/c1) increased the susceptibility to ESCC risk in Kazakh
      individuals with GSTM1 presence genotype.

PMID- 15968715
TI  - Anticancer effect and apoptosis induction of gambogic acid in human gastric
      cancer line BGC-823.
AB  - AIM: To investigate the anticancer effect of a traditional Chinese medicine
      gambogic acid (GA) in human gastric cancer line BGC-823 and further study the
      mechanism of apoptosis induction of GA. METHODS: Low differential human gastric
      cancer line BGC-823 were treated with GA at different doses and different times,
      the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC
      823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay.
      And T/C (%) was chosen to detect the inhibition of GA on human gastric
      adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts
      was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA
      fragmentation assay. To further determine the molecular mechanism of apoptosis
      induced by GA, the changes on the expression of bcl-2 and bax genes were detected
      by RT-PCR. RESULTS: After incubation with GA, low differential human gastric
      cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After
      these cells was exposed to GA for 24, 48 and 72 h, the IC(50) value were 1.02+/
      0.05, 1.41+/-0.20 and 1.14+/-0.19 micromol/L, respectively. Apoptosis in BGC-823
      cells induced by GA was observed by Annexin-V/PI doubling staining flow cytometry
      assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%,
      respectively, when cells were incubated with 1.2 micromol/L GA for 48 and 72 h.
      T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts
      was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis
      induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude
      mice xenografts. The increase of bax gene and the decrease of bc1-2 gene
      expressions were found by RT-PCR. CONCLUSION: The inhibition of GA on human
      gastric cancer line BGC-823 was confirmed. This effect connects with the inducing
      apoptosis in BGC-823 cells and the molecular mechanism might be related to the
      reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of
      the expression of apoptosis-regulated gene bax. The result was also confirmed in
      vivo.

PMID- 15968716
TI  - Preparation of immunomagnetic iron-dextran nanoparticles and application in rapid
      isolation of E.coli O157:H7 from foods.
AB  - AIM: To prepare a kind of magnetic iron-dextran nanoparticles that was coated
      with anti-E.coli O157:H7 IgG, analyze its application conditions, and try to use
      it to isolate E.coli O157:H7 from foods. METHODS: Magnetic iron-dextran
      nanoparticles were prepared by the reaction of a mixture of ferric and ferrous
      ions with dextran polymers under alkaline conditions. The particles were coated
      with antiserum against E.coli O157:H7 by the periodate oxidation-borohydride
      reduction procedure. The oxidation time, amount of antibody coating the
      particles, amount of nanoparticles, incubation time and isolation time were
      varied to determine their effects on recovery of the organisms. Finally, the
      optimum conditions for isolating E.coli O157:H7 from food samples were
      established. RESULTS: E.coli O157:H7 can be isolated from samples within 15 min
      with the sensitivity of 10(1) CFU/mL or even less. In the presence of 10(8)
      CFU/mL of other organisms, the sensitivity is 10(1)-10(2) CFU/mL. Nonspecific
      binding of other bacteria to the particles was not observed. Two and a half hours
      of enrichment is enough for the particles to detect the target from the food
      samples inoculated with 1 CFU/g. CONCLUSION: Isolation of target bacteria by
      immunomagnetic nanoparticles is an efficient method with high sensitivity and
      specificity. The technique is so simple that it can be operated in lab and field
      even by untrained personnel.

PMID- 15968717
TI  - Changes of gastrointestinal myoelectric activity and bile acid pool size after
      cholecystectomy in guinea pigs.
AB  - AIM: To investigate the bile acid pool size after cholecystectomy whether or not
      correlated to the gastrointestinal migrating myoelectric complex (MMC) in guinea
      pigs. METHODS: Gallbladder motilities were assessed before cholecystectomy.
      Furthermore, we continuously monitored interdigestive gastrointestinal motilities
      using bipolar electrodes in conscious guinea pigs before and after surgery at 4
      wk in standard diet group and high cholesterol diet (cholesterol gallstone)
      group. Total bile acid pool sizes were measured by isotope dilution method at
      meantime. RESULTS: After cholecystectomy, there were parallel falls in duration
      of phase I, II, III and MMC cycle duration but increase in amplitude in the
      guinea pigs with normal gallbladder function, and in the guinea pigs with
      cholesterol stones. However, There were not significantly differences. On the
      other hand, the bile acid pool was definitely small in the GS guinea pigs
      compared to normal guinea pigs and became slightly smaller after cholecystectomy.
      Similarly, bile acid in gallbladder bile, fecal bile acid was slightly increased
      in GS guinea pigs after cholecystectomy, to the same degree as normal. These
      differences, however, were not significant. CONCLUSION: It is concluded that in
      the guinea pigs with normal gallbladder function, and in the guinea pigs with
      cholesterol stones: (1) Cholecystectomy produce a similar but less marked trend
      in bile acid pool; and (2) MMC are linked to enterohepatic circulation of bile
      acids, rather than surgery, which is consistent with changes of the bile acid
      pool size. As a result, gastrointestinal dyskinesia is not involved in occurrence
      of postcholecystectomy syndrome.

PMID- 15968718
TI  - Anti-lipid peroxidation and protection of liver mitochondria against injuries by
      picroside II.
AB  - AIM: To investigate the anti-lipid peroxidation and protection of liver
      mitochondria against injuries in mice with liver damage by picroside II. METHODS:
      Three animal models of liver damage induced by carbon tetrachloride (CCl(4): 0.1
      mL/10 g, ip), D-galactosamine (D-GalN: 500 mg/kg, ip) and acetaminophen (AP: 0.15
      g/kg, ip) were respectively treated with various concentrations of picroside II
      (5, 10, 20 mg/kg, ig). Then we chose the continuously monitoring method
      (recommended by International Clinical Chemistry League) to analyze serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) values, Marland
      method to detect the activity of manganese-superoxide dismutase (SOD) in liver
      mitochondria, TBA colorimetry to determine the content of malonicdialdehyde (MDA)
      in liver tissue, DTNB method to evaluate the activity of glutathioneperoxidase
      (GSH-Px) and Lowry method to detect protein level in liver tissue. Meanwhile,
      effects of picroside II on the activity of ATPase and swelling extent of
      mitochondria in hepatocytes damaged by AP were also evaluated. RESULTS: Picroside
      II could significantly prevent liver toxicity in the three models of liver
      damage. It decreased the high levels of ALT and AST in serum induced by the
      administration of CCl(4), D-GalN and AP, reduced the cellular damage of liver
      markedly, and appeared to be even more potent than the positive control drug of
      biphenyl dimethyl dicarboxylate pilules (DDB). In groups treated with different
      doses of picroside II, compared to the model group, the content of MDA in serum
      decreased evidently, whereas the content of SOD and GSH-Px increased in a dose
      dependent manner, and the difference was statistically significant. Further, in
      the study of AP model, picroside II inhibited AP-induced liver toxicity in mice,
      enhanced the activity of ATPase, improved the swelling extent of mitochondria and
      helped to maintain a normal balance of energy metabolism. CONCLUSION: Picroside
      II can evidently relieve hepatocyte injuries induced by CCl(4), D-GalN and AP,
      help scavenge free radicals, protect normal constructions of mitochondria
      membrane and enhance the activity of ATPase in mitochondria, thereby modulating
      the balance of liver energy metabolism, which might be part of the mechanisms of
      hepatoprotective effects of picroside II.

PMID- 15968719
TI  - Development of Wistar rat model of insulin resistance.
AB  - AIM: To establish a simplified and reliable animal model of insulin resistance
      with low cost in Wistar rats. METHODS: Wistar rats were treated with a high fat
      emulsion by ig for 10 d. Changes of the diets, drinking and body weight were
      monitored every day and insulin resistance was evaluated by hyperinsulinemic
      euglycemic clamp techniques and short insulin tolerance test using capillary
      blood glucose. Morphologic changes of liver, fat, skeletal muscles, and
      pancreatic islets were assessed under light microscope. mRNA expressions of GLUT2
      and alpha-glucosidase in small intestine epithelium, GLUT4 in skeletal muscles
      and Kir6.2 in beta cell of islets were determined by in situ hybridization.
      RESULTS: K(ITT) was smaller in treated animals (4.5+/-0.9) than in untreated
      control Wistar rats (6.8+/-1.5), and so was glucose injection rate. Both
      adipocyte hypertrophy and large pancreatic islets were seen in high fat fed rats,
      but no changes of skeletal muscles and livers were observed. mRNA levels of
      GLUT2, alpha-glucosidase in small intestinal epithelium and Kir6.2 mRNA in beta
      cells of islets increased, whereas that of GLUT4 in skeletal muscles decreased in
      high fat fed group compared with normal control group. CONCLUSION: An insulin
      resistance animal model in Wistar rats is established by ig special fat emulsion.

PMID- 15968720
TI  - Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver
      regeneration on acute hepatic injury and hepatic failure in rats.
AB  - AIM: To study the protective effect of eukaryotic expression plasmid encoding
      augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure
      in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid,
      and used to treat rats with acute hepatic injury. The rats with acute hepatic
      injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride
      (CCl(4)) were randomly divided into saline control group and recombinant pcDNA3
      ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200
      microg/kg) was injected into the rats with acute hepatic injury intravenously,
      intraperitoneally, or intravenously and intraperitoneally in combination 4 h
      after CCl(4) administration, respectively. The recombinant plasmid was injected
      once per 12 h into all treatment groups four times, and the rats were decapitated
      12 h after the last injection. Hepatic histopathological alterations were
      observed after HE staining, the expression of proliferating cell nuclear antigen
      (PCNA) in liver tissue was detected by immunohistochemical staining, and the
      level of serum aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) was determined by biochemical method. The recombinant plasmid DNA (200
      microg/kg) and saline were intraperitoneally injected into the rats with acute
      hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl(4) after
      4 h of CCl(4) administration, respectively. Rats living over 96 h were considered
      as survivals. RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid
      was accordant with the reported sequence of rat ALR cDNA. After the rats with
      acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree
      of liver histopathological injury markedly decreased. The pathologic liver
      tissues, in which hepatic degeneration and necrosis of a small amount of
      hepatocytes and a large amount of infiltrating inflammatory cells were observed,
      and they became basically normal in the most effective group after four times of
      injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly
      increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to
      model group. The level of serum AST and ALT remarkably reduced in recombinant
      pcDNA3-ALR plasmid treatment groups compared to model group. The results showed
      that the effect of 200 microg/kg recombinant pcDNA3-ALR plasmid in the rats with
      acute liver injury was stronger than that of 50 microg/kg pcDNA3-ALR DNA. The
      effect of intravenous injection of recombinant pcDNA3-ALR plasmid was better.
      After the rats with acute hepatic failure were treated with recombinant pcDNA3
      ALR plasmid, the survival rate (40%) significantly increased in treatment groups
      compared to control group (15%, P<0.01). CONCLUSION: The ALR gene may play an
      important role in relieving acute hepatic injury and hepatic failure by promoting
      hepatic cell proliferation and reducing level of AST and ALT in CCl(4)
      intoxicated rats.

PMID- 15968721
TI  - Kinase domain insert containing receptor promotor controlled suicide gene system
      kills human umbilical vein endothelial cells.
AB  - AIM: To evaluate the killing effect of double suicide gene mediated by adenovirus
      and regulated under kinase domain insert containing receptor (KDR) promoter on
      human umbilical vein endothelial cells. METHODS: By PCR technology, human KDR
      promoter gene, Escherichia coli (E. coli) cytosine deaminase (CD) gene and the
      herpes simple virus-thymidine kinase (TK) gene were cloned. Plasmid pKDR-CDglyTK
      was constructed with them. Then, a recombinant adenoviral plasmid pAdKDR-CDglyTK
      was constructed in a "two-step transformation protocol". The newly constructed
      plasmids were transfected to 293 packaging cells to grow adenoviruses, which were
      further propagated and purified. Human umbilical vein endothelial cells (HUVEC)
      were infected with a different multiplicity of infection (MOI) of resultant
      recombinant adenovirus, the infection rate was measured with the aid of (GFP)
      expression. Infected cells were cultured in culture media containing different
      concentrations of (GCV) and/or 5-(FC), and the killing effects were measured.
      RESULTS: Recombinant adenoviruses AdKDR-CDglyTK were successfully constructed,
      and they infected HUVEC cells efficiently. Our data indicated that the infection
      rate was relevant to MOI of recombinant adenoviruses. HUVEC cells infected with
      AdKDR-CDglyTK were highly sensitive to the prodrugs, their survival rate
      correlated to both the concentration of the prodrugs and the MOI of recombinant
      adenoviruses. Our data also indicated that the two prodrugs used in combination
      were much more effective on killing transgeneic cells than GCV or 5-FC used
      alone. CONCLUSION: Prodrug/KDR-CDglyTK system is effective on killing HUVEC
      cells, its killing effect correlates to the concentration of prodrugs and
      recombinant adenovirus' MOI. Combined use of the two prodrugs confers better
      killing effects on transgeneic cells.

PMID- 15968722
TI  - Diminution of toxic copper accumulation in toxic milk mice modeling Wilson
      disease by embryonic hepatocyte intrasplenic transplantation.
AB  - AIM: To observe the therapeutic effect of intrasplenic transplantation with
      embryonic hepatocytes on amelioration of hereditary copper accumulation in toxic
      milk (TX) mouse modeling Wilson disease. METHODS: Donor hepatocytes were
      harvested from 14-d fetal liver of a pregnant homogeneous DL mouse. These cells
      were successively cultured, labeled with fluorescein dye Hoechst 33342 for 24 h,
      and sequentially infused into the spleen parenchyma of the recipient TX mice. No
      host immunosuppression measures were taken. Two and four weeks after
      transplantation, the recipients were killed for routine histologic investigation
      and immunohistochemistry study up to 4 wk after transplantation. The serum copper
      and ceruloplasmin concentrations of the recipient mice were determined by
      graphite furnace atomic absorption spectroscopy. RESULTS: In the following 2nd
      and 4th wk after transplantation, the donor hepatocytes could be visualized in
      the livers of 47.3% recipients. The serum ceruloplasmin and copper concentrations
      increased by 1.6-fold after 2 wk and 2.0-fold times after 4 wk respectively,
      which ultimately rose from about 30% of the normal level to nearly 60% (P<0.01).
      The hepatic copper concentration decreased 7.2%, 4 wk after transplantation.
      Pathologic examination showed that there were many actively proliferative
      hepatocyte precursor cells with specific embryonic hepatocyte marker AFP migrated
      into hepatic sinusoids of the recipients. A large number of cells carrying
      hepatocytes marker and albumin were observed in the recipient spleen tissues.
      CONCLUSION: Embryonic hepatocytes are capable of differentiating into mature
      hepatocytes in vivo. After transplantation, the hereditary abnormalities of
      copper metabolism in TX mice could be corrected partially by intrasplenic
      transplantation of homogeneous embryonic hepatocytes.

PMID- 15968723
TI  - Expression of tissue inhibitor of matrix metalloproteinases-1 during aging in rat
      liver.
AB  - AIM: To investigate the expression and role of tissue inhibitor of matrix
      metalloproteinases-1 (TIMP-1) during natural aging in rat liver and to detect the
      expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. METHODS: The rats
      were divided into 3-mo-old group (n = 5), 10-mo-old group (n = 5) and 24-mo-old
      group (n = 5). Histopathologic changes of liver were observed with HE and Masson
      stain. The location and protein expressions of TIMP-1 were determined by
      immunohistochemistry and Western blot; message RNA (mRNA) levels were measured in
      livers from rats of various ages by semi-quantitative reverse transcriptional
      polymerase chain reaction (RT-PCR). In addition, the expression of MMP-2 and MMP
      9 was assessed by RT-PCR and Western blot. RESULTS: Histologic examination showed
      that the aging liver had excessive fatty degeneration and collagen deposition.
      Immunohistochemical staining showed that TIMP-1 related antigen in livers was
      located in cytoplasm. The protein expression of TIMP-1 was significantly higher
      in the oldest animals and the mRNA expression was increased significantly in the
      24-mo-old rats (t = 4.61, P = 0.002<0.05, 24-vs 10-mo-old rats; t = 4.31, P =
      0.003<0.05, 24- vs 3-mo-old rats). The expression of MMP-2 and MMP-9 had no
      change during aging; the ratios TIMP-1/MMP-2 and TIMP-1/MMP-9 in aging liver were
      significantly higher than those in maturation and young livers. CONCLUSION: TIMP
      1 may play an important role in the process of liver aging.

PMID- 15968724
TI  - Tumor necrosis factor-alpha induces apoptosis of enterocytes in mice with
      fulminant hepatic failure.
AB  - AIM: To explore the alterations of intestinal mucosa morphology, and the effects
      of tumor necrosis factor alpha (TNFalpha) on enterocyte apoptosis in mice with
      fulminant hepatic failure (FHF). METHODS: Liver damage was induced by
      lipopolysaccharide (LPS)/TNF-alpha in D-galactosamine (GalN) sensitized BALB/c
      mice. There were 40 mice in normal saline (NS)-treated group, 40 mice in LPS
      treated group, 40 mice in GalN-treated group, 120 mice in GalN/ LPS-treated group
      and 120 mice in GalN/TNFalpha-treated group. Each group was divided into five
      subgroups of eight mice each. Serum samples and liver, intestinal tissues were
      respectively obtained at 2, 6, 9, 12 and 24 h after administration. Anti-TNFalpha
      monoclonal antibody was injected intravenously into GalN/LPS-treated mice. Serum
      TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA).
      Serum ALT levels were determined using an automatic analyzer. The intestinal
      tissues were studied under light microscope and electron microscope at 2, 6, 9,
      12 and 24 h in mice with fulminant hepatic failure, respectively. Enterocyte
      apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end labeling (TUNEL) method. The expression of tumor necrosis factor
      receptor 1 (TNFR1) in intestinal tissue was tested by immunohistochemistry
      Envision Two Steps. RESULTS: Gut mucosa was morphologically normal at all time
      points in all groups, but typical apoptotic cells could be seen in all
      experimental groups under electron micro-scope. Apoptosis rate of gut mucosal
      epithelial cells were significantly increased at 6, 9 and 12 h, peaked at 12 h in
      mice with fulminant hepatic failure. TNFalpha induced apoptosis of enterocytes in
      mice with FHF. The integrated OD (IOD) levels of TNFalpha receptor 1 protein
      expressed in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF
      at 2, 6, 9, 12 and 24 h after GalN/LPS and GalN/TNFalpha administration were
      169.54+/-52.62/905.79+/-111.84, 11,350.67+/-2 ,133.26/28,160.37+/-4,601.67,
      25,781.00 +/-2,277.75/122,352.30+/-49,412.40, 5,241.53+/-3,007.24/49,157.93+/
      9,804.88, 7,086.13+/-1,031.15/3,283.45+/-127.67, respectively, compared with
      those in control groups (with NS, LPS and GalN administration, respectively). IOD
      level of TNFR1 changed significantly at 6, 9 and 12 h after GalN/LPS and
      GalN/TNFalpha administration. The expression of TNFR1 protein was significantly
      higher at 9 h after GalN/LPS and GalN/TNFalpha administration than that in
      control groups. Protein expression of TNFR1 was positively correlated with
      enterocyte apoptosis. CONCLUSION: TNFalpha can induce apoptosis of enterocytes in
      mice with FHF. Anti-TNFalpha IgG can inhibit this role.

PMID- 15968725
TI  - High expressions of caveolins on the proliferating bile ductules in primary
      biliary cirrhosis.
AB  - AIM: An increase in bile ductular structures is observed in diverse human liver
      diseases, especially in primary biliary cirrhosis (PBC). These structures harbor
      the progenitor cell component of the liver. Caveolins are cholesterol-binding
      proteins involved in the regulation of several intracellular processes including
      cholesterol transport. This study aims to examine the role of caveolin in PBC.
      METHODS: Immunohistochemical and Western blotting studies were performed on human
      liver specimens obtained from patients with PBC and normal liver samples. The
      expression of caveolin (CAV)-1 and -2 was determined using specific antibodies.
      RESULTS: In normal liver, scanty immunostaining for CAV-1 and -2 was observed in
      bile ductules. In PBC liver samples, the expression levels of CAV-1 and -2 were
      increased on proliferating bile ductules especially in stage 3 cases, but was
      sparse on interlobular bile duct in stage 1 specimens. Especially, the
      regenerating bile ductules at the interface of portal tracts and necrotic areas
      were immunostained intensely for CAV-1 and -2. These phenomena were confirmed by
      Western blot. CONCLUSION: The present results demonstrate increased expression of
      caveolins in proliferating bile ductules in PBC, which may be related to the
      homeostasis of cholesterol transport in regenerating bile ductules in PBC liver.

PMID- 15968726
TI  - Clinical application of clip-assisted endoscopic method for nasoenteric feeding
      in patients with gastroparesis and gastroesophageal wounds.
AB  - AIM: To report the clinical experiences in the application of clip-assisted
      endoscopic method for nasoenteric feeding in patients with gastroparesis and
      patients with gastroesophageal wounds, and to compare the efficacy of nasoenteric
      feeding in these two indications. METHODS: From April 2002 to January 2004, 21
      consecutive patients with gastroparesis or gastroesophageal wounds were enrolled
      and received nasoenteric feeding for nutritional support. A clip-assisted method
      was used to place the nasoenteric tubes. Outcomes in the two groups were compared
      with respect to the successful rate of enteral feeding, percentage of recommended
      energy intake (REI), and complication rates. RESULTS: The gastroparesis group
      included 13 patients with major burns (n = 7), trauma (n = 2), congestive heart
      failure (n = 2) and post-surgery gastric stasis syndrome (n = 2). The
      esophageogastric wound group included eight patients with tracheoesophageal
      fistula (n = 2) and wound leakage following gastric surgery (n = 6). Two study
      groups were similar in feeding successful rates (84.6% vs 75.0%). There were also
      no differences in the percentage of REI between groups (79.4% vs 78.6%).
      Additionally, no complications occurred in any of the study groups. CONCLUSION:
      Nasoenteric feeding is a useful method to provide nutritional support to most of
      the patients with gastroparesis who cannot tolerate nasogastric tube feeding and
      to the cases who need bypass feeding for esophageogastric wounds.

PMID- 15968727
TI  - Action and mechanism of Fas and Fas ligand in immune escape of gallbladder
      carcinoma.
AB  - AIM: To study the role of Fas and Fas ligand (FasL) in biological behaviors of
      gallbladder carcinoma, and their correlated action and mechanism in tumor escape.
      METHODS: Streptavidin-biotin-peroxidase immunohistochemistry technique was used
      to study the expression of Fas and FasL protein in 26 gallbladder carcinoma
      tissues, 18 gallbladder adenoma tissues, 3 gallbladder dysplasia tissues and 20
      chronic cholecystitis tissues. Apoptosis of the infiltrating lymphocytes in these
      tissues was studied by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP
      nick-end labeling (TUNEL) method. Expression of both proteins and apoptosis of
      the tumor infiltrating lymphocytes in cancer tissues of primary foci was compared
      with clinicopathological features of gallbladder carcinoma. RESULTS: The positive
      rates of Fas were not significantly different among carcinoma, adenoma, dysplasia
      and chronic cholecystitis. The positive rate of FasL in carcinoma was
      significantly higher than that in chronic cholecystitis (chi(2) = 4.89, P<0.05).
      The apoptotic index (AI) in carcinoma was significantly higher than that in
      adenoma (t' = 4.19, P<0.01) and chronic cholecystitis (t' = 8.06, P<0.01). The AI
      was significantly lower in well-differentiated carcinoma and Nevin I-III
      carcinoma than that in poorly-differentiated carcinoma (t' = 2.63, P<0.05) and
      Nevin IV-V carcinoma (t' = 3.33, P<0.01). The confidence interval (CI) of
      infiltrating lymphocytes in adenoma, chronic cholecystitis, well-differentiated
      carcinoma and Nevin I-III carcinoma was very significantly lower than that in
      carcinoma (t' = 6.99, P<0.01), adenoma (t' = 3.66, P<0.01), poorly-differentiated
      carcinoma (t' = 5.31, P<0.01) and Nevin IV-V carcinoma (t' = 3.76, P<0.01),
      respectively. The CI of apoptosis of infiltrating lymphocytes in well
      differentiated carcinoma was significantly lower than that in poorly
      differentiated carcinoma (t = 2.52, P<0.05), and was not significantly lower in
      Nevin I-III carcinoma than in Nevin IV-V carcinoma (t = 1.42, P>0.05). Apoptosis
      of infiltrating lymphocytes was not discovered in adenoma and chronic
      cholecystitis. CONCLUSION: FasL expressed in gallbladder carcinoma cells permits
      tumor cells to escape from immune surveillance of organism by inducing apoptosis
      in infiltrating lymphocytes of carcinoma tissues. Up-regulation of FasL
      expression plays an important role in invasive depth, histological classification
      and metastasis of gallbladder carcinoma.

PMID- 15968728
TI  - Cyclooxygenase-2 promotes angiogenesis by increasing vascular endothelial growth
      factor and predicts prognosis in gallbladder carcinoma.
AB  - AIM: To investigate the relationships between the expression of cyclooxygenase-2
      (COX-2), vascular endothelial growth factor (VEGF) and the degree of
      vascularization, clinicopathologic feature, survival time of patients with
      gallbladder carcinomas. METHODS: Sixty-four gallbladder carcinoma specimens were
      evaluated for COX-2, VEGF expression by immunohistochemical methods. Microvessel
      counts (MVC) were determined using CD(34). The relationships between COX-2, VEGF
      expression, CD(34)-stained MVC, clinicopathologic features and survival time were
      analyzed. The correlations between COX-2 and VEGF expression, CD(34)-stained MVC
      were also investigated. RESULTS: COX-2, VEGF immunoreactivity were observed in
      71.9% (46/64) and 54.7% (35/64) specimens, respectively. The average MVC in 64
      cases of gallbladder carcinoma was 57+/-14 per high power vision field. The
      status of MVC was closely correlated with Nevin staging, tumor differentiation
      and lymph node metastasis (P<0.01, 0.002, and 0.003, 0.000, respectively).
      Increased VEGF expression was significantly correlated with tumor differentiation
      (poorly and moderately>well differentiated, P<0.05, P = 0.016). Clinical stages
      had no relation with the expression of VEGF (P>0.05, P = 0.612). There was a
      positive correlation between COX-2 expression and clinical stages. The positive
      rate of COX-2 was higher in cases of Nevin stages S(4)-S(5) (81.8%) than in those
      of Nevin stages S(1)-S(3) (50.0%) with a statistical significance (P<0.01, P =
      0.009). The expression of COX-2 did not vary with differentiation (P>0.05, P =
      0.067). Statistically significant differences were also observed according to
      lymph node metastasis, COX-2 expression and VEGF expression (P<0.01, 0.000, and
      0.001, respectively). There was no relation between VEGF, COX-2 expression, MVC
      and the age and sex of patients. MVC and VEGF positive rate in the COX-2 positive
      gallbladder carcinoma tissue was higher than that in the COX-2 negative tissue
      (P<0.05, 0.000, and 0.032, respectively). Patients with VEGF, COX-2 positive
      tumors had a significantly shorter survival time than those with negative tumors
      (P<0.05, 0.004, 0.01, respectively). CONCLUSION: Augmented tumor
      neovascularization induced by VEGF may be one of the several effects of COX-2
      responsible for poor prognosis of human gallbladder carcinoma. COX-2 inhibitor,
      either in combination therapy with other agents, or for chemoprevention, may be
      effective via suppression of angiogenesis in this fatal disease.

PMID- 15968729
TI  - Hepatosplenic gammadelta T-cell lymphoma.
AB  - AIM: To investigate the clinicopathologic characteristics, immunophenotype and
      TCR gene rearrangements of hepatosplenic T-cell lymphoma in eight Chinese
      patients. METHODS: Eight Chinese patients with hepatosplenic gammadelta T-cell
      lymphomas were studied. Hematoxylin-eosin-stained slides and clinical histories
      were reviewed. We also carried out immunohistochemical staining for CD3, CD4,
      CD8, CD20, CD43, CD56, CD79a, UCHL-1, and TCR gammadelta. Rearrangements of TCR
      gamma and delta chain genes were also studied. RESULTS: The spleens were enlarged
      and the cut surfaces were homogeneous and red-purple in color without
      identifiable gross lesions or enlarged hilar lymph nodes. Histologically,
      lymphoma cells infiltrated the cords of Billroth and often packed the sinuses.
      Liver biopsy showed lymphoma cell infiltrations in the sinusoids, and three cases
      showed involvements of the portal tracts. Immunohistochemically lymphoma cells
      were positive for CD3, CD43, and CD56 in all cases. Four of eight cases were
      positive for CD8, and all cases were negative for CD4 (6/6). Monoclonal
      rearrangements of TCR gamma gene were demonstrated by PCR analysis in five out of
      the eight cases. TCR delta gene rearrangements were detected in six out of the
      eight cases, which demonstrated single bands on PAGE gel, and the amplification
      products in two cases were confirmed by sequencing. CONCLUSION: The
      clinicopathology of hepatosplenic gammadelta T-cell lymphoma in Chinese patients
      is similar to what was previously reported except that the splenomegaly is not so
      massive, and CD8 is positive.

PMID- 15968730
TI  - Multivariate analysis of the risk for pulmonary complication after
      gastrointestinal surgery.
AB  - AIM: To identify the risk factors for postoperative pulmonary complications (PPC)
      after gastrointestinal surgery. METHODS: A total of 1 002 patients undergoing
      gastrointestinal surgery in the Second Affiliated Hospital, Sun Yat-Sen
      University, during December 1999 and December 2003, were retrospectively studied.
      RESULTS: The overall incidence of PPC was 22.8% (228/1,002). Multivariate
      logistic analysis identified nine risk factors associated with PPC, including age
      odds ratio (OR = 1.040) history of respiratory diseases (OR = 2.976), serum
      albumin (OR = 0.954), chemotherapy 2 wk before operation (OR = 3.214), volume of
      preoperative erythrocyte transfusion (OR = 1.002), length of preoperative
      antibiotic therapy (OR=1.072), intraoperative intratracheal intubation (OR =
      1.002), nasogastric intubation (OR = 1.050) and postoperative mechanical
      ventilation (OR = 1.878). Logistic regression equation for predicting the risk of
      PPC was P(1) = 1/[1+e(-(-3.488+0.039 x Y+1.090 x Rd+0.001 x Rbc-0.047 x Alb+0.002
      x Lii+0.049 x Lni+0.630 x Lmv+0.070 x Dat+1.168 x Ct))]. CONCLUSION: Old patients
      are easier to develop PPC.

PMID- 15968731
TI  - Value of gastrografin in adhesive small bowel obstruction after unsuccessful
      conservative treatment: a prospective evaluation.
AB  - AIM: Gastrografin is a hyperosmolar water-soluble contrast medium. Besides its
      predictive value for the need for operative treatment, a potential therapeutic
      role of this agent in adhesive small bowel obstruction has been suggested. This
      study aimed at evaluating the effectiveness of gastrografin in adhesive small
      bowel obstruction when conservative treatment failed. METHODS: Patients with
      adhesive small bowel obstruction were given trial conservative treatment unless
      there was fear of bowel strangulation. Those responded in the initial 48 h had
      conservative treatment continued. Patients who showed no improvement in the
      initial 48 h were given 100 mL of gastrografin through nasogastric tube followed
      by serial abdominal radiographs. Patients with the contrast appeared in large
      bowel within 24 h were regarded as having partial obstruction and conservative
      treatment was continued. Patients in which the contrast failed to reach large
      bowel within 24 h were considered to have complete obstruction and laparotomy was
      performed. RESULTS: Two hundred and twelve patients with 245 episodes of adhesive
      obstruction were included. Fifteen patients were operated on soon after admission
      due to fear of strangulation. One hundred and eighty-six episodes of obstruction
      showed improvement in the initial 48 h and conservative treatment was continued.
      Two patients had subsequent operations because of persistent obstruction. Forty
      four episodes of obstruction showed no improvement within 48 h and gastrografin
      was administered. Seven patients underwent complete obstruction surgery. Partial
      obstruction was demonstrated in 37 other cases, obstruction resolved subsequently
      in all of them except one patient who required laparotomy because of persistent
      obstruction. The overall operative rate in this study was 10%. There was no
      complication that could be attributed to the use of gastrografin. CONCLUSION: The
      use of gastrografin in adhesive small bowel obstruction after unsuccessful
      conservative treatment is safe and reduces the need for surgical intervention.

PMID- 15968732
TI  - Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer
      in rats.
AB  - AIM: To evaluate the preventive effect of Ginkgo biloba extract (GbE) on ethanol
      induced gastric mucosal injuries in rats. METHODS: Female Wistar albino rats were
      used for the studies. We randomly divided the rats for each study into five
      subgroups: normal control, experimental control, and three experimental groups.
      The gastric ulcers were induced by instilling 1 mL 50% ethanol into the stomach.
      We gave GbE 8.75, 17.5, 26.25 mg/kg intravenously to the experimental groups
      respectively 30 min prior to the ulcerative challenge. We removed the stomachs 45
      min later. The gastric ulcers, gastric mucus and the content of non-protein
      sulfhydryl groups (NP-SH), malondialdehyde (MDA), c-Jun kinase (JNK) activity in
      gastric mucosa were evaluated. The amount of gastric juice and its acidity were
      also measured. RESULTS: The findings of our study are as follows: (1) GbE
      pretreatment was found to provide a dose-dependent protection against the ethanol
      induced gastric ulcers in rats; (2) the GbE pretreatment afforded a dose
      dependent inhibition of ethanol-induced depletion of stomach wall mucus, NP-SH
      contents and increase in the lipid peroxidation (increase MDA) in gastric tissue;
      (3) gastric ulcer induced by ethanol produced an increase in JNK activity in
      gastric mucosa which also significantly inhibited by pretreatment with GbE; and
      (4) GbE alone had no inhibitory effect on gastric secretion in pylorus-ligated
      rats. CONCLUSION: The finding of this study showed that GbE significantly
      inhibited the ethanol-induced gastric lesions in rats. We suggest that the
      preventive effect of GbE may be mediated through: (1) inhibition of lipid
      peroxidation; (2) preservation of gastric mucus and NP-SH; and (3) blockade of
      cell apoptosis.

PMID- 15968733
TI  - Relation of CagA seropositivity to cagPAI phenotype and histological grade of
      gastritis in patients with Helicobacter pylori infection.
AB  - AIM: Infection with Helicobacter pylori (H pylori) possessing the cag
      pathogenicity island (PAI) has been associated with severe clinical outcome and
      CagA-antibody has been used to indicate cagPAI-positive infection. The aim of
      this study was to examine the accuracy of CagA seropositivity to indicate the
      virulence of the cagPAI in Japan. METHODS: Sixty isolates of H pylori cultured
      from gastric biopsies were examined by polymerase chain reaction assays for the
      presence of cagA, cagE and VirD4. Anti-CagA IgG antibody in matching sera was
      tested by both ELISA and immunoblot assay. Histological grade of gastritis was
      graded according to the updated Sydney System. RESULTS: Amongst 53 patients
      infected with cagA+/cagE+/VirD4+ strain, 38 were CagA seropositive. There were
      four patients infected with strains possessing incomplete cagPAI. Two out of
      three patients with cagA+/cagE-/VirD4- infection were CagA seropositive, while a
      patient with cagA-/cagE+/VirD4+ infection was CagA seronegative. Accuracy of
      ELISA to predict bacterial possession of cagA was 61.7% whereas 58.3% for cagE
      and VirD4. The immunoblot assay showed relatively higher sensitivity and showed
      better accuracy. The lower grade of gastric mucosal inflammatory infiltration was
      seen in false CagA-seronegative patients. CONCLUSION: Some serodiagnosis does not
      seem to have enough accuracy to indicate virulence of cagPAI, particularly in
      infection of strains with incomplete cagPAI. The degree of gastric mucosal
      inflammation may affect the results of CagA serodiagnosis.

PMID- 15968734
TI  - Preoperative evaluation of pancreaticobiliary tumor using MR multi-imaging
      techniques.
AB  - AIM: To evaluate the clinical value of MR multi-imaging techniques in diagnosing
      and preoperative assessment of pancreaticobiliary tumor. METHODS: MR multi
      imaging techniques, including MR cross-sectional imaging, MR
      cholangiopancreatography (MRCP) and 3D dynamic contrast-enhanced MR angiography
      (3D DCE MRA), were performed to make prospective diagnosis and preoperative
      evaluation in 28 patients with suspected pancreaticobiliary tumors. There were 17
      cases of pancreatic adenocarcinoma, 8 cases of biliary system carcinoma and 3
      cases of non-neoplastic lesions. RESULTS: Using MR multi-imaging techniques, the
      accuracy in diagnosing the patients with pancreaticobiliary tumors was 89.3%
      (25/28). The accuracy in detecting the range of tumor invasion was 80.3% (57/71).
      The sensitivity, specificity, accuracy, positive and negative predictive value of
      MR multi-imaging techniques in preoperative assessment of the resectability of
      pancreaticobiliary tumor were 83.3%, 89.5%, 88.0%, 71.4%, and 94.4%,
      respectively. There was well diagnostic consistency between MR multi-imaging
      techniques and CT (kappa = 0.64, P<0.01). The fusion image could be made from
      MRCP and 3D DCE MRA images. CONCLUSION: MR multi-imaging techniques can integrate
      the advantages of various MR images. The non-invasive "all-in-one" MR imaging
      protocol is the efficient method in diagnosing, staging and preoperative
      assessment of pancreaticobiliary tumor.

PMID- 15968735
TI  - Comparison of six human anti-transglutaminase ELISA-tests in the diagnosis of
      celiac disease in the Saharawi population.
AB  - AIM: Celiac disease (CD) is an enteropathic disorder very prevalent in Saharawi
      people. Our aim was to investigate the diagnostic accuracy of six human tissue
      transglutaminase (tTG) based ELISA tests in Saharawi CD patients. METHODS: Fifty
      two CD patients and 23 controls were selected from the Saharawi refugee camps in
      Tinduf. CD patients were divided into two groups according to their anti
      endomysium (EmA) status: 41 EmA positive and 11 EmA negative. Sera from patients
      and controls were tested for human tTG using six commercial ELISA kits. We used
      receiver operating characteristics (ROC) curves and areas under the curve to
      compare the diagnostic accuracies of the six assays. RESULTS: In general, there
      are differences in the sensitivity and specificity of the human tTG ELISA assays
      used. Diagnostic accuracy of tests was significantly improved by adjusting the
      cut-off thresholds according to ROC plot analysis; the correction of the cut-off
      with the employment of the ROC curve analysis modifies the decision limit in more
      than 50% in five of the six kits evaluated. CONCLUSION: Some of the human tTG
      ELISAs used in this study have a diagnostic accuracy similar to EmA determination
      for diagnosis of CD in Saharawi people. However, it is necessary to select the
      assay with a higher sensitivity and specificity, and recalculate the cut-off
      threshold using samples from the referral population.

PMID- 15968736
TI  - Expression of macrophage migration inhibitory factor is associated with enhanced
      angiogenesis and advanced stage in gastric carcinomas.
AB  - AIM: Macrophage migration inhibitory factor (MIF) was reported to inactivate p53
      and play an essential role in the growth and angiogenesis of tumors that arise at
      sites of chronic inflammation. Gastric inflammation is a prerequisite for the
      development of gastric carcinoma (GC), which has recently been linked to
      Helicobacter pylori (H pylori) infection. This study aimed to investigate
      clinicopathological significance of MIF expression in GCs. METHODS: We selected
      90 consecutive patients with GCs for investigation of the relation among MIF
      status, clinicopathological parameters, p53 expression and angiogenesis. MIF and
      p53 expression was assessed by immunohistochemistry as positive and negative
      groups. Tumor vascularity was evaluated by counting microvessel density on anti
      CD34 stained sections. Expression status of MIF was correlated with determined
      clinicopathological data, p53 immunoreactivity and microvessel counts. RESULTS:
      Strong immunostainings of MIF were observed in the cytoplasm of cancerous cells
      in 40% (36/90) of cases but not in normal or metaplastic epithelia. There was no
      statistically significant correlation between MIF expression and age, gender, H
      pylori infection, tumor location, histological subtypes, lymph node metastasis or
      p53 expression. Early GC less frequently overexpressed MIF as compared to
      advanced GCs (4/20 vs 32/70, P = 0.04). A remarkably increased microvessel count
      was noted in GCs with MIF expression than those without MIF expression (55.1+/
      30.1 vs 31.3+/-28.8, P = 0.0001). CONCLUSION: Our results suggest that expression
      of MIF may contribute to the progression and enhanced angiogenesis in a
      substantial portion of GCs.

PMID- 15968737
TI  - Depletion of CD25+CD4+T cells (Tregs) enhances the HBV-specific CD8+ T cell
      response primed by DNA immunization.
AB  - AIM: Persistent hepatitis B virus (HBV) infection is characterized by a weak
      CD8(+) T cell response to HBV. Immunotherapeutic strategies that overcome
      tolerance and boost these suboptimal responses may facilitate viral clearance in
      chronically infected individuals. Therefore, we examined whether CD25(+)CD4(+)
      regulatory T (Treg) cells might be involved in a inhibition of CD8(+) T cell
      priming or in the modulation of the magnitude of the 'peak' antiviral CD8(+) T
      cell response primed by DNA immunization. METHODS: B10.D2 mice were immunized
      once with plasmid pCMV-S. Mice received 500 microg of anti-CD25 mAb injected
      intraperitoneally 3 d before DNA immunization to deplete CD25(+) cells. Induction
      of HBV-specific CD8(+) T cells in peripheral blood mononuclear cells (PBMCs) was
      measured by S28-39 peptide loaded DimerX staining and their function was analyzed
      by intracellular IFN-gamma staining. RESULTS: DNA immunization induced HBV
      specific CD8(+) T cells. At the peak T cell response (d 10), 7.1+/-2.0% of CD8(+)
      T cells were HBV-specific after DNA immunization, whereas 12.7+/-3.2% of CD8(+) T
      cells were HBV-specific in Treg-depleted mice, suggesting that DNA immunization
      induced more antigen-specific CD8(+) T cells in the absence of CD25(+) Treg cells
      (n = 6, P<0.05). Similarly, fewer HBV-specific memory T cells were detected in
      the presence of these cells (1.3+/-0.4%) in comparison to Treg-depleted mice
      (2.6+/-0.9%) on d 30 after DNA immunization (n = 6, P<0.01). Both IFN-gamma
      production and the avidity of the HBV-specific CD8(+) T cell response to antigen
      were higher in HBV-specific CD8(+) T cells induced in the absence of Treg cells.
      CONCLUSION: CD25(+) Treg cells suppress priming and/or expansion of antigen
      specific CD8(+) T cells during DNA immunization and the peak CD8(+) T cell
      response is enhanced by depleting this cell population. Furthermore, Treg cells
      appear to be involved in the contraction phase of the CD8(+) T cell response and
      may affect the quality of memory T cell pools. The elimination of Treg cells or
      their inhibition may be important in immunotherapeutic strategies to control HBV
      infection by inducing virus-specific cytotoxic T lymphocyte responses in
      chronically infected subjects.

PMID- 15968738
TI  - Dynamic change of epidermal growth factor in neonatal rat with intestine injury.
AB  - AIM: To determine whether diminished levels of epidermal growth factor (EGF) were
      present in neo-natal rats with intestinal injury and related with the degree of
      intestinal injury, so we modeled a model in neo-natal rats of intestinal injury
      and to examine the dynamic levels of EGF on injury of intestine. METHODS: One-day
      old Wistar rat pups received an intraperitoneally injection with 4 mg/kg
      lipopolysaccharide (LPS), followed by collection of ileum tissue at 1, 3, 6, 12,
      and 24 h following LPS administration. The ileum was for histological evaluation
      of NEC and for measurements of EGF using ABC-ELISA. The correlation between the
      degree of intestinal injury and levels of EGF was determined. RESULTS: The LPS
      injected pups also showed a significant increase in injury scores at 1, 3, 6, 12,
      and 24 h (respectively, (1.08+/-0.61), (1.63+/-0.84), (1.95+/-0.72), (2.42+/
      0.43) and (2.21+/-0.53)) vs the control (0.12+/-0.17) (P<0.01). EGF levels at 1,
      3, 6, 12 h (respectively, (245.6+/-49.0), (221.4+/-39.0), (223.4+/-48.1),
      (246.0+/-46.6)) pg/mg were significantly loss than the control (275.6+/-50.4)
      pg/mg (P<0.05). There was a significant negative correlation between the EGF
      levels and the grade of intestinal injury within 24 h (P<0.05). CONCLUSION: Neo
      natal rats with intestinal injury have significantly lower levels of ileum EGF.
      Reduced levels of this growth factor might be related to the pathogenesis of NEC.

PMID- 15968740
TI  - Ischemic enterocolitis examined by colonoscopy and selective angiography.
AB  - AIM: To study the value of colonoscopy and selective angiography in diagnosing
      ischemic enterocolitis. METHODS: Among the 16 cases under study, 10 cases had
      hypertension and a history of coronary artery disease (one was hospitalized for
      sub-ventricular-wall infarction). The blood pressure of 10 of the 16 cases ranged
      from 13.9-23.8 to 13.3-14.6 kPa (170-180/100-110 mmHg). Two cases had chronic
      auricular fibrillation, and in four cases, a cardiogram showed left-front branch
      conduction block. Sixteen patients were examined by colonoscopy. Among them, 14
      cases had a long course of angiocardiac disease, and were further examined by
      selective mesenteric inferior angiography. RESULTS: The colonoscopy revealed
      local mucous hyperemia edema and blood on contact. Lesions were found in the
      sigmoid colon in four cases, in the descending colon in eight cases and in
      splenic flexure in four cases, which suggests that the lesion always appeared in
      the left part of colon. There were different degrees of inflammatory cell
      infiltration, submucous bleeding, edema, fibro-embolism and hemosiderosis by
      biopsy in the 16 patients whose membranes affect part of the enteral wall. Of the
      14 patients examined by mesenteric inferior angiography, 3 cases showed
      mesenteric amphraxis inferior and formation of collateral circulation. There were
      different degrees of stenosis in the other 11 subjects' mesenteric inferior
      cavities which grew slim and their branches were stenotic, so the radiographic
      image was not complete and the ends of some branches even cannot be seen.
      CONCLUSION: The colonoscopy and the selective mesenteric inferior angiography are
      both helpful in the diagnosis of ischemic enterocolitis.

PMID- 15968739
TI  - Treatment for liver metastases from breast cancer: results and prognostic
      factors.
AB  - AIM: Liver metastases from breast cancer (BCLM) are associated with poor
      prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a
      decrease in symptoms. Available data, in the literature, also suggest a subgroup
      of patients may benefit from surgery, but few talked about transcatheter arterial
      chemoembolization (TACE). We report the results of TACE and systemic chemotherapy
      for patients with liver metastases from breast cancer and evaluate the prognostic
      factors. METHODS: Forty-eight patients with liver metastases, from proved breast
      primary cancer were treated with TACE or systemic chemotherapy between January
      1995 and December 2000. Treatment results were assessed according to WHO
      criteria, along with analysis of prognostic factors for survival using Cox
      regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response
      rates were calculated for the TACE group and chemotherapy group, being 35.7% and
      7.1%, respectively. The difference was significant. The one-, two- and three-year
      Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for
      the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to
      univariate analysis, variables significantly associated with survival were the
      lymph node status of the primary cancer, the clinical stage of liver metastases,
      the Child-Pugh grade, loss of weight. Other factors such as age, the intervals
      between the primary to the metastases, the maximal diameter of the liver
      metastases, the number of liver metastases, extrahepatic metastasis showed no
      prognostic significances. These factors mentioned above such as the lymph node
      status of the primary cancer, the clinical stage of liver metastases, the Child
      Pugh grade, loss of weight were also independent factors in multivariate
      analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may
      prolong survival in certain patients. This approach offers new promise for the
      curative treatment of the patients with metastatic breast cancer.

PMID- 15968741
TI  - Prolonged acute hepatitis A mimicking autoimmune hepatitis.
AB  - AIM: We report a case with a prolonged course of hepatitis A, with alanine
      aminotransferase (ALT) higher than 500 IU/L for more than 2 mo. METHODS: A middle
      aged woman had an elevated IgG level of more than 2,000 mg/dL, positive anti
      nuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA), but no
      evidence of persistent hepatitis A virus (HAV) infection. Liver biopsy findings
      were compatible with prolonged acute hepatitis, although acute onset of
      autoimmune hepatitis could not be ruled out. RESULTS: It was assumed that she
      developed a course of hepatitis similar to autoimmune hepatitis triggered by HAV
      infection. Ursodeoxycholic acid (UDCA) treatment was initiated and a favorable
      outcome was obtained. CONCLUSION: We describe a case of a middle-aged woman who
      showed a prolonged course of acute hepatitis A mimicking autoimmune hepatitis.
      Treatment with UDCA proved to be effective.

PMID- 15968742
TI  - Carcinoid tumor of the duodenum and accessory papilla associated with
      polycythemia vera.
AB  - Carcinoid tumors have been reported in a wide range of organs but most frequently
      involve the gastrointestinal tract; however, duodenal carcinoid tumors are rare.
      We report a 50-year-old male patient complaining of multiple melenas for 3 wk.
      The panendoscopy and endoscopic retrograde cholangiopancreaticography revealed
      swelling accessory papilla with an ulcer. The biopsy taken showed a carcinoid
      tumor. The lesion was removed by wide resection. Patient was found to have an
      abnormal blood cell count during the follow-up period with elevated levels of
      hemoglobin and hematocrit of 21.2 g/dL and 63.5%, respectively, thrombocytosis of
      501,000/microL, and leukocytosis of 20,410/microL. He was diagnosed as a
      polycythemia vera by a hematologist after further evaluation. He received
      periodic phlebotomy and hydroxyurea treatment. The response was good and his
      hematocrit was stabilized by periodic phlebotomy in the range of 44-49% during
      the last 2 years. The possible origin of UGI bleeding by a duodenal carcinoid
      tumor, although rare, should be considered. There has been one case report of a
      duodenal carcinoid tumor that involved accessory papilla of the pancreas divisum
      and one case report of metastatic carcinoid tumor associated with polycythemia
      vera. It is different in our patient as compared with the latter report, which
      mentioned a polycythemia vera patient who was found to have a metastatic
      carcinoid in the 17 years follow-up period. Chemotherapy had been given before
      the carcinoid tumor was revealed. Our patient had no previous chemotherapy for
      polycythemia vera before he was found to have duodenal carcinoid tumor; this
      excludes the possibility of chemotherapy induced carcinoid tumor, although it had
      been suspected in the previous report. In our patient, the existence of both
      diseases may be by predisposition of each other since both diseases have an
      increased incidence of other neoplasm, or they may be coexistent incidentally.

PMID- 15968743
TI  - Budd-Chiari syndrome: a case with a combination of hepatic vein and superior vena
      cava occlusion.
AB  - We here report a recent, rare case of Budd-Chiari syndrome, associated with a
      combination of hepatic vein and superior vena cava occlusion. A young female, who
      had been in good health, was admitted to our hospital because of massive ascites.
      The patient had used no oral contraceptives. Tests for coagulation disorders,
      hematological disorders, and antiphospholipid syndrome were all negative. Budd
      Chiari syndrome was diagnosed by radiographic examination. The patient was
      suffering from a combination of hepatic vein and superior vena cava occlusion. In
      particular, the venous flow returned from the liver mainly through a right
      accessory hepatic vein, and stenosis was recognized at the orifice of this
      collateral vein into the vena cava. Subsequently, the patient underwent
      percutaneous balloon dilatation therapy for this stenosis. After this treatment,
      the massive ascites was gradually reduced, and she was discharged from our
      hospital. It has now been one year since discharge, and the patient has been
      doing well. If deteriorating liver function or intractable ascites occur again, a
      liver transplantation may be anticipated. This is the first case report of Budd
      Chiari syndrome associated with a superior vena cava occlusion.

PMID- 15968744
TI  - Utility of fusion CT-PET in the diagnosis of small pancreatic carcinoma.
AB  - Pancreatic carcinoma has a poor prognosis and early detection is essential for
      potentially curative resection. Despite the wide array of diagnostic tools,
      preoperative detection of small pancreatic carcinomas remains difficult. We
      report a case of small pancreatic carcinoma of the head of pancreas with
      indeterminate findings on US, ERCP, MRI and EUS which was successfully diagnosed
      via fusion CT-PET. This case illustrates the utility of CT-PET in the diagnosis
      of patients with small pancreatic carcinoma with equivocal findings on
      conventional diagnostic modalities.

PMID- 15968745
TI  - Successful management of postoperative recurrence of hepatocellular carcinoma
      with p53 gene therapy combining transcatheter arterial chemoembolization.
AB  - Transcatheter arterial chemoembolization (TACE) has become the standard treatment
      for unresectable hepatocellular carcinoma (HCC). But this method has some
      shortages. p53 gene, which was found to be mutant in many human tumors, has been
      proved with broad-spectrum anti-tumor effects. We reported a 23-year-old patient
      with recurrent HCC after irregular hepatectomy. The p53 gene was applied to this
      patient. We injected percutaneously and infused transcatheterally p53 gene
      (Gendicine, Shenzhen Sibiono Bentech, China) into his recurrent nodules in liver
      respectively and 4 d later, the patient received TACE therapy. In the 2 mo follow
      up, the patient was in good clinical condition with normal liver function and no
      recurrence was identified. The case report proposed that recurrent HCC could be
      successfully treated with p53 gene therapy combining TACE.

PMID- 15968746
TI  - Intestinal failure in obstructive jaundice.

PMID- 15968747
TI  - Nonalcoholic fatty liver disease in developing countries.

PMID- 15968748
TI  - A glimmer of hope for Africa?

PMID- 15968749
TI  - Helping the informed patient decide.

PMID- 15968750
TI  - Debating drug use openly.

PMID- 15968751
TI  - [Clinical practice guidelines...again. Why?].

PMID- 15968752
TI  - [The follow-up of the asthmatic patient: high stakes for practice and
      evaluation].

PMID- 15968753
TI  - [Gas exchanges and COPD: on the interest of structure-function relationships].

PMID- 15968754
TI  - [The upper airway syndrome: clinical relevance and pathophysiology].

PMID- 15968755
TI  - [Compliance, therapeutic observance and therapeutic adherence: what do we speak
      about?].

PMID- 15968756
TI  - [The therapeutic impact of PET-FDG scanning in broncho-pulmonary cancer].
AB  - BACKGROUND: Because of the expected high performances of scintigraphic scans with
      [18F]-fluorodeoxyglucose (FDG) not only in diagnostics and but also in
      therapeutic impact, especially in thoracic oncology, there are a lot of French
      nuclear medicine departments which will soon be equipped with a positron emission
      tomograph (PET). MATERIAL AND METHODS: The Nuclear Medicine Department of the
      Hopital d'Instructions des Armees du Val-de-Grace, Paris, led a retrospective
      study among physicians interested in 338 FDG-PET exams performed between may 2000
      and march 2002 in order to compare its own results with international literature
      concerning four indications for lung cancer: pulmonary nodule or mass malignancy
      diagnostic, lung carcinoma extension evaluation, therapeutic efficiency,
      recurrence suspicion. RESULTS: There seems to be no divergence, regarding
      limitation induced by the not exhaustive analysis of the retrospective study:
      more than every two FDG-PET exam highly influenced the effective therapy.
      CONCLUSION: That is why clinical FDG-PET has to be widely developed to
      investigate lung cancer.

PMID- 15968757
TI  - [Tuberculosis control in France--evaluation of practice by a working group of the
      Societe de Pneumologie de Langue Francaise].
AB  - INTRODUCTION: The management of tuberculosis has been the subject of renewed
      interest in France. Recently, the recommendations and the regulations concerning
      the disease have been updated. However, the resources that are actually available
      and the processes in place in different French departments are not clearly known.
      A national survey was thus carried out by a working group of the SPLF in charge
      of the recommendations concerning the medical, social and administrative
      management of the disease. METHODS: A questionnaire was sent to the 100 French
      departmental Antituberculous Services (SLAT). This explored the structures,
      activity, organisation involved, and difficulties encountered in Tuberculosis
      management. RESULTS: Ninety SLAT took part in the study. Their answers reveal: a
      discordance between a number of cases notified to the Department of Sanitation
      and Health (DDASS) and the number of cases known to the SLAT; a disparity between
      means involved in this study and the number of patients followed up as well as
      the choice of populations targeted for tracing); a willingness to deal with
      contact tracing although the investigations around individual cases and the
      definition of which subjects should be followed up were variable; a demand for
      protocols, networks and national recommendations. CONCLUSIONS: The SLAT are
      involved in the fight against tuberculosis with 20 years experience. The needs
      expressed in this survey point the way towards future prioritary actions to
      improve tuberculosis control nationally.

PMID- 15968758
TI  - [Therapeutic education of COPD patients: what does the general practitioner say?
      Results of an automatic speech study analysis].
AB  - INTRODUCTION: Education in COPD is clearly recommended. The general practitioner
      (GP) plays a key role in COPD management, and his view on education in medicine
      is crucial for him to implement it. This work aims at exploring what is the GP's
      representation of education in COPD. METHODS: Twenty-seven GP were enrolled in
      this qualitative research focused on three points: "COPD patient", "COPD
      patient's education", "tools in COPD patient education". The interviews
      processing has been carried out by an ALCESTE software (Analysis of Co-occurrent
      Lexemes in the Simple Terms of a Text) that extracts the key significant
      structures of a text. RESULTS: Actually, the GPs do not really speak about
      therapeutic education, they have a rather fuzzy representation of it. They face,
      in their daily practice, a lack of patients' awareness of the disease, they call
      to mind an educational model group close to the Alcoholics Anonymous (AA), and
      the most adequate location for this education looks to be, for them, the
      hospital. The emotional dimension is noticed, targeted atthe patient and his
      family circle. In their relationship with their patients, the GPs describe their
      part as more prescriptive than educative. CONCLUSION: The GPs' speech analysis
      shows that education is not a part of their COPD management; the results of our
      study enable us to foresee the actions to carry out to develop the concept of
      COPD education in general practice.

PMID- 15968759
TI  - [Measurement of daily physical activity in patients with cystic fibrosis].
AB  - BACKGROUND: Cystic fibrosis (CF) patients often have a good level of daily
      activity contrasting with the impairment of pulmonary functions. The aim of this
      prospective study was to measure physical daily activity (PDA) in CF-patients and
      compare it with rest pulmonary functions and exercise tolerance. MATERIAL AND
      METHODS: Fifteen CF-patients and 9 control subjects have been recruted. PDA was
      measured during 7 days using an accelerometer: Global-PDA (daily mean counts per
      day), percentage of inactivity (1 to 2 METS), light activity (2 to 3 METS), and
      moderate-to-hard activity (greater than 3 METS). Spirometry (FEV1, Vital
      Capacity) and clinical exercice testing (VO2, workload) were also performed.
      RESULTS: Global-PDA of CF-patients was lower than control subjects (p < 0.05).
      Light activity (15.5 +/- 3.3% vs 13.4 +/- 2.4%) and inactivity (81.2 +/- 9% vs
      79.9 +/- 3.1%) were similar in both groups. Only moderate-to-hard activity was
      greater in control subjects than in CF-patients (6.7 +/- 1.6% vs 3.3 +/- 3.4%; p
      < 0.05). There were correlations between Global-PDA and moderate-to-hard activity
      (r = 0.94), FEV1 (r = 0.72), Vital Capacity (r = 0.77), workload peak (r = 0.88),
      and VO2peak (r = 0.70). CONCLUSION: CF-patients have a lower PDA than control
      subjects because of a lower moderate-to-hard activity (>3 METS). In clinical
      practice, interviewing a CF-patient on his "run-life" PDA (<3 METS) has poor
      relationship with his real "moderate-to-hard activity", and this is a confusing
      factor for clinicians.

PMID- 15968760
TI  - [Diagnosis and management of pleural effusions in critically iII patients].
AB  - INTRODUCTION: Pleural effusions are common in ICU patients. Causes include
      massive fluid resuscitation in shock, pneumonia--either community acquired or
      nosocomial, cardiac insufficiency, hypoalbuminemia and hepatic impairment.
      Pleural effusions frequently complicate cardiac and abdominal surgery and
      haemothorax may complicate trauma. STATE OF THE ART: The incidence of pleural
      effusions in the intensive care unit (ICU) varies depending on the screening
      method used, from about 8% for physical examination to more than 60% for routine
      ultrasonography. In the absence of clinical parameters to exclude infection
      pleurocentesis remains an essential aspect of management and is not
      contraindicated mechanical ventilation. This review of the diagnosis and
      management of pleural effusions in ICU patients reports the most recent data from
      the literature. Pleurocentesis can be performed safely in the ICU, even in
      mechanically ventilated patients. The absence of reliable clinical or laboratory
      test criteria for determining the cause of pleural effusions and the potentially
      devastating consequences of failing to diagnose and treat pleural infection are
      strong reasons to perform pleurocentesis in patients with clinically detectable
      pleural effusions and no contraindication to the procedure. PERSPECTIVES:
      Although the data reviewed indicate that the diagnosis and treatment of pleural
      effusions should follow the same rules in the ICU as they do elsewhere, several
      incompletely resolved issues deserve further investigation. These are summarised
      in an agenda for future research.

PMID- 15968761
TI  - [Markers of environmental tobacco smoke (ETS) exposure].
AB  - INTRODUCTION: Tobacco smoke is one of the most common air pollutants found in the
      indoor environment. Passive smoking is defined as the involuntary inhalation of
      tobacco smoke present in the air. This article examines the advantages and
      limitations of the methods that are available to measure environmental tobacco
      smoke exposure. STATE OF THE ART: Passive smoking can be assessed either by
      measuring tobacco smoke pollutants found in the air directly or by using
      biomarker assays, an indirect measure of exposure. CONCLUSION: As far as the
      direct measurement of air pollutants is concerned, nicotine and 3-Ethenylpyridine
      levels seem most suitable because of their specificity. Four specific biological
      markers of tobacco smoke exposure are available: nicotine, cotinine,
      thiocyanates, and protein or DNA adducts. Only urinary cotinine assay can be
      retained as a reliable marker of exposure to tobacco smoke. It has been used as a
      reference in most epidemiological studies but only reflects tobacco exposure over
      the preceding 48 hours. The measurement of nicotine and cotinine levels in the
      appendages of the skin (hair and nails) reflects exposure to tobacco over the
      previous three months and could become a better reference marker in
      epidemiological and toxicological studies.

PMID- 15968762
TI  - [Manual abdominal compression for the detection of expiratory flow limitation].
AB  - INTRODUCTION: Expiratory flow limitation (EFL) is a characteristic feature of
      chronic obstructive pulmonary disease (COPD) and leads to dynamic hyperinflation
      (DH) which is a major source of dyspnoea, particularly during exercise. STATE OF
      THE ART: A new technique for the detection of EFL, based on manual compression of
      the abdomen (MCA), was assessed both in normal subjects and patients with COPD.
      MCA was always associated with a moderate increase in pleural pressure and
      allowed the detection of EFL in a reproducible manner, in both the seated and
      supine postures. The technique was well tolerated. It was also a reliable method
      for the detection of EFL during exercise since EFL detection was effectively
      associated with the development of DH. Finally, MCA was also compared to NEP in
      patients with obstructive sleep apnoea syndrome (OSAS) and in these patients, MCA
      invariably increased expiratory flow whereas the NEP method produced flow
      limitation in some cases because of upper airway collapse. PERSPECTIVES: EFL
      detection with MCA may be clinically useful since EFL is a determinant of
      dyspnoea, affects ventilatory response to exercise as well as maximum exercise
      capacity. CONCLUSIONS: MCA is a reliable technique for the detection of EFL in
      different positions, during resting breathing or exercise, requiring neither
      special equipment nor patient cooperation.

PMID- 15968763
TI  - [Persistent air leak (PAL): conservative vs. invasive approach?].
AB  - INTRODUCTION: An air leak following pulmonary resection is generally defined as
      persistent, or prolonged, if it fails to resolve within the first post-operative
      week. The precise definition has varied from study to study. STATE OF ART:
      Persistent air leak represents the most frequent complication in patients
      undergoing general thoracic procedures. The groups most at risk are elderly
      patients, patients with chronic obstructive pulmonary disease (COPD), and those
      who have general risk factors such as diabetes mellitus or who are taking oral
      steroids. The surgical procedures most commonly affected are upper lobectomies
      and lung volume reduction surgery for end-stage emphysema. PERSPECTIVES:
      Technically, performing a pleural tent at the time of an upper lobectomy may
      decrease the incidence of prolonged air leak. Reinforcement or buttressing of the
      staple line has been shown to decrease both the incidence and the duration of air
      leaks, but this increases costs and should thus be reserved for patients with
      lung parenchyma at the highest risk. The use of biological glues can be helpful
      in reducing the duration of chest tube drainage when applied intraoperatively for
      moderate and/or severe parenchymal air leaks, however, their systematic use in
      not recommended. The management of chest tube drainage after pulmonary resection
      varies widely from one institution to another. Most recent reports have favoured
      early discontinuation of negative pressure drainage and a move to underwater seal
      drainage (from the second post-operative day), however, no large scale randomised
      study is yet available to compare this with a more conservative approach.
      CONCLUSIONS: The management of persistent air leak following surgery requires
      identification of risk factors, good surgical technique and appropriate chest
      tube management.

PMID- 15968764
TI  - [Alveolar hypoventilation during sleep and domiciliary assisted ventilation].
AB  - INTRODUCTION: An alveolar hypoventilation physiologically occurs during sleep and
      more specifically during REM sleep. STATE OF THE ART: During obstructive chronic
      respiratory failures, increases in PaCO2 that are associated with REM sleep can
      participate to the severity of daytime hypercapnia and in a subgroup of patients
      lead to an indication of nocturnal non-invasive ventilation (NIV) in association
      with the long-term oxygen therapy. A REM sleep hypoventilation generally appears
      during the early course of restrictive chronic respiratory failures. This REM
      sleep hypoventilation represents one of the most frequent reasons for initiating
      NIV in restrictive respiratory insufficiencies. Obesity-hypoventilation syndrome
      (OHS) refers to a hypercapnic chronic respiratory failure in which REM sleep
      hypoventilation is one of the main determinants. In France, in 2004, OHS is the
      primary chronic respiratory failure leading to at home NIV. NIV on OHS aims to
      maintain upper airway patency as sleep apnoea is frequently associated and to
      allow sufficient alveolar ventilation during REM sleep. PERSPECTIVES: Thus, sleep
      alveolar hypoventilation should be systematically assessed in obese patients and
      during the time curse evolution of all the chronic respiratory failures. This can
      be done relatively easily by using nocturnal oximetry concurrently with a
      transcutaneous PCO2 measurement. CONCLUSION: The understanding of exact
      mechanisms underlying abnormal respiratory events occurring during sleep allows
      optimising adjustments in NIV parameters.

PMID- 15968765
TI  - [The place of routine immediate non-invasive ventilation following pulmonary
      resection in preventing pulmonary complications in patients with COPD (POPVNI
      Trial)].
AB  - BACKGROUND: Respiratory complications are common following pulmonary resection
      and cause a significant mortality. The use of non-invasive ventilation (NIV) in
      acute respiratory insufficiency (ARI) is now well recognised. The prophylactic
      use of NIV in the absence of ARI and/or hypercapnia may be equally justified for
      the physiological benefits expected in the post-operative period following
      pulmonary surgery. The aim of our study therefore is to evaluate the
      effectiveness of NIV in the prevention of pulmonary complications in the
      immediate post-operative care of patients with moderate and severe COPD. METHODS:
      It will be a multicentre, prospective, randomised, parallel, open ended study of
      patients with moderate and severe COPD admitted to hospital for pulmonary
      resection. EXPECTED RESULTS: To determine whether the setting up of NIV
      immediately post-operatively reduces the incidence of acute respiratory events
      (acute respiratory insufficiency) and to identify any sub-groups who receive
      greater benefit from NIV. This study should establish the place of NIV in the
      immediate post operative care following pulmonary resection.

PMID- 15968766
TI  - [Asymptomatic forms of the Severe Acute Respiratory Syndrome (SARS)].
AB  - INTRODUCTION: In November 2002 an epidemic of atypical pneumonia appeared in the
      Chinese region of Guandong. It was subsequently given the name "Severe Acute
      Respiratory Syndrome" (SARS) following the occurrence of further outbreaks in
      Hanoi and Hong Kong in February 2003. Five cases related to the same patient
      source have been reported in France. CASE REPORT: We report the case of a patient
      of 52 years who had direct contact with a probable case of SARS. On admission the
      patient presented with pyrexia associated with lymphopenia and liver cell
      necrosis but no respiratory symptoms. The chest x-ray was normal. The thoracic CT
      scan showed a sub pleural ground glass appearance. Early (36 hours) PCR studies
      of nasopharyngeal washings were negative for the coronavirus associated with
      SARS. The diagnosis was confirmed serologically. CONCLUSIONS: This observation
      demonstrates the existence of incomplete clinical presentations of SARS. The
      infectivity of this asymptomatic form is unknown. Serological analyses will allow
      better identification. The continuing danger of seasonal recurrence, particularly
      in the winter, cannot be ignored. In this context the recognition of probably
      infectious asymptomatic forms is essential.

PMID- 15968767
TI  - [Devic's optic neuromyelitis and pulmonary tuberculosis].
AB  - INTRODUCTION: Optic neuromyelitis or Devic's syndrome is a very rare disease
      affecting the optic tracts and the spinal cord. Its association with evolving
      pulmonary tuberculosis has been noted in a handful of case reports. CASE REPORT:
      The authors reportthe case of a 40 year old patient with evolving pulmonary
      tuberculosis who experienced bilateral blindness followed by paraplegia and
      sphincter disturbance. Clinical examination and investigations excluded direct
      tuberculous involvement of the nervous system or a reaction to antituberculous
      therapy and Devic's syndrome was diagnosed, based on Wingerchurk's criteria.
      Following treatment with corticosteroids and antituberculous chemotherapy, the
      patient recovered normal mobility and sphincter control but remained completely
      blind. CONCLUSIONS: Throughout this case report, the authors emphasise the rarity
      of this association and discuss the pathophysiological mechanism, which appears
      to be an immune dysfunction triggered by mycobacterial infection.

PMID- 15968768
TI  - [Pneumoperitoneum and pneumomediastinum complicating non-invasive ventilation].
AB  - INTRODUCTION: Pneumoperitoneum is known to be a rare complication of invasive
      mechanical ventilation. However it has not previously been described as a
      consequence of non-invasive ventilation. CASE REPORT: The authors report a case
      of pneumoperitoneum associated with pneumomediastinum occurring in a 64-year-old
      patient treated for 3 years with bilevel ventilation via a nasal mask (expiratory
      pressure = 9 cm H2O, inspiratory pressure = 15 cm H2O) for obesity
      hypoventilation syndrome. Respiratory and gastroenterological investigations did
      not demonstrate a cause for this complication which resolved spontaneously
      following the cessation of ventilation. Nine months later, clinical deterioration
      and a worsening of blood gas parameters led to a recommencement of non-invasive
      mechanical ventilation at the same levels as previously. Over two years of follow
      up there have been no clinical or radiological signs of a recurrence of
      pneumomediastinum or pneumoperitoneum. CONCLUSION: In the absence of any other
      explanation, barotrauma due to nasal ventilation appears to be the most likely
      explanation for this complication.

PMID- 15968769
TI  - [A fortuitous discovery with severe consequences].

PMID- 15968770
TI  - [Domicilary ventilation in three countries].

PMID- 15968771
TI  - [Homogeneising the respiratory care of ALS patients in France].

PMID- 15968772
TI  - [Logistic regression].

PMID- 15968773
TI  - [Electrophysiological methods for the assessment of respiratory muscles].

PMID- 15968774
TI  - [Venous thromboembolism].

PMID- 15968775
TI  - [Clinical practice guidelines AFSSAPS-ANAES. Follow-up of the adult asthmatic
      patient].

PMID- 15968776
TI  - [Tobacco smoking and pregnancy].

PMID- 15968777
TI  - [Recent advances in biological andrology].

PMID- 15968778
TI  - [News on spermatogenesis].

PMID- 15968779
TI  - [Exploration of sterile men in the era of ICSI].

PMID- 15968780
TI  - [Genetic aspects of male sterility].

PMID- 15968781
TI  - [Cryptozoospermia: biopsy or ejaculation?].

PMID- 15968782
TI  - [The surgical sampling of spermatozoids].

PMID- 15968783
TI  - [Experience with synchronous surgical sampling].

PMID- 15968784
TI  - [Experience with asynchronous biopsy: ICSI with spermatozoids of testicular
      origin].

PMID- 15968785
TI  - [ICSI: can one select the spermatozoids?].

PMID- 15968786
TI  - [Fragmentation of spermatic DNA and its implication in AMP].

PMID- 15968787
TI  - [The interest of the chromosomic study of spermatozoids].

PMID- 15968788
TI  - [In vitro maturation of male germ cells].

PMID- 15968789
TI  - [Haploidisation of somatic cells].

PMID- 15968790
TI  - [Testicular tissue grafting].

PMID- 15968792
TI  - [Structure, action and recruitment of the respiratory muscles during exercise].

PMID- 15968793
TI  - [How is respiratory muscle function controlled?].

PMID- 15968794
TI  - [Are the respiratory muscles usual skeletal muscles?].

PMID- 15968795
TI  - [First line assessment of respiratory muscle function].

PMID- 15968796
TI  - [Specialised assessment of respiratory muscle function].

PMID- 15968797
TI  - [Loco-motor muscles in chronic respiratory diseases: the example of COPD].

PMID- 15968798
TI  - [The internist and respiratory muscles: when should respiratory muscles be
      explored?].

PMID- 15968799
TI  - [Practical management of the elevated hemidiaphragm].

PMID- 15968800
TI  - [Neuromuscular diseases in adults: which respiratory muscle explorations for what
      type of management?].

PMID- 15968802
TI  - [The interest of animal models for the understanding of respiratory muscle
      dysfunction].

PMID- 15968801
TI  - [Assessment of respiratory muscle function in the ICU].

PMID- 15968803
TI  - "Cafe Terrace at Night" (1888), Vincent van Gogh.

PMID- 15968804
TI  - [Professor B.E. Linberg (the 120th anniversary of birth)].

PMID- 15968805
TI  - Toward a clinical understanding of bipolar disorders: classification and
      presentation.
AB  - This review describes the clinical spectrum of bipolar disorder and its
      classification in the Diagnostic and Statistical Manual of Mental Disorders (DSM)
      IV and the International Classification of Diseases (IACD)-10. The development of
      new diagnostic trends and their clinical implications are discussed.

PMID- 15968806
TI  - Epidemiology of bipolar disorders.
AB  - Bipolar, or manic-depressive, disorders are frequent and severe mental illnesses
      associated with considerable morbidity and mortality. Epilepsy and bipolar
      disorder could probably share some aspects of pathophysiology because manic as
      well as depressive symptoms are seen in patients with seizures, and a number of
      antiepileptic drugs are effectively used in the acute and prophylactic treatment
      of bipolar disorder. Epidemiologic research suggests a dimensional composition of
      bipolar illness at the population level. Apart from the DSM-IV diagnostic
      features of bipolar I (mania and depression) and bipolar II (hypomania and
      depression), the concept of bipolar spectrum disorders comprises a range of
      bipolar conditions with less obvious manifestations with estimated lifetime
      prevalence rates ranging from 2.8 to 6.5%. Expanding the definition of bipolar II
      disorders shows that half of the patients currently diagnosed with a unipolar
      depressive episode could suffer from unrecognized bipolar II disorder, and about
      the same number of mild depressive patients could be minor bipolars. Research
      efforts to refine the diagnostic criteria of bipolar disorder aim at an earlier
      and complete recognition of the disease to provide appropriate pharmacological
      and nonpharmacological treatment early in the course of the illness to anticipate
      individual suffering, suicidal behavior, and increased socioeconomic costs for
      society. This article also discusses risk factors, comorbid conditions, course of
      illness, as well as the individual and socioeconomic impact of bipolar disorders.
      CONCLUSIONS: The findings suggest reconceptualizing bipolar illnesses as highly
      recurrent, malignant disorders that occur far more frequently than previously
      thought. Interdisciplinary knowledge transfer could help to increase our
      understanding of the pathophysiology of these disorders as well as provide
      grounds for better recognition and treatment of patients with manic and/or
      depressive symptoms.

PMID- 15968807
TI  - An introduction to antiepileptic drugs.
AB  - In recent years, the number of commercially available antiepileptic drugs (AEDs)
      has increased steadily. Although this may complicate management choices, it also
      offers welcome new options to individualize treatment more effectively. Because
      each of the available AEDs differs from others in many clinically relevant
      properties, opportunities to tailor drug treatment to the characteristics of the
      individual patient have never been greater. Properties that are especially
      important in drug selection in patients with epilepsy include spectrum of
      efficacy in different seizure types, adverse effects profile, pharmacokinetic
      properties, susceptibility to cause or be a target of clinically important drug
      drug interactions, ease of use, and cost. Other factors that need to be
      considered in tailoring drug choice include availability of user-friendly
      pediatric formulations, and potentially favorable effects on co-morbid
      conditions. In fact, a number of AEDs are efficacious and widely prescribed in
      additional indications, particularly psychiatric disorders, migraine prophylaxis,
      and neuropathic pain. Recently, advances have been made in understanding the
      mechanisms of actions of AEDs at the molecular level. While a fully mechanistic
      approach to the clinical use of these agents is not yet feasible, knowledge of
      mechanisms of action offers useful clues in predicting their efficacy profile and
      spectrum of potential adverse effects.

PMID- 15968808
TI  - Antiepileptic drugs in mood-disordered patients.
AB  - Bipolar disorder is a common, recurrent, often severe mental disorder that,
      without adequate treatment, is associated with high rates of morbidity and
      mortality. We review the evidence on the efficacy of a spectrum of antiepileptic
      drugs (AED) in bipolar disorder. Most studies have been carried out with
      carbamazepine (CBZ), valproate (VPA), and lamotrigine (LTG). All three of these
      AEDs have been shown to be of value in the management of patients with bipolar
      illnesses. VPA and CBZ seem to exert stronger antimanic effects and, to a lesser
      degree, acute antidepressant efficacy. LTG seems to be effective against
      depression and mania, with a more robust activity against depression. No firm
      evidence supports a role for vigabatrin, tiagabine, topiramate, or levetiracetam
      in these disorders.

PMID- 15968809
TI  - Antiepileptic drugs and the regulation of mood and quality of life (QOL): the
      evidence from epilepsy.
AB  - We review the literature on the influence of antiepileptic drugs (AEDs) on mood
      and quality of life in patients with epilepsy. Although many anecdotal reports
      cover a spectrum of AEDs, most of the controlled data have come from studies of
      carbamazepine and lamotrigine. Both of these compounds appear to have positive
      effects on mood, and these data parallel the effects noted in nonepilepsy
      populations. AEDs that are gamma-aminobutyric acid (GABA)ergic tend to have
      negative effects on mood, and an affective disorder is often noted as a treatment
      emergent effect. It is speculated that the amygdala is an important anatomic
      structure in the cerebral circuits that regulate mood in affective disorders but
      also in epilepsy, and an effect of AEDs on such circuits aids mood stability in
      both populations of patients.

PMID- 15968810
TI  - Ask us: Some drugs affect tooth movement.

PMID- 15968811
TI  - The creativity of clinical medicine.

PMID- 15968812
TI  - Mediator deathwork.
AB  - The most discussed and analyzed form of deathwork is the dyadic therapist--client
      relationship, but this far from exhausts the various types of professional work
      involving the dead. Mediator deathwork is where the professional gleans or
      constructs information about the dead, edits and polishes it, and publicly
      presents the edited version in a public rite; this entails a triadic flow of
      information: the dead--the mediator--public rite. Examples include pathologists,
      coroners, American funeral directors, funeral celebrants, obituary writers,
      spiritualist mediums, and museum curators. Other types include barrier deathwork
      (in which the professional insulates the living from the dead--the dead | the
      living--as in British funeral directing), and intercessory deathwork in which
      priests send prayers the other way, from the living to, or on behalf of, the
      dead: mourner--priest--the dead. The article focuses on mediator deathwork
      because, though it is the most widespread form of deathwork, it is the least
      discussed and analyzed.

PMID- 15968813
TI  - An application of Durkheim's theory of suicide to prison suicide rates in the
      United States.
AB  - E. Durkheim (1897) suggested that the societal rate of suicide might be explained
      by societal factors, such as marriage, divorce, and birth rates. The current
      study examined male prison suicide rates and suicide rates for men in the total
      population in the United States and found that variables based on Durkheim's
      theory of suicide explained prison suicide rates better than suicide rates for
      total population. Possible reasons for these findings are discussed.

PMID- 15968814
TI  - Synthesis and antimycobacterial activity of 7-O-substituted-4-methyl-2H-2
      chromenone derivatives vs Mycobacterium tuberculosis.
AB  - A series of 7-O-alkoxy-4-methylumbelliferone derivatives were prepared using a
      convenient one step synthesis. Additionally the bromo- and azido derivatives 7-O
      (4-bromobutoxy)-, 7-O-(6-bromohexyloxy)- and 7-O-(6-azidohexyloxy)-4
      methylumbelliferone derivatives were prepared. In vitro evaluation of
      antimycobacterial activity determined % inhibition and MIC vs M. tuberculosis
      H37Rv with toxicity (IC50) assessed in VERO cells. The coumarins with longer
      alkyl chains (nonyl and decyl) showed the optimum inhibitory activity in this
      series (MIC 3.13 microg/mL) and IC50 > 10 microg/mL.

PMID- 15968815
TI  - Anticandidal properties of N-acylpeptides containing an inhibitor of glucosamine
      6-phosphate synthase.
AB  - A series of N-acyl peptides 1-9, containing an inhibitor of glucosamine-6
      phosphate synthase have been synthesised and tested against Candida strains. N
      Acylated peptides inhibit glucosamine-6-phosphate synthase in cell free extracts
      from Candida albicans. Antifungal activities of the tested compounds correlated
      with their lipophilic properties. Peptides acylated with decanoic acid were found
      to be the most potent in the series. N-decanoylpeptides also showed activity
      against Candida albicans Gu5 resistant mutant with Cdr1 and Cdr2 drug extrusion
      proteins that causes MDR by an active efflux mechanism.

PMID- 15968816
TI  - Potent inhibition of chitin synthase by an azasugar--investigation of synergistic
      effect with UDP.
AB  - We identified 6-deoxy-homoDMDP as a potent inhibitor of chitin synthase (Ki = 38
      microM), displaying an uncompetitive inhibition pattern. Dual inhibition was also
      performed with the enzymatic reaction product uridine 5'-diphosphate in order to
      evaluate the concurrent effect of both inhibitors. An interaction coefficient
      alpha of 0.9 was found, revealing synergistic inhibition.

PMID- 15968817
TI  - Molecular mechanics PBSA ligand binding energy and interaction of Efavirenz
      derivatives with HIV-1 reverse transcriptase.
AB  - In order to evaluate the properties of several HIV-1 reverse transcripase(RT)
      inhibitors, Efavirenz (SUSTIVA) and a set of its derivatives (benzoxazinones)
      have been placed into the nonnucleoside analogue binding site of the enzyme by
      molecular docking. The resulting geometries were used for a molecular dynamics
      simulation and binding energy calculations. The enzyme-inhibitor binding energies
      were estimated from experimental inhibitory activities (IC90). The correlation of
      the predicted and experimental binding energies were satisfactory acceptable as
      indicated by r2 = 0.865. Based on MD simulations, the obtained results indicate
      that the tight association of the ligand to the HIV-1 RT binding pocket was based
      on hydrogen bonding between Efavirenz's N1 and the oxygen of the backbone of Lys
      101, with an estimated average distance of 1.88 A. Moreover, electrostatic
      interaction was mainly contributed by two amino acid residues in the binding
      site; Lys 101 and His 235. MD simulations open the possibility to study the
      reaction of the flexible enzyme to those substances as well as the overall
      affinity.

PMID- 15968818
TI  - Benzofuran- and furan-2-yl-(phenyl)-3-pyridylmethanols: synthesis and inhibition
      of P450 aromatase.
AB  - A series of benzofuran-2-yl-(phenyl)-3-pyridylmethanol derivatives were prepared
      using an efficient 1-step procedure in good yields. In addition furan-2-yl
      (phenyl)-3-pyridylmethanol derivatives were also prepared to determine the effect
      of the benzene ring in benzofuran with respect to inhibitory activity. The
      pyridylmethanol derivatives were all evaluated in vitro for inhibitory activity
      against aromatase (P450(AROM), CYP19), using human placental microsomes. The
      benzofuran-2-yl-(phenyl)-3-pyridylmethanol derivatives showed good to moderate
      activity (IC50 = 1.3-25.1 microM), which was either better than or comparable
      with aminoglutethimide (IC50 = 18.5 microM) but lower than arimidex (IC50 = 0.6
      microM), with the 4-methoxyphenyl substituted derivative displaying optimum
      activity. Molecular modelling of the benzofuran-2-yl-(4-fluorophenyl)-3
      pyridylmethanol derivative suggested activity to reside with the (S)-enantiomer.
      The furan-2-yl-(phenyl)-3-pyridylmethanol derivatives were devoid of activity
      indicating the essential role of the benzene ring of the benzofuran component for
      enzyme binding.

PMID- 15968819
TI  - Reactions of plant copper/topaquinone amine oxidases with N6-aminoalkyl
      derivatives of adenine.
AB  - Plant copper/topaquinone-containing amine oxidases (CAOs, EC 1.4.3.6) are enzymes
      oxidising various amines. Here we report a study on the reactions of CAOs from
      grass pea (Lathyrus sativus), lentil (Lens esculenta) and Euphorbia characias, a
      Mediterranean shrub, with N6-aminoalkyl adenines representing combined analogues
      of cytokinins and polyamines. The following compounds were synthesised: N6-(3
      aminopropyl)adenine, N6-(4-aminobutyl)adenine, N6-(4-amino-trans-but-2-enyl)
      adenine, N6-(4-amino-cis-but-2-enyl) adenine and N6-(4-aminobut-2-ynyl) adenine.
      From these, N6-(4-aminobutyl) adenine and N6-(4-amino-trans-but-2-enyl)adenine
      were found to be substrates for all three enzymes (Km approximately 10(-4)M).
      Absorption spectroscopy demonstrated such an interaction with the cofactor
      topaquinone, which is typical for common diamine substrates. However, only the
      former compound provided a regular reaction stoichiometry. Anaerobic absorption
      spectra of N6-(3-aminopropyl)adenine, N6-(4-amino-cis-but-2-enyl)adenine and N6
      (4-aminobut-2-ynyl)adenine reactions revealed a similar kind of initial
      interaction, although the compounds finally inhibited the enzymes. Kinetic
      measurements allowed the determination of both inhibition type and strength; N6
      (3-aminopropyl)adenine and N6-(4-amino-cis-but-2-enyl)adenine produced reversible
      inhibition (Ki approximately 10(-5) - 10(-4) M) whereas, N6-(4-aminobut-2
      ynyl)adenine could be considered a powerful inactivator.

PMID- 15968820
TI  - Inhibitors of type 1 17beta-hydroxysteroid dehydrogenase with reduced estrogenic
      activity: modifications of the positions 3 and 6 of estradiol.
AB  - Breast cancer is the second most frequent cancer affecting women. Among all
      endocrine therapies for the treatment of breast cancer, inhibition of estrogen
      biosynthesis is becoming an interesting complementary approach to the use of
      antiestrogens. The enzyme type 1 17beta-hydroxysteroid dehydrogenase (17beta-HSD)
      plays a critical role in the biosynthesis of estradiol catalyzing preferentially
      the reduction of estrone into estradiol, the most active estrogen. Consequently,
      this enzyme is an interesting biological target for designing drugs for the
      treatment of estrogen-sensitive diseases such as breast cancer. Our group has
      reported the synthesis and the biological evaluation of N-methyl, N-butyl 6beta
      (thiaheptamamide)estradiol as a potent reversible inhibitor of type 1 17beta-HSD.
      Unfortunately, this inhibitor has shown an estrogen effect, thus reducing its
      possible therapeutic interest. Herein three strategies to modify the biological
      profile (estrogenicity and inhibitory potency) of the initial lead compound were
      reported. In a first approach, the thioether bond was replaced with a more stable
      ether bond. Secondly, the hydroxyl group at position 3, which is responsible for
      a tight binding with the estrogen receptor, was removed. Finally, the amide group
      of the side-chain was changed to a methyl group. Moreover, the relationship
      between the inhibitory potency and the configuration of the side-chain at
      position 6 was investigated. The present study confirmed that the 6beta
      configuration of the side chain led to a much better inhibition than the 6alpha
      configuration. The replacement of the 3-OH by a hydrogen atom as well as that of
      the amide group by a methyl was clearly unfavorable for the inhibition of type 1
      17beta-HSD. Changing the thioether for an ether bond decreased by 10-fold the
      estrogenic profile of the lead compound while the inhibitory potency on type 1
      17beta-HSD was only decreased by 5-fold. This study contributes to the knowledge
      required for the development of compounds with the desired profile, that is, a
      potent inhibitor of type 1 17beta-HSD without estrogen-like effects.

PMID- 15968821
TI  - Synthesis and structure-activity relationships of analogs of EM-652 (acolbifene),
      a pure selective estrogen receptor modulator. Study of nitrogen substitution.
AB  - EM-652 (acolbifene) analogs have been synthesized as selective estrogen receptor
      modulators. Substitution on the nitrogen atom of these 2H-1-benzopyran
      derivatives has been studied for its influence on antiestrogenic activity.
      Binding to the rat estrogen receptor, inhibition of estradiol-stimulated
      proliferation of T-47D breast cancer cells, as well as antiuterotrophic and
      uterotrophic activities in ovariectomized mice have been evaluated. 2H-1
      Benzopyran 1b (EM-343, racemic form of EM-652), which contains a piperidine ring,
      shows the best pharmacological profile; RBA = 380, IC50 value = 0.110 nM (in T
      47D cells), as well as 63% and 84% antiuterotrophic inhibitions at the 7.5 and 75
      nmol doses, respectively.

PMID- 15968823
TI  - In-vitro antibacterial, antifungal and cytotoxic properties of sulfonamide-
      derived Schiff's bases and their metal complexes.
AB  - A series of new antibacterial and antifungal Schiff's bases derived from
      sulfonamides, as well as their transition metal complexes incorporating cobalt
      (II), copper (II), nickel (II) and zinc (II) were synthesized, characterized and
      screened for their in-vitro antibacterial activity against six Gram-negative
      (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas
      aeruginosa, Salmonella typhi and Shigella dysentriae) and four Gram-positive
      (Bacillus cereus, Corynebacterium diphtheriae, Staphylococcus aureous and
      Streptococcus pyogenes) bacterial strains and for in-vitro antifungal activity
      against Trichophyton longifusus, Candida albicans, Aspergillus flavus,
      Microsporum canis, Fusarium solani, Candida glaberata. The results of these
      studies show the metal complexes to be more antibacterial and antifungal as
      compared to the uncomplexed Schiffs' bases. The brine shrimp bioassay was also
      carried out to study the in-vitro cytotoxic properties of these synthesized
      ligands and their complexes.

PMID- 15968822
TI  - Synthesis and antituberculosis activity of new 3-alkylsulfanyl-1,2,4-triazole
      derivatives.
AB  - The increasing clinical importance of drug-resistant mycobacterial pathogens has
      lent additional urgency to microbiological research and new antimycobacterial
      compound development. For this purpose, new alkylsulfanyltriazoles were
      synthesized and evaluated for antituberculosis activity. The reaction of thienyl
      2-acetic acid with thiocarbohydrazide gave the mercaptotriazoles (II). The 4
      amino-5-(2-thienylmethyl)-3-[1-(2-thienyl)-3-aryl) propion-3-yl] sulfanyl-4H
      1,2,4-triazole (III) derivatives were synthesized by reacting the
      mercaptotriazoles with chalcones (I). Antituberculosis activities of the
      synthesized compounds were determined by broth microdilution assay, the
      Microplate Alamar Blue Assay, in BACTEC 12B medium and results were screened in
      vitro, using BACTEC 460 Radiometric System against Mycobacterium tuberculosis
      H37Rv (ATCC 27294) at 6.25 microg/ml and the tested compounds showed considerable
      inhibition ranging from 58-84%.

PMID- 15968824
TI  - Trypanocidal activity of N-isopropyl oxamate on cultured epimastigotes and murine
      trypanosomiasis using different Trypanosoma cruzi strains.
AB  - The trypanocidal activity of N-isopropyl oxamate (NIPOx) and the ethyl ester of N
      isopropyl oxamate (Et-NIPOx) were tested on cultured epimastigotes (in vitro) and
      on murine trypanosomiasis (in vivo) using five different T. cruzi strains. When
      benznidazole and nifurtimox, used for comparison, were tested we found that only
      three of these T. cruzi strains were affected, whereas the other two strains,
      Miguz and Compostela, were resistant to the in vitro and the in vivo trypanocidal
      activity of these substances. In addition, when NIPOx was tested on cultured
      epimastigotes and on mice parasitaemia, trypanocidal activity was not obtained on
      either of these T. cruzi strains. Our experiments strongly suggest that NIPOx
      does not penetrate intact epimastigotes due to the polarity of its carboxylate
      whereas Et-NIPOx, acting as a prodrug, exhibited in vitro and in vivo
      trypanocidal activity in the five tested T. cruzi strains.

PMID- 15968825
TI  - Beta-alanine suppresses heat inactivation of lactate dehydrogenase.
AB  - Beta-Alanine exhibits neurotransmitter activity and is a component of the anti
      glycation agent carnosine. We propose that beta-alanine may have additional
      properties which may be of physiological significance. Interestingly, stress
      modulates the level of beta-alanine, which regulates excitotoxicity responses and
      prevents neuronal cell death. We hypothesize that beta-alanine's protective role
      may involve preservation of enzyme structure and function, suggesting that beta
      alanine may act as a chemical chaperone. We used light scattering, enzyme
      activity and intrinsic fluorescence to monitor heat-induced changes in lactate
      dehydrogenase (LDH) in the presence and absence of beta-alanine. We observed that
      beta-alanine suppressed heat-induced LDH inactivation, prevented LDH aggregation,
      ameliorated the decrease in intrinsic fluorescence and reactivated thermally
      denatured LDH. These observations support the hypothesis that beta-alanine has
      chaperone-like activity and may play a cellular role in the preservation of
      enzyme function.

PMID- 15968826
TI  - Triton X-100 inhibition of yeast plasma membrane associated NADH-dependent redox
      activities.
AB  - Plasma membrane (PM) vesicles isolated from the yeast Saccharomyces cerevisiae
      (wild-type NCIM 3078, and a MG 21290 mutant pma 1-1) were used to monitor the
      effect of the detergents, 3-[(3-cholamidopropyl) dimethylammonio]-1-propane
      sulfonate (Chaps) and Triton X-100, on (H+)-ATPase (E.C. 3.6.1.35), NADH oxidase
      and NADH-hexacynoferrate (III)[HCF (III)] oxidoreductase (E.C. 1.6.99.3)
      activities. The results obtained show that Triton X-100 inhibited both membrane
      bound and solubilized NADH-dependent redox activities. The nature of this
      inhibition as determined for NADH-HCF(III) oxidoreductase was non-competitive and
      the Ki values for wild and mutant enzymes were 1.2 x 10(-5) M and 8.0 x 10(-6) M,
      respectively. The findings are interpreted, in view of the established reports,
      that the active site architecture of PM bound NADH-dependent oxidoreductase in
      yeast is likely to be different than in other eukaryotes.

PMID- 15968827
TI  - Food toxicology--from forensic to policy tool: an evolution from reactive to
      proactive action.
AB  - Since the nineteenth century, food toxicology has evolved in several ways. The
      analytical power of the food toxicologist has been increased. The concept of
      adulterated food was modified significantly. Most commodities are now processed
      and addition of numerous non-nutrient additives is legalised. Other "alien"
      compounds get introduced in the food chain from background contamination or
      during processing and distribution. This makes the task of the food toxicologist
      more complex. From forensic science food toxicology developed to a policy aid.

PMID- 15968828
TI  - Evaluation of the rodent Hershberger bioassay using three reference
      (anti)androgens.
AB  - Under the umbrella of the Organization for Economic Cooperation and Development
      (OECD) the rodent Hershberger bioassay is being validated as an in vivo screen
      for the detection of (anti)androgens. As part of the validation work we studied
      trenbolone (TREN), 1,1-bis-(4-chlorophenyl)-2,2-dichloroethylene (p,p'-DDE) and
      vinclozolin (VIN). Oral intubation of castrated rats with TREN [0.3-1.5-8-40 mg
      kg(-1) body weight (b.w.)] for ten days increased androgen-sensitive tissue
      weights (ASTW) at the high dose. p,p'-DDE (5-16-50-160 mg kg(-1) b.w.) and VIN (0
      3-10-30-100 mg kg(-1) b.w.) orally administered for ten days produced a dose
      dependent decrease in ASTW in castrated rats subcutaneously supplemented with
      testosterone propionate (0.4 mg kg(-1) b.w.). p,p'-DDE also strongly increased
      liver weights and induced hepatocellular hypertrophy and thyroid follicular cell
      hypertrophy that was most likely mediated by liver enzyme induction. Our data
      strongly suggest that the OECD protocol of the rodent Hershberger bioassay
      describes a sensitive in vivo screen, capable of detecting weakly active
      (anti)androgens. Furthermore, our data may also indicate that thyroid effects
      could be assessed, if the protocol is amended accordingly.

PMID- 15968829
TI  - Examining the suitability of mussel digestive gland to serve as a biomonitoring
      target organ.
AB  - In coastal marine areas, the level of metallothioneins (MTs) is monitored as the
      specific response to trace heavy metals and is considered as a biomarker of metal
      exposure. Laboratory experiments with bivalves indicate that MT synthesis is
      induced by Cd, Cu, Hg, Ag and Zn ions. The results of our study, conducted with
      the mussel Mytilus galloprovincialis, deployed 12 months in the "hot spot" area
      of the Kastela Bay, Dalmatia, Croatia, are evaluated considering the
      recommendation of MED POL Programme for estimating exposure of mussels to trace
      heavy metals by means of MTs. Our data clearly indicate that the MT level in the
      digestive gland of the Mediterranean mussel depends on the biotic and abiotic
      parameters. Beside MT level, a number of parameters, like digestive gland mass,
      shell mass, cytosolic metal concentration is needed in order to define if MT
      level in the digestive gland of mussels is indicative as a biomarker of cadmium
      exposure.

PMID- 15968830
TI  - In vivo effects of maternal immunosuppression during pregnancy on the immune
      function of newborn infants.
AB  - When used in pregnancy, immunosuppressants can cross the placental barrier and
      enter foetal circulation, possibly affecting the immune system of the foetus.
      This study evaluated the immune function in eight children born by mothers with
      connective tissue diseases who received immunosuppressants (cyclosporine A or
      dexamethasone) during pregnancy and in six babies from mothers with similar
      diseases, but who did not receive any treatment. Judging by the cytokine
      production of interleukin-2 and interferon-gamma in peripheral blood mononuclear
      cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin,
      immunosuppressive drugs given for rheumatic disorders during pregnancy do not
      induce significant immunosuppression in babies.

PMID- 15968831
TI  - Margins of safety of intravascular contrast media: body weight, surface area or
      toxicokinetic approach?
AB  - The margin of safety of a drug is defined as the ratio between toxicity in
      animals and safety in humans. For intravascular contrast media, the margin of
      safety is traditionally the ratio between LD50 and diagnostic dose, both doses
      being based on bodyweight. The shift to surface area dramatically reduces this
      margin to unacceptable values. Toxicokinetics, which relates systemic exposure
      associated with early toxic signs in animals to plasma level in man, seems the
      most accurate and predictive criterion.

PMID- 15968832
TI  - The precautionary principle.
AB  - The Precautionary Principle in its simplest form states: "When an activity raises
      threats of harm to human health or the environment, precautionary measures should
      be taken even if some cause-and-effect relationships are not fully established
      scientifically". This Principle is the basis for European environmental law, and
      plays an increasing role in developing environmental health policies as well. It
      also is used in environmental decision-making in Canada and in several European
      countries, especially in Denmark, Sweden, and Germany. The Precautionary
      Principle has been used in the environmental decision-making process and in
      regulating drugs and other consumer products in the United States. The
      Precautionary Principle enhances the collection of risk information for, among
      other items, high production volume chemicals and risk-based analyses in general.
      It does not eliminate the need for good science or for science-based risk
      assessments. Public participation is encouraged in both the review process and
      the decision-making process. The Precautionary Principle encourages, and in some
      cases may require, transparency of the risk assessment process on health risk of
      chemicals both for public health and the environment. A debate continues on
      whether the Principle should embrace the "polluter pays" directive and place the
      responsibility for providing risk assessment on industry. The best elements of a
      precautionary approach demand good science and challenge the scientific community
      to improve methods used for risk assessment.

PMID- 15968833
TI  - New aspects in the classification of carcinogens.
AB  - The existing systems of classification of carcinogens should include a
      distinction between genotoxic and non-genotoxic chemicals. For non-genotoxic
      chemicals, permissible exposure levels can be derived at which no relevant human
      cancer risks are anticipated. While genotoxic carcinogens can induce chromosomal
      effects without mutagenic action, non-DNA-reactive genotoxins affecting
      topoisomerase or the spindle, or those having an exclusively aneugenic effect can
      be carcinogenic only at high, toxic doses. Specific mechanisms of clastogenicity
      and processes of carcinogenesis based on reactive oxygen have practical
      thresholds. Since reactive oxygen species (ROS) are generally genotoxic, the
      question is whether chemicals that increase ROS production will add to
      endogenously produced background levels and lead to nonlinear dose-effect
      relationships. Taking into account the presence of endogenous carcinogens, it is
      now becoming evident that carcinogenic risk extrapolation to low doses must be
      considered according to the mode of action.

PMID- 15968834
TI  - Plant genotoxicity: a molecular cytogenetic approach in plant bioassays.
AB  - It is important for the prevention of DNA changes caused by environment to
      understand the biological consequences of DNA damages and their molecular modes
      of action that lead to repair or alterations of the genetic material. Numerous
      genotoxicity assay systems have been developed to identify DNA reactive
      compounds. The available data show that plant bioassays are important tests in
      the detection of genotoxic contamination in the environment and the establishment
      of controlling systems. Plant system can detect a wide range of genetic damage,
      including gene mutations and chromosome aberrations. Recently introduced
      molecular cytogenetic methods allow analysis of genotoxicity, both at the
      chromosomal and DNA level. FISH gives a new possibility of the detection and
      analysis of chromosomal rearrangements in a great detail. DNA fragmentation can
      be estimated using the TUNEL test and the single cell gel electrophoresis (Comet
      assay).

PMID- 15968835
TI  - Food safety evaluation of crops produced through genetic engineering--how to
      reduce unintended effects?
AB  - Scientists started applying genetic engineering techniques to improve crops two
      decades ago; about 70 varieties obtained via genetic engineering have been
      approved to date. Although genetic engineering offers the most precise and
      controllable genetic modification of crops in entire history of plant
      improvement, the site of insertion of a desirable gene cannot be predicted during
      the application of this technology. As a consequence, unintended effects might
      occur due to activation or silencing of genes, giving rise to allergic reactions
      or toxicity. Therefore, extensive chemical, biochemical and nutritional analyses
      are performed on each new genetically engineered variety. Since the unintended
      effects may be predictable on the basis of what is known about the insertion
      place of the transgenic DNA, an important aim of plant biotechnology is to define
      techniques for the insertion of transgene into the predetermined chromosomal
      position (gene targeting). Although gene targeting cannot be applied routinely in
      crop plants, given the recent advances, that goal may be reached in the near
      future.

PMID- 15968836
TI  - Alternative models for toxicity testing of xenobiotics.
AB  - The alternatives to whole-animal testing include endpoint assays, cell and tissue
      cultures, use of tissue slices, toxicokinetic modelling, and structure-activity
      relationships and databases. The use of in vitro systems (subcellular fractions,
      cell lines, primary cell cultures, tissue slices, organ cultures, etc.) as
      research tools in toxicology is widespread. In the past few years, the apoptosis
      phenomena were followed by very precise intracellular changes where, through
      programmed cell death, a cell can be removed from a population. The in vitro
      systems are ideally suited for investigations of the molecular, cellular and
      physiological mechanisms of chemically induced toxicity, which cannot readily be
      studied in vivo for known target organ and target species toxicity studies and
      for answering specific questions about toxic effects. The main justification for
      developing in vitro toxicity tests is that they will make toxicology a more
      scientifically based practice. It is increasingly apparent that the development
      and incorporation of stepwise testing strategies, combining experimental data
      from a range of alternative methods (physicochemical techniques, quantitative
      structure-activity relationships--QSAR, metabolic and kinetic modelling and in
      vitro tests), provide the most advanced way to predict toxicity, reducing at the
      same time the number of laboratory animals used for testing.

PMID- 15968837
TI  - The toxicology of bioregulators as potential agents of bioterrorism.
AB  - Bioregulators or modulators are biochemical compounds such as peptides, that
      occur naturally in organisms. Advances in biotechnology create the potential for
      the misuse of peptide bioregulators in offensive biological weapons programmes.
      Bioregulators are a new class of weapons that can damage the nervous system,
      alter mood, trigger psychological changes and kill. Over the last twenty years,
      neuroscience has produced an explosion of knowledge about receptor systems in the
      nerve cells that are of critical importance in receiving chemical transmitter
      substances released by other nerve cells. Bioregulators are closely related to
      substances normally found in the body that regulates normal biological processes.
      The potential military or terrorist use of bioregulators is similar to that of
      toxins. Together with increased research into toxins, the bioregulators have also
      been studied and synthesized. This paper presents a review of bioregulators that
      could be used in terrorist or other hostile activities.

PMID- 15968838
TI  - Cognitive-behavioural therapy for severe mental disorders.

PMID- 15968839
TI  - The negative symptoms of schizophrenia: a cognitive perspective.
AB  - Recent reports of improvement in the negative symptoms of schizophrenia following
      targeted cognitive interventions have prompted interest in the cognitive
      underpinnings of these symptoms. This review integrates current experimental
      research with the phenomenological accounts of patients participating in
      cognitive therapy for these specific symptoms. We propose that, in addition to
      the well-established role of neurobiological factors in their development and
      maintenance, specific cognitive appraisals and beliefs play a role in the
      expression and persistence of negative symptoms. This cognitive model of negative
      symptoms is based on a diathesis-stress formulation: a continuum of
      predispositional traits from the premorbid personality to the full-blown negative
      symptomatology, the incorporation of negative social and performance attitudes
      within these traits, and low expectancies for pleasure or success in goal
      oriented activities. We suggest that negative symptoms represent, in part, a
      compensatory pattern of disengagement in response to threatening delusional
      beliefs, perceived social threat, and anticipated failure in tasks and social
      activities. A psychological aspect of this motivational and behavioural inertia
      appears to be the patient's perception of limited psychological resources--a
      perception that motivates patients to conserve energy by minimizing investment in
      activities requiring effort.

PMID- 15968840
TI  - Functional cognitive-behavioural therapy: a brief, individual treatment for
      functional impairments resulting from psychotic symptoms in schizophrenia.
AB  - This paper describes a novel cognitive-behavioural approach to treating psychotic
      symptoms--functional cognitive-behavioural therapy (FCBT)--which was developed
      with the primary aim of remediating social functioning deficits in patients with
      residual psychotic symptoms. In FCBT, symptom-focused cognitive-behavioural
      therapy (CBT) interventions are delivered in the context of working on functional
      goals: a premise of FCBT is that the therapeutic alliance and patient motivation
      are enhanced by linking interventions to life goals. The paper outlines the
      rationale for expanding existing approaches to target social functioning
      impairment and uses case illustrations to exemplify particular phases of
      treatment as well as specific CBT interventions. Results from a pilot study of
      FCBT are summarized, together with suggestions for new research directions.

PMID- 15968841
TI  - Can patients with alcohol use disorders return to social drinking? Yes, so what
      should we do about it?

PMID- 15968842
TI  - Are attempts at moderate drinking by patients with alcohol dependency a form of
      Russian roulette?

PMID- 15968843
TI  - A study of HLA-linked genes in a monosymptomatic psychotic disorder in an Indian
      Bengali population.
AB  - OBJECTIVE: The etiology of delusional disorder is imperfectly understood.
      Involvement of biological factors has long been suspected. We examined the
      incidence of class I human leukocyte antigens (HLAs) in patients with delusional
      disorder to understand the role of HLA genes and explore a possible immunogenetic
      etiology for delusional disorder. METHODS: We used a nested case-control study
      design. Psychiatric reference data were available for 27 500 patients registered
      between 1998 and 2003. Initially, we enrolled 150 patients with delusional
      disorder from the India-born Bengali population, using DSM-IV diagnostic
      criteria. After longitudinal follow-up, 80 patients were found to have only
      delusional disorder, while the remaining 70 patients represented different
      illnesses with paranoid symptoms and were excluded. We performed serological
      typing on all 150 patients and applied the polymerase chain reaction-based high
      resolution molecular typing method to the 80 patients with delusional disorder.
      Eighty healthy donors of the same ethnic background, matched for age, sex, and
      other socioeconomic variables, formed the control group. RESULTS: Some of the HLA
      alleles were associated with delusional disorder, and the gene HLA-A*03 was found
      to be significantly more frequent. This gene may influence patients'
      susceptibility to delusional disorder. CONCLUSION: The study reveals important
      associations between HLA genes and delusional disorder. This preliminary
      observation may help our understanding of this disorder's genetic basis.

PMID- 15968844
TI  - An ecologic study of parasuicide in Edmonton and Calgary.
AB  - OBJECTIVE: From 1986 to 1999, the suicide rate in the Edmonton Regional Health
      Authority (RHA) was greater than that in the Calgary RHA (mean rate ratio 1.4).
      We conducted a study to determine whether a similar relation holds for
      parasuicide, and if so, whether the pattern can be explained at the ecologic
      level by sociodemographic factors. METHODS: The Edmonton and Calgary RHAs
      provided data on emergency department visits for nonfatal intentional self-injury
      for 1997. We obtained sociodemographic data from the 1996 national census for the
      Edmonton and Calgary census metropolitan areas (CMAs) from Statistics Canada's
      public-use files. In each CMA, which is nearly coterminous with the corresponding
      RHA, we created 10 geographic areas based on average income. We analyzed the data
      at the ecologic level, using linear regression and multilevel Poisson regression.
      RESULTS: The parasuicide rate in the Edmonton CMA was greater than that in the
      Calgary CMA (rate ratio 1.3). In both CMAs, the parasuicide rate decreased as
      average income increased. In the final regression models, the only independent
      variables were average income, CMA, and their interaction term (linear regression
      model R2 = 0.82). CONCLUSIONS: The parasuicide rate in the Edmonton CMA is
      elevated, compared with that in the Calgary CMA. At the ecologic level, much of
      the variation in rates can be explained by average income and CMA. The high
      degree of correlation among the sociodemographic variables suggests that it may
      not be low income per se that is affecting the parasuicide rate but, rather, the
      consequences of belonging to a socially disadvantaged stratum of society.

PMID- 15968845
TI  - Environmental cognitive remediation in schizophrenia: ethical implications of
      "smart home" technology.
AB  - OBJECTIVE: In light of the advent of new technologies, we proposed to reexamine
      certain challenges posed by cognitive remediation and social reintegration (that
      is, deinstitutionalization) of patients with severe and persistent mental
      disorders. METHOD: We reviewed literature on cognition, remediation, smart homes,
      as well as on objects and utilities, using medical and computer science
      electronic library and Internet searches. RESULTS: These technologies provide
      solutions for disabled persons with respect to care delivery, workload reduction,
      and socialization. Examples include home support, video conferencing, remote
      monitoring of medical parameters through sensors, teledetection of critical
      situations (for example, a fall or malaise), measures of daily living activities,
      and help with tasks of daily living. One of the key concepts unifying all these
      technologies is the health-smart home. We present the notion of the health-smart
      home in general and then examine it more specifically in relation to
      schizophrenia. CONCLUSION: Management of people with schizophrenia with cognitive
      deficits who are being rehabilitated in the community can be improved with the
      use of technology; however, such technology has ethical ramifications.

PMID- 15968846
TI  - Quality of life in patients with seasonal affective disorder: summer vs winter
      scores.
AB  - OBJECTIVE: To compare perceived quality of life (QoL) in patients diagnosed with
      seasonal affective disorder (SAD) during the winter and summer months. METHODS:
      Twenty-six patients who were enrolled in an ongoing multicentre study in Canada
      completed 2 measures of QoL (the 20-item Medical Outcomes Study Short-Form
      General Health Survey [SF-20] and the Quality of Life Enjoyment and Satisfaction
      Questionnaire, [Q-LES-Q]) during the winter, when suffering from depression, and
      again during the summer months. RESULTS: Both general and health-related QoL
      scores were significantly improved in patients with SAD during the summer months,
      with scores for the most part falling within normal range. CONCLUSIONS: Perceived
      QoL in patients with SAD is markedly impaired during the winter months but shows
      a substantial rebound during the summer months. The findings of this study
      provide further evidence that SAD is a distinct diagnostic entity.

PMID- 15968847
TI  - Parkinsonism and elevated lactic acid with sertraline.

PMID- 15968848
TI  - Delusion of oral parasitosis in a patient with major depressive disorder.

PMID- 15968849
TI  - Pathological gambling and cross-addiction.

PMID- 15968850
TI  - The psychiatric emergency service patient.

PMID- 15968852
TI  - Taking the low road in Scotland.

PMID- 15968853
TI  - Discrimination not always what it seems?

PMID- 15968854
TI  - Who wants to be a volunteer?--I do.

PMID- 15968855
TI  - The ability of future generations of nurses to support growing numbers of older
      people.

PMID- 15968856
TI  - All but invisible: older gay men and lesbians.

PMID- 15968857
TI  - Using a scoping exercise to guide the development of a care homes learning
      network.
AB  - This article describes a project involving various stakeholders designed to
      develop a learning network for care homes in Bristol and the scoping exercise
      that gave the project team direction.

PMID- 15968858
TI  - Arthritis in the older person: part 1.
AB  - Part 1 of this two-part article identifies the major musculoskeletal disorders
      affecting older people, the signs and symptoms of these disorders and the
      available drug therapies.

PMID- 15968859
TI  - Promoting adequate hydration in older people.

PMID- 15968860
TI  - Overseas nurses' registration.

PMID- 15968861
TI  - Now the work begins.

PMID- 15968862
TI  - Respect and protect.

PMID- 15968863
TI  - Spirituality and Alzheimer's.

PMID- 15968864
TI  - [Somatoform disorders--an update].
AB  - Somatoform disorders occur frequently. The patients complain about numerous
      physical problems and/or pain for which, as a rule, an organic pathological cause
      cannot be not found. They are not willing to or cannot accept psychosomatic
      explanations. The real cause is faulty stress processing due to earlier
      biographical factors, for example, an early attachment disorder. A behavioral
      therapy could help the patient cope with the everyday routine; it influences the
      symptoms and signs, but does not fundamentally change them. Psychodynamic
      approaches are very promising. For comorbidity with anxiety or a depressive
      disorder as well as certain forms of fibromyalgia, psychopharmaceutical drugs
      should be additionally given.

PMID- 15968865
TI  - [Diagnostics and therapy of sleep disorders in the general practice].
AB  - Sleep disorders could be the symptoms of organic or non-organic conditions. The
      diagnostics comprises a detailed medical history of the patient complemented by a
      sleep diary, as well as organic medical and psychological/psychiatric
      examinations. For drug therapy benzodiazepine, antidepressants, neuroleptics,
      antihistamines, plant-based preparations and natural sleep-inducing substances
      such as L-tryptophan or melatonin are used. Nondrug strategies include sleep
      hygiene, stimulus control, sleep restriction and cognitive techniques. For sleep
      disturbances due to a psychological or organic disease, the primary condition
      must be treated.

PMID- 15968866
TI  - [Panic attacks and panic disorder: recognition and treatment].
AB  - To recognize and treat panic attacks or a panic disorder are still an important
      function of the family doctor. For a one-time panic attack, specific counseling
      is normally sufficient. A panic disorder should be treated early with drugs
      and/or with psychotherapy and, in particular, with behavioral therapy. It is also
      recommended that a psychiatric specialist or a neurologist be consulted and to
      coordinate the differential diagnostics and therapeutic procedure with the
      specialist.

PMID- 15968867
TI  - [Headache as a warning symptom].
AB  - Chronic headache is an independent clinical picture. Headaches are to be
      interpreted as a warning sign from the body until this is excluded through
      differential diagnostics. The clarification and the initial treatment should be
      carried out by a neurologist to ensure sufficient diagnostic certainty.

PMID- 15968868
TI  - [Therapy of severe migraine attacks: practical tips].
AB  - Severe migraine attacks are treated with triptans. The forms of administration of
      the active substances depend on the drug profile. A standard therapy does not
      exist. The rate of side effects is low. Triptans are contraindicated for patients
      with coronary, cerebral and peripheral vascular diseases. Under no circumstances
      are they to be combined with ergot alkaloids. Triptans are all the more
      effective, the earlier they are taken. For determining the optimal time point for
      taking the medication, the so-called triptan threshold is helpful. Triptans are
      not suitable for treating status migrainosus. Sumatriptan can be administered
      electively and in compliance with the contraindications for the emergency
      treatment.

PMID- 15968869
TI  - [Diagnosis and therapy of Parkinson's disease].
AB  - The clinical diagnosis of Parkinson's disease is mainly based upon the principal
      symptoms bradykinesia, rigidity and tremor at rest. The differential diagnosis of
      idiopathic Parkinson's disease (IPD) from other parkinsonisms is from the
      prognostic and therapeutic standpoint of considerable importance because the
      Parkinson-Plus syndrome generally does not or only poorly responds to a
      dopaminergic therapy. The treatment of IPD comprises, in addition to,
      dopaminergic medications such as L-dopa or dopamine receptor agonists, operative
      therapeutic options such as deep brain stimulation and nondrug therapies.

PMID- 15968870
TI  - [Puzzling bipolar disorder].
AB  - Despite many advances in making the diagnosis of bipolar disorder, five to twelve
      years lie between the first affective episode and the introduction of an
      effective treatment. However, it is estimated that approximately only one-fourth
      of the patients with bipolar disorder are recognized as such at all. Clinical
      experience plays an important role in the diagnosis. Manias are often the cause
      for the first treatment with drugs, but the daily lives of patients with bipolar
      depression are often clearly more negatively affected. The acute therapy of
      bipolar depression is more complicated than that of mania and the difficult long
      term treatment is always associated with a high suicide risk. A long-term therapy
      of bipolar disorders is not only meaningful for the prevention of new disease
      episodes, but also because it has a positive effect on comorbidities.

PMID- 15968871
TI  - [Neurological diseases and pregnancy: what must the family physician heed?].
AB  - A woman in child-bearing age could principally contract a neurological disease
      during a pregnancy. The diseases are differentiated between those that existed
      before, such as migraines, epilepsy, multiple sclerosis or myasthenia gravis and
      diseases that have an increased incidence during pregnancy, for example stroke,
      thrombosis of a sinus, subarachnoid hemorrhage, restless legs syndrome or
      thoracic outlet syndromes and pregnancy specific diseases. The diagnostics and
      therapy of these diseases are limited by the pregnancy; contraindications must be
      observed.

PMID- 15968873
TI  - [Apoplexy--current status of diagnostics and therapy].
AB  - During the past years increasingly stricter criteria have been applied to the
      primary prevention of ischemic stroke. This applies especially to the treatment
      of asymptomatic carotid stenosis. An operation is indicated for a blockage of 60%
      and higher, including symptom-free patients under 75 years of age. At the moment,
      a final conclusion on the preferred operative procedure--thromboendarterectomy or
      stent implantation--cannot be made. For the secondary prevention of apoplexy, the
      highest relative risk reduction for vascular accidents using thrombocyte
      aggregation inhibitors was achieved with the combination ASA plus dipyridamole.
      Diuretics, calcium antagonists, ACE inhibitors and angiotensin receptor blockers
      (ARB) are equally suitable for the reduction of blood pressure after apoplectic
      insult. Moreover, the latter appear to have advantages for the prevention of a
      renewed apoplexy. The benefit of statins in the secondary prevention of apoplexy
      has been substantiated by the Heart Protection Study. Simvastatin has the best
      evidence for its effectiveness in patients without CHD; in contrast, atorvastatin
      has possibly more benefits for patients with clinically evident CHD. The direct
      thrombin inhibitor, ximelagatran, will be available as an alternative to the oral
      anticoagulant marcumar in the foreseeable future.

PMID- 15968872
TI  - [Restless legs syndrome: therapeutic possibilities in the medical practice].
AB  - The diagnosis of restless legs syndrome is made on the basis of the clinical
      symptoms and, if applicable, complemented with a polysomnography. This is
      followed by neurophysiological examinations and laboratory diagnostics and
      permits a differentiation between idiopathic and secondary RLS. The therapy
      depends upon the form and severity of the disease. For secondary RLS, the primary
      disease must be treated or the symptom-inducing medication must be discontinued.
      An idiopathic RLS is treated with drugs. Primarily, L-dopa/benserazide and
      dopaminergic agonists are used, but opioids and anticonvulsants are also
      successful.

PMID- 15968874
TI  - [Epilepsy and sleep disorders].
AB  - Sleep disorders often occur in patients with epilepsy. Every neurologist is
      familiar with the postictal drowsiness after tonicoclonic convulsions and
      likewise with the provocation of an attack after sleep deprivation that is often
      combined with alcohol consumption. It is more difficult to differentiate between
      motor disturbances and epileptic episodes during sleep. For example, nocturnal
      paroxysmal dystonia, which are frequently an expression of frontal lobe epilepsy,
      are long not recognized as non-epileptic, sleep-associated attacks. In addition,
      nocturnal episodes in context of a REM sleep behavioral disturbance can
      occasionally be differentiated from frontal lobe epileptic seizures only with
      great difficulty. A clear differential diagnostics between epileptic and non
      epileptic attacks during sleep is, however, a requirement for a selective
      treatment.

PMID- 15968875
TI  - [Diagnostics and therapy of depressive symptoms in schizophrenic patients].
AB  - The occurrence of depressive symptoms in schizophrenia is fairly common. In
      contrast to earlier assumptions, they usually have unfavorable consequences on
      the course of the disease. The response of depressive symptoms to therapy is well
      documented by empirical evidence and studies. In reality, however, the treatment
      of depressive symptoms in cases of schizophrenia occurs too rarely. This lack of
      medical treatment is partially explained by the clinicians' apprehension that
      antidepressive therapy could provoke a flare up of the psychosis. Nonetheless,
      this situation is often founded on the incorrect assessment of the depressive
      symptoms as negative symptoms that, in turn, are regarded by many clinicians as
      having limited treatability. In regards to this circumstance, a rethinking is
      desirable and, as a matter of principle, necessary.

PMID- 15968876
TI  - [Diagnostics and therapy of depression in the general practice].
AB  - Depressive disorders are commonly encountered by primary care practitioners. Some
      four million people in Germany suffer from depression. This disease, which is
      life-threatening primarily due to the suicide risk, is still often not recognized
      and, consequently, undertreated. Once diagnosed, depression can be treated
      successfully with antidepressants, cognitive behavior therapy/interpersonal
      psychotherapy or a combination of both. Newer, selective drugs are preferred when
      choosing a suitable antidepressant due to their better tolerability and lower
      toxicity. A synopsis of the diagnosis and therapeutic algorithm of depressive
      disorders as well as recommendations for referrals to a specialist or hospital
      for the primary care physician are provided.

PMID- 15968877
TI  - [Modern therapy for dementia].
AB  - The most frequently diagnosed dementia diseases include Alzheimer disease (AD),
      vascular dementia (VD) and dementia with Lewy bodies. Cholinesterase (ChE)
      inhibitors and the NMDA receptor antagonist memantine are currently recommended
      as first line drugs for the treatment of AD. These anti-dementia drugs have not
      yet been approved for the treatment of VD and DLB although the results of
      controlled clinical studies support the effectiveness of the ChE inhibitors for
      both diseases. The treatment of the primary disease and the secondary prevention
      of cerebrovascular accidents constitute the primary objectives of VD therapy.
      Although single or multiple domain cognitive deficits are the clinical key
      symptoms of dementia, noncognitive psychopathological symptoms (so-called
      behavioral disorders) are particularly common and may even dominate the clinical
      course in the moderate to severe stages. Therefore, it is important to recognize,
      diagnose and specifically treat these additional symptoms. During the last
      decade, the classic neuroleptics and benzodiazepine have been largely replaced by
      modern antidepressants, atypical antipsychotics and benzodiazepine analogues.

PMID- 15968878
TI  - [Evidence-based therapy of painful neuropathies in the primary care practice].
AB  - In the future, a growing number of polyneuropathies is to be expected since
      metabolic diseases are increasing and those falling ill are becoming older. The
      therapy must meet rising standards in the midst of ever tightening financial
      resources. In the process, the treatment must inevitably undergo an assessment
      based on the evidence of its effectiveness. A number of traditional, empirical
      treatment methods will no longer fit into this picture. The therapy of
      neuropathic pain is an example of a fundamental knowledge and cause-oriented
      treatment strategy. Here, a great number of therapeutic options were established
      that comply with the criteria of an evidence-based medicine.

PMID- 15968879
TI  - [Multiple sclerosis: between wish and reality].
AB  - The guidelines for the therapy of multiple sclerosis (MS) are unchanged. An acute
      episode is treated intravenously with high-dosed glucocorticoid. This is usually
      followed by an immunomodulating basic therapy, although the currently approved
      preparations for this purpose are only partially effective. During the last ten
      years, a series of new therapeutic approaches have been developed. The monoclonal
      antibody natalizumab (Tysabri) was approved for use in the U.S.A. in 2004 and
      showed good success, but had to be removed from the market in February 2005
      because of grave side effects. Up until now, the chemokine receptor antagonist
      CCR1 has been tested in a pilot study. A clinical phase III study is being
      planned with MS patients for the interleukin-2 receptor antagonist daclizumab.

PMID- 15968880
TI  - [Management of psychological symptoms and physical symptoms of depression. Rapid
      re-integration of patients into employment].

PMID- 15968881
TI  - [Dual mechanism of action. Remission of physical symptoms].

PMID- 15968882
TI  - P-selectin (CD62p) and P-selectin glycoprotein ligand-1 (PSGL-1) polymorphisms:
      minor phenotypic differences in the formation of platelet-leukocyte aggregates
      and response to clopidogrel.
AB  - INTRODUCTION: Formation of platelet-leukocyte aggregates (PLA) via the CD62p
      ligand PSGL-1 represents an important mechanism by which leukocytes contribute to
      thrombotic and inflammatory events. Deficient variants (namely the Thr715Pro-SNP
      for CD62p and a VNTR-polymorphism for PSGL-1) might affect PLA formation and
      probably the response to clopidogrel (which is known to reduce PLA-formation).
      METHODS: CD62p-expression, PLA-formation and the up-regulation of CD11b before
      (V1) and 24 hours after (V2) a loading dose of clopidogrel 225 mg were
      investigated in ten wild-type controls, ten heterozygote carriers of the
      Thr715Pro-allele and five carriers of the rare PSGL-1 B-allele (2 A/B and 3 B/B).
      RESULTS: CD62p-expression before application of clopidogrel and under clopidogrel
      treatment in Pro715-haplotype samples did not differ from that in wild-type
      subjects. The response to clopidogrel was similar in all subjects. Pro715
      carriers exhibited a significantly lower percentage of monocytes with platelets
      attached prior to clopidogrel treatment (ADP: median 22 (1st-3rd quartile 20-23),
      TRAP: 27 (25 - 38)) compared to the wild-type (ADP: 37 (31-44), TRAP: 55 (37
      63)). These differences were not present under clopidogrel, and CD11b-expression
      was significantly reduced in both groups (controls: median 150 (quartile range
      121 - 230) to 113 (121 - 230), Pro715-carriers: 147 (139 - 221) to 126 (109 -
      170); all values refer to mean fluorescence intensity). Statistical analysis was
      not done in the case of PSGL-1 B-allele carriers, but PLA-formation before and
      under clopidogrel was always at the bottom end of the range seen in the control
      group and the Pro715-carriers or even below this range. CONCLUSION: Minor
      phenotypic differences in the CD62p-PSGL-1 axis could be demonstrated in this
      study. Carriers of these polymorphisms showed a full response to clopidogrel
      comparable to that in control subjects.

PMID- 15968883
TI  - Lack of pharmacokinetic drug-drug interaction between ciclesonide and
      erythromycin.
AB  - OBJECTIVE: To investigate whether systemic exposure to desisobutyrylciclesonide
      (des-CIC) (the pharmacologically active metabolite of ciclesonide) and
      erythromycin are affected by combined administration of ciclesonide and
      erythromycin. METHODS: 18 healthy subjects were enrolled in a Phase 1, open
      label, randomized, three-period crossover study. Each subject received
      ciclesonide (640 microg ex-actuator, equivalent to 800 microg ex-valve, via
      hydrofluoroalkane metered-dose inhaler) and erythromycin (500 mg PO), separately
      and in combination, in random order. Blood samples were collected at timed
      intervals to determine serum concentrations of erythromycin, des-CIC, and
      ciclesonide using HPLC-MS detection. Adverse events were recorded throughout the
      study. RESULTS: Combined administration of ciclesonide and erythromycin did not
      alter the pharmacokinetics (PK) of either drug. The serum concentration vs. time
      profiles of erythromycin, des-CIC, and ciclesonide were similar when ciclesonide
      and erythromycin were administered separately or together. In addition, the PK
      characteristics of erythromycin and des-CIC were equivalent following single or
      co-administration. Point estimates (90% confidence intervals (CI)) for
      erythromycin were as follows: AUC0-inf, 0.96 (0.79, 1.18); Cmax, 1.00 (0.84,
      1.20); and t1/2, 0.96 (0.83, 1.12). The following point estimates (90% CI) were
      obtained for des-CIC: AUC0-inf, 1.16 (1.03, 1.30); Cmax, 1.06 (0.98, 1.15); and
      t1/2, 1.04 (0.96, 1.13). Lack of ciclesonide/erythromycin interaction was
      demonstrated as the 90% CI of AUC0-inf, Cmax, and t1/2 of both compounds were
      entirely within the stipulated equivalence range of 0.67 - 1.50. No study drug
      related adverse events occurred during this study. CONCLUSIONS: Combined
      administration of ciclesonide and erythromycin did not alter the PK properties of
      either drug. Both drugs were safe and well-tolerated. Therefore, systemic
      exposure to ciclesonide or erythromycin is not increased in patients receiving
      concomitant therapy.

PMID- 15968884
TI  - Improved glycemic control with decreased hypoglycemia prevents long-term
      complications in type 2 diabetes patients: long-term simulation analysis using
      the "diabetes mellitus model".
AB  - OBJECTIVE: The purpose of this study was to compare the effect of insulin
      glargine (glargine) and NPH insulin (NPH) on long-term outcomes in type 2
      diabetes patients using the Diabetes Mellitus Model (DMM). METHODS: The DMM
      predicts short- and long-term complications over ten years using data in studies
      published previously. The main effect on outcome is the influence of the
      treatment on the HbA1c level which is simulated over time. The simulation was
      based on a cohort size of 10,000 type 2 diabetes patients taking either glargine
      or NPH. The best scenario, baseline scenario and worst case scenario were
      simulated based on differences of 0.13%, 0.44% and 0.85%, respectively, in HbA1c
      values and corresponding to potentially attainable improvements with comparable
      or lower hypoglycemia rates in glargine-treated patients and NPH-treated
      patients. Assumptions for scenarios 1, 2 and 3 were based on a regression
      analysis of clinical trial data (pooled data clinical trials comparing glargine
      and NPH) in which the effect of glargine on the HbA1c/hypoglycemia incidence
      ratio was superior to that of NPH. RESULTS: The relative risks (RR, glargine/NPH)
      obtained for scenarios 1, 2 and 3 were 0.97, 0.89 and 0.81, respectively, for
      long-term microvascular complications and 0.99, 0.95 and 0.91, respectively, for
      long-term macrovascular complications. RR reductions ranged from 1% in the less
      optimistic scenario to > 20% in the "best case" scenario. Sensitivity analyses
      showed that variations in the mean baseline HbA1c values and duration of the
      diabetes were without effect on these outcomes. CONCLUSIONS: Although there is a
      need to corroborate the results of these simulations with real, long-term
      clinical data, they have demonstrated that, assuming comparable or lower rates of
      hypoglycemia, a better glycemic control (HbA1c reduction) can be expected with
      glargine when compared to NPH together with a reduction in long-term
      complications, mortality and associated costs.

PMID- 15968886
TI  - An evaluation of prescribing errors in primary care in Bahrain.
AB  - OBJECTIVES: Prescribing errors are preventable and are considered an important
      target for improving healthcare. The aim of this study was to identify
      prescribing errors and their determinants in a primary care setting. METHODS:
      Prescriptions with errors were collected on a daily basis by the pharmacy staff
      during the first two weeks of September 2003 in 18 out of 20 primary care health
      centers in Bahrain. Prescribing errors were classified as omission (minor and
      major), commission and integration errors. RESULTS: Out of 77,511 prescriptions
      dispensed, 5,959 (7.7%) were identified to contain errors. The frequency of
      prescribed medication items in 5,959 prescriptions was 16,091. Of these
      medications, 13,630 (84.7%) were with errors and only 13.2% were written using
      generic names. Minor errors of omission such as absence of physician's stamp
      (34.4%), date (9.8%), and information about patients' address (3.8%), age (3.5%)
      and sex (0.5%) were not specified. Major errors of omission accounted for 93.6%
      and were as follows: strength/dose (31.0%), length of therapy/ quantity (29.5%),
      dosage form (19.7%), and frequency of dosing (13.4%). In 6.3% errors of
      commission (incorrect information) the most common was strength/dose (3.3%),
      followed by frequency of dosing (2.6%), dosage form (0.3%), and length of
      therapy/quantity (0.1%). Major errors of omission associated with topical
      preparations were significantly higher than those with systemic preparations.
      However, prescriptions with systemic preparations had a higher rate of commission
      errors. Significant differences in errors were found in prescriptions ordered by
      family physicians and general practitioners. In 9.2% of prescriptions with
      errors, potential drug-drug interactions were expected. CONCLUSIONS: This
      nationwide survey revealed that in primary care, a considerable proportion of
      prescriptions contained errors. Strategies to minimize medication errors by
      improving the prescribing skills, adherence to essential drugs list, and use of
      National Formulary are needed.

PMID- 15968885
TI  - Safety, tolerability and pharmacokinetics of oral S-3304, a novel matrix
      metalloproteinase inhibitor, in single and multiple dose escalation studies in
      healthy volunteers.
AB  - OBJECTIVE: A novel sulfonamide derivative, S-3304, was discovered as a potent
      matrix metalloproteinase (MMP) inhibitor. It is a more specific inhibitor to MMP
      2 and MMP-9 (in vitro) than to MMP-1, and may therefore lack the musculoskeletal
      side effects seen with non-specific inhibitors. The aim of the present study was
      to investigate the safety, tolerability and pharmacokinetics of S-3304 when
      administered as single and multiple oral doses to healthy male volunteers.
      MATERIALS AND METHODS: 48 male volunteers received single oral doses ranging from
      10 - 800 mg S-3304 or placebo under fasting conditions. At the 200 mg dose level,
      effects of high-fat diets were studied in a crossover design. In the multiple
      dose design, 24 male subjects were administered 200 mg, 400 mg or 800 mg S-3304
      or placebo b.i.d. after meals for 10 - 17 days. Studies were conducted in a
      randomized double-blind fashion. Safety assessment was conducted based on blood
      chemistry, hematology, urinalysis, electrocardiogram and physical examination.
      Pharmacokinetic parameters were determined for S-3304 and its metabolites. All
      subjects were enrolled in the studies after obtaining informed consent. RESULTS:
      Adverse events reported after single dose administration of S-3304 or placebo
      were all of mild severity. Adverse events reported in the multiple dose treatment
      with S-3304 or placebo were mostly of mild severity, except for two episodes of
      moderate headache and two episodes of moderate myalgia. Most commonly reported
      adverse events in the multiple treatments with S-3304 were headache and
      somnolence. No clinically significant changes were observed in the clinical
      laboratory tests, except for reversible elevation of alanine aminotransferase of
      one subject at 800 mg S-3304 b.i.d. In the single dose administration, Cmax and
      mean AUC0-infinity linearly increased up to 63,167 ng/ml and 311,960 ng x h/ml at
      the 800 mg dose level, respectively; tmax and t1/2 ranged from 2 - 3 hours and
      from 9.5 - 15.5 hours, respectively. High-fat diets reduced Cmax from 21,565
      ng/ml to 14,095 ng/ml but did not alter AUC0-infinity. Hydroxylated metabolites
      were detected in plasma in concentrations less than 1% of S-3304. Less than 1% S
      3304 was excreted in urine. The AUC of one dosing interval and Cmax did not
      change after multiple doses but t1/2 increased from 9.5 - 10.0 hours to 12.5 -
      13.5 hours. The 6beta-hydroxycortisol/ cortisol ratio was not changed after
      multiple doses suggesting no effect on CYP3A4 activity. CONCLUSION: S-3304
      demonstrated a good safety profile and good systemic exposure when administered
      orally up to 800 mg b.i.d. during 10 - 17 days. At the highest dose level of 800
      mg b.i.d., it was free of rheumatoid arthritis-like symptoms.

PMID- 15968887
TI  - Quality of prescribing for drugs affecting the nervous system: comparison between
      Croatia (Zagreb) and Finland.

PMID- 15968888
TI  - Adult vascular progenitor cells and tissue regeneration in metabolic syndrome.
AB  - Adult vascular progenitor cells (for example endothelial progenitor cells, EPC)
      have been studied for their contribution to vascular repair and angiogenesis.
      These cells can differentiate from bone marrow cells as well as circulating cells
      carrying hematopoetic stem cell markers. In vivo, they take part in
      vasculogenesis in different animal models of limb ischemia, myocardial infarction
      and wound healing. In metabolic disease, the outgrowth and function of EPC in
      vitro is defective and numbers of EPC correlate with classical risk factors of
      cardiovascular disease suggesting a role of EPC in the development of vascular
      complications. Pilot studies for the treatment of myocardial infarction and limb
      ischemia with autologous bone marrow showed a distinct therapeutic benefit that
      is presumably mediated by vasculogenesis in damaged tissues. However, little is
      known about the nature of EPC and their capability to differentiate into
      functional cells for tissue regeneration. In this article, we review and discuss
      the hitherto identified physiological function of EPC, the mechanisms leading to
      dysfunction of these cells and potential therapeutic applications in patients
      with metabolic syndrome or diabetes mellitus and vascular complications.

PMID- 15968889
TI  - Portal vein thrombosis: etiology, diagnostic strategy, therapy and management.
AB  - Myeloproliferative disorder, liver cirrhosis with portal hypertension, deficiency
      of natural anticoagulant proteins, gene mutation and hepatocellular carcinoma are
      the most frequent causes of portal vein thrombosis (PVT). Higher accuracy of the
      diagnostic methods is the reason why today the cause of PVT can be found more
      frequently. With imaging methods, PVT with or without cavernous transformation
      can be diagnosed. Fresh thrombus can be undetected in sonography due to the low
      echogenity but can be recognized in color Doppler sonography, especially with
      contrast-enhancing agent. Contrast-enhanced 3D MR angiography allows a comparable
      accuracy in the detection of PVT as digital subtraction angiography.
      Therapeutical options of PVT consist of mechanical recanalization of the portal
      vein, local fibrinolysis with or without placement of transjugular intrahepatic
      portosystemic stent shunt (TIPS), combination of mechanical recanalization and
      local fibrinolysis, systemic thrombolytic therapy, anticoagulation alone and
      surgical thrombectomy. Once PVT is found in sonography, Doppler sonography may be
      performed in order to distinguish benign from malignant thrombus. If further
      information is needed, MR angiography or contrast enhanced CT is the next step.
      If these tests are unsatisfactory, digital subtraction angiography should be
      performed. Until the early nineties, shunt surgery was recommended in patients
      with PVT who bled despite endoscopic treatment. Today, in symptomatic
      noncavernomatous PVT, recanalization with local methods is recommended.
      Additional implantation of TIPS should be performed when the patient is
      cirrhotic. In recent PVT in non-cirrhotic patients anticoagulation alone is
      recommended. It is expected that in old PVT anticoagulation can prevent further
      extension of the thrombus.

PMID- 15968890
TI  - Microcirculatory and clinical effects of serial percutaneous application of
      carbon dioxide in primary and secondary Raynaud's phenomenon.
AB  - BACKGROUND: A randomized double-blind monocentric trial was conducted at the spa
      of Royat, France, in patients with mild Raynaud's phenomenon (one or two attacks
      a day during the autumn and winter months). Hemodynamic changes were quantified
      by laser Doppler flow (LDF) and computerized chronothermometric test (CT) during
      local application of CO2 and compared with the usual clinical parameters.
      PATIENTS AND METHODS: Patients were randomized to 18 days of CO2 (group 1) or 9
      days of air + 9 days of CO2 (group 2). The gas was applied at a constant
      temperature to previously humidified skin on the forearm. Effects of the active
      treatment were measured by LDF and continuing benefits by computerized
      chronothermometric test (CT test). Clinical assessment was made on four occasions
      (before, in the middle and at the end of treatment, and three months afterwards)
      on the basis of the number of daily attacks and the duration and severity of the
      attacks. RESULTS: LDF showed a significant increase in digital blood flow (+ 41%)
      and in vasomotion (+ 42%) during CO2 treatment but no change on placebo
      treatment. CT test showed a comparable response to cold in the two groups during
      treatment. Three months later, however, warming time was significantly decreased
      (by 7 minutes: 25%) and warming rate increased (+ 22.4%) in group 1 (intergroup
      difference: p = 0.02). There was no difference between groups in the weekly
      number of attacks during treatment periods. In contrast there was a moderate
      increase in both groups in the winter months. There was no increase in the
      severity of the attacks nor in their duration. CONCLUSION: In this clinical
      trial, LDF evidenced positive effects of percutaneous application of natural CO2
      gas on vasomotricity and vasomotion while CT test showed that patients who had
      received 18 days of CO2 adapted more easily to exposure to cold. Clinical
      improvement seems to be masked by winter weather conditions.

PMID- 15968891
TI  - Are there predictors for the outcome of a PGE1 treatment in peripheral arterial
      disease with critical limb ischaemia?
AB  - BACKGROUND: In a multivariate retrospective analysis was conducted to examine
      whether and to what extent PGE1 is therapeutically effective and whether there
      are predictors of response. PATIENTS AND METHODS: The examination included 767
      patients (448 women, 319 men) of a mean age of 71.2 years and with peripheral
      arterial disease (PAD) having existed for 44.7 months on the average. They
      suffered from critical limb ischaemia (Fontaine's stages III/IV) and showed
      average tcpO2 values at the instep of 2 mmHg (0 to 15) and average systolic
      malleolar artery pressures of 18 mmHg (0 to 35 mmHg). Between 1989 and 2001, the
      patients had received treatments in hospital with i.v. PGE1 doses (2x20 microg or
      1x60 microg/day) for an average of 34.2 days (mean of responder- and non
      responder group). Patients were called responders when pain had markedly
      decreased or disappeared, necroses had been reduced or healed completely, and
      vascular reconstruction, PTA or amputations were not necessary. RESULTS: The
      clinical analysis showed 82.4% of the patients to be responders and 17.6% to be
      non-responders. It was demonstrated that the outcome of the therapy was not
      dependent on the supine or sitting tcpO2, the malleolar artery pressure, the
      patient's age or sex, the duration of PAD, the number or kind of concomitant
      diseases, the patient's general condition, the localization and number of
      vascular occlusions, the kind of prior therapy, or the number of previous
      amputations, although differences in some of the parameters, while clinically
      irrelevant, were found to be statistically significant. They are not predictors
      of the outcome of a PGE, therapy. CONCLUSIONS: Even in extremely bad haemodynamic
      situations at the beginning of a therapy (malleolar artery pressures from 0 to 35
      mmHg, tcpO2 0 to 15 mmHg, multilevel occlusive disease, multiple previous
      operations and concomitant diseases), PGE, therapies of more than 20 days - on
      the average 35.6 days (mean of responder group) - duration allow clinically
      relevant positive results to be achieved.

PMID- 15968892
TI  - Determination of amputation level in ischaemic limbs using tcPO2 measurement.
AB  - BACKGROUND: Determination of the optimal amputation level is essential for
      patients, morbidity and rehabilitation. Various non-invasive procedures have been
      proposed to determine the optimal level of amputation. There is no consensus on
      the minimal tcPO2 level that is required to predict the healing of the stump.
      Therefore we aimed to rank the probability of primary wound healing at the most
      distal level and to answer the question if there is a lower limit of tcPO2 below
      which healing cannot occur. PATIENTS AND METHODS: 56 consecutive patients
      undergoing amputation below the knee for ischaemic gangrene of limbs were
      prospectively enrolled in the study. 39 were men (18 of whom were diabetics) and
      17 women (8 diabetics) whose ages ranged from 45 to 87 years (mean 73 years). The
      total of 71 amputations was performed on the 56 patients: 39 below-knee with
      primary healing and, in 16 patients the above-knee reamputation was performed,
      due to the non-healing wound on the below-knee stump. The level of the amputation
      (below or above the knee) was in all cases decided solely on clinical grounds.
      TcPO2 was measured on each patient prior to amputation, on the dorsum of the foot
      and 10 cm below the knee. RESULTS: The median tcPO2 value on the dorsum of the
      foot of diseased legs before amputation was 12 mm Hg (range from 0 to 22 mm Hg).
      At the anticipated level of the amputation of the shank, the median value of
      tcPO2 was 28 mm Hg (8-56 mm Hg). Patients with primary healing of postoperative
      wounds had significantly higher values of tcPO2 than patients with fialure to
      heal (37 mm Hg; range 15-56 mm Hg vs. 18 mm Hg; range 8-36 mm Hg, p < 0.01). The
      success rate increased with higher tcPO2 values at the level of amputation. The
      15% prevalence of reamputations was obtained for tcPO2 values between 25 and 36
      mm Hg (median value 33 mm Hg) and the threshold value of tcPO2 below which the
      stump failed to heal was 15 mm Hg. CONCLUSIONS: Our study showed that tcPO2 is a
      reliable indicator of local ischemia. The integration of this parameter with
      other personal clinical criteria may be a valuable help to the surgeon in
      decision making.

PMID- 15968893
TI  - Evaluation of aortic arch calcification in type 2 diabetic patients.
AB  - BACKGROUND: The purpose of this study is to evaluate the severity of aortic arch
      calcification among type 2 diabetic patients in association with diabetes
      duration, diabetic complications, coronary artery disease and presence of
      cardiovascular risk factors. PATIENTS AND METHODS: This study included 207 type 2
      diabetic patients (101 men) with a mean age of 61.5 +/- 8.1 years and a mean
      diabetes duration of 13.9 +/- 6.4 years. Aortic arch calcification was assessed
      by means of posteroanterior chest X-rays. Severity of calcification was graded as
      follows: grade 0 (no visible calcification), grade 1 (small spots of
      calcification or single thin calcification of the aortic knob), grade 2 (one or
      more areas of thick calcification), grade 3 (circular calcification of the aortic
      knob). RESULTS: Severity of calcification was grade 0 in 84 patients (40.58%),
      grade 1 in 64 patients (30.92%), grade 2 in 43 patients (20.77%) and grade 3 in
      16 patients (7.73%). In simple regression analysis severity of aortic arch
      calcification was associated with age (p = 0.032), duration of diabetes (p =
      0.026), insulin dependence (p = 0.042) and presence of coronary artery disease (p
      = 0.039), hypertension (p = 0.019), dyslipidaemia (p = 0.029), retinopathy (p =
      0.012) and microalbuminuria (p = 0.01). In multiple regression analysis severity
      of aortic arch calcification was associated with age (p = 0.04), duration of
      diabetes (p = 0.032) and presence of hypertension (p = 0.024), dyslipidaemia (p =
      0.031) and coronary artery disease (p = 0.04), while the association with
      retinopathy, microalbuminuria and insulin dependence was no longer significant.
      CONCLUSIONS: Severity of aortic arch calcification is associated with age,
      diabetes duration, diabetic complications (retinopath), microalbuminuria),
      coronary artery disease, insulin dependence, and presence of hypertension and
      dyslipidaemia.

PMID- 15968894
TI  - Importance of early repair of isolated abdominal aortic dissecting aneurysm.
AB  - BACKGROUND: Since the available information on isolated abdominal aortic
      dissecting aneurysm (AADA) is mainly related to case reports or reports of small
      groups of patients, its natural history remains undetermined and there is no
      agreement on its optimal management. The purpose of this study is to define the
      features and pattern of development of this unusual entity as well as to propose
      criteria for treatment based on our own experience and previously published data.
      PATIENTS AND METHODS: We retrospectively evaluated the history of 6 patients
      diagnosed with AADA. The patients were 5 males and 1 female. The mean age was 71
      +/- 8 years (range: 61-80 years), and the mean aneurysm diameter was 54 +/- 14 mm
      (range: 35-70 mm). All of these patients were hypertensive (100%). History of
      cerebrovascular accident, ischemic heart disease, peripheral arterial disease, or
      diabetes mellitus was present in 1 patient, respectively. Two patients developed
      mycotic AADA. RESULTS: Emergency operations had been performed in 3 cases, and
      scheduled surgical reconstruction in the remaining 3 cases. Operation consisted
      of aneurysmectomy and graft replacement of the diseased aortic segment in all
      cases. One patient treated in an emergency setting died subsequently of
      multisystem organ failure, but the others did well. CONCLUSION: Symptomatic
      patients or patients at good risk should undergo surgical repair earlier than in
      the case of abdominal aortic aneurysm without dissection (AAA). Dissection in
      addition to an AAA will further increase the weakness of the aortic wall and the
      possibility of aortic rupture will become higher.

PMID- 15968895
TI  - Does calculation of ankle brachial pressure index need revision?
AB  - Peripheral arterial disease (PAD) is a commonly encountered but a commonly under
      diagnosed condition in clinical practice. Ankle brachial pressure index (ABI) is
      a widely used procedure in its detection. It is also a very good prognostic
      marker not only of PAD but also of mortality. According to the current guidelines
      ABI of a side i.e. either the left or the right, is the quotient of the higher of
      the systolic blood pressures (SBP) of the two ankle arteries of that limb (either
      the anterior tibial artery or the posterior tibial artery) and the higher of the
      two brachial SBP of upper limbs. With the currently existing method of ABI
      calculation, considering only the higher of the SBP of the two ankle arteries, a
      distal stenosis of the ankle arterial system with the lower SBP, may be missed.
      We suggest a modification to the currently existing of calculating ABI. The
      method has been termed by us as the low ankle pressure method. In this method the
      lowest ankle pressure between the two ankle arteries of a particular side is to
      be the numerator and the denominator could be the same as before. A study or a
      series of studies comparing our proposed method with the current one are needed
      to test its clinical utility.

PMID- 15968896
TI  - An unusual presentation of giant cell arteritis.
AB  - A 77-year-old-man with giant cell arteritis who developed bitemporal scalp
      ulcerations is described. Since 1946 when Cooke et al. reported the first case of
      scalp necrosis there were approximately 55 cases published. Scalp ulceration is a
      rare complication of giant cell arteritis and occurs mainly in elderly persons,
      particularly women. About half of all patients were presented to dermatologists.
      Most of the patients (70%) had other serious complications of giant cell
      arteritis: blindness, gangrene of the tongue and nasal septum necrosis. Seventy
      percent of the cases were confirmed by a temporal artery biopsy. The necrosis
      were of varying extent and uni- or bilateral. Although, in most cases necrosis
      has been located bilaterally as in the presented case. Scalp healing was complete
      nearly in all patients by conservative treatment within a year. Scalp ulceration
      is a potentially reversible complication of giant cell arteritis which indicates
      extensive vessel involvement and adequate coricosteroid therapy is required and
      essential.

PMID- 15968897
TI  - [Hypoplasia of the descending thoracic and abdominal aorta in Williams-Beuren
      syndrome].
AB  - Hypoplasia of the descending thoracic and abdominal aorta is a very rare
      condition and its etiology is poorly understood. Associations with congenital and
      acquired disorders have been reported. In this article we present the case of a
      24-year-old woman with hypoplasia of the thoracic and abdominal aorta and
      Williams-Beurensyndrome. This rare syndrome is attributed to deletions of genes
      on chromosome 7, among other the elastin-gene, and is characterized by
      cardiovascular anomalies, dysmorph facial features and mental retardation. The
      patient presented with a history of severe hypertension and recurrent abdominal
      pain since childhood. Diagnosis was established by duplex-sonography and magnetic
      resonance angiography. The patient was treated by an aortoaortic bypass from the
      ascending to the infrarenal aorta with reinsertion of the visceral and the right
      renal arteries. It is essential to recognize the condition early to withhold high
      morbidity and mortality resulting from long standing severe hypertension.

PMID- 15968898
TI  - Celiac artery aneurysm associated with atherosclerotic common hepatic artery
      stenosis.
AB  - Celiac artery aneurysms are rare vascular lesions and represent 4% of all
      splanchnic aneurysms. Media degeneration and atherosclerosis are the most common
      underlying etiologic factors. The risk of rupture and the associated mortality
      rate are 13% and 40% respectively. In contrast, elective repair carries a low
      mortality rate of 5%. Most of celiac artery aneurysms are asymptomatic and in the
      past nearly 80% of the cases were diagnosed when ruptured. Recently, there is an
      increased recognition of all splanchnic aneurysm types, probably because of
      better diagnostic techniques. We report a case of celiac artery aneurysm with
      severe atherosclerotic stenosis of the common hepatic artery. We performed,
      through a midline supraumbilical laparotomy, extended partial aneurysmectomy and
      common hepatic artery ostium endarterectomy. For the closure we used Dacron
      patch. The uncomplicated postoperative patient's course, with no evidence of
      liver dysfunction and excellent patency of the common hepatic artery, suggests
      that this technique offered good results and minimized the perioperative risk.

PMID- 15968899
TI  - Aortic and vena caval reconstruction with retroperitoneal lymph node dissection
      for metastatic germ cell tumor.
AB  - A 49-year-old man who had a huge testicular tumor with retroperitoneal lymph node
      metastasis and bilateral multiple pulmonary metastases was referred to our
      hospital. Firstly orchiectomy was done obtaining the pathological diagnosis of
      mixed type germ cell tumor. After cisplatin-based chemotherapy, he underwent
      resection of the retroperitoneal lymph node involving the abdominal aorta and the
      inferior vena cava. Both great vessels were resected with the tumor and
      reconstructed with prosthetic grafts. Two months after the laparotomy, 12
      metastatic nodules in the left lung were resected. Seven months later, he
      furthermore underwent resection of 4 metastatic nodules in the right lung.
      Microscopically, all resected metastatic tumors were diagnosed to be mature
      teratoma without viable malignant cells. The patient remains well 30 months after
      the first operation. Follow-up CT scan demonstrates patency of aortic and vena
      caval bypass grafts without local recurrence or distant metastasis.

PMID- 15968900
TI  - Pitting edema of the four extremities of rapid appearance.
AB  - We report the case of a 70 year old white man with rapid onset edema of the four
      extremities without any other systemic symptoms. Cardiac failure, nephrotic
      syndrome and hepatic dysfunction were ruled out. Rheumatoid factor was slightly
      elevated at 33 UI/ml and sedimentation rate was within normal range. Ultrasound
      examination of the upper limb revealed increased blood flow (400 ml/min) at the
      level of the brachial artery and edema of the tenosynovial sheaths. A diagnosis
      of remitting seronegative symmetrical synovitis and pitting edema (RS3PE) was
      made and prednisone 15 mg/day was prescribed with rapid disappearance of the
      edema and reduction of the forearm blood flow.

PMID- 15968902
TI  - [Evidence-based medicine and anesthesiology].

PMID- 15968901
TI  - Three cases with May-Thurner syndrome: a possibly under-reported disorder.
AB  - The May-Thurner syndrome is an acquired stenosis of the left common iliac vein
      causing left lower leg edema, thigh discomfort, and deep venous thrombosis. This
      condition was first described by May and Thurner in 1956 in 22% of autopsy
      series. They concluded that it was the underlying factor for deep venous
      thrombosis on the left side. Here, we present three young female patients with
      May-Thurner syndrome, but without actual thrombosis. One of these patients was
      successfully treated with a Wall stent, and the other two patients underwent
      clinical follow-up with anticoagulant therapy.

PMID- 15968903
TI  - [Measurement of cardiac output after cardiac surgery: validation of a partial
      carbon dioxide rebreathing (NICO) system in comparison with continuous
      thermodilution with a pulmonary artery catheter].
AB  - Cardiac output is usually monitored with a pulmonary artery catheter. However,
      because that method is not free of risk, devices have been designed in recent
      years to measure cardiac output in a way that is minimally invasive or fully
      noninvasive. Among such devices is the NICO monitor, which is based on a modified
      Fick equation (partial CO2 rebreathing). OBJECTIVE: To compare the accuracy of
      cardiac output measurements from the NICO monitor to measurements obtained by
      continuous thermodilution with a pulmonary artery catheter. MATERIAL AND METHODS:
      A nonprobabilistic, consecutive sample of 20 patients was enrolled in the early
      postoperative period after elective cardiac surgery (coronary or valve
      procedures) in the recovery ward. Seven measurements of cardiac output were taken
      simultaneously with each method in each patient. RESULTS AND CONCLUSIONS: Cardiac
      output estimated by the partial CO2 rebreathing method was lower than the
      measurement obtained by the pulmonary artery catheter. The percentage error
      between the 2 methods was 37%, indicating that the NICO monitor can not
      substitute for the traditional method. The better correlation found between
      normal-to-low cardiac output values and the absence of side effects of using the
      NICO method suggest that it might be indicated for detecting low cardiac output
      after cardiac surgery, especially when the risk-benefit ratio does not favor
      using a pulmonary artery catheter.

PMID- 15968904
TI  - [Treatment of accidental dural puncture during obstetric epidural analgesia].
AB  - OBJECTIVE: To assess the effectiveness of continuous intrathecal analgesia as
      prophylaxis for postdural puncture headache (PDPH) and for analgesia during labor
      in 12 patients who suffered accidental dural puncture. PATIENTS AND METHODS: A
      total of 920 patients who received spinal analgesia during labor were enrolled.
      Group A (no accidental dural puncture) received a single dose of 10 mL of 0.2%
      ropivacaine, and 5 minutes later continuous epidural infusion of 0.125%
      ropivacaine and 3 micromg mL(-1) was started at a rate of a 5 mL h(-1); a 5 mL
      bolus dose was allowed every 20 minutes if needed. In patients who suffered
      accidental dural puncture (Group B) we inserted an intrathecal catheter to
      administer an initial dose of 3 mL of 0.2% ropivacaine and the same analgesic
      mixture at the same dose as was administered in Group A. Patient characteristics,
      analgesic efficacy, duration of labor and delivery, motor blockade, analgesic
      volume, and incidence of PDPH were recorded. The Student t test was used for
      statistical comparisons. RESULTS: No significant differences in duration of labor
      and delivery, analgesic efficacy, or motor blockade were observed. The incidence
      of PDPH was 16.6% in Group B and 0.33% in Group A. The patients in Group B
      required more additional bolus doses: 10 (SD, 2) in Group B and 3 (1.25) in Group
      A (P<0.01). CONCLUSIONS: Continuous intrathecal analgesia after accidental dural
      puncture was a safe way to provide analgesia during labor and to reduce the
      expected incidence of PDPH.

PMID- 15968905
TI  - [Possibility of cauda equina nerve root damage from lumbar punctures performed
      with 25-gauge Quincke and Whitacre needles].
AB  - OBJECTIVE: To assess the possibility of puncturing nerve roots in the cauda
      equina with spinal needles with different point designs and to quantify the
      number of axons affected. MATERIAL AND METHODS: We performed in vitro punctures
      of human nerve roots taken from 3 fresh cadavers. Twenty punctures were performed
      with 25-gauge Whitacre needles and 40 with 25-gauge Quincke needles; half the
      Quincke needle punctures were carried out with the point perpendicular to the
      root and the other half with the point parallel to it. The samples were studied
      by optical and scanning electron microscopy. The possibility of finding the
      needle orifece inserted inside the nerve was assessed. On a photographic montage,
      we counted the number of axons during a hypothetical nerve puncture. RESULTS:
      Nerve roots used in this study were between 1 and 2.3 mm thick, allowing the
      needle to penetrate the root in the 52 samples studied. The needle orifice was
      never fully located inside the nerve in any of the samples. The numbers of
      myelinized axons affected during nerve punctures 0.2 mm deep were 95, 154, and 81
      for Whitacre needles, Quincke needles with the point held perpendicular, or the
      same needle type held parallel, respectively. During punctures 0.5 mm deep, 472,
      602, and 279 were affected for each puncture group, respectively. The differences
      in all cases were statistically significant. CONCLUSIONS: It is possible to
      achieve intraneural puncture with 25-gauge needles. However, full intraneural
      placement of the orifice of the needle is unlikely. In case of nerve trauma, the
      damage could be greater if puncture is carried out with a Quincke needle with the
      point inserted perpendicular to the nerve root.

PMID- 15968906
TI  - [Anesthesia and cardiac electrophysiology (Part I)].
AB  - Cardiac arrhythmias are a common complication of surgery and anesthesia. They are
      more likely to occur in patients with heart disease and the presence of a
      transitory imbalance can supply the underlying substrate for reentry, triggered
      activity, or abnormal automaticity. The physiologic impact of a given arrhythmia
      depends on its duration, on ventricular response, and on the underlying cardiac
      disease. Optimal management of arrhythmias in the anesthetized patient will
      depend on knowledge of the trigger mechanisms, the effects of anesthetic drugs on
      cardiac electrophysiology, and situations that favor arrhythmias. The
      anesthesiologist must cope with a plethora of problems related to the patient's
      clinical state and the trauma of surgical manipulation. Experience with
      electrocardiography and the application of various devices (pacemakers,
      cardioverters, implantable defibrillators) and knowledge of the pharmacodynamics
      and pharmacokinetics of new intravenous drugs will be essential for patient
      management. The purpose of the present review is to provide the anesthesiologist
      with an overview of current views on the diagnosis and management of arrhythmias
      during anesthesia.

PMID- 15968907
TI  - [Update on the anesthetic management of patients with malignant carcinoid
      syndrome].
AB  - Carcinoid crisis during surgery can lead to severe hemodynamic alterations (hypo-
      and hypertension) and bronchospasm. Intravenous infusion of octreotide, preceded
      by preoperative subcutaneous administration, can allow such crises to be brought
      under control quickly. Given the high prevalence of carcinoid cardiopathy, which
      increases the risk of a crisis in these patients, a preoperative echocardiogram
      should be performed. General anesthesia combined with epidural blockade is
      effective in this context. Block onset should be gradual to avoid the development
      of hypotension, which is difficult to treat. The pharmacodynamic profile of
      remifentanil, its elevated potency, and low histamine releasing potential mean
      that this opioid offers novel advantages during general anesthesia.

PMID- 15968908
TI  - [Anesthesia in intrahepatic cholestasis: Alagille syndrome].
AB  - A 42-year-old patient, diagnosed with Alagille syndrome when he was 1 month old,
      was admitted to the general surgery department to undergo right hepatectomy for
      right lobe carcinoma. Alagille syndrome, also known as biliary duct hypoplasia,
      is an extremely rare genetic condition with multiorganic implications. Liver and
      heart dysfunction will play key roles in the course of the disease and its
      prognosis. An exhaustive preoperative assessment of liver and heart function,
      blood chemistry and the skeleton will be essential for managing these patients.
      This article reviews the main principles underlying the anesthetic management of
      patients with Alagille syndrome.

PMID- 15968909
TI  - [Removal of a pin from an infant's airway: anesthetic technique].

PMID- 15968910
TI  - [On anesthesia for pediatric surgery to treat severe scoliosis].

PMID- 15968911
TI  - [Bleeding associated with septic shock treated successfully with recombinant
      activated factor VII: a case report].

PMID- 15968912
TI  - [Anestesia in a man with hereditary spastic paraparesis].

PMID- 15968913
TI  - What is new in obstetric anesthesia? Lumbar tattoos.

PMID- 15968914
TI  - [Urgent management of the difficult airway outside the hospital: Fastrach or
      ProSeal laryngeal mask?].

PMID- 15968915
TI  - [Critical care of the obstetric patient].

PMID- 15968916
TI  - [Anaphylactic reactions to rocuronium: myth or reality?].

PMID- 15968917
TI  - [Preanesthetic assessment: never lower your guard!].

PMID- 15968918
TI  - Plausibility and verb subeategorization in temporarily ambiguous sentences:
      evidence from self-paced reading.
AB  - A self-paced reading experiment investigated processing of sentences containing a
      noun-phrase that could temporarily be mistaken as the direct-object argument of a
      verb in a subordinate clause but actually constituted the syntactic subject of
      the main clause (often referred to as an early vs. late closure ambiguity).
      Subcategorization preference of the subordinate verb and plausibility of the
      syntactic misanalysis were manipulated Elevated reading times occurred during
      processing of the temporarily ambiguous noun-phrase for those sentences where the
      noun-phrase was an implausible direct-object of the preceding verb, regardless of
      the verbs' subcategorization preferences. Elevated reading times were observed
      for all sentence types following syntactic disambiguation. Subsequent
      correlational analyses showed that the verbs' individual subcategorization
      preferences affected processing time on the critical noun-phrase and the
      syntactically disambiguating main verb.

PMID- 15968919
TI  - Variations in figurative language use as a function of mode of communication.
AB  - Various studies have demonstrated that the mode by which people communicate
      affects the content of their messages. The present study examines the ways in
      which one aspect of language use, namely figurative language, differs as a
      function of mode of communication. Subjects worked together in pairs to build a
      small household appliance, with an "expert" directing a novice in the
      construction. Subjects communicated in one of four modes: full copresence,
      separated by a screen, through an intercom system, or through e-mail. Differences
      between modes were found on a number of measures of figurative language types,
      including what the author has described as "interrogative analogies". These
      differences are discussed in terms of costs, constraints, and affordances
      associated with different media, and the role figurative language plays in
      communication.

PMID- 15968920
TI  - Is literary Arabic a second language for native Arab speakers?: Evidence from
      semantic priming study.
AB  - The mother tongue of the absolute majority of native Arabic speakers is Spoken
      Arabic (SA), which is a local dialect that does not have a written form. For
      reading and writing, as well as for formal communication Literary Arabic (LA) is
      used For the literate Arabs, these two languages are extensively inter-twined in
      every day life. Consequently, it is possible that, despite the difference between
      them, LA is not processed like a regular second language by the cognitive system
      of the native Arabic speakers but rather as an enhancement of the spoken lexicon.
      In the present study we examined this possibility comparing semantic priming
      effects in auditory lexical decision within SA (L1), with the effects found
      across languages with LA or in Hebrew (L2). Hebrew is doubtlessly a second
      language for native Arabic speakers. In this study we have manipulated semantic
      priming In Experiment 1 the targets were in Spoken Arabic and the primes in any
      of the three languages. The semantic priming effect was twice as large within L1
      as between languages and there was no difference between Hebrew and LA. In
      Experiment 2, all primes were in SA whereas the targets were in any of the three
      languages. The priming effects in that experiment were doubled relative to the
      previous experiment, but the inter-language relationships were the same. For both
      language pairings, the semantic priming was larger when the primes were presented
      in SA (and the targets in either Hebrew or LA) than when the primes were
      presented in one of the second languages and the targets in SA. The conclusion is
      that, despite the intensive daily use adult native Arabic speakers make of SA and
      LA, and despite their shared origin, the two languages retain their status as
      first and second languages in the cognitive system.

PMID- 15968921
TI  - Comprehending semantic and grammatical violations in Italian. N400 and P600
      comparison with visual and auditory stimuli.
AB  - Arguments about the existence of language-specific neural systems and
      specifically about the independence of syntactic and semantic processing have
      focused on the event-related brain measures (ERPs) as tool to monitoring moment
      by-moment the cognitive processes underlaid. In the present experiments, the
      available evidence indicates that the ERP response to semantic anomalies is at
      least partially distinct from the ERP response to syntactic anomalies and that
      two distinct processes are activated in sentences comprehension. ERPs were
      recorded from 10 electrodes while subjects read (Experiment 1) or listened
      (Experiment 2) to sentences containing semantic or syntactic violations. Final
      words that were inconsistent with the sentence context elicited a negative-going
      wave at about 400 ms poststimulus, whereas penultimate-word incongruous with the
      grammatical structure (subject-verb non-agreement) elicited a positive-going wave
      about 600ms poststimulus. No differences based on the perceptual modality of the
      stimulus (visual or auditory) nor different ERP correlates as a function of task
      relevance (explicit/implicit task induction) were found The implications of our
      results for Italian language are explained.

PMID- 15968922
TI  - Seeing with new eyes: using positron emission tomography (PET) to identify
      epileptogenic tubers.

PMID- 15968923
TI  - Cognitive dysfunction in children with sleep-disordered breathing.
AB  - Two daily school periods are mandatory in Brazil owing to a shortage of academic
      facilities, which can decrease cognitive performance, especially in children with
      sleep-disordered breathing. This study aimed to verify the influence of starting
      time to school on cognition, comparing children with sleep disorders and normal
      children. Cognition was assessed in 79 children with sleep-disordered breathing,
      468 children with nonrespiratory sleep disorders, and 633 normal control
      children. We analyzed total sleep time, starting time to school (morning or
      afternoon), and grades. First grade morning students with sleep-disordered
      breathing had 8.04 higher odds for cognitive dysfunction than normal children.
      For children with sleep-disordered breathing, second and third grade morning
      students had higher odds for cognitive dysfunction than those who studied in the
      afternoon (3.69 and 4.07). Fourth grade morning students had 8.27 higher odds for
      cognitive dysfunction than first grade children. In conclusion, sleep-disordered
      breathing, grades, and starting time to school interact to affect cognition in
      Brazilian children.

PMID- 15968924
TI  - Clinical and neurophysiologic spectrum associated with atypical absence seizures
      in children with intractable epilepsy.
AB  - The aim of this study was to describe the clinical and neurophysiologic
      correlates of atypical absence seizures in children with intractable epilepsy. In
      a retrospective review, 19 children with videoelectroencephalographic monitoring
      (female n=14; male n=5) fulfilled the electroclinical criteria for this seizure
      type. Atypical absence seizures occurred in a spectrum of clinical conditions
      associated with educational disability and intractable seizures. In comparison
      with children with only atypical absence seizures, children with atypical absence
      in association with multiple seizure types were more likely to have severe
      educational disability (n=11 of 13; P = .01), a slower ictal frequency (n=10 of
      13; P = .01), and slow background rhythms for age (n = 13 of 13; P = .03). This
      study illustrates the broad clinical spectrum in which atypical absence seizures
      are encountered. Differentiation between children with only atypical absence
      seizures and children with multiple seizure types can be useful with respect to
      potential academic ability.

PMID- 15968925
TI  - Applicability of the pediatric evaluation of disability inventory in Slovenia.
AB  - In the process of developmental (re)habilitation, determination of the functional
      abilities of an individual is an important step. For that we need appropriate
      measurement instruments. Because we do not have such measurement instruments in
      Slovenia, we chose the Pediatric Evaluation of Disability Inventory (PEDI),
      translated it, and applied it in daily practice to assess its usefulness and
      applicability. The purpose of the study was to find out whether the functional
      abilities of the population of Slovene children evaluated with the Pediatric
      Evaluation of Disability Inventory is comparable to the American normative data.
      We also wanted to assess the possible influence of gender, parent education,
      community size, and the presence of siblings on children's functional abilities.
      The Pediatric Evaluation of Disability Inventory was administered in the form of
      a structured interview to the parents of 147 healthy children in three age groups
      (0.5-1 year, 3-3.5 years, and 5-5.5 years) in different health care centers in
      Slovenia. Data analysis showed significant differences in functional skills and
      caregiver assistance scale scores when comparing the Slovene sample with the
      American normative data, particularly in the youngest age group. Slovene children
      were found consistently to be different (scoring either higher or lower) from
      American children at comparable ages in several functional skills and caregiver
      assistance scales. The analysis also confirmed the importance of gender and the
      presence of siblings for gaining higher scores on some of the functional skills
      and caregiver assistance scales. The level of parent education did not prove to
      have a significant impact on the results. Our results suggest that the American
      normative data are not completely appropriate for reference purposes in Slovenia.
      The results are in agreement with the findings of other studies, demonstrating
      the importance of ascertaining intercultural differences. We believe that
      adaptation and norming of the Slovene version of the Pediatric Evaluation of
      Disability Inventory are necessary before using the instrument in clinical
      practice in our country.

PMID- 15968926
TI  - Use and value of ordering emergency electroencephalograms and
      videoelectroencephalographic monitoring after business hours in a children's
      hospital: 1-year experience.
AB  - Policies of administration, availability, and utility of ordering emergency
      electroencephalograms (EEGs) during nonbusiness hours vary widely among different
      EEG laboratories. In an attempt to explore further the importance of performing
      such emergency procedures in children, we analyzed the utility of not only
      emergency EEGs but also emergency longterm bedside EEGs and emergency video-EEGs
      at our institution in 1 year. The number of EEG studies performed in 1 year at
      our neurophysiology laboratory was 1821: 1212 routine EEGs, 387 24-hour
      ambulatory EEGs, 81 video-EEGs, and 141 long-term bedside EEGs. The number of
      emergency studies during the same period of time was 32 (1.8% of the total
      studies): 18 emergency EEGs, 8 emergency long-term bedside EEGs, and 6 emergency
      video-EEGs. The reasons for ordering the 18 emergency EEGs included the
      evaluation of (1) altered mental status (n=10), (2) paroxysmal movement
      (including cluster of seizures) (n=6), and (3) prolonged febrile or afebrile
      seizures prior to being discharged on a weekend (n=2). The eight emergency long
      term bedside EEGs were done to evaluate (1) altered mental status (n=6) and (2)
      frequently occurring paroxysmal events (n=2). Four of the eight emergency long
      term bedside EEGs were done after an abnormal emergency EEG. The six emergency
      video-EEGs were done to evaluate frequently occurring paroxysmal events (n=5) and
      altered mental status (n=1). Overall, emergency EEGs and emergency video-EEGs
      were useful in decision making in 30 of 32 (94%) studies. This might be related
      to the fact that a neurologist approved all of the studies. Appropriate
      strategies need to be developed to make this essential service available for
      patient care.

PMID- 15968927
TI  - Epilepsy in chromosomal abnormalities: an Italian sample.
AB  - Epilepsy is common in chromosomal abnormalities, but systematic studies are
      scanty. We describe an Italian sample of patients with chromosomopathies to
      establish epilepsy occurrence and clinical electroencephalographic (EEG)
      features. Forty-five patients with different types of chromosomal abnormalities
      were analyzed to examine different variables in patients with epilepsy (group 1)
      and without (group 2) and to compare the types of epilepsy in our cases with
      respect to a nonselected sample of Italian people with epilepsy. Epilepsy
      occurred in 51.1% (group 1) of cases and prevailed in autosomal abnormalities but
      without a statistical significance (P > .05). There was a prevalence of EEG
      paroxysmal abnormalities in group 1 (P < .0001); continuous spike-waves during
      sleep were observed in three cases. Profound mental retardation prevailed in
      group 1 (P < .001) and mild mental retardation in group 2 (P < .05). Generalized
      epilepsies prevailed significantly (P < .00001). A high-resolution karyotype
      should be undertaken in all patients with epilepsy presenting with mental
      retardation when an obvious etiology is not available.

PMID- 15968928
TI  - Treatment of Sydenham's chorea with intravenous immunoglobulin, plasma exchange,
      or prednisone.
AB  - Sydenham's chorea has been established as a postinfectious autoimmune
      neuropsychiatric disorder. Corticosteroids have been used to treat patients with
      severe disease but are not always effective, and relapses are frequent after
      cessation. Eighteen subjects were entered into this randomized-entry controlled
      trial designed to determine if intravenous immunoglobulin or plasma exchange
      would be superior to prednisone in decreasing the severity of chorea. Mean chorea
      severity for the entire group was significantly lower at the 1-month follow-up
      evaluation (overall 48% improvement). Although the between-group differences were
      not statistically significant, clinical improvements appeared to be more rapid
      and robust in the intravenous immunoglobulin and plasma exchange groups than in
      the prednisone group (mean chorea severity scores decreased by 72% in the
      intravenous immunoglobulin group, 50% in the plasma exchange group, and 29% in
      the prednisone group). Larger studies are required to confirm these clinical
      observations and to determine if these treatments are cost-effective for this
      disorder.

PMID- 15968929
TI  - A child with transient neurologic deficits and headache associated with
      cerebrospinal fluid pleocytosis.
AB  - We report a case of a 10-year-old girl who had several episodes of severe
      headache, altered consciousness, and temporary neurologic signs and symptoms
      within a 2-month period. Cerebrospinal fluid examination showed lymphocytic
      pleocytosis and increased protein. Extensive microbiologic investigation and
      neuroimaging studies were negative. Cerebrospinal fluid findings were normalized
      within a 3-month period, and the patient has not had further episodes through 15
      months of follow-up. This combination of symptoms represents a benign, monophasic
      illness without further progression. The etiology, however, remains unclear.

PMID- 15968930
TI  - Postinfectious myasthenia gravis: report of two children.
AB  - We report two children with transient myasthenia gravis preceded by viral
      illnesses. The first is a 5-year-old boy who developed oculobulbar weakness 2
      weeks following a varicella-zoster infection. The second is a 4-year-old boy who
      developed facial diplegia and dysarthria several weeks following a viral
      pharyngitis. Myasthenia gravis was diagnosed based on the substantial decremental
      changes on 3 Hz repetitive motor nerve stimulation studies for the first child
      and on the positive edrophonium test and complete improvement in symptoms during
      pyridostigmine therapy for both children. In both cases, the symptoms gradually
      resolved and have not recurred following discontinuation of pyridostigmine.
      Molecular mimicry between the acetylcholine receptor and viral proteins might
      provide the nidus for the immune response in this variant of myasthenia gravis.

PMID- 15968931
TI  - A 9-year-old boy with a history of large perinatal stroke, infantile spasms, and
      high academic achievement.
AB  - The prognosis for intellectual development in children with symptomatic infantile
      spasms is usually poor. We report a 9-year-old boy with a history of a large,
      presumed perinatal, left middle cerebral artery infarct discovered when he
      developed infantile spasms at 6 months of age. The infantile spasms responded to
      treatment with adrenocorticotropic hormone. He attained cognitive milestones at
      normal times, requiring only speech therapy for dysarthric speech. At 9 years of
      age, he has seizures and a severe right hemiparesis but is an articulate honor
      roll student in advanced English classes. The development of infantile spasms
      after large-branch middle cerebral artery stroke does not always predict future
      mental retardation.

PMID- 15968932
TI  - Electroencephalography, Doppler vascular scanning, and single photon emission
      computed tomography in a child with hydranencephaly and intractable seizures.
AB  - In a child with hydranencephaly and refractory seizures, the electroencephalogram
      showed a flat isoelectric pattern with no significant slow waves or epileptiform
      activity; cranial computed tomography, magnetic resonance imaging, Doppler
      vascular scanning, and single photon emission computed tomography (SPECT) were
      done to define the pathogenesis of the seizures. The investigations were
      suggestive of a lack of significant cortical, subcortical, or thalamic structures
      with hypoplasia of the vermis and cerebellum. SPECT showed little activity in the
      base of the brain and cerebellum. The cause of the seizures remained unclear in
      spite of the investigations.

PMID- 15968933
TI  - Facial nerve palsy with acute otitis media during the first 2 weeks of life.
AB  - A full-term male newborn presented to us at the age of 2 weeks with left facial
      weakness that had started at the age of 4 days and steadily progressed over a 10
      day period. Physical examination revealed a complete unilateral left peripheral
      facial nerve paralysis, with an erythematous dull and bulging left tympanic
      membrane. Computed tomography and magnetic resonance imaging were normal. The
      patient underwent left myringotomy and placement of a pneumatic equalization tube
      within 24 hours of presentation. He also received a 5-day course of prednisone
      and a 2-week course of antibiotics and acyclovir. Improvement of the facial
      paralysis was rapid, with near-complete resolution at the time of discharge home
      and complete resolution 6 weeks later. To our knowledge, this is the only
      reported case of acute otitis media with associated facial nerve palsy in a
      newborn during the first 2 weeks of life.

PMID- 15968934
TI  - Progressive encephalopathy with edema, hypsarrhythmia, and optic nerve atrophy
      (PEHO)-like syndrome: what diagnostic characteristics are defining?
AB  - Progressive encephalopathy with edema, hypsarrhythmia, and optic nerve atrophy
      (PEHO) syndrome is a rare, apparently autosomal recessive condition in which
      characteristic dysmorphic features are associated with subcutaneous edema, visual
      deficit, early arrest of psychomotor development, seizures, and cerebellar
      atrophy. A condition similar to PEHO syndrome, but without the neuroradiologic or
      ophthalmologic signs, is known as PEHO-like syndrome. We present the case of a
      child with PEHO-like syndrome and underline the need for a careful follow-up of
      these patients to identify signs and symptoms that can have a later onset, such
      as optic atrophy.

PMID- 15968935
TI  - Seizure worsening caused by decreased serum valproate during meropenem therapy.
AB  - Serum concentrations of valproate were reduced and seizures were exacerbated by
      concomitant meropenem therapy in a child with a neurodegenerative disorder and
      epilepsy. In this patient, a rapid decline of valproate serum concentrations was
      observed on two occasions with meropenem antibiotic therapy. This event was the
      most likely cause of observed seizure exacerbation. Meropenem should be used with
      caution in patients treated with valproate owing to the drastic lowering of serum
      valproate concentration and the consequent risk of seizure worsening.

PMID- 15968936
TI  - Anorexia nervosa in a child with tuberous sclerosis complex.
AB  - Psychiatric disorders pose a significant burden to the quality of life of
      individuals with tuberous sclerosis complex and their caregivers. The
      relationship between the location and distribution of brain abnormalities in
      tuberous sclerosis complex and specific neuropsychiatric disorders is largely
      unknown. We present the first case in the literature of a child with tuberous
      sclerosis complex and anorexia nervosa and discuss the relevance of
      electroencephalography, magnetic resonance imaging, and neuropsychologic testing.
      To understand psychiatric disturbances in tuberous sclerosis complex, we must
      consider each of the following factors: cerebral pathology, seizure history,
      cognitive impairment, psychosocial stressors, and medications.

PMID- 15968937
TI  - The right of minors to confidentiality and informed consent.

PMID- 15968938
TI  - Heal the damage: prescription drug consumer advertisements and relative choices.
AB  - The process of choosing and prescribing prescription drugs is complex. While the
      choice about which drug to prescribe is made by the physician, the physician may
      be influenced by patient demand, which, in turn, may be influenced by consumer
      advertisements. As a result, consumer advertisements for prescription drugs need
      to provide information that gives consumers an understanding, not only of drug
      risks and efficacy but also of the notable limits on benefits claimed. This
      Article examines the drug-specific focus of consumer advertising for prescription
      drugs from two perspectives: the need to prevent confusion that could affect
      medical decisions about alternative treatments and the need to prevent
      misimpressions about the value of a drug that can create consumer demand on
      physicians and insurers for more expensive drugs than needed.

PMID- 15968939
TI  - Stark II and physician compensation models: integrating business and legal
      issues.
AB  - In March of 2004, the Centers for Medicare & Medicaid Services released new
      regulations that interpreted the Federal Physician Self Referral Act, otherwise
      known as Stark II. The new regulations, commonly referred to as the Phase II
      regulations, must be carefully considered when structuring physician compensation
      models. Stark II generally holds that physicians may not make a referral for
      designated health services to an entity with which they have a direct or indirect
      financial relationship. This Article outlines the provisions of Stark II that are
      applicable to physician compensation methodologies. In addition, the authors
      evaluate hypothetical transactions involving physician groups seeking viable
      compensation schemes and explore the validity and risks of each.

PMID- 15968940
TI  - Will EMTALA changes leave emergency patients dying on the hospital doorstep?
AB  - Despite charges that it is at times ambiguous and overly burdensome, the
      Emergency Medical Treatment and Labor Act (EMTALA) remains an important
      protection for patients, and a valuable instrument for enforcing public policy
      goals in the area of emergency healthcare services. The 250 Yard Rule is a small
      but crucial part of EMTALA, extending the statute's protections to emergency
      patients who have narrowly failed to reach the hospital's entrance. Following
      recent revisions to EMTALA's implementing regulations, some health-care law
      practitioners and senior federal regulators have opined that enforcement of the
      250 Yard Rule will be dramatically curtailed. This Article explores the legal and
      public policy origins of the 250 Yard Rule and their continuing applicability in
      the current regulatory environment. The Article concludes that the regulatory
      basis for the 250 Yard Rule remains intact and that the legislative intent behind
      EMTALA, as well as ongoing public policy goals, dictate that the 250 Yard Rule be
      preserved.

PMID- 15968941
TI  - Expanding the scope of fiduciary duties to fill a gap in the law: the role of
      nonprofit hospital directors to ensure patient safety.
AB  - In the wake of the patient safety movement, there is a glaring disconnect between
      the increasing responsibilities placed on hospital board members and the limited
      accountability for those board members if they fail to meet their
      responsibilities. This Article discusses how the effectiveness of new patient
      safety laws is diminished by the lack of accountability of nonprofit board
      members. The Article suggests that an expanded notion of corporatefiduciary
      duties, enhanced by shifts in social norms, would contribute to patient safety
      reform.

PMID- 15968942
TI  - I want my information back: evidentiary privilege following the partial birth
      abortion cases.
AB  - In February 2004, privacy concerns captured the public's attention when the
      United States government, the defendant in a lawsuit challenging the
      constitutionality of the Partial-Birth Abortion Ban Act of 2003, sought to
      subpoena the medical records of patients receiving intact dilation and extraction
      (also known as "partial birth") abortions in six different hospitals and six
      Planned Parenthood centers across the country. Three different federal court
      cases explored the enforceability of the subpoenas. This Note explores the
      rationales used by the three courts in examining the privacy interests involved.
      It then suggests some possible solutions for systematically protecting medical
      information: a legal solution; a technological solution; and a combination of
      both. The legal solution involves creating a federal physician-patient privilege,
      similar to that enforced in many states and parallel to the federal
      psychotherapist-patient privilege. The technological solution requires the
      complicity of multiple jurisdictions to verify the necessity of revealing medical
      information. Taken together, these solutions can assist the government in
      protecting its citizens by imposing more checks on itself.

PMID- 15968943
TI  - Sample excess benefit tax opinion.

PMID- 15968944
TI  - Major factors in the controversy of pulsatile versus nonpulsatile flow during
      acute and chronic cardiac support.

PMID- 15968945
TI  - Three-dimensional numeric simulation of flow through an aortic bileaflet valve in
      a realistic model of aortic root.
AB  - A three-dimensional, realistic model of an aortic mechanical heart valve and
      Valsalva sinuses was developed to predict, by means of a numerical time dependent
      simulation, the flow field during a fraction of the systolic period. The numeric
      simulation was performed upon a model of valve similar to a Carbomedics 27 mm
      placed in a physiologic aortic root shaped model, in which no symmetry planes
      were exploited to reach a more realistic level. Input data for the simulation
      have been acquired during an experimental session on the same valve, according to
      the guidelines of testing protocol for prosthetic heart valves. Flow was assumed
      to be Newtonian and laminar at low regime and the leaflets fixed in the fully
      open position. The forward flow of the systolic phase was investigated, and a
      comparison with experimental results was performed at peak systole, the most
      representative point of the cardiac cycle. The results of this simulation
      furnished a reasonable indication (in terms of fluid dynamics) parameters
      downstream of the prosthetic device, especially in Valsalva sinuses, the role of
      which is proven to affect the valve's performance.

PMID- 15968946
TI  - Heat and mass transfer during the cryopreservation of a bioartificial liver
      device: a computational model.
AB  - Bioartificial liver devices (BALs) have proven to be an effective bridge to
      transplantation for cases of acute liver failure. Enabling the long-term storage
      of these devices using a method such as cryopreservation will ensure their easy
      off the shelf availability. To date, cryopreservation of liver cells has been
      attempted for both single cells and sandwich cultures. This study presents the
      potential of using computational modeling to help develop a cryopreservation
      protocol for storing the three dimensional BAL: Hepatassist. The focus is upon
      determining the thermal and concentration profiles as the BAL is cooled from 37
      degrees C-100 degrees C, and is completed in two steps: a cryoprotectant loading
      step and a phase change step. The results indicate that, for the loading step,
      mass transfer controls the duration of the protocol, whereas for the phase change
      step, when mass transfer is assumed negligible, the latent heat released during
      freezing is the control factor. The cryoprotocol that is ultimately proposed
      considers time, cooling rate, and the temperature gradients that the cellular
      space is exposed to during cooling. To our knowledge, this study is the first
      reported effort toward designing an effective protocol for the cryopreservation
      of a three-dimensional BAL device.

PMID- 15968947
TI  - Mechanical fragility calibration of red blood cells.
AB  - Mechanical fragility of red blood cells (RBCs) is a critical variable for the
      hemolysis testing of many important clinical devices, such as pumps, valves, and
      cannulae, and gas exchange devices. Unfortunately, no standardized test for RBC
      mechanical fragility is currently well accepted. Although many test devices have
      been proposed for the study of mechanical fragility of RBCs, no one has ever
      shown that their results have any relevance to a blood pump. Therefore, the
      fundamental objective of this study was to determine if one or more test devices
      could be validated as calibrators to document the fragility of the test blood
      used for any particular test blood. We compared five mechanical fragility test
      systems to each other and to a Biopump, with respect to hemolysis. All five
      devices seem to measure the same parameter; the hemoresistometer most closely
      matched the pump test results, but the stainless steel bead test may be the most
      practical for routine calibration purposes.

PMID- 15968948
TI  - Evaluation of computational models for hemolysis estimation.
AB  - The potential for mechanical erythrocyte damage, or hemolysis, in heart valves
      and blood pumps has been estimated using computational fluid dynamics (CFD)
      analysis, combined with mathematical models of red cell damage mechanisms. To
      date, these prediction approaches have not been compared with each other in
      common benchmark cases, nor have they been evaluated in radically different flow
      geometries. In this study, four test devices, including a hemoresistometer, a
      spinning disk, a capillary tube, and a concentric cylinder viscometer were
      hemolysis tested and computationally simulated. A number of existing models were
      used to predict blood damage and these models were compared with each other and
      with actual measurement of hemolysis. The study indicates that the effectiveness
      of blood damage prediction from the existing models is similar and can
      potentially be improved with the consideration of a proposed repeated flow
      passage effect. It also indicates that the improved models can be used to more
      effectively predict blood damage in widely different situations.

PMID- 15968949
TI  - Mechanisms of mechanical heart valve cavitation in an electrohydraulic total
      artificial heart.
AB  - Until now, we have estimated cavitation for mechanical heart valves (MHV) mounted
      in an electrohydraulic total artificial heart (EHTAH) with tap water as a working
      fluid. However, tap water at room temperature is not a proper substitute for
      blood at 37 degrees C. We therefore investigated MHV cavitation using a glycerin
      solution that was identical in viscosity and vapor pressure to blood at body
      temperature. In this study, six different kinds of monoleaflet and bileaflet
      valves were mounted in the mitral position in an EHTAH, and we investigated the
      mechanisms for MHV cavitation. The valve closing velocity, pressure drop
      measurements, and a high-speed video camera were used to investigate the
      mechanism for MHV cavitation and to select the best MHV for our EHTAH. The
      closing velocity of the bileaflet valves was slower than that of the monoleaflet
      valves. Cavitation bubbles were concentrated on the edge of the valve stop and
      along the leaflet tip. It was established that squeeze flow holds the key to MHV
      cavitation in our study. Cavitation intensity increased with an increase in the
      valve closing velocity and the valve stop area. With regard to squeeze flow, the
      Bjork-Shiley valve, because it is associated with slow squeeze flow, and the
      bileaflet valve with low valve closing velocity and small valve stop areas are
      better able to prevent blood cell damage than the monoleaflet valves.

PMID- 15968951
TI  - Total heart replacement with dual centrifugal ventricular assist devices.
AB  - In an ovine feasibility study, we implanted two HeartMate-III centrifugal
      ventricular assist devices (VADs) for total heart replacement. With
      cardiopulmonary bypass support, both ventricles were transected at the
      atrioventricular groove, preserving a rim of ventricular tissue. The
      atrioventricular valves were excised, and the aorta and pulmonary artery were
      transected above the ventriculoarterial valves. An interatrial septal window was
      created by excising the foramen ovale. The VADs' sewing rings were attached to
      the left and right ventricular remnants, respectively. Outflow grafts were
      anastomosed to the aorta and pulmonary artery. The left VAD operated continuously
      at 4,500 rpm. Right VAD speed increased from 2,000 to 4,500 rpm in 500 rpm
      increments. Outflow graft flow, pressure, oxygen saturation, and shunt direction
      were recorded. The pulmonary artery to aortic ratio of flow and pressure
      increased from 0.26 and 0.15 (at 2,000 rpm) to 1.21 and 0.53, respectively (at
      4,500 rpm). The interatrial shunt, which was right to left at lower right VAD
      speeds, progressed to bidirectional, then to left dominant as right VAD speed
      increased. Outflow-graft oxygen saturation was reflective of the shunt direction.
      In this acute experiment, total heart replacement with continuous flow VADs
      satisfactorily balanced left and right ventricular flows and preserved the
      physiologic circulatory response.

PMID- 15968950
TI  - Durability testing of a completely implantable electric total artificial heart.
AB  - In vitro durability testing was conducted on the Penn State/3M electric total
      artificial heart (ETAH) to determine device durability and to evaluate device
      failures. A specialized mock circulatory loop was developed for this testing.
      Customized software continuously acquired data during the test period, and
      failures were analyzed using FMEA (failure modes and effects analysis) and FMECA
      (failure modes, effects, and criticality analysis) principles. Redesigns were
      implemented when appropriate. Reliability growth principles were then applied to
      calculate the 1 and 2 year reliability. The 1 and 2 year reliability of the Penn
      State/3M ETAH was shown to be 96.1% and 59.9%, respectively, at 80% confidence.

PMID- 15968952
TI  - Loss of catheter locking solution caused by fluid density.
AB  - The avoidance of clotting in catheter lumina between treatments usually entails
      locking with an anticoagulant solution such as heparin. In a previous work, it
      was shown that approximately 20% of locking solution flows from the catheter
      during instillation of the lock equal in volume to the lumen volume. Furthermore,
      the locking solution may spill into the blood stream under the influence of
      gravity. This work investigates the influence of density and viscosity of the
      locking solution on the volume and speed of locking solution loss from the
      catheter lumen. A large fraction of the catheter locking solution spills under
      the influence of gravity if the locking solution's density is higher than the
      fluid it spills to (blood). Locking solution lost is replaced by blood. Viscosity
      delays this process, but at 90 minutes after injection, the loss is completed
      even when highly viscous lock solutions are used. Slow administration of the lock
      has negligible influence upon the dynamics of the loss.

PMID- 15968953
TI  - Quotidian nocturnal hemodialysis improves cytokine profile and enhances
      erythropoietin responsiveness.
AB  - Inflammation is implicated in the pathogenesis of erythropoietin (EPO) resistance
      in patients with end-stage renal disease. Interleukin (IL)-6 and tumor necrosis
      factor (TNF)-alpha are suggested to suppress erythropoiesis in uremia. Insulin
      like growth factor (IGF)-1 has been proposed to stimulate erythropoiesis.
      Nocturnal hemodialysis (NHD) has been demonstrated to improve anemia management
      with enhanced EPO responsiveness without altering survival of red blood cells. We
      tested the hypothesis that augmentation of uremia clearance by NHD results in a
      reduction of proinflammatory cytokine levels, thereby enhancing EPO
      responsiveness. Using a cross-sectional study design, 14 prevalent patients on
      NHD and 14 patients on conventional hemodialysis (CHD) matched for age and
      comorbidities and controlled for hemoglobin concentrations and iron status were
      studied. Outcome variables included EPO requirement and plasma levels of EPO,
      parathyroid hormone, C reactive protein, IL-6, TNF-alpha, and IGF-1. The primary
      outcome was to determine the between group differences in (1) cytokine profile
      and (2) EPO requirement. The secondary outcome was to examine the potential
      correlation between cytokine levels and EPO requirement. There were no
      significant differences in patient characteristics, comorbidities, hemoglobin,
      iron indices, and parathyroid hormone levels between the two cohorts. EPO
      requirement was significantly lower in the NHD cohort [90.5 +/- 22.1 U/kg/ week
      (NHD) vs. 167.2 +/- 25.4 U/kg/week (CHD), p = 0.04]. Plasma IL-6 levels were
      lower in the NHD cohort [3.9 +/- 0.7 pg/ml (NHD) vs. 6.5 +/- 0.8 pg/ml (CHD), p =
      0.04]. C reactive protein tended to decrease [4.59 +/- 1.34 (NHD) vs. 8.43 +/-
      1.83 mg/L (CHD), p = 0.14]. TNF-alpha, and IGF-1 levels did not differ between
      the two groups. Direct associations were found between EPO requirement and C
      reactive protein levels (R = 0.62, p = 0.001), and IL-6 levels (R = 0.57, p =
      0.002). Augmentation of uremic clearance by NHD improves EPO responsiveness in
      end-stage renal disease. A possible mechanism for this improvement is through
      better control of inflammation, as manifested by lowering of plasma IL-6 levels.
      Further studies are required to clarify the mechanisms by which NHD decreases
      inflammation.

PMID- 15968954
TI  - Low dose intradermal versus high dose intramuscular hepatitis B vaccination in
      patients on chronic hemodialysis.
AB  - Patients with end-stage renal disease on hemodialysis (HD) are at high risk for
      hepatitis B infection. We randomly assigned 86 new patients on HD to receive
      either 40 microg intramuscular (group 1) or 20 microg intradermal (group 2)
      recombinant hepatitis B vaccine, in three doses at 0, 1, and 4 months. All
      patients were seronegative at baseline for hepatitis B surface antigen (HBs-Ag),
      hepatitis B surface antibody (HBs-Ab), and hepatitis B core antibody (HBc-Ab).
      HBs-Ab seroconversion rate and antibody titer (ELISA assay) were compared in 27
      patients of group 1 and 35 patients of group 2 at 1 month, and in 20 patients of
      group 1 and 26 patients of group 2 at 6 months after the last vaccine dose. The
      seroconversion rates (HBs-Ab titer >10 IU/L) were 55.6% and 50% in group 1, and
      54.3% and 50% in group 2, at 1 and 6 months, respectively (p = NS). Patients'
      age, body mass index, serum albumin concentration, and sex distribution were
      similar in the responders and nonresponders. Intradermal hepatitis B vaccination
      used at half dose may be a cost saving alternative to intramuscular vaccination
      in patients on HD. However, the low overall seroconversion rate mandates seeking
      alternative ways of vaccination in this patient population.

PMID- 15968955
TI  - Diffusive-convective mass transfer rates for solutes present on both sides of a
      dialyzer membrane.
AB  - The transport (J) of waste products across dialyzer membranes is known to be
      proportional to the blood inlet concentration (Cbi) according to J = KCbi, where
      K is the clearance. For solutes present on both sides of the membrane, like
      sodium chloride, it has been shown that under certain conditions the transport
      rate will depend linearly also upon the dialysis fluid inlet concentration Cdi
      according to J = KbCbi -KdCdi. Kb and Kd are generalized clearances, which depend
      upon flow rates and membrane permeability but are independent of the
      concentrations. We have extended the results of Ross et al. in three ways. First,
      they only considered ultrafiltration (UF) that is equally distributed along the
      dialyzer. This is an unrealistic assumption, especially in hemodiafiltration and
      hemofiltration treatments with large UF rates (Quf) leading to large pressure
      drops along the dialyzer. Our approach allows for an arbitrary UF distribution.
      Second, it was possible to incorporate the more realistic model of Villaroel et
      al. for the local combination of diffusion and convection. Finally, we allow an
      arbitrary distribution of blood among the different fibers. All of these results
      are valid in both cocurrent and countercurrent configurations. With a sieving
      coefficient of 1, a good approximation for small solutes, we were also able to
      show that Kd = Kb - Quf, irrespective of the UF distribution along the dialyzer.
      This is an important result that, for example, provides a theoretical foundation
      for allowing a nonzero Quf in conductivity based clearance measurements.

PMID- 15968956
TI  - Development of the human umbilical vein scaffold for cardiovascular tissue
      engineering applications.
AB  - Biologic function and the mechanical performance of vascular grafting materials
      are important predictors of graft patency. As such, "functional" materials that
      improve biologic integration and function have become increasingly sought after.
      An important alternative to synthetic materials is the use of biomaterials
      derived from ex vivo tissues that retain significant biologic and mechanical
      function. Unfortunately, inconsistent mechanical properties that result from
      tedious, time consuming, manual dissection methods have reduced the potential
      usefulness of many of these materials. We describe the preparation of the human
      umbilical vein (HUV) for use as an acellular, three-dimensional, vascular
      scaffold using a novel, automated dissection methodology. The goal of this
      investigation was to determine the effectiveness of the autodissection
      methodology to yield an ex vivo biomaterial with improved uniformity and reduced
      variance. Mechanical properties, including burst pressure, compliance, uniaxial
      tension testing, and suture holding capacity, were assessed to determine the
      suitability of the HUV scaffold for vascular tissue engineering applications. The
      automated methodology results in a tubular scaffold with significantly reduced
      sample to sample variation, requiring significantly less time to excise the vein
      from the umbilical cord than manual dissection methods. Short-term analysis of
      the interactions between primary human vascular smooth muscle cells and
      fibroblasts HUV scaffold have shown an excellent potential for cellular
      integration by native cellular remodeling processes. Our work has shown that the
      HUV scaffold is mechanically sound, uniform, and maintains its biphasic stress
      strain relationship throughout tissue processing. By maintaining the mechanical
      properties of the native blood vessels, in concert with promising cellular
      interactions, the HUV scaffold may lead to improved grafts for vascular
      reconstructive surgeries.

PMID- 15968957
TI  - Establishment of highly differentiated immortalized human hepatocyte line with
      simian virus 40 large tumor antigen for liver based cell therapy.
AB  - Acute liver failure and metabolic liver disorder animal models have demonstrated
      that hepatocytes transplanted into the liver or spleen survive and participate in
      the liver repopulation process, and recent studies have documented the usefulness
      of hepatocyte transplantation in humans. However, despite the promising cell
      therapy, there are still many restrictions, such as the shortage of donor human
      livers and the limited lifespan and the functional insufficiency of primary
      cultured hepatocytes. The immortalized and highly differentiated human hepatocyte
      could provide an unlimited supply of transplantable cells. In this study, we
      established an efficient and highly differentiated immortalized human hepatocyte
      line for bioartificial liver and hepatocyte transplantation research. Hepatocytes
      isolated from the liver of a 25 year old, brain dead male were transfected with
      pcDNA3.1 (-) recombinant plasmid containing the genes encoding simian virus 40
      (SV40) large tumor antigen. One of the hepatocyte clones, HepLL, displayed highly
      differentiated liver functions with immortalized characteristics and was selected
      with a 700-300 microg/ml of G418 technique in 42 days. To characterize this
      immortalized cell line for cell therapy in the near future, HepLL cells were
      studied with immunohistochemistry, reverse transcription-polymerase chain
      reactions, immunoblotting, and tumorigenicity tests. The results revealed that
      HepLL cells displayed morphologic characteristics of liver parenchymal cells,
      secreted albumin, synthesized urea and glycogen, and expressed liver enriched
      functional markers, but there were no tumorigenic qualities after transplantation
      into severe combined immunodeficiency mice. Thus this immortalized human
      hepatocyte line is expected to be a useful tool for studying the functions of
      differentiated human hepatocyte and a promising strategy to resolve the shortages
      of donor organs and the limits of primary human hepatocyte for transplantation
      and bioartificial liver support systems.

PMID- 15968958
TI  - Simulated blood transport of low density lipoproteins in a three-dimensional and
      permeable T-junction.
AB  - Previous studies indicate that blood flow and transport of macromolecules in the
      cardiovascular system and tissues are essential to understand the genesis and
      progression of arterial diseases and for the effective implementation of arterial
      grafts, as well as to devise efficient drug delivery mechanisms. In the present
      study, we use computational fluid dynamics to simulate the blood flow and
      transport of low-density lipoproteins (LDL) in a three-dimensional and permeable
      T junction. The Navier-Stokes equation, Darcy's Law, and the advective diffusion
      equations are the mathematical models used to simulate the flow and transport
      phenomena of the system. In the numeric model to implement the finite volume
      method, we used the computational fluid dynamics software Fluent 6.1. The
      simulation shows higher LDL concentration in the luminal surface at the junction
      under physiologic flow conditions. At 1 mm depth into the artery from the luminal
      surface, the LDL concentration is approximately 40% of the lumenal concentration,
      and at 2 mm depth, it reduces to 20%. Ultimately, the concentration drops further
      and reaches zero at the outer wall boundary.

PMID- 15968959
TI  - Quantitative changes in mast cell populations after left ventricular assist
      device implantation.
AB  - Mast cells have been implicated as important in tissue remodeling and fibrosis.
      We investigated the effect of mechanical ventricular unloading upon myocardial
      fibrosis and cardiac mast cell density in patients undergoing left ventricular
      assist device (LVAD) implantation. Paired myocardial tissue samples were obtained
      from 30 patients with end-stage cardiomyopathy at the time of LVAD implantation
      and at the time of removal and were compared with samples taken from donor
      hearts. Tissue sections were stained and quantitated for mast cells and
      myocardial fibrosis. Mast cell density (tryptase positive cells) in
      cardiomyopathy was higher than that in donor hearts (33.5 +/- 3.6 SEM cells/10
      fields vs.15.2 +/- 2.0 SEM cells/10 fields respectively, p = 0.04) and was lower
      than LVAD supported hearts (33.5 +/- 3.6 SEM cells/10 fields vs. 49.8 +/- 5.7 SEM
      cells/10 fields respectively, p = 0.01). Mast cells are primarily localized in
      areas of increased interstitial fibrosis adjacent to myocardial cells and not
      vessels. There was statistically significant correlation between mast cells and
      interstitial collagen (p = 0.03) in patients before LVAD implantation that did
      not persist after mechanical support (p = 0.18). These results suggest that
      mechanical support with left ventricular assist devices induces an increase in
      mast cell number in the myocardium and an associated decrease in myocardial
      fibrosis. We believe these data demonstrate a dual role for cardiac mast cells in
      the increase in fibrosis in heart failure and the decrease after LVAD and its
      associated cardiac improvement.

PMID- 15968960
TI  - Poly-methyl pentene oxygenators have improved gas exchange capability and reduced
      transfusion requirements in adult extracorporeal membrane oxygenation.
AB  - The performance of poly-methyl pentene (PMP) oxygenators (Medos Hilite 7000LT)
      was compared with that of silicone membrane (SM) oxygenators (Medtronic 1-4500
      2A) for adult extracorporeal membrane oxygenation (ECMO). Forty consecutive
      patients were selected retrospectively pre- and post-introduction of PMP
      oxygenators. They were selected according to the dates they received ECMO and
      were separated into two equal groups with similar backgrounds. The flow path
      resistance, gas and heat exchange efficiency, consumption of coagulation factors
      and platelets, blood transfusion requirements, and incidence of clots for each
      oxygenator type was assessed. Adult PMP oxygenators showed lower blood path
      resistance than SM oxygenators. However, lower consumption of blood products in
      these oxygenators was a direct result of their smaller surface area and heparin
      coated design, reducing contact activation of coagulation factors. These
      oxygenators are noticeably smaller, require lower priming volumes, and have
      better gas exchange capability than SM oxygenators. They showed greater stability
      and preservation of coagulation factors and platelets compared with SM
      oxygenators. They also had the advantage of a functioning integrated heat
      exchanger. Using a single PMP oxygenator in the first instance may be adequate
      for the majority of patients and would significantly reduce red blood cell
      consumption during ECMO.

PMID- 15968962
TI  - Basic principles of the intraaortic balloon pump and mechanisms affecting its
      performance.
AB  - The intraaortic balloon pump (IABP) is the single most effective and widely used
      device for temporary mechanical assistance of the failing heart. Although the
      principles underlying IABP function are simple, various biologic factors often
      determine its performance in a particularly complicated way. We briefly describe
      the basic disciplines of counterpulsation by IABP and the induced hemodynamic
      changes while clarifying the biologic mechanisms that play a crucial role in the
      modification of IABP acute hemodynamic performance.

PMID- 15968961
TI  - Effects of nutrient and hemoglobin enriched cell free perfusates upon ex vivo
      isolated rat heart preparation.
AB  - We evaluated the effects of nutrient enriched medium and hemoglobin based oxygen
      carrier (HBOC) upon myocardial functional recovery after 15 minutes of warm
      ischemia in an isovolumic Langendorff rat heart model. Hearts (n = 8/group) were
      perfused at constant pressure (90 mm Hg) with Krebs-Henseleit buffer or HEPES
      modified cell culture medium (M199) in the absence and presence of HBOC. Hearts
      received 15 minutes of normothermic no flow ischemia followed by 60 minutes
      reperfusion. Hemodynamics, coronary flow, and tissue water content were measured,
      and microscopic evidence of injury including TUNEL assay was assessed.
      Preischemic left ventricular performance (left ventricular developed pressure and
      maximum rate of positive and negative change in systolic pressure) and coronary
      flow were similar among groups. At 60 minutes of reperfusion, M199 alone provided
      more stable and complete left ventricular systolic and diastolic functional
      recovery than any other perfusate. Coronary flow rates reflected left ventricular
      function observed under each perfusate condition. TUNEL assay showed arterial
      endothelial cell death in some hearts perfused with HBOC. Tissue water content
      did not reflect functional recovery. The combination of M199 and HBOC was
      associated with poor recovery and elevated perfusate methemoglobin. In this
      system, postischemic dysfunction is prevented by components in M199. Added HBOC
      does not improve functional recovery and negates the salutary effects of M199,
      possibly by augmenting methemoglobin formation.

PMID- 15968963
TI  - RE: Heng BC, Tong c: the differentiation status of stem cells and their
      derivatives: A key consideration in transplantation medicine. ASAIO J 50: 626
      627, 2004.

PMID- 15968964
TI  - Part 1: principles of research on pulsatile and nonpulsatile perfusion during
      chronic support.

PMID- 15968965
TI  - Kolff and Kampen.

PMID- 15968966
TI  - Shaping biomedical research priorities: the case of the National Institutes of
      Health.
AB  - Despite the international interest in priority setting as an important tool for
      health policy, there has been comparatively little interest in the setting of
      research priorities. One of the few places where there has been such an interest
      is at the National Institutes of Health (NIH) in the United States. Under
      pressure from Congress to explain its priority setting process, the NIH has tried
      to explain the criteria and process it uses. The NIH procedure is described, and
      the problems created by the criteria it uses are analyzed. Although it uses the
      language of priority setting, it is uncertain whether it does have a real method
      of setting priorities. Nonetheless, despite the lack of a method, the results of
      its work are lauded. In the long run, however, NIH will need a more rigorous
      method of setting priorities.

PMID- 15968967
TI  - Can medical criteria settle priority-setting debates? The need for ethical
      analysis.
AB  - Medical criteria rooted in evidence-based medicine are often seen as a value
      neutral 'trump card' which puts paid to any further debate about setting
      priorities for treatment. On this argument, doctors should stop providing
      treatment at the point when it becomes medically futile, and that is also the
      threshold at which the health purchaser should stop purchasing. This paper offers
      three kinds of ethical criteria as a counterweight to analysis based solely on
      medical criteria. The first set of arguments concerns futility, probability and
      utility; the second, justice and fairness; the third, consent and competence. The
      argument is illustrated by two recent case studies about futility and priority
      setting: the U.S. example of 'Baby Ryan' and the U.K. case of 'Child B'.

PMID- 15968968
TI  - Priority setting and evidence based purchasing.
AB  - The purpose of this paper is to consider the role that values play in priority
      setting through the use of EBP. It is important to be clear about the role of
      values at all levels of the decision making process. At one level, society as a
      whole has to make decisions about the kind of health provision that it wants. As
      is generally accepted, these priority setting questions cannot be answered by
      medical science alone but involve important judgements of value. However, as I
      hope to show values come into priority setting questions at another level, one
      not often explicitly recognised in much of the literature: that of the very
      definition of the effectiveness of treatments. This has important consequences
      for patient care. If we do not recognise that the effectiveness of a treatment
      involve subjective elements--a patient's own assessment of the value of the
      treatment--then this could lead to the belief that we can purchase one treatment
      that is the most effective for all patients. This might result in a detrimental
      reduction in the range of options that a patient is given with some patients not
      receiving the treatment that is most effective for them.

PMID- 15968969
TI  - Ethical issues in the economic assessment of health care technologies.
AB  - This paper challenges traditional views which oppose health economics and medical
      ethics by arguing that economic assessment is a necessary complement to medical
      ethics and can help to improve public participation and democratic processes in
      choices about resource allocation for health care technologies. In support of
      this argument, four points are emphasized: (1) Most current biomedical ethical
      debates implicitly deal with economic issues of resource allocation. (2) Clinical
      decisions, which usually respect the Hippocratic code of ethics, are nevertheless
      influenced by economic incentives and constraints. (3) Economic assessment is
      concerned with both efficiency and equity and potential trade-offs between the
      two, which means that ethical judgements are always embedded in welfare
      economics. (4) The real debate is not between economics on the one side and
      medical ethics on the other. Rather it is between different ethical conceptions
      of social justice and the contrasting approaches they entail to reconciling
      individual interests and preferences with collective goods and welfare.

PMID- 15968970
TI  - Towards cost-value analysis in health care?
AB  - By describing societal value judgements in health care in numerical terms one may
      in theory increase the precision of guidelines for priority setting and allow
      decision makers to judge more accurately the degree to which different health
      care programs provide societal value for money. However, valuing health programs
      in terms of QALYs disregards salient societal concerns for fairness in resource
      allocation. A different kind of numerical valuation of medical interventions,
      that incorporates concerns for fairness, is described. The usefulness to decision
      makers of such numerical information remains to be tested.

PMID- 15968971
TI  - Incorporating ethics in priority setting: a case study of a regional health board
      in Canada.
AB  - The authors were involved in developing an ethical framework to assist the Queens
      Region Board (Prince Edward Island, Canada) set priorities in health and health
      care. Two and one half years after the adoption of this framework, the authors
      undertook an evaluation of the framework. This paper will discuss: (a) the
      historical background of regionalization in Canada, and in particular the
      circumstances leading up to the institution of regional boards in Prince Edward
      Island; (b) the sorts of ethical issues facing the Queens Regional Board; (c)
      issues arising in connection with the use and development of ethics frameworks
      for managing ethical issues in priority setting; (d) the framework adopted by the
      Queens Board and the process that led to its development; (e) issues arising as
      concerns implementation of the framework; (f) questions and issues pertinent to
      other boards and bodies considering similar initiatives.

PMID- 15968972
TI  - Rationing decisions: from diversity to consensus.
AB  - As rationing decisions become more of an immediate reality for healthcare
      practitioners it is important to design mechanisms that facilitate carefully
      deliberated outcomes. No individual can be expected to be able to cover wide
      debate on their own, so an exercise has been designed that helps generate
      consensus decisions from diverse opinions. The exercise was piloted with two
      groups, an undergraduate medical class and the members of a general practice.
      Though the aims were different for each group, the tool was useful to both for
      producing the desired outcomes. Expert and non-expert knowledge were drawn upon
      and rationing prioritisation lists regarding funding of infertility treatment
      were generated. A description of the exercise and the results produced by the two
      groups are provided, as well as the theoretical placement for the significance of
      forming consensus from diversity.

PMID- 15968973
TI  - [Improving the nutritional value of plant foods through transgenic approaches].
AB  - The most nutrients required in the human diet come from plants. The nutritional
      quality of plant products affects the human healthy. The advance of molecular
      cloning and transgenic technology has provided a new way to enhance the
      nutritional value of plant material. Transgenic modification of plant nutritional
      value has progressed greatly in the following aspects: improving the quality,
      composition and levels of protein, starch and fatty acid in different crops;
      increasing the levels of antioxidants (e.g. carotenoids and flavonoids); breeding
      the new type of plants with medical value for human. To date, many transgenic
      plants with nutritional enhancement have been developed. These transgenic plant
      products could be directly used as human diet or as valued materials in
      developing the "functional food" with especial nutritional quality and healthy
      effects after they are approved by a series of evaluations on their safety and
      nutritional efficiency for human being. We designed new zinc finger transcription
      factors (ZFP-TFs) that can specifically down-regulate the expression of the
      endogenous soybean FAD2-1 gene which catalyzes oleic acid to linoleic acid. Seed
      specific expression of these ZFP-TFs in transgenic soybean somatic embryos
      repressed FAD2-1 transcription and increased significantly the levels of oleic
      acid, indicating that the engineered ZFP-TFs are capable of regulating fatty acid
      metabolism and modulating the expression of endogenous genes in plants.

PMID- 15968974
TI  - [The gene wxcA of Xanthomonas campestris pv. campestris 8004 strain involved in
      EPS yield].
AB  - Xanthomonas campestris pv. campestris (Xcc), the pathogenic agent of black rot
      disease in cruciferous plants, produces large amount of extracellular
      polysaccharide (EPS), which has found wide applications in industry. For the
      great commercial value of the xanthan gum, many of the genes involved in EPS
      biosynthesis have been cloned and the mechanism of EPS biosynthesis also has been
      studied. In order to clone genes involved in EPS biosynthesis, Xcc wild-type
      strain 8004 was mutagenized with transposon Tn5 gusA5, and a number of EPS
      defective mutants were isolated in our previous work. The Tn5 gusA5 inserted
      sites of these mutants were located by using thermal asymmetric interlaced PCR,
      and results showed that two EPS-defective mutants were insertion mutants of the
      gene wxcA which involved in lipopolysaccharide (LPS) biosynthesis. The gene wxcA
      involved in lipopolysaccharide biosynthesis but dose not extracellular
      polysaccharide in others' report. wxcA::Tn5 gusA5 mutant 021C12, the polar
      mutant, was complemented with recombinant plasmid pLATC8570 harboring an intact
      wxcA gene in this work, but the yield of EPS of the wxcA::Tn5 gusA5 mutant was
      not restored. In order to identify the function of wxcA gene of Xcc 8004 strain,
      the gene wxcA was deleted by gene replacement strategy, and the no-polar mutant
      of wxcA was obtained. DeltawxcA mutant strain, named Xcc 8570, was confirmed by
      using both PCR and southern analysis. Beside the LPS biosynthesis of deltawxcA
      mutant was affected, The EPS yield of deltawxcA mutant strain reduced by 50% as
      compared with the wild-type strain 8004. DeltawxcA mutant could be complemented
      in trans with the intact wxcA gene, and the EPS yield of the mutant was restored.
      The combined data showed that wxcA gene not only involved in LPS biosynthesis but
      also EPS yield in Xcc 8004 strain.

PMID- 15968975
TI  - [RNase III-prepared short interfering RNAs induce degradation of SARS-coronavirus
      mRNAs in human cells].
AB  - SARS-associated coronavirus has been identified for the cause of Severe Acute
      Respiratory Syndrome, for which there is no efficacious drugs or vaccines. RNA
      interference (RNAi) is a process in cell to degradation specific target mRNA by
      double-stranded RNA. In mammalian cells, RNAi can be triggered by short
      interfering RNA (siRNA). RNA interference of virus-specific genes has emerged as
      a potential antiviral mechanism. This work evaluated if RNase III-prepared short
      interfering RNAs can induce specific degradation of SARS-coronavirus mRNAs in
      human cells. Three of SARS genes, RNA dependent RNA polymerase (RdRp), spike and
      nucleocapsid, were amplified with T7 promoter-flanked primers. Long length double
      stranded RNA of these genes were transcribed in vitro and then were cleaved to
      <30bp length short interfering RNA with E. coli RNase III. These siRNAs were
      termed esiRNA-R, esiRNA-S and esiRNA-N respectively. RdRp, spike and nucleocapsid
      DNA fragments were inserted into the plasmid pGL3-Control, obtained plasmids pGL
      R, pGL-S and pGL-N can express hybrid mRNAs luciferase-RdRp, spike and 
      nucleocapsid in cells. Above plasmids and esiRNAs were co-transfected to HEK293F
      cells with reference plasmid pRL-TK. Firefly luciferase and Renilla luciferase
      activity were measured. Hybrid mRNAs' abundance was measured using reverse
      transcription real-time PCR. Firefly luciferase expression of pGL-R was reduced
      to 13% by esiRNA-R. Expression of pGLS was reduced to 11% by esiRNA-S. Expression
      of pGL-N was reduced to 40% by esiRNA-N. Control esiRNAs didn't affect luciferase
      expression; Hybrid mRNAs' abundance was dramatically reduced by corresponding
      esiRNAs. RNase III-prepared short interfering RNAs induce robust and specific
      degradation of SARS-coronavirus mRNAs in HEK293F cells. These siRNAs could be
      used to inhibit SARS-coronavirus in future research.

PMID- 15968976
TI  - [The cloning, high level expression in Escherichia coli of human beta-defensin 3
      and its antimicrobial activity analysis].
AB  - In recent years, Bacterial resistance is more and more serious for the irrational
      use of antibiotics produces resistant strains and other reasons. Human are trying
      to solve the problem from different ways, including the study of antimicrobial
      peptides. Defensin is one of the most important of antimicrobial peptides. A
      novel antimicrobial peptide, human beta-defensin 3, was isolated and demonstrated
      a salt-insensitive broad spectrum of potent antimicrobial activity against many
      potentially pathogenic microbes. The total RNA was extracted from human tonsil
      and the hbetaD-3 specific cDNA sequence was amplified with RT-PCR. After
      sequenced, the target DNA fragment was cloned into pQE-80L vector together with
      the DNA fragment encoding carrier protein DHFR. The recombinant vectors were
      transformed into E. coli M15 and the expression was induced based on the optimal
      values of the IPTG concentration incubation temperature and induction time
      determined in the previous section. The expressed proteins were analyzed by SDS
      PAGE and Western-blotting. The mass of the recombinant protein was about 40% of
      total bacteria protein. Isolate and purify the target protein. The recombinant
      hbetaD-3 fusion proteins possess the antimicrobial activity to staphylococcus
      aureus, multiresistant staphylococcus aureus (only vancomycin-sensitive) and
      Candida albicans in the assay of drug susceptibility. Advanced study can be
      continued based on our experiments.

PMID- 15968977
TI  - [Expression of GST-HAI-1 fusion protein and development of monoclonal antibody
      against human hepatocyte growth factor activator inhibitor 1].
AB  - The aim of this study is to develop monoclonal antibody against human hepatocyte
      growth factor activator inhibitor 1 (HAI-1) for future study of HAI-1. The cDNA
      fragments of human hepatocyte growth factor activator inhibitor 1 (HAI-1) were
      subcloned to construct GST-HAI-1 fusion protein expression vectors. The vectors
      were transformed into E. coli and fusion protein expression was induced by IPTG.
      The GST-HAI-1 fusion proteins were separated on preparative SDS-PAGE and
      recovered by electroelution, and used to immunize BALB/c mice. Hybridomas
      producing monoclonal antibodies against human HAI-1 were prepared by cell fusion
      technique and characterized by ELISA, Western Blot and immunohistochemical
      staining. One hybridoma cell line, ZMC6, was obtained, which produces specific
      antibody against the expressed GST-HAI-1 fusion protein. The monoclonal antibody
      recognizes both the membrane-type and secretory-type HAI-1 proteins of colorectal
      tissue. The successful development of anti-HAI-1 antibody provides a powerful
      tool for further investigation on HAI-1's function.

PMID- 15968978
TI  - [Growth inhibitory effects of recombinant granzyme B containing different N
      terminal translocating peptides].
AB  - Translocating protein and translocating peptides have therapeutic potential
      against tumors by exposing the cytotoxic domains of toxic proteins to the cell
      cytosol. The aim of this study is to investigate the effect of N-terminally fused
      PE translocating peptides on granzyme B (GrBa) activity. PE II-GrBa fusion
      protein genes were constructed by replacing N-terminal signal and acidic
      dipeptide sequence of human granzyme B gene with two truncated translocating
      sequences of Pseudomonas exotoxin A (PE II aa 280-364/358) by recombinant PCR,
      and then cloned into pIND inducible expression vector. The resulting pIND-PE II
      GrBa expression vectors were co-transfected with assistant plasmid pVgRXR into
      HeLa cells through lipofectamine, followed by selection on G418 and zeocin. The
      resistant cells were collected and induced with ponasterone A. Western blot
      analysis demonstrated that ponasterone A induction caused the expression of PE II
      GrBa fusion proteins, and indirect immunofluorescence detected giant sized
      multinucleated cells, suggesting cytoskeletal and mitotic abnormalities as
      reported in our previous studies. Western blot, enzymatic activity assay and cell
      counting analysis indicated that two types of PE II-GrBa fusion proteins were
      capable of cleaving both endogenous and exogenous substrates of granzyme B, and
      inhibiting the growth of cells. The PE II (aa 280-358)-GrBa was shown to have
      higher serine protease activity and stronger growth inhibitory effect. Such
      inhibition was presumably associated with G2 arrest as determined by cell cycle
      analysis. These data prove that PE II-GrBa fusion proteins have cell inhibitory
      effect similar to GrBa, and that the shorter PE-derived peptide exerts less
      influence on GrBa activity. This study helps to optimize the construction of
      recombinant protein comprising translocating peptides and cytotoxic molecules for
      tumor cell killing.

PMID- 15968979
TI  - Identification of a lens-specific cis-acting element within the basal promoter of
      the human lens intrinsic membrane protein MP19 gene (LIM2).
AB  - Using overlapping and mutant oligonucleotides as probes, gel mobility assays and
      competition experiments identified a sequence from -47 to -32 bp upstream of the
      LIM2 CAP site, which a lens protein complex bound with high affinity which
      appeared to bind only to the "sense" strand of the double-stranded DNA molecule.
      This sequence consisted of a string of four guanine residues followed by seven
      other nucleotides (AACCTAA) and followed by another four guanines, i.e.
      GGGGAACCTAAGGGG, called the Hsu element. Promoter-CAT constructs containing this
      sequence or mutations of the sequence indicated that the Hsu element is located
      within the basal promoter, and is essential for expression of the LIM2 gene. The
      trans factors binding to the Hsu element are present throughout development, and
      appear to be lens-specific. Since the LIM2 gene promoter does not contain a
      classic TATA box, the Hsu element may serve as the site for binding the RNA
      polymerase complex.

PMID- 15968981
TI  - [Sequencing and bioinformatic analysis of NRDRiso cDNA].
AB  - This study describes the cDNA sequencing and the bioinformatic analysis of a
      novel NADP(H)-dependent retinol dehydrogenase/reductases isoform (NRDRiso). Based
      upon the concensus sequences of human and mouse NRDR coding region, we have
      identified a short 377 bp RT-PCR product from human liver tissue. The cDNA
      sequence of a NRDR isoform was then isolated using RACE approach and its sequence
      was analysed. The full-length cDNA is 1,003bp in length and was submitted to
      GenBank as NADP-dependent retinol dehydrogenase/reductase short isoform
      (NRDRiso). The open reading frames of NRDRiso cDNA is 525 bp.

PMID- 15968980
TI  - [Induction of protective immunity in rhesus monkey by inoculation with
      recombinant fusion protein of cholera toxin B subunit-multivalent epitopes of
      Plasmodium falciparum].
AB  - Rhesus monkeys (5 in each group) were inoculated with recombinant fusion protein
      of cholera toxin B subunit and multi-valent epitopes of Plasmodium falciparum
      intranasal or intramuscular (i.m.). Immune-responses and protective effect were
      evaluated. The antibody titer (Geometry mean) against CTB reached 1:512
      (intranasal) and 1:10000 (i.m.) 14 day after 3rd immunization, and antibodies
      against P. falciparum were also elucidated, the titers in i.m. group were also
      significantly higher than that in intranasal group. The monkeys were challenged
      with 1.25 x 10(8) sporozoites of P. cynomolgi, Patent infection was observed in
      all 5 monkeys in control group inoculated with PBS in 10 - 14 days after
      challenge. Patent infection was also observed in 5 animals inoculated via
      intranasal and 2 animals in intramuscular group 19th days after challenge, But
      the infection last only 4 days in 3 animals in intranasal group and 2 animals in
      intramuscular group. The results demonstrated that the vaccine candidate could
      induce protective immune-responses in rhesus monkey against the challenge of P.
      cynomolgi.

PMID- 15968982
TI  - [Expression of truncated gE gene of pseudorabies virus (PRV) and primary
      application in differential diagnosis of PRV vaccination and infection].
AB  - With the application of gE gene deleted pseudarabies virus (PRV) vaccine
      worldwide, a corresponding differential diagnosis based on gE glycoprotein is
      needed in the project of PRV eradication. In this study, PRV gE gene without
      signal and transmembrane region was amplified by PCR and cloned into pGEX-6P-1,
      generated pGEX-gE. After transformation of BL21 with pGEX-gE, an expressed fusion
      protein(about 63kD) was identified by SDS-PAGE. The recombinant proteins are
      produced as inclusion bodies. By changing the inductive conditions, the formation
      of inclusion bodies was inhibited and tended to increase the percentage of
      soluble recombinant protein. The antigenic reactivity of the recombinant protein
      was confirmed by Western blotting with polyclonal antibodies against PRV. Using
      purified recombinant tgE as antigen, an ELISA was developed to detect sera of PRV
      infected pigs and sera of pigs immunized with gE-deleted PRV vaccine. The total
      of 400 serum samples collected from field were comparatively tested with the tgE
      ELISA and a commercial competitive ELISA based on monoclonal antibody against gE,
      the results indicated that the coincidental rate between the two tests is about
      94%.

PMID- 15968983
TI  - [Construction and characterization of a pseudorabies virus TK-/gG- mutant].
AB  - To construct a TK-/gG- mutant of pseudorabies virus, the gG-detected transfer
      vector pUSKKBB and genomic DNA of pseudorabies virus TK-/gG-/LacZ+ were co
      transfected into IBRS-2 cells. Transfection progeny were plated onto PK-15 cells
      and incubated for 2 days under methylcellulose. Then the overlay was removed and
      replaced by 1% low melting point agarose in DMEM supplemented with 150 microg/mL
      X-gal. After 2 days, white plaques were screened for and purified 4 times. By PCR
      amplification of gG-deleted gene and LacZ gene, a recombinant virus with TK-/gG-
      phenotype was confirmed. Sequence of the PCR product revealed that there were
      1,176 bp detection in gG gene of the PRV TK-/gG- mutant. Amplifying the gG
      deleted gene of different generations of the TK-/gG- mutant showed that the
      mutant was stable within PK-15 cells. TCID50 assay indicated that the recombinant
      virus grows well on PK-15 cells. The mice immunized with the TK-/gG- virus showed
      no sign of abnormality. As a control, all mice inoculated with PRV strain died
      from the infection. All mice that received TK-/gG- survived after a lethal PRV
      challenge. However none of the mice injected with phosphate-buffer saline (PBS)
      survived from the challenge. The above results demonstrated that the recombinant
      virus could be a candidate marker vaccine strain for eradicating pseudorabies in
      pig herds.

PMID- 15968984
TI  - [Carboxyl terminus truncated HPV58 virus L1 protein expressed with baculovirus
      system and its bioactivity].
AB  - To prepare carboxyl terminus truncated human papillomavirus type 58L1 protein,
      and study on its in vitro bioactivity. PCR was used to amplify carboxyl terminus
      truncated HPV 58L1 gene, the product was inserted into the PUCMT cloning vector,
      preparing recombinant PFastBacHTb containing carboxyl terminus truncated HPV58L1
      gene. Further more, the recombinant plasmid PfastbacHTb was used to transform
      DH10Bac cells, constructing recombinant Baculovirus, then the recombinant virus
      was successfully used to infect Sf-9 insect cells. After incubating at 27 degrees
      C for 72 hours, the infected cells were collected and total cellular proteins
      were extracted. The target protein with MW 58KD was revealed by SDS-PAGE and
      confirmed by Western blot. The interested protein was purified by ProBond
      purification system. The purified interested protein was identified to self
      assemble into VLPs by Transmission electron microscope, and induce murine
      erythrocyte hemagglutination, indicating that the given proteins had the
      conformation of VLPs, collecting, HPV58L1 proteins with carboxyl terminus
      truncation could be efficiently expressed in baculovirus Sf-9 cells expression
      system, it has identical in vitro bioactivity to the wild type HPV58L1, The
      present study is fundmental for preparing HPV58L1 prophylactic vaccine.

PMID- 15968985
TI  - [Research on TALF expression in Escherichia coli].
AB  - The expression of cDNA encoding Tachyleus auti-lipoposaccharide (LPS) factor,
      which is of interest for use as a potential inhibitor of the common core subunit
      of Gram-negative bacterial endotoxin. First, the TALF gene was inserted into
      expression vectors pGEX-4T-2, pET22b and pET28a to construct recombinant
      expression plasmids. The recombinant plasmids were transformed to E. coli BL21
      (DE3) and the expression of TALF was examined. Results show that TALF in pET22b
      and pET28a vectors can't be expressed. Only the fusion protein GST-TALF was
      expressed in E. coli BL21 existing as inclusion bodies. From 1 liter of culture,
      about 4mg of fusion protein GST-TALF with 91% purity was finally obtained. No
      apparent bactericidal activity and LPS neutralizing activity of the fusion
      protein GST-TALF were found. After digested with thrombin, the fusion protein GST
      TALF exhibited strong bactericidal activity and LPS neutralizing activity.

PMID- 15968986
TI  - [Modification and high level expression of protective antigen fragment of
      botulinum neurotoxin serotype A].
AB  - Designed a pair of primers through modifying N-terminal bases (5bps) of gene
      after ATG but not changing amino acid, and amplified a smaller mutated gene
      sequnce (468bp) containing two protective antigenic determinants from pBlue
      BoNTaHc, N-terminal codon of mutated gene fragment is changed from low to high
      frenqence in E. coli. Mutated gene was ligated into pGEM-T vector and sequenced,
      then, cloned into a expression plasmid pBV220. As a result, cloned gene was
      expressed in insoluble form by temperature inducing (from 30 degrees C to 42
      degrees C) in E. coli. Expression product is 40% of total proteins and is of
      specific binding activity to antibody in ELISA. The successful modification and
      high level expression of protective fragment of botulinum neurotoxin serotype
      A(BoNTaHc468) gene is conducive to further study on antitoxin and vaccine.

PMID- 15968987
TI  - [Cloning and analysis of cDNA encoding key enzyme gene (dxr) of the non-MVA
      pathway in Taxus chinensis cells].
AB  - Two distinct routes (classical mevalonate pathway and a novel mevalonate
      independent pathway) are utilized by plants for the biosynthesis of isopentenyl
      diphosphate, the universal precursor of isoprenoids (Fig. 1). Present researches
      indicated that taxol was synthesized mainly via non-mevalonate pathway, but not
      genetic evidence was showed. The second step in non-mevalonate pathway involves
      an intramolecular rearrangement and subsequent reduction of deoxyxylulose
      phosphate to yield 2-C-methyl-D-erythritol-4-phosphate, and 1-Deoxy-D-xylulose-5
      phosphate reductoisomerase (DXR) with responsibility for this reaction was
      considered as a key enzyme. As a tool for the isolation of genes in terpenoid
      biosynthesis in plants, total RNA was prepared from Taxus chinensis suspension
      cells, a cell type highly specialized for diterpene (taxol). A reverse
      transcription-PCR strategy based on the design of degenerated oligonucleotides
      was developed for isolating the gene encoding a gymnosperm homolog of this enzyme
      from Taxus chinensis. Through sequence analysis by Blast P online, the resulting
      cDNA showed highly homologous to 1-deoxy-D-xylulose 5-phosphate
      reductoisomerases, with 95% identification compared with Arabidopsis thaliana
      (Q9XFS9), 94% with Mentha x piperita (Q9XESO), 80% with Synechococcus elongatus
      (Q8DK30), 78% with Synechocystis sp. PCC 6803 (Q55663) and Nostoc sp. PCC 7120
      (Q8YP49), and 73% with Synechococcus leopoliensis (Q9RKT1). Deduced amino acid
      sequences were also analyzed by PROSITE, ClustalX (1.81) and Phylio (3.6 alpha),
      and data present evidence for the existence of this deoxyxyluose phosphate
      reductoisomerase in Taxus chinensis. This is the first report of the dxr gene
      cloned from gymnosperm.

PMID- 15968988
TI  - [Expression and purification of thermostable alpha-glucuronidase from Thermotoga
      maritima].
AB  - The xylanolytic enzymes found in Thermotoga maritima showed extremely high
      thermostability and considerable potential in industrial application. Yet
      expression level of the genes encoding these enzymes was very low. The alpha
      glucuronidase gene aguA from T. maritima ATCC 43589 was cloned and expressed in
      several E. coli strains with different vector. The alpha-glucuronidase was
      overexpressed in E. coli BL21-CodonPlus(DE3)-RIL with plasmid pET-28a(+), and
      made up about 20% of the total proteins present in the intracellular soluble
      fraction. The results proved the assumption that rare codons for arginine
      (AGA/AGG) and isoleucine (AUA) affect the expression of aguA gene from
      hyperthermophilic bacterium T. maritima in E. coli. Purification procedure
      included two steps, heat treatment and immobilized metal affinity chromatography,
      and over 13.5mg of pure enzyme was obrained from 1L of induced culture. The
      purified enzyme showed a single band on SDS polyacrylamide gel electrophoresis
      with a purification of 5.1 fold, and a yield of 55.1%. The optimum activity of
      recombinant alpha-glucuronidase was found at pH 6.0 and 85 degrees C, the enzyme
      retained 70% of its activity after 1 h of incubation at 85 degrees C. The
      induction conditions for expression of recombinant strain BL21-CodonPlus(DE3)
      RIL/pET-28a-aguA were studied on induction time and duration by IPTG. The results
      showed that the activity of thermostable alpha-glucuronidase reach the maximum in
      5-hour after inducted at the exponential phase (OD600 of 0.7 - 0.8).

PMID- 15968989
TI  - [Experimental study of porous TCP to generate tissue-engineered long bone].
AB  - To study bone-forming of a new kind of porous beta-TCP as the scaffold for tissue
      engineering, defects at the mid-portion of the left and right ulna were created
      in dog, the defects were repaired with beta-TCP cylinder coated with BMSCs, and
      beta-TCP cylinders alone as control. X-rays showed the defects were better
      bridged by the replant with obscure edge and new bone formed in the canal and at
      the interface in experimental group after three month of operation, whereas in
      control group, the replants were obviously deformed into dissociated granule with
      unequal density with only little new bone formed at the interface. After six
      month, the defects were bridged by new bone with osteodermatous cavum medullare
      ossium, but in control group, the defects were bridged by high density in
      radiography without osteodermatous cavum medullare ossium, the diameter of the
      ular was obviously less than experimental group. There were significant
      differences between both groups at month one and two in the development pattern
      through radionuclide observation. By gross, the diameter of ular was smaller in
      control group than in experimental at month three, and the replants in control
      group was difficult to detach from the fibroid tissue around it, but in
      experimental group, there was much more new bone formation, and the surface was
      rough for the compound of new bone and beta-TCP undegraded completely. The new
      bone in experiment had been obviously remodeled at month six, but at this moment,
      the new bone was of infirmity in volume and form. HE staining of three months
      demonstrated new bone adhered to the surface on the core of beta-TCP in
      experimental group, but in control group, at the same place, osteoid was observed
      with much megacayocytes and capillaries. At month six, beta-TCP disappeared
      completely with new bone formed in both groups, but the volume and structure of
      the bone was better in experimental group than in control group. From this study
      it is concluded that the porous beta-TCP can be combined with BMSCs, and the
      combination could generate new bone to repair long bone defect.

PMID- 15968990
TI  - [DMSO arrested hybridoma cells for enhanced antibody production].
AB  - Dimethyl sulfoxide (DMSO), a well-known differentiation inducer in several
      myeloid cells, induces G1 phase arrest in many cell lines. In this study, we
      investigated the possibility of using DMSO to arrest H18 hybridoma cells to the
      G1 phase and monitor whether the arrest improves antibody production. We showed
      that DMSO in concentration ranging between 0.3% and 0.6% efficiently arrested H18
      hybridoma cells in G1 phase. In our experiment, > 80% of cells grown for 36h in
      presence of the 0.6% DMSO were arrested in G1. Furthermore, expression levels of
      P27 were up-regulated tow fold during the G1 phase. Higher concentration of DMSO
      at 0.9% leads to cytotoxicity. Herein we show a simple way, a two-stage process
      for antibody production, which consists of a proliferation phase leading to the
      desired cell density, followed by an extended production phase during which the
      cells remain at G1 phase. Our observation that the addition of DMSO results in
      increase antibody production is of significance in further use of hybridoma cells
      in high density large scale cell culture.

PMID- 15968991
TI  - [Compared D-amino acid oxidase expression in different Pichia pastoris host
      strains].
AB  - To compare the DAAO expression level in different Pichia pastoris host strains,
      the gene encoding DAAO from Trigonopsis variabilis was cloned into plasmid
      pPIC3.5k and then transformed into P. pastoris GS115 and KM71 respectively. The
      positive transformants PDK13 (MutS) and PD27 (Mut+) were obtained by PCR
      analysis. Their optimal and different expression conditions were investigated. To
      compare with PD27, PDK13 was determined to poss a slower consumption of methanol,
      a longer induction time, a lower oxygen request and apparently higher expression
      of DAAO. The highest expression levels were reached up to 2700, 2500 IU/L in
      shaking flask and 10140, 8463.5 IU/L in fermentor respectively. The over
      expression of DAAO can meet its large demand for production of 7-ACA, alpha-keto
      acid and L-amino acid. In addition, the phenylpyruvate and L-phenylalanine were
      obtained by crude DAAO reacting with DL-phenylalanine at 37 degrees C for 3h.

PMID- 15968992
TI  - [Study on the properties of a novel glycine amino peptidase from Actinomucor
      elegans].
AB  - The glycine amino peptidase of Actinomucor elegans was studied in this work. For
      the enzyme production Actinomucor elegans was cultured with an enzyme producing
      medium. Then the cells were collected and subjected to enzyme purification. The
      glycine aminopeptidase was purified 592 times by a DEAE-Toyopearl column, a
      Toyopearl HW 65-C column and a Superdex 200 column subsequently and the purified
      enzyme had a specific activity of 14.2 u/mg. The enzyme was estimated to have
      molecular mass of 320kD by gel filtration and a subunit size of 56.5kD by SDS
      PAGE. It hydrolyzes glycine residue containing substrates such as glycine
      betanaphthylamine more efficiently than those containing other amino acid
      residue. Addition to Gly-betaNA, the enzyme could also hydrolyze Ala-betaNA, Met
      betaNA, Leu-betaNA, Arg-betaNA and Ser-betaNA but it had no activity on the
      substrates such as Trp-betaNA, Pyr-betaNA, Pro-betaNA, Asp-betaNA, Lys-betaNA,
      Val-betaNA. It was also observed when the glycine-betanaphthylamine concentration
      was higher than 2mmol/L the enzyme showed a substrate inhibition, and at the 20
      mmol/L the enzyme only showed about 55% activity as it showed at the 2mmol/L.
      Whereas no such phenomenon was observed on the other substrate such as alanine
      betanaphthylamine. The optimal temperature and pH for the reaction of this enzyme
      is 30 degrees C and pH 8.0, respectively. The Km and Kcat of the enzyme for
      glycine-betanaphthylamine is 0.24 mmol/L and 100.8 s(-1), respectively. Zn2+,
      Cu2+ and Cd2+ suppress almost all activities of the enzyme at the concentration
      of 1.0 mmol/L. Based on the study of chelating reagents, GAP belongs to the
      metalloenzyme. When a gelatin solution was hydrolyzed with 0.5% of alkaline
      proteinase together with glycine aminopeptidase at 50 degrees C for 18 hours, the
      glycine aminopeptidase could improve the hydrolysis degree of the protease. The
      total free amino acid was improved about 13% and although the enzyme mainly had
      the activity to hydrolyze the glycine residue, individual amino acids analysis
      with an amino acid analyzer showed that the contents of glycine, proline,
      alanine, arginine and glutamate were considerably increased. The results of this
      study showed that the glycine aminopeptidase would be useful in the food
      industry.

PMID- 15968993
TI  - [Purification and immobilization of chondroitinase from Aeromonas sobria YH 311].
AB  - Chondroitinase has been used as an important tool in the study of the structure,
      function and distribution of glycosaminoglycans for many years. Recently, the
      enzyme has been reported to be a potential enzyme for chemonucleolysis, an
      established treatment for intervertebral disc protrasion. In this paper, a
      chondroitinase had been purified from the culture supernatant of Aeromonas sobria
      YH311 using a simple purification procedure of ammonium sulfate precipitation,
      QAE-Sephadex A50 ion exchange chromatography and Sephadex G-150 gel filtration.
      The immobilization of purified chondroitinase using sodium alginate or cellulose
      as carriers has also been studied. The chondroitinase obtained from Aeromonas
      sobria YH311 was purified 55-fold to 95.3% pure, the specific activity of the
      purified enzyme was 31.86u/mg and the yield was 37%. The molecular weight of
      chondroitinase from Aeromonas sobria YH311 was determined by SDS-PAGE to be 80kD,
      which was almost the same as those chondroitinase AC from Arthrobacter aurescens,
      Aeromonas liquefaciens and Flavobacterium heparinum. But its isoelectric point
      was 4.3 - 4.6, which was far lower than the microbial chondroitinase AC. After
      the immobilization on sodium alginate or cellulose, the properties of
      chondroitinase changed greatly. The optimum temperature and pH of the free enzyme
      were 50 degrees C and 7.0 respectively, and about 10% activity remained after
      heat treatment at 80 degrees C for 20 minutes, and 47% activity remained after
      two weeks storage at 4 degrees C. The chondroitinase immobilized on sodium
      alginate had the optimum temperature and pH of 40 degrees C and 7.0 respectively,
      about 50% activity remained after 80 degrees C heat treatment for 120 minutes and
      50% remained after 30 days storage at 4 degrees C. The chondroitinase immobilized
      on cellulose had the optimum temperature and pH of 70 degrees C and 6.0
      respectively, and more than 70% activity remained after heat treatment at 80
      degrees C and 30 days storage at 4 degrees C. The yield of the immobilization was
      very low, with 18.56% for alginate and 18.86% for cellulose.

PMID- 15968994
TI  - [Two-dimensional electrophoresis analysis of proteins from the colleterial gland
      of silkworm (Bombyx mori L.)].
AB  - In silkworm moth the colleterial gland markedly enlarged due to the secretion and
      accumulation of glue like substances before adult emergence. However, the Ng
      mutant female moth only secreted little glue-like substance and laid loose eggs
      naturally. In the present experiment, it was extracted the proteins of secretory
      part of the variety E981 and its Ng mutant line and analyzed by two-dimensional
      electrophoresis. More than 700 protein spots were resolved both in two samples
      and most of the proteins were distributed in the area from 30 kD to 70 kD and pH
      4 - 8. Through the comparison and analysis, it was found that 4 proteins were
      only expressed in E981 and 2 proteins were only expressed in Ng mutant.
      Furthermore, there are about 29 proteins were expressed higher in 981 and about
      15 proteins expressed volume were higher in Ng mutant. These differential
      proteins may be have some relations with the Ng mutant form and directly lead to
      the Ng mutant can't secret the glue-like substance.

PMID- 15968995
TI  - [Expression and characterization of protein disulfide isomerase-related protein
      A].
AB  - Protein disulfide isomerase-related protein A (PRPA) was highly expressed (about
      34%) in Escherichia coli by inserting the whole PRPA cDNA into the vector pET23b.
      After expression, the purified protein was acquired through ammonium fractional
      precipitation and Bio-Rex 70 chromatography. PRPA shows low disulfide isomerase
      activity (only about 1/250 of that of hPDI), decreases the reactivation yield of
      denatured and reduced lysozyme either in redox and non-redox Hepes buffer or
      redox PBS buffer and facilitates the aggregation of denatured and reduced
      lysozyme. Fluorescence spectra of PRPA indicate that PRPA has more hydrophobic
      groups at surface than that of hPDI, and which can be used to explain why PRPA
      has anti-chaperone activity during the refolding of denatured and reduced
      lysozyme.

PMID- 15968996
TI  - [The primary study on the detection of sterigmatocystin by biologic enzyme
      electrode modified with the multiwall carbon nanotubes].
AB  - Sterigmatocystin (ST), the secondary metabolite of many kinds of filamentous
      fungi, is a potent carcinogen structurally related to the aflatoxins (AFT). With
      similar chemical structure, sterigmatocystion behaves much the homogeneous
      properties to aflatoxins, both of these mycotoxins exhibit similar biological
      properties due to their bisfuranoid structure. Since the common, and even heavier
      pollution, found in foods and feeds-stuff, sterigmatocystion is more harmful than
      aflatoxins. The reported detection methods of sterigmatocystion included the Thin
      layer Chromatography, the High-Performance-Liquid Chromatography, the Enzyme
      Linked Immunosorbant Assay and the PCR detection to the toxic gene, however
      studies about both easy and inexpensive electro-chemical methods have not been
      found. Our previous studies had discovered that Sterigmatocystin (ST) exist
      similar sensitivity towards aflatoxin-detoxifizyme (ADTZ), which we had isolated
      from a fungus, as aflatoxin does. In this work, the preliminary study on
      electrochemical analysis and determination of ST with triplet electrode enzyme
      biosensor system (Ag/AgCl as the reference electrode, Pt and Au as the pair and
      work electrode, respectively) was carried out. Multiwall-carbon-nanotube (MWNT)
      had been used to increase the electron transportation on electrode. In the
      research, the Au electrode was modified by MWNT-immobilized ADTZ, and then the
      voltammertric behavior of ST was studied by means of cyclic voltammogram analysis
      and different pulse analysis. Autoprobe CP Research Atomic Force Microscope and
      TECNAI 10 Transmission Electron Microscope, had been used to detect the MWNT as
      well as the surface of MWNT-modified ADTZ. The voltammertric behavior of ST was
      studied by means of cyclic voltammogram analysis and different pulse analysis.
      The results show that the red-ox peak potential of ST is at the point of -600 mV,
      the linear detection range is from 8.32 x 10(-5) to 66.56 x 10(-5) mg/mL, the
      detection limit is at 8.32 x 10(-5) mg/mL, and the response time is 10 seconds.
      This study provided a good basic work for further research.

PMID- 15968997
TI  - The labeling of 3T3-L1 preadipocyte cells with enhanced green fluorescent
      protein.
AB  - A cell model is desired for adipocyte differentiation investigation and for high
      throughput screening of anti-obesity and anti-diabetes molecules from chemical
      resources due to the world wide epidemic of obesity and diabetes. In order to
      establish such a cell model, a plasmid of pPPARgamma2-promoter-EGFP was
      constructed by inserting a 660bp sequence of mouse PPARgamma2 promoter into the
      Ase I and Kpn I sites of pEGFP-N3 and transferred into 3T3-L1 preadipocyte cells.
      The cells were induced to differentiate and the expression of PPARgamma2 was
      detected by the microscopic observation of EGFP and by RT-PCR assays. The results
      showed that the EGFP gene expression patterns were similar to that of
      pPPARgamma2's, which indicated that the EGFP gene was transferred into the mouse
      3T3-L1 preadipocyte cells, and its expression was under the control of
      pPPARgamma2 promoter. RT-PCR assays showed that the EGFP expression authentically
      represented the stable expression of PPARgamma2. In conclusion, a preadipocyte
      cell line expressing EGFP under the control of the promoter of adipocyte-specific
      expression gene PPARgamma2 was generated. The cell line provides a powerful
      approach for the research of adipocyte differentiation and for the high
      throughput screening of anti-obesity and anti-diabetes chemicals.

PMID- 15968998
TI  - [Asymmetric somatic hybridization between mixed wheat and Psathyrostachys
      juncea].
AB  - Psathyrostachys juncea is a potential source of useful genes, such as the barley
      yellow dwarf virus resistance, salt tolerance and drought tolerance, for wheat
      improvement. Conventional sexual hybridization between wheat and Psathyrostachys
      juncea is very difficult to occur as the two are sexual incompatible. Somatic
      hybridization is a promising technique for creating hybrids across the sexual
      border. Here we report a fusion system for somatic hybridization of wheat using
      PEG method. Mixed protoplasts of two wheat (Triticum aestivum L. cv. Jinan 177)
      culture cells (cha9 and 176) were used as the recipients to fuse with the donors,
      the protoplasts of Psathyrostachys juncea (Fisch.) Nevski irradiated with
      ultraviolet light (UV) at an intensity of 380 microW/cm2 for 1 min or 2 min.
      Sixteen clones were generated in the combination I, (wheat 176 + wheat cha9 + P.
      juncea 1 min UV treatment) and five of the hybrid clones could differentiate to
      green plants. All the regenerated clones were confirmed as somatic hybrids by
      cytological, isozyme, chromosome and random amplified polymorphic DNA (RAPD)
      analysis. Chloroplast genome of the hybrids was analyzed using 7 pairs of wheat
      specific chloroplast microsatellite (SSR) primers. Three clones were obtained
      from the combination II (wheat 176 + wheat cha9 + P. juncea 2 min UV treatment),
      and all browned slowly and died in 3 months. This result indicated that the mixed
      wheat cells was helpful to the formation and regeneration of hybrid callus and
      the dosage of the UV had significant effect on the development of the fusion
      products.

PMID- 15968999
TI  - [The expression of growth hormone release factor gene carried with PLGA
      microspheres in muscle tissue and its effect on mouse growth].
AB  - Injectable sustained-release pcDNA3-GRF (1-32) microspheres were prepared by
      double emulsion-in liquid evaporation process,using biodegrable poly lactic-co
      glycolic acid as carrier. The enrapment efficiency, mean particle size, drug
      content thus prepared were 69%, 2.20 microm, 8% and 70% respectively. The result
      of transfection in vivo showed that after 30 days, accumulative increased body
      weights on the group injected with pcDNA3-GRF (1-32) microspheres was
      significantly higher than those group injected with naked plasmid (12.87%),
      plasmid-empty microspheres (19.72%) and saline (58.58%) respectively. PCR and RT
      PCR showed that the expression level of GRF gene on the group injected with
      pcDNA3-GRF (1-32) microspheres was the highest. GRF gene released by microspheres
      was still detected after 30 days. In conclusion, pcDNA3-GRF (1-32) microspheres
      have a controlled release effect and GRF gene could be successfully transfected
      into muscle cells of mouse by microspheres with higher efficacy and stronger
      biological function.

PMID- 15969000
TI  - [Cloning, expression and purification of the C-terminal section of murine heat
      shock protein gp96].
AB  - Heat shock protein gp96 is a glycoprotein which was found several years ago.
      Besides its function as a molecular chaperone, it is also reported to play
      important roles both in innate immunity and adaptive immunity. Gp96 can stimulate
      the maturation of antigen presenting cells (especially dendritic cells) and the
      secretion of cytokines. Gp96 and its associated peptides could stimulate peptide
      specific cytotoxic T lymphocyte reaction (CTL), which was very promising in the
      designing of anti-virus and anti-tumor vaccines. However the expression level of
      whole length gp96 was relatively low in E. coli and the purity of gp96 are not
      very suitable for further study. We successfully cloned the carboxy terminal
      fragment (560aa-751aa) of murine gp96 into the pGEX-6p-1 vector and expressed in
      BL21 strain. This fragment contains the peptide binding domain and the
      dimerization domain. After purification, the recombinant fusion protein was
      cleaved with the PreScission Protease and analyzed by Gelfiltration. The results
      show that this fragment may be related to the dimerization of gp96 and make an
      foundation for further investigations of the protein.

PMID- 15969001
TI  - [A motif-based scanning approach for prediction of protein phosphorylation].
AB  - Scansite is a short linear motif-based scanning approach established in the
      latest two years. It's accessible over the World Wide Web and can be used to
      identify sequence motifs likely to be phosphorylated by specific protein kinases
      or likely to bind to specific protein domains such as 14-3-3, SH2 and SH3
      domains. The usage and function of the potent approach were reviewed and compared
      with previously established tools for phosphorylation prediction. The facing
      problems and application outlook of Scansite in prediction of cell signaling
      networks within proteomes were also presented.

PMID- 15969002
TI  - [Cytokine aptamers as therapeutic and diagnostic agents].
AB  - Aptamers are oligonucleotides derived from an in vitro evolution process called
      SELEX (Systematic Evolution of Ligands by Exponential Enrichment). Aptamers
      specially binding to targets could recognize and inhibit the function of targets.
      Using this method, many powerful antagonists of cytokines have been found. In
      order for these antagonists to work in animal models of disease and in humans, it
      is necessary to modify the aptamers. First of all, 2'-F, 2'-NH2 and 2'-CH3O
      modifications of nucleoside triphosphates could prolong half-lives in blood.
      Aptamers can be kept in the circulation from hours to days by conjugating them to
      higher molecular weight vehicles. After modified, conjugated aptamers are
      injected into animals, they inhibit physiological functions known to be
      associated with their target cytokines. Exhibiting binding characteristics
      comparable to or even better than monoclonal antibodies, these ligands can be
      used as detection probes, highly efficient inhibitors of protein function or
      specific competitors in high-throughput screening (HTS) assays. Recently several
      aptamers of cytokines have been characterized. Some of them have been used as
      diagnostic agent for the detection of target cytokines. The first aptamer that
      has proceeded to phase II clinical studies is NX-1838, an injectable angiogenesis
      inhibitor that can be potentially used to treat macular degeneration-induced
      blindness. Aptamers will be versatile tools that can greatly enhance the
      efficiency of modern diagnose and therapy development.

PMID- 15969003
TI  - [Advances in the research of human defensins].
AB  - Human defensin is a family of cationic antimicrobial peptides in human being.
      During the last two decades a series of endogenous alpha-and beta-human defensins
      have been discovered. They are important components of the first barrier in
      human's body against the invasion of various microorganisms, and they are thought
      to play an important role in linking the innate and adaptive defense system of
      human being. The recent advances in the research of human defensins were
      reviewed, including their discovery, molecular and genetic properties, expression
      regulation, and mechanisms of antimicrobial activity. The possibility to produce
      human defensins via genetic engineering was also discussed. And the application
      outlook of human defensins in medicine and curing patients infected with
      antibiotics-resistant microbials was presented.

PMID- 15969004
TI  - [Preliminary study of ALK3 downstream genes related to ventricular septum
      defect].
AB  - To investigate the function of ALK3 gene, the gene regulation and the signaling
      pathway related to ventricular septum defect during heart development. The model
      mice with ALK3 gene knock-out via alpha-MHC-Cre/lox P system were bred. The mRNA
      expression level of control group was compared with that of experiment group and
      ALK3 downstream genes were screened using PCR-select cDNA subtraction microarray.
      The mRNA of control group was extracted from E11.5 normal mouse hearts, and that
      of experiment group, from E11.5 hearts of mice with alpha-MHC Cre(+/-) ALK3(F/+)
      genotype. It was found that the mice with ALK3 gene knock-out produced heart
      defects involving the interventricular septum. The platelet-activating factors
      acetylhydrolase and the transcription factor Pax-8 and so on, were down
      regulated. However, the Protein Tyrosine Kinase (PTK) of Focal Adhesion Kinase
      (FAK) subfamily and beta subtype protein 14-3-3 were up-regulated in the alpha
      MHC Cre(+/-) ALK3(F/-) mice. These data provide support that ALK3 gene played an
      important role during heart development. The platelet-activating factors
      acetylhydrolase and Pax-8 genes could be important ALK3 downstream genes in the
      BMP signaling pathway during interventricular septum development. PTK and beta
      subtype protein 14-3-3 might be regulatory factors in this pathway.

PMID- 15969005
TI  - [One amino acid mutation in an anti-CD20 antibody fragment that affects the yield
      bacterial secretion and the affinity].
AB  - Monoclonal antibodies (mAb) directed against CD20, either unmodified or in
      radiolabeled forms, have been successfully exploited in clinic as effective
      therapeutic agents in the management of non-Hodgkin's B-cell lymphoma. The
      antibody fragment is a potential agent in image and therapy of tumor. To further
      improve the soluble expression of anti-CD20 antibody Fab' fragment, PCR was used
      to mutate the anti-CD20 VL and VH genes and its biological activity was
      identified. The expression vector of chimeric antibody Fab' was constructed and
      expressed in E. coli. The data of mutant clone DNA sequence showed that the amino
      acid of light chain gene of the parent anti-CD20 antibody (H47) was successful
      mutated as Ser (GAG)-Asn (CAG). The soluble expression of mutated anti-CD20 Fab'
      (CD20-7) was 3.8 mg/g dry cell weight, while the parent (CD20-2) was 1.3 mg/g dry
      cell weight. The affinity constant Ka of CD20-7 was 2.2 x 10(9) L/mol. The
      primary results of competitive assays by FACS showed that CD20-7 could partially
      block the sites through which parent antibody (HI47) bind to Raji cells. There
      was difference in the Raji cells (CD20+)-binding activity between the mutant CD20
      7 and parent CD20-2. The site mutation of anti-CD20 Fab' gene make it possible
      that the anti-CD20 antibody fragment was succeeded to obtain higher expression.
      In this thesis, we succeeded in completing mutation and expression of anti-CD20
      Fab' genes, distinguishing its biological activity, and obtaining its highly
      expression. These period results will lay a foundation for development of other
      kind of anti-CD20 engineering antibody (for instance: Fab' Diabody and
      miniantibody), and make it possible for anti-CD20 antibody to be applied to tumor
      therapy in civil in the future.

PMID- 15969006
TI  - [Construction of MAGE-3 prokaryotic expression plasmid and its expression in
      Escherichia coli].
AB  - To express the GST-MAGE-3 protein in E. coli, and investigate the antitumor
      immune responses induced by Dendritic cells (DCs) pulsed with GST-MAGE-3 protein,
      the recombinant expression plasmid pGEX-MAGE-3 was constructed by ligating MAGE-3
      gene, which was amplified by RT-PCR and confirmed by sequencing, and the pGEX-4T
      2 vector. The recombinant plasmid was transformed into BL-21 E. coli. The
      expression of GST-MAGE-3 was induced with IPTG. The GST-MAGE-3 protein expressed
      as high as 32% of the total cellular protein. After purification with Glutathione
      Sepharose 4B, the purity of the protein was more than 90%, and 3mg GST-MAGE-3 was
      obtained from 100 mL BL-21 lysate. Dendritic cells from gastric carcinoma
      patients were pulsed with GST-MAGE-3 protein, and these DCs were used to
      stimulate the autologous T. lymphocytes. After 7 days, the T. lymphocytes
      cocultured with DCs pulsed with GST-MAGE-3 antigen exhibited specific
      cytotoxicity against MAGE-3 positive SGC-7901 cells. It is concluded that the GST
      MAGE-3 protein are able to present antigen to T. lymphocytes, activate antigen
      specific CTLs and induce special antitumor immune responses in vitro. Our results
      lay the groundwork for further research of the MAGE-3 vaccine.

PMID- 15969007
TI  - [Construction of gene library of Arthrobacter BT801 and isolation & expression of
      hydantoinase gene].
AB  - Hydantoinase can be widely used in enzymic production of various amino acids. In
      order to obtain the hydantoinase genes in Arthrobacter BT801, its chromatosomal
      DNA is isolated and partialy digested with Sau3A I to collect fragments of about
      30kb. Then, this fragment is inserted into the Hpa I and Pst I site of cosmid
      pKC505. The genomic library was thus constructed by packing in vitro with lambda
      phage package protein and transfecting E. coli DH5alpha. A positive transformant
      was selected from the library using thin layer chromatography and other methods.
      A DNA fragment containing complete hydantoinase genes was sequenced by sub
      cloning into pUC18. The gene can express active protein under control of its own
      promoter and T5 promoter in E. coli. The isolation of the gene established
      foundition for research and application of the hydantoinase.

PMID- 15969008
TI  - [Secretion expression of Mt. heat shock protein 70 in Pichia pastoris and
      identification of the protein].
AB  - To obtain the expression of Mycobacterium tuberculosis heat shock protein 70 in
      methylotropic yeast. The expression vector pPIC9K-hsp70 was constructed,
      linearized and introduced into Pichia pastoris GS115 by electroporation. The
      result protein was secreted into the supernatant induced by 0.5% methanol at 30
      degrees C and purified by centrifugation, ultrafiltration and ATP-agarose. The
      recombinant Hsp70 was identified by SDS-PAGE, Western blot, mice experiment and
      effect on the immature DC. The SDS-PAGE and Western blot analysis showed that the
      apparent molecular weight of expressed Hsp70 was about 70 kD and the expressed
      protein could specifically react with anti-Mt. Hsp70 IgG. And mice immunization
      indicated the expressed hsp70 had immunogenicity. Hsp70 could induce DC
      maturation and release Th1 cytokine. The secreted 70 kD protein was about 120
      mg/L which accounted for more than 30% of the total supernatant protein and was
      purified to electrophoretic purity. The Hsp70, which had the biological activity,
      is successfully secretorily expressed in the Pichia pastoris GS115.

PMID- 15969009
TI  - [Preparation of antibodies against a novel leucine-zipper protein, Ecp].
AB  - The aim of this research is to prepare high quality polyclonal antibodies against
      Ecp, a recently identified leucine-zipper protein. The full length cDNA of ecp
      was amplified by PCR, cloned into pGEX-4T-1(His)6 and transformed into E. coli DH
      5alpha. After induction with IPTG, the GST-Ecp fusion protein from the lysate was
      bound to glutathione-Sepharose 4B and digested with thrombin. The released Ecp
      protein was further purified through Ni-NTA affinity chromatography to
      homogeneity. A rabbit was immunized with the purified Ecp, and the antibody
      generated against Ecp was purified by affinity chromatography. The results of the
      Western blot showed that Ecp is present in various development stages of
      Drosophila melanogaster, from larvae to adult.

PMID- 15969010
TI  - [HRCA and application in detection of genetically modified plant].
AB  - In this article primary studies of the application of hyperbranched rolling cycle
      amplification (HRCA) in exogenous genes detection of transgenic plants were done.
      Four padlock probes were designed according to the sequences of four genes/DNA
      fragments that are used widely in transgenic plants; part of the sequence of
      pKK233 was chosen as the linking part of padlock probes and a pair of HRCA
      primers was designed according to the sequence of linking part. Study of the
      specificity of ligation in HRCA with isotope labeled padlock probes indicated
      padlock probes could be ringed effectively only when corresponding target DNA
      exited in the same reaction system and could not be ringed when there was no
      corresponding target DNA exited. Ligation time is very different according to the
      characteristic of target DNA being used. 5 min to 10 min is enough if the target
      DNA is plasmid; 30 min to 60 min is needed if the target is genome DNA of plant
      because it's sequence is more complex than that of plasmid's. HRCA time was
      analyzed which indicated longer reaction time can obviously increase the amount
      of products. Quantity of enzyme in HRCA was also analyzed. Different amount of
      enzyme (from 0.5 unit to 4 units) can give similar result when other conditions
      are not changed. On the basis of the research, transgenic tobacco was detected
      with these four padlock probes and the results were just as prospective. In order
      to increase the efficiency of detection, multiplex HRCA (MHRCA)was used. In MHRCA
      more than one padlock probes are used at the same time in the same reaction
      system to detect more than one targets. Because the amplification products of
      MHRCA will be complex and it is almost impossible to analyze with
      electrophoresis, so reverse-blot is used. Detection results of transgenic tobacco
      with this method are the same with anticipation. Compare to MPCR method we
      established before MHRCA is more convenient to operate and more effective in
      detecting exogenous genes in transgenic plants.

PMID- 15969011
TI  - [Co-expressions of phosphoenolpyruvate synthetase A (ppsA) and transketolase A
      (tktA) genes of Escherichia coli].
AB  - Metabolic engineering is the analysis of metabolic pathway and designing rational
      genetic modification to optimize cellular properties by using principle of
      molecular biology. Aromatic metabolites such as tryptophan, phenylalanine, and
      tyrosine are essential amino acids for human and animals. In addition,
      phenylalanine is used in aspartame production. Escherichia coli and many other
      microoganism synthesize aromatic amino acids through the condensation reaction
      between phospho-enolpyruvate (PEP) and erythrose-4-phosphate(E4P) to form 3-deoxy
      D-arabinoheptulosonate 7-phosphate(DAHP). But many enzymes compete for
      intracellular PEP, especially the phosphotransferase system which is responsible
      for glucose transport in E. coli. This system uses PEP as a phosphate donor and
      converts it to pyruvate, which is less likely to recycle back to PEP. To channel
      more carbon flux into the aromatic pathway, one has to overcome pathways
      competing for PEP. ppsA and tktA are the key genes in central metabolism of
      aromatic amino acids biosynthesis. ppsA encoding phosphoenolpyrucate synthetase A
      (PpsA) which catalyzes pyruvate into PEP; tktA encoding transketolase A which
      plays a major role in erythrose-4-phosphate (E4P) production of pentose pathway.
      We amplified ppsA and tktA from E. coli K-12 by PCR and constructed recombinant
      plasmids of them in pBV220 vector containing P(R)P(L) promoter. Because of each
      gene carrying P(L) promoter, four productions of ligation were obtained. The
      monoclonal host containing recombinant plasmids was routinely grown in Luria
      Bertani (LB) medium added Ampicillin at 37 degrees C overnight, and then
      inoculated in LB (Apr) medium by 3%-5% in flasks on a rotary shaker at 30 degres
      C, induced at 42 degrees C for 4.5 hours when OD600 = 0.4, cells were obtained by
      centrifugation at 10,000 r/min at 4 degrees C. The results of SDS-PAGE
      demonstrated that the bands at 84kD and 73kD were more intensive than the same
      ones of the controls. The specific activity of PpsA in crude extracts was
      increased by 10.8-fold, and TktA, by 3.9-fold. When both genes were co-expressed
      in E. coli, the activity of PpsA varied from 2.1-9.1 fold comparing to control,
      but the activity of TktA was relatively stable(3.9-4.5 fold). Whatever the two
      genes were expressed respectively or cooperatively, both could promote the
      production of DAHP, the first intermediate of the common aromatic pathway, but co
      expression was more effective on forming DAHP. The results demonstrate that co
      expression of ppsA and tktA can improve the production of DAHP to near
      theoretical yield. This report details a different strategy based on co
      expression of two genes in one vector in vivo to release the burden and paves the
      way for construction of genetic engineering bacteria for further research.

PMID- 15969012
TI  - [Induction of hairy roots of Pueraria phaseoloides and its culture in liquid and
      solid medium].
AB  - An efficient transformation system for genetic transformation of medicinal plant,
      Pueraria phaseoloides, which contains puerarin and daidzein with hypothermic,
      spasmolytic, hypotensive and anti-arrhythmic activities, by using agropine-type
      Agrobacterium rhizogenes ATCC 15834 was developed. Hairy roots could be obtained
      directly from the cut edges of petioles of leaf explants of P. phaseoloides or
      via callus 20 days after inoculation with agrobacterium. The percentage of rooted
      leaf explants 35 days after infection was about 85%. Hairy roots could have a
      rapid growth on solid or liquid growth regulator-free MS medium. The
      transformation of hairy roots was confirmed by PCR amplification of rol B and rol
      C genes of Ri plasmid from A. rhizogenes. To investigate the physiological
      difference between solid and liquid culture, the biomass (fresh weight and dry
      weight), the reactive oxygen species (ROS) and the total content of soluble sugar
      in hairy roots cultured for 15 days in solid and liquid medium were detected,
      respectively, by the method of fluorescence labeling of 2',7'-dichlorofluorescein
      diacetate (2',7'-DCFH-DA) and by the anthrone colourimetry. Compared to hairy
      roots in solid medium, hairy roots grew more rapidly in liquid medium but formed
      no callus and appeared to become brown earlier during culture. The fresh weight,
      the dry weight, the total content of soluble sugar and the levels of reactive
      oxygen species of hairy roots cultured into liquid medium MS without plant growth
      regulators for 15 days were 1.59 times, 1.18 times, 5.25 times and 1.16 times,
      respectively as much as that of hairy roots cultured onto solid medium. Our
      results firstly indicate that P. phaseoloides hairy roots in solid medium can
      utilize or metabolize more soluble sugar but produce less reactive oxygen species
      than that in liquid medium. This may be related to the fact that hairy roots are
      easier to turn brown in liquid medium than that onto solid medium. Our results
      have laid a foundation for defining optimum culture manner for large-scale
      cultivation and large-scale production of secondary metabolites of P.
      phaseoloides hairy roots.

PMID- 15969013
TI  - [The investigation of hematopoietic capacity of HPP-CFC derived from murine
      embryonic stem cells in vitro and in vivo].
AB  - The hematopoietic system of the mouse arises from extraembryonic mesoderm that
      migrate through primitive streak to the presumptive yolk sac at day 7.0 of
      gestation. However, the mechanisms regulating mesoderm commitment to
      hematopoietic lineages remain poorly understood. Previous studies demonstrated
      that the development kinetics and growth factor responsiveness of hematopoietic
      precursors derived from embryonic stem cells (ES cells) is similar to that found
      in the yolk sac, indicating that the onset of hematopoiesis within the embryoid
      bodies (EBs) parallels that found in the embryo. Furthermore, in vitro
      differentiation of ES cells to hematopoietic cells is valuable for establishment
      of therapeutic clone against a variety of hematological disorders. Despite the
      identification of multipotential hematopoietic progenitors in EBs, a subset of
      more primitive progenitors, identical to the high proliferative potential colony
      forming cells (HPP-CFC) derived from human and murine hematopoietic tissues, have
      not been clearly identified regarding particular their replating potential in
      vitro. HPP-CFC is among the most primitive hematopoietic multipotent precursors
      cultured in vitro. In this study, our aim was to investigate the in vitro and in
      vivo hematopoietic capacity of HPP-CFC within the day 12 EBs, rather than the
      expansion of more committed progenitors. In this study the HPP-CFC could be
      detected within EBs differentiated for 5 to 14 days of murine ES cells, but the
      development dynamics of the HPP-CFC differed greatly among distinct serum lots.
      Qualitatively HPP-CFC is capable of forming secondary colonies. As to our
      expectation the ES cells-derived HPP-CFC demonstrated similar regeneration
      capacity to those from yolk sac, giving rise to secondary granulocyte,
      erythrocyte, macrophage and mast cells, however largely differed from the
      counterparts of adult bone marrow. In addition, by RT-PCR ES cells-derived HPP
      CFC were found to express transcription factors associated closely with stem cell
      proliferation including SCL, GATA-2 and AML1 as well as various receptors of
      hematopoietic growth factors such as c-kit, GM-CSF receptor and interleukin 3
      receptor et al. Finally, in order to understand the in vivo hematopoietic
      capacity of the ES cells-derived HPP-CFC, spleen colony-forming unit (CFU-S)
      assay was performed. Nevertheless, typical CFU-S was not observed after
      transplantation of the day 12 EB cells or HPP-CFC colonies into lethally
      irradiated adult murine. In conclusion the HPP-CFC differentiated from murine ES
      cells displayed robust hematopoietic activity in vitro, however their in vivo
      reconstitution ability was not detected. The difference between in vitro and in
      vivo hematopoietic activities of ES cells-derived primitive hematopoietic
      precursors deserves further investigation.

PMID- 15969014
TI  - [The role of cortical microtubules in moss protonemal cells during
      dehydration/rehydration cycle].
AB  - Plant cells response to water deficit through a variety of physiological
      processes. In this work, we studied the function of microtubule cytoskeleton
      during dehydration/rehydration cycle in moss (Atrichum undulatum) protonemal
      cells as a model system. The morphological and cytological change of protonemal
      cells during dehydration and rehydration cycle were first investigated. Under
      normal conditions, protonemal cells showed bright green colour and appeared wet
      and fresh. Numerous chloroplasts distributed regularly throughout the cytoplasm
      in each cell. After dehydration treatment, protonemal cells lost most of their
      chlorophylls and turned to look yellow and dry. In addition, dehydration caused
      plasmolysis in these cells. Upon rehydration, the cells could recover completely
      from the dehydrated state. These results indicated that moss had a remarkable
      intrinsic ability to survive from the extreme drought stress. Microtubule, an
      important component of cytoskeleton, is considered to play crucial roles in the
      responses to some environmental stresses such as cold and light. To see if it is
      also involved in the drought tolerance, dynamic organization of microtubules in
      protonemal cells of Atrichum undulatum subjected to drought and rehydration were
      examined by indirect immunofluorescence combined with confocal lasersharp
      scanning microscopy. The cortical microtubules were arranged into a fine
      structure with a predominant orientation parallel to the long axis of the cells
      in the control cells. After dehydration, the microtubule organization was
      remarkablly altered and the fine microtubule structure disappeared whereas some
      thicker cables formed. When the cells were grown under rehydration conditions,
      the fine microtubule arrays reappeared. These results provided a piece of
      evidence that microtubules play a role in the cellular responses to drought
      stress in moss. Furthermore, we analyzed the effects of the microtubule
      disrupting agent colchicine on the morphology recovery of the protonemal cells
      during rehydration process. The cells were incubated with colchicine, followed by
      drought stress treatment and rehydration in the presence of colchicine to prevent
      recovery of microtubule organization. Results from immunofluorescence showed that
      microtubule arrays were broken down into smaller fragments. Compared to the cells
      treated with drought stress alone, the cells treated with drought stress in the
      presence of colchicine could not recover after rehydration treatment. The
      morphology resembled those of the drought treated cells, with obvious plasmolysis
      phenomena and loss of chlorophyll content. These results support the notion that
      microtubules were involved in the deccication tolerance mechanism in Atrichum
      undulatum.

PMID- 15969015
TI  - [Construction of an anti-apoptosis CHO cell line for biopharmaceutical
      production].
AB  - Mammalian cells are prone to apoptosis when cultured in large scale for
      production of biopharmaceuticals. And this will reduce production duration and
      result in high cost of production. Apoptosis is triggered by various factors, and
      delicately regulated by a set of genes. Bcl-2, a component integrated in
      mitochondria membrane, is an important member of these genes. By maintaining the
      integrity of mitochondria membrane, Bcl-2 keeps cytochrome C from releasing into
      cytoplasm, and thus blocks the activation of caspases, and subsequent onset of
      apoptosis. Over-expression of Bcl-2 has proven to be useful in blocking apoptosis
      in various cell lines, including CHO, hybridoma, myeloma, lymphoma and insect
      cells. Ammonia, a metabolite of cultured cells, however, showed apparent pro
      apoptosis activity. In living cells, ammonia can be utilized by glutamine
      synthetase (GS) to synthesize glutamine, and thus lower the concentration of
      ammonia in medium, and its negative effects. Glutamine is essential to living
      cells. If not added into medium, glutamine can only be synthesized by GS, which
      makes GS a qualified selection marker. This marker can be used for gene
      amplification by adding into medium increased concentration of MSX, an inhibitor
      of GS. In this study, we over-expressed Bcl-2 using GS amplification in a
      recombinant CHO cell line stably expressing human interferon-beta. The modified
      cell line, with higher expression of Bcl-2 and lower production of ammonia,
      exhibited good anti-apoptosis quality and higher interferon-beta production in
      continuous culture.

PMID- 15969016
TI  - Purification and properties of Bacillus subtilis SA-22 endo-1, 4-beta-D
      mannanase.
AB  - beta-mannanase (EC 3.2.1.78) from Bacillus subtilis SA-22 was purified
      successively by ammonium sulfate precipitation, hydroxyapatite chromatography,
      Sephadex G-75 gel filtration and DEAE-52 anion-exchange chromatography. Through
      these steps, the enzyme was concentrated 30.75-fold with a recovery rate of
      23.43%, with a specific activity of 34780.56 u/mg. Molecular weight of the enzyme
      was determined to be 38 kD by SDS-PAGE and 34 kD by gel filtration. The results
      revealed that the optimal pH value for the enzyme was 6.5 and the optimal
      temperature was 70 degrees C. The enzyme is stable between pH 5 to 10. The enzyme
      remained most of its activity after a treatment of 4 h at 50 degrees C, but lost
      25% of activity at 60 degrees C for 4 h, lost 50% of activity at 70 degrees C for
      3 h. The enzyme activity was strongly inhibited by Hg2+. The Michaelis constants
      (Km) were measured as 11.30 mg/mL for locust bean gum and 4.76 mg/mL for konjac
      powder, while Vmax for these two polysaccharides were 188.68 (micromol x mL(-1) x
      min(-1)) and 114.94 (micromol x mL(-1) x min(-1)), respectively.

PMID- 15969017
TI  - [The preparation and application of cross-linked urease aggregates].
AB  - Urease was immobilized in a simple and effective way by physical aggregation
      using a precipitant-ammonium sulfate, followed by chemical cross-linking using a
      bifunctional reagent-glutaraldehyde to form insoluble Cross-linked urease
      aggregates (CLUAs). The optimum pH, optimum temperature and Km of CLUAs were 8.0,
      70 degrees C and 0.021 mol/L respectively. Compared with that of free urease, the
      thermal stability, storage stability and resistance of cross-linked urease
      aggregates to the exogenous proteolysis were enhanced. The efficacy of CLUAs for
      the treatment of rats with chronic renal failure was also studies. The rats with
      chronic renal failure caused by adenine were divided into 3 groups randomly:the
      control group (fed with 10 mL water /kg per day), Coated Aldehyde Oxystarch (CAO)
      group (fed with 20 g CAO /kg and 10 mL water /kg per day) and CLUAs + CAO group
      (fed with 20 g CAO /kg and 10 mL CLUAs /kg per day) in which CAO was used to
      absorb the ammonia produced from urea. The contents of BUN and Scr in serum
      before and after 2 weeks treatment were determined. In three groups, the level of
      Scr decreased slightly (P = 0.922, 0.972 and 0.225 > 0.05 respectively) after
      treatment. The level of BUN was not changed (P = 0.211 > 0.05) in the control
      group, but decreased greatly BUN in both CAO group and CLUAs + CAO group (P =
      0.004 < 0.05 and P < 0.001 respectively). Furthermore, the decrease of the BUN
      level after treatment in the CLUAs + CAO group was more remarkable than that in
      the CAO group (P = 0.016 < 0.05), which showed that the CLUAs + CAD system was
      more efficient than the CAO system for the removal of urea in serum.

PMID- 15969018
TI  - [Soluble expression of peptide containing MUC1/Y-specific epitope in Escherichia
      coli and preparation of the antibody].
AB  - MUC1 mucin is a high molecular weight, type I transmembrane glycoprotein. High
      and aberrant expression of MUC1 is observed in various types of tumors, which
      make it an ideal target for tumor biotherapy as well as a biomarker for tumor
      diagnosis and prognosis. MUC1/Y is an isoform of MUC1 generated by alternative
      splicing. Specific expression of MUC1/Y in breast cancer as well as its
      involvement in tumor cell signal transduction have been reported. In order to
      purify peptides containing MUC1/Y-specific epitope in E. coli and prepare MUC1/Y
      specific antibody, DNA fragment encoding the MUC1/Y-specific peptide was
      amplified by PCR using MUC1/Y full length cDNA as the template and cloned into
      fusion expression vector pGEX-2T, resulting pGEX-Y30. DNA sequencing was
      performed to confirm the correct amplification and orientation of the target
      sequence. Competent E. coli DH5alpha was transformed with pGEX-Y30 and the
      expression was induced for 4-5 hours in 0.2 mmol/L IPTG at 30 degrees C and 37
      degrees C. Expressed proteins were released from the cells by ultrasonication or
      B-PER II reagent treatments. The fusion protein GST-Y30 were purified by affinity
      and anion exchange columns and identified by SDS-PAGE and Western-blotting.
      Polyclonal antibody was prepared by immunizing rabbits with the GST-Y30 protein
      for 4 times with intervals of 3 weeks and purified by GST column. Western
      blotting, ELISA and immunohistochemistry analysis were carried out using the
      purified antibody to confirm its MUC1/Y-binding capacity and specificity. The
      expressed fusion protein GST-Y30 is about 31 kD in size and represented about 20%
      of total cellular proteins. The majority of the GST-Y30 protein existed as
      soluble form when the induction was carried out at both 30 degrees C and 37
      degrees C. After the two-step purification, the purity of GST-Y30 was about 94%.
      The titer of polyserum generated by GST-Y30 immunization was 1:320,000 by ELISA.
      The antiserum showed MUC1/Y specificity and can recognize MUC1/Y on MCF7 cell.
      The MUC1/Y-specific polyclonal antibody can be used for studying the role of
      MUC1/Y in carcinogenesis.

PMID- 15969019
TI  - [Uptake of nickel from industrial wastewater by genetically engineered
      Escherichia coli JM109].
AB  - Heavy metal wastewater poses a serious threat to the environment. In comparison
      to the existing methods of chemical precipitation, ion exchange and carbon
      adsorption, biosorption is an attractive alternative for the recovery of heavy
      metals from industrial effluents. However, nickel ion, different from other heavy
      metal ions, is a more recalcitrant pollutant and has low affinity to many metal
      tolerant microorganisms. In this study, Escherichia coli JM109 was genetically
      engineered to simultaneously express a Ni2+ transport system (the product of nixA
      gene) andoverexpress metallothionein (MT). NixA protein has a high affinity for
      Ni2+, and metallothioneins (MTs) are capable of binding a variety of heavy metals
      including Ni2+ . The Ni2+ bioaccumulation performance of the genetically
      engineered E. coli JM109 was evaluated. Time-course test showed that the
      bioaccumulation rate was rapid, and 95% of the accumulation was achieved within
      the first 10 minutes. The maximum Ni2+ bioaccumulation by genetically engineered
      E. coli cells was dramatically increased from 1.54 mg/g to 10.11mg/g, a more than
      five-fold increase than that of the original E. coli strain. The isotherm was of
      Langmuir type. Within the tested pH range (pH 4-10), the engineered cells
      displayed more resistance to pH variation, retaining up to 80% of the Ni2+
      binding capacity at pH 4, while the original E. coli host cells lost 80% of Ni2+
      binding capacity at pH 4. The presence of Na+ and Ca2+ affected Ni2+
      bioaccumulation, but the effects were not serious, as 71% and 66% of the Ni2+
      binding capacities were retained respectively at the concentrations of 1000 mg/L
      Na+ and 1000 mg/L Ca2+ . However, Mg2+ exerted a severe adverse effect on Ni2+
      bioaccumulation, 83% of Ni2+ accumulating capacity was lost when Mg2+
      concentration reached 200 mg/L. The effects of different kinds of heavy metals on
      Ni2+ accumulating were different. The genetically engineered E. coli cell lost
      less than 45% of its Ni2+ bioaccumulation activity in the presence of 50 mg/L
      lead or cadmium, 66% in the presence of 25mg/L mercury and 84% in the presence of
      40 mg/L copper. The presence of glucose did not improve Ni2+ uptake. Our study
      suggests that the genetically engineered E. coli JM109 has potential application
      for effective and efficient recovery of nickel from aqueous solutions.

PMID- 15969020
TI  - [Establishment and application of the model of islet impaired by NO free radical
      released from streptozotocin].
AB  - For diabetes mellitus, little research has been done on the tissue-based or cell
      based drug screening model, which has advantages over traditional animal diabetic
      model in high specificity, high screening volume, low cost and simple
      manipulation. Considering that the maintenance of complete islet tissue structure
      is the prerequisite for islet cells to perform their functions normally, an in
      vitro islet-based drug screening model for diabetes mellitus was established and
      evaluated. Pancreatic islets were isolated from 3 weeks old mice of either sex by
      collagenase digestion and density gradient centrifugation as prescribed by
      Ramanadham S. The volume of 0.1% (W/V) collagenase IV, 0.1% (W/V) Hyaluroridase
      and 0.1% (W/V) DNase I were 4 times, 2 times and 1 times that of the islets to be
      digested. And a 2 hours' cold digestion at 4 degrees C was followed by a 10
      minutes' warm digestion at 37 degrees C. Under the optimized digestion condition,
      the islet recovery could be increased by 10%. The isolated islets could survive 6
      weeks in vitro and show stable insulin secretion in the first 10 days after
      inoculation. The obtained islets were cultured in RPMI-1640 medium at 37 degrees
      C with 5% CO2. Then a diabetic model was established by selecting streptozotocin
      (STZ) as the evocator and nitric oxide (NO) as the responding index. After 1
      day's inoculation, islets culture was treated with STZ, whose concentration
      ranged from 0 to 5.0 mmol/L. NO was measured by a colorimetric assay at 540nm
      based on the Griess reaction for 10 min with 0.1 mL Griess reagent and 0.1 mL
      culture supernatants. Insulin secretion was assayed by RIA methods. Due to the
      islets-related inoculation variations, NO release and insulin content were both
      expressed as a percentage of the value recorded in basal experiment which was in
      the only presence of Krebs culture medium. It was testified that the amount of NO
      released from islet itself remained steady at 30-35 mmol/L regardless of the
      changes of STZ concentration from 0 to 5.0 mmol/L. However the NO content in the
      supernatants of islets culture had close relationship with STZ concentration.
      This indicated that in this STZ-induced islet diabetic model, NO mainly comes
      from STZ when it dissolves in water. On the other hand, when STZ changed from 0
      to 5.0 mmol/L, the dose-dependent relationship between NO content and insulin
      secretion showed that the increase of NO came along with the decrease of insulin
      secretion, which is an important symbol of islet function. As a kind of oxidative
      free radical, NO is capable of impair islet cells. Thus, NO is a reliable
      responding index of the model. The optimal STZ concentration in the model is
      finally determined to be 5.0 mmol/L, under which condition the NO content and
      insulin secretion is 10.81 times and 0.43 times that in the medium before STZ is
      added. So if anything is effective in lowering the NO content in the culture, it
      could protect islets cells from the oxidative attacks of NO. Finally, as an
      application of the model, the scavenging effect of KOSCr on NO was studied. In a
      series of KOSCr with different chromium content, all had shown better NO
      scavenging effects than KOS itself, which could give us an enlightenment of the
      influence of chromium ion on oligosaccharide. And 1 g/mL KOSCr with 3.519%
      chromium content can significantly inhibit the NO formation. This has lain a
      theoretic basis for the research of KOSCr bioactivity and quality control. These
      results suggested that the STZ-induced diabetic islet model which is impaired by
      NO free radical can be used effectively, fast and conveniently when screening
      potential diabetes drugs.

PMID- 15969021
TI  - Molecular cloning and sequence analysis of ussurin, a new
      metalloproteinases/disintegrin from Gloydius ussuriensis.
AB  - The metalloproteinases/disintegrins in the snake venom act as platelet
      aggregation inhibitor by an antagonism against integrin on platelet through its
      RGD sequence and may play other important role in cell-cell fusion, cell matrix
      interaction and other cellular function. Ussurin is a new
      metalloproteinase/disintegrin that was cloned from Gloydius ussuriensis. Poly
      (A+) RNA was purified from the total RNA preparation from venom gland of a single
      G. ussuriensis using the poly (A+) tract-mRNA isolation system. A cDNA library
      was constructed with the SMART PCR cDNA library construction kit. The cDNA
      library was screened and the positive clones were selected. The full-length cDNA
      of Ussurin was obtained. The cDNA encoding the Ussurin precursor has a 51bp 5'
      UTR, the open reading frame of Ussurin and a 490 bp 3'-UTR, the open reading
      frame of Ussurin cDNA nucleotide sequence is 1434 bp and codes for 478 amino
      acids with a predicted molecular mass of 53.2 kD and an isoelectric point of
      5.37. There is no potential N-glycosylation site in the deduced sequence region.
      Its deduced amino acid sequence consists of four region, a signal sequence of 18
      amino acid residues, a zymogen pro-peptide of 171 amino acid residues with a
      cysteine switch motif (PK-MCGVT) in it, a central metalloproteinase domain of 201
      amino acid residues containing a conserved zinc-chelating sequence (HEXXHXXGXXH)
      and a methionine-turn CIM involving zinc banding also, a space sequence between
      metalloproteinase domain and disintegrin domain of 15 amino acid residues with a
      conserved T392, T397, S400, which is specific residues of the P-II snake venom
      metalloproteinases, a disintegrin domain of 73 amino acid residues with a
      characteristic RGD region and six-disulfide bonds. Ussurin belongs to P-II class.
      The cDNA sequence and deduced amino acid sequence of Ussurin precursor were
      compared with homologous sequence in the GenBank database, the result reveals
      high degree of homology in sequence and organization pattern of domain with
      metalloproteinase/disintegrin gene family of other snake species. Compared with
      the alignment of amino acid sequence of metalloproteinase/disintegrin member,
      hypervariable regions of this member were revealed, besides they share higher
      homologous in the zymogen domain. It suggests that the hypervariable regions are
      the counterparts directly suitable for interacting with different domain of
      receptors, different receptors or substrates.

PMID- 15969022
TI  - [Kinetic models for the effect of temperature on batch glutathione fermentation
      by Candida utilis].
AB  - Glutathione (L-gamma-glutamyl-L-cysteinylglycine), one of the major non-protein
      thiol compounds, is widely distributed in living cells and plays an important
      role in maintaining the normal redox environment of cells as an antioxidant. In
      the production of glutathione by fermentation, temperature is one of the most
      important environmental factors that affect the yield and the productivity of
      glutathione. Here the effect of temperature, varied from 24 degrees C to 32
      degrees C, on the batch fermentation of glutathione in a 7 L stirred fermenter by
      Candida utilis WSH 02-08 was investigated. It was found that cell growth was
      hastened along with the increase of temperature. The maximum dry cell weight was
      achieved approximately 16 g/L under various temperatures, as soon as the glucose
      was exhausted. The effect of temperature on glutathione production was different
      from that on cell growth: the lower the temperature, the higher the glutathione
      production, i.e. the maximum glutathione concentration at 32 degrees C (235 mg/L)
      was only 75% and 64% of that at 30 degrees C and 26 degrees C, respectively. The
      maximum average specific growth rate (0.13 h(-1)) was achieved at 30 degrees C
      while the maximum glutathione concentration (366 mg x L(-1)) and the maximum
      intracellular glutathione content (2.3%) were obtained at 26 degrees C.
      Therefore, the optimum temperatures for cell growth and glutathione production
      are quite different in the batch fermentation. A modified Logistic equation was
      successfully applied to estimate the kinetics of cell growth. The maximum
      specific growth rate and the substrate inhibition constant, calculated from this
      equation, were both increased along with the temperature. In addition, the
      glutathione fermentation by C. utilis WSH 02-08 under various temperatures was
      proven to be a partial growth-associated process by estimating the process with
      the Luedeking-Piret equation. Based on the estimated parameon the estimated
      parameters, the effect of temperature on the kinetics of cell growth was further
      studied. An equation, dX / dt = [0.0224(T + 1.7)]2 X(1-X/Xmax) / 1 + S/ {8.26 x
      10(6) x exp [-31477/R/(T+273)]}, was developed and applied to interlink the
      relationship between biomass concentration and temperature as well as substrate
      concentration in the batch glutathione fermentation. The experiment results
      showed that this model could predict the growth pattern very well.

PMID- 15969023
TI  - [Protoplast isolation and transformation of Exserohilum turcicum].
AB  - Northern corn leaf blight, caused by the fungus Exserohirum turcicum Pass.
      (Leonard and Suggs), is one of the major diseases in most corn-growing areas of
      the world. Research on gene tagging of E. turcicum has been limited due to the
      lack of an efficient transformation system. Since E. turcicum produces and
      accumulates melamin in cell walls during vegetative growth, it is difficult to
      efficiently isolate its protoplast. To isolate the protoplast of this pathogen
      with a high frequency, the effects of cell wall degradation enzymes, including
      beta-1,3-glucanase (Fungase, Funcelase, Novozyme and Glucanex) and beta
      glucuronidase (Driselase, Uskizyme and Kitalase), enzyme concentrations,
      combinations, strains and medium on the isolation frequency were tested. The
      isolation frequencies were high enough for transformation when the combinations
      of (Kitalase + Glucanex + Driselase), (Kitalase + Glucanex) or (Kitalase +
      Uskizyme) were used. Moreover, the isolation frequencies of protoplast were
      significantly affected by the cultural morphologies of strain and the growth
      stage of mycelia. Among the plasmids tested, only plasmid pAN71 is efficient for
      transformation of E. turcicum. This result will provide some useful information
      for gene tagging of E. turcicum and other species in Exserohirum.

PMID- 15969024
TI  - [Cloning and sequence analysis of MYB transcriptional regulator SmP gene of
      Saussurea medusa Maxim].
AB  - A full-length cDNA encoding a MYB-related regulatory gene was isolated from a
      cDNA library prepared from mRNAs of the red line callus of S. medusa by TD-PCR.
      The cDNA, designated SmP, is 969 nucleotides long and has an open reading frame
      of 771 bp with a deduced amino acid sequence of 256 residues. The putative
      protein of SmP has two typical conversed R2R3-Myb DNA-binding domains in N
      terminal and displays a rather high degree of similarity to OsMYB from rice and
      LBMI from tobacco, showing 73% and 70% identity within the DNA-binding domains.
      However, the C-terminal domain of the SmP protein does not show obvious
      similarity to any other known protein sequence. It is rich in hydrophilic amino
      acids, especially in serine residues (18.38%), partly organized in homopolymeric
      stretches, a feature often found in activation domain of transcription factors.

PMID- 15969025
TI  - [Study on the culture of crown gall from Panax quinquefolium and the prouction of
      its secondary metabolites--Ginsenosides Re and Rg1].
AB  - It was clearly demonstrated that T-DNA of Agrobacterium tumefeciens Ti plasmid
      was integrated into the cells of crown gall in our experiment. This paper
      reported the influences of some kinds of physical-chemistry factors on the growth
      of crown gall of Panax quinquefolium and the production of its main active
      compounds--ginsenoside Re and ginsensoside Rg1. The results showed that White
      medium was the best one for ginsensoside Rg1 accumulation (0.095%) among the six
      media, but ginsensoside Re accumulation (0.194%) was the highest on the MS
      medium; The highest contents of ginsensoside Re (0.147%) and ginsensoside Rg1
      (0.061%) were on the culture 36d and 32d after innoculum respectively; The
      optimum pH was 5.6 for ginsensoside Rg1 synthesis(0.054%), and 5.8 for
      ginsensoside Re synthesis(0. 184% ); The contents of ginsensoside Re and
      ginsensoside Rg1 was the highest in the inoculum of 4 g and 2 g/flask (FW)
      respectively. The result also indicated that the concentration of inositol in
      0.05 g/L could obviously promote ginsensoside Re synthesis (0.182%), and in 0.30
      g/L for ginsensoside Rg1 (0.055%).

PMID- 15969026
TI  - [Expression of recombinant plasmid pcDNA3.1/P12X3C with multi-genes of foot-and
      mouth disease virus in BHK-21 cells].
AB  - In order to obtain the gene P12X3C of Foot-and-Mouth Disease Virus (FMDV) that
      includes full length P1, 2A, 3C and a part of 2B, the site mutation strategy was
      used. After being digested by Kpn I and Xba I respectively, the gene P12X3C was
      cloned into the pcDNA3.1 (+) expression vector. The recombinant plasmid was
      checked by restriction enzyme analysis and nucleic acid sequencing, and then
      named pcDNA3.1/P12X3C. Further, BHK-21 cells was transfected with pcDNA3.1/P12X3C
      by using lipoid. The proteins of Foot-and-Mouth Disease Virus, which were
      expressed in BHK-21 cells, were confirmed by sandwich-ELISA and fluoroscopy. The
      result shows the gene P12X3C is cloned into eukaryotic expression plasmid, and
      the recombinant eukaryotic expression plasmid pcDNA3.1/P12X3C could express
      proteins of Foot-and-Mouth Disease Virus in BHK-21 cells, which have
      immunocompetence. This study demonstrates that delivery of a recombinant
      eukaryotic expression plasmid containing P12X3C coding regions results in the
      assembly of FMDV capsid structures, which will offer experimental base to DNA
      vaccine of FMDV.

PMID- 15969027
TI  - [Oxidative refolding of proteins].
AB  - The mechanism of oxidative refolding of proteins was elucidated in more detail
      from the intensive and extensive studies in the past decades. 1. Most of the
      proteins examined so far proceed oxidative refolding via multiple pathways rather
      than a single and specific pathway. This is consistent with the folding energy
      landscape theory. 2. It is the native interactions rather than the non-native
      interactions that direct the folding process. This is not necessarily
      incompatible with the importance of the non-native disulfide intermediates in the
      bovine pancreatic trypsin inhibitor (BPTI) pathway, which are just a chemical
      necessity in the intramolecular arrangement to facilitate native disulfide
      formation. 3. Based on the BPTI refolding it was suggested that disulfide bonds
      have a stabilizing effect on the native state without determining either the
      folding pathway or the final three-dimensional structure of the protein. This
      point of view is not applicable to other proteins. Studies on the refolding of
      prochymosin unequivocally demonstrated that the formation of native disulfides is
      the prerequisite to the recovery of the native conformation. It is more likely
      that the interdependence between the native disulfide formation and the formation
      of native structure is a general rule. 4. At the early stage of oxidative
      refolding disulfide formation is essentially a random process, with the progress
      of refolding further disulfide formation is increasingly dependent on the
      conformations of the intermediates. Enhancing the renaturation yield of
      recombinant proteins is a major challenge in biotechnology. In addition to
      aggregation, the formation of species with mispaired disulfide bonds is a leading
      cause of decreased yield. Progress in understanding the mechanism of oxidative
      refolding has provided insight into how to solve this problem. As described
      above, at the later stage of refolding disulfide formation depends on the
      conformations of intermediates. The intermediates with native-like and flexible
      structure favourable for native disulfide formation and correct refolding are
      productive intermediates, while the unproductive intermediates tend to adopt
      stable conformations, which render the thiol groups and disulfide bond(s)
      inaccessible and further folding unfavourable energetically. Therefore, the
      principle to enhance the renaturation yield of disulfide-containing proteins is
      to cause the productive intermediates to predominate by destabilizing the
      unproductive intermediates. To approach this, alkaline pH, low temperature,
      labilizing agents, protein disulfide isomerase and its analogues and alteration
      of primary structure have been proved useful to adjusting the structure of the
      unproductive intermediates so as to facilitate thiol/disulfide interchange and in
      turn the native disulfide formation. The prospects for the oxidative refolding of
      proteins both in basic and applied researches are discussed in this review
      article.

PMID- 15969028
TI  - [Epigenetic modifications and its impact on animal cloning].
AB  - Despite recent successes in cloning various mammals and amphibians, the low
      efficiency of animals production and abnormal symptoms in many cloned animals are
      crucial problems in cloning technology. To overcome these problems, scientists
      focus on mechanisms of cloning. A possible cause of the low success frequency of
      cloning is the insufficient dedifferentiation and the inadequate reprogramming of
      the high differentiated adult somatic nucleus in enucleated oocytes, which caused
      by incomplete methylation and premature de novo remethylation of donor DNA. In
      cloned embryos the methylation level is higher than normal embryos, and this may
      cause aberrant expression of several important genes, especially imprinting
      genes. Study on these mechanisms is very important to improve the rate of
      successful cloned animals.

PMID- 15969029
TI  - [Study on relationship between length of homologous sequences and chromosomic
      recombination rate in Saccharopolyspora erythraea].
AB  - In order to study the relationship between lengths of homologous fragments and
      chromsomic recombination rate in Saccharopolyspora erythraea, three homologous
      sequences, with mutant loci and different flanking sequences, (26bp + 27bp),
      (500bp + 576bp) and (1908bp + 1749bp), were synthesized by chemical reaction or
      PCR amplification, and cloned into pWHM3 to construct homologous recombination
      plasmids, pWHM1113, pWHM1116 and pWHM1119. When the plasmids were transformed
      into protoplast of Saccharopolyspora erythraea A226 under PEG mediated, on an
      average 30, 69 and 170 transformants grew on each plate for the three plasmids
      respectively, but chromosomic integration frequency were 0, 2% and 19% among
      corresponding transformants. Both pWHM1116 and pWHM1119 could take double
      crossover recombination, and exchange the mutant loci in the chromosome. It was
      concluded that when the flanking sequences were equal or more than (500bp +
      576bp), they could take effective single and double recombination with
      Saccharopolyspora erythraea chromosome.

PMID- 15969030
TI  - [Expression of a human single-chain Fv antibody against HBsAg in Pichia
      pastoris].
AB  - To express and secrete native HBscFv (anti-HBsAg single-chain Fv) in P. pastoris,
      HBscFv was amplified from plasmid pGEM-HBscFv, and then sub-cloned into
      expression vector pPICZalphaA. The resulting plasmid pPIC-HBscFv was linearized
      and transformed into P. pastoris GS115. The recombinant Pichia strains,
      identified by direct PCR and Zeocin-resistant screening of Pichia transformants,
      were cultured and induced with methanol. It was found that recombinant HBscFv,
      lead by alpha-factor, could be secreted into the culture supernatant to a level
      of 80mg/L. The bioactivity of Pichia produced HBscFv was confirmed by indirect
      ELISA, which also suggested that the bioactivity of HBscFv in the culture
      supernatant reached its peak in 72h and decreased in the late-stage of the
      induction. PAS staining suggests that HBscFv produced by yeast is poorly
      glycosylated or none-glycosylated protein.

PMID- 15969031
TI  - [Safety, stability and immunogenicity of an oral DNA vaccine against Newcastle
      disease].
AB  - Mice and 3-day-old chickens were orally inoculated with the recombinant
      attenuated Salmonella typhimurium strain ZJ111 carrying pcDNA3-F expression
      plasmid encoding the fusion protein of Newcastle disease virus (NDV). The results
      showed that ZJ111/pcDNA3-F was relatively safe. The recombinant plasmid pcDNA3-F
      was stable within the host stain ZJ111 in vitro and in vivo as shown by
      restriction enzyme analysis and PCR identification of the F gene. In an
      experimental vaccination study, 3-day-old chickens were orally immunized with
      ZJ111/pcDNA3-F with a dose of 108 cfu per chicken and boosted two weeks later. At
      week 4 post boosting, all chickens were challenged with a lethal dose of a
      virulent NDV strain F48 E9. The results showed that oral vaccination with
      ZJ111/pcDNA3-F induced stronger humoral and cellular immune responses than
      intramuscular immunization with naked pcDNA3-F plasmid. It also exhibited higher
      protection rate than the latter (66.7% vs 50%). This study indicates that the DNA
      vaccine using attenuated Salmonella typhimurium as delivery carrier had good
      safety, stability and immunogenicity and exhibited good potential of low cost and
      convenience for poultry disease control.

PMID- 15969032
TI  - [Isolation and identification of reprogramming genes related to the development
      of the rabbit reconstructed embryos].
AB  - By the method of single preimplantation embryos differential display polymerase
      chain reaction (SPEDDRT-PCR), 25 reprogramming cDNA fragments were obtained from
      single 2-cell, 8-cell embryos and blastula. After cloning and sequencing, five of
      them were identified by reverse-Northern and characterized with stage-specific
      expression during reconstructed embryo development. This results will help to
      isolate full length reprogramming genes and study their function during embryonic
      development.

PMID- 15969033
TI  - [Construction and biological activity study of human osteoprotegerin expressing
      adenoviral system].
AB  - Using the isolated total RNA from osteosacoma cell line MG63, the cDNA encoding
      human OPG was amplified by RT-PCR. A recombinant adenoviral vector carrying cDNA
      of OPG was constructed and OPG expression in mouse myoblast C2C12 cells was
      confirmed by Western blot and ELISA. The secreted expression of OPG protein
      persisted more than 6 weeks in vitro, and the growth of C2C12 cells infected by
      recombinant adenoviral were in good state. Osteoclasts derived from mouse bone
      marrow cells infected with recombinant adenoviral made less number of TRAP
      positive cells and resorption pits formed on dentine slices.

PMID- 15969034
TI  - [Expression of xylanase gene xynA from Streptomyces olivaceoviridis A1 in
      Escherichia coli and Pichia pastoris].
AB  - The gene xynA encoding xylanase was cloned from Streptomyces olivaceoviridis A1.
      The xynA with and without origin signal peptide sequence were fused behind pel B
      signal peptide in the plasmid pET-22b(+) respectively, then transfered into the
      host E. coli. The xylanase expressed in E. coli had normal bioactivity. Further,
      the xynA without origin signal peptide sequence was cloned into the plasmid pPIC9
      under the control of AOX1 promoter and introduced into the host Pichia pastoris
      by electroporation. The results of SDS-PAGE and activity assay of the xylanase
      expressed by recombinant P. pastoris showed that the xynA had been overexpressed
      and secreted, and the xylanase expressed had normal bioactivity. The expression
      level of xylanase in recombinant P. pastoris exceeded 0.2mg/mL in shake culture.

PMID- 15969035
TI  - [Induction and culture of hairy boots in Phytolacca esculenta and its saponin
      production].
AB  - Hairy roots appeared in vitro 20 days after inoculation of Phytolacca esculenta
      leaf explants with the strain of Agrobacterium rhizogenes R1601. The frequency of
      leaf explants transformed by R1601 was up to 70%. Hairy roots can be incited
      directly from the veins of explants or via callus. Hairy roots induced by R1601
      grew rapidly on medium MS without hormone and were 85.6% higher in respiration
      rate than control roots. Transformation was confirmed by opine detection and the
      amplification of rol B and rol C genes from the hairy roots of P. esculenta. The
      total saponin content in hairy roots of P. esculenta was about 1.54 times as much
      as in natural roots whereas polysaccharides content was about 70% times as much
      as in the natural roots.

PMID- 15969036
TI  - [Secreted expression of Bacillus pumilus xylanase gene in Pichia pastoris and
      study on enzymatic properties].
AB  - The endo-1,4-xylanase gene from Bacillus pumilus HB030 was cloned into the Pichia
      pastoris expression vector, pPIC9k, the recombinant plasmid was named pHBM220.
      The digested recombinant plasmid pHBM220 was transformed into Pichia pastoris
      KM71, GS115, SMD1168, respectively. The recombinant Pichia pastoris KM71
      (pHBM220), GS115 (pHBM220), SMD1168 (pHBM220) secreted functional endo-1,4
      xylanase, and the enzymatic activities reached 10.80IU/mL, 11.63IU/mL, 9.68IU/mL,
      respectively. The temperature and pH optimum for the recombinant xylanase were 60
      degrees C and pH5.5, respectively.

PMID- 15969037
TI  - [Orange fluorescent protein--modification of green fluorescent protein GFPxm].
AB  - Recently, we have reported a new gfp gene isolated from Aequorea macrodactyla.
      The protein purified from expressed E. coli exhibited an excitation peak at 476
      nm and an emission peak at 496 nm. However, the drawback of only maturing to
      fluorescence at low temperature limited its applications. In this paper, we
      further describe twelve mutants of GFPxm. Seven mutants produced enhanced
      fluorescence when expressed in E. coli at higher temperature (37 degrees C).
      After six hours of induction at 25 degrees C, 32 degrees C and 37 degrees C
      respectively, the relative fluorescent intensities of GFPxm16, GFPxm18 and
      GFPxm19 were higher than that of EGFP, moreover GFPxm16 and GFPxm163 could
      preserve high fluorescent intensity even expressed at 42 degrees C. Four mutants
      of the seven could reach high expression level in three kind of mammalian cells.
      Another 6 mutants had red-shift of excitation-emission maxima, and longest
      excitation-emission maxima were 514nm and 525nm. Another three mutants had two
      excitation peaks, and one mutant had only one UV-excitation peak. The most
      exciting result is the mutant of OFPxm with orange color. The mutant has an
      excitation peak at 509 nm and an emission peak at 523nm. 523nm is yellowish green
      but the protein is orange observed by eyes. The mutant could reach high
      expression level and matured at higher temperature but the fluorescent intensity
      was comparatively low because of low quantum yield.

PMID- 15969038
TI  - [Fusion expression, purification and bioactivity assay of CpTI in Escherichia
      coli].
AB  - CpTI (Cowpea Trypsin Inhibitor) is a widely used insect resistance gene in the
      plant genetic engineering for its high insecticidal activity and the minimal
      ability of the insects to evolve resistance to it. To facilitate the safety
      assessment of genetically modified foods (GMFs) with CpTI protein, we need to
      produce gram quantities of this protein in microbes. With the pGEX fusion
      expression system, we expressed the GST-CpTI protein in E. coli BL21, which
      accounted for approximately 40% of germ proteins. By Glutathione Sephrose 4B
      affinity chromatography, GST-CpTI was obtained with the purity up to 90%.
      Overnight incubate the fusion proteins with Thrombin protease, we got the CpTI
      proteins cleavage of GST tag. Both of the GST-CpTI and CpTI proteins showed
      notable trypsin inhibitor activity. Immunization of rabbits with purified fusion
      protein generated high titer antibodies (> 20000), measuring by ELISA. Western
      Blotting also showed specific Ag-Ab binding band between the antiserum and the
      CpTI proteins no matter in the whole supersonic germ proteins or purified from
      the column. All these made a good ground for the further safety assessment of
      CpTI protein.

PMID- 15969039
TI  - [Study of the expression membrane protein LASS2].
AB  - A human membrane protein LASS2 (Homo sapiens longevity assurance homologue 2 of
      yeast LAG1), which has important physiologic functions, was expressed in three
      different expression systems. Only the LASS2 protein carboxyl terminal
      hydrophilic fragment could be expressed in the prokaryote expression system and
      its polyclonal antibody was produced. The full length of LASS2 protein could be
      expressed successfully in both eukaryotic in vitro translation system and
      Bacuvirus expression system: Bac-to-Bac system. SDS-PAGE analysis revealed that
      the molecular weight of expressed product of LASS2 was about 28 kD. The product
      was also proved by Western blot. This recombinant LASS2 protein was purified by
      metal affinity resin and the purity is above 90%.

PMID- 15969040
TI  - [Biotransformation of benzene to cis-1,2-dihydroxycyclohexa-3,5-diene using
      recombinant Escherichia coli JM109 (pKST11)].
AB  - Cis-1,2-dihydroxycyclohexa-3,5-diene (DHCD) can be used as a valuable chiral
      intermediates for applications in pharmaceuticals, aerospace, electrical and fine
      chemical industries. By on-line detection of toluene dioxygenase (TDO) activity
      in whole recombinant Escherichia coli JM109 (pKST11) cells that harbored TDO gene
      under a tac promoter, effects of IPTG and various benzene addition strategies on
      bioransformation of benzene to DHCD were investigated. When IPTG was used at the
      beginning of fermentation, the growth of cells was inhibited and TDO activity
      only maintained for 4 hours while same experiments with addition of IPTG at 6h or
      8h generated TDO activity for 18 hours. Suitable induction time for IPTG was in
      the cell logarithmic growth phase and 0.5 mmol/L IPTG was sufficient for inducing
      maximum TDO activities. Benzene strongly inhibited the activity of TDO which
      catalyses the conversion of benzene to DHCD. It was found that both cell growth
      and TDO activity was remarkably inhibited by feeding of benzene vapor, only 7.5
      g/L DHCD was obtained. While the benzene inhibition effect was ameliorated by two
      liquid phase culture fermentation in which liquid paraffin was used as second
      phase in the broth. Using different initial ratios of paraffin to benzene in fed
      batch culture, DHCD contents were increased to 22.6 g/L, which was 3-fold more
      compared with that in benzene vapor culture. A further improvement of DHCD
      production was achieved when the mixture of liquid paraffin and benzene was added
      continuously by peristaltic pump, the DHCD contents were increased to a final
      concentration of 36.8 g/L. It was proven that the key to improving DHCD
      production by recombinants is to prolong TDO activity in cells, which can be
      achieved by using suitable addition benzene strategies.

PMID- 15969041
TI  - [Quantitative studies of the production phase in rHSA fermentation].
AB  - The model equations of the production phase of rHSA fermentation were derived on
      the base of both elemental balance and metabolic balance, then the unknown
      parameters of the model were estimated by multivariable optimization. The
      possible reasons of discrepancy of production rate between different period of
      fermentation were discussed. The model could preferably described the relations
      between different macroscopic reaction rates of the process and keys for the high
      efficiency expression of HAS were deduced.

PMID- 15969042
TI  - [Fed-batch fermentation of Escherichia coli that express fab fragment of anti
      HBsAg].
AB  - To develop a fed-batch fementation process of E. coli TOP10 containing a
      recombinant plasmid pBAD/HBs Fab. Cells were grown in semi-defined medium at 37
      degrees C, and the feed operation using glycerol as carbon source was performed
      when dissolved oxygen increased. When the target cell concentration reached to
      64g/L, arabinose was added to a final concentration of 0.02%. Cells were grown
      for another 5h with the culture temperature decreased from 37 degrees C to 30
      degrees C. In the whole process, cell growth was monitored by measuring OD600 of
      samples taken at 1/2h intervals and the dissolved oxygen was kept above 30%.
      After the fementation, E. coli pellets were collected for purification of Fab
      protein. The specificity of Fab protein was confirmed by Western blot, and
      binding activity to HBsAg was verified by Dot blot. Cell concentration we got is
      96g wet bacteria per liter, the Fab protein is about 6% of total protein of the
      host, that is 80mg per liter. Stable fermentation parameters were obtained for
      fermentation to improve productivity of the Fab protein. The Fab protein was
      produced in the form of soluble biologically active protein, it's better than
      inclusion bodies from which biologically active protein can only be recovered by
      complicated and costly denaturation and refolding process.

PMID- 15969043
TI  - [2-dimensional gel electrophoresis on protein patterns from suspension cultures
      of Taxus cuspidate induced by SA].
AB  - The permeability of cell membrane was enhanced by exogenous SA in the culture of
      Taxus cuspidata. Nuclei condense and fragments were observed in some cells by
      using fluorescent microscope, and the degraded chromosomal DNA was observed by
      using agarose gel electrophoresis. The changes in soluble proteins of the
      suspension cultures of Taxus cuspidata induced by salicylic acids were analyzed
      by using two-dimensional polyacrylamide gel electrophoresis. Comparing with the
      control, seven new protein spots were found and six protein spots were not found
      in the cultures grown with SA at 48h. The results obtained showed that SA could
      induce the expression of some special proteins that might be related with the
      action of SA in the suspension cultures of Taxus cuspidata.

PMID- 15969044
TI  - [Studies of enzymatic synthesis of biodiesel].
AB  - Biodiesel, an alternative diesel fuel, fatty acid alkyl ester, is made from
      renewable biological sources such as vegetable oils and animal fats. Two
      processes for biodiesel synthesis, enzymatic lipase catalytic esterification from
      fatty acid and transesterification from oils and fats, was investigated. The
      effects of various lipases, enzyme amount and purity, solvent, water absorbent,
      inhibition of short chains alcohol, specificity of substrate, molar ratio of
      substrate on esterification were studied in detail. The esterification degree
      with the optimal parameter and process can reach up to 92%. The purity of
      biodiesel obtained by separation and purification is up to 98%, and the half-life
      of the immobilized lipase for the esterification process can be up to 360hr,
      Moreover, the preliminary studies of the transesterification including the amount
      of methanol and mode of adding methanol into reaction system were made. The
      transesterification degree with adding methanol stepwise can reach 83%.

PMID- 15969045
TI  - [High expression and characterization of human parathyroid hormone in Escherichia
      coli].
AB  - Human parathyroid hormone (hPTH) was highly expressed in Escherichia coli by
      inserted the synthesized whole hPTH cDNA into the vectors pBV220 and pET22b.
      After expression and disruption, the purified product was acquired through cation
      exchange chromatography and reverse phase chromatography. From the results of N
      terminal sequencing and MALDI-TOF-MS analysis the recombiant prtein was
      indentified as intact hPTH. In in vitro Bioassays the recombinant hPTH stimulated
      adenylate cyclase as the standard did. In ovariectomized rats the recombinant
      hPTH markedly increased the femoral bone mass and bone mineral density.

PMID- 15969046
TI  - Construction of recombinant adenoviral vector overexpressing human HIF-1alpha
      gene.
AB  - Hypoxia inducible factor 1 (HIF-1) is a heterodimeric transcription factor that
      plays an important role in oxygen homeostasis. In response to low level of
      oxygen, subunit HIF-1alpha expression is upregulated and transactivates its
      target genes essential for energy metabolism, erythropoiesis and vascular
      development. HIF-1alpha is thought to be able to protect hypoxic cells from
      apoptosis or necrosis under ischemic and anoxic conditions, the major trauma
      factors that affect the recovery of brain and spinal cord injury. Here we report
      the construction of recombinant adenovirus vector overexpressing HIF-1alpha
      intended for gene therapy against desired neuronal injuries. The recombinant
      vector could be packaged and yielded significantly high viral titers at 2 x
      10(13) CFU in HEK293T cells and good expression levels of HIF-1alpha when
      superinfected in Hela cells.

PMID- 15969047
TI  - [Expression of phytase gene in Bombyx mori].
AB  - Phytase gene of Aspergillus niger 963 was cloned into baculovirus transfer
      vector. DNA of the recombinant vector was co-transfected with Bm-BacPAK6 DNA into
      BmN cells, and recombinant virus was selected by plaque assays. The recombinant
      virus was identified by Dot blot and Southern-blot with the specific probe for
      phytase gene. Phytase gene was expressed in silkworm larvae and pupae. The
      expression product was 1.43 g/L haemolymph for silkworm larvae and 1.90 g/L
      haemolymph for pupae, respectively. The enzymic characteristicses of phytase
      expressed in baculovirus-expression system were studied in this paper.

PMID- 15969048
TI  - [The preparation of fructose-modified chitosan microcarrier and culture of
      primary rat hepatocyte].
AB  - Crosslinked chitosan microcarries were prepared by the reaction of glutaraldehyde
      with fructose-modified chitosan. Various factors that influence the preparation
      were studied and the reaction conditions were optimized. Morphology of rat
      hepatocyte cultured on chitosan microcarriers was observed using phase contrast
      microscopy and scanning electron microscope, the metabolic activity was measured.
      Rat hepatocytes cultured on chitosan microcarrier retained the spherical shape as
      they have in vivo and had high metabolic activity. Fructose can enhance the
      metabolic activity of hepatocytes and fructose-modified chitosan microcarrier is
      a promising scaffold for hepatocytes attachment, which can be used in
      bioartificial liver support system.

PMID- 15969049
TI  - [Using single primer PCR to amplify the orf25 gene fragment related to plant male
      sterility in Salicornia europaea].
AB  - The gene orf25 encodes functional protein that may play an important role in
      plant fertility control in nature. To clone the orf25 from Salicornia europaea
      Xinjiang into a T-vector, a single designed primer was used to amplify 1.7kb cDNA
      fragment with RT-PCR. Sequence analysis reveals that the cloned fragment contains
      entire orf25 coding region with 98%, 95%, 92% and 88% identity to that of orf25
      from Beta vulgaris, Nicotiana, wheat and maize mitochondrion, respectively. This
      analysis suggests that orf25 gene is highly conserved in terms of evolution in
      plant; and it also suggests that wild plant Salicornia europaea contain a male
      sterility gene similar to crops that is of great importance in improvement of the
      breed of crop.

PMID- 15969050
TI  - [Recent advances in the study of Vitreoscilla hemoglobin(VHb) and related
      proteins - cloning, expression and physiological actions in heterologons hosts
      and in transgenic tobacco plants].
AB  - The first bacterial hemoglobin(VHb) was found in a strictly aerobic bacterium,
      Vitreoscilla strain C1, occurring in marshes low in oxygen, but rich in organic
      matter. The hemoglobin gene is induced under low oxygen tension and may amount to
      20 times as high. The expression of VHb promotes cell growth, protein
      biosynthesis and primary and secondary metabolism of the host cells, because the
      increased intracellular oxygen accelerates both the function of respiratory chain
      and terminal oxidases. The serial action of increased oxygen concentration is
      elucidated through yeast two hybrid system and a model is proposed. In addition,
      novel globin proteins known as flavohemoglobins have been isolated from various
      procaryotes and eucaryotes, with a N-terminal similar to VHb and C-terminal with
      reductase activity. Primary study shows that flavohemoglobin proteins exhibit
      similar function as VHb and also protection effect to nitrosative stress. Further
      work is needed to learn more about the physiology of these flavohemoglobins. The
      most remarkable physiological effects of VHb are exihibited in transgenic tobacco
      plants, including accelerated seed germination and growth in plant, increased
      synthesis of chlorophyll and dry weight. Without doubt, these effects are brought
      about through the increased oxygen supply to plant cells. It is deemed that VHb
      transgenic tobacco is a forerunner for transgenic crops and VHb may be a valuable
      route for staple seed crops.

PMID- 15969051
TI  - [Advances in apolipoprotein A- I and it's anti-atherosclerosis properties].
AB  - Human apolipoprotein A- I, the major protein component of high density
      lipoproteins and the main activator of the enzyme lecithin: cholesterol
      acyltransferase, defines the structure and stability and functions of HDL. It is
      clearly demonstrated that high concentration of the apoA- I not only inhibits the
      initiation and progression of atherosclerosis, but also makes the preexisting
      atherosclerotic lesions regress. This review gives an overview of the apoA- I
      structure, production, relation between apoA- I and HDL, and several mechanisms
      of the apoA-I anti-atherosclerosis. These mechanisms include directing excess
      celluar cholesterol from the peripheral tissues to the liver in reverse
      cholesterol transport, inhibiting oxidative modification of LDL, and modulating
      inflammatory responses to favour vasoprotection.

PMID- 15969052
TI  - [Over-expression in Escherichia coli and purification of nucleocaspid and
      membrane protein of SARS coronavirus].
AB  - Genes encoding nucleocaspid (N) and membrane (M) protein of SARS coronavirus were
      obtained by RT-PCR and were cloned into expression vector pET22b and pBV222. DNA
      sequencing showed that the genes cloned from a patient in Beijing were identical
      to the gene sequences from reported Toronto strain. The genes were over-expressed
      in E. coli either as inclusion body or as soluble form. The recombinant proteins
      were purified by ion-exchange, or ion-exchange followed by metal chelate affinity
      chromatography. The recombinant N protein was demonstrated highly antigenic and
      could be employed as antigen to detect SARS antibodies in ELISA system for SARS
      diagnosis.

PMID- 15969053
TI  - [Expression of gene aiiA carrying the promoter of gene cry3Aa in Bacillus
      thuringiensis].
AB  - N-acyl-homoserine lactones (AHLs), are widely conserved signal molecules present
      in quorum-sensing systems of many Gram-negative bacteria. AHLs molecules mediate
      the expression of virulence genes of a range of bacterial pathogens. Recently, it
      has been reported that AiiA protein, which widely exists in Bacillus species, can
      inactivate the AHLs by hydrolyzing the lactone bond of AHLs, thus attenuate the
      diseases caused by the expression of virulence genes of bacterial pathogens.
      Bacillus thuringiensis, a type of Gram-positive bacteria, has been used
      extensively as a microbial insecticide in the last few decades. However, most of
      important insecticidal B. thuringiensis strains have not been exploited for
      bacterial disease control because they usually do not produce antibiotics that
      are effective against bacteria and fungi. The discovery of AiiA protein in B.
      thuringiensis shows the application potential of B. thuringiensis on biocontrol
      against bacterial diseases. In this study, in order to construct the B.
      thuringiensis recombinant strain that has high expression of AiiA protein, the
      promoter of insecticidal crystal protein coding gene cry3Aa of B. thuringiensis
      was selected. The promoter of gene cry3Aa is a non-sporulation promoter, it
      promotes the transcription earlier and longer than the promoters of other cry
      genes. The promoter of AiiA protein coding gene aiiA was replaced with the
      promoter of gene cry3Aa by overlapping PCR, resulting fusion gene pro3A-aiiA. The
      gene pro3A-aiiA was inserted into shuttle vector pHT304 at site BamH I / Sph I ,
      resulting recombinant plasmid pBMB686. The plasmid pBMB686 was introduced into B.
      thuringiensis acrystalliferous strain BMB171, the resulting strain BMB686 had a
      higher and more stable expression level of protein AiiA comparing with the
      parental strain BMB171. Furthermore, the strain BMB686 exhibited stronger ability
      of AHLs inactivation and much more effective restraint to the potato's soft rot
      disease caused by Erwinia carotovora than those of the parental strain BMB171.
      From these results, it was concluded that the B. thuringiensis strain harvesting
      the fusion gene pro3A-aiiA may be utilized in the future to control bacterial
      diseases which are mediated by the AHL quorum-sensing signals.

PMID- 15969054
TI  - [Gene cloning, soluble expression and activity analysis of rSEA].
AB  - The superantigen,such as staphylococcal enterotoxins, had been identified as
      possible anti-cancer molecules in many reports. In this paper, we cloned the entA
      gene encoding Staphylococcal enterotoxin A from the genomic DNA of Staphylococcus
      aureus(ATCC13565) by PCR, the sequence cloned was accordance with that reported
      in Genebank. The entA gene could be expressed effectively after inserted into
      plasmid pET-22b( + ), The rSEA was expressed as inclusion bodies when induced by
      IPTG at 37 degrees C and became soluble after induced at low temperature, the
      soluble part is about 55% of total rSEA products. Only one band was detected by
      western-blotting in expression product of BL-21 (DE3) with pET-SEA. The soluble
      rSEA was purified by Ni2+ chelating sepharose column. No other protein except
      rSEA was seen in SDS-PAGE gel stained by both Coomassie brilliant blue and silver
      salt, which showed that the rSEA was purified effectively. Homology modeling of
      rSEA determined the structure change was conducted, which indicated there was no
      apparent structure change between rSEA and native SEA. This result was also
      confirmed by proliferation assay of PBMC, for the rSEA could induced
      proliferation of PBMC as effectively as native SEA. The increasing anti-tumor
      activity of rSEA was also detected after the spleen cell activated in vivo by
      rSEA, which was accordance with others reports. This work paved the way for the
      further study of anti-cancer with rSEA.

PMID- 15969055
TI  - [Establishment of gene transduction system in geldanamycin producer -
      Streptomyces hygroscopicus 17997 and its application for gene disruption
      experiment].
AB  - Streptomyces hygroscopicus 17997 produces the antiviral and antitumor ansamycin
      antibiotic, geldanamycin. Studies on geldanamycin biosynthetic pathway will
      provide good tools for genetic manipulation of the antibiotic-producing strain to
      improve the productivity or to facilitate making novel geldanamycin analogs. The
      structural similarities between geldanamycin and ansamycins such as rifamycin or
      ansatrienin suggest that both geldanamycin and ansamycins has a closely related
      pathways of biosynthesis and that biosynthetic system for geldanamycin is similar
      to the one of type I polyketide synthase (PKS) enzyme system. To explore the
      possible PKS genes involved in geldanamycin biosynthesis, the degenerate primers
      were designed according to the conserved sequence of KS-AT region from
      erythromycin and oleandomycin type I PKS genes. Cosmids containing multiple PKS
      genes (pCGBK2,4,6,10,11,18) were obtained by hybridization with the PCR products,
      which were amplified from S. hygroscopisus 17997 genomic DNA. The designed
      primers above were used for PCR. Development of a Streptomyces temperate phage
      phiC31-derivative KC515( tsrR) transduction system was carried out for
      identification of cosmids containing the PKS gene related to biosynthesis of
      geldanamycin. Several factors, mainly the Ca2+ and Mg + concentrations in
      different culture media affecting the frequency of gene transfection, were
      optimized .Transfection efficiency could reach up to 10(3) /microg DNA on YMG
      medium supplemented with 10mmol/L MgSO4. Reversely, the transfection efficiency
      decreased when YMG medium was supplemented with 30mmol/L MgSO4. Gene transfection
      system based on the integration-defective phage KC515 had been established for S.
      hygroscopicus17997. Recombinant phages (ph111, 258, 287, 116, 105) were
      constructed by insertion of the homologous to PKS gene fragments into the KC515
      phage vector. Gene disruption experiments were performed by transduction of
      recombinant phages into S. hygroscopicus 17997 genome, and disruption of
      geldanamycin production was observed as a result of homologous recombination
      between the cloned insert in recombinant phage and the S. hygroscopicus 17997
      genome by integration. Thiostrepton resistant transductants were selected and
      integration event was analyzed by Southern hybridization. The fermentation broth
      extracts from five resistant transductants were analyzed by TLC and HPLC. The
      results showed that only G16 mutant failed to produce geldanamycin. This result
      showed that the integration of the insert DNA fragment in recombinant phage phl6
      into the chromosome of S. hygroscopicus disrupted the expression of the
      geldanamycin biosynthetic genes. The original cosmid pCGBK10 containing this
      cloned insert was predicted to encode PKS genes in the geldanamycin biosynthesis.
      This study laid the foundation for cloning the PKS genes involved in geldanamycin
      biosynthetic gene cluster from S. hygroscopicus 17997.

PMID- 15969056
TI  - [Establishment of Spodoptera exigua multicapsid nucleopolyhedrovirus BAC-TO-BAC
      expression system].
AB  - Present studies describe the successful establishment of Spodoptera exigua
      multicapsid nucleopolyhedrovirus (SeMNPV) BAC-TO-BAC expression system. The mini
      F-lacZ-attTn7-kan fragment (Luckow et al, 1993) was inserted into SeMNPV US1
      isolate (SeUS1) at polyhedrin gene locus by directly cloning. The recombinant
      virus containing low-copy-number mini-F replication, which named bacmid, can
      propagate in Escherichia coli. Because SeUS1 isolate is make up of several
      genotypes and one bacmid carries one SeMNPV genotype, the SeUS1 BAC library is
      established by all SeMNPV bacmids (SeBAC). REN analysis for 111 SeBAC shows that
      SeUS1 consists of the genotype with whole SeMNPV genetic information and several
      genotypes with various different deletions. Progeny virus can be produced in
      insect cell line after transfection with SeBAC10, which carries the whole SeMNPV
      genome. So SeBAC10 is a shuttle vector that can replicate in eukaryocyte as well
      as prokaryocyte. Considering the insert mutation of SeMNPV polyhedrin gene (Seph)
      in SeBAC10, Seph was reintroduced into the bacmid by site-specific transposon
      mediated insertion at attTn7, the target site for the bacterial transposon Tn7.
      The derived recombinant SeBAC10 was named SeBAC10ph. After SeBAC10ph was
      transfected into Se301 cells (a susceptible insect cell line to SeMNPV),
      cytopathogenic effect was shown and polyhedra appeared, which indicate that the
      foreign gene (Seph) is expressed.

PMID- 15969057
TI  - [Optimization of T-dNA insertional mutagenesis and analysis of mutants of
      Magnaporthe grisea].
AB  - The rice blast fungus Magnaporthe grisea causes one of the most destructive
      diseases of rice around the world. Significant progresses have been made recently
      in genomics studies of the fungus, opening new era of the functional genomics
      which requires to generate a large scale of gene knockout mutants. It has been
      demonstrated that T-DNA insertional mutagenesis is a powerful tool of functional
      genomics not only for plants but also for fungi. In this paper, we optimized the
      conditions for T-DNA insertional mutagenesis of M. grisea using Agrobacterium
      tumefaciens-mediated transformation (ATMT) approach. We employed the binary
      vector pBHtl constructed by Dr. S. Kang's laboratory at the Pennsylvania State
      University, which carries the bacterial hygromycin B phosphotransferase gene
      (hph) under the control of the Aspergillus nidulans trpC promoter as a selectable
      marker to transform the conidia of M. grisea. We optimized the conditions for T
      DNA insertional mutagenesis including the medium, dosage of hygromycin B,
      cefotaxime and carbenicillin to select the transformants and inhibit the growth
      of A. tumefaciens after co-culturing. The dosage to inhibit non-transformants
      could vary from 200-600microg/mL among different M. grisea isolates so that the
      optimal dosage of the antibiotics should be decided according to isolates. Rice
      polished agar medium was found the best selection medium which would facilitate
      the mutant sporulation and minimize the contamination chance. In average, about
      500 transformants could be obtained when transforming 1 x 10(6) spores at the
      optimum condition, among which 85% had T-DNA insertion detected by polymerase
      chain reaction (PCR) and thermal asymmetric interlaced polymerase chain reaction
      (TAIL-PCR). Fifteen out of 1520 transformants showed mutation in colony
      morphology. Within 58 randomly selected mutants, it was found that there were 4
      sporulation-decreased mutants, 8 less germination mutants and 9 appressorium
      defective mutants. Several virulent mutants to C101LAC(Pi-1)and 75-1-127(Pi
      9)were also obtained which would facilitate cloning the corresponding avirulence
      genes.

PMID- 15969058
TI  - [Expression of phosphoprotein P2 of Cysticercus cellulosae in Pichia pastoris and
      its application].
AB  - Cysticercosis is caused by the metacestode form of Taenia solium-Cysticercus
      cellulosae and it causes great economic losses and threatens the people's health.
      There are some problems on how to control cysticercosis, in order to resolve the
      key problem that the native antigen to diagnose and prevent cysticercosis is very
      limited and is not satisfied, Pichia pastoris Expression System was used to
      express recombinant P2 protein. The interested P2 gene was got by digesting the
      pGEM - P2 vector using restriction endonuclease, then it was inserted into the
      secretory pPIC9K Pichia pastoris expression vector and transformed into E. coli.
      Positive recombinant plasmids were selected sequenced and named pPIC9K-P2 and it
      was linearized by Sal I and Bgl II, then the linear DNA transfored into Pichia
      pastoris GS115 by electroporation. The recombinant expression vector pPIC9K - P2
      integrated into GS115 via homologous recombination between the transforming DNA
      and regions of homology within the genome. The transformants were screened for
      multicopy recombinants using G418 and were distinguished for Mut phenotypes by MD
      and MM. Two different phenotypes were generated-HIS+ MUT+ (Methanol utilization
      plus) and HIS+ MUT(S) (Methanol utilization slow). PCR analysis of the multicopy
      recombinants indicated that the P2 gene was integrated within the genome of
      pichia Pastoris. The multicopy recombinants were named GS115/pPIC9K - P2HIS+ MUT+
      and GS115/pPIC9K-P2HIS+ MUT(S), both HIS+ MUT+ and HIS+ MUT(S) were induced with
      methanol. The results of SDS-PAGE and Western blot demonstrated that the culture
      supernatant of the induced Pichia pastoris contained P2 protein which was
      accumulated up to 33 % of total proteins in the culture supernant and its
      molecular weight is 12.6kD. The results of the clinical study indicated that the
      expression P2 protein could be used to diagnose human cysticercosis and swine
      cysticercosis as diagnosis antigen.

PMID- 15969059
TI  - [The effects of the Smad3-knockout on the hematopoiesis of mouse].
AB  - The effects of the Smad3- knockout on the hematopoiesis of mouse were
      investigated in this work. Five pairs of wild type and Smad3- null mice were
      studied. White blood cell(WBC), red blood cell(RBC) and platelet (PLT) counting
      of peripheral blood cells were performed with blood obtained from tails. And
      white blood cells were classified by their morphology. Bone marrow nucleated
      cells (BMNCs) were counted and classified. The CFU-GM, BFU-E, CFU-GEMM yields
      were measured in each pair of mice. CFU-S yield of each mouse was measured by
      injecting bone marrow cells into lethally irradiated 8-10 weeks old wild type
      female mice. And the pathomorphism of their bone marrows, spleens and livers were
      observed. As a result, WBC and PLT of Smad3- null mice were significantly higher
      than those in wild type mice. Smad3- null mice had much more proportion of
      granulocytes in classification. There wasn't any difference in RBC counting and
      BFU-E measurement. The yield of CFU-GM increased, while the yields of CFU-GEMM
      and CFU-S markedly reduced. Bone marrows are actively proliferative, with
      granulocytosis. The granulocyte/erythrocyte ratio increased. There were no
      obviously alterative in spleen and liver. Thus Smad3- knockout results in a
      decreased number of stem and progenitor cells. Moreover hematopoietic
      differentiation is abnormal with a tendency to forming more granulocytes and
      platelets. The effect of Smad3 on hematopoiesis is correlative to that of TGF
      beta.

PMID- 15969060
TI  - [Construction of the attenuated Salmonella typhimurium strain expressing
      Helicobacter pylori conservative region of adhesin antigen].
AB  - To construct a non-resistance and attenuated Salmonella typhimurium strain which
      expresses conservative region of adhesin(AB) of Helicobacter pylori(Hp). The AB
      gene was amplified by PCR and inserted into the expression vector pYA248
      containing asd gene and was introduceded into the delta Cya, delta Crp, delta Asd
      attenuated Salmonella typhimurium strain by twice transformations, which is a
      balanced lethal recombinant. Bridged ELISA method was used to measure AB
      expressed in sonicate and culture supernatant. According to Meacock's way and
      growth curve, stability of the recombinant is evaluated. Semi-lethal capacity
      test was used to evaluate the safty of recombinant. Results showed S. typhimurium
      X4072(pYA248-AB) was constructed successfully, recombinant X4072(pYA248- AB)
      content of supernatant serum was higher than that of thallus lytic liquor
      confirmed by bridged ELISA, and after recombinant pYA248- AB cultured 100
      generation without selection pressure, all the recombinant germ selected randomly
      can grow, and the AB antigen was positive by ELISA detection. The growth curve of
      the recombinant germ showed that the growth state of X4072(pYA248) and
      X4072(pYA248- AB) were coincidence on the whole, and the survival rate of C57BL/6
      was still 100%, 30 days after taking X4072(pYA248- AB) 1.0 x 10(10)cfu. orally.
      Non-resistance S. typhimurium X4072(pYA248- AB) was constructed successfully. The
      recombinant plasmid was stable indicated by in vitro experiment. And the
      recombinant strain was safe confirmed by animal experiment. This live vaccine
      strain is worthy to be considered as a new live oral vaccine candidate against Hp
      infection.

PMID- 15969061
TI  - [Site-directed mutagensis of the major antigen E2 gene of CSFV, its high level
      expression in Escherichia coli and the immunonicity of recombinant E2 protein].
AB  - Classical swine fever virus (CSFV), an enveloped positive-stranded RNA virus in
      the genus Pestivirus of the Flaviviridae family, is the causative agent of a
      highly contagious swine disease characterized by symptoms of hemorrhagic fever
      and immune depression, usually leading to substantial economic losses. The
      serological methods for detection of CSFV antibody such as ELISA are important
      means for the diagnosis of CSFV and immune surveillance. It is difficult to
      obtain CSFV antigen with high quality using traditional method because its
      titration titer is low in cell culture. CSFV has four structural protein named C,
      E0, El and E2. The E2 protein contains major antigenic determinants that are
      conserved between different CSFV strains and involved in neutralization by
      antibodies. So recombinant E2 protein can be developed as an alternative to the
      intact viral antigen. So far, CSFV E2 have not been expressed in E. coli with
      high level. Many factors, such as the secondary structure, the stability of 5'
      and 3' terminus of gene, the location of SD sequence and the bias of codes, are
      involved in the expressing level of foreign gene in E. coli . In this study, two
      sites of the E2 gene sequence were confirmed to be detrimental to its expression
      efficiency in E. coli through the computer-aided analysis. So they were mutated
      using recombinant PCR without changing the amino acids sequence of CSFV E2 gene.
      A plasmid was constructed by inserting the mutated E2 gene into the prokaryotic
      expression vector pET-28a(+) and named pETE2. The E. coli competent host BL21
      (DE3)lysS transformed with pETE2 could express the E2 gene at high level,
      amounting to 28% of the total protein of the induced recombinant bacteria at the
      presence of IPTG. Except the hydrophobic transmembrane domain at C terminus, the
      recombinant E2 protein includes the total aa sequence. So it contains all the
      potential linear antigen epitopes of E2 protein because hydrophobic aa region can
      not form epitope. The recombinant E2 protein was CSFV-specific as proved by
      Western blotting and indirect ELISA. The rabbits immunized with the recombinant
      E2 can be protect from the challenge of hog cholera lapinized virus. This is the
      first report that E2 gene is expressed with high level expression in E. coli. In
      conclusion, it is an effective measure that mutate the CSFV E2 gene to increase
      its expression level in E. coli. The recombinant CSFV E2 protein possess fine
      immunonicity and can be used the antigen for the detection of CSFV antibody.

PMID- 15969062
TI  - [Construction and expression of anti-CD3/ anti-Pgp Diabody].
AB  - The use of tumor antigen specific antibodies for the delivery of therapeutic
      agents offers the possibility of targeting therapy with reduced toxicity to
      normal tissues compared to conventional treatments. However, several factors
      restrict the use of anti-PGP monoclonal antibodies(Mabs). First, Pgp is expressed
      in normal tissues, particularly in epithelial and endothelial cells of the
      gastrointestinal tract, liver, kidney, blood brain barrier, choroids plexus and
      other organs. It plays a significant role to transport drugs and toxins in these
      organs. Therefore, anti-PGP antibodies in combination with cytotoxic compounds or
      radiolabelled antibodies should neither inhibit the activity of PGP, nor harm the
      cells which expressed PGP normally. BiMab exploit the specificity of Mab and
      ensures activation of cellular cytotoxic mechanisms which kill tumor cells only,
      but not harm normal cells. It will provide a strategy for resistant cancer
      therapy using anti-PGP antibodies. Second, Repeated administration of murine
      antibodies generates a strong human anti-mouse immune (HAMA) response in up to
      50% of patients after the first dose, and appro ximately 90% following a second
      treatment. In an effort to reduce the toxicity and antigenicity, we focus to
      produce anti-PGP antibodies which have the binding activity only, but not inhibit
      the function of the "pump", and to construct a small and partially humanized
      recombinant molecule with dual specificity for both PGP and CD3 complex to
      activate the host immune response toward the tumour. PCR and overlap PCR were
      used to construct anti-CD3/ anti-Pgp Diabody. DNA sequence was analyzed by the
      Terminus of Dideoxy Nucleotide. The product was purified by affinity
      chromatography and analyzed by both the detection of western blot and size
      exclusion chromatography; its antigen-binding activity was examined by FACS,
      cellular RIA. Plasmid pAYZDCP which expressed the anti-CD3/anti-Pgp Diabody was
      constructed correctly. The diabody was recovered in high yield( up to 2mg/ L)
      after E-taq purification and predominantly(90%) as a dimer. The diabody can bind
      to Jurkat cells (CD3+) and K562/A02 cells(Pgp+). The affinities of the diabody
      were similar with the anti-CD3 ScFv or anti-Pgp ScFv, respectively. The anti-CD3/
      anti-Pgp BsF(ab')2 was first recast into the diabody format and succeeded to
      obtain high level expression. The results of some biological activity experiments
      indicated that the diabody could bind to Jurkat cells and K562/A02 cells.
      Multidrug resistance can be reversed experimentally by a variety of drugs, among
      which the best known are verapamil and trifluoperazine, which unfortunately are
      of limited use in practice due to severe collateral cardiac toxicity. Anti-PGP x
      anti-CD3 diabody will provide another therapeutic strategy against multidrug
      resistance cancer.

PMID- 15969063
TI  - [Expansion of bone marrow LTC-ICs in vitro by mouse fetal liver-derived stromal
      cell lines].
AB  - As main component of fetal liver hematopoietic microenvironment, different
      stromal cells may play distinct roles in the regulation of hematopoietic stem
      cell self-renewal, proliferation and differentiation. It is a unique approach to
      establish stromal cell lines for analyzing the interaction of hematopoietic cells
      with the stroma on the clonal level to dissect the function of hematopoietic
      microenvironment. In this study two immortal stromal cell lines-A4, B3 were
      established from mouse embryonic day 12.5 fetal liver by transfection of pSV3 neo
      plasmid. A4 exhibited a fibroblast-like morphology, 25 hours population doubling
      time as well as high levels of CD29, CD44, UEA-1 and low levels of CD105
      expression. In contrast B3 displayed an epithelium-like morphology, 37 hours
      population doubling time along with high levels of CD105 and low levels of UEA-1
      expression. In addition no or low levels of CD31, CD34, CD45 and CD144 expression
      were found in the two cell lines. These results indicate that A4, B3 are two
      discriminating cell lines in terms of morphological characters, growth behaviors
      and surface molecular expression types. Next functional assays using Limited
      Diluted Assay(LDA) and Bulk-LTC-IC were done: both stromal cell lines had similar
      ability to maintain the survival proportion of inoculated mouse bone marrow
      derived Long-Term Culture-Initiating Cells (LTC-ICs), and they could also support
      LTC-ICs expansion up to 4 weeks by co-culture in vitro. More strikingly, B3 could
      expand the absolute number of LTC-ICs over 13-fold at week 4 than that of week 0,
      and the ability of B3 to expand absolute number of LTC-ICs was over 8-fold of
      that of A4. Proportions of LTC-ICs in proliferating cell populations in two long
      term culture systems was similar at week 4, no matter with or without extra
      cytokines. Further study indicated that the ability of LTC-ICs to yield CFCs was
      held as the number 6( +/- 1.2) after 4 weeks co-culture. Extra cytokines-SCF + IL
      3 + IL-6 + Epo had no influence in the maintenance and expansion of LTC-ICs, but
      expanded the absolute number of CFCs and proliferating cell populations, and
      maintained similar proportions of LTC-ICs and CFCs in the end in two culture
      systems at week 4. Take together, these results implicate that B3 may act as an
      important functional component in embryonic day 12.5 fetal liver microenvironment
      to effectively expand primitive hematopoietic cells, yield more committed
      hematopoietic progenitor cells and mature hematopoietic cells to meet the need of
      quick development especially in the early phase of embryonic development.
      Alternatively A4 can probably function as being a structural element. Moreover
      the function of hematopoiesis-associated cytokines employed in this investigation
      was not to expand LTC-ICs, but to modulate the limited-proliferation and
      differentiation of CFCs. The maintenance and proliferation of LTC-ICs may depend
      on the type of the stromal cell as well as the interaction between stromal cells
      and LTC-ICs. It is suggested that B3 with cytokines including SCF, IL-3, IL-6,
      EPO in vitro can mimic embryonic day 12.5 hematopoietic microenvironment to
      investigate the mechanism of interaction between hematopoietic microenvironment
      and hematopoietic cells in clonal level.

PMID- 15969064
TI  - [Recovery of platinum with immobilized Citrobacter freudii XP05 biomass].
AB  - The objective of this work was to develop a valuable adsorbent for recovery of
      platinum by studying the properties of Pt4+ -adsorption with immobilized
      Citrobacter freudii XP05 biomass. Five methods for immobilization of Citrobacter
      freudii XP05 biomass were compared. The method with gelatin-alginate sodium as
      entrapment matrix was considered to be the optimal. Spherical and uniform beads
      were produced and the SEM micrograph indicated that the cell of strain XP08 were
      uniformly dispersed within the matrix. The adsorption of Pt4+ by immobilized XP05
      biomass was affected with adsorptive time, pH value of the solution, immobilized
      biomass concentration, Pt4+ initial concentration The adsorption was a rapid
      process. The optimal pH value for Pt4+ adsorption was 1.5, and its adsorptive
      capacity increased linearly with increasing Pt4+ initial concentrations in the
      range of 50 - 250 mg/L. The experimental data could be fitted to Langmuir and
      Freundlich models of adsorption isotherm. The adsorptive capacity reached 35.2
      mg/g under the conditions of 250 Pt4+ mg/L, 2.0 g/L immobilized biomass, pH 1.5
      and 30 degrees C for 60 min. 98.7% of Pt4+ adsorbed on immobilized biomass could
      be desorbed with 0.5 mol HC1/L. The characteristics of dynamic adsorption and
      desorption of immobilized XP05 biomass in packed-bed reactor were investigated.
      The saturation uptake was 24.66 mg Pt4+ /g under the conditions of flow rate 1.2
      mL/min, pH 1.5, 50 mg Pt4+/L and 1.85 g biomass(dry weight) . Adsorptive
      efficiency of Pt4 + by the immobilized XP05 biomass was above 78% for 4 cycles of
      adsorption and desorption. The recovery of platinum from waste platinum catalyst
      was studied. The adsorptive capacity was 20.94 mg Pt4+/g immobilized biomass
      under the conditions of 4.0 g/L immobilized XP05 biomass, 117.76 mg Pt4+/L and pH
      1.5 for 60 min. The immobilized XP05 biomass is potentially applicable to the
      recovery of platinum from waste and wastewater containing platinum.

PMID- 15969065
TI  - [Establishment and biological properties of hybridoma cell lines secreting anti
      IBDV idiotypic antibodies].
AB  - In recent years, the prevention and cure of infectious bursal disease (IBD) have
      become more and more difficult due to the emergence of very virulent strains of
      infectious bursal disease virus (vvIBDV) and the variant strains of IBDV. In this
      research, the hybridoma cell lines which secretes anti-idiotypic antibodies
      against anti-IBDV IgG were established. According to the Jerne's theory of immune
      network, the use of the anti-idiotypic antibodies as a vaccine will be a new
      method for the prevention of IBD. In this study, the SPF chickens were inoculated
      with the IBDV- SD strain, and the bursal was obtained from the died chickens. The
      bursal was then homogenized and frozen-thawed 3 cycles, and the virus samples
      were prepared by cane sugar density gradient centrifugation and dialysis. Typical
      IBDV particles were observed under an electron microscope, and the concentration
      of the virus protein measured by ultraviolet absorbance spectrophotometry was
      10.8 mg/mL. SPF chickens were immunized with the virus and the highly immunized
      sera were prepared and purified by Sulfuric acid ammonia salt out and Sephadex G
      25 chromatography. Then, Balb/C mice of six or eight weeks old were immunized
      interapertoneally(I. P.) with purified antibodies to IBDV at regular intervals.
      SP2/0 myeloma cells were fused with the spleencytes from the immunized mice at a
      ratio of 10:1, in 50% polyethylene glycol (1540) and were then cultured in HAT
      until all the SP2/0 cells died. The hybridoma cells were selected by ELISA and
      the highly positive holes were cloned 3 times with the method of limited
      dilution. Two strains (2B6 strain,5F4 strain) of hybridoma cells were obtained,
      which were shown by ELISA to steadily secrete anti-IBDV idiotypic antibodies. The
      chromosome number of the two hybridoma cells were about 88 - 106, 95 in average,
      and the antibodies secreted belonged to the types of IgG1 and Kappa. Balb/c mice
      of 3 months old were inoculated I.P. with about 10(7) hybridoma cells per capita,
      and the ascites were collected 12 days later and the titre of anti-IBDV idiotypic
      antibodies measured by ELISA was 1 :25600 (for 2B6) and 1:12800 (for 5F4) . The
      ascites containing the anti-IBDV idiotypic antibodies were emulsified with
      complete or incomplete Freund's adjuvants, and the anti-IBDV idiotypic antibody
      vaccine was obtained. SPF and common Jingbai chickens were immunized with the
      vaccine obtained. The immunized chickens with the vaccine were inoculated with
      IBDV-SD strain at a dose of 2000 ELD50 after twoimmunizations. All the 10 SPF
      chickens in the non-immunized group were sick, and 8 of them died; and 5 out of
      the 50 SPF chickens immunized group got sick and 2 died. All the 10 common
      Jingbai chickens in the control group were sick, and 6 died; 7 of the 30
      immunized common Jingbai chickens got sick and only 1 died. Chi2 analysis showed
      that the difference between the immunized and the non-immunized groups in both
      the SPF and the common Jingbai chickens were significant (P < 0.01). Our result
      indicated that the anti-IBDV idiotypic antibody vaccine well protected chickens
      and had a great potential in both research and clinical application.

PMID- 15969066
TI  - [Feeding of mixed-carbon-resource during the expression phase in cultivation of
      recombinant Pichia pastoris expressing angiostatin].
AB  - A recombinant strain of Pichia pastoris with a phenotype of Muts was used to
      produce angiostatin in a 5-L fermentor. The methanol utilization ability of the
      present strain was weak, which resulted in extremely low growth rate and
      angiostatin productivity during the expression phase with methanol as the sole
      carbon source. To enhance the cell density and angiostatin expression level,
      mixed-carbon-source of glycerol-methanol was used in the expression phase. The
      methanol concentration was well controlled at 5 g/L by a methanol sensor and
      control system, and glycerol was continuously fed into the fermentor to achieve a
      higher cell density. 120 g/L of cells and 39 mg/L of angiostatin were reached at
      the end of fermentation which lasted 110 h. The mean specific cell growth rate in
      the expression phase was 0.01 h(-1), and the mean specific angiostatin
      productivity was 0.006 mg/(g x h). According to the data obtained in several runs
      of fermentation in which glycerol was fed at different rates, a higher mean
      specific angiostatin productivity was reached at the mean specific cell growth
      rate of 0.012 h(-1). To avoid the repression of angiostatin expression caused by
      residual glycerol and ethanol accumulation due to overfeeding of glycerol,
      glycerol addition was controlled to produce continuous oscillations in dissolved
      oxygen, because the change of dissolved oxygen concentration could deliver the
      information of available carbon source in the fermentation broth. Controlled
      glycerol feeding also avoided the problem of oxygen limitation brought by high
      cell density, and thus decreased the cooling requirement of the fermentor. Cell
      density reached 150 g/L at the end of fermentation, and angiostatin level reached
      108 mg/L after an expression period of 96 h when the mean specific growth rate
      was maintained at 0.012 h(-1) by using the glycerol feeding strategy to result in
      the oscillations in dissolved oxygen. The mean specific angiostatin productivity
      was improved to 0.02 mg/(g x h). The apparent cell yield on glycerol and methanol
      were respectively 0.69 g/g and 0.93 g/g, higher than those in the fermentation
      without using the feeding strategy with dissolved oxygen as the indicator of
      metabolism.

PMID- 15969067
TI  - [Application of element and metabolism balancing for the cultivation process with
      Streptomyces aureofaciens].
AB  - On the base of element and metablism balancing, the mathematical model of the
      cultivation process with Streptomyces aureofaciens was developed, and the unknown
      parameters in the model were estimated with the method of nonlinear optimization.
      Firstly the energetic coefficient of CTC biosynthesis was gained, which was 1.8 -
      2.8 mol-ATP x C-mol(-1). The macroscopic reaction rates were predicted in the
      process and compared with the experimental values. The results show that the
      model can preferably describe the relationships between several macroscopic
      reaction rates in the process and can supervise the optimization of CTC
      fermentation process theoretically.

PMID- 15969068
TI  - [CDNA cloning of human leptin and its expression].
AB  - To clone cDNA of human leptin gene and obtain leptin protein for future study on
      leptin binding proteins. The cDNA of human leptin with 6 x his-tag was cloned by
      over-hang extension PCR protocol using human genomic DNA as template, and
      subcloned into in vitro expression vector pIVEX2.3MCS, and the fusion protein was
      expressed in vitro by Rapid Translation System (RTS) (RTS500 cycle primer Kit and
      RTS500 ProteoMaster of Roche company). The apparent molecular weight(19.46 kD)
      and the immuno-specificity of the fusion protein were confirmed by SDS-PAGE and
      Western blot, and the expressed fusion protein stayed mainly in the supernatant
      of the reaction mixture in soluble form. This work provides us solid basis for
      further study on new leptin-associated proteins.

PMID- 15969069
TI  - [Molecular cloning, expression mutation of myostatin and study on biochemical
      activity of its C-terminal peptide].
AB  - Myostatin, a member of the TGF-beta family, negatively regulates skeletal muscle
      development. Mutation of myostatin activity leads to increases muscle growth and
      carcass lean yield. The bovine myostatin mutation cDNA was amplified by
      polymerase chain reaction, and then sub-cloned into the expression vector pET
      30a( + ) to form the expression plasmid pET30a (+)-action/ Myostatin. The
      recombinant plasmid was transformed into E. coli BL21. The overexpression product
      of pET30a (+)-action/ Myostatin was been showed in vitro. Sheep skeletal muscle
      cell were cultured with the purified myostatin mutation C-terminal peptide. The
      results of this study suggest that had a powerful activity to stimulate the
      hyperplasia and proliferation of sheep muscle cells and shows high biochemical
      activity.

PMID- 15969070
TI  - [Collagen membrane as scaffold for the three-dimensional cultivation of cardiac
      cells in vitro].
AB  - The objective of this study was to develop research of cardiac cells to
      reestablish 3D tissue architecture in vitro, we performed studies using collagen
      membrane as three-dimensional scaffold for cardiac cells culture with the
      principles and methods of tissue engineering. The polymer scaffold provides a 3-D
      substrate for cell attachment and tissue formation. Cardiac cells isolated by
      enzymatic digestion from 1d old neonatal rats were seeded to three-dimensional
      collagen scaffolds and tissue culture plates. The morphology, beating rate and
      the metabolic indexes, including specific consumption rate of glucose (q(glu)) ,
      specific production rate of lactate (q(lac)), lactate transform rate (
      Y(lac/glu)), specific creatine kinase (CK) and lactate dehydrogenase (LDH)
      activities of cardiac cells cultured on three-dimensional collagen membrane and
      tissue culture plates were compared. It was found that cells shape and cells' CK
      and LDH activity was no differences between 3D and 2D cultures and cell beat rate
      on cell culture cluster was slower than those cells cultured on collagen
      membrane, However the cell glucose consumption and lactate yield rate of cells
      cultured on cluster was higher than those cells cultured on collagen membrane.
      After 5 days of cultivation, cardiac cells cultured on collagen membrane
      scaffolds organized into three-dimensional (3D) aggregates as opposed to the two
      dimensional (2D) aggregates mosaic pattern seen in tissue culture plates, and
      spontaneous and rhythmical contractile 3D cultures in unison were visible to the
      naked eye and the area of synchronous contract three-dimensional (3D) aggregates
      reaches 80cm2. The mean value of q(glu), q(lac) and Y(lac/glu) of cultured on
      three-dimensional collagen scaffold was 7.37 micromol/10(6) cells/d, 2.92
      micromol/10(6) cells/ d and 0.38 micromol/micromol, versus 7.59
      micromol/10(6)cells/d, 3.83 micromol/10(6) cells/d and 0.51 micromol/micromol in
      tissue culture plates. These results demonstrate that cardiac cells immobilized
      on collagen membrane in 3D cultures maintain similar metabolic activity and
      contractile function when compared with native cardiac cells. The above results
      support the idea that engineered cardiac tissue can be used as a model of native
      tissue for studies of tissue development and function in vitro and eventually for
      tissue repair in vivo.

PMID- 15969071
TI  - [Effects of different cooling rates on cryopreservation of hematopoietic stem
      cells from cord blood].
AB  - Clinical evidence of hematopoietic restoration with umbilical cord blood (UCB)
      grafts indicates the UCB can be a useful source of hematopoietic stem cells for
      routine bone marrow reconstitution. Considering (10 +/- 5) x 10(8) nucleared
      cells per cord blood unit, there is a potential limitation for the use of cord
      blood in adults, which, however, can be overcome by ex vivo expansion of cells. A
      prerequisite for expansion is the significantly higher recovery of MNC, CD34+
      cells and colony-forming cells (CFC) by thawing cryopreserved MNC. Cooling rate
      always acts as a critical factor that can affect the recovery of cells. Although
      the rate of - 1 degrees C/min is adopted in most of the cryopreservations, no
      data has been reported about the detailed effects of different cooling rates. The
      aim of the study was to reveal the different effects of cooling rates on
      cryopreservation of hematopoietic stem cells from cord blood. UCB samples were
      collected, and cryopreserved as mononuclear cells (MNC) with different cooling
      rates of - 0.5 degrees C/min, - 1 degrees C/min, - 5 degrees C/min, and the
      recovery and viability of MNC and CD34+ cells, the clonogenic capacity and the ex
      vivo expansion potential of UCB progenitor cells were evaluated after thawing.
      With - 1 degrees C/min cooling rate, the recovery of MNC reached 93.3% +/- 1.8% ,
      viability 95.0% +/- 3.9% , recovery of CD34+ cells 80.0% +/- 17.9% , and
      clonogenic recovery were 87.1% +/- 5.5%, 88.5% +/- 8.9%, 86.2% +/- 7.4% for BFU-E
      CFU-GM CFU-MK, respectively. After 14 days of liquid culture, no significant
      difference was detected in CFC expansion between fresh and cryopreserved MNC
      cells with - 1 degrees C/min cooling rate, but this was not the case with - 0.5
      degreesC/min and - 5 degrees C/min. In conclusion, it was demonstrated that
      controlling the rate at - 1 degrees C/min is more suitable for cryopreservation
      of hematopoietic stem cells than - 0.5 degrees C/min and - 5 degrees C/min.

PMID- 15969072
TI  - [Studies on the mechanism of thermostability and thermophilicity change of
      thermostable alkaline phosphatase and its mutants].
AB  - The relationship among the substituted amino acids, the 3D structure simulated on
      PC through CPHmodels Server ( http://www.cbs.dtu. dk/services/CPHmodels/) and the
      thermostable performance of 4 thermostable alkaline phosphatase(TAP) mutants
      selected from a clone bank of more than 200 mutants were analyzed to explore the
      mechanism of thermostability change. These mutants are TAP(A410T) (A410-->T),
      TAP(P396S) (P396-->S), TAP2(N100S T320-->I) and TAP4(N100-->S P396-->S A410 -->V
      P490-->S). TAP and the mutants' thermostable performance was evaluated by
      measuring the highest tolerable temperature (T1/2) and the optimal reaction
      temperature (Topt). The 3D structure neighboring the substituted amino acids was
      simulated by Swiss-PDBViewer to observe the relationship between the structure
      change and the thermostable performance of TAP and its mutants. The results
      displayed that all these amino acid substitutions except the T320-->I mutant
      brought about only a little local change on TAP's 3D structure and very little
      effect on their optimal reaction temperature, but a significant decrease (nearly
      10 degrees C) on their highest tolerable temperature. However, the T320-->I
      mutation due to close to TAP's active sites did bring about a significant
      descendents of the mutant in both the highest tolerable temperature and the
      optimal reaction temperature. Thus, it seems to be able to conclude that most of
      the amino acid substitutions, no matter where they locate and what structure
      change they may make, can cause TAP's highest tolerable temperature reduced
      significantly. What's more, if the mutation occurring near or in the active
      sites, it can also cause TAP's optimal reaction temperature reduced significantly
      at the same time.

PMID- 15969073
TI  - [Formation of polyhydroxyalkanoates during the dual-nutrient-limited zone by
      Ralstonia eutropha].
AB  - Polyhydroxyalkanoates (PHAs) are a class of polyesters biosynthesized by
      microorganisms (esp. Ralstonia eutropha) under an unbalanced growth condition,
      and which are supposed to partly take the place of traditional plastics made from
      petroleum in the near future since they are harmless to the environment and
      biodegradable. Organic acids (mainly butyrate, lactate, propionate and acetate)
      produced from anaerobic digested food wastes, industrial wastes and sewage may be
      used as cheap carbon sources since the large amounts of the above wastes disposed
      by industry and family each year. In order to better understand the process of
      PHAs formation with acids as carbon sources, so as to increase the yields of
      PHAs. Biosynthesis of PHAs by R. eutropha during the dual nutrient-limitation
      zone was investigated with mixed organic acids (the mass ratio of the four
      component acids was butyrate: propionate: acetate: lactate = 3: 3: 1: 1, which
      was simulated as once the result of anaerobic digestion of food wastes) as carbon
      sources and (NH4)2 SO4 as nitrogen source. Two different manners of maintaining
      the dual-nutrient-limitation zone were adopted by feeding mixed acids and (NH4
      )2SO4 at determined rates to the fermentation culture which were free of carbon
      sources (manner A) or nitrogen sources (manner B) firstly. The results suggest
      that, first of all, the meaning of the limitation of mixed acids or (NH4)2 SO4
      does not mean to limit the supply of them, but mean to feed as more as possible
      of carbon and nitrogen sources in order to meet the cell growth and PHAs
      formation of R. eutropha by the largest extent. However, it's indispensable to
      make the residual concentration of carbon and nitrogen sources as low as possible
      since organic acids are inhibitive to the cell growth, and most importantly, only
      under the presence of nitrogen during the PHAS formation period of the
      fermentation could R. eutropha produce more PHAs than any other unbalanced growth
      condition. Secondly, with the increase of the width of the dual-nutrient
      limitation zone, the yield of PHAs would also increase, it suggest that most of
      the PHAs were biosynthesized during the dual-nutrient-limitation zone. Finally,
      in contrast with the dual-nutrient-limitation manner of limiting the nitrogen
      source at first (manner B), the dual-nutrient-limitation manner of limiting the
      carbon source at first (manner A) was more favorable for the production of PHAs,
      and the maximum production of PHAs of these two manners are 3.72 g/L and 2.55
      g/L, respectively. It may be because that PHAs formation required enzymes could
      not be well developed when R. eutropha grow under the state of nitrogen
      limitation from the beginning of fermentation. Besides, yield of PHAs produced by
      the dual-nutrient-limitation fermentation is larger than that of the single
      nutrient-limitation batch culture. Therefore, it seems that to increase the
      output of PHAs production, the strategy of maintaining as wide as possible the
      width of dual-nutrient (C, N)-limitation zone may be effective.

PMID- 15969074
TI  - [Co-culture of embryos: influencing factors and mechanisms of action].
AB  - In comparison with their in vivo counterparts, the in vitro produced mammalian
      embryos had markedly lower rates of morula/blastocyst development and pregnancy
      after transfer to the recipients. Things became even worse in the cloned embryos.
      This necessitates improvement of the embryo culture system. Co-culture of embryos
      with different types of somatic cells was found beneficial for embryo development
      in vitro and many studies have been conducted in this area in recent years. In
      this paper, recent developments and the authors' own work in studies of co
      culture of early mammalian embryos with somatic cells were reviewed, with
      emphasis on the effects of cell type, stage of estrous cycle and number of
      passages of somatic cells and supplement of serum on embryo development, and the
      mechanisms by which co-culture promote embryo development. The recent
      developments are summarized as follows: 1. Somatic cells of both homogeneous and
      heterogeneous origins can be used for co-culture of mammalian embryos, with
      similar developmental rates. 2. Supplementation of animal serum at appropriate
      concentrations improved the somatic cell growth and consequently the development
      of embryos in co-culture. 3. The estrous cycle stages of oviduct epithelial cells
      used for co-culture had no effect on the development of embryos. 4. Over
      passaging of somatic cells reduced their efficiency in promoting development of
      the co-cultured embryos. In conclusion, studies have shown that co-culture
      overcame the block of embryo development in vitro and improved embryo quality
      with increased rates of implantation and pregnancy, but many problems remain to
      be solved on its influencing factors and mechanisms of action.

PMID- 15969075
TI  - [The PKS/NRPS hetero-gene cluster of epothilones].
AB  - Novel macrolides epothilones, produced by cellulolytic myxobacterium Sorangium
      cellulosum, have the activity to promote microtubule assembly, and are considered
      to be a potential successor to the famous antitumor drug taxol. The biosynthetic
      genes leading to the epothilones are clustered into a large operon. The multi
      enzyme complex is a hetero-gene cluster of polyketide synthase (PKS) and non
      ribosomal peptide synthetases (NRPS) and contains several functional modules,
      i.e. a loading module, one NRPS module, eight PKS modules, and a P450 epoxidase.
      The former ten modules biosynthesize desoxyepothilone (epothilones C and D),
      which is then epoxidized at C12 and C13 and converted into epothilones
      (epothilones A and B) by the P450 epoxidase. The NRPS module is responsible for
      the formation of the thiazole side chain from cysteine. The biosynthesis
      procedure of epothilones can be divided into 5 stages, i.e. formation of holo
      ACP/PCP, chain initiation and thiazole ring formation, chain elongation,
      termination and epoxidation, and post-modification. The analysis of the gene
      cluster and the biosynthetic pathway reveals that novel epothilone analogs could
      not only be produced by chemical synthesis/modification, tranditional microbial
      technologies, but also can be genetically manipulated through combinatiorial
      biosynthesis approaches.

PMID- 15969076
TI  - [The structure and virus-like particle vaccine of the HIV-1 capsid protein].
AB  - The HIV-1 capsid protein (CA) plays an essential role in viral core assembly and
      maturation. Proteolytic cleavage at the MA-CA junction of the retroviral gag
      polyprotein refolds the amino-terminal end of capsid into a beta-helix structure
      that is stabilized by a salt bridge between the protein's processed amino
      terminus and a conserved acidic residue. The refolded capsid aminoterminus then
      creates a new CA-CA interface, allowing assembly of the mature capsid core.
      Recently, researches focus on assembly of CA in vitro and development of CA
      vaccine. CA vaccine will provide widely immune protection because CA is
      comparatively conserved. Experiments demonstrate that fusing as few as four
      matrix residues onto the amino-terminus of capsid redirects protein assembly from
      cylinder to spheres in vitro. Evaluation of immunogenicity showed that
      immunization with virus-like particles induced both cellular and neutralizing
      antibody responses. Furthermore, mucosal administration of virus-like particles
      effectively induced both mucosal and systemic immune responses. These results
      indicate that virus-like particles consisting of HIV structural proteins are an
      attractive vaccine platform for eliciting anti-viral immune responses, especially
      neutralizing antibody responses. The production of antigens for vaccines in
      plants indicates that plant-based transgenic expression represents a viable means
      of producing CA vaccine for the development of HIV vaccine and for use in HIV
      diagnostic procedures and it has the potential as a safe and cost-effective
      alternative to traditional production systems.

PMID- 15969077
TI  - [Expression plasmid-host strain using chromosome-plasmid balanced lethal system
      based on the Escherichia coli thyA].
AB  - To construct a vector for DNA vaccine and protein expression by using chromosome
      plasmid balanced lethal system which was based on the thyA+ gene/deltathyA
      Escherichia coli. The thyA genes from Escherichia coli and Vibrio cholerae were
      amplified by polymerase chain reaction and cloned into pCDNA3 by replacing
      ampilicilin resistant gene. Multiple cloning sites, the prokaryotic replicon, CMV
      promoter and the boving growth hormone polyA signal were also included in the
      vectors. Two new non-antibiotic recombinant plasmids renamed as pcDNATE and
      pcDNATC which had the nutritional marker as thyA were constructed and were
      transformed respectively into the deltathyA derivative of E. coli K-12 strain
      DY330-TI, then two chromosome-plasmid balanced systems for E. coli based on the
      thyA were developed. To test the efficiency and stability of the newly
      constructed chromosome-plasmid balanced lethal system, a reporter gene--red
      fluorescent protein (DsRed2) gene was cloned into pcDNATE, pcDNATC and expressed
      as fusion to the c-myc. The two recombinant plasmids, pcDNATE-DsRed2, pcDNATC
      DsRed2, were transfected into HEK293 solely and DsRed2-myc was detected by the
      fluorescence microscope assay and western-blot. Meanwhile, the loss of
      recombinant plasmids were not seen in cultures without thymidine after 20
      generations. The chromosomal-plasmid balanced lethal system is proved to be an
      effective vector system for the expression of target genes and share the same
      stability with the antibiotic-resistant plasmid vector system. It holds great
      potential in gene vaccine vector because obviating the weakpoints of the drug
      resistance marker during application.

PMID- 15969078
TI  - [Expression of chimeric anti-CD3 IgG antibody in mammalian cells and analysis of
      its biological activity].
AB  - The anti-CD3 antibody can improve success rate of organs transplant. HIT3a, a
      mouse anti-CD3 antibody, was chimerized by using gene engineering methods to
      decrease its immunogenity. The anti-CD3 genes, heavy chain and light chain, were
      cloned using PCR from the vector pCANTAB 5E containing anti-CD3 scFv gene
      fragment, and two PCR fragments were recombined into the expression vector pKN100
      with human antibody light constant domain and pG1D105 with human antibody heavy
      constant domain, respectively. The two vectors were co-transfected into CHO cells
      using liposome. The anti-CD3 antibody was detected by ELISA and Western blot
      assay in supernatant of transfected CHO cells culture. The primary results of
      competitive assays by FACS showed that anti-CD3 antibody could partially block
      the sites through which parent antibody (HIT3a) bind to CD3+ Jurkat cells. The
      result of 3H-TdR incorporation showed that the chimeric anti-CD3 antibody could
      stimulated proliferation of peripheral blood mononuclear cells (PBMC) as the
      parent antibody. In this thesis, the results of some experiments indicated that
      the chimeric anti-CD3 antibody expressed in CHO cells was an antibody with native
      biological activity, and it is possible to apply to in clinic in the future.

PMID- 15969079
TI  - [Expression of heat-labile enterotoxin and the strategy of purification and
      storage].
AB  - Heat-labile enterotoxin (LT) from Escherichia coli is a bacterial protein toxin
      with an AB5 hexamer structure. LT is a powerful mucosal adjuvant when co
      administered with soluble antigens. However, its use in mucosal immunity is
      inconvenient because of its low yield and depolymerization during long-term
      storage under normal condition. In this study, we report an efficient expression
      system and optimized purification and storage strategy of LT. A gene encoding LT
      was cloned into the vector pET11c and transformed in E. coli BL21(DE3). By
      growing this strain on modified M9-CAA medium, LT was expressed efficiently.
      About 46mg/L LT could be purified from the supernatant of bacteria lysate. Using
      D(+)-Immobilized galactose column, LT could be purified at a wide pH range with
      various elution buffers. The optimized elution buffers are TEAN (pH 7.3)
      containing 0.3mol/L galactose and carbonate buffer (pH 10.4) containing 0.3mol/L
      galactose. After dried by freeze and placed in 4 degrees C, LT dissolved in TEAN
      (pH 7.3) and carbonate buffer (pH 10.4) were assayed by HPLC. The results
      indicated that the integrity of AB5 hexamer was kept well. LT could undergo long
      term storage under this condition. This was proved to be an optimized strategy of
      LT storage. The results of GM1 binding assay and toxicity assay showed that the
      purified recombinant LT has normal biological character.

PMID- 15969080
TI  - [Screening of Bacillus thuringiensis strains containing vip3A genes and analysis
      of gene conservation].
AB  - Vip3A, a novel insecticidal protein, is secreted by Bacillus thuringiensis (Bt)
      during vegetative growth. Vip3A protein possesses insecticidal activity against a
      wild spectrum of lepidopteran insect larvae. Since the first cloning of vip3A
      gene from Bt, many other vip3A genes have been isolated. To investigate vip3A
      genes contribution to Bt and reflect the revolution relationships, the strains
      containing vip3A genes were screened and gene similarity was analyzed. 114 wild
      type Bacillus thuringiensis (Bt) strains isolated from different regions and 41
      standard Bt strains from the Institute of Pasteur were screened for the vip3A
      genes using PCR amplification. 39 strains including B. thuringiensis subsp.
      kurstaki (Btk) HD-1 were found to contain the vip3A genes. Because acrystallerous
      strain Cry- B derived from Btk HD-1 was proved not to contain vip3A gene, it
      suppose that the vip3A gene may be located at the plasmids. Vip3A proteins
      expressed in these strains were detected with polyclonal antibody by Western blot
      and 4 strains among them were shown not to express the Vip3A proteins. The vip3A
      genes amplified from wild-type Bacillus thuringiensis strains S101 and 611 with
      different levels of activity against lepidopteran insect larvae were cloned into
      pGEM-T Easy vector. Alignment of these 2 putative Vip3A proteins with 6 others
      (Vip3A (a), Vip3A(b), Vip3A-S, Vip3A-S184, Vip83 and Vip3V) in the GenBank data
      base and 2 reported Vip3A proteins (Vip14 and Vip15) showed that vip3A genes are
      highly conservative. The plasmids pOTP-S101 and pOTP-611 were constructed by in-
      serting 2 vip3A genes (vip3A-S101 and vip3A-611) into the expression vector pQE30
      respectively and were transformed into E. coli M15. E. coli M15 cells harboring
      the pOTP plasmids were induced with 1 mmol/L IPTG to express 89 kDa protein.
      Experiments showed that the level of soluble proteins of Vip3A-S101 in E. coli
      M15[pOTP-S101] and Vip3A-611 in E. coli M15 [pOTP-611] were about 48% and 35%
      respectively. Bioassay showed that each of these Vip3A proteins had similar
      toxicity against neonate Spodoptera litura larvae, indicating that some amino
      acids change had little effect on the insecticidal activity of proteins. Although
      vip3A genes are conservative, the unknown insecticidal spectrum is still to be
      brought out. Vip3A genes can be used for the construction of the Bt engineered
      strains and transgenic plants. In addition, vip3A genes are excellent candidates
      for delay of the pest resistance due to the difference of the action model from
      that of Bt delta-endotoxins.

PMID- 15969081
TI  - [Construction of a vector conferring herbicide and pest resistance in tobacco
      plant].
AB  - A binary plant expression vector, pCM12-slm, carrying the aroAM12 mutant gene
      encoding bacterial 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) and the
      Bts1m recombinant gene consisting of 331 N-terminal amino acids of CryIAc and 284
      C-terminal amino acids of CryIAb has been constructed. The truncated Bts1 gene
      was fused with the PR1b signal peptide sequence and expressed in tobacco plants
      under the control of 2E-CaMV35S promoter and the omega (omega) translation
      enhancer sequence from tobacco mosaic virus. The mutant aroAM12 was fused with
      the transit sequence of tobacco EPSPS and expressed in tobacco plants under the
      control of the CaMV35S promoter. Tobacco leaves were transformed with
      Agrobacterium tumefaciens LBA4404 harboring the pCM12-slm plasmid, and the
      transgenic plants were selected directly on medium containing the herbicide.
      Forty glyphosate resistant plants were regenerated, with a transformation
      frequency of 27%. Transgenic plants were initially assessed for glyphosate
      resistance by placing leaf discs on shoot induction media containing the
      herbicide. Rooted plantlets, propagated from selected transgenic tobacco, were
      transferred to soil in a greenhouse and tested for glyphosate resistance by
      spraying them with Roundup at a commercial recommended dose. The glyphosate
      resistance assay indicated that all the transgenic plants showed highly resistant
      to the herbicide. The PCR assay showed that the aroAM12 gene was present in all
      of the 40 T0 transfer plants, and Bts1m genes present in 28 of 40 of the
      transgenic plants. Southern blot analysis further confirmed that the copy number
      of the transgenes varied from one to three copies in different transgenic plants.
      Northern blot and immunodot blot showed that the aroAM12 and Bts1m genes were
      expressed at the transcription and translation levels. Transgenic plants
      containing both the aroA M12 and Bts1m genes were further assessed for insect
      resistance. Tobacco leaves of T0 transgenic plants were infested with tobacco
      bollworm H. assulta larvae for 6 days. The result (table 1) showed that the
      survival rate of insect larvae was between 0-10%, and the growth of insect larvae
      was seriously inhibited, suggesting pCM12-slm as a dual functional vector with
      potential application in breeding of glyphosate and insect resistance transgenic
      plants.

PMID- 15969082
TI  - [Genetically marking of natural biocontrol bacterium Bacillus subtilis strains
      with green fluorescent protein gene].
AB  - The full length sequence of the promoter and gfp gene were obtained respectively
      by PCR with two pairs unique primers PxyF/R and primers gfpF/R, which were
      designed according to the gfp gene and promoter sequence of xylase operon from
      Bacillus subtilis 168, and the DNA template plasmids pHT315-xyIR and pGFPuv.
      Furthermore, the fused translational expression cassette PxylR-gfp was
      constructed using overlapping PCR technique with the primers pair PxyF/gfpR and
      the mixture of above PCR production. After being digested by Kpn I and Sph I ,
      PxylR-gfp expression cassette was inserted into E. coli-B. thuringiensis shuttle
      vecter pHT315 and E. coli-B. subtilis shuttle vecter pRP22, and the resulted
      recombinant plasmids were named as pGFP315 and pGFP22 respectively. Both
      recombinant plasmids were transferred into B. subtilis lab strain 168 and the
      resulted transformants are bright green performance under 365 nm UV light.
      However, only pGFP22 can be introduced into the natural strain B916. The
      transformants containing pGFP22 have bright green performance under 365 nm UV
      light and was named B916-gfp. Antifungal activities testing results proved that
      there is no obvious difference between B916 and the engineered strains B916-gfp.
      Research results also showed that the stability of B916-gfp was 94% after growth
      about 175 generations at 37 degrees C, and the losing rate of plasmid was less
      than 3.5 x 10(-4) per generation.

PMID- 15969083
TI  - [Expression of recombinant human BMP-6 in Escherichia coli and its purification
      and bioassay in vitro].
AB  - To purify the recombinant human BMP-6 protein and to establish its in vitro
      bioassay method. The cDNA encoding the mature peptide of hBMP-6 protein was
      amplified by reverse transcription-polymerase chain reaction (RT-PCR), using
      human placental mRNA as template, and subcloned into the high-expression vector
      pET-15b under the control of T7 lac promoter. The resulting construct, pET-BMP6,
      was then transformed into an Escherichia coli strain BL21 (DE3) for the
      production of recombinant hBMP-6 protein (rhBMP-6). After 4 hours of induction by
      isopropyl-beta-D-thiogalactoside (IPTG), rhBMP-6 (approximately 15kD) was
      expressed and formed inclusion bodies, contributing up to 10% of the total
      bacterial protein. The inclusion bodies were isolated and redissolved in 8mol/L
      urea, and the denatured rhBMP-6 was purified to 95% purity by CM-Cellulose 32 ion
      exchange chromatography (IEC). The osteoinductivity of rhBMP-6 was measured by
      the expression of some of the osteoblast differentiation marker genes in rhBMP-6
      treated C3H10T1/2 cells as reflected by determinations of alkaline phosphatase
      (ALPase) activity and semi-quantitative RT-PCR. At the end of the purification
      process, about 80% of rhBMP-6 formed disulphide-linked homodimers after refolding
      during renaturation. The apparent size of the protein was 30kD on non-reducing
      SDS-PAGE, similar to that of the native form of hBMP-6. The enzyme assays showed
      that the ALPase activity was increased in a dose-dependent manner with the
      treatment of rhBMP-6. After the addition of 300ng/mL of rhBMP-6, the ALPase
      activity of C3H10T1/2 cells increased significantly. The activity of rhBMP-6 used
      was comparable to about 70% of that of the standard hBMP-6 derived from
      eukaryotic cells. RNA extraction data also showed rhBMP-6 stimulated expression
      of osteoblast marker genes, including type I collagen, osterix, and osteocalcin
      in a time-dependent manner. After 5 days of treatment, their level of expression
      was increased to 3 times that of controls. Bone morphogenetic protein (BMP)-6, a
      member of the 60A subgroup of the bone morphogenetic protein (BMPs) family, plays
      a pivotal role in bone formation. Previous evidence showed that BMP-6 is
      selectively up-regulated by estrogen, suggesting its potential role in the
      treatment of osteoporotic fractures, especially for menopausal osteoporosis. Our
      present study demonstrates that the recombinant hBMP-6 produced in Escherichia
      coli is able to induce pre-osteoblastic cells to differentiate into osteoblasts
      in vitro, and analysis of mRNA expression of type I collagen, osterix, and
      osteocalcin can be also a method for measuring the osteoinductivity of BMP. This
      provides the basis for further studies on ectopic bone formation in the body and
      for the development of auxiliary drugs for the treatment of osteoporotic
      fractures.

PMID- 15969084
TI  - [Cloning of human uracil N-glycosylase and its detection in cancer tissues by
      quantitative RT-PCR].
AB  - The uracil in DNA comes from either the misincorporation of dUTP in place of dTTP
      or deamination of cytosine. In the latter case, it can result in a GC to AT
      transition mutation if the uracil is not removed before DNA replication. Base
      excision repair (BER) is a major pathway for removing DNA lesions arising from
      endogenous processes as well as those induced by exposure to exogenous chemicals
      or irradiation. BER is initiated by DNA glycosylases that excise aberrant bases
      from DNA by cleavage of the N-glycosidic bond linking to the base of its
      deoxyribose sugar. Uracil N-glycosylase (UNG) is the enzyme responsible for the
      first step in the BER pathway that specifically removes uracil from DNA. The UNG
      gene undergoes both temporal and spatial regulation mainly at the level of
      transcription. Normally cancer cells undergo over-proliferation and up-regulate
      their UNG during tumorigenesis. In this study we examine the correlation between
      UNG level and carcinogenesis, and explore the possibility of using UNG as a
      marker for cancer diagnosis. Human UNG gene was amplified from the total RNA of
      the human choriocarcinoma cell line, JEG-3, by RT-PCR. After purification, the
      942bp full-length UNG cDNA coding sequence was digested with EcoR I and Sal I,
      and cloned into the digested pET-21 to construct a recombinant vector, pUNG. The
      UNG protein was expressed under the control of T7 promoter in E. coli BL21 (DE3)
      cells induced with IPTG. After ultrasonic treatment, the cell lysate and
      precipitate were analyzed by SDS-PAGE and a 39kD band was detected. The plasmid
      was serially diluted at appropriate concentrations and employed as standards in
      the subsequent quantification. Total RNAs were extracted from 18 pairs of
      clinical samples, each pair contains a sample of esophageal squamous cell
      carcinoma (ESCC) tissue and its surrounding normal esophageal epithelia. The copy
      numbers of UNG mRNA in these RNA samples were determined by real-time
      quantitative RT-PCR using a Lightcycler (Roche). UNG was present in 13 cases of
      ESCC (13/18, n = 18) but absent in all of the normal tissues. The results
      indicated that there was a correlation between high level of UNG expression and
      the carcinogenesis of ESCC.

PMID- 15969085
TI  - [Bacillus thuringiensis helper protein P20 affects the formation of Cry1Ab].
AB  - The Cry1Ab differs most significantly from the other related ICPs by its absence
      of a carboxyl terminus of 28 amino acids including four cysteines; consequently
      it is less stable. We report that the helper protein P20 plays a role in the
      expression and crystallization of Cry1Ab. Three Cry1Ab expression plasmids pT1B,
      pP1B, and pDP1B, were constructed based on the shuttle vector pHT3101. The vector
      pT1B does not contain the p20 gene, pP1B carries p20, and pDP1B contains p20 with
      cry1A(c) promoter. Transformants were obtained by electroporating the plasmids
      into Bacillus thuringiensis acrystalliferous mutant CryB. Western blot
      demonstrated that crylAb was expressed as a 130 kD protein in all the
      transformants, and some of the protein was partially degraded into a 60 kD
      peptide. Quantitative protein analysis indicated that the amount of the 130 kD
      protein varied in the transformants and was in the ratio of 1:1.4:1.5 for PT1B,
      pP1B and pDP1B respectively. For the 60 kD proteins, the ratio was 1:1.1:1.6.
      Microscopic examination revealed that the size of the typical pyramidal crystals
      in the three transformants was in the order of T1B < P1B < DP1B. Bioassay showed
      that T1B, P1B and DP1B were all toxic to the larvae of Helicoverpa armigera with
      similar LC50. This study suggested that P20 plays a role in the expression and
      crystallization of Cry1Ab.

PMID- 15969086
TI  - [Expression and identification of recombinant arresten in Pichia pastoris].
AB  - Arresten as a endogenous inhibitor of angiogenesis originated from the carboxyl
      terminal 223 amino acids fragment of the non-collagen domain in alpha1 chain of
      human collagen IV. In order to get the soluble arresten with biological activity,
      the cDNA of arresten was cloned and expressed in Pichia pastoris. The produced
      arresten cDNA was amplified by PCR using primer P1:5'-AGGCCCCGATGGGTTGC-3',
      primer P2:5'-CTATAAG GCACTTTACGGTTTC-3'. The PCR products was cloned into pGEM-T
      vector, and sequenced. The arresten cDNA from pGEM-T vector was recombined with
      vector pPIC9 as pPIC9-arresten, used to transform E. coli DH5alpha, and the
      inserted arresten cDNA confirmed by agarose electrophoresis and sequencing. pPIC9
      arresten was linearized by Sac I. Pichia pastoris GS115 was treated with PEG1000
      (followed Invitrogen' s specification); transformed with linear recombined pPIC9
      arresten. Pichia pastoris GS115 was culured on MD mediun, single clone was
      selected and the DNA from the single clone was extracted, used as template,
      characterized by PCR using the second pair primers P3:5'-CGCTCGAGAAAAGATCTGTTGATC
      3', P4:5'-GCCCCGG ATCCTTATGTTCTFCTCATACAG-3'. The polynucleotides CTCGAGAAAAGA
      used as marker sequence was inserted into primer P3 for signal peptidase to
      cleave off the signal sequence correctively. The recombined Pichia pastoris GS115
      was selected according to the results of PCR, cultured on MM and MD media and
      then in the BMGY media using methanol as inducer. Expressed arresten was analysed
      by SDS-PAGE. The soluble arresten expressed by Pichia pastoris gave apparent
      molecular weight in SDS-PAGE consistent with that calculated, and in matrigel gel
      it showed inhibitary activity on the tubulation of endothelial cell ECV-304
      induced by tumor cell MDA-MB-435S. These results showesd arresten with biological
      activity is expressed successfully in Pichia pastoris GS115.

PMID- 15969087
TI  - [Preparation and application of gel chip].
AB  - A new method for manufacturing three-dimensional gel film-coated chips was
      described in this paper and its advantages were evaluated by its application. A
      patch of polyacrylamide gel (15mm x 15mm x 20 microm) was fixed on the glass
      surface with Bind-Silane treatment, then activated by glutaraldehyde. The
      aldehyde groups in gel provided reactive sites that allowed covalent
      immobilization of molecules containing amino groups. Oligonucleotides were
      mechanically spotted by GMS 417 Arrayer. After hybridization with Cy-3 labeled
      probes, fluorescence signals of perfect binding can be discriminated from
      mismatched ones. Compared with two-dimensional glass chip, the capacity of
      oligonucleotides immobilized on gel film-coated chip is over 100 times. And the
      gel film-coated chip have lower background and shorter hybridization time.
      Monoclonal antibodys of cytokine IL-4, IL-5, IL-6, IL-7, ANG, I-309 and VEGF were
      also immobilized on the gel film-coated chips to make protein microarrays. After
      incubation with serum of breast cancer patients or normal persons, the microarray
      reacted with biotin-labeled second antibodys of cytokines and Cy-3-labeled
      streptavidin sequentially. Results show IL-4, IL-5, I-309 and VEGF of patients
      have higher expression level than normal persons. This kind of protein
      microarrays can be potentially helpful to clinical diagnosis. Furthermore
      different oligonucleotides or proteins can be performed in parallel in a single
      reaction with minimal amount of binding reagents. Such gel film-coated chips can
      be used widely in the fabrication of oligonucleotides and proteins microarrays.

PMID- 15969088
TI  - [Rapid and efficient expression of foreign genes in mammalian cells by
      baculovirus vectors].
AB  - The baculovirus insect cell expression system has been used extensively for the
      expression of recombinant proteins in insect cells. Recently, reports have
      described that recombinant baculoviruses can transduce a broad spectrum of
      primary and established mammalian cells, which shows the baculoviruses could
      serve as a new gene-transfer vehicle for mammalian cells. In this report, we
      further research the modification of baculovirus vector and the way to deliver
      exogenous gene into mammalian cells. On the base of Bac-to-Bac baculovirus insect
      cell expression system, two recombinant baculoviruses (BacV-CMV-EGFPA, BacV-CMV
      EGFPB) were constructed containing different direction of CMV promoters which
      controll the expression of a reporter gene (EGFP). We found that CMV promoter
      could direct expression of reporter gene in Sf9 cells with relatively low
      efficiency. The culture supernatant of Sf9 cells which have been infected by the
      recombinant baculoviruses for four days were collected and the titers of the
      viruses in culture supernatant were determined by plaque assay on Sf9 cells. The
      HepG2 cells, an human hepatocellular carcinoma cell line, were directly incubated
      with the collected culture supernatant which contains the recombinant
      baculoviruses for 8 hours in 37 degrees C CO2 incubator (moi = 100). Twenty-four
      hours post transduction the efficiencies of gene-transfer and expression were
      analyzed by flow cytometry (FCM) which detect the green fluorescence of
      individual cells. Results show that these two recombinant baculoviruses have
      similar gene-transfer and expression efficiency in HepG2 cells, which means the
      direction of CMV promoters has no effects on reporter gene expression. The
      optimal transduction conditions of incubating the mammalian cells with the
      culture supernatant of Sf9 cells infected by recombinant baculoviruses for four
      days were determined by FCM assay in HepG2 cells. The HepG2 cells inoculated in
      24-well plate (5 x 10(4)/well) were incubated with the culture supernatant (BacV
      CMV-EGFPA, 1.2 x 10(7) pfu/mL) serially diluted by DMEM culture medium containing
      10% FBS and the transduction times ranged from 1 to 24 hours. Twenty-four hours
      post transduction the efficiencies of gene-transfer and expression were analyzed
      by FCM. Results show that incubating the target cells with the 1:1 diluted
      culture supernatant (moi = 50) for 12 hours in 37 degrees C CO2 incubator would
      achieve the highest infection and expression efficiency with the least impairment
      on cell viability. We compared the gene-transfer and expression efficiency of
      recombinant baculovirus in HepG2 and CV1 cells with lipofectAMINE and recombinant
      retrovirus system, results show that under the similar conditions the recombinant
      baculovirus could achieve the highest gene-transfer and expression efficiency
      than the other two systems. So we can draw a conclusion that directly incubating
      the mammalian cells with the culture supernantant of the infected Sf9 cells could
      serve as a very convenient way for rapid and efficient expression of foreign gene
      in mammalian cells.

PMID- 15969089
TI  - [In vitro suspension and bioreactor culture of hematopoietic cells].
AB  - Stirred culture offers a number of advantages over static systems as it maintains
      a stable, homogeneous culture environment and is easy to scale-up. This paper
      focused on the development and application of stirred tank bioreactor to culture
      hematopoietic cells. Preliminary study of stirred culture of hematopoietic cells
      was carried out in cord blood mononuclear cells culture in spinner flask. The
      results showed that the amplification rates of total cell, CFU-GM and BFU-E, with
      the exception of CFU-Mk, were greater in spinner flask than T-flask. The number
      of total cells increased 20 fold after 14 days incubation in spinner flask. The
      amplification rates of CFU-GM, CFU-Mk and BFU-E reached maximum at 10th day, 10th
      day and 7th day respectively, and the maximal amplification rates were 9.2-fold,
      5.5-fold and 2.4-fold respectively, whereas the rate of CD34+ cells in spinner
      flask was (6.7 +/- 4.0)-fold at day 10. These results indicated that the stirred
      culture system is better than the static culture systems for hematopoietic cell
      proliferation. The biocompatibility of cord blood MNC to different types of
      materials used in bioreactors was also tested. The results showed that glass,
      stainless steel 316L and polytetraflouroethylene (PTFE) supported the growth of
      hematopoietic cells well. A higher cell density was reached in stirred
      bioreactors with controlled pH and DO than static culture. These findings
      suggested that the controlled large-scale culture could be used to overcome the
      clinical shortage of hematopoietic cells.

PMID- 15969090
TI  - [On-line monitoring of oxygen uptake rate and its application in hybridoma
      culture].
AB  - On-line analysis and control are critical for the optimization of product yields
      in animal cell culture. The close monitor of viable cell number helps to gain a
      better insight into the metabolism and to refine culture strategy. In this study,
      we use the oxygen uptake rate (OUR) to estimate the number of viable cell and the
      OUR-based feed-back control strategy for nutrients feeding to improve the
      efficiency of cell culture. A hybridoma cell line (HAb18) was cultured in fed
      batch and perfusion model using serum free medium in 5L CelliGen Plus bioreactor
      (NBS Co., American) and 5L Biostat B bioreactor (Braun Co., Germany). The system
      and the method for online monitoring OUR in bioreactors, based on the dynamic
      measurement of dissolved oxygen (DO), were developed. The method of on-line cell
      concentration estimation was established based on the relationship between the
      growth of the hybridoma and the uptake rate of oxygen. This method was then used
      to determine OUR and the concentrations of cell, antibody, glucose, lactate,
      glutamine and ammonia in the bioreactors at given times. The relationship between
      OUR and nutrients metabolism was studied and OUR-based feed-back control
      strategy, which used the state deltaOUR = 0 as the regulation point, was
      established and used to control the rates of nutrients or medium feeding rate in
      the perfusion culture. The results showed that there was close relationship
      between OUR, concentration of live cells, productivity of antibody and
      consumption of glutamine. The sudden decrease in OUR may be caused by glutamine
      depletion, and with different delay times, the viable cell concentration and
      antibody productivity also decreased. The further analysis revealed the linear
      relationship between OUR and the density of live cells in the exponential growth
      phase as qOUR = (0.103 +/- 0.028) x 10(-12) mol/cell/h. These findings can be
      applied to the on-line detection of live cell density. Our study also indicated
      that by adjusting the perfusion rate with OUR-based feed-back control strategy,
      it is feasible to continuously increase in viable cell density and antibody
      concentration in the perfusion culture.

PMID- 15969091
TI  - [Expression of Chinese sturgeon cystatin in yeast Pichia pastoris and its
      proteinase inhibitory activity analysis].
AB  - Cystatin, which widely distributed in both tissues and body fluids of animal and
      plant, was a superfamily of cysteine proteinase inhibitors. It could form
      activity-inhibitor complexes with cysteine proteinases to inhibit the hydrolytic
      activity of proteinases. Cystatin played important roles not only in the
      inhibition of the proteolytic degradation of fish muscle, but also in biological
      defense systems against invaders. To explore the functions of fish cystatin and
      the potential values in fish disease prevention and cure, as well as seafood
      processing, the recombinant yeast strains which could express Chinese sturgeon
      cystatin were constructed. First, the cystatin cDNA of Chinese sturgeon, which
      had been PCR modified, was subcloned into yeast integrated vector pPICZaA. After
      extracted and purified, the recombinant plasmids were linearized by Sac I. The
      yeast Pichia pastoris GS115 strain was transformed by use of the Lithium Chloride
      transformation method, and the recombinant cystatin yeast strains got. After 0.5%
      methanol induction, SDS-PAGE analysis of the culture supernatant indicated that
      the yield of recombinant cystatin was about 215mg x L(-1) with the percentage
      about 73.6%. The recombinant cystatin was purified through Q-Sepharose anion
      exchange chromatography, and the purity reached about 94.2%. The inhibitory
      activity of recombinant cystatin was measured by inhibiting the proteinase
      activity of papain. The results showed that about 1 microg recombinant cystatin
      could inhibit the activity of 15 microg papain. Heat stability assay results
      showed that there was a decrease in inhibitory activity of cystatin with the
      increasing of temperature. When solution of recombinant cystatin was kept at 70
      degrees C for 5min, the inhibitory activity reduced fast. While the recombinant
      cystatin was heated to 90 degrees C for 5min, the inhibitory activity of
      recombinant cystatin was undetected. The inhibitory activity for recombinant
      Chinese sturgeon cystatin was higher than that of CPI (cysteine proteinase
      inhibitor) from seeds of corn, that about 1 microg purified CIP could inhibited
      the activity of 0.278 microg papain. But the heat stability of recombinant
      cystatin is lower than that of the corn CPI. The expression level and the
      activity of recombinant cystatin from yeast Pichia pastoris were higher than
      those from E. coli. Moreover, recombinant cystatin from Pichia pastoris was
      easier to separate and purify. This paper reported that recombinant fish cystatin
      was produced in a highly efficient expression system based on the methylotrophic
      yeast, further work will focus on the function of recombinant Chinese sturgeon
      cystatin to resist fish disease and explore the value of cystatin as a food
      additive to inhibit cysteine proteinases during surimi processing.

PMID- 15969092
TI  - [Characterization of immobilized aflatoxin-detoxizyme].
AB  - Aflatoxins, found in contaminated food, are potent hepatocarcinogen. The
      aflatoxin-detoxiczyme (ADTZ) isolated from the edible fungus Armillariella sp.,
      detoxifies aflatoxin B1 (AFB1). This paper reports on the characterization of
      immobilized ADTZ using a hydrophobic adsorption method. The ADTZ was isolated
      from cryo-homogenated fungus, previously cultivated at 24 - 28 degrees C for 20 -
      30 days, using n-alkyl amino-agar beads. Various adsorption conditions of the
      enzyme to n-alkyl or n-octyl amino-agar beads were carried out. The effects of
      enzyme immobilization on different alkyl amino-agar beads, at different pH values
      (5.5 - 7.5), at different temperature (20 - 40 degrees C) and at different salt
      concentrations were investigated. The enzyme activity was measured at OD360 by
      reacting 133.3 ng/mL of AFB1 at 30 degrees C for 30 min with the immobilized
      ADTZ. The Km value of the immobilized enzyme, determined using Schematic
      Linewearver-Burk plot, is 3.308 x 10(-3) mol/L, lower than that of free enzyme,
      which is 2.16 x 10(-6) mol/L. This indicated the affinity of the detoxiczyme to
      AFB1 decreased after immobilization. The immobilized enzyme activity in oil-phase
      (n-hexane) was also studied with different concentration of water. After the
      treatment of the immobilized ADTZ, the toxin no longer causes liver toxicity in
      the rat toxicity test, no longer causes mutagenicity in Ames test and is no
      longer toxic in the chicken embryo test. Results also indicated that the pH
      stability, the thermostability and the freezing stability of ADTZ were improved
      after the immobilization.

PMID- 15969093
TI  - [Construction of a SV40 promoter specific artificial transcription factor].
AB  - Transcriptions are regulated by transcription factors. Natural transcription
      factors usually consist of at least two functional domains: a DNA-binding domain
      and an effector domain. According to this, novel artificial transcription factors
      are designed to up or down regulate transcription and expression of a target
      gene. The Cys2-His2 zinc finger domain is a DNA-binding module that has been
      widely used as the DNA-binding domain in artificial transcription factors. Each
      zinc finger domain, which comprises about 30 amino acids that adopt a compact
      structure by chelating a zinc ion, typically functions by binding 3 base pairs of
      DNA sequence. Several zinc fingers linked together would bind proportionally
      longer DNA sequences. According to the "bipartite complementary" library
      strategy, a pair of zinc finger phage display libraries were constructed. After
      construction of the libraries, a 9bp sequence (5'-GCAGAGGCC-3') on the promoter
      of SV40 was chosen as a target for next step. After parallel selection, PCR
      amplification, desired fragments recovery, re-ligation, and additional rounds of
      selection, phage enzyme-linked ELISA experiments were performed to identify
      specific binding clones displaying the zinc fingers with predetermined sequence
      specificity to our target sequence. Then two clones with strong ELISA signals
      were chosen to be tested for binding both to its full target site (5'-GCAGAGGCC
      3') and to sites containing single transition mutations. The binding specificity
      of one of the two clones (clone 3) was shown to be fairly good. The three-finger
      DNA-binding domain targeted to SV40 promoter, that is, zinc finger sequences on
      clone 3, was fused to KOX1 suppression domain KRAB and cloned into pcDNA3.1 (+)
      (which expression product was artificial transcription factor). The zinc fingers
      (which expression product was the DNA-binding domain of artificial transcription
      factor) and KRAB domain only (which expression product was effector domain of
      artificial transcription factor) were also cloned separately into the same
      expression vector. All constructs contained an N-terminal nuclear localization
      signal. Every of the vectors (including pcDNA3.1 (+) without inserting sequences)
      were cotransfected with pGL3-Control and pRL-TK and the activity of luciferase
      was used to indicate the function of product from transfected expression vectors.
      Our artificial transcription factor was proved to repress the expression of
      reporter gene efficiently,while with only DNA-binding domain or effector domain
      the repression was not remarkable. By adding different effector domains and
      changing the DNA-binding domain, artificial transcription factor would have a
      wide range of potential applications.

PMID- 15969094
TI  - [Two-dimensional gel electrophoresis of matrix metalloproteinases in subretinal
      fluids].
AB  - In this work, the experimental conditions for two-dimensional gel electrophoresis
      of subretinal fluids (SRF) matrix metalloproteinases were established. The
      conditions tested included the composition of lysis solution and lysis method,
      the composition of rehydration solution and isoelectric focusing program (IEF),
      the composition of equilibration buffer and equilibration process and the
      composition of incubation solution and incubation methods. The main equipments
      used were IPGphor isoelectric focusing system from Amersham pharmacia and PROTEAN
      II xi cell from Bio-Rad, the gel strips used were the 18 cm long, pH 3 - 8 Linear
      immobiline DryStrips. Among the 9 samples analyzed, 2 were PVR-A, 2 were PVR-C1,
      2 were PVR-C2, 2 were PVR-C3 and the remaining one could not be classified
      definitely. The new 2-DE MMPs method is better than Gelatin SDS-PAGE zymograhpy
      method, as it is higher in resolution, sensitivity and reproducibility. The
      experimental results suggested that the four types of MMPs expressed differently
      at different stages of PVR. Two of the MMPs isomers have same molecular weight
      (MW) but different in isoelectic points (pI). The four MMPs are determined to be
      MMP-1, MMP-2, MMP-9 and MMP-9, with MMP-9 has two active forms. In addition, MMP
      9 and MMP-1 may be present in PVR-A samples but not in PVR-C samples, whereas MMP
      2 is present in PVR-C but not in PVR-A samples. These results revealed the
      complex profiles of MMPs' expression in PVR. The new method can be applied to
      test MMPs expression in tissues, cells and other types of samples with a little
      modification in the protocol, and can be followed by mass spectroscopic analysis
      of MMPs.

PMID- 15969095
TI  - [Fermentation behaviors of recombinant Pichia pastoris under inhibited methanol
      concentration].
AB  - Chemostat culture was performed to characterize the growth, substrate consumption
      and the hirudin production, and to disclose their interrelations in the
      fermentation of recombinant Pichia pastoris. The Andrew substrate-inhibited
      growth model is more suitable than Monod model to simulate the growth of Pichia
      pastoris on methanol. Therefore, two stationary states can be obtained in the
      continuous culture at a certain dilution rate because of the substrate inhibition
      on cell growth. The stationary state could be obtained if only the dilution rate
      not more than 0.048 h(-1) in the continuous fermentation. The concentrations of
      cell, methanol and hirudin were constant after 50 h continuous culture with
      dilution rate at 0.04 h(-1). However, it could not be obtained when the dilution
      rate more than 0.048 h(-1) because the other stationary point at S > 0.048 h(-1)
      is unstable. Therefore, it was found that the cell concentration declined and the
      methanol concentration increased from 2.9 g/L to 18.1 g/L within 18h at dilution
      rate 0.06 h(-1). Thus, the fed-batch culture with a constant specific growth rate
      was carried out to disclose the fermentation behavior at high and constant
      methanol concentration in aid of a methanol sensor. The theoretical maximum
      specific growth rate, microm = 0.0464 h(-1), was found under critical methanol
      concentration, Scrit = 3.1 g/L. The growth of P. pastoris was typically methanol
      limited at the methanol concentration S < Scrit. It was, however, inhibited at S
      > Scrit. The maximum specific Hir65 production rate qp was obtained at 0.2 mg/(g
      x h) when methanol concentration and mu were 0.5 g/L and 0.02 h(-1),
      respectively. The specific Hir65 production rate qp increased with the increase
      of mu and S at mu < 0.02 h(-1), and decreased at mu > 0.02 h(-1). The specific
      methanol consumption rate increased with the increase of S when S < 5 g/L, but
      decreased when S > 5 g/L. At last, the high Hir65 production rate 0.2 mg/(g x h)
      was obtained in the fermentation conducted under methanol-limited concentration
      and mu controlled at 0.5 g/L and 0.02 h(-1), respectively, while the specific
      methanol consumption rate is low only at 0.04 g/(g x h), showing the potential
      for the strategy of getting high Hir65 production rate at the low consumption of
      methanol.

PMID- 15969096
TI  - [Multi-epitope DNA vaccines against avian influenza in chickens].
AB  - Multiple epitopes from one or more viruses can be lined up and co-expressed in
      one vector to generate multi-epitopes DNA vaccines. In the study, four
      recombinant plasmids were constructed based on HA and NP gene of avian influenza
      virus (AIV) (H5N1): (1) pIRES/HA, carrying the complete HA gene; (2) pIRES/tHA,
      carrying a truncated HA gene fragment of major neutralizing antigenic epitopes;
      (3) pIRES/tHA-NPep, in which three CTL epitopes of NP gene of AIV were fused to
      the truncated HA from the C-terminal; and (4) pIRES/tHA-NPep-IFN-gamma, which was
      constructed by replacing neo gene in pIRES/ tHA-NPep with IFN-y of chicken. Fifty
      five SPF chickens were randomly divided into five groups and immunized with the
      above four constructs and control plasmid. Each chicken was intramuscally
      immunized with 200 microg plasmid DNA three times in a two-week interval. Two
      weeks after the third immunization, chickens were injected with H5N1 subtype
      avian influenza virus. Before the virus loading no detectable antibodies to HA
      were found in the chicken serum; but high levels of HI antibodies were detected
      in the serum of the survived chickens. The percentages of CD4+ and CD8+ T
      lymphocyte in peripheral blood of immunized chickens increased steadily after the
      vaccination. After virus loading all chickens in the control group died within
      three to eight days, and the survival rates of the four DNA vaccine groups were
      as follows: pIRES/HA, 54.5%; pIRES/tHA, 30%, pIRES/ tHA-NPep, 36.3%, pIRES/tHA
      NPep-IFN-gamma, 50%. These results indicated that multi-epitopes DNA immunization
      can induce immune response and protect chickens from homologous virus loading.

PMID- 15969097
TI  - [Sequence analysis of bacterial transposon in NHX gene of Populus euphratica].
AB  - The United Nations Environment Program estimates that approximately 20% of
      agricultural land and 50% of cropland in the world is salt-stressed. The gene NHX
      (Na+/H+ exchanger) encodes functional protein that catalyzes the countertransport
      of Na+ and H+ across membranes and may play an important role in plant salt
      tolerance. To clone the NHX from the wild plant Populus euphratica collected in
      Tarim basin and Xinjiang Wujiaqu district into a T-vector, designed primer was
      used to amplify 1kb NHX cDNA fragment with RT-PCR. Total RNA was extracted from
      Populus euphratica tissue (plant tissue was collected from Tarim basin and
      Xinjiang Wujiaqu district and stored in liquid nitrogen) according to the Plant
      RNA Mini Kits of Omega. First cDNAs were synthesized from 1 microg total RNA of
      Populus euphratica seedling. A pair of primers were used to perform RT-PCR. The
      amplified DNA fragment was purified and cloned into pMD18-T vector. However, 1kb
      and 2.3kb fragment were obtained from Tarim basin and Xinjiang Wujiaqu district
      and named as PtNHX and PwNHX, respectively. Sequence analysis reveals that the
      cloned PtNHX fragment of Populus euphratica contains partial NHX coding region
      with 98%, 86%, 84% and 80% identity comparing with Atriplex gemelini, Suaeda
      maritima, Arabidopsis thaliana and Oryza sativa, respectively. This analysis
      suggests that NHX gene would be highly conserved in terms of evolution in plant;
      and it also suggests that the NHX gene of Populus euphratica also would have the
      similarity with that of Arabidopsis. It may be of great importance in improvement
      of the plant salt tolerance and breed of crop. At the same time, sequence
      analysis shows that PwNHX gene includes a coding region about 1350bp with 99%
      identity comparing with transposon Tn10 IS10-left transposase of Shigella
      flexneri. On the one hand, the NHX gene may lose its function because it was
      inserted a fragment in coding region. On the other hand, its product may play a
      important role in salt tolerance. Populus grow in saline soil. It speculates that
      it may have other salt tolerance mechanism in Populus. The transposon can be used
      as transposon tagging to clone other genes and it will help us to understand
      farther the salt tolerance mechanism.

PMID- 15969098
TI  - [Induced activity of nitrate reductase by nitrate and cloning of nitrate
      reductase gene].
AB  - Excessive nitrate accumulated in plants affects vegetable quality severely and
      excessive nitrate ingestion would do harm to human health. Assimilatory NADH:
      nitrate reductase (NR, EC 1.6.6.1), a complex Mo-pterin-, cytochrome b(557)- and
      FAD-containing protein, catalyzes the regulated and rate-limiting step in the
      utilization of inorganic nitrogen by higher plants. Enhancing the activity of NR
      is conducive to reduce the concentration of nitrate in plants. The experiments
      were conducted to investigate the activity of nitrate reductase in different
      plant tissues and the relationship between external inducing solution
      concentration and NR activity (NRA) in plant leaves. Six plant seedlings growing
      in solution culture were deprived of an external nitrogen (N) supply for 2 weeks.
      On selected days, three of six plant seedlings were exposed to 50mmol/L NO3- for
      0, 2, 5, 8, 11h, and four of the six plant seedlings were exposed to 0, 10, 30,
      50mmol/L NO3- for 2h. The NRA was determined in vivo at 538nm using
      spectrophotometer. The results showed that NRA increased when those plant
      seedlings were induced by nitrate solution. The change trends of NRA in roots and
      in leaves of cole, pea and tomato were different during treating time. The NRA in
      cole leaves was higher than that in its root and in other two plants and
      increased along with inducing time, but the NRA in bea and tomato was highest
      when the treating time was 8h and 2h, respectively. The highest NRA in leaves of
      three kinds of Chinese cabbages and tomato was induced by different
      concentrations of KNO3 solution. In tomato leaves, the highest NRA was induced by
      10 - 30mmol/L KNO3 solution. In three Chinese cabbages, Brassica chinensis L. cv.
      AJH, XBC and KR-605, the highest NRA was induced by 10, 30, 10mmol/L KNO3
      solution, respectively. The results indicated that the response manners of NRA in
      plants to external nitrate solutions were different. According to these results,
      the level of NR mRNA in plants could be enhanced by nitrate inducement. The total
      RNA was isolated from tomato leaves and root which induced by 30mmol/L KNO3
      solution for 2h, and NR cDNA was obtained by RT-PCR using the specific primers.
      The fragments of PCR products were cloned and sequenced. There are 2736 base
      pairs in the whole cDNA fragment. The deduced protein sequence contains 911 amino
      acids. The NR gene can be fused to the CaMV 35S promoter, then introduced to
      higher plants, such as vegetables. It is hoped to decrease drastically the
      nitrate content of the transgenic plants.

PMID- 15969099
TI  - [Progress in the pathway engineering of ethanol fermentation from xylose
      utilising recombinant Saccharomyces cerevisiae].
AB  - Pathway engineering was the third generation of gene engineering. Its main goals
      were to change metabolic flux and open a new metabolic pathway in organism.
      Application of recombinant DNA methods to restructure metabolic networks can
      improve production of metabolite and protein products by altering pathway
      distributions and rates. Ethanol is the most advanced liquid fuel because it is
      environmentally friendly. Enhancing fuel ethanol production will require
      developing lower-cost feedstock, and only lignocellulosic feedstock is available
      in sufficient quantities to substitute for corn starch. Xylose is the major
      pentose found in lignocellulosic materials and after glucose the most abundant
      sugar available in nature. Recently a lot of attentions have been focused on
      designing metabolic pathway of Saccharomyces cerevisiae in order to expand the
      substrate of ethanol fermentation, because it is a traditional ethanol producing
      strain and has wonderful properties for ethanol industry. However, it can not
      utilize xylose but convert the isomer, xylulose. Many attempts are based on
      introducing the genes in the pathway of xylose metabolism. The further research
      includes overexpressing the key enzyme or decreasing the unimportant flux. The
      sugars in lignocellulose hydrolyzates, therefore, could be efficiently utilized.
      Here, we describe the ethanol pathway engineering progress in ethanol
      fermentation from xylose with recombinant Saccharomyces cerevisiae.

PMID- 15969100
TI  - [Ubiquitin-proteasome pathway and virus infection].
AB  - Ubiquitin is highly conserved 76 amino acid protein found in all eukaryotic
      organisms and ubiquitin-proteasome pathway (UPP) plays a very important role in
      regulated non-lysosomal ATP dependent protein degradation. This pathway
      participates in or regulates numerous cellular processes, such as selective
      protein degradation, cell cycle progression, apoptosis, signal transduction,
      transcriptional regulation, receptor control by endocytosis, immune response and
      the processing of antigens. Nevertheless, roles of UPP in virus infection are
      only beginning to be clarified. Ubiquitin homology has also been found in insect
      viruses. All viral ubiquitin genes encode an N-terminal ubiquitin sequence and 3
      256 amino acids C-terminal peptides. Most of the residues known to be essential
      for ubiquitin function have been conserved in the viral variant. In Autographa
      californica nucleopolyhedrovirus (AcMNPV), viral ubiquitin is attached to the
      inner surface of budded viron membrane by a covalently linked phospholipid and is
      not essential for viral replication. Currently, insect viruses are the only
      viruses known to encode ubiquitin. However, ubiquitin also plays a role in the
      life cycle of other viruses. Host ubiquitin molecules have been found in some
      plant viruses and other animal viruses. Additionally, Africa swine fever virus
      (ASFV) encodes a ubiquitin-conjugating enzyme (E2) and a putative causal link
      between human immunodeficiency virus type 1 (HIV-1) and ubiquitin was established
      by showing that depletion of the intracellular pool of free ubiquitin inhibits
      the virus budding. Further analyses indicated that many retroviruses proteins
      which are required for efficient pinching off the virus bud contain a late
      domain. The core element of the late domain is a proline-rich motif (PPXY) which
      mediates the late domain to be ubiquitinated by cellular proteins. Recently, it
      has been shown that many retroviruses have developed mechanisms to escape the
      cellular immune response, to facilitate virus replication and to promote virus
      assembly and budding via host UPP.

PMID- 15969101
TI  - [Advances in the research of genetic engineering of heavy metal resistance and
      accumulation in plants].
AB  - Using plants to remove or inactivate heavy metal pollutants from soils and
      surface waters provide a cheap and sustainable approach of Phytoremediation.
      However, field trials suggested that the efficiency of contaminant removal using
      natural hyperaccumulators is insufficient, due to that many of these species are
      slow growing and produce little shoot biomass. These factors severely constrain
      their potential for large-scale decontamination of polluted soils. Moreover, both
      the micronutrient and toxic metal content accumulated in crops determine the
      quality and safety of our food-chain. By a transgenic approach, the introduction
      of novel genes responsible for hyperaccumulating phenotype into high biomass
      plants and/or stable crops uptaking minerals as food is a promising strategy for
      the development of effective techniques of phytoremediation and improvement of
      nutritional value of stable food through a viable commercialization. Recently,
      the progress at molecular level for heavy metal uptaking, detoxification and
      hyperaccumulation in plants, and also the clarification of some functional genes
      in bacteria, yeasts, plants and animals, have advanced the research on genetic
      engineering plants of heavy metal resistance and accumulation, and on the
      functional genes (e . g. gsh1, MerA and ArsC) and their genetic transformated
      plants. These studies demonstrated commercialization potentials of
      phytoremediation. In this paper, the molecular approach, effects and problems in
      gene transformation were discussed in details, and also the strategy and emphases
      were probed into the future research.

PMID- 15969102
TI  - [Construction of human MAGE-3 DNA vaccine and its immune effects observed in
      vivo].
AB  - To investigate the antitumor immune responses induced by MAGE-3 DNA vaccine, the
      recombinant mammalian expression plasmid pcDNA3.1/MAGE-3 was constructed by
      ligating MAGE-3 gene, which was amplified by RT-PCR, and the pcD-NA3.1 + vector.
      The recombinant plasmids were transfected into B16 cells by liposome, the
      expression of MAGE-3 was checked by RT-PCR, immunocytochemistry and Western blot.
      Then, 100 ug recombinant plasmids were injected intramuscularly per C57BL/6 mouse
      on 0, 10 and 20 days, with pcDNA3.1 + plasmid and PBS as controls. Splenocytes
      CTLs, the level of antibodies against MAGE-3 the changes of the T lymphocyte
      subsets and the levels of cytokines were checked after 3 times immunization. As a
      result, the mice immunized with pcDNA3.1/MAGE-3 plasmid can produce MAGE-3
      specific immune response. The CTLs kill activities against B16/MAGE-3 cells was
      51.08 +/- 7.41%, and had significant difference (P < 0.01) compared with that of
      pcDNA3.1 + group (8.44 +/- 1.89%) and PBS group (5.76 +/- 1.75%). The titre of
      antibody against MAGE-3 was 1:15, while controls were negtive. The number of CD4
      + CD8 + and the levels of IFN-gamma IL-2 increased significantly after
      immunization with pcDNA3.1/MAGE-3 plasmid as compared with those of control
      groups (P < 0.01). It is concluded that the pcDNA3.1-MAGE-3 DNA vaccine are able
      to induce both cellular and humoral immune responses in vivo.

PMID- 15969103
TI  - [Construction of a secreting prokaryotic shuttle expressing plasmid pBCG-sP-HSP65
      and its expression in Mycobacterial smegmatis].
AB  - To construct the secretive prokaryotic shuttle expression plasmid pBCG-SP-HSP65,
      the signal peptide sequence of antigen 85B amplified from Bacillus Calmette
      guerin (BCG) genome by PCR and the whole HSP65 DNA sequence of human M.
      tuberculosis obtained from the plasmid pCMV-MTHSP65 by PCR were cloned into the
      plasmid pBCG-2100 under the control of the promoter of Heat Shock Protein 70
      (HSP70) from human M. tuberculosis. Recombinants were electroporated into
      Mycobacterial smegmatis and induced by heating. Results of the induced expression
      were detected by SDS-PAGE and the biological activity of the expressed protein
      was tested by Western-blot analysis. Results showed pBCG-SP-MTHSP65 was
      constructed successfully and confirmed by restriction endonuclease analysis, PCR
      detection and DNA sequencing analysis. After it was electroporated into
      Mycobacterial smegmatis and induced by heating, the percentage of expressed 65kD
      protein in Mycobacterial smegmatis detected by SDS-PAGE was 20% in total
      bacterial protein. But the percentage of expressed 65kD protein in recombibinant
      Mycobacterial smegmatis was up to 34.46% in total bacterial protein and 68.56% in
      the total protein of cell lysate supernants, Which demonstrated the recombinant
      HSP65 gene could express in recombinant with high efficiency and the expressed
      proteins were mainly soluble. Western-blot showed that the secretive proteins
      could specially combine with antibody against human M. tuberculosis HSP65.
      Orally, pBCG-SP-HSP65 was successfully constructed; HSP65 gene could express in
      Mycobacterial smegmatis with high efficiency via it. And the expressed proteins
      possess the biological activity. So it provids experimental evidence for the
      application of the recombinant Mycobacterial smegmatis and the development of the
      vaccine against tuberculosis.

PMID- 15969104
TI  - [Non-fused expression of HAb18GEF by reducing stability of translational
      initiation region in mRNA].
AB  - To express the extracellular fragement of hepatoma associated antigen
      HAbl8G(HAb18GEF) in E. coli efficiently in a non-fusing way, the cDNA of HAb18GEF
      gene was inserted into prokaryotic expression vector pET21a + . The secondary
      structure and codon adaptation of translational initiation region (TIR, from-30
      to + 39) in mRNA of recombinant vector HAb18GEF/ pET21a + was predicted
      simultaneously by computer-aided design. Stable Stem-Loop structures and many low
      usage codons were detected in mRNA-TIR of non-optimized recombinant
      HAb18GEF/pET21a + vector. The stability of mRNA-TIR in recombinant
      HAb18GEF/pET21a + vector was reduced with following methods: (1) optimization of
      secondary structure (2) optimization of codon adaptation. These optimization were
      realized by non-continual site-directed mutagenesis without changing any amino
      acid sequence in TIR. After being checked through restriction endonuclease
      digestion and confirmed through nucleotide sequencing, the pre-optimized and post
      optimized recombinant vectors were transformed into competent E. coli JM109-DE3.
      The resulted recombinant clones were selected randomly and induced by IPTG at 37
      degrees C. The induced production of these recombinants was analyzed by SDS-PAGE,
      indirect ELISA, Western blot, and cell fractionation assay. The amount of
      HAb18GEF mRNA was also detected by RNA dot blot between pre-optimized recombinant
      and post-optimized recombinant. The results revealed that recombinant non-fused
      vectors HAb18GEF/pET21a + were successfully constructed and optimized in the
      secondary structure and codon adaptation of TIR respectively. The HAb18GEF was
      expressed efficiently in a non-fusing way in recombinant E. coli by secondary
      structure optimization or codon adaptation optimization. Whereas, no expression
      of HAb18GEF was detected in pre-optimized recombinants. The non-fused expression
      products-HAb18GEF, mainly as inclusion body in E. coli, yielded highly above
      29.3%. A trait of expression HAb18GEF was also detected both in intermembrane
      space and in culture medium due to over-expression and cell leakage. Difference
      in non-fused expression level of HAb18GEF between secondary structure
      optimization and codon adaptation optimization was negligible. No difference in
      amount of transcribed mRNA of HAb18GEF between the pre-optimized and the post
      optimized recombinants was detected. To sum up, it's feasible to express hepatoma
      associated antigen HAb18GEF in a non-fusing way by reducing the stability of TIR
      in mRNA.

PMID- 15969105
TI  - [Optimization of the expression of human DNA topoisomerase I in Pichia pastoris].
AB  - Human DNA Topoisomerase I (hTopo I) has been identified to be an efficient target
      of many effective antitumor drugs. Natural hTopo I is not convenient to be used
      in screening because of its low concentration in cells. In order to fast screen
      new anticancer drugs targeting at hTopo I from natural compounds in vitro, hTopo
      I gene open reading frame (ORF) has been successfully cloned and overexpressed in
      Pichia pastoris. Total RNA extracted from Hela cells was reversely transcripted
      to synthesize cDNA with the hTopo I specific antisense primer and the hTopo I ORF
      was synthesized by PCR. After digestion with EcoR I and Kpn I, the synthesized
      fragment was inserted into pPICZaA, gave rise to pPICZalpha-hTopoI. After
      digestion with Sac I, the lined pPICZalpha-hTopoI was transformed into Pichia
      pastoris strains (KM71, X33 and SMD1168) by electroporation and integrated into
      their genome. After screened on YPDS plates (containing 1000 ug/mL zeocin), the
      high-copy recombinant strains (KM-hTopoI, X33-hTopoI and SMD-hTopol) could
      overexpress recombinant hTopo I, which was fused to the alpha-factor secretion
      signal and could be secreted into the supernatant in the culture. alpha-factor
      could be cleaved from the expressed protein during secretion. A higher activity
      amount of the enzyme was secreted by the particular strain SMD-hTopoI because of
      its absence of proteimase A than by other strains which possess proteinase A
      activity. After optimizing the fermentation conditions, a relatively higher
      enzyme activity in the culture supernatant could be obtained when SMD-hTopoI was
      induced in BMMY (pH7.25) at 20 degrees C , with addition of 0.5% (V/V) methanol
      and 3% (V/V) nutrient liquid every 24h. The enzyme activity reached 43 000 u/mL,
      the yield reached 11 mg/L, achieving approximate 10% of total protein in the
      culture supernatant. SDS-PAGE and Western blot analyses showed that the mass of
      the recombinant hTopo I was 91 kD with no glycosylation.

PMID- 15969106
TI  - [Construction and expression of single chain Fv gene against domain II of human
      VEGF receptor II].
AB  - The genes encoding for the light and heavy chain variable regions (V(H) and V(L))
      has been cloned by RT-PCR from a murine hybridoma that produced monoclonal
      antibody (mAb) Ycom1D3, which was against domain III of human vascular
      endothelial growth factor receptor II (KDRIII) and were then connected to each
      other by a short peptide linker containing 15 amino acids (Gly4Ser)3 using splice
      overlap extensive PCR. The recombinant Ycom1D3-ScFv gene was cloned into the
      expression vector pAYZ and induced to express in E. coli 16C9. SDS-PAGE and
      Western blot analysis showed that the recombinant Ycom1D3-ScFv gene was expressed
      in E. coli 16C9 and the relative molecular weight of the fusion protein is 30kD
      which was consistent with the theoretically predicted value. ScFv expression was
      in the form of an inclusion body and the purified fusion protein was obtained
      after a series of purification steps including cell breakage, inclusion body
      solubilization, TALON metal affinity chromatography and protein refolding. Flow
      cytometric analysis showed that the ScFv fragment can react with human umbilical
      vein endothelial cells (HUVECs) which express KDR on the cell surface. In
      Conclusion, Recombinant Ycom1D3-ScFv gene has been successfully constructed and
      expressed in E. coli 16C9, which could be useful in both diagnostic and
      therapeutic applications.

PMID- 15969107
TI  - [Construction, expression and bioactivity characterization of targeting toxin DT
      VEGF].
AB  - Tumor rapid growth depends on neovascularization. Vascular endothelial growth
      factor, the main mediator during the occurrence and formation of vascularization,
      has specific receptors whose expression rate shows difference of orders of
      magnitude between tumor and the normal tissue, so it can be used to transport
      toxin molecules to the proliferative tumor endothelial and kill cancer cells. In
      our experiment, we constructed fusion protein DT-VEGF by linking diphtheria
      toxin's forward 389 amino acids's gene and VEGF165 via a linker. DT-VEGF is
      expressed in E. coli and purified. Our experiment proves in can kill vascular
      endothelial cells specifically, and the inhibition of neovascularization of
      chicken chorionic membrane is also confirmed.

PMID- 15969108
TI  - [Expression of the human soluble interleukin 4 receptor in methylotropic yeast].
AB  - Interleukin-4 (IL-4) is a pleiotropic cytokine which plays a pivotal role in
      shaping immune responses. IL-4 mediates important proinflammatory functions in
      asthma, including the IgE isotype switch. IL-4 exerts its biological effects
      through binding to its receptor (IL-4R) complex, with the alpha chain as the high
      affinity binding subunit. Soluble IL-4R lacks the transmemberane and cytoplasmic
      domains, so it cannot induce cellular activation. By acting as a decoy to
      circulating IL-4 and neutralize its activity, its high specificity and affinity
      make it ideal as an IL-4 antagonist. Some companies have embarked the clinical
      research for asthma treatment with the sIL-4R and the result revealed well
      therapeutic effect. With RNA extracted from human monocyte as the template, The
      sIL-4R cDNA encoding the extracellular domain of IL-4R a chain was obtained by RT
      PCR. Compared with the sIL-4R encoding sequence in GenBank, the nucleotide
      sequencing analysis indicated that there was a A-->G mutation at 148bp and the
      mutation caused Ile-->Val at 50th amino acid. According to the references,
      numerous polymorphisms have been identified in the IL-4R gene and the Ile50Val
      was the only known extracellular variant of human IL-4R. Then the recombinant
      vector pPIC9K/sIL-4R was constructed, linearized and introduced into Pichia
      pastoris GS115 by electroporation. The recombinant sIL-4R was identified by SDS
      PAGE, Western blot and Ligand binding blot. The SDS-PAGE and Western blot
      analysis showed that the apparent molecular weight of expressed sIL-4R was about
      30kD. And the Ligand binding blot analysis indicated the expressed sIL-4R had the
      biological activity. The sIL-4R, which had the biological activity, was
      successfully secretorily expressed in the Pichia pastoris (GS 115).

PMID- 15969109
TI  - [Molecular cloning of two Rhipicephalus haemaphysaloides haemaphysaloides
      cathepsin L-like cysteine proteinase gene].
AB  - Ticks are obligate ectoparasites and vectors of arboviruses, vickettsiate,
      spirochetes and parasitil protozoa of humans and domestic animals. Immunological
      protection of mammalian hosts against tick infestation has been proposed as the
      most sustainable alternative tick control method to the current use of
      acaricides. The success of this method is dependent on the identification of key
      molecules for use as tick vaccine antigens. Proteolytic enzymes are involved in a
      wide range of cellular processes, thus they can be considered as good target
      antigens for a tick vaccine. In the present study, we used rapid amplification of
      cDNA ends protocol and primers that were designed based on the consensus amino
      acid motifs flanking present in all papain-like cysteine proteinases, to amplify,
      sequence and characterize two Rhipicephalus haemaphysaloides haemaphysaloides
      cathepsin L-like cysteine proteinases, named as cysA and cysB. The full length of
      cysA is 1168bp, encoding a 332 amino acid residue polypeptide with 36.33kD
      predicted molecular mass; the full length of cysB is 1153bp, encoding a 335 amino
      acid residue polypeptide with 37.56kD predicted molecular mass. The consensus
      amino acid motifs flanking presence in both deduced amino acid sequences. And
      both genes show high sequence homology to other tick cathepsin L-like cysteine
      proteinase, so they were identified as members of the cysteine proteinase gene
      family. Expression analysis by RT-PCR revealed that cysA and cysB were expressed
      differently in different periods of tick development.

PMID- 15969110
TI  - [Isolation of 2,4-dichlorophenol degrading bacterium strain and cloning and
      expression of its 2,4-dichlorophenol hydroxylase gene].
AB  - 2,4-Dichlorophenol is toxic and biorefratory organic pollutant. A 2,4
      dichlorophenol degrading bacterial strain GT241-1, identified as Pseudomonas sp.,
      was isolated from soil samples which was collected from drainage area of several
      2,4-dichlorophenol producing factories. Strain GT241-1 had strong 2,4
      dichlorophenol degrading ability, it could decompose 91% 2, 4-dichlorophenol of
      90 mg/L within 48 hours at 25 - 30 degrees C, and could utilize 2,4
      dichlorophenol, 2,4-dichlorophenoxyacetic acid (2,4-D), benzoate and catechol as
      sole carbon and energy source. Southern blot showed that 2,4-dichlorophenol
      hydroxylase gene (dcpA) of strain GT241-1 locates on the about 10kb EcoR I/Xba I
      fragment. This fragment was recovered, linked to the vecter pUC19 and transformed
      into the E. coli DH5alpha. A aim transformant, Z539, was obtained by dot blotting
      from about 1200 transformants. PCR and the sequencing results shew that the whole
      dcpA gene is contained within the 10kb EcoR I /Xba I fragment of pZ539. This
      fragment was shortened to about 2.4kb by HindmIII. The shorted fragment was
      subcloned to vecter pRSET-B to get a transformant BS1-12. The subcloned fragment
      was sequenced. Sequencing results showed that the whole length of the subcloned
      fragment containing dcpA is 2389bp and the nucleotide span of coding region is
      from number 276 to number 2072 (1797 bp), with ATG and TAA as start and stop
      codon respectively. The sequence analysis of dcpA and the deduced amino acid
      encoded by dcpA showed that they are different from the relative sequences
      registered in the GenBank. The subcloned fragment carry the promoter of dcpA,
      this can deduce from the fact that the upflow length of dcpA coding region is
      275bp, and further confirmed by the 2,4-dichlorophenol hydroxylase activity
      measurement results. The 2,4-dichlorophenol hydroxylase activity of transformant
      Z539 and BS1-12 were detected, the results showed these transformants have 2,4
      dichlorophenol hydroxylase activity. By comparison, the activity of these
      transformants were lower than that of the strain GT241-1.

PMID- 15969111
TI  - [Induction of hairy roots of Panax ginseng and studies on suitable culture
      condition of ginseng hairy roots].
AB  - Ginseng is a valuable medicinal plant with ginsenosides as its mian effective
      components. Because ginseng is a perennial plant and has a very strict demand for
      soil conditions, the way of cultivating ginseng by cutting woods is still used in
      China at present and thus forest resources has been extremely destroyed.
      Increasing attention has been paid to the hairy roots induced by the infection of
      Agrobacterium rhizogenes in the production of plant secondary metabolic products
      for the hairy roots are characterized by rapid growth and stable hereditary and
      biochemical traits. That has opened a new way for the industrial production of
      ginseosides. However, there is little report for such studies from China. In this
      paper, hairy roots of ginseng were induced from the root explants of two-year-old
      ginseng by Agrobacterium rhizogenes A4 with directly inoculating. The transformed
      hairy roots could grow rapidly on MS medium and 1/2 MS medium without hormones.
      The cultured clones of the hairy roots were established on a solid 1/2 MS medium.
      After 4 - 5 subcultures the hairy roots still maintained a vigorous growth. A
      pair of primers were designed and synthesized according to the analytical results
      of RiA4TL-DNA sequence by Slightom et al . 0.8kb rolC was obtained by PCR using
      the genome DNA of hairy root of ginseng. Transformation was confirmed by PCR
      amplification of rolC genes from the hairy roots of P. ginseng. Growth rate of
      hairy roots on liquid medium increased by 2 times then that of the solid medium.
      The growth of the hairy roots can be divided into three stages: high speed in the
      first two weeks, middle speed in the 3 - 4 weeks and low speed hereafter.
      Changing the culture solution at 2 weeks regular intervals is conductive to
      maintaining the rapid growth of the hairy roots. By means of determination for
      specific growth rate and ginsenosides content, the high-yield hairy root clone
      R9923 was selected. The content of monomer gisenoside of Rg1, Re, Rf, Rbl, Rc,
      Rb2 and Rd in hairy root clone R9923 was determined by the HPLC. The total
      ginsenosides content in the hairy toot clone R9923 came up to 15.2 mg/g. The
      suitable culture conditions for ginseng hairy roots growing were 1/2 MS liquid
      medium (30 g/L glucose), in a shaker at 110 r/min, changing the culture solution
      at 2 weeks and subculture time 4 weeks. In the liquid fermented culture of 2L
      medium, the yield of the hairy roots could amount to 270.10 g in 4 weeks. The
      industrial production of ginsenosides has been preliminarily realized. Effect
      factors on biomass and ginsenosides content such as culture volume, inoculation,
      in steps cultural technology at the scale-up process of hairy roots culture were
      also explorated. Our results have laid a foundation for defining optimum culture
      manner for large-scale cultivation and large-scale production of ginsenosides.

PMID- 15969112
TI  - [Protoplast culture and plant regeneration of the methionine resistant variant of
      Astragalus melilotoides Pall].
AB  - An efficient protocol for plant regeneration from protoplasts of the methionine
      resistant variant of Astragalus melilotoides was established. The friable calli
      induced from internode segments of variant plants were used for protoplast
      preparation. The protoplasts were isolated through enzyme digestion. Calli were
      formed after sustained divisions of protoplasts. High frequency of shoot
      differentiation was obtained from the protocalli on differentiated medium. The
      effects of different media, culturing methods and plating densities on protoplast
      divisions and plant regeneration were studied. The results show that agarose
      beads culture method, KM8p medium supplemented with 1.0 mg/L 2,4-D, 0.5mg/L 6BA,
      0.3 mol/L mannitol, 2% (W/V) sucrose and 500 mg/L casein hydrolysate at a plating
      density of 3 x 10(5)/mL are the appropriate conditions for protoplast division of
      the methionine resistant cell line. The division frequency is over 38%. The
      protoplast-regenerated plants still preserve resistance to methionine and
      ethionine.This research builds up the foundation for the resistant cell line as a
      parent of somatic hybridization.

PMID- 15969113
TI  - [Recovery and purification of monoclonal antibody producted by continuous
      perfusion culture using expended bed adsorption].
AB  - Monoclonal antibody producted by continuous perfusion culture was recovered and
      purified by expended bed adsorption chromatography. A packed bed column XK16/20
      was used for method scouting with Streamline SP adsorbent. Two expended bed
      columns Streamline-25 and -50 were used for method optimization and pilot scale
      experiment, respectively. The recovery yield of monoclonal antibody was above 90%
      in a 5 - 7 fold enhanced purity and 10 fold increased concentration. According to
      the different concentration of monoclonal antibody in cell culture broth, about
      18 - 50L fluid can be treated in a single cycle. MAb purification from lab scale
      (400mg per cycle) to a small pilot scale (2g per cycle) has been achieved.
      Compared with packed bed adsorption, the preparation cycle was half shortened,
      and the cost of production and the complexity of process were decreased markedly.
      It has been proven that a purification process based on expended bed adsorption
      technique is simple, efficient and economical.

PMID- 15969114
TI  - [Characterization and gene cloning of the endoglucanase from Pseudoalteromonas
      sp. DY3 strain].
AB  - A bacteria strain DY3 with high endoglucanse activity was isolated from deep sea
      sediment sample ES0109. The 16S rDNA sequence of DY3 exhibits identity of 99%
      with those of the same genus bacteria Pseudoalteromonas citrea and
      Pseudoalteromonas elyakovii . The celX gene of DY3 obtained by PCR method is
      1479bp in length and encodes a protein of 492 amino acids. The protein encoded by
      celX gene exhibits 95% sequence identity with endoglucanase CelG from
      Pseudoalteromonas haloplanktis. There are two modules in the deduced amino acids
      sequence, a catalytic domain of glycosyl hydrolases family 5 at the N terminal
      and a carbohydrate binding domain at the C terminal which was linked to catalytic
      domain by a short linker. The optimal temperature of CelX is 40 degrees C and the
      optimal pH was between 6 and 7.

PMID- 15969115
TI  - [Study on the reconstitution in vitro and photochemical activities of phytochrome
      from the Synechocystis sp. PCC6803].
AB  - Genomic DNA sequence analysis of phytochrome like photoreceptors in a number of
      bacteria revealed several open reading frames (ORFs) encoding proteins with amino
      acid sequences homologous to plant phytochromes. The phytochrome like
      photoreceptors, collectively called bacteriophytochromes, contain an N-terminal
      domain homologous to the chromophore-binding domain (CBD) of higher plants and a
      C-terminal domain of histidine kinase domain( HKD). Due to their simple
      structure, bacteriophytochromes broaden the view of phytochrome evolution and
      provide us with a simple model to investigate phytochrome-mediated light signal
      in higher plants. In this report, the bacteriophytochromes from Synechocystis sp.
      PCC6803 were investigated. The gene cph1 and its fragment cph1 (C-435) were
      isolated from the Synechocystis sp. PCC6803 genomic DNA by polymerase chain
      reaction(PCR) using specific primers. Then, the genes were cloned with the vector
      pBluescript, yielding plasmids pBlu-cphl and pBlu-cph1 ( C-435), before they are
      subcloned with the vector pET30, using the EcoRV and Xho I restriction sites.
      pBlu-cph1, pBlu-cph1 (N-435) were cleaved with Sma I and Xho I, and the released
      genes were ligated to the pET30a fragment. The E. coli [strain BL21 (DE3)] cells
      containing recombinant pET30a were grown in medium RB at 20 degrees C, and
      harvested 6 h later after induction with isopropyl thio-beta-D-galactoside
      (IPTG). Then, reconstitution systems were employed to study the characteristics
      of the genes. In the reconstitution system, autoassembly of aprotein of
      phytochrome with PCB was investigated. The chromophore addition was an
      autocatalytic process. Reconstitution products were red/infrared (R/FR)
      photochromic, which was similar to that of the phytoehrome in higher plants. How
      ever, the spectral change ratios (deltaAmax/deltaAmin) of the two fragments
      differed from each other. It was also shown that PCB was covalently bound to apo
      protein via Zn2+ fluoresc ence SDS-PAGE. After irradiation by light of 700 nm,
      the maximum absorption spectrum o f holo-Cphl was 650nm. The absorption of it
      after denaturatior in the dark with ur ea in the presence of hydrochloric acid
      (pH = 2) was 660nm, which was similar with th at of cis-PCB. In addition, after
      irradiation by light of 650nm, the maximum absorption spectrum of holo-Cph1 was
      700nm. The absorption of it after denaturation in the dark with urea in the
      presence of hydrochloric acid (pH = 2) was 600nm, which was similar with that of
      trans-PCB. The result showed that the photochromism of phytochrome resulted from
      the isomerizaation of chromophore (PCB in this report). The reconstitution of
      Cph1 (C-435) under the same condition supported the conclusion. Fluorescence
      emission spectrum of the products suggested that bacteriophytochrom e structure
      with cis-PCB was more stable than that with trans-PCB. The new reconstitution
      system in this report sets a base for the application of phytochrome as
      photochromic biomaterials in biosensors. In addition, phytochrome shows great
      potential in food, cosmetic and biological engineering, etc.

PMID- 15969116
TI  - [Influence of wall polymer and preparation process on the particle size and
      encapsulation of hemoglobin microcapsules].
AB  - Methoxypoly (ethylene glycol)- block-poly (DL-lactide) (PELA) microcapsules
      containing bovine hemoglobin (BHb) were prepared by a W/O/W double emulsion
      solvent diffusion process. The P50 and Hill coeffcient were 3466 Pa and 2.4
      respectively, which were near to the natural bioactivity of bovine hemoglobin.
      The results suggested that polymer composition had significant influence on
      encapsulation efficiency and particle size of microcapsules. The encapsulation
      efficiency could reach 90% and the particle size 3 - 5 microm when the PELA
      copolymer containing MPEG 2000 block was used. The encapsulation efficiency and
      particle size increased with the concentration of PELA. Increasing the
      concentrations of NaCl in outer aqueous solution resulted in the increase of
      encapsulation efficiency and the decrease of particle size. As the concentration
      of stabilizer in outer aqueous solution increased in the range of 10 g/L to 20
      g/L, the particle size reduced while encapsulation efficiency was increased,
      further increase of the stabilizer concentration would decrease encapsulation
      efficiency. Increasing of primary emulsion stirring rate was advantageous to the
      improvement of encapsulation efficiency though it had little influence on the
      particle size. The influence of re-emulsion stirring rate was complicated, which
      was not apparent in the case of large volume of re-emulsion solution. When the
      wall polymer and primary emulsion stirring rate were fixed, the encapsulation
      efficiency decreased as the particle size reduced.

PMID- 15969117
TI  - [Studies on in vitro capacitation of goat spermatozoa by heparin treatment].
AB  - Systematical studies are lacking on the influencing factors and mechanisms of the
      heparin enhanced sperm capacitation, although many studies have shown that
      heparin enhanced sperm capacitation. The effect of heparin concentration and
      exposure time, incubation temperature and co-culture with oviductal epithelial
      cells or cumulus cells on goat sperm capacitation were investigated in this
      study. The motility, membrane and acrosome integrity and capacitated percentage
      of goat spermatozoa were assessed after different heparin treatments, and rates
      of fertilization and embryo cleavage were compared after in vitro insemination of
      oocytes with spermatozoa capacitated by different heparin treatments. The major
      results are summarized as follows: 1) When spermatozoa were capacitated with
      heparin at 5, 10, 25, 50 and 100 microg/mL for 45 min, 50 and 100 microg/mL
      heparin treatments produced the highest capacitated percentages of 55% and 56%,
      respectively, but the percentage of spermatozoa with intact acrosomes in the 100
      microg/mL heparin treatment decreased significantly (P < 0.05) in comparison with
      that in the control group, indicating that the optimal heparin concentration for
      goat sperm capacitation would be 50 microg/mL. 2) Capacitated percentage of
      spermatozoa increased with extension of treatment time when goat sperm were
      treated with 50 microg/mL heparin for 0, 10, 20, 30, 45, 60 or 120 min. Although
      heparin treatments for 45 to 120 min did not differ significantly (P > 0.05) in
      capacitated sperm percentages, sperm motility and membrane integrity decreased
      significantly when treated with heparin for 120 min. This suggested that the
      optimal exposure time of heparin at 50 microg/mL for goat sperm capacitation
      would be 45 to 60 min. 3) Significantly higher capacitated percentages of
      spermatozoa were obtained when goat sperm were treated at 42 and 38.5 degrees C
      than at 15 and 37 degrees C, but sperm motility and acrosome integrity were
      significantly lower when spermatozoa were treated at 42 degrees C than they were
      treated at other temperatures. Temperature of 38.5 degrees C would, therefore, be
      the optimal temperature for goat sperm capacitation. 4) The capacitated
      percentage of spermatozoa was significantly higher when goat sperm were co
      cultured with oviductal epithelial cells than when treated with heparin alone or
      co-cultured with cumulus cells, but sperm motility and membrane and acrosome
      integrity did not differ significantly among the three treatments. Rates of
      fertilization (91.3%) and cleavage (72.2%) were significantly higher in the
      oviductal epithelial cell co-culture group than those in the heparin alone group.
      This indicated that co-culture with oviductal epithelial cells significantly
      enhanced goat sperm capacitation by heparin treatment.

PMID- 15969118
TI  - Purification and characterization of recombinant human anti-HAV monoclonal
      antibody.
AB  - In order to obviate the drawbacks of plasma immunoglobulins, the whole molecular
      recombinant human anti-HAV (hepatitis A virus) monoclonal antibody (anti-HAV IgG)
      produced and secreted by rCHO cells was purified and its physicochemical
      properties were extensively characterized. The rCHO cells were cultured in serum
      free medium and the supernatants were collected. The recombinant human IgG
      molecules were sequentially purified by ultrafiltration, rProtein A Sepharose
      Fast Flow affinity chromatography, ion exchange chromatography and diafiltration.
      In affinity chromatography, prior to the target protein elution, an intermediate
      high salt wash step was inserted, different pH and salt concentrations were
      evaluated for the capacity of removing host cell DNA. The yield of the downstream
      purification process was approximately 40%. The purity of anti-HAV IgG thus
      generated was assayed with SEC-HPLC method, integration result showed that the
      monomeric IgG content was more than 99%. Western-blot was carried out with AP
      antiHuman IgG (Fab specific) and AP-antiHuman IgG (Fc specific) respectively, the
      blot result demonstrated that the anti-HAV IgG is human antibody with Fab and Fc
      structure. The specific anti-HAV activity determined by ELISA was 100 IU/mg, with
      anti-HAV immunoglobulin as the working standard reference. Ligand leakage in the
      eluate of the affinity column was approximately 32 ng/mg IgG, while after further
      purification steps, it was decreased to less than 2 ng/mg IgG. Residual host cell
      DNA was monitored with solid dot blot assay, DNA can be removed effectively with
      intermediate high salt wash step in the affinity chromatography. Free sulfhydryl
      content of anti-HAV IgG was assayed with fluorescent spectrophotometer, the low
      molecular weight bands appeared in non-reducing SDS-PAGE may be caused by the
      presence of free sulfhydryl. The endotoxin content was less than 1EU/ mg examined
      by standard LAL test procedures. Anti-HAV IgG prepared with this process is able
      to fulfill the regulatory requirements of State Food and Drug Administration for
      recombinant products.

PMID- 15969119
TI  - [Particulate recombinant hepatitis E virus capsid protein and its antigenicity
      and immunogenicity].
AB  - An E. coli expressed recombinant antigen NE2 was reported to aggregate into homo
      oligomer, and can induce protective antibodies on rhesus monkey, but its
      immunogenicty was much weak after being purified. In this study, three N-terminal
      extension mutant of NE2 were expressed in E. coli, one of which named HEV 239 was
      found to aggregate into particle. HEV 239 antigen had good reactivity with sera
      of hepatitis E patients. The reactivity of HEV 239 against neutralization
      monoclonal antibody 8C11 was similar as NE2 antigen, while the reactivity of it
      against another neutralization monoclonal antibody 8H3 is much better than NE2
      antigen, which indicated better antigenicity of HEV 239 than NE2. The diameter of
      purified HEV 239 particulate antigen was between 15 nm to 30 nm. The ED50 of
      immunization of HEV 239 particle adsorbed by aluminum adjuvant to BALB/c mice was
      between 0.08 microg to 0.25 microg. In contrast, the seraconversion rate of mice
      immunized by NE2 antigen adsorbed by aluminium adjuvant was only 25% on 60 microg
      vaccination. These results suggested that HEV 239 antigen particle has better
      immunogenicity as well as antigenicity than those of NE2 antigen, so it is a
      better vaccine candidate against HEV.

PMID- 15969120
TI  - [Effects of bkdAB interruption on avermectin biosynthesis].
AB  - In this study, Streptomyces avermitilis Bjbm0006 which produces four avermectin B
      components was used as an original test strain. A replacement plasmid containing
      a gene cluster bkdAB (branched-chain alpha-keto acid dehydrogenase gene) involved
      in the biosynthesis of avermectin B in S. avermitilis Bjbm0006 was constructed by
      means of PCR technique and then named as pHJ5821 (pHZ1358::bkdAB&erm). A
      recombinant strain Bjbm5821 was obtained after the gene cluster was interrupted
      by double crossover. This strain was tested in laboratory conditions and analysed
      by PCR using the total DNA as template. The HPLC analysis showed that the strain
      Bjbm5821 synthesized the same 'a' components Bla and B2a as the original strain
      did. However, It lost the ability for the production of 'b'components for example
      B1b and B2b. A novel compound was detected in fermentation products. The results
      of present study suggests that the production of gene cluster bkdAB may play a
      main role similar to alpha-ketoisovaleric acid dehydrogenase in the pathway of
      avermectin synthesis.

PMID- 15969121
TI  - [Expression of N domain of chromogranin A in Bacillus subtilis and its antifungal
      activity].
AB  - Chromogranin A (CGA) is a soluble protein existed in most secreted cells and
      neurons. It was recently found that the bovine CGA N terminal region has
      vasoinhibitory, antibacterial and antifungal activities. Since the need for
      effective antifungal agents increases in parallel with the expanding number of
      immunocompromised patients at risk for fungal infections, it becomes imperative
      to find antifungal compounds with low toxicity toward mammalian cells. To study
      the antifungal activity of CGA N terminal region, the DNA fragment encoding for
      the N terminal 1-76 amino acid sequence (CGA1-76) of human CGA was amplified by
      PCR technique. After DNA sequence analysis, the amplified DNA fragment was cloned
      into the Bacillus subtilis inducible and expression vector pSBPTQ constructed in
      this study and the resultant plasmid pSVTQ was then transformed into triple
      protease deficient Bacillus subtilis strain DB403 competent cells. The
      transformants was screened on LB plates containing 10 microg/mL kanamycin. The
      positive transformant DB403 (pSVTQ) was grown on kanmycin containing 2 x MSR
      medium and sucrose was added to 2% final concentration for induction after 2h
      cultivation. The culture supernatant was used to run SDS-PAGE. The result of SDS
      PAGE showed that the CGA1-76 was expressed by sucrose induction and the expressed
      product secreted into the medium with a yield of 5 mg/L. The expressed product
      reacts specifically with mouse anti CGA47-68 monoclonal antibody. The antifungal
      activity of the expressed product was examined by adding the culture supernatant
      to the fungal spore or Candida albican suspensions at appropriate proportion and
      found that the recombinant human CGA1-76 produced in Bacillus subtilis inhibits
      the growth of Fusarium sp. Alternaria sp. and Candida albican at the
      concerntration of 4 micromol/L. These results demonstrate that human CGA1-76 has
      expressed in Bacillus subtilis and the expressed product is immunogenic and has
      the antifungal activity.

PMID- 15969122
TI  - [Measurement of intracellular pH in long-chain dicarboxylic acid-producing yeast
      Candida tropicalis and its growth activity].
AB  - Intracellular pH (pHi) has an important influence on the metabolic activity of
      cells or cellular processes. The intracellular pH (pHi) of long-chain alpha,omega
      dicarboxylic acid-producing Candida tropicalis was determined by fluorescence
      technique using a pH-sensitive fluorescent probe 5(6)-carboxyfluorescein
      diacetate. Optimal loading conditions of the fluorescent probe into the cells
      were experimentally determined. Effects of extracellular pH and carbon sources
      for growth on pHi in the cell grown in a flask were studied; the results
      indicated that extracellular pH has a slight influence on pHi, whereas carbon
      sources such as sucrose, glucose, acetic acid, and n-tridecane showed moderate
      influences. Further work on the relationship between the cell growth activity and
      pHi was carried out in a 5 L bioreactor. The time course of specific rates of the
      cell growth, glucose consumption, CO2 production, and pH gradients across cell
      plasma membrane were plotted, where the cell growth was improved by the higher
      pHi at 8 - 12 h. The measured pHi values were varied from 5.72 to 6.15 at medium
      pH 6.0 in which glucose and sodium acetate were used together as carbon source.
      The investigation of pHi can be helpful for understanding its effects on the
      kinetics of the metabolic steps involved in the synthesis rate of alpha,omega
      dicarboxylic acid and alpha,omega-dicarboxylic acid transport across plasma
      membranes.

PMID- 15969123
TI  - [Study on the repeated batch fermentation of lipase by immobilized Rhizopus].
AB  - Repeated batch fermentation with Rhizopus arrhizus immobilized by polyurethane
      was optimized in details including the time to replace, the volume of the
      replaced medium and the optimal composition of the medium to replace. Immobilized
      cells showed stability for repeated use. Immobilized cells could be used for 9
      batches, lasting 140h in flask and 6 batches in 5L fermenter when the substitute
      culture medium consisted of (%): soybean flour 3.0, earthnut oil 0.5 and the
      liquid was replaced by 40% . The time for fermentation was reduced largely and
      the lipase productivity was 3 - 6 times as high as that in batch fermentation.

PMID- 15969124
TI  - [Immobilization and stabilization of papain on SiO2 particles containing amine
      groups].
AB  - Numerous approaches and materials have been explored for preparation of
      immobilization enzymes because they have considerable advantages over enzyme in
      bulk solution. Among present enzyme carriers inorganic materials have lower cost
      and more stability than organic materials. But the present inorganic materials
      contain less active sites and have to undergo some complicated processes before
      binding enzyme. So it is necessary to explore a new kind of inorganic enzyme
      carrier. Papain, a well characterized thiol protease kinetically and
      structurally, is a suitable model to compare the efficiency of various
      immobilization procedures. SiO2 particles containing amine groups were
      synthesized by synchronous hydrolysis of tetraethylorthosilicate (TEOS) and N-(2
      aminoethyl)-3-aminopropyltrimethoxysilane (AEAPS) in W/O Microemulsion of Triton
      X-100/cyclohexane/ammonium hydroxide system. The obtained particles have a
      diameter range from 0.3 microm to 0.5 microm, and their average size is 0.37
      microm and can be controlled by adjusting water to surfactant molar ratio and
      water to TEOS and AEAPS molar ratio. Compared with traditional porous silica
      beads, these particles contain much more amine groups and their amine group
      content can be easily changed in the process of synthesis. Papain was immobilized
      on the particles which were treated by glutaraldehyde with covalent method. The
      optimum immobilization conditions of enzyme were as follows: enzyme load was 15
      mg/g carrier, pH was 6.5. The pH and temperature optima were 6.5 and 70 degrees C
      for immobilized enzyme. All above indicate this kind of particle can be a good
      enzyme immobilization carrier.

PMID- 15969125
TI  - [Gene modification and high prokaryotic expression of porcine interferon alpha
      1].
AB  - There are many E. coli rare codons in the gene of porcine interferon alpha-1. In
      order to obtain high expression of poIFN-alpha1 in E. coli, the cDNA encoded
      poIFN-alpha1 mature protein was synthesized using biased codons of E. coli
      without changing the original amino acid sequence and the terminator was changed
      as TAA. At the same time, Adenine and Thymine were used to the largest extent
      near the 5' terminus of poIFN-alpha1 mature protein gene. The synthesized gene
      was inserted into the Eco RI and Sal I site of the expression vector pRLC
      resulting pRLC-poIFN-alpha1. The poIFN-alpha1 is highly expressed in E. coli
      DH5alpha when the induction was carried out at 42 degrees C . The expressed poIFN
      alpha1 account for 24.5% of the total cellular proteins and existed as inclusion
      body. The poIFN-alpha1 inclusion body was dissolved in 6mol/L guanidine chloride
      contained DTT and subsequently the denatured poIFN-alpha1 was re-natured by
      dilution in refolding buffer containing GSH and GSSH. In the present study it was
      found that the denatured poIFN-alpha1 was most efficiently re-natured in
      refolding buffer containing 1 mol/L guanidine chloride. In order to obtain pure
      protein, the concentrated re-natured poIFN-alpha1 was purified by Sephacryl S-200
      chromatography. As a result, the purified poIFN-alpha1 is verified to be of high
      cytokine activity by inhibiting the cytopathic effect of vesicular stomatitis
      virus in MDBK cells, which is about 6.4 x 10(6) u/mg. This study paved the way
      for large-scale production of recombinant poIFN-alpha1 and its usage in virus
      disease control of pigs.

PMID- 15969126
TI  - [Xylitol production from corn cob hemicellulosic hydrolysate by Candida sp].
AB  - Xylitol, a five-carbon sugar alcohol, has many interesting applications in the
      food, pharmaceutical, and odontological industries, owing to its high sweetening
      power, its anticariogenic properties, and its insulin-independent metabolism. The
      bioconversion of detoxified hemicellulosic hydrolysate to xylitol by
      microorganisms could be a cheaper alternative to the current chemical process,
      since it is a simple process, with great specificity and low energy requirements.
      However, the success of fermentations for xylitol production depends on the
      productivity of the strain and its tolerance to different toxic or inhibitory
      compounds existing in the hydrolysates. In addition, a number of culture process
      parameters proved to have significant effects on xylitol production in
      hemicellulosic hydrolysate media. One of the most important control variables in
      this bioconversion is the aeration level, which affects the biochemical pathways
      in the xylose metabolism. The production of biomass is favored by aerobic
      conditions, while under anaerobic conditions xylose cannot be assimilated by
      yeast, whereas xylitol is formed in oxygen-limited incubation conditions. An
      adapted Candida sp. with enhanced resistance to the inhibitors in the hydrolysate
      can directly ferment the simply detoxified corn cob hemicellulosic hydrolysate to
      xylitol. In the present study, the combined effects of shaking speed, C/ N ratio,
      initial pH, and inoculum level on the fermentation of corn cob hemicellulosic
      hydrolysate to xylitol by an adapted Candida sp. were investigated using an
      orthogonal experimental design in flask. As a result, the optimum fermentation
      conditions were as follows: 180 r/min, a C/N ratio of 50, initial pH 5.5, and an
      inoculum level of 5% (volume ratio). Moreover, the optimum concentration factor
      of hydrolysate varied between 3.0 and 3.72 was obtained. Based on these results,
      in order to evaluate the effect of aeration rate on the fermentation of corn cob
      hemicellulosic hydrolysate to xylitol in fermentor, batch fermentations were
      carried out in a 3.7 L stirred fermentor using four different aeration
      strategies, including three kind of two-stage aeration strategies, which provided
      relatively high aeration rate in the early stage but reduced it in the later
      stage, and including a one-stage aeration strategy provided a constant aeration
      rate. With respect to xylitol yield, the results indicated that two-stage
      aeration strategy was significantly superior to one-stage aeration strategy. The
      highest xylitol yield (0.75 g/g) was obtained with oxygen supply strategy C (3.75
      L/min for first 24 h, then lowered it to 1.25 L/min, 2.5 L fermentation medium
      was employed). In this process, without extensive detoxification of hydrolysate,
      an adapted Candida sp. can efficiently ferment the simply treated corn cob
      hemicellulosic hydrolysate to xylitol under the optimized fermentation
      conditions. This work should help the development of an efficient process for
      producing xylitol from corn cob hemicellulosic hydrolysate on a larger scale by
      bioconversion.

PMID- 15969127
TI  - [The mechanism of Stat3 nuclear import].
AB  - In order to investigate the mechanism of stat3 nuclear import. positioned a
      characterized NLS of the SV40 large T antigen into Stat3-GFP, Dstat3-GFP
      respectively between the C-terminus of Stat3 and the N-terminus of GFP to create
      Stat3-NLS-GFP and Dstat3-NLS-GFP. With NLS-GFP as the positive control,
      Expression of the Stat3-NLS-GFP without IL-6 stimulation and Stat3-GFP with IL-6
      stimulation resulted in a predominantly nuclear localization in 293T cell.
      Expression of Stat3-GFP and Dstat3-NLS-GFP without IL-6 stimulation resulted in
      predominantly cytoplasm localization in 293T cell. The results suggest that
      latent Stat3 is not anchored in the cytoplasm, and that nuclear localization in
      response to IL-6 is facilitated by gain of an NLS function.

PMID- 15969128
TI  - [Effects of veratryl alcohol and tween 80 on ligninase production and its roles
      in decolorization of azo dyes by white-rot basidiomycete PM2].
AB  - Basidiomycete PM2, a lignin-degrading white rot fungus, produces lgnin peroxidase
      (Lip) and manganese peroxidase (Mnp) in nutrient nitrogen limited liquid
      cultures. This fungus was selected for its ability to decolorize azo group of
      dyes. In order to improve production of the peroxidases and rapid dye
      decolorizing activity by basidiomycete PM2, the addition of veratryl alcohol or
      Tween 80 to nutrient nitrogen limited liquid cultures were tested. It was found
      to have a large stimulatory effect on Mnp activities and decolorization rate of
      azo dyes. A maximum Mnp activities of 254.2 u/L with veratryl alcohol and 192.2
      u/L with Tween 80 were achieved respectively. These values were about 3.4-fold
      and 2.5-fold higher than that obtained in the control cultures (without alcohol
      or Tween 80), whereas the levels of Lip activity detected were very low (about 12
      u/L)in all the cultures. In further experiments using three kinds of azo dyes of
      congo red, orange G and orange IV, enzyme activities and dye decolorization were
      investigated in the above-mentioned cultures. The results showed that Mnp
      activities and decolorization were notably higher than those obtained in the
      control cultures in the presence of azo dyes. Cultures supplemented with Tween 80
      were more adequate for dye decolorization. The rates of the decolorization with
      Tween 80 of congo red (95.4%), orange G (98.5%) and orange IV (54.4%) after 24
      hours of dye incubation were higher than that supplemented with veratryl alcohol.
      According to the results, Mnp activities secreted by basidiomycete PM2 play an
      essential role in the process of dye decolorization. Tween 80 was the main factor
      affecting the decolorization. The analysis of structure of the three kinds of azo
      dyes indicats that the extent of decolorization is affected by the dye molecular
      structure. The types and quantity of the substituted groups on the aromatic ring
      of azo dyes have effect on the percentage of biological decolorization.

PMID- 15969129
TI  - [Extraction and HPLC analysis of alkaloids in goldenseal].
AB  - An ambient extraction of goldenseal root powder followed by HPLC analysis of the
      alkaloids on a Zorbax Rapid Resolution Eclipse XDB-C18 column provides an
      accurate method for the determination of key alkaloids in goldenseal, including
      berberine and hydrastine. The extraction and HPLC analysis can be applied to
      several other alkaloids, including canadine, hydrastinine, and palmatine, and may
      be applicable to other berberine-containing plant roots. The Rapid Resolution
      Eclipse XDB-C18 column is used for an isocratic separation with high resolution
      of all componentsin under 15 minutes.

PMID- 15969130
TI  - Molecular dynamics study of temperature dehydration of a C12E6 spherical micelle.
AB  - Hydration of a spherical micelles of C12E6 in solution is studied by molecular
      dynamics simulation. The interface is found to be separated in an inner part
      composed of water and hydrophobic and hydrophilic moieties and an outer part with
      hydrophilic moiety and water only. Hydration numbers in the inner and in the
      outer parts are in excellent agreement with experimental data from various
      different methods. Temperature dehydration occurs in the inner region only and is
      related to the presence of water molecules directly in contact with the
      hydrophobic core at low temperature.

PMID- 15969131
TI  - Templated crystallization of octadecanol on patterned nanoassemblies.
AB  - A serial templating methodology using linked aminosilane/stannane units and
      simple beaker chemistry yields thin film nanoassemblies on semiconductor surfaces
      that provide nucleating sites for crystallization of octadecanol, the
      morphologies of which could be tailored using subtle variations in the backbone
      structure of bridged aminosilane/stannanes.

PMID- 15969132
TI  - Eroded myelin figures.
AB  - Myelin figures with unusual surface morphology were observed on contacting
      Tween85 with water. Myelins, which are normally smooth rodlike forms in other
      surfactants, are in this system found to be with an irregular, rough surface with
      vesiclelike structures adhered to the myelin tubes. Besides these, smooth myelin
      figures were also observed. We term the myelin figures with a rough surface
      eroded myelin figures. The same myelin could show a coexistence of smooth and
      rough areas with a sharp boundary between the smooth surface at one end whereas
      the other end shows a rough texture. The transformation of smooth myelins into
      eroded forms were observed often whereas the reverse is quite rare. In the later
      stage, the tip of the eroded myelin figures transforms into tentacles and acts as
      a source for new myelins and the growth of vesiclelike structures which were
      expelled into the surrounding medium. The eroded myelin figures are stable for a
      longer period in comparison to simple, smooth rodlike forms. By studying the
      myelin growth at different temperatures, it was found that eroded myelin figures
      were stable in the temperature range of 22-42 degrees C and at > 42 degrees C
      only smooth myelin figures were observed.

PMID- 15969133
TI  - Synthesis and manipulation of high aspect ratio gold nanorods grown directly on
      surfaces.
AB  - Here we describe the synthesis of Au nanorods directly on glass surfaces using
      seed-mediated deposition of Au from AuCl4- onto surface-attached 3-5 nm diameter
      Au nanoparticles (AuNPs) in the presence of cetyltrimethylammonium bromide
      (CTAB). The average length (200 nm to 1.2 microm) and aspect ratio (6-22) of the
      nanorods increases with increasing AuCl4- concentration. Short, low aspect ratio
      Au nanorods are manipulated with an atomic force microscopy (AFM) tip, while
      longer, high aspect ratio nanorods are bent and broken with the AFM tip.

PMID- 15969134
TI  - Formation of the dimer radical cation of aromatic sulfide on the TiO2 surface
      during photocatalytic reactions.
AB  - The formation of the dimer radical cation (D*+) of 4-(methylthio) benzoic acid on
      a TiO2 surface is demonstrated using the time-resolved diffuse reflectance
      technique. The observed time-resolved diffuse reflectance spectral shape
      significantly depends on the substrate concentrations. The substrate
      concentration dependences of the initial transient signal intensity (%abs.(t=0))
      and the amount of adsorbates (n(ad)) clearly suggest that the formation of D*+ is
      attributableto the high local substrate concentration on the TiO2 surface. The
      electronic influence of substituents on the formation of D*+ is also discussed.

PMID- 15969135
TI  - PNIPAM-co-polystyrene core-shell microgels: structure, swelling behavior, and
      crystallization.
AB  - The present contribution presents the single-step preparation and
      characterization of poly(N-isopropyl acrylamide)-co-polystyrene core-shell
      microgels with varying polystyrene content. The swelling behavior of the
      particles is investigated using dynamic light scattering and differs
      significantly from the swelling behavior of poly(N-isopropyl acrylamide)
      homopolymer particles. The lower critical solution temperature is found to be
      shifted to lower temperatures upon increasing the polystyrene content of the
      particles. The core-shell structure of the particles is revealed by means of
      small angle neutron scattering (SANS) using the method of contrast variation.
      Additionally, the formation of mesoscopic crystals of these particles is
      investigated by means of scanning electron microscopy and also by SANS. The
      particles seem to have preferable properties with respect to crystallization
      compared to homopolymer microgels.

PMID- 15969136
TI  - Stability of various silicone oil/water emulsion films as a function of
      surfactant and salt concentration.
AB  - There have been reports, originally by the Bristol group, and subsequently by
      others, of the preparation and properties of emulsions of stable, nearly
      monodisperse droplets of poly(dimethylsiloxane) (PDMS) in water, where no added
      surfactant is used. It has been assumed that their stability is due to the high
      density of surface-ionized hydroxyl groups, similar in fact to the closely
      related Stober silica particles. In this study we confirm, from droplet lifetime
      studies, that droplets, prepared from such synthesized PDMS, are significantly
      more stable to coalescence than similar-sized droplets prepared from three types
      of commercially available PDMS, containing HO-, MeO-, or Me3-terminated chains,
      respectively. It is shown, however, that the zeta potentials of the synthesized
      PDMS and of the various commercial oils are all very similar (as indeed are their
      Hamaker constants). So some other explanation must be inferred for the enhanced
      stability to coalescence of the synthesized PDMS droplets compared to the
      commercial PDMS droplets. It is shown, for droplets formed from n-hexane and the
      synthesized oil, that stability to coalescence is conferred at PDMS volume
      fractions (phiPDMS) around 0.2 in the mixture. The synthesized PDMS is known to
      consist of mixtures of cyclic PDMS and short-chain linear species, with terminal 
      OH groups. There is some (indirect) evidence that in the interval 0.25 < phiPDMS
      < 0.35, the linear PDMS chains may be adsorbed close to a monolayer at the mixed
      oil/water interface, possibly conferring some enhanced Gibbs elasticity to the
      interface. This underpins the possibility that, in the synthesized oil droplets
      themselves, there is also preferential adsorption of the linear chains at the
      PDMS/water interface, and this leads to a value of the Gibbs elasticity,
      sufficient to significantly reduce coalescence. Unfortunately, the Gibbs
      elasticity could not be measured in this case. However, such preferential
      adsorption is unlikely to occur with the commercial PDMS oils, which are not so
      heterogeneous. Finally, it is shown that droplets of the three commercial PDMS
      oils could be stabilized against coalescence, if a sufficient, minimum amount of
      sodium dodecyl sulfate (SDS) is added. Gibbs elasticity values have been
      estimated in these cases, from plots of interfacial tension against ln(SDS
      concentration).

PMID- 15969137
TI  - Synthesis of sterically stabilized polystyrene latex particles using cationic
      block copolymers and macromonomers and their application as stimulus-responsive
      particulate emulsifiers for oil-in-water emulsions.
AB  - 2-(Dimethylamino)ethyl methacrylate (DMA) was block copolymerized with methyl
      methacrylate (MMA) using group transfer polymerization to give four AB diblock,
      ABA triblock, and BAB triblock copolymers of low polydispersity (Mw/Mn < 1.20).
      In addition, a near-monodisperse styrene-functionalized DMA-based macromonomer
      was synthesized via oxyanionic polymerization using a potassium 4-vinylbenzyl
      alcoholate initiator. These five well-defined, tertiary amine methacrylate-based
      copolymers were evaluated as steric stabilizers for the synthesis of polystyrene
      latexes via emulsion and dispersion polymerization. The most efficient steric
      stabilizers proved to be the DMA-MMA diblock copolymer and the DMA-based
      macromonomer. The polystyrene latexes were characterized in terms of their
      particle size and morphology, stabilizer content, surface charge, and surface
      activity using dynamic light scattering, scanning electron microscopy, 1H NMR
      spectroscopy, aqueous electrophoresis measurements, and surface tensiometry,
      respectively. The pH-dependent surface activity exhibited by selected latexes
      suggests potential applications as stimulus-responsive particulate emulsifiers
      for oil-in-water emulsions.

PMID- 15969138
TI  - Experimental investigation of colloidal gel structures.
AB  - We investigate experimentally the structural properties of colloidal gels, formed
      under both diffusion-limited and reaction-limited aggregation conditions, using
      light scattering measurements and compare the results with the literature Monte
      Carlo (MC) simulations. The scattering structure factors have been measured for
      the two classes of gels in the range of the particle volume fractions between
      0.02 and 0.07. From these, the corresponding fractal dimension values have been
      estimated. These have been found to be in good agreement with those estimated
      from the structure factors computed from MC simulated gels. On the basis of our
      previous research (Lattuada et al. Langmuir 2003, 19, 6312), this confirms that
      the scattering structure factor of a gel provides erroneously a small fractal
      dimension value, which decreases as the particle volume fraction increases.
      Furthermore, it is observed that the average size of the fractal clusters is
      larger in real gels than in simulated gels.

PMID- 15969139
TI  - Structural features of molecular-colloidal solutions of C60 fullerenes in water
      by small-angle neutron scattering.
AB  - Highly stable and reproducible molecular-colloidal water solutions of C60
      fullerenes (FWS) obtained by transferring fullerenes from an organic solution
      into an aqueous phase with the help of ultrasonic treatment are investigated by
      means of small-angle neutron scattering (SANS). A polydispersity in the size of
      detected particles up to 84 nm is revealed. These particles are slightly
      anisotropic and have a characteristic size of approximately 70 nm. Along with it,
      there are some indications that a significant part of fullerenes composes
      particles with the size of the order of 1 nm. The contrast variation based on
      mixtures of light and heavy water shows that the mean scattering length density
      of the particles is close to that of the packed fullerene associates as well as
      that the characteristic size of possible fluctuations of the scattering length
      density within the particles does not exceed 2 nm. A smooth surface resulting in
      the Porod law for the scattering is detected. A number of models discussed in the
      literature are considered with respect to the SANS data.

PMID- 15969140
TI  - Examination of the electrophoretic behavior of liposomes.
AB  - The electromigration of liposomes is a complex process resulting in many
      unexpected behaviors that are difficult to address with existing theories. In
      this study, the electrophoretic behaviors of liposome populations under various
      conditions were examined through the use of capillary electrophoresis and the
      results compared to classical electrokinetic, colloid, and spheroid theories. To
      elucidate the possible effects of applied field strength, bilayer rigidity, and
      surface charge on these behaviors, the electrophoretic mobilities of liposome
      populations were monitored while varying the applied potential, ionic strength of
      the medium, and the surface charge and cholesterol content of the liposomes. On
      the basis of comparisons made to the theoretical predictions, our results suggest
      that liposomal deformation and field-induced polarization may occur during
      electrophoresis and these mechanisms help to describe many of the observed
      behaviors.

PMID- 15969141
TI  - Investigation of the interaction between sodium dodecyl sulfate and cationic
      polymers.
AB  - Aggregation properties of sodium dodecyl sulfate (SDS) on a cationic hydroxyethyl
      cellulose, Polyquaternium-10 (PQ-10), of low charge density were studied by
      potentiometric and pyrene fluorescence methods and compared with those of
      poly(diallyldimethylammomium chloride) (PDADMAC) of high charge density. The
      critical aggregation concentration (cac) was measured with the potentiometric
      method and further confirmed with the fluorescence method. The former was found
      to be more accurate. The value of the cac for the SDS/PQ-10 system was measured
      at 100, 200, and 400 ppm polymer and at 288.2,298.2, and 308.2 K. They showed
      almost the same cac value, 0.04 mmol dm-3. The I1/I3 value of the pyrene
      fluorescence spectrum in the SDS/PQ-10 system at higher SDS concentration was
      smaller than that in SDS/PDADMAC solution and much larger than that of water.
      From the binding isotherm by the potentiometric method, the free DS-
      concentration (Cf) and the bound DS- concentration (Cb) could be evaluated with
      ease over the SDS concentration range above the cac. The aggregation number of DS
      aggregates for both the above polymers was evaluated from the fluorescence
      quenching method using the values of Cf and Cb from the potentiometric method.
      Because Cf in the SDS/PQ-10 system above the cac did not maintain a constant
      value contrary to that in the SDS/PDADMAC system but increased quite a lot, Cb
      should not be regarded as [SDS] - cac above the cac. The aggregation number in
      the SDS/PQ-10 system increased almost linearly with increasing total
      concentration of SDS, while that in the SDS/PDADMAC system reached a plateau.
      With increasing temperature, the aggregation number of the SDS/PDADMAC system
      decreased more rapidly than that of the SDS/PQ-10 system.

PMID- 15969142
TI  - Microstructural characterization of micro- and nanoparticles formed by polymer
      surfactant interactions.
AB  - We have studied the nano- and microparticles formed by complexation of PDAC
      [poly(diallyldimethyl-ammoniumchloride)] and SDS (sodium dodecyl sulfate). The
      complexation phenomenon was characterized by light scattering and zeta-potential
      measurements. The nature of the complexes was revealed by direct-imaging
      cryogenic temperature transmission electron microscopy (cryo-TEM), showing
      nanometric details of the complexes formed around the point of neutralization.
      The images also reveal how those aggregates are solubilized by excess surfactant,
      first into faceted particles with threadlike micelles attached to their surfaces,
      prior to complete solubilization, then into lacelike aggregates, and finally into
      spheroidal micelles. The nanostructure of the complexes strongly suggests they
      are made of a hexagonal liquid crystalline phase. This was further supported by
      small-angle X-ray scattering (SAXS).

PMID- 15969143
TI  - Water-in-CO2 emulsions: reaction vessels for the production of tetra-ethyl
      pyrone.
AB  - Water-in-CO2 (W/C) emulsions formed using a nickel Triton X-100 surfactant
      complex (Ni-surfactant) were used as microreactors for the carbon-carbon coupling
      reaction between hex-3-yne and CO2 to produce tetra-ethyl pyrone (TEP). The
      structure of the product, which was isolated in the CO2 phase, was determined
      using gas chromatography mass spectrometry (GC-MS) and infrared spectroscopy. The
      Ni-surfactant acted as both an emulsion forming agent and a water soluble
      catalyst for this carbon-carbon coupling reaction. The optimum yield of TEP was
      determined to be 69% after 72 h, at a temperature of 70 degrees C and a pressure
      of 206 bar. The ease with which the emulsion could be collapsed allowed the
      facile separation of products from the catalyst and any unreacted starting
      material. Product selectivity in the W/C emulsions was found to be greater than
      that obtained using conventional organic methodologies.

PMID- 15969144
TI  - Freeze fracture direct imaging: a new freeze fracture method for specimen
      preparation in cryo-transmission electron microscopy.
AB  - In this paper, we present a new freeze fracture method for specimen preparation
      for transmission electron microscopy frozen samples. We call it freeze fracture
      direct imaging (FFDI) because it is a hybrid of conventional freeze fracture
      electron microscopy (FFEM) and cryo-transmission electron microscopy (cryo-TEM),
      combining elements of the fracture technique with direct imaging. Like in FFEM,
      the sandwich method is used to prepare the sample in a protected fashion.
      However, after the sample is vitrified and fractured, it is not shadowed but
      directly imaged. The new technique avoids some experimental artifacts produced by
      the blotting procedure in conventional cryo-TEM. It relies, though, on occasional
      fractures transparent to the electrons. The advantageous features are
      demonstrated by a comparison between conventional cryo-TEM and FFDI micrographs
      of vesicular solutions. The second outstanding advantage over conventional cryo
      TEM is the fact that it is now possible for the very first time to directly image
      oil-rich mixtures films which normally would dissolve in the cryo-medium ethane.
      Micrographs of pure oil and of oil-rich microemulsions clearly prove the
      reliability of the FFDI technique as well as its enormous potential.

PMID- 15969145
TI  - Molecular-scale observation of formation of nuclei in soap-free polymerization of
      styrene.
AB  - To clarify the mechanism of the nucleation process in the soap-free
      polymerization of styrene in water, the polymerization process of styrene mainly
      at a temperature 46 degrees C was investigated on a molecular scale using an
      atomic force microscope (AFM) as well as a scanning electron microscope (SEM) and
      a dynamic light scattering apparatus (DLS). A cationic initiator was employed to
      make polymerized styrene adsorb electrostatically on the negatively charged mica
      plate with molecular-scale smoothness, and the mechanism was estimated from their
      AFM measurements in situ in water. The following was found. There exist two
      streams to produce PSL particles in the polymerization: one is the polymerization
      in monomer droplets fragmented by mixing from the main monomer reservoir floating
      above the solution, and the other is the polymerization of monomers dissolved in
      the solution by initiators. The former is normally neglected or not recognized
      because of the small contribution. The latter is the main production process of
      PSL particle, which is investigated in detail on a molecular scale, and a
      possible mechanism was proposed.

PMID- 15969146
TI  - Low-temperature mobility and structure formation of a prochiral aromatic thiol
      (2,5-dichlorothiophenol) on Cu(111).
AB  - We present a low-temperature scanning tunneling microscopy study of increasing
      coverages of 2,5-dichlorothiophenol, an asymmetrically halo-substituted aromatic
      thiol, on Cu(111). At low coverage, deprotonation of the thiol occurs
      spontaneously upon adsorption at 80 K. Albeit the low deposition temperature, we
      find the formation of adsorbate islands at low coverage, which coalesce into a
      well-ordered film of horizontally adsorbed molecules at increasing coverage. This
      behavior indicates (i) significant mobility of the thiols on Cu(111) even at low
      temperatures and (ii) attractive adsorbate-adsorbate interactions. At higher
      coverages intermolecular interactions prevent long-range diffusion of adsorbates
      and thermal activation of the S-H bond becomes necessary. A close analysis of the
      molecular films reveals chiral recognition between neighboring molecules, which
      leads to the formation of enantiopure areas on the surface. Upright orientation
      of individual molecules starts at the boundaries between such phases and can be
      induced by scanning tunneling microscopy.

PMID- 15969147
TI  - Scanning tunneling microscopy study of the structure and orbital-mediated
      tunneling spectra of cobalt(II) phthalocyanine and cobalt(II)
      tetraphenylporphyrin on au(111): mixed composition films.
AB  - Binary thin films of cobalt(II) phthalocyanine (CoPc) and cobalt(II)
      tetraphenylporphyrin (CoTPP) were prepared at submonolayer coverage on
      Au(111)/mica substrates byvapor deposition. All sample preparation and analysis
      were done under an ultrahigh vacuum. Scanning tunneling microscopy (STM) constant
      current images of CoPc/CoTPP mixtures showed two close-packed surface structures,
      with different compositional percentages and some disorder. CoPc was also
      observed exclusively in one-dimensional chains and as single, isolated molecules
      below 220 K. Occupied and unoccupied orbital energy levels were identified by STM
      and tunnel-diode-based orbital-mediated tunneling spectroscopy. Occupied energy
      levels were also confirmed by ultraviolet photoelectron spectroscopy. The
      transient oxidation of the Co d(z2) orbital is identified in STM dI/dV(V) curves
      just negative of the 0 V sample bias for both molecules. Nearly identical
      constant-current contours are observed over the central Co2+ ions of CoTPP and
      CoPc, indicating that the attenuation of the d(z)2 orbital-mediated tunneling
      current induced by the structure of TPP relative to Pc is at most a factor of
      about 10. The orbital-mediated tunneling spectra of CoTPP and CoPc are distinctly
      different and allow these structurally similar species to be differentially
      identified.

PMID- 15969148
TI  - Walljet electrochemistry: quantifying molecular transport through
      metallopolymeric and zirconium phosphonate assembled porphyrin square thin films.
AB  - By employing redox-active probes, condensed-phase molecular transport through
      nanoporous thin films can often be measured electrochemically. Certain kinds of
      electrode materials (e.g. conductive glass) are difficult to fabricate as
      rotatable disks or as ultramicroelectrodes-the configurations most often used for
      electrochemical permeation measurements. These limitations point to the need for
      a more materials-general measurement method. Herein, we report the application of
      walljet electrochemistry to the study of molecular transport through model
      metallopolymeric films on indium tin oxide electrodes. A quantitative expression
      is presented that describes the transport-limited current at the walljet
      electrode in terms of mass transport through solution and permeation through the
      film phase. A comparison of the film permeabilities for a series of redox probes
      measured using the walljet electrode and a rotating disk electrode establishes
      the accuracy of the walljet method, while also demonstrating similar precision
      for the two methods. We apply this technique to a system consisting of zirconium
      phosphonate assembled films of a porphyrinic molecular square. Transport through
      films comprising three or more layers is free from significant contributions from
      pinhole defects. Surprisingly, transport through films of this kind is 2-3 orders
      of magnitude slower than through films constructed via interfacial polymerization
      of nearly identical supramolecular square building blocks (Keefe; et al. Adv.
      Mater. 2003, 15, 1936). The zirconium phosphate assembled films show good size
      exclusion behavior. The details of the observed dependence of permeation rates on
      probe molecule size can be rationalized with a model that assumes that the walls
      of the squares are slightly tilted from a strictly vertical geometry, consistent
      with atomic force microscopy measurements, and assumes that the individual wall
      geometries are locked by rigid interlayer linkages.

PMID- 15969149
TI  - Controlled nanoparticle assembly by dewetting of charged polymer solutions.
AB  - In this paper, we present an alternative approach for controlled nanoparticle
      organization on a solid substrate by applying dewetting patterns of charged
      polymer solutions as a templating system. Thin films of charged polymer solutions
      dewet a solid substrate to form complex dewetting patterns that depend on the
      polymer charge density. These patterns, ranging from polygonal networks to
      elongated structures that are stabilized by viscous forces during dewetting,
      serve as potential templates for two-dimensional nanoparticle organization on a
      solid substrate. Thus, while nanoparticles dried in pure water undergo self
      assembly to form close-packed arrays, addition of charged polymer in the
      dispersion leads to the formation of open structures that are directed by the
      dewetting patterns of the polymer solution. In this study, we focus on the
      application of elongated structures resulting from dewetting of high-charge
      density polymer solutions to align nanoparticles of silica and gold into long
      chains that are several micrometers in length. The particle ordering process is a
      two-step mechanism: an initial confinement of the nanoparticles in the dewetting
      structures and self-assembly of the particles within these structures upon
      further drying by lateral capillary attractions.

PMID- 15969150
TI  - Adsorption of ionic surfactants at an expanding air-water interface.
AB  - A quantitative model for the kinetics of adsorption of ionic surfactants to an
      expanding liquid surface is presented for surfactant concentrations below and
      above the critical micelle concentration (cmc). For surfactant concentrations
      below the cmc, the electrostatic double layer is accounted for explicitly in the
      adsorption isotherm. An overflowing cylinder (OFC) was used to create
      nonequilibrium liquid surfaces under steady-state conditions. Experimental
      measurements of the surface excess for solutions of cationic surfactants
      CH3(CH2)n-1N+(CH3)3 Br- (CnTAB, n = 12, 14, 16) and the anionic fluorocarbon
      surfactant sodium bis(1H,1H-nonafluoropentyl)-2-sulfosuccinate (di-CF4) in the
      OFC are in excellent agreement with the theoretical predictions for diffusion
      controlled adsorption for all concentrations studied below the cmc. For
      surfactant concentrations above cmc, the diffusion ofmicelles and monomers are
      handled separately under the assumption of fast micellar breakdown. This
      simplified model gives excellent agreement for the system C14TAB + 0.1 M NaBr
      above the cmc. Agreement between theory and experiment for C16TAB + 0.1 M NaBr is
      less good. A plausible explanation for the discrepancy is that micellar breakdown
      is no longer fast on the time scale of the OFC (ca. 0.1 s).

PMID- 15969151
TI  - Experimental observations on the scaling of adsorption isotherms for nonionic
      surfactants at a hydrophobic solid-water interface.
AB  - The self-assembly of nonionic surfactants in bulk solution and on hydrophobic
      surfaces is driven by the same intermolecular interactions, yet their
      relationship is not clear. While there are abundant experimental and theoretical
      studies for self-assembly in bulk solution and at the air-water interface, there
      are only few systematic studies for hydrophobic solid-water interfaces. In this
      work, we have used optical reflectometry to measure adsorption isotherms of seven
      different nonionic alkyl polyethoxylate surfactants (CH3(CH2)I-1(OCH2CH2)JOH,
      referred to as CIEJ surfactants, with I = 10-14 and J = 3-8), on hydrophobic,
      chemically homogeneous self-assembled monolayers of octadecyltrichlorosilane.
      Systematic changes in the adsorption isotherms are observed for variations in the
      surfactant molecular structure. The maximum surface excess concentration
      decreases (and minimum area/molecule increases) with the square root of the
      number of ethoxylate units in the surfactant (J). The adsorption isotherms of all
      surfactants collapse onto the same curve when the bulk and surface excess
      concentrations are rescaled by the bulk critical aggregation concentration (CAC)
      and the maximum surface excess concentration. In an accompanying paper we compare
      these experimental results with the predictions of a unified model developed for
      self-assembly of nonionic surfactants in bulk solution and on interfaces.

PMID- 15969152
TI  - Unified model to predict self-assembly of nonionic surfactants in solution and
      adsorption on solid or fluid hydrophobic surfaces: effect of molecular structure.
AB  - We have developed a pseudo-phase model to predict the self-assembly of nonionic
      surfactants on hydrophobic solid or fluid interfaces and in bulk solution. The
      uniqueness of this model is that it provides the relationship between molecular
      structure and self-assembly in solution and on interfaces. This model requires
      the input of minimal new experimental data. The remaining model parameters may be
      calculated on the basis of the surfactant molecular structure. The validity of
      the model has been established by comparing predictions with a wide array of
      experimental data for nonionic surfactant adsorption at the hydrophobic solid
      water interface and at the air-water interface. The same model is then used to
      predict the self-assembly in bulk solution. The model predictions for critical
      aggregation concentration, aggregate shapes, and adsorption isotherms of various
      surfactants are in good agreement with the experimental data available in the
      literature.

PMID- 15969153
TI  - Solvent vapor mediated polymer adsorption in thin films.
AB  - The effectiveness of a "solvent annealing" process was investigated for thin
      (approximately 150 nm) polystyrene films, in which the diffusion and
      reorganization of polymer chains were mediated by the controlled absorption of
      cyclohexane vapor. Results were compared with conventional "thermal annealing" of
      films under vacuum above the glass transition temperature. Elastic recoil
      detection analysis (ERDA) was used to determine the surface excesses of
      fluorocarbon end-capped polystyrene (hPSF) and poly(styrene-b-dimethylsiloxane)
      (hPS-PDMS) in deuterated polystyrene (dPS) films. Both annealing methods enabled
      diffusion of the surface-active polymers; however, only thermal annealing gave
      rise to a surface excess in hPSF/dPS films. The inhibition ofhPSF adsorption
      under solvent annealing was due to the low surface tension of cyclohexane. In
      contrast, hPS-PDMS, having a larger surface-active group than that of hPSF, was
      found in excess at the air surface under solvent annealing, and surface excesses
      were consistent with the formation of saturated monolayers in blended films. The
      mixing of hPS-PDMS with dPS was inhibited by the unfavorable interaction between
      the PDMS block of the copolymer and the homopolymer. The slow interdiffusion of
      hPS-PDMS in dPS is consistent with the formation of micelles, and the formation
      of an excess layer at the air surface may be kinetically inhibited by the rate of
      dissociation of hPS-PDMS micelles.

PMID- 15969154
TI  - Electroactive self-assembled biferrocenyl alkanethiol monolayers on Au(111)
      surface and on gold nanoclusters.
AB  - The spectroscopic and electrochemical characterizations of electrochemically
      stable biferrocene-modified Au clusters and chemisorbed biferrocenylalkanethiols
      on Au(111) surface were studied. The characterizations of biferrocene-modified Au
      cluster using TEM, UV-vis, and NMR techniques are also reported. Two successive
      reversible one-electron redox waves were observed for the biferrocenylalkanethiol
      Au nanoclusters and biferrocenylalkanethiol monolayers on Au(111) surface in the
      cyclic voltammetry. Furthermore, the positive and negative current peaks for each
      redox wave occur at almost the same potential, and the peak current increases
      almost linearly with the sweep rate. Repeat scanning does not change the
      voltammograms, demonstrating that these monolayers are stable to electrochemical
      cycling. The coverages of electroactive biferrocene in the monolayers were
      calculated from the cyclic voltammograms. The standard electron-transfer rate
      constant was calculated from the splitting between the oxidation and reduction
      peaks.

PMID- 15969155
TI  - Detailed modeling of the volume fraction profile of adsorbed polymer layers using
      small-angle neutron scattering.
AB  - A detailed analysis of on and off-contrast small-angle neutron scattering from
      poly(ethylene oxide)s adsorbed on polystyrene latex is presented. The results
      have been fitted to an exponential decay, self-consistent mean-field (SCF) and
      scaling models of the volume fraction profile. As the chain length increases a
      clear self-similar layer emerges in both the SCF and scaling profiles. The RMS
      thickness of the adsorbed layer in the plateau of the adsorption isotherm varies
      as M0.4 for both the SCF and scaling profiles but the exponential one however
      gives a much lower exponent consistent with the neglect of the tail or distal
      region. The new constrained version of the Scheutjens-Fleer model was able to
      predict the structure of the layer and hence the scattering with great accuracy.

PMID- 15969156
TI  - Heats of adsorption using temperature programmed adsorption equilibrium:
      application to the adsorption of CO on Cu/A12O3 and H2 on Pt/Al2O3.
AB  - A new simple analytical procedure is described that allows the determination of
      the heats of adsorption (denoted E(theta)) of adsorbed species at several
      coverages (theta's) using a single experiment. This procedure is an extension of
      an original method previously developed (denoted AEIR: adsorption equilibrium
      infrared spectroscopy). A mass spectrometer is used to determine the amounts of
      gas (in the present study, CO and H2) either desorbed from or adsorbed on a metal
      supported catalyst (4.7% Cu/Al2O3 and 2.9% Pt/Al2O3) during the perturbation of
      the adsorption equilibrium due to a controlled change of the adsorption
      temperature (Ta) at a quasi-constant adsorption pressure (Pa). These amounts
      allow us to follow the evolution of the adsorption equilibrium coverage
      (theta(e)) with Ta at the quasi-constant partial pressure (Pa). Then, the curve
      theta(e) = f(Ta) provides Etheta = f(theta) with the support of an adsorption
      model. This procedure presents several advantages as compared to the TPD methods,
      in particular, considering the theoretical supports linked to the exploitation of
      the experimental data. As compared to AEIR, the TPAE procedure allows one to
      study the heats of adsorption of adsorbed species that are not detectable by IR.
      However, it is not adapted if surface reactions occur in parallel to
      adsorption/desorption processes.

PMID- 15969157
TI  - Binding of Cd2+ to self-assembled bilayers bearing pyridine terminal groups:
      attenuated total reflection Fourier transform infrared spectroscopic studies.
AB  - Various aspects of the adsorption of Cd2+ on self-assembled monolayers (SAMs) of
      4-heptadecylpyridine (HDpy) and 7-tridecyl-4-methyl-1,10-bipyridine (TMbipy)
      supported on an octadecylsilane (ODS)-modified Ge prism have been examined both
      ex situ (dry) and in situ (in the presence of aqueous solutions) using attenuated
      total reflection Fourier transform infrared spectroscopy. In direct analogy with
      the behavior found for a variety of genuine pyridine (py) and bipyridine (bipy)
      metal ion complexes, Cd2+ binding to both SAMs led to shifts in the skeletal
      vibrational modes of the corresponding uncoordinated ligands in the region 1650
      1400 cm(-1), toward higher energies. Analysis of spectra acquired ex situ for
      HDpy/ODS/Ge and TMbipy/ODS/Ge before and after exposure to 0.1 mM [Cd2+] yielded
      values for the fraction of uncoordinated py, theta(py(un)), and uncoordinated
      bipy, theta(bipy(un)), of about 0.5 and about 0.1, respectively. The features
      attributed to the py(un) groups for spectra collected for HDpy/ODS/Ge in situ and
      ex situ were found to be virtually identical, making it possible to isolate by
      graphical means the most prominent band of py(co) centered at about 1615 cm(-l)
      for HDpy/ODS/Ge collected in situ. The resulting bands for pure py(co) and pyun
      in situ were then used to deconvolute spectra recorded in situ for HPpy/ODS/Ge in
      contact with Cd2+containing solutions in the range 10 nM < [Cd2+] < 0.1 mM, from
      which information regarding the adsorption isotherm was obtained.

PMID- 15969158
TI  - Nature of adsorption and desorption branches in cylindrical pores.
AB  - To examine the nature of the adsorption and desorption branches in hysteretic
      adsorption isotherms of gases on mesoporous materials, we measured the
      temperature dependence of the adsorption and desorption isotherms of argon,
      oxygen, and carbon dioxide onto MCM-41 with a pore diameter of 4.4 nm. The
      results clearly show that in the open-ended cylindrical pores of MCM-41,
      capillary condensation rather than evaporation takes place near a thermodynamical
      equilibrium transition, as opposed to the general statement that capillary
      evaporation can occur via a meniscus formed at the pore mouth, and, thus, takes
      place at equilibrium.

PMID- 15969159
TI  - Infrared study of the kinetics and mechanism of adsorption of acrylic polymers on
      alumina surfaces.
AB  - In this paper, we studied the kinetics of the adsorption of poly(methyl
      methacrylate), PMMA, onto native aluminum oxide surfaces by X-ray photoelectron
      spectroscopy and reflection-absorption infrared spectroscopy, with the intent of
      tracking the various changes observed in the infrared spectrum of the adsorbed
      polymer layer as a function of adsorption time. Specifically, we utilized the
      relative changes in the absorption bands of the carbonyl, carboxylic acid, and
      carboxylate groups to determine the sequence of events that culminate in the
      formation of bonds between carboxylate groups on hydrolyzed PMMA and specific
      sites on the aluminum oxide surface. We have shown that the adsorption process
      involves the hydrolysis of a fraction of the methoxy groups of the PMMA to
      generate COOH groups. Unlike previous assumptions, the formation of COOH groups
      on the PMMA chains does not constitute a sufficient condition for the actual
      chemisorption of the polymer chains onto the metal oxide surface. To promote
      bonding, the acid groups must undergo dissociation to form the carboxylate
      groups, followed subsequently by actual bond formation, that is, active
      anchoring, on the surface. This process is mediated by the aluminum oxide sites
      on the surface in the presence of water. Hence, the adsorption process occurs via
      a two-step mechanism, in which the first step, that is, the hydrolysis step, is a
      necessary but insufficient condition and the second step, that is, the anchoring
      step, is largely dependent on the type of interfacial chemistry possible for a
      particular polymer-metal oxide surface, the polymer conformation, the molecular
      weight, and the flexibility of the adsorbing molecules.

PMID- 15969160
TI  - Structural and topographical characteristics of adsorbed WPI and monoglyceride
      mixed monolayers at the air-water interface.
AB  - In this work we have analyzed the structural and topographical characteristics of
      mixed monolayers formed by an adsorbed whey protein isolate (WPI) and a spread
      monoglyceride monolayer (monopalmitin or monoolein) on the previously adsorbed
      protein film. Measurements of the surface pressure (pi)-area (A) isotherm were
      obtained at 20 degrees C and at pH 7 for protein-adsorbed films from water in a
      Wilhelmy-type film balance. Since the surface concentration (1/A) is actually
      unknown for the adsorbed monolayer, the values were derived by assuming that the
      A values for adsorbed and spread monolayers were equal at the collapse point of
      the mixed film. The pi-A isotherm deduced for adsorbed WPI monolayer in this work
      is practically the same as that obtained directly by spreading. For WPI
      monoglyceride mixed films, the pi-A isotherms for adsorbed and spread monolayers
      at pi higher than the equilibrium surface pressure of WPI are practically
      coincident, a phenomenon which may be attributed to the protein displacement by
      the monoglyceride from the interface. At lower surface pressures, WPI and
      monoglyceride coexist at the interface and the adsorbed and spread pi-A isotherms
      (i.e., the monolayer structure of the mixed films) are different. Monopalmitin
      has a higher capacity than monoolein for the displacement of protein from the air
      water interface. However, some degree of interactions exists between proteins and
      monoglycerides and these interactions are higher for adsorbed than for spread
      films. The topography of the monolayer corroborates these conclusions.

PMID- 15969161
TI  - Sliding friction at a rubber/brush interface.
AB  - We study the friction of a poly(dimethylsiloxane) (PDMS) rubber network sliding,
      at low velocity, on a substrate on which PDMS chains are end-tethered. We thus
      clearly evidence the contribution to friction of the pullout mechanism of chain
      ends that penetrate into the network. This interfacial dissipative process is
      systematically investigated by probing the velocity dependence of the friction
      stress and its variations with the grafting density and molecular weight of the
      tethered chains. This allows us to confirm semiquantitatively the picture of arm
      retraction relaxation of the grafted chains proposed in models of slippage at a
      network/brush interface.

PMID- 15969162
TI  - Structural, topographical, and shear characteristics of milk protein and
      monoglyceride monolayers spread at the air-water interface.
AB  - In this contribution we are concerned with the study of structure, topography,
      and surface rheological characteristics under shear conditions of monoglyceride
      (monopalmitin and monoolein) and milk protein (beta-casein, kappa-casein,
      caseinate, and WPI) spread monolayers at the air-water interface. Combined
      surface chemistry (surface film balance and surface shear rheometry) and
      microscopy (Brewster angle microscopy: BAM) techniques have been applied in this
      study to pure emulsifiers (proteins and monoglycerides) spread at the air-water
      interface. To study the shear characteristics of spread films, a homemade canal
      viscometer was used. The experiments have demonstrated the sensitivity of the
      surface shear viscosity (eta(s)) of protein and monoglyceride films at the air
      water interface, as a function of surface pressure (or surface density). The
      surface shear viscosity was higher for proteins than for monoglycerides. In
      addition, eta(s) was higher for the globular WPI than for disordered beta-casein
      and caseinate due to the strong forces acting on spread globular proteins. This
      technique makes it possible to distinguish between beta-casein and caseinate
      spread films, with the higher eta(s) values for the later due to the presence of
      kappa-casein. The eta(s) value varies greatly with the surface pressure (or
      surface density). In general, the greater the surface pressure, the greater the
      values of eta(s). Finally, the eta(s) value is also sensitive to the monolayer
      structure, as was observed for monoglycerides with a rich structural polymorphism
      (i.e., monopalmitin).

PMID- 15969163
TI  - Polypeptide multilayer films: role of molecular structure and charge.
AB  - The role of molecular structure, charge, and hydrophobicity in polyelectrolyte
      layer-by-layer assembly (LbL) of thin films has been studied using the model
      polypeptides poly-L-glutamatic acid (PLGA) and poly-L-lysine (PLL), quartz
      crystal microbalance (QCM), and circular dichroism spectroscopy (CD). The
      adsorption behavior of PLGA and PLL has been compared with the structure of these
      molecules in aqueous solution under the same conditions. The data show that the
      deposition of polypeptide per adsorption step scales with average secondary
      structure content, whether alpha helix or beta sheet. This is contrary to the
      expectation based on the view that hydrogen bonds are crucial to polypeptide film
      assembly, because secondary structure formation in a polypeptide reduces its
      intermolecular hydrogen-bonding potential. The data also show that polypeptide
      adsorption scales with ionic strength and chain length. Taken together, the
      results increase knowledge of polypeptide-based LbL thin film fabrication and
      will help to provide a firmer foundation for the use of natural or designed
      polypeptides in LbL.

PMID- 15969164
TI  - Effect of trace amounts of water on organic solvent transport through gamma
      alumina membranes with varying pore sizes.
AB  - The transport behavior of toluene and n-hexane in gamma-alumina membranes with
      different pore diameters was studied. It was shown that the permeability of water
      lean hexane and toluene is in agreement with Darcy's law down to membrane pore
      diameters of 3.5 nm. The presence of molar water fractions of 5-8 x 10(-4) in
      these solvents led to a permeability decrease of the gamma-alumina layer by a
      factor of 2-4 depending on pore size. In general, a lower permeability was found
      for hexane than for toluene. Moreover, in the presence of water a minimum applied
      pressure of 0.5-1.5 bar was required to induce net liquid flow through the
      membrane. These phenomena were interpreted in terms of capillary condensation of
      water in membrane pores with a size below a certain critical diameter. This is
      thought to lead to substantial blocking of these pores for transport, so that the
      effective tortuosity of the membrane for transport of hydrophobic solvents
      increases.

PMID- 15969165
TI  - Forces between glass surfaces in mixed cationic-zwitterionic surfactant systems.
AB  - We report atomic force microscopy (AFM) measurements of the forces between
      borosilicate glass solids in aqueous mixtures of cationic and zwitterionic
      surfactants. These forces are used to determine the adsorption of the surfactant
      as a function of the separation between the interfaces (proximal adsorption)
      through the application of a Maxwell relation. In the absence of cationic
      surfactant, the zwitterionic surfactant N-dodecyl-N,N-dimethyl-3-ammonio-1
      propanesulfonate (DDAPS) undergoes little adsorption to glass at concentrations
      up to about 2/3 critical micelle concentration (cmc). In addition, DDAPS does not
      have much effect on the forces over the same concentration range. In contrast,
      the cationic surfactant dodecylpyridinium chloride (DPC) does adsorb to glass and
      does affect the force between glass surfaces at concentrations much lower than
      the cmc. In the presence of a small amount of DPC (0.05 mM = cmc/300), the net
      force between the glass surfaces is quite sensitive to the solution concentration
      of DDAPS. A model-independent thermodynamic argument is used to show that the
      surface excess of DDAPS depends on the separation between the glass interfaces
      when the cationic surfactant is present and that the surface excess of the
      cationic surfactant is more sensitive to interfacial separation in the presence
      of the zwitterionic surfactant. The change in adsorption of the zwitterionic
      surfactant is explained in terms of an intermolecular coupling between the long
      range electrostatic force acting on the cationic surfactant and the short-range
      hydrophobic interaction between the alkyl chains on the cationic and zwitterionic
      surfactants. The adsorptions of cationic and zwitterionic surfactants in mixtures
      were measured independently and simultaneously by attenuated total internal
      reflection infrared spectroscopy (ATR-IR). The adsorption of the zwitterionic
      surfactant is enhanced by the presence of a small amount of cationic surfactant.

PMID- 15969166
TI  - Thermodynamic characterization of asphaltene-resin interaction by
      microcalorimetry.
AB  - This paper collects the work performed by isothermal titration calorimetry (ITC)
      to characterize the interaction between petroleum asphaltenes and resins. The
      interaction between these two fractions is of great interest in order to
      understand the mechanism of stabilization ofasphaltenes in crude oil. To simplify
      the approach, this preliminary study focuses on toluene solutions of both
      fractions. This paper reports the experimental determination of the average
      number of sites in asphaltene molecules and the enthalpy of interaction between
      asphaltenes and resins. Two models have been used to fit the experimental data.
      The enthalpies calculated by ITC are in the order of -2 to -4 kJ/mol. These
      values are in the limit of hydrogen bonding and permanent dipole energies.
      Similar values have been obtained by using the enthalpy as a fitting parameter in
      the SAFT equation.

PMID- 15969167
TI  - Competitive adsorption of aqueous metal ions on an oxidized nanoporous activated
      carbon.
AB  - Competitive adsorption is the usual situation in real applications, and it is of
      critical importance in determining the overall performance of an adsorbent. In
      this study, the competitive adsorption characteristics of all the combinations of
      binary mixtures of aqueous metal ion species Ca2+(aq), Cd2+(aq), Pb2+(aq), and
      Hg2+(aq) on a functionalized activated carbon were investigated. The porous
      structure of the functionalized active carbon was characterized using N2 (77 K)
      and CO2 (273 K) adsorption. The surface group characteristics were examined by
      temperature-programmed desorption, Fourier transform infrared spectroscopy, Raman
      spectroscopy, acid/base titrations, and measurement of the point of zero charge
      (pHpzc). The adsorption of aqueous metal ion species, M2+(aq), on acidic oxygen
      functional group sites mainly involves an ion exchange mechanism. The ratios of
      protons displaced to the amount of M2+(aq) metal species adsorbed have a linear
      relationship for both single-ion and binary mixtures of these species. Hydrolysis
      of metal species in solution may affect the adsorption, and this is the case for
      adsorption of Hg2+(aq) and Pb2+(aq). Competitive adsorption decreases the amounts
      of individual metal ions adsorbed, but the maximum amounts adsorbed still follow
      the order Hg2+(aq) > Pb2+(aq) > Cd2+(aq) > Ca2+(aq) obtained for single metal ion
      adsorption. The adsorption isotherms for single metal ion species were used to
      develop a model for competitive adsorption in binary mixtures, involving exchange
      of ions in solution with surface proton sites and adsorbed metal ions, with the
      species having different accessibilities to the porous structure. The model was
      validated against the experimental data.

PMID- 15969168
TI  - Layer by layer characterization of 1-octadecanol films on a Au(111) electrode
      surface. "In situ" polarization modulation infrared reflection absorption
      spectroscopy and electrochemical studies.
AB  - Bilayers of 1-octadecanol were transferred from the gas-solution interface onto a
      Au(111) electrode surface using either the horizontal touch or the Langmuir
      Blodgett (LB) technique. The horizontal touch method gives an X-type film in
      which the molecule in the bottom layer is oriented with the tail toward the metal
      and the head toward the tail of the molecule in the top layer (head to tail
      orientation). The LB technique allows one to build not only X but also a Y
      bilayer, in which the molecules in the two leaflets are oriented tail to tail
      with the polar heads facing the metal and the solution. The properties of these
      films were characterized by electrochemistry and polarization modulation infrared
      reflection absorption spectroscopy (PM IRRAS). The freshly prepared X bilayer is
      defect free and is characterized by a low capacity of 0.84 microF cm(-2). The
      bilayer may be desorbed from the electrode surface at E < -0.6 V and readsorbed
      again at more positive potentials. The potential-driven readsorption gives a Y
      film with a higher capacity of 2.2 microF cm(-2). The IR studies of a mixed
      bilayer composed of one hydrogenated leaflet and a second deuterated leaflet
      showed that 1-octadecanol molecules assume a more vertical orientation in the
      leaflet facing the solution than in the leaflet in contact with the metal. Upon
      desorption of the X film, the molecules in the bottom layer flip-flop and the
      readsorbed film assumes the Y structure. Smaller tilt angles are observed in the
      X film as opposed to the Y film.

PMID- 15969169
TI  - Structure and electrochemistry of 4,4'-dithiodipyridine self-assembled monolayers
      in comparison with 4-mercaptopyridine self-assembled monolayers on Au(111).
AB  - 4,4'-Dithiodipyridine (PySSPy) monolayers on Au(111) were investigated by cyclic
      voltammetry, X-ray photoelectron spectroscopy (XPS) and in situ scanning
      tunneling microscopy (STM). The studies were performed in solutions of different
      anions and pHs (0.1 M H2SO4, 0.1 M HClO4, 0.1 and 0.01 M Na2SO4, 0.1 and 0.01 M
      NaOH). The cyclic current-potential curves in H2SO4 show current peaks at about
      0.4 V, which are absent for all other electrolytes at this potential. The XPS
      data suggest that PySSPy adsorbs via the S endgroup on the gold surface and the S
      S bond breaks during adsorption. From the chemical shift of the N(ls) peak, it is
      concluded that in acidic media the self-assembled monolayer (SAM) is fully
      protonated, whereas in basic solution it is not. The pKa is estimated to be 5.3.
      STM studies reveal the existence of highly ordered superstructures for the SAM.
      In Na2SO4 and H2SO4, a (7 x mean square root of 3) structure is proposed.
      However, whereas in Na2SO4 solutions the superstructure does not change with
      potential, in 0.1 M H2SO4 the superstructure is observed only negative of the
      current peak at +0.4 V. At more positive potentials, the film becomes disordered.
      The results are compared to those for 4-mercaptopyridine (PyS) SAMs. XPS
      experiments and current-potential curves indicate that both molecules adsorb in
      the same manner on Au(111), that is, even in the case of PySSPy the adspecies is
      PyS. The STM results, however, call for a more subtle interpretation. While in
      Na2SO4 solutions the observed superstructures are the same for both SAMs,
      markedly different structures are found for PySSPy and PyS SAMs in 0.1 M H2SO4.

PMID- 15969170
TI  - Scanning tunneling microscopy of sulfur and benzenethiol chemisorbed on Ru(0001)
      in 0.1 M HClO4.
AB  - In situ scanning tunneling microscopy (STM) combined with linear sweep
      voltammetry was used to examine spatial structures of sulfur adatoms (SA) and
      benzenethiol (BT) molecules adsorbed on an ordered Ru(0001) electrode in 0.1 M
      HClO4. The Ru(0001) surface, prepared by mechanical polishing and electrochemical
      reduction at -1.5 V (vs RHE) in 0.1 M HClO4, contained atomically flat terraces
      with an average width of 20 nm. Cyclic voltammograms obtained with an as-prepared
      Ru(0001) electrode in 0.1 M HClO4 showed characteristics nearly identical to
      those of Ru(0001) treated in high vacuum. High-quality STM images were obtained
      for SA and BT to determine their spatial structures as a function of potential.
      The structure of the SA adlayer changed from (2 x mean square root of 3)rect to
      domain walls to (mean square root of 7 x mean square root of 7)R19.1 degrees and
      then to disordered as the potential was scanned from 0.3 to 0.6 V. In contrast,
      molecules of BT were arranged in (2 x mean square root of 3)rect between 0.1 and
      0.4 V, while they were disordered at all other potentials. Adsorption of BT
      molecules was predominantly through the sulfur headgroup. Sulfur adatoms and
      adsorbed BT molecules were stable against anodic polarization up to 1.0 V (vs
      RHE). These two species were adsorbed so strongly that their desorption did not
      occur even at the onset potential for the reduction of water in 0.1 M KOH.

PMID- 15969171
TI  - Temperature dependence of formation of nanorods and dots of iodine compounds on
      an H-terminated Si(111) surface in a concentrated HI solution.
AB  - Immersion of atomically flat, H-terminated Si(111) surfaces in 7.6 M HI for 0.5 -
      4 h caused spontaneous formation of nanosized clusters at the Si surface. X-ray
      photoelectron spectroscopy analysis suggested that the clusters were composed of
      silicon iodides (such as SiHxI4-x), produced most probably by Si etching with HI.
      Atomic force microscopy inspection revealed that the immersion at a low
      temperature below about 30 degrees C led to the formation of long rod-shaped
      clusters, oriented in the (112) direction or equivalents, whereas the immersion
      at a high temperature above 30 degrees C led to the formation of circular dot
      clusters, their size and shape changing abruptly at about 70 degrees C. It is
      shown experimentally that the formation of dot clusters at a high immersion
      temperature is explained on the basis of thermodynamics, whereas that of oriented
      rod clusters at a low temperature is explained by a kinetics-controlled
      mechanism.

PMID- 15969172
TI  - QCM-D on mica for parallel QCM-D-AFM studies.
AB  - Quartz crystal microbalance with dissipation monitoring (QCM-D) has developed
      into a recognized method to study adsorption processes in liquid, such as the
      formation of supported lipid bilayers and protein adsorption. However, the large
      intrinsic roughness of currently used gold-coated or silica-coated QCM-D sensors
      limits parallel structural characterization by atomic force microscopy (AFM). We
      present a method for coating QCM-D sensors with thin mica sheets operating in
      liquid with high stability and sensitivity. We define criteria to objectively
      assess the reliability of the QCM-D measurements and demonstrate that the mica
      coated sensors can be used to follow the formation of supported lipid membranes
      and subsequent protein adsorption. This method allows combining QCM-D and AFM
      investigations on identical supports, providing detailed physicochemical and
      structural characterization of model membranes.

PMID- 15969173
TI  - Synthesis, loading, and application of individual nanocapsules for probing single
      cell signaling.
AB  - This paper describes the synthesis and loading of silica and polystyrene-acrylic
      based nanocapsules with small molecules. The nanocapsules are used for delivering
      defined packages of stimuli to single cells with both high spatial and temporal
      resolutions. To introduce molecules into the capsules, we characterized two
      approaches. The first approach is based on a base-swell process in which the
      shell of the capsule is swelled so small molecules can diffuse into the interior
      of the capsule and be trapped inside once the capsules are de-swelled. The second
      approach is based on a dry-swell-dry process in which the solution containing the
      molecules of interest and the nanocapsules is physically dried to promote more
      molecules to enter into the interior of the capsule. We characterized both
      methods by monitoring the content of and the release from individual capsules
      with confocal microscopy and wide-field imaging. To illustrate the biological
      applications of such nanocapsules, we used optical trapping to position a single
      carbachol-loaded capsule adjacent to a single CHO cell that has been transfected
      with muscarinic acetylcholine (M1) receptors, released the carbachol from the
      capsule with a single 3-ns N2 laser pulse, and then monitored the subsequent
      intracellular signaling triggered by the binding of carbachol to the M1
      receptors.

PMID- 15969174
TI  - In situ sensing of salinity in oriented lipid multilayers by surface X-ray
      scattering.
AB  - The influence of LiCl solutions on liposomal and surface-supported
      phosphatidylcholine/water systems (dipalmitoylphosphatidylcholine (DPPC) and 1
      palmitoyl-2-oleoylphosphatidylcholine (POPC), respectively) has been studied by
      small-angle X-ray techniques. In liposomal dispersions of DPPC, an osmotically
      stressed liquid-crystalline phase, denoted as Lalpha osm, forms readily after
      rapid mixing with salt solutions. The transition from Lalpha -->Lalpha osm
      proceeds in two steps. The first step takes place within seconds and is due to
      water diffusion from the liposome into the bulk solution. The second, slower
      process (minutes) can be attributed to the relaxation of initially deformed
      intermediate liposomes into spherical ones. In experiments with aligned lipid
      bilayers supported on silicon wafers, it was possible to reproducibly exchange
      different concentrations of LiCl solutions on a single sample and to determine
      the lattice changes by time-resolved X-ray scattering at grazing incidence.
      Independently of the deposition technique (spray- or spin-coating, respectively),
      none of the investigated POPC samples displayed an osmotically stressed liquid
      crystalline phase. While liposomes can be considered nearly defect-free,
      supported bilayer stacks show a high abundance of defects, such as oily streaks
      typical of the Lalpha phase. Thus, the alkali ions are free to diffuse into the
      interbilayer water regions and to cause a slight increase of the bilayer
      separation (about 1 Angstroms). It is concluded that low to medium concentrations
      of Li+ ions partially screen the attractive van der Waals force between adjacent
      membrane layers. However, upon annealing the defect regions or regions of high
      curvature in the oriented lipid matrix, e.g. by low amounts of oleyl alcohol
      (OA), the system is able to sense osmotic stress upon addition of a salt
      solution.

PMID- 15969175
TI  - Effect of actin concentration on the structure of actin-containing liposomes.
AB  - Liposomes encapsulating monomeric actin (G-actin) were produced via extrusion
      through 400 and 600 nm pore diameter polycarbonate membranes in low ionic
      strength buffer (G-buffer). After actin-containing liposomes were subjected to
      high ionic strength polymerization buffer (F-buffer), morphological changes in
      the structure of actin-containing liposomes were studied using asymmetric flow
      field-flow fractionation (AFFF) coupled with multiangle static light scattering
      (MASLS). The general shape of these liposomes was initially determined by fitting
      three form factors, which describe the angular distribution of scattered light
      from a spherical thin shell, thin disk, and thin rod, to the experimentally
      measured light scattering spectra to regress the dimensions of the liposomes
      corresponding to the proposed geometry. Light scattering spectra that yielded a
      best fit to the thin disk model were analyzed further and fit to the ellipsoidal
      of revolution form factor to regress both the major and minor axis dimensions.
      The results of this analysis showed that actin-containing liposomes extruded
      through 400 and 600 nm pore diameter membranes in F-buffer, at a low actin
      concentration (0.1 mg/mL), assumed a spherical shape, which is also the case for
      plain liposomes (no actin present) in G-buffer and F-buffer. When the actin
      concentration was increased to 1 mg/mL, the polymerizing actin filaments
      stretched the initially spherical liposome into a disklike shape. However, when
      the actin concentration was further increased to 5 mg/mL, the liposomes reverted
      back to a spherical shape.

PMID- 15969176
TI  - Surface structural characterization of protein- and polymer-modified polystyrene
      microspheres by infrared-visible sum frequency generation vibrational
      spectroscopy and scanning force microscopy.
AB  - Structural investigations of bare and surface-modified polystyrene microspheres
      (beads) have been carried out by infrared-visible sum frequency generation (SFG)
      vibrational spectroscopy and scanning force microscopy (SFM). Bead surfaces have
      been modified by either the covalent linking of immunoglobulin G (IgG) and bovine
      serum albumin (BSA) or the nonspecific adsorption of a Pluronic surfactant. After
      surface modification with protein, SFG signals in the aliphatic CH-stretch region
      are detected at both the buffer/bead and air/bead interfaces, indicating that
      some amino acid residues in proteins adopt preferred orientations. SFG results
      indicate that the hydrophobic poly(propylene glycol) moieties in the Pluronic
      order when adsorbed onto the bead, at both the buffer/bead and air/bead
      interfaces, whereas hydrophilic poly(ethylene glycol) groups align to a lesser
      extent. SFG spectra also show that the phenyl rings of bare polystyrene beads in
      contact with air or buffer are ordered, with a dipole component directed along
      the surface normal, but become less ordered after the adsorption of either
      proteins or the polymer. Molecular orientation and ordering at the bead surface
      affect its hydrophobicity and aggregation behavior. SFM results reveal the
      formation of nonuniform islands when bare beads with more hydrophobic character
      are spun-cast onto a silica substrate. In the presence of adsorbed protein, a
      hexagonal packing of beads, with some defects, is observed, depending on the bulk
      pH and the type of attached protein. Adsorbed Pluronic causes the beads to
      aggregate in a disordered fashion, as compared to the behavior of bare and
      protein-modified beads.

PMID- 15969177
TI  - Network formation of catanionic vesicles and oppositely charged polyelectrolytes.
      Effect of polymer charge density and hydrophobic modification.
AB  - In nonequimolar solutions of a cationic and an anionic surfactant, vesicles
      bearing a net charge can be spontaneously formed and apparently exist as
      thermodynamically stable aggregates. These vesicles can associate strongly with
      polymers in solution by means of hydrophobic and/or electrostatic interactions.
      In the current work, we have investigated the rheological and microstructural
      properties of mixtures of cationic polyelectrolytes and net anionic sodium
      dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes
      consist of two cationic cellulose derivatives with different charge densities;
      the lowest charge density polymer contains also hydrophobic grafts, with the
      number of charges equal to the number of grafts. For both systems, polymer
      vesicle association leads to a major increase in viscosity and to gel-like
      behavior, but the viscosity effects are more pronounced for the less charged,
      hydrophobically modified polymer. Evaluation of the frequency dependence of the
      storage and loss moduli for the two systems shows further differences in
      behavior: while the more long-lived cross-links occur for the more highly charged
      hydrophilic polymer, the number of cross-links is higher for the hydrophobically
      modified polymer. Microstructure studies by cryogenic transmission electron
      microscopy indicate that the two polymers affect the vesicle stability in
      different ways. With the hydrophobically modified polymer, the aggregates remain
      largely in the form of globular vesicles and faceted vesicles (polygon-shaped
      vesicles with largely planar regions). For the hydrophilic polycation, on the
      other hand, the surfactant aggregate structure is more extensively modified:
      first, the vesicles change from a globular to a faceted shape; second, there is
      opening of the bilayers leading to holey vesicles and ultimately to considerable
      vesicle disruption leading to planar bilayer, disklike aggregates. The faceted
      shape is tentatively attributed to a crystallization of the surfactant film in
      the vesicles. It is inferred that a hydrophobically modified polyion with
      relatively low charge density can better stabilize vesicles due to formation of
      molecularly mixed aggregates, while a hydrophilic polyion with relatively high
      charge density associates so strongly to the surfactant films, due to strong
      electrostatic interactions, that the vesicles are more perturbed and even
      disrupted.

PMID- 15969178
TI  - Conformational dynamics of poly(acrylic acid). A study using surface plasmon
      resonance spectroscopy.
AB  - The conformational dynamics of poly(acrylic acid) induced by pH change is
      reported here. Poly(acrylic acid) immobilized on gold surface was exposed to pH
      changes, and the conformational changes thus induced were followed in real time
      using surface plasmon resonance spectroscopy. The temporal profile of the
      stretching-coiling phenomenon showed a minimum point, which was proposed to be
      arising due to the contradictory behavior of two different property changes in
      the polymeric system. Normally surface plasmon resonance (SPR) response would be
      a convoluted effect of the thickness and refractive index changes, but the
      behavior observed here, where the SPR response is predominantly governed by
      either one of the two, is unique and to the author's knowledge is a feature that
      is observed for the first time. Analysis of the kinetics of the angle change
      revealed that it takes longer for the polymer to stretch than it takes for it to
      collapse, with the kinetic rate constants varying by at least an order of
      magnitude. The SPR angle change as well as the kinetic constants increased
      linearly with molecular weight. Effect of Ca2+ was studied, and it was found that
      the polymer was locked in its conformation due to the binding of the multivalent
      cations.

PMID- 15969179
TI  - Deactivation of the TiO2 photocatalyst by coupling with WO3 and the
      electrochemically assisted high photocatalytic activity of WO3.
AB  - Patterned TiO2 stripes were formed on a sol-gel crystalline WO3 film by using a
      chemically modified sol-gel method (pat-TiO2/WO3), and the coupling effect on the
      photocatalytic activity was studied. Although the photoinduced electron transfer
      from TiO2 to WO3 was confirmed by labeling and visualization of the reduction
      sites with Ag particles, the photocatalytic activities of TiO2 for both the gas
      phase oxidation of CH3CHO and the liquid-phase oxidation of 2-naphthol decreased
      significantly with the coupling. This finding was rationalized in terms of the
      decrease in the rate of the electron transfer from the semiconductor-(s) to 02
      with the coupling, which was estimated from the kinetic analysis of the
      photopotential relaxation. When the excited electrons were removed by a SnO2
      underlayer, the WO3 film exhibited a high photocatalytic activity exceeding that
      of TiO2 for the oxidation of 2-naphthol.

PMID- 15969180
TI  - Two phase transitions of poly(N-isopropylacrylamide) brushes bound to gold
      nanoparticles.
AB  - The thermally induced phase transition of the poly(N-isopropylacrylamide)
      (PNIPAM) brush covalently bound to the surface of the gold nanoparticles was
      studied using high-sensitivity microcalorimetry. Two types of PNIPAM monolayer
      protected clusters (MPCs) of gold nanoparticles were employed, denoted as the
      cumyl- and the cpa-PNIPAM MPCs, bearing either a phenylpropyl end group or a
      carboxyl end group on each PNIPAM chain, respectively. The PNIPAM chains of both
      MPCs exhibit two separate transition endotherms; i.e., the first transition with
      a sharp and narrow endothermic peak occurs at lower temperature, while the second
      one with a broader peak occurs at higher temperature. With increase of the MPC
      concentration, the transition temperature corresponding to the first peak only
      slightly changes but the second transition temperature strongly shifts to lower
      temperature. The calorimetric enthalpy change in the first transition is much
      smaller than that in the second transition. The ratio of the calorimetric
      enthalpy change to the van't Hoff enthalpy change indicates that in the first
      transition PNIPAM segments show much higher cooperativity than in the second one.
      The investigation of pH dependence of two-phase transitions further indicates the
      PNIPAM brush reveals two separate transitions even with a change in
      interchain/interparticle association. The observations are tentatively
      rationalized by assuming that the PNIPAM brush can be subdivided into two zones,
      the inner zone and the outer zone. In the inner zone, the PNIPAM segments are
      close to the gold surface, densely packed, less hydrated, and undergo the first
      transition. In the outer zone, on the other hand, the PNIPAM segments are looser
      and more hydrated, adopt a restricted random coil conformation, and show a phase
      transition, which is dependent on both concentration of MPC and the chemical
      nature of the end groups of the PNIPAM chains. Aggregation of the particles,
      which may also affect the phase transition, is briefly discussed.

PMID- 15969181
TI  - Preparation, characterization, and solution viscosity of polystyrene-block
      polyisoprene nanofiber fractions.
AB  - A polystyrene-block-polyisoprene (PS-b-PI) sample with 130 styrene and 370
      isoprene units was synthesized and characterized. The diblock formed mostly
      cylindrical micelles in N,N-dimethylacetamide with a PI core and a PS corona. The
      PI core of the micelles was cross-linked by S2Cl2 to yield nanofibers. The
      nanofibers were shortened by ultrasonication to yield fractions withweight
      average length (Lw) between approximately 900 and approximately3400 nm.
      Transmission electron microscopy and light scattering were used to characterize
      the fractions. The zero-shear intrinsic viscosity data [eta] of the fractions
      were obtained in tetrahydrofuran (THF), THF/N,N-dimethylformamide (DMF), and
      THF/cyclohexane (CHX), where THF is a good solvent for both the corona and the
      core, DMF solubilizes only the corona, and CHX is a theta solvent for the corona
      chains at 34.5 degrees C. The [eta] data of the fractions were treated by the
      Bohdanecky method derived from the Yamakawa-Fujii-Yoshizaki (YFY) theory for
      wormlike polymer chains and yielded the persistence length lP and the
      hydrodynamic diameters dh for the nanofibers. The reasonable dh values and the
      reasonable trend of dh variation with solvent quality change establish
      unambiguously the validity of YFY theory.

PMID- 15969182
TI  - Deposition of poly(styrene/alpha-tert-butoxy-omega-vinyl-benzyl-polyglycidol)
      microspheres on mica plates crossing the liquid-air interface: formation of
      stripe pattern.
AB  - Formation of stripelike assemblies of poly(styrene/alpha-tert-butoxy-omega-vinyl
      benzyl-polyglycidol) microspheres adsorbed on nonpatterned mica plates moving
      perpendicularly from suspension of particles through the water-air interface has
      been observed. It was found that ordered assemblies were formed by capillary
      forces acting on particles crossing the water-air boundary. At sufficiently high
      rates of plate movement (i.e., at appropriate dynamic loading conditions) the
      adsorbed microspheres approaching the water surface begin sliding on the plate,
      due to capillary forces, in the direction opposite to the plate movement and are
      kept below the water surface. Plate movement brings new adsorbed particles to the
      water-air interface, where particles are assembled into aggregates. When particle
      aggregates are large, the capillary forces cannot overcome shearing forces and
      the particle assemblies are withdrawn on the plate above the water surface. This
      process repeated during continuous movement of the plate results in the formation
      of the quite regularly distributed stripes of adsorbed microspheres. Formation of
      the regularly distributed particle assemblies depends on concentration of
      microspheres in suspension.

PMID- 15969183
TI  - Reductive deposition of Rh nanostructures on n-type porous silicon: X-ray
      absorption and X-ray excited optical luminescence studies.
AB  - 22Porous silicon (PS) prepared from an n-type Si(100) wafer was utilized as a
      reducing agent and a nanosubstrate for the reduction of rhodium complex ions
      [RhCl6]3- from aqueous solution to metallic Rh nanostructures on the surface of
      the n-type PS. The morphology and the electronic properties of the PS layers as
      well as the rhodium nanostructures were studied by field emission scanning
      electron microscopy, X-ray absorption fine structures spectroscopy, and X-ray
      excited optical luminescence (XEOL). The average particle size of Rh
      nanostructures on PS was estimated to be approximately 7 nm by the X-ray
      diffraction pattern. The specificity ofXEOL allowed for the investigation of the
      effect of Rh nanostructures on the optical properties of PS.

PMID- 15969184
TI  - Size-dependent properties of nanocrystalline silicalite synthesized with
      systematically varied crystal sizes.
AB  - Silicalite-1 powders with crystal sizes ranging from 20 to 1000 nm were
      synthesized by systematically varying synthesis gel composition, pressure,
      temperature, and time duration. These samples were characterized by powder X-ray
      diffraction, scanning electron microscopy, nitrogen adsorption isotherms, solid
      state nuclear magnetic resonance, and toluene adsorption. The effect of crystal
      size on the physical properties of crystals is observed, including a large
      increase of both total and external surface area when crystal size decreases. The
      relationship between particle size and external surface area was modeled by
      assuming a cubic crystal geometry. The nanosized silicalite samples with crystal
      sizes less than 100 nm have a higher adsorption capacity for toluene, showing
      promising potential for its application in volatile organic compound removal.

PMID- 15969185
TI  - Substituent effects on the exchange dynamics of ligands on 1.6 nm diameter gold
      nanoparticles.
AB  - The kinetics of exchange ofphenylethanethiolate ligands (PhC2S) of monolayer
      protected clusters (MPCs, average formula Au140(PhC2S)53) by para-substituted
      arylthiols (p-X-ArSH) are described. 1H NMR measurements of thiol concentrations
      show that the exchange reaction is initially rapid and gradually slows almost to
      a standstill. The most labile ligands, exchanging at the shortest reaction times,
      are thought to be those at defect sites (edges, vertexes) on the nanoparticle
      core surface. The pseudo-first-order rate constants derived from the first 10% of
      the exchange reaction profile vary linearly with in-coming arylthiol
      concentration, meaning that the labile ligands exchange in a second-order
      process, which is consistent with ligand exchange being an associative process. A
      linear Hammett relationship with slope p = 0.44 demonstrates a substituent effect
      in the ligand place exchange reaction, in which the bimolecular rate constants
      increase for ligands with electron-withdrawing substituents (1.4 x 10-2 and 3.8 x
      10(-3) M(-1) s(-1) for X = NO2 and 4-OH, respectively). This is interpreted as
      the more polar Au-S bonds at the defect sites favoring bonding with more electron
      deficient sulfur moieties. At longer reaction times, where ligands exchange on
      nondefect (terrace) as well as defect sites, the extent of ligand exchange is
      higher for thiols with more electron-donating substituents. The difference
      between short-time kinetics and longer-time pseudoequilibria is rationalized
      based on differences in Au-S bonding at defect vs nondefect MPC core sites. The
      study adds substance to the mechanisms of exchange of protecting ligands on
      nanoparticles. The scope and limitations of 1H NMR spectroscopy for determining
      rate data are also discussed.

PMID- 15969186
TI  - Pervaporation from a dense membrane: roles of permeant-membrane interactions,
      Kelvin effect, and membrane swelling.
AB  - Dense polymeric membranes with extremely small pores in the form of free volume
      are used widely in the pervaporative separation of liquid mixtures. The membrane
      permeation of a component followed by its vaporization on the opposite face is
      governed by the solubility and downstream pressure. We measured the evaporative
      flux of pure methanol and 2-propanol using dense membranes with different free
      volumes and different affinities (wettabilities and solubilities) for the
      permeant. Interestingly, the evaporative flux for different membranes vanished
      substantially (10-75%) below the equilibrium vapor pressure in the bulk. The
      discrepancy was larger for a smaller pore size and for more wettable membranes
      (higher positive spreading coefficients). This observation, which cannot be
      explained by the existing (mostly solution-diffusion type) models
      ofpervaporation, suggests an important role for the membrane-permeant
      interactions in nanopores that can lower the equilibrium vapor pressure. The pore
      sizes, as estimated from the positron annihilation, ranged from 0.2 to 0.6 nm for
      the dry membranes. Solubilities of methanol in different composite membranes were
      estimated from the Flory-Huggins theory. The interaction parameter was obtained
      from the surface properties measured by the contact angle goniometry in
      conjunction with the acid-base theory of polar surface interactions. For the
      membranes examined, the increase in the "wet" pore volume due to membrane
      swelling correlates almost linearly with the solubility of methanol in these
      membranes. Indeed, the observations are found to be consistent with the lowering
      of the equilibrium vapor pressure on the basis of the Kelvin equation. Thus, a
      higher solubility or selectivity of a membrane also implies stronger permeant
      membrane interactions and a greater retention of the permeant by the membrane,
      thus decreasing its evaporative flux. This observation has important implications
      for the interpretation of existing experiments and in the separation of liquid
      mixtures by pervaporation.

PMID- 15969187
TI  - Luminescence properties of rhodamine 6G intercalated in surfactant/clay hybrid
      thin solid films.
AB  - To develop the solid-state laser oscillator based on laser dye compounds, the
      incorporation of rhodamine 6G (R6G, a laser dye) in cetyltrimethylammonium (CTA+)
      cationic surfactant/montmorillonite clay hybrid (HpC) thin solid films was
      investigated. The R6G/HpC samples were prepared by immersing the HpC films into a
      R6G aqueous solution with various concentration. X-ray diffraction patterns of
      the films of HpC, measured before and after the intercalation of R6G, proved the
      coexistence of both the dye and surfactant in clay interlayer spaces. All
      prepared thin films exhibited luminescence. It indicates that CTA+ molecules play
      a role as a partial suppressor of the aggregation of R6G molecules which prevents
      fluorescence. Moreover, the luminescence property of the present thin films was
      observed to be dependent on the co-intercalated degree of R6G molecules,
      indicating that the R6G intercalating in HpC interlayer space molecules exist as
      two or more luminescence species in the clay interlayer space.

PMID- 15969188
TI  - Surface functionalization of silicon nanoparticles produced by laser-driven
      pyrolysis of silane followed by HF-HNO3 etching.
AB  - CO2 laser induced pyrolysis of silane was used to produce silicon nanoparticles
      with an average diameter as small as 5 nm at high rates (up to 200 mg/h). Etching
      these particles with a mixture of hydrofluoric acid (HF) and nitric acid (HNO3)
      reduces their size and passivates their surface such that they exhibit bright
      visible photoluminescence (PL). This paper describes the attachment of organic
      molecules to hydrogen-terminated and hydroxyl-terminated surfaces of these
      nanoparticles. Stable particle dispersions in various solvents were obtained by
      treatment of hydrogen-terminated surfaces with octadecene or undecylenic acid and
      by treatment of hydroxyl-terminated surfaces with octadecyltrimethoxysilane.
      Transmission electron microscopy showed that the surface-functionalized particles
      were well dispersed and crystalline. FTIR spectroscopy confirmed the expected
      reactions of the organic molecules with the particle surfaces. Photoluminescence
      measurements showed that surface treatment significantly stabilized the PL
      properties of the nanoparticles against degradation. Size selective precipitation
      was applied to particle dispersions and allowed some narrowing and tuning of the
      PL spectrum.

PMID- 15969189
TI  - Amine-terminated dendrimers as biomimetic templates for silica nanosphere
      formation.
AB  - In diatoms, silica synthesis occurs by use of complex posttranslationally
      modified peptides, termed silaffins, and highly complex biological polyamine
      structures. Silaffin peptides have lysine residues that are modified to long
      chain polyamine moieties of N-methyl derivatives of polypropylenimine to drive
      silica synthesis at slightly acidic pH conditions. Using polypropylenimine (PPI)
      and PAMAM amine-terminated dendrimers as a biomimetic analogue of the polyamine
      modifications of silaffins, we have demonstrated the condensation of silica
      nanospheres. We have shown that the dendrimers react in an amine concentration
      dependent fashion yielding silica nanospheres with a distinct size distribution
      reminiscent of the structures produced from both the modified and nonmodified
      peptides extracted from diatoms. Additionally, the templates were encapsulated by
      the growing nanospheres and precipitated from solution in a manner similar to
      that previously described for the bioactive peptides and polyamines.

PMID- 15969190
TI  - Reversible encapsulation of nanometer-size polyaniline and polyaniline-Au
      nanoparticle composite in starch.
AB  - In this paper we report a new method of solubilization of polyaniline and
      polyaniline-Au-nanoparticle composite by encapsulating nanometer-size particles
      in starch. The solubilization was carried out in the presence of ultrasonic
      waves. We also report that the encapsulation was completely reversible and the
      dissolved polyaniline as well as the composite could be recovered by replacement
      with molecular iodine. In addition, the polymer particles could also replace
      molecular iodine from starch-iodine complex. UV-Visible and Fourier transform
      infrared (FTIR) spectroscopic measurements established the reversible nature of
      encapsulation. Transmission electron microscopic measurements showed that the
      sizes of the particles encapsulated in starch were on the order of 10-20 nm for
      both polyaniline and Au-nanoparticle-polyaniline composite particles. X-ray
      diffraction evidenced the presence ofAu-nanoparticles in the starch-polyaniline
      Au-nanoparticle composite. Finally, we also mention here that the dissolved
      polyaniline could also be recovered as a precipitate by enzyme (diastage)
      hydrolysis of the polyaniline encapsulating starch.

PMID- 15969191
TI  - Hydrophilic elastomers for microcontact printing of polar inks.
AB  - A moderately hydrophilic, thermoplastic elastomer (poly(ether-ester)) was
      investigated as a stamp material for microcontact printing of a polar ink:
      pentaerythritol-tetrakis-(3-mercaptopropionate). Stamps with a relief structure
      were produced from this polymer by hot embossing, and a comparison was made with
      conventional poly(dimethylsiloxane) (PDMS) and oxygen-plasma-treated PDMS. It is
      shown that the hydrophilic stamps can be used for the repetitive printing
      (without re-inking) of at least 10 consecutive patterns, which preserve their
      etch resistance, and this in rather sharp contrast to conventional and oxygen
      plasma-treated PDMS stamps. It is argued that these enhanced printing
      characteristics of the hydrophilic stamps originate from an improved wetting and
      solubility of polar inks in the hydrophilic stamp.

PMID- 15969192
TI  - Modeling desorption of fluids from disordered mesoporous materials.
AB  - The desorption mechanism of fluids in disordered mesoporous glasses is studied by
      Monte Carlo simulations of a coarse-grained lattice model with realistic matrix
      configurations representative of Vycor. Two methods of simulation are considered:
      grand canonical ensemble Monte Carlo simulations and dynamic Monte Carlo
      simulations which mimic the diffusion of the fluid in and out of the material
      using Kawasaki dynamics. In the grand canonical simulations, cavitation via
      nucleation of bubbles inside the pores plays the dominant role in determining the
      fluid configurations along the desorption isotherm. The Kawasaki dynamics
      simulations indicate that such configurations are achieved dynamically via the
      gradual advancement of macroscopic front interfaces toward the interior. This is
      made possible by the bubble nucleation mechanism operating on a length scale that
      is determined by both the typical pore size and the strength of the solid-fluid
      interaction.

PMID- 15969193
TI  - Low inertia impact dynamics for nanodrops.
AB  - Simulations of a droplet impacting a flat solid surface with a small initial
      speed have been studied using molecular dynamics. Approximating the shape of the
      drop by a spheroid, spreading radii, and dynamic contact angles are measured. The
      data reproduce well experimental results from literature. We show that the
      difference between the equilibrium and the dynamic contact angle cosines, that
      is, the spontaneous driving force, versus the spreading velocity of the three
      phase line varies with impact speed and consists of two distinct regimes which
      can be described by existing models of moving contact lines.

PMID- 15969194
TI  - Water at hydrophobic substrates: curvature, pressure, and temperature effects.
AB  - We studied the water density profile close to spherical and planar hydrophobic
      objects using molecular dynamics (MD) simulations. For normal pressure and room
      temperature, the depletion layer thickness of a planar substrate is approximately
      2.5 Angstroms. Even for quite large spherical solutes with a radius of R = 18
      Angstroms, the depletion layer thickness is reduced by 30%, which shows that
      substrate curvature and roughness is an experimentally important factor. Rising
      temperature leads to a substantial increase of the depletion layer thickness. The
      compressibility of the depletion layer is found to be surprisingly small and only
      approximately 5 times higher than that of bulk water. A high electrostatic
      surface potential of 0.5 V is found, which presumably plays an important role in
      the presence of charged solutes, since it can promote adsorption into the
      interfacial layer.

PMID- 15969195
TI  - Cylindrical cell model for the electrostatic free energy of polyelectrolyte
      complexes.
AB  - Associative phase separation (complex coacervation) in a mixture of oppositely
      charged polyelectrolytes can lead to different types of (inter-)polyelectrolyte
      complexes (soluble micelles, macroscopic precipitation). In a previous report
      [Langmuir 2004, 20, 2785-2791], we presented a model for the electrostatic free
      energy change when (weakly charged) polyelectrolyte forms a homogeneous complex
      phase. The influence of ionization of the polymer on the electrostatic free
      energy of the complex was incorporated but the influence of complex density
      neglected. In the present effort, cylindrical cells are assumed around each
      polyelectrolyte chain in the complex, and on the basis of the Poisson-Boltzmann
      equation, the electrostatic free energy is calculated as a function of the
      complex density. After combination with Flory-Huggins mixing free energy terms
      and minimization of the total free energy, the equilibrium complex density is
      obtained, for a given ratio of polycations to polyanions in the complex. The
      analysis is used in an example calculation ofpolyelectrolyte film formation by
      alternatingly applying a polycation and a polyanion solution. The calculation
      suggests that the often observed exponential growth of a polyelectrolyte film
      when the polymer is weakly charged has a thermodynamic origin: the
      polyelectrolyte complex shifts repeatedly between two equilibrium states of
      different densities and compositions. However, when the polyelectrolytes are
      strongly charged the difference in the compositions between the two equilibrium
      states is very small, and exponential growth by an absorption mechanism is no
      longer possible.

PMID- 15969196
TI  - Formation of nanoscopic foam in instantaneously heated sol-gel derived silica.

PMID- 15969197
TI  - Peptide attachment to vapor deposited polymeric thin films.

PMID- 15969198
TI  - High aqueous solubility of functionalized single-walled carbon nanotubes.

PMID- 15969199
TI  - Determination of the size of a polystyrene nanosphere by the pulsed field
      gradient nuclear magnetic resonance method.

PMID- 15969200
TI  - Topography of the rutile TiO2(110) surface exposed to water and organic solvents.

PMID- 15969201
TI  - Preparation of ultrahigh-aspect-ratio hydroxyapatite nanofibers in reverse
      micelles under hydrothermal conditions.

PMID- 15969202
TI  - Determination of some organochlorine compounds in herbal colouring agent henna
      (Lawsonia inermis) and in tea (Thea sinensis).
AB  - Henna (Lawsonia inermis) has been used for centuries as a herbal hair and skin
      dye, but very little is known about its additives and contaminants that could
      adversely affect human health. An analytical method was developed to determine
      organochlorine compounds in henna, as they are still widely used in the areas
      where henna is grown. Samples were sonicated with n-hexane, extracts cleansed on
      Florisil sorbent and analysed using gas chromatography with electron capture
      detection. The overall recoveries were 17-33 % with the extraction RSD 5-21%,
      while the levels of lindane (gamma-HCH), p,p'-DDT, and p,p'-DDE in henna samples
      were 7-157 microg kg(-1). The same procedure was successfully applied to analyse
      black tea samples for the same compounds, and which showed lower contamination.

PMID- 15969203
TI  - Mercury chloride genotoxicity in rats following oral exposure, evaluated by comet
      assay and micronucleus test.
AB  - Mercury is a toxic element which is easily absorbed after ingestion or inhalation
      and deposited mainly in the kidney. The aim of this study was to evaluate the
      effects of mercury chloride in rats. Female rats, aged 14 weeks, were receiving
      mercury chloride in oral doses of 0.068, 0.136, and 0.272 mg kg(-1) body weight
      (b.wt.) for five consecutive days. Three days after the last dose, the animals
      were killed. The liver and the kidney were dissected and mercury measured using
      vapour generation atomic absorption spectrometry. The results show a significant
      increase in mercury mass fraction in the kidney after two higher doses of mercury
      chloride, while liver mercury burden showed a significant increase only after the
      highest dose. Blood samples were analysed using the comet assay and supravitally
      acridine orange stained micronucleus test. Tail length, tail moment and
      micronucleus frequency were significantly higher in the treated rats than in
      control rats, regardless of the dose of mercury chloride, while the difference
      between the treated groups for both comet and micronucleus parameters was not
      statistically significant.

PMID- 15969204
TI  - Ochratoxin A in wine.
AB  - A high-performance liquid chromatography (HPLC) method for determination of
      ochratoxin A (OTA) in wine was developed and checked on 14 samples of wine
      produced in the Republic of Croatia. OTA detection in red and white wine was
      validated checking the linearity of the method (r2=0.997 and 0.999,
      respectively), recovery (88 and 95 %, respectively), and precision (RSD=3.1 and
      1.4 %, respectively). The detection limit of OTA in both red and white wine was
      10 ng L(-1). The OTA concentration in all red wines was above the detection limit
      (mean 22+/-11 ng L(-1)), while only 4 of 7 white wines contained OTA (mean 10+/-9
      ng L(-1)). Three OTA-free white wines were from the north of Croatia (inland),
      while all wines produced in the south (Adriatic coast) were OTA-positive.
      However, the concentrations were too low to present a risk for a moderate wine
      consumer.

PMID- 15969205
TI  - [Hazardous medical waste management as a public health issue].
AB  - The amount of waste produced is connected with the degree of a country's economic
      development; more developed countries produce more waste. This paper reviews the
      quantities, manipulation and treatment methods of medical waste in Croatia, as
      well as hazardous potentials of medical waste for human health. Medical waste
      must be collected and sorted in containers suitable for its characteristics,
      amount, means of transportation and treatment method in order to prevent contact
      with environment and to protect people who are working with waste. Hazardous
      medical waste in Croatia is largely produced by hospitals. Even though only one
      hospital has a licence to incinerate infectious medical waste, many other
      hospitals incinerate their hazardous waste in inappropriate facilities.
      Healthcare institutions also store great amounts of old medical waste, mostly
      pharmaceutical, anti-infectious, and cytostatic drugs and chemical waste. Data on
      waste treatment effects on human health are scarce, while environmental problems
      are covered better. Croatian medical waste legislation is not being implemented.
      It is very important to establish a medical waste management system that would
      implement the existing legislation in all waste management cycles from waste
      production to treatment and final disposal.

PMID- 15969206
TI  - A lighter side of calcium: role of calcium and dairy foods in body weight.
AB  - This review explains the physiological involvement of calcium in
      overweight/obesity (as it is understood now) and presents some of the studies
      where this role has been documented, as well as those reporting no effect of Ca
      on body weight/composition. Based on much of the presently reported data, Ca and
      even more so dairy foods, might help in weight reduction/maintenance when
      combined with energy-restricted diet. The scientific community is in agreement
      that there is a pressing need for large clinical trials to assess the effect of
      Ca on weight reduction and to investigate whether weight loss could be achieved
      easier with Ca supplements or dairy products. It has yet to be learned what
      amount of Ca would be optimal for those purposes and what influence, if any, an
      individual's current Ca intake and existing weight might play. Additionally, it
      is still hard to pinpoint which component(s) in dairy foods have a role in weight
      reduction and whether they act alone or in synergism with Ca. Considering the
      overwhelming prevalence of overweight/obesity and consequences to population
      health and economic burden it entails, it is of crucial importance to develop
      strategies to curtail the problem of obesity from all fronts and the one
      involving Ca seems quite promising. However, more research in this area is
      necessary.

PMID- 15969207
TI  - [Effects of sodium chloride on bone health].
AB  - This paper discusses the physiology of sodium effects on calcium metabolism and
      possible implications of increased salt intake on bone remodelling and bone mass.
      Osteoporosis is an increasing public health problem affecting more than 200
      million of women around the world. The major complications of osteoporosis are
      fractures, which are frequently associated with high morbidity and mortality. A
      number of clinical, epidemiological and experimental studies aim at identifying
      lifestyle factors that may improve bone mass and prevent bone loss. Different
      nutrients are proposed to play a role in bone development during growth and in
      the maintenance of bone mass thereafter. However, the importance of sodium intake
      for bone health has not been elucidated. It is well known that high dietary
      sodium intake decreases renal calcium reabsorption, which in turn leads to a
      greater urinary calcium excretion. This effect has been demonstrated in studies
      in humans of all ages as well as in experimental animals. It is not clear to what
      extent sodium-induced calcium loss is compensated for by increased intestinal
      calcium absorption. It is suspected that, if not fully compensated, sustained
      hypercalciuria due to increased sodium intake may diminish bone mass.
      Postmenopausal women showed that increased dietary salt may indeed augment bone
      resorption. Sodium effects on bone mass in various studies are inconsistent and
      there is still no evidence that increased salt intake is a risk factor in the
      aetiology of osteoporosis A randomized longitudinal study of different sodium
      intake in two groups of subject could clarify the role of sodium in bone mass.

PMID- 15969208
TI  - [Capsular polysaccharide antibodies after pneumococcal polysaccharide vaccination
      in patients with chronic respiratory disease].
AB  - We investigated the antibody response to a 23-valent pneumococcal polysaccharide
      vaccine (23PSV), in 151 patients (average age: 70 years old) with chronic
      respiratory disease. Serotype-specific IgG antibodies to 4 pneumococcal capsular
      polysaccharides (6B, 14, 19F, and 23F) were analyzed by ELISA before, and one
      month after, 23PSV vaccination in all patients. Patients showed a significant
      increase in specific IgG levels to Streptococcus pneumoniae after 23PSV
      vaccination (5.5 times-20.9 times). Even patients aged over 80, patients with
      respiratory failure, and patients receiving corticosteroid therapy developed a
      significant immunologic response to 23PSV. Local pain or induration occurred in
      9.1-14.3% and fatigue or chills occurred in 0.7-6.5% of patients. All adverse
      reactions disappeared in 2 or 3 days and there was no severe adverse events.
      Further studies are needed to confirm the exact protective antibody level and to
      examine the decline of antibody level after vaccination.

PMID- 15969209
TI  - [Effects of peroxisome proliferator-activated receptor gamma ligands on
      monocrotaline-induced pulmonary hypertension in rats].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the
      nuclear hormone receptor superfamily, which regulates transcription of target
      genes in a ligand-dependent manner. Ligands for PPARgamma have been shown to
      attenuate proliferation of vascular smooth muscle cells, and to induce apoptosis
      in several cell lines in vitro. Since monocrotaline (MCT)-induced pulmonary
      hypertension in rats is characterized by proliferation of pulmonary vascular
      smooth muscle cells, we hypothesized that PPARgamma ligands may reduce MCT
      induced pulmonary hypertension. To test this hypothesis, we treated MCT-injected
      rats with pioglitazone and troglitazone, synthetic ligands for PPARgamma, for
      three weeks and measured pulmonary artery pressure and pulmonary vessel wall
      thickness. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunostaining
      for proliferating cell nuclear antigen (PCNA) were utilized to assess apoptosis
      and cell proliferation in the pulmonary arterial walls of pioglitazone-treated
      rats. MCT with pioglitazone or troglitazone treatment significantly reduced
      pulmonary hypertension and wall thickening of the pulmonary arteries. TUNEL
      positive apoptotic cells were not seen in the pulmonary arterial walls of either
      MCT-injected or control rats with or without pioglitazone. PCNA-positive cells
      were only seen in the thickened pulmonary arterial walls of MCT rats, but not in
      the pulmonary arterial walls of controls and of pioglitazone-treated MCT rats. We
      conclude that PPARgamma ligands reduce MCT-induced pulmonary hypertension and
      pulmonary vascular wall thickening in rats. Inhibition of MCT-induced cell
      proliferation in the pulmonary arterial walls may account for this effect

PMID- 15969210
TI  - [A case of chronic obstructive pulmonary disease (COPD) successfully treated by
      acupuncture].
AB  - Chronic obstructive pulmonary disease (COPD) involves a decrease in respiratory
      function and limits daily activities. We report a COPD patient whose respiratory
      symptoms were improved by acupuncture treatment. A 66-year-old man visited Gifu
      University Hospital with breathlessness on exercise. Despite medication, his
      general condition worsened. A series of acupuncture treatments was subsequently
      started on October 27, 2001. He had level III breathlessness on JRS
      classification prior to acupuncture treatment, and his respiratory function
      parameters were VC: 3.54 L, FEV1: 1.19 L, FEV1% (G): 33.6% and %FEV1: 45%. The
      basic meridian points used were KI 3 (Fuliu), LU 9 (Taiyuan), LU 1 (Zhongfu), CV
      12 (Zhongwan), CV 4 (Guanyuan), BL 13 (Feishu), and BL 23 (Shenshu). The
      acupuncture needles were retained for ten minutes in each session. This research
      design was used to detect the specific efficacy of acupuncture treatment After
      ten acupuncture treatments over two months, his walking distance, Borg scale and
      respiratory function were improved compared with before treatment. These findings
      suggest that acupuncture treatment may be efficacious for advanced cases of COPD.

PMID- 15969211
TI  - [Spinal cord metastases in lung cancer: a clinical review of four cases].
AB  - We report 4 cases of spinal cord metastases of lung cancer detected by MRI.
      Histologically, 3 of the 4 cases were small cell carcinoma and the other was
      adenocarcinoma. All 3 cases of small cell carcinoma had neoplastic meningitis.
      MRI taken in these cases showed the multiple nodules in the cauda equina, which
      were seeded from brain metastases. One of them had intramedullary spinal cord
      metastases, which appeared as enlargement of the spinal cord or nodules in the
      spinal cord on MRI. Leg paralysis and incontinence progressed in all cases. The
      other case of adenocarcinoma had epidural spinal cord compression due to spinal
      metastasis. In this case irradiation and corticosteroids relieved her leg and
      back pain. Spinal cord metastases should be considered as a differential
      diagnosis in patients with numbness, pain or weakness in the extremities.

PMID- 15969212
TI  - [A case of arc welder's lung with ground-glass opacities and progressive massive
      fibrosis].
AB  - A 62-year-old man who had worked as a welder for 35 years was admitted with
      abnormal chest radiograph shadows. Chest CT scan showed ground-glass opacities
      (GGO) and nodular shadows (progressive massive fibrosis: PMF) with spiculation in
      both lung fields. Transbronchial lung biopsy (TBLB) findings of a nodule (left
      segment 8) revealed many iron particles in the alveoli and positive staining for
      Fe (Berlin blue stain). Moreover, bronchoalveolar lavage (BAL) fluid of a GGO
      (left segment 4) revealed many iron particles and positive staining for Fe
      (Berlin blue stain) in macrophages. Serum ferritin was extremely high (6.352
      ng/ml) and ferritin in the BAL fluid was 210 ng/ml. Taking the clinical course
      and pathological findings together, pneumoconiosis (arc welder's lung) was
      diagnosed. The most common chest CT pattern in arc welder's lung is ill-defined
      micronodules diffusely distributed in the lung like hypersensitivity pneumonitis.
      Arc welder's lung rarely presents as PMF. We report a case of arc welder's lung
      accompanied with PMF.

PMID- 15969213
TI  - [A patient with pleural thickening of sarcoidosis].
AB  - We report a 51-year-old woman with characteristic pleural involvement of
      sarcoidosis. Video-assisted thoracoscopic examination identified diffuse pleural
      thickening in the right lung, which coincided in distribution with parenchymal
      reticular shadows demonstrated with high-resolution thoracic CT scan. Biopsied
      specimens revealed epithelioid cell granuloma with noncaseating necrosis and
      multi-nucleated giant cells in the parenchymal lung tissue. Infiltration of
      inflammatory cells was demonstrated in the thickened pleural tissue, but no
      typical sarcoid lesion. This pleural lesion was considered as pleural involvement
      of sarcoidosis, since deterioration of the pleural thickening was accompanied
      with progression of a parenchymal sarcoid lesion during the period of two months
      after biopsy. Video-assisted thoracoscopy and high-resolution CT scan both
      supported the diagnosis of sarcoidosis with pleural involvement.

PMID- 15969214
TI  - [A case of non-mucin-producing papillary adenocarcinoma with a 19-year clinical
      history before operation].
AB  - A 73-year-old woman was admitted to our hospital for investigation of an abnormal
      shadow in the right upper lung field. Every year she had a medical check up since
      1983 and the abnormal shadow was repeatedly pointed out However, she had not
      undergone a detailed examination. When she had a medical check up in July 2001,
      the shadow slightly increased compared with the previous chest film. Chest CT
      showed the mass with a pleural indentation in the right S3a, measuring 4 x 4 cm
      in size. Despite examinations including bronchoscopy we could not make a
      definitive diagnosis. After we explained the situation to her, she decided to
      have an operation. The biopsy during the operation revealed adenocarcinoma and
      right upper lobectomy with nodal dissection was performed. The ultimate diagnosis
      was non-mucin-producing papillary adenocarcinoma. This stage IB case was pT2N0M0.
      We reported this case because it was a rare slow-growing papillary adenocarcinoma
      that did not produce mucin and had a 19-year clinical history before operation.

PMID- 15969215
TI  - [A case of sarcoidosis with diffuse pulmonary arteriovenous malformations].
AB  - A 27-year-old woman was admitted because of right dry eye and blurred vision. She
      was given a diagnosis of uveitis due to sarcoidosis. Chest X-ray film showed
      bilateral hilar lymphadenopathy and multiple nodules in both lungs. The nodules
      were considered to be associated with sarcoidosis. However chest CT demonstrated
      that the nodules were well-defined and connected with two vessels. We diagnosed
      diffuse pulmonary arteriovenous malformations (AVMs) by 3D-CT. In three of
      sixteen AVMs, the feeding vessels were more than 3 mm wide in diameter on
      pulmonary arteriography, and those were embolized by platinum coils. The
      embolotherapy of diffuse AVMs could not ameliorate the shunt fraction
      sufficiently, but should reduce the possibility of the catastrophic complication
      of brain abscess.

PMID- 15969216
TI  - [A case of pneumonitis induced by CDDP and 5-FU].
AB  - A 60-year-old man was admitted to our Department of Urology because of the lack
      of effectiveness of CHOP therapy for a retroperitoneal tumor. The tumor was
      finally diagnosed as poorly differentiated adenocarcinoma by CT-guided needle
      biopsy. He received combination chemotherapy with CDDP and 5-FU. After the end of
      this therapy, he noticed dyspnea and cough. He was referred to our department and
      a diagnosis of drug-induced pneumonitis was made because of diffuse shadows in
      bilateral lung fields, 67Ga citrate scintigraphy, his clinical course and
      histological examination of TBLB specimens. He received steroid therapy including
      methylprednisolone pulse therapy, after which his symptoms and abnormal chest
      findings improved. Although lymphocyte stimulation tests by CPA, DXR, VCR, CDDP
      and 5-FU were negative, it was suggested that CPA primed and 5-FU induced the
      pneumonitis in this patient judging from past literatures.

PMID- 15969217
TI  - [Placement of an ultraflex nitinol stent for severe tracheobronchial obstruction
      in a case of relapsing polychondritis].
AB  - A 59-year-old man, who had been treated for bronchial asthma since 2000, was
      hospitalized with high fever and productive cough in November 2003. Chest
      radiography on admission showed consolidations in both lower lung fields, and
      computed tomography demonstrated anteroposterior narrowing of both main bronchi.
      A physical examination revealed deformity of auricular cartilage and saddle nose,
      and we diagnosed him relapsing polychondritis (RP). When he was readmitted 4
      months later because of severe tracheobronchial stenosis and respiratory failure
      he required mechanical ventilation, but it was difficult to wean him from the
      ventilator. Self-expandable metallic stents were placed in the left main bronchus
      and the trachea. After the procedure, he was successfully weared from mechanical
      ventilation. Since airway complications of RP can be fatal, stent implantation
      should be considered in the management of RP with airway manifestations.

PMID- 15969218
TI  - Underfunded mandates or misplaced priorities.

PMID- 15969219
TI  - Parental distress: the initial phase of hearing aid and cochlear implant fitting.
AB  - The results of previous cross-section studies suggest that childhood hearing
      impairment may lead to parental psychosocial stress. The present study
      investigated whether modifications in parental psychic state can be ascertained
      in connection with the child's treatment events and the child's hearing and
      speech status, in a prospective study design. Data were available on 116 fathers
      and mothers regarding the pre-cochlear implant examination or hearing aid fitting
      of their child. In the course of the child's treatment, parental quality of life
      improved from a low to a normal level. Among children who were at the stage of
      pre-examination for a cochlear implant, better hearing and speech capacity was
      linked to more severe impairment of the parental state. It is emphasized that the
      parents whose children showed comparatively good language development at the time
      of pre-examination for a cochlear implant were especially subjected to stress.

PMID- 15969220
TI  - Mental health problems of Dutch youth with hearing loss as shown on the Youth
      Self Report.
AB  - The prevalence OF mental health problems among youth with hearing loss was
      assessed with an adjusted version of the Dutch rendition of the Youth Self
      Report, or YSR (Achenbach, 1991). The sample totaled 202 youth, aged 11-18 years,
      with auditory disabilities. The prevalence rates of externalizing problems,
      internalizing problems, and moderate to severe overall mental health problems
      were found to be 2-3 times higher than in a normative sample. Deaf participants
      scored significantly higher than hard of hearing participants in these areas.
      Main-streamed participants scored significantly lower than peers in schools for
      the deaf or for the hard of hearing. Participants with low IQ scores showed
      significantly more internalizing and social problems than those with moderate to
      high scores. The adjusted YSR is recommended for screening in schools and in
      mental health services for youth with hearing loss for prevention and early
      intervention.

PMID- 15969221
TI  - Professional concerns of beginning teachers of deaf and hard of hearing students.
AB  - The professional concerns of beginning teachers of students who are deaf or hard
      of hearing were examined. Five first-year teachers of deaf and hard of hearing
      students served as participants. Two of the participants were itinerant teachers;
      three taught in self-contained classrooms. Participants were selected from
      programs serving deaf and hard of hearing students in rural and urban areas of
      the midwestern and southwestern United States. To interview the study
      participants, the researcher used an in-depth phenomenological method employing
      semi-structured questions and guided by a constructivist paradigm. Data were
      analyzed using qualitative analysis strategies (Bogdan & Biklen, 1992; Miles &
      Huberman, 1994). Results showed that concerns of beginning teachers of deaf and
      hard of hearing students are specific to service delivery models and geography.
      Participants provided specific recommendations for addressing the concerns of
      beginning teachers of deaf and hard of hearing students.

PMID- 15969222
TI  - Issues and trends in science education: the shortage of qualified science
      teachers.
AB  - Science teachers are leaving their profession. They feel overwhelmed by the
      expectations and scope of the job and isolated and unsupported in their
      classrooms. They also feel that expectations are unclear. The statistics on
      turnover among new teachers are startling. School administrators, science teacher
      leaders, and teacher education programs can do much more to promote better
      preparation of science teachers and to recruit new teachers into science
      teaching. In particular, the author focuses on relevant research and on
      recommendations for educational researchers and policymakers interested in
      improving and retaining qualified science teachers in classrooms.

PMID- 15969223
TI  - Deaf college students' attitudes toward racial/ethnic diversity, campus climate,
      and role models.
AB  - Deaf college students' attitudes toward a variety of issues related to
      racial/ethnic diversity were surveyed by contacting all racial/ethnic minority
      deaf students and a random sample of Caucasian deaf students attending the
      National Technical Institute for the Deaf (NTID), Rochester Institute of
      Technology; 38% completed the survey. Although racial/ethnic groups similarly
      perceived NTID's commitment and efforts related to diversity, they differed
      significantly on some items related to campus climate and role models.
      Furthermore, the racial/ethnic minority groups differed from each other in their
      perceptions of campus comfort level, racial conflict, friendship patterns, and
      availability of role models. Educational satisfaction was positively correlated
      with campus comfort level; both correlated negatively with perception of
      discrimination and racial conflict. Qualitative data analyses supported
      quantitative data analyses and provided rich detail that facilitated
      interpretation of deaf students' experiences related to racial/ethnic diversity.

PMID- 15969224
TI  - Sports and the deaf child.
AB  - The increasingly sedentary American lifestyle has resulted in a growing number of
      overweight and out-of-shape school-age children. Deaf children are not exempt
      from this trend, yet there is little evidence that public school programs for
      these children are doing anything to counter it. Much can be done to assist deaf
      students, not only in becoming more active movers but in gaining knowledge of
      opportunities and benefits associated with Deaf sport. The authors provide an
      argument for schools that expose deaf children to the role of sports in the Deaf
      community and for designing programs that will enable these children to become
      active participants in Deaf sport activities as athletes and organizers, or,
      later in life, when they no longer have the inclination or ability to compete, as
      spectators, with all the socialization benefits that form of involvement
      provides.

PMID- 15969225
TI  - Cross-cultural instrument translation: assessment, translation, and statistical
      applications.
AB  - This article has four major sections: (a) general issues of assessment; (b)
      assessment of ethnic-group members, including those who are deaf; (c) translation
      of assessment tools, emphasizing translation into American Sign Language (ASL);
      and (d) statistical applications for translated instruments. The purpose of the
      article is to provide insight into and guidelines for translating instruments
      into another language and using the results for practice or research purposes.
      The use of translated instruments with deaf individuals is highlighted. A
      protocol for translating a scale into ASL is offered. Statistical applications
      for examining internal consistency and component structure are discussed.
      Finally, implications for practice and research are addressed.

PMID- 15969226
TI  - [Pouchitis treatment by probiotics].
AB  - OBJECTIVES: The aim of the study was to review the principal effects of
      probiotics on pouchitis and identify their mechanisms of action. METHODS: The
      study was based on a review of all relevant studies published in the literature
      on the effects of probiotics in pouchitis and their possible mechanisms of
      action. RESULTS: Pouchitis is the major long-term complication after ileal pouch
      anal anstomosis for ulcerative colitis. The cause is still unknown but is likely
      to be multifactorial. An imbalance in the usual fecal flora was recently
      suggested. Most patients with symptoms of pouchitis respond promptly to
      antibiotics. However, 5-10% of them develop rapidly relapsing symptoms that
      required protacted therapy. Porbiotics are living microorganisms that ingested in
      adequate amounts exert beneficial effects. Promising results have been obtained
      with probiotics mainly in maintenance of remission of chronic pouchitis and also
      as induction of remission. CONCLUSION: These results suggest that restoring the
      microbial imbalance may offer an effective therapeutic alternative to patients
      with pouchitis.

PMID- 15969227
TI  - [Maternal and foetal prognostic during severe toxemia].
AB  - Severe gravidic toxemia gives heavy maternal and foetal morbidity and mortality.
      The purpose of our study is to loosen the factors of bad maternal and foetal
      prognostic. It's a retrospective study about 100 cases of severe and complicated
      gravidic toxemia repertorieted in the maternity of Military Hospital of Tunis.
      Maternal morbidity is dominated by the complications of hypertension and a blood
      disorders. We raised 4 cases of eclampsia, 9 cases of retro placental hematome
      and 5 cases of HELLP syndrome. We don't deplore any maternal death. Perinatal
      mortality is 28.8%. The rate of delay intra-uterine growth was 43.8% and the
      prematurity 65.9%. More toxemia appears early during pregnancy more maternal and
      foetal prognostic is compromised.

PMID- 15969228
TI  - [Duodeno-pancreatic trauma. About 14 cases].
AB  - Through a series of 14 cases brought over a period of 12 years, we realized a
      retrospective, analytical and descriptive study of these traumatisms. We aimed to
      release recommendations to improve their management. It was 2 women and 12 men,
      whom mean age was 24.4 years (extremes: 50 and 60 years), divided into 10
      pancreatic injuries, 2 duodenal injuries and 2 duodeno-pancreatic injuries.
      Etiology was dominated by traffic accidents 7 cases (50%). Trauma was closed in
      13 cases (92%). Associated lesions were present among 13 patients (92%). The
      traumatism appeared by an urgent surgical abdomen among 9 patients, secondarily
      in 3 cases, tardily in 2 cases: a case of deep suppuration 3 months after a
      traumatism treated into ambulatory and a case of persistent ascites after a past
      unperceived traumatism. Abdominal ultrasonography was made among 4 patients. It
      allowed diagnosing only a case. Scanner was made among 4 patients. It allowed
      diagnosing all the cases. Only a patient was treated medically, it was a post
      traumatic acute pancreatitis. Surgical treatment was made in 13 cases:
      conservative in 7 cases and radical in 6 cases. Follow-up was complicated in 11
      cases (78%) and non-complicated in 3 cases. Mortality rate was 7.1%.

PMID- 15969229
TI  - [Predictive factors of recurrence in Crohn's disease].
AB  - BACKGROUND AND AIMS: The aim of this study is to determine the factors associated
      with high risk of recurrence of Crohn disease. PATIENTS AND METHODS: During 12
      years period from January 1987 till December 1999, 98 patients treated for
      Crohn's disease were included in this study. The risk of recurrence was studied
      using the Kaplan-Meier method. The possible predictive factors of recurrence were
      studied using the LOGRANK test. RESULTS: During the follow-up period, 50 (66%)
      patients developed a recurrence of Crohn's disease. The factors associated with a
      high risk of recurrence of the diseases were female (p=0.03), long delay before
      the diagnosis of the disease (p=0.03) and the presence of extra-intestinal
      lesions (p=0.05). Concerning other factors such as the age, smoking, inflammatory
      syndrom and ano-perineal lesions, the study showed no relationship between these
      factors and the recurrence of the disease. CONCLUSION: This study showed that the
      group of patients treated for Crohn's disease and who have predictive factors of
      recurrence should have prophylactic medical treatment to prevent recurrence of
      the disease.

PMID- 15969230
TI  - [The managment of serious pregnant disease in the intensive care unit].
AB  - We report a retrospective study over a period of 4 years and half and bearing on
      59 patients that require an intensive care. The number of childbirth during this
      period was 22237 with 8.97% of Caesareans. The main obstetrical diseases was:
      gravidic toxaemia 75.5%, uterine inertia 7%, cardiopathy 5% of the cases. The
      reasons for the transfer were: eclamptic state in 27% of the cases, hemostasis
      disorder 22% of the cases, and acute pulmonary oedema 18.6% of the cases. Average
      duration of hospitalization was 3.18 days. Five cases of death were noted.

PMID- 15969231
TI  - [Leflunomide in the treatment of rheumatoid arthritis].
AB  - The aim of this study was to assess the effect and safety of leflunomide (LEF) in
      refractory RA and to review the literature on this subject. A one year
      prospective study was conducted on a group of patients (n:15). Mean duration
      disease was 6.46 years. Rhumatoid factor was present in 12 cases. Leflunomide was
      administered at a dos of 20mg/day following a loading dose of 100mg/day for three
      days. The efficacy of LEF was evaluated on clinical and biological parameters of
      RA evolutivity at one, 3, 6, 9 and 12 months. Our mean follow up period was about
      8 months (2 to 12 months). Good prognostic indicators of disease progression were
      observed with LEF at one month and later in eleven cases with a good safety. Non
      serious adverse events were observed with LEF. Our result confirm that LEF may
      present another therapeutic choice that is efficacious for the long term
      treatment of refractory RA. Nonetheless, these results must be evaluated on a
      larger series.

PMID- 15969232
TI  - [Acute myocardial infarction with normal coronary angiography: a 46-cases
      descriptive study].
AB  - This a retrospective study on 46 patients conducted over a 9-year period. These
      patients had an acute myocardial infarctus (AMI) confirmed wilth changes on the
      electrocardiogram and raised cardiac enzymes. However, the subsequent coronary
      angiography showed normal in all these patients. The purpose of our study is to
      assess epidemiologic, clinical, pronostic and therapeutic features of AMI with
      angiographically normal coronary arteries and compare the results obtained with
      those of AMI with coronary artery disease. AMI with angiographically normal
      coronary arteries is a first coronary event in young patients (mean age 47.7
      years) having few coronary risk factors (54.3% have only one risk factor) mainly
      smoking (73.9%). The anterior location is prevalent. The patients with AMI and
      angiographically normal coronary arteries have a better prognosis than those with
      coronary artery stenosis. Indeed, their left ventricular function is unaltered
      (mean ejection fraction 48.7%). Hypokinesis is the most frequent abnormality of
      wall motion noticed. The patients' post infarction course is bengin when the
      coronary arteries are angiographically normal. The incidence of hemodynamic
      complications and ischemic recurrences are lower than in AMI with coronary
      stenosis. The choice treatment remains fibrinolysis.

PMID- 15969233
TI  - [The place of MRI in the hepatic tumors].
AB  - MRI semeiology of hepatic tumors was assessed with a retrospective study of 132
      patients explored between May 1998 and December 2001. MR examinations were
      acquired with a one Tesla operating system. All images were acquired by a T2
      weighted fast spin echo MR and dynamic flash MR with Gadolinium. Hemangiomas
      demonstrate characteristic signs in most cases, as was described in the
      literature. However, adenoma, hepatocellular carcinoma and metastases have
      various and less specific features.

PMID- 15969234
TI  - [Evaluation of the antibiotics consumption in a Tunisian university hospital].
AB  - PURPOSE: To estimate the consumption of antibiotics in our hospital and to
      determine the points at which will be targeted the recommendations of good
      practice of antibiotherapy. PATIENTS AND METHODS: Our study is a one day
      prevalence study where antibiotic's prescriptions are analyzed by a group of 6
      doctors referents in antibiotherapy. RESULTS: During the study day, 443 patients
      were studied. Means age was 44.2 +/- 23.3 years (range: 1 and 102 years). 101
      infections were diagnosed in 48 patients (10.8%). 192 patients (43.3%) received
      antibiotics. Antibiotherapy was curative in 44% of cases. The most prescribed
      antibiotics were gentamicin (85.2 DDD/1000 patients), metronidazole (79 DDD/1000
      patients), and cefotaxime (73.9 DDD/1000 patients). According to the evaluation
      group, 30.7% of the antibiotic's prescription was considered unjustified. The
      antibioprophylaxis represents the category most often unjustified (49%). The
      molecules in which prescription was frequently considered unjustified are the
      ciprofloxacin (67%), the amoxicilline-clavulanate (40%) and the cefotaxime (40%).
      CONCLUSION: Our results suggest that an action of good practice should be
      targeted at the antibioprophylaxis and should concern especially molecules in
      which prescription was frequently unjustified.

PMID- 15969235
TI  - [Primary T-cell lymphoma of the pancreas in children].
AB  - Involvement of the gastrointestinal tract is frequently reported among the
      extranodal sites of non-Hodgkin's lymphoma, but primary lymphoma of the pancreas
      is very rare. We report the case of a 11-year-old boy explored for epigastric
      pain with fever leading to the diagnosis of high-grade primary non Hodgkin's T
      cell lymphoma, originating from pancreas. This pancreatic lesion is documented by
      sonography, CT and MRI. This patient died quickly with sever infection.

PMID- 15969236
TI  - [Posterior cerebral encephalopathy].
AB  - Posterior reversible encephalopathy (PRE) is a recent syndrome characterized by
      headache, vomiting, seizures, visual loss, altered mental status with or without
      motor or sensitive deficit. Neuroimaging demonstrates symmetrical posterior
      cortical and subcortical lesions. The aetiology remains uncertain but vascular
      hypotheses is the most retained. We report a case of a 21 year old man with
      posterior cerebral encephalopathy, the toxic hypo these remains the most
      probable.

PMID- 15969237
TI  - [Cerebellar liponeurocytoma. Case report].
AB  - The cerebellar liponeurocytoma is a rarely and recently described tumour. It may
      be distinguished on the basis of neuroimaging findings that demonstrate the areas
      of fat density. Complete surgical removal with postoperative radiation therapy is
      recommended. It has a relatively more favourable prognosis. We report the case of
      a 38-year-old woman without particular pathological antecedent with a few months
      history of headache and dizziness, aggravated since 2 days by signs of increased
      intracranial pressure and cerebellar dysfunction. The Computerized Tomography
      practiced in emergency showed a subtentorial space occupying mass, heterogeneous,
      exhibiting the attenuation values of fatty tissue, with hydrocephalus upstream.
      The patient has been operated. The histopathological and immunohistochemical
      studies concluded to a cerebellar liponeurocytoma.

PMID- 15969238
TI  - [Erythema elevatum diutinum. A clinicopathologic study of 5 cases].
AB  - Erythema elevatum diutinum is a rare condition of unknown etiology listed with
      cutaneous vasculitis or neutrophilic diseases. Medical records and
      histopathologic slides of 5 patients with erythema elevatum diutinum were studied
      to better understand the disease. Lesions were clinically characteristic. All
      biopsy specimens showed leucocytoclastic vasculitis. The most significant finding
      is the association of erythema elevatum diutinum whith seronegative rheumatoid
      arthritis.

PMID- 15969239
TI  - Evaluation of the effects of various gestagens on insulin sensitivity, using
      homeostatic model assessment, in postmenopausal women on hormone replacement
      therapy.
AB  - The objective of the present study was to compare the effects of various
      gestagens on insulin sensitivity in postmenopausal women on hormone replacement
      therapy (HRT). This prospective study enrolled 156 postmenopausal women who had
      menopausal status for at least 6 months. Group 1 was treated with 17 beta
      estradiol (E2; 2 mg) plus norethisterone acetate (NETA; 1 mg); Group 2 was given
      E2 (2 mg) plus medroxyprogesterone acetate (MPA; 2.5 mg); Group 3 was given E2 (2
      mg) plus dydrogesterone (DG; 10 mg); and Group 4 was given E2 (2 mg) plus
      micronized progesterone (MP; 100 mg). Group 5 was the surgical menopausal group
      and was given only E2 (2 mg) continuously. All 156 subjects completed the 3-month
      follow-up on the trial. The patients were analyzed by using homeostatic model
      assessment (HOMA) for insulin sensitivity before treatment and 3 months after
      treatment, comparing the effects of various HRT regimens on insulin sensitivity.
      No significant differences were found in the baseline characteristics of the
      patients (p > 0.05). There were no significant differences in mean values of HOMA
      before HRT among the five groups (p > 0.05). There were statistically significant
      differences in mean values of HOMA only in Group 1 (E2 + NETA) and Group 3 (E2 +
      DG) after HRT (p > 0.05). E2 + NETA and E2 + DG were found to improve insulin
      sensitivity in postmenopausal women after 3 months of treatment, whereas E2 +
      MPA, E2 + MP and E2 only did not show such an effect in postmenopausal women.

PMID- 15969240
TI  - Effects of estriol on proliferative activity and expression of insulin-like
      growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like
      osteosarcoma cells.
AB  - The present study was undertaken to elucidate whether estriol (E3) affects the
      proliferative activity and the expression of insulin-like growth factor-I (IGF-I)
      mRNA and IGF-I receptor (IGF-IR) mRNA in cultured human osteoblast-like
      osteosarcoma cells (HOS TE85). In this study, the effects of E3 on cultured HOS
      TE85 cells were compared with those of 17 beta-estradiol (E2). HOS TE85 cells
      were subcultured in phenol red-free Dulbecco's modified Eagle's medium
      supplemented with 10% fetal bovine serum for 72 h and then stepped down to serum
      free conditions for an additional 72 h in the absence or presence of E3 (3.52 x
      10(-9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l).
      Treatment with either E3 (3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(
      8) mol/l) resulted in an increase in the number of cultured HOS TE85 cells and
      their uptake of bromodeoxyuridine. Northern blot hybridization with a IGF-I cDNA
      probe revealed that RNA prepared from cultured HOS TE85 cells contained IGF-I
      mRNA transcripts of 1.8, 4.4 and 7.5 kb. Treatment with either E3 (3.52 x 10(-9),
      3.52 x 10(-8), 3.52 x 10(-7) mol/l) or E2 (3.67 x 10(-8) mol/l) resulted in
      increased expression of the three mRNA transcripts relative tot hose in untreated
      control cultures. Semi-quantitative, reverse transcription polymerase chain
      reaction analysis showed that the 440-bp IGF-IR mRNA transcript was present in
      HOS TE85 cells and that treatment with either E3 or E2 did not affect the IGF
      IRmRNA expression in these cells. These results demonstrate that E3 (3.52 x 10(
      9), 3.52 x 10(-8), 3.52 x 10(-7) mol/l) exerts profound effects on the
      proliferative potential of cultured HOS TE85 cells, compatible with that of E2
      (3.67 x 10(-8) mol/l), through the induction of IGF-I mRNA expression without
      affecting IGF-IR mRNA expression in these cells.

PMID- 15969241
TI  - Alternatives to estrogen to manage hot flushes.
AB  - Hot flushes are probably the most common symptom resulting in medical
      consultation in relation to the menopause and, when severe, they can affect quite
      dramatically women's quality of life. Hormone (estrogen) replacement therapy
      (HRT) is the most effective treatment for this symptom and in the ideal setting
      of clinical trials, under optimal selection of patients and compliance, it
      reduces hot flushes by about 70-80%. Recently, however, a series of 'scares' has
      had large resonance in the lay press about possible adverse effects of HRT. These
      have undermined both doctors' and women's confidence in the use of these
      compounds. This has been witnessed by the recent fall in HRT sales. A number of
      compounds, both pharmacological and herbal in origin, have been used for the
      treatment of neurovegetative symptoms in menopausal women. The present article
      critically reviews evidence of the efficacy of some of the most commonly used
      compounds and assesses their effect in relation to that of HRT.

PMID- 15969242
TI  - Familial hypopituitarism associated with mosaic form of Turner syndrome.
AB  - We present herein an unusual coincidence of familial hypopituitarism associated
      with a mosaic form of Turner syndrome in two adult sisters (51 and 43 years old).
      Both patients had hypopituitarism diagnosed in childhood. They have never been
      administered growth hormone, and remained short in stature. They were not given
      long-term estrogen-progestin treatment, despite lack of menstruation. Early in
      childhood both received thyroid hormone substitution. Pituitary imaging revealed
      pituitary hypoplasia with partial empty sella in one sister, and pituitary
      hypoplasia in the other. Very recently, during endocrinological evaluation, they
      were diagnosed with a mosaic form of Turner syndrome, additionally to their
      hypopituitarism. In this paper, we place special emphasis on the results of
      hormonal analyses and discuss the differential diagnosis.

PMID- 15969243
TI  - Effect of human hydrosalpinx fluid on the development of mouse embryos and role
      of the concentration of growth factors in culture medium with and without
      hydrosalpinx fluid.
AB  - The aim of this study was to investigate the effect of human hydrosalpinx fluid
      (HF) on the development and blastulation of mouse embryos and the role of the
      concentration of growth factors in culture medium with and without HF. In total,
      2100 mouse embryos were cultured. Female mice were induced to superovulate and
      then mated with males. Two-cell-stage embryos were recovered from the oviduct and
      cultured in Ham's F-10 medium with bovine serum albumin and HF. Epidermal growth
      factor (EGF) and insulin-like growth factor-I (IGF-I) were analyzed by
      quantitative enzyme immunoassay. Mean blastulation index of 1.11, 0.97 and 0.98
      was found at HF concentration of 5%, 20% and 30%, respectively (p = 0.8). The
      mean value of EGF in the control culture medium without HF was 11.2 pg/ml, which
      was statistically significantly different from that in culture medium containing
      HF (p < 0.001). The mean value of IGF-I in the control group without HF was 1.30
      pg/ml and was not statistically significantly different from that in culture
      medium containing HF. Development of the two-cell-stage embryos was not affected
      at low (< 30%) HF concentrations. In conclusion, the present study demonstrates
      that even apparently normal blastulation is affected by any concentration of HF
      because of low embryonic EGF.

PMID- 15969244
TI  - Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study
      versus low-dose transdermal estradiol.
AB  - OBJECTIVE: To investigate, in a randomized clinical study, the efficacy of an
      isopropanolic aqueous extract of Cimicifuga racemosa (CR) on climacteric
      complaints in comparison with low-dose transdermal estradiol (TTSE2). Hormonal
      parameters, lipid profile and endometrial thickness were also evaluated. METHODS:
      Sixty-four postmenopausal women were enrolled and over the course of 3 months
      filled in a diary recording the number of hot flushes per day. Other climacteric
      symptoms (vasomotor and urogenital symptoms) as well as anxiety and depression,
      were evaluated at baseline and after 3 months. Gonadotropins (follicle
      stimulating hormone (FSH), luetinizing hormone (LH)), prolactin (PRL), 17 beta
      estradiol (17beta-E2) and cortisol, lipid profile (total cholesterol high-density
      lipoprotein (HDL)/low-density lipoprotein (LDL)-cholesterol, triglycerides, liver
      function (glutamic-oxalacetic transaminase, glutamic-pyruvic transaminase) and
      endometrial thickness were measured. Patients were randomly allocated to receive,
      for 3 months, either 40 mg isopropanolic aqueous CR extract daily or 25 microg
      TTSE2 every 7 days plus dihydrogesterone 10 mg/day for the last 12 days of the 3
      month estradiol treatment. RESULTS: Both CR and low-dose TTSE2 significantly
      reduced the number of hot flushes per day (p < 0.001) and vasomotor symptoms (p <
      0.001), starting at the first month of treatment. Such a positive effect was
      maintained throughout the 3 months of observation, without any significant
      difference between the two treatments. An identical effect was evident also for
      both anxiety (p < 0.001) and depression (p < 0.001) which were significantly
      reduced following 3 months of both CR and low-dose TTSE2. Total cholesterol was
      unchanged by CR treatment but significantly (p < 0.033) reduced by 3 months of
      low-dose TTSE2. A slight but significant increase of HDL-cholesterol (p < 0.04)
      was found only in women treated with CR, while LDL-cholesterol levels were
      significantly lowered by 3 months of both CR (p < 0.003) and low dose TTSE2 (p <
      0.002). Triglycerides were not affected by both treatments, nor was liver
      function. FSH, LH and cortisol were not significantly affected after the 3-month
      treatment, while PRL (p < 0.005) and 17 beta-E2 (p < 0.001) were increased
      slightly only by low-dose TTSE2. Endometrial thickness was not affected by either
      CR or low-dose TTSE2. CONCLUSIONS: CR (40 mg/day) may be a valid alternative to
      low-dose TTSE2 in the management of climacteric complaints in those women who
      cannot be treated with or just refuse conventional strategies.

PMID- 15969245
TI  - Human races and pharmacogenomics of effective bone treatments.
AB  - Osteoporosis and its complications represent one of the most important causes of
      morbidity and mortality around the world. Moreover, its management presents an
      important economic problem. Although osteoporosis is a worldwide health problem,
      there are many differences in ethnic groups regarding disease morbidity and drug
      treatment efficacy. This review analyzed clinical response data of two major
      osteoporotic treatments (vitamin D and estrogens) regarding four major human
      races (Asian, Caucasian, Hispanic and Negroid). From clinical studies, Asians
      seem to be more vitamin-D-sensitive while Caucasians appear more estrogen
      sensitive than other human races. Different drug responses may be related to
      allelic variants in their signaling genes such as those for the vitamin D
      receptor (VDR) and estrogen receptor-alpha (ER alpha). Some polymorphisms of VDR
      and ER alpha loci appear to be genetic determinants of osteoporotic risk: ApaI
      BsmI-TaqI, FokI variants and poly(A) repeats in VDR; PvuII-XbaI variants and (TA)
      repeats in ER alpha. Also, because of specific ethnic allele distributions, these
      VDR and ER alpha polymorphisms may be involved in race differences of
      osteoporosis treatment responses. Future studies and preventive strategies for
      the management of osteoporosis need to take into account these racial and genetic
      factors.

PMID- 15969246
TI  - Is there a role for a random measurement of 24-hour urine calcium excretion in
      the determination of calcium supplementation in osteoporotic postmenopausal women
      using alendronate?
AB  - The article addresses the clinical query whether a casual determination of 24
      hour urinary calcium excretion by the end of first-year treatment with
      alendronate in osteoporotic postmenopausal women correlates with the change in
      bone mineral density achieved during that year. The study included 2 arms: a
      prospective arm (n = 31) with women on long-term hormone replacement therapy were
      followed for 1 year after addition of alendronate (10 mg/daily); a retrospective
      arm (n = 33) with women using alendronate for 1 year. Bone mineral density and
      urine deoxypyridinoline were measured at baseline and 1 year, 24-hour urine
      calcium was obtained at 1 year. All patients used supplemental calcium, but the
      exact intake values were not determined. The results demonstrated no correlation
      between the annual increase in both spine and femur bone density and urinary
      calcium. Assuming that urinary calcium correlates with calcium intake and
      absorption, a casual measurement of urinary calcium excretion seems irrelevant
      for the titration of optimal calcium supplementation in this clinical setup.

PMID- 15969247
TI  - Algorithm for treatment of premenstrual syndromes (PMS): experts' recommendations
      and limitations.
AB  - The number of women who seek treatment for Premenstrual Syndromes (PMS) is
      continually increasing. To meet their needs there are many treatment modalities
      that have been introduced to clinical practice. In order to assist the clinician
      in choosing treatment for his/her patients, treatment recommendations by experts
      in the field are not only available but they may also be prioritized and
      sequenced as treatment algorithm. Such an algorithm for treatment of women with
      PMS is presented here. The algorithm is the author's summary and common
      denominator of several experts' consensus building group processes. The strengths
      as well as shortcomings of the experts' opinions processes are discussed.
      Substantial clinically-relevant research and assessments are still needed.

PMID- 15969248
TI  - Impact of blood pressure variability on cardiovascular events in elderly patients
      with hypertension.
AB  - Blood pressure variability is one of the characteristic features of hypertension
      in the elderly. However, its clinical significance remains to be determined. We
      therefore examined the impact of blood pressure variability on the development of
      cardiovascular events in elderly hypertensive patients. A total of 106
      consecutive hypertensive patients aged more than 60 years old (mean age, 73.9 +/-
      8.1 years old; male, 54%), all of whom underwent 24-h ambulatory blood pressure
      monitoring, were followed up (median, 34 months; range, 3-60 months). During the
      follow-up period, 39 cardiovascular events were observed, including 14 cases of
      cerebral infarction and 7 cases of acute myocardial infarction. The coefficient
      of variation (CV) of 24-h systolic blood pressure (SBP) values was used as an
      index of blood pressure variability. The patients showed a mean CV value of
      10.6%, and were divided into two groups according to this mean value as a cut-off
      point: a high CV group (n = 46) and a low CV group (n = 60). Although baseline
      clinical characteristics were similar in the two groups, Kaplan-Meier plots for
      event-free survival revealed that the rate of cardiovascular events was
      significantly higher in high CV group than in low CV group (p < 0.05). Cox's
      proportional hazards analysis showed that increased blood pressure variability (a
      high CV value of 24-h SBP) was an independent predictive variable for
      cardiovascular events. The CV value of daytime SBP and the SD value of both 24-h
      SBP and daytime SBP also had positive correlations with the onset of
      cardiovascular events. These results suggest that increased blood pressure
      variability may be an independent risk factor for cardiovascular events in
      elderly hypertensive patients.

PMID- 15969249
TI  - Higher brachial-ankle pulse wave velocity is associated with more advanced
      carotid atherosclerosis in end-stage renal disease.
AB  - Brachial-ankle pulse wave velocity is a new measure of arterial stiffness. We
      examined whether higher brachial-ankle pulse wave velocity is associated with
      more advanced carotid atherosclerosis and left ventricular hypertrophy in
      patients with end-stage renal disease, and whether this effect would be mediated
      by the influence of wave reflection on central arterial pressure. In 68 patients
      with end stage renal disease, we examined blood pressures, brachial-ankle pulse
      wave velocity and the augmentation index of the left common carotid artery, a
      measure of the impact of wave reflection on the systolic peak in central
      arteries. The degree of carotid atherosclerosis was quantified by a plaque score
      and maximum intimal-medial thickness. Echocardiography was used to determine the
      left ventricular mass index. In simple regression analysis, brachial-ankle pulse
      wave velocity was correlated with both plaque score and maximum intimal-medial
      thickness (r = 0.420, p < 0.001 and r = 0.452, p < 0.0005, respectively) but not
      with left ventricular mass index. Multiple regression analysis was performed with
      the plaque score or maximum intimal-medial thickness as the dependent variable
      and brachial-ankle pulse wave velocity and known clinical risk factors as the
      independent variables. The brachial-ankle pulse wave velocity was an independent
      risk factor for both plaque score (beta = 0.006, p = 0.004) and maximum intimal
      medial thickness (beta = 0.008, p = 0.04). Independent risk factors for left
      ventricular mass index were left ventricular diastolic dimension (beta = 3.509, p
      = 0.000007) and augmentation index (beta = 0.580, p = 0.04). The brachial-ankle
      pulse wave velocity was unrelated to augmentation index in patients with end
      stage renal disease. In conclusion, higher brachial-ankle pulse wave velocity was
      found to be a risk factor for carotid atherosclerosis in patients with end-stage
      renal disease; this effect was independent of the influence of wave reflection on
      central arterial pressure. The brachial-ankle pulse wave velocity was unrelated
      to left ventricular structure.

PMID- 15969250
TI  - Altered aortic properties in elderly orthostatic hypertension.
AB  - To investigate the impact of arterial properties on orthostatic blood pressure
      (BP) dysregulation in older hypertensives, orthostatic BP dysregulation, a common
      phenomenon in elderly hypertensives, is associated with target organ damage and
      falls. However, the mechanism of orthostatic BP dysregulation remains unclear.
      The pulse wave velocity (PWV), related arterial stiffness, and the augmentation
      index (AI), a measure of arterial wave reflection, were measured in 365 older
      hypertensives. We classified the study patients into an orthostatic hypertension
      (OHT) group with orthostatic increase of systolic BP (SBP) of > or = 220 mmHg (n
      = 27) and an orthostatic normotension (ONT) group with an orthostatic increase of
      SBP of < 20 mmHg and orthostatic SBP decrease of < 20 mmHg (n = 338). Orthostatic
      AI was significantly greater in the OHT group than in the ONT group (OHT: 6.5 +/-
      12% vs. ONT: -5.6 +/- 12%, p < 0.001), while supine AI and supine and orthostatic
      pulse rate were comparable between the two groups. There was no significant
      difference in the PWV between the OHT and ONT groups. Orthostatic hypertension
      was affected by altered aortic properties and associated with augmented wave
      reflection of arterial pressure.

PMID- 15969251
TI  - Relationship between impaired aldosterone response to adrenocorticotropic hormone
      and prevalence of hemodialysis in type 2 diabetic patients without azotemia.
AB  - The present prospective observational study was designed to assess the prevalence
      of hemodialysis in type 2 diabetic patients with an impairment of plasma
      aldosterone responsiveness to adrenocorticotropic hormone (ACTH). Sixty seven
      patients (43 men and 24 women) were selected. The inclusion criteria were age <
      65 years; presence of normoalbuminemia (serum albumin > 3.6 g/dl); and absence of
      azotemia (serum creatinine < or = 1.2 mg/dl in males, and < or = 1.0 mg/dl in
      females). Soluble alpha(1-24)-ACTH was injected intramuscularly in a single dose
      of 0.25 mg after overnight recumbency. The area under the aldosterone curve
      (aldosterone AUC) was calculated. The diabetic patients were divided into two
      groups according to the levels of aldosterone AUC. Patients with an aldosterone
      AUC in the range of 0-381 were considered poor responders (n = 31) and those with
      an AUC of 397-1,007 were considered good responders (n = 36). The follow-up was
      performed during a 144-month period. The end point of the study was the
      introduction of hemodialysis. A total of 14 patients (12 poor responders and 2
      good responders; p < 0.001) were introduced to hemodialysis. The prevalence of
      hemodialysis in the poor responders (5.74 per 100 patient-years) was
      significantly higher (p < 0.001, log-rank test) than that in the good responders
      (0.68 per 100 patient-years). One possible explanation is that an inappropriate
      level of salt intake relative to the impaired plasma aldosterone control may have
      contributed to the high prevalence of risks and hemodialysis in the poor
      responders.

PMID- 15969252
TI  - Hypertension is the most common component of metabolic syndrome and the greatest
      contributor to carotid arteriosclerosis in apparently healthy Japanese
      individuals.
AB  - The cluster of metabolic and hemodynamic risk factors known as metabolic syndrome
      is known to be a risk factor for ischemic cardiovascular diseases and stroke. By
      analyzing the cross-sectional data from 8,144 individuals (age 19-88 years) who
      underwent general health screening, we have investigated the prevalence of
      metabolic syndrome, as diagnosed by modified-National Cholesterol Education
      Program (NCEP) criteria corresponding to the following five categories:
      triglycerides > or = 150 mg/dl; high density lipoprotein (HDL)-cholesterol < 40
      mg/dl in men or < 50 mg/dl in women; fasting plasma glucose > or = 110 mg/dl;
      systolic/diastolic blood pressure > or = 130/85 mmHg; and body mass index > 25
      kg/m2. We found that the prevalence of metabolic syndrome was 19% in men and 7%
      in women. After adjustment for age, metabolic syndrome was found to be
      significantly more prevalent in men than in women, with an odds ratio of 3.08
      (95% confidence interval [CI] 2.62-3.61, p < 0.0001). Among the five
      metabolic/hemodynamic risk factor components, hypertension was observed most
      frequently in individuals with metabolic syndrome, at 85% in men and 87% in
      women. In addition, multivariate logistic regression analysis adjusted for age,
      sex, serum total cholesterol levels, and smoking status showed that hypertension
      possessed the greatest odds ratio (1.43, 95% CI 1.27-1.60) for carotid plaque
      among the metabolic/hemodynamic risk factors. These data emphasize the importance
      of controlling blood pressure for reducing the risk of both metabolic syndrome
      and carotid arteriosclerosis in apparently healthy individuals.

PMID- 15969253
TI  - Single nucleotide polymorphisms in the interleukin-6 gene associated with blood
      pressure and atherosclerosis in a Japanese general population.
AB  - It is known that increased plasma levels of inflammatory markers, such as
      interleukin-6 (IL-6), are associated with atherosclerosis and myocardial
      infarction. The aim of this study was to reveal the contribution of the single
      nucleotide polymorphisms (SNPs) of the IL-6 gene on the blood pressure regulation
      and progression of atherosclerosis in a general Japanese population. In order to
      evaluate the potential implications of genetic variability of the IL-6 gene, we
      explored eight SNPs by direct sequencing for the entire coding region and the
      promoter region in the IL-6 gene and genotyped two SNPs, -636G > C in the
      promoter region and 1691C > G in intron 3, for a total of 2,421 Japanese subjects
      (1,162 men and 1,259 women). As a consequence, -636 G > C was significantly
      associated with systolic blood pressure (SBP) and carotid intima-media thickness
      (IMT) in women, and 1691C > G showed a relationship with SBP and carotid IMT in
      men after adjustment for all confounding factors. Although neither SNP had a
      significant correlation to the prevalence of hypertension, the haplotype
      frequency analysis indicated that the number of hypertensive men with a G allele
      at both -636 and 1691 was significantly greater than the number of
      nonhypertensive men with this combination. Thus, these two SNPs in the promoter
      region and intron 3 of the IL-6 gene might play a role in the blood pressure
      regulation and progression of atherosclerosis in the Japanese.

PMID- 15969254
TI  - Hemodynamic influences of losartan on the brain in hypertensive patients.
AB  - The effects of angiotensin II receptor blockers on cerebral hemodynamics in
      humans have not been well elucidated. The present study evaluated the effects of
      losartan on cerebral hemodynamics in hypertensive patients using positron
      emission tomography. Ten patients with essential hypertension (mean age, 60.8
      years) were examined. In each patient, regional cerebral blood flow was measured
      by [O-15] labeled water positron emission tomography before and after the oral
      administration of losartan for 8 to 23 weeks. In 8 patients, the baseline
      regional cerebral blood flow measurement was followed by 1,000 mg of
      acetazolamide challenge to measure the cerebral perfusion reserve. Systemic blood
      pressures before and after treatment were 153.8 +/- 10.8/96.0 +/- 6.5 mmHg
      (systolic mean +/- SD/diastolic mean +/- SD) and 133.4 +/- 11.2/83.6 +/- 6.5
      mmHg, respectively; this difference was significant. The baseline global cerebral
      blood flow values before and after treatment were 38.4 +/- 6.9 ml/min/100 g and
      38.2 +/- 8.2 ml/min/100 g, respectively; this difference was not significant. The
      results of the global cerebral blood flow response to the acetazolamide
      challenges were not statistically different before and after treatment. A
      regional analysis showed no statistical difference in regional cerebral blood
      flow or cerebral perfusion reserve throughout the brain before and after
      treatment. Losartan's effect on reducing the blood pressure did not affect either
      the baseline regional cerebral blood flow or the cerebral perfusion reserve in
      patients with mild to moderate hypertension. The inclusion of losartan in anti
      hypertensive regimens could be advantageous for cerebral circulation in patients
      with essential hypertension.

PMID- 15969255
TI  - Usefulness of serum adiponectin level as a diagnostic marker of metabolic
      syndrome in obese Japanese children.
AB  - This study aimed 1) to investigate the relationship between serum adiponectin
      levels and metabolic disorders and 2) to clarify the usefulness of serum
      adiponectin level as a diagnostic marker of metabolic syndrome in obese Japanese
      children. One hundred obese boys aged 8 to 13 years were examined. Serum
      adiponectin levels were measured by radioimmunoassay using a commercial kit.
      Abdominal fat thickness (maximum preperitoneal fat thickness: P(max); minimum
      subcutaneous fat thickness: S(min)) was measured by ultrasonography. The
      relationships between adiponectin and clinical characteristics were analyzed by
      simple regression. The relationships between anthropometric measurements and
      metabolic disorders were analyzed among three groups divided according to
      adiponectin percentile. The prevalence of metabolic syndrome was also analyzed,
      with metabolic syndrome defined as the presence of three or more complications of
      obesity. The criteria for metabolic syndrome by adiponectin were subjected to a
      receiver operating characteristic (ROC) analysis. Body weight, waist
      circumference, P(max), alanine aminotransferase and fasting serum insulin were
      all inversely correlated with adiponectin. There were significant differences in
      the prevalence of severe obesity, the accumulation of visceral adipose tissue,
      hyperinsulinemia, high serum low density lipoprotein-cholesterol, the number of
      complications of obesity and the prevalence of metabolic syndrome among the three
      groups. The area under the ROC curve for adiponectin was 0.672 +/- 0.055 and the
      cut-off value was 6.65 microg/ml. Hypoadiponectinemia was associated with
      visceral fat accumulation and metabolic syndrome in obese Japanese boys.
      Evaluation of adiponectin might contribute to an early intervention for obese
      children with metabolic syndrome.

PMID- 15969256
TI  - Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor
      and fibrinolytic responses induced by bradykinin.
AB  - Endothelium plays a key role in the regulation of not only vascular tone but also
      thrombosis and fibrinolysis. Brachial flow-mediated vasodilation (FMD) provides a
      noninvasive method of assessing coronary endothelial dysfunction. However, no
      data are available on the relationship between brachial FMD and coronary
      fibrinolytic activity. Thus, we examined the relationship between brachial FMD
      and coronary vasomotor and fibrinolytic function. Brachial FMD by reactive
      hyperemia was defined as a change in diameter relative to the baseline as
      measured using high-resolution ultrasound. Coronary blood flow (CBF) responses to
      bradykinin (BK) were analyzed using Doppler flow velocity measurement. Coronary
      release of tissue-type plasminogen activator (tPA) antigen was determined as the
      transcardiac tPA gradient x [CBF x (100 - hematocrity 100)]. In 77 patients with
      normal coronary arteries, BK caused dose-dependent increases in CBF, transcardiac
      tPA gradient, and coronary tPA release. Among them, brachial FMD, the BK-induced
      CBF increase, and the coronary tPA release induced by BK in 14 diabetic subjects
      were lower than those in 63 non-diabetic subjects (p < 0.05, respectively).
      Brachial FMD correlated with the CBF increase, transcardiac tPA gradient (0.2
      microg/min: r = 0.25; 0.6 microg/min: r = 0.43; 2.0 microg/min: r = 0.34; p <
      0.05, respectively), and coronary tPA release (0.2 microg/min: r = 0.24; 0.6
      microg/min: r = 0.44; 2.0 microg/min: r = 0.32; p < 0.05, respectively) in
      response to BK. Brachial FMD correlated significantly with coronary endothelial
      function and fibrinolytic activity in response to BK. Type 2 diabetes impaired
      coronary and brachial endothelium-dependent vasodilation and coronary
      fibrinolytic activity.

PMID- 15969257
TI  - Angiotensin II type 1 receptor antagonist and angiotensin-converting enzyme
      inhibitor altered the activation of Cu/Zn-containing superoxide dismutase in the
      heart of stroke-prone spontaneously hypertensive rats.
AB  - Although angiotensin II type 1 (AT1) receptor antagonists and angiotensin
      converting enzyme (ACE) inhibitors are known to reduce both reactive oxygen
      species (ROS) generated by activated NAD(P)H oxidase and vascular remodeling in
      hypertension, the effects of AT1 receptor antagonists or ACE inhibitors on ROS
      scavenging enzymes remain unclear. We hypothesized that AT1 receptor antagonists
      or ACE inhibitors may modulate vascular remodeling via superoxide dismutase (SOD)
      in hypertension. Male stroke-prone spontaneously hypertensive rats (SHRSP) were
      treated for 6 weeks with a vehicle, an AT1 receptor antagonist (E4177; 30
      mg/kg/day), or an ACE inhibitor (cilazapril; 10 mg/kg/day). We evaluated protein
      expression using immunoblots, determined SOD activities with a spectrophotometric
      assay, and measured NAD(P)H oxidase activity by a luminescence assay. The two
      drugs showed equipotent effects on blood pressure, left ventricular hypertrophy
      and fibrosis, and endothelial NO synthase in the SHRSP hearts. The wall-to-lumen
      ratio of the intramyocardial arteries and the NAD(P)H oxidase essential subunit
      p22(phox) and its activity were significantly reduced, whereas Cu/Zu-containing
      SOD (Cu/ZnSOD) expression and activity were significantly increased in the SHRSP
      hearts. Furthermore, E4177 reduced vascular remodeling more than did cilazapril
      not only by reducing p22(phox) expression and NAD(P)H oxidase activity but also
      by upregulating the Cu/ ZnSOD expression and its activity in the SHRSP hearts.
      Thus, both the AT1 receptor antagonist and the ACE inhibitor inhibited vascular
      remodeling and reduced ROS in SHRSP via not only a reduction in NAD(P)H oxidase
      but also an upregulation of Cu/ZnSOD.

PMID- 15969258
TI  - Different effects on inhibition of cardiac hypertrophy in spontaneously
      hypertensive rats by monotherapy and combination therapy of adrenergic receptor
      antagonists and/or the angiotensin II type 1 receptor blocker under comparable
      blood pressure reduction.
AB  - To confirm that alpha1, beta adrenoceptor antagonists and angiotensin II type 1
      receptor blockers (ARBs) have different abilities to attenuate progressive
      cardiac hypertrophy despite their comparable lowering of blood pressure, we
      compared the effect of these agents alone or in combination on hypertensive
      cardiac hypertrophy. Eight-week-old spontaneously hypertensive rats (SHR) were
      divided into 7 groups. Single administration of doxazosin, atenolol, or losartan,
      or half-dose combinations of these drugs were given orally for 6 weeks. The
      control group did not receive any drugs. The heart weight-to-body weight ratio
      (HW/BW), left ventricular mass index (LVMI), plasma brain natriuretic peptide
      (BNP) and left ventricular BNP mRNA expression were measured after 6-week
      administration. Blood pressure did not differ among the drug-treated groups, all
      of which showed lower blood pressure than the control group. The HW/BW and LVMI
      of the drug-treated groups, except the doxazosin group, were lower than in the
      control group. Moreover, the LVMI values of the groups receiving losartan were
      significantly lower than those in the groups without losartan (p < 0.05). Plasma
      BNP of the drug-treated groups was lower than that in the control group (p <
      0.05). The left ventricular BNP mRNA expression of the drug-treated groups,
      except the doxazosin group, was lower than that in the control group. The
      atenolol group showed a higher level of BNP mRNA than the groups receiving
      losartan monotherapy or combination therapies (p < 0.05). In conclusion, the ARB
      had the strongest attenuating effect on the development of hypertensive cardiac
      hypertrophy, and the alpha1 and beta adrenergic receptor blockers were more
      effective in combination than as monotherapies in SHR.

PMID- 15969259
TI  - Thrombotic microangiopathy in malignant hypertension and hemolytic uremic
      syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate
      one from the other?
AB  - Patients with malignant hypertension sometimes exhibit microangiopathic hemolytic
      anemia/thrombocytopenia known as thrombotic microangiopathy (TMA). On the other
      hand, severe hypertension is sometimes associated with hemolytic uremic syndrome
      (HUS)/thrombotic thrombocytopenic purpura (TTP). Because the clinical features of
      the two entities overlap significantly, it is sometimes difficult to distinguish
      one from the other. However, such differentiation is indispensable, since early
      performance of plasmapheresis is critical in HUS/TTP. It has been suggested that
      severe thrombocytopenia is one of the most useful differential points in
      diagnosing HUS/TTP from malignant hypertension caused by other etiologies. Early
      performance of plasmapheresis can be justified in the presence of both TMA and
      thrombocytopenia. However, thrombocytopenia can be seen in the cases with
      malignant hypertension from etiologies other than HUS/TTP, and in these
      particular cases, plasmapheresis is useless and can be harmful. Recently, the
      plasma level of ADAMTS13 (a disintegrin and metalloprotease domain, with
      thrombospondin type 1 motif 13), which is a von Willebrand Factor cleaving
      protease, has been shown to be very low in familial or some of the sporadic cases
      of TTP, and a low level of ADAMTS13 is very specific to TTP. Some reports have
      shown that patients with a very low plasma level of ADAMTS13 respond very well to
      plasmapheresis. We recently experienced two cases with TMA. Although both of our
      patients had severe hypertension with TMA, different therapeutic strategies
      ameliorated their illness: symptomatic treatment was effective in case 1, which
      showed normal ADAMTS13 activity, whereas plasma infusion was necessary to save
      case 2, which showed low ADAMTS13 activity. Thus, patients with a low level of
      ADAMTS13 activity might respond well to plasmapheresis or plasma infusion. When
      presented with patients with severe hypertension and thrombotic microangiopathy,
      ADAMTS13 activity may prove to be a promising adjunctive tool in differentiating
      TTP from TMA due to other etiologies, but in the meantime, we should make the
      choice of whether or not to perform plasmapheresis based on the degree of
      thrombocytopenia.

PMID- 15969260
TI  - [Harmonization for mesoamerican nutrient-based recommendations: regional
      unification or national specification?].
AB  - Mesoamerica, the area we focus for this paper, is a section of Latin America that
      extends from Central Mexico to Panama. The deliberations of international
      committees are the primary bases for their nutrient-based recommendations. To a
      smaller extent, the unique particularities of the bioavailability for one or
      another nutrient have been considered. The nutrient recommendations throughout
      the region are "relatively" uniform and mutually consistent with respect to:
      iron, iodine and most of the B-complex vitamins. discrepancies exist among the
      various sets of recommendations for other nutrients. A valid basis of
      harmonization would not be unification of recommendations across all
      nationalities, but rather assuring a consistency in the nutrient profile that is
      recommended provides the nutrient exposures and/or fills the body's reserves as
      best suits the goals of survival, growth, well-being and function within the
      ecological niche of the population. That the recommendations for nutrients must
      be satisfied from foods, foods that are accessible and culturally acceptable, and
      that approximate the parallel demands of food-based dietary guidelines, add
      additional constraints onto the process of enunciating the former.

PMID- 15969261
TI  - [Efficacy of a national program to promote breast feeding: Chile 1993-2002].
AB  - Promotion of breast feeding is a priority in Chilean health's policies. The aim
      of the study was to evaluate the tendency of breastfeeding (exclusive, continued,
      partial), in children less than 18 months old, controlled in the Chilean public
      health system, based in four national surveys. Through a 24 h food intake recall
      (breastfeeding, water, juice, infant formula, solids) food patterns were explored
      every 3 years, as well as maternal participation in jobs located away from home.
      the sample consisted of approximately 10 thousand children, less than 18 months
      old of the 28 health services throughout the country. The prevalence of children
      with exclusive breastfeeding, predominant (breastfeeding, water or juice),
      complemented (breastfeeding plus solids) or any other way of feeding for each
      month of age in each survey, and changes in period studied, was determined.
      Between 1993 and 2002, exclusive breastfeeding for 6 months increased from 16 to
      43.1% (p<0.001) and predominant breastfeeding from 25.4 to 57.4%. at the same
      time, complemented breastfeeding at 12 months increased from 10.7 to 21.3%, and
      partial or complemented breastfeeding in 12 to 18 month old children went from
      24.1 to 46.7%. Maternal work located away from home was inversely associated with
      the prevalence of exclusive and complemented breastfeeding during the first year
      (p<0.001). There has been a significant increase of maternal breastfeeding in the
      period analyzed. The negative effects of maternal labor on breastfeeding suggests
      to explore more effective forms of social support to the working mother.

PMID- 15969262
TI  - [The green tea, a good choice for cardiovascular disease prevention?].
AB  - Tea (Camellia sinensis) has been used for centuries as a medical drink. Around
      two-thirds of the world's population drink tea. It is originated from southern
      China and entensive cultivated in Asia and in central African countries. Tea can
      be grouped into three main types, black, oolong, and green tea. Green tea is not
      fermented and is a major beverage consumed in Asian countries. Green tea is
      produced from freshly harvest leaves of the tea plant and they contain water,
      proteins, carbohydrates, minerals, vitamins and polyphenols of the flavonoid
      type. The major flavonoids in green tea are catechins which constitute about one
      third of its total dry weight. The major catechin present is epigallocatechin
      gallate (>50%). New data have increased the interest in green tea or its
      catechins and its role in treatment of cardiovascular disease (CHD) risk factors.
      The aim of the present paper is to review some studies that have found a
      relationship between green tea and CHD risk factors. From some of them it can be
      summarized that of green tea and its catechins consumptions (i) decrease body
      weight by interfering within the sympathoadrenal system and fatty acid synthesis,
      (ii) decrease cholesterol absorption and plasma levels, (iii) have strong free
      radical-scavenging activity inhibiting LDL oxidation, (iv) reduce the adhesion
      molecule expression, (v) have antitrombotic activities by inhibiting platelet
      aggregation and (vi) decrease systolic and diastolic blood pressures. The
      positive effects found suggest that a daily intake of 7 cups of green tea (3.5 g
      catechins) is a good choose for CHD prevention; however, it is still necessary
      more studies to check the action of the green tea and its catechins in humans in
      order to recommended its use in the general population or only in target
      subjects.

PMID- 15969263
TI  - Hospital food handlers in Niteroi, RJ, Brazil: intestinal parasitism.
AB  - A survey for intestinal parasites was carried out with food handlers from two
      private and three public hospitals in Niteroi City, RJ, Brazil. The aim of this
      research was to verify the enteroparasites prevalence in this professional group.
      The investigation was divided in two phases. The first phase consisted of
      interviews with the participants; coproparasitological exams using Lutz, Faust et
      al. and Baermann techniques; under fingernail material analysis, using Mello et
      al. modified method; and educational lectures to food handlers. In the second
      phase, coproparasitological exams were repeated. Positive results were observed
      in 14.2% (17/120) and 17.1% (12/70) of the individuals in the first and second
      phases respectively. The most frequent parasite was Entamoeba coli, detected in
      48.5% (16/33) of the samples with positive results. Under fingernail residues
      were observed in 19.2% (23/120) of the food handlers. E. coli cysts were found in
      one fingernail residue, likewise they were detected in the feces of the same food
      handler. Such data showed a potential transmission risk of intestinal parasites
      by food handling, indicating the need of adopting a diagnosis/orientation
      procedure as a bi-annual routine activity in hospitals, in order to improve the
      food service quality and population health condition.

PMID- 15969264
TI  - Impact of the hypocaloric diet using food substitutes on the body weight and
      biochemical profile.
AB  - Recent studies using balanced hypocaloric diets with food substitutes in some
      meals, have presented positive results. There are no studies with the Brazilian
      population on the efficacy of using food substitute, together with a hypocaloric
      diet. Main objective of this study was to verify the effects of a hypocaloric
      diet using food substitutes as meal replacement on the body weight, lipid
      profile, and glucose and insulin plasma levels. Seventy eight subjects of both
      genders were selected, 20-50 years old, and a body weight index between 25 kg/m2
      and 35 kg/m2. The study lasted for six months and it was divided in 2 phases of
      three months each- mass reduction for 3 months and 3 months for maintenance. The
      sample was randomly divided in two groups: Group A (control- 3 months of general
      nutritional and physical orientation followed by 3 months with 1 meal
      replacement) and Group B (intervention- 2 meals replacement a day plus
      nutritional and physical orientation for 3 months followed by 3 months with 1
      meal replacement). Anthropometric measurements, percent body fat (%BF),
      biochemical profile and intake survey were performed at moments 0, 3 and 6
      months. Both groups showed a significant decrease in %BF, weight, and
      consequently in their BMI, in the third and sixth month of follow up. However,
      weight loss in group B was higher than in group A. At the end of the treatment, 0
      and 25.0% of the patients of the group A and B, respectively, presented a weight
      loss higher than 10% of the initial weight. Comparing the triglycerides, LDL
      cholesterol and glucose levels, between the beginning and after the three and six
      months of treatment, there was a significant reduction in the individuals only in
      group B. In conclusion, the use of food substitutes as meal replacement, together
      with a balanced, hypocaloric diet, proved to be efficient in weight loss for
      Brazilian overweighed individuals.

PMID- 15969265
TI  - [Relationship of deoxypyridinole excretion with bone density, serum estradiol and
      years of postmenopause in Mexican postmenopausic women].
AB  - Deoxypyridinoline is one of the metabolites produced during bone resorption.
      Deoxypyridinoline excretion, unlike other markers, is not affected by diet, or
      the activity level of other tissues. In postmenopausic women, increased excretion
      of deoxypyridinoline has been associated with increased bone mass loss. The
      objective of this study was to determine the association of deoxypyridinoline
      excretion in postmenopausic Mexican women with anthropometric factors, bone mass
      density, calcium and phosphorous intakes, post menopause years and serum levels
      of estradiol. The concentration of deoxypyridinoline in 24 h urine was determined
      utilizing an ELISA technique. An average of 7,27 +/- 5,31 nM Dpd/mM creatinine
      was found. A negative correlation between deoxypyridinoline and serum estradiol
      levels (r = -0.37, p = 0.01) was found. Post menopausic years correlated
      positively (r = .35, p = 0.02) with Dpd. No significant correlation between
      deoxypyridinoline and anthropometric data, bone mass density, calcium and
      phosphorous intakes was found. In conclusion, 30% of the subjects of this study
      had elevated levels of deoxypyridinoline excretion and taking into consideration
      the negative correlation observed with serum estradiol, this segment of the
      population could be at risk for accelerated bone loss. Hormone replacement is
      important for post menopausic women to prevent increased bone loss.

PMID- 15969266
TI  - [Effect of copper supplementation on lipid profile of Venezuelan hyperlipemic
      patients].
AB  - It has been assumed that most Western diets satisfy the requirement of copper/day
      because of ubiquitous presence of this element in most foods. Recent studies have
      shown that dietary copper (Cu) may often fall below the estimated daily
      requirements, what could determine a deficiency of this trace element. This
      deficiency is associated with hypercholesterolemia and hypertrigliceridemia, both
      in human and experimental animals. In the present intervention study was examined
      the effect of the administration of 5 mg of Cu/day in 73 patients (treated
      group), of both genders, with ages between 26 and 48 years, with high serum
      levels of total cholesterol and triglycerides without pharmacological treatment
      and compared with 73 hyperlipemic subjects non-treated with copper (control
      group) who were matched by gender, age, body weight, smoking habits, calories and
      fat intake, and physical activity. Before copper administration, a sample of
      blood was obtained for serum determinations of copper, zinc and lipids. At the
      end of the experimental period (45 days), a new sample of blood was taken for the
      corresponding determinations. The results suggest the existence of a marginal
      deficiency of the trace element in 38% of the subjects and demonstrate that
      copper supplementation decreases (p < 0.05) serum levels of total cholesterol (r
      = -0.976), triglycerides (r = -0.972), LDL-cholesterol (r = -0.961) and zinc (r =
      -0.980) with a slight increment (r = 0.894) of HDL-cholesterol. These findings
      demonstrate that copper can be used in the treatment of the patients with
      hypercholesterolemia and hypertriglyceridemia. The mechanisms by which Cu
      determines these changes are not known.

PMID- 15969267
TI  - [Serum vitamin A during pregnancy and effects on obstetrics and perinatal
      outcomes in HIV infected pregnant women].
AB  - To evaluate serum vitamin levels and its association with obstetrics and
      perinatal results in HIV infected pregnant women. Observational and prospective
      study carried out at Division of Infectious-Contagious Diseases in Gynecology and
      Obstetrics of the University Hospital, Medicine School of Ribeirao Preto,
      University of Sao Paulo, involving 57 pregnant women divided into 3 groups: Group
      1, with 12 normal pregnant women, it was the control group; Group 2, with 20 HIV
      infected pregnant women, using ZDV; and Group 3, with 25 HIV infected pregnant
      women, using therapy I contend ZDV, 3TC and nelfinavir. The evaluation of the
      serum vitamin level was obtained three times during pregnancy at equidistant time
      intervals and in the immediate period after birth. We also evaluated the levels
      of this vitamin and the hemoglobin in the blood of the umbilical cord. We
      obtained maternal and newborn infant anthropometric data, as well as the counting
      of lymphocyte TCD4 and viral load of the HIV during the pregnancy. Reduced serum
      vitamin levels were observed in the Group 1(25%), the Group 2(29,4%) and the
      Group 3(28,6%). Association was not observed between serum levels of maternal
      retinol and the duration of the gestation in groups 2 and 3. In groups 1 and 3,
      an association was observed between the maternal concentration of retinol and the
      newborn hemoglobin (p=0.05). In distinct way to the Control group, association
      was not observed between the retinol levels of the umbilical cord and the weight
      of the newborn in gestations of Group 2, while a trend to this association was
      observed in gestations of Group 3 (p=0.06). We observed high prevalence of
      hipovitaminosis A in the population of this study, regardless of antiretroviral
      scheme used.

PMID- 15969268
TI  - [Prevalence of Cyclospora sp., Cryptosporidium sp, microsporidia and fecal
      coliform determination in fresh fruit and vegetables consumed in Costa Rica].
AB  - The presence of Cyclospora sp., Cryptosporidium sp. and microsporidia and the
      levels of fecal coliforms were determined in lettuce, parsley, cilantro,
      strawberries and blackberries acquired in local agricultural markets of the
      Central Valley of Costa Rica, in order to establish the possible transmission
      risk of these microorganisms and other pathogens from the consumption of these
      raw products. During the second semester of 2001 and the first of 2002, 50
      different samples of each product, 25 taken in the dry season and 25 in the rainy
      season and coming from five different local agricultural markets were evaluated.
      The fecal coliforms count was done according to the technique recommended by
      Vanderzant & Splittstoesser. The parasite determination was done using Zielh
      Nielsen and Weber staining techniques from a sediment obtained through the rinse
      of the mentioned products, using sterile peptonated water 0.1% and centrifuging
      at 900 G for 15 min. One hundred per cent of vegetable samples had fecal
      coliforms and the greatest prevalence was obtained during the rainy season.
      Although all vegetables presented fecal coliforms in high concentrations, lettuce
      and cilantro presented statistical difference between rainy and dry season, being
      greater during the rainy season. Fecal coliforms were not detected in
      strawberries and blackberries probablydue to its low pH. All products evaluated
      presented, at least once, Cryptosporidium sp., Cyclospora sp. and microsporidia,
      showing the risk they represent to Public Health. Cryptosporidium was present in
      all products but strawberries. Microsporidia was present in all products except
      blackberries and Cyclospora was only isolated from lettuce during the dry season.
      These results show the importance of introducing in the country Good Agricultural
      Practices, especially due to the resistance of Cryptosporidium and Cyclospora to
      disinfecting agents.

PMID- 15969269
TI  - [Bacteriological evaluation of fresh tilapia (Oreochromis niloticus) coming from
      the northern region of Costa Rica].
AB  - The following work presents an evaluation of the normal and pathogenic flora
      associated to tilapia (Oreochromis niloticus), since there are no previous
      national studies referred to the microbiological quality of this product. The
      total aerobic plate count, lactic bacteria, Enterococcus sp and Aeromonas sp and
      fecal and total coliform count, and the presence of Listeria sp and Salmonella
      spp from the external surface of tilapias were evaluated. A total of 50 samples,
      coming from San Carlos and Canas zones were transported in ice to the Food and
      Water Microbiology Laboratory, Universidad de Costa Rica, where the laboratory
      analysis were performed, according to the methodology presented by de American
      Public Health Association, 1998. The results obtained confirm the microbiological
      freshness of the product when the analysis was performed, although coliform
      levels were unacceptable. Listeria sp was not found, but the isolation of
      Salmonella spp. confirms the fecal contamination of water where the tilapia is
      grown, aside of the Public Health concern. Also, it was found a high number of
      Aeromonas sp, as part of its normal flora, so we recommend including this genus
      in the quality standards for fresh fish. According to the data obtained, there
      was no significant difference (95% confidence) between the total plate count,
      fecal and total coliforms, Enterococcus sp. and Aeromonas sp. from the samples
      coming from the zones of San Carlos and Canas.

PMID- 15969270
TI  - [Adaptability of sweet corn ears to a frozen process].
AB  - The effects of frozen condition on the quality of three sweet corn ears (2038,
      2010, 2004) and the pattern (Bonanza), were evaluated. Biometrics characteristics
      like ear size, ear diameter, row and kernel deep were measured as well as
      chemical and physical measurement in fresh and frozen states. The corn ears were
      frozen at -95 degrees C by 7 minutes. The yield and stability of the frozen ears
      were evaluated at 45 and 90 days of frozen storage (-18 degrees C). The average
      commercial yield as frozen corn ear for all the hybrids was 54.2%. The industry
      has a similar value range of 48% to 54%. The ear size average was 21.57 cm, row
      number was 15, ear diameter 45.54 mm and the kernel corn deep was 8.57 mm. All
      these measurements were found not different from commercial values found for the
      industry. All corn samples evaluated showed good stability despites the frozen
      processing and storage. Hybrid 2038 ranked higher in quality.

PMID- 15969271
TI  - [Pesticide detection in Costarican vegetables based on the inhibition of serum
      and erythrocytic human cholinesterases].
AB  - A simple and low cost method able to detect the presence of pesticides,
      organophosphates and carbamates based on the inhibition of serum and erythrocytic
      cholinesterases, was used in lettuce (Lactuca sativa), cilantro (Coriandum
      santivum) and celery (Apium graveolens) obtained from the Ferias del Agricultor
      from Valle Central of Costa Rica. The percentage inhibition of cholinesterases is
      related to the presence of plaguicide in the vegetable. Thirteen percent of the
      analyzed samples were positive for plaguicides using serum cholinesterase and 33%
      for erythrocytic cholinesterase. Washing and cooking the vegetables does not
      eliminate the presence of plaguicides but they lower slightly the concentration.
      Statistical evidence (p = 0.0001) indicates that erythrocytic cholinesterase has
      higher analytical sensitivity than serum cholinesterase. It is very important to
      establish the degree of contamination with pesticides in these agricultural
      products because they are exposed to direct contamination by fumigation, soil
      contamination and irrigation water, and are products that are often consumed
      without adequate cooking and washing.

PMID- 15969272
TI  - Physicochemical properties of Venezuelan breadfruit (Artocarpus altilis) starch.
AB  - Artocarpus altilis, seedless variety, is a fruit-producing plant which is
      cultived in Margarita Island, Venezuela, and is consumed by the inhabitants of
      the region. Its chemical composition and physical characteristics were
      determined. The chemical (AOAC and AACC methods), physicochemical, morphometric
      characteristics, viscoamylographic properties and digestibility in vitro of
      starch from Artocarpus were studied. The starch yield was 18.5 g/100 g (dw)w with
      a purity of 98.86%, 27.68 and 72.32% of amylose and amylopectin, respectively.
      Scanning electron microscopy showed irregular-rounded granules. Swelling power,
      water absorption and solubility values were determined and found to be higher
      than that of corn and amaranth starch. The amylographic study showed a
      gelatinization temperature at 73.3 degrees C, with high stability during heating
      and cooling cycles. Artocarpus starch could also be categorized in the group of
      mixed short chain branched/long chain branched glucan starches, this agrees with
      digestibility results that showed a high degree of digestibility in vitro. These
      results might be advantageous in medical and food use.

PMID- 15969273
TI  - Occupational goals of mothers of children with disabilities: influence of
      temporal, social, and emotional contexts.
AB  - OBJECTIVE: The purpose of this study was to describe the occupational concerns
      and goals of mothers who care for children with disabilities. METHOD:
      Retrospective data collected from 38 mothers of children with disabilities using
      the Canadian Occupational Performance Measure (COPM) were analyzed qualitatively.
      RESULTS: Six themes emerged: (I) doing and being alone: taking care of my own
      health and well-being; (II) doing and being with others: expanding my social
      life; (III) improving my child's quality of life; (IV) household management:
      organizing time and resources; (V) balancing work, home, and community
      responsibilities; and (VI) sharing the workload. CONCLUSION: Overarching patterns
      in the data suggested that the occupational performance of mothers of children
      with disabilities is constrained by time, overlaid by difficult emotions, and
      involves a desire for increased social contact. Qualitative analysis of data from
      the COPM may provide insight into contextual factors that affect occupational
      performance as well as signaling point of entry for therapists to facilitate
      client-centered occupational goals.

PMID- 15969274
TI  - Meanings and purposes of caring for a family member: an autoethnography.
AB  - Engagement in two interlinked areas of occupation, familial social participation
      and caring for my father at the end of his life, led to a journey of self
      discovery. A qualitative research methodology, autoethnography, is used to
      develop a narrative that examines engagement in these two occupations before,
      during, and after my father's illness and death. I discuss meanings and purposes
      of familial social participation and caregiving, suggesting that transforming
      fear of death to awareness of death is a central purpose of caregiving.
      Implications for therapists and caregivers include considerations about the value
      of occupation, discussion of a continuum of caregiving, examination of boundaries
      when caring for a parent, thoughts about the roles of altruism, love, anger, and
      "bad faith" in caregiving, and analysis of sons as caregivers for fathers.
      Further research on meanings and purposes of caregiving is proposed.

PMID- 15969275
TI  - Exploring parents' use of strategies to promote social participation of school
      age children with acquired brain injuries.
AB  - OBJECTIVE: To understand parents' perspectives about the strategies they use to
      promote social participation of their school-age children with acquired brain
      injuries (ABI) in home, school, and community life. METHOD: A descriptive
      research design employing a semistructured interview format was used. Interviews
      were conducted in the homes of 16 families of school-age children with ABI
      discharged up to 7 years earlier from one inpatient rehabilitation program. Data
      were examined using content and constant-comparison analyses. RESULTS: Parents
      needed time to allow the recovery process to unfold for themselves and their
      children and developed strategies that fit into or assisted with managing family
      routines. Over time parents developed insight into the activity demands and their
      child's potential success to participate in desired activities. Based on these
      insights, parents used "anticipatory planning," which involved previewing
      upcoming events and activities and using strategies to promote positive and
      prevent negative experiences for their children. Specific strategies that parents
      used to promote social participation were classified into three categories:
      Creating opportunities, teaching skills, and regulating cognitive and behavioral
      function. CONCLUSIONS: Understanding how families use and integrate strategies
      within the context of their daily lives and what factors influence strategy use
      may provide practitioners with insights needed to support families in promoting
      their children's social participation.

PMID- 15969277
TI  - Changes in ADL dependence and aspects of usability following housing adaptation-
      a longitudinal perspective.
AB  - OBJECTIVE: To investigate longitudinal changes in activities of daily living
      (ADL) dependence and aspects of usability in housing among clients receiving
      housing adaptation grants in Sweden. METHODS: The ADL Staircase and the Usability
      in My Home instruments were used to collect data on three occasions: at baseline
      1 month before housing adaptation, at follow-ups 2 to 3 months after housing
      adaptation completion, and after another 6 to 7 months. In all, 131 clients,
      living in ordinary housing 24 to 93 years of age were consecutively enrolled.
      RESULTS: Overall ADL dependence did not change significantly whereas dependence
      in "Bathing" decreased over time. "Activity aspects" and "Personal and social
      aspects" of usability improved at different phases in the process. CONCLUSION:
      This study delivers new insights about the complexity of longitudinal person
      environment-activity transactions, specifically targeting activity and usability.
      The results are useful for developing efficient strategies for evaluating housing
      adaptations within occupational therapy practice and research.

PMID- 15969276
TI  - The ergonomics of caring for children: an exploratory study.
AB  - BACKGROUND: Caring for one's children is among the most ubiquitous of
      occupations. However, few studies have examined the ergonomic risks involved in
      parents caring for children at home. PURPOSE: The purpose of this study was to
      identify the frequency, type, and severity of musculoskeletal symptoms in parents
      of children less than 4 years old. The study further examined the factors that
      contribute to musculoskeletal pain in this sample. METHODS: A convenience sample
      of 130 parents with children younger than 4 years old completed a seven-page
      survey that included questions related to the parents' demographics, their
      musculoskeletal discomfort, their performance of child-care tasks with high
      biomechanical risks (such as carrying a child in a car seat), and parents'
      perceived psychological strain related to caring for their children. RESULTS:
      Ninety-two percent (92%) of the providers were mothers. Sixty-six percent (66%)
      of the sample reported the presence of musculoskeletal pain. The parts of the
      body most affected were the low back (48%), neck (17%), upper back (16%), and
      shoulders (11.5%). Factors associated with musculoskeletal pain were performing
      child-care tasks defined as having high biomechanical risks (p = .001), the
      perception that caring for children is highly demanding (p = .003), and
      performing hobbies less than 1 hour per week (p = .04). Parents' working status,
      age, and participation in other daily activities were not significantly related
      to musculoskeletal discomfort. CONCLUSION: This study demonstrates the high
      prevalence of musculoskeletal pain in parents of children under the age of 4
      years. It underscores the association between physical and psychological factors
      in the development of musculoskeletal discomfort. It suggests the need for
      occupational therapy wellness programs that focus on preventing musculoskeletal
      discomfort and providing support for the parenting role.

PMID- 15969278
TI  - Acquisition and integration of low vision assistive devices: understanding the
      decision-making process of older adults with low vision.
AB  - The purpose of this study was to describe how older adults with low vision make
      decisions to use low vision assistive devices (LVADs). Analysis of participants'
      narratives, from both group and individual interviews, revealed three topic areas
      affecting device use. Two are discussed in this paper: Experiences and
      Characteristics Leading to Successful LVAD Use Decision Making and Challenges to
      Successful LVAD Use Decision Making. The third, Adjustment to Low Vision
      Disability, is briefly discussed. Of particular importance to occupational
      therapy practitioners in the growing field of low vision rehabilitation was the
      value placed on low vision rehabilitation services to assist with acquiring
      devices and integrating them into daily routines. Occupational therapy services
      were highly regarded. Participants demonstrated the importance of becoming a part
      of a supportive network of people with low vision to gain access to information
      about resources. They emphasized the need for systems and policy changes to
      reduce barriers to making informed decisions about LVAD use. Results indicate
      that occupational therapists working in low vision can support clients by
      facilitating development of a support network, acting as liaisons between clients
      and other health practitioners, especially ophthalmologists, and encouraging
      policy development that supports barrier-free LVAD acquisition and use. These
      topics should be incorporated into continuing and entry-level education to
      prepare practitioners for leadership in the field of low vision rehabilitation.

PMID- 15969279
TI  - A comparative analysis of case presentation modalities used in clinical reasoning
      coursework in occupational therapy.
AB  - This study used mixed methods to compare four different styles of case
      presentation in a course designed to develop the clinical reasoning skills of
      master's level occupational therapy students. Modalities used to present cases
      were printed text, videotape, live interview, and CD-ROM movies delivered on an
      Internet platform. The researchers sought to determine the relative merits and
      limitations of each modality from both pedagogical and practical standpoints.
      Results indicate that the choice of modality does not compromise the ability of
      students to meet learning objectives related to clinical reasoning; however,
      several advantages and disadvantages with respect to practical aspects of
      presentation and learning were identified from instructor and student
      perspectives. The strength of the overall instructional format, and decisions
      concerning the amount and type of information provided in the cases were found to
      be more relevant to the quality of the learning experience than the modality of
      presentation. Recommendations are provided for structuring clinical reasoning
      learning experiences that combine the best features from the case modalities
      examined in this study.

PMID- 15969280
TI  - Cultural competency in occupational therapy: beyond a cross-cultural view of
      practice.
AB  - The purposes of this paper are two. The first purpose is to contribute to
      cultural competence in occupational therapy practice. The second is to contribute
      to occupational therapy literature about culture and cultural analysis related to
      practice. This paper introduces a cultural analysis of stories about the
      therapeutic process with two Japanese therapists and their Japanese patients. Two
      therapeutic situations, including therapists' and their patients' experiences,
      are interpreted by the author, a Japanese occupational therapist, as critical
      incidents for reflection to improve culture general competence. The stories
      illustrate the patients' perception of life with illness and, particularly, the
      emergence of their cultural values within the therapy process. The analyses focus
      on how an understanding of the patients' illness experience is integrated into
      the therapy process and how the therapeutic interventions reflect the culture. In
      one case, the therapeutic occupation of cooking links to the meaning found in the
      traditional Japanese woman's role. In the second case, the therapist-patient
      relationship, based on local rather than western social relationships, promoted
      the patient's engagement in meaningful occupations. Reflection on these stories,
      which illustrate an alternative cultural view of occupations and therapeutic
      relationships, may assist occupational therapists in the development of improved
      level of cultural competence.

PMID- 15969281
TI  - Sensory modulation and affective disorders in children and adolescents with
      Asperger's disorder.
AB  - OBJECTIVE: The purpose of the study was to determine if there were significant
      relationships between dysfunction in sensory modulation, symptoms of affective
      disorders, and adaptive behaviors in children and adolescents with Asperger's
      disorder between 6 and 17 years of age. METHOD: Parents of 50 children and
      adolescents between 6 and 17 years of age diagnosed with Asperger's disorder
      based on the Diagnostic and Statistical Manual of Mental Disorders-IV criteria
      completed the (a) Sensory Profile for children 6 to 10 years of age or the
      Adolescent/Adult Sensory Profile for adolescents 11 to 17 years of age; (b) the
      Adaptive Behavior Assessment System: Parent Version; (c) Revised Children's
      Manifest Anxiety Scale Adapted Parent's Version; and (d) the Children's
      Depression Inventory Adapted Parent's Version. Descriptive statistics and the
      Pearson product-moment coefficient of correlation calculations were used for data
      analysis. RESULTS: The results indicated that there were significantly strong
      positive correlations between sensory defensiveness and anxiety (r = .476, p =
      .000) in children and adolescents with Asperger's disorder. There were also
      significant relationships between symptoms of depression and hyposensitivity in
      the total group (r = .214, p = .05) and the older group (r = .492, p = .027).
      There were no significant relationships between depression and overall adaptive
      behavior (r = -.243, p = .089) or anxiety and overall adaptive behavior (r = 
      .108, p = .455). Significantly strong inverse relationships were found between
      the specific adaptive behaviors of functional academics, leisure, social skills,
      and symptoms of depression. Functional academics were also significantly
      inversely related to anxiety. Specifically, sensory hyper- and hypersensitivity
      were significantly inversely related to community use and social skills.
      CONCLUSION: The data supports positive relationships between anxiety and sensory
      defensiveness in all age ranges and a relationship between depression and
      hyposensitivity in older children. Stronger inverse relationships were apparent
      between specific adaptive behaviors including: (a) symptoms of depression and
      functional academics, leisure, social skills; (b) anxiety and functional
      academics; and (c) both sensory hyper- and hyposensitivity and community use and
      social skills. In this study, as the symptoms of affective disorders increased in
      children and adolescents with Asperger's disorder, the functional performance in
      the adaptive behaviors of functional academics and social skills appeared to
      decrease. Performance in the adaptive behaviors of community use and socials
      skills appeared to decrease as symptoms of dysfunction in sensory modulation
      increase. Further research is necessary to determine the impact of treatment for
      dysfunction on sensory modulation on affective disorders and performance in
      specific adaptive behaviors.

PMID- 15969282
TI  - Positive consequences of surviving a stroke.
AB  - This exploratory study focused on gaining insight into the psychological
      experience of stroke survivors undergoing inpatient rehabilitation. Specifically
      it investigated whether stroke survivors undergoing inpatient rehabilitation were
      able to identify any positive consequence of their stroke. This phenomenon, also
      know as benefit finding or positive reframing, has recently received more
      attention in the coping literature examining reactions to severe illness. Using a
      case series methodology and qualitative analytic techniques, 16 stroke survivors
      were interviewed using standardized open-ended questions related to
      identification of positive consequences attributed to surviving a stroke. Sixty
      three percent of the patients interviewed were able to identify positive
      consequences of their stroke. The following five themes regarding positive
      consequences of stroke emerged from this case series: increased social
      relationships, increased health awareness, change in religious life, personal
      growth, and altruism. It was concluded that some individuals who have survived an
      acute stroke are able to reframe their experience in a positive light. This study
      provides occupational therapists and others with further insight into the coping
      mechanisms of those individuals who have survived a stroke. The need for further
      research is stressed.

PMID- 15969283
TI  - A conceptual framework to increase usability of outcome research for evidence
      based practice.
AB  - Although evidence-based practice is the current practice approach recommended for
      use in occupational therapy, practitioners often report difficulties in using
      research evidence because of its content and presentation. This paper discusses a
      conceptual model that researchers can use to create research evidence that is
      easier for practitioners to understand and use. The Diffusion of Innovations
      Theory is used as a framework to identify desirable characteristics that may
      facilitate practitioners' adoption and utilization of research evidence. The
      concepts of social validity, ecological validity, and clinical significance are
      presented and discussed as ways to create those desirable characteristics that
      could make research information more usable for evidence-based practice. Examples
      for implementation of the conceptual model are also discussed.

PMID- 15969284
TI  - International conference on evidence-based practice: A collaborative effort of
      the American Occupational Therapy Association, the American Occupational Therapy
      Foundation, and the Agency for Healthcare Research and Quality.

PMID- 15969285
TI  - Generating electricity from wastewater treatment.

PMID- 15969286
TI  - Selective extraction of trace mercury and cadmium from drinking water sources.
AB  - In this paper, a new alternative method, i.e., selective extraction by weakly
      basic anion exchange resin, has been developed for the removal of trace cadmium
      and mercury ions from drinking water sources. The mechanism of heavy metal
      removal is based on selective extraction as the results of LEWIS-base-acid
      interactions. Transfer of trace mercury species from liquid to resin phase
      coincides well with the performance of film diffusion. The results demonstrated
      that the presence of chlorine has a negligible influence on the removal of
      mercury. However, humic acids can strongly bind mercury by the formation of
      complex compounds and therefore become the obstacle in the diffusion progress. At
      neutral or base pH, the resin material exhibits the favorable uptake of heavy
      metals. In filter experiments, the studied resin material offers favorable
      properties in the selective extraction of trace mercury and cadmium.

PMID- 15969287
TI  - Utility of stormwater monitoring.
AB  - Stormwater runoff is now a major contributor to the pollution of coastal waters
      in the United States. Public agencies are responding by requiring stormwater
      monitoring to satisfy the National Pollutant Discharge Elimination System
      stormwater permit. However, studies to understand the utility of the current
      programs or to improve their usefulness have not yet been performed. In this
      paper, we evaluate the land-use-based program, the industrial stormwater permit
      program, and beach water-quality monitoring in the County of Los Angeles,
      California, to determine if the results will be helpful to planners and
      regulators in abating stormwater pollution. The utility of the program has been
      assessed based on the programs' ability to accurately estimate the emissions for
      different classes of land use. The land-use program appears successful, while the
      industrial monitoring program does not. Beach water-quality monitoring suffers
      from a lack of real-time monitoring techniques. We also provide suggested
      improvements, such as sampling method and time, and parameter selection.

PMID- 15969288
TI  - Optimization of the intermittent aeration in a full-scale wastewater treatment
      plant biological reactor for nitrogen removal.
AB  - The optimization of the intermittent aeration in a full-scale biological reactor
      treating municipal and industrial wastewater has been studied by means of an
      experimental design, where the main factors considered have been the on-off
      period of aeration and the dissolved-oxygen set point. The objective of the work
      has been to determine the optimal configuration of the aeration control to
      achieve a simultaneous removal of carbon (expressed as chemical oxygen demand
      [COD]) and nitrogen. The results were obtained in a full-scale bioreactor located
      at the wastewater treatment plant of Sant Celoni (Barcelona, Spain), where a
      nitrogen removal based on a nitrification-denitrification process is being
      tested. It has been shown that the crucial parameter to ensure a complete removal
      of COD and nitrogen is to give the system a long time of on-off aeration to
      complete both the nitrification and the denitrification processes, whereas the
      dissolved-oxygen set point has a minor influence on the overall performance. The
      results presented can be applied to a great number of similar systems, in which a
      nitrogen removal, based on a nitrification-denitrification scheme, is currently
      being tested or implemented.

PMID- 15969289
TI  - Application of anaerobic and aerobic activated sludge to phosphorus-deficient
      wastewater treatment.
AB  - Anaerobic and aerobic (AnA) and completely aerobic (CA) sequencing-batch reactors
      (SBRs) were used to investigate the suitability of the AnA process for treating
      phosphorus (P)-deficient wastewaters with highly variable influent chemical
      oxygen demand (COD) loading. Both SBRs were subjected to influent COD loading
      patterns (LPs) that simulated (1) daily COD loading fluctuations, (2) weekend
      shutdowns, and (3) long weekend or holiday shutdowns. During LP 1, the AnA SBR
      produced lower average effluent soluble phosphorus concentrations than CA SBR
      (0.4 vs. 1.0 mgP/L). A similar result was observed during LP 2, but effluent
      acetate was detected after the first high COD loading cycle of the weekday
      loading period. During LP 3, the volatile suspended solids content of both
      reactors dropped sharply, and the effluent quality of both SBRs deteriorated.
      Model predictions suggest that the AnA process is stable when treating LP 1, but
      eventually fails when treating LP 2.

PMID- 15969290
TI  - Nitrogen transformations modeling in subsurface-flow constructed wetlands.
AB  - Subsurface-flow constructed wetlands (CWs) wastewater treatment typically results
      in satisfactory organics removal. However, the removal of nutrients, particularly
      nitrogen, is often unreliable, and typically less than desired, and nitrogen
      transformations in wetlands systems are not well-understood. The principal
      objective of this study was to establish a basis for quantification of nitrogen
      transformations through subsurface flow CW systems. Actual performance data from
      a full-scale facility located near Lincoln, Nebraska, were used to calibrate a
      proposed nitrogen transformations model, which, in turn, was used to replicate
      and predict the wetlands performance. To realize this objective, a compartmental
      analysis technique, which uses a set of differential equations and nonlinear
      optimization numerical methods, was used for solving nitrogen transformation
      rates and for predicting wetland performance. The model satisfactorily reproduced
      the mean effluent concentrations for organic nitrogen, ammonium-nitrogen, and
      nitrate-nitrogen, but with lesser accuracy with respect to peak high and low
      effluent concentrations. Nitrogen mass balance in the wetland was used to
      identify likely nitrogen transformation pathways. Generally, it was found that
      approximately one-third of the influent nitrogen mass was removed through
      nitrification and denitrification, one-third was removed through vegetative
      assimilation, and the remainder was discharged in the wetland effluent.

PMID- 15969291
TI  - Ultrasonic destruction of surfactants: application to industrial wastewaters.
AB  - This research focused on the use of sonication to destroy surfactants and surface
      tension properties in industrial wastewaters that affect traditional water
      treatment processes. We have investigated the sonochemical destruction of
      surfactants and a chelating agent to understand the release of metals from
      surfactants during sonication. In addition, the effects of physical properties of
      surfactants and the effect of ultrasonic frequency were investigated to gain an
      understanding of the factors affecting degradation. Sonochemical degradation of
      surfactants was observed to be more effective than nonsurfactant compounds. In
      addition, as the concentration is increased, the degradation rate constant does
      not decrease as significantly as with nonsurfactant compounds in the near-field
      acoustical processor reactor. The degradation of metal complexes is not as
      effective as in the absence of the metal. However, this is likely an artifact of
      the model complexing agent used. Surfactant metal complexes are expected to be
      faster, as they will accumulate at the hot bubble interface, significantly
      increasing ligand exchange kinetics and thus degradation of the complex.

PMID- 15969292
TI  - Fifteen years of offgas transfer efficiency measurements on fine-pore aerators:
      key role of sludge age and normalized air flux.
AB  - Fine-pore diffusers, often called fine-bubble diffusers, have nearly replaced
      coarse bubble diffusers in municipal wastewater treatment over the past 20 years.
      The rapid increases in energy costs, which began in the 1970s, created financial
      incentives to upgrade to this more expensive and maintenance-intensive method of
      aeration. Fine-pore diffusers have the added benefit of reducing volatile organic
      compound stripping and reduced aeration heat loss. This paper summarizes 15 years
      of oxygen transfer efficiency measurements using the offgas technique.
      Efficiencies are shown for different types of diffusers at various tank
      geometries (depth, diffuser size, and number), airflow rates, and mean cell
      retention times (MCRT or sludge age). By normalizing the airflow rates per unit
      of depth and diffusing area, efficiencies measured in different plants can be
      compared. The results show that aeration efficiencies are logarithmically related
      to the ratio between MCRT and the normalized air flux, with transfer rates
      suppressed by low MCRT or high normalized air flux systems. There is no evidence
      for different alpha factors among the different types of fine-bubble diffuser
      types.

PMID- 15969293
TI  - Formation and biodegradation of toluene in the anaerobic sludge digestion
      process.
AB  - The formation of toluene in municipal anaerobic primary and secondary sludge
      digestion processes was investigated. Experiments were carried out in a large
      laboratory-scale reactor using sludge from a primary settling tank of a municipal
      treatment plant. It was found that toluene was produced in the supernatant in
      relatively large concentrations for almost all cases tested. The concentration of
      toluene varied and was found to depend on the stage of the anaerobic process.
      During the acidity phase, which is the first stage of anaerobic digestion, an
      increase of toluene concentration was observed, while in the transition period,
      from the acidity phase to methanogenesis, the toluene concentration decreased. It
      was concluded that biosynthesis of toluene occurs in the acidogenic phase, while
      biodegradation was prevalent in the methanogenic stage. Depending on the type of
      experiments, an increase of toluene from a base value of approximately 200
      microg/L up to 20,000 and 42,000 microg/L was measured in the first stage of
      anaerobic digestion. In the subsequent methane-production stage of digestion, the
      estimated rate of toluene decrease (biodegradation) varied from 400 to 900
      microg/L-d.

PMID- 15969294
TI  - Uncertainty analysis in QUAL2E model of Zayandeh-Rood River.
AB  - Water-quality modeling and prediction is a complicated task because of inherent
      randomness and uncertainties associated with various processes and variables
      throughout the stream environment and the lack of appropriate data. Hence, the
      results of mathematical models are always approximate, lying within an
      uncertainty. This paper describes and demonstrates the application of the U.S.
      Environmental Protection Agency's water-quality model, QUAL2E-UNCAS, to the
      Zayandeh-Rood River in Iran. First-order reliability analysis is used to examine
      the variability of predicted water-quality parameters of total dissolved solids,
      dissolved oxygen, and biochemical oxygen demand. This analysis also determines
      key sources of uncertainty affecting prediction of the water-quality parameters.
      The results show that reliability analysis can help water-quality modelers and
      planners to quantify the reliability of the water-quality predictions and to
      carry out more efficiently planned sampling and data collection programs to
      reduce model-prediction uncertainty.

PMID- 15969295
TI  - Integrating decay, storage, kinetic selection, and filamentous backbone factors
      in a bacterial competition model.
AB  - Filamentous bulking in activated sludge systems occurs when filamentous organisms
      outgrow floc-forming bacteria and interfere with sludge settling. The competition
      between filaments and floc formers has been described previously using the
      kinetic selection and filamentous backbone theories. We hypothesized that
      differences in decay rates and storage abilities also affect this competition. We
      tested this hypothesis by integrating these four factors into a substrate
      utilization model to predict and explain coexistence in a completely mixed
      reactor. In addition, filamentous and nonfilamentous sludges were developed in
      laboratory-scale reactors and analyzed to determine decay rates. The modeling
      results showed coexistence of the two organism types, and sensitivity analysis
      showed that the kinetic parameters, storage rate constants, and backbone
      coefficient had the greatest effect on the simulation results. Monte Carlo
      simulation showed the effect of storage, and the ranges of dilution rates wherein
      one group outcompeted the other were delineated.

PMID- 15969296
TI  - Anaerobic biodegradation of methyl tert-butyl ether under iron-reducing
      conditions in batch and continuous-flow cultures.
AB  - The feasibility of biodegradation of the fuel oxygenate methyl tert-butyl ether
      (MTBE) under iron-reducing conditions was explored in batch and continuous-flow
      systems. A porous pot completely-mixed reactor was seeded with diverse cultures
      and operated under iron-reducing conditions. For batch studies, culture from the
      reactor was transferred anaerobically to serum bottles containing either MTBE
      alone or MTBE with ethanol (EtOH) and excess electron acceptor. In the continuous
      flow reactor, MTBE conversion to tert-butyl alcohol (TBA) was observed after 181
      days of operation, and stable removal was achieved throughout the remainder of
      the study. Simultaneously, both the MTBE only and the MTBE and EtOH iron-reducing
      batch serum bottles also began to degrade MTBE. Bottles were respiked and the
      degradation rate was determined to be 2.36 +/- 0.10 x 10(-4) mmol MTBE/min-kgVSS.
      The EtOH present with MTBE degraded faster (7.76 +/- 0.08 x 10(-3) mmol EtOH/min
      kg VSS) but did not have a noticeable effect on the rate of MTBE degradation. No
      evidence of TBA degradation was observed by the iron-reducing cultures.
      Stoichiometry of iron utilization was determined from the iron balance of the
      continuous-flow reactor, and it was found that the bulk of the electron acceptor
      was required for energy and maintenance with little remaining for cell synthesis.
      This is consistent with a yield coefficient of less than 0.1. Molecular analysis
      of the iron-reducing culture by denaturing gradient gel electrophoresis indicated
      that uncultured strains of delta-Proteobacteria were dominant in the reactor.

PMID- 15969297
TI  - The Joint Commission's Sentinel Event Policy: ten years of improving the quality
      and safety of health care.

PMID- 15969298
TI  - Laboratory cytology proficiency testing update.

PMID- 15969299
TI  - New accreditation product approved for systems under the ambulatory and home care
      programs.

PMID- 15969300
TI  - Medical liability system hinders improvements in patient safety: Joint Commission
      expert panel offers solutions to crisis.

PMID- 15969301
TI  - Revisions to participation requirements for the Cooperative Accreditation
      Initiative.

PMID- 15969302
TI  - The design of multicentre trials.
AB  - The analysis of data collected in multicentre trials offers challenges because
      the data from the individual centres must be combined in some way to give an
      overall evaluation of the differences between the treatments in the trial. We
      propose that the combined response to treatment (CRT) be used as this overall
      measure. The definition and estimation of the CRT can be derived from either a
      fixed-effects or a random-effects model. For the latter we introduce the ECRT-
      the expected combined response to treatment. We describe and compare both types
      of model and express our preference for the random-effects model. We stress that
      the number of patients enrolled at a centre is a random variable and show that
      this source of randomness inflates the variance of the estimated ECRT.
      Variability in enrolment rates over the centres further inflates this variance. A
      simple conclusion from our results is that if variability in the treatment and
      centre effects, in the enrolment time, in the number of patients enrolled at a
      centre and in the enrolment rates is not properly accounted for, then an
      underpowered trial may result. Using properties of estimators generated by the
      random-effects model we propose methods for determining the optimal number of
      centres and total number of patients to enrol in a trial to minimize a loss
      function that accounts for centre and patient costs and loss of revenue. We
      discuss variants of the loss function and corresponding optimization problems for
      different types of enrolment. We end the paper with brief generalizations of the
      developed techniques to the case where the response is binary.

PMID- 15969303
TI  - Bayesian analysis of multicentre trial outcomes.
AB  - Bayesian methods provide flexibility in the analysis of data from multicentre
      trials that would be difficult to achieve by other means. This paper illustrates
      some useful applications of Bayesian methods to the analysis of multicentre
      trials, with emphasis on insights that would be difficult to obtain using
      conventional frequentist methods. Two trials provide data for illustration: a
      large multicentre trial comparing two doses of a drug with placebo with respect
      to an essentially continuous measurement for which the original analysis revealed
      a significant treatment by centre effect, and a large multicentre trial with
      intraclass correlation induced by a categorical outcome of up to four episodes of
      heartburn reported by individual patients. The data from both trials had been
      analysed previously using conventional frequentist methods. Both sets of data
      were reanalysed using Bayesian and empirical Bayesian methods; all of the
      analyses provided the same conclusions for the key questions regarding treatment
      differences. The Bayesian methods provided some insights useful for model
      checking and also provided a way to explore some important quantitative aspects
      about the magnitude of treatment effects.

PMID- 15969304
TI  - Randomization-based nonparametric methods for the analysis of multicentre trials.
AB  - Multicentre trials offer several advantages over single centre trials in clinical
      research, including the ability to recruit patients at a faster rate over the
      course of the study, increased generalizability through the use of a broader
      patient population, and the ability to shed light on the replication of findings
      at multiple centres in a single study. A nonparametric approach to the analysis
      of multicentre trial data provides a convenient way for addressing the role of
      centres as well as baseline covariables during data analysis. With the use of
      randomization-based nonparametric methods, the strategy for evaluating the null
      hypothesis of no treatment effect can be prespecified during study planning
      without requiring a specific structure for the relationship of response criteria
      (or endpoints) to centres, covariables, or potential interaction terms. Further,
      the basis of inference for the application of these methods is the randomization
      mechanism, and the population to which inference can be directly made is the
      study population itself. No assumptions about underlying distributions, data
      structures, likelihood functions, or samples from super populations of inference
      are required. A three-step approach is proposed for handling centres via
      randomization-based nonparametric methods. In Step 1, a test of overall treatment
      effect is carried out using data from all centres simultaneously, without any
      assumption about treatment by centre interaction. In Step 2, the question of
      treatment by centre interaction is addressed, usually through the use of
      parametric multiple regression methods. In cases with suggestion of such
      interaction, Step 3 is conducted to evaluate different weighting schemes in
      forming pairwise treatment comparisons averaged across centres to assess the
      robustness of treatment effects observed in Step 1. An attractive inferential
      feature of this three-step approach is that the Type I error for the test of
      treatment effect is controlled by requiring statistical significance at each step
      to proceed to the next step. Extended Mantel-Haenszel methods with stratification
      adjustment for centre can be used to provide a nonparametric assessment of
      treatment effect. When adjustment for other covariates, such as baseline values,
      is desired, the more recent nonparametric analysis of covariance methods are
      available. Both methods are easy to use, require no assumptions beyond that of a
      valid randomization mechanism, and can be applied in a similar manner to
      dichotomous, ordinal, failure time, or continuous response criteria (endpoints).
      The methods are illustrated using data from a confirmatory clinical trial of a
      therapeutic agent for the treatment of dry eye disease.

PMID- 15969305
TI  - Multicentre trials: a US regulatory perspective.
AB  - Multicentre trials are very common in the field of drug development. In recent
      years, multicentre trials have taken on a multinational and multiregional aspect.
      We provide a conceptual framework for the use of multicentre trials in the
      context of drug development, from the perspective of drug regulation in the
      United States. In this paper, we review some regulatory history, milestones and
      standards as they relate to multicentre trials. Special attention is given to the
      similarities and differences in the approaches to multicentre trials in the
      following documents; Guideline for the Format and Content of the Clinical and
      Statistical Sections of New Drug Applications, International Conference on
      Harmonization, Draft Guideline on Statistical Principles for clinical trials and
      the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human
      Drug and Biologic Products. The paper includes a consideration of some of the
      issues in the analysis of data from multicentre trials.

PMID- 15969306
TI  - [The role of drug metabolizing enzymes in the effect and side-effect of the
      drugs].
AB  - The authors give an overview on the role of drug metabolizing enzymes in the
      effect and side-effect of drugs. They describe the properties of cytochrome P450
      and other phase I enzymes (hydrolases, flavin-monooxygenases), as well as of
      phase II. enzymes (glucuronyl-, sulfate-, glutathione-, acetyl-,
      methyltranferases), their polymorphism, inductive and inhibition properties. The
      possible drug-drug interactions are discussed in detail.

PMID- 15969307
TI  - [Bronchiolitis obliterans syndrome in lung transplant recipients].
AB  - Bronchiolitis obliterans syndrome in lung transplant recipients. The leading
      cause of late graft loss after lung transplantation is bronchiolitis obliterans
      syndrome. The process is a manifestation of chronic rejection, and is
      characterized by an excessive fibroproliferation in the small airways, leading
      progressively to luminal obliteration and graft injury. Both alloantigen
      dependent (acute rejection, histocompatibility) and alloantigen-independent
      (ischaemia-reperfusion injury, cytomegalovirus infection, gastroesophageal reflux
      disease) risk factors may contribute to the development of the disease. Early in
      the process, damage to the airway epithelium occurs, which then triggers a
      massive influx of alloreactive T-cells into the graft tissue. Activated T-cells
      release a wide range of cytokines and growth factors, which in turn are capable
      of stimulating cellular proliferation and matrix protein synthesis in fibroblasts
      as well as in airway smooth muscle cells. Clinically, a decline in lung functions
      together with nonspecific symptoms can usually be observed in these patients,
      while later in the disease course recurrent respiratory tract infections are more
      common. Up till now, no effective therapy is available for bronchiolitis
      obliterans syndrome, however, certain immunosuppressive regimens may slow down
      the progression of the disease.

PMID- 15969308
TI  - [Dilemmas arising from surgical treatment of epiphrenic diverticulum].
AB  - INTRODUCTION: Epiphrenic diverticulum cannot be considered a primary anatomical
      alteration, there is a manometrically verifiable motility disturbance in the
      background. OBJECTIVES: To determine the place, type and time of surgical
      solution in the treatment. PATIENTS: Between 1999 and 2004 seven patients were
      treated for epiphrenic diverticulum causing complaints. Average age was 61 years,
      and the leading symptom was dysphagia and regurgitation. Motility abnormalities
      characteristic of achalasia in four cases, hypertensive LES in three cases, and
      incompetent and normal LES, and diffuse esophageal spasm in one patient each
      could be revealed. The size of diverticuli varied between 5-9 cm. RESULTS: In
      four cases transthoracic diverticulectomy myotomy and partial antireflux plasty,
      in two cases esophagus resection, and in the case of one patient myotomy and
      fundoplication was performed. In the removed diverticuli an ulcer and a malignant
      transformation in one case each was detected. No major complications could be
      observed. Six patients are completely satisfied with the operation, only one
      reported well tolerable occasional regurgitations. CONCLUSION: Even in the era of
      minimal invasive surgery the traditionally performed, combined -
      diverticulectomy, myotomy, fundoplication - operative solution should be
      considered the gold standard. Surgical intervention is justified even for
      accidentally discovered symptomless patients, due to the considerable potential
      complications of the disease.

PMID- 15969309
TI  - [Intranasal phototherapy for the treatment of allergic rhinitis].
AB  - INTRODUCTION: Allergic rhinitis is a frequent disease, accompanied by significant
      social-economic costs and a negative impact on the quality of life. Phototherapy
      has a profound immunosuppressive effect and is effectively used in the treatment
      of several immune mediated skin diseases such as atopic dermatitis. AIMS: The
      authors investigated the efficacy of intranasal phototherapy with a combination
      of low doses of ultraviolet-B, ultraviolet-A and visible light in allergic
      rhinitis. METHODS: A randomized, double-blind, placebo-controlled study was
      conducted in patients with a history of at least 2 years of moderate to severe
      ragweed-induced allergic rhinitis that was not controlled by anti-allergic drugs.
      Intranasal phototherapy was performed 3 times a week for 3 weeks. As placebo low
      intensity visible light was used. RESULTS: Phototherapy resulted in a significant
      improvement of clinical symptoms for nasal itching, rhinorrhea, sneezing and
      total nasal score. Scores for nasal obstruction slightly improved during
      phototherapy while a significant increased was found in the placebo group. In the
      overall efficacy assessment, both patients and investigators found phototherapy
      significantly more efficient than placebo. Phototherapy was well tolerated, the
      only side effect was the slight dryness of the nasal mucosa. CONCLUSIONS: These
      results suggest that intranasal phototherapy is effective for the treatment of
      allergic rhinitis, and opens up new opportunities for the treatment of immune
      mediated mucosal diseases.

PMID- 15969310
TI  - [Acute ST segment elevation during noncardiogenic shock].
AB  - Transient elevation of the ST segment was observed in a patient during
      noncardiogenic shock. The coronarography was negative. The patient received
      dopamine infusion. The 48 yr-old man had Crohn disease with septicaemia and ARDS.
      The exact pathomechanism is not known, but the negative coronarography ruled out
      the epicardial coronary disease. The suggested mechanisms are dopamine induced
      coronary vasoconstriction or complement activation.

PMID- 15969311
TI  - [Management of chronic heart failure].

PMID- 15969313
TI  - [Clinical trials in very elderly people: the point of view of geriatricians].
AB  - BACKGROUND: Very elderly subjects (aged > or =80 years) and polypathological
      elderly subjects experience frequent and serious adverse drug effects. They are
      nevertheless still excluded from clinical research. METHODS: We questioned
      geriatricians through a questionnaire about the usefulness and feasibility of
      randomised controlled trials (RCTs) in this population. RESULTS: Forty-eight
      percent of geriatricians questioned did participate in RCTs, but 96.8% considered
      that RCTs including very elderly subjects were scientifically necessary. Among
      geriatricians who never participated in RCTs, 36% were never contacted regarding
      participation in such clinical research. The most important difficulties in
      developing RCTs in very elderly subjects were methodological difficulties (narrow
      eligibility criteria incompatible with patient heterogeneity) and those
      associated with patient consent. For 38.2% of the geriatricians, the fact that
      pharmaceutical companies are under no obligation to promote RCTs in very elderly
      subjects represents a major obstacle in the development of such RCTs.
      CONCLUSIONS: The development of RCTs involving very elderly subjects depends
      first on a political choice, together with an adapted regulatory framework.

PMID- 15969312
TI  - [Pharmacology of Alzheimer's disease: where do we go from here?].
AB  - Ten years after the introduction of the first drug for the treatment of
      Alzheimer's disease, tacrine, it seems appropriate to reappraise the
      pharmacological processes of innovation in the field of research in dementia. The
      aim of this review is to pinpoint concrete improvements achieved in this field,
      in terms of experimental methods and clinical evaluation of the compounds, as
      well as the neurochemistry of the disease and cellular targets deserving of
      initial consideration. * The article first considers the use of animal models of
      Alzheimer's disease, which are classified according to two categories: animals
      with lesions of some neuronal pathways specifically implicated in clinical
      symptoms (i.e. lesions of the nucleus basalis of Meynert, the origin of
      cholinergic projections to the cortex underlying memory processes); and
      transgenic models, which are intended to reproduce some of the neuropathological
      hallmarks of Alzheimer's disease. Drugs can be tested in animals with such
      alterations for their effect on neuropathology, neurochemistry and behavioural
      disturbances. More recently, in silico models have been developed, which offer
      the possibility of simulating the pharmacodynamic effects of drugs in specific
      areas of the brain. These experiments are helpful in distinguishing purely
      symptomatic effects from disease-modifying effects, the latter being the ultimate
      goal of the modern pharmacology of dementia. * The second breakthrough considered
      in this article is the codification and standardisation of clinical methods for
      obtaining a more accurate and earlier diagnosis (the recent introduction of the
      concept of "Mild Cognitive Impairment", which includes patients who will later
      develop a true clinical dementia syndrome). In that respect, the determination of
      the biological markers of Alzheimer's disease (apolipoprotein E, amyloid
      substance, protein-tau, isoprostane) as well as progress in neuroimaging
      (functional positron emission tomography [fPET]-scan, single photon emission
      computed tomography [SPECT], functional nuclear magnetic resonance [fNMR]) are
      discussed in terms of their potential as new tools in the early stages of drug
      development (surrogate markers). The methods used during the comparative clinical
      trials (phase III) have been elaborated and internationally standardised during
      the assessment of the different acetylcholinesterase inhibitors (AChE-I), with
      the knowledge that, since 1994, four of these have been officially approved:
      tacrine, donepezil, rivastigmine and galantamine; the same methods have been used
      for developing memantine, a recently-launched modulator of glutamatergic
      neurotransmission. The validated scales now take into consideration not only the
      cognitive dimensions of Alzheimer's disease but also the behavioural symptoms,
      with the introduction of the concept of BPSD (behavioural psychological symptoms
      of dementia). Some proposals to improve this clinical assessment of anti-dementia
      drugs are presented here. * The section of this article dealing with prospective
      issues considers the main pathways of interest in drug innovation and the
      elucidation of new targets for the future compounds. As well as their symptomatic
      effects on the different components of cognition, drugs should be neuroprotective
      and limit the lesions documented in Alzheimer's disease, with the aim of
      progressing far beyond the amyloid hypothesis (immunisation, beta-sheet breakers,
      secretase inhibitors). The field of excitotoxicity (which is mainly glutamate
      dependent) appears fruitful, because of the possibility of pharmacological
      intervention at the different steps in the excitotoxic process. All the new
      directions presented in this article support the concept of true disease
      modifying agents. In conclusion, this prospective review should be considered as
      a guide in fostering drug innovation in Alzheimer's disease and related disorders
      and should help to decrease the gap existing between neuroscience and
      therapeutics.

PMID- 15969314
TI  - [Quality of medical order writing in general practice facilities (Sousse,
      Tunisia)].
AB  - BACKGROUND: A medical order is a medical and legal document; careful writing of
      this document enables the reduction of many therapeutic errors. OBJECTIVE: The
      objective of this study was to evaluate the quality of order writing in Tunisian
      primary healthcare centres. METHODS: This was a transversal descriptive survey of
      2586 medical orders. The quality of the writing was assessed using two
      parameters: its legibility and the information delivered in it. RESULTS: Among
      the main results, 36% of orders contained at least 50% of the items retained, 25%
      of orders were completely illegible, and the quality of writing was considered
      good in 14% of cases. DISCUSSION: The study showed that hand-written orders in
      primary healthcare are far from complying with the medico-legal requirements. The
      teaching of order-writing technique and its computerisation are needed to improve
      the quality of medical prescribing.

PMID- 15969315
TI  - [Is fibrinogen a predictor or a marker of the risk of cardiovascular events?].
AB  - Most cardiovascular events result from a thrombotic complication of an
      atherosclerotic lesion. Inflammation plays a central role in both the
      pathogenesis of atherosclerosis and the progression of its complications
      (especially plaque rupture). Fibrinogen, on the one hand a marker of inflammation
      and on the other a major determinant in thrombosis and haemorrheology, plays a
      central role in atherosclerosis and its thrombotic complications. The clinical
      data are in agreement with epidemiological data, and show that increased plasma
      fibrinogen levels (compared with values in paired controls) are predictive of the
      risk of cardiovascular events - both primary cardiovascular events in the general
      population and recurrence in patients. Determining the plasma fibrinogen level in
      terms of genetic predisposition and environmental factors provides a good example
      of the interrelationship between genes and the environment. It must be recognised
      that a minimal increase in the fibrinogen level (within the plasma reference
      values) is an indicator of a significantly increased risk. This shows why
      epidemiological data are not useful for determining cardiovascular risk in
      individual patients in daily clinical practice (with the exception of the very
      high levels that are infrequently observed).

PMID- 15969316
TI  - [Besides fibrinogen, are haemostatic, coagulation and/or fibrinolytic parameters
      predictors or markers of the risk of cardiovascular events?].
AB  - Most cardiovascular events result from a thrombotic complication of
      atherosclerotic lesions. In arterial vessels such as the coronary bed, an
      interrelationship of haemostatic, coagulation and fibrinolytic factors is
      implicated. While it can be demonstrated that fibrinogen is a risk factor/marker,
      the role of other factors is not well established. Under arterial flow
      conditions, platelets are predominantly involved in the thrombotic reaction. Yet,
      apart from a large increase in the platelet count, the involvement of platelet
      parameters in cardiovascular risk is not clearly evident. The lack of definitive
      platelet markers is at least partly due to the difficulty of studying platelet
      function ex vivo. Several polymorphisms of platelet glycoproteins carrying a
      moderate increase in risk have been reported, but only in younger patients. One
      potentially important factor for coagulation is the fibrin structure, which is
      dependent on fibrinogen, the rate of thrombin generation, the activity of factor
      XIII and the interrelationship of the cells concerned, all of which act on its
      sensitivity to thrombosis. Coagulation factors largely affect the rate of
      thrombin generation. The activity of the fibrinolytic system (and principally any
      deficiency) has a role in the cardiovascular risk. General markers of
      cardiovascular risk such as D-dimers are potentially useful, but they increase
      with thrombin generation and are decreased by a deficiency in fibrinolysis.
      Furthermore, possibly because they are not indicative of the fibrin structure,
      they are poorly correlated with clinical events. The poor significance of the
      available haemostatic, coagulation and/or fibrinolytic parameters is probably due
      to their lack of representativeness, since haemostatic, coagulation and
      fibrinolytic systems are all involved in the thrombotic response (and some in
      atherogenesis itself). Atherogenesis is a multifactorial process and numerous
      moderate risk factors act in association. Better predictability of the
      haemostatic tests would probably result from both the design of more
      representative tests and the evaluation of multiple parameters, and would lead to
      the definition of a risk score. Technological advances will make this possible.

PMID- 15969317
TI  - [Assessment of the quality of oral anticoagulation management in patients
      admitted to Amiens University Hospital].
AB  - BACKGROUND: Excessive or insufficient anticoagulation therapy and its associated
      risks are of major concern in patients receiving oral anticoagulants. Such
      complications can be avoided by more rigorous management. OBJECTIVE: The aim of
      our study was to evaluate those patients receiving oral anticoagulant therapy on
      the day of hospitalisation among all patients admitted to the Amiens University
      Hospital during 14 days. METHODS: We evaluated the quality of management of the
      treatment in these patients, taking into account the international normalised
      ratio (INR), as well as important parameters such as the summary of the product
      characteristics (SPCs), drug interactions, and the level of knowledge of
      anticoagulant treatment by the patients themselves (questionnaire). RESULTS: Of
      the 2498 adult patients hospitalised, 86 patients (30 female and 56 male aged
      between 26 and 95 years [mean 70 years]) treated with oral anticoagulants were
      evaluated. At admission, seven cases of haemorrhage and two of thrombosis were
      registered. One drug-related death occurred and one patient had sequelae. In
      17.5% of the cases, the prescription was not fully in agreement with the SPCs.
      This percentage increased to 67% for patients with adverse effects. In 41% of the
      patients, the INR was outside the therapeutic zone. The dosage regimen was too
      complex in 11% of cases. Six drug combinations were labelled as not recommended
      in the SPCs: four with aspirin <3 g/day and two with nonsteroidal anti
      inflammatory drugs. The analysis of questionnaires showed that patients had
      insufficient knowledge of their treatment: only 16 of 66 knew the risks resulting
      from overdose or an insufficient dose of the anticoagulant drug, 25 of 66 knew
      that anticoagulation induced by the treatment can be influenced by food, 10 of 66
      knew the therapeutic range of the INR appropriate for them, and 8 of 66 knew that
      intramuscular injections were prohibited. CONCLUSIONS: These data confirm that
      anticoagulant treatment needs to be more strictly controlled in order to avoid
      adverse effects. Risks are probably underestimated by physicians. Information
      given to patients seems insufficient or unsuitable (too complex).

PMID- 15969318
TI  - [Study over 10 years of 622 protocols receiving unfavourable reports from 19
      research ethics committees].
AB  - OBJECTIVE: The aim of this study was to analyse the nature of applications and
      the criteria for their negative evaluation by 19 ethics committees for the
      protection of human subjects participating in biomedical research, the French
      CCPPRB. METHODOLOGY: The committees distinguished between negative opinions that
      were given from the start of the applications or after amendments were made, and
      between lost protocols (no answer within more than 1 year) or protocols that were
      outside of the framework of the Huriet-Serusclat law. The opinions were analysed
      by an independent observer over a period of 10 years. RESULTS: Few protocols
      (1.3% of the total number of files) are rejected on the basis of scientific and
      ethical criteria. Traceability is a significant problem, which obstructed the
      study of lost protocols and amendments. For protocols not covered by the law, the
      committees already work in accordance with the European directive recommending
      the exclusion of studies consisting only of routine medical procedures.

PMID- 15969319
TI  - Bioequivalence assessment of two enteric-coated aspirin brands, Nu-Seals and
      Loprin, after a single oral dose of 150 mg in healthy male adults.
AB  - AIM: The bioequivalence of aspirin from two enteric-coated brands, Nu-seals and
      Loprin, identified as the reference (R) and test (T) products, respectively, was
      assessed. METHODS: A two-period randomised crossover design with a washout
      interval of 15 days was used in this study. The study results were determined in
      16 healthy volunteers, all males with ages ranging from 19-28 (23.33 +/- 3.74)
      years and bodyweights of 52-92 (65.89 +/- 11.39) kg. After oral ingestion of
      150mg of the either brand with 200 mL of water, serial blood samples were
      obtained over a period of 24 hours. Plasma, harvested from blood was analysed for
      the concentration of salicylic acid, a deacetylated metabolite of aspirin, by a
      validated high performance liquid chromatography (HPLC) method. Pharmacokinetic
      parameters were determined for both formulations by an interactive computer
      assisted PK II procedure. A general linear model for repeated measures and 90%
      confidence intervals (CI) was employed to assess the sequence of treatment
      effects and to exclude differences between the parameters due to the product and
      period of administration, respectively. RESULTS: The observed 90% CI ratios
      (Loprin/Nu-seals) for peak concentration, time to reach the peak and area under
      the plasma-concentration time curve from zero to infinity of 1.03,1.08; 1.04,1.05
      and 1.01,1.15, respectively, were within the bioequivalence range (0.80,1.25)
      stipulated by the US Food and Drug Administration. CONCLUSION: On the basis of
      the findings, the test (Loprin) and reference drug (Nu-seals) were deemed
      bioequivalent.

PMID- 15969321
TI  - Clinical research infrastructures and networks in France: report on the French
      ECRIN workshop.
AB  - A meeting was organised in Paris on 13 September 2004, to provide an in-depth
      description of the state of the art in institutional clinical research
      infrastructures and their environment in France. This meeting was scheduled
      within the ECRIN (European Clinical Research Infrastructures Network) project,
      funded by the European Union (6th Framework Programme). Ten items were addressed:
      (i) centres and networks; (ii) funding and sponsoring of clinical research; (iii)
      ethics; (iv) legislation and regulation; (v) adverse-event reporting and drug
      dispensing; (vi) methodology, data management and data monitoring; (vii) quality
      management and audits; (viii) communication with investigators, sponsors and
      participants; (ix) transparency and registration of clinical studies; and (x)
      education and careers. This description, together with parallel workshops held in
      other countries using a similar pattern, helped prepare a comparative analysis
      enabling better identification of the bottlenecks for multinational research in
      Europe, and define the most relevant approaches to harmonisation and the services
      required to support the role of sponsors in transnational studies.

PMID- 15969320
TI  - [Assessment of renal abnormalities in 107 HIV patients treated with tenofovir].
AB  - OBJECTIVES: The objectives of our study were to assess frequency, severity and
      outcome of renal abnormalities, as well as to determine the risk of developing
      hypophosphataemia in HIV-infected patients receiving tenofovir. METHODS: An
      observational study was conducted in real-life conditions, during a 6-month
      period, in 107 HIV patients receiving tenofovir. RESULTS: Mild-to-moderate
      hypophosphataemia (<0.77 mmol/L) occurred during follow-up, at least once in 43%
      of patients and at least twice in 27%. Antiretroviral therapy including ritonavir
      + lopinavir was significantly associated with the occurrence of hypophosphataemia
      (relative risk = 2.6; p = 0.03). Frequency of abnormal proteinuria was 22%.
      CONCLUSION: Creatinine clearance, phosphataemia, proteinuria and glycosuria
      should be closely monitored in patients receiving tenofovir therapy.

PMID- 15969322
TI  - Biogenic amines in meat and meat products.
AB  - It has been recognized for some time that biogenic amines occur in a wide range
      of foods, among them meat and meat products. Meat is an important component of
      the diet in developed countries. The presence of these amines in food is of
      interest for two reasons: firstly, for toxicological reasons, in the sense that
      high levels of dietary biogenic amines can be toxic for certain consumers, and
      secondly, for their role as possible quality indicators. Based on these two
      premises, the present article offers a new analysis on aspects of toxicology and
      on the use of biogenic amines as a quality control method, as well as on their
      presence in meat and meat products. The article focuses particularly on factors
      affecting the production of biogenic amines, with reference to various parameters
      relating to microorganisms, meat raw materials, and processing conditions. A
      better understanding of the factors determining their formation (i.e.,
      microorganisms, raw materials used, and technological processes applied) and
      their effects could lead to ways of controlling their production, limiting their
      presence in the end product, and hence, rendering them less toxic.

PMID- 15969323
TI  - Evaluation of performance measurement instruments on their use for food quality
      systems.
AB  - Due to regular challenges of food safety, consumers put high demands on the
      performance of food quality systems. To deal with these requirements, food
      manufacturers need effective quality management. Performance of food quality
      systems can be partly realized by quality assurance systems, such as HACCP
      (hazard analysis and critical control point), ISO (international organization for
      standardization), and BRC (british retail consortium). However, it is still
      unknown to what extent these systems factually contribute to the realization of
      quality in the wider sense. Therefore, an instrument is needed that measures the
      effectiveness of quality systems. This article describes the evaluation of
      instruments on their suitability for the development of a diagnostic instrument
      that measures the effectiveness of food quality systems. For this evaluation,
      perspectives of quality, typical characteristics of agrifood production,
      quantification, and performance measurement of quality management were studied.
      Instruments that measure the performance of both quality management and
      production quality were identified and evaluated on the basis of the defined
      criteria. The criteria for the performance of production quality were 6 quality
      dimensions, i.e., product quality, availability, costs,flexibility, reliability,
      and service. The criteria for performance of quality management were analyses of
      the relationships between quality management, context of the organization, and
      production quality, a normative procedure, validation, applicability,
      classification, and a process approach. Finally, for the final instrument, the
      evaluation resulted in an integrated approach i.e., a technomanagerial approach,
      and 3 suitable instruments i.e., Wageningen Management Approach, Extended Quality
      Triangle, and the quality concept of Noori and Radford.

PMID- 15969324
TI  - The cost and benefit of Listeria monocytogenes food safety measures.
AB  - The objectives of this study were to evaluate economic techniques used to
      determine the cost and benefit of Listeria monocytogenes control and to estimate
      the economic optimum of L. monocytogenes food safety measures. The level of food
      safety measures is optimal if marginal benefit and marginal cost equate.
      Estimates of benefit and cost of L. monocytogenes food safety measures, from
      available published literature, are derived from different methods of economic
      analysis (willingness to pay, cost of illness, cost function, and event study
      methods). The estimated annual benefit and cost of L. monocytogenes food safety
      measures range from $2.3 billion to $22 billion and from $.01 billion to $2.4
      billion, respectively. The estimated marginal benefit exceeds the estimated
      marginal cost, which implies that more food safety measures are warranted before
      the optimal level of L. monocytogenes food safety can be reached. However, due to
      considerable lack of data, the optimal level of L. monocytogenes food safety
      measures could not be estimated. When better data become available, this study
      can serve as a template for estimating the optimal level of food safety. The
      understanding of the economic optimum of food safety level will contribute to
      designing a control program that is economical and acceptable for US society.

PMID- 15969325
TI  - Electrodialytic phenomena and their applications in the dairy industry: a review.
AB  - Electrodialysis (ED) is an electrochemical separation process by which
      electrically-charged species are transported from one solution to another ED is a
      combined method of dialysis and electrolysis and can be performed with two main
      cell types: multi-membrane cells for dilution-concentration and water
      dissociation applications (membrane phenomena), and electrolysis cells for redox
      reactions (electrode phenomena). The dilution-concentration principle
      applications in the dairy industry consist mainly of the demineralization of milk
      or milk by-products. The use of ED with monopolar membrane for protein separation
      and acid caseinate production, and in bioreactors for organic acid production, is
      also studied in the dairy industry. The interest of ED as a membrane process has
      been triggered recently by the development of a new membrane type, bipolar
      membrane. This membrane carries out the dissociation of water molecules. ED with
      bipolar membranes was applied very recently to the production of lactic acid from
      whey product fermentation, production of caseinates, and fractionation of whey
      proteins. Two principle applications of electrode reactions were published:
      electrochemical coagulation (EC) to precipitate milk proteins, and
      electroreduction for the reduction of disulfide bonds in the proteins. It appears
      in this article that processes using membrane phenomena are more numerous and
      developed than electrolytic applications. This is the composition of milk and the
      lack of knowledge of redox reactions of the different food compounds that limit
      the applications and the development of electrolytic phenomena. Electrodialytic
      phenomena present a great potential for application in the dairy industry, and
      more generally, in the food industry; many of these applications have to be
      discovered.

PMID- 15969326
TI  - Effect of surfactant gels on dough rheological characteristics and quality of
      bread.
AB  - Sodium stearoyl-2-lactylate (SSL), diacetyl tartaric acid esters of monoglyceride
      (DATEM), glycerol monostearate (GMS), and distilled glycerol monostearate (DGMS)
      surfactant gels were made with water and varying shortening contents. The effect
      of these gels on dough rheological characteristics and quality of bread was
      investigated. Overall, the surfactant gels improved the farinograph and
      extensograph characteristics of wheat flour, but the improvement reduced to some
      extent with the presence of shortening in the gels. Alveograph data indicated
      that dough properties improved with the addition of surfactant gels. Shortening
      in gels showed varying influence on the dough alveograph properties of wheat
      flour. The results indicated that the surfactant gels changed the rapid visco
      analyzer characteristics of wheat flour, and the presence of shortening in gels
      further altered the characteristics. All surfactant gels improved the volume,
      specific volume, texture, and overall quality scores of bread, but the
      improvement varied for different surfactants. By increasing the addition of
      shortening in gels, though the quality characteristics further improved, the
      response to surfactants reduced by increasing shortening content.

PMID- 15969327
TI  - Lactose: the milk sugar from a biotechnological perspective.
AB  - Lactose is a very important sugar because of its abundance in the milk of humans
      and domestic animals. Lactose is a valuable asset as a basic nutrient and the
      main substrate in fermentative processes that led to the production of fermented
      milk products, such as yogurt and kefir. In some instances, lactose also can be a
      problem as the causative agent of some diseases, such as lactose intolerance and
      galactosemia, or for being a by-product generated in huge amounts by the cheese
      industry. The study of the biochemical reactions leading to the synthesis and
      assimilation of lactose has provided valuable models for the understanding of
      biosynthetic and catabolic processes. Lactose-hydrolyzing enzymes are
      structurally and phylogenetically related to different types of beta
      galactosidases and bacterial cellobiases involved in the enzymatic degradation of
      cellulose. Biotransformation of lactose, by either enzymatic or fermentative
      procedures, is important for different types of industrial applications in dairy
      and pharmaceutical industries.

PMID- 15969328
TI  - Stability and synergistic effect of antioxidative properties of lycopene and
      other active components.

PMID- 15969330
TI  - Unfortunately, we were unable to fund this proposal...

PMID- 15969329
TI  - Dietary antioxidant compounds and liver health.
AB  - Chronic liver damage is a widespread pathology characterized by a progressive
      evolution from steatosis to chronic hepatitis, fibrosis, cirrhosis, and
      hepatocellular carcinoma. As the oxidative stress plays a central role in liver
      diseases pathogenesis and progression, the use of antioxidants have been proposed
      as therapeutic agents, as well as drug coadjuvants, to counteract liver damage.
      In this work in vitro and in vivo studies, with emphasis on humans and animals
      experiments, have been considered and reviewed according to antioxidant
      typologies. Great differences emerge as far as ingested doses, bioavailability
      and liver ability to accumulate the various compounds. Results available up to
      now suggest that lycopene-rich foods could be proposed in therapeutic treatment
      of some liver pathologies. On the other hand contradictory results have been
      obtained with alpha-tocopherol, beta-carotene and trans-resveratrol. Quercetin,
      silymarin, esculetin and thyme and rosemary among phenolic compounds need further
      studies.

PMID- 15969331
TI  - Baccalaureate-linked oncology nursing education: McMaster University's Paediatric
      and Adult Oncology Nursing Program.
AB  - For new nursing graduates prepared as generalists, the transition from student to
      graduate and from new generalist graduate to experienced specialized nurse can be
      very anxiety-provoking. This paper discusses one program, the Oncology Nursing
      Program, McMaster University, designed for nurses working along the cancer
      continuum. Proposed by oncology nurses seeking baccalaureate-linked specialty
      education, the year-long program has now been in existence for 10 years. A cadre
      of nearly 200 graduates affirm that specialized education influences direct
      patient care, health care team membership, professional and personal development.

PMID- 15969332
TI  - Are advanced practice nurses (APNs) here to stay? The APN in the oncology
      setting.

PMID- 15969333
TI  - Travelling for radiation cancer treatment: patient satisfaction.
AB  - This study was conducted for the purpose of describing cancer patients'
      satisfaction with their care when they had to travel unexpectedly away from home
      for treatment. Ontario initiated a rereferral program for cancer patients who
      needed radiation therapy when the waiting lists in southern Ontario became
      lengthy. Patients travelled to the United States or northern Ontario for their
      care. A standardized survey containing 25 items with five-point Likert scale
      responses was mailed to all patients who participated in the rereferral program,
      following completion of their treatment. Items covered patient experiences before
      leaving home, in preparing for travel, and staying at the cancer facilities away
      from home. A total of 466 (55.8%) patients returned the survey. Overall, patients
      were satisfied with their care. However, there were a number of areas identified
      by patients where improvements could be made. These areas included access to
      support prior to leaving home, access to information about supportive care
      services while away from home, and sensitivity to personal needs in making
      arrangements for travel. Provision of information and support are important to
      cancer patients having to travel for cancer treatment.

PMID- 15969334
TI  - Palliative nurses' interest group.

PMID- 15969335
TI  - [Modern aspects of systematics].

PMID- 15969336
TI  - [Hexapoda phylogeny: implications for an aquatic origin hypothesis].
AB  - Emergence from an aquatic environment to the land is one of the major
      evolutionary transitions within the arthropods. It is often considered that the
      first hexapods, and especially the first Collembola, went from the sea through
      intermediate freshwater environments to colonize fully terrestrial ecosystems. To
      understand the ancestral ecology of hexapods, a phylogenetic framework is used.
      By mapping ecological attributes onto the phylogeny, it is shown that hexapods
      colonized terrestrial environments directly from marine environment without a
      transition through freshwater. An edaphic life-style is the basal state for
      Collembola and more generally for hexapods as a whole. Aquatic ecology is
      inferred to be a secondary change that occurred several times independently,
      particularly in some group of Collembola and Pterygota. The answer is ambiguous
      for Pterygota, whether the first Pterygota had aquatic larvae and reversed toward
      fully terrestrial in Neoptera, or aquatic larvae appeared independently in
      Odonata and Ephemeroptera. Subsequently, aquatic larvae were secondarily acquired
      in various groups independently (e.g. Plecoptera, Trichoptera, Coleoptera).

PMID- 15969337
TI  - [Return of the prodigal bandwagon: what molecular phylogenies and databasing can
      bring to compared anatomy (the example of teleosts)].
AB  - Molecular and morphological aspects are traditionally opposed in life sciences.
      Systematics, however, has long used molecular tools for evolutionary purposes and
      might be the place to unify those two elements of biology, even though up until
      recently, such methodologies were incompatible and opposed. Morphological studies
      suffer from a lesser recognition and a largely inferior access to credits and
      renewal of personnel, because of the length of time and level of specialization
      required to produce morpho-anatomy based work. Databasing might be a way to
      simplify and speed up morphological studies. The use of databases is spreading in
      systematics, from bibliography to collection catalogs and localisation, to
      sequence banks. The example of Acanthomorpha examplifies this with the
      construction of a database gathering bibliographical and anatomical data so as to
      avoid repeating previous work. Molecular phylogenies cannot be explored alone;
      they need to be compared with morphological analyses.

PMID- 15969338
TI  - [Contribution of molecular phylogeny and morphometrics to the systematics of
      African elephants].
AB  - African elephants are conventionally classified as a single species: Loxodonta
      africana (Blumenbach 1797). However, the discovery in 1900 of a smaller form of
      the African elephant, spread throughout the equatorial belt of this land, has
      given rise to a debate over the relevance of a second species of elephant in
      Africa. The twentieth century has not provided any definite answer to this
      question. Actually, recent molecular analyses have sustained this issue by
      advocating either a division of forest elephants into a valid species, or their
      inclusion as a subspecies of L. africana. Our work initiated at the National
      Museum of Natural History of Paris provides new molecular (mitochondrial) and
      morphological (and morphometrical) evidence making it possible to propose a
      comprehensive phylogenetic hypothesis. It appears that there is no conclusive
      argument to keep forest elephants (cyclotis form) and savannah elephants
      (africana form) apart in two distinct species. A high level of mitochondrial
      introgression between the two forms, as well as a continuum in the morphology of
      the skulls of the two morphotypes rather suggests that, despite an ancient
      division, these two taxa freely interbreed wherever their ranges intersect. We
      thus adopt a conservative systematic position in considering these two forms as
      two subspecies, respectively: L. africana africana, the savannah elephant, and L.
      africana cyclotis, the forest elephant. We finally discuss the conservation topic
      in the light of this systematic framework.

PMID- 15969339
TI  - [Recent rhinos do not lack character(s): neither do fossil rhinos!].
AB  - Concepts, methods, and interest of phylogenetic reconstruction are briefly
      examined. As large data sets are considered and refutable results are proposed,
      there is no need to use the argument of authority concerning relationships
      between taxons. Cladistic analysis in vertebrate palaeontology has gained
      considerable strength in the last decade, based on sets of hundreds of anatomical
      characters. One example is selected, which concerns the rhino family, i.e.
      rhinocerotids. Although underrepresented in recent times, these perissodactyl
      mammals flourished throughout the Cenozoicera (4 recent genera vs. 50 fossil
      genera). The main results of a recent cladistic analysis of elasmotheriine
      rhinocerotids, based on 282 anatomical characters, are listed. Such results
      concern phylogenetics (monophyly of both elasmotheriines and recent rhinos;
      branching of elasmotheriines among rhinocerotids) and methodology (definition of
      a "branching group"; location and processing of homoplasy; influence of taxonomic
      sampling). The implications are both biostratigraphical and palaeobiogeographical
      (evolution of the diet and spatial distribution; intercontinental dispersals;
      ghost lineages and heuristic use of the phylogenetic tree). Finally, forthcoming
      developments of the available data set for rhinocerotids are examined:
      controversial phylogenetic relationships among recent rhinos will be refined
      (thanks to close extinct taxa) and an exhaustive phylogeny of fossil and recent
      rhinocerotids will be reconstructed (54 genera).

PMID- 15969340
TI  - [Cadherins: structure and signalisation protein of cell-cell junctions.
      Introduction and conclusions].
AB  - Cadherin is a super family of genes, with at least 80 members. These members
      include classic cadherins, desmogleins, desmocollins, protocadherins, CNRs, Fats,
      seven-pass transmembrane cadherins and Ret tyrosine kinase. The repeated EC
      extracellular domains (N-terminal domain) are common to the family members and
      ensure cell adherence in a calcium dependant mechanism. The cadherins are
      expressed from amoebae to mammals. The biological complexity of cadherins is
      expressed at different levels, multigenic family and multiple functions in
      different tissues leading to use different methodological approaches. All the
      talks in this session broach in a promising aspect in the field of the basic
      comprehension of cell adhesion (R. M. Mege), at the molecular level (H. Feracci),
      physiological homeostasis of gut (S. Thenet), cell lineage (V. Delmas) or cancer
      transformation (L. Larue).

PMID- 15969341
TI  - [Molecular aspects of cadherin-mediated cell adhesion: the first moments of the
      interaction].
AB  - Cadherins play a major role in the development and maintenance of all solid
      tissues. These transmembrane glycoproteins are responsible for calcium-dependent
      homophilic cell interactions. Recently, many different experimental approaches
      have been used to untangle the molecular basis of cadherin-mediated adherence.
      Various models have been suggested, particularly from high-resolution structures.
      Whilst the adherence mechanism is still under controversy, it is widely accepted
      that the specificity of the adherent interaction is localized to the N-terminal
      domain. New biophysical techniques together with biological approaches will allow
      a better understanding of how cadherins regulate cell-cell adherence. Integrating
      kinetics properties of cadherin interaction at the single molecule level has led
      to a greater understanding of cadherin molecular regulations.

PMID- 15969342
TI  - [Regulation of cell adhesion by the cadherin cytoplasmic domain].
AB  - Juxtacrine cell interactions associated to cadherin-mediated cell-cell adhesion
      play a major role in the organization and homeostasis of tissues. Here, we review
      the intracellular molecules and regulations controlling the formation of cell
      cell contacts initiated by homophilic interactions of cadherin ectodomain. These
      regulations involve proteins associated to cadherin cytoplasmic tail, named
      catenins, their association to the actin cytoskeleton and the stability of these
      complexes at the cell membrane. The underlying molecular mechanisms, which
      participate in the formation of dynamic cell-cell contacts, are intensively
      investigated.

PMID- 15969343
TI  - [Regulation of E-cadherin by the Akt protein kinase B].
AB  - E-cadherin is a cell adhesion molecule that is present in most normal epithelial
      cells. During malignant transformation, the expression of E-cadherin is
      frequently repressed. This protein is considered as a tumor-suppressor. The
      oncogenic form of Akt, a serine-threonine kinase, is multifunctionnal. One of its
      function is to induce the transcriptional repression of E-cadherin. This
      transcriptional repression induces cellular responses, epithelial cells becoming
      mesenchymal and invasive. At the molecular level, cells expressing a constitutive
      active form of Akt express also a transcription factor, Snail, known to repress
      the expression of E-cadherin.

PMID- 15969344
TI  - [Control of the survival/apoptosis balance by E-cadherin: role in enterocyte
      anoikis].
AB  - Cadherins are transmembrane glycoproteins involved in cell-cell adherence. Recent
      developments indicate that classical cadherins may act as adherence-activated
      signaling receptors. Here, we review recent data from the literature concerning
      the role of classical cadherins in the control of cell survival and the signaling
      pathways involved. We focus on the fate and the role of E-cadherin, the main
      classical cadherin expressed in epithelial cells, in the cell death program
      triggered in enterocytes by loss of anchorage from the extracellular matrix
      (anoikis). These data open new perspectives on the key role of this protein,
      which is dysregulated in most carcinoma and is considered as a tumour-suppressor.

PMID- 15969345
TI  - [Cadherins in the mammary gland and the melanocyte lineage].
AB  - Cadherins are transmembrane glycoproteins involved in cell-cell adhesion,
      signalling, proliferation and differentiation. In this review, we have focused
      upon in vivo cadherin expression and function in two different biological
      systems, the mammary gland epithelium and the melanocyte lineage. Development of
      the mammary gland represents a paradigm of in situ epithelial differentiation and
      the melanocyte lineage of a model of non-epithelial (or mesenchymal) cell
      differentiation where cells migrate extensively from their site of origin towards
      the skin compartment. In the mammary epithelium, the predominantly expressed
      cadherin is E-cadherin, a cell surface molecule that directs morphogenesis and
      maintenance of the epithelial structure. In the melanocyte lineage, the
      expression of a number of cadherins is strictly spatiotemporally regulated during
      development and adult life. The specific functions mediated by this very dynamic
      cadherin expression are not yet known and their characterisation represents a
      challenge for the future.

PMID- 15969346
TI  - [Structure and evolution of transposable elements].

PMID- 15969347
TI  - [Retroviral inheritance in man].
AB  - The data provided by the sequencing of the human genome showed that retroviral
      like elements constituted approximately 8 % of the euchromatin. The origin of
      these elements, their propagation leading to an organization in families, their
      genetic structure and the identification of the fonctional domains of the
      components of these elements are described. Placenta is used as a model to
      illustrate the physiological involvement of HERVs. Transcriptional regulatory
      element (LTR) functions and the putative implication of retroviral proteins in
      resistance to infection, immunosuppression, and cellular differentiation are
      clarified. The data implicating the envelope encoded by the ERVWE1 locus of the
      HERV-W family in the fusion process, leading to syncytiotrophoblast formation, is
      analysed. The putative pathological effect of HERVs is illustrated by the
      expression of the HERV-K superfamily in cancer. More precisely, the association
      between the Rec regulatory protein encoded by HERV-K(HML-2) and testicular
      tumorigenesis is developed. Whether HERVs are triggers or markers in other
      physiopathological contexts is discussed. To conclude, the dual benefit-hazard
      underlying the acquisition/propagation of HERVs is examined with respect to
      species evolution, considering the multicopy trait of HERV families and the
      mainly multi-factorial aspect of autoimmune diseases and cancers.

PMID- 15969348
TI  - [The influence of transposable elements on genome size].
AB  - Genome size displays an important variability between species without any direct
      link to complexity. This paradox, so-called "C value paradox", now becomes
      understood as resulting from a differential abundance of numerous repeated
      sequences, among which transposable elements. Genomes indeed contain a important
      proportion of such sequences (95 % of DNA in man, about 45 % of which are
      transposable elements, up to 99 % of DNA in some plants). While most
      investigations until now are focalized on genes or coding sequences, which thus
      represent a small part of the genome, more attention now is dedicated on so
      called non-coding sequences. Transposable elements, which are capable of moving
      around in genomes, inducing mutations, chromosomal rearrangements, gene
      expression regulations, thus appear as major actors in diversity and evolution.
      We present here a brief review of the most prominent acquisition in this
      expanding domain.

PMID- 15969349
TI  - [Genomic instability associated with human LINE-1 retrotransposition].
AB  - LINE-1 (L1) retrotransposon accounts for approximately 17 % of the human genome.
      Because of the great number of identical copies, L1 can be implicated in genomic
      rearrangements associated with events of homologous recombination between
      heterologous sites. Moreover, even if the vast majority of the L1 elements are
      inactive, some are still able to mobilize themselves by retrotransposition. Thus,
      L1 is regarded as an insertional mutagenic agent. Moreover, recent works have
      shown that active retrotransposons were able to mobilize other sequences to
      generate retro-pseudogenes or to amplify other repeated sequences. Finally, L1
      has been associated recently with new genomic rearrangements generated upon
      insertions such as large genomic deletions. L1 then can be considered as a major
      factor that has affected and shaped the human genome through several mechanisms.

PMID- 15969350
TI  - [Stress activation and genomic impact of plant retrotransposons].
AB  - Retrotransposons are mobile genetic elements that amplify via reverse
      transcription of an RNA intermediate. They insert at different positions in host
      genomes, can be amplified to high copy number and are an important source of
      genetic diversity. The tobacco TntlA retrotransposon is activated by stresses of
      pathogen origin, and regulatory sequences involved in this activation are similar
      to those of various stress responsive plant genes. Tnt1A belongs to an ancient
      family present in various Solanaceous species, and composed of populations of
      closely related elements that differ in their expression conditions. This
      expression is often observed in response to stress, but with specificities that
      differ sensibly for each population, possibly refecting an adaptative response of
      ancestral populations to different stimuli, during the radiation of Solanaceous
      species and genera. Microbial factors efficiently stimulate Tnt1A amplification,
      reinforcing the hypothesis that environmental challenges can generate genetic
      modifications. In addition, TntlA transposition preferentially targets genic
      regions, suggesting that the activity of transposable elements can modulate genic
      functions and represent a natural source of phenotypic diversity.

PMID- 15969351
TI  - [The biology of conformation in the regulation of the senescent and transformed
      cell phenotypes].
AB  - The cytoskeleton and the cytoplasmic membrane of normal somatic cells are
      modified during proliferation. The loss of the division potential during serial
      proliferation is due in part to these structural modifications that induce a
      decline in the cell conformational flexibility. During viral transformation, the
      changes in the cytoskeleton and in the affinity of the cell to its matrix and to
      neighboring cells increase the cell migratory capability, maintaining the
      conformation flexibility needed for the initiation of the division cycle. We
      could modulate cell proliferation, transformed phenotype, and differentiation by
      changing the electric charge of a substratum. Results support the view that the
      biology of conformation is crucial for the expression of these cell properties.

PMID- 15969352
TI  - Development and validation of the Subjective Awareness of Neuropsychological
      Deficits Questionnaire for Children (SAND-C).
AB  - Although lowered awareness of abilities has been associated with poorer outcome
      in adults with neurological compromise, a dearth of research exists examining
      whether lowered awareness exists in younger populations. Using findings from
      recent literature and expert opinion, a 47-item Subjective Awareness of
      Neuropsychological Deficits Questionnaire for Children (SAND-C) was created to
      assess awareness of cognitive functioning in 6 domains (attention, psychomotor,
      visual-spatial, language, memory, and executive functioning). Confirmatory factor
      analysis (CFA) of the SAND-C was conducted on a sample consisting of 365 healthy
      children and 48 children with epilepsy. The SAND-C was found to have strong
      reliability. Factor analysis confirmed the a priori 6 factor model, but the 6
      factor model was only marginally better than a more parsimonious 1-factor
      solution. Post-hoc exploratory factor analyses indicate that the SAND-C may
      measure more constructs for adolescents than for younger children. The difference
      between younger and older children may reflect developmental changes in
      metacognitive awareness and abstraction about their own abilities.

PMID- 15969353
TI  - Does methylphenidate improve inhibition and other cognitive abilities in adults
      with childhood-onset ADHD?
AB  - We examined the effect of methylphenidate (Mph) on inhibition and several other
      cognitive abilities in 43 adults with Attention Deficit Hyperactivity Disorder
      (ADHD) by use of Conners' Continuous Performance Test (CPT) and the Change Task
      (ChT), an extension of the Stop Signal Test (SST). In a double blind, cross-over,
      placebo controlled study with Mph, tests were administered during the third week
      of individually titrated treatment with Mph (maximum dose 1 mg / kg / day) and
      during the third week of treatment with placebo. We established large medication
      effects for commission errors, standard error of mean reaction time, and
      attentiveness on the CPT, as well as moderate medication effects for mean
      reaction time on the CPT and response re-engagement speed on the ChT. For Stop
      Signal Reaction Time (SSRT) on the ChT, we also established large effects of Mph,
      but only in a group of participants who showed slow SSRTs on placebo. Mph indeed
      ameliorates inhibition, which is the core problem of ADHD, and certain other
      cognitive abilities in adults with ADHD.

PMID- 15969354
TI  - Neuropsychological impairment as a consequence of football (soccer) play and
      football heading: preliminary analyses and report on university footballers.
AB  - Previous research has claimed neuropsychological impairment occurs as a result of
      professional and amateur football play, and, specifically, football heading.
      However, much of this research exhibits substantial methodological problems. By
      investigating less committed amateur level footballers, the current study sought
      to gain some insight into the developmental history of any neuropsychological
      consequences of football play. University football, rugby and noncontact sports
      players were compared on a range of biographical and neuropsychological test
      variables. While playing their chosen sports, rugby players sustained many more
      head injuries than footballers and noncontact sportsmen, but footballers did not
      sustain significantly more head injuries than noncontact sportsmen. The number of
      head injuries sustained predicted Trails B and TAP Divided Attention latencies in
      a positive fashion. After controlling for the number of head injuries sustained,
      sport group effects were detected with TAP Divided Attention accuracy scores,
      with footballers exhibiting poorest performance. After controlling for the number
      of head injuries sustained, the total amount of heading done by footballers
      predicted the number of Wisconsin Card Sorting category shifts in a negative
      fashion. Nevertheless, over interpretation of all of these results should be
      resisted because of the exploratory nature of the analyses and the possibility
      that the sport groups may differ in ways other than just the nature of their
      sports activities.

PMID- 15969355
TI  - Face emotion perception and executive functioning deficits in depression.
AB  - Frontal, limbic and temporal regions of the brain important in emotion perception
      and executive functioning also have been implicated in the etiology and
      maintenance of depression; yet, the relationships among these topics remain
      poorly understood. The present study evaluated emotion perception and executive
      functioning among 21 depressed women and 20 nondepressed women controls.
      Depressed women performed significantly worse than controls in emotion perception
      accuracy and in inhibitory control, an aspect of executive functioning, whereas
      the groups did not differ in other cognitive tests assessing memory, visual
      spatial, motor, and attention skills. The findings suggest that emotion
      perception and executive functioning are disproportionately negatively affected
      relative to other cognitive functions, even in a high-functioning group of mildly
      depressed women. Measures of emotion perception and executive functioning may be
      of assistance in objectively measuring functional capability of the ventral and
      dorsal neural systems, respectively, as well as in the diagnosis of depression.

PMID- 15969356
TI  - Neuropsychological studies of mild traumatic brain injury: a meta-analytic review
      of research since 1995.
AB  - A meta-analysis conducted by Binder, Rohling and Larrabee established a
      relationship between mild traumatic brain injury (TBI) and small reductions in
      cognitive functioning in individuals assessed more than 3 months post-injury. As
      a follow-up, this study summarized similar research that (1) was published since
      the previous meta-analysis, and (2) included data collected at any stage post
      injury. An extensive literature search revealed 17 suitable studies from which
      effect sizes were aggregated. The overall effect size was g = 0.32, p < .001.
      Speed of processing measures had the largest effect, g = 0.47, p < .001. The
      merging of post-acute effect sizes with those reported in Binder et al.'s review
      yielded a nonsignificant result, g = 0.11. Time since injury was found to be a
      significant moderator variable, with effect sizes tending to zero with increasing
      time post injury.

PMID- 15969357
TI  - Skull fracture during infancy: a five-year follow-up.
AB  - A group of 19 children, who had received a skull fracture during infancy, were
      assessed at least 5 years following injury. The majority of the group (89%) had
      received a mild traumatic brain injury (TBI), with the remaining two (11%) having
      a moderate injury. The neuropsychological, academic, and psychosocial functioning
      of the TBI group was compared to that of 20 orthopedic subjects. The two groups
      were matched on the variables of gender, age, and socio-economic status. The TBI
      group was impaired on tests of visual attention and memory for faces. The two
      groups did not differ significantly on measures of language, sensorimotor
      functions, or visuospatial functioning. There were no statistically significant
      differences between the two groups on academic performance, or parent and teacher
      reports of psychosocial functioning. It is concluded that while there is an
      absence of deficits in the vast majority of functions, skull fracture in infancy
      can result in enduring impairment in specific cognitive skills related to the
      processing of complex nonverbal stimuli.

PMID- 15969358
TI  - Assessment of story comprehension deficits after brain damage.
AB  - A story comprehension task was specifically developed for the clinical diagnosis
      of text comprehension deficits. The performance of 49 healthy control
      participants on qualitatively different Yes/No questions confirmed that both
      salience and explicitness of information had an impact on question difficulty. An
      unselected group of brain damaged patients (n = 96) made more errors,
      particularly on questions about implicit information. The subgroup of patients
      with left-hemispheric vascular aetiology (n = 18) had particular difficulties
      with stated details, patients with right-hemispheric vascular aetiology (n = 12)
      with implicit main ideas, and patients with traumatic brain injury (n = 34) were
      most impaired on implicit information. Correlations with neuropsychological test
      scores also confirmed that the questions successfully tapped different
      subprocesses of comprehension. Performance on implicit main ideas was correlated
      with tests of executive functions, whereas the performance on the other three
      question types was correlated with long-term memory and verbal learning. These
      results suggest that the story comprehension test is a useful diagnostic tool for
      neuropsychological assessment.

PMID- 15969359
TI  - Assessment of knowledge and utilization of safety measures among workers on
      occupational health hazards.

PMID- 15969360
TI  - Consumer's Protection Act--implication on nursing practice.

PMID- 15969361
TI  - Systemic lupus erythematosus--a challenging disease.

PMID- 15969362
TI  - Electrochemically induced and controlled one-step covalent coupling reaction on
      self-assembled monolayers.
AB  - We report on a novel covalent coupling method using electrochemical activation of
      hydroquinone monoester self-assembled monolayers. The reaction generates
      benzoquinone as a good leaving group, followed by nucleophilic acyl substitution
      with a primary amine to form an amide in high yield. The method allows the site
      selective and the reaction-controlled positioning of biotin on the individually
      addressable microelectrode array and, subsequently, density-differentiated
      patterning of streptavidin on the biotin surfaces. Because the electrochemical
      coupling method provides a very rapid, mild, and quantitatively controllable
      reaction pathway for covalent bond formation on organic surfaces, it will be used
      as a versatile molecular anchoring tool in fields such as molecular electronics
      and biochip technology.

PMID- 15969363
TI  - From rolling ball to complete wetting: the dynamic tuning of liquids on
      nanostructured surfaces.
AB  - In this work, for the first time, a dynamic electrical control of the wetting
      behavior of liquids on nanostructured surfaces, which spans the entire possible
      range from the superhydrophobic behavior to nearly complete wetting, has been
      demonstrated. Moreover, this kind of dynamic control was obtained at voltages as
      low as 22 V. We have demonstrated that the liquid droplet on a nanostructured
      surface exhibits sharp transitions between three possible wetting states as a
      function of applied voltage and liquid surface tension. We have examined
      experimentally and theoretically the nature of these transitions. The reported
      results provide novel methods of manipulating liquids at the microscale.

PMID- 15969364
TI  - Highly fluorescent streptavidin-coated CdSe nanoparticles: preparation in water,
      characterization, and micropatterning.
AB  - CdSe quantum dots (QDs) with a high fluorescence quantum yield of 25% and a
      narrow size distribution were synthesized in a single step in water using
      glutathione as a stabilizing molecule. The exceptional optical properties enabled
      for the first time the detection of in-water-prepared single quantum dots at room
      temperature. For application as fluorescent bioanalytical probes, the QDs were
      coated with streptavidin. These QDs self-assemble with high contrast on
      micropatterned biotin while preserving their optical properties and their
      capability to bind in addition biotinylated molecules, a prerequisite for the
      development of novel supramolecular structures and bioassays.

PMID- 15969365
TI  - Membrane dynamics of a myelin-like giant multilamellar vesicle applicable to a
      self-reproducing system.
AB  - A real time observation of a myelin-like giant multilamellar vesicle (mGMV)
      revealed that it divided into relatively small mGMVs when an aqueous solution of
      an electrolyte was added. Furthermore, the mGMV showed a division process
      accompanied by the growth of the dividing mGMVs when a bolaamphiphile which was
      composed of an electrolyte unit and a vesicular amphiphile unit was added. This
      vesicular system can be regarded as a self-reproduction of mGMV, where the added
      amphiphile acts as a supplier of both the vesicular amphiphile and the division
      initiator.

PMID- 15969366
TI  - Oxidation of self-organized nonionic surfactants.
AB  - Nonionic surfactants containing a polyoxyethylene headgroup are known to slowly
      undergo oxidative degradation when exposed to air. The oxidation, which starts by
      abstraction of a hydrogen atom from a methylene group in alpha-position to an
      ether oxygen, is accelerated by metal ions. Silver ion mediated oxidation of a
      technical grade surfactant of this type, Brij 30, was investigated in two types
      of self-assembled systems, a water-in-oil microemulsion and a liquid crystalline
      phase. It was found that in both systems the longer homologues, i.e., the
      surfactant homologues that carry a longer polyoxyethylene chain, decompose faster
      than the shorter homologues. This trend was found to be more pronounced when the
      surfactant is present in a liquid crystal than in a microemulsion. The difference
      is explained in terms of differences in accessibility of the polyoxyethylene
      chains to the silver ions.

PMID- 15969368
TI  - Is there a dipolar interaction of like charges in thin aqueous films?
AB  - The dipole moment and the screened interaction of interfacial charges are
      discussed. We compare this interaction with that of parallel dipoles and show
      that the dipolar picture fails for charges in thin aqueous films.

PMID- 15969369
TI  - Reactivity of acetylenyl-terminated self-assembled monolayers on gold: triazole
      formation.
AB  - We report the reactivity of acetylenyl-terminated self-assembled monolayers
      (SAMs) on gold toward "click" chemistry, Huisgen 1,3-dipolar addition, leading to
      the formation of triazoles. After the formation of acetylenyl-terminated SAMs,
      the triazole formation was performed on the SAMs and the reaction was confirmed
      by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy,
      ellipsometry, and contact angle goniometry. "Click" chemistry has offered a
      versatile strategy for the functionalization in solution chemistry with mild
      reaction conditions and a high compatibility in functional groups, and our result
      shows that the reaction could be applied to acetylenyl-terminated SAMs for the
      introduction of useful functional groups to the surfaces.

PMID- 15969367
TI  - Effect of the flow field on the rheological behavior of aqueous
      cetyltrimethylammonium p-toluenesulfonate solutions.
AB  - It is well-known that solutions of cetyltrimethylammonium p-toluenesulfonate in
      water exhibit a pronounced shear-thickening phenomenon in a specific
      concentration range (0.1-0.8%) when they are subjected to simple-shear flows, as
      a consequence of flow-induced self-assembly of wormlike micelles. This work shows
      that a strong elongational flow field (opposed-jets flow), applied to the same
      solutions, does not lead to extension thickening because the extensional flow
      prevents or destroys micellar association. In flow through a porous medium, a
      substantial increase in apparent viscosity is observed beyond a critical apparent
      shear rate, which surpasses increases observed in simple-shear flows. This is
      explained as the result of a synergistic effect of shear and relatively weak
      elongation on the solution microstructure.

PMID- 15969370
TI  - Swelling behavior of self-assembled monolayers of alkanethiol-terminated
      poly(ethylene glycol): a neutron reflectometry study.
AB  - The swelling behavior of alkanethiol-terminated poly(ethylene glycol) with an
      average molecular weight of 2180 Da (i.e., approximately 45 ethylene glycol, EG,
      units) in contact with water was investigated by neutron reflectometry as a
      function of the morphology of the PEG-SH layer. Amorphous films at a low grafting
      density show significant swelling with an increase of the film thickness from
      approximately 25 A in the dry state to approximately 70 A in contact with D2O,
      which corresponds to a total water uptake of approximately 38 mass %. In
      contrast, quasi-crystalline monolayers exhibit only a small amount of water
      penetrating into the film (approximately 8 mass %) with a corresponding change of
      the layer thickness from approximately 110 to approximately 125 A. The water
      uptake per EG unit corresponds to the literature value of 1.5 for the amorphous
      layer and to only 0.25 in the case of the quasi-crystalline film.

PMID- 15969371
TI  - Partitioning of macrocyclic compounds in a cationic and an anionic micellar
      solution: a small-angle neutron scattering study.
AB  - Following a previous investigation on partitioning of some macrocycle compounds
      in sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium bromide (DTAB)
      aqueous solutions and their effect on the micellar structure, a small-angle
      neutron scattering (SANS) study has been performed at fixed surfactant content
      (0.20 mol/L) and varying macrocycle concentrations from 0.20 up to 1.0 mol/L.
      Conductivity measurements have been also performed in order to evaluate the
      effect of the presence of macrocycles on the critical micellar concentration
      (cmc) of the two surfactants. SANS experimental data were fitted successfully by
      means of a core-plus-shell monodisperse prolate ellipsoid model. It has been
      found that 1,4,7,10,13,16-esaoxacyclooctadecane (18C6) and 4,7,13,16-tetraoxa
      1,10-diazacyclooctadecane (22) do not interact with DTAB micelles whereas their
      sodium complexes interact with SDS aggregates and partially localize, as a
      consequence of electrostatic interaction, on the micellar surface or in the Stern
      layer. 2,5,8,11,14,17-Hexaoxabicyclo[16.4.0] dicosane (B18C6), as a consequence
      of the increased hydrophobic character with respect to 18C6, interacts with DTAB
      hydrocarbon chains and partially localizes in the inner part of micelles. This
      finding has been successfully used to justify the higher amount of B18C6 compared
      to the 18C6 one found in the SDS micellar phase. The substituted crown ether has
      been found localized both on the micelle surface via complex formation and in the
      inner part of micelles as a consequence of the increased hydrophobic character.
      For all systems, the aggregate size primarily decreases with the amount of
      macrocycle in the micellar phase. The interpretation of cmc trends as a function
      ofmacrocycle concentration gives information on its distribution between micellar
      and aqueous phases that is in line with SANS results.

PMID- 15969372
TI  - Streaming potential and electroosmotic flow in heterogeneous circular
      microchannels with nonuniform zeta potentials: requirements of flow rate and
      current continuities.
AB  - Real surfaces are typically heterogeneous, and microchannels with heterogeneous
      surfaces are commonly found due to fabrication defects, material impurities, and
      chemical adsorption from solution. Such surface heterogeneity causes a nonuniform
      surface potential along the microchannel. Other than surface heterogeneity, one
      could also pattern the various surface potentials along the microchannels. To
      understand how such variations affect electrokinetic flow, we proposed a model to
      describe its behavior in circular microchannels with nonuniform surface
      potentials. Unlike other models, we considered the continuities of flow rate and
      electric current simultaneously. These requirements cause a nonuniform electric
      field distribution and pressure gradient along the channel for both pressure
      driven flow (streaming potential) and electric-field-driven flow
      (electroosmosis). The induced nonuniform pressure and electric field influence
      the electrokinetic flow in terms of the velocity profile, the flow rate, and the
      streaming potential.

PMID- 15969373
TI  - Effect of dynamic surfactant adsorption on emulsion stability.
AB  - The effect of dynamic surfactant adsorption on the stability of concentrated oil
      in water emulsions is studied. For this purpose, a modification of the standard
      Brownian dynamics algorithm (Ermak, D.; McCammon, J. A. J. Chem. Phys. 1978, 69,
      1352) previously used to study the behavior of bitumen emulsions assuming
      instantaneous adsorption (Urbina-Villalba, G.; Garcia-Sucre, M. Langmuir 2000,
      16, 7975) was employed. In the present case, dynamic adsorption (DA) was
      accounted for through a time-dependent electrostatic repulsion between the drops,
      a function of the surfactant surface excess. The surface excess was allowed to
      evolve with time according to well-established analytical expressions which
      depend parametrically on the surfactant diffusion constant (Ds) and the total
      surfactant concentration (C). The investigation required appropriate
      incorporation of hydrodynamic interactions in concentrated systems. This was
      achieved through a novel methodology, which expresses the diffusion constant of
      each particle as a function of its local concentration and the shortest distance
      of separation between nearest neighbors. In model systems, the variation of the
      number of drops as a function of time was followed for different magnitudes of
      the apparent diffusion constant D(app) of the surfactant. For each of these
      values, the effect of C and the volume fraction of internal phase (phi) was
      considered. DA was found to influence emulsion stability appreciably at
      moderately high phi. In this case, the average collision time between drops is
      comparable to the time required for the occurrence of a substantial surfactant
      adsorption, but the interdrop separation is sufficiently large to prevent a
      considerable slowdown of particle movement due to hydrodynamic interactions.

PMID- 15969374
TI  - Hybrid polysaccharide-silica nanocomposites prepared by the sol-gel technique.
AB  - New monolithic nanocomposite silica biomaterials were synthesized on the basis of
      various natural polysaccharides and recently introduced completely water-soluble
      precursor tetrakis(2-hydroxyethyl) orthosilicate. The sol-gel processes were
      performed in aqueous solutions without the addition of organic solvents and
      catalysts. The silica polymerization was promoted by the polysaccharides through
      acceleration and catalytic effect on the processes. By introducing poly(vinyl
      alcohol) or poly(ethylene oxide) in the precursor solution, it was shown that the
      jellification took place in the case of the hydroxyl-containing polymer.
      Therefore, it was suggested that the catalysis was caused by a formation of
      hydrogen bonds between hydroxyl groups in macromolecules and products of
      precursor hydrolysis (silanols). It was also demonstrated that the
      polysaccharides radically changed the structure of biomaterials. In place of the
      cross-linked nanoparticles, there was a three-dimensional network from crossed or
      branched fibers and uncrossed spherical particles that filled the mesh space. The
      density of network, thickness of fibers, and properties of synthesized
      biomaterials depended on the polysaccharide type, charged degree of their
      macromolecule, and concentration. By varying these parameters, it was possible to
      manipulate the structural organization of hybrid polysaccharide-silica
      nanocomposites.

PMID- 15969375
TI  - Membrane solubilization by detergent: resistance conferred by thickness.
AB  - The commonly held model for membrane dissolution by detergents/surfactants
      requires lipid transport from the inner to the outer bilayer leaflet ('flip
      flop'). Although applicable to many systems, it fails in cases where cross
      bilayer transport of membrane components is suppressed. In this paper we
      investigate the mechanism for surfactant-induced solubilization of polymeric
      bilayers. To that end, we examine the dissolution of a series of increasingly
      thick, polymer-based vesicles (polymersomes) by a nonionic surfactant, Triton X
      100, using dynamic light scattering. We find that increasing the bilayer
      thickness imparts better resistance to dissolution, so that the concentration
      required for solubilization, after a fixed amount of time, increases nearly
      linearly with membrane thickness. Combining our experimental data with a
      theoretical model, we show that the dominant mechanism for the surfactant-induced
      dissolution of polymeric vesicles, where polymer flip-flop across the membrane is
      suppressed, is the surfactant transport through the bilayer. This mechanism is
      different both qualitatively and quantitatively from the mechanisms by which
      surfactants dissolve pure lipid vesicles.

PMID- 15969376
TI  - Polystyrene-b-poly(acrylic acid) vesicle size control using solution properties
      and hydrophilic block length.
AB  - Polymeric vesicles have attracted considerable attention in recent years, since
      they are a model for biological membranes and have versatile structures with
      several practical applications. In this study, we prepare vesicles from
      polystyrene-b-poly(acrylic acid) block copolymer in dioxane/water and
      dioxane/THF/water mixtures. We then examine the ability of additives (such as
      NaCl, HCl, or NaOH), solvent composition, and hydrophilic block length to control
      vesicle size. Using turbidity measurements and transmission electron microscopy
      (TEM) we show that larger vesicles can be prepared from a given copolymer by
      adding NaCl or HCl, while adding NaOH yields smaller vesicles. The solvent
      composition (ratio of dioxane to THF, as well as the water content) can also
      determine the vesicle size. From a given copolymer, smaller vesicles can be
      prepared by increasing the THF content in the THF/dioxane solvent mixture. In a
      given solvent mixture, vesicle size increases with water content, but such an
      increase is most pronounced when dioxane is used as the solvent. In THF-rich
      solutions, on the other hand, vesicle size changes only slightly with the water
      concentration. As to the effect of the acrylic acid block length, the results
      show that block copolymers with shorter hydrophilic blocks assemble into larger
      vesicles. The effect of additives and solvent composition on vesicle size is
      related to their influence on chain repulsion and aggregation number, whereas the
      effect of acrylic acid block length occurs because of the relationship among the
      block length, the width of the molecular weight distribution, and the
      stabilization of the vesicle curvature.

PMID- 15969377
TI  - In situ shear investigation of the Synperonic A7-water system by small-angle X
      ray scattering and freeze fracture.
AB  - A shear cell was constructed in two variants for simultaneous small-angle X-ray
      scattering and freeze fracture. Using this cell, the changes in the layer
      structure and the domain formation of the Synperonic A7-water system were
      investigated under shear. The reconstructions of both the layer and domain
      structures were not observed in the steady state after 1 h (following a 2 h long
      shear period). Destruction of the lamellar arrangement and formation of
      aggregates occurred during the stress. It was concluded that the tixotropic
      behavior originates rather from the change of the domain structure with a typical
      size range of microm than from the changes of the inner structure of domains with
      lamellar arrangement.

PMID- 15969378
TI  - Temperature quenched DODAB dispersions: fluid and solid state coexistence and
      complex formation with oppositely charged surfactant.
AB  - Dilute dispersions of the synthetic bilayer forming double-chained cationic lipid
      dioctadecyldimethylammonium bromide (DODAB) were investigated. In dispersions
      sonicated above the chain melting temperature Tm (approximately 45 degrees C) it
      was found by H NMR that about 50% of the surfactant chains remained fluid when
      the samples were cooled to room temperature, which is 20 degrees C below Tm. In
      contrast, there was no sign of a fluid fraction in unsonicated samples at room
      temperature. The addition of the anionic surfactant sodium dodecyl sulfate (SDS)
      to DODAB dispersions at room temperature resulted in the formation of an
      essentially stoichiometric DODA-DS complex with frozen chains, as seen by
      titration calorimetry and H NMR experiments. For sonicated samples, turbidity
      experiments demonstrated that, after a fast complexation reaction, the system
      remains colloidally stable unless the SDS-to-DODAB mixing ratio is too close to
      unity. H NMR experiments also showed that in the unreacted DODAB the fraction of
      fluid chains remained close to 50%, indicating either that SDS reacts equally
      fast with fluid and frozen DODAB or that there is a relaxation of the fluid
      fraction after the complexation. The melting enthalpy and the melting temperature
      of the alkyl chains rise gradually as the mixing ratio increases. We observed
      with cryo-TEM that the fraction of large unilamellar vesicles was significantly
      larger after addition of SDS. This indicates vesicle fusion. Based on both wide-
      and small-angle X-ray scattering patterns, the structure of the equimolar SDS
      DODAB complex at 25 degress C was proposed to be lamellar.

PMID- 15969380
TI  - Cosurfactant effect of a semifluorinated alkane at a fluorocarbon/water
      interface: impact on the stabilization of fluorocarbon-in-water emulsions.
AB  - Previous work has demonstrated that semifluorinated alkanes CnF2n+1CmH2m+1 (FnHm
      diblocks), when used in conjunction with phospholipids, strongly stabilize
      fluorocarbon (FC)-in-water emulsions destined to be used as oxygen carriers.
      Although the presence of FnHm diblocks in the emulsion's interfacial phospholipid
      film was suggested to account for the observed stabilization, no direct proof of
      the diblock's location has been provided so far. We now report definite
      experimental evidence of the diblock's presence at the interfacial film, both on
      a macroscopic level by investigating the FC/water interface using the pendant
      drop method and directly on emulsions by monitoring their stability for various
      phospholipid chain lengths. We first establish that F8H16 has a strong
      cosurfactant effect with phospholipids [dimyristoylphosphatidylcholine (DMPC),
      dilaurylphosphatidylcholine (DLPC), dioctanoylphosphatidylcholine (PCL8)] at a
      perfluorooctyl bromide (PFOB)/water interface, as evidenced by a dramatic F8H16
      concentration-dependent decrease of the interfacial tension. Where FC emulsions
      are concerned, we show that the stabilization effect, which consists of a
      decrease of the rate of molecular diffusion of the FC, depends strongly on the
      length of the phospholipid's fatty chain as compared to the length of the
      hydrocarbon segment, Hm, of the diblock. Stabilization is maximized when the Hm
      length is similar to that of the phospholipid's fatty chains. A strong mismatch
      between Hm and the phospholipid chain length can actually destabilize the
      emulsion. A different destabilization mechanism is then at work: coalescence. The
      presence of F8H16 at the interfacial film is further supported by the fact that
      perfluorodecyl bromide, a heavy analogue of PFOB that stabilizes PFOB emulsions
      by lowering the solubility and diffusibility of the emulsion's dispersed FC
      phase, exercises its stabilizing effect similarly for all the phospholipids
      investigated.

PMID- 15969379
TI  - Effect of surfactant type on surfactant-maltodextrin interactions: isothermal
      titration calorimetry, surface tensiometry, and ultrasonic velocimetry study.
AB  - Isothermal titration calorimetry (ITC), surface tensiometry, and ultrasonic
      velocimetry were used to characterize surfactant-maltodextrin interactions in
      buffer solutions (pH 7.0, 10 mM NaCl, 20 mM Trizma base, 30.0 degrees C).
      Experiments were carried out using three surfactants with similar nonpolar tail
      groups (C12) but different charged headgroups: anionic (sodium dodecyl sulfate,
      SDS), cationic (dodecyl trimethylammonium bromide, DTAB), and nonionic
      (polyoxyethylene 23 lauryl ether, Brij35). All three surfactants bound to
      maltodextrin, with the binding characteristics depending on whether the
      surfactant headgroup was ionic or nonionic. The amounts of surfactant bound to
      0.5% w/v maltodextrin (DE 5) at saturation were < 0.3 mM Brij35, approximately 1
      1.6 mM SDS, and approximately 1.5 mM DTAB. ITC measurements indicated that
      surfactant binding to maltodextrin was exothermic. Surface tension measurements
      indicated that the DTAB-maltodextrin complex was more surface active than DTAB
      alone but that SDS- and Brij35- maltodextrin complexes were less surface active
      than the surfactants alone.

PMID- 15969381
TI  - On the structure of poly(N-isopropylacrylamide) microgel particles.
AB  - This investigation presents a study of the internal structure of poly(NIPAM/xBA)
      microgel particles (NIPAM and BA are N-isopropylacrylamide and N,N'-methylene
      bisacrylamide, respectively). In this study, x is the wt % of BA used during
      microgel synthesis. Two values of x were used to prepare the microgels, 1 and 10.
      The microgel dispersions were investigated using photon correlation spectroscopy
      (PCS) and small-angle neutron scattering (SANS). These measurements were made as
      a function of temperature in the range 30-50 degrees C. Scattering maxima were
      observed for the microgels when the dispersion temperatures were less than their
      volume phase transition temperatures. The SANS data were fitted using a model
      which consisted of Porod and Ornstein-Zernike form factors. The analysis showed
      that the macroscopic hydrodynamic diameter of the microgel particles and the
      submicroscopic mesh size of the network are linearly related. This is the first
      study to demonstrate affine swelling for poly(NIPAM/xBA) microgels. Furthermore,
      the mesh size does not appear to be strongly affected by x. The data suggest that
      the swollen particles have a mostly homogeneous structure, although evidence for
      a thin, low segment density shell is presented. The study confirms that
      poly(NIPAM/xBA) microgel particles have a core-shell structure. The shell has an
      average thickness of approximately 20 nm for poly(NIPAM/1BA) particles which
      appears to be independent of temperature over the range studied. The analysis
      suggests that the particles contained approximately 50 vol % water at 50 degrees
      C. The molar mass of the poly(NIPAM/1BA) microgel particles was estimated as 6 x
      10(9) g mol(-1).

PMID- 15969382
TI  - Mixed micelles of fluorocarbon and hydrocarbon surfactants. A small angle neutron
      scattering study.
AB  - Mixtures of the partly fluorinated cationic surfactant HFDePC (N-(1, 1,2,2
      tetrahydroperfluorodecanyl)-pyridinium chloride and deuterated headgroup) with
      C16TAC, hexadecyl-trimethylammonium chloride, have been investigated using small
      angle neutron scattering with contrast matching. Earlier results from this system
      suggested that a demixing occurred, into two coexisting populations of micelles,
      hydrocarbon-rich and fluorocarbon-rich, respectively. The present results could
      be explained by one type of mixed micelles with an inhomogeneous distribution of
      fluorinated and hydrogenated surfactants within the micelles although a demixing
      cannot be definitely excluded.

PMID- 15969383
TI  - Directed assembly and rupture mechanics of colloidal aggregates.
AB  - The macroscopic rheological behavior of colloidal gels arises from the
      micromechanical properties of the gel backbone, which are governed by nanoscale
      particle interactions. These colloidal interactions have been commonly understood
      in terms of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Recent work has
      shown, however, that nonidealities, such as surface roughness and charge
      nonuniformity, may cause the particle interactions to significantly deviate from
      DLVO predictions at near-contact separations. Here we present novel techniques
      for directing the assembly of colloidal aggregates that mimic the gel backbone,
      based on optical micromanipulation of multiple particles using laser tweezers.
      This also provides an in situ method for measuring near-contact interactions via
      single-bond rupture forces. We find that PMMA particles aggregated in the
      presence of nonorganic salts exhibit interparticle bond strengths more than 10
      times greater than those predicted by DLVO theory. However, good agreement is
      found with DLVO predictions when the anionic surfactant sodium dodecyl sulfate
      (SDS) is used as the flocculant.

PMID- 15969384
TI  - Shear-induced morphology transition and microphase separation in a lamellar phase
      doped with clay particles.
AB  - We report on the influence of shear on a nonionic lamellar phase of
      tetraethyleneglycol monododecyl ether (C12E4) in D2O containing clay particles
      (Laponite RD). The system was studied by means of small-angle light scattering
      (SALS) and small-angle neutron scattering (SANS) under shear. The SANS
      experiments were conducted using a H2O/D2O mixture of the respective scattering
      length density to selectively match the clay scattering. The rheological
      properties show the familiar shear thickening regime associated with the
      formation of multilamellar vesicles (MLVs) and a shear thinning regime at higher
      stresses. The variation of viscosity is less pronounced as commonly observed. In
      the shear thinning regime, depolarized SALS reveals an unexpectedly strong
      variation of the MLV size. SANS experiments using the samples with lamellar
      contrast reveal a change in interlamellar spacing of up to 30% at stresses that
      lead to MLV formation. This change is much more pronounced than the change
      observed, when shear suppresses thermal bilayer undulations. Microphase
      separation occurs, and as a consequence, the lamellar spacing decreases
      drastically. The coincidence of the change in lamellar spacing and the onset of
      MLV formation is a strong indication for a morphology-driven microphase
      separation.

PMID- 15969385
TI  - Fluorescence study of aggregation in water of PEO-grafted polydiphenylamine.
AB  - Fluorescence spectra of water-soluble conducting poly(ethylene oxide)-grafted
      polydiphenylamines (PDPA-g-PEOs with the M(n)s of PEO 350, 750, and 2000) in
      water were determined and interpreted. The emissions of the PDPA-g-PEOs occurred
      in the range from 360 to 700 nm and were dependent on their concentrations, PEO
      chain length, extent of oxidation, pH, and temperature. An optimum concentration,
      above which the fluorescence intensity decreased dramatically because of
      quenching, was observed. This quenching was a result of the aggregation of PDPA-g
      PEO macromolecules in water. The doped PDPA-g-PEO molecules provided a lower
      optimum concentration than the corresponding reduced-state macromolecules. A rod
      shaped microstructure of nanoscale size was generated through the aggregation of
      the PDPA-g-PEO macromolecules. This microstructure was also confirmed by dynamic
      light scattering, atomic force microscopy, and surface elemental analysis.

PMID- 15969386
TI  - Factors influencing the size of PEO complexes with a tyrosine-rich polypeptide.
AB  - Aqueous complexes of PEY1, a 36 100 Da random synthetic peptide of tyrosine (50
      mol %) and glutamic acid (50 mol %), with poly(ethylene oxide) (PEO) were studied
      as functions of PEO molecular weight, mixing ratio of PEO and PEY1, and the
      presence of calcium ions. Without calcium ions, the complexes were water soluble,
      with each complex consisting of a single PEO chain with many bound PEY1 chains.
      In the presence of 1 mM calcium ions, PEY1 formed colloidal aggregates with
      intermediate molecular weight PEO (10(5) to 10(6) Da). By contrast, very high
      molecular weight PEO (8 x 10(6) Da) with calcium ions formed large hydrogels when
      mixed with PEY1. It is proposed that PEY1 molecules completely bind to low
      molecular PEO and thus are deactivated from causing the coupling of multiple PEO
      chains, whereas deactivation of PEY1 on very high molecular weight PEO clusters
      is a slower process, giving an opportunity for cluster-cluster aggregation.

PMID- 15969387
TI  - Universal occurrence of soot superaggregates with a fractal dimension of 2.6 in
      heavily sooting laminar diffusion flames.
AB  - Using small-angle light scattering we show that a new phase of soot with size ca.
      10 microm and a fractal dimension of D approximately equal to 2.6 exists in
      laminar diffusion flames for a wide range of heavily sooting fuels. This new
      phase appears to be a supramicrometer extension of the well-known submicrometer,
      D approximately equal to 1.8 phase of soot formed via diffusion-limited cluster
      aggregation (DLCA). The occurrence of this new soot phase correlates with an
      empirical sooting index for fuels. This supports a creation scenario in which
      these supramicrometer aggregates are created via a percolation of the
      submicrometer, D approximately equal to 1.8 aggregates.

PMID- 15969389
TI  - A computer modeling study of the competitive adsorption of water and organic
      surfactants at surfaces of the mineral scheelite.
AB  - Atomistic computer simulation techniques were employed to investigate the
      interaction of a selection of organic surfactant molecules with a range of
      scheelite surfaces. The adsorbates coordinate mainly to the surfaces through
      interaction between their oxygen (or nitrogen) atoms to surface calcium ions,
      followed by hydrogen-bonded interactions to surface oxygen ions. Bridging between
      two surface calcium ions is the preferred mode of adsorption, but a bidentate
      interaction by two adsorbate oxygen ions to the same surface calcium ion is also
      a stable configuration and multiple interactions between surfaces and adsorbate
      molecules lead to the largest adsorption energies. All adsorbates containing
      carbonyl and hydroxy groups interact strongly with the surfaces, releasing
      energies between approximately 80 and 170 kJ mol(-1), but methylamine containing
      only the -NH2 functional group adsorbs to the surfaces to a much lesser extent
      (55-86 kJ mol(-1)). Both hydroxymethanamide and hydroxyethanal adsorb to some
      surfaces in an eclipsed conformation, which is a requisite for these functional
      groups. Sorption of the organic material by replacement of preadsorbed water at
      different surface features is calculated to be mainly exothermic for methanoic
      acid, but less so for the hydroxymethanamide and hydroxyethanal molecules,
      whereas methylamine would not replace preadsorbed water at the scheelite
      surfaces. The efficacy of the surfactant molecules is hence calculated to be
      carboxylic acids > alkyl hydroxamates > hydroxyaldehydes > alkylamines. The
      results from this study suggest that computer simulations may provide a route to
      the identification or even design of particular organic surfactants for use in
      mineral separation processes.

PMID- 15969388
TI  - Self-organization of self-assembled tetrameric porphyrin arrays on surfaces.
AB  - The incorporation of designed self-assembled supramolecular structures into
      devices requires deposition onto surfaces with retention of both structure and
      function. This remains a challenge and can present a significant barrier to
      developing devices using self-organizing materials. To examine the role of
      peripheral groups in the self-organization of self-assembled multiporphyrinic
      arrays on surfaces, Pd(II)-linked square and Pt(II)-linked trapezoidal tetrameric
      porphyrin arrays with peripheral tert-butylphenyl or dodecyloxyphenyl
      functionalities were investigated using various spectroscopies and atomic force
      microscopy. The Pd(II) assembled squares disassemble upon deposition on glass
      surfaces, while the Pt(II) assembled trapezoids are more robust and can be
      routinely cast on these surfaces. The orientation and length of the peripheral
      alkyl substituents influence the resultant structures on surfaces. The tert
      butylphenyl-substituted porphyrin array forms discrete columnar stacks, which
      assemble in a vertical direction via pi-stacking interactions among the
      macrocycles. The tetrameric porphyrin array with dodecyloxyphenyl groups forms a
      continuous film via van der Waals interactions among the peripheral hydrocarbon
      chains. The super-molecules with liquid crystal-forming moieties also form three
      dimensional crystalline structures at higher deposition concentrations. These
      observations clearly demonstrate that the number, position, and nature of the
      peripheral groups and the supramolecular structure and dynamics, as well as the
      energetics of interactions with the surface, are of key importance to the two
      dimensional and three-dimensional self-organization of assemblies such as
      porphyrin arrays on surfaces.

PMID- 15969390
TI  - Molecular-level approach to inhibit degradations of alkanethiol self-assembled
      monolayers in aqueous media.
AB  - A molecular-level approach is developed to prevent or inhibit the degradation
      processes of alkanethiol self-assembled monolayers (SAMs). Previous studies
      revealed two degradation pathways: direct desorption and oxidation-desorption. By
      use of scanning tunneling microscopy (STM) and atomic force microscopy (AFM), in
      situ and time-dependent imaging reveals and confirms that degradations of
      alkanethiol SAMs on gold mainly initiate at defect sites, such as domain
      boundaries and vacancy islands, and then propagate into the ordered domains. Our
      approach targets at attaching small molecules with preferred adhesion to the
      defects. The best candidates are aqueous media containing a small amount of
      amphiphilic surfactant molecules, such as N,N-dimethylformamide (DMF) or dimethyl
      sulfoxide (DMSO). High-resolution studies demonstrate that DMSO and DMF molecules
      attach to SAM surfaces and more favorably at defect sites, forming relatively
      stable adsorbates. This attachment increases the activation energy sufficiently
      to inhibit both degradation pathways. The robustness of this approach has been
      investigated as a function of surfactant concentration, solution temperature, and
      the stirring condition. Molecular-level mechanisms and energetics for degradation
      inhibition of SAMs are also discussed in detail.

PMID- 15969391
TI  - Dynamic adsorption and surface tension of aqueous dilauroylphosphatidylcholine
      dispersions under physiological conditions.
AB  - The dynamic surface tension and equilibrium adsorption behavior of DLPC
      dispersions in phosphate buffer saline at 37 and 25 degrees C was studied with
      tensiometry, infrared reflection--absorption spectroscopy (IRRAS), and
      ellipsometry. The results are compared with those in water (Pinazo et al.
      Langmuir 2002, 18, 8888). Even though the pH and salinity have no apparent effect
      on the equilibrium surface tension and the surface pressure--area isotherm, they
      affect the dynamic surface tension by decreasing the adsorption rate and
      increasing the dynamic tension minima at a pulsating area of 20 or 80 cycles per
      minute. Moreover, IRRAS and ellipsometry results show that the adsorbed layers
      and the spread monolayers have larger area per molecule, or looser packing, in
      buffer than in water. A new hypothesis is proposed to elucidate the effect of
      pH/salinity on this zwitterionic surfactant: there is some specific interaction
      or binding between the ions from the buffer saline with the polar headgroups of
      DLPC. This interaction induces stronger intermolecular repulsions of the
      surfactant layer in buffer than that in water, despite the expected electrostatic
      screening effect, and causes higher dynamic surface tensions. The results have
      implications in designing lung surfactant replacement formulations.

PMID- 15969392
TI  - Effect of layer integrity of spin self-assembled multilayer films on surface
      wettability.
AB  - We investigated the correlation between surface wettability and internal
      structure of polyelectrolyte (PE)/PE and PE/inorganic multilayer films prepared
      by the spin self-assembly (SA) method. Spin self-assembled poly(allylamine
      hydrochloride) (PAH)/poly(sodium 4-styrenesulfonate) (PSS) multilayer films
      deposited from PE solutions of 10 mM show the distinct oscillation in contact
      angles with variation of the outermost PE layer, representing the saturated
      values in contact angles of individual PAH and PSS layers. These contact angles
      are also well consistent with the angles measured from respective PE layers
      (i.e., PAH and PSS) of the spin SA (PAH/CdS-COO-) and (CdS-NH3+/PSS) films
      carrying the flat interface between PE and inorganic CdS nanoparticle layers as
      confirmed by X-ray reflectivity. Furthermore, based on the contact angle of CdS
      NH3+ layer in the ordered (CdS-NH3+/PSS) films, the change in surface wettability
      of CdS-NH3+ layers of two different spin SA (CdS-NH3+/poly(methacrylic acid)
      (PMAA)) multilayer films with ordered and disordered internal structure is also
      investigated. The films with ordered and disordered internal structure were
      fabricated by the pH adjustment of PMAA. The CdS-NH3+ layer in both CdS-NH3+/PSS
      and CdS-NH3+/PMAA multilayer films with the ordered internal structure has the
      contact angle of about 25 +/- 2 degrees irrespective of the PSS or PMAA sublayer.
      As a result, the same surface wettability of PE or inorganic layers, despite
      different sublayers, strongly indicates that the spin SA method in optimum
      condition allows the top surface to be completely covered with a low level
      ofinterdigitation with a sublayer at each deposition step, and this leads to the
      conclusion that physical and chemical characteristics of the sublayers have no
      significant influence on those of the outermost layer.

PMID- 15969393
TI  - Contact angles and their hysteresis as a measure of liquid-solid adhesion.
AB  - The wetting behavior of a series of aliphatic polyamides was examined. Polyamides
      and polyethylene were molded against glass to produce smooth surfaces. 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
      contact angle hysteresis increased. Wetting free energies calculated from contact
      angles were equal to those from dewetting, suggesting that contact angle
      hysteresis did not arise from surface anomalies, but from hydrogen bonding
      between water and the amide groups in the polyamide surfaces.

PMID- 15969394
TI  - Interfacial rheology of petroleum asphaltenes at the oil-water interface.
AB  - A biconical bob interfacial shear rheometer was used to study the mechanical
      properties of asphaltenic films adsorbed at the oil-water interface. Solutions of
      asphaltenes isolated from four crude oils were dissolved in a model oil of
      heptane and toluene and allowed to adsorb and age in contact with water. Film
      elasticity (G') values were measured over a period of several days, and yield
      stresses and film masses were determined at the end of testing. The degree of
      film consolidation was determined from ratios of G'/film mass and yield
      stress/G'. Asphaltenes with higher concentrations of heavy metals (Ni, 330-360
      ppm; V, 950-1000 ppm), lower aromaticity (H/C, 1.24-1.29), and higher polarity
      (N, 1.87-1.99) formed films of high elasticity, yield stress, and consolidation.
      Rapid adsorption kinetics and G' increases were seen when asphaltenes were near
      their solubility limit in heptane-toluene mixtures (approximately 50% (v/v)
      toluene). In solvents of greater aromaticity, adsorption kinetics and film masses
      were reduced at comparable aging times. Poor film forming asphaltenes had yield
      stress/G' values ((1.01-1.21) x 10(-2)) more than 4-fold lower than those of good
      film forming asphaltenes. n-heptane asphaltenes fractionated by filtering
      solutions prepared at low aromaticity (approximately 40% toluene in mixtures of
      heptane and toluene) possessed higher concentrations of heavy metals and nitrogen
      and higher aromaticity. The less soluble fractions of good film forming
      asphaltenes exhibited enhanced adsorption kinetics and higher G' and yield stress
      values in pure toluene. Replacing the asphaltene solutions with neat heptane
      toluene highlighted the ability of films to consolidate and become more elastic
      over several hours. Adding resins in solution to a partially consolidated film
      caused a rapid reduction in elasticity followed by gradual but modest
      consolidation. This study is among the first to directly relate asphaltene
      chemistry to adsorption kinetics, adsorbed film mechanical properties, and
      consolidation kinetics.

PMID- 15969395
TI  - Effect of surface composition on the adsorption of photosystem I onto
      alkanethiolate self-assembled monolayers on gold.
AB  - We have used self-assembled monolayers (SAMs) prepared from omega-terminated
      alkanethiols on gold to generate model surfaces and examine the effect of surface
      composition on the adsorption of Photosystem I (PSI), stabilized in aqueous
      solution by Triton X-100. Triton-stabilized PSI adsorbs to high-energy surfaces
      prepared from HO- and HO2C-terminated alkanethiols but does not adsorb to low
      energy surfaces. The inhibition of PSI adsorption at low-energy surfaces is
      consistent with the presence of a layer of Triton X-100 that adsorbs atop the
      hydrophobic SAM and presents a protein-resistant poly(ethylene glycol) (PEG)
      surface. While the presence of the PEG surface prevents the adsorption of PSI,
      the displacement of the inhibiting layer of Triton X-100 by dodecanol, a more
      active surfactant, greatly enhances the adsorption of PSI. This inhibiting effect
      by Triton X-100 can be extended to other protein systems such as bovine serum
      albumin.

PMID- 15969396
TI  - Structure and reactivity of mixed omega-carboxyalkyl/alkyl monolayers on silicon:
      ATR-FTIR spectroscopy and contact angle titration.
AB  - The structure, reactivity, and acid-base properties of mixed monolayers prepared
      by photochemical reaction of hydrogen-terminated silicon with mixtures of ethyl
      undecylenate and n-alkenes were studied by ATR-FTIR spectroscopy and contact
      angle measurements. The surface composition of the mixed monolayers and its
      correlation with the hydrolysis reactivity of terminal ethoxycarbonyl (ester)
      groups were investigated by systematically varying the mole fraction of ethyl
      undecylenate and the chain length of the unsubstituted alkenes in the binary
      deposition solution. It has been shown that the mole fraction of ester groups on
      the surface deviates only slightly from the mole fraction of ethyl undecylenate
      in the solution. The efficiency of ester hydrolysis under acidic conditions is
      significantly influenced by the monolayer structure, i.e., the surface density of
      ester groups and length of the unsubstituted alkyl chains. In addition, we find
      that mixed omega-alkanoic acid/alkyl monolayers on silicon (prepared via
      hydrolysis) exhibit well-defined contact angle titration curves from which the
      surface acid dissociation constants were determined. The results were compared
      with the acid-base properties reported in the literature for carboxylic acid
      terminated alkylsiloxane monolayers on hydroxylated silicon and for omega
      mercaptoalkanoic acid/alkanethiolate monolayers on gold. The weak pKa dependence
      (deltapKa approximately 1) on the surface density of carboxylic acid groups and
      on the length of unsubstituted alkyl chains is attributed to variations of the
      microenvironment of the acid moieties. These experimental findings provide
      fundamental knowledge at the molecular level for the preparation of bioreactive
      surfaces of controlled reactivity on crystalline semiconductor substrates.

PMID- 15969397
TI  - Adsorption of alkyl polyglucosides on the solid/water interface: equilibrium
      effects of alkyl chain length and head group polymerization.
AB  - The equilibrium adsorption behavior of two n-alkyl-beta-D-glucosides (octyl
      (C8G1) and decyl (C10G1)) and four n-alkyl-beta-D-maltosides (octyl (C8G2), decyl
      (C10G2), dodecyl (C12G2), and tetradecyl (C14G2)) from aqueous solution on a
      titania surface, as measured by ellipsometry, has been investigated. The main
      focus has been on the effect of changes in the alkyl chain length and headgroup
      polymerization, but a comparison with their adsorption on the silica/water and
      air/water interfaces is also presented. Some comparison with the corresponding
      adsorption of ethylene oxide surfactants, in particular C10E6 and C12E6, is given
      as well. For all alkyl polyglucosides, the maximum adsorbed amount on titania is
      reached slightly below the critical micelle concentration (cmc), where it levels
      off to a plateau and the amount adsorbed corresponds roughly to a bilayer.
      However, there is no evidence that this is the actual conformation of the
      surfactant assemblies on the surface, but the surfactants could also be arranged
      in a micellar network. On hydrophilic silica, the adsorbed amount is a magnitude
      lower than on titania, corresponding roughly to a layer of surfactants lying flat
      on the surface. A change in the alkyl chain length does not result in any change
      in the plateau molar adsorbed amount at equilibrium; however, the isotherm slope
      for the alkyl maltosides increases with increasing chain length. Headgroup
      polymerization on the other hand affects the adsorbed amount. The alkyl
      glucosides start adsorbing at lower bulk concentrations than the maltosides and
      equilibrate at higher adsorbed amounts above the cmc. When compared with the
      ethylene oxide (EO) surfactants, it is confirmed that the EO surfactants hardly
      adsorb on titania, since the measured changes in the ellipsometric angles are
      within the noise level. They do, however, adsorb strongly on silica.

PMID- 15969398
TI  - Sequential collapse transitions in a Langmuir monolayer.
AB  - Unusual sequential collapse transitions are investigated in a lignoceric acid
      Langmuir monolayer. The nucleation of monolayer collapse is first initiated in
      the solid, S, phase but at remarkably low surface pressure where small three
      dimensional (3D) granular dots appear. The density of nucleation centers
      increases, and the 3D dots prevail over the monolayer (surface roughening regime)
      as the surface pressure increases, but individual dots neither grow very much in
      size nor evolve into other shapes such as stripes or elongated dots. On further
      compression the second collapse mode manifests itself by highly anisotropic,
      global crack arrays (anisotropic cracking regime) where the surface pressure
      "kink" appears in the isotherm. In the latter regime, various forms of 3D curved
      filaments develop in the crack regions, and they break into smaller fragments
      with a typical relaxation time (approximately 60 ms).

PMID- 15969399
TI  - Mixed polymer brushes by sequential polymer addition: anchoring layer effect.
AB  - Smart surfaces can be described as surfaces that have the ability to respond in a
      controllable fashion to specific environmental stimuli. A heterogeneous (mixed)
      polymer brush (HPB) can provide a synthetic route to designing smart polymer
      surfaces. In this research we study HPB comprised of end-grafted polystyrene (PS)
      and poly(2-vinyl pyridine) (P2VP). The synthesis of the HPB involves the use of
      an "intermolecular glue" acting as a binding/anchoring interlayer between the
      polymer brush and the substrate, a silicon wafer. We compare anchoring layers of
      epoxysilane (GPS), which forms a self-assembled monolayer with epoxy
      functionality, to poly(glycidyl methacrylate) (PGMA), which forms a
      macromolecular monolayer with epoxy functionality. The PS and P2VP were deposited
      onto the wafers in a sequential fashion to chemically graft PS in a first step
      and subsequently graft P2VP. Rinsing the HPB in selective solvents and observing
      the change in water contact angle as a function of the HPB composition studied
      the switching nature of the HPB. Scanning probe microscopy was used to probe the
      topography and phase imagery of the HPB. The nature of the anchoring layer
      significantly affected the wettability and morphology of the mixed brushes.

PMID- 15969400
TI  - Effect of the interfacial chemical environment on in-plane electronic conduction
      of indium tin oxide: role of surface charge, dipole magnitude, and carrier
      injection.
AB  - Reaction of the indium tin oxide (ITO) surface with Bronsted acids (bases) leads
      to increases (decreases) in its in-plane conductance as measured by a four-point
      probe configuration. The conductance varies monotonically with pH, suggesting
      that the degree of surface protonation or hydroxylation controls the surface
      charge density, which in turn affects the width of the n-type depletion layer and
      ultimately the in-plane conductance. Measurements at constant pH with a series of
      tetraalkylammonium hydroxide species of varying cation size indicate that surface
      dipoles also affect ITO conductance by modulating the magnitude of the surface
      polarization. Modulating the double layer with varying aqueous salt solutions
      also affects ITO conductance, though not to the same degree as strong Bronsted
      acids and bases. Solvents of varying dielectric constant and proton donating
      ability (ethanol, dimethylformamide) decrease ITO conductance relative to H2O. In
      addition, changing solvent gives rise to thermally derived conductance
      transients, which result from exothermic solvent mixing. The self-assembly of
      alkanethiols at the surface increases the conductance of ITO films, most likely
      through carrier population effects. In all cases examined the combined effects of
      surface charge, adsorbed dipole layer magnitude, and carrier injection are
      responsible for altering the ITO conductance. Besides being directly applicable
      to the control of electronic properties, these results also point to the use of
      four-point probe resistance measurements in condensed phase sensing applications.

PMID- 15969401
TI  - Ratcheting motion of liquid drops on gradient surfaces.
AB  - The motions of liquid drops of various surface tensions and viscosities were
      investigated on a solid substrate possessing a gradient of wettability. A drop of
      any size moves spontaneously on such a surface when the contact angle hysteresis
      is negligible; but it has to be larger than a critical size in order to move on a
      hysteretic surface. The hysteresis can, however, be reduced or eliminated with
      vibration that allows the drop to sample various metastable states, thereby
      setting it to the path of global energy minima. Significant amplification of
      velocity is observed with the frequency of forcing vibration matching the natural
      harmonics of drop oscillation. It is suggested that the main cause for velocity
      amplification is related to resonant shape fluctuation, which can be illustrated
      by periodically deforming and relaxing the drop at low frequencies.

PMID- 15969402
TI  - An in situ FTIR-ATR study of polyacrylate adsorbed onto hematite at high pH and
      high ionic strength.
AB  - FTIR-ATR was used to examine in situ the interaction of polyacrylate and hematite
      at pH 13. Static light scattering and mobility measurements were used to assess
      solution polyacrylate dimensions and hematite surface charge, respectively.
      Polyacrylate adsorption occurred only with the addition of electrolyte (e.g.,
      NaCl), and it was found that excess cations, up to approximately 1 M, facilitated
      adsorption, above which the effect was found to plateau. At pH 13 and at low
      ionic strength, adsorption of polyacrylate onto hematite is facilitated by
      cations in solution shielding both the negative acrylate functionality of the
      polymer and the negative hematite surface. The shielding of the hematite surface
      continues to increase with increasing salt concentration up to a measured 3 M.
      Similarly, the shielding of the polymer increased with electrolyte concentration
      up to approximately 1 M salt, beyond which no further increase in shielding was
      observed. At this concentration the polymer assumes a finite minimum size in
      solution that ultimately limits the amount adsorbed. The dimension of the polymer
      in solution was found to be independent of monovalent cation type. Thus, at high
      pH and high ionic strength adsorption is determined by the degree of hematite
      surface charge reduction. The cation-hematite surface interaction was found to be
      specific, with lithium leading to greater polyacrylate adsorption than sodium,
      which was followed by cesium. The stronger affinity of lithium for the hematite
      surface over sodium and cesium is indicative of the inverse lyotropic adsorption
      series and has been rationalized in the past by the "structure-making-structure
      breaking" model. These results provide a useful insight into the likely
      adsorption mechanism for polyacrylate flocculants at high pH and ionic strength
      onto residues in the Bayer processing of bauxite.

PMID- 15969403
TI  - Zeta potential orientation dependence of sapphire substrates.
AB  - The zeta potential of planar sapphire substrates for three different
      crystallographic orientations was measured by a streaming potential technique in
      the presence of KCl and (CH3)4NCl electrolytes. The streaming potential was
      measured for large single crystalline C-plane (0001), A-plane (1120), and R-plane
      (1102) wafers over a full pH range at three or more ionic strengths ranging from
      1 to 100 mM. The roughness of the epi-polished wafers was verified using atomic
      force microscopy to be on the order of atomic scale, and X-ray photoelectron
      spectroscopy (XPS) was used to ensure that the samples were free of silica and
      other contaminants. The results reveal a shift in the isoelectric point (iep) of
      the three samples by as much as two pH units, with the R-plane surface exhibiting
      the most acidic behavior and the C-plane samples having the highest iep. The iep
      at all ionic strengths was tightly centered around a single pH for each wafer.
      These values of iep are substantially different from the range of pH 8-10
      consistently reported in the literature for alpha-Al2O3 particles. Particle zeta
      potential measurements were performed on a model powder using phase analysis
      light scattering, and the iep was confirmed to occur at pH 8. Modified Auger
      parameters (MAP) were calculated from XPS spectra of a monolayer of iridium metal
      deposited on the sapphire by electron beam deposition. A shift in MAP consistent
      with the observed differences in iep of the surfaces confirms the effect of
      surface structure on the transfer of charge between the Ir and sapphire, hence
      accounting for the changes in acidity as a function of crystallographic
      orientation.

PMID- 15969404
TI  - Chemical force microscopy of mixed self-assembled monolayers of alkanethiols on
      gold: evidence for phase separation.
AB  - Mixed self-assembled monolayers formed by the coadsorption of hydroxyl- and
      methyl-terminated alkanethiols with similar chain lengths have been characterized
      by friction force microscopy. Friction coefficients have been determined by
      assuming a fit to Amonton's law. The friction coefficients vary linearly with the
      fraction of polar-terminated adsorbates in the self-assembled monolayer (SAM).
      With carboxylic acid-terminated tips, the coefficient of friction increases with
      the fraction of hydroxyl-terminated thiols, while with methyl-terminated tips it
      decreases. Similar trends are observed for pull-off forces, which increase and
      decrease as a function of the fraction of polar-terminated adsorbates for
      carboxylic acid- and methyl-terminated adsorbates, respectively. Analysis of
      histograms of adhesion forces has yielded insights into the phase structure of
      mixed SAMs. Single-component monolayers yield histograms that may be fitted to
      symmetric Gaussian distributions, irrespective of the nature of the terminal
      group on either the tip or the SAM. However, mixed monolayers yield broad,
      asymmetric distributions that could not be fitted with a Gaussian distribution.
      The best explanation for these data is that mixed SAMs of hydroxyl- and methyl
      terminated alkanethiols of similar chain length form phase-separated structures.

PMID- 15969405
TI  - Ultrathin films of semiconducting polymers on water.
AB  - Ultrathin films of polythiophene derivatives spread on water were studied by
      means of synchrotron radiation, using grazing incidence diffraction and
      (specular) reflectometry to obtain the molecular orientation in the films. The
      semicrystalline films were anisotropic, showing a strong tendency of orienting
      the crystalline alpha-axis perpendicularly to the water subphase. The crystalline
      domains extend essentially through the entire sample thickness, found to be 10-15
      nm. A large expansion of the unit cell alpha-parameter was seen upon doping the
      films in situ. The reflectometry data were well-fitted by a model with a
      sinusoidal density variation being damped toward the water subphase. This
      indicates that the crystalline order was most developed at the polymer-air
      interface and deteriorated down toward the water, possibly due to the
      hydrophobicity of the alkyl side chains.

PMID- 15969406
TI  - Alternative method for fabricating chemically functionalized AFM tips: silane
      modification of HF-treated Si3N4 probes.
AB  - An alternative method for fabricating functionalized, atomic force microscopy
      (AFM) tips is presented. This technique is simple and requires only minimal
      preparation and tip modification to generate chemically sensitive probes that
      have a robust organic monolayer of flexible terminal chemistry attached to the
      surface. Specifically, commercially microfabricated Si3N4 AFM tips were modified
      with self-assembled monolayers (SAMs) of octadecyltrichlorosilane and (11
      bromoundecyl)trichlorosilane after removing the native silicon oxide surface
      layer with concentrated hydrofluoric acid. The structure of these SAM films on
      solid silicon nitride surfaces was studied using contact angle goniometry and
      Fourier transform infrared spectroscopy. Pull-off force measurements on various
      bare (mica, graphite, and silicon) and SAM-functionalized substrates confirm that
      mechanically robust, long-chain organic silane SAMs can be formed on HF-treated
      Si3N4 tips without the presence of an intervening oxide layer. Adhesion
      experiments show that the integrity of the organic film on the chemically
      modified tips is maintained over repeated measurements and that the
      functionalized tips can be used for chemical sensing experiments since strong
      discrimination between different surface chemistries is possible.

PMID- 15969407
TI  - Is the wall of a cellulose fiber saturated with liquid whether or not permeable
      with CO2 dissolved molecules? Application to bubble nucleation in champagne
      wines.
AB  - In this paper, the transversal diffusion coefficient D perpendicular of CO2
      dissolved molecules through the wall of a hydrated cellulose fiber was
      approached, from the liquid bulk diffusion coefficient of CO2 dissolved molecules
      modified by an obstruction factor. The porous network between the cellulose
      microfibrils of the fiber wall was assumed being saturated with liquid. We
      retrieved information from previous NMR experiments on the self-diffusion of
      water in cellulose fibers to reach an order of magnitude for the transversal
      diffusion coefficient of CO2 molecules through the fiber wall. A value of about D
      perpendicular approximately 0.2D0 was proposed, D0 being the diffusion
      coefficient of CO2 molecules in the liquid bulk. Because most of bubble
      nucleation sites in a glass poured with carbonated beverage are cellulose fibers
      cast off from paper or cloth which floated from the surrounding air, or remaining
      from the wiping process, this result directly applies to the kinetics of carbon
      dioxide bubble formation from champagne and sparkling wines. If the cellulose
      fiber wall was impermeable with regard to CO2 dissolved molecules, it was
      suggested that the kinetics of bubbling would be about three times less than it
      is.

PMID- 15969408
TI  - Macroscopic alignment of graphene stacks by Langmuir-Blodgett deposition of
      amphiphilic hexabenzocoronenes.
AB  - We present structural studies of Langmuir (L) and Langmuir-Blodgett (LB) films of
      new amphiphilic hexa-peri-hexabenzocoronene (HBC) discotics, carrying five
      branched alkyl side chains and one polar group. The polar group is either a
      carboxylic acid moiety or an electron acceptor moiety (anthraquinone). Grazing
      incidence X-ray diffraction (GIXD) and X-ray reflectivity, both utilizing
      synchrotron radiation, show that these amphiphilic HBCs form well-defined
      Langmuir monolayers at the air-water interface, with a pi-stacked columnar
      structure where the HBC cores are rotated around the surface normal and tilted
      relative to the water surface. The intercolumnar distance is 20 A. The HBCs are
      confined to a layer lying on top of the layer of polar groups that are in contact
      with the water subphase. Efficient transfer of the monolayer of the anthraquinone
      substituted HBC derivative to hydrophobic quartz substrates by vertical dipping
      gave well-defined multilayer Y-type LB films. Polarized optical spectroscopy,
      GIXD, and X-ray reflectivity measurements show that the LB films consist of at
      least two phases. Heating the films results in an irreversible rearrangement to a
      single macroscopically aligned phase of hexagonally packed columns oriented along
      the dipping direction with disk planes perpendicular to the columnar axes and
      stacked in a cofacial manner. This phase transition is analogous to the
      reversible transition observed in the bulk material.

PMID- 15969409
TI  - Electrochemical characteristics of ferrocenecarboxylate-coupled aminoundecylthiol
      self-assembled monolayers.
AB  - The electrochemical characteristics of the modified electrodes with
      ferrocenecarboxylate-coupled aminoundecylthiol monolayers prepared in two
      sequential steps were studied. The self-assembled monolayer (SAM) was prepared
      through the covalent attachment of ferrocenecarboxylate in an activation solution
      containing N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide coupling agent to
      aminoundecylthiol SAMs formed on a substrate. In the ferrocenecarboxylate-coupled
      aminoundecylthiol monolayers, the ferrocene moieties were expected to be packed
      regularly with enhanced ordering compared with those in the FcCOO(CH2)11SH
      monolayer. As the ferrocene coverage increases, the formal potential for the
      ferrocene-ferricenium (Fc/Fc+) couple shifts to the positive potential and the
      full width at half-maximum (deltaE(fwhm)) increases also. The maximum coverage is
      found to be about 3 x 10(-10) mol cm(-2), which is considered to be a value
      obtained from a well-ordered ferrocene-tethered SAM. As for the mass change, the
      increase in ferrocene coverage caused the enhancement in ion association between
      the ferricenium cations and perchlorate anions resulting in a mass increase upon
      oxidation; however, the mass change per mole electron decreases. The results
      obtained from the ferrocenecarboxylate-coupled aminoundecylthiol monolayers were
      explained to be due to the well-ordered packing with regular spacing compared
      with those of the FcCOO(CH2)11SH monolayer.

PMID- 15969410
TI  - Controlling cell adhesion on human tissue by soft lithography.
AB  - Soft lithographic techniques are widely used for fundamental biological
      applications. This study investigates the extension of soft lithography for use
      on human tissue to create a biological implant by systematically studying the
      effect of pattern size on cellular morphology. We focus on mimicking a key layer
      of the physiological retina with an organized monolayer of epithelial cells to
      act as a new treatment for age-related macular degeneration. We show that
      epithelial cells can be confined to cytophilic islands defined on lens capsule by
      the inhibitory polymer poly(vinyl alcohol). In addition, as the size of the
      cytophilic islands grows, both the fraction of islands with cells attached and
      the number of cells adhered to each island increase. High densities of cell
      adhesion and single cell attachment per island were achieved with a 25 microm
      pattern size. Over time, the cells spread over the 5 microm wide barriers to form
      a confluent monolayer that may eventually serve as a functional retinal implant.
      With the ability to apply soft lithography to tissue samples, human tissue may
      become a universal membrane substrate for other ocular diseases or in tissue
      engineering applications elsewhere in the body.

PMID- 15969411
TI  - Interaction of bovine serum albumin and human blood plasma with PEO-tethered
      surfaces: influence of PEO chain length, grafting density, and temperature.
AB  - Solid surfaces are modified by grafting poly(ethylene oxide), PEO, to influence
      their interaction with indwelling particles, in particular molecules of bovine
      serum albumin and human plasma proteins. As a rule, the grafted PEO layers
      suppress protein adsorption. The suppression is most effective when the PEO layer
      is in a molecular brush conformation having a reciprocal grafting density (area
      per grafted PEO chain) less than the dimensions of the protein molecules.
      Nevertheless, the protein molecules may penetrate the PEO brush to some extent.
      For a given grafting density, the penetration is facilitated by increasing
      thickness of the brush. Tenuous brushes of reciprocal grafting densities
      exceeding the protein molecular dimensions enhance protein adsorption. The
      results point to a weak attractive interaction between PEO and protein. The
      protein repellency of a densely PEO-brushed surface is ascribed to a high
      activation energy for the protein molecules to enter the brush. Varying the
      temperature between 22 and 38 degrees C does not significantly affect the range
      of grafting density over which the brush changes from protein-attractive to
      protein-repellent.

PMID- 15969412
TI  - Nanoscale probing of the enamel nanorod surface using polyamidoamine dendrimers.
AB  - Although it is known that noncollagenous proteins of dental origin bind to the
      hydroxyapatite crystal surfaces, no measure of their binding strength has been
      calculated. This experiment used -COOH-capped generation 7 PAMAM dendrimers as
      nanoprobes of the biological hydroxyapatite nanorod surfaces. Dendrimer
      distribution was characterized using AFM. The results showed dendrimers to be
      spaced at intervals along the c-axis of the crystals. From these observations and
      assuming a fully ionized -COOH dendrimer, a mathematical model of the binding
      capacity of the crystal surface with the dendrimer was developed. The Monte Carlo
      method was used to simulate the binding process between the dendrimer and crystal
      surface, and the binding strength of the -COOH groups to the surface was
      calculated to be 90 +/- 20 kJ/mol. These results support the CFM studies which
      have described alternating bands of charge domains on the crystal surface and
      that the binding strength will be dependent on both the intensity of the charge
      on the protein and the crystal surface.

PMID- 15969413
TI  - Probing surface adhesion forces of Enterococcus faecalis to medical-grade
      polymers using atomic force microscopy.
AB  - The aim of this study was to compare the initial adhesion forces of the
      uropathogen Enterococcus faecalis with the medical-grade polymers polyurethane
      (PU), polyamide (PA), and poly(tetrafluoroethylene) (PTFE). To quantify the cell
      substrate adhesion forces, a method was developed using atomic force microscopy
      (AFM) in liquid that allows for the detachment of individual live cells from a
      polymeric surface through the application of increasing force using unmodified
      cantilever tips. Results show that the lateral force required to detach E.
      faecalis cells from a substrate differed depending on the nature of the polymeric
      surface: a force of 19 +/- 4 nN was required to detach cells from PU, 6 +/- 4 nN
      from PA, and 0.7 +/- 0.3 nN from PTFE. Among the unfluorinated polymers (PU and
      PA), surface wettability was inversely proportional to the strength of adhesion.
      AFM images also demonstrated qualitative differences in bacterial adhesion; PU
      was covered by clusters of cells with few cell singlets present, whereas PA was
      predominantly covered by individual cells. Moreover, extracellular material could
      be observed on some clusters of PU-adhered cells as well as in the adjacent
      region surrounding cells adhered on PA. E. faecalis adhesion to the fluorinated
      polymer (PTFE) showed different characteristics; only a few individual cells were
      found, and bacteria were easily damaged, and thus detached, by the tip. This work
      demonstrates the utility of AFM for measurement of cell-substrate lateral
      adhesion forces and the contribution these forces make toward understanding the
      initial stages of bacterial adhesion. Further, it suggests that initial adhesion
      can be controlled, through appropriate biomaterial design, to prevent subsequent
      formation of aggregates and biofilms.

PMID- 15969414
TI  - Effect of ionic strength on the binding of alpha-chymotrypsin to nanoparticle
      receptors.
AB  - Negatively charged carboxylate-functionalized mixed monolayer protected clusters
      (MMPCs) effectively bind and inhibit alpha-chymotrypsin based on complementary
      electrostatic surface recognition. We demonstrate that this binding can be
      disrupted by varying the ionic strength of the medium. Enzyme activity in the
      presence of MMPCs increases from 5% to 97% of native activity as salt
      concentration is increased from 0 to 1.5 M. Variation of ionic strengths after
      complete binding over 13 h results only in a modest restoration of enzymatic
      activity (< 35%). The conformation of chymotrypsin was characterized using
      circular dichroism and fluorescence spectroscopy, correlating structure with
      enzymatic activity. This work provides a useful insight of the electrostatic
      influence on protein--MMPC interactions and can be applied toward MMPC-based
      controlled release of proteins in vivo.

PMID- 15969415
TI  - Electrophoretic properties of DNA-modified colloidal gold nanoparticles.
AB  - Oligonucleotide-modified gold nanoparticles are used in various kinds of
      colorimetric DNA targeting biosensors and nanoparticle assembly techniques.
      Herein we focus on how the size of 13 nm gold colloids changes upon DNA
      modification. We have performed a series of electrophoresis experiments of
      particles modified both thiol specifically and nonspecifically with single- and
      double-stranded oligonucleotides of different lengths (12- and 25-mers). Both
      unmodified and DNA-modified particles migrated at constant velocity in different
      concentrations of Metaphor agarose gels. Linear Ferguson plots were obtained for
      all samples, and on the basis of the Ogston model approach, we present how the
      particle size increases in different amounts depending on the oligonucleotide
      length, secondary structure, and type of modification (specific or nonspecific).
      Thiol specifically modified particles obtain a thicker DNA layer since the
      oligonucleotides are only anchored to the particle in one end and thus stand up
      from the surface more compared to nonspecifically modified ones, where the
      oligonucleotides tend to lay more or less flat on the surface with multiple
      adsorption points. However the thickness of the DNA layer for the thiol
      specifically modified particles is smaller than the length of a corresponding
      stretched oligonucleotide, suggesting a flexibility of the thiol-bound strands
      allowing them to tilt relative to the particle surface.

PMID- 15969416
TI  - Langmuir-Blodgett films of amphiphilic bis(tetrathiafulvalene) macrocycles with
      four alkyl chains.
AB  - Amphiphilic bis(tetrathiafulvalene) [bis(TTF)] macrocycles with four alkyl chains
      were fabricated as novel electrically active Langmuir-Blodgett (LB) films. Two
      TTF units were linked via [24]crown-8, [21]crown-7, and [18]crown-6 macrocycles,
      forming charge-transfer (CT) salts with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyano-p
      quinodimethane (F4-TCNQ) at the air-water interface and on solid substrates. The
      CT salt of the amphiphilic bis(TTF)-macrocycle having a [24]crown-8 ring system
      formed a uniform surface morphology on mica. Using single-crystal X-ray
      structural analysis, the layer structure between the hydrophobic chains and the
      one-dimensional pi-pi stack of the CT salt was confirmed. Our results show that
      the bis(TTF)-macrocycle was folded at the flexible [24]crown-8 moiety, forming
      intramolecular pi-pi dimer structures and one-dimensional intermolecular pi-pi
      stacks with F4-TCNQ dimers. The open-shell electronic structure of the LB films
      was determined by electronic spectra, electrical conductivity, and electron spin
      resonance analyses. Asymmetry was introduced into the bis(TTF)-macrocycle by
      changing the ring size from [24]crown-8 to [21]crown-7. The surface morphology of
      the CT salts with F4-TCNQ was established as two-dimensional round-shape domains
      on mica. Further reduction of the macrocyclic ring from [21]crown-7 to [18]crown
      6 resulted in a CT salt of the bis(TTF)-macrocycle with F4-TCNQ with a leaf-shape
      domain morphology and a typical dimension of approximately 1 microm2 on mica. In
      general, decreasing the macrocyclic ring size from [24]crown-8 to [21]crown-7 or
      [18]crown-6 affected the inter- and intramolecular interactions and the surface
      morphologies of LB films.

PMID- 15969417
TI  - Room temperature solution synthesis of monodispersed single-crystalline ZnO
      nanorods and derived hierarchical nanostructures.
AB  - In this work, we report a room temperature wet-chemical approach to synthesize
      highly regulated, monodispersed ZnO nanorods and derived hierarchical
      nanostructures. In particular, ZnO has been prepared into single-crystalline
      conical or prismatic nanorods, and various hierarchical structures such as
      hexagonally branched, reversed umbrella-type, and cactus-like ZnO nanostructures
      comprising individual c-oriented nanorods. Depending on the synthetic conditions
      used, the diameter of nanorods can be controlled with a size down to 10-30 nm,
      while the aspect ratio can be controlled up to 50-100. Various preparative
      parameters, such as initial reactant concentrations, solvents, ligands,
      surfactants, precursor salts, and reaction time, have been systematically
      examined. Due to slow reactions at room temperature, excellent crystallinity and
      high morphological yield (100% in most cases) have been achieved via tuning the
      synthetic parameters. Our photoluminescence and UV measurements also confirm the
      attained crystal perfection and size uniformity.

PMID- 15969418
TI  - Effect of additives on the photovoltaic performance of coumarin-dye-sensitized
      nanocrystalline TiO2 solar cells.
AB  - The effects of deoxycholic acid (DCA) and 4-tert-butylpyridine (TBP) as additives
      on the photovoltaic performance of coumarin-dye-sensitized nanocrystalline TiO2
      solar cells were investigated. DCA coadsorption improved both the photocurrent
      and photovoltage of the solar cells, even though it decreased the amount of dye
      adsorbed on the TiO2 electrode. The improved photocurrent may arise from
      suppression of the deactivation of the excited state via quenching processes
      between dye molecules or a more negative LUMO level of the dye in the presence of
      DCA, resulting in a high electron-injection yield from the dye into TiO2. The
      increased photovoltage is probably due to suppression of recombination between
      the injected electrons and I3- ions on the TiO2 surface (dark current). The
      addition of TBP to the electrolyte also markedly improved the photovoltage and
      fill factor of the solar cell, and consequently, the total conversion efficiency
      increased from 3.6% to 7.5%. FT-IR spectroscopy indicated that a large amount of
      TBP was adsorbed on the dye-coated TiO2 films in the presence of Li cations. This
      result suggests that TBP, like DCA, suppressed the dark current on the TiO2
      surface, which resulted in the improved photovoltage.

PMID- 15969419
TI  - Deposition of cationic polymer micelles on planar SiO2 surfaces.
AB  - The deposition of PS-PVPH+ polymer micelles from a pH 1 aqueous solution onto Si
      wafers has been studied using a simple dip-coating technique. It has been found
      that the rate of evaporation of the solvent and the rate of withdrawal have a
      considerable influence on the density and ordering of the adsorbed micelles. The
      highest density and degree of ordering (as judged by the 2D pair correlation
      function) is achieved when solvent evaporation dominates the deposition process,
      but a fairly homogeneous distribution of polymer micelles can be achieved over a
      distance of at least 3-4 mm by controlling the solvent evaporation rate and the
      rate of substrate withdrawal. We did not observe any significant effect of added
      KCl (up to 0.1 M) during the deposition process or soaking in 1 M KCl after
      deposition. The attachment of these micelles is quite robust, as they cannot be
      washed off in pH 1 water (with or without KCl) without significant mechanical
      assistance. However, we did find that the micelles are rather easily caused to
      dewet and partially aggregate under the influence of 65 degrees C water vapor.

PMID- 15969420
TI  - The dominant role of solvent in the sequestering of bile salts by hydrophobic
      cationic polymeric resins.
AB  - The binding behavior of sodium cholate, a trihydroxy hydrophobic bile salt, by a
      polyacrylamide resin with N,N,N-trimethylammonium dodecyl chloride (QPDA12)
      pendant group was determined with varying buffer conditions and in the presence
      of 1,2-propanediol as a solvent perturbant. Binding constants extracted from the
      fit of the binding isotherms to the Langmuir equation were obtained at several
      temperatures. The temperature dependence of the binding behavior indicated that
      binding, in comparison with that of the dihydroxy chenodeoxycholate, was weaker
      due to a smaller positive entropic change, despite a lowered enthalpic barrier.
      Enthalpy-entropy compensation with a compensation temperature of 285-290 K,
      characteristic of processes involving water, was found to encompass both the
      cholate and chenodeoxycholate data under a wide variety of conditions. Previous
      studies with sodium chenodeoxycholate determined that loss of hydrophobic
      hydration within the resin dominated the thermodynamics of the binding process,
      but the observations with sodium cholate revealed that solvent liberation about
      the bile salt is also a contributor.

PMID- 15969421
TI  - Ethylene glycol monolayer protected nanoparticles: synthesis, characterization,
      and interactions with biological molecules.
AB  - The usefulness of the hybrid materials of nanoparticles and biological molecules
      on many occasions depends on how well one can achieve a rational design based on
      specific binding and programmable assembly. Nonspecific binding between
      nanoparticles and biomolecules is one of the major barriers for achieving their
      utilities in a biological system. In this paper, we demonstrate a new approach to
      eliminate nonspecific interactions between nanoparticles and biological molecules
      by shielding the nanoparticle with a monolayer of ethylene glycol. A direct
      synthesis of di-, tri-, and tetra(ethylene glycol)-protected gold nanoparticles
      (Au-S-EGn, n = 2, 3, and 4) was achieved under the condition that the water
      content was optimized in the range of 9-18% in the reaction mixture. With
      controlled ratio of [HAuCl4]/[EGn-SH] at 2, the synthesized particles have an
      average diameter of 3.5 nm and a surface plasma resonance band around 510 nm.
      Their surface structures were confirmed by 1H NMR spectra. These gold
      nanoparticles are bonded with a uniform monolayer with defined lengths of 0.8,
      1.2, and 1.6 nm for Au-S-EG2, Au-S-EG3, and Au-S-EG4, respectively. They have
      great stabilities in aqueous solutions with a high concentration of electrolytes
      as well as in organic solvents. Thermogravimetric analysis revealed that the
      ethylene glycol monolayer coating is ca. 14% of the total nanoparticle weight.
      Biological binding tests by using ion-exchange chromatography and gel
      electrophoresis demonstrated that these Au-S-EGn (n = 2, 3, or 4) nanoparticles
      are free of any nonspecific bindings with various proteins, DNA, and RNA. These
      types of nanoparticles provide a fundamental starting material for designing
      hybrid materials composed of metallic nanoparticles and biomolecules.

PMID- 15969422
TI  - Steady-state photocatalytic epoxidation of propene by O2 over V2O5SiO2
      photocatalysts.
AB  - A silica-supported, lowly loaded vanadium oxide (V2O5/SiO2) photocatalyst
      promotes the photocatalytic epoxidation of propene with O2 at steady state in a
      flow reactor system. Very little deep oxidation of propene into CO2 takes place
      over V2O5/SiO2, in contrast to the results obtained over a TiO2 photocatalyst in
      which total oxidation is the main path. With each loading, the sums of the
      selectivities into propene oxide (PO) and propanal (PA) at steady state were
      almost the same. The monomeric VO4 tetrahedral species dispersed on SiO2 yield PO
      under UV irradiation. The less dispersed vanadium oxide species on SiO2 promote
      the isomerization of PO into PA. We utilized a flow reactor system in which the
      short contact time reduced the isomerization and resultant decomposition of PO
      over the catalyst surface.

PMID- 15969423
TI  - Acetate stabilization of metal nanoparticles and its role in the preparation of
      metal nanoparticles in ethylene glycol.
AB  - Acetate-stabilized ruthenium nanoparticles were prepared by the NaBH4 reduction
      of the metal precursor salt at room temperature. Nanoparticles with a mean
      diameter of 2.20 nm and a standard deviation of 1.03 nm could be obtained under
      experimental conditions. The Ru nanoparticles so obtained could be easily
      extracted to a toluene solution of alkylamine, giving rise to alkylamine
      stabilized Ru nanoparticles with a mean diameter of 2.96 nm and a standard
      deviation of 0.92 nm. The new found role of acetate stabilization was used to
      formulate a mechanism for the formation of metal (Pt, Ru) nanoparticles in
      ethylene glycol. In this mechanism metal nanoparticles are stabilized in ethylene
      glycol by adsorbed acetate ions, which are produced as a product of the OH-
      catalyzed reaction between the metal precursor salt and ethylene glycol.

PMID- 15969424
TI  - Morphological and photoelectrochemical characterization of core-shell
      nanoparticle films for dye-sensitized solar cells: Zn-O type shell on SnO2 and
      TiO2 cores.
AB  - Core-shell type nanoparticles with SnO2 and TiO2 cores and zinc oxide shells were
      prepared and characterized by surface sensitive techniques. The influence of the
      structure of the ZnO shell and the morphology ofnanoparticle films on the
      performance was evaluated. X-ray absorption near-edge structure and extended X
      ray absorption fine structure studies show the presence of thin ZnO-like shells
      around the nanoparticles at low Zn levels. In the case of SnO2 cores, ZnO
      nanocrystals are formed at high Zn/Sn ratios (ca. 0.5). Scanning electron
      microscopy studies show that Zn modification of SnO2 nanoparticles changes the
      film morphology from a compact mesoporous structure to a less dense macroporous
      structure. In contrast, Zn modification of TiO2 nanoparticles has no apparent
      influence on film morphology. For SnO2 cores, adding ZnO improves the solar cell
      efficiency by increasing light scattering and dye uptake and decreasing
      recombination. In contrast, adding a ZnO shell to the TiO2 core decreases the
      cell efficiency, largely owing to a loss of photocurrent resulting from slow
      electron transport associated with the buildup of the ZnO surface layer.

PMID- 15969425
TI  - Spectroscopic characterizations of molecularly linked gold nanoparticle
      assemblies upon thermal treatment.
AB  - The understanding of surface properties of core-shell type nanoparticles is
      important for exploiting the unique nanostructured catalytic properties. We
      report herein findings of a spectroscopic investigation of the thermal treatment
      of such nanoparticle assemblies. We have studied assemblies of gold nanocrystals
      of approximately 2 nm core sizes that are capped by alkanethiolate shells and are
      assembled by covalent or hydrogen-bonding linkages on a substrate as a model
      system. The structural evolution of the nanoparticle assemblies treated at
      different temperatures was probed by several spectroscopic techniques, including
      UV-visible, Fourier transform infrared (FTIR), and X-ray photoelectron
      spectroscopy (XPS). The results show that the capping/linking shell molecules can
      be effectively removed to produce controllable surface and optical properties.
      The data further revealed that the thermally induced evolution of the surface
      plasmon resonance property of gold nanoparticles is dependent on the chemical
      nature of the linker molecule. The spectral evolution is discussed in terms of
      changes in particle size, interparticle distance, and dielectric medium
      properties, which has important implications for controlled preparation and
      thermal processing of core-shell nanostructured metal catalysts.

PMID- 15969426
TI  - Amphiphilic properties of poly(oxyalkylene)amine-intercalated smectite
      aluminosilicates.
AB  - Layered aluminosilicates, including synthetic fluorine mica and natural
      montmorillonite (MMT), were intercalated with poly(oxypropylene)-polyamine
      quaternary salts with a 230-5000 molecular weight range. The X-ray basal spacing
      of these silicates had been expanded from 13.5 to 83.7 A for the synthetic mica
      and to 92.0 A for MMT. The relative silicate dimensions (300-1000 nm for
      synthetic mica and 80-100 nm for MMT) were ascertained by direct TEM observations
      in the case of the co-intercalated synthetic mica and MMT mixtures with Mw = 2000
      quaternary ammonium salts. The tailored organic incorporation of synthetic mica
      and MMT clays could alter these hydrophilic clays, making them amphiphilic, and
      enable the lowering of toluene/water interfacial tension to 2.0 mN/m at the
      critical concentration of 0.1 wt %.

PMID- 15969427
TI  - Effects of the SO4 groups on the textural properties and local order deformation
      of SnO2 rutile structure.
AB  - Sulfated tin oxide was synthesized from a hydroxylated tin oxide obtained by the
      precipitation method, followed by ion exchange of OH groups by SO4 species with a
      sulfuric acid solution. The samples were characterized by X-ray diffraction,
      transmission electron microscopy, thermoanalysis, and nitrogen physisorption by
      the Brunauer-Emmett-Teller method. The rutile crystalline structure was refined
      by the Rietveld method. Thermal analysis suggests the following stoichiometric
      formulas: SnO2-x(OH)2x and SnO2-x(OH)x(HSO4)x with X = 0.35 and 0.17 for non
      sulfated and sulfated samples, respectively. The SO4 species remained strongly
      bonded at the SnO2 surface stabilizing its crystallite size against sintering,
      inhibiting the crystallite aggregation, and it acts as a structure porogen
      director mediating nanoparticle growth and assembly yielding a mesostructure form
      of SnO2 with wormhole morphology and high thermal stability. The interaction
      between SO4(2-) and the SnO2 surface changes the symmetry of the representative
      tin-oxygen octahedron. It relaxes the four tin-oxygen bond lengths located at the
      basal plane of the octahedron while the two apical Sn-O bonds decrease, producing
      a strong deformed octahedron, which could be transformed into a higher asymmetry
      in the electronic distribution around the Sn4+ nuclei. The elimination of SO4
      groups brings about the coalescence and crystallite growth, which collapse the
      mesostructure form of SnO2, decreasing the surface area and porosity.

PMID- 15969428
TI  - Gelation of concentrated micellar solutions of a triblock copolymer of ethylene
      oxide and styrene oxide, S5E45S5.
AB  - Triblock copolymer S5E45S5 was synthesized by oxyanionic polymerization of
      styrene oxide initiated by a preformed difunctional polyethylene glycol. Here E
      denotes OCH2CH2, S denotes OCH2CH(C6H5), and the subscripts denote number-average
      block lengths in repeat units. Previous work on the closely related copolymer
      S4E45S4 indicated that micelles would form in aqueous solutions of copolymer
      S5E45S5, and that they would undergo transient intermicellar bridging. Dynamic
      light scattering was used to confirm this. Rheometry and small-angle X-ray
      scattering were used to explore gel boundaries, structures, and properties. At
      moderate copolymer concentrations (14 and 20 wt %) measurements of the dynamic
      shear moduli indicated the formation of low-modulus soft gels attributed to
      spherical micelles forming transient networks. A region of low storage modulus at
      c approximately 30 wt % preceded a change to hard gel. A 40 wt % hard gel was
      disordered, while at higher concentrations (49 and 60 wt %) the micelles packed
      into hexagonal structures with high values of the storage modulus (G'
      approximately 10 kPa at 25 degrees C and 1 Hz).

PMID- 15969429
TI  - Monte Carlo simulation of properties of monolayers and metal islands adsorbed on
      metallic (111) surfaces.
AB  - To obtain the surface stress changes deltasigma due to the adsorption of metal
      monolayers onto metallic surfaces, a new model derived from thermodynamic
      considerations is presented. Such a model is based on continuum Monte Carlo
      simulations with embedded atom method potentials in the canonical ensemble, and
      it is extended to consider the behavior on different islands adsorbed onto (111)
      substrate surfaces. Homoepitaxial and heteroepitaxial systems are studied.
      Pseudomorphic growth is not observed for small metal islands with considerable
      positive misfit with the substrate. Instead, the islands become compressed upon
      increase of their size. A simple model is proposed to interpolate between the
      misfits of atoms in small islands and the pseudomorphic behavior of the
      monolayer.

PMID- 15969430
TI  - Adsorption/desorption hysteresis in inkbottle pores: a density functional theory
      and Monte Carlo simulation study.
AB  - The mechanisms of adsorption and desorption in inkbottle-shaped pores are
      considered for lattice models using grand canonical mean field density functional
      theory and Monte Carlo simulation. We find that they depend significantly on the
      particular pore geometry, the nature of the fluid-solid interaction, and the
      temperature. We find two mechanisms for desorption. One mechanism involves the
      emptying of the main cavity even as the density of fluid in the necks remains
      high, a mechanism observed recently in studies of an off-lattice model of an
      inkbottle. The other is a simultaneous desorption from the entire pore space,
      behavior that is more closely related to the traditional picture of pore blocking
      in the inkbottle system.

PMID- 15969431
TI  - Photochemistry and patterning of monolayer films from 11
      phenylundecyltrichlorosilane.

PMID- 15969432
TI  - Photodegradation micropatterning of adsorbed collagen by vacuum ultraviolet
      light.

PMID- 15969433
TI  - Construction of cell-resistant surfaces by immobilization of poly(ethylene
      glycol) on gold.

PMID- 15969434
TI  - Microstructure and physical properties of a pH-responsive gel based on a novel
      biocompatible ABA-type triblock copolymer.

PMID- 15969435
TI  - [EEG frequency: amplitude characteristics at different levels of consciousness].
AB  - Relationship was studied between the level of consciousness and the level of the
      brain activation. State of transition from wakefulness to drowsiness was used as
      a model of gradual decrease in the level of consciousness. A change in the
      intensity and quality of appearing involuntarily mental processes served as an
      index of the level of consciousness as determined by subjects' self-reports. It
      was found that a certain EEG profile corresponded to each level of consciousness
      under study. The data obtained showed that the lowest level of activation
      corresponded to a state in which a subject develops inhibition of "internal
      speech", "failure of thoughts". In this case, the dynamics of the EEG high
      frequency rhythm changes was possibly related to the mechanism of transmission of
      cognitive information.

PMID- 15969436
TI  - [Two phases of the contingent negative variation in humans: connection with motor
      and mental functions].
AB  - The question of dependence of the contingent negative variation (CNV) on the
      regulating mechanisms of motor and mental functions is not sufficiently studied.
      The tasks of the present work were: to investigate the dependence of the CNV
      early and late phases on the state of motor and mental functions in patients with
      Parkinson's disease (PD), and to elucidate the levodopa influence on the CNV
      parameters. 18 healthy subjects and 56 patients with PD were studied. In PD
      patients, significant reductions of amplitudes and squares of two CNV phases were
      observed. A negative correlation of the degree of coordinating muscle
      relationships disturbance with amplitudes of two CNV phases was found (p < 0.01).
      A positive interdependence between values of the both CNV phases and the state of
      mental functions was established, memory in particular (p < 0.05). After levodopa
      administration in PD patients, the early CNV phase did not significantly change,
      whereas the late CNV phase significantly increased (p < 0.05). Results of the
      investigation suggest an important role of the structures ensuring both direct
      motor control and mental functions in two CNV phases formation. A more obvious
      levodopa influence on the late CNV phase suggest participation of the basal
      ganglia efferent system in generation of the late CNV phase rather than in
      organization of the early CNV phase.

PMID- 15969437
TI  - [The action of proinflammatory cytokines on formation of behavior during early
      postnatal ontogenesis].
AB  - The study is devoted to the role of proinflammatory cytokine-interleukin-1beta
      during early postnatal ontogenesis in formation of behavioral programs. Cytokine
      was injected in pyrogenic and subpyrogenic doses during 1 week (1, 2 or 3 weeks
      of life). The behavior was tested in the young (40-45 days) and adult (3 months)
      rats in the "open field" and "elevated plus maze". The greatest behavior disordes
      (elevation of act's number and of motor activity, the decrease of investigation
      activity) are revealed in the young animals treated with IL-Ib during 1 and 3
      weeks of life. These behavioral changes were marked in rats injected with
      pyrogenic and subpyrogenic doses of cytokine. They had a similar tendency in male
      and female rats. At the age of 3 months, behavior changes revealed in juvenile
      rats were insignificant.

PMID- 15969438
TI  - [The degree of cerebal oxidative stress in rats during ischemia-reperfusion
      combined with a modulaion of L-arginine-NO system].
AB  - We estimated the cerebral oxidative stress during ischemia-reperfusion of the
      brain in conditions of modulated L-arginine-NO system in rats. In 128 rats, the
      changes in lipid peroxidation products (conjugated dienes, malondialdehyde,
      Schiff bases) and antioxidant defense factors (retinal, a-tocopherol, SH-groups)
      were studied. Analysis of the inhibitor (administration of NO synthase substrate
      L-arginine, non-selective inhibitor Nw-nitro-L-arginine methyl ester, selective
      inhibitor of neuronal NO synthase 7-nitroindasole, or selective inhibitor of
      inducible NO synthase S-methyl-isothiourea) showed the NO-dependent nature of
      oxidative stress in rats with brain ischemia-reperfusion. NO generated by
      different NO synthase isoenzymes played different roles: hyperactivation of the
      neuronal NO synthase was associated with oxidative stress during both brain
      ischemia-reperfusion periods, and the higher inducible NO synthase activity had
      such association only during the later period.

PMID- 15969439
TI  - [Effect of rarely repeated immobilization episodes on hypoxia-tolerance and
      anxiogenic stress severity].
AB  - 4 episodes of immobilization stress (60 minutes, once 72 hours) led to diminution
      of hypoxia tolerance and anxiety-depressive disorders of behavior. The later
      shifts were associated with decrease of IL-4 concentration and simultaneous
      increase of IL-6 level in blood serum. The stress-induced behavioral shifts
      appeared to correlate with IL-4 concentration in blood of stress-sustained rats.

PMID- 15969440
TI  - [Hypophysis--thyroid gland--gonads in boys of the pubertate period in south areas
      of Archangelsk region].
AB  - The hormonal level dynamics of hypophysis, thyroid gland and sex steroids was
      analyzed in respect to the puberty. Concentrations of gonadotropins and sex
      streroids were increased whereas concentrations of thyroid hormones was
      decreased. The amplitude of hypophysis and thyroid hormones were narrowed whereas
      the range of sex steroids was extended during the puberty. In early stages of
      puberty, the interhormonal correlations existed on some levels (hypophysis or
      peripheral gland), but in late stage the intersystem and polyhormonal relations
      were formed. Thyroid hormones play a leading role in sexual maturity regulation.
      The sexual maturity is prolonged, the variance of sexual stages being quite wide.
      The range of gonadotropin shifted to the left side in comparison with children in
      moderate latitudes.

PMID- 15969441
TI  - [Experimental comparative evaluation of the functional capacities of ectopically
      grown fetal organs].
AB  - The interest for fetal organ, tissue, and cell implantation as therapeutic means
      in the treatment of some diseases is presently increasing. Hence, the aim of the
      present investigation was the comparative evaluation of the functional potential
      of ectopically grown fetal organs of different (ecto-, meso- and endodermic)
      origins. Unified operative model was the fetal organ fragment implantation into
      an ear subcutaneous pouch (without restoration of vascular and nervous links of
      the implant with the recipient organism). The implant isolation in vitro varied
      from 15 to 50 min. As control, intact animals and animals with streptozotocin
      diabetes and hepatic lesions due to the main bile duct ligature, were used. The
      implanted and ectopically grown fetal organs, though of different origins,
      developed functional activity. The best adult-like function was obtained in
      intestinal, gastric and cardiac implants, i.e. in organs with a cavity and a well
      developed self-regulation system. Poorer results were obtained in great digestive
      glandular implants--pancreas and liver. In the best cases when the implant
      function was very closed to the adult organ, a difference nevertheless was
      observed. The model of ectopic implantation of fetal organs may be useful for
      study of the organ and tissue function ontogenesis (up to the moment of natural
      ageing involution), for the evaluation of different isolated factor influence on
      organ and tissue physiology and pathology. Although being optimistic in respect
      to clinical application of fetal organ and cell implantation, this study does not
      prevent us from being cautions.

PMID- 15969442
TI  - [Compensatory-adaptive responses of the rabbit fetuses developed under different
      intrauterine conditions, to noradrenaline administration].
AB  - In 9 experimental rabbit fetuses (with reduced uterine-placental blood frow),
      noradrenaline administration led to an obvious thermogenic response and heart
      rate increase, but not in intact rabbits. Obviously the noradrenaline dosage
      corresponds to the range of adaptive capacities of the functional systems in
      intact fetuses and so does not induce any shifts of the homeostasis parameters in
      them. The experimental fetuses prove to be more vulnerable to stresses, and
      homeostasis parameter shifts in them are statistically significant.

PMID- 15969443
TI  - [Mechanisms of serotonin effect on motility of ileocaecal zone in alert rabbits].
AB  - I.V. administration of serotonin (2 mg kg(-1)) to alert rabbits changed the
      ileal, caecal, and colon motility including excitatory and inhibitory components.
      Initial rise of contractile activity was quickly replaced by its diminishing
      followed by a longer enhancement of the motility, and then by the final,
      inhibitory, phase. Under blockade of beta1- and beta2-adrenoreceptors with
      propranolol inhibition of ileal and caecal contractile activity with serotonin
      was preserved, the effect of circulating catecholamines on beta-adrenoreceptors
      of smooth muscle cells seems to be excluded as a cause of the serotonin
      inhibitory effect. In conditions of blockade of pre- and postsynaptic alpha
      adrenoreceptors with phentolamine, there was no significant diminishing of the
      contractile activity in the ileo-caecal zone below the initial level induced by
      serotonin in control experiments. Intensification of the ileo-caecal zone
      contractile activity under the effect of serotonin persisted in conditions of
      blockade of muscarinic cholinoreceptors and was proceeding with participation of
      non-cholinergic excitatory mechanism.

PMID- 15969444
TI  - [Beritashvili's theory of the role of images in regulation of behaviour, and the
      modern neurosciences].

PMID- 15969445
TI  - [The history of organization and development of Pavlovian clinics at the
      Institute of Experimental Medicine St. Petersburg].

PMID- 15969447
TI  - Immunostimulatory and immunomodulatory peptides derived from the alpha1 domain of
      HLA-B27 in experimental autoimmune diseases in Lewis rats.
AB  - Peptides derived from amino acid sequence 60-80 of HLA-B27 (B27PA, aa 60-72 and
      B2702PA, aa 60-80) mimic cytokeratin and are able to induce in vitro
      proliferation of human peripheral blood lymphocytes as well as arthritis in Lewis
      rats. Here we show that the pathogenic epitope recognized by autoaggressive rat T
      cells is located at the N-terminus of the sequence, between aa 60 and 72. A C
      terminally elongated 25mer peptide (B2702.60-84) showed increased pathogenicity,
      indicating either a second arthritogenic epitope or an immunomodulatory region
      within this peptide. B2702.60-84 has been described to inhibit murine and human
      CD8 + cytotoxic T cells (CTL) and was even successfully used for the treatment of
      allograft rejection. In addition to pathogenicity we have investigated the
      immunomodulatory effect of peptide B2702.60-84 in our rat model of experimental
      autoimmune uveitis (EAU), induced with retinal S-Antigen peptide PDSAg. We found
      that disease exacerbated following coimmunization of PDSAg with B2702.60-84. In
      vitro, the B27-peptide enhanced the proliferation of CD4+ T cell lines specific
      for retinal autoantigen peptides during coincubation of B2702.60-84 with the
      respective antigen. Oral tolerance induction, an effective mechanism to prevent
      uveitis in Lewis rats, is abrogated by cofeeding peptide B2702.60-84 with the
      tolerogen PDSAg. In rat EAU, naturally occurring regulatory T cells and orally
      induced gamma deltaTCR+ suppressor cells are CD8+ which might be impeded by
      peptide B2702.60-84. As a consequence of their abrogated suppressive capacity
      disease was exacerbated. We propose a similar role of HLA-B27 in man: disturbing
      the mechanisms down-regulating self-responses might lead to autoimmune diseases.
      This could explain the high association of HLA-B27 with a variety of autoimmune
      diseases targeting different organs or tissues.

PMID- 15969446
TI  - Effect of dietary fat on skin reactivity against histamine, Th1 and Th2 cytokine
      levels and some serum parameters in mice.
AB  - Changes in diet may be associated with the increase in allergic disease; change
      to high-calorie and high-fat diets may be a factor. In this study our objective
      was to determine skin reactivity of histamine and serum cytokine concentrations
      in mice fed diets containing different amounts of fat. Histamine reactivity was
      performed on mice back skin and serum cytokine concentrations were measured by
      ELISA in mice injected with anti-CD3 antibody. We measured serum interferon-gamma
      as a Th1-type cytokine and interleukin-4 as a Th2-type cytokine. Mice fed a high
      fat diet displayed enhanced skin reactivity of histamine and higher IL-4 levels
      in serum. These data suggest that a high fat diet may play a role in enhancing
      allergic reactions.

PMID- 15969448
TI  - Perforin improves the morphogenesis of mouse placenta disturbed by IL-2
      treatment.
AB  - The pore-forming protein (perforin) produced by lymphocytes can induce apoptosis
      in target cells. In mouse placenta, although a large amount of perforin is
      produced by the uterine natural killer (uNK) cells, its role in the reproductive
      process is still not clear. Since the cytotoxicity of uNK cells can be enhanced
      by interleukin (IL)-2, we studied the role of perforin in the placenta of wild
      type and perforin-knockout mice treated with IL-2 during days 10-14 of pregnancy.
      Immunohistochemistry of the wild-type mice showed that the perforin was positive
      in the membrane of trophoblast glycogen cells as well as the cytoplasm of uNK
      cells, and there was an increase in the expression level following IL-2 treatment
      as revealed by RT-PCR analysis, although no change was identified in fertility.
      In the IL-2-treated perforin-knockout mice, however, the number of live fetuses
      was decreased, accompanied by an increase in the weight of placentae. Examination
      of these placentae showed an abnormally enlarged junctional zone, occupied by a
      large number of the trophoblast glycogen cells and significantly few of the
      apoptotic cells. These findings indicate that perforin can contribute to a
      successful pregnancy by inhibiting the excessive growth of the junctional zone
      induced by IL-2.

PMID- 15969449
TI  - Heat shock protein 27 expression in patients with chronic liver damage.
AB  - The aim of this study was to evaluate a possible relationship between
      lymphomonocyte expression of heat shock proteins (HSP) 60/27 and plasma levels of
      pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) and
      markers of antioxidant/oxidative status [glutathione (GSH), alpha glutathione-S
      transferase activity (alpha GST), malonyldialdeyde (MDA), 4-hydroxinonenal (4
      HNE), and S-nitrosothiols (S-NO)] in patients with chronic liver diseases.
      Entered into the study were 47 subjects: 10 healthy controls, 16 patients with
      HCV-related chronic hepatitis (CH), and 16 patients with HCV-related and 5 with
      alcohol-related liver cirrhosis (10 Child A and 11 Child B+C). HSP60 was clearly
      expressed only in 5% of patients and lowly in the control group. HSP27 was
      clearly expressed in 46.7% of CH and 71.4% of cirrhotic patients but was lowly
      present in healthy subjects. A significant difference was found between patients
      with a low expression of HSP27 (negative patients) and those with a high HSP27
      expression (positive patients) of plasma levels both of antioxidants (GSH, p <
      0.05), and of markers of enhanced production of free radicals and cytokines
      (alpha GST, TNF-alpha and IL-6, p < 0.05; MDA, 4-HNE and S-NO, p < 0.01) as well
      as for alcohol use and degree of liver impairment. The present data are the first
      showing that, particularly in conditions of enhanced oxidative stress,
      lymphomonocytes from liver disease patients present an increased expression of
      HSP27.

PMID- 15969450
TI  - Ligaria cuneifolia flavonoid fractions modulate cell growth of normal lymphocytes
      and tumor cells as well as multidrug resistant cells.
AB  - Flavonoids are ubiquitous compounds present in plant extracts. They represent a
      major active component of the plant extract and are often known for their anti
      inflammatory and anti-tumor effects. Previously, we demonstrated that Ligaria
      cuneifolia (R et P) Tiegh. (Loranthaceae) extracts inhibit proliferation of
      murine mitogen-activated lymphocytes as well as murine T leukaemia (LB) and
      breast tumor cells (MMT). The aim of this study was to assess the anti
      proliferative and pro-apoptotic activities of three separate flavonoid fractions
      derived from L. cuneifolia whole extract (aqueous, methanolic and ethyl acetate)
      on normal and tumor cells. This was performed as a bio-guided approach leading to
      the isolation and identification of the active compounds responsible for the
      effects observed with the whole extract. Results showed that the three fractions
      differed in the amount and type of compounds found. Only the ethyl acetate
      flavonoid fraction (100 microg/ml) was able to inhibit significantly the
      proliferation of Con A stimulated splenocytes or LB and MMT cells. Inhibition of
      proliferation was mediated by apoptosis as determined by morphology and DNA
      hypodiploidy. The ethyl acetate fraction modified mRNA expression of IL-2, IL-10
      and TGF-beta, while the methanol fraction only modified IL-10 mRNA on LB cells.
      Our results show that the ethyl acetate flavonoid fraction contains the most
      active compound/s and is the potential candidate to isolate the active compound/s
      responsible for the effects observed with L. cuneifolia whole extract.

PMID- 15969451
TI  - Epidemiology and microbiology at the National Institute of Public Health, Prague,
      Czech Republic.

PMID- 15969452
TI  - Epidemiologic characteristics of hypertension in the civilians of Kosovo after
      the war.
AB  - 34th Greek regimen, which was part of the NATO forces, provided medical services
      to the civilians of Kosovo. We studied epidemiologic data in the population of
      Kosovo regarding hypertension in order to determine the prevalence and
      characteristics of hypertension. 830 patients (281 - 33.86% male, 62 +/- 26 yrs
      and 549 - 66.14% female, 49 +/- 28 yrs) were examined for different diseases. We
      identified 254 (30.6%) patients with hypertension (188 female and 66 male).
      According to the international criteria used for the classification of the
      severity of hypertension, more than half of the patients (51.2%) had severe
      hypertension, 31.5% modest and 17.3% mild. Statistically significant relation
      between the severity of hypertension and age or sex was not found out. Increased
      BMI as well as the presence of proteinuria and rheumatic diseases were
      significantly related to the severity of the hypertension while the coexistent
      heart disease, diabetes mellitus and chronic obstructive pulmonary disease (COPD)
      wasn't. The use of non-steroid anti-inflammatory agents (NSAIDs) was related to
      the severity of hypertension with a borderline significance. 31.4% of the
      patients were on treatment with NSAIDs and/or cortisone because of rheumatic
      disease or obstructive pulmonary disease. Overfunction of the sympathetic system
      was present in 62.99%. The mean heart rate was greater in women (84/min) than in
      men (72/min). 28.35% of the patients had secondary hypertension, including the
      patients on a drug that can elevate the blood pressure and patients with
      increased activity of the sympathetic nervous system. So, 8.6% of the patients
      had usual causes of secondary hypertension and 19.6% hypertension secondary
      related to the use of NSAIDs or cortisone, or due to the increased activity of
      the sympathetic nervous system. Antihypertensive treatment was started in 248
      patients, i.e. in all of them except the ones already on treatment having their
      blood pressure well controlled. For antihypertensive treatment beta-blockers or
      central adrenergic inhibitors either as monotherapy or in combination with other
      agents were used most frequently combined with diuretics and Ca antagonists and
      ACE inhibitors. In conclusion the diagnosis and treatment of hypertension in the
      population of Kosovo during the post war period had certain particularities.

PMID- 15969453
TI  - Occupational accidents in Serbian industries in transition.
AB  - Occupational accidents and injuries present a serious social, medical and
      economical problem in Serbian industries in transition. The purpose of this study
      is to estimate the number and average annual rate of occupational accidents and
      traumatic injuries in Serbian industries in transition, between 1992 and 2003,
      and to estimate the effects of a preventive safety program in the rubber
      manufacturing industry and in the production of electrical goods and equipment.
      This paper presents a descriptive analysis of occupational accidents and injuries
      which occurred in all industries over a twelve years period. In the rubber
      manufacturing industry and in the production of electrical goods and equipment a
      surveillance and prevention program has been implemented since 1997. A
      significant drop after 1997 in average annual accidents rate and severity ratio
      of injuries in these two industries has been observed, which was not the case in
      the other industries, and can be explained by the positive effects of the safety
      training program. The study documents that the safety training program showed
      significant effects, especially in case of workers with less than ten years of
      working experience.

PMID- 15969454
TI  - Validity and recall of information from questionnaires concerning respiratory
      infections among schoolchildren.
AB  - The aim of the study was to assess the reliability of questionnaire information
      on visits to a physician and the use of antibiotics taken for respiratory
      infections among schoolchildren attending a water-damaged school and a reference
      group of schoolchildren attending an undamaged school. Two similar questionnaires
      on respiratory morbidity in two consecutive years were sent to the parents. The
      information given on the questionnaires was compared with the patient's records
      of the local health centre. Although the overall total numbers of ambulatory
      visits in the patients' records and questionnaires seemed to indicate good
      reliability, a more detailed individual investigation showed poor recall validity
      from the questionnaires, including a high percentage of unreported visits to the
      local health centre from both schools. Underreporting was commoner in the control
      school than in index school. Recall was best for the children who had no visits
      to a doctor. Use of antibiotics had a better recall than ambulatory visits in
      both schools. The study indicates that information on health services in
      questionnaires is not reliable, at least when occurrences in a period of one year
      or more are evaluated. The use of patient records as a reference of accuracy is
      also unreliable, unless all the health care services available to the people in
      the community are covered.

PMID- 15969455
TI  - The influence of active maternal smoking during pregnancy on birth weights in
      Cyprus.
AB  - Cigarette smoking during pregnancy has been causally associated with an increased
      risk of both intrauterine growth retardation and preterm delivery but most
      strongly with low birth weight. No such study to date had ever dealt with the
      Cypriot population. In interviews with their gynaecologists 65,530 pregnant women
      were asked between January 1990 and August 1996 to answer two questions, whether
      they had been smoking before and whether they had been smoking during pregnancy.
      Data from 59,014 births were considered to have valid birth weight data for this
      investigation. In 81.2% of the cases the mother explicitly declared that she had
      neither smoked before or during pregnancy whereas in 1.4% of the cases the mother
      said that she had smoked both before and during pregnancy and in 1.4% of the
      cases the mother said that she had smoked before but not during pregnancy.
      Finally, in 15.3% of the cases no answer to "smoking question" was given, whereas
      in 0.7% of the cases the answer that was given was deemed as not clear. The
      average birth weight of babies born to women who had stopped smoking was
      insignificantly different than that of those born to never smokers. The average
      birth weight of babies born to women who smoked during pregnancy was lower
      compared to babies born to non smokers' babies by 92 grams, 66 grams, and 109
      grams for all babies, singleton boys and singleton girls respectively. The
      greatest effect to their mean birth weights was observed in babies whose mothers
      did not answer the question on smoking. Their babies had birth weights lower than
      non smokers' babies by 203 grams, 197 grams, and 201 grams for all babies,
      singleton boys and singleton girls respectively.

PMID- 15969456
TI  - Monitoring of trace elements in breast milk sampling and measurement procedures.
AB  - The aims of this study were to test analytical procedures for the determination
      of Cd, Cu, Mn, Pb, Se and Zn in breast milk and to establish optimum sampling
      conditions for monitoring purposes. Two population groups were analysed: (1)
      Seven women from Prague whose breast milk was sampled on days 1,2, 3, 4, 10, 20
      and 30 after delivery; (2) 200 women from four (two industrial and two rural)
      regions whose breast milk was sampled at defined intervals. All samples were
      mineralised in a microwave oven in the mixture of HNO3 + H2O2 and analysed by
      atomic absorption spectrometry. Conditions for the measurement of the elements
      under study (i.e. those for the electrothermal atomisation for Cd, Mn and Pb,
      flame technique for Cu and Zn, and hydride generation technique for Se) were
      optimized. Using optimized parameters the analysis was performed and the
      following conclusion has been made: the concentrations of zinc and manganese
      decreased very sharply over the first days, that of copper slightly increased
      within the first two days and then slightly decreased, that of selenium did not
      change significantly. Partial "stabilisation" was achieved after the second
      decade. No correlation among the elements was found. A significant difference
      between whole and skim milk was only found for selenium (26% rel. higher in whole
      milk). The majority concentrations of cadmium and lead were below the detection
      limit of the method (0.3 microg x l(-1) and 8.2 microg x l(-1), respectively, as
      calculated for the original sample). To provide biological monitoring, the
      maintenance of sampling conditions and especially the time of sampling is
      crucial.

PMID- 15969457
TI  - Resistance of Yersinia enterocolitica, Escherichia coli O157:H7 and natural
      microflora against acidic conditions and freezing-thawing in fresh sausages.
AB  - The resistance of Yersinia enterocolitica O:9, Escherichia coli O157:H7 and
      natural microflora against lactic acid (LA), ascorbic acid (AA), and freezing
      thawing in noninoculated and inoculated fresh sausages was studied. Samples were
      stored at -18 degrees C for 28 days and thawed in microwave (MW), at room
      temperature (RT), in refrigerator (R) and under flowing of tap water (F) on days
      7, 14, 21 and 28. Plate Count Agar (PCA), Sorbitol Mac Conkey agar (SMC) and Mac
      Conkey agar (MC) were used for microbial counts. A maximal reduction of 1.57 log
      in mesophilic aerobes and no significant changes in total and fecal coliform
      levels with respect to the initial counts in natural microflora were observed
      along storage. In inoculated fresh sausages, reductions of 1.37 log on PCA and
      2.17 log on SMC were obtained in E. coli O157:H7 populations as compared to the
      control groups on day 0. Similarly, reductions of 1.69 log on PCA and 2.79 log on
      MC as compared to the initial level were observed in counts of Y. enterocolitica
      inoculated samples. Salmonella Anatum, P. aeruginosa, Y. enterocolitica B1A O:7,8
      8-8,19 and E. coli non O157:H7 strains were recovered from the natural microflora
      by enrichment techniques. Thawing in refrigerator was more frequently related to
      the best reductions of total mesophilic aerobe, E. coli O157:H7 and Y.
      enterocolitica O:9 counts than the other thawing methods. Reductions of microbial
      populations observed in LA treated samples were similar to those observed in AA
      treated samples. Although the acidic and freezing treatments might reduce the
      microbial levels in natural microflora of fresh sausages, they appeared to be
      ineffective in the total elimination of high inocula of pathogens like E. coli
      O157:H7 and Y. enterocolitica O:9.

PMID- 15969458
TI  - Association between trichomoniasis and bacterial vaginosis: examination of 600
      cervicovaginal smears.
AB  - To determine whether there is a relationship between trichomoniasis and bacterial
      vaginosis (BV), cervicovaginal smears obtained from 600 women were stained with
      the Papanicolaou technique and examined cytologically. Thirty-six (6%) of 600
      women were diagnosed as having Trichomonas vaginalis [TV(+)]. Sixteen (44.4%) of
      36 TV(+) cases were observed as having BV [BV(+)]. Thirty-one of 564 TV(-)
      vaginal smears were also positive for BV (5.5%). There was a statistically
      significant correlation between trichomoniasis and bacterial vaginosis (p <
      0.05). It is possible that TV might create an anaerobic environment, thereby
      changing the vaginal flora. This flora becomes a more suitable milieu for growing
      of anaerobic microorganisms. It can be postulated that TV might be the most
      important protozoan that contributes to the overgrowth of BV-related
      microorganisms.

PMID- 15969459
TI  - Persistence of antibodies against tetanus upon revaccination.
AB  - To assess the interval since the last revaccination against tetanus the
      persistence of antibodies was determined using ELISA test in 128 subject. Levels
      of antibodies against tetanus higher than the protective level of 0.1 IU/ml were
      found not only in those revaccinated less than ten years ago, but also in those
      revaccinated more than ten years before. With increasing length of the interval
      since last revaccination the antibody levels against tetanus decreased gradually
      although they remained above the protective level. No basic dependence of that
      trend on gender or age has been found. In the whole series, antibodies against
      tetanus exceeded the protective level for up to 20-25 years post last
      revaccination. This finding together with a favorable epidemiological situation
      as regards the occurrence of tetanus could eventually enable to prolong the
      interval for revaccinating adults in the Czech Republic.

PMID- 15969460
TI  - Diurnal and spatial patterns of Phytoseiidae in the citrus canopy.
AB  - Phytoseiid mites were sampled in a grapefruit orchard at various times of the day
      to study their diurnal and seasonal distributions in the tree canopy. Samples
      were collected on 14, 20 and 28 October 1999 at 2 h intervals from 0600 to 2200
      h. Similar samples were collected in a grapefruit orchard at 3 h intervals from
      0600 to 2100 h on 9 and 16 March and on 17 and 24 August 2000 for phytoseiid
      mites. No differences in numbers of phytoseiid motiles were observed among the
      hours sampled in any of the three months. However, significant differences were
      observed in the number of phytoseiids per leaf based on location within the tree
      (eastern, western sides of the canopy or interior). Interior leaves collected in
      March and August 2000 had higher numbers of phytoseiids than exterior leaves
      taken from either the eastern or western sides of the tree canopy. Phytoseiids
      were more abundant in the March 2000 samples (mean = 1.10 phytoseiids/leaf) than
      in either October 1999 or August 2000 samples (mean = 0.16 and 0.19
      phytoseiids/leaf, respectively). Prevalent phytoseiid species were Typhlodromalus
      peregrinus (Muma) (42.1%) and Iphiseiodes quadripilis (Banks) (50.4%) in October
      1999, Typhlodromalus peregrinus (Muma) (76.2%) in March 2000, and Euseius
      mesembrinus (Dean) (54%) in August 2000.

PMID- 15969461
TI  - In vitro and in vivo inhibition of alpha-amylases of stored-product mite Acarus
      siro.
AB  - The stored-product mites are the most abundant and frequent group of pests living
      on the stored food products in Europe. They endanger public health since they
      produce allergens and transmit mycotoxin-producing fungi. Novel acaricidal
      compounds with inhibitory effects on the digestive enzymes of arthropods are a
      safe alternative to the traditional neurotoxic pesticides used for control of the
      stored-product pests. In this work, we explored the properties of acarbose, the
      low molecular weight inhibitor of alpha-amylases (AI), as a novel acaricide
      candidate for protection of the stored products from infestation by Acarus siro
      (Acari: Acaridae). In vitro analysis revealed that AI blocked efficiently the
      enzymatic activity of digestive amylases of A. siro, and decreased the
      physiological capacity of mite's gut in utilizing a starch component of grain
      flour. In vivo experiments showed that AI suppressed the population growth of A.
      siro. The mites were kept for three weeks on experimental diet enriched by AI in
      concentration range of 0.005 to 0.25%. Population growth of A. siro was
      negatively correlated with the content of AI in the treated diet with a half
      population dose of 0.125%. The suppressive effect of AIs on stored-product mites
      is discussed in the context of their potential application in GMO crops.

PMID- 15969462
TI  - Efficacy of various synthetic pyrethroid-impregnated encasement materials against
      house dust mite under laboratory conditions.
AB  - The acaricidal activity of synthetic pyrethroid and benzyl benzoate against
      Dermatophagoides pteronyssinus was examined in the laboratory, using a specially
      designed test set up. On the basis of median lethal dose (LD50) values, the
      compound found to be most toxic to D. pteronyssinus was benzyl benzoate (LD50 =
      50 mg/m2), followed by permethrin (LD50 = 76.7 mg/m2), deltamethrin (LD50 = 146.7
      mg/m2), esbioallenthrin (LD50 = 186.6 mg/m2) and lamdacyhalothrin (LD50 = 756.6
      mg/m2). Very low toxicity was observed with bifenthrin (LD50 = 5157.8 mg/m2). A
      laboratory control trial was also carried out to compare the acaricidal activity
      (residual effect) of four pyrethroids impregnated on woven and non-woven
      encasement materials against house dust mites during a 4-month period. Of the
      pyrethroids used in this study, esbioallenthrin demonstrated the highest
      acaricidal activity, and of the pyrethroid impregnated materials, the non-woven
      encasement material was more effective than the woven encasement material.

PMID- 15969464
TI  - Ontogeny of tick hemocytes: a comparative analysis of Ixodes ricinus and
      Ornithodoros moubata.
AB  - Hemocytes of two tick species, Ixodes ricinus and Ornithodoros moubata, were
      investigated with the aim to determine their ultrastructural characteristics and
      developmental relationships. Only a limited number of ultrastructural features
      was shown to be unequivocally homological across all hemocyte types. The two
      species, representing distant groups of ticks, differ in the composition of their
      circular cell populations. In I. ricinus, three groups of distinct morphological
      types of hemocytes could be determined according to well-defined ultrastructural
      features: a typical non-phagocytic granular cell with electron-dense granula and
      homogeneous cytoplasm (Gr II), and two different types of phagocytic hemocytes,
      namely plasmatocytes with a low number of granula and phagocytic granolocytes,
      designated as Gr I. In contrast, an additional cell type resembling insect
      spherulocytes was determined in O. moubata. This cell type does not seem to be
      homologous to any I. ricinus hemocyte and may represent a cell type typical of
      soft ticks only. Possible ontogenetic lineages of the hemocytes of both tick
      species were inferred.

PMID- 15969463
TI  - Pathogenicity of Metarhizium anisopliae (Deuteromycetes) and permethrin to Ixodes
      scapularis (Acari: Ixodidae) nymphs.
AB  - Effectiveness of the entomopathogenic fungus Metarhizium anisopliae, for
      controlling nymphal Ixodes scapularis, was tested in laboratory and field trials.
      In the laboratory, M. anisopliae (Metschnikoff) Sorokin strain ESC1 was
      moderately pathogenic, with an LC50 of 10(7) spores/ml and induced 70% mortality
      at 10(9) spores/ml. In a field study, however, 10(9) spores/ml M. anisopliae did
      not effectively control questing I. scapularis nymphs, and significant
      differences were not detected in pre- and post-treatment densities. For nymphs
      collected and returned to the laboratory for observation, mortality was low in
      treatment groups, ranging from 20 to 36%. To assess whether a chemical acaricide
      would synergistically enhance pathogenicity of the fungus, we challenged unfed
      nymphal I. scapularis with combinations of M. anisopliae and permethrin, a
      relatively safe pyrethroid acaricide, in two separate bioassays. Significant
      interactions between M. anisopliae and permethrin were not observed, supporting
      neither synergism nor antagonism.

PMID- 15969465
TI  - Reptile trade and the risk of exotic tick introductions into southern South
      American countries.
AB  - Ticks exotic for the Neotropical region were found on Python regius imported into
      Argentina and Chile. All ticks (7 males and 3 females) were classified as
      Amblyomma latum Koch, 1844 ( = Aponomma latum). Additionally, four lots
      comprising 18 males of the Argentinean tortoise tick, Amblyomma argentinae
      Neumann, 1904, were found on a terrestrial tortoise, Chelonoidis chilensis, and
      on three terrestrial tortoises (probably C. chilensis) imported to Uruguay
      presumably from Argentina). These findings alert us to the risk of expanding the
      distribution of reptile parasites and their diseases into regions previously free
      of these parasites.

PMID- 15969466
TI  - A note on Hyalomma nitidum, its distribution and its hosts.
AB  - The paper summarises the morphological characteristics, the known geographical
      distribution and hosts of Hyalomma nitidum, a tick which has never been properly
      characterised. H. nitidum was first described in Cameroon in 1919, long
      considered as a synonym of Hyalomma truncatum and recognised as a separate and
      valid species only since the early 1970s. H. nitidum occurs from Senegal to the
      Central African Republic in more humid conditions than H. truncatum, roughly to
      the south of the isohyet of 900 mm. Adults are parasitic on various wild and
      domestic ungulates, on which immatures have not been found. Nymphs, identified
      after moulting to adults, have been found on a hare, and tentatively identified
      larvae and nymphs of this species have also been collected on hare as well as on
      a zebra mouse. The tick has been found infected with the virus of Crimean-Congo
      haemorrhagic fever, so far no other disease associations are known.

PMID- 15969467
TI  - Staphylococcus aureus strain designation by agr and cap polymorphism typing and
      delineation of agr diversification by sequence analysis.
AB  - The allelic variations of the regulatory operon agr (groups I-IV) and the cap
      polymorphism (capsular types 5 and 8) were used as a typing scheme for rapid
      strain designation in Staphylococcus aureus. In combining 10 agr subgroups
      resolved by restriction fragment length polymorphism (RFLP) analysis with the two
      cap polymorphisms 12 types could be defined. To assess whether this type
      designation is informative for the population structure of the species S. aureus,
      agr and cap types were determined in clonal lineages defined by pulsed-field gel
      electrophoresis (PFGE) of a collection of 219 isolates. agr groups and cap types
      were both linked to certain clone complexes. However, little correlation was
      found between the two polymorphic loci. By PFGE cluster analysis 11 prevalent and
      52 sporadic clones were defined. Most of the prevalent clones (9/11) could be
      discriminated by agr/cap typing. Thus, this technique allows a first subdivision
      of isolates and an inter-center comparable designation of S. aureus clones
      preceding a more detailed clonal analysis by PFGE or multi-locus sequence typing
      (MLST). To get insight into agr diversification, sequence analysis of the
      variable and conserved part of agr from selected S. aureus clones was performed.
      Strains of agr-I displayed the highest sequence divergence on the nucleotide and
      amino acid level, suggesting an early diversification of this group. When
      analyzing the relationship between the four agr interference groups we could
      show: (i) one intermediate between agr-I and agr-IV alleles; (ii) agr-IV
      sequences seem to bridge the agr-I and -III groups and (iii) two cases of
      horizontal transfer of the variable gene cassette from an agr-I strain to an agr
      II strain. Thus, stepwise evolutionary progression and rare events of
      recombination were evident in the diversification of the agr locus.

PMID- 15969468
TI  - Development of a real-time PCR assay for rapid identification of methicillin
      resistant Staphylococcus aureus from clinical samples.
AB  - A major drawback of mecA PCR to detect methicillin-resistant Staphylococcus
      aureus (MRSA) directly from patient materials is the high frequency of
      methicillin-resistant coagulase-negative staphylococci. Therefore, a reliable
      detection method for MRSA from clinical samples using real-time PCR was
      developed. The PCR assay targeting the integration site (orfX) of the
      staphylococcal cassette chromosome mec (SCCmec) was evaluated in MRSA SCCmec
      reference strains (n = 9), MRSA ST strains (n = 16) and clinical isolates of MRSA
      (n = 124), MSSA (n = 53), methicillin-resistant coagulase-negative staphylococci
      (n = 47), and methicillin-susceptible, coagulase-negative staphylococci (n = 32).
      The diagnostic values of the assay were 98% sensitivity and 100% specificity.
      Furthermore, the PCR detection method was evaluated with 60 swabs from different
      body sites which were incubated overnight in brain-heart infusion. The PCR gave
      positive results for 27 of 29 swabs which were found to contain MRSA by
      conventional methods. The diagnostic values of the PCR assay for these samples
      were 93% sensitivity and 100% specificity. To determine the in vitro sensitivity
      of the assay, swabs were inoculated with serially diluted bacterial suspensions.
      After overnight enrichment the detection limit of the PCR was less than 10
      CFU/swab. This new real-time PCR assay proved to be a fast, sensitive and
      specific tool for MRSA detection in a routine microbiological laboratory.

PMID- 15969469
TI  - Identification of laminin-binding motifs of Yersinia pestis plasminogen activator
      by phage display.
AB  - Yersinia pestis plasminogen activator (Pla), a surface virulence factor
      contributes to the highly invasive nature of the pathogen by binding various
      tissue matrix components. In this study we characterised the laminin-binding
      site(s) of Pla via phage display and alanine-scanning mutagenesis. Previously we
      isolated 18 different heptamer peptide sequences from a phage display library
      with biopanning on laminin, and have shown that two of them with sequences of
      WSLLTPA or YPYIPTL completely inhibited laminin binding of a Pla-expressing
      recombinant Escherichia coli strain. These phages themselves strongly bound
      laminin in an ELISA assay utilising horseradish peroxidase-labelled anti-M 13
      antibody. In the present study, with the application of synthetic peptides, a 55%
      and a 33% inhibition was demonstrated using WSLLTPA and YPYIPTL, respectively.
      Peptide pattern alignment showed two homologous regions for WSLLTPA and one for
      YPYIPTL inside the Pla sequence. Amino acids were changed for alanine in one of
      the WSLLTPA regions and in the YPYIPTL region in order to prove the role of the
      LTP/PTL motifs in laminin binding. Of the four constructed mutants, the triple
      mutant L65A-T66A-L67A in the WSLLTPA region and the double mutant G178A-L179A in
      the YPYIPTL region decreased the laminin binding capacity of the Pla-expressing
      recombinant E. coli by about 50%.

PMID- 15969470
TI  - The detection of salmochelin and yersiniabactin in uropathogenic Escherichia coli
      strains by a novel hydrolysis-fluorescence-detection (HFD) method.
AB  - Escherichia coli strains produce a variety of structurally different siderophores
      of which enterobactin, aerobactin and yersiniabactin have been reported earlier
      to occur in strains of extraintestinal infections. In uropathogenic E. coli
      (UPEC) strains novel siderophores, named salmochelins, have recently been
      identified which contain C-glucosylated 2,3-dihydroxybenzoyl-L-serine (glucosyl
      DHB-serine) residues connected in a linear (mono-, di- , trimeric) or cyclic
      form. We report here on a fast and simple hydrolysis-fluorescence-detection (HFD)
      method, based on identification of C-glucosylated dihydroxybenzoic acid (glucosyl
      DHB). Salmochelin containing culture filtrates were bound to DEAE cellulose spin
      columns, hydrolyzed and the breakdown products were subsequently identified by
      HPLC or thin layer chromatography (TLC). The hydrolysis products can be easily
      detected by their fluorescence, either during HPLC separation connected to a
      fluorescence detector or after TLC on cellulose plates viewed under a UV254 or
      UV365 lamp. While DHB originates from the hydrolysis of enterobactin and
      salmochelin, glucosyl-DHB is only found as a characteristic hydrolysis product of
      salmochelins (S1, S2, S4). The HFD method allows detection of salmochelin in the
      presence of other siderophores, such as enterobactin, aerobactin and
      yersiniabactin. Several clinical UPEC isolates containing the iroN gene cluster
      were analyzed by this procedure, showing that all isolates were glucosyl-DHB
      positive indicating salmochelin production, while a collection of other
      pathogenic E. coli strains (EHEC, EIEC, ETEC, EAggEC and EPEC) were glucosyl-DHB
      negative. In addition, the HFD method allowed the identification of
      yersiniabactin due to a fluorescent salicylate-containing degradation product.

PMID- 15969471
TI  - An Enterobacter cloacae toxin able to generate oxidative stress and to provoke
      dose-dependent lysis of leukocytes.
AB  - We investigated an Enterobacter cloacae strain exhibiting high hemolytic and
      leukotoxic activity. Monomeric and polymeric forms of the toxin showed similar
      effects on blood cells, although the polymer was more active than the monomer.
      Fluorescence microscopy revealed that both forms of the FITC-labeled toxin
      interacted with leukocytes, principally with neutrophils. Prelytic concentrations
      of polymeric and monomeric toxin significantly increased the production of
      reactive oxygen species (ROS) in neutrophils. Conversely, lytic concentrations of
      both toxin forms showed an increase followed by a decrease of ROS due to
      neutrophil damage. Monocytes did not show oxidative stress at all the toxin
      concentrations assayed. The toxin-neutrophil interaction at prelytic
      concentrations of toxin-stimulated ROS production and led to oxidative stress
      with subsequent cell death by apoptosis. However, high concentrations of E.
      cloacae toxin damaged leukocytes, producing lysis before the trigger of
      apoptosis, which suggests that the toxic effect is concentration dependent. The
      inhibition of oxidative stress observed with genistein and chloroquine suggests a
      potential involvement of the tyrosine kinase and nitric oxide synthesis pathways
      in E. cloacae toxin-mediated elevation of ROS.

PMID- 15969472
TI  - Quantitative detection of Salmonella enterica serovar Typhi from blood of
      suspected typhoid fever patients by real-time PCR.
AB  - We quantified the gene copies from Salmonella enterica serovar Typhi (S. Typhi)
      in the blood of patients suspected of having typhoid fever by using TaqMan-based
      real-time PCR (TaqMan assay) to target the S. Typhi flagellin gene in genomic
      DNAs isolated from blood samples. Of 55 blood samples taken from suspected
      typhoid fever patients, eight blood samples with a positive blood culture had S.
      Typhi loads ranging from 1.01 x 10(3) to 4.35 x 10(4) copies/ml blood, and from
      47 blood samples with negative blood culture, there were 40 (85.1%) TaqMan assay
      positive samples with loads ranging from 3.9 to 9.9 x 10(2) copies/ml blood. In
      the present study, the TaqMan assay detected more than 10(3) copies/ml blood of
      S. Typhi in all of the blood culture-positive samples, whereas less than 10(3)
      copies/ml blood of S. Typhi were detected in the blood culture-negative samples.
      Our findings suggest that a TaqMan assay may be useful for assessing S. Typhi
      loads, especially in cases of suspected typhoid fever with negative results from
      the standard blood culture test.

PMID- 15969473
TI  - Polymorphism of Candida albicans is a major factor in the interaction with human
      dendritic cells.
AB  - Morphological plasticity of Candida albicans is a major virulence factor. Using
      pH-dependent dimorphism we show, that human dendritic cells (DC) recognize
      filamentous forms and blastoconidia of a virulent C. albicans isolate (strain
      SC5314). Heat inactivated and viable blastoconidia are rapidly phagocytosed by
      human DC. However, viable yeast cells start to filament inside the DC at later
      stages of infection, leading to penetration and loss of cellular integrity. The
      cytokine burst of human DC induced upon contact with Candida is dominated by the
      granulocyte-activating, chemotactic factor IL-8 and the proinflammatory mediator
      TNF-alpha. Blastoconidia induce markedly lower cytokine levels than filamentous
      forms. Whereas IL-8 secretion is mainly cell mass dependent, release of TNF
      alpha, a major proinflammatory cytokine, is clearly dependent on the morphology
      of Candida.

PMID- 15969474
TI  - Preparation of fatty acid methyl esters for gas-chromatographic analysis of
      marine lipids: insight studies.
AB  - Assays for fatty acid composition in biological materials are commonly carried
      out by gas chromatography, after conversion of the lipid material into the
      corresponding methyl esters (FAME) via suitable derivatization reactions.
      Quantitative derivatization depends on the type of catalyst and processing
      conditions employed, as well as the solubility of said sample in the reaction
      medium. Most literature pertinent to derivatization has focused on differential
      comparison between alternative methods; although useful to find out the best
      method for a particular sample, additional studies on factors that may affect
      each step of FAME preparation are urged. In this work, the influence of various
      parameters in each step of derivatization reactions was studied, using both cod
      liver oil and microalgal biomass as model systems. The accuracies of said
      methodologies were tested via comparison with the AOCS standard method, whereas
      their reproducibility was assessed by analysis of variance of (replicated) data.
      Alkaline catalysts generated lower levels of long-chain unsaturated FAME than
      acidic ones. Among these, acetyl chloride and BF(3) were statistically equivalent
      to each other. The standard method, which involves alkaline treatment of samples
      before acidic methylation with BF(3), provided equivalent results when compared
      with acidic methylation with BF(3) alone. Polarity of the reaction medium was
      found to be of the utmost importance in the process: intermediate values of
      polarity [e.g., obtained by a 1:1 (v/v) mixture of methanol with diethyl ether or
      toluene] provided amounts of extracted polyunsaturated fatty acids statistically
      higher than those obtained via the standard method.

PMID- 15969475
TI  - Multi-element analysis of South African wines by ICP-MS and their classification
      according to geographical origin.
AB  - Wines from three important wine-producing regions, Stellenbosch, Robertson, and
      Swartland, in the Western Cape Province of South Africa, were analyzed by ICP-MS
      and the elemental composition used in multivariate statistical analysis to
      classify the wines according to geographical origin. The method is based on the
      assumption that the provenance soil is an important contributor to the trace
      element composition of a wine. A total of 40 elements were determined in 40
      wines. Of these, 20 elements: Li, B, Mg, Al, Si, Cl, Sc, Mn, Ni, Ga, Se, Rb, Sr,
      Nb, Cs, Ba, La, W, Tl, and U showed differences in their means across the three
      areas. In a stepwise discriminant analysis procedure, functions based on linear
      combinations of the log-transformed element concentrations of Al, Mn, Rb, Ba, W,
      and Tl were generated to correctly classify wines from each region. In an
      alternative approach, a pairwise discriminant analysis procedure, not previously
      used in wine provenance studies, was tested. In this procedure, the
      classification was done in three steps, with each step classifying a wine as
      coming from a certain region or not. The combination of elements characterizing
      wines from a particular region was different in each region. The discriminant
      functions were based on the following elements: Al, Mn, Rb, Ba, and W for
      Stellenbosch; Se, Rb, Cs, and Tl for Robertson; and Al, Mn, Rb, Sr, Ba, and Tl
      for Swartland. After this procedure, the classification of the wines into one of
      the groups was 100% successful.

PMID- 15969476
TI  - Chemometric characterization of the cypriot spirit "zivania".
AB  - In 42 alcoholic beverages produced in Cyprus and other countries, 26 chemical and
      physical-chemical variables were determined by HPLC and GC chromatography, (1)H
      NMR and ICP spectroscopy, and other techniques. Data were processed using
      multivariate chemometric techniques, involving principal component analysis,
      cluster analysis, regularized discriminant analysis, and classification and
      regression trees. Zivania can be differentiated from beverages from other
      countries. Using 2- and 3-methyl-butanol, 2-methyl-propanol, furfural, methanol,
      and the alcoholic grade and the chemical shift of -CH(3) in (1)H NMR spectra as
      features, a nearly correct classification for zivania was achieved. The reasons
      for diversions are given.

PMID- 15969477
TI  - Enzyme-assisted extraction of moniliformin from extruded corn grits.
AB  - Water has been known to be the ideal solvent for moniliformin but is not suitable
      to extract this toxin from cooked matrices due to instant swelling upon addition
      of the solvent. In this study, an improved method to extract moniliformin from
      extruded corn grits using alpha-amylase was developed. In an effort to optimize
      the method, the efficacy of using a protease was also studied. Treatment with
      alpha-amylase resulted in a clear solution with decreased suspended solid content
      as measured by transmittance (%T), which improved from 0 to 96% in 10 min. The
      detected level of moniliformin from extruded corn grits was increased to 4.02
      mug/g when extracted with 1% tetrabutylammonium hydrogen sulfate following alpha
      amylase treatment compared to 2.56 microg/g when it was extracted with 90%
      acetonitrile without enzyme treatment. The average recovery of moniliformin from
      extruded corn grits was 96% when alpha-amylase was used in the extraction
      procedure. Overall, the amounts of moniliformin detected in extruded corn grits
      increased significantly by using enzyme hydrolysis. Chromatographic separation
      was also benefited by lesser interference and improved peaks.

PMID- 15969478
TI  - Pesticide extraction efficiency of two solid phase disk types after shipping.
AB  - An interlaboratory study was conducted to compare pesticide recovery from Empore
      C(18) and Speedisks C(18)XF solid phase extraction disks after shipping. Four
      pesticides were used for the comparison of the two disk extraction materials:
      atrazine, diazinon, metolachlor, and tebuconazole. These pesticides were chosen
      to provide a range of physiochemical properties. Water samples were extracted
      onto the disk types and shipped to a cooperating laboratory for elution and
      analysis. The mean recoveries from Empore disks were atrazine, 95%; diazinon,
      91%; metolachlor, 92%; and tebuconazole, 83%. The recoveries from Speedisks
      C(18)XF were atrazine, 89%; diazinon, 87%; metolachlor, 86%; and tebuconazole,
      79%. Means for each of the pesticides using the different disk types were not
      statistically different (alpha = 0.05), but results were more variable when using
      Speedisks C(18)XF as compared to Empore disks. Reasons for the increased
      variability are discussed, but overall results indicate that Speedisks C(18)XF
      could be used as an alternative to Empore disks. Speedisks C(18)XF are enclosed
      in a plastic housing, so they can be used more easily in remote sampling sites
      without the possibility of glassware breakage, no prefiltration of samples is
      needed, and there are realignment problems that can be associated with the Empore
      disks.

PMID- 15969479
TI  - Determination of some heavy metals and selenium in Sicilian and Calabrian citrus
      essential oils using derivative stripping chronopotentiometry.
AB  - This paper aims to bring some novelty about the concentration of some heavy
      metals and selenium in biological citrus essential oils (CEO) produced in Sicily
      and Calabria in different crop years. Derivative stripping chronopotentiometry
      has been used as an accurate, sensitive, and rapid technique for the
      determination of Cd, Cu, Mn, Ni, Pb, Zn, and Se in hydrochloric acid extracts of
      CEO; in the optimized electrochemical conditions, detection limits of <1 microg
      kg(-1) were obtained for all of the studied metals. In particular, the
      concentrations of metals were determined in biological bergamot essential oils
      produced in Calabria in 1999 and 2000 and in biological CEO produced in Sicily in
      2003 and 2004. The obtained results provided evidence that Mn was the most
      abundant metal in all of the studied CEO followed by Zn, Ni, Cu, Pb, and Se; Cd
      concentrations were always lower than the limit of detection (0.6 microg kg(-1)).

PMID- 15969480
TI  - Structural investigation of edible zein films/coatings and directly determining
      their thickness by FT-Raman spectroscopy.
AB  - Near-infrared Fourier transform Raman (FT-Raman) spectroscopy was employed to
      study the molecular structure of edible zein films/coatings, which were
      fabricated directly from zein protein. The secondary structure of zein protein
      was mainly in alpha-helix and remained unaltered during film formation as
      evidenced by the vibrational modes of amide I at 1656 cm(-1) and amide III at
      1274 cm(-1). Raman results indicated that hydrophobic interaction played an
      important role in the formation of zein film and disulfide bonding might be
      responsible for the structural stability of zein protein during film formation.
      To enhance its antimicrobial property, an antimicrobial zein film was
      manufactured by incorporating zein protein with benzoic acid whose structure was
      then characterized by FT-Raman. It showed that physical entrapment or hydrophobic
      interaction was crucial to the incorporation of benzoic acid with zein protein,
      and the secondary structure of the antimicrobial film was still maintained in
      alpha-helical form. In addition, FT-Raman exhibits its preference in directly
      determining the thickness of zein films/coatings. By correlating the Raman
      intensity ratio of nu(1003) to nu(84) (I(1003/84)) versus the thickness of zein
      film, a linear relationship with high coefficient (R(2) = 0.9927) was obtained,
      which was then used pragmatically to determine the thickness of zein coatings on
      apple. It showed that the FT-Raman result (thickness = 0.27 +/- 0.01 mm) was
      consistent with that of classical micrometric measurement (thickness = 0.28 +/-
      0.02 mm). Consequently, FT-Raman provides a direct, simple, and reagent-free
      method to characterize the structure and the thickness of zein films/coatings.

PMID- 15969481
TI  - Molecular and immunochemical characteristics of monoclonal and recombinant
      antibodies selective for the triazine herbicide simetryn and application to
      environmental analysis.
AB  - A monoclonal antibody (mab) selective for the thiomethyl-s-triazine herbicide
      simetryn was obtained and characterized in enzyme-linked immunosorbent assay
      (ELISA). An IC(50) value for simetryn was 8.5 ng/mL, and the detection range
      extended from 1.1 to 70 ng/mL in ELISA. The cDNAs encoding variable heavy chain
      (VH) and variable light chain (VL) of the mab were cloned to produce various
      recombinant antibodies. Single-chain variable fragment (scFv) antibodies derived
      from the mab were characterized in ELISA and showed similar reactivities and
      specificities to the parent mab. A urea denaturation test revealed that the scFv
      antibodies bound to simetryn were more stable than those in the absence of
      antigen. A sandwich ELISA based on VH and VL fragments of the mab was
      successfully developed and showed similar sensitivity to those based on the mab
      and scFv antibodies in ELISA. In the recovery experiments using spiked
      environmental samples, the results obtained in ELISA based on the mab were
      favorably correlated with those by HPLC.

PMID- 15969482
TI  - Determination of pesticides and PCBs in virgin olive oil by multicolumn solid
      phase extraction cleanup followed by GC-NPD/ECD and confirmation by ion-trap GC
      MS.
AB  - A multicolumn solid-phase extraction cleanup for the determination of
      organophosphorus (OP) and organochlorine (OC) pesticides plus PCB congeners in
      virgin olive oil is presented. The method involves dissolution of the olive oil
      in hexane, followed by a cleanup system using a diatomaceous earth column
      (Extrelut-QE) with reversed (C(18)) and normal (alumina) phase SPE columns.
      Determination of OPs was by GC-NPD, while the OCs and PCBs were analyzed using GC
      ECD. Recovery assays for OPs varied from 81.7% to 105.3%, for OCs ranged between
      74.3% and 99.4%, while for PCBs were from 60.1% to 119.2%. Quantitation limits
      ranged from 10 to 25 microg/kg olive oil for OPs, and from 1 to 6 microg/kg olive
      oil for OCs and PCBs. In the case of positive samples, the confirmation of
      pesticide identity was performed by ion-trap GC-MS/MS. The applicability of the
      method was assayed with 19 virgin olive oil samples collected from different
      olive mills of Aragon (Spain). Only one OP pesticide (acephate) was detected in
      one sample at a concentration of 10 microg/kg. Organochlorine pesticides were
      found in 5-47% of samples at very low levels ranging from 1.5 to 5.2 microg/kg.
      PCBs were found in 20-90% of samples, showing concentrations between 2.3 and 17.3
      microg/kg.

PMID- 15969483
TI  - Disposable biosensor test for organophosphate and carbamate insecticides in milk.
AB  - A highly sensitive and rapid biosensor test based on disposable screen-printed
      thick-film electrodes was developed, which is suitable for monitoring
      organophosphate and carbamate residues in foods of animal origin with increased
      fat contents such as milk. The wild-type enzyme was combined with three
      engineered variants of Nippostrongylus brasiliensis acetylcholinesterase
      (NbAChE), to obtain enhanced sensitivity. The sample pretreatment could be
      reduced to a minimum. There was no extraction or fat removal necessary. With the
      biosensor test paraoxon concentrations down to 1 microg/L could be detected in
      milk. The detection limit for carbaryl was 20 microg/L. Recovery rates for
      paraoxon and carbaryl in milk samples lay between 89 and 107%. Ten milk samples
      from local markets were tested both with the biosensor test and with standard
      chromatographic multiresidue methods. Two milk samples caused AChE inhibition
      rates of >50%. Accordingly, 4 microg/L tebufenpyrad, 4 microg/L tetraconazole,
      and 2 microg/L bifenthrin were detected in one of these milk samples. The other
      milk sample contained 2 microg/L tebufenpyrad.

PMID- 15969484
TI  - Quantitation of N2-[1-(1-carboxy)ethyl]folic acid, a nonenzymatic glycation
      product of folic acid, in fortified foods and model cookies by a Stable isotope
      dilution assay.
AB  - A stable isotope dilution assay (SIDA) for the quantitation of N(2)-[1
      (carboxy)ethyl]folic acid (CEF) has been developed by using [(2)H(4)]CEF as the
      internal standard. After sample cleanup by anion exchange chromatography, the
      three-dimensional specifity of liquid chromatography-tandem mass spectrometry
      enabled unequivocal determination of the nonenzymatic glycation product of folic
      acid (FA). When CEF was added to cornstarch, the detection limit for CEF was
      found to be 0.4 microg/100 g, and a recovery of 98.5% was determined. In analyses
      of cookies, the intra-assay coefficient of variation was 8.0% (n = 5).
      Application of the SIDA to commercial cookies produced from wheat flour fortified
      with FA revealed CEF contents of up to 7.1 microg/100 g, which accounted for
      approximately 10-20% of the cookies' FA content. In baby foods, multivitamin
      juices, and multivitamin sweets, however, CEF was not detectable. Further studies
      on CEF formation during baking of cookies made from fortified flour and different
      carbohydrates revealed that fructose was most effective in generating CEF
      followed by glucose, lactose, and sucrose with 12.5, 3.9, 2.5, and 2.5 microg/100
      g of dry mass, respectively. During baking, approximately 50% of FA was retained
      for both monosaccharides fructose and glucose, and 77% as well as 85% of its
      initial content was retained for the disaccharides lactose and sucrose,
      respectively. Of the degraded amount of FA, CEF comprised 28% for fructose as
      well as 18, 12, and 8% for sucrose, lactose, and glucose, respectively.
      Therefore, CEF can be considered an important degradation product of FA in baked
      foods made from fructose. To retain a maximum amount of FA, products should
      rather be baked with sucrose than with reducing carbohydrates.

PMID- 15969485
TI  - Natural abundance 2H-ERETIC-NMR authentication of the origin of methyl
      salicylate.
AB  - Methyl salicylate is a compound currently used in the creation of many flavors.
      It can be obtained by synthesis or from two natural sources: essential oil of
      wintergreen and essential oil of sweet birch bark. Deuterium site-specific
      natural isotope abundance (A(i)) determination by NMR spectroscopy with the
      method of reference ERETIC ((2)H-ERETIC-NMR) has been applied to this compound.
      A(i) measurements have been performed on 19 samples of methyl salicylate from
      different origins, natural/synthetic and commercial/extracted. This study
      demonstrates that appropriate treatment performed on the data allows
      discrimination between synthetic and natural samples. Moreover, the
      representation of intramolecular ratios R(6/5) as a function of R(3/2)
      distinguishes between synthetics, wintergreen oils, and sweet birch bark oils.

PMID- 15969486
TI  - Detection of exogenous citric acid in fruit juices by stable isotope ratio
      analysis.
AB  - A new method has been developed for measuring the D/H ratio of the
      nonexchangeable sites of citric acid by isotope ratio mass spectrometry (IRMS).
      Pure citric acid is transformed into its calcium salt and subsequently analyzed
      by pyrolysis-IRMS. The citric acid isolated from authentic fruit juices (citrus,
      pineapple, and red fruits) systematically shows higher D/H values than its
      nonfruit counterpart produced by fermentation of various sugar sources. The
      discrimination obtained with this simplified method is similar to that obtained
      previously by applying site specific isotopic fractionation-nuclear magnetic
      resonance (SNIF-NMR) to an ester derivative of citric acid. The combination of
      carbon 13 and deuterium measurements of extracted citric acid is proposed as a
      routine method for an optimum detection of exogenous citric acid in all kinds of
      fruit juices.

PMID- 15969487
TI  - Phenylacetaldehyde O-methyloxime: a volatile compound produced by grapefruit
      leaves infected with the citrus canker pathogen, Xanthomonas axonopodis pv.
      citri.
AB  - An aldehyde oxime O-methyl ether, phenylacetaldehyde O-methyloxime, was detected
      using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry
      (GC-MS) in the headspace above grapefruit leaves infected with Xanthomonas
      axonopodis pv. citri, the causal agent of citrus bacterial canker disease (CBCD).
      This disease is a major phytosanitary concern, and an eradication campaign
      against it is currently underway in Florida. Phenylacetaldehyde O-methyloxime has
      been reported to be produced by other plants and fragrant flowers, but it was not
      observed in the headspace above uninfected grapefruit leaves, the pathogenic
      bacterium X. axonopodis pv. citri itself, or grapefruit leaves infected with
      another closely related bacterial pathogen, X. axonopodis pv. citrumelo, which
      causes citrus bacterial spot, a disease of no phytosanitary significance. It was
      also not detected from CBCD infected fruits, including orange, lemon, grapefruit,
      and lime. We conclude that phenylacetaldehyde O-methyloxime may potentially be
      used to identify CBCD infestations. However, more intensive studies will be
      required to fully evaluate the potential of phenylacetaldehyde O-methyloxime as a
      diagnostic compound for CBCD. Using SPME and GC-MS to measure phenylacetaldehyde
      O-methyloxime may provide an easy and feasible tool to complement current methods
      used to detect X. axonopodis pv. citri in environmental samples.

PMID- 15969488
TI  - Metallomics approach to trace element analysis in ustilago maydis using cellular
      fractionation, atomic absorption spectrometry, and size exclusion chromatography
      with ICP-MS detection.
AB  - Huitlacoche is the ethnic name of the young fruiting bodies of Ustilago maydis, a
      common parasite of maize. In Mexico and other Latin American countries, this
      fungus has been traditionally appreciated as a local delicacy. In this work a
      metallomics approach was used with the determination of eight elements in
      huitlacoche by electrothermal atomic absorption spectrometry as one facet of this
      approach. The results obtained indicated relatively lower concentrations of
      commonly analyzed metals, as referred to the data reported for other mushroom
      types. This effect was ascribed to different accessibilities of elements,
      depending on fungus substrate (lower from plant than from soil). Subcellular
      fractionation was accomplished by centrifugation of cell homogenates suspended in
      Tris-HCl buffer. Recoveries of the fractionation procedure were in the range of
      71-103%. For six elements (Cr, Cu, Fe, Mn, Ni, and Pb), the mean relative
      contributions in cytosol, cell walls, and mixed membrane fraction were 50.7,
      48.2, and 1.1% respectively. To attain the molecular weight distribution of
      compounds containing target elements as an additional aspect of the metallomics
      approach, the fungus extract (1% sodium dodecyl sulfate in Tris-HCl, 30 mmol L(
      )(1), pH 7.0) was analyzed by size exclusion chromatography with UV and ICP-MS
      detection. With spectrophotometric detection (280 nm), the elution of high
      molecular weight compounds was observed in the form of one peak (MW > 10 kDa),
      and several lower peaks appeared at higher retention times (MW < 10 kDa). On ICP
      MS chromatograms, a coelution of (59)Co, (63)Cu, (57)Fe, (202)Hg, (60)Ni, and
      (80)Se with the first peak on the UV chromatogram was clearly observed,
      indicating that a fraction of each element incorporated with high molecular
      weight compounds (12.7, 19.8, 33.7, 100, 19.4, and 45.8%, respectively, based on
      the peak area measurements). From a comparison of (80)Se and (33)S chromatograms
      (for sulfur analysis, the extract was obtained in the absence of SDS), both
      elements coeluted with the first UV peak, but their lower molecular weight
      compounds were apparently different. These findings may contribute to a better
      understanding of the accumulation of elements in mushrooms.

PMID- 15969489
TI  - Determination of carotenoids in spear shrimp shells (Parapenaeopsis hardwickii)
      by liquid chromatography.
AB  - The objectives of this study were to develop a high-performance liquid
      chromatography method for analysis of carotenoids in spear shrimp shells
      (Parapenaeopsis hardwickii) and to compare the extraction efficiency of
      carotenoids by supercritical carbon dioxide (SCD) and solvents. Results showed
      that the most appropriate HPLC method was accomplished by employing a Cosmosil
      5C18-AR-II column and a mobile phase of methanol-dichloromethane-acetonitrile
      (90:5:5, v/v/v) (A) and water (100%) (B) with the following gradient elution: 92%
      A and 8% B in the beginning, decreased to 4% B in 9.5 min, 1% B in 26 min, 0% B
      in 35 min, maintained for 25 min, and returned to 92% A and 8% B in 61 min. All
      trans-astaxanthin and its two cis isomers, as well as five astaxanthin monoesters
      and 11 diesters were resolved within 60 min with a flow rate at 2 mL/min and
      detection at 480 nm. Astaxanthin diesters were found to contain 12 fatty acids,
      of which palmitic acid and stearic acid constituted a large portion, whereas
      astaxanthin monoesters were found to contain 10 fatty acids with arachidonic acid
      dominating. Solvent extraction could generate a higher content of trans
      astaxanthin and astaxanthin esters, while SCD extraction could produce greater
      levels of 9-cis-astaxanthin and 13-cis-astaxanthin.

PMID- 15969490
TI  - Anti-inflammatory inhibition of endothelial cell adhesion molecule expression by
      flavone derivatives.
AB  - Endothelial expression of cell adhesion molecules (CAM) including VCAM-1, E
      selectin, and PECAM-1 plays a leading role in atherosclerosis. Phenolic flavones
      have been shown to have an anti-inflammatory property. This study examines
      whether 3',4'-dimethoxy-7-hydroxyflavone (methoxyflavone) and 2',3',7
      trihydroxyflavone (hydroxyflavone) inhibited monocyte adhesion to TNF-alpha
      activated endothelium via reduction of CAM expression in human umbilical vein
      endothelial cells (HUVEC). In stimulated HUVEC the expression of VCAM-1 and E
      selectin was enhanced with increasing mRNA levels. Methoxyflavone markedly
      interfered with the THP-1 monocyte adhesion to TNF-alpha-stimulated HUVEC. At
      concentrations of > or =25 microM, methoxyflavone blocked the induction of VCAM-1
      but not that of E-selectin on the activated HUVEC. Immunocytochemical staining
      showed that methoxyflavone modestly inhibited PECAM-1 expression induced by TNF
      alpha. In contrast, hydroxyflavone minimally inhibited TNF-alpha-stimulated E
      selectin expression without affecting VCAM-1 level. The inhibitory effect of
      methoxyflavone on THP-1 adhesion to HUVEC appears to be greater than that of
      hydroxyflavone, most likely due to a greater inhibition of CAM expression. Thus,
      some flavone derivatives containing methoxy groups may have therapeutic potential
      attenuating inflammatory response-related atherosclerosis.

PMID- 15969491
TI  - Distribution of furanocoumarins in grapefruit juice fractions.
AB  - The reported effects of grapefruit (Citrus paradisi Macf.) juice on oral
      bioavailability of certain prescription drugs have led to the discovery of the
      inhibition by compounds in grapefruit of cytochrome P450 3A4 (CYP3A4) in the
      intestinal wall and liver. Recent evidence indicates that furanocoumarins related
      to bergamottin [5-[(3',7'-dimethyl-2',6'-octadienyl)oxy]psoralen] are primarily
      responsible for the grapefruit effect, yet the exact mechanisms and roles that
      specific compounds play in this effect are still uncertain. In the current
      experiments freshly extracted grapefruit juice was separated into four fractions,
      consisting of raw finished juice (approximately 5% fine pulp), centrifugal
      retentate (approximately 35% fine pulp), centrifuged supernatant (<1% pulp), and
      coarse finisher pulp. The relative concentrations of furanocoumarins in each of
      these grapefruit juice fractions were measured by HPLC-MS. These measurements
      showed that the centrifugal retentate had the highest furanocoumarin content,
      containing 892 ppm of bergamottin, 628 ppm of 6',7'-dihydroxybergamottin, 116 ppm
      of 6',7'-epoxybergamottin, 105 ppm of 7-geranyloxycoumarin, and approximately 467
      ppm of furanocoumarin dimers. These high furanocoumarin concentrations make this
      fraction a useful starting material for preparative-scale isolations of these
      compounds. MS analysis of this furanocoumarin-enriched fraction provided evidence
      of additional furanocoumarins in grapefruit juice that remain to be fully
      characterized and evaluated for their roles in the grapefruit-drug interactions.

PMID- 15969492
TI  - Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3
      carbinol, a major indole metabolite present in cruciferous vegetables.
AB  - A variety of studies have suggested a cancer protective role of cruciferous
      vegetables. In the present study, we investigated the effect of indole-3-carbinol
      (I3C), a major indole metabolite in cruciferous vegetables, on cell proliferation
      and in vitro markers of angiogenesis in phorbol myristate acetate (PMA)
      stimulated endothelial EA hy926 cells. The results showed that I3C inhibited the
      growth of EA hy926 cells in a concentration-dependent manner. The capillary-like
      tube formation by PMA-activated endothelial cells was significantly suppressed by
      I3C, and such inhibition was associated with decreased vascular endothelial
      growth factor (VEGF) and increased interleukin-8 (IL-8) secretion, but not with
      the expression of VEGF receptor-2 protein. Additionally, gelatin zymography
      analysis indicated that I3C suppressed activities of matrix metalloproteinases-2
      (MMP-2) and MMP-9 stimulated by PMA. These results suggest that the dietary I3C
      may be useful in the treatment of human cancers and angiogenic diseases.

PMID- 15969494
TI  - alpha-Naphthoflavone, a potent antiplatelet flavonoid, is mediated through
      inhibition of phospholipase C activity and stimulation of cyclic GMP formation.
AB  - The aim of this study was to systematically examine the inhibitory mechanisms of
      the flavonoid alpha-naphthoflavone (alpha-NF) in platelet activation. In this
      study, alpha-NF concentration dependently (5-20 microM) inhibited platelet
      aggregation stimulated by agonists. alpha-NF (5 and 10 microM) inhibited
      intracellular Ca(2+) mobilization, phosphoinositide breakdown, and thromboxane
      A(2) formation stimulated by collagen (1 microg/mL) in human platelets. In
      addition, alpha-NF (5 and 10 microM) markedly increased levels of cyclic GMP and
      cyclic GMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser(157)
      phosphorylation. Rapid phosphorylation of a platelet protein of Mr 47,000 (P47),
      a marker of protein kinase C activation, was triggered by phorbol-12,13
      dibutyrate (60 nM). This phosphorylation was markedly inhibited by alpha-NF (5
      and 10 microM). However, alpha-NF (5 and 10 microM) did not reduce the electron
      spin resonance (ESR) signal intensity of hydroxyl radicals in collagen (1
      microg/mL)-activated platelets. These results indicate that the antiplatelet
      activity of alpha-NF may be involved in the following pathways. (1) alpha-NF may
      inhibit the activation of phospholipase C, followed by inhibition of
      phosphoinositide breakdown, protein kinase C activation, and thromboxane A(2)
      formation, thereby leading to inhibition of intracellular Ca(2+) mobilization.
      (2) alpha-NF also activated the formation of cyclic GMP, resulting in inhibition
      of platelet aggregation. These results strongly indicate that alpha-NF appears to
      represent a novel and potent antiplatelet agent for treatment of arterial
      thromboembolism.

PMID- 15969493
TI  - Bioavailability and antioxidant effects of orange juice components in humans.
AB  - Seven healthy females and six males consumed daily 256 mg of vitamin C, 271 mg of
      flavanones (mainly as glycosides), 6 mg of carotenoids (mainly xanthophylls and
      cryptoxanthins), and 0.16 mg of folate by incorporation of daily three times 236
      mL of not from concentrate orange juice (OJ) into their habitual diet. At the end
      of 3 weeks, mean vitamin C, folate, carotenoid, and flavanone plasma
      concentrations increased significantly relative to baseline by 59% (p < 0.001),
      46% (p = 0.018), and 22% (p < 0.001), and 8-fold (p = 0.045), respectively.
      Flavanones were excreted in urine 9-fold more at the end of the intervention (p =
      0.01) but returned to baseline 2 days after study completion. After the 3 week
      intervention, plasma concentrations of vitamins A and E did not change. 8
      Hydroxydeoxyguanosine in white blood cells declined by 16% (p = 0.38; n = 11),
      and in individuals with high baseline concentrations by 29% (p = 0.36; n = 7),
      respectively. Low-density lipoprotein (LDL)-/high-density lipoprotein (HDL)
      cholesterol ratios decreased but cholesterol (HDL, LDL, total) and thiobarbituric
      acid reactive substance plasma concentrations did not change significantly. We
      conclude from this pilot study that OJ is an excellent food source to enhance
      circulating concentrations of valuable hydrophilic as well as lipophilic
      phytochemicals.

PMID- 15969495
TI  - Naturally occurring antifungal agents against Zygosaccharomyces bailii and their
      synergism.
AB  - Polygodial was found to exhibit a fungicidal activity against a food spoilage
      yeast, Zygosaccharomyces bailii, with the minimum fungicidal concentration (MFC)
      of 50 microg/mL (0.17 mM). The time-kill curve study showed that polygodial was
      fungicidal at any growth stage. The primary action of polygodial comes from its
      ability to disrupt the native membrane-associated function of integral proteins
      as nonionic surface active agents (surfactants) followed by a decrease in plasma
      membrane fluidity. The fungicidal activity of polygodial was increased 128-fold
      in combination with a sublethal amount (equivalent of 1/2 MFC) of anethole and
      vice versa relative to the fungicidal activity of anethole. The fungicidal
      activity of sorbic acid was enhanced 512-fold in combination with 1/2 MFC of
      polygodial. Conversely, the fungicidal activity of polygodial was enhanced 128
      fold in combination with 1/2 MFC of sorbic acid.

PMID- 15969496
TI  - Influence of disaccharide structure on prebiotic selectivity in vitro.
AB  - To obtain structure-function information of a range of carbohydrates, which are
      available only in very small quantities, an in vitro fermentation method using 7
      mg of carbohydrate, 0.7 mL of basal medium, and 1% (w/v) of fecal bacteria was
      validated against a pH-controlled batch culture with 150 mL of basal medium and
      1.5 g of test carbohydrate. This method was used to determine the influence of
      different glycosidic linkages and monosaccharide compositions of disaccharides on
      the selectivity of microbial fermentation. A prebiotic index (PI) was calculated
      for each disaccharide. Generally, disaccharides with linkages of 1-2, 1-4, and 1
      6 generated a high PI score, with kojibiose and sophorose showing the greatest
      values (21.62 and 18.63, respectively). Apart from 6alpha-mannobiose, mannose
      containing disaccharides gave a low PI due to low numbers of bifidobacteria and
      lactobacilli and an increase in bacteroides. The structure-function information
      obtained in this study may lead to a predictive understanding of how specific
      structures are fermented by the human gut microflora.

PMID- 15969497
TI  - Diterpenes from Salvia broussonetii transformed roots and their insecticidal
      activity.
AB  - The new diterpenes brussonol (1) and iguestol (6alpha,11-dihydroxy-12-methoxy
      abieta-8,11,13-triene) (2) with an icetexane and a dehydroabietane skeleton,
      respectively, have been isolated from hairy root cultures of Salvia broussonetii.
      Other previously known diterpenes, 7-oxodehydroabietane, 11-hydroxy-12
      methoxyabietatriene, taxodione, inuroyleanol, ferruginol, deoxocarnosol 12-methyl
      ether, cryptojaponol, pisiferal, sugiol, isomanool, 14-deoxycoleon U, 6alpha
      hydroxydemethylcryptojaponol, demethylsalvicanol, and demethylcryptojaponol, were
      also obtained from these roots. The insect antifeedant and toxic effects of
      several of these compounds were investigated against the insect pests Spodoptera
      littoralis and Leptinotarsa decemlineata. Additionally, their comparative
      cytotoxic effects were tested on insect Sf9 and mammalian CHO cells.
      Demethylsalvicanol (4) was a moderate antifeedant to L. decemlineata, whereas
      brussonol (1) was inactive. 14-Deoxycoleon U (15) was the strongest antifeedant,
      whereas demethylcryptojaponol (11) was toxic to this insect. None of these
      compounds had antifeedant or negative effects on S. littoralis ingestion or
      weight gains after oral administration. Demethylcryptojaponol (11) was cytotoxic
      to mammalian CHO and insect Sf9 cell lines, followed by the icetexane derivative
      brussonol (1), with moderate cytotoxicity in both cases. The remainder of the
      test compounds showed a strong selective cytotoxicty to insect Sf9 cells, with
      demethylsalvicanol (4) being the most active.

PMID- 15969498
TI  - ACE inhibitory activity in enzymatic hydrolysates of insect protein.
AB  - In this paper, ACE inhibitory activity in insect protein hydrolyzed by various
      enzymes (gastrointestinal proteases, alcalase, and thermolysin) is reported for
      the first time. Four insects of different insect orders were tested: Spodoptera
      littoralis (Lepidoptera), Bombyx mori (Lepidoptera), Schistocerca gregaria
      (Orthoptera), and Bombus terrestris (Hymenoptera). ACE inhibitory activity was
      measured by two different methods: a spectrophotometric method using FAPGG (2
      furanacryloyl-phenylalanyl-glycyl-glycine) as substrate, and an HPLC method using
      dansyltriglycine (DTG) as substrate. Hydrolysis of the insect protein resulted in
      an increased ACE inhibitory activity. Overall, the highest ACE inhibitory
      activity was obtained after gastrointestinal digestion. These results suggest a
      role for insect protein as antihypertensive component in functional foods and
      nutraceuticals. Furthermore, the ACE inhibitory activity differed according to
      the method used. As a consequence, there is a need to standardize methodologies
      to evaluate ACE inhibitory activity.

PMID- 15969499
TI  - Antioxidant activity of ethanolic extracts from several asparagus cultivars.
AB  - Three different methods (antiradical activity, inhibition of primary oxidation,
      and ferric reducing power) have been used to evaluate the antioxidant activity of
      eight different asparagus cultivars and byproducts: white and green asparagus
      from Alcala del Rio (Guadalquivir Valley, Seville) and American hybrids, native
      spears, and their byproducts from Huetor-Tajar (Vega de Granada). The correlation
      between antioxidant activity and total phenol content was studied. Six standards
      were also tested to validate the modified methods for antioxidant activity
      determination. Results obtained for antiradical capacity and reducing power were
      very similar, and a high correlation with phenols was found (R > or = 0.9 for
      both tests). Sample origin was an important factor, spears from Huetor-Tajar
      having higher values (ARC between 7 and 10 and P(R) of 0.25-0.33) than those from
      Alcala del Rio (ARC 0.6-2 and P(R) of 0.05-0.07). Significant differences were
      found between spears with the same origin, suggesting that genetics are another
      factor to take into account. Asparagus inhibits lipid primary oxidation, but no
      correlation between the inhibition percentage and phenols was observed. Asparagus
      origin was the only factor that led to significant differences: samples from
      Huetor-Tajar had higher values (POIC between 18 and 32) than those from Alcala
      del Rio (POIC of 5-9). Byproducts from the canning industry at Huetor-Tajar were
      also assayed for antioxidant activity; the results obtained suggested that
      byproducts could be considered as an excellent source of natural antioxidants.

PMID- 15969500
TI  - Molecular cloning and characterization of oryzacystatin-III, a novel member of
      phytocystatin in rice (Oryza sativa L. japonica).
AB  - On the basis of cDNA sequences, we found that the calli of rice encodes an amino
      acid sequence that shares 56% and 89% identity, respectively, with oryzacystatin
      I and oryzacystatin-II. This sequence differs from that of oryzacystatin-II in
      the N-terminal region (Gln(7)-Ala(19) in the oryzacystatin-III numbering), and
      this region contained a glycine residue (Gly(14)), which is evolutionarily
      conserved in the cystatin superfamily. We named this novel protein oryzacystatin
      III. Nucleotide sequencing of the 5'-flanking region of the oryzacystatin-III
      gene showed that it is highly homologous to the oryzacystatin-II gene but
      distinct from the oryzacystatin-II locus. Oryzacystatin-III inhibited papain,
      ficin, and human cathepsin B. The inhibition constants for papain and ficin
      differ from those of oryzacystatin-I and -II, and cathepsin B activity is
      affected only by oryzacystatin-III, showing differences in the interaction of
      these inhibitors with enzymes. These data suggest that the above three inhibitors
      may play unique physiological roles in the regulations of rice cysteine
      proteinases.

PMID- 15969501
TI  - Oviposition responses of culex pipiens to a synthetic racemic Culex
      quinquefasciatus oviposition aggregation pheromone.
AB  - The oviposition pheromone of Culex quinquefasciatus was synthesized in a racemic
      form in a simple (five steps), efficient, high yielding (45% total yield), and
      low cost way (use of relatively low cost reagents). Our synthetic racemic
      pheromone (SRP) was tested in the laboratory for its bioactivity on Culex pipiens
      biotype molestus, which is a member of the species complex that Culex
      quinquefasciatusbelongs. In the testing conditions, bioactivity at the doses of
      0.01, 0.1, 1, and 10 microg per cage was found with the best bioactivity achieved
      at 1 mug per cage. The effectiveness of our SRP offers a capable tool for
      improving mosquito oviposition traps for surveillance or even control programs.

PMID- 15969502
TI  - Validation of recombinant and bovine chymosin by mass spectrometry.
AB  - Mass spectrometry has been used to map chymosin from a fermentative source. The
      copresence of the two known genetic variants A (Asp(244)) and B (Gly(244)) was
      ascertained in bovine chymosin. By contrast, either the A or the B genetic
      variant occurred in the three commercial samples of recombinant calf chymosin
      (RCC). Specific biomarker proteins were searched to identify the enzyme source,
      in both bovine chymosin and RCC samples. Analyzing the derived tryptic peptides,
      evidence was provided that RCC and bovine chymosin are mainly formed by (1-323),
      (3-323), and (40p-323) (suffix "p" denotes residues in the pro-segment region of
      chymosin), whereas the minor components, (4-323), (5-323), and (6-323), were only
      detected in bovine chymosin. Additionally, the three commercial RCC samples
      contained the protein species (1-323), (38p-323), (39p-323), and (40p-323) and
      the shorter form (3-323). Differentiation of the natural and bioengineered enzyme
      is based upon the detection of these unique minor components by mass
      spectrometry.

PMID- 15969503
TI  - ITS1-rDNA-based methodology to identify world-wide hake species of the Genus
      Merluccius.
AB  - Species-specific DNA-based tags are valuable tools for the management of both
      fisheries and commercial fish products. In this study, we have developed a two
      step molecular tool to detect the presence of hake DNA (Merluccius spp.) and to
      identify the exact hake species present in an blind sample. The first test
      involves PCR amplification of an ITS1-rDNA fragment of 193 bp using nested
      primers that are interspecifically conserved in Merluccius spp. and Atlantic cod,
      Gadus morhua. The second test consists of the PCR amplification of a 602-659 bp
      DNA fragment spanning part of the ribosomal cluster 18S-ITS1-5.8S and digesting
      it with four restriction enzymes whose targets map at interspecifically
      nonconserved sites of the ITS1. Alternatively, the identification of hake species
      can be achieved by FINS or BLAST, using the nucleotide sequence of either the
      whole ITS1 sequence or its nested fragment of 193 bp. Because of their high
      reproducibility and ease of execution, these procedures allow for routine
      analysis and constitute high reliable tools for the rapid identification of 12
      species of hake.

PMID- 15969504
TI  - Improving the nutritional value of crops through enhancement of L-ascorbic acid
      (vitamin C) content: rationale and biotechnological opportunities.
AB  - L-Ascorbic acid (AsA, vitamin C) is an essential human nutrient that must be
      obtained in the diet, with the vast majority being obtained from plant foods. A
      vitamin C-deficient diet results in the onset of scurvy, which can have lethal
      consequences. However, vitamin C has also been implicated in the prevention of
      chronic diseases such as heart disease, stroke, cancer, and several
      neurodegenerative diseases. Although the supporting evidence for these claims is
      disputed, the dietary allowances for vitamin C have been recently increased in
      several countries, including the United States. This scenario, together with the
      general perception by consumers of vitamin C as being of benefit in the
      prevention of several lifestyle diseases and associated with general "well
      being", contributes to a market rationale for enhancing the vitamin C content of
      crops. In recent years, there has been substantial progress in the understanding
      of vitamin C biochemistry in plants with a number of structural genes cloned.
      Here these findings are reviewed, and a description of how such knowledge could
      be applied to the nutritional enhancement of crops is given.

PMID- 15969505
TI  - Biological aging of sherry wines using pure cultures of two flor yeast strains
      under controlled microaeration.
AB  - Sherry wines obtained after biological aging for an average of 0, 2, and 4 years
      were inoculated separately with the flor yeast strains Saccharomyces cerevisiae
      var. capensis and Saccharomyces bayanus and subjected to short, periodic
      microaeration to a dissolved oxygen concentration of 4 mg L(-1) after formation
      of the yeast film. A principal component analysis with the acetaldehyde, ethanol,
      volatile acidity, and glycerol concentrations obtained was performed. The first
      principal component was found to account for 49.5% of the overall variance and to
      be defined mainly by glycerol and ethanol. The second component accounted for
      38.8% of the variance and was defined by volatile acidity and acetaldehyde. The
      conditions used in the tests allowed the biological aging of the wines to be
      substantially shortened. Thus, 42 days after flor-film formation by S. cerevisiae
      var. capensis, 0- and 2-year-old wines exhibited parameter values similar to
      those obtained for the wine aged for 4 years. The wines inoculated with S.
      bayanus exhibited high acetaldehyde concentrations and ethanol levels above 15%
      (v/v)-sherry wines with alcohol concentrations below 14.5% are undesirable-, so
      one need not exclude the sequential or simultaneous inoculation of S. bayanus
      together with S. cerevisiae var. capensis in order to improve the biological
      aging process.

PMID- 15969506
TI  - Novel method for the production of pure glycinin from soybeans.
AB  - A novel method for the purification of glycinin from soy meal is presented. The
      method is based on the isoelectric precipitation of glycinin by using carbon
      dioxide as a volatile precipitant. Gaseous CO(2) was pressurized into the protein
      solution, thus lowering the pH and initiating glycinin precipitation.
      Pressurization and, consequently, acidification were done in a slow and
      controlled manner, with the end point of pH 6.4. The acidity of the protein
      solution was well controlled via the pressure of gaseous CO(2). In this way
      simultaneous precipitation of other soybean proteins was prevented and very pure
      glycinin was obtained. Approximately 40% of the glycinin present in the protein
      solution was recovered with purity as high as 98%. The purification process was
      successfully performed on both small and large scales, without affecting glycinin
      purity.

PMID- 15969507
TI  - Migration studies to assess the safety in use of a new antioxidant active
      packaging.
AB  - Both specific and overall migration tests have been applied to new experimental
      food packaging-active plastic films with antioxidant properties, including in its
      composition a natural rosemary extract. Determination of volatile and
      semivolatile compounds migrating from plastic to the four established simulants
      showed that both specific and overall migration was very low. The results
      obtained gave values 20 times lower than the established limits in the worst
      case. So, from the point of view of health risk, the new active packaging can be
      considered as safe. Analytical procedure used provided the necessary information
      about the migration behavior, with good analytical characteristics and detection
      limits in the sub mug kg(-1) range. Besides, no significant difference was found
      between laboratory and factory-made samples, which is an important issue for
      industrial production, the next step in the development of the new antioxidant
      active film.

PMID- 15969508
TI  - Identification of dehydro-ferulic acid-tyrosine in rye and wheat: evidence for a
      covalent cross-link between arabinoxylans and proteins.
AB  - To monitor chemical reactions between ferulate and proteins during breadmaking, 8
      (14)C-(E)-ferulic acid-(d-galactopyranose-6'-yl)ester was synthesized as a
      radiotracer and added to wheat and rye flour prior to breadmaking. Breads were
      lyophilized, extracted by means of a modified Osborne fractionation, and the
      radioactivity of the fractions was determined by scintillation analysis. The
      major portion of the radioactivity remained in the water-soluble fraction.
      However, a significant enrichment of the tracer was also detected in the prolamin
      and glutelin fractions in comparison to the control experiment. Separation of the
      prolamin fraction by RP-HPLC and scintillation measurement of the fractions gave
      evidence for a chemical modification of the tracer. To determine the structure of
      the reaction product, the prolamin fractions were completely hydrolyzed to free
      amino acids by means of an enzyme cocktail, and the digests were studied by LC
      MS. In one fraction, a newly formed compound was detected. Comparison of its
      chromatographic and mass spectrometric behavior with a synthetic reference
      compound gave evidence that the newly identified compound was a dehydroferulic
      acid-tyrosine cross-link. It is likely that this cross-link represented a
      covalent linkage between arabinoxylans and cereal proteins. The newly identified
      cross-link was also identified in wheat and rye flour doughs, which had been
      prepared without addition of the ferulate tracer. The relative concentration of
      the dehydroferulic acid-tyrosine cross-link increased during wheat dough
      preparation.

PMID- 15969509
TI  - Kinetic study of the physicochemical and microbiological changes in "seasoned"
      olives during the shelf-life period.
AB  - The changes that take place during the shelf life of "seasoned" olives (packing
      conditions: 4% NaCl, 0.1%citric acid, and 0.0175% sorbate) using fresh (FF) and
      stored (SF) cracked fruits were studied. Texture, L, b, NaCl, and pH experienced
      slight changes. Values of a and titratable and combined acidity increased
      following a first-order kinetic with higher constants for FF. Glucose was
      completely exhausted, and mannitol showed only a slight decline. Hydroxytyrosol
      and tyrosol contents in brines increased rapidly from the acidic hydrolysis of
      oleuropein, hydroxytyrosol-4-beta -d-glucoside, and salidroside, the
      concentrations of which decreased. Sorbate content decreased with time and
      disappeared completely in SF. Yeasts grew rapidly in FF and were markedly
      inhibited in SF. There was a moderate growth of lactic acid bacteria in FF,
      whereas they grew markedly in SF during the first few days. Some of these changes
      limit the shelf life of the product.

PMID- 15969510
TI  - Authenticity of the traditional cypriot spirit "zivania" on the basis of 1h NMR
      spectroscopy diagnostic parameters and statistical analysis.
AB  - A previous publication (Kokkinofta et al. J. Agric. Food Chem. 2003, 51, 6233
      6239) discussed the use of inductively coupled plasma spectroscopy to
      differentiate between the traditional Cypriot alcoholic beverage zivania and
      other spirits similar in alcoholic content collected from different countries. In
      the present paper (1)H NMR spectroscopy is applied to confirm the previous
      conclusions and to obtain additional physical-chemical characteristics that may
      be used to differentiate zivania from other similar beverages. NMR spectroscopy
      gave a satisfactory degree of prediction and classification between zivanias and
      other distillings. The validity of quantification of the method was tested using
      comparative GC data. It appears that chemical analysis can be very helpful for
      identifying the unique geological and climatic conditions existing in the island
      of Cyprus that lead to an authentic product.

PMID- 15969511
TI  - Chemometric discrimination among wild and cultured age-0 largemouth bass, black
      crappies, and white crappies based on fatty acid composition.
AB  - The potential to distinguish juvenile wild from cultured fishes and to
      discriminate among juvenile fishes by species based on fatty acid composition was
      demonstrated. Statistical approaches to data evaluation included analysis of
      variance, correlation analysis, principal component analysis (PCA), and quadratic
      discriminant analysis (QDA). Differences were determined between wild and
      cultured fishes both within and between species and between hatcheries. Fatty
      acid compositions were compared among individual (not composited) specimens of
      wild and cultured, age-0, freshwater species: largemouth bass Micropterus
      salmoides, black crappies Pomoxis nigromaculatus, white crappies P. annularis,
      and black-nose crappies. Four fatty acids were investigated: linoleic acid (18:2n
      6), linolenic acid (18:3n-3), arachidonic acid (20:4n-6), and docosahexaenoic
      acid (22:6n-3). Linoleic acid was the primary fatty acid used to differentiate
      juvenile wild from cultured fishes. Concentrations of linoleic acid were
      significantly different (p < 0.05) in cultured largemouth bass and black crappies
      from the wild counterparts. Linolenic acid concentrations were not significantly
      different (p < 0.05) between wild and cultured largemouth bass but were
      significantly different between wild and cultured black crappies. Wild largemouth
      bass contained higher concentrations of arachidonic acid than the cultured bass,
      and concentrations of docosahexaenoic acid were twice as high in wild black
      crappies than cultured black crappies. On the basis of four signature fatty
      acids, 90 of 91 juvenile fishes were correctly classified as wild or cultured; 32
      of 37 wild juvenile fishes originating from the same reservoir were
      differentiated by species. Data from the training set were used to classify a
      test set of fishes as to species, source, or origin with 100% accuracy.

PMID- 15969512
TI  - Influence of incorporated wild Solanum genomes on potato properties in terms of
      starch nanostructure and glycoalkaloid content.
AB  - Interspecific somatic hybrids produced by protoplast fusion between two wild
      Solanum species (S. acaule, acl; S. brevidens, brd) and cultivated potato Solanum
      tuberosum (tbr) were analyzed in terms of the starch nanometer-range structure
      and glycoalkaloid (GA) contents. The crystallinity of starch granules, the
      average size of starch crystallites, and the lamellar distances were obtained
      from tuber samples using wide-angle and small-angle X-ray scattering methods.
      These measurements showed that incorporation of wild genomes from either
      nontuberous (brd) or tuberous (acl) Solanum species caused no significant
      modifications of the nanostructure of potato starch. In contrast, the GA profiles
      of the hybrids, which were analyzed by LC-ESI-MS in both tuber and foliage
      samples, differed considerably from those of cultivated potato. Regardless of the
      low total tuber GA concentrations (approximately 9 mg/100 g of fresh weight), the
      somatic hybrids contained GAs not detected in the parental species. A high
      proportion of spirotype GAs consisting of 5,6-dihydrogenated aglycons, for
      example, alpha-tomatine and tomatidine bound with solatriose, and chacotriose
      were found in the hybrids. In conclusion, the foliage of interspecific hybrids
      contained a higher variation in the structures of GAs than did the tubers.

PMID- 15969513
TI  - Oils from improved high stearic acid sunflower seeds.
AB  - Seed oils from new recombinant high-stearic sunflower lines (Helianthus annuus
      L.) have been characterized. These new lines were generated by crossing high
      stearic acid lines between themselves or by crossing them with standard and high
      oleic sunflower lines. Of the novel lines generated, the lines CAS-29 and CAS-30
      are on a standard background and contain up to 34.5% of stearic acid. In
      contrast, CAS-15 and CAS-33 are on a high oleic acid background and contain only
      24.9 and 17.4% of stearic acid, respectively. The stearic acid contents of lines
      CAS-19 and CAS-20 are 10.0 and 21.5%, respectively, and they have only one of the
      two genes that control the high stearic acid trait. In accordance with their
      vegetable origin, these lines have a low percentage of stearic acid in the sn-2
      position of the TAGs, from 0.6 to 2.1%. The amount of disaturated TAGs increases
      with the stearic acid content, from 1.8% in the standard line to between 5.1% in
      CAS-20 and 38.5% in CAS-29. There was also a concomitant reduction in
      triunsaturated TAGs, which were reduced to levels as low as 8.4% in CAS-29, as
      opposed to the 67.9% that they constitute in the standard line RHA-274. The
      asymmetrical distribution of the saturated fatty acids between the sn-1 and sn-3
      TAG positions ranges from 0.26 to 0.36, being lower in those lines with higher
      oleic acid content.

PMID- 15969514
TI  - Glyphosate-tolerant soybeans remain compositionally equivalent to conventional
      soybeans (Glycine max L.) during three years of field testing.
AB  - Previous studies have shown that the composition of glyphosate-tolerant soybeans
      (GTS) and selected processed fractions was substantially equivalent to that of
      conventional soybeans over a wide range of analytes. This study was designed to
      determine if the composition of GTS remains substantially equivalent to
      conventional soybeans over the course of several years and when introduced into
      multiple genetic backgrounds. Soybean seed samples of both GTS and conventional
      varieties were harvested during 2000, 2001, and 2002 and analyzed for the levels
      of proximates, lectin, trypsin inhibitor, and isoflavones. The measured analytes
      are representative of the basic nutritional and biologically active components in
      soybeans. Results show a similar range of natural variability for the GTS
      soybeans as well as conventional soybeans. It was concluded that the composition
      of commercial GTS over the three years of breeding into multiple varieties
      remains equivalent to that of conventional soybeans.

PMID- 15969515
TI  - Quantification of imidacloprid uptake in maize crops.
AB  - The systemic imidacloprid is one of the most used insecticides in the world for
      field and horticultural crops. This neurotoxicant is often used as seed-dressing,
      especially for maize, sunflower, and rape. Using a LC/MS/MS technique (LOQ = 1
      microg/kg and LOD = 0.1 microg/kg), the presence of imidacloprid has been
      measured in maize from field samples at the time of pollen shed, from less than
      0.1 microg/kg up to 33.6 microg/kg. Numerous random samples were collected
      throughout France from 2000 to 2003. The average levels of imidacloprid measured
      are 4.1 microg/kg in stems and leaves, 6.6 microg/kg in male flowers (panicles),
      and 2.1 microg/kg in pollen. These values are similar to those found previously
      in sunflower and rape. These results permit evaluation of the risk to honeybees
      by using the PEC/PNEC ratios (probable exposition concentrations/predicted no
      effect concentration). PEC/PNEC risk ratios were determined and ranged between
      500 and 600 for honeybees foraging on maize treated with imidacloprid by seed
      dressing. Such a high risk factor can be related to one of the main causes of
      honeybee colony losses.

PMID- 15969516
TI  - Residues of the lampricides 3-trifluoromethyl-4-nitrophenol and niclosamide in
      muscle tissue of rainbow trout.
AB  - Rainbow trout (Oncorhyncus mykiss) were exposed to the (14)C-labeled lampricide 3
      trifluoromethyl-4-nitrophenol (TFM) (2.1 mg/L) or niclosamide (0.055 mg/L) in an
      aerated static water bath for 24 h. Fish were sacrificed immediately after
      exposure. Subsamples of skin-on muscle tissue were analyzed for residues of the
      lampricides. The primary residues in muscle tissue from fish exposed to TFM were
      parent TFM (1.08 +/- 0.82 nmol/g) and TFM-glucuronide (0.44 +/- 0.24 nmol/g).
      Muscle tissue from fish exposed to niclosamide contained niclosamide (1.42 +/-
      0.51 nmol/g), niclosamide-glucuronide (0.0644 +/- 0.0276 nmol/g), and a
      metabolite not previously reported, niclosamide sulfate ester (1.12 +/- 0.33
      nmol/g).

PMID- 15969517
TI  - Abiotic degradation of iodosulfuron-methyl-ester in aqueous solution.
AB  - The abiotic degradation of iodosulfuron-methyl-ester was investigated under both
      alkaline and acidic pH conditions in the dark, and results showed it to be a
      rather stable molecule in neutral or slightly alkaline environments.
      Photochemical reactions were studied using a high-pressure mercury arc lamp, and
      results showed that direct phototransformation is possible under normal
      environmental conditions (lambda > 290 nm). High-performance liquid
      chromatography (HPLC-UV and HPLC-MS) analyses were used to identify the
      degradates and to study the kinetics of photodecomposition and hydrolysis. Five
      main products of iodosulfuron-methyl-ester degradation were tentatively
      identified, and one of them (4-methoxy-6-methyl-1,3,5-triazin-2-amine) was
      confirmed using an authentic standard. Among the phototransformation mechanisms,
      photosubstitution of the iodide atom by a hydroxyl group, photodissociation of
      the N-S bond, and photoassisted hydrolysis were observed. The quantum
      efficiencies (multiwavelength quantum yield) of the photodegradation under
      different conditions were determined, and values of 0.054 +/- 0.02 (pH 9.6), 0.08
      +/- 0.02 (pH 7), and 0.044 +/- 0.008 (pH 5.3) were obtained.

PMID- 15969518
TI  - Tomato metabolism and porphyrin-catalyzed oxidation of pyriproxyfen.
AB  - Investigation of the metabolism of [(14)C]pyriproxyfen [4-phenoxyphenyl (R,S)-2
      (2-pyridyloxy)propyl ether] in tomato fruits (Lycopersicon esculentum Mill. cv.
      Ponterosa) was conducted by topical application of acetonitrile solution or
      emulsifiable concentration formulation three times at 35, 21, and 7 days before
      harvest. Most of the radioactivity remained on the fruit surface or in the plant
      tissues as intact pyriproxyfen with minor metabolites formed via hydroxylation at
      the 4'-position of the phenoxy ring or cleavage of ether linkages. The biomimic
      chemical oxidation model using iron porphyrin as a catalyst and hydrogen peroxide
      was found to well reproduce the primary metabolites detected in the metabolism
      study. The electrophilic reaction indices obtained by AM1 molecular orbital
      calculations supposing involvement of cytochrome P-450 were successfully applied
      to evaluate the potentially higher reactive sites in pyriproxyfen.

PMID- 15969519
TI  - Sorption-desorption of alachlor and linuron in a semiarid soil as influenced by
      organic matter properties after 16 years of periodic inputs.
AB  - The effect of management practices on soil potential for regulating the residual
      concentration of pesticides was examined in samples from a Calcic Haploxeralf in
      Toledo (central Spain). Sorption-desorption of alachlor and linuron was found to
      depend on inputs of lignocelullosic wastes or cattle manure for the past 16
      years. For a given herbicide, the soil sorption capacity (K(f)) follows the order
      control < crop residues < manure, which is consistent with the organic C content
      in the soil samples. Some structural characteristics of the soil humic acid as
      revealed by visible and infrared spectroscopies and analytical pyrolysis were
      useful to forecast the sorption-desorption intensity. Simple and multiple linear
      correlation analyses illustrate enhanced sorption of alachlor and linuron in soil
      plots where slightly altered soil organic matter accumulated (positive
      correlations with the intensity of infrared lignin signature band and with the
      methoxyphenol yields after pyrolysis of the humic acids and negative correlation
      with the aromaticity as pointed out by the optical density at 465 nm). Linuron
      showed a preference for soils with humic acids of low molecular weight and low
      degree of internal cross-linking, as inferred from the positive correlation with
      the ratio between optical densities at 465 and 665 nm. Under the conditions of
      the present experiment, agricultural practices including organic amendments seem
      to have a beneficial effect in the control of leaching and sorption of
      pesticides.

PMID- 15969520
TI  - Improvement of the desorption of the herbicide norflurazon from soils via
      complexation with beta-cyclodextrin.
AB  - The effect of beta-cyclodextrin (beta-CD) on the removal of the herbicide
      norflurazon (NFL) from soils has been investigated. The interaction of NFL with
      beta-CD in solution yielded the formation of a water-soluble inclusion complex at
      1:1 stoichiometric ratio, which gave an increase in NFL solubility. Desorption
      studies of NFL previously adsorbed on six soils of different characteristics have
      been performed in the presence of 0.01 M beta-CD or 0.01 M Ca(NO(3))(2) as
      extractant solutions. Positive hysteresis was observed in all soils when 0.01 M
      Ca(NO(3))(2) solution was used, indicating that desorption of NFL from these
      soils was not completely reversible. On the contrary, the application of beta-CD
      solutions to soils where NFL had been previously adsorbed increased very much its
      desorption, and a negative hysteresis was obtained for all soils studied; that
      is, more NFL was desorbed with respect to NFL adsorption isotherm. A clear
      relationship was observed between the physicochemical characteristics of the
      soils and the beta-CD concentration necessary to remove the herbicide, the
      percentages of desorption observed for each soil being inversely related to the
      values obtained for the Freundlich sorption capacity parameter of the herbicide,
      K(f). In general, high desorption yields can be obtained with very low beta-CD
      concentrations, which is an important advantage from an economic point of view,
      although in those soils that present an extremely high NFL adsorption, higher
      amounts of beta-CD should be used. The results obtained indicate the high
      extracting power of beta-CD toward the herbicide previously adsorbed on the soils
      and the potential use of beta-CD for in situ remediation of pesticide
      contaminated soils.

PMID- 15969521
TI  - Adsorption and analysis of the insecticides thiamethoxam and indoxacarb in
      hawaiian soils.
AB  - A method was developed for the simultaneous extraction and analysis of the
      insecticides indoxacarb and thiamethoxam from five Hawaiian soils. Using
      pressurized fluid extraction followed by liquid chromatography, optimized
      recoveries from the five soils were obtained ranging from 80% +/- 5 to 101% +/-
      10 for thiamethoxam, and 83% +/- 6 to 106% +/- 7 for indoxacarb. Aging studies
      also showed strong binding of indoxacarb to all soils tested after 30 days, while
      thiamethoxam remained quite available for extraction during the length of the
      study (90 days). Freundlich constant (K(f)) and empirical value (n) for
      thiamethoxam sorption on Lihue soil were 0.007391 mmol((1-1/)(n)).L(1/)(n).g(-1)
      and 1.1377, respectively; K(f) and n were 0.007844 mmol((1-1/)(n)).L(1/)(n).g(-1)
      and 0.8473, respectively, on Wahiawa soil. The organic carbon adsorption constant
      (Koc) of thiamethoxam was 0.53 in Lihue soil and 0.23 in Wahiawa soil.

PMID- 15969522
TI  - Molecular definition of black tea taste by means of quantitative studies, taste
      reconstitution, and omission experiments.
AB  - Recently, bioresponse-guided fractionation of black tea infusions indicated that
      neither the high molecular weight thearubigens nor the theaflavins, but a series
      of 14 flavon-3-ol glycopyranosides besides some catechins, might be important
      contributors to black tea taste. To further bridge the gap between pure
      structural chemistry and human taste perception, in the present investigation 51
      putative taste compounds have been quantified in a black tea infusion, and their
      dose-over-threshold (Dot) factors have been calculated on the basis of a
      dose/threshold relationship. To confirm these quantitative results, an aqueous
      taste model was prepared by blending aqueous solutions of 15 amino acids, 14
      flavonol-glycosides, 8 flavan-3-ols, 5 theaflavins, 5 organic acids, 3 sugars,
      and caffeine in their "natural" concentrations. Sensory analyses revealed that
      the taste profile of this artificial cocktail did not differ significantly from
      the taste profile of the authentic tea infusion. To further narrow the number of
      key taste compounds, finally, taste omission experiments have been performed, on
      the basis of which a reduced recombinate was prepared containing the bitter
      tasting caffeine, nine velvety astringent flavonol-3-glycosides, and the
      puckering astringent catechin as well as the astringent and bitter
      epigallocatechin-3-gallate. The taste profile of this reduced recombinate
      differed not significantly from that of the complete taste recombinate, thus
      confirming these 12 compounds as the key taste compounds of the tea infusion.
      Additional sensory studies demonstrated for the first time that the flavanol-3
      glycosides not only impart a velvety astringent taste sensation to the oral
      cavity but also contribute to the bitter taste of tea infusions by amplifying the
      bitterness of caffeine.

PMID- 15969523
TI  - Volatile components and key odorants of fennel (Foeniculum vulgare Mill.) and
      thyme (Thymus vulgaris L.) oil extracts obtained by simultaneous distillation
      extraction and supercritical fluid extraction.
AB  - Volatile oil extracts of fennel seeds (Foeniculum vulgare Mill.) and thyme leaves
      (Thymus vulgaris L.) were obtained by simultaneous distillation-extraction (SDE)
      and supercritical fluid extraction (SFE) and analyzed by gas chromatography-mass
      spectrometry (GC-MS). In general, fennel oil extracted by SDE and SFE showed
      similar compositions, with trans-anethole, estragole, and fenchone as the main
      components. In contrast, thymol and p-cymene, the most abundant compounds in
      thyme leaves, showed big differences, with generally higher amounts of
      monoterpenes obtained by SDE. However, in this case, the differences between the
      extracts were higher. Key odorants of fennel seeds determined by gas
      chromatography-olfactometry (GC-O) showed similar patterns when applying SDE and
      SFE. trans-Anethole (anise, licorice), estragole (anise, licorice, sweet),
      fenchone (mint, camphor, warm), and 1-octen-3-ol (mushroom) were the most intense
      odor compounds detected in fennel extracts. Thymol and carvacrol, with oregano,
      thyme, and spicy notes, were identified as key compounds contributing to the
      aroma of thyme leaves.

PMID- 15969524
TI  - Influence of manufacturing conditions and crop season on the formation of 4
      mercapto-4-methyl-2-pentanone in Japanese green tea (sen-cha).
AB  - 4-Mercapto-4-methyl-2-pentanone is one of the most strongly contributing odorants
      in the volatile fraction of a Japanese green tea (sen-cha) infusion, and on the
      basis of the results of an aroma extract dilution analysis, the contribution of
      this compound to the flavor of the sen-cha infusion varied according to the
      degree of heating of the tea leaves during the roasting process. The
      concentration of this odorant in the sen-cha infusion, as with other roasty
      odorants, increased with the increasing roasting temperature. However, the slope
      of the increase curve differed with the odor compound, and even if roasting was
      done at a low temperature, at which the other roasty odorants hardly increased, 4
      mercapto-4-methyl-2-pentanone still increased and reached a maximum at 112
      degrees C. On the other hand, the amount of 4-mercapto-4-methyl-2-pentanone in
      sen-cha was a maximum in the first crop, then decreasing in the order of the
      second and third crops. These results suggested that the amount of 4-mercapto-4
      methyl-2-pentanone was closely involved with the quality of sen-cha and that the
      concentration was dependent on the roasting conditions for the green tea leaves,
      which might be accompanied by an enzymatic reaction.

PMID- 15969525
TI  - Authenticity assessment of gamma- and delta-decalactone from prunus fruits by gas
      chromatography combustion/pyrolysis isotope ratio mass spectrometry (GC-C/P
      IRMS).
AB  - Authenticity assessment of gamma-decalactone (1) and delta-decalactone (2) from
      peach (Prunus persica var. persica), apricot (Prunus armeniaca), and nectarine
      (Prunus persica var. nectarina) was performed using gas chromatography-isotope
      ratio mass spectrometry (GC-IRMS) in the combustion (C) and pyrolysis (P) mode.
      In addition, commercially available synthetic (nature-identical) 1 and 2 as well
      as biotechnologically produced samples (declared to be "natural") were
      characterized by their delta(2)H(V)(-)(SMOW) and delta(13)C(V)(-)(PDB) values.
      For the Prunus fruits under study, rather narrow ranges of delta(13)C(V)(-)(PDB)
      and delta(2)H(V)(-)(SMOW) data of 1, varying from - 34.6 per thousand to - 38.4
      per thousand and -160 per thousand to -206 per thousand, respectively, were
      obtained. Synthetic references of 1 showed delta(13)C(V)(-)(PDB) and
      delta(2)H(V)(-)(SMOW) data ranging from -27.4 per thousand to -28.3 per thousand
      and -151 per thousand to -184 per thousand, respectively. Samples of 1 declared
      to be "natural" exhibited ranges from -28.1 per thousand to -29.2 per thousand
      and -192 per thousand to -286 per thousand for delta(13)C(V)(-)(PDB) and
      delta(2)H(V)(-)(SMOW), respectively. For 2 from peach, apricot, and nectarine,
      delta(13)C(V)(-)(PDB) values ranging from -34.0 per thousand to -37.9 per
      thousand were determined; the delta(2)H(V)(-)(SMOW) values ranged from -171 per
      thousand to -228 per thousand. The delta(13)C(V)(-)(PDB) and delta(2)H(V)(
      )(SMOW) data for synthetic 2 were -28.2 per thousand and -171 per thousand,
      respectively, that is, similar to those of 2 from "natural" origin, ranging from 
      27.7 per thousand to -30.1 per thousand and -185 per thousand to -230 per
      thousand for delta(13)C(V)(-)(PDB) and delta(2)H(V)(-)(SMOW), respectively. GC
      C/P-IRMS allowed clear-cut analytical differentiation of the synthetic and "ex
      plant" origin of 1 and 2, whereas narrow ranges of delta(13)C(V)(-)(PDB) and
      delta(2)H(V)(-)(SMOW) data were found for samples of synthetic and "natural"
      origin.

PMID- 15969526
TI  - Interaction of cyclodextrins with aliphatic acetate esters and aroma components
      of La France pear.
AB  - The interaction between aliphatic acetate esters, which are the major flavor
      components of La France pear (Pyrus communis L.), and cyclodextrins (CDs) was
      studied to obtain fundamental data for preparing powdered pear flavor materials.
      The complexing abilities of alpha-, beta-, or gamma-CD with six kinds of
      aliphatic acetate esters were compared. alpha-CD formed the highest numbers of
      complexes with all of the esters. All of the CDs produced complexes more readily
      with the more hydrophobic esters. Among our samples of freeze-dried pear juice
      containing dissolved alpha-, beta-, or gamma-CD, the juice with alpha-CD retained
      the greatest amount of esters. These data demonstrate that alpha-CD is an
      effective material with which to prepare powdered pear flavor materials. The
      nuclear Overhauser effect, measured by (1)H NMR spectra, of an alpha-CD-butyl
      acetate or alpha-CD-hexyl acetate complex showed that these esters were included
      in the alpha-CD cavity.

PMID- 15969527
TI  - Sensory-guided decomposition of roasted cocoa nibs (Theobroma cacao) and
      structure determination of taste-active polyphenols.
AB  - Sequential application of solvent extraction, gel permeation chromatography, and
      RP-HPLC in combination with taste dilution analyses, followed by LC-MS and 1D/2D
      NMR experiments and thiolytic degradation, revealed that, besides theobromine and
      caffeine, the flavan-3-ols epicatechin, catechin, procyanidin B-2, procyanidin B
      5, procyanidin C-1, [epicatechin-(4beta-->8)](3)-epicatechin, and [epicatechin
      (4beta-->8)](4)-epicatechin were among the key compounds contributing to the
      bitter taste as well as the astringent mouthfeel imparted upon consumption of
      roasted cocoa. In addition, a series of quercetin, naringenin, luteolin, and
      apigenin glycopyranosides as well as a family of not previously identified amino
      acid amides, namely, (+)-N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N
      [3',4'-dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (-)-N-[3',4'-dihydroxy-(E)
      cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)
      N-[4'-hydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine, (+)-N-[4'-hydroxy-3'-methoxy
      (E)-cinnamoyl]-L-aspartic acid, and (+)-N-(E)-cinnamoyl-L-aspartic acid, have
      been identified as key astringent compounds of roasted cocoa. Furthermore, (-)-N
      [3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-l-tyrosine (clovamide), (-)-N-[4'
      hydroxy-(E)-cinnamoyl]-L-tyrosine (deoxyclovamide), and (-)-N-[3',4'-dihydroxy
      (E)-cinnamoyl]-L-tyrosine, reported previously as antioxidants, have been found
      as contributors of cocoa's astringent taste. By means of the half-tongue test,
      the taste thresholds of flavan-3-ols and glycosides have been determined.

PMID- 15969528
TI  - Isolation, structure determination, synthesis, and sensory activity of N
      phenylpropenoyl-L-amino acids from cocoa (Theobroma cacao).
AB  - Application of chromatographic separation and taste dilution analyses recently
      revealed besides procyanidins a series of N-phenylpropenoyl amino acids as the
      key contributors to the astringent taste of nonfermented cocoa beans as well as
      roasted cocoa nibs. Because these amides have as yet not been reported as key
      taste compounds, this paper presents the isolation, structure determination, and
      sensory activity of these amino acid amides. Besides the previously reported (-)
      N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine (clovamide), (-)-N-[4'
      hydroxy-(E)-cinnamoyl]-L-tyrosine (deoxyclovamide), and (-)-N-[3',4'-dihydroxy
      (E)-cinnamoyl]-L-tyrosine, seven additional amides, namely, (+)-N-[3',4'
      dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N-[4'-hydroxy-(E)-cinnamoyl]-L
      aspartic acid, (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'
      hydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-3
      hydroxy-L-tyrosine, (+)-N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-aspartic acid,
      and (+)-N-[(E)-cinnamoyl]-L-aspartic acid, were identified for the first time in
      cocoa products by means of LC-MS/MS, 1D/2D-NMR, UV-vis, CD spectroscopy, and
      polarimetry, as well as independent enantiopure synthesis. Using the recently
      developed half-tongue test, human recognition thresholds for the astringent and
      mouth-drying oral sensation were determined to be between 26 and 220 micromol/L
      (water) depending on the amino acid moiety. In addition, exposure to light
      rapidly converted these [E]-configured N-phenylpropenoyl amino acids into the
      corresponding [Z]-isomers, thus indicating that analysis of these compounds in
      food and plant materials needs to be performed very carefully in the absence of
      light to prevent artifact formation.

PMID- 15969529
TI  - Protection against oxidation of fish-oil-enriched milk emulsions through addition
      of rapeseed oil or antioxidants.
AB  - The ability of rapeseed oil and/or different antioxidants (alpha- and gamma
      tocopherol mixture, ascorbyl palmitate, and EDTA) to protect fish-oil-enriched
      milk emulsions against oxidation was investigated. Tocopherol isomers in
      concentrations similar to those found in natural rapeseed oil were added to
      rapeseed oil stripped of natural tocopherols. The rapeseed oil with added
      tocopherols significantly inhibited oxidation in the fish-oil-enriched milk
      emulsions. In contrast, the emulsions with only fish oil and added alpha- and
      gamma-tocopherol were less stable than the emulsions with fish oil alone. When
      added individually, the gamma-tocopherol seemed to inhibit oxidation more
      efficiently than alpha-tocopherol. Ascorbyl palmitate (AP) almost completely
      retarded oxidation in the fish-oil-enriched milk emulsions, as determined by PV,
      volatile oxidation products, and sensory evaluation. AP also prevented the
      otherwise prooxidant effect of tocopherols added to fish oil before
      emulsification. No interactions between AP, tocopherols, and EDTA were observed,
      and EDTA added alone to fish oil did not show antioxidant properties in the milk
      emulsions. Overall, the results showed that addition of AP or rapeseed oil
      containing natural tocopherols to fish oil was equally efficient in inhibiting
      oxidation in the fish-oil-enriched milk emulsions.

PMID- 15969530
TI  - Degradation of phytate by high-phytase Saccharomyces cerevisiae strains during
      simulated gastrointestinal digestion.
AB  - Hydrolysis of extracellular phytate (InsP(6)) by high-phytase yeast strains and
      survival of yeast cells were studied at simulated digestive conditions using
      yeast peptone dextrose growth medium and wheat gruel as model meals. An in vitro
      digestion method was modified to better correlate with the gastric pH gradient
      following food intake in vivo. High-phytase yeast gave a strong reduction of
      InsP(6) (up to 60%) in the early gastric phase, as compared to no degradation by
      wild-type strains. The degree of InsP(6) degradation during digestion was
      influenced by the type of yeast strain, cell density, and InsP(6) concentration.
      Despite high InsP(6) solubility, high resistance against proteolysis by pepsin,
      and high cell survival, degradation in the late gastric and early intestinal
      phases was insignificant. Dependency on pH for phytase expression and/or activity
      seemed thus to be an important limiting factor. Although further studies are
      needed, our results show the potential of using yeast as a phytase carrier in the
      gastrointestinal tract.

PMID- 15969531
TI  - Characteristics of an aminopeptidase from Japanese cedar (Cryptomeria japonica)
      pollen.
AB  - A peptidase from Japanese cedar pollen, Jc-peptidase, was clarified to
      preferentially hydrolyze an MCA substrate of Phe-MCA (L-phenylalanyl-4
      methylcoumaryl-7-amide). This study examined substrate specificities of Jc
      peptidase using oligopeptides. Jc-peptidase hydrolyzed Phe-Phe and Tyr-Phe
      effectively and hydrolyzed Leu-Phe, Met-Phe, and Arg-Phe moderately. Other
      substrates such as Ala-Phe, Asp-Phe, and Pro-Phe were not hydrolyzed with the
      peptidase. Results obtained with a series of aminoacyl-Phe peptides were
      compatible with the facts obtained for MCA substrates except for Arg-MCA. Effects
      of amino acid residues in the P1' position were also examined using Phe-amino
      acids. An N-terminal phenylalanine residue was actually released from bioactive
      peptides such as molluscan cardioexcitatory neuropeptide (FMRF-NH(2)). Because
      the activity was inhibited with Zn(2+) and EDTA, Jc-peptidase was inferred to
      belong to the metalloproteases. The N-terminal amino acid sequence was determined
      to be APIGVQLEIEENYVHMYNGF and an internal sequence to be EIFAATFNVDEETEA, but no
      homology with other proteins was found.

PMID- 15969532
TI  - Mitochondrial reduction of metmyoglobin: dependence on the electron transport
      chain.
AB  - Reduction of ferric myoglobin (metmyoglobin, MetMb) to its ferrous form is
      important for maintaining fresh meat color because only reduced myoglobin can
      bind oxygen to form the consumer-preferred cherry red color in fresh meat. The
      objective of this study was to characterize an apparent mitochondria electron
      transport chain (ETC)-linked pathway for MetMb reduction in vitro. MetMb was
      reduced in the presence of mitochondria and succinate (p < 0.05); mitochondria or
      succinate alone did not facilitate MetMb reduction relative to controls (p >
      0.05). Flushing samples with oxygen greatly decreased MetMb reduction, while
      flushing with argon increased MetMb reduction when compared with controls (p <
      0.05). ETC inhibitors were used to localize the site where electrons became
      available for MetMb reduction. MetMb reduction was increased by rotenone addition
      and decreased by malonic acid (p < 0.05); the reduction was completely abolished
      by additions of antimycin A or myxothiazol when compared with controls (p <
      0.05). These results suggest that electrons become available for MetMb reduction
      at a site(s) between complex III and IV. Mitochondrial ETC-linked MetMb reduction
      increased with increased mitochondrial density and succinate concentration (p <
      0.05); the greatest MetMb reduction was observed at pH 7.2 and 37 degrees C, and
      ETC-linked MetMb reducing activity decreased with time postmortem (p < 0.05).
      These results indicate that ETC-linked MetMb reduction exists but would be
      minimally active in postmortem muscles.

PMID- 15969533
TI  - Direct evidence for the function of FUM13 in 3-ketoreduction of mycotoxin
      fumonisins in Fusarium verticillioides.
AB  - Fumonisins are mycotoxins produced by Fusarium verticillioides, a widespread
      pathogen of corn. Although the gene cluster for the biosynthesis of fumonisins
      has been cloned, the majority of the genes have not been biochemically
      characterized. Here, we report the biochemical characterization of FUM13, a gene
      that encodes a short-chain dehydrogenase/reductase required for fumonisin
      biosynthesis. FUM13 has been expressed in E. coli, and the produced protein,
      Fum13p, has been purified. When the protein was incubated with 3-keto fumonisin
      B(3) (FB(3)) in the presence of NADPH, FB(3) was produced. The data provide
      direct evidence for the role of FUM13 in the 3-ketoreduction of fumonisins. In a
      functional complementation experiment, FUM13 gene was introduced into tsc10
      mutants of the yeast Saccharomyces cerevisiae, which carry a mutation in the 3
      ketosphinganine reductase gene in the sphingolipid pathway. The tsc10 mutants
      were not able to grow on the selection medium, but the same mutants transformed
      with FUM13 were able to grow. The results further confirm the function of FUM13
      in 3-ketoreduction in vivo.

PMID- 15969534
TI  - Dihydrocaffeoyl polyamines (kukoamine and allies) in potato (Solanum tuberosum)
      tubers detected during metabolite profiling.
AB  - Four related phenolic amides previously undescribed from the species were
      revealed during metabolic profiling of potato (Solanum tuberosum) tubers.
      N(1),N(12)-Bis(dihydrocaffeoyl)spermine (kukoamine A) and N(1),N(8)
      bis(dihydrocaffeoyl)spermidine were positively identified by comparison with
      authentic standards, while the structures N(1),N(4),N(12)
      tris(dihydrocaffeoyl)spermine and N(1),N(4),N(8)-tris(dihydrocaffeoyl)spermidine
      are proposed for the other two metabolites. Each amide was present at several
      tens of micrograms per gram of dry matter. Several of these compounds were
      subsequently detected in other solanaceous species, such as tomato (Lycopersicon
      esculentum) and Nicotiana sylvestris. They appeared not to be present in
      Arabidopsis thaliana or Beta vulgaris. Bis(dihydrocaffeoyl)spermine isomers have
      previously been identified in only a single plant, the Chinese medicinal species
      Lycium chinense (Solanaceae), where they may account for some of the described
      biological activity. The other compounds have not until now been reported in
      vivo, though some of the equivalent hydroxycinnamoyl derivatives are known. The
      surprising discovery of kukoamine and allies in a range of solanaceous species
      including potato, a common food crop that has a long history of scientific
      investigation, provides exemplary evidence for the potential of the nontargeted
      techniques of metabolomics in studying plant metabolites.

PMID- 15969535
TI  - Vitamin E composition of walnuts (Juglans regia L.): a 3-year comparative study
      of different cultivars.
AB  - The tocopherol and tocotrienol composition of walnuts (Juglans regia L.) was
      determined for nine cultivars (cvs. Arco, Franquette, Hartley, Lara, Marbot,
      Mayette, Mellanaise, Parisienne, and Rego). Walnuts were harvested over three
      consecutive years from two different geographical origins (Braganca and Coimbra,
      Portugal), for a total of 26 samples. The methodology employed was a normal-phase
      high-performance liquid chromatography coupled to a series arrangement of a diode
      array detector followed by a fluorescence detector, allowing the simultaneous
      analysis of all tocopherols and tocotrienols. The analyses showed that all
      samples presented a similar qualitative profile composed of five compounds: alpha
      tocopherol, beta-tocopherol, gamma-tocopherol, delta-tocopherol, and gamma
      tocotrienol. gamma-Tocopherol was the major compound in all samples, ranging from
      172.6 to 262.0 mg/kg, followed by alpha- and delta-tocopherols, ranging from 8.7
      to 16.6 mg/kg and from 8.2 to 16.9 mg/kg, respectively. Multivariate analysis of
      the data obtained showed the existence of significant differences in composition
      among cultivars. These differences were also significant when cultivars were
      grouped by year of production, showing that besides genetic factors, the vitamin
      E composition was influenced by environmental factors.

PMID- 15969536
TI  - Affinity and rate constants for interactions of bovine folate-binding protein and
      folate derivatives determined by optical biosensor technology. Effect of
      stereoselectivity.
AB  - The interactions between bovine folate-binding protein (FBP) and different folate
      derivatives in pure diastereoisomeric forms were studied at pH 7.4 by a surface
      plasmon resonance technology (Biacore). The results show that folic acid had the
      most rapid association rate (k(a) = 1.0 x 10(6) M(-)(1) s(-)(1)), whereas (6S)-5
      HCO-5,6,7,8-tetrahydrofolic acid had the most rapid dissociation rate (k(d) = 3.2
      x l0(-)(3) s(-)(1)). The equilibrium dissociation constant (K(D)), calculated
      from the quotient of k(d)/k(a), showed that the two forms of folates not
      occurring in nature, that is, folic acid and (6R)-5-CH(3)-5,6,7,8-tetrahydrofolic
      acid, had the highest affinities for FBP, 20 and 160 pmol/L, respectively. The
      results thus show that there were great differences in the interactions between
      folate-binding protein and the major forms of folate derivatives. The nutritional
      implications of these differences are discussed.

PMID- 15969537
TI  - Accumulation and perchlorate exposure potential of lettuce produced in the Lower
      Colorado River region.
AB  - The Colorado River is contaminated with perchlorate concentrations of 1.5-8
      microg/L, an anion linked to thyroid dysfunction. Over 90% of the lettuce
      (Lactuca sativa L.) consumed during the winter months in the United States is
      produced in the Lower Colorado River region. Studies were conducted in this
      region to survey the potential for lettuce perchlorate accumulation and estimate
      potential human exposure to perchlorate from lettuce. Total uptake of perchlorate
      in the above-ground plant of iceberg lettuce was approximately 5 g/ha. Exposure
      estimates ranged from 0.45 to 1.8 microg/day depending on lettuce types and
      trimming. For all lettuce types, hypothetical exposures were less than 4% of the
      reference dose recommended by the National Academy of Sciences. Results show the
      relative iodide uptake inhibition potential because of lettuce nitrate was 2
      orders of magnitude greater than that associated with the corresponding trace
      levels of perchlorate. These data support the conclusion that potential
      perchlorate exposures from lettuce irrigated with Colorado River water are
      negligible relative to acute or long-term harmful amounts.

PMID- 15969538
TI  - Diastereoselective amplification of an induced-fit receptor from a dynamic
      combinatorial library.
AB  - A high-affinity, induced-fit receptor for NMe4I was discovered using dynamic
      combinatorial chemistry. The addition of the guest to a dynamic combinatorial
      library made using a racemic mixture of chiral building blocks caused the strong
      and highly diastereoselective amplification of the receptor at the expense of
      other library components. The receptor and its mode of binding were characterized
      by NMR, ITC, and re-equilibration experiments, from which it was deduced that the
      receptor probably forms a folded four-stave barrel shape on binding of the guest.

PMID- 15969539
TI  - Measuring pK(a) values in protein folding transition state ensembles by NMR
      spectroscopy.
AB  - Protein folding kinetic data have been obtained for the marginally stable N
      terminal SH3 domain of the Drosophila protein drk as a function of pH in order to
      investigate the electrostatic properties of Asp8 in the folding transition state
      ensemble. The slow exchange between folded and unfolded forms of the protein
      gives rise to separate NMR resonances for both folded and unfolded states at
      equilibrium. As a result, kinetic data can be derived from magnetization transfer
      between these two states without the need for denaturants. Using the fact that
      ionization of Asp8 dominates the electrostatic behavior of the protein between pH
      2 and 3, along with pKa values for titrating groups in both folded and unfolded
      states that have been determined in a previous study, values of 2.9 +/- 0.1 and
      3.3 +/- 0.2 are obtained for the pKa of Asp8 in the transition state for the wild
      type protein and for a His7Ala mutant, respectively. The data are consistent with
      the partial formation in the transition state ensemble of an Asp8 side chain
      carboxylate-a Lys21 backbone amide interaction that represents a highly conserved
      contact in folded SH3 domains.

PMID- 15969540
TI  - Experimental and theoretical evidence for the formation of zinc tricarbonyl in
      solid argon.
AB  - Zinc carbonyls are extremely rare. Here we report experimental and theoretical
      evidence of unprecedented zinc tricarbonyl, Zn(CO)3, the next member of the
      series of 18-electron metal carbonyls Cr(CO)6 --> Fe(CO)5 --> Ni(CO)4, whereas
      there is no evidence for the formation of the zinc mono- and dicarbonyls Zn(CO)n
      (n = 1, 2). DFT calculations predict that the Zn(CO)3 molecule has a singlet
      ground state with D3h symmetry. The formation of Zn(CO)3 involves 4s --> 4p
      promotion of the Zn atom, which increases the Zn-CO bonding by decreasing the
      sigma repulsion and significantly increasing the Zn 4sp hybrid orbitals --> CO
      pi* back-donation.

PMID- 15969541
TI  - Protein conformation-induced modulation of ligand binding kinetics: a femtosecond
      mid-IR study of nitric oxide binding trajectories in myoglobin.
AB  - By directly probing the photolyzed NO from MbNO at physiological conditions, the
      rebinding trajectories of the photoproduct were obtained, from which we found
      that a time-dependent barrier arising from protein relaxation on the same time
      scale as that of the rebinding process is responsible for the NO nonexponential
      rebinding.

PMID- 15969542
TI  - Chemoenzymatic synthesis of the polyketide macrolactone 10-deoxymethynolide.
AB  - The polyketide synthase-derived pikromycin thioesterase (Pik TE) is unique in its
      ability to catalyze the cyclization of 12- and 14-membered macrolactones. In this
      investigation, the total synthesis of the natural hexaketide chain elongation
      intermediate as its N-acetyl cysteamine (NAC) thioester has been achieved, and
      its reaction with Pik TE demonstrated the ability of Pik TE to catalyze its
      macrolactonization to the natural product 10-deoxymethynolide. A steady-state
      kinetic analysis of the hexaketide chain intermediate with Pik TE was done. A
      preliminary substrate specificity study with unnatural hexaketide analogues was
      accomplished, demonstrating the importance of total synthesis in obtaining access
      to advanced polyketide intermediates. The results show the sensitivity of Pik TE
      to minor substrate modifications, and illustrate the potential use of
      thioesterases as versatile macrolactonization catalysts.

PMID- 15969543
TI  - Using liquid crystals to report membrane proteins captured by affinity
      microcontact printing from cell lysates and membrane extracts.
AB  - The chemical heterogeneity of proteins makes development of general and facile
      surface-based methods for protein analysis a substantial challenge, particularly
      when analyzing transmembrane proteins. Here, we report a simple surface-based
      procedure that permits detection of transmembrane proteins from crude cell
      lysates and cell membrane extracts. The method relies on the use of thermotropic
      liquid crystals to amplify and report the presence of the transmembrane proteins
      captured by an affinity ligand on the surface of an elastomeric stamp. A merit of
      this approach is that the proteins can be imaged on surfaces without requiring
      the use of matched pairs of antibodies, labels, or complex instrumentation.
      Detection of epidermal growth factor receptor, a transmembrane glycoprotein, is
      demonstrated.

PMID- 15969544
TI  - Monitoring dopamine release from single living vesicles with nanoelectrodes.
AB  - Carbon fiber nanoelectrodes (tip diameter = ca. 100 nm) have been first used to
      monitor real-time dopamine release from single living vesicles of single rat
      pheochromocytoma (PC12) cells. The experiments show that active and inactive
      release sites exist on the surface of cells, and the spatial distributions have
      been differentiated even in the same active release zone. It is first
      demonstrated that multiple vesicles can sequentially release dopamine at the same
      site of the cell surface, which possibly plays the main role in the dopamine
      release from PC12 cells.

PMID- 15969545
TI  - Fabrication of uniform magnetic nanocomposite spheres with a magnetic
      core/mesoporous silica shell structure.
AB  - A novel kind of magnetic core/mesoporous silica shell nanospheres with a uniform
      particle diameter of ca. 270 nm was synthesized. The inner magnetic core endues
      the whole nanoparticle with magnetic properties, while the outer mesoporous
      silica shell shows high enough surface area and pore volume. The synthesized
      material is expected to be applied to targeted drug delivery and multiphase
      separation. The storage and release of ibuprofen into and from the pore channels
      of the mesoporous silica shell, as a typical example, are demonstrated.

PMID- 15969546
TI  - Fabrication of carbon nanotube-molecule-silicon junctions.
AB  - A hybridization strategy for the covalent connection of single wall carbon
      nanotubes to silicon surfaces via oligo(phenylene ethynylene)s has been
      demonstrated using an orthogonal bisdiazonium functionalization protocol.

PMID- 15969547
TI  - Membrane media create small nanospaces for molecular computation.
AB  - Molecular computation is fashionable because of the small device sizes that
      should be possible. For instance, information processing in nanospaces is
      widespread in biology. However, experimental cases with computing molecules
      occupy rather large volumes until now (ca. 1012 nm3). Now we demonstrate small
      scale computation using a designed logic gate in spheres of 3 nm radius (volume =
      ca. 102 nm3) which are produced by detergent micelles. The logic gate
      accommodated in the small nanospace fluoresces only when both H+ and Na+ ions are
      available.

PMID- 15969548
TI  - Full-color photochromism of a fused dithienylethene trimer.
AB  - A diarylethene fused trimer, 1-(5-(2-(3,5-dimethyl-2
      thienyl)hexafluorocyclopententen-1-yl)-2,4-dimethyl-3-thienyl)-2-(5-(2-(2,4
      dimethyl-5-phenyl-3-thienyl)hexafluorocyclopentene-1-yl)-2,4-dimethyl-3
      thienyl)hexafluorocyclopentene, was synthesized. The diarylethene derivative
      showed full-color photochromic performance by choosing appropriate wavelength of
      light.

PMID- 15969549
TI  - Redox-induced synthesis and encapsulation of metal nanoparticles in shell-cross
      linked organometallic nanotubes.
AB  - A new approach to encapsulate silver nanoparticles inside block copolymer
      nanotubes is reported and involves an in situ redox reaction between a
      polyferrocenylsilane (PFS) inner wall and silver ions. Partial preoxidation of
      the PFS domains was found to be a key step for the efficient formation of one
      dimensional arrays of silver nanoparticles confined within the nanotubes.

PMID- 15969550
TI  - Phosphaquinomethane and phosphathienoquinomethanes, and their anion radicals.
AB  - Phosphaquinomethane and phosphathienoquinomethanes sterically protected by Mes*
      (Mes* = 2,4,6-tri-tert-butylphenyl) were synthesized by 1,6-dehydration of the
      corresponding 4-phosphinoaryl carbinols. Structural similarities to the
      conventional quinoid compounds were revealed by 1H, 13C, and 31P NMR study and
      further confirmed by X-ray crystallography of the phosphathienoquinomethane. The
      corresponding anion radicals were generated by reduction with sodium, and
      considerable delocalization of an unpaired electron was demonstrated by EPR.

PMID- 15969551
TI  - Extensive quinoidal oligothiophenes with dicyanomethylene groups at terminal
      positions as highly amphoteric redox molecules.
AB  - A series of highly extensive quinoidal oligothiophenes carrying a
      dicyanomethylene group at both terminal positions is synthesized. As the
      quinoidal structures extend, they have highly amphoteric abilities and show
      strong electronic absorptions in the visible to near-infrared region. The higher
      homologues, quinquethiophene and sexithiophene, exist as equilibrium mixtures
      with the biradical species.

PMID- 15969552
TI  - Simultaneous targeted immobilization of anti-human IgG-coated nanotubes and anti
      mouse IgG-coated nanotubes on the complementary antigen-patterned surfaces via
      biological molecular recognition.
AB  - Introduction of self-assembly in nanometer-sized building blocks is expected to
      accomplish bottom-up fabrications in a more reproducible, efficient, and economic
      manner; however, it is necessary to selectively place multiple types of nano
      building blocks (e.g., metal nanotubes and semiconductor nanotubes) at specific
      locations on surfaces with high precision and reproducibility for more complex
      nanometer-scale device assemblies. Biological molecular recognition such as
      antibody-antigen bindings may be suitable to use in the building-block assembly
      since nature always assembles materials with complex functions and structures at
      room temperature reproducibly. Our approach is to immobilize antibody-coated
      nanotubes at specific complementary binding positions patterned on surfaces. To
      demonstrate this hypothesis, two types of nanotubes coated with different
      antibodies were anchored selectively onto their complementary antigen areas,
      patterned by tips of atomic force microscope (AFM). Because those nanotubes can
      be coated by various metals and semiconductors with controlled morphologies, this
      outcome opens the possibility to accomplish the proposed unconventional device
      fabrication methodology that antibody nanotubes coated with different types of
      metals/semiconductors can be self-assembled on antigen-patterned surfaces via
      biological molecular recognition.

PMID- 15969553
TI  - Block copolymer-templated chemistry on Si, Ge, InP, and GaAs surfaces.
AB  - Patterning of semiconductor surfaces is an area of intense interest, not only for
      technological applications, such as molecular electronics, sensing, cellular
      recognition, and others, but also for fundamental understanding of surface
      reactivity, general control over surface properties, and development of new
      surface reactivity. In this communication, we describe the use of self-assembling
      block copolymers to direct semiconductor surface chemistry in a spatially defined
      manner, on the nanoscale. The proof-of-principle class of reactions evaluated
      here is galvanic displacement, in which a metal ion, M+, is reduced to M0 by the
      semiconductor, including Si, Ge, InP, and GaAs. The block copolymer chosen has a
      polypyridine block which binds to the metal ions and brings them into close
      proximity with the surface, at which point they undergo reaction; the pattern of
      resulting surface chemistry, therefore, mirrors the nanoscale structure of the
      parent block copolymer. This chemistry has the added advantage of forming metal
      nanostructures that result in an alloy or intermetallic at the interface, leading
      to strongly bound metal nanoparticles that may have interesting electronic
      properties. This approach has been shown to be very general, functioning on a
      variety of semiconductor substrates for both silver and gold deposition, and is
      being extended to organic and inorganic reactions on a variety of conducting,
      semiconducting, and insulating substrates.

PMID- 15969554
TI  - Photorelease of alcohols from 2-nitrobenzyl ethers proceeds via hemiacetals and
      may be further retarded by buffers intercepting the primary aci-nitro
      intermediates.
AB  - The mechanism for the photoinduced release of glycolic acid from its 2
      nitrobenzyl ether was reinvestigated. The pH-dependent rate constants of the
      thermal reactions initiated by irradiation are similar to those reported
      previously for 2-nitrobenzyl methyl ether. A hemiacetal intermediate that limits
      the release rate of glycolic acid at pH values </=7 was identified by time
      resolved IR and UV measurements. Furthermore, 2-(2'-nitrosophenyl)-1,3-dioxolan-4
      one, a long-lived intermediate formed by intramolecular trapping of the aci
      tautomer, was observed and characterized.

PMID- 15969555
TI  - Supramolecular nano networks formed by molecular-recognition-directed self
      assembly of ditopic calix[5]arene and dumbbell [60]fullerene.
AB  - Dumbbell fullerene 1 and ditopic bisdouble-calix[5]arene 2 were synthesized.
      Their iterative host-guest complexations create the supramolecular nano network.
      Scanning electron microscopy revealed the formation of the branched fiber,
      possessing a length of more than 100 mum and widths of 250-500 nm on a glass
      plate. More detailed information was given by atomic force microscopy. The formed
      fibers on a mica plate have widths of 60-90 nm and heights of 1.2-1.9 nm. The
      nanosize assemblies are probably composed of a bundle of 40-60 polymer chains
      created by entangling the alkyl side chains with van der Waals interaction.

PMID- 15969556
TI  - Functional oligo(vinyl acetate) CO2-philes for solubilization and emulsification.
AB  - The development of inexpensive and biodegradable CO2-soluble ligands,
      surfactants, and phase transfer agents is an important goal in the implementation
      of supercritical fluid technology. We report here a potentially generic synthetic
      route to inexpensive oligo(vinyl acetate) CO2-philes for applications such as
      solubilization and emulsification. These materials are shown to outperform more
      expensive fluorinated surfactants in particular applications.

PMID- 15969557
TI  - A homochiral porous metal-organic framework for highly enantioselective
      heterogeneous asymmetric catalysis.
AB  - A homochiral porous noninterpenetrating metal-organic framework (MOF), 1, was
      constructed by linking infinite 1D [Cd(mu-Cl)2]n zigzag chains with axially
      chiral bipyridine bridging ligands containing orthogonal secondary functional
      groups. The secondary chiral dihydroxy groups accessible via the large open
      channels in 1 were utilized to generate a heterogeneous asymmetric catalyst for
      the addition of diethyzinc to aromatic aldehydes to afford chiral secondary
      alcohols at up to 93% enantiomeric excess (ee). Control experiments with
      dendritic aromatic aldehydes of different sizes indicate that the heterogeneous
      asymmetric catalyst derived from 1 is both highly active and enantioselective as
      a result of the creation of readily accessible, uniform active catalyst sites
      inside the porous MOF.

PMID- 15969558
TI  - Enantioselective Friedel-Crafts alkylations of alpha,beta-unsaturated 2-acyl
      imidazoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes.
AB  - An enantioselective Friedel-Crafts alkylation with alpha,beta-unsaturated 2-acyl
      imidazoles and electron-rich aromatic nucleophiles catalyzed by
      bis(oxazolinyl)pyridine-scandium(III) triflate complexes has been accomplished.
      These alpha,beta-unsaturated 2-acyl imidazoles are effective electrophiles for
      the Friedel-Crafts reaction. The resulting adduct 2-acyl imidazole is easily
      converted to amides, esters, carboxylic acids, ketones, and aldehydes by
      methylation and subsequent displacement of the imidazole residue.

PMID- 15969559
TI  - Exceptionally facile CO addition to a saturated ruthenium complex.
AB  - Synthesis and characterization of Cp*Ru[eta3-HC(PPh2NPh)2], 1, reveals it to have
      a "piano stool" structure with the ligand bound to Ru(II) via two N and the
      unique, sp3 hybridized carbon. While the analogous (cymene) Ru[eta3
      HC(PPh2NPh)2]+ does not react with CO, under the same conditions, 1 adds one CO
      rapidly (25 degrees C, 1 atm CO). Characterization, including an X-ray structure
      determination, shows that CO has displaced one chelate ligand nitrogen, which
      then hangs off the molecule, free of Ru. DFT calculations reveal a possible
      mechanism via a remarkably low energy (+9.3 kcal/mol) intermediate, pendant N,
      but with one phenyl on phosphorus stabilizing Ru via donation from a
      C(ipso)=C(ortho) bond. DFT calculations show that the electronic energy change
      for binding CO is over 20 kcal/mol less favorable for cymene than for C5Me5- as
      ligand; the reactivity difference is thus thermodynamic in origin.

PMID- 15969560
TI  - Acylation versus sulfonylation in the inhibition of elastase by 3-oxo-beta
      sultams.
AB  - beta-Sultams are the sulfonyl analogues of beta-lactams, and 3-oxo-beta-sultams
      are both beta-lactams and beta-sultams and, therefore, susceptible to
      nucleophilic attack at either the acyl or the sulfonyl center. They are novel
      inactivators of serine enzymes. The second-order rate constant for the
      inactivation of elastase at pH 6 by N-benzyl-4,4-dimethyl-3-oxo-beta-sultam is
      768 M-1 s-1, which is 103-fold greater than that with N-benzoyl beta-sultam.
      However, in contrast to N-acyl beta-sultams, which sulfonylate the active site
      serine residue to form a sulfonate ester, 3-oxo-beta-sultams inhibit the enzyme
      by acylation followed by slow deacylation to regenerate the active enzyme.

PMID- 15969561
TI  - Catalytic enantioselective C-C bond forming conjugate additions with vinyl
      sulfones.
AB  - In this communication, we describe the development of the first highly
      enantioselective catalytic conjugate addition to vinyl sulfones. Promoted by
      readily accessible organocatalysts derived from C6'-OH cinchona alkaloid
      derivatives and under mild, air- and moisture-tolerant conditions, conjugate
      additions of a wide range of alpha-cyanoacetates bearing either an alpha-aryl or
      an alpha-alkyl substituent to vinyl sulfones proceeded in excellent
      enantioselectivity and high yield. Consequently, this efficient and operationally
      simple enantioselective C-C bond forming conjugate addition provides a new and
      useful approach for the enantioselective construction of all-carbon quaternary
      stereocenters.

PMID- 15969562
TI  - Dithiolato-bridged dinuclear iron-nickel complexes [Fe(CO)2(CN)2(mu
      SCH2CH2CH2S)Ni(S2CNR2)]- modeling the active site of [NiFe] hydrogenase.
AB  - [NiFe] hydrogenase, the enzyme of which catalyzes the reversible oxidation of
      molecular hydrogen to protons and electrons, contains a unique heterodinuclear
      thiolate-bridged Ni-Fe complex in which the iron center is coordinated by CO and
      CN. We have synthesized dithiolate-bridged Ni-Fe complexes bearing CO and CN
      ligands to model the active center of [NiFe] hydrogenase. The Ni-Fe complexes
      containing a [(CN)2(CO)2Fe(mu-S2)NiS2] framework are the closest yet structural
      models of [NiFe] hydrogenase.

PMID- 15969563
TI  - A low-threshold, high-efficiency microfluidic waveguide laser.
AB  - This communication describes a long (1 cm), laser-pumped, liquid core-liquid
      cladding (L2) waveguide laser. This device provides a simple, high intensity,
      tunable light source for microfludic applications. Using a core solution of 2 mM
      rhodamine 640 perchlorate, optically pumped by a frequency-doubled Nd:YAG laser,
      we found that the threshold for lasing was as low as 22 muJ (16-ns pulse length)
      and had a slope efficiency up to 20%. The output wavelength was tunable over a 20
      nm range by changing the ratio of solvent components (dimethyl sulfoxide and
      methanol) in the liquid core.

PMID- 15969564
TI  - Quantification of singlet oxygen production in the reaction of superoxide with
      hydrogen peroxide using a selective chemiluminescent probe.
AB  - A sensitive chemiluminescent probe that selectively reacts with singlet oxygen in
      the presence of superoxide and hydrogen peroxide has been used to quantify the
      production of singlet oxygen in the reaction of superoxide with hydrogen
      peroxide. The yield of singlet oxygen from this reaction was found to be low
      (0.2% relative to the initial superoxide concentration). No evidence for the
      formation of hydroxyl radical was observed in this reaction, ruling out the Haber
      Weiss mechanism as a major singlet oxygen formation pathway. No singlet oxygen
      production was observed in the reaction of superoxide with 2-nitrobenzoic acid,
      which has a pKa similar to that of hydrogen peroxide, rendering the protonation
      of superoxide, followed by its disproportionation, an unlikely explanation for
      the formation of singlet oxygen in this system. The low yields of singlet oxygen
      and hydroxyl radical suggest that their formation in this reaction should be
      relatively unimportant in biological systems.

PMID- 15969565
TI  - The template synthesis of double coaxial carbon nanotubes with nitrogen-doped and
      boron-doped multiwalls.
AB  - We present the first synthesis of double coaxial carbon nanotubes with nitrogen
      doped and boron-doped multiwalls by the template technique with two-step chemical
      vapor deposition. X-ray photoelectron spectra confirm the coaxial formation of
      different-doped structures. The electrical conductance and oxygen chemisorption
      measurement indicate dual electrical properties and chemical activity at their
      outer and inner layers.

PMID- 15969566
TI  - Fluorous bulk membranes for potentiometric sensors with wide selectivity ranges:
      observation of exceptionally strong ion pair formation.
AB  - Potentiometric sensors based on fluorous membranes doped with a fluorophilic
      tetraphenylborate derivative are shown to have a remarkably wide range of
      selectivities that exceeds the selectivity range of conventional polymeric
      membranes by 8 orders of magnitude. The fluorous character of these sensing
      membranes explains the formation of ion pairs of unprecedented strength. Ion pair
      formation constants in perfluoroperhydrophenanthrene, as measured in this work,
      are on the order of 1020 and exceed previously reported values for ion pair
      formation in nonpolar solvents by 6 orders of magnitude. The low solubility of
      lipids in such fluorous phases makes them very promising for the reduction of
      biofouling.

PMID- 15969567
TI  - Concurrent cyclopropanation by carbenes and carbanions.
AB  - The generation of phenylhalocarbenes in the presence of varying quantities of
      halide ions and electron-poor alkenes affords concurrent cyclopropanation of the
      alkenes by an equilibrating mixture of phenylhalocarbenes and phenylhalomethide
      carbanions, which permits the smooth modulation of selectivity between electron
      poor alkenes and electron-rich alkenes, a feature of potential synthetic utility.

PMID- 15969568
TI  - Catalytic asymmetric epoxidation of alpha,beta-unsaturated esters using an
      yttrium-biphenyldiol complex.
AB  - We succeeded in a catalytic asymmetric epoxidation reaction of alpha,beta
      unsaturated esters via a conjugate addition of an oxidant using 2-10 mol % of the
      yttirium-chiral biphenyldiol catalyst. A variety of substrates with beta-aryl and
      beta-alkyl substituents were epoxidized efficiently, yielding the corresponding
      alpha,beta-epoxy esters in up to 97% yield and 99% ee.

PMID- 15969570
TI  - Catalytic asymmetric hydrogenation of N-iminopyridinium ylides: expedient
      approach to enantioenriched substituted piperidine derivatives.
AB  - We have developed an efficient catalytic enantioselective hydrogenation of
      pyridine derivatives. Enhanced reactivity was possible by an optimization of the
      electronic properties of the catalyst through ligand modification. This
      methodology shows the particular reactivity of N-iminopyridinium ylides that
      provides access to substituted piperidines in good enantiomeric excesses.

PMID- 15969569
TI  - Thiourea-catalyzed enantioselective cyanosilylation of ketones.
AB  - The new chiral amino thiourea catalyst 3d promotes the highly enantioselective
      cyanosilylation of a wide variety of ketones. The hindered tertiary amine
      substituent plays a crucial role with regard to both stereoinduction and
      reactivity, suggesting a cooperative mechanism involving electrophile activation
      by thiourea and nucleophile activation by the amine.

PMID- 15969571
TI  - Light-controlled molecular switches modulate nanocrystal fluorescence.
AB  - Spiropyran dyes were attached to fluorescent core-shell CdSe/ZnS nanocrystals via
      thiol-containing linkers. Photoisomerization of the dye to its merocyanine form
      by UV irradiation caused a dramatic loss in the intrinsic nanoparticle
      fluorescence, which was regained upon reversing the isomerization with visible
      light. The fluorescence quenching efficiency increased with increasing spectral
      overlap of fluorescence emission and merocyanine adsorption bands, consistent
      with FRET as the quenching mechanism. Typically, complete quenching required at
      least 80 bound dye molecules per particle.

PMID- 15969572
TI  - Total synthesis of RK-397.
AB  - An enantioselective synthesis of the polyene macrolide RK-397 is described. The
      use of the same eight-carbon building block twice for the construction of the
      polyol chain allowed for a highly convergent synthesis. The synthesis highlights
      stereoselective vinylogous aldol addition using a chiral bisphosphoramide as well
      as a sequential palladium-catalyzed cross-coupling reaction for the preparation
      of key fragments.

PMID- 15969573
TI  - An efficient, stereocontrolled synthesis of a potent omuralide-salinosporin
      hybrid for selective proteasome inhibition.
AB  - A short and highly stereocontrolled synthesis of the potent proteasome inhibitor
      3 from the (S)-threonine-derived oxazoline 4 has been developed. The synthetic
      sequence is summarized in Scheme 1. Aldol coupling of the zinc enolate of 4 with
      isobutyraldehyde and subsequent silylation provided the TBS ether 5
      diastereoselectively (10:1). Reductive cleavage of the oxazoline ring of 5
      followed by Swern oxidation of the resulting amino alcohol afforded amino ketone
      6, converted further by N-acylation to the acrylamide 7, whose structure was
      confirmed by X-ray crystallographic analysis. Acrylamide 7 was cyclized to 8 by a
      novel application of the Kulinkovich Ti(II)-cyclopentene complex. Silylation of 8
      to 9 and radical cyclization at low temperature produced the bicyclic lactam 10
      with complete control of all stereocenters. Hydroxy desilylation and N
      deprotection of 10 gave the dihydroxy ester 11, which was converted to 3 by a
      novel three-step sequence: (1) demethylation with [Me2AlTeMe]2, (2) combined beta
      lactonization and chlorination, and (3) desilylation to effect cleavage of the
      TBS ether.

PMID- 15969574
TI  - Evidence for the isomerization and decarboxylation in the photoconversion of the
      red fluorescent protein DsRed.
AB  - Recently, it has been shown that the red fluorescent protein DsRed undergoes
      photoconversion on intense irradiation, but the mechanism of the conversion has
      not yet been elucidated. Upon irradiation with a nanosecond-pulsed laser at 532
      nm, the chromophore of DsRed absorbing at 559 nm and emitting at 583 nm (R form)
      converts into a super red (SR) form absorbing at 574 nm and emitting at 595 nm.
      This conversion leads to a significant change in the fluorescence quantum yield
      from 0.7 to 0.01. Here we demonstrate that the photoconversion is the result of
      structural changes of the chromophore and one amino acid. Absorption,
      fluorescence, and vibrational spectroscopy as well as mass spectrometry suggest
      that a cis-to-trans isomerization of the chromophore and decarboxylation of a
      glutamate (E215) take place upon irradiation to form SR. At the same time,
      another photoproduct (B) with an absorption maximum at 386 nm appears upon
      irradiation. This species is assigned as a protonated form of the DsRed
      chromophore. It might be a mixture of several protonated DsRed forms as there is
      at least two ways of formation. Furthermore, the photoconversion of DsRed is
      proven to occur through a consecutive two-photon absorption process. Our results
      demonstrate the importance of the chromophore conformation in the ground state on
      the brightness of the protein as well as the importance of the photon flux to
      control/avoid the photoconversion process.

PMID- 15969575
TI  - Long-range magnetic ordering in iron jarosites prepared by redox-based
      hydrothermal methods.
AB  - The iron jarosites, plumbojarosite, Pb0.5Fe3(OH)6(SO4)2, argentojarosite,
      AgFe3(OH)6(SO4)2, and thallium jarosite, TlFe3(OH)6(SO4)2, along with the
      selenate-capped jarosite analogues of potassium, KFe3(OH)6(SeO4)2, and rubidium,
      RbFe3(OH)6(SeO4)2, have been prepared in their analytically pure forms by
      employing redox-based hydrothermal methods. The crystal structures of these
      materials have been determined, and all are found to be essentially isostructrual
      including Pb0.5Fe3(OH)6(SO4)2, which is distinct from the structure reported for
      naturally mined samples. All iron jarosites show long-range order (LRO),
      signified by a sharp transition temperature, T(N), which falls in the narrow
      temperature range of 61.4 +/- 5 K. The mechanism responsible for this ordering
      has been established by examining magnetostructural correlations for the
      jarosites possessing various interlayer cation and capping groups. We show that
      all magnetic properties of jarosites, including LRO, find their origin in the
      basic magnetic unit, the intralayer Fe3(mu-OH)3 triangle. Field-dependent
      magnetization experiments are consistent with the antiferromagnetic stacking of
      an out of plane moment developed from spin canting within Fe3(mu-OH)3 triangles.
      Together with the previously reported AFe3(OH)6(SO4)2 (A = Na+, K+, Rb+ and NH4+)
      jarosites, these compounds provide a framework for probing magnetic ordering in a
      spin frustrated lattice of the largest series of isoelectronic and isostructural
      kagome systems yet discovered.

PMID- 15969576
TI  - Columnar mesomorphic organizations in cyclotriphosphazenes.
AB  - A synthetic strategy has been developed to prepare cyclotriphosphazenes that bear
      polycatenar aromatic esters as promesogenic units linked to phosphorus atoms. The
      microsegregation of the rigid and flexible parts of the system and the space
      filling properties are the driving forces that determine the kind of mesomorphism
      exhibited by the organocyclotriphosphazenes. Mesogenic units that contain only
      one terminal alkyl chain give rise to calamitic mesomorphism, since the molecules
      are arranged to give a cylindrical superstructure with the aromatic promesogenic
      cores elongated in a manner approximately perpendicular to the
      cyclotriphosphazene ring. On the other hand, mesogenic units that contain three
      long terminal chains exhibit columnar mesophases. In this case, a discotic
      structure consisting of promesogenic cores arranged approximately parallel to the
      cyclotriphosphazene ring can explain the columnar organization. The X-ray
      diffraction patterns corresponding to the Col(h) mesophase of the
      cyclotriphosphazene with dodecyloxy chains (8) indicate the presence of helical
      ordering, which was confirmed for a homologous compound bearing stereogenic
      centers on two of the terminal chains (11). All of the synthesized phosphazenes
      show a high thermal stability.

PMID- 15969577
TI  - Vanadium-based, extended catalytic lifetime catechol dioxygenases: evidence for a
      common catalyst.
AB  - In 1999, a catechol dioxygenase derived from a V-polyoxometalate was reported
      which was able to perform a record >100 000 total turnovers of 3,5-di-tert
      butylcatechol oxygenation using O2 as the oxidant (Weiner, H.; Finke, R. G. J.
      Am. Chem. Soc. 1999, 121, 9831). An important goal is to better understand this
      and other vanadium-based catechol dioxygenases. Scrutiny of 11 literature reports
      of vanadium-based catechol dioxygenases yielded the insight that they all proceed
      with closely similar selectivities. This, in turn, led to a "common catalyst
      hypothesis" for the broad range of vanadium based catechol dioxygenase
      precatalysts presently known. The following three classes of V-based compounds,
      10 complexes total, have been explored to test the common catalyst hypothesis:
      (i) six vanadium-based polyoxometalate precatalysts, (n-Bu4N)4H5PV14O42, (n
      Bu4N)7SiW9V3O40, (n-Bu4N)5[(CH3CN)(x)Fe(II).SiW9V3O40], (n-Bu4N)9P2W15V3O62, (n
      Bu4N)5Na2[(CH3CN)(x)Fe(II).P2W15V3O62], and (n-Bu4N)4H2-gamma-SiW10V2O40; (ii)
      three vanadium catecholate complexes, [V(V)O(DBSQ)(DTBC)]2,
      [Et3NH]2[V(IV)O(DBTC)2].2CH3OH, and [Na(CH3OH)2]2[V(V)(DTBC)3]2.4CH3OH (where
      DBSQ = 3,5-di-tert-butylsemiquinone anion and DTBC = 3,5-di-tert-butylcatecholate
      dianion), and (iii) simple VO(acac)2. Product selectivity studies, catalytic
      lifetime tests, electron paramagnetic resonance spectroscopy (EPR), negative ion
      mode electrospray ionization-mass spectrometry (negative ion ESI-MS), and kinetic
      studies provided compelling evidence for a common catalyst or catalyst resting
      state, namely, Pierpont's structurally characterized vanadyl semiquinone
      catecholate dimer complex, [VO(DBSQ)(DTBC)]2, formed from V-leaching from the
      precatalysts. The results provide a considerable simplification and unification
      of a previously disparate literature of V-based catechol dioxygenases.

PMID- 15969578
TI  - Stable hydrocarbon diradical, an analogue of trimethylenemethane.
AB  - Hydrocarbon diradical 1, a new stable, 3-fold symmetric analogue of
      trimethylenemethane (TMM) with no heteroatom perturbation, is prepared and
      studied. Such diradicals should provide new building blocks for high-spin
      hydrocarbon polyradicals with very strong net ferromagnetic coupling. Magnetic
      studies (SQUID) and EPR spectroscopy indicate that 1 in tetrahydrofuran-d8 (THF
      d8) possesses a triplet (S = 1) ground state, with strong ferromagnetic coupling.
      After annealing at room temperature, the EPR spectra of 1 (approximately 0.02 M
      in frozen THF-d8) consist of a single narrow resonance (deltaH(pp) < 1 G), and
      intermolecular antiferromagnetic coupling is increased by 1 order of magnitude.
      This behavior is consistent with the presence of exchange narrowing, thus
      suggesting aggregation of 1 in THF-d8. Blue solutions of 1 in THF-d8 possess a
      strong UV-vis absorption band at lambda(max) approximately 640 nm. Diradical 1 in
      THF-d8 is stable (or persistent) at room temperature, with no detectable
      decomposition for at least 2 days.

PMID- 15969579
TI  - Electron affinities of 1,1-diaryl-2,3,4,5-tetraphenylsiloles: direct measurements
      and comparison with experimental and theoretical estimates.
AB  - We present a comprehensive experimental and theoretical characterization of the
      electronic structure of four 1,1-diaryl-2,3,4,5-tetraphenylsiloles (aryl =
      phenyl, 2-(9,9-dimethylfluorenyl), 2-thienyl, pentafluorophenyl). Solid-state
      electron affinities and ionization potentials of these siloles were measured
      using inverse-photoelectron spectroscopy (IPES) and photoelectron spectroscopy
      (PES), respectively; the density of electronic states obtained from calculations
      performed at the density functional theory (DFT) level corresponds very well to
      the PES and IPES data. The direct IPES measurements of electron affinity were
      then used to assess alternative estimates based on electrochemical and/or optical
      data. We also used DFT to calculate the reorganization energies for the electron
      transfer reactions between these siloles and their radical anions. Additionally,
      optical data and ionization potential and electron affinity data were utilized to
      estimate the binding energies of excitons in these siloles.

PMID- 15969580
TI  - Single-crystal studies of peptide prolyl and glycyl 15N shielding tensors.
AB  - 15N shielding tensors were determined for the central peptide groups in GGV, AGG,
      and APG by single-crystal NMR. We find that the angle between the downfield
      component (delta11) and the N-H or the N-C(delta) (pro) bonds is in the range of
      20-23 degrees and in accord with previous solid-state NMR measurements. However,
      AGG, unlike APG or GGV, has a distorted peptide plane, and delta11 lies
      approximately in the plane of N, C(alpha), and H rather than in the peptide plane
      defined by heavy atoms. Accurate orientations of delta22 and delta33 were
      determined, and the usual assumption that delta22 is along the peptide normal was
      found only in APG which has a highly nonaxial tensor. More generally, delta22 and
      delta33 are rotated about the delta11 axis (36 degrees in GGV). These results are
      compared with DFT calculations to gain a structural understanding of the effects
      of intermolecular interactions on shielding tensor principal components and
      orientations. Trimeric clusters containing H-bonded neighbors predict the
      orientations of the principal components within 2-3 degrees, but calculated
      principal components are less quantitative. Possible reasons for this
      disagreement are explored.

PMID- 15969581
TI  - Modulation of calcium oxalate monohydrate crystallization by citrate through
      selective binding to atomic steps.
AB  - The majority of human kidney stones are composed primarily of calcium oxalate
      monohydrate (COM) crystals. Thus, determining the molecular modulation of COM
      crystallization by urinary constituents is crucial for understanding and
      controlling renal stone disease. A comprehensive molecular-scale view of COM
      shape modification by citrate, obtained through a combination of in situ atomic
      force microscopy and molecular modeling, is presented here. We find that while
      the most important factors determining binding strength are coordination between
      COO- groups on citrate and Ca ions in the lattice, as well as H-bonds formed
      between the OH group of citrate and an oxalate group, the nonplanar geometry of
      the steps provides the most favorable environment due to the ability of the step
      edge to accommodate all Ca-COO- coordinations with minimal strain. However,
      binding to all steps and terraces on the (010) face is much less favorable than
      on the (101) face due to electrostatic repulsion between oxalate and COO- groups.
      For example, the maximum binding energy, -166.5 kJ mol(-1), occurs for the [101]
      step on the (101) face, while the value for the [021] step on the (010) face is
      only -56.9 kJ mol(-1). This high selectivity leads to preferential binding to
      steps on the (101) face that pins step motion. Yet anisotropy in interaction
      strength on this face drives anisotropic changes in step kinetics that are
      responsible for shape modification of macroscopic COM crystals. Thus, the
      molecular scale growth kinetics and the bulk crystal habit are fully consistent
      with the simulations.

PMID- 15969582
TI  - Molecular recognition of carbohydrates with artificial receptors: mimicking the
      binding motifs found in the crystal structures of protein-carbohydrate complexes.
AB  - The binding motifs found in the crystal structures of protein-carbohydrate
      complexes have been successfully mimicked with simple acyclic pyridine- and
      pyrimidine-based receptors. A full discussion of the recognition motifs observed
      in the crystal structures of complexes of receptors 1 and 3 with glucopyranosides
      4a and 4b is provided. A remarkable similarity of these motifs to those observed
      in the crystal structures of sugar-binding proteins and those found by molecular
      modeling is shown. In addition, the recognition properties of the new pyrimidine
      receptor 3 toward monosaccharides 4-6 are described. This molecule has been
      established as a highly effective receptor for beta-glucopyranosides.

PMID- 15969583
TI  - Smectic liquid crystals from supramolecular guanidinium alkanesulfonates.
AB  - The thermotropic polymorphism of a series of guanidinium alkanesulfonates (6 < or
      = n < or = 18) was investigated by optical microscopy and differential scanning
      calorimetry. Hydrogen bonding was analyzed by infrared spectroscopy. Molecular
      volumes were measured by dilatometry. The structure of the crystal, smectic A,
      and ordered smectic phases observed were studied by X-ray diffraction and
      utilized to prove that the supramolecular arrangement of the molecules in the
      crystal survives in the smectic phases at high temperature.

PMID- 15969584
TI  - Effect of tip functionalization on transport through vertically oriented carbon
      nanotube membranes.
AB  - Ionic flux through a composite membrane structure, containing vertically aligned
      carbon nanotubes crossing a polystyrene matrix film, was studied as a function of
      chemical end groups at the entrance to carbon nanotubes' (CNTs) cores. Plasma
      oxidation during the membrane fabrication process introduced carboxylic acid
      groups on the CNTs' tips that were modified using carbodiimide mediated coupling
      between the carboxylic acid and an accessible amine groups of the functional
      molecule. Functionalization molecules included straight chain alkanes,
      anionically charged dye molecules, and an aliphatic amine elongated by
      polypeptide spacers. Functionalization was confirmed by FTIR spectroscopy, and
      areal functional density was estimated by transmission electron microscopy
      studies of thiol terminated sites decorated by nanocrystalline gold. The
      transport through the membrane of two different sized but equally charged
      molecules (ruthenium bipyridine [Ru-(bipy)3(2+)] and methyl viologen [MV2+]) was
      quantified in a U-tube permeation cell by UV-vis spectroscopy. Relative
      selectivity of the permeates varied from 1.7 to 3.6 as a function of tip
      functionalization chemistry. Anionic charged functional groups sharply increased
      the flux of the cationic permeates. This effect was reduced at higher solution
      ionic strength consistent with shorter Debye screening length. The observed
      selectivities were consistent with a hindered diffusion model with
      functionalization at the CNT tip and not along the length of the CNT core.

PMID- 15969585
TI  - Highly fluorescent solid-state asymmetric spirosilabifluorene derivatives.
AB  - A series of four asymmetrically aryl-substituted 9,9'-spiro-9-silabifluorene
      (SSF) derivatives, 2,2'-di-tert-butyl-7,7'-diphenyl-9,9'-spiro-9-silabifluorene
      (PhSSF), 2,2'-di-tert-butyl-7,7'-dipyridin-2-yl-9,9'-spiro-9-silabifluorene
      (PySSF), 2,2'-di-tert-butyl-7,7'-dibiphenyl-4-yl-9,9'-spiro-9-silabifluorene
      (BPhSSF), and 2,2'-di-tert-butyl-7,7'-bis(2',2' '-bipyridin-6-yl)-9,9'-spiro-9
      silabifluorene (BPySSF) are prepared through the cyclization of the corresponding
      2,2'-dilithiobiphenyls with silicon tetrachloride. These novel spiro-linked
      silacyclopentadienes (siloles) form transparent and stable amorphous films with
      relatively high glass transition temperatures (T(g) = 203-228 degrees C). The
      absorbance spectrum of each compound shows a significant bathochromic shift
      relative to that of the corresponding carbon analogue as a result of the
      effective sigma-pi conjugation between the sigma orbital of the exocyclic Si-C
      bond and the pi orbital of the oligoarylene fragment. Solid-state films exhibit
      intense violet-blue emission (lambda(PL) = 398-415 nm) with high absolute
      photoluminescence quantum yields (phi(PL) = 30-55%).

PMID- 15969586
TI  - Single-component catalyst/initiators for the organocatalytic ring-opening
      polymerization of lactide.
AB  - The synthesis and characterization of a series of primary and secondary alcohol
      adducts of 1,3-dimesitylimidazolin-2-ylidene is described. These adducts are
      stable as solids at room temperature, but readily release alcohol and the free
      carbene in solution. These alcohol adducts function as excellent single-component
      catalyst/initiators for the ring-opening polymerization of lactide under mild
      conditions, providing polymers with controlled molecular weights and narrow
      polydispersities. Multifunctional adducts were used to prepare poly(lactide)s of
      more complex architectures.

PMID- 15969587
TI  - G-matrix Fourier transform NOESY-based protocol for high-quality protein
      structure determination.
AB  - A protocol for high-quality structure determination based on G-matrix Fourier
      transform (GFT) NMR is presented. Five through-bond chemical shift correlation
      experiments providing 4D and 5D spectral information at high digital resolution
      are performed for resonance assignment. These are combined with a newly
      implemented (4,3)D GFT NOESY experiment which encodes information of 4D 15N/15N-,
      13C(alipahtic)/15N-, and 13C(aliphatic)/13C(aliphatic)-resolved [1H,1H]-NOESY in
      two subspectra, each containing one component of chemical shift doublets arising
      from 4D --> 3D projection at omega1:Omega(1H) +/- Omega(X) [X =
      15N,13C(aliphatic)]. The peaks located at the centers of the doublets are
      obtained from simultaneous 3D 15N/13C(aliphatic)/13C(aromatic)-resolved [1H,1H]
      NOESY, wherein NOEs detected on aromatic protons are also obtained. The protocol
      was applied for determining a high-quality structure of the 14 kDa Northeast
      Structural Genomics consortium target protein, YqfB (PDB ID ). Through-bond
      correlation and NOESY spectra were acquired, respectively, in 16.9 and 39 h (30 h
      for shift doublets, 9 h for central peaks) on a 600 MHz spectrometer equipped
      with a cryogenic probe. The rapidly collected highly resolved 4D NOESY
      information allows one to assign the majority of NOEs directly from chemical
      shifts, which yields accurate initial structures "within" approximately 2
      angstroms of the final structure. Information theoretical "QUEEN" analysis of
      initial distance limit constraint networks revealed that, in contrast to
      structure-based protocols, such NOE assignment is not biased toward identifying
      additional constraints that tend to be redundant with respect to the available
      constraint network. The protocol enables rapid NMR data collection for robust
      high-quality structure determination of proteins up to approximately 20-25 kDa in
      high-throughput.

PMID- 15969588
TI  - Photo-cross-linked immobilization of polyelectrolytes for enzymatic construction
      of conductive nanocomposites.
AB  - Horseradish peroxidase has been demonstrated to catalyze the oxidative
      polymerization of aniline to form conductive polyaniline. This process is
      facilitated by the presence of a macromolecular template with sulfonic acid
      groups that provide a unique environment for the formation of the conducting
      polymer. Here we report the use of a photo-cross-linkable thymine-based polymer
      with phenylsulfonate groups as a templating substrate. This allows for an aqueous
      based environmentally benign photopatterning of a conductive material. A
      description and results of this process are presented.

PMID- 15969589
TI  - Polaron delocalization in ladder macromolecular systems.
AB  - Organic macromolecules with conjugated building blocks have been the focus of
      extensive research that is motivated, in part, by the potential to create optical
      and electronic devices. We have shown that palladium-catalyzed amination can
      assemble triarylamine ladder materials with extended structures. Two ladder
      macromolecules have been prepared in high yields by a series of twelve or sixteen
      C-N coupling reactions. Studies of the electronic and optical properties of
      neutral and oxidized forms of the ladder structures were conducted. The optical
      and electronic properties of the ladder systems are compared to those of the
      linear tetra-phenyl-p-phenylenediamine as well as the tetra-p-anisyl-p
      tetraazacyclophane. The electrochemistry of the ladder systems consists of a
      multiwave voltammogram with a relatively low first oxidation potential. Electron
      paramagnetic resonance spectroscopy of the ladder systems suggests the presence
      of a large density of delocalized polarons. Linear absorption measurements of the
      chemically oxidized ladders revealed both polaron and intervalence absorption
      bands. Steady-state and time-resolved fluorescence measurements were also carried
      out to characterize the dynamics in these novel systems.

PMID- 15969590
TI  - How the Co-C bond is cleaved in coenzyme B12 enzymes: a theoretical study.
AB  - The homolytic cleavage of the organometallic Co-C bond in vitamin B12-dependent
      enzymes is accelerated by a factor of approximately 10(12) in the protein
      compared to that of the isolated cofactor in aqueous solution. To understand this
      much debated effect, we have studied the Co-C bond cleavage in the enzyme
      glutamate mutase with combined quantum and molecular mechanics methods. We show
      that the calculated bond dissociation energy (BDE) of the Co-C bond in adenosyl
      cobalamin is reduced by 135 kJ/mol in the enzyme. This catalytic effect can be
      divided into four terms. First, the adenosine radical is kept within 4.2
      angstroms of the Co ion in the enzyme, which decreases the BDE by 20 kJ/mol.
      Second, the surrounding enzyme stabilizes the dissociated state by 42 kJ/mol
      using electrostatic and van der Waals interactions. Third, the protein itself is
      stabilized by 11 kJ/mol in the dissociated state. Finally, the coenzyme is
      geometrically distorted by the protein, and this distortion is 61 kJ/mol larger
      in the Co(III) state. This deformation of the coenzyme is caused mainly by steric
      interactions, and it is especially the ribose moiety and the Co-C5'-C4' angle
      that are distorted. Without the polar ribose group, the catalytic effect is much
      smaller, e.g. only 42 kJ/mol for methyl cobalamin. The deformation of the
      coenzyme is caused mainly by the substrate, a side chain of the coenzyme itself,
      and a few residues around the adenosine part of the coenzyme.

PMID- 15969591
TI  - A luminescence sensor of inositol 1,4,5-triphosphate and its model compound by
      ruthenium-templated assembly of a bis(Zn2+-cyclen) complex having a 2,2'
      bipyridyl linker (cyclen = 1,4,7,10-tetraazacyclododecane).
AB  - A new supramolecular complex (Ru(Zn2L4)3) was designed and synthesized as a
      luminescence sensor for inositol 1,4,5-triphosphate (IP3), which is one of the
      important second messengers in intracellular signal transduction, and its achiral
      model compound, cis,cis-1,3,5-cyclohexanetriol triphosphate (CTP3), by a
      ruthenium(II)-templated assembly of three molecules of a bis(Zn2+-cyclen) complex
      having a 2,2-bipyridyl linker (Zn2L4). Single-crystal X-ray diffraction analysis
      of a racemic mixture of Ru(Zn2L4)3 showed that three of the six Zn2+-cyclen units
      are orientated to face the opposite side of the molecule with three apical
      ligands (Zn2+-bound HO-) of each of the three Zn2+ located on the same face. 1H
      NMR and UV titrations of Ru(Zn2L4)3 with CTP3 indicated that Ru(Zn2L4)3 forms a
      1:2 complex with CTP3, (Ru(Zn2L4)3)-((CTP3)6-)2, in aqueous solution at neutral
      pH. In the absence of guest molecules, Ru(Zn2L4)3 (10 microM) has an emission
      maximum at 610 nm at pH 7.4 (10 mM HEPES with I = 0.1 (NaNO3)) and 25 degrees C
      (excitation at 300 nm). An addition of 2 equiv of CTP3 induced a 4.2-fold
      enhancement in the emission of Ru(Zn2L4)3 at 584 nm. In this article, we describe
      that Ru(Zn2L4)3 is the first chemical sensor that directly responds to CTP3 and
      IP3 and discriminates these triphosphates from monophosphates and diphosphates.
      The photodecomposition of Ru(Zn2L4)3, which is inhibited upon complexation with
      CTP3, and the stereoselective complexation of chiral IP3 by Ru(Zn2L4)3 are also
      described.

PMID- 15969592
TI  - Powder crystallography by proton solid-state NMR spectroscopy.
AB  - The investigation of 1H-1H spin-diffusion build-up curves using a rate matrix
      analysis approach shows that high-resolution magic angle spinning NMR of protons,
      applied to powdered organic compounds, provides a method to probe crystalline
      arrangements. The comparison between experimental 1H data and simulation is shown
      to depend strongly on the parameters of the crystal structure, for example on the
      unit cell parameters or the orientation of the molecule in the unit cell, and
      those parameters are experimentally determined for a model organic compound.

PMID- 15969593
TI  - The role of the peripheral anionic site and cation-pi interactions in the ligand
      penetration of the human AChE gorge.
AB  - We study the ligand (tetramethylammonium) recognition by the peripheral anionic
      site and its penetration of the human AChE gorge by using atomistic molecular
      dynamics simulations and our recently developed metadynamics method. The role of
      both the peripheral anionic site and the formation of cation-pi interactions in
      the ligand entrance are clearly shown. In particular, a simulation with the W286A
      mutant shows the fundamental role of this residue in anchoring the ligand at the
      peripheral anionic site of the enzyme and in positioning it prior to the gorge
      entrance. Once the ligand is properly oriented, the formation of specific and
      synchronized cation-pi interactions with W86, F295, and Y341 enables the gorge
      penetration. Eventually, the ligand is stabilized in a free energy basin by means
      of cation-pi interactions with W86.

PMID- 15969594
TI  - Synthesis, physical properties, multitemperature crystal structure, and 20 K
      synchrotron X-ray charge density of a magnetic metal organic framework structure,
      Mn3(C8O4H4)3(C5H11ON)2.
AB  - A new magnetic metal organic framework material has been synthesized,
      Mn3(C8O4H4)3(C5H11ON)2, 1. Magnetic susceptibility measurements from 2 to 400 K
      reveal anti-ferromagnetic ordering at approximately 4 K and a total magnetic
      moment of 6.0 micro(B). The magnetic phase transition is confirmed by heat
      capacity data (2-300 K). The crystal structure is studied by conventional single
      crystal X-ray diffraction data at 300, 275, 250, 225, 200, 175, 150, 125, and 100
      K, and synchrotron data at 20 K. There is a phase transition between 100 and 20 K
      due to ordering of the diethylformamide molecules. The X-ray charge density is
      determined based on multipole modeling of a second 20 K single-crystal
      synchrotron radiation data set. The electron distributions around the two unique
      Mn centers are different, and both have substantial anisotropy. Orbital
      population analysis reveals large electron donation (1.7 e) to each Mn atom and
      the maximum possible number of unpaired electrons is 3.2 for both Mn sites. Thus,
      there is a considerable orbital component to the magnetic moment. Bader
      topological analysis shows an absence of Mn-Mn bonding, and the magnetic ordering
      is via super-exchange through the oxygen bridges. Formal electron counting
      suggests Mn2+ sites, but this is not supported by the Bader atomic charges, Mn1 =
      +0.11 e, Mn2 = +0.17 e. The topological measures show the dominant metal-ligand
      interactions to be electrostatic, and a simple exponential correlation is derived
      between Mn-O bond lengths and the values of nabla2rho at the bond critical
      points.

PMID- 15969595
TI  - Conservation of mus-ms enzyme motions in the apo- and substrate-mimicked state.
AB  - Solution NMR spin-relaxation experiments were used to compare mus-ms dynamics in
      RNase A in the apo form and as complexed to the substrate-mimic, pTppAp. The
      crystal structure of the RNase A/pTppAp complex was determined and demonstrates
      that this ligand binds at the active site and utilizes established substrate
      binding sites in its interaction with RNase A. Relaxation-compensated CPMG
      experiments identify flexible residues in and around the active site in both the
      apo and pTppAp-bound enzyme. Quantitative analysis of the NMR spin-relaxation
      dispersion curves show that the time scale of motion in RNase A is unchanged when
      pTppAp binds and is similar to the time scale for the rate-determining step of
      the catalytic reaction. Temperature-dependent measurements provide an activation
      barrier for motion of 5.2 +/- 1.0 kcal/mol and 4.5 +/- 1.2 kcal/mol for the apo
      and pTppAp forms of RNase A, respectively. These data indicate very similar
      motion exists in the free and bound enzyme. Additionally, chemical shift data
      suggests that the magnitude of motion is also similar for these two forms and
      that it is likely that apo enzyme interconverts to a structure that resembles a
      ligand-bound form. Likewise, it appears that the bound conformation samples the
      apo enzyme form even when ligand is present. Taken together the data imply that
      RNase A is in a preexisting dynamic equilibrium between two conformations that
      represent the open and closed enzyme forms. These data suggest that ligand
      binding stabilizes the bound conformer but does not induce it.

PMID- 15969596
TI  - Nanostructuring, compositional fluctuations, and atomic ordering in the
      thermoelectric materials AgPb(m)SbTe(2+m). The myth of solid solutions.
AB  - The nature of the thermoelectric materials Ag(1-x)Pb(m)SbTe(m+2) or LAST-m
      materials (LAST for Lead Antimony Silver Tellurium) with different m values at
      the atomic as well as nanoscale was studied with powder/single-crystal X-ray
      diffraction, electron diffraction, and high-resolution transmission electron
      microscopy. Powder diffraction patterns of different members (m = 0, 6, 12, 18,
      infinity) are consistent with pure phases crystallizing in the NaCl-structure
      type (Fmm) and the proposition that the LAST family behaved as solid solutions
      between the PbTe and AgSbTe2 compounds. However, electron diffraction and high
      resolution transmission electron microscopy studies suggest the LAST phases are
      inhomogeneous at the nanoscale with at least two coexisting sets of well-defined
      phases. The minority phase which is richer in Ag and Sb is on the nanosized
      length scale, and it is endotaxially embedded in the majority phase which is
      poorer in Ag and Sb. Moreover, within each nanodomain we observe extensive long
      range ordering of Ag, Pb, and Sb atoms. The long range ordering can be confirmed
      by single crystal X-ray diffraction studies. Indeed, data collections of five
      different single crystals were successfully refined in space groups of lower
      symmetry than Fmm including P4/mmm and Rm. The results reported here provide
      experimental evidence for a conceptual basis that could be employed when
      designing high performance thermoelectric materials and dispel the decades long
      belief that the systems (AgSbTe2)(1-x)(PbTe)x are solid solutions.

PMID- 15969597
TI  - Magnetoswitchable reactions of DNA monolayers on electrodes: gating the processes
      by hydrophobic magnetic nanoparticles.
AB  - Biorecognition and biocatalytic reactions of DNA monolayers, such as
      hybridization, polymerization, and hydrolytic digestion, were followed in situ by
      chronocoulometry and Faradaic impedance spectroscopy. Hydrophobic magnetic
      nanoparticles attracted to, and retracted from, the electrode surface by an
      external magnetic field were used to activate and inhibit the DNA-monolayer
      reactions, respectively. The attraction of the magnetic nanoparticles to the
      electrode surface generated a hydrophobic thin film on the surface that is not
      permeable for the water-soluble components required for the DNA-monolayer
      reactions. This results in the inhibition of the DNA-monolayer reactions. The
      retraction of the magnetic nanoparticles from the surface regenerated the free
      nucleic acid-functionalized surface that was exposed to the aqueous solution,
      thus reactivating the DNA-monolayer reactions. The reversible inhibition and
      activation of the DNA-monolayer reactions upon the cyclic attraction-retraction
      of the hydrophobic magnetic nanoparticles may be used to synthesize programmed
      DNA chips.

PMID- 15969598
TI  - Synthesis and reaction of [[HC(CMeNAr)2]Mn]2 (Ar = 2,6-iPr2C6H3): the complex
      containing three-coordinate manganese(I) with a Mn-Mn bond exhibiting unusual
      magnetic properties and electronic structure.
AB  - This paper reports on the synthesis, X-ray structure, magnetic properties, and
      DFT calculations of [[HC(CMeNAr)2]Mn]2 (Ar = 2,6-iPr2C6H3) (2), the first complex
      with three-coordinate manganese(I). Reduction of the iodide [[HC(CMeNAr)2]Mn(mu
      I)]2 (1) with Na/K in toluene afforded 2 as dark-red crystals. The molecule of 2
      contains a Mn2(2+) core with a Mn-Mn bond. The magnetic investigations show a
      rare example of a high-spin manganese(I) complex with an antiferromagnetic
      interaction between the two Mn(I) centers. The DFT calculations indicate a strong
      s-s interaction of the two Mn(I) ions with the open shell configuration (3d54s1).
      This suggests that the magnetic behavior of 2 could be correctly described as the
      coupling between two S1 = S2 = 5/2 spin centers. The Mn-Mn bond energy is
      estimated at 44 kcal mol(-1) by first principle calculations with the B3LYP
      functional. The further oxidative reaction of 2 with KMnO4 or O2 resulted in the
      formation of manganese(III) oxide [[HC(CMeNAr)2]Mn(mu-O)]2 (3). Compound 3 shows
      an antiferromagnetic coupling between the two oxo-bridged manganese(III) centers
      by magnetic measurements.

PMID- 15969599
TI  - Coordination-based gold nanoparticle layers.
AB  - Gold nanoparticle (NP) mono- and multilayers were constructed on gold surfaces
      using coordination chemistry. Hydrophilic Au NPs (6.4 nm average core diameter),
      capped with a monolayer of 6-mercaptohexanol, were modified by partial
      substitution of bishydroxamic acid disulfide ligand molecules into their capping
      layer. A monolayer of the ligand-modified Au NPs was assembled via coordination
      with Zr4+ ions onto a semitransparent Au substrate (15 nm Au, evaporated on
      silanized glass and annealed) precoated with a self-assembled monolayer of the
      bishydroxamate disulfide ligand. Layer-by-layer construction of NP multilayers
      was achieved by alternate binding of Zr4+ ions and ligand-modified NPs onto the
      first NP layer. Characterization by atomic force microscopy (AFM), ellipsometry,
      wettability, transmission UV-vis spectroscopy, and cross-sectional transmission
      electron microscopy showed regular growth of NP layers, with a similar NP density
      in successive layers and gradually increased roughness. The use of coordination
      chemistry enables convenient step-by-step assembly of different ligand-possessing
      components to obtain elaborate structures. This is demonstrated by introducing
      nanometer-scale vertical spacing between a NP layer and the gold surface, using a
      coordination-based organic multilayer. Electrical characterization of the NP
      films was carried out using conductive AFM, emphasizing the barrier properties of
      the organic spacer multilayer. The results exhibit the potential of coordination
      self-assembly in achieving highly controlled composite nanostructures comprising
      molecules, NPs, and other ligand-derivatized components.

PMID- 15969600
TI  - "Concerted" transition state, stepwise mechanism. Dynamics effects in C2-C6 enyne
      allene cyclizations.
AB  - The C2-C6 (Schmittel)/ene cyclization of enyne-allenes is studied by a
      combination of kinetic isotope effects, theoretical calculations, and dynamics
      trajectories. For the cyclization of allenol acetate 9, the isotope effect
      (k(CH3)/k(CD3) is approximately 1.43. The isotope effect is interpreted in terms
      of a highly asynchronous transition state near the concerted/stepwise boundary.
      This is supported by density functional theory calculations that locate a highly
      asynchronous transition structure for the concerted ene reaction. However,
      calculations of both the experimental system and a model reaction were unable to
      locate a transition structure for formation of the diradical intermediate of a
      stepwise mechanism. The stepwise mechanism and the asynchronous concerted
      mechanism start out geometrically similar, and the two pathways appear to have
      merged as far as the initial transition structure. For the model reaction,
      quasiclassical direct dynamics trajectories emanating from the initial transition
      structure afforded the diradical intermediate in 29 out of 101 trajectories. A
      large portion of the remaining trajectories completes hydrogen transfer before
      carbon-carbon bond formation, despite the advanced carbon-carbon bond formation
      in the asynchronous transition structure. Overall, the single minimum-energy path
      from starting material to product is inadequate to describe the reaction, and a
      consideration of dynamic effects is necessary to understand the mechanism. The
      implications of these observations toward questions of concert in other reactions
      are discussed.

PMID- 15969601
TI  - Effect of molecular weight on the exponential growth and morphology of
      hyaluronan/chitosan multilayers: a surface plasmon resonance spectroscopy and
      atomic force microscopy investigation.
AB  - The layer-by-layer growth of multilayer assemblies of two polysaccharides, the
      polyanion hyaluronan (HA) and the polycation chitosan (CH), was investigated
      using atomic force microscopy (AFM) and surface plasmon resonance (SPR)
      spectroscopy, with primary emphasis on the effect of the polysaccharide molecular
      weights on the film thickness and surface morphology. The HA/CH multilayers
      exhibit an exponential increase of the optical film thickness with the number of
      deposited bilayers. We show that the multilayer thickness at a given stage
      depends on the size of both CH, the diffusing polyelectrolyte, and HA, the non
      diffusing species. Assemblies (12 bilayers) of high molecular weight
      polysaccharides (HA, 360,000; CH, 160,000) were twice as thick (approximately 900
      nm vs approximately 450 nm) as those obtained with low molecular weight polymers
      (HA, 30,000; CH, 31,000), as assessed by AFM scratch tests. The exponential
      growth rate is the same for the high and low molecular weight pairs; the larger
      film thicknesses observed by SPR and by AFM arising from an earlier onset of the
      steep exponential growth phase in the case of the high molecular weight pair. In
      all cases, isolated islets form during the deposition of the first CH layer onto
      the underlying HA. Upon further film growth, individual islets coalesce into
      larger vermiculate features. The transition from distinct islands to vermiculate
      structures depends on the molecular weights of the polysaccharides and the lower
      molecular weight construct presents larger worm-like surface domains than the
      high molecular weight pair.

PMID- 15969602
TI  - Electrochemical gate-controlled conductance of single oligo(phenylene
      ethynylene)s.
AB  - We have studied electron transport properties of unsubstituted oligo(phenylene
      ethynylene) (OPE) (1) and nitro-substituted OPE (2) covalently bound to two gold
      electrodes. The conductance values of single 1 and 2 are approximately 13 and
      approximately 6 nS, respectively. In addition to a decrease in the conductance,
      the presence of the nitro moiety leads to asymmetric I-V characteristics and a
      negative differential resistance-like (NDR-like) behavior. We have altered the
      nitro-substituted OPE by electrochemically reducing the nitro group and by
      varying the pH of the electrolyte. The conductance decreases linearly with the
      electron-withdrawing capability (i.e., Hammett substituent values) of the
      corresponding reduced species. In contrast, the conductance of 1 is independent
      of the pH and the electrode potential.

PMID- 15969603
TI  - Theoretical prediction of noble gas containing anions FNgO- (Ng = He, Ar, and
      Kr).
AB  - The structures and energies of the noble gas containing anions FNgO- (Ng = He,
      Ar, and Kr) have been calculated by high-level ab initio calculations. The FNgO-
      anions were found to be deep-energy minima at the singlet electronic state, and
      their energies are significantly lower than those at the triplet state. High
      dissociation energy barriers to Ng + OF- were also predicted. The unexpected
      stability of the FNgO- was due to the dramatic ion-induced O=Ng bond formation.
      The calculated results suggested possible experimental identification of the
      anionic species and even some related "ionic compounds" under cryogenic
      conditions.

PMID- 15969604
TI  - Total synthesis of brevetoxin B.
AB  - The convergent total synthesis of brevetoxin B (1) has been achieved. The
      intramolecular allylation of the O,S-acetal 20, prepared from the alpha
      chlorosulfide 17 and the alcohol 5, was carried out using AgOTf as a Lewis acid
      to give the diene 21, predominantly. Ring-closing metathesis of 21 with the
      Grubbs catalyst 23 afforded the hexacyclic ether 25 which was converted to the A
      G ring segment 2 through several steps. The intramolecular allylation of the
      alpha-acetoxy ether 42, prepared from 2 and the J-K ring segment 3, followed by
      ring-closing metathesis provided the polycyclic ether framework 44. A series of
      reactions of 44, including oxidation of the A ring, deprotection of the silyl
      ethers, and selective oxidation of the resulting allylic alcohol, furnished 1.

PMID- 15969605
TI  - Highly active, immobilized ruthenium catalysts for oxidation of alcohols to
      aldehydes and ketones. Preparation and use in both batch and flow systems.
AB  - A novel, highly active immobilized ruthenium catalyst, which can be successfully
      used in oxidation of alcohols to aldehydes and ketones, has been developed. In
      contrast to most immobilized catalysts, the Ru catalyst has activity that is
      higher than that of the original non-immobilized catalyst. In a batch system, the
      Ru catalyst was recovered and reused several times without loss of activity. The
      catalyst was also applied to a flow system, in which excellent conversions and
      yields were demonstrated. No leaching of Ru was observed in both cases.

PMID- 15969606
TI  - A 13C NMR study of the molecular dynamics and phase transition of confined
      benzene inside titanate nanotubes.
AB  - This work investigated the nanoconfinement effect on the molecular dynamics and
      phase transition of confined benzene inside titanate nanotubes with a uniform
      inner diameter of approximately 5.3 nm. For 13C-enriched organics, the 13C
      nuclear spin-spin relaxation was demonstrated as a sensitive tool to
      differentiate molecular translational motion and reorientation and, thus, was
      shown to be advantageous over the commonly employed 1H and 2H NMR for studying
      complex phase diagram, specifically, for separating the phase behavior of
      translational motion and the phase behavior of molecular reorientation. In such
      an approach, the melting of translational motion of confined benzene was
      explicitly observed to take place in a broad temperature range below the bulk
      melting temperature. The abrupt change of the 13C nuclear spin-spin relaxation
      time of the confined liquid benzene at about 260 K suggested that nanoconfinement
      induced two topologically distinct liquid phases.

PMID- 15969607
TI  - Copper- or phosphine-catalyzed reaction of alkynes with isocyanides.
      Regioselective synthesis of substituted pyrroles controlled by the catalyst.
AB  - The copper-catalyzed reaction of isocyanides (CNCH2EWG1) 1 with electron
      deficient alkynes (RC[triple bond]CEWG2) 2 gave the 2,4-di-EWG-substituted
      pyrroles 3 selectively, whereas the phosphine-catalyzed reaction of 1 with 2
      afforded the 2,3-di-EWG-subsituted pyrroles 4. Accordingly, regioselective
      synthesis of substituted pyrroles has been achieved by merely choosing the
      catalyst.

PMID- 15969608
TI  - Enhancement of O2 dissociation on Au111 by adsorbed oxygen: implications for
      oxidation catalysis.
AB  - We show that the dissociation probability of O2 on the reconstructed, Au111
      herringbone surface is dramatically increased by the presence of some atomic
      oxygen on the surface. Specifically, at 400 K the dissociation probability of O2
      on oxygen precovered Au111 is on the order of 10(-3), whereas there is no
      measurable dissociation on clean Au111, establishing an upper bound for the
      dissociation probability of 10(-6). Atomic oxygen was deposited on the clean
      reconstructed Au111-herringbone surface using electron bombardment of condensed
      NO2 at 100 K. The dissociation probability for dioxygen was measured by exposing
      the surface to 18O2. Temperature programmed desorption (TPD) was used to quantify
      the amount of oxygen dissociation and to study the stability of the oxygen in all
      cases. Oxygen desorbs as O2 in a peak centered at 550 K with pseudo-first-order
      kinetics; i.e., the desorption peak does not shift with coverage. Our
      interpretation is that the coverage dependence of the activation energy for
      dissociation (deltaE(dis)) and/or preexponential factor (nu(d)) may be
      responsible for the unusual desorption kinetics, implying a possible energy
      barrier for O2 dissociation on Au111. These results are discussed in the context
      of Au oxidation chemistry and the relationship to supported Au nanoparticles.

PMID- 15969609
TI  - Efficient preparation of organic substrate-RNA conjugates via in vitro
      transcription.
AB  - A concise synthetic way has been developed for the preparation of guanosine
      monophosphate derivatives carrying a decaethylene glycol spacer at their 5'
      oxygen to which are attached a range of organic substrates. The four different
      compounds, prepared via a convergent synthetic strategy, carry a tethered
      benzylallyl ether residue (1a), an anthracene (1b), a benzyl carbamate residue
      (1c), or a primary amino group (1d), respectively. All four compounds have been
      successfully incorporated at the 5'-end of a 25-mer long RNA transcript via T7
      RNA polymerase, and no inhibition of chain elongation could be observed. Under
      proper conditions, 1a and 1b can be incorporated up to 90-95% and 1c up to 68%.
      The amino-terminated initiator 1d is incorporated less efficiently although still
      up to 49%. These results show that the more hydrophobic the guanosine
      monophosphate derivative is, the higher is its enzymatic incorporation.

PMID- 15969610
TI  - Selective solvent interactions in a fluorous reaction system.
AB  - Mixtures of chloroform and perfluoro(methylcyclohexane) can be used as solvents
      for "fluorous" biphase reactions since they exist as two separate phases at low
      temperature but become a single phase at higher temperatures. Intermolecular
      nuclear Overhauser effects have been used to investigate the interactions of
      solvent components with the protons and fluorines of 3-heptafluorobutyrylcamphor
      in both phases of this biphasic system at 25 degrees C as well as the single
      phase at 54 degrees C. The results indicate that at 25 degrees C in the
      perfluorocarbon-rich phase, both solvent components interact with the solute
      selectively. There are no indications of unusual solute interactions of either
      solvent component in the chloroform-rich phase and only weak suggestions of
      selective interactions in the high-temperature phase. Various mechanisms for the
      enhancement of solute spin-solvent spin cross relaxation rates in the
      perfluoro(methylcyclohexane)-rich phase are considered. It is suggested that the
      solvation layer around the solute has a composition and possibly hydrodynamic
      properties different from those of the bulk solution in this phase. There are
      indications of appreciable regioselectivity of chloroform interactions with the
      hydrocarbon part of the solute in all phases.

PMID- 15969611
TI  - A highly efficient organocatalyst for direct aldol reactions of ketones with
      aldehydes [corrected].
AB  - L-proline amides derived from various chiral beta-amino alcohols that bear
      substituents with various electron natures at their stereogenic centers are
      prepared and evaluated for catalyzing the direct Aldol reaction of 4
      nitrobenzaldehyde with acetone. Catalysts with strong electron-withdrawing groups
      are found to exhibit higher catalytic activity and enantioselectivity than their
      analogues with electron-donating groups. The presence of 2 mol % catalyst 4g
      significantly catalyzes the direct Aldol reactions of a wide range of aldehydes
      with acetone and butanone, to give the beta-hydroxy ketones with very high
      enantioselectivities ranging from 96% to >99% ee. High diastereoselectivity of
      95/5 was observed for the anti Aldol product from the reaction of cyclohexanone,
      and excellent enantioselectivity of 93% ee was provided for anti Aldol product
      from the reaction of cyclopentanone.

PMID- 15969612
TI  - Kinetic acidity of aliphatic hydrocarbons. Hydrogen isotope exchange with cesium
      cyclohexylamide in cyclohexylamine.
AB  - Kinetic acidities are reported for methane, ethane, propane, cyclopropane,
      isobutane, neopentane, tetramethylbutane, norbornane, nortricyclene, and
      adamantane by tritiodeprotonation or deuteriodeprotonation in cyclohexylamine
      catalyzed by cesium cyclohexylamide.

PMID- 15969615
TI  - Unimolecular photochemistry of 4-thiouracils.
AB  - Unimolecular phototautomeric reactions in 4-thiouracil, 1-methyl-4-thiouracil and
      6-aza-4-thiouracil were studied using the matrix-isolation technique combined
      with infrared absorption spectroscopy. For monomers of these compounds, isolated
      in solid argon at 10 K, an intramolecular proton-transfer photoreaction was
      observed. Upon UV (lambda > 345 nm) irradiation, the initial oxo-thione forms of
      4-thiouracils were converted into the corresponding oxo-thiol tautomers. The
      photogenerated oxo-thiol isomers were identified by comparing their experimental
      IR spectra with the spectra theoretically calculated at the DFT(B3LYP)/6
      311++G(2d,p) level. Good agreement between the observed and predicted pattern of
      spectral bands allowed a reliable identification. This is the first report on
      experimental observation of isomeric forms of 4-thiouracils other than the
      canonical oxo-thione tautomers.

PMID- 15969613
TI  - Computational characterization of the role of the base in the Suzuki-Miyaura
      cross-coupling reaction.
AB  - The role of the base in the transmetalation step of the Suzuki-Miyaura cross
      coupling reaction is analyzed computationally by means of DFT calculations with
      the Becke3LYP functional. The model system studied consists of Pd(CH=CH2)(PH3)2Br
      as the starting catalyst complex, CH2=CHB(OH)2 as the organoboronic acid, and OH-
      as the base. The two main mechanistic proposals, consisting of the base attacking
      first either the palladium complex or the organoboronic acid, are evaluated
      through geometry optimization of the corresponding intermediates and transition
      states. Supplementary calculations are carried out on the uncatalyzed reaction
      and on a process where the starting complex is Pd(CH=CH2)(PH3)2(OH). These
      calculations, considered together with available experimental data, strongly
      suggest that the main mechanism of transmetalation in the catalytic cycle starts
      with the reaction of the base and the organoboronic acid.

PMID- 15969616
TI  - Temperature effects, arrhenius activation parameters and rate constants for the
      photochemical reactivity of cyano, boronato, trifluoromethyl and methoxy
      substituted toluenes in the excited singlet state.
AB  - Total rate constants of decay (k(t)) as a function of temperature from -45 to +65
      degrees C for the compounds 1 and 2 in AN and TFE and 3 and 4 in AN have been
      determined by fluorescence lifetime measurements. The data have been fit to an
      equation that assumes that the rate constants of fluorescence (k(f)) and
      intersystem crossing (k(isc)) are temperature independent, that k(ic) = 0 and
      that the rate constant of reaction (k(r)) is activated according to the Arrhenius
      expression. For compounds 1-3, values of k(f) and k(isc) were found to be
      independent of solvent for any given compound, but k(r) was consistently greater
      in TFE than AN. For the anisoles 4, the temperature effect was very small,
      indicating that k(r) did not compete with k(f) + k(isc) and suggesting that an
      activated intersystem crossing was the dominant temperature-dependent process.
      The k(r), A and E(a) values obtained for compounds 1-3 were rationalized in terms
      of their known photochemistry, phototransposition reactions in AN and
      photoadditions in TFE. The critical reactive intermediate in all cases is a
      bicycle[3.1.0]hexenyl biradical/zwitterion that is formed in an activated process
      from S1. This reactive intermediate returns to starting material faster than it
      rearranges, and therefore an activated internal conversion is a major pathway for
      deactivation of S1.

PMID- 15969617
TI  - Endothelial progenitor cells from cord blood: a new therapeutic promise?

PMID- 15969618
TI  - Evolutionary, biological origins of morality: implications for research with
      human embryonic stem cells.
AB  - Medical research with human embryonic stem cells, despite its enormous potential
      to reduce human suffering, is banned in many countries and heavily restricted in
      others. "Moral reasons" are invoked to justify bans and restrictions on this
      promising research. Rather surprisingly, while those moral reasons have been
      extensively discussed and hotly debated in several papers, not a single article
      on the moral aspects of that research has attempted to answer this fundamental
      question: What is morality? Considering that a scientifically objective
      definition of morality is essential to determine whether those moral reasons are
      justified or groundless, this article focuses on the evolutionary origins of
      morality and its biological basis. Morality arose as a selectively advantageous
      product of evolution and preceded all religions and philosophies by millions of
      years. For the 99% of humankind's evolution, morality was axiomatically aimed at
      reducing the sufferings of the social members, because pains and afflictions, as
      expressions of diseases and impairments, tended to hasten the extinction of the
      small ancestral groups, which characteristically consisted of a few tens of
      members. Had the therapeutic use of human embryos been available in remote times,
      our ancestors would have deemed it unquestionably immoral to save amorphous and
      microscopic agglomerates of insensitive cells representing neither parental nor
      social investment, at the expense of the lives of the suffering members of their
      little communities. Unless we venture the untenable thesis that the unlikelihood
      of extinction of our immense societies entitles us to overturn the meaning of
      morality, we cannot but conclude that bans and restrictions on research with
      human embryonic stem cells are patently immoral.

PMID- 15969619
TI  - MAP kinase: a switch in fate determination of stem cells.

PMID- 15969620
TI  - Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft.
AB  - Herein we review recent data that support host tolerance of allogeneic adult
      mesenchymal stem cells (MSC). Evidence is emerging that donor MSC deploy a very
      powerful array of mechanisms that allow escape from host allogeneic responses.
      These mechanisms include limited expression of alloantigen by the stem cell and
      cell contact-dependent and -independent mechanisms. MSC modulate host dendritic
      cell and T cell function, promoting induction of suppressor or regulatory T
      cells. These effects are complemented by the induction of divisional arrest
      anergy in T cells and by stem cell production of soluble immunomodulatory
      factors, including interleukin-10, transforming growth factor-beta, prostaglandin
      E2, and hepatocyte growth factor. In addition, MSC express the enzyme indoleamine
      2,3-dioxygenase, which creates a tryptophan-depleted milieu that promotes
      immunosuppression. We propose that these observations show striking similarity to
      emerging data on the maternal acceptance of the fetal allograft. This comparison
      suggests new approaches to determine the contribution of different mechanisms to
      the successful use of MSC in regenerative medicine.

PMID- 15969621
TI  - Human motor neuron differentiation from human embryonic stem cells.
AB  - The therapeutic potential of embryonic stem (ES) cells is promising, but in many
      cases limited by our inability to promote their differentiation to specific cell
      types, such as motor neurons. Here we provide the first report of the successful
      differentiation of human ES cells to cells of a motor neuron phenotype. A
      renewable source of neuroepithelial cells was generated from human ES cells.
      Extracellular signals were then employed to induce motor neuron differentiation
      and related gene expression by these cells. OLIG2 and HLXB9 gene expression
      increased upon the addition of basic fibroblast growth factor, retinoic acid, and
      sonic hedgehog, as a motor neuron phenotype expressing Islet1 and choline
      acetyltransferase (ChAT) developed. This study demonstrates that neuroepithelial
      cells derived from human ES cells are renewable progenitors capable of generating
      motor neurons at levels that may be therapeutically useful. Sonic hedgehog, basic
      fibroblast growth factor, and retinoic acid differentially influence human motor
      neuron differentiation by mechanisms that remain to be defined.

PMID- 15969622
TI  - Development of a focused microarray to assess human embryonic stem cell
      differentiation.
AB  - Human embryonic stem cells (hESC) must be differentiated before clinical use. In
      addition, the extent of contamination of undifferentiated cells and the
      efficiency of differentiation must also be assessed prior to clinical
      application. In this manuscript, we describe the development of a focused
      microarray that may be used to discriminate between hESC and their differentiated
      progeny. This array contains 755 genes including embryonic stem cell markers as
      well as markers of differentiation into neural, mesodermal, and endodermal
      phenotypes. In addition, we have included candidate genes belonging to families
      of cytokines, chemokines, receptors, signaling pathways, and homeodomain proteins
      that are likely to be important in the process of differentiation. Testing and
      validation of the focused array was performed using RNA from hESC, human embryoid
      body (hEB) outgrowths, and a human embryonal carcinoma (hEC) cell line. We have
      compared gene expression with negative background, GAPDH, beta-actin positive
      controls, and human universal RNA (hURNA), showing that such an array can rapidly
      distinguish between undifferentiated and differentiated hESC-derived cell
      populations. We expect that the described array will be extremely useful in
      evaluating the extent of differentiation and the state of the hESC-derived
      population utilized for therapeutic purposes.

PMID- 15969623
TI  - Small intestinal organoid-derived SP cells contribute to repair of irradiation
      induced skin injury.
AB  - Side population (SP) cells, characterized by their ability to efflux the
      fluorescent dye Hoechst 33342, were isolated from the small intestine of mice. In
      the abdominal irradiation model, small intestinal organoid-derived SP (sioSP)
      cells from ROSA 26 mice were submucosally injected into the small intestinal of
      the irradiated C57BL/6 mice. In contrast to the control mice, mice receiving
      sioSP cell transplantation demonstrated far less skin injury. Most importantly,
      hairs in the irradiated body part of the transplanted mice almost remained black,
      whereas the counterpart in the control mice almost turned white. Histochemistry
      studies showed the donor cells gave rise to skin cells in the irradiated skin.
      Thus, our study demonstrated for the first time that stem cells from the small
      intestine can differentiate into skin cells under local cues and thus supports
      the theory of stem cell plasticity.

PMID- 15969624
TI  - Correlation between melanoma angiogenesis and the mesenchymal stem cells and
      endothelial progenitor cells derived from bone marrow.
AB  - Endothelial progenitor cells (EPC) reportedly differentiate into endothelial
      cells and participate in angiogenesis, including neovascularization at sites of
      neoplastic development. Recently, we reported that Flk+/CD31-/CD34- mesenchymal
      stem cells (MSC) possess the potential of differentiating into both endothelial
      and hematopoietic cells. We hypothesized that these MSC contribute to tumor
      angiogenesis. This concept is controversial and this study was undertaken to
      address this controversy. We show that progeny of human MSC as well as
      differentiated endothelial cells possess the ability to participate in tumor
      angiogenesis. When human marrow-derived MSC were injected into tail veins of
      severe combined immunodeficient (SCID) mice engrafted with human malignant
      melanoma, human cells incorporated into tumor vessels. Moreover, human-derived
      endothelial cells were identified in the walls of mouse tumor vessels by
      immunohistology. We report for the first time that similar results are obtained
      when mice carrying malignant melanoma are injected with differentiated human
      endothelial cells. Thus, we demonstrate that both differentiated endothelial
      cells from tissue peripheral to that of a tumor as well as progeny of human MSC
      have similar capacities to participate in angiogenesis.

PMID- 15969625
TI  - Reduction of myocardial scar size after implantation of mesenchymal stem cells in
      rats: what is the mechanism?
AB  - The use of a cellular therapy offers a promising approach for the treatment of
      heart disease. Besides other precursor cells, bone marrow (BM)-derived stem cells
      were discovered that migrate into ischemic myocardium and participate in
      myogenesis as well as angiogenesis. A subpopulation of those are the mesenchymal
      stem cells (MSC), which may be potential candidates for repairing ischemic heart
      tissue. MSC are easy to prepare and can be used in an autologous strategy. Here
      we demonstrate the effect of transplanted MSC in our autologous rat model of
      myocardial injury. BM was isolated from tibiae and femurs of Wistar rats. After
      24 h, the adhering MSC were separated, expanded, retrovirally transduced using
      green fluorescent protein (GFP), and cloned. A cryo-infarct was generated in the
      rat hearts, and immediately after this the cells were injected into the border
      zone of the lesion. After a 10-week follow up, the hearts were excised and the
      myocardial scar areas were measured using computer-guided morphometry. When
      comparing transplanted rats (n = 8) with control animals (n = 5) treated rats
      demonstrated a significant reduction in the width (p < 0.05) of the myocardial
      scar area. The depth of the scars of the cell therapy rats was less extended (p >
      0.05) and the myocardium of these animals was thicker than in the controls (p >
      0.05). Immunohistochemical analyses revealed neither evidence of MSC
      transdifferentiation into cardiomyocytes, nor could an increased
      neovascularization be found. In conclusion, MSC are responsible for a remarkable
      reduction of the myocardial scar size in the treated animals. But, whether this
      strategy is directly transferable to the patient suffering from heart disease has
      to be determined. In addition, the mechanism by which MSC act in the ischemic
      heart remains to be determined.

PMID- 15969626
TI  - CD4+ CD25+ lymphocyte and dendritic cell mobilization with intermediate doses of
      recombinant human granulocyte colony-stimulating factor in healthy donors.
AB  - We prospectively conducted a quantitative and phenotypic analysis of T, B,
      natural killer (NK), NKT, type 1 and 2 dendritic cells (DC), and regulatory T
      cells, before and after mobilization with intermediate doses of granulocyte
      colony-stimulating factor (G-CSF) (16 microg/kg per day). Between November, 2003,
      and December, 2004, we collected stem cells from 25 HLA identical sibling donors
      for allogeneic hematopoietic stem cell transplantation. Before mobilization and 3
      h after the fourth and fifth doses of G-CSF, blood samples were taken for blood
      counts and flow cytometry. The median number of regulatory T cells before and
      after G-CSF was statistically different (69 +/- 41 x 10(6)/L versus 161 +/- 159 x
      10(6)/L, p < 0.01). We observed a 1.7-fold increase in NK and NKT cells (p <
      0.009 and p < 0.02, respectively). DC were mobilized with a 11.5-fold increase in
      type 2 (p < 0.004) and a 8.5-fold increase in type 1 DC (p < 0.003). The patients
      received a mean of: 2.2 x 10(7)/kg +/- 1.4 x 10(7)/kg of NK cells, 0.95 x
      10(7)/kg +/- 0.81 x 107/kg of NKT cells, 0.43 x 107/kg +/- 0.53 x 10(7)/kg of
      type 1 DC, 0.3 v 10(7)/kg +/- 0.45 x 10(7)/kg of type 2 DC and 1.4 x 10(7)/kg +/-
      1.2 x 10(7)/kg of regulatory T cells. Using intermediate doses of G-CSF, we have
      demonstrated the mobilization of different lymphocyte subsets, in particular
      regulatory T cells and DC, which can be expanded later and used in the treatment
      of cancer and autoimmune diseases.

PMID- 15969627
TI  - Hematopoietic progenitor cell mobilization by granulocyte colony-stimulating
      factor and erythropoietin in the absence of matrix metalloproteinase-9.
AB  - The use of mobilized hematopoietic progenitor cells (HPC) has largely replaced
      the use of bone marrow HPC for autologous and allogeneic transplantation;
      however, the mechanisms of HPC mobilization remain unclear. A better
      understanding of these mechanisms, may allow the development of improved
      (potentially more rapid and/or higher yield) HPC mobilization strategies,
      especially for patients who mobilize poorly using current mobilization protocols.
      Clinically, granulocyte colony-stimulating factor (G-CSF) is widely used to
      induce HPC mobilization, and evidence suggests that metalloproteinase enzymes
      released by activated granulocytes play an important role in the G-CSF-induced
      HPC mobilization. These enzymes may act to disrupt putative cell-cell and/or cell
      extracellular matrix interactions within the hematopoietic microenvironment
      thereby releasing HPC into the blood. Matrix metalloproteinase-9 (MMP-9) appears
      to be important for G-CSF-induced mobilization. Using an MMP-9 knock-out (KO)
      mouse model, we investigated the role of MMP-9 in G-CSF and erythropoietin (EPO)
      based HPC mobilization at clinically relevant cytokine doses. There were few
      hematologic or hematopoietic differences between the wild-type and MMP-9KO mice
      during steady-state hematopoiesis. When treated subcutaneously with EPO (500 U/kg
      per day) and G-CSF (15 microg/kg per day) for 5 days and assayed on day 6,
      similarly increased extramedullary hematopoiesis and numbers of HPC in the spleen
      and blood were observed for both the wild-type and MMP-9KO mice. These data
      demonstrate that MMP-9 is not required for EPO + G-CSF mobilization and that
      alternative mobilization mechanisms must be active at clinically relevant
      cytokine concentrations.

PMID- 15969628
TI  - Human adult CD34- progenitor cells functionally express the chemokine receptors
      CCR1, CCR4, CCR7, CXCR5, and CCR10 but not CXCR4.
AB  - The homing and tissue-specific recruitment of bone marrow-derived progenitor
      cells is a major issue in stem cell research and therapy. Chemokine biology plays
      a central role in the homing and trafficking of leukocytes. Here we show
      functional expression of the chemokine receptors CCR1, CCR4, CCR7, CCR10, and
      CXCR5 on primary isolates of CD34- mesenchymal progenitor cells as well as
      immortalized mesenchymal stem cell (MSC) lines. Although mRNA expression of CXCR4
      was detected in both primary cells and immortalized clones, the receptor was not
      expressed on the cell surface. On the basis of this expression profile, the MSC
      could potentially home to secondary lymphatic organs (CCR7, CXCR5), skin (CCR4,
      CCR10), small intestine (CCR10), and salivary glands (CCR10). To study tissue
      specific homing, murine CD34- MSC lines showing concordant chemokine receptor
      expression were either transiently labeled with CMFDA, or were stably transfected
      with green fluorescent protein (GFP) expression plasmids. The MSC were then
      injected into syngeneic healthy mice, and the distribution of the cells
      determined. The injected cells efficiently homed to spleen, thymus, and lymph
      nodes. In addition, cells were found in the mucosa of the small intestine, skin,
      and salivary gland. No significant recruitment to bone marrow, liver, or kidney
      was seen. Chemokine biology may play an important role in the homeostasis and
      potentially tissue recruitment of early adult progenitor cells.

PMID- 15969629
TI  - Propagation, expansion, and multilineage differentiation of human somatic stem
      cells from dermal progenitors.
AB  - We isolated multipotential mesenchymal stem cells (MSC) from human postnatal
      dermal tissues. The isolated cells were expanded and maintained for over 100
      population doublings with retention of their chromosomal complement and potential
      for multilineage differentiation. Progeny of cell lines established from a single
      dermal MSC could be differentiated into adipogenic, osteogenic, and myogenic
      lineages, consistent with the conclusion that we established a clonal,
      multipotential, somatic MSC cell line. This study is the first to show potential
      growth of multipotential human MSC cell lines from a single cell that can be used
      for the engineering of tissues in vivo. Clonal growth of MSCs presents profound
      implications in our understanding of differentiation and development, and should
      provide a valuable resource for tissue repair.

PMID- 15969634
TI  - Invited review: Neuroprotective properties of certain beta-adrenoceptor
      antagonists used for the treatment of glaucoma.
AB  - Although it is known that ganglion cell death causes loss of vision in glaucoma,
      the pathogenesis of the disease is complex, probably involving an initial
      ischemic insult to the ganglion cell axons and glial cells with the ganglion cell
      bodies eventually being affected. It may therefore be necessary to blunt many
      stages in the pathogenesis of the disease to obtain a clinically effective
      neuroprotective strategy. In animal experiments, one cause of ganglion cell death
      in ischemia is an overactivation of glutamate receptors and a subsequent rise in
      intracellular levels of sodium and calcium ions as well as a generation of
      reactive oxygen species. In contrast, optic nerve death in ischemia is mainly
      caused by an influx of sodium and reversal of the sodium/calcium exchanger, which
      leads to a rise in intracellular calcium. Thus, a substance that reduces the
      influx of sodium will protect the ganglion cell axon, and if it also reduces
      calcium influx and/or acts as an antioxidant it will protect the ganglion cell
      body in addition. Of all antiglaucoma drugs, only beta-blockers have both calcium
      and sodium channel blocking activity, with betaxolol being the most efficacious
      of those analyzed. In addition, of the tested ophthalmic beta-blockers only
      metipranolol has powerful antioxidant properties. Moreover, laboratory studies on
      rats have shown that topically applied beta-blockers attenuate ischemic injury to
      ganglion cells by mechanisms that do not appear to involve an action on beta
      receptors. Thus, of the substances used to lower intraocular pressure in
      glaucoma, beta-blockers have unique additional characteristics that also give
      them the capacity to act as neuroprotectants.

PMID- 15969635
TI  - Tolerance to the miotic effect of sarin vapor in rats after multiple low-level
      exposures.
AB  - Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin
      (GB) results in the accumulation of acetylcholine and excessive cholinergic
      stimulation. There are few data in the literature regarding the effects of
      multiple low-level exposures to GB and other organophosphorous compounds via
      relevant routes of exposure. Therefore, the present study was undertaken, and is
      the first, to investigate the effect of low-level repeated whole-body inhalation
      exposures to GB vapor on pupil size and cholinesterase activity in the eyes and
      blood. Male Sprague-Dawley rats were exposed to 4.0 mg/m3 of GB vapor for 1 h on
      each of 3 consecutive days. Pupil size and cholinesterase activities were
      determined at various points throughout the exposure sequence. The results
      demonstrate that multiple inhalation exposures to GB vapor produce a decrease in
      the miotic potency of GB in rats. This tolerance developed at a dose of GB that
      produced no overt signs of intoxication other than miosis. AChE and
      butyrylcholinesterase activity did not increase throughout the exposure sequence,
      suggesting that the tolerance cannot be attributed to a reduced inhibitory effect
      of GB. A decrease in the amount of GB present in the eye occurred after the third
      exposure. However, this change is insufficient to explain the tolerance, as there
      was no corresponding increase in AChE activity. Thus, the mechanism mediating the
      miotic tolerance observed after multiple inhalation exposures to the nerve agent
      GB remains uncertain, although several possibilities can be excluded based on the
      results of the present study.

PMID- 15969636
TI  - Characterization of endothelin-converting enzyme activities in ARPE-19 cells, a
      human retinal pigmented epithelial cell line.
AB  - Elevated endothelin-1 (ET-1) levels are detected in patients with glaucoma. ET-1
      is produced from its precursor, Big ET-1, by endothelin-converting enzyme (ECE).
      Characterization of ET- 1 secretion and ECE activity was performed in ARPE-19
      cells, a human retinal pigmented epithelial cell-line. The ET(B) receptor but not
      the ET(A) receptor was detected by immunoblotting and cross-linking using 125I-ET
      1 at the plasma membrane (PM). Tumor necrosis factor-alpha (10 nmol/L) induced a
      700% increase in ET-1 levels and such an effect was further potentiated by BQ788,
      an ET(B) receptor antagonist, suggesting the involvement of ET(B) receptor in ET
      1 clearance. Big ET-1-converting activities were detected in both the PM and
      cytosol. Phosphoramidon, thiorphan, acidification, and phenanthroline inhibited
      PM ECE activity; the cytosolic ECE activity was not affected by phenanthroline
      but was inhibited by the others. In contrast, ECE cytosolic activities were
      activated by acidification (pH 6.4), suggesting the involvement of ECE-2 or
      cathepsin-like activity. Pepstatin, a potent inhibitor of cathepsins, and
      phosphoramidon, a potent inhibitor of ECE, inhibited the cytosolic conversion of
      Big ET-1 peptide by 46% and 35%, respectively, whereas the combination of both
      inhibited the cytosolic activity by 93%. Based on immunoblotting, ECE-1 was
      detected only at the PM, whereas ECE-2 and cathpesins B and D were detected in
      the cytosol. In summary, ET-1 production in RPE is regulated by at least two
      isoforms of ECE, (cytosolic and PM) as well as cathepsins.

PMID- 15969637
TI  - Intraocular properties of hexadecyloxypropyl-cyclic-cidofovir in Guinea pigs.
AB  - OBJECTIVE: We previously reported a long-lasting crystalline lipid pro-drug of
      cyclic cidofovir, hexadecyloxypropyl-cyclic-cidofovir (HDP-cCDV), to treat
      experimental retinitis in rabbit eyes. With HDP-cCDV there was a longer
      intraocular therapeutic effect than with cidofovir (CDV) and no toxicity with 100
      microg/eye. It has been known that CDV and related analogues lower intraocular
      pressure (IOP) after local use, and it is also accepted that the guinea pig is a
      better model to study this toxicity before human clinical trials. METHODS: HDP
      cCDV was intravitreally injected into 10 guinea pig eyes in doses of 4, 9, and 18
      microg in 20 microL/eye. An 18-microg quantity is the dose equivalent to 100
      microg/eye in the rabbit. Only one eye of each animal received drug and the
      fellow eye served as the control. After injection, the eyes were monitored with
      tonometry, ophthalmoscopy, electroretinography (ERG), and histology. RESULTS:
      Intravitreal injections of doses of 18 microg/eye or lower revealed no toxicity
      and a high therapeutic index (132,000 to 3300 times higher than the 50% effective
      concentration for human cytomegalovirus) during 10 weeks of observation. The
      crystalline drug depot was ophthalmoscopically visible in the inferior vitreous
      cavity for 5-10 weeks. There was no difference in IOP between the drug-injected
      and control eyes at any time points (P > 0.05) except for day 3 after drug
      injection (P = 0.0338). All eyes demonstrated a normal ERG waveform with no
      differences between the treated and the fellow control eyes (P = 0.85). Histology
      revealed normal morphology and structures of the retina and ciliary body in all
      eyes (with or without treatment). CONCLUSION: Crystalline HDP-cCDV may be a long
      lasting and safer alternative to cidofovir to treat CMV retinitis without the
      retinal or ciliary body toxicity observed with CDV.

PMID- 15969638
TI  - Tissue distribution of moxaverine-hydrochloride in the rabbit eye and plasma.
AB  - OBJECTIVE: The aim of this study was to determine the tissue distribution and
      epithelial penetration of moxaverine-hydrochloride (MOX) in the rabbit eye.
      METHODS: For systemic application, a radioactively labeled MOX solution was
      injected into the ear vein of Dutch-belted pigmented male rabbits. For topical
      dosing, an identical solution was administered. At predetermined time points,
      rabbits were sacrificed, the eyes dissected, and the amount of MOX in the ocular
      tissues measured. To examine the MOX permeability across the corneal epithelium,
      transport studies using rabbit corneal epithelial cell culture were conducted and
      the respective apparent permeability coefficient in absorptive (a to b) or
      secretive (b to a) direction was calculated. RESULTS: Topical delivery resulted
      in high concentrations of MOX in the cornea and conjunctiva, although other
      tissues of the anterior part yielded lower MOX concentrations. In the tissues of
      the posterior part, high amounts were detected in the retina. Plasma levels were
      low. The apparent permeability coefficient across corneal epithelial cell layers
      was in the range of 10(5) cm/s, exhibiting no apparent directionality.
      CONCLUSION: A topical dosing of MOX to posterior regions of the eye seems
      feasible. MOX levels in the posterior part of the eye were remarkably high,
      without causing stringent plasma levels. The high apparent permeability
      coefficient of MOX across the corneal epithelial cell layers might be caused by
      the lipophilic nature of the drug and was in the range of other compounds with
      comparable physicochemical properties.

PMID- 15969639
TI  - Evaluation of the stability of extemporaneously prepared ophthalmic formulation
      of mitomycin C.
AB  - Mitomycin C (MMC) is a cytostatic agent topically used in conjunctival neoplasms,
      secondary to glaucoma filtering, pterygium, and strabismus surgery to increase
      the success rate. The topical formulation of MMC for ocular use is always
      extemporaneously prepared. Our study evaluated the stability of extemporaneously
      prepared formulations of MMC at different concentrations (150, 300, & 600
      microg/mL) kept at different temperatures (25 degrees , 4 degrees , and -70
      degrees C) and at different pH range (6, 7, and 8). Aliquots from the above
      formulations were subjected for quantification of MMC on days 0, 7, 14, 21, and
      28 using high-performance liquid chromatography. MMC stored at 25 degrees C for 6
      months was also subjected to flow cytometry and compared to freshly prepared MMC.
      The results indicated that the degradation of MMC is very high in acidic pH at
      room temperature. Increasing the pH to 7 or 8 and keeping MMC at low temperatures
      significantly decreased the degradation of MMC. Interestingly, the flow cytometry
      data revealed that the 6-month-old MMC showed an antiproliferative effect
      compared to that of freshly prepared MMC. To conclude, the extemporaneously
      prepared MMC at pH between 7 and 8 and stored in the refrigerator can increase
      the duration of its stability. However, the antiproliferative study using flow
      cytometry revealed that degraded MMC retained its activity even after
      degradation.

PMID- 15969640
TI  - Do injections of 5-fluorouracil after trabeculectomy have toxic effects on the
      anterior segment?
AB  - OBJECTIVE: To discourage fibrosis of the filtering bleb, 5 fluorouracil (5-FU)
      may be injected after trabeculectomy. 5-FU is an antimetabolite that also can
      damage extraocular tissues at concentrations as low as 0.5%. This study
      ascertained whether repeated injection of 5-FU has toxic effects on intraocular
      structures. METHODS: After unilateral trabeculectomy in anesthetized New Zealand
      rabbits, 5-FU (5.0 mg/0.1 mL) was injected at the trabeculectomy site every 5
      days for 15 days. Evaluation included slit-lamp examination, confocal microscopy,
      and intraocular pressure (IOP). After sacrifice, aqueous humor (AH) was drawn and
      eyes excised for scanning electron microscopy (SEM) and light microscopy.
      RESULTS: The 5-FU injection not decrease IOP beyond trabeculectomy alone. Bleb
      height remained constant, thickness increased, and vascularity decreased. No
      changes in cornea or anterior segment were observed. No inflammation was observed
      in the bleb or surrounding tissues by slit-lamp or histologic examination.
      Protein in AH increased from 0.6 +/- 0.5 microg/mL at baseline to 19.8 +/- 4.4
      microg/mL after trabeculectomy but only to 0.9 +/- 0.6 microg/mL after
      trabeculectomy plus 5-FU. Both in vivo confocal microscopy and SEM revealed
      deleterious effects on corneal epithelial and endothelial cells with a minor
      shift toward smaller cells. CONCLUSIONS: In this study 5-FU did not provoke an
      intraocular inflammatory response and had minimal effect on extraocular
      structures. Changes in corneal epithelium and endothelium detectable by confocal
      microscopy suggest a small toxic effect. These in vivo measurements by confocal
      microscopy were confirmed by SEM. Repeated administration did not cause
      additional cumulative toxic effects in the anterior segment. Therefore, multiple
      injections of 5- FU into the filtering bleb pose minimal risk to intraocular
      structures.

PMID- 15969641
TI  - A comparison of therapeutic regimens containing moxifloxacin 0.5% ophthalmic
      solution and gatifloxacin 0.3% ophthalmic solution for surgical prophylaxis in
      patients undergoing LASIK or LASEK.
AB  - The purpose of these two studies was to compare the safety and tolerability of
      moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% ophthalmic solution
      for use with laser-assisted in situ keratomileusis (LASIK) and laser-assisted
      subepithelial keratomileusis (LASEK) patients. Treatment with the two antibiotic
      regimens was randomly assigned to fellow eyes of each patient. The LASIK study
      showed no difference between the two therapies in terms of visual acuity, pupil
      size, SPK, edema, haze, day- and nighttime glare, halos, clarity of day or night
      vision, and dry eye symptoms up to 1 week after surgery. Patients reported no
      preference between the two antibiotics on the basis of ease of use, irritation,
      redness, itching, gritty, sandy or scratchy feeling, speed of recovery, overall
      vision, or overall comfort up to 7 days after LASIK surgery. Corneal healing
      after LASEK surgery was equivalent for the antibiotic regimens containing
      moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% ophthalmic solution.
      When comparing safety and tolerability, these findings suggest an equivalent role
      for these fluoroquinolone antibiotics in surgical prophylaxis.

PMID- 15969642
TI  - Efficacy of the dorzolamide/timolol fixed combination versus latanoprost in the
      treatment of ocular hypertension or glaucoma: combined analysis of pooled data
      from two large randomized observer and patient-masked studies.
AB  - In previous analyses of primary efficacy data from two randomized clinical
      trials, standard dosing regimens of the dorzolamide/timolol fixed combination
      (COSOPT) and latanoprost (XALATAN) were shown to have equivalent efficacy with
      regard to reduction in mean daytime diurnal intraocular pressure (IOP). We
      performed additional post hoc analyses of pooled data from these studies to
      compare further the efficacy of the two treatments. The studies used identical 3
      month, parallel group, randomized, observer-masked and patient-masked,
      multicenter designs. Patients with a baseline IOP > or = 24 mm Hg were randomized
      to either the 2% dorzolamide/0.5% timolol combination eye drops twice daily (n =
      273) or 0.005% latanoprost eye drops once daily (n = 271). The IOP measurements
      were made at 8 AM, 10 AM, 2 PM, and 4 PM at the baseline visit and then on each
      of the 3 monthly assessment days. The following measures were analyzed on a post
      hoc basis: 1) percentages of patients meeting target levels of IOP reduction; 2)
      mean IOP reduction in those patients with high IOP (> or =30 mmHg) at baseline;
      3) mean IOP at each of the assessment time points during a day. A total of 259
      patients in the dorzolamide/timolol group and 268 patients in the latanoprost
      group were included in the efficacy analysis. At 3 months, both treatments showed
      similar efficacy with regard to the percentages of patients who achieved target
      levels of IOP reduction (e.g., 40% IOP reduction in 15% of dorzolamide/timolol
      combination patients and 13% of latanoprost patients), mean IOP reduction in
      those patients with high IOP at baseline (dorzolamide/ timolol combination, 12.5
      mmHg, latanoprost, 12.6 mmHg), and mean IOP at each time point during the day. By
      the measures used in this analysis, the dorzolamide/timolol combination and
      latanoprost were equally effective at lowering IOP in patients with ocular
      hypertension or glaucoma.

PMID- 15969643
TI  - Water-drinking test in patients with primary open-angle glaucoma while treated
      with different topical medications.
AB  - OBJECTIVE: Reduction and diurnal stabilization of the intra-ocular pressure (IOP)
      is the mainstay of treatment for glaucoma. Fluctuations of IOP in glaucomatous
      patients can also be induced by the osmotic variations caused by water ingestion.
      Such influence can be studied by means of the water-drinking test (WDT). The aim
      of this study was to perform the WDT in patients with primary open-angle glaucoma
      (POAG) while they were being treated with different IOP-lowering medications, to
      test the effect of drugs with different mechanisms of action on the ability to
      maintain a stable IOP. METHODS: A total of 280 POAG patients were enrolled, 40
      patients per group for each of the tested medications (timolol, dorzolamide,
      brinzolamide, travoprost,latanoprost, bimatoprost, and brimonidine). After
      baseline IOP measurement, all patients underwent WDT (1000 mL of water in 10
      min). The IOP was measured at 15-min intervals until the return of IOP to
      baseline values. The main outcomes measured were mean IOP peak, mean IOP
      percentage increase, and mean time for returning to baseline IOP value. RESULTS:
      The highest mean IOP peak was found with timolol, whereas no difference was found
      among the other drugs. The highest mean IOP percentage increase was found with
      timolol, whereas bimatoprost showed an IOP percentage increase significantly
      lower than latanoprost, dorzolamide, and brinzolamide. The duration of IOP
      increase was shortest for bimatoprost and longest for timolol. CONCLUSION: This
      study suggests that topical medications that enhance outflow (e.g., bimatoprost,
      latanoprost, travoprost, and brimonidine) may provide, under stressful conditions
      such as the WDT, better IOP stabilization than medications that decrease aqueous
      humor inflow, such as timolol and topical carbonic anhydrase inhibitors.

PMID- 15969645
TI  - The Tropical Biominer Project: mining old sources for new drugs.
AB  - The Tropical Biominer Project is a recent initiative from the Federal University
      of Minas Gerais (UFMG) and the Oswaldo Cruz foundation, with the participation of
      the Biominas Foundation (Belo Horizonte, Minas Gerais, Brazil) and the start-up
      Homologix. The main objective of the project is to build a new resource for the
      chemogenomics research, on chemical compounds, with a strong emphasis on natural
      molecules. Adopted technologies include the search of information from
      structured, semi-structured, and non-structured documents (the last two from the
      web) and datamining tools in order to gather information from different sources.
      The database is the support for developing applications to find new potential
      treatments for parasitic infections by using virtual screening tools. We present
      here the midpoint of the project: the conception and implementation of the
      Tropical Biominer Database. This is a Federated Database designed to store data
      from different resources. Connected to the database, a web crawler is able to
      gather information from distinct, patented web sites and store them after
      automatic classification using datamining tools. Finally, we demonstrate the
      interest of the approach, by formulating new hypotheses on specific targets of a
      natural compound, violacein, using inferences from a Virtual Screening procedure.

PMID- 15969646
TI  - The network of transcriptional interactions imposes linear constrains in the
      genome.
AB  - Two prokaryotic organisms for which transcriptional regulatory interactions have
      been well elucidated by experimental means are Escherichia coli and Bacillus
      subtilis. Here we show, with the help of simulations and from known data, the
      importance of proximity of the transcription factor gene and the respective
      regulated gene in regulatory networks. We discuss the importance of the location
      of external sensing machinery close to the genes for transcription factors that
      regulate them in light of our finding.

PMID- 15969647
TI  - Xylella and Xanthomonas Mobil'omics.
AB  - The gamma-proteobacterium Xanthomonadales groups two closely related genera of
      plant pathogens, Xanthomonas and Xylella. Whole genome sequencing and comparative
      analyses disclosed a high degree of identity and co-linearity of the chromosome
      backbone between species and strains. Differences observed are usually clustered
      into genomic islands, most of which are delimited by genetic mobile elements.
      Focus is given in this paper to describe which groups of mobile elements are
      found and what is the relative contribution of these elements to Xanthomonas and
      Xylella genomes. Insertion sequence (IS) elements have invaded the Xanthomonas
      genome several times, whereas Xylella is rich in phage-related regions. Also,
      different plasmids are found inhabiting the bacterial cells studied here.
      Altogether, these results suggest that the integrative elements such as phages
      and transposable elements as well as the episomal plasmids are important drivers
      of the genome evolution of this important group of plant pathogens.

PMID- 15969648
TI  - Non-gamma-proteobacteria gene islands contribute to the Xanthomonas genome.
AB  - Horizontal gene transfer, a process through which genomes acquire sequences from
      distantly related organisms, is believed to be a major source of genetic
      diversity in bacteria. A central question concerning the impact of gene transfer
      on bacterial genome evolution is the proportion of horizontally transferred
      sequences within genomes. Through BLAST search, we found that the genomes of two
      phytopathogens, Xanthomonas campestris pv. campestris and Xanthomonas axonopodis
      pv. citri, have close to 40% of the genes with the highest similarity to genes
      from phylogenetically distant organisms (non-gamma-proteobacteria). Most of these
      genes are found to be contiguous in the genome, forming genome islands, which may
      have been transferred from other organisms. Overall, the total number of genes
      within genome islands corresponds to almost one quarter of the entire xanthomonad
      genomes. Interestingly, many of the genes in these islands are functionally
      related to plant pathogenesis and virulence. Thus, these results suggest that
      horizontally transferred genes are clustered in the genome, and may facilitate
      fitness in new environments, as in the case of plant-bacteria interaction.

PMID- 15969649
TI  - Pathogenomics analysis of Leishmania spp.: flagellar gene families of putative
      virulence factors.
AB  - The trypanosomatid flagellar apparatus contains conventional and unique features,
      whose roles in infectivity are still enigmatic. Although the flagellum and the
      flagellar pocket are critical organelles responsible for all vesicular
      trafficking between the cytoplasm and cell surface, still very little is known
      about their roles in pathogenesis and how molecules get to and from the flagellar
      pocket. The ongoing analysis of the genome sequences and proteome profiles of
      Leishmania major and L infantum, Trypanosoma cruzi, T. brucei, and T. gambiensi (
      www.genedb.org ), coupled with our own work on L. chagasi (as part of the
      Brazilian Northeast Genome Program- www.progene.ufpe.br ), prompted us to
      scrutinize flagellar genes and proteins of Leishmania spp. promastigotes that
      could be virulence factors in leishmaniasis. We have identified some overlooked
      parasite factors such as the MNUDC-1 (a protein involved in nuclear development
      and genomic fusion) and SQS (an enzyme of sterol biosynthesis), among the
      described flagellar gene families. A database concerning the results of this
      work, as well as of other studies of Leishmania and its organelles, is available
      at http://nugen.lcc.uece.br/LPGate . It will serve as a convenient bioinformatics
      resource on genomics and pathology of the etiological agents of leishmaniasis.

PMID- 15969650
TI  - Protein mapping of the salivary complex from a hematophagous leech.
AB  - The salivary complex of leeches contains many components able to modulate
      physiological mechanisms, such as coagulation and fibrinolysis, and it is
      composed by the salivary glands and proboscis, encompassing two different
      proteomes. The bidimensional electrophoretic pattern of the salivary complex from
      the Haementeria depressa leech revealed a total of 352 spots, 103 in common with
      the muscular tissue and 249 exclusive from the salivary complex as detected by
      silver staining; these spots showed isoelectric points from 3.5 to 9.5 and
      covered an apparent molecular weight range from 10 to 105 kDa. The following
      isoforms of proteins were identified by mass spectrometry analysis: antiplatelet
      protein, myohemerythrin and carbonic anhydrase. Since the leeches were not fed
      for about 2-3 months to stimulate the secretion of proteins that facilitates the
      blood metabolism, these most abundant proteins in the salivary complex excised
      from leeches, are expected to play a role during feeding and might have some anti
      hemostatic properties. Furthermore, by zymography, a gelatinolytic and a
      fibrinolytic protein were identified.

PMID- 15969651
TI  - An evolving neural network for the interpretation of gene expression patterns.
AB  - It is of central interest in biology to understand how gene activity networks are
      coordinated and integrated in the cell. Within the field of genomics, microarray
      technologies have become a powerful technique for monitoring simultaneously the
      expression patterns of thousands of genes under different sets of conditions. A
      main task now is to propose analytical methods that can suggest which groups of
      genes are activated by similar conditions. We review several techniques based on
      self-organizing map and clustering algorithms but implemented through a network
      of units controlled by biologically inspired functions (see Table 1). The
      computer tool, named NBIA, permits a categorization that generates a set of gene
      groups with coordinated expression patterns.

PMID- 15969652
TI  - UDP-glucose dehydrogenases of maize: a role in cell wall pentose biosynthesis.
AB  - UDPGDH (UDP-D-glucose dehydrogenase) oxidizes UDP-Glc (UDP-D-glucose) to UDP-GlcA
      (UDP-D-glucuronate), the precursor of UDP-D-xylose and UDP-L-arabinose, major
      cell wall polysaccharide precursors. Maize (Zea mays L.) has at least two
      putative UDPGDH genes (A and B), according to sequence similarity to a soya bean
      UDPGDH gene. The predicted maize amino acid sequences have 95% similarity to that
      of soya bean. Maize mutants with a Mu-element insertion in UDPGDH-A or UDPGDH-B
      were isolated (udpgdh-A1 and udpgdh-B1 respectively) and studied for changes in
      wall polysaccharide biosynthesis. The udpgdh-A1 and udpgdh-B1 homozygotes showed
      no visible phenotype but exhibited 90 and 60-70% less UDPGDH activity
      respectively than wild-types in a radiochemical assay with 30 microM UDP-glucose.
      Ethanol dehydrogenase (ADH) activity varied independently of UDPGDH activity,
      supporting the hypothesis that ADH and UDPGDH activities are due to different
      enzymes in maize. When extracts from wild-types and udpgdh-A1 homozygotes were
      assayed with increasing concentrations of UDP-Glc, at least two isoforms of
      UDPGDH were detected, having K(m) values of approx. 380 and 950 microM for UDP
      Glc. Leaf and stem non-cellulosic polysaccharides had lower Ara/Gal and Xyl/Gal
      ratios in udpgdh-A1 homozygotes than in wild-types, whereas udpgdh-B1 homozygotes
      exhibited more variability among individual plants, suggesting that UDPGDH-A
      activity has a more important role than UDPGDH-B in UDP-GlcA synthesis. The fact
      that mutation of a UDPGDH gene interferes with polysaccharide synthesis suggests
      a greater importance for the sugar nucleotide oxidation pathway than for the myo
      inositol pathway in UDP-GlcA biosynthesis during post-germinative growth of
      maize.

PMID- 15969654
TI  - Human mast cell chemokines receptors: implications for mast cell tissue
      localization in asthma.

PMID- 15969653
TI  - Effects of nitric oxide donors on cybrids harbouring the mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes (MELAS) A3243G
      mitochondrial DNA mutation.
AB  - Reactive nitrogen and oxygen species (O2*-, H2O2, NO* and ONOO-) have been
      strongly implicated in the pathophysiology of neurodegenerative and mitochondrial
      diseases. In the present study, we examined the effects of nitrosative and/or
      nitrative stress generated by DETA-NO {(Z)-1-[2-aminoethyl-N-(2
      ammonioethyl)amino]diazen-1-ium-1,2-diolate}, SIN-1 (3-morpholinosydnonimine
      hydrochloride) and SNP (sodium nitroprusside) on U87MG glioblastoma cybrids
      carrying wt (wild-type) and mutant [A3243G (Ala3243-->Gly)] mtDNA (mitochondrial
      genome) from a patient suffering from MELAS (mitochondrial myopathy,
      encephalopathy, lactic acidosis and stroke-like episodes). The mutant cybrids had
      reduced activity of cytochrome c oxidase, significantly lower ATP level and
      decreased mitochondrial membrane potential. However, endogenous levels of
      reactive oxygen species were very similar in all cybrids regardless of whether
      they carried the mtDNA defects or not. Furthermore, the cybrids were insensitive
      to the nitrosative and/or nitrative stress produced by either DETA-NO or SIN-1
      alone. Cytotoxicity, however, was observed in response to SNP treatment and a
      combination of SIN-1 and glucose-deprivation. The mutant cybrids were
      significantly more sensitive to these insults compared with the wt controls.
      Ultrastructural examination of dying cells revealed several characteristic
      features of autophagic cell death. We concluded that nitrosative and/or nitrative
      stress alone were insufficient to trigger cytotoxicity in these cells, but cell
      death was observed with a combination of metabolic and nitrative stress. The
      vulnerability of the cybrids to these types of injury correlated with the
      cellular energy status, which were compromised by the MELAS mutation.

PMID- 15969655
TI  - Non-steroidal anti-inflammatory drugs-induced urticaria and angioedema: more
      research on mechanisms needed.

PMID- 15969656
TI  - Paracetamol, antioxidants and asthma.

PMID- 15969657
TI  - Remodelling of airway smooth muscle in asthma: what sort do you have?
AB  - BACKGROUND: Shortening of smooth muscle around airways is the basis of symptoms
      and abnormal lung function in asthma. The airway wall is increased in thickness
      in small and large airways asthma, in relation to the clinical severity of asthma
      and the airway smooth muscle layer is the main contributor to this thickening.
      The relative contributions of more airway smooth muscle cells, bigger cells or
      more extracellular matrix to the increased thickness of the smooth muscle layer
      in asthma is not clear and has been examined in only a small number of cases,
      Studies of the natural history of asthma suggest that the clinical severity of
      asthma is relatively constant over time, deficits in lung function compared with
      nonasthmatic subjects occur early in the course of the disease and the decline in
      lung function with age is increased in asthma. HYPOTHESIS: The observations from
      studies of the quantitative pathology and the natural history of asthma might be
      combined in the hypothesis that the severity of asthma is determined early (in
      its natural history) and is related mainly to increased volume density of airways
      smooth muscle cells (hyperplasia) and that later deposition of extracellular
      matrix from larger, hypertrophic smooth muscle cells results in fixed and
      increasing deficits in lung function. SPECULATION: The relative contribution of
      more smooth muscle cells, bigger cells and extracellular matrix will be
      determined by unbiased stereological measurements in many cases of asthma of
      varying severity. The outcomes of such studies will be methods of monitoring and
      of treatment that will be tailored to the sort of smooth muscle modelling that is
      present in individual cases.

PMID- 15969658
TI  - CCL17 and CCL22 attenuate CCL5-induced mast cell migration.
AB  - BACKGROUND: Mast cells (MCs) accumulate at sites of allergic mucosal inflammation
      where they act as central effectors and regulatory cells. Chemokines are believed
      to be crucial for the recruitment of MCs to sites of inflammation. We recently
      reported that human umbilical cord blood MCs (CBMCs) expresses the CC chemokine
      receptors, CCR1 and CCR4. We found a unique response profile to ligands of the
      respective receptors in which, of all tested ligands, only CCL5/RANTES-induced
      migration. OBJECTIVE: To further investigate the function of CCR4 in MCs.
      METHODS: CBMCs were used for competition binding experiments, migration, and
      intracellular calcium mobilization and release response studies. RESULTS: The
      natural ligands for CCR4, CCL17/TARC and CCL22/MDC could both compete for binding
      with radiolabelled CCL5. Further, both CCL17 and CCL22 act as CCR4 antagonists by
      inhibiting CCL5-induced migration. Although both CCL17 and CCL22 caused
      mobilization of intracellular calcium, none of them induced migration or
      histamine release. CONCLUSIONS: These results suggest that CCL5-induced migration
      of MCs via CCR4 can be regulated by the natural agonists CCL17 and CCL22, which
      are up-regulated at sites of allergic inflammation.

PMID- 15969659
TI  - Oral aspirin challenges in patients with a history of intolerance to single non
      steroidal anti-inflammatory drugs.
AB  - Summary Background In the clinical practice patients with a history of acute
      urticaria induced by a single non-steroidal anti-inflammatory drug (NSAID) and
      seeking for safe alternative drugs generally undergo tolerance tests with
      alternative NSAIDs that have little or no cyclooxygenase-1 (COX-1) enzyme
      inhibitory activity. This practice does not allow for the detection of single
      NSAID reactors and may lead to unnecessary avoidance of many potentially useful
      NSAIDs. OBJECTIVE: Evaluate aspirin challenge as a means to distinguish single
      from multiple NSAID intolerance in patients with a clinical history of acute
      urticaria induced by a single NSAID. Methods One hundred and seventeen otherwise
      normal subjects with a history of acute urticaria following the ingestion of a
      single NSAID (pyrazolones (n=58), nimesulide (n=17), propionic acid derivatives
      (n=13), aryl acetic acid derivatives (n=14), acetaminophen (n=9), piroxicam
      (n=5), and indometacin (n=1)) underwent single-blind placebo-controlled oral
      challenges with aspirin. Aspirin-intolerant subjects underwent further tolerance
      tests drugs exerting little or no inhibitory activity on COX-1 enzyme (including
      paracetamol, nimesulide, rofecoxib, tramadol, and floctafenine). Results Aspirin
      induced urticaria in 28/117 (24%) patients. Five out of 28 (18%) aspirin reactors
      did not tolerate alternative NSAID on subsequent oral challenges. Conclusion In
      subjects with a history of urticaria induced by a single NSAID (other than
      aspirin) the diagnostic workup should start with an aspirin challenge in order to
      detect single/multiple NSAID reactors.

PMID- 15969660
TI  - Improvements in an oral aspirin challenge protocol for the diagnosis of aspirin
      hypersensitivity.
AB  - Oral aspirin challenge (OAC) is used to confirm aspirin hypersensitivity (AHs)
      but there is no consensus on a standardized protocol. As a prior clinical history
      of adverse reactions to aspirin is poorly predictive of a positive result from
      formal aspirin challenge, many patients have an OAC performed. We retrospectively
      identified and prospectively validated how a 1-day OAC protocol could be
      modified, and patient selection improved, to deliver a safe and more efficient
      service. In a retrospective audit of 45 OACs using a 2 h dose interval, all
      reactions occurred within 90 min of the threshold dose. Forty OACs were then
      performed using a 90-min dose interval. This reduced the mean duration of a
      positive and negative OAC from 6 to 5 h and from 8 to 6 h, respectively.
      Histories of multiple manifestations of AHs were found in 91.6% (11) of those
      with asthma, 87.5% (7) with angiooedema, 70.6% (12) with rhinosinusitis, 63.6%
      (7) with chronic non-vasculitic urticaria and all with anaphylaxis, who developed
      a positive OAC. None of those with anaphylaxis, 8.3% (1) with asthma and 12.5%
      (1) with angiooedema, with a positive OAC, had a history of a single
      manifestation of AHs. The efficiency of an OAC service can safely be improved by
      reduction of the dose interval from 2 to 1 (1/2) h, and more targeted patient
      selection, as the likelihood of a positive OAC increases among patients with a
      history of asthma, angiooedoema or anaphylaxis with multiple manifestations of
      AHs.

PMID- 15969661
TI  - Increased risk of asthma attacks and emergency visits among asthma patients with
      allergic rhinitis: a subgroup analysis of the investigation of montelukast as a
      partner agent for complementary therapy [corrected].
AB  - BACKGROUND: Inadequately controlled allergic rhinitis (AR) in asthmatic patients
      can contribute towards increased asthma exacerbations and poorer symptom control,
      which may increase medical resource use. We assessed asthma-related medical
      resource use and attacks in asthmatic patients who did and did not have
      concomitant AR and were adding montelukast or salmeterol to baseline treatment
      with inhaled fluticasone. METHODS: A post hoc resource use analysis of a 52-week,
      double-blind multicentre clinical trial (Investigation of Montelukast as a
      Partner Agent for Complementary Therapy) [corrected] including 1490 adults with
      chronic asthma, aged 15-72 years, with FEV(1) 50-90% of predicted and > or =12%
      increase in FEV(1) after salbutamol administration, treated with either
      montelukast 10 mg daily or salmeterol 50 microg twice daily in addition to
      fluticasone 200 microg, was undertaken. Asthma-related medical resource use
      included medical visits (defined as either an unscheduled visit [to a general
      practitioner, a specialist or a non-medical provider] or a specialist visit),
      emergency room visits and hospitalizations during follow-up. Asthma attacks were
      defined as the worsening of asthma requiring unscheduled visit, emergency visit,
      hospitalization or oral/intravenous/intramuscular corticosteroids. RESULTS: A
      self-reported history of concomitant AR was identified in 60% of the patients
      (n=893). Univariate analysis suggests that significantly more patients with
      concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and
      asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for
      treatment group, age and baseline asthma severity confirmed these results since
      the presence of concomitant AR in patients with asthma increases the likelihood
      of emergency room visit (odds ratio (OR)=2.35, 95% confidence interval (CI)=1.12
      4.80) and asthma attack (OR=1.35, 95% CI=1.03-1.77). Patients with asthma alone
      compared with patients with both conditions did not differ in terms of
      unscheduled or specialist visits and hospitalizations. CONCLUSIONS: Presence of
      self-reported concomitant AR in patients with asthma resulted in a higher rate of
      asthma attacks and more emergency room visits compared with asthma patients
      without concomitant AR.

PMID- 15969662
TI  - Characteristics of intermittent and persistent allergic rhinitis: DREAMS study
      group.
AB  - BACKGROUND: In the Allergic Rhinitis and its Impact on Asthma (ARIA)
      classification, intermittent and persistent rhinitis were proposed to replace
      seasonal and perennial allergic rhinitis (AR). AIM: To better understand the ARIA
      classification of rhinitis. METHODS: A cross-sectional study was carried out in
      591 patients consulting ENT or allergy specialists for AR and 502 control
      subjects. The diagnosis of AR was based on a score for allergic rhinitis (SFAR) >
      or =7. Patients were classified according to the four ARIA classes (mild
      intermittent, mild persistent, moderate/severe intermittent and moderate/severe
      persistent). Allergen sensitization (skin prick tests (SPTs) or specific IgE) and
      co-morbidities were examined according to the ARIA classes. RESULTS: Ten percent
      of patients had mild intermittent rhinitis, 14% mild persistent rhinitis, 17%
      moderate/severe intermittent rhinitis and 59% moderate/severe persistent
      rhinitis. Most patients with intermittent rhinitis had a pollen sensitivity, but
      5% had a single house dust mite (HDM) sensitization. Over 50% of patients with
      persistent rhinitis were allergic to pollens or HDM. Asthma was present in 24% of
      rhinitis patients and in only 2% of the control population (P<0.0001). Patients
      with moderate/severe persistent rhinitis had the highest asthma prevalence (33%).
      DISCUSSION: Intermittent and persistent rhinitis are not synonymous of seasonal
      and perennial rhinitis. Most patients consulting specialists have severe
      rhinitis. Asthma prevalence increases with duration and severity of rhinitis
      supporting the ARIA major recommendation that patients with persistent rhinitis
      should be evaluated for asthma.

PMID- 15969663
TI  - Perinatal risk factors for sensitization, atopic dermatitis and wheezing during
      the first year of life (PIPO study).
AB  - OBJECTIVE: To evaluate the influence of perinatal environmental factors on early
      sensitization, atopic dermatitis and wheezing during the first year. METHODS:
      Information on pregnancy-related factors, parental atopic history, environmental
      factors and the clinical course of the infant until age one was gathered by
      questionnaires, as part of a prospective birth cohort study (Prospective study on
      the Influence of Perinatal factors on the Occurrence of asthma and allergies
      [PIPO-study]). Quantification of total and specific IgE was performed in 810
      children and their parents. RESULTS: Early sensitization was found in 107/810
      (13%) of the infants. Multiple regression analysis showed that specific IgE in
      fathers was a risk factor for early sensitization in their daughters (adjusted
      odds ratios (OR(adj)) 2.21 (95% confidence interval (CI) 1.10-4.49); P=0.03),
      whereas in boys, day care attendance was shown to be protective for early
      sensitization (OR(adj) 0.38 (95% CI 0.20-0.71); P=0.001). Atopic dermatitis
      occurred in 195/792 infants (25%). Specific IgE in the mother (OR(adj) 1.52 (95%
      CI 1.06-2.19); P=0.02) and in the infant (OR(adj) 4.20 (95% CI 2.63-6.68);
      P<0.001) were both risk factors for the occurence of atopic dermatitis, whereas
      postnatal exposure to cats was negatively associated with atopic dermatitis
      (OR(adj) 0.68 (0.47-0.97); P=0.03). Postnatal exposure to cigarette smoke
      (OR(adj) 3.31 (95% CI 1.79-6.09); P<0.001) and day care attendance (OR(adj) 1.96
      (95% CI 1.18-3.23); P=0.009) were significantly associated with early wheezing,
      which occurred in 25% (197/795) of the infants. CONCLUSION: The effect of
      paternal sensitization and day care attendance on sensitization is gender
      dependent. Maternal sensitization predisposes for atopic dermatitis, whereas
      postnatal exposure to cats had a protective effect.

PMID- 15969664
TI  - Fecal microbiota in sensitized wheezy and non-sensitized non-wheezy children: a
      nested case-control study.
AB  - BACKGROUND: It has been suggested that intestinal microbiota of allergic and non
      allergic children differs in composition, and that microbiota-immune system
      interactions may predispose children to develop sensitization. Previous studies
      have examined fecal microbiota of allergic children with atopic dermatitis, but
      little is known about that of atopic wheezy children. OBJECTIVE: To investigate
      the composition of the fecal microbiota of young sensitized wheezy and non
      sensitized non-wheezy children, using molecular methods. METHODS: Within the
      context of a prospective birth cohort, we carried out a nested case-control study
      of sensitized wheezy children (cases) and non-sensitized non-wheezy controls.
      Cases and controls were matched for age, sex, parental atopy, allergen exposure,
      and pet ownership. We evaluated the composition of fecal microbiota by nucleic
      acid-based methods (PCR combined with denaturing gradient gel electrophoresis and
      quantification of bifidobacteria by fluorescent in situ hybridization). RESULTS:
      Thirty-three case-control pairs (mean age 4.4 years) provided stool samples.
      Comparison of total bacterial community profiles showed that each child had a
      unique fecal microbiota (mean Dice's similarity coefficient 22%, range 3.3
      60.8%). There was no difference between the groups in prevalence of Lactic Acid
      bacteria (12/33 vs. 11/33, P=0.8) or bifidobacteria (30/33 vs. 31/33, P=1.00,
      cases vs. controls). The bifidobacterial species detected were similar in both
      groups. The percentage of bifidobacteria in total fecal microflora was no
      different between cases (median 1.7%, range 0-20.8%) and controls (1.9%, 0-18.2%,
      P=0.7). However, cases with eczema had significantly fewer bifidobacteria (median
      1.6%, range 0-4.8%) than their controls (4.0%, 1.9-18.2%, P=0.05). CONCLUSION: We
      found no differences in fecal microbiota composition between sensitized wheezy
      and non-sensitized, non-wheezy children aged 3-5 years using nucleic acid-based
      methods. Differences appear to be isolated to those allergic children with
      eczema.

PMID- 15969665
TI  - Allergic reactions in the community: a questionnaire survey of members of the
      anaphylaxis campaign.
AB  - BACKGROUND: Allergic reactions to food are well recognized in both children and
      adults, but because of their relative infrequency their typical features may not
      be readily recognized by patients and their medical care givers who are not
      allergists. OBJECTIVE: We sought to investigate the circumstances and clinical
      characteristics of food allergies in adults and children in the community.
      METHODS: Self-completed questionnaire responses over a 6-month period from 109
      members of the Anaphylaxis Campaign, the major British patient resource group for
      people who have suffered severe allergic reactions. RESULTS: One hundred and nine
      respondents reported 126 reactions during the study period. Seventy-five were
      children (under 16 years, median age 6 years at the time of reaction).
      Predictably more boys than girls were reported to have had reactions but more
      women reported reactions than men (P<0.05). Although the groups were equally
      aware of their food allergies the children had undergone diagnostic tests more
      often (P<0.001). Foods were implicated in 112 (89%) of reports. Restaurants were
      implicated less often (14%) than in other series, probably reflecting British
      eating habits. Children with asthma reported more severe reactions than those
      without asthma (P=0.008), although frequency or severity of recent asthma
      symptoms was not associated with severity of allergic reaction reported. When
      available, self-injectable adrenaline was used in 35% of severe reactions and 13%
      of non-severe reactions (P=0.01). A quarter of adults who received one dose of
      adrenaline also received a second dose. CONCLUSION: The allergens implicated in
      this report reflect previous data from similar patient groups in North America.
      Asthmatic children suffer more severe reactions than non-asthmatic children. It
      appears that British adults need better access to expert care of their allergies.
      Even when it is prescribed and available self-injectable adrenaline appears under
      used in severe reactions. The incidence of severe but non-fatal allergic
      reactions in the UK may have been underestimated in the past.

PMID- 15969666
TI  - Efficacy of a management plan based on severity assessment in longitudinal and
      case-controlled studies of 747 children with nut allergy: proposal for good
      practice.
AB  - BACKGROUND: There are few data on the long-term management of children with
      peanut/nut allergy. Advice is variable and often inadequate; further reactions
      are common. There is no consensus on the criteria for prescription of rescue
      medication, particularly adrenaline. METHOD: A longitudinal prospective and case
      control study in a tertiary allergy clinic. Patients/parents/school staff of 747
      children with confirmed peanut or tree nut allergy received detailed verbal and
      written advice on nut avoidance, training in recognition and (self-) treatment of
      reactions and a written treatment plan. The severity of nut allergy was graded
      (mild-severe) and emergency medication was allocated according to our criteria:
      all received oral antihistamines, injected adrenaline (EpiPen) was given to those
      with reactions with airway narrowing, milder reactions to low-dose exposure or
      concomitant asthma. At annual follow-up over 25 906 patient-months (median: 39
      months) retraining was given and details of further reactions (frequency,
      severity and treatment) were obtained. Criteria for allocation of EpiPen were
      evaluated. RESULTS: The worst reaction pre-enrolment was mild in 64% and
      moderate/severe in 36% (airway narrowing). Of 615 subjects followed up, 21% had a
      further reaction (eightfold reduction in frequency), mostly mild. There was a 60
      fold reduction in the frequency of severe reactions. Of those with a moderate
      severe initial reaction, 99.5% had no or a less severe follow-up reaction. No
      child with a mild or severe index reaction had a severe follow-up reaction. Only
      1/615 (0.2%) had a severe follow-up reaction and only 2/615 (0.3%) used
      adrenaline, both successfully and had it available according to our criteria. Of
      mild-moderate reactions, 77% required oral antihistamines alone and 15% no
      treatment. Children who had follow-up reactions had more frequent and severe
      reactions pre-enrolment. CONCLUSION: The management plan greatly reduced the
      frequency and severity of further reactions and was successful for all children.
      Our criteria for selective prescription of EpiPen in the context of this
      management plan were appropriate. This is the first study to provide evidence on
      which to inform practice.

PMID- 15969667
TI  - Epicutaneous exposure to peanut protein prevents oral tolerance and enhances
      allergic sensitization.
AB  - BACKGROUND: Food allergies are an important cause of life-threatening
      hypersensitivity reactions. Oral tolerance can be considered the default immune
      response to dietary antigens, with immune deviation resulting in allergic
      sensitization. However, primary sensitization to food allergens may not solely be
      through the gastrointestinal mucosa, as strong T-helper type 2 (Th2)-biased
      immunity can result from exposure to protein allergens on barrier-disrupted skin.
      OBJECTIVE: The purpose of this study was to examine whether exposure to allergens
      through the skin may interfere with the normal development of oral tolerance and
      promote allergic sensitization to food proteins. METHODS: Female BALB/c mice were
      exposed epicutaneously to peanut protein and induction of systemic oral tolerance
      through high dose feeds of peanut protein was subsequently assessed. Other mice
      were rendered tolerant prior to epicutaneous peanut exposure. Sensitivity to
      peanut was determined by assessing delayed-type hypersensitivity, proliferative,
      cytokine and antibody responses. RESULTS: Epicutaneous exposure to peanut protein
      induced potent Th2-type immunity with high levels of IL-4 and serum IgE. Primary
      skin exposure prevented the subsequent induction of oral tolerance to peanut in
      an antigen-specific manner. Upon oral challenge, mice became further sensitized
      and developed strong peanut-specific IL-4 and IgE responses. Furthermore, animals
      with existing tolerance to peanut were partly sensitized following epicutaneous
      exposure. CONCLUSION: Epicutaneous exposure to peanut protein can prevent
      induction of oral tolerance, and may even modify existing tolerance to peanut.
      Epidermal exposure to protein allergens selectively drives Th2-type responses,
      and as such may promote sensitization to food proteins upon gastrointestinal
      exposure.

PMID- 15969668
TI  - The promiscuity of immunoglobulin E binding to peanut allergens, as determined by
      Western blotting, correlates with the severity of clinical symptoms.
AB  - BACKGROUND: IgE binding to a specific protein has been shown to be associated
      with severe anaphylaxis to hazelnuts; however, the relationship between IgE
      binding to specific peanut allergens and symptom severity is currently unclear.
      OBJECTIVE: To determine if the pattern of IgE binding to specific peanut
      allergens is associated with the severity of clinical symptoms. METHODS: Forty
      peanut allergic patients underwent a double-blind placebo-controlled low-dose
      peanut challenge, during which the severity of the patients' peanut allergy was
      scored. Serum peanut-specific IgE (psIgE) was measured and IgE binding patterns
      to peanut proteins analysed. RESULTS: Seventeen IgE binding bands were identified
      between 5 and 100 kDa with eight bound by >50% of patients. The total number of
      bands per patient correlated significantly with challenge score (P=0.001,
      r=0.505) and psIgE (P<0.001, r=0.820). Cluster analysis failed to reveal any
      association between a particular protein or pattern of proteins (based on
      presence/absence) and challenge score. However, two protein bands ( approximately
      43 and 41 kDa) had peak intensities that correlated positively with challenge
      score and a third band ( approximately 48 kDa) that correlated negatively. The
      bands were identified as subunits of Ara h 3/4 and 1, respectively. CONCLUSIONS:
      Promiscuity of IgE binding appears more important than the recognition of
      individual proteins. This may mean that clinically useful specific immunotherapy
      for peanut allergy will be difficult to achieve if only selected allergenic
      proteins are used. Further investigation of Ara h 1 and 3/4 subunits and a
      possible association with symptom severity are also highlighted by this study.

PMID- 15969669
TI  - Development of an in vitro system for the study of allergens and allergen
      specific immunoglobulin E and immunoglobulin G: Fcepsilon receptor I supercross
      linking is a possible new mechanism of immunoglobulin G-dependent enhancement of
      type I allergic reactions.
AB  - BACKGROUND: IgE-dependent activation of mast cells (MCs) is a key pathomechanism
      of type I allergies. In contrast, allergen-specific IgG Abs are thought to
      attenuate immediate allergic reactions by blocking IgE binding and by cross
      linking the inhibitory Fcgamma receptor IIB on MCs. OBJECTIVES: To establish a
      defined in vitro system using human MCs to study the biological activity of
      allergens and to investigate the role of allergen-specific IgE and IgG. METHODS:
      Purified human intestinal MCs sensitized with different forms of specific IgE Abs
      were triggered by monomeric and oligomeric forms of recombinant Bet v 1, the
      major birch pollen allergen, in the presence or absence of allergen-specific IgG
      Abs. Results MCs sensitized with an anti-Bet v 1 IgE mAb or sera obtained from
      birch pollen allergic patients released histamine and sulphidoleukotrienes after
      exposure to oligomeric Bet v 1. Monomeric Bet v 1 provoked mediator release only
      in MCs sensitized with patients sera but not in MCs sensitized with anti-Bet v 1
      IgE mAb. Interestingly, MC activation could be induced by supercross-linking of
      monomeric Bet v 1 bound to monovalent IgE on MCs with a secondary allergen
      specific IgG pAb. By using IgG F(ab')2 fragments we provide evidence that this
      effect is not a result of IgG binding to Fcgamma receptors. CONCLUSION: This
      assay represents a new tool for the in vitro study of MC activation in response
      to natural and genetically modified allergens. Fcepsilon receptor I supercross
      linking by allergen-specific IgG Abs provides a possible new mechanism of IgG
      dependent enhancement of type I allergic reactions.

PMID- 15969670
TI  - The mycotoxins citrinin and gliotoxin differentially affect production of the pro
      inflammatory cytokines tumour necrosis factor-alpha and interleukin-6, and the
      anti-inflammatory cytokine interleukin-10.
AB  - BACKGROUND: Microbial growth is considered one of the major causes of indoor air
      problems. Moulds have been associated with asthma, allergy and a wide range of
      diffuse indoor air-related symptoms. However, mechanisms of the adverse health
      effects are not well understood. OBJECTIVE: We hypothesized that the mycotoxins
      citrinin and gliotoxin could cause an imbalance between the secretion of the pro
      inflammatory cytokines TNF-alpha and IL-6 and the anti-inflammatory cytokine IL
      10. METHODS: We investigated the influence of citrinin and gliotoxin on the human
      monocytic cell line Mono-Mac-6 (MM6) with and without lipopolysaccharide 
      stimulation. The levels of IL-10, IL-6 and TNF-alpha were analysed in cell
      culture supernatants by ELISA. Cell viability and cell apoptosis were measured by
      flow cytometry. RESULTS: The strongest inhibition of cytokine secretion was found
      for IL-10. IL-6 levels were found to decrease in a dose-dependent manner along
      with reduced cell viability. TNF-alpha levels increased with low gliotoxin
      exposure (less than 100 ng/mL), but decreased significantly at 375 ng/mL and
      higher along with increased cell apoptosis and reduced cell viability. TNF-alpha
      levels were not reduced by citrinin exposure. CONCLUSION: We observed a cytokine
      imbalance with a more pronounced reduction of IL-10 concentrations compared with
      those of TNF-alpha and IL-6. We suggest that low exposure doses of citrinin and
      gliotoxin (corresponding to less than 100 ng/mL gliotoxin and less than 10 mug/mL
      citrinin) may inhibit IL-10 and lead to increased risk of an inflammatory
      response with relative overproduction of TNF-alpha and IL-6. The findings and
      their clinical implications must be verified by human studies. However, we
      speculate that the observed biological effects may be of importance as they may
      partly explain the occurrence of diffuse general indoor air-related symptoms as
      well as the worsening of asthmatic inflammatory reactions experienced in mouldy
      environments.

PMID- 15969671
TI  - Haplotype analysis of a 100 kb region spanning TNF-LTA identifies a polymorphism
      in the LTA promoter region that is associated with atopic asthma susceptibility
      in Japan.
AB  - BACKGROUND: The tumour necrosis factor (TNF) gene family, which includes TNF,
      LTA, and LTB, is located consecutively on human chromosome 6p21 region, which has
      been linked to asthma by several genome-wide screens. (LTA, lymphotoxin-alpha;
      LTB, lymphotoxin-beta). OBJECTIVE: The aim of the present study was to determine
      whether genes on 6q21 are related to development of atopic asthma. Methods We
      screened for mutations in the coding and promoter regions of genes in the TNF-LTA
      region, including BAT1, NFKBIL1, LTA, TNF, LTB, AIF, and BAT2, and conducted a
      transmission disequilibrium test of 41 polymorphisms in 137 families identified
      through pro-bands with childhood-onset atopic asthma. (BAT1, HLA-B-associated
      transcript 1; NFKBIL1, nuclear factor of kappa light polypeptide gene enhancer in
      B cells inhibitor-like 1; AIF, allograft inflammatory factor 1). RESULTS:
      Haplotypes of the LTA/TNF linkage disequilibrium block were associated
      significantly with asthma (global P=0.0097). Transmission patterns of the common
      haplotypes to asthmatic offspring were predicted by a single-nucleotide
      polymorphism in the LTA promoter region. The G allele of the LTA-753G/A
      polymorphism was transmitted preferentially to asthma-affected individuals
      (P=0.001). Luciferase reporter assays with constructs containing the 5' and 3'
      flanking regions of the LTA gene showed 30-50% lower transcriptional activity
      when the -753A allele was present than that of other haplotypes. CONCLUSION: Our
      results suggest that LTA is one of the genes that contributes to susceptibility
      to atopic asthma, and that the association of the TNF/LTA haplotypes to asthma
      may be defined by the polymorphism in the LTA promoter region in the Japanese
      population.

PMID- 15969672
TI  - The DR4-DQ8 haplotype and a specific T cell receptor Vbeta T cell subset are
      associated with absence of allergy to Can f 1.
AB  - BACKGROUND: The significance of specific T cell receptor (TCR) Vbeta subtypes and
      human leucocyte antigen (HLA) class II alleles for the development of allergy to
      lipocalin allergens such as the major dog allergen Can f 1 is not clear at
      present. OBJECTIVE: To characterize the TCR Vbeta usage in the Can f 1-specific T
      cell lines and the HLA class II genotypes of Can f 1-allergic and non-allergic
      subjects. METHODS: T cell lines were induced with recombinant Can f 1 from the
      peripheral blood mononuclear cells of 12 non-atopic dog owners and 26 dog
      allergic patients. Thirteen of the dog-allergic subjects were sensitized to Can f
      1. Expression of the TCR Vbeta subtypes on CD4(+) T cells in the T cell lines was
      measured by flow cytometry. The subjects were HLA genotyped for DRB1, DQB1 and
      DPB1 loci. RESULTS: Can f 1-specific T cell lines were obtained from 18 subjects,
      with either positive (n=8) or negative (n=10) skin prick tests (SPTs) to
      recombinant Can f 1. The frequency of TCR Vbeta5.1(+) T cells was significantly
      higher in the T cell lines of subjects with negative SPTs to the allergen.
      Moreover, DR4-DQ8 haplotype was over-represented among these subjects.
      CONCLUSION: The DR4-DQ8 haplotype and the TCR Vbeta5.1(+) CD4(+) T cells may be
      protective against allergy to Can f 1.

PMID- 15969673
TI  - Interleukin-4 production by human alveolar macrophages.
AB  - BACKGROUND: IL-4 is a key factor for T helper type 2 (Th2) differentiation and Ig
      class switching to IgE and IgG(4) during the development of immune responses. IL
      4 is produced by T cells, mast cells, basophils, and eosinophils. However, there
      is also evidence suggesting that rat alveolar macrophages (AMs) produce IL-4.
      OBJECTIVE: Given the importance of AMs and Th2-related diseases in the lung, we
      investigated the production of IL-4 by human AMs. METHODS: Human AMs were
      isolated from bronchoalveolar lavage, purified, and IL-4 production was
      investigated at mRNA and protein levels using real-time PCR, flow cytometry,
      immunocytochemistry, and ELISA. The presence of IL-4 was investigated in subjects
      with asthma or asymptomatic airway hyper-responsiveness, and in normal non
      smokers. RESULTS: IL-4 and IL-4delta2 (a splice variant found in other IL-4
      producing cells) mRNAs were found in all these subjects, but IL-4 expression
      could not be correlated with a particular disease. Protein production was
      verified by immunocytochemistry and flow cytometry analysis demonstrating,
      respectively, up to 69% and 59% positive AMs, regardless of the subject
      condition. Furthermore, phorbol-12-myristate-13-acetate and calcium ionophore
      stimulated the release of IL-4 after 48 h treatment in the presence of anti-IL-4
      receptor antibody. CONCLUSION: Our results show for the first time that IL-4 and
      IL-4delta2 mRNA are expressed and IL-4 protein produced and released by human
      AMs, suggesting a contribution of these cells in the modulation of Th2 immune
      response.

PMID- 15969674
TI  - The novel use of the human nasal epithelial cell line RPMI 2650 as an in vitro
      model to study the influence of allergens and cytokines on transforming growth
      factor-beta gene expression and protein release.
AB  - BACKGROUND: The epithelial accumulation of mast cells is a feature of allergic
      rhinitis and this has been linked to the expression of the known mast cell
      chemoattractant transforming growth factor-beta (TGF-beta) at this site. Little
      is known concerning the regulation of TGF-beta gene expression or protein release
      by nasal epithelial cells. To address this we have utilized the RPMI 2650 human
      nasal epithelial cell line, which has some features that closely resemble normal
      nasal epithelium and has been reported to secrete a TGF-beta-like molecule.
      OBJECTIVES: To investigate the regulation of TGF-beta gene expression and protein
      secretion in RPMI 2650 nasal epithelial cells following exposure to allergens
      (house dust mite (HDM) and grass pollen) and mast cell associated T-helper type 2
      (Th2) cytokines (IL-4, IL-13, and TNF-alpha). Methods Light and scanning electron
      microscopy was used to evaluate the morphology of RPMI 2650 cells in culture,
      enzyme-linked immunosorbent assay was used to investigate their TGF-beta
      secretory capacity and the identification of the TGF-beta isotype(s) involved,
      flow cytometry was used to demonstrate the presence of TGF-beta receptors on the
      RPMI 2650 cells, and the quantitative real-time TaqMan PCR was used to measure
      TGF-beta gene expression. RESULTS: TGF-beta(2) was identified as the main isotype
      secreted by the RPMI 2650 cells. HDM allergens and TNF-alpha increased both TGF
      beta gene expression and protein release from these cells, whereas grass pollen,
      IL-4, and IL-13 were without effect. CONCLUSIONS: The RPMI 2650 nasal epithelial
      cell line represents a valid in vitro model to evaluate the regulation of TGF
      beta biology. In this system HDM allergens have stimulatory activity that is
      fundamentally different from that of grass pollen allergens, and the Th2
      cytokines IL-4 and IL-13 are without effect. The ability of TNF-alpha to up
      regulate both TGF-beta gene expression and protein release indicates that mast
      cell-epithelial interactions concerning TGF-beta are bi-directional and this may
      be fundamental to epithelial immunoregulation. The availability of a model
      system, such as the RPMI 2650 cells, will enable the early evaluation of future
      novel and targeted interventions directed toward the aberrant responses of upper
      airway structural cells.

PMID- 15969675
TI  - Allergic airway inflammation induces tachykinin peptides expression in vagal
      sensory neurons innervating mouse airways.
AB  - BACKGROUND: Allergic airway inflammation has been shown to induce pro
      inflammatory neuropeptides such as tachykinin peptides substance P (SP) and
      neurokinin A (NKA) together with related peptide like calcitonin gene-related
      peptide (CGRP) in nodose sensory neurons innervating guinea-pig airways.
      OBJECTIVE: The present study was designed to examine the effects of allergen
      sensitization and challenge on the SP/NKA expression in the jugular-nodose
      ganglion neurons innervating the murine airways. METHODS: Using retrograde
      neuronal tracing technique in combination with double-labelling
      immunohistochemistry, the expression of SP/NKA was investigated in a murine model
      of allergic airway inflammation. RESULTS: Allergic airway inflammation was found
      to induce the expression of SP/NKA (13.2+/-1.43% vs. 5.8+/-0.37%, P<0.01) in
      large-diameter (>20 microm) vagal sensory neurons retrograde labelled with Fast
      blue dye from the main stem bronchi. CONCLUSION: Based on the induction of
      tachykinins in airway-specific large-sized jugular-nodose ganglia neurons by
      allergic airway inflammation, the present study suggests that allergen
      sensitization and challenge may lead to de novo induction of tachykinins in
      neurons. This may partly contribute to the pathogenesis of airways diseases such
      as allergic airway inflammation.

PMID- 15969676
TI  - Persistent airway hyper-responsiveness and inflammation in Toxocara canis
      infected BALB/c mice.
AB  - BACKGROUND: Infection with Toxocara canis, the roundworm of dogs, has been
      associated with asthmatic manifestations. Clinical symptoms such as wheezing,
      coughing and episodic airflow obstruction have been described for patients
      infected with this helminth. OBJECTIVE: In order to characterize the effect of T.
      canis infection on the lungs, we monitored immune responses, pulmonary pathology
      and lung function over a period of 60 days in BALB/c mice. METHODS: Infection was
      performed by a single oral administration of 1000 T. canis embryonated eggs.
      Airway responsiveness was measured in conscious, unrestrained mice at 7, 14, 30
      and 60 days post-infection (p.i.). RESULTS: Infection of mice resulted in airway
      hyper-responsiveness (AHR) that persisted up to 30 days p.i. Pulmonary
      inflammation as well as increased levels of IgE and eosinophils in
      bronchoalveolar lavage (BAL) persisted up to 60 days p.i. Cytokine analysis in
      BAL indicated increased levels of IL-5 at day 7 and 14 p.i., whereas the levels
      of IL-2, IFN-gamma, IL-4 and IL-10 did not differ from those of uninfected
      controls. Toxocara-specific stimulation of spleen cells using recombinant TES-70
      protein resulted in the induction of IL-5 at day 7 and 14 p.i. and IL-10 at day
      14 p.i. Production of all other cytokines did not differ from that of uninfected
      controls. Evaluation of larval burden revealed that T. canis was still present in
      the lungs of infected mice at 60 days p.i. CONCLUSION: The presence of Toxocara
      larva in the lungs at 60 days p.i. following a single infection could explain the
      persistent pulmonary inflammation, airway hyper-reactivity, eosinophilia and
      increased IgE production observed in T. canis-infected BALB/c mice.

PMID- 15969677
TI  - Molecular and cellular targets of anti-IgE antibodies.
AB  - Immunoglobulin E (IgE) was the last of the immunoglobulins discovered. It is
      present in very low amounts (nano- to micro-gram per ml range) in the serum of
      normal healthy individuals and normal laboratory mouse strains and has a very
      short half-life. This contrasts with the other immunoglobulin classes, which are
      present in much higher concentrations (micro- to milligram per ml range) and form
      a substantial component of serum proteins. Immunoglobulins play a role in
      homeostatic mechanisms and they represent the humoral arm of defence against
      pathogenic organisms. Since IgE antibodies play a key role in allergic disorders,
      a number of approaches to inhibit IgE antibody production are currently being
      explored. In the recent past the use of nonanaphylactic, humanized anti-IgE
      antibodies became a new therapeutic strategy for allergic diseases. The
      therapeutic rational beyond the idea derives from the ability of the anti-IgE
      antibodies to bind to the same domains on the IgE molecule that interact with the
      high-affinity IgE receptor, thereby interfering with the binding of IgE to this
      receptor without cross-linking the IgE on the receptor (nonanaphylactic anti-IgE
      antibodies). Treatment with anti-IgE antibodies leads primarily to a decrease in
      serum IgE levels. As a consequence thereof, the number of high-affinity IgE
      receptors on mast cells and basophils decreases, leading to a lower excitability
      of the effector cells reducing the release of inflammatory mediator such as
      histamine, prostaglandins and leukotrienes. Experimental studies in mice indicate
      that injection of some monoclonal anti-IgE antibodies also inhibited IgE
      production in vivo. The biological mechanism behind this reduction remains
      speculative. A possible explanation may be that these antibodies can also
      interact with membrane bound IgE on B cells, which could interfere the IgE
      production.

PMID- 15969678
TI  - CD4CD25 regulatory T lymphocytes in allergy and asthma.
AB  - Allergic asthma is characterized by airway hyper-responsiveness and chronic
      mucosal inflammation mediated by CD4(+) Th2 lymphocytes. Regulatory CD4(+)CD25(+)
      T cells are important components of the homeostasis of the immune system, as
      impaired CD4(+)CD25(+) T cell activity can cause autoimmune diseases and allergy.
      The mechanism of suppression by CD4(+)CD25(+) T cells remains controversial;
      different in vivo and in vitro studies raise possible roles for the
      immunosuppressive cytokines interleukin-10 and transforming growth factor-beta,
      forkhead transcription factor Foxp3, glucocorticoid-induced tumor necrosis factor
      receptor, cytotoxic lymphocyte associated antigen-4, 4-1BB costimulator receptor,
      a CD4-related molecule LAG-3, and neuropilin-1. Current data suggest that Th2
      responses to allergens are normally suppressed by CD4(+)CD25(+) T cells.
      Suppression by CD4(+)CD25(+) T cells is decreased in allergic individuals.
      Furthermore, CD4(+)CD25(+) T cells play a key role in regulating airway
      eosinophilic inflammation. The immunomodulatory properties of CD4(+)CD25(+) T
      cells do extend to Th2 responses, most notably by limiting the development of a
      proinflammatory CD4(+) Th2 phenotype characterized by reduced cytokine
      production. An understanding of the roles of CD4(+)CD25(+) T cells in vivo could
      provide better insight into the design of novel approaches to modulate the
      chronic airway inflammatory reaction evident in bronchial asthma.

PMID- 15969679
TI  - A framework for measuring costs to society of IgE-mediated food allergy.
AB  - Both immunoglobulin E (IgE)-mediated food allergy and food intolerance can lead
      to many changes in personal behaviour and health care resource use which have
      important economic consequences. These costs will impact directly, indirectly and
      intangibly on both individuals and society in general. It is important to measure
      the cost of illness (COI) of food allergy as a first step in developing and
      evaluating measures to reduce and control the burden of illness. This paper
      outlines a framework for assessing COI of food allergy from different viewpoints.
      It offers a structure for identifying the different cost impacts on allergic and
      nonallergic consumers, food producers and society as a whole, and for scoping,
      measurement and valuation of relevant costs. Within this structure, the existing
      literature is reviewed. This review illustrates the lack of information and clear
      methodology for assessing costs of food allergy. The paper concludes that there
      is a need for a more structured research programme to generate data essential for
      future evaluations of procedures and technologies for the diagnosis, treatment
      and management of food allergy.

PMID- 15969680
TI  - Allergic bronchopulmonary aspergillosis.
AB  - Allergic bronchopulmonary aspergillosis (ABPA) occurs in nonimmunocompromised
      patients and belongs to the hypersensitivity disorders induced by Aspergillus.
      Genetic factors and activation of bronchial epithelial cells in asthma or cystic
      fibrosis are responsible for the development of a CD(4)+Th2 lymphocyte activation
      and IgE, IgG and IgA-AF antibodies production. The diagnosis of ABPA is based on
      the presence of a combination of clinical, biological and radiological criteria.
      The severity of the disease is related to corticosteroid-dependant asthma or/and
      diffuse bronchiectasis with fibrosis. The treatment is based on oral
      corticosteroids for 6-8 weeks at acute phase or exacerbation and itraconazole is
      now recommended and validated at a dose of 200 mg/day for a duration of 16 weeks.

PMID- 15969681
TI  - Worm infestation and the negative association with eczema (atopic/nonatopic) and
      allergic sensitization.
AB  - BACKGROUND: Worm infestations may play a role in preventing allergies. There is a
      lack of epidemiological information from Western countries on the association
      between worm infestation and eczema. OBJECTIVE: To investigate the association
      between worm infestation and eczema in a proper temporal sequence and under
      consideration of allergic sensitization. METHODS: Two surveys were performed in
      East German school children. Questionnaire data included the history of eczema
      and worm infestation and their time of onset. Specific IgE antibodies to five
      common aeroallergens were measured and used to define nonatopic and atopic
      eczema. Logistic regression analyses were performed to control for relevant
      confounders (age, sex, parental school education and history of allergies). In
      order to confirm the findings a corresponding conditional regression analysis was
      applied on cases and controls matched by age and sex. RESULTS: A total of 4169
      children participated (response 75 and 76%) who were, on average, 9.2 years old
      (47% girls). Overall 17.0% reported a prior worm infestation (Ascaris 44%,
      Oxyuris 33%) and 18.1% had a history of eczema. Eczema occurred significantly
      less frequent in children who had a worm infestation (prior to the onset of
      eczema) compared with children without such a history (8.1%vs 16.5%, OR(adj):
      0.45, 95% CI: 0.33-0.60). The finding was confirmed by the corresponding matched
      case-control analysis (OR(adj): 0.57, 95% CI: 0.41-0.79). Atopic eczema was
      affected more by a prior worm infestation (OR(adj): 0.31, 95% CI: 0.18-0.56) than
      the nonatopic eczema (OR(adj): 0.58, 95% CI: 0.40-0.84). A total of 29.1%
      exhibited specific IgE antibodies to at least one aeroallergen. Sensitized
      children gave significantly less frequent a history of worm infestation (14.2%vs
      18.3%, OR(adj): 0.74, 95% CI: 0.60-0.92). Stratified analysis revealed that this
      effect most pronounced for a sensitization to house dust mite. CONCLUSIONS: A
      worm infestation is associated with a reduced frequency of subsequent eczema,
      especially the atopic type. Furthermore allergic sensitization, especially to
      house dust mite, and worm infestation are negatively associated. The data support
      the concept that a lack of immune-stimulation by parasitic infections contributes
      to the development of allergies.

PMID- 15969682
TI  - Development of a functional in vitro assay as a novel tool for the
      standardization of allergen extracts in the human system.
AB  - BACKGROUND: Biochemical and immunochemical methods used for batch control of
      allergen extracts rely on the binding of IgE molecules to allergens. They do not
      measure the ability of a protein to induce type I allergic reactions. Therefore,
      a biological assay was established that is based on the cellular mechanisms of
      allergies in order to assess the cross-linking capacity of allergens. METHODS:
      Rat basophilic leukaemia cells were transfected with cDNA coding for the human
      high affinity IgE receptor chains. The surface expression of the IgE-binding
      alpha-chain was detected by FACS analysis and the functional integration of the
      'humanized' receptors into the signal transduction cascade was addressed by
      intracellular calcium mobilization. Mediator release was measured in response to
      human IgE and a variety of cross-linking allergen preparations. RESULTS: Several
      clones were obtained that were able to bind allergen-specific human IgE. The
      results of the biological assay were compared with those obtained by
      immunochemical methods. The biological assay was used to determine the potency of
      allergen extracts, including highly diluted products that cannot be analysed by
      conventional methods. CONCLUSION: A stable 'humanized' basophil cell line was
      established that will be a useful tool for the standardization and batch control
      of allergen extracts. Because of its high sensitivity, it can also be used to
      detect minute quantities of potentially allergenic proteins, e.g. in processed
      foods. In addition, the test may support the development of novel allergy
      vaccines, such as recombinant hypoallergenic molecules.

PMID- 15969683
TI  - Coincidence of atopy profile in terms of monosensitization and polysensitization
      in children and their parents.
AB  - BACKGROUND: Results from epidemiologic studies have shown that childhood atopy is
      probably a hereditary disorder, because the offspring of affected parents have a
      higher risk of developing atopy. Among the atopic population, some subjects are
      sensitized to only one class of allergens (monosensitized), while other subjects
      are sensitized to more than one class of allergens (polysensitized). The aim of
      this study was to investigate whether atopy profile
      (monosensitization/polysensitization) in children is linked to the same
      conditions in their parents. METHODS: We evaluated sensitization to five classes
      of aeroallergens (house dust mites, animal danders, pollens, molds, and
      cockroach) by skin prick testing in a group of 494 children with suspicious
      allergic symptoms and in their parents. RESULTS: The frequency of parental atopy
      was highest (51.6%) in polysensitized children (n = 189), intermediate (37.1%) in
      monosensitized children (n = 178), and was lowest (22.4%) in nonsensitized
      children (n = 127). The proportion of polysensitized subjects among atopic
      parents was significantly higher for polysensitized children (45.6%) than for
      monosensitized children (31.1%). Polysensitized children were found to more
      frequently have one or both parents polysensitized (32.3%, 7.4%) than
      monosensitized children (18.5%, 2.2%) with odds ratios of 2.09 (95% CI: 1.29
      3.40) and 3.48 (1.12-10.78), respectively, whereas the likelihood of having one
      or two monosensitized parents was not increased for polysensitized children.
      CONCLUSION: Our data suggest a familial coincidence of atopy profile in terms of
      monosensitization and polysensitization, although the relative importance of
      genetic or environmental influence should be studied further.

PMID- 15969685
TI  - Mutations in the high-affinity IgE receptor beta-chain are not associated with
      nonresponder status.
AB  - BACKGROUND: Basophils of some individuals do not release histamine upon
      activation of their high-affinity immunoglobulin E (IgE) receptor
      (Fc(epsilon)RI), but do so if this receptor is circumvented for cell activation.
      This so-called nonresponder phenomenon is clinically relevant, because in various
      studies atopy was less frequent or absent in nonresponder individuals. So far, it
      is unknown if this phenomenon is acquired during adulthood or exists from birth
      on. METHODS: Histamine release was determined from isolated leucocytes stimulated
      with anti-IgE or calciumionophor. Also, random primed cDNA was synthesized and
      the open reading frame (ORF) of the Fc(epsilon)RI beta-subunit amplified and
      sequenced. RESULTS: In the first part of our study, we examined the role of
      atopic status, type of atopy, and age in a random population of 95 children of
      whom we found 22% to be nonresponder. None of these parameters correlated with
      the nonresponder status. Except for food allergy, no specific type of atopy
      correlated with histamine release. The mechanism underlying the nonresponder
      phenomenon is assumed to occur early in the signalling cascade. We hypothesized
      that mutations in the Fc(epsilon)RI beta-chain may be associated with the
      nonresponder status, and in the second part of our study sequenced the beta
      subunit in 20 responders and 20 nonresponders. Two conservative and two
      nonconservative heterozygous one base mutations (Thr179Thr, Asp216Asp, Ile147Leu
      and Glu237Gly) were found in two nonresponders and one responder. Three of these
      mutations have not been described so far. CONCLUSION: The nonresponder phenomenon
      is present from birth on and genetically determined. In our population, it was
      not associated with age or the presence of atopy, and appeared not to be caused
      by mutations in the Fc(epsilon)RI beta-chain.

PMID- 15969684
TI  - Utility of the ratio of food-specific IgE/total IgE in predicting symptomatic
      food allergy in children.
AB  - BACKGROUND: Double-blind, placebo-controlled food challenges are time-consuming,
      expensive and not without risk to patients. Therefore, an in vitro test that
      could accurately diagnose food allergy would be of great value. OBJECTIVE: To
      evaluate the utility of the ratio of specific immunoglobulin E (IgE)/total IgE
      compared with specific IgE (sIgE) alone in predicting symptomatic food allergy.
      METHODS: We retrospectively analysed 992 controlled oral food challenges
      performed in 501 children (median age 13 months). The ratio of sIgE/total IgE was
      calculated and tested for correlation with the outcome of food challenges.
      Receiver operator characteristics (ROC)-curves were performed; predicted
      probabilities and predictive decision points were calculated. RESULTS: A
      significant correlation was found between the ratio and the outcome of food
      challenges for cow's milk (CM), hen's egg (HE), and wheat, but not for soy. The
      ROC and predicted probability curves as well as sensitivity and specificity of
      the decision points of the ratio were similar to those of sIgE levels for CM, HE
      and wheat. CONCLUSION: In view of the greater effort needed to determine the
      ratio, without benefit compared with the sIgE alone, the calculation of the ratio
      of sIgE/total IgE for diagnosing symptomatic food allergy offers no advantage for
      CM, HE, wheat or soy. For the majority of cases controlled oral food challenges
      still remain the method of choice.

PMID- 15969686
TI  - Gene expression and regulation of transcription factor activator protein-2 alpha
      in human mast cells.
AB  - BACKGROUND: The transcription factor activator protein (AP)-2 regulates cell-type
      specific gene expression during development and differentiation, but its role in
      mast cell development has so far not been explored. METHODS: Gene expression and
      regulation of AP2 was assessed in normal skin, diseases with increased mast cell
      numbers, and in vitro models of mast cell differentiation. RESULTS: AP-2alpha
      protein was not detectable in normal skin but in mastocytoma lesional mast cells.
      AP-2alpha-mRNA and -protein were also detected in leukemic mast cells (HMC-1), in
      the adherent fraction of peripheral blood (PBMC) and umbilical cord blood
      mononuclear cells (CBMC), and AP-2alpha-mRNA at low levels in isolated-purified
      mast cells. During culture with fibroblast supernatants or SCF, AP-2alpha-mRNA
      was de novo expressed in KU812-cells, maintained at about the same level in PBMC
      and CBMC, and upregulated in HMC-1-cells. On extended culture, a down-regulation
      was noted at mRNA and/or protein levels. In contrast, tryptase expression
      increased in all cells throughout culture, as did c-Kit in normal cells, whereas
      in both leukemic cell lines, c-Kit was maintained unchanged at about the same
      level. CONCLUSIONS: These findings suggest a continuous activation of AP-2alpha
      in mastocytomas and mast cell leukemia and its transient upregulation during c
      Kit dependent early steps of normal mast cell differentiation.

PMID- 15969687
TI  - Relationships between specific serum IgE, cytokines and polymorphisms in the IL
      4, IL-4Ralpha in patients with penicillins allergy.
AB  - BACKGROUND: Excessive production of interleukin (IL)-4, IL-13 and interferon
      (IFN)-gamma is thought to be important in the development of allergic disease and
      atopy. Several investigators have linked the IL-4 and IL-4R genes to allergic
      disease and atopy. The aim of this study is to further explore the mechanism of
      penicillins allergy and evaluate the possible role of the IL-4 C-589T and IL
      4RalphaQ576R polymorphisms in modulating the allergic responses to penicillins.
      METHODS: Radioallergosorbent test (RAST) was used to detect eight kinds of
      specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL-4, IL
      13 and IFN-gamma were measured by using enzyme-linked immunosorbent assay
      (ELISA). The IL-4 C-589T and IL-4RalphaQ576R polymorphisms were genotyped by
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: Compared with control subjects, there were significantly higher levels
      of IL-4, IL-13 and IFN-gamma in allergic patients with positive specific IgE (P <
      0.01), and the lower levels of IL-4 and IFN-gamma were observed in allergic
      patients with negative specific IgE (P < 0.05). We found a growing trend of IL-4
      and IL-13 levels with the kind increasing of positive specific IgE, and even
      there were significant correlations between the three kinds of cytokines and many
      kinds of specific IgE (P < 0.05). The IL-4Ralpha*Q576 allele was significantly
      increased in patients with penicillins allergy compared with control subjects (P
      < 0.01). Furthermore, the allele was strongly associated with increased serum
      specific benzylpenicilloyl (BPO)-, phenoxomethylpenicillanyl (PVA)- or
      ampicillanyl (APA)-IgE levels in patients with positive specific IgE (P < 0.05).
      CONCLUSIONS: These data suggest that IL-4, IL-13 and IFN-gamma play an important
      roles in penicillins allergy. The IL-4RalphaQ576R polymorphism may involve in the
      development of penicillins allergy, and through modulating specific serum IgE
      levels.

PMID- 15969688
TI  - Dog factor differences in Can f 1 allergen production.
AB  - BACKGROUND: The clinical importance of dog allergy is well known, but it is
      unknown if all types of dogs represent the same risk for allergic patients. The
      purpose of this work was to evaluate among 288 healthy dogs if the levels of Can
      f 1 on fur vary between breeds (German Shepherd, Pyrenean Shepherd, Poodle,
      Cocker spaniel, Spaniel, Griffon, Labrador retriever and Yorkshire terrier),
      gender, hormonal status, hair length, and according to the presence of seborrhea.
      METHODS: Each dog was shaved in a limited area and Can f 1 concentrations were
      measured in mug/g fur by ELISA. The results (geometric mean values and 95%
      confidence intervals) were analyzed using analysis of variance and with
      nonparametric tests. RESULTS: A wide variability in Can f 1 levels was found
      between dog breeds, from Labradors [1.99 (0.03-129.91)] to Yorkshires [16.72
      (3.67-76.16)] and Poodles [17.04 (2.79-103.94)] but only the Labrador levels were
      significantly different from each other breed. Males produced more Can f 1 than
      females, 11.75 (1.27-108.40) vs 8.89 (0.91-86.39). No difference was found
      according to hair length or hormonal status. The seborrheic status highly (P =
      0.0019) influenced the presence of Can f 1 on hair: 16.66 (1.59-173.96) vs 9.40
      (1.03-85.70). CONCLUSION: Breeds (Labrador retriever), sex and seborrhea seem to
      influence the levels of Can f 1 on fur.

PMID- 15969689
TI  - Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and
      bronchoalveolar eosinophilia induced by an allergic reaction.
AB  - BACKGROUND: Allergic reactions occur through the exacerbated induction of a Th2
      cell type expression profile and can be prevented by agents favoring a Th1
      profile. Bacillus Calmette-Guerin (BCG) is able to induce high IFN-gamma levels
      and has been shown to decrease experimentally induced allergy. The induction of
      IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon
      mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL
      12. OBJECTIVE: We evaluated the ability of a recombinant BCG strain producing IL
      18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)
      dependent allergic reaction. METHODS: Mice were injected intraperitoneally or
      intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at
      days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received
      OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant
      BCG. RESULTS: A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1
      and IgG2a levels indicated no significant difference between the three groups of
      mice. However, following in vitro stimulation with OVA, lymph node cells from
      rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice
      injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge,
      a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected
      mice compared to the nontreated or nonrecombinant BCG-treated groups. CONCLUSION:
      These results indicate that the production of IL-18 by rBCG may enhance the
      immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in
      particular, decrease airway eosinophilia.

PMID- 15969690
TI  - A new tool to evaluate the impact of chronic urticaria on quality of life:
      chronic urticaria quality of life questionnaire (CU-QoL).
AB  - BACKGROUND: Health-related quality of Life in patients with chronic urticaria is
      evaluated by mean of generic instruments or questionnaire designed for skin
      diseases. No disease-specific tool is now available for the assessment of chronic
      urticaria impact from patients' viewpoint. OBJECTIVE: The aim of our study is to
      develop and validate a new questionnaire specifically designed for the assessment
      of quality of life in chronic urticaria (Chronic Urticaria Quality of Life
      Questionnaire -- CU-Q(2)oL). METHODS: In the development phase of CU-Q(2)oL an
      initial list of items of 37 items was compiled and given to 80 patients with
      chronic urticaria; the 23 most significant items were selected and converted into
      questions evaluating the answers on a Likert scale of five steps. The validation
      procedure involved 125 patients (86 F and 39 M) (age 42.17 +/- 9.24 years).
      RESULTS: Following a statistical analysis, CU-Q(2)oL showed a six-dimensional
      structure and good levels of internal consistency for the extracted factors:
      Pruritus (0.79), Swelling (0.65), Impact on life activities (0.83), Sleep
      problems (0.77), Looks (0.83) and Limits (0.74). In stable conditions CU-Q(2)oL
      showed a good reliability, ranged between 0.64 and 0.92. Responsiveness to
      clinical changes was accomplished. DISCUSSION: These results provide evidence
      that CU-Q(2)oL has specificity enough for being a valid tool for detecting the
      relative burden of CU on subjective wellbeing, and for obtaining a global
      evaluation both of CU impact and of treatments, taking into account the patient's
      point of view. The CU-Q(2)oL was easily and quickly filled up and well accepted
      by the patients.

PMID- 15969691
TI  - Are house dust mite allergen levels influenced by cold winter weather?
AB  - BACKGROUND: Moisture is vitally important for house dust mites and they cannot
      survive in cold or hot-dry climates. AIMS OF THE STUDY: To investigate the
      influence of two extraordinarily cold and dry winters in 1995/1996 and 1996/1997
      on house dust mite levels in German homes. METHODS: Dust samples were collected
      between June 1995 and December 2001 on the mattresses of 655 adults and 454
      schoolchildren living in five different areas of Germany. We compared house dust
      mite allergen Dermatophagoides pteronyssinus (Der p 1) levels before and during
      the winters of 1995/1996 and 1996/1997 with levels after these winters. RESULTS:
      D. pteronyssinus (Der p 1) levels in samples taken after the cold winters of
      1995/1996 and 1996/1997 were approximately two times lower than Der p 1 levels in
      dust samples collected before or during these respective winters (Geometric
      means: Erfurt 89 vs 33 ng/g; Hamburg 333 vs 219 ng/g; Bitterfeld, Hettstedt, and
      Zerbst 296 vs 180 ng/g). Except for Hamburg, the decrease in Der p 1 levels was
      statistically significant. D. pteronyssinus levels measured in dust samples
      collected in 2001 (i.e. 3 years after the two cold winters) show a statistically
      non-significant increase (Geometric means: Erfurt 33 vs 39 ng/g; Hamburg 219 vs
      317 ng/g), suggesting that it may take a long time for mite allergen levels to
      increase again after a sudden decrease. CONCLUSION: We conclude that Der p 1
      levels in German mattress dust samples have been approximately reduced by a
      factor of three to four by the two consecutive cold winters of 1995/1996 and
      1996/1997.

PMID- 15969692
TI  - La mano de DIOS...was the PIAMA intervention study intervened upon?
AB  - The PIAMA study evaluates whether application of mite impermeable mattress covers
      reduces exposure to mite allergen sufficiently to reduce the incidence of asthma
      and mite allergy. The study started in 1996. Baseline measurements of mite
      allergen levels were conducted on mattresses of newborn children and their
      parents, mostly in 1997. Mite allergen levels were surprisingly low in this study
      compared with previous studies among school children and infants. Mite allergen
      levels were measured again on mattresses in the PIAMA study in the years
      2000/2001 when the children were 4 years old, and in a new study among 6-12 year
      old school children conducted in the fall of 2001. Data on winter climate were
      collected as well. In the winters of 1995/1996 and 1996/1997, which preceded and
      coincided with the PIAMA baseline measurements, temperatures had been extremely
      low, and precipitation had been extremely low as well. It is likely that these
      unusual winter weather conditions affected the baseline allergen levels in the
      PIAMA study so that the effect of the planned intervention (mite impermeable
      mattress covers) was considerably smaller than it could have been.

PMID- 15969693
TI  - Allergy to lansoprazole: study of cross-reactivity among proton-pump inhibitors.

PMID- 15969694
TI  - Anaphylaxis after a horse bite.

PMID- 15969695
TI  - The place of spirometry in the diagnosis of asthma in those suffering from
      allergic rhinitis: a pilot study.

PMID- 15969696
TI  - Allergy due to Ensis macha.

PMID- 15969697
TI  - Plasma concentration of TARC/CCL17 is elevated in nonepisodic angioedema
      associated with eosinophilia.

PMID- 15969698
TI  - Moth plant (Araujia sericifera) allergy.

PMID- 15969699
TI  - Eligibility for long-term care in The Netherlands: development of a decision
      support system.
AB  - In The Netherlands, eligibility for subsidised long-term care services is
      assessed by regional governmental assessment agencies. We examined which factors
      predict eligibility for eight long-term care alternatives, ranging from a variety
      of arrangements for care at home to admissions to residential and nursing homes.
      Data were drawn from the records of a sample of the regional assessment agencies,
      mostly during the year 2000. The model shows that not only disease and disability
      but also age, household composition, current housing situation, and use of health
      care services determine the choice between the long-term care alternatives. On
      the basis of this model, we developed a decision support system. This system
      predicts eligibility for long-term care alternatives on the basis of applicant
      characteristics, and can support needs assessors in making decisions on the
      eligibility of individual applicants. It is used for standardization of intake
      processes and development of protocols for needs assessors. At the population
      level, it may provide information for managers and policy-makers on the
      distribution of demand for long-term care in the near future.

PMID- 15969700
TI  - Intellectual disability, challenging behaviour and cost in care accommodation:
      what are the links?
AB  - The paper examines the links between degree of intellectual disability,
      challenging behaviour, service utilisation and cost for a group of people with
      intellectual disabilities living in care accommodation in England. A cross
      sectional survey was conducted of people with intellectual disabilities,
      identified via provider organisations, with supplementary collection of costs
      data. Multivariate analyses of cost variations were carried out for 930 adults
      with intellectual disabilities. There were strong, nonlinear, interdependent
      links between degree of intellectual disability, behaviour, service use and
      costs. Higher costs were associated with more severe intellectual disabilities
      and more challenging behaviour. Sector and scale of residence also influenced
      cost in quite complex ways. Access to and use of services by people with
      intellectual disabilities were not always appropriately linked to perceived or
      actual needs. Policy makers and local commissioning agencies need to explore the
      sources of cost variation between individuals, sectors and types of accommodation
      in order to achieve national policy objectives on quality, choice, independence
      and inclusion.

PMID- 15969701
TI  - A prospective baseline study of frail older people before the introduction of an
      intermediate care service.
AB  - This paper describes the first part of a two-stage research project designed to
      investigate the clinical and service outcomes of a comprehensive intermediate
      care service. It is a baseline study of patients presenting to two elderly care
      departments as emergencies with the clinical syndromes of falls, incontinence,
      confusion or poor mobility before the introduction of a city-wide intermediate
      care service. The outcome measures were: mortality; disability (Barthel Index,
      BI); social activities (Nottingham Extended Activities of Daily Living); service
      use; and carer distress (General Health Questionnaire -28). These were measured
      at 3, 6 and 12 months after recruitment. Eight hundred and twenty-three patients
      were recruited (median age = 84 years; proportion of women = 70%; proportion with
      cognitive impairment = 45%; median BI score = 15). There was a high mortality
      rate (36%), evidence for incomplete recovery, a gradual decline in independence
      over 12 months and a high degree of carer stress. There was little use of
      rehabilitation services (< 5%), about 25% required readmission to hospital by
      each assessment point and there was a gradual increase in institutional care
      admissions. These findings support a needs-based argument for a more
      comprehensive community service for frail older people.

PMID- 15969702
TI  - Recruitment of religious organisations into a community-based health promotion
      programme.
AB  - Programmes concerned with health promotion activities frequently rely on
      community organisations to deliver health behaviour change interventions. This
      paper presents data on the recruitment of religious organisations (ROs) into a
      research project focused on dietary change. The authors contacted the membership
      list of a local multi-denominational religious umbrella organisation by mail. The
      recruitment process consisted of a screening survey followed by an informational
      meeting with RO representatives, with additional meetings as necessary. The ROs
      were surveyed by telephone, and the initial and follow-up meetings were held at a
      location convenient to the RO representatives, often the RO's building. For this
      paper, the unit of analysis is the RO. The ROs approached during the recruitment
      process were of a variety of faiths and denominations. All were located within
      the metropolitan area of Seattle, WA, USA. The screening survey was used to
      determine RO eligibility, and collect further information on the RO and its
      membership. The survey included questions adapted from previous RO surveys and
      questions developed by the project team. The recruitment strategy yielded a 26%
      enrollment rate of eligible ROs. In comparison to eligible ROs, those that did
      not meet the eligibility criteria were less stable, smaller and had a membership
      that was less white, less college-educated and more working class. The size of
      the RO and the number of years that the religious leader had been with the RO
      were the strongest predictors of the RO's interest in participating in the
      project. These data will be helpful in recruiting community organisations into
      health promotion programmes.

PMID- 15969703
TI  - Assessing the educational needs of community sexual healthcare practitioners.
AB  - There is wide variation in the quality and nature of community sexual health
      service delivery in the UK, which has led to a number of professional and
      Government-led directives to improve service provision. One key target is the
      provision of appropriate training and updating of staff in order to maintain an
      appropriate skill level. To identify the educational development needs of
      community sexual health nursing and medical staff, preparatory to commissioning
      appropriate educational provision, a training needs analysis survey was
      conducted. This involved using a customised psychometrically valid and reliable
      instrument, which was administered to all relevant staff for self-completion.
      Fifty-four (67.5%) of all doctors and nurses working in a community sexual health
      directorate responded. For the whole sample, the following categories of
      development need were identified: professional development; research; legal
      issues; clinical practice; and communication/interpersonal skills. When the
      nursing and medical subsamples were analysed separately, the same generic
      training needs emerged, although the nurses and doctors identified 22 and 25
      significant training needs, respectively. The reported skills deficits cluster
      into super-ordinate groups which resonate with other available literature. This
      suggests that each category could be reliably used to inform a short course or
      series of modules, either for the whole sample or for each professional group.
      The results also suggest that the instrument is viable for use with healthcare
      professionals working in this specialty. Consequently, if this approach to
      identifying skill deficits was adopted, limited educational budgets could be used
      to provide courses which would meet the real training needs of staff, and if
      offered as a shared learning opportunity, could promote multidisciplinary team
      working. In this way, improved local healthcare provision could be readily
      realised, with the potential for reducing current variations in the quality of
      community sexual health provision.

PMID- 15969704
TI  - Parenting support in the context of poverty: a meta-synthesis of the qualitative
      evidence.
AB  - From the outset, providing support for parents has been a key feature of New
      Labour's policy agenda, but 'good' parenting, and child health and well-being are
      often undermined by the stresses associated with poverty. Moreover, there may be
      a gap between policy aims, and the perceptions and motivations of those intended
      to benefit. Drawing on a systematic review of qualitative studies of low-income
      parents, the present paper explores their experiences of informal and formal
      support networks, considering their strengths and weaknesses in the context of
      poverty. Traditional systematic review methods were used to locate and critically
      appraise 12 UK qualitative studies, which took as their focus parents' subjective
      experiences of caring for children in impoverished circumstances. Meta
      ethnographic methods were then used to produce a qualitative meta-synthesis of
      findings. Exploring the similarities and differences in parents' accounts across
      studies identified positive and negative aspects of social support as a resource
      for poor parents. The review suggests that naturally occurring support systems do
      provide both material and emotional help to parents, but that such support has
      certain inherent drawbacks. It is not universally available and, in some
      circumstances, carries negative associations for poor families. Low-income lone
      mothers in particular enjoy smaller support networks, and are more reliant on
      mutual support than those in two-parent families. Paradoxically, it is the most
      socially isolated women who are least willing to seek professional help. Overall,
      low-income parents' experiences of formal health and social welfare agencies are
      mixed, and not invariably positive. In conclusion, this paper suggests that
      formal support services have the potential to fill gaps in informal support
      systems for poor families, but only if these are provided in ways which are
      sensitive to their needs. Therefore, parents' perspectives are essential to
      informing service design, development and evaluation in health and social care.

PMID- 15969705
TI  - Support workers in intermediate care.
AB  - Despite the proliferation of support worker roles in the UK, little is known
      about their actual numbers, employment conditions or levels of training.
      Intermediate care services appear to be an important employer of support workers,
      but the diversity of intermediate care services makes the task of understanding
      support worker roles even more complex. This paper presents data from 33 services
      which were involved in an NHS Modernisation Agency's Changing Workforce Programme
      project, the Accelerated Development Programme for Support Workers in
      Intermediate Care in England. Within this project, the main employers of support
      workers were primary care trusts and/or social services. Participating
      intermediate care teams were involved in admission avoidance, assisted discharge
      and reablement, or combinations of these services, and the majority of care was
      provided in the patient's own home. The 33 services employed 794 support workers
      and 368 professionally qualified staff. The mean ratio of professionally
      qualified staff to support workers was 0.95 (range = 0-4.9, SD = 1.05). Support
      worker roles included multidisciplinary working, meeting rehabilitation needs,
      providing personal care and enablement. Team leaders included nurses, social
      workers, physiotherapists, professional managers, home carers and support
      workers. The most commonly reported sources of support worker training were
      National Vocational Qualifications and in-house training. In 80% of the services,
      at least half of the support workers had a qualification. Three models of
      supervision emerged across the services: the allocation of a mentor; team
      supervision; and formal and informal line management. These findings illustrate
      the diversity of employment of support workers in intermediate care. The
      variations in training, supervision and skill mix have implications for clinical
      governance and support worker regulation. The employment of support worker staff
      jointly across health and social care raises cross-boundary issues around
      employment contracts and pay.

PMID- 15969706
TI  - 'I daresay I might find it embarrassing': general practitioners' perspectives on
      discussing sexual health issues with lesbian and gay patients.
AB  - The present paper explores general practitioners' (GPs') perspectives on the
      difficulties which they face when discussing sexual health issues with lesbian
      and gay patients in primary care consultations. It draws upon data obtained from
      a qualitative interview study with 22 GPs aged between 34 and 57 years who were
      practising in Sheffield, UK. Interviews were transcribed verbatim and the data
      were analysed thematically. The results indicate that (non-hetero)sexual
      orientation could form a barrier to talking about sexual health matters for
      almost half of this GP sample. Difficulties related primarily to ignorance of
      lesbian and gay lifestyles and sexual practices, and also included concerns about
      the appropriate language to use and assumptions about the nature of gay men's
      relationships. Homophobic attitudes were also identified in a minority of the
      sample. Participants suggested improvements around improving communication about
      sexual health with lesbian and gay patients. These included training at
      undergraduate and postgraduate levels, taking a proactive role during
      consultations, not making assumptions about patients' sexual orientation and
      having a non-discriminatory policy for their practice.

PMID- 15969707
TI  - Dementia care provision in rural Scotland: service users' and carers'
      experiences.
AB  - There has been global neglect of service users' and carers' experiences of
      dementia care provision in rural areas. The present paper draws on a qualitative
      study of service provision for people with dementia and their carers in remote
      and rural Scotland. It draws on interviews with 15 people with dementia and 16
      carers to explore their views about health and social dementia care service
      provision in rural Scotland. A further 14 carers of people with dementia
      participated in one of three focus groups. The paper discusses perceived gaps in
      services as well as positive aspects of dementia service provision which service
      users attribute to living in a rural area. The important issues this raises for
      the development of dementia care provision in rural areas are briefly discussed.

PMID- 15969708
TI  - According to need? Predicting the amount of municipal home help allocated to
      elderly recipients in an urban area of Sweden.
AB  - Given the cutbacks which have been carried out in the Swedish welfare state
      despite the unchanged official policy of allocation of home help services
      according to needs, it is essential to evaluate the factors which guide the
      allocation of home help today. Whereas numerous studies have identified factors
      which predict entry into the home help system, the present paper concentrates on
      predictors of the amount of home help amongst those allocated assistance. Data
      were obtained from the population-based care and services section of the 2002
      Swedish National Study of Aging and Care-Kungsholmen (SNAC-K). All home help
      recipients (> or = 65 years of age) living in an inner city district of Stockholm
      (Kungsholmen) were analysed with ordinary least squares regressions to identify
      predictors of the number of hours of home help (n = 943). Need indicators, i.e.
      dependency in activities of daily living (ADLs) and instrumental ADLs (IADLs),
      and cognitive impairment (Berger scale) were the strongest predictors of more
      hours of home help. The addition of sociodemographic (i.e. age, gender and
      income), environmental (i.e. informal care, housing adaptations and housing
      accessibility) and structural (i.e. variations in allocation decisions between
      one care manager and another) factors contributed only marginally to the
      explained variance. Hours of help entitlement increased slightly with greater
      age. Co-residing individuals were allocated significantly fewer home help hours
      than those living alone. Income and regular access to informal care were not
      significant predictors. The fact that services are provided according to need
      criteria does not necessarily mean that the provided services are adequate to
      meet needs. On the macro level, social policy decisions and available economic
      and manpower resources determine the allotment of municipal home help. However,
      this study in an urban sample suggests that, within the available resources, the
      amount of home help allocated is guided mainly by need indicators amongst those
      given assistance.

PMID- 15969709
TI  - Sea change or quick fix? Policy on long-term conditions in England.
AB  - Long-term conditions is a policy area that has risen rapidly up the political
      agenda in England, culminating in the development of the National Health Service
      and Social Care Model in 2005, which is to be implemented over the following 2
      years. The Model draws heavily upon US ideas of case management and proposes the
      creation of 3000 community matrons to undertake this role with the most
      vulnerable patients. Although welcomed in principle, the specific proposals in
      the Model have been subject to some criticism, and these issues are explored in
      the present paper. The problematic areas include patient identification, the
      transplanting of US models to England, the role of case management, workforce and
      funding issues, and the mix of medical and social models. The author concludes
      that there is a danger of long-term care policy developing an unduly health
      focused approach at a time when the thrust of partnership working is towards an
      inclusive, whole-system model.

PMID- 15969711
TI  - Molecular ecology of parasites: elucidating ecological and microevolutionary
      processes.
AB  - We review studies that have used molecular markers to address ecological and
      microevolutionary processes in parasites. Our goal is to highlight areas of
      research that may be of particular interest in relation to the parasitic
      lifestyle, and to draw attention to areas that require additional study. Topics
      include species identification, phylogeography, host specificity and speciation,
      population genetic structure, modes of reproduction and transmission patterns,
      and searching for loci under selection.

PMID- 15969712
TI  - Patterns of vegetative growth and gene flow in Rhizopogon vinicolor and R.
      vesiculosus (Boletales, Basidiomycota).
AB  - We have collected sporocarps and tuberculate ectomycorrhizae of both Rhizopogon
      vinicolor and Rhizopogon vesiculosus from three 50 x 100 m plots located at
      Mary's Peak in the Oregon Coast Range (USA); linear map distances between plots
      ranged from c. 1 km to c. 5.5 km. Six and seven previously developed
      microsatellite markers were used to map the approximate size and distribution of
      R. vinicolor and R. vesiculosus genets, respectively. Genetic structure within
      plots was analysed using spatial autocorrelation analyses. No significant
      clustering of similar genotypes was detected in either species when redundant
      samples from the same genets were culled from the data sets. In contrast, strong
      clustering was detected in R. vesiculosus when all samples were analysed, but not
      in R. vinicolor. These results demonstrate that isolation by distance does not
      occur in either species at the intraplot sampling scale and that clonal
      propagation (vegetative growth) is significantly more prevalent in R. vesiculosus
      than in R. vinicolor. Significant genetic differentiation was detected between
      some of the plots and appeared greater in the more clonal species R. vesiculosus
      with Phi(ST) values ranging from 0.010 to 0.078*** than in R. vinicolor with
      Phi(ST) values ranging from -0.002 to 0.022** (*P < 0.05, **P < 0.01, ***P <
      0.001). When tested against the null hypothesis of no relationship between
      individuals, parentage analysis detected seven likely parent/offspring pairs in
      R. vinicolor and four in R. vesiculosus (alpha = 0.001). Of these 11 possible
      parent/offspring pairs, only two R. vinicolor pairs were still supported as
      parent/offspring when tested against the alternative hypothesis of being full
      siblings (alpha = 0.05). In the latter two cases, parent and offspring were
      located at approximately 45 m and 28 m from each other. Challenges to parentage
      analysis in ectomycorrhizal fungi are discussed.

PMID- 15969713
TI  - High diversity of oilseed rape pollen clouds over an agro-ecosystem indicates
      long-distance dispersal.
AB  - Abstract Estimating the frequency of long-distance pollination is important in
      cultivated species, particularly to assess the risk of gene transfer following
      the release of genetically modified crops. For this purpose, we estimated the
      diversity and origin of fertilizing pollen in a 10 x 10 km French oilseed rape
      production area. First, the cultivar grown in each field was identified through
      surveys to farmers and using microsatellite markers. Examination of the seed set
      in fields indicated high rates of seed contamination (8.7%) and pollination from
      other sources (5%). Then, male-sterile plants were scattered over the study area
      and their seed genotyped using the same markers. Most pollination was local: 65%
      of the seeds had a compatible sire in the closest field, i.e. at 50 or 300 m
      depending on site, but the nearest compatible field was found more than 1000 m
      away for 13% of the seeds. To assess the diversity of fertilizing pollen, each
      seed was assigned to the nearest putative siring cultivar. The observed diversity
      of pollen was then compared to that predicted by simulations using three
      empirical dispersal models with increasing proportion of long-distance
      pollination. The diversity was sensitive to the dispersal kernel used in the
      simulations, fatter-tailed functions predicting higher diversities. The dispersal
      kernel that was more consistent with our data predicted more long-distance
      dispersal than the exponential function.

PMID- 15969714
TI  - Phylogeography, genetic structure, and diversity in the dhole (Cuon alpinus).
AB  - The Asiatic wild dog or dhole was once very widely distributed across Asia but
      now has a very fragmented range. In this first genetic study of this little-known
      species, we obtained information on genetic diversity, phylogeography, and social
      structure using both mitochondrial control region sequencing and microsatellite
      genotyping of noninvasive faecal samples from wild populations, as well as from
      museum and captive samples. A pattern largely consistent with isolation by
      distance across the Asian mainland was observed, with no clear subspecies
      distinctions. However, two major phylogeographical groupings were found across
      the mainland, one extending from South, Central, and North India (south of the
      Ganges) into Myanmar, and the other extending from India north of the Ganges into
      northeastern India, Myanmar, Thailand and the Malaysian Peninsula. We propose a
      scenario involving glaciation events that could explain this pattern. The origin
      of the dhole populations in Sumatra and Java is enigmatic and requires further
      study. Very low levels of genetic diversity were observed among wild dholes from
      Baluran National Park in Java, Indonesia, but in contrast, high levels were
      observed in Mudumalai Wildlife Sanctuary in South India.

PMID- 15969715
TI  - Age, phylogeography and population structure of the microendemic banded spring
      snail, Mexipyrgus churinceanus.
AB  - Recent theoretical and empirical studies of phylogeography and population
      structure indicate that many processes influence intraspecific evolutionary
      history. The present study represents the first examination of various forces
      influencing the spatial and temporal patterns of sequence variation in the
      freshwater Mexican banded spring snail, Mexipyrgus churinceanus. This snail
      occurs in one of the most critically endangered centres of freshwater endemism,
      the desert ecosystem of Cuatro Cienegas. From cytochrome b mtDNA sequence
      variation, there is strong evidence of long-term isolation of three regions,
      suggesting that these regions represent evolutionarily distinct lineages.
      Molecular clock estimates of clade age indicate a time to most recent common
      ancestor of approximately 2.5 million years ago (Ma). The three regions differ
      considerably in the historical and demographic forces affecting population
      structure. The western populations have extremely low mtDNA diversity consistent
      with a severe bottleneck dating to 50,000 years before present (bp). The nearby
      Rio Mesquites drainage is characterized by fragmentation events, restricted gene
      flow with isolation by distance, and higher levels of mtDNA polymorphism. These
      patterns are consistent with the long-term stability of this drainage along with
      habitat heterogeneity and brooding contributing to population isolation and
      restricted gene flow. Southeastern populations show evidence of range expansion
      and a strong influence of genetic drift. Migration rates between drainages
      indicate very little gene flow between drainages except for asymmetric migration
      from the Rio Mesquites into both western and southeastern drainages.

PMID- 15969716
TI  - The mtDNA catalogue of all Portuguese autochthonous goat (Capra hircus) breeds:
      high diversity of female lineages at the western fringe of European distribution.
AB  - Goat is believed to be the first true livestock domesticated and, apart from its
      historical importance, keeps playing an essential economic role in very diverse
      human societies. We have analysed the female gene pool of all Portuguese
      autochthonous breeds (Bravia, Serrana, Charnequeira, Serpentina and Algarvia)
      through the mtDNA HVI sequencing of 288 unrelated animals sampled throughout the
      country. All breeds proved to be extremely diverse (average haplotype diversity
      of 0.977), in contrast with the Portuguese peripheral geographic situation in the
      distribution range of the species. Moreover, observed genetic distances between
      breeds do not correlate with microgeography inside Portugal. These observations
      are consistent with recurrent refreshment of the breeding stock through the
      introduction of exotic animals. Fitting the new data into the still loosely
      defined female genetic pool landscape of goats, all Portuguese animals, one
      sample excepted (belonging to Bravia), are classified into haplogroup A and
      haplotype sharing is geographically very sparse, including a Far East match. Our
      results confirm that goats stand out among most of domesticates as exceptionally
      diverse and showing an unparalleled degree of mobility of animals (at least
      females) used for reproductive purposes.

PMID- 15969717
TI  - Regeneration mode affects spatial genetic structure of Nothofagus dombeyi
      forests.
AB  - Disturbance may generate population bottlenecks by reducing population size and
      the number of founders establishing a new colony. We tested the hypothesis that
      the scale of disturbance affects the levels of genetic diversity and the spatial
      distribution of genotypes in naturally regenerating stands of Nothofagus dombeyi,
      an evergreen angiosperm tree, in northwestern Patagonia. At similar spatial
      scales, we predicted that old-growth stands characterized by fine-scale gap phase
      dynamics would be genetically diverse due to restricted gene flow among temporal
      and spatially isolated gaps. In contrast, young massively regenerated postfire
      cohorts resulting from coarse-scale disturbances would be genetically more
      homogeneous. At each of three paired old-growth and postfire stands a minimum of
      50 trees were mapped and sampled within 1 ha. Fresh tissue was collected for
      isozyme analysis from a total of 361 trees along with tree cores and diameters.
      Tree age distributions reflected the dominant modes of regeneration. Six out of
      nine analysed loci were polymorphic. Mean genetic diversity parameters were
      greater but not significant in mature stands. Fixation indices suggested
      significant heterozygous deficit at two-thirds of possible tests indicating a
      Wahlund effect due to local recruitment of related seeds. F(ST) indicated
      moderate between-stand divergence. Mature stands concentrated half of positively
      like joins and yielded significant (P < 0.05) autocorrelation coefficients at
      small distance classes (< 20 m). Fine-scale patch dynamics within mature stands
      favours the maintenance of fine-scale genetic structure as a result of shade
      intolerance and local seed dispersal. Conversely, postfire stands suffer the
      effects of genetic drift given that a few reproductive trees produce a somewhat
      impoverished and genetically uniform progeny. Bottleneck effects will depend upon
      the density of remnant trees which could also be a function of the severity of
      fire.

PMID- 15969718
TI  - Invasion of Lepidium draba (Brassicaceae) in the western United States:
      distributions and origins of chloroplast DNA haplotypes.
AB  - Advances in phylogeography are of great value for understanding the population
      structure and origins of invasive genotypes. Such insights provide constructive
      information for current or future biological control research efforts. In this
      study, we investigated a highly variable chloroplast DNA (cpDNA) marker for
      populations of the weed Lepidium draba (Brassicaceae) in its native Eurasian and
      invasive US ranges. We sequenced DNA from 684 individuals from Eurasia and the US
      and found 41 different haplotypes. Our comparative study between the native and
      invasive ranges showed a 33% reduction in allelic richness (A) and a 7% reduction
      in haplotype diversity (h) since introduction into the US. Most genetic variation
      in the native range was observed within geographical regions and populations, not
      between regions, and this result was similar for the invasive range. Assignment
      tests indicated the most likely origins of many invasive haplotypes. Some of
      these occurred in western Europe, supporting an expanded native range that had
      been proposed for the species. Exact locations were identified for a diverse set
      of invasive haplotypes which can be used in ongoing host-specificity tests of
      potential biological control agents.

PMID- 15969719
TI  - Conservation genomics: disequilibrium mapping of domestic cattle chromosomal
      segments in North American bison populations.
AB  - Introgressive hybridization is one of the major threats to species conservation,
      and is often induced by human influence on the natural habitat of wildlife
      species. The ability to accurately identify introgression is critical to
      understanding its importance in evolution and effective conservation management
      of species. Hybridization between North American bison (Bison bison) and domestic
      cattle (Bos taurus) as a result of human activities has been recorded for over
      100 years, and domestic cattle mitochondrial DNA was previously detected in bison
      populations. In this study, linked microsatellite markers were used to identify
      domestic cattle chromosomal segments in 14 genomic regions from 14 bison
      populations. Cattle nuclear introgression was identified in five populations,
      with an average frequency per population ranging from 0.56% to 1.80%. This study
      represents the first use of linked molecular markers to examine introgression
      between mammalian species and the first demonstration of domestic cattle nuclear
      introgression in bison. To date, six public bison populations have been
      identified with no evidence of mitochondrial or nuclear domestic cattle
      introgression, providing information critical to the future management of bison
      genetic resources. The ability to identify even low levels of introgression
      resulting from historic hybridization events suggests that the use of linked
      molecular markers to identify introgression is a significant development in the
      study of introgressive hybridization across a broad range of taxa.

PMID- 15969720
TI  - Microsatellite analyses reveal fine-scale genetic structure in grey mouse lemurs
      (Microcebus murinus).
AB  - Information on genetic structure can be used to complement direct inferences on
      social systems and behaviour. We studied the genetic structure of the solitary
      grey mouse lemur (Microcebus murinus), a small, nocturnal primate endemic to
      western Madagascar, with the aim of getting further insight on its breeding
      structure. Tissue samples from 167 grey mouse lemurs in an area covering 12.3 km2
      in Kirindy Forest were obtained from trapping. The capture data indicated a
      noncontinuous distribution of individuals in the study area. Using 10
      microsatellite markers, significant genetic differentiation in the study area was
      demonstrated and dispersal was found to be significantly male biased.
      Furthermore, we observed an overall excess of homozygotes in the total population
      (F(IT) = 0.131), which we interpret as caused by fine-scale structure with
      breeding occurring in small units. Evidence for a clumped distribution of
      identical homozygotes was found, supporting the notion that dispersal distance
      for breeding was shorter than that for foraging, i.e. the breeding neighbourhood
      size is smaller than the foraging neighbourhood size. In conclusion, we found a
      more complex population structure than what has been previously reported in
      studies performed on smaller spatial scales. The noncontinuous distribution of
      individuals and the effects of social variables on the genetic structure have
      implications for the interpretation of social organization and the planning of
      conservation activities that may apply to other solitary and endangered mammals
      as well.

PMID- 15969721
TI  - Conservation genetics and population history of the threatened European mink
      Mustela lutreola, with an emphasis on the west European population.
AB  - In species of great conservation concern, special attention must be paid to their
      phylogeography, in particular the origin of animals for captive breeding and
      reintroduction. The endangered European mink lives now in at least three well
      separated populations in northeast, southeast and west Europe. Our aim is to
      assess the genetic structure of these populations to identify 'distinct
      population segments' (DPS) and advise captive breeding programmes. First, the
      mtDNA control region was completely sequenced in 176 minks and 10 polecats. The
      analysis revealed that the western population is characterized by a single mtDNA
      haplotype that is closely related to those in eastern regions but nevertheless,
      not found there to date. The northeast European animals are much more variable
      (pi = 0.012, h = 0.939), with the southeast samples intermediate (pi = 0.0012, h
      = 0.469). Second, 155 European mink were genotyped using six microsatellites. The
      latter display the same trends of genetic diversity among regions as mtDNA [gene
      diversity and allelic richness highest in northeast Europe (H(E) = 0.539, R(S) =
      3.76), lowest in west Europe (H(E) = 0.379, R(S) = 2.12)], and provide evidences
      that the southeast and possibly the west populations have undergone a recent
      bottleneck. Our results indicate that the western population derives from a few
      animals which recently colonized this region, possibly after a human
      introduction. Microsatellite data also reveal that isolation by distance occurs
      in the western population, causing some inbreeding because related individuals
      mate. As genetic data indicate that the three populations have not undergone
      independent evolutionary histories for long (no phylogeographical structure),
      they should not be considered as distinct DPS. In conclusion, the captive
      breeding programme should use animals from different parts of the species'
      present distribution area.

PMID- 15969722
TI  - Conservation implications of complex population structure: lessons from the
      loggerhead turtle (Caretta caretta).
AB  - Complex population structure can result from either sex-biased gene flow or
      population overlap during migrations. Loggerhead turtles (Caretta caretta) have
      both traits, providing an instructive case history for wildlife management. Based
      on surveys of maternally inherited mtDNA, pelagic post-hatchlings show no
      population structure across the northern Atlantic (phi(ST) < 0.001, P = 0.919),
      subadults in coastal habitat show low structure among locations (phi(ST) = 0.01,
      P < 0.005), and nesting colonies along the southeastern coast of the United
      States have strong structure (phi(ST) = 0.42, P < 0.001). Thus the level of
      population structure increases through progressive life history stages. In
      contrast, a survey of biparentally inherited microsatellite DNA shows no
      significant population structure: R(ST) < 0.001; F(ST) = 0.002 (P > 0.05) across
      the same nesting colonies. These results indicate that loggerhead females home
      faithfully to their natal nesting colony, but males provide an avenue of gene
      flow between regional nesting colonies, probably via opportunistic mating in
      migratory corridors. As a result, all breeding populations in the southeastern
      United States have similar levels of microsatellite diversity (H(E) = 0.70-0.89),
      whereas mtDNA haplotype diversity varies dramatically (h = 0.00-0.66). Under a
      conventional interpretation of the nuclear DNA data, the entire southeastern
      United States would be regarded as a single management unit, yet the mtDNA data
      indicate multiple isolated populations. This complex population structure
      mandates a different management strategy at each life stage. Perturbations to
      pelagic juveniles will have a diffuse impact on Atlantic nesting colonies,
      mortality of subadults will have a more focused impact on nearby breeding
      populations, and disturbances to adults will have pinpoint impact on
      corresponding breeding populations. These findings demonstrate that surveys of
      multiple life stages are desirable to resolve management units in migratory
      marine species.

PMID- 15969723
TI  - Diversity of algal endosymbionts (zooxanthellae) in octocorals: the roles of
      geography and host relationships.
AB  - The presence, genetic identity and diversity of algal endosymbionts
      (Symbiodinium) in 114 species from 69 genera (20 families) of octocorals from the
      Great Barrier Reef (GBR), the far eastern Pacific (EP) and the Caribbean was
      examined, and patterns of the octocoral-algal symbiosis were compared with
      patterns in the host phylogeny. Genetic analyses of the zooxanthellae were based
      on ribosomal DNA internal transcribed spacer 1 (ITS1) region. In the GBR samples,
      Symbiodinium clades A and G were encountered with A and G being rare. Clade B
      zooxanthellae have been previously reported from a GBR octocoral, but are also
      rare in octocorals from this region. Symbiodinium G has so far only been found in
      Foraminifera, but is rare in these organisms. In the Caribbean samples, only
      Symbiodinium clades B and C are present. Hence, Symbiodinium diversity at the
      level of phylogenetic clades is lower in octocorals from the Caribbean compared
      to those from the GBR. However, an unprecedented level of ITS1 diversity was
      observed within individual colonies of some Caribbean gorgonians, implying either
      that these simultaneously harbour multiple strains of clade B zooxanthellae, or
      that ITS1 heterogeneity exists within the genomes of some zooxanthellae.
      Intracladal diversity based on ITS should therefore be interpreted with caution,
      especially in cases where no independent evidence exists to support
      distinctiveness, such as ecological distribution or physiological
      characteristics. All samples from EP are azooxanthellate. Three unrelated GBR
      taxa that are described in the literature as azooxanthellate (Junceella fragilis,
      Euplexaura nuttingi and Stereonephthya sp. 1) contain clade G zooxanthellae, and
      their symbiotic association with zooxanthellae was confirmed by histology. These
      corals are pale in colour, whereas related azooxanthellate species are brightly
      coloured. The evolutionary loss or gain of zooxanthellae may have altered the
      light sensitivity of the host tissues, requiring the animals to adopt or reduce
      pigmentation. Finally, we superimposed patterns of the octocoral-algal symbiosis
      onto a molecular phylogeny of the host. The data show that many losses/gains of
      endosymbiosis have occurred during the evolution of octocorals. The ancestral
      state (azooxanthellate or zooxanthellate) in octocorals remains unclear, but the
      data suggest that on an evolutionary timescale octocorals can switch more easily
      between mixotrophy and heterotrophy compared to scleractinian corals, which
      coincides with a low reliance on photosynthetic carbon gain in the former group
      of organisms.

PMID- 15969724
TI  - Out of Cuba: overwater dispersal and speciation among lizards in the Anolis
      carolinensis subgroup.
AB  - Overwater dispersal and subsequent allopatric speciation contribute importantly
      to the species diversity of West Indian Anolis lizards and many other island
      radiations. Here we use molecular phylogenetic analyses to assess the
      contribution of overwater dispersal to diversification of the Anolis carolinensis
      subgroup, a clade comprising nine canopy-dwelling species distributed across the
      northern Caribbean. Although this clade includes some of the most successful
      dispersers and colonists in the anole radiation, the taxonomic status and origin
      of many endemic populations have been ambiguous. New mitochondrial and nuclear
      DNA sequences from four species occurring on small islands or island banks
      (Anolis brunneus, Anolis longiceps, Anolis maynardi, Anolis smaragdinus) and one
      species from the continental United States (A. carolinensis) are presented and
      analysed with homologous sequences sampled from related species on Cuba (Anolis
      allisoni and Anolis porcatus). Our analyses confirm that all five non-Cuban
      species included in our study represent distinct, independently evolving lineages
      that warrant continued species recognition. Moreover, our results support Ernest
      Williams's hypothesis that all of these species originated by overseas
      colonization from Cuban source populations. However, contrary to Williams's
      hypothesis of Pleistocene dispersal, most colonization events leading to
      speciation apparently occurred earlier, in the late Miocene-Pliocene. These
      patterns suggest that overwater dispersal among geologically distinct islands and
      island banks is relatively infrequent in anoles and has contributed to allopatric
      speciation. Finally, our results suggest that large Greater Antillean islands
      serve as centres of origin for regional species diversity.

PMID- 15969725
TI  - Phylogeography of Balkan wall lizard (Podarcis taurica) and its relatives
      inferred from mitochondrial DNA sequences.
AB  - Wall lizards of the genus Podarcis (Sauria, Lacertidae) comprise 17 currently
      recognized species in southern Europe, where they are the predominant reptile
      group. The taxonomy of Podarcis is complex and unstable. Based on DNA sequence
      data the species of Podarcis falls into four main groups that have substantial
      geographical conherence (western island group, southwestern group, Italian group
      and Balkan group). The Balkan species are divided in two subgroups: the subgroup
      of Podarcis taurica (P. taurica, P. milensis, P. gaigeae and perhaps P.
      melisellensis), and the subgroup of Podarcis erhardii (P. erhardii and P.
      peloponnesiaca). We addressed the question of phylogenetic relations among the
      species of the P. taurica subgroup encountered in Greece, as they can be inferred
      from partial mtDNA (cyt b and 16S) sequences. Our data support the monophyly of
      P. taurica subgroup and suggest that P. gaigeae, P. milensis and P. melisellensis
      form a clade, which thereinafter connects to P. taurica. Within the previous
      clade, P. gaigeae is more closely related to P. milensis than to P.
      melisellensis. However, the specimens of P. taurica were subdivided in two
      different groups. The first one includes the specimens from northeastern Greece,
      and the other group includes the specimens from the rest of continental Greece
      and Ionian islands. Because the molecular clock of the cyt b and 16 rRNA genes
      was not rejected in our model test, it is possible to estimate times of
      speciation events. Based on the splitting of the island of Crete from
      Peloponnisos [c. 5 million years ago (Ma)], the evolutionary rate for the cyt b
      is 1.55% per million years (Myr) and for the 16S rRNA is 0.46% per Myr. These
      results suggest that the evolutionary history of P. taurica in Greece is more
      complex than a single evolutionary invasion. The data analysed, stress the need
      for a reconsideration of the evolutionary history of Greek Podarcis species and
      help overcome difficulties that classical taxonomy has encountered at both the
      species level.

PMID- 15969726
TI  - A mitogenic view on the evolutionary history of the Holarctic freshwater gadoid,
      burbot (Lota lota).
AB  - Climatic oscillations during the Pleistocene epoch had a dramatic impact on the
      distribution of biota in the northern hemisphere. In order to trace glacial
      refugia and postglacial colonization routes on a global scale, we studied
      mitochondrial DNA sequence variation in a freshwater fish (burbot, Lota lota;
      Teleostei, Gadidae) with a circumpolar distribution. The subdivision of burbot in
      the subspecies Lota lota lota (Eurasia and Alaska) and Lota lota maculosa (North
      America, south of the Great Slave Lake) was reflected in two distinct
      mitochondrial lineages (average genetic distance is 2.08%). The lota form was
      characterized by 30 closely related haplotypes and a large part of its range
      (from Central Europe to Beringia) was characterized by two widespread ancestral
      haplotypes, implying that transcontinental exchange/migration was possible for
      cold-adapted freshwater taxa in recent evolutionary time. However, the derived
      mitochondrial variants observed in peripheral populations point to a recent
      separation from the core group and postglacial recolonization from distinct
      refugia. Beringia served as refuge from where L. l. lota dispersed southward into
      North America after the last glacial maximum. Genetic variation in the maculosa
      form consisted of three mitochondrial clades, which were linked to at least three
      southern refugia in North America. Two mitochondrial clades east of the
      Continental Divide (Mississippian and Missourian clades) had a distinct
      geographical distribution in the southern refuge zones but intergraded in the
      previously glaciated area. The third clade (Pacific) was exclusively found west
      of the Continental Divide.

PMID- 15969727
TI  - Invasion from the cold past: extensive introgression of mountain hare (Lepus
      timidus) mitochondrial DNA into three other hare species in northern Iberia.
AB  - Mitochondrial DNA introgression from Lepus timidus into Lepus granatensis and
      Lepus europaeus was recently reported in Iberia, although L. timidus presumably
      retreated from this region at the end of the last ice age. Here we assess the
      extent of this ancient mtDNA introgression by RFLP analysis of 695 specimens
      representing the three hare species present in Iberia. The introgressed L.
      timidus lineage was found in 23 of the 37 populations sampled. It is almost fixed
      in L. europaeus across its Iberian range in the Pyrenean foothills, and in L.
      granatensis, which occupies the rest of the peninsula, it is predominant in the
      north and gradually disappears further south. We also found it in Lepus
      castroviejoi, a species endemic to Cantabria. Multiple hybridizations and,
      potentially, a selective advantage for the L. timidus lineage can explain the
      remarkable taxonomic and geographical range of this mitochondrial introgression.

PMID- 15969728
TI  - Mitochondrial haplotypes and the New Zealand origin of clonal European
      Potamopyrgus, an invasive aquatic snail.
AB  - The small aquatic snail Potamopyrgus antipodarum is an important invading species
      in Europe, Australia and North America. European populations are generally
      believed to derive from accidental introductions from New Zealand, probably
      dating back to the mid-19th century. We have employed mitochondrial DNA sequences
      to test the proposed New Zealand origin of European Potamopyrgus, and to learn
      more about its genealogical history. Using a 481-bp region of the 16S ribosomal
      RNA gene, we identified 17 distinct haplotypes among 65 snails from New Zealand.
      In marked contrast, only two haplotypes were found across all European samples,
      which cover a large geographical area. Importantly, these two haplotypes are
      shared with snails from the North Island of New Zealand. Due to sampling
      limitations we cannot rule out a South Island origin for one of the haplotypes,
      but our results clearly demonstrate the New Zealand origin of European
      populations. The marked divergence among the two European haplotypes implies the
      successful colonization by two distinct mitochondrial lineages, which is
      consistent with previous data based on nuclear markers.

PMID- 15969729
TI  - Phylogeography of two European newt species--discordance between mtDNA and
      morphology.
AB  - The newts Triturus vulgaris and Triturus montandoni are sister species that
      exhibit contrasting levels of intraspecific morphological variation. Triturus
      vulgaris has a broad Eurasiatic distribution encompassing both formerly glaciated
      and unglaciated areas and shows substantial morphological differentiation in the
      southern part of its range, while T. montandoni, confined to the Carpathians, is
      morphologically uniform. We analysed sequence variation of two mtDNA fragments of
      the total length of c. 1850 bp in 285 individuals of both species collected from
      103 localities. Phylogenetic analysis of 200 unique haplotypes defined 12 major
      clades, their age estimated at c. 4.5-1.0 million years (Myr). Most of the older
      clades were found in the southern part of the range, and also in central Europe,
      mainly in Romania. The distribution of mtDNA clades points to the existence of
      several glacial refugia, located in the Caucasus region, Anatolia, the Balkan
      Peninsula, Italy, and more to the north in central Europe. The concordance
      between mtDNA based phylogeny and the distribution of T. vulgaris subspecies was
      weak. Triturus montandoni haplotypes did not form a monophyletic group. Instead
      they were found in six clades, in five of them mixed with T. vulgaris haplotypes,
      most likely as a result of past or ongoing hybridization and multiple
      introgression of mtDNA from T. vulgaris to T. montandoni. Patterns of sequence
      variation within clades suggested long-term demographic stability in the southern
      groups, moderate and relatively old demographic growth in the populations
      inhabiting central Europe, and high growth in some of the groups that colonized
      northern parts of Europe after the last glacial maximum.

PMID- 15969730
TI  - Development of anonymous cDNA microarrays to study changes to the Senecio floral
      transcriptome during hybrid speciation.
AB  - Interspecific hybridization is an important process through which abrupt
      speciation can occur. In recent years, genetic changes associated with hybrid
      speciation have been identified through a variety of techniques, including
      AFLP/SSR mapping, GISH/FISH and cDNA-AFLP differential display. However, progress
      in using microarray technology to analyse whole genome/transcriptome changes
      associated with hybrid speciation has been limited due to the lack of extensive
      sequence data for many hybrid species and the difficulties in extrapolating
      results from commercially available microarrays for model species onto nonmodel
      hybrid taxa. Increasingly therefore researchers studying nonmodel systems are
      turning to the development of 'anonymous' cDNA microarrays, where the time and
      cost of producing microarrays is reduced by printing unsequenced cDNA clones, and
      sequencing only those clones that display interesting expression patterns. Here
      we describe the creation, testing and preliminary use of anonymous cDNA
      microarrays to study changes in floral transcriptome associated with
      allopolyploid speciation in the genus Senecio. We report a comparison of gene
      expression between the allohexaploid hybrid, Senecio cambrensis, its parental
      taxa Senecio squalidus (diploid) and Senecio vulgaris (tetraploid), and the
      intermediate triploid (sterile) hybrid Senecioxbaxteri. Anonymous microarray
      analysis revealed dramatic differences in floral gene expression between these
      four taxa and demonstrates the power of this technique for studies of the genetic
      impact of hybridization in nonmodel flowering plants.

PMID- 15969731
TI  - Genetic structure in a solitary rodent (Ctenomys talarum): implications for
      kinship and dispersal.
AB  - The genetic structure of a population provides critical insights into patterns of
      kinship and dispersal. Although genetic evidence of kin structure has been
      obtained for multiple species of social vertebrates, this aspect of population
      biology has received considerably less attention among solitary taxa in which
      spatial and social relationships are unlikely to be influenced by kin selection.
      Nevertheless, significant kin structure may occur in solitary species,
      particularly if ecological or life history traits limit individual vagility. To
      explore relationships between genetic structure, kinship, and dispersal in a
      solitary vertebrate, we compared patterns of genetic variation in two
      demographically distinct populations of the talar tuco-tuco (Ctenomys talarum), a
      solitary species of subterranean rodent from Buenos Aires Province, Argentina.
      Based on previous field studies of C. talarum at Mar de Cobo (MC) and Necochea
      (NC), we predicted that natal dispersal in these populations is male biased, with
      dispersal distances for males and females being greater at NC. Analyses of 12
      microsatellite loci revealed that in both populations, kin structure was more
      apparent among females than among males. Between populations, kinship and genetic
      substructure were more pronounced at MC. Thus, our findings were consistent with
      predicted patterns of dispersal for these animals. Collectively, these results
      indicate that populations of this solitary species are characterized by
      significant kin structure, suggesting that, even in the absence of sociality and
      kin selection, the spatial distributions and movements of individuals may
      significantly impact patterns of genetic diversity among conspecifics.

PMID- 15969732
TI  - Parentage versus two-generation analyses for estimating pollen-mediated gene flow
      in plant populations.
AB  - Assessment of contemporary pollen-mediated gene flow in plants is important for
      various aspects of plant population biology, genetic conservation and breeding.
      Here, through simulations we compare the two alternative approaches for measuring
      pollen-mediated gene flow: (i) the NEIGHBORHOOD model--a representative of
      parentage analyses, and (ii) the recently developed TWOGENER analysis of pollen
      pool structure. We investigate their properties in estimating the effective
      number of pollen parents (N(ep)) and the mean pollen dispersal distance (delta).
      We demonstrate that both methods provide very congruent estimates of N(ep) and
      delta, when the methods' assumptions considering the shape of pollen dispersal
      curve and the mating system follow those used in data simulations, although the
      NEIGHBORHOOD model exhibits generally lower variances of the estimates. The
      violations of the assumptions, especially increased selfing or long-distance
      pollen dispersal, affect the two methods to a different degree; however, they are
      still capable to provide comparable estimates of N(ep). The NEIGHBORHOOD model
      inherently allows to estimate both self-fertilization and outcrossing due to the
      long-distance pollen dispersal; however, the TWOGENER method is particularly
      sensitive to inflated selfing levels, which in turn may confound and suppress the
      effects of distant pollen movement. As a solution we demonstrate that in case of
      TWOGENER it is possible to extract the fraction of intraclass correlation that
      results from outcrossing only, which seems to be very relevant for measuring
      pollen-mediated gene flow. The two approaches differ in estimation precision and
      experimental efforts but they seem to be complementary depending on the main
      research focus and type of a population studied.

PMID- 15969733
TI  - Field studies on the environmental fate of the Cry1Ab Bt-toxin produced by
      transgenic maize (MON810) and its effect on bacterial communities in the maize
      rhizosphere.
AB  - Field studies were done to assess how much of the transgenic, insecticidal
      protein, Cry1Ab, encoded by a truncated cry1Ab gene from Bacillus thuringiensis
      (Bt), was released from Bt-maize MON810 into soil and whether bacterial
      communities inhabiting the rhizosphere of MON810 maize were different from those
      of the rhizosphere of nontransgenic maize cultivars. Bacterial community
      structure was investigated by SSCP (single-strand conformation polymorphism) of
      PCR-amplified 16S rRNA genes from community DNA. Using an improved extraction and
      detection protocol based on a commercially available ELISA, it was possible to
      detect Cry1Ab protein extracted from soils to a threshold concentration of 0.07
      ng/g soil. From 100 ng of purified Cry1Ab protein added per gram of soil, only an
      average of 37% was extractable. At both field sites investigated, the amount of
      Cry1Ab protein in bulk soil of MON810 field plots was always lower than in the
      rhizosphere, the latter ranging from 0.1 to 10 ng/g soil. Immunoreactive Cry1Ab
      protein was also detected at 0.21 ng/g bulk soil 7 months after harvesting, i.e.
      in April of the following year. At this time, however, higher values were found
      in residues of leaves (21 ng/g) and of roots (183 ng/g), the latter corresponding
      to 12% of the Cry1Ab protein present in intact roots. A sampling 2 months later
      indicated further degradation of the protein. Despite the detection of Cry1Ab
      protein in the rhizosphere of MON810 maize, the bacterial community structure was
      less affected by the Cry1Ab protein than by other environmental factors, i.e. the
      age of the plants or field heterogeneities. The persistence of Cry1Ab protein
      emphasizes the importance of considering post-harvest effects on nontarget
      organisms.

PMID- 15969734
TI  - Landscape genetics of the blotched tiger salamander (Ambystoma tigrinum
      melanostictum).
AB  - The field of landscape genetics has great potential to identify habitat features
      that influence population genetic structure. To identify landscape correlates of
      genetic differentiation in a quantitative fashion, we developed a novel approach
      using geographical information systems analysis. We present data on blotched
      tiger salamanders (Ambystoma tigrinum melanostictum) from 10 sites across the
      northern range of Yellowstone National Park in Montana and Wyoming, USA. We used
      eight microsatellite loci to analyse population genetic structure. We tested
      whether landscape variables, including topographical distance, elevation, wetland
      likelihood, cover type and number of river and stream crossings, were correlated
      with genetic subdivision (F(ST)). We then compared five hypothetical dispersal
      routes with a straight-line distance model using two approaches: (i) partial
      Mantel tests using Akaike's information criterion scores to evaluate model
      robustness and (ii) the BIOENV procedure, which uses a Spearman rank correlation
      to determine the combination of environmental variables that best fits the
      genetic data. Overall, gene flow appears highly restricted among sites, with a
      global F(ST) of 0.24. While there is a significant isolation-by-distance pattern,
      incorporating landscape variables substantially improved the fit of the model
      (from an r2 of 0.3 to 0.8) explaining genetic differentiation. It appears that
      gene flow follows a straight-line topographic route, with river crossings and
      open shrub habitat correlated with lower F(ST) and thus, decreased
      differentiation, while distance and elevation difference appear to increase
      differentiation. This study demonstrates a general approach that can be used to
      determine the influence of landscape variables on population genetic structure.

PMID- 15969735
TI  - Half-sib family structure of Fagus crenata saplings in an old-growth beech-dwarf
      bamboo forest.
AB  - Half-sib family structure of Fagus crenata saplings was examined in an old-growth
      beech-dwarf bamboo (Sasa spp.) forest using microsatellite genotypes in parentage
      analysis to identify the half-sib families in two 50 x 50 m plots: one with 36
      adults, 641 saplings and no Sasa cover, the other with 21 adults, 61 saplings and
      Sasa cover. For large proportions of the saplings (44.6% and 75.4%, respectively)
      both of their parents were found within the same plot, indicating that
      pollination events frequently involved short-range pollen dispersal, probably
      because of the high density of adults in the study population. Although almost
      all of the adults had half-sib families, the number of offspring in the families
      was highly variable. In the plot with no Sasa cover, the variation in the number
      of offspring was significantly explained by the size of parents, i.e. the
      reproductive success is higher for large adults than for small adults. The half
      sibs were aggregately distributed around their parents and the distribution
      overlapped among different half-sib families, which may be due to the limited
      seed dispersal and overlapping seed shadows of this species. As expected, there
      was weak genetic structure in the plot. By contrast, in the plot with Sasa cover,
      the half-sibs were distributed sparsely with a low density, and the degree of
      genetic structure was very weak. The difference in the half-sib family structure
      and genetic structure among saplings presumably reflects the difference in
      density that should be affected by regeneration dynamics associated with
      environmental conditions.

PMID- 15969736
TI  - Genetic structure and environmental heterogeneity in the European hake
      (Merluccius merluccius).
AB  - This study aimed at assessing the genetic structure and the state of the stocks
      of the European hake (Merluccius merluccius). To this end, 15 samples were taken
      from the whole range of the species and analysed using allozymes. Since 11
      samples were taken from the poorly studied Mediterranean Sea, the results
      obtained provided a complete picture of the hake's genetic structure and an
      initial insight into its relationships with environmental features. Atlantic and
      Mediterranean hake populations are separated by the Almeria-Oran front. This area
      has been proved to be the boundary between Atlantic and Mediterranean stocks of
      many marine organisms, but some doubt exists concerning the efficaciousness of
      the local gyres as barriers to the gene flow. Our data have evidenced a
      latitudinal cline at loci Gapdh and Gpi-2 within the Mediterranean Sea, with a
      further steep change across the Almeria-Oran front. The genetic pattern showed a
      strong correlation with the values of the salinity both at the surface and at 
      320 m and of the salinity + temperature at the surface, suggesting a role for
      these parameters in maintaining the genetic differentiation among the two
      population groups through selective processes. Finally, the levels of genetic
      variability were found to be slightly lower in the depleted Atlantic stock than
      in the Mediterranean one.

PMID- 15969737
TI  - Testing marker-based estimates of heritability in the wild.
AB  - Marker-based estimates of heritability are an attractive alternative to pedigree
      based methods for estimating quantitative genetic parameters in field studies
      where it is difficult or impossible to determine relationships and pedigrees.
      Here I test the ability of the marker-based method to estimate heritability of a
      suite of traits in a wild population of bighorn sheep (Ovis canadensis) using
      marker data from 32 microsatellite loci. I compared marker-based estimates with
      estimates obtained using a pedigree and the animal model. Marker-based estimates
      of heritability were imprecise and downwardly biased. The high degree of
      uncertainty in marker-based estimates suggests that the method may be sufficient
      to detect the presence of genetic variance for highly heritable traits, but not
      sufficiently reliable to estimate genetic parameters.

PMID- 15969738
TI  - Comparison of quantitative and molecular variation in agroforestry populations of
      the shea tree (Vitellaria paradoxa C.F. Gaertn) in Mali.
AB  - In this study we investigated the within- and between-population genetic
      variation using microsatellite markers and quantitative traits of the shea tree,
      Vitellaria paradoxa, an important agroforestry tree species of the Sudano
      Sahelian region in Africa. Eleven populations were sampled across Mali and in
      northern Cote d'Ivoire. Leaf size and form and growth traits were measured in a
      progeny test at the nursery stage. Eight microsatellites were used to assess
      neutral genetic variation. Low levels of heterozygosity were recorded (1.6-3.0
      alleles/locus; H(E) = 0.25-0.42) and the fixation index (F(IS) = -0.227-0.186)
      was not significantly different from zero suggesting that Hardy-Weinberg
      equilibrium is encountered in all populations sampled. Quantitative traits
      exhibited a strong genetic variation between populations and between families
      within populations. The degree of population differentiation of the quantitative
      traits (Q(ST) = 0.055-0.283, Q(STmean) = 0.189) strongly exceeds that in eight
      microsatellite loci (F(ST) = -0.011-0.142, F(STmean) = 0.047). Global and
      pairwise F(ST) values were very low and not significantly different from zero
      suggesting agroforestry practices are amplifying gene flow (Nm = 5.07). The
      population means for quantitative traits and the rainfall variable were not
      correlated, showing variation was not linked with this climatic cline. It is
      suggested that this marked differentiation for quantitative traits, independent
      of environmental clines and despite a high gene flow, is a result of local
      adaptation and human selection of shea trees. This process has induced high
      linkage disequilibrium between underlying loci of polygenic characters.

PMID- 15969739
TI  - Detecting the number of clusters of individuals using the software STRUCTURE: a
      simulation study.
AB  - The identification of genetically homogeneous groups of individuals is a long
      standing issue in population genetics. A recent Bayesian algorithm implemented in
      the software STRUCTURE allows the identification of such groups. However, the
      ability of this algorithm to detect the true number of clusters (K) in a sample
      of individuals when patterns of dispersal among populations are not homogeneous
      has not been tested. The goal of this study is to carry out such tests, using
      various dispersal scenarios from data generated with an individual-based model.
      We found that in most cases the estimated 'log probability of data' does not
      provide a correct estimation of the number of clusters, K. However, using an ad
      hoc statistic DeltaK based on the rate of change in the log probability of data
      between successive K values, we found that STRUCTURE accurately detects the
      uppermost hierarchical level of structure for the scenarios we tested. As might
      be expected, the results are sensitive to the type of genetic marker used (AFLP
      vs. microsatellite), the number of loci scored, the number of populations
      sampled, and the number of individuals typed in each sample.

PMID- 15969741
TI  - Multiple calcium channels and kinases mediate alpha7 nicotinic receptor
      neuroprotection in PC12 cells.
AB  - alpha7 Nicotinic receptors are calcium permeant and provide neuroprotection
      against many insults. We investigated the roles of intracellular calcium ions and
      downstream calcium channels in this protection. The alpha7 agonist GTS-21
      prevented pheochromocytoma cell death induced by nerve growth factor + serum
      deprivation over a 3-day interval. This effect was blocked by the intracellular
      calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid in a
      manner that did not appear to involve changes in receptor density. 1,2-Bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid blocked GTS-21-induced protein
      kinase C activation, a necessary process for protection. The insositol
      triphosphate calcium-channel blocker xestospongin C and the phospholipases C
      inhibitor U-73122 blocked protection, ryanodine partially attenuated protection,
      but the L-type channel antagonist nifedipine had no effect. ERK1/2 but not JNK
      and p38 were activated by GTS-21, and the ERK phosphorylation inhibitors PD98059
      and U0126 blocked protection.

PMID- 15969742
TI  - Astrocyte- and hepatocyte-specific expression of genes from the distal serpin
      subcluster at 14q32.1 associates with tissue-specific chromatin structures.
AB  - The distal serpin subcluster contains genes encoding alpha1-antichymotrypsin
      (ACT), protein C inhibitor (PCI), kallistatin (KAL) and the KAL-like protein,
      which are expressed in hepatocytes, but only the act gene is expressed in
      astrocytes. We show here that the tissue-specific expression of these genes
      associates with astrocyte- and hepatocyte-specific chromatin structures. In
      hepatocytes, we identified 12 Dnase I-hypersensitive sites (DHSs) that were
      distributed throughout the entire subcluster, with the promoters of expressed
      genes accessible to restriction enzyme digestion. In astrocytes, only six DHSs
      were located exclusively in the 5' flanking region of the act gene, with its
      promoter also accessible to restriction enzyme digestion. The acetylation of
      histone H3 and H4 was found throughout the subcluster in both cell types but this
      acetylation did not correlate with the expression pattern of these serpin genes.
      Analysis of histone modifications at the promoters of the act and pci genes
      revealed that methylation of histone H3 on lysine 4 correlated with their
      expression pattern in both cell types. In addition, inhibition of
      methyltransferase activity resulted in suppression of ACT and PCI mRNA
      expression. We propose that lysine 4 methylation of histone H3 correlates with
      the tissue-specific expression pattern of these serpin genes.

PMID- 15969743
TI  - Nuclear factor-kappaB activation by reactive oxygen species mediates voltage
      gated K+ current enhancement by neurotoxic beta-amyloid peptides in nerve growth
      factor-differentiated PC-12 cells and hippocampal neurones.
AB  - Increased activity of plasma membrane K+ channels, leading to decreased
      cytoplasmic K+ concentrations, occurs during neuronal cell death. In the present
      study, we showed that the neurotoxic beta-amyloid peptide Abeta(25-35) caused a
      dose-dependent (0.1-10 microm) and time-dependent (> 12 h) enhancement of both
      inactivating and non-inactivating components of voltage-dependent K+ (VGK)
      currents in nerve growth factor-differentiated rat phaeochromocytoma (PC-12)
      cells and primary rat hippocampal neurones. Similar effects were exerted by
      Abeta(1-42), but not by the non-neurotoxic Abeta(35-25) peptide. Abeta(25-35) and
      Abeta(1-42) caused an early (15-20 min) increase in intracellular Ca(2+)
      concentration. This led to an increased production of reactive oxygen species
      (ROS), which peaked at 3 h and lasted for 24 h; ROS production seemed to trigger
      the VGK current increase as vitamin E (50 microm) blocked both the Abeta(25-35)-
      and Abeta(1-42)-induced ROS increase and VGK current enhancement. Inhibition of
      protein synthesis (cycloheximide, 1 microg/mL) and transcription (actinomycin D,
      50 ng/mL) blocked Abeta(25-35)-induced VGK current enhancement, suggesting that
      this potentiation is mediated by transcriptional activation induced by ROS.
      Interestingly, the specific nuclear factor-kappaB inhibitor SN-50 (5 microm), but
      not its inactive analogue SN-50M (5 microm), fully counteracted Abeta(1-42)- or
      Abeta(25-35)-induced enhancement of VGK currents, providing evidence for a role
      of this family of transcription factors in regulating neuronal K+ channel
      function during exposure to Abeta.

PMID- 15969744
TI  - Clinical presentation of abdominal tuberculosis in HIV seronegative adults.
AB  - BACKGROUND: The accurate diagnosis of abdominal tuberculosis usually takes a long
      time and requires a high index of suspicion in clinic practice. Eighty-eight
      immune-competent patients with abdominal tuberculosis were grouped according to
      symptoms at presentation and followed prospectively in order to investigate the
      effect of symptomatic presentation on clinical diagnosis and prognosis. METHODS:
      Based upon the clinical presentation, the patients were divided into groups such
      as non-specific abdominal pain & less prominent in bowel habit, ascites,
      alteration in bowel habit, acute abdomen and others. Demographic, clinical and
      laboratory features, coexistence of pulmonary tuberculosis, diagnostic
      procedures, definitive diagnostic tests, need for surgical therapy, and response
      to treatment were assessed in each group. RESULTS: According to clinical
      presentation, five groups were constituted as non-specific abdominal pain (n =
      24), ascites (n = 24), bowel habit alteration (n = 22), acute abdomen (n = 9) and
      others (n = 9). Patients presenting with acute abdomen had significantly higher
      white blood cell counts (p = 0.002) and abnormalities in abdominal plain
      radiographs (p = 0.014). Patients presenting with alteration in bowel habit were
      younger (p = 0.048). The frequency of colonoscopic abnormalities (7.5%), and need
      for therapeutic surgery (12.5%) were lower in patients with ascites, (p = 0.04)
      and (p = 0.001), respectively. There was no difference in gender, disease
      duration, diagnostic modalities, response to treatment, period to initial
      response, and mortality between groups (p > 0.05). Gastrointestinal tract alone
      was the most frequently involved part (38.5%), and this was associated with acid
      fast bacteria in the sputum (p = 0.003). CONCLUSION: Gastrointestinal tract
      involvement is frequent in patients with active pulmonary tuberculosis. Although
      different clinical presentations of patients with abdominal tuberculosis
      determine diagnostic work up and need for therapeutic surgery, evidence based
      diagnosis and consequences of the disease does not change.

PMID- 15969745
TI  - Difference in trafficking of brain-derived neurotrophic factor between axons and
      dendrites of cortical neurons, revealed by live-cell imaging.
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF), which is sorted into a
      regulated secretory pathway of neurons, is supposed to act retrogradely through
      dendrites on presynaptic neurons or anterogradely through axons on postsynaptic
      neurons. Depending on which is the case, the pattern and direction of trafficking
      of BDNF in dendrites and axons are expected to be different. To address this
      issue, we analyzed movements of green fluorescent protein (GFP)-tagged BDNF in
      axons and dendrites of living cortical neurons by time-lapse imaging. In part of
      the experiments, the expression of BDNF tagged with cyan fluorescent protein
      (CFP) was compared with that of nerve growth factor (NGF) tagged with yellow
      fluorescent protein (YFP), to see whether fluorescent protein-tagged BDNF is
      expressed in a manner specific to this neurotrophin. RESULTS: We found that BDNF
      tagged with GFP or CFP was expressed in a punctated manner in dendrites and axons
      in about two-thirds of neurons into which plasmid cDNAs had been injected, while
      NGF tagged with GFP or YFP was diffusely expressed even in dendrites in about 70%
      of the plasmid-injected neurons. In neurons in which BDNF-GFP was expressed as
      vesicular puncta in axons, 59 and 23% of the puncta were moving rapidly in the
      anterograde and retrograde directions, respectively. On the other hand, 64% of
      BDNF-GFP puncta in dendrites did not move at all or fluttered back and forth
      within a short distance. The rest of the puncta in dendrites were moving
      relatively smoothly in either direction, but their mean velocity of transport,
      0.47 +/- 0.23 (SD) microm/s, was slower than that of the moving puncta in axons
      (0.73 +/- 0.26 microm/s). CONCLUSION: The present results show that the pattern
      and velocity of the trafficking of fluorescence protein-tagged BDNF are different
      between axons and dendrites, and suggest that the anterograde transport in axons
      may be the dominant stream of BDNF to release sites.

PMID- 15969746
TI  - Morbidity and mortality after esophagectomy for esophageal carcinoma: a risk
      analysis.
AB  - BACKGROUND: The study was aimed to identify pre- and intraoperative risk factors
      that potentially influence morbidity and mortality after esophagectomy for
      esophageal carcinoma with particular emphasis on the predominant tumor types.
      PATIENTS AND METHODS: Between September 1985 and March 2004, 424 patients
      underwent esophagectomy for esophageal carcinoma. Of these, 186 (43.9%) patients
      had a transhiatal, and 231 (54.5%) patients underwent a transthoracic procedure
      with two-field lymphadenectomy. Pre-, intraoperative risk factors and tumor
      characteristics were included in the risk analysis to assess their influence on
      postoperative morbidity and mortality. RESULTS: Multivariate analysis (logistic
      regression model) identified the surgical procedure as the most important risk
      factor for postoperative morbidity and mortality with the transthoracic technique
      associated with a significant higher risk. The comparison of the risk profile
      between the different histological tumor types, a significantly higher
      nutritional risk, poorer preoperative lung function and a higher prevalence of
      hepatopathy was observed in patients with squamous cell carcinoma (n = 229)
      compared to adenocarcinoma (n = 150) (p < 0.05). Although there was no
      significant difference in surgical complications between the two groups, the rate
      of general complications, length of postoperative intensive care unit-stay and
      mortality rate was significantly higher in patients with squamous cell carcinoma
      (p < 0.05). CONCLUSION: The present risk analysis shows that the selection and
      the type of the surgical procedure are crucial factors for both the incidence of
      postoperative complications and the mortality rate. The higher risk of the
      transthoracic procedure is justified with a view to a better long term prognosis.

PMID- 15969747
TI  - Diagnostic and prognostic utility of an inexpensive rapid on site malaria
      diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low
      and no transmission in central India.
AB  - BACKGROUND: Malaria presents a diagnostic challenge in most tropical countries.
      Rapid detection of the malaria parasite and early treatment of infection still
      remain the most important goals of disease management. Therefore, performance
      characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat,
      India) was determined among ethnic tribal population in four districts of
      different transmission potential in central India to assess whether this rapid
      diagnostic test (RDT) could be widely applied as a diagnostic tool to control
      malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor
      treatment outcome. METHODS: A finger prick blood sample was collected from each
      clinically suspected case of malaria to prepare blood smear and for testing with
      the RDT after taking informed consent. The blood smears were read by an
      experienced technician blinded to the RDT results and clinical status of the
      subjects. The figures for specificity, sensitivity, accuracy and predictive
      values were calculated using microscopy as gold standard. RESULTS: The prevalence
      of malaria infection estimated by RDT in parallel with microscopy provide
      evidence of the type of high, low or no transmission in the study area. Analysis
      revealed (pooled data of all four epidemiological settings) that overall
      sensitivity, specificity and accuracy of the RDT were >90% in areas of different
      endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic
      cases of suspected P. falciparum infection, the persistence of parasite antigen
      leading to false positives even after clearance of asexual parasitaemia has
      limited its utility as a prognostic tool. CONCLUSION: The study showed that the
      ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an
      appropriate test for the use in the field by paramedical staff when laboratory
      facilities are not available and thus likely to contribute greatly to an
      effective control of malaria in resource poor countries.

PMID- 15969749
TI  - Real time spatial cluster detection using interpoint distances among precise
      patient locations.
AB  - BACKGROUND: Public health departments in the United States are beginning to gain
      timely access to health data, often as soon as one day after a visit to a health
      care facility. Consequently, new approaches to outbreak surveillance are being
      developed. When cases cluster geographically, an analysis of their spatial
      distribution can facilitate outbreak detection. Our method focuses on detecting
      perturbations in the distribution of pair-wise distances among all patients in a
      geographical region. Barring outbreaks, this distribution can be quite stable
      over time. We sought to exemplify the method by measuring its cluster detection
      performance, and to determine factors affecting sensitivity to spatial clustering
      among patients presenting to hospital emergency departments with respiratory
      syndromes. METHODS: The approach was to (1) define a baseline spatial
      distribution of home addresses for a population of patients visiting an emergency
      department with respiratory syndromes using historical data; (2) develop a
      controlled feature set simulation by inserting simulated outbreak data with
      varied parameters into authentic background noise, thereby creating semisynthetic
      data; (3) compare the observed with the expected spatial distribution; (4)
      establish the relative value of different alarm strategies so as to maximize
      sensitivity for the detection of clustering; and (5) measure factors which have
      an impact on sensitivity. RESULTS: Overall sensitivity to detect spatial
      clustering was 62%. This contrasts with an overall alarm rate of less than 5% for
      the same number of extra visits when the extra visits were not characterized by
      geographic clustering. Clusters that produced the least number of alarms were
      those that were small in size (10 extra visits in a week, where visits per week
      ranged from 120 to 472), diffusely distributed over an area with a 3 km radius,
      and located close to the hospital (5 km) in a region most densely populated with
      patients to this hospital. Near perfect alarm rates were found for clusters that
      varied on the opposite extremes of these parameters (40 extra visits, within a
      250 meter radius, 50 km from the hospital). CONCLUSION: Measuring perturbations
      in the interpoint distance distribution is a sensitive method for detecting
      spatial clustering. When cases are clustered geographically, there is clearly
      power to detect clustering when the spatial distribution is represented by the M
      statistic, even when clusters are small in size. By varying independent
      parameters of simulated outbreaks, we have demonstrated empirically the limits of
      detection of different types of outbreaks.

PMID- 15969748
TI  - Ovarian cancer, the coagulation pathway, and inflammation.
AB  - Epithelial ovarian cancer (EOC) represents the most frequent cause of death in
      the United States from a cancer involving the female genital tract. Contributing
      to the overall poor outcome in EOC patients, are the metastases to the peritoneum
      and stroma that are common in this cancer. In one study, cDNA microarray analysis
      was performed on fresh tissue to profile gene expression in patients with EOC.
      This study showed a number of genes with significantly altered expression in the
      pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes
      included those encoding coagulation factors and regulatory proteins in the
      coagulation cascade and genes encoding proteins associated with inflammatory
      responses. In addition to promoting the formation of blood clots, coagulation
      factors exhibit many other biologic functions as well as tumorigenic functions,
      the later including tumor cell proliferation, angiogenesis, invasion, and
      metastasis. Coagulation pathway proteins involved in tumorigenesis consist of
      factor II (thrombin), thrombin receptor (protease-activated receptors), factor
      III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin
      and factor XIII. In a recent study we conducted, we found that factor XII, factor
      XI, and several coagulation regulatory proteins, including heparin cofactor-II
      and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum
      of EOC. In this review, we summarize evidence in support of a role for these
      factors in promoting tumor cell progression and the formation of ascites. We also
      discuss the different roles of coagulation factor pathways in the tumor and
      peritumoral microenvironments as they relate to angiogenesis, proliferation,
      invasion, and metastasis. Since inflammatory responses are another characteristic
      of the peritoneum in EOC, we also discuss the linkage between the coagulation
      cascade and the cytokines/chemokines involved in inflammation. Interleukin-8,
      which is considered an important chemokine associated with tumor progression,
      appears to be a linkage point for coagulation and inflammation in malignancy.
      Lastly, we review findings regarding the inflammatory process yielded by certain
      clinical trials of agents that target members of the coagulation cascade in the
      treatment of cancer. Current data suggest that disrupting certain elements of the
      coagulation and inflammation processes in the tumor microenvironment could be a
      new biologic approach to cancer therapeutics.

PMID- 15969750
TI  - Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and
      caveolin-1.
AB  - BACKGROUND: In the current study we investigated the role of caveolin-1 (cav-1)
      in pancreatic adenocarcinoma (PC) cell migration and invasion; initial steps in
      metastasis. Cav-1 is the major structural protein in caveolae; small Omega-shaped
      invaginations within the plasma membrane. Caveolae are involved in signal
      transduction, wherein cav-1 acts as a scaffolding protein to organize multiple
      molecular complexes regulating a variety of cellular events. Recent evidence
      suggests a role for cav-1 in promoting cancer cell migration, invasion and
      metastasis; however, the molecular mechanisms have not been described. The small
      monomeric GTPases are among several molecules which associate with cav-1.
      Classically, the Rho GTPases control actin cytoskeletal reorganization during
      cell migration and invasion. RhoC GTPase is overexpressed in aggressive cancers
      that metastasize and is the predominant GTPase in PC. Like several GTPases, RhoC
      contains a putative cav-1 binding motif. RESULTS: Analysis of 10 PC cell lines
      revealed high levels of cav-1 expression in lines derived from primary tumors and
      low expression in those derived from metastases. Comparison of the BxPC-3
      (derived from a primary tumor) and HPAF-II (derived from a metastasis)
      demonstrates a reciprocal relationship between cav-1 expression and p42/p44 Erk
      activation with PC cell migration, invasion, RhoC GTPase and p38 MAPK activation.
      Furthermore, inhibition of RhoC or p38 activity in HPAF-II cells leads to partial
      restoration of cav-1 expression. CONCLUSION: Cav-1 expression inhibits RhoC
      GTPase activation and subsequent activation of the p38 MAPK pathway in primary PC
      cells thus restricting migration and invasion. In contrast, loss of cav-1
      expression leads to RhoC-mediated migration and invasion in metastatic PC cells.

PMID- 15969751
TI  - Analysis of xylem sap proteins from Brassica napus.
AB  - BACKGROUND: Substance transport in higher land plants is mediated by vascular
      bundles, consisting of phloem and xylem strands that interconnect all plant
      organs. While the phloem mainly allocates photoassimilates, the role of the xylem
      is the transport of water and inorganic nutrients from roots to all aerial plant
      parts. Only recently it was noticed that in addition to mineral salts, xylem sap
      contains organic nutrients and even proteins. Although these proteins might have
      important impact on the performance of above-ground organs, only a few of them
      have been identified so far and their physiological functions are still unclear.
      RESULTS: We used root-pressure xylem exudate, collected from cut Brassica napus
      stems, to extract total proteins. These protein preparations were then separated
      by high-resolution two-dimensional gel electrophoresis (2-DE). After individual
      tryptic digests of the most abundant coomassie-stained protein spots, partial
      peptide sequence information was deduced from tandem mass spectrometric (MS/MS)
      fragmentation spectra and subsequently used for protein identifications by
      database searches. This approach resulted in the identification of 69 proteins.
      These identifications include different proteins potentially involved in defence
      related reactions and cell wall metabolism. CONCLUSION: This study provides a
      comprehensive overview of the most abundant proteins present in xylem sap of
      Brassica napus. A number of 69 proteins could be identified from which many
      previously were not known to be localized to this compartment in any other plant
      species. Since Brassica napus, a close relative of the fully sequenced model
      plant Arabidopsis thaliana, was used as the experimental system, our results
      provide a large number of candidate proteins for directed molecular and
      biochemical analyses of the physiological functions of the xylem under different
      environmental and developmental conditions. This approach will allow exploiting
      many of the already established functional genomic resources, like i.e. the large
      mutant collections, that are available for Arabidopsis.

PMID- 15969752
TI  - Amplitude-dependency of response of SI cortex to flutter stimulation.
AB  - BACKGROUND: It is established that increasing the amplitude of a flutter stimulus
      increases its perceived intensity. Although many studies have examined this
      phenomenon with regard to the responding afferent population, the way in which
      the intensity of a stimulus is coded in primary somatosensory cortex (SI) remains
      unclear. RESULTS: Optical intrinsic signal (OIS) imaging was used to study the
      evoked responses in SI of anesthetized squirrel monkeys by 25 Hz sinusoidal
      vertical skin displacement stimulation. Stimuli were 10 sec duration with a 50
      sec inter-stimulus interval. Stimulus amplitude ranged from 50 to 400 microns and
      different amplitudes were interleaved. Control levels of activity were measured
      in the absence of stimulation, and used to compare with activation levels evoked
      by the different stimulus amplitudes. Stimulation of a discrete skin site on the
      forelimb evoked a prominent increase in absorbance within the forelimb
      representational region in cytoarchitectonic areas 3b and 1 of the contralateral
      hemisphere. An increase in stimulus amplitude led to a proportional increase in
      the magnitude of the absorbance increase in this region of areas 3b and 1 while
      surrounding cortex underwent a decrease in absorbance. Correlation maps revealed
      that as stimulus amplitude is increased, the spatial extent of the activated
      region in SI remains relatively constant, and the activity within this region
      increases progressively. Additionally, as stimulus amplitude is increased to
      suprathreshold levels, activity in the surround of the activated SI territory
      decreases, suggesting an increase in inhibition of neuronal activity within these
      regions. CONCLUSION: Increasing the amplitude of a flutter stimulus leads to a
      proportional increase in absorbance within the forelimb representational region
      of SI. This most likely reflects an increase in the firing rate of neurons in
      this region of SI. The relatively constant spatial extent of this stimulus-evoked
      increase in absorbance suggests that an increase in the amplitude of a 25 Hz skin
      stimulus does not evoke a larger area of SI neuronal activation due to an
      amplitude-dependent lateral inhibitory effect that spatially funnels the
      responding SI neuronal population.

PMID- 15969753
TI  - E-Cadherin and beta-Catenin expression in early stage cervical carcinoma: a
      tissue microarray study of 147 cases.
AB  - BACKGROUND: The disruption of intercellular adhesions is an important component
      of the acquisition of invasive properties in epithelial malignancies. Alterations
      in the cell-cell adhesion complex, E-Cadherin/beta-Catenin, have been implicated
      in the oncogenesis of carcinomas arising from various anatomic sites and have
      been correlated with adverse clinico-pathologic parameters. In this study, the
      authors investigated the immunohistochemical expression of E-Cadherin and beta
      Catenin in a cohort of early stage cervical cancers to determine its prognostic
      significance and to investigate differences between the three major histological
      subtypes. PATIENTS AND METHODS: A tissue microarray of 147 cases of FIGO stage 1A
      and 1B cervical carcinomas [96 squamous cell carcinomas (SCC), 35 adenocarcinomas
      (AC), 12 adenosquamous carcinomas (ASQ), 4 miscellaneous types] was constructed
      from our archived surgical pathology files and stained with monoclonal antibodies
      to E-Cadherin and beta-Catenin. Cases were scored by multiplying the intensity of
      staining (1 to 3 scale) by the percentage of cells stained (0-100%) for a
      potential maximum score of 300. For both markers, "preserved" expression was
      defined as bright membranous staining with a score of 200 or above. "Impaired"
      expression included any of the following: negative staining, a score less than
      200, or exclusively cytoplasmic or nuclear delocalization. RESULTS: Impaired
      expression of beta-Catenin was found in 85.7%, 66.7%, & 58.3% of AC, SCC & ASQ
      respectively. Impaired expression of E-Cadherin was found in 94.3%, 86.5% & 100%
      of cases of AC, SCC, & ASQ respectively. The differences between the histologic
      subtypes were not significant. For the whole cohort, a comparison of cases
      showing impaired versus preserved of E-Cadherin and beta-Catenin expression
      showed no significant differences with respect to recurrence free survival,
      overall survival, patient age, histologic grade, and frequency of lymphovascular
      invasion or lymph node involvement. There was no correlation between the status
      of both markers for all three histological subtypes (overall spearman correlation
      co-efficient r = 0.12, p = 0.14) CONCLUSION: Impairment of E-Cadherin and beta
      Catenin expression is very frequent in early stage cervical cancers, and
      alterations in the E-Cadherin/beta-Catenin cell adhesion complex are therefore
      likely involved in the pathogenesis of cervical carcinomas even at their earliest
      stages. None of the three major histological subtypes of cervical carcinoma (SCC,
      ADCA, ADSQ) is significantly more likely than the others to show impairment in E
      Cadherin and beta-Catenin expression. Overall, the expression of both markers
      does not significantly correlate with clinico-pathological parameters of
      prognostic significance.

PMID- 15969754
TI  - Immediate transfection of patient-derived leukemia: a novel source for generating
      cell-based vaccines.
AB  - BACKGROUND: The production of cell-based cancer vaccines by gene vectors encoding
      proteins that stimulate the immune system has advanced rapidly in model systems.
      We sought to develop non-viral transfection methods that could transform patient
      tumor cells into cancer vaccines, paving the way for rapid production of
      autologous cell-based vaccines. METHODS: As the extended culture and expansion of
      most patient tumor cells is not possible, we sought to first evaluate a new
      technology that combines electroporation and chemical transfection in order to
      determine if plasmid-based gene vectors could be instantaneously delivered to the
      nucleus, and to determine if gene expression was possible in a cell-cycle
      independent manner. We tested cultured cell lines, a primary murine tumor, and
      primary human leukemia cells from diagnostic work-up for transgene expression,
      using both RFP and CD137L expression vectors. RESULTS: Combined electroporation
      transfection directly delivered plasmid DNA to the nucleus of transfected cells,
      as demonstrated by confocal microscopy and real-time PCR analysis of isolated
      nuclei. Expression of protein from plasmid vectors could be detected as early as
      two hours post transfection. However, the kinetics of gene expression from
      plasmid-based vectors in tumor cell lines indicated that optimal gene expression
      was still dependent on cell division. We then tested to see if pediatric acute
      lymphocytic leukemia (ALL) would also display the rapid gene expression kinetics
      of tumor cells lines, determining gene expression 24 hours after transfection.
      Six of 12 specimens showed greater than 17% transgene expression, and all samples
      showed at least some transgene expression. CONCLUSION: Given that transgene
      expression could be detected in a majority of primary tumor samples analyzed
      within hours, direct electroporation-based transfection of primary leukemia holds
      the potential to generate patient-specific cancer vaccines. Plasmid-based gene
      therapy represents a simple means to generate cell-based cancer vaccines and does
      not require the extensive infrastructure of a virus-based vector system.

PMID- 15969755
TI  - Discovery of the photosynthetic relatives of the "Maltese mushroom" Cynomorium.
AB  - BACKGROUND: Although recent molecular phylogenetic studies have identified the
      photosynthetic relatives of several enigmatic holoparasitic angiosperms,
      uncertainty remains for the last parasitic plant order, Balanophorales, often
      considered to include two families, Balanophoraceae and Cynomoriaceae. The
      nonphotosynthetic (holoparasitic) flowering plant Cynomorium coccineum has long
      been known to the Muslim world as "tarthuth" and to Europeans as the "Maltese
      mushroom"; C. songaricum is known in Chinese medicine as "suo yang." Interest in
      these plants is increasing and they are being extensively collected from wild
      populations for use in herbal medicines. RESULTS: Here we report molecular
      phylogenetic analyses of nuclear ribosomal DNA and mitochondrial matR sequence
      data that strongly support the independent origin of Balanophoraceae and
      Cynomoriaceae. Analyses of single gene and combined gene data sets place
      Cynomorium in Saxifragales, possibly near Crassulaceae (stonecrop family).
      Balanophoraceae appear related to Santalales (sandalwood order), a position
      previously suggested from morphological characters that are often assumed to be
      convergent. CONCLUSION: Our work shows that Cynomorium and Balanophoraceae are
      not closely related as indicated in all past and present classifications. Thus,
      morphological features, such as inflorescences bearing numerous highly reduced
      flowers, are convergent and were attained independently by these two holoparasite
      lineages. Given the widespread harvest of wild Cynomorium species for herbal
      medicines, we here raise conservation concerns and suggest that further molecular
      phylogenetic work is needed to identify its photosynthetic relatives. These
      relatives, which will be easier to cultivate, should then be examined for
      phytochemical activity purported to be present in the more sensitive Cynomorium.

PMID- 15969756
TI  - A link between high serum levels of human chorionic gonadotrophin and chorionic
      expression of its mature functional receptor (LHCGR) in Down's syndrome
      pregnancies.
AB  - Human chorionic gonadotrophin (hCG) is released from placental trophoblasts and
      is involved in establishing pregnancy by maintaining progesterone secretion from
      the corpus luteum. Serum hCG is detected in the maternal circulation within the
      first 2-3 wks of gestation and peaks at the end of the first trimester before
      declining. In Down's syndrome (DS) pregnancies, serum hCG remains significantly
      high compared to gestation age-matched uncompromised pregnancies. It has been
      proposed that increased serum hCG levels could be due to transcriptional hyper
      activation of the CGB (hCG beta) gene, or an increased half life of glycosylated
      hCG hormone, or both. Another possibility is that serum hCG levels remain high
      due to reduced availability of the hormone's cognate receptor, LHCGR, leading to
      lack of hormone utilization. We have tested this hypothesis by quantifying the
      expression of the hCG beta (CGB) RNA, LHCGR RNA and LHCGR proteins in chorionic
      villous samples. We demonstrate that chorionic expression of hCG beta (CGB) mRNA
      directly correlates with high serum hCG levels. The steady-state synthesis of
      LHCGR mRNA (exons 1-5) in DS pregnancies was significantly higher than that of
      controls, but the expression of full-length LHCGR mRNA (exons 1-11) in DS was
      comparable to that of uncompromised pregnancies. However, the synthesis of high
      molecular weight mature LHCGR proteins was significantly reduced in DS compared
      to uncompromised pregnancies, suggesting a lack of utilization of circulating hCG
      in DS pregnancies.

PMID- 15969757
TI  - The presence of the proteolysis-inducing factor in urine does not predict the
      malignancy of a pancreatic tumour.
AB  - BACKGROUND: The proteolysis-inducing factor (PIF) was identified as a tumour
      product in various gastrointestinal cancers. A previous study in pancreatic
      cancer patients suggested PIF expression as a tumour marker, which is not related
      to tumour size. We hypothesized that PIF could be a useful marker to exclude
      benign pancreatic tumors, as chronic pancreatitis with a pancreatic mass.
      METHODS: Urine of patients with a pancreatic mass of uncertain malignancy was
      investigated for PIF expression by Western blot. Sufficient urine protein for
      analysis was available in 59 patients. The diagnosis was established by histology
      in 54 patients and by follow up in five patients with chronic pancreatitis. In
      addition, serum CA19-9 was measured. RESULTS: The sensitivity (specifity) for the
      detection of a malignant pancreatic tumour was 90% (75%) and 54% (71%) for CA19-9
      and PIF, respectively. The sensitivity (specifity) for the distinction of
      pancreatic cancer from chronic pancreatitis was 89% (80%) and 57% (63%) for CA19
      9 and PIF, respectively. CONCLUSION: Evaluation of PIF in urine is of no
      diagnostic value in patients with a pancreatic mass of unknown malignancy.

PMID- 15969758
TI  - Influenza associated excess mortality in Germany, 1985-2001.
AB  - Influenza-associated excess mortality is widely used to assess the severity of
      influenza epidemics. In Germany, however, it is not yet established as a routine
      component of influenza surveillance. We therefore applied a simple method based
      on the annual distribution of monthly relative mortality (relative mortality
      distribution method, RMDM) to a time-series of German monthly all-cause mortality
      data from 1985-2001 to estimate influenza-associated excess mortality. Results
      were compared to those obtained by cyclical regression. Both methods
      distinguished stronger from milder influenza seasons, but RMDM gave the better
      fit (R2 = 0.80). For the years after reunification, i.e. 1990/91 through 2000/01,
      RMDM yielded an average of 6900 (conservative estimate) to 13,600 influenza
      associated excess deaths per season (crude estimate). The most severe epidemics
      occurred during subtype A/H3N2 seasons. While German all-cause mortality declined
      over the study period, the number of excess deaths displayed an upward trend,
      coinciding with an increase of the proportion of the elderly population.

PMID- 15969759
TI  - Calcium-fortified beverage supplementation on body composition in postmenopausal
      women.
AB  - BACKGROUND: We investigated the effects of a calcium-fortified beverage
      supplemented over 12 months on body composition in postmenopausal women (n = 37,
      age = 48-75 y). METHODS: Body composition (total-body percent fat, %FatTB;
      abdominal percent fat, %FatAB) was measured with dual energy x-ray
      absorptiometry. After baseline assessments, subjects were randomly assigned to a
      free-living control group (CTL) or the supplement group (1,125 mg Ca++/d, CAL).
      Dietary intake was assessed with 3-day diet records taken at baseline and 12
      months (POST). Physical activity was measured using the Yale Physical Activity
      Survey. RESULTS: At 12 months, the dietary calcium to protein ratio in the CAL
      group (32.3 +/- 15.6 mg/g) was greater than the CTL group (15.2 +/- 7.5 mg/g).
      There were no differences from baseline to POST between groups for changes in
      body weight (CAL = 0.1 +/- 3.0 kg; CTL = 0.0 +/- 2.9 kg), %FatTB (CAL = 0.0 +/-
      2.4%; CTL = 0.5 +/- 5.4%), %FatAB (CAL = -0.4 +/- 8.7%; CTL = 0.6 +/- 8.7%), or
      fat mass (CAL = 1.3 +/- 2.6 kg; CTL = 1.3 +/- 2.7 kg). CONCLUSION: These results
      indicate that increasing the calcium to protein ratio over two-fold by consuming
      a calcium-fortified beverage for 12 months did not decrease body weight, body
      fat, or abdominal fat composition in postmenopausal women.

PMID- 15969760
TI  - Bone mineral density measurement and osteoporosis treatment after a fragility
      fracture in older adults: regional variation and determinants of use in Quebec.
AB  - BACKGROUND: Osteoporosis (OP) is a skeletal disorder characterized by reduced
      bone strength and predisposition to increased risk of fracture, with consequent
      increased risk of morbidity and mortality. It is therefore an important public
      health problem. International and Canadian associations have issued clinical
      guidelines for the diagnosis and treatment of OP. In this study, we identified
      potential predictors of bone mineral density (BMD) testing and OP treatment,
      which include place of residence. METHODS: Our study was a retrospective
      population-based cohort study using data from the Quebec Health Insurance Board.
      The studied population consisted of all individuals 65 years and older for whom a
      physician claimed a consultation for a low velocity vertebral, hip, wrist, or
      humerus fracture in 1999 and 2000. Individuals were considered to have undergone
      BMD testing if there was a claim for such a procedure within two years following
      a fracture. They were considered to have received an OP treatment if there was at
      least one claim to Quebec's health insurance plan (RAMQ) for OP treatment within
      one year following a fracture. We performed descriptive analyses and logistic
      regressions by gender. Predictors included age, site of fracture, social status,
      comorbidity index, prior BMD testing, prior OP treatment, long-term
      glucocorticoid use, and physical distance to BMD device. RESULTS: The cohort, 77%
      of which was female, consisted of 25,852 individuals with fragility fractures.
      BMD testing and OP treatment rates were low and gender dependent (BMD: men 4.6%;
      women 13.1%; OP treatment: men 9.9%; women 29.7%). There was an obvious regional
      variation, particularly in BMD testing, ranging from 0 to 16%. Logistic
      regressions demonstrate that individuals living in long term care facilities
      received less BMD testing. Patients who had suffered from vertebral fractures, or
      who had received prior OP treatment or BMD testing, regardless of gender,
      subsequently received more BMD testing and OP treatments. Furthermore, increasing
      the distance between a patient's residence and BMD facility precluded likelihood
      of BMD testing. CONCLUSION: BMD testing rate was extremely low but not completely
      explained by reduced physical access; gender, age, social status, prior BMD
      testing and OP treatment were all important predictors for future BMD testing and
      OP treatment.

PMID- 15969762
TI  - Improved lung preservation relates to an increase in tubular myelin-associated
      surfactant protein A.
AB  - BACKGROUND: Declining levels of surfactant protein A (SP-A) after lung
      transplantation are suggested to indicate progression of ischemia/reperfusion
      (IR) injury. We hypothesized that the previously described preservation-dependent
      improvement of alveolar surfactant integrity after IR was associated with
      alterations in intraalveolar SP-A levels. METHODS: Using immuno electron
      microscopy and design-based stereology, amount and distribution of SP-A, and of
      intracellular surfactant phospholipids (lamellar bodies) as well as infiltration
      by polymorphonuclear leukocytes (PMNs) and alveolar macrophages were evaluated in
      rat lungs after IR and preservation with EuroCollins or Celsior. RESULTS: After
      IR, labelling of tubular myelin for intraalveolar SP-A was significantly
      increased. In lungs preserved with EuroCollins, the total amount of intracellular
      surfactant phospholipid was reduced, and infiltration by PMNs and alveolar
      macrophages was significantly increased. With Celsior no changes in infiltration
      or intracellular surfactant phospholipid amount occurred. Here, an increase in
      the number of lamellar bodies per cell was associated with a shift towards
      smaller lamellar bodies. This accounts for preservation-dependent changes in the
      balance between surfactant phospholipid secretion and synthesis as well as in
      inflammatory cell infiltration. CONCLUSION: We suggest that enhanced release of
      surfactant phospholipids and SP-A represents an early protective response that
      compensates in part for the inactivation of intraalveolar surfactant in the early
      phase of IR injury. This beneficial effect can be supported by adequate lung
      preservation, as e.g. with Celsior, maintaining surfactant integrity and reducing
      inflammation, either directly (via antioxidants) or indirectly (via improved
      surfactant integrity).

PMID- 15969763
TI  - Palm is expressed in both developing and adult mouse lens and retina.
AB  - BACKGROUND: Paralemmin (Palm) is a prenyl-palmitoyl anchored membrane protein
      that can drive membrane and process formation in neurons. Earlier studies have
      shown brain preferred Palm expression, although this protein is a major water
      insoluble protein in chicken lens fiber cells and the Palm gene may be regulated
      by Pax6. METHODS: The expression profile of Palm protein in the embryonic,
      newborn and adult mouse eye as well as dissociated retinal neurons was determined
      by confocal immunofluorescence. The relative mRNA levels of Palm, Palmdelphin
      (PalmD) and paralemmin2 (Palm2) in the lens and retina were determined by real
      time rt-PCR. RESULTS: In the lens, Palm is already expressed at 9.5 dpc in the
      lens placode, and this expression is maintained in the lens vesicle throughout
      the formation of the adult lens. Palm is largely absent from the optic vesicle
      but is detectable at 10.5 dpc in the optic cup. In the developing retina, Palm
      expression transiently upregulates during the formation of optic nerve as well as
      in the formation of both the inner and outer plexiform layers. In short term
      dissociated chick retinal cultures, Palm protein is easily detectable, but the
      levels appear to reduce sharply as the cultures age. Palm mRNA was found at much
      higher levels relative to Palm2 or PalmD in both the retina and lens. CONCLUSION:
      Palm is the major paralemmin family member expressed in the retina and lens and
      its expression in the retina transiently upregulates during active neurite
      outgrowth. The expression pattern of Palm in the eye is consistent with it being
      a Pax6 responsive gene. Since Palm is known to be able to drive membrane
      formation in brain neurons, it is possible that this molecule is crucial for the
      increase in membrane formation during lens fiber cell differentiation.

PMID- 15969764
TI  - Treatment failure in a typhoid patient infected with nalidixic acid resistant S.
      enterica serovar Typhi with reduced susceptibility to ciprofloxacin: a case
      report from Cameroon.
AB  - BACKGROUND: Fluoroquinolones or third generation cephalosporins are the drugs of
      choice for the treatment of typhoid fever. Treatment failure with
      fluoroquinolones has been reported in Asia and Europe. We report a case of
      ciprofloxacin treatment failure in typhoid fever in Cameroon. CASE PRESENTATION:
      A 29-year-old female patient with suspected typhoid fever from Kumba, Cameroon,
      yielded growth of Salmonella enterica serovar Typhi in blood culture. The isolate
      was resistant to nalidixic acid but sensitive to ciprofloxacin by disc diffusion
      test. However, the patient did not respond to treatment with ciprofloxacin,
      although the isolate was apparently susceptible to ciprofloxacin. CONCLUSION:
      Treatment failure with ciprofloxacin in our case indicates the presence of
      nalidixic acid resistant S. enterica serovar Typhi (NARST) with reduced
      susceptibility to ciprofloxacin in Cameroon (Central Africa).

PMID- 15969765
TI  - An overview of the design and methods for retrieving high-quality studies for
      clinical care.
AB  - BACKGROUND: With the information explosion, the retrieval of the best clinical
      evidence from large, general purpose, bibliographic databases such as MEDLINE can
      be difficult. Both researchers conducting systematic reviews and clinicians faced
      with a patient care question are confronted with the daunting task of searching
      for the best medical literature in electronic databases. Many have advocated the
      use of search filters or "hedges" to assist with the searching process. The
      purpose of this report is to describe the design and methods of a study that set
      out to develop optimal search strategies for retrieving sound clinical studies of
      health disorders in large electronics databases. OBJECTIVE: To describe the
      design and methods of a study that set out to develop optimal search strategies
      for retrieving sound clinical studies of health disorders in large electronic
      databases. DESIGN: An analytic survey comparing hand searches of 170 journals in
      the year 2000 with retrievals from MEDLINE, EMBASE, CINAHL, and PsycINFO for
      candidate search terms and combinations. The sensitivity, specificity, precision,
      and accuracy of unique search terms and combinations of search terms were
      calculated. CONCLUSION: A study design modeled after a diagnostic testing
      procedure with a gold standard (the hand search of the literature) and a test
      (the search terms) is an effective way of developing, testing, and validating
      search strategies for use in large electronic databases.

PMID- 15969766
TI  - Molecular analysis of two local falciparum malaria outbreaks on the French Guiana
      coast confirms the msp1 B-K1/varD genotype association with severe malaria.
AB  - BACKGROUND: Plasmodium falciparum outbreaks can occur in the coastal area of
      French Guiana, where the population is essentially non-immune. Two sporadic
      outbreaks were observed, including one with severe malaria cases. To characterize
      these outbreaks and verify previous observations of specific genotype
      characteristics in severe malaria in this area, all cases from each outbreak were
      studied. METHODS: P. falciparum genotypes for six genetic loci were determined by
      PCR amplification from peripheral blood parasites. The msp1/block2 and msp2
      genotypes were determined by DNA sequencing. Microsatellite and varD genotyping
      was based on size polymorphism and locus-specific amplification. RESULTS: The
      outbreak including severe malaria cases was associated with a single genotype.
      The other mild malaria outbreak was due to at least five distinct genotypes.
      CONCLUSION: Two distinct types of outbreak occurred despite systematic and
      sustained deployment of malaria control measures, indicating a need for
      reinforced vigilance. The varD/B-K1 msp1 linkage and its association with severe
      malaria in this area was confirmed.

PMID- 15969767
TI  - Modulation of p53 activity by IkappaBalpha: evidence suggesting a common
      phylogeny between NF-kappaB and p53 transcription factors.
AB  - BACKGROUND: In this work we present evidence that the p53 tumor suppressor
      protein and NF-kappaB transcription factors could be related through common
      descent from a family of ancestral transcription factors regulating cellular
      proliferation and apoptosis. P53 is a homotetrameric transcription factor known
      to interact with the ankyrin protein 53BP2 (a fragment of the ASPP2 protein). NF
      kappaB is also regulated by ankyrin proteins, the prototype of which is the
      IkappaB family. The DNA binding sequences of the two transcription factors are
      similar, sharing 8 out of 10 nucleotides. Interactions between the two proteins,
      both direct and indirect, have been noted previously and the two proteins play
      central roles in the control of proliferation and apoptosis. RESULTS: Using
      previously published structure data, we noted a significant degree of structural
      alignment between p53 and NF-kappaB p65. We also determined that IkappaBalpha and
      p53 bind in vitro through a specific interaction in part involving the DNA
      binding region of p53, or a region proximal to it, and the amino terminus of
      IkappaBalpha independently or cooperatively with the ankyrin 3 domain of
      IkappaBalpha In cotransfection experiments, kappaBalpha could significantly
      inhibit the transcriptional activity of p53. Inhibition of p53-mediated
      transcription was increased by deletion of the ankyrin 2, 4, or 5 domains of
      IkappaBalpha Co-precipitation experiments using the stably transfected ankyrin 5
      deletion mutant of kappaBalpha and endogenous wild-type p53 further support the
      hypothesis that p53 and IkappaBalpha can physically interact in vivo. CONCLUSION:
      The aggregate results obtained using bacterially produced IkappaBalpha and p53 as
      well as reticulocyte lysate produced proteins suggest a correlation between in
      vitro co-precipitation in at least one of the systems and in vivo p53 inhibitory
      activity. These observations argue for a mechanism involving direct binding of
      IkappaBalpha to p53 in the inhibition of p53 transcriptional activity, analogous
      to the inhibition of NF-kappaB by kappaBalpha and p53 by 53BP2/ASPP2. These data
      furthermore suggest a role for ankyrin proteins in the regulation of p53
      activity. Taken together, the NFkappaB and p53 proteins share similarities in
      structure, DNA binding sites and binding and regulation by ankyrin proteins in
      support of our hypothesis that the two proteins share common descent from an
      ancestral transcriptional factor.

PMID- 15969768
TI  - Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal
      formulation in alloxan induced hyperglycemic rats.
AB  - BACKGROUND: This study was undertaken to investigation the effect of Diasulin, a
      poly herbal drug composed of ethanolic extract of ten medicinal plants on blood
      glucose, plasma insulin, tissue lipid profile, and lipidperoxidation in alloxan
      induced diabetes. METHODS: Ethanolic extract of Diasulin a, poly herbal drug was
      administered orally (200 mg/kg body weight) for 30 days. The different doses of
      Diasulin on blood glucose and plasma insulin in diabetic rats were studied and
      the levels of lipid peroxides [TBARS, and hydroperoxide] and tissue lipids
      [cholesterol, triglyceride, phospholipides and free fatty acids] were also
      estimated in alloxan induced diabetic rats. The effects were compared with
      glibenclamide. RESULT: Treatment with Diasulin and glibenclamide resulted in a
      significant reduction of blood glucose and increase in plasma insulin. Diasulin
      also resulted in a significant decrease in tissue lipids and lipid peroxide
      formation. The effect produced by Diasulin was comparable with that of
      glibenclamide. CONCLUSION: The decreased lipid peroxides and tissue lipids
      clearly showed the antihyperlipidemic and antiperoxidative effect of Diasulin
      apart from its antidiabetic effect.

PMID- 15969770
TI  - Long-term potentiation in hippocampus involves sequential activation of soluble
      guanylate cyclase, cGMP-dependent protein kinase and cGMP-degrading
      phosphodiesterase, alterations in hyperammonemia.

PMID- 15969769
TI  - transAlign: using amino acids to facilitate the multiple alignment of protein
      coding DNA sequences.
AB  - BACKGROUND: Alignments of homologous DNA sequences are crucial for comparative
      genomics and phylogenetic analysis. However, multiple alignment represents a
      computationally difficult problem. For protein-coding DNA sequences, it is more
      advantageous in terms of both speed and accuracy to align the amino-acid
      sequences specified by the DNA sequences rather than the DNA sequences
      themselves. Many implementations making use of this concept of "translated
      alignments" are incomplete in the sense that they require the user to manually
      translate the DNA sequences and to perform the amino-acid alignment. As such,
      they are not well suited to large-scale automated alignments of large and/or
      numerous DNA data sets. RESULTS: transAlign is an open-source Perl script that
      aligns protein-coding DNA sequences via their amino-acid translations to take
      advantage of the superior multiple-alignment capabilities and speed of an amino
      acid alignment. It operates by translating each DNA sequence into its
      corresponding amino-acid sequence, passing the entire matrix to ClustalW for
      alignment, and then back-translating the resulting amino-acid alignment to derive
      the aligned DNA sequences. In the translation step, transAlign determines the
      optimal orientation and reading frame for each DNA sequence according to the
      desired genetic code. It also checks for apparent frame shifts in the DNA
      sequences and can handle frame-shifted sequences in one of three ways (delete,
      align as amino acids regardless, or profile align as DNA). As a set of
      comparative benchmarks derived from six protein-coding genes for mammals shows,
      the strategy implemented in transAlign always improves the speed and usually the
      apparent accuracy of the alignment of protein-coding DNA sequences. CONCLUSION:
      transAlign represents one of few full and cross-platform implementations of the
      concept of translated alignments. Both the advantages accruing from performing a
      translated alignment and the suite of user-definable options available in the
      program mean that transAlign is ideally suited for large-scale automated
      alignments of very large and/or very numerous protein-coding DNA data sets.
      However, the good performance offered by the program also translates to the
      alignment of any set of protein-coding sequences. transAlign, including the
      source code, is freely available at http://www.tierzucht.tum.de/Bininda-Emonds/
      (under "Programs").

PMID- 15969772
TI  - Complementary therapies for the treatment of HIV: in search of the evidence.
AB  - The use of complementary and alternative medicine (CAM) is widespread. Yet,
      little is known about the evidence supporting its use in HIV/AIDS. We conducted a
      systematic review of randomized clinical trials assessing the effectiveness of
      complementary therapies for HIV and HIV-related symptoms. Comprehensive
      literature searches were performed of seven electronic databases. Data were
      abstracted independently by two reviewers. Thirty trials met our predefined
      inclusion/exclusion criteria: 18 trials were of stress management; five of
      Natural Health Products; four of massage/therapeutic touch; one of acupuncture;
      two of homeopathy. The trials were published between 1989 and 2003. Most trials
      were small and of limited methodological rigour. The results suggest that stress
      management may prove to be an effective way to increase the quality of life. For
      all other treatments, data are insufficient for demonstrating effectiveness.
      Despite the widespread use of CAM by people living with HIV/AIDS, the
      effectiveness of these therapies has not been established. Vis a vis CAM's
      popularity, the paucity of clinical trials and their low methodological quality
      are concerning.

PMID- 15969773
TI  - Comparison of efavirenz and nevirapine in HIV-infected patients (NEEF Cohort).
AB  - The non-nucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz (EFV) and
      nevirapine (NVP) taken in combination with nucleoside reverse transcriptase
      inhibitors (NRTIs) have both shown to be just as highly effective as protease
      inhibitors (PIs) in reducing viral load in patients infected with HIV. Our study
      compares the performance of these two NNRTIs with each other. This was a non
      randomized, prospective, two-arm, multi-centre trial. We evaluated all patients
      with an EFV- or NVP-containing antiretroviral regimen. The primary endpoint was
      the difference in success rates defined as a viral load of </=50 copies/mL at
      week 48. chi(2)-tests were used for naive and pretreated patients using intention
      to-treat (ITT) and on-treatment analysis. As secondary endpoints, a viral load of
      </=500 copies/mL and CD4 count at week 48 for naive patients were evaluated. A
      Cox regression was used to adjust for prespecified covariates. We included 662
      patients (NVP 337, EFV 325). The difference in success rates in the ITT analysis
      was 4.5% ( -11.5%, 19.0%), P=0.578. Pretreated patients with a triple therapy
      show a difference of 10.1 (-0.3, 20.6), P=0.056. Non-significant results appeared
      for all secondary analyses. In this trial, no difference between EFV and NVP in
      combination with NRTI backbone therapy can be shown, regarding viral load.
      Further randomized studies are necessary to evaluate possible differences.

PMID- 15969774
TI  - Health advisor workload.
AB  - Health advisors (HAs) are an integral part of the multidisciplinary team within
      genitourinary (GU) medicine clinics, with a pivotal role in the National Sexual
      Health Strategy by enhancing liaison between community sexual health provision
      and GU medicine services. Greater clarity is needed about HAs' current activities
      and workload in order to enable benchmarking and ensure accurate workforce
      planning. We describe a tool for assessing HA workload and activity and
      evaluating its use in real clinic environments through a prospective time and
      motion model. Ten centres (63% of those invited to participate) within a single
      region did so. Median HA working times were calculated at almost 15 min/patient
      consultation and approximately 10 min/telephone call. Although there were strong
      positive correlations between HA availability and some markers of clinical
      activity, these were weaker than similar correlations applied to medical staff,
      raising the possibility of suboptimal HA workforce planning.

PMID- 15969775
TI  - Verification of clinical samples, positive in AMPLICOR Neisseria gonorrhoeae
      polymerase chain reaction, by 16S rRNA and gyrA compared with culture.
AB  - We compared 956 samples for AMPLICOR Neisseria gonorrhoeae polymerase chain
      reaction (PCR) (Roche) with species verification using the 16S rRNA gene to
      verification using gyrA gene. Control was the culture method. The gyrA
      verification uses pyrosequencing of the quinolone resistance-determining region
      of gyrA. Of 52 samples with optical density >/=0.2 in PCR, 27 were negative in
      culture, two samples from pharynx were false negative in culture and four samples
      from pharynx were false positives in verification with 16S rRNA. Twenty-five
      samples showed growth of gonococci, 18 of the corresponding PCR samples were
      verified by both methods; three urine samples were positive only in gyrA ; and
      one pharynx specimen was positive only in 16S rRNA. Three samples were lost. We
      conclude that AMPLICOR N. gonorrhoeae PCR with verification in gyrA gene can be
      considered as a diagnostic tool in populations with low prevalence of gonorrhoea
      and that pharynx specimens should not be analysed by PCR.

PMID- 15969776
TI  - A drug dosage table is a useful tool to facilitate prescriptions of
      antiretroviral drugs for children in Thailand.
AB  - Scaling up of antiretroviral treatment (ART) for children in countries like
      Thailand will require decentralization and management by non-specialist doctors.
      We describe (a) the formulation of a standardized drug dosage table to facilitate
      antiretroviral drug (ARV) prescriptions for children, (b) the acceptability of
      such a table among doctors and (c) the safety and efficacy of drug doses in the
      table. Acceptability was assessed using a questionnaire. Safety and efficacy were
      assessed on the basis of incidence of adverse effects and virological response to
      treatment, respectively. Of all doctors (n=18), 17 (94%) found that the table was
      practical to use, avoided miscalculations and made them more confident with
      prescriptions. Of 49 children prescribed ARVs, less than 5% had adverse side
      effects. All ARV-naive children achieved undetectable viral loads within six
      months of ART. In our setting, a standardized drug dosage table provided a simple
      and reliable tool that facilitated ARV prescriptions for children.

PMID- 15969777
TI  - Incidence of acute pancreatitis and nucleoside reverse transcriptase inhibitors
      usage.
AB  - Acute pancreatitis (AP) is a well-known adverse effect of nucleoside reverse
      transcriptase inhibitors (NRTIs). Therefore, we performed a prospective, cohort
      study to examine the incidence rates (IRs) and rate ratios (RRs) of AP for each
      NRTI. A total of 116 HIV patients were included in the final analysis comprising
      445.6 person-years of follow-up. Twelve cases of AP were recorded. The lowest IR
      for AP was for didanosine (ddI) (IR=0.03 per 100 person-years, 95% confidence
      interval [CI] = 0.01-0.05), and the highest for ddI + stavudine (d4T) (IR = 0.08,
      95% CI = 0.07-012). Compared with ddI alone, the RR of AP was 2.21 (95% CI = 1.32
      9.31) for d4T, and 3.13 (95% CI = 1.43-12.56) for ddI + d4T. Other risk factors
      for AP were CD4 cell count <200 cells/mm(3) and female sex. Our results suggest
      that the use of d4T alone or combined with ddI should not be used as first-line
      therapy, especially in women or patients with CD4-cell count <200 cells/mm(3).

PMID- 15969778
TI  - Molecular testing (strand displacement assay) for identification of urethral
      gonorrhoea in men: can it replace culture as the gold standard?
AB  - The objective was to evaluate the performance of Becton Dickinson's BD Probe
      Tec(TM) (BDPT) strand displacement amplification (SDA) test for the detection of
      Neisseria gonorrhoeae on urethral specimens from men with urethritis compared
      with conventional culture and to show that SDA improves the diagnostic yield of
      gonorrhoea infections (GC). Anonymized retrospective testing of stored urethral
      swab samples from men attending genitourinary services in East London was
      performed using SDA. The prevalence of GC culture positive infections in this
      sample was 20/152 (13%). The sensitivity, specificity, positive predictive value
      and negative predictive value for the BDPT-SDA system compared with culture were
      100%, 95%, 77% and 100%, respectively. In this study population, the BDPT-SDA
      assay was a highly sensitive and specific test for the diagnosis of N.
      gonorrhoeae from urethral swabs in men. Therefore, SDA can be used to complement
      culture in the diagnosis of N. gonorrhoeae infection. No ethics committee
      approval was obtained as all samples were anonymized.

PMID- 15969779
TI  - A care pathway for chlamydia, what's happening in primary care 12 months on?
AB  - Primary care is seen as central to the future provision of sexual health
      services, including chlamydia screening. The aim of this study was to establish
      levels of awareness and application of a chlamydia care pathway among practice
      nurses in primary care 12 months after its launch and present knowledge and
      practice of testing. Questionnaires were sent to 46 practice nurses at 22 general
      practitioner practices within the care pathway pilot site. Response rate was
      33/46 (72%), with 30 (94%) practice nurses aware of the care pathway and 19 (62%)
      routinely using it. Endocervical swabbing was performed by 29 (90%) respondents,
      no endourethral swabs were taken from men and 85% nurses did not perceive partner
      notification as being part of their role. Practice nurses identified the need for
      training in using the care pathway and in identification of infection to optimize
      the provision of effective sexual health care in primary care.

PMID- 15969780
TI  - Clinical value of C-reactive protein measurements in HIV-positive patients.
AB  - The acute-phase protein C-reactive protein (CRP) is a sensitive marker of
      inflammation and tissue damage. We measured CRP in 109 HIV-1 antibody-positive
      patients admitted to hospital for investigation. In 67 patients with intercurrent
      infection (of whom 27 were afebrile at presentation) CRP levels were 2.2-483.5
      mg/dL (normal value in the general population <3 mg/dL) and in 42 patients with
      alternative non-infection diagnoses CRP levels were 0.5-108.6 (median=5.9) mg/dL.
      Whereas in those with infections elevated CRP levels fell in response to specific
      therapy, values remained abnormal in those with non-infection diagnoses. CRP
      appears useful for diagnosis and monitoring of intercurrent infection in HIV-1
      antibody-positive patients. In HIV-1 antibody-positive patients without
      intercurrent infection, CRP values higher than in the general population possibly
      reflect a sustained acute-phase response as a consequence of HIV infection per
      se.

PMID- 15969781
TI  - HIV in couples in South India; implications for prevention.
AB  - We studied HIV prevalence in couples in Chennai, India. In 56% both partners were
      infected. Among discordant couples, 35 men and seven women were infected.
      Heterosexual intercourse is the primary risk factor. Concordance was related to
      sex with commercial sex workers for men and to genital ulcer disease for women.
      Median CD4 count was 97 cells/mm(3) among concordant men, 222 cells/mm(3) among
      discordant men. Condom use increased, and frequency of sexual intercourse
      decreased, among all couples after HIV diagnosis.

PMID- 15969782
TI  - Clinical audit: adherence to sexually transmitted infection screening guidelines
      for men who have sex with men.
AB  - Australian guidelines recommend regular screening of men who have sex with men
      (MSM) for sexually transmitted infections (STIs). This audit was performed to
      determine STI testing rates in Sydney Sexual Health Centre before and after the
      development of the guidelines, and to describe characteristics of those not
      tested. The electronic clinic database and a manual file review were used to
      determine testing rates and reasons for not testing for the years 2000 and 2002.
      Overall testing rates were high, with 61% of MSM having had all recommended tests
      within the past year in 2002. There was a significant increase in testing rates
      for most tests after the development of the guidelines. Asymptomatic men were
      more likely to be tested than symptomatic men, and HIV-positive men were less
      likely to be tested for syphilis.

PMID- 15969783
TI  - Audit of offering HIV testing in the genitourinary medicine clinic in Aberystwyth
      in 2003.
AB  - The introduction of the Genitourinary (GU) Medicine Good Clinical Care, Standard
      2 of offering HIV testing is discussed. The results of an audit of the
      Aberystwyth GU medicine clinic against that Standard in 2003 are presented. Of
      new patients screened for sexually transmitted infections, 97.5% had been offered
      HIV testing and the uptake had been 70.3%.

PMID- 15969784
TI  - Staphylococcus sciuri: an unusual cause of pelvic inflammatory disease.
AB  - We present the case of polymicrobial pelvic inflammatory disease (PID) that
      involved Staphylococcus sciuri, S. epidermidis, and Streptococcus agalactiae. In
      order to determine the frequency of S. sciuri isolation from the female lower
      genital tract, 3415 vaginal samples were analysed during the one-year study
      period. S. sciuri was isolated from three (0.09%) samples. In all the three
      cases, S. sciuri was obtained in mixed culture from outpatients without symptoms
      of infection. While the origin of S. sciuri in the female genital tract remains
      to be elucidated, the present study showed that this bacterium may colonize
      vagina and, moreover, may be involved in the pathogenesis of an infection as
      serious as PID. The low rate of isolation we established, however, indicates
      infrequent and, most probably, transient colonization of the female genital tract
      by S. sciuri.

PMID- 15969785
TI  - Chronic vulval ulceration--another immune reconstitution inflammatory syndrome?
AB  - We describe a patient who developed intractable chronic vulval ulceration that we
      believe was related to immune reconstitution following treatment of HIV infection
      with highly active antiretroviral treatment (HAART). Immune reconstitution
      inflammatory syndrome should be considered in the differential diagnosis of
      unexplained vulval ulceration that arises after starting HAART.

PMID- 15969786
TI  - Asymptomatic urethritis; the case for a considered view.

PMID- 15969787
TI  - Protecting the future of sexual health services: lessons from the retail
      industry.

PMID- 15969788
TI  - Mobile post-HIV test counselling.

PMID- 15969789
TI  - Active detection of men with asymptomatic chlamydial or gonorrhoeal urethritis.

PMID- 15969790
TI  - Emerging trends in ocular telemedicine: the diabetic retinopathy model.
AB  - Diabetes mellitus is a leading cause of vision loss in industrialized countries.
      Diabetic retinopathy has features which make it ideal for disease management by
      telemedicine. The American Telemedicine Association (ATA) has recently
      established consensus recommendations for ocular telemedicine for diabetic
      retinopathy, in cooperation with the US National Institute of Standards and
      Technology. The guiding principle is that it would be inappropriate to use
      telemedicine to provide anything less than the accepted standard of clinical
      care. The ATA practice recommendations delineate performance standards for the
      clinical, technical and administrative elements of ocular telemedicine for
      diabetic retinopathy. Four clinical categories of assessment were identified.
      Category 4 validation, for example, indicates that a system matches or exceeds
      the ability of current photographs to identify lesions of diabetic retinopathy.
      To create the practice recommendations, workshops were held to address each of
      the three components: (1) clinical, (2) technical, and (3) operational and
      business. Ocular telemedicine programmes will need to demonstrate sustainability
      and cost-effectiveness, and respect a patient's right to privacy. Nevertheless,
      ocular telemedicine seems poised to become an integral part of eye health care,
      as long as programmes meet or exceed present clinical standards of care, and
      patient and provider expectations are clearly defined.

PMID- 15969791
TI  - Evaluating telemedicine systems and services.
AB  - The evaluation of telemedicine involves attempts to answer a wide range of
      questions involved in making decisions about safety, about practicality and about
      utility. Roughly speaking, if we wish to provide a telemedicine service we should
      first establish that it is safe, next that it is practical and finally that it is
      worthwhile. In establishing safety, most laboratory studies of telemedicine have
      a common structure, and consist of the following steps: (1) selection of cases;
      (2) interpretation; (3) comparison with a gold standard; (4) statistical
      analyses. Most of the studies to establish the practicality of telemedicine have
      been carried out as demonstrations, to show that a proposed application can be
      implemented in a chosen setting. In terms of utility, telemedicine has been used
      to improve the efficiency of an existing service or to make an existing service
      available to a new community. One of the difficulties is that the vendors of
      relatively expensive telemedicine systems and services disseminate much of the
      information on the topic. We have to focus not on the glamorous technology but on
      the underlying issue of how the participants in health care (patients, general
      practitioners, specialists) can communicate more effectively, using the range of
      technological options open to them. Ensuring that the most appropriate technology
      is used in the most effective way should be the primary aim of telemedicine
      research. There is now sufficient evidence for us to be confident that
      telemedicine is a safe alternative to conventional care in a variety of
      situations and for a number of clinical conditions. Reliable evidence that it is
      a practical and cost-effective alternative is, at the time of writing, harder to
      find.

PMID- 15969792
TI  - Evaluation of the benefits for the patient arising from an inter-hospital
      teleradiology network in a French administrative area.
AB  - We conducted a prospective study of the teleradiology network which connects 15
      hospitals in the Aquitaine area. All transmissions sent over a one-year period
      were examined (data transmitted at the time of the remote consultation and health
      outcomes of patients from their medical records). For emergency cases, the main
      outcome measure of effectiveness was the proportion of avoided transfers. For non
      emergency cases, the main outcome measure of effectiveness was the proportion of
      transfers, hospitalizations and consultations avoided. There were 737
      transmissions, of which 664 (90%) met the inclusion criteria. Of these, 562 (85%)
      were for emergency care and 102 (15%) for non-emergency care. In emergency care,
      the pathologies most often associated with a remote consultation were cerebral
      pathologies (88%) and traumatic spinal pathologies (8%); the proportion of
      avoided transfers was 48%. In non-emergency care, the specialties most often
      concerned with remote consultations were neurology/neurosurgery (36%), cardiology
      and pulmonary diseases (17%) and gastroenterology (14%). Transfer was avoided for
      37% of the patients and hospitalization for 12%. An additional consultation
      occurred after remote consultation for 2% of the patients. The results confirm
      the effectiveness of an inter-hospital teleradiology network.

PMID- 15969793
TI  - Telephonic transmission of 12-lead electrocardiograms during acute myocardial
      infarction.
AB  - To test the feasibility of a small and simple system for telephonic transmission
      of 12-lead electrocardiograms (ECGs), 70 patients with acute coronary syndrome
      admitted to the cardiac care unit (CCU) were included in a feasibility study. The
      transmission system consisted of a belt with multiple electrodes, which was
      positioned around the chest. The ECG signal was sent to a call centre via a
      standard telephone line. In parallel, a standard 12-lead ECG was recorded on
      site. In a retrospective analysis, each lead of the transmitted ECG was compared
      with the on-site 12-lead ECG with regard to ST-segment changes and final
      diagnosis. In all 37 patients with acute ST-elevation myocardial infarction, the
      diagnosis was correctly established on the basis of telephone-transmitted ECGs.
      In 96% of limb and 88% of chest leads, ST elevations which were visible in
      standard ECGs were correctly displayed on telephonically transmitted ECGs. In the
      remaining 33 patients no false-positive diagnosis was made using transtelephonic
      ECG analysis. A control group of 31 patients without apparent heart disease
      showed high concordance between standard ECGs and telephonically transmitted
      ECGs. Telephonically transmitted 12-lead ECGs interpreted by a hospital-based
      internist/cardiologist might allow a rapid and accurate diagnosis of ST-elevation
      myocardial infarction and may increase diagnostic safety for the emergency staff
      during prehospital decision making and treatment of acute myocardial infarction.

PMID- 15969794
TI  - Low-bandwidth telemedicine for pre- and postoperative evaluation in mobile
      surgical services.
AB  - Low-bandwidth telemedicine was used for the pre- and postoperative evaluation of
      patients treated by a mobile surgery service in remote Ecuador. Realtime and
      store-and-forward telemedicine was employed, using PCs connected via the ordinary
      telephone network. Between February 2002 and July 2003, 144 patients were studied
      preoperatively and 50 postoperatively. It was possible to establish 20
      satisfactory preoperative realtime connections, which allowed good-quality,
      simultaneous audiovisual transmission. Thus, there were 124 preoperative
      assessments done by store-and-forward telemedicine and 50 postoperative
      assessments. Diagnoses and management plans made by a surgeon using telemedicine
      were compared with those made independently by a second surgeon, who saw the
      patient face to face. Due to poor quality of the transmitted images, 43 patients
      were excluded from the preoperative study and 13 from the postoperative study. In
      the 101 preoperative evaluations, there was agreement in 78 cases (77%); in the
      37 postoperative evaluations, there was agreement in 36 cases (97%). Telemedicine
      may reduce the time required on site for preoperative planning, and may provide
      reliable postoperative surveillance, thus improving the efficiency of mobile
      surgery services.

PMID- 15969795
TI  - An intelligent emergency response system: preliminary development and testing of
      automated fall detection.
AB  - We have designed an intelligent emergency response system to detect falls in the
      home. It uses image-based sensors. A pilot study was conducted using 21 subjects
      to evaluate the efficacy and performance of the fall-detection component of the
      system. Trials were conducted in a mock-up bedroom setting, with a bed, a chair
      and other typical bedroom furnishings. A small digital videocamera was installed
      in the ceiling at a height of approximately 2.6 m. The digital camera covered an
      area of approximately 5.0 m x 3.8 m. The subjects were asked to assume a series
      of postures, namely walking/standing, sitting/lying down in an inactive zone,
      stooping, lying down in a 'stretched' position, and lying down in a 'tucked'
      position. These five scenarios were repeated three times by each subject in a
      random order. These test positions totalled 315 tasks with 126 fall-simulated
      tasks and 189 non-fall-simulated tasks. The system detected a fall on 77% of
      occasions and missed a fall on 23%. False alarms occurred on only 5% of
      occasions. The results encourage the potential use of a vision-based system to
      provide safety and security in the homes of the elderly.

PMID- 15969796
TI  - The use of email in a child and adolescent mental health service: are staff
      ready?
AB  - All staff members of a child and adolescent mental health service were invited to
      participate in a survey about the use of email. Sixty-two of the 105 staff
      members responded to the survey, a participation rate of 59%. Of the respondents,
      32 were allied health staff, 10 were nurses, seven were administrative staff, six
      were medical staff, three were operational staff and four were acting in a
      combination of these roles. The respondents reported extensive work-related email
      usage and considered that they were confident in using email despite low levels
      of training. However, they did not feel that they understood the legal and
      ethical issues involved. Furthermore, there was limited incorporation of email
      into standard record keeping. The majority of respondents thought that increased
      use of email would lead to a greater workload, a consequence they considered
      would probably increase over time. Many commented on the quick and practical use
      of this medium, but were wary about using email with individuals outside the
      service organization, especially if it were to contain clinical material. There
      was low use of email directly with clients, and clinicians were ambivalent about
      incorporating email into therapy. The results suggest that it is timely to
      consider the utility and appropriateness of email communication with clients and
      external service providers, and to formulate guidelines and procedures to ensure
      the confidentiality of client information and the safety of clients and staff.

PMID- 15969797
TI  - Use of telephone interviews to follow up patients after total hip replacement.
AB  - We studied the feasibility of telephone interviews to assess hip function in
      patients who had had a total hip replacement. One hundred patients attending the
      orthopaedic clinic for follow-up after undergoing total hip replacement were
      studied. A modified Harris hip score was used. Since range of motion and
      deformity cannot be assessed by telephone, only pain and function were assessed.
      The maximum possible score was 100. Patients attending follow-up clinics were
      contacted by telephone one to two weeks prior to their appointment and a
      telephone assessment was completed. This was then compared with a face-to-face
      assessment in the subsequent clinic. The mean hip score obtained with the
      telephone interview was 85.2 and the mean hip score at face-to-face assessment
      was 86.1. The mean of the differences between the individual scores was -0.9 (SD
      5.5). This difference was not significant ( P=0.11). Only three patients had a
      clinically significant difference (>20 points) between the two methods. Telephone
      questionnaires may be a useful adjunct to face-to-face assessment for patient
      follow-up after total hip replacement.

PMID- 15969799
TI  - Bell's first telephone call--not the first telemedicine consultation.

PMID- 15969801
TI  - Investigation of selected baseline removal techniques as candidates for automated
      implementation.
AB  - Observed spectra normally contain spurious features along with those of interest
      and it is common practice to employ one of several available algorithms to remove
      the unwanted components. Low frequency spurious components are often referred to
      as 'baseline', 'background', and/or 'background noise'. Here we examine a cross
      section of non-instrumental methods designed to remove background features from
      spectra; the particular methods considered here represent approaches with
      different theoretical underpinnings. We compare and evaluate their relative
      performance based on synthetic data sets designed to exemplify vibrational
      spectroscopic signals in realistic contexts and thereby assess their suitability
      for computer automation. Each method is presented in a modular format with a
      concise review of the underlying theory, along with a comparison and discussion
      of their strengths, weaknesses, and amenability to automation, in order to
      facilitate the selection of methods best suited to particular applications.

PMID- 15969802
TI  - Enhancement of infrared spectral images for maximizing chemical information by
      minimizing baseline interferences.
AB  - The popularity of spectral images in many areas of analysis has greatly increased
      during the last decade due to the development of charge-coupled device (CCD) and
      infrared sensitive cameras. Large amounts of spatial information can be obtained
      in short periods of time. The general goal in analytical chemistry is to convert
      spectral images into chemical images, which show the spatial locations of various
      chemical components. Self-modeling multivariate curve resolution methods can be
      used to extract pure component spectra from the mixture spectra in images and
      produce chemical images. However, there is a difficulty in processing infrared
      spectral images due to large pixel-to-pixel baseline variations. Herein, a method
      for minimizing baseline interferences using fast Fourier transform (FFT)
      filtering in both the spectral and spatial domains is discussed. The methodology
      is demonstrated on a microscopic sample of butter contaminated with non
      pathogenic E. coli and on a cross-sectional sample of rabbit aorta containing
      plaque. The processing to reduce baseline effects improved the spatial resolution
      without compromising the spectral resolution.

PMID- 15969803
TI  - A general computational method for converting normal spectra into derivative
      spectra.
AB  - The mathematical problem of converting a normal spectrum into the corresponding
      first- and second-derivative spectra is formulated as an integral equation of the
      first kind. Tikhonov regularization is then applied to solve the spectral
      conversion problem. The end result is a set of linear algebraic equations that
      takes in as input the original spectrum and produces as output the second
      derivative spectrum, which is then integrated to yield the first-derivative
      spectrum. Noise amplification is kept under control by adjusting the
      regularization parameter (guided by generalized cross-validation) in the
      algebraic equations. The performance of this procedure is demonstrated by
      applying it to different types of spectral data taken from the literature.

PMID- 15969804
TI  - Detection of apple juice adulteration using near-infrared transflectance
      spectroscopy.
AB  - Near-infrared transflectance spectroscopy was used to detect adulteration of
      apple juice samples. A total of 150 apple samples from 19 different varieties
      were collected in two consecutive years from orchards throughout the main
      cultivation areas in Ireland. Adulterant samples at 10, 20, 30, and 40% w/w were
      prepared using two types of adulterants: a high fructose corn syrup (HFCS) with
      45% fructose and 55% glucose, and a sugars solution (SUGARS) made with 60%
      fructose, 25% glucose, and 15% sucrose (the average content of these sugars in
      apple juice). The results show that NIR analysis can be used to predict
      adulteration of apple juices by added sugars with a detection limit of 9.5% for
      samples adulterated with HFCS, 18.5% for samples adulterated with SUGARS, and 17%
      for the combined (HFCS + SUGARS) adulterants. Discriminant partial least squares
      (PLS) regression can detect authentic apple juice with an accuracy of 86-100% and
      adulterant apple juice with an accuracy of 91-100% depending on the adulterant
      type and level of adulteration considered. This method could provide a rapid
      screening technique for the detection of this type of apple juice adulteration,
      although further work is required to demonstrate model robustness.

PMID- 15969805
TI  - Prediction of ethylene content in melt-state random and block polypropylene by
      near-infrared spectroscopy and chemometrics: influence of a change in sample
      temperature and its compensation method.
AB  - This paper reports on the influence of a change in sample temperature, and a
      method for its compensation, for the prediction of ethylene (C2) content in melt
      state random polypropylene (RPP) and block polypropylene (BPP) by near-infrared
      (NIR) spectroscopy and chemometrics. Near-infrared (NIR) spectra of RPP in the
      melt and solid states were measured by a Fourier transform near-infrared (FT-NIR)
      on-line monitoring system and an FT-NIR laboratory system. There are some
      significant differences between the solid and melt-state RPP spectra. Moreover,
      we investigated the predicted values of the C2 content from the RPP or BPP
      spectra measured at 190 degrees C and 250 degrees C using the calibration model
      for the C2 content developed using the RPP or BPP spectra measured at 230 degrees
      C. The errors in the predicted values of the C2 content depend on the
      pretreatment methods for each calibration model. It was found that multiplicative
      signal correction (MSC) is very effective in compensating for the influence of
      the change of temperature for the RPP or BPP samples on the predicted C2 content.
      From the suggestion of principal component analysis (PCA) and difference spectrum
      analysis, we propose a new compensation method for the temperature change that
      uses the difference spectra between two spectra sets measured at different
      temperatures. We achieved good results using the difference spectra between the
      RPP/BPP spectra sets measured at 190 degrees C and 250 degrees C after correction
      and the calibration model developed with the spectra measured at 230 degrees C.
      The comparison between the method using MSC and the proposed method showed that
      the predicted error in the latter is slightly better than those in the former.

PMID- 15969806
TI  - Vibrational spectroscopic and ultrasound analysis for in-process characterization
      of high-density polyethylene/polypropylene blends during melt extrusion.
AB  - Spectroscopic techniques such as Raman, mid-infrared (MIR), and near-infrared
      (NIR) have become indispensable analytical tools for rapid chemical quality
      control and process monitoring. This paper presents the application of in-line
      Fourier transform near-infrared (FT-NIR) spectroscopy, Raman spectroscopy, and
      ultrasound transit time measurements for in-line monitoring of the composition of
      a series of high-density polyethylene (HDPE)/polypropylene (PP) blends during
      single-screw extrusion. Melt composition was determined by employing univariate
      analysis of the ultrasound transit time data and partial least squares (PLS)
      multivariate analysis of the data from both spectroscopic techniques. Each
      analytical technique was determined to be highly sensitive to changes in melt
      composition, allowing accurate prediction of blend content to within +/- 1% w/w
      (1sigma) during monitoring under fixed extrusion conditions. FT-NIR was
      determined to be the most sensitive of the three techniques to changes in melt
      composition. A four-factor PLS model of the NIR blend spectra allowed
      determination of melt content with a standard prediction error of +/- 0.30% w/w
      (1sigma). However, the NIR transmission probes employed for analysis were
      invasive into the melt stream, whereas the single probes adopted for Raman and
      ultrasound analysis were noninvasive, making these two techniques more versatile.
      All three measurement techniques were robust to the high temperatures and
      pressures experienced during melt extrusion, demonstrating each system's
      suitability for process monitoring and control.

PMID- 15969807
TI  - Mechanism of thermal phase transition of a ferroelectric liquid crystal with
      monotropic transition temperature studied by infrared spectroscopy combined with
      principal component analysis and sample-sample two-dimensional correlation
      spectroscopy.
AB  - Infrared (IR) spectra of FLC-154 (FLC: ferroelectric liquid crystal) with
      monotropic phase transition under a nonalignment state with a sample layer
      thickness of 24.5 microm were measured for heating process from 55 to 90 degrees
      C and a cooling process from 90 to 55 degrees C in increments of 1 degrees C. The
      thermal dynamics of FLC-154 were investigated by use of IR spectroscopy combined
      with principal component analysis (PCA) and sample-sample two-dimensional (2D)
      correlation spectroscopy. During the cooling, the FLC-154 molecule passes through
      the monotropic smectic-C* (Sm-C*) phase, which is transformed from the Sm-A
      phase. The results from PCA suggest that during the heating process, the thermal
      dynamics of the alkyl chains, core moiety, and C=O groups are similar to each
      other. Furthermore, PCA and sample-sample 2D correlation spectroscopy indicate
      that the alkyl chains and C=O groups in the chiral and core moieties are
      responsible for the emergence of the Sm-C* phase. This conclusion is very
      important because the IR data have given more evident cause for the emergence of
      the Sm-C* phase than the theoretical models such as the molecular-statistical
      theory of ferroelectric ordering and the indigenous polarization theory.
      Moreover, it has been found that some of the trans conformations of the alkyl
      chains of FLC-154 change partly to the gauche conformation when the phase
      transition from the crystalline phase to the Sm-A phase occurs. It has also been
      found that the intermolecular interactions of the C=O group in the core moiety in
      the Sm-A phase are weaker than those in the crystalline phase and that the
      conformational change occurs on the C-O-C bonds in the core moiety upon going
      from the crystalline to the Sm-A phase.

PMID- 15969808
TI  - Analyzing Raman maps of pharmaceutical products by sample-sample two-dimensional
      correlation.
AB  - Sample-sample (SS) two-dimensional (2D) correlation spectroscopy is applied in
      this study as a spectral selection tool to produce chemical images of real-world
      pharmaceutical samples consisting of two, three, and four components. The most
      unique spectra in a Raman mapping spectral matrix are found after analysis of the
      covariance matrix. (This is obtained by multiplying the original mapping data
      matrix by itself.) These spectra are identified by analyzing the slices of the
      covariance matrix at the positions where covariance values are at maxima.
      Chemical images are subsequently produced in a univariate fashion by visually
      selecting the wavenumbers in the extracted spectra that are least overlapped. The
      performance of SS 2D correlation is compared with principal component analysis in
      terms of highlighting the most prominent spectral differences across the whole
      data set (which typically comprises several thousand spectra) and determining the
      total number of species present. In addition, the selection of the unique spectra
      by SS 2D correlation is compared with the selection obtained by the orthogonal
      projection approach (OPA). Both comparisons are found to be satisfactory and
      demonstrate that a quite simple SS 2D correlation routine can be used for
      producing reliable images of unknown samples. The main benefit of using SS 2D
      correlation is that it is based on a few data processing commands that can be
      executed separately and produce results that are closely related to the chemical
      features of the system.

PMID- 15969809
TI  - Characterization of MBa2Cu3O7-x thin films by Raman microspectroscopy.
AB  - Thin film embodiments of MBa2Cu3O7-x (MBCO, M = yttrium or a rare-earth metal)
      prepared by several different deposition methods on a variety of substrates were
      investigated by Raman microspectroscopy. Several of the unique characterization
      capabilities of Raman spectroscopy in the analysis of MBCO thin films are
      highlighted by the results of these investigations. The Raman active phonons of
      the orthorhombic and tetragonal forms of MBCO that are most useful for
      characterization of textured MBCO films are diagrammed and discussed. A rapid
      procedure for qualitative texture mapping of MBCO thin films using Raman
      microscopy techniques is presented, and a new approach for investigating phase
      separation at the sub-micrometer level in MBCO thin films based on curve
      resolution of the MBCO Cu2 phonon is described. The assignment of a particular
      feature often observed in Raman spectra of MBCO films to cation disorder is
      reinforced by results of a cation substitution study. The depth of penetration of
      the laser into MBCO films and the type of information that can be obtained by
      varying the extent of defocusing of the laser are also discussed.

PMID- 15969810
TI  - Raman scattering spectroscopic study of n-pentane under high pressure.
AB  - The Raman spectroscopy of n-pentane was investigated in a Moissanite anvil cell
      from 0.07 GPa to 4.77 GPa at ambient temperature. The result shows that the CH3
      symmetric stretching vibration (2877 cm(-1)) and asymmetric stretching vibration
      (2964 cm(-1)), the CH2 symmetric stretching vibration (2856 cm(-1)) and
      asymmetric stretching vibration (2935 cm(-1)), and -(CH2)n- in-phase twist mode
      (1303 cm(-1)) shifted to higher wavenumbers almost linearly with increasing
      pressure. Around 2.4 GPa an abrupt visible change took place, indicating a sort
      of phenomenon of freezing due to over-pressurization. In the pressure range of
      2.84 to 4.77 GPa a high-pressure phase transition may occur in the crystallized n
      pentane. By determining pressure with the method of solid-liquid coexistence, we
      concluded that the equilibrium freezing pressure of n-pentane is 1.90 +/- 0.05
      GPa at 27 degrees C.

PMID- 15969811
TI  - Surface-enhanced Raman spectra of VX and its hydrolysis products.
AB  - Detection of chemical agents as poisons in water supplies not only requires
      microg/L sensitivity, but also requires the ability to distinguish their
      hydrolysis products. We have been investigating the ability of surface-enhanced
      Raman spectroscopy (SERS) to detect chemical agents at these concentrations. Here
      we expand these studies and present the SERS spectra of the nerve agent VX (ethyl
      S-2-diisopropylamino ethyl methylphosphonothioate) and its hydrolysis products,
      ethyl S-2-diisopropylamino methylphosphonothioate, 2(diisopropylamino)
      ethanethiol, ethyl methylphosphonic acid, and methylphosphonic acid. Vibrational
      mode assignments for the observed SERS peaks are also provided. Overall, each of
      these chemicals produces a series of peaks between 450 and 900 cm(-1) that are
      sufficiently unique to allow identification. SERS measurements were performed in
      silver-doped sol-gel-filled capillaries that are being developed as part of an
      extractive point sensor.

PMID- 15969812
TI  - Influence of the metal film thickness on the sensitivity of surface plasmon
      resonance biosensors.
AB  - The influence of the metal film thickness (i.e., the chromium adhesion promoting
      film and the gold film) on the sensitivity of surface plasmon resonance (SPR)
      signals (i.e., resonance angle shift and reflectance change) towards the
      thickness variation of the nonabsorbing dielectric film is investigated. The
      sensitivity of reflectance change decreases when a thick chromium film or a thin
      gold film is employed. Its linear range becomes narrower as the thickness of the
      metal films increases. The sensitivity and linear range of the resonance angle
      shift are not affected by the thickness variation of the metal films. The
      phenomena were theoretically explained based on the attenuated total reflection
      (ATR) generated evanescent field at the prism/metal interface and the SPR
      generated evanescent field at the metal/dielectric interface.

PMID- 15969813
TI  - Adsorption density of spherical cetyltrimethylammonium bromide (CTAB) micelles at
      a silica/silicon surface.
AB  - In situ Fourier transform infrared internal reflection spectroscopy (FT-IR/IRS)
      was used to calculate the adsorption density values for spherical
      cetyltrimethylammonium bromide (CTAB) micelles at the silica/silicon (SiO2/Si)
      surface based on a previously developed adsorption density equation. Recent
      advances in atomic force microscopy (AFM) imaging methodology have led to the
      ability to image surface micelles, which was not possible previously. These AFM
      images have been used to independently calculate adsorption density values
      through offline fast Fourier transform (FFT) analysis. The adsorption density
      values measured from in situ FT-IR/IRS spectra and from AFM images showed good
      agreement and provide further validation of the FT-IR/IRS adsorption density
      equation in the low concentration range.

PMID- 15969814
TI  - Film techniques for vibrational circular dichroism measurements.
AB  - Vibrational circular dichroism (VCD) spectra in the 1800-900 cm(-1) region have
      been measured recently for protein films and for carbohydrate films prepared from
      aqueous solutions. In addition to the advantages of avoiding the interference
      from strong infrared absorption of water at 1650 cm(-1) and requiring a two
      orders-of-magnitude-smaller amount of sample for film measurements (than those
      required for the same in water solutions), the VCD bands in film measurements are
      found to be the same as those in solution measurements and to be independent of
      film orientation. This latter observation indicated the possibility for routine
      VCD measurements in the film state. In this manuscript we report different film
      techniques for VCD measurements. These techniques include preparation of
      supported films, free-standing films, film-on-film, and facilitation of film
      formation for substances that otherwise do not form amorphous films. The
      experimental data for films prepared by each of these techniques are presented
      and the relative merits of these different methods are discussed.

PMID- 15969815
TI  - Spectroscopic study of a novel bis(heptamethine cyanine) dye and its interaction
      with human serum albumin.
AB  - A newly synthesized near-infrared (NIR) bis(heptamethine cyanine) dye 7 was
      evaluated for its utility as a non-covalent label for proteins. This dye forms
      inter- and intramolecular H-aggregates in polar solvents, even at very low
      concentrations. The intramolecular dimeric form of the dye can be described as a
      clam-shell complex with two interacting hydrophobic carbocyanine moieties. In
      this intramolecular H-aggregate, the chromophore has a low extinction coefficient
      and low fluorescence quantum yield. In aqueous solution, in the absence of human
      serum albumin (HSA), dye 7 has characteristic absorption bands at 792 and 435 nm,
      and its fluorescent emission is significantly diminished in comparison to that in
      methanol or when compared to its monomeric equivalent 5. Dye 7 seems to be more
      advantageous than its monomeric counterpart 5 as a non-covalent label for
      biomolecules. Upon addition of HSA, the H and D bands are decreased and the
      monomeric band is increased, with concomitant increase in fluorescence intensity,
      suggesting that clam-shell H-aggregates open up in the complex with HSA. The
      binding stoichiometry is 1:1. The main advantage of this dimeric dye as a non
      covalent label is that the free dye has negligible fluorescence.

PMID- 15969816
TI  - Binding properties of 2-acetylnaphthalene with hydroxypropyl cyclodextrins from
      fluorescence quenching experiments.
AB  - The quenching of 2-acetylnaphthalene (2-AN) fluorescence by hydroxypropyl
      cyclodextrins (HP-CD) has been analyzed using modified Stern-Volmer plots to
      obtain binding constants as a function of temperature for 2-AN:HP-CD complexes.
      The HP-CDs were commercially available and contained 4-7 HP groups per CD
      molecule for alpha-CD, beta-CD, and gamma-CD. HP substitution causes a 12 to over
      40% increase in binding constant (K(ave)) for 2-AN compared to that for
      unsubstituted CDs, although the K(ave) value is not strongly dependent on the
      extent of HP substitution for beta-CD. No evidence of formation of a 2:2 complex,
      such as that observed with 2-AN and gamma-CD, is observed with 2-AN and HP-gamma
      CD. Thermodynamic parameters (DeltaH degrees and DeltaS degrees ) suggest that
      the increase in K(ave) with HP substitution is due to an enlarged binding site
      for the HP-CDs that allows greater motional freedom for 2-AN. Comparison is made
      to the binding of 2-methylnaphthoate (2-MN) to CDs and HP-CDs, and the larger
      K(ave) values for 2-MN over 2-AN are attributed to greater dispersion forces for
      2-MN complex formation.

PMID- 15969817
TI  - Cobalt speciation study in the cobalt-cysteine system by electrospray ionization
      mass spectrometry and anion-exchange chromatography inductively coupled plasma
      atomic emission spectrometry.
AB  - This paper describes the ability of the combination of electrospray ionization
      mass spectrometry (ESI-MS) and anion-exchange chromatography coupled with
      inductively coupled plasma atomic emission spectrometry (AEC-ICP-AES) for cobalt
      speciation study in the binary cobalt-cysteine system. ESI-MS, allowing the
      identification and the characterization of the analytes, is used as a technique
      complementary to AEC-ICP-AES, providing elemental information on the separated
      species. The methods have been developed through the study of samples containing
      Co2+ and 1-fold to 5-fold molar ratios of cysteine over a pH range 2.5 to 11. In
      each case, cobalt-cysteine complexes were characterized by ESI-MS in negative ion
      mode. AEC-ICP-AES allowed further separation and detection of the cobalt species
      previously characterized. The strong influence of pH and ligand-to-metal ratios
      on the nature and stoichiometry of the species is demonstrated. For the first
      time, a direct experimental speciation diagram of cobalt species has been
      established owing to these analytical techniques. This work is a promising basis
      for the speciation analysis of cobalt, since a good knowledge of cobalt
      speciation is of prime importance to better understanding its fate in biological
      and environmental media.

PMID- 15969827
TI  - Perceptual adaptation affects attractiveness of female bodies.
AB  - We investigated whether short durations (5 minutes) of exposure to distorted
      bodies can change subsequent perceptions of attractiveness and normality.
      Participants rated 110 female bodies, varying in width, on either their
      attractiveness or normality before and after exposure to either extremely narrow
      (-50% of original width in Experiments 1 and 2) or extremely wide bodies (+50% of
      original width in Experiment 1, and +70% of original width in Experiment 2). In
      both experiments, the most attractive and most normal looking bodies became
      significantly and substantially narrower after exposure to narrow bodies. The
      most normal looking body changed significantly after exposure to wide bodies, but
      the most attractive body did not. These results show that perceptions of body
      attractiveness can be influenced by experience, but that there is an asymmetry
      between the effects of exposure to narrow and wide bodies. We consider a possible
      mechanism for this unexpected asymmetry, as well as possible implications for the
      effects of media exposure on body-image. The most attractive body shape was
      consistently narrower than the most normal looking body shape. Substantial
      changes in what looked normal were accompanied by congruent changes in what
      looked attractive, suggesting that a normal or average body shape may function as
      a reference point against which body attractiveness is judged.

PMID- 15969828
TI  - Relationships between risk-taking behaviour and subsequent risk perceptions.
AB  - Research has suggested that engagement in patterns of risk-taking behaviour might
      have a negative influence on the processing of risk information. However, risk
      takers display higher risk perceptions than non-risk takers. This paradox might
      be resolved by removing the confounding effect of risk takers' increased exposure
      to risk. A longitudinal survey was administered to 255 motorists to examine the
      extent to which Time 1 (T1) self-reported speeding behaviour predicted exposure
      free measures of Time 2 (T2) risk perceptions. Hierarchical regression analyses,
      controlling for demographics and T1 risk perceptions, showed that T1 speeding,
      and T1 to T2 speeding changes, both inversely predicted T2 risk perceptions. This
      suggests that successive increments in risk-taking behaviour will lead to
      progressively lower increases in personal risk perception. Possible foundations
      and implications of this effect are discussed.

PMID- 15969829
TI  - Testing alleged mediumship: methods and results.
AB  - Mediums claim to be able to communicate with the deceased. Such claims attract a
      considerable amount of public interest and, if valid, have important implications
      for many areas of psychology. For over 100 years, researchers have tested alleged
      mediums. This work has obtained mixed results and provoked a considerable amount
      of methodological debate. This paper reviews the key issues in this debate,
      describes how the authors devised a method of testing that aimed to prevent the
      many problems that have hindered past research, and how they then used this
      method to test several professional mediums. The results of this work did not
      support the existence of genuine mediumistic ability. Competing interpretations
      of these results are discussed, along with ways in which the methodology
      presented in the paper could be used to assess conceptually similar, but non
      paranormal, claims made in clinical, occupational and forensic contexts.

PMID- 15969830
TI  - The effects of adult guidance and peer discussion on the development of
      children's representations: evidence from the training of pedestrian skills.
AB  - It was hypothesized that practical training is effective in improving children's
      pedestrian skills because adult scaffolding and peer discussion during training
      specifically promote E3 level representation (linguistically-encoded,
      experientially-grounded, generalizable knowledge), as defined by Karmiloff
      Smith's (1992) representational redescription (RR) model. Two studies were
      conducted to examine in detail the impact of this social input in the context of
      simulation-based training in roadside search skills. A group of 5-8-year-olds
      were pre-tested on ability to detect relevant road-crossing features. They then
      participated in four training sessions designed to promote attunement to these,
      under peer discussion versus adult guidance conditions (Study 1), and adult-child
      versus adult-group conditions (Study 2). Performance at post-test was compared
      with that of controls who underwent no training. Study 1 found that children in
      the adult guidance condition improved significantly more than those in the peer
      discussion or control conditions, and this improvement was directly attributable
      to appropriation of E3 level representations from adult dialogue. Study 2 found
      that progress was greater still when adult scaffolding was supplemented by peer
      discussion, with E3 level representation attributable to the children's
      exploration of conflicting ideas. The implications of these findings for the RR
      model and for practical road safety education are discussed.

PMID- 15969831
TI  - Naming very familiar people: when retrieving names is faster than retrieving
      semantic biographical information.
AB  - One of the most reliable findings in the literature on person indentification is
      that semantic categorization of a face occurs more quickly than naming a face.
      Here we present two experiments in which participants are shown the faces of
      their colleagues, i.e., personally familiar people, encountered with high
      frequency. In each experiment, naming was faster than making a semantic
      classification, despite the fact that the semantic classifications were highly
      salient to the participants (Experiment 1: highest degree obtained; Experiment 2:
      nationality). The finding is consistent with models that allow or parallel access
      from faces to semantic information and to names, and demonstrates the need for
      the frequency of exposure to names to be taken into account in models of proper
      name processing e.g. Burke, Mackay, Worthley and Wade (1991).

PMID- 15969832
TI  - Self-enhancement, crash-risk optimism and the impact of safety advertisements on
      young drivers.
AB  - In Study 1, young drivers (aged between 16 and 29 years, N = 314) rated their
      driving attributes relative to their peers. They also rated their likelihood of
      being involved in a crash relative to their peers (crash-risk optimism), their
      crash history, stereotype of the young driver, and concern over another health
      issue. A self-enhancement bias was found for all items in which self/other
      comparisons were made. These items formed two major factors, perceived relative
      driving ability and perceived relative driving caution. These factors and
      perceived luck relative to peers in avoiding crashes significantly predicted
      crash-risk optimism. In Study 2, an experimental group of young drivers (N = 173)
      watched safety advertisements that showed drinking and dangerous driving
      resulting in a crash, and a control group (N = 193) watched advertisements
      showing people choosing not to drive after drinking. Each group then completed
      the self/other comparisons used in Study 1. The same factors were found, but only
      driving caution significantly predicted crash-risk optimism. The experimental
      group showed more self-enhancement on driving ability than the control group. In
      both studies, men showed substantially more self-enhancement than women about
      their driving ability. Implications for safety interventions are discussed.

PMID- 15969833
TI  - Source-monitoring accuracy across repeated tests following directed forgetting.
AB  - The repeated recall of items from lists that participants were earlier instructed
      to either remember or to forget was examined in two experiments. RR participants
      (those instructed to remember both lists they were presented) tended to recall
      more List 1 items than FR participants (those instructed to forget the first list
      and to remember the second list). FR participants recalled more List 2 items than
      did RR participants, but only when directed to report those items (Experiment 1),
      not when directed to report items from both lists (Experiment 2). Participants
      experienced difficulty correctly reporting the list source of items they recalled
      and incorrect source recall increased across tests, showing hypermnesia. This
      later result underscores the need for caution when assessing the accuracy of
      information retrieved from multiple sources across repeated tests. Together, the
      data patterns provide support for the retrieval dynamics account of hypermnesia,
      the context-change account of directed forgetting, and limited support for the
      retrieval inhibition view of directed forgetting.

PMID- 15969834
TI  - Signal regularity and the mindlessness model of vigilance.
AB  - Robertson, Manly, Andrade, Baddeley, and Yiend (1997) have proposed that
      detection failures in vigilance tasks result from a 'mindless' withdrawal of
      attentional effort from the monitoring assignment. To explore that view, they
      modified the traditional vigilance task, in which observers make button-press
      responses to signify the detection of rarely occurring critical signals, to one
      in which button-press responses acknowledge frequently occurring non-signal
      events and response withholding signifies signal detection. This modification is
      designed to promote a mindless withdrawal of attentional effort from the task
      through routinization. The present study challenges the validity of the
      mindlessness model by showing that with both types of task, observers utilize
      subtle patterns in the temporal structure of critical signal appearances to
      develop expectations about the time course of those appearances that affect
      performance efficiency. Such expectations enhance performance on the traditional
      vigilance task, but degrade performance on the modified task.

PMID- 15969835
TI  - Modelling non-ignorable missing-data mechanisms with item response theory models.
AB  - A model-based procedure for assessing the extent to which missing data can be
      ignored and handling non-ignorable missing data is presented. The procedure is
      based on item response theory modelling. As an example, the approach is worked
      out in detail in conjunction with item response data modelled using the partial
      credit and generalized partial credit models. Simulation studies are carried out
      to assess the extent to which the bias caused by ignoring the missing-data
      mechanism can be reduced. Finally, the feasibility of the procedure is
      demonstrated using data from a study to calibrate a medical disability scale.

PMID- 15969836
TI  - Fitting the factor analysis model in lI norm.
AB  - The well-known problem of fitting the exploratory factor analysis model is
      reconsidered where the usual least squares goodness-of-fit function is replaced
      by a more resistant discrepancy measure, based on a smooth approximation of the
      lI norm. Fitting the factor analysis model to the sample correlation matrix is a
      complex matrix optimization problem which requires the structure preservation of
      the unknown parameters (e.g. positive definiteness). The projected gradient
      approach is a natural way of solving such data matching problems as especially
      designed to follow the geometry of the model parameters. Two reparameterizations
      of the factor analysis model are considered. The approach leads to globally
      convergent procedures for simultaneous estimation of the factor analysis matrix
      parameters. Numerical examples illustrate the algorithms and factor analysis
      solutions.

PMID- 15969837
TI  - An affine invariant rank-based method for comparing dependent groups.
AB  - A basic property of various rank-based hypothesis testing methods is that they
      are invariant under a linear transformation of the data. For multivariate data, a
      generalization of this property is sometimes sought (called affine invariance),
      but typically techniques for assigning ranks do not achieve this goal, or it is
      assumed that sampling is from a symmetric distribution. A rank-based method is
      suggested for comparing dependent groups that is based on halfspace depth, is
      affine invariant in terms of difference scores, and allows sampling from
      asymmetric distributions.

PMID- 15969838
TI  - The mean and variance of the selection differential after top-down selection from
      a mixture of normal samples.
AB  - A procedure is presented for determining the mean and variance of the selection
      differential for top-down selections in which the candidates come from
      populations that have a different average score on the selection measure.
      Although the procedure is based on the same stochastic model and requires
      identical data to the currently available method for estimating the mean
      selection differential, it has the advantage that the resulting expressions are
      valid for finite-sample selection decisions and that the variance of the
      selection differential can also be assessed. The difference between the two
      procedures is illustrated by means of an example application, and it is shown how
      the present results are particularly helpful in determining the expected utility
      of personnel selection decisions.

PMID- 15969839
TI  - Estimating population or group sensitivity and its precision from a set of
      individual d'.
AB  - A commonly used method of estimating population sensitivity is the so-called
      averaged d' method. In this method, the arithmetic mean of a set of individual d'
      is usually taken as a population sensitivity estimator. This practice ignores the
      fact that the individual d' itself is an estimator with an inherent variance. For
      observations with different levels of precision, the arithmetic mean is not the
      best estimator of a population parameter. It may lead to an estimate with a large
      variation. Another fact, which is often ignored, is that the variance of
      individual d' involves both between- and within-subject variations in a random
      effects model when population sensitivity and its level of precision are
      estimated. Failing to account for both components of variance leads to an
      underestimate of variation and an overestimate of precision for the estimator. In
      this paper a lognormal distribution rather than a normal distribution is assumed
      for individual sensitivity. An iterative weighting procedure is proposed for
      estimating population sensitivity on the log scale on the basis of a random
      effects model. An ordinary weighting procedure is proposed for estimating group
      sensitivity on the log scale on the basis of a fixed effects model. The levels of
      precision of population and group sensitivity estimators are also given.
      Numerical examples illustrate the estimation procedures.

PMID- 15969840
TI  - Examining change in maximal reliability for multiple-component measuring
      instruments.
AB  - A method for examining change in maximal reliability for pre-specified sets of
      congeneric measures when developing a multi-component instrument is outlined. The
      approach is applicable for purposes of estimation and testing of gain or loss in
      the maximal reliability coefficient as a consequence of adding or dropping one or
      more measures from a homogeneous composite with uncorrelated errors, as well as
      when one is concerned with optimal component choice for highest increase or
      correspondingly smallest drop in maximal reliability. The method is compared with
      a procedure for ascertaining change in unweighted sum score reliability, and
      implications for instrument construction and revision are discussed. The approach
      is illustrated with a numerical example.

PMID- 15969841
TI  - Multidimensional scale types and invariant multivariate statistics.
AB  - This paper proposes an extension of the definition of one-dimensional ordinal,
      interval, ratio, difference and absolute scales to the multidimensional case. The
      connection between measurement structures and statistical structures suggested in
      a previous paper is also extended to the multivariate case, and examples of
      invariance properties of multivariate functions and statistics are discussed.

PMID- 15969842
TI  - A statistical model for binocular rivalry.
AB  - A probabilistic model is presented for the phase durations in binocular rivalry
      experiments. The hypothetical construct of inhibition or reaction inhibition is
      used to account for the length of the successive phases of left-eye dominance and
      right-eye dominance. In accordance with Hull's Postulate X.B. it is assumed that
      the inhibition increases linearly at rate a1 during periods of left-eye dominance
      and decreases linearly at rate a0 during periods of right-eye dominance. Two
      different versions of the proposed model are presented: the beta and the Bessel
      inhibition models. Inhibition fluctuates between the boundaries 0 and 1 in the
      beta inhibition model and between -infinity and +infinity in the Bessel
      inhibition model. The transition rates lambda1(t) for switches from a state of
      left-eye dominance to a state of right-eye dominance, and lambda0(t) for switches
      from a state of right-eye dominance to a state of left-eye dominance depend on
      inhibition: lambda1(t)=l1 (Y(t)), lambda0(t)=l0(Y(t)), where l1 is a non
      decreasing function and l0 is a non-increasing function. In the beta inhibition
      model l1(y)=c1/(1 - y) and l0(y)=c0/y. In the Bessel inhibition model
      l1(y)=u1e(y) and l0(y)=u0/e(y). Special attention is given to the derivation of
      the expectation of the stationary phase durations.

PMID- 15969843
TI  - Latent variable models for partially ordered responses and trajectory analysis of
      anger-related feelings.
AB  - A general framework is presented for the analysis of partially ordered set
      (poset) data. The work is motivated by the need to analyse poset data such as
      multi-componential responses in psychological measurement and partially
      accomplished cognitive tasks in educational measurement. It is shown how the
      generalized loglinear model can be used to represent poset data that form a
      lattice and how latent-variable models can be constructed by further specifying
      the canonical parameters of the loglinear representation. The approach
      generalizes a class of latent-variable models for completely ordered data. We
      apply the methods to analyse data on the frequency and intensity of anger-related
      feelings. Furthermore, we propose a trajectory analysis to gain insight into the
      response function of partially ordered emotional states.

PMID- 15969844
TI  - Multilevel IRT using dichotomous and polytomous response data.
AB  - A structural multilevel model is presented where some of the variables cannot be
      observed directly but are measured using tests or questionnaires. Observed
      dichotomous or ordinal polytomous response data serve to measure the latent
      variables using an item response theory model. The latent variables can be
      defined at any level of the multilevel model. A Bayesian procedure Markov chain
      Monte Carlo (MCMC), to estimate all parameters simultaneously is presented. It is
      shown that certain model checks and model comparisons can be done using the MCMC
      output. The techniques are illustrated using a simulation study and an
      application involving students' achievements on a mathematics test and test
      results regarding management characteristics of teachers and principles.

PMID- 15969845
TI  - A method for testing group differences of scale validity in multiple population
      studies.
AB  - A method for testing equality in validity of multi-component measuring
      instruments across populations is outlined. The approach is developed within the
      framework of covariance structure modelling and complements earlier research on
      examining group differences in scale reliability. The procedure is particularly
      useful for purposes of ascertaining comparability of validity when constructing
      and developing measuring instruments. The method also provides ranges of
      plausible values for differences in composite validity across several populations
      and allows one to evaluate group discrepancies in validity of behavioural scales.
      The approach is illustrated using data from a cognitive intervention study.

PMID- 15969847
TI  - Childhood IQ and all-cause mortality before and after age 65: prospective
      observational study linking the Scottish Mental Survey 1932 and the Midspan
      studies.
AB  - OBJECTIVES: The objective was to investigate how childhood IQ related to all
      cause mortality before and after age 65. DESIGN: The Midspan prospective cohort
      studies, followed-up for mortality for 25 years, were linked to individuals'
      childhood IQ from the Scottish Mental Survey 1932. METHODS: The Midspan studies
      collected data on risk factors for cardiorespiratory disease from a questionnaire
      and at a screening examination, and were conducted on adults in Scotland in the
      1970s. An age 11 IQ from the Scottish Mental Survey 1932, a cognitive ability
      test conducted on 1921-born children attending schools in Scotland, was found for
      938 Midspan participants. The relationship between childhood IQ and mortality
      risk, adjusting for adulthood socio-economic confounders, was analysed. The
      effect of adjustment for childhood IQ on the relationship between established
      risk factors (blood pressure, smoking, height and respiratory function) and
      mortality was also investigated. RESULTS: For deaths occurring up to age 65,
      there was a 36% increased risk per standard deviation decrease (15 points) in
      childhood IQ which was reduced to 29% after adjusting for social class and
      deprivation category. There was no statistically significant relationship between
      childhood IQ and deaths occurring after the age of 65. Adjustment for childhood
      IQ attenuated the risk factor-mortality relationship in deaths occurring up to
      age 65, but had no effect in deaths occurring after age 65. CONCLUSIONS:
      Childhood IQ was significantly related to deaths occurring up to age 65, but not
      to deaths occurring after age 65.

PMID- 15969848
TI  - Causal beliefs and behaviour change post-myocardial infarction: how are they
      related?
AB  - INTRODUCTION: Weinman, Petrie, Sharpe, and Walker (2000) showed that the causal
      attributions of a sample of first-time myocardial infarction (MI) patients and
      their spouses from Auckland, New Zealand, were associated with changes in health
      related behaviour over the first 6 months post-MI. However, their analyses did
      not control for pre-MI health-related behaviour. METHOD: This paper reports a re
      analyses of the Auckland data, and a replication study conducted with 155 first
      time MI patients in Brighton, United Kingdom (UK), to investigate whether
      baseline attributions for MI were related to health-related behaviour change at 6
      months (N=132). Spouses (N=85) also completed the attribution questionnaire at
      baseline. RESULTS: There was no consistent relationship between the causal
      attributions of patients and subsequent behaviour change in Auckland and
      Brighton. For both samples, causal attributions were associated with pre-MI
      behaviour. CONCLUSIONS: The data from both samples suggest that the causal
      attributions of MI patients and their spouses may be realistic, but not
      predictive of subsequent changes in behaviour.

PMID- 15969849
TI  - 'Nobody likes damaged goods': the experience of adult visible acne.
AB  - OBJECTIVES: While mild to severe acne is a common problem in the teenage years,
      many adults also suffer from the condition. Although there is an appreciable body
      of dermatological literature on this issue, the psychosocial concomitants of
      severe, visible adult acne are little elaborated. The aim of this research is to
      detail the salient experiences of adults with severe visible acne, and to set out
      the implications of these experiences. DESIGN: A phenomenological qualitative
      approach was adopted to elicit detailed accounts of the impact of visible acne
      upon the lives of a small sample of sufferers. METHOD: 11 adults suffering from
      severe visible acne took part in semi-structured interviews via e-mail, over an
      extended period of time. Transcripts of these interviews served as the data for
      an interpretative phenomenological analysis. RESULTS: Five themes emerged,
      detailing different aspects of respondents' personal and social lives in the
      context of their acne. These were: powerlessness and the variable nature of acne;
      comparisons, self-image and identity; the experience of general social
      interaction; relationships with family and friends; and gender, sexuality, and
      romantic relationships. CONCLUSIONS: These themes allowed a deeper understanding
      of issues reported in previous quantitative research in the area, as well as
      revealing findings that had not been previously reported in relation to the
      experience of adult acne and its impact upon personal and social relationships.
      With an acknowledgement of these experiences, personal and professional
      acquaintances have the potential to improve their interpersonal relationship with
      the person concerned, and encourage positive changes in their psychological
      health and social interaction.

PMID- 15969850
TI  - Can safer-sex promotion leaflets change cognitive antecedents of condom use? An
      experimental evaluation.
AB  - An experimental evaluation of a safer sex promotion leaflet was undertaken to
      assess its capacity to change antecedent cognitions of condom use. The leaflet
      was identified in a previous study as addressing research-based cognitive
      antecedents of condom use. A pre-post-test experimental study including three
      conditions was conducted: (a) presentation of the leaflet; (b) presentation of
      the leaflet plus incentive for systematic processing; (c) no-leaflet control. The
      leaflet was evaluated in terms of its capacity to change eight cognitive
      correlates of condom use identified in a recent meta-analysis. The sample
      consisted of 230 tenth-grade students. Following baseline assessments, leaflet
      induced change was measured immediately following the intervention and at a
      follow up 4 weeks post-intervention. The target leaflet alone did not result in
      significant changes in the cognitive antecedents of condom use compared with the
      control condition. However, in combination with an incentive for systematic
      processing, the target leaflet had a greater impact on cognitive antecedents than
      the no-leaflet control condition. The findings are discussed with regard to the
      development and evaluation of research-based health-promotion materials.

PMID- 15969851
TI  - Discontinuity patterns in stages of the precaution adoption process model: meat
      consumption during a livestock epidemic.
AB  - OBJECTIVES: Patterns of changes in social-cognitive variables were investigated
      in order to test selected stages of the precaution adoption process model (PAPM).
      It was hypothesized that non-linear trends (discontinuity patterns) in perceived
      vulnerability, positive and negative outcome expectancies, procrastination, and
      self-efficacy might be observed across the stages. DESIGN: Cross-sectional data
      from 808 respondents were employed. METHOD: Questionnaire data were collected in
      an on-line study on meat consumption during a livestock epidemic in Germany.
      Polynomial trends and analyses of variance with post-hoc-contrasts were used to
      examine the patterns of change. RESULTS: Discontinuity patterns were found for
      perceived vulnerability, negative outcome expectancies, and procrastination. The
      data provided partial support for discontinuity patterns in self-efficacy.
      Continuity patterns were found for positive outcome expectancies. CONCLUSIONS:
      Results provide support for a stage model rather than a pseudo-stage model.

PMID- 15969852
TI  - Emergency contraception use and non-use in young women: the application of a
      contextual and dynamic model.
AB  - There have been many approaches to understanding contraception use including
      social cognition models which have been criticised for their individualistic
      approach and their static nature. The present quantitative study developed and
      refined a contextual and dynamic model of contraception use that was derived
      using qualitative research. This model conceptualizes the predictors of
      contraception use in terms of the meaning and importance of a range of social
      goals, perceptions of vulnerability, and constraints on or facilitators of
      contraception use each of which changes over time. The present study
      operationalized this model in relation to emergency contraception and explored
      differences between users and non-users and between episodes of use and non-use.
      In terms of users and non-users, the results showed that the users of emergency
      contraception showed a more positive view of an emergency contraception user,
      perceived greater support from their partner for emergency contraception use,
      rated themselves more at risk of pregnancy, and felt more confident about asking
      for emergency contraception. In terms of use and non-use, use was related to an
      increased belief about the risk of pregnancy, increased partner support,
      increased concern about health care professionals and the side-effects of the
      drug, and a more positive identity of an emergency contraception. The study has
      helped to develop and refine the model and has identified some key factors that
      are specifically relevant to emergency contraception use in a sample of women in
      education in and around London.

PMID- 15969853
TI  - Substance use among pregnant women in the context of previous reproductive loss
      and desire for current pregnancy.
AB  - OBJECTIVE: The primary objectives of this study were to explore maternal history
      of perinatal loss and pregnancy wantedness as correlates of substance use during
      pregnancy. METHOD: The research design involved interviewing women who gave birth
      in Washington DC hospitals during 1992. Interview data included pregnancy history
      (prior births, induced abortions, miscarriages, and stillbirths), desire for the
      pregnancy (wanted, not wanted, mistimed), socio-demographic information, timing
      of onset of prenatal care, and substance use (cigarettes, alcohol, and drugs)
      during pregnancy. RESULTS: A history of induced abortion was associated with
      elevated risk for maternal substance use of various forms; whereas other forms of
      perinatal loss (miscarriage and stillbirth) were not related to substance use.
      Unwanted pregnancy was associated with cigarette smoking during pregnancy, but
      not with any other forms of substance use. CONCLUSIONS: Reproductive history
      information may offer insight to professionals pertaining to the likelihood of
      women using substances in a later pregnancy.

PMID- 15969854
TI  - Stress, oral health behaviour and clinical outcome.
AB  - OBJECTIVE: Several studies indicate that stress adversely affects various health
      behaviours. Oral hygiene behaviour, however, has been rarely studied in this
      context. The present study thus aims to assess the effects of stress on oral
      hygiene behaviour and clinical outcome. DESIGN: In a prospective matched
      controlled design 12 pairs of medical students, each consisting of 1 student
      participating in a major academic exam and 1 student not participating in any
      exams (control) were studied. METHODS: A professional tooth cleaning was
      performed 4 weeks prior to exams to obtain plaque levels of 0 at all sites.
      Immediately prior to professional tooth cleaning and 4 weeks after exams plaque
      levels (as indicator of oral hygiene behaviour) and bleeding on probing (an
      indicator of gingivitis) were assessed. RESULTS: No group differences were
      observed at the beginning of the exam period; after exams significant higher
      rates of plaque (p=.0005, d=1.74) and gingivitis (p=.016, d=1.01) were observed
      in exam students as compared with controls. CONCLUSIONS: The study illustrates
      the clinical significance of stress effects on health behaviour. Stress should be
      included as a factor in models of patient compliance and health behaviour.

PMID- 15969855
TI  - The DAS24: a short form of the Derriford Appearance Scale DAS59 to measure
      individual responses to living with problems of appearance.
AB  - OBJECTIVES: To develop a psychometrically robust and widely applicable short form
      of the Derriford Appearance Scale, (DAS59), which (1) will reliably and validly
      assess the distress and difficulties experienced in living with problems of
      appearance, (2) is acceptable to clinical and non-clinical populations, and (3)
      facilitates research and clinical decision-making through good standardization
      and sensitivity. DESIGN: Cross-sectional survey designs using clinical (out
      patient and in-patient) and general population samples. METHOD: Twenty-five items
      were selected initially from the 59 items of the original DAS59. These were
      refined to 24 through item analyses and the scale was standardized on 535
      patients with a range of problems of appearance and on a representative general
      population sample (N=1, 107). RESULTS: All 24 items contributed well to the total
      score and internal consistency was high (alpha=.92). Test-retest reliability (6
      months) was good (0.82), and criterion validity, with the DAS59, was excellent
      (0.88). Good construct validity was demonstrated in differences between (1)
      patient and general population samples, (2) members of the general population
      concerned and not concerned about their appearance, and (3) in patterns of
      convergent and divergent correlations with a range of established scales. The
      general population data revealed widespread concerns about appearance.
      CONCLUSION: The DAS24 provides a widely applicable and acceptable short form of
      the original DAS59. It is psychometrically robust and discriminates well between
      patient groups, between clinical and non-clinical populations, and within the
      general population between those concerned, and those not concerned, about their
      appearance.

PMID- 15969856
TI  - The role of pre-operative state-anxiety in the determination of intra-operative
      neuroendocrine responses and recovery.
AB  - OBJECTIVES: The psychophysiological model of adjustment to surgery predicts
      associations between (1) heightened pre-operative state-anxiety and intra
      operative neuroendocrine responses, (2) neuroendocrine responses and
      complications; and (3) heightened pre-operative state-anxiety and post-operative
      recovery. The present study examined these associations. METHODS: Participants
      were 39 patients (mean age 71.9+/-6.1 years) undergoing elective carotid
      endarterectomy surgery under local anaesthesia. In the week prior to surgery,
      patients completed baseline measures of physical and mental functioning using the
      MOS 36-item Short-Form Health Survey (SF-36). In addition to this, they undertook
      a 24-hour urine save to measure cortisol and catecholamines. Measures of state
      anxiety were completed on the evening prior to surgery. A second 24-hour urine
      save was started at the time of anaesthetic induction. Follow-up measures of
      physical and mental functioning were completed 1 month following surgery. All
      complications were recorded during hospitalization. RESULTS: There was a
      significant negative association between pre-operative state-anxiety and intra
      operative cortisol (r=-.52, p<or=.001). Using hierarchical regression analysis,
      pre-operative state-anxiety accounted for 10% of the variance in intra-operative
      cortisol responses after controlling for medical and demographic factors. There
      were no significant associations between neuroendocrine responses and
      complications. Pre-operative state-anxiety was a significant determinant of
      poorer mental functioning following surgery, explaining 10% of the variance in
      scores after adjusting for baseline mental functioning. CONCLUSIONS: Results from
      this study show increasing pre-operative anxiety to be associated with lower
      intra-operative cortisol responses and poorer mental functioning 1 month
      following surgery.

PMID- 15969857
TI  - Epoetin alfa (Eprex) and quality of life.
AB  - Several recently published clinical trials in anaemic patients with cancer
      provide convincing evidence that the quality of life of such patients is
      considerably impaired and that a significant improvement in quality of life can
      be achieved if their anaemia is corrected by treatment with recombinant
      erythropoietin (epoetin alfa, Eprex). Findings of some of the major studies are
      summarised in this issue. These summaries have been prepared to make the findings
      more accessible to busy clinicians who may not have time to read longer reports
      in specialist journals but who need to understand the important clinical
      implications of this research.

PMID- 15969858
TI  - Improvements in quality of life associated with epoetin alfa treatment are
      clinically, as well as statistically, significant.
AB  - Fatigue can be a major problem for cancer patients receiving chemotherapy, and
      anaemia is known to be an important contributory factor. Several studies have
      shown that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue
      and improves health-related quality of life (HrQoL). However, it is often
      difficult for clinicians to relate reported HrQoL improvements from clinical
      trials to meaningful benefits for their patients. Results from a large-scale,
      placebo-controlled study were used to determine the minimally important
      difference in HrQoL, defined as the 'smallest difference in score...which
      patients perceive as beneficial and which would mandate...a change in the
      patient's management'. This analysis confirmed that, for the five QoL scales
      used, epoetin alfa conferred not only a statistically significant but also a
      clinically significant benefit in terms of QoL compared to placebo, since, in
      each case, the benefit associated with epoetin alfa use was considerably higher
      than the minimally important difference.

PMID- 15969859
TI  - Benefits of epoetin alfa for cancer patients' quality of life are confirmed after
      modelling to account for missing data.
AB  - Incomplete data are inevitable in quality-of-life (QoL) studies involving cancer
      patients, since a proportion of patients will not complete the trial. Traditional
      analyses assume that such data are missing at random, but this assumption may be
      incorrect. We therefore applied mixed-effects statistical models to determine the
      effects of non-random missing data. Models were applied to results from a large
      scale, randomised study of epoetin alfa versus placebo in 375 patients receiving
      non-platinum-based chemotherapy. The model suggested that QoL data were not
      missing at random and that analyses based on an assumption of random missing data
      gave an over-optimistic impression of QoL changes within treatment groups.
      However, sensitivity analysis demonstrated that the effectiveness of treatment
      with epoetin alfa compared to placebo in terms of QoL benefits remained highly
      significant, confirming the original conclusions of the study.

PMID- 15969860
TI  - Treating anaemia with epoetin alfa is associated with improvements in quality of
      life in cancer patients receiving chemotherapy.
AB  - Anaemia is an important factor in the fatigue experienced by many patients
      receiving chemotherapy. A recent large-scale, randomised, placebo-controlled
      trial has shown that treatment with epoetin alfa raises haemoglobin levels,
      reduces fatigue and improves overall quality of life (QoL). In order to examine
      the relationship between anaemia and QoL more closely, we performed multiple
      regression analyses, adjusting for possible differences in demographic and
      clinical characteristics between the treatment groups on the trial data derived
      from FACT, CLAS and SF-36 QoL assessments. This confirmed that QoL is correlated
      with haemoglobin levels and that treatment with epoetin alfa is associated with a
      significant improvement in QoL as measured by validated cancer-specific
      instruments such as FACT and CLAS. However, the sub-group of patients who suffer
      disease progression during treatment are not predicted to experience an
      improvement in QoL, confirming the sensitivity of these scales. Race and tumour
      type were significantly related to changes in QoL scores, but other factors such
      as age and gender did not show significant effects on QoL.

PMID- 15969861
TI  - Epoetin alfa offers clinically significant improvements in the quality of life of
      anaemic cancer patients.
AB  - Anaemia is a common problem for cancer patients and often causes fatigue and
      reduces quality of life (QoL). Although randomised trials have repeatedly shown
      that treatment with epoetin alfa raises haemoglobin levels, reduces fatigue and
      improves overall QoL, such findings may be hard to put into a clinical context
      and, as a result, cancer-related fatigue remains undertreated. This study
      gathered data using the FACT-An QoL scale from 1400 people on an internet survey
      panel. The 1400 were randomly selected and chosen to be representative of the
      total US population. Survey results were then compared with the findings from a
      large placebo-controlled study involving 375 anaemic cancer patients. FACT-An
      showed good psychometric properties in the survey population and was able to
      distinguish respondents with histories of anaemia and cancer from those without.
      Comparing the population norm values for FACT-An with the trial data showed that
      treatment with epoetin alfa led to clinically meaningful improvements in cancer
      patients' QoL.

PMID- 15969862
TI  - Meta-analysis of the effects of epoetin alfa treatment on quality of life in
      anaemic cancer patients.
AB  - Treatment with epoetin alfa has repeatedly been shown to improve the quality of
      life (QoL) of cancer patients with anaemia. We used meta-analytical techniques to
      synthesise data from all available (published and unpublished) studies of epoetin
      alfa in cancer patients receiving chemotherapy that used validated QoL
      instruments. Results from 23 studies were synthesised. These employed the CLAS,
      FACT, SF-36 and ECOG (WHO) QoL scales. The meta-analysis indicated that treatment
      with epoetin alfa was associated with a clear and statistically significant
      improvement in QoL as measured by all subscales of CLAS, all subscales of FACT,
      and 5 subscales of SF-36. In contrast, control groups experienced no significant
      change, or, in some cases, a deterioration in QoL. Improvement was related to
      treatment duration. The generic ECOG (WHO) performance scale indicated that, even
      though epoetin alfa treatment is associated with clear benefits in terms of QoL,
      this population of patients receiving chemotherapy for cancer experience a
      gradual decrease in functional status over time.

PMID- 15969863
TI  - Pre-treatment erythropoietin levels cannot be used to predict individual response
      to epoetin alfa in anaemic cancer patients.
AB  - Recombinant human erythropoietin (epoetin alfa) is an effective treatment for
      anaemia in cancer patients, and over two-thirds of recipients experience a
      substantial increase in haemoglobin concentration (>2 g/dl). However, it would be
      helpful to identify responders before starting treatment. Some studies have
      suggested that high pre-treatment levels of endogenous erythropoietin pre
      treatment levels of endogenous erythropoietin or other pre-treatment or early
      response variables are associated with a poor response to epoetin alfa, and
      several predictive algorithms have been published. We analysed data pooled from 9
      clinical trials of 1010 patients to determine the clinical usefulness of pre
      treatment erythropoietin levels and other variables for predicting response. This
      showed that pre-treatment factors alone do not provide a clinically useful
      prediction of response. The sensitivity of these models increases slightly if
      early response variables, such as the change in haemoglobin after 4 weeks, are
      included, but specificity remains poor. We conclude that, while there may be a
      statistical relationship between certain factors and response, none approach
      clinically useful levels of sensitivity or specificity.

PMID- 15969864
TI  - Imipenem/cilastatin versus piperacillin/tazobactam plus amikacin for empirical
      therapy in febrile neutropenic patients: results of the COSTINE study.
AB  - BACKGROUND: Combinations of beta-lactams plus aminoglycosides have become
      standard therapy for suspected infections in patients with profound neutropenia.
      However, it is not clear whether such combinations are advantageous over therapy
      with a broad-spectrum antibiotic. OBJECTIVE: To assess the clinical effectiveness
      and the cost-effectiveness ratio of empirical therapy of febrile neutropenia with
      imipenem/cilastatin (I/C) versus piperacillin/tazobactam plus amikacin (P/T+A).
      RESEARCH DESIGN AND METHODS: Prospective, multicenter observational study with 2
      matched parallel cohorts treated with I/C (500 mg/6 h iv) or P/T+A (P/T: 4 g/6 h
      iv; A: 20 mg/kg/day iv). MAIN OUTCOME MEASURES: Therapeutic success was defined
      as the resolution of fever following > or = 7 days of unchanged antibiotic
      treatment. An economic comparison was conducted focusing on the daily treatment
      costs, and the management of its toxicity. RESULTS: There were 343 eligible
      patients (180 I/C, 163 P/T+A), of whom 290 were evaluable for the primary
      clinical effectiveness analysis. Follow-up information beyond 7 days of study
      inclusion was only available for 52% of all evaluable patients. Treatment success
      was observed in 42% of I/C patients compared with 31% of P/T+A patients (95% CI: 
      0.01, 21.4). The incidence of drug-related adverse experiences was 13% for I/C
      and 6% for P/T+A, with no differences in moderate or severe adverse experiences
      nor in those causing discontinuation of antibiotic therapy. Treatment costs were
      189.55 euros (95% CI: 127.46-251.46) lower per episode of febrile neutropenia for
      patients treated with I/C. CONCLUSIONS: The clinical effectiveness of I/C was
      similar to that of P/T+A. In both treatment groups toxicity was low and did not
      limit antibiotic therapy. Resource consumption was lower with I/C.

PMID- 15969865
TI  - A long-term, open-label extension study on the safety of treatment with lanthanum
      carbonate, a new phosphate binder, in patients receiving hemodialysis.
AB  - BACKGROUND: Lanthanum carbonate, a new phosphate binder, is effective in reducing
      serum phosphorus levels in patients with end-stage renal disease. A 1-year
      extension study to two randomized controlled studies was conducted to evaluate
      the long-term safety of lanthanum carbonate in patients who received
      hemodialysis. RESEARCH DESIGN AND METHODS: Patients from two previous lanthanum
      carbonate studies were eligible to continue treatment in a 1-year open-label
      extension. A total of 77 patients (N = 77; 11 from Study 1, 66 from Study 2) were
      enrolled in this extension. The mean age of patients was 60.9 years (SD +/- 12.5
      years); 65% were male and 35% were female. All patients received lanthanum
      carbonate at the optimal dose for phosphorus control, determined in their
      previous study. Safety and tolerability were assessed by monitoring adverse
      events, laboratory parameters, and vital signs. The number of patients who
      maintained serum phosphorus levels at < or = 5.9 mg/dL (1.9 mmol/L) was recorded,
      along with serum calcium, calcium x phosphorus product, and parathyroid hormone
      levels. RESULTS: Lanthanum carbonate was well tolerated and was associated with
      few treatment-related adverse events. The most commonly reported adverse events
      were nausea (26.0%), peripheral edema (23.4%), and myalgia (20.8%). No treatment
      related serious adverse events occurred. By Week 4, the mean serum phosphorus
      level had decreased by approximately 1 mg/dL to 5.7 +/- 2.0 mg/dL (1.84 +/- 0.7
      mmol/L). At the end of the study, the mean pre-dialysis serum phosphorus level
      was 5.7 +/- 1.4 mg/dL (1.84 +/- 0.5 mmol/L); 53% of patients had controlled
      phosphorus levels. Calcium x phosphorus product decreased during Week 1 and
      remained within a clinically acceptable range thereafter. There were no
      clinically significant changes in serum calcium, or parathyroid hormone levels.
      CONCLUSION: Lanthanum carbonate is well tolerated and is effective for the long
      term maintenance of serum phosphorus control in patients with end-stage renal
      disease.

PMID- 15969866
TI  - Nicotinic acid in the management of dyslipidaemia associated with diabetes and
      metabolic syndrome: a position paper developed by a European Consensus Panel.
AB  - Individuals with type 2 diabetes and metabolic syndrome are at markedly increased
      risk of cardiovascular morbidity and mortality. The increasing prevalence of both
      conditions poses a major challenge for clinicians in the 21st century. Both
      diabetes and metabolic syndrome are associated with a clustering of
      cardiovascular risk factors. In particular, dyslipidaemia characterised by low
      plasma levels of high-density lipoprotein cholesterol (HDL-C), elevated
      triglycerides and an increase in small, dense low-density lipoprotein (LDL)
      particles (the lipid triad), has been established as the most important
      modifiable risk factor for coronary heart disease (CHD). Current treatment
      guidelines recognise the increased CHD risk associated with diabetes and
      metabolic syndrome and focus on LDL-C lowering with statin treatment, in addition
      to dietary and lifestyle modification, as the primary lipid-modifying therapy.
      However, while there is no doubt that statin therapy significantly reduces CHD
      risk in these patients, their residual absolute risk remains higher than in
      individuals without diabetes or metabolic syndrome. Thus, there is a clear need
      to target other aspects of lipoprotein metabolism, notably low HDL-C and
      hypertriglyceridaemia, to further reduce CHD risk. Combining statin therapy
      (targeting LDL-C) with interventions that also modify low HDL-C and elevated
      triglycerides could be a useful strategy to optimise CHD risk reduction. Cautious
      combination of a fibrate or nicotinic acid with a statin is useful for the
      management of combined dyslipidaemia. Nicotinic acid is the more potent agent for
      raising HDL-C (by up to 29% at clinically recommended doses). It also
      substantially reduces triglycerides and LDL-C, and promotes a shift from small,
      dense LDL to larger, more buoyant LDL particles. Preliminary clinical data
      suggest that combining nicotinic acid with a statin will produce a greater
      reduction in cardiovascular risk in patients with diabetes and metabolic syndrome
      than statin monotherapy alone. Nicotinic acid is also safe for use in patients
      with diabetes, with no evidence of clinically relevant deterioration in glycaemic
      control at recommended doses (< or = 2 g/day). On review of the available
      evidence, this European Consensus Panel recommends the combination of nicotinic
      acid and a statin, together with lifestyle modification, as a useful strategy to
      lower CHD risk in patients with diabetes and metabolic syndrome. Prolonged
      release nicotinic acid with improved tolerability compared with previous
      formulations may have obvious advantages for use in this setting.

PMID- 15969867
TI  - Effects of a new formulation of olopatadine ophthalmic solution on nasal symptoms
      relative to placebo in two studies involving subjects with allergic
      conjunctivitis or rhinoconjunctivitis.
AB  - BACKGROUND: A new formulation of olopatadine hydrochloride ophthalmic solution
      (olopatadine 0.2%) was evaluated in two separate, randomized, placebo-controlled,
      double-masked, hybrid environmental studies intended to determine efficacy and
      safety in subjects with histories of seasonal allergic conjunctivitis or
      rhinoconjunctivitis. DESIGN AND METHODS: In these 10- and 12-week trials
      (conducted April-August 2003 and July-December 2001, respectively), subjects
      assessed their ocular signs and symptoms. Additionally, subjects in the 10-week
      trial evaluated the frequency of their nasal symptoms while subjects in the 12
      week trial evaluated both the frequency and severity of their nasal symptoms. The
      two trials had a combined enrollment of 500 subjects (217 males, 283 females)
      including 44 children aged 10-17 years; the combined population was 81.4%
      Caucasian, 9.2% Black, 2% Hispanic, and 7.4% other. Daily throughout these
      studies, either ragweed (fall study) or grass (spring study) pollen counts were
      obtained from each investigative center. Slope analyses were conducted on the
      nasal symptom assessments by pollen count. RESULTS: The nasal results from the
      two clinical trials are presented herein. In the fall study, relative to placebo,
      olopatadine 0.2% significantly reduced the frequency of pollen effects on
      sneezing (p = 0.0355) and itchy nose (p = 0.0032), and reduced the severity of
      pollen effects on sneezing (p = 0.0451), itchy nose (p = 0.0178), and runny nose
      (p = 0.0327). In the spring study, olopatadine 0.2% significantly reduced the
      frequency of pollen effects on sneezing (p = 0.0017) and runny nose (p = 0.0031)
      relative to placebo. In the fall trial, 2 subjects discontinued due to treatment
      related adverse events (tachycardia and dry eye), while in the spring study, no
      subject discontinued due to a treatment-related adverse event. No subject in
      either study suffered a treatment-related serious adverse event. CONCLUSIONS: For
      the subjects enrolled in these studies, olopatadine 0.2% appeared to be safe,
      well-tolerated, and effective in significantly reducing the frequency and/or
      severity of some effects of pollen on nasal symptoms.

PMID- 15969868
TI  - Safety of the newer antiepileptic drug oxcarbazepine during pregnancy.
AB  - OBJECTIVE: Seizure control in pregnant women with epilepsy is vital, as maternal
      seizures may have deleterious consequences. The treatment of pregnant women with
      epilepsy is, however, complicated by the teratogenicity of older antiepileptic
      drugs (AEDs). In this review, the safety of the newer AED oxcarbazepine during
      pregnancy is assessed based on published pregnancy outcome data. Other relevant
      safety issues, such as oxcarbazepine pharmacokinetics during pregnancy and the
      compatibility of oxcarbazepine treatment with breastfeeding, are also discussed.
      METHODS: Literature searches of the following databases were performed: MEDLINE,
      EMBASE, eNova, NOWIMA (an internal Novartis Germany database), Derwent Drug File,
      SciSearch and BIOSIS. Identified publications were examined for original data
      reporting rates of foetal malformation following maternal exposure to
      oxcarbazepine as monotherapy or adjunctive therapy. RESULTS: Relevant
      publications reporting data from the worldwide Novartis safety database and
      pregnancy registries or study centres in six countries were identified. A total
      of 248 pregnancies involving maternal exposure to oxcarbazepine monotherapy and
      61 involving adjunctive therapy were reported. There were six malformations among
      the monotherapy group, equating to a malformation rate of 2.4% (6/248). The
      malformation rate reported in the general population is 2-4%. There were four
      malformations associated with oxcarbazepine adjunctive therapy, equating to a
      malformation rate of 6.6% (4/61). CONCLUSIONS: This literature review suggests
      that, compared with newborns in the general population, the newborns of women
      receiving oxcarbazepine monotherapy during pregnancy do not appear to show an
      increased risk for malformations. However, the number of pregnancies involving
      maternal exposure to oxcarbazepine identified by this review is not sufficient to
      draw definitive conclusions. Additional information from large-scale pregnancy
      registries is required to confirm the safety profile of oxcarbazepine as
      monotherapy or adjunctive therapy during pregnancy.

PMID- 15969869
TI  - Comments on European Medical Writers Association (EMWA) guidelines on the role of
      medical writers in developing peer-reviewed publications.

PMID- 15969870
TI  - Verteporfin therapy in combination with triamcinolone: published studies
      investigating a potential synergistic effect.
AB  - Evidence from randomized, placebo-controlled, double-masked studies has
      demonstrated that verteporfin (Visudyne) therapy is effective in reducing the
      risk of visual acuity loss in selected groups of patients with choroidal
      neovascularization (CNV) due to age-related macular degeneration (AMD). Pilot
      studies of intravitreal triamcinolone acetonide monotherapy revealed promising
      results in patients with CNV due to AMD, but the visual acuity outcomes in a
      randomized, controlled study were lower than anticipated. Recently, however,
      there has been growing interest in the adjunctive use of triamcinolone to improve
      visual acuity and reduce regrowth of CNV in patients receiving verteporfin
      therapy. This review article surveys the currently available evidence, based on a
      Medline search covering the years 1980-2005 and abstracts from recent scientific
      meetings. A number of small-scale, uncontrolled pilot studies have indicated that
      the combination of triamcinolone acetonide with verteporfin therapy may be
      beneficial. Evidence is now needed from randomized, controlled studies to
      determine whether the potential benefits of combination therapy outweigh the
      possible risks of increased intraocular pressure, endophthalmitis, and
      progression of cataract that have been observed in trials of triamcinolone
      monotherapy.

PMID- 15969871
TI  - Effect of donepezil in patients with Alzheimer's disease previously untreated or
      treated with memantine or nootropic agents in Germany: an observational study.
AB  - OBJECTIVE: This open-label, prospective, observational, Post-Marketing
      Surveillance (PMS) study assessed the efficacy and safety of donepezil in
      patients who had been switched from therapies currently used in Germany to treat
      Alzheimer's disease (AD), such as memantine and nootropics, due to insufficient
      efficacy or poor tolerability. A treatment-naive population was included as a
      comparator. RESEARCH DESIGN AND METHODS: Patients with AD were treated with
      donepezil and observed for a period of approximately 3 months. A cognitive
      assessment was made using the Mini-Mental State Examination (MMSE). Quality of
      life (QoL) was assessed by the investigators who answered the question 'How did
      therapy with donepezil influence the QoL of the patient and/or his family over
      the observation period?' and was graded using three ratings:
      improved/unchanged/worsened. Adverse events (AEs) were also monitored. RESULTS: A
      total of 913 patients entered the study (mean +/- SD MMSE score 18.03 +/- 5.34).
      Efficacy assessments were analyzed for three groups: an overall group of patients
      who had received any form of prior AD drug therapy (N+ group; n = 709); a
      subgroup of patients from the N+ group who had received prior memantine therapy
      only (M+ group; n = 111) and patients who were drug treatment naive (N- group; n
      = 204). In the evaluable population donepezil improved MMSE scores by 2.21 +/-
      3.47 points on average, with similar improvements observed in all three groups.
      QoL was judged to be improved in at least 70% of patients, again with similar
      results obtained for all three groups. Donepezil was well tolerated, with 85 of
      913 (9.3%) patients reporting AEs. The most common AEs were those typically seen
      with cholinergic therapies (i.e., diarrhoea, vomiting and nausea). CONCLUSIONS:
      In this observational PMS study, donepezil was shown to be efficacious and well
      tolerated in patients who were being insufficiently treated with memantine or
      nootropic therapy. The magnitude of response was similar to that observed in
      patients who were previously treatment naive, suggesting prior medication does
      not effect donepezil's efficacy.

PMID- 15969872
TI  - Evaluation of health status in epilepsy using the EQ-5D questionnaire: a
      prospective, observational, 6-month study of adjunctive therapy with anti
      epileptic drugs.
AB  - AIMS: The aims of this project were to evaluate the impact of adjunctive
      treatment with an anti-epileptic drug (AED) on the health status of people with
      epilepsy and to investigate how seizure frequency affects their health status.
      METHODS: Adult epilepsy patients, refractory to current treatment, were included
      in this prospective observational study. Patients commencing adjunctive therapy
      with one of five AEDs (topiramate, lamotrigine, gabapentin, clobazam, vigabatrin)
      were eligible for inclusion. The study took place at the outpatient clinics of
      the National Hospital for Neurology and Neurosurgery, Queen Square, London.
      Patients completed the EQ-5D, a generic health status measure, at baseline and
      again after 3 and 6 months. Information was also collected on medications and
      seizure frequency. RESULTS: In total, 125 patients entered the study and were
      followed up for 6 months. Patients treated with topiramate had a significant
      increase (p < 0.05) in EQ-5D score from baseline, indicating an improvement in
      their health status whereas scores for lamotrigine, clobazam and gabapentin all
      showed a non-significant decline. When the data were analysed according to
      seizure frequency, only patients who became seizure-free on adjunctive treatment
      had a significant increase in their health status. The group who had a 50%
      reduction in seizure frequency did not have increased health status. CONCLUSIONS:
      In summary, adjunctive treatment with topiramate significantly increased health
      status as measured by the EQ-5D. These data also suggest that achievement of
      seizure-freedom is the key to improving health status in this patient group.

PMID- 15969873
TI  - Needlestick injury in acute care nurses caring for patients with diabetes
      mellitus: a retrospective study.
AB  - OBJECTIVE: To quantify the incidence and assess the risk of needlestick injury
      (NI) in nurses caring for patients with diabetes mellitus. METHODS: A total of
      400 nurses caring for patients with diabetes in 381 different hospitals
      throughout the United States over a period of at least 1 year voluntarily
      completed an Internet-based data collection instrument. The nurses self-reported
      comprehensive data on their experience with NI, focusing on those occurring
      within the past year. If respondents experienced multiple NI during this period,
      detailed data were collected on the most recent event. RESULTS: Of the 400
      nurses, 313 (78.3%) reported experiencing at least one NI, 110 (27.5%) reported
      at least one NI within the last 12 months, and 44 (40% of 110) reported multiple
      NI. Nearly two-thirds of these injuries (n = 73/110; 66.4%) were punctures that
      drew blood, resulting in one case of contracted hepatitis C. The cumulative
      annual incidence of NI events was 448 NI per 1000 nurses. Nurses reported the
      injury in adherence with existing regulations and policies in only 21.8% of the
      cases. Disposable syringes were involved in 88 (80%) of the NI events. In half of
      the injuries (n = 55), the needled device was equipped with a safety feature that
      was ineffective, primarily because it was not fully activated (n = 47/55; 85.5%)
      or it malfunctioned (n = 2-5; 3.6-9.1%). NI most commonly occurred while nurses
      were injecting insulin (n = 33; 30%). In the 2 weeks following their NI, 60.1% of
      nurses noted that they were more afraid of needled devices than before the injury
      and 41.8% felt anxious, depressed, or stressed. As a direct result of the NI,
      nurses missed 77 days of work. CONCLUSIONS: This study is the first to show the
      relatively high risk both of NI and of NI that draws blood among nurses injecting
      insulin with a disposable syringe and confirms previous incidence estimates of NI
      among nurses. Additionally, this study reveals significant post-NI emotional
      distress, suggests significant under-reporting of NI to hospital officials, and
      demonstrates the need for a more effective needle safety device.

PMID- 15969874
TI  - Revealing the multidimensional framework of the Minnesota nicotine withdrawal
      scale.
AB  - OBJECTIVES: The version of the Minnesota Nicotine Withdrawal Scale (MNWS) under
      consideration consists of nine items. No psychometric analyses of this version
      have been published. The objectives of this investigation were to perform a
      factor analysis and to further assess the psychometric properties of the MNWS.
      RESEARCH DESIGN AND METHODS: Data came from three Phase II clinical trials on
      varenicline, developed for smoking cessation, in a sample of smokers. Exploratory
      factor analysis was used to examine the structure of the MNWS in the first
      completed study (n = 626) over various time periods. The postulated factor
      structure was then tested in a set of confirmatory analyses conducted on two
      subsequent studies (n = 627, n = 312). The proposed structure was further
      evaluated through construct validity and reliability analyses. MAIN OUTCOME
      MEASURES: The nine items of the MNWS included the following: urge to smoke
      (craving); depressed mood; irritability, frustration, or anger; anxiety;
      difficulty concentrating; restlessness; increased appetite; difficulty going to
      sleep; and difficulty staying asleep. Each item was rated by a subject on an
      ordinal scale from 0 (not at all) to 4 (extreme). RESULTS: Scree plots and
      rotated factor patterns from the exploratory factor analyses revealed two multi
      item domains--Negative Affect with four items and Insomnia with two items--and
      three individual items (Craving, Restlessness, Increased Appetite). Confirmatory
      factor analyses supported the structure with fit indexes exceeding 0.90. The
      multidimensional framework of the MNWS correlated as expected with health status,
      depicted an expected course of withdrawal symptoms over time, predicted the
      sensitivity of withdrawal symptoms on subsequent cessation, and produced internal
      reliability estimates above 0.70. CONCLUSIONS: Evidence is obtained to support
      the validity and reliability of the multidimensional structure of the nine-item
      MNWS. The data suggest that the MNWS has individual constructs on Negative Affect
      (depressed mood; irritability, frustration, or anger; anxiety; difficulty
      concentrating), Insomnia (difficulty going to sleep; difficulty staying asleep),
      Craving, Restlessness, and Increased Appetite. As such, analyzing each construct
      separately would strengthen the analysis of the popular MNWS.

PMID- 15969875
TI  - Risk of pneumonia and other complications of influenza-like illness in patients
      treated with oseltamivir.
AB  - BACKGROUND: Clinical trials suggest that the risk of pneumonia and other sequelae
      of influenza may be reduced in patients using oseltamivir. RESEARCH DESIGN AND
      METHODS: This retrospective cohort study used U.S. health insurance claims data.
      Patients were grouped into three cohorts: (1) diagnosed with influenza-like
      illness (ILI) and received a dispensing of oseltamivir; (2) diagnosed with ILI
      but received no antiviral medication; and (3) received oseltamivir without a
      physician diagnosis of ILI. Baseline factors assessed included demographics,
      history of drug dispensings, diagnoses, and vaccinations. MAIN OUTCOME MEASURES:
      Outcomes included diagnosis of pneumonia, dispensing of an antibiotic, or
      hospitalization within 30 days after an ILI diagnosis or oseltamivir dispensing.
      RESULTS: The adjusted hazard ratio for ILI with oseltamivir compared to ILI
      without antivirals for pneumonia was 0.72 (95% CI, 0.60-0.86), for antibiotic
      dispensing was 0.89 (95% CI, 0.86-0.93), and for hospitalization was 0.74 (95%
      CI, 0.61-0.90). The cohort who received oseltamivir without an ILI diagnosis did
      not differ significantly in risk of any outcome from the ILI with oseltamivir
      cohort. CONCLUSIONS: The risk of pneumonia, antibiotic dispensing, and
      hospitalization was reduced in patients with ILI who received oseltamivir
      compared to no antiviral therapy. These findings were based on health care claims
      only and have not been verified through medical record review.

PMID- 15969876
TI  - Single-dose and steady-state bioequivalence of fexofenadine and pseudoephedrine
      combination tablets compared with individual formulations in healthy adults.
AB  - OBJECTIVE: A 24-h extended-release formulation of fexofenadine HCl 180
      mg/pseudoephedrine HCl 240 mg (FEX 180 mg/PSE 240 mg) has recently been approved
      by the US Food and Drug Administration for symptom relief of seasonal allergic
      rhinitis, including nasal congestion. When considering a combination formulation,
      it is important to confirm that the metabolism and pharmacokinetics of the drugs
      remain unchanged when combined. Thus, the aim of this study was to evaluate
      single-dose and steady-state bioequivalence of FEX 180 mg/PSE 240 mg 24-h
      compared with the individual formulations taken concurrently. RESEARCH DESIGN AND
      METHODS: This was an open-label, randomized, two-treatment, two-period, 10-day,
      crossover study. In Treatment A, healthy subjects received a single, oral dose of
      FEX 180 mg/PSE 240 mg combination tablet on Day 1 followed by 6 days of once
      daily dosing beginning on Day 4. Participants in Treatment B were concurrently
      administered a single oral dose of FEX 180 mg immediate-release tablet and a PSE
      240 mg extended-release tablet with a similar dosing schedule. After an 8-day
      washout period, subjects crossed over to the alternate treatment. Plasma
      concentrations of FEX and PSE were determined using high-performance liquid
      chromatography/mass spectrometry. RESULTS: Pharmacokinetic parameters AUC0
      infinity1 and Cmax1 following a single-dose (Day 1, dose 1), Cmax7, AUC0-24(7) at
      steady-state and Cmin7 measured at the end of the dosing interval (Day 9, dose 7)
      revealed bioequivalence between FEX 180 mg/PSE 240 mg combination tablet and the
      individual components taken concurrently. The 90% confidence intervals for the
      treatment ratios fell entirely within the bioequivalence range (80% to 125%). The
      combination tablet was well tolerated by all subjects, with a safety profile
      comparable to the individual components. CONCLUSIONS: These findings demonstrate
      that the pharmacokinetics of the new 24-h FEX 180 mg/PSE 240 mg combination
      formulation are bioequivalent to the concurrent administration of the individual
      drug components. Furthermore, both treatments were well tolerated in this
      population.

PMID- 15969877
TI  - Antioxidant effect of atorvastatin is independent of PON1 gene T(-107)C, Q192R
      and L55M polymorphisms in hypercholesterolaemic patients.
AB  - BACKGROUND: Serum paraoxonase (PON1), a high density lipoprotein (HDL)-bound
      antioxidant enzyme, plays a role in atherosclerosis. An increase in PON1 activity
      has been reported following statin treatment. OBJECTIVE: In the present study the
      following factors were evaluated: the influence of PON1 gene Q192R, L55M and T(
      107)C polymorphisms on the response of LDL oxidisability and PON1 activity to
      atorvastatin treatment. RESEARCH DESIGN AND METHODS: 205 Sicilian subjects with
      primary hypercholesterolaemia (HCh) and 69 healthy subjects as controls were
      concurrently enrolled. Hypercholesterolaemic patients were randomly divided into
      two groups: an atorvastatin group (10 mg/day atorvastatin) and a placebo group.
      Lipid profile, markers of LDL resistance to in vitro oxidation (lag-phase,
      oxidation rate and thiobarbituric acid-reactive substances), vitamin E content in
      LDL, PON1 activity and genotypes in both HCh and control subjects were determined
      at baseline. The same parameters were measured again after 3 weeks of treatment
      in both the atorvastatin and placebo groups. RESULTS: HCh subjects showed
      significantly lower LDL resistance to oxidation, vitamin E content and PON1
      activity levels than controls. A strong association was found among PON1 T(-107)C
      genotypes, LDL susceptibility to oxidation, vitamin E content and PON1 activity.
      After treatment, the atorvastatin group displayed a significant decrease in total
      cholesterol, LDL-cholesterol levels, and LDL susceptibility to oxidation, and an
      increase in vitamin E content and PON1 activity, compared with baseline values.
      Unlike PON1 activity levels, no difference among PON1 gene polymorphisms and
      reduction in markers of LDL oxidisability was observed. CONCLUSIONS: These
      results show, for the first time, that atorvastatin is able to improve the
      resistance to LDL oxidation independently of PON1 gene polymorphism.

PMID- 15969878
TI  - Systematic review comparing meropenem with imipenem plus cilastatin in the
      treatment of severe infections.
AB  - OBJECTIVE: To compare the effectiveness of meropenem with imipenem plus
      cilastatin in the treatment of severe infections. DATA SOURCES: CENTRAL, EMBASE
      and MEDLINE were searched for abstracts and papers. All searching was completed
      in March 2004. No restriction was placed on language. STUDY SELECTION: Randomized
      controlled trials of adult patients with severe infections treated with meropenem
      or imipenem plus cilastatin at an equal dose, on a gram-for-gram basis, and with
      the same dosing regimen. DATA EXTRACTION: Two reviewers independently assessed
      papers against the inclusion/exclusion criteria and for methodological quality
      with differences in opinion adjudicated by a third party. Data were extracted on
      clinical response, bacteriologic response, mortality and adverse events. DATA
      SYNTHESIS: A total of 27 trials met the inclusion criteria. Meta-analyses were
      carried out using a Fixed Effects model. Results demonstrated that when compared
      to imipenem plus cilastatin, meropenem is associated with a significantly greater
      clinical response (Relative Risk 1.04; 95% Confidence Interval: 1.01-1.06), a
      significantly greater bacteriologic response (RR 1.05; 95% CI: 1.01-1.08), a non
      significant reduction in mortality (RR 0.98; 95% CI: 0.71-1.35), and a
      significantly lower adverse event rate (RR 0.87; 95% CI: 0.77-0.97). CONCLUSIONS:
      This systematic review demonstrates that meropenem compared to imipenem plus
      cilastatin has a significantly greater clinical and bacteriologic response with a
      significant reduction in adverse events. There was no evidence of heterogeneity
      or publication bias and the analyses were robust to changes in the
      inclusion/exclusion criteria and use of a Random Effects model.

PMID- 15969879
TI  - Stimulation of P19CL6 with multiple reagents induces pulsating particles in vivo.
AB  - OBJECTIVE: Injection of stem cells into ischaemic areas of the heart is expected
      to be an effective method for myocardial regeneration. The embryogenic carcinoma
      (EC) cell line P19CL6 is known to differentiate into cardiomyocytes when cultured
      with dimethyl sulfoxide (DMSO) and is expected to be a promising source for
      regenerative therapy in cardiac disease. To establish a high-yield method of
      cardiomyocyte differentiation, P19CL6 cells were double-stimulated with 5
      azacytidine. Double stimulation-induced cardiomyocytes were also transplanted
      into ectopic sites in mice and their function evaluated. METHODS AND RESULTS: To
      induce differentiation under adherent conditions, P19CL6 cells were incubated in
      growth medium with 10 microM 5-azacytidine for 24 h. After 5-azacytidine
      treatment, P19CL6 cells were incubated with 1% DMSO for nine days until they
      began to pulsate. Prior to transplantation, cells were treated again with 5
      azacytidine. Differentiated cells were injected into the greater omentum, para
      aorta region of the retroperitoneum and peri-femoral artery of adult BALB/c nude
      mice. Nine days after transplantation, irregularly pulsating tissues at a rate
      slower than the host heart were observed in the transplanted sites. Light
      microscopy showed formation of cardiac muscle tissues originating from P19CL6
      cells. Differentiated cardiomyocytes were positive for cardiac troponin I,
      cadherin and alpha-smooth muscle actin, and the expressions of Csx/Nkx2.5 and
      GATA4 mRNAs were up-regulated. Electron microscopy demonstrated components
      specific to cardiomyocytes, such as Z-bands, desmosomes, fasciae adherens,
      myofibrils and mitochondria, which confirmed successful heterotopic cardiac
      muscle differentiation from P19CL6 cells. CONCLUSION: This study demonstrated
      high-yield cardiac muscle differentiation of P19CL6 by 5-azacytidine and DMSO
      double stimulation and successful formation of cardiac muscle-like tissue by
      ectopic transplantation of cardiomyocytes derived from P19CL6 into the
      retroperitoneal area as well as into the peripheral vessel area.

PMID- 15969880
TI  - Costs and consequences of using pamidronate compared with zoledronic acid in the
      management of breast cancer patients in the UK.
AB  - OBJECTIVE: To estimate the costs and consequences of using pamidronate compared
      to zoledronic acid in the prophylactic management of skeletal morbidity among
      breast cancer patients in the UK. DESIGN AND SETTING: This was a modelling study
      performed from the perspective of the UK's National Health Service (NHS).
      METHODS: Published clinical outcomes from a comparative study were combined with
      resource utilisation estimates derived from a panel of clinicians. This enabled
      the construction of a decision model depicting the management of patients with
      breast cancer receiving antineoplastic therapy who are 18 years of age or above
      and who have at least one bone metastasis (lytic or mixed). There are no
      significant differences in outcome between using pamidronate and zoledronic acid
      in breast cancer patients. Therefore, a cost minimisation analysis was performed
      to identify the treatment strategy that achieves the same outcome for least cost.
      The expected time attributable to a pamidronate and zoledronic acid infusion was
      also estimated. MAIN OUTCOME MEASURES AND RESULTS: Starting treatment with
      pamidronate among patients receiving chemotherapy is expected to lead to a
      healthcare cost of 6046 pounds over 12 months compared to 6981 pounds with
      zoledronic acid. In comparison, for patients receiving hormonal therapy, starting
      treatment with pamidronate is expected to lead to a healthcare cost of 5401
      pounds over 12 months compared to 6043 pounds with zoledronic acid. This cost
      difference is primarily due to the lower acquisition cost of pamidronate and
      fewer tests among pamidronate-treated patients. Accordingly, pamidronate affords
      a less expensive management modality. Multivariate analysis showed the expected
      time attributable to a pamidronate infusion to be 110 to 277 minutes compared
      with 136 to 296 minutes for a zoledronic acid infusion. CONCLUSION: Use of
      pamidronate instead of zoledronic acid affords an economic benefit to the NHS.
      Moreover, published clinical trials show no statistical difference between
      pamidronate and zoledronic acid at 1 year. Hence, within the limitations of our
      model and the published evidence, pamidronate is the preferred first-line
      intravenous bisphosphonate for use in breast cancer patients receiving
      antineoplastic therapy who are 18 years of age or above and who have at least one
      bone metastasis (lytic or mixed).

PMID- 15969881
TI  - Cost effectiveness of cilostazol compared with naftidrofuryl and pentoxifylline
      in the treatment of intermittent claudication in the UK.
AB  - OBJECTIVE: To estimate the cost effectiveness of cilostazol (Pletal) compared to
      naftidrofuryl and pentoxifylline (Trental) in the treatment of intermittent
      claudication in the UK. DESIGN AND SETTING: This was a modelling study on the
      management of patients with intermittent claudication who are 40 years of age or
      above and have at least six months history of symptomatic intermittent
      claudication, secondary to lower extremity arterial occlusive disease. The study
      was performed from the perspective of the UK's National Health Service (NHS).
      METHODS: Clinical outcomes attributable to managing intermittent claudication
      were obtained from the published literature and resource utilisation estimates
      were derived from a panel of vascular surgeons. Using decision analytical
      techniques, a decision model was constructed depicting the management of
      intermittent claudication with cilostazol, naftidrofuryl and pentoxifylline over
      24 weeks in the UK. The model was used to estimate the cost effectiveness (at
      2002/2003 prices) of cilostazol relative to the other treatments. MAIN OUTCOME
      MEASURES AND RESULTS: Starting treatment with cilostazol instead of naftidrofuryl
      is expected to increase the percentage improvement in maximal walking distance by
      32% (from 57% to 75%) for a 12% increase in NHS costs (from 801 pounds sterling
      to 895 pounds sterling). Treatment with cilostazol instead of pentoxifylline is
      expected to increase the percentage improvement in maximal walking distance by
      67% (from 45% to 75%) and reduce NHS costs by 2% (from 917 pounds sterling to 895
      pounds sterling). Treatment with naftidrofuryl instead of pentoxifylline is
      expected to increase the percentage improvement in maximal walking distance by
      27% (from 45% to 57%) and decrease NHS costs by 14% (from 917 pounds sterling to
      801 pounds sterling). CONCLUSION: Within the limitations of our model, starting
      treatment with cilostazol is expected to be a clinically more effective strategy
      for improving maximal walking distance at 24 weeks than starting treatment with
      naftidrofuryl or pentoxifylline and potentially the most cost effective strategy.
      Moreover, the acquisition cost of a drug should not be used as an indication of
      the cost effectiveness of a given method of care.

PMID- 15969882
TI  - Variability of fine particle dose and lung deposition of budesonide delivered
      through two multidose dry powder inhalers.
AB  - OBJECTIVE: To assess the reliability of dosing through two budesonide multidose
      dry powder inhalers (DPI) as derived from the in-vitro variability of the fine
      particle dose (FPD) and the in-vivo variability of the lung deposition at
      different flow rates. METHODS: The same two DPIs [device N (Novolizer) and device
      T (Turbuhaler)] were compared in both studies. In the in-vitro study, the
      variability of the FPD, measured at flow rates of 30-100 L/min, was determined
      for equal flow rates and at comparable maximal inspiratory pressures (MIP). In
      the in-vivo study in healthy subjects (scintigraphic, randomised, crossover
      design) the variability of the lung deposition was determined at targeted flow
      rates of 45, 60 and 90 L/min for device N, and at 60 L/min for device T. RESULTS:
      The variability of the FPD was lower with device N than with device T by 34%-86%.
      The differences were statistically significant for flow rates of 60, 70, 90 and
      100 L/min (not significant for 40, 50 and 80 L/min) in the in-vitro study.
      Results for comparable MIPs showed analogous differences (79%, p = 0.004, at the
      clinically relevant MIP of 4.5 kPa). The variability of the lung deposition was
      clearly lower with the device N than with the device T. The difference was
      statistically significant (p = 0.029) at a comparable targeted flow rate of 60
      L/min. CONCLUSIONS: Thus, this study showed that device N is likely to improve
      the reliability of inhalation therapy by reducing both the variability of the
      delivered drug and that of the lung deposition. The reliability of inhalation
      therapy and consequently the quality of long-term control of asthma and the
      patient's compliance might improve when choosing the DPI with the better
      characteristics.

PMID- 15969883
TI  - Is it possible to make cross-study comparisons of urinary continence rates in
      patients with overactive bladder?
AB  - Several antimuscarinic agents are available for the treatment of overactive
      bladder but there are few head-to-head studies to guide physicians in choosing
      one over another. Here we propose ways in which logical adjustments can be made
      to account for differences in disease severity and placebo effects when
      considering continence data to allow estimation of relative effectiveness across
      studies.

PMID- 15969884
TI  - Management of hypertension and hypercholesterolaemia in primary care in The
      Netherlands.
AB  - OBJECTIVE: Screening, treatment and monitoring guidelines for hypertension and
      hypercholesterolaemia have been developed to assist physicians in providing
      evidence-based health care. We conducted a retrospective study to assess the
      management of patients with these single or combined conditions. RESEARCH DESIGN
      AND METHODS: This was a retrospective cohort study conducted using data from the
      Integrated Primary Care Information (IPCI) project based in The Netherlands.
      Management of hypertension and hypercholesterolaemia was assessed from 2000-2003
      by measuring the numbers of patients screened for these conditions, treated
      pharmacologically and monitored for treatment success. RESULTS: Approximately
      11%, 3% and 10% of participants were eligible for screening for hypertension
      alone, hypercholesterolaemia alone and both conditions, respectively. Blood
      pressure screening was high in patients eligible for both blood pressure and
      cholesterol screening (> 86%), whereas cholesterol screening was low (< 56%).
      Among patients newly identified with hypertension or hypercholesterolaemia who
      were eligible for pharmacotherapy, 29% and 43% respectively were not treated
      within one year of diagnosis. Undertreatment was significantly lower in patients
      with both conditions (24% and 37% for antihypertensive and lipid-lowering
      treatment, respectively and 28% were not treated for both). Among newly treated
      patients, in the first year of treatment there was no record of a blood pressure
      or cholesterol assessment, for 35% and 72%, respectively. CONCLUSION: Management
      was sub-optimal in patients with hypertension or hypercholesterolaemia as well as
      in those with both of these conditions. The results of this study are likely to
      be widely applicable, particularly to other European and industrialised countries
      that have similar free-access health care systems to The Netherlands.

PMID- 15969885
TI  - An observational study of health-related quality of life and pain outcomes in
      chronic low back pain patients treated with fentanyl transdermal system.
AB  - BACKGROUND: The analgesic effect of long-acting opioids, such as transdermal
      fentanyl, has been demonstrated in patients with cancer, neuropathic pain and
      chronic low back pain (CLBP). However, the broader effect of long-acting opioids
      on the patient's health-related quality of life (HRQoL) is less well known.
      OBJECTIVE: To evaluate HRQoL outcomes in CLBP patients treated with transdermal
      fentanyl. RESEARCH DESIGN AND METHODS: An observational study was conducted at 17
      clinical centers in the US. Eligible patients had CLBP diagnosis for at least 3
      months and were taking short-acting opioids chronically, and then initiated
      transdermal fentanyl treatment. Patients completed the Treatment Outcomes in Pain
      Survey (TOPS), which includes the SF-36 Health Survey, at baseline and > or = 9
      weeks of treatment. The HRQoL burden of CLBP was determined by comparing CLBP
      patients' SF-36 scores to the general US population and low back pain patient
      norms. HRQoL outcomes were determined by comparing baseline and follow-up TOPS
      and SF-36 scores. Additionally, HRQoL outcomes were evaluated across patient
      groups stratified by changes in pain intensity ratings as measured by an 11-point
      numerical rating scale. RESULTS: At baseline CLBP patients (N = 131) scored one
      to-two standard deviations (SD) below age and gender adjusted SF-36 general
      population norms (MANOVA F = 127.1, p < 0.0001) and significantly lower than low
      back pain norms (MANOVA F = 125.3, p < 0.0001). At follow-up, significant
      improvement (p < 0.05) was observed on six of the SF-36 scales and both SF-36
      summary measures and five of the six TOPS pain-related scales. The magnitude of
      change in scores in effect size units among these scales ranged from 0.17 to
      0.80, which are considered small to large effect size changes. HRQoL score
      improvement was greatest among patients experiencing the greatest pain relief.
      CONCLUSION: CLBP patients who chronically used short-acting opioids showed
      tremendous HRQoL burden. Favorable HRQoL outcomes were observed among patients
      who reported pain relief.

PMID- 15969886
TI  - Improving asthma control in patients suboptimally controlled on inhaled steroids
      and long-acting beta2-agonists: addition of montelukast in an open-label pilot
      study.
AB  - BACKGROUND: Airway inflammation and symptoms often persist in asthma patients
      despite treatment with inhaled corticosteroids (ICS) and long-acting beta2
      agonists (LABA). It is hypothesized that the leukotriene receptor antagonist
      montelukast, treating a pathway of inflammation distinct from that of ICS, might
      confer additional benefit. OBJECTIVE: To evaluate the efficacy of montelukast in
      improving asthma control in patients symptomatic on a fixed-association (FA)
      medium dose of ICS and LABA. METHODS: A 2-month, open-label, real-life
      observational study was undertaken by 131 Belgian pulmonologists. Patients (> or
      = 15 years old) suffering from persistent asthma (pre-bronchodilator FEV1 > or =
      60% of predicted value) and insufficiently controlled on a FA therapy of
      fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg
      daily as add-on therapy. Asthma control was assessed by the standardized Juniper
      asthma control questionnaire (ACQ) at baseline and after a 2-month treatment with
      montelukast. Global evaluation of therapy was made both by the patients and
      physicians. RESULTS: A total of 313 patients were eligible for analysis. Forty
      nine per cent received inhaled fluticasone/salmeterol and the rest
      budesonide/formoterol. Mean ACQ score decreased significantly on montelukast
      (13.9 +/- 5.1 at baseline versus 7.4 +/- 4.7 on montelukast, p < 0.001), with a
      significant improvement in all individual symptom scores (p < 0.001) and in pre
      bronchodilator FEV1 score (from 2.2 +/- 1.5 to 1.6 +/- 1.4; p < 0.001). Parallel
      to these results, 78.6% of the patients reported a global improvement of their
      asthma. The same proportion of improvement was observed in the global evaluation
      made by the physicians (kappa = 0.66). CONCLUSION: This pilot study suggests that
      addition of montelukast in patients symptomatic on a FA of ICS and LABA may
      result in significant improvements in asthma control. A randomised, placebo
      controlled clinical trial seems warranted.

PMID- 15969887
TI  - The cognitive effects of cholinesterase inhibitor treatment in every-day
      practice.
AB  - OBJECTIVE: Cholinesterase inhibitors (ChEIs) are the treatment of choice in
      Alzheimer's disease (AD). Their efficacy has been proven in many clinical trials.
      The aim of the present study was to confirm their cognitive benefit in every day
      practice as to whether it is similar to that expected from clinical trials.
      PATIENTS AND METHODS: We reviewed the files of 41 patients suffering from AD or
      mixed dementia and treated by ChEIs in terms of every day practice. RESULTS:
      During the first year MMSE scores remained better than or at baseline levels.
      Following that a gradual decline was noted. However, at any time point, the
      observed scores were significantly better than the expected ones calculated
      according to the pre-treatment rate of decline. The post-treatment rate of
      decline was significantly better than the pre-treatment one, while progression to
      the next stage of dementia was delayed by 8 months. CONCLUSION: The present
      observations from every-day practice indicate that there is a small but
      significant effect of ChEIs in cognition, similar to that observed in clinical
      trials. Furthermore, a small but significant delay in dementia progression may
      occur after treatment with ChEIs.

PMID- 15969888
TI  - A pilot study comparing the purity, functionality and isoform composition of
      alpha-1-proteinase inhibitor (human) products.
AB  - OBJECTIVE: Alpha-1-proteinase deficiency predisposes affected individuals to
      early onset pulmonary emphysema, and is treated with an alpha-1-proteinase
      inhibitor (A1-PI) from pooled human plasma. The objective of this pilot study was
      to assess analytical parameters of the three A1-PI products (Aralast, Prolastin,
      Zemaira) that may impact on clinical efficacy, safety, and convenience. These
      included: purity of the preparation; nature of impurities; functionality; and
      isoform composition. METHODS: Purity was evaluated using reverse phase and size
      exclusion chromatography high performance liquid chromatography (RP-HPLC and SEC
      HPLC), capillary zone electrophoresis (CZE), sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, sodium dodecyl sulfate capillary gel
      electrophoresis and Western blot analysis. The identity of protein impurities was
      determined by immunonephelometry; functionality by calculating the ratio of mg
      active A1-P1 present (by anti-neutrophil elastase activity assay) to the mg
      antigenic A1-PI (by immunonephelometry); and normality of the A1-PI isoform
      pattern by isoelectric focusing (IEF). Three samples of Zemaira and one sample
      each of Aralast and Prolastin were available for analysis. RESULTS: Zemaira had
      the highest specific activity. Using RP-HPLC analysis Zemaira averaged 99%
      purity, Aralast 70% and Prolastin less than 62%. Using SEC-HPLC Zemaira was
      95.98% monomeric, Prolastin 79.00% and Aralast 63.55%. Prolastin had lower
      activity/mg antigenic A1-PI than the other two products. A shift in isoforms in
      Aralast was suggested by the results of CZE, and was confirmed by IEF.
      CONCLUSIONS: Zemaira demonstrated greater purity compared with Aralast and
      Prolastin. Prolastin had more inactive A1-PI than Zemaira or Aralast. Isoform
      ratios appeared to be altered in Aralast. The results from this pilot study
      warrant further investigation.

PMID- 15969889
TI  - Optimising antiemetic therapy: what are the problems and how can they be
      overcome?
AB  - BACKGROUND: Management of chemotherapy- or radiotherapy-induced emesis has
      improved significantly following the introduction of the 5-HT3-receptor
      antagonists. Prophylactic use of these agents is recommended for the prevention
      of both chemotherapy- and radiotherapy-induced nausea and vomiting, given with a
      corticosteroid. Despite these advances, nausea and vomiting remain among the most
      feared and debilitating adverse effects of cytotoxic therapy. The shift towards a
      more elderly population of patients with cancer presents additional
      considerations for supportive care, with an emphasis on achieving control of
      nausea and vomiting, whilst minimising toxicity and avoiding drug-drug
      interactions. This review presents some of the key issues for consideration in
      optimising antiemetic therapy. The PubMed search engine was used to search for
      relevant literature (up to December 2004) and relevant international congress
      materials collected during 2003 and 2004. SCOPE: While the early stages of nausea
      and vomiting are 5-HT-mediated, identification of a role for substance P in late
      emesis has led to the development of the NK1-receptor antagonist, aprepitant. As
      a new agent, the clinical profile of aprepitant is still being explored,
      including its interaction with concomitant medications. Patients who achieve good
      control of acute and late-acute nausea and vomiting have a reduced risk of
      experiencing delayed onset symptoms, emphasising the importance of prophylactic
      management with effective agents. Although the 5-HT3-receptor antagonists are
      widely considered to have equivalent efficacy, they vary in half-life and the
      nature of antagonism at receptors. Their metabolic profiles also differ, with
      cytochrome P450 (CYP) metabolism affecting their propensity for drug-drug
      interactions. Several sets of guidelines are available that outline
      recommendations for selection and use of antiemetic therapy. However, under-use
      of 5-HT3 receptor antagonists has been reported in both the radiotherapy and
      chemotherapy settings, and some commonly used doses may be suboptimal.
      CONCLUSION: In optimising antiemetic therapy, wider implementation of guidelines
      is desirable, as is consideration of each patient's individual needs. Safety and
      tolerability of supportive care medications should be a key consideration, and
      cardiovascular warnings and the possibility of drug-drug interactions should be
      given sufficient consideration, particularly in view of the older age of the
      population with cancer.

PMID- 15969890
TI  - Comparative analytical characterization of two commercial human follicle
      stimulating hormones extracted from human urine.
AB  - OBJECTIVE: Pharmaceutical preparations of human menopausal gonadotrophin (hMG),
      urine-derived follicle-stimulating hormone (u-FSH) and highly purified u-FSH (u
      FSH-HP) have been available since the early 1960s and the mid 1980s and 1990s,
      respectively. Another commercial preparation of u-FSH-HP, Folyrmon P, was
      launched in Japan in 1999. The aim of this study is to assess the purity of
      Folyrmon P and to compare it with Fertinorm-P, another commercial preparation of
      u-FSH-HP that has been available since 1993. METHODS: Folyrmon P and Fertinorm-P
      were assessed for total protein content, biological activity, immunological
      activity, specific activity, purity and levels of protein contamination. RESULTS:
      Folyrmon P, which is extracted from the urine of post-menopausal women, has a
      specific activity of between 4000 and 5000 IU/mg, while Fertinorm-P, which is
      also manufactured from the urine of post-menopausal women, has a specific
      activity of at least 10,000 IU/mg. It has been well documented that commercially
      available hMG and u-FSH preparations can contain a number of urine-derived
      protein contaminants. This also proves to be the case for Folyrmon P, in which
      contaminant proteins other than FSH were shown to be present. It was also
      demonstrated that both preparations, Folyrmon P and Fertinorm-P, contained high
      levels of oxidized FSH. CONCLUSIONS: The low specific activity and high level of
      contaminants in Folyrmon P indicate that this u-FSH is not highly purified.
      Overall, Fertinorm-P, with higher specific activity and lower levels of
      contaminant proteins, appears to be of higher quality compared with Folyrmon P.

PMID- 15969891
TI  - Effect of bosentan treatment on surrogate markers in pulmonary arterial
      hypertension.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of the oral dual
      ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in
      patients with pulmonary arterial hypertension (PAH). DESIGN AND SETTING:
      Prospective, open label, uncontrolled study in a University Hospital in Brazil.
      POPULATION: Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5
      in WHO functional class II, 10 in class III). METHODS: All patients were
      investigated at baseline and after 16 weeks of bosentan treatment. We used the
      following surrogate markers for patients' evaluation: 6-min walk test, quality of
      life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic
      peptide) fraction levels in blood. RESULTS: Between the evaluation at baseline
      and week 16, the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137
      m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved.
      Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p =
      0.01). CONCLUSION: The study suggests that bosentan treatment results in the
      improvement of different kinds of surrogate markers independently of their
      specificity to reflect functional capacity, quality of life and myocardial
      stress. It is concluded that the combined use of these different markers may be
      an alternative endpoint for future short duration clinical trials.

PMID- 15969892
TI  - Quetiapine monotherapy for mania associated with bipolar disorder: combined
      analysis of two international, double-blind, randomised, placebo-controlled
      studies.
AB  - OBJECTIVE: To evaluate the efficacy and safety of quetiapine monotherapy for
      mania in bipolar disorder by an a priori defined combined analysis of data from
      two placebo-controlled studies. METHOD: The intent-to-treat (ITT) populations
      from two studies of patients with DSM-IV bipolar I disorder, manic episode,
      randomised to 12 weeks of double-blind treatment with quetiapine (up to 800
      mg/day) or placebo were combined. The primary efficacy endpoint was change in
      Young Mania Rating Scale (YMRS) score from baseline to Day 21. Secondary
      endpoints included change from baseline in YMRS to Day 84, YMRS response and
      remission rates and change from baseline to Days 21 and 84 in the Montgomery
      Asberg Depression Rating Scale (MADRS), Clinical Global Impressions (CGI),
      Clinical Global Impressions-Bipolar (CGI-BP) and the Positive and Negative
      Syndrome Scale (PANSS). These endpoints were analysed as continuous variables,
      using an analysis of covariance (ANCOVA), with the baseline as covariate. In
      order to account for any difference in response between studies, the analyses
      were stratified by study as a fixed effect, and centre as a random effect. The
      Cochran-Mantel-Haenszel test was used to analyse binary variables. A chi square
      test was used to compare the frequency of adverse events between the treatment
      groups. RESULTS: The combined analysis included a total of 403 patients from two
      quetiapine monotherapy studies in patients with bipolar I disorder. A significant
      improvement in YMRS score was observed from Day 4 (p = 0.021) onward in the
      quetiapine group compared with placebo. The treatment advantage of quetiapine
      over placebo continued to increase to Day 21 (p < 0.001) and Day 84 (p < 0.001).
      Significantly more quetiapine-treated than placebo-treated patients achieved a
      response (p < 0.001). The average quetiapine dose in responders was approximately
      600 mg daily. Of adverse events occurring in > or = 5% of patients, quetiapine
      treated patients had a significantly greater incidence versus placebo of
      somnolence (16.3% vs. 4.0%), dry mouth (15.8% vs. 3%), weight gain (9.1% vs.
      1.5%) and dizziness (6.7% vs. 2.5%). CONCLUSIONS: The data from this combined
      analysis support the results from the individual studies and indicate that
      quetiapine monotherapy is effective across a broad range of mood symptoms, fast
      acting and well tolerated in the treatment of mania.

PMID- 15969893
TI  - Long-acting blood pressure reduction by candesartan cilexetil in patients with
      hypertension.
AB  - Candesartan cilexetil is a highly potent and long-acting angiotensin II type I
      (AT1) receptor antagonist. This short review summarises results of clinical
      studies focusing on the duration of action of candesartan cilexetil. Results of
      previous clinical studies indicate that candesartan has the property to maintain
      a sustained blood pressure reduction for up to 48 h after dosing. Since lack of
      compliance is a known problem in patients with hypertension, these findings could
      be of particular clinical relevance.

PMID- 15969894
TI  - Benzodiazepines and anxiety disorders: a review for the practicing physician.
AB  - OBJECTIVES AND SCOPE: The objective of this article is to briefly review for
      practicing clinicians differences among the benzodiazepines (BZDs) that are
      commonly used to treat anxiety, the efficacy of BZDs in various anxiety
      disorders, and potential safety issues associated with BZDs, including adverse
      events, tolerance, dependence, and withdrawal. METHODOLOGY: Information for this
      review was obtained using literature searches through PubMed (1966-2004), Google,
      and the Food and Drug Administration Catalog of Approved Drugs. Data sources were
      searched for information regarding anxiety disorders and the safety and efficacy
      of BZDs. Wherever possible and appropriate, information from randomized
      controlled trials was given priority. FINDINGS: Benzodiazepines have demonstrated
      efficacy in treating patients with anxiety disorders, with varying degrees of
      efficacy. Use of BZDs is advantageous because they have a quick onset of action
      and are generally well tolerated. Extended-release formulations of BZDs may be
      particularly advantageous in some patients with anxiety as they allow for
      maximization of a drug's therapeutic window with consistent serum drug
      concentrations. CONCLUSIONS: BZDs remain a mainstay in the treatment of anxiety,
      as both monotherapy and adjunctive therapy. Factors to consider prior to
      prescribing a BZD include the patient's diagnosis, as well as drug
      characteristics, including the potential for interactions with other drugs, the
      risk of dependence and withdrawal, and the required frequency of dosing.

PMID- 15969895
TI  - Effects of nilvadipine and amlodipine in patients with mild to moderate essential
      hypertension: a double blind, prospective, randomised clinical trial.
AB  - OBJECTIVE: This double blind, prospective, randomised, parallel group clinical
      trial was aimed at investigating the effects of nilvadipine or amlodipine in mild
      to moderate hypertensive patients over a 3-month treatment period. RESEARCH
      DESIGN AND METHODS: Eligible outpatients (supine DBP > or = 90 mmHg and < or =
      110 mmHg and supine SBP < or = 180 mmHg) entered a maximum 15-day placebo run-in
      period and were randomised to receive once daily nilvadipine 8 mg or amlodipine 5
      mg (to be doubled in the case of lack of response at day 30). Follow-up visits
      with measurement of supine and orthostatic blood pressure and heart rate were
      performed after 15, 30, 60 and 90 days of treatment. Standard laboratory tests
      and 12-lead ECG were performed at study entry and at the end of treatment;
      adverse events were collected at any time. RESULTS: A total number of 168
      patients, 83 in the nilvadipine and 85 in the amlodipine group, took part in the
      study: 15 and 14 in the two groups, respectively, were prematurely withdrawn.
      Supine DBP at endpoint similarly decreases in the two groups (-11.0 +/- 7.1 mmHg
      in the nilvadipine group and -12.7 +/- 8.2 mmHg in the amlodipine group), with no
      significant differences between groups at any time point. Measurements in the
      orthostatic position also did not show between-groups differences. Blood pressure
      was normalised in 61.8% of patients in the nilvadipine group and in 63.0% in the
      amlodipine group; responders to therapy were 64.5% and 69.1% in the two groups,
      respectively. Results of SBP also did not show differences between groups at any
      time point, except a more marked decrease in the amlodipine group compared to
      nilvadipine in the supine measurements at endpoint. A total number of 30 patients
      (36.6%) in the nilvadipine group and 23 (27.1%) in the amlodipine group reported
      adverse events (p = 0.24 between groups), which mainly consisted of vasodilatory
      effects (e.g. oedema, flushing and headache). A favourable lipid profile, i.e. a
      significant (p = 0.002 between groups) decrease of triglycerides levels and an
      increase of HDL-C, was observed in the nilvadipine group, compared with an
      increase of triglycerides in the amlodipine group. No effects on haematology,
      liver and renal function were observed in either group. CONCLUSIONS: Nilvadipine
      or amlodipine produced comparable effects on DBP and shared a similar adverse
      effect profile. A favourable effect on lipid profile was observed following
      nilvadipine treatment.

PMID- 15969896
TI  - The use of ezetimibe in achieving low density lipoprotein lowering goals in
      clinical practice: position statement of a United Kingdom consensus panel.
AB  - There is no doubt that lowering serum cholesterol levels reduces the risk of
      major coronary events. This evidence has led treatment guidelines to set
      progressively lower targets for low density lipoprotein cholesterol (LDL-C).
      However, despite widespread use of statins, substantial numbers of patients do
      not achieve the LDL-C goals. Using higher doses of statins in an attempt to
      achieve these targets may increase the risk of serious adverse effects.
      Furthermore, the use of combination therapy with agents such as bile acid
      sequestrants, niacin and fibrates has been limited by increased potential for
      side effects, drug interactions and poor compliance. Ezetimibe, a selective
      cholesterol transport inhibitor, reduces the intestinal uptake of cholesterol
      without affecting absorption of triglycerides or fat-soluble vitamins. In
      clinical studies, ezetimibe 10 mg, in combination with statins or as monotherapy,
      was well tolerated and reduced LDL-C by 34-53% and 17-18%, respectively. The
      available evidence for ezetimibe is reviewed. The role of ezetimibe in increasing
      the proportion of patients attaining LDL-C treatment goals is discussed.

PMID- 15969897
TI  - Safety, tolerability, and exploratory efficacy of montelukast in 6- to 24-month
      old patients with asthma.
AB  - OBJECTIVE: The purpose of this study was to determine the safety and tolerability
      profile of montelukast 4-mg oral granules compared with placebo in children aged
      6-24 months with asthma. METHODS: This was a randomized, double-blind, placebo
      controlled, parallel-group study. Children 6-24 months of age at first visit with
      a history of at least three episodes of physician-diagnosed asthma or 'asthma
      like' symptoms and in need of controller therapy were randomized to either
      montelukast 4-mg oral granules or placebo once daily in the evening for 6 weeks.
      The primary variables were the frequency of clinical and laboratory adverse
      experiences. The exploratory efficacy endpoints included days without beta
      agonist use, beta-agonist use per day, unscheduled physician or hospital visits
      for asthma, oral corticosteroid rescues for asthma, asthma attacks,
      discontinuation due to worsening of asthma, and total blood peripheral eosinophil
      counts. RESULTS: The most common clinical adverse experiences were upper
      respiratory tract infection, asthma, fever, diarrhea, and vomiting occurring with
      similar frequencies between treatment groups. There were no clinically meaningful
      differences between the two treatment groups in clinical or laboratory adverse
      experiences and no significant differences in frequency of patients with elevated
      serum transaminases. Differences between the montelukast and placebo treatment
      groups in the exploratory efficacy endpoints of days without beta-agonist use,
      oral corticosteroid rescues, emergency care, asthma attacks, and discontinuations
      due to worsening asthma were not significant. CONCLUSIONS: Montelukast, 4-mg oral
      granules, was well tolerated over 6 weeks of treatment in children aged 6-24
      months with asthma.

PMID- 15969899
TI  - How do we evaluate artificial immune systems?
AB  - The field of Artificial Immune Systems (AIS) concerns the study and development
      of computationally interesting abstractions of the immune system. This survey
      tracks the development of AIS since its inception, and then attempts to make an
      assessment of its usefulness, defined in terms of 'distinctiveness' and
      'effectiveness.' In this paper, the standard types of AIS are examined--Negative
      Selection, Clonal Selection and Immune Networks--as well as a new breed of AIS,
      based on the immunological 'danger theory.' The paper concludes that all types of
      AIS largely satisfy the criteria outlined for being useful, but only two types of
      AIS satisfy both criteria with any certainty.

PMID- 15969900
TI  - A machine learning evaluation of an artificial immune system.
AB  - ARTIS is an artificial immune system framework which contains several adaptive
      mechanisms. LISYS is a version of ARTIS specialized for the problem of network
      intrusion detection. The adaptive mechanisms of LISYS are characterized in terms
      of their machine-learning counterparts, and a series of experiments is described,
      each of which isolates a different mechanism of LISYS and studies its
      contribution to the system's overall performance. The experiments were conducted
      on a new data set, which is more recent and realistic than earlier data sets. The
      network intrusion detection problem is challenging because it requires one-class
      learning in an on-line setting with concept drift. The experiments confirm
      earlier experimental results with LISYS, and they study in detail how LISYS
      achieves success on the new data set.

PMID- 15969901
TI  - A study of fitness distance correlation as a difficulty measure in genetic
      programming.
AB  - We present an approach to genetic programming difficulty based on a statistical
      study of program fitness landscapes. The fitness distance correlation is used as
      an indicator of problem hardness and we empirically show that such a statistic is
      adequate in nearly all cases studied here. However, fitness distance correlation
      has some known problems and these are investigated by constructing an artificial
      landscape for which the correlation gives contradictory indications. Although our
      results confirm the usefulness of fitness distance correlation, we point out its
      shortcomings and give some hints for improvement in assessing problem hardness in
      genetic programming.

PMID- 15969902
TI  - The hierarchical fair competition (HFC) framework for sustainable evolutionary
      algorithms.
AB  - Many current Evolutionary Algorithms (EAs) suffer from a tendency to converge
      prematurely or stagnate without progress for complex problems. This may be due to
      the loss of or failure to discover certain valuable genetic material or the loss
      of the capability to discover new genetic material before convergence has limited
      the algorithm's ability to search widely. In this paper, the Hierarchical Fair
      Competition (HFC) model, including several variants, is proposed as a generic
      framework for sustainable evolutionary search by transforming the convergent
      nature of the current EA framework into a non-convergent search process. That is,
      the structure of HFC does not allow the convergence of the population to the
      vicinity of any set of optimal or locally optimal solutions. The sustainable
      search capability of HFC is achieved by ensuring a continuous supply and the
      incorporation of genetic material in a hierarchical manner, and by culturing and
      maintaining, but continually renewing, populations of individuals of intermediate
      fitness levels. HFC employs an assembly-line structure in which subpopulations
      are hierarchically organized into different fitness levels, reducing the
      selection pressure within each subpopulation while maintaining the global
      selection pressure to help ensure the exploitation of the good genetic material
      found. Three EAs based on the HFC principle are tested - two on the even-10
      parity genetic programming benchmark problem and a real-world analog circuit
      synthesis problem, and another on the HIFF genetic algorithm (GA) benchmark
      problem. The significant gain in robustness, scalability and efficiency by HFC,
      with little additional computing effort, and its tolerance of small population
      sizes, demonstrates its effectiveness on these problems and shows promise of its
      potential for improving other existing EAs for difficult problems. A paradigm
      shift from that of most EAs is proposed: rather than trying to escape from local
      optima or delay convergence at a local optimum, HFC allows the emergence of new
      optima continually in a bottom-up manner, maintaining low local selection
      pressure at all fitness levels, while fostering exploitation of high-fitness
      individuals through promotion to higher levels.

PMID- 15969903
TI  - A madness to the methods in cognitive neuroscience?

PMID- 15969905
TI  - Priming of color and position during visual search in unilateral spatial neglect.
AB  - We examined priming of visual search by repeated target location or color in two
      patients with left visual neglect and extinction, following strokes centered on
      the right inferior parietal lobe. Both patients, like the healthy controls we
      tested, showed intact priming, with performance speeded when either the location
      or color of a singleton target was repeated over successive trials in a standard
      search condition (Experiment 1). This was observed both from and to targets on
      the contralesional (left) side. Moreover, priming of search was still observed
      even when a return of fixation back to display-center was required between
      successive trials (Experiment 2). When briefer displays were used (Experiment 3),
      the patients often failed to detect left targets. This situation revealed an
      important dissociation: Whereas location priming only arose from preceding left
      targets that had been consciously detected, color priming (possibly arising
      within the intact ventral stream) did not depend on awareness of the preceding
      target. There was considerable color priming from missed targets. These findings
      demonstrate relatively intact priming of visual search by color and location in
      patients with right parietal damage, and also reveal that location priming may
      differ from color priming in requiring awareness.

PMID- 15969904
TI  - Method matters: an empirical study of impact in cognitive neuroscience.
AB  - A major thrust of cognitive neuroscience is the elucidation of structure-function
      relationships in the human brain. Over the last several years, functional
      neuroimaging has risen in prominence relative to the lesion studies that formed
      the historical core of work in this field. These two methods have different
      strengths and weaknesses. Among these is a crucial difference in the nature of
      evidence each can provide. Lesion studies can provide evidence for necessity
      claims, whereas functional neuroimaging studies do not. We hypothesized that
      lesion studies will continue to have greater scientific impact even as the
      relative proportion of such studies in the cognitive neuroscience literature
      declines. Using methods drawn from systematic literature review, we identified a
      set of original cognitive neuroscience articles that employed either functional
      imaging or lesion techniques, published at one of two time points in the 1990s,
      and assessed the effect of the method used on each article's impact across the
      decade. Functional neuroimaging studies were cited three times more often than
      lesion studies throughout the time span we examined. This effect was in large
      part due to differences in the influence of the journals publishing the two
      methods; functional neuroimaging studies appeared disproportionately more often
      in higher impact journals. There were also differences in the degree to which
      articles using one method cited articles using the other method. Functional
      neuroimaging articles were less likely to include such cross-method citations.

PMID- 15969906
TI  - Anxiety reduction through detachment: subjective, physiological, and neural
      effects.
AB  - The ability to volitionally regulate emotions helps to adapt behavior to changing
      environmental demands and can alleviate subjective distress. We show that a
      cognitive strategy of detachment attenuates subjective and physiological measures
      of anticipatory anxiety for pain and reduces reactivity to receipt of pain
      itself. Using functional magnetic resonance imaging, we locate the potential site
      and source of this modulation of anticipatory anxiety in the medial
      prefrontal/anterior cingulate and anterolateral prefrontal cortex, respectively.

PMID- 15969907
TI  - Brain signatures of meaning access in action word recognition.
AB  - The brain basis of action words may be neuron ensembles binding language- and
      action-related information that are dispersed over both language- and action
      related cortical areas. This predicts fast spreading of neuronal activity from
      language areas to specific sensorimotor areas when action words semantically
      related to different parts of the body are being perceived. To test this, fast
      neurophysiological imaging was applied to reveal spatiotemporal activity patterns
      elicited by words with different action-related meaning. Spoken words referring
      to actions involving the face or leg were presented while subjects engaged in a
      distraction task and their brain activity was recorded using high-density
      magnetoencephalography. Shortly after the words could be recognized as unique
      lexical items, objective source localization using minimum norm current estimates
      revealed activation in superior temporal (130 msec) and inferior frontocentral
      areas (142-146 msec). Face-word stimuli activated inferior frontocentral areas
      more strongly than leg words, whereas the reverse was found at superior central
      sites (170 msec), thus reflecting the cortical somatotopy of motor actions
      signified by the words. Significant correlations were found between local source
      strengths in the frontocentral cortex calculated for all participants and their
      semantic ratings of the stimulus words, thus further establishing a close
      relationship between word meaning access and neurophysiology. These results show
      that meaning access in action word recognition is an early automatic process ref
      lected by spatiotemporal signatures of word-evoked activity. Word-related
      distributed neuronal assemblies with specific cortical topographies can explain
      the observed spatiotemporal dynamics reflecting word meaning access.

PMID- 15969908
TI  - Microstimulation of the dorsolateral prefrontal cortex biases saccade target
      selection.
AB  - A long-standing issue concerning the executive function of the primate
      dorsolateral prefrontal cortex is how the activity of prefrontal neurons is
      linked to behavioral response selection. To establish a functional relationship
      between prefrontal memory fields and saccade target selection, we trained three
      macaque monkeys to make saccades to the remembered location of a visual cue in a
      delayed spatial match-to-sample saccade task. We electrically stimulated sites in
      the prefrontal cortex with subthreshold currents during the delay epoch while
      monkeys performed this task. Our results show that the artificially injected
      signal interacts with the neural activity responsible for target selection,
      biasing saccade choices either towards the receptive/movement field (RF/MF) or
      away from the RF/MF, depending on the stimulation site. These findings might
      reflect a functional link between prefrontal signals responsible for the
      selection bias by modulating the balance between excitation and inhibition in the
      competitive interactions underlying behavioral selection.

PMID- 15969909
TI  - Unconscious detection of implicit expectancies.
AB  - The detection of unexpected events is a fundamental process of learning. Theories
      of cognitive control and previous imaging results indicate a prominent role of
      the prefrontal cortex in the evaluation of the congruency between expected and
      actual outcome. In most cases, this attributed function is based on results where
      the person is consciously aware of the discrepancy. In this functional magnetic
      imaging (fMRI) study, we examined violations of predicted outcomes that did not
      enter conscious awareness. Two groups were trained with nearly identical material
      and the effects of new stimuli were assessed after learning. For the first group,
      the material was arranged with a hidden regularity. In this incidental learning
      situation, volunteers acquired implicit knowledge about structural response
      regularities as was demonstrated by an increase in reaction time when introducing
      new stimuli that violated the learned relations. To differentiate the detection
      process of stimuli that deviate from learned expectations from more unspecific
      effects generated by novel, unfamiliar stimuli, the second group was trained with
      rearranged material without a hidden regularity. No behavioral effects were found
      for the introduction of new stimuli in the group without implicit learning.
      Comparing the two groups, specific fMRI effects concerning the violation of
      implicitly learned expectations were found in the ventral prefrontal cortex and
      in the medialtemporal lobe. In accord with theories of learning, the results show
      a direct influence of the detection of prediction errors on the neuronal activity
      in learning related structures even in the absence of conscious knowledge about
      the predictions or their violations.

PMID- 15969910
TI  - Covert speech arrest induced by rTMS over both motor and nonmotor left hemisphere
      frontal sites.
AB  - Blocking the capacity to speak aloud (overt speech arrest, SA) may be induced by
      repetitive transcranial magnetic stimulation (rTMS). The possibility, however, of
      blocking internal speech (covert SA) has not been explored. To investigate this
      issue, we conducted two rTMS experiments. In the first experiment, we stimulated
      two left frontal lobe sites. The first was a motor site (left posterior site) and
      the second was a nonmotor site located in correspondence to the posterior part of
      the inferior frontal gyrus (IFG) (left anterior site). The corresponding right
      hemisphere nonmotor SA site was stimulated as a control. In the second
      experiment, we focused on the right hemisphere and stimulated a right hemisphere
      motor site (right posterior site), and, as control sites, a right hemisphere
      nonmotor site corresponding to the IFG (right anterior site) and a left
      hemisphere anteromedial site (left control). For both experiments, participants
      performed a syllable counting task both covertly and overtly for each stimulation
      site. Longer latencies in this task imply the occurrence of an overt and/or
      covert SA. All participants showed significantly longer latencies when
      stimulation was either over the left posterior or the left anterior site, as
      compared with the right hemisphere site (Experiment 1). This result was observed
      for the overt and covert speech task alike. During stimulation of the posterior
      right hemisphere site, a dissociation for overt and covert speech was observed.
      An overt SA was observed but there was no evidence for a covert SA (Experiment
      2). Taken together, the results show that rTMS can induce a covert SA when
      applied to areas over the brain that are pertinent to language. Furthermore, both
      the left posterior/motor site and the left anterior/IFG site appear to be
      essential to language elaboration even when motor output is not required.

PMID- 15969911
TI  - Reading fluent speech from talking faces: typical brain networks and individual
      differences.
AB  - Listeners are able to extract important linguistic information by viewing the
      talker's face-a process known as ''speechreading.'' Previous studies of
      speechreading present small closed sets of simple words and their results
      indicate that visual speech processing engages a wide network of brain regions in
      the temporal, frontal, and parietal lobes that are likely to underlie multiple
      stages of the receptive language system. The present study further explored this
      network in a large group of subjects by presenting naturally spoken sentences
      which tap the richer complexities of visual speech processing. Four different
      baselines (blank screen, static face, nonlinguistic facial gurning, and auditory
      speech) enabled us to determine the hierarchy of neural processing involved in
      speechreading and to test the claim that visual input reliably accesses sound
      based representations in the auditory cortex. In contrast to passively viewing a
      blank screen, the static-face condition evoked activation bilaterally across the
      border of the fusiform gyrus and cerebellum, and in the medial superior frontal
      gyrus and left precentral gyrus (p < .05, whole brain corrected). With the static
      face as baseline, the gurning face evoked bilateral activation in the motion
      sensitive region of the occipital cortex, whereas visual speech additionally
      engaged the middle temporal gyrus, inferior and middle frontal gyri, and the
      inferior parietal lobe, particularly in the left hemisphere. These latter regions
      are implicated in lexical stages of spoken language processing. Although auditory
      speech generated extensive bilateral activation across both superior and middle
      temporal gyri, the group-averaged pattern of speechreading activation failed to
      include any auditory regions along the superior temporal gyrus, suggesting that f
      luent visual speech does not always involve sound-based coding of the visual
      input. An important finding from the individual subject analyses was that
      activation in the superior temporal gyrus did reach significance (p < .001, small
      volume corrected) for a subset of the group. Moreover, the extent of the left
      sided superior temporal gyrus activity was strongly correlated with speechreading
      performance. Skilled speechreading was also associated with activations and
      deactivations in other brain regions, suggesting that individual differences ref
      lect the efficiency of a circuit linking sensory, perceptual, memory, cognitive,
      and linguistic processes rather than the operation of a single component process.

PMID- 15969912
TI  - Subliminal convergence of Kanji and Kana words: further evidence for functional
      parcellation of the posterior temporal cortex in visual word perception.
AB  - Recent evidence has suggested that the human occipitotemporal region comprises
      several subregions, each sensitive to a distinct processing level of visual
      words. To further explore the functional architecture of visual word recognition,
      we employed a subliminal priming method with functional magnetic resonance
      imaging (fMRI) during semantic judgments of words presented in two different
      Japanese scripts, Kanji and Kana. Each target word was preceded by a subliminal
      presentation of either the same or a different word, and in the same or a
      different script. Behaviorally, word repetition produced significant priming
      regardless of whether the words were presented in the same or different script.
      At the neural level, this cross-script priming was associated with repetition
      suppression in the left inferior temporal cortex anterior and dorsal to the
      visual word form area hypothesized for alphabetical writing systems, suggesting
      that cross-script convergence occurred at a semantic level. fMRI also evidenced a
      shared visual occipito-temporal activation for words in the two scripts, with
      slightly more mesial and right-predominant activation for Kanji and with greater
      occipital activation for Kana. These results thus allow us to separate script
      specific and script-independent regions in the posterior temporal lobe, while
      demonstrating that both can be activated subliminally.

PMID- 15969913
TI  - Neural-cardiac coupling in threat-evoked anxiety.
AB  - Anxiety is a debilitating symptom of many psychiatric disorders including
      generalized anxiety disorder, mood disorders, schizophrenia, and autism. Anxiety
      involves changes in both central and peripheral biology, yet extant functional
      imaging studies have focused exclusively on the brain. Here we show, using
      functional brain and cardiac imaging in sequential brain and cardiac magnetic
      resonance imaging (MRI) sessions in response to cues that predict either threat
      (a possible shock) or safety (no possibility of shock), that MR signal change in
      the amygdala and the prefrontal and insula cortices predicts cardiac
      contractility to the threat of shock. Participants with greater MR signal change
      in these regions show increased cardiac contractility to the threat versus safety
      condition, a measure of the sympathetic nervous system contribution to the
      myocardium. These findings demonstrate robust neural-cardiac coupling during
      induced anxiety and indicate that individuals with greater activation in brain
      regions identified with aversive emotion show larger magnitude cardiac
      contractility increases to threat.

PMID- 15969914
TI  - How close are we to understanding v1?
AB  - A wide variety of papers have reviewed what is known about the function of
      primary visual cortex. In this review, rather than stating what is known, we
      attempt to estimate how much is still unknown about V1 function. In particular,
      we identify five problems with the current view of V1 that stem largely from
      experimental and theoretical biases, in addition to the contributions of
      nonlinearities in the cortex that are not well understood. Our purpose is to open
      the door to new theories, a number of which we describe, along with some
      proposals for testing them.

PMID- 15969915
TI  - Movement generation with circuits of spiking neurons.
AB  - How can complex movements that take hundreds of milliseconds be generated by
      stereotypical neural microcircuits consisting of spiking neurons with a much
      faster dynamics? We show that linear readouts from generic neural microcircuit
      models can be trained to generate basic arm movements. Such movement generation
      is independent of the arm model used and the type of feedback that the circuit
      receives. We demonstrate this by considering two different models of a two
      jointed arm, a standard model from robotics and a standard model from biology,
      that each generates different kinds of feedback. Feedback that arrives with
      biologically realistic delays of 50 to 280 ms turns out to give rise to the best
      performance. If a feedback with such desirable delay is not available, the neural
      microcircuit model also achieves good performance if it uses internally generated
      estimates of such feedback. Existing methods for movement generation in robotics
      that take the particular dynamics of sensors and actuators into account
      (embodiment of motor systems) are taken one step further with this approach,
      which provides methods for also using the embodiment of motion generation
      circuitry, that is, the inherent dynamics and spatial structure of neural
      circuits, for the generation of movement.

PMID- 15969916
TI  - Cognitive enhancement mediated through postsynaptic actions of norepinephrine on
      ongoing cortical activity.
AB  - We propose two distinct types of norepinephrine (NE)-neuromodulatory systems: an
      enhanced-excitatory and enhanced-inhibitory (E-E/E-I) system and a depressed
      excitatory and enhanced-inhibitory (D-E/E-I) system. In both systems, inhibitory
      synaptic efficacies are enhanced, but excitatory ones are modified in a
      contradictory manner: the E-E/E-I system enhances excitatory synaptic efficacies,
      whereas the D-E/E-I system depresses them. The E-E/E-I and D-E/E-I systems
      altered the dynamic property of ongoing (background) neuronal activity and
      greatly influenced the cognitive performance (S/N ratio) of a cortical neural
      network. The E-E/E-I system effectively enhanced S/N ratio for weaker stimuli
      with lower doses of NE, whereas the D-E/E-I system enhanced stronger stimuli with
      higher doses of NE. The neural network effectively responded to weaker stimuli if
      brief gamma-bursts were involved in ongoing neuronal activity that is controlled
      under the E-E/E-I neuromodulatory system. If the E-E/E-I and the D-E/E-I systems
      interact within the neural network, depressed neurons whose activity is depressed
      by NE application have bimodal property. That is, S/N ratio can be enhanced not
      only for stronger stimuli as its original property but also for weaker stimuli,
      for which coincidental neuronal firings among enhanced neurons whose activity is
      enhanced by NE application are essential. We suggest that the recruitment of the
      depressed neurons for the detection of weaker (subthreshold) stimuli might be
      advantageous for the brain to cope with a variety of sensory stimuli.

PMID- 15969917
TI  - Advancing the boundaries of high-connectivity network simulation with distributed
      computing.
AB  - The availability of efficient and reliable simulation tools is one of the mission
      critical technologies in the fast-moving field of computational neuroscience.
      Research indicates that higher brain functions emerge from large and complex
      cortical networks and their interactions. The large number of elements (neurons)
      combined with the high connectivity (synapses) of the biological network and the
      specific type of interactions impose severe constraints on the explorable system
      size that previously have been hard to overcome. Here we present a collection of
      new techniques combined to a coherent simulation tool removing the fundamental
      obstacle in the computational study of biological neural networks: the enormous
      number of synaptic contacts per neuron. Distributing an individual simulation
      over multiple computers enables the investigation of networks orders of magnitude
      larger than previously possible. The software scales excellently on a wide range
      of tested hardware, so it can be used in an interactive and iterative fashion for
      the development of ideas, and results can be produced quickly even for very large
      networks. In contrast to earlier approaches, a wide class of neuron models and
      synaptic dynamics can be represented.

PMID- 15969918
TI  - Dynamical analysis of continuous higher-order hopfield networks for combinatorial
      optimization.
AB  - In this letter, the ability of higher-order Hopfield networks to solve
      combinatorial optimization problems is assessed by means of a rigorous analysis
      of their properties. The stability of the continuous network is almost completely
      clarified: (1) hyperbolic interior equilibria, which are unfeasible, are
      unstable; (2) the state cannot escape from the unitary hypercube; and (3) a
      Lyapunov function exists. Numerical methods used to implement the continuous
      equation on a computer should be designed with the aim of preserving these
      favorable properties. The case of nonhyperbolic fixed points, which occur when
      the Hessian of the target function is the null matrix, requires further study. We
      prove that these nonhyperbolic interior fixed points are unstable in networks
      with three neurons and order two. The conjecture that interior equilibria are
      unstable in the general case is left open.

PMID- 15969919
TI  - Some generalized sufficient convergence criteria for nonlinear continuous neural
      networks.
AB  - A reason for applying the direct method of Lyapunov to artificial neural networks
      (ANNs) is to design dynamical neural networks so that they exhibit global
      asymptotic stability. Lyapunov functions that frequently appear in the ANN
      literature include the quadratic function, the Persidskii function, and the Lure
      Postnikov function. This contribution revisits the quadratic function and shows
      that via Krasovskii-like stability criteria, it is possible to have a very simple
      and systematic procedure to obtain not only new and generalized results but also
      well-known sufficient conditions for convergence established recently by non
      Lyapunov methods, such as the matrix measure and nonlinear measure.

PMID- 15969920
TI  - Estimation and marginalization using the Kikuchi approximation methods.
AB  - In this letter, we examine a general method of approximation, known as the
      Kikuchi approximation method, for finding the marginals of a product
      distribution, as well as the corresponding partition function. The Kikuchi
      approximation method defines a certain constrained optimization problem, called
      the Kikuchi problem, and treats its stationary points as approximations to the
      desired marginals. We show how to associate a graph to any Kikuchi problem and
      describe a class of local message-passing algorithms along the edges of any such
      graph, which attempt to find the solutions to the problem. Implementation of
      these algorithms on graphs with fewer edges requires fewer operations in each
      iteration. We therefore characterize minimal graphs for a Kikuchi problem, which
      are those with the minimum number of edges. We show with empirical results that
      these simpler algorithms often offer significant savings in computational
      complexity, without suffering a loss in the convergence rate. We give conditions
      for the convexity of a given Kikuchi problem and the exactness of the
      approximations in terms of the loops of the minimal graph. More precisely, we
      show that if the minimal graph is cycle free, then the Kikuchi approximation
      method is exact, and the converse is also true generically. Together with the
      fact that in the cycle-free case, the iterative algorithms are equivalent to the
      well-known belief propagation algorithm, our results imply that, generically, the
      Kikuchi approximation method can be exact if and only if traditional junction
      tree methods could also solve the problem exactly.

PMID- 15969921
TI  - Bridging the gap: ageing, pharmacokinetics and pharmacodynamics.
AB  - Changes in pharmacokinetics and pharmacodynamics in elderly patients generally
      result in an increase in the incidence of drug toxicity and adverse drug
      reactions. Molecular alterations associated with ageing could bring about
      biological changes, a consequence of which is an altered response to
      pharmacological agents. Unfortunately, research in this area has yet to progress
      beyond the cataloguing of the pharmacokinetic and pharmacodynamic changes
      observed in the elderly. Therefore, real progress in our understanding of
      pharmacogerontology could be achieved if it were possible to merge
      pharmacokinetic and pharmacodynamic studies with recent advances in our
      understanding of the causal processes bringing about ageing changes at the
      cellular level. Therefore, this review will focus on the mechanisms of ageing in
      the hope that the information will be of value to those planning independent
      studies.

PMID- 15969922
TI  - Effect of chitosan on the intranasal absorption of salmon calcitonin in sheep.
AB  - The effects of a chitosan-based delivery system on the pharmacokinetics of
      intranasally administered salmon calcitonin (sCT) were investigated in a sheep
      model. In particular, the feasibility of producing a formulation with a
      comparable or improved bioavailability and/or less variability than the currently
      marketed nasal product (Miacalcin nasal spray, Novartis Pharmaceuticals) was
      assessed. A comparator (control) formulation comprising sCT solution was also
      tested. Sheep (n=6) were dosed intranasally according to a randomized crossover
      design. The intranasal sCT dose was 1100 IU (equivalent to approximately 17 IU kg
      1). After completion of the nasal dosing legs, five of the sheep received 300 IU
      sCT (equivalent to approximately 5 IU kg-1) by subcutaneous injection to estimate
      relative bioavailability. After intranasal or subcutaneous dosing, serial blood
      samples were taken and plasma separated by centrifugation before measuring sCT
      concentrations by ELISA. Pharmacokinetic (non-compartmental) and statistical
      (analysis of variance or non-parametric alternative) analyses were performed. No
      systemic or local adverse effects were observed following intranasal or
      subcutaneous administration of sCT. The mean relative bioavailability of sCT from
      the chitosan solution was improved twofold compared with Miacalcin nasal spray
      and threefold compared with sCT control solution. Inter-animal variability in sCT
      absorption appeared to be lower with use of the chitosan-based solution compared
      with the control solution or commercial product. Based on the reported sheep
      data, a chitosan delivery system could offer the potential to significantly
      improve the intranasal absorption of sCT and reduce the variability in
      absorption. In the clinical setting, this may allow relatively lower doses of the
      drug to be given intranasally and/or lead to improvements in the efficacy or
      quality of intranasal therapy.

PMID- 15969923
TI  - Interaction of water with different cellulose ethers: a Raman spectroscopy and
      environmental scanning electron microscopy study.
AB  - Different non-ionic cellulose ethers like methyl cellulose (MC), hydroxypropyl
      cellulose (HPC) and hydroxypropylmethyl cellulose (HPMC) were investigated. The
      characterization of the cellulose ethers was carried out by thermogravimetry and
      sorption/desorption isotherms. Differences in the properties of the cellulose
      ether films were described by time-dependent contact angle measurements. Changes
      in molecular structure of the raw materials, gels and films caused by water
      contact were studied using Raman spectroscopy. Differences between the
      substitution types and changes due to the gel or film formation were observed. An
      environmental scanning electron microscopy (ESEM) technique was used to
      distinguish the morphological behaviour of the cellulose ether films in contact
      with water. Based on in-situ ESEM experiments, the swelling and drying behaviour
      of the various stages of cellulose ether films (film-hydrated film-dried film)
      were quantified by using image analysis.

PMID- 15969924
TI  - The effect of freeze-drying with different cryoprotectants and gamma-irradiation
      sterilization on the characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide
      glycolide) nanoparticles.
AB  - In the present study, the influence of freeze-drying with several cryoprotective
      agents and gamma (gamma)-irradiation sterilization on the physicochemical
      characteristics of ciprofloxacin HCl-loaded poly(D,L-lactide-co-glycolide) (PLGA)
      nanoparticles was evaluated. Nanoparticles were prepared by W/O/W emulsification
      solvent evaporation followed by high-pressure homogenization. They were freeze
      dried in the presence of 5.0% (w/v) mannitol, trehalose or glucose, with 5.0%
      (w/v) or 15.0% (w/v) dextran as cryoprotectants. The nanoparticles were
      irradiated at a dose of 25 kGy using a 60Co source. The following physicochemical
      properties of the formulations were investigated: the ratio of particle size
      before (initial) and after freeze-drying, the ease of reconstitution of the
      nanoparticle suspensions and the drug-release profiles of irradiated and non
      irradiated nanoparticles. The antibacterial activity against Pseudomonas
      aeruginosa was measured. The freeze-drying process induced a significant increase
      in particle size when no cryoprotectant was employed. Similar results were
      observed when cryoprotectants were added to the formulation. Only when mannitol
      was used was no significant size increase measured. Moreover, for formulations
      with dextran, reconstitution after freeze-drying was difficult by manual
      agitation and particle size could not be determined because of aggregation. After
      gamma-sterilization no significant difference in mean particle size was observed,
      but reconstitution was more difficult and drug release was influenced negatively.
      Ciprofloxacin HCl incorporated in the nanoparticles was still effective against
      the micro-organism selected after freeze-drying and gamma-sterilization.

PMID- 15969925
TI  - Site-specific delivery of anti-inflammatory drugs in the gastrointestinal tract:
      an in-vitro release model.
AB  - Mesalazine and budesonide are anti-inflammatory drugs that are used to induce and
      maintain remission of inflammatory bowel diseases (IBD), such as Crohn's disease
      and ulcerative colitis. Both drug substances are intended to act locally at the
      inflamed sites of the gastrointestinal tract. The therapeutic objective for per
      oral treatment with these drugs is to achieve a high concentration of the active
      drug at the sites of inflammation while minimizing systemic absorption. The aim
      of this study was to develop a test system able to reflect the changing
      environment that a dosage form incorporating the anti-inflammatory agent is
      exposed to as it moves through the gastrointestinal tract. The USP dissolution
      apparatus 3 was used for all experiments. Compendial, as well as biorelevant,
      media were used to simulate passage through the gastrointestinal tract under
      various physiological conditions. Different dosage forms of mesalazine (5
      aminosalicylic acid, 5-ASA) and budesonide available on the German market were
      tested. Although all dosage forms were indicated for the same therapeutic
      objectives, each of the dosage forms exhibited a characteristic release pattern
      under in-vitro conditions simulating a passage through the fasted-state
      gastrointestinal tract. Results from this test series indicate that, in the case
      of various dosage forms of mesalazine and budesonide used for the therapy of
      Crohn's disease and ulcerative colitis, release patterns as the dosage form moves
      through the gastrointestinal tract may vary widely. As the various phenotypes of
      IBD have different requirements in terms of pattern of distribution of the
      inflamed sites, and because other aspects of gastrointestinal physiology vary
      within the patient population, the test methods and approach described here
      should be very useful in designing therapy tailored to the needs of each
      individual patient.

PMID- 15969926
TI  - Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents.
AB  - Quaternary ammonium surfactants, such as benzalkonium chloride and
      cetylpyridinium chloride, are commonly used as antibacterial agents for
      disinfectants and for general environmental sanitation, as well as in
      surfactants, penetration enhancers and preservatives in pharmaceutical and
      cosmetic formulations. However, these agents are known to cause various side
      effects and toxic reactions that are believed to be associated with their
      chemical stability. Soft analogues of the long-chain quaternary ammonium
      compounds were synthesized according to the soft drug approach and their
      physicochemical properties investigated, such as their hydrolytic rate constant,
      surface activity and lipophilicity. Structure-activity studies showed that the
      antimicrobial activity of the compounds was strongly influenced by their
      lipophilicity and chemical stability, the activity increasing with increasing
      lipophilicity and stability. However, in soft drug design structure-activity
      relationships are combined with structure-inactivation relationships during the
      lead optimization. The safety index (SI) of compounds was defined as the
      hydrolytic rate constant divided by the minimum inhibitory concentration. The SI
      of the soft antibacterial agents was found to increase with increasing
      lipophilicity but optimum SI was obtained when their hydrolytic t1/2, at pH 6 and
      60 degrees C, was about 11 h. Optimization of the soft antibacterial agents
      through SI optimization resulted in potent but chemically unstable quaternary
      ammonium antibacterial agents.

PMID- 15969927
TI  - Immuno-stimulating complexes prepared by ethanol injection.
AB  - This study describes the formulation of immuno-stimulating complexes (ISCOMs)
      utilising the ethanol injection technique. Cholesterol and phosphatidylcholine
      were dissolved in ethanol and the resulting solution was rapidly injected into a
      stirred, aqueous solution of the triterpene-saponin mixture Quil-A. The reversed
      experiment was also carried out by adding the aqueous Quil-A solution to a
      solution of cholesterol/phosphatidylcholine dissolved in ethanol. This was done
      by either rapid injection or dropwise addition of the aqueous Quil-A solution.
      The colloidal dispersions obtained by ethanol injection and reversed addition
      were compared with formulations obtained by the dialysis and lipid-film hydration
      methods. In a further experiment, the preparation of ISCOMs from liposomes as
      precursor structures was investigated. Transmission electron microscopy was used
      to analyse the resulting colloidal dispersions. Samples were also compared with
      respect to homogeneity of obtained particle species. The ethanol injection
      technique led to formation of ISCOMs in high numbers within 2 h post formulation.
      The reversed rapid injection resulted in a similar colloidal dispersion,
      differing from the former mainly due to the presence of some helical micellar
      structures. The reversed, dropwise addition led to the formation of helices as
      the predominant colloidal structure. Of the three previously established methods,
      only dialysis led to the formation of ISCOMs within 48 h. The lipid-film
      hydration method and the approach using liposomes as precursor structures did not
      produce ISCOMs under the conditions and within the time periods investigated.
      However, it is known that dispersions prepared by the hydration method
      equilibrate towards ISCOMs after longer storage. Ethanol injection and reversed
      rapid injection are simple, cost-effective and quick methods to produce ISCOMs.

PMID- 15969928
TI  - The influence of Surelease and sodium alginate on the in-vitro release of
      tamsulosin hydrochloride in pellet dosage form.
AB  - The objective of this study was to prepare controlled-release pellets containing
      0.2 mg tamsulosin hydrochloride using a pelletizer-equipped piston extruder and
      double-arm counter-rotating rollers with Surelease and sodium alginate. The
      release of tamsulosin HCl from pellets coated with the commercial aqueous
      ethylcellulose dispersion (Surelease) was investigated at different coating
      loads. In addition, the effect of sodium alginate on drug release was
      investigated by varying the ratio of sodium alginate to microcrystalline
      cellulose (MCC). Dissolution studies were first performed in 500 mL simulated
      gastric fluid (pH 1.2) containing 0.003% (w/w) polysorbate 80 and then in
      simulated intestinal fluids (pH 7.2). The morphology of pellet surfaces and cross
      sections were examined by scanning electron microscopy (SEM). Apparently, the
      spherical pellets were prepared using a pelletizer-equipped piston extruder and
      double-arm counter-rotating rollers. The release profiles of tamsulosin HCl from
      Surelease-coated pellets were significantly affected by changing the content of
      Surelease, the pH of the dissolution medium and the ratio of sodium alginate to
      MCC. The drug release rates not only decreased with increase in the coating load,
      but also increased when the pH of the dissolution medium was increased from 1.2
      to 7.2 regardless of the sodium alginate-to-MCC ratio. Moreover, the drug release
      rate at pH 7.2 was gradually increased by increasing the ratio of sodium alginate
      to MCC. SEM showed smooth surfaces of Surelease-coated pellets. These results
      suggest that Surelease and sodium alginate would be useful excipients in the
      preparation of controlled-release pellets with the desired release profiles.

PMID- 15969929
TI  - Interaction of baicalin and baicalein with antibiotics in the gastrointestinal
      tract.
AB  - To clarify the absorption mechanism of baicalin and to investigate the
      interaction between baicalin and antibiotics, the pharmacokinetics of baicalin
      and its aglycone baicalein in normal rats and in antibiotic-treated (with a
      mixture of neomycin and streptomycin) rats were investigated. A method of liquid
      chromatography-tandem mass spectrometry with a selected reaction monitoring mode
      was used to determine the plasma concentrations of baicalin and baicalein. The
      plasma concentration of total baicalein was determined after treatment of beta
      glucuronidase/sulfatase. Unpaired Student's t-test was used for statistical
      comparison. After oral administration of baicalin, the absolute bioavailability
      of baicalin, based on the AUC of the baicalin parent form, was 2.2+/-0.2% in
      normal rats, which decreased to 1.5+/-0.2% in antibiotic-treated rats. Based on
      the AUC of total baicalein after enzymatic hydrolysis, the absorption of baicalin
      was 28.0+/-5.7%, which significantly decreased to 7.7+/-1.2% in antibiotic
      treated rats. After oral administration of baicalein, the glucuronides/sulfates
      of baicalein were predominant in plasma. Based on the AUC of total baicalein
      after enzymatic hydrolysis, the absorption of baicalein was 36.1+/-4.4% in normal
      rats, which did not differ markedly from that in antibiotic-treated rats
      (P>0.05). The presence of baicalin isomer in plasma after oral administration of
      baicalin indicated that baicalin was transformed, at least in part, to baicalein
      before absorption, then to its conjugated metabolites in rats. Aminoglycosides
      decreased the absorption of baicalin, but not of baicalein, which indicated that
      antibiotics decreased the decomposition of baicalin to baicalein by inhibiting
      intestinal flora, and further influenced the absorption, metabolism and efficacy
      of baicalin. These interactions should be paid attention to in clinical studies
      when baicalin is administered in combination with antibiotics.

PMID- 15969930
TI  - Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols:
      quercetin, kaempferol, and isorhamnetin.
AB  - Quercetin, kaempferol, and isorhamnetin were the most important flavonoid
      constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo
      flavonols were performed in Caco-2 cell mono-layers. Their apparent permeability
      in absorptive and secretion directions was determined, and quercetin, kaempferol
      and isorhamnetin displayed polarized transport, with the Papp,B-A being higher
      than the Papp,A-B (P<0.01 for quercetin, P<0.001 for kaempferol and isorhamnetin,
      Student's t-test). Bcap37/MDR1 cells, which were transfected with a P
      glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or
      isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were
      lower than those in parent cells (P<0.05 for quercetin, P<0.01 for isorhamnetin,
      Mann-Whitney U test). The concentrations of the flavonol in transfected cells
      increased when incubated with the P-gp inhibitor verapamil (P<0.05 for
      kaempferol, Mann-WhitneyU test). A colorometric assay for ATPase activity was
      applied to the detection of interaction of flavonol with P-gp. Quercetin and
      kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase
      activity (P<0.05 for isorhamnetin, Mann Whitney U test). The results indicated
      that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P
      gp. The P-gp type efflux pump might limit the bioavailability of Ginkgo
      flavonols.

PMID- 15969931
TI  - Effect of micafungin on cytochrome P450 3A4 and multidrug resistance protein 1
      activities, and its comparison with azole antifungal drugs.
AB  - The effects of micafungin on cytochrome P450 3A4 (CYP3A4) metabolic and multidrug
      resistance protein 1 (MDR1) transport activities were investigated and compared
      with those of amphotericin B and four azole antifungal drugs (ketoconazole,
      itraconazole, fluconazole and miconazole). The effects on the metabolic activity
      of CYP3A4 were examined by measuring nifedipine oxidase activity in human liver
      microsomes and the effects on MDR1 transport activity were evaluated using
      [3H]digoxin in MDR1-overexpressing LLC-GA5-COL150 cells. An inhibitory effect on
      CYP3A4 activity was found for ketoconazole, itraconazole and miconazole, with 50%
      inhibitory concentrations of 11.7, 32.6 and 74.2 nM, respectively. Fluconazole
      and micafungin had only slight inhibitory effects and amphotericin B had no
      effect. The MDR1-mediated transport of [3H]digoxin was inhibited by ketoconazole
      and itraconazole, and slightly by miconazole. It is suggested that micafungin and
      amphotericin B would be unlikely to cause drug-drug interactions by inhibition of
      CYP3A4 and MDR1. A positive correlation between the inhibitory effects on CYP3A4
      and MDR1 activities was observed, and the physicochemical mechanisms involved and
      impact on clinical treatment should be studied further.

PMID- 15969932
TI  - Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark.
AB  - The chemical composition of the chromatography 63 subfraction (63SF) from the
      ethyl acetate soluble fraction of the crude extract of Croton celtidifolius bark
      presented a high content of total proanthocyanidins (75.0+/-2.3%). HPLC analysis
      of 63SF revealed a dimeric profile (e.g.catechin-(4alpha-->8)-catechin and
      gallocatechin-(4alpha-->8)-catechin) and polymeric proanthocyanidins. In
      pharmacological investigations, 63SF administered intraperitoneally exhibited
      dose-dependent antinociceptive activity against several chemical stimuli,
      including the intraperitoneal injection of acetic acid (ID50 (the dose of 63SF
      which was able to reduce the nociceptive response by 50% relative to the control
      value)=0.9 (0.5-1.6)) and the intraplantar injection of capsaicin (ID50=13.0
      (10.0-17.0)), glutamate (ID50=4.0 (2.0-7.0)) and formalin (ID50 first phase=36.0
      (24.0-53.0) and late phase=11.0 (8.0-14.0)). 63SF administered orally exhibited
      an antinociceptive effect in the formalin test (ID50 first phase=125.0 (89.0
      177.0) and late phase=65.0 (33.0-95.0)). In the same test, 63SF was effective
      when given soon after the first phase, as well as exhibiting therapeutic
      activity. Furthermore, 63SF was effective in models of thermal nociception
      including tail-flick and hot-plate tests. When the mice were treated in the
      neonatal period with capsaicin, the antinociceptive effect of 63SF in the first
      phase of the formalin test was abolished, but pretreatment with naltrexone did
      not change the antinociceptive effect of 63SF. Together, these results provide
      evidence that 63SF exerted a pronounced systemic antinociception against chemical
      (acetic acid, formalin, glutamate and capsaicin tests) and thermal (hot-plate and
      tail-flick tests) nociceptive models of pain in mice at a dose that did not
      interfere with the locomotor activity. The mechanism by which this sub-fraction
      produced antinociception remains unclear, but it is unlikely to involve the
      activation of the opioid system. However, unmyelinated C-fibres sensitive to
      treatment with capsaicin are likely to participate in antinociception caused by
      63SF.

PMID- 15969933
TI  - Green tea polyphenols and dietary fibre protect against kidney damage in rats
      with diabetic nephropathy.
AB  - In this study we examined the effect of green tea polyphenols (GTP) and partially
      hydrolysed guar gum (PHGG) as dietary fibre on diabetic nephropathy, using rats
      that had been subjected to subtotal nephrectomy and injection of streptozotocin.
      The subtotally nephrectomized rats were subjected to resection of three-quarters
      of the kidney. Rats with diabetic nephropathy were divided into four groups:
      untreated controls, and animals that received GTP (100 mg kg-1 body weight day
      1), PHGG (100 mg kg-1 body weight day-1) and GTP plus PHGG (50 mg kg-1 body
      weight day-1 plus 50 mg kg-1 body weight day-1). After 50 days of administration,
      attenuation of urinary protein excretion and the morphological changes peculiar
      to diabetic nephropathy were observed in all three treated groups. Furthermore,
      the group treated with GTP plus PHGG showed an improvement of kidney weight and
      serum levels of urea nitrogen, creatinine and creatinine clearance.
      Hyperglycaemia, as assessed in terms of blood glucose and glycosylated protein
      levels, was also improved by administration of GTP plus PHGG. On the other hand,
      GTP administration increased the activity of superoxide dismutase in the kidney
      to a significant extent. A significant reduction in the total cholesterol
      concentration was also observed in the PHGG-treated group. These results suggest
      that GTP and PHGG could be beneficial as additional therapy in the management of
      diabetic nephropathy.

PMID- 15969934
TI  - Histamine-3 receptor antagonists reduce superoxide anion generation and lipid
      peroxidation in rat brain homogenates.
AB  - Using a cyanide model to induce neurotoxic effects in rat brain homogenates, we
      examined the neuroprotective properties of three H3 antagonists, namely
      clobenpropit, thioperamide and impentamine, and compared them to aspirin, a known
      neuroprotective agent. Superoxide anion levels and malondialdehyde concentration
      were assessed using the nitroblue tetrazolium and lipid peroxidation assays.
      Clobenpropit and thioperamide significantly reduced superoxide anion generation
      and lipid peroxidation. Impentamine reduced lipid peroxidation at all
      concentrations used, but only reduced superoxide anion generation at a
      concentration of 1 mM. In the lipid peroxidation assay, all the drugs compared
      favourably to aspirin. This study demonstrates the potential of these agents to
      be neuroprotective by exerting antioxidant effects.

PMID- 15969935
TI  - Delivery of nebulized budesonide is affected by nebulizer type and breathing
      pattern.
AB  - The aim of this study was to determine the output in-vitro of budesonide from two
      different nebulizers under simulated breathing conditions. The BimboNeb and
      Nebula nebulizers were used to nebulize 2 mL of budesonide (500 microg)
      suspension. Particle size was determined by inertial impaction after a 5-min
      nebulization. Total outputs of the drug from both nebulizers were measured using
      a sinus flow pump to create simulated breathing conditions. Paediatric and adult
      breathing patterns were used, with drug output measured after 5 and 10 min
      nebulization. The mass median aerodynamic diameter of budesonide using the
      BimboNeb (4.5 microm) was significantly greater than that from the Nebula (3.4
      microm) (P<0.01). With the simulated adult breathing pattern, the total drug
      output after 5 min with the BimboNeb (61.5 microg) was twice that from the Nebula
      (30.7 microg). For the paediatric breathing pattern, total outputs were very
      similar for both nebulizers. In all cases, nebulizing for 10 min produced greater
      drug outputs compared with those after 5 min, particularly for the paediatric
      breathing pattern. The amount of aerosolized drug available for inhalation needs
      to be assessed for each nebuliser used and the effect of the patient's breathing
      pattern should also be taken into account.

PMID- 15969936
TI  - Cytotoxic, antiviral (in-vitro and in-vivo), immunomodulatory activity and
      influence on mitotic divisions of three taxol derivatives: 10-deacetyl-baccatin
      III, methyl (N-benzoyl-(2'R,3'S)-3'-phenylisoserinate) and N-benzoyl-(2'R,3'S)-3'
      phenylisoserine.
AB  - The aim of this study was to evaluate cytotoxic, antiviral (in-vitro and in-vivo)
      and immunomodulatory activity, as well as the influence on mitotic division, of
      three taxol derivatives representing modified parts of its molecule: 10-deacetyl
      baccatin III, methyl (N-benzoyl-(2'R,3'S)-3'-phenylisoserinate) and N
      benzoyl(2'R,3'S)-3'-phenylisoserine. The cytotoxicity of the compounds, assessed
      by the formazane method, was relatively low, with a 50% cytotoxic concentration
      (CC50)>500 microg mL-1. Moreover, all tested compounds inhibited Herpes simplex
      type 1 virus (HSV-1) replication in non-cytotoxic concentrations in-vitro.
      Selectivity indices were in the range 9.5-46.7. Anti-HSV-1 activity of the
      compounds may be associated with their influence on mitotic division. All of the
      compounds decreased the number of cell divisions. Mitotic indices ranged from
      40/1000 (4.0%) to 62/1000 (6.2%). One compound, 10-deacetyl-baccatin III,
      influenced the growth of tumours induced in mice by infection with Moloney murine
      sarcoma virus. The effect of the tested compounds on T lymphocyte proliferation
      was evaluated by measurement of the activity of tritiated thymidine incorporated
      into DNA of dividing cells. One compound, methyl (N-benzoyl-(2'R,3'S)-3'
      phenylisoserinate), inhibited T lymphocyte proliferation. This paper demonstrates
      that modified parts of the taxol molecule possess various types of biological
      activity in-vitro and in-vivo. Further experiments, focused on revealing their
      mechanisms of action, are necessary.

PMID- 15969937
TI  - Ecabet sodium raises plasma levels of calcitonin generelated peptide and
      substance P in healthy humans.
AB  - Ecabet sodium (ecabet), a cytoprotective drug, produces an increase in mucosal
      blood flow. One of the gastrointestinal motility regulatory factors has been
      assumed to be the induction of changes in the levels of peptides (gastrin,
      somatostatin and motilin) in plasma. On the other hand, recently,
      capsaicinsensitive afferent nerves were shown to play an important role in
      gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and
      enhances the release of calcitonin gene-related peptide (CGRP) and substance P in
      the stomach. We studied the effect of ecabet on human plasma gastrin-,
      somatostatin-, motilin-, CGRP- and substance P-like immunoreactive substance (IS)
      in healthy subjects. Ecabet sodium at a dose of 3.0 g, or placebo, was orally
      administered in five healthy males. The blood samples were taken before and at
      20, 40, 60, 90, 120, 180 and 240 min after administration, subjected to
      extracting procedures, and submitted to a highly sensitive enzyme immunoassay
      system. Single administration of ecabet caused significant (P<0.05) increases in
      plasma CGRP-, substance P- and somatostatin-IS concentration compared with
      placebo. Ecabet significantly decreased plasma gastrin-IS levels compared with
      placebo. In this study, we hypothesized that ecabet might stimulate capsaicin
      sensitive afferent nerves indirectly and improve mucosal blood flow; this might
      be a key mechanism underlying its gastroprotective action.

PMID- 15969938
TI  - Thermotropic liquid crystalline drugs.
AB  - Crystalline solids are characterized by long-range positional and orientational
      order in three dimensions, whereas amorphous liquids lack long-range order in any
      dimension. Liquid crystals (mesophases) show structural, mechanical and optical
      properties intermediate to those of crystalline solids and the amorphous, liquid
      state of matter. There are two principle types of liquid crystals: thermotropic
      liquid crystals (TLCs) and lyotropic liquid crystals (LLCs). TLCs can be formed
      by heating a crystalline solid or by cooling an isotropic melt of a TLC-forming
      molecule (mesogen). In the first part of this review the types of liquid crystals
      are defined and classified and the structural properties of mesogens are
      explained. In the second part, ten case studies of thermotropic mesomorphous
      drugs and pharmaceutically relevant molecules (arsphenamine, nafoxidine
      hydrochloride, L-660711, palmitoyl propranolol hydrochloride, penbutolol sulfate,
      itraconazole hydrochloride, fenoprofen sodium, fenoprofen calcium, ciclosporin
      and cholesteryl esters) are presented and their thermotropic mesomorphism is
      described. The review closes with a brief discussion of the unusual properties of
      drug mesophases and a potential use of drugs and excipients in this fourth state
      of matter.

PMID- 15969939
TI  - Design and evaluation of compound metformin/glipizide elementary osmotic pump
      tablets.
AB  - A simple elementary osmotic pump (EOP) system that could deliver metformin
      hydrochloride (MT) and glipizide (GZ) simultaneously for extended periods of time
      was developed in order to reduce the problems associated with multidrug therapy
      of type 2 non-insulin-dependent diabetes mellitus. In general, both highly and
      poorly water-soluble drugs are not good candidates for elementary osmotic
      delivery. However, MT is a highly soluble drug with a high dose (500 mg) while GZ
      is a water-insoluble drug with a low dose (5 mg) so it is a great challenge to
      pharmacists to provide satisfactory extended release of MT and GZ. In this paper
      sodium carbonate was used to modulate the solubility of GZ within the core and MT
      was not only one of the active ingredients but also the osmotic agent. The
      optimal EOP was found to deliver both drugs at a rate of approximately zero order
      for up to 10 h in pH 6.8, independent of environment media. In-vivo evaluation
      was performed relative to the equivalent dose of conventional MT tablet and GZ
      tablet by a cross-study in six Beagle dogs. The EOP had a good sustained effect
      in comparison with the conventional product. The prototype design of the system
      could be applied to other combinations of drugs used for cardiovascular diseases,
      diabetes, etc.

PMID- 15969940
TI  - Evaluation of ultrasonic atomization as a new approach to prepare ionically cross
      linked chitosan microparticles.
AB  - Ultrasonic atomization was evaluated as a new approach for the preparation of
      ionically cross-linked controlled-release chitosan microparticles loaded with
      theophylline as the model drug, using tripolyphosphate (TPP) as counter-ion. It
      was possible to nebulize both 2% and 3% (w/v) chitosan solutions as a function of
      their viscosity, usually not processed by employing the conventional nebulizer.
      The results of the chitosan molecular characterization using the SEC-MALS
      analysis revealed that ultrasonic atomization caused a certain depolymerization,
      probably due to the main chain scission of the 1,4-glycosidic bond; however,
      Fourier transform-infrared spectroscopy revealed the absence of other chemical
      modifications. The ultrasonic atomization allowed preparation of TPP cross-linked
      chitosan microparticles mostly ranging between 50 and 200 mum. As regards
      manufacturing parameters, the linking time and washing medium were found to
      affect the properties of the microparticles, while the stirring rate of the TPP
      solution did not show any influence. The evaluation of the formulation variables
      revealed that chitosan concentration strongly affected both the feasibility of
      the ultrasonic atomization and the drug release. All the microparticles showed an
      encapsulation efficiency of > 50 % and, after an initial burst effect, a
      controlled release of drug for 48 h. In conclusion, the ultrasonic atomization
      could be proposed as a robust and innovative single-step procedure with scale-up
      potential to successfully prepare ionically cross-linked chitosan microparticles.

PMID- 15969941
TI  - Comparison of post-emulsification freeze drying or spray drying processes for the
      microencapsulation of plasmid DNA.
AB  - In this work, methods used to microencapsulate plasmid DNA in a biodegradable
      polymer were compared for their effects on the physicochemical characteristics of
      DNA-loaded microparticles and on the release and integrity of encapsulated DNA.
      Microparticles were formulated by either w/o/w emulsification and freeze-drying
      (EFD) or by w/o/w emulsification and spray-drying (ESD). The influence of both
      manufacturing processes on particle morphology, charge, release characteristics
      and biological activity of encapsulated DNA was evaluated. Particles produced by
      emulsification/spray-drying exhibited more diversity in shape and size than those
      produced by emulsification/freeze-drying. These particles also exhibited higher
      plasmid DNA encapsulation efficiency than particles produced by
      emulsification/freeze-drying. The fractional DNA release rates were similar over
      the first 25 days for both formulations, release rate declining more rapidly at
      later times for the ESD product. Mammalian cell transfection assays confirmed the
      biological activity of encapsulated DNA extracted from both types of particles,
      with significantly higher transfection levels being observed for ESD particles.
      Application of a double emulsion (w/o/w) before spray drying resulted in higher
      encapsulation levels (> 90%) relative to previous literature values, which used
      single (w/o) emulsions before spray drying. The emulsification/spray-drying
      technique described here appears to be a rapid and efficient method for the
      preparation of PLGA microparticles loaded with plasmid DNA.

PMID- 15969942
TI  - Design of novel injectable cationic microspheres based on aminated gelatin for
      prolonged insulin action.
AB  - The aim of this study was to prepare two types of injectable cationized
      microspheres based on a native gelatin (NGMS) and aminated gelatin with
      ethylenediamine (CGMS) to prolong the action of insulin. Release of rhodamin B
      isothiocyanate insulin from CGMS was compared with that from NGMS under in-vitro
      and in-vivo conditions. Lower release of insulin from CGMS compared with that
      from NGMS was caused by the suppression of initial release. The disappearance of
      125I-insulin from the injection site after intramuscular administration by NGMS
      and CGMS had a biphasic profile in mice. Almost all the 125I-insulin had
      disappeared from the injection site one day after administration by NGMS. The
      remaining insulin at the injection site after administration by CGMS was
      prolonged, with approximately 59% remaining after one day and 16% after 14 days.
      The disappearance of CGMS from the injection site was lower than that of NGMS.
      However, the difference in these disappearance rates was not great compared with
      those of 125I-insulin from the injection site by NGMS and CGMS. The time course
      of disappearance of 125I-CGMS from the injection site was similar to that of 125I
      insulin by CGMS. The initial hypoglycaemic effect was observed 1 h after
      administration of insulin by NGMS, thereafter its effect rapidly disappeared. The
      hypoglycaemic effect was observed 2-4 h after administration by CGMS and
      continued to be exhibited for 7 days. The prolonged hypoglycaemic action by CGMS
      depended on the time profiles of the disappearance of insulin from muscular
      tissues, which occurs due to the enzymatic degradation of CGMS.

PMID- 15969943
TI  - The sensitivity of the cis/trans-isomerization of enalapril and enalaprilat to
      solvent conditions.
AB  - The cis- and trans-isomers of enalapril and enalaprilat can be resolved by HPLC
      and by capillary electrophoresis. The isomeric content of enalapril is perturbed
      by the ionization of both its carboxyl and amine groups, while the isomeric
      content of enalaprilat is only perturbed by the ionization of its amine group.
      Increasing the hydrophobicity of the analyte solvent, as reflected in its molar
      polarization, increases the Z (cis) content of enalapril and markedly decreases
      the kinetics for isomerization. Far UV circular dichroic measurements suggest
      that the increase in Z (cis) content of enalapril is due to protonation of its
      carboxylate group. Taken together, the in-vitro properties of enalapril and
      enalaprilat suggest that the in-vivo transformation of the prodrug enalapril to
      the inhibitor enalaprilat and its delivery to angiotensin-converting enzyme
      should not be significantly limited by cis/trans-isomerization.

PMID- 15969945
TI  - Comparative study of the disposition of levofloxacin, netilmicin and cefepime in
      the isolated rat lung.
AB  - An experimental model of artificially perfused and mechanically ventilated lung
      has been applied to compare the kinetic behaviour of levofloxacin, cefepime and
      netilmicin in this body tissue. The study has been performed to explore the
      usefulness of the isolated lung technique in the pharmacokinetic field,
      particularly to study the disposition of antibiotics in pulmonary tissue. The
      lung was perfused with Krebs-Henseleit medium containing 3% bovine albumin at a
      flow rate of 5 mL min(-1). It was ventilated at 60 respirations/min with a 2-mL
      tidal volume of air previously humidified and warmed to 37 degrees C. The
      concentrations of the above antibiotics were determined by HPLC techniques and
      the outflow curves were analysed by stochastic, as well as by model-dependent,
      methods. The results show pharmacokinetic differences among these antibiotics,
      which are in accordance with previously reported data, levofloxacin being the
      drug with the highest distribution coefficient in this tissue (1.25 +/- 0.14 vs
      0.39 +/- 0.07 and 0.41 +/- 0.06 mL g(-1) for netilmicin and cefepime,
      respectively). Accordingly, the isolated lung of the rat, under the experimental
      conditions used here, constitutes an alternative model to be incorporated to
      pharmacokinetic studies with a great potential use for those drugs that show a
      pharmacological or toxicological action depending on the kinetic profile in the
      lung tissue.

PMID- 15969944
TI  - Intratracheal budesonide-poly(lactide-co-glycolide) microparticles reduce
      oxidative stress, VEGF expression, and vascular leakage in a benzo(a)pyrene-fed
      mouse model.
AB  - The purpose of this study was to determine whether intratracheally instilled
      polymeric budesonide microparticles could sustain lung budesonide levels for one
      week and inhibit early biochemical changes associated with benzo(a)pyrene (B[a]P)
      feeding in a mouse model for lung tumours. Polymeric microparticles of budesonide
      poly (DL-lactide-co-glycolide) (PLGA 50:50) were prepared using a solvent
      evaporation technique and characterized for their size, morphology, encapsulation
      efficiency, and in-vitro release. The microparticles were administered
      intratracheally (i.t.) to B[a]P-fed A/J mice. At the end of one week drug levels
      in the lung tissue and bronchoalveolar lavage (BAL) were estimated using HPLC and
      compared with systemic (intramuscular) administration. In addition, in-vivo end
      points including malondialdehyde (MDA), glutathione (GSH), total protein levels
      and vascular endothelial growth factor (VEGF) in BAL, and VEGF and c-myc mRNA
      levels in the lung tissue were assessed at the end of one week following
      intratracheal administration of budesonide microparticles. Budesonide-PLGA
      microparticles (1-2 microm), with a budesonide loading efficiency of 69-94%,
      sustained in-vitro budesonide release for over 21 days. Compared with the
      intramuscular route, intratracheally administered budesonide-PLGA microparticles
      resulted in higher budesonide levels in the BAL and lung tissue. In-vivo, B[a]P
      feeding increased BAL MDA, lung VEGF mRNA, lung c-myc mRNA, BAL total protein,
      and BAL VEGF levels by 60, 112, 71, 154, and 78%, respectively, and decreased BAL
      GSH by 62%. Interestingly, intratracheally administered budesonide-PLGA particles
      inhibited these biochemical changes. Thus, biodegradable budesonide
      microparticles sustained budesonide release and reduced MDA accumulation, GSH
      depletion, vascular leakage, and VEGF and c-myc expression in B[a]P-fed mice,
      indicating the potential of locally delivered sustained-release particles for
      inhibiting angiogenic factors in lung cancer.

PMID- 15969946
TI  - ET(B) receptor agonist, IRL 1620, does not affect paclitaxel plasma
      pharmacokinetics in breast tumour bearing rats.
AB  - Endothelins are potent endogenous vasoactive substances. We have found that
      intravenous administration of endothelin (ET)B receptor agonist, IRL 1620 (N-suc
      [Glu9, Ala(11,15)]ET-1 (8-21)) to tumour bearing rats increases blood perfusion
      and enhances delivery of chemotherapeutic agents to the tumour tissue. This study
      was conducted to determine whether IRL 1620, an ET(B) receptor selective agonist,
      alters pharmacokinetics of paclitaxel in breast tumour bearing rats. Breast
      tumours were induced in female Sprague-Dawley rats by N-methyl-n-nitrosourea (50
      mg kg(-1), i.p). Saline (0.3 mL kg(-1), i.v.) or IRL 1620 (3 nmol kg(-1), i.v.),
      was administered to the tumour bearing rats via the tail vein. Paclitaxel (3 mg
      kg(-1), i.v.) was administered 15 min after saline or IRL 1620 injection. Serial
      plasma samples were collected up to 10 h after paclitaxel administration and
      analysed using an HPLC-UV assay. In a similar study [3H]-paclitaxel (40 microCi,
      i.v.) was administered after saline or IRL 1620 injection as described above and
      serial plasma samples were collected until 24 h. Data was fitted to a three
      compartment model and pharmacokinetic parameters were generated using WinNonlin
      software. The AUC(0-infinity) (9.42 +/- 3.18 microg h mL(-1)), clearance (0.69 +/
      0.17 L h(-1) kg(-1)), volume of distribution (10.31 +/- 4.54 L kg(-1)) and half
      life (1.00 +/- 0.32 h) of [3H]-paclitaxel in tumour rats were similar in rats
      treated with IRL 1620 or vehicle. Tumour concentration of [3H]-paclitaxel was
      determined in rats treated with IRL 1620 or vehicle and there was a significant
      increase in tumour paclitaxel concentration (308.59 +/- 24.42%) in rats treated
      with IRL 1620 compared with vehicle. It is concluded that IRL 1620, an ET(B)
      receptor agonist, does not alter paclitaxel pharmacokinetics and can selectively
      augment the delivery of paclitaxel to the tumour tissue.

PMID- 15969947
TI  - 6-Hydroxymelatonin protects against quinolinic-acid-induced oxidative
      neurotoxicity in the rat hippocampus.
AB  - Melatonin, a naturally occurring chemical mediator, although assigned a diverse
      range of functions, has attracted interest because of its ability to function as
      a free radical scavenger. Its major hepatic metabolite and photoproduct, 6
      hydroxymelatonin (6-OHM), also shares this property. Since singlet oxygen and
      quinolinic acid (QUIN) are critically involved in the pathology of neurotoxicity,
      the objective of this study was to investigate the ability of 6-OHM to scavenge
      singlet oxygen and evaluate its ability to scavenge superoxide anions and reduce
      QUIN-induced neurotoxicity in the hippocampus in-vivo. The results show that 6
      OHM is an efficient inhibitor of singlet oxygen formation as indicated by the
      rate constants and quantum yields reported for 6-OHM and zinc phthalocyanine
      (ZnPc), respectively. 6-OHM, appears to reduce QUIN-induced superoxide anion
      generation in the hippocampus, which provides some evidence of the
      neuroprotective effects of 6-OHM.

PMID- 15969948
TI  - Aciclovir protects against quinolinic-acid-induced oxidative neurotoxicity.
AB  - AIDS-related encephalopathy, including AIDS dementia complex (ADC) and the
      opportunistic disease, herpes simplex encephalitis (HSE), are postulated to arise
      due to the release of neurotoxic products, such as quinolinic acid (QUIN), by
      activated microglial cells in the brain. QUIN causes a cascade of events to
      occur, which leads to the production of reactive oxygen species (ROS), these
      being ultimately responsible for oxidative neurotoxicity. The antiherpes
      antiviral aciclovir has been reported to protect against neuron loss in HSE, but
      the mechanism for this neuroprotection is unknown. Therefore, this study was
      conducted to investigate whether aciclovir has the ability to inhibit QUIN
      induced lipid peroxidation in rat brain homogenates, after in-vitro and in-vivo
      exposure to QUIN and aciclovir. The thiobarbituric acid (TBA) assay was the
      method used to analyse lipid peroxidation. Rat brains were also examined
      histologically after in-vivo exposure to visually assess whether neuron loss was
      suppressed. The results show that aciclovir inhibits the QUIN-induced lipid
      peroxidation, in a dose-dependent manner. Furthermore, aciclovir reduced necrosis
      of hippocampal neurons and retained the characteristic morphology, integrity and
      arrangement of these cells. Thus, it appears that aciclovir has neuroprotective
      properties, which could possibly be useful in the treatment of AIDS-related
      encephalopathy.

PMID- 15969949
TI  - Phytostanol tablets reduce human LDL-cholesterol.
AB  - The feasibility of using solid dosage forms containing stanol lecithin to lower
      human LDL-cholesterol was investigated. The particle size distribution of a
      coarse aqueous dispersion of a stanol lecithin mixture was determined at various
      weight ratios of the components. At a stanol-to-lecithin weight ratio of 1.00
      1.50, dispersions could be spray dried and the solid reconstituted with water to
      produce a particle size distribution that was similar to that of the aqueous
      dispersion from which it was derived. Two solid dosage forms containing this
      spray-dried stanol lecithin preparation had different disintegration times-
      tablets less than 10 min and capsules greater than 45 min. Each delivery system
      was then tested for LDL-cholesterol reduction activity in a placebo-controlled,
      double-blind clinical trial containing a total of 52 subjects. After a six-week
      treatment period, the group that received rapidly disintegrating stanol lecithin
      tablets (1.26 g stanols daily) experienced a decrease in both LDL-cholesterol and
      the ratio of LDL-cholesterol to HDL-cholesterol by 10.4% (P = 0.01) and 11.5% (P
      = 0.03), respectively, relative to placebo. On the other hand, with slowly
      disintegrating capsules (1.01 g daily) there was no statistically significant
      difference in any lipid parameter between the active group and placebo group.
      Taken together, these studies demonstrate that for maximum LDL-cholesterol
      reduction activity the stanol lecithin formulation must be delivered in a rapidly
      dispersible form to reach the site of cholesterol absorption.

PMID- 15969950
TI  - In-vitro antiproliferative effects on human tumour cell lines of extracts and
      jacaranone from Senecio leucanthemifolius Poiret.
AB  - We have studied the cytotoxic activity of extracts and jacaranone from Senecio
      leucanthemifolius Poiret. Extracts from S. leucanthemifolius were able to inhibit
      the in-vitro proliferation of a series of human tumour cell lines. The
      dichloromethane extract demonstrated effective cytotoxic activity with an IC50 of
      20.1 microg mL(-1) on the large cell carcinoma cell line COR-L23. The ethyl
      acetate extract showed an IC50 value of 5.0 microg mL(-1) and the butanol extract
      an IC50 value of 6.4 microg mL(-1) on the same cell line. A major active
      constituent of the dichloromethane extract was shown to be jacaranone, which was
      demonstrated to have a very strong activity against all of the tumour cell lines
      with IC50 values between 2.86 and 3.85 microg mL(-1), although it did not account
      for all the activity observed. Constituents of S. leucanthemifolius extracts were
      identified by GC/MS analysis and NMR.

PMID- 15969951
TI  - Effects of phenylethanoid glycosides from Digitalis purpurea L. on the expression
      of inducible nitric oxide synthase.
AB  - We have isolated four different phenylethanoid glycosides (purpureaside A,
      desrhamnosyl acteoside, calceolarioside B and plantainoside D) from the leaves of
      Digitalis purpurea (foxglove). The effects of these glycosides on activator
      protein-1 (AP-1)-mediated inducible nitric oxide synthase (iNOS) gene expression
      in the Raw264.7 macrophage cell line have been studied. Of these four glycosides,
      purpureaside A potently inhibited iNOS induction by lipopolysaccharide (LPS).
      Increase in iNOS mRNA by LPS was completely suppressed by purpureaside A.
      Purpureaside A did not significantly affect LPS-inducible nuclear factor-kappaB
      (NF-kappaB) activation or the nuclear translocation of p65. Moreover, a reporter
      gene assay using AP-1 specific luciferase reporter revealed that the enhanced
      activity of AP-1 by LPS was completely abolished in cells treated with
      purpureaside A. These results demonstrated that purpureaside A inhibited LPS
      inducible iNOS expression in macrophages through the suppression of AP-1, but not
      of NF-kappaB.

PMID- 15969952
TI  - Inhibitory effects of a fermented ginseng extract, BST204, on the expression of
      inducible nitric oxide synthase and nitric oxide production in lipopolysaccharide
      activated murine macrophages.
AB  - In this study, the effects of BST204, a fermented ginseng extract, on the
      expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO)
      production are looked into. Crude ginseng extract was incubated with ginsenoside
      beta-glucosidase to prepare BST204. BST204, unlike lipopolysaccharide (LPS) and
      crude ginseng extract, did not affect the level of iNOS protein and NO production
      in unstimulated RAW 264.7 cells. However, it suppressed the level of iNOS protein
      and NO production in LPS-stimulated RAW 264.7 cells but did not manifest the same
      effect on the iNOS mRNA level. An investigation of the activating phosphorylation
      of p70 S6 kinase and 4E-BP1, which are important for translation, was conducted
      to investigate the suppressive mechanism of iNOS protein. LPS increased the
      phosphorylation of p70 S6 kinase, but not 4E-BP1, in a time-dependent manner, and
      BST204 inhibited it in a dose-dependent manner. The expression of iNOS protein,
      however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6
      kinase. Therefore, this paper suggests that the suppression of iNOS protein by
      BST204 was partially correlated with the inhibition of p70 S6 kinase activation.

PMID- 15969953
TI  - Anti-inflammatory and antimicrobial effect of lectin from Lonchocarpus sericeus
      seeds in an experimental rat model of infectious peritonitis.
AB  - We have investigated the anti-inflammatory and antimicrobial effect of the lectin
      from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in
      adult Wistar rats. Animals were treated with saline or LSL (10 mg kg(-1), i.v)
      immediately and 6 h after the induction of peritonitis via cecal ligation and
      single puncture. Twelve hours after surgery, animals were killed and the
      infectious process was monitored by total and differential count of cells from
      blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram
      and the number of viable bacteria of the peritoneal cavity. LSL treatment
      decreased the inflammatory response evoked by the induction of peritonitis, as
      seen by the inhibition of neutrophil migration into peritoneal cavities,
      leucocytosis and reduction of adenosine deaminase activity in the peritoneal
      fluid. All these effects were reversed by the lectin association to N-acetyl
      glucosamine. LSL in-vitro did not show any antimicrobial action, but promoted a
      marked decrease of the viable bacterial population in peritoneal cavities. In
      conclusion, LSL inhibited the inflammatory response and the bacterial
      colonization of infectious peritonitis in rats.

PMID- 15969972
TI  - The emergence of epidemic dengue fever and dengue hemorrhagic fever in the
      Americas: a case of failed public health policy.

PMID- 15969954
TI  - Pharmacodynamic comparison of pantoprazole enantiomers: inhibition of acid
      related lesions and acid secretion in rats and guinea-pigs.
AB  - Pantoprazole is an irreversible proton pump inhibitor that is administered as a
      racemic mixture clinically. The effects of pantoprazole sodium (PAN.Na)
      enantiomers on acid-related lesions were compared using models of pylorus
      ligation induced ulcer, histamine induced ulcer and reflux oesophagitis in rats
      and guinea-pigs. Compared with (+)-PAN.Na and (+/-)-PAN.Na, (-)-PAN.Na showed
      much stronger inhibitory effects on pylorus ligation induced and histamine
      induced ulcers, but similar effects on reflux oesophagitis. The doses of (-)
      PAN.Na, (+)-PAN.Na and (+/-)-PAN.Na required for 50% inhibition (ID50) of acid
      related lesions were 1.28, 5.03 and 3.40 mg kg(-1) against pylorus ligation
      induced ulcer, 1.20, 4.28 and 3.15 mg kg(-1) against histamine induced ulcer, and
      2.92, 3.56 and 3.70 mg kg(-1) against reflux oesophagitis, respectively. The
      inhibitory effects of PAN.Na enantiomers on basal gastric acid output were
      compared in rats with acute fistula. In contrast to inhibitory rates of 89.3% and
      83.6% on gastric acid output by (-)-PAN.Na and (+/-)-PAN.Na at 1.5 mg kg(-1), (+)
      PAN.Na had an inhibitory rate of only 24.7% at the same dose. The above results
      indicate that (-)-PAN.Na is more potent than (+)-PAN.Na at inhibiting acid
      related lesions owing to its stronger inhibition of acid secretion.

PMID- 15969973
TI  - Dengue in Grenada.
AB  - OBJECTIVES: Dengue fever is endemic in the country of Grenada and is grossly
      underreported as a source of morbidity. The goal of this study was to assess the
      status of dengue fever in a representative community in Grenada. METHODS: Surveys
      were conducted in the Mont Tout/Grand Anse Valley area in the parish of St.
      George's from March to June 1996. The objectives of the survey were to: (1) to
      assess the knowledge, attitudes, and practices (KAP) of residents; (2) to
      determine the presence of larval and adult Aedes aegypti and their potential
      breeding sites; and (3) to identify the seroprevalence of specific immunoglobulin
      G (IgG) dengue antibodies in the local population. RESULTS: Out of the 102
      respondents to the KAP survey, 100 of them (98%) reported never having had dengue
      fever. Of the 75 persons who agreed to have blood samples taken, 70 of them (93%)
      (95% confidence interval = 85.1%-97.8%) tested positive with the IgG enzyme
      linked immunosorbent assay, indicating past exposure. In terms of water storage,
      98 of 102 respondents (96%) stored fresh water in containers. The vector survey
      found 57 of the 102 households (56%) had Ae. aegypti larvae in water containers
      on their property, and 94 of 102 dwellings (92%) had adult Ae. aegypti mosquitoes
      indoors. CONCLUSIONS: Although many people were familiar with dengue fever and
      mosquitoes, the 1996 survey found that their knowledge of the important
      relationships among mosquitoes, human behavior, and disease transmission was
      incomplete. Since 1996, continued education efforts have been made in the public
      school system and with national public health campaigns, yet little effort has
      been specifically targeted towards our study community. These data suggest
      Grenada has a need for continued community education that addresses dengue fever
      transmission and Ae. aegypti reduction.

PMID- 15969974
TI  - [The use of bibliographic databases by Spanish-speaking Latin American biomedical
      researchers: a cross-sectional study].
AB  - OBJECTIVE: To describe how Spanish-speaking biomedical professionals in Latin
      America access and utilize bibliographic databases. METHODS: Based on a MEDLINE
      search, 2 515 articles published between August 2002 and August 2003 were
      identified that dealt with and/or had authors from 16 countries: Argentina,
      Bolivia, Chile, Colombia, Costa Rica, Cuba, Ecuador, Guatemala, Honduras, Mexico,
      Nicaragua, Panama, Paraguay, Peru, Uruguay, and Venezuela. The search was limited
      to references to basic science, clinical science, or social medicine. A survey
      was sent by e-mail to researchers who lived in 15 of the 16 countries (the
      exception being Nicaragua). The survey asked about the researcher's area of work
      (basic science, clinical science, or public health), the level of skill in using
      databases, the frequency and type of access to the databases most utilized, the
      impact from not having access to the full text of articles when preparing a
      manuscript, and how the respondent usually obtained the full-text version of
      articles. RESULTS: A total of 586 e-mail messages with the survey were sent out,
      and 185 responses were received (32%). The databases most utilized to obtain
      biomedical information were MEDLINE (34.1%), general search engines (Google,
      Yahoo!, and AltaVista) (15.9%), on-line journals (9.8%), BIREME-LILACS (6.0%),
      BioMedNet (5.4%), the databases of the Centers for Disease Control and Prevention
      of the United States of America (5.2%), and the Cochrane Library (4.9%). Of the
      respondents, 64% said they had average or advanced abilities in using MEDLINE.
      However, 71% of the respondents did not use or were not aware of the MEDLINE
      Medical Subject Headings (MeSH), a controlled vocabulary established by the
      National Library of Medicine of the United States of America for indexing
      articles. The frequency of accessing the databases was similar in all the
      countries studied, without significant differences in terms of the type of access
      (authorized access to commercial databases, unauthorized access to those
      databases, or access to databases available for free) or the level of abilities.
      Of the respondents, 87% said they had not included important references in the
      articles that they had published because they had not had access to the full text
      of those items, and 56% said they had cited articles that they had not read in
      full. In addition, 7.6% of the respondents admitted to unauthorized use of
      limited-access databases, such as through borrowed passwords or copied disks.
      More than two-thirds of the respondents said they obtained the full text of
      articles through photocopies or directly from the authors. CONCLUSIONS: In order
      to encourage scientific output by Latin American researchers, more of them need
      to be trained in the use of the most frequently used databases, especially
      MEDLINE. Those researchers also need to have expanded access to the biomedical
      literature.

PMID- 15969975
TI  - [Dental waste management in municipal health clinics in Belo Horizonte, Brazil].
AB  - OBJECTIVE: To investigate whether municipal health clinics in the city of Belo
      Horizonte, Brazil, comply with the legal requirements for managing dental wastes.
      METHOD: We collected information from 54 of the city's 105 municipal health
      clinics that provide dental care. At each clinic we interviewed the clinic
      manager, one dental assistant, and one general assistant. Based on the
      requirements outlined in the Belo Horizonte Health Waste Management Manual, we
      assessed characteristics in the following three areas: (1) technical and
      operational (waste classification and characterization, minimization,
      segregation, pretreatment, conditioning, collection and internal and external
      transportation, and external storage); (2) general and organizational
      (inspection, amount of clinic space, environmental permits, floor plan showing
      waste-generating areas, and whether the clinic had a technical specialist
      responsible for managing the health wastes); and (3) human resources (employee
      vaccination records and oversight, occupational safety and occupational medicine
      program, environmental risk prevention program, medical oversight and
      occupational health program, hospital (clinic) infection control committee, and
      training in health waste management). RESULTS: The clinics produced an average of
      270 liters of solid waste per day. None of the clinics surveyed had a plan for
      managing health wastes. The only requirements with which all the clinics complied
      were: segregation of needles and mercury, adequately identified cardboard
      containers used for disposal of cutting and piercing items, and daily internal
      collection and transportation of wastes. CONCLUSIONS: When the risks associated
      with each class of waste have not been established, all the wastes should be
      considered potentially dangerous. Further, a law by itself does not guarantee
      that the public's health will be protected. Before public agencies impose legal
      requirements, it is necessary to know if the agencies themselves are capable of
      enforcing those requirements. Any proposed waste management legislation should be
      based on scientific research.

PMID- 15969976
TI  - Knowledge and attitudes in Puerto Rico concerning dengue prevention.
AB  - OBJECTIVE: Dengue has been endemic in Puerto Rico for three decades. Multiple
      educational and community-based efforts have been developed to inform the
      population about dengue prevention. We undertook this study to understand the
      community members' knowledge, attitudes, and practices related to dengue
      prevention and to elicit their ideas for future prevention campaigns. METHODS: A
      qualitative study based on grounded theory analysis was conducted between
      February and May of 2001. The study involved a total of 34 participants in four
      group interviews who had been identified through the Puerto Rico dengue
      surveillance system. RESULTS: In general, participants had correct knowledge
      about dengue prevention, but they did not associate the mosquitoes inside their
      houses with Aedes aegypti. Participants insisted that "neighbors" needed to
      control larval habitats, and the participants also asked the Government to
      fumigate. CONCLUSIONS: The patterns of knowledge and opinion that emerged in the
      discussions can be arranged along an axis going from high levels of correct
      knowledge to low levels of correct knowledge about dengue and dengue hemorrhagic
      fever and related practices. There were few participants at either extreme. Three
      themes explained these patterns: misconceptions about dengue (based on previously
      delivered information), the "invisibility" of dengue (as compared to other
      diseases), and responsibility (individual and Government). Four strategies for
      preventive behaviors were recommended: developing community groups to identify
      community priorities on prevention, developing volunteer groups to deliver
      prevention messages, making house visits to demonstrate specific control
      measures, and conducting a complementary media campaign to support these
      strategies.

PMID- 15969977
TI  - [Trends in mortality from lung cancer in Mexico, 1980-2000].
AB  - OBJECTIVE: To analyze trends in age-adjusted lung cancer mortality rates in
      Mexico for the period of 1980 through 2000. METHOD: The trends were assessed
      using the adjusted rates of mortality from lung cancer, year of death, year of
      birth, age at death, state, and standard population. The standardized mortality
      rate and the index of potential years of life lost were used to compare incidence
      and premature deaths. The standardized mortality rate was analyzed by age groups
      according to the age at death (30-74 years), five-year observation period (1980
      1999), and birth cohort (1910-1950). Nonparametric Spearman correlations were
      calculated for per capita tobacco consumption, social marginalization, and
      emigration. RESULTS: The adjusted mortality rate from lung cancer declined from
      7.91 per 100 000 in 1989 to 5.96 per 100 000 in 2000. This pattern correlated
      with the reduction in per capita tobacco consumption, from 2.145 kg in 1959 to
      0.451 kg in 1982. The latent period for the appearance of lung cancer in Mexico
      was 30 years. The male:female ratio was 2.4:1. The highest adjusted mortality
      rate was found in men who were 70-74 years old at the time of death. The adjusted
      mortality rates were low among the cohorts of persons born in 1945 or later, and
      those rates declined over the 1980-2000 period. The index of potential years of
      life lost and the incidence of premature death were greater among men. The
      mortality rates for the cohorts of men born between 1915 and 1940 showed a slight
      decline over the 1980-2000 period; beginning with men born in 1944 the rates
      increased slightly, mainly among men 30-34 and 35-39 years old at the time of
      death. For women the adjusted mortality rates were highest among those 75 or
      older; the rates gradually declined among the women born between 1945 and 1960,
      with the largest decrease among women 30-34 years old. The adjusted mortality
      rates varied according to the five-year observation period, the year of death,
      and birth cohort and gender. The correlation coefficient for the adjusted
      mortality rate by state and social marginalization was -0.70 (P = 0.00). There
      was no statistically significant correlation with the index of emigration (P =
      0.56). CONCLUSIONS: Mortality from lung cancer has declined in Mexico. Morbidity
      and premature death due to lung cancer are greater in the states of northern
      Mexico.

PMID- 15969978
TI  - Genetic, dietary, and other lifestyle determinants of serum homocysteine levels
      in young adults in Costa Rica.
AB  - OBJECTIVE: Elevated serum total homocysteine (tHcy) is considered an independent
      risk factor for cardiovascular disease. The objective of this study was to
      develop the first-ever information on the prevalence of hyperhomocysteinemia and
      its determinants in a population in Costa Rica. METHODS: A cross-sectional study
      was conducted to determine serum levels of tHcy, vitamin B(12), folate, and
      creatinine, as well as the presence of the genotype TT for the
      methylenetetrahydrofolate reductase (MTHFR) enzyme. Additionally, dietary vitamin
      intakes and other lifestyle risk factors were assessed. A total of 399 Costa
      Rican adults from the central valley of the country (where the capital city, San
      Jose, is located), aged 20 to 40 years, participated in this study in the year
      2000. Analyses of variance were performed for continuous variables, and the chi
      square test was used for categorical data. Spearman correlation tests were
      calculated to determine associations between variables. Three linear regression
      analyses and one binary logistic model were developed in order to determine the
      predictors for homocysteine levels in the population studied. RESULTS: The
      overall prevalence of hyperhomocysteinemia (>15 micromol/L) in the population was
      6%, 31% of the population were in the range of 10 to 15 micromol/L, 29% had the
      genotype TT for the enzyme MTHFR, 18% presented a vitamin B(12) deficiency (<165
      pmol/L), and none of the persons had low serum folate levels (<7.0 nmol/L). No
      significant associations were found between tHcy and age, smoking, consuming
      alcohol, or dietary vitamin intake. CONCLUSIONS: Only serum vitamin B(12) levels
      and the genotype TT of the enzyme MTHFR were considered significant predictors of
      high serum tHcy levels in the Costa Rica population studied.

PMID- 15969979
TI  - [Dropout from tuberculosis treatment in Nicaragua: the results of a comparative
      study].
AB  - OBJECTIVE: To identify factors related to dropping out from tuberculosis
      treatment in health centers in the departments of Managua and Matagalpa, in
      Nicaragua. METHODS: This study matched cases and controls (1:1 ratio) by age and
      by municipality of treatment. The 251 cases were patients over 15 years of age
      who had dropped out of tuberculosis treatment, and the 251 controls were patients
      who had completed pharmacotherapy, during the period of January 1998 to December
      2001. Data were obtained on demographic and socioeconomic characteristics,
      lifestyle habits, and treatment characteristics. The variables were chosen and
      grouped using a hierarchical theoretical model. Conditional logistic regression
      analysis was used to calculate odds ratios (ORs) with 95% confidence intervals
      (95% CIs). RESULTS: The risk factors for dropping out of tuberculosis drug
      treatment were: male gender (OR, 2.51; 95% CI, 1.63 to 3.94), an unstable living
      situation or being homeless (OR, 3.08; 95% CI, 1.57 to 6.49), changing residence
      during the treatment period (OR, 4.22; 95% CI, 2.06 to 9.93), consuming alcoholic
      beverages (OR, 5.25; 95% CI, 2.43 to 12.94), using illegal drugs (OR, 5.25; 95%
      CI, 2.43 to 12.94), difficulty in access to the health services (OR, 2.64; 95%
      CI, 1.39 to 5.29), and a negative opinion of the health care received (OR, 5.33;
      95% CI, 1.52 to 28.56). CONCLUSIONS: It is essential for the health services in
      Nicaragua to develop measures to reduce the risk of dropout from treatment. In
      particular, it is important for the health sector to work with community groups
      that can support the health sector's activities.

PMID- 15969980
TI  - [How to respond to a dengue epidemic: overview and experience in Puerto Rico].
AB  - Dengue, a viral disease transmitted by mosquitoes, is endemic and frequently
      epidemic in many tropical countries. Because low-incidence periods vary in
      length, it is difficult to know in advance when an epidemic will occur. Response
      efforts, despite being logical, have been counter-productive at times.
      Furthermore, experience has demonstrated that dengue epidemics last a long time,
      making it important that government control efforts be sustainable while they
      last. This article describes priority activities requiring attention in order to
      minimize the impact of dengue epidemics. Such activities, which in many cases can
      be adapted to combat other types of epidemics as well, are as follows: (1)
      establishment of an inter-sectoral action committee, (2) formalization of an
      emergency action plan, (3) epidemiologic surveillance, (4) diagnostic laboratory
      testing, (5) mosquito control, (6) protection of sources of employment and
      special populations, (7) patient care, (8) education of medical personnel, (9)
      research, and (10) transparency before the mass media. The best way to reduce the
      ravaging effects of dengue epidemics is to anticipate their emergence so that
      infection can be prevented and steps can be taken to protect the ill. Relying on
      improvisation to solve all the problems that arise in moments of crisis is
      inefficient and reckless.

PMID- 15969981
TI  - Pregnancy-associated breast cancer.
AB  - PRECIS: Breast masses discovered during pregnancy should receive thorough
      evaluation. Delay in the diagnosis of breast cancer in pregnancy may cause
      increased mortality and should be avoided. As women delay childbearing, the
      incidence of breast cancer during pregnancy may increase. This article aims to
      review the pathophysiology, clinical presentation, and diagnostic and therapeutic
      approach to the pregnant breast cancer patient. In addition, the impact of
      pregnancy on subsequent breast cancer development in high-risk groups, such as
      BRCA1 and BRCA2 mutation carriers and patients with a prior history of breast
      cancer, is discussed. SOURCES AND STUDY SELECTION: We conducted a PubMed search
      using the words breast, cancer, carcinoma, and pregnancy. We also searched for
      abstracts presented at the American Society for Clinical Oncology meetings using
      the words breast cancer and pregnancy. Observational studies were not pooled
      because of the disparity of the data. We reviewed 117 articles and three
      abstracts referring to breast cancer in pregnancy. RESULT: A thorough breast
      examination at the first antenatal visit, before the physiologic changes in
      breast parenchyma obscure a possible mass, is essential. The work-up of masses
      detected during pregnancy should not be postponed until after delivery. Delays in
      diagnosis may contribute to the higher proportion of patients with advanced stage
      at presentation. The prognosis of the pregnant breast cancer patient is similar
      to her stage-matched nonpregnant counterparts in most series. Radiation therapy
      is contraindicated during pregnancy; this limits breast conservation to cases
      presenting during the third trimester. Some chemotherapies can be administered
      during the second and third trimesters. Therapeutic abortion is not necessary,
      although women with high-risk disease may find this preferable. Women with a
      history of breast cancer should be reassured that subsequent pregnancy is not
      known to increase the risk of recurrence. Women with a history of BRCA1/2
      mutations should not be advised that early pregnancy decreases their breast
      cancer risk. CONCLUSIONS: Physicians should aggressively pursue work-up in women
      with a palpable breast mass because early diagnosis may improve the prognosis of
      breast cancer during pregnancy.

PMID- 15969982
TI  - After the smoke clears: environmental and occupational risks for carcinoma of the
      upper aerodigestive tract.
AB  - Both environmental and occupational exposures are associated with the development
      of carcinomas of the upper aerodigestive tract, although most squamous cell
      carcinomas of the upper aerodigestive tract are related to smoking and drinking.
      This review discusses environmental and occupational risk factors, other than
      tobacco and alcohol, for carcinoma of the upper aerodigestive tract and the
      difficulties encountered when attempts are made to study these environmental and
      occupational exposures. However, this is not an all-inclusive review; rather, it
      is designed to give the reader an understanding of the topic, to allow for
      appropriate counseling of patients, and perhaps to advance public health
      initiatives.

PMID- 15969983
TI  - Understanding the role of gender in the incidence of thyroid cancer.

PMID- 15969984
TI  - The risk of bladder, bowel, and sexual dysfunction after radiation therapy: what
      the data tell us and how we can use it to counsel our patients.

PMID- 15969985
TI  - Gemcitabine radiosensitization for rectal cancer: step forward or dance step?

PMID- 15969986
TI  - Induction of thyroid papillary carcinoma cell proliferation by estrogen is
      associated with an altered expression of Bcl-xL.
AB  - PURPOSE: One of the features of thyroid carcinoma is its predilection for women
      of reproductive age relative to men. An increased risk has also been documented
      in women who have used estrogens for gynecologic reasons. The aim of this study
      was to explore the mechanism by which sex hormones contribute to the development
      of thyroid carcinoma, which is not well understood at present. MATERIALS AND
      METHODS: In this study, we investigated the effects of estradiol and testosterone
      on cell proliferation in a human thyroid papillary carcinoma cell line (KAT5) by
      MTT assay. We also studied the expression of estrogen receptors and the levels of
      anti-apoptotic Bcl-xL protein, pro-apoptotic Bax protein, and messenger RNA in
      the cells by Western blot and reverse transcriptase polymerase chain reaction
      analysis. RESULTS: The results showed that estradiol promotes cell proliferation
      when compared with cells treated with testosterone and untreated cells, and that
      the growth-promoting effect of estradiol was attenuated by tamoxifen. The
      expression of Bcl-xL was markedly increased in a dose-dependent manner, resulting
      in an elevated ratio of Bcl-xL to Bax. DISCUSSION: We conclude that estradiol
      promotes KAT5 cell proliferation and that the underlying mechanism may be
      associated with up-regulation of Bcl-xL expression. The data provide insight into
      the molecular mechanism underlying the epidemiologic data that shows a two- to
      threefold increased prevalence of thyroid carcinoma in women relative to men.
      From the therapeutic point of view, the finding that estradiol enhances anti
      apoptotic signaling pathways may be significant in the search for novel
      prevention and treatment strategies of thyroid carcinomas.

PMID- 15969987
TI  - Posttreatment complications of early-stage prostate cancer patients:
      brachytherapy versus three-dimensional conformal radiation therapy.
AB  - PURPOSE: The purpose of this study was to compare treatment complications for
      early-stage prostate cancer managed by either brachytherapy or three-dimensional
      conformal radiotherapy (3D-CRT). MATERIALS AND METHODS: [corrected] Records were
      reviewed for 86 men treated with transperineal interstitial permanent prostate
      brachytherapy and for 76 men treated with dose-escalated (75.6-Gy) six-field
      3DCRT between 1998 and 2000. Median ages were 65 and 66 years, respectively;
      median Gleason scores were 6 and 7; baseline prostate-specific antigen levels
      were 6.1 and 9.0 ng/mL; and the follow-up period was 42 months. In the urinary
      domain, patients who underwent brachytherapy recorded an International Prostate
      Symptom Score prospectively at baseline, as well as 3 months and every 6 months
      following, whereas patients who underwent 3D-CRT were assigned a Radiation
      Therapy Oncology Group (RTOG) late toxicity score at similar time intervals. In
      the bowel domain, RTOG late toxicity score was used for both groups, and
      physician-dictated notes were used to assess sexual function. All patients who
      underwent brachytherapy were prescribed tamsulosin (Flomax) to manage urinary
      symptoms for a minimum of 3 months after treatment. RESULTS: With respect to
      urinary symptoms, a direct comparison cannot be made between the International
      Prostate Symptom Score and the RTOG late toxicity score. Nonetheless, it was
      evident that patients who underwent brachytherapy had more severe urinary
      sequelae in the months after implantation. Tamsulosin was still being used by 78%
      of patients at 6 months, decreasing to 55% at 1 year and 27% at 2 years.
      Intermittent self-catheterization was required at 6 months after treatment by 5%
      of patients who underwent brachytherapy, and a transurethral resection of the
      prostate was performed in one of these patients at 12 months. In patients who
      underwent 3D-CRT, 14% used tamsulosin at some point in the follow-up period and
      none required catheterization or transurethral resection of the prostate. In the
      bowel domain, 20% of patients who underwent brachytherapy experienced grade 1
      gastrointestinal toxicity, most within the first 12 months of follow-up, compared
      with 30% grade 1 or 2 gastrointestinal scores in the 3D-CRT group (peaking in the
      second year after treatment). In the sexual domain, 9% of patients who underwent
      brachytherapy who were previously potent reported a loss of potency by 18 months,
      compared with 53% of patients who underwent 3D-CRT. Without the help of
      sildenafil (Viagra), these figures rose to 24% and 58%. CONCLUSIONS: 3D-CRT is
      associated with fewer urinary symptoms, whereas brachytherapy has a more
      favorable toxicity profile for bowel and sexual function. In the absence of a
      randomized clinical trial, such a comparison can be helpful both in counseling
      patients as to what to expect from either treatment and in facilitating their
      treatment decision process.

PMID- 15969988
TI  - Preoperative concomitant hyperfractionated radiotherapy and gemcitabine for
      locally advanced rectal cancers: a phase I-II trial.
AB  - PURPOSE: The purpose of this study was to determine the maximum tolerated dose of
      gemcitabine when it was administered concomitantly with hyperfractionated
      radiotherapy before surgery in patients with locally advanced rectal cancers and
      to investigate the midterm efficacy of such a regimen. PATIENTS AND METHODS:
      Thirty-seven patients with stage II-III tumors as assessed by computed
      tomography/echoendoscopy were enrolled. Radiotherapy consisted of 50 Gy given in
      two daily fractions of 1.25 Gy over 4 weeks. The starting dose of gemcitabine was
      10 mg/m(2)/day (in a 30-minute i.v. perfusion) twice weekly with planned
      escalation steps of 5 mg/m(2)/day. Surgery was planned at 6 weeks after the end
      of radiotherapy. Main end-points of the study were complete pathological tumor
      response, the rate of clear margin resection, and actuarial locoregional control
      and disease-free survival. The median follow-up for all patients was 32 months
      (range: 10-51 months). RESULTS: At the level of 45 mg/m(2), two of four patients
      presented with dose-limiting rectal toxicities (severe acute proctitis requiring
      hospitalization in the immediate postradiotherapy period). Thus, the gemcitabine
      biweekly dose of 40 mg/m(2) was considered to be the maximum tolerated dose.
      Among the 36 patients who underwent surgery, 17 (47%) had a marked pathological
      response, including six patients (17%) with a microscopically complete response
      and 11 (30%) with only microscopically residual carcinoma of less than 1 cm. All
      of them had clear surgical margins. At 3 years, actuarial overall survival rate
      was 85%, locoregional control was 94.5%, and disease-free survival was 67%.
      DISCUSSION: The present study determined the recommended dose of gemcitabine to
      be 40 mg/m(2) when administered concurrently twice a week with 50 Gy
      hyperfractionated radiotherapy for the preoperative treatment of locally advanced
      rectal cancers. The encouraging pathological response rate and the very low
      locoregional recurrence rate suggest that this innovative approach merits further
      investigation.

PMID- 15969989
TI  - Phase I study of concomitant chemoradiotherapy with irinotecan, 5-FU, and
      hydroxyurea for patients with advanced and/or recurrent head and neck cancer.
AB  - PURPOSE: We sought to investigate CPT-11 as a promising agent to our established
      regimen of 5-fluorouracil (5-FU), hydroxyurea, and hyperfractionated radiation
      therapy. A phase I study was conducted to determine the maximum tolerated dose
      and dose-limiting toxicities of this regimen. PATIENTS AND METHODS: Eligible
      patients included patients with poor prognosis advanced head and neck cancer who
      required radiation therapy. All patients were treated on a 14-day cycle. Each
      patient received 5-FU (600 mg/m(2)/d), hydroxyurea (500 mg orally every 12
      hours), radiation therapy twice daily (150 cGy each fraction), and CPT-11 at a
      starting dose of 5 mg/m(2)/d for 5 consecutive days followed by a 9-day break.
      CPT-11 was escalated in five mg/m(2)/d increments. Dose-limiting toxicity was
      defined as grade 4 hematologic toxicity, persistent grade 4 dermatitis and
      mucositis, grade 4 diarrhea despite maximal pharmacologic intervention, and
      inability to receive full-dose chemotherapy with the next cycle of treatment.
      Fourteen patients were treated at maximum tolerated dose to verify the
      recommended phase II dose. RESULTS: Between August 1998 and August 2001, 31
      patients with advanced and/or recurrent head and neck cancer were enrolled.
      Cohorts of nine, four, three, and 14 patients were treated at 5-, 10-, 15-, and
      10-mg/m(2)/d dose levels of CPT-11. The 5- and 10-mg/m(2)/d dose levels were well
      tolerated All three patients treated at 15 mg/m(2)/d experienced neutropenic dose
      limiting toxicity during cycles 1-2. DISCUSSION: The maximum tolerated dose and
      recommended phase II dose of CPT-11 with hyperfractionated radiation therapy is
      10 mg/m(2)/d.

PMID- 15969990
TI  - Extraprostatic seed placement and its effect on seed loss.
AB  - PURPOSE: The purpose of this study was to examine the relationship between
      extraprostatic seed placement and seed loss in a cohort of patients who had
      underwent both computed tomographic (CT) and magnetic resonance (MR) scans at day
      0 and day 30 following brachytherapy. MATERIALS AND METHODS: Twenty-two patients
      with 1997 AJC clinical stage T1-T2 prostatic carcinoma were implanted with
      nonstranded I 125. Patients were selected solely by having a prostate volume
      between 15 and 60 cc and a willingness to return for 30-day follow-up CT and MR
      scans. The total number of I-125 sources implanted on day 0 ranged from 50 to 104
      (median: 70). Preplan treatment planning methods have been previously described
      in detail: a modified peripheral loading pattern and treatment margins of 5-10 mm
      were used. Noncontrast postimplantation CT and MR scans were obtained 1-4 hours
      after implantation on day 0. The total seed count on days 0 and 30 was verified
      by plain radiograph. Pelvic MR (T1) images were registered with the CT images in
      the Varian planning system, using bony landmarks. The number of extracapsular
      seeds in each quadrant of the circumference was then totaled for each patient. A
      second set of plain radiographs (for seed counting), as well as CT and MR scans,
      were obtained 30 days after implantation (day 30) and were similarly analyzed.
      RESULTS: The number of extraprostatic seeds at day 0 ranged from 13 to 35, making
      up 17%-48% (median: 34%) of the total number implanted. Of the 22 patients, 10
      lost one or more seeds between the implantation day and the 1-month follow-up.
      The mean number of seeds lost was 1.1 (+/- 1.7). There was no apparent
      relationship between the percent of extraprostatic seeds and the number of seeds
      lost. There was no apparent relationship between seed loss and number of seeds
      less than 3 mm or greater than 3 mm from the prostatic capsule. CONCLUSIONS: We
      have shown here that with CT and MR seed localization, extraprostatic seed
      placement does not appear to substantially increase the likelihood of seed loss
      after the procedure.

PMID- 15969991
TI  - Long-term results of ethmoid squamous cell or undifferentiated carcinoma treated
      with radiotherapy with or without surgery.
AB  - PURPOSE: Ethmoidal malignant tumors, for which intensity-modulated radiotherapy
      is expected to improve outcome, consist of heterogeneous pathological types.
      Reports about their outcome are influenced by the inclusion of favorable
      histology, such as adenocarcinoma and adenoid cystic carcinoma. We investigated
      the long-term treatment outcome of squamous cell carcinoma and undifferentiated
      carcinoma of the ethmoid sinus. MATERIALS AND METHODS: Between August 1976 and
      April 2002, 25 patients (20 squamous cell carcinomas and five undifferentiated
      carcinomas) received radical radiotherapy or preoperative radiotherapy in our
      institution. One (4%) had stage T2 disease, seven (28%) had stage T3, three (12%)
      had stage T4a, and 14 (56%) had stage T4b. Surgery was performed in 13 patients.
      Radiation dose varied from 50.4 Gy in 16 fractions (50.4 Gy/16 Fr) to 65 Gy in 26
      fractions with or without stereotactic boost irradiation. Eleven patients
      received chemotherapy consisting mainly of platinum-based compounds. RESULTS: The
      3- and 5-year overall survival rates for all 25 patients were 34% (95% confidence
      interval [CI]: 14%-54%) and 24% (CI: 6%-42%), respectively. The 3- or 5-year
      local progression-free rates for all patients were 48.9% and 36.7%, respectively.
      Visual acuity of a single eye was impaired in three patients and was lost in five
      patients as a result of tumor progression, but no patient had visual impairment
      or loss due to radiotherapy. CONCLUSION: Ethmoid squamous cell carcinoma or
      undifferentiated carcinoma was diagnosed at advanced T stages and was treated
      with radiotherapy; these patients had a poorer outcome than patients with
      adenocarcinoma or adenoid cystic carcinoma. Prospective trials using advanced
      technology should be carefully compared with historical controls because
      pathological types can considerably influence the treatment results.

PMID- 15969992
TI  - Port-A-Cath placement without the aid of fluoroscopy or localizing devices: a
      community hospital series.
AB  - BACKGROUND: Traditionally, Port-A-Caths are placed with the aid of intraoperative
      fluoroscopy or other localizing devices. Confirmation of catheter placement and
      location are made intraoperatively, and this practice adds considerable cost to
      the overall procedure with questionable benefit. We examined the experience of a
      community surgeon who does not use fluoroscopy or localizing devices to see
      whether this complication rate or need for manipulation of the catheter was high
      as well as cost savings per case. METHODS: A retrospective review of 107 Port-A
      Caths cases were evaluated for patient age, indication for port placement, sex,
      pneumothorax, need for repositioning of catheter, access site, catheter tip
      location, need for operative intervention related to port placement, and death.
      Location of the catheter was confirmed by dictated chest x-ray results and need
      for repositioning by the surgeon's operative note. Cost of fluoroscopy as well as
      C-arm use and chest x-ray studies were also used to calculate savings. RESULTS:
      Of the 107 Port-a-Cath cases, two (1.9%) pneumothoraces occurred and two (1.9%)
      catheters were repositioned; no deaths and no operative interventions related to
      Port-a-Cath placements occurred. Seventy-six (71%) of the ports were accessed via
      a left subclavian approach, and the remainder were accessed via right subclavian,
      right internal jugular, left internal jugular, and external jugular approaches.
      One catheter was repositioned due to a kink noted on postoperative chest x-ray
      study, and the other was noted to be ascending the left internal jugular vein.
      Cost of the C-arm was USD 174 for less than 1 hour and for fluoroscopy was USD
      396 for less than 1 hour. CONCLUSION: In our study, only two catheters (1.9%)
      needed to be repositioned. This comes at an estimated savings of USD 40,000 for
      this series. Based on our experience, Port-A-Caths can be placed safely without
      fluoroscopy or localization devices with no added morbidity and significant cost
      savings to the patient.

PMID- 15969994
TI  - Reproduction, genetics and the law.
AB  - Both reproductive medicine and genetics are seeing rapid, and in some instances
      revolutionary, medical and scientific advances. Courts have been called upon to
      resolve a variety of novel disputes arising from these areas, and more can be
      anticipated as these technologies continue to develop and their use becomes more
      widespread. This article discusses some of the most relevant areas of the law and
      litigation that currently bear on reproduction and genetics or that may be
      anticipated to do so in the future. Specific developments and judicial decisions
      addressing them include: legal theories of wrongful birth and wrongful life and
      their application to children born with genetic impairments; a physician's duty
      to warn family members about a relative's genetic disease; disputes over
      reproductive materials and non-reproductive cells and tissues; unauthorized
      genetic testing in the workplace; and genetic discrimination. It is hoped that
      this discussion will be of value to medical and legal professionals and policy
      makers who work with these concepts in the increasingly inter-related fields of
      law and medicine.

PMID- 15969995
TI  - China seeks good governance of research.

PMID- 15969996
TI  - GnRH antagonists in IVF.
AB  - The present review summarizes existing knowledge on the use of gonadotropin
      releasing hormone (GnRH) antagonists based on experience gathered after the
      completion of phase III comparative trials with GnRH agonists. Available data
      suggest that prolongation of the follicular phase significantly decreases the
      probability of pregnancy. Moreover, patients with elevated progesterone at
      initiation of stimulation have significantly fewer chances of achieving an
      ongoing pregnancy. Luteal support remains mandatory, while the replacement of
      human chorionic gonadotrophin by GnRH agonist does not appear to be feasible.
      Although not conclusive, existing data are not in favour of increasing the
      starting dose of gonadotrophins, of LH supplementation or of using a flexible
      antagonist protocol.

PMID- 15969997
TI  - Gurken activity in nurse cells polarizes Drosophila oocytes.

PMID- 15969998
TI  - Genetics of polycystic ovarian syndrome.
AB  - Polycystic ovarian syndrome (PCOS) is a reproductive system disorder
      characterized by irregular menses, anovulation, clinical and/or biochemical signs
      of hyperandrogenism (hirsutism and/or acne), ovarian micropolycystic appearance
      and metabolic abnormalities, such as hyperinsulinaemia and obesity. The
      aetiopathogenesis of this syndrome is not well known. Several pathogenetic
      hypotheses have been proposed to explain the full array of symptoms and signs,
      but with elusive results. A genetic abnormality causing PCOS is supported by the
      observation that different members of the same family are often affected, and
      about half of the sisters of PCOS women have elevated serum testosterone
      concentrations. Therefore, the presence of gene abnormalities in women with PCOS
      has been widely explored in the attempt to establish whether their mutations or
      polymorphisms may cause PCOS. The main genes evaluated are those involved in
      steroidogenesis, steroid hormone effects, gonadotrophin release regulation and
      action, insulin secretion and action, and adipose tissue metabolism. Despite the
      vast body of literature produced, none of the genes evaluated seems to play a key
      role in PCOS pathogenesis. It is likely that PCOS may represent the final outcome
      of different, deeply inter-related genetic abnormalities that influence each
      other and perpetuate the syndrome.

PMID- 15969999
TI  - Pancreatic stem cells grafted from mother to daughter.

PMID- 15970000
TI  - Hormonal manipulations in the luteal phase to coordinate subsequent antral
      follicle growth during ovarian stimulation.
AB  - During the early follicular phase in the menstrual cycle, antral follicle sizes
      are often markedly heterogeneous. These follicular size discrepancies may, at
      least in part, result from the early exposure of FSH-sensitive follicles to
      gradient FSH concentrations during the preceding luteal phase. In addition, they
      potentially affect the results of ovarian stimulation. Indeed, pre-existing
      follicle size discrepancies may encumber coordinated follicular growth during
      ovarian stimulation, thereby reducing the number of follicles that reach
      maturation at once. To investigate this issue, three clinical studies were
      conducted to test the hypothesis that luteal FSH suppression could coordinate
      follicular growth. First, luteal FSH concentrations were artificially lowered by
      administering physiological oestradiol doses and measured follicular
      characteristics on the subsequent day 3. Second, it was verified whether luteal
      oestradiol administration could promote the coordination of follicular growth
      during ovarian stimulation and improve its results. Third, the effects of
      premenstrual gonadotrophin-releasing hormone (GnRH) antagonist administration on
      follicular characteristics were assessed during the early follicular phase. The
      results showed that luteal FSH suppression by either oestradiol or GnRH
      antagonist administration reduces the size and improves the homogeneity of early
      antral follicles during the early follicular phase, an effect that persists
      during ovarian stimulation. Coordination of follicular development may optimize
      ovarian response to short GnRH agonist and antagonist protocols, and constitutes
      an attractive approach to improving their outcome.

PMID- 15970001
TI  - Methods for cryopreservation of human ovarian tissue.
AB  - Human ovarian tissue can be successfully cryopreserved, with good survival and
      function after thawing. Experimental animal studies regarding ovarian tissue
      cryopreservation resulting in live-born offspring preceded the present freezing
      systems in humans. On the basis of current knowledge, the standard method for
      human ovarian cryopreservation is slow programmed freezing, using human serum
      albumin-containing medium, and propanediol, dimethylsulphoxide (DMSO) or ethylene
      glycol as a cryoprotectant, combined with sucrose. Vitrification is still at the
      experimental stage. Whole organ cryopreservation is an interesting experimental
      option. Transplantation of the frozen-thawed tissue is a feasible method to
      utilize the tissue in infertility treatment. Ovarian function has been restored
      in humans. Because one healthy child has already been born from cryopreserved
      tissue, tissue cryopreservation should perhaps be offered to all young girls and
      women who can be predicted to undergo premature ovarian failure due to cancer
      treatment or genetic causes. Maturation of follicles in vitro from frozen-thawed
      tissue is another option that is still under development.

PMID- 15970002
TI  - Novel advances in IVF continue worldwide.

PMID- 15970003
TI  - Influence of spermatogenic profile and meiotic abnormalities on reproductive
      outcome of infertile patients.
AB  - Genetic aspects of male infertility and the possible risks of new assisted
      reproduction and their influence on the development of zygotes and children born
      after intracytoplasmic sperm injection (ICSI) need further research. These
      patients have an increased risk of diploidy, and disomies are frequent in their
      spermatozoa. Meiotic disorders are more common in testicular biopsies of patients
      with severe oligoasthenozoospermia. For these reasons, a detailed andrological
      study is absolutely mandatory before accepting a couple with these
      characteristics into an IVF-ICSI programme. When an andrological patient has
      plasma FSH values >10 IU/l and/or very low total motile sperm count <1 x 10(6),
      despite a normal karyotype, they clearly need a testicular biopsy and a meiotic
      study in order to rule out meiotic arrest or synaptic anomalies. Another
      important aspect to be considered is the possible benefit of applying
      preimplantation genetic diagnosis in these cases because they normally have a
      high percentage of chromosomally abnormal embryos, although in the present study
      this was not evident. All studies agree on the necessity of conducting follow-up
      studies in the population of children born after IVF-ICSI. In this way, it will
      be possible to find out if these infertile patients and their offspring have a
      higher risk of suffering epigenetic errors and imprinting disorders.

PMID- 15970004
TI  - Advantage of combining magnetic cell separation with sperm preparation
      techniques.
AB  - The selection of vital, non-apoptotic spermatozoa is a prerequisite for achieving
      optimal conception rates in assisted reproductive techniques. Magnetic cell
      sorting using annexin-V microbeads can effectively separate apoptotic and non
      apoptotic spermatozoa. The objective of the present study was to optimize the
      integration of magnetic cell sorting in standard sperm preparations and to
      correlate the effect of different sperm preparation procedures on apoptotic
      markers. Semen specimens collected from 15 healthy donors were prepared by either
      density gradient centrifugation or by one-step sperm wash technique separately
      and in combination with magnetic cell sorting. The preparation methods were
      evaluated by assessment of semen parameters (motility, viability and morphology)
      as well as markers of apoptosis (levels of active caspase-3, integrity of
      membrane mitochondrial potential and externalization of phosphatidylserine). The
      apoptotic markers were measured using fluorochrome dyes coupled with flow
      cytometry. The results showed that the combination of density gradient
      centrifugation and annexin-V magnetic cell sorting was superior to all other
      sperm preparation methods in terms of providing motile, viable and non-apoptotic
      spermatozoa. This study clearly shows the advantage of integrating magnetic cell
      sorting as a part of sperm preparation, which in turn may positively affect the
      success rates of assisted reproductive techniques.

PMID- 15970005
TI  - Novel mutations in testis-specific ubiquitin protease 26 gene may cause male
      infertility and hypogonadism.
AB  - Patients (n = 188) with non-obstructive azoospermia (NOA), and 17 fertile
      controls were screened for sequence changes in the ubiquitin specific protease
      (USP) 26 gene. Semen analysis, hormonal evaluation, and testicular biopsies were
      performed. DNA was extracted from whole blood. Denaturing high-performance liquid
      chromatography was used to screen for single nucleotide polymorphisms. Amino acid
      sequences were determined in samples with mutations. Twenty out of 188 (10.6%)
      infertile men had amino acid changes in USP26. No changes were found in fertile
      controls. 1090C-->T substitution and (363insACA; 494T-->C; 1423C-->T) change were
      found in 3.3 and 1.9% of patients respectively. Serum testosterone concentrations
      and testicular volume were lower in the mutation positive group compared with the
      non-mutation group (272 versus 366 ng/dl; P = 0.01) (volume: 7.88 versus 10 ml, P
      = 0.03). Six out of 28 (21%) patients with Sertoli cell-only syndrome, and two
      out of 18 (11%) patients with maturation arrest had mutations in the USP26 gene.
      There were no live deliveries in couples with the USP26+ mutation, and three live
      deliveries in the group without mutations. The USP26 gene may be of importance in
      male reproduction. Mutations in this gene may be associated with male
      infertility, and may negatively affect testicular function.

PMID- 15970006
TI  - Human embryonic stem cell methyl cycle enzyme expression: modelling epigenetic
      programming in assisted reproduction?
AB  - To investigate a possible mechanism for inducing epigenetic defects in the
      preimplantation embryo, a human embryonic stem cell model was developed, and gene
      expression of the key methyl cycle enzymes, MAT2A, MAT2B, GNMT, SAHH, CBS, CGL,
      MTR, MTRR, BHMT, BHMT2, mSHMT, cSHMT and MTHFR was demonstrated, while MAT1 was
      barely detectable. Several potential acceptors of cycle-generated methyl groups,
      the DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L), glycine
      methyltransferase and the polyamine biosynthetic enzymes, SAM decarboxylase and
      ornithine decarboxylase, were also expressed. Expression of folate receptor alpha
      suggests a propensity for folate metabolism. Methotrexate-induced depletion of
      folate resulted in elevated intracellular homocysteine concentration after 7 days
      in culture and a concomitant increase in cysteine and glutathione, indicating
      clearance of homocysteine through the transulphuration pathway. These studies
      indicate that altered methyl group metabolism provides a potential mechanism for
      inducing epigenetic changes in the preimplantation embryo.

PMID- 15970007
TI  - Does hysteroscopic polypectomy without cycle cancellation affect IVF?
AB  - Endometrial polyp (measuring <2 cm) was diagnosed by transvaginal ultrasonography
      performed on days 7 and 9 of the cycle in six patients who underwent IVF. These
      six patients were treated by hysteroscopic polypectomy preceding oocyte retrieval
      under general anaesthesia after informed consent was obtained. The cause of
      infertility was male factor in three patients, tubal factor in one, and two cases
      were unexplained. All patients had undergone ovulation induction and luteal
      support according to the long luteal protocol. As a result, in three cases
      pregnancy was achieved (one multiple and two singleton) and three cases were
      unsuccessful. One of the pregnant women gave birth at term, while the other two
      pregnancies are still ongoing. There is still no consensus regarding the
      management of patients diagnosed with endometrial polyp in IVF cycles.
      Cryopreservation, cycle cancellation and embryo transfer preceding polypectomy is
      the current management choice. The treatment modalities will be clarified only if
      embryo transfer preceding polypectomy in the same cycle is proven to be safe.
      This approach has been used in only six patients so far, and further studies with
      more patients are needed to confirm these findings.

PMID- 15970008
TI  - Pregnancy following intracytoplasmic sperm injection and preimplantation genetic
      diagnosis after the conservative management of endometrial cancer.
AB  - A rare case of a patient with conservatively treated endometrial carcinoma who
      conceived and delivered a healthy baby after the transfer of embryos with
      intracytoplasmic sperm injection (ICSI) and preimplantation genetic diagnosis
      (PGD) is presented. A 41-year-old woman had an office hysteroscopy in the
      infertility work-up and stage I endometrial adenocarcinoma was diagnosed. After
      conservative treatment, the patient underwent ICSI and PGD. She achieved
      pregnancy with two normal embryos. Two gestational sacs were observed but one of
      them was blighted. The patient subsequently delivered a healthy female infant.
      Repeated office hysteroscopy and endometrial sampling was performed after
      delivery. The appearance of the endometrium was normal on hysteroscopy, and the
      histology report was normal. The principal concern with medical therapy is that
      the lesion cannot be fully evaluated until the hysterectomy is performed, the
      nodes palpated, and the uterus is sectioned. The patient was referred to a
      gynaecological oncologist for definitive surgery.

PMID- 15970009
TI  - Role of clathrin in mitosis.

PMID- 15970010
TI  - Recombinant LH in ovarian stimulation.
AB  - The advent of recombinant gonadotrophins brought significant changes in fertility
      therapy. Treatment options with recombinant gonadotrophins add more to knowledge
      on folliculogenesis and ovarian steroidogenesis. Over a decade, recombinant LH
      (rLH) has been used for clinical trials, and the amount of peripheral LH that is
      necessary for optimal follicular growth, oocyte maturation, subsequent embryo
      development and assisted reproduction outcome during ovulation induction can now
      be better evaluated. This review evaluates the effect of rLH supplementation on
      ovarian stimulation and assisted reproduction outcome. The studies conducted with
      rLH supplementation in ovarian stimulation in different groups of patients and in
      cases of controlled ovarian stimulation are clearly discussed in this review.

PMID- 15970011
TI  - Significance of inhibin in reproductive pathophysiology and current clinical
      applications.
AB  - The human reproductive process is regulated by complex mechanisms that involve
      many organs, including the brain, gonads and endocrine system. It has been more
      than 70 years since the name 'inhibin' was used to describe a substance produced
      in the gonads that negatively regulates pituitary secretion. Inhibin B controls
      FSH secretion via a negative feedback mechanism. It is a glycoprotein hormone
      secreted by the Sertoli cells of the testis and granulosa and theca cells of the
      ovary. Serum inhibin B concentrations are positively related to testicular volume
      and sperm counts. Current understanding of inhibin physiology and pathology in
      the human suggests that inhibin B may be of importance as a marker of Sertoli
      cell function in men with infertility and as a prognostic indicator in women
      undergoing ovulation induction therapy. Inhibin concentrations are elevated in
      patients with granulosa cell tumours and in post-menopausal women with mucinous
      ovarian cancers. Immunoreactivity against the inhibin alpha-subunit was
      identified in all cases of adrenal cortical adenoma and carcinoma, and levels are
      suppressed in the malignant prostate disease. This article discusses the
      structure, regulation and clinical use of inhibin and other related substances.

PMID- 15970013
TI  - The Stockholm trial of HRT in breast cancer survivors.

PMID- 15970014
TI  - Muscle performance after the menopause.
AB  - The timing of the menopause transition has remained fairly constant throughout
      history. It represents a milestone in female health and, after passing through
      it, women experience increased musculoskeletal and cardiovascular morbidity.
      Muscle performance is an important determinant of functional capacity and quality
      of life among the elderly and is also involved in the maintenance of balance.
      Therefore, good muscle strength can prevent fragility fractures and lessen the
      burden of osteoporosis. Muscle strength begins to decline during the
      perimenopausal years and this phenomenon seems to be partly estrogen dependent.
      Randomized controlled trials have indicated that hormone replacement therapy may
      prevent a decline in muscle performance, although the exact mechanism of estrogen
      dependent sarcopenia remains to be clarified. Exercises have been shown to
      improve postmenopausal muscle performance and hormone replacement therapy may
      also potentiate these beneficial effects. Improvement or maintenance of muscle
      strength alone, however, may not be considered as a primary indication for long
      term hormone replacement therapy in view of current knowledge of its risks and
      benefits. Work history and educational background may be associated with
      postmenopausal muscle performance, which itself has unique associations with
      skeletal and cardiovascular diseases.

PMID- 15970015
TI  - Drug metabolism and ageing.
AB  - Older people are major consumers of drugs and because of this, as well as co
      morbidity and age-related changes in pharmacokinetics and pharmacodynamics, are
      at risk of associated adverse drug reactions. While age does not alter drug
      absorption in a clinically significant way, and age-related changes in volume of
      drug distribution and protein binding are not of concern in chronic therapy,
      reduction in hepatic drug clearance is clinically important. Liver blood flow
      falls by about 35% between young adulthood and old age, and liver size by about
      24-35% over the same period. First-pass metabolism of oral drugs avidly cleared
      by the liver and clearance of capacity-limited hepatically metabolized drugs fall
      in parallel with the fall in liver size, and clearance of drugs with a high
      hepatic extraction ratio falls in parallel with the fall in hepatic blood flow.
      In normal ageing, in general, activity of the cytochrome P450 enzymes is
      preserved, although a decline in frail older people has been noted, as well as in
      association with liver disease, cancer, trauma, sepsis, critical illness and
      renal failure. As the contribution of age, co-morbidity and concurrent drug
      therapy to altered drug clearance is impossible to predict in an individual older
      patient, it is wise to start any drug at a low dose and increase this slowly,
      monitoring carefully for beneficial and adverse effects.

PMID- 15970016
TI  - Home care for older people.
AB  - Older people receive home care either by choice or because alternative means of
      care are not available. The reasons for home care have an economic and cultural
      component; most of it is provided on a voluntary basis, regardless of the culture
      of the older person. Good home care, however, should not be left entirely to
      volunteers, but should be supported by the state through legislation and social
      policies, especially in the area of primary care and health promotion, as should
      end-of-life care. By these means some of the negative effects of home care on the
      recipient and the carer can be reduced.

PMID- 15970017
TI  - The menopause transition: endocrine changes and clinical symptoms.
AB  - Several biological changes take place during the menopause transition. The number
      of oocytes declines progressively from before birth but reaches a critically low
      level by the time of the menopause. The regular pattern of the menstrual cycle
      becomes disrupted and the frequency of normal ovulatory cycles declines. Rising
      gonadotrophin levels, particularly of follicle stimulating hormones (FSH), and
      declining estrogen levels are thought to characterize the menopausal transition.
      It now appears that declining levels of inhibin may play an important role in
      maintaining estrogen levels until just before the menopause, while causing
      increased levels of gonadotrophins. Wide variations in hormonal profiles between
      and within individuals occur. The clinical responses to this endocrine
      instability include vasomotor symptoms, psychological symptoms, sexual
      dysfunction and irregular menstrual bleeding. Estradiol deficiency induces a
      rapid phase of increased bone turnover in the early postmenopausal period, which
      can contribute to osteoporosis later in life. Similarly, changes in lipid
      profiles, particularly high-density lipoprotein (HDL) and triglycerides, can also
      occur.

PMID- 15970018
TI  - Advances in the understanding and treatment of ovarian cancer.
AB  - In England and Wales, ovarian cancer is responsible for more deaths than all
      other gynaecological cancers combined. Unlike cervical cancer, there is no
      effective population screening programme and the majority of women will present
      when the disease has spread beyond the ovaries. Current first-line management
      involves surgical debulking, followed by platinum-based chemotherapy. However,
      most women will relapse and the five-year survival rate is 20-30%. Novel
      therapies, based on an increasing understanding of the molecular biology of
      cancers, are being developed and evaluated in clinical trials.

PMID- 15970019
TI  - Homeopathy service in a National Health Service community menopause clinic: audit
      of clinical outcomes.
AB  - Sheffield's National Health Service community menopause clinic has run a
      homeopathy service since 1998. The service provides an alternative treatment
      option for those women who cannot take hormone replacement therapy, do not want
      it, have found it ineffective, or have been advised to stop it. Patients receive
      homeopathic treatment (monthly consultations plus individualized homeopathic
      medicines) for up to six sessions. An audit was undertaken of all patients
      referred to this service between 2001 and 2003, in which patients completed the
      Measure Yourself Medical Outcome Profile. Patients reported significant benefit
      from the service. The greatest response was seen in those reporting headaches,
      vasomotor symptoms, emotional/psychological symptoms and tiredness/fatigue as
      their primary symptoms.

PMID- 15970020
TI  - Hormone replacement therapy, thrombosis and thrombophilia.
AB  - Hormone replacement therapy increases the risk of venous thromboembolism. The
      risk is already increased in those with a personal or family history of
      thrombosis and in those with a hereditary thrombophilia. This article gives
      estimates of the absolute risk of using hormone replacement therapy and practical
      advice on its use in these groups and on the role of thrombophilia screening.

PMID- 15970021
TI  - Leprosy--a changing picture but a continuing challenge.

PMID- 15970022
TI  - Pyrexia of unknown origin: a review of studies from the developing world.

PMID- 15970023
TI  - The use of a monitoring tool to assess counselling and HIV testing in the public
      health sector in Malawi.
AB  - Scaling up of counselling and HIV testing (VCT) services requires a system of
      regular monitoring and evaluation. AVCT monitoring tool was developed through a
      consultative process and used to assess counselling and HIV testing services in
      16 government and mission hospitals in Malawi, which had started expanded HIV-TB
      activities in July 2003. The essential components of theVCT monitoring tool
      included assessments of: (i) the hospital VCT personnel, in particular the number
      of counsellors (full-time and part-time) and those trained in and performing
      whole blood rapid HIV testing; (ii) the hospital laboratory service, in
      particular the protocols for HIV testing; (iii) the number, structure and
      function of dedicated VCT rooms; (iv) registers for patients, clients and donors
      having HIV tests; and (v) the quality of VCT through structured interviews with
      HIV-positive patients with TB. The main findings were: 9644 patients and clients
      were HIV tested between July and September 2003; HIV testing protocols were not
      standardized and differed between hospitals; there was little in the way of
      external quality assurance and there were deficiencies in the counselling
      process. In each hospital, the mean time taken to obtain the data and complete
      theVCT monitoring tool was 3 h. TheVCT monitoring tool is straightforward to use,
      and the data collected should help to improve standardization, quality and future
      planning of VCT services in the country.

PMID- 15970024
TI  - Determinants of tetanus toxoid immunization in pregnancy in rural Bihar.
AB  - In order to increase the uptake of tetanus toxoid (TT) vaccination, we need to
      understand the factors that underlie the decision of the pregnant woman to
      undergo vaccination, especially in rural areas, where 75% of India's population
      resides. This paper constructs a model from a data-set of 2398 women in order to
      understand the determinants ofTTvaccine immunization by women during their most
      recent pregnancy and applies it to the National Family Health Survey-2 data. The
      object of the model is to predict the likelyhood of a pregnant woman receiving
      the recommended two doses of TT vaccine subject to other factors such as birth
      order, maternal education, prenatal care provider, household standard of living,
      health-care-seeking decision-maker and service availability. Policy implications
      of these findings are discussed.

PMID- 15970025
TI  - Clinical predictors of malaria and other febrile illnesses in children under five
      on Pemba Island, Tanzania.
AB  - Under the current guidelines of presumptive treatment of all children with
      reported fever, the risk of over-prescribing antimalarial drugs and missing other
      important causes of fever, like acute respiratory tract infection (ARI), is
      substantial. Clinical algorithms have been shown to be useful in diagnosing
      malaria, but often with differing results, due to regional variations. We set out
      to explore the clinical features associated with malaria compared with other
      febrile illnesses and specifically severe malaria with ARI in children under five
      in Pemba. Two hundred and seven children aged six months to five years presenting
      to a hospital clinic with fever were studied in Pemba. Clinical findings were
      related to the presence of malaria parasitaemia. Malaria accounted for 67.7% of
      the febrile episodes investigated. Five symptoms and signs, including pallor,
      drowsiness, splenomegaly, fever duration and no chest crackles, could accurately
      predict a case of malaria with a sensitivity of 91.3% and specificity of 53% and
      positive predictive value of 80.3%. Several clinical features were found to
      differentiate severe malaria from ARI. These results confirm that clinical
      algorithms can increase the diagnostic accuracy of malaria, although not
      sufficiently to replace microscopy, and by promoting the use of clinical skills
      other treatable causes of febrile illnesses may be identified. These findings
      could have implications in optimizing treatment and malaria control in children
      on Pemba.

PMID- 15970026
TI  - The mystery of the wooden leg: vitamin C deficiency in East African prisons.
AB  - Vitamin C deficiency (scurvy) is an uncommon disease in modern times, and
      therefore easily misdiagnosed when it appears. While visiting prisoners in East
      Africa, health delegates of the International Committee of the Red Cross (ICRC)
      encountered prisoners suffering from a hitherto undiagnosed 'mysterious' illness,
      consisting mainly of swollen and hard legs, that had not responded to various
      treatments given by the local health centre or hospital. The ICRC set out to
      investigate the nature of this disease and examined 133 prisoners with the
      suspected clinical symptoms described as 'wooden leg' syndrome in 10 different
      prisons. Serum ascorbic acid levels were measured and a food basket analysis
      done. The diagnosis of scurvy was confirmed. All patients responded to standard
      treatment with oral ascorbic acid. The clinical presentation of scurvy in these
      East African prisons seems to be somewhat different from the classic
      descriptions, but is in line with historic records of the disease. Treatment is
      easy and cheap, and response to treatment is quick. Scurvy remains a problem in
      prisons in Africa and clinicians working in prisons need to be aware of its
      presence and its presentations.

PMID- 15970027
TI  - Causes of acute peritonitis in 1188 consecutive adult patients in Ghana.
AB  - In a five-year prospective study, 1188 consecutive adult patients were admitted
      and treated for acute generalized peritonitis at the Surgical Emergency Unit of
      the Komfo Anokye Teaching Hospital, Kumasi, Ghana. Appendicitis and typhoid ileal
      perforation were the commonest causes, occurring in 43.1% and 35.1% of patients,
      respectively. Other conditions (gastroduodenal perforations, ruptured abscesses,
      traumatic bowel perforations and amoebic colonic perforations) accounted for
      fewer than 25% of cases.

PMID- 15970028
TI  - Adenosine deaminase activity in sera of patients with visceral leishmaniasis in
      Nepal.
AB  - This longitudinal study was conducted in BP Koirala Institute of Health Sciences
      (BPKIHS), a Medical University situated in eastern Nepal, between May 2001 and
      December 2001. The main objective of the study was to identify the role of
      adenosine deaminase (ADA) activity in patients with visceral leishmaniasis (VL)
      for management. There was a significant increase in mean ADA activity in sera of
      49 patients with VL (323.71+/-184.51 IU/L) compared with 50 samples of control
      groups (47.11+/-24.94 IU/L) from the same endemic area (P < 0.001). ADA
      activities were found to be significantly decreased (50.35+/-41.35 IU/L) in
      follow-up cases (n = 19) after 30 days with sodium stibogluconate treatment at a
      dose of 20 mg/kg/day intramuscularly. The fall in the level of ADAF (after
      treatment) in follow-up cases correlated with the cure of disease, as evident
      from improvement of vital signs and symptoms and the absence of Leishmania
      donavani bodies in the sera. The study therefore suggests the possibility of
      using human serum ADA as a convenient marker to evaluate the diagnosis of VL to
      support the clinical findings, especially in those settings where there is a lack
      of highly qualified personnel and diagnostic facilities.

PMID- 15970029
TI  - An indigenous spacer device for drug delivery in severely dyspnoeic patients.
AB  - Bronchodilator aerosols are commonly delivered through nebulizers or metered dose
      inhalers (MDI) to treat bronchospasm. Although the clinical results obtained with
      both these devices are comparable, the use of MDI offers several advantages like
      lower drug dose, reduced risk of complications, reliability of dosing, ease of
      administration, less personnel time and reduced cost. However, in non-intubated,
      spontaneously breathing patients, the amount of drug inhaled depends on the
      coordination of the inspiratory phase and delivery of the drug. In severely
      dyspnoeic or disoriented patients in the casualty department or intensive care
      settings, this is often not possible. Valved spacers and breath-actuated inhalers
      may not be easily available in such situations. Also, the spacer devices cannot
      be connected to the anatomical facemask and the need to discontinue oxygenation
      for aerosol delivery further limits their use.

PMID- 15970030
TI  - Overhead cubital angle as a measure of age.

PMID- 15970031
TI  - Pattern of malignant diseases at the University of Benin Teaching Hospital.
AB  - This study was designed to evaluate the pattern of malignant diseases seen at the
      University of Benin Teaching Hospital over a 20-year period (January 1980
      December 1999). A total of 2258 histologically confirmed malignant diseases were
      seen with the predominant tumours comprising carcinoma of the cervix (20.59%),
      breast (18.25%), prostate (7.13%), endometrium (6.47%) and colon and rectum
      (5.71%). We believe that the figure reported here represents an underestimate of
      the frequency of malignant tumours seen in the hospital and recommend the
      establishment of hospital- and population-based cancer registries to ensure
      proper documentation of malignant diseases within the region.

PMID- 15970032
TI  - Management and outcome of TB suspects admitted to the medical wards of a central
      hospital in Malawi.
AB  - In a study conducted in the medical wards of Lilongwe Central Hospital, Malawi,
      84 (18%) of 470 medical admissions were TB suspects. Of these, 21 (25%) had the
      diagnosis confirmed; the median length of time between admission and starting
      anti-TB treatment was 10 days. Of the remaining TB suspects, 24 (29%) had another
      diagnosis made, principally pneumonia, and 39 (46%) had no diagnosis made, with
      half of these patients dying under investigation in hospital. Improved and more
      rapid ways of managing TB suspects need to be found.

PMID- 15970033
TI  - Missed diagnosis of schistosomiasis leading to unnecessary surgical procedures in
      Jos University Teaching Hospital.
AB  - Twelve cases of radical surgery were carried out on patients with schistosoma
      granuloma mistaken for malignant lesions. Such radical procedures could have been
      averted if pre-operative biopsies were done. Therefore, there is a need for
      clinicians practising in schistosoma endemic areas to routinely carry out pre
      operative biopsy to minimize missed diagnosis of schistosomiasis.

PMID- 15970034
TI  - Filter paper strip kit: a cost-effective transport media.
AB  - This study was undertaken to discover a feasible transport media for the
      transportation of ocular microbiological material from the periphery to the
      central laboratory. A total of 94 cases of ocular infection with clinical
      diagnosis of conjunctivitis and keratitis were studied. In all cases, two
      representative microbiological samples were collected, and sent by filter paper
      strip (FPS) kit as well as by direct culture technique. The isolated organisms by
      both the methods were analysed. Of the total 94 cases studied, bacteria were
      isolated in 48 cases by direct culture and in 45 cases by FPS kit, whereas,
      fungus were isolated in 13 cases by each method. FPS kit appears to be an
      alternative, feasible, and cost-effective technique for transportation of ocular
      microbiological material from periphery to the central laboratory.

PMID- 15970035
TI  - Efficacy of garlic paste in oral candidiasis.
AB  - In a randomized trial of 56 patients, topical application of garlic paste for 14
      days was found to be as effective as that of clotrimazole solution in suppressing
      clinical signs of oral candidiasis. The results of this preliminary study explore
      the possible role of garlic paste in the treatment of oral candidiasis.

PMID- 15970036
TI  - Impact of mass media campaigns on the knowledge and attitudes of pregnant
      Nigerian women towards HIV/AIDS.
AB  - A total of 508 women coming for antinatal care had a structured interview about
      the risk factors for HIV/AIDS. While most knew about HIV and that it could be
      transmitted sexually, knowledge of mother-to-child transmission was poor. Only
      23% knew that HIV could be transmitted by breast milk. In all, 85% would not care
      for a relative with AIDS.

PMID- 15970037
TI  - Frequency of prenatal care visits by ethnic minority mothers and association with
      infant birthweight in Bac Kan Province, Vietnam.
AB  - The objective of this cross-sectional study was to evaluate the association
      between prenatal care visits and infant birthweight among ethnic minority mothers
      in the mountainous Bac Kan province. This was done by comparing the frequency and
      timing of first prenatal care visit of 32 mothers with low birthweight (LBW)
      infants and 32 mothers with normal birthweight (NBW) infants. During pregnancy,
      mothers of NBW infants underwent 3.4+/-1 (mean) prenatal care visits and mothers
      of LBW infants 2.8+/-0.9 (P = 0.02). Mothers of NBW infants underwent their first
      prenatal care visit at 13.1+/-5.7 weeks of gestation, one week earlier than
      mothers of LBW infants. The frequency of prenatal care visit are probably
      associated with a decreased risk of LBW among ethnic minority mothers in Bac Kan
      province.

PMID- 15970038
TI  - Incidence and pattern of cardiovascular disease in a Nigerian teaching hospital.
AB  - Epidemiological data on cardiovascular disorders are generally lacking in the
      developing nations. The aim of this study was to assess the five years' incidence
      and pattern of cardiovascular disease in a Nigerian Teaching Hospital. The
      records of patients diagnosed as having various cardiovascular disorders between
      1997 and 2001 were scrutinized. Data such as age, sex, diagnosis, length of
      hospitalization and status at discharge (dead or alive) were obtained. A total
      number of 1104 patients were recorded. Heart failure (35%) followed by
      hypertension (32%) was found to be the most prevalent.

PMID- 15970039
TI  - Long bone fractures treated by traditional bonesetters: a study of patients'
      behaviour.
AB  - This is a study of 295 patients (23.1% of 1278 patients with long bone fractures)
      who had visited the traditional bonesetter (TBS). The initial idea of visiting
      TBS was mooted by an external person in 75% of cases, whereas to discharge from
      TBS was usually the patient's idea. The reasons for a patient to opt for aTBS are
      explored.

PMID- 15970040
TI  - The value of the mini mental state examination in Nigerian epileptics.
AB  - This study assessed the role of the Mini Mental State examination (MMSE) in
      detecting cognitive impairment in Nigerian epileptics. The performance of 65
      epileptics on the MMSE was compared with that in 65 age- and education-matched
      controls. There were significantly more epileptics than controls with cognitive
      dysfunction and the epileptics also had significantly worse scores on the MMSE.
      The tests of attention, three-item recall and reading were the aspects of the
      MMSE that were most impaired in the epileptics.

PMID- 15970041
TI  - Determinants of utilization of antenatal care services in Kumbotso Village,
      northern Nigeria.
AB  - Women of childbearing age in a rural community in Kano state were interviewed to
      ascertain the determinants of utilization of antenatal care services in the
      village. Of the 200 women studied, 118 (59%) utilized antenatal care services
      during pregnancy. A majority (86%) of those who attained secondary school
      education, all of those with post-secondary education and 83% of those whose
      husbands had post-secondary education utilized antenatal care services.

PMID- 15970042
TI  - Prevalence of HIV infection in pregnant women in remote rural areas of Maharastra
      State, India.
AB  - In a study of 304 pregnant women, the prevalence of HIV infection in remote rural
      areas of western India was 0.7% (confidence interval 0.08-2.3%). It is nearly
      2(1/2) times higher than the presumed prevalence for this part of the country.

PMID- 15970043
TI  - First aid kit: a challenging new tool for traditional healers in Nepal.

PMID- 15970044
TI  - Causative agents of liver abscess in HIV-seropositive patients: a 10-year case
      series in Thai hospitalized patients.
AB  - Liver abscess is an important tropical gastrointestinal disorder. HIV
      seropositive patients show relative immunosuppression and are more susceptible to
      infection, including liver abscess. This retrospective case review was made on 23
      patients who were diagnosed as HIV seropositive with liver abscess in Bangkok,
      Thailand. We demonstrated the high rate of amoebic liver abscess in our series
      (17.4%) from fresh smear with five cases of tuberculosis and one case of
      Nocardosis. The rates of positive bacterial culture were 17.4% from blood and
      47.8% from pus. Gram-negative aerobes were the major abscess pathogens in our
      series. Among Gram-negative aerobes, Klebsiella was the most significant
      microorganism, followed by Escherichia coli and Pseudomonas aeruginosa.

PMID- 15970045
TI  - Photoallergy to quinine.

PMID- 15970046
TI  - Stevens-Johnson syndrome in two children in Ghana following anti-malarial
      treatment.

PMID- 15970047
TI  - Failure to complete the TB diagnostic algorithm in urban Peru: a study of
      contributing factors.

PMID- 15970048
TI  - Delta hepatitis in Pakistan.

PMID- 15970049
TI  - Acceptability and technical problems of the female condom in Malawi.

PMID- 15970050
TI  - Japanese encephalitis in India.

PMID- 15970051
TI  - Vesico-uterine fistula.

PMID- 15970052
TI  - Removal of a penetrating object.

PMID- 15970053
TI  - Factors leading to underreporting or under diagnosis of AIDS.

PMID- 15970054
TI  - Atraumatic sutures can be made locally.

PMID- 15970055
TI  - Oral hypotensives for severe hypertension.

PMID- 15970056
TI  - Concern over localized HIV/sexually transmitted infection epidemic during
      conflict in Nepal.

PMID- 15970057
TI  - HIV/AIDS pandemic and surgical practice in a Nigerian teaching hospital.

PMID- 15970058
TI  - Tetanus in Nigeria: the economic burden.

PMID- 15970059
TI  - Childhood skin infections and post-infective nephropathy.

PMID- 15970060
TI  - The tourniquet test is still a good screening tool for dengue illness.

PMID- 15970062
TI  - Haemoglobinopathy screening: an end to institutional racism?

PMID- 15970063
TI  - The changing face of assessment: swings and roundabouts.

PMID- 15970064
TI  - Making general practice fit for the 21st century.

PMID- 15970065
TI  - Antenatal screening for haemoglobinopathies in primary care: a whole system
      participatory action research project.
AB  - BACKGROUND: The usual system for antenatal screening for haemoglobinopathies
      permits termination only late in the second trimester of pregnancy. AIM: To
      evaluate a system where pregnant women are screened in general practice, and to
      develop a model of care pathway or whole system research able to bring into view
      unexpected effects of health service innovation. DESIGN OF STUDY: A whole system
      participatory action research approach was used. Six purposefully chosen general
      practices screened women who attended with a new pregnancy. Data of gestational
      age of screening were compared with two control groups. Qualitative data were
      gathered through workshops, interviews and feedback to the project steering
      group. At facilitated annual workshops participants from all parts of the care
      pathway produced a consensus about the meaning of the data as a whole. SETTING:
      Six general practices in north London. METHOD: A whole system participatory
      action research approach allowed stakeholders from throughout the care pathway to
      pilot the innovation and reflect on the meaning and significance of quantitative
      and qualitative data. RESULTS: The gestational age of screening in general
      practice was 4.1 weeks earlier (95% confidence interval (CI) = 3.41 to 4.68) than
      in hospital clinics (P<0.001), and 2.9 weeks earlier (95% CI = 2.07 to 3.65) than
      in community midwife clinics (P <0.001). However, only 35% of pregnant women in
      the study were screened in the practices. Changes required throughout the whole
      care pathway make wider implementation more difficult than at first realised. The
      cost within general practice is greater than initially appreciated owing to a
      perceived need to provide counselling about other issues at the same time.
      Practitioners considered that other ways of early screening should be explored,
      including preconceptual screening. The research approach was able to bring into
      view unexpected effects of the innovation, but health workers were unfamiliar
      with the participatory processes. CONCLUSION: Antenatal screening for
      haemoglobinopathies in general practice lowers the gestational age at which an at
      risk pregnancy can be identified. However, widespread implementation of such
      screening may be too difficult.

PMID- 15970066
TI  - What is being assessed in the MRCGP oral examination? A qualitative study.
AB  - BACKGROUND: Oral examinations are a popular method of assessment within medicine,
      being capable of measuring candidates' ability to carry out tasks or develop
      skills (operational knowledge). One example of this is the oral examination for
      membership of the Royal College of General Practitioners (RCGP), which is
      designed to assess candidates' decision-making skills and the professional values
      that underpin these decisions. While the reliability of oral examinations has
      been investigated, to date, little is known about their ability to measure what
      they set out to measure (validity). AIM: To investigate the content validity of
      the MRCGP oral examination, with particular focus on its ability to assess the
      process of decision-making. DESIGN OF STUDY: An evaluation of oral examination
      video recordings, using qualitative methods. METHOD: The MRCGP oral examinations
      are video recorded as part of an ongoing quality assurance programme. Fifty of
      the recordings carried out in 2002 were selected randomly and analysed for
      content and dialogue patterns reflecting the assessment of the decisionmaking
      process. RESULTS: All examiners used the specified contexts outlined in the
      examination objectives to present candidates with dilemmas. The assessment of
      decision-making skills, however, was limited by a tendency among examiners to
      present the candidate with new, more complex dilemmas rather than giving them the
      opportunity to discuss the implications, make choices and ultimately, justify
      their decision. Moreover, while examiners frequently asked candidates questions
      relating to professional values, they rarely asked them to demonstrate how those
      values support their decisions. CONCLUSION: In order that the benefits of oral
      examination can be fully realised, questions need to be structured in a way that
      encourages candidates to discuss all stages of the decision-making process.

PMID- 15970067
TI  - Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British
      South Asians with hypertension.
AB  - BACKGROUND: People from British South Asian communities have an increased risk of
      mortality from coronary heart disease (CHD). Doxazosin, a selective alpha(1)
      adrenergic blocker, in addition to lowering blood pressure, has been shown to
      have positive effects on glucose metabolism and lipid profiles in patients with
      hypertension. AIM: We studied doxazosin (1-8 mg) and bendrofluazide (2.5 mg) in
      patients of British South Asian origin with existing mild to moderate
      hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects
      on glucose and lipid metabolism in this group. DESIGN OF STUDY: A 34-week
      randomised, double-blind, parallel-group, multicentre study. SETTING: Primary
      care in the UK. METHOD: All doxazosin patients started with an initial dose of 1
      mg once daily, titrated to a maximum 8 mg once daily if diastolic blood pressure
      was >90 mmHg or was not <5 mmHg of the baseline value. The primary efficacy
      variables were mean glucose and total cholesterol concentrations at week 21.
      RESULT: Doxazosin reduced glucose, total cholesterol, low-density lipoprotein
      cholesterol and triglycerides and increased high-density lipoprotein-cholesterol.
      There were significant differences between doxazosin and bendrofluazide for
      glucose concentrations at week 21 (P = 0.029) and week 34 (P = 0.015), total
      cholesterol at week 21 (P = 0.048) and triglycerides at week 21 (P = 0.047) and
      week 34 (P = 0.009). There was no significant difference in blood pressure
      lowering between the two treatments. CONCLUSION: Doxazosin exhibits beneficial
      effects on glucose concentrations and lipid profile, in particular in lowering
      triglyceride concentrations in British South Asians. Whether these desirable
      characteristics translate to improved overall cardiovascular risk requires formal
      evaluation.

PMID- 15970069
TI  - GPs' assessment of patients' readiness to change diet, activity and smoking.
AB  - BACKGROUND: The Stages of Change Model is increasingly used for lifestyle
      counselling. In general practice, the use of algorithms to measure stage of
      change is limited, but for successful counselling it is important to know
      patients' readiness to change. AIM: To assess the accuracy of the assessment of
      patients' readiness to change fat consumption, physical activity, and smoking by
      GPs and general practice registrars. DESIGN OF STUDY: Cross-sectional
      questionnaire-based survey. SETTING: One hundred and ninety-nine patients at
      elevated cardiovascular risk aged 40-70 years, 24 GPs, and 21 registrars in Dutch
      general practices. METHOD: Patients were asked to complete an algorithm to
      measure their motivation to change fat consumption, physical activity, and
      smoking. GPs and registrars were given descriptions of the stages of change for
      the three lifestyles, and were asked to indicate the description that matched
      their patient. Cohen's kappa was calculated as measure of agreement between
      patients and GPs/registrars. RESULTS: Registrars' patients were younger, and less
      often overweight and hypertensive than GPs' patients. Cohen's kappa for smoking
      was moderate (0.50, 95% confidence interval [CI] = 0.34 to 0.67 for GPs and 0.47,
      CI = 0.27 to 0.68 for registrars). Agreement for fat and activity was poor to
      fair. No differences in accuracy were observed between GPs and registrars (P =
      0.07-0.83). CONCLUSIONS: Low accuracy indicates that counselling in general
      practice is often targeted at the wrong people at the wrong time. Improvements
      can possibly be achieved by making registration of lifestyle parameters in
      patient records common practice, and by simply asking patients where they stand
      in respect to lifestyle change.

PMID- 15970068
TI  - The prescribing of methadone and other opioids to addicts: national survey of GPs
      in England and Wales.
AB  - BACKGROUND: GPs occupy a pivotal position in relation to providing services to
      opiate misusers in the UK, and this is now cited to support initiatives in other
      countries. AIMS: To investigate GP involvement in the management of opiate
      misusers; and to examine the nature of this prescribing of methadone and other
      opioids. DESIGN: GP data collected via self-completion postal questionnaire from
      a 10% random sample of the 30 000 GPs across England and Wales. Patient
      prescription data obtained on opiate misusers treated during the preceding 4
      weeks. SETTING: Primary healthcare practice in England and Wales in mid-2001.
      METHOD: A questionnaire was mailed to a random 10% sample of GPs stratified by
      number of partners in the practice, with three follow-up mailshots. Data on drugs
      prescribed by these practitioners were also studied, including drug prescribed,
      form, dose and dispensing arrangements. RESULTS: The response rate was 66%.
      Opiate misusers had been seen by 51% of GPs in the preceding 4 weeks (mean of 4.1
      such patients), of whom 50% had prescribed opiate-substitution drugs. This
      provided a study sample of 1482 opiate misusers to whom GPs were prescribing
      methadone (86.7%), dihydrocodeine (8.5%) or buprenorphine (4.4%). Of 1292
      methadone prescriptions, mean daily dose was 36.9 mg - 47.9% being for 30 mg or
      less. Daily interval dispensing was stipulated by 44.6%, while 42.9% permitted
      weekly take-away supply. CONCLUSIONS: In 2001 nearly three times as many GPs were
      seeing opiate misusers than was the case in 1985. Half were prescribing
      substitute-opiate drugs such as methadone (to an estimated 30 000 patients).
      However, there are grounds for concern about the quality of this prescribing.
      Most doses were too low to constitute optimal methadone maintenance; widespread
      disregard of the availability of supervised or interval dispensing increases the
      risks of diversion to the blackmarket and deaths from methadone overdose.
      Increased quantity of care has been achieved. Increased quality is now required.

PMID- 15970070
TI  - Value of histopathologic analysis of skin excisions by GPs.
AB  - The clinical diagnoses of skin lesions in general practice may sometimes not be
      very accurate. The aim of this study was to compare clinical versus final
      histopathological diagnosis status (benign, pre-malignant/malignant) in 4595
      consecutive submissions by GPs. The final diagnosis was pre-malignant or
      malignant in 215 cases (4.7%). From the 4436 lesions clinically diagnosed as
      benign, 134 (3.0%) were pre-malignant or malignant on final histological
      diagnosis. From the 159 lesions clinically diagnosed as pre-malignant or
      malignant, 78 (49.1%) were in fact benign, and 81 (50.9%) were indeed pre
      malignant or malignant on final diagnosis. The sensitivity for a malignant
      diagnosis was 38%, and the specificity 98%. The proportion of pre-malignancies or
      malignancies was 0.9% below and 9.2% above the age of 40 years. In conclusion,
      histopathological investigation of skin excisions by GPs yields a high percentage
      of unexpected pre-malignancies and malignancies. The number of misdiagnoses was
      age dependent, with a proportion of 1% and 9% of pre-malignancies/malignancies in
      patients below and above the age of 40 years, respectively. This indicates that
      all skin excisions by GPs must undergo routine histopathological investigation to
      ensure that serious malignancies are not missed.

PMID- 15970071
TI  - Workplace assessment for licensing in general practice.
AB  - With the redesign of general practice training implicit in the Department of
      Health's programme of reform, Modernising Medical Careers, there is the
      opportunity to bring summative assessment and the MRCGP examination together into
      a unified assessment framework for licensing. It is likely that assessment in the
      workplace will play a central role in such a process. Workplace assessment is of
      high validity and has the potential to reconnect teaching and testing in general
      practice. Five principles to underpin the design of a workplace assessment are
      proposed, namely that it should be: competency-based, developmental, evidential,
      locally assessed, and triangulated. Successful implementation of workplace
      assessment will not only serve to reduce the current testing burden on trainees,
      but will also harness the involvement of medical teachers. In doing so, general
      practice has the opportunity to create a powerful tool for professional
      development.

PMID- 15970072
TI  - The clinical observer--on the up or over the hill?

PMID- 15970073
TI  - Unfair treatment.

PMID- 15970074
TI  - Interpreting differences over time in patient self-evaluation.

PMID- 15970076
TI  - Injecting drug users.

PMID- 15970078
TI  - Advance directives: awareness in care homes.

PMID- 15970083
TI  - Resistance and rebound.

PMID- 15970090
TI  - [Effects and appraisal of corticosteroid in the treatment of acute respiratory
      distress syndrome].

PMID- 15970091
TI  - [Scanning 2005 international consensus on guideline for cardiopulmonary
      resuscitation and emergency cardiovascular care (3): advanced life support: post
      resuscitation therapy].

PMID- 15970092
TI  - [Impact of disaster medicine as generalized from the characteristics and trend of
      development on medical support of United Nation peace maintaining activities in
      Liberia].

PMID- 15970093
TI  - [Changes in pulmonary function in severe acute respiratory syndrome patients
      during convalescent period].
AB  - OBJECTIVE: To investigate the changes and pattern of pulmonary function in severe
      acute respiratory syndrome (SARS) patients during convalescent period. METHODS:
      Pulmonary function tests were performed in 26 SARS convalescent patients
      regularly every 3 months after their discharge from hospital. The significance of
      changes in pulmonary function indexes was analyzed. RESULTS: Restrictive
      pulmonary ventilation function and diffusing dysfunction of the lung were found
      in one third of the patients during third to sixth month from onset. There was a
      little improvement in forced vital capacity (FVC), one second forced expiratory
      volume (FEV(1.0)), functional residual capacity (FRC) and residual volume (RV) as
      convalescent period was prolonged, but no difference was found between different
      stages (3-6 months, 6-9 months, 9-12 months, 12-15 months and 15-17 months).
      Meanwhile, the FEV(1.0)/FVC showed no significant change. However, there was an
      obvious improvement in total lung capacity (TLC) and diffusing capacity of the
      lung for carbon monoxide (DLCO) with the elapse of time, and also a significant
      difference was found between the later stage and the earlier stage. CONCLUSION:
      Pulmonary dysfunction is found among some SARS patients after convalescence
      presenting mainly as restrictive ventilatory function and diffusing capacity
      abnormality. These dysfunctions would improve gradually with the elapse of time.

PMID- 15970094
TI  - [Study of laboratory characteristic of 4 patients with sporadic severe acute
      respiratory syndrome in 2004].
AB  - OBJECTIVE: To analyze the laboratory characteristics of patients with sporadic
      severe acute respiratory syndrome (SARS) in China. METHODS: The laboratory
      findings of the 4 cases with SARS occurring in Guangzhou, People's Republic of
      China, in 2004 were analyzed and compared with that during epidemic. RESULTS:
      Leukopenia and lymphocytopenia were seen in all the patients. Two patients had
      slightly decreased peripheral blood T lymphocyte count. Alanine aminotransferase
      (ALT) and aspartate transaminase (AST) levels increased slightly in 3 patients.
      No hypoxemia was seen in all the patients. Both SARS-IgM and IgG sero-conversion
      occurred earlier in all the patients with the titer increased more than 4-fold
      shortly. Neutralization test was positive in all the patients. SARS coronary
      virus (SARS-CoV) RNA was detected by polymerase chain reaction (PCR) in
      pharyngeal swabs only in 1 patient. CONCLUSION: The 4 sporadic SARS patients in
      2004 have milder manifestations, shorter course of disease with no complications
      during an epidemic, compared with patients seen previously. The change in
      laboratory findings is less than that, which might be attributable to milder
      virulence of the SARS-CoV. The antibody appears earlier in these patients. The
      SARS-CoV is eliminated rapidly.

PMID- 15970096
TI  - [Prospective clinical study on serum immunity in IgG-antibodies positive patients
      convalescent from severe acute respiratory syndrome].
AB  - OBJECTIVE: To investigate the serum immunological characteristics in patients
      convalescent from severe acute respiratory syndrome (SARS). METHODS: In the 1 st,
      3 rd, 6 th month after their discharge, eg. SARS-IgG, T cell subsets, blood
      routine, and the blood biochemistry were systemically determined in SARS
      convalescent patients. RESULTS: The SARS-antibodies could be used as the
      diagnostic evidence. During the 6 months after discharge, the titers of SARS
      antibodies were high, but they lowered along with passage of time. At the first
      recheck, the CD4(+) lymphocyte count was lower than normal level in 55.9% of
      patients, the CD3(+) lymphocyte count was lower than normal level in 31.2% of
      patients, and the CD8(+) lymphocyte count was lower than normal level in 14.0% of
      patients. At the second recheck, the levels of T cell subsets recovered to normal
      level in the most patients. CONCLUSION: T cell subsets, and the number of
      leukocyte are abnormal in some patients convalescent from SARS. All the indexes
      examined recover to normal levels half year after discharge. Therefore, it is
      necessary to follow up the changes in the levels of SARS-antibodies.

PMID- 15970097
TI  - [Effects of interleukin-10 on expression of inflammatory mediators and anti
      inflammatory mediators during acute lung injury in rats].
AB  - OBJECTIVE: To investigate the effects of interleukin-10 (IL-10) on expression of
      inflammatory mediators and anti-inflammatory mediators during acute lung injury
      (ALI). METHODS: Rat model of ALI was reproduced by intratracheal instillation of
      lipopolysaccharide (LPS) in a dose of 10 mg/kg. Fifty-four male SD rats were
      randomly divided into control group, LPS group and LPS+IL-10 group, with 18 rats
      in each group (6 rats at 2, 6 and 24 hours respectively). Arterial gas analysis,
      the total protein concentration in bronchoalveolar lavage fluid (BALF), the total
      cell counts and classification in BALF, the lung coefficient, lung pathology were
      examined. Reverse transcription-polymerase chain reaction (RT-PCR) method was
      used to determine the expression of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and IL-1ra mRNA in lung tissue. RESULTS: (1)In LPS
      group the partial pressure of oxygen in artery (PaO(2)) was progressively
      decreased, while the lung coefficient, the total protein concentration, the total
      cell counts in BALF were greatly increased, and lung pathology showed severe
      polymorphonuclear leukocytes infiltration with bleeding and hyaline membranes
      formation. In LPS+IL-10 group the values of all above parameters were alleviated.
      (2)In LPS group TNF-alpha mRNA expression peaked at 2 hours, then decreased
      sharply; IL-1beta mRNA expression greatly increased at 2 hours, peaked at 6
      hours, then decreased; IL-1ra mRNA expression increased and peaked at 6 hours,
      remaining higher than control group at 24 hours. IL-10 inhibited TNF-alpha mRNA
      and IL-1beta mRNA expression but showed no effect on IL-1ra mRNA expression.
      CONCLUSION: (1)ALI is characterized by overwhelming expression of TNF-alpha mRNA,
      IL-1beta mRNA, while the expression of IL-1ra mRNA is much delayed than TNF-alpha
      mRNA and IL-1beta mRNA. It suggests that there is an imbalance between
      inflammatory/anti-inflammatory mediators in the early phase of ALI. (2)IL-10 can
      inhibit the expression of inflammatory mediators and has no effect on the
      expression of anti-inflammatory mediators, thus it contributes to the balance
      between them, ameliorating ALI in rats.

PMID- 15970098
TI  - [Study of serum uric acid changes after experimental pulmonary thromboembolism in
      rats].
AB  - OBJECTIVE: To study the change in serum uric acid (UA) after acute pulmonary
      thromboembolism (PTE) in rats and its value on the diagnosis of PTE. METHODS:
      Sixty-four male Sprague-Dawley rats were randomly divided into PTE group (n=34)
      and control group (n=30). Experimental PTE was induced in 34 rats by injection of
      auto-blood clots into the jugular vein (4 rats died and 30 survived), and another
      group of 30 rats underwent sham operation. Serum UA, partial pressure of oxygen
      in artery (PaO(2)), mean pulmonary arterial pressure (mPAP) and right ventricular
      pressure (RVP) were monitored on 1,4,7,14 and 28 days (n=6 per time point) after
      the operation. Lung tissue was harvested for histologic analysis using
      hematoxylin and eosin (HE) staining. RESULTS: Local hemorrhage in alveoli and
      inflammatory cell infiltration in interstitial tissue could be found
      microscopically within 1 week after PTE. The alveolar structure recovered and
      inflammatory cells in interstitial tissue decreased 7 days after PTE. Serum UA
      was higher in PTE group during 1-7 days after operation than in sham group (all
      P<0.05). PaO(2) was depressed markedly on 1,4 and 7 days after PTE (P<0.05 or
      P<0.01), and serum UA was negatively correlated with PaO(2) (r=-0.638, P<0.001);
      Serum UA returned to baseline 1 week after PTE, along with improvement of PaO(2)
      and alveolar hemorrhages. mPAP and RVP were not elevated in both groups.
      CONCLUSION: Serum UA content increases after experimental PTE in rats, and it may
      serve as a potential indicator of the severity and efficacy of treatment of PTE,
      but its clinical value need to be investigated.

PMID- 15970100
TI  - [Multiple organ dysfunction scoring system: comparison and evaluation of
      correlation and accuracy of the three scoring systems in predicting the outcome
      of multiple organ dysfunction syndrome on highland].
AB  - OBJECTIVE: To study the characteristics of the diagnostic parameters of acute
      respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H
      ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in
      predicting the outcome of syndrome. METHODS: Five hundred and forty cases
      fulfilling the criteria of MODS were divided into four groups according to the
      altitude of their inhabitation area: control group (on plain, CG, n=113,
      altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517
      m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and
      high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the
      diagnostic criteria of Lushan conference and Marshall (1995) commonly used on
      plain, and Lanzhou criteria drafted by the authors, three data analyzing models
      were set up to draw the receiver operating characteristic (ROC) curves, the
      Yordon Index and the optimum cutoff points of the parameters were calculated and
      the accuracy of the three respective diagnostic criteria was evaluated in
      predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of
      MODS were analyzed using the method of stepwise forward regress model. RESULTS:
      Following the increase in altitude, Lanzhou criteria was clearly superior to the
      other two criteria in the area of ROC, the sensitivity, the specificity, and also
      for the optimum cutoff points of MODS. Multi-variable regression analysis showed
      that the impacting factor of Lanzhou criteria was the highest (P<0.05).
      CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS
      are not suitable in moderately high or high altitude areas. It is necessary to
      set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics
      might change in areas 1,500 m altitude or higher. The pathophysiological
      mechanism might be attributable to peculiar biologic reactions due to hypoxia
      stress reaction, and it is worth further study.

PMID- 15970102
TI  - [Study of rat beta-defensin-2 gene and protein expression in ventilator
      associated pneumonia].
AB  - OBJECTIVE: To study the changes in the expression of rat beta-defensin-2 (RBD-2)
      gene in the lung tissue with P. aeruginosa (PA) pneumonia following tracheal
      mechanical ventilation (MV), and to evaluate the pathogenesis of ventilator
      associated pneumonia (VAP). METHODS: A total of 58 normal healthy Sprague-Dawley
      rats, weighing between 280 and 320 g, were randomly divided into the control
      group and the conventional MV group (CMV). A tracheal catheter was inserted via
      mouth in every rat under urethane anesthesia. PA (1 MIC, 0.2 ml) was instilled
      into the tracheal in the control group. Rats of CMV group received MV (V(T)=12
      ml/kg) through tracheal tube for 24 hours, and then were challenged intra
      tracheally with PA (1 MIC, 0.2 ml). Fluid loss was replenished through
      intravenous infusion. The arterial catheter was used for hemodynamics, parameters
      were monitored, and arterial blood gases were determined. Samples of lung were
      harvested at 0 hours, 15 hours, 3 hours, 6 hours, 12 hours, 1 day, 3 days and 5
      days, respectively, after bacterial challenge. The mRNA of RBD-2 was detected by
      reverse transcription-polymerase chain reaction (RT-PCR), and the protein levels
      were analyzed by Western blotting. RESULTS: Expression of RBD-2 mRNA and protein
      was lower in CMV group compared with the control 3 hours before instillation of
      bacteria. RBD-2 mRNA increased 3 hours after bacteria instillation, reaching the
      peak at 12-24 hours. No significant difference in RBD-2 expression between the
      control group and the CMV group within 3 hours, but it was significantly higher
      at 3 hours, 6 hours, 12 hours, 1 day, 3 days and 5 days in the control group than
      in the CMV group. The number of inflammatory cells infiltrating the bronchial
      submucous layer was significantly higher in the control group than in the CMV
      group (P<0.05). There was milder interstitial pulmonary edema and less red blood
      cells in the alveoli in the control group than in the CMV group. The mortality
      rate of the CMV group was 60%, which was significantly higher than that of the
      control group (20%, P<0.05). The positive rates of blood culture and
      bronchoalveolar lavage fluid (BALF) bacterial culture were also higher in the CMV
      group (P<0.05). The survival rate in CMV group (40%) was lower than that of the
      control group (P<0.05). CONCLUSION: The lowering of BD-2 gene and protein
      expression in the CMV group 3 hours after bacteria challenge might be one of the
      contributory factors in causing VAP.

PMID- 15970103
TI  - [Clinical study of the effect of verapamil-procaine compound in prevention and
      treatment of acute respiratory distress syndrome after high risk operation].
AB  - OBJECTIVE: To observe the effect of verapamil-procaine compound (V-P) on
      prevention and treatment of acute respiratory distress syndrome (ARDS) subsequent
      to high risk operation. METHODS: Altogether 150 cases of major operations with
      high risk of ARDS were enrolled for study. They were randomly divided into three
      groups. V-P group: 5% glucose 500 ml and procaine 1 250 mg and verapamil 10 mg;
      procaine group: 5% glucose 500 ml and procaine 1 250 mg; control group: only
      glucose was given. The injection speed of the three groups were the same, and it
      was kept at 0.5 ml x h(-1) x kg(-1). The dosages of verapamil and procaine in V-P
      group and procaine group were doubled when the diagnosis of acute lung injury
      (ALI) or ARDS was confirmed. UT4000F was used in monitoring (non-invasive) blood
      pressure (BP), electrocardiogram (ECG), pulse oxygen saturation (SpO(2)),
      respiratory rate, and temperature. Blood routine and arterial blood gases
      measurements were intermittently performed. Diagnosis of systemic inflammatory
      response syndrome (SIRS), ALI and ARDS was made respectively according to
      published diagnostic criteria. SIRS score and acute physiology and chronic health
      evaluation II (APACHEII) score were performed. RESULTS: Eleven cases in V-P
      group, 26 in procaine group, and 42 in control group manifested symptoms and
      signs of SIRS. There were notable differences among groups (all P<0.01). Four
      patients in V-P group, 7 in procaine group, and 19 in control group were shown to
      develop ALI. Significant difference was found between control and V-P or procaine
      group (both P<0.01), but no significant difference was found between procaine
      group and V-P group. Twelve cases were complicated with ARDS in control group 2
      weeks after the operation, and among them 5 died of multiple organ failure. There
      was significant difference between control group and V-P group or procaine group
      (both P<0.01). Two patients were complicated with acute renal failure in V-P
      group, 2 in procaine group, and 5 in control group. CONCLUSION: The V-P can
      interrupt SIRS to develop ALI, then ARDS and multiple organ dysfunction
      syndrome(MODS), and thus prevents and cures ARDS.

PMID- 15970104
TI  - [Study on the clinical significance of plasma adrenomedullin and brain
      natriuretic polypeptide in the patients with chronic cor pulmonale on highland].
AB  - OBJECTIVE: To study the clinical significance of plasma adrenomedullin (ADM) and
      brain natriuretic polypeptide (BNP) in the patients with chronic cor pulmonale on
      highland (HACCP). METHODS: The levels of ADM and BNP in plasma of 44 patients
      with HACCP in the acute and in the remission stages were determined with
      radioimmunoassay. Their correlations with partial pressure of oxygen in arterial
      blood (PaO(2)), endothelin-1 (ET-1), and the ratio of right ventricular pre
      ejection time to the pulmonary flow acceleration time (RVPEP/AT), which reflected
      the degree of pulmonary hypertension, were investigated. Twenty healthy subjects
      served as a normal control group. RESULTS: The levels of ADM [(38.8+/-7.2)ng/L
      and (26.2+/-5.3)ng/L] and BNP [(81.4+/-13.8)ng/L and (58.9+/-9.3)ng/L] in the
      acute and remission stages of cor pulmonale groups were both significantly higher
      than those in the normal control group [(15.0+/-3.2)ng/L, (38.6+/-3.4)ng/L,
      respectively, all P<0.01]. The levels of ADM and BNP in acute stage were both
      significantly higher than those in remission stage (both P<0.01). In the acute
      and in the remission stages, the levels of ADM in plasma were negatively
      correlated with PaO(2) (r(a)=-0.826, P<0.01; r(r)=-0.783, P<0.01), positively
      correlated with ET-1 (r(a)=0.755, P<0.01; r(r)=0.668, P<0.01) and RVPEP/AT ratio
      (r(a)=0.788, P<0.01; r(r)=0.734, P<0.01). In the acute and in the remission
      stages, the levels of BNP in plasma were negatively correlated with PaO(2) (r(a)=
      0.787, P<0.01; r(r)=-0.554, P<0.01), positively correlated with ET-1 (r(a)=0.725,
      P<0.01; r(r)=0.679, P<0.01) and RVPEP/AT ratio (r(a)=0.771, P<0.01; r(r)=0.722,
      P<0.01). CONCLUSION: The study suggests that ADM and BNP are involved in the
      pathophysiological process of HACCP in the patients and may play a compensatory
      role in the disease.

PMID- 15970105
TI  - [Prophylactic effect of ambroxol on acute hydrochloric acid aspiration - induced
      lung injury].
AB  - OBJECTIVE: To evaluate the protective effect of ambroxol, a muco-active drug, on
      acute hydrochloric acid-induced lung injury in rats. METHODS: Thirty pathogen
      free SD rats were randomly divided into three groups: group A (n=10) and group B
      (n=10) were injected normal saline (NS) intraperitoneally (6.7 ml/kg), and group
      C with ambroxol (50 mg/kg), once a day for 3 consecutive days. Then animals
      received in tracheal instillation of NS (group A, pH 5.3, 1.2 ml/kg) or
      hydrochloric acid/NS (group B and C, pH 1.25, 1.2 ml/kg). Five hours after
      instillation of the injury vehicle, the arterial gas was determined, and the
      extent of lung injury was assessed by measuring the ratio of wet to dry weight
      (W/D) and evaluation of pathological change in lung tissue. RESULTS: (1)Partial
      pressure of oxygen in arterial blood (PaO(2)) was significantly lower in group B
      than in groups A and C, although pH and partial pressure of carbon dioxide in
      arterial blood (PaCO(2)) in three groups showed little difference (all P<0.01).
      (2)The W/D was the highest in group B and the lowest in group A. (3)Severe acute
      lung injuries were detected in group B by pathological examination, the extent of
      injury was less in group C than in group B, but more severe than in group A
      (group A vs. B and B vs. C in mean pathologic score, P<0.01 and P<0.05,
      respectively). CONCLUSION: Hydrochloric-acid aspiration may induce an acute and
      diffuse lung injury, with manifestations of hyperpnea, lower PaO(2) and severe
      pathological changes in lung tissues. Ambroxol may have a protective effect
      against lung injury induced by hydrochloric acid.

PMID- 15970106
TI  - [Role of neutrophil activation in ventilator induced lung injury].
AB  - OBJECTIVE: To probe further the role of neutrophil activation in the lung injury
      induced by mechanical ventilation. METHODS: Thirty-two normal Wistar rats were
      randomly divided into four groups: control group, low tidal volume group,
      conventional tidal volume group, and high tidal volume group. The counts of white
      blood cell (WBC) and neutrophil in bronchoalveolar lavage fluid (BALF) were
      carried out. The levels of protein and myeloperoxidase (MPO) activity in plasma
      and BALF were determined by biochemical methods respectively. RESULTS: The
      numbers of WBC and neutrophils, and the levels of protein and MPO activity in
      BALF were significantly increased in normal and high tidal volume groups than
      those in control and low tidal volume groups (P<0.05 or P<0.01, respectively).
      The levels of protein and MPO activity in BALF in high tidal volume group were
      markedly higher compared with normal tidal volume group (both P<0.01), but no
      statistical differences existed between the low tidal volume group and the
      control group (both P>0.05). There were no significant differences in the levels
      of protein and MPO activity in plasma among the four groups (P>0.05). CONCLUSION:
      The recruitment and activation of neutrophils might play an important role in
      pathogenesis of the biotrauma induced by mechanical ventilation. MPO activity in
      BALF is a credible index in reflecting the activation of neutrophils. Measuring
      the level of protein in BALF is valuable to evaluate the extent of lung injury
      induced by mechanical ventilation.

PMID- 15970107
TI  - [Effects of combined naloxone and methylprednisolone on nuclear factor-kappaB
      expression in the lung in acute lung injury in rats].
AB  - OBJECTIVE: To investigate the effects of a combination of naloxone and
      methylprednisolone on nuclear factor-kappaB (NF-kappaB) p65 expression in the
      lung tissue in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats.
      METHODS: ALI models were reproduced by intratracheal instillation of LPS (3
      mg/kg). Four hours after LPS instillation, rats were randomly divided into five
      groups: normal saline group, LPS group, methylprednisolone group, naloxone group
      (LPS+naloxone) and combined drug group (LPS+naloxone+methylprednisolone). The
      level of interleukin-8 (IL-8) in serum was measured by immunoassay. Meanwhile,
      the expression of NF-kappaB p65 in the lung tissue was determined with
      immunohistochemical staining. RESULTS: Naloxone and methylprednisolone
      significantly reduced the LPS-induced increase in IL-8 concentrations in serum in
      vivo, and suppressed the activation of NF-kappaB p65 in the lung tissue.
      CONCLUSION: NF-kappaB activation is involved in the LPS-induced ALI in rats.
      Combination of naloxone and methylprednisolone could suppress the increase of IL
      8 content and NF-kappaB activation in the lung tissue of rat in vivo in our
      experiment.

PMID- 15970114
TI  - [One more reason to disseminate disease management programs for heart failure in
      Spain].

PMID- 15970115
TI  - [Inflammatory and anti-inflammatory markers in acute coronary syndromes. Ready
      for use in the clinical setting?].

PMID- 15970116
TI  - [Evaluation of a home-based intervention in heart failure patients. Results of a
      randomized study].
AB  - INTRODUCTION AND OBJECTIVES: Home-based interventions after hospital discharge in
      patients with heart failure (HF) have been shown to decrease readmission and
      mortality rates. The primary aim of this study was to determine the effect of a
      home-based educational intervention carried out by nursing staff on the
      readmission rate, emergency department visits, and healthcare costs. PATIENTS AND
      METHOD: Patients hospitalized with systolic HF were randomly assigned to receive
      either usual care or a single home-based educational intervention 1 week after
      discharge. RESULTS: Between July 2001 and November 2002, 70 patients entered the
      study: 34 in the intervention group and 36 in the control group. During the 6
      month follow-up, there were fewer unplanned readmissions in the intervention
      group than in the control group (0.09 vs 0.94; P<.001), fewer emergency
      department visits (0.21 vs 1.33; P<.001), and fewer out-of-hospital deaths (2 vs
      11; P<.01). Costs were also significantly lower in the intervention group
      (difference, ; 1190.9; P<.001). Moreover, patient-perceived health status, as
      indicated by scores on a quality-of-life questionnaire, increased significantly
      in the intervention group. CONCLUSIONS: In a cohort of patients with systolic HF
      who received a home-based educational intervention there were significant
      reductions in the unplanned readmission rate, mortality, and healthcare costs,
      and better quality of life. Some limitations of the study warrant validation of
      the resultats in further studies.

PMID- 15970117
TI  - [Association between serum interleukin 10 level and development of heart failure
      in acute myocardial infarction patients treated by primary angioplasty].
AB  - INTRODUCTION AND OBJECTIVES: Interleukin 10 (IL-10) is an anti-inflammatory
      cytokine that inhibits the synthesis of proinflammatory cytokines. It has been
      shown that IL-10 is released into the circulation during post-ischemic myocardial
      reperfusion. The objective of this study was to determine whether the serum IL-10
      concentration in patients with acute myocardial infarction who were undergoing
      primary angioplasty was related to the subsequent presence or absence of heart
      failure. PATIENTS AND METHOD: The study included 65 patients who underwent
      successful primary angioplasty. During their subsequent stay in the coronary
      unit, their maximum degree of heart failure was recorded. Patients were then
      divided into 2 groups: group A patients were in Killip class I and group B
      patients in Killip classes II-IV. The serum IL-10 concentration was measured
      during the 24 hours following admission to the coronary unit. RESULTS: The 2
      groups were similar with regard to age, sex, and coronary risk factors. The IL-10
      concentration was significantly higher in the group of patients with acute
      myocardial infarction without heart failure than in the group with heart failure
      (30.4+/-10.8 vs 19.8+/-7.9 pg/mL; P<.001). CONCLUSIONS: In patients with acute
      myocardial infarction who had undergone successful primary angioplasty, the serum
      IL-10 concentration measured during the following 24 hours was significantly
      higher in those who did not develop heart failure. These findings suggest that
      this anti-inflammatory cytokine has a protective effect on the myocardium during
      ischemia or reperfusion, or both.

PMID- 15970118
TI  - [Prognostic value of white blood cell count in acute myocardial infarction: long
      term mortality].
AB  - INTRODUCTION AND OBJECTIVES: Although traditionally an elevated white blood cell
      count (WBC), an indicator of systemic inflammation, has been accepted as part of
      the healing response following acute myocardial infarction (AMI), it has
      frequently been shown to be a predictor of adverse cardiovascular events. The
      present study was designed to assess the association between WBC and long-term
      mortality in AMI patients either with ST-segment elevation (STEMI) or without ST
      segment elevation (non-STEMI). Patients and method. The study included 1118
      consecutive patients who were admitted with the diagnosis of AMI: 569 non-STEMI
      and 549 STEMI. The WBC was measured in the 24 hours following admission. Patients
      were divided into 3 groups: WBC1 (count, <10 x 103 cells/mL), WBC2 (count, 10
      14.9 x 10(3) cells/mL), and WBC3 (count, > or =15x10(3) cells/mL). All-cause
      mortality was recorded during a median follow-up period of 10+/-2 months. The
      relationship between WBC and mortality was assessed by Cox regression analysis
      for both types of AMI. RESULTS: Long-term mortality during follow-up was 18.5% in
      non-STEMI patients and 19.9% in STEMI patients. In non-STEMI patients, the
      adjusted hazard ratios for those in the WBC3 and WBC2 groups compared with those
      in the WBC1 group were 2.07 (1.08-3.94; P=.027) and 1.61 (1.03-2.51; P=.036),
      respectively. The corresponding figures in STEMI patients were 2.07 (1.13-3.76;
      P=.017) and 2.22 (1.35-3.63; P=.002), respectively. CONCLUSIONS: WBC on admission
      was an independent predictor of long-term mortality in both non-STEMI and STEMI
      patients.

PMID- 15970119
TI  - [Effectiveness of a multifactorial strategy for implementing clinical guidelines
      on unstable angina: cluster randomized trial].
AB  - INTRODUCTION AND OBJECTIVES. Clinical practice in unstable angina is not always
      based on best evidence. Guidelines have the potential to improve quality of
      health care. There are no randomised trials assessing implementation strategies
      in the public healthcare system of Spain yet. OBJECTIVE: to compare the
      effectiveness of a multifaceted strategy (interactive educational meetings, local
      consensus process) for guideline implementation in unstable angina, with a
      passive dissemination strategy. Patients and method. SETTING: 10 wards from 3
      university hospitals in Sevilla. PARTICIPANTS: 153 specialists (cardiologists,
      internists) and their patients admitted for an unstable angina episode. DESIGN: a
      pragmatic, before and after cluster randomized controlled trial. Intervention was
      delivered from January to April 1998. Retrospective data collection took place in
      July 1999, of those pre and post-intervention episodes attended from January to
      October 1997 and from September 1998 to June 1999, respectively. OUTCOMES:
      compliance with the guideline recommendations for coronary angiography and stress
      testing, and ejection fraction assessment. RESULTS: The multifaceted strategy
      compared with the passive one, was associated with an absolute improvement in the
      appropriateness of use of coronary angiography and stress testing of 11% (95% CI,
      0.85-21.1), P=.03. There was no association for the assessment of the ejection
      fraction: absolute improvement of 1.1% (95% CI, --15.9 to 18.1), P=.88.
      CONCLUSIONS: Our results show that a combination of interactive educational
      meetings and local consensus process delivered to wards of physicians may improve
      the appropriateness of use of coronary angiography and stress testing.

PMID- 15970120
TI  - [Usefulness of parametric imaging-based quantitative myocardial contrast
      echocardiography in predicting the functional recovery of akinetic segments
      following primary angioplasty in acute myocardial infarction patients].
AB  - INTRODUCTION AND OBJECTIVES: Myocardial contrast echocardiography (MCE) is useful
      for predicting the functional recovery of akinetic segments in patients
      undergoing primary angioplasty after acute myocardial infraction (AMI). Recently,
      parametric imaging-based quantitative MCE has been developed for measuring
      perfusion. Our aims were: a) to measure perfusion in akinetic myocardial segments
      in patients undergoing primary angioplasty using parametric imaging-based
      quantitative MCE; and b) to assess the usefulness of these measurements in
      predicting functional recovery of these segments. PATIENTS AND METHOD: The study
      group comprised 49 consecutive patients undergoing primary angioplasty. Both MCE
      and standard echocardiography were performed between 2 and 5 days after AMI. Six
      months later, additional standard echocardiography and coronary angiography were
      performed. Perfusion was quantified independently off-line from parametric
      images. RESULTS: The patients' mean age was 62.3+/-14.5 years (39 men; 79.2%).
      Some 170 akinetic segments were detected. Of these, 105 (62.1%) recovered
      function. The quantitative MCE parameter that best predicted functional recovery
      was myocardial blood flow velocity (beta): the area under the receiver operating
      characteristic (ROC) curve was 0.96 (95% CI, 0.92-0.99). For a cut-off point of
      31 dB/s, the sensitivity was 87.62%, the specificity was 95.31%, the positive
      predictive value was 96.8%, and the negative predictive value was 82.43%. These
      results were better than those obtained using qualitative methods for assessing
      myocardial perfusion. CONCLUSIONS: Perfusion measurement by parametric imaging
      based quantitative MCE is useful for predicting the functional recovery of
      akinetic segments in patients undergoing primary angioplasty after AMI. The
      technique provides superior information to older qualitative methods.

PMID- 15970121
TI  - [Analysis of the frequency of cardiac arrhythmias and conduction disturbances
      from a health-care perspective].
AB  - INTRODUCTION AND OBJECTIVES: Over the last few years, our understanding of the
      mechanisms underlying cardiac arrhythmias has increased substantially. However,
      few data on their prevalence exist. Our objectives were to analyze the prevalence
      of cardiac arrhythmias and conduction disturbances in cardiology clinic
      outpatients and to determine the number of patients with a class-I or -IIa
      recommendation for electrophysiological studies (EPS). PATIENTS AND METHOD: We
      investigated cardiac arrhythmias and conduction disturbances in 2045 patients and
      determined their prevalence in those seen for the first time. Specific conditions
      investigated included supraventricular and ventricular arrhythmias, ischemic
      disease with an ejection fraction (EF) <30%, second-degree or higher
      atrioventricular (AV) block, intraventricular block, and sick sinus syndrome.
      RESULTS: In total, 798 (39%) of all patients and 153 of the 704 (22%) seen for
      the first time presented with 1 or more of the specified conditions. Their
      distribution in all patients was: atrial fibrillation, 524 (26%); atrial flutter,
      34 (2%); narrow-QRS tachycardia, 58 (3%); ventricular arrhythmias or EF<30% due
      to ischemic disease or both, 46 (2%); AV block or sinus dysfunction, 68 (3%);
      intraventricular block, 157 (8%); and other conditions, 4 (0.2%). Some 7%
      (143/2045) of all patients and 3.5% (25/704) of those seen for the first time had
      an indication for EPS. CONCLUSIONS: a) Almost 40% of all patients seen in a
      cardiology outpatient clinic and 1 in 4 of those seen for the first time
      presented with a cardiac arrhythmia or conduction disturbance; and b) more than
      3% of patients seen for the first time had an indication for EPS.

PMID- 15970123
TI  - [Guidelines for percutaneous coronary interventions].

PMID- 15970124
TI  - [Advances in adjunctive pharmacological therapy for percutaneous coronary
      interventions].
AB  - All percutaneous interventions disrupt atherosclerotic plaque and denude the
      endothelium. These processes stimulate both platelet aggregation and the
      coagulation cascade. Therefore, pharmacological treatment during percutaneous
      intervention is based on the use of antithrombotic agents. In addition to
      aspirin, whose benefit has been clearly demonstrated in all forms of ischemic
      heart disease, clopidogrel, given before and after cardiac catheterization, also
      reduces the rate of thrombosis after stent placement. Moreover, the introduction
      of glycoprotein IIb/IIIa inhibitors has improved the results of percutaneous
      revascularization, especially in high-risk patients. On the other hand,
      anticoagulants are essential for preventing the acute thrombotic complications
      that result from the invasive nature of the procedure. Low-molecular-weight
      heparins, direct thrombin inhibitors (e.g., hirudin and its derivatives), and
      recently developed pentasaccharides, which inhibit factor X, provide new
      alternatives to classical unfractionated heparin. These novel compounds lead to
      fewer hemorrhagic complications than unfractionated heparin and do not require
      such extensive monitoring. Finally, new antiproliferative agents, such as oral
      rapamycin, have been introduced to reduce the rate of coronary restenosis during
      follow-up.

PMID- 15970125
TI  - [Aortic intramural hematoma: discovered during coronary bypass surgery].

PMID- 15970126
TI  - [Pharmacogenetic study of the response to flecainide and propafenone in patients
      with atrial fibrillation].
AB  - We analyzed cytochrome P450 2D6 polymorphism by determining phenotype as the
      metabolic ratio between dextromethorphan and its main metabolite, dextrorphan. We
      studied 18 men and 22 women in whom mean age was 54.6+/-11.9 years. In 9 patients
      metabolic ratio was determined before antiarrhythmic treatment and again during
      treatment, with a mean increase of 0.13+/-0.15 (P=.03). We found 19 poor
      metabolizers and 21 extensive metabolizers. Adverse effects were more frequent in
      poor metabolizers (21.1%) than in extensive metabolizers (4.8%; P=.12).
      Antiarrhythmic treatment was effective in 27 patients (67.5%), with no difference
      between poor and extensive metabolizers.

PMID- 15970127
TI  - [Current profile of left-sided native valve endocarditis caused by coagulase
      negative Staphylococcus].
AB  - Coagulase-negative staphylococci are the most frequently isolated microorganisms
      in early prosthetic valve endocarditis. However, they rarely cause endocarditis
      in native valves. The profile of patients with left-sided native valve
      endocarditis by coagulase-negative staphylococci is unknown, because available
      data are scarce and outdated. We analyzed the epidemiological, clinical,
      radiographic, microbiological, and echocardiographic features and clinical course
      in 17 patients with this entity out of a total of 441 consecutive patients
      diagnosed as having endocarditis. The results show that left-sided native valve
      endocarditis caused by coagulase-negative staphylococci is more common than
      previously reported, can cause heart failure due to valvular involvement, often
      needs surgery, and is associated with high mortality.

PMID- 15970128
TI  - [Diagnosis of acute myocarditis by contrast-enhanced cardiac magnetic resonance
      imaging].
AB  - Myocarditis is defined as an inflammatory process of the heart muscle. The
      symptoms are often nonspecific, and it can mimic acute coronary syndrome.
      Although the majority of patients recover fully, in some cases myocarditis can
      lead to dilated cardiomyopathy and even death. Available diagnostic tools are
      unsatisfactory and there is a need to develop noninvasive techniques that can aid
      diagnosis, prognosis, and follow-up. Contrast-enhanced magnetic resonance imaging
      is a valuable tool for the evaluation of inflammatory heart diseases such as
      myocarditis. We describe a 39-year-old man presenting in the emergency department
      with chest pain, ST segment elevation and elevated cardiac enzymes, who was
      treated initially with thrombolysis. Coronary angiography showed normal coronary
      arteries. Magnetic resonance imaging showed focally delayed uptake of gadolinium
      with a patchy pattern typical of myocarditis.

PMID- 15970129
TI  - [Optimized transseptal approach for left ventricular tachycardia ablation in a
      patient with a mechanical prosthetic aortic valve].
AB  - Prosthetic valves may make ventricular access difficult in radiofrequency
      catheter ablation. This case report describes an optimized atrial transseptal
      approach to access the ventricle in a patient with left ventricular tachycardia
      and a mechanical prosthetic aortic valve.

PMID- 15970131
TI  - [Internet prescriptions].

PMID- 15970132
TI  - [Internet application for medical purposes in chronic patients cared in a
      systemic autoimmune diseases unit].
AB  - OBJECTIVE: In recent years Internet has become an important tool for medical
      information search, not only for physicians but also for the patients. Little is
      known about Internet patient's use in Spain. Our objective was to study the
      frequency with which patients with different chronic autoimmune diseases cared in
      our unit use Internet as a source of medical information, and to identify the
      factors associated with its use. METHODS: A survey was carried out on Internet
      use to patients cared in a teaching hospital Systemic Autoimmune Diseases unit
      along three consecutive weeks. RESULTS: Hundred thirty-eight patients completed
      the questionnaire. Eighty-seven (63%) were women. Fifty-four patients (39.1%)
      were older than 55 years. Mean disease progression was 34.2 +/- 39.2 months. 22%
      of the respondents were uneducated, 39% had elementary education level; 20% had
      average education level, and 20% had advanced education level. Forty-two patients
      (30.4%) used regularly Internet for any purpose. Factors associated to Internet
      use for medical purposes were regular Internet use (OR: 4.6; CI: 1.1-18.8;p =
      0.03), and average or advanced educational degree (advanced education: OR: 22.9;
      CI: 2.6-202.7; p = 0.005; average education: OR: 8.5; CI: 1.2-59.6; p = 0.03).
      Eighty-one patients (58.7%) expressed their need of information on quality web
      pages. CONCLUSIONS: Many patients use Internet for medical purposes in our
      environment and even more consider to use it in the future. It is important to be
      aware of this fact and facilitate information about quality web pages for
      interested patients.

PMID- 15970133
TI  - [Antibiotic resistance transformation in community-acquired urinary infections].
AB  - OBJECTIVE: To detect the prevalence of uropathogens in community-acquired urinary
      tract infection in our environment, and the degree of sensitivity to antibiotics
      used as empirical treatment. PATIENTS AND METHOD: Retrospective longitudinal
      study on 16,392 consecutive urine cultures collected in the emergency department
      of Hospital del Mar, between January 1997 and December 2001. Resistance rates
      were compared through variance analysis. RESULTS: 8,743 urine cultures with
      significant count were obtained. 6,062 Escherichia coli (69.3%), 517 Proteus
      mirabilis (5.9%) and 390 Klebsiella pneumoniae (4.5%) were identified.
      Escherichia coli showed progressive growth rate and significant resistances to
      most of antibiotics evaluated, especially to quinolones which came close to 30%.
      Fosfomycin showed the least resistance rate (0.9%) and remained stable along the
      years studied. CONCLUSIONS: These results suggest that higher rate of resistance
      to quinolones does not advise its use as empirical in community-acquired urinary
      tract infection treatment in our environment. According to our experience,
      fosfomycin can be an excellent option for cystitis treatment in patients without
      risk factors, while for the treatment of parenchymatous urinary tract infection,
      complicated urinary tract infections, and urinary tract infections associated to
      risk factors, preference could be second or third generation oral cephalosporins,
      or amoxicillin-clavulanic acid.

PMID- 15970134
TI  - [Hierarchical structure of authors collaboration. An analysis of papers on
      imaging diagnosis published by hospital radiology departments in Comunidad
      Valenciana (1994-2001)].
AB  - OBJECTIVE: Analyze the different contribution of hierarchical categories in the
      papers published by radiologists of hospitals belonging to Comunidad Valenciana
      along the period 1994-2001, as well as their distribution in the different
      journals. MATERIAL AND METHODS: For the recovery of the papers sample we have
      designed specific search profiles for EMI and Medline databases. Hierarchical
      category of the authors was identified through personal interviews. RESULTS: We
      have analyzed 417 works, with 1,321 authors distributed in the following form:
      chief of service, 8.8%; chief of section, 12.4%; assistant physician, 50.7%, and
      resident, 28%. Hierarchical groupings with participation of residents were more
      consistent for publishing papers along all the study period (1994-2001). Higher
      percentage of papers (21%) corresponded to <<residents + adjunct physicians>>
      grouping. Radiologia was the most productive journal (42% papers). All results
      were statistically significant (p < 0.0001). CONCLUSION: Radiodiagnosis residents
      of Comunidad Valenciana hospitals showed an active participation in research
      papers published along the period 1994-2001, in collaboration with the rest of
      the hierarchical categories, basically with the assistant physician. Assistant
      physicians contributed most of papers. Chief of section and chief of department
      contributed fifth of papers.

PMID- 15970135
TI  - [Degree of satisfaction of primary health workers regarding a consultancy-based
      specialty care model].
AB  - OBJECTIVE: To evaluate the degree of satisfaction of primary health care workers
      with a model of specialty care based on consultancy. METHODS: A questionnaire was
      delivered to the nurses and physicians of a Primary Care centre, in order to
      assess their satisfaction with the different activities in the specialty of
      endocrinology (1-5 points). RESULTS: The consultancy activity itself was given
      4.41 +/- 0.89 points by the nurses (n = 39) and 3.60 +/- 0.97 by physicians (n =
      32) (p < 0.05), clinical sessions, 4.21 +/- 0.74 and 3.82 +/- 1.02, and
      diagnostic and therapeutic protocols, 4.12 +/- 0.71 points (physicians) (p < 0.05
      vs consultancy). Global scores was 4.33 +/- 0.70 and 3.76 +/- 0.89 points,
      respectively. 74% and 80% of the nurses and 58% and 69% of the physicians
      considered the present model appropriate for other specialties and primary care
      center, respectively. CONCLUSIONS: The health care workers at the primary care
      center assesse show a high degree of satisfaction with this model of specialised
      care based on consultancy.

PMID- 15970136
TI  - [Central nervous system infections in HIV patients in the era of high activity
      antiretroviral treatment].
AB  - Although the incidence of most central nervous system infections in HIV+ patients
      has decreased after the introduction of the modern antiretroviral treatments,
      they are still a major cause of morbidity and mortality. New technologies in
      molecular biology and neuroradiology establish the diagnosis in many cases and
      have decreased the need for cerebral biopsy. Prognosis has improved substantially
      after the introduction of high activity antiretroviral treatment; more active
      treatments are needed, however, for infections as PML or citomegalovirus
      encephalitis because of their still unacceptably high mortality.

PMID- 15970137
TI  - [Chronobiology, chronotherapy and vascular risk].
AB  - The importance of rhythmic activities in humans, and their influence on the
      diseases are underscored. Clinical chronology is fundamental in order to
      interpret the physiopathological basis of temporary variations. Knowing the
      variability of the biological processes also makes it possible improving the
      effect of drugs utilized and minimize their adverse effects. This is the
      objective of Chronotherapy. We apply chronology and Chronotherapy in
      cardiovascular diseases, since many of them adjust their prevalence for specific
      rhythms. One thinks about the mechanisms or factors that favor cardiovascular
      diseases, especially those related to the circadian variations of blood pressure.
      We also review the variations in the pharmacokinetics of the drugs used in the
      treatment of cardiovascular diseases, delving further into the analysis of its
      effects according to their administration schedule. We can conclude that the use
      of those drugs according to the chronological knowledge makes possible to achieve
      better results in the control of cardiovascular diseases, and a greater safety in
      its use.

PMID- 15970138
TI  - [Medical communication with immigrant population lacking language fluidity].
AB  - The Guadalajara University Hospital Study on the quality of communication with
      immigrant population is a pilot experience that once finished and its success
      assessed could be extended to other health centers and to others JCCM provinces,
      and could even coordinate the translation of materials at regional level. Without
      a doubt the health center would decrease the risk of errors in communication,
      saving time and consequently money if professionals for increase the process of
      communication were hired, with quality assurances and materials for the users
      translated into the most requiered languages, and cultural informative materials
      for health professionals, all of them areas we are already working on. For the
      formation of skilled personal, we are working in a pocket guide in several
      languages; for the user we have an admission guide in Arab and English, protocols
      and informed consents, as well as informative pamphlets in several languages. The
      situation has been and is similar in other European countries but measures have
      been taken or are being taken for paying more attention to linguistic problems.
      According to our data in Spain no support service for health professionals or for
      patients is available in this regard, being implied that those involved should
      resolve the communicative conflicts with effort and time.

PMID- 15970139
TI  - [Glycemic control and new prospects on insulinotherapy in diabetes mellitus type
      1].
AB  - Except for contraindications, current treatment of DM1 is based on what we know
      as insulin intensive treatment. This modality includes the utilization of rapid
      insulins for controlling the postprandial hyperglycemic peaks, and insulins of
      intermediate or slow action with the objective of contributing some basal levels
      of insulin (bolus/basal type therapy). Although the intensive treatment does not
      avoid completely the appearance nor the progression of the microvascular
      complications, improvement of glycemic control reduces the risk of developing
      microvascular complications approximately between 35% and 75%, and its worsening
      diminishes the risk between 50% and 75%. New insulin analogues has possibly many
      and obvious advantages. New insulin analogues are a potentially effective
      alternative in the intensive treatment of the patients with DM1, and they
      represent the best way for implementing a <<bolus-basal>> type therapeutic
      regimen. Its balanced and individualized application can contribute for
      improvement metabolic control, including a reduction in the incidence of
      hypoglycemia.

PMID- 15970140
TI  - [Exposition. Case 1. Hyperpigmented and photosensitive lesions associated to
      carcinoid syndrome].

PMID- 15970141
TI  - [Case 2. Lung mass and contralateral pleural effusion].

PMID- 15970142
TI  - [Case 3. Chest pain and dyspnea in a 39-year-old woman].

PMID- 15970145
TI  - [Influenza vaccination and pneumococcal vaccination in patients cared in an
      internal medicine department].

PMID- 15970148
TI  - [Antiretroviral treatment compliance].

PMID- 15970146
TI  - [Kikuchi disease and tuberculosis].

PMID- 15970149
TI  - [Geriatric physical performance assessment in an emergency department].
AB  - BASIS: Premorbid situation with regard to daily life activities is an important
      prognostic factor in elderly people who needs medical care. This work analyzes
      the way the parameter evaluation of core processes of daily life (CPDL) is made
      in patients over 70 years cared in an Emergency Service because of diverse
      medical conditions. PATIENTS AND METHODS: A prospective study, carried out in a
      third level medical institution, on 200 patients over 70 years cared in the
      Emergency medical Service, with questioning a group of 60 physicians on duty
      (POD) about the informal or subjective assessments of five parameters of CPDL (to
      get dressed, to be fed, sphincter control, walking, and transfer). POD evaluation
      is compared with evaluation carried out formally by the research physician.
      Assessments are evaluated, grouping the patients according to the degree of
      dependency, age, or sex. RESULTS: 82% of most dependent patients and 53% of those
      older than 80 years were poorly assessed, and both parameters were statistically
      significant. The analysis with multiple linear regression showed that the
      intensity of these errors is only determined by a variable: the greater degree of
      dependency. CONCLUSIONS: Correct performance assessment of elderly patients in
      emergency services, especially of those older and most dependent, requires a
      specific training of professionals in this regard and the use of formal
      instruments of evaluation.

PMID- 15970150
TI  - [Monoclonal gammopathy: a frequently overlooked diagnosis].
AB  - OBJECTIVE: To know the rate of occurrence of monoclonal bands in a clinical
      laboratory as an estimate of monoclonal gammopathy incidence, and to detect the
      proportion of these bands in which an explicit clinical diagnosis or follow-up
      request is not established. Other objectives are to describe its distribution and
      the characteristics of the patients. PATIENTS AND METHODS: 200 patients were
      studied in which a monoclonal band had been detected de novo. RESULTS: The
      incidence was 6.59 x 10(-4) year(-1). In 59.5% a diagnostic assumption was not
      stated. Most frequent diagnosis in the group of patients with a diagnosis was
      monoclonal gammopathy with uncertain meaning. Average age of patients was 74.4
      years and the difference between percentages by sex was statistically
      significant. DISCUSSION: The data suggest a lack of clinical effort when the
      result is the appearance of a monoclonal band. There is no discrepancy in the
      distribution of the bands and in the characteristics of the patients with regard
      to what is described in other studies.

PMID- 15970151
TI  - [Mental morbidity and social support in prisoners in treatment with
      antiretrovirals].
AB  - OBJECTIVE: To define the incidence of depressive disorders and anxiety disorders
      in prisoners of three prisons of CCAA in treatment with antiretrovirals, and
      moreover the associated variables and the intensity of social support within the
      prison. METHODS: Through a cross-sectional design 281 prisoners were studied.
      RESULTS: 42% showed mental morbidity and 53.4% lacked social support. To be
      imprisoned in the Granada prison, to be a woman, poor health state, to describe
      difficulties for compliance with antiretrovirals drug, a history greater than 13
      years for drugs consumption, and usual residence with the couple of family, all
      were factors associated with mental morbidity. Factors associated with social
      support non-existence were history of more than one imprisonment, lack of
      familiarity with the medical equipment, to be more than 35 years old, and to
      suffer mental morbidity.

PMID- 15970152
TI  - [Effectiveness of control of cardiovascular risk factors in type 2 diabetic
      population of Ciudad Real province].
AB  - BASIS: Diabetes mellitus type 2 has a very aggressive atherosclerosis profile,
      which means that the control of the cardiovascular risk factors should be very
      demanding. There are doubts concerning the attainment of such suitable objectives
      in primary care because of the difficulties for reproducing the conditions of
      clinical trials. METHODS: Observational, descriptive, cross-sectional, and
      multicenter study. It was designed in order to establish the level of control of
      principal risk factors (tobacco, hypertension, hyperglycemia, dyslipemia,
      obesity), and the use of aspirin, in type 2 diabetics cared in Primary Care
      centers in Ciudad Real province. 405 patients were evaluated by 33 physicians
      from 18 Primary Care centers. RESULTS: HbA1c values < 7% were obtained in 51.51%,
      45.9% of patients showed obesity, average glycemia was 163.61 +/- 51.47. Blood
      pressure < 130/85 was detected in 18.50% of patients, 62.22% of patients took
      some hypotensive drug and 51.20% antihypertensives. LDL-c < 100 mg/dl was
      detected in 10.21% but only 30.61% was on hypolipemic drugs. HDL-c was not
      determined in 26% of patients, and was 45 mg/dl in 66.44%. Aspirin was prescribed
      in 31.35%; 9.63% of patients were smoker. No patient reached all necessary
      prevention objectives. CONCLUSIONS: The control of the different risk factors in
      type 2 diabetics in Primary Care does not guarantee appropriate cardiovascular
      prevention. The behavior concerning to smoking was good in this study, and the
      levels of HDL-c and triglycerides were acceptable. Pharmacological treatment
      should have been most frequent and intense.

PMID- 15970153
TI  - [Current utilization of anticholinergics in the chronic obstructive pulmonary
      disease treatment].
AB  - Only 20% of patients with chronic obstructive pulmonary disease receive
      appropriate treatment. The most utilized among anticholinergics has been
      ipratropium bromide in inhalation very valued for its safety but that should be
      utilized every 6 hours. In these setting the average dose is 26% and when the
      patient takes de drug every 24 hours the dose index is 84%. Tiotropium is the new
      anti-cholinergic administered through respiratory airways that should be taken
      every 24 hours. It is more effective for improving functional residual capacity
      with levels much higher than ipratropium bromide. Furthermore, tiotropium is
      better than ipratropium bromide for improving the quality of life and for
      diminishing the frequency of exacerbations, one of the causes for improving the
      quality of life.

PMID- 15970154
TI  - [Multidisciplinary initiative for cerebrovascular stroke care improvement in
      Andalucia: PLACA project].
AB  - A comprehensive and integrating approach of all emergency medical teams implied
      in cerebrovascular attack (CVA) has been proposed within the framework of
      Emergencies Andalusian Initiative. Key action points were: the identification of
      CVA by emergency medical teams, the development of extrahospital care protocols
      for the patients up to diagnostic confirmation, the implementation of specific
      assistance teams, the use of trustworthy epidemiological information, and the
      development of a training (and information) plan for health professionals. A
      multidisciplinary group was set up in order to propose improvement actions
      applicable to these key points in the area of a public health system and,
      finally, a consensus document was written that constituted the basis for
      Andalusian Acute Stroke Initiative (PLACA project).

PMID- 15970155
TI  - [Antimalarials in systemic diseases].
AB  - Antimalarials are drugs known for more than 300 years. Most widely used
      antimalarials are chloroquine, hydroxychloroquine, and less commonly quinacrine.
      The mechanisms of action are various and incompletely defined in the present
      moment. Antimalarials are used in numerous autoimmune diseases, the most frequent
      of which are rheumatoid arthritis and lupus erythematous. These drugs benefit
      especially cutaneous and articular disease, and moreover they are helpful for
      improvement blood glucose, lipids, and platelet aggregation. We discuss the dose
      and the most common adverse effects, especially those related to retina.
      Attention is especially directed to the treatment of pregnant women.
      Antimalarials favorable effectiveness-toxicity proportion advises consider them
      in the management of autoimmune diseases.

PMID- 15970156
TI  - [Pharmacological treatment of depression].
AB  - Depression is a disorder with higher prevalence that generates important costs in
      the personal and socioeconomic fields. We have currently various antidepressants
      drugs for its treatment. In this article a review of these drugs is carried out,
      including various approaches necessary for addressing the special characteristics
      of each clinical situation. Pharmacological strategies for resistant depression
      are evaluated later. Finally, the future research lines are analyzed in order to
      improve the pharmacological depression treatment.

PMID- 15970157
TI  - [Medicine in images. Case 1: Pleuritic pain and peritoneal disease limited to
      left hypochondrium in a 58-year-old male].

PMID- 15970158
TI  - [Medicine in images. Case 2: Spectacular and early improvement of ventricular
      function after revascularization of hibernating myocardium].

PMID- 15970159
TI  - [Medicine in images. Case 3: A 27-year-old woman with eosinophilia and vena cava
      thrombosis].

PMID- 15970160
TI  - [Long arm terminal deletion of one of the 20 (46, XY, of the [20] [q11.2]
      [15]/46,XY) chromosomes pair and acute hybrid leukemia in a patient with fanconi
      aplastic anemia].

PMID- 15970161
TI  - [Lead poisoning: a forgotten etiology of abdominal pain].

PMID- 15970162
TI  - [Modulator role of p16ink4a in human papillomavirus infection].

PMID- 15970163
TI  - [Lysteria encephalitis associated to infliximab administration].

PMID- 15970164
TI  - [Comprehensive guidelines translate research findings into clinical policy for
      HIV-infected transplant candidates and recipients].

PMID- 15970165
TI  - [Prevalence of HIV-1-infection in dialysis units in Spain and potential
      candidates for renal transplantation: results of a Spanish survey].
AB  - INTRODUCTION: Patients with HIV infection and end-stage renal disease (ESRD) have
      improved their survival in the last few years. HIV infection is not considered a
      contradiction for renal transplantation, but little experience exists in renal
      transplantation in HIV infected individuals. There is no information about the
      prevalence of HIV infection in Spanish patients under renal replacement therapies
      (RRT). METHODS: A survey was performed in Spanish dialysis units during 2004. The
      objective was to study the prevalence and characteristics of HIV infection in
      patients under RRT in Spain. We also aimed to know how many of them met the
      Spanish criteria to be included on the renal transplantation waiting list.
      RESULTS: HIV prevalence was 1.15% (95%CI 0.85-1.45) of 4,962 patients who were
      under RRT, mostly under hemodialysis and, less commonly, peritoneal dialysis. The
      most frequent risk factor for HIV infection was parenteral drug use (58%). The
      most common causes of ESRD were glomerulonephritis (44%). The median time under
      RRT was 46 months. Coinfections with hepatitis C (60%) and B (7%) were found.
      Thirty-four percent of patients had a history of aids-defining events. Eighty-six
      percent were under HAART. The median CD4 cell count was 333 cells/.l and the
      viral load was undetectable in 68%. Of 40 patients with a completed clinical
      questionnaire, 9 (22.5%) met the Spanish criteria for renal transplantation.
      CONCLUSION: HIV prevalence in patients under RRT in Spain is 1.15% (0.85%-1.45%)
      and 22.5% percent of these patients met the Spanish criteria to be included on a
      renal transplantation waiting list.

PMID- 15970166
TI  - [Prevalences of hepatitis virus coinfection and indications for chronic hepatitis
      C virus treatment and liver transplantation in Spanish HIV-infected patients. The
      GESIDA 29/02 and FIPSE 12185/01 Multicenter Study].
AB  - INTRODUCTION: The aims of this study were to estimate the prevalence of HIV and
      hepatitis virus coinfection in the Spanish population and to determine the
      percentage of patients who are candidates for chronic hepatitis C virus (HCV)
      treatment and liver transplantation within this population. METHODS: A cross
      sectional study was performed in 2002 in two Spanish populations of HIV-infected
      patients: 1,260 patients from 39 centers throughout Spain (P1) and 1,560 patients
      from three tertiary teaching hospitals in Madrid (P2). RESULTS: The following
      hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV serological prevalence
      were found in the P1 and P2 groups, respectively: HAV-IgG antibodies: 74% and
      78%; HBsAg1: 4.9% and 4.8%; HBsAg-, anti-HBc1, anti-HBs1: 39% and 39%; HBsAg-,
      anti-HBc1, anti-HBs-: 25% and 31%; HBsAg-, anti-HBc-, anti-HBs1: 7% and 8%; HBsAg
      , anti-HBc-, anti-HBs-: 22% and 16%. Anti-HCV1: 61% and 65%, respectively. Of the
      patients with positive HCV serology, 88.8% and 84.6% of each group were positive
      for HCV-RNA by polymerase chain reaction. Multiple coinfections with hepatitis
      viruses were found in 3.2% and 2.8%, respectively; of these, 70% and 78% had
      coinfection with HBV, HCV and HDV. Liver cirrhosis was found in 5.8% and 9.6% of
      the patients coinfected with HIV and HCV, respectively. Liver transplant was
      indicated in approximately one out of every six coinfected patients with liver
      cirrhosis. The 43 and 37% of the HCV coinfected patients were good candidates for
      anti-HCV treatment, but only 14% and 15% of patients had initiated it.
      CONCLUSIONS: A high percentage of HIV-infected patients in Spain were coinfected
      with hepatitis viruses, especially HCV. The number of possible candidates for
      liver transplantation is rising and could increase in the next few years. In the
      future, greater efforts to treat HIV-and hepatitis virus-coinfected patients will
      be required.

PMID- 15970167
TI  - [Efavirenz and nevirapine plasma levels in HIV-infected patients with
      hemophilia].
AB  - The aim of this study was to evaluate efavirenz and nevirapine plasma levels in
      HIV-infected hemophilic patients seen in two hospitals in Barcelona. Plasma
      levels of these drugs were determined by high-performance liquid chromatography
      (HPLC) at four-month intervals, together with viral load and CD4 cell count.
      Nineteen patients treated with efavirenz and 8 with nevirapine were included, and
      68 efavirenz and 31 nevirapine determinations were performed. Mean study time was
      12 months. Median efavirenz plasma concentration was 2.95 .g/ml (interval: 1.54
      5.26 .g/ml) in patients with favorable virological response and 1.86 .g/ml (0.82
      4.88 .g/ml) in patients with detectable viral load (p = 0.32). Nevirapine plasma
      concentrations were 4.41 .g/ml (3.50-6.72 .g/ml) and 3.12 .g/ml (2.44-3.80 .g/ml)
      respectively (p = 0.18).

PMID- 15970168
TI  - [GESIDA/GESITRA-SEIMC, PNS and ONT consensus document on solid organ transplant
      (SOT) in HIV-infected patients in Spain (March, 2005)].
AB  - Solid organ transplant may be the only therapeutic alternative in some HIV
      infected patients. Experience in North America and Europe during the last five
      years shows that survival at three years after an organ transplant is similar to
      that observed in HIV-negative patients. The criteria agreed upon to select HIV
      patients for transplant are: no opportunistic infections (except tuberculosis,
      oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4
      lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver
      transplant) and an HIV viral load which is undetectable or suppressible with
      antiretroviral therapy. Another criterion is a two-year abstinence from heroin
      and cocaine, although the patient may be in a methadone programme. The main
      problems in the post-transplant period are pharmacokinetic and pharmacodynamic
      interactions between antiretorivirals and immunosuppressors, rejection and the
      management of relapse of HCV infection, which is one of the main causes of post
      liver transplant mortality. Up to now, experience with pegylated interferon and
      ribavirin is scarce in this population. The English version of the manuscript is
      available at http://www.gesidaseimc.com.

PMID- 15970170
TI  - [Renal transplantation in patients with HIV infection].
AB  - The prevalence of human immunodeficience virus (HIV) infection among patients
      under renal replacement therapy varies, with estimates of 1% for Europe and 1.5%
      for the United States. Survival in HIV infected individuals receiving renal
      replacement therapy has improved since the introduction of high activity
      antiretroviral therapy (HAART). Current experience in renal transplantation in
      HIV-infected patients in the United States indicates that the three-year survival
      rate is similar to that of HIV-negative transplant recipients, with virological
      and immunological control of the infection by HAART and no increase in the number
      of opportunistic infections or tumors. The criteria for selecting renal
      transplantation candidates in this population are the following: no aids-defining
      events, CD4 cells > 200 cells/.l and undetectable viral load under HAART. In
      Spain, where most of these patients are former drug abusers, a two-year period of
      abstinence from cocaine and heroine abuse is also required, although patients can
      be participating in the methadone program. The main problems in the post
      transplantation period have been interactions between HAART and immunosuppressive
      drugs, management of hepatitis C virus (HCV) coinfection and the high rate of
      acute rejection. To date, seven such renal transplantations have been performed
      in Spain, with favorable patient and graft survival and no progression to aids.

PMID- 15970171
TI  - [Ehrlichiosis and human anaplasmosis].
AB  - Human ehrlichiosis and anaplasmosis are acute febrile tick-borne diseases caused
      by various species of the genera Ehrlichia and Anaplasma (Anaplasmataceae). To
      date, only cases of human granulocytic anaplasmosis (HGA) caused by Anaplasma
      phagocytophilum (formerly human granulocytic Ehrlichia, Ehrlichia phagocytophila,
      and E. equi) have been diagnosed in Europe. HGA and Lyme borreliosis are closely
      related diseases that share vector and reservoirs. In addition to HGA, human
      monocytic ehrlichiosis caused by E. chaffeensis has been reported in North
      America, as well as cases of infection due to E. ewingii in immunocompromised
      hosts. Ehrlichia spp. and A. phagocytophilum have tropism for blood cells,
      especially leukocytes and platelets, causing a considerable decrease of both
      components in these patients. HGA should be suspected in tick-bitten patients or
      those who have visited an endemic area and show symptoms of flu-like fever,
      leukopenia and thrombocytopenia.

PMID- 15970172
TI  - [Subacute subdural empyema].

PMID- 15970173
TI  - [Fast-growing cervical mass and contralateral extrapleural mass in a patient with
      human immunodeficiency virus infection (HIV)].

PMID- 15970175
TI  - [Infective endocarditis due to Ochrobactrum anthropi].

PMID- 15970174
TI  - [Cerebral abscess due to Gemella haemolysans].

PMID- 15970176
TI  - [Pharmacokinetics/pharmacodynamics of the 1000/62.5 formulation of
      amoxicillin/clavulanic acid in odontostomatology].

PMID- 15970177
TI  - [Recurrent scarlet fever due to recent reinfection caused by strains unrelated to
      Streptococcus pyogenes].

PMID- 15970178
TI  - [Streptococcus agalactiae: antimicrobial sensitivity and macrolide-resistant
      genotypes in genital specimens from pregnant patients in Cantabria].

PMID- 15970179
TI  - [Evolution of a cohort of patients over 60 years old with HIV infection treated
      with highly-active antiretroviral therapy].

PMID- 15970180
TI  - [Tuberculous tenosynovitis in a patient with chronic corticosteroid therapy].

PMID- 15970181
TI  - [Interruption of antiretroviral therapy in chronically HIV-infected patients].
AB  - BACKGROUND AND OBJECTIVE: To describe the immunological, virological and clinical
      outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to
      identify the factors related to durability. PATIENTS AND METHOD: Retrospective
      study of patients who interrupt therapy after six months without clinical events,
      level of CD4+ > or = 500 cells/microl and HIV RNA > or = 5,000 copies/ml (3.7
      log10). RESULTS: In October 2004, 44 patients were included, 32 (72%) of them
      were stables after one year of ART cessation (group A) and 12 (28%) patients had
      to restart therapy due to a decreased CD4+ count < 300 cells/microl (group B).
      Both groups were compared. CD4 cell count nadir (414 cells/microl [199] versus
      171 cells/microl [107]; p = 0.000) and CD4+ count level at time of ART stop (920
      [302] cells/microl versus 633 cells/microl [177] p = 0.004) showed differences
      with statistical significance. The most important CD4+ count fall was observed at
      third month after stopping ART; 588 cells/microl (288) on group A and 382
      cells/microl (167) on group B. The mean time without ART was 27 months on group A
      and 7 months on group B. Two patients had acute retroviral syndrome, and one had
      Pneumocystis jiroveci pneumonia. Cholesterol levels were 199 mg/dl (42) and
      triglycerides 257 mg/dl (271) on ART and during interruption decreased to 155
      (38) and 165 (122) mg/dl respectively. After multivariate analysis, a CD4+ count
      nadir > 200 cells/microl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+
      count at time of ART stop > 800 cells/microl (p = 0,04; OR: 0,11; CI 95%: 0,015
      0,936) were independently related to durability of therapy interruption.
      CONCLUSIONS: Prolonged discontinuation of ART guided by CD4+ response causes a
      low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART
      cessation are protective factors of durability. An improvement of metabolic
      parameters is observed during the discontinuation of ART.

PMID- 15970182
TI  - [Waist circumference as a predictor of insulin resistance in young men].
AB  - BACKGROUND AND OBJECTIVE: Waist circumference (WC) is a measure of upper body fat
      and so should be useful for identifying overweight and obese men at risk of
      developing metabolic complications. The objective was to determine the relations
      of WC to cardiovascular risk factors in a sample of young men and to assess the
      clinical relevance of WC in identifying insulin resistance. SUBJECTS AND METHOD:
      This study included 194 male Spanish subjects aged 26 (5) years who were divided
      in 3 groups according to the WC: Normal (< 94 cm), moderate risk (> or = 94 cm)
      and elevated risk (> or = 102 cm). Body mass index (BMI), WC, blood pressure,
      serum levels of total cholesterol, triglycerides (TG), HDL-cholesterol, LDL
      cholesterol, glucose, uric acid and insulin were measured by standard methods.
      The homeostasis model assessment was applied to estimate the degree of insulin
      resistance (HOMAIR). RESULTS: The prevalence of overweight and obesity was 46.9%
      and 6.7% respectively. Men with moderate and elevated risk showed higher
      concentrations of glucose (p < 0.004), uric acid (p < 0.001), TG (p < 0.001), LDL
      cholesterol/HDL-cholesterol index (p < 0.001), insulin (p < 0.001) and HOMAIR (p
      < 0.001). WC was significantly correlated with age (r = 0,282; p < 0.001), TG (r
      = 0.308; p < 0,001), insulin (r = 0.282; p < 0.001) and HOMAIR (r = 0.281; p <
      0.001). A multivariate linear correlation analysis showed that HOMAIR was
      significantly associated with WC (p < 0.009) and TG (p < 0.003; r2 = 0.13).
      CONCLUSIONS: WC of these young men was independently associated with certain
      cardiovascular risk factors, in particular insulin resistance. This suggests that
      WC may be reasonably included in clinical practice as a simple tool that may help
      identify sub-groups of overweight or obese young men at higher metabolic risk.

PMID- 15970183
TI  - [Prevalence and risk factors of suspicion abuse in elder population].
AB  - BACKGROUND AND OBJECTIVE: We determined the prevalence and associated risk
      factors in the suspicion of elder abuse in the old population. PATIENTS AND
      METHOD: We included a total of 209 patients > or = 72 years of age without
      cognitive deterioration (score in test of Pfeiffer (3/4) 4 points). The
      questionnaire of suspicion of elder abuse used was one recommended by the
      Canadian Task Force and the American Medical Association; it consists of 9
      questions and the presence of a positive answer is considered as indicative of
      suspicion of abuse. RESULTS: The prevalence of suspicion of elder abuse was 52.6%
      (at least one positive answer to the questionnaire). 8.6% affirmatively responded
      to 2 questions and 2% to 3. Female gender, widowhood, deficiency of studies,
      living alone or in institutions and having exerted a remunerated work were the
      associated variables in the bivariant analysis with regard to the suspicion of
      abuse. In the model of logistic regression, there was a significant association
      with the civil status and the coexistence of the familiar nucleus, with a greater
      risk of elder abuse in unmarried and/or widowers (p < 0.001) and in those living
      alone (p < 0.0001). CONCLUSIONS: There is a high prevalence of suspicion of elder
      abuse in the old population.

PMID- 15970184
TI  - [Epidemiology of chronic hepatitis C virus in patients infected by human
      immunodeficiency virus. Study of 767 patients].
AB  - BACKGROUND AND OBJECTIVE: To study the epidemiological aspects of hepatitis C
      virus (HCV) infection in patients co-infected by human immunodeficiency virus
      (HIV). PATIENTS AND METHOD: This study was carried out in 767 HIV infected
      patients who were followed-up at the HIV/AIDS Unit of the Internal Medicine
      Department of the Arnau de Vilanova University Hospital of Lleida (Spain). In
      addition to clinical records and information about the probable contagion route,
      gender and starting year of intravenous drug use, patients were analyzed for the
      presence of hepatitis C antibodies, viral load and HCV genotype, alanine
      aminotransferase concentration, CD4+ lymphocytes and viral load of HIV. The stage
      of HIV infection was also recorded. RESULTS: 546 patients (71.18%) had antibodies
      to HCV, and 499 of them (91.39%) were intravenous drugs users. Of the HCV+
      patients, 61 (11.17%) seemed to have cleared the virus spontaneously. Commonest
      HCV genotype was 1 (52.57%), followed by 3 (25.56%) and 4 (18.76%). In patients
      with genotype 1, subtype 1a was the more frequent (65.49%) The variation of the
      genotypes according to the year of contagion showed a progressive increase of
      genotype-1 and a progressive decrease of genotype 3. The distribution of patients
      in the different clinics stages of HIV infection was homogeneous. CONCLUSIONS: In
      our health care area, most HIV+ patients, especially the intravenous drug users,
      are co-infected with HCV. Commonest genotype was 1 and commonest subtypes was 1a.

PMID- 15970185
TI  - [Waist circumference and metabolic and cardiovascular risk].

PMID- 15970186
TI  - [New goals for control of sexually transmitted diseases: role of centers of
      sexually transmitted diseases].

PMID- 15970187
TI  - [New treatments for chronic obstructive pulmonary disease].
AB  - Treatment of chronic obstructive pulmonary disease (COPD) has underwent a very
      important advance in the last five years. It has been developed a new long
      lasting anticholynergic drug, tiotrope bromure, which has been found to improve
      lung function and exercise capacity and to decrease relapses. Also the combined
      treatment of long lasting beta 2 adrenergics with inhaled steroids
      (salmeterol/fluticasone and formoterol/budesonide) has proven similar results.
      However, the response to these new drugs is not the same in all patients.
      Individual characteristics such as gravity, degree of bronchial
      hyperresponsiveness, frequency of relapses, comorbidity, etc will determine the
      response to several agents. Thus, it is necessary to perform a detailed
      diagnostic study in COPD patients in order to select the best treatment in an
      individualized form. In the future, new specific antiinflammatories such as
      phosphodiesterase 4 inhibitors or agents with a potential action in tissue
      regeneration could lead to new perspectives, as well as to new questions, in COPD
      treatment.

PMID- 15970188
TI  - [Levonorgestrel postcoital contraception: a sociodemographic study].

PMID- 15970189
TI  - [Major hemorrhages associated with long-term treatment with acenocoumarol in
      patients with venous thromboembolic disease in a rural area of Extremadura
      (Spain)].

PMID- 15970190
TI  - [Delayed prescription of antibiotics in Spain].

PMID- 15970191
TI  - [Medicine and television: a diagnosis history].

PMID- 15970192
TI  - [Interventional radiology as treatment of haematoma of the rectus abdominis].

PMID- 15970193
TI  - [Simultaneous description of the first two causes of hemoglobinopathy Korle-Bu in
      Spain].

PMID- 15970194
TI  - [Hashimoto's encephalopathy in a 20 years old patient].

PMID- 15970195
TI  - [Myocardial infarction and subacute intrastent thrombosis in a patient with
      aspirin resistance].

PMID- 15970197
TI  - Identification and purification of actin from the subpellicular network of
      Toxoplasma gondii tachyzoites.
AB  - Toxoplasma gondii infects cells through dynamic events dependent on actin.
      Although the presence of cortical actin has been widely suggested, visualisation
      and localisation of actin filaments has not been reported. The subpellicular
      cytoskeleton network is a recently described structure possibly involved in the
      dynamic events. Using non-ionic detergent extractions, the cortical cytoskeleton
      network was enriched and used for the isolation and identification of actin.
      Actin was detected by Western blots in extracts of cytoskeleton networks, and it
      was localised by gold staining in the network and in both the apical end and the
      posterior polar ring. Actin was isolated from subpellicular cytoskeleton extracts
      by binding to DNase I, and it polymerised in vitro as filaments that were gold
      decorated by a monoclonal anti-actin antibody. Filaments bound the subfragment 1
      of heavy meromyosin, although with atypical arrangements in comparison with the
      arrowheads observed in muscle actin filaments. Treatment with cytochalasin D and
      colchicine altered the structural organisation of the subpellicular network
      indicating the participation of actin filaments and microtubules in the
      maintenance of its structure. Actin filaments and microtubules, in the
      subpellicular network, participate reciprocally in the maintaining of the
      parasite's shape and the gliding motility.

PMID- 15970198
TI  - Influence of body segments' parameters estimation models on inverse dynamics
      solutions during gait.
AB  - The purpose of the present study was to examine the influence of anthropometric
      data on joint kinetics during gait. We particularly focused on the sensitivity of
      inverse dynamics solutions to the use of models for body segment parameters (BSP)
      estimation. Six often used estimation models were selected to provide BSP values
      for the three segments of the lower limb. Kinematics and dynamics were sampled
      from seven subjects performing barefoot gait at three different speeds. Joint
      kinetics were estimated with the bottom-up method using BSP values derived from
      each estimation model as anthropometric inputs. The BSP estimates were highly
      sensitive to the model used with deviations ranging from at least 9.73% up to
      60%. Maximal variations of peak values for the hip joint flexion/extension moment
      during the swing phase were 20.11%. Hence, our findings suggest that the
      influence of BSP cannot be neglected. Observed deviations are especially due to
      the effect of varying simultaneously the mass, moments of inertia and the center
      of mass location values, according to the underlying relationship of
      interdependency linking each component. Considering both the differences found in
      joint kinetics and the level of accuracy of BSP models, evidence is provided that
      using multiple regression BSP estimation functions derived from Zatsiorsky and
      Seluyanov should be recommended to assess joint kinetics.

PMID- 15970199
TI  - Obstruction identification in branching compliant tubes with application to
      airway passages.
AB  - A feasibility study for occlusion identification in a branched tube-like
      structure using the frequency spectrum of the acoustic input impedance determined
      at the main entrance to the network is presented. The frequency spectra for one-
      and two-generation models are generated to study the effect of an occlusion in
      one of the branches on the spectra with an application to the trachea and the
      first two generations of the airways. The result demonstrates that the input
      impedance resonant frequencies can map the location, severity and degree of an
      obstruction in any of the considered branches.

PMID- 15970200
TI  - Assessment of compressive modulus, hydraulic permeability and matrix content of
      trypsin-treated nucleus pulposus using quantitative MRI.
AB  - A clinical strength MRI and intact bovine caudal intervertebral discs were used
      to test the hypotheses that (1) mechanical loading and trypsin treatment induce
      changes in NMR parameters, mechanical properties and biochemical contents; and
      (2) mechanical properties are quantitatively related to NMR parameters. MRI
      acquisitions, confined compression stress-relaxation experiments, and biochemical
      assays were applied to determine the NMR parameters (relaxation times T1 and T2,
      magnetization transfer ratio (MTR) and diffusion trace (TrD)), mechanical
      properties (compressive modulus H(A0) and hydraulic permeability k(0)), and
      biochemical contents (H(2)O, proteoglycan and total collagen) of nucleus pulposus
      tissue from bovine caudal discs subjected to one of two injections and one of two
      mechanical loading conditions. Significant correlations were found between k(0)
      and T1 (r=0.75,p=0.03), T2 (r=0.78, p=0.02), and TrD (r=0.85, p=0.007). A trend
      was found between H(A0) and TrD (r=0.56, p=0.12). However, loading decreased
      these correlations (r=0.4, p=0.2). The significant effect of trypsin treatment on
      mechanical properties, but not on NMR parameters, may suggest that mechanical
      properties are more sensitive to the structural changes induced by trypsin
      treatment. The significant effect of loading on T1 and T2, but not on H(A0) or
      k(0), may suggest that NMR parameters are more sensitive to the changes in water
      content enhanced by loading. We conclude that MRI offers promise as a sensitive
      and non-invasive technique for describing alterations in material properties of
      intervertebral disc nucleus, and our results demonstrate that the hydraulic
      permeability correlated more strongly to the quantitative NMR parameters than did
      the compressive modulus; however, more studies are necessary to more precisely
      characterize these relationships.

PMID- 15970201
TI  - Effects of lengthening the speech signal on auditory word discrimination in
      kindergartners with SLI.
AB  - In the present study, it was investigated whether kindergartners with specific
      language impairment (SLI) and normal language achieving (NLA) kindergartners can
      benefit from slowing down the entire speech signal or part of the speech signal
      in a synthetic speech discrimination task. Subjects were 19 kindergartners with
      SLI and 24 NLA controls. Results showed both types of speech manipulation to
      positively influence word discrimination for the entire group of children.
      Further analysis made clear that the effects were due to the improvement of the
      scores of the lowest 25% scorers (8 SLI, 3 NLA). LEARNING OUTCOMES: As a result
      of this activity, the reader will be able to: (1) give an overview on the effects
      of speech manipulation on discrimination abilities of children with SLI, (2) be
      able to look with more nuance at the reported effects of the FFW software
      program.

PMID- 15970202
TI  - An ergonomic evaluation of manual Cleco plier designs: effects of rubber grip,
      spring recoil, and worksurface angle.
AB  - The present study evaluated two design modifications (rubber grip and torsion
      spring) to the conventional manual Cleco pliers by electromyography (EMG), hand
      discomfort, and design satisfaction. This study also surveyed workers'
      satisfaction with selected design features of the pliers for ergonomic
      improvement. A two-way (plier design x worksurface angle) within-subject (nested
      within gender and hand size) design was employed. Eleven workers simulated the
      plier task in an adjustable workstation for different plier designs and
      worksurface angles (0 degrees , 60 degrees , and 90 degrees ). Lower EMG values
      were obtained for the pliers with rubber grip and at 60 degrees of worksurface
      angle. EMG values varied significantly between the participants, but showed low
      correlations (Spearman's rank correlation = -0.27 approximately -0.58) with their
      work experience with the pliers. The hand discomfort and design satisfaction
      evaluations identified that the grip span (max = 14.0 cm) and grip force
      requirement (peak = 220.5 N) of the current pliers need ergonomic modification.
      The present study shows the needs of both the ergonomic design of a hand tool and
      the training of a proper work method to control work-related musculoskeletal
      disorders at the workplace.

PMID- 15970203
TI  - Development and validation of a novel portable slip simulator.
AB  - The objective was to develop, construct and validate a portable device suitable
      for measurements of pedestrian slip resistance in situ. The developed device
      proved to be precise enough and easy to use. The dynamic coefficient of friction
      (DCOF) values measured by it showed strong correlation (r> or = 0.990, p < 0.001)
      with the values measured by the force platform used as a reference. In addition,
      the measured DCOF values were in good consistency with those obtained when using
      the older laboratory device of the Institute, the slip simulator. Based on the
      use of the new, developed device it can be concluded that accurate friction
      measurements with actual footwear can be performed even with a moderate-sized but
      portable device. The developed slipmeter will be used to measure slipperiness of
      various walking surface conditions, e.g. at different work places and in
      walkways, in the near future.

PMID- 15970204
TI  - Does a rolling floor reduce the physical work demands and workload, and increase
      the productivity of truck drivers handling packed goods?
AB  - A PCM rolling floor (RF) was developed to reduce the risk of musculoskeletal
      complaints among truck drivers. The RF can be used to move packed goods
      automatically in and out of the cargo space. The efficacy of this intervention on
      physical work demands, energetic and perceived workload and productivity was
      evaluated by comparing nine truck drivers working with a RF and a traditional,
      non-moving floor during a working day. Since the RF was not used during the
      loading process, no effects were found. The RF reduced the unloading process by 8
      min, decreased the frequency of lifting and setting down goods by 24%, decreased
      the frequency of handling goods below knee level by 79%, and decreased the
      frequency of entering the cargo space by 45%. No effect was found on the
      energetic and perceived workload. The RF resulted in a small increase in
      productivity.

PMID- 15970205
TI  - Factors affecting stepladder stability during a lateral weight transfer: a study
      in healthy young adults.
AB  - A fall from a stepladder is often initiated by a loss of lateral stability. An
      inverted pendulum model of the human, validated by experiment, was used to
      determine the feasible range of whole-body center of mass (COM) states for which
      weight can be transferred laterally on a ladder tread without a ladder rail
      losing contact with the ground ("no lift-off" stability region). The results show
      that the size of the feasible no lift-off region was inversely proportional to
      the height of the tread above the ground, the distance of the stance foot from
      the ipsilateral rail, and lateral ground inclination angle. For given initial COM
      kinematics on a tread height equal to 40% human body height, a stance-foot
      location equal to one-eighth tread width and a 3.5 degrees ground inclination had
      approximately equivalent effects on the no lift-off region size. Ladder stability
      was three times more sensitive to tread height than to foot location. Laterally
      exerted impulsive hand-tool forces should generally be limited to 8% body weight.
      These findings can lead to improved ladder designs and safety instructions for
      stepladder users.

PMID- 15970206
TI  - Ergonomic redesign and evaluation of a clamping tool handle.
AB  - The handle of a commercial bar clamp was redesigned using ergonomic principles
      and then compared with an original clamp. Ten male and ten female students
      participated in simulated clamping tasks under various conditions, including
      different clamping heights, clamping methods, and handle-gripping methods, with
      respect to the dependent variables of clamping and handle-squeezing forces. The
      results showed that the redesigned clamp produced larger clamping force with
      lower handle-squeezing forces than the original clamp. As expected, males exerted
      more force than females in both clamping and squeezing forces. A pistol grip
      method was superior to an upside-down handle-gripping method. Two-handed
      operation was recommended for this type of clamp by simultaneously pulling the
      trigger and sliding the bar in order to initially tighten around objects. This
      study shows that the application of ergonomic guidelines increases the efficiency
      and usability of manual handtools.

PMID- 15970207
TI  - Sodium-phosphate cotransporter in human salivary glands: molecular evidence for
      the involvement of NPT2b in acinar phosphate secretion and ductal phosphate
      reabsorption.
AB  - OBJECTIVE: In order to elucidate the cellular and molecular mechanisms of
      phosphate secretion by human salivary glands, the expression and intracellular
      distribution of sodium-phosphate cotransporters was investigated. DESIGN: Total
      RNA was extracted from 33 parotid gland (PG) and 35 submandibular gland (SMG)
      samples and RT-PCR was performed using gene specific primers for all known sodium
      phosphate cotransporters. An antibody was raised against an NPT2b epitope and the
      cellular and intracellular distribution was investigated by immunohistochemistry.
      RESULTS: No mRNA for the type I cotransporter NPT1 was found. Out of the type II
      phosphate cotransporters only message for NPT2b but not for NPT2a or NPT2c could
      be detected in about the same number of samples (76% in PG versus 69% in SMG).
      Type III cotransporter mRNA was also found in both glands, PIT1 gave positive
      results for 93% of PG samples compared to 69% of SMG samples. For PIT2 also, a
      higher expression was found in PG than in SMG, although the difference was
      smaller (79% versus 51%). Immunostaining for NPT2b was found both in the acini
      and in the ducts, with a stronger reaction in the latter. In acinar cells, NPT2b
      was restricted to the basal-lateral plasma membrane, in duct cells, a broad band
      of reactivity was located in the apical part of the cell. CONCLUSIONS: These
      findings suggest a secondary active secretion of phosphate into the primary
      saliva. Ductal cells appear to be able to reabsorb phosphate, thereby modifying
      the phosphate concentration in the final saliva.

PMID- 15970208
TI  - Organic secretory products, adaptive responses and innervation in the parotid
      gland of ferret: a histochemical study.
AB  - To qualify cellular events of possible pathophysiological significance in the
      parotid of ferret, tissue obtained post-mortem from mature animals of either sex
      was examined by light microscopical histochemistry for calcium, protein, amino
      acids, mucosubstances and hydrolases, and by neurohistology. Calcium was
      localised in acinar cells replete with granules containing protein, disulphides
      and usually carboxylated mucosubstances. Acid phosphatase activity was basally
      concentrated in the acinar cells. The granular luminal region of striated ductal
      cells showed protein, tryptophan, disulphides, neutral mucosubstances, and E600
      sensitive esterase and Naphthol AS-D chloroacetate esterase activities, whereas
      their basal region showed acid phosphatase activity. Strong periluminal activity
      of acid phosphatase and E600-resistant esterase characterised the collecting
      ducts. Cholinesterase activity was associated with an extensive network of nerve
      fibres embracing parenchyma. Catecholamine fluorescence was not seen. beta
      glucuronidase reactive macrophages abounded in the interstices. The results
      suggest that while the acini in the parotid of ferret secrete polyionic
      glycoproteins, shielded by calcium, the striated ducts secrete tryptophan-rich
      products comprising neutral glycoproteins and showing proteolytic activity.
      Innervation is of the cholinergic type and parenchymal lysosomal activity,
      possibly related to autophagy of stored secretory products and heterophagy of
      luminal material, is brisk. Macrophages contribute to maintaining the glandular
      microenvironment, wherein secretory activity appears to be lethargic.

PMID- 15970209
TI  - Variation in bacterial DGGE patterns from human saliva: over time, between
      individuals and in corresponding dental plaque microcosms.
AB  - OBJECTIVE: Eubacterial 16S rDNA fingerprints of human saliva and dental plaque
      microcosm biofilms grown in the multi-plaque artificial mouth (MAM) were
      characterised using denaturing gradient gel electrophoresis (DGGE). DESIGN: The
      stability of the bacterial community in the saliva of one individual collected
      over 7 years was assessed and compared with bacterial patterns in the saliva of
      10 different individuals. DGGE was also used to assess changes in bacterial
      composition between saliva and mature plaque microcosms developed in the MAM from
      these 10 individual saliva samples. RESULTS: A relatively stable bacterial
      community (>87% concordance) was maintained within the individual oral
      environment of the standard donor over 7 years of monitoring. By comparison, DGGE
      fingerprint patterns of saliva from 10 different donors displayed greater
      variability (66% concordance). Variability between individual DGGE profiles
      increased further in mature plaque microcosms grown from the saliva of the 10
      donors (52% concordance) with an increase in detected species diversity and
      evidence for conserved similarity and hence the maintenance of organisation
      during community development. CONCLUSIONS: These results suggest that stable
      ecological conditions were maintained long-term within the oral environment of
      the individual saliva donor but that transient fluctuations also occurred. The
      ecology and predominating microbiota in different individuals was host-specific
      and these differences were maintained to a degree during development into mature
      plaque microcosms. These findings also demonstrate the potential usefulness of
      applying DGGE to monitor temporal and developmental changes and possibly
      pathogenic patterns in oral bacterial communities from saliva and plaque.

PMID- 15970210
TI  - Antisense inhibition of transglutaminase 2 affects development of mouse embryo
      submandibular gland in organ culture.
AB  - Tissue transglutaminase (TGase 2) has been implicated in numerous cellular
      functions, i.e., apoptosis, differentiation, extracellular matrix protein cross
      linking and organogenesis. Earlier report of the strong transient expression of
      TGase 2 localized at the anchoring sites of muscle bundles of human embryo and
      recent findings of a similar transient expression of the TGase 2 in the salivary
      myoepithelial cells of mouse embryo indicated a definitive role of TGase 2 in the
      cytodifferentiation of myoepithelial cells. To understand functional role(s) of
      TGase 2 in the organogenesis of salivary gland, antisense inhibition of TGase 2
      expression was performed in the organ culture of mouse embryo submandibular
      gland. The antisense of TGase 2 transfection tested using oral keratinocyte cell
      line, KB cells, elicited significant inhibition of cellular transglutaminase
      expression. The same antisense treatment of submandibular glands in organ culture
      also resulted in the suppression of cellular TGase 2 expression as indicated by
      weak immunoreaction against anti-TGase 2 in the myoepithelial cells of
      submandibular glands in contrast to strong reaction in those of the normal and
      sense-treated glands. Antisense to TGase 2 treatment induced retarded growth of
      salivary epithelium in 1 week and severe aberrant growth of salivary ducts and
      acini in 2 weeks and also expression of apoptotic inducer, Bax specifically
      localized in the myoepithelial cells, suggesting apoptotic state of myoepithelial
      cells. These data suggest that the antisense inhibition of TGase 2 expression
      affects the cytodifferentiation of ductal cells and myoepithelial cells, and
      resulted in severe retardation of tubuloalveolar structure formation of salivary
      gland.

PMID- 15970211
TI  - Association of bovine dentine phosphophoryn with collagen fragments.
AB  - Bovine dentine phosphophoryn (BDP), a protein rich in aspartyl (Asp) and O
      phosphoseryl (Ser(P)) residues, is synthesized by odontoblasts and believed to be
      involved in matrix-mediated biomineralization of dentine. Phosphophoryn was
      purified from bovine dentine using EDTA extraction, Ca(2+) precipitation, anion
      exchange and size exclusion chromatography. The purified protein migrated on SDS
      PAGGE as a single band. The protein was dephosphorylated using a chelex alkaline
      dialysis procedure, repurified using anion exchange and size exclusion
      chromatography and then subjected to cleavage with trypsin. The digest was
      subjected to reversed-phase HPLC and analysed by Q-TOF mass spectrometry. The
      only non-trypsin peptides that could be identified were two collagen Type I
      alpha2 peptides whose sequence was determined by fragmentation analysis. The
      association of collagen fragments with highly purified phosphophoryn suggests
      that the EDTA extraction method yields BDP that is strongly bound to collagen
      fragments. This association now helps explain discrepancies in molecular weight
      and amino acid composition data for various phosphophoryn preparations compared
      with the same data calculated from the C-terminal extension of mouse, rat and
      human dentine sialophosphoprotein (DSPP) gene products. Analysis of the mutation
      pattern of the clinical disorder Osteogenesis Imperfecta within the region
      enclosed by the identified collagen fragments reveals that phosphophoryn
      associates with a segment of collagen that is crucial for structure and/or
      function.

PMID- 15970212
TI  - Lysozyme activity in the initially formed in situ pellicle.
AB  - Lysozyme is one of the most abundant enzymatic components in the salivary
      pellicle. The purpose of the present in situ study was to determine if and to
      which extent lysozyme immobilised in pellicles exposes enzymatic activity.
      Influence of different oral sites and pellicle formation time on enzyme activity
      was also evaluated. Bovine enamel slabs (5mm diameter) were fixed on buccal and
      oral sites of individual trays worn by six subjects for 3 and 30 min on different
      days. After pellicle formation, slabs were removed from the trays and rinsed with
      running water. Afterwards, pellicle-bound lysozyme activity was determined via
      lysis of Micrococcus lysodeicticus photometrically in two steps. In a first step,
      lysozyme was desorbed in phosphate buffer and dissolved activity was measured. In
      a second step, slabs were incubated in phosphate buffer with the substrate and
      remaining immobilised activity was determined. All investigated pellicles
      exhibited lysozyme activity. Great intra- and inter-individual differences were
      observed. Mean desorbed activity of 3 min-pellicles amounted to 26.06+/-17.81
      U/cm(2) (30 min; 26.79+/-17.48). The remaining immobilised activity was 13.54+/
      11.42 for 3 min-pellicles and 16.08+/-12.81 for 30 min-pellicles. Pellicle
      derived lysozyme showed a Michaelis type kinetic. CONCLUSION: In situ pellicle
      exposes lysozyme activity even after a 3 min formation period. Exposed enzyme
      activity is neither influenced by pellicle formation time nor by the site of
      pellicle formation. It shows great inter- and intra-individual differences.

PMID- 15970213
TI  - Cell kinetics of mechanically stimulated rat oral epithelia.
AB  - OBJECTIVE: To study cell kinetics of rat gingival (GE), sulcular (SE) and
      junctional (JE) epithelia in the steady-state and after application of mechanical
      pressure. DESIGN: Elastic bands were inserted between first and second maxillary
      molars of 8-week-old male rats, which were labelled with H(3) TdR and killed in
      groups of six to seven animals together with equal-sized groups of labelled
      control animals at intervals between 1 and 168 h. Autoradiographs were used to
      determine epithelial cell proliferation on the pressure side of M1 by calculating
      the percentage of (3)H TdR-labelled cells (PLC) in the basal (BL) and suprabasal
      (SL) layers of GE, SE and JE and to estimate median cell cycle (MCC) duration of
      BL cells by plotting mean and median grain counts against time. RESULTS: (3)H TdR
      labelled cells were present in SL of SE and JE 1-12h after isotope injection
      suggesting that the BL might be not the only source of progenitor cells for JE as
      they might also be derived through migration from adjacent SE. Application of
      pressure significantly (ANOVA, P<0.05) reduced PLC in BL of GE, SE and JE
      indicating a decrease of cell proliferation after 1-12h in response to pressure.
      In steady-state, the MCC durations of BL cells of GE, SE and JE were 39, 14 and
      9h, respectively. After application of pressure, they increased significantly
      (chi(2)-test, P<0.05) to 48, 44 and 34 h, respectively. CONCLUSIONS: Sustained
      pressure may lead to reduction of proliferative activity of these epithelia
      inducing slower progression of progenitor cells through the cell cycle.

PMID- 15970214
TI  - Assessing combination treatments in acute stroke: preclinical experiences.
AB  - BACKGROUND: Acute ischemic stroke is a complex disease. Treatment success may
      require combining different therapeutic approaches. An obvious treatment
      combination in acute ischemic stroke is a thrombolytic therapy, adjuvant with a
      neuroprotective agent to have better stroke recovery. SUMMARY OF REVIEW: Complete
      factorial designs can assess the synergy of combination treatments and
      distinguish them from supper-additive, additive or sub-additive effects. A
      factorial design, a two-way analysis of variance and a novel graphic technique
      can detect and illustrate interactions of two treatments, which were used to
      evaluate combination treatments to extend the therapeutic window for thrombolytic
      therapy in an embolic stroke model on rats. We hypothesized synergy or additive
      effects on stroke recovery when combining thrombolytic therapy with either an
      antagonist to the integrin CD11b/CD18 (UK-279,276) or a glycoprotein IIb/IIIa
      receptor inhibitor. CONCLUSIONS: Factorial designs offer an efficient approach to
      study synergistic effects of two treatments. Our graphical technique provides a
      powerful, intuitive and quantitative explanation of joint treatment effects.
      Combining thrombolytic therapy with a neuroprotectant yielded a super-additive or
      additive treatment effect for two preclinical experiments designed to extend the
      thrombolytic therapeutic window for stroke.

PMID- 15970215
TI  - Altered behavioural response to acute stress in mice lacking cellular prion
      protein.
AB  - Although many studies have investigated the function of cellular prion protein
      (PrPc), its physiologic role remains elusive. PrPc null mice have been reported
      to develop normally and to show normal performance in most behavioural tests. In
      the present study we investigated whether this also holds true after episodes of
      acute stress. PrPc gene ablated (Prnp0/0) and wild-type mice were subjected to
      restraint stress, electric foot shock, or swimming and compared with non-stressed
      animals. Immediately after the stressful situation, the anxiety levels and
      locomotion of the animals were measured using plus-maze and open-field tests.
      Among non-stressed animals, there was no significant difference in performance
      between Prnp0/0 and wild type animals in either test. However, after acute stress
      provoked by a foot shock or a swimming trial, Prnp0/0 animals showed a
      significant decrease in anxiety levels when compared with control animals.
      Moreover, after the swimming test, knockout mice presented decreased locomotion
      when compared to wild-type mice. Because of this observation, we also assessed
      both types of mice in a forced swimming test with the objective of better
      evaluating muscle function and found that Prnp0/0 animals presented reduced
      forced swimming capacity when compared to controls. As far as we know, this is
      the first report suggesting that cellular prion protein is involved in modulation
      of anxiety or muscular activity after acute psychic or physical stress.

PMID- 15970216
TI  - Early weaning deprives mouse pups of maternal care and decreases their maternal
      behavior in adulthood.
AB  - Weaning is one of the most important events in the early stage of life, and
      recently we have found that precocious weaning augments anxiety and
      aggressiveness in mice. Maternal behavior has been reported to be transmitted
      from one generation to the next; that is, female pups that received intensive
      maternal care showed higher maternal behavior in their adulthood. In the present
      study, the following three experiments were conducted to understand maternal
      behavior transmission in early-weaned mice that were separated from the dam on
      postnatal day 14. First, the maternal behavior observed from the postpartum day
      15 to 21, which was deprived in the early-weaned mice, were analyzed. Mothers
      spent 3% of their time on licking/grooming and arched-back nursing of their pups
      on postpartum day 15, and the time spent on these behaviors was gradually
      decreased until postpartum day 21; however, they spent 50% of their time
      attending to their pups through postpartum days 15-21. Simultaneously, the
      behavior of the pups was monitored, and it was found that the early-weaned mice
      had higher activity and lower resting behavior over the period from postnatal day
      15 to 21. Secondly, the early- and normally weaned female mice were subjected to
      an elevated plus maze test at the age of 8 weeks to assess their anxiety level.
      The early-weaned mice showed a lower frequency of entering the open arms, and a
      shorter duration of time spent within them, as compared to the normally weaned
      mice, suggesting that early-weaned females had a higher anxiety level. In the
      third experiment, the two groups of female mice were paired with adult male mice
      for 2 weeks, and the mother's maternal behavior was analyzed. The early-weaned
      female mice showed lower frequency of licking/grooming and arched-back nursing of
      their pups as compared to the normally weaned mice, whereas the time of mother
      off pups and attending to pups were not different between groups. These results
      suggest that early-weaning manipulation deprives offspring of a certain level of
      maternal care, and as a consequence, the offspring show higher anxiety levels and
      lower maternal behavior in their own adulthood.

PMID- 15970217
TI  - Behavioural effects of parafascicular thalamic lesions in an animal model of
      parkinsonism.
AB  - We recently reported that the centromedian-parafascicular thalamic complex (CM
      Pf) degenerates in Parkinson's disease and progressive supranuclear palsy. The
      contribution of such thalamic pathology to disease symptoms has not yet been
      established. The present study therefore investigated the behavioural impact of
      lesioning the corresponding thalamic region (termed Pf) on a range of behaviours
      present in rodents. There were four surgical groups: (1) sham medial forebrain
      bundle (mfb)+sham Pf, (2) 6-OHDA mfb lesion+sham Pf, (3) sham mfb+NMDA Pf lesion,
      (4) 6-OHDA+NMDA Pf lesions. Posture, sensory functions and apomorphine-induced
      rotational asymmetry were assessed before and after each surgery. Other
      assessments performed including a timed motivational task, grooming behaviours
      and piloerection. 6-OHDA lesions induced postural (ipsilateral curling and head
      position biases), sensorimotor (increased latency to respond to tactile
      stimulation of the contralateral side when eating or grooming) and rotational
      abnormalities (contralateral circling after apomorphine). The main effects of
      combined 6-OHDA+Pf lesions were improved performance in a motivational task
      (decreased latency to retrieve reward) but worsened piloerection, relative to
      animals with either 6-OHDA or Pf lesions alone. The thalamic zone common to all
      lesioned animals involved the posterior Pf. Our data suggests that the posterior
      CM-Pf may be involved in motivational responses and autonomic dysfunction in
      parkinsonian disorders.

PMID- 15970218
TI  - Latent inhibition is disrupted by nucleus accumbens shell lesion but is
      abnormally persistent following entire nucleus accumbens lesion: The neural site
      controlling the expression and disruption of the stimulus preexposure effect.
AB  - Latent inhibition (LI) is the proactive interference of repeated nonreinforced
      preexposure to a stimulus with subsequent performance on a learning task
      involving that stimulus. The present experiments investigated the role of the
      nucleus accumbens (NAC) in LI. LI was measured in a thirst motivated conditioned
      emotional response procedure with low or high number of conditioning trials, and
      in two-way active avoidance procedure with the stages of preexposure and
      conditioning taking place in the same or different contexts. Sham-lesioned rats
      showed LI with low but not high number of conditioning trials and if preexposure
      and conditioning took place in the same context but not if the context was
      changed between the stages. Lesion to the shell subregion of the NAC disrupted LI
      but LI was preserved in rats with a combined lesion to the NAC shell and core
      subregions. Moreover, rats with a combined shell-core lesion persisted in showing
      LI in spite of high number of conditioning trials and in spite of context change.
      These results show that the NAC is not essential for the acquisition of LI but
      rather plays a key role in regulating the expression of LI. Moreover, they
      suggest that the two subregions of the NAC contribute competitively and
      cooperatively to this process, selecting the response appropriate to the stimulus
      no event or the stimulus-reinforcement association in conditioning.

PMID- 15970219
TI  - On the feasibility to detect and to quantify prepulse-elicited reaction in
      prepulse inhibition of the acoustic startle reflex in humans.
AB  - The possibility that the prepulse stimulus typically employed in the studies of
      prepulse inhibition (PPI) can produce observable response has been questioned
      recently. Conflicting reports range from observations of prepulse-elicited
      startle reaction to a complete lack of detectable prepulse-elicited reactions in
      healthy volunteers. This controversy is subjected to critical examination in the
      present study. The ability of prepulse stimuli to induce PPI and to elicit
      measurable responses was examined in two separate experiments using prepulses
      ranging from 6 to 18dB above background (experiment 1), or 1 to 5dB above
      background (experiment 2). Three levels of pulse stimulus were employed: 95, 105
      and 115dBA. Clear PPI and prepulse-elicited reaction were obtained in experiment
      1, while neither effect was evident in experiment 2. Non-startle-eliciting
      prepulses that are of sufficient intensities to induce reliable PPI are
      associated with detectable and quantifiable response, confirming that direct
      evaluation of prepulse-processing is feasible and practical. This provides an
      additional measure of theoretical and potentially clinical relevance to PPI, and
      it ought to be included in future studies in patients as well as healthy
      subjects.

PMID- 15970220
TI  - Effects of excitotoxic thalamic intralaminar nuclei lesions on attention and
      working memory.
AB  - In rats, lesions of the thalamic intralaminar nuclei (ILn) impair measures of
      working memory, but it is unclear whether alterations of attention contribute to
      the mnemonic deficits. The present experiment tested the effects of ILn lesions
      on a two-lever attention task that required discrimination of visual signals and
      non-signals. Rats were trained presurgically in the task and then received sham
      surgery or infusions of n-methyl-d-aspartate (NMDA) into the ILn to induce
      excitotoxic lesions. ILn lesions transiently decreased accurate detection of
      signals. ILn lesions also increased omissions. Compared to sham-lesioned rats,
      ILn-lesioned animals were not differentially affected when task demands were
      increased by presenting a visual distracter. Finally, a retention interval was
      incorporated into the task to assess whether the lesions affected acquisition of
      a working memory version of this behavioral paradigm. Unlike sham-lesioned
      animals, ILn-lesioned rats did not demonstrate a significant improvement in
      signal detection when a retention interval was introduced. The transient lesion
      induced deficits in the attention task suggest that, in rats, the ILn may
      contribute to aspects of attentional processing, but through neural re
      organization or activity in other regions, there is compensation for the loss of
      ILn functioning. The ILn appear to be necessary for maintaining performance when
      working memory demands are increased.

PMID- 15970221
TI  - Behavioral and cognitive profile of mice with high and low exploratory
      phenotypes.
AB  - Temperament is the heritable and relatively stable pattern of basic emotions,
      such as fear and anger. We explored behavioral features in mice to select
      distinct phenotypes with extremes of temperament. In a new environment (open
      field) with a central object, two groups of 15 mice from 79 screened were
      separated according to high or low exploration of the object to compose the high
      and low exploratory groups, respectively. Their performance was mostly identical
      in the same task 1 week later and still distinguishable 8 months later,
      suggesting the presence of trait or temperamental features. These mice were
      further tested in other behavioral tasks. Compared to low exploratory mice, high
      exploratory mice were less anxious in the light/dark task and the elevated plus
      maze, showed increased locomotion in an open-field, improved their performance
      along trials in the Lashley maze (with appetitive stimulus) and had higher
      latency to step-down in the inhibitory avoidance task (with aversive stimulus).
      High exploratory mice were aggressive in the intruder test, whereas low
      exploratory mice were non-aggressive or submissive. These results show that
      individual differences in temperament influence a range of behaviors in mice. The
      behavioral profile of low and high exploratory mice resembled the depressive and
      hyperthymic temperaments of patients with unipolar depression and bipolar
      disorders, respectively, which may be relevant for modeling mood disorders.

PMID- 15970222
TI  - Expression of egr-1 (zif268) mRNA in select fear-related brain regions following
      exposure to a predator.
AB  - Research has demonstrated that immediate-early genes/inducible transcriptional
      factors (e.g., c-fos, egr-1) are increased in amygdala nuclei (lateral, basal and
      central nuclei) known to be involved in fear conditioning, footshock stress and
      novelty. Although these data suggest that expression of inducible transcriptional
      factors are involved in fear, other non-shock ethologically based paradigms
      (predator or predator odor exposure) do not appear to increase c-fos in the
      lateral and basal nuclei. While the lack of c-fos expression may indicate that
      predator stress does not engage the lateral and basal amygdala nuclei, it may be
      that c-fos in the amygdala is not responsive to predator exposure. Therefore, egr
      1, which increases in the lateral nucleus following fear conditioning, footshock
      and novelty, was assessed to determine if its expression is induced in rats
      exposed to a cat. Five minutes of cat exposure did not increase expression of egr
      1 mRNA in the lateral nucleus of the amygdala. egr-1 was increased in the
      paraventricular nucleus of the hypothalamus, indicating cat-induced stress, and
      visual cortex compared to rats that were either confined for 5 min or handled. In
      the lateral periaqueductal gray, handled rats displayed a left hemisphere
      dominance, which disappeared in both the cat-exposed and confined group,
      suggesting that immobility, induced by either cat-induced stress or unstressed
      confinement, increased right hemisphere egr-1 expression. The results are
      discussed in a context of differences and similarities in neural circuitry for
      conditioned and unconditioned fear.

PMID- 15970223
TI  - Increased lateralization in rotational side preference in male mice rendered
      acallosal by prenatal gamma irradiation.
AB  - In order to test the hypothesis that the ontogenetic development of the corpus
      callosum is related to the establishment of behavioral laterality, the rotatory
      behavior in the free-swimming test was studied in male Swiss mice with callosal
      defects induced by exposure to gamma irradiations at the 16th embryonic day
      (total dose of 3 Gy). At adulthood, 43 irradiated and 56 non-irradiated mice were
      submitted to 3 sessions of the free-swimming rotatory test (diameter of the
      recipient=21 cm; session duration=5 min; inter-test interval=48 h). The number
      and direction of 30 degrees and 360 degrees turns were recorded. Animals were
      classified as side-consistent turners (to the right or to the left) when they did
      not change their preferred side of rotation in all three sessions and in both
      turning units. In general our results suggested that irradiated animals present
      more pronounced laterality than non-irradiated ones. In the irradiated group, the
      percentage of consistent turners was significantly higher than that of non
      consistent turners. In the first session, the percentage of animals that
      presented strong turning preferences in the acallosal group was higher than in
      the normal group. In first session, the acallosal group presented a higher
      average number of turns to preferred side than the normal group. Taken together,
      our results constitute an endorsement to the hypothesis that the normal
      development of the corpus callosum is related to the establishment of cerebral
      laterality.

PMID- 15970224
TI  - Long-term habituation of the startle response in mice evoked by acoustic and
      tactile stimuli.
AB  - The present study shows that repetitive presentation of tactile and acoustic
      stimuli evoke long-term habituation (LTH) of the startle response in C57BL/6J
      mice. This was indicated by a decrease in response strength over several days.
      For the LTH of the acoustic startle response two controls were included: first,
      developing hearing loss during the time of testing did not account for the
      startle decrease--only 7 days of acoustic stimulation but not 7 days of
      adaptation led to a decrease in the startle. Second, repetitive presentation of
      loud acoustic startle stimuli did not raise the auditory threshold, which might
      otherwise have accounted for the startle decrease: prepulse inhibition (used here
      as a hearing test) was identical after both 7 days of acoustic startle
      stimulation and 7 days without stimulation. This proves that LTH to tactile and
      acoustic stimuli is present and fully functional in mice.

PMID- 15970225
TI  - Effect of specific aspects of community social environment on the mortality of
      individuals diagnosed with serious illness.
AB  - The purpose of this study was to examine the prospective and contextual effects
      of urban community environment on mortality among Medicare beneficiaries who were
      67 years old or older in 1993, lived in the city of Chicago, and were
      hospitalized for one of 13 serious diseases. As expected, we found that
      advantageous socioeconomic context helps lower mortality risk among elderly
      patients over and above individual demographic and health background. We also
      found that collective efficacy was a health-enhancing social resource whereas
      criminal and violent activities in the community appeared to be deleterious.
      Inconsistent with our hypotheses, community social network density (measured by
      the size of social network and frequency of social interaction) was not
      protective but detrimental. Moreover, social support and the civic involvement of
      residents in the community do not seem to affect mortality. The complex
      relationship between community social environment and health found in this study
      may suggest that community-level social interventions based on social
      capital/social cohesion models are not likely to achieve fruitful results without
      concomitant effort in the economic and health care realm, at least in terms of
      influences on the health of older people once they are already ill.

PMID- 15970226
TI  - Neighborhood economic conditions, social processes, and self-rated health in low
      income neighborhoods in Texas: a multilevel latent variables model.
AB  - This paper develops and tests a comprehensive model to explain the relationships
      of neighborhood economic indicators to multiple dimensions of neighborhood social
      and physical organization as well as the pathways through which neighborhood
      social and physical characteristics influence individual health outcomes. We
      hypothesized that neighborhood poverty would be associated with lower collective
      efficacy, lower social capital, higher degrees of social and physical disorder,
      worse social processes pertaining to children such as trust, and higher degrees
      of fear of crime and racism. Neighborhood social and physical characteristics
      were hypothesized to mediate the effect of neighborhood poverty on self-rated
      health, both directly and indirectly through their influence on neighborhood
      differences in social support and health behaviors, which in turn affect
      individual health. The results, based on data from low-income neighborhoods in
      Texas, USA generally supported the model and indicated that the effect of
      neighborhood impoverishment on health is mediated by social and physical
      neighborhood characteristics.

PMID- 15970227
TI  - Social capital and substance use among Swedish adolescents--an explorative study.
AB  - Cross-sectional survey data on Swedish adolescents aged 12-18 was used to
      estimate the link between individual social capital and smoking, illicit drug use
      and binge drinking. Major conclusions drawn were (1) that social capital,
      indicated by measures of social participation and trust, was negatively
      correlated with the probability of smoking and illicit drug use, but (2) that
      social capital showed no statistically significant correlation with the
      probability of binge drinking.

PMID- 15970228
TI  - The pet connection: pets as a conduit for social capital?
AB  - There is growing interest across a range of disciplines in the relationship
      between pets and health, with a range of therapeutic, physiological,
      psychological and psychosocial benefits now documented. While much of the
      literature has focused on the individual benefits of pet ownership, this study
      considered the potential health benefits that might accrue to the broader
      community, as encapsulated in the construct of social capital. A random survey of
      339 adult residents from Perth, Western Australia were selected from three
      suburbs and interviewed by telephone. Pet ownership was found to be positively
      associated with some forms of social contact and interaction, and with
      perceptions of neighbourhood friendliness. After adjustment for demographic
      variables, pet owners scored higher on social capital and civic engagement
      scales. The results suggest that pet ownership provides potential opportunities
      for interactions between neighbours and that further research in this area is
      warranted. Social capital is another potential mechanism by which pets exert an
      influence on human health.

PMID- 15970229
TI  - Individual socio-economic status, community socio-economic status and stroke in
      New Zealand: a case control study.
AB  - There is considerable debate about the association between individual socio
      economic status, community socio-economic status and health. The current study
      examines individual data from a case-control study of stroke (n = 3489) conducted
      in Auckland, New Zealand. The study sought to identify whether individual socio
      economic status (as measured by income from lifetime occupation) and community
      socio-economic status (measured in a number of ways) predicts the onset of stroke
      both independently and after controlling for individual risk factors (e.g.,
      smoking, obesity and hypertension). Logistic regression results show that
      individual socio-economic status and all of the community socio-economic status
      measures predict the onset of stroke before controlling for individual risk
      factors. However, there is a high correlation between the various measures of
      community socio-economic status. Stepwise regression results suggest that average
      household income is the measure of community-level socio-economic status with the
      greatest predictive power. The results suggest that individual income and average
      household income are significant predictors of onset of stroke both independently
      and after controlling for behavioural and medical risk factors. Logistic
      regression analysis of the pathway suggests that individual income is a
      significant predictor of smoking and obesity, and that community socio-economic
      status is a significant predictor of heart disease, heavy drinking, diabetes,
      smoking and obesity.

PMID- 15970230
TI  - "This glorious twilight zone of uncertainty": mental health consultations in
      general practice in New Zealand.
AB  - General practitioners provide treatment for the majority of people diagnosed as
      having a mental disorder in New Zealand, but much research suggests that they
      fail to diagnose many common mental disorders. This paper explores the issue of
      GP recognition of mental health problems through four discussion groups with GPs
      from the lower half of the North Island of New Zealand. GPs were asked to
      consider what they thought their role was in relation to mental health, what
      facilitated discussion of mental health issues in consultations and what could
      influence patients to disclose mental health problems. The analysis of the data
      collected drew on thematic and discourse analysis. Four key domains that had an
      impact on the consultation were identified, which were categorised as practice
      pressures, socio-cultural factors, the medico-legal framework and the
      consultation process. GPs employ a number of strategies to respond to the
      systemic and social issues influencing the consultation. This research suggests
      that GPs do recognise mental health problems in patients, but that a number of
      important factors result in the consultations not being labeled as mental health
      ones. The paper concludes by offering a framework for the mental health
      consultation that illustrates the systemic issues that GPs consider when making
      decisions about mental health consultations.

PMID- 15970231
TI  - 'At the point at which you can do something about it, then it becomes more
      relevant': informed consent in the pharmacogenetic clinic.
AB  - Sociological investigation of informed consent has generated rich and complex
      descriptions of the clinical encounter, often challenging the straightforward
      picture painted by medical ethicists. This paper builds on this work, drawing on
      ideas from the Sociology of Science and Technology, to explore informed consent
      issues surrounding the use of the drug Herceptin, widely cited as an example of a
      novel approach to drug development called pharmacogenetics. Drawing on
      qualitative semi-structured interviews with 25 UK-based breast cancer
      specialists, this paper explores Herceptin's disputed epistemological status, as
      an example of pharmacogenetics or as something out of the ordinary in terms of
      clinical practice. It considers how, in turn, this impacts on the way in which
      informed consent is sought and influenced by clinicians' desire to protect
      patients from possibly distressing test results. It highlights the flexible,
      contingent and context dependent nature of informed consent in the clinical
      setting.

PMID- 15970232
TI  - Views of US researchers about informed consent in international collaborative
      research.
AB  - Informed consent poses challenges in all settings. Challenges may be particularly
      great in international collaborative research, where cultural perspectives may
      differ, and where education levels and language may be barriers to participant
      understanding. We conducted a written survey and focus groups with US health
      researchers doing research in developing countries, asking about informed consent
      and other ethical issues in their research. We present here both qualitative and
      quantitative data relevant to informed consent. Qualitative data revealed that
      researchers' experiences and beliefs about informed consent fell into three
      paradigms: regulatory, community, and individual. The regulatory paradigm refers
      to researchers' views and practices relating to informed consent requirements of
      institutional review boards and other oversight bodies. The community paradigm
      refers to researchers' approach to the content and methodology of informed
      consent in the context of long-term relationships between research teams and
      study communities. Researchers emphasized the importance of these relationships
      for creating and maintaining communication fundamental to the informed consent
      process. Finally, the individual paradigm refers to researchers' views about
      individual participants' understanding and decision-making process regarding
      research. Researchers described community-level influences on participants'
      decision-making, but stressed the need for individual comprehension and voluntary
      participation. While these paradigms are distinct, they also are intertwined.
      Quantitative data supported the existence of these three paradigms in
      respondents' characterization of informed consent. Researchers frequently stated
      that legal language on the consent forms was meaningless (52%). Forty-four
      percent of researchers had consulted with community leaders, and 23% believed the
      consent process focuses too much on the individual, rather than on family or
      community. Most researchers (82%) reported that the consent process was an
      important means of educating participants about the study. Fifty-four percent of
      researchers believed participants did not understand placebos. Further research
      is needed to understand how culture and relationships affect research
      participation, and to provide information and dialogue among researchers,
      oversight bodies and community representatives about appropriate ways to approach
      informed consent in international research.

PMID- 15970233
TI  - The effect of immigrant generation on smoking.
AB  - Immigrants to the US are not only an increasingly significant demographic group
      but overall they also have lower socioeconomic status (SES) than the native-born.
      It is known that tobacco use is a major health risk for groups that have low SES.
      However, there is some evidence that tobacco use among certain immigrant groups
      is lower than among the respective native-born ethnic group, and that immigrant
      assimilation is positively related to tobacco use. We investigated the
      relationship between immigrant generation and daily smoking, using the Tobacco
      Use Supplement of the Current Population Survey (TUS-CPS), 1995-96, a national
      data set representative of the US general and immigrant populations. Our
      multivariate logistic regression analysis of the relationship between immigrant
      generation and daily smoker status (n = 221,798) showed that after controlling
      for age, gender, race/ethnicity, SES variables (i.e. equivalized household
      income, education, occupation), and central-city residence, the odds of being a
      daily smoker were highest among US-born individuals of US-born parents (reference
      group) and lowest among foreign-born individuals (95% CI: 0.54-0.62). Being a
      second-generation immigrant (i.e. US born) with two immigrant parents also
      conferred a protective effective from smoking (95% CI: 0.64-0.77). However,
      having only one foreign-born parent was not protective against smoking. Testing
      for interaction effects, we also found that being foreign born and being second
      generation with two immigrant parents were especially protective against smoking
      among females (vis-a-vis males); racial/ethnic minorities (vis-a-vis whites); and
      low-income individuals (vis-a-vis high-income individuals). We discuss possible
      mechanisms that may explain the protective effect against smoking of being
      foreign born and being second generation with two immigrant parents, including
      differences in the stage of the tobacco epidemic between immigrants' countries of
      origin and the US, the "healthy immigrant effect", and anti-smoking socialization
      in immigrant families.

PMID- 15970235
TI  - Self-reported health as a cultural health determinant in Arab and Jewish Israelis
      MABAT--National Health and Nutrition Survey 1999-2001.
AB  - Subjective health (SH) status serves as a measure of health in many studies of
      health-related issues as it is a good predictor of mortality, morbidity, and use
      of health services. The measure is used in many population groups. However, the
      degree to which it measures the same condition in different ethnic groups is not
      clear. Within Israel's first National Health and Nutrition Survey (MABAT)
      conducted during 1999-2001, face-to-face interviews were held with 3222 Israeli
      interviewees, 2379 Jews and 843 Arabs, aged between 25-64 years. Respondents
      reported their SH, co-morbidity, and other socioeconomic characteristics. Arabs
      reported higher levels of SH than Jews. In logistic regression analysis, co
      morbidity was a much stronger correlate of poorer SH in the Arab than in the
      Jewish population. The association between socioeconomic variables depended on
      ethnic group and sex. The findings indicate that SH in Jews and Arabs does not
      necessarily have the same meaning in relation to objective measures of health,
      and caution should be exercised in the use of this measure in different
      population groups with different cultures. Arabs tend to evaluate health better
      than Jews even though life expectancy is lower and morbidity and mortality are
      higher in the former population group. Yet diagnosis of a disease increases the
      frequency of reporting lower SH, more in Arabs than in Jews.

PMID- 15970234
TI  - Do healthy behaviors decline with greater acculturation? Implications for the
      Latino mortality paradox.
AB  - Relative to non-Latino whites, Latinos in the United States have a lower
      socioeconomic status (SES) profile, but a lower all-cause mortality rate. Because
      lower SES is associated with poorer overall health, a great deal of controversy
      surrounds the Latino mortality paradox. We employed a secondary data analysis of
      the 1991 National Health Interview Survey to test the health behavior and
      acculturation hypotheses, which have been proposed to explain this paradox. These
      hypotheses posit that: (1) Latinos have more favorable health behaviors and risk
      factor profiles than non-Latino whites, and (2) Health behaviors and risk factors
      become more unfavorable with greater acculturation. Specific health behaviors and
      risk factors studied were: smoking, alcohol use, leisure-time exercise activity,
      and body mass index (BMI). Consistent with the health behaviors hypothesis,
      Latinos relative to non-Latino whites were less likely to smoke and drink
      alcohol, controlling for sociodemographic factors. Latinos, however, were less
      likely to engage in any exercise activity, and were more likely to have a high
      BMI compared with non-Latino whites, after controlling for age and SES. Results
      provided partial support for the acculturation hypothesis. After adjusting for
      age and SES, higher acculturation was associated with three unhealthy behaviors
      (a greater likelihood of high alcohol intake, current smoking, a high BMI), but
      improvement in a fourth (greater likelihood of recent exercise). Gender-specific
      analyses indicated that the observed differences between Latinos and non-Latino
      whites, as well as the effects of acculturation on health behaviors, varied
      across men and women. Results suggest that the health behaviors and acculturation
      hypotheses may help to at least partially explain the Latino mortality paradox.
      The mechanisms accounting for the relationship between acculturation and risky
      behaviors have yet to be identified.

PMID- 15970236
TI  - Combat stress reactions, posttraumatic stress disorder, cumulative life stress,
      and physical health among Israeli veterans twenty years after exposure to combat.
AB  - This study examined the association of initial combat stress reaction (CSR),
      chronic post-traumatic stress disorder (PTSD) and cumulative life stress on
      physical health 20 years after the 1982 war with Lebanon, in a sample of 504
      Israeli veterans of the war. Two groups were assessed: male veterans who fought
      and suffered from CSR and a matched group of male veterans from the same units
      who did not exhibit such reactions. Twenty years following the war, participants
      were asked to rate their general physical health status, report health complaints
      and risk behaviors, and were screened for PTSD. CSR and, to a greater extent,
      PTSD, were found to be associated with general self-rated health, chronic
      diseases and physical symptoms, and greater engagement in risk behaviors. CSR and
      PTSD were also related to greater cumulative life stress since the war. Both
      negative and positive life events were independently related to most of the
      physical health measures but did not account for the associations of CSR and PTSD
      with poorer health. Tests of the interactions between CSR, PTSD and life stress
      in their association with physical health and risk behaviors showed that PTSD
      suppressed the effects of additional life stress (negative life events had a
      weaker effect on health among participants with PTSD).

PMID- 15970237
TI  - Sexuality after breast cancer treatment: changes and coping strategies among
      Japanese survivors.
AB  - Sexuality after a cancer diagnosis has long been neglected in the clinical and
      research settings in many countries. In particular, research in Asia on sexuality
      and cancer among women is extremely scarce. Semi-structured interviews were
      conducted with 21 Japanese women with breast cancer (mean age 42.2 years; median
      length between surgery and first interview 17 months) to explore their views on
      sexuality following breast cancer treatment. Analysis using the Grounded Theory
      approach revealed four major themes: (a) hesitation in resuming sex after
      treatment, (b) sexual changes after resuming sex, (c) coping attitudes to the
      changes, and (d) long-term outcomes of the relationship with partners. Contrary
      to Japanese breast surgeons' optimistic outlooks, the majority of informants
      referred to the impact of treatment on the physical as well as psychological
      aspects of their sexuality. Factors that influenced women's experiences included
      the pace of their psychological and physical recovery after treatment, fear of
      their partner's negative response, the importance of the sexual relationship for
      the couple, and their partner's understanding and support. Suggestions for
      medical professionals on how to support women's sexuality after cancer are
      discussed with reference to the Japanese socio-cultural and medical context.

PMID- 15970238
TI  - Decision-makers and the usefulness of research evidence in policy implementation-
      a case study from Lao PDR.
AB  - The involvement of researchers in the policy process and policy-makers in
      research is little studied, particularly in developing countries. In 1993, the
      Lao National Drug Policy (NDP) was endorsed in a consultative process involving
      many stakeholders. Lao People's Democratic Republic is a poor country in South
      East Asia. Five pilot provinces were selected for implementation of the policy,
      which had a health system research (HSR) component. This case study explores
      decision-makers' knowledge and attitudes regarding the usefulness of HSR in the
      NDP implementation process. Ninety decision-makers from different health
      institutions including hospitals, medical schools and main drug suppliers were
      surveyed using a self-administrated structured questionnaire, filled in during a
      NDP conference in 2001. Results from six HSR projects related to the NDP
      implementation had been presented during the conference, but also 6 months
      previously and through written reports. There were 75 respondents (83% of
      attendees, 90% of whom were men), 39% with medical, 50% with pharmacy and 11%
      with other background. Ninety-eight percent of the participants found operational
      research useful, and 87% supported it to be an element of the NDP. Two-thirds
      knew the objectives of the NDP. There was no significant difference in knowledge
      and attitudes between pilot and non-pilot provinces and between professions.
      Ninety-two percent were aware of the Essential Drug List, and 88% found it
      adequate to drug need. Ninety-seven percent agreed with generic drug prescribing.
      Seventy percent reported to have heard about Good Pharmacy Practice (GPP), but
      only a few could explain it. Although most participants agreed that HSR should be
      one main component of the NDP and found HSR results useful, few had heard about
      them before the conference, and research was not well understood. The paper
      discusses various factors influencing decision-makers' perceptions of usefulness
      of research in this case during the NDP implementation process. It is concluded
      that the acceptance of research and major NDP concepts probably is a result of
      close interaction between researchers and policy-makers and that the interface
      between research and policy-making needs further studies.

PMID- 15970239
TI  - Resemblance talk: a challenge for parents whose children were conceived with
      donor gametes in the US.
AB  - The normative folk model of kinship in the US continues to attach great
      significance to "blood" relationships. These implicit genetic links are commonly
      reinforced through observations about a child's physical similarity to parents or
      other family members, i.e., "resemblance talk". This paper explores the meanings
      of resemblance and resemblance talk for parents drawing on semi-structured
      interviews with 148 heterosexual couples who had used a donor gamete to conceive
      at least one living child. For parents of children conceived with donor eggs or
      sperm, resemblance talk represents the ongoing threat that comments about
      physical appearance could stigmatize their children or cast doubt on the
      legitimacy of their family structure. Furthermore, these concerns were present
      regardless of whether a sperm or egg donor had been used and irrespective of the
      parents' disclosure decision, i.e., whether or not their children were told of
      the true nature of their conception. Parents found that resemblance talk was not
      only ubiquitous, unavoidable, and uncontrollable, but it also had the capacity to
      exacerbate ongoing uncertainties about their disclosure decision (or lack of
      one), worries about establishing their child within the extended family, and
      apprehension that insensitive remarks could make the child feel different from
      other family members. As a result, many couples spent considerable energy
      developing a variety of strategies for managing resemblance talk that included
      genetic plausibility arguments, "passing", and strategic silence. We conclude
      that parents of children conceived with a donor address and contest normative
      definitions of kinship and family, including stigma and otherness, resist
      challenges to the family they have created, and, to some extent, rework their
      allegiance to cultural norms to suit their own needs. Because resemblance talk
      and disclosure decisions are frequently tied to each other, it is likely that if
      the public were more accepting of difference, parents would likely feel more
      comfortable with disclosure. Yet resemblance talk may make it more difficult for
      parents to disclose, not easier, as long as attitudes about the implicit primacy
      of genetic connectedness prevail.

PMID- 15970240
TI  - The work of forgetting: germs, aborigines and postcolonial expertise in the
      Northern Territory of Australia.
AB  - Based on anthropological field research (1997-2000) within the Department of
      Health and Community Services in the Northern Territory in Australia, this paper
      explores the lingering features of colonial logic in the pastoral work of public
      health workers in the Northern Territory of Australia. The public health
      professionals drawn to work in this space are determined to remedy what is wrong
      with culturally acceptable solutions. But viewed from an anthropological
      perspective, the way in which health professionals conceptualise the problems
      they need to solve ultimately serves to reinforce the reality of the need for
      their continued tutelary presence. This paper aims to draw out the complex ways
      in which this interventionary effect is secured, concentrating in particular on
      the role played by progressive ideologies of participatory development and
      information sharing. It argues that through a complex process of forgetting, the
      otherwise innocuous gestures of public health goodwill recreate a mandate for
      more public health intervention. This is not a simple moral tale where analysts
      can easily identify good and bad practices and thus distance themselves from the
      difficulties involved. Rather, by emphasising the honest commitments to
      improvement in situations of mass illness and preventable disease that health
      professionals bring to their work, and the burden they bear in being conscious of
      the recent colonial past, the paper aims to avoid the judgement that this sort of
      work is easy to get right.

PMID- 15970241
TI  - Failure to seek needed medical care: results from a national health survey of
      Icelanders.
AB  - The study focuses on access to outpatient medical care in Iceland--a socialized
      health care system. As in other systems of this sort, equal access to needed
      services (equity) is a fundamental principle. Despite governmental claims that
      access to health services is "easy" and "roughly equal", the study indicates
      substantial and rather extensive variations in equity of care. More specifically,
      younger individuals, the non-widowed, the economically troubled, individuals with
      inflexible daily schedules, the chronically ill, those who had incurred high out
      of-pocket costs relative to their family income, and those who didn't have a
      physician care discount card, were more likely than others to postpone or cancel
      an MD visit they thought they needed. Furthermore, younger age, economic
      troubles, chronic medical conditions, no family physician, and no physician care
      discount card, were all related to under-utilization, based on medical specialist
      criteria of recommended medical care for symptoms. Although the results show that
      access problems originate in part outside the health care system, they also
      suggest revision of current health policy, in order to adequately address
      existent inequities in service delivery.

PMID- 15970242
TI  - Utility-driven evidence for healthy cities: problems with evidence generation and
      application.
AB  - The question whether the WHO Healthy Cities project 'works' has been asked ever
      since a number of novel ideas and actions related to community health, health
      promotion and healthy public policy in the mid 1980s came together in the Healthy
      Cities Movement initiated by the World Health Organization. The question,
      however, has become more urgent since we have entered an era in which the drive
      for 'evidence' seems all-pervasive. The article explores the nature of evidence,
      review available evidence on Healthy Cities accomplishments, and discusses
      whether enough evidence has been accumulated on different performances within the
      realm of Healthy Cities. A main point of reference is the European Healthy Cities
      Project (E-HCP). Building on the information gathered through documentary
      research on the topic, it is concluded that there is fair evidence that Healthy
      Cities works. However, the future holds great challenges for further development
      and evidence-oriented evaluations of Healthy Cities. There are problems with (1)
      the communication of evidence, (2) the tension between the original intention of
      the Healthy Cities Movement and its current operations, and (3) the complex
      nature of Healthy Cities and the methodological tools currently available.

PMID- 15970243
TI  - Understanding the relationship of maternal health behavior change and
      intervention strategies in a Nicaraguan NGO network.
AB  - Few studies of community interventions examine independent effects of investments
      in: (1) capital (i.e., physical, human and social capital), and (2) management
      systems (e.g., monitoring and evaluation systems (M&E)) on maternal and child
      health behavior change. This paper does this in the context of an inter
      organizational network. In Nicaragua, international non-governmental
      organizations (NGOs) and local NGOs formed the NicaSalud Federation. Using Lot
      Quality Assurance Sampling (LQAS), 14 member organizations took baselines
      measures of maternal safe motherhood and child health behavior indicators during
      November 1999 and August 2000, respectively, and final evaluation measures in
      December 2001. In April 2002, retrospective interviews were conducted with
      supervisors and managers in the 14 organizations to explore changes made to
      community health strategies, factors associated with the changes, and impacts
      they attributed to participating in NicaSalud. Physical capital (density of
      health huts), human capital (density and variety of paramedical personnel) and
      social capital (density of health committees) were associated with pregnant women
      attending antenatal care (ANC) 3+ times, and/or retaining ANC cards. The variety
      of paramedic personnel was also associated with women making post-partum visits
      to clinics. Physical capital (density of health huts) and social capital (density
      of health committees and mothers' clubs) were associated with child diarrhea case
      management indicators. One safe motherhood indicator (delivery of babies by a
      clinician) was not associated with intervention strategies. At the management
      level, NicaSalud's training of members to use LQAS for M&E was associated with
      the number of strategic and tactical changes they subsequently made to
      interventions (organizational learning). Organizational learning was related to
      changes in maternal and child health behaviors of the women (including changes in
      the proportion using post-partum care). As the latter result would not have
      occurred without NicaSalud, we conclude that this inter-organizational network
      provided added value by instigating organizational learning.

PMID- 15970244
TI  - The moral career of poor patients in free clinics.
AB  - This paper explores the lived experiences and the identity processes attached to
      attendance at free clinics. It draws on a qualitative study of 94 patients and 37
      professionals who were interviewed at four free clinics in France. Since these
      facilities are for the poor and for people without health coverage, attendance
      reflects a medical experience as well as an experience of assistance, both of
      which have an impact on healthcare utilisation. Nevertheless, the meaning
      attached to the recourse to free clinics and the patients' lived experiences
      change over time and depend on interactions with clinic staff. This study
      proposes a typology of care recourse modes (occasional, regular and inconsistent
      attendance) crossed with different types of lived experiences. Occasional
      attendance and distant patient-professionals relationships, often due to the
      humiliation that some people feel when they have to ask for social assistance,
      characterise the first time people have recourse to care. Patients commit to
      regular follow-ups only when they have come to terms with their position in the
      medical and assistance system, doing so by rationalising and adjusting their
      identity. Our aim in discussing our findings is to gain greater insight into the
      utilisation of healthcare by different population groups and in different
      contexts.

PMID- 15970246
TI  - Hair thread tourniquet syndrome in adolescents: a presentation and review of the
      literature.
AB  - Hair thread tourniquet syndrome has been recognized since the 1600s when a
      strangulating hair was reported around the glans penis. Since that time sporadic
      reports have appeared in the literature describing strangulation of appendages by
      human hair. Most often the constriction involves fingers, toes, or the penis.
      There are several reports of clitoral strangulation. Most cases present to their
      primary care provider or emergency department. A high index of suspicion is
      required for diagnosis in order to prevent prolonged devascularization. We
      describe a hair thread tourniquet syndrome of the labia minora in a 13-year-old.
      It was successfully treated with exam under anesthesia and resection of the
      devascularized tissue. We believe this is the oldest patient described as well as
      the only description of hair tourniquet syndrome of the labia minora. Prompt
      recognition of this unusual condition is essential for treatment of this
      potentially serious problem.

PMID- 15970247
TI  - Menstrual and contraceptive issues among young women with developmental delay: a
      retrospective review of cases at the Hospital for Sick Children, Toronto.
AB  - OBJECTIVES: To define the clinical characteristics of, and management options
      offered to, young women with developmental delay referred to The Hospital for
      Sick Children gynecology clinic in Toronto for menstrual suppression and
      contraception. To review the primary caregiver concerns and preferences with
      regards to menstruation and contraception. METHODS: A retrospective chart review
      of hospital records of young women with developmental delay referred to the
      gynecology clinic at The Hospital for Sick Children, Toronto from 1998 to 2003.
      RESULTS: A total of 72 charts were reviewed from clinic visits between 1998 to
      2003. Ages range from 8 to 17 years with an unknown cause of their cognitive
      disability in 44% and medium to high support needs in the majority. Forty-three
      percent were still premenarcheal when first brought to the gynecology clinic by
      their families or caregivers. The main reason for consult was menstrual-related
      in 90%, with concerns related to hygiene and problems coping. CONCLUSIONS:
      Caregivers often approach physicians for menstrual suppression prior to menarche
      with a primary concern of personal hygiene. Medical suppression of menstruation
      can be successfully achieved. Depo-Provera was the most commonly prescribed and
      accepted method of menstrual suppression within our population.

PMID- 15970248
TI  - Body mass index extremes in a British adolescent gynecology clinic.
AB  - STUDY OBJECTIVE: To identify the prevalence of patients with BMI extremes
      (BMI>88% or < 2%) in our Adolescent Gynecology clinic and audit their weight
      management. DESIGN: Retrospective case series. SETTING: The Adolescent Gynecology
      Clinic of a British District General Hospital PARTICIPANTS: All patients aged 12
      17 years when first seen in the Adolescent Gynecology clinic from 1997 to 2003.
      INTERVENTIONS: Retrospective data collection on biometry and weight management
      interventions. MAIN OUTCOME MEASURES: The percentage of obese (BMI>98(th)
      percentile for age), overweight (BMI 88(th)-98(th) percentile) and underweight
      (BMI < 2(nd) percentile) based on published percentile BMI curves for the UK
      adolescent population, the proportion of patients with extreme BMI that were
      offered intervention, the types of intervention offered, the proportion of
      patients whose BMI improved after the intervention, and the number of patients
      with BMI>88% among smokers were compared to non-smokers. RESULTS: Of the 125
      patients 24% were obese, an additional 17% overweight and 1% underweight. The
      expected figures in the general population are 2%, 10% and 2% respectively (P <
      0.001; test of a single proportion). Weight management intervention was offered
      to 47% of patients with extreme BMI. The BMI improved in 36% of the patients who
      were offered and 14% of patients who were not offered intervention (P=0.066;
      chi(2)). There was no statistically significant difference between smokers and
      non-smokers in the proportion of patients with BMI>88% (P=0.93; chi(2)).
      CONCLUSION: There is significantly increased prevalence of obese and overweight
      women among adolescent gynecological patients. The need for management of the BMI
      of these patients has not been always been recognized and treatment is not
      particularly effective. The results indicate a need for defined strategies and
      additional resources for obesity management.

PMID- 15970249
TI  - Youth preferences for prenatal and parenting teen services.
AB  - STUDY OBJECTIVE: Parenting teens served by a teen-tot program and teens from a
      prenatal clinic participated in focus groups to explore their perceptions of
      medical care, social services, and psycho-educational parenting groups. DESIGN:
      The teens met in four focus groups, two prenatal and two postnatal. SETTING:
      Teens receiving care from a teen-tot program and associated prenatal clinic in a
      large metropolitan area in New England. PARTICIPANTS: A total of 16 pregnant
      (n=6) and parenting (n=10) teens ages ranging from 16 to 21 years (13 African
      American, 2 Latina, and 1 Haitian) participated in the four focus groups.
      METHODS: A qualitative focus group study was performed. Structured, culturally
      sensitive questions guided the discussion based on a hypothetical case scenario.
      Themes were identified through grounded theory with three coders and differences
      were reconciled. RESULTS: The groups revealed prenatal and postnatal mothers
      valued medical and social services provided in a teen-focused hospital clinic.
      Prenatal teens looked to providers for health education services and group
      support. Parenting teens requested consistent doctors for their children and
      social supports for themselves. Both groups desired assistance with social
      services, education, housing, and finances as well as educational services for
      fathers. CONCLUSIONS: Teen parents' perceptions and suggestions for services are
      critical to program development that meets the needs of participants.

PMID- 15970250
TI  - Post-traumatic vulvar hematoma secondary to coagulopathy caused by rickettsial
      infection.

PMID- 15970251
TI  - What's your diagnosis? Inflamed vulvar papules in a 7-year-old girl.

PMID- 15970252
TI  - Depot medroxyprogesterone acetate (DMPA, Depo-Provera) in adolescents: what is
      next after the FDA black box warning.

PMID- 15970253
TI  - In favor of continued use of depot medroxyprogesterone acetate (DMPA, Depo
      Provera) in adolescents.

PMID- 15970254
TI  - No bones about it--depot medroxyprogesterone acetate remains an excellent
      contraceptive option for adolescents.

PMID- 15970255
TI  - Management quandary: secondary amenorrhea and disordered eating.

PMID- 15970256
TI  - Approach to the adolescent girl as she transits from irregular to regular
      menstrual cycles.

PMID- 15970257
TI  - Teens and IUDs.

PMID- 15970258
TI  - Phage therapy: an attractive option for dealing with antibiotic-resistant
      bacterial infections.

PMID- 15970259
TI  - Novel second messenger offers drug development opportunities.

PMID- 15970260
TI  - Flu pills for a pandemic threat.

PMID- 15970261
TI  - Genes predict childhood leukemia outcome.

PMID- 15970262
TI  - Peter Hug on the Roche philosophy to partnering. Interview by Stephen Carney.

PMID- 15970263
TI  - British Columbia's biotechnology industry: blending research, business and
      lifestyle.

PMID- 15970264
TI  - Widening bottlenecks in drug discovery: glimpses from Drug Discovery Technology
      Europe 2005.

PMID- 15970265
TI  - Imaging mass spectrometry: fundamentals and applications to drug discovery.
AB  - Imaging mass spectrometry (IMS) encompasses a variety of techniques that enable
      the chemical imaging of analytes, which range in size from atoms and small
      molecules to intact proteins, directly from biological tissues. IMS is
      transforming specific areas in biological research with its unique combination of
      chemical and spatial information. Innovations in instrumentation and imaging
      protocols will make this approach invaluable at many stages of the drug discovery
      process, including pharmacological target screening and evaluating the
      distribution of drug and drug metabolites in cells and tissues. The fundamentals
      and unique methodology of IMS are discussed, along with exciting new applications
      to drug discovery science.

PMID- 15970266
TI  - Kinomics: characterizing the therapeutically validated kinase space.
AB  - The annotation and visualization of medicinally relevant kinase space revealed
      that kinase inhibitors in the clinic are, on average, of higher molecular weight
      and more lipophilic than all other clinically investigated drugs. Tyrosine
      kinases from the vascular endothelial growth factor and epidermal growth factor
      receptor families are the most pursued targets. Furthermore, oncological
      indications account for 75% of all kinase-related clinical interest. In addition,
      analysis of the similarity between kinase targets with respect to sequence,
      selectivity and structure has revealed that kinases with > or =60% sequence
      identity are most likely to be inhibited by the same classes of compounds and
      have similar ATP-binding sites. The identification of this threshold, together
      with the widely accepted representation of the sequence-based kinase space, is
      expanding our understanding of the clinical and structural space of the kinome.

PMID- 15970267
TI  - Not all viruses are bad guys: the case for reovirus in cancer therapy.
AB  - Efforts to improve on cancer therapy have begun to capitalize on recent advances
      in our understanding of tumorigenesis. Tumor-specific characteristics are being
      exploited to develop selective antibodies and pharmacological inhibitors that
      specifically target cancer cells, and these agents are already showing clinical
      promise. None of these approaches, however, has captured our imagination as much
      as the use of replication-competent viruses to kill cancer cells. Whereas normal
      cells resist replication, tumor cells have an impaired antiviral response that
      sensitizes them to oncolytic viruses. One such virus is reovirus, a benign,
      naturally occurring virus that can effect tumor regression in animal models.
      Reovirus is demonstrating much promise in pre-clinical studies of cancer therapy
      and in clinical trials, where a lack of toxicity and signs of efficacy are
      generating excitement for this novel potential cancer therapeutic.

PMID- 15970268
TI  - The transcriptome's drugable frequenters.
AB  - Microarray studies are widely employed in the exploratory phase of the drug
      discovery process. Expectations raised by the genomics revolution led to the
      belief that they would rapidly lead to the identification of novel drug targets.
      However, a few basic questions were often overlooked. Are members of drugable
      gene families properly represented in the transcriptome? Or are they poorly
      expressed and below the detection limit of the microarray technology? This review
      explores the representation of drug targets and components of downstream cellular
      signaling pathways in the transcriptome. It appears that members of drugable gene
      families are underrepresented in the transcriptomes of non-pathological human
      tissues. But, they are represented at or above the expected frequency in the
      differential transcriptome (i.e. the set of genes that changes expression upon a
      change in cellular environment). Analysis of differential gene expression on a
      genome-wide scale will therefore give a comprehensive overview of cellular
      pathways and possible drug targets.

PMID- 15970269
TI  - Web services in the life sciences.
AB  - Web services provide a standard way of publishing applications and data sources
      over the internet, enabling mass dissemination of knowledge. In the life
      sciences, the web-service approach is seen as being a road to standardizing the
      multitude of tools available from different providers. In this article, we
      present an overview of the technology (focusing on life-science applications), we
      list the currently available service providers and we discuss advanced issues
      raised by the concept.

PMID- 15970273
TI  - Rotting softly and stealthily.
AB  - The soft rot erwiniae, which are plant pathogens on potato and other crops world
      wide, synthesize and secrete large quantities of plant cell wall degrading
      enzymes that are responsible for the soft rot phenotype, earning them the epithet
      'brute force' pathogens. They have been distinguished from classic 'stealth'
      pathogens, such as Pseudomonas syringae, which possesses an extensive battery of
      Type III secreted effector proteins and phytotoxins to manipulate and suppress
      host defences. However, recent studies, including whole-genome sequencing, are
      revealing many components of stealth pathogenesis within the soft rot erwiniae
      (SRE), suggesting that 'stealth' and 'brute force' should not be regarded as
      mutually exclusive modes of pathogenesis.

PMID- 15970274
TI  - Child passenger safety and the immunity fallacy: Why what we are doing is not
      working.
AB  - Motivating parents to take certain safety precautions when traveling with their
      children remains an elusive challenge for advocates, as caregiver naivete
      contributes to poor parental participation in safety-seat checks, low booster
      seat use, poor adherence to rear-seat positioning, and intermittent safety-belt
      use. Because of inherent human biases and unfortunate characteristics of vehicle
      travel, it is argued that most caregivers possess an immunity fallacy, or a
      reduced perception of risk for motor vehicle injury to their children.
      Consequently, traditionally designed child passenger safety campaigns, which are
      primarily informational, fail to have an impact on most parents. Rather, for
      maximum behavioral success, injury prevention messages must shock and surprise
      parents into paying attention to something they would normally dismiss as
      unimportant.

PMID- 15970275
TI  - A possible role for the canonical Wnt pathway in endocrine cell development in
      chicks.
AB  - Wnt signalling is involved in many developmental processes such as proliferation,
      differentiation, cell fate decisions, and morphogenesis. However, little is known
      about Wnt signalling during pancreas development. Multiple Wnt ligands and
      Frizzled receptors are expressed in the embryonic mouse pancreas, the surrounding
      mesenchyme, and have also been detected in the chicken endoderm during
      development. The aim of this study was to investigate the role of canonical Wnt
      signalling on endocrine cell development by use of the in ovo electroporation of
      the chicken endoderm. Overexpression with a constitutive active form of beta
      catenin in combination with Ngn3 resulted in reduced numbers of glucagon cells.
      dnLEF-1 or naked-1 did not alter endocrine cell differentiation when co-expressed
      with Ngn3, but dnLEF-1 appeared to have some potential for inhibiting
      delamination of Ngn3 cells. In addition, neuronal beta-III-tubulin, which had
      previously been considered a specific marker for neuronal cells, was observed in
      the pancreas and was upregulated in the electroporated Ngn3 cells and thus may be
      a new endocrine marker in the chicken.

PMID- 15970276
TI  - A novel EID family member, EID-3, inhibits differentiation and forms a homodimer
      or heterodimer with EID-2.
AB  - The EID family members, i.e., E1A-like inhibitor of differentiation-1 (EID-1) and
      EID-1-like inhibitor of differentiation-2 (EID-2), were identified as negative
      regulators of cellular differentiation. EID-1 seems to inhibit differentiation by
      blocking histone acetyltransferase activity and EID-2 possibly inhibits
      differentiation through binding to class I histone deacetylases (HDACs). Here, we
      report a novel inhibitor of differentiation exhibiting homology with EID-2 termed
      EID-3 (EID-2-like inhibitor of differentiation-3). Like EID-2, EID-3 inhibited
      MyoD- and GRalpha-dependent transcription and blocked muscle differentiation in
      cultured cells by binding to class I HDACs. Unlike that of EID-2, the C-terminus,
      but not the N-terminus, of EID-3 was required for nuclear localization. EID-3
      formed a homodimer or heterodimer with EID-2. These results suggest that EID-3
      inhibits differentiation by blocking transcription as a complex in cells.

PMID- 15970277
TI  - Induction of apoptosis in the lung tissue from rats exposed to cigarette smoke
      involves p38/JNK MAPK pathway.
AB  - Smoking is a major cause of human lung cancer. Past studies suggest that
      apoptosis might influence the malignant phenotype, but little is known about the
      association between apoptosis and cigarette smoke (CS)-induced lung pathogenesis.
      Using an in situ cell death detection kit (TA300), the association of CS with
      apoptosis was determined in a concentration-dependent manner. Furthermore, the
      expression of related proteins were investigated in the terminal bronchiole areas
      of the lung tissue from rats exposed to CS. Results showed that the expression of
      phosphotyrosine proteins was increased significantly in lung tissue of rats
      exposed to CS from 5 to 15 cigarettes. Using Western blotting and
      immunoprecipitation assay, Fas, a death receptor, was proved just be one of these
      phosphotyrosine proteins. CS triggered activation of MAP kinase (p38/JNK or ERK2)
      pathway, which led to Jun or p53 phosphorylation and FasL induction links Fas
      phosphorylation. Further, smoke treatment produced an increase in the level of
      proapoptotic proteins (Bax, t-Bid, cytochrome c and caspase-3), but a decline in
      Bcl-2, procaspase-8 and procaspase-9 proteins. Thus, CS-induced apoptosis may
      result from two main mechanisms, one is the activation of p38/JNK-Jun-FasL
      signaling, and the other is stimulated by the stabilization of p53, increase in
      the ratio of Bax/Bcl-2, release of cytochrome c; thus, leading to activation of
      caspase cascade.

PMID- 15970278
TI  - The effect of age on the enzyme activities of tryptophan metabolism along the
      kynurenine pathway in rats.
AB  - BACKGROUND: Quinolinic acid and other kynurenine metabolites of the oxidative
      metabolism of tryptophan play an important role in several pathophysiological
      conditions. We aimed to study the effect of age on the enzyme activities of
      tryptophan metabolism along the kynurenine pathway. METHODS: Enzyme activity was
      investigated in liver, kidneys and small intestine obtained from Sprague-Dawley
      rats of various ages (1 week, 2-3, 12 and 18 months). RESULTS: We found age
      related differences in the liver tryptophan 2,3-dioxygenase, small intestine
      indole 2,3-dioxygenase, liver and kidney kynurenine 3-monooxygenase activities,
      which decreased significantly with age. Also liver kynureninase activity declined
      with age, while the activity in kidneys did not show an evident age-related
      pattern from 2-3 months to 18 months of age. Liver kynurenine oxoglutarate
      transaminase was quite similar through all considered age groups, while the
      activity in kidneys was significantly lower in newborn rats and progressively
      increased up to 12 months, then significantly decreased at 18 months of age.
      Liver and kidney 3-hydroxyanthranilate 3,4-dioxygenase progressively and
      significantly increased from newborns to 12 months of age; in the group of rats
      aged 18 months, the enzyme activity tended to diminish, although not
      significantly. The liver aminocarboxymuconate-semialdehyde decarboxylase activity
      increased up to 12 months of age, then tended to decrease at 18 months, while in
      the kidneys, in which the activity was higher than in the liver at all the
      considered ages, the activity remained constantly elevated from 2-3 months to 18
      months of age. CONCLUSIONS: A progressive decline in the enzyme activities
      involved in tryptophan metabolism along the kynurenine pathway in rat tissues was
      found with age, except for aminocarboxymuconate-semialdehyde decarboxylase,
      which, on the contrary, was increased after 2-3 months to the other older groups
      of age. The altered metabolism of tryptophan with ageing can lead to a decreased
      biosynthesis of nicotinic acid, tryptophan being the major source of body stores
      of NAD coenzymes, which are involved in almost all biogenetic and biosynthetic
      pathways of the organism.

PMID- 15970279
TI  - Ovariectomy induces oxidative stress and impairs bone antioxidant system in adult
      rats.
AB  - BACKGROUND: There is increasing evidence suggesting the role of free radicals in
      bone resorption and bone loss. Ovariectomized rats have been used as the animal
      model for the study of osteoporosis. Oxidative stress due to reactive oxygen
      species (ROS) can cause oxidative damage to cells. Cells have a number of defense
      mechanisms to protect themselves from the toxicity of ROS. Even though, there are
      studies portraying the role of free radicals in bone loss, the defense mechanism
      adapted by bone in ovariectomized animals remains obscure. We investigated the
      impact of ovariectomy (OVX) on the bone antioxidant system in rats. METHODS:
      Sixty days after bilateral OVX, the rats were killed and the femora were removed,
      the tissue homogenates were made and used for the estimation of superoxide
      dismutase (SOD), glutathione peroxidase (GPx), glutathione S transferase (GST),
      lipid peroxidation (LPO) and hydrogen peroxide (H(2)O(2)). RESULTS: The levels of
      LPO and H(2)O(2) were increased and enzymatic antioxidants like SOD, GPx, GST
      were decreased in ovariectomized animals when compared to sham-operated control
      rats. The calculated correlation coefficient demonstrated strong correlation
      (0.905) between the production of H(2)O(2) and LPO in the femur bone. A strong
      inverse (-0.945) correlation was observed between H(2)O(2) production and SOD
      activity. CONCLUSIONS: OVX induces oxidative stress in the femur bone of rats.

PMID- 15970280
TI  - Monitoring insulin-like growth factors in HIV infection and AIDS.
AB  - There is a close association between the growth hormone (GH)-insulin-like growth
      factor I (IGF-I) axis, infection and immunity. Infection with the human
      immunodeficiency virus (HIV) is often associated with a decrease of the
      concentrations of IGF-I, IGF-II, IGF-binding protein 3 (IGFBP-3) and an increase
      of IGFBP-1 and -2. Many investigators have studied the relationship between the
      GH-IGF-I system and some of the most common characteristics of disease
      progression, such as decreased CD4 cell counts, weight loss and fat
      redistribution. Although conditions for restoration of thymic function and
      lymphopoiesis with GH or IGF-I are still not well defined, many studies led to
      the development of clinical trials on the therapeutic use of GH, IGF-I and GHRH
      for the treatment of weight loss or fat redistribution, two problems which
      persist despite the introduction of highly active antiretroviral therapy.
      Monitoring IGF-I concentrations during treatment with GH and GHRH is likely to
      become an essential component of their therapeutic use. IGF-I levels are the
      first indicator of treatment efficacy and can be used to monitor compliance. High
      levels of IGF-I are a warning sign for the increased risk of potential adverse
      effects, such as acromegalic-like symptoms or malignancy. This could lead to a
      reduction of the therapeutic dose or the temporary interruption of treatment
      until IGF levels reach a safe range. IGF-I levels are also likely to increase
      with other hormones used in HIV patients, such as erythropoietin for the
      treatment of anemia or anabolic androgens in HIV-infected women.

PMID- 15970281
TI  - Proteome analysis in the clinical chemistry laboratory: myth or reality?
AB  - BACKGROUND: We review here modern aspects of proteomic analysis, as displayed via
      orthogonal mass/charge analysis (isoelectric focusing in the first dimension,
      followed by sodium dodecyl sulphate electrophoresis in polyacrylamide gels, SDS
      PAGE, at right angles, in the second dimension). METHODS: This technique is
      capable of displaying a few thousand polypeptide chains, characterized by a
      single pI and M(r) value as coordinates, and recognized via elution, digestion
      and mass spectrometry analysis. Although, up to the present, this technique has
      been used mostly for advanced research, with no immediate applications in the
      clinical chemistry laboratory, there are hints that such applications will soon
      become a reality. RESULTS AND CONCLUSIONS: In the field of cancer research, it is
      here shown that stathmin (Op18) becomes heavily phosphorylated in cancerous
      mantle cell lymphomas and that the progression of the disease can be followed by
      the progression of phosphorylation of Op18 and by the appearance of additional
      phosphorylated spots. Also chemoresistance of different tumors has been evaluated
      via 2D-PAGE through quantitative, differential proteomics: among up- and down
      regulated proteins in a human cervix squamous cell carcinoma cell line (A431),
      rendered resistant to cisplatin, one particular protein was found to appear in
      large quantities by de novo synthesis: 14-3-3, a protein known to impart
      resistance to apoptosis to cells. In the field of brain disorders, we could set
      up an easy test for detecting pathological prions in sporadic Creutzfeldt-Jakob
      disease (sCJD), by simply searching for those pathological forms in the olfactory
      mucosa (up to this finding, diagnosis could only be confirmed post-mortem). We
      are currently working on a test for differentiating sCJD from all the other
      degenerative dementias. Upon 2D mapping of cerebrospinal fluid (CSF) and
      immunoblot analysis, we could identify a major spot (pI 4.8, M(r) 30 kDa)
      followed by some two-three minor spots (pIs 5.0-6.0, same M(r) value) of the same
      14-3-3 anti-apoptotic protein involved in chemoresistance. By this test, sCJD
      could be differentiated from all the other degenerative dementias, which are 14-3
      3 negative (in sCJD, the rapid and massive brain cell damage releases large
      quantities of 14-3-3 in the cerebrospinal fluid). Another protein that appears
      very promising as a marker for sCJD is cystatin C, that is strongly up-regulated
      in this pathology. Human sera should also be mined for discovery of many more
      markers for disease. Up to the present, no one could be found, but this was due
      to the presence of several major proteins, obscuring all rare ones. Via several
      immuno-subtraction steps, followed by ion exchange and size exclusion
      chromatography, one can now detect proteins and peptides present in sera at
      levels below 10 ng/mL, highlighting the road to discovery of novel markers of
      disease. Another technique that could revolutionize biomarker discovery in
      biological fluids consists in the use of combinatorial beads to reduce the
      dynamic range. They consist in a library of combinatorial ligands coupled to
      small beads. Such a library comprises hexameric ligands composed of amino acids,
      resulting in millions different structures. When these beads are impregnated with
      complex proteomes (e.g., human sera, CSF, urines) of widely differing protein
      compositions, they are able to significantly reduce the concentration
      differences, thus greatly enhancing the possibility of evidencing low-abundance
      species.

PMID- 15970282
TI  - The role of proteomics in the assessment of premature rupture of fetal membranes.
AB  - The presence and integrity of amniotic fluid is fundamental for the normal
      development of the human fetus during pregnancy. Its production rate changes
      throughout pregnancy and is mainly related to the functions of the different
      fetal, placental and amniotic compartments. Premature rupture of the membranes
      (PROM) occurs in about 5% of deliveries, with complications such as infection and
      preterm birth. The management of patients with PROM, regardless of gestational
      age, remains controversial, and it is therefore important to develop new
      biological tests in order to achieve accurate diagnoses by identifying the
      presence of specific amniotic fluid markers in vaginal environment. We recently
      showed the usefulness of amniotic fluid proteomics in identifying a series of
      peptides that were absent from the corresponding maternal plasma. Several
      peptides corresponded to fragments of plasma proteins. Two peptides, absent from
      plasma samples of pregnant women, were identified in amniotic fluid. They
      corresponded to the COOH-terminal parts of perlecan (SwissProt: P98160) and of
      agrin (SwissProt: O00468) protein cores, two major heparan sulfate proteoglycans
      of basement membranes. In this review we will discuss modern proteomic strategies
      that may improve the laboratory assessment of PROM, and will focus on some of the
      biochemical characteristics of agrin and perlecan fragments identified in
      amniotic fluid.

PMID- 15970283
TI  - Apoptosis signal-regulating kinase 1 in leukotriene D(4)-induced activator
      protein-1 activation in airway smooth muscle cells.
AB  - Cysteinyl leukotrienes (LTs) are involved in allergic disorders including
      bronchial asthma. Transcription factor activator protein-1 (AP-1) activation is
      essential for cell proliferation and differentiation. LTD(4) is shown to promote
      human airway smooth muscle cell proliferation; however, the effect of LTD(4) on
      AP-1 activation in airway smooth muscle cells and the molecular mechanism in
      regulating AP-1 activation have not been determined. We examined the effect
      LTD(4) on AP-1 activation in human airway smooth muscle cells and analyzed a role
      of apoptosis signal-regulating kinase1 (ASK1), an upstream kinase kinase of c-Jun
      NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in
      LTD(4)-induced AP-1 activation to clarify the signaling molecule regulating AP-1
      activation. The results showed that LTD(4) induced AP-1 activation determined by
      AP-1-dependent luciferase gene activity and ASK1 phosphorylation. Transient
      transfection of the dominant negative form of ASK1 attenuated LTD(4)-induced AP-1
      activation. In addition, LTD(4)-induced AP-1 activity was depressed in the
      dominant negative form of ASK1-stably transfected porcine artery endothelial
      cells compared to that in the parental porcine artery endothelial cells. These
      results indicate that LTD(4) is capable of inducing AP-1 activation and ASK1
      regulates AP-1 activation in LTD(4)-stimulated airway smooth muscle cells.

PMID- 15970284
TI  - Anti-inflammatory and analgesic effects of atorvastatin in a rat model of
      adjuvant-induced arthritis.
AB  - Statins exert favorable effects on lipoprotein metabolism but may also possess
      anti-inflammatory effects. Here, we explored the effects of atorvastatin in a
      model of adjuvant-induced arthritis in rat. Oral treatment with atorvastatin (1
      10 mg/kg) from days 10 to 15 after arthritis induction caused inhibition of the
      increase in paw volume. Maximal inhibition occurred at a dose of 10 mg/kg. At
      this dose, atorvastatin markedly ameliorated the histopathological findings of
      joints obtained from day 16 of arthritic animals. This was mirrored by an
      effective blockade of neutrophil influx, as assessed by the tissue
      myeloperoxidase levels. The concentrations of the cytokines interleukin-1beta,
      interleukin-6 and tumor necrosis factor-alpha and the chemokines CCL5 and CCL2
      were significantly decreased in arthritic rats treated with atorvastatin. In
      contrast, the levels of interleukin-10 were enhanced by the drug treatment. The
      drug also prevented the hypernociception observed in the inflamed joints. These
      data clearly illustrate the therapeutic potential of a statin-sensitive pathway
      in inflammatory arthritis.

PMID- 15970285
TI  - [Pt(HPxSC)Cl(3)], a novel platinum(IV) compound with anticancer properties.
AB  - There has been a continuing effort for the discovery of novel platinum(IV)-based
      antitumor compounds with better therapeutic performances than cisplatin. In the
      present work, the anticancer action of recently synthesized Pt(IV)-based complex
      [Pt(HPxSC)Cl(3)] was investigated using rat and human astrocytoma cell lines C6
      and U251. [Pt(HPxSC)Cl(3)] markedly reduced the number of cultured astrocytoma
      cells (IC(50), 80 microM), as determined by crystal violet assay. The Pt(IV)
      complex induced apoptotic death of tumor cells, as flow cytometry analysis of the
      propidium iodide-stained cellular DNA revealed approx. 30% of hypodiploid cells
      in [Pt(HPxSC)Cl(3)]-treated astrocytoma cell cultures. On the other hand,
      [Pt(HPxSC)Cl(3)] at 200 microM did not affect the viability of rat primary
      astrocytes, unlike the established anticancer drug cisplatin, which displayed
      high toxicity toward both astrocytoma cells (IC(50), 15 microM) and primary
      astrocytes (IC(50), 20 microM). Moreover, [Pt(HPxSC)Cl(3)] at 100 microM did not
      interfere with the ability of rat peritoneal macrophages to produce important
      antitumor molecules nitric oxide and tumor necrosis factor-alpha. Finally, we
      assessed the ability of [Pt(HPxSC)Cl(3)] to restrain growth of some bacterial and
      yeast strains, but it showed rather limited antimicrobial activity.

PMID- 15970286
TI  - Leishmania major and Leishmania tropica: I the in vitro effects of an
      immunomodulator, S2-Complex.
AB  - This study was undertaken to try to determine the possible anti-leishmanial
      activity of S2-Complex, an organic complex of copper chloride, ascorbic acid, and
      nicotinamide. The promastigotes, axenic amastigotes, and intracellular
      amastigotes of both Leishmania major and Leishmania tropica were incubated with
      different concentrations of S2-Complex. The EC50 for each form was calculated.
      Results show that all forms of the parasites were dose dependently inhibited by
      S2-Complex. The promastigotes of both parasites were the most resistant with
      highest EC50 followed by axenic amastigotes. While intracellular amastigotes were
      the most sensitive with the lowest EC50. These results indicate that S2-Complex
      has a direct anti-leishmanial effect. When mice were treated with S2-Complex or
      BCG for four days before harvesting the macrophages, and the macrophages infected
      with both L. major and L. tropica, they showed increased phagocytosis and
      increased parasite killing. The results of S2-Complex were not statistically
      different from the immunomodulating agent BCG. These results indicate that S2
      Complex has an immunomodulating effect in addition to the direct anti-leishmanial
      effect.

PMID- 15970287
TI  - Color Doppler evaluation of blood flow changes in leiomyomas after uterine artery
      ligation.
AB  - OBJECTIVE: To detect possible changes in main blood vessels within leiomyomas
      after uterine artery ligation using color Doppler sonography. METHOD: Blood flow
      in main leiomyoma blood vessels was measured before and after the procedure in 14
      women who also had abnormal uterine bleeding, pelvic pain or pressure, and/or
      anemia. RESULTS: Of the 14 patients, 13 reported complete disappearance of
      preoperative pain or pressure and 1 reported significant relief. Within 1 week to
      4 months after uterine artery ligation, major blood flow within leiomyomas had
      significantly decreased in all patients. Eight months after the procedure, 1 of
      the women became pregnant. CONCLUSION: Laparoscopic uterine artery ligation via a
      lateral retroperitoneal technique is a safe and effective treatment for
      leiomyomas. Color Doppler sonography verified the ability of the procedure to
      diminish blood flow within leiomyomas in all patients.

PMID- 15970288
TI  - Sonographic dating of twin pregnancy using singleton data.

PMID- 15970289
TI  - Anal incontinence among women with one versus two complete third-degree perineal
      lacerations.
AB  - OBJECTIVE: To compare the rate of anal incontinence and severe incontinence among
      women who had 0, 1, and > or =2 additional vaginal deliveries after sustaining a
      third-degree perineal laceration and between subjects with one versus two third
      degree tears. METHOD: A telephone survey was done to assess the anal function of
      all subjects who sustained a complete third-degree tear as a nullipara. RESULT:
      The rate of anal incontinence and severe incontinence was similar among women who
      had 0, 1, and > or =2 additional deliveries (11/65, 11/67, and 12/40, p=0.179;
      2/65, 1/67, and 2/40, p=0.811) and between women who had one sphincter tear and
      no additional delivery versus those with two tears and > or =2 subsequent
      deliveries (11/65 and 10/37, p=0.225. 2/65 and 2/37, p=0.460). CONCLUSION:
      Additional vaginal deliveries and a repeat sphincter tear after the initial third
      degree laceration were not associated with a higher rate or severity of anal
      incontinence.

PMID- 15970290
TI  - Efficacy of tibolone and transdermal estrogen therapy on psychological symptoms
      in women following surgical menopause.
AB  - OBJECTIVE: This study investigated the efficacy of tibolone and transdermal
      estradiol therapy on menopausal and psychological symptoms in women following
      surgical menopause. METHOD: Seventy-five women who had undergone surgical
      menopause were randomized to a 6-month double-blind interventional study
      treatment with oral 2.5 mg/day tibolone, transdermal 3.9 mg/week estradiol or
      oral placebo. The patients were assessed using Kupperman's Scale, Hamilton
      Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale (HARS) before
      and at the end of the 6 months of treatment. RESULT: Sixty-five subjects
      completed the study: 23 on tibolone, 21 on transdermal estradiol and 21 on
      placebo. At the end of the 6 months of therapy, highly significant improvements
      in menopausal symptoms, depression and anxiety scores were observed in both
      groups (tibolone and transdermal estradiol groups) as compared with baseline
      values (p<0.001). However, in the placebo group, there were no significant
      differences on changes from baseline to the end of treatment (p>0.05).
      CONCLUSION: These results suggest that tibolone and transdermal estradiol therapy
      significantly improve menopausal and psychological symptoms in women following
      surgical menopause.

PMID- 15970291
TI  - Effects of raloxifene, hormone therapy, and soy isoflavone on serum high
      sensitive C-reactive protein in postmenopausal women.
AB  - OBJECTIVE: To compare the effects of raloxifene, estradiol valerate plus
      dienogest, and soy isoflavones (genistein) on serum concentrations of high
      sensitive C-reactive protein in healthy postmenopausal women. METHODS: The 80
      healthy postmenopausal women enrolled in the study were randomly allocated to
      receive 60 mg of raloxifene, 2 mg of estradiol valerate plus dienogest, 40 mg of
      genistein, or placebo (n=20 in each group). Blood samples were collected at the
      start of the study and at 3 and 6 months. Lipid profile was also determined.
      RESULTS: Only the group receiving estradiol valerate plus dienogest showed an
      increase in serum levels of high-sensitive C-reactive protein compared with
      baseline values and values in the control and other groups. All 3 treatments
      resulted in an increase in high-density lipoprotein cholesterol levels and a
      decrease in total, low-density, and very-low-density lipoprotein cholesterol
      levels. CONCLUSIONS: Estradiol valerate plus dienogest, but not raloxifene and
      genistein, increase serum high-sensitive C-reactive protein levels. All 3
      treatments, however, have an estrogen-like effect on serum lipid profile.

PMID- 15970292
TI  - Risky procedures by nurses in hospitals: problems and (contemplated) refusals of
      orders by physicians, and views of physicians and nurses: a questionnaire survey.
AB  - Occurrence of problems with, refusals of orders and contemplated refusals of
      orders for risky procedures by nurses in Dutch hospitals and views on the safety
      of performance was studied using postal questionnaires (600 physicians and 3200
      nurses, response 60--71%). Of the respondents, 11--30% experienced problems with
      and (contemplated) refusals of orders for risky procedures in the previous 12
      months. Gynaecologists and internists most frequently mentioned problems
      concerning the practical performance of the procedure (44% and 30%,
      respectively). The reason for a problem or a contemplated refusal most frequently
      given by nurses was that they disagreed with the medication policy (34% and 35%,
      respectively). The reason for a refusal most frequently given by the
      gynaecologists, internists, and nurses was that the nurses themselves were of the
      opinion that they did not have the necessary authorisation (95%, 67%, and 62%,
      respectively). With regard to certain procedures, the views of professionals are
      more strict than the current legal regulations.

PMID- 15970293
TI  - Murine immune responses to a novel schistosome egg antigen, SmEP25.
AB  - Pathology in schistosomiasis consists of granuloma formation around parasite
      eggs. There is considerable variation in the severity of disease in individuals
      with schistosomiasis, which may result from differential responses to egg
      antigens. The egg-induced immunopathology is mediated by CD4+ T helper cells
      sensitised to egg antigens. In this study, cellular responses to a 25-kDa
      fraction of egg proteins identified a novel T-cell antigen, SmEP25. The native
      SmEP25 elicited significant proliferative responses as well as gamma interferon
      (IFN-gamma), IL-2, IL-4, and IL-5 secretion in CD4+ cells from 8.5-week infected
      CBA and C57BL/6 mice. In C57BL/6 mice, proliferative responses to SmEP25 were
      relatively stronger than those directed against the major egg antigen Sm-p40,
      whereas in CBA mice the reverse was found. SmEP25 elicited stronger Th2 type
      response than Sm-p40 in both mouse strains. By comparison, recombinant SmEP25
      elicited a smaller, Th1-polarised response, with significant IFN-gamma, low
      levels of IL-5 and essentially no IL-4. B-cell responses to SmEP25 coincided with
      the start of parasite egg production and SmEP25 protein was restricted to
      parasite eggs. The systematic identification of T-cell-sensitising egg components
      will lead to a better understanding of the processes involved in granuloma
      formation.

PMID- 15970294
TI  - Human scavenger receptor class B type I is expressed with cell-specific fashion
      in both initial and terminal site of reverse cholesterol transport.
AB  - The reverse cholesterol transport (RCT) is one of the major protective systems
      against atherosclerosis, in which high-density lipoprotein (HDL) removes
      cholesterol from lipid-laden cells and delivers it to the liver. Scavenger
      receptor class B type I (SR-BI) is a HDL receptor in the liver and adrenal glands
      and is involved in the selective uptake of cholesteryl ester from HDL, which has
      been extensively, analyzed using rodent models. However, the expression and
      regulation of the human homologue of this receptor are not known yet. We
      previously reported that this receptor is expressed in in vitro differentiated
      macrophages and its expression is up-regulated by the addition of modified
      lipoproteins into the medium [Hirano K, Yamashita S, Nakagawa Y, et al.
      Expression of human scavenger receptor class B type I in cultured human monocyte
      derived macrophages and atherosclerotic lesions. Circ Res 1999;85:108-16]. In
      order to further investigate the physiological significance of this receptor in
      humans, we have performed extensive immunohistochemical analyses with specimens
      of the liver and adrenal glands as well as arteries with different stages of
      atherosclerotic lesions. In human liver and adrenal glands, a positive SR-BI
      immunoreactivity was detected in both hepatic and adrenal parenchymal cells as
      well as Kupffer cells. These parenchymal cells had a strong signal on the cell
      surface, whereas Kupffer cells showed a heterogeneous and punctate pattern. In
      human aorta and coronary arteries, SR-BI was highly expressed in atherosclerotic
      plaques, but not in non-atherosclerotic lesions. Double immunostaining revealed
      that SR-BI was expressed in a subpopulation of macrophages, of which staining
      pattern was similar to that observed in Kupffer cells. These data clearly
      demonstrated that SR-BI was expressed with cell-specific fashions in both the
      initial and terminal step of RCT in humans. Thus, SR-BI might be physiologically
      relevant and have distinct tissue-specific functions.

PMID- 15970295
TI  - A five-link 2D brachiating ape model with life-like zero-energy-cost motions.
AB  - We have found periodic life-like brachiating motions of a rigid-body ape model
      that use no muscle or gravitational energy to move steadily forward. The most
      complicated of these models has 5 links (a body and two arms, each with 2 links)
      and 7 degrees of freedom in flight. The defining feature of all our periodic
      solutions is that all collisions are at zero relative velocity. These motions are
      found using numerical integration and root-finding that is sufficiently precise
      so as to imply that the solutions found correspond to mathematical solutions with
      exactly zero energy cost. The only actuation and control in the model is for
      maintaining contact with and releasing handholds which requires no mechanical
      work. The similarity of these energy-free simulations to the motions of apes
      suggests that muscle-use minimization at least partially characterizes the
      coordination strategies they use.

PMID- 15970296
TI  - Immuno-stimulating effect of the endo-polysaccharide produced by submerged
      culture of Inonotus obliquus.
AB  - Inonotus obliquus BELYU1102 was selected from 12 different strains of Inonotus as
      a producer of immuno-stimulating polysaccharide. After a batch fermentation of I.
      obliquus BELYU1102 was carried out in a 300 l pilot vessel, endo-polysaccharide
      and exo-polysaccharide were both obtained. The proliferation activity of endo
      polysaccharide for splenic cells was much higher than the activity of exo
      polysaccharide. The active endo-polysaccharide was produced primarily during the
      late stationary phase. Enhanced proliferation and polyclonal IgM antibody
      production were observed in B cells by purified water-soluble endo
      polysaccharide. Nitrite production and expression of IL-1beta, IL-6, TNF-alpha,
      and iNOS in macrophages were also enhanced. However, the endo-polysaccharide did
      not affect the proliferation of T cells, the IL-2 expression of Th1 cells, or the
      IL-4 expression of Th2 cells. The endo-polysaccharide showed activities similar
      to lipopolysaccharide (LPS) for B cells and macrophages, but there was a large
      difference between the two polysaccharides because cellular activations induced
      by endo-polysaccharide were not affected by polymyxin B, a specific inhibitor of
      LPS. The endo-polysaccharide appeared to have other cellular binding sites with
      TLR-4 and did not show a direct toxicity against tumor cells. However, indirect
      anti-cancer effects via immuno-stimulation were observed. The mycelial endo
      polysaccharide of I. obliquus is a candidate for use as an immune response
      modifier. Submerged mycelial cultures are advantageous for industrial production
      of polysaccharides.

PMID- 15970297
TI  - Impaired expression of PPAR gamma protein contributes to the exaggerated growth
      of vascular smooth muscle cells in spontaneously hypertensive rats.
AB  - Peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the
      nuclear receptor family, has been implicated in the regulation of vascular smooth
      muscle cell (VSMC) growth; however, the underlying mechanisms are still not fully
      understood. We hypothesized that PPAR gamma functional deficiency may contribute
      to the enhanced proliferation of VSMC associated with hypertension in
      spontaneously hypertensive rats (SHR). We observed that PPAR gamma mRNA level in
      SHR VSMC was 3 approximately 4 fold higher than that from Wistar-Kyoto rats
      (WKY), but the protein expression levels of PPAR gamma are significantly lower in
      SHR than WKY VSMC, suggesting an impaired control of PPAR gamma protein
      expression in SHR VSMC. The deficiency of PPAR gamma protein expression in SHR
      VSMC was demonstrated by PPAR gamma reporter gene assays. Furthermore, the
      exaggerated growth of SHR VSMC was markedly attenuated by adenoviral PPAR gamma
      overexpression. Taken together, our results provided the first direct evidence
      that impaired expression of PPAR gamma protein contributes to the exaggerated
      growth of SHR VSMC.

PMID- 15970299
TI  - Isolation and preliminary characterization of a 22-kDa protein with trypsin
      inhibitory activity from toad Bufo andrewsi skin.
AB  - A novel trypsin inhibitor termed BATI was purified to homogeneity from the skin
      extracts of toad Bufo andrewsi by successive ion-exchange, gel-filtration and
      reverse-phase chromatography. BATI is basic single chain glycoprotein, with
      apparent molecular weight of 22 kDa in SDS-PAGE. BATI is a thermal stable
      competitive inhibitor and effectively inhibits trypsin's catalytic activity on
      peptide substrate with the inhibitor constant (K(i)) value of 14 nM and shows no
      inhibitory effect on chymotrypsin, thrombin and elastase. The N-terminal sequence
      of BATI is EKDSITD, which shows no similarity with other known trypsin
      inhibitors.

PMID- 15970298
TI  - Alleviation of aflatoxin B1-induced oxidative stress in HepG2 cells by volatile
      extract from Allii Fistulosi Bulbus.
AB  - The volatile extract from Allii Fistulosi Bulbus (VEAF) was isolated by steam
      distillation under reduced pressure, followed by continuous liquid-liquid
      extraction, and its effects on aflatoxin B1 (AFB1)-induced oxidative stress were
      investigated in human hepatoma cells (HepG2). The main constituents of the VEAF,
      identified by gas chromatography/mass spectrometry, were 2-octyl-5-methyl-3(2H)
      furanone, 2-hexyl-5-methyl-3(2H)-furanone, 2,5-dimethylthiophene, 3,5-diethyl
      1,2,4-trithiolane and 3,4-dimethyl-2,5-dihydro-thiophene-2-one. VEAF
      significantly inhibited the formation of intracellular reactive oxygen species
      caused by AFB1 in a dose-dependent manner, concomitant with a significant
      decrease in the AFB1-induced cytotoxicity. VEAF pretreatment significantly
      reduced the levels of thiobarbituric acid reactive substances, an indicator of
      lipid peroxidation, whereas increased the level of reduced glutathione. The level
      of 8-hydroxy-2'-deoxyguanosine, a DNA oxidative stress marker, was also decreased
      by 49-59% with pretreatment of VEAF. With respect to the activity of AFB1
      metabolizing enzymes, VEAF significantly increased the activity of glutathione S
      transferase, and significantly decreased the cytochrome (CYP) P450 3A4 activity,
      but had a little effect on the CYP1As. These results suggest that VEAF may be
      selectively effective in alleviating the AFB1-induced oxidative stress, and lead
      to cytoprotection against AFB1 exposure.

PMID- 15970300
TI  - 1H NMR quantification in very dilute toxin solutions: application to anatoxin-a
      analysis.
AB  - A complete procedure is described for the extraction, detection and
      quantification of anatoxin-a in biological samples. Anatoxin-a is extracted from
      biomass by a routine acid base extraction. The extract is analysed by GC-MS,
      without the need of derivatization, with a detection limit of 0.5 ng. A method
      was developed for the accurate quantification of anatoxin-a in the standard
      solution to be used for the calibration of the GC analysis. 1H NMR allowed the
      accurate quantification of microgram quantities of anatoxin-a. The accurate
      quantification of compounds in standard solutions is rarely discussed, but for
      compounds like anatoxin-a (toxins with prices in the range of a million dollar a
      gram), of which generally only milligram quantities or less are available, this
      factor in the quantitative analysis is certainly not trivial. The method that was
      developed can easily be adapted for the accurate quantification of other toxins
      in very dilute solutions.

PMID- 15970301
TI  - Localization of epitopes in the toxins of Tityus serrulatus scorpions and
      neutralizing potential of therapeutic antivenoms.
AB  - Overlapping pentadecapeptides covering the complete amino acid sequence of TsII,
      TsVII and TsIV toxins from the venom of scorpion Tityus serrulatus (Ts), were
      prepared by use of the Spot method of multiple peptide synthesis. Horse anti-Ts
      antisera for therapeutic use were tested for their binding to peptides. All nine
      antisera tested showed reactivity with several peptides from the three toxins.
      Three antigenic regions, one in the very N-terminal, the second in the central
      part and the other in the C-terminal part of the three toxins were frequently,
      but not constantly recognized, with an intensity that seemed to be related to the
      neutralizing potency of the tested antivenom. Thus the corresponding peptides
      (residues 1-15 and 48-62 of TsII; residues 1-15, 16-30 and 48-62 of TsIV and
      residues 1-15 and 47-61 of TsVII) were synthesized, coupled to KLH and used as
      antigens to coat the microtitration plates to determine any relationship between
      their ELISA reactivity with therapeutic horse antivenoms and the neutralizing
      potential of these antivenoms. The mixture of the N-terminal peptide of TsII, of
      the N-terminal TsVII peptide and of the C-terminal of TsIV was found to give a
      linear relationship with the neutralizing titer of horse serum of low
      neutralizing potency (< or =1 mg/ml). However, high neutralizing antivenoms did
      not show the expected response in peptide ELISA. This observation is discussed in
      the context of the occurrence of continuous and discontinuous epitopes on toxins.

PMID- 15970302
TI  - Neurotoxic and myotoxic actions from Lachesis muta muta (surucucu) whole venom on
      the mouse and chick nerve-muscle preparations.
AB  - Lachesis genus is one of the less studied among others from Viperidae's genera,
      mainly due to difficulties in obtaining the venom. Accidents by Lachesis snakes
      cause severe envenoming syndrome, eventually leading victims to shock. This work
      is part of a comprehensive study aimed at studying the venom and its effects.
      Herein the neurotoxicity and myotoxicity of L. muta muta venom were investigated
      on mouse phrenic nerve-diaphragm (PNDp) and chick biventer cervicis (BCp)
      preparations. For both preparations the time required to venom produces 50%
      neuromuscular blockade was indirectly concentration-dependent, being for PNDp:
      117.6+/-6.5 min (20 microg/ml), 70.1+/-8.6 min (50 microg/ml) and 43.6+/-3.8 min
      (100 microg/ml), and for BCp: 28+/-1.8 min (50 microg/ml), 30.4+/-2.3 min (10
      microg/ml), 50.4+/-4.3 min (5 microg/ml) and 75.2+/-0.7 min (2 microg/ml),
      (n=5/dose). In BCp, a venom dose of 50 microg/ml significantly reduced
      contractures elicited by exogenous acetylcholine (55 microM) and KCl (20 mM), as
      well as increased the release of creatine kinase (442.7+/-39.8 IU/l in controls
      vs 4322.6+/-395.2 IU/l, after 120 min of venom incubation (P<0.05).
      Quantification of myonecrosis in BCp indicated the doses 50 and 10 microg/ml as
      significantly myotoxic affecting 59.7+/-6.2%, and 20.8+/-1.2% of fibers,
      respectively, whereas 5 and 2 microg/ml that affected 13.5+/-0.8% and 5.4+/-0.6%
      of fibers, were considered weakly- and non-myotoxic, respectively. We concluded
      that there are neurotoxins present in the venom, the concentration of which
      governs its pre- (if low) or postsynaptic (if high) activity. Since myotoxicity
      in the avian preparation is negligible at lower venom doses, but not
      neurotoxicity, we suggest that this effect may contribute minimum to the venom
      neurotoxic effect. The BCp is more sensible than PNDp to Lachesis m. muta venom.

PMID- 15970303
TI  - Myotoxic and cytolytic activities of dimeric Lys49 phospholipase A2 homologues
      are reduced, but not abolished, by a pH-induced dissociation.
AB  - Lys49 phospholipase A2 (PLA2) homologues are myotoxic proteins devoid of
      catalytic activity. Their toxic determinants map to the C-terminal region 115
      129, which plays an effector role in membrane damage. The dimeric state was
      reported to be essential for a Lys49 PLA2 which lost its liposome-disrupting
      activity after dissociating into monomers at pH 5.0. This study, evaluated the
      effects of a pH-induced dissociation on the toxicity of four Lys49 PLA2s, using
      biological targets instead. Both their cytolytic and myotoxic activities were
      lower at pH 5.0 than at pH 7.2. However, in contrast with experiments using
      artificial bilayers, toxic effects upon biological targets were not abolished at
      pH 5.0. Importantly, C-terminal synthetic peptides of two Lys49 PLA2s also showed
      lower cytolytic action at pH 5.0 than at pH 7.2, indicating that factors other
      than the dimeric/monomeric state of the proteins may also be involved in these
      differences of toxicity. Results support the view that the dimeric state of Lys49
      PLA2s could play an enhancing, although not essential role, in their C-terminal
      region-mediated mechanism of myotoxicity.

PMID- 15970304
TI  - Modulation of nicotinic acetylcholine and N-methyl-d-aspartate receptors by some
      Hymenopteran venoms.
AB  - The effect of 19 venoms from solitary wasps, solitary bees, social wasps and ants
      were investigated for their effects on nicotinic acetylcholine receptors (nAChR)
      and ionotropic glutamate receptors (IGRs) of both the N-methyl-d-aspartate
      (NMDAR) and non-NMDAR type. Whole-cell patch clamp of human muscle TE671 cells
      was used to study nAChR, and of rat cortical and cerebellar granule cells for
      IGRs. Solitary wasp venoms caused significant voltage-dependent antagonism of
      nAChR responses to 10 microM ACh and NMDAR responses to 100 microM NMDA (+10
      microM glycine) when co-applied at 1 microg/ml with the agonists. At positive
      holding potentials (V(H)) potentiation of these receptors was observed with some
      venoms. Solitary bee venoms only affected nAChR by causing either voltage
      independent antagonism or potentiation of their responses to 10 microM ACh. Of
      four social wasp venoms, one acted on nAChR by potentiating responses to 10 ACh,
      while another generated an ACh-like response when applied alone. They had no
      effect on IGRs. Of the two ant venoms, one caused voltage-independent inhibition
      of nAChR. Neither affected IGRs. The data indicate the presence of nAChR agonists
      and antagonists and NMDAR antagonists in Hymenopteran venoms and warrant further
      investigation to separate and identify these venom components.

PMID- 15970305
TI  - Controlling biofouling caused by the colonial hydroid Cordylophora caspia.
AB  - The euryhaline hydroid, Cordylophora caspia, causes fouling problems in Europe
      and the United States. Researchers propose that this hydroid is becoming more
      prevalent in freshwater habitats as evidenced in Morris, IL where it was found
      clogging intake pipes and screens at a power plant, Midwest Generation's Collins
      Station. Our objective was to determine ways to curtail growth or kill C. caspia.
      Hydroid colonies in the laboratory were exposed to thermal treatments of 35,
      36.1, 37.7, and 40.5 degrees C ranging from 1 to 8h. Hydroids did not survive at
      the two highest temperatures. Colonies exposed to lower temperatures exhibited
      varying degrees of survival relative to temperature and exposure time and
      demonstrated regeneration. In addition, experiments using chlorine were conducted
      using concentrations ranging from 0.2 to 5.0 mgl(-1). Chlorine experiments using
      exposure times of 105 min and three 20 min exposures in a 24h period did not kill
      colonies but were effective in curtailing growth. Thermal treatments are
      preferred because they are effective and result in less environmental impact in
      receiving waters than chemicals.

PMID- 15970306
TI  - Asymmetric transesterification of secondary alcohols catalyzed by feruloyl
      esterase from Humicola insolens.
AB  - A new asymmetric transesterification of secondary alcohols catalyzed by feruloyl
      esterase from Humicola insolens has been found. Although alcohols are not the
      natural substrates for this enzyme, a high R enantioselectivity was observed.
      Stereochemical studies showed that variations in substrate structure lead to
      strong variations in enantioselectivity. The highest enantioselectivities are
      obtained when the beta-carbon of the secondary alcohol is tertiary or quaternary.

PMID- 15970307
TI  - Solubilization of DNAPLs by mixed surfactant: reduction in partitioning losses of
      nonionic surfactant.
AB  - Efforts to remediate the dense nonaqueous phase liquids (DNAPLs) by mobilizing
      them face with risks of driving the contaminants deeper into aquifer zones. This
      spurs research for modifying the approach for in situ remediation. In this paper,
      a novel solubilization of DNAPLs by mixed nonionic and anionic surfactant, Triton
      X-100 (TX100) and sodium dodecylbenzene sulfonate (SDBS), was presented and
      compared with those by single ones. Given 1:40 phase ratio of DNAPL:water (v/v)
      and the total surfactant concentration from 0.2 to 10gl(-1), mixed TX100-SDBS at
      the total mass ratios of 3:1, 1:1 and 1:3 exhibited significant solubilization
      for the DNAPLs, trichloroethene (TCE), chlorobenzene (CB) and 1,2-dichlorobenzene
      (1,2-DCB). The solubilization extent by mixed TX100-SDBS was much larger than by
      single TX100 and even larger than by single SDBS at the ratios of 1:1 and 1:3,
      respectively. TX100 partitioning into the organic phase dictated the
      solubilization extent. The TX100 losses into TCE, CB and 1,2-DCB phases were more
      than 99%, 97% and 97% when single TX100 was used. With SDBS alone, no SDBS
      partitioned into DNAPLs was observed and in mixed systems, SDBS decreased greatly
      the partition loss of TX100 into DNAPLs. The extent of TX100 partition decreased
      with increasing the amount of SDBS. The mechanism for reduction of TX100
      partition was discussed. TX100 and SDBS formed mixed micelles in the solution
      phase. The inability of SDBS to partition into DNAPLs and the mutual affinity of
      SDBS and TX100 in the mixed micelle controlled the partitioning of TX100 into
      DNAPL phase. The work presented here demonstrates that mixed nonionic-anionic
      surfactants would be preferred over single surfactants for solubilization
      remediation of DNAPLs, which could avoid risks of driving the contaminants deeper
      into aquifers and decrease the surfactant loss and remediation cost.

PMID- 15970308
TI  - The role of SBR mixed liquor volume exchange ratio in aerobic granulation.
AB  - Four sequencing batch reactors (SBR) were operated at different volume exchange
      ratios of 20-80%. Results showed that a rapid aerobic granulation could be
      achieved in SBR run at high volume exchange ratios, and the characteristics of
      mature aerobic granules in terms of mean size, SVI, granule fraction, EPS and
      calcium content were all closely related to the volume exchange ratio applied to
      SBR. To interpret the role of volume exchange ratio in aerobic granulation, a
      concept of minimum settling velocity of bioparticles was proposed, which is the
      function of both settling time and volume exchange ratio. It was further
      demonstrated that the effect of volume exchange ratio on aerobic granulation in
      SBR would be realized through selecting the minimum settling velocity of
      bioparticles. In fact, the minimum settling velocity would serve as a major
      selection pressure exerted on bioparticles. It appeared from this study that the
      production of EPS was stimulated significantly by high volume exchange ratio,
      which was associated with marketable accumulation of calcium ion in aerobic
      granulation. It is expected that this study may offer insights into the mechanism
      of aerobic granulation.

PMID- 15970309
TI  - Improvement in electrokinetic remediation of heavy metal spiked kaolin with the
      polarity exchange technique.
AB  - In the electrokinetic treatment of heavy metal polluted soil, an alkaline
      environment is generated at the cathode side. It provokes the precipitation of
      metal ions as hydroxides into the soil and diminishes the capability of the
      electroremediation to clean the polluted site. In this work the "polarity
      exchange" technique is presented as a simple way to avoid the negative effect of
      OH(-) on metal transportation. This technique lies in the operation during short
      time intervals at inverted polarity, so that the generation of H+ ions from the
      oxidation of water neutralize in the alkaline zone where the metal is
      precipitated, favouring its dissolution. Once the metals are redissolved, the
      polarity is set to the original position to transport them to the desired
      direction. Kaolin clay contaminated with Mn was used to test the feasibility of
      the polarity exchange technique. The application of the "conventional technique"
      dealt with a removal of 14% of the initial Mn in 7.6d. For a similar treatment
      time the polarity exchange technique resulted in 72% of removed Mn. Successive
      polarity exchanges will yield with a complete decontamination of the soil with a
      moderate increment in the electric power consumption.

PMID- 15970310
TI  - U-series and ESR analyses of bones and teeth relating to the human burials from
      Skhul.
AB  - In order to resolve long-standing issues surrounding the age of the Skhul early
      modern humans, new analyses have been conducted, including the dating of four
      well-provenanced fossils by ESR and U-series. If the Skhul burials took place
      within a relatively short time span, then the best age estimate lies between 100
      and 135 ka. This result agrees very well with TL ages obtained from burnt flint
      of 119+/-18 ka (Mercier et al., 1993). However, we cannot exclude the possibility
      that the material associated with the Skhul IX burial is older than those of
      Skhul II and Skhul V. These and other recent age estimates suggest that the three
      burial sites, Skhul, Qafzeh and Tabun are broadly contemporaneous, falling within
      the time range of 100 to 130 ka. The presence of early representatives of both
      early modern humans and Neanderthals in the Levant during Marine Isotope Stage 5
      inevitably complicates attempts at segregating these populations by date or
      archaeological association. Nevertheless, it does appear that the oldest known
      symbolic burials are those of early modern humans at Skhul and Qafzeh. This
      supports the view that, despite the associated Middle Palaeolithic technology,
      elements of modern human behaviour were represented at Skhul and Qafzeh prior to
      100 ka.

PMID- 15970311
TI  - First occurrence of early Homo in the Nachukui Formation (West Turkana, Kenya) at
      2.3-2.4 Myr.
AB  - Cognitive abilities and techno-economic behaviours of hominids in the time period
      between 2.6-2.3 Myr have become increasingly well-documented. This time period
      corresponds to the oldest evidence for stone tools at Gona (Kada Gona, West Gona,
      EG 10-12, OGS 6-7), Hadar (AL 666), lower Omo valley (Ftji1, 2 & 5, Omo 57, Omo
      123) in Ethiopia, and West Turkana (Lokalalei sites -LA1 & LA2C-) in Kenya. In
      2002 a new palaeoanthropological site (LA1alpha), 100 meters south of the LA1
      archaeological site, produced a first right lower molar of a juvenile hominid
      (KNM-WT 42718). The relative small size of the crown, its marked MD elongation
      and BL reduction, the relative position of the cusps, the lack of a C6 and the
      mild expression of a protostylid, reinforced by metrical analyses, demonstrate
      the distinctiveness of this tooth compared with Australopithecus afarensis, A.
      anamensis, A. africanus and Paranthropus boisei, and its similarity to early
      Homo. The LA1alpha site lies 2.2 m above the Ekalalei Tuff which is slightly
      younger than Tuff F dated to 2.34+/-0.04 Myr. This juvenile specimen represents
      the oldest occurrence of the genus Homo in West Turkana.

PMID- 15970312
TI  - Foraging behaviour of the slender loris (Loris lydekkerianus lydekkerianus):
      implications for theories of primate origins.
AB  - Members of the Order Primates are characterised by a wide overlap of visual
      fields or optic convergence. It has been proposed that exploitation of either
      insects or angiosperm products in the terminal branches of trees, and the
      corresponding complex, three-dimensional environment associated with these
      foraging strategies, account for visual convergence. Although slender lorises
      (Loris sp.) are the most visually convergent of all the primates, very little is
      known about their feeding ecology. This study, carried out over 10 (1/2) months
      in South India, examines the feeding behaviour of L. lydekkerianus lydekkerianus
      in relation to hypotheses regarding visual predation of insects. Of 1238 feeding
      observations, 96% were of animal prey. Lorises showed an equal and overwhelming
      preference for terminal and middle branch feeding, using the undergrowth and
      trunk rarely. The type of prey caught on terminal branches (Lepidoptera, Odonata,
      Homoptera) differed significantly from those caught on middle branches
      (Hymenoptera, Coleoptera). A two-handed catch accompanied by bipedal postures was
      used almost exclusively on terminal branches where mobile prey was caught,
      whereas the more common capture technique of one-handed grab was used more often
      on sturdy middle branches to obtain slow moving prey. Although prey was detected
      with senses other than vision, vision was the key sense used upon the final
      strike. This study strongly supports the notion that hunting for animal prey was
      a key ecological determinant in selecting for visual convergence early on in
      primate evolution. The extreme specialisations of slender lorises, however,
      suggest that early primates were not dedicated faunivores and lend further
      support to the emerging view that both insects and fruits were probably important
      components of the diet of basal primates, and that exploitation of fruits may
      account for other key primate traits.

PMID- 15970313
TI  - An integrated modelling and multicriteria analysis approach to managing nitrate
      diffuse pollution: 2. A case study for a chalk catchment in England.
AB  - The site-specific land use optimisation methodology, suggested by the authors in
      the first part of this two-part paper, has been applied to the River Kennet
      catchment at Marlborough, Wiltshire, UK, for a case study. The Marlborough
      catchment (143 km(2)) is an agriculture-dominated rural area over a deep chalk
      aquifer that is vulnerable to nitrate pollution from agricultural diffuse
      sources. For evaluation purposes, the catchment was discretised into a network of
      1 kmx1 km grid cells. For each of the arable-land grid cells, seven land use
      alternatives (four arable-land alternatives and three grassland alternatives)
      were evaluated for their environmental and economic potential. For environmental
      evaluation, nitrate leaching rates of land use alternatives were estimated using
      SHETRAN simulations and groundwater pollution potential was evaluated using the
      DRASTIC index. For economic evaluation, economic gross margins were estimated
      using a simple agronomic model based on nitrogen response functions and
      agricultural land classification grades. In order to see whether the site
      specific optimisation is efficient at the catchment scale, land use optimisation
      was carried out for four optimisation schemes (i.e. using four sets of criterion
      weights). Consequently, four land use scenarios were generated and the site
      specifically optimised land use scenario was evaluated as the best compromise
      solution between long term nitrate pollution and agronomy at the catchment scale.

PMID- 15970315
TI  - Anxiolytic-like effect of paeonol in mice.
AB  - The present study in mice compared the putative anxiolytic-like effect of
      paeonol, a phenolic component from the root bark of Paeonia moutan, with the
      benzodiazepine diazepam in the elevated plus maze and the light/dark box-test.
      The comparison was also with regard to locomotor activity (open-field test) and
      myorelaxant potential (inclined plane test). As with 2 mg/kg diazepam, paeonol
      (at 17.5 mg/kg) increased the percentage of time spent on open arms in the
      elevated plus maze and increased the time spent in the light area of the
      light/dark box (at 8.75 and 17.5 mg/kg). Since paeonol, in contrast to diazepam,
      had no effect on either the number of squares entered in the open-field test or
      in the inclined plane test, its side-effect profile is considered as superior to
      the benzodiazepine.

PMID- 15970314
TI  - Serotonergic/glutamatergic interactions: potentiation of phencyclidine-induced
      stimulus control by citalopram.
AB  - Previous investigations in our laboratory have found that the stimulus effects of
      the hallucinogenic serotonergic agonists DOM and LSD are potentiated by
      phencyclidine [PCP], a non-competitive NMDA antagonist. Also suggestive of
      behaviorally significant serotonergic/glutamatergic interactions is our finding
      that stimulus control by both PCP and LSD is partially antagonized by the mGlu2/3
      agonist, LY 379268. These observations coupled with the fact that the stimulus
      effects of LSD and DOM are potentiated by selective serotonin reuptake inhibitors
      [SSRIs] led us in the present investigation to test the hypothesis that stimulus
      control by PCP is potentiated by the SSRI, citalopram. Stimulus control was
      established with PCP [3.0 mg/kg; 30 min pretreatment time] in a group of 12 rats.
      A two-lever, fixed ratio 10, positively reinforced task with saline controls was
      employed. Potentiation by citalopram of an intermediate dose of PCP was observed.
      In an attempt to establish the mechanism by which citalopram might interact with
      PCP, subsequent experiments examined the effects on that interaction of
      antagonists at serotonergic receptors. It was found that the selective 5-HT2C
      selective antagonists, SDZ SER 082 and SB 242084, significantly, albeit only
      partially, blocked the effects of citalopram on PCP. In agreement with our
      previous conclusions regarding the interaction of citalopram with DOM, the
      present data suggest that potentiation of the stimulus effects of PCP by
      citalopram are mediated in part by agonist activity at 5-HT2C receptors.

PMID- 15970316
TI  - Long-term motility and fertility conservation of chilled canine semen using egg
      yolk added Tris-glucose extender: in vitro and in vivo studies.
AB  - The effects of medium exchange on motility parameters of chilled canine semen
      preserved in egg yolk Tris-glucose (EYTG) extender were analyzed over a 27-d
      period. Semen extender was exchanged at three time points (Days 11, 21 and 27)
      after collection, when motility parameters were demonstrated to significantly
      decrease from parameters observed at semen preparation (Day 0) or at day of
      previous extender exchange. In the absence of medium exchanges, motile
      spermatozoa were observed up to Day 16 (mean +/- S.D. 1.5 +/- 0.3% of motile
      spermatozoa). A stimulation of the different semen motility parameters was
      observed after extender exchange. Semen extender exchange at Day 11 allowed
      conservation of motility until Day 21, compared to 16 d in the absence of
      extender exchange. At Day 21, when spermatozoa appeared immobile or dead, a
      second extender exchange was performed, allowing the extension of motility
      conservation up to Day 27. The third extender exchange, performed at Day 27, was
      no longer associated with motility stimulation. Glucose content in the medium
      decreased slowly over time; a concomitant decrease in pH was also observed. No
      changes in osmolarity were observed over time. To verify the fertility of long
      term conserved chilled semen, two groups of 10 bitches were inseminated either
      once (Group 1) or twice at 48-h intervals (Group 2) intra-vaginally with semen
      conserved chilled for a mean of 9 +/- 1.8 d. Out of the 10 bitches inseminated
      once, 5 became pregnant, versus 7 in the group of animals inseminated twice. The
      present study reports the possibility to extend the conservation of chilled
      canine semen up to 3 wk with conservation of good fertility for at least 10 d.
      The role of energetic substrate and pH alteration is postulated and the
      classically accepted relation of semen motility/viability is raised.

PMID- 15970317
TI  - The definition of child maltreatment: from case study to construct.

PMID- 15970318
TI  - Advances in research definitions of child maltreatment.

PMID- 15970319
TI  - The dimensions of maltreatment: introduction.
AB  - This special issue includes an introduction and seven papers exploring dimensions
      of maltreatment including type, severity, chronicity, and substantiation status
      of referrals to CPS, utilizing a subsample of the LONGSCAN studies. Each paper
      examines one of the dimensions of maltreatment from various perspectives to
      determine if different conceptualizations of a dimension, examined in isolation,
      account for different amounts of variation in child outcomes. A final paper
      assesses the relationship of the combined maltreatment dimensions, including
      interactions, on a single sample of maltreated children from the LONGSCAN study.
      This final paper explores the individual contribution of the "best"
      conceptualizations of the maltreatment dimensions in relation to each other, and
      to the 10 child outcomes of interest. Implications of the findings from these
      papers for future research on dimensions of child maltreatment are discussed in
      two independent commentaries.

PMID- 15970320
TI  - Describing maltreatment: do child protective service reports and research
      definitions agree?
AB  - OBJECTIVE: The National Research Council identified inadequate research
      definitions for abuse and neglect as barriers to research in child maltreatment.
      We examine the concordance between child protective services (CPS)
      classifications of maltreatment type with the determinations of type from two
      research coding systems. We contrast the two coding systems and the CPS
      classification, in their ability to predict subsequent difficulties in the
      psychological functioning of maltreated children at age 8. METHOD: The sample
      included 545 children who were enrolled in Longitudinal Studies of Child Abuse
      and Neglect (LONGSCAN) with a report of child maltreatment, had data collected at
      approximately 4 and 8 years of age, and had a lifetime review of CPS records to
      age 8. CPS Maltreatment reports were coded using LONGSCAN's modification of the
      Maltreatment Classification System (MMCS) and the Second National Incidence Study
      maltreatment coding system (NIS-2). The first analyses used reports as the unit
      of analysis to examine agreement between CPS and research determinations of
      allegation type. Validation analyses examined outcomes for each type of
      maltreatment experienced after age 4 under each coding system using the Child
      Behavior Checklist (CBCL), Trauma Symptom Checklist-Alternative form, and the
      Vineland Screener as the measures of outcome. Control variables were the CBCL and
      Battelle Developmental Screener, measured at age 4. RESULTS: There were a total
      of 1980 reports of maltreatment for 545 study children although only 1593 CPS
      reports specified at least one type of maltreatment. There were differences
      between the type of maltreatment recorded in child protective service records and
      the conclusions reached by either research classification system. CPS
      classifications were most discordant with the research systems for emotional
      abuse and neglect. Nearly 10% of physical and sexual abuse reports, as determined
      by the MMCS, were classified as neglect by the child protective service agencies.
      The NIS-2 system and the MMCS had very high Kappa statistics for agreement for
      physical and sexual abuse. The validity of the research definitions for physical
      and sexual abuse was demonstrated in models predicting children's functioning at
      age 8. Prediction of child functioning was significantly but modestly improved in
      several domains compared to the CPS classifications. CONCLUSION: Both research
      classification systems moderately improved on the prediction of the adverse
      effects of maltreatment compared to the characterization of a maltreatment
      exposure as recorded by CPS.

PMID- 15970321
TI  - Defining maltreatment according to substantiation: distinction without a
      difference?
AB  - OBJECTIVE: To examine whether children with substantiated maltreatment reports
      between 4 and 8 years of age differ from children with unsubstantiated reports on
      any of 10 behavioral and developmental outcomes. METHOD: Longitudinal data from
      806 children and their adult caregivers collected in four US study sites were
      pooled and analyzed using Analysis of Variance (ANOVA) and multivariate linear
      regression. RESULTS: There were no significant differences between the mean
      scores of children with unsubstantiated and substantiated maltreatment reports
      filed between 4 and 8 years of age for any of the 10 behavioral and developmental
      outcomes. In the multivariate analysis, substantiation status was not
      significantly associated with any of the 10 outcomes after adjusting for prior
      functioning, prior maltreatment status, and sociodemographic characteristics.
      Findings from within-site analyses were generally consistent with the pooled
      analyses in finding no association between substantiation status and the outcomes
      examined. CONCLUSIONS: In this high-risk sample, the behavioral and developmental
      outcomes of 8-year-old children with unsubstantiated and substantiated
      maltreatment reports filed between ages 4 and 8 were indistinguishable. Future
      research should attempt to replicate these findings on probability samples that
      represent the full range of childhood maltreatment risk and with models that
      control for the impact of social services.

PMID- 15970322
TI  - Defining child neglect based on child protective services data.
AB  - OBJECTIVES: To compare neglect defined by Child Protective Services official
      codes with neglect defined by a review of CPS narrative data, and to examine the
      validity of the different neglect measures using children's functioning at age 8
      years. METHODS: Data are from 740 children participating in a consortium of
      longitudinal studies on child abuse and neglect; 481 had at least one CPS report
      prior to age 8. CPS records were reviewed to ascertain both broad CPS types of
      neglect as well as specific subtypes of neglect using a modified version of the
      Maltreatment Classification System (MMCS). Frequencies of, and correlations
      among, the types and subtypes of neglect were examined. The validity of the
      neglect measures was evaluated by examining their relationships with children's
      functioning at age 8. RESULTS: The CPS neglect types and MMCS subtypes were
      moderately correlated, as were the MMCS subtypes of neglect. In general, neglect
      was only modestly associated with children's functioning at age 8 (r2=1-4%), with
      few differences between the CPS neglect types and the MMCS subtypes. There were
      significant associations with children's total and externalizing behavior
      problems, impaired socialization, and impaired daily living skills. Among the
      specific subtypes, neglect of children's medical needs was related to
      externalizing behavior problems, impaired socialization, and impaired daily
      living skills. Neglect of children's hygiene needs was related to impaired
      socialization. CONCLUSION: The moderate correlations among CPS and MMCS types and
      subtypes of neglect and their similar associations with children's functioning
      suggest that the considerable effort involved in coding neglect subtypes from CPS
      narrative data may yield limited incremental knowledge regarding the types of
      neglect children experience and their sequelae. However, the MMCS does offer
      useful descriptive information on the nature of neglect children experience, and
      may guide future research and practice on optimal ways to conceptualize neglect.

PMID- 15970323
TI  - Do allegations of emotional maltreatment predict developmental outcomes beyond
      that of other forms of maltreatment?
AB  - OBJECTIVES: To understand the features of child abuse/neglect (CA/N) allegations
      in cases with emotional maltreatment (EMT) allegations, as well as the features
      of the EMT allegations themselves, and to describe any associations of EMT with
      distinct impairments of children's behavior, emotion and functioning. METHOD: The
      sample consisted of 806 high-risk children, 545 with one or more maltreatment
      reports to CPS. The Maltreatment Classification System was used to record the
      number and severity levels of maltreatment allegations, which compared cases with
      and without EMT. Multiple regression analyses were conducted using 10 outcome
      scales from the Child Behavior Checklist, Vineland Screener, and Trauma Symptom
      Checklist. Successive blocks of predictor variables included demographics,
      maltreatment classification variables, maternal and family characteristics, and
      study site. RESULTS: When there were allegations of EMT as well as CA/N in a CPS
      case-record (by age 8), the CA/N allegations tended to be either more frequent or
      less severe than those kinds of allegations in cases without EMT. When neglect
      was alleged to occur with EMT, neglect allegations outnumbered allegations of
      EMT. However, when sexual abuse allegations were accompanied by EMT allegations,
      there were more EMT allegations than sexual abuse allegations in the cases.
      Higher severity ratings for EMT allegations than for physical abuse occurred when
      cases included any abuse. Distinctive effects of EMT subtypes were found between
      problems of safety/restriction and self-reported anger symptoms, and between
      problems of self-esteem/autonomy and posttraumatic stress. CONCLUSION:
      Differences exist between the CA/N allegations in cases with and without EMT.
      Having few cases containing only EMT allegations made it difficult to assess
      distinctive harm associated with EMT. Certain types of EMT allegations were
      associated with increases in children's anger and posttraumatic stress.

PMID- 15970324
TI  - What's in a name? A comparison of methods for classifying predominant type of
      maltreatment.
AB  - OBJECTIVE: The primary aim of the study was to identify a classification scheme,
      for determining the predominant type of maltreatment in a child's history that
      best predicts differences in developmental outcomes. METHOD: Three different
      predominant type classification schemes were examined in a sample of 519 children
      with a history of alleged maltreatment. Cases were classified into predominant
      maltreatment types according to three different schemes: Hierarchical regression
      analyses examined whether the HT, SFT, and EHT type classifications contributed
      to prediction of child behavior problems, trauma symptoms and adaptive
      functioning. RESULTS: After controlling for demographic factors, the HT
      definitions predicted four outcomes, while the SFT definitions predicted three,
      and the EHT classifications contributed to the prediction of five child outcomes.
      The co-occurrence of multiple types of maltreatment was robustly related to
      outcomes. However, the HT and SFT classifications predicted outcomes even after
      accounting for the co-occurrence of multiple maltreatment subtypes. CONCLUSION: A
      classification scheme that differentiates between type combinations and single
      maltreatment types may have the greatest predictive validity. Over and above
      knowing about co-occurrence of maltreatment sub-types, it is important to
      understand what type, or constellation of types, of maltreatment have been
      alleged in a child's history.

PMID- 15970325
TI  - Measuring the severity of child maltreatment.
AB  - OBJECTIVE: The purpose was to identify different operational definitions of
      maltreatment severity, and then to examine their predictive validity. METHOD:
      Children and their primary caregivers participating in a consortium of ongoing
      longitudinal studies were interviewed when they were approximately 4 and 8 years
      of age to assess behavior problems, and developmental and psychological
      functioning. Four different severity definitions were identified and applied to
      519 children who were reported for alleged maltreatment between Birth and the Age
      8 interview. A taxonomy for defining maltreatment characteristics (Barnett,
      Manly, & Cicchetti, 1993) was applied to Child Protective Service records to
      define severity as (a) Maximum Severity within each of five maltreatment types,
      (b) Overall Maximum Severity across the five types, (c) Total Severity or the sum
      of the maximum severity for each of five types, and (d) Mean Severity or the
      average severity for those types of maltreatment alleged, during each of two time
      periods-Birth to Age 4, and Age 4 to Age 8. RESULTS: Regression analyses that
      controlled for socio-demographic factors, early maltreatment (Birth to Age 4),
      prior functioning (Age 4), and site revealed that (a) all four severity
      definitions for maltreatment reports between Age 4 and Age 8 predicted Age 8
      behavior problems, (b) Maximum Severity by Type and Mean Severity predicted
      adaptive functioning at Age 8, and (c) only Maximum Severity by Type was related
      to anger, at Age 8. Follow-up regression analyses indicated that only Maximum
      Severity by Type, specifically physical abuse, accounted for outcomes, beyond
      maltreatment occurrence versus non-occurrence. CONCLUSION: The results suggest
      that maltreatment severity definitions that preserve ratings within types of
      maltreatment may be the optimal approach to measure the severity of children's
      experiences.

PMID- 15970326
TI  - Defining maltreatment chronicity: are there differences in child outcomes?
AB  - OBJECTIVE: For nearly 25 years researchers have suggested that better taxonomic
      systems conceptualizing and reliably differentiating among different dimensions
      of maltreatment are required. This study examines the utility of three different
      characterizations of one dimension of maltreatment, chronicity, to predict child
      behavioral and emotional functioning in a sample of maltreated children. A
      secondary objective of the study is to examine additional parameters of
      maltreatment inherent in our definitions of chronicity: age at first report to
      CPS, extent and continuity of maltreatment. METHOD: The study consists of
      children reported for maltreatment (N=519) from the larger LONGSCAN study cohort.
      Lifetime maltreatment data were collected from CPS records and coded into two
      chronicity constructs: "developmental" and "calendar" definitions. Variables for
      age at first report, frequency, extent and continuity of maltreatment reports
      also were constructed. Hierarchical regression analyses were utilized to
      determine the extent to which the various chronicity constructs contributed to
      the prediction of child outcomes. RESULTS: The most salient definition of
      chronicity, in terms of its effects on child behavioral and emotional
      functioning, varied by outcome. The developmental definition was found to have
      the most balanced sensitivity across outcomes. Among other significant findings,
      extent and continuity of maltreatment contributed respectively to the prediction
      of behavior and emotional trauma symptoms. Early age at first report was a
      predictor of poor daily living skills. CONCLUSION: Chronicity is a complex
      construct. Findings indicate there are multiple parameters that make up the
      chronicity construct itself that may be important for understanding child
      outcomes.

PMID- 15970327
TI  - Maltreatment's wake: the relationship of maltreatment dimensions to child
      outcomes.
AB  - OBJECTIVE: The aim of this exploratory study was to examine the extent to which,
      in combination, the best constructions of basic dimensions of maltreatment,
      identified in other papers from LONGSCAN, predict child outcomes. METHOD:
      Maltreatment records of a sample of 203 children were used to define dimensions
      of maltreatment related to Type, Severity, Chronicity, and Age at First Report.
      The definitions were based upon findings presented in other papers in this
      special issue. Children's behavioral and emotional functioning was examined at
      age 8 using standardized measures of problem behaviors, socialization and
      adaptation, and trauma symptomatology. Backward elimination regression was used
      to screen for interactions among the dimensions; regression models including
      dimensions and significant interactions were then run for each child outcome.
      Stratified partial correlations were utilized to explicate significant
      interactions. RESULTS: Individual maltreatment dimensions were found to have
      distinct effects on child functioning. Additionally, dimensions of maltreatment
      were interrelated and interacted in determining outcomes. Type of maltreatment
      (as indicated by the maximum severity rating of each type) was the most
      consistent predictor across outcomes, albeit different types predicted different
      outcomes. Various dimensional interactions were significant predictors of
      different outcomes. CONCLUSION: The results suggest that a comprehensive
      assessment of a child's maltreatment experience, including type and severity,
      when the maltreatment began and the pattern of maltreatment across the life span,
      is important to understanding the effects of maltreatment on children's growth
      and development.

PMID- 15970328
TI  - The plasmid pBMBt1 from Bacillus thuringiensis subsp. darmstadiensis (INTA Mo14
      4) replicates by the rolling-circle mechanism and encodes a novel insecticidal
      crystal protein-like gene.
AB  - This work describes a novel rolling-circle replicating (RCR) plasmid pBMBt1 from
      Bacillus thuringiensis subsp. darmstadiensis (INTA Mo14-4) encoding an
      insecticidal crystal protein-like gene. pBMBt1 (6700 bp) contains three ORFs and
      their putative transcription initiation sites and Shine-Dalgarno sequences were
      localized. ORF1 encodes a 34.6 kDa protein which showed identity with the protein
      CryC53 from B. thuringiensis subsp. cameroun (24.6%), the Cry15Aa insecticidal
      crystal protein from B. thuringiensis subsp. thompsoni (21.9%) and the Mtx3
      protein from Bacillus sphaericus (27.8%). The ORF2 (52.3 kDa) showed a 74%
      identity with the Mob protein coded by pUIBI-1 from B. thuringiensis subsp.
      entomocidus and 64% identity with the Mob protein of pBMY1 from Bacillus
      mycoides; both Mob proteins belong to the pMV158 superfamily. To evaluate the Mob
      protein, the plasmid pHTMob14-4 was constructed. This plasmid shows transfer
      frequencies of 9.1x10(-6) in B. thuringiensis subsp. israelensis (4Q7Gm(R)). The
      ORF3 (23.6 kDa) gene product is homologous to the Rep protein from the plasmid
      pBMYdx of B. mycoides (37.6%). A putative double-strand origin with significant
      homology to that of B. thuringiensis plasmids, and an ssoA-type single-strand
      origin were also identified. Detection of single-stranded pBMBt1 DNA replicating
      intermediaries suggests that replication occurs via the rolling-circle mechanism.

PMID- 15970329
TI  - Perinatal and lifetime exposure to methylmercury in the mouse: behavioral
      effects.
AB  - This project was undertaken to more completely understand the consequences of
      lifetime exposure to methylmercury. A series of experiments examined how
      perinatal or lifetime exposure to methylmercury affected behavioral performances
      in the adult mouse at different ages. One hundred female B6C3F1/HSD mice were
      assigned to one of three dose groups, 0 ppm, 1 ppm, or 3 ppm methylmercury
      chloride administered in a 5 nM sodium carbonate drinking solution. Four weeks
      after initiating dosing, the females were bred with male CBA/J HSD mice to
      produce the trihybrid offspring B6C3F1/HSD x CBA/J HSD. The methylmercury-treated
      litters were split into two subgroups, one exposed throughout its lifetime to the
      original dose, the other exposed through postnatal day 13. Altogether, then, five
      groups were studied: Control, 1 ppm perinatal, 1 ppm lifetime, 3 ppm perinatal,
      and 3 ppm lifetime. Three neurobehavioral indices were evaluated: (1) delayed
      spatial alternation (a test of memory) and (2) running in a wheel to earn food
      pellets (schedule-controlled operant behavior) were assessed starting at 5 and 15
      months of age; (3) hindlimb splay, a measure of motor function, was assessed at
      5, 15, and 26 months of age. Subjects tested at one age were littermates of those
      tested at the other ages. MeHg altered the hindlimb splay distance; control mice
      differed from methylmercury-exposed mice, the 1 ppm lifetime and 3 ppm lifetime
      groups differed from each other, and the analysis yielded an age by dose
      interaction. MeHg exposure altered different measures of wheel running under the
      3 ppm lifetime condition. In the delayed alternation procedure, the mouse was
      required to respond to one of two locations in a strictly alternating sequence.
      More mice from the treated groups, except for the 1 ppm perinatal group, failed
      to meet the criterion at longer delay values. Overall, the results show that
      exposure to low levels of methylmercury produces behavioral effects that depend
      on the test procedure, the dose, the duration of exposure, and the age. Lifetime
      evaluations of exposure to toxicants, beginning with early development, should be
      a component of the risk assessment process for neurotoxicity.

PMID- 15970330
TI  - Using animal models to develop therapeutics for Tourette Syndrome.
AB  - The science of Tourette Syndrome (TS) is advancing at multiple levels of analysis
      and will be enhanced through the use of animal models. Particular challenges in
      the development of TS animal models reflect complex features of this disorder,
      including its waxing and waning course and its "invisible" sensory and psychic
      symptoms. Animal models can achieve face, predictive, or construct validity based
      on their particular features. Predictive validity, of most direct relevance to
      drug development for TS, is achieved to some degree by a several animal models,
      although the reliance of most of these models on measures of motor suppression
      may ultimately limit their utility. Other models achieve construct validity with
      proposed pathophysiological mechanisms related to the immune and neural circuit
      etiologies of TS. One model-deficient sensorimotor gating of the startle reflex
      is discussed in terms of its present and future applications towards advancing
      our understanding of the pathophysiology and treatment of TS. In addition to
      models that will advance the pharmacotherapy of TS, other animal models may
      enhance the utility of nonpharmacologic TS treatments, ranging from behavior
      therapy to deep brain stimulation (DBS).

PMID- 15970331
TI  - A novel device for delivering two-site vibrotactile stimuli to the skin.
AB  - Current methods for applying two-site vibration stimuli to the skin typically
      involve the use of two separate vibrotactile stimulators, which can lead to
      difficulty with positioning of stimuli and in ensuring that stimuli are delivered
      perfectly in phase at the same amplitude and frequency. This report describes the
      Two-Point Stimulator (TPS) that was developed in order to deliver two-point
      stimuli to the skin at variable distances between the sites of stimulation on a
      trial-by-trial basis. The apparatus attaches to a vibrotactile stimulator,
      modifying it from the standard single probe tip to two probe tips. Each of the
      two probe tips can be independently positioned to set the tip-to-tip spacing.
      Both points of the TPS are driven by the single vibrotactile stimulator and
      distances between the two sites can be varied on a trial-by-trial basis. To test
      the device, a modified Bekesy tracking method was developed and used for two
      point limen testing under stimulus conditions of varying amplitude and frequency.
      Data collected were consistent with previously published reports, suggesting that
      one possible use of the device would be to provide a means for improved measures
      of spatio-tactile acuity.

PMID- 15970332
TI  - A new method of selecting Schwann cells from adult mouse sciatic nerve.
AB  - We describe a method of using laminin for the selection and purification of
      Schwann cells in vitro. We also studied the viability of the selected cells
      suspended in alginate beads both in vitro and in vivo. We observed that the
      homogeneity of the Schwann cell culture increased with each round of laminin
      selection and reached 85-90% after five passages. The viability of cells after
      incubation within an alginate bead in vivo was between 73 and 76% compared with
      greater than 90% viability for cells that were maintained in monolayer culture.
      This new method of serial selection using laminin-coated surfaces has optimized
      the purification of a Schwann cell culture expanded from cells harvested from the
      adult sciatic nerve of a mouse. This method has the advantage of being
      technically easier than other methods described and results in a Schwann cell
      culture that is 80-90% homogenous.

PMID- 15970333
TI  - DATA-MEAns: an open source tool for the classification and management of neural
      ensemble recordings.
AB  - The number of laboratories using techniques that allow to acquire simultaneous
      recordings of as many units as possible is considerably increasing. However, the
      development of tools used to analyse this multi-neuronal activity is generally
      lagging behind the development of the tools used to acquire these data. Moreover,
      the data exchange between research groups using different multielectrode
      acquisition systems is hindered by commercial constraints such as exclusive file
      structures, high priced licenses and hard policies on intellectual rights. This
      paper presents a free open-source software for the classification and management
      of neural ensemble data. The main goal is to provide a graphical user interface
      that links the experimental data to a basic set of routines for analysis,
      visualization and classification in a consistent framework. To facilitate the
      adaptation and extension as well as the addition of new routines, tools and
      algorithms for data analysis, the source code and documentation are freely
      available.

PMID- 15970334
TI  - Neuronal development and migration in zebrafish hindbrain explants.
AB  - The zebrafish embryo is an excellent system for studying dynamic processes such
      as cell migration during vertebrate development. Dynamic analysis of neuronal
      migration in the zebrafish hindbrain has been hampered by morphogenetic movements
      in vivo, and by the impermeability of embryos. We have applied a recently
      reported technique of embryo explant culture to the analysis of neuronal
      development and migration in the zebrafish hindbrain. We show that hindbrain
      explants prepared at the somitogenesis stage undergo normal morphogenesis for at
      least 14 h in culture. Importantly, several aspects of hindbrain development such
      as patterning, neurogenesis, axon guidance, and neuronal migration are largely
      unaffected, inspite of increased cell death in explanted tissue. These results
      suggest that hindbrain explant culture can be employed effectively in zebrafish
      to analyze neuronal migration and other dynamic processes using pharmacological
      and imaging techniques.

PMID- 15970335
TI  - The bovine innate immune response during experimentally-induced Pseudomonas
      aeruginosa mastitis.
AB  - Almost half of all clinical cases of mastitis are caused by Gram-negative
      bacteria. Among these bacteria, intramammary infection by Pseudomonas aeruginosa
      remains one of the most refractory to antibiotic therapy. The ability to
      recognize potentially harmful pathogens whether previously encountered or not, as
      well as the induction of an initial pro-inflammatory response to these pathogens,
      are critical components of host innate immunity. Although the innate immune
      response to another Gram-negative mastitis-causing pathogen, Escherichia coli,
      has been well-characterized, little is known about the response to other Gram
      negative bacteria, including P. aeruginosa. The objective of the current study
      was to characterize the systemic and localized bovine innate immune response to
      intramammary infection with P. aeruginosa. The contralateral quarters of ten mid
      lactating Holstein cows were challenged with either saline or P. aeruginosa.
      Following the establishment of infection, milk samples were collected and assayed
      for changes in cytokine and growth factor concentrations, complement activation,
      and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide (LPS)
      binding protein (LBP), two accessory molecules involved in host recognition of
      Gram-negative bacteria. Initial increases in milk somatic cell counts were
      evident within 12h of experimental challenge and remained elevated for >or=3
      weeks. Increased permeability of the mammary gland vasculature, as evidenced by
      elevated milk levels of BSA, was initially observed 20 h post-infection and
      persisted for 2 weeks. Within 32 h of challenge, increased levels of IL-8, TNF
      alpha, IL-10, and IL-12 were detected, however, the elevated levels of these
      cytokines were not sustained for longer than a 24h period. In contrast,
      elevations in IL-1beta, IFN-gamma, TGF-alpha, TGF-beta1, TGF-beta2, sCD14, LBP,
      and activated complement factor 5 (C5a) were sustained for periods of >48 h.
      Systemic changes were characterized by elevated body temperature, induction of
      the acute phase protein synthesis of serum amyloid A and LBP, and a transient
      decrease in circulating neutrophils and lymphocytes. Together, these data
      demonstrate the capability of the mammary gland to mount a robust innate immune
      response to P. aeruginosa that is characterized by the induction of pro
      inflammatory cytokines, complement activation, and increased levels of accessory
      molecules involved in Gram-negative bacterial recognition.

PMID- 15970336
TI  - Development of a reliable assay protocol for identification of diseases (RAPID)
      bioactive amplification with probing (BAP) for detection of bovine ephemeral
      fever virus.
AB  - A rapid, sensitive, and specific assay, RAPID-BAP assay, was developed to detect
      and quantify the G protein-encoding gene of bovine ephemeral fever virus (BEFV).
      This new technique uses a nested PCR and magnetic bead-based DNA probing assay.
      The optimal conditions for the assay were examined. By applying a nested PCR, a
      minimum of 1 copy/mul of the BEFV plasmid DNA could be detected by the assay. The
      optimal hybridization conditions at 50 degrees C in 5x SSC and 0.5% SDS with a 20
      min incubation allowed clear discrimination between negative and positive
      controls. The assay was also highly specific as all negative controls failed to
      show any positive detection. The diagnostic sensitivity of the RAPID-BAP assay,
      real-time RT-PCR, and conventional RT-PCR in the detection of 34 clinical blood
      samples suspected to have BEFV infections were 72.73, 36.36, and 18.18%,
      respectively. The results indicated that the RAPID-BAP assay developed in this
      study was more sensitive than the conventional RT-PCR and real-time RT-PCR assays
      for the detection of BEFV. The novel RAPID-BAP assay is an excellent diagnostic
      tool with high sensitivity, specificity, and fast turnaround time.

PMID- 15970337
TI  - Post-saccadic updating of visual space in the posterior parietal cortex in
      humans.
AB  - Updating of visual space takes place in the posterior parietal cortex to
      guarantee spatial constancy across eye movements. However, the timing of updating
      with respect to saccadic eye movements remains a matter of debate. In the present
      study, event-related potentials (ERPs) were recorded in 15 volunteers during a
      saccadic double-step task to elucidate the time course of the updating process.
      In the experimental condition updating of visual space was required, because both
      saccade targets had already disappeared before the first saccade was executed. A
      similar task without updating requirements served as control condition. ERP
      analysis revealed a significantly larger slow positive wave in the retino-spatial
      dissonance condition compared to the control condition, starting between 150 and
      200 ms after first saccade onset. Source analysis showed an asymmetry with
      respect to the direction of the first saccade. Whereas the source was restricted
      to the right PPC in trials with leftward first saccades, left and right PPC were
      involved in rightward trials. The results of the present study suggest that
      updating of visual space in a saccadic double-step task occurs not earlier than
      150 ms after the onset of the first saccade. We conclude that extraretinal
      information about the first saccade is integrated with motor information about
      the second saccade in the inter-saccade interval.

PMID- 15970338
TI  - The apj receptor is expressed in pancreatic islets and its ligand, apelin,
      inhibits insulin secretion in mice.
AB  - Apelin is the endogenous ligand of the G-protein coupled apj receptor. Apelin is
      expressed in the brain, the hypothalamus and the stomach and was recently shown
      also to be an adipokine secreted from the adipocytes. Although apelin has been
      suggested to be involved in the regulation of food intake, it is not known
      whether the peptide affects islet function and glucose homeostasis. We show here
      that the apj receptor is expressed in pancreatic islets and that intravenous
      administration of full-length apelin-36 (2 nmol/kg) inhibits the rapid insulin
      response to intravenous glucose (1 g/kg) by 35% in C57BL/6J mice. Thus, the acute
      (1-5 min) insulin response to intravenous glucose was 682+/-23 pmol/l after
      glucose alone (n=17) and 445+/-58 pmol/l after glucose plus apelin-36 (n=18;
      P=0.017). This was associated with impaired glucose elimination (the 5-20 min
      glucose elimination was 2.9+/-0.1%/min after glucose alone versus 2.3+/-0.2%/min
      after glucose plus apelin-36, P=0.008). Apelin (2 nmol/kg) also inhibited the
      insulin response to intravenous glucose in obese insulin resistant high-fat fed
      C57BL/6J mice (P=0.041). After 60 min incubation of isolated islets from normal
      mice, insulin secretion in the presence of 16.7 mmol/l glucose was inhibited by
      apelin-36 at 1 mumol/l, whereas apelin-36 did not significantly affect insulin
      secretion at 2.8 or 8.3 mmol/l glucose or after stimulation of insulin secretion
      by KCl. Islet glucose oxidation at 16.7 mmol/l was not affected by apelin-36. We
      conclude that the apj receptor is expressed in pancreatic islets and that apelin
      36 inhibits glucose-stimulated insulin secretion both in vivo and in vitro. This
      may suggest that the islet beta-cells are targets for apelin-36.

PMID- 15970339
TI  - Apelin, orexin-A and leptin plasma levels in morbid obesity and effect of gastric
      banding.
AB  - Maintenance of human energy homeostasis is regulated by a complex network.
      Peptides secreted from the gastrointestinal tract (GI) are signaling to the brain
      and other organs initiating or terminating food intake and energy expenditure. In
      the present study we investigated basal plasma levels of apelin, orexin-A, and
      leptin in morbid obese patients. In addition, we measured in a subgroup of these
      patients in the same individual orexin-A and leptin plasma levels one year after
      gastric banding surgery. METHODS: Basal plasma values were determined in obese
      patients (BMI=48+/-1 kg/m2n=32) after an overnight fast and compared to healthy,
      normal weighted (BMI=22+/-2 kg/m2n=12) controls. In addition, blood samples were
      collected in a subgroup of patients (BMI=48+/-1 kg/m2n=8) the day before surgery
      and 1 year after the operation. Apelin, orexin-A, and leptin levels were analysed
      using ELISAs. RESULTS: One year after the operation obese patients significantly
      lost weight (from 48+/-2 kg/m2 to 39+/-2 kg/m2; p<0,001). Apelin, orexin-A and
      leptin levels in obese patients were significantly higher compared to control
      individuals (736+/-50 pg/ml vs. 174+/-14 pg/ml, p<0.0001; 75.3+/-24.1 pg/ml vs.
      0.8+/-0.4 pg/ml, p<0.0001; 79.0+/-2.4 ng/ml vs. 5.8+/-0.8 ng/ml, p<0.0001,
      respectively). Apelin and leptin plasma concentrations also correlated
      significantly with BMI (r=0.769, p<0.0001; r=0.778; p<0.0001, respectively),
      while orexin-A correlation was rather weak (r=0.335, p<0.03). No difference
      between pre- and post-operative orexin-A levels was observed, while leptin plasma
      levels significantly decreased from 45.1+/-5.4 ng/ml to 27.3+/-6.0 ng/ml
      (p=0.015). CONCLUSIONS: Apelin, orexin-A, and leptin plasma levels correlated
      positively with the BMI. One year after gastric banding with significant loss in
      BMI basal plasma levels of leptin decreased, while orexin-A remained unchanged.

PMID- 15970340
TI  - Carotid intima-medial thickness as a marker of disease activity in Takayasu's
      arteritis.
AB  - BACKGROUND: Assessment of disease activity in patients with Takayasu's arteritis
      (TA) is difficult due to absence of definitive tests. Presence of carotid intima
      medial thickening has been suggested as a possible marker of inflammation and
      disease activity. METHODS: We evaluated common carotid artery carotid intima
      medial thickness (CCA-IMT) in 56 common carotid arteries (CCAs) in 28 healthy
      controls and 74 CCAs in 37 patients of TA. We correlated these findings with the
      presence of activity as assessed by the National Institutes of Health (NIH)
      criteria. RESULTS: CCA-IMT was increased (>0.8 mm) in 59% of the patients with
      TA. In patients with disease activity, the CCA-IMT was more than in those without
      activity (1.5+/-0.16 vs. 0.9+/-0.2 mm, P<0.005). This is presumably because of
      ongoing inflammation causing abnormal thickening. Even among patients without
      active disease, CCA-IMT was more than in controls (0.9+/-0.2 vs. 0.6+/-0.1 mm,
      P<0.05) possibly due to a milder degree of inflammation or healing with fibrosis.
      All patients with angiographic carotid obstruction had increased CCA-IMT
      irrespective of whether they were active or not. However, in patients with
      angiographically normal carotid arteries, CCA-IMT was increased only among the
      patients who were active (1.4+/-0.2 vs. 0.7+/-0.04, P<0.05). Abnormal CCA-IMT as
      marker of disease activity had a sensitivity of 82% and specificity of 60%. On
      excluding patients with increased CCA-IMT who had angiographic carotid stenosis
      (because the increase in CCA-IMT cannot be attributed entirely to activity alone
      in these patients), the specificity increased to 70%. CONCLUSION: Increased CCA
      IMT is a reliable marker of active disease, especially in the absence of
      angiographically visible carotid disease.

PMID- 15970341
TI  - Effect of beta-blockers on the mortality of Japanese patients with myocardial
      infarction.
AB  - BACKGROUND: After a myocardial infarction, a higher prevalence of coronary
      vasospastic response has been reported in the Japanese population than in the
      Caucasian population. Beta-blockers may exacerbate coronary vasospasm. However,
      beta-blockers are given to Japanese patients after an acute myocardial
      infarction, though the mortality benefit is unknown. Thus, we investigated the
      mortality benefit of beta-blockers given to Japanese patients after an acute
      myocardial infarction. METHODS: We prospectively studied consecutive patients
      with a first myocardial infarction admitted to the coronary care unit of Kansai
      Medical University Hospital, Osaka, Japan from May 1994 through the end of 2001.
      Patients who died during hospitalization or who were referred for coronary artery
      bypass graft surgery were excluded. The association of beta-blocker use with
      mortality after discharge was assessed by a proportional hazards regression
      analysis. RESULTS: There were 546 patients and 400 (73.3%) patients were treated
      with beta-blockers at the time of discharge from hospital. During a mean follow
      up of 2 years, 46 (8.4%) patients died. Beta-blocker therapy was associated with
      a reduced mortality after adjustment for age, gender, Q wave myocardial
      infarction, reperfusion therapy during acute phase, Killip functional class,
      serum creatinine level, cardiovascular risk factors, and medications (hazard
      ratio=0.51, 95% confidence interval=0.27 to 0.95). CONCLUSIONS: Contrary to the
      concern that beta-blocker therapy might induce coronary vasospasm and reduce
      survival, beta-blocker therapy improved survival after discharge in Japanese
      patients with a first myocardial infarction.

PMID- 15970342
TI  - Intra-coronary high-dose CD34+ stem cells in patients with chronic ischemic heart
      disease: a 12-month follow-up.
AB  - Current stem cell protocols for ischemic heart disease are limited by the small
      numbers of cells that can be obtained by bone marrow aspirate. To increase
      myocardial delivery of bone marrow stem cells in patients with chronic ischemic
      heart disease (CIHD), we used granulocyte colony stimulating factor (G-CSF) for
      bone marrow mobilization of CD34+ cells, enabling intracoronary infusion of large
      numbers of CD34+ stem cells. Patients with CIHD (n = 5) demonstrated
      significantly reduced numbers of CD34+ cells mobilized by G-CSF in comparison to
      age-matched controls. Sustained reduction in anginal symptoms and improvement in
      quality of life scores was seen in all patients following infusion of cells.
      Moreover, mean collateral flow grade at 12-month follow-up angiography
      significantly improved, indicating sustained myocardial neovascularization. No
      proliferative retinopathy was induced and no in-stent restenosis seen. However,
      in two patients with documented increase in collateral flow, complications arose,
      one developing an acute coronary syndrome and the other a lentigo maligna. These
      results demonstrate the feasibility of G-CSF mobilization, leukapheresis and
      intracoronary transfer of CD34+ stem cells in patients with CIHD, but longer-term
      studies are required to ensure that this protocol is safe and effective.

PMID- 15970345
TI  - Development of a micro-plate magnetic chemiluminescence enzyme immunoassay
      (MMCLEIA) for rapid- and high-throughput analysis of 17beta-estradiol in water
      samples.
AB  - A novel method of micro-plate magnetic chemiluminescence enzyme immunoassay
      (MMCLEIA) for the screening of 17beta-estradiol in water samples was proposed. It
      used the micro-plate magnetic separator designed by ourselves which can achieve
      the high-throughput analysis without the samples pre-treatment and the sensitive
      chemiluminescence system of AMPPD-ALP system. The method showed specific
      recognition of estrogen, without cross-reactions for three other major estrogenic
      compounds (17beta-estradiol (E2), estriol (E3), ethinyl (E2)) commonly found in
      water. The MMCLEIA was also especially suitable for the large-scale samples
      processing. The working range for 17beta-estradiol was 10-3000 pg/ml. The assay
      sensitivity was 5.4 pg/ml. Both intra- and inter-assay had relative standard
      deviation of less 15%. The effect of several physico-chemical parameters, such as
      the ratio of antibody versus antigen, incubation time and the concentration of
      detergent were studied. This method has been successfully applied to the
      preliminary detection of the sea-water. Compared with the chemiluminescence
      enzyme-linked immunosorbed assay, the correlation was good.

PMID- 15970344
TI  - Attentional training in elderly subjects affects voluntarily oriented, but not
      automatic attention: a neurophysiological study.
AB  - OBJECTIVES: Our study aimed at investigating the effect of repetitive recordings
      on somatosensory evoked potentials (SEPs) related to spatial attention in a
      population of healthy elderly subjects. METHODS: Fifteen healthy elderly subjects
      were tested for six consecutive days using a somatosensory oddball paradigm, in
      which target stimuli were applied above the elbow and the non-target stimuli on
      the ipsilateral shoulder. Brain electrical activity was recorded from six scalp
      electrodes (Fz, Cz, F3, F4, T3 and T4). RESULTS: The N140 response to target
      stimuli showed a significantly decreased amplitude across the sessions with the
      lowest value during the fourth day of recording and with a partial recovery at
      the sixth day. On the contrary, the amplitude of the N140 response to non-target
      stimuli and that of the P300 potential to target stimuli were not significantly
      modified. CONCLUSIONS: The significant amplitude reduction of the N140 potential
      in target, but not in non-target recordings across sessions, suggests that the
      voluntarily oriented attention is reduced by stimulus repetition, while the
      automatic attention is not.

PMID- 15970346
TI  - Synonymous codon usage bias in 16 Staphylococcus aureus phages: implication in
      phage therapy.
AB  - To reveal the factors influencing architecture of protein-coding genes in
      staphylococcal phages, relative synonymous codon usage variation has been
      investigated in 920 protein-coding genes of 16 staphylococcal phages. As expected
      for AT rich genomes, there are predominantly A and T ending codons in all 16
      phages. Both Nc plot and correspondence analysis on relative synonymous codon
      usage indicates that mutation bias influences codon usage variation in the 16
      phages. Correspondence analysis also suggests that translational selection and
      gene length also influence the codon usage variation in the phages to some extent
      and codon usage in staphylococcal phages is phage-specific but not S. aureus
      specific. Further analysis indicates that among 16 staphylococcal phages, 44AHJD,
      P68 and K may be extremely virulent in nature as most of their genes have high
      translation efficiency. If this is true, then above three phages may be useful
      for curing staphylococcal infections.

PMID- 15970347
TI  - Salmonella-like bioadhesive nanoparticles.
AB  - The aim of this work was to evaluate the bioadhesive potential of a polymeric
      vector obtained by the association between Gantrez AN nanoparticles and flagella
      enriched Salmonella enteritidis extract. Fluorescently labelled nanoparticles (SE
      NP) were prepared, after incubation between the polymer and the extract, by a
      solvent displacement method and cross-linkage with 1,3-diaminopropane. SE-NP
      displayed a size close to 280 nm and the amount of associated bacterial extract
      was 18 mug/mg nanoparticle. Flagellin represents more than 80% of the total
      proteins associated with SE-NP, which was identified by SDS-PAGE and confirmed by
      Western blotting. Concerning the bioadhesive properties, SE-NP shows an important
      tropism for the ileum. In fact, about 50% of the given dose of SE-NP was found in
      this gut region for at least 3 h. Interestingly, the bioadhesive ability of SE-NP
      correlated well with the described colonisation profile for Salmonella
      enteritidis. This fact was corroborated by competitive tissue distribution
      studies. Thus, when SE-NP and Salmonella cells were administered together by the
      oral route, both the bacteria and the nanoparticles displayed a similar
      distribution within the intestinal mucosa. However, the ability of SE-NP to be
      taken up by Peyer's patches appeared to be negatively affected by the presence of
      the bacteria. Similarly, when SE-NP was administered 30 min before cells, SE-NP
      were found broadly distributed in Peyer's patches, whereas the bacteria were
      neither able to adhere to nor penetrate this lymphoid tissue. In summary, SE-NP
      demonstrated their Salmonella-like gut colonization, which can be a useful vector
      for oral targeting strategies.

PMID- 15970349
TI  - Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co
      glycolic acid) microspheres.
AB  - In recent years, the acylation of peptides during the erosion of poly(lactic
      acid) and poly(lactic-co-glycolic acid) microspheres has been described in the
      literature. To investigate whether insulin is prone to the covalent attachment of
      lactic or glycolic acid, insulin-loaded PLA and PLGA microspheres containing 5%
      bovine insulin were manufactured using a w/o/w multiple emulsion-solvent
      evaporation technique. Microspheres were characterized for their insulin
      encapsulation efficiency and release characteristics in phosphate-buffered saline
      (PBS) at pH 7.4 and 37 degrees C. Moreover, the stability of the peptide during
      18 days of release was evaluated using HPLC and HPLC-MS techniques. The results
      showed that the insulin loading efficiencies of PLA and PLGA microspheres were
      75.18% and 79.63%, respectively. The microspheres were spherical with relatively
      porous surfaces with an average diameter of 40 and 53 mum, respectively. Insulin
      release from the microspheres was characterized by an initial burst, which was
      attributed to the amount of protein located on or close to the microsphere
      surface. The total ion chromatogram (TIC) of insulin samples extracted after 18
      days of erosion in phosphate buffer pH 7.4 at 37 degrees C revealed that
      deamidation was the major mechanism of instability. Surprisingly, no acylation
      products were found. Control experiments in concentrated lactic acid solutions
      confirmed a minimal reactivity of the peptide under these conditions.

PMID- 15970348
TI  - Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis.
AB  - Vascular endothelial growth factor (VEGF), a potent angiogenic molecule specific
      for vascular endothelial cells, is overexpressed in most tumors and closely
      associated with tumor growth and metastasis. It has been shown that a soluble
      fragment of VEGF receptor Flt-1 (sFlt-1) has anti-angiogenic properties by way of
      its antagonist activity against VEGF. In the present study, we demonstrated that
      the stable expression of sFlt-1 by endothelial cell targeted non-viral gene
      delivery inhibited the angiogenesis of endothelial cells. A targeted polymeric
      gene delivery system, PEI-g-PEG-RGD, was developed by incorporating the
      alphanubeta3/alphanubeta5 integrin-binding RGD peptide, ACDCRGDCFC (single-letter
      amino acid code), into the cationic polymer, polyethylenimine (PEI) via a
      hydrophilic polyethylene glycol (PEG) spacer. The functional analysis of
      therapeutic gene encoding sFlt-1/carrier complex was performed with an
      endothelial cell proliferation assay. The complex of sFlt-1 gene with PEI-g-PEG
      RGD conjugate efficiently inhibited the proliferation of cultured endothelial
      cells, representing that expressed sFlt-1 predominantly bound to exogenous VEGF
      and blocked the binding of VEGF to the full-length Flt-1 receptor. These findings
      suggest that the combination of targeted gene carrier and sFlt-1 possesses the
      potential to be an efficient tool for the anti-angiogenic gene therapy to treat
      cancer.

PMID- 15970350
TI  - The risk of adefovir monotherapy in human immunodeficiency virus (HIV) and
      hepatitis B virus (HBV) co-infected patients.

PMID- 15970351
TI  - Tumor doubling time predicts recurrence after surgery and describes the
      histological pattern of hepatocellular carcinoma on cirrhosis.
AB  - BACKGROUND/AIMS: Recurrence of hepatocellular carcinoma (HCC) following surgical
      resection is influenced by parameters detectable on the resection specimen or
      through a biopsy. The prognostic significance of HCC doubling time (DT) after
      surgery has never been investigated. METHODS: We evaluated 62 patients who
      underwent curative resection of a single HCC on cirrhosis; tumors were assessed
      before surgery on two subsequent occasions with the same imaging technique
      allowing the calculation of DT. The influence of tumor DT, clinical and
      pathological parameters on recurrence-rate and patients survival was assessed
      with uni- and multivariate analysis. Relationship between DT and pathological
      features was also analyzed. RESULTS: Three-year recurrence rate was 32.3% (20
      patients): this was significantly higher in the presence of DT shorter than 100
      days (58 versus 18% when equal to or longer; P=0.008), microvascular invasion (59
      versus 17% when absent; P=0.008) or tumor undifferentiation (54 versus 25% when
      well/moderately differentiated; P=0.015). DT was the only independent predictor
      of recurrence (P=0.005). Patients survival was affected by Child-Pugh class only.
      DT was significantly shorter in tumors with microvascular invasion (P=0.007),
      undifferentiation (P=0.003) and high alpha-fetoprotein levels (P=0.011).
      CONCLUSIONS: DT is easy to estimate and indicates the prognosis of single HCCs
      prior to liver resection.

PMID- 15970352
TI  - Oxidative stress and apoptosis in fetal rat liver induced by maternal
      cholestasis. Protective effect of ursodeoxycholic acid.
AB  - BACKGROUND/AIMS: The sensitivity of fetal rat liver to maternal obstructive
      cholestasis during pregnancy (OCP), and the effect of ursodeoxycholic acid (UDCA)
      were investigated. METHODS: UDCA was administered (i.g. 0.6 mg/kg b.wt./day) from
      day 14 to day 21 of pregnancy after maternal common bile duct ligation. RESULTS:
      Impairment in the activity of antioxidant enzymes, levels of total glutathione
      and GSH/GSSG ratio and the degrees of lipid peroxidation and protein
      carbonylation were similar in livers of OCP mothers and fetuses at term, despite
      hypercholanemia was milder in fetuses. Treatment of OCP rats with UDCA reduced
      maternal and fetal liver oxidative stress. Although maternal hypercholanemia was
      not corrected, fetal serum concentrations of major bile acids (except UDCA and
      beta-muricholic acid) were reduced. Fetal liver expression of key enzyme in bile
      acid synthesis, Cyp7a1, Cyp27 and Cyp8b1 was not affected by OCP or UDCA
      treatment. In OCP fetal livers, the relative expression of Bax-alpha and Bcl-2
      and the activity of caspase-3, but not caspase-8, were increased. These changes
      were markedly reduced in fetuses of OCP animals treated with UDCA. CONCLUSIONS:
      OCP induced moderate fetal hypercholanemia but marked liver oxidative stress and
      apoptosis that were partly prevented by treatment of pregnant rats with UDCA.

PMID- 15970356
TI  - The health workforce: managing the crisis ethical international recruitment of
      health professionals: will codes of practice protect developing country health
      systems?
AB  - Many countries are using the strategy of international recruitment to make up for
      shortages of health professionals to the detriment of health systems in the
      poorest parts of the world. This study reviewed the potential impact of eight
      national level and international codes of practice or similar instruments that
      are being introduced to encourage ethical recruitment in order to protect these
      countries. Whilst effective dissemination of the instruments is generally in
      place, support systems, incentives and sanctions and monitoring systems necessary
      for effective implementation and sustainability are currently weak or have not
      been planned. If such codes or instruments are to be used to protect developing
      country health systems, lessons should be learnt from the early adopters; the
      focus of protecting developing country health systems needs to be emphasised in
      instruments with multiple objectives; the process of implementing the instruments
      strengthened; and internal and external pressure needs to be increased to ensure
      the codes and instruments lead to ethical recruitment and help to protect
      developing country health systems.

PMID- 15970357
TI  - Urocortin reduces the viability of adult rat vascular smooth muscle cells via
      inhibiting L-type calcium channels.
AB  - The newly isolated peptide, urocortin (UCN), is a member of the corticotropin
      releasing factor (CRF)-related peptides that has been found to have potent
      cardiovascular protective effects. In order to investigate the effect of UCN on
      the viability of adult rat vascular smooth muscle cells (VSMC) and the relevant
      mechanisms, we exposed the VSMC to UCN to observe the change in cell viability
      using MTT assay and intracellular calcium concentration using confocal laser
      scanning microscope methods. Our results showed that UCN (10(-7)M) inhibited the
      viability of VSMC by about 26% (P<0.05, compared to control). The effect was
      concentration-dependent, but it was not dependent on the affecting time.
      Glybenclamide (Gly, 10(-5)M), the ATP-sensitive potassium channel (K(ATP)
      channel) blocker, and astressin (10(-6)M), a competitive antagonist of CRF
      receptors, had no influence on this inhibition. Bay K8644 (10(-6)M), a special L
      type calcium channel activator, increased the viability of VSMC. Pre-treatment of
      the cells with UCN diminished the effect of Bay K8644 (n=6, P<0.05). UCN was also
      observed to reduce the intracellular Ca2+ increase induced by KCl and Bay K8644.
      There was no significant difference in nitrite accumulation between UCN groups
      and the control. In conclusion, UCN reduced the viability of VSMC through L-type
      calcium channels. These interesting results might suggest that UCN may be a new
      vasoactive agent involved in hindering vascular remodeling in combination with
      previous reports about UCN's hypotensive effects.

PMID- 15970358
TI  - Peripheral influences on central melanocortin neurons.
AB  - The melanocortins are peptide products of post-translational processing of the
      pro-opiomelanocortin precursor protein. Melanocortin-expressing neurons are found
      in the arcuate nucleus of the hypothalamus and the nucleus of the solitary tract
      in the brain stem. The central melanocortin system is involved in a number of
      biological functions, including regulation of energy homeostasis. Hypothalamic
      and brain stem circuits interpret and integrate a number of peripheral inputs to
      provide a coordinated central response. This review examines the effect of these
      peripheral signals on central melanocortin signaling.

PMID- 15970359
TI  - Immunocytochemical distribution of NK-1 and NK-3 tachykinin receptors in isolated
      pancreatic acini of guinea pigs and rats.
AB  - In this study, we investigated the immunocytochemical distribution of NK-1 and NK
      3 tachykinin receptors in guinea pig and rat isolated pancreatic acini. In
      dispersed acinar cells from guinea pig, immunofluorescence staining detected
      similar densities of NK-1 and NK-3 receptors; conversely, rat acinar cells
      expressed NK-1 receptors more strongly than NK-3 receptors. In line with previous
      functional studies, these immunocytochemical findings suggest that guinea pig NK
      1 and NK-3 receptors and rat NK-1 receptors alone play a direct stimulatory role
      in the basal pancreatic acinar amylase release.

PMID- 15970360
TI  - Enhanced ATP release from rat bladder urothelium during chronic bladder
      inflammation: effect of botulinum toxin A.
AB  - The effects of mechanoreceptor stimulation and subsequent ATP release in
      cyclophosphamide evoked chronic bladder inflammation was examined to demonstrate:
      (1) whether inflammation modulates ATP release from bladder urothelium and (2)
      whether intravesical botulinum toxin A administration inhibits urothelial ATP
      release, a measure of sensory nerve activation. ATP release was measured from rat
      bladders in a Ussing chamber, an apparatus that allows one to separately measure
      resting and mechanoreceptor evoked (e.g. hypoosmotic stimulation) ATP release
      from urothelial and serosal sides of the bladder. Cystometry was utilized to
      correlate changes in ATP release with alterations in the frequency of voiding and
      non-voiding bladder contractions, in vivo measures of bladder afferent activity.
      The resting urothelial release of ATP was not significantly affected by either
      cyclophosphamide or botulinum toxin A treatment. However, evoked ATP release
      following hypoosmotic stimulation was significantly increased (i.e. 94%) in
      chronic cyclophosphamide treated bladder urothelium compared to control bladders.
      In addition, botulinum toxin A treatment significantly reduced hypoosmotic shock
      induced ATP release in cyclophosphamide treated animals by 69%. Cystometry
      revealed that cyclophosphamide and botulinum toxin A treatments altered non
      voiding (i.e. cyclophosphamide increased, botulinum toxin A decreased) but not
      voiding contraction frequency suggesting that alterations in urothelial ATP
      release selectively diminished underlying bladder C-fiber nerve activity.
      Finally, intravesical instillation of botulinum toxin A did not affect ATP
      release from the serosal side implying that its effects were confined to the
      urothelial side of the bladder preparation.

PMID- 15970361
TI  - Passive protection in the infant rat protection assay by sera taken before and
      after vaccination of teenagers with serogroup B meningococcal outer membrane
      vesicle vaccines.
AB  - From a previous published clinical trial among teenagers in Iceland [Perkins BA,
      Jonsdottir K, Briem H, Griffiths E, Plikaytis BD, Hoiby EA, et al. J Infect Dis
      1998;177:683--91], we evaluated a 25% stratified subset of sera, collected before
      vaccination and 6 weeks after the second vaccination with either the Norwegian
      (n=37) or the Cuban (n=35) serogroup B meningococcal outer membrane vesicle (OMV)
      vaccine or the control serogroup A/C capsular polysaccharide vaccine (n=20), for
      protective activity in an infant rat protection assay (IRPA). Protection was
      assessed with both the Norwegian (44/76-SL, B:15:P1.7,16:L3,7) and the Cuban (Cu
      385, B:4:P1.19,15:L3,7) vaccine strain, and the results compared with serum
      bactericidal assay (SBA) titres and anti-OMV IgG antibody concentrations. An IRPA
      response was defined as a >or=10-fold rise in protective activity compared to pre
      vaccination level. Forty-six percent (42/92) of the pre-vaccination sera showed
      protection with strain 44/76-SL compared to only 12% (11/92) with strain Cu 385.
      After the second dose, 22% (8/37) of those given the Norwegian vaccine showed
      IRPA responses with the homologous strain compared to 65% (24/37) in SBA. The
      corresponding numbers with the homologous strain for the Cuban vaccinees were 14%
      (5/35) and 29% (10/35), respectively. Among the controls, 15% (3/20) showed IRPA
      responses to 44/76-SL but none to Cu 385. Correlation between IRPA activity and
      SBA titres or anti-OMV IgG was low, especially for pre-vaccination sera against
      strain 44/76-SL. We conclude that the sensitivity of IRPA described herein may
      not be sufficient to evaluate serogroup B OMV vaccine responses from clinical
      samples.

PMID- 15970362
TI  - Clinical presentations of acute paralytic poliomyelitis.

PMID- 15970363
TI  - Radionuclide migration in forest ecosystems--results of a model validation study.
AB  - The primary objective of the IAEA's BIOMASS Forest Working Group (FWG) was to
      bring together experimental radioecologists and modellers to facilitate the
      exchange of information which could be used to improve our ability to understand
      and forecast radionuclide transfers within forests. This paper describes a blind
      model validation exercise which was conducted by the FWG to test nine models
      which members of the group had developed in response to the need to predict the
      fate of radiocaesium in forests in Europe after the Chernobyl accident. The
      outcomes and conclusions of this exercise are summarised. It was concluded that,
      as a group, the models are capable of providing an envelope of predictions which
      can be expected to enclose experimental data for radiocaesium contamination in
      forests over the time scale tested. However, the models are subject to varying
      degrees of conceptual uncertainty which gives rise to a very high degree of
      divergence between individual model predictions, particularly when forecasting
      edible mushroom contamination. Furthermore, the forecasting capability of the
      models over future decades currently remains untested.

PMID- 15970364
TI  - The practical use of electrets in a public health radon remediation campaign.
AB  - As part of a long-term assessment of domestic radon in Northamptonshire, England,
      a batch of 50 commercially available electrets was deployed for nearly 1,000
      exposures, individual exposure periods ranging from one to eight weeks.
      Responsivity was comparable with that of recently-calibrated Durridge RAD-7
      continuously-monitoring equipment. Voltage history analysis indicated mean
      voltage decay during manufacturers' QA assessment of 0.059+/-0.026 Vday(-1),
      increasing to 0.114+/-0.073 Vday(-1) during storage to first use and to 0.204+/
      0.49 Vday(-1) during inter-deployment storage. At a representative elevated radon
      concentration of 500 Bqm(-3), the resulting perturbation is 3% over a 7-day
      deployment; at the typical mean Northamptonshire level of 80 Bqm(-3) it
      approaches 22%. Each electret can be used for up to 25 measurements, which makes
      the technology attractive for organisational use. It is not suited for deployment
      by individual householders.

PMID- 15970365
TI  - The temporal variations of (7)Be, (210)Pb and (210)Po in air in England.
AB  - We have conducted measurements of naturally occurring radionuclides (7)Be,
      (210)Pb and (210)Po in air at ground level at Chilton, Oxfordshire, England. The
      sampling and analysis regime for the latter two isotopes has been optimised to
      minimise uncertainties in measurement due to decay of (210)Po and in-growth of
      (210)Pb during the sampling and analysis period. Analysis times were reduced by
      using Cerenkov counting to assay the (210)Bi daughter of (210)Pb. Monthly data
      collected over a four-year period are presented and discussed. (7)Be activity
      concentrations appear to peak in spring. (210)Pb activity concentrations also
      follow a seasonal trend reflecting different (222)Rn emanation rates from soil
      during winter and summer. Data for (210)Po show no such trend.

PMID- 15970366
TI  - Heavy metal and Pb isotopic compositions of aquatic organisms in the Pearl River
      Estuary, South China.
AB  - The accumulation of trace metals in aquatic organisms may lead to serious health
      problems through the food chain. The present research project aims to study the
      accumulation and potential sources of trace metals in aquatic organisms of the
      Pearl River Estuary (PRE). Four groups of aquatic organisms, including fish,
      crab, shrimp, and shellfish, were collected in the PRE for trace metal and Pb
      isotopic analyses. The trace metal concentrations in the aquatic organism samples
      ranged from 0.01 to 2.10 mg/kg Cd, 0.02 to 4.33 mg/kg Co, 0.08 to 4.27 mg/kg Cr,
      0.15 to 77.8 mg/kg Cu, 0.17 to 31.0 mg/kg Ni, 0.04 to 30.7 mg/kg Pb, and 8.78 to
      86.3 mg/kg Zn (wet weight). High concentrations of Cd were found in crab, shrimp
      and shellfish samples, while high concentration of Pb was found in fish. In
      comparison with the baseline reference values in other parts of the world, fish
      in the PRE had the highest elevated trace metals. The results of Pb isotopic
      compositions indicated that the bioaccumulation of Pb in fish come from a wide
      variety of food sources and/or exposure pathways, particularly the anthropogenic
      inputs.

PMID- 15970367
TI  - Cognitive behavior therapy for chronic insomnia occurring within the context of
      medical and psychiatric disorders.
AB  - Insomnia is a pervasive problem for many patients suffering from medical and
      psychiatric conditions. Even when the comorbid disorders are successfully
      treated, insomnia often fails to remit. In addition to compromising quality of
      life, untreated insomnia may also aggravate and complicate recovery from the
      comorbid disease. Cognitive behavior therapy for insomnia (CBT-I) has an
      established efficacy for primary insomnia, but less is known about its efficacy
      for insomnia occurring in the context of medical and psychiatric conditions. The
      purpose of this article is to present a rationale for using CBT-I in medical and
      psychiatric disorders, review the extant outcome literature, highlight
      considerations for adapting CBT-I procedures in specific populations, and suggest
      directions for future research. Outcome studies were identified for CBT-I in
      mixed medical and psychiatric conditions, cancer, chronic pain, HIV, depression,
      posttraumatic stress disorder, and alcoholism. Other disorders discussed include:
      bipolar disorder, eating disorders, generalized anxiety, and obsessive compulsive
      disorder. The available data demonstrate moderate to large treatment effects
      (Cohen's d, range=0.35-2.2) and indicate that CBT-I is a promising treatment for
      individuals with medical and psychiatric comorbidity. Although the literature
      reviewed here is limited by a paucity of randomized, controlled studies, the
      available data suggest that by improving sleep, CBT-I might also indirectly
      improve medical and psychological endpoints. This review underscores the need for
      future research to test the efficacy of adaptations of CBT-I to disease specific
      conditions and symptoms.

PMID- 15970368
TI  - Inhibitory effects of long-term administration of ferulic acid on astrocyte
      activation induced by intracerebroventricular injection of beta-amyloid peptide
      (1-42) in mice.
AB  - Accumulating evidence indicates that glial cells are actively involved in the
      pathogenesis of Alzheimer's disease. We recently reported protective effects of
      long-term administration of ferulic acid against learning and memory deficit
      induced by centrally administered beta-amyloid peptide (Abeta)1-42 in mice. In
      that report, we found that the Abeta1-42-induced increases in immunoreactivities
      of glial fibrillary acidic protein, the astrocyte marker, and interleukin(IL)
      1beta in the hippocampus are also suppressed by pretreatment with ferulic acid.
      In the present study, we aimed to further characterize the effect of long-term
      administration of ferulic acid on the centrally administered Abeta1-42-induced
      activation of glial cells in mice. Mice were allowed free access to drinking
      water (control) or water containing ferulic acid (0.006%) for 4 weeks, and then
      Abeta1-42 (410 pmol) was administered via intracerebroventricular injection.
      Intracerebroventricularly injected Abeta1-42 induced an increase in
      immunoreactivities of endothelial nitric oxide synthase (eNOS) and 3
      nitrotyrosine (3-NT) in the activated astrocytes in the hippocampus. Pretreatment
      of ferulic acid for 4 weeks prevented the Abeta1-42-induced increase in eNOS and
      3-NT immunoreactivities. Administration of ferulic acid per se induced a
      transient and slight increase in eNOS immunoreactivity in the hippocampus on day
      14, which returned to basal levels on day 28. Intracerebroventricularly injected
      Abeta1-42 also increased interleukin-1alpha(IL-1alpha) immunoreactivity in the
      hippocampus, which was also suppressed by pretreatment with ferulic acid. These
      results demonstrate that long-term administration of ferulic acid induces
      suppression of the centrallly injected Abeta1-42-induced activation of astrocytes
      which is suggested to underlie the protective effect of ferulic acid against
      Abeta1-42 toxicity in vivo.

PMID- 15970369
TI  - Tolerability of cyclosphosphamide and methotrexate induction immunosuppression in
      nonhuman primates.
AB  - Transplantation in nonhuman primates, in particular using solid organs from
      porcine donors, requires an efficacious induction immunosuppression. Besides
      biologicals, the low molecular weight drugs used include cyclophosphamide (CyP)
      and methotrexate (MTX). As these compounds generally have a narrow therapeutic
      window, we performed tolerability studies in baboons and cynomolgus monkeys,
      with/without maintenance immunosuppressants such as cyclosporine A, everolimus,
      mycophenolate sodium and FTY720. In both species, a four-dose CyP regimen of 40,
      20, 30 and 30 mg/kg i.v. on days 1, 2, 4 and 6 is not tolerated, but the regimen
      is tolerated upon individual adjustment of the third and fourth dose to 18-25 and
      8-20mg/kg, respectively, based on white blood cell count. In cynomolgus monkeys,
      a 5-day course of MTX i.v. at 0.5 mg/(kg d) is well tolerated, but not MTX at 1.0
      mg/(kg d); in combination with maintenance immunosuppression, the 0.5mg/(kg d)
      dose can cause adverse effects. Combinations of CyP and MTX are tolerated using
      the 5-day course of MTX at 0.25 mg/(kg d) and a four-dose regimen of CyP at 10,
      2.5, 7.5 and 7.5 mg/kg. These regimens are tolerated in combination with
      maintenance immunosuppressants. The data provide base values for investigators
      using nonhuman primates in experimental studies, particularly in
      xenotransplantation requiring effective induction immunosuppression that is close
      to maximum tolerated dose levels.

PMID- 15970370
TI  - Ultrafine titanium dioxide particles in the absence of photoactivation can induce
      oxidative damage to human bronchial epithelial cells.
AB  - Ultrafine titanium dioxide (TiO(2)) particles have been shown to exhibit strong
      cytotoxicity when exposed to UVA radiation, but are regarded as a biocompatible
      material in the absence of photoactivation. In contrast to this concept, the
      present results indicate that anatase-sized (10 and 20 nm) TiO(2) particles in
      the absence of photoactivation induced oxidative DNA damage, lipid peroxidation,
      and micronuclei formation, and increased hydrogen peroxide and nitric oxide
      production in BEAS-2B cells, a human bronchial epithelial cell line. However, the
      treatment with anatase-sized (200 and >200 nm) particles did not induce oxidative
      stress in the absence of light irradiation; it seems that the smaller the
      particle, the easier it is for the particle to induce oxidative damage. The
      photocatalytic activity of the anatase form of TiO(2) was reported to be higher
      than that of the rutile form. In contrast to this notion, the present results
      indicate that rutile-sized 200 nm particles induced hydrogen peroxide and
      oxidative DNA damage in the absence of light but the anatase-sized 200nm
      particles did not. In total darkness, a slightly higher level of oxidative DNA
      damage was also detected with treatment using an anatase-rutile mixture than with
      treatment using either the anatase or rutile forms alone. These results suggest
      that intratracheal instillation of ultrafine TiO(2) particles may cause an
      inflammatory response.

PMID- 15970371
TI  - Performance of methods of occlusal caries detection in permanent teeth under
      clinical and laboratory conditions.
AB  - OBJECTIVES: To compare performance of visual inspection and Laser fluorescence
      methods to detect occlusal caries lesions under clinical and laboratory
      conditions in permanent teeth. METHODS: One hundred and ten sites in 57 third
      molars scheduled for extraction were examined with visual inspection and laser
      fluorescence (DIAGNOdent) device by two trained examiners. After the extraction,
      teeth were re-examined. Then, teeth were sectioned to perform histological
      validation. Best cut-off points were calculated with ROC analysis, and
      sensitivity, specificity and accuracy were calculated at D2 and D3 thresholds.
      Comparisons between the methods and conditions of examination were performed
      using McNemar test. Inter-examiner agreement in the same conditions and agreement
      between the methods performed in vivo and in vitro conditions were assessed by
      Kappa test. Laser fluorescence values obtained in two conditions were compared
      with Wilcoxon test. RESULTS: No difference was observed with visual inspection in
      both conditions. Laser fluorescence performed in vitro presented higher
      specificity and accuracy at D3 threshold. Visual inspection showed higher
      reproducibility. After adjustment of cut-off points for laser fluorescence
      method, there was no difference between the evaluated parameters. CONCLUSION:
      Only slightly differences were observed between the examinations performed under
      clinical and laboratory conditions in the detection of occlusal caries lesions in
      permanent teeth.

PMID- 15970372
TI  - Up- and down-regulating facial disgust: affective, vagal, sympathetic, and
      respiratory consequences.
AB  - Relative to watching in a natural manner, people asked to suppress or exaggerate
      their facial response to a negative emotional stimulus experience greater
      activation of the sympathetic nervous system but report a similar subjective
      emotional experience. The present research extends prior research on response
      modulation in two important ways. First, discrete indicators of cardiac vagal and
      sympathetic control (respiratory sinus arrhythmia (RSA) and pre-ejection period
      (PEP), respectively) were included as dependent measures along with interbeat
      interval (IBI) and skin conductance (EDR). Second, to help generalize results
      across response-focused modulation techniques, participants suppressed,
      exaggerated, or exerted no control over their responses while watching a disgust
      eliciting film (for control purposes, a fourth group was asked to watch a neutral
      film naturally). Response modulation was associated with significantly decreased
      PEP (increased cardiac sympathetic control) relative to those in the natural
      watch conditions. All participants evidenced increased EDR while watching the
      disgusting clip, but facial modulation did not produce EDR reactivity beyond that
      of watching the disgusting film naturally. Exaggerators experienced decreased IBI
      during modulation (perhaps due to increased muscle contraction) whereas all other
      groups showed increased IBI (i.e., the orienting response). Neither emotional
      experience nor facial modulation reliably impacted RSA, respiration rate, or
      inspiratory depth.

PMID- 15970373
TI  - Mutagenesis studies toward understanding the mechanism of the cofactor function
      of thrombomodulin.
AB  - Thrombomodulin (TM) is as essential cofactor in protein C activation by thrombin.
      To investigate the cofactor effect of TM on the P3-P3' binding specificity of
      thrombin, we prepared a Gla-domainless protein C (GDPC) and an antithrombin (AT)
      mutant in which the P3-P3' residues of both molecules were replaced with the
      corresponding residues of the factor Xa cleavage site in prethrombin-2. TM is
      known to interact with GDPC, but not AT in the complex. Thrombin did not react
      with either mutant in the absence of a cofactor. While the thrombin-TM complex
      also did not react with the AT mutant, it activated the GDPC mutant with a normal
      k(cat), but an approximately 4-fold impaired K(m) value. Further studies revealed
      that the active-site directed inhibitor p-aminobenzamidine acts as a competitive
      inhibitor of both wild-type and GDPC mutant in reaction with the thrombin-TM
      complex. These results suggest that the interaction of the P3-P3' residues of
      GDPC with the active-site pocket of the thrombin-TM complex makes a dominant
      contribution to the binding specificity of the reaction. Moreover, the
      observation that the GDPC mutant, but not the AT mutant, functions as an
      effective substrate for the thrombin-TM complex suggests that GDPC interaction
      with the thrombin-TM complex may be associated with the alteration of the
      conformation of the P3-P3' residues of the substrate.

PMID- 15970374
TI  - Dorsal onlay graft urethroplasty using penile skin or buccal mucosa for repair of
      bulbar urethral stricture: results of a prospective single center study.
AB  - OBJECTIVE: To compare the outcomes of dorsal onlay graft urethroplasty using
      penile skin (PS) or buccal mucosa (BM) free grafts in the repair of adult
      bulbourethral strictures. METHODS: From January 1998 to March 2003, 30 patients
      with bulbar urethral strictures underwent urethral reconstruction with PS (17) or
      with BM free graft (13). Follow-up was done at 6, 12 and 18 months
      postoperatively, and every year subsequently. Success was defined as
      normalization of IPSS and a stable Q(max) value >20 ml/s. Any further
      instrumentation for stricture recurrence was considered a failure. RESULTS: Mean
      follow-up was 51 months (20-74). The overall success rate was 80% (85% in the BM
      and 76% in the PS group). Improvement of uroflowmetry, IPSS and QoL did not show
      a significant difference between the two groups. A significant improvement of the
      orgasmic function domain of the IIEF was found in patients treated with a PS
      graft. Post-operative complications were lip hypoesthesia (30%), retraction of
      the ventral skin of the penis (7%), post-voiding dribbling (8% with BM graft, and
      7%, with PS graft). Six patients, 2 with BM (15%) and 4 with PS graft patch (24%)
      required further treatment due to stricture recurrence. CONCLUSION: Results of PS
      or BM graft are comparable at 18 month follow-up, although orgasmic function is
      significantly improved in patients receiving a PS graft. Nevertheless, with
      extended follow-up, the use of PS seems to be associated with a higher failure
      rate.

PMID- 15970375
TI  - One trocar laparoscopic placement of peritoneal shunt for hydrocephalus: A
      simplified technique.
AB  - Peritoneal catheter placement for the treatment of hydrocephalus can nowadays be
      performed laparoscopically. We report our experience using a single trocar
      technique, with emphasis to a modification applied especially for the obese
      patients.

PMID- 15970376
TI  - Significance of cyclooxygenase 2 and MDR1/P-glycoprotein coexpression in ovarian
      cancers.
AB  - Immunohistochemical analysis of prognostic significance of COX-2 and P-gp
      expression in ovarian cancers was performed on samples originating from 73
      tumors. COX-2-positive cases were shown to demonstrate higher expression of P-gp.
      The studies demonstrated also that, higher P-gp expression was typical for cases
      which responded poorly to chemotherapy and for cases with shorter progression
      free time. Expression of COX-2 predisposed to a more rapid disease progression.
      The study documented a relationship between COX-2 and P-gp suggesting that COX-2
      inhibitors might investigated in clinical trials as a treatment supplementary to
      chemotherapy of ovarian cancers.

PMID- 15970377
TI  - Effects of electroacupuncture on expression of somatostatin and
      preprosomatostatin mRNA in dorsal root ganglions and spinal dorsal horn in
      neuropathic pain rats.
AB  - Somatostatin (SOM) is an endogenous non-opioid neuropeptide that has analgesic
      effect in rodents and human beings. Previous studies indicated that SOM might be
      involved in the modulating effects of electroacupuncture (EA). Using
      immunohistochemistry and RT-PCR, the present study observed the effects of EA on
      the expression of SOM peptide and preprosomatostatin (ppSOM) mRNA in a rat model
      of neuropathic pain induced by chronic constriction injury (CCI) to the sciatic
      nerve. No significant change was detected in the expression of SOM and ppSOM mRNA
      following CCI. However, EA could significantly enhance SOM expression in dorsal
      root ganglion (DRG) and spinal dorsal horn as well as ppSOM mRNA level in DRG of
      neuropathic pain rats. The present data demonstrated that EA could activate
      endogenous SOM of neuropathic pain rats and this might be one of the mechanisms
      that underlie the effectiveness of EA in the treatment of neuropathic pain.

PMID- 15970378
TI  - Protective effect of melatonin against head trauma-induced hippocampal damage and
      spatial memory deficits in immature rats.
AB  - It is well known that head trauma induces the cognitive dysfunction resulted from
      hippocampal damage. In the present study, we aimed to demonstrate the effect of
      melatonin on hippocampal damage and spatial memory deficits in 7-day-old rat pups
      subjected to contusion injury. Melatonin was injected intraperitoneally at the
      doses of 5 or 20 mg/kg of body weight immediately after induction of traumatic
      injury. Hippocampal damage was examined by cresyl violet staining and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
      Spatial memory performance was assessed in the Morris water maze. Melatonin
      significantly attenuated trauma-induced neuronal death in hippocampal CA1, CA3
      regions and dentate gyrus, and improved spatial memory deficits, which was
      equally effective at doses of 5-20 mg/kg. The present results suggest that
      melatonin is a highly promising agent for preventing the unfavorable outcomes of
      traumatic brain injury in young children.

PMID- 15970379
TI  - Functional architecture of the mammalian striatum: mouse vascular and striosome
      organization and their anatomic relationships.
AB  - To determine whether the general architecture of striatal vessels and mu opioid
      receptor-rich striosomes is similar, we investigated 3D reconstructions of
      coronal sections in 10 FVB mice. The sections were stained for striosomes using a
      mu opioid receptor antibody (MOR1). We used computerized procedures to detect
      striosomes and vessels and to calculate volume, number and colocalization of
      striosomes and vessels. The results showed a lattice-like pattern of striosomes
      similar to, and often surrounding, blood vessels. Furthermore, co-localization
      calculations suggested that the striosomes are more vascular than the matrix.
      Vessel volume was 5.0+/-1.3% per microm3 in striosomes versus 3.6+/-0.9%microm3
      in matrix (p=0.01). The findings emphasize the probable importance of a grid- or
      lattice-like structure as an organizing principle of striatal anatomy and
      function. In addition, the greater vascularity of the striosomes compared to the
      matrix suggests a unique function of this compartment in relation to humoral
      signals and neurotropic drugs.

PMID- 15970380
TI  - EphB2 induces proliferation and promotes a neuronal fate in adult subventricular
      neural precursor cells.
AB  - The subventricular germinal zone (SVZ) retains an active population of stem cells
      and neural precursor cells throughout adulthood. EphrinB signaling mediates
      angiogenesis and vasculogenesis in the developing and adult brain. Recent studies
      indicate that molecules involved in angiogenesis often influence neurogenesis as
      well. However, little work has been done considering a role for EphB2/EphrinB in
      adult neural precursor cells. We therefore examined whether the EphB2 receptor
      tyrosine kinase could directly effect proliferation of SVZ neural precursors
      and/or direct the cell fate of SVZ cells in vitro. Here, we found that clustered
      EphB2 increased bromodeoxyuridine (BrdU) incorporation and proliferation of SVZ
      neurosphere cultures. Immunostaining and RT-PCR analysis for beta-tubulin III
      (Tuj1) and GFAP indicated 4-day treatment with EphB2 promoted a neuronal
      phenotype, suggesting that the EphB2 receptor might also direct SVZ cell fate.
      EphB2 transiently down-regulated SVZ cell mRNA of Notch1 and Zic1, genes that
      regulate neurogenesis and neuronal differentiation. Notch1 has been implicated in
      apoptosis of neural precursors, however, a cell viability assay revealed no
      statistical difference between EphB2-treated and control cultures. When SVZ
      neurospheres were cultured upon Matrigel, EphB2 attenuated radial migration of
      SVZ cells in vitro. These results demonstrate that EphB2/EphrinB signaling
      directly induces SVZ proliferation, decreases migration, and promotes a neuronal
      fate of SVZ neural precursors independent of cell survival.

PMID- 15970381
TI  - Visual attention deficits in Alzheimer's disease: an fMRI study.
AB  - Cognitive and neuroscience studies indicate that attentional operations are
      impaired in Alzheimer's disease (AD). Our goal was to define the anatomical areas
      of activation associated with visual attention processing and to define deficits
      or changes that may occur in AD patients compared with control group. Thirteen AD
      patients and 13 age- and education-matched normal controls were tested in two
      visual search tasks (one was a conjunction task, where feature binding is
      required. The other was a subset task, where group stimuli is needed without
      feature binding) using fMRI techniques. After stereotactical normalization, voxel
      by-voxel t statistics was used to compare activated brain areas between patients
      and control subjects. Our findings suggest that both search tasks are controlled
      by partially overlapping cerebral networks, including parietal, frontal and
      occipital-temporal cortical regions and primary visual cortex. The AD patient
      group showed less activation in both parietal lobes and the left frontal regions,
      while increased activation was found in the right frontal lobes and the right
      occipito-temporal cortical regions with the conjunction task. In the subset task,
      decreased activation in AD patients was seen in the left parietal lobe and
      bilateral frontal lobes, while increased activation was seen in both medial
      temporal lobes. In addition, for the comparison between tasks, The difference is
      very small for AD patients. Control group showed a higher amplitude in the right
      prefrontal region, temporal cortical regions and parietal lobe. These results
      indicate that attention deficits in AD patients may be attributed to both binding
      problem and grouping inefficiency.

PMID- 15970382
TI  - Suppression of postsynaptic density protein 95 by antisense oligonucleotides
      diminishes postischemic pyramidal cell death in rat hippocampal CA1 subfield.
AB  - Our previous investigation has shown that postsynaptic density protein 95 (PSD
      95) is critical for the Src family kinases-mediated tyrosine phosphorylation of N
      methyl-d-aspartate receptor subunit 2A (NR2A) in the postischemic hippocampus. To
      clarify the roles of PSD-95 in the ischemic brain damage, histological method was
      performed to examine the effects of PSD-95 antisense oligonucleotides (AS) on the
      postischemic delayed cell death in rat hippocampus. Transient (15 min) brain
      ischemia was induced by the four-vessel occlusion method in Sprague-Dawley rats.
      Five days of reperfusion following brain ischemia (I/R5d) led to hippocampal CA1
      pyramidal cell death upward of 90%. Intracerebroventricular infusion of AS (every
      24 h for 3 days before ischemia) not only decreased the PSD-95 expression but
      also increased the number of surviving pyramidal neurons, while missense
      oligonucleotides (MS) had no effects. To further investigate the mechanisms
      underlying the neuroprotection of PSD-95 deficiency, the interaction of proline
      rich tyrosine kinase 2 (Pyk2) with NR2A as well as autophosphorylation (Tyr402)
      of Pyk2 were detected. Immunoprecipitation and immunoblot analysis showed that
      preischemic treatment with AS, but not MS or vehicle, attenuated the I/R6h
      induced increases in Pyk2-NR2A association and Pyk2 autophosphorylation. The
      protein levels of NR2A and Pyk2 had no differences under the above conditions.
      Our data suggest that the recruitments of ion channels and signaling molecules
      may be involved in the PSD-95 neurotoxicity in the postischemic hippocampus.

PMID- 15970383
TI  - Alteration of extracellular collagen matrix in the myocardium of canines infected
      with Dirofilaria immitis.
AB  - The heart consists of cardiocytes and the interstitial extracellular matrix
      (ECM), which is made up mainly of collagens. The ECM has been suggested to be
      important in maintaining the structure and function of the heart. This
      investigation attempted to elucidate the changes in the ECM collagens in the
      hearts of canines with dirofilariasis. The ECM collagen fibrils of the heart are
      grouped into endomysial struts, epimysial weaves, and perimysial coils. In the
      present study, we used the modified silver impregnation technique to stain
      paraffin-embedded sections to demonstrate three types of ECM. The results
      revealed that the ECM content of the heart was significantly reduced in heartworm
      infected dogs, and became fragmented and dissociated. In addition, the amounts of
      collagen in the septum (Sep), RVs and LVs in canines with dirofilariasis
      (Sep=11.55+/-0.65, RV=12.07+/-0.59, LV=11.72+/-0.62 microg/mg, n=24) were
      significantly lower (p<0.01) than that in the normal canines (Sep=15.09+/-0.72,
      RV=15.16+/-0.83, LV=14.91+/-0.89 microg/mg, n=8). These results indicated that
      heartworm infection induced the remodeling of the extracellular matrix, thus
      markedly altering the architecture and function of the heart.

PMID- 15970384
TI  - The broad spectrum of Trichinella hosts: from cold- to warm-blooded animals.
AB  - In recent years, studies on Trichinella have shown that the host range is wider
      than previously believed and new Trichinella species and genotypes have been
      described. Three classes of vertebrates are known to act as hosts, mammals, birds
      and reptiles, and infected vertebrates have been detected on all continents but
      Antarctica. Mammals represent the most important hosts and all Trichinella
      species are able to develop in this vertebrate class. Natural infections with
      Trichinella have been described in more than 150 mammalian species belonging to
      12 orders (i.e., Marsupialia, Insectivora, Edentata, Chiroptera, Lagomorpha,
      Rodentia, Cetacea, Carnivora, Perissodactyla, Artiodactyla, Tylopoda and
      Primates). The epidemiology of the infection greatly varies by species relative
      to characteristics, such as diet, life span, distribution, behaviour, and
      relationships with humans. The non-encapsulated species Trichinella
      pseudospiralis, detected in both mammals (14 species) and birds (13 species),
      shows a cosmopolitan distribution with three distinguishable populations in the
      Palearctic, Nearctic and Australian regions. Two additional non-encapsulated
      species, Trichinella papuae, detected in wild pigs and saltwater crocodiles of
      Papua New Guinea, and Trichinella zimbabwensis, detected in farmed Nile
      crocodiles of Zimbabwe, can complete their life cycle in both mammals and
      reptiles. To the best of our knowledge, T. papuae and T. zimbabwensis are the
      only two parasites known to complete their entire life cycle independently of
      whether the host is warm-blooded or cold-blooded. This suggests that these two
      Trichinella species are capable of activating different physiological mechanisms,
      according to the specific vertebrate class hosting them.

PMID- 15970385
TI  - Evaluation of three enzyme-linked immunosorbent assays for detection of
      antibodies to Neospora caninum in bulk milk.
AB  - Three ELISAs for the detection of antibodies against Neospora caninum in bulk
      milk were evaluated in 162 Dutch dairy herds. The first ELISA was the Dutch
      Animal Health Service (AHS) in-house ELISA, developed from the routine in-house
      serum ELISA. The other two ELISAs were commercial milk ELISAs from IDEXX and LSI.
      Blood samples of all lactating cows in 162 dairy herds were tested using the AHS
      in-house serum ELISA. Based on previous studies in the Netherlands a within-herd
      N. caninum seroprevalence of 15% was associated with increased risk for
      reproductive losses. This percentage was therefore used as positive
      seroprevalence cut-off value. Repeatability of the ELISAs was evaluated by
      testing on three different days. The AHS in-house ELISA lacked specificity,
      probably due to use of a different batch of antigen on the second and third test
      day. Cut-off values were determined using misclassification costs term
      calculations. At cut-off values 0.6 for the IDEXX and 0.2 for the LSI, a herd
      sensitivity of 61% (95% CI: 49--73%) and 47% (95% CI: 35--60%) was estimated.
      Herd specificity at these cut-off values was 92% (95% CI: 87--98%) for the IDEXX
      and 94% (95% CI: 90--99%) for the LSI ELISA. The positive and negative predictive
      values were 84% (95% CI: 68--100%) and 86% (95% CI: 79--94%) for the IDEXX ELISA,
      and 85% (95% CI: 67--100%) and 82% (95% CI: 74--90%) for the LSI ELISA. The
      agreement between all possible combinations of test-days was expressed by kappa
      values. These were found to be slightly higher for the IDEXX than for the LSI
      ELISA. It is concluded that both commercial ELISAs performed satisfactorily to
      detect a within-herd seroprevalence of N. caninum in lactating cows of at least
      15%.

PMID- 15970386
TI  - Evidence to support horses as natural intermediate hosts for Sarcocystis neurona.
AB  - Opossums (Didelphis spp.) are the definitive host for the protozoan parasite
      Sarcocystis neurona, the causative agent of equine protozoal myeloencephalitis
      (EPM). Opossums shed sporocysts in feces that can be ingested by true
      intermediate hosts (cats, raccoons, skunks, armadillos and sea otters). Horses
      acquire the parasite by ingestion of feed or water contaminated by opossum feces.
      However, horses have been classified as aberrant intermediate hosts because the
      terminal asexual sarcocyst stage that is required for transmission to the
      definitive host has not been found in their tissues despite extensive efforts to
      search for them [Dubey, J.P., Lindsay, D.S., Saville, W.J., Reed, S.M.,
      Granstrom, D.E., Speer, C.A., 2001b. A review of Sarcocystis neurona and equine
      protozoal myeloencephalitis (EPM). Vet. Parasitol. 95, 89-131]. In a 4-month-old
      filly with neurological disease consistent with EPM, we demonstrate schizonts in
      the brain and spinal cord and mature sarcocysts in the tongue and skeletal
      muscle, both with genetic and morphological characteristics of S. neurona. The
      histological and electron microscopic morphology of the schizonts and sarcocysts
      were identical to published features of S. neurona [Stanek, J.F., Dubey, J.P.,
      Oglesbee, M.J., Reed, S.M., Lindsay, D.S., Capitini, L.A., Njoku, C.J., Vittitow,
      K.L., Saville, W.J., 2002. Life cycle of Sarcocystis neurona in its natural
      intermediate host, the raccoon, Procyon lotor. J. Parasitol. 88, 1151-1158]. DNA
      from schizonts and sarcocysts from this horse produced Sarcocystis specific 334bp
      PCR products [Tanhauser, S.M., Yowell, C.A., Cutler, T.J., Greiner, E.C., MacKay,
      R.J., Dame, J.B., 1999. Multiple DNA markers differentiate Sarcocystis neurona
      and Sarcocystis falcatula. J. Parasitol. 85, 221-228]. Restriction fragment
      length polymorphism (RFLP) analysis of these PCR products showed banding patterns
      characteristic of S. neurona. Sequencing, alignment and comparison of both
      schizont and sarcocyst DNA amplicons showed 100% identity. Although Koch's
      postulates have not been demonstrated in this case study, the finding of mature,
      intact S. neurona schizonts and sarcocysts in the tissues of this single horse
      strongly suggests that horses have the potential to act as intermediate hosts.
      Further studies are needed to demonstrate Koch's postulates with repeated
      transfer of S. neurona between opossums and horses.

PMID- 15970387
TI  - HPLC purification of recombinant NcGRA6 antigen improves enzyme-linked
      immunosorbent assay for serodiagnosis of bovine neosporosis.
AB  - The gene for a dense granule protein (NcGRA6) of Neospora caninum was expressed
      in Escherichia coli as a His-tag fusion protein and purified by NiNTA affinity
      chromatography. In a preliminary study, high binding of antibodies from N.
      caninum-negative cows was observed in enzyme-linked immunosorbent assay (ELISA)
      using NiNTA-purified NcGRA6. Analysis of NiNTA eluates revealed a significant
      number of E. coli proteins that co-purified with recombinant NcGRA6. In an
      attempt to improve the relative sensitivity and specificity of the NcGRA6-based
      ELISA, the rNcGRA6 eluates were subjected to a secondary purification using
      reverse phase-high performance liquid chromatography (RP-HPLC). Analysis of RP
      HPLC eluates by SDS-PAGE/silver staining revealed the purification of recombinant
      NcGRA6 from contaminating E. coli proteins. ELISAs using the RP-HPLC purified
      NcGRA6 (dELISA) or singly purified NcGRA6 (sELISA) for identifying seropositive
      and seronegative cows in a beef herd experiencing an epidemic outbreak of
      neosporosis were compared to standard assays based on native tachyzoite protein
      immunofluorescence antibody test, immunoblot assay, and ISCOM-ELISA. The relative
      sensitivity, specificity, and kappa value of the NcGRA6d-ELISA were greatly
      improved over the NcGRA6s-ELISA when compared to the three native antigen
      immunoassays. These results indicate that removal of contaminating E. coli
      proteins improves the performance of recombinant NcGRA6 ELISA in diagnosing
      bovine neosporosis, and may have applicability to the use of recombinant proteins
      in diagnosing other infectious agents.

PMID- 15970388
TI  - The effectiveness of copper oxide wire particles as an anthelmintic in pregnant
      ewes and safety to offspring.
AB  - The objective of the experiment was to determine the effectiveness of copper
      oxide wire particles (COWP) in pregnant ewes and safety to lambs. COWP have been
      used recently as an anthelmintic in small ruminants to overcome problems
      associated with nematode resistance to chemical dewormers. Doses of COWP (<or=4
      g) have been used in lambs without clinical signs of copper toxicity. Use in
      pregnant ewes has not been examined. Mature Katahdin ewes were administered 0
      (n=14), 2 (n=15), or 4 (n=15)g of COWP 33+/-1.6 days before lambing in late March
      2004. Fecal egg counts (FEC) and blood packed cell volume (PCV) were determined
      between Days 0 (day of COWP administration) and 35. Lambs were weighed within 24h
      after birth, at 30 and 60 days of age, and in mid-September ( approximately 120
      days of age). Blood was collected from lambs within 24h after birth and at 30
      days of age for determination of the activity of the liver enzyme, aspartate
      aminotransferase (AST) in plasma. Within 7 days after COWP administration, FEC
      decreased by 1308 and 511 eggs/g (epg) in the 2 and 4 g groups, respectively,
      compared with an increase of 996 epg in the control group (P<0.02). PCV was
      similar among groups between Days 0 and 35. Lamb plasma AST activity at birth
      increased with increasing dose of COWP in dams (P<0.001). Plasma AST activity at
      30 days of age was similar for lambs from ewes treated with 0 and 2g COWP, but
      was slightly greater in lambs from ewes treated with 4 g COWP (P<0.02). Birth
      weights decreased with increasing COWP (P<0.003). By 30 (COWPxbirth type, P<0.02)
      and 60 (COWPxbirth type, P<0.02) days of age, weight of multiple-born lambs
      decreased with increasing COWP, while weight of single-born lambs was similar
      among treatments. In mid-September ( approximately 120 days of age) weights of
      multiple-born lambs from ewes treated with 4 g COWP tended to be lightest
      compared with lambs from ewes treated with 0 or 2g COWP or single-born lambs
      (P<0.09). Lamb survival to 30, 60, or 120 days of age was not affected by COWP
      treatment to ewes. Administration of 4 g COWP to late pregnant ewes may
      negatively impact multiple-born offspring, but the 2g appears to be safe for
      production.

PMID- 15970389
TI  - Full thickness abdominal burn following magnetic resonance guided focused
      ultrasound therapy.

PMID- 15970390
TI  - Cortisol awakening response in pregnant women.
AB  - In this study, basal saliva cortisol was determined in women at 32 weeks of
      pregnancy and again at 9 months post-partum. During pregnancy, the cortisol
      levels of the 119 subjects were found to be elevated, with noon and evening
      levels more than twice as high as during the non-pregnant state. Despite the
      hypercortisolism, the cortisol awakening response was still present during
      pregnancy. Although the absolute mean increase in cortisol at 30 min post
      awakening was larger during pregnancy, the relative mean increase was around 40%
      of the awakening level in both cases. The cortisol awakening response was not
      correlated between pregnancy and the post-partum, showing a lack of stability
      over the 11-month period. Finally, both in the pregnant and non-pregnant states,
      the magnitude of the cortisol awakening response was not related to time of
      awakening, nor to anticipation of a working vs. non-working day. In conclusion,
      the free cortisol awakening response is present during pregnancy, and is
      potentially a useful marker to study the association between prenatal
      psychosocial stress and offspring development.

PMID- 15970391
TI  - Stress, sensitisation and somatisation: a special issue in honour of Holger
      Ursin.

PMID- 15970392
TI  - Weight loss strategies, stress, and cognitive function: supervised versus
      unsupervised dieting.
AB  - The early stages of dieting to lose weight have been associated with neuro
      psychological impairments. Previous work has not elucidated whether these
      impairments are a function solely of unsupported or supported dieting. Raised
      cortico-steroid levels have been implicated as a possible causal mechanism.
      Healthy, overweight, pre-menopausal women were randomised to one of three
      conditions in which they dieted either as part of a commercially available weight
      loss group, dieted without any group support or acted as non-dieting controls for
      8 weeks. Testing occurred at baseline and at 1, 4 and 8 weeks post baseline.
      During each session, participants completed measures of simple reaction time,
      motor speed, vigilance, immediate verbal recall, visuo-spatial processing and (at
      Week 1 only) executive function. Cortisol levels were gathered at the beginning
      and 30 min into each test session, via saliva samples. Also, food intake was self
      recorded prior to each session and fasting body weight and percentage body fat
      were measured at each session. Participants in the unsupported diet condition
      displayed poorer vigilance performance (p = 0.001) and impaired executive
      planning function (p = 0.013) (along with a marginally significant trend for
      poorer visual recall (p = 0.089)) after 1 week of dieting. No such impairments
      were observed in the other two groups. In addition, the unsupported dieters
      experienced a significant rise in salivary cortisol levels after 1 week of
      dieting (p < 0.001). Both dieting groups lost roughly the same amount of body
      mass (p = 0.011) over the course of the 8 weeks of dieting, although only the
      unsupported dieters experienced a significant drop in percentage body fat over
      the course of dieting (p = 0.016). The precise causal nature of the relationship
      between stress, cortisol, unsupported dieting and cognitive function is, however,
      uncertain and should be the focus of further research.

PMID- 15970393
TI  - Reducing heavy drinking in college males with the decisional balance: analyzing
      an element of Motivational Interviewing.
AB  - The decisional balance, a brief detailing of the advantages and disadvantages of
      behavior change, serves as a key component to interventions in Motivational
      Interviewing. The impact of this component alone is not well understood. Forty
      seven men completed a Timeline Followback interview assessing alcohol consumption
      and unsafe sexual practices. They then completed a decisional balance, listing
      the Pros and Cons of decreasing their drinking, but not one for safer sex. One
      month follow-up data showed that they had statistically significant and
      clinically meaningful increases in their motivation to alter drinking and
      decreases in the number of drinks that they intended to drink, the actual drinks
      consumed per month, the days per month that they drank, their maximum number of
      drinks consumed on one occasion, and their average number of drinks per occasion.
      They did not alter their sexual behavior or their motivation to increase safe sex
      behavior. These results suggest that the decisional balance plays an important
      role in Motivational Interviewing and could serve as a quick and efficient
      intervention by itself.

PMID- 15970394
TI  - A longitudinal examination of the link between parent alcohol problems and youth
      drinking: the moderating roles of parent and child gender.
AB  - The unique and interactive effects of paternal and maternal alcohol problems on
      the drinking behavior of adolescent girls and boys were investigated. A
      prospective design was employed to examine changes in youth drinking behavior
      over a 3-year period in a community-based sample of 695 families. Results
      revealed that, as maternal alcohol problems increased, the likelihood of
      adolescent alcohol use increased. Paternal alcohol problems were associated with
      an increased likelihood of alcohol use for girls only. Findings point to the need
      for future research to investigate both maternal and paternal alcohol problems in
      community samples and with a sample size large enough to examine both parent and
      adolescent gender. Implications for preventive and interventive efforts are
      considered.

PMID- 15970395
TI  - Attachment, fear of intimacy and differentiation of self among clients in
      substance disorder treatment facilities.
AB  - Attachment, fear of intimacy and differentiation of self were examined by means
      of self-report questionnaires in 158 volunteers, including 99 clients enrolled in
      addiction treatment programs. As expected, clients (who were undergoing treatment
      for alcoholism, heroin addiction, amphetamine/cocaine addiction or cannabis
      abuse) reported higher levels of insecure attachment and fear of intimacy, and
      lower levels of secure attachment and differentiation of self, compared to
      controls. Insecure attachment, high fear of intimacy and low self-differentiation
      appear to characterize clients enrolled in addiction treatment programs. Such
      characteristics may reflect a predisposition to substance problems, an effect of
      chronic substance problems, or conceivably both.

PMID- 15970396
TI  - Asthma inhaler misuse and substance abuse: a random survey of secondary school
      students.
AB  - PURPOSE: To assess the relationship between prescription asthma inhaler misuse
      and other substance abuse. METHODS: The study included a random sample of 5th
      through 10th grade students attending one, ethnically diverse school district in
      metropolitan Detroit (N=1017). A cross-sectional, web-based survey design was
      used. The survey included questions about the use and misuse of prescribed asthma
      inhalers (among other medications) as well as the use of alcohol, cigarettes,
      marijuana, and other drugs. We investigated four types of interaction with
      prescribed asthma inhalers: non-use, prescribed use, prescribed use and misuse,
      and misuse. RESULTS: Students who misused asthma inhaler medication during their
      lifetimes were more likely to smoke cigarettes and marijuana as well as more
      likely to drink alcohol, binge drink and have used other illicit drugs. Students
      who used asthma inhaler medication solely as prescribed were no more likely to
      abuse drugs or alcohol than non-users of prescription asthma inhalers.
      CONCLUSIONS: Our findings are of interest to clinicians who provide health care
      to adolescents. The present study also has implications for adults managing
      prescription asthma medication in households and schools.

PMID- 15970397
TI  - Sexual orientation and substance use among college students.
AB  - This study examined the relationship between sexual orientation and substance use
      among a nationally representative sample of U.S. college and university students.
      Data from the 1999 College Alcohol Survey were analyzed to compare marijuana and
      other illicit drug use among heterosexual, homosexual, and bisexual students.
      Findings indicate no significant differences in either marijuana or other illicit
      drug use for homosexual students. However, bisexuals, especially females, were
      more likely to have used both marijuana and other illicit drugs. These findings
      underscore the importance of examining bisexuals as a separate group rather than
      combining them together with homosexuals. The findings also indicate the presence
      of unique risk and protective factors based on sexual orientation.

PMID- 15970398
TI  - Licanolide, a new triterpene lactone from Licania tomentosa.
AB  - Licanolide (3beta-hydroxylupane-20,28-olide), a novel triterpene lactone with new
      stereochemical pattern, was isolated from fresh fruits of Licania tomentosa in
      addition to betulinic and palmitoleic acid. The structure elucidation was based
      on spectroscopic methods including two-dimensional NMR experiments (HSQC, HMBC
      and NOESY).

PMID- 15970399
TI  - Identification of core active site residues of the sulfur oxygenase reductase
      from Acidianus ambivalens by site-directed mutagenesis.
AB  - The sulfur oxygenase reductase (SOR) is the initial enzyme in the sulfur
      oxidation pathway of Acidianus ambivalens. The SOR is composed of 308 aa
      residues, three of which are cysteines, and contains a mononuclear non-heme iron
      site. Mutations of the suspected iron-binding residues H86, H90 and E114 to
      alanine resulted in inactive enzyme with no iron incorporated, whereas an E114D
      mutant showed 1% of wild type activity. The mutation of C31 to alanine and serine
      caused inactivity of the enzyme, however, the iron content was the same as in the
      wild type. C101A, C104S/A, and C101/104S/A double mutants caused a decrease in
      specific activity to 10-43% of the wild type while the C101S mutant showed only
      1% activity of the wild type. The drop in activity of the C101S and E114D mutants
      was accompanied with a proportional decrease in iron content. In all cases the
      oxygenase and reductase partial reactions were equally affected. It was concluded
      that the Fe site with H86, H90 and E114 as ligands and C31 constitute the core
      active site whereas C101 and C104 optimize reaction conditions.

PMID- 15970400
TI  - Modulation of the fecal microbiota by the intake of a Lactobacillus johnsonii La1
      containing product in human volunteers.
AB  - Lactobacillus johnsonii La1 (La1) is a probiotic strain capable of stimulating
      the immune system of the host and interfering with gastrointestinal pathogens.
      This study evaluates how the ingestion of different amounts of La1 influences the
      main bacterial populations of the fecal microbiota. Eight asymptomatic volunteers
      participated in the study. After a basal period, they ingested daily 100 mL of a
      product containing 10(8) CFU mL(-1) of La1 during the first week, 200 mL during
      the second week and 500 mL during the third week. Fecal samples were obtained at
      the end of each period and subsequently during 7 weeks. Lactobacilli were
      determined by culture on MRS agar and La1 colonies were confirmed by ERIC-PCR.
      The main populations of fecal bacteria were identified by FISH and flow
      cytometry. At baseline, 37.7% of the total fluorescent bacteria were Eubacterium
      rectale, 18.3% Fusobacterium prausnitzii, 13.2% Bacteroides, 8.6% Atopobium,
      2.30%, Clostridium histolyticum, 2.05% Bifidobacterium and 0.95% Lactobacillus.
      Fecal excretion of La1 increased during the intake period and decreased during
      the post-ingestion period, so that no La1 was observed in the stools of the
      volunteers seven weeks after the intake product has been finished. La1 intake
      increased the populations of C. histolyticum (p=0.049), Lactobacillus (p=0.056)
      and Bifidobacterium (p=0.067), and decreased those of F. prausnitzii (p=0.005)
      while it did not affect Bacteroides, E. rectale and Atopobium populations. These
      bacterial populations returned to their baseline levels during the post-ingestion
      period. The regular intake of a La1-containing product beneficially affects the
      homeostasis of the human fecal microbiota, probably contributing to the health
      promoting effects of this probiotic.

PMID- 15970401
TI  - Increased IRP1 activity in Friedreich ataxia.
AB  - In low-iron conditions, the cytosolic iron-regulatory protein IRP1 binds to iron
      responsive elements (IREs) in mRNAs encoding iron-regulated proteins. In high
      iron conditions, IRP1 incorporates an iron-sulfur cluster (ISC), which interferes
      with IRE binding and prevents intracellular iron accumulation. Here we
      demonstrate an incomplete shift of IRP1 to its ISC form in Friedreich ataxia
      (FRDA) fibroblasts, associated with decreased activities of ISC respiratory
      complexes. Our data suggest an impaired adaptive response to iron accumulation in
      FRDA cells.

PMID- 15970402
TI  - Effects of seropositivity for bovine leukemia virus, bovine viral diarrhoea
      virus, Mycobacterium avium subspecies paratuberculosis, and Neospora caninum on
      culling in dairy cattle in four Canadian provinces.
AB  - The purpose of this research was to determine the effects of seropositivity for
      exposure to bovine leukemia virus (BLV), bovine viral diarrhoea virus (BVDV),
      Mycobacterium avium subspecies paratuberculosis (MAP) and Neospora caninum (NC)
      on overall and reason-specific culling in Canadian dairy cattle. Serum samples
      from, approximately, 30 randomly selected cows from 134 herds were tested for
      antibodies against BLV, MAP and NC using commercially available ELISA test kits,
      while 5 unvaccinated cattle over 6 months of age were tested for antibodies to
      bovine viral diarrhoea virus (BVDV). For analyzing the time (in days) to culling
      of cows after the blood testing, a two-step approach was utilized, non-parametric
      (Kaplan-Meier survival graphs) visualization and then semi-parametric survival
      modelling (Cox proportional hazards model), while controlling for confounding
      variables and adjusting for within herd clustering. For all reasons of culling,
      MAP-seropositive cows had a 1.38 (1.05-1.81, 95% C.I.) times increased hazard of
      culling compared to MAP-seronegative cows. Seropositivity for the other pathogens
      was not associated with an increased risk of overall culling. Among cows that
      were culled because of either decreased reproductive efficiency or decreased milk
      production or mastitis, MAP-seropositive cows were associated with 1.55 (1.12
      2.15, 95% C.I.) times increased hazard compared to MAP-seronegative cows. Among
      cows that were culled because of reproductive inefficiency, NC-seropositive cows
      had a 1.43 (1.15-1.79, 95% C.I.) times greater hazard than NC-seronegative cows.
      Among cows that were culled because of decreased milk production, cows in BVDV
      seropositive herds had a 1.86 (1.28-2.70, 95% C.I.) times increased hazard
      compared to cows in BVDV-seronegative herds. BLV-seropositive cows did not have
      an increased risk of reason-specific culling as compared to BLV-seronegative
      cows. No significant interaction on culling among seropositivity for the
      pathogens was detected, but only a limited number of cows tested seropositive for
      multiple pathogens. Results from our research will help in better understanding
      the economic impacts of these pathogens and justification for their control.

PMID- 15970403
TI  - Putative outer membrane autotransporter protein influences survival of Brucella
      suis in BALB/c mice.
AB  - In Gram-negative bacteria, autotransporters are secreted proteins able to
      translocate themselves through the inner- and outer-membranes to the cell surface
      or to the extracellular environment. The influence of the putative outer membrane
      autotransporter (OmaA) protein to the persistence of Brucella suis was
      investigated. Sequence analyses revealed that the OmaA protein of B. suis strain
      1330 consists of a signal peptide, a passenger alpha-domain, and a transporter
      beta-domain, which are the characteristic components of an autotransporter
      protein. The transporter beta-domain consists of 14 individual amphipathic beta
      strands, and a 46-amino acid long alpha-helix lies upstream of the transporter
      domain, indicating that the B. suis OmaA is a type-I classical autotransporter.
      BLAST search and phylogenetic analyses revealed that the B. suis OmaA protein
      shares more similarities with adhesin autotransporter proteins than with protease
      autotransporter proteins of other bacteria. An OmaA-deficient strain
      (1330DeltaomaA) was generated by disrupting the DNA region encoding the passenger
      alpha-domain of the OmaA protein of B. suis wild type strain 1330. The omaA gene
      encoding the full-length OmaA protein was cloned and used to complement the OmaA
      deficient strain. The OmaA-deficient strain did not differ from the wild type
      strain in terms of persistence in J774 macrophage cell line 24 and 48 h after
      inoculation, or clearance from the spleens of BALB/c mice at 1 week after
      intraperitoneal inoculation. These observations suggest that the function of the
      OmaA protein is dispensable during the acute phase of B. suis infection. However,
      the OmaA-deficient strain was cleared from the spleens of BALB/c mice faster than
      the wild type strain between the third and the ninth week after intraperitoneal
      inoculation, indicating that the OmaA may be important during the chronic phase
      of B. suis infection. Relative to the BALB/c mice injected with saline, those
      vaccinated with the OmaA-deficient strain exhibited 3.0-3.9log10 colony forming
      units protection against a challenge with B. suis strain 1330. This study is the
      first report correlating an autotransporter protein deficiency with persistence
      of B. suis in vitro and in vivo.

PMID- 15970404
TI  - Ultrasound evaluation of the normal fetal pharynx.
AB  - OBJECTIVE: To obtain normative data for fetal pharyngeal diameter and to
      investigate the ability to visualize pharynx at different gestational ages during
      routine prenatal sonography. METHODS: Sonographic studies were performed in 292
      consecutive pregnant women. The diameters of the pharynx were measured and our
      ability to visualize pharynx was evaluated at different gestational ages.
      RESULTS: Sonographic measurements of the pharyngeal diameter were obtained in 153
      of the 292 fetuses. The diameter of the pharynx increased from a mean of 4.5+/
      0.53 mm at 16 weeks to 9.1+/-1.72 mm at 36 weeks. Pharyngeal diameters showed a
      significant positive relationship with advancing gestational age (p<0.0001,
      R2=0.571). The differences in visualization among different gestational age
      groups were found to be significant (p<0.05 by Chi-Square). CONCLUSION: This
      study reports normative data for fetal pharyngeal diameter. Pharyngeal
      measurements were similar to previous reports in the literature. Our success in
      visualizing the pharynx was best between 21 and 30 weeks of gestation. This
      period might be the optimum time for evaluating fetal pharynx.

PMID- 15970405
TI  - Noninvasive measurement of isovolumetric contraction time during hypoxemia and
      acidemia: Fetal lamb validation as an index of cardiac contractility.
AB  - OBJECTIVES: The objectives of this study are firstly to clarify how the Doppler
      isovolumetric contraction time (ICT) is influenced by arterial oxygen pressure
      (PaO2) or pH, and secondly to confirm the relationship between the Doppler ICT
      and myocardial contractility during hypoxemia and/or acidemia in the fetal lamb.
      MATERIAL AND METHODS: In 12 pregnant ewes, fetal hypoxemia and acidemia were
      induced by giving ewes a variable mixture of gases for 120 min. The chronological
      change of fetal PaO2, pH, Doppler ICT and maximum first derivative of the left
      ventricular pressure waveform (Max dp/dt) was recorded every 30 min. RESULTS:
      Doppler ICT and PaO2 had no significant regression. On the other hand, Doppler
      ICT and pH demonstrated a significant negative regression. Moreover, one critical
      given pH point was indicated with statistical significance at 7.20 and the
      prolongation of the Doppler ICT was found more markedly in the range below the pH
      of 7.20 compared with the range above 7.20. A significant negative linear
      regression was found between the Doppler ICT and the Max dp/dt. CONCLUSION: The
      measurement of Doppler ICT enables us to predict severe acidosis and a decrease
      of myocardial contractility in the fetus.

PMID- 15970406
TI  - Quantification of L-type fatty acid binding protein in the urine of preterm
      neonates.
AB  - We measured urinary excretion of L-type fatty acid binding protein (L-FABP) in
      preterm neonates on days 1, 5-10, and 25-30 of life. Urinary L-FABP levels
      (expressed as the ratio to creatinine) in preterm neonates were considerably
      higher than those of healthy adults. They did not change significantly during the
      study period. Urinary L-FABP levels showed significant positive correlation with
      those of urinary N-acetyl-beta-D-glucosaminidase activity on day 1, and with
      those of 8-hydroxy-2'-deoxyguanosine on days 25-30. These results suggest that L
      FABP is expressed in the neonatal kidney. Our results may also point to potential
      effects of proximal tubular damage and oxidative stress on urinary excretion of L
      FABP.

PMID- 15970407
TI  - Using gonadotropin-releasing hormone (GnRH) and GnRH analogs to modulate testis
      function and enhance the productivity of domestic animals.
AB  - Gonadotropin releasing hormone (GnRH) controls the activity of the gonadotrope
      cells of the pituitary gland and, as a consequence, is a critical component of
      the endocrine cascade that determines the growth, development, and functional
      activity of testicular tissue. The use of GnRH and GnRH analogs is common in
      domestic animal production systems. Although GnRH and GnRH analogs are most
      commonly used to control the fertility and reproductive events in female animals,
      GnRH agonists and antagonists are increasingly used to modulate the fertility,
      behavior, and productivity of male animals as well. This review will focus on
      recent advances in this use of GnRH agonists and antagonists.

PMID- 15970408
TI  - Combined surface pressure-interfacial shear rheology studies of the interaction
      of proteins with spread phospholipid monolayers at the air-water interface.
AB  - The adsorption of two model proteins, catalase and lysozyme, to phospholipid
      monolayers spread at the air-water interface has been studied using a combined
      surface pressure-interfacial shear rheology technique. Monolayers of 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3
      [phospho-rac-(1-glycerol)] (DPPG) and DPPC:DPPG (7:3) were spread on a phosphate
      buffer air-water interface at pH 7.4. Protein solutions were introduced to the
      subphase and the resultant changes in surface pressure and interfacial storage
      and loss moduli were recorded with time. The results show that catalase readily
      adsorbs to all the phospholipid monolayers investigated, inducing a transition
      from liquid-like to gel-like rheological behaviour in the process. The changes in
      surface rheology as a result of the adsorption of catalase increase in the order
      DPPC<DPPC:DPPG<DPPG. Lysozyme behaves in a similar manner beneath a DPPG
      monolayer, but shows no measurable differences when injected beneath DPPC or the
      DPPC:DPPG (7:3) mixed monolayer. It is proposed that DPPG monolayers are more
      susceptible to penetration by adsorbing protein molecules. The interaction
      between DPPG and lysozyme is further enhanced due to electrostatic interactions
      between the negatively charged DPPG and the positively charged lysozyme.

PMID- 15970409
TI  - Development of a multi particulate extended release formulation for ZK 811 752, a
      weakly basic drug.
AB  - ZK 811 752, a potent candidate for the treatment of autoimmune diseases,
      demonstrated pH-dependent solubility. The resulting release from conventional
      mini matrix tablets decreased with increasing pH-values of the dissolution
      medium. The aim of this study was to overcome this problem and to achieve pH
      independent drug release. Mini matrix tablets were prepared by direct compression
      of drug, matrix former (polyvinylacetate/polyvinylpyrrolidone; Kollidon SR) and
      excipients (lactose, calcium phosphate or maize starch). To solve the problem of
      pH-dependent solubility fumaric acid was added to the drug-polymer excipient
      system. The addition of fumaric acid was found to maintain low pH-values within
      the mini tablets during release of ZK 811 752 in phosphate buffer pH 6.8. Thus,
      micro environmental conditions for the dissolution of the weakly basic drug were
      kept constant and drug release was demonstrated to be pH-independent.
      Incorporation of water-soluble (lactose) or highly swellable (maize starch)
      excipients accelerated drug release in a more pronounced manner compared to the
      water-insoluble excipient calcium phosphate. Stability studies demonstrated no
      degradation of the drug substance and reproducible drug release patterns for mini
      matrix tablets stored at 25 degrees C/60% RH and 30 degrees C/70% RH for up to 6
      months.

PMID- 15970410
TI  - Effects of an acetone extract of Boswellia carterii Birdw. (Burseraceae) gum
      resin on adjuvant-induced arthritis in lewis rats.
AB  - Ruxiang (Gummi olibanum), the dried gum resin of Boswellia carterii (BC), has
      been used in traditional Chinese medicine to alleviate pain and inflammation for
      thousands of years. In this random, blinded study, the anti-arthritic effects of
      a BC extract were observed and compared to vehicle control in a Lewis rat
      adjuvant arthritis model (n=8/group). Arthritis was induced by injecting CFA
      subcutaneously into the base of the tail, and the extract was administered orally
      (i.g.) for 10 consecutive days beginning on day 16 after the injection. Arthritic
      scores, paw edema, and the local tissue pro-inflammatory cytokines tumor necrosis
      factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) were assessed.
      Toxicity and adverse effects of the extract were evaluated. At 0.90 g/kg per day,
      BC significantly decreased arthritic scores between days 20 and 25 (p<0.05) and
      reduced paw edema on days 18, 20 and 22 compared to control (p<0.05). It also
      significantly suppressed local tissue TNF-alpha and IL-1beta (p<0.05). No major
      adverse effects were observed in animals during the repeated-dose treatment
      profile although mild fur discoloration was noted. The data show that BC extract
      has significant anti-arthritic and anti-inflammation effects and suggest that
      these effects may be mediated via the suppression of pro-inflammatory cytokines.

PMID- 15970411
TI  - Antioxidant activity of Crataegus aronia aqueous extract used in traditional Arab
      medicine in Israel.
AB  - BACKGROUND: The medicinal use of extracts prepared from plant parts of the genus
      Crataegus dates back to ancient times. Furthermore, it has been proposed that its
      antioxidant constituents account for its beneficial therapeutic effects. A
      decoction of leaves and unripe fruits from Crataegus aronia syn. azarolus (L)
      (Rosaceae), the indigenous Israeli hawthorn, is used to treat cardiovascular
      diseases, cancer, diabetes and sexual weakness in Arab traditional medicine.
      PURPOSE: Because laboratory data on the bioactivity of extracts prepared from the
      indigenous Israeli hawthorn is lacking, we evaluated the antioxidant and
      cytotoxic potentials of an extract prepared from leaves and unripe fruits in a
      variety of cell and cell-free in vitro assays. METHODS: The antioxidant assays
      measured: (a) its ability to inhibit (i) oxidation of beta-carotene, (ii) 2,2'
      azobis(2-amidino-propan) dihydrochloride (AAPH)-induced plasma oxidation and
      (iii) iron-induced lipid peroxidation in rat liver homogenates; (b) its ability
      to scavenge the superoxide (O2-) radical; (c) its effects on the enzyme xanthine
      oxidase (XO) activity; (d) its effect on the redox state of glutathione (GSH) in
      cultured Hep G2 cells. In addition, we also evaluated the effects of the extract
      on cell membrane integrity and mitochondrial respiration in cultured Hep G2
      cells. RESULTS AND CONCLUSIONS: Water-soluble extracts inhibited (1) oxidation of
      beta-carotene, (2) AAPH-induced plasma oxidation and (3) Fe(2+)-induced lipid
      peroxidation in rat liver homogenates. In addition, the extract (4) is an
      efficient scavenger of the O2- (5) increases intracellular GSH levels and (6) is
      not cytotoxic. Accordingly, we propose that the therapeutic benefit of Crataegus
      aronia can be, at least in part, attributed to its effective inhibition of
      oxidative processes, efficient scavenging of O2- and possible increasing GSH
      biosynthesis.

PMID- 15970412
TI  - Cerebroprotective effect of Korean ginseng tea against global and focal models of
      ischemia in rats.
AB  - Korean ginseng tea (KGT), prepared from the roots of Panax ginseng, is widely
      used by Korean people for antistress, antifatigue, and endurance promoting
      effects. In the present study we evaluated neuroprotective/cerebroprotective
      actions of KGT in stroke, using rat global and focal models of ischemia. Varied
      biochemical/enzymatic alterations, produced subsequent to the application of
      middle cerebral artery (MCAO) and bilateral carotid artery occlusion (BCAO)
      followed by reperfusion viz. increase in lipid peroxidation (LPO) and decrease in
      glutathione (GSH), glutathione reductase (GR), catalase (CAT), glutathione-S
      transferase (GST), glutathione peroxidase (GPx) and superoxide dismutase (SOD),
      were markedly reversed and restored to near normal levels in the groups pre
      treated with KGT (350 mg/kg given orally for 10 days). It is concluded that the
      protective action, exhibited by KGT against hypoperfusion/reperfusion induced
      brain injury, suggests its therapeutic potential in cerebrovascular diseases
      (CVD) including stroke. These findings are important because: (a) the present
      treatment strategies for CVD are far from adequate and (b) KGT with wide usage is
      known to be a safe natural product.

PMID- 15970413
TI  - Cellular senescence in vivo: its relevance in ageing and cardiovascular disease.
AB  - In most somatic mammalian cell types extensive replication and various types of
      cellular insults induce a permanent form of growth arrest called senescence.
      Senescence has been comprehensively characterised in cell culture, but its
      occurrence in vivo has only recently started to become appreciated. In this mini
      review, we examine the evidence for the occurrence of senescence in vivo, with
      particular emphasis on the cardiovascular system. We also describe the senescent
      phenotype and discuss its pathophysiological implications. We examine findings in
      animal models of ageing and human genetic disorders that argue for and against a
      role of senescence in age-related pathologies in general and vascular disease in
      particular.

PMID- 15970414
TI  - Aging and Gi smooth muscle fecal incontinence: Is bioengineering an option.

PMID- 15970415
TI  - Preservation of heat stress induced myocardial hsp 72 in aged animals following
      caloric restriction.
AB  - The major stress inducible Heat Shock Protein (HSP 72) confers myocardial
      protection from ischemia. A decreased ability to express HSP 72 during
      homeostatic disruptions has been suggested as a possible mechanism for the
      increased susceptibility of aged hearts to ischemic stress. Given that Caloric
      Restriction (CR) has been reported to reverse or delay age-associated cellular
      senescence, we examined the effect of CR on the ability of aged hearts to induce
      and accumulate HSP 72. Adult (6 months), aged (22 months) and CR aged (22 months)
      Fisher 344 rats were heat stressed by raising core temperature to 41 degrees C
      for 10 min. Immediately after heat stress, or 24 h later, the myocardium was
      examined for either activation of the heat shock transcription factor (HSF) or
      HSP 72 accumulation. Hearts from heat stressed CR animals demonstrated an
      increased HSF activation and an increased HSP 72 content when compared to hearts
      from heat stressed aged animals. The HSF response and HSP 72 content of the
      hearts from heat stressed aged CR animals was comparable to that observed in
      hearts from heat stressed adult animals. These results suggest CR may preserve
      the ability of the aged myocardium to activate and/or express HSP 72.

PMID- 15970416
TI  - Color Doppler sonographic findings in focal spleen lesions.
AB  - Since focal lesions of the spleen are rare (0.2%), there is little data
      concerning color Doppler images of focal lesions of the spleen. OBJECTIVE: The
      aim of this study is to describe the color Doppler images of 98 etiologically
      proved focal spleen lesions. METHODS: In about 110,000 consecutive abdominal
      ultrasound examinations, which included the spleen, 600 patients with focal
      lesions of the spleen were identified. In 98 of these patients a color Doppler
      scan of the lesion was performed and documented. These scans were analysed
      retrospectively and classified as avascular, hypovascular, isovascular,
      hypervascular and arterio-venous "high flow", using the surrounding spleen tissue
      as an in vivo reference. RESULTS: In color Doppler sonography (CDS) 68.4% (n=67)
      of the focal spleen lesions showed no flow. 15.3% (n=15) appeared hypovascular,
      8.2% (n=8) isovascular, 5.1% (n=5) hypervascular, and in 3.1% (n=3) an arterio
      venous "high flow"-pattern was found. CONCLUSIONS: In CDS about two thirds (68%)
      of focal spleen lesions appear to be avascular. Except from diagnosis of intra
      splenic pseudo-aneurysm, the practical utility of CDS in diagnosing focal spleen
      lesions has to be estimated as low.

PMID- 15970417
TI  - Simultaneous determination of rosuvastatin and fenofibric acid in human plasma by
      LC-MS/MS with electrospray ionization: assay development, validation and
      application to a clinical study.
AB  - A simple, sensitive and specific LC-MS/MS method for simultaneous determination
      of rosuvastatin (RST) and fenofibric acid (FFA) was developed and validated with
      500 microL human plasma using carbamazepine as an internal standard (IS). The
      assay procedure involved a simple one-step liquid/liquid extraction of RST and
      FFA and IS from plasma into ethyl acetate. The organic layer was separated and
      evaporated under a gentle stream of nitrogen at 40 degrees C. The residue was
      reconstituted in the mobile phase and injected onto X-Terra MS C-18 column (4.6
      mm x 50 mm, 5.0 microm). Separation of RST, FFA and IS was achieved with a mobile
      phase consisting of 0.05 M formic acid:acetonitrile (45:55, v/v) at a flow rate
      of 0.40 ml/min. The API-3000LC-MS/MS was operated under the multiple reaction
      monitoring mode (MRM) using the electrospray ionization technique. Positive ion
      acquisition chromatographic run was used in the present method. Nominal retention
      times of RST, FFA and IS were 2.35, 4.70 and 2.32 min, respectively. Absolute
      recovery of RST, FFA and IS was 74, 61 and 69%, respectively. The lower limit of
      quantification (LLOQ) of RST and FFA was 1.00 ng/ml and 0.50 microg/ml,
      respectively. Response function was established for the range of concentrations
      1.00-50.0 ng/ml and 0.50-20.0 microg/ml for RST and FFA, respectively, with a
      coefficient of determination (r2) of 0.999 for both the compounds. The inter- and
      intra-day precision in the measurement of RST quality control (QC) samples 5, 15,
      400 and 800 ng/ml, were in the range 8.93-9.37% relative standard deviation
      (R.S.D.) and 1.74-16.1% R.S.D., respectively. Similarly, the inter- and intra-day
      precision in the measurement of FFA quality control (QC) samples 0.5, 1.5, 8.0
      and 15.0 microg/ml, were in the range 9.78-11.6% relative standard deviation
      (R.S.D.) and 0.22-17.4% R.S.D., respectively. Accuracy in the measurement of QC
      samples for RST and FFA were in the range 88.1-108 and 87-115%, respectively, of
      the nominal values. RST and FFA were stable in the battery of stability studies,
      viz., bench-top, auto-sampler and freeze/thaw cycles. Stability of RST and FFA
      was established for 1 month at -80 degrees C. The application of the assay to a
      clinical study confirmed the utility of the assay.

PMID- 15970418
TI  - Simultaneous determination of HIV-protease inhibitors lamivudine and zidovudine
      in pharmaceutical formulations by micellar electrokinetic chromatography.
AB  - A micellar electrokinetic chromatographic (MEKC) method for the simultaneous
      separation and determination of lamivudine (LMV) and zidovudine (ZDV) in
      pharmaceutical formulation has been developed. Factors that affect the
      separation, such as buffer pH, surfactant concentration (sodium dodecyl sulfate,
      SDS), organic solvents and applied voltage were optimized. Buffer consisting of
      12.5 mM sodium tetraborate decahydrate and 15 mM boric acid adjusted at pH 10.8,
      containing 90 mM SDS and 5% (v/v) acetonitrile (ACN) was found to be suitable for
      the separation of the drugs. p-Aminobenzoic acid (PABA) was used as internal
      standard (I.S.). Detection of analytes and I.S. was performed at a wavelength of
      210 nm. It was observed that both the drugs and I.S. were migrated within 20 min
      at the applied voltage of +10 kV. Validation of the method was performed in terms
      of linearity, accuracy, precision, limit of detection (LOD) and quantification
      (LOQ). An excellent linearity was obtained in the concentration range 10-80
      microg/ml for LMV and 10-100 microg/ml for ZDV. The detection limits for LMV and
      ZDV were found to be 2.5 and 2.0 microg/ml, respectively. The optimized method
      was applied to the simultaneous determination of LMV and ZDV in pharmaceutical
      formulation and human plasma (spiked) samples. Recovery of both the drugs in
      tablet dosage form and spiked drugs in plasma were > or =99.72% (relative
      standard deviation (R.S.D.)< or =1.84%) and > or =80.4% (R.S.D.< or =5.4%),
      respectively. In the electropherogram no interfering peaks were observed in the
      region of analytes and I.S. due to inactive ingredients in the tablets and
      matrices in plasma.

PMID- 15970419
TI  - Endolymphatic potassium of the chicken vestibule during embryonic development.
AB  - The endolymph fills the lumen of the inner ear membranous labyrinth. Its ionic
      composition is unique in vertebrates as an extracellular fluid for its high
      K(+)/low-Na(+) concentration. The endolymph is actively secreted by specialized
      cells located in the vestibular and cochlear epithelia. We have investigated the
      early phases of endolymph secretion by measuring the endolymphatic K(+)
      concentration in the chicken vestibular system during pre-hatching development.
      Measurements were done by inserting K(+)-selective microelectrodes in chicken
      embryo ampullae dissected at different developmental stages from embryonic day 9
      up to embryonic day 21 (day of hatching). We found that the K(+) concentration is
      low (<10mM/L) up to embryonic day 11, afterward it increases steeply to reach a
      plateau level of about 140 mM/L at embryonic day 19--21. We have developed a
      short-term in vitro model of endolymph secretion by culturing vestibular ampullae
      dissected from embryonic day 11 chicken embryos for a few days. The preparation
      reproduced a double compartment system where the luminal K(+) concentration
      increased along with the days of culturing. This model could be important for (1)
      investigating the development of cellular mechanisms contributing to endolymph
      homeostasis and (2) testing compounds that influence those mechanisms.

PMID- 15970420
TI  - An evaluation of the Decisional Conflict Scale for measuring the quality of end
      of-life decision making.
AB  - OBJECTIVE: Researchers and clinicians acknowledge the complexity of planning for
      future medical treatment desired in the event of incapacitation. Unfortunately,
      many attempts to evaluate the quality of such difficult planning have been
      stymied by the lack of measures that can be shown to have validity. This study
      examines the psychometric characteristics of the Decisional Conflict Scale (DCS)
      when used as a measure of patients' evaluation of their end-of-life decision
      making process. METHODS: This evaluation used the combined data from two
      independent samples in which 59 outpatients with a life-threatening illness and
      their surrogate decision makers were assigned to receive, a decision aid
      intervention, the patient-centered advance care planning (PcACP), or usual care
      only. RESULTS: Internal consistency for the DCS in the end-of-life decision
      making context was high. The DCS demonstrated convergent, construct, and
      discriminant validity based on the total scale scores. CONCLUSION: The DCS
      appears to be a viable research instrument for measuring the quality of end-of
      life decision making. However, the uncertainty subscale showed a weak
      discriminating ability and lack of association with the two other subscales, the
      modifiable factors contributing to uncertainty and the effectiveness of the
      decision making. PRACTICE IMPLICATIONS: The findings of the study can be useful
      for measuring decisional conflict in individuals with serious illness facing end
      of-life decision making.

PMID- 15970421
TI  - "Tu" or "Vous?" A European qualitative study of dignity and communication with
      older people in health and social care settings.
AB  - OBJECTIVE: To examine the experiences of communication between older people and
      health and social care providers in six European countries. METHODS: Focus groups
      were carried out with groups of older people (91 focus groups, 391 participants),
      and health and social care professionals (85 focus groups, 424 participants), in
      order to gain insights into concepts of good communications. Data collection and
      analysis continued concurrently according to the method of constant comparison.
      RESULTS: Different styles of communication between professionals and older people
      were found to be capable of enhancing or jeopardising dignity. The use of
      appropriate forms of address, listening, giving people choice, including them,
      respecting their need for privacy and politeness, and making them feel valued
      emerged as significant ways to maintain older peoples' sense of self-worth and
      dignity. Despite being aware of good communication practices, health and social
      care professionals often failed to implement them. Lack of time, staff, resource
      scarcity, regulation and bureaucracy were cited as barriers, as was a lack of
      awareness and effort. CONCLUSIONS AND PRACTICE IMPLICATIONS: The findings have
      important implications for health and social care professionals when they engage
      with older people.

PMID- 15970422
TI  - Does physician-patient communication that aims at empowering patients improve
      clinical outcome? A case study.
AB  - OBJECTIVE: A case study at the department for heart surgery of an Austrian
      University Hospital in 2001, examined the outcome of improved communication aimed
      at empowering patients to be more effective co-producers of recuperation after
      surgery. METHODS: Evaluated were the effects of a training program for developing
      communication skills of health professionals (physicians, physiotherapists, and
      nurses) along with a reorganization of patient information schemes. The clinical
      outcomes after four types of surgery (bypass, stent, artificial valve insertion
      and combination of these) were observed in 100 patients without (control group)
      and 99 with the intervention administered (intervention group). Two objective and
      two subjective health outcome parameters were selected for analysis: care level
      adjusted length of stay in hospital, frequency of post-surgery complications,
      subjective health, subjective satisfaction with care received. Self-administered
      breathing exercises were measured as an intermediary outcome parameter. RESULTS:
      In the intervention group length of hospital stay was shorter (by 1 day),
      incidence of post-surgery tachyarrhythmia was reduced (by 15%), transfer to less
      intensive care levels was faster and patient ratings for communicative quality of
      care by doctors and nurses were improved. CONCLUSION: Professional communication
      aimed at empowering patients to act as co producers can indeed have an effect on
      clinical outcome. PRACTICE IMPLICATIONS: Staff training and reorganization of
      communication schemes can be an effective intervention in hospital care.

PMID- 15970423
TI  - Polymorphisms of 5' flanking region of chicken prolactin gene.
AB  - The polymorphisms of 5' flanking region of chicken prolactin (cPRL) gene were
      examined in several populations of Chinese native Yuehuang, Taihe Silkie and
      imported White Leghorn Layer chickens. The 5' flanking regions (2638 bp) from
      Yuehuang, Taihe Silkie and White Leghorn chickens were subjected to sequencing
      analysis. Four single nucleotide polymorphisms (SNPs) were identified at position
      -2425(C/T), -2215(T/C), -2063(G/A) and -1967(A/G). A 24-bp indel (insertion or
      deletion) and a polyA length polymorphism were also identified. For the 24-bp
      indel locus, three genotypes (AA, AB and BB) were found in Yuehuang chickens,
      while only two genotypes were detected in Taihe Silkie (AB and BB) and Leghorn
      chickens (AA and BB). The genotype frequencies of AA, AB and BB were
      significantly different among the three breeds. For the polyA locus, although
      three genotypes (CC, CD and DD) were found, only one genotype (CC) was detected
      in White Leghorn chickens, while two or three genotypes were observed in Chinese
      native chickens. We used real-time quantitative PCR and radioimmunology assay to
      investigate the potential association of the 24-bp indel locus with cPRL mRNA
      expression, plasma cPRL and brooding behaviors, and observed that chickens with
      genotype AB, which are of the highest incidence of broodiness, had the highest
      cPRL mRNA levels, providing the possibility that this polymorphic site might be
      related to the broodiness in chickens via modulating the transcriptional level of
      cPRL gene. The dissociation among cPRL gene transcription, mRNA storage and
      hormone release was also observed.

PMID- 15970424
TI  - Lectin reactivity of expanded mouse blastocysts after exposure to sera from women
      with unexplained recurrent spontaneous abortion.
AB  - Embryotoxic factors existing in maternal sera may influence their effects via
      specific binding to, or alteration of cell surface molecules in the conceptus.
      This study was undertaken to determine the effects of sera from women with
      unexplained recurrent spontaneous abortion (URSA) on cell surface glycoconjugates
      of the early conceptus. Four cell stage embryos were cultured in medium
      supplemented with sera from women with URSA, from normal women, or in medium
      without serum. Developmental competence was assessed as the stage distribution of
      embryos advancing to during 96h in culture. Hatched (expanded) blastocysts were
      stained with wheat germ agglutinin (WGA), peanut agglutinin (PNA) and dolichos
      biflorus agglutinin (DBA) to detect surface glucoconjugates. We observed that
      patient sera could be divided into high- and low-risk groups on the basis of the
      ability to decrease the number of four-cell embryos reaching the expanded
      blastocyst stage. Furthermore, the intensity of reactivity to PNA changed after
      exposure to high-risk sera. Morula formation was reduced and blastocyst formation
      was delayed. Although the sera from women with URSA had embryotoxic effects, no
      influence on the glycoconjugate patterns were evident in hatched blastocysts,
      aside from PNA reactivivity. We suggest altered developmental display of PNA
      reactive proteins was a biomarker for poor developmental quality due to
      emrbyotoxic factors in serum from URSA patients.

PMID- 15970425
TI  - In response to Commentary by Gary Kimmel, Stephen Harris, Melissa Tassinari,
      Thomas Knudsen, Helen Cunny, Rochelle Tyl, Betsy Carlton, Joseph Holson and
      William Slikker Reprod Toxicol. September-October 2004;18(5):623-24.

PMID- 15970426
TI  - Programmed Instruction to teach pointing with a computer mouse in preschoolers
      with developmental disabilities.
AB  - Programmed Instruction combined with experimenter-provided prompts (physical,
      verbal, and gesturing) was used to teach pointing with a computer mouse. Three
      preschoolers who scored at least 1 year below their chronological age levels
      participated. During the pre-assessment, none of the participants demonstrated
      pointing. However, they could press and release the mouse button. Programmed
      Instruction consisted of three stages, based on an analysis of the behavioral
      prerequisites for pointing. Stage 1 was designed to teach participants to move
      the mouse. Stage 2 was designed to teach participants to move the on-screen
      cursor onto specific items on the screen. Stage 3 was designed to teach
      participants to click on specific items on the screen. Experimenter-provided
      prompts were used to facilitate skill acquisition at each stage. The post
      assessment showed that all participants learned pointing after intervention. The
      intervention package consisting of Programmed Instruction and experimenter
      provided prompts was effective for teaching the hand-eye coordination required
      for pointing.

PMID- 15970428
TI  - Differential involvement of the integrin-linked kinase (ILK) in RhoA-dependent
      rearrangement of F-actin fibers and induction of connective tissue growth factor
      (CTGF).
AB  - The integrin-linked kinase (ILK) serves as an adapter protein to link the
      cytoplasmic domains of integrins with cytoskeletal components. Organization of
      the actin cytoskeleton is strongly influenced by the small GTPase RhoA, which
      also regulates gene expression. To investigate the impact of ILK deficiency on
      RhoA-mediated signaling we used ILK-deficient fibroblasts. The cytoskeleton of
      ILK (-/-) cells was characterized by less organized F-actin fibers, compared to
      wild type mouse fibroblasts. Stimulation of the cells with lysophosphatidic acid
      (LPA) or the microtubule disrupting agent colchicine increased polymerization of
      F-actin stress fibers in ILK (+/+) cells, whereas ILK (-/-) cells showed a
      network of short thin cortical actin fibers, cell rounding and finally detachment
      from the surface of the culture plates. The structural changes were primarily
      attributable to the activation of RhoA in both cell types. ILK deficiency also
      affected gene expression. The basal levels of several proteins related to
      fibroblast differentiation, such as connective tissue growth factor (CTGF),
      thrombospondin 1 and alpha smooth muscle actin, were reduced in ILK (-/-) cells.
      However, induction of CTGF expression by LPA or colchicine was comparable in ILK
      (+/+) and ILK (-/-) cells. Furthermore, stimulation of CTGF or thrombospondin by
      TGFbeta was not reduced by ILK deficiency. Inhibition of the RhoA-associated
      kinase or overexpression of dominant negative RhoA reduced the stimulated CTGF
      expression indicative of a role for RhoA signaling in CTGF expression. Taken
      together, ILK is involved in RhoA-dependent reorganization of the actin
      cytoskeleton, whereas activation of RhoA and RhoA-mediated gene expression is
      independent of ILK.

PMID- 15970427
TI  - The anti-apoptotic effect of leukotriene B4 in neutrophils: a role for
      phosphatidylinositol 3-kinase, extracellular signal-regulated kinase and Mcl-1.
AB  - The constitutive commitment of neutrophils to apoptosis is a key process for the
      control and resolution of inflammation and it can be delayed by various
      inflammatory mediators including leukotriene B4 (LTB4). The mechanisms by which
      LTB4 contributes to neutrophil survival are still unclear and the present work
      aims at identifying intracellular pathways underlying this effect. Inhibition of
      human neutrophil apoptosis by LTB4 was abrogated by the phosphatidylinositol 3
      kinase (PI3-K) inhibitor wortmannin and by the specific MEK inhibitor PD98059. In
      contrast, inhibitors of p38 MAPK, Jak2/3 and Src did not hinder the anti
      apoptotic effect of LTB4. We also investigated the effects of members of the Bcl
      2 family as they play a crucial role in the regulation of programmed cell death.
      When neutrophils were incubated with LTB4 for 1 to 6 h, the mRNA levels of the
      anti-apoptotic protein Mcl-1 were upregulated approximately 2-fold, while those
      of the pro-apoptotic protein Bax were downregulated 3- to 4-fold, as determined
      by real-time PCR. Accordingly, Western blot analysis revealed that the expression
      of Mcl-1 was upregulated in presence of LTB4, while flow cytometric analysis
      revealed that Bax protein was downregulated. Furthermore, the modulatory effects
      of LTB4 on Mcl-1 and Bax proteins were abolished in the presence of either
      wortmannin or PD98059. Taken together, these results demonstrate the
      participation of PI3-K and MEK/ERK kinases, as well as regulatory apoptotic
      proteins such as Mcl-1 and Bax, in the anti-apoptotic effects of LTB4 in human
      neutrophils.

PMID- 15970430
TI  - CD40 mediated human cholangiocyte apoptosis requires JAK2 dependent activation of
      STAT3 in addition to activation of JNK1/2 and ERK1/2.
AB  - CD40 is critically involved in Fas-mediated cholangiocyte apoptosis during liver
      inflammation, but the underlying signalling events are poorly understood. Our
      recent work implicated AP-1 in CD40-induced cholangiocyte apoptosis, but
      suggested involvement of other signalling pathways. Because STAT3 has been
      implicated in liver regeneration we investigated this signalling pathway during
      CD40 mediated cholangiocyte apoptosis. Western immunoblotting, electrophoretic
      mobility gel shift assays, In situ DNA end labelling and caspase-3 activity were
      used to investigate intracellular signalling and apoptosis in primary human
      cholangiocytes following CD40 activation. CD40-activation induced caspase-3
      dependent cholangiocyte apoptosis and 3-fold increases in JNK/ERK phosphorylation
      (concomitant with increased AP-1 binding activity) and 4-fold increases in
      pSTAT3, which were sustained for up to 24 h. Protein levels of c-Jun, c-Fos and
      pSTAT3 confirmed the upregulation. Phosphorylation of p38 remained unchanged
      suggesting that this MAP kinase was not involved in CD40 mediated apoptosis.
      Increased JAK2 phosphorylation accompanied increased STAT3 phosphorylation after
      CD40 ligation. Cholangiocytes were also shown to express JAK1 and 3 which was
      phosphorylated following control stimulation with TNFalpha or IL2 respectively
      but not after CD40 ligation. JNK, ERK and JAK2 inhibitors partially abrogated
      apoptosis and when used in combination reduced it to basal levels. In conclusion,
      induction of CD40-mediated cholangiocyte apoptosis requires JAK2-mediated
      phosphorylation of STAT3 as well as sustained JNK1/2, ERK1/2 activation. This
      study demonstrates that STAT3 can function as a proapoptotic factor in primary
      human liver epithelial cells.

PMID- 15970429
TI  - High glucose-induced apoptosis in human vascular endothelial cells is mediated
      through NF-kappaB and c-Jun NH2-terminal kinase pathway and prevented by
      PI3K/Akt/eNOS pathway.
AB  - Our previous studies demonstrated that high glucose-induced apoptosis in human
      umbilical vein endothelial cells (HUVECs) is mediated by sequential activation of
      c-Jun N-terminal kinase (JNK) and caspase, and prevented by exogenous nitric
      oxide (NO). In this study we further elucidated the roles of the transcriptional
      factor NF-kappaB, phosphatidylinositol 3'-kinase (PI3K), Akt and endothelial
      nitric oxide synthase (eNOS) in the apoptosis of HUVECs induced by high glucose.
      The results showed that high glucose-induced apoptosis was significantly enhanced
      by PI3K inhibitors (wortmannin and LY294002), NOS inhibitor (NG-nitro-arginine
      methyl ester) and eNOS antisense oligonucleotide. In contrast, apoptosis was
      markedly reduced by NF-kappaB inhibitor (pyrrolidine dithiocarbamate, PDTC), NF
      kappaB antisense oligonucleotide, NO donor (sodium nitroprusside, SNP), and
      overexpression of Akt. The high glucose-induced NF-kappaB activation and
      transient Akt phosphorylation were prevented by the presence of vitamin C.
      Moreover, high glucose-induced increase in eNOS expression was attenuated by PI3K
      inhibitors and the negative mutant of PI3K. The activity of JNK induced by high
      glucose was suppressed by NF-kappaB-specific antisense oligonucleotide. Taken
      together our results demonstrated that high glucose-induced HUVECs apoptosis is
      through NF-kappaB-dependent JNK activation and reactive oxygen species (ROS)
      dependent Akt dephosphorylation. Activation of the ROS/PI3K/Akt/eNOS signaling
      pathway in early phase exerts protective effects against the induction of
      apoptosis by high glucose.

PMID- 15970431
TI  - No association of haplotype-tagging SNPs in TRAR4 with schizophrenia in Japanese
      patients.
AB  - Recent study of linkage disequilibrium mapping showed one of the trace amine
      receptor (TRAR) genes, TRAR4, was associated with schizophrenia. We conducted a
      replication study of TRAR4 with schizophrenia in Japanese patients. We used two
      large independent sets of samples in a first-set analysis (cases=405,
      controls=401) and second-set analysis (cases=503, controls=440). In the first-set
      analysis, one Marker (Marker5) showed a significant association, but this
      significance was not seen in the second-set analysis. Our results indicate that
      TRAR4 may not play a major role in Japanese schizophrenia patients, and that it
      is important to examine the possibility of false positives in genetic association
      analysis.

PMID- 15970432
TI  - Prevalence of resistant Pseudomonas aeruginosa with elective and rescue
      intravenous antibiotic regimens in children with cystic fibrosis.

PMID- 15970433
TI  - The role of antibiotics in chronic bacterial prostatitis.
AB  - The role of antibiotic treatment in prostatitis is described. The selection of an
      appropriate antimicrobial agent with optimal pharmacokinetics for prostatic
      secretion and tissue is important, particularly in chronic bacterial prostatitis
      (CBP). The theoretical background of drug penetration into the prostate is
      outlined, emphasising the phenomenon of ion trapping and the role of non-ionic
      diffusion of weak acids, bases and amphoteric drugs across biological membranes
      with a pH gradient. Determination of drug concentrations in human prostatic
      secretion is problematic because of possible urinary contamination. Studies have
      been carried out mainly in healthy volunteers. The results must be interpreted
      with caution if no care was taken to rule out or at least to identify urinary
      contamination. Analysing the concentrations of various fluoroquinolones in
      prostatic and seminal fluid as well as in prostatic tissue, it becomes obvious
      that the fluoroquinolones differ not only in plasma concentrations but also in
      their penetration to these sites. In spite of intensive investigations, our
      knowledge is still limited regarding the mechanisms that govern the transport of
      antibiotics into and their activity in the various prostatic compartments and how
      these findings can be applied clinically. Nevertheless, the concentrations at the
      site of infection of most of the fluoroquinolones should be sufficient for the
      treatment of CBP and vesiculitis caused by susceptible pathogens.

PMID- 15970434
TI  - A functional MRI comparison of patients with obsessive-compulsive disorder and
      normal controls during a Chinese character Stroop task.
AB  - Recent functional neuroimaging and neuropsychological studies have suggested that
      abnormal activity in the anterior cingulate cortex (ACC) might cause an action
      monitoring dysfunction in obsessive-compulsive disorder (OCD). To identify the
      relationship between brain dysfunction and cognitive dysfunction, we examined
      regional brain changes in OCD with functional magnetic resonance imaging (fMRI)
      during the performance of a cognitive task. Participants comprised 24 patients
      with OCD and 14 normal controls. First, we compared the cognitive function in the
      two groups as assessed by several neuropsychological tests. Then we used fMRI to
      explore brain correlates of their performance during the Chinese character
      version of the Stroop test, a task that is strongly related to action-monitoring
      function. The two groups did not differ on the neuropsychological tests. Both
      groups also showed similar activation pattern on fMRI. The patients, however,
      showed weaker activation than the normal controls in the ACC and the right
      caudate nucleus.

PMID- 15970435
TI  - Intranasal delivery of recombinant human growth hormone (somatropin) in sheep
      using chitosan-based powder formulations.
AB  - The effectiveness of chitosan in promoting the intranasal bioavailability of
      recombinant human growth hormone (hGH) has been evaluated. hGH was formulated
      with chitosan to produce a powder blend (Formulation A) and granules (Formulation
      B) for intranasal administration. The in vivo pharmacokinetic performance of the
      formulations was evaluated in a group of six sheep in a randomised crossover
      study. A subcutaneous injection of hGH solution was administered as a control.
      The intranasal and subcutaneous doses of hGH were 0.3 and 0.03 mg/kg,
      respectively. The intranasal formulations appeared to be well tolerated. Mean
      bioavailabilities of hGH from Formulations A and B were 14 and 15%, respectively
      relative to subcutaneous injection. It is concluded that chitosan-based
      intranasal powder formulations may provide a practical means for non-injectable
      delivery of hGH and, potentially, other therapeutic protein molecules.

PMID- 15970436
TI  - Insect cell conditioned medium contains an endoglycosidase able to liberate
      chondroitin sulfate chains from aggrecan.
AB  - Culture medium obtained from baculovirus-infected High Five insect cells contains
      an endoglycosidase activity capable of releasing chondroitin sulfate chains from
      aggrecan, decorin and biglycan. Release appears to occur by cleavage within the
      linkage region of the chondroitin sulfate chain, but not all chains are amenable
      to release. Culture medium from Sf9 insect cells does not contain this activity.
      The endoglycosidase may become a useful reagent for biochemical research for
      releasing intact chondroitin sulfate chains from proteoglycans. It may also
      represent an impediment to such research when baculovirus systems are used to
      generate recombinant proteoglycans.

PMID- 15970437
TI  - Tissue- and bone cell-specific expression of bone sialoprotein is directed by a
      9.0 kb promoter in transgenic mice.
AB  - Bone sialoprotein (BSP) is a phosphorylated glycoprotein that is expressed almost
      exclusively in mineralizing connective tissues. In bone, expression of BSP
      correlates with the differentiation of osteoblasts and the onset of
      mineralization. To determine how the tissue- and differentiation-specific
      transcription of BSP is regulated, various lengths of promoter sequence were
      ligated to a luciferase reporter and stably transfected into a rat stromal bone
      marrow cell line, RBMC-D8 and undifferentiated C3H10T1/2 cells. Luciferase
      transcription of reporter constructs including 5.4 kb (mBSP5.4Luc) and 9.0 kb
      (mBSP9.0Luc) of the BSP promoter was strongly up-regulated in parallel with
      endogenous BSP mRNA in differentiating SBMCs, but not in C3H10T1/2 cells. In
      contrast, 0.1 kb and 1.4 kb BSP promoter constructs did not show selective
      expression. To determine tissue-specific expression in vivo, transgenic mice
      expressing reporter constructs for the 9.0 kb promoter and a 4.8 kb promoter
      lacking two upstream Cbfa1/Runx2 elements (mBSP9.0Luc and mBSP4.8Luc,
      respectively) were generated. Analysis of various tissues collected from 1-, 4-,
      7-, 14-, and 42-day-old mice revealed extremely high levels of luciferase
      activity in calvaria, mandible, and tibia of the mBSP9.0Luc mice. In contrast,
      soft tissues showed negligible luciferase expression. Mice harboring the 4.8 kb
      transgene also showed selective luciferase expression but displayed a
      significantly lower activity in mineralized tissues. Northern hybridization of
      endogenous BSP mRNA and immunostaining of BSP in mBSP9.0Luc mice showed a temporo
      spatial expression pattern consistent with the luciferase activity. These results
      indicate that regulatory elements within the 9.0 kb region of the promoter are
      required for strong, tissue- and differentiation-specific expression of BSP.

PMID- 15970438
TI  - Electrochemical mutagen screening using microbial chip.
AB  - Electrochemical microbial chip for mutagen screening were microfabricated and
      characterized by scanning electrochemical microscopy (SECM). Salmonella
      typhimurium TA1535 with a plasmid pSK1002 carrying a umuC'-'lacZ fusion gene was
      used for the whole cell mutagen sensor. The TA1535/pSK1002 cells were exposed to
      mutagen solutions containing 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamido (AF-2),
      mitomycin C (MMC) or 2-aminoanthracene (2-AA) and embedded in a microcavity (5nl)
      on a glass substrate using collagen gel. The beta-galactosidase expression on the
      microbial chip was electrochemically monitored using p-aminophenyl-beta-d
      galactopyranoside (PAPG) as the enzymatic substrate. This system has several
      advantages compared with the conventional umu test: drastic reduction of the
      sample volume, less time-consuming for beta-galactosidase detection (free from
      substrate reaction time) and lower detection limit for the three mutagens (AF-2,
      MMC, 2-AA). Finally, a multi-sample assay was carried out using the microbial
      array chip with four microcavities.

PMID- 15970439
TI  - Long-term effects of aromatase inhibitors on bone.
AB  - The risk of fracture in the postmenopausal woman given aromatase inhibitors may
      be increased by up to 60%. This is likely to be true for all third generation
      drugs, but the clinical trials did not include sufficient fracture events for
      certainty on this issue. It would appear that most of the excess fracture risk
      relates to vertebral fracture and in future studies, more effort should be given
      to ascertaining these fractures. The likely mechanism for the increase in
      fracture risk is an increase in bone turnover (of about 20%) and an acceleration
      of bone loss. There is evidence to suggest that the residual levels of oestradiol
      present in the postmenopausal woman are important for bone health, and thus, the
      effect of these drugs is to remove this protective effect. Current clinical
      practice should include the measurement of bone mineral density in postmenopausal
      women taking these drugs and commencement of antiresorptive therapy if
      osteoporosis is already present.

PMID- 15970440
TI  - Genistein restricts leptin secretion from rat adipocytes.
AB  - The isoflavones--genistein and daidzein -- compounds found in high concentrations
      in soy play an important role in prevention of many diseases and affect some
      metabolic pathways. In the performed experiment it was demonstrated that
      genistein (5mg/kg b.w.) administered intragastrically for three days to male
      Wistar rats substantially diminished blood leptin level. Studies with isolated
      rat adipocytes revealed that this phytoestrogen strongly restricted leptin
      secretion from these cells. These effects were not accompanied by any changes in
      leptin gene expression in adipocytes. Daidzein-- an analogue of genistein -- used
      at similar concentrations did not affect blood leptin concentration, leptin
      secretion and expression of its gene. To determine the influence of genistein and
      daidzein on leptin release, adipocytes isolated from the epididymal fat tissue
      were incubated for 2h in Krebs--Ringer buffer. Leptin secretion stimulated by
      glucose with insulin was significantly diminished by genistein (0.25--1mM). This
      effect of genistein may arise from several aspects of its action in adipocytes
      documented in the literature such as the inhibition of glucose transport and
      metabolism, the attenuation of insulin signalling, the inhibition of cAMP
      phosphodiesterase and the stimulation of lipolysis. However, the bypassing of the
      restrictive action of genistein on glucose transport and glycolysis (by the use
      of alanine instead of glucose) and on insulin action (by the use of nicotinic
      acid) was not sufficient to restore leptin secretion from isolated adipocytes. It
      was also demonstrated that the restriction of the stimulatory influence of
      genistein on cAMP/protein kinase A (PKA) pathway (by the inhibition of PKA
      activity) did not improve leptin release. Results obtained in our experiments
      point at the restriction of glucose metabolism following formation of pyruvate as
      the pivotal reason of the inhibitory action of genistein on leptin release.

PMID- 15970441
TI  - A simple precise technique for making the anterior cut in patellofemoral
      resurfacing.

PMID- 15970442
TI  - Dwindling competition with constant demand: can homeostatic adjustments explain
      age-associated changes in peripheral B cell selection?
AB  - The close relationship between specificity-based selection and homeostatic
      processes in maintaining peripheral B cell pools has become increasingly evident.
      Thus, age-associated changes observed within these pools may reflect homeostatic
      responses to proximal primary lesions. Marked shifts in the size and dynamics of
      most B lymphocyte subsets and their progenitors occur with age: perturbations in
      B lineage precursors result in reduced production of immature B lymphocytes in
      the bone marrow and transitional pools in the periphery, but these effects appear
      to be offset by compensatory homeostatic processes at the marrow-periphery
      interface. We propose a model whereby these "distal" homeostatic adjustments
      relax the stringency of specificity based selection, affording a potential
      explanation for the increased frequency of autoreactive specificities with age.

PMID- 15970443
TI  - Stromagenesis: the changing face of fibroblastic microenvironments during tumor
      progression.
AB  - During tumorigenesis, reciprocal changes in stromal fibroblasts and tumor cells
      induce changes to the neoplastic microenvironmental landscape. In stromagenesis,
      both the complex network of bi-directional stromal fibroblastic signaling
      pathways and the stromal extracellular matrix are modified. The presence of a
      'primed' stroma during the early, reversible stage of tumorigenesis is optimal
      for stromal-directed therapeutic intervention. Three-dimensional (3D) cell
      culture systems have been developed that mimic the in vivo microenvironment.
      These systems provide unique experimental tools to identify early alterations in
      stromagenesis that are supportive of tumor progression with the ultimate goal of
      blocking neoplastic permissiveness and restoring normal phenotypes.

PMID- 15970444
TI  - Molecular phylogeny of the subgenus Drosophila (Diptera, Drosophilidae) with an
      emphasis on Neotropical species and groups: a nuclear versus mitochondrial gene
      approach.
AB  - The genus Drosophila has played an essential role in many biological studies
      during the last 100 years but much controversy and many incompletely addressed
      issues still remain to be elucidated regarding the phylogeny of this genus.
      Because information on the Neotropical species contained in the subgenus
      Drosophila is particularly incomplete, with this taxonomic group being
      underrepresented in many studies, we designed a study to answer some evolutionary
      questions related to these species. We subjected at least 41 Drosophilidae taxa
      to a phylogenetic analysis using a 516-base pair (bp) fragment of the alpha
      methyldopa (Amd) nuclear gene and a 672 bp fragment of the mitochondrial
      cytochrome oxidase subunit II (COII) gene both individually and in combination.
      We found that the subgenus Drosophila is paraphyletic and subdivided into two
      main clusters: the first containing species traditionally placed in the virilis
      repleta radiation and the second assembling species of the immigrans
      Hirtodrosophila radiation. Inside the first of these clusters we could detect the
      monophyly of both the flavopilosa (the sister-clade of the annulimana group) and
      the mesophragmatica (closely related to the repleta group) species groups.
      Concerning the immigrans-Hirtodrosophila lineage, Zaprionus, Liodrosophila,
      Samoaia, and Hirtodrosophila were the early offshoots, followed by the immigrans,
      quinaria, testacea, and funebris species groups. The tripunctata radiation
      appears to be a derived clade, composed of a paraphyletic tripunctata group,
      intimately interposed with members of the cardini, guarani, and guaramunu species
      groups. Overall, the COII gene yielded a poor phylogenetic performance when
      compared to the Amd gene, the evolutionary hypothesis of which agreed with the
      total evidence tree. This phenomenon can be explained by the fast saturation of
      transitional substitutions in COII, due to strong biases in both base composition
      and substitution patterns, as also by its great among-site rate variation
      heterogeneity.

PMID- 15970445
TI  - Variation of cell and matrix morphologies in articular cartilage among locations
      in the adult human knee.
AB  - OBJECTIVE: Understanding of articular cartilage physiology, remodelling
      mechanisms, and evaluation of tissue engineering repair methods requires
      reference information regarding normal structural organization. Our goals were to
      examine the variation of cartilage cell and matrix morphology in different
      topographical areas of the adult human knee joint. METHODS: Osteochondral
      explants were acquired from seven distinct anatomical locations of the knee
      joints of deceased persons aged 20-40 years and prepared for analysis of cell,
      matrix and tissue morphology using confocal microscopy and unbiased stereological
      methods. Differences between locations were identified by statistical analysis.
      RESULTS: Medial femoral condyle cartilage had relatively high cell surface area
      per unit tissue volume in the superficial zone. In the transitional zone,
      meniscus-covered lateral tibia cartilage showed elevated chondrocyte densities
      compared to the rest of the knee while lateral femoral condyle cartilage
      exhibited particularly large chondrocytes. Statistical analyses indicated highly
      uniform morphology throughout the radial zone (lower 80% of cartilage thickness)
      in the knee, and strong similarities in cell and matrix morphologies among
      cartilage from the femoral condyles and also in the mediocentral tibial plateau.
      Throughout the adult human knee, the mean matrix volume per chondron was
      remarkably constant at approximately 224,000 microm(3), corresponding to
      approximately 4.6 x 10(6) chondrons per cm(3). CONCLUSIONS: The uniformity of
      matrix volume per chondron throughout the adult human knee suggests that cell
      scale biophysical and metabolic constraints may place limitations on cartilage
      thickness, mechanical properties, and remodelling mechanisms. Data may also aid
      the evaluation of cartilage tissue engineering treatments in a site-specific
      manner. Results indicate that joint locations which perform similar biomechanical
      functions have similar cell and matrix morphologies; findings may therefore also
      provide clues to understanding conditions under which focal lesions leading to
      osteoarthritis may occur.

PMID- 15970446
TI  - Evidence of a decrease in nitric oxide-storage molecules following acute hypoxia
      and/or hypobaria, by means of chemiluminescence analysis.
AB  - Nitrate, nitrite, and other nitroso compounds (NOxs) had been proposed as
      possible nitric oxide (NO) storage molecules. The present work examines, by means
      of chemiluminescence analysis, changes in NOx serum levels in rats 1 h before and
      24, 48, and 72 h after exposure to acute hypobaric hypoxia (HH; barometric
      pressure [P(B)] 225 mmHg, oxygen partial pressure [PO2] 48 mmHg), normobaric
      hypoxia (NH; P(B) 716 mmHg [Jaen city], PO2 48 mmHg), hypobaric normoxia (HN;
      P(B) 225 mmHg, PO2 150 mmHg), and normobaric normoxia (NN; P(B) 716 mmHg, PO2 150
      mmHg) the latter as a control group. Results show a decrease in NOx levels, which
      reached significance 24 h after exposure in HH animals, 4 h after exposure in the
      HN and NH groups, and persisted after 48 h of exposure in the HN group. NOx
      determinations were also performed in brain (cerebral cortex, hippocampus,
      decorticated brain [basal ganglia-brainstem] and cerebellum), liver, kidney,
      lung, and heart homogenates, 72 h after the experiment, to detect persistent
      effects when serum NOx levels had returned to basal values. Only in cerebellum
      (HN group) and hippocampus (HN and NH groups) were NOx levels significantly lower
      than in controls. We conclude that not only acute hypobaric hypoxia but also
      either hypobaria or hypoxia alone induce changes in NOx serum levels. Moreover,
      all three episodes involve a decrease in NOxs, greater and longer-lasting in
      hypoxia alone than in hypobaria and hypoxia together. The exhaustion of these NO
      storage molecules could be critical when, as during a hypoxic episode, the L
      arginine/NOS pathway is impaired.

PMID- 15970447
TI  - Rendering of quantum topological atoms and bonds.
AB  - In this article, we describe and apply an algorithm that visualizes atoms and
      bonds in molecules and van der Waals complexes, based on the topology of the
      electron density. The theory of quantum chemical topology defines both atoms and
      bonds via a single consistent procedure, and enables the association of an atomic
      shape with an atomic property (charge, dipole moment, volume, ...). Special
      attention is paid to the bridging of gaps arising in interatomic surfaces, in the
      presence of ring critical points or high ellipticity. This algorithm, in
      conjunction with the graphical user interface of the computer program MORPHY
      enables robust and efficient rendering of complicated interatomic surfaces, as
      found in larger systems.

PMID- 15970448
TI  - Effect of salmeterol on mucociliary and cough clearance in chronic bronchitis.
AB  - The effect of long acting beta(2)-adrenergic bronchodilators on impaired
      mucociliary clearance in chronic bronchitis is unknown. Using a radiolabeled
      aerosol (technetium-99m-labeled sulfur colloid) and gamma camera analysis, we
      measured the acute effect of salmeterol vs. placebo on mucociliary and cough
      clearance in mild-moderate chronic bronchitics (n = 14) over a 2h period. During
      the 1-1(1/2) h period of observation patients performed 60 controlled coughs on
      each study day. Average whole lung clearance through 1 and 2h after
      administration of salmeterol (42 microg) or placebo via metered dose inhaler
      (double-blinded, crossover design study) showed no significant difference between
      treatments. Similarly, for the specific period when cough was added to
      mucociliary clearance, there was no difference on whole lung clearance between
      treatments. However, when clearance from the peripheral region of the lung was
      assessed over the entire 2h period of observation, salmeterol provided a 30%
      enhancement of airway clearance compared to placebo, average peripheral 2h
      clearance (%) = 22 +/- 9 vs. 17 +/- 10 for salmeterol vs. placebo (P = 0.05 by
      paired analysis). Thus, in addition to its bronchodilating effects, salmeterol
      acutely enhances peripheral airway clearance of secretions in mild-moderate
      chronic bronchitis.

PMID- 15970449
TI  - p38 MAP kinase isoform activity and cell cycle regulators in the proliferative
      response of pulmonary and systemic artery fibroblasts to acute hypoxia.
AB  - Many cardiopulmonary diseases are associated with pulmonary hypertension which
      adds significant co-morbidity. Pulmonary hypertension is due partly to
      vasoconstriction but sustained by pulmonary vascular remodelling. If pathological
      endpoints are to be reversed in patients with pulmonary hypertension, the
      processes by which vascular remodelling occur need to be determined. Hypoxia
      provides a good model of pulmonary hypertension. We have previously shown that
      chronic hypoxia results in increased proliferation of pulmonary artery
      fibroblasts and stimulation of the mitogen-activated protein kinase (MAPK) family
      of signalling enzymes. Under the same conditions systemic artery fibroblasts were
      unaffected. This differential response of pulmonary fibroblasts to hypoxia
      represents a model to investigate the processes of pulmonary artery remodelling.
      The current study showed that acute hypoxia was capable of causing enhanced
      proliferation in pulmonary but not systemic artery fibroblasts and was linked to
      increased activation of p38 MAP kinase. Second, we have now shown that it is
      alpha and gamma isoforms of p38 MAP kinase, which are responsible. Third we have
      shown a link between stimulation of p38 MAP kinase and HIF-1 proportional,
      variant induction. An increased understanding of the effects of hypoxia on
      remodelling and proliferation represents a critical step in identifying targets
      for the treatment of pulmonary hypertension.

PMID- 15970450
TI  - Effects of tiotropium and other long acting bronchodilators in chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) accounts for a major workload in
      both primary and secondary care. It is characterised by progressive airflow
      obstruction which does not fully reverse to inhaled or oral pharmacotherapy. The
      diagnosis should be considered in any current or former smoker who has symptoms
      of breathlessness, wheeze, cough, sputum production and impaired exercise
      tolerance. From a pharmacological perspective, short-acting bronchodilators (anti
      cholinergics and beta(2)-agonists) play a vital role in immediate relief of
      symptoms. However, in patients with persistent symptoms and exacerbations, long
      acting bronchodilator therapy is advocated for regular use. Tiotropium is a newly
      introduced long-acting anti-cholinergic which facilitates once daily
      administration. This evidence based review article discusses the use of long
      acting bronchodilators in COPD with a particular emphasis on the putative
      benefits of tiotropium.

PMID- 15970451
TI  - A digestive beta-glucosidase from the silkworm, Bombyx mori: cDNA cloning,
      expression and enzymatic characterization.
AB  - A digestive beta-glucosidase cDNA was cloned from the silkworm, Bombyx mori. The
      B. mori beta-glucosidase cDNA contains an open reading frame of 1473 bp encoding
      491 amino acid residues. The B. mori beta-glucosidase possesses the amino acid
      residues involved in catalysis and substrate binding conserved in glycosyl
      hydrolase family 1. Southern blot analysis of genomic DNA suggested the B. mori
      beta-glucosidase to be a single gene. Northern blot analysis of B. mori beta
      glucosidase gene confirmed larval midgut-specific expression. The B. mori beta
      glucosidase mRNA expression in larval midgut was detectable only during feeding
      period, whereas its expression was downregulated during starvation. The B. mori
      beta-glucosidase cDNA was expressed as a 57-kDa polypeptide in baculovirus
      infected insect Sf9 cells, and the recombinant beta-glucosidase was active on
      cellobiose and lactose, but not active on salicin, indicating that the B. mori
      beta-glucosidase possesses the characteristics of the Class 2 enzyme. The enzyme
      activity of the purified recombinant beta-glucosidase expressed in baculovirus
      infected insect cells was approximately 665 U per microg of recombinant B. mori
      beta-glucosidase. The purified recombinant B. mori beta-glucosidase showed the
      highest activity at 35 degrees C and pH 6.0, and were stable at 50 degrees C at
      least for 10 min. Treatment of recombinant virus-infected Sf9 cells with
      tunicamycin, a specific inhibitor of N-glycosylation, revealed that the
      recombinant B. mori beta-glucosidase is N-glycosylated, but the carbohydrate
      moieties are not essential for enzyme activity.

PMID- 15970452
TI  - The feasibility of using cognitive behaviour therapy for depression associated
      with Parkinson's disease: a literature review.
AB  - Clinicians and researchers have called for more information on how to treat
      depression in Parkinson's disease. Cognitive Behaviour Therapy (CBT) has been
      identified as the treatment of choice for a range of psychological disorders and
      is increasingly applied to depression associated with chronic medical conditions.
      The present paper will review the relevant literature on CBT treatment
      effectiveness and the nature of depression in Parkinson's disease before
      suggesting how CBT might be adapted to assist this client group. The authors
      conclude that CBT is a promising option for depressed patients coping with
      Parkinson's disease, but further research is recommended.

PMID- 15970453
TI  - Hyperthyroidism exaggerating parkinsonian tremor: a clinical lesson.
AB  - We present the clinical description of a 70-year-old man with parkinsonian
      tremor, which was severely exaggerated by hyperthyroidism. Clinical diagnosis of
      hyperthyroidism was overshadowed by the parkinsonian symptoms. Anti-thyroid
      treatment had a beneficial effect on the exaggerated parkinsonian tremor. This
      case report highlights that thyroid dysfunction should be considered in the
      differential diagnosis of aggravated tremor in Parkinson's disease which seems
      refractory to increased dosages of anti-parkinsonian drugs.

PMID- 15970454
TI  - Neurochemical characterization of dopaminergic neurons in human striatum.
AB  - We examined the neurochemical phenotype of striatal neurons expressing tyrosine
      hydroxylase (TH) mRNA to determine if they form a distinct class of neurons
      within the human striatum. Double in situ hybridization (ISH) and
      immunohistochemical (IHC) procedures were used to know if TH mRNA-positive
      striatal neurons express molecular markers of mature neurons (MAP2 and NeuN),
      dopaminergic neurons (DAT and Nurr1) or immature neurons (TuJ1). All TH mRNA
      labeled neurons were found to express NeuN, DAT and Nurr1, whereas about 80% of
      them exhibited MAP2, confirming their neuronal and dopaminergic nature. Only
      about 30% of TH mRNA-labeled neurons expressed TuJ1, suggesting that this ectopic
      dopaminergic neuronal population is principally composed of mature neurons. The
      same double ISH/IHC approach was then used to know if these dopamine neurons
      display markers of well-established classes of striatal projection neurons (GAD65
      and calbindin) or local circuit neurons (GAD65, calretinin, somatostatin and
      parvalbumin). Virtually all TH-labeled neurons expressed GAD65 mRNA, about 30% of
      them exhibited calretinin, but none stained for the other striatal neuron
      markers. These results suggest that the majority of TH-positive neurons intrinsic
      to the human striatum belong to a distinct subpopulation of striatal interneurons
      characterized by their ability to produce dopamine and GABA.

PMID- 15970455
TI  - Increased genotoxic susceptibility of breast epithelial cells to ethylene oxide.
AB  - This study was carried out with the aim of elucidating the organ-specific effects
      of ethylene oxide in comparison with the sensitivity of cells from different
      tissues. An increased incidence of leukemia and lymphoma has been observed in
      workers exposed to ethylene oxide. However, contradictory findings exist
      regarding its ability to induce other tumor types, such as breast cancer. We
      characterized the genotoxicity of ethylene oxide by means of the alkaline version
      of comet assay in in vitro systems, in order to investigate the hypothesized role
      of this substance in the development of breast cancer. For this study, we used
      primary and secondary cultures of lymphoblasts (well-known target cells of the
      genotoxicity of ethylene oxide), breast epithelial cells (hypothesized target),
      peripheral blood lymphocytes (cells commonly used in biomonitoring), and of
      keratinocytes and cervical epithelial cells. DNA damage was measured and
      expressed as tail DNA, tail length, and tail moment. In the concentration range 0
      100 microM, ethylene oxide induced a dose-dependent increase of DNA damage in the
      investigated cell types without notable cytotoxicity. A statistically significant
      increase of DNA damage could be observed after treatment with 20 microM ethylene
      oxide in lymphoblasts (51% increase of tail moment over the background), breast
      epithelial cells (26% increase) and peripheral lymphocytes (71% increase). In
      keratinocytes (5% increase) and cervical epithelial cells (5% increase)
      significant DNA damage could not be detected at this dose, but at higher
      concentrations (50-100 microM), such an increase was observed. These results are
      indicative of an increased sensitivity of breast epithelial cells towards
      genotoxic insults of ethylene oxide. Our observations provide additional data to
      evaluate the hypothesis that exposure to ethylene oxide may play a role in breast
      cancer, and the findings may contribute to the development of screening tests for
      monitoring an early response to genotoxic insults in occupational settings.

PMID- 15970456
TI  - A Raman and infrared study of 1-furoyl-3-monosubstituted and 3,3-disubstituted
      thioureas.
AB  - Raman and IR spectra of two series of 1-furoylthiourea derivatives (19 compounds)
      were recorded and compared in order to identify the vibrations, which involve
      contributions from motions within the thioureido (NCSN) core. This procedure
      allowed an unequivocal identification of the nu(CS) vibration in these spectra.
      In 3-monosubstituted furoylthioureas (Series 2) the carbonyl group and the proton
      on N(3) are engaged in a strong hydrogen bond interaction. This leads to an "S"
      shaped conformation of the CO and CS groups where these donor sites reach a
      maximum separation. In this conformation, the nu(CO) vibration is not influenced
      by the substituent. In the absence of that hydrogen bridge, in 3,3-disubstituted
      thiourea derivatives (Series 1), the CO and CS groups adopt an "U"-shaped
      conformation. In this conformation, the nu(CO) vibration shows a pronounced
      substituent dependence. These thiourea derivatives have been tested as ionophores
      for heavy-metal ion selective electrodes and their behavior in that sense
      correlates with the observed Raman and IR absorptions. The best performance in
      that application corresponds to compounds of Series 2, which showed the highest
      frequency values of the nu(CS) vibration. This fact was related to an
      appropriated nucleophilic character of the sulphur atom. From these data, Raman
      and IR spectra of these thiourea derivatives could be used as a predictor on
      their expected behavior in analytical applications as ionophores.

PMID- 15970457
TI  - Study of the heavy atom-induced room temperature phosphorescence properties of
      melatonin and its analytical application.
AB  - Liquid phase room temperature phosphorescence (RTP) properties of melatonin were
      studied using heavy atom induced-room temperature phosphorescence (HAI-RTP)
      technique. 1.2 M potassium iodide was used as a heavy atom reagent together with
      0.002 M sodium sulphite as deoxygenating agent to produce the RTP signal. The
      maximum phosphorescence emission and excitation wavelengths of melatonin were 290
      and 457 nm, respectively. The effect of potassium iodide concentration on the RTP
      lifetime of melatonin was also investigated and based on the results, the rate
      constants for phosphorescence decay (k(p)) and radiationless deactivation through
      reaction with heavy atom (k(h)) were determined. Based on the obtained results, a
      simple and sensitive room temperature phosphorimetric method was developed for
      the determination of melatonin. The method allowed the determination of 10.0-200
      ng ml(-1) melatonin in aqueous solution with the limits of detection and
      quantification of 3.6 and 12 ng ml(-1), respectively. The proposed method was
      satisfactorily applied to the determination of melatonin in commercial
      pharmaceutical formulations.

PMID- 15970458
TI  - Optical spectra of some 6-styrylo-1H-pyrazolo[3,4-b]quinolines.
AB  - It was proposed a method of synthesis several 6-styrylo1-1H-pyrazolo[3,4
      b]quinolines as promising material for optoelectronics. Particularly, 6-styryl
      1,3-diphenyl-1H-pyrazolo[3,4-b]quinolines were prepared by Wadsworth-Emmons
      reaction. One of advantageous of these materials is stability of their optical
      spectra versus the possible cis- and trans-transformation. Theoretical and
      experimental studies of optical absorption and photoluminescence excitation
      spectra for styryloquinolines were done. They show that the AM1 semi-empirical
      method gives better results compared to other approaches. We have found that the
      solvents do not play a role in the behavior of the spectra. The backside
      substituted groups do not influence substantially the observed optical spectra.

PMID- 15970459
TI  - ThermoRaman spectroscopic study of kintoreite.
AB  - ThermoRaman spectroscopy has been used to study the molecular structure and
      thermal decomposition of kintoreite, a phosphated jarosite PbFe3(PO4)2(OH,H2O)6.
      Infrared spectroscopy shows the presence of significant amounts of water in the
      structure as well as hydroxyl units. In contrast, no water was observed for
      segnitite (the arsenojarosite) as determined by infrared spectroscopy. The Raman
      spectra at 77 K exhibit bands at 974.6, 1003.2 and 866.5 cm(-1). These bands are
      attributed to the symmetric stretching vibrations of (PO4)3-, (SO4)3- and (AsO4)3
      units. Raman spectroscopy confirms the presence of both arsenate and phosphate
      in the structure. Bands at 583.7 and 558.1 cm(-1) in the 77 K spectrum are
      assigned to the nu4 (PO4)3- bending modes. ThermoRaman spectroscopy of kintoreite
      identifies the temperature range of dehydration and dehydroxylation.

PMID- 15970460
TI  - Aggregation of acetic and propionic acid in argon matrices--a matrix isolation
      and computational study.
AB  - Monomeric acetic acid MA and propionic acid MP were isolated in argon matrices at
      10K by using a pulse deposition technique. The dimerization of the monomers was
      induced by warming the matrices from 10 to 40 K. Under these conditions the
      diffusion of small trapped molecules is rapid and the dimerization could be
      monitored directly by IR spectroscopy. Both carboxylic acids form the symmetrical
      dimers B with two strong C=O...HO hydrogen bridges as the thermodynamically most
      stable dimers. With acetic acid a less stable dimer AA could be obtained if high
      concentrations of acetic acid in argon were used during the deposition of the
      matrix. On annealing this dimer rearranges to the more stable BA. In contrast,
      propionic acid does not form a corresponding less stable dimer under any
      experimental condition. These observations are rationalized on the basis of DFT
      and ab initio calculations.

PMID- 15970461
TI  - SOM assembly of hydroxynaphthoquinone and its oxime: polymorphic X-ray structures
      and EPR studies.
AB  - Investigation on solvent-induced polymorphism in X-ray structures of 2-hydroxy
      1,4-naphthoquinone (Lawsone) 1, is carried out. In protic methanol, 1
      crystallizes in monoclinic space group P2(1)/c (1a) comprising of 2D hydrogen
      bonded network via cyclic dimers. In aprotic solvent such as acetone on the other
      hand, 1 exhibits orthorhombic space group Pna 2(1) (1b) and emerges with 1D
      catemeric chain. Solvent-induced topological isomerism of cyclic dimers and
      helical catemeric chains arising from (i) bifurcated intra- and inter molecular
      hydrogen bondings viz. O-H...O=C interactions between C(2) hydroxyl and C(1),
      C(4) carbonyls, (ii) C-H...O interactions viz. C(3)-H...O(1)C(1) have been
      discussed. A signal for radical in 1 at g = 2.0058 is signatured by EPR spectrum
      and it's oxime derivative viz. 2-hydroxy-4-naphthoquinone-1-oxime 2, in solid
      state shows biradical and monoradical formation with aggregation of dimer and
      monomer due to non-covalent hydrogen bonds. Zero field split parameters for 2 are
      estimated to be D = 215 G, Ex = 13 G, Ey = 47 G at 298 K. A half field signal at
      77 K indicates triplet ground state. Frozen glass EPR of 2 resolves as
      regioregular dimeric-monomeric species showing hyperfine interactions with 1
      oximino nitrogen in dimer A (14N) = 15.5 G].

PMID- 15970462
TI  - Experimental and quantum chemical study on the vibrational spectroscopy of N
      methylphenothiazines: part 1.
AB  - In this work the authors deal with the vibrational spectroscopy of three
      derivatives of phenothiazine: the 10-methyl-10H-phenothiazine, the 10 methyl-10H
      phenothiazine-3-carbaldehyde and the 10-methyl-10H-phenothiazine-3-yl-methanol.
      The authors investigated the vibrational spectroscopic behaviour of the
      phenothiazine skeleton and dealt with the aldehyde and the alcohol substituent
      effect on the vibrational spectroscopic and structural properties of these
      skeleton. The infrared and Raman spectra of the compounds have been recorded in
      condensed state. The Gaussian 98 program package was applied with the ab initio
      HF method since in this case beside the infrared also the Raman spectoroscopic
      properties appear in the output file. On the basis of the calculated force
      constants and geometric parameters, normal coordinate analysis was applied for
      the interpretation of the experimental vibrational spectra. Problems arose with
      the choice of the internal coordinates of the molecules. Full interpretations of
      the vibrational fundamentals of the compounds are presented. The relative mean
      deviations between the measured and calculated frequencies were below 1%.

PMID- 15970463
TI  - Branched-chain amino acid supplementation during the endoscopic injection
      sclerotherapy for esophageal varices may be useful for maintenance of nutritional
      status in patients with liver cirrhosis.

PMID- 15970464
TI  - Effect of oral branched chain amino acid-rich nutrient administered during
      endoscopic injection sclerotherapy of cirrhotic patients.
AB  - Endoscopic injection sclerotherapy (EIS) is conducted to treat esophageal varices
      associated with liver cirrhosis. Cirrhotic patients have protein energy
      malnutrition (PEM), and their malnutrition is aggravated during EIS due to
      dietary restrictions. The aim of this study was to evaluate the dietetic benefits
      of oral branched chain amino acid-rich nutrient (BCAA-rich nutrient) administered
      during EIS. Cirrhotic patients admitted for prophylactic EIS were divided into
      three groups: Group A given a general liquid nutrient in two divided doses, Group
      B given a BCAA-rich nutrient in two divided doses, and Group C given the BCAA
      rich nutrient in four divided doses. The nutritional state was evaluated based on
      physical examinations, biochemical parameters, and indirect calorimetry. A total
      of 29 patients were enrolled. Blood biochemical examinations showed a significant
      increase in the Fischer's ratio in Groups B and C. Group B showed significant
      decreases in resting energy expenditure/basal metabolic rate, while Group C
      showed a significant rise in non-protein respiratory quotient. The oxidation rate
      of carbohydrate significantly increased and that of fat significantly decreased
      in Group C. Administration of the BCAA-rich nutrient is considered to be useful
      in improving abnormalities of energy metabolism during EIS.

PMID- 15970465
TI  - Effects of tetrodotoxin and ion replacements on the short-circuit current induced
      by Escherichia coli enterotoxin STa across the colon of the gerbil (Gerbillu
      cheesmani) in different dietary states.
AB  - The effects of mucosally added Escherichia coli heat stable enterotoxin (STa, 30
      ng mL(-1)) on the basal short-circuit current (Isc in microA cm(-2)) across
      stripped and unstripped sheets of proximal, mid and distal colon were
      investigated. Samples were taken from fed, starved (4 days, water ad lib) and
      undernourished (50% of control food intake for 21 days) gerbils (Gerbillus
      cheesmani). The effect of neurotoxin tetrodotoxin (TTX 10 microM) and the effect
      of replacing chloride by gluconate or the effect of removing bicarbonate from
      bathing buffer on the maximum increase in Isc induced by E. coli heat stable
      enterotoxin STa were also investigated. The results showed that there is a
      segmental difference both in the basal and STa-induced Isc. Also, STa is more
      effective in the proximal than distal colon in the three feeding conditions.
      Undernourishment raised the STa-induced Isc in the three regions of the colon. In
      fed and starved gerbils part of STa-induced Isc in the proximal colon was
      chloride-dependent, while the other was bicarbonate-dependent; in the mid colon,
      the STa-induced Isc was bicarbonate-dependent only. In the three regions of the
      colon taken from undernourished gerbil, the STa-induced Isc was both chloride-and
      bicarbonate-dependent. The increase in STa-induced Isc as a results of
      undernourishment in proximal and mid colon was chloride-dependent, while in the
      distal colon, it was both chloride- and bicarbonate-dependent.

PMID- 15970466
TI  - Hypoxia-induced expression of HIF-1alpha and its target genes in umbilical venous
      endothelial cells of Tibetans and immigrant Han.
AB  - The better adaptation of native Tibetans to hypoxia is thought to be partly due
      to improved umbilical circulation, which results in reduced pre- and postnatal
      fatalities. We hypothesized that the difference in umbilical circulation between
      native Tibetans and other high-altitude inhabitants was due to differences in the
      expression of hypoxia-induced factor (HIF-1) and its target genes vascular
      endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). We
      tested this hypothesis by examining the effect of hypoxia on the expression of
      HIF-1alpha, VEGF, and iNOS in cultured umbilical venous endothelial cells (UVECs)
      from native Tibetans and immigrant Hans. UVECs were collected and cultured under
      hypoxic (0.5% oxygen) or normoxic conditions for 2, 4, 12 and 24 h. The mRNA
      levels of HIF-1alpha, VEGF, endothelial nitric oxide synthase (eNOS) and iNOS and
      the protein level of HIF-1alpha were determined with RT-PCR and Western blot
      analyses, respectively. In both immigrant Han and Tibetans, HIF-1alpha mRNA was
      constitutively expressed under normoxic condition, and remained constant after
      hypoxic exposure. In contrast, HIF-1alpha protein was undetectable under normoxic
      condition, but underwent dynamic changes in response to hypoxia. It was induced
      at 4 h, peaked at 12 h, and remained elevated at 24 h. Concurrent with the
      induction of HIF-1alpha protein, the mRNA levels of VEGF and iNOS were also up
      regulated whereas that of eNOS was down-regulated. The lack of a hypoxia-related
      difference in the expression of HIF-1alpha and its target genes suggests that HIF
      1alpha does not play a critical role in high altitude adaptation. Alternative
      mechanisms may be responsible for the better adaptation of native Tibetans.

PMID- 15970467
TI  - Analyzing the duration of recurrent events in clinical trials: a comparison of
      approaches using data from the UK700 trial of psychiatric case management.
AB  - In studies of chronic disease the outcome measure may be based upon the duration
      of recurring illness. Our example is the UK700 trial of psychiatric case
      management, where the total number of days spent in hospital over a 2-year follow
      up was the primary outcome. Investigations of treatment effect modifiers were
      undertaken using an analysis of that primary outcome, a comparison of length of
      hospitalizations, and also a multi-state modeling approach. The days in hospital
      outcome was relatively straightforward to analyze, and allowed the complete
      randomized treatment groups to be compared. In contrast, the comparison of length
      of hospitalizations included only hospitalized patients, with censored
      observations not being well accommodated. The multi-state model provided separate
      treatment effect estimates for admission and discharge, this being more
      informative about how any reduction in days spent in hospital is achieved.
      Estimation of the treatment effects through the use of proportional hazards
      regression allowed appropriate incorporation of censored observations. However,
      with the multi-state model approach treatment effect estimates are not based upon
      comparisons of complete randomized treatment groups, as individuals are removed
      from the risk set for admission whilst at risk for discharge, and vice versa. We
      conclude that total duration is an appropriate primary outcome for clinical
      trials, but that multi-state models deserve greater use as an informative
      secondary analysis.

PMID- 15970468
TI  - Mutations at Arginine 276 transform human uracil-DNA glycosylase into a single
      stranded DNA-specific uracil-DNA glycosylase.
AB  - To investigate the role of Arginine 276 in the conserved leucine-loop of human
      uracil-DNA glycosylase (UNG), the effects of six R276 amino acid substitutions
      (C, E, H, L, W, and Y) on nucleotide flipping and enzyme conformational change
      were determined using transient and steady state, fluorescence-based, kinetic
      analysis. Relative to UNG, the mutant proteins exhibited a 2.6- to 7.7-fold
      reduction in affinity for a doubled-stranded oligonucleotide containing a
      pseudouracil residue opposite 2-aminopurine, as judged by steady-state DNA
      binding-base flipping assays. An anisotropy binding assay was utilized to
      determine the K(d) of UNG and the R276 mutants for carboxyfluorescein-labeled
      uracil-containing single- and double-stranded oligonucleotides; the binding
      affinities varied 11-fold for single-stranded uracil-DNA, and 43-fold for double
      stranded uracil-DNA. Productive uracil-DNA binding was monitored by rapid
      quenching of UNG intrinsic protein fluorescence. Relative to UNG, the rate of
      intrinsic fluorescence quenching of five mutant proteins for binding double
      stranded uracil-DNA was reduced approximately 50%; the R276E mutant exhibited 1%
      of the rate of fluorescence quenching of UNG. When reacted with single-stranded
      uracil-DNA, the rate of UNG fluorescence quenching increased. Moreover, the rate
      of fluorescence quenching for all the mutant proteins, except R276E, was slightly
      faster than UNG. The k(cat) of the R276 mutants was comparable to UNG on single
      stranded DNA and differentially affected by NaCl; however, k(cat) on double
      stranded DNA substrate was reduced 4-12-fold and decreased sharply at NaCl
      concentrations as low as 20 mM. Taken together, these results indicate that the
      effects of mutations at Arg276 were largely limited to enzyme interactions with
      double-stranded uracil-containing DNA, and suggested that mutations at Arg276
      effectively transformed UNG into a single-stranded DNA-specific uracil-DNA
      glycosylase.

PMID- 15970469
TI  - Infection and inflammation in cystic fibrosis: a short review.
AB  - In most patients with cystic fibrosis (CF) life expectancy is limited due to a
      progressive loss of functional lung tissue. Already very early in life a
      persistent neutrophylic inflammation can be demonstrated in the airways. The
      cause of this inflammation, the role of CFTR and different CF specific bacteria
      like Pseudomonas aeruginosa are not well understood. This short review summarises
      the current understanding and hypothesis of the origin of this complicated
      process of inflammation and infection. Better understanding of this process may
      lead to the development of new treatment modalities of CF lung disease and
      consequent improvement of life expectancy.

PMID- 15970470
TI  - Cardiorespiratory effects of nicotine exposure during development.
AB  - Exposure to tobacco smoke is a major risk factor for the sudden infant death
      syndrome. Nicotine is thought to be the ingredient in tobacco smoke that is
      responsible for a multitude of cardiorespiratory effects during development, and
      pre- rather than postnatal exposure is considered to be most detrimental.
      Nicotine interacts with endogenous acetylcholine receptors in the brain and lung,
      and developmental exposure produces structural changes as well as alterations in
      neuroregulation. Abnormalities have been described in sympathicovagal balance,
      arousal threshold and latency, breathing pattern at rest and apnea frequency,
      ventilatory response to hyperoxia or hypoxia, heart rate regulation and ability
      to autoresuscitate during severe hypoxia. This review discusses studies performed
      on infants of smoking mothers and nicotine-exposed animals yielding varying and
      sometimes inconsistent results that may be due to differences in experimental
      design, species and the dose of exposure. Taken together however, developmental
      nicotine exposure appears to induce vulnerability during hypoxia and a potential
      inability to survive severe asphyxia.

PMID- 15970471
TI  - A cell-based system for hepatitis B virus replication: significance of clinically
      enhanced viral replication in relation to deletions in viral core promoter.
AB  - The core promoter of hepatitis B virus (HBV) is crucial in viral replication. Our
      previous investigation in clinical serum samples indicated that deletions in the
      viral core promoter (from nucleotide 1758 to 1777 and 1749 to 1768 respectively)
      may lead to increase in viral replication. We propose to characterize these
      deletion mutants in a cell-based system that supports HBV replication.
      Replicative HBV genome developed in our laboratory was used as template to
      generate deletions in viral core promoter corresponding to those found in
      clinical samples. These deletion constructs were used to transfect HepG2 cells,
      which then support the subsequent infection of cells from these deleted but
      replicative genomes. The effect of deletion on the viral replication was measured
      by comparing the amount of hepatitis B virus surface antigen (HBsAg) secreted in
      the culture medium with that from cells transfected with the wild type HBV
      genome. The amount of secreted HBsAg in cells transfected with deletion mutants
      was significantly lower than those transfected with the wild type genome. Our
      results provide a new system for molecular characterization of mechanism of HBV
      replication. Contrary to the increased replication observed in clinical samples,
      the reduced viral replication in genomes carrying deletions in the core promoter
      suggests a complex regulatory mechanism of viral replication which may involve
      other elements in the viral core promoter.

PMID- 15970472
TI  - A reagentless biosensor of nitric oxide based on direct electron transfer process
      of cytochrome c on multi-walled carbon nanotube.
AB  - Direct electron transfer between Cytochrome c (Cyt.c) and electrode can be
      achieved through immobilizing Cyt.c on the surface of multi-walled carbon
      nanotubes (MWNTs). Under the condition of cyclic potential scans, Cyt.c can be
      adsorbed on the surface of MWNTs that were modified on a glassy carbon (GC)
      electrode to form an approximate monolayer. The redox characteristic and
      bioactivity of Cyt.c could be remained after it was adsorbed on MWNTs' surface.
      This provides a way to construct a new biosenser based on the activity of Cyt.c.
      Further investigation displayed that Cyt.c adsorbed on MWNTs showed an enzyme
      like activity to catalyze the reduction of nitric oxide (NO). Due to catalyzing
      by Cyt.c, the reduction of NO in aqueous solution was achieved, which reductive
      potential appeared at -0.747V (vs. SCE). The peak currents were linearly
      proportional to concentration of NO in the range from 2 to 48 micromol/l with a
      limit of detection of 1.3 microM. The biosensor showed a good stability and
      excellent repeatability.

PMID- 15970473
TI  - Ouabain-induced cell signaling.
AB  - When endogenous ouabain was first isolated from human plasma in 1991, many
      expressed doubts that such a compound could be endogenous to humans because of
      its unusual structure, its unknown synthesis, and its unidentified site of
      origin. Furthermore, the relevance of human ouabain was questioned because of its
      apparently low (< or =nmol/L) circulating concentration. Since then, much
      progress has been made on the origin and synthesis of endogenous ouabain, but
      perhaps the most significant finding is that nanomolar concentrations of ouabain
      can induce numerous signal transduction events in both primary and immortalized
      cultures of cells. Here we analyze the effects of low ouabain-induced signals
      including cell proliferation, calcium mobilization, cell cytotoxicity, apoptosis,
      mitogen-activated protein kinase (MAPK) activation and other signaling pathways.
      Furthermore, we consider how these low dose ouabain-induced events might enable a
      putative role for human endogenous ouabain to be assigned.

PMID- 15970474
TI  - Regions conferring isoform-specific function in the catalytic subunit of the Na,K
      pump.
AB  - The Na,K-pump (i.e., Na,K-ATPase) is critical for maintaining the ionic gradients
      across the plasma membranes of animal cells. Its component subunits are expressed
      in multiple forms, but the physiological relevance of this subunit diversity
      remains unknown. The primary contributor to overall catalysis, the alpha subunit,
      exists in four isoforms. There are observed kinetic differences among these
      isoforms, but their subtlety makes them an unlikely basis for physiological
      significance. Instead, recent work suggests that the major functional distinction
      among the isoforms is their interaction with regulatory proteins. Moreover, the
      isoform-specific effects of modulatory agents such as protein kinase C seem to
      originate within two regions of structural divergence: the amino terminus and
      eleven residues near the center of the alpha subunit, the isoform-specific
      region.

PMID- 15970475
TI  - The human chondrosarcoma HCS-2/8 cell line is responsive to BMP-7, but not to IL
      1beta.
AB  - Cultures of primary chondrocytes as in vitro model systems for studying the
      cellular behavior of chondrocytes are notoriously difficult to cultivate and
      propagate. One way to circumvent these problems appears to be the use of
      immortalized/immortal chondrocytic cell lines. In the present study, we were
      interested whether the chondrosarcoma derived HCS-2/8 cells are suitable for
      studying major cellular reaction pattern in response to key anabolic (BMP-7) and
      catabolic (IL-1beta) factors. Therefore, we used cDNA array and real-time PCR
      technology in order to evaluate gene expression triggered by stimulation with IL
      1beta (0,1-100 ng/ml) and BMP-7 in confluent monolayer cultures. HCS-2/8 cells
      hardly responded to IL-1beta, but showed good responsiveness to BMP-7. We found
      12 genes up- and 17 significantly down-regulated by BMP-7 (out of 340
      investigated genes). Besides the expected activation of anabolic genes
      chondrocytic cells after BMP-stimulation try to neutralize activation of the BMP
      signalling cascade by expressing intra- and extracellular BMP-antagonists.
      Chondrosarcoma derived cell lines are a potential substitute for primary
      articular chondrocytes promising consistent expression of a differentiated
      chondrocyte phenotype with sufficient proliferative capacity. However, as shown
      by this study one needs to carefully select the cell line depending on the
      effects which one intends to study. In this respect, HCS-2/8 cells are a
      validated tool for studying BMP-effects on chondrocytes, but not e.g. effects of
      interleukin-1.

PMID- 15970476
TI  - Uremic cardiomyopathy: role of circulating digitalis like substances.
AB  - Patients with chronic renal failure develop a cardiomyopathy characterized by
      marked diastolic dysfunction and left ventricular hypertrophy. Interestingly,
      they also have substantial increases in the circulating concentrations of
      digitalis like substances. Digitalis like substances produce reactive oxygen
      species as part of the signal cascade induced by binding to the sodium pump and
      patients, and this signal cascade appears to induce hypertrophy of cardiac
      myocytes grown in culture. Also, patients with chronic renal failure develop an
      oxidant stress state without a known mechanism. From these data, we propose that
      it is these digitalis like substances which cause cardiomyopathy of renal failure
      as well as the systemic oxidant stress state.

PMID- 15970477
TI  - GRP78/BIP is involved in ouabain-induced endocytosis of the Na/K-ATPase in LLC
      PK1 cells.
AB  - We have demonstrated that ouabain causes dose- and time-dependent decreases both
      in 86Rb+ uptake and plasmalemmal Na/K-ATPase content of LLC-PK1 cells, which is
      related to ouabain-induced endocytosis of plasmalemmal Na/K-ATPase in LLC-PK1
      cells through a clathrin-dependent mechanism. GRP78/BiP is a resident protein of
      the endoplasmic reticulum (ER) and acts as a molecular chaperone. Recently,
      several studies have shown that GRP78/BiP is also expressed on the cell surface
      and forms heterogeneous, high molecular weight complexes with other proteins. To
      identify the proteins that are possibly involved in ouabain-induced endocytosis
      of the Na/K-ATPase in LLC-PK1 cells, we separated and identified endosomal
      proteins by 2D gel electrophoresis and MS/MS from both control and ouabain
      treated LLC-PK1 cells. GRP78/BiP was identified by MS/MS as one of the several up
      regulated proteins and confirmed by Western Blot. By using a cell surface protein
      biotinylation technique to isolate the cell surface membrane proteins, we found
      that GRP78/BiP is also expressed on the cell surface of LLC-PK1 cells, and
      surface-expressed GRP78/BiP is down regulated in a time-dependent manner in
      response to ouabain. By comparing the cellular redistributions, our data suggest
      that both the Na/K-ATPase alpha-1 subunit and GRP78/BiP follow the same
      redistribution pattern in response to ouabain.

PMID- 15970478
TI  - Ouabain-induced endocytosis and signal transduction of the Na/K-ATPase.
AB  - Na/K-ATPase can function as a signal transducer as well as an energy transducing
      ion pump. Cardiac glycosides (including ouabain and marinobufagin, MBG) are a new
      class of steroid hormones. Ouabain-activated signaling pathways lead to the
      induction of some early response proto-oncogenes, activation of transcription
      factors, and cardiac hypertrophy. Low concentration of ouabain also induced
      endocytosis of the Na/K-ATPase and compartmentalization of some signaling
      molecules (e.g. c-Src, EGFR, and p42/44 MAPKs) into clathrin-coated pits, early
      and late endosomes. Ouabain-induced endocytosis of the Na/K-ATPase depends on the
      activation of Src kinase, clathrin-coated pits formation, and caveolin-1 (the
      major component of caveolae). Moreover, low concentration ouabain significantly
      reduced transcellular Na+ transport. The data also show a stronge interplay of
      ouabain-induced endocytosis of the Na/K-ATPase and signaling transduction.

PMID- 15970479
TI  - HIV vaccine development.
AB  - For the past two decades, scientists have aggressively pursued the development of
      a vaccine against human immunodeficiency virus (HIV). The magnitude of this
      effort is unprecedented in the history of infectious diseases. However,
      difficulties in finding promising candidate vaccines have limited the number of
      clinical efficacy trials. The macaque model is well suited for the evaluation of
      potential vaccines, but comparison of results among studies is often complicated
      by the use of different macaque species and/or challenge viruses. This review
      discusses current results obtained in the macaque model and human vaccine trials.

PMID- 15970480
TI  - Uncoupling protein-2 and non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) has become the most common form of
      hepatic disorders in the developed world. NAFLD is part of the metabolic syndrome
      with insulin resistance as a primary underlying derangement. The natural history
      of NAFLD may extend from simple steatosis over steatohepatitis into cirrhosis and
      hepatocellular carcinoma. Among numerous factors shaping these transitions,
      uncoupling protein-2 (UCP2) may theoretically contribute to every stage of this
      disease. UCP2 is a recently identified fatty acid-responsive mitochondrial inner
      membrane carrier protein showing wide tissue distribution with a substantially
      increased presence in fatty liver. The biological functions of UCP2 are not fully
      elucidated and the greater part of our current knowledge has been obtained from
      animal experiments. These data suggest a role for UCP2 in lipid metabolism,
      mitochondrial bioenergetics, oxidative stress, apoptosis, and even
      carcinogenesis. Available evidence is reviewed and new concepts are considered to
      appraise the potential role of UCP2 in the pathogenesis of NAFLD.

PMID- 15970481
TI  - Molecular properties of mammalian proteins that interact with cGMP: protein
      kinases, cation channels, phosphodiesterases, and multi-drug anion transporters.
AB  - Cyclic GMP is a critical second messenger signaling molecule in many mammalian
      cell types. It is synthesized by a family of guanylyl cyclases that is activated
      in response to stimuli from hormones such as natriuretic peptides, members of the
      guanylin family, and chemical stimuli including nitric oxide and carbon monoxide.
      The resulting elevation of cGMP modulates myriad physiological processes. Three
      major groups of cellular proteins bind cGMP specifically at allosteric sites;
      interaction of cGMP with these sites modulates the activities and functions of
      other domains within these protein groups to bring about physiological effects.
      These proteins include the cyclic nucleotide (cN)-dependent protein kinases, cN
      gated cation channels, and cGMP-binding phosphodiesterases (PDE). Cyclic GMP also
      interacts with the catalytic sites of many cN PDEs and with some members of the
      multi-drug anion transporter family (MRPs) which can extrude nucleotides from
      cells. The allosteric cN-binding sites in the kinases and the cN-gated channels
      are evolutionarily and biochemically related, whereas the allosteric cGMP-binding
      sites in PDEs (also known as GAF domains), the catalytic sites of PDEs , and the
      ligand-binding sites in the MRPs are evolutionarily and biochemically distinct
      from each other and from those in the kinase and channel families. The sites that
      interact with cGMP within each of these groups of proteins have unique properties
      that provide for cGMP binding. Within a given cell, cGMP can potentially interact
      with members of all these groups of proteins if they are present. The relative
      abundance and affinities of these various cGMP-binding sites in conjunction with
      their subcellular compartmentation, proximity to cyclases and PDEs, and post
      translational modification contribute importantly in determining the impact of
      these respective proteins to cGMP signaling within a particular cell.

PMID- 15970482
TI  - Progesterone receptors: various forms and functions in reproductive tissues.
AB  - The unequivocal role of progesterone in a variety of events like ovulation,
      mammary gland development, establishment and maintenance of pregnancy etc are
      well established. Also the data are accumulating on its role in male reproductive
      events. In vertebrates and humans, the biological activity of progesterone is
      mediated by two progesterone receptor proteins PR-A and PR-B, that arise from the
      same gene and are the members of nuclear receptor superfamily of transcriptional
      factors. Several studies have demonstrated that the blockage of progesterone
      receptor using antiprogestins impairs folliculogenesis, ovulation, implantation
      and pregnancy. Progesterone receptor (PR), have also been detected in human
      spermatozoa. However, unlike the conventional PR, sperm PR was localized on the
      membrane and showed distinct characteristics in terms of its size. There are data
      to demonstrate the inhibition of progesterone driven functions such as
      hyperactive motility, acrosome reaction on neutralization of sperm membrane PR
      with specific antibodies against PR. Further significant decrease in the % of PR
      positive spermatozoa was observed in infertile cases as compared to the fertile
      men. This indicated that PR can serve as the marker to define the fertilizing
      potential of the spermatozoa. Recently we have also shown that the PR is
      expressed in human testis. This reinforced that this PR protein is an inherent
      testicular protein and not a secretion of accessory reproductive organs. This
      review compiles the major observations on the forms of the progesterone receptor
      in various reproductive tissues.

PMID- 15970483
TI  - The neuroprotective and angiogenesis inhibitory serpin, PEDF: new insights into
      phylogeny, function, and signaling.
AB  - Pigment Epithelial-Derived Factor (PEDF) is a non inhibitory serpin with
      neuroprotective and antiangiogenic actions. It is a potent and broadly acting
      neurotrophic factor that protects neurons from many regions of the CNS against a
      wide range of neurodegenerative insults including glutamate toxicity and
      oxidative stress. PEDF also functions as a natural inhibitor of angiogenesis,
      targeting the growth of only new vessels. The 50 kD protein is encoded by a
      single gene that shows strong conservation across phyla from fish to mammals. Two
      specific domains on the PEDF protein interact with extracellular matrix
      components and may mediate some of the biological actions of this protein. The
      transducers through which PEDF signals neurons and endothelial cells are defined
      and involves major pathways including Akt/NFkB , MAPK, and the caspases. PEDF is
      widely expressed in the nervous system and in most tissues of the body. A
      significant amount of the protein is found in the cerebral spinal fluid and
      circulating plasma as well. Therapeutic administration of the soluble protein or
      viral-mediated transfer of the gene in experimental in vivo models suggests that
      PEDF is an excellent pharmacological tool for slowing the progression of a range
      of neurodegenerative diseases and those pathologies associated with abnormal
      vessel growth in the eye and metastatic cancers of various tissues.

PMID- 15970484
TI  - Molecular properties and biological functions of cGMP-dependent protein kinase
      II.
AB  - Type II cGMP-dependent protein kinase (cGK II) is the protein product of one of
      two genes coding for cGKs in mammalian genomes. cGK II has a domain structure
      similar to cGK I (alpha or beta) consisting of an N-terminal regulatory domain,
      which contains a dimerization and an autoinhibitory region, two cGMP-binding
      domains and a C-terminal catalytic domain. However, the position of the high and
      low affinity cGMP-binding-domains in cGK II are reversed in comparison to cGK I.
      Moreover, the isoenzymes exhibit a different affinity towards various membrane
      permeable cGMP-analogs, allowing differentiation between the cGKs. Type II cGK is
      bound to the membrane by a myristoyl moiety. It has a distinct function and an
      expression pattern distinct from that of cGKI, being expressed predominantly in
      intestine, brain, and kidney. It is involved in regulating electrolyte and water
      secretion by epithelial tissues in response to the luminocrinic hormones guanylin
      and uroguanylin and in the secretory diarrhea provoked by heat-stable
      enterotoxins. Type II cGK also plays a role in the regulation of endochondral
      ossification by C-type natriuretic peptide, in renin secretion by the kidney,
      aldosterone secretion by the adrenal, and in the adjustment of the biological
      clock.

PMID- 15970485
TI  - Na/K-ATPase, endogenous digitalis like compounds and cancer development -- a
      hypothesis.
AB  - The primary transport system of sodium and potassium across the plasma cell
      membrane, the Na/K-ATPase, is a vital enzyme involved in numerous cellular
      events. This enzyme is the receptor for plant and amphibian steroids such as
      ouabain, digoxin and bufalin. In the past decade several endogenous steroids,
      identical or similar to the plant and amphibian steroids, termed here
      collectively digitalis-like compounds (DLC), have been identified in human
      tissues. This paper raises the hypothesis that alterations in the metabolism of
      endogenous DLC and in their interactions with the Na/K-ATPase may be associated
      with the development of malignancies. This hypothesis is based on the review of
      the literature pointing to: 1. An abnormal activity of the Na/K-ATPase and its
      sensitivity to DLC in malignant cells; 2. Abnormal plasma DLC concentrations in
      cancer patients; 3. Abnormal synthesis and release of DLC in immune compromised
      mice; and 4. Beneficial effects of DLC in the treatment of cancer.

PMID- 15970486
TI  - Evolution of clams (cholinesterase-like adhesion molecules): structure and
      function during development.
AB  - The protein family known as CLAMS (cholinesterase-like adhesion molecules) forms
      a novel class of heterophilic cell adhesion proteins. Family members are found
      through a wide range of metazoans and play a role during the development of
      multiple tissues. The majority of members of this family are transmembrane
      proteins with an extracellular domain that is conserved with cholinesterases
      including acetylcholinesterase. Yet all family members lack one or more of the
      residues that make up the catalytic triad necessary for enzymatic function.
      Therefore the conserved cholinesterase-like domain is not necessary for enzymatic
      function but does appear to play a role in heterophilic binding. CLAMS are
      expressed in a wide array of tissues and most family members appear to play a
      role in cell adhesion and junction formation. The development of junctions
      including septate junctions and synaptic junctions require CLAM family members
      such as Gliotactin and Neuroligins respectively. Modeling of the cholinesterase
      like domain reveals that evolutionary changes to the binding pocket of the
      cholinesterase domain may produce a range of different ligand binding partners
      for CLAM family members. In this vein, previous chimera experiments and recent
      work has identified mutations in CLAM family members that affect the structure of
      the cholinesterase-like domain. These mutant forms affect protein function during
      the development of specialized junctions and confirm the role of the
      cholinesterase domain in mediating heterophilic binding.

PMID- 15970487
TI  - Fever and hypothermia in systemic inflammation: recent discoveries and revisions.
AB  - Systemic inflammation is accompanied by changes in body temperature, either fever
      or hypothermia. Over the past decade, the rat and mouse have become the
      predominant animal models, and new species-specific tools (recombinant antibodies
      and other proteins) and genetic manipulations have been applied to study fever
      and hypothermia. Remarkable progress has been achieved. It has been established
      that the same inflammatory agent can induce either fever or hypothermia,
      depending on several factors. It has also been established that experimental
      fevers are generally polyphasic, and that different mechanisms underlie different
      febrile phases. Signaling mechanisms of the most common pyrogen used, bacterial
      lipopolysaccharide (LPS), have been found to involve the Toll-like receptor 4.
      The roles of cytokines (such as interleukins-1beta and 6 and tumor necrosis
      factor-alpha) have been further detailed, and new early mediators (e.g.,
      complement factor 5a and platelet-activating factor) have been proposed. Our
      understanding of how peripheral inflammatory messengers cross the blood-brain
      barrier (BBB) has changed. The view that the organum vasculosum of the lamina
      terminalis is the major port of entry for pyrogenic cytokines has lost its
      dominant position. The vagal theory has emerged and then fallen. Consensus has
      been reached that the BBB is not a divider preventing signal transduction, but
      rather the transducer itself. In the endothelial and perivascular cells of the
      BBB, upstream signaling molecules (e.g., pro-inflammatory cytokines) are switched
      to a downstream mediator, prostaglandin (PG) E2. An indispensable role of PGE2 in
      the febrile response to LPS has been demonstrated in studies with targeted
      disruption of genes encoding either PGE2-synthesizing enzymes or PGE2 receptors.
      The PGE2-synthesizing enzymes include numerous phospholipases (PL) A2,
      cyclooxygenases (COX)-1 and 2, and several newly discovered terminal PGE
      synthases (PGES). It has been realized that the "physiological," low-scale
      production of PGE2 and the accelerated synthesis of PGE2 in inflammation are
      catalyzed by different sets of these enzymes. The "inflammatory" set includes
      several isoforms of PLA2 and inducible isoforms of COX (COX-2) and microsomal (m)
      PGES (mPGES-1). The PGE2 receptors are multiple; one of them, EP3 is likely to be
      a primary "fever receptor." The effector pathways of fever start from EP3-bearing
      preoptic neurons. These neurons have been found to project to the raphe pallidus,
      where premotor sympathetic neurons driving thermogenesis in the brown fat and
      skin vaso-constriction are located. The rapid progress in our understanding of
      how thermoeffectors are controlled has revealed the inadequacy of set point-based
      definitions of thermoregulatory responses. New definitions (offered in this
      review) are based on the idea of balance of active and passive processes and use
      the term balance point. Inflammatory signaling and thermoeffector pathways
      involved in fever and hypothermia are modulated by neuropeptides and peptide
      hormones. Roles for several "new" peptides (e.g., leptin and orexins) have been
      proposed. Roles for several "old" peptides (e.g., arginine vasopressin,
      angiotensin II, and cholecystokinin) have been detailed or revised. New
      pharmacological tools to treat fevers (i.e., selective inhibitors of COX-2) have
      been rapidly introduced into clinical practice, but have not become magic bullets
      and appeared to have severe side effects. Several new targets for antipyretic
      therapy, including mPGES-1, have been identified.

PMID- 15970488
TI  - Sympathetic excitotoxicity in sepsis: pro-inflammatory priming of macrophages by
      norepinephrine.
AB  - In the history of medicine, the interaction between mind and body has been
      repeatedly proposed. However, the influence of the nervous system on the immune
      regulation has, until now, drawn little attention. In this regard, the adrenergic
      system has been explored, and mainly catecholamine-mediated anti-inflammatory
      effects have been described. These inhibitory effects of epinephrine and
      norepinephrine were found to be mediated by beta2-adrenoceptors expressed on
      mononuclear cells. Recently, the role of the parasympathetic nervous system in
      the local anti-inflammatory reflex has been investigated. Stimulation of the
      vagus nerve decreases the pro-inflammatory response of macrophages via alpha7
      cholinergic receptors. Thus, both the sympathetic and parasympathetic nervous
      systems are thought to work hand in hand in their anti-inflammatory responses.
      Here we discuss the deteriorating effects of the release of norepinephrine in
      sepsis. We have discovered that organ dysfunction in severe sepsis is mediated at
      least in part by an increase in pro-inflammatory cytokine release from Kupffer
      cells, which is caused by a priming via gut-derived norepinephrine. The
      sympathetic nervous system and gut-derived norepinephrine mediate the pro
      inflammatory effects by activating alpha2A-adrenoceptor on Kupffer cells. In this
      review, we will focus on the differential function of the noradrenergic system on
      local and systemic inflammatory responses and the possibilities of the modulation
      of sympathetic outflow by centrally active inhibitors such as the novel peptide
      ghrelin or NMDA-receptor blockers. Furthermore, we will introduce the new concept
      of "sympathetic excitotoxicity in sepsis" characterized by the neurogenic priming
      of the systemic pro-inflammatory response.

PMID- 15970490
TI  - Chronic drug exposures during development in nonhuman primates: models of brain
      dysfunction in humans.
AB  - This review of our work presents three specific examples of how nonhuman primates
      (rhesus monkeys, Macaca mulatta) have been used to study the effects of chronic
      drug exposures on brain function during different stages of development. In all
      cases, exposure levels similar to those experienced by humans were employed and
      the focus was on long-term--not acute--effects. In the case of the marijuana
      studies, exposures occurred during the adolescent period; for the cocaine
      studies, exposures occurred in binge-like fashion entirely before birth (in
      utero); and for the remacemide studies, exposures occurred daily in juveniles,
      prior to adolescence. An automated battery of behavioral tasks, the National
      Center for Toxicological Research Operant Test Battery (NCTR OTB), designed to
      assess aspects of motivation, visual discrimination, time perception, short-term
      memory, and learning, was used to monitor treatment effects. Chronic marijuana
      smoke exposure resulted in an 'amotivational' syndrome--even in weekend-only
      smokers--that resolved within three months of exposure cessation. In utero
      cocaine exposure was shown to cause behavioral rigidity or lack of plasticity as
      evidenced by the difficulty of subjects to adjust to rules changes for some OTB
      tasks. These effects were seen in adult subjects suggesting that the effects of
      gestational cocaine exposure are long-term or permanent. In addition, animals
      exposed to cocaine in utero were less sensitive to the behaviorally-disrupting
      effects of cocaine as adults. Remacemide caused profound and long-lasting,
      perhaps permanent, changes in learning task performance and because performance
      of this same task by children is significantly correlated with traditional
      measures of intelligence (IQ), these data suggest that such treatment may provide
      a valuable model of chemically-induced mental retardation.

PMID- 15970489
TI  - Zinc and zinc transporters in normal prostate and the pathogenesis of prostate
      cancer.
AB  - Zinc is an essential metal for all cells. It plays a role in a wide variety of
      physiological and biochemical processes. In the prostate epithelial cell the
      accumulation of high cellular zinc is a specialized function that is necessary
      for these cells to carry out the major physiological functions of production and
      secretion of citrate. The production of citrate and its secretion into prostatic
      fluid is a differentiated function of the prostate epithelial cells that is
      apparently important for reproduction. The loss of citrate and zinc accumulation
      is the most consistent and persistent characteristic of prostate malignancy. This
      characteristic of prostate cancer indicates that the lost ability of the
      malignant cells to accumulate zinc and citrate is an important factor in the
      development and progression of malignancy. The lost ability of the epithelial
      cells to accumulate zinc and thus to also accumulate citrate is the result of
      decreased expression of specific zinc uptake transporters. The purpose of this
      presentation is to review the current understanding of zinc and zinc homeostasis
      in the prostate and the role of zinc and zinc transporters in the normal function
      of the prostate and the pathogenesis of prostate cancer.

PMID- 15970491
TI  - Cardenolide and bufadienolide ligands of the sodium pump. How they work together
      in NaCl sensitive hypertension.
AB  - For the past 50 years biomedical scientists have been in quest of an unidentified
      factor (hormone) that elevates blood pressure and regulates renal sodium
      transport, i.e., natriuretic hormone. Recent discoveries have led to the
      identification of such factors which are present in humans, rodents and
      amphibians, and which, in a complex manner, interact with each other and with the
      other regulatory systems. In experimental NaCl sensitive hypertension brain
      endogenous ouabain, via activation of renin-angiotensin system and of sympathetic
      nervous system, stimulates adrenocortical production of marinobufagenin, a
      natriuretic and a vasoconstrictor. The combined effects of these endogenous
      factors may account for the classical properties attributed by Dahl, deWardener
      and others to the hypothetical "natriuretic hormone".

PMID- 15970492
TI  - Endogenous digitalis-like ligands and Na/K-ATPase inhibition in experimental
      diabetes mellitus.
AB  - Dysregulation of the Na/K-ATPase (NKA) in the kidney, cardiovascular system, and
      peripheral nervous system is believed to contribute to pathogenesis of diabetes
      mellitus (DM) and its complications. Recently we demonstrated that, in addition
      to endogenous ouabain (EO), mammalian tissues contain another NKA inhibitor, a
      bufadienolide marinobufagenin (MBG). In vitro MBG, a natriuretic and a
      vasoconstrictor, acts as a selective inhibitor of alpha-1 NKA, the main isoform
      of the sodium pump in renal tubules and vascular smooth muscle. To determine
      whether digitalis-like NKA inhibitors are linked to NKA dysregulation in DM, we
      studied changes in renal excretion and plasma levels of MBG and EO and the
      activity of erythrocyte NKA in male Wistar rats with type 1 DM and type 2 DM.
      Rats with type 1 DM were studied four weeks following a single intraperitoneal
      injection of 65 mg/kg streptozotocin (STZ)(n = 12), and rats with type 2 DM were
      studied 10 weeks after intraperitoneal injection of STZ during the neonatal
      period (n = 12). Renal excretion and plasma levels of EO did not change in rats
      with both types of DM as compared to that in the control groups. Renal excretion
      (57.5 +/- 9.4 pmol/kg/ 3 hours vs. 12.6 +/- 2.1 pmol/kg/ 3 hours; P less than
      0.01) and plasma levels (2.23 +/- 0.82 nmol/L vs. 0.29 +/- 0.07 nmol/L; P less
      than 0.01) of MBG increased, and NKA activity in erythrocytes was inhibited by
      50% in rats with type 1 DM as compared to controls. In rats with type 2 DM,
      plasma levels (1.48 +/- 0.09 nmol/L vs. 0.46 +/- 0.02 nmol/L; P less than 0.01)
      and renal excretion (21.3 +/- 3.2 pmol/kg/ 3 hours vs. 13.1 +/- 2.1 pmol/kg/ 3
      hours) of MBG also became elevated, but less than in the animals with type 1 DM.
      Accordingly, activity of NKA in erythrocytes from rats with type 2 DM was
      inhibited by 35%. In vitro treatment of erythrocytes from rats with type 1 and
      type 2 DM with anti-MBG antibody reversed the DM induced inhibition of the NKA.
      These results suggest that digitalis-like factors are involved in the
      pathogenesis of DM and that MBG, rather than EO, is responsible for DM-induced
      NKA inhibition.

PMID- 15970493
TI  - Applications of two-photon microscopy in the neurosciences.
AB  - Thanks to deep tissue penetration of infrared light (IR), two-photon laser
      scanning microscopy (2PLSM) has become an important tool in modern neuroscience.
      Examples range from the high-resolution visualization of dendritic spines in
      single neurons to the monitoring of intracellular Ca++ transients in small neural
      networks. In the present review we give an overview of the current achievements
      and discuss emerging applications of the technique.

PMID- 15970494
TI  - Enhanced green fluorescence protein tracks trichosanthin in human choriocarcinoma
      cells as a feasible and stable reporter.
AB  - Trichosanthin (TCS) is a ribosome-inactivating protein (RIP) which can inhibit
      the growth of human choriocarcinoma (JAR) cells. There are no clear mechanisms to
      discover the interaction pathway and cytotoxicity of TCS in JAR cells. In this
      paper, we showed the distribution and transport of endogenously expressed TCS in
      JAR cells. Enhanced Green Fluorescence Protein (EGFP), fused with TCS, was
      applied as a reporter to track the behavior of TCS in JAR cells. Firstly, we
      investigated the expression stability of EGFP and physiological effects on JAR
      cells. A stable cell line expressing EGFP was created, which could reproduce and
      express EGFP even if transplanted into nude mice. Based on the proved stability
      and feasibility of EGFP in cultured cells and in vivo, the fusion gene of EGFP
      and TCS was constructed and transfected into JAR cells by liposome. The
      fluorescence microscopy showed that TCS-EGFP fusion gene was expressed in JAR
      cells in 24 to 48 hours and the fluorescence spread in cytoplasm mainly and in
      nucleus partially, which could trace the distribution and transport of TCS-EGFP
      in JAR cells. Most of fluorescent cells died after 48 hours for the cytotoxicity
      of expressed TCS-EGFP. These results first reported a stable expression and
      tracing method by EGFP in JAR cells, and provided theoretical basis to apply TCS
      in cancer therapy.

PMID- 15970495
TI  - Cancer vaccines: the challenge of developing an ideal tumor killing system.
AB  - Despite the evidence that the immune system plays a significant role in
      controlling tumor growth in natural conditions and in response to therapeutic
      vaccination, cancer cells can survive their attack as the disease progresses and
      no vaccination regimen should be currently proposed to patients outside
      experimental clinical trials. Clinical results show that the immune system can be
      actively polarized against malignant cells by means of a variety of vaccination
      strategies, and that in some cases this is associated with tumor regression. This
      implies that under some unique circumstances, the naturally "dormant" immune
      effectors can actually be put at work and used as endogenous weapons against
      malignant cells. Consequently, the main challenge of tumor immunologists appears
      to lie on the ability of reproducing those conditions in a larger set of
      patients. The complexity of the immune network and the still enigmatic host-tumor
      interactions make these tasks at the same time challenging and fascinating.
      Recent tumor immunology findings are giving new impetus to the development of
      more effective vaccination strategies and might revolutionize the way of
      designing the next generation of cancer vaccines. In the near future, the
      implementation of these insights in the clinical setting and the
      completion/conduction of comparative randomized phase III trials will allow
      oncologists to define the actual role of cancer vaccines in the fight against
      malignancy.

PMID- 15970496
TI  - Non-alcoholic fatty liver disease (NAFLD) in children.
AB  - Childhood NAFLD has become an important childhood liver disease, and it is
      probably highly prevalent. The full of spectrum of NAFLD has been identified in
      children. It is not currently known whether or not simple hepatic steatosis in
      children is benign or whether it evolves to NASH over time. In contrast,
      childhood NASH certainly can have serious consequences. Cirrhosis is apparently
      rare in children with NAFLD, but it definitely occurs. Childhood NAFLD may occur
      in very young children, and there is no female predominance in the pediatric age
      bracket. Children present with vague abdominal pain, if they have any symptoms at
      all, but frequently hepatic steatosis is found incidentally on abdominal imaging.
      Laboratory studies show that serum aminotransferase abnormalities are rather
      moderate, with serum alanine aminotransferase (ALT) more elevated than serum
      aspartate aminotransferase (AST). Hypertriglyceridemia is the typical blood lipid
      abnormality, although hypercholesterolemia may occur. NASH may be more severe in
      children from certain ethnic groups, including Hispanics and Asians, or in
      association with certain metabolic disorders characterized by abnormalities in
      insulin receptor structure or signaling, such as lipodystrophy syndromes. Weight
      loss through dietary redesign and a regimen of regular exercise remains the
      mainstay for treatment for childhood NAFLD. A dietary strategy to minimize
      postprandial hyperinsulinemia and overall fat intake, such as a low glycemic
      index diet, may be the best dietary strategy. The real efficacy of drug
      treatments in children requires further investigation. The overriding message is
      that childhood obesity poses important health problems, including but not limited
      to potentially severe chronic liver disease. Early diagnosis of children who are
      only overweight is a worthy goal so that strategies to limit obesity can be
      instituted as early as possible. Identification of genetic risks is important,
      but management will invariably require changes in environmental factors. In
      addition to individual treatment, a multifaceted, societal initiative is required
      for solving the childhood obesity epidemic.

PMID- 15970497
TI  - Expression of aldehyde dehydrogenase 2 in the normal esophageal epithelium and
      alcohol consumption in patients with esophageal cancer.
AB  - Alcohol consumption is a risk factor for esophageal cancer. Acetaldehyde, a
      highly toxic intermediate produced from ethanol, is converted to acetic acid
      mainly by aldehyde dehydrogenase 2 (ALDH2) in the metabolic pathway of ethanol.
      Fifty percent of Japanese have inactive ALDH2 due to genetic polymorphism, which
      is considered to be a risk factor associated with esophageal cancer. In our
      previous study, we have demonstrated that ALDH2 is expressed in the esophagus
      with a considerable variation among individuals. In this study, we further
      investigated the expression of ALDH2 in esophagus and its relationship with risk
      factors of esophageal cancer. Tissue specimens resected from 51 patients with
      esophageal cancer were analyzed by immunohistochemistry using ALDH2-antibody. The
      immuno-staining of ALDH2 in the esophageal epithelium was compared with both the
      drinking habit and the occurrence of flushing that is closely associated with the
      ALDH2 deficiency. ALDH2 was not detectable in 8 (16%) among 51 specimens. All of
      the 8 patients were non- or light-drinkers but not heavy-drinkers. Among 18
      patients showing the high level ALDH2 expression in the esophagus, 15 patients
      (83%) were heavy-drinkers. Although the relationship between the ALDH2 deficiency
      and drinking habit is not clear, the patients with ALDH2 deficiency tend to be
      non- or light drinkers while heavy-drinkers tend to have the active form of
      ALDH2. These results suggest that both inactive and active forms of ALDH2 are
      induced in the esophagus by heavy drinking and also support a hypothesis that
      ALDH2 deficiency might be a high-risk factor of esophageal cancer for the
      individuals having a heavy-drinking habit. To our knowledge, this is the first
      study demonstrating the induction of ALDH2 in the esophagus by ethanol
      consumption.

PMID- 15970498
TI  - Endogenous digitalis-like factors. An historical overview.
AB  - The sodium pump is a ubiquitous cell surface enzyme, a Na/K-ATPase, that
      maintains ion gradients between cells and the extracellular fluid. The
      extracellular domain of this enzyme contains a highly conserved receptor for a
      plant-derived family of compounds, the digitalis glycosides, used in the
      treatment of congestive heart failure, and certain cardiac arrhythmias. The
      concept that an endogenous modulator of this enzyme, analogous to the cardiac
      glycosides, emerged from work on two separate areas: the regulation of
      extracellular fluid (ECF) volume by a natriuretic hormone (NH), and the
      regulation of peripheral vascular resistance by a circulating inhibitor of
      vascular Na/K-ATPase. These two areas merged with the hypothesis that natriuretic
      hormone and the vascular Na/K-ATPase inhibitor were the same factor, and
      furthermore, that this factor played a causative role in the pathophysiology of
      certain types of hypertension. In this communication, the development of this
      field from its beginnings is traced; evidence for the existence of and efforts to
      identify the structure of this factor are briefly reviewed, and suggestions for
      future development of the field are put forward.

PMID- 15970499
TI  - Oocyte-specific gene signaling and its regulation of mammalian reproductive
      potential.
AB  - Oocyte-specific genes play important roles in regulating ovarian development,
      principally through the proper and timely progression of oogenesis and
      folliculogenesis. Development of transgenic mouse models has been critical in
      revealing how oocyte-specific transcripts influence oocyte development and
      growth, integrity of the oocyte-granulosa cell complex, oocyte maturation,
      fertilization, and early embryonic development. Oocyte-derived genes that mediate
      recombination of homologous chromosomes and DNA mismatch repair include Spo11,
      Atm, Dmc1, Msh5, Mlh1, and Msh4. Transcripts such as Dazla and Fig-alpha regulate
      initial proliferation of the primordial germ cell and follicle. Transition from
      the primordial to primary follicle relies on the expression of growth factors
      bFGF, Gdf9 and Bmp15, as well as on the expression of various transcripts that
      mediate oocyte-granulosa cell interactions. Oocyte growth is predominantly under
      exogenous control, however resumption of meiotic progression is dictated by genes
      that influence proper chromatin and spindle regulation, such as Cdk, Histone
      H1oo, Fmn-2, Mad2, and Bub3. Maintenance of meiotic metaphase II arrest prior to
      fertilization is mediated primarily by c-mos, and successful fertilization
      requires the expression of zona pellucida glycoproteins (Zp1, Zp2, and Zp3) and
      Cd9. Following fertilization, maternal-effect and maternally expressed
      'imprinting' genes are necessary for the completion of meiosis and for patterning
      early embryonic development. Recent utilization of suppressive subtractive
      hybridization (SSH), PCR amplification, and cDNA microarray analysis techniques
      alongside established transgenesis models are expanding the classification of
      novel oocyte-specific genes required for reproductive fitness in various species,
      including human.

PMID- 15970500
TI  - Genes related to estrogen action in reproduction and breast cancer.
AB  - Estrogen is an important steroid hormone with diverse functions in different
      parts of the human body. The developmental and physiological role of estrogen is
      mediated by estrogen receptor alpha (ER-alpha) and newly identified ER-beta.
      Regulation of expression of various important cellular oncogenes and tumor
      suppressor genes is a key component of estrogen and ER action. The expression of
      these genes is crucial in various processes such as cell cycle progression,
      mammary gland development, growth factor pathways and apoptosis. A very precise
      and accurate control of these genes is required for normal growth and functioning
      of cells. Aberrant expression of these genes through elevated expression, gene
      amplification or mutation may lead to induction and/or progression of different
      cancers including estrogen-dependent breast cancers. This review briefly
      describes the role of different genes that are regulated by estrogen in female
      reproductive tissues and breast cancer.

PMID- 15970502
TI  - Neuronal function and alpha3 isoform of the Na/K-ATPase.
AB  - The Na/K-ATPase is a complex of integral membrane proteins that carries out
      active transport of sodium and potassium across the cell plasma membrane, and
      maintains chemical gradients of these ions. The alpha subunit of the Na/K-ATPase
      has several isoforms that are expressed in a cell type- and tissue-dependent
      manner. In adult vertebrates, while kidney cells express mostly alpha1, muscle
      and glial cells -- alpha1 and alpha2, and sperm cells -- alpha1 and alpha4
      isoforms of Na/K-ATPase, neurons may express alpha1, alpha2, alpha3 or any
      combination of these isoforms, and evidence suggests that neuronal type is the
      determining factor. The functional significance of multiple isoforms of the Na/K
      ATPase and their non-uniform expression, and the link between neuron function and
      expression of a given isoform of the Na/K-ATPase in particular, remains unknown.
      Several hypotheses on this account were introduced, and in this work we will
      review the present status of these hypotheses, and their standing in application
      to recent data on the expression of isoforms of the Na/K-ATPase in the peripheral
      nervous system of vertebrate animals.

PMID- 15970503
TI  - The NA/K-ATPase and its isozymes: what we have learned using the baculovirus
      expression system.
AB  - The use of the baculovirus expression system for heterologous protein expression
      in insect cells has been of immense value in understanding many different
      structural and functional aspects of the Na/K-ATPase, an enzyme that catalyses
      the active exchange of cytoplasmic Na+ for extracellular K+ across the plasma
      membrane of most cells. The advantage of using insect cells is that they provide
      an eukaryotic expression system able to produce large amounts of active
      recombinant Na/K-ATPase for biochemical studies. In addition, the host cell lines
      commonly used (Sf-9, Sf-21 and High Five) have very little or no Na/K-ATPase,
      offering an environment in which the exogenously expressed enzyme can be studied
      without the interference of the high Na pump background activity common to other
      cells. The present article reviews the advances obtained in the field of the Na/K
      ATPase by using the baculovirus expression system, including the biosynthesis,
      assembly, intracellular trafficking of the alpha and beta subunits of the enzyme,
      their interaction with other proteins, and the structure, function and regulation
      of the various isozymes of the transporter.

PMID- 15970504
TI  - Intron position conservation across eukaryotic lineages in tubulin genes.
AB  - A compilation of intron positions obtained from a large number of eukaryotic
      genomes across orthologous tubulins is explored for molecular evolution.
      Comparison of intron positions for 41 alpha, 80 beta, and 30 gamma tubulin
      genomic sequences indicates that the putative ancestral tubulin gene contained at
      least 19, 33, and 52 intron positions distributed at different sites in the
      coding regions for alpha, beta, and gamma tubulins, respectively. Many intron
      positions are old and are conserved across different eukaryotic lineages and
      intron distribution patterns are consistent with 'introns-early' hypothesis.

PMID- 15970505
TI  - Whole-body interdiction of lengthening of telomeres: a proposal for cancer
      prevention.
AB  - The intrinsic genetic instability of cancer cells makes age-related cancers more
      difficult to postpone or treat than any other age-related diseases. Any treatment
      that a cancer can resist by activating or inactivating specific genes is unlikely
      to succeed over the long term, because pre-existing cancer cells with the
      necessary gene expression pattern will withstand the therapy and proliferate.
      "Whole-body Interdiction of Lengthening of Telomeres" (WILT) is a proposal to pre
      empt this problem by deleting from as many of our cells as possible the genes
      needed for telomere elongation. Cancers lacking these genes can never reach a
      life-threatening stage by altering gene expression, only by acquiring new genes,
      which is far more unlikely. Continuously-renewing tissues can be maintained by
      periodic reseeding with telomere elongation-incompetent stem cells that have had
      their telomeres lengthened in vitro with exogenous telomerase. Here, I describe
      why WILT might prove to be an exceptionally powerful anti-cancer modality.

PMID- 15970506
TI  - Novel testis/sperm-specific contraceptive targets identified using gene knockout
      studies.
AB  - The population explosion and unintended pregnancies resulting in elective
      abortions continue to be the major public health issues in spite of availability
      of current methods of contraception. There is an urgent need for a better method
      of contraception that is accepted, effective, and available. Various targets are
      being investigated that can be used for contraception. The gene knockout
      technology is a powerful approach to identify such novel targets. Using search in
      the database, at least 93 genes were identified in the literature whose deletion
      demonstrated an effect on fertility in male mice. However, majority of these
      knockouts also demonstrated an effect on non-reproductive organs concomitant with
      an effect on fertility. The knockouts of only a few genes/proteins induced a
      specific effect on fertility without a serious side effect. The potential role of
      these novel genes/proteins in contraception/contraceptive vaccine development is
      discussed.

PMID- 15970507
TI  - Gene knockouts that cause female infertility: search for novel contraceptive
      targets.
AB  - The gene knockout technology has revolutionized the fertility/infertility field.
      It has revealed several essential previously undiscovered molecules, new insights
      and novel mechanisms involved in steps of the fertility cascade in females. Using
      database and literature search, knockouts of at least 83 genes were discovered
      that demonstrated an effect on fertility of female mice. These effects ranged
      from abnormality in reproductive structure, ovarian function, oocyte,
      fertilization, embryonic and fetal development, implantation and pregnancy to
      delivery. However, only a few of these knockout of genes such as encoding oocyte
      glycoprotein coat comprised of zona pellucida (ZP) 1, ZP2 and ZP3 and oocute
      plasma membrane specific proteins showed a specific and exclusive target
      infertility effect without concomitant effects on the non-reproductive organ
      system. These molecules will provide novel targets of contraception including
      contraceptive vaccine development.

PMID- 15970508
TI  - Hepatitis C virus (HCV) infection and lymphoproliferative disorders
AB  - Several infectious agents have been associated with development of
      lymphoproliferative disorders. Among these is hepatitis C virus (HCV), which
      infects more than 200 million people worldwide. HCV infection has been linked to
      progression of type II mixed cryoglobulinemia (MC) syndrome and has also been
      suggested to contribute to development of B-cell non-Hodgkin's lymphoma (NHL).
      Mechanisms responsible for development of lymphoproliferative disorders among HCV
      positive patients remain unclear. Accumulating evidence supports a model in which
      chronic stimulation of B-cells by antigens associated with HCV infection causes
      nonmalignant B-cell expansion that may evolve into B-cell NHL. The course of
      disease among HCV-positive B-cell NHL patients may be complicated by coinfection
      with other infectious agents. This possibility has been explored by studies that
      have investigated potential interactions between HCV and human immunodeficiency
      virus (HIV) as well as between HCV and Epstein-Barr virus (EBV). Further
      characterization of the mechanisms by which HCV promotes development of
      lymphoproliferative disorders may improve diagnosis, classification, and
      treatment of these conditions.

PMID- 15970509
TI  - The endogenous ouabain: molecular basis of its role in hypertension and
      cardiovascular complications.
AB  - Elevated levels of the endogenous ouabain (EO), a closely related isomer of
      ouabain, are implicated in rat and human hypertension and in related
      cardiovascular complications. The pathogenetic mechanisms through which EO
      affects the cardiovascular system involve the modulation of the renal Na/K
      ATPase, implicated in renal tubular sodium reabsorption, and the activation of
      signal transduction pathways, promoting the transcription of growth-related
      genes. Experimental and clinical evidence on rats and humans stimulated the
      pharmacological research for developing novel anti-hypertensive agents able to
      antagonize the cellular and molecular alterations mediated by EO. Among them, the
      digitoxigenin derivate, PST 2238, has been selected for its ability to antagonize
      the ouabain-induced effects on blood pressure and organ hypertrophy at oral doses
      of microgram/kg/day in vivo. The pharmacological selectivity and safety of PST
      2238 suggests that the compound may be effective for the treatment of those forms
      of hypertension in which renal sodium handling alterations and cardiovascular
      complications are associated with increased production of EO.

PMID- 15970510
TI  - The toll-like receptor-nuclear factor kappaB pathway in rheumatoid arthritis.
AB  - The study of the role cytokines play in the pathogenesis of rheumatoid arthritis
      (RA) has provided a whole new range of targets for drug development. Many of them
      (e.g. TNF, IL-1, IL-6, IL-15 and IL-18) are already being targeted in the clinic
      with success using neutralizing monoclonal antibodies or soluble cytokine
      receptors. Targeting TNF, in particular, has shown great efficacy in controlling
      both the inflammation and structural damage of the joints, setting a new gold
      standard for the treatment of RA. However, what triggers the production of
      inflammatory cytokines such as TNF in RA remains to be determined. In this
      article, we review evidence suggesting that the transcription factor Nuclear
      Factor kappaB (NF-kappaB) is essential for the expression of both inflammatory
      cytokines and tissue destructive enzymes in RA. Also, we discuss whether Toll
      like receptors (TLRs), major receptors involved in pathogen recognition and
      potent activators of the NF-kappaB pathway, are involved in triggering the
      inflammatory and joint destructive process in RA and whether they constitute
      sensible targets for monoclonal antibodies/soluble receptors and small molecule
      inhibitors. We conclude that although the TLR- NF-kappaB pathway offers ample
      opportunities for therapeutic intervention, future drugs to be approved will need
      to match or exceed the efficacy and safety of anti-TNF agents, with safety the
      most difficult aspect to predict.

PMID- 15970511
TI  - Regulation of adrenocortical cardiotonic steroid production by dopamine and PKA
      signaling.
AB  - There is growing evidence that the adrenal cortex is the source of cardiotonic
      steroid (CS) regulators of sodium, potassium-ATPase (NKA). The control of
      adrenocortical production CS may play a critical role in mediating renal and
      vascular responses involved in arterial hypertension. Dopamine (DA) controls
      renal NKA by direct regulatory phosphorylation and indirectly by modification of
      aldosterone release. In the present studies, Y-1 adrenocortical cell cultures
      which have been shown to produce a cardiotonic steroid indistinguishable from the
      known vertebrate steroid, marinobufagenin (MBG), were treated with various agents
      to stimulate or antagonize dopamine signaling pathways. We demonstrate that Y-1
      cells express both pharmacological types of dopamine receptor (DA1 and DA2).
      Treatment of Y-1 cells with DA stimulated MBG production in a dose range similar
      to that shown to inhibit aldosterone production by the adrenal cortex.
      Experiments with specific DA1 and DA2 receptor agonists and antagonists were
      performed and allowed us to attribute the DA stimulatory effect to a DA1 type
      receptor. The DA stimulatory effect on MBG depended on protein kinase A (PKA) and
      could be blocked by Rp-cAMPS. Although both basal and forskolin-stimulated
      progesterone production by Y-1 cells were profoundly inhibited in Y-1 cell lines
      expressing the dominant negative type I regulatory subunit of PKA, both basal and
      forskolin-stimulated MBG production were demonstrated in these lines. This
      evidence suggests a possible role of DA1 signaling through camp-mediated
      activation of the type II PKA holoenzyme in the adrenal cortex.

PMID- 15970513
TI  - Platelet aggregation: involvement of thrombin and fibrin(ogen).
AB  - Platelets play a key role in hemostasis and thrombosis. The formation of a
      platelet plug is accompanied by the generation of thrombin, which results in the
      generation of fibrin required for stabilization of the platelet plug. Platelet
      plug formation and coagulation are closely linked processes. Thrombin is a potent
      platelet activator, which proceeds through proteolysis of the protease activated
      receptors (PARs). Furthermore, thrombin binds glycoprotein Ib(alpha), which
      amplifies platelet activation by accelerating PAR-1 activation, and possibly also
      by direct signaling events through glycoprotein Ib(alpha). Moreover, thrombin's
      specificity towards other substrates changes after binding glycoprotein
      Ib(alpha). Fibrinogen and fibrin, the end product of the coagulation cascade, are
      also involved in platelet aggregation. Both fibrinogen and fibrin bind the
      integrin alpha(IIb)beta(3), and another fibrin receptor involved in platelet
      aggregation has been postulated. This review will discuss the role of thrombin
      and fibrin(ogen) in platelet functioning, and will highlight pathways at the
      crossroad of coagulation and platelet functioning, which are potential targets
      for antithrombotic therapy.

PMID- 15970512
TI  - IFN-gamma and TNF-alpha inhibit expression of TGF-beta-1, its receptors TBETAR-I
      and TBETAR-II in the corpus luteum of PMSG/hCG treated rhesus monkey.
AB  - The corpus luteum (CL) is a transient endocrine organ that secretes progesterone
      to support early pregnancy. Using in situ hybridization, immunohistochemistry and
      computer imaging analysis, we have investigated the expression of transforming
      growth factor beta 1(TGF-beta 1) , its receptors, type I (TbetaR-I) and type II
      (TbetaR-II) as well as steroidogenic acute regulatory protein (StAR) in the
      corpus luteum (CL) of the rhesus monkey at various stages of CL development. The
      CL was induced by injection of pregnant mare serum gonadotropin (PMSG)/human
      chorionic gonadotropin (hCG). The expression of TGF-beta 1, TbetaR-I and TbetaR
      II as well as StAR was detected in the CL in a time-dependent manner, reaching
      the maximum levels on D10 (functional stage), and decreased on Day 18 (regression
      stage). Injection of interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha
      (TNF-alpha) at the functional stage of CL development significantly decreased the
      expression of StAR, as well as TGF-beta 1, and its receptors TbetaR-I and TbetaR
      II. Our results suggest that TGF-beta 1 and its receptors may play an important
      regulatory role in maintaining CL function, and that IFN-gamma or TNF-alpha is
      capable of inhibiting their expression in the CL.

PMID- 15970514
TI  - Impedance labelless detection-based polypyrrole protein biosensor.
AB  - A simple and sensitive electrochemical immunosensor with impedance labelless
      detection and novel data processing method was investigated. One-step
      copolymerization was used to electrochemically deposit an antibody impregnated
      polypyrrole film on a glassy carbon electrode surface for the immunosensor.
      Impedance measurements provided a labelless or reporterless method to detect
      antibody (Ab)-antigen (Ag) interactions. Dimensionless analysis was employed to
      successfully process the measured impedance data. Since the method derived unit
      impedance change to eliminate or reduce the variation of the bulk electronic
      properties of Ab/polypyrrole films, the signal to noise ratio (S/N) was
      significantly improved for high sensitivity and specificity. Nonspecific binding
      effect was studied by array electrode chips and was found out that the
      polypyrrole electrode without antibody attachment had much stronger nonspecific
      binding effect than the Ab/polypyrrole electrode; incubation followed by
      thoroughly washing significantly reduced the nonspecific interference. 10 pg/ml
      detection limit and superior specificity were achieved by the method,
      demonstrating a highly sensitive labelless immunosensor in comparison with the
      detection limit of ng -microgram/ml for the reported polypyrrole based
      immunosensors. The electrochemical immunosensors presented in this paper, due to
      its simplicity, low cost, high sensitivity and superior specificity, could be an
      invaluable tool for clinical diagnostics and could have potential applications in
      drug discovery, environmental and food analysis.

PMID- 15970515
TI  - Type II vanilloid receptor signaling system: one of the possible mechanisms for
      the rise in asthma cases.
AB  - The prevalence of asthma keeps on increasing worldwide, especially in western
      societies over last 40 years. The mechanism of asthma is unclear. Recently,
      concern about indoor air pollution as a risk factor for asthma has been arisen.
      In present study, 25 Kun Ming male mice were placed in an air chamber containing
      respective formaldehyde (FA) concentration of 0, 0.5, 1.0, 3.0 mg/m3,and 3.0
      mg/m3 with Capsazepine (CPZ, a specific antagonist of vanilloid receptor)
      pretreatment in five testing groups (n=5 per group) for inhale experiments. The
      inhaled groups were exposed to gaseous FA for 6 hours each day in 10 successive
      days. After exposure, the concentrations of IL4 in blood serum and broncho
      alveolar lavage fluid (BALF) were measured. Experimental results showed that the
      IL4 level in serum was too low to be detected; and the concentrations of IL4 in
      BALF increased in a dose-dependent manner. However, for the CPZ-pretreated group
      the IL4 level in BALF decreased significantly (compared with 3.0 mg/m3 FA inhaled
      group, p<0.01). This paper describes experimental animal methods to probe IL4
      level, an important indicator for IgE response. The studies in this paper
      indicated that gaseous FA might induce acquired atopy by type II VR1 signaling
      system. These findings suggested that indoor air pollutants such as FA might be
      key risk factors for the rise in asthma cases, and type II VR1 signaling system
      might be one of the mechanisms for the rise.

PMID- 15970516
TI  - Characterization of alpha-enolase as an interferon-alpha 2 alpha 1 regulated
      gene.
AB  - Interferons (IFNs) are multifunctional cytokines that after binding to the cell
      surface receptor induce the expression of a large number of genes, which in turn,
      mediate many biological processes including host defense, cell growth control,
      signaling, and metabolism. Here we show that IFN-alpha activates the mitogen
      activated protein kinases (MAPK) ERK1/2 and the transcription factor CREB/ATF-1,
      which lead to the alpha-enolase (alpha-ENO) gene expression in fibroblasts. Alpha
      ENO mRNA accumulation was apparent 6 h post-IFN stimulation and required both de
      novo protein synthesis and active gene transcription, which is typical of a
      secondary response gene. Alpha-ENO expression does not appear to be restricted to
      fibroblasts, since it was equally verified in peripheral blood mononuclear cells
      (PBMC). Furthermore, IFN-alpha stimulates the expression of the primary response
      genes c-fos and egr-1, which was followed by an increase in DNA binding activity
      of c-FOS and EGR-1 proteins, as verified by shift assays using the cis-acting
      elements AP-1 and EGR-1 localized at the alpha-ENO promoter. Finally, we also
      demonstrated that IFN treatment of PBMC cause an increase in both, alpha-ENO
      expression on the cell surface and plasmin generation followed addition of
      exogenous plasminogen.

PMID- 15970517
TI  - Advances in understanding adenosine as a plurisystem modulator in sepsis and the
      systemic inflammatory response syndrome (SIRS).
AB  - Adenosine is a ubiquitous molecule that influences every physiological system
      studied thus far. In this review, we consider the influence of this purine
      nucleoside on some of the physiological systems affected during sepsis and SIRS.
      In the control of perfusion and cardiac output distribution, endogenous adenosine
      appears to play an important role in regulating perfusion in various vascular
      beds. Some of this control is mediated by stimulation of adenylyl cyclase, while
      part occurs by stimulating the production of nitric oxide. In the heart,
      adenosine may act as an inhibitory modulator of TNF-alpha expression. With regard
      to innate immune responses the effects of adenosine vary considerably, and are
      complex. However, the dominant responses relevant to SIRS indicate attenuation of
      inflammatory responses. Many of the effects of adenosine may also involve
      modulating oxyradical-mediated response. This occurs via increased oxyradical
      production via adenosine degradation (xanthine oxidase pathway), or limiting
      inflammatory oxyradical generation. Attempts to exploit the beneficial responses
      to adenosine have met with some success, and are considered here.

PMID- 15970518
TI  - Docetaxel induces p53-dependent apoptosis and synergizes with farnesyl
      transferase inhibitor r115777 in human epithelial cancer cells.
AB  - Docetaxel (Taxotere, DTX) is a promoter of apoptosis in cancer cells. Since
      cytotoxic mechanisms of DTX are not yet fully understood, we have investigated
      the effects of DTX on apoptosis and ras-->Erk-mediated signal transduction in
      human epidermoid KB, colon HT-29 and breast HCC1937 cancer cells. We have found
      that the exposure to 0.78 or 1.56 or 2.5 ng/ml DTX for 48 h induced apoptosis and
      growth inhibition in about 50 % of KB, HCC1937 and HT-29 cell population,
      respectively. In these experimental conditions, PARP and caspase 3 cleavage was
      also showed in all cell lines. KB and HCC1937 cells express a wild type p53 while
      HT-29 display a mutated form. Interestingly, we have found that DTX reduces the
      expression of mutated p53 in HT-29 and increases the expression of wild type in
      KB and HCC1937 cells. Moreover, DTX reduces ubiquitination of the wild type p53
      in KB and HCC1937 cells and increases the ubiquitin-conjugated form of mutated
      p53 in HT-29 cells. Furthermore, exposure of cancer cells to DTX for 48 h
      increases the expression and activity of Ras and up-regulates Raf-1 and the
      phosphorylated isoforms of Erk-1/2. On the bases of these data, we have
      hypothesized that the increased activity of the ras-->erk-dependent pathway
      induced by DTX could be a protective signalling from the apoptosis caused by the
      drug. Therefore, we have used R115777, a farnesyl transferase inhibitor that
      inactivates ras, in combination with DTX. The combined treatment with DTX and
      R115777 resulted in a strong synergism in growth inhibition in the three cell
      lines. These data suggest the use of the combination in these therapeutic
      settings even if further experiments are required for the clinical translation.

PMID- 15970519
TI  - Human genome -- from pieces to patterns.
AB  - A profile of exon-intron lengths in genes shows a normal distribution. This
      observation suggests that different genes may have portions of their total exon
      and/or intron lengths in common. In order to explore the common exon-intron
      structural patterns that may arise due to common lengths across genes, we
      compared the exon-intron length patterns of annotated human genes. We discovered
      1762278 conserved arrangements of exon-intron length across the otherwise
      unrelated and diverse genomic landscape. The existence of common exon-intron
      length patterns across unrelated genes suggests for their role of in gene
      assemblage and human genome design and architecture.

PMID- 15970520
TI  - Ox-LDL plays dual effect in modulating expression of inflammatory molecules
      through LOX-1 pathway in human umbilical vein endothelial cells.
AB  - Lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) has been
      recognized to be the major endothelial receptor for oxidized low-density
      lipoprotein (ox-LDL). Ox-LDL has been reported to induce the expression of
      inflammatory adhesive molecules from vascular endothelium. However, the mechanism
      of this action has not been fully elucidated. Peroxisome proliferation-activated
      receptor-gamma (PPARgamma) regulates the expression of inflammatory adhesive
      molecules. The present study was carried out to investigate the role of LOX-1
      PPARgamma pathway in regulating expression of adhesion molecules, ICAM-1 and E
      selectin in HUVECs. Ox-LDL increased the expression of ICAM-1 and E-selectin in a
      concentration (10-50 microg/ml)--and time (6-36 hours)--dependent manners. These
      effects were significantly inhibited by pretreatment of HUVECs with polyinosonic
      acid or carrageenan. Preincubating HUVECs with 15d-PGJ2 attenuated the expression
      of ICAM-1 and E-selectin in response to ox-LDL, although ox-LDL stimulated the
      expression of PPARgamma. Upregulation of ICAM-1 and E-selectin mediated by ox-LDL
      were inhibited more significantly by the combination of 15d-PGJ2 and polyinosonic
      acid as compared to either 15d-PGJ2 or polyinosonic acid alone. The results
      suggested that ox-LDL through its receptor LOX-1 promotes pro-inflammation
      response by increasing expression of ICAM-1 and E-selectin, simultaneously
      activates PPARgamma triggering cellular anti-inflammation response in protection
      from the inflammation lesions in HUVECs.

PMID- 15970521
TI  - Atypical antipsychotics produce within-session decrements on self-stimulation of
      the rat medial prefrontal cortex.
AB  - It has been described that "typical" antipsychotic drugs (APDs) induce
      characteristic within-session response decrements in operant behaviors, including
      intracranial self-stimulation (ICSS). In contrast, recent reports have shown that
      in food operant behavior, clozapine and a number of "atypical" APDs do not give
      rise to within-session effects. However, to elucidate whether or not this is a
      common property of atypical APDs, their effects on other operant models need to
      be studied. To address this question we investigated the temporal pattern of ICSS
      responding, after systemic administration of five atypical APDs and the typical
      antipsychotic, haloperidol. Rats were trained to lever press for electrical
      stimulation at the medial prefrontal cortex (mPFC), and response rates were
      recorded during each 3-min period of the 15-min session. Significant within
      session response decrements on mPFC ICSS were observed with haloperidol,
      risperidone, sertindole and olanzapine but not with clozapine or ziprasidone. The
      magnitude of within-session decline produced by the APDs tested was positively
      correlated with their affinity for dopamine D2 receptors. The results show for
      the first time that atypical APDs are capable to induce within-session decrements
      on ICSS behavior, and suggest that this particular temporal pattern of responding
      is not exclusively characteristic of typical APDs. The results are also
      consistent with the hypothesis that the ability of APDs to induce greater within
      session effects may be related, in part, to potent D2 antagonism.

PMID- 15970522
TI  - The gamma subunit of Na/K-ATPase: an exceptional, small transmembrane protein.
AB  - The gamma subunit has been characterized as a fine-tuning modulator of the Na/K
      ATPase expressed in kidney tissues. This small single transmembrane domain
      protein interacts with the alpha subunit of Na/K-ATPase to increase affinity for
      ATP and decrease affinity for Na allowing medullary cells to continue pump
      activity under reduced cellular ATP levels. The gamma subunit is undetectable in
      kidney cell cultures grown under isotonic conditions and expression is induced
      with acute or chronic exposure to hypertonicity. The gamma subunit demonstrates
      remarkable regulatory complexity including induction by chloride ions rather than
      sodium, the differential expression of at least 2 isoforms, involvement of
      separate MAP kinase signaling pathways for transcription (JNK) and translation
      (PI3K) as well as cell type regulation of expression. Mutation in the
      transmembrane domain of the gamma subunit has been implicated in cases of primary
      hypomagnesemia. Alternative roles have been established for the gamma subunit in
      embryonic development and quite possibly additional functions in cell signaling
      as yet unrecognized may be possible.

PMID- 15970523
TI  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in breast
      cancer: current status and future development.
AB  - Evidence suggests that the epidermal growth factor receptor (EGFR) and its
      ligands are involved in the pathogenesis of different human carcinomas, including
      breast cancer. Results of phase II clinical trials of EGFR tyrosine kinase
      inhibitors (TKIs) have shown that these compounds have little activity in breast
      cancer patients when used as single agents. The potential pitfalls of these
      clinical trials, and the molecular mechanisms that might be involved in
      regulating the sensitivity/resistance of breast cancer cells to EGFR TKIs are
      discussed in this brief article. In particular, preclinical findings clearly
      demonstrate that breast cancer cells are able to activate different mechanisms to
      escape the anti-tumor effects of drugs directed against growth factor-driven
      pathways. Therefore, it is conceivable that significant blockade of tumor growth
      might be obtained only through contemporary blockade of different growth
      promoting pathways, at least in advanced disease. In addition, preclinical and
      clinical findings support the use of EGFR TKIs in specific subgroups of breast
      cancer patients, such as estrogen receptor positive (ER+), tamoxifen resistant
      patients. In this regard, we describe potential future applications of these
      compounds in combination with other agents in the treatment of breast carcinoma.

PMID- 15970524
TI  - Sentinel node biopsy: concepts and current status.
AB  - One of the major routes for spread of cancer is via lymphatic vessels to local
      lymph nodes. For this reason, local lymph nodes are removed to prevent further
      spread of tumors. Over the years, surgery has evolved from therapeutic
      lymphadenectomy for involved nodes to elective lymphadenectomy when the risk of
      harboring metastasis was high. Two major problems encountered with such an
      approach included the morbidity of the procedure and a high proportion of nodes
      being negative on pathologic examination. For these reasons, a new approach has
      been developed -- Sentinel node biopsy (SNB). SNB is an in vivo assessment of the
      nodal involvement in early disease. During surgery, the sentinel node is
      identified by the injection of a blue dye, a radio-colloid substance or both
      which has been show to have fewer false negatives. This procedure is now
      standardized during surgery of breast carcinoma or melanoma. However, its use in
      other types of tumors is still considered investigational at present.

PMID- 15970525
TI  - Chemotherapy and novel therapeutic approaches in malignant glioma.
AB  - Glial neoplasms represent 0.5-1% of all cancers in most Western countries.
      Malignant gliomas are among the most devastating cancers, leading to death in
      most cases. They present unique challenges due to their location, aggressive
      biological behavior and diffuse infiltrative growth. Notwithstanding the
      development of new surgical and radiation techniques in the last thirty years, a
      cure for malignant gliomas remains elusive. In this article, we will review the
      standard and new therapies used for malignant gliomas. As standard therapies,
      surgery, radiation therapy and systemic chemotherapy, are in a continuous process
      of evolution. Multiple chemotherapies have been used in malignant gliomas, as
      single agents, in combination, or with different modes of administration,
      including high-dose chemotherapy with stem cell rescue and intra-arterial
      chemotherapy. The last decade has been noticeable for the advent of a better
      understanding of the biology of malignant gliomas. This has stimulated active
      research in multiples areas and the advent of new treatment strategies.
      Techniques to circumvent the resistance mechanisms to chemotherapy have been
      evaluated, tyrosine kinase inhibitors have shown activity in malignant primary
      brain tumors and radioimmunotherapy remains an area of active research. In this
      article, we review the past, present and future treatments of malignant gliomas
      with a special interest on chemotherapy, resistance mechanisms and tyrosine
      kinase inhibitors.

PMID- 15970526
TI  - Functional grouping of yeast genes via biclustering microarray data.
AB  - Biclustering algorithm on Gibbs sampling strategy is a recruit in the field of
      the analysis of gene expression data of microarray experiments. Its feasibility
      and validity still need to be researched not only for synthetic datasets but also
      for real datasets. Here we investigated a biclustering algorithm on a microarray
      dataset of Yeast genome through building a database for storing microarray
      datasets and MIPS data, and running the scripts on Matlab platform to discover
      gene patterns. In contrast with standard clusterings that reveal genes behaving
      similarly over all the conditions, biclustering groups genes over only a subset
      of conditions for which those genes have a sharp probability distribution. It has
      the key advantage of providing a transparent probabilistic interpretation of the
      biclusters. Its basic strategy of Gibbs sampling does not suffer from the problem
      of local minima that often characterizes expectation maximization, so that the
      patterns should be more global and accurate. Also we tested it with the known
      explanation of genes in MIPS, objectively to demonstrate the effectiveness and
      deficiencies of biclustering approach, and the functions of a few unknown ORFs in
      some bicluster can be deduced in the present research. In addition, the result of
      similarity searching in Blast-Search can be an assistant evidence for its
      effectivity.

PMID- 15970527
TI  - The recognition pattern of gammadelta T cells.
AB  - The main function of immune system is to recognize and respond to foreign
      antigens. During the course of evolution, the body has successfully developed
      four kinds of mechanisms to recognize antigens, including pattern recognition
      mediated by macrophages, missing-self and induced-self recognition for NK cells,
      antigen specific recognition for alphabeta T cells and B cells and "broad
      spectrum specific" recognition for gammadelta T cells. The three formers have
      made great progress these years. However, details of antigen recognition by
      gammadelta T cells are still mysterious. Gammadelta T cells, a class of T cells
      only existing in primates, differ from alphabeta T cells in TCR diversity, the
      structure of TCR-CD3 complex, the tissue distribution, the antigens that they
      recognize and the way involved in recognition. Here, we shed light on the
      recognition mechanism of gammadelta T cells against several known antigens and
      discuss the possible response pattern along the research historical process. We
      put forward a recognition hypothesis for gammadelta TCR that is conformational
      recognition based on germline encoded recognition. The key germline encoded amino
      acids dominate the "putative binding box" and are responsible for recognition.
      Meanwhile, after gammadelta T cells are activated, several other molecules such
      as CD69, CD16, 2B4, NKG2D also participate in inducing cytotoxicity of activated
      gammadelta T cells. Obviously, the illustration of recognition mechanism for
      gammadelta T cells will help to comprehensively understand the whole immune
      system and design the higher effective multi-epitope vaccines for tumor and
      infection immunity.

PMID- 15970528
TI  - ISG15: a ubiquitin-like enigma.
AB  - ISG15 is a 17 kDa protein encoded by an interferon stimulated gene. Described in
      1979, it was the first ubiquitin-like modifier to be identified, and its
      discovery followed the first reports of ubiquitin by only four years. While many
      important functions for ubiquitin have been reported, the functions for ISG15 and
      its conjugation are still largely unknown. Evidence suggests that ISG15 and its
      modification system play important roles in the innate immune response,
      regulation of interferon signaling, pregnancy, and several cancers. Modification
      of proteins by ISG15 occurs in a manner similar to that of ubiquitin and other
      ubiquitin-like modifiers. The enzymes which help perform the activation and
      conjugation of ISG15 have recently been identified. The conjugation enzyme
      identified for ISG15 was revealed to be an enzyme that was also involved in
      ubiquitin conjugation. Identification of an ISG15 specific protease has also been
      reported. Knockout of this protease in mice decreases the lifespan of these mice
      and makes them hypersensitive to treatment with interferon or lipopolysaccharide.
      The study of ISG15 and its modification system may yield a set of potentially
      useful therapeutic targets and thus, there is an increasing awareness and
      interest in this protein modifier. This review will highlight the history of its
      discovery, describe more recent observations about the enzymes involved in ISG15
      modification, and summarize new findings which have important implications for
      the ISG15 system in signal transduction and immunology. This review will also
      point out important questions that remain to be answered and identify the major
      roadblocks which currently obstruct the understanding of ISG15 biologic
      functions.

PMID- 15970529
TI  - Vitamin D and cancer: an update of in vitro and in vivo data.
AB  - 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, Calcitriol) is a pleiotropic hormone
      with anti-proliferative, pro-apoptotic and pro-differentiation effects on
      numerous cell types, which suggest anti-cancer activity in addition to its
      classical regulatory action on calcium and phosphate metabolism. 1,25(OH)2D3
      exerts its actions mainly via its high affinity receptor VDR through a complex
      network of genomic (transcriptional and post-transcriptional) and also non
      genomic mechanisms, which are partially coincident in the different cells and
      tissues studied. Epidemiological and experimental in vitro and in vivo data
      support a cancer preventive role of 1,25(OH)2D3. The anti-cancer activity of
      1,25(OH)2D3 and multiple analogs with reduced calcemic properties, which are thus
      less toxic, is under investigation in a long list of cultured cell types and in
      several in vivo models of wild-type and genetically-modified animals. Some
      vitamin D compounds have reached clinical trials, but results are still scarce.

PMID- 15970530
TI  - Inflammation-dependent thrombosis.
AB  - Vessel wall endothelial damage initiates a local inflammatory response, which
      promotes a prothrombotic state driven by tissue factor, adhesion molecules, and
      pro-inflammatory cytokines. Understanding how natural inflammatory mechanisms
      promote a procoagulant state, may lead to the development of new pharmacological
      interventions targeted at thrombosis.

PMID- 15970531
TI  - Gene therapy for erectile dysfunction.
AB  - The past decade has seen an explosion of new information on the physiology of
      penile erection, pathophysiology of erectile dysfunction (ED), and development of
      new oral agents (e.g., three PDE5 inhibitors) to manage ED. Although all three
      selective PDE5 inhibitors are effective in the majority of ED cases, these oral
      medications have failed in certain disease states, such as diabetic ED,
      postprostatectomy ED, and severe veno-occlusive dysfunction. Only about 50% to
      60% of these cases benefit from PDE5 inhibitor therapy, prompting the development
      of new approaches, including gene-based therapies for the treatment of ED. The
      penis is a convenient tissue target for gene therapy because of its external
      location and accessibility, the ubiquity of endothelial lined spaces, and low
      level of blood flow, especially in the flaccid state. Initially, gene therapy has
      been reserved for the treatment of life-threatening disorders including cancer,
      hereditary and acquired diseases. However, gene therapy is an attractive
      therapeutic possibility for the treatment of ED. Evolution of nitric oxide (NO),
      a small gaseous, lipophilic signaling molecule that is produced by nitric oxide
      synthase (NOS) activates guanylate cyclase (GC), resulting in increased cyclic
      guanosine monophosphate (cGMP) production, plays a significant role in our
      understanding of cavernosal smooth muscle physiology. Many gene therapy
      strategies have focused on the NO/GS/cGMP pathway. All three NOS isoforms,
      endothelial NOS (eNOS), neuronal NOS (nNOS), and iNOS have been used for gene
      therapy in order to modulate erectile response. Various viral and nonviral
      vectors have been used to date for the transfer of genetic material to the target
      cell or tissues with various degrees of success. Recently, second generation or
      "gutless" (helper-dependent) adenovirus vectors have been developed in order to
      reduce cellular toxicity and immune response, while increasing efficient gene
      therapy. Varieties of other gene therapy trials have also been undertaken for the
      treatment of ED and are the focus of this review.

PMID- 15970532
TI  - Electrochemical activation of glucose oxidase with a 140-fold enhancement in
      intramolecular electron transfer rate constant.
AB  - In this work, we describe the electrochemical activation of glucose oxidase (GOx)
      via covalent attachment of a novel redox mediator, Os(bpy)2(API)Cl (bpy = 2,2'
      bipyridine, API = 3-aminopropylimidazole), to the peptide backbone of GOx
      targeting at aspartate and glutamate residues. Cyclic voltammetry showed a pair
      of well-defined voltammetric peaks centered at 0.11 V for the activated enzyme.
      Os(bpy)2(API)Cl promotes direct oxidation of FADH2 centers in GOx without the
      need of any mediating agents in solution. Amperometric tests in glucose solution
      revealed that the GOx retains its enzymatic activity toward the oxidation of
      glucose. An intramolecular electron transfer rate constant of 1.0x10(5) s(-1) was
      obtained for the activated GOx, compared with the rate constant of 7.0x10(2) s(
      1) of the natural GOx-oxygen system, making this an amenable system for biosensor
      applications. Attempts were made in utilizing the activated GOx as an
      electrochemical tag in nucleic acid assay.

PMID- 15970533
TI  - Cross talk of signaling and apoptotic cascades in the CNS: target for virus
      modulation.
AB  - Signaling cascades that regulate proliferation, differentiation and apoptosis
      determine cell life and death decisions. All are targets of virus modulation.
      These cascades are briefly described in this review, underscoring cross talk and
      the integration of distinct signals that contribute to central nervous system
      (CNS) disease.

PMID- 15970534
TI  - Herpes simplex virus type 2 encodes a heat shock protein homologue with apoptosis
      regulatory functions.
AB  - The decision to undergo apoptosis lies in the balance between pro- and anti
      apoptotic proteins. Since virus replication relies on the cellular machinery,
      viruses have evolved various strategies to alter this balance. They target the
      Bcl-2 and signaling protein kinase (PK) apoptosis modulatory families by encoding
      homologues or altering the expression of the cellular proteins. The heat shock
      proteins (Hsp) are emerging as a new family of apoptosis modulatory proteins and
      are also a target of virus modification. Hsp function in protein folding and
      activation, often assisted by co-chaperones. They complex with nascent or damaged
      proteins and chaperone them for refolding and resumption of function, or for
      proteosomal degradation. Until recently, Hsp were considered strictly anti
      apoptotic, possibly by virtue of their contribution to the removal of damaged and
      undesirable client proteins. However, recent studies have also begun to associate
      the Hsp with pro-apoptotic functions. Herpes simplex virus type 2 (HSV-2) encodes
      two proteins homologous to Hsp family members. One of these, known as ICP10PK, is
      a homologue to a newly cloned Hsp (H11) and modulates virus-induced apoptosis.
      ICP10PK is unique among the viral proteins that regulate apoptosis in that it
      targets all the families of apoptosis modulatory proteins. It activates the ERK
      signaling pathway, stabilizes Bcl-2 and upregulates Hsp70 and Hsp27 as well as
      the Hsp70 co-chaperone Bag-1. Its ability to commander these families of
      apoptosis regulators is required for HSV-2 replication and latency
      establishment/reactivation.

PMID- 15970535
TI  - Virus signaling and apoptosis in the central nervous system infection.
AB  - Viruses target the central nervous system (CNS) incidentally, due to
      complications of systemic infection, or specifically, by ascending via the axons
      of peripheral and cranial nerves. In the CNS, viruses cause acute disease (viz.
      encephalitis), latent infections or neurodegenerative pathology. Causation of
      acute disease or immune-mediated pathology, and virus involvement in the etiology
      of chronic neurodegenerative diseases depends, at least in part, on the ability
      to commander signaling pathways. Better understanding of these virus-host cell
      interactions will help identify molecular targets for the development of improved
      therapeutic strategies.

PMID- 15970536
TI  - The herpes simplex virus type 2 protein ICP10PK: a master of versatility.
AB  - Herpes simplex viruses types 1 (HSV-1) and 2 (HSV-2) are associated with a wide
      range of diseases related to infection of epithelial or neuronal tissues. The two
      viruses evidence distinct pathogenesis aspects, which are likely mediated by
      distinct viral genes. One such gene is UL39, which codes for the large subunit of
      ribonucleotide reductase (R1, also known as ICP6 and ICP10 for HSV-1 and HSV-2
      respectively). The HSV-2 R1 has serine-threonine protein kinase (PK) activity,
      which is located within the first 411 amino acids (ICP10PK). ICP10PK is a
      constitutively activated growth factor receptor (GFR) that signals through the
      Ras/MEK/ERK pathway. It has transforming activity in immortalized cells,
      mitogenic (but not transforming) activity in normal diploid cells, and anti
      apoptotic (survival) activity in post mitotic neurons in the central nervous
      system (CNS). In addition to the Ras/MEK/ERK, ICP10PK also activates the PI3
      K/Akt pathway, upregulates the Ras family member Rap-1 and adenylate cyclase and
      activates the B-Raf kinase activity. ICP10 PK appears to have a cellular origin.
      Its conservation is most likely to reflect the ability to impart an evolutionary
      advantage, particularly in the face of pro-apoptotic viral genes. Indeed,
      activation of the Ras/MEK/ERK pathway by ICP10PK is required for virus growth.

PMID- 15970537
TI  - Defects in ankyrin-based cellular pathways in metazoan physiology.
AB  - Ankyrins are a ubiquitously expressed family of membrane-adaptor proteins found
      in most vertebrate tissues. Since the first ankyrin polypeptide was identified
      over 25 years ago, studies in humans, mice, and lower organisms have implicated
      critical roles for ankyrins in normal metazoan physiology. This review will
      provide an overview of the ankyrin family and highlight seminal findings in the
      field which have linked dysfunction in ankyrin-based pathways with defects in
      metazoan physiology and human disease.

PMID- 15970538
TI  - Fabrication of a hydrogen peroxide biosensor based on a self-assemble composite
      oxide film.
AB  - A titania film with horseradish peroxidase (HRP) was immobilized on indium tin
      oxide (ITO) electrodes to act as a biosensor of hydrogen peroxide via the self
      assembling and sol-gel route. The film was characterized by the atomic functional
      microscopy, electrochemical and UV-vis spectroscopy methods. The resulting
      biosensor exhibited fast amperometric response and good stability to hydrogen
      peroxide (H2O2). The linear range for H2O2 determination was from 2 x10(-6) to
      1.45 x 10(-3) M, with a detection limit of 4 x10(-6) M based on S/N=3. The
      apparent Michaelis-Menten constant of the biosensor to H2O2 was estimated to be
      1.5 mM, showing the HRP on the films had the higher biologic activities.

PMID- 15970539
TI  - Efficient probe immobilization on poly (dimethylsiloxane) for sensitive detection
      of proteins.
AB  - Chemical surface modification methods were investigated to activate surface of
      poly-(dimethylsiloxane) (PDMS) for probe immobilization in enzyme-linked
      immunosorbent assay (ELISA). The investigations started from dramatization of
      PDMS surface with (3-aminopropyl)-triethoxysilane (APTES). Amino groups generated
      by APTES were either derived into carboxyl group by Succinic acid anhydride
      (SAA), then captured the protein through the heterobifunctional cross-linker, 1
      ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), or directly
      reacted with homobifunctional cross-linker, glutaraldehyde (GA). Rabbit IgG, Goat
      IgG, Human IgA and Rat IgG were covalently immobilized on PDMS by both methods,
      and examined through well-organized competitive inhibition ELISA. The results
      demonstrated that both GA and EDC based methods had good covalent immobilization
      capability, and the EDC method had higher efficiency than the GA method. The
      competitive ELISA with probe immobilization through EDC had a detection limit of
      pg/ml level. The method was proved to be applicable for immobilization of
      different proteins. The topography of the immobilized protein properties was
      studied by atomic force microscope (AFM), demonstrating that the immobilization
      by GA had protein conglomeration, resulting in poorer uniformity and lower
      immobilization efficiency than EDC method. The possible reason is protein inter
      molecule crossing linkage by the homobifunctional group of GA. Due to its
      simplicity, low cost, and high immobilization efficiency, EDC based
      immobilization method could provide great potential for making ELISA protein
      chips based on PDMS.

PMID- 15970540
TI  - Role of B7-H1 and B7-H4 molecules in down-regulating effector phase of T-cell
      immunity: novel cancer escaping mechanisms.
AB  - The majority of human and rodent cancers display various antigens which could
      elicit cellular and humoral immune responses. Such immunity, however, often fails
      to prevent progressive growth of cancers. It has long been speculated that tumor
      antigens may not be presented in appropriate fashion, which subsequently fails to
      elicit a strong immune response. Recent studies, however, indicate that
      immunization by formulated tumor antigens or even transfer of pre-activated T
      lymphocytes also have limited impact on cancer growth despite the fact that these
      methods could often enhance immune responses in cancer patients. These findings
      imply that even afferent arm of immunity are strengthen, it is not necessarily
      being translated to tumor regression. It is possible that the development of
      evasion mechanisms in tumor microenvironment play a critical role in the
      resistance of therapeutic immune responses. Recent studies provide compelling
      evidence that human and rodent cancers develop evasion mechanisms by aberrantly
      expressing normal proteins, which are required for normal tissue homeostasis, to
      either build a microenvironment locally or reach other organs systemically. In
      this review, we will focus our discussion on two recently described molecules, B7
      H1 and B7-H4, in the context of their roles in the evasion of tumor immunity and
      possible approaches for therapeutic manipulation.

PMID- 15970541
TI  - Dendritic cell vaccines and immunity in glioma patients.
AB  - The dismal prognoses suffered by malignant primary brain tumor (glioma) patients
      remain unchanged over the past two decades despite significant improvements in
      the treatment of distinct tumors. Immunotherapy, and vaccine therapy in
      particular, represents a promising experimental approach to treat malignant
      gliomas, but major challenges still remain to render vaccination clinically
      effective. These challenges include diminishing the risk of pathologic
      autoimmunity, and identifying the cellular basis of clinical vaccine benefits.
      Addressing such challenges should eventually help increase the proportion of
      patients experiencing clinical vaccine benefits. Recent studies in glioma
      patients have characterized tumor antigens on human gliomas, identified some of
      the immune cells involved in beneficial anti-glioma immunity, and examined how
      gliomas may be altered by sub-lethal immune influences. This has provided a
      glimpse of the strength to which immunity influences glioma clinical outcome, and
      resurrects hope that clinically effective vaccines to treat these tumors is
      within reach. Insight into the complex dynamics of immune-tumor interactions
      promises to extend this reach by delineating mechanisms of immune synergy with
      other forms of treatment.

PMID- 15970542
TI  - Biology of Kaposi's sarcoma-associated herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) is
      a newly identified herpesvirus. KSHV is an important pathogen capable of causing
      disease that affects all age groups worldwide. KSHV is etiologically associated
      with all forms of Kaposi's sarcoma (KS), body cavity lymphomas, and multicentric
      Castleman disease (MCD). The use of highly active antiretroviral therapy (HAART)
      since 1996 has markedly reduced the prevalence of KS in western countries, but
      because 99% of the 40 million patients with AIDS in the world cannot afford
      HAART, KSHV pathogenesis is still a very common problem. In this chapter, we
      delineate some of the latest findings about KSHV infection and pathogenesis.

PMID- 15970543
TI  - Androgen metabolic genes in prostate cancer predisposition and progression.
AB  - Significant evidence implicates androgens in prostate cancer etiology. We review
      recent data with regard to the association between several allelic variants of
      specific androgen-metabolic genes and the predisposition to prostate cancer. We
      also review the emerging evidence regarding the role of genetic variants of these
      genes as well as the androgen receptor in prostate cancer progression. Based on
      the prostate cancer paradigm, we propose that a multidisciplinary attack on the
      problem--involving biochemistry, genetics, pharmacogenetics, endocrinology and
      molecular epidemiology--may be important for the understanding and successful
      treatment of complex (in terms of etiology) human diseases.

PMID- 15970544
TI  - Modeling gene expression in the mouse uterine horn by in vivo adenovirus-mediated
      gene delivery.
AB  - Endometrium is a unique tissue that is prepared for implantation of blastocyst
      during each menstrual cycle by expression of genes during a defined period of
      endometrial receptivity. Induction of gene over-expression in endometrium allows
      gaining insight on the role that genes play in endometrial function. Here, we
      show that induction of a state of gene over-expression in endometrium is feasible
      by in vivo gene delivery by transduction with adenovirus. Analysis of endometrium
      following adenoviral transduction of LacZ showed increased beta-galactosidase
      activity in endometrial glands as early as 24 hours following in vivo gene
      transfer. By 72 hour, the expression was uniformly strong throughout the uterine
      horn. Viral transduction was efficient in the range of 0.24-24x10(8) pfu (4.8
      480x10(8) particles) in normal, pregnant and decidualized mouse uterine horns.
      These findings show that induction of a state of gene over-expression can be
      successfully attained in endometrium by adenoviral gene delivery.

PMID- 15970545
TI  - T cell immunity in patients with malignant glioma: recent progress in dendritic
      cell-based immunotherapeutic approaches.
AB  - Despite dramatic advances in surgical technique, imaging, and adjuvant
      radiotherapy or chemotherapy, the prognosis for patients with malignant glial
      tumors remains dismal. Based on the current knowledge regarding immune responses
      in the healthy central nervous system (CNS) and glioma-bearing hosts, we discuss
      dendritic cell (DC)-based immunotherapeutic approaches for malignant gliomas and
      the relevance of recent clinical trials and their outcomes. It is now recognized
      that the CNS is not an immunologically tolerated site, and clearance of arising
      glioma cells is a routine physiological function of the normal, non-compromised
      immune system. To escape from immune surveillance, however, clinically apparent
      gliomas develop complex mechanisms that suppress tumoricidal immune responses.
      Although the use of DCs for the treatment of glioma patients may be the most
      appropriate approach, an effective treatment paradigm for these tumors may
      eventually require the use of several types of treatment. Additionally, given the
      heterogeneity of this disease process and an immune-refractory tumor cell
      population, the series use of rational multiple modalities that target different
      tumor characteristics may be the most effective therapeutic strategy to treat
      malignant gliomas.

PMID- 15970546
TI  - Stromal responses in human primary melanoma of the skin.
AB  - Tumour development and progression has long been considered as the consequence of
      an imbalance between apoptosis and proliferation of transformed cells. However,
      whereas genetic aberrations leading to the activation of oncogenes and/or loss of
      tumour suppressor genes are crucial for the transformation towards aberrant cell
      growth, progression towards a full blown malignancy requires a dynamic
      interaction between tumour cells and the environment in which they thrive. Over
      the recent years, it has become evident that the (early) inflammatory and
      angiogenic response, and remodelling of the extracellular proteins are key
      factors in creating a microenvironment that sustains tumour growth and
      metastasis. The host response towards cutaneous melanoma has received relatively
      little attention, most likely because the majority of these tumours develop
      without evoking a strong stromal response as can be observed in, e.g.,
      carcinomas. This review discusses potential critical modulators of melanoma
      growth: turn-over of the most abundant extracellular matrix protein in skin (i.e.
      type I collagen), the early inflammatory response and angiogenesis.

PMID- 15970547
TI  - Inhibition of prostate cancer cellular proteasome activity by a pyrrolidine
      dithiocarbamate-copper complex is associated with suppression of proliferation
      and induction of apoptosis.
AB  - Recent research suggests that copper could be used as a novel selective target
      for cancer therapies. Copper is a co-factor essential for tumor angiogenesis
      processes and high levels of copper have been found in many types of human
      cancers, including prostate, breast and brain. We have reported that organic
      copper-containing compounds, such as 8-hydroxyquinoline-copper(II), are a novel
      class of proteasome inhibitors and tumor cell apoptosis inducers (Daniel et al.,
      Biochem Pharmacol. 2004;67:1139-51). Most recently, we have found that when
      complexed with copper, the known antioxidant pyrrolidine dithiocarbamate (PDTC)
      forms a potent proteasome inhibitor in human breast cancer, but not normal cells
      (Daniel, Chen, et al., submitted). In the current study, we investigate whether
      the PDTC-copper complex can play similar roles in inhibiting the proteasomal
      activity and consequently inducing apoptosis in human prostate cancer cells. We
      used tetrathiomolybdate (TM), a strong copper chelator currently being tested in
      clinical trials, as a control. We report here that after binding to copper, PDTC,
      but not TM, can inhibit the proteasomal chymotrypsin-like activity, suppress
      proliferation, induce apoptotic cell death, and inhibit uptake of
      radiopharmaceutical 2-[18F]Fluoro-2-deoxy-D-glucose in cultured human prostate
      cancer cells. In contrast, PDTC, TM or copper alone or a TM-copper mixture had no
      such effects. Our study suggests that high copper levels in human prostate cancer
      in vivo can be targeted by a ligand such as PDTC, resulting in formation of an
      active proteasome inhibitor and apoptosis inducer specifically in prostate tumor,
      but not normal cells.

PMID- 15970548
TI  - Human osteopetroses and the osteoclast V-H+-ATPase enzyme system.
AB  - Osteopetroses are a heterogeneous group of human genetic diseases characterized
      by generalized increase in bone density due either to a decreased osteoclast
      population, defect in osteoclast function, or both. Current knowledge of the
      pathogenesis suggests defects that may be either intrinsic to osteoclast-monocyte
      lineage or extrinsic to the mesenchymal cells that support osteoblast ontogeny
      and activation. Four clinically distinct forms of human osteopetroses currently
      recognized are the infantile malignant autosomal recessive form, the intermediate
      autosomal recessive form, the adult benign autosomal dominant osteopetrosis type
      I, and the autosomal dominant osteopetrosis type II. Propensity to fracture is
      high in all types of osteopetrosis, and other characteristic clinical problems
      include hematologic and metabolic abnormalities, infections of affected bone, and
      neurologic sequela. Among the infantile malignant clinical forms 50-60% of
      patients present with defects in the OC116-KDa (also refers to ATP6i, TCIRGI, a3)
      subunit of the osteoclast vacuolar H+-ATPase (V-H+-ATPase) proton pump.
      Approaches that have been applied to the treatment of osteopetrosis include those
      aimed at stimulating host osteoclasts. These approaches however have met with
      little success, and it would appear that the future for the successful treatment
      of osteopetrosis lies with bone marrow transplantation. Various animal models
      mimicking some of the clinical subtypes of osteopetrosis have been generated in
      efforts to elicit further understanding of the pathogenesis. This review is an
      update on the various phenotypic presentations of human osteopetroses alongside
      their known animal models. Further studies on these animal models will not only
      expand our basic understanding of the molecular mechanisms of osteopetroses, but
      will also aid our ability to develop therapeutic means of intervention in
      diseases involving osteopetroses.

PMID- 15970549
TI  - Presenilin-1 detection in brain neurons and FOXp3 in peripheral blood mononuclear
      cells: normalizer gene selection for real time reverse transcriptase pcr using
      the DeltaDeltaCt method
AB  - Quantification of gene expression is important to confirm changes in levels of
      gene expression in disease. Prior quantification methods include standard curves,
      absolute quantification, and relative quantification. This paper describes an
      analytic method for the relative quantification of Presenilin-1 (PS-1) in neurons
      and Forkhead-box (FOX) p3 in PBMNCs using real-time PCR analytic techniques. A
      comparative Ct method (deltadelatCt) is described in which the quantity of target
      normalized to a normalizer gene reference is given by 2-deltadelatCt where
      deltadelatCt = [Ct of the gene of interest in the unknown specimen - Ct
      normalizer gene in the unknown specimen] - [Ct of the gene of interest in the
      calibrator specimen - Ct normalizer gene in the calibrator specimen]. The
      calibrator specimen is ideally from a non-treated control specimen and is
      analyzed on every assay plate with the unknown specimens of interest. The use of
      the deltadelatCt methodology allows for a higher throughput and a more economical
      approach to investigate gene expression. We applied this methodology to the
      quantification of PS-1 and FOXp3 genes and compare the levels of expression by
      normalizing to different normalizer genes using the deltadelatCt methodology. We
      find that use of GAPDH is the optimum normalizer gene for the genes analyzed in
      neurons from human brain and in PBMNCs.

PMID- 15970550
TI  - Mechanical strain induces Cbfa1 and type X collagen expression in mandibular
      condyle.
AB  - Core binding factor a1 (Cbfa1) is a crucial transcriptional factor for
      chondrocyte maturation and osteoblast differentiation in the mandibular condyle.
      To quantitatively assess the amount of mRNA expression of Cbfa1 and type X
      collagen in response to mandibular advancement. 420, 35-day-old female Sprague
      Dawley rats, were randomly divided into 20 experimental and 10 control groups
      corresponding to 10 time points. Experimental animals were advanced in either
      single or stepwise manner. Condylar cartilage was dissected under microscope and
      total RNA was extracted, Cbfa1 and type X collagen mRNA was quantified with real
      time RT-PCR. Cbfa1 and type X collagen mRNA expression for all groups reached
      their peak on experimental day 21. During single advancement, Cbfa1 and type X
      collagen mRNA expression was consistently higher (3-fold and 2.8-fold
      respectively) than that of stepwise advancement (2-fold). The second advancement
      in the stepwise group resulted in both Cbfa1 and type X collagen level reaching
      another peak on day 51. Mandibular advancement promoted chondrocytes maturation
      and osteoblast differentiation by upregulating Cbfa1 expression. Stepwise
      advancement produced a higher level of Cbfa1 and type X collagen expression
      leading to bigger cartilage template onto which bone will form through
      endochondral ossification.

PMID- 15970551
TI  - Acquired immunodeficiency syndrome associated lymphoma.
AB  - A prior diagnosis of HIV increases the risk of lymphoma between 150 to 250- fold,
      depending on the subtype, as compared with the risk observed in the general
      population. The advent of highly active anti-retroviral therapy (HAART) has seen
      a dramatic reduction in AIDS morbidity and a modest reduction in the incidence of
      opportunistic infections along with a corresponding reduction in Kaposi's
      sarcoma. There has not, however, been a clear reduction in the incidence of
      lymphoma. As HAART therapy continues to improve in the Western world, the
      morbidity of HIV infection is beginning to shift from AIDS to other associated
      illness such as lymphoma. The treatment and etiology of lymphoma is a burgeoning
      issue in the care of HIV positive populations. This review will provide a basic
      overview of the association between HIV and lymphoma.

PMID- 15970552
TI  - The plasminogen activation system in skeletal muscle regeneration: antagonistic
      roles of urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1).
AB  - The plasminogen activation (PA) system is an extensively used mechanism for the
      generation of proteolytic activity in the extracellular matrix, where it
      contributes to tissue remodeling in a wide range of physiopathological processes.
      Despite the limited information available at present on plasminogen activators,
      their inhibitors and cognate receptors in skeletal muscle, increasing evidence is
      accumulating on their important roles in the homeostasis of muscle fibers and
      their surrounding extracellular matrix. The development of mice deficient for the
      individual components of the PA system has provided an incisive approach to test
      the proposed muscle functions in vivo. Skeletal muscle regeneration induced by
      injury has been analyzed in urokinase-type plasminogen activator (uPA)-, tissue
      type plasminogen activator (tPA)-, plasminogen (Plg)- and plasminogen activator
      inhibitor-1 (PAI-1)-deficient mice and has demonstrated profound effects of these
      molecules on the fibrotic state and the inflammatory response, which contribute
      to muscle repair. In particular, the opposite roles of uPA and its inhibitor PAI
      1 in this process are highlighted. Delineating the mechanisms by which the
      different plasminogen activation system components regulate tissue repair will be
      of potential therapeutic value for severe muscle disorders.

PMID- 15970553
TI  - The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for
      the effective treatment of advanced melanoma.
AB  - Malignant melanoma is a highly aggressive tumor of the pigment-producing cells in
      the skin with a rapidly increasing incidence and a poor prognosis for patients
      with advanced disease that is resistant to current therapeutic concepts.
      Therefore, the development of novel strategies for treating melanoma are of
      utmost importance. In melanoma, both the Ras-Raf-MEK-ERK (MAPK) and the PI3K-AKT
      (AKT) signaling pathways are constitutively activated through multiple
      mechanisms, and thus exert several key functions in melanoma development and
      progression. Conversely, several molecules known to play key roles in melanoma
      development and progression such as the adhesion molecules E-/N-cadherin, MelCAM
      and alphavbeta3 integrin are regulated by these pathways and/or activate the
      same. The results of the research to date indicate that in melanoma both the MAPK
      and the AKT signaling pathways may represent promising therapeutic targets.

PMID- 15970554
TI  - DNA hypomethylation of individual sequences in aborted cloned bovine fetuses.
AB  - Cloned bovines have a much higher abortion rate than those derived in vivo.
      Available evidence indicates that inappropriate epigenetic reprogramming of donor
      nuclei is the primary cause of cloning failure. To gain a better understanding of
      the DNA methylation changes associated with the high abortion rate of cloned
      bovines, we examined the DNA methylation status of a repeated sequence (satellite
      I) and the promoter regions of two single-copy genes (interleukin 3/cytokeratin)
      in aborted cloned fetuses, aborted fetuses derived from artificial insemination
      (AI), cloned adults and AI adults by bisulfite sequencing and restriction enzyme
      analysis. Two of four aborted cloned fetuses show very low methylation levels in
      the two single-copy gene promoter regions. One of the two fetuses also showed
      undermethylated status in the satellite I sequence. The other two aborted cloned
      fetuses have similar methylation levels to those of aborted AI fetuses. However,
      no difference in methylation was observed between cloned adults and AI adults.
      Our results demonstrate for the first time the undermethylated status of
      individual sequences in aborted cloned fetuses. These findings suggest that
      aberrant DNA methylation may contribute to the developmental failure of cloned
      bovine fetuses.

PMID- 15970555
TI  - Technical note: preliminary results in development of a novel intracisternal
      penicillin seizure model in the rat.
AB  - In order to develop an intracisternal penicillin rat model of epilepsy, eleven
      anesthetized male Wistar rats were studied. 5 underwent intracisternal injection
      of penicillin (doses 150,000-300,000 units) in the prone position, and another 5
      underwent intraperitoneal penicillin injection; one died following intracisternal
      injection, prior to further study. Time between penicillin injection and seizure
      induction (determined by electroencephalography) was recorded. Each animal had a
      tracheostomy, and was mechanically ventilated and carefully monitored for adverse
      effects. Seizures were noted in an average of 13:42 minutes following penicillin
      injection (range 4:30-23:20) for the intracisternally (IC) injected group. Both
      episodic and continuous seizure activity was seen, and a dose-dependent effect
      was seen (quicker-onset, more continuous seizures with higher doses, in the IC
      group). Onset was significantly faster in the IC than for the intraperitoneally
      injected group (all >1 hour for the latter group in our study). 96 total separate
      seizure episodes were seen, ranging from 3 to 540 seconds. Epileptic activity
      could be seen in all IC-injected rats lasting over 1 hour into the study. The
      intracisternal penicillin injection rat model appears to provide a quick-onset,
      reliable method of inducing seizure activity in the rat model while leaving the
      cranial vault intact.

PMID- 15970556
TI  - Electroconvulsive therapy for seizure control: preliminary data in a new seizure
      generation and control model.
AB  - Electroconvulsive therapy (ECT) effect upon seizure cessation was studied in five
      male Wistar rats using a penicillin intracisternal injection model (which did not
      damage the cranial vault). Animals were observed both clinically and
      electrographically for seizure development. ECT was applied at varying times
      following onset of seizure, at varying parameters (frequency, pulsewidth, and
      duration). ECT affected EEG seizure pattern in several different stimulation
      parameter-dependent ways: (1) modulation to different pattern; (2) increased
      interictal time; and (3) seizure cessation. Stimulation with higher, sustained
      current (50 mA) led to changes in seizure amplitude; stimulation at pulses of
      current led to seizure frequency dimunition, and at certain characteristic pulses
      "capture" was seen as the EEG activity mimicked the ECT-inducing stimulation
      pattern. Interictal time was usually increased by sustained, continuous (rather
      than pulsatile) stimulation. Seizure activity was completely stopped in several
      instances using parameters of 800 pulses at a frequency of 200 Hz, with 2.56 ms
      pulsewidth and 50 mA of current (in consecutive iterations for one specimen). No
      ECT-related adverse effects were noted. Analogous to the heart, pacing or
      defibrillating the brain using external scalp electrodes may have a role in the
      control of otherwise intractable seizures.

PMID- 15970557
TI  - The spectrin-associated cytoskeleton in mammalian heart.
AB  - The membrane-associated cytoskeleton of the cardiac muscle cell is emerging as an
      important element in the maintenance of normal cell functioning. Recently it was
      shown that when proteins (betaII-spectrin, muscle Lim-only protein, ankyrin-B,
      ankyrin-G) of this system are defective or deficient, cardiac malfunction ensues.
      It is well-established that the spectrin cytoskeleton is associated with the
      plasma membrane, but it was only lately demonstrated that its components also lie
      on internal cell membranes. This is particularly apparent in muscle cells of the
      heart which contain specialised intracellular membrane compartments particular to
      this cell type such as the sarcoplasmic reticulum and T-tubules. Cardiomyocytes
      are subjected to constant mechanical stress. Since their mechanics are controlled
      through coordination of calcium fluxes mediated via cell membrane-based
      assemblies, it is imperative that these essential elements withstand the
      displacement forces of contraction. Cardiomyocyte spectrin locates the
      multifunctional spectrin/actin-binding and membrane-binding component, protein
      4.1, and they act together on the plasma membrane as well as on internal
      membranes. We have found that cardiac protein 4.1 links to the calcium handling
      apparatus whilst spectrins connect with the sarcomeric contractile elements of
      the cell. Overall this assembly fulfils roles in stabilising cardiomyocyte cell
      membranes and in coordinating the macromolecular protein accumulations which
      regulate and accomplish cardiac molecular crosstalk, whilst at the same time
      enabling the muscle cells to resist extreme forces of contraction.

PMID- 15970558
TI  - Neuro-immunity in stress-related oral ulcerations: a fractal analysis.
AB  - By testing archival paraffinized biopsy blocks obtained from the oral pathology
      library with immunohistochemistry, we tested the hypothesis that substantial
      alterations are demonstrable in the cross-talk between sympathetic (VMAT) and
      para-sympathetic innervation (VAchT), and resident CD3+ T cells in the mucosa
      from oral lichen planus (OLP), compared to recurrent aphthous stomatitis (RAS)
      and control biopsies. We quantified fractal dimension and Euclidean dimension of
      CD3+ cells between the two pathologies, and across the set of CD3+ cells proximal
      to the vesicles of monoamines transport (VMAT)+ or the vesicles of acetylcholine
      transport (VAchT)+ innervation, compared to cells relatively distal to the nerve
      endings. The data show exquisite organization of the punctuate sympathetic and
      para-sympathetic staining about the resident CD3+ T cells in the OLP lesions, but
      not in the aphthous lesions or in control mucosa. Fractal analysis reveals that
      aphthous lesions are characterized by CD3+ T cells of larger size (Euclidean
      dimensional map), compared to control mucosa. CD3+ T cells in OLP lesions are
      also found to be significantly larger than those found in control lesions, when
      they are not proximal to sympathetic or para-sympathetic vesicles. The membrane
      of CD3+ T cells is overall more complex (fractal dimension) in aphthous lesions,
      compared to control sections. A similar trend is apparent, albeit not
      statistically significant, in CD3+ T cells resident in OLP lesions, whether or
      not they are located proximal to nerve endings. An overall decrease in the ratio
      of fractal dimension-over-topological dimension was also observed across the
      pathological lesions, compared to control. Taken together, these data indicate
      that as CD3+ T cells grow larger in the pathological conditions, they, in effect,
      stretch their plasma membrane, and that the cells may be at different stage of
      the cell cycle, relative to their position vis a' vis nerve endings. Because
      fractal analysis is performed on individual cells, it has the potential of being
      developed in a novel diagnostic test, as well as a prognostic tool for monitoring
      the etiology and the course of treatment at the individual cellular level. Our
      findings also open new frontiers of fundamental, clinical and translational
      biosciences of OLP.

PMID- 15970559
TI  - Colorectal liver metastasis: towards the integration of conventional and
      molecularly targeted therapeutic approaches.
AB  - Radical surgery currently represents the only treatment with curative potential
      for patients with colorectal cancer (CRC) liver metastases. Unfortunately, only a
      minority of cases is eligible for hepatic resection and many patients still
      develop recurrent disease, which underscores the need for more effective adjuvant
      treatments. In case of unresectable disease, locoregional therapeutic strategies
      can obtain significant tumor regression/local disease control rates, but there is
      no definitive evidence of their effect on patients' survival. In regards to
      systemic chemotherapy, the conduction of randomized controlled trials has led to
      a substantial progress in terms of both tumor response and survival rates.
      Despite these results, most patients ultimately die of their disease due to
      hepatic and/or extra-hepatic cancer progression. Therefore, novel therapeutic
      strategies are urgently needed to improve the prognosis of patients with
      metastatic CRC. The elucidation of CRC biology is paving the way to the
      development of molecularly targeted strategies, and results from controlled
      clinical trials have already demonstrated that some agents targeting tumor
      specific molecules can significantly improve the therapeutic efficacy of
      conventional antineoplastic drugs. The dissection of the molecular mechanisms of
      CRC metastatization and tumor/host interactions will not only accelerate the
      development of more effective and less toxic anticancer strategies but also will
      allow for the personalization of the therapeutic regimen according to the
      molecular features of individual patients and their tumors. Only the broader
      clinical implementation of these novel molecular oncology findings and the
      optimal integration of conventional and molecularly targeted therapeutic
      approaches will enable clinicians to provide patients with a better chance of
      cure.

PMID- 15970560
TI  - Temperature- and pH-sensitive core-shell nanoparticles self-assembled from poly(n
      isopropylacrylamide-co-acrylic acid-co-cholesteryl acrylate) for intracellular
      delivery of anticancer drugs.
AB  - Temperature- and pH-sensitive amphiphilic polymer poly(N-isopropylacrylamide-co
      acrylic acid-co-cholesteryl acrylate) (P(NIPAAm-co-AA-co-CHA)) has been
      synthesized and employed to encapsulate paclitaxel, a highly hydrophobic
      anticancer drug, in core-shell nanoparticles fabricated by a membrane dialysis
      method. The nanoparticles are spherical in shape, and their size can be made
      below 200 nm by varying fabrication parameters. The lower critical solution
      temperature (LCST) of the nanoparticles is pH-dependent. Under the normal
      physiological condition (pH 7.4), the LCST is well above the normal body
      temperature (37 degrees C) but it is below 37 degrees C in an acidic environment
      (e.g. inside the endosome or lysosome). The critical association concentration of
      the polymer is determined to be 7 mg/L. Paclitaxel can be easily encapsulated
      into the nanoparticles. Its encapsulation efficiency is affected by fabrication
      temperature, initial drug loading and polymer concentration. In vitro release of
      paclitaxel from the nanoparticles is responsive to external pH changes, which is
      faster in a lower pH environment. Cytotoxicity of paclitaxel-loaded nanoparticles
      against MDA-MB-435S human breast carcinoma cells is slightly higher than that of
      free paclitaxel. In addition, doxorubicin is used as a probe to study cellular
      uptake using a confocal laser scanning microscope (CLSM). Doxorubicin molecules
      are able to enter the cytoplasm after escaping from the endosome and/or the
      lysosome. The temperature- and pH-sensitive nanoparticles would make a promising
      carrier for intracellular delivery of anticancer drugs.

PMID- 15970561
TI  - Finding dominant sets in microarray data.
AB  - Clustering allows us to extract groups of genes that are tightly coexpressed from
      Microarray data. In this paper, a new method DSF_Clust is developed to find
      dominant sets (clusters). We have preformed DSF_Clust on several gene expression
      datasets and given the evaluation with some criteria. The results showed that
      this approach could cluster dominant sets of good quality compared to kmeans
      method. DSF_Clust deals with three issues that have bedeviled clustering, some
      dominant sets being statistically determined in a significance level, predefining
      cluster structure being not required, and the quality of a dominant set being
      ensured. We have also applied this approach to analyze published data of yeast
      cell cycle gene expression and found some biologically meaningful gene groups to
      be dug out. Furthermore, DSF_Clust is a potentially good tool to search for
      putative regulatory signals.

PMID- 15970562
TI  - Transglutaminase and diseases of the central nervous system.
AB  - Alzheimer's disease, Parkinson's disease and diseases of expanded polyglutamine
      are associated with insoluble protein aggregates and neuronal death. A role for
      transglutaminase in the stabilization of these aggregates has been proposed.
      Diseases of polyglutamine expansion have been the most thoroughly investigated
      and a large body of studies supports the causative role of transglutaminase in
      aggregation of expanded polyglutamine. However none of the evidence is
      conclusive. Indisputable evidence of cross-linking by transglutaminase will be
      required in order to provide firm support for therapeutic measures based on the
      role of transglutaminase.

PMID- 15970563
TI  - Apoptosis in alcoholic and nonalcoholic steatohepatitis.
AB  - Alcohol liver disease (ALD) as well as nonalcoholic fatty liver disease (NAFLD)
      are two of the most common forms of chronic liver disease worldwide and may
      progress to cirrhosis and end stage liver disease. ALD and NAFLD seem to share
      many pathophysiologic mechanisms with the accumulation of lipids in the liver
      being the first step in the development of both conditions. While mitochondrial
      dysfunction and production of reactive oxygen species seem to play an important
      role in the progression from simple steatosis to steatohepatitis in both
      diseases, the pathogenesis of ALD and NAFLD as it relates to tissue injury
      remains poorly understood. Insights into these mechanisms are of significant
      clinical importance because current therapies for both conditions are limited and
      future therapies will be predicated by an understanding of their pathogenesis. In
      this review we focused on the current evidence for a central role of
      hepatocellular apoptosis, a specific form of cell death, in the pathogenesis of
      ALD and NAFLD as well as the current knowledge regarding the subcellular and
      molecular mechanisms involve in triggering hepatocyte apoptosis in these
      diseases.

PMID- 15970564
TI  - The Na/K-ATPase-mediated signal transduction as a target for new drug
      development.
AB  - The Na/K-ATPase, or Na+ pump, is a member of the P-type ATPase superfamily. In
      addition to pumping ions, the Na/K-ATPase is a receptor that not only regulates
      the function of protein kinases, but also acts as a scaffold, capable of
      tethering different proteins into a signalplex. The signaling Na/K-ATPase resides
      in caveolae and forms a "binary receptor" with the tyrosine kinase Src.
      Endogenous cardiotonic steroids and digitalis drugs such as ouabain act as
      agonists and provoke this binary receptor, resulting in tyrosine phosphorylation
      of the proteins that are either associated with, or in close proximity to, the
      signaling Na/K-ATPase. Subsequently, this initiates protein kinase cascades
      including ERKs and PKC isozymes. It also increases mitochondrial production of
      reactive oxygen species (ROS) and regulates intracellular calcium concentration.
      Like other receptors, activation of the Na/K-ATPase/Src by ouabain induces the
      endocytosis of the plasma membrane Na/K-ATPase. Significantly, this newly
      appreciated signaling function of the Na/K-ATPase appears to play an important
      role in the pathogenesis of many cardiovascular diseases, therefore serving as an
      important target for development of novel therapeutic agents.

PMID- 15970565
TI  - Expression of HSP105 and HSP60 during germ cell apoptosis in the heat-treated
      testes of adult cynomolgus monkeys (macaca fascicularis).
AB  - To confirm that transient increase in temperature of the testis (43C for 30
      minutes once daily for 2 consecutive days) could induce apoptosis of germ cells
      in non-human primates and to investigate the possible roles of Hsp105 and Hsp60
      in regulation of germ cell loss, we conducted the study on eight cynomolgus
      monkeys. The sperm concentration on day 28 after heat shock decreased to 8.4% of
      pretreatment levels and recovered to baseline on day 144. Using the TUNEL assay,
      increased numbers of apoptotic spermatocytes and round spermatids were detected
      on days 3, 8, and 30 post heat treatment. Hsp105 and Hsp60 mRNA and protein
      levels were analyzed using in situ hybridization, RT-PCR, immunohistochemical and
      Western blot methods. Hsp105 was confined to nuclei of spermatids before
      treatment, decreased dramatically with the loss of spermatids on days 3, 8, and
      30, before returning to baseline levels on days 84 and 144. The expression of
      Hsp60 was high on days 3, 8, 30 and was only detected in Sertoli cells and
      spermatogonia. These results suggested that exposure of the testis to heat
      resulted in selective, but reversible damage to the seminiferous epithelium via
      increased germ cell apoptosis. Temporal changes in the expression pattern of
      Hsp105 and Hsp60 in relation to germ cell death suggests they may be involved in
      key processes in regulation of germ cell apoptosis.

PMID- 15970566
TI  - Gastric cancer. Treatment of advanced disease and new drugs.
AB  - Gastric cancer is most chemosensitive among gastrointestinal tumors. However, the
      role of chemotherapy in advanced disease and its advantage over best supportive
      care has been adequately addressed only in the last decade. First generation
      regimens, such as 5-Fluorouracil (5-FU), Doxorubicin, Mitomycin C (FAM) have been
      used until early 90's, when evidence from randomized studies came up in favour of
      second generation regimens, such as 5-FU, Doxorubicin, high-dose Methotrexate
      (FAMTX), which in turn was proven less active than a third generation regimen,
      such as epirubicin, cisplatin, continuous infusion 5-FU (ECF) in a randomized
      study. Newer treatment options came up over last years. The Swiss Group for
      Clinical Cancer Research has carried out a randomized three-arm phase II study
      with ECF or docetaxel, cisplatin (TC), or docetaxel, cisplatin, 5-FU (TCF) in
      advanced gastric cancer. TCF has been selected as the combination to be further
      evaluated in a formal comparison with ECF. Oxaliplatin is being tested in
      advanced gastric cancer. Two recently published phase II studies of biweekly
      infusional 5-FU, folinic acid, and oxaliplatin have shown a considerable
      therapeutic activity. Irinotecan is another drug under investigation in advanced
      gastric cancer, both as single agent and in combination. A randomized phase II
      III study of irinotecan plus cisplatin or irinotecan plus folinic acid/5-FU has
      recently been completed; the latter arm was proven worth undergoing a formal
      comparison with a standard CF regimen. Oral fluoropyrimidines represent a
      suitable therapeutic option in selected groups of patients. Marimastat is a
      matrix metalloproteinase inhibitor, whose main toxicity is musculoskeletal. A
      randomized phase III study of marimastat versus placebo as maintenance therapy in
      advanced gastric cancer has shown a significant survival advantage for the
      marimastat arm, both in the total patient population and in the subgroup of
      patients who had previously received chemotherapy. Since a clear gold standard
      for advanced gastric cancer does not yet exist, the inclusion of patients in well
      designed clinical trials is to be considered the best treatment option.

PMID- 15970567
TI  - Oxidation by reactive oxygen species (ROS) alters the structure of human insulin
      and decreases the insulin-dependent D-glucose-C14 utilization by human adipose
      tissue.
AB  - The formation of dityrosine of human insulin oxidized by metal-catalyzed
      oxidation system (H2O2/Cu) was estimated by fluorescent methods. The oxidation of
      tyrosine and phenylalanine residues present on the insulin molecule was evident
      after 2 minutes of in vitro oxidation due to the formation of protein-bound
      dityrosine. The success of oxidative protein modification was followed until
      available aromatic residues were consumed (60 minutes), measured by their
      emission at 405 nm. The structural and chemical changes on insulin molecule are
      related to the loss of biological activity as assessed by measuring the increase
      of U-14C-glucose utilization by human adipose tissue in a radiorespirometry
      system. The oxidation of glucose (14CO2 production) of the adipose cells was
      increased 35 % (301 +/- 119 to 407 +/- 182 cpm/mg in dry weight. P < 0.05) in
      presence of 0.1 IU and 69 % (301 +/- 119 to 510 +/- 266 cpm/dry weight. P < 0.05)
      for 1.0 IU of insulin. The recombinant human insulin oxidized for 5 minutes only
      increased the glucose oxidation by 25 %. In conclusion, these observations show
      that dityrosine formation and other oxidative chemical changes of insulin due to
      its in vitro oxidation decrease and can abolish its biological activity.

PMID- 15970568
TI  - Regulation of NK cell activation by stimulatory and inhibitory receptors in tumor
      escape from innate immunity.
AB  - Recent years have witnessed our major progresses in understanding the membrane
      bound receptors on NK cells. Although functional studies of ligands for these NK
      cell receptors provide good opportunities to study roles of NK cells in anti
      tumor and anti-virus immunosurveillance, little was known about how these ligands
      expression were modulated under physiological and pathological conditions.
      Several recognition models have been proposed to explain such an issue, which
      include "missing-self", "induced-self" and "modified-self" recognition model.
      Here stimulatory immunoreceptor mediated NK cell activation will be reviewed, and
      possible recognition mechanism by which NK cells operate during interaction with
      target cells will be discussed in details. Tumor escape from NK cell-mediated
      immunosurveillance will also be further addressed.

PMID- 15970569
TI  - Basic helix-loop-helix transcription factors, BHLHB2 and BHLHB3; their gene
      expressions are regulated by multiple extracellular stimuli.
AB  - The E box sequence (5'-CANNTG-3') is found in the transcriptional regulatory
      region of a number of genes. Of the basic helix-loop-helix (bHLH) proteins
      binding to the E box sequence, class B of bHLH proteins, BHLHB2 (also referred to
      as the DEC1/Eip1/SHARP-2/Stra13/Clast5) and BHLHB3 (also referred to as the
      DEC2/SHARP-1/SHARP1), are transcription factors that contain a unique orange
      domain. These transcription factors repress the transcription of target genes not
      only via binding to the E box sequence but also via protein-protein interactions
      with other transcription factors. Both the BHLHB2 and BHLHB3 genes are widely
      expressed in both embryonic and adult tissues. Their gene expressions are
      regulated in a cell type-specific manner by various extracellular stimuli, such
      as growth factors, serum starvation, hypoxia, hormones, nutrient, cytokines,
      light, and infection. Therefore, these transcription factors play pivotal roles
      in multiple signaling pathways that impact many biological processes including
      development, cell differentiation, cell growth, cell death, oncogenesis, immune
      systems, circadian rhythm, and homeostasis. The structural features, functions,
      and biological roles of the novel bHLH transcription factors, BHLHB2 and BHLHB3,
      are discussed along with the mechanisms in which the genes encoding these factors
      are regulated.

PMID- 15970570
TI  - Stem cells for cardiac repair: state of the art.
AB  - Stem cell research has generated great excitement over the last few years. In
      cardiovascular medicine, the possibility to cure heart failure with newly
      generated cardiomyocytes (CMCs) has sparked the interest of many scientists; as a
      result, different "ideal" cardiac stem cells were proposed for therapeutic use.
      We review here the literature in the cardiac stem cell field, which sometimes is
      "dialectic" in methodology and results.

PMID- 15970571
TI  - Expressions and regulation of endothelial and inducible nitric oxide synthases in
      mouse uterus during the estrous cycle and early pregnancy.
AB  - Nitric oxide (NO) has been implicated in many cellular processes. We examined the
      temporal and spatial expressions of endothelial nitric oxide synthase (eNOS) and
      inducible nitric oxide synthase (iNOS) in mouse uteri during the estrous cycle
      and early pregnancy, as well as the regulation of eNOS and iNOS by estradiol (E2)
      and progesterone (P4) in ovariectomized mouse uteri using in situ hybridization
      and immunohistochemistry. Our results showed that positive eNOS and iNOS signals
      were localized in the uterine luminal epithelium and glandular epithelium during
      the estrous cycle. In ovariectomized mice, both E2 and P4 regulated the
      expression of eNOS and iNOS. During early pregnancy, eNOS and iNOS were detected
      not only in epithelium, but also in the primary decidual zone surrounding
      implanting embryos on day 6 of pregnancy, and in the whole decidualized stroma on
      day 7 of pregnancy. In conclusion, the results demonstrated that two NOS isoforms
      were localized in mouse uteri in specific temporal and spatial patterns during
      the estrous cycle and early pregnancy, and ovarian hormones can regulate their
      expression. Furthermore, the data suggest that the expression of NOS during the
      peri-implantation period might lead to enhance NO production, which could promote
      embryo implantation.

PMID- 15970572
TI  - Chronic peritoneal sepsis: myocardial dysfunction, endothelin and signaling
      mechanisms.
AB  - Despite advances in the understanding of pathophysiological mechanisms, there are
      limited pharmacotherapeutic options for sepsis, septic shock, and related
      pathologies. It is surprising that although sepsis-induced myocardial depression
      is documented in clinics, the cellular mechanisms are from clear. Alterations in
      molecular signaling mechanisms activated by cytokines and potent mediators such
      as ET-1 could pose the risk for myocardial dysfunction in sepsis. Our laboratory
      data suggest that the septic heart, in vivo, exhibits an increased time constant
      of left ventricular relaxation, tau, along with changes in LVEDP. We also
      observed that bigET-1-induced elevation of ET-1 correlates with cardiodynamic
      alterations, induction of apoptosis, and activation of p38-MAPK phosphorylation
      during sepsis. In light of these evidences, we emphasize that these molecular
      alterations in heart, both at organ and cellular level during early sepsis, need
      to be elucidated thoroughly.

PMID- 15970573
TI  - Potentially avoidable maternity complications: an indicator of access to prenatal
      and primary care during pregnancy.
AB  - OBJECTIVE: We identified Potentially Avoidable Maternity Complications (PAMCs).
      Used with hospital discharge data, PAMCs may indicate lack of prenatal care
      access. METHODS: A research team of two obstetrician/gynecologists and three
      health services researchers developed the PAMC indicator, which was verified by
      external review. AIM 1 used the National Maternal and Infant Health Survey, with
      prenatal care information and 8,661 pregnancy hospitalizations, to examine
      associations between prenatal care, risk factors, and PAMCs. AIM 2 used the 1997
      Nationwide Inpatient Sample (NIS), with 895,259 pregnancy-related
      hospitalizations, to examine PAMC risks for groups likely to have prenatal care
      access problems. RESULTS: In AIM 1, adequate prenatal care reduced PAMC risks by
      57% (p < .01). Compared to nonsmokers, the odds of a PAMC for smokers were 86%
      higher (p < .01). Cocaine use increased PAMC risk notably (odds ratio 3.35, p <
      .0001). In the multivariate analyses of AIM 2, African Americans, the uninsured,
      and Medicaid beneficiaries had high PAMC risks (all p < .0001). CONCLUSIONS:
      Findings suggest adequate prenatal care may reduce PAMC risks. Results for groups
      with less prenatal care access were consistent with previous research using less
      refined indicators, such as low birth weight. PAMCs improve on earlier measures,
      and readily permit adjustments for mothers' ages and comorbidities.

PMID- 15970574
TI  - UK national Lesbians and Health Care Survey.
AB  - Lesbians are less prevention oriented in their health care behavior than
      heterosexual women and avoid routine screening tests such as Pap smears and
      mammograms. The reasons for these differences have been partly attributed to
      beliefs about risk, (for example, lesbians are said to be at lower risk of
      cervical cancer) and partly attributed to lesbians' poor experiences of health
      care because of heterosexism. The Lesbians and Health Care Survey was conducted
      during the 12 month period of 1997-8. The sample consisted of 1066 lesbians
      living throughout the UK. The study examined whether risk perceptions,
      experiences of health care and health-seeking behavior were correlated. Data were
      analyzed using SPSS to determine which variables were associated with
      participation in screening. While lesbians were less likely than lesbians in a
      similar US study to report that their risk of cervical cancer was the same as
      that of heterosexual women, perceptions of risk were not correlated with
      participation in screening. We assumed that bad experiences of screening would
      act as a barrier to attendance; instead, good experiences were associated with
      the increased likelihood of attendance. These findings under-score the need for a
      pro-active agenda for lesbian health which addresses the need for culturally
      competent health care, the sharing of best practice amongst health care providers
      and the creation of systemic institutional change to improve the care lesbians
      receive.

PMID- 15970575
TI  - Correlates of self-efficacy for physical activity in African American women.
AB  - This study examined the correlates of self-efficacy for physical activity in
      African American women. In bivariate analyses, self-efficacy was higher among
      women reporting fewer social role constraints, more positive perceptions of
      physically active women, more positive sense of community, better perceived
      health, and higher levels of physical activity. In a simultaneous multivariate
      model, more positive perceived health status (p = .001), higher physical activity
      level (p = .007), and lower social role constraint (p = .02) were independently
      associated with higher self-efficacy. Thus, physical activity interventions for
      African-American women should include strategies to decrease social role
      constraint and offer safe activities for women with health conditions hindering
      physical activity.

PMID- 15970576
TI  - Social network normative influence and sexual risk-taking among women seeking a
      new partner.
AB  - This paper examines the relative influence of social network norms on sexual risk
      taking among women seeking a new partner in Quebec (Canada). A survey was
      conducted among 430 women, 30 to 54 years of age, and living without a partner.
      Condom use is significantly influenced by the norms of women's different social
      networks: confidants, social circles through which they meet partners (e.g.,
      family, friends, internet or newspapers virtual communities), with a minority
      following prescribed condom use habits. Further the results indicate that among
      the study participants the search for love and well being, social proximity,
      feelings of trust and intimacy that appear to evolve almost instantly in new
      encounters, are in conflict with the prescribed condom-use norms. These results
      suggest that there is a need to build new norms for starting relationships, for
      improved dialogue among women and between women and men on affective solitude.
      The findings also underscore the need for public health interventions that seek
      to influence social networks as well as the behavior of individuals.

PMID- 15970577
TI  - News media coverage of a women's health contraversy: how newspapers and TV
      outlets covered a recent debate over screening mammography.
AB  - Over the past decade, there have been several highly visible debates about
      mammography that have captured professional, public and media attention. This
      paper looks at newspaper and television news coverage of a controversial research
      letter in The Lancet by Gotzsche and Olsen (2001) that concluded that screening
      mammography did not prevent deaths from breast cancer. The news pieces examined
      for this project were published between October 2001 and March 2002 in one of
      eight U.S. newspapers or aired on one of six national or cable news networks. The
      six-month period was divided into one-week segments; the numbers of articles
      published or stories aired in each week were graphed to examine patterns. Each
      newspaper article and television transcript was then reviewed to identify its
      main content area and the amount of coverage for each major event was quantified.
      The highest number of newspaper articles appeared to result from several events
      during the end of January through the beginning of February. These events
      included the publication of another meta-analysis of mammography that disputed
      the original letter's conclusion and a full-page New York Times advertisement
      paid for by major medical organizations stating their continued support for
      mammography. The greatest amount of television news coverage was devoted to the
      announcement of the official federal guidelines by the Secretary of Health and
      Human Services in late February. We conclude by discussing how the flow of news
      coverage of medical controversies can potentially impact the actions and
      reactions of the public, the medical community and health policy makers.

PMID- 15970578
TI  - Postpartum health in mothers of term and preterm infants.
AB  - Mothers have inadequate information about what to expect in the postpartum period
      in terms of their own health. Understanding common patterns of postpartum health
      may be particularly important for mothers of preterm low birthweight infants, so
      that they can plan how to optimize their own health as they care for their
      vulnerable infants. The purpose of this study was to compare the health of
      mothers of preterm and term infants prospectively for the first four months
      following delivery. This longitudinal descriptive study measured health status of
      33 mothers of preterm infants and 32 mothers of term infants using health diaries
      and the Health Review Questionnaire every month for the first four months
      following delivery. No difference was observed between the two groups of mothers
      in how ill mothers reported feeling over time. The most common symptoms mothers
      experienced were headaches and cold symptoms. On average mothers reported between
      one and four days every month that they were not able to conduct their usual
      activities. Mothers reported feeling ill more frequently than they sought health
      care. The average mother at four months postpartum was still reporting she felt
      ill between 3 and 7 days during the month. This study has implications for
      families, health care providers, and policy makers.

PMID- 15970579
TI  - Perinatal mental health in lesbian mothers: a review of potential risk and
      protective factors.
AB  - Postpartum depression and other perinatal mental illnesses are common
      complications of childbirth. The majority of research on these conditions has
      been conducted in heterosexual women; however, increasing numbers of women are
      choosing to parent in the context of lesbian relationships. Although many of the
      fundamental aspects of the transition to parenthood are shared between lesbian
      and heterosexual mothers, lesbian mothers may differ from heterosexual parents on
      a number of variables that have been previously associated with perinatal mental
      health. Lesbian mothers may be more likely than their heterosexual peers to lack
      social support, particularly from their families of origin, and may be exposed to
      additional stress due to homophobic discrimination. However, the likelihood that
      lesbian pregnancies will be planned, together with the relatively equal division
      of child-care labour observed in lesbian couples, may offer protection from
      perinatal depression. The study of perinatal mental health in lesbian mothers is
      warranted, both to ensure that the mental health needs of this largely invisible
      population are being met, and to further illuminate the role of psychosocial
      stress in perinatal mental health in all women.

PMID- 15970580
TI  - Whole body positron emission tomography/computed tomography (PET/CT) tumour
      staging with integrated PET/CT colonography: technical feasibility and first
      experiences in patients with colorectal cancer.
AB  - AIM: The aim of this study was to implement an imaging protocol for positron
      emission tomography/computed tomography (PET/CT) colonography and to combine this
      protocol with whole body PET/CT tumour staging for a single whole body
      examination for routine clinical use. SUBJECTS AND METHODS: A whole body PET/CT
      protocol for tumour staging and a protocol for PET/CT colonography were
      integrated into one examination. Fourteen prospective patients with suspected
      colorectal cancer underwent whole body PET/CT after aqueous bowel distension and
      pharmacological bowel relaxation. Colonoscopy and histopathology served as the
      standards of reference in all patients. RESULTS: The modified PET/CT examination
      detected all but one lesion in the colon. One additional lesion was detected in a
      patient with incomplete colonoscopy due to high grade luminal stenosis. One polyp
      with malignant conversion was identified with the modified PET/CT protocol.
      PET/CT colonography proved accurate in local lymph node staging and staged nine
      out of 11 patients correctly. Six additional extracolonic tumour sites were
      detected based on the whole body staging approach. CONCLUSION: Whole body PET/CT
      with integrated colonography is technically feasible for whole body staging in
      patients with colorectal cancer. Based on these initial diagnostic experiences,
      this integrated protocol may be of substantial benefit in staging patients with
      colorectal cancer, focusing on patients with incomplete colonoscopy and those
      with small synchronous bowel lesions.

PMID- 15970581
TI  - An approach to studying lung cancer-related proteins in human blood.
AB  - Early stage lung cancer detection is the first step toward successful clinical
      therapy and increased patient survival. Clinicians monitor cancer progression by
      profiling tumor cell proteins in the blood plasma of afflicted patients. Blood
      plasma, however, is a difficult cancer protein assessment medium because it is
      rich in albumins and heterogeneous protein species. We report herein a method to
      detect the proteins released into the circulatory system by tumor cells.
      Initially we analyzed the protein components in the conditioned medium (CM) of
      lung cancer primary cell or organ cultures and in the adjacent normal bronchus
      using one-dimensional PAGE and nano-ESI-MS/MS. We identified 299 proteins
      involved in key cellular process such as cell growth, organogenesis, and signal
      transduction. We selected 13 interesting proteins from this list and analyzed
      them in 628 blood plasma samples using ELISA. We detected 11 of these 13 proteins
      in the plasma of lung cancer patients and non-patient controls. Our results
      showed that plasma matrix metalloproteinase 1 levels were elevated significantly
      in late stage lung cancer patients and that the plasma levels of 14-3-3 sigma,
      beta, and eta in the lung cancer patients were significantly lower than those in
      the control subjects. To our knowledge, this is the first time that fascin,
      ezrin, CD98, annexin A4, 14-3-3 sigma, 14-3-3 beta, and 14-3-3 eta proteins have
      been detected in human plasma by ELISA. The preliminary results showed that a
      combination of CD98, fascin, polymeric immunoglobulin receptor/secretory
      component and 14-3-3 eta had a higher sensitivity and specificity than any single
      marker. In conclusion, we report a method to detect proteins released into blood
      by lung cancer. This pilot approach may lead to the identification of novel
      protein markers in blood and provide a new method of identifying tumor biomarker
      profiles for guiding both early detection and therapy of human cancer.

PMID- 15970582
TI  - Quantitative neuropeptidomics of microwave-irradiated mouse brain and pituitary.
AB  - In neuropeptidomics, the degradation of a small fraction of abundant proteins
      overwhelms the low signals from neuropeptides, and many neuropeptides cannot be
      detected by mass spectrometry without extensive purification. Protein degradation
      was prevented when mice were sacrificed with focused microwave irradiation,
      permitting the detection of hypothalamic neuropeptides by mass spectrometry. Here
      we report an alternative and very simple method utilizing an ordinary microwave
      oven to inhibit enzymatic degradation. We used this technique to identify brain
      and pituitary neuropeptides. Quantitative analysis using mass spectrometry in
      combination with stable isotopic labeling was performed to determine the effect
      of microwave irradiation on relative levels of neuropeptides and protein
      degradation fragments. Microwave irradiation greatly reduced the levels of
      degradation fragments of proteins. In contrast, neuropeptide levels were
      increased about 2-3 times in hypothalamus by the microwave irradiation but not
      increased in pituitary. In a second experiment, three brain regions
      (hypothalamus, hippocampus, and striatum) from microwave-irradiated mice were
      analyzed. Altogether 41 neuropeptides or fragments of secretory pathway proteins
      were identified after microwave treatment; some of these are novel. These
      peptides were derived from 15 proteins: proopiomelanocortin, proSAAS,
      proenkephalin, preprotachykinins A and B, provasopressin, prooxytocin, melanin
      concentrating hormone, proneurotensin, chromogranins A and B, secretogranin II,
      prohormone convertases 1 and 2, and peptidyl amidating monooxygenase. Although
      some protein degradation fragments were still found after microwave irradiation,
      these appear to result from protein breakdown during the extraction and not to an
      enzymatic reaction during the postmortem period. Two of the protein fragments
      corresponded to novel protein forms: VAP-33 with a 7-residue N-terminal extension
      and beta tubulin with a glutathione on the Cys near the N terminus. In
      conclusion, microwave irradiation with an ordinary microwave oven effectively
      inhibits enzymatic postmortem protein degradation, increases the recovery of
      neuropeptides, and makes it possible to conduct neuropeptidomic studies with
      mouse brain tissues.

PMID- 15970583
TI  - Analysis of intimal proteoglycans in atherosclerosis-prone and atherosclerosis
      resistant human arteries by mass spectrometry.
AB  - The propensity to develop atherosclerosis varies markedly among different sites
      in the human vasculature. To determine a possible cause for such differences in
      atherosclerosis susceptibility, a proteomics-based approach was used to assess
      the extracellular proteoglycan core protein composition of intimal hyperplasia
      from both the atherosclerosis-prone internal carotid artery and the
      atherosclerosis-resistant internal thoracic artery. The intimal proteoglycan
      composition in these preatherosclerotic lesions was found to be more complex than
      previously appreciated with up to eight distinct core proteins present, including
      the large extracellular proteoglycans versican and aggrecan, the basement
      membrane proteoglycan perlecan, the class I small leucine-rich proteoglycans
      biglycan and decorin, and the class II small leucine-rich proteoglycans lumican,
      fibromodulin, and prolargin/PRELP (proline arginine-rich end leucine-rich repeat
      protein). Although most of these proteoglycans seem to be present in similar
      amounts at the two locations, there was a selective enhanced deposition of
      lumican in the intima of the atherosclerosis-prone internal carotid artery
      compared with the intima of the atherosclerosis-resistant internal thoracic
      artery. The enhanced deposition of lumican in the intima of an atherosclerosis
      prone artery has important implications for the pathogenesis of atherosclerosis.

PMID- 15970584
TI  - MALDI-TOF mass spectrometry analysis of cerebrospinal fluid tryptic peptide
      profiles to diagnose leptomeningeal metastases in patients with breast cancer.
AB  - Leptomeningeal metastasis (LM) is a devastating complication that occurs in 5% of
      patients with breast cancer. Early diagnosis and initiation of treatment are
      essential to prevent neurological deterioration. However, early diagnosis of LM
      remains challenging because 25% of cerebrospinal fluid (CSF) samples produce
      false-negative results at first cytological examination. We developed a new, MS
      based method to investigate the protein expression patterns present in the CSF
      from patients with breast cancer with and without LM. CSF samples from 106
      patients with active breast cancer (54 with LM and 52 without LM) and 45 control
      subjects were digested with trypsin. The resulting peptides were measured by
      MALDI-TOF MS. Then, the mass spectra were analyzed and compared between patient
      groups using newly developed bioinformatics tools. A total of 895 possible peak
      positions was detected, and 164 of these peaks discriminated between the patient
      groups (Kruskal-Wallis, p<0.01). The discriminatory masses were clustered, and a
      classifier was built to distinguish patients with breast cancer with and without
      LM. After bootstrap validation, the classifier had a maximum accuracy of 77% with
      a sensitivity of 79% and a specificity of 76%. Direct MALDI-TOF analysis of
      tryptic digests of CSF gives reproducible peptide profiles that can assist in
      diagnosing LM in patients with breast cancer. The same method can be used to
      develop diagnostic assays for other neurological disorders.

PMID- 15970585
TI  - Structural elucidation of chalcone reductase and implications for deoxychalcone
      biosynthesis.
AB  - 4,2',4',6'-Tetrahydroxychalcone (chalcone) and 4,2',4'-trihydroxychalcone
      (deoxychalcone) serve as precursors of ecologically important flavonoids and
      isoflavonoids. Deoxychalcone formation depends on chalcone synthase and chalcone
      reductase; however, the identity of the chalcone reductase substrate out of the
      possible substrates formed during the multistep reaction catalyzed by chalcone
      synthase remains experimentally elusive. We report here the three-dimensional
      structure of alfalfa chalcone reductase bound to the NADP+ cofactor and propose
      the identity and binding mode of its substrate, namely the non-aromatized
      coumaryl-trione intermediate of the chalcone synthase-catalyzed cyclization of
      the fully extended coumaryl-tetraketide thioester intermediate. In the absence of
      a ternary complex, the quality of the refined NADP+-bound chalcone reductase
      structure serves as a template for computer-assisted docking to evaluate the
      likelihood of possible substrates. Interestingly, chalcone reductase adopts the
      three-dimensional structure of the aldo/keto reductase superfamily. The aldo/keto
      reductase fold is structurally distinct from all known ketoreductases of fatty
      acid biosynthesis, which instead belong to the short-chain
      dehydrogenase/reductase superfamily. The results presented here provide
      structural support for convergent functional evolution of these two
      ketoreductases that share similar roles in the biosynthesis of fatty
      acids/polyketides. In addition, the chalcone reductase structure represents the
      first protein structure of a member of the aldo/ketoreductase 4 family.
      Therefore, the chalcone reductase structure serves as a template for the homology
      modeling of other aldo/keto-reductase 4 family members, including the reductase
      involved in morphine biosynthesis, namely codeinone reductase.

PMID- 15970586
TI  - The AUUCU repeats responsible for spinocerebellar ataxia type 10 form unusual RNA
      hairpins.
AB  - Spinocerebellar ataxia type 10 is an autosomal dominant disorder caused by
      expansion of a pentameric repeat tract (ATTCT.AGAAT)(n) in intron 9 of the gene
      that encodes ataxin-10. We have analyzed duplex DNA containing the repeat, the
      individual DNA strands, and the RNA that would be generated by transcription of
      the repeat. Circular dichroism and UV absorbance measurements suggest that the
      previously reported tendency of the repeat to unpair when supercoiled is probably
      related simply to GC content rather than reflecting any unusual property of the
      duplex. DNA containing d(ATTCT)9 forms a folded structure at relatively low
      temperatures, whereas the antisense strand, d(AGAAT)9, does not form a structure
      even at 0 degrees C. In contrast r(AUUCU)9 forms a folded structure under
      physiologically reasonable conditions. S1 nuclease analysis reveals a single
      region of hypersensitivity in the middle of the repeat tract, whereas V1
      digestion is consistent with a hydrogen bonded or well stacked structure. CD
      spectroscopy shows that the structure is unimolecular and hydrogen bonded and has
      a significant amount of A-form helix. NMR spectroscopy demonstrates that these
      hydrogen bonds comprise an equal number of A.U and U.U base pairs. Our data thus
      suggest that the repeat forms an unusual RNA hairpin. Thus the ability to form an
      RNA hairpin seems to be a common property of those Repeat Expansion Diseases that
      are not recessively inherited and are caused by repeats that are transcribed but
      not translated.

PMID- 15970587
TI  - The 3'-azido group is not the primary determinant of 3'-azido-3'-deoxythymidine
      (AZT) responsible for the excision phenotype of AZT-resistant HIV-1.
AB  - The mechanism of human immunodeficiency virus (HIV) 1 resistance to 3'-azido-3'
      deoxythymidine (AZT) involves reverse transcriptase (RT)-catalyzed phosphorolytic
      excision of the chain-terminating AZT-5'-monophosphate (AZTMP). Primers
      terminated with AZTMP are generally better substrates for this reaction than
      those terminated with 2',3'-dideoxynucleoside-5'-monophosphate (2',3'-ddNMP)
      analogs that lack a 3'-azido moiety. This led to the hypothesis that the 3'-azido
      group is a major structural determinant for maintaining the primer terminus in
      the appropriate site for phosphorolytic excision of AZTMP by AZT-resistant
      (AZT(R)) RT. To test this hypothesis, we evaluated the incorporation,
      phosphorolytic excision, and antiviral activity of a panel of 3'-azido-2',3'-ddN
      including 3'-azido-2',3'-ddA (AZddA), 3'-azido-2',3'-ddC (AZddC), 3'-azido-2',3'
      ddG (AZddG), AZT, and 3'-azido-2',3'-ddU (AZddU). The results indicate that
      mutations correlated with resistance to AZT (D67N/K70R/T215F/K219Q) confer
      resistance to the 3'-azidopyrimidine nucleosides (AZddC, AZT, and AZddU) but not
      to the 3'-azidopurine nucleosides (AZddA and AZddG). The data suggest that the
      presence of a 3'-azido group on the 3'-terminal nucleotide of the primer does not
      confer increased phosphorolytic excision by AZT(R) RT for all 3'-azido-ddNMP
      analogs. Thus, the 3'-azido group cannot be the only structural determinant
      important for the enhanced phosphorolytic excision of AZTMP associated with HIV
      resistance to AZT. Other structural components, such as the base, must play a
      role in defining the specificity of the excision phenotype arising from AZT
      resistance mutations.

PMID- 15970588
TI  - A NIMA-related protein kinase is essential for completion of the sexual cycle of
      malaria parasites.
AB  - The molecular mechanisms regulating the sexual development of malaria parasites
      from gametocytes to oocysts in their mosquito vector are still largely
      unexplored. In other eukaryotes, NIMA-related kinases (Neks) regulate cell cycle
      progression and have been implicated in the regulation of meiosis. Here, we
      demonstrate that Nek-4, a new Plasmodium member of the Nek family, is essential
      for completion of the sexual cycle of the parasite. Recombinant Plasmodium
      falciparum Nek-4 possesses protein kinase activity and displays substrate
      preferences similar to those of other Neks. Nek-4 is highly expressed in
      gametocytes, yet disruption of the nek-4 gene in the rodent malaria parasite P.
      berghei has no effect on gamete formation and subsequent fertilization. However,
      further differentiation of zygotes into ookinetes is abolished. Measurements of
      nuclear DNA content indicate that zygotes lacking Nek-4 fail to undergo the
      genome replication to the tetraploid level that precedes meiosis. Cell cycle
      progression in the zygote is identified as a likely precondition for its
      morphological transition to the ookinete and for the successful establishment of
      a malaria infection in the mosquito.

PMID- 15970589
TI  - The homeobox protein MSX2 interacts with tax oncoproteins and represses their
      transactivation activity.
AB  - Bovine leukemia virus (BLV) tax is an essential gene involved in the
      transcriptional activation of viral expression. Tax is also believed to be
      implicated in leukemogenesis because of its ability to immortalize primary cells
      in vitro. To gain insight into the molecular pathways mediating the activities of
      this important gene, we identified cellular proteins interacting with Tax. By
      means of a two-hybrid approach, we show that Tax specifically interacts with
      MSX2, a general repressor of gene expression. GST pull-down experiments and co
      immunoprecipitation assays further confirmed binding specificity. Furthermore,
      the N-terminal residues 1-79 of MSX2 are required for binding, whereas the C
      terminal residues 201-267 of MSX2 do not play a critical role. Whereas the
      oncogenic potential of Tax in primary cells was only slightly affected by
      overexpression of MSX2, the other function of Tax, namely LTR-dependent
      transcriptional activation, was inhibited by MSX2 in human HeLa and bovine B
      lymphoblastoid (BL3) cell lines. This MSX2 repression function can be
      counteracted by overexpression of transcription factors CREB2 and RAP74. The
      Tax/MSX2 interplay thus results in repression of viral transcriptional activation
      possibly acting as a regulatory feedback loop. Importantly, this viral gene
      silencing is not strictly associated with a concomitant loss of Tax oncogenicity
      as measured by its ability to immortalize primary cells. And interestingly, MSX2
      also interacts with and inhibits the transactivation function of the related Tax1
      protein encoded by the Human T-cell leukemia virus type 1 (HTLV-1).

PMID- 15970590
TI  - Accelerated glucose intolerance, nephropathy, and atherosclerosis in
      prostaglandin D2 synthase knock-out mice.
AB  - Type 2 diabetics have an increased risk of developing atherosclerosis, suggesting
      the mechanisms that cause this disease are enhanced by insulin resistance. In
      this study we examined the effects of gene knock-out (KO) of lipocalin-type
      prostaglandin D(2) synthase (L-PGDS), a protein found at elevated levels in type
      2 diabetics, on diet-induced glucose tolerance and atherosclerosis. Our results
      show that L-PGDS KO mice become glucose-in-tolerant and insulin-resistant at an
      accelerated rate when compared with the C57BL/6 control strain. Adipocytes were
      significantly larger in the L-PGDS KO mice compared with controls on the same
      diets. Cell culture data revealed significant differences between insulin
      stimulated mitogen-activated protein kinase phosphatase-2, protein-tyrosine
      phosphatase-1D, and phosphorylated focal adhesion kinase expression levels in L
      PGDS KO vascular smooth muscle cells and controls. In addition, only the L-PGDS
      KO mice developed nephropathy and an aortic thickening reminiscent to the early
      stages of atherosclerosis when fed a "diabetogenic" high fat diet. We conclude
      that L-PGDS plays an important role regulating insulin sensitivity and
      atherosclerosis in type 2 diabetes and may represent a novel model of insulin
      resistance, atherosclerosis, and diabetic nephropathy.

PMID- 15970591
TI  - Structural basis for non-cognate amino acid discrimination by the valyl-tRNA
      synthetase editing domain.
AB  - The editing domain of valyl-tRNA synthetase (ValRS) is known to deacylate, or
      edit, misformed Thr-tRNA(Val) (post-transfer editing). Here, we determined the
      1.7-Angstroms resolution crystal structure of the Thermus thermophilus ValRS
      editing domain. A comparison of the structure with the previously reported tRNA
      complex structure revealed conformational changes of the editing domain upon
      accommodation of the terminal A76; the "GTG loop" moves to expand the pocket, and
      the side chain of Phe-264 on the GTG loop rotates to interact with the A76
      adenine ring. If these conformational changes did not occur, then C75 and A76 of
      the tRNA would clash with Phe-264. To elucidate the mechanism of the threonine
      side-chain recognition, we determined the crystal structure of the editing domain
      bound with [N-(L-threonyl)-sulfamoyl]adenosine at 1.7-Angstroms resolution. The
      gamma-OH of the threonyl moiety is recognized by the Lys-270, Thr-272, and Asp
      279 side chains, which may reject the cognate valyl moiety. Accordingly, ValRS
      mutants with an Ala substitution for Lys-270 or Asp-279 synthesized significant
      amounts of Thr-tRNA(Val). The misproduced Thr-tRNA(Val) was hydrolyzed
      efficiently by the wild-type ValRS, but this post-transfer editing activity was
      drastically impaired by the Ala substitutions for Lys-270 and Asp-279 and was
      also decreased by those for Arg-216, Phe-264, and Thr-272. These results indicate
      that the threonyl moiety and A76 of Thr-tRNA(Val) are recognized by the Lys-270,
      Thr-272, and Asp-279 side chains and by the Phe-264 side chain, respectively, of
      the ValRS editing domain.

PMID- 15970592
TI  - Interaction of calmodulin with the serotonin 5-hydroxytryptamine2A receptor. A
      putative regulator of G protein coupling and receptor phosphorylation by protein
      kinase C.
AB  - The 5-hydroxytryptamine2A (5-HT2A) receptor is a G(q/11)-coupled serotonin
      receptor that activates phospholipase C and increases diacylglycerol formation.
      In this report, we demonstrated that calmodulin (CaM) co-immunoprecipitates with
      the 5-HT2A receptor in NIH-3T3 fibroblasts in an agonist-dependent manner and
      that the receptor contains two putative CaM binding regions. The putative CaM
      binding regions of the 5-HT2A receptor are localized to the second intracellular
      loop and carboxyl terminus. In an in vitro binding assay peptides encompassing
      the putative second intracellular loop (i2) and carboxyl-terminal (ct) CaM
      binding regions bound CaM in a Ca2+-dependent manner. The i2 peptide bound with
      apparent higher affinity and shifted the mobility of CaM in a nondenaturing gel
      shift assay. Fluorescence emission spectral analyses of dansyl-CaM showed
      apparent K(D) values of 65 +/- 30 nM for the i2 peptide and 168 +/- 38 nM for the
      ct peptide. The ct CaM-binding domain overlaps with a putative protein kinase C
      (PKC) site, which was readily phosphorylated by PKC in vitro. CaM binding and
      phosphorylation of the ct peptide were found to be antagonistic, suggesting a
      putative role for CaM in the regulation of 5-HT2A receptor phosphorylation and
      desensitization. Finally, we showed that CaM decreases 5-HT2A receptor-mediated
      [35S]GTPgammaS binding to NIH-3T3 cell membranes, supporting a possible role for
      CaM in regulating receptor-G protein coupling. These data indicate that the
      serotonin 5-HT2A receptor contains two high affinity CaM-binding domains that may
      play important roles in signaling and function.

PMID- 15970593
TI  - TBP-TAF complex SL1 directs RNA polymerase I pre-initiation complex formation and
      stabilizes upstream binding factor at the rDNA promoter.
AB  - Knowledge of the role of components of the RNA polymerase I transcription
      machinery is paramount to understanding regulation of rDNA expression. We
      describe key findings for the roles of essential transcription factor SL1 and
      activator upstream binding factor (UBF). We demonstrate that human SL1 can direct
      accurate Pol I transcription in the absence of UBF and can interact with the rDNA
      promoter independently and stably, consistent with studies of rodent SL1 but
      contrary to previous reports of human SL1. UBF itself does not bind stably to
      rDNA but rapidly associates and dissociates. We show that SL1 significantly
      reduces the rate of dissociation of UBF from the rDNA promoter. Our findings
      challenge the idea that UBF activates transcription through recruitment of SL1 at
      the rDNA promoter and suggest that the rate of pre-initiation complex (PIC)
      formation is primarily determined by the rate of association of SL1, rather than
      UBF, with the promoter. Therefore, we propose that SL1 directs PIC formation,
      functioning in core promoter binding, RNA polymerase I recruitment, and UBF
      stabilization and that SL1-promoter complex formation is a necessary prerequisite
      to the assembly of functional and stable PICs that include the UBF activator in
      mammalian cells.

PMID- 15970594
TI  - Myristic acid stimulates endothelial nitric-oxide synthase in a CD36- and an AMP
      kinase-dependent manner.
AB  - Dietary free fatty acids have been reported to have various effects on the
      endothelium including the generation of nitric oxide. The goal of the current
      study was to determine the mechanism whereby free fatty acid causes an increase
      in nitric oxide synthesis. The specific hypothesis tested was that free fatty
      acid association with CD36, a class B scavenger receptor, induces the activation
      of endothelial nitric-oxide synthase (eNOS). A human microvascular endothelial
      cell line and a transfected Chinese hamster ovary cell system were used to
      determine which free fatty acids stimulate eNOS. Surprisingly, only myristic
      acid, and to a lesser extent palmitic acid, stimulated eNOS. The stimulation of
      eNOS was dose- and time-dependent. Competition experiments with other free fatty
      acids and with a CD36-blocking antibody demonstrated that the effects of myristic
      acid on eNOS required association with CD36. Further mechanistic studies
      demonstrated that the effects of myristic acid on eNOS function were not
      dependent on PI 3-kinase, Akt kinase, or calcium. Pharmacological studies and
      dominant negative constructs were used to demonstrate that myristic acid/CD36
      stimulation of eNOS activity was dependent on the activation of AMP kinase. These
      data demonstrate an unexpected link among myristic acid, CD36, AMP kinase, and
      eNOS activity.

PMID- 15970596
TI  - Conserved structural and functional control of N-methyl-D-aspartate receptor
      gating by transmembrane domain M3.
AB  - The molecular events controlling glutamate receptor ion channel gating are
      complex. The movement of transmembrane domain M3 within N-methyl-d-aspartate
      (NMDA) receptor subunits has been suggested to be one structural determinant
      linking agonist binding to channel gating. Here we report that covalent
      modification of NR1-A652C or the analogous mutation in NR2A, -2B, -2C, or -2D by
      methanethiosulfonate ethylammonium (MT-SEA) occurs only in the presence of
      glutamate and glycine, and that modification potentiates recombinant NMDA
      receptor currents. The modified channels remain open even after removing
      glutamate and glycine from the external solution. The degree of potentiation
      depends on the identity of the NR2 subunit (NR2A < NR2B < NR2C,D) inversely
      correlating with previous measurements of channel open probability. MTSEA-induced
      modification of channels is associated with increased glutamate potency,
      increased mean single-channel open time, and slightly decreased channel
      conductance. Modified channels are insensitive to the competitive antagonists D-2
      amino-5-phosphonovaleric acid (APV) and 7-Cl-kynurenic acid, as well as
      allosteric modulators of gating (extracellular protons and Zn(2+)). However,
      channels remain fully sensitive to Mg(2+) blockade and partially sensitive to
      pore block by (+)MK-801, (-)MK-801, ketamine, memantine, amantadine, and
      dextrorphan. The partial sensitivity to (+)MK-801 may reflect its ability to
      stimulate agonist unbinding from MT-SEA-modified receptors. In summary, these
      data suggest that the SYTANLAAF motif within M3 is a conserved and critical
      determinant of channel gating in all NMDA receptors.

PMID- 15970595
TI  - Vascular endothelial growth factor induction by prostaglandin E2 in human airway
      smooth muscle cells is mediated by E prostanoid EP2/EP4 receptors and SP-1
      transcription factor binding sites.
AB  - Prostaglandin E2 (PGE2) can increase endothelial vascular endogrowth factor A
      (VEGF-A) production but the mechanisms involved are unclear. Here we
      characterized the transcriptional mechanisms involved in human airway smooth
      muscle cells (HASMC). PGE2 increased VEGF-A mRNA and protein but not mRNA
      stability. PGE2 stimulated the activity of a transiently transfected 2068-bp (
      2018 to +50) VEGF-A promoter-driven luciferase construct. Functional 5'
      deletional analysis mapped the PGE2 response element to the 135-bp sequence (
      85/+50) of the human VEGF-A promoter. PGE2-induced luciferase activity was
      reduced in cells transfected with a 135-bp VEGF promoter fragment containing
      mutated Sp-1 binding sites but not in cells transfected with a construct
      containing mutated EGR-1 binding sites. Electrophoretic mobility shift assay and
      chromatin immunoprecipitation assay confirmed binding of Sp-1 to the VEGF
      promoter. PGE2 increased phosphorylation of Sp-1 and luciferase activity of a
      transfected Sp-1 reporter construct. PGE receptor agonists EP2 (ONO-AE1 259) and
      EP4 (ONO-AE1 329) mimicked the effect of PGE2, and reverse transcription-PCR,
      Western blotting, and flow cytometry confirmed the presence of EP2 and EP4
      receptors. VEGF protein release and Sp-1 reporter activity were increased by
      forskolin and isoproterenol, which increase cytosolic cAMP, and the cAMP
      analogue, 8-bromoadenosine-3',5'-cyclophosphoric acid. These studies suggest that
      PGE2 increases VEGF transcriptionally and involves the Sp-1 binding site via a
      cAMP-dependent mechanism involving EP2 and EP4 receptors.

PMID- 15970597
TI  - The tetra-aspartate motif in the activation peptide of human cationic trypsinogen
      is essential for autoactivation control but not for enteropeptidase recognition.
AB  - The activation peptide of vertebrate trypsinogens contains a highly conserved
      tetra-aspartate sequence (Asp(19-22) in humans) preceding the Lys-Ile scissile
      bond. A large body of research has defined the primary role of this acidic motif
      as a specific recognition site for enteropeptidase, the physiological activator
      of trypsinogen. In addition, the acidic stretch was shown to contribute to the
      suppression of autoactivation. In the present study, we determined the relative
      importance of these two activation peptide functions in human cationic
      trypsinogen. Individual Ala replacements of Asp(19-22) had minimal or no effect
      on trypsinogen activation catalyzed by human enteropeptidase. Strikingly, a tetra
      Ala(19-22) trypsinogen mutant devoid of acidic residues in the activation peptide
      was still a highly specific substrate for human, but not for bovine,
      enteropeptidase. In contrast, an intact Asp(19-22) motif was critical for
      autoactivation control. Thus, single Ala mutations of Asp(19), Asp(20) and
      Asp(21) resulted in 2-3-fold increased autoactivation, whereas the Asp(22) -->
      Ala mutant autoactivated at a 66-fold increased rate. These effects were
      multiplicative in the tri-Ala(19-21) and tetra-Ala(19-22) mutants. Structural
      modeling revealed that the conserved hydrophobic S2 subsite of trypsin and the
      unique Asp(218), which forms part of the S3-S4 subsite, participate in distinct
      inhibitory interactions with the activation peptide. Finally, mutagenesis studies
      confirmed the significance of the negative charge of Asp(218) in autoactivation
      control. The results demonstrate that in human cationic trypsinogen the Asp(19
      22) motif per se is not required for enteropeptidase recognition, whereas it is
      essential for maximal suppression of autoactivation. The evolutionary selection
      of Asp(218), which is absent in the large majority of vertebrate trypsins,
      provides an additional mechanism of autoactivation control in the human pancreas.

PMID- 15970598
TI  - The modification of the conserved GXXXG motif of the membrane-spanning segment of
      subunit g destabilizes the supramolecular species of yeast ATP synthase.
AB  - The supernumerary subunit g is found in all mitochondrial ATP synthases. Most of
      the conserved amino acid residues are present in the membrane C-terminal part of
      the protein that contains a dimerization motif GXXXG. In yeast, alteration of
      this motif leads to the loss of subunit g and of supramolecular structures of the
      ATP synthase with concomitant appearance of anomalous mitochondrial morphologies.
      Disulfide bond formation involving an engineered cysteine in position 109 of
      subunit g and the endogenous cysteine 28 of subunit e promoted g + g, e + g, and
      e + e adducts, thus revealing the proximity in the mitochondrial membrane of
      several subunits e and g. Disulfide bond formation between two subunits g in
      mitochondria increased the stability of an oligomeric structure of the ATP
      synthase in digitonin extracts. These data suggest the participation of the
      dimerization motif of subunit g in the formation of supramolecular structures and
      is in favor of the existence of ATP synthase associations, in the inner
      mitochondrial membrane, whose masses are higher than those of ATP synthase
      dimers.

PMID- 15970599
TI  - The PsbH protein is associated with the inner antenna CP47 and facilitates D1
      processing and incorporation into PSII in the cyanobacterium Synechocystis PCC
      6803.
AB  - Analysis of a number of PSII complexes detectable in the wild-type and mutant
      cells of the cyanobacterium Synechocystis sp. PCC 6803 showed that the PsbH
      protein is present in the complexes containing CP47, including unassembled CP47.
      In a mutant lacking CP47, in which the PSII assembly is stopped at the level of
      the D1-D2-cytochrome b-559 reaction centre complex, a negligible amount of the
      PsbH protein was not bound to this complex but was detected in the free form. The
      results indicate that the PsbH protein has a high affinity for CP47 and during
      PSII assembly most probably first associates with CP47 and this pair is
      subsequently attached to the reaction centre complex. Similarly to CP47, the PsbH
      protein exhibits a slow light-induced degradation in the presence of protein
      synthesis inhibitor. The absence of the PsbH protein leads to a greatly increased
      D1 pool that is not associated with other PSII proteins or it is present as a
      part of the reaction centre complex. We conclude that PsbH is important for the
      prompt incorporation of the newly synthesized D1 protein into PSII complexes and
      for the fast D1 maturation.

PMID- 15970600
TI  - A sex pheromone, protoplast release-inducing protein (PR-IP) inducer, induces
      sexual cell division and production of PR-IP in Closterium.
AB  - The sex pheromone protoplast release-inducing protein (PR-IP) inducer and a
      sexual cell division-inducing pheromone-minus (SCD-IP-minus) that mediates the
      sexual reproduction of the heterothallic Closterium peracerosum-strigosum
      littorale (C. psl) complex were investigated in this study. Recombinant PR-IP
      inducer produced by yeast cells was prepared and assayed for production of PR-IP
      and induction of SCD. Both biological activities were observed after treating
      mating-type plus (mt+) cells with the recombinant pheromone. SCD was induced by
      exposure to a lower concentration of the same pheromone and by a shorter
      treatment period with the pheromone than was production of PR-IP. This indicates
      that the previously characterized PR-IP inducer has both PR-IP-inducing and SCD
      inducing activities with mt+ cells, although the inducing mechanisms of the two
      pheromones differ.

PMID- 15970601
TI  - Defining residential tobacco home policies: a behavioural and cultural
      perspective.

PMID- 15970602
TI  - Gases from fossil fuel combustion: a danger to infants?

PMID- 15970603
TI  - Time to review the value of imaging after urinary tract infection in infants.

PMID- 15970604
TI  - The National Service Framework for Children.

PMID- 15970605
TI  - Conjugate vaccines.

PMID- 15970606
TI  - Parent reported home smoking bans and toddler (18-30 month) smoke exposure: a
      cross-sectional survey.
AB  - AIMS: To study the relation between the use of parent reported home smoking bans
      and smoke exposure among children aged 18-30 months. METHODS: A total of 309
      smoking households with children aged 18-30 months, who were part of the Coventry
      Cohort study, consented to participate in this cross-sectional survey. RESULTS:
      Although parents in almost 88% of smoking households reported using harm
      reduction strategies to protect their toddlers from smoke exposure, only 13.9%
      reported smoking bans in the house. Mean log urinary cotinine:creatinine ratio
      was significantly lower for those children whose parents reported no smoking in
      the house (1.11, 95% CI 0.64 to 1.49) compared with none/less strict strategies
      (1.87, 95% CI 1.64 to 2.10). In linear regression models fitted on log
      cotinine:creatinine ratio, no smoking in the house was independently associated
      with a significant reduction in cotinine:creatinine ratio (B = -0.55, 95% CI 
      0.89 to -0.20) after adjusting for mother's and partner's average daily cigarette
      consumption, housing tenure, and overcrowding. The final model accounted for
      44.3% of the variance. CONCLUSIONS: Not smoking in the house was associated with
      a reduction in mean urinary cotinine:creatinine ratio in children aged 18-30
      months; the relation persisted after adjustment for levels of mother's and
      partner's daily cigarette consumption and sociodemographic factors. Results
      suggest that home smoking bans in this age group have a small but significant
      effect on smoke exposure independent of levels of parental tobacco consumption.

PMID- 15970607
TI  - Silver nitrate burns following umbilical granuloma treatment.

PMID- 15970608
TI  - The prevalence and clinical characteristics of cystic fibrosis in South Asian
      Canadian immigrants.
AB  - BACKGROUND: Cystic fibrosis (CF) is considered to be rare among individuals from
      the Indian subcontinent. Furthermore, affected individuals are reported to
      experience a more severe clinical course. AIMS: It was hypothesised that CF is
      under diagnosed in people of South Asian origin and therefore the prevalence may
      be higher than previously estimated. METHODS: The prevalence of CF in the South
      Asian and in the general population living in the same geographic region
      (Metropolitan Toronto) were compared between 1996 and 2001. Population data were
      obtained from the Canadian census survey. CF phenotype and genotype data were
      obtained from the Toronto CF database. RESULTS: Among 381 patients with CF, 15
      were of South Asian descent. The age related prevalence of CF among the South
      Asian and general populations was: 0-14 years, 1:9200 versus 1:6600; 15-24 years,
      1:13,200 versus 1:7600; older than 25 years, 1:56,600 versus 1:12,400. Age at
      diagnosis, duration and severity of symptoms at diagnosis, current nutritional
      status, and FEV(1) were similar in the two groups. While not significant, FEV1
      tended to be lower (48% versus 57% predicted) among adult South Asians, compared
      to the general CF population. Also, the percentage with pancreatic sufficiency
      was higher (27% versus 16%) and the frequency of DeltaF508 allele was lower (50%
      versus 65.1%). CONCLUSIONS: These data suggest that the prevalence and natural
      history of CF in South Asians is similar to that among individuals of European
      origin. The relatively lower prevalence among older South Asians may reflect an
      improving recognition of CF in this ethnic subgroup.

PMID- 15970609
TI  - Changing patterns of childhood mortality in Wolverhampton.
AB  - OBJECTIVES: To review the incidence and characteristics of preventable childhood
      deaths in an urban population in the UK and to determine whether the excess of
      preventable deaths seen previously in Asian girls still exists. DESIGN: A
      retrospective survey of childhood deaths from 1996-2002 classified in terms of
      preventability and compared with a previous study conducted 20 years earlier from
      1976-82. SETTING: The city of Wolverhampton in the UK. MAIN OUTCOME MEASURES:
      Deaths from all causes in children under the age of 5 years. RESULTS: There has
      been a reduction in the number of deaths in all age groups and from all causes.
      The postneonatal mortality rate fell from 6.5/1000 in 1976 to 3.1/1000 live
      births in 2002 largely because of the fall in the numbers of deaths caused by
      sudden infant death syndrome (SIDS). Preventable deaths are still associated with
      low birth weight (p<0.001) and poverty (unemployment and overcrowding in the
      earlier study (p<0.05) and with the Townsend score in this study (p<0.02)). There
      were fewer deaths among Asians and no female excess. There was a new category not
      seen in the previous study, deaths caused by homicide. The death rate for
      homicide in the first year of life was much higher in Wolverhampton
      (18.7/100,000) than in England and Wales (4.6/100,000). CONCLUSIONS: Low birth
      weight and adverse socioeconomic conditions remain important factors associated
      with preventable deaths. There is no longer an increased risk of preventable
      death in Asian girls. The number of non-accidental deaths is a major cause for
      concern.

PMID- 15970610
TI  - How to avoid paediatric medication errors: a user's guide to the literature.
AB  - The National Health Service, in its report An organisation with memory, has
      called for a fundamental rethinking of the way the healthcare system learns from
      error. The NHS further details its goal to reduce serious medication errors by
      40% in a second report entitled Building a safer NHS: improving medication
      safety. This report calls for a review of paediatric medication delivery systems
      to assess safety for children.

PMID- 15970611
TI  - Dental disease in children with chronic illness.
AB  - This article aims to raise awareness among paediatricians and specialist
      paediatric services that poor oral health, in particular children with chronic
      illness, is a major cause of morbidity and can be a risk factor for severe, even
      life threatening complications. Good oral health and dentition is important for
      efficient mastication, speaking and of course, cosmetically for smiling. If left
      untreated, dental caries can lead to pain and infection. Chronic infection around
      one or more teeth can result in damage to localised structures, such as the
      developing permanent teeth. Children who are medically compromised (such as being
      immunocompromised from disease and/or therapy) however are at increased risk of
      developing systemic complications from dental infections, which may prove fatal.
      We focus on the role of the general paediatrician in promoting the importance of
      good dental health for all children and in particular those children "at risk".
      We present preventive measures, evidence based where available, that may improve
      dental care and promote the role of paediatric dental services in the
      multidisciplinary management of chronic disease.

PMID- 15970612
TI  - Respiratory management of the infant with type 1 spinal muscular atrophy.
AB  - A recent paper has highlighted the differences in the respiratory management
      offered to infants with type 1 spinal muscular atrophy (SMA-1). Current views
      appear polarised between those who would offer nothing, to those who would
      proceed as far even as tracheostomy and long term invasive ventilation for these
      infants. Here we offer a personal view, as a possible template for managing a
      vexed and emotional problem. The complex non-respiratory aspects of the holistic
      care of these infants will not be discussed.

PMID- 15970613
TI  - Infantile cortical hyperostosis.

PMID- 15970614
TI  - From hemp seed and porcupine quill to HRCT: advances in the diagnosis and
      epidemiology of bronchiectasis.
AB  - Over the last decade there has been a significant improvement in our ability to
      recognise non-cystic fibrosis (CF) bronchiectasis in children. The precise
      incidence is uncertain, and it varies greatly depending on the populations
      studied and the methods used to make the diagnosis. It is unlikely that many of
      the underlying causes of non-CF bronchiectasis will be eradicated in the near
      future, and so it must be expected that with ever improving technology this
      diagnosis will be made with increasing frequency. This emphasises the need to
      improve our understanding of the aetiology, pathophysiology, epidemiology, and
      management options for children with this group of conditions.

PMID- 15970615
TI  - Children of Jehovah's Witnesses and adolescent Jehovah's Witnesses: what are
      their rights?
AB  - The Jehovah's Witnesses Society (JW), a fundamentalist Christian sect, is best
      known to laypersons and healthcare professionals for its refusal of blood
      products, even when such a refusal may result in death. Since the introduction of
      the blood ban in 1945, 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.

PMID- 15970616
TI  - MRSA at an English children's hospital from 1998 to 2003.
AB  - AIMS: To investigate the epidemiological and clinical aspects of MRSA among
      inpatients and outpatients presenting to hospital. METHODS: Analysis of
      demographic, epidemiological, and clinical data collected on 385 children first
      identified as having MRSA between January 1998 and December 2003 in a 250 bed
      English children's hospital. RESULTS: There were 267 inpatients and 118
      outpatients. The number of new cases of MRSA declined from 72 in 1998 to 52 in
      2003, whereas hospital activity increased. Ninety nine (37.1%) inpatients
      acquired MRSA outside the hospital; a further 90 occurred among 31 clusters of
      cases. One hundred and seventy eight (66.7%) inpatients were aged <2 years;
      cardiac services and paediatric & neonatal surgery accounted for 59.6% of cases.
      Dermatology and A&E accounted for 51.7% of outpatients; 73.8% of outpatients had
      recently previously attended the hospital. A total of 13.9% of inpatients with
      MRSA developed bacteraemia; MRSA accounted for 15% of Staphylococcus aureus
      bacteraemias. The risk of MRSA bacteraemia in colonised patients, and the
      proportion of S aureus bacteraemias that were MRSA, varied between specialties.
      Intravascular devices were the most common source of MRSA bacteraemia (63.4% of
      cases). The mortality rate was 7.3%. CONCLUSIONS: Enhanced surveillance of MRSA
      can identify at-risk patient groups, thus facilitating targeting of control
      measures. The absence of a link between numbers of cases of acquisition of MRSA
      and bacteraemia suggests that the rise in MRSA bacteraemia may not solely reflect
      an increase in MRSA prevalence in children in the UK. The need for larger
      epidemiological studies is emphasised.

PMID- 15970617
TI  - A new formula for blood transfusion volume in the critically ill.
AB  - BACKGROUND: Published formulae, frequently used to predict the volume of
      transfused red cells required to achieve a desired rise in haemoglobin (Hb) or
      haematocrit (Hct), do not appear to have been validated in clinical practice.
      AIMS: To examine the relation between transfusion volume and the resulting rise
      in Hb and Hct in critically ill children. METHODS: Phase 1: Sample of 50% of
      children admitted during 1997; 237 of these 495 patients received at least one
      packed red cell transfusion; 82 children were transfused without confounding
      factors that could influence the Hb/Hct response to transfusion and were analysed
      further. Actual rise in Hb concentration or haematocrit was compared to that
      expected from use of existing formulae. A new formula was developed. Phase 2: In
      50 children receiving a packed red cell transfusion during 2001, actual rise in
      Hb concentration was compared to expected rise in Hb with use of the new formula.
      RESULTS: Phase 1: Existing formulae performed poorly; median ratio of
      actual/predicted rise in Hb or Hct ranged from 0.61 to 0.85. Using the regression
      coefficients new formulae were developed for both Hb and Hct. These formulae were
      applicable across all age and diagnostic groups. Phase 2: Median ratio of
      actual/predicted rise in Hb improved to 0.95 with use of the new formula.
      CONCLUSIONS: Existing formulae underestimate the volume of packed red cells
      required to achieve a target Hb or Hct. Adoption of the new formulae could reduce
      the number of transfusion episodes in PICU, cutting costs and reducing risk.

PMID- 15970618
TI  - The presence of vesicoureteric reflux does not identify a population at risk for
      renal scarring following a first urinary tract infection.
AB  - BACKGROUND: Childhood urinary tract infection (UTI) with or without
      vesicoureteric reflux (VUR) may predispose to renal scarring. There is no clear
      consensus in the literature regarding imaging following UTI in infancy. AIMS: To
      define the role of cystography following a first UTI in children aged under 1
      year, when urinary tract ultrasonography (US) is normal. METHODS: Retrospective
      data collection of 108 children (216 renal units) aged under 1 year at the time
      of a bacteriologically proven UTI. All had a normal US and underwent both
      catheter cystogram and DMSA test. Sensitivity, specificity, likelihood ratios
      positive and negative, and diagnostic odds ratio were calculated for VUR on
      cystography versus scarring on DMSA. RESULTS: VUR was shown in 25 (11.6%) renal
      units. Scarring on DMSA was seen in 8 (3.7 %) kidneys. Only 16% of kidneys with
      VUR had associated scarring; 50% of scarred kidneys were not associated with VUR.
      The likelihood ratio positive was 4.95 (95% CI 2.22 to 11.05) and the likelihood
      ratio negative was 0.56 (95% CI 0.28 to 1.11). The diagnostic odds ratio was 8.9,
      suggesting that cystography provided little additional information. CONCLUSION:
      Since only 16% of children with VUR had an abnormal kidney, the presence of VUR
      does not identify a susceptible population with an abnormal kidney on DMSA. In
      the context of a normal ultrasound examination, cystography contributes little to
      the management of children under the age of 1 year with a UTI. In this context, a
      normal DMSA study reinforces the redundancy of cystography.

PMID- 15970619
TI  - A case-control study of SARS versus community acquired pneumonia.
AB  - The clinical, laboratory, and radiological features at presentation of 16
      children (<12 years) with severe acute respiratory syndrome (SARS) and pneumonia
      were compared with 32 age matched patients with community acquired pneumonia for
      determination of predictive factors that could allow early differentiation of the
      two conditions. A definitive contact history was the most important predictor for
      SARS. Raised serum lactate dehydrogenase concentration in the presence of low
      neutrophil count and serum creatine phosphokinase level at presentation also
      indicated an increased likelihood of SARS-coronavirus infection in young
      children.

PMID- 15970620
TI  - Outdoor carbon monoxide, nitrogen dioxide, and sudden infant death syndrome.
AB  - AIMS: To investigate whether infants who died of SIDS were more likely to have
      higher acute and lifetime average exposures to outdoor carbon monoxide (CO) and
      nitrogen dioxide (NO2) than comparison healthy infants. METHODS: A total of 169
      case and 169 matched control infants born between 1988 and 1992, were studied. CO
      and NO2 concentrations, averaged for all days within the infant's lifespan, and
      the last 30 days, 7 days, 3 days, and 1 day of life were obtained from air
      pollutant data provided by the California Air Resources Board. RESULTS: Based on
      monthly aggregated data, average CO and particularly NO2 were associated with
      SIDS count, even after adjustment for seasonal trends. SIDS outcome was not
      significantly associated with high average outdoor CO levels for any time period.
      However, high average outdoor NO2 levels on the last day of the infant's exposure
      period were significantly associated with SIDS; the adjusted odds ratio was 2.34
      (95% CI 1.13 to 4.87). CONCLUSIONS: SIDS may be related to high levels of acute
      outdoor NO2 exposure during the last day of life. Further studies are needed to
      replicate this finding.

PMID- 15970621
TI  - Pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is a rare multisystem disorder characterised by
      progressive calcification and fragmentation of elastic fibres. Recent genetic
      advances have identified the underlying defect to the ABCC6 gene on chromosome
      16p13.1. Patients typically develop cutaneous, ocular, and cardiovascular
      manifestations but there is considerable phenotypic variability. The skin changes
      are usually apparent in adulthood, and rarely observed in childhood. Since the
      prognosis of PXE largely depends on the extent of extracutaneous organ
      involvement early recognition, intervention and lifestyle adjustments are
      important to reduce morbidity. First-degree family members should be carefully
      examined for any cutaneous or ophthalmologic features of PXE.

PMID- 15970622
TI  - Current treatment and prognosis in children with functionally univentricular
      hearts.
AB  - For more than 30 years Fontan-type procedures have been performed for surgical
      treatment in patients with functionally univentricular hearts. Advances in proper
      patient selection, staging of the Fontan palliation, and modifications of the
      surgical technique resulted in continuous improvement of the surgical results
      during the past two decades. However, increasing experience with medium term and
      long term follow-up of the Fontan circulation has drawn attention to a number of
      sequelae and chronic complications affecting a significant number of patients.

PMID- 15970623
TI  - The Programme for Global Paediatric Research.
AB  - Millions of children die every year from malaria, tuberculosis, diarrhoea,
      neonatal disorders, and many other diseases found primarily in low and mid income
      countries. Many devoted clinicians and scientists have contributed significantly
      to the understanding and care of these diseases, however research remains
      disproportionately aimed at diseases affecting those in high income countries.

PMID- 15970624
TI  - Acknowledging contribution to surveillance studies.

PMID- 15970625
TI  - Adeno-associated viral-mediated insulin-like growth factor delivery protects
      motor neurons in vitro.
AB  - Recent work has demonstrated that adeno-associated viral (AAV) vector-mediated
      delivery of the insulin-like growth factor (IGF-I) gene through retrograde axonal
      transport can prolong survival and delay disease onset in the superoxide
      dismutase mutant mouse model of motor neuron (MN) disease. The present experiment
      examines IGF-I gene transfer in vitro. Adenoviral and AAV vectors for IGF-I
      infect neurons triggering expression and secretion of biologically active IGF-I.
      AAV-mediated IGF-I expression in SH-SY5Y neurons protects both cells expressing
      the transgene, and bystanders without transgene expression from glutamate-induced
      apoptosis. Similarly, AAV-mediated IGF-I delivery in primary E15 MN culture
      provides a titer-dependent neuroprotection from glutamate-induced DNA
      fragmentation. Both infected and noninfected neurons are equally protected. These
      observations argue that vector-mediated IGF-I gene transfer induces secretion of
      active IGF-I that acts through direct effects on spinal cord MNs. This mechanism
      may explain the therapeutic effects observed in vivo despite relatively low
      affinity AAV spinal cord uptake.

PMID- 15970626
TI  - Neuroprotective effects of oral administration of triacetyluridine against MPTP
      neurotoxicity.
AB  - Administration of triacetyluridine (TAU) is a means of delivering exogenous
      pyrimidines to the brain, which may help to compensate for bioenergetic defects.
      TAU has previously been shown to be neuroprotective in animal models of
      Huntington's and Alzheimer's diseases. We examined whether oral administration of
      TAU in the diet could exert significant neuroprotective effects against 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity model of Parkinson's
      disease. Administration of TAU significantly attenuated MPTP-induced depletion of
      striatal dopamine and loss of tyrosine-hydroxylase-positive neurons in the
      substantia nigra. These findings suggest that administration of TAU may be a
      novel approach for treating neurodegenerative diseases associated with impaired
      mitochondrial function.

PMID- 15970627
TI  - Dietary supplementation with 3-deaza adenosine, N-acetyl cysteine, and S-adenosyl
      methionine provide neuroprotection against multiple consequences of vitamin
      deficiency and oxidative challenge: relevance to age-related neurodegeneration.
AB  - Folate deprivation induces neurotoxicity that is potentiated by additional
      nutritional and genetic deficiencies including vitamin E and apolipoprotein E
      deficiency. These deficiencies collectively induce oxidative damage, cognitive
      impairment, and compensatory alteration in glutathione generation. Treatment with
      agents that regulate distinct portions of the methionine cycle, including the S
      adenosyl homocysteine hydrolase inhibitor, 3-deaza adenosine, the methyl donor S
      adenosyl methionine, and the antioxidant N-acetyl cysteine, provide
      neuroprotection against various aspects of neurotoxicity in normal and
      apolipoprotein E-deficient mice and in cultured neuronal cells deprived of
      dietary folate and vitamin E and subjected to iron overload. Here it is
      demonstrated that simultaneous treatment with these agents provide superior
      neuroprotection by alleviating individual and overlapping neurotoxic
      consequences. These findings support combinatorial treatments with agents that
      compensate for differential insults in age-related neurodegenerative disorders.

PMID- 15970628
TI  - Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic
      migraine.
AB  - Familial hemiplegic migraine type 2, an autosomal dominant form of migraine with
      aura, has been associated with four distinct mutations in the alpha2-subunit of
      the Na+,K+-ATPase. We have introduced these mutations in the alpha2-subunit of
      the human Na+,K+-ATPase and the corresponding mutations in the Bufo marinus
      alpha1-subunit and studied these mutants by expression in Xenopus oocyte.
      Metabolic labeling studies showed that the mutants were synthesized and
      associated with the beta-subunit, except for the alpha2HW887R mutant, which was
      poorly synthesized, and the alpha1BW890R, which was partially retained in the
      endoplasmic reticulum. [3H]ouabain binding showed the presence of the
      alpha2HR689Q and alpha2HM731T at the membrane, whereas the alpha2HL764P and
      alpha2HW887R could not be detected. Functional studies with the mutants of the B.
      marinus Na+,K+-ATPase showed a reduced or abolished electrogenic activity and a
      low K+ affinity for the alpha1BW890R mutant. Through different mechanisms, all
      these mutations result in a strong decrease of the functional expression of the
      Na+,K+-pump. The decreased activity in alpha2 isoform of the Na+,K+-pump
      expressed in astrocytes seems an essential component of hemiplegic migraine
      pathogenesis and may be responsible for the cortical spreading depression, which
      is one of the first events in migraine attacks.

PMID- 15970629
TI  - Screening for C677T and A1298C MTHFR polymorphisms in patients with epilepsy and
      risk of hyperhomocysteinemia.
AB  - Hyperhomocysteinemia can result from decreased methylenetetrahydrofolate
      reductase (MTHFR) enzyme activity, owing to genetic polymorphisms andor
      inadequate folate intake. This study was aimed at investigating the prevalence of
      C677T and A1298C MTHFR polymorphisms, and their impact on hyperhomocysteinemia in
      95 epileptic patients and 98 controls. Double gradient-denaturing gradient gel
      electrophoresis screening revealed that the frequency of T677 polymorphic allele
      was similar between cases and controls (46.3% vs 42.3%), whereas that of C1298
      allele was significantly higher in patients (30.5% vs 19.4%, p < 0.05).
      Significant differences between the two groups were also found for the
      frequencies of genotypes AA1298 (46.3% in cases vs 67.3% in controls, p < 0.01)
      and AC1298 (46.3% in cases vs 26.6% in controls, p < 0.01). Other genotype
      frequencies did not show any statistically significant differences. Haplotype
      frequencies significantly differed between the two groups. The CT677/AC1298
      diplotype was significantly more frequent in epileptic patients than in controls
      (32.6% vs 18.4%, p < 0.05). Patients treated with enzyme-inducing antiepileptic
      drugs, having this diplotype and concomitant low folate concentration (i.e., <
      3.4 nmol/L), exhibited plasma homocysteine levels significantly higher than
      normal values (27.1 +/- 2.44 micromol/L, p < 0.001). This increase, however, was
      lower than that observed in folate-deficient patients with diplotype TT677/AA1298
      (41.3 +/- 3.41 micromol/L, p < 0.001). Indeed, these two diplotypes could be
      regarded as risk factors for hyperhomocysteinemia. Conversely, we found that the
      CC677/AA1298 diplotype was significantly more frequent in controls (p < 0.01),
      suggesting a protective role. Our study suggests that both C677T and A1298C MTHFR
      polymorphisms should be examined when assessing genetic risk factors of
      hyperhomocysteinemia in epilepsy.

PMID- 15970630
TI  - The mammalian RNA-binding protein Staufen2 links nuclear and cytoplasmic RNA
      processing pathways in neurons.
AB  - Members of the Staufen family of RNA-binding proteins are highly conserved
      cytoplasmic RNA transporters associated with RNA granules. staufen2 is
      specifically expressed in neurons where the delivery of RNA to dendrites is
      thought to have a role in plasticity. We found that Staufen2 interacts with the
      nuclear pore protein p62, with the RNA export protein Tap and with the exon-exon
      junction complex (EJC) proteins Y14-Mago. The interaction of Staufen2 with the
      Y14-Mago heterodimer seems to represent a highly conserved complex as the same
      proteins are involved in the Staufen-mediated localization of oskar mRNA in
      Drosophila oocytes. A pool of Staufen2 is present in neuronal nuclei and
      colocalizes to a large degree with p62 and partly with Tap, Y14, and Mago. We
      suggest a model whereby a set of conserved genes in the oskar mRNA export pathway
      may be recruited to direct a dendritic destination for mRNAs originating as a
      Staufen2 nuclear complex.

PMID- 15970631
TI  - Side effects of combined therapy of methylprednisolone and intravenous
      immunoglobulin in Guillain-Barre syndrome.
AB  - Side effects were compared in 9 patients with Guillain-Barre syndrome treated
      with standard intravenous immunoglobulin (IVIg) only and in 9 treated with
      combined methylprednisolone and IVIg therapy. Headache occurred in 2 in both
      groups, indicative that pre-infusion with steroids does not prevent headache.
      Transient liver function disturbances were present in 2 patients of the former
      group and in 6 of the latter.

PMID- 15970632
TI  - Treatment of end-of-dose wearing-off in parkinson's disease: stalevo
      (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with
      Comtess/Comtan (entacapone) provide equivalent improvements in symptom control
      superior to that of traditional levodopa/DDCI treatment.
AB  - The aim of this study was to evaluate the efficacy of the new optimised levodopa,
      Stalevo (levodopa, carbidopa and entacapone) in patients with Parkinson's disease
      experiencing end-of-dose wearing-off. Treatment with Stalevo was compared to
      treatment with traditional immediate-release levodopa and dopa-decarboxylase
      inhibitor (DDCI) formulations along with adjunct entacapone (Comtess/Comtan). A
      European, open, parallel-group, active treatment-controlled phase IIIb study
      evaluating 176 patients randomised to switch from their current regimen of
      levodopa/DDCI to either an equivalent dose of Stalevo or levodopa/DDCI plus
      entacapone. After 6 weeks, treatments were assessed using the Clinical Global
      Impression of Change, the Unified Parkinson's Disease Rating Scale and a Motor
      Fluctuations Questionnaire. Over 70% of patients in both the Stalevo and adjunct
      entacapone arms felt that they were clinically improved and over 80% experienced
      a reduction in fluctuations. Although there was no significant difference between
      Stalevo and levodopa/DDCI plus entacapone with regard to motor improvement and
      side effects, 81% of patients stated that they preferred treatment with Stalevo
      compared with taking two separate tablets (i.e. levodopa/DDCI and entacapone).
      Stalevo was well tolerated and safe when substituted for levodopa DDCI
      preparations.

PMID- 15970633
TI  - Antigenicity and immunocrossreactivity of orange tree pollen and orange fruit
      allergenic extracts.
AB  - BACKGROUND: It is important to study the crossreactivity between orange tree
      pollen (OTPE) and orange fruit (OFE) due to the high incidence of pollen/food
      related allergies worldwide. The aim of the present study was to determine the
      antigenic relationship between OTPE and OFE. METHODS: OTPE and OFErabbit antisera
      as well as sera from patients allergic to OTPE and OFE were comparatively applied
      in IgG- and/or IgE-specific ELISA inhibition, crossover or inhibition
      immunoblotting assays using OTPE and OFE allergenic extracts as solid phase.
      Periodate and proteinase K treatments were used for carbohydrate and protein
      depletion, respectively. RESULTS: The antigenicity of OTPE and the presence of
      common structures between OTPE and OFE extracts were demonstrated by rabbit IgG
      specific ELISA inhibition and crossover immunoblotting assays. A 30-kDa protein,
      common target of the IgE response on OTPE, OFE and mandarin extract, but absent
      in lemon extract, was identified by ELISA and immunoblot inhibition assays in
      patients suffering from primary sensitization to OTPE in the context of
      occupational exposure. Moreover, biochemical treatments showed that antigenic
      epitopes on the 30-kDa protein contain polypeptidic but no carbohydrate moieties.
      CONCLUSIONS: The antigenicity of OTPE, the presence of common antigenic
      determinants between pollen and citrus fruits and an IgE-specific crossreactive
      protein band of 30 kDa sharing carbohydrate-free epitopes were described. After
      isolation and purification, this common antigen might be useful for allergen
      immunotherapy in pollen/fruit-related allergic patients.

PMID- 15970634
TI  - Lipid transfer proteins from fruit: cloning, expression and quantification.
AB  - BACKGROUND: Lipid transfer proteins (LTP) are stable, potentially life
      threatening allergens in fruits and many other vegetable foods. The aim of this
      study was to clone and express recombinant apple LTP (Mal d 3), as has previously
      been done for peach LTP (Pru p 3) and set up quantitative tests for measuring
      fruit LTPs. METHODS: cDNA for Mal d 3 and Pru p 3 was cloned, expressed in the
      yeast Pichia pastoris and the resulting proteins were purified via cation
      exchange chromatography. The immune reactivity of rMal d 3 was compared to nMal d
      3 by RAST (inhibition), immunoblotting and basophil histamine release testing. To
      obtain monoclonal and monospecific polyclonal antibodies, mice and rabbits were
      immunized with purified nMal d 3. RESULTS: The deduced amino acid sequence of Mal
      d 3 was identical to the published sequence, Pru p 3 differed at two positions
      (S9A and S76H). The rMal d 3 had an IgE-binding potency and biological activity
      close to its natural counterpart. One sandwich ELISA selectively detecting apple
      LTP and another cross-reactive with cherry, nectarine and hazelnut LTP were
      developed. In addition, a competitive RIA was developed with polyclonal rabbit
      antiserum and labeled nMal d 3. CONCLUSION: rMal d 3 (as shown before for rPru p
      3) may be a useful tool for application in component-resolved diagnosis of food
      allergy. Assays for the measurement of LTP will increase the traceability of this
      potentially dangerous allergen.

PMID- 15970635
TI  - Genetic and environmental factors in the immunopathogenesis of atopy: interaction
      of Helicobacter pylori infection and IL4 genetics.
AB  - BACKGROUND: Both genetic and environmental factors, e.g. early childhood
      infections, have a role in the pathogenesis of atopic diseases. OBJECTIVE: To
      examine simultaneously the strength and possible interactions of two known such
      factors, IL4 genetics and Helicobacter pylori infection, on the risk of atopy and
      asthma. METHODS: Gene polymorphism analyses and skin prick tests (SPT) were
      determined in 245 adult asthmatics and 405 nonasthmatic controls of population
      based case-control study. SPTs were used as an indicator of atopy. H. pylori
      infection was verified by detecting anti-H. pylori IgG antibodies in sera.
      RESULTS: A significant negative association was seen between the presence H.
      pylori antibodies and SPT positivity (> or =1 positive reactions) in both
      asthmatics and controls (p = 0.002 and p = 0.025, respectively) but the effect of
      IL-4 polymorphism (SNP -590C/T) was nonsignificant in both groups (p = 0.071 and
      p = 0.072, respectively). However, IL4 genetics had an effect on susceptibility
      to H. pylori: asthmatics carrying the IL4 -590 allele T had a diminished risk to
      be H. pylori infected (OR 0.485 95%CI 0.287-0.819). This effect was not seen in
      controls. Logistic regression analysis indicated that H. pylori and IL4 effects
      on atopy risk are not interdependent. CONCLUSIONS: This study showed that the
      effect of H. pylori infection on atopy risk is stronger than that of IL4
      genetics. There is no interaction between these factors on the pathogenesis of
      atopy suggesting that these factors have distinct immunopathogenetic mechanisms.
      However, the genetic effect may modify the role of infective agents by effecting
      on susceptibility to disease.

PMID- 15970636
TI  - Hazelnut Allergy: evidence that hazelnut can directly elicit specific IgE
      antibody response via activating type 2 cytokines in mice.
AB  - BACKGROUND: Hazelnut is one of the major tree nuts that causes potentially fatal
      food allergy, with underlying mechanisms that are unclear at present. One
      suggestion is that hazelnut allergy results from immune crossreactivity of IgE
      antibodies produced against certain aeroallergens. We tested the hypothesis that
      hazelnut is intrinsically capable of eliciting an allergic response using a mouse
      model. METHODS: Groups of mice were injected intraperitoneally with
      hazelnut/filbert protein extract with or without alum as an adjuvant, and
      hazelnut-specific antibody (IgE, IgG1) responses were examined using optimized
      enzyme-linked immunosorbent assay. Hazelnut-specific type 2 and type 1 cytokine
      responses were evaluated by ex vivo antigen-mediated activation of spleen cells.
      RESULTS: Hazelnut elicited robust IgE and IgG1 antibody responses. Timecourse and
      dose-response analyses further provided evidence for memory type 2-dependent
      antibody responses to hazelnuts. Hazelnut-specific IgE response in two strains of
      mice with different MHC haplotypes and IgE response to hazelnut without the use
      of alum adjuvant asserted that hazelnut is intrinsically an allergenic food. The
      type 2 cytokine analyses revealed that hazelnut sensitization results from
      activation of IL-4 and IL-5, thus providing a mechanistic basis for hazelnut
      specific IgE response. CONCLUSION: Our data argue that hazelnut - a widely
      consumed food - is intrinsically an allergenic food capable of directly eliciting
      hazelnut-binding specific IgE antibodies viaactivation of type 2 cytokines in
      mice.

PMID- 15970637
TI  - Suppression of Th2 immune responses by mekabu fucoidan from Undaria pinnatifida
      sporophylls.
AB  - BACKGROUND: We demonstrated that mekabu fucoidan obtained from Undaria
      pinnatifida (Up) sporophylls augments the type 1 T-helper (Th1) cell response in
      normal BALB/c mice. In this study, we examined the effects of the fucoidan of
      mekabu on the type 2 T-helper (Th2) response in bronchoalveolar lavage fluid
      (BALF) after ovalbumin (OVA) aerosol challenge. METHODS: Mekabu fucoidan (50
      mg/kg) was injected intraperitoneally into BALB/c mice for 4 days, and then the
      mice were sensitized with 50 microg/mouse of OVA plus alum (1 mg/mouse) 1 and 8
      days later. The mice were challenged with OVA delivered using a nebulizer 7, 8
      and 9 days after the second challenge with OVA plus alum. After 24 h, we assessed
      T cell responses in BALF by measuring the amount of Th2 cytokines (IL-4, IL-5, IL
      13) and gamma-interferon (IFN-gamma) produced by Th1 cells. RESULTS: The
      production of Th2 cytokines was suppressed (p < 0.05), and the amount of IFN
      gamma was not increased in the mice treated with mekabu fucoidan. Anti-OVA
      immunoglobulin E (IgE) and IgE levels in serum determined after challenge with
      aerosolized OVA at the end of the experiment were lower (p < 0.05) in the treated
      than in the control mice. CONCLUSIONS: The pulmonary inflammation was relieved by
      mekabu fucoidan, which also downregulated Th2-dominated responses. These results
      indicate that mekabu fucoidan modulates Th2 responses and might be useful for
      treating allergic inflammation.

PMID- 15970638
TI  - BCG immunization at birth and atopic diseases in a homogeneous population of
      Spanish schoolchildren.
AB  - BACKGROUND: The role of immunization with bacillus Calmette-Guerin (BCG) in the
      prevalence of asthma, hay fever and atopic dermatitis is not definitely
      established and seems to be influenced by ethnic background. The aim of this
      study was to analyze the relationship between this immunization and the
      prevalence of those diseases in a homogeneous population of Spanish
      schoolchildren. METHODS: The International Study of Asthma and Allergies in
      Childhood (ISAAC) core and environmental questionnaires were used in four
      different centers of the Spanish North Atlantic coast. Bilbao, San Sebastian and
      Asturias have a universal BCG immunization policy during the first days of life,
      whereas La Coruna discontinued this practice in 1989. Except for this center,
      immunization coverage was above 90%. A random sample of schools of Asturias or
      all schools in the city district (rest of centers) with children 6 and 7 years
      old was surveyed. RESULTS: The participation rate was above 70%. After excluding
      those children born outside Spain, the numbers were 6,762 immunized and 2,828
      nonimmunized. After adjusting for gender, age, smoking habits of the father and
      mother, truck traffic near the household, older and younger siblings and having a
      cat or a dog during the first year of the child's life, the adjusted ORs of the
      BCG-immunized children suffering from asthma, hay fever and atopic dermatitis
      were respectively 0.87 (95% CI 0.76-1.00), 0.87 (0.75-1.01) and 0.89 (0.76-1.05).
      CONCLUSIONS: BCG immunization offers a weak but significant protection against
      asthma and hay fever in Spanish schoolchildren.

PMID- 15970639
TI  - Nasal rinsing with hypertonic solution: an adjunctive treatment for pediatric
      seasonal allergic rhinoconjunctivitis.
AB  - BACKGROUND: Recent but limited evidence suggests that nasal lavage with
      hypertonic saline may be useful as an adjunctive treatment modality in the
      management of pediatric allergic rhinitis. The aim of this study was to clarify
      whether nasal irrigation with hypertonic solution should be routinely recommended
      to children with seasonal grass pollen rhinoconjunctivitis. METHODS: Fourty-four
      children with seasonal grass pollen rhinoconjunctivitis were recruited. Twenty
      two patients were randomized to receive three-times daily nasal rinsing with
      hypertonic saline during the pollen season, which lasted 7 weeks. Twenty-two
      patients were allocated to receive no nasal irrigation and were used as controls.
      Twenty patients per group completed the study. A mean daily rhinoconjunctivitis
      score based on the presence of nasal discharge and obstruction as well as ocular
      symptoms as reddening and itching were calculated for each week of the pollen
      season. Patients were allowed to use oral antihistamines when required and the
      mean number of drugs taken per week was also calculated. RESULTS: The mean weekly
      rhinoconjunctivitis score in the active group was reduced during the whole pollen
      period. This difference was statistically significant in week 6 and 7 of therapy.
      A markedly reduced intake of oral antihistamines was also observed in patients
      allocated to nasal rinsing, being statistically significant in 5 of the 7 weeks.
      No adverse effect was reported in the active group. CONCLUSIONS: This study
      supports the use of nasal rinsing with hypertonic saline in the pediatric patient
      with seasonal allergic rhinoconjunctivitis. This treatment proved to be
      tolerable, inexpensive and effective.

PMID- 15970640
TI  - HLA-DRB1 and anti-cyclic citrullinated peptide antibody production in rheumatoid
      arthritis.
AB  - Anti-cyclic citrullinated peptide antibodies (anti-CCP) are a new diagnostic
      marker for rheumatoid arthritis (RA), which shows a specificity of 97% and a
      sensitivity of 81% in the second generation assay. About 61% of RA patients
      express HLA-DRB1*0401. In a cohort of patients with RA we investigated whether
      the expression of anti-CCP correlates with the carriage of certain genes on the
      HLA-DRB1 locus. Our data reveal a highly significant association between anti-CCP
      and HLA-DR4, and a weaker but still significant association with HLA-DR1. HLA
      DRB1*0401 is not a prerequisite for anti-CCP production, but if HLA-DRB1*0401 was
      present, 90% of our RA patients were anti-CCP positive.

PMID- 15970641
TI  - Much atopy about the skin: genome-wide molecular analysis of atopic eczema.
AB  - BACKGROUND: Atopic eczema (AE) is a chronic inflammatory skin disorder with an
      increasing prevalence in industrialized countries. METHODS: Genox Research
      Incorporation was founded in 1996 to identify new genes involved in allergic
      diseases in collaboration with the National Children's Hospital in Tokyo. In the
      AE project, they have discovered several hundred new genes and partial DNA
      sequences by mainly using microarrays. Here, I review the results obtained using
      transcriptome analysis, performed by Genox and other investigators. RESULTS:
      Transcriptome analysis using skin lesion, CD4+ T cells, monocytes and eosinophils
      derived from AE patients identified some differentially expressed genes which
      became biologically relevant in the following studies. Missing linkages between
      these genes have been found due to the recent development of genomics.
      CONCLUSION: Many AE-related genes found in the genome-wide studies still remain
      to be determined regarding their functions and to be systemically organized.
      After the comprehensive characterization of these genes by further studies, we
      will identify the precise molecular mechanisms involved in AE and other diseases.

PMID- 15970642
TI  - Cell-mediated effector molecules and complicated malaria.
AB  - In this review I attempt to advance hypotheses that might help contribute toward
      understanding the molecular pathogenesis of cerebral malaria (CM) and other
      complications based on a now widely accepted argument that the illness and
      pathology occasioned by Plasmodiumfalciparum infection might not necessarily be
      due to the direct effects of the parasite's 'toxins' and/or exoantigens or even
      its sequestration and consequent attendant effects in vital organs but rather to
      the parasite's mediated production of microbicidal molecules by the host. Tumor
      necrosis factor (TNF)-alpha is implicated in the pathogenesis of complicated
      malaria. There is a positive correlation between high levels of TNF-alpha and
      severity of malaria. The role of nitric oxide in the pathophysiology of
      complicated malaria is not clearly understood. Mononuclear phagocytes by virtue
      of their capacity to secrete toxic intermediates like reactive oxygen
      intermediates can inhibit the growth of both murine and human plasmodia. The role
      of interleukin-10 (IL-10) in malaria is also not well characterized to date. IL
      10 is a powerful immunosuppressor factor. It acts as a natural dampener of
      immunoproliferative and inflammatory responses. Although transforming growth
      factor-beta has a crucial role in inflammation and repair, its role in
      complicated malaria is not too clearly understood. Furthermore, the anatomical
      source of these microbicidal molecules is not precisely known. The role of immune
      complexes (IC) in the pathophysiology of complicated malaria has hitherto not
      been tested. I argue here that IC play a critical role in influencing the outcome
      of malarial disease; IC-mediated stimulation of leukocytes to produce high levels
      of both TNF-alpha and NO and the fact that leukocytes are probably the principal
      anatomical source of these microbicidal and other pro-inflammatory mediators in
      complicated malaria provide a much more plausible explanation for the
      pathogenesis of CM and other complications. I also review the arguments that help
      contribute to rationalize hypoglycemia and hyperlactatemia in malarial disease
      and to some extent severe anemia. I am therefore tempted to conclude that CM and
      other complications are probably immune-mediated diseases or, at least, they
      present an inflammatory pathogenesis.

PMID- 15970643
TI  - Association of low red blood cell folate concentrations with coronary artery
      disease in Iranians: a matched case-control study.
AB  - BACKGROUND: It is not fully established whether the increasing risk of coronary
      artery disease (CAD) is associated with high plasma homocysteine levels or
      components of the homocysteine remethylation pathway, e.g. vitamin B(12) or 5
      methyltetrahydrofolate (5-MTHF) in plasma and red blood cells (RBC). In this
      study, we tested the hypothesis that 5-MTHF in RBC, which represents the long
      term folate status of individuals, may be a more reliable marker of homocysteine
      remethylation pathway disturbances, and its deficiency may be associated with CAD
      in Iranians. METHODS: Plasma total homocysteine (tHcy), vitamin B(12), and plasma
      and RBC 5-MTHF were measured in 200 angiographically documented patients and 200
      controls matched for sex and age. RESULTS: In the plasma, tHcy levels were
      significantly higher in cases compared to controls (geometric mean 12.9 +/- 6.5
      vs. 10.6 +/- 5.6 micromol/l, p = 0.04). However, RBC 5-MTHF (527.2 +/- 185.9 vs.
      461.3 +/- 117.9 nmol/l, p = 0.007) and vitamin B(12) (254.2 +/- 132.8 vs. 182.2
      +/- 110.4 pmol/l, p = 0.04) were significantly higher in controls than patients.
      RBC 5-MTHF was a strong and independent predictor of plasma tHcy (beta = -0.01, p
      = 0.003, r(2) = 0.19). Subjects in the lowest quartile of red-cell 5-MTHF had a
      2.5-fold increased prevalence of CAD compared to subjects in the highest
      quartile. The association of CAD in the first quartile with red-cell 5-MTHF
      remained significant when adjusted for plasma tHcy, vitamin B(12), hypertension
      and hypercholesterolemia (odds ratio, OR 2.3, confidence interval: 1.1-3.9, p =
      0.01). However, the association between CAD in the highest quartile and plasma
      tHcy decreased and became insignificant when adjusted for red-cell 5-MTHF,
      vitamin B(12), hypertension and hypercholesterolemia (OR 1.27, confidence
      interval: 0.96-1.69, p = 0.11). CONCLUSION: In this study, the association
      between CAD and low RBC 5-MTHF was stronger than with plasma 5-MTHF and plasma
      tHcy levels, indicating that RBC 5-MTHF may be a more stable parameter to study
      disturbances in the homocysteine remethylation pathway in Iranians.

PMID- 15970644
TI  - The selective glucocorticoid receptor antagonist ORG 34116 decreases immobility
      time in the forced swim test and affects cAMP-responsive element-binding protein
      phosphorylation in rat brain.
AB  - Glucocorticoid receptor (GR) antagonists can block the retention of the
      immobility response in the forced swimming test. Recently, we showed that forced
      swimming evokes a distinct spatiotemporal pattern of cAMP-responsive element
      binding protein (CREB) phosphorylation in the dentate gyrus (DG) and neocortex.
      In the present study, we found that chronic treatment of rats with the selective
      GR antagonist ORG 34116 decreased the immobility time in the forced swim test,
      increased baseline levels of phosphorylated CREB (P-CREB) in the DG and neocortex
      and affected the forced swimming-induced changes in P-CREB levels in a time- and
      site-specific manner. Overall, we observed that, in control rats, forced swimming
      evoked increases in P-CREB levels in the DG and neocortex, whereas in ORG 34116
      treated animals a major dephosphorylation of P-CREB was observed. These
      observations underscore an important role of GRs in the control of the
      phosphorylation state of CREB which seems to be of significance for the
      immobility response in the forced swim test and extend the molecular mechanism of
      action of GRs in the brain.

PMID- 15970646
TI  - A new experimental rat model of osteosarcoma established by intrafemoral tumor
      cell inoculation, useful for biology and therapy investigations.
AB  - Satisfactory experimental models for preclinical cancer studies must follow
      several criteria: (1) reproducibility of the method used to induce the tumor and
      (2) clinical, pathological and kinetic similarity with the corresponding human
      tumors. We developed a model of osteosarcoma locally induced by the intrafemoral
      injection of osteosarcoma (OSR) cells in Sprague-Dawley rats. This method yields
      nearly 80% of bone tumors at the injection site. These tumors double their volume
      fairly slowly (in approximately 20 days) and lung metastases occur in 96% of the
      animals. The OSR cell-induced tumor is characterized by a direct production of
      mineralized matrix by the tumor cells themselves, as revealed by histochemical
      analysis. The microarchitectural parameters which were quantified by a
      microscanner show an increased trabecular bone volume (+238%) when OSR cells were
      injected in the femur, as compared to controls injected with vehicle.
      Osteoblastic markers such as alkaline phosphatase, osteopontin, osteocalcin and
      bone sialoprotein were expressed by the tumor in vivo, whereas the initially
      injected OSR cells did not express some of these markers, suggesting that OSR
      cells reacquired an osteoblastic phenotype in a favorable environment. The
      clinical, radiological and histological data show that this model shares high
      similarities with the osteocondensing forms of osteosarcoma in humans.

PMID- 15970645
TI  - Conserved epitopes in human and mouse tissue-nonspecific alkaline phosphatase.
      Second report of the ISOBM TD-9 workshop.
AB  - A panel of 19 monoclonal antibodies (MAbs) against human tissue-nonspecific
      (liver/bone/kidney) alkaline phosphatase (TNAP) was obtained through the ISOBM TD
      9 workshop. In the present study, the reactivity of these MAbs has been
      characterized against mouse TNAP. A mouse embryonic stem cell line, frozen
      sections of long bones, alkaline phosphatase extracted from mouse bone, and serum
      were used as the source of TNAP for individual assays. Each MAb was tested for
      immunoreactivity to mouse TNAP by Western blot analysis, immunohistochemistry and
      enzyme immunoassay. Antibodies 314 and 315 reacted strongly with mouse TNAP in
      Western blots, while all other antibodies were negative. By immunohistochemistry,
      antibodies 314, 315 and 333 produced strong positive staining using frozen
      sections, while antibody 334 was moderately positive. Enzyme immunoassays
      indicated that MAb 333 was also able to bind to serum TNAP. These antibodies
      represent very useful reagents to study the pathophysiological expression of TNAP
      in mouse tissues and in mouse serum.

PMID- 15970647
TI  - Specific measurement of o-linked core 2 sugar-containing isoforms of
      hyperglycosylated human chorionic gonadotropin by antibody b152.
AB  - There have been a significant number of reports on the clinical utility of
      measurement of 'hyperglycosylated' isoforms of the pregnancy hormone, human
      chorionic gonadotropin (hCG). Although there are a variety of hCG isoforms which
      can be termed 'hyperglycosylated', the measurements were all made using a unique
      antibody designated B152. This antibody was raised using a choriocarcinoma
      derived form of hCG, which was hyperglycosylated with N- and O-glycans and was
      also 100% 'nicked' hCG. Antibody B152 was recently mapped to a linear epitope
      around a single O-glycan on the beta-subunit of hCG at residue number 132. Thus,
      the antibody can only measure isoforms of hCG that possess a core 2 type of
      branched O-glycan on this portion of the hCG beta-subunit. Isoforms that are
      hyperglycosylated in the hCG alpha-subunit or only on the N-glycans of hCGbeta
      will not be recognized by antibody B152. Apparently, measurements of these core 2
      hCG isoforms have important clinical application in early pregnancy during which
      they are the predominant isoform of hCG until the 6th week of gestation. The
      secretory pattern of these isoforms can be used to predict the health status of
      the pregnancy in fertility clinics. Moreover, the measurements of these core 2
      hCG isoforms are more useful than standard hCG for the prediction of Down
      syndrome pregnancies. The core 2 isoforms are also of important use in cancer
      diagnosis and monitoring since their concentration appears to correlate with
      malignancy.

PMID- 15970648
TI  - Overexpression of the cytochrome p450 activator hpr6 (heme-1 domain protein/human
      progesterone receptor) in tumors.
AB  - OBJECTIVE: Hpr6 (heme-1 domain protein/human progesterone receptor) is one of a
      family of proteins that are implicated in progesterone metabolism, resistance to
      genotoxic agents and steroid biosynthesis. Because these processes are frequently
      misregulated in tumors, we have examined the expression of Hpr6 in a group of
      clinical tumor samples and cancer cell lines. METHODS: Hpr6 expression was
      analyzed by Western blot in extracts from breast, cervix, colon and thyroid cell
      lines and in nonmalignant and adjacent tumor tissue from breast, colon and
      thyroid. Hpr6 localization was determined by immunofluorescence. RESULTS: Hpr6
      expression is significantly elevated in breast tumors in comparison with matched
      nonmalignant tissue and demonstrated limited overexpression in colon and thyroid
      tumors. Hpr6 is strongly expressed in a panel of tumor cell lines originating
      from breast, thyroid and colon. Hpr6 localizes to the perinuclear region of the
      cell, consistent with a role in cell detoxification, signaling and/or sterol
      synthesis. CONCLUSIONS: Hpr6 homologues regulate cytochrome P450 proteins
      implicated in hormone, steroid and xenobiotic chemical metabolism. These are the
      first studies linking Hpr6 expression to cancer progression and cellular
      survival. Our results suggest that Hpr6 is an important marker for cancer
      progression and a potential anticancer therapeutic target.

PMID- 15970649
TI  - Polymorphism in IGF-2 as a surrogate marker for predisposition towards tobacco
      chewing-mediated oral cancer.
AB  - Insulin and insulin-like growth factors (IGFs) are major determinants of
      proliferation and apoptosis, thereby playing a significant role in
      carcinogenesis. Epidemiological evidence associates high levels of INS and IGFs
      with an increased risk of cancer. Polymorphism of the genes involved in insulin
      signaling pathways has been associated with a variable risk for neoplasms in
      different ethnic and environmental backgrounds. In this study, using PCR-RFLP
      based assays, we investigated the distribution of genetic polymorphism in INS and
      IGF-2 genes in tobacco chewing-mediated oral cancer patients (n = 60) and healthy
      controls (n = 45) of Indian ethnic origin. The genotyping was performed for +1127
      INS-Pst1 in INS and +3580 IGF-2-Msp1 in IGF-2. The frequencies of the IGF-2
      genotypes AG, GG and AA found in oral cancer patients were 0.68, 0.2 and 0.12,
      respectively, whereas in noncancer controls these frequencies were 0.27, 0.71 and
      0.02. Frequencies of each allele, i.e. CT, TT and CC of INS gene, were found to
      be nearly equal in the tumor (0.22, 0.75 and 0.03) as well as the normal (0.27,
      0.67 and 0.06) population. A significant difference was observed in genotypic
      frequencies of IGF-2 and INS in the Indian ethnic population as compared to the
      Caucasian, African and Hispanic populations. Polymorphism at +1127 INS-Pst1 locus
      of INS gene does not show an implication in oral cancer, whereas the genotype AG
      or AA at +3580 IGF-2-Msp1 locus of IGF-2 is associated with progression and
      increased risk of oral cancer. From our study we can conclude that single
      nucleotide polymorphisms in the IGF-2 gene can be used as a marker for prediction
      of the risk of oral carcinogenesis.

PMID- 15970650
TI  - Increased expression of myosin light chain kinase mRNA is related to metastasis
      in non-small cell lung cancer.
AB  - BACKGROUND: The invasiveness of tumor cells depends in large part on their
      motility, which in turn depends on cytoskeletal function. A major cytoskeletal
      component involved in cell motility is myosin II, the classical form of myosin
      first identified in muscle but also expressed in nonmuscle cells. Myosin II is
      activated by myosin light chain kinase (MLCK), which phosphorylates it on its
      regulatory light chain. In this context, the contribution made by MLCK to tumor
      cell motility and invasiveness has been investigated extensively in vitro, but
      clinical evidence of such a contribution has been lacking. In the present study,
      therefore, we examined the role of MLCK in the metastasis of non-small cell lung
      cancer (NSCLC) in a clinical setting. METHODS: We measured MLCK mRNA expression
      in tumor samples from 39 NSCLC patients using real-time semiquantitative reverse
      transcription polymerase chain reaction carried out in a LightCycler. We then
      correlated MLCK mRNA expression with known clinicopathological factors. RESULTS:
      We found that levels of MLCK mRNA expression were higher in patients who showed
      disease recurrence and distant metastasis than in those who did not. Moreover,
      the 3-year disease-free survival rate among patients showing lower levels of MLCK
      mRNA expression [log10(MLCK/GAPDH) <1.4] was significantly greater than among
      those showing higher MLCK mRNA expression [log10(MLCK/GAPDH) > or =1.4] (87.5 vs.
      50.0%; log-rank test, p = 0.021). CONCLUSION: These findings are the first
      clinical evidence that expression of MLCK is correlated with disease recurrence
      and distant metastasis in NSCLC.

PMID- 15970652
TI  - Ultrastructural analysis is necessary and sufficient for identification of
      basophils and mast cells.

PMID- 15970651
TI  - Progression analysis of lung squamous cell carcinomas by comparative genomic
      hybridization.
AB  - OBJECTIVE: The genetic mechanisms underlying the development and progression of
      lung squamous cell carcinoma (SCC), the major subtype of non-small cell lung
      cancer, are still unknown. To better understand this disease, we studied the
      association between genetic alterations and the progression of lung SCC. METHODS:
      Chromosomal aberrations in 39 samples of lung SCC, including 21 nonmetastatic and
      18 metastatic carcinomas, were characterized by comparative genomic hybridization
      and statistically correlated to clinical staging and metastatic ability. RESULTS:
      The average gains and losses per patient were significantly higher in the
      advanced-stage lung SCC and metastatic SCC group compared to the early-stage lung
      SCC and nonmetastatic SCC group. Gains of 2p, 20p and losses of 2q, 4q, 5q, 9q,
      13p, 18q correlated with advanced-stage lung SCC. Losses on 2q, 4q, 6p, 16p, 16q,
      18q, 20q, 21q and gains on 2p, 7p, 7q, 20p were more frequent in the metastatic
      SCC group, which was significantly different from the nonmetastatic SCC group.
      Gains on 2p, 20p and losses on 2q, 4q, 18q were not only associated with an
      advanced clinical stage but also with metastases of lung SCC. CONCLUSIONS: The
      results suggest that several chromosomal aberrations (e.g. gains on 2p, 20p and
      losses on 2q, 4q, 18q) may contribute to the progression of lung SCC.

PMID- 15970653
TI  - Cyclooxygenase, a key enzyme family for production of prostaglandins, is present
      in human mast cell lipid bodies.

PMID- 15970654
TI  - Subcellular localization of the cytokines, basic fibroblast growth factor and
      tumor necrosis factor-alpha in mast cells.

PMID- 15970655
TI  - Immunogold ultrastructural techniques identify subcellular sites of chymase,
      Charcot-Leyden crystal protein, and histamine in basophils and mast cells.

PMID- 15970656
TI  - Ultrastructural enzyme-affinity-gold and inhibitor-gold techniques identify
      subcellular sites of histamine and heparin in basophils and mast cells.

PMID- 15970658
TI  - Mast cell-derived mediators of enhanced microvascular permeability, vascular
      permeability factor/vascular endothelial growth factor, histamine, and serotonin,
      cause leakage of macromolecules through a new endothelial cell permeability
      organelle, the vesiculo-vacuolar organelle.

PMID- 15970657
TI  - Piecemeal degranulation of basophils and mast cells is effected by vesicular
      transport of stored secretory granule contents.

PMID- 15970659
TI  - Degranulation and recovery from degranulation of basophils and mast cells.

PMID- 15970660
TI  - Mast cell secretory granules and lipid bodies contain the necessary machinery
      important for the in situ synthesis of proteins.

PMID- 15970662
TI  - The Jak/Stat pathway: a novel way to regulate PI3K activity.
AB  - Phosphoinositide 3-kinases (PI3Ks) have been grouped into three major classes
      that have different substrate specificities. Class IA PI3Ks consist of a
      catalytic and a regulatory subunit and have multiple isoforms that arise from
      different subunit combinations. The role of two of the small regulatory subunits,
      p55alpha and p50alpha, is poorly understood. We have now identified a novel
      function for these subunits and have shown that their expression is specifically
      induced in the involuting mouse mammary gland where they are involved in the
      downregulation of PI3K signalling and Akt/PKB activity. This abrogation of
      survival signalling thru Akt/PKB and its downstream targets is essential for the
      induction of apoptosis. The switch from lactation to involution is associated
      with activation of the transcription factor Stat3, by the cytokine LIF. Stat3 is
      essential for the induction of apoptosis and, in the absence of Stat3 or LIF,
      expression of the p55alpha and p50alpha subunits is abrogated. Surprisingly,
      Stat3 is a direct regulator of p55alpha and p50alpha expression, as demonstrated
      using ChIP assays, and therefore these subunits are not splicing isoforms as
      previously thought. An important implication of our results is that the p55alpha
      and p50alpha small regulatory subunits are regulated independently of the larger
      p85alpha subunit, and have an essential role in Stat3-mediated apoptosis in
      mammary gland.

PMID- 15970663
TI  - H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S.
      cerevisiae.
AB  - The nucleosome, composed of an octamer of highly conserved histone proteins and
      associated DNA, is the fundamental unit of eukaryotic chromatin. How arrays of
      nucleosomes are folded into higher-order structures, and how the dynamics of such
      compaction are regulated, are questions that remain largely unanswered. Our
      recent studies demonstrated that phosphorylation of histone H2B is necessary to
      induce cell death that exhibits phenotypic hallmarks of apoptosis including DNA
      fragmentation and chromatin condensation in yeast (serine 10)1 and in mammalian
      cells (serine 14)2. In this article, we extend these findings by uncovering a
      role for H2B phosphorylation at serine 10 (Ser10) in another biological event
      that is associated with dramatic alterations in higher-order chromatin structure,
      meiosis. Our data show strong staining, indicative of H2B (Ser10)
      phosphorylation, during the pachytene stage of yeast meiotic prophase. These data
      broaden the use of this phosphorylation mark in chromatin remodeling that closely
      correlates with chromatin compaction. How phosphorylation marks are translated
      into meaningful downstream events during processes as diverse as apoptosis and
      meiosis remain a challenge for future studies.

PMID- 15970664
TI  - MRX (Mre11/Rad50/Xrs2) mutants reveal dual intra-S-phase checkpoint systems in
      budding yeast.
AB  - The intra-S-phase checkpoint is a signaling pathway that induces slow DNA
      replication in the presence of DNA damage. In humans, defects in this checkpoint
      pathway might account for phenotypes seen in autosomal recessive diseases
      including ataxia telangiectasia-like disorder and Nijmegen breakage syndrome,
      where MRN complex components,Mre11 and Nbs1, are mutated. Here we provide
      evidence that the equivalent budding yeast complex, MRX (Mre11/Rad50/Xrs2), is
      not required for the intra-S-phase checkpoint in response to DNA alkylation
      damage, but is required in the presence of double-stranded DNA breaks. These data
      indicate, at least in budding yeast, that alternate pathways enforce replication
      slowing depending on the particular DNA lesion.

PMID- 15970666
TI  - Molecular theory of cancer.
AB  - The mutation theory of cancer was always confronted by alternative (vitalistic)
      theories, which insist that cancer (like life itself) cannot be reduced to
      molecular interactions. In fact, the most fundamental feature of the somatic
      mutation theory of cancer is that it is a molecular theory, meaning that all the
      complexity of cancer on any level (e.g., tissue) can be explained on the
      molecular level. To emphasize the essence of mutation theory, cancer-causing
      mutation can be defined as any (a) molecular event that is (b) somatically
      inheritable and (c) selectable (e.g., provides selective advantage in
      restrictive/carcinogenic conditions). Here I review molecular (somatic mutation)
      theory and its alternatives and discuss that molecular interactions can
      completely explain complex tissue phenomena such as benign tumors and stroma
      initiated tumorigenesis. In addition, molecular theory predicts extragenetic
      somatic hereditary in cancer (e.g., posttranslational protein modifications that
      initiate and are supported by positive feedback loops) and also explains the
      relationship between selection for resistance, hallmarks of cancer and genetic
      instability. From molecules to cells to the organism, this review discusses how
      somatically heritable molecular alterations (genetic, epigenetic and
      extragenetic) alter translation of cellular signals, resulting in resistance to
      growth inhibition and apoptosis, that is manifested as secondary hallmarks of
      cancer (metastasis, angiogenesis and immortality) and, finally, as the amazing
      ability of some cancer cells such as canine transmissible sarcoma to 'live in a
      wild' like unicellular mammalian species.

PMID- 15970665
TI  - Structure of Apaf-1 in the auto-inhibited form: a critical role for ADP.
AB  - The pathway of apoptosis is conserved in the three model species: mammals,
      Drosophila, and C. elegans. The apoptotic protease-activating factor 1, an
      essential protein conserved in all three species, is responsible for the
      activation of the initiator caspase-9 in mammalian cells. The structure of the
      auto-inhibited form of Apaf-1 reveals a critical role for ADP, which serves as an
      organizing center for four adjoining domains. The ADP-binding pocket contains
      features that are important for designing other nucleotide analogs. ATP binding
      is a prerequisite for the formation of the apoptosome. Despite strong sequence
      conservation between Apaf-1 and its orthologues in Drosophila and C. elegans, it
      is unclear whether they employ similar mechanisms for their own activation and
      for activating caspases. Much of the underlying mechanisms remain to be
      investigated by structural biology and biochemistry.

PMID- 15970667
TI  - Methylation of MRE11 regulates its nuclear compartmentalization.
AB  - The cellular response to DNA damage includes the orderly recruitment of many
      protein complexes to DNA lesions. The MRE11-RAD50-NBS1 (MRN) complex is well
      known to localize early to sites of DNA damage, but the post-translational
      modifications required to mobilize it to DNA damage sites are poorly understood.
      Recently, we have shown that MRE11 is arginine methylated in a C-terminal glycine
      arginine rich (GAR) domain by protein arginine methyltransferase 1 (PRMT1).
      Arginine methylation is required for the exonuclease activity of MRE11 and the
      intra-S phase DNA damage response. Herein, we report that cells treated with
      methylase inhibitors failed to relocalize MRE11 from PML nuclear bodies to sites
      of DNA damage and formed few gamma-H2AX foci. We also demonstrate that PRMT1 is a
      component of PML nuclear bodies where it colocalizes with MRE11.Using cellular
      fractionation, we demonstrate that methylated MRE11 is predominantly associated
      with nuclear structures and that MRE11 methylated arginines were required for
      this association. These results suggest that MRE11 methylation regulates its
      association with nuclear structures such as PML nuclear bodies and sites of DNA
      damage.

PMID- 15970668
TI  - Chronic imatinib mesylate exposure leads to reduced intracellular drug
      accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport
      pumps.
AB  - Imatinib mesylate is a selective tyrosine kinase inhibitor that is successfully
      used in the treatment of Philadelphia-positive chronic and acute leukaemia's, and
      gastrointestinal stromal tumors. We investigated whether the intended chronic
      oral administration of imatinib might lead to the induction of the intestinal ABC
      transport proteins ABCB1, ABCC1 (MRP1), ABCC2 (MRP2) and ABCG2. Using Caco2 cells
      as an in vitro model for intestinal drug transport, we found that continuous
      exposure (up to 100 days) with imatinib (10 microM) specifically upregulates the
      expression of ABCG2 (maximal approximately 17-fold) and ABCB1 (maximal
      approximately 5-fold). The induction of gene expression appeared to be biphasic
      in time, with a significant increase in ABCG2 and ABCB1 at day 3 and day 25,
      respectively, and was not mediated through activation of the human orphan nuclear
      receptor SXR/NR1I2. Importantly, chronic imatinib exposure of Caco2 cells
      resulted in a approximately 50% decrease in intracellular accumulation of
      imatinib, probably by enhanced ABCG2- and ABCB1-mediated efflux, as a result of
      upregulated expression of these drug pumps. Both ABCG2 and ABCB1 are normally
      expressed in the gastrointestinal tract and it might be anticipated that drug
      induced upregulation of these intestinal pumps could reduce the oral
      bioavailability of imatinib, representing a novel mechanism of acquired
      pharmacokinetic drug resistance in cancer patients that are chronically treated
      with imatinib.

PMID- 15970669
TI  - Rewiring the exit from mitosis.
AB  - The mitotic cell cycle can be described as an alternation between two states.
      During mitosis, MPF (mitosis promoting factor) is high and keeps inactive its
      numerous molecular antagonists. In interphase, MPF is inactivated, and the
      antagonists prevail. The transition between the two states is ensured by 'helper'
      molecules that favor one state over the other. It has long been assumed that
      active MPF (a dimer of cyclin B and cyclin-dependent kinase 1) induces exit from
      mitosis by activating APC:Cdc20, a ubiquitin ligase responsible for cyclin B
      degradation. The molecular details have not been fully worked out yet, but recent
      results show that MPF and the ubiquitin ligase are not involved in a simple
      negative feedback loop. While it is proven that MPF activates APC, new data
      suggest that MPF inhibits Cdc20, i.e., that MPF and Cdc20 are antagonists. We
      introduce this new idea into a published model for cell cycle regulation in
      Xenopus laevis, and study its dynamical behavior. We show that the new wiring
      permits oscillations with a simpler and smaller network than previously envisaged
      and that the antagonism between MPF and Cdc20 suggests a new interpretation of
      the spindle checkpoint.

PMID- 15970670
TI  - TRAIL: at the center of drugable anti-tumor pathways.
AB  - Molecular analysis, in vivo and in vitro has identified TRAIL as a central
      component of anti-cancer networks in the cell. More recently, TRAIL has been
      shown to be involved in the selective apoptosis of AML cells by histone
      deacetylase inhibitors (HDACi). Here we summarize findings that the TRAIL pathway
      is a key factor in the apoptotic action of HDACi, as well as, retinoids and
      retinoid-combinations.

PMID- 15970671
TI  - The nonsteroidal anti-inflammatory drug Exisulind selectively induces apoptosis
      via JNK in secondary acute myeloid leukemia after myelodysplastic syndrome.
AB  - Treatment of patients suffering from myelodysplastic syndromes and secondary
      acute myeloid leukemia after MDS is often unsuccessful. Pro-apoptosis with
      arsenic trioxide has recently been proposed as a novel therapeutic approach.
      Exisulind is another potentially pro-apoptotic agent, and therefore, we
      investigated its influence on proliferation, differentiation, cell cycle and
      apoptosis in two sAML/MDS cell lines, one de-novo AML cell line and healthy CD34+
      bone marrow cells. Treatment of sAML/MDS cells with Exisulind clearly inhibited
      colony formation in the CFU-assays. Interestingly, Exisulind did not alter the
      percentages of sAML/MDS cells in G1-, G2-, M- or S-phase, but reduced
      proliferation and induced apoptosis in this cell type. Exisulind had no effect on
      de-novo AML or normal CD34+ cells. We detected increased c-Jun NH2-terminal
      kinase activity in sAML/MDS cells treated with Exisulind. Adding a specific JNK
      inhibitor to Exisulind-treated sAML/MDS cells partly abrogated apoptosis, thus
      proving that Exisulind-mediated apoptosis in sAML/MDS cells is dependent on JNK
      activation. We conclude that JNK is one mediator of apoptosis in sAML/MDS cells
      treated with Exisulind. Moreover, our data strongly suggests to explore the
      potential use of Exisulind as a novel, pro-apoptotic therapy for patients with
      MDS and sAML/MDS.

PMID- 15970672
TI  - Effector proteins for methylated histones: an expanding family.
AB  - Methylation of histone lysine residues in eukaryotic chromatin has been an
      exciting area of research ever since the first histone methyltransferase enzyme,
      Suv39h, was found to methylate lysine 9 of histone H3 in 2000. Only a year later,
      the HP1 chromodomain polypeptide was identified as a recognition module for this
      histone modification. Similar to bromodomain-containing proteins that recognize
      histone acetylation sites and subsequently stabilize large complexes to
      chromatin, effector proteins can also be recruited and stabilized by histone
      methylation. Although histone acetylation generally correlates with active
      transcription, histone methylation is associated with both the activation and
      silencing of transcription, depending on which lysine residue is modified. The
      list of proteins that may in fact directly associate with specific methylated
      histone lysines is expanding. Since the finding of HP1, many additional proteins
      have been shown to bind methylated histone residues. For instance, Polycomb,
      Chd1, 53BP1, and Crb2/Rad9 proteins all associate with methylated chromatin in a
      unique manner governed by their respective recognition motifs. Here we highlight
      recent data on the recognition specificity and biological significance of
      proteins that associate with methylated histone lysines.

PMID- 15970673
TI  - Hsp70-2 is required for tumor cell growth and survival.
AB  - Heat shock protein 70 (Hsp70) family consists of at least eight chaperone
      proteins that differ from each other by their pattern of expression and
      intracellular localization. Whereas ample experimental and clinicopathological
      data has implicated the major stress-inducible Hsp70-1 as a protein required for
      cancer cell survival, the study of the other family members has been limited by
      the lack of experimental tools to differentiate between the highly homologous
      family members. This limitation has been recently overcome by the RNA
      interference technology that for the first time allows targeted knockdown of the
      individual Hsp70 family members. Data based on this technology has revealed that
      also Hsp70-2, a protein essential for spermatogenesis, is required for cancer
      cell growth and survival. Remarkably, the highly homologous Hsp70 proteins
      enhance cancer cell growth and survival by distinct molecular mechanisms.

PMID- 15970674
TI  - TELAML1-positive ALL: a discordant genotype.

PMID- 15970675
TI  - VAV1: a new target in pancreatic cancer?
AB  - Pancreatic ductal adenocarcinoma (PDA) is arguably the most lethal malignancy in
      the United States. Despite the identification of many molecular alterations in
      PDA, this information has not translated into effective therapeutic strategies to
      date. A recent report in Cancer Cell (Fernandez-Zapico et al, Cancer Cell 2005,
      7:39-49) reveals an unexpected role for the hematopoietic-specific RhoGEF VAV1 in
      pancreatic tumorigenesis, where ectopic expression of VAV1 as a result of
      promoter demethylation was identified in the majority of established cell lines
      and PDA tissue samples. Importantly, VAV1 expression was functionally required
      for optimal proliferation, transformation and survival of pancreatic cancer cell
      lines. This study provides the first evidence of VAV1 promoter demethylation as
      an event in cancer progression, suggesting that aberrant signaling pathways
      driven by VAV1 are potential therapeutic targets in PDA.

PMID- 15970676
TI  - DMC: novel celecoxib derivatives to rap cancer.

PMID- 15970677
TI  - The cultured red blood cell: a study tool with therapeutic perspectives.

PMID- 15970678
TI  - High concentrations of retinoids induce differentiation and late apoptosis in
      pancreatic cancer cells in vitro.
AB  - BACKGROUND: Our previous investigations showed that retinoids, at specific
      concentrations, can inhibit cell proliferation. In this investigation, we
      hypothesize that high concentrations of retinoids can induce phenotypic changes
      (differentiation) and late apoptosis in pancreatic cancer cells in vitro.
      MATERIALS AND METHODS: To test our hypothesis, retinoid-induced differentiation
      was assessed: (1) phenotypically by light and electron microscopy and (2)
      biochemically by measuring carbonic anhydrase, aerobic metabolic and mucin
      producing activities. Modulation of transforming growth factor-beta (TGF-beta)
      and epidermal growth factor (EGF) autocrine pathways were utilized as mechanistic
      and differentiation markers. RESULTS: The extensive differentiation-indicative
      phenotypic changes correlated with several folds increase in the aerobic
      metabolism (MTT reduction and Mitochondrial mass), carbonic anhydrase activity
      and mucin production. There was a marked increase in TGF-beta (Bioassay and
      ELISA) and TGF-beta (RIA) secretion. EGF receptor density (Receptor binding
      assay) was reduced by 50% within six hours and was reflected on abolishment of
      EGFR ligand-induced proliferation. Cotreatment with the RAR-alpha antagonist,
      Ro41-5253 or pan-TGF-beta neutralizing antibody abolished the phenotypic and
      antiproliferative effects of all-trans retinoic acid. Apoptosis (TUNEL assay) was
      undetectable after three days of treatment with the maximum concentration used.
      However, apoptosis was extensively induced after six days of treatment.
      CONCLUSIONS: High concentrations of retinoids were able to induce phenotypic
      changes (differentiation) and late apoptosis in pancreatic cancer cells in vitro.
      The clinical ramifications of these observations await further investigations.

PMID- 15970679
TI  - Arabidopsis anaphase-promoting complexes: multiple activators and wide range of
      substrates might keep APC perpetually busy.
AB  - The anaphase-promoting complex (APC), a multisubunit E3 ubiquitin ligase, is an
      essential regulator of the cell cycle from metaphase until S phase in yeast and
      metazoans. APC mediates degradation of numerous cell cycle-related proteins,
      including mitotic cyclins and its activation and substrate-specificity are
      determined by two adaptor proteins, Cdc20 and Cdh1. Plants have multiple APC
      activators and the Cdh1-type proteins, in addition, are represented by two
      subclasses, known as Ccs52A and Ccs52B. The Arabidopsis genome contains five
      cdc20 genes as well as ccs52A1, ccs52A2 and ccs52B. In Schizosaccharomyces pombe,
      expression of the three Atccs52 genes elicited distinct phenotypes supporting
      nonredundant function of the AtCcs52 proteins. Consistent with these activities,
      the AtCcs52 proteins were able to bind both to the yeast and the Arabidopsis
      APCs. In synchronized Arabidopsis cell cultures the cdc20 transcripts were
      present from early G2 until the M-phase exit, ccs52B from G2/M to M while ccs52A1
      and ccs52A2 were from late M until early G2, suggesting consecutive action of
      these APC activators in the plant cell cycle. The AtCcs52 proteins interacted
      with different subsets of mitotic cyclins, in accordance with their expression
      profiles, either in free- or CDK-bound forms. Expression of most APC subunits was
      constitutive, whereas cdc27a and cdc27b, corresponding to two forms of apc3, and
      ubc19 and ubc20 encoding E2-C type ubiquitin-conjugating enzymes displayed
      differences in their cell cycle regulation. These data indicate the existence of
      numerous APC(Cdc20/Ccs52/Cdc27) forms in Arabidopsis, which in conjunction with
      different E2 enzymes might have distinct or complementary functions at distinct
      stages of the cell cycle.

PMID- 15970680
TI  - Overcoming acquired resistance to Iressa/Tarceva with inhibitors of a different
      class.
AB  - Small molecule kinase inhibitors of the epidermal growth factor receptor (EGFR)
      have recently been found to exhibit clinical efficacy in the setting of nonsmall
      cell lung cancers that harbor activating EGFR mutations. However, the remissions
      induced by these drugs (Iressa and Tarceva) are typically short-lived, presumably
      due to acquired drug resistance. We recently reported findings demonstrating that
      a distinct class of EGFR inhibitors may overcome some mechanisms of secondary
      drug resistance in these tumors and may therefore be useful in treating lung
      cancer patients that initially responded to Iressa or Tarceva and eventually
      relapsed.

PMID- 15970681
TI  - When all colonies are blue.

PMID- 15970682
TI  - Analysis of fibronectin expression in the bilharzial granulomas and of laminin in
      the transformed urothelium in schistosoma haematobium infested patients.
AB  - The bilharzial granulomas and urothelial transformation are common findings in
      Schistosoma haematobium infested patients. We hypothesize that the distribution
      of extrinsic (fibronectin, FN) and intrinsic basement membrane (BM) proteins
      (laminin, LN) is altered during the evolution of these lesions. METHODS: To test
      this hypothesis, 70 cystectomy specimens, entailing variable associations of
      normal and dysplastic urothelium (all cases), and bilharzial granulomas were
      examined for FN and LN protein expression. RESULTS: The biharzial granulomas were
      formed of admixture of CD3+T cells, CD68+histiocytes and CD220B cells. The CD3+T
      cells and and CD68+histiocytes were the predominant cell populations. Increased
      deposition of FN occurred with the evolution from cellular (loose fibrillary
      network, 20 cases) to fibrocellualr (dense fibrillary network, 30 cases) to
      fibrotic (tight conglomerates, 20 cases) granulomas. Alternatively, BM staining
      for LN was linear and continuous underlying normal and metaplastic urothelium. In
      dysplastic urothelium (20 cases), it showed breaks in continuity. CONCLUSIONS:
      Alterations of FN and LN occur during the development of the bilharzial granuloma
      and urothelial transformation.

PMID- 15970683
TI  - A new Perp in the lineup: linking p63 and desmosomal adhesion.
AB  - The process of stratified epithelial development depends upon a transcriptional
      program directed by the p53-related transcription factor p63. p63 is required for
      the commitment of the ectoderm to stratification and for the completion of
      terminal differentiation in stratified epithelia, and mutations in p63 have been
      identified in multiple developmental disorders affecting ectoderm-derived
      tissues. Recent work from our laboratory has determined that the p53 target gene
      Perp is required for the integrity of the stratified epithelia specified by p63,
      and that expression of Perp in these structures depends on the presence of p63.
      In these tissues, Perp is a critical component of the desmosome, a cell-cell
      adhesion complex whose constituents are frequently mutated in human diseases
      affecting the skin and hair. Perp's position downstream of p63 and p53, as well
      as its essential role in normal desmosome function, suggest that it, like other
      adhesion proteins, may be a target for mutation in human blistering diseases or
      cancer.

PMID- 15970684
TI  - FEAR but not MEN genes are required for exit from meiosis I.
AB  - Exit from mitosis is regulated by Cdc14, which plays an essential role in
      triggering cyclin-dependent kinase inactivation. Throughout most of the cell
      cycle, Cdc14 is sequestered in the nucleolus where it remains inactive. After the
      completion of anaphase, an essential signaling cascade, named the Mitotic Exit
      Network, or MEN, promotes Cdc14 release. Cdc14 is also released from the
      nucleolus in early anaphase by another, nonessential, pathway called FEAR
      (CdcFourteen Early Anaphase Release). Separase (Esp1), polo kinase (Cdc5), the
      kinetochore protein Slk19, and Spo12, whose molecular function remains unknown,
      have been identified as members of the FEAR pathway. In meiosis, mutations in
      CDC14 and its FEAR pathway regulators, CDC5, SLK19, and SPO12, all result it asci
      that contain only two diploid spores because of a defect in the ability to exit
      meiosis I. Thus although the FEAR pathway is dispensible for mitotic exit, it is
      essential for meiosis I exit. The way that the genes of the Mitotic Exit Network
      contribute to coordinating meiotic progression is less clear. Here, we explore
      this issue. Our results demonstrate that the orderly transition from meiosis I to
      meiosis II is accomplished by eliminating MEN function and using the FEAR pathway
      to modulate cyclin dependent kinase activity, in part through the actions of
      SIC1.

PMID- 15970685
TI  - Osteopontin influences the invasiveness of pancreatic cancer cells and is
      increased in neoplastic and inflammatory conditions.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive
      malignancies, with an overall 5-year survival rate of less than 5%. Invasive
      tumor growth and early metastasis are two important reasons for this dismal
      prognosis. Osteopontin (OPN) is a secretory protein with a variety of functions,
      for example in cell adhesion and migration, inflammatory reaction and apoptosis.
      In this study the functional role of OPN in human pancreatic cancer and its
      potential use as a disease marker were analyzed. By real time quantitative PCR,
      there was a 2.2-fold and 1.6-fold increase of OPN mRNA in pancreatic cancers (n =
      23) and chronic pancreatitis samples (n = 22), respectively, compared to normal
      pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN
      staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and
      liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer
      patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n
      = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and
      a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN
      significantly increased the invasiveness of pancreatic cancer cells, without
      having any impact on cell proliferation. In addition, down regulation of OPN by
      specific siRNA molecules decreased pancreatic cancer cell invasion. In
      conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis
      patients are not significantly different, thereby restricting its role as a
      prognostic or follow-up marker. Our results do suggest, however, that blockade of
      OPN might be useful as a therapeutic approach to inhibit invasion and metastasis
      of pancreatic cancer cells.

PMID- 15970686
TI  - Repair of ischemic heart disease with novel bone marrow-derived multipotent stem
      cells.
AB  - Congestive heart failure is a growing, worldwide epidemic. The major causes of
      heart failure are related to irreversible damage resulting from myocardial
      infarction (heart attack). The long-standing axiom has been that the myocardium
      has a limited capacity for self-repair or regeneration; and the irreversible loss
      of cardiac muscle and accompanying contraction and fibrosis of myocardial scar
      tissue, sets into play a series of events, namely, progressive ventricular
      remodeling of nonischemic myocardium that ultimately leads to progressive heart
      failure. The loss of cardiomyocyte survival cues is associated with diverse
      pathways for heart failure, underscoring the importance of maintaining the number
      of viable cardiomyocytes during heart failure progression. Currently, no
      medication or procedure used clinically has shown efficacy in replacing the
      myocardial scar with functioning contractile tissue. Therefore, given the major
      morbidity and mortality associated with myocardial infarction and heart failure,
      new approaches have been sought to address the principal pathophysiologic
      deficits responsible for these conditions, resulting from the loss of
      cardiomyocytes and viable blood vessels. Recently, the identification of stem
      cells from bone marrow capable of contributing to tissue regeneration has ignited
      significant interest in the possibility that cell therapy could be employed
      therapeutically for the repair of damaged myocardium. In this review, we will
      discuss the currently available bone marrow-derived stem progenitor cells for
      myocardial repair and focus on the advantages of using recently identified novel
      bone marrow-derived multipotent stem cells (BMSC).

PMID- 15970687
TI  - AKT activation and response to interferon-beta in human cancer cells.
AB  - Significant growth inhibition and induction of apoptosis by IFN-beta in cancer
      cells including colorectal cancer cells have been observed. We and others have
      previously reported the Stat 1 induction of TRAIL is a crucial step in the IFN
      beta induced apoptosis pathway. However, when evaluating the sensitivity of a
      panel of colorectal cancer cell lines, we found no clear correlation between
      activation of the Jak/Stat signaling pathway and response to interferon. In the
      present study, we have evaluated the interaction of the PI3k/Akt pathway and IFN
      beta induced apoptosis in human colorectal cancer cells. The results demonstrate
      a correlation between Akt activity, phosphorylation of Bad and resistance to
      interferon-induced apoptosis in these cells. The association of activation of
      Akt, phosphorylation of Bad and resistance to IFN-beta-induced apoptosis was
      further supported by the observation that disruption of the pathway in a more
      resistant cell line led to sensitization, and expression of an activated Akt in a
      more sensitive cell line led to increased resistance. Taken together, this data
      indicates that the PI3/Akt kinase pathway may be an important contributor to IFN
      beta sensitivity and resistance in colorectal cancer cells. This data
      demonstrates a potential pathway by which cells may develop resistance to IFN,
      and further elucidation of this process may allow us to better target IFN
      therapy.

PMID- 15970688
TI  - Inhibition of basigin expression in glioblastoma cell line via antisense RNA
      reduces tumor cell invasion and angiogenesis.
AB  - Basigin/CD147, also named extracelluar matrix metalloproteinase inducer
      (EMMPRIN), has been implicated in playing very important roles in several aspects
      of tumor progression. In this study, we examined the inhibitory effects of
      antisense RNA of CD147 on invasion and angiogenesis of human glioblastoma U251
      cells in vitro. The U251 cell line was transfected by a plasmid containing
      antisense CD147 cDNA. Gelatin zymography was used to determine the effect on
      reducing secretions of MMP-2 and MMP-9 of the transfected cells. Boyden chamber
      was employed to test the invasion of U251 cells in vitro. We found that
      downregulation of CD147 resulted in reducing secretions of MMP-2, MMP-9, and
      VEGF. Moreover, the invasion of stable antisense transfectants was inhibited.
      Wound-induced migration assay also showed decreased migration in stable antisense
      transfectants compare to parental- and empty vector-transfected cells. Taken
      together, these results provide evidence that invasion of human glioblastoma
      cells can be inhibited by antisense RNA of CD147. Basigin/CD147 may be used as a
      potential target of drugs for anti-invasion and metastasis of human glioblastoma
      cells.

PMID- 15970689
TI  - Reversal of the ATM/ATR-mediated DNA damage response by the oncogenic phosphatase
      PPM1D.
AB  - The eukaryotic cell has evolved a sophisticated set of cell signaling pathways
      that respond to DNA damage and efficiently repair that damage, protecting the
      cell from deleterious mutations, genomic instability, and transformation into a
      cancerous state. The ATM and ATR serine/threonine kinases are key sensors and
      transducers of DNA damage signals through phosphorylation of an array of
      signaling molecules that mediate all aspects of the DNA damage response,
      including enforcement of cell cycle checkpoints and direct repair of damaged DNA.
      We have shown that a type 2C serine/threonine phosphatase, PPM1D (or Wip1), can
      reverse the phosphorylation status of ATM/ATR-phosphorylated proteins p53 and
      Chk1. This dephosphorylation of p53 and Chk1 by PPM1D may result in reduced
      functional activities and is accompanied by suppression of DNA damage-induced
      cell cycle checkpoints and some aspects of DNA repair. Because PPM1D is
      transcriptionally activated by p53 in response to DNA damage, PPM1D may serve as
      a critical component of a p53 negative feedback regulatory loop since it now
      appears that PPM1D can inhibit p53 activity by at least four different molecular
      mechanisms. This may explain why PPM1D is amplified and overexpressed in a subset
      of human breast cancers that invariably retain wild type p53 alleles. We
      hypothesize that PPM1D is a homeostatic regulator of the DNA damage response that
      returns the cell to a more normal unstressed state following repair of the
      damage.

PMID- 15970690
TI  - The PAL-mechanism of chromosome maintenance: causes and consequences.
AB  - It is generally accepted that cells with extensive, un-repaired DNA damage can
      escape cell cycle arrest only by disabling checkpoint pathways and they usually
      perish, after several divisions, presumably due to catastrophic events on their
      chromosomes. Our recently discovered PAL-mechanism opens a new perspective, that
      some eukaryotic cells with short chromosome ends (telomeres), usually detected as
      DNA damage, can escape permanent cell cycle arrest (senescence) under special
      conditions, despite having intact checkpoints and even immortalize, despite
      lacking telomerase or other telomere elongation mechanisms. Here we present the
      first evidence that telomerase-lacking, senescent cells generate DNA damage
      (single stranded DNA) at internal chromosomal regions, while the telomere
      proximal single stranded DNA appears to be either lost or repaired. This first
      evidence is from the budding yeast model system. We also discuss the possible
      involvement of the PAL-mechanism in carcinogenesis.

PMID- 15970691
TI  - Aberrant methylation of the Human Hedgehog interacting protein (HHIP) gene in
      pancreatic neoplasms.
AB  - Hedgehog pathway overactivity has been implicated in the development of a variety
      of human cancers. The Human Hedgehog interacting protein (HHIP), a negative
      regulator of hedgehog signaling, has been shown to be underexpressed in
      pancreatic cancers. In this study we determined if the HHIP gene is a target for
      genetic and epigenetic alterations. While no mutations of HHIP were identified,
      we found complete methylation of the HHIP promoter CpG island in three pancreatic
      cancer cell lines, and partial hypermethylation in 13/17 (80%) pancreatic cancer
      cell lines, 35/75 (46%) primary pancreatic cancers and 14/18 (78%) pancreatic
      cancer xenografts, but no methylation in 13 normal pancreata. In pancreatic
      cancer cell lines, complete methylation was associated with absent or reduced
      HHIP expression by real-time RT-PCR. HHIP expression could be restored in
      methylated cell lines using epigenetic modifier drugs. Restoring the expression
      of HHIP in pancreatic cancer cells by 5-aza-2'-deoxycytidine led to a decrease in
      Gli reporter activity, consistent with downregulation of Hedgehog signaling.
      These results indicate in some pancreatic adenocarcinomas that HHIP is
      epigenetically inactivated by promoter methylation, and its silencing could
      contribute to the increased Hedgehog signaling observed in pancreatic neoplasms.

PMID- 15970692
TI  - New end take off: regulating cell polarity during the fission yeast cell cycle.
AB  - Cell polarization is a major event of the cell cycle and underlies the function
      of most cells. Cell polarity is often achieved through the coordinated
      organization of the microtubule and act in cytoskeletons. Dramatic changes in
      cell polarization occur during the cell cycle and are subject to regulation by
      cell cycle controls. Cells of the fission yeast Schizosaccharomyces pombe grow by
      tip extension in a cell cycle-controlled manner. During G2 phase, these cells
      exhibit a transition in cell polarization known as New End Take Off (NETO), in
      which monopolar cells initiate bipolar growth. Dynamic microtubules contribute to
      this process by depositing at cell ends the microtubule plus end proteins tea1p
      and tea4p, which are necessary for NETO. We discuss here how these proteins may
      recruit for 3p, a formin responsible for actin nucleation, as well as two other
      actin binding proteins, bud6p and sla2p, to initiate cell polarization at the new
      end of the cell. Thus, the study of NETO is revealing a mechanism by which the
      plus ends of microtubules regulate the spatial organization of actin.

PMID- 15970693
TI  - Upping the bid on engineered inducible cell death.

PMID- 15970694
TI  - The function of the Drosophila caspase DRONC in cell death and development.
AB  - dronc, the only apical caspase in Drosophila, is thought to be essential and non
      redundant for apoptosis. Recent analyses of several independently derived dronc
      mutants have demonstrated that DRONC is required for normal development.
      Interestingly, analysis of these mutants show that DRONC is not essential for
      cell death in all tissues and that in some cases, DRONC-independent effector
      caspase activation and apoptosis can occur. These mutants provide a valuable
      resource to investigate the recently reported roles of DRONC in nonapoptotic
      pathways. Insights gained from the dronc mutants will help in advancing our
      understanding of caspase function in various developmental pathways.

PMID- 15970695
TI  - Targeted gene delivery by intravenous injection of retroviral vectors.
AB  - Specifically and effectively directing a therapeutic gene to its intended site of
      action is a critical issue for translation of basic genomics to clinical gene
      therapy. Delivering gene therapy vectors to specific cells or tissues through
      intravenous injection is the most desirable method for this purpose. In 2001, we
      reported successful targeted gene transduction in vitro utilizing both
      oncoretroviral and lentiviral vectors pseudotyped with a chimeric Sindbis virus
      envelope (ZZ SINDBIS). However, these pseudotypes mediated nonspecific gene
      transduction to liver and spleen in vivo. To address this problem we generated
      the modified ZZ SINDBIS (termed m168) with significantly less nonspecific
      infectivity. To investigate the ability of m168 pseudotyped lentiviral vector to
      mediate targeted gene transduction in vivo, we utilized a metastatic tumor model
      by using mouse melanoma cells engineered to express human P-glycoprotein. We
      administered the m 168 pseudotyped vector conjugated with anti-P-glycoprotein
      antibody into the mice intravenously to target metastatic melanoma. The m168
      pseudotyped vector selectively infected metastatic melanoma cells demonstrating
      successful targeted gene transduction in vivo. Targeting technology based upon
      m168 can be further modified for application not only to cancer but also
      potentially to genetic, neurologic, infectious and immune diseases, thereby
      expanding the future application of gene therapy.

PMID- 15970696
TI  - A nuclear targeting determinant for SATB1, a genome organizer in the T cell
      lineage.
AB  - SATB1 is a nuclear protein, which acts as a cell-type specific genome organizer
      and gene regulator essential for T cell differentiation and activation. Several
      functional domains of SATB1 have been identified. However, the region required
      for nuclear localization remains unknown. To delineate this region, we employed
      sequence analysis to identify phylogenetically diverse members of the SATB1
      protein family, and used hidden Markov model (HMM)-based analysis to define
      conserved regions and motifs in this family. One of the regions conserved in
      SATB1- and SATB2-like proteins in mammals, fish, frog and bird, is located near
      the N-terminus of family members. We found that the N-terminus of human SATB1 was
      essential for the nuclear localization of the protein. Furthermore, fusing
      residues 20-40 to a cytoplasmic green fluorescence protein (GFP) fused to
      pyruvate kinase (PK) was sufficient to quantitatively translocate the pyruvate
      kinase into the nucleus. The nuclear targeting sequence of human SATB1 (residues
      20-40) is novel and does not contain clusters of basic residues, typically found
      in 'classical' nuclear localization signals (NLSs). We investigated the
      importance of four well-conserved residues (Lys29, Arg32, Glu34, and Asn36) in
      this nuclear targeting sequences. Remarkably, full-length SATB1 harboring a
      single point mutation at either Lys29 or Arg32, but not Glu34 or Asn36, did not
      enter the nucleus. Our results indicate that SATB1 N-terminal residues 20-40
      represent a novel determinant of nuclear targeting.

PMID- 15970697
TI  - Maintenance of epigenetic memory in cloned embryos.
AB  - Different cell types have characteristic patterns of gene expression. Once a cell
      has differentiated, its daughter cells nearly always differentiate in the same
      way. The maintenance of cell lineage involves either instructions from a cell's
      surroundings or the inheritance of memory from a parent cell. In normal
      development, the differentiation state of a cell is remarkably stable and
      irreversible. However the transplantation of a somatic cell nucleus to an
      enucleated egg often leads to a complete reprogramming of gene expression. We
      summarize here the results of some Amphibian nuclear transfer experiments that
      reveal a memory of gene expression. This and some other experiments exemplify
      epigenetic memory that persists through many cell divisions. In the case of
      nuclear transfer experiments, the actively transcribed state of a gene can be
      propagated through many cell divisions in the absence of the stimulus that first
      induced the activity of this gene. We discuss the possible basis of these two
      examples of persistent epigenetic memory, namely changes at DNA methylation, and
      histone modifications.

PMID- 15970698
TI  - Adenovirus overrides cellular checkpoints for protein translation.
AB  - mTOR is a critical regulator of protein translation, and plays an important role
      in controlling cellular replication. Recent studies indicate that nutrient and
      growth factor mediated activation of mTOR is deregulated in human cancer, and
      therefore represents an attractive tumor target. However, activation of mTOR is a
      complex process that is not yet fully understood. DNA viruses and tumor cells
      often perturb similar cellular pathways to facilitate their replication. In a
      recent study, we used adenovirus as a novel tool to probe the mechanisms
      underlying the inappropriate activation of mTOR upon virus infection of quiescent
      primary cells. These studies revealed that adenovirus encodes two viral proteins,
      E4-ORF1 and E4-ORF4, which activate mTOR, even in the absence of nutrient/growth
      factor signals, and which play a role in promoting viral replication. E4-ORF1
      mimics growth factor signaling to mTOR by activating PI3-kinase, whereas E4-ORF4,
      which binds and relocalizes PP2A, can substitute for glucose mediated activation
      of mTOR. We discuss insights from this study, together with the similarities that
      may exist between viruses and tumor cells with respect to the mechanistic and
      functional requirements for mTOR activation in driving their aberrant DNA
      replication.

PMID- 15970699
TI  - PTEN loss inhibits CHK1 to cause double stranded-DNA breaks in cells.
AB  - CHK1 is an essential kinase involved in the regulation of the cell cycle
      progression and preservation of genomic integrity. Inhibition of CHK1 leads to
      the accumulation of double-stranded DNA breaks. Loss of PTEN impairs CHK1
      mediated checkpoint activation due to cytoplasmic sequestration of ubiquitinated
      CHK1. Here, we provide evidence that another consequence of reduced CHK1 function
      in PTEN deficient cells is the accumulation of double-stranded DNA breaks.
      Moreover, we show that the site of CHK1 ubiquitination (K274) is near the site of
      AKT phosphorylation (S280). Overall, these data demonstrate that lack of PTEN
      generates DNA damage due to inappropriate inactivation of CHK1.DNA damage due to
      the loss of PTEN is likely to stimulate tumor development.

PMID- 15970700
TI  - Mad3/BubR1 phosphorylation during spindle checkpoint activation depends on both
      Polo and Aurora kinases in budding yeast.
AB  - During mitosis the spindle assembly checkpoint (SAC) delays the onset of anaphase
      and mitotic exit until all chromosomes are bipolarly attached to spindle fibers.
      Both lack of attachment due to spindle/kinetochore defects and lack of tension
      across kinetochores generate the "wait anaphase" signal transmitted by the SAC,
      which involves the evolutionarily conserved Mad1, Mad2, Mad3/BubR1, Bub1, Bub3
      and Mps1 proteins, and inhibits the activity of the ubiquitin ligase Cdc20/APC,
      that promotes both sister chromatid dissociation in anaphase and mitotic exit. In
      particular, Mad3/BubR1 is directly implicated, together with Mad2, in Cdc20
      inactivation in both human and yeast cells, suggesting that its activity is
      likely finely regulated. We show that budding yeast Mad3, like its human
      orthologue BubR1, is a phosphoprotein that is hyperphosphorylated during mitosis
      and when SAC activation is triggered by microtubule depolymerizing agents,
      kinetochore defects or lack of kinetochore tension. In vivo Mad3 phosphorylation
      depends on the Polo kinase Cdc5 and, to a minor extent, the Aurora B kinase Ipl1.
      Accordingly, replacing with alanines five serine residues belonging to Polo
      kinase-dependent putative phosphorylation sites dramatically reduces Mad3
      phosphorylation, suggesting that Mad3 is likely an in vivo target of Cdc5.

PMID- 15970701
TI  - 53BP1 is a positive regulator of the BRCA1 promoter.
AB  - Germline mutations in the BRCA1 tumor suppressor gene contribute to familial
      breast and ovarian tumor formation. Sporadic breast and ovarian cancer, however,
      which accounts for more than 90% of total cases and virtually lacks BRCA1
      mutations, exhibits reduced expression of the BRCA1 gene. The magnitude of this
      reduction correlates with disease progression. In this report we have identified
      an imperfect palindrome sequence for binding of the 53BP1-containing complex, 
      40TTCCGTGG CAACGGAA-25, within the BRCA1 minimal promoter. Over expression of
      53BP1 activates a luciferase reporter driven by the wild type BRCA1 minimal
      promoter, but not by the BRCA1 minimal promoter with mutated palindrome sequence.
      Depletion of endogenous 53BP1 by siRNA suppresses activity of the BRCA1 minimal
      promoter. In vitro and in vivo DNA-protein interaction studies demonstrate that
      this palindrome sequence binds to the 53BP1-containing complex. These findings
      establish a positive regulation of the BRCA1 promoter by 53BP1. Disruption of
      this regulation in cancer cells may provide a molecular mechanistic basis for
      sporadic breast and ovarian tumor formation.

PMID- 15970702
TI  - Sugar recognition and metastasis: from birth of a research field to the clinic.

PMID- 15970703
TI  - In vivo studies of pharmacokinetics and efficacy of Bismuth-213 labeled
      antimelanoma monoclonal antibody 9.2.27.
AB  - OBJECTIVES: Key objectives of the study were to determine the pharmacokinetics
      and efficacy of the alpha emitting Bismuth-213 labeled 9.2.27 alpha
      immunoconjugate (AIC). METHODS: Balb/c nude mice were injected with varying doses
      of AIC to determine the pharmacokinetics of the AIC. The results were normalized
      to percent counts per minute (CPM) per gram per 3.7 MBq of the AIC
      (%CPM/g/3.7MBq) for each organ. Efficacy was determined by injected varying doses
      of AIC to different stages of tumor growth for intra-lesional, systemic and
      multiple dose TAT. RESULTS: Biodistribution studies showed similar
      pharmacokinetics for blood and brain, liver, kidneys, spleen, gut, heart, lungs
      and bone marrow, indicating that there was no retention of AIC. This is
      particularly important for brain (due to the presence of NG2+ cells) as the
      antibody 9.2.27 may reach NG2 positive cells. Tumor growth at 2-days post
      inoculation was completely inhibited by TAT. The response to TAT was inversely
      proportional to tumor growth, i.e., a reduction in response was observed with
      increased tumor burden. A multiple dose regime was found to be more effective
      than single dose. CONCLUSIONS: TAT is effective for the treatment of
      micrometastatic melanoma, when the tumor is preangiogenic in the form of isolated
      cells or cell clusters. There is no evidence of retention of AIC in brain,
      kidneys and other vital organs.

PMID- 15970704
TI  - ARF the integrator: linking NF-kappaB, p53 and checkpoint kinases.
AB  - The ARF tumor suppressor initiates the cellular response to aberrant oncogene
      activation through binding to and inhibiting the activity of Hdm2/Mdm2, the
      inhibitor of p53. However, many pathways also active in the cell will oppose p53
      function if left unchecked. An example of this, is the RelA (p65) NF-kappaB
      subunit. Frequently activated by oncogenes, RelA is a potent inducer of anti
      apoptotic gene expression, which has the potential to inhibit the pro-apoptotic
      functions of p53. We have recently discovered that by inducing the activity of
      the checkpoint kinases ATR and Chk1, ARF neutralises this opposing pathway. ARF
      induced Chk1 phosphorylates RelA on threonine 505, a residue in its
      transactivation domain, thus inhibiting NF-kappaB's ability to stimulate anti
      apoptotic gene expression. Furthermore, ARF-induced ATR is required for efficient
      induction and activation of p53. We propose that this pathway will target other
      proteins with pro-proliferative or anti-apoptotic functions. Therefore, through
      this mechanism, ARF can integrate the cellular response to an oncogene, thus
      maximising the effectiveness of the p53 tumor suppressor pathway.

PMID- 15970705
TI  - JAK2 in myeloproliferative disorders is not just another kinase.
AB  - Myeloproliferative disorders (MPD) represent a subcategory of hematological
      malignancies and are characterized by a stem cell-derived clonal proliferation of
      myeloid cells including erythrocytes, platelets, and leucocytes. Traditionally,
      the term 'MPD' included chronic myeloid leukemia (CML), polycythemia vera (PV),
      essential thrombocythemia (ET), and myelofibrosis with myeloid metaplasia (MMM).
      At present, these four disorders are referred to as 'classic' MPD and are
      distinguished from a spectrum of other MPD-like clinicopathologic entities that
      are operationally classified as 'atypical' MPD. The oncogenic mutations(s) in
      classic MPD are unknown except for CML, which is associated with an activating
      mutation (Bcr/Abl) of the gene encoding for the Abl cytoplasmic protein kinase
      (PTK). In the last 3 months, a somatic point mutation of JAK2 (JAK2(V617F)), the
      gene encoding for another cytoplasmic PTK was reported in the majority of
      patients with PV and approximately half of those with either ET or MMM. The same
      mutation was also found in a small number of patients with either atypical MPD or
      the myelodysplastic syndrome but not in normal controls, germline tissue
      including T lymphocytes, and patients with secondary erythrocytosis. In vitro,
      JAK2(V617F) was associated with constitutive phosphorylation of JAK2 and its
      downstream effectors as well as induction of erythropoietin hypersensitivity in
      cell lines. In vivo, murine bone marrow transduced with a retrovirus containing
      JAK2(V617F) induced erythrocytosis in the transplanted mice. Taken together,
      these observations suggest that JAK2(V617F) is an acquired myeloid lineage
      specific mutation that engenders a pathogenetic relevance for the PV phenotype in
      MPD.

PMID- 15970706
TI  - Inhibition of experimental colon cancer metastasis by the GABA-receptor agonist
      nembutal.
AB  - Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter, and GABA
      receptors have been recently detected on epithelial colon cancer cells. Nembutal
      (pentobarbital) is a barbiturate with GABA-agonistic effects. We demonstrate that
      GABA receptors are present on colon cancer cell lines (KM12SM, HT29, RKO).
      Nembutal (0.1-500 microg/ml) continuous exposure resulted in an IC50 level of 58
      microg/ml for the KM12SM cells and 120 microg/ml for the HT29 cells. Nembutal
      reduced cellular cAMP concentration in colon cancer cells and resulted in a dose
      and time dependent decrease in MMP-2 and MMP-9 levels. In the KM12SM intracecal
      injected mice, 9 of 10 mice in the metaphane group developed a primary tumor
      (mean weight = 2.16 g +/- 0.76) compared to 7 of 10 mice in the nembutal group
      (mean weight = 0.41 g +/- 0.21, p = 0.03). In the KM12SM intrasplenic injected
      mice, the tumor weight in the spleen was 85% smaller in the nembutal group
      compared to the metaphane group (p = 0.008). In the HT29 injected mice, the
      metaphane group and nembutal group had similar tumor incidence, but combined
      tumor weight (primary tumor and liver metastases) was significantly higher in the
      metaphane group (1.61+/- 0.45 g) versus 0.07 +/- 0.05 g; p = 0.008. The incidence
      of liver metastases in the nembutal group was zero compared to eight out of nine
      in the metaphane group. To the best of our knowledge, this is the first evidence
      that nembutal is a potent inhibitor of primary colon cancer and metastasis. These
      findings may have therapeutic implications for the treatment of colon and other
      cancers.

PMID- 15970707
TI  - Genetic instability: the dark side of the hypoxic response.
AB  - Under low oxygen tension, the activated transcription factor HIF-1alpha
      upregulates an array of hypoxia-inducible genes via heterodimerization with ARNT
      and binding to the hypoxia-responsive element in the promoter. Alternatively, HIF
      1alpha regulates hypoxia-responsive genes by functionally antagonizing the
      oncoprotein Myc via protein-protein interactions. This so-called HIF-1alpha-Myc
      mechanism apparently not only accounts for the gene upregulation, but also for
      the gene downregulation during hypoxia, depending upon the activating and
      repressive nature of Myc in gene expression. Indeed, our recent study
      demonstrated that both mismatch repair genes, MSH2 and MSH6, are inhibited by
      this mechanism in a p53-dependent manner. In particular, the constitutively bound
      transcription factor Sp1 serves as a molecular switch by recruiting HIF-1alpha in
      hypoxia to displace the transcription activator Myc from the promoter. Therefore,
      our findings shed light on the mechanisms underlying hypoxia-induced genetic
      instability, an "adverse"effect of the hypoxic response, and yet a germane
      process to tumor survival and progression.

PMID- 15970708
TI  - Cell division and hematopoietic stem cells: not always exhausting.
AB  - Pluripotent hematopoietic stem cells (HSCs) sustain blood cell production
      throughout an individual's lifespan through complex processes supported by self
      renewal, differentiation, senescence or cell death decisions of the HSCs. These
      decisions are tightly regulated under homeostatic conditions, allowing both the
      continuous generation of progenitors and mature cells in addition to the
      maintenance and replenishment of the HSC pool. Several recent studies have
      provided insights into some of the key molecular mechanisms regulating these
      different cell fate decisions. One of the emerging themes of these studies is
      that of the importance of cell cycle regulators in the maintenance of HSCs.

PMID- 15970709
TI  - Changes in survivin messenger RNA level during chemotherapy treatment in ovarian
      cancer cells.
AB  - OBJECTIVE: To investigate the role of antiapoptosis gene, survivin involved in
      regulating cell sensitivity to taxanes and platinum compounds. METHODS: Cultured
      human epithelial ovarian cancer cell line A2780 and its platinum(DDP)-resistance
      cell line A2780/DDP were divided into three groups as control, treatment with
      DDP, and treatment with Taxol Expression of mdr1 and survivin genes in each group
      was detected by using reverse transcription-polymerase chain reaction (RT-PCR).
      Apoptosis in the ovarian cancer cell lines was measured by flow cytometry.
      RESULTS: After treatment with DDP for 48 h, relative survivin expression was
      significantly lower than that of no drug given (p<0.05). In A2780/DDP cells,
      expression of Survivn was obviously higher than that of the control group
      (P<0.05) after treatment of DDP for 48 h. Interestingly, survivin mRNA level was
      significantly decreased after treatment with Taxol for 48 h in the A2780/DDP
      Taxol group compared with that in the control group. Apoptosis rate of A2780
      cells was significantly increased to 46.21% and 44.46%, respectively, with
      treatment of DDP and Taxol. However, apoptosis rate in A2780/DDP was only 20.04%
      after DDP treatment for 48 h, demonstrating the presence of resistance to DDP in
      A2780/DDP cells. CONCLUSIONS: This study demonstrated that changes in survivin
      mRNA level were related to the chemotherapy-induced apoptosis. Survivin may be
      considered as a biological indicator of the chemo-resistance of ovarian cancer.

PMID- 15970710
TI  - Intestinal metaplasia with a high salt diet induces epithelial proliferation and
      alters cell composition in the gastric mucosa of mice.
AB  - Intestinal metaplasia of the gastric mucosa is an important component in the
      pathway to adenocarcinoma. The mechanisms that induce the progression from
      intestinal metaplasia to cancer have not been elucidated. High dietary salt has
      been known as one of the risk factors for gastric cancer development in humans.
      Therefore, we investigated the role of high salt diet on gastric epithelial cell
      proliferation and differentiation, using our mouse model that ectopically
      expressed Cdx2 homeodomain transcription factor and induced an intestinal
      metaplastic phenotype in the gastric epithelia. Sixty Cdx2 transgenic and sixty
      age-matched wild-type littermates were studied. Fifty-percent Cdx2 transgenic and
      wild type mice were administered a high-salt diet and the other fifty-percent was
      fed a standard diet starting at 12 weeks after birth. At 10, 20 and 40 weeks
      after initiation of the diets, histopathological changes were determined by
      Hemotoxylin and Eosin, alcian blue, and periodic acid-Schiff (PAS) staining. Cell
      types and cell kinetics were assessed by immunohistochemistry. At 52 weeks,
      significant alterations in pathology were observed in the Cdx2 transgenic mice
      fed a high-salt diet, including elongation of gastric pits, reduction of the
      glandular zone in the gastric corpus, and deepening of glands in the antrum. In
      the Cdx2 transgenic mice fed a high salt diet, the parietal and chief cells were
      significantly decreased in the gastric corpus. A significant increase in cell
      proliferation and apoptosis in the corpus and antrum were observed in Cdx2
      transgenic mice fed a high-salt diet as compared to wild-type littermates. Taken
      together, these data implicate that intestinal metaplasia in concert with a high
      salt diet induces epithelial proliferation, apoptosis, and alters cellular types
      in the gastric mucosa of mice. Alteration in the composition of the gastric
      epithelium may play a role in influencing the microenvironment to engender
      susceptibility to carcinogens.

PMID- 15970711
TI  - Modeling resistance to pathway-targeted therapy in ovarian cancer.
AB  - A detailed understanding of the biochemical pathways that are responsible for
      cancer initiation and maintenance is critical to designing targeted cancer
      therapy. Although we have accumulated knowledge about individual molecular
      changes that underlie cancer development, we are still learning how multiple
      biochemical pathways cooperate in cancer. This cooperation and cross-talk between
      redundant biochemical pathways appear to be the main reasons for the failure of
      therapeutic agents that are designed to interfere with a specific molecular
      target. In order to simulate the cooperation of several biochemical pathways in
      cancer development, we have engineered mouse ovarian cancer cell lines and tumors
      with different combinations of defined genetic alterations. We have used this
      system to determine the functional contributions of individual pathways that are
      necessary for cell proliferation and tumor maintenance, as well as to test the
      molecular mechanisms of tumor resistance to pathway-targeted therapy.

PMID- 15970712
TI  - Killing of chromium-damaged cells by mismatch repair and its relevance to
      carcinogenesis.
AB  - Hexavalent chromium compounds are widespread environmental contaminants that are
      well recognized as human carcinogens and potent respiratory toxicants.
      Intracellular metabolism of chromium(VI) leads to the production of numerous
      chromium-DNA adducts that are primarily formed at the phosphate groups. The
      mechanism of toxicity of these DNA modifications in human cells has been
      uncertain for a long time because chromium and other phosphate-based adducts did
      not block DNA replication with purified polymerases. Our recent studies
      identified mismatch repair proteins as activators of toxic responses to chromium
      DNA damage, which resolved an apparent discrepancy in genotoxic activity of
      chromium adducts in cells and in vitro. The discovered mechanism of toxicity
      provided the basis for a novel model of chromium carcinogenesis based on the
      selection of resistant clones that lack mismatch repair and progress to cancer
      due to high levels of spontaneous mutagenesis.

PMID- 15970713
TI  - Venous and arterial thrombosis following administration of intravenous
      immunoglobulins.
AB  - Thrombotic events are an increasingly recognized complication of treatment with
      intravenous immunoglobulins (IVIg). We aimed to define clinical characteristics,
      risk factors and outcome for venous thrombosis as opposed to arterial thrombosis
      following administration of IVIg. Six patients with post-IVIg venous thrombosis
      were identified at our institution. In addition, a review of the literature
      revealed 65 reported cases. Arterial thrombosis (stroke and myocardial
      infarction) was four times more common than venous thrombosis (deep vein
      thrombosis and pulmonary embolism). The incidence rate was estimated at 0.15-1.2%
      per treatment course, but the large increase in reported cases in 2003 suggests
      that the true incidence may be significantly greater. The following differences
      were found between arterial and venous events: arterial thrombosis occurred early
      after IVIg administration (49% within 4 h, 77% within 24 h) and was associated
      with advanced age and atherosclerotic vascular disease; venous thrombosis
      occurred later (54% more than 24 h after IVIg administration) and was associated
      with factors contributing to venous stasis (obesity and immobility). Thirteen
      patients died (mortality 20%), 11 of whom had arterial thrombosis. In conclusion,
      IVIg-associated thrombosis is more common than previously recognized, and is
      associated with significant mortality. The different characteristics of arterial
      and venous events may reflect different pathophysiological mechanisms. A better
      understanding of these mechanisms should aid in defining a risk-benefit ratio for
      the individual patient.

PMID- 15970714
TI  - Antithrombin efficiency is maintained in vitro in human plasma following dilution
      with hydroxyethyl starches.
AB  - Hemodilution has been associated with changes in hemostasis secondary to
      modulation of procoagulant activity. However, direct effects of specific fluids
      on anticoagulants, such as antithrombin (AT), remained undefined. Thus, the
      purpose of this investigation was to determine whether hemodilution with
      hydroxyethyl starches (HES) directly diminishes plasma AT activity, which would
      be manifested by decreases in clot initiation time (reaction time, R) with
      thrombelastography greater than that seen with 0.9% NaCl (NS). Normal plasma and
      AT-deficient (<1% activity) plasma were diluted 0 or 30% with NS, Hextend (6%
      HES; average molecular weight, 450 kDa), PentaLyte (6% HES; average molecular
      weight, 220 kDa), or Voluven (6% HES; average molecular weight, 130 kDa) (n=6-7
      experiments per condition). Undiluted, normal plasma had an R value of 796+/-65
      s, which was significantly (P<0.05) greater than R values following NS (690+/-50
      s) or Voluven (675+/-68 s) dilution. R values of normal plasma diluted with
      Hextend (831+/-51 s) or PentaLyte (801+/-72 s) were not different from undiluted
      plasma but were significantly (P<0.05) greater than those observed following NS
      or Voluven dilution. There were no significant differences between the conditions
      when AT-deficient plasma was utilized (R range, 404-440 s). Rather than interfere
      with AT activity, HES with an average molecular weight of 220-450 kDa maintain AT
      efficiency.

PMID- 15970715
TI  - The effects of high-dose heparin on inflammatory and coagulation parameters
      following cardiopulmonary bypass.
AB  - Systemic inflammation and the activation of the coagulation system following
      cardiopulmonary bypass (CPB) may contribute to postoperative complications. In
      vitro studies have demonstrated that heparin possesses anti-inflammatory
      properties. To ascertain the relative benefits of high versus low heparin doses,
      we studied the impact of varying heparin doses on the inflammatory response and
      coagulation system during and following CPB. Forty patients scheduled for
      elective coronary artery bypass surgery requiring CPB were randomized to either a
      low dose (300 U/kg) (Group L) or a high dose of unfractionated heparin (600 U/kg)
      (Group H). To evaluate the inflammatory response, proinflammatory cytokines
      [tumor necrosis factor-alpha and interleukin-6 (IL-6)] were measured at four
      different times: before CPB (T0), 30 min after the institution of CPB (T1), 30
      min after cross-clamp release (T2), and 4 h after the end of CPB (T3). Thrombin
      antithrombin complex, platelet factor 4 and anti-activated factor X heparin
      concentrations were also measured. Patients in Group H received greater heparin
      (44.934 U versus 27.741 U, P<0.001) and protamine (P=0.003) doses. Postoperative
      blood loss and blood products transfusions were not significantly different in
      the groups. At T1, mean heparin plasma concentration was higher in Group H
      (P<0.001). IL-6 was significantly lower in Group H compared with Group L (P=0.01)
      only at T1. Using a mixed-effects statistical model, tumor necrosis factor-alpha
      and IL-6 levels were comparable regardless of the heparin dose. Thrombin
      antithrombin complex levels were lower in Group H (P=0.04) and platelet factor 4
      levels were significantly lower in Group H at T2 (P=0.04). Higher heparin doses
      were associated with higher heparin concentrations during CPB. A high heparin
      dose achieved a better preservation of the coagulation system with less thrombin
      formation and platelet activation. The heparin dose had small influence on
      proinflammatory cytokines release.

PMID- 15970716
TI  - Haemostatic abnormalities in liver disease: could some haemostatic tests be
      useful as liver function tests?
AB  - The liver plays a central role in haemostasis, being the site of synthesis of
      most of the clotting factors, coagulation inhibitors and fibrinolytic parameters,
      in addition to its clearance of activated clotting and fibrinolytic factors.
      Nonetheless, no haemostatic test(s) is included among the routine liver function
      tests and this study aims to probe this possibility. The liver disease group
      (n=258) included acute hepatitis (n=25), chronic viral hepatitis (n=128),
      hepatitis B (HB) carriers (n=25), liver cirrhosis (n=67), and hepatocellular
      carcinoma (HCC) (n=13). The prothrombin time was significantly prolonged in acute
      hepatitis, liver cirrhosis and HCC. However, the reptilase time was prolonged in
      all the groups except in HB carriers, while the thrombin time was prolonged only
      in the HCC group. Antithrombin III and protein C levels exhibited significant
      reduction in acute hepatitis, liver cirrhosis and HCC. On the other hand, protein
      S levels (total and free) were reduced significantly in all the patients groups,
      including HB carriers when compared with healthy controls. Derangement of
      haemostatic tests is a common feature in liver disease, being most significant in
      acute hepatitis, liver cirrhosis and hepatocellular carcinoma. The most sensitive
      markers of hepatocyte malfunction are protein S (total and free) and the
      reptilase time as they were abnormal, in the mildest liver affections, when other
      biochemical tests as well as other haemostatic tests were normal. Further studies
      are needed to see whether these two tests qualify for inclusion among the routine
      liver function tests.

PMID- 15970717
TI  - The influence of acetylsalicylic acid intake by healthy volunteers on duplicate
      PFA-100 measurements.
AB  - The PFA-100 device is increasingly used for assessing platelet function. Its use
      to monitor anti-platelet therapy, like acetylsalicylic acid (ASA), has been
      described. In most studies single PFA-100 measurements were used. In this study,
      we evaluate the influence of ASA on duplicate measurements using
      collagen/epinephrine cartridges. Twelve healthy volunteers received a single dose
      of 160 mg ASA and 12 other healthy volunteers received 30 mg ASA during 10 days
      followed by 80 mg ASA during 10 days. PFA-100 measurements were performed in
      duplicate 1 and 24 h after the final intake of medication. The mean coefficient
      of variation of duplicate measurements before medication was 8.4% and at least
      two times higher after the intake of a single dose of 160 mg ASA or 30 mg ASA
      during 10 days. Per individual, huge differences between duplicate measurements
      were observed after ASA ingestion. Differences were less pronounced after
      ingestion of 80 mg ASA during 10 days, because six of 12 volunteers had a maximum
      PFA-100 value>300 s in both measurements. As a consequence, one should be
      cautious to use the PFA-100 to monitor ASA therapy in individual patients.

PMID- 15970718
TI  - Fever in pulmonary embolism.
AB  - This study was planned to investigate the characteristics of clinical and
      laboratory findings of patients with fever diagnosed as pulmonary embolism (PE)
      in comparison with PE patients without fever and patients with community-acquired
      pneumonia (CAP). Thirty-nine PE patients with fever without other identifiable
      causes (18 received antibiotics and 21 did not receive antibiotics) (study
      groups) were included in the study. 22 patients with PE without fever and 21
      patients diagnosed with CAP were retrospectively selected as control groups.
      Daily peak body temperature, risk factors for PE, symptoms, and physical and
      laboratory findings at admission were recorded. Patients with CAP demonstrated
      higher body temperature than PE patients with fever (38.5+/-0.6 versus 37.8+/-0.6
      degrees C, P=0.0001). Fever patterns were similar between the three groups of
      patients who had fever. The leukocyte count and the erythrocyte sedimentation
      rate (ESR) were slightly higher in the group of PE with fever versus PE without
      fever (11,465.6+/-4229.4/mm, 51.1+/-34.7/mm/h versus 10,777.3+/-4927.6/mm, 35.2+/
      30.1/mm/h, respectively) (P>0.05). The group of CAP showed significantly highest
      values of leukocyte count and ESR (15,490.5+/-5606.3/mm, 69.1+/-35.9/mm per h,
      respectively) (P<0.05). This study suggested that fever might accompany with PE.
      The presence of slight leukocytosis and increased ESR may not securely
      differentiate PE patients with fever from patients with CAP.

PMID- 15970719
TI  - No alteration in the PFA-100 in vitro bleeding time induced by the Ginkgo biloba
      special extract, EGb 761, in elderly patients with mild cognitive impairment.
AB  - EGb 761 is widely used in the management of mild cognitive impairment in the
      elderly population. Elucidation of the effects of EGb 761 on primary haemostasis
      via PFA-100 could represent an important step for better understanding of the
      haemostatic safety of EGb 761. The purpose of this prospective study is to assess
      the effects of Ginkgo biloba special extract, EGb 761, on PFA-100 in vitro
      bleeding time in elderly patients with mild cognitive impairment. A total of 40
      elderly patients aged 65-79 years who were referred for geriatric assessment and
      who were diagnosed as having mild cognitive impairment were included. Patients
      were started on 80 mg EGb-761 three times daily. The complete set of PFA-100 in
      vitro bleeding time and coagulation parameters including prothrombin time,
      activated partial thromboplastin time and International Normalized Ratio were
      assessed before and on the seventh day of treatment with EGb 761. There was no
      statistically significant prolongation in PFA-100 in vitro bleeding time or
      coagulation parameters in patients receiving EGb 761 after 7 days. The data about
      the safety of EGb 761 from the point of primary haemostasis in our elderly
      patient population with mild cognitive impairment casts hope for the future
      management of this 'difficult-to-treat' population with the promising Ginkgo
      extracts.

PMID- 15970720
TI  - Rheological analyses of coagulation of blood from different individuals with
      special reference to procoagulant activity of erythrocytes.
AB  - In our previous papers, we reported that factor IX (FIX), when activated by
      erythrocyte membranes, causes coagulation. We have identified and characterized
      the FIX-activating enzyme located in normal human erythrocyte membranes. In this
      paper, to examine physiological and pathological significances of procoagulant
      activity of erythrocytes, coagulation of blood obtained from different
      individuals was analyzed by means of a rheological technique. In more than 65% of
      subjects including normals and patients, the initiation of coagulation seemed to
      be governed by erythrocytes. Coagulation of whole blood and platelet-free plasma
      supplemented with erythrocytes had a tendency to occur rapidly in the elderly. It
      was suggested that the concentration of FIX-activating enzyme on erythrocyte
      membranes for aged donors was somewhat higher than that for young ages.
      Propagation reactions on erythrocyte membranes (i.e. factor X activation leading
      to thrombin generation after FIX activation) was slower than that on platelet
      membranes. Moreover, the propagation reaction on erythrocyte membranes was
      greatly dependent on individuals, whereas that on platelet membranes was not so
      much. Our study demonstrates that the activation of FIX by erythrocytes and
      subsequent propagation reaction on platelet membranes may be important for
      initiating and controlling blood coagulation reactions.

PMID- 15970721
TI  - Factor XII auto-antibodies present in a patient with a B-cell lymphoma.
AB  - A 64-year-old woman was transferred for investigation of a mediastinal mass,
      biopsy of which showed a diffuse large B-cell lymphoma. She was also found to
      have an antiphospholipid antibody. The pre-operative coagulation screen showed a
      prolonged activated partial thromboplastin time, 71.3 s (normal range, 26-36 s),
      which was not corrected by the addition of normal plasma. The dilute Russell's
      viper venom time was positive. Anti-cardiolipin assay was strongly positive,
      immunoglobulin M was 153 AU; immunoglobulin G was normal, 3.1 AU. Assays of
      factors VIII, IX and XI showed higher concentrations with increasing dilutions in
      one-stage factor assays from 1: 10 to 1: 80 suggestive of an inhibitor. Factor
      XII was 9 U/dl and results were unaffected by increasing dilution, suggesting
      specific antibodies to factor XII. The factor XII antigen was 40 U/dl. The
      patient had immunoglobulin M auto-antibodies to factor XII.

PMID- 15970722
TI  - Of four mutations in the factor VII gene in Tunisian patients, one novel mutation
      (Ser339Phe) in three unrelated families abrogates factor X activation.
AB  - Hereditary factor VII (FVII) deficiency is a rare bleeding disorder.
      Dysfunctional FVII variants characterized by normal or reduced levels of FVII
      antigen and discordantly low FVII activity have been described. In this study,
      seven unrelated Tunisian patients with FVII deficiency were examined. Molecular
      analysis revealed that three probands harbored a novel Ser339Phe mutation, one
      proband was inferred to have a novel splice site mutation in intron 2, c.226-2
      A>G and three probands had two previously described mutations, Arg304Gln and
      Cys310Phe. Expression of Ser339Phe in baby hamster kidney cells yielded secretion
      of FVII antigen at a concentration of 225+/-50 ng/ml, compared with 181+/-47
      ng/ml in cells transfected with wild-type FVII but with no demonstrable FVII
      activity. FVII Ser339Phe bound to tissue factor similarly to the binding of
      commercial recombinant activated FVII or recombinant wild-type FVII and was
      normally activated by activated factor X. The major defect of FVII Ser339Phe was
      its inability to activate factor X in the presence of tissue factor. Modeling
      predicted that the substitution of Ser339 by Phe abrogated substrate docking.

PMID- 15970724
TI  - Influence of two different buffered sodium citrate concentrations on coagulation
      testing.

PMID- 15970723
TI  - Increased procoagulant phospholipid activity in blood from patients with
      suspected acute coronary syndromes: a pilot study.
AB  - Increased platelet activation is well documented in patients with acute coronary
      syndromes and can be detected by various methods, including flow cytometry and
      enzyme-linked immunosorbent assay. However, such techniques require several steps
      and cannot provide quick results. Platelet activation ultimately results in
      procoagulant phospholipid exposure and we have previously described a simple
      activated factor X-activated clotting time (XACT) test that is insensitive to
      resting platelets but that is significantly shortened by activated platelets,
      microparticles and procoagulant phospholipids. Our aim was to determine whether
      the XACT test could be used to distinguish patients with chest pain due to
      cardiac ischaemia from those having chest pain due to non-cardiac causes. We thus
      carried out XACT tests on ethylenediamine tetraacetic acid whole blood and plasma
      samples obtained from 46 patients presenting to the emergency department with
      chest pain and from 30 controls. Sixteen cases (30%) were subsequently diagnosed
      as acute coronary syndromes. Blood samples from these patients displayed overall
      significantly shortened XACT results relative to both healthy controls (P<0.001)
      and chest pain not due to cardiac ischaemia (P<0.004). This discrimination was
      much better with whole blood samples than when platelet-poor plasmas were tested
      (P=0.153), suggesting that free microparticles were not the only factors
      responsible. Thus, the detection of increased procoagulant phospholipid activity
      in whole blood by shortened XACT results may be a simple and rapid diagnostic
      marker of some cardiac ischaemic events.

PMID- 15970725
TI  - Successful treatment of massive acute upper gastrointestinal bleeding in liver
      failure with activated recombinant factor VII (NovoSeven): a case report.

PMID- 15970726
TI  - Brain-behavior relations during motor processing in chronic tic and habit
      disorder.
AB  - OBJECTIVE: This study examined electrophysiological indices of preparation
      (readiness potential, RP) and execution (movement-associated potential, MAP)
      during automated and controlled reaction time (RT) in 13 chronic tic disorder, 17
      habit disorder, and 14 control participants. BACKGROUND: Both tic and habit
      disorders are hypothesized to involve states of heightened activation, which
      could impede initiation and the control of complex motor actions. METHOD: The
      electrophysiological signal was recorded from 4 electrodes (Fz, C3, C4, Pz)
      during a fixed 4-second foreperiod reaction time task. RESULTS: During automated
      responses, controls showed a shorter RP peak onset, and during controlled
      responses a longer MAP peak onset, compared with both clinical groups. The
      controls were the only group who showed a consistent linear relationship between
      RP and RT. CONCLUSIONS: Patients with chronic tic as well as habit disorder may
      not modulate cortical activation optimally in planning and executing both
      automated and controlled responses.

PMID- 15970727
TI  - Relationship of leukoaraiosis to cognitive decline and cognitive aging.
AB  - OBJECTIVE: Leukoaraiosis (LA) is a common finding on MRI scans of the elderly.
      However, its exact relationship to cognitive decline and dementia is in dispute.
      Because LA involves the paracallosal white matter, we sought to determine if LA,
      uncomplicated by ischemic lesions or complaints of cognitive impairment, is
      associated with cognitive loss or difficulties with interhemispheric integration
      of behavioral functions. METHODS: Two hundred fifty-seven MRI scans with deep
      white matter changes were screened. After a chart review, 38 patients had
      uncomplicated LA, and 31 gave informed consent to undergo cognitive and
      behavioral testing. RESULTS: LA severity was not related to any of the cognitive
      or behavioral assessments. However, some dependent measures showed medium effect
      sizes that were in keeping with published findings, indicating that LA has a
      marginal impact on cognition. In comparison, robust relationships with age were
      found for certain tasks, suggesting that our cohort size was sufficient to detect
      meaningful clinical relationships. CONCLUSION: Based on statistical
      interpretations using effect sizes, LA severity may be better viewed as a
      biomarker for physiological brain aging that is in advance of chronological age,
      leaving the elderly individual at greater risk for developing dementia.

PMID- 15970728
TI  - Lethal obesity associated with sodium valproate in a brain-injured patient.
AB  - A 34-year-old man developed posttraumatic epilepsy and a disinhibited
      orbitofrontal syndrome following severe head trauma at age 22. After an 11-year
      prison term marked by repeated impulsive aggression, he was transferred to a
      state psychiatric hospital. Replacement of phenytoin by valproic acid resulted in
      a 100-lb weight gain, exacerbation of sleep apnea, and right heart failure.
      Despite replacement of valproate with topiramate, he died of a cardiorespiratory
      arrest during a seizure. This case illustrates the potential risks associated
      with valproate therapy in the obese brain-damaged population.

PMID- 15970729
TI  - White matter volume and cognitive dysfunction in early Huntington's disease.
AB  - BACKGROUND: Structural abnormalities of the striatum and cognitive impairments
      have consistently been shown in patients with Huntington's disease (HD). Fewer
      studies have examined other cerebral structures in early HD and potential
      associations with cognition. METHOD: Ten patients with early HD and 10 matched
      control subjects underwent magnetic resonance imaging to provide quantitative
      measures (volumes) of cortical gray and white matter and the caudate, putamen,
      and thalamus. Patients completed the Unified Huntington's Disease Rating Scale,
      including three cognitive tasks. RESULTS: Although striatal volumes were clearly
      reduced, white matter was also morphologically abnormal. Cortical gray matter
      volume was not significantly correlated with cognitive performance. However, the
      cognitive tasks were most highly correlated with cerebral white matter and, to a
      lesser degree, striatal volume. CONCLUSIONS: Cerebral white matter volume may be
      an important variable to examine in future studies of HD.

PMID- 15970730
TI  - Cognitive impairment in acute cocaine withdrawal.
AB  - To perform a pilot study to examine a range of cognitive flexibility tasks early
      in cocaine withdrawal. BACKGROUND: Previous neuropsychological investigations of
      cocaine withdrawal have conflicted regarding whether impaired cognitive
      flexibility occurs. However, most studies have examined patients later in
      withdrawal. Anxiety and yohimbine-induced panic are greatest early in withdrawal,
      and both anxiety and increased noradrenergic tone can impair cognitive
      flexibility. METHOD: Twelve patients acutely withdrawing from cocaine were
      compared with gender-, age-, and estimated premorbid intelligence-matched control
      subjects on tests of cognitive flexibility as well as verbal fluency, verbal
      memory, spatial memory, and attention. RESULTS: As predicted, impairments were
      found on the cognitive flexibility tasks. Impairments also were present in verbal
      fluency and verbal memory but not spatial memory or attention. CONCLUSIONS: We
      propose that the cognitive flexibility impairment may relate to the increased
      noradrenergic activation recently described in cocaine withdrawal. Impairments on
      verbal tasks may also relate to an impaired flexibility in the search of semantic
      networks. Further research will explore the effects of pharmacologic manipulation
      of the noradrenergic system on cognition in acute withdrawal. Recently,
      propranolol has been shown to benefit patients in cocaine withdrawal. Further
      research will explore whether impaired cognitive flexibility related to altered
      noradrenergic tone could serve as a mechanism for this treatment response.

PMID- 15970731
TI  - Is schizophrenia associated with narcolepsy?
AB  - OBJECTIVE: To determine the nature of the relationship between schizophrenia-like
      psychosis and narcolepsy. BACKGROUND: A relationship between schizophrenia and
      narcolepsy has long been postulated due to the association of schizophrenia-like
      psychosis with narcolepsy and its treatment. METHOD: We report two patients who
      presented with schizophrenia-like psychosis of narcolepsy and review the
      literature regarding possible shared neurobiology between the two disorders that
      might explain their co-occurrence. RESULTS: There appears to be little in the way
      of common pathology between these two conditions when symptoms, human leukocyte
      antigen associations, rapid eye movement sleep architecture, D2-dopamine receptor
      changes, and hypocretinergic function are examined. CONCLUSIONS: The available
      literature suggests that schizophrenia-like psychosis in narcolepsy is most
      commonly medication related or a chance co-occurrence, with limited evidence for
      a separate psychosis of narcolepsy.

PMID- 15970732
TI  - An increased precision comparison of TMS-induced motor cortex BOLD fMRI response
      for image-guided versus function-guided coil placement.
AB  - OBJECTIVE: To examine with high precision the differences between function-guided
      and image-guided transcranial magnetic stimulation (TMS). METHOD: Using a
      calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic
      resonance imaging (fMRI), and individualized anatomy-based regional
      normalization, we conducted a two-phase study of TMS coil positioning guided by
      either function (elicited thumb motion) or image-based targeting of the "hand
      knob," the anatomy associated with fMRI activation during thumb motion. RESULTS:
      In every case, image-guided TMS coil placement produced a thumb movement response
      at thresholds similar to those found under function guidance. Unexpectedly,
      function-guided coil locations clustered bimodally over central and precentral
      sulci. Image-guided locations clustered as anticipated toward the targeted gyral
      crown. Despite these differences, blood oxygenation level-dependent (BOLD)
      activation locations and magnitude for the two methods displayed no consistent
      differences in mean or variance between or within subjects. Image guidance
      produced more consistent coil placement from subject to subject relative to
      targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments
      showed significantly slower return to baseline after TMS than was observed under
      function guidance. CONCLUSIONS: The results demonstrate the effectiveness and
      precision of image-guided positioning of TMS coils combined with a precisely
      adjustable holder/positioner and regional normalization. Image guidance provides
      an accurate TMS placement relative to individual anatomy when no external sign is
      available.

PMID- 15970733
TI  - Affective outcome following carbon monoxide poisoning: a prospective longitudinal
      study.
AB  - OBJECTIVE: To longitudinally assess the prevalence of depression and anxiety
      following carbon monoxide (CO) poisoning and to assess the contributions of mode
      of poisoning (accidental versus suicide attempt), cognitive sequelae, and oxygen
      dose (hyperbaric oxygen versus normobaric oxygen) to depression and anxiety.
      BACKGROUND: CO is the most common cause of poisoning in the United States and may
      result in neuropathologic changes and cognitive and neurologic sequelae, yet
      little is known regarding affective outcomes. METHOD: We prospectively assessed
      affect in 127 CO-poisoned patients. Self-report inventories of depression and
      anxiety were administered at 6 weeks and at 6 and 12 months post CO poisoning.
      The primary outcome was prevalence of depression and anxiety at 6 weeks. To
      determine the effect of mode of poisoning, cognitive sequelae, and oxygen dose,
      odds ratio estimates were calculated at all three times using logistic
      regression. RESULTS: Depression and anxiety were present in 45% of patients at 6
      weeks, 44% at 6 months, and 43% at 12 months. Patients with suicide attempt and
      cognitive sequelae had higher prevalence of depression and anxiety at 6 weeks. At
      12 months, there were no differences in depression or anxiety regardless of mode
      of poisoning, presence of cognitive sequelae, or oxygen dose. CONCLUSIONS: CO
      poisoning results in significant depression and anxiety that persist to at least
      12 months. Patients with cognitive sequelae and suicide attempt had a higher rate
      of depression and anxiety at 6 weeks but not at 12 months. Clinicians need to be
      aware of affective morbidity following CO poisoning and remain vigilant about CO
      prevention.

PMID- 15970734
TI  - Audiovisual peduncular hallucinations: a release of cross-modal integration
      sites?
AB  - We report the case of a patient with multiple sclerosis with congruent visual and
      auditory hallucinations of deceased familiar persons that lasted continuously for
      several days. Magnetic resonance imaging revealed an isolated, predominantly left
      sided lesion in the periaqueductal segment of the mesencephalon. We propose that
      these hallucinations represent a bimodal variant of classic peduncular
      hallucinations, brought about by a deregulation of modulatory superior collicular
      activity and a release of cross-modal integrative functions of the superior
      temporal sulcus.

PMID- 15970736
TI  - Pseudoneglect in solid-line versus character-line bisection tasks: a test for
      attention dominance theory.

PMID- 15970739
TI  - Regional anesthesia group practice in the university hospital setting and
      ambulatory/regional anesthesia clinical pathway formulation.

PMID- 15970740
TI  - Regional anesthesia group practice in multihospital private practice settings and
      in orthopedic specialty hospitals.

PMID- 15970741
TI  - Regional anesthesia group practice in pediatric outpatients: my experiences in
      France and Quebec.

PMID- 15970742
TI  - Billing for outpatient regional anesthesia services in the United States.

PMID- 15970743
TI  - Hospital facilities and resource management: economic impact of a high-volume
      regional anesthesia program for outpatients.

PMID- 15970744
TI  - Nerve block induction rooms--physical plant setup, monitoring equipment, block
      cart, and resuscitation cart.

PMID- 15970745
TI  - Role of ultrasound in startup regional anesthesia practice for outpatients.

PMID- 15970746
TI  - Management of peripheral nerve block catheters at home.

PMID- 15970747
TI  - Outcomes after regional anesthesia.

PMID- 15970748
TI  - Complications associated with peripheral nerve blocks: lessons from the ASA
      closed claims project.

PMID- 15970749
TI  - Diagnosis and management of peripheral nerve block complications.

PMID- 15970750
TI  - Neuraxial techniques for ambulatory anesthesia.

PMID- 15970751
TI  - Outpatient regional anesthesia for foot and ankle surgery.

PMID- 15970752
TI  - Regional anesthesia procedures for ambulatory knee surgery: effects on in
      hospital outcomes.

PMID- 15970753
TI  - Minimally invasive total hip replacement as an ambulatory procedure.

PMID- 15970754
TI  - Regional anesthesia procedures for outpatient shoulder surgery.

PMID- 15970755
TI  - Outpatient regional anesthesia for upper extremity surgery.

PMID- 15970756
TI  - Outcomes after paravertebral blocks.

PMID- 15970757
TI  - Multimodal analgesia techniques for ambulatory surgery.

PMID- 15970758
TI  - Antiemetics in outpatient regional anesthesia for invasive orthopedic surgery.

PMID- 15970762
TI  - Selective botulinum neurotoxin application: the interaction of evolution,
      biology, and culture in diagnosing and healing the miscues of human facial
      expression.

PMID- 15970763
TI  - Social implications of hyperdynamic facial lines and patient satisfaction
      outcomes.

PMID- 15970764
TI  - Pharmacology and immunology of botulinum neurotoxins.

PMID- 15970765
TI  - A review of facial anatomy as it relates to the use of botulinum toxin.

PMID- 15970766
TI  - Benign essential blepharospasm.

PMID- 15970767
TI  - Advanced functional oculofacial indications of botulinum toxin.

PMID- 15970768
TI  - Botulinum toxin for headache.

PMID- 15970769
TI  - Practical aspects of cosmetic botulinum toxin.

PMID- 15970770
TI  - Cosmetic botulinum neurotoxin application.

PMID- 15970771
TI  - Modifying brow position with botulinum toxin.

PMID- 15970772
TI  - Botulinum toxin below the eyes.

PMID- 15970773
TI  - Adjunctive botulinum toxin type A: fillers and light-based therapies.

PMID- 15970774
TI  - The cosmetic use of botulinum toxin type B.

PMID- 15970775
TI  - Complications with the use of botulinum toxin.

PMID- 15970777
TI  - Time is money for both the healthy and the sick.

PMID- 15970778
TI  - Estimating patient time costs associated with colorectal cancer care.
AB  - BACKGROUND: Nonmedical costs of care, such as patient time associated with travel
      to, waiting for, and seeking medical care, are rarely measured systematically
      with population-based data. OBJECTIVES: The purpose of this study was to estimate
      patient time costs associated with colorectal cancer care. METHODS: We identified
      categories of key medical services for colorectal cancer care and then estimated
      patient time associated with each service category using data from national
      surveys. To estimate average service frequencies for each service category, we
      used a nested case control design and SEER-Medicare data. Estimates were
      calculated by phase of care for cases and controls, using data from 1995 to 1998.
      Average service frequencies were then combined with estimates of patient time for
      each category of service, and the value of patient time assigned. Net patient
      time costs were calculated for each service category, summarized by phase of
      care, and compared with previously reported net direct costs of colorectal cancer
      care. RESULTS: Net patient time costs for the 3 phases of colorectal cancer care
      averaged dollar 4592 (95% confidence interval [CI] dollar 4427-4757) over the 12
      months of the initial phase, dollar 2788 (95% CI dollar 2614-2963) over the 12
      months of the terminal phase, and dollar 25 (95% CI: dollar 23-26) per month in
      the continuing phase of care. Hospitalizations accounted for more than two thirds
      of these estimates. Patient time costs were 19.3% of direct medical costs in the
      initial phase, 15.8% in the continuing phase, and 36.8% in the terminal phase of
      care. CONCLUSIONS: Patient time costs are an important component of the costs of
      colorectal cancer care. Application of this method to other tumor sites and
      inclusion of other components of the costs of medical care will be important in
      delineating the economic burden of cancer in the United States.

PMID- 15970779
TI  - National estimates of the effects of mandatory Medicaid managed care programs on
      health care access and use, 1997-1999.
AB  - OBJECTIVE: We sought to explore how mandatory Medicaid managed care programs
      affect access to care and use among full-year Medicaid beneficiaries not
      receiving SSI or Medicare. RESEARCH DESIGN: We used data from the 1997 and 1999
      National Survey of America's Families. To establish what Medicaid beneficiaries'
      access and use would have been in the absence of Medicaid managed care (MMC) and
      to control for unobserved county differences, we estimated difference-in
      difference models using a comparison group of privately insured individuals who
      we would not expect to be affected by MMC. RESULTS: We found weaker effects of
      MMC programs for children than adults. The strongest result is that mandatory HMO
      programs lower the probability of Medicaid adults using emergency rooms, when
      implemented alone or in combination with Primary Care Case Management (PCCM)
      programs. PCCM programs reduced the number of visits among adults but had little
      effect on other measures of access and use. There was less preventive care in
      mandatory HMO counties for women, suggesting that the federally required external
      quality review may be appropriate. CONCLUSION: The effects of Medicaid managed
      care vary with the type of program, and policy makers should not expect programs
      that rely on PCCMs to have the same effects as those that incorporate mandatory
      HMO enrollment. Moreover, none of the program models had strong and consistent
      effects across the indicators of access and use that we considered.

PMID- 15970780
TI  - Should Do-Not-Resuscitate status be included as a mortality risk adjustor? The
      impact of DNR variations on performance reporting.
AB  - BACKGROUND: The practice of ordering "Do-Not-Resuscitate" (DNR) varies across
      hospitals. No research has explored how the DNR variation would affect cross
      institutional performance reporting when DNR status is used as a risk adjustor.
      OBJECTIVE: We sought to assess the impact of DNR variation on performance
      reporting. RESEARCH DESIGN: We used retrospective clinical data abstracted from
      chart review for our analysis. SUBJECTS: We studied a total of 184,057 adult
      patients admitted to 149 Pennsylvania acute-care hospitals in 2001 for ischemic
      stroke, hemorrhagic stroke, pneumonia, acute myocardial infarction, congestive
      heart failure, and sepsis. MEASURES: DNR rate and DNR mortality rate per patient
      at the hospital level was assessed. DNR also was used as an additional covariate
      to predict mortality in logistic regression models. Change of rank and outlier
      status at the hospital level based on adjusted mortality determined by
      multivariable logistic models with or without DNR was used to assess the impact
      of DNR on performance reporting. RESULTS: Large variations in DNR rates (1-37%)
      and DNR mortality rates (8-60%) existed across hospitals. There was a significant
      negative correlation between DNR rates and DNR mortality rates (r = -0.66, P <
      0.0001). Adding DNR as a covariate resulted in a systematic shift in performance
      rank (r = 0.88, P < 0.0001) and change in statistical outlier-status (n = 33),
      which favored hospitals with higher DNR rates. CONCLUSION: Using locally defined
      DNR as an additional covariate potentially introduces systematic bias in
      performance reporting. A more uniform definition and application of DNR is needed
      if it is to be included as a risk adjustor.

PMID- 15970781
TI  - Does the collaborative model improve care for chronic heart failure?
AB  - BACKGROUND: Organizationally based, disease-targeted collaborative quality
      improvement efforts are widely applied but have not been subject to rigorous
      evaluation. We evaluated the effects of the Institute of Healthcare Improvement's
      Breakthrough Series (IHI BTS) on quality of care for chronic heart failure (CHF).
      RESEARCH DESIGN: We conducted a quasi-experiment in 4 organizations participating
      in the IHI BTS for CHF in 1999-2000 and 4 comparable control organizations. We
      reviewed a total of 489 medical records obtained from the sites and used a
      computerized data collection tool to measure performance on 23 predefined quality
      indicators. We then compared differences in indicator performance between the
      baseline and post-intervention periods for participating and non-participating
      organizations. RESULTS: Participating and control patients did not differ
      significantly with regard to measured clinical factors at baseline. After
      adjusting for age, gender, number of chronic conditions, and clustering by site,
      participating sites showed greater improvement than control sites for 11 of the
      21 indicators, including use of lipid-lowering and angiotensin converting enzyme
      inhibition therapy. When all indicators were combined into a single overall
      process score, participating sites improved more than controls (17% versus 1%, P
      < 0.0001). The improvement was greatest for measures of education and counseling
      (24% versus -1%, P < 0.0001). CONCLUSIONS: Organizational participation in a
      common disease-targeted collaborative provider interaction improved a wide range
      of processes of care for CHF, including both medical therapeutics and education
      and counseling. Our data support the use of programs like the IHI BTS in
      improving the processes of care for patients with chronic diseases.

PMID- 15970782
TI  - Risk perception and impact of Severe Acute Respiratory Syndrome (SARS) on work
      and personal lives of healthcare workers in Singapore: what can we learn?
AB  - INTRODUCTION: Healthcare workers (HCWs) were at the frontline during the battle
      against Severe Acute Respiratory Syndrome (SARS). Understanding their fears and
      anxieties may hold lessons for handling future outbreaks, including acts of
      bioterrorism. METHOD: We measured risk perception and impact on personal and work
      life of 15,025 HCWs from 9 major healthcare institutions during the SARS epidemic
      in Singapore using a self-administered questionnaire and Impact of Events Scale
      and analyzed the results with bivariate and multivariate statistics. RESULTS:
      From 10,511 valid questionnaires (70% response), we found that although the
      majority (76%) perceived a great personal risk of falling ill with SARS, they
      (69.5%) also accepted the risk as part of their job. Clinical staff (doctors and
      nurses), staff in daily contact with SARS patients, and staff from SARS-affected
      institutions expressed significantly higher levels of anxiety. More than half
      reported increased work stress (56%) and work load (53%). Many experienced social
      stigmatization (49%) and ostracism by family members (31%), but most (77%) felt
      appreciated by society. Most felt that the personal protective measures
      implemented were effective (96%) and that the institutional policies and
      protocols were clear (93%) and timely (90%). CONCLUSION: During epidemics,
      healthcare institutions have a duty to protect HCWs and help them cope with their
      personal fears and the very stressful work situation. Singapore's experience
      shows that simple protective measures based on sound epidemiological principles,
      when implemented in a timely manner, go a long way to reassure HCWs.

PMID- 15970783
TI  - Moving to mandatory Medicaid managed care in Ohio: impacts on pregnant women and
      infants.
AB  - BACKGROUND: Understanding the impacts of Medicaid managed care on pregnant women
      is critical because Medicaid covers more than a third of all births nationally,
      many under managed care arrangements. OBJECTIVES: We sought to examine the
      impacts of mandatory Health Maintenance Organization (HMO) enrollment on prenatal
      care use, smoking, and birth weight for Medicaid-covered pregnant women in Ohio.
      RESEARCH DESIGN: Impact estimates are derived from a pre-post design with a
      comparison group, using Ohio birth certificate data linked to Medicaid enrollment
      files. Between April 1993 and April 1995 is the baseline period and October 1997
      to June 1998 is the post-period. The treatment group consists of deliveries in 6
      counties that implemented mandatory HMO enrollment in the mid 1990s; the
      comparison group consists of deliveries in 4 counties with voluntary HMO
      enrollment. SUBJECTS: Medicaid-covered deliveries to 24,799 non-Hispanic white
      women with no college education living in Ohio. MEASURES: Seven outcomes are
      analyzed: first trimester care; last trimester or no care; adequate prenatal
      care; inadequate prenatal care; smoking during pregnancy; and birth weight.
      RESULTS: Our findings indicate that mandatory HMO enrollment in Ohio's Medicaid
      program had positive effects on prenatal care and led to reductions in maternal
      smoking. No effects were found on birth weight. CONCLUSIONS: Even with the
      improvements related to Medicaid managed care, rates of inadequate prenatal care
      and maternal smoking remain relatively high. Addressing the underlying risk
      factors that are facing poor women and further expanding public programs may be
      critical to achieving further progress.

PMID- 15970784
TI  - Validity of using an electronic medical record for assessing quality of care in
      an outpatient setting.
AB  - OBJECTIVE: We sought to evaluate the validity of retrieving data from a
      commercial, outpatient electronic medical record (EMR) to assess the management
      of pharyngitis, an important measure of quality of healthcare in pediatrics and a
      new measure for the Health Plan Employer Data and Information Set (HEDIS).
      METHODS: For children ages 3-18 years, we electronically identified clinical
      encounters with diagnoses of pharyngitis using 3 different strategies (an EMR
      based strategy, an administrative data-based strategy, and a reference strategy
      which used medical record review). By each strategy, we calculated the proportion
      of episodes of pharyngitis during 1 year for which management of pharyngitis
      adhered to published guidelines. RESULTS: Among 479 total episodes of
      pharyngitis, 434 (91%) were from the EMR-based strategy and 281 (59%) from the
      administrative data-based strategy. Review of the records (the reference
      strategy) found that 391 of 479 (82%) were confirmed episodes of pharyngitis. A
      diagnostic test for group A streptococcus (GAS) was performed at 310 of 434 (71%)
      of episodes identified by the EMR-based strategy and at 214 of 281 (76%) of
      episodes by the administrative data-based strategy (P = 0.045). By the reference
      strategy, a diagnostic test was done in 301 of 391 (77%); more than at episodes
      found by the EMR-based strategy (71%, P < 0.001). CONCLUSIONS: The EMR-based
      strategy resulted in a statistically different proportion of episodes having
      diagnostic testing for GAS compared with a reference strategy. Complete
      evaluations to validate strategies for extracting data from electronic databases
      are necessary before assuming that measures of quality of care will be the same
      regardless of the source of data.

PMID- 15970785
TI  - Evaluating the performance of medicare fee-for-service providers using the health
      outcomes survey: a comparison of two methods.
AB  - BACKGROUND: Health status measures are now being used for evaluating the
      performance of health care organizations. Trends in SF-36 component scores have
      previously been examined for Medicare-managed care plans but not for providers
      serving Medicare fee-for-service (FFS) beneficiaries. We compared 2 methods for
      evaluating the performance of Medicare FFS providers, the Research Triangle
      Institute (RTI) and Health Assessment Laboratory (HAL) methods. METHODS: Data
      were collected from 6547 Medicare FFS beneficiaries in 10 cohorts. SF-36 Physical
      Health (PCS) and Mental Health (MCS) component scores were computed at baseline
      and after a 2-year follow-up. The RTI approach predicts follow-up scores based on
      a standard care regression model. The HAL approach determines the percentage of
      beneficiaries whose status is the "same or better" at follow-up. Both approaches
      then compare observed to expected scores for each cohort. RESULTS: The HAL method
      did not detect any statistically significant differences for the PCS; the RTI
      method detected a small PCS difference for one cohort. The HAL method identified
      4 cohorts that had significantly higher MCS scores; the RTI approach identified
      one cohort with significantly lower scores. CONCLUSIONS: The 2 approaches
      provided consistent assessments of provider performance for the PCS but not for
      the MCS. The differences in the MCS results may have been affected by differing
      treatment of deaths during follow-up. The HAL approach disregards deaths for the
      MCS, whereas the RTI method imputes values for death. Implications of using self
      reported health status for monitoring provider performance are discussed.

PMID- 15970786
TI  - The added value of claims for cancer surveillance: results of varying case
      definitions.
AB  - OBJECTIVE: As cancer diagnosis and treatment has moved to the outpatient
      healthcare setting, traditional cancer surveillance tools are less effective for
      complete and unbiased capture of incident cases. This study evaluates the
      potential for Medicare data to supplement cancer surveillance in a unique manner
      by using a standard that is independent of a central cancer registry. DESIGN:
      State cancer registry records were matched with Medicare data. Case validation
      included inpatient record abstraction combined with a mail/telephone survey of
      treating physicians. The positive predictive value (PPV), sensitivity (capture
      rate), and potential additional cases were calculated for 6 Medicare claims-based
      case definitions. RESULTS: The PPV varied according to cancer site and
      definition, ranging from 70%-97% (prostate) to 87%-98% (breast). Sensitivity
      varied inversely with PPV, ranging from 51%-94% (breast) to 10%-88% (lung). The
      most important factors that predicted being missed by the registry were having no
      admission to an ACOS-certified hospital and no surgical treatment. CONCLUSION:
      Medicare data represent a valid resource for supplementing state cancer
      registries in surveillance efforts. This potential is especially applicable to
      cancers predominantly diagnosed and treated outside the hospital setting.

PMID- 15970787
TI  - Underreporting of computed tomography and magnetic resonance imaging procedures
      in inpatient claims data.
AB  - BACKGROUND: ICD-9-CM procedure codes in inpatient claims data are used for a wide
      range of purposes, such as monitoring utilization, costs, and quality, and
      adjusting for patient risk. However, many procedures may be underreported because
      they are not required for reimbursement via Diagnosis-Related Group (DRG)
      assignment (non-DRG procedures). OBJECTIVES: This study examined the extent and
      variability of ICD-9-CM procedure code reporting for 2 commonly employed non-DRG
      imaging procedures, computerized tomography (CT) and magnetic resonance imaging
      (MRI). RESEARCH DESIGN: Using nonfederal hospital inpatient claims (n = 56,091)
      from Washington State Inpatient Data for 1997, ICD-9-CM procedure and Universal
      Billing revenue codes for CT and MRI were compared by payer and hospital
      characteristics. RESULTS: When compared with revenue codes, ICD-9-CM procedure
      coding was found to be considerably underreported and variable, with only 33% of
      CT and 43% of MRI procedures being recorded. Moreover, the frequency of
      underreporting of both procedures did not appear to be random, with 31 of 72
      hospitals that reported revenue codes for the CT not recording any ICD-9-CM codes
      for the procedure. Of the 48 hospitals that reported revenue codes for the MRI,
      15 failed to record any ICD-9-CM codes that indicated its use. Statistically
      significant differences in median coding frequencies by teaching and rural status
      were found for both procedures, while ownership was an important factor in CT
      reporting variability. CONCLUSIONS: This nonrandom variability in reporting can
      potentially bias utilization studies as well as risk-adjustment outcome estimates
      of techniques that rely on reporting of these procedures (eg, APR-DRG and AHRQ
      CCS). An effort to define a universally agreed upon list of non-DRG procedures to
      be coded in all US hospitals would greatly improve the capacity of health
      services researchers to conduct important utilization, outcome and policy
      studies.

PMID- 15970788
TI  - Gaps in enrollment from a Medicaid managed care program: effects on emergency
      department visits and hospitalizations for children with asthma.
AB  - BACKGROUND: For high-risk children with asthma enrolled in Medicaid, loss of
      Medicaid coverage is a potential threat to access to quality asthma care.
      OBJECTIVE: We sought to quantify the effect of gaps in enrollment on emergency
      department visits and hospitalizations for children with asthma in TennCare,
      Tennessee's managed care program for Medicaid-eligible and uninsured children.
      METHODS: Children with asthma were identified from a research database of files
      maintained by the state. Gaps in enrollment in the state insurance program were
      measured between 1998 and 2002. Children with gaps were compared with children
      without gaps with respect to emergency department visits and hospitalizations for
      asthma, respiratory illnesses, croup, and other diagnoses. RESULTS: Among
      children who met study definitions of asthma, 2373 experienced a gap in
      enrollment during the study period (10.4%). The rate of hospitalizations and
      emergency department visits for children with gaps (7402/10,000 person years) was
      significantly lower than the rate of study events for children with no gaps
      (9230/10,000 person years) (adjusted incidence rate ratio 0.88; 95% confidence
      interval 0.81-0.96). The rate of hospitalizations for asthma and other
      respiratory conditions was not different between the 2 groups; however, there was
      a significantly lower rate of hospitalizations for other reasons for children
      with gaps (adjusted incidence rate ratio 0.59; 95% confidence interval 0.41
      0.86). CONCLUSIONS: Children with asthma who had gaps in a Medicaid managed care
      insurance program had no increase in asthma related emergency department visits
      and hospitalizations. Children who had gaps did have fewer nonrespiratory
      emergency department visits and hospitalizations than their non-gap counterparts.
      Further study is needed to explore the reasons for this unexpected finding.

PMID- 15970789
TI  - Predicting risk-adjusted mortality for CABG surgery: logistic versus hierarchical
      logistic models.
AB  - BACKGROUND: In recent years, several studies in the medical and health service
      research literature have advocated the use of hierarchical statistical models
      (multilevel models or random-effects models) to analyze data that are nested (eg,
      patients nested within hospitals). However, these models are computer-intensive
      and complicated to perform. There is virtually nothing in the literature that
      compares the results of standard logistic regression to those of hierarchical
      logistic models in predicting future provider performance. OBJECTIVE: We sought
      to compare the ability of standard logistic regression relative to hierarchical
      modeling in predicting risk-adjusted hospital mortality rates for coronary artery
      bypass graft (CABG) surgery in New York State. DESIGN, SETTING AND PATIENTS: New
      York State CABG Registry data from 1994 to 1999 were used to relate statistical
      predictions from a given year to hospital performance 2 years hence. MAIN OUTCOME
      MEASURES: Predicted and observed hospital mortality rates 2 years hence were
      compared using root mean square errors, the mean absolute difference, and the
      number of hospitals whose predicted mortality rate data was within a 95%
      confidence interval around the observed mortality rate. RESULTS: In these data,
      standard logistic regression performed similarly to hierarchical models, both
      with and without a second level covariate. Differences in the criteria used for
      comparison were minimal, and when the differences could be statistically tested
      no significant differences were identified. CONCLUSIONS: It is instructive to
      compare the predictive abilities of alternative statistical models in the process
      of assessing their relative performance on a specific database and application.

PMID- 15970790
TI  - A national catalog of preference-based scores for chronic conditions in the
      United States.
AB  - BACKGROUND: The variability in preferences used in quality-adjusted life-years
      estimation jeopardizes the comparability of cost-effectiveness analyses and has
      led the Panel on Cost-Effectiveness in Health and Medicine (the PCEHM) to call
      for a catalog of "off-the-shelf" preference weights associated with conditions
      that can be used by health researchers without the burden of collecting primary
      data. OBJECTIVE: The current research responds to the call by developing a
      nationally representative catalog of preference-based scores for chronic
      conditions and associated sociodemographic characteristics. METHODS: The authors
      report the EQ-5Dindex scores of chronic conditions and associated
      sociodemographic characteristics in the nationally representative Medical
      Expenditure Panel Survey (MEPS). Chronic conditions were coded using "quality
      priority conditions" (QPC) and clinical classification categories (CCC). OLS,
      Tobit, and censored least absolute deviations (CLAD) regression models were used
      to provide condition estimates adjusted for age, comorbidity, gender, race,
      ethnicity, income, and education. RESULTS: Unadjusted and adjusted EQ-5Dindex
      scores for each QPC and CCC code are presented. EQ-5Dindex scores for older age
      categories were lower than younger categories, female scores were lower than
      males, certain racial groups had lower scores than others, and EQ-5Dindex scores
      were higher for individuals with higher education and income levels. CONCLUSION:
      The preference-based chronic condition scores reported in this research are
      nationally representative and may be useful to researchers to calculate quality
      adjusted life-years for cost-effectiveness analyses and population-based burden
      of illness studies without the difficulty of primary data collection. Further
      research is necessary to validate these scores in condition-specific studies.

PMID- 15970791
TI  - The erbB2/HER2/neu receptor polymorphism Ile655Val and breast cancer risk.
AB  - The erbB2 (HER2/neu) gene is found amplified in tumours. A single nucleotide
      polymorphism at codon 655 (Ile655Val) has been studied in a number of case
      control studies with respect to breast cancer risk, with conflicting results. The
      aim of the present study was to examine the association between this polymorphism
      and breast cancer risk in a prospective, predominantly Caucasian cohort of women,
      the Nurses' Health Study. We genotyped the Ile655Val single nucleotide
      polymorphism (rs1801200) in 1271 incident breast cancer cases, and 1667 controls
      who were selected from the Nurses' Health Study blood cohort. Controls were
      matched to cases on age, menopausal status, fasting status and postmenopausal
      hormone use at blood draw. An inverse association was observed between the
      Val/Val genotype and breast cancer risk (Val/Val versus Ile/Ile odds ratio=0.68,
      95% confidence interval 0.47-0.98). We conclude that this polymorphism is not
      associated with an increase in breast cancer risk, and may in fact be associated
      with a modest decrease in risk.

PMID- 15970792
TI  - Significance of a common single nucleotide polymorphism in exon 10 of the
      follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH:
      a pharmacogenetic approach to controlled ovarian hyperstimulation.
AB  - The p.N680S sequence variation of the follicle-stimulating hormone (FSH) receptor
      gene was previously shown to influence the ovarian response to FSH in normo
      ovulatory women undergoing controlled ovarian hyperstimulation. In this
      prospective, randomized, controlled study, we tested whether the same daily dose
      of FSH results in lower levels of oestradiol in women homozygous for the p.N680S
      sequence variation, and whether the difference can be overcome by higher FSH
      doses. Women undergoing controlled ovarian hyperstimulation for in vitro
      fertilization or intracytoplasmic sperm injection and homozygous for the wild
      type or for the p.N680S FSH receptor were randomly assigned to group I (Ser/Ser,
      n=24), receiving an FSH dose of 150 U/day, or group II (Ser/Ser, n=25), receiving
      an FSH dose of 225 U/day. In group III (Asn/Asn, n=44), the FSH dose was 150
      U/day. Age and basal FSH levels were not different between groups. At ovulation
      induction, total FSH doses were comparable in group I (1631+/-96 U) and group III
      (1640+/-57 U) but significantly higher in group II (2421+/-112 U) (P<0.001). Peak
      oestradiol levels on the day of human chorionic gonadotrophin (hCG)
      administration were significantly lower in group I (5680+/-675 pmol/l) compared
      to group III (8679+/-804 pmol/l) (P=0.028). Increasing the FSH dose from 150 to
      225 U/day overcame the lower oestradiol response in women with Ser/Ser (group II,
      7804+/-983 pmol/l). In women undergoing controlled ovarian hyperstimulation, the
      p.N680S sequence variation results in lower oestradiol levels following FSH
      stimulation. This lower FSH receptor sensitivity can be overcome by higher FSH
      doses.

PMID- 15970793
TI  - A promoter polymorphism (-77T>C) of DNA repair gene XRCC1 is associated with risk
      of lung cancer in relation to tobacco smoking.
AB  - X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair
      proteins involved in the base-excision repair pathway. Functional Polymorphisms
      in the XRCC1 gene may lead to decreased DNA repair capacity and thus confer
      inherited predisposition to cancer risk. In this case-control study of 710
      patients with incident lung cancer and 710 cancer-free controls who were
      frequency matched on age, sex and residential area, we genotyped a novel T>C
      transition at the promoter region (-77T>C) of XRCC1 and other two common non
      synonymous polymorphisms (Arg194Trp and Arg399Gln) to determine their
      associations with risk of lung cancer. We found that compared with the -77TT wild
      type homozygote, the variant genotypes were associated with significantly
      increased risk of lung cancer [adjusted odds ratio (OR)=1.51; 95% confidence
      interval (CI)=1.17-1.94 for -77TC; OR=2.98; 95% CI=0.93-9.59 for -77CC; and
      OR=1.55; 95% CI=1.21-1.98 for -77TC/CC]. By contrast, no significant associations
      were observed between the other two exonic variants (Arg194Trp and Arg399Gln) and
      lung cancer risk. Furthermore, we observed a 9.82-fold increased risk (95%
      CI=5.66-17.02) for heavy smokers carrying the -77C variant (-77TC/CC) and a 4.07
      fold increased risk (95% CI=2.85-5.81) for heavy smokers not carrying the
      variant. However, the interaction between the -77T>C variant and cumulative
      smoking was not statistically significant (P=0.1560). These findings indicate
      that the new XRCC1 -77T>C polymorphism may contribute to the aetiology of lung
      cancer. Further functional studies are warranted to elucidate the underlying
      molecular mechanisms of the association.

PMID- 15970794
TI  - Common genetic polymorphisms in the 5'-flanking region of the SULT1A1 gene:
      haplotypes and their association with platelet enzymatic activity.
AB  - SULT1A1 is a phase II detoxification enzyme involved in the biotransformation of
      a wide variety of endogenous and exogenous phenolic compounds. Human platelet
      SULT1A1 enzymatic activity shows marked inter-individual variability and a common
      coding polymorphism, SULT1A1*1/*2, has been described that accounts for a
      proportion of this variability. We examined the 5'-flanking region of the SULT1A1
      gene to determine if genetic variability in this portion of the gene influenced
      enzymatic activity. Direct sequencing revealed five common genetic polymorphisms
      (-624G>C, -396G>A, -358A>C, -341C>G and -294T>C) that were present at different
      allele frequencies in Caucasian, African-American and Chinese groups. Platelet
      SULT1A1 enzymatic activity was significantly correlated with individual promoter
      region polymorphisms and the associations were different between African
      Americans and Caucasians. Haplotypes were constructed and platelet enzymatic
      activity according to haplotype was examined. The haplotypes were also
      significantly correlated with activity; haplotypes GAACT and GGACT (accounting
      for 13% and 5% of inter-individual variability in platelet activity,
      respectively) were important in Caucasians while haplotypes GAACC, GAACT and
      GGACC (accounting for 8%, 5% and 4% of variability) were significantly associated
      with activity in African-Americans. The coding region polymorphism, SULT1A1*1/*2
      was in linkage disequilibrium with the promoter region polymorphisms and showed
      no effect on activity when examined in the context of the 5'-flanking region
      polymorphisms. These studies indicate that variation in the promoter region of
      the SULT1A1 gene exerts a significant influence on enzymatic activity.

PMID- 15970795
TI  - In-vitro and in-vivo effects of the CYP2C9*11 polymorphism on warfarin metabolism
      and dose.
AB  - OBJECTIVE: To determine the in-vitro and in-vivo effects of the CYP2C9*11
      polymorphism on (S)-warfarin metabolism. METHODS AND RESULTS: The *11 allele that
      results in mutation of Arg335-->Trp occurred with a frequency of approximately 1%
      in Caucasian and African-American populations. Four subjects carrying the *1/*11
      genotype were identified in a clinical cohort of 192 warfarin patients. Compared
      to control subjects with the *1/*11 genotype (n=127), the *1/*11 group exhibited
      a 33% reduction in warfarin maintenance dose, that was independent of study
      population age or INR. In-vitro studies directed towards understanding the
      mechanism of reduced in-vivo activity revealed very low levels of holo-CYP2C9.11
      expression in insect cells and decreased solubility in the presence of detergent.
      Membrane preparations of CYP2C9.11 contained inactive P420 and exhibited a
      shorter half-life for thermally induced conversion of P450 to P420 than CYP2C9.1.
      Metabolic studies demonstrated that functional CYP2C9.11 possessed similar (S)
      warfarin hydroxylation regioselectivity and modestly reduced catalytic efficiency
      relative to the wild-type enzyme. CONCLUSIONS: In-vivo reduction in CYP2C9 (S)
      warfarin activity due to the CYP2C9*11 polymorphism may largely be a consequence
      of decreased enzyme stability resulting in compromised expression of holo-enzyme.
      Increased enzyme lability of CYP2C9.11 may be related to improper folding due to
      the disruption of conserved salt-bridge and hydrogen bonding contacts in the loop
      region between the J and J' helices of the protein.

PMID- 15970796
TI  - Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms
      with aspirin intolerance in asthmatics.
AB  - OBJECTIVES AND METHODS: The cysteinyl leukotriene receptor 2 (CYSLTR2) gene on
      chromosome 13q14.12-q21.1 encodes a receptor for CYSLTs, potent biological
      mediators in the pathogenesis of asthma, particularly that associated with
      aspirin intolerance (AIA). In an effort to discover additional polymorphism(s),
      the variant(s) of which have been implicated in asthma and aspirin intolerance,
      we scrutinized genetic polymorphisms of the CYSLTR2 gene, and evaluated this
      locus as a potential candidate for asthma. RESULTS: DNA sequencing in 24 Koreans
      of the 5-kb region of the CYSLTR2 gene, including the approximately 1500-bp
      promoter region, revealed four sequence variants: one in the 5'-flanking region
      (c.-819T>G), two in the 3'-flanking region (c.2078C>T and c.2534A>G), and one
      downstream of the gene (c.2545+297A>G). The SNP frequencies were 0.499 (c.
      819T>G), 0.351 (c.2078C>T), 0.429 (c.2534A>G), and 0.088 (c.2545+297A>G), and
      five haplotypes were constructed. The SNPs and haplotypes were not associated
      with risk of asthma development, but were significantly associated with aspirin
      intolerance. The frequencies of rare alleles on c.-819T>G, c.2078C>T, and
      c.2534A>G were higher in subjects with AIA than in subjects with aspirin-tolerant
      asthma (P=0.013-0.031). Asthmatics who had rare alleles for c.-819T>G, c.2078C>T
      or c.2534A>G exhibited a more pronounced fall in FEV1 after aspirin provocation
      than did those who carried the common allele (P=0.03-0.009). Asthmatics carrying
      ht2 (TTGA) also showed a more pronounced decrease in FEV1% after aspirin
      provocation than those carrying ht1 (GCGA) (P=0.006). These associations were
      even stronger when combined with LTC4S polymorphisms (-444A>C [c.-444A>C]) gene.
      CONCLUSION: CYSLTR2 polymorphisms are associated with aspirin intolerance in
      asthmatics.

PMID- 15970797
TI  - Characterization of the monomethylarsonate reductase and dehydroascorbate
      reductase activities of Omega class glutathione transferase variants:
      implications for arsenic metabolism and the age-at-onset of Alzheimer's and
      Parkinson's diseases.
AB  - There are two functional Omega class glutathione transferase (GST) genes in
      humans. GSTO1 is polymorphic with several coding region alleles, including an
      A140D substitution, a potential deletion of E155 and an E208K substitution. GSTO2
      is also polymorphic with an N142D substitution in the coding region. We
      investigated the effect of these variations on the enzyme's thioltransferase,
      dehydroascorbate reductase, monomethylarsonate reductase and dimethylarsonate
      reductase activities. Variant proteins were expressed in Escherichia coli and
      purified by Ni-agarose affinity chromatography. GSTO2-2 was insoluble and had to
      be dissolved and refolded from 8 M urea. The A140D and E208K substitutions in
      GSTO1-1 did not alter specific activity. The deletion of E155 caused a two- to
      three-fold increase in the specific activity with each substrate. This deletion
      also caused a significant decrease in the enzyme's heat stability. The E155
      deletion has been linked to abnormal arsenic excretion patterns; however, the
      available data do not clearly identify the cause of this abnormality. We found
      that GSTO2-2 has activity with the same substrates as GSTO1-1, and the
      dehydroascorbate reductase activity of GSTO2-2 is approximately 70-100-fold
      higher than that of GSTO1-1. The polymorphic N142D substitution had no effect on
      the specific activity of the enzyme with any substrate. The most notable feature
      of GSTO2-2 was its very high dehydroascorbate reductase activity, which suggests
      that GSTO2-2 may significantly protect against oxidative stress by recycling
      ascorbate. A defect in ascorbate metabolism may provide a common mechanism by
      which the Omega class GSTs influence the age-at-onset of Alzheimer's and
      Parkinson's diseases.

PMID- 15970798
TI  - Theophylline pharmacokinetics: comparison of Cyp1a1(-/-) and Cyp1a2(-/-) knockout
      mice, humanized hCYP1A1_1A2 knock-in mice lacking either the mouse Cyp1a1 or
      Cyp1a2 gene, and Cyp1(+/+) wild-type mice.
AB  - OBJECTIVES: Pharmacokinetics of theophylline was investigated in Cyp1(+/+) wild
      type mice, Cyp1a1(-/-) and Cyp1a2(-/-) knockout mice, and humanized hCYP1A1_1A2
      mice lacking either the mouse Cyp1a1 or Cyp1a2 gene. METHODS AND RESULTS: Animals
      received a single dose of theophylline (8 mg/kg i.p.), either alone or pretreated
      with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 10 microg/kg i.p.) 24 h prior to
      theophylline. We found that mouse or human CYP1A2 is the predominant enzyme for
      theophylline metabolism, the contribution of mouse or human CYP1A1 to
      theophylline metabolism is negligible, and another TCDD-inducible enzyme plays a
      minor role in 1-methyluric acid and 1,3-dimethyluric acid formation as well as
      enhanced theophylline clearance from the body. The half-life of elimination from
      plasma was more than four times longer in Cyp1a2(-/-) than Cyp1(+/+) mice and
      more than 10 times different after TCDD pretreatment. In humanized hCYP1A1_1A2
      mice lacking the mouse Cyp1a2 gene, the half-life of elimination from plasma was
      two to three times longer than that in Cyp1(+/+) mice and four to five times
      different after TCDD pretreatment. CONCLUSION: Replacement of mouse Cyp1a2 with a
      functional human CYP1A2 gene restored the ability to metabolize theophylline, and
      the metabolism changed to a humanized profile (i.e. 3-methylxanthine formation,
      not seen in the wild-type mouse). TCDD-pretreated hCYP1A1_1A2 Cyp1a2(-/-) mice
      exhibited enhanced theophylline metabolism and clearance, due to induction of the
      human CYP1A2 enzyme. Comparing the hCYP1A1_1A2 Cyp1a2(-/-) and wild-type mice
      with published clinical studies, we found theophylline clearance to be about 5
      times and 12 times, respectively, greater than that reported in humans.

PMID- 15970799
TI  - Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15
      and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293
      cells.
AB  - OBJECTIVES: SLCO1B1*5 and SLCO1B1*15 have been reported to reduce the clearance
      of pravastatin in healthy volunteers. However, there remains controversy in the
      effects of SLCO1B1*5 on the activity of OATP1B1 in vitro. In addition, the effect
      of SLCO1B1*15 on the function of OATP1B1 has not been studied using cDNA
      expression systems. Object of the present study was to study the influence of
      SLCO1B1*5, *15 and *15+C1007G, a novel haplotype found in a patient with
      pravastatin-induced myopathy, on the functional properties of OATP1B1 by
      transient expression systems of HEK293 and HeLa cells using endogenous conjugates
      and statins as substrates. METHODS: Transporting assays for endogenous substrates
      were performed using tritium labeled estradiol-17beta-D-glucuronide and estrone-3
      sulfate. Quantitation of pravastatin, atorvastatin, cerivastatin and simvastatin
      were carried out using HPLC tandem mass spectrometry. RESULTS: The transporting
      activities of cells expressing SLCO1B1*5, *15 and *15+C1007G decreased
      significantly but those of SLCO1B1*1b, *1a+C1007G and *1b+C1007G were not altered
      for all of the substrates tested except for simvastatin. Kinetic analysis of
      pravastatin and atorvastatin showed that Km values were not altered but Vmax
      values decreased significantly in cells expressing SLCO1B1*5, *15 and *15+C1007G.
      Immunocytochemical study showed that SLCO1B1*5, *15 and *15+C1007G proteins are
      localized not only at the plasma membrane but also in the intracellular space.
      CONCLUSIONS: These findings suggest that 521T>C, existing commonly in SLCO1B1*5,
      *15 and *15+C1007G, is the key single nucleotide polymorphism (SNP) that
      determines the functional properties of SLCO1B1*5, *15 and *15+C1007G allelic
      proteins and that decreased activities of these variant proteins are mainly
      caused by a sorting error produced by this SNP.

PMID- 15970805
TI  - Overweight and obese in gestational diabetes: the impact on pregnancy outcome.
AB  - OBJECTIVE: We sought to investigate the relationship between prepregnancy weight,
      treatment modality (diet or insulin), level of glycemic control, and pregnancy
      outcome. STUDY DESIGN: We recruited women with gestational diabetes (GDM) from
      inner city prenatal clinics. All women were instructed in the use of an
      intensified management protocol using memory reflectance meters. Outcomes were
      analyzed according to maternal prepregnancy body mass index (BMI, kg/m 2 )
      categories: normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), and obese
      (BMI > or =30), and by diet or insulin therapy and glycemic control (mean blood
      glucose <100 mg/dL = good control). Pregnancy outcome variables included a
      composite outcome (at least 1 of the following: neonatal metabolic complications,
      large-for-gestational age or macrosomic infants, NICU admission for >24 hours,
      and the need for respiratory support) (not including oxygen therapy). In addition
      to composite outcome, a bivariate analysis was performed for each single
      variable, including preeclampsia and cesarean section delivery. RESULTS: Four
      thousand and one women were enrolled. Obese women who achieved targeted levels of
      glycemic control had comparable pregnancy outcomes to normal weight and
      overweight women only when they were treated with insulin. Normal weight women
      treated with diet therapy who achieved targeted levels of glycemic control had
      good outcomes, but obese women treated with diet therapy who achieved targeted
      levels of glycemic control, nevertheless, had a 2- to 3-fold higher risk for
      adverse pregnancy outcome when compared with overweight and normal weight
      patients with well-controlled GDM. Women with GDM who failed to achieve
      established levels of glycemic control had significantly higher adverse pregnancy
      outcomes in all 3 maternal weight groups. CONCLUSION: In obese women with BMI >
      or =30 with GDM, achievement of targeted levels of glycemic control was
      associated with enhanced outcome only in women treated with insulin.

PMID- 15970804
TI  - Prospective first-trimester screening for trisomy 21 in 30,564 pregnancies.
AB  - OBJECTIVE: This study was undertaken to evaluate the performance of a 1-stop
      clinic for first-trimester assessment of risk (OSCAR) for trisomy 21 by a
      combination of maternal age, fetal nuchal translucency (NT) thickness, and
      maternal serum-free ss- human chorionic gonadotrophin (hCG) and pregnancy
      associated plasma protein-A (PAPP-A). STUDY DESIGN: OSCAR was carried out in
      30,564 pregnancies at 11 to 13 + 6 weeks. Patient-specific risks for trisomy 21
      and detection and false-positive rates were calculated. RESULTS: The median
      maternal age was 34 (range 15-49) years. Chromosomal abnormalities were
      identified in 330 pregnancies, including 196 cases of trisomy 21. The estimated
      risk for trisomy 21 was 1 in 300 or greater in 7.5% of the normal pregnancies, in
      93.4% of those with trisomy 21 and in 88.8% of those with other chromosomal
      defects. CONCLUSION: The most effective method of screening for chromosomal
      defects is by first-trimester fetal NT and maternal serum biochemistry.

PMID- 15970806
TI  - Implementation of first-trimester risk assessment for trisomy 21: ethical
      considerations.
AB  - The performance and evaluation of first-trimester risk assessment should meet
      standards of scientific and ethical excellence. Scientific standards are well
      understood. Ethical standards are less well understood. On the basis of the
      ethical concept of the physician as fiduciary, and the ethical principles of
      respect for autonomy, beneficence, and justice, we show that the obstetrician has
      an ethical obligation to routinely offer pregnant women first-trimester risk
      assessment in high quality centers. On the basis of the professional virtues of
      integrity and self-sacrifice, we then show that both obstetricians and
      specialists in risk assessment have a strict ethical obligation to identify,
      responsibly manage, and disclose both economic and noneconomic conflicts of
      interests, especially when they are hidden. We conclude that ethics is an
      essential dimension of implementation of first-trimester risk assessment for
      trisomy 21.

PMID- 15970808
TI  - Presidential address: from generation to generation.

PMID- 15970809
TI  - A prospective randomized trial of magnesium sulfate in severe preeclampsia: use
      of diuresis as a clinical parameter to determine the duration of postpartum
      therapy.
AB  - OBJECTIVE: The purpose of this study was to assess the use of the onset of
      diuresis in the determination of the duration of postpartum magnesium sulfate
      therapy among patients with severe preeclampsia. STUDY DESIGN: A prospective
      randomized trial of postpartum therapy with magnesium sulfate was conducted. The
      control group received 24 hours of therapy, and the study group received therapy
      until the onset of diuresis (urine output >100 mL/hr for 2 consecutive hours).
      The Student t test, chi 2 test, and Fisher's exact test were used for analysis of
      data; a probability value of <.05 was considered statistically significant.
      RESULTS: There were 50 patients in the control group and 48 patients in the study
      group. There was no difference in maternal demographic data, severe disease
      criteria, blood pressure, 24-hour postpartum urine output, or need for
      antihypertensive therapy. The study group had a significantly shorter duration of
      therapy, and no patient had eclampsia or required the re-initiation of therapy.
      CONCLUSION: The use of the onset of diuresis in the postpartum period as the
      determinant clinical parameter for the discontinuation of magnesium sulfate in
      patients with severe preeclampsia was associated with no untoward outcomes or
      need for the re-initiation of treatment.

PMID- 15970811
TI  - Brachial plexus injury: a 23-year experience from a tertiary center.
AB  - OBJECTIVE: The purpose of this study was to analyze the data on brachial plexus
      injury and its relationship with shoulder dystocia from a tertiary center for a
      23-year period. STUDY DESIGN: A review of the logbooks on labor and delivery and
      the nursery and the International Classification of Diseases codes identified all
      newborn infants with brachial plexus injury who were delivered at our center.
      RESULTS: During the 23 years (1980-2002), there were 89,978 deliveries, of which
      there were 85 cases of brachial plexus injury (1/1000 births) with vaginal
      delivery. The injury was permanent (> or =1 year) in 12% of the cases, and only 2
      cases have been litigated. Newborn infants that weighed > or =4 kg were
      significantly more common among those infants who had shoulder dystocia and
      brachial plexus injury than those infants without injury (odds ratio, 6.55; 95%
      CI, 2.30, 18.63). The rate of permanent brachial plexus injury was similar
      between the 2 groups. CONCLUSION: A case of brachial plexus injury occurs 1 time
      in every 1000 births, is permanent in 1 of every 10,000 deliveries, and is
      litigated 1 time for every 45,000 deliveries. The infrequent nature of injury may
      preclude prevention.

PMID- 15970814
TI  - Reevaluation of the relationship between amniotic fluid volume and perinatal
      outcome.
AB  - OBJECTIVE: Ultrasound estimation of amniotic fluid volume (AFI) is a critical
      component of antenatal surveillance. Alterations in AFI have classically been
      considered an indication of fetal compromise, but recent studies have called this
      into question. The present study was undertaken to reevaluate the relationship
      between AFI and perinatal outcome. STUDY DESIGN: The perinatal data base of the
      authors' institution was queried for all patients in a 6-year period who had AFI
      evaluated. Two groups, 1 high-risk and 1 low-risk, were evaluated to determine
      the relationship between AFI and gestational age. An additional high-risk group
      that had AFI determined within 48 hours of delivery was also used to correlate
      AFI with intrapartum and perinatal outcomes. Statistical analysis was performed
      using linear regression analysis to evaluate the correlation between AFI and
      gestational age or birth weight. Additional correlations were done using analysis
      of variance, chi-square, Fisher exact test, or Student t test. Interaction
      between variables was analyses using logistic regression analysis. RESULTS:
      Fourteen thousand seven hundred forty-seven AFI determinations in 4337 high-risk
      patients, and 1153 AFI determinations in 1153 low-risk patients were evaluated.
      There were no clinically significant correlations between AFI and gestational
      age. In the second high-risk group of 454 patients there was a significant
      correlation between polyhydramnios and large-for-gestational age infants,
      congenital anomalies, and an increase in cesarean section for delivery. There was
      an increased risk of nonreassuring fetal heart rate patterns during labor for the
      oligohydramnios patient, but only in preterm patients. There was no strong
      relationship between AFI and neonatal complications or length of stay in the
      neonatal intensive care unit. Logistic regression confirmed that AFI was not
      significantly correlated with perinatal outcome. CONCLUSION: The present study
      suggests that AFI is a weaker predictor of perinatal outcome than has been
      classically suggested. Although the AFI identification of polyhydramnios was
      helpful in identifying LGA fetuses and fetuses at risk for congenital
      abnormalities, oligohydramnios was a rather weak predictor of poor perinatal
      outcome.

PMID- 15970816
TI  - Use of fetal pulse oximetry among high-risk women in labor: a randomized clinical
      trial.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical role of fetal
      pulse oximetry to reduce cesarean delivery for a nonreassuring fetal heart rate
      tracing. STUDY DESIGN: Singletons > or =28 weeks were randomized to fetal pulse
      oximetry plus electronic fetal heart rate monitoring (monitoring + fetal pulse
      oximetry) or monitoring alone. RESULTS: Overall, 360 women in labor were
      recruited: 150 cases with monitoring+fetal pulse oximetry and 177 cases with
      monitoring alone were analyzed. Most demographic, obstetric, and neonatal
      characteristics were similar. Specifically, the gestational age, cervical
      dilation, and station of the fetal head were not differential factors. In
      addition, cesarean delivery for nonreassuring fetal heart rate tracing was not
      different between the group with monitoring+fetal pulse oximetry (29%) and the
      group with monitoring alone (32%; relative risk, 0.95; 95% CI, 0.75, 1.22).
      Likewise, cesarean delivery for arrest disorder was similar between the group
      with monitoring+fetal pulse oximetry (22%) and the group with monitoring alone
      (23%; relative risk, 1.05; 95% CI, 0.79, 1.44). However, the decision-to-incision
      time was shorter for the group with monitoring+fetal pulse oximetry (17.8 +/- 8.2
      min) than for the group with monitoring alone (27.7 +/- 13.9 min; P < .0001).
      CONCLUSION: The use of fetal pulse oximetry with electronic fetal heart rate
      monitoring does not decrease the rate of cesarean delivery, although it does
      alter the decision-to-incision time.

PMID- 15970818
TI  - Professional liability claims and Central Association of Obstetricians and
      Gynecologists members: myth versus reality.
AB  - OBJECTIVE: The purpose of this study was to survey members of the Central
      Association of Obstetricians and Gynecologists about professional liability
      claims. STUDY DESIGN: A survey was mailed to Central Association of Obstetricians
      and Gynecologists members regarding medical liability experience. RESULTS: Of the
      897 surveys mailed, 73% were completed. The responding 658 clinicians had been in
      practice for 17,136 years and had 1507 closed claims. The respondents had a claim
      every 11 years of practice and a trial every 69 years. Matched for years of
      practice, a case control comparison indicated that the litigation is
      significantly lower for female physicians (1.5 +/- 1.8) than for male physicians
      (2.2 +/- 2.0; P = .019) although the mean cases that were dropped or dismissed
      were higher for men (1.3 +/- 1.7 vs 0.8 +/- 1.4; P = .022). However, the mean
      number of trials, defense trial verdicts, and the settlement amounts were similar
      for both genders. CONCLUSION: We found that professional liability claims are
      uncommon and that the gender of the obstetrician-gynecologist influences the
      litigation profile.

PMID- 15970821
TI  - Vulvar disease: a pelvic floor pain disorder?
AB  - OBJECTIVE: The purpose of this study was to compare the rates of painful bladder
      syndrome and functional bowel disorders in women with vulvar disease and control
      subjects. STUDY DESIGN: In this cross-sectional survey, a questionnaire that
      contained validated outcome measures was administered to women who were seeking
      care in a vulvar disease clinic and in general gynecology clinics. RESULTS: Women
      who were seen at a vulvar disease clinic were 2.18 (95% CI, 1.19, 3.97) times
      more likely to have painful bladder syndrome and 2.13 (95% CI, 1.35, 3.35) times
      more likely to have functional bowel disorders than general gynecology clinic
      control subjects after multivariable analyses. CONCLUSION: Painful bladder
      syndrome and functional bowel disorders are more prevalent in women who are seen
      at a vulvar disease clinic than gynecology clinics control subjects. These
      associations may reflect a common origin for these disorders in certain women.
      These findings lay the groundwork for future research to investigate a potential
      "pelvic floor pain disorder," which is a disease entity that would combine the
      diagnostic criteria for vulvar, bladder, and bowel pain disorders.

PMID- 15970823
TI  - Placental expression of enzymes regulating prostaglandin synthesis and
      degradation.
AB  - OBJECTIVE: The purpose of this study was to characterize placental expression of
      the prostaglandin synthase enzymes cyclooxygenase (COX) -1 and -2 and
      prostaglandin dehydrogenase (PGDH, a degrading enzyme). STUDY DESIGN: Forty-one
      women between 20 and 37 weeks' gestation and 39 matched term controls with either
      spontaneous labor or premature rupture of membranes were enrolled in a
      prospective case-control study. The relative amounts of placental RNAs at
      delivery were determined using real-time polymerase chain reaction (PCR).
      RESULTS: Placental COX-1 RNA decreased with advancing gestational age at delivery
      (R(2) = 0.13, P = .001), and increased by 43% when chorioamnionitis was present
      (P = .006). Among patients presenting at term, oxytocin use was associated with
      30% lower expression of COX-1 (P = .01). COX-2 and PGDH were not associated with
      these variables. CONCLUSION: Placental COX-1 RNA at delivery decreases with
      advancing gestational age and with oxytocin use at term. Thus, expression of
      placental COX-1 is not constitutive. Placental expression of COX-2 and PGDH do
      not correlate with gestational age, chorioamnionitis, or oxytocin use.

PMID- 15970826
TI  - Comparison of multidose and single-dose methotrexate protocols for the treatment
      of ectopic pregnancy.
AB  - OBJECTIVE: The purpose of this study was to compare success rates of 643 patients
      who had ectopic pregnancy from the same database who were treated with multidose
      or single-dose methotrexate protocols. STUDY DESIGN: We compared demographics,
      gestational age, serum human chorionic gonadotropin, progesterone levels, ectopic
      sac size and volume, overall ectopic mass size and volume, ectopic cardiac
      activity, history of ectopic pregnancy, number of treatment days, methotrexate
      doses, and outcome in consecutive patients with ectopic pregnancy who were
      treated with methotrexate. RESULTS: Success rates were comparable between
      patients with multidose and single-dose therapy (95% vs 90%, respectively) as
      were human chorionic gonadotropin and progesterone levels, history of ectopic
      pregnancy (21.4% vs 21.7%, respectively), number of treatment days, gestational
      age, ectopic size, ectopic volume, and ectopic mass volume. Patients who received
      single-dose therapy were significantly heavier (146 vs 159 pounds), had greater
      ectopic cardiac activity (3.1% vs 10.3%), and received fewer methotrexate doses.
      CONCLUSION: This study suggests single-dose methotrexate therapy is as effective
      as multidose methotrexate therapy for the treatment of ectopic pregnancy.

PMID- 15970828
TI  - Extended-release formulations of oxybutynin and tolterodine exhibit similar
      central nervous system tolerability profiles: a subanalysis of data from the
      OPERA trial.
AB  - OBJECTIVE: This study was undertaken to compare the central nervous system (CNS)
      tolerability profiles of the extended-release formulations of oxybutynin chloride
      and tolterodine tartrate in the treatment of women with overactive bladder (OAB),
      as observed in the OPERA (Overactive bladder: Performance of Extended Release
      Agents) trial. STUDY DESIGN: The OPERA trial was a randomized, double-blind,
      active-control comparison of the efficacy and safety of extended-release
      oxybutynin (10 mg/d) and extended-release tolterodine (4 mg/d) given to 790 women
      with OAB for 12 weeks. The incidence of reported CNS events was compared between
      the treatment groups by using the Fisher exact test. RESULTS: The incidence of
      CNS adverse events was 9% and 8% for the oxybutynin and tolterodine treatment
      groups, respectively. The difference between groups was not statistically
      significant. All reported CNS adverse events were rated as mild or moderate in
      severity. There were no serious treatment-related adverse events in either group,
      and discontinuation because of a CNS adverse event was infrequent. CONCLUSION:
      The extended-release formulations of oxybutynin and tolterodine were observed to
      be associated with a similar low incidence of CNS adverse events, which were
      mostly mild or moderate in severity.

PMID- 15970831
TI  - Smoking in pregnancy revisited: findings from a large population-based study.
AB  - OBJECTIVE: The purpose of this study was to characterize the effect of smoking on
      the incidence of various pregnancy complications. STUDY DESIGN: A population
      based retrospective analysis with a perinatal database of 170,254 singleton
      pregnancies was performed. The rate of pregnancy complications was calculated in
      4 strata of smokers: Nonsmokers, 1 to 5 cigarettes per day, 6 to 10 cigarettes
      per day, and >10 cigarettes per day. Logistic regression was used to calculate
      odds ratios as measures of an association of smoking with various pregnancy
      complications after correction for confounding factors. RESULTS: The mean age of
      the study population was 29 +/- 4.8 years. The odds ratio for preeclampsia was
      0.64 (95 % CI, 0.59-0.70), for intrauterine growth restriction was 2.4 (95% CI,
      2.34-2.53), and for preterm delivery was 1.2 (95% CI, 1.13-1.28). CONCLUSION:
      Smoking decreased the incidence of preeclampsia in a dose-effect manner and was
      shown to increase the rate of intrauterine growth restriction and preterm
      delivery.

PMID- 15970833
TI  - Timing of prophylactic antibiotic administration in the uninfected laboring
      gravida: a randomized clinical trial.
AB  - OBJECTIVE: The purpose of this prospective study was to determine whether the
      timing of prophylactic antibiotics at cesarean delivery influences
      maternal/neonatal infectious morbidity. STUDY DESIGN: In this double-blind
      placebo-controlled trial, cefazolin was given at skin incision (group A) or at
      cord clamping (group B). Patients were eligible for the trial if they had labored
      and required a cesarean delivery. RESULTS: Over a 30-month period 303 patients
      with singleton pregnancies entered the trial; 153-group A, 149-group B.
      Demographics, indication for cesarean delivery (P = .54), and operative time (P =
      .999), as well as rates of endometritis (RR 0.67, 95% CI 0.42-1.07), wound
      infection (RR 0.84, 95% CI 0.45-1.55), neonatal sepis (RR 1.28, 95% CI 0.91
      1.79), and NICU admissions (RR 1.28, 95% CI 0.91-1.79) were similar between the 2
      groups. CONCLUSION: There was no difference in maternal infectious morbidity
      whether antibiotics were given before skin incision or at cord clamping.

PMID- 15970836
TI  - Repeat cesarean section and primary elective cesarean section: recently trained
      obstetrician-gynecologist practice patterns and opinions.
AB  - OBJECTIVE: This study was undertaken to determine opinions of obstetrician
      gynecologists regarding vaginal birth after cesarean (VBAC) section and elective
      cesarean section. STUDY DESIGN: A questionnaire was administered to obstetrician
      gynecologists attending 2 review courses. RESULTS: Of 500 obstetrician
      gynecologists, 304 completed the survey for a response rate of 61%. Most (92%)
      counseled VBAC candidates differently, and 84% quoted differential VBAC
      completion rates on the basis of the indication for prior cesarean section.
      Uterine rupture was virtually always discussed (99%). Pelvic floor risks were
      infrequently discussed with urinary incontinence, pelvic organ prolapse, and
      fecal incontinence discussed by less than one third of obstetricians (30%, 28%,
      and 25%, respectively). Fifty-nine percent of physicians would perform a primary
      elective cesarean section, and 67% would perform a primary elective cesarean
      section specifically to prevent pelvic floor disorders. CONCLUSION: Two thirds of
      recent graduates are willing to perform an elective cesarean section to prevent
      pelvic floor injury. Most offer VBAC; however, less than a third include risk of
      pelvic floor injury in their informed consent discussions.

PMID- 15970839
TI  - Accuracy of estimated fetal weight in shoulder dystocia and neonatal birth
      injury.
AB  - OBJECTIVE: This study was undertaken to determine whether there is any difference
      in the rate of error of estimated fetal weight (EFW) in cases of shoulder
      dystocia compared with controls. STUDY DESIGN: Women whose delivery was
      complicated by shoulder dystocia were studied and compared with a control group
      matched for parity, race, labor type (spontaneous or induced), and birth weight
      (BW). Accuracy (%) was defined as [(EFW-BW)/BW] x 100. The primary outcome of the
      study was rate of EFW underestimation error 20% or greater. RESULTS: During the 5
      year study period, there were 206 cases of shoulder dystocia that met all study
      criteria. There was no difference in the number of patients that had EFW
      underestimation error 20% or greater (shoulder dystocia 9.8% vs control 12.8%; P
      = .38). There was also no difference in the number of patients that had EFW
      underestimation error 20% or greater between shoulder dystocia with and without
      injury (injury 8.3% vs no injury 7.1%; P = .79). CONCLUSION: EFW underestimation
      error in cases of shoulder dystocia is an infrequent event and does not occur
      more often than in deliveries without shoulder dystocia.

PMID- 15970843
TI  - Presidential address: medical-legal issues in obstetrics and gynecology.
AB  - Patients, physicians, insurance companies, and legislators are expressing
      mounting concern in the area of malpractice insurance costs and its effect on the
      availability of health care. In 1986, the highest award in the history of medical
      legal claims, 1,200,000 US dollars, was paid. By 2001, the average award had
      increased to 3,500,000 US dollars. In the late 1970s the California's Medical
      Injury Compensation Reform Act (MICRA) was passed. This article discusses the
      elements of this important legislation and its effects on the cost of medical
      malpractice in California, the anatomy and pathophysiology of a medical-legal
      claim, and the characteristics of excellent expert witnesses and suggests some
      important elements of a redesigned system of medical-jurisprudence.

PMID- 15970844
TI  - Use of micro-dose human chorionic gonadotropin (hCG) after clomiphene citrate
      (CC) to complete folliculogenesis in previous CC-resistant anovulation.
AB  - OBJECTIVE: The purpose of this study was to compare the effectiveness of low-dose
      human chorionic gonadotropin (hCG) in the late follicular phase to induce
      ovulation and its endocrine response in patients who had previously failed to
      ovulate on clomiphene citrate (CC) alone. DESIGN: A total of 67 patients from a
      private tertiary infertility clinic, who had produced a dominant follicle 12 mm
      or larger but 20 mm or smaller on a prior CC cycle at 100 mg but had failed to
      ovulate, were prospectively randomly assigned to groups. Group 1 repeated the 100
      mg dose of CC but started a 200 IU hCG intramuscular injection daily when the
      largest follicle was 12 mm or larger mean diameter. Group 2 received a 150 mg
      dose of CC and both groups were monitored with transvaginal ultrasound and serum
      levels of E 2 , P 4 , and testosterone. Ultrasound measurements of follicle
      number and growth, ovulation, pregnancy rates, and serum hormonal levels were
      recorded and compared between the 2 groups. Analysis of variance and Student t
      test were used for statistical significance. RESULTS: The low-dose hCG group had
      significantly higher percentage of ovulatory cycles (57% vs 7% P < .001), peak E
      2 levels (378 pg/mL vs 125 pg/mL P < .01), and pregnancy rates (18% vs 0% P <
      .001). This group showed no evidence of premature leutinization from the hCG with
      preovulatory P 4 levels less than 1.0 ng/mL and a slight increase in androgen
      levels. CONCLUSION: The use of micro-dose hCG after CC in the late follicular
      phase results in continued follicle growth, increased E 2 levels, ovulation, and
      pregnancies. This treatment offers an efficient and cost-effective alternative
      before gonadotropin therapy for this type of patient.

PMID- 15970846
TI  - Factors that predict prematurity and preeclampsia in pregnancies that are
      complicated by systemic lupus erythematosus.
AB  - OBJECTIVE: The purpose of this study was to describe the outcomes of a 10-year
      cohort of pregnancies in patients with systemic lupus erythematosus and to
      evaluate clinical and laboratory markers for adverse outcomes. STUDY DESIGN: We
      reviewed all pregnancies in patients with systemic lupus erythematosus who were
      seen at Stanford University from 1991 to 2001. Univariate analyses were performed
      to identify potential risk factors for adverse outcomes. RESULTS: Sixty-three
      pregnancies in 48 women were identified. Approximately 35% of the pregnancies
      occurred in women with previous renal disease and 10% in women with previous
      central nervous system disease. Flares occurred in 68% of the pregnancies, the
      majority of which were mild to moderate. Preeclampsia complicated 12 pregnancies.
      Factors that were associated with premature delivery included prednisone use at
      conception (relative risk, 1.8), the use of antihypertensive medications
      (relative risk, 1.8), and a severe flare during pregnancy (relative risk, 2.0).
      Thrombocytopenia was associated with an increased risk of preeclampsia (relative
      risk, 3.2). CONCLUSION: Flares, most of which were mild to moderate, occurred
      most of the pregnancies in our cohort of patients with systemic lupus
      erythematosus. Thrombocytopenia, hypertension, and prednisone use may be
      predictive factors for particular adverse outcomes.

PMID- 15970850
TI  - Perimortem cesarean delivery: were our assumptions correct?
AB  - OBJECTIVE: The recommendation to perform a perimortem cesarean delivery within 4
      minutes of maternal cardiac arrest was introduced in 1986. This recommendation
      was based on the assumptions that cardiopulmonary resuscitation is ineffective in
      the third trimester because of aortocaval compression, and that fetal and perhaps
      maternal outcomes would be optimized by timely delivery. Our objective was to
      review the outcomes of perimortem cesarean deliveries to attempt to validate
      those assumptions. STUDY DESIGN: Ovid MEDLINE searches using maternal mortality,
      cardiopulmonary resuscitation, perimortem cesarean delivery, heart attack, and
      cardiac arrest from 1985 until 2004. Citations from bibliographies of identified
      publications were perused and cross-referenced for other potential articles. Case
      reports were included for analysis when mothers had complete cardiopulmonary
      arrest, and cardiopulmonary resuscitation had been initiated before cesarean
      delivery. RESULTS: There were 38 cases of perimortem cesarean delivery
      identified; 34 infants survived (3 sets of twins, 1 set of triplets); 4 other
      infants survived initially, but died several days after the deliveries from
      complications of prematurity and anoxia. Of the 34 infants (25-42 weeks'
      gestation), time of delivery after maternal cardiac arrest was available for 25.
      Eleven infants were delivered within 5 minutes, 4 were delivered from 6 to 10
      minutes, 2 were delivered from 11 to 15 minutes, and 7 were delivered more than
      15 minutes. Of 20 perimortem cesarean deliveries with potentially resuscitatable
      causes, 13 mothers were resuscitated and discharged from the hospital in good
      condition. One other mother was successfully resuscitated after the delivery, but
      died within 24 hours from complications related to her amniotic fluid embolism.
      In 12 of 18 reports that documented hemodynamic status, cesarean delivery
      preceded return of maternal pulse and blood pressure, often in a dramatic
      fashion. Eight other cases noted improvement in maternal status. Importantly, in
      no case was there deterioration of the maternal condition with the cesarean
      delivery. We wish to emphasize the large selection bias in this data. CONCLUSION:
      Published reports from 20 years support, but fall far from proving, that
      perimortem cesarean delivery within 4 minutes of maternal cardiac arrest improves
      maternal and neonatal outcomes.

PMID- 15970847
TI  - Cost-effectiveness analysis of prenatal population-based fragile X carrier
      screening.
AB  - OBJECTIVE: To investigate the cost-effectiveness of a widespread prenatal
      population-based fragile X carrier screening program. STUDY DESIGN: A decision
      tree was designed comparing screening versus not screening for the fragile X
      mental retardation protein 1 premutation in all pregnant women. Baseline values
      included a prevalence of fragile X mental retardation protein 1 premutations of
      3.3 per 1000, a premutation expansion rate of 11.3%, and a 99% sensitivity of the
      screening test. The cost of the screening test was varied from 75 US dollars to
      300 US dollars. A sensitivity analysis of the probabilities, utilities, and costs
      was performed. RESULTS: The screening strategy would lead to the identification
      of 80% of the fetuses affected by fragile X annually. Assuming the cost of 95 US
      dollars per test and only one child, the program would be cost effective at
      14,858 US dollars per quality-adjusted life-year. The screening strategy remained
      cost effective up to 140 US dollars per test and 1 child per woman or for 2
      children per woman up to a cost of 281 US dollars per test. CONCLUSION:
      Population-based screening for the fragile X premutation may be both clinically
      desirable and cost effective. Prospective pilot studies of this screening
      modality are needed in the prenatal setting.

PMID- 15970852
TI  - The effect of total hysterectomy on specific sexual sensations.
AB  - OBJECTIVE: Assess whether women note a change in aspects of arousal because of
      removal of the uterus and cervix. STUDY DESIGN: Between 1990 and 1992, 105 women
      were asked to report on their sexual function before and at 3, 8, and 18 months
      after undergoing a total hysterectomy. Results were analyzed by chi 2 . RESULTS:
      Hysterectomies were abdominal or vaginal, and 42% of subjects had ovaries removed
      and initiated estrogen replacement. Ease of arousal diminished in 24% and
      improved in 11%. Intensity of orgasms decreased in 15% and increased in 14%.
      Effects of nipple stimulation were usually preserved. Sexual satisfaction
      increased significantly. Seven women noted distinctly worse sexual function.
      CONCLUSION: An indicated total hysterectomy will likely increase sexual
      satisfaction and not change the effect of breast stimulation. The few women with
      disturbingly reduced sexual sensation deserve assessment and treatment.

PMID- 15970853
TI  - Comparison of perinatal grief after dilation and evacuation or labor induction in
      second trimester terminations for fetal anomalies.
AB  - OBJECTIVE: This study was undertaken to compare grief resolution after dilation
      and evacuation (D&E) or induction of labor (IOL) for second-trimester pregnancy
      termination. STUDY DESIGN: A prospective cohort of 49 women choosing second
      trimester abortion caused by fetal anomalies by either medical IOL or D&E.
      Depression was evaluated by using the Edinburgh Postnatal Depression Scale and
      bereavement was assessed by using the Perinatal Grief Scale with follow-up to 12
      months after pregnancy termination. Data were analyzed with chi 2 tests, Mann
      Whitney U tests, and independent and paired sample t tests. RESULTS: There was no
      significant difference in depression incidence on enrollment (61.9% D&E, 53.8%
      IOL, P = .579), at 4 months (23.5% D&E, 14.3% IOL, P = .252) or 12 months (27.3%
      D&E, 20.0% IOL, P = .696) or on the PGS at 4 months (74.1 vs 90.2, P = .351) or
      12 months (73.3 vs 86.4, P = .658). CONCLUSION: There is no significant
      difference in grief resolution among women who terminate a desired pregnancy by
      either medical or surgical abortion.

PMID- 15970854
TI  - Shoulder dystocia: are historic risk factors reliable predictors?
AB  - OBJECTIVE: Our purpose was to determine the rate of associated risk factors for
      shoulder dystocia from a large cohort of patients delivered within our Southern
      California perinatal program. STUDY DESIGN: A retrospective analysis was
      performed of patients delivered from January 1991 to June 2001. Patients with and
      without shoulder dystocia were identified from our computer-stored perinatal
      database and compared. Statistical methods used included: chi 2 test, t test,
      calculation of odds ratios, and Fisher exact test, as indicated. RESULTS: Among
      the 267,228 vaginal births during the study period, there were 1,686 cases of
      shoulder dystocia (rate 0.6%). Rates for operative vaginal delivery, diabetes,
      epidural use, multiparity, and postdatism were similar among cases with and
      without shoulder dystocia. The clinical triad of oxytocin use, labor induction,
      and birth weight greater than 4,500 g yielded a cumulative odds ratio of 23.2
      (95% CI 17.3-31.0) for shoulder dystocia, but its sensitivity and positive
      predictive value were only 12.4% and 3.4%, respectively. CONCLUSION: Historic
      obstetric risk factors for shoulder dystocia are not useful predictors for the
      event. Furthermore, although shoulder dystocia was observed more frequently with
      increasing birth weight, current limitations in estimating birth weight
      antenatally with accuracy preclude its practical use as a reliable predictor.

PMID- 15970858
TI  - Big infants in the neonatal intensive care unit.
AB  - OBJECTIVE: This study was undertaken to identify risk factors for prolonged
      neonatal intensive care unit (NICU) stay in macrosomic (> or = 4000 g) neonates.
      STUDY DESIGN: A population-based case-control study in which 799 cases of
      macrosomic neonates with a prolonged NICU stay were compared with macrosomic
      neonates without a prolonged stay (n = 1598). RESULTS: Significant risk factors
      included: 5-minute Apgar score less than 7: odds ratio (OR) = 43.1; fetal
      distress: OR = 3.0; birth length less than 20 inches: OR = 2.2; birth weight more
      than 5000 g: OR = 2.6; maternal diabetes: OR = 3.0; gestational age 37 to 38
      weeks: OR = 2.2; cephalopelvic disproportion: OR = 2.5; primary cesarean: OR =
      2.6; forceps/vacuum: OR = 1.7. No significant association was seen with labor
      induction/augmentation or dysfunctional/prolonged labor. CONCLUSION: Prolonged
      stay in macrosomic neonates was related to fetal distress measures and less to
      factors related to prolonged labor. Attention to intrapartum fetal status during
      labor with suspected macrosomia appears to be especially warranted.

PMID- 15970856
TI  - Abortion attitudes of pregnant women in prenatal care.
AB  - OBJECTIVE: This study was undertaken to describe abortion attitudes in a diverse
      cohort of pregnant women enrolled in prenatal care. STUDY DESIGN: A cross
      sectional interview study of 1082 demographically diverse gravid women enrolled
      in prenatal care at less than 20 weeks' gestation was performed. RESULTS: Most
      participants (92%) supported abortion availability. Half (50%) who were willing
      to consider an abortion would do so only in the first trimester. Among the gravid
      women willing to consider an abortion in the first or second trimester, 84% would
      do so after rape/incest or if their life was endangered and 76% would if their
      fetus had Down syndrome. Gravid women considering abortion were more likely to be
      white, older, have had a previous abortion, and to express distrust in the health
      care system. Women who would not consider abortion were more likely to be
      multiparous, married/living with partner, and to express greater faith and
      fatalism about their pregnancy outcome. CONCLUSION: Although most pregnant women
      enrolled in prenatal care support abortion availability, about half would only
      consider a first-trimester procedure. These findings underscore the need for
      early prenatal genetic counseling, screening, and testing.

PMID- 15970860
TI  - Incidence and management of abdominal sacrocolpopexy mesh erosions.
AB  - OBJECTIVE: This study was undertaken to evaluate the occurrence and management of
      mesh erosions in patients undergoing abdominal sacrocolpopexy. STUDY DESIGN: A
      retrospective chart review of the abdominal sacrocolpopexy procedure (n = 92)
      between 1997 and 2003 was performed. Patients with mesh erosion were identified.
      Incidence by graft type and treatment required for erosion resolution was
      analyzed with chi 2 and Fisher exact test. RESULTS: Erosions occurred in 7.6 %
      (7/92). Erosions were identified only in patients with Gore-Tex (3/33, 9%) or
      silicone-coated mesh (4/21, 19%) compared with none of 38 patients with
      polypropylene mesh (n = 24) or fascia (n = 14) grafts ( P = .068.). Partial
      excision of exposed graft resolved all 3 Gore-Tex erosions, compared with none of
      the silicone-coated mesh erosions ( P = .03). Complete graft removal was required
      to resolve silicone-coated mesh erosions. CONCLUSION: We observed a high rate of
      erosion with Gore-Tex and silicone-coated mesh. Partial graft excision was
      adequate for Gore-Tex erosions, but complete graft removal was necessary to
      resolve erosions associated with silicone-coated mesh.

PMID- 15970861
TI  - The role of an over-the-counter vaginal pH self-test device package insert: can
      subjects learn what the device is for and how to use it?
AB  - OBJECTIVE: This study was undertaken to determine whether subjects could read and
      understand the package insert of a vaginal pH self-test device to improve self
      diagnostic accuracy. STUDY DESIGN: This study was performed at 8 clinic locations
      with 206 women of varying ages, ethnicity, and education. A package insert
      explaining the indications and clinical facts associated with the use of a
      vaginal pH self-test device was used. A 16-item questionnaire was administered to
      assess comprehension. RESULTS: The cumulative probability of having 12 or more
      correct answers of 16 was P = .038, significantly different than by chance alone,
      representing 200 (97.1%) of subjects in this trial. CONCLUSION: The package
      insert for the vaginal pH self-test device was read and understood by subjects.
      Indeed, they correctly understood the role of vaginal pH as an aid in the
      diagnosis of vaginal symptoms while improving decisions to use an over-the
      counter antifungal medication or to see a health care provider.

PMID- 15970864
TI  - Birth rate and its correlation with the lunar cycle and specific atmospheric
      conditions.
AB  - OBJECTIVE: This study was undertaken to use the Arizona State birth certificate
      database for Phoenix metropolitan hospitals, in conjunction with National Weather
      Service records to determine whether there is a relationship between birth rate
      and meteorologic or lunar conditions. This study attempts to dispel or lend
      significance to beliefs among hospital staff that the phase of the moon and/or
      meteorologic conditions are related to birth rate. STUDY DESIGN: Birth records
      were limited to spontaneous vaginal deliveries, 37 to 40 weeks' gestation, in
      Phoenix, between 1995 and 2000 (n = 167,956). Daily birth counts were merged with
      daily surface weather statistics from the National Weather Service for Sky Harbor
      Airport, and records of lunar phase for the same period. RESULTS: The analyses
      revealed no significant correlates of birth rate. CONCLUSION: Although there
      exists a popular belief that the phase of the lunar cycle and weather conditions
      affect birth rate, no such evidence was found in this study.

PMID- 15970865
TI  - Is advanced maternal age an independent risk factor for uteroplacental
      insufficiency?
AB  - OBJECTIVE: To determine whether maternal age 35 years or older is an independent
      risk factor for uteroplacental insufficiency and thus an independent indication
      for antepartum testing. STUDY DESIGN: A retrospective cohort analysis was
      performed of all deliveries at Los Angeles County-University of Southern
      California Women's and Children's Hospital between August 1, 1995, and September
      1, 2003. Women with documented indications for antepartum testing, fetal
      anomalies, or delivery prior to 34 weeks were excluded from analysis. Markers of
      uteroplacental insufficiency included stillbirth, birth weight less than the 10th
      percentile, fetal distress, cesarean section for fetal distress, oligohydramnios,
      meconium passage, and 5-minute Apgar score less than 7. RESULTS: Indications for
      antepartum testing were significantly more common in women 35 years or older
      (33.2% versus 27.0%). After excluding women with indications for antepartum
      testing, anomalous fetuses, and women delivering prior to 34 weeks, stillbirth
      was twice as common in women 35 years and older. However, among stillbirths,
      growth restriction occurred with similar frequency in the older (28.6%) and
      younger (25.0%) cohorts. Among live births, 2 markers of uteroplacental
      insufficiency, intrapartum fetal distress (5.7% versus 4.1%) and cesarean
      delivery for fetal distress (4.0% versus 2.4%) were significantly more common in
      the older cohort. All other markers of uteroplacental insufficiency were observed
      with similar frequency in the 2 groups. CONCLUSIONS: After excluding women with
      other indications for antepartum testing, fetal anomalies, and delivery prior to
      34 weeks, stillbirth was twice as common in women 35 years of age or older as in
      those younger than 35 years. The increased rate of stillbirth does not appear to
      be explained by a higher rate of uteroplacental insufficiency.

PMID- 15970868
TI  - Three-dimensional ultrasound-guided embryo transfer: a preliminary study.
AB  - OBJECTIVE: Embryo transfer techniques have emerged as 1 of the most important
      variables during in vitro fertilization. Two-dimensional ultrasound guidance is
      an integral part of this procedure and a method to monitor catheter passage
      through the cervix into the endometrial cavity. Catheter placement may better be
      achieved with 3-dimensional monitoring to assess the relationship of the catheter
      tip to the uterine cavity. The purpose of this study was to compare the precision
      of catheter placement and position by 2- and 3-dimensional ultrasound. STUDY
      DESIGN: Twenty-four patients were studied. The cervix, uterus, and endometrial
      cavity were prescreened in 2 dimensions at the midline in the longitudinal plane
      of the uterus. Embryo transfers were then performed under 2-dimensional guidance.
      After satisfactory catheter placement and transfer of the embryos, the catheter
      was held in place for 60 to 120 seconds. During this interval, an automated,
      single sweep of the uterus and endometrial cavity was performed for net volume
      acquisition. All images were stored and retrospectively reviewed. Embryo transfer
      catheter placement with 2-dimensional ultrasound guidance was then compared with
      the images obtained in 3 simultaneous planes. RESULTS: Visualization of the
      embryo catheter tip with 2-dimensional ultrasound was achieved in all patients.
      These images suggested that the catheter was 2 cm from the uterine fundus and in
      the midline. Satisfactory 3-dimensional images for review and comparison were
      obtained in 21 of 24 patients. Three-dimensional ultrasound images confirmed
      placement and agreed with findings of 2-dimensional ultrasound images in 17 of 21
      patients. In 4 patients, the catheter tip on 3-dimensional ultrasound was
      observed to be displaced either anteriorly or laterally from the ideal region as
      suggested by 2-dimensional ultrasound. In 1 case, the catheter tip on 3
      dimensional ultrasound was observed to be far laterally in the region of the
      uterine cornua. CONCLUSION: Two-dimensional ultrasound-guided embryo transfer
      continues to be the standard for image-guided transfers. Data of the present
      study suggest that the precision of catheter tip placement and consequently
      embryo transfer may be improved with 3-dimensional imaging. Four of 21 patients
      studied had catheter tip placement in a different and less-than-ideal area when
      studied with 3-dimensional ultrasound. Three-dimensional imaging may provide an
      improvement in embryo transfer technique and have a positive impact on overall
      pregnancy rates.

PMID- 15970870
TI  - Transvaginal placement of cervicoisthmic cerclage: report on pregnancy outcome.
AB  - OBJECTIVE: This study was undertaken to review pregnancy course and outcome in 56
      pregnancies after the placement of a cervicoisthmic cerclage transvaginally.
      STUDY DESIGN: Fifty-three pregnant patients with unique indications such as
      previous failure of conventional cerclages or compromised cervical anatomy,
      underwent transvaginal placement of a cervicoisthmic cerclage during pregnancy.
      RESULTS: There was 100% fetal survival. Preterm birth rate was 32% and births at
      less than 30 weeks occurred in 21% of our patients. In 6 patients, the suture was
      not removed and 3 patients had an additional gestation with the same suture.
      Serious complications included 1 instance of intraoperative bladder laceration
      and 1 of intrapartum cervical tear. Minor complications included a postoperative
      hematoma and transient urinary retention with pelvic pain in 2 patients.
      CONCLUSION: The placement of transvaginal cervicoisthmic cerclage was associated
      with favorable pregnancy outcome and may be considered as a suitable safe
      alternative to the transabdominal cerclage.

PMID- 15970873
TI  - Comparison of the quality of life after nonsurgical radiofrequency energy tissue
      micro-remodeling in premenopausal and postmenopausal women with moderate-to
      severe stress urinary incontinence.
AB  - OBJECTIVE: This study was undertaken to determine the effect of menopause and
      hormone replacement therapy (HRT) on incontinence quality of life (I-QOL) score
      improvement in women with moderate-to-severe stress urinary incontinence (SUI)
      after nonsurgical, transurethral radiofrequency energy (RF) tissue micro
      remodeling. STUDY DESIGN: Retrospective review of prospective, randomized,
      controlled clinical trial. Women with moderate-to-severe SUI were analyzed by
      menopausal status and HRT use for 10-point or greater I-QOL score improvement (an
      increase associated with subjective and objective SUI improvement). RESULTS: RF
      micro-remodeling resulted in 81% of subjects achieving 10-point or greater I-QOL
      score improvement versus 49% of sham subjects at 12 months ( P = .04). Outcomes
      did not differ statistically when premenopausal (85%), postmenopausal using HRT
      (70%), and postmenopausal not using HRT (71%) groups were compared. CONCLUSION:
      Menopausal status and HRT demonstrated no impact on the quality of life
      improvement experienced by women with moderate-to-severe SUI who underwent RF
      tissue micro-remodeling.

PMID- 15970875
TI  - Outcomes of pregnancies achieved by donor egg in vitro fertilization--a
      comparison with standard in vitro fertilization pregnancies.
AB  - OBJECTIVE: Prior studies on donor egg in vitro fertilization (DE-IVF) outcomes
      have been limited by the lack of an appropriate control group. Here, we review
      the obstetric and perinatal outcomes of pregnancies achieved by DE-IVF and
      compare these pregnancies with those of women who also needed similar assisted
      reproductive techniques, of similar socioeconomic status, and cared for by a
      small group of 8 physicians applying consistent diagnostic and treatment
      approaches. STUDY DESIGN: A retrospective review of 50 consecutive pregnancies
      achieved by DE- IVF and 50 consecutive pregnancies achieved by standard IVF (STD
      IVF) was performed. Comparisons were made for demographic and medical confounding
      factors and for outcome measures. RESULTS: The 2 groups were nearly identical for
      gravidity, parity, and multiple gestations but did vary in maternal age. Average
      age of patients receiving DE-IVF was 41.9(+/-5.1), whereas the STD-IVF averaged
      37.7(+/-3.6) years ( P < .001). Key obstetric outcomes did not differ between the
      2 groups with the exception of pregnancy-induced hypertension. In patients with
      DE-IVF, 26% had pregnancy-induced hypertension (PIH) develop, whereas this
      occurred in only 8% of the STD-IVF group ( P = .02). Examining nulliparous
      patients only, 37.1% of DE-IVF had PIH develop, whereas only 8% of STD-IVF group
      achieved that diagnosis ( P < .003). An analysis with a multiple logistic
      regression in nulliparous patients found odds ratios of 7.1 (95% CI, 1.4-36.7) in
      DE versus STD-IVF, odds ratio 4.9 (95% CI, 1.3-18.3) for multiple gestation
      versus singleton, and odds ratio 1.0 (95% CI, 0.9-1.1) for maternal age.
      CONCLUSION: Nulliparous pregnancies achieved by DE-IVF are associated with an
      increased risk of PIH; however, excellent outcomes can still be expected.

PMID- 15970877
TI  - Treatment of non-albicans Candida vaginitis with amphotericin B vaginal
      suppositories.
AB  - OBJECTIVE: This study was undertaken to investigate whether amphotericin B
      vaginal suppositories would be effective in the treatment of non- albicans
      Candida vaginitis in women who failed conventional therapy. STUDY DESIGN: Thirty
      two patients were identified with non- albicans Candida vaginitis. These patients
      were treated with conventional antifungal agents. Ten patients had persistence of
      the non- albicans Candida infection after treatment. Amphotericin B 50-mg vaginal
      suppositories were given nightly for 14 days to this subgroup of treatment
      failures. RESULTS: Of 10 women, 8 (80%) who were treated with amphotericin B
      vaginally initially showed no further infection. One of the treatment successes
      had 2 recurrences and responded to a second course of amphotericin B but failed a
      third course. If this patient is considered a treatment failure, then
      amphotericin B vaginal suppositories were successful in 70% of patients. The
      medication was well tolerated and local side effects were minimal. CONCLUSION:
      Amphotericin B vaginal suppositories are a viable treatment option for refractory
      vaginitis caused by non- albicans Candida .

PMID- 15970880
TI  - Embryo fragmentation as a determinant of blastocyst development in vitro and
      pregnancy outcomes following embryo transfer.
AB  - OBJECTIVE(S): To determine how the type of embryo fragmentation on day 3 affects
      progression of human embryos to blastocyst and pregnancy rates following embryo
      transfer. STUDY DESIGN: Retrospective analysis of all in vitro fertilization
      cycles in patients < or =40 years of age or younger from January 2002 through
      December 2003, during which time surplus day 3 embryos were transferred to
      blastocyst medium for extended culture. All embryos (4 cells or more) not
      suitable for transfer or freezing 72 hours following in vitro fertilization were
      placed into microdroplets (60 microL) of blastocyst medium and cultured for an
      additional 48 hours to assess blastocyst formation. Normal blastocyst development
      required blastulation, a visible inner-cell mass, trophectoderm cells covering
      60% of the inner zona surface and thinning of the zona. The rate of blastocyst
      formation was then analyzed (chi 2 and analysis of variance) against the type of
      fragmentation 72 hours after insemination. Pregnancy outcomes were analyzed with
      respect to the pattern of fragmentation in cleaving embryos transferred after 3
      days of culture. RESULTS: A total of 1566 embryos were cultured beyond day 3 of
      development of which 229 (14.6%) reached the blastocyst stage and were frozen.
      Embryos exhibiting no fragmentation or type I fragmentation had significantly
      higher blastocyst development rates (27.9% and 19.9%) than embryos with type 2 or
      3 fragmentation (13.9 and 8.8, respectively; P < .001). No embryos with type 4 or
      5 fragmentation progressed to blastocyst. The average type of fragmentation in
      transferred embryos correlated with pregnancy outcome and embryo age.
      CONCLUSION(S): More pervasive embryo fragmentation was associated with a
      decreasing rate of blastocyst development with day 3 embryos. To the extent that
      blastocyst development rates of day 3 embryos is an index of embryo viability,
      our findings establish that careful classification of the type of embryo
      fragmentation is important in selection of day 3 embryos for transfer. Recent
      reports of associations among embryo fragmentation, aneuploidy, apoptosis, and
      patient age support these conclusions.

PMID- 15970886
TI  - Patient satisfaction with the prenatal care provider and the risk of cesarean
      delivery.
AB  - OBJECTIVES: This study was undertaken to assess the relationship between patient
      satisfaction with the prenatal care provider and a gravid woman's risk of
      cesarean delivery. STUDY DESIGN: Medical records of 586 consecutive deliveries in
      a single obstetrics department were reviewed. The delivery mode was correlated to
      the providers' overall patient satisfaction score as measured by an ongoing mail
      survey. Mann-Whitney U tests and 2-tailed t tests were used. RESULTS: On the
      basis of the prenatal provider, not the delivering physician, the cesarean
      section delivery rates fell into 3 groups: low rate, average rate, and high rate.
      There is a significant difference in both the cesarean delivery rate and the
      patient satisfaction survey scores between the prenatal providers in the high-
      and low-rate groups. CONCLUSION: Higher patient satisfaction scores is correlated
      with a lower cesarean delivery rate.

PMID- 15970883
TI  - An isolated intracardiac echogenic focus as a marker for aneuploidy.
AB  - OBJECTIVE: This study was undertaken to evaluate the relationship of an isolated
      fetal intracardiac echogenic focus in a population of patients with a mixed risk
      for aneuploidy when presenting for prenatal diagnosis. STUDY DESIGN: All women
      referred to our institution for screening ultrasound were prospectively evaluated
      for the presence of an intracardiac echogenic focus in the fetal heart. Each
      patient was evaluated for the presence of clinical risk factors including
      ultrasound findings, biochemical screening, and maternal age. The population of
      patients was then described and neonatal outcomes were obtained. RESULTS: A total
      of 10,875 patients were referred and 176 cases of fetal intracardiac echogenic
      foci were evaluated. There was an overall prevalence of 1.6% in our population.
      The patients with other ultrasound findings and/or maternal age older than 35
      years who underwent amniocentesis had 3 abnormal karyotypes identified and had
      identifiable risk factors. In the group less than 35 years, the relative risk was
      2.55 of having an amniocentesis for an isolated echogenic focus (with no cases of
      fetal aneuploidy found) in comparison with our referred group of nonadvanced
      maternal age patients without any ultrasound markers or findings. CONCLUSION:
      This isolated echogenic finding appears to be a benign variant and not an
      increased risk for fetal aneuploidy. The chromosomal abnormalities were seen in
      the group with risk factors including maternal age and/or other ultrasound
      findings. Evaluation of maternal age, biochemical markers, and ultrasound markers
      should be used together to help determine the risk of patients with an isolated
      echogenic focus.

PMID- 15970888
TI  - Pregnancy rates after transfer of cryopreserved blastocysts cultured in a
      sequential media.
AB  - OBJECTIVE: This study was undertaken to determine the pregnancy rate after
      transfer of cryopreserved blastocysts. STUDY DESIGN: Retrospective review of 61
      patients from January 1, 2002, to December 31, 2003, who were transferred with
      blastocyst embryos cryopreserved on day 5 or 6 after culture in a sequential
      media. The cryopreserved blastocysts were thawed by using a 7-step dilution
      process after rapid thawing half hour to 2 hours before embryo transfer. RESULTS:
      The pregnancy rate after transfer of 61 patients with cryopreserved blastocysts
      was 66%, with 49% having cardiac activity. The pregnancy rate after transfer of 3
      blastocysts was 71% and after transfer of 2 blastocysts was 66%. The pregnancy
      rate of blastocysts cryopreserved after intracytoplasmic sperm injection was 56%.
      CONCLUSION: Cryopreservation and transfer of blastocysts appears to be a reliable
      procedure, and that the human blastocyst can be cryopreserved and thawed without
      a significant loss of viability.

PMID- 15970890
TI  - A novel model of polyhydramnios: amniotic fluid volume is increased in aquaporin
      1 knockout mice.
AB  - OBJECTIVE: To test the hypothesis that amniotic fluid volume is increased in
      aquaporin 1 knockout mice. STUDY DESIGN: Transgenic mice deficient in aquaporin 1
      protein were generated by targeted gene disruption, as described previously.
      After a cesarean section was performed, intact, individual gestational sacs were
      removed from the uterus and weighed. Amniotic fluid volume, osmolality, and fetal
      and placental weights were determined. Data were analyzed by a 1-way analysis of
      variance for ranks; Dunn's post hoc test was used to analyze significant trends.
      RESULTS: Analysis of 16 litters showed 35 wild-type, 52 heterozygote, and 33
      aquaporin 1 knockout mice. The knockout mice had a greater volume of amniotic
      fluid and lower amniotic fluid osmolality than their wild-type and heterozygote
      counterparts. There were no significant differences in fetal or placental weights
      among the groups. CONCLUSIONS: Aquaporin 1 null fetuses produce a greater volume
      of more dilute amniotic fluid. Our findings show that aquaporin 1 water channels
      in fetal membranes may contribute to amniotic fluid volume regulation. We
      speculate that idiopathic polyhydramnios may be associated with a deficiency of
      aquaporin 1 channels in human fetal membranes. Transgenic aquaporin 1 knockout
      mice provide a unique animal of polyhydramnios.

PMID- 15970893
TI  - Evaluation of the pregnancy prolongation index (PPI) as a measure of success of
      obstetric interventions in the prevention of preterm birth and associated
      morbidities.
AB  - OBJECTIVE: This study was undertaken to evaluate the validity of the pregnancy
      prolongation index (PPI) as a measure of preterm labor treatment success. STUDY
      DESIGN: Analysis of prospectively collected maternal and neonatal data from a
      national clinical database (Matria Healthcare). Included were patients with
      singleton, twin, and triplet pregnancies who had outpatient surveillance
      initiated between 18 and 34 weeks and delivered at 24 to 36 6/7 weeks' gestation
      with NICU admission. Each patient's PPI score was calculated via the following
      equation: [(gestational age at delivery - gestational age at start of treatment)
      / (37.0 - gestational age at start of treatment)] x 100%. The impact of
      increasing PPI score was measured against NICU length of stay as a surrogate
      gauge of neonatal morbidity. Data were further stratified by gestational type and
      reason for delivery. RESULTS: Pregnancy outcomes of 12,642 patients (6,642
      singletons, 4,326 twins, and 1,674 triplets) were analyzed. The PPI score
      increased in a direct, inverse linear relationship with decreasing number of NICU
      days. CONCLUSION: The PPI is a sensitive measure for the evaluation of treatment
      success in the inhibition of preterm labor and delivery.

PMID- 15970897
TI  - Effect of oral versus transdermal steroidal contraceptives on androgenic markers.
AB  - OBJECTIVE: The purpose of this study was to compare biochemical androgen profiles
      in women treated with the contraceptive patch versus an oral contraceptive (OC).
      STUDY DESIGN: Twenty-four healthy women were randomly assigned to receive 3
      cycles of either the contraceptive patch (ethinyl estradiol [EE] 20 microg/d and
      norelgestromin 150 microg/d) or OC (EE 35 mug and norgestimate 250 microg). Blood
      samples were taken at baseline and end of treatment. Serum levels of sex hormone
      binding globulin (SHBG), total testosterone (T), androstenedione (A),
      dehydroepiandrosterone sulfate (DHEAS), dihydrotestosterone (DHT), and 3alpha
      androstanediol glucuronide (3alpha-diol G) were quantified by immunoassay
      methods; free T was calculated. The paired t and Student t tests were used for
      statistical analysis. RESULTS: Nineteen women completed the study (patch, n = 10;
      OC, n = 9). Despite a 1.6-fold relative increase in SHBG levels with the patch
      versus OC (449% vs 274%, P = .03), free T decreased equally in both groups (patch
      60%, P < .0001; OC 59%, P < .0001). DHEAS decreased by 26% in the patch group (P
      < .01) and 32% in the OC group (P < .001). 3alpha-diol G was reduced by 52% in
      the patch group (P < .0001) and 51% in the OC group (P < .0001). In addition, the
      OC was associated with significant decreases in A and DHT. CONCLUSION: The
      contraceptive patch had an effect comparable to the OC on several key androgenic
      markers. Given these biochemical findings, the contraceptive patch has
      significant potential as a therapeutic agent for disorders of androgen excess.

PMID- 15970899
TI  - Successful external cephalic version after amnioinfusion in a patient with
      preterm premature rupture of membranes.
AB  - After hospitalization subsequent to preterm premature rupture of membranes at 29
      weeks, our patient was scheduled for induction of labor at 34 weeks. When the
      fetus was found to be breech with oligohydramnios, amnioinfusion was performed to
      facilitate external cephalic version, and this successful procedure enabled the
      patient to deliver vaginally.

PMID- 15970898
TI  - Serious pregnancy complications in a patient with previously undiagnosed
      carnitine palmitoyltransferase 1 deficiency.
AB  - Fetal defects in mitochondrial beta-oxidation have been linked with an increased
      risk for acute fatty liver of pregnancy and preeclampsia-related conditions. A
      woman with previously undiagnosed carnitine palmitoyltransferase 1 deficiency
      experienced hemolysis, elevated liver enzymes, low platelets-like syndrome late
      in her first pregnancy with an unaffected fetus. Carnitine palmitoyltransferase 1
      deficiency should be considered as a potential cause of life-threatening
      complications of pregnancy.

PMID- 15970900
TI  - Congenital chylothorax in three siblings.
AB  - Congenital chylothorax is an uncommon condition, resulting from lymphatic
      accumulation in the fetal thorax; affected siblings are extremely rare. We report
      a woman who delivered 3 children with congenital chylothorax; each case was
      managed differently, including the use of ex utero intrapartum treatment (EXIT)
      with the third pregnancy.

PMID- 15970901
TI  - Acquired von Willebrand disease: management of labor and delivery with
      intravenous dexamethasone, continuous factor concentrate, and immunoglobulin
      infusion.
AB  - Acquired von Willebrand disease is a rare bleeding disorder that can lead to
      complete absence of clotting factor 8 and von Willebrand factor. Recently, the
      hematologic literature has reported continuous infusion of factor concentrates
      and intravenous immunoglobulin as an improved therapy for active bleeding and
      prophylaxis in patients who are anticipating surgery with congenital von
      Willebrand disease. We describe the first case of a pregnant woman with acquired
      von Willebrand disease who underwent the described therapy during delivery.

PMID- 15970902
TI  - Anterior pseudomeningocele evaluated as a pelvic mass.
AB  - OBJECTIVE: The differential diagnosis of pelvic masses is broad, and
      nongynecologic causes should be considered. RESULTS: A patient with a presumed
      adnexal mass was diagnosed eventually with an anterior pseudomeningocele.

PMID- 15970903
TI  - A pregnant patient with renal vein thrombosis successfully treated with low-dose
      thrombolytic therapy: a case report.
AB  - OBJECTIVE: An 18-year-old woman with membranous glomerulonephritis was seen at 26
      weeks of gestation with a right renal vein thrombosis with 95% occlusion.
      RESULTS: Both thrombolytic and anticoagulation therapy were administered with
      success. CONCLUSION: Thrombolytic therapy, when used cautiously under intensive
      care settings, may prolong gestation to enhance the chances of a favorable
      outcome.

PMID- 15970904
TI  - Septuplet placenta: a case report.
AB  - OBJECTIVE: On November 19, 1997, 7 liveborn infants (4 boys and 3 girls) were
      delivered by cesarean delivery at 30.5 weeks gestational age. The pregnancy was
      the result of artificial induction of ovulation. STUDY DESIGN: The septuplet
      placenta was evaluated with a standard and systematic procedure for placentas of
      multiple births that revealed a septamnionic, septchorionic architecture with 5
      fused and 2 unfused placentas. RESULTS: Each of the 7 umbilical cords contained 3
      vessels. Two cords were velamentous; the remaining 5 cords were inserted
      eccentrically. The ratio of combined birth weights of the 7 infants to total
      placental weight (7.52:1) correlated with normograms of singleton and twin
      gestations. CONCLUSION: This ratio and additional calculations were used for
      comparison and for additional clinicopathologic correlations.

PMID- 15970905
TI  - Pathologic uterine torsion associated with placental abruption, maternal shock,
      and intrauterine fetal demise.
AB  - Torsion of the uterus is a rare obstetric complication. This report describes a
      270-degree uterine torsion associated with placental abruption, maternal shock,
      and fetal demise. At laparotomy, the uterus and ovaries were necrotic. This
      patient presented in a manner typically managed by labor induction, thus delaying
      her diagnosis of uterine torsion.

PMID- 15970906
TI  - A unique case of conjoined triplets.
AB  - A unique case of conjoined triplets that was characterized as tricephalus,
      tetrabrachius, and tetrapus parapagothoracopagus is presented. Antenatal
      diagnosis of the conjoined triplet was made at 22 weeks of gestation with 2
      dimensional ultrasonography and magnetic resonance imaging. Pregnancy was
      terminated by hysterotomy, and diagnosis of conjoined triplets was confirmed
      postnatally.

PMID- 15970907
TI  - Plasmapheresis for the treatment of intrahepatic cholestasis of pregnancy
      refractory to medical treatment.
AB  - Pruritus associated with intrahepatic cholestasis of pregnancy (ICP) is usually
      mild but some cases are refractory to medical treatment. We report a case of
      intractable ICP that was successfully treated with plasmapheresis. Plasmapheresis
      should be considered for ICP that is refractory to traditional therapies.

PMID- 15970909
TI  - Letter to the editor: re - editorial by Wapner.

PMID- 15970910
TI  - Concerns about differential use of LMP in ultrasound-based EDC estimation.

PMID- 15970911
TI  - Does reducing postdates induction of labor through the use of first-trimester
      ultrasound improve clinical outcomes?

PMID- 15970912
TI  - Menorrhagia: the 80 mL criterion and the usefulness in clinical practice.

PMID- 15970917
TI  - An experience of a lifetime.

PMID- 15970918
TI  - Time-contingent dosing of an opioid analgesic after tonsillectomy does not
      increase moderate-to-severe side effects in children.
AB  - As part of a randomized clinical trial that compared three different analgesic
      dosing regimens ( Sutters et al., 2004 ), the purpose of this study, in children
      who underwent tonsillectomy, was to determine whether around-the-clock (ATC)
      dosing of acetaminophen with codeine, compared with as-needed (PRN) dosing,
      increased the frequency of moderate-to-severe opioid-related side effects (i.e.,
      daytime sedation, lightheadedness, nightmares, nausea, vomiting, and
      constipation) in the first 3 days after surgery. Because no differences were
      found in pain intensity scores and in the amount of analgesic administered
      between the two ATC groups (i.e., with and without coaching), for these analyses,
      the two groups were combined ( n = 52) and compared with the PRN group ( n = 28).
      Each side effect was recoded into a dichotomous response (i.e., 0 = did not have
      symptoms or had slight symptoms; 1 = symptoms that were moderate, severe, or very
      severe) to provide an adequate sample size in each cell for the statistical
      analyses. No differences were found in the frequency of moderate-to-severe side
      effects between the ATC and PRN groups at any of the postoperative assessments.
      The number of children who reported moderate-to-severe daytime sedation decreased
      over time in both the PRN ( p = .02) and ATC groups ( p = .01). Children in the
      ATC groups reported a statistically significant decrease over time in vomiting (
      p = .001) and feeling lightheaded or dizzy ( p = .003), and a significant
      increase in constipation ( p = .018). Except for daytime sedation, changes, over
      time, in the frequency of moderate-to-severe side effects were not observed in
      the PRN group.

PMID- 15970919
TI  - Changes in the meaning of pain with the use of guided imagery.
AB  - The purpose of this study is to determine how verbal descriptions of pain change
      with the use of a guided imagery technique. A mixed method, concurrent nested
      design was used. Participants in the treatment group used the guided imagery
      technique over a consecutive 4-day period, and those in the control group were
      monitored. Verbal descriptions of pain were obtained before randomization and at
      four daily intervals. A total of 210 pain descriptions were obtained across the
      five time points. Data were analyzed using content analysis. Six categories
      emerged from the data: pain is never-ending, pain is relative, pain is
      explainable, pain is torment, pain is restrictive, and pain is changeable. For
      participants in the treatment group, pain became changeable. The meaning of pain
      as never-ending was a prominent theme for participants before randomization to
      treatment and control groups. It remained a strong theme for participants in the
      control group throughout the 4-day study period; however, pain as never-ending
      did not resurface for participants in the treatment group.

PMID- 15970920
TI  - Nursing staff members' assessments of pain in cognitively impaired nursing home
      residents.
AB  - Our aim was to assess the reliability and validity of nursing staff members'
      assessments of pain in cognitively impaired nursing home residents. Participants
      were 57 cognitively impaired nursing home residents and 52 nursing staff members.
      Twenty-eight residents had mild/moderate cognitive impairment and 29 were
      severely impaired. Nursing staff members were asked to evaluate their patients'
      pain using 2 scales: the Nurse Global Scale of pain (NGS) and the Present Pain
      Inventory (PPI). Independent measures of pain were obtained from patient
      interviews, physician assessments, and from the Minimum Data Set (MDS) items;
      these were used to measure validity of the nursing staff's perception of pain.
      Test-retest and inter-rater reliabilities were also computed. Significant
      correlations were obtained between most of the physician-derived measures and the
      PPI for the moderately impaired group, but not for the severely impaired group.
      Both measures of nursing assistants' pain assessments correlated significantly
      with MDS-based measures; these correlations were higher for the less cognitively
      impaired group. Finally, the PPI correlated significantly and positively with
      resident-derived measures for those with moderate rather than severe cognitive
      impairment. Nursing staff members' ratings of pain were correlated with
      residents' level of cognitive functioning and with intake of pain medication. The
      results underscore the difficulty in assessing pain in those with severe
      cognitive impairment.

PMID- 15970921
TI  - A description of a brief multidisciplinary treatment program for fibromyalgia.
AB  - The majority of fibromyalgia treatment programs are weeks or months in duration.
      This tertiary care center draws people worldwide for diagnostic purposes;
      however, most patients are unable to stay for extended treatment. It was deemed
      important to offer a brief multidisciplinary fibromyalgia treatment program that
      provided fundamental education and established a foundation for self-management
      strategies. This article describes the components of a brief multidisciplinary
      program for fibromyalgia. Initial results indicate improvement in patient
      outcomes and in patient and physician satisfaction. Patients who complete any
      fibromyalgia program need to maintain a relationship with their primary care
      providers for ongoing care. Some patients may need a more comprehensive program
      because of their level of functional impairment.

PMID- 15970922
TI  - No association of breast cancer risk with integrin beta3 (ITGB3) Leu33Pro
      genotype.
AB  - To pursue a borderline increased risk of breast cancer for carriers of two
      integrin beta(3) (ITGB3) 33Pro alleles found in a recent prospective study, we
      conducted a case-control study of 1088 women with breast cancer and 4815 female
      controls. Leu33Pro heterozygotes, homozygotes and heterozygotes+homozygotes vs
      noncarriers had odds ratios for breast cancer of 1.0 (95% confidence interval:
      0.8-1.1), 0.8 (0.5-1.2) and 1.0 (0.8-1.1), respectively. After stratification for
      conventional risk factors, odds ratio for breast cancer in heterozygotes,
      homozygotes and heterozygotes+homozygotes vs noncarriers were not increased above
      1.0 in any of the 14 strata examined. This was also true after stratification for
      tumour histological subtype and cancer stage at the time of diagnosis.

PMID- 15970923
TI  - The endothelin B (ETB) receptor agonist IRL 1620 is highly vasoconstrictive in
      two syngeneic rat tumour lines: potential for selective tumour blood flow
      modification.
AB  - The vascular effects of the endothelin B (ET(B)) receptor agonist IRL 1620 were
      investigated in the rat P22 carcinosarcoma and a range of normal tissues in BDIX
      rats. Tissue blood flow rate was calculated from measurements of tissue uptake of
      radiolabelled iodoantipyrine. A comparison of vascular effects in the P22 tumour
      and the HSN sarcoma growing in CBH/CBi rats was made using laser Doppler
      flowmetry, showing similar effects of IRL 1620, with red cell flux rapidly
      decreasing by 50-60% and then returning to control levels within approximately 30
      min. This corresponded to similar levels but different spatial organisation of
      ET(B) binding sites in the two tumours, as measured by autoradiography. The
      decrease in tumour blood flow and an increase in vascular resistance suggest that
      the vascular component of ET(B) receptors in the P22 tumour is localised on
      contractile elements rather than on endothelial cells. ET(A) receptors were also
      identified. Vasoconstriction occurred uniformly throughout the P22 tumour mass,
      consistent with a measured homogeneous distribution of ET(B) receptors. IRL 1620
      caused vasoconstriction in normal skeletal muscle, kidney and small intestine of
      the BDIX rat as well as in tumour, but did not affect blood flow in other
      tissues. These effects could be useful for limiting toxicity of certain
      chemotherapeutic agents. Fully functional ET(B) receptors are clearly expressed
      on tumour vasculature and IRL 1620 shows promise for short-term modification of
      tumour blood flow. Expression levels of ET(B) receptors on the tumour vasculature
      could be useful for predicting which tumours are likely to respond to IRL 1620.

PMID- 15970924
TI  - Monoclonal antibody A7-superparamagnetic iron oxide as contrast agent of MR
      imaging of rectal carcinoma.
AB  - Superparamagnetic iron oxide (SPIO)-based colloid has been used clinically as a
      tissue-specific magnetic resonance contrast agent. We coupled monoclonal antibody
      A7 (Mab A7), which reacts specifically with human colorectal carcinoma, to
      Ferumoxides (SPIO) and examined the accumulation of this conjugate in xenografted
      tumours in nude mice. We examined in vitro immunoreactivity of Mab A7 coupled to
      Ferumoxides and its in vivo distribution in nude mice with human colorectal
      carcinoma. Magnetic resonance imaging of tumour-bearing nude mice was performed
      72 h after injection of A7-Ferumoxides. A7-Ferumoxides retained binding
      activities that were nearly identical to intact Mab A7. More of the radiolabelled
      A7-Ferumoxides accumulated in the tumour than normal mouse IgG-Ferumoxides from
      12 h onwards after injection (P<0.05). Both A7-Ferumoxides and normal mouse IgG
      Ferumoxides disappeared from blood linearly over time. The accumulation levels in
      normal tissue decreased linearly over time but were lower than levels in tumours
      from 6 h. In magnetic resonance T2-weighted imaging of the tumour-bearing nude
      mice, signal intensity was reduced at the margin of the tumour by injection of A7
      Ferumoxides. Mab A7 coupled to Ferumoxides is potentially suitable as a magnetic
      resonance contrast agent for detecting local recurrence of rectal carcinoma.

PMID- 15970925
TI  - Mutations in Rb1 pathway-related genes are associated with poor prognosis in
      anaplastic astrocytomas.
AB  - Anaplastic astrocytoma (AA, WHO grade III) is, second to Glioblastoma, the most
      common and most malignant type of adult CNS tumour. Since survival for patients
      with AA varies markedly and there are no known useful prognostic or therapy
      response indicators, the primary purpose of this study was to examine whether
      knowledge of the known genetic abnormalities found in AA had any clinical value.
      The survival data on 37 carefully sampled AA was correlated with the results of a
      detailed analysis of the status of nine genes known to be involved in the
      development of astrocytic tumours. These included three genes coding for proteins
      in the p53 pathway (TP53, p14(ARF)and MDM2), four in the Rb1 pathway (CDKN2A,
      CDKN2B, RB1 and CDK4) and PTEN and EGFR. We found that loss of both wild-type
      copies of any of the three tumour suppressor genes CDKN2A, CDKN2B and RB1 or gene
      amplification of CDK4, disrupting the Rb1 pathway, were associated with shorter
      survival (P=0.009). This association was consistent in multivariate analysis,
      including adjustment for age (P=0.013). The findings suggest that analysis of the
      genes coding for Rb1 pathway components provides additional prognostic
      information in AA patients receiving conventional therapy.

PMID- 15970926
TI  - HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant
      chemotherapy in breast cancer patients.
AB  - No data are available on the role of HER2 overexpression in predicting the
      efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast
      cancer patients. We retrospectively evaluated this role in patients enrolled in a
      phase III study comparing standard FEC21 (5-fluorouracil, epirubicin, and
      cyclophosphamide, administered every 3 weeks) vs dose-dense FEC14 (the same
      regimen repeated every 2 weeks). HER2 status was determined for 731 of 1214
      patients. Statistical analyses were performed to test for interaction between
      treatment and HER2 status with respect to event-free survival (EFS) and overall
      survival (OS); EFS and OS were compared within each HER2 subgroup and within each
      treatment arm. Median follow-up was 6.7 years. Among FEC21-treated patients, both
      EFS (HR=2.07; 95% CI 1.27-3.38) and OS (HR=2.47; 95% CI 1.34-4.57) were
      significantly worse in HER2 + patients than in HER2 - patients. Among FEC14
      treated patients, differences in either EFS (HR=1.21; 95% CI 0.65-2.24) or OS
      (HR=1.85; 95% CI 0.88-3.89) between HER2 + and HER2 - patients were not
      statistically significant. Interaction analysis suggested that the use of dose
      dense FEC14 might remove the negative prognostic effect of HER2 overexpression on
      EFS and OS. Our data suggest a potential role of HER-2 overexpression in
      predicting the efficacy of dose-dense epirubicin-containing chemotherapy and the
      need to confirm this hypothesis in future prospective studies.

PMID- 15970927
TI  - Second primary cancers among 109 000 cases of non-Hodgkin's lymphoma.
AB  - An analysis of other primary cancers in individuals with non-Hodgkin's lymphoma
      (NHL) can help to elucidate this cancer aetiology. In all, 109 451 first primary
      NHL were included in a pooled analysis of 13 cancer registries. The observed
      numbers of second cancers were compared to the expected numbers derived from the
      age-, sex-, calendar period- and registry-specific incidence rates. We also
      calculated the standardised incidence ratios for NHL as a second primary after
      other cancers. There was a 47% (95% confidence interval 43-51%) overall increase
      in the risk of a primary cancer after NHL. A strongly significant (P<0.001)
      increase was observed for cancers of the lip, tongue, oropharynx*, stomach, small
      intestine, colon*, liver, nasal cavity*, lung, soft tissues*, skin melanoma*,
      nonmelanoma skin*, bladder*, kidney*, thyroid*, Hodgkin's lymphoma*, lymphoid
      leukaemia* and myeloid leukaemia. Non-Hodgkin's lymphoma as a second primary was
      increased after cancers marked with an asterisk. Patterns of risk indicate a
      treatment effect for lung, bladder, stomach, Hodgkin's lymphoma and myeloid
      leukaemia. Common risk factors may be involved for cancers of the lung, bladder,
      nasal cavity and for soft tissues, such as pesticides. Bidirectional effects for
      several cancer sites of potential viral origin argue strongly for a role for
      immune suppression in NHL.

PMID- 15970929
TI  - The BDNF Val66Met polymorphism is not associated with late onset Alzheimer's
      disease in three case-control samples.

PMID- 15970928
TI  - Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma
      cells.
AB  - Multiple myeloma (MM) accounts for 1 % of all cancer deaths. Although treated
      aggressively, almost all myelomas eventually recur and become resistant to
      treatment. Atiprimod (2-(3-Diethylaminopropyl)-8,8-dipropyl-2-azaspiro[4,5]
      decane dimaleate) has exerted anti-inflammatory activities and inhibited
      oeteoclast-induced bone resorption in animal models and been well tolerated in
      patients with rheumatoid arthritis in phase I clinical trials. Therefore, we
      investigated its activity in MM cells and its mechanism of action. We found that
      Atiprimod inhibited proliferation of the myeloma cell lines U266-B1, OCI-MY5, MM
      1, and MM-1R in a time- and dose-dependent manner. Atiprimod blocked U266-B1
      myeloma cells in the G(0)/G(1) phase, preventing cell cycle progression.
      Furthermore, Atiprimod inhibited signal transducer and activator of transcription
      (STAT) 3 activation, blocking the signalling pathway of interleukin-6, which
      contributes to myeloma cell proliferation and survival, and downregulated the
      antiapoptotic proteins Bcl-2, Bcl-X(L), and Mcl-1. Incubation of U266-B1 myeloma
      cells with Atiprimod induced apoptosis through the activation of caspase 3 and
      subsequent cleavage of the DNA repair enzyme poly(adenosine diphosphate-ribose)
      polymerase. Finally, Atiprimod suppressed myeloma colony-forming cell
      proliferation in fresh marrow cells from five patients with newly diagnosed MM in
      a dose-dependent fashion. These data suggest that Atiprimod has a role in future
      therapies for MM.

PMID- 15970930
TI  - The phenotypes of bipolar disorder: relevance for genetic investigations.
AB  - The search for susceptibility genes for bipolar disorder (BD) depends on
      appropriate definitions of the phenotype. In this paper, we review data on
      diagnosis and clinical features of BD that could be used in genetic studies to
      better characterize patients or to define homogeneous subgroups. Clinical
      symptoms, long-term course, comorbid conditions, and response to prophylactic
      treatment may define groups associated with more or less specific loci. One such
      group is characterized by symptoms of psychosis and linkage to 13q and 22q. A
      second group includes mainly bipolar II patients with comorbid panic disorder,
      rapid mood switching, and evidence of chromosome 18 linkage. A third group
      comprises typical BD with an episodic course and favourable response to lithium
      prophylaxis. Reproducibility of cognitive deficits across studies raises the
      possibility of using cognitive profiles as endophenotypes of BD, with deficits in
      verbal explicit memory and executive function commonly reported. Brain imaging
      provides a more ambiguous data set consistent with heterogeneity of the illness.

PMID- 15970931
TI  - Immunology. All of it.

PMID- 15970932
TI  - Paul Ehrlich, archives and the history of immunology.

PMID- 15970933
TI  - Notch in lymphopoiesis and T cell polarization.

PMID- 15970934
TI  - Affecting the effectors: a kick in the gut?

PMID- 15970935
TI  - Type I interferon and cancer immunoediting.

PMID- 15970937
TI  - Invertebrate immunity and the limits of mechanistic immunology.
AB  - Rapid progress is being made in elucidating the molecular mechanisms involved in
      invertebrate immunity. This search for molecules runs the risk of missing
      important phenomena. In vertebrates, acquired protection and pathogen-specific
      responses were demonstrated experimentally long before the mechanisms responsible
      were elucidated. Without analogous experiments, mechanism-driven work may not
      demonstrate the full richness of invertebrate immunity.

PMID- 15970938
TI  - AID to overcome the limitations of genomic information.
AB  - The limitations of genomic information forced our ancestors to adopt a strategy
      for introducing somatic DNA alterations with the risk of genome instability.
      Although activation-induced deaminase (AID) is involved in DNA cleavage in
      somatic hypermutation and class-switch recombination, its mechanism of action has
      been debated extensively, with the two main hypotheses being distinguished by the
      chief target of AID: RNA or DNA. The principle distinction between the two
      hypotheses is the requirement for translation of edited mRNA or uracil removal
      from DNA for DNA cleavage. Although a series of experiments has provided support
      for the 'RNA-editing' hypothesis and requires reevaluation of the 'DNA
      deamination' hypothesis, definitive proof is yet to come.

PMID- 15970940
TI  - Feeding practice among younger Tibetan children living at high altitudes.
AB  - OBJECTIVE: Few published data are available on the feeding practice of younger
      children in Tibet. Our study investigated feeding pattern of younger Tibetan
      children. DESIGN AND SUBJECTS: The study was a cross-sectional survey conducted
      in Tibet. A sample of 1655 children younger than 36 months old and their mothers
      was obtained by stratified multistage cluster random sampling method. Mothers
      were interviewed to collect information on feeding practice by a designed family
      questionnaire including initial time and duration of breastfeeding and time,
      frequency and types of complementary foods introduced. RESULTS: Most of the
      children was ever or being breastfed at the time of interview. The median
      duration of breastfeeding was 26 months. The prevalence of almost exclusive
      breastfeeding for 4 months was 20.1%. Mothers' age and education, child's
      residence, and introduction of egg, fresh milk and milk powder were strongly
      associated with the duration of breastfeeding. The partial feeding was a main
      pattern in the first 6 months of life. Zanban and porridge were offered at about
      1 month after birth. By 6th month, less than 25% of children were fed protein
      foods such as egg and meats and only near 20% of children were fed fresh
      vegetables. Bean products, fish and chicken were seldom offered to children.
      CONCLUSIONS: We conclude that although they were breastfed for long time,
      complementary feeding practice of Tibetan children was disadvantaged, especially
      of rural children. Improvement of monotonous complementary foods and timely
      introduction should be stressed in local programmatic nutritional interventions.

PMID- 15970941
TI  - Obesity, overweight and thinness in schoolchildren of the city of Florianopolis,
      Southern Brazil.
AB  - OBJECTIVE: To assess the prevalence of obesity, overweight (including obesity)
      and thinness in children of the city of Florianopolis (southern Brazil). DESIGN:
      Cross-sectional study. SUBJECTS: Representative sample of 7-10-y-old
      schoolchildren of the first four grades of elementary schools (1432 girls, 1504
      boys). METHODS: Measurements of weight, height and triceps skinfold thickness
      (TSF) were taken following standard techniques. The body mass index (BMI) was
      computed as weight/height2. Nutritional status was defined using two references:
      (1) the Must et al reference for BMI and TSF to define thinness, overweight and
      obesity (5th, 85th and 95th percentiles, respectively); (2) the International
      Obesity Task Force (IOTF) BMI cutoffs to define overweight and obesity. RESULTS:
      Using BMI, according to the Must et al, and IOTF references, the prevalence of
      obesity was 10.6 and 5.5%, respectively; overweight (including obesity) affected
      26.2 and 22.1% of children, respectively. According to the Must et al reference,
      the prevalence of thinness was 3.2%. Using TSF rather than BMI, according to the
      Must et al references, fewer children were classified as obese (8.0%) or
      overweight (20.2%) and more children were classified as thin (4.9%). CONCLUSION:
      This study supports the previously reported high frequencies of childhood
      overweight and obesity in developing countries. The data allow comparisons with
      other studies carried out in Brazil and other parts of the world.

PMID- 15970942
TI  - Excess male chronic energy deficiency among adolescents: a cross-sectional study
      in the context of patrilineal and matrilineal societies in Northeast India.
AB  - OBJECTIVE: To determine the sex differences in chronic energy deficiency (CED)
      among adolescents in the context of patrilineal and matrilineal societies in
      Northeast India. DESIGN: Cross-sectional, community-based study of the Hmar
      patrilineal society and the Khasi (War and Khynriam) matrilineal society.
      SETTING: Mizoram and Meghalaya in Northeast India. SUBJECTS: In total, 1733
      adolescent boys and girls aged 9-16 y: Khynriam Khasis (n = 1005), War Khasis (n
      = 305) and Hmars (n = 423). MEASUREMENTS: Weight, height, and socio-economic
      characteristics. Body mass index (weight in kg/height in m2) was used for
      assessing CED relative to the international reference values. RESULTS: The
      overall prevalence of CED was significantly greater in boys than in girls. The
      sex differences in the prevalence of CED were 5, 10 and 6% points in the Khynriam
      Khasis, War Khasis and Hmars, respectively. Allowing for age and socio-economic
      variables, the risks of CED were about 1.82 (95% CI 1.14-2.90), 1.83 (95% CI 1.19
      3.33) and 1.78 (95% CI 1.10-3.25) times greater in boys than in girls among the
      Khynriam Khasis, War Khasis and Hmars, respectively. Using logistic regression
      analysis, the prevalence of CED was negatively associated with family income
      across study populations. No significant association was found between CED and
      religion. CONCLUSION: Patrilineal and matrilineal forms of society were not
      reflected in the prevalence of CED among adolescents. Subject to further studies
      of the research problems concerning the nutritional status of adolescents, girls
      fare better than boys with respect to the prevalence of CED.

PMID- 15970943
TI  - A shift in the epidemiology of low body mass index in Brazilian adults.
AB  - OBJECTIVE: To study the prevalence and current predictors of low body mass index
      (BMI) in a population undergoing a rapid nutritional transition. DESIGN:
      Population-based cross-sectional study. SETTINGS: Individuals living in the urban
      area of Pelotas, a medium-sized southern Brazilian city, were interviewed at
      home. SUBJECTS: A multiple-stage sampling strategy was used. Out of 3372 eligible
      subjects, 3047 were interviewed. The study was restricted to adults (> or = 20
      y). MAIN OUTCOME MEASURE: Low BMI was defined as <18.5 kg/m2. RESULTS: The
      prevalence of low BMI was 2.7% (95% confidence interval: 2.1; 3.3), higher in
      women than men (3.8 vs 1.3%; P < 0.001). In the whole sample (men and women
      combined), living without a partner and current smoking were positively
      associated with low BMI. Among women, low BMI presented a U-shaped relationship
      with age and was positively associated with educational level. The prevalence of
      low BMI in young women was 6.3%, and in highly educated young women was 8.9%.
      CONCLUSIONS: Consistently with previous Brazilian studies, a decline in the
      overall prevalence of low BMI is clear. However, differently from these studies,
      the predictors of low BMI in women are similar to those observed within developed
      countries (including low age and high education), possibly indicating an increase
      in eating disorders.

PMID- 15970944
TI  - Genomic effect of vitamin 'C' and statins within human mononuclear cells involved
      in atherogenic process.
AB  - Deregulated crosstalk within nuclear receptor/transcription factor family,
      comprising of peroxisome proliferator-activated receptors (PPARs) and liver X
      receptor-alpha (LXR-alpha), can give rise to cooperativity between lipid
      peroxidation and inflammation leading to atherogenic process. The present study
      addressed to explore the effect of statins and vitamin 'C' on transcriptional
      expression of genes coding for this nuclear receptor/transcription factor family
      within mononuclear cells revealed for the first time that both mevastatin and
      vitamin 'C' have common action in that they significantly downregulate the
      expression of PPARs (alpha, gamma) genes and upregulate LXR-alpha gene expression
      as compared to the control. The similar phenomenon was observed in mononuclear
      cells obtained from coronary heart disease (CHD) patients who were receiving
      atorvastatin treatment (20 mg HS). Further, the observed upregulatory effect of
      LXR-alpha gene expression was in conformity with the downregulatory effect of LXR
      alpha on its effector gene matrix metalloproteinase-9. Based on these results, we
      propose that LXR-alpha-dependent signaling pathway may be a crucial target for
      the therapeutic intervention in human CHD, and in addition to statins, vitamin
      'C' deserves a close scrutiny for the treatment of CHD.

PMID- 15970945
TI  - Interdevice variability in percent fat estimates using the BOD POD.
AB  - OBJECTIVE: To evaluate interdevice reliability in body density (Db) and percent
      body fat (%BF) using air-displacement plethysmography, the BOD POD (BP) body
      composition system. DESIGN AND SETTING: Duplicate body composition tests were
      performed in immediate succession on 50 adults (26 M, 24 F; 21-53 y) using two BP
      units located in the same body composition laboratory. RESULTS: Mean Db and %BF
      between BP1 and BP2 did not differ significantly for men (DeltaDb = 0.0003+/
      0.0008 g/ml, P = 0.632; Delta%BF = 0.1+/-1.3, P = 0.665), while for women, there
      were small but significant differences in Db and %BF between BP1 and BP2 (DeltaDb
      = 0.0018+/-0.0003 g/ml, P = 0.001; Delta%BF = 0.8+/-1.1, P = 0.001). The
      regression between %BF by BP1 and BP2 did not deviate significantly from the line
      of identity for both men and women (R2 = 0.95, standard error of estimate
      (s.e.e.) = 1.23 %BF for men; R2 = 0.97, s.e.e = 1.13 %BF for women). Individual
      variations in %BF estimates between the two BP units were within acceptable
      ranges (95% limits of agreement = -2.5-2.7 %BF for men; -1.4-3.0 %BF for women),
      and there was no trend in individual differences as %BF varied (r = -0.19, P =
      0.359 for men; r = 0.09, P = 0.677 for women). Other subject characteristics,
      including age, body mass, height, and body mass index, did not significantly
      contribute to the differences in %BF estimates by the two BP units. CONCLUSIONS:
      No clinically significant differences in Db and %BF estimates exist between the
      BP units, and the interdevice variability of the BP has minimal impact on %BF
      estimates. Further, test-to-test reliability between BP units appears to be as
      good as within one unit.

PMID- 15970946
TI  - Little effect of physical training on body composition and nutritional intake
      following colorectal surgery--a randomised placebo-controlled trial.
AB  - OBJECTIVE: Postoperatively patients have a reduction in nutritional intake and
      body weight. We studied the effect of postoperative physical training on
      nutritional intake and body composition. METHODS: Patients > or =60 y admitted
      for elective colorectal surgery were randomised to train muscular strength (group
      A) or to nonstrengthening exercises (group B) for 3 months. Fat mass (FM) and
      lean body mass (LBM) were assessed with bioimpedance preoperatively, 7, 30, and
      90 days postoperatively. Nutritional intake was registered in a subpopulation.
      RESULTS: Of 119 included patients, 60 were randomised to group A and 59 to B. The
      changes in LBM at postoperative day 7 were a mean (s.d.) of 0.4 (2.1) kg in group
      A compared to -0.7 (2.0) kg in B. The difference between groups of 1.2 (0.5) kg
      at day 7 was statistically significant (P=0.03). At no other time was observed
      difference between groups in weight, LBM, or FM. The energy and protein intake
      rose during postoperative day 1-7 and rose further after discharge. At no time
      were differences between groups. CONCLUSION: Physical training had little effect
      on body composition following abdominal surgery. The nutritional intake in well
      nourished patients did not increase by training.

PMID- 15970947
TI  - Differential effects of two chronic diazepam treatment regimes on withdrawal
      anxiety and AMPA receptor characteristics.
AB  - Withdrawal from chronic benzodiazepines is associated with increased anxiety and
      seizure susceptibility. Neuroadaptive changes in neural activity occur in limbo
      cortical structures although changes at the level of the GABA(A) receptor do not
      provide an adequate explanation for these functional changes. We have employed
      two diazepam treatment regimes known to produce differing effects on withdrawal
      aversion in the rat and examined whether withdrawal-induced anxiety was
      accompanied by changes in AMPA receptor characteristics. Rats were given 28 days
      treatment with diazepam by the intraperitoneal (i.p.) route (5 mg/kg) and the
      subcutaneous (s.c.) route (15 mg/kg). Withdrawal anxiety in the elevated plus
      maze was evident in the group withdrawn from chronic s.c. diazepam (relatively
      more stable plasma levels) but not from the chronic i.p. group (fluctuating daily
      plasma levels). In the brains of these rats, withdrawal anxiety was accompanied
      by increased [3H]Ro48 8587 binding in the hippocampus and thalamus, and decreased
      GluR1 and GluR2 subunit mRNA expression in the amygdala (GluR1 and GluR2) and
      cortex (GluR1). The pattern of changes was different in the chronic i.p. group
      where in contrast to the chronic s.c. group, there was reduced [3H]Ro48 8587
      binding in the hippocampus and no alterations in GluR1 and GluR2 subunit
      expression in the amygdala. While both groups showed reduced GluR1 mRNA subunit
      expression in the cortex overall, only the agranular insular cortex exhibited
      marked reductions following chronic i.p. diazepam. Striatal GluR2 mRNA expression
      was increased in the i.p. group but not the s.c. group. Taken together, these
      data are consistent with differential neuroadaptive processes in AMPA receptor
      plasticity being important in withdrawal from chronic benzodiazepines. Moreover,
      these processes may differ both at a regional and receptor function level
      according to the behavioral manifestations of withdrawal.

PMID- 15970948
TI  - Alterations of interneurons of the gerbil hippocampus after transient cerebral
      ischemia: effect of pitavastatin.
AB  - We investigated the immunohistochemical alterations of parvalbumin (PV)
      expressing interneurons in the hippocampus after transient cerebral ischemia in
      gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing
      interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase inhibitor pitavastatin against the damage of neurons and interneurons
      in the hippocampus after cerebral ischemia. Severe neuronal damage was observed
      in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV
      immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days
      after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was
      observed in interneurons of the hippocampal CA1 sector. Furthermore, a
      significant decrease of PV immunoreactivity was found in interneurons of the
      hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was
      detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a
      decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1
      sector up to 14 days after ischemia. Pitavastatin significantly prevented the
      neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our
      immunohistochemical study also showed that pitavastatin prevented significant
      decrease of PV- and nNOS-positive interneurons in the hippocampus after ischemia.
      Double-labeled immunostainings showed that PV immunoreactivity was not found in
      nNOS-immunopositive interneurons of the brain. The present study demonstrates
      that cerebral ischemia can cause a loss of both PV- and nNOS-immunoreactive
      interneurons in the hippocampal CA1 sector. Our findings also show that the
      damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in
      the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play
      some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our
      present study indicates that pitavastatin can prevent the damage of interneurons
      in the hippocampus after cerebral ischemia. Thus, our study provides valuable
      information for the pathogenesis after cerebral ischemia.

PMID- 15970949
TI  - The amazing complexity of the human transcriptome.

PMID- 15970950
TI  - PINK1, Parkin, and DJ-1 mutations in Italian patients with early-onset
      parkinsonism.
AB  - Recessively inherited early-onset parkinsonism (EOP) has been associated with
      mutations in the Parkin, DJ-1, and PINK1 genes. We studied the prevalence of
      mutations in all three genes in 65 Italian patients (mean age of onset: 43.2+/
      5.4 years, 62 sporadic, three familial), selected by age at onset equal or
      younger than 51 years. Clinical features were compatible with idiopathic
      Parkinson's disease in all cases. To detect small sequence alterations in Parkin,
      DJ-1, and PINK1, we performed a conventional mutational analysis
      (SSCP/dHPLC/sequencing) of all coding exons of these genes. To test for the
      presence of exon rearrangements in PINK1, we established a new quantitative
      duplex PCR assay. Gene dosage alterations in Parkin and DJ-1 were excluded using
      previously reported protocols. Five patients (8%; one woman/four men; mean age at
      onset: 38.2+/-9.7 (range 25-49) years) carried mutations in one of the genes
      studied: three cases had novel PINK1 mutations, one of which occurred twice
      (homozygous c.1602_1603insCAA; heterozygous c.1602_1603insCAA; heterozygous
      c.836G>A), and two patients had known Parkin mutations (heterozygous c.734A>T and
      c.924C>T; heterozygous c.924C>T). Family history was negative for all mutation
      carriers, but one with a history of tremor. Additionally, we detected one novel
      polymorphism (c.344A>T) and four novel PINK1 changes of unknown pathogenic
      significance (-21G/A; IVS1+97A/G; IVS3+38_40delTTT; c.852C>T), but no exon
      rearrangements. No mutations were found in the DJ-1 gene. The number of mutation
      carriers in both the Parkin and the PINK1 gene in our cohort is low but
      comparable, suggesting that PINK1 has to be considered in EOP.

PMID- 15970951
TI  - Research Training for Clinicians: The Crucial Link Between Evidence-Based
      Practice and Third-Party Reimbursement.

PMID- 15970952
TI  - Influence of Hydration and Electrolyte Supplementation on Incidence and Time to
      Onset of Exercise-Associated Muscle Cramps.
AB  - Context: Exercise-associated muscle cramps (EAMCs) are common among physically
      active individuals and are temporarily disabling; therefore, prevention is of
      great interest.Objective: To determine the role of hydration and electrolyte
      supplementation in the prevention of EAMCs.Design: Each subject completed 2
      counterbalanced trials in a repeated-measures design.Setting: University of
      Alabama.Patients or Other Participants: College-aged men (n = 13) with a history
      of EAMCs.Intervention(s): In each trial, participants performed a calf-fatiguing
      protocol to induce EAMCs in the calf muscle group. Each trial was performed in a
      hot environment (dry bulb temperature of 37 degrees C, relative humidity of 60%).
      In the carbohydrate-electrolyte trial, subjects consumed, at a rate similar to
      sweat loss, a carbohydrate-electrolyte beverage with sodium chloride added. In
      the hypohydration trial, subjects were not allowed to consume any fluids.Main
      Outcome Measure(s): We measured the incidence and time to onset of EAMCs.Results:
      Nine participants experienced cramps in the carbohydrate-electrolyte trial,
      compared with 7 in the hypohydration trial. Of the 7 individuals who had EAMCs in
      both trials, exercise duration before onset was more than doubled in the
      carbohydrate-electrolyte trial (36.8 +/- 17.3 minutes) compared with the
      hypohydration trial (14.6 +/- 5.0 minutes, P < .01).Conclusions: Consumption of a
      carbohydrate-electrolyte beverage before and during exercise in a hot environment
      may delay the onset of EAMCs, thereby allowing participants to exercise longer.
      However, it appears that dehydration and electrolyte loss are not the sole causes
      of EAMCs, because 69% of the subjects experienced EAMCs when they were hydrated
      and supplemented with electrolytes.

PMID- 15970953
TI  - Cluster-Randomized Controlled Trial of An Athletic Trainer-Directed Spit
      (Smokeless) Tobacco Intervention for Collegiate Baseball Athletes: Results After
      1 Year.
AB  - Context: Athletes in the United States are at high risk for using spit
      (smokeless) tobacco (ST) and incurring its associated adverse health
      effects.Objective: To examine whether an athletic trainer-directed ST
      intervention could decrease initiation and promote cessation of ST use among male
      collegiate baseball athletes.Design: Stratified, cluster-randomized controlled
      trial.Setting: Fifty-two California colleges.Patients or Other Participant(s): A
      total of 883 subjects in 27 intervention colleges and 702 subjects in 25 control
      colleges participated, as did 48 certified athletic trainers.Intervention(s): For
      college athletic trainers and associated dental professionals, a 3-hour video
      conference, and for collegiate athletes, an oral cancer screening with feedback
      and brief counseling during the preseason health screenings, athletic trainer
      support for cessation, and a peer-led educational baseball team meeting.Main
      Outcome Measure(s): The subjects' ST use over 1 year was assessed by self-report.
      At the end of the study, the certified athletic trainers were mailed a survey
      assessing their tobacco use and perceptions and behavior related to tobacco
      control in the athletic environment. We used multivariable logistic regression
      models for clustered responses (generalized estimating equations) to test the
      difference between groups in ST-use initiation and cessation and to identify
      significant overall predictors of noninitiation and cessation of ST use.Results:
      Of the 1585 athletes recruited, 1248 (78.7%) were followed up at 12 months. In
      addition, 48 of the 52 athletic trainers (92%) responded to the 1-year follow-up
      survey. The ST-use initiation (incidence) was 5.1% in intervention colleges and
      8.4% in control colleges (generalized estimating equation odds ratio = 0.58, 95%
      confidence interval = 0.35-0.99). Predictors of ST noninitiation were low
      lifetime tobacco and monthly alcohol use (odds ratio = 1.98, 95% confidence
      interval = 1.40- 2.82) and athletic trainers' report that the baseball coach
      supported ST-use prevention activities (odds ratio = 1.43, 95% confidence
      interval = 1.11-1.83). Although at 1 year, cessation of ST use was relatively
      high in both groups (36%), we noted no significant difference between the groups
      (odd ratio = 0.94, 95% confidence interval = 0.70-1.27).Conclusions: The
      intervention was significantly effective in preventing incident ST use but did
      not significantly increase cessation beyond that seen in the control group. The
      latter finding is inconsistent with previous studies and may be explained by
      spillover of the intervention to control colleges, other anti-tobacco activity in
      control colleges, and/or the small sample of dependent ST users enrolled in the
      study.

PMID- 15970954
TI  - The Short-Term Effects of Joint Mobilizations on Acute Mechanical Low Back
      Dysfunction in Collegiate Athletes.
AB  - Context: Although a variety of theories and studies have been cited to support
      the use of joint mobilization in the spine as an integral part of the treatment
      and rehabilitation process, information about the short-term effects of joint
      mobilization on acute low back injury with respect to patient pain and strength
      changes has been limited.Objective: To examine the short-term effects of grade 1
      and 2 posteroanterior joint mobilizations at the lumbar spine on subject pain and
      muscle force after an episode of acute, mechanical low back pain.Design: Group
      (2) by time (2 or 3).Setting: Athletic training clinic.Patients or Other
      Participants: Male collegiate athletes (n = 19) with mechanical low back pain as
      assessed through a standardized evaluation were randomly assigned to a control (n
      = 10) or experimental (n = 9) group.Intervention(s): All subjects underwent a
      standardized treatment protocol of cryotherapy and stretching during data
      collection. Subjects completed the McGill Pain Questionnaire and a visual analog
      scale (the latter to assess pain levels during range-of-motion activities) and,
      using a handheld dynamometer, performed 3 maximum voluntary isometric
      contractions to determine muscle force. Grade 1 and 2 joint mobilizations were
      administered to the experimental group, whereas the control group was placed in a
      prone position of comfort for the time it took to perform the joint
      mobilizations.Main Outcome Measure(s): Baseline, immediate posttreatment, and 24
      hour posttreatment measurements of pain and muscle force were taken.Results:
      Compared with the control group, the experimental group demonstrated significant
      decreases in the sensory subscale scores of the McGill Pain Questionnaire and in
      pain during lumbar extension and a significant increase in force
      production.Conclusions: Grade 1 and 2 joint mobilizations reduced subjects' pain
      and increased force production in the short-term stages of mechanical low back
      pain.

PMID- 15970955
TI  - Acute Effects of Static and Proprioceptive Neuromuscular Facilitation Stretching
      on Muscle Strength and Power Output.
AB  - Context: Stretching is commonly used as a technique for injury prevention in the
      clinical setting. Our findings may improve the understanding of the neuromuscular
      responses to stretching and help clinicians make decisions for rehabilitation
      progression and return to play.Objective: To examine the short-term effects of
      static and proprioceptive neuromuscular facilitation stretching on peak torque
      (PT), mean power output (MP), active range of motion (AROM), passive range of
      motion (PROM), electromyographic (EMG) amplitude, and mechanomyographic (MMG)
      amplitude of the vastus lateralis and rectus femoris muscles during voluntary
      maximal concentric isokinetic leg extensions at 60 and 300 degrees .s.Design: A
      randomized, counterbalanced, cross-sectional, repeated-measures design.Setting: A
      university human research laboratory.Patients or Other Participants: Ten female
      (age, 23 +/- 3 years) and 9 male (age, 21 +/- 3 years) apparently healthy and
      recreationally active volunteers.Intervention(s): Four static or proprioceptive
      neuromuscular facilitation stretching exercises to stretch the leg extensor
      muscles of the dominant limb during 2 separate, randomly ordered laboratory
      visits.Main Outcome Measure(s): The PT and MP were measured at 60 and 300 degrees
      .s, EMG and MMG signals were recorded, and AROM and PROM were measured at the
      knee joint before and after the stretching exercises.Results: Static and
      proprioceptive neuromuscular facilitation stretching reduced PT (P = .051), MP (P
      = .041), and EMG amplitude (P = .013) from prestretching to poststretching at 60
      and 300 degrees .s (P < .05). The AROM (P < .001) and PROM (P = .001) increased
      as a result of the static and proprioceptive neuromuscular facilitation
      stretching. The MMG amplitude increased in the rectus femoris muscle in response
      to the static stretching at 60 degrees .s (P = .031), but no other changes in MMG
      amplitude were observed (P > .05).Conclusions: Both static and proprioceptive
      neuromuscular facilitation stretching caused similar deficits in strength, power
      output, and muscle activation at both slow (60 degrees .s) and fast (300 degrees
      .s) velocities. The effect sizes, however, corresponding to these stretching
      induced changes were small, which suggests the need for practitioners to consider
      a risk-to-benefit ratio when incorporating static or proprioceptive neuromuscular
      facilitation stretching.

PMID- 15970956
TI  - Isokinetic Scapular Muscle Performance in Overhead Athletes With and Without
      Impingement Symptoms.
AB  - Context: Overhead activities such as throwing, tennis, or volleyball place
      athletes at considerable risk for overuse injuries. A relationship between
      scapulothoracic muscle imbalance and shoulder pain has been suggested.Objective:
      To compare the isokinetic muscle performance of the scapular muscles between
      overhead athletes with impingement symptoms and uninjured overhead athletes and
      to identify strength deficits in the patient population.Design: A repeated
      measures analysis of variance with 1 within-subjects factor (side) and 1 between
      subjects factor (group) was used to compare strength values and
      agonist:antagonist ratios across sides and across groups.Setting: University
      laboratory.Patients or Other Participants: Thirty overhead athletes with chronic
      shoulder impingement symptoms and 30 overhead athletes without a history of
      shoulder pain.Intervention(s): A linear protraction-retraction movement in the
      scapular plane at 2 velocities (12.2 cm/s and 36.6 cm/s).Main Outcome Measure(s):
      Isokinetic strength values and protraction:retraction ratios for both
      velocities.Results: Overhead athletes with impingement symptoms showed decreased
      force output:body weight at both velocities in the protractor muscles on the
      injured side compared with the uninjured side (-13.7% at slow velocity, -15.5% at
      high velocity) and compared with the control group at high velocity (-20.7%). On
      both sides, the patient group had significantly lower protraction:retraction
      ratios than the control group, measured at slow velocity (nondominant = -11%,
      dominant = -13.7%).Conclusions: Overhead athletes with impingement symptoms
      demonstrated strength deficits and muscular imbalance in the scapular muscles
      compared with uninjured athletes.

PMID- 15970957
TI  - Effects of Ibuprofen and High-Voltage Electric Stimulation on Acute Edema
      Formation After Blunt Trauma to Limbs of Rats.
AB  - Context: Ibuprofen is widely used to manage pain and inflammation after
      orthopaedic trauma, but its effect on acute swelling has not been investigated.
      Cathodal high-voltage pulsed current (CHVPC) at 120 pulses per second and 90% of
      visible motor threshold is known to curb edema formation after blunt trauma to
      the hind limbs of rats.Objective: To examine the effects of ibuprofen, continuous
      CHVPC, and simultaneous ibuprofen and CHVPC on acute edema formation after blunt
      trauma to the hind limbs of rats.Design: Randomized, parallel-group, repeated
      measures design.Setting: Laboratory animal facility.Participants: A total of 21 3
      month-old Zucker Lean rats (mass = 288 +/- 55 g) were studied.Intervention(s): We
      assessed the effects of ibuprofen, continuous CHVPC, and simultaneous ibuprofen
      and CHVPC on acute edema formation after blunt trauma to the hind limbs of
      rats.Main Outcome Measure(s): Limb volumes were measured immediately before and
      after trauma and every 30 minutes over the 4 hours of the experiment.Results:
      Volumes of treated limbs of all 3 experimental groups were smaller (P < .05) than
      those of untreated limbs, but no treatment was more effective than
      another.Conclusions: Ibuprofen, CHVPC, and simultaneous ibuprofen and CHVPC
      effectively curbed edema after blunt injury by roughly 50% relative to untreated
      but similarly injured control limbs of rats.

PMID- 15970958
TI  - Maxillofacial Fractures and Dental Trauma in a High School Soccer Goalkeeper: A
      Case Report.
AB  - Objective: To present the case of a 17-year-old male soccer goalkeeper who
      sustained maxillofacial fractures and dental trauma after being struck in the
      face by an opponent's knee.Background: Because of the nature of the sport and a
      lack of protective headgear, soccer players are at risk for sustaining
      maxillofacial trauma. Facial injuries can complicate the routine management of on
      field medical emergencies often encountered by certified athletic trainers. The
      appropriate management of maxillofacial trauma on the playing field may help to
      reduce both the immediate and long-term morbidity and mortality associated with
      these injuries.Differential Diagnosis: Lacerated superior labial artery,
      lacerated upper lip, dental fractures, maxillofacial fractures, orbital blowout
      fracture, closed head injury, cervical spine injury, cerebrovascular
      accident.Treatment: The athlete received immediate on-field medical care and was
      subsequently transported to the hospital, where diagnostic testing was performed
      and further treatment was provided. Hospital inpatient management included dental
      and plastic surgery. After discharge from the hospital, the athlete underwent
      several additional dental procedures, including gingival surgery and nonsurgical
      endodontic treatments. The fractures were followed closely to assure that
      adequate healing had occurred. The athlete did not return to soccer.Uniqueness:
      Certified athletic trainers need to be prepared for on-field medical emergencies.
      Bleeding associated with maxillofacial trauma can complicate basic medical
      interventions such as airway maintenance. Inappropriate on-field management may
      result in unnecessary morbidity and mortality for the injured athlete. Therefore,
      immediate recognition of the severity of the injury is needed in order to
      institute appropriate airway-management strategies.Conclusions: It is sometimes
      necessary to consider nonstandard methods of airway management in order to first
      address heavy bleeding that may be associated with facial trauma. Achieving
      hemostasis is essential in order to prevent potentially life-threatening
      complications related to hemorrhage, such as airway obstruction and hypovolemic
      shock.

PMID- 15970959
TI  - Slipping Rib Syndrome in a Collegiate Swimmer: A Case Report.
AB  - Objective: To present the unique case of a collegiate swimmer who experienced
      nearly 9 months of unresolved rib pain.Background: A 20-year-old collegiate
      swimmer was jumping up and down, warming up before a race, when she experienced
      pain in the area of her left lower rib cage. She completed the event and 2
      additional events that day with moderate discomfort. The athlete was evaluated by
      a certified athletic trainer 3 days postinjury and followed up over the next 9
      months with the team physician, a chiropractor, a nonsurgical sports medicine
      physician, and a thoracic surgeon.Differential Diagnosis: Intercostal strain,
      oblique strain, fractured rib, somatic dysfunction, hepatosplenic conditions,
      pleuritic chest pain, slipping rib syndrome.Treatment: The athlete underwent 4
      months of conservative treatment (eg, activity modification, ice, ultrasound, hot
      packs, nonsteroidal anti-inflammatory drugs) after the injury, independently
      sought chiropractic intervention (12 treatments) 4 to 6 months postinjury, was
      referred to physical therapy (10 visits) by a nonsurgical sports medicine
      physician 6 to 8 months postinjury, and finally underwent surgical intervention 9
      months after the onset of the initial symptoms.Uniqueness: Slipping rib syndrome
      was first described in 1919. However, many health care professionals who are
      involved with diagnosing and treating athletes and active individuals (eg,
      athletic trainers, physicians) are relatively unfamiliar with this
      musculoskeletal condition.Conclusions: It is important for clinicians and team
      physicians to familiarize themselves with and consider the diagnosis of slipping
      rib syndrome when assessing and managing individuals with persistent abdominal
      and/or thoracic pain.

PMID- 15970960
TI  - The Prediction of Intracranial Injury After Minor Head Trauma in the Pediatric
      Population.
AB  - Reference: Dunning J, Batchelor J, Stratford-Smith P, et al. A meta-analysis of
      variables that predict significant intracranial injury in minor head trauma. Arch
      Dis Child. 2004;89:653-659.Clinical Question: Which clinical signs or symptoms of
      minor head trauma are predictive of intracranial hemorrhage in children and
      adolescents?Data Sources: Investigations were identified by MEDLINE and EMBASE
      searches from 1990 through 2002 by a search of the grey literature and by
      contacting experts for additional papers. The search terms were selected to find
      all studies reporting intracranial hemorrhage (ICH) or complications after head
      trauma.Study Selection: A full systematic review was conducted, and all cohort or
      nested cohort studies that presented data on minor head injuries in children less
      than 18 years old, with or without ICH, were identified. Studies were then judged
      for inclusion based on the presentation of a series of at least 100 patients and
      a documented reliable standard for the detection of ICH for all patients in the
      study. The use of computed tomography (CT) and medical follow-up was considered
      an acceptable gold standard. Intracranial hemorrhage was defined as any
      abnormality detected on the CT scan due to the traumatic presence of
      extravascular blood. Minor head trauma was defined as patients presenting with a
      Glasgow Coma Scale (GCS) score of 13-15.Data Extraction: Seven clinical
      correlates were used for data extraction, including skull fracture, headache,
      vomiting, focal neurology, seizure, loss of consciousness, and a GCS score of
      less than 15. Data were analyzed using a pooled estimate of the relative risk
      ratio with a random-effects model.Main Results: The searches identified a total
      of 2134 studies for the initial review. After an abstract review by 2 independent
      examiners, 98 studies were identified for a full-paper review. Each study was
      graded on a 4-point scale according to the level of evidence provided, using
      scales consistent with the Oxford Centre for Evidence-Based Medicine and the
      National Institute for Clinical Excellence. Thirty-four of these articles were of
      adequate quality for inclusion; however, many did not include data that could be
      separated into a specific data set for children, had too small a sample size, or
      lacked enough data on individual correlates to head trauma. Nineteen studies
      provided data on children, but 3 of these were excluded due to poor quality or
      lack of a reported CT scan, leaving a total of 16 studies for the meta
      analysis.The analysis included a total of 22 420 patients ranging between 0 and
      18 years of age. The meta-analysis showed a significant increased relative risk
      of ICH for patients sustaining loss of consciousness (2.23), GCS <15 (5.51),
      skull fracture (6.13), and focal neurology (9.43). No significant increases in
      risk for headache (1.02), vomiting (0.878), or seizure (2.82) were noted;
      however, heterogeneity was significant for this last correlate. The prevalence of
      ICH ranged from 1.3 to 36%, supporting the notion of a large amount of
      heterogeneity or variability in the inclusion criteria among the
      studies.Conclusions: These findings demonstrate that loss of consciousness,
      decreased level of consciousness (GCS <15), skull fracture, and focal neurology
      are risk factors for ICH in the pediatric population. However, these findings are
      not definitive enough to establish pediatric head-injury guidelines regarding CT
      scanning or admission to hospital after minor head trauma.

PMID- 15970963
TI  - Direct optical emission spectroscopy of liquid analytes using an electrolyte as a
      cathode discharge source (ELCAD) integrated on a micro-fluidic chip.
AB  - Atomic emission detection of metallic species in aqueous solutions has been
      performed using a miniaturised plasma created within a planar, glass micro
      fluidic chip. Detection was achieved using an Electrolyte as a Cathode Discharge
      source (ELCAD) in which the sample solution itself is used as the cathode for the
      discharge. To realise the ELCAD technique within a micro-fluidic device, a
      parallel liquid-gas flow was set up in a micro-channel and a glow discharge
      ignited between the flowing liquid sample surface and a metal wire anode. The
      detection of copper and sodium was achieved, using atmospheric pressure air as a
      carrier gas, by observation of atomic emission lines of copper at 324 nm, 327 nm,
      511 nm, 515 nm and 522 nm and an atomic emission line of sodium at 589 nm using a
      commercially available miniaturised spectrometer. A total electrical power of
      less than 70 mW was required to sustain the discharge. A semi-quantitative,
      absolute detection limit of 17 nmol s(-1) was obtained for sodium with a sample
      flow rate of 100 microL min(-1) and an integration time of 100 ms in air at
      atmospheric pressure. The volume required for such detection is approximately 170
      nL. Further analysis was performed with an Echelle spectrometer using both argon
      and air as a carrier gas. The geometry and flow rates used demonstrate the
      feasibility of integrating such micro-plasmas into other micro-fluidic devices,
      such as miniaturised CE devices, as a method of detection. The potential for
      using such micro-plasmas within highly portable miniaturised systems and mu-TAS
      devices is presented and discussed.

PMID- 15970964
TI  - Microfluidic chip-based liquid-liquid extraction and preconcentration using a
      subnanoliter-droplet trapping technique.
AB  - A robust and simple approach for microfluidic liquid-liquid (L-L) extraction at
      the subnanoliter-scale was developed for on-chip sample pretreatment. Organic
      solvent droplets of a few hundred pL were trapped within micro recesses
      fabricated in the channel walls of a microfabricated glass chip. L-L extraction
      was performed by delivering aqueous samples through the channel, with the sample
      stream continuously flowing adjacent to the droplets. The analytes in aqueous
      streams were enriched within the droplet with high preconcentration factors owing
      to both phase transfer and dissolution of organic solvent into the bypassing
      aqueous sample. An aqueous solution of butyl rhodamine B (BRB) and 1-hexanol were
      used, respectively, as sample and extractant to demonstrate the performance of
      the system. The fluorescence intensity of the dye extracted into the droplet was
      monitored in situ by LIF. The system proved to be an efficient means for
      achieving high enrichment factors of over 1000, with sample consumption of a few
      microL. Quantitative measurement of the extracted analyte was achieved with a
      linear response in the range 1 x 10(-9)-8 x 10(-7) M BRB. The precision of the
      measured fluorescence values for a 10(-7) M BRB standard with a 12.5 min
      preconcentration period was 6.6% RSD (n = 5).

PMID- 15970965
TI  - PDMS microfludic device for optical detection of protein immunoassay using gold
      nanoparticles.
AB  - A simple but highly specific immunoassay system for goat anti-human IgG has been
      developed using gold nanoparticles and microfluidic techniques. The assay is
      based on the deposition of gold nanoparticles that are coated with protein
      antigens in the presence of their corresponding antibodies to microfluidic
      channel surface. The effects of time accumulation, the flow velocity, and the
      concentration of antibodies to the red light absorption percentage (RAP) of
      deposition were investigated with an ordinary optical microscope. By controlling
      the reaction time and flow velocity, a dynamic range of 3 orders of magnitude and
      a detection sensitivity of 10 ng ml(-1) of goat anti-human IgG were achieved.
      Because of its simplicity and flexibility, this new technique should be useful
      for fast, highthroughput screening of antibodies in clinical diagnostic
      applications.

PMID- 15970966
TI  - Long-term stable electroosmotic pump with ion exchange membranes.
AB  - We present the design, fabrication and test of a novel inline frit-based
      electroosmotic (EO) pump with ion exchange membranes. The pump is more stable
      than previous types due to a new flow component that ensures a controlled width
      of the diffusion layer close to the ion exchange membranes. The pump casing is
      constructed in polymers while the EO active part, the frit, is made in a
      nanoporous silica. The pressure capability of the pump is Deltapm/DeltaV = 0.15
      bar V(-1). The flow rate to current ratio is Qm/I = 6 microL min(-1) mA(-1). This
      translates to Deltapm = 4.5 bar and Qm = 6 microL min(-1) at DeltaV = 30 V. The
      pump has been tested with four different buffer concentrations. In order to
      investigate day-to-day reproducibility each Q-p pump characteristic has been
      recorded several times during hour-long operation runs under realistic operating
      conditions.

PMID- 15970967
TI  - A serpentine laminating micromixer combining splitting/recombination and
      advection.
AB  - Mixing enhancement has drawn great attention from designers of micromixers, since
      the flow in a microchannel is usually characterized by a low Reynolds number (Re)
      which makes the mixing quite a difficult task to accomplish. In this paper, a
      novel integrated efficient micromixer named serpentine laminating micromixer
      (SLM) has been designed, simulated, fabricated and fully characterized. In the
      SLM, a high level of efficient mixing can be achieved by combining two general
      chaotic mixing mechanisms: splitting/recombination and chaotic advection. The
      splitting and recombination (in other terms, lamination) mechanism is obtained by
      the successive arrangement of "F"-shape mixing units in two layers. The advection
      is induced by the overall three-dimensional serpentine path of the microchannel.
      The SLM was realized by SU-8 photolithography, nickel electroplating, injection
      molding and thermal bonding. Mixing performance of the SLM was fully
      characterized numerically and experimentally. The numerical mixing simulations
      show that the advection acts favorably to realize the ideal vertical lamination
      of fluid flow. The mixing experiments based on an average mixing color intensity
      change of phenolphthalein show a high level of mixing performance was obtained
      with the SLM. Numerical and experimental results confirm that efficient mixing is
      successfully achieved from the SLM over the wide range of Re. Due to the simple
      and mass producible geometry of the efficient micromixer, SLM proposed in this
      study, the SLM can be easily applied to integrated microfluidic systems, such as
      micro-total-analysis-systems or lab-on-a-chip systems.

PMID- 15970968
TI  - Chaotic micromixers using two-layer crossing channels to exhibit fast mixing at
      low Reynolds numbers.
AB  - We report two chaotic micromixers that exhibit fast mixing at low Reynolds
      numbers in this paper. Passive mixers usually use the channel geometry to stir
      the fluids, and many previously reported designs rely on inertial effects which
      are only available at moderate Re. In this paper, we propose two chaotic
      micromixers using two-layer crossing channels. Both numerical and experimental
      studies show that the mixers are very efficient for fluid manipulation at low
      Reynolds numbers, such as stretching and splitting, folding and recombination,
      through which chaotic advection can be generated and the mixing is significantly
      promoted. More importantly, the generation of chaotic advection does not rely on
      the fluid inertial forces, so the mixers work well at very low Re. The mixers are
      benchmarked against a three-dimensional serpentine mixer. Results show that the
      latter is inefficient at Re = 0.2, while the new design exhibits rapid mixing at
      Re = 0.2 and at Re of O(10(-2)). The new mixer design will benefit various
      microfluidic systems.

PMID- 15970969
TI  - Imaging of peptide adsorption to microfluidic channels in a plastic compact disc
      using a positron emitting radionuclide.
AB  - A method for studying peptide-surface interactions within microfluidic channels
      by radionuclide imaging is described. With the high surface area-to-volume ratio
      of channels in miniaturised devices, combined with low amounts of analyte, non
      specific peptide adsorption is a critical issue. The objective of the study was
      therefore to develop a method capable of direct detection of adsorbed peptide
      within microfluidic channels. A micro-device consisting of channels moulded in a
      plastic compact disc was chosen for the study, together with two selected
      peptides of different lengths and isoelectric point (pI) values. A bifunctional
      chelator, DOTA, was attached to the peptide by conjugation and labelled with the
      short-lived positron emitting radionuclide 68Ga. Quantitative images of
      radiotracer distribution within the microfluidic channels were obtained using a
      PhosphorImager system. The power of the method was demonstrated by the ability to
      clearly measure changes in adsorption when varying a number of parameters that
      typically affect peptide adsorption. These included surface modifications,
      analyte concentration, pH, and ionic strength. Additionally, two quantification
      methods were developed and compared. Radionuclide imaging also permitted
      visualisation of adsorption and release processes in microchannel chromatographic
      columns. The results suggest that radionuclide imaging is a suitable tool not
      only for the study of peptide adsorption to the microchannels presented in this
      study but also as a versatile tool to measure peptide-surface interactions in a
      wide variety of miniaturised structures and devices.

PMID- 15970970
TI  - Shear-driven pumping and Fourier transform detection for on chip circular
      chromatography applications.
AB  - A circular, shear-driven pumping system combined with Fourier Transform detection
      has been developed for the application of chip based cyclic chromatography. Using
      this system, it is possible to perform an injection of a sample plug into a
      circular micro-channel and then drive the sample through the channel, using shear
      flow induced by a rotation stage. High pumping rates at uniform speeds are
      attainable with this system with very little heat production. Typical pumping
      rates of up to 1.423 mm s(-1) +/- 2 microm s(-1) were used in experiments
      although much higher rates >14 mm s(-1) are also possible with this system.
      Fluorescence detection was used to detect a sample plug of Coumarin dyes, flowing
      around the channel. A coating of porous polymethacrylate was used to immobilise
      RP-HPLC beads onto the glass surface and was applied to the glass micro-channel
      by selective photopolymerisation. This coating acted as a stationary phase and
      differences in retention time were observed for an injection of Coumarin dyes for
      different methanol-water, mobile phase ratios. Full sample retention occurred for
      30 : 70 (v/v) methanol-water whereas no retention occurred for 92 : 8 (v/v)
      methanol-water which can be expected for such a reverse phase, open tubular
      system. Fourier transform detection applied to the fully retained and non
      retained cases showed frequency domain data from a single detection point
      corresponding to that which may be expected from shear flow theory.

PMID- 15970971
TI  - An integrated disposable dye clad leaky waveguide sensor for micro-TAS
      applications.
AB  - An integrated, disposable, dye clad leaky waveguide (DCLW) device has been
      fabricated and tested for both refractive index and fluorescence detection in mu
      TAS applications. The chip comprises the required flow geometry and optical
      coupling elements in a robust device that is relatively simple and inexpensive to
      fabricate. Disposable DCLW chips were fabricated at room temperature by spin
      coating both the dye and silica sol-gel waveguiding layers on a polymer substrate
      which contained injection moulded grating coupler. These devices have been
      designed to increase the interaction of the evanescent field light at the channel
      wall and with the sample in the channel. The DCLW device has been used to detect
      changes in the refractive index of different percentages of glycerol solutions
      and to detect low concentrations down to 10(-12) M fluorescein using a grating
      coupler.

PMID- 15970972
TI  - Continuous particle separation in a microchannel having asymmetrically arranged
      multiple branches.
AB  - A new method for continuous size separation and collection of particles in
      microfabricated devices, asymmetric pinched flow fractionation (AsPFF), has been
      proposed and demonstrated. This method improves the separation scheme of pinched
      flow fractionation (PFF), which utilizes a laminar flow profile inside a
      microchannel. In this study, multiple branch channels with different channel
      dimensions were arranged at the end of the pinched segment, so that the flow rate
      distributions to each branch channel were varied, and a large part of the liquid
      was forced to go through one branch channel (drain channel). In the proposed
      channel system, the flow profile inside the microchannel was asymmetrically
      amplified, enabling the separation of one-order smaller particles compared with
      PFF. After introducing the method, we examined the effect of the asymmetric
      amplification by controlling the outlet of the drain channel. Also, a mixture of
      1.0 approximately 5.0 microm particles was separated, and erythrocytes were
      successfully separated from blood. The results indicate that the AsPFF method
      could be applied to the separation of much smaller-size particles, since more
      precise separation can be achieved simply by changing the geometries of branch
      channels.

PMID- 15970973
TI  - Fluorescence correlation spectroscopy for flow rate imaging and monitoring-
      optimization, limitations and artifacts.
AB  - We recently demonstrated a new method for mapping fluid velocities in 3
      dimensions and with exceptionally high spatial resolution for the
      characterization of flow in microfluidic devices. In the method, a colloidal
      suspension containing fluorescent tracer particles, dye doped polymer spheres, is
      pumped through a microchannel and confocal microscopy combined with fluorescence
      correlation spectroscopy is used to measure fluid velocities. In this report, we
      further characterize the technique and report on optimizations that allow a 5
      fold increase in speed of single point velocity measurements. This increase in
      measurement speed will yield a 25 fold reduction in the time needed to collect a
      complete velocity image. The precision of measured velocities was characterized
      as a function of tracer particle concentration, measurement time, and fluid
      velocity. In addition, we confirm the linearity of the measurement method
      (velocity vs. applied pressure) over a range of velocities spanning four orders
      of magnitude. Furthermore, we demonstrate that an artifact in velocity
      measurements using fluorescence correlation spectroscopy (FCS) that was
      interpreted by others as being caused by optical trapping forces is actually an
      artifact caused by detector saturation and can be avoided by careful choice of
      experimental conditions.

PMID- 15970974
TI  - [Effects of gastric bypass on weight, blood glucose, serum lipid levels and
      arterial blood pressure in obese patients].
AB  - BACKGROUND: Type 2 diabetes, hypertension and serum lipid abnormalities are
      common among obese people and they should improve with weight reduction. AIM: To
      study the outcome of these abnormalities after bariatric surgery in morbid
      obesity patients. MATERIAL AND METHODS: Two hundred thirty two morbid obese
      patients subjected to gastric bypass, were evaluated in the preoperative period
      and every three months after surgery, during a minimum of 12 months. Clinical
      evolution, blood glucose, serum insulin, insulin resistance measured with the
      homeostasis model assessment (HOMA) and serum lipid levels were analyzed.
      RESULTS: In the preoperative period, 17% had type 2 diabetes, 49% had abnormal
      serum lipid levels and 25% had high blood pressure. Sixty six percent had at
      least one of these abnormalities and 20% had more than one. During follow up,
      body mass index decreased from 44 to 29.3 kg/m2. Total and HDL cholesterol, blood
      glucose and insulin resistance significantly decreased from the third month after
      surgery. Diabetes disappeared in 97% of diabetic subjects, blood pressure
      normalized in 53% of subjects with hypertension and serum lipid levels returned
      to normal in 88% of subjects with dyslipidemia. CONCLUSIONS: Gastric bypass in
      morbid obese patients achieves a significant and important weight reduction that
      results in significant reductions in the frequency of diabetes, dyslipidemia and
      hypertension among operated obese subjects.

PMID- 15970975
TI  - [Lung diseases among HIV infected patients admitted to the "Instituto Nacional
      del Torax" in Santiago, Chile].
AB  - BACKGROUND: Pulmonary diseases are common among HIV infected patients. The
      prevalence of the different diseases varies greatly. AIM: To identify the
      different pulmonary diseases that affect a Chilean population of HIV infected
      patients and to identify factors associated with in hospital mortality. MATERIAL
      AND METHODS: Retrospective review of the clinical records of all HIV infected
      patients with lung diseases discharged from our institution during a period of
      3.5 years. Collection of demographic and biomedical data. RESULTS: One hundred
      seventy one patients (aged 35.7 years, 86% men) had 236 episodes of lung
      diseases. Only 13.5% of the patients were receiving antiretroviral therapy and
      18% were on pneumocystis prophylaxis. Infectious diseases accounted for 87% of
      the discharges, neoplasm for 5.1%. Pneumocystis jirovecii infection was
      responsible for 37.7% of the episodes, community acquired pneumonia was seen in
      24.1% and mycobacterial diseases in 14.4%. Two or more conditions were present in
      13.6%. Death during hospital stay occurred in 19.5%. Multivariate analysis
      identified pneumothorax as the only significant independent predictor of in
      hospital mortality in patients with pneumocystis pneumonia, while nosocomial
      pneumonia was the only predictor of death among patients with non-pneumocystis
      pulmonary diseases. CONCLUSIONS: Infectious diseases were the main cause of
      hospitalization among Chilean HIV infected patients. Mortality among these
      patients remains high. Appropriate antiretroviral therapy and prophylaxis may
      alter pulmonary disease prevalence in the future. Every effort should be made to
      avoid the development of pneumothorax and nosocomial pneumonia.

PMID- 15970976
TI  - [Pediatric non-invasive ventilation for acute respiratory failure in an
      Intermediate Care Unit].
AB  - BACKGROUND: Pediatric noninvasive ventilation (NIV) is infrequently used for
      acute respiratory failure (ARF), BiPAP/CPAP applied through nasal mask can be
      attempted if strict selection rules are defined. AIM: To evaluate the outcome of
      NIV in a Pediatric Intermediate Care Unit. MATERIAL AND METHODS: The medical
      records of 14 patients (age range 1 month-13 years, six female), who participated
      in a prospective protocol of NIV from January to October 2004, were reviewed.
      Oxygen therapy, delivered through a reservoir bag attached to the ventilation
      circuit, was used to maintain SaO2 over 90%. RESULTS: The main indication of
      BiPAP, in 80% of cases, was pulmonary restrictive disease. Indications of NIV
      were acute exacerbations in patients with chronic domiciliary NIV in three
      patients, hypoxic ARF in six and hypercapnic ARF in five. The diagnoses were
      pneumonia/atelectasis in seven patients, bilateral extensive pneumonia in three,
      RSV bronchiolitis in two, apnea in one, and asthma exacerbation in one. Only one
      patient required intubation for mechanical ventilation, all others improved. The
      procedures did not have complications. NIV lasted less than three days in 5
      patients, 4 to 7 days in four patients and more than 7 days in five. One third of
      the patients required fiberoptic bronchoscopy for massive or lobar atelectasis
      and one third remained on domiciliary NIV program. CONCLUSIONS: NIV can be useful
      and safe in children with ARF admitted to a Pediatric Intermediate Care Unit. If
      strict inclusion protocols are followed, NIV might avoid mechanical ventilation.

PMID- 15970977
TI  - [Prevalence of latex hypersensitivity in operating room workers of the University
      of Chile Clinical Hospital].
AB  - BACKGROUND: Health care workers (HCW) are a high risk group for developing
      natural rubber latex (NRL) hypersensitivity and allergy. Some studies showed a
      correlation between time and frequency of exposure to NRL gloves and
      hypersensitivity, but a recent meta-analysis showed no clear evidences for such
      assumption. AIM: To determine the prevalence of NRL hypersensitivity and allergy
      in a group of HCW at the University of Chile Clinical Hospital. MATERIALS AND
      METHODS: Ninety five HCW (aged 37+/-10 years, 59 females) were interviewed about
      time of exposure, atopic diseases and latex-related allergy symptoms. Different
      NRL extracts and seven NRL gloves brands were tested by the prick test method.
      RESULTS: Twenty four workers (25%, 95% CI = 16.9%-35.2%) were sensitized. No
      gender differences were found. No symptomatic cases were found in the sensitized
      group. In the workplace, six and two non sensitized subjects had respiratory
      symptoms or contact urticaria, respectively. Sensitivity to bananas, avocadoes,
      kiwi and chestnut was not significantly more common among latex sensitive
      individuals. No differences between sensitized and non sensitized subjects were
      observed for the presence of atopic diseases or the mean number of years at the
      workplace. The sensitization rate to NRL increased along with years of work, from
      18.6% in patients working less than 10 years, to 28.1% in the group between 10
      and 20 years and to 35% in those working more than 21 years (p=0.693).
      Sensitization was also related to the weekly hours of exposure: 1-10 hours, 17%;
      11-20 hours, 23.5%; 21-30 hours, 50% and 31-40 hours, 28.5% (p=0.036).
      CONCLUSIONS: Sensitization increased proportionally to the years and weekly hours
      wearing NLR gloves. We did not find symptomatic patients in the sensitized group.

PMID- 15970978
TI  - [Usefulness of C-reactive protein for the diagnosis of bacterial infections in
      children. A review].
AB  - Although C-Reactive protein (CRP) was described more than 70 years ago and it
      still is commonly used in practice, studies exploring its usefulness persist
      while some propose its replacement by other inflammatory acute-phase-mediators.
      The aim of this clinical review is to answer the question if CRP measurement
      warrant clinical decisions for febrile children because it discriminates between
      bacterial from non bacterial etiologies. We made a systematic search by means of
      MEDLINE, SciELO and LILACS with the following MESH terms: "C-reactive protein",
      "bacterial", "infection", "children", "diagnosis" or "detection", besides the
      Haynes selector for articles on diagnosis, between 1950 and 2004. Selection data
      extraction and critical appraisal were independently made by the two authors,
      following standard criteria. We selected 7 primary articles, 3 clinical reviews
      and two randomized clinical trials. There was no disagreement between reviewers.
      Only one of the clinical reviews followed standard guidelines; two reviews
      concluded that no isolated CRP values would warrant to make decisions on starting
      or withholding antimicrobial therapy in febrile children. All primary articles
      showed methodological flaws in basic validity criteria. Both randomized clinical
      trials showed that CRP results did not change either doctor's decisions about
      antimicrobial prescriptions nor the studied patients' prognosis. We did not find
      evidences that could warrant the use of CRP for the defined problem in
      Pediatrics. Main problems affecting validity of studies on CRP as diagnostic
      resource are the lack of laboratory methods uniformity--including the gold
      standard make up--the heterogeneity of cut off points, clinical spectrum
      inappropriateness of study groups as well as the resulting diversity of the fixed
      indexes values. Moreover, no validation of this test in children population has
      been made so far.

PMID- 15970979
TI  - [Congenital malformations among offspring of diabetic women].
AB  - BACKGROUND: The risk of congenital malformations is two to three times higher
      among women with diabetes mellitus before pregnancy. Gestational diabetes is
      emerging as a risk factor for malformations. AIM: To study the rate and type of
      congenital malformations among offspring of women with pre-gestational or
      gestational diabetes. MATERIAL AND METHODS: A search in the databases of the
      Collaborative Latin American Study for Congenital Malformations and of the
      Neonatology Unity of The University of Chile Clinical Hospital. All births from
      January 1998 through June 2004 were investigated. RESULTS: In the study period,
      13,965 births occurred, of which 0.7% were stillbirths and 8.1% had
      malformations. A total of 295 women (2.1%) had diabetes (gestational diabetes in
      1.8% and pre gestational diabetes in 0.3%). The prevalence of congenital
      malformations was 14% and 18.3% among offspring of mothers with pre-gestational
      and gestational diabetes, respectively (p=NS). The prevalence of congenital
      malformations among offspring of non diabetic women was 7.9% (p <0.001 with
      respect to diabetic women). Major malformations were found in 83% and 70% of
      malformed offspring of women with pre-gestational and gestational diabetes,
      respectively. CONCLUSIONS: Pregnant women with pre-existing or gestational
      diabetes have a higher risk of giving birth a child with malformations.

PMID- 15970980
TI  - [Morbidity and mortality for oral and pharyngeal cancer in Chile].
AB  - BACKGROUND: Most oral cancers are squamous cell carcinomas (90%) which are two to
      four times more common in men than in women. The reasons for these differences
      are associated with exposure to factors such as tobacco and alcohol. Age is also
      considered as a risk factor (about 90% of the cases are diagnosed after 45 years
      of age). AIM: To analyze the frequency of oral cavity cancer during the last
      years in Chile. MATERIAL AND METHODS: Mortality rates were obtained from death
      records of the "Instituto Nacional de Estadisticas" and publications of the World
      Health Organization, from 1955 to 2002. Morbidity from 1969 to 2002 was obtained
      from hospital discharge records of the Chilean Ministry of Health. RESULTS: Oral
      cancer corresponded to 1.6% of total cancer cases in Chile, with a male:female
      ratio of 2.3 to 1. Deaths due to oral cancer was 1% of all cancer deaths, with a
      male:female ratio of 2.8 to 1. The morbidity rate for both genders increased
      while the mortality rate was relatively constant. However, we observed an
      increase in the mortality rate among women from 1980 to 2002, associated with
      more than 100% increase in the frequency of smoking, between 1970 and 1998. The
      most common anatomical location was the tongue. CONCLUSIONS: The incidences of
      oral cancer is increasing in Chilean women, but men are more commonly affected.

PMID- 15970981
TI  - [CT angiography as the diagnostic and decision making method used for surgical
      indication in pulmonary hypertension due to chronic thromboembolism. Report of
      one case].
AB  - Pulmonary hypertension due to chronic pulmonary thromboembolism is frequently
      underdiagnosed and has a very poor prognosis if untreated. When the presence of
      central pulmonary artery thrombus is confirmed, thromboendarterectomy is the
      treatment of choice, with very good results. We report a 28 years old male with
      two previous episodes of deep venous thrombosis (DVT) who was admitted due to 8
      months of progressive shortness of breath and a syncope. He underwent a CT
      pulmonary angiogram and an echocardiogram. Severe pulmonary hypertension was
      confirmed, secondary to a chronic pulmonary thromboembolism with an overlapped
      acute component. He received systemic thrombolysis with partial thrombus
      disappearance. Therefore a pulmonary thromboendarterectomy was performed and an
      inferior vena cava filter was placed. The patient was discharged with marked
      improvement in his functional capacity.

PMID- 15970982
TI  - [Chest pain and ST segment abnormalities in patients with accessory
      atrioventricular pathways. Report of three cases].
AB  - We report three patients with pre-excitation syndrome that resembled an acute
      coronary syndrome. A 65 years old woman, consulting in the emergency room for
      palpitations and retrosternal pain. EKG showed regular tachycardia and ST
      depression that reverted spontaneously after an episode of vomiting. A subsequent
      EKG demonstrated a pre-excitation syndrome and the accessory pathway was
      fulgurated. A 18 years old male presenting with tachycardia and chest pain
      elicited during exercise. An EKG showed a pre-excitation syndrome and ST segment
      elevation in V2 and V3. A coronary angiogram was normal. The accessory pathway
      successfully fulgurated. A 63 years old woman that presented tachycardia while
      exercising. She was subjected to an electrical cardioversion. An
      electrophysiological study showed an accessory pathway that was successfully
      fulgurated.

PMID- 15970983
TI  - [Potentially productive years of life lost among adults in Metropolitan Santiago.
      Is there an improvement in equality?].
AB  - BACKGROUND: Potentially productive years of life lost (PPYLL) is an impact
      measure that illustrates the lost that a society suffers as a consequence of
      deaths of young people or premature deaths. AIM: To study the evolution of PPYLL
      in adults in the periods 1994-1996 and 1999-2001, according to sex, income
      quintiles and main diagnostic groups in the communities of Metropolitan Santiago.
      MATERIAL AND METHODS: Ecological study analyzing the population of Metropolitan
      Santiago, that represents 36% of the national population. A total of 87,969
      deaths in people aged 20 to 79 years were analyzed. RESULTS: There is a greater
      amount of PPYLL among the poorest quintiles and men represent the higher number
      of PPYLL. In the different analyzed periods, all quintiles experienced a
      reduction in PPYLL. According to diagnosis, endocrine diseases experienced the
      greater decrease between periods, followed by respiratory disease. Noteworthy was
      the increase of PPYLL due to infectious diseases. PPYLL due to digestive diseases
      was 2.3 higher in the poorest quintile, as compared with the wealthiest quintile
      (20/20 ratio). The ratio for traumatic disease was 1.8. CONCLUSIONS: When
      comparing both periods, there is a net gain of potentially productive years of
      life in all income quintiles and in both genders.

PMID- 15970984
TI  - [Use of positron-emission tomography with F18-fluorodeoxyglucose for the
      assessment of lung lesions suspicious of malignancy].
AB  - Positron-emission tomography (PET) with F18-fluorodeoxyglucose (FDG) is very
      helpful in the evaluation and management of lung lesions. It is specially useful
      for the characterization of solitary nodules, for the staging, evaluation of
      recurrence and therapeutic response in non-small cell lung cancer, for the
      evaluation of small cell lung cancer and for the assessment of pulmonary
      metastases. This article is a literature review on PET with FDG in lung cancer. A
      preliminary analysis of PET results at the Military Hospital in Santiago, Chile,
      is also presented.

PMID- 15970985
TI  - [Interpreting the results of an article about therapy].

PMID- 15970986
TI  - [Critical appraisal: Should atenolol be the first choice for primary
      hypertension? Carlberg B, Samuelsson O, Lindholm L. Atenolol in hypertension: is
      it a wise choice? Lancet 2004; 364: 1684-89].

PMID- 15970987
TI  - [The debate about the right to die].
AB  - The Right to Die is a debatable issue and some basic notions need to be clarified
      to discuss it. Death needs to be recognized as part of human life. The goal of
      medicine is to avoid pain and alleviate suffering, to prevent premature death and
      when this is not possible, to let it occur peacefully. The concept of euthanasia
      is unclear, which increases the confusion on end-of-life topics. The term
      euthanasia should be used only when referring to medical acts performed to
      produce the patient's death, with the intention of terminating his/her suffering.
      It is what is usually called "active" euthanasia, which can be voluntary or
      involuntary. It is essential to understand the difference between producing and
      allowing death. This will permit timely decisions about limiting or withdrawing
      treatments, that can be disproportionate or that are only prolonging suffering.
      Limiting treatments does not mean to abandon the patient but rather to redefine
      his needs, such as pain treatment, prevention of complications, and relief of
      suffering. The ethic rationale for these decisions is the respect to the dignity
      of human life, and the estimation of proportionality or futility of each
      treatment. The physician's duty with the patient at the end of his life is to
      assist him in dying according to his values and to minimize his distress.

PMID- 15970988
TI  - [Recommendations to avoid conflicts of interest].

PMID- 15970989
TI  - [Pica, a strange symptom unveiled even in "Don Quixote"].
AB  - Pica, the compulsive eating of non edible substances, is known by the medical
      profession for centuries. In the novel by Miguel de Cervantes "Adventures of the
      famous knight Don Quixote de la Mancha'', there is a history in which "women that
      by caprice eat soil, plaster coal and other disgusting substances'' are
      mentioned. This description configures the clinical diagnosis of pica. This fact
      has not attracted the attention of the critics of Cervantes' novel, up to now.
      This unequivocal reference of pica suggests that iron deficiency anemia, caused
      by chronic hemorrhages in adults, was frequent in 1605, when the book was first
      published.

PMID- 15970990
TI  - [Emergency contraception, Levonorgestrel and ectopic pregnancy].

PMID- 15970992
TI  - Cultivated anaerobic acidophilic/acidotolerant thermophiles from terrestrial and
      deep-sea hydrothermal habitats.
AB  - Metabolic and phylogenetic diversity of cultivated anaerobic microorganisms from
      acidic continental hot springs and deep-sea hydrothermal vents was studied by
      molecular and microbiological methods. Anaerobic organotrophic enrichment
      cultures growing at pH 3.5-4.0 and 60 or 85 degrees C with organic energy sources
      were obtained from samples of acidic hot springs of Kamchatka Peninsula
      (Pauzhetka, Moutnovski Volcano, Uzon Caldera) and Kunashir Island (South Kurils)
      as well as from the samples of chimneys of East Pacific Rise (13 degrees N). The
      analyses of clone libraries obtained from terrestrial enrichment cultures growing
      at 60 degrees C revealed the presence of archaea of genus Thermoplasma and
      bacteria of genus Thermoanaerobacter. Bacterial isolates from these enrichments
      were shown to belong to genera Thermoanaerobacter and Thermoanaerobacterium,
      being acidotolerant with the pH optimum for growth at 5.5-6.0 and the pH minimum
      at 3.0. At 85 degrees C, domination of thermoacidophilic archaea of genus
      Acidilobus in terrestrial enrichments was found by both molecular and
      microbiological methods. Five isolates belonging to this genus possessed some
      phenotypic features that were new for this genus, such as flagellation or the
      ability to grow on monosaccharides or disaccharides. Analyses of clone libraries
      from the deep-sea thermoacidophilic enrichment cultures showed that the
      representatives of the genus Thermococcus were present at both 60 and 85 degrees
      C. From the 60 degrees C deep-sea enrichment, a strain belonging to
      Thermoanaerobacter siderophilus was isolated. It grew optimally at pH 6.0 with
      the minimum pH for growth at 3.0 and with salinity optimum at 0-2.5% NaCl and the
      maximum at 7%, thus differing significantly from the type strain. These data show
      that fermentative degradation of organic matter may occur at low pH and wide
      temperature range in both terrestrial and deep-sea habitats and can be performed
      by acidophilic or acidotolerant thermophilic prokaryotes.

PMID- 15970993
TI  - Gene replacement in Haloarcula marismortui: construction of a strain with two of
      its three chromosomal rRNA operons deleted.
AB  - Site-directed mutagenesis were done in Haloarcula marismortui using the strategy
      that Khorana and coworkers devised for deleting the bacteriorhodopsin gene from
      Halobacterium halobium [Krebs et al. Proc Natl Acad Sci USA 90:1987-1991 (1993)].
      Strains have been prepared from H. marsimortui, which normally has three rRNA
      operons, that are missing either its rrnB operon or both its rrnB and rrnC
      operons. In rich media, both strains grow at about the same rate as wild type.
      The G2099 in the 23S rRNA gene of the single operon strain was changed to A, and
      a three amino acid deletion was introduced into the gene for ribosomal protein
      L22 of the wild-type organism. The structural consequences of these and other
      such mutations can be determined with unusual accuracy because crystals of the
      large ribosomal subunit of H. marismortui diffract to atomic resolution.

PMID- 15970994
TI  - Community phylogenetic analysis of moderately thermophilic cyanobacterial mats
      from China, the Philippines and Thailand.
AB  - Most community molecular studies of thermophilic cyanobacterial mats to date have
      focused on Synechococcus occurring at temperatures of approximately 50-65 degrees
      C. These reveal that molecular diversity exceeds that indicated by morphology,
      and that phylogeographic lineages exist. The moderately thermophilic and
      generally filamentous cyanobacterial mat communities occurring at lower
      temperatures have not previously been investigated at the community molecular
      level. Here we report community diversity in mats of 42-53 degrees C recovered
      from previously unstudied geothermal locations. Separation of 16S rRNA gene
      defined genotypes from community DNA was achieved by DGGE. Genotypic diversity
      was greater than morphotype diversity in all mats sampled, although genotypes
      generally corresponded to observed morphotypes. Thirty-six sequences were
      recovered from DGGE bands. Phylogenetic analyses revealed these to form novel
      thermophilic lineages distinct from their mesophilic counterparts, within
      Calothrix, Cyanothece, Fischerella, Phormidium, Pleurocapsa, Oscillatoria and
      Synechococcus. Where filamentous cyanobacterial sequences belonging to the same
      genus were recovered from the same site, these were generally closely affiliated.
      Location-specific sequences were observed for some genotypes recovered from
      geochemically similar yet spatially separated sites, thus providing evidence for
      phylogeographic lineages that evolve in isolation. Other genotypes were more
      closely affiliated to geographically remote counterparts from similar habitats
      suggesting that adaptation to certain niches is also important.

PMID- 15970996
TI  - Nitrogenase activity and nifH expression in a marine intertidal microbial mat.
AB  - N(2) fixation, diazotrophic community composition, and organisms actively
      expressing genes for N(2) fixation were examined over at 3-year period (1997
      1999) for intertidal microbial mats on a sand flat located in the Rachel Carson
      National Estuarine Research Reserve (RCNERR) (Beaufort, NC, USA). Specifically,
      diel variations of N(2) fixation in the mats from the RCNERR were examined. Three
      distinct diel patterns of nitrogenase activity (NA) were observed. NA responses
      to short-term inhibitions of photosynthesis corresponded to one of the three
      patterns. High rates of NA were observed during peak O(2) production periods for
      diel experiments during summer months. Different types of NA diel variations
      correspond to different stages of mat development. Chloramphenicol treatments
      indicated that the mechanism of protein synthesis supporting NA changed
      throughout the day. Analysis of mat DNA and RNA gave further evidence suggesting
      that in addition to cyanobacteria, other functional groups were responsible for
      the NA observed in the RCNERR mats. The role of microbial diversity in the N(2)
      fixation dynamics of these mats is discussed.

PMID- 15970995
TI  - Aluminum-tolerant Pseudomonas fluorescens: ROS toxicity and enhanced NADPH
      production.
AB  - Aluminum (Al) triggered a marked increase in reactive oxygen species (ROS) such
      as O(2) (-) and H(2)O(2) in Pseudomonas fluorescens. Although the Al-stressed
      cells were characterized with higher amounts of oxidized lipids and proteins than
      controls, NADPH production was markedly increased in these cells. Blue native
      polyacrylamide gel electrophoresis (BN-PAGE) analyses coupled with activity and
      Coomassie staining revealed that NADP(+) -dependent isocitrate dehydrogenase
      (ICDH, E.C. 1.1.1.42) and glucose-6-phosphate dehydrogenase (G6PDH, E.C.
      1.1.1.49) played a pivotal role in diminishing the oxidative environment promoted
      by Al. These enzymes were overexpressed in the Al-tolerant microbes and were
      modulated by the presence of either Al or hydrogen peroxide (H(2)O(2)) or
      menadione. The activity of superoxide dismutase (SOD, E.C. 1.15.1.1), an enzyme
      known to combat ROS stress was also increased in the cells cultured in millimolar
      amounts of Al. Hence, Al-tolerant P. fluorescens invokes an anti-oxidative
      defense strategy in order to survive.

PMID- 15970997
TI  - Endocrine effects in Gammarus fossarum (Amphipoda): influence of wastewater
      effluents, temporal variability, and spatial aspects on natural populations.
AB  - In a field study, individuals of autochthounous populations of the amphipod
      Gammarus fossarum were examined for their maturity status, oocyte development,
      and biochemical parameters associated with their reproductive cycle. Variability
      in these parameters was related to abiotic exposure parameters varying in
      accordance to wastewater discharges, stream identity, and time. Patterns of all
      investigated parameters showed predominantly seasonal rather than spatial
      influence for both exposure and biologic effects. Single selected-effect
      parameters, however--such as the maturity index, late vitellogenic oocyte size
      and atresia, and the hsp90 level--responded to a sewage treatment plant discharge
      showing an estrogenic potential and also correlated significantly with the
      concentration of potential xenoestrogens at the different locations.

PMID- 15970998
TI  - The Jerusalem psychiatric mother-baby unit.
AB  - The Jerusalem mother and baby unit (MBU) is influenced by the psychoanalytical
      orientation of the staff, and the historical and cultural conditions surrounding
      the unit. Forty-three patients with 44 babies (one set of twins) were admitted in
      13 years, a rate of admission far from the theoretical demand. Schizophrenia,
      schizoaffective disorder and mood disorders have been the major diagnoses in more
      than 50% of the patients. Mothers with schizophrenia were significantly more
      likely to be admitted sooner after the birth than mothers without schizophrenia
      (p = 0.025). One infant was separated from the mother on discharge and four
      recommendations for adoption were given.

PMID- 15970999
TI  - A longitudinal study of psychiatric symptoms in primiparous women: relation to
      personality disorders and sociodemographic factors.
AB  - OBJECTIVE: To examine the prevalence of personality disorders (PDs) and elucidate
      the importance of PDs, sociodemographics and health-related factors for the
      development of psychiatric symptoms in primiparous women. METHOD: 625 primiparous
      women were assessed during pregnancy, three and 18 months following delivery. The
      Symptom Checklist-90 (SCL-90), the modified SCID-screen questionnaire and the
      Global Assessment of Functioning Scale (GAF) were used. RESULTS: The prevalence
      of PDs was 6.4%. PD was strongly associated with psychiatric symptoms during and
      after pregnancy. The most important factor predicting long-lasting mental
      problems was having a PD. A higher level of psychiatric symptoms was found in
      pregnancy than postpartum. Psychiatric caseness during pregnancy was strongly
      associated with caseness postpartum. In addition, socio-economic status, younger
      age and previous treatment for mental problems were identified as risk factors.
      CONCLUSION: The study indicates a strong association between long-lasting
      psychiatric illness and personality disorders in childbearing women. A strong
      association was also found between psychiatric symptoms during pregnancy and the
      postpartum period.

PMID- 15971000
TI  - Activated scramblase and inhibited aminophospholipid translocase cause
      phosphatidylserine exposure in a distinct platelet fraction.
AB  - Platelet procoagulant activity is mainly determined by the extent of surface
      exposed phosphatidylserine (PS), controlled by the activity of aminophospholipid
      translocase and phospholipid scramblase. Here, we studied both transport
      activities in single platelets upon stimulation with various agonists. Besides
      the formation of procoagulant microparticles, the results show that a distinct
      fraction of the platelets exposes PS when stimulated. The extent of PS exposure
      in these platelet fractions was similar to that in platelets challenged with Ca2+
      ionophore, where all cells exhibit maximal attainable PS exposure. The size of
      the PS-exposing fraction depends on the agonist and is proportional to the
      platelet procoagulant activity. Scramblase activity was observed only in the PS
      exposing platelet fraction, whereas translocase activity was exclusively
      detectable in the fraction that did not expose PS. We conclude that, irrespective
      of the agonist, procoagulant platelets exhibit maximal surface exposure of PS by
      switching on scramblase and inhibiting translocase activity.

PMID- 15971001
TI  - Transcriptional response to ionizing radiation in lymphocyte subsets.
AB  - Human lymphocyte subpopulations differ in their cellular responses to ionizing
      radiation. To shed light on the molecular basis of this effect, we characterized
      the transcriptional response to 1 Gy X-rays of CD4+ T lymphocytes. Of 18,433
      genes tested, 102 were modulated more than 1.5-fold. The majority of the strongly
      activated genes were p53 targets involved in DNA repair and apoptosis. The
      expression of three of these genes was further tested by quantitative RT-PCR in
      lymphocyte subpopulations [CD4+ and CD8+ T, CD19+ B, CD56+ natural killer cells
      and peripheral blood lymphocytes (PBLs)] from ten adult donors. In contrast to
      DDB2, TNFRSF10B and BAX were differentially modulated among the subpopulations
      and the PBLs, being more activated in irradiated CD19+ B and CD8+ T lymphocytes.
      The level of BAX activation in the various subpopulations correlated with the
      sensitivity of the cells to radiation, suggesting its possible role in the
      differential radiosensitivity of hematopoietic cell subsets.

PMID- 15971002
TI  - Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone
      treatment.
AB  - Recent reports describe successful treatment using copper chelation therapy in
      neurodegenerative animal models. However, the success claimed for chelation
      therapy in neurodegenerative diseases is still rather controversial. To acquire
      new information on copper metabolism/homeostasis, we utilized cuprizone, a very
      sensitive and selective copper-chelating agent with well-known neurotoxic
      properties, as a relevant chemical model in mice. Upon cuprizone treatment, mice
      developed a pronounced astrocytosis, with brain oedema and spongiosis
      characterised by vacuolisations of the neuropil predominantly in the white
      matter. In addition, cuprizone treatment severely altered copper and zinc
      homeostasis in the central nervous system (CNS) as well as in all other tissues
      examined, with increasing metal ion concentrations particularly in the CNS.
      Concomitant with this increase in the Cu and Zn concentration in the brain,
      metallothionein-I and -II were also highly immunoreactive in astrocyte,
      consistent with the astrocytosis and demyelination observed in our and other
      laboratories.

PMID- 15971003
TI  - Concerns regarding pelvic reconstructive surgery.

PMID- 15971004
TI  - The impact of pelvic organ prolapse on sexual function in women with urinary
      incontinence.
AB  - The aim of the study is to evaluate the impact of pelvic organ prolapse (POP) on
      sexual function in women with urinary incontinence (UI). In this retrospective,
      case-cohort study, we reviewed the medical records of all women evaluated for UI
      between March and November 2003. All patients completed the short forms of the
      Urogenital Distress Inventory, Incontinence Impact Questionnaire, and Pelvic
      Organ Prolapse/Urinary Incontinence Sexual Questionnaire. Women with stage two or
      greater POP, as determined by the pelvic organ prolapse quantification (POPQ)
      system, were compared to women with stage 0 or 1 POP. Sixty-nine women with POP
      and 47 women without POP were included. Patient demographics did not differ
      between the two groups. Women with POP were significantly more likely to report
      absence of libido (53% versus 30%, P=0.02), lack of sexual excitement during
      intercourse (46% versus 27%, P=0.05), and that they rarely experienced orgasm
      during intercourse (49% versus 30%, P=0.05). In conclusion, women with POP in
      addition to UI are more likely to report decreased libido, decreased sexual
      excitement, and difficulty achieving orgasm during intercourse when compared to
      women with UI alone.

PMID- 15971005
TI  - Chain orientation in natural rubber, Part I: the inverse yielding effect.
AB  - Inhomogeneous deformations are observed in stretched natural rubber of different
      crosslink density; the conditions of observation, nucleation and propagation are
      given in the first part of the paper. In samples of low crosslink density these
      inhomogeneities recall necking observed in others materials and in glassy
      polymers when the materials are drawn above a critical draw ratio. The difference
      is that in natural rubbers, NR, they nucleate and propagate at constant stress
      during unloading. This phenomenon, called inverse yielding appears during
      recovery only if the samples have been drawn previously in the hardening domain.
      During necking propagation the stress is constant. The mechanical and
      crystallinity properties of samples with and without inverse yielding are studied
      as a function of draw ratio, crosslink density and temperature. In the second
      part of the paper this transition zone (neck) of thickness 2 mm is studied by
      WAXS at the synchrotron source. From the orientation of NR crystallites and from
      the orientation of the stearic acid (2%, present in this type of rubber) we
      conclude that the deformation in the neck follows the flow lines. From the local
      crystallinity of the NR crystallites one deduces the local draw ratio across this
      transition zone. We suggest that in all these rubbers, which present a plateau of
      the recovery stress strain curve, micronecking exists. This effect is discussed
      in the framework of the Flory theory.

PMID- 15971006
TI  - Involvement of Ca2+ signaling in tachykinin-mediated contractile responses in
      swine trachea.
AB  - Neuropeptide tachykinins, present within sensory nerves, have been implicated as
      neurotransmitters involved in nonadrenergic and noncholinergic airway muscle
      contraction. The signal transduction pathways of tachykinins on muscle
      contraction and Ca2+ mobilization were investigated in swine trachea.
      Tachykinins, substance P (SP) and neurokinin A (NKA), concentration (1 nM to 1
      microM)-dependently induced contractile responses with removal of epithelium,
      whereas neurokinin B (NKB) did not alter the muscle tension. The SP- and NKA
      evoked muscle contractions were inhibited by NK1-R antagonist L732138, but not by
      either NK2-R antagonist MDL29913 or NK3-R antagonist SB218795. Consistently, SP
      elicited increase in [Ca2+]i was abolished by NK1-R antagonist, neither by NK2-R
      nor NK3-R antagonists. The SP-induced muscular responses were significantly
      inhibited by L-type Ca2+ channel blocker verapamil and withdrawal of external
      Ca2+. Caffeine (10 mM) or ryanodine (50 microM) also partly suppressed the SP
      induced muscle responses. Inhibition of inositol 1,4,5-trisphosphate (InsP3)
      receptor with 2-APB (75 microM) potently attenuated SP-evoked Ca2+ mobilization
      and muscle contraction, which was further inhibited by 2-APB under Ca2+-free
      external solution, but not completely. Unexpectedly, simultaneous blockade of
      InsP3 receptor and ryanodine receptor (RyR) by 2-APB and ryanodine enhanced SP
      evoked muscle contraction and Ca2+ mobilization. This potentiation was virtually
      abolished by removal of external Ca2+, suggesting native Ca2+ channels may
      contribute to this phenomenon. These results demonstrate that tachykinins produce
      a potent muscle contraction associated with Ca2+ mobilization via tachykinin NK1-
      R-dependent activation of multiple signal transduction pathways involving Ca2+
      influx and release of Ca2+ from InsP3- and ryanodine-sensitive Ca2+ stores.
      Blockade of both InsP3 receptor and RyR enhances the Ca2+ influx through native
      Ca2+ channels in plasma membrane, which is crucial to Ca2+ signaling in response
      to NK1 receptor activation.

PMID- 15971007
TI  - Biological pacemaker created by fetal cardiomyocyte transplantation.
AB  - BACKGROUND: The aim of this study was to investigate the feasibility of an
      alternative approach to electronic pacemaker by using spontaneously excitable
      cell grafts as a biological pacemaker in a large animal model of complete
      atrioventricular block. METHODS AND RESULTS: Dissociated male human atrial
      cardiomyocytes including sinus nodal cells were grafted into the free wall of the
      left ventricle in five female pigs. Three weeks after the injection of cell
      grafted solution/control medium the pigs underwent catheter ablation of the
      atrioventricular node (AV-node). After complete AV block was created, the
      idioventricular beat rate was more rapid in cell-grafted pigs than that in
      control pigs (86+/-21 vs. 30+/-10 bpm; P<0.001). Administering of isoprenalin
      significantly increased idioventricular rate from 86+/-21 to 117+/-18 bpm in the
      cell-grafted animals (P<0.01). Electrophysiological mapping studies demonstrated
      that the idioventricular rhythm originated from the cell-injection site.
      Polymerase chain reaction verifying the existence of SRY DNA in the cell
      injection site indicated that the grafted male cells were survived. Furthermore,
      the connexin-43 and N-cadherin positive junctions between donor cardiomyocytes
      and host cells were identified. CONCLUSION: Xenografted fetal human atrial
      cardiomyocytes are able to survive and integrate into the host myocardium, and
      show a pacing function that can be modulated by autonomic agents.

PMID- 15971008
TI  - Shear stress regulates gene expression in vascular endothelial cells in response
      to tumor necrosis factor-alpha: a study of the transcription profile with
      complementary DNA microarray.
AB  - We investigate the role of shear stress in regulating the gene expression in
      endothelial cells (ECs) in response to tumor necrosis factor-alpha (TNF-alpha).
      ECs were kept in static condition or pre-exposed to a high level (HSS, 20
      dynes/cm2) or a low level of shear stress (LSS, 0.5 dynes/cm2) for 24 h, and TNF
      alpha was added under static condition for 4 h. In static ECs, DNA microarray
      showed that TNF-alpha caused a significant increase in expression of 102 genes
      and a significant decrease in expression of 12 genes. Pre-shearing of ECs
      decreased the TNF-alpha-responsiveness of many pro-inflammatory, pro-coagulant,
      proliferative, and pro-apoptotic genes, whereas it increased the responsiveness
      of some antioxidant, anti-coagulant, and anti-apoptotic genes. LSS showed less
      regulatory effects than HSS on EC gene expression in response to TNF-alpha. The
      microarray data were confirmed by reverse-transcription polymerase chain reaction
      for 64 selected genes. Pre-shearing of ECs at HSS significantly inhibited the TNF
      alpha-induced p65 and p50 mRNA expressions and nuclear factor-kappaB (NF-kappaB)
      DNA binding activity. Inhibition of NF-kappaB activity with the p65-antisense or
      lactacystin under static condition blocked the expression of most of the genes
      that are TNF-alpha-inducible and shear stress-down-regulated. Our findings
      suggest that laminar shear stress serves protective functions against
      atherogenesis.

PMID- 15971009
TI  - A cross-cultural investigation of the role of foot size in physical
      attractiveness.
AB  - Disparate cultural practices suggest that small foot size may contribute to
      female attractiveness. Two hypotheses potentially explain such a pattern. Sexual
      dimorphism in foot size may lead observers to view small feet as feminine and
      large feet as masculine. Alternately, because small female feet index both youth
      and nulliparity, evolution may have favored a male preference for this attribute
      in order to maximize returns on male reproductive investment. Whereas the
      observational hypothesis predicts symmetrical polarizing preferences, with small
      feet being preferred in women and large feet being preferred in men, the
      evolutionary hypothesis predicts asymmetrical preferences, with the average
      phenotype being preferred in men. Using line drawings that varied only in regard
      to relative foot size, we examined judgments of attractiveness in nine cultures.
      Small foot size was generally preferred for females, while average foot size was
      preferred for males. These results provide preliminary support for the hypothesis
      that humans possess an evolved preference for small feet in females.

PMID- 15971010
TI  - Hostility and recidivism in sexual offenders.
AB  - In this study, we examined the association of hostility, as measured by the Buss
      Durkee Hostility Inventory (BDHI), with offence characteristics and recidivism in
      656 adult male sexual offenders. Hostility was significantly associated with
      having prior violent charges, the use of violence in the index sexual offence,
      sexual recidivism, and violent recidivism. After controlling for risk level, as
      measured by a modified version of the Rapid Risk Assessment for Sexual Offence
      Recidivism (RRASOR-mod), the significant association between hostility and sexual
      and violent recidivism remained. When examined by type of offender, hostility was
      significantly associated with recidivism in intrafamilial and extrafamilial child
      molesters, but not in rapists or mixed offenders. Given the predictive value of
      hostility independent of the RRASOR-mod, the present findings confirm and
      encourage treatment efforts directed toward the management of hostility and anger
      in sexual offenders.

PMID- 15971011
TI  - Erectile and ejaculatory problems in gay and heterosexual men.
AB  - The prevalence of erectile difficulties (ED) and problems with rapid ejaculation
      (RE) were studied in a convenience sample of gay men (n = 1379) and an age
      matched sample of heterosexual men (n = 1558). ED was reported more frequently by
      gay men and RE more frequently by heterosexual men. The heterosexual men were
      more likely to be in exclusive relationships and those in a current relationship
      (exclusive or non-exclusive) were more likely to report ED than those not in a
      relationship. Heterosexual men in an exclusive relationship were more likely to
      report RE than the rest. These associations were not found in the gay sample. The
      following personality traits were assessed as possible predictors of ED and RE:
      sexual inhibition proneness (SIS1 and SIS2), sexual excitation proneness, impact
      of mood on sexuality, and trait measures of depression and anxiety. Age and SIS1
      (inhibition due to threat of performance failure) were strong predictors of ED in
      both gay and heterosexual men. Gay men scored higher on SIS1 whether or not they
      reported ED, consistent with greater concerns about performance failure in gay
      men. Anxiety was predictive of RE, but only in the heterosexual men. If
      replicated in other samples, these differences may reflect a greater importance
      of erectile function in the sexual lives of gay men and greater importance of
      ejaculatory control in heterosexual relationships.

PMID- 15971012
TI  - Unprotected anal intercourse in HIV-positive and HIV-negative gay men: the
      relevance of sexual arousability, mood, sensation seeking, and erectile problems.
AB  - Reduction of unprotected anal intercourse (UAI) in gay men infected with HIV is
      important in preventing further spread of this infection. In previous studies,
      personality trait measures relevant to sexual arousability and the effects of
      anxiety have been shown to relate to UAI in both gay and heterosexual men. Are
      HIV+ gay men similar in these respects or are there other personality-related
      factors that influence their sexual risk taking? This question was addressed
      using a convenience sample of 156 HIV+ gay men and 155 HIV- gay men, matched for
      age and UAI risk. There were no significant differences between these two groups
      on measures of sexual arousability, inhibition of sexual arousal in risky
      situations, sensation seeking, depression and anxiety proneness, or tendency to
      increased sexual interest in negative mood states. HIV+ men were, however, more
      likely to report erectile problems and higher scores on an associated trait
      measure, inhibition of arousal due to threat of performance failure. As this
      association was not anticipated, questions about whether erectile problems
      preceded the seroconversion were not asked. Such problems could be associated
      with reluctance to use condoms, thus increasing the likelihood of seroconversion
      and/or disease transmission. Alternatively, erectile problems could be a
      consequence of HIV infection. In each case, this has implications for prevention.
      The associations among HIV status, erectile problems, and UAI need to be
      specifically addressed in future research.

PMID- 15971013
TI  - Patterns of sexual risk behavior change among sexually transmitted infection
      clinic patients.
AB  - Effective interventions to reduce sexually transmitted infection (STI) risk
      behaviors are most potent in the short term and are not uniformly effective for
      all people. The present study examined patterns of sexual behavior change among
      238 men and 104 women who received risk reduction counseling in a public STI
      clinic and were followed for 9 months with a 1-year retrospective clinic chart
      abstraction for newly diagnosed STI. A two-stage, multivariate cluster analysis
      was performed on four risk behavior difference scores (follow-up - baseline) for
      1-month, 3-month, 6-month, and 9-month follow-up frequencies of unprotected
      vaginal and anal intercourse. Cluster analysis identified three profile
      subgroups: Subgroup 1 had lower levels of risk behavior at all time points;
      Subgroup 2 had significant reductions in risk over time; and Subgroup 3
      demonstrated significant increases in risk over time. Analyses on variables
      external to the cluster analysis found that the three profile subgroups differed
      on numbers of sex partners, substance use, sensation seeking, indicators of risk
      reduction motivation and behavioral skills, and contracting new STI. STI clinic
      patients with varying profiles of sexual behavior change were, therefore,
      differentiated by factors relevant to STI interventions.

PMID- 15971014
TI  - An Internet study of cybersex participants.
AB  - Cybersex is a subcategory of online sexual activities (OSA) and is defined as
      when two or more people are engaging in sexual talk while online for the purposes
      of sexual pleasure and may or may not include masturbation. Cybersex is a growing
      phenomenon with a significant impact on participants but very little research has
      been done on this subject to date. This study is the first to attempt to
      delineate characteristics of those who engage in cybersex. Data were collected
      through an online questionnaire in Swedish, administered through the Swedish web
      portal Passagen.se. Out of the total sample (N = 1828), almost a third, both men
      and women, reported to have engaged in cybersex. A logistic regression analysis
      showed that age, sex, and sexual orientation were important demographic variables
      to consider when investigating cybersex. A comparison of interval data showed
      those engaging in cybersex to have a higher likelihood of spending more time
      online for OSA and having more offline sex partners than those not engaging in
      cybersex.

PMID- 15971015
TI  - Photocopies yield lower digit ratios (2D:4D) than direct finger measurements.
AB  - The ratio between 2nd and 4th digit length (2D:4D) may be a negative correlate of
      prenatal testosterone. This possibility has led to a number of studies of 2D:4D
      and its relationship with sexual orientation and other sex-dependent traits. At
      first, 2D:4D ratio was calculated from measurements made directly on the fingers
      but recently a number of studies have used measurements from photocopies of the
      hands. Here, we compared finger lengths (2D, 3D, 4D, and 5D) and ratios obtained
      from these two measurement techniques. Our sample consisted of 30 homosexual men
      and 50 men and 70 women who were not selected for their sexual orientation. We
      found evidence that (1)2D:4D from photocopies tended to be lower than that from
      direct measurements, (2) there were differences in finger lengths such that 2D
      from photocopies tended to be shorter or equal in length to direct measurements,
      while 4D from photocopies tended to be longer or equal in length to direct
      measurements, (3) the sex differences in 2D:4D tended to be stronger for
      photocopy measurements, and (4) the pattern for length differences across 2D to
      5D appeared to be different for homosexual men compared to men and women
      recruited without regard to sexual orientation. We conclude that there are
      differences in digit ratios obtained from photocopies and direct measurements,
      and these differences arise from length differences recorded from the different
      protocols. Therefore, 2D:4D ratios obtained from photocopies and direct
      measurements should not be combined within one study nor should they be used
      together in comparative studies. We suggest that finger length differences
      between the two techniques could result from the shapes of fat-pads at the tips
      of the fingers and these may be dependent on sex and sexual orientation.

PMID- 15971016
TI  - Digit ratio (2D:4D) in homosexual and heterosexual men from Austria.
AB  - Neurohormonal theories of sexual orientation emphasize the organizational effects
      of testosterone on the developing brain. A recent suggestion, that the ratio of
      the length of the 2nd and 4th digits (2D:4D) is negatively correlated with
      prenatal testosterone, has led to a number of studies of 2D:4D in homosexual and
      heterosexual men and women. The results have been mixed. In comparison to
      heterosexual men, mean 2D:4D in gay men has been reported to be hypermasculinized
      (lower 2D:4D), hypomasculinized (higher 2D:4D), or to show no significant
      difference. Here, we report mean 2D:4D in Austrian homosexual and heterosexual
      men. We found no significant difference between means for homosexual and
      heterosexual 2D:4D, with values for both falling between 0.96 to 0.97. There are
      now 6 reports of 2D:4D in heterosexual and homosexual men. Considering Caucasian
      men, the studies from the United States show low heterosexual mean 2D:4D, and
      homosexual mean 2D:4D is higher or similar to that of heterosexuals. The European
      studies show high heterosexual mean 2D:4D, and comparisons with homosexuals
      reveal the latter to have lower or similar mean 2D:4D to that of heterosexuals.
      We discuss these results in relation to the suggestion that mean 2D:4D in
      heterosexual men differs across populations but mean 2D:4D in homosexuals shows
      less geographical variation (the "uniform mean hypothesis"). It is concluded that
      more data are required to clarify whether or not there is a 2D:4D effect for
      sexual orientation in men.

PMID- 15971017
TI  - A reanalysis of five studies on sexual orientation and the relative length of the
      2nd and 4th fingers (the 2D:4D ratio).
AB  - Five studies have examined the relationship between sexual orientation and the
      relative lengths of the 2nd and 4th fingers (the 2D:4D ratio). Although
      differences have commonly been found between heterosexuals and homosexuals, the
      direction of the difference has not been consistent across studies. The original
      data from all five studies were reanalyzed in a search for possible explanations
      of the discrepancies. Because ethnicity is known to affect the 2D:4D ratio, the
      reanalysis focused on participants who identified themselves as White or
      Caucasian, the ethnic group that was most numerous in all of the studies. Age
      differences did not account for the discrepancies. Differences in variability
      within different groups were minor. One interesting result to emerge from the
      reanalysis was that the 2D:4D ratios for the homosexual groups were relatively
      similar across studies. It was the 2D:4D values for the heterosexual participants
      that varied most, particularly between the USA and the British studies, and these
      were responsible for many of the discrepancies in the conclusions across studies.
      The constancy of the 2D:4D ratio for the White homosexuals did not appear to
      extend to homosexuals of three other ethnicities, and there were also
      subpopulation differences related to right or left hands.

PMID- 15971019
TI  - Genetic and environmental influences on adolescents' perceptions of current
      family environment.
AB  - Previous studies of the genetic and environmental components of the Family
      Environment Scale (FES) have typically reported that scales relating to familial
      acceptance are moderately to strongly genetically influenced while measures of
      control are more environmentally influenced. These reports relied on
      retrospective recall, which is not as reliable as recall of current environment.
      To investigate the genetic contribution to contemporaneous perceptions of one's
      rearing environment, the responses on the FES of 471 17-year-old male twins (141
      complete MZ twin pairs, 73 complete DZ twin pairs, 43 incomplete twin pairs)
      participating in the Minnesota Twin-Family Study (MTFS) were analyzed. Individual
      FES scales were generally modestly to moderately heritable. Unlike previous
      research, we did not find evidence that measures of control/structure were less
      heritable than measures of acceptance/support. These findings support a genetic
      basis of perceptions of one's family environment and indicate that reports of
      control/structure may be more genetically influenced than previously believed
      based on retrospective reports.

PMID- 15971020
TI  - Contributions of genes and environments to stability and change in externalizing
      and internalizing problems during elementary and middle school.
AB  - We examined longitudinally collected behavioral reports by teachers on a unique
      twin sample at the ages of 7, 8, 9, 10, 11, and 12 years. As twin and adoption
      studies implicate the role of genetic influence on behavioral problems found to
      be stable in epidemiological samples, the current study employs a developmental
      behavior genetic model to examine the extent to which genetic and environmental
      contributions to problem behaviors are stable and/or change during development.
      In this sample of 410 monozygotic (MZ) and 354 dizygotic (DZ) twins, MZ twins
      were rated as more similar than DZ twins on average. In general, boys were more
      frequently rated as displaying externalizing behaviors than were girls across
      each of the six observations, while girls' internalizing problems were found not
      to be significantly different from boys'. For both sexes, stability in
      externalizing problem behaviors was due to a single common genetic factor whose
      effects acted pleiotropically at each age in the presence of unique environmental
      influences that were transmitted from age-to-age. Change was largely due to
      uncorrelated age-specific non-shared environmental and additive genetic effects.
      Contributions to stability for internalizing problems were due to age-to-age
      transmission of earlier expressed genetic effects. Change for girls and boys
      internalizing problems were largely due to environmental experiences unique to
      siblings along with uncorrelated age-specific genetic effects. These results
      further inform the notion that individual environments are important factors in
      the etiology of problem behaviors, but suggest that heritable contributions to
      phenotypic stability are largely the same across middle childhood and early
      adolescence. Clinical implications of these findings are discussed.

PMID- 15971021
TI  - Heritability of smoking initiation and nicotine dependence.
AB  - In contrast to other aspects of smoking behavior, little attention has been paid
      to the genetics of nicotine dependence. In this paper, three models (single
      liability dimension, independent liability dimension and combined model) have
      been applied to data on smoking initiation and nicotine dependence (n = 1572
      Dutch twin pairs, mean age 30.5). A combined model best described the data. This
      model postulates a smoking initiation dimension and a nicotine dependence
      dimension, which are not independent. For both males and females, individual
      differences in smoking initiation were explained by genetic (44%), shared
      environmental (51%) and unique environmental (5%) influences. The nicotine
      dependence dimension was influenced only by genetic (75%) and unique
      environmental (25%) factors. The substantial impact of genetic factors on
      nicotine dependence emphasizes the need for further research to localize and
      identify specific genes and pathways involved in nicotine dependence.

PMID- 15971022
TI  - Heritability of selective attention and working memory in preschoolers.
AB  - In this study aspects of selective attention and working memory were tested in a
      large sample of nearly 6-year old monozygotic and dizygotic twin pairs, using a
      computerized test battery (Amsterdam Neuropsychological tasks). In the selective
      attention task the presence of a foil signal (target signal at an irrelevant
      location) resulted in more false alarms than a non-target signal. In the working
      memory task an increase in memory load lead to an increase in response times and
      errors. We analyzed variations in absolute performance parameters (overall speed
      and accuracy) and relative performance parameters (increase in errors and/or
      reaction time). The results showed clear familial resemblances on performance. It
      proved difficult to ascribe these effects to shared genes or to shared
      environment. An exception was memory search rate, which was clearly heritable.

PMID- 15971023
TI  - Heritability of word recognition in middle-aged men varies as a function of
      parental education.
AB  - Although it is of lifelong importance, reading ability is studied primarily in
      children and adolescents. We examined variation in word recognition in 347 middle
      aged male twin pairs. Overall heritability (a2) was 0.45, and shared
      environmental influences (c2) were 0.28. However, parental education moderated
      heritability such that a2 was 0.21 at the lowest parental education level and
      0.69 at the highest level; c2 was 0.52 and 0.00, respectively. This constitutes a
      parental education x environment interaction. The higher heritability was due to
      a decrease in the magnitude of shared environmental factors, rather than an
      increase in the magnitude of genetic factors. Other cognitive studies have
      reported gene x environment interactions, but patterns may differ as a function
      of age or specific cognitive abilities. Our results suggest that shared
      environmental factors in families with low parental education have long-lasting
      effects on word recognition ability, well beyond any critical period for
      developing reading proficiency.

PMID- 15971025
TI  - Memory decline of aging reduced by extracellular superoxide dismutase
      overexpression.
AB  - Extracellular superoxide dismutase (EC-SOD) plays an important role in
      controlling oxidative stress as well as intercellular signaling. In the current
      study, we tested the effect of EC-SOD overexpression over the lifespan of a set
      of mice and their wild-type controls to determine the time scale over which EC
      SOD overexpression might attenuate aging-induced memory impairment. Mice with
      overexpression of EC-SOD and wild-type controls were initially trained on the
      radial-arm maze as young adults (3-5 months) and then retrained during middle age
      (12-14 months) and retested in old age at 27 and 30 months. There was little EC
      SOD effect during the young adult middle age periods. EC-SOD overexpression
      prevented the decline in choice accuracy when the mice were 27-30 months of age.
      The EC-SOD overexpressing mice maintained their performance, while the wild-type
      mice declined to naive levels of performance by 30 months of age. Enhancement of
      EC-SOD activity appears to improve memory performance specifically in aging mice.
      EC-SOD mimetic treatment during the course of aging may hold promise for aging
      induced cognitive impairment.

PMID- 15971024
TI  - Examination of the effect of the polymorphic CGG repeat in the FMR1 gene on
      cognitive performance.
AB  - A CGG repeat sequence located in the 5' untranslated region of the FMR1 gene is
      polymorphic with respect to size and stability of the repeat during parent
      offspring transmission. When expanded to over 200 repeats, the gene is
      hypermethylated and silenced, leading to fragile X syndrome (FXS). Recently,
      alleles with large unmethylated repeat tracts (premutations) have been associated
      with ovarian failure and a late-onset tremor/ataxia syndrome, symptoms unrelated
      to FXS. To further investigate the phenotype consequence of high repeat alleles,
      we have analyzed Wechsler adult intelligence scales-III (WAIS-III) measures on 66
      males and 217 females with a wide range of repeat sizes. Among females only, we
      found that FMR1 repeat size and transcript level significantly explained
      approximately 4% of the variance in the Verbal IQ summary measure, suggesting
      that this polymorphism is one of many factors that influence variation in
      cognitive performance. Because of the well established association of increasing
      repeat size with decreasing age at menopause, we also investigated the
      reproductive stage and use of hormone replacement therapy (HRT) as a covariate to
      model verbal intelligence quotient (VIQ). We found that it explained an
      additional 5% of the variance in VIQ, but did not interact with FMR1 repeat and
      transcript level.

PMID- 15971026
TI  - Genetic variation in male and female reproductive characters associated with
      sexual conflict in Drosophila melanogaster.
AB  - Recent studies have shown that elevated mating, courtship and seminal substances
      affect female fitness negatively in Drosophila melanogaster. It has also been
      shown that males vary with respect to these characters and that male harm to
      females correlates positively with components of male fitness. These results
      suggest that there is sexual conflict over the effect of such male characters. An
      important component of this scenario is that females have evolved
      counteradaptations to male harm, but so far there is limited evidence for this.
      Here I define female resistance as the ability to withstand an increased exposure
      to males. Across 10 genetically differentiated lines of D. melanogaster, I found
      genetic variation among females in the reduction of lifespan that followed from
      exposure to males of different durations. There was also genetic variation among
      males with regards to the degree to which they decrease the lifespan of their
      mates. These results suggest that genetic variation for female ability to endure
      male sexually antagonistic adaptations exists and may play an important role in
      male-female coevolution.

PMID- 15971027
TI  - Growth and behavioral traits in Donaldson rainbow trout (Oncorhynchus mykiss)
      cosegregate with classical major histocompatibility complex (MHC) class I
      genotype.
AB  - Although polymorphism in major histocompatibility complex (MHC) genes has been
      thought to confer populations with protection against widespread decimation by
      pathogens, this hypothesis cannot explain the type of large allelic diversity in
      classical MHC class I (Ia) in rainbow trout. Based on expression of Onmy-UBA (MHC
      class Ia) in trout neurons, we hypothesized that polymorphism in trout class Ia
      may contribute to polymorphism in behavioral traits. The present study examined
      whether polymorphism in Onmy-UBA was associated with behavioral variation in
      Donaldson rainbow trout (Oncorhynchus mykiss) using experiments on food
      competition, lure-catch, fright recovery, diel locomotor activity and activity
      characterized as dominance or aggression. These behavioral traits were
      investigated in fish having Onmy-UBA*401/*401 or *4901/*4901 homozygous, or Onmy
      UBA*401/*4901 heterozygous genotypes (referred to as BB, FF and BF,
      respectively). The BB fish exhibited boldness, aggression, faster growth and
      crepuscular activity, while the FF fish showed little boldness, smaller body
      size, and diurnal activity with no aggressive behavior. The BF fish displayed
      traits intermediary to those of the BB and FF fish. These results are consistent
      with polymorphism in a single MHC class Ia locus driving variation in neural
      circuits, thereby creating behavioral variation in the trout. This is the first
      study in any animal to show a potential correlation between polymorphism in MHC
      class Ia genes with polymorphism of behavioral traits such as aggression.

PMID- 15971028
TI  - DeFries-Fulker analysis of twin data with skewed distributions: cautions and
      recommendations from a study of children's use of verb inflections.
AB  - DeFries-Fulker (DF) analysis is an adaptation of multiple regression that is used
      to estimate heritability of extreme scores (h(g)2) on a dimension. Probands are
      identified as scoring below a cutoff that defines impairment, and one then uses
      regression to predict the scores of co-twins from the proband scores and a term
      that denotes the genetic relationship between twins (1.0 for MZ and 0.5 for DZ
      twins). This paper reports illustrative data and simulations for the situation
      where the dimensional variable shows substantial negative skew. Two types of
      simulation were conducted: in the first, an underlying polygenic liability
      dimension was normally distributed: skewing was introduced by transforming or
      truncating the liability distribution. In the second set of simulations, skewing
      arose because an infrequent defective gene impaired scores. In both sets of
      simulations DF analysis was robust in the face of severe skewing of the data. DF
      analysis can provide two pointers to major gene effects on extreme scores on a
      trait with a skewed distribution: first, group heritability estimates will be
      higher for the original skewed data than for normalised data; second, estimates
      of h(g)2 will increase as the cutoff to identify probands is made more stringent.
      Both these features were seen in data from a test of verb inflections given to
      174 6-year-old twin pairs, suggesting that a single major gene may be implicated
      in causing impaired grammatical development.

PMID- 15971029
TI  - Environmental mediation and the twin design.
AB  - Behavior genetic twin designs are increasingly used to study the effects of a
      measured environment whilst controlling for genetic variation. In this research
      note, we show that, in the context of the classical twin design, (1) when the
      environmental variable is necessarily shared between twins, the notion of
      controlling for genetic influence is logically flawed and (2) when the
      environmental variable varies between twins in the same family, partial control
      for genetic influence is possible, but only if appropriate analytic models are
      used, which is commonly not the case. Based on a simple simulation study,
      recommendations are given as to which methods should be applied and which should
      be avoided.

PMID- 15971030
TI  - Mx scripts library: structural equation modeling scripts for twin and family
      data.
AB  - Structural equation modeling (SEM) provides a flexible tool to carry out genetic
      analyses of family and twin data. The basic model which decomposes the variance
      between and within families for a particular trait into genetic and non-genetic
      components can be generalized to multivariate and/or longitudinal data,
      incorporate sex differences in parameter estimates, and model the effects of
      measured environment, candidate genes or DNA marker data. We introduce a web
      based library (http://www.psy.vu.nl/mxbib) of scripts for uni- and multivariate
      genetic epidemiological analyses, as well as for linkage and genetic association
      tests. The scripts are written to be used with the freely available software
      package Mx and provide a flexible and uniform approach to the analysis of data
      from relatives.

PMID- 15971031
TI  - Endothelial nitric oxide synthase upregulation in the cochlea of the guinea pig
      after intratympanic gentamicin injection.
AB  - Single-shot transtympanic gentamicin therapy has become a popular treatment
      modality for Meniere's disease despite the known possible ototoxic properties of
      this drug. It was shown recently that NO production and iNOS were upregulated
      after gentamicin application, which was interpreted as a possible effect of
      ototoxicity. In this study we analyzed the expression of eNOS after gentamicin
      application to determine a possible correlation of this enzyme with gentamicin
      induced ototoxicity. We compared eNOS expression in gentamicin-treated and non
      treated guinea pigs in the second turn of the cochlea, an area corresponding to
      speech perception in humans. Gentamicin (4 mg) was injected intratympanically
      into the middle ear of guinea pigs ( n =3) and the reduction of the hearing
      threshold level was determined by recording acoustic-evoked potentials (AEP)
      before and 5 days after gentamicin application. Morphological alterations in the
      organ of Corti were analyzed by light and electron microscopy. Gold-labeled anti
      eNOS antibodies were counted in eight different cell areas for quantification of
      eNOS expression. Seven animals were analyzed as controls. After gentamicin
      application, a deterioration of hearing level was observed varying from 10 to 30
      dB. A high degree of vacuolization was identified in the third row of outer hair
      cells. At the subcellular level, the subsurface cisterns in outer hair cells were
      dissociated from the basolateral cell membrane, and the mitochondrial membranes
      were frequently damaged. Statistically significant upregulation of eNOS was
      observed in all cell types analyzed. Depending on the various cell types the
      amount of gold-labeled eNOS antibodies was 2.5 to 5.7 times higher after
      gentamicin application. We observed significant eNOS upregulation after
      gentamicin application in the cochlea, in conjunction with cellular damages and
      decreased hearing.

PMID- 15971032
TI  - Incapacitating hypersensitivity to one's own body sounds due to a dehiscence of
      bone overlying the superior semicircular canal. A case report.
AB  - We present a case study of a 49-year-old patient with an 8-year history of
      hypersensitivity to sound produced by intrinsic but not extrinsic sources.
      Findings that indicated an organic problem were: a supranormal bone conduction
      threshold of -25 to -15 dB HL from 0.25 to 1 kHz with an air-bone gap of 15 to 45
      dB HL, a lower threshold and larger amplitude for vestibular-evoked myogenic
      potentials, eye movement reactions to sound and trunk pitch sway in response to
      sound. Results of immitance audiometry and otoacoustic emission testing were
      within normal limits and indicative of intact middle ear conductance. A high
      resolution CT scan of the temporal bone demonstrated a dehiscence of bone
      overlying the superior semicircular canal. These findings support previous
      research indicating that auditory energy reaches the cochleo-vestibular receptor
      systems more easily via transmission through cerebrospinal fluid than through
      bone. Therefore, a dehiscence of the bone overlying the superior semicircular
      canal may lead to hypersensitivity to intrinsic sound. We recommend that similar
      findings in other patients be followed up with an evaluation of middle ear
      function and the temporal bone with high-resolution CT scan.

PMID- 15971033
TI  - [Evidence based medicine. Wish and reality in routing surgical practice].

PMID- 15971034
TI  - [Injection site abscesses in intravenous drug users. Frequency of associated
      complications related to localisation].
AB  - BACKGROUND: Skin and soft tissue infections are the most frequent cause of
      hospital admissions among intravenous drug users. Associated complications
      include septic arthritis, septic thrombosis and embolisation, peripheral
      ischaemia due to intra-arterial injections, venous and arterial pseudoaneurysms,
      local destruction of adjacent structures, and necrotising fasciitis. METHODS: We
      conducted a retrospective review of the associated complications of 85 patients
      with 130 abscesses treated during 108 hospital stays. RESULTS: The majority of
      abscesses (55%) were located on the lower extremities, where the complication
      rate following injections was significantly higher than in other parts of the
      body (12/71 vs 0/55, P=0.0005). Patients with abscesses on the lower extremities
      had significantly longer hospital stay than those with abscesses on other
      localisations (8.5 days vs 4.2 days, P=0.0005) and therefore were more expensive
      to treat. CONCLUSIONS: Surgeons treating abscesses caused by intravenous drug use
      must be aware of the higher rate of associated complications after injection in
      the lower extremities. Prevention in drug addiction programs could reduce
      complications and costs related to drug use by avoiding injection sites on the
      lower extremities.

PMID- 15971035
TI  - [Significance of occult lymphatic tumor spread in pancreatic cancer].
AB  - PURPOSE: The aim of this study was to determine the frequency and effect on
      prognosis of occult tumor cells in regional lymph nodes judged to be tumor-free
      in conventional histopathology of pancreatic cancer patients. PATIENTS AND
      METHODS: Among 115 patients who underwent pancreatic resection for pancreatic
      (n=84) or distal common bile duct malignancy (n=12) or carcinoma of the papilla
      (n=19), 48 (42%) were staged pN0. Archival paraffin blocks of 271 resected
      regional lymph nodes of 41 pN0 patients were reevaluated for occult tumor cells
      using monoclonal antibody Ber-EP4. Cases with or without isolated tumor cells
      were compared regarding the distribution of various clinicopathological factors.
      RESULTS: Of 41 pN0 patients, 16 (39%) exhibited single Ber-Ep4 immunoreactive
      cells or small cell clusters in at least one lymph node. The occurrence of occult
      tumor cells was not dependent on other clinicopathological factors such as pT
      stage, grading, or curative resection. However, those cells were encountered more
      frequently in common bile duct carcinomas (100%) than in pancreatic (36%) or
      papilla (20%) carcinomas (P=0.009). Occult tumor cells impaired prognosis
      significantly in uni- and multivariate analyses (estimated 5-year survival 53%
      for pN0((i-)) vs 10% for pN0((i+)) and 9% for pN1/N2; P=0.0047). CONCLUSION:
      Occult tumor cells are frequent in apparently tumor-free lymph nodes of
      pancreatic cancer patients and often overlooked in conventional histopathology.
      They are encountered even in limited stages of disease and they impair prognosis,
      which is comparable to that of patients with true lymphatic metastases. Occult
      tumor cells in lymph nodes of pancreatic cancer patients could be used to
      stratify adjuvant therapy.

PMID- 15971036
TI  - [Unclear per anum bleeding during pregnancy].
AB  - A 30-year-old, 7-months pregnant woman presented with per anum bleeding.
      Rectoscopy showed the cause to be a polyp the size of a fingertip 9 cm from the
      anus. Since the bleeding stopped spontaneously and therefore the need for radical
      intervention, and due to the advanced pregnancy stage, no biopsy was done. About
      1 year later, the same patient experienced sharp pains and anal bleeding during
      defecation. A poorly defined neuroendocrine carcinoma was diagnosed. Seeking a
      prognosis optimal for the newborn child, the interdisciplinary decision was made
      for primary surgery with adjuvant chemotherapy. Other options for this malignancy
      during and after pregnancy are also discussed.

PMID- 15971037
TI  - [Progressive ischaemia of the hand caused by aneurysm].
AB  - Arterial aneurysmata of the hand represent a rarity. Post-traumatic aneurysms of
      the ulnaric artery are subsumed under the so-called hypothenaric or hammer
      syndrome. This report describes a 36-year-old patient with a symptomatic aneurysm
      of the superficial palmaric arc distal to the ulnaric artery outside of the Loge
      de Guyon. The branches of the communicating digital arteries were part of the
      aneurysm. Unable to recall any trauma to the left hand, the patient had an
      impaired blood supply to the left second, fourth, and fifth fingers. He
      complained of unpleasant paleness, cold sensation, and pain there. Particularly
      remarkable was the absence of an anastomosis of the superficial and profound
      arterial arcs. The therapy was microsurgical resection of the aneurysm with end
      to-end anastomosis of the superficial palmaric arc and reinsertion of the
      communicating digital arteries 4 and 5. After release of a haematoma, the wound
      healed without any complications and the complaints ceased. The suggested therapy
      concerning a cardiac infarction 5 years prior to the treatment was: 300 mg of
      aspirin for 12 months followed by 100 mg as a permanent medication.

PMID- 15971039
TI  - Cecal volvulus: a rare cause of bowel obstruction in a pediatric patient
      diagnosed pre-operatively by conventional imaging studies.
AB  - Cecal volvulus is an acute surgical condition that is extremely rare in children,
      with a mortality rate of up to 40%. The clinical symptoms are often non-specific,
      and pediatric patients frequently have neurological deficits with associated
      communication difficulties, making the clinical diagnosis extremely challenging.
      Conventional radiographic imaging studies play a key role in the prospective
      diagnosis in children. We report a rare case of cecal volvulus in a 12-year-old
      boy who was diagnosed pre-operatively by abdominal radiographs and a contrast
      enema.

PMID- 15971038
TI  - The recessive potyvirus resistance gene pot-1 is the tomato orthologue of the
      pepper pvr2-eIF4E gene.
AB  - The translation initiation factor 4E (eIF4E) has been implicated in naturally
      occurring resistance to Potato virus Y (PVY) determined by the pvr2 locus in
      pepper (Capsicum annuum). Here, the molecular basis of the recessive resistance
      to PVY and Tobacco etch virus (TEV) controlled by the pot-1 locus in tomato
      (Lycopersicon esculentum; now Solanum lycopersicum) was investigated. On the
      basis of genetic mapping data that indicated that pot-1 and pvr2 are located in
      syntenic regions of the tomato and pepper genomes, the possible involvement of
      eIF4E in pot-1-mediated resistance was assessed. Genetic mapping of members of
      the eIF4E multigenic family in tomato introgression lines revealed that an eIF4E
      locus indeed maps in the same genomic region as pot-1. By comparing eIF4E coding
      sequences between resistant and susceptible Lycopersicon genotypes, a small
      number of polymorphisms that co-segregate with the pot-1 locus were identified,
      suggesting that this gene could be involved in resistance to potyviruses.
      Functional complementation experiments using Potato virus X-mediated transient
      expression of eIF4E from a susceptible genotype in a resistant pepper genotype
      confirmed that a small number of amino acid substitutions in the eIF4E protein
      indeed account for resistance/susceptibility to both the PVY and TEV, and
      consequently that pot-1 and pvr2 are orthologues. Taken together, these results
      support the role of this eIF4E gene as a key component of recessive resistance to
      potyviruses, and validate the comparative genomic approach for the molecular
      characterization of recessive resistance genes.

PMID- 15971040
TI  - [Distal clavicle edema].
AB  - PURPOSE: Distal clavicle marrow edema: frequency, MRI in the early stage and
      macroscopic correlation to the bone marrow distribution and to evaluate frequency
      and diagnostic criteria of a posttraumatic clavicula disorder with an edema
      pattern on MRI. An additional macroscopic study of the clavicle should elucidate
      anatomic peculiarities which could explain the reaction of the distal clavicle.
      MATERIAL AND METHODS: 285 MRI of traumatized patients were analyzed for edema
      pattern of the distal clavicle. Pattern A edema within the clavicle and the
      acromion was distinguished from pattern B edema within the clavicle only.
      Dissection in 20 cadavers should reveal vascular peculiarities and the bone
      marrow distribution within clavicle and acromion or vascular peculiarities.
      RESULTS: In 38 patients (13,3%) we found edema within the distal clavicle.
      Pattern A was found in 28 (9,8%) and pattern B in 10 patients (3,5%). Pattern A
      was usually associated with swelling of the AC joint (27 out of 28). Other
      injuries were not evident. 18 cadavers showed hematopoietic marrow within the
      distal clavicle and fatty marrow within the acromion. CONCLUSION: The distal
      clavicle can frequently react with edema pattern after trauma without evidence
      for another injury. Distinguish in cases with and cases without synovitis of the
      AC joint could have impact on therapy. A peculiar vascular supply of the distal
      clavicle could not be found.

PMID- 15971041
TI  - [Digital teaching archive. Concept, implementation, and experiences in a
      university setting].
AB  - Film-based teaching files require a substantial investment in human, logistic,
      and financial resources. The combination of computer and network technology
      facilitates the workflow integration of distributing radiologic teaching cases
      within an institution (intranet) or via the World Wide Web (Internet). A digital
      teaching file (DTF) should include the following basic functions: image import
      from different sources and of different formats, editing of imported images,
      uniform case classification, quality control (peer review), a controlled access
      of different user groups (in-house and external), and an efficient retrieval
      strategy. The portable network graphics image format (PNG) is especially suitable
      for DTFs because of several features: pixel support, 2D-interlacing, gamma
      correction, and lossless compression. The American College of Radiology (ACR)
      "Index for Radiological Diagnoses" is hierarchically organized and thus an ideal
      classification system for a DTF. Computer-based training (CBT) in radiology is
      described in numerous publications, from supplementing traditional learning
      methods to certified education via the Internet. Attractiveness of a CBT
      application can be increased by integration of graphical and interactive elements
      but makes workflow integration of daily case input more difficult. Our DTF was
      built with established Internet instruments and integrated into a heterogeneous
      PACS/RIS environment. It facilitates a quick transfer (DICOM_Send) of selected
      images at the time of interpretation to the DTF and access to the DTF application
      at any time anywhere within the university hospital intranet employing a standard
      web browser. A DTF is a small but important building block in an institutional
      strategy of knowledge management.

PMID- 15971042
TI  - [MR urography: principles, examination techniques, indications].
AB  - MR urography is an evolving and promising technique in the evaluation of the
      urinary tract. MR urography is currently considered the method of choice for
      imaging of the renal parenchyma and the collecting systems in patients who cannot
      undergo routine radiographic studies such as pregnant women, pediatric patients,
      patients allergic to iodinated contrast agents, or patients with impaired renal
      function. The future development of MR urography in terms of functional,
      cellular, and molecular imaging is presently the subject of research. The ability
      of MR imaging to provide quantitative functional information (e.g., on blood
      flow, perfusion, glomerular filtration rate, and excretion as well as urine
      drainage) in addition to morphologic assessment of the parenchyma and the
      collecting system could lead to a single, "all-in-one approach" examination
      technique.

PMID- 15971043
TI  - Analysis of sorption and bioavailability of different species of mercury on model
      soil components using XAS techniques and sensor bacteria.
AB  - The present work studies the adsorption behaviour of mercury species on different
      soil components (montmorillonite, kaolinite and humic acid) spiked with CH3HgCl
      and CH3HgOH at different pH values, by using XAS techniques and bacterial mercury
      sensors in order to evaluate the availability of methyl mercury on soil
      components. The study details and discusses different aspects of the adsorption
      process, including sample preparation (with analysis of adsorbed methyl mercury
      by ICP-OES), the various adsorption conditions, and the characterization of
      spiked samples by XAS techniques performed at two synchrotron facilities (ESRF in
      Grenoble, France and HASYLAB in Hamburg, Germany), as well as bioavailability
      studies using mercury-specific sensor bacteria. Results show that XAS is a
      valuable qualitative technique that can be used to identify the bonding character
      of the Hg in mercury environment. The amount of methyl in mercury adsorbed to
      montmorillonite was pH-dependent while for all soil components studied, the bond
      character was not affected by pH. On the other hand, clays exhibited more ionic
      bonding character than humic acids did with methyl mercury. This interaction has
      a higher covalent character and so it is more stable for CH3HgOH than for
      CH3HgCl, due to the higher reactivity of the hydroxyl group arising from the
      possible formation of hydrogen bonds. The bioavailability of methyl mercury
      adsorbed to montmorillonite, kaolinite and humic acids was measured using
      recombinant luminescent sensor bacterium Escherichia coli MC1061 (pmerBR(BS)luc).
      In case of contact exposure (suspension assays), the results showed that the
      bioavailability was higher than it was for exposure to particle-free extracts
      prepared from these suspensions. The highest bioavailability of methyl mercury
      was found in suspensions of montmorillonite (about 50% of the total amount),
      while the bioavailabilities of kaolinite and humic acids were five times lower
      (about 10%). The behaviour of methyl mercury in the presence of montmorillonite
      could be explained by the more ionic bonding character of this system, in
      contrast to the more covalent bonding character observed for humic acids. Thus,
      XAS techniques seem to provide promising tools for investigating the mechanisms
      behind the observed bioavailabilities of metals in various environmental
      matrices, an important topic in environmental toxicology.

PMID- 15971044
TI  - Simultaneous determination of DTPA, EDTA, and NTA by UV-visible spectrometry and
      HPLC.
AB  - In this study, UV-visible spectrophotometry (UV-Vis) and high-performance liquid
      chromatography (HPLC) were used for simultaneous analysis of chelating agents
      diethylenetriamine pentaacetic acid (DTPA), ethylenediamine tetraacetic acid
      (EDTA), and nitrilotriacetic acid (NTA), as their metal chelates in dishwashing
      detergents, natural waters, and pulp mill water. The total amounts of the
      chelating agents in dishwashing detergents were verified by potentiometric
      titration with Fe(III) solution. Nickel(II) chelates were determined by UV-Vis
      and iron(III)chelates by HPLC and titration. Recoveries of DTPA, EDTA, and NTA
      from a standard mixture of analytes by UV-Vis were 107+/-7, 101+/-12 and 94+/
      13%, respectively, and the recovery of the total amount of complexing agents was
      99+/-4%. The limits of detection for DTPA, EDTA, and NTA were 667, 324, and 739
      micromol L(-1), respectively. In HPLC measurements the optimized mobile phase
      contained 0.03 mol L(-1) sodium acetate, 0.002 mol L(-1) tetrabutylammonium
      bromide, and 5% methanol at pH 3.15 and the detection was by UV-Vis detection at
      254 nm. All three complexing agents could be separated from each other in a
      simultaneous analysis in less than 5 min. The limits of detection were 0.34,
      0.27, and 0.62 micromol L(-1) for DTPA, EDTA, and NTA, respectively. The total
      amounts of the analytes measured in the dishwashing detergents by the three
      techniques were found to be highly comparable (ANOVA: F=0.04, P=0.96). R(2)
      values were 0.99 for EDTA, 0.99 for NTA, and 0.99 for all the results when UV-Vis
      and HPLC determinations were compared using regression lines. The UV-Vis and HPLC
      methods were proved to be viable also for analyses of natural and pulp mill
      waters. The absence of matrix interferences was verified by the standard addition
      technique.

PMID- 15971045
TI  - Application of a chemometric method for simultaneous determination of
      acetaminophen and diclofenac in content-uniformity and drug-dissolution studies.
AB  - A new, repeatable, and rapid method has been developed for resolution of binary
      mixtures of acetaminophen and diclofenac with minimum sample pretreatment and
      without separation of the analytes. The method, based on the PLS1 processing of
      absorbance data in the UV region, was successfully used for quantification of the
      drug content of three tablet preparations. The results obtained were in good
      agreement with HPLC recovery data. The method also enabled determination of drug
      dissolution profiles of these commercial tablets, by simultaneous determination
      of both analytes during the dissolution test.

PMID- 15971046
TI  - [Renal neurilemoma--a rare differential diagnosis of renal tumors].
AB  - Neurilemomas originate from the Schwann cells of nerve sheaths. They can occur
      ubiquitously as benign or malign variants. Renal neurilemomas are extremely rare.
      Imaging does not allow a certain diagnosis. Complete tumor resectioning is the
      only curative therapy. Effective conservative treatment is not known.
      Histological criteria of renal neurilemoma are: mesenchymal, spindle cell,
      capsulated tumor intensely positive to S-100 antiserum. Epithelial markers do not
      react.

PMID- 15971047
TI  - [Complicated urethral reconstruction in the adult and adult and infant males].
AB  - The urethral reconstruction is a challenge in the adult, but even more in infant
      and young male patients. Good knowledge of the anatomy of the penis (blood supply
      and the course of the nerve fibers) with the availability of microsurgery
      suturing and instruments improved the outcome significantly. The growing
      knowledge opened the possibility to reconstruct complicate strictures with
      grafts. The buccal mucosa flap is one of those improvements, which made a
      tremendous impact to have a successful outcome. Recently we looked into the
      outcome of urethral reconstruction of long urethral strictures by using a buccal
      mucosa only flap. We used a modified technique for hypospadias repair to
      reconstruct coronar or subcoronar defects by meatal mobilization (MEMO). In cases
      with a long urethral stricture the success rate was over 90% with a mean follow
      up of 16 months. In all children the outcome with the MEMO-technique was
      successful without any major complication with a mean follow-up of 12.5 months.

PMID- 15971048
TI  - [Cryopreserved human sperm deposits: usability after decades of storage].
AB  - To determine the effect of long-term storage on cryopreserved human sperm, 238
      individual samples from 34 cryopreserved sperm deposits that had been collected
      between 1976 and 1989 were evaluated at regular intervals. The material was from
      34 patients, 18 of whom suffered from underlying malignant disease. Every 3 years
      a sample from each deposit was thawed for microscopic analysis. During the course
      of the storage period limited to a maximum of 21 years, all ejaculate parameters
      had deteriorated in comparison to fresh semen. Quantitative motility was the most
      sensitive parameter with a decrease of ca. 80%. Sperm density decreased hardly at
      all. The parameters of the criteria investigated did not decrease linearly or
      proportionally with the storage duration, but rather more directly after the
      freezing process or within the first 3 years. These changes became increasingly
      smaller as the storage time lengthened. Almost all of the deposits exhibited
      adequate quality at all times during storage. Consequently, 21-year permanent
      frozen storage in liquid nitrogen is safe regarding aspects of spermatology.

PMID- 15971049
TI  - [Proof of endolymphatic hydrops].

PMID- 15971050
TI  - [Auditory processing disorder versus attention deficit/hyperactivity disorder. A
      dysfunction complex or different entities?].
AB  - BACKGROUND: It has been suggested that auditory processing disorders (APD) and
      attention deficit/hyperactivity disorders (ADHD) may be the same entity with
      slightly differing symptoms. For testing this theory we compared parents' ratings
      of APD and ADHD behavioural characteristics. METHODS: A retrospective study was
      carried out with parents rating 312 children (113 girls and 199 boys; 6.0-9.11
      years old, nonverbal intelligence IQ 95 or above) using APD and ADHD
      questionnaires. RESULTS: Significant, albeit weak correlations between several
      APD and ADHD subscale scores were found. Correlations between selective listening
      and attention behaviours approximated clinical relevance (rho >0.4). Factor
      analysis revealed two factors with APD behaviour loading on one and ADHD
      behaviour on a second different factor. Using a categorical approach, it appears
      that ADHD children have significantly more APD problems than children without
      ADHD. DISCUSSION: These data are consistent with the hypothesis that APD and ADHD
      overlap partly while still being distinct entities. In addition to dimensional
      aspects, the parents' rating may provide a guideline for establishing a diagnosis
      based on categorical distinctions.

PMID- 15971051
TI  - [Acute chest pain].
AB  - Acute chest pain is the leading cause of hospital admissions worldwide and
      absorbs extensive financial and hospital resources for diagnosis and management.
      A missed diagnosis of acute myocardial infarction is still associated with a poor
      outcome and represents one of the most common reasons for lawsuits in the USA.
      The present article gives a summary on the features of cardiac and non-cardiac
      chest pain, provides an overview of diagnostic algorithms, and points out the
      important differential diagnoses.

PMID- 15971052
TI  - [Acute cerebral circulation problems].
AB  - Acute stroke is the third most common cause of death and also the most common
      cause of permanent disability in industrialized countries. Ischemic stroke is
      caused by occlusion of a cerebral artery leading to a critical reduction in brain
      perfusion in the respective brain area (penumbra). Most acute stroke treatment
      strategies are based on the penumbra concept: attaining rapid and persistent
      reperfusion is followed by the protection of critically ischemic and not yet
      infarcted (penumbral) tissue by, e.g., neuroprotection. Examination of the acute
      stroke patient includes a brief history, neurostatus and imaging (CT or MRI) for
      the exclusion of intracerebral hemorrhage. The diagnostic standard is CT; modern
      stroke MRI protocols provide an improved selection in later time windows.
      Intravenous thrombolysis with rt-PA within 3 h of symptom onset is the only
      approved therapy with a proven significant benefit for the patient. The effect is
      smaller but still significant if treatment occurs up to 4.5 h, and may still be
      present in MRI selected patients up to 9 h. More aggressive forms of therapy
      include interventional reperfusion techniques and therapy of malignant MCA
      infarction such as hemicraniectomy and hypothermia, which at present, however,
      are not routine and are only performed in specialized centers.

PMID- 15971053
TI  - Uterine leiomyoma among women who conceived following fertility treatment.
AB  - OBJECTIVE: The objective was to determine if uterine leiomyoma increases the risk
      of cesarean section (CS) among women who conceived following fertility treatment.
      STUDY DESIGN: The study population consisted of all women who conceived after
      fertility treatment with singleton gestation and who delivered between the years
      1988 and 1999 in the Soroka University Medical Center. A comparison was performed
      between patients with and without uterine leiomyomas. The Mantel-Haenszel
      procedure was used to obtain the weighted odds ratio (OR) for CS, while
      controlling for confounding variables. RESULTS: During the study period 1,995
      women conceived following fertility treatment. Of these, 63 patients had uterine
      leiomyomas (3.2%). Women treated for fertility with uterine leiomyomas had
      statistically significant higher rates of CS than those without uterine
      leiomyomas (61.9% vs. 28.1%, OR=4.2, 95% CI 2.4-7.2; P<0.001). Stratified
      analysis (the Mantel-Haenszel technique) was used to control for possible
      confounders, such as gestational diabetes, hypertensive disorders, maternal age,
      failure of labor to progress, placental abruption, malpresentation, hydramnios,
      oligohydramnios, and a previous CS. None of those variables changed the
      significant association or explained the higher incidence of CS in the uterine
      leiomyoma group. CONCLUSIONS: Uterine leiomyoma is an independent risk factor for
      CS among women who conceived following fertility treatment.

PMID- 15971054
TI  - Neuronal intranuclear inclusion disease in a horse.
AB  - Neuronal intranuclear inclusion disease (NIID) is reported in a 16-year-old Pure
      Spanish breed female horse suffering from progressive ataxia and motor
      deficiencies. The neuropathological study revealed NIIs throughout the central
      nervous system, although mainly in the brain stem and spinal cord. This
      distribution did not correlate with neuron loss, which was marked in the
      hippocampus and moderate in the neocortex, particularly in the occipital cortex.
      As in humans, NIIs in the horse were hyaline autofluorescent inclusions composed
      of non-membrane-bound aggregates of filaments and fine granules. NIIs were
      stained with anti-ubiquitin and anti-clusterin antibodies. In addition, NIIs were
      stained with antibodies raised against subunits of the 19S and PA28, but not of
      the 20S, components of the proteasome. These observations indicate similarities
      between NIID in humans and horses, and suggest that clusterin and abnormal
      ubiquitin-proteasomal expression participate in NII formation.

PMID- 15971055
TI  - Argyrophilic grains are not always argyrophilic--distinction from neurofibrillary
      tangles of diffuse neurofibrillary tangles with calcification revealed by
      comparison between Gallyas and Campbell-Switzer methods.
AB  - Silver staining profiles of argyrophilic grains (AGs) and of neurofibrillary
      tangles (NFTs) of diffuse neurofibrillary tangles with calcification (DNTC,
      collectively as DNTC-NFTs) were examined for their relation to tau- and ubiquitin
      like immunoreactivity (IR). Pairs of mirror sections were triple-fluorolabeled
      with an anti-PHF tau (AT8) antibody, an anti-ubiquitin antibody and thiazin red
      (TR), a fluorochrome that identifies fibrillary structures such as NFTs of
      Alzheimer's disease (AD). One of the paired sections was subsequently stained
      with Gallyas method (GAL), and the other with Campbell-Switzer method (CS).
      Comparison of the same microscopic field on the paired fluorolabeled sections,
      subsequently silver-stained with either GAL or CS enabled the determination of
      five different profiles of each structure: AT8-IR, ubiquitin-like-IR, affinity to
      TR, argyrophilia with GAL or CS staining. AGs, mainly composed of four-repeat
      (4R) tau, were argyrophilic with GAL but not with CS, and their affinity to TR
      and ubiquitin-like-IR was not intense. This staining profile of AGs is identical
      with those of tau-positive structures in the cortex of progressive supranuclear
      palsy/corticobasal degeneration, both composed of 4R tau. This selective affinity
      of AGs to GAL is in sharp contrast with Pick bodies, composed of three-repeat
      (3R) tau, that are positive for CS but not for GAL, as we reported previously.
      This contrast is explainable if the argyrophilia with CS is related to deposits
      containing 3R tau, while that with GAL is linked to those containing 4R tau.
      Indeed, DNTC-NFTs, that contain both 3R and 4R tau, were argyrophilic with CS and
      GAL, and their affinity to TR and ubiquitin-like-IR were consistent, as we
      reported previously for NFTs of AD and of Down's syndrome, both similarly
      composed of 3R and 4R tau. Taken together, differences in molecular composition
      of tau protein in these deposits are linked to their argyrophilic properties
      dependent on the staining method in these sporadic tauopathies. Although
      explanations for these empirical differences are not yet available, awareness of
      this clear distinction is potentially of diagnostic and pathological
      significance.

PMID- 15971056
TI  - Overexpression of heat shock proteins in pallido-nigral axonal spheroids of
      nonhuman aged primates.
AB  - The occurrence of spheroids has been described in the globus pallidus (GP) and
      substantia nigra pars reticulata (SNr) of aged rhesus monkeys. Opinions vary as
      to the origin of spheroids. Ultrastructural and immunohistochemical analysis
      suggested that spheroids originate from degenerating axons or astroglia. In the
      present study, we have investigated the GP and SNr of aged monkeys (Macaca
      fascicularis and Macaca mulatta). Although immunoreactive for microtubule
      associated protein (MAP) 1A, tau, amyloid precursor protein, synaptophysin and
      phosphorylated neurofilament, spheroids were not immunoreactive for MAP1B and
      MAP2. We confirmed the axonal nature of pallido-nigral spheroids in aged rhesus
      monkeys. Pallido-nigral spheroids have been reported to overexpress stress
      proteins, such as ubiquitin, alphaB-crystallin, and heat shock protein (Hsp) 27.
      We further evaluated the expression of Hsps in pallido-nigral spheroids. As well
      as being intensely immunoreactive for ubiquitin, alphaB-crystallin, Hsp27, and
      Hsp70, spheroids were immunoreactive for Hsp32 (heme oxygenase-1), Hsp40, Hsp60,
      and Hsp90. On the basis of these findings, we speculate that Hsp32-immunoreactive
      spheroids might be expressed as an oxidative stress response. Induction of other
      Hsps might play a role in protection of axons from the aggregation of
      neurofilament, MAPs and other proteins, and failure to protect degenerating axons
      might result in their proteolysis by the ubiquitin-proteasome system.

PMID- 15971057
TI  - An autopsy case of early ("minimal change") olivopontocerebellar atrophy
      (multiple system atrophy-cerebellar).
AB  - We report a 57-year-old woman with multiple system atrophy (MSA) of 15-month
      duration. The patient developed dysarthria, followed by impaired balance of gait,
      mild limb ataxia, and saccadic eye movement. A postmortem examination performed
      after she was found dead in a bathtub revealed neuronal loss restricted to the
      olivopontocerebellar system, being more severe in the pontine nucleus. Mild
      neuronal loss was also found in the anterior vermis and inferior olivary nucleus.
      Alpha-synuclein immunohistochemistry demonstrated widespread occurrence of glial
      cytoplasmic inclusions in the central nervous system, which were more numerous in
      the pontine base and cerebellar white matter. In contrast, neuronal alpha
      synuclein accumulation was confined to the pontine and inferior olivary nuclei.
      The number of neuronal intranuclear inclusions was much higher than that of
      neuronal cytoplasmic inclusions. Moreover, alpha-synuclein accumulation was more
      severe in the neurites than in the cytoplasm or nucleus. This case demonstrates
      the early pattern of brain pathology in MSA-cerebellar (olivopontocerebellar
      atrophy).

PMID- 15971058
TI  - Intracerebroventricular administration of melanotan II increases insulin
      sensitivity of glucose disposal in mice.
AB  - AIMS/HYPOTHESIS: The present study was conducted to evaluate the effects of
      central administration of melanotan II (MTII), a melanocortin-3/4 receptor
      agonist, on hepatic and whole-body insulin sensitivity, independent of food
      intake and body weight. METHODS: Over a period of 24 h, 225 ng of MTII was
      injected in three aliquots into the left lateral ventricle of male C57Bl/6 mice.
      The animals had no access to food. The control group received three injections of
      distilled water. Whole-body and hepatic insulin sensitivity were measured by
      hyperinsulinaemic-euglycaemic clamp in combination with [(3)H]glucose infusion.
      Glut4 mRNA expression was measured in skeletal muscle. RESULTS: Plasma glucose
      and insulin concentrations under basal and hyperinsulinaemic conditions were
      similar in MTII- and placebo-treated mice. Endogenous glucose production (EGP)
      and glucose disposal in the basal state were significantly higher in MTII-treated
      mice than in the control group (71+/-22 vs 43+/-12 micromol.min(-1).kg(-1),
      p<0.01). During hyperinsulinaemia, glucose disposal was significantly higher in
      MTII-treated mice (151+/-20 vs 108+/-20 micromol.min(-1).kg(-1), p<0.01). In
      contrast, the inhibitory effect of insulin on EGP was not affected by MTII
      (relative decrease in EGP: 45+/-27 vs 50+/-20%). Glut4 mRNA expression in
      skeletal muscle was significantly increased in MTII-treated mice (307+/-94 vs
      100+/-56%, p<0.01). CONCLUSIONS/INTERPRETATION: Intracerebroventricular
      administration of MTII acutely increases insulin-mediated glucose disposal but
      does not affect the capacity of insulin to suppress EGP in C57Bl/6 mice. These
      data indicate that central stimulation of melanocortin-3/4 receptors modulates
      insulin sensitivity in a tissue-specific manner, independent of its well-known
      impact on feeding and body weight.

PMID- 15971059
TI  - Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early
      treatment?
AB  - Autopsy studies have shown that atherosclerosis begins in adolescence in
      otherwise healthy individuals, and imaging techniques have shown that
      atherosclerosis develops earlier and is more prevalent in children with diabetes
      than in age-matched healthy controls. Cardiovascular disease has now overtaken
      diabetic nephropathy as the leading cause of premature mortality in young adults
      with diabetes, and the emphasis on disease prevention has accordingly shifted to
      a younger age group. The majority of children and adolescents with diabetes have
      suboptimal blood glucose control, and this contributes to accelerated arterial
      disease in this age group. Other conventional risk factors for coronary heart
      disease also need to be considered and treated aggressively. Effective early
      prevention of cardiovascular disease will involve lifestyle modification and full
      implementation of existing treatment guidelines, and large-scale prospective
      studies will be needed to establish the risks and benefits of early
      pharmacological intervention in children and adolescents.

PMID- 15971060
TI  - Urinary sodium and potassium excretion and the risk of type 2 diabetes: a
      prospective study in Finland.
AB  - AIMS/HYPOTHESIS: No previous studies on the association between salt intake and
      the risk of type 2 diabetes have been reported. The aim of this study was to
      assess whether high salt intake, measured by 24-h urinary sodium excretion, is an
      independent risk factor for type 2 diabetes. METHODS: We followed prospectively
      932 Finnish men and 1,003 women aged 35-64 years with complete data on 24-h
      urinary sodium and potassium excretion and other study parameters. Hazard ratios
      for the incidence of type 2 diabetes were estimated for different levels of 24-h
      urinary sodium and potassium excretion. RESULTS: During a mean follow-up of 18.1
      years, there were 129 incident cases of type 2 diabetes. The multivariate
      adjusted (age, sex, study year, body mass index, physical activity, systolic
      blood pressure, antihypertensive drug treatment, education, smoking and coffee,
      alcohol, fruit, vegetable, sausage, bread and saturated fat consumption) hazard
      ratio for diabetes for the highest vs combined lower quartiles of 24-h urinary
      sodium excretion was 2.05 (95% CI, 1.43-2.96). This positive association
      persisted in non-obese and obese subjects, in normotensive and hypertensive
      subjects, as well as in men and women. Potassium excretion was not associated
      with the risk of type 2 diabetes. CONCLUSIONS/INTERPRETATION: High sodium intake
      predicted the risk of type 2 diabetes, independently of other risk factors
      including physical inactivity, obesity and hypertension. These results provide
      direct evidence of the harmful effects of high salt intake in the adult
      population, although the confounding effect of other dietary factors cannot be
      fully excluded.

PMID- 15971061
TI  - A prospective study of lipoprotein(a) and risk of coronary heart disease among
      women with type 2 diabetes.
AB  - AIMS: We examined the association between lipoprotein (Lp)(a) and CHD among women
      with type 2 diabetes. METHODS: Of 32,826 women from the Nurses' Health Study who
      provided blood at baseline, we followed 921 who had a confirmed diagnosis of type
      2 diabetes. RESULTS: During 10 years of follow-up (6,835 person-years), we
      documented 122 incident cases of CHD. After adjustment for age, smoking, BMI,
      glycosylated HbA(1)c, triglycerides (TGs), high-density lipoprotein cholesterol,
      low-density lipoprotein cholesterol and other cardiovascular risk factors, the
      relative risk (RR) comparing extreme quintiles of Lp(a) was 1.95 (95% CI 1.07
      3.56). The association was not appreciably altered after further adjustment for
      apolipoprotein B(100) or several inflammatory biomarkers. Increasing levels of
      Lp(a) were associated with lower levels of TGs. The probability of developing CHD
      over 10 years was higher among diabetic women with substantially higher levels of
      both Lp(a) (>1.07 micromol/l) and TGs (>2.26 mmol/l) than among diabetic women
      with lower levels (22 vs 10%, p log-rank test=0.049). Diabetic women with a
      higher level of only Lp(a) or TGs had a similar (14%) risk. In a multivariate
      model, diabetic women with higher levels of Lp(a) and TGs had an RR of 2.46 (95%
      CI 1.21-5.01) for developing CHD, as compared with those with lower levels of
      both biomarkers (p for interaction=0.413). The RRs for women with a higher level
      of either Lp(a) (RR=1.22, 95% CI 0.77-1.92) or TGs (RR=1.39, 95% CI 0.78-2.42)
      were comparable. CONCLUSIONS/INTERPRETATION: Increased levels of Lp(a) were
      independently associated with risk of CHD among diabetic women.

PMID- 15971062
TI  - Vitamin D and diabetes.
AB  - Vitamin D deficiency predisposes individuals to type 1 and type 2 diabetes, and
      receptors for its activated form-1alpha,25-dihydroxyvitamin D3-have been
      identified in both beta cells and immune cells. Vitamin D deficiency has been
      shown to impair insulin synthesis and secretion in humans and in animal models of
      diabetes, suggesting a role in the development of type 2 diabetes. Furthermore,
      epidemiological studies suggest a link between vitamin D deficiency in early life
      and the later onset of type 1 diabetes. In some populations, type 1 diabetes is
      associated with certain polymorphisms within the vitamin D receptor gene. In
      studies in nonobese diabetic mice, pharmacological doses of 1alpha,25
      dihydroxyvitamin D3, or its structural analogues, have been shown to delay the
      onset of diabetes, mainly through immune modulation. Vitamin D deficiency may,
      therefore, be involved in the pathogenesis of both forms of diabetes, and a
      better understanding of the mechanisms involved could lead to the development of
      preventive strategies.

PMID- 15971063
TI  - Voltage-gated calcium and Ca2+-activated chloride channels and Ca2+ transients:
      voltage-clamp studies of perfused and intact cells of Chara.
AB  - The voltage-clamp technique was used to study Ca(2+) and Cl(-) transient currents
      in the plasmalemma of tonoplast-free and intact Chara corallina cells. In
      tonoplast-free cells [perfused medium with ethylene glycol bis(2-aminoethyl
      ether)tetraacetic acid] long-term inward and outward currents through Ca channels
      consisted of two components: with and without time-dependent inactivation. The
      voltage dependence of the Ca channel activation ratio was found to be sigmoid
      shaped, with about -140-mV activation threshold, reaching a plateau at V>50 mV.
      As the voltage increased, the characteristic activation time decreased from
      approximately 10(3) ms in the threshold region to approximately 10 ms in the
      positive region. The positive pulse-activated channels can then be completely
      deactivated, which is recorded by the Ca(2+) tail currents, at below-threshold
      negative voltages with millisecond-range time constants. This tail current is
      used for fast and brief Ca(2+) injection into tonoplast-free and intact cells, to
      activate the chloride channels by Ca(2+) . When cells are perfused with EDTA
      containing medium in the presence of excess Mg(2+), this method of injection
      allows the free submembrane Ca(2+) concentration, [Ca(2+)](c), to be raised
      rapidly to several tens of micromoles per liter. Then a chloride component is
      recorded in the inward tail current, with the amplitude proportional to [see
      text]. When Ca(2+) is thus injected into an intact cell, it induces an inward
      current in the voltage-clamped plasmalemma, having activation-inactivation
      kinetics qualitatively resembling that in EDTA-perfused cells, but a considerably
      higher amplitude and duration (approximately 10 A m(-2) and tau(inact)~0.5 s at 
      200 mV). Analysis of our data and theoretical considerations indicate that the
      [Ca(2+)](c) rise during cell excitation is caused mainly by Ca(2+) entry through
      plasmalemma Ca channels rather than by Ca(2+) release from intracellular stores.

PMID- 15971064
TI  - Non-traumatic cortical subarachnoid haemorrhage: diagnostic work-up and
      aetiological background.
AB  - Only 15% of all subarachnoid haemorrhages (SAHs) are not of aneurysmal origin.
      Among those, circumscribed SAHs along the cortical convexity are rare and have
      only been described in singular case reports so far. Here, we present a
      collection of 12 cases of SAH along the convexity, of non-traumatic origin. Over
      a period of 10 years, 12 cases of circumscribed SAH along the convexity were
      identified at our clinic. The clinical presentations, neuroradiological SAH
      characteristics, further diagnostic work-up to identify the underlying
      aetiologies, the therapy and clinical outcome were analysed. The patients' chief
      complaints were unspecific cephalgia, focal or generalised seizures and focal
      neurological deficits. Typical signs of basal SAH, such as nuchal rigidity,
      thunderclap-headache or alteration of consciousness, were rare. Magnetic
      resonance imaging (MRI) and digital subtraction angiography (DSA) revealed
      different aetiologies, namely postpartal posterior encephalopathy (three),
      cerebral vasculitis (two), dural sinus thrombosis (two), cortical venous
      thrombosis (one), intracerebral abscesses (one) and cerebral cavernoma (one). Two
      cases remained unresolved. Treatment of the underlying disease and symptomatic
      medication led to good clinical outcome in almost all cases. On the basis of
      these findings, we demonstrate that the clinical presentation, localisation and
      aetiology of cortical SAH differ clearly from other SAHs. A diagnostic work-up
      with MRI and eventually DSA is essential. Mostly, the causative disease can be
      identified, and specific treatment allows a favourable outcome.

PMID- 15971065
TI  - The safety and efficacy of stapled hemorrhoidectomy in the treatment of
      hemorrhoids: a systematic review and meta-analysis of ten randomized control
      trials.
AB  - AIMS: The objective of this study was to compare the safety and efficacy outcomes
      of stapled hemorrhoidectomy (PPH) with Milligan-Morgan hemorrhoidectomy (MMH) in
      the treatment of severe hemorrhoids. METHODS: A meta-analysis pooled the effects
      of the safety and efficacy outcomes on PPH, and MMH in ten randomized control
      trials was presented using a fixed effects model or a random effects model (via
      RevMan Version 4.2). RESULTS: There was reasonably clear evidence in favor of PPH
      for operating time, length of hospital stay, pain, anal discharge, and patient
      satisfaction. However, skin tags and prolapse occurred at higher rates in the PPH
      group. PPH was not more superior than MMH as to postoperative bleeding, urinary
      retention, difficulty in defecating, anal fissure and stenosis, sphincter damage,
      resumption of normal activities, incontinence, pruritus, anal resting and squeeze
      pressures, and analgesia. CONCLUSIONS: PPH may be at least as safe as MMH.
      However, the efficacy of PPH compared with MMH could not be determined
      absolutely. More rigorous studies with longer follow-up periods and larger sample
      sizes need to be conducted.

PMID- 15971066
TI  - Does lignin modification affect feeding preference or growth performance of
      insect herbivores in transgenic silver birch (Betula pendula Roth)?
AB  - Transgenic silver birch (Betula pendula Roth) lines were produced in order to
      modify lignin biosynthesis. These lines carry COMT (caffeate/5-hydroxyferulate O
      methyltransferase) gene from Populus tremuloides driven by constitutive promoter
      35S CaMV (cauliflower mosaic virus) or UbB1 (ubiquitin promoter from sunflower).
      The decreased syringyl/guaiacyl (S/G) ratio was found in stem and leaf lignin of
      35S CaMV-PtCOMT transgenic silver birch lines when compared to non-transformed
      control or UbB1-PtCOMT lines. In controlled feeding experiments the leaves of
      transgenic birch lines as well as controls were fed to insect herbivores common
      in boreal environment, i.e., larvae of Aethalura punctulata, Cleora cinctaria and
      Trichopteryx carpinata (Lepidoptera: Geometridae) as well as the adults of birch
      leaf-feeding beetles Agelastica alni (Coleoptera: Chrysomelidae) and Phyllobius
      spp. (Coleoptera: Curculionidae). The feeding preferences of these herbivores
      differed in some cases among the tested birch lines, but these differences could
      not be directly associated to lignin modification. They could as well be
      explained by other characteristics of leaves, either natural or caused by
      transgene site effects. Growth performance of lepidopteran larvae fed on
      transgenic or control leaves did not differ significantly.

PMID- 15971067
TI  - The effects of attention and handedness on coordination dynamics in a bimanual
      Fitts' law task.
AB  - Two experiments were conducted to investigate the effects of attention and
      handedness on bimanual coordination in the context of a dynamical model of
      coordinated movements. Participants performed a bimanual, rhythmic Fitts' law
      task in which the relative amount of attention directed to each task was
      manipulated by the relative difficulty associated with the pair of targets that
      each hand tapped. In both experiments, participants tended to lead with their
      preferred hand. The effects of attention, though, were mixed, which suggested
      that there was a combined effect of an attentional asymmetry and an asymmetry in
      the hands' uncoupled frequency, both of which are captured in the dynamical
      model.

PMID- 15971069
TI  - Familial Mediterranean fever and mesangial proliferative glomerulonephritis:
      report of a case and review of the literature.
AB  - In familial Mediterranean fever (FMF), a genetically inherited disease
      characterized by fever and serositis, renal involvement is mainly AA amyloidosis.
      We report a patient with FMF who developed mesangial proliferative
      glomerulonephritis; presumably in response to colchicine treatment, the activity
      of the disease decreased and renal function tests and urinary findings
      normalized. This report emphasizes the concurrent existence of mesangial
      proliferative glomerulonephritis with FMF in the absence of renal amyloidosis.
      Due to increased inflammatory response observed in FMF, immunologic glomerular
      injury, a common cause of glomerulonephritis, may occur more frequently in
      patients with FMF.

PMID- 15971070
TI  - Membranous nephropathy associated with familial chronic ulcerative colitis in a
      12-year-old girl.
AB  - Glomerulonephritis is a rare complication in patients with inflammatory bowel
      disease. We report a case of membranous nephropathy (MN) in a 12.6-year-old girl
      with chronic ulcerative colitis. The girl was referred to the hospital with
      bloody diarrhea and arthralgia. Routine urinalysis showed 1 g/m(2) protein
      excretion in 24 h. Serum ANCA titers were positive. The diagnoses were confirmed
      by coloscopy and kidney biopsy. The patient's mother had also suffered from
      ulcerative colitis in adolescence. Proteinuria normalized under treatment with
      prednisone (60 mg/m(2)/day) and azathioprine, which was initiated to treat the
      colitis. Chronic ulcerative colitis can be associated with glomerulonephritis.

PMID- 15971071
TI  - The role of calcium antagonists in patients with chronic renal failure.
AB  - The objective of antihypertensive treatment in patients with chronic renal
      failure, many of whom have elevated blood pressure levels, is to reduce
      cardiovascular events and to slow down the progression of kidney function
      impairment. Calcium antagonists have been shown to be effective and safe
      antihypertensive drugs in patients from different age groups, including children.
      On the basis of numerous studies, one may conclude that the main benefit of
      antihypertensive therapy is because of the blood pressure lowering effect per se
      and that calcium antagonists do not differ from other antihypertensive drugs in
      the ability to prevent cardiovascular complications of hypertension. In
      particular, calcium antagonists are not inferior to other groups of
      antihypertensive agents in the prevention of coronary artery disease. There is,
      however, now evidence from controlled clinical trials that drugs interfering with
      the renin-angiotensin system are more beneficial than other antihypertensive
      agents in patients with chronic renal failure. Thus, several studies have
      demonstrated that ACE-inhibitors and, in patients with type-2 diabetic
      nephropathy, AT 1-antagonists are superior to other classes of antihypertensive
      drugs, including calcium antagonists, in delaying the progression of renal
      insufficiency. Therefore, in hypertensive patients with chronic renal failure
      antihypertensive treatment should be initiated with a drug that inhibits the
      renin-angiotensin system.

PMID- 15971072
TI  - Community-acquired enterococcal urinary tract infections.
AB  - Enterococcal urinary tract infection (UTI) is usually hospital-acquired and
      affects individuals with predisposing conditions. The aim of this study was to
      evaluate the community-acquired enterococcal UTIs in otherwise well children. We
      reviewed all the 257 first UTI episodes in children hospitalized in a General
      Hospital during a 5-year period. Enterococcus faecalis was isolated in 13
      episodes, accounting for 5.1% of the total UTIs. All strains were susceptible to
      ampicillin, vancomycin and nitrofurantoin. Imaging studies revealed major urinary
      tract abnormalities in 9 and parenchymal defects in 8 children. During a follow
      up period from 2 to 6 years, 4 children suffered break-through infections despite
      antibiotic prophylaxis, 3 developed renal scarring and 4 underwent corrective
      surgical procedures. Children with enterococcal UTIs presented with significantly
      higher rates of anatomical abnormalities and worse prognosis in terms of renal
      scarring, recurrences and corrective surgery compared with the total cohort of
      children with Gram-negative UTIs. However children with enterococcal UTIs did not
      present with a worse prognosis when compared with a group of children with Gram
      negative UTIs matched for age and degree of reflux. Enterococcal infection is not
      an independent risk factor for poor outcome, nevertheless positive urine culture
      including enterococci is highly indicative for underlying urinary tract
      abnormalities, recurrences, renal scarring, and need for surgical intervention.

PMID- 15971073
TI  - Sodium ferric gluconate complex therapy in anemic children on hemodialysis.
AB  - Pediatric patients with end-stage renal disease undergoing hemodialysis (HD)
      frequently develop anemia. Administration of recombinant human erythropoietin
      (rHuEPO) is effective in managing this anemia, although the additional demand for
      iron often results in iron deficiency. In adult patients undergoing HD,
      intravenous (IV) iron administration is known to replenish iron stores more
      effectively than oral iron administration. Nevertheless, IV iron supplementation
      is underutilized in pediatric patients, possibly because of unproved safety in
      this population. This international, multicenter study investigated the safety
      and efficacy of two dosing regimens (1.5 mg kg(-1) and 3.0 mg kg(-1)) of sodium
      ferric gluconate complex (SFGC) therapy, during eight consecutive HD sessions, in
      iron-deficient pediatric HD patients receiving concomitant rHuEPO therapy. Safety
      was evaluated in 66 patients and efficacy was evaluated in 56 patients.
      Significant increases from baseline were observed in both treatment groups 2 and
      4 weeks after cessation of SFGC dosing for mean hemoglobin, hematocrit,
      transferrin saturation, serum ferritin, and reticulocyte hemoglobin content.
      Efficacy and safety profiles were comparable for 1.5 mg kg(-1) and 3.0 mg kg(-1)
      SFGC with no unexpected adverse events with either dose. Administration of SFGC
      was safe and efficacious in the pediatric HD population. Given the equivalent
      efficacy of the two doses, an initial dosing regimen of 1.5 mg kg(-1) is
      recommended for pediatric HD patients.

PMID- 15971074
TI  - The mechanism of Mo-/Cu-dependent CO dehydrogenase.
AB  - Density functional theory computations at the B3LYP/SDDp//B3LYP/Lanl2DZ level
      were performed on model complexes derived from [(Me(2)C(2)S(2))Mo(O)(2)-S
      CuSMe](2-) or its oxo protonated form to gain insight into the reaction steps
      involved in substrate oxidation of a Mo-/Cu-dependent CO dehydrogenase. Only the
      bisoxo but not the hydroxo oxo complex was found to oxidize CO exothermically. A
      thiocarbamate complex structurally characterized as the reaction product of the
      enzyme with the inhibitor n-butylisonitrile corresponds to a thermodynamic well
      on the potential energy surface. For the formation of the analogous thiocarbonate
      complex from CO oxidation, however, we do not find a significant thermodynamic
      driving force. In the protein matrix of the enzyme this species should be further
      destabilized, as it requires the metal centers to move apart considerably from
      each other.

PMID- 15971075
TI  - Craniopharyngiomas: our experience in Lyon.
AB  - OBJECTIVE: We reviewed our experience in surgical treatment of
      craniopharyngiomas. Surgical treatment of craniopharyngiomas in children
      represents a challenge for neurosurgeons because it presents a different set of
      surgical problems. Results are controversial and debates concerning strategies to
      ameliorate the rate of success and to decrease the rate of morbidity and
      mortality are ongoing. Post-surgical quality of life is related to the anatomical
      relationship between the hypothalamic region, vascular structures and optic
      pathways. DISCUSSION: From 1985 to 2004, 60 children (age range, 4 months to 18
      years) were treated in our institution. Since 1987, all patients were studied
      with pre- and postoperative MRI. Two groups of patients were distinguished: a
      group of 36 patients treated with surgical direct surgery; a second group of 24
      patients treated only with intracystic chemotherapy with bleomycin (18 patients)
      or associated with surgery (six patients). In the first group, the removal of
      lesion was total in 74% of cases. Two patients died in the early postoperative
      period and two more died later (early mortality of 5% and late mortality of 11%).
      All patients presented ante-pituitary insufficiency and diabetes insipidus, which
      required substitutive treatment. Twenty-two patients presented with visual
      problems, including amaurosis in two cases. In the group treated with bleomycin,
      18 patients presented a primary cystic or a mixed form of craniopharyngioma and
      six patients showed a cystic recurrence. Eighteen patients were treated with
      bleomycin only. The dose used varied from 30 mg to a maximal dose of 150 mg, with
      a middle dose of 60 mg in the large majority of cases. In this group, the cyst
      disappeared in 12 patients and reduced to 30% of its initial volume, and
      stabilization of the lesion was achieved in the other six patients. Only 11
      patients presented partial endocrine insufficiency. Of the 18 patients, 16 were
      of school age, 14 of whom were following a normal educational program and two an
      assisted program. No mortality was reported. CONCLUSION: Our experience showed
      that in the group treated with intracystic chemotherapy alone, results were
      better with a low rate of morbidity and mortality. Endocrinological, visual and
      neuropsychological evaluations were also correlated with better outcome. In cases
      of cystic craniopharyngiomas, we considered bleomycin as the treatment of choice.
      For solid forms or for cases resistant to intracystic chemotherapy with
      bleomycin, direct surgery has to be proposed.

PMID- 15971076
TI  - [Computer-assisted arthrodesis of the sacroiliac joint].
AB  - Arthrodesis of the sacroiliac joint (SI) usually requires a large surgical
      exposure using the lateral approach. Computer-assisted surgery based on
      intraoperative 3D fluoroscopy imaging can reduce the approach to stab incisions.
      The clinical example shows the insertion of two screws and a cylindrical bone
      graft to achieve an arthrodesis of the SI joint. The intraoperatively navigated
      placement of implants and bone graft was performed only by stab incisions.

PMID- 15971077
TI  - Decreased intestinal glucose transport in the sgk3-knockout mouse.
AB  - Xenopus oocyte coexpression experiments revealed the capacity of the serum- and
      glucocorticoid-inducible kinase isoform 3 (SGK3) to up-regulate a variety of
      transport systems including the sodium-dependent glucose transporter SGLT1. The
      present study explored the functional significance of SGK3-dependent regulation
      of intestinal transport. To this end, experiments were performed in gene targeted
      mice lacking functional sgk3 (sgk3(-/-)) and their wild type littermates
      (sgk3(+/+)). Oral food intake and fecal dry weight were significantly larger in
      sgk3(-/-) than in sgk3(+/+) mice. Glucose-induced current (I(g)) in Ussing
      chamber as a measure of Na(+) coupled glucose transport was significantly smaller
      in sgk3(-/-) than in sgk3(+/+) mouse jejunal segments. Fasting plasma glucose
      concentrations were significantly lower in sgk3(-/-) than in sgk3(+/+) mice.
      Intestinal electrogenic transport of phenylalanine, cysteine, glutamine and
      proline were not significantly different between sgk3(-/-) and sgk3(+/+) mice. In
      conclusion, SGK3 is required for adequate intestinal Na(+) coupled glucose
      transport and impaired glucose absorption may contribute to delayed growth and
      decreased plasma glucose concentrations of SGK3 deficient mice. The hypoglycemia
      might lead to enhanced food intake to compensate for impaired intestinal
      absorption.

PMID- 15971078
TI  - Cellular and molecular function of mucolipins (TRPML) and polycystin 2 (TRPP2).
AB  - Mucolipins (transient receptor potential mucolipin, TRPML) and polycystin-2
      proteins (transient receptor potential polycystin, TRPP) constitute two small
      families of cation channels with motif and sequence similarities to the transient
      receptor potential (TRP) class of non-selective cation channels. Genetic defects
      in TRPML1 and TRPML3 in humans and in animal models cause the accumulation of
      large vacuoles, leading to a variety of cellular phenotypes including
      neurological and neurosensory deficiencies. TRPML1 is a Ca(2+)-, K(+)-, and Na(+)
      permeable cation channel sensitive to pH changes, and regulates a critical step
      in the maturation of late endosomes to lysosomes. Mutations of TRPP2 in humans
      result in autosomal dominant polycystic kidney disease. Molecular studies have
      demonstrated that TRPP2 and TRPP3 proteins function as Ca(2+)-regulated, non
      selective cation channels. During embryogenesis TRPP2 is active in node monocilia
      and plays a role in the establishment of left-right asymmetry. Recent results
      have indicated that TRPP2 interacts with polycystin-1 and that their interaction
      is important for their function as mechanosensitive channels at the primary
      cilium of renal epithelial cells. The interaction of polycystin family members
      appears to be conserved and is critical for fertilization and mating behavior. An
      emerging concept from the studies of the polycystin family is that they function
      as cation-influx based devices for sensing extracellular signals on ciliated
      structures. Here we review the function of TRPML1 and TRPP2 as representative
      members of these families, focusing on the genetics, physiology, and
      biochemistry.

PMID- 15971079
TI  - TRPC channels as signal transducers.
AB  - The study of the TRPC cation channels as signal transducers in sensory neurons is
      in its infancy. Mechanoreceptors that monitor arterial pressure are prime
      candidates for the involvement of TRPC channels as either primary mechanical
      transducers or as modulators of the transduction process. Their activity patterns
      can be regulated by growth factors such as BDNF and by a variety of ligands that
      activate Gq-coupled receptors, mechanisms that have been shown in heterologous
      expression systems to activate TRPC channels. We investigated the distribution of
      TRPC1 and TRPC3-7 in nodose sensory neurons and in their peripheral axons that
      terminate as mechanosensitive receptors in the aortic arch of the rat. Using
      immunocytochemical techniques we identified these six TRPC proteins in the soma
      of the nodose neurons but only TRPC1 and TRPC3-5 were found to distribute to the
      peripheral axons and the mechanosensory terminals. TRPC1 and TRPC3 extended into
      the low threshold complex sensory endings with very strong labeling. In contrast,
      TRPC4 and TRPC5 were found primarily in major branches of the receptor but
      immunoreactivity was weak in the region where mechanotransduction is presumed to
      occur. Terminals arising from unmyelinated fibers also expressed TRPC1 and TRPC3
      5 but not all fibers expressed all of the channels suggesting that specific TRPC
      protein may be aligned with previously described subclasses of the unmyelinated C
      fibers.

PMID- 15971080
TI  - Homo- and heteromeric assembly of TRP channel subunits.
AB  - Mammalian homologues of the Drosophila melanogaster transient receptor potential
      (TRP) channels are the second largest cation channel family within the
      superfamily of hexahelical cation channels. Most mammalian TRP channels function
      as homooligomers and mediate mono- or divalent cation entry upon activation by a
      variety of stimuli. Because native TRP channels may be multimeric proteins of
      possibly complex composition, it is difficult to compare cation conductances in
      native tissues to those of clearly defined homomeric TRP channel complexes in
      living cells. Therefore, the possibility of heteromeric TRP channel assembly has
      been investigated in recent years by several groups. As a major conclusion of
      these studies, most heteromeric TRP channel complexes appear to consist of
      subunit combinations only within relatively narrow confines of phylogenetic
      subfamilies. Although the general capability of heteromer formation between
      closely related TRP channel subunits is now clearly established, we are only
      beginning to understand whether these heteromeric complexes are of physiological
      significance. This review summarizes the current knowledge on the promiscuity and
      specificity of the assembly of channel complexes composed of TRPC-, TRPV- and
      TRPM-subunits of mammalian TRP channels.

PMID- 15971081
TI  - The diacylgylcerol-sensitive TRPC3/6/7 subfamily of cation channels: functional
      characterization and physiological relevance.
AB  - Among the "classical" or "canonical" transient receptor potential (TRPC) family,
      the TRPC3, -6, and -7 channels share 75% amino acid identity and are gated by
      exposure to diacylglycerol. TRPC3, TRPC6, and TRPC7 interact physically and
      coassemble to form functional tetrameric channels. This review focuses on the
      TRPC3/6/7 subfamily and describes their functional properties and regulation as
      homomers obtained from overexpression studies in cell lines. It also summarizes
      their heteromultimerization potential in vitro and in vivo and presents initial
      data concerning their physiological functions analyzed in isolated tissues with
      downregulated channel activity and gene-deficient mouse models.

PMID- 15971082
TI  - Structure and function of TRPV1.
AB  - Capsaicin, the main ingredient in hot chili peppers, elicits a sensation of
      burning pain by selectively activating sensory neurons that convey information
      about noxious stimuli to the central nervous system. The capsaicin receptor,
      transient receptor potential vanilloid 1 (TRPV1), is predicted to have six
      transmembrane (TM) domains and a short, pore-forming hydrophobic stretch between
      the fifth and sixth TM domains, and is activated not only by capsaicin but also
      by heat (>43 degrees C), acid and various lipids. Within the TPRV1 protein, many
      regions and amino acids involved in specific functions (multimerization,
      capsaicin action, proton action, heat activation, desensitization, permeability,
      phosphorylation and modulation by lipids) have been identified since the cloning
      in 1997. Given the fact that TRPV1 is a key molecule in peripheral nociception,
      these regions and amino acids could prove useful for the development of novel
      anti-nociceptive or anti-inflammatory agents.

PMID- 15971083
TI  - Neurobiology of TRPC2: from gene to behavior.
AB  - The mammalian vomeronasal organ (VNO), a part of the accessory olfactory system,
      plays an essential role in the sensing of pheromonal signals. The VNO has emerged
      as an excellent model to investigate the functional role of transient receptor
      potential (TRP) channels in intact neurons and intact physiological systems.
      TRPC2, a member of the (canonical) TRPC subfamily, is highly localized to the
      dendritic tip of vomeronasal sensory neurons. Phenotypic analysis of mice
      exhibiting a targeted deletion in the TRPC2 gene has established that TRPC2
      occupies a fundamental role in the transduction machinery underlying the
      detection of pheromone signals by the VNO. TRPC2-deficient mice exhibit striking
      behavioral defects in the regulation of sexual and social behaviors. A previously
      unknown Ca(2+)-permeable, diacylglycerol (DAG)-activated cation channel found at
      the dendritic tip of vomeronasal neurons is severely defective in TRPC2 mutants,
      providing the first clear example for the existence of native DAG-gated cation
      channels in the mammalian nervous system. The experimental strategy employed in
      the mouse VNO now serves as a powerful model for examining the native functions
      of other TRP genes.

PMID- 15971084
TI  - Vasopressin release during endotoxaemic shock in mice lacking inducible nitric
      oxide synthase.
AB  - We tested the hypothesis that nitric oxide (NO) arising from the action of
      inducible nitric oxide synthase (iNOS) is responsible for the deficiency in
      vasopressin (AVP) release and consequent hypotension during endotoxaemic shock.
      Wild-type (WT) and iNOS knockout mice (iNOS(-/-)) were given either saline or
      Escherichia coli lipopolysaccharide (LPS, 1.0 mg/kg i.v., final volume 0.03 ml).
      Mean arterial blood pressure (MAP) was measured and plasma AVP levels determined
      before and after LPS or saline injection. In WT mice, MAP was significantly lower
      2 h after LPS administration and remained low for the remainder of the 6-h
      observation period. AVP plasma levels were increased at the 2nd and 4th h of the
      experiment, returning thereafter to basal levels. Conversely, LPS injection in
      iNOS iNOS(-/-) mice elicited a sustained increase in plasma AVP concentration and
      attenuated the fall in blood pressure. These data indicate that NO arising from
      the iNOS plays an important inhibitory role in AVP release during endotoxaemia
      and may be responsible for the hypotension occurring during this vasodilatory
      shock.

PMID- 15971085
TI  - Tree allometry and improved estimation of carbon stocks and balance in tropical
      forests.
AB  - Tropical forests hold large stores of carbon, yet uncertainty remains regarding
      their quantitative contribution to the global carbon cycle. One approach to
      quantifying carbon biomass stores consists in inferring changes from long-term
      forest inventory plots. Regression models are used to convert inventory data into
      an estimate of aboveground biomass (AGB). We provide a critical reassessment of
      the quality and the robustness of these models across tropical forest types,
      using a large dataset of 2,410 trees >or= 5 cm diameter, directly harvested in 27
      study sites across the tropics. Proportional relationships between aboveground
      biomass and the product of wood density, trunk cross-sectional area, and total
      height are constructed. We also develop a regression model involving wood density
      and stem diameter only. Our models were tested for secondary and old-growth
      forests, for dry, moist and wet forests, for lowland and montane forests, and for
      mangrove forests. The most important predictors of AGB of a tree were, in
      decreasing order of importance, its trunk diameter, wood specific gravity, total
      height, and forest type (dry, moist, or wet). Overestimates prevailed, giving a
      bias of 0.5-6.5% when errors were averaged across all stands. Our regression
      models can be used reliably to predict aboveground tree biomass across a broad
      range of tropical forests. Because they are based on an unprecedented dataset,
      these models should improve the quality of tropical biomass estimates, and bring
      consensus about the contribution of the tropical forest biome and tropical
      deforestation to the global carbon cycle.

PMID- 15971086
TI  - How painful are shockwave lithotripsy and endoscopic procedures performed at
      outpatient urology clinics?
AB  - Our aim was to investigate the subjective pain felt by patients during shockwave
      lithotripsy (SWL) and endoscopic procedures such as cystoscopy, retrograde
      ureteral stenting, retrograde pyelography (RGP), and ureteroscopic lithotripsy
      performed in an outpatient clinic, and to identify how severe pain during such
      procedures is. We estimated subjective pain in 984 patients after SWL (186),
      cystoscopy (489), retrograde ureteral stenting (127), RGP (97), and ureteroscopic
      lithotripsy (85) performed by a single expert in an outpatient clinic using a
      prospective questionnaire with a ten point visual analog scale between January
      2001 and December 2003. There was no premedication in any procedure except
      ureteroscopic lithotripsy for which an intramuscular injection of analgesics
      (pethidine HCl 50 mg) was used. The pain scale score in SWL was 6.62+/-2.27, the
      highest among the procedures (P<0.05). Pain scores for endoscopies were 4.48+/
      2.07 in retrograde ureteral stenting, 3.81+/-2.06 in ureteroscopic lithotripsy,
      3.72+/-1.75 in RGP, and 3.08+/-1.95 in cystoscopy. In this study, we observed
      that patients feel most pain in SWL without anesthesia, and that pain during
      ureteroscopic lithotripsy under local anesthesia is not high, compared with other
      endoscopic procedures.

PMID- 15971087
TI  - Effectiveness of electro-acupuncture compared to sedo-analgesics in relieving
      pain during shockwave lithotripsy.
AB  - The aim of this study was to compare the clinical efficacy of electro-acupuncture
      (EA) with the combination of tramadol+midazolam (TM) for pain relief during
      outpatient extracorporeal shockwave lithotripsy (ESWL). A total of 35 patients
      (20 men, 15 women) with stones located in the pelvicalyceal system of the kidney
      were randomized prospectively to undergo lithotripsy with a third generation
      lithotriptor (Stone Lith, smart PCK) after receiving either EA (n=17) or TM
      (n=18) for sedation and analgesia. EA treatment was applied to patients by the
      same licensed acupuncturist 30 min prior to ESWL in group EA. Tramadol (1.5
      mg/kg) 30 min before the start of lithotripsy and midazolam (0.06 mg/kg) 5 min
      prior to ESWL were given as a sedo-analgesic intravenously to group TM. During
      ESWL, blood pressure, heart rate, pain and sedation levels were measured at
      baseline and every 15 min thereafter. The pain intensity perceived during
      lithotripsy was evaluated using a visual analog scale (VAS). There was no
      statistical differences in the diameters of the stones and age of the patients
      between groups (P=0.590; P=0.568, respectively). In the EA group, the median of
      maximum energy level achieved was 16.0 kV (range 10-23 kV), while it was 18.0 kV
      (range 10-20 kV) in the TM group. There was no statistically significant
      difference between the maximum energy levels applied to the patients during ESWL
      (P=0.613). The median numbers of shockwaves were 2,114 (range 1,100-3,800) and
      2,200 (range 1,500-3,200) in the EA and TM groups, respectively. In the TM group,
      the numbers of shockwaves used were higher than in group EA during ESWL. However,
      this difference was not significant (P=0.732). VAS scores were consistently lower
      in the EA group compared with the TM group throughout the ESWL procedure. The
      median VAS score was 5.0 (range 1-10) in the EA group while it was 8.0 (range 2
      10) in the TM group. The patients who underwent EA had lower median scores of VAS
      than patients who took only conservative treatment, but this difference was not
      significant (P=0.245). When both groups were compared for stone-free rates, no
      significant difference was found [82.3% (14/17) for group EA, 88.8% (16/18) for
      group TM] (P=0.658). Durations of ESWL procedures were similar in both groups
      [median 27.4 min (range 15.7-34.3) in group EA vs 27.1 min (range 16.1-33.6) in
      group TM] (P=0.517). No side effects was seen in any patient who received EA.
      Side effects such as mild orthostatic hypotension and dizziness occurred in
      patients given sedo-analgesia, but these were not severe enough to require any
      patient to be excluded from the study. Our study shows that EA is an effective
      method for inducing sedation with analgesia without any demonstrable side
      effects.

PMID- 15971088
TI  - [Health economics studies in dermatology].
AB  - Because of reduced resources for health care, provision of modern effective
      dermatologic care for patients with German public health insurances has become
      more and more difficult. This survey is designed to aid in the assessment of
      published health economic studies as well as encourage participation in health
      economic evaluations. These studies should analyze and optimize the allocation of
      the available resources. Four main approaches can be used to calculate the
      incidental expenses; they differ in their methods of evaluation and assessment of
      health services. They all offer methods to calculate the anticipated costs and
      consequences. The methods include cost minimization analysis (CMA), cost
      effectiveness analysis (CEA), cost utility analysis (CUA) or cost benefit
      analysis (CBA). Many subgroups also exist. Important criteria for the evaluation
      of health economic trials and hints for the publication of the results are
      provided on the basis of the recommendations for health economic evaluations.

PMID- 15971090
TI  - Vanillate metabolism in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum, a Gram-positive soil bacterium belonging to the
      mycolic acids-containing actinomycetes, is able to use the lignin degradation
      products ferulate, vanillate, and protocatechuate as sole carbon sources. The
      gene cluster responsible for vanillate catabolism was identified and
      characterized. The vanAB genes encoding vanillate demethylase are organized in an
      operon together with the vanK gene, coding for a transport system most likely
      responsible for protocatechuate uptake. While gene disruption mutagenesis
      revealed that vanillate demethylase is indispensable for ferulate and vanillate
      utilization, a vanK mutation does not lead to a complete growth arrest but to a
      decreased growth rate on protocatechuate, indicating that one or more additional
      protocatechuate transporter(s) are present in C. glutamicum.

PMID- 15971089
TI  - Inhibitory effects of mediterranean sponge extracts and metabolites on larval
      settlement of the barnacle Balanus amphitrite.
AB  - One of the most promising alternative technologies to antifouling paints based on
      heavy metals is the development of coatings whose active ingredients are
      compounds naturally occurring in marine organisms. This approach is based on the
      problem of epibiosis faced by all marine organisms and the fact that a great
      number of them cope with it successfully. The present study investigated the
      antifouling activity of a series of extracts and secondary metabolites from the
      epibiont-free Mediterranean sponges Ircinia oros, I. spinosula, Cacospongia
      scalaris, Dysidea sp., and Hippospongia communis. Antifouling efficacy was
      evaluated by the settlement inhibition of laboratory-reared Balanus amphitrite
      Darwin cyprids. The most promising activity was exhibited by the metabolites 2
      [24-acetoxy]-octaprenyl-1-4-hydroquinone (8a), dihydrofurospongin II (10), and
      the alcoholic extract of Dysidea sp.

PMID- 15971091
TI  - Effect of different carbon sources on endochitinase production by Colletotrichum
      gloeosporioides.
AB  - The present work analyzes the production of endochitinase by Colletotrichum
      gloeosporioides, a phytopathogenic fungus, using six different carbon sources and
      two pH values. For quantitative assay of endochitinase activity in solution, the
      synthetic substrate 4-methylumbelliferyl-beta-D-N,N',N"-triacetylchitotrioside
      was used. The major productions were obtained at pH 7.0 and 9.0, when colloidal
      chitin and glucose were used, whereas xylose and lactose were not good carbon
      sources. When testing different concentrations of colloidal chitin, glucose and
      glucosamine, colloidal chitin 0.5% was the best substrate, giving values of 2.4 U
      at the fifth day. When using glucose, best production occurred at 0.3%
      concentration, after 5 days growth, with values of 1.31 U. Endochitinase
      production was markedly decreased in high levels of glucose and in all
      glucosamine concentrations tested. SDS-PAGE co-polymerized with glycol-chitin
      analysis showed three major activity bands of 200, 100, and 95 kDa, when
      incubated at 50 degrees C.

PMID- 15971093
TI  - Molecular cloning of a phytase gene (phy M) from Pseudomonas syringae MOK1.
AB  - A phytase gene (phy M) was cloned from Pseudomonas syringae MOK1 by two steps of
      degenerate PCR and inverse PCR. This gene consists of 1,287 nucleotides and
      encodes a polypeptide of 428 amino acids with a deduced molecular mass of 46,652
      kDa. Based on its amino acid sequence, the Phy M shares the active site RHGXRXP
      and HD sequence motifs, typically characterized by histidine acid phosphatases
      familly. Each phy M gene fragment encoding mature Phy M with its own signal
      sequence (pEPSS) and without (pEPSM) was subcloned into the E. coli BL21 (DE3)
      expression vector, pET22b (+). The enzyme activity in crude extracts of clone
      pEPSM was 2.514 Umg(-1) of protein, and about 10-fold higher than that of clone
      pEPSS.

PMID- 15971092
TI  - Identification of a lactose-responsive element upstream of the promoter of
      Bacillus megaterium beta-galactosidase-encoding gene mbgA.
AB  - The Bacillus megaterium mbgA gene encodes a lactose-hydrolyzing beta
      galactosidase. An AraC/XylS-type activator BgaR can activate mbgA transcription
      in response to lactose. In this report, we show by various deletion analyses and
      point mutagenesis analyses that an inverted repeat centered at position -60.5
      relative to the mbgA transcriptional initiation site is the cis-acting element
      responsible for lactose induction of mbgA expression.

PMID- 15971094
TI  - Purification and characterization of Warnericin RB4, anti-Alicyclobacillus
      bacteriocin, produced by Staphylococcus warneri RB4.
AB  - In this study we characterized a bacteriocin, warnericin RB4, produced by
      Staphylococcus warneri RB4. Warnericin RB4 activity was completely inactivated by
      trypsin and actinase E. The activity was stable at 100 degrees C for 15 min, and
      had a pH range of 2 to 6. S. warneri RB4 showed antibacterial activity against
      only Alicyclobacillus acidoterrestris, A. acidocaldarius, and Micrococcus luteus,
      among 34 bacterial species tested. The amino acid sequence of the purified
      bacteriocin contained 27 amino acid residues (K-K-K-S-G-V-I-P-X-V-X-H-D-X-H-M-N-X
      F-Q-F-V-F-X-X-X-S). The molecular mass of the bacteriocin was estimated to be
      2,958.2 Da by ESI-MS. These results show that the Warnericin RB4 exhibiting
      specific antibacterial activity against thermo-acidophiles, Alicyclobacillus
      spp., is a Nukacin ISK-1 or closely related bacteriocin, classified with class IA
      (Lacticin 481 types). This is the first report that Warnericin RB-4 is effective
      to inhibit the growth of causative microorganisms of spoilage in various acidic
      drinks. Warnericin RB4 might prove useful in fruit juices and fruit juice
      containing drinks.

PMID- 15971095
TI  - Development of a highly sensitive method for detection of clarithromycin
      resistant Helicobacter pylori from human feces.
AB  - Gastric infection of clarithromycin (CAM)-resistant Helicobacter pylori is one of
      the major causes of failure to eradicate this organism. A noninvasive and useful
      method for the detection of CAM-resistant H. pylori from human feces by
      restriction fragment length polymorphism (RFLP)-nested polymerase chain reaction
      (PCR) targeting the mutation of the 23S rRNA gene that confers CAM-resistance in
      H. pylori was developed in this study. Our nested PCR method detected DNA of H.
      pylori in feces with high sensitivity and specificity compared with both an
      enzyme-linked immunoadsorbent assay (ELISA) of H. pylori in feces and the
      isolation of H. pylori from gastric biopsy. Furthermore, the results of mutation
      analysis of the H. pylori 23S rRNA gene amplified from feces completely
      correlated with both that of the H. pylori 23S rRNA gene amplified from the
      isolates of gastric biopsy and the susceptibility of H. pylori isolates to CAM.
      Therefore, our results show that this RFLP/nested PCR method is useful for the
      accurate diagnosis of CAM-resistant H. pylori infection from feces.

PMID- 15971096
TI  - Putrescine accumulation in wine: role of Oenococcus oeni.
AB  - Putrescine, the most abundant biogenic amine in wine, was proved to be produced
      by Oenococcus oeni strains in wine not only from ornithine but also from
      arginine. In this case, putrescine may originate from strains possessing the
      complete enzyme system to convert arginine to putrescine or by a metabiotic
      association, with an exchange of ornithine, between strains capable of
      metabolizing arginine to ornithine but unable to produce putrescine and strains
      capable of producing putrescine from ornithine but unable to degrade arginine.
      Putrescine production by this metabiotic association occurred once the malolactic
      fermentation was completed, whereas conversion of ornithine to putrescine by a
      single culture of the ornithine decarboxylating strain concurred with the
      degradation of malic acid. Moreover, in the former case, putrescine formation
      proceeded more slowly than in the latter. Metabiosis may play an important role
      in the accumulation of putrescine in wine, arginine being one of the major amino
      acids found in wine.

PMID- 15971097
TI  - Stenting of obstructing colonic cancer: a real advance or an irrelevance to the
      laparoscopic surgeon?

PMID- 15971098
TI  - Laparoscopic transabdominal preperitoneal approach to place a polypropylene mesh
      on the abdominal wall: an experimental swine model of a technique that can be
      used for incisional hernia repair.
AB  - BACKGROUND: The placement of intraabdominal polypropylene mesh entails risks of
      adhesions and fistulas that can be avoided by preperitoneal placement. METHODS:
      This comparative, open, experimental, prospective, randomized, and transversal
      study randomized pigs into two groups of 11 each for intraperitoneal (IPOM) or
      preperitoneal (TAPP) polypropylene mesh placement by laparoscopy. Diagnostic
      laparoscopy and tissue en-bloc resection was performed 28 days postoperatively
      for histopathologic analysis. RESULTS: The following data were observed for the
      two study groups: surgical time (IPOM: 35.73 +/- 4.22 min; TAPP: 58.09 +/- 6.28
      min; p = or < 0.0001); adhesions (IPOM: 81.81%; TAPP: 27.27%; p = 0.032), grade
      III for IPOM and grade II for TAPP (p = 0.001); and interloop adhesions (IPOM:
      81.81%; TAPP: 9.09%; p = 0.003). No fistulas were found in either group. The TAPP
      procedure showed better integration of mesh, without lesion to abdominal organs.
      Two complications, occurred with IPOM, and one with TAPP (p = 1.0, not
      significant). CONCLUSIONS: The perperitoneal technique requires more time, but
      has fewer adhesions and less intraabdominal inflammatory response. It is a
      feasible technique that may diminish risks in the laparoscopic treatment of
      incisional hernias with polypropylene mesh.

PMID- 15971099
TI  - Clinical and histological correlations in prolactinomas, with special reference
      to bromocriptine resistance.
AB  - BACKGROUND: Prolactinomas usually exhibit a benign course and can be safely and
      effectively managed by dopamine agonists (DA). However, some are locally invasive
      and may show resistance to DA therapy, and the management of such cases remains
      controversial. The aim of the present study was to determine whether histological
      features and markers of cell proliferation correlated to the clinical behaviour
      of prolactinomas and with DA resistance. METHOD: This retrospective study
      included 74 cases (36 men and 38 women) who had monohormonal prolactinomas
      removed by transsphenoidal surgery. The prolactinomas were categorized on the
      basis of tumour size (48 macroadenomas), invasion of the cavernous sinus (n =
      31), and resistance to bromocriptine (BRC) therapy (n = 14). Group 1 consisted of
      non-invasive microprolactinomas (n = 24), group 2 of non-invasive
      macroprolactinomas (n = 19), group 3 of invasive non-BRC-resistant tumours (n =
      19), and group 4 of invasive BRC-resistant tumours (n = 12). The later group
      included one case of carcinoma with bone and lung metastases. Seven additional
      parameters were studied, these being age, sex, basal prolactin (PRL) levels, the
      Ki-67 and PCNA labelling indices (LI), mitotic count, and cellular atypia.
      FINDINGS: Age and preoperative PRL levels did not correlate to the histological
      parameters studied. Tumour size and invasion were related to cellular atypia and
      the Ki-67 LI. BRC-resistant tumours were more frequently invasive (12/14) than
      BRC-responsive tumours (11/30; p = 0.002) and were more frequent in men than in
      women (33 versus 5%; p = 0.003). BRC-resistant tumours had a higher Ki-67 LI and
      mitotic count (4.2+/-2.0% and 4+/-1, respectively) than other tumours (0.7+/-0.2%
      and 1+/-0, respectively; p<0.05). The strongest correlations with tumoural
      staging were seen with male sex and high mitotic activity. Six out of the 12
      invasive BRC-resistant macroprolactinomas, including the PRL secreting carcinoma,
      exhibited histological features of aggressiveness (a mitotic count >/=3 [i.e. in
      the fourth quartile] and/or a high Ki-67 LI and cellular atypia). CONCLUSIONS: In
      this surgical retrospective series, histological signs of aggressiveness are
      present in 50% of invasive and BRC-resistant prolactinomas, which are more
      frequent in men than in women. This fits with the behaviour of BRC-resistant
      prolactinomas, which can continue to grow despite DA treatment. These findings
      justify the long-term follow up of these tumours, and the use of surgery and/or
      radiotherapy if there is concern about the control of tumour growth.

PMID- 15971100
TI  - Is idiopathic normal pressure hydrocephalus an independent entity?

PMID- 15971103
TI  - Innate and acquired plasticity of the intestinal immune system.

PMID- 15971104
TI  - Ontogeny of intestinal epithelium immune functions: developmental and
      environmental regulation.
AB  - Intestinal mucosa integrates primary digestive functions with immune functions
      such as pathogen surveillance, antigen transport and induction of mucosal
      immunity and tolerance. Intestinal adaptive immunity is elicited in organized
      mucosa-associated lymphoid tissue (O-MALT) that is composed of antigen-presenting
      cells and lymphocytes and achieved by effector cells widely distributed in mucosa
      (diffuse MALT or D-MALT). Interaction between the intestinal epithelium, the O
      MALT and the diffuse MALT plays a critical role in establishing an adequate
      immune response. In regions associated to O-MALT, lympho-epithelial cross-talks
      lead to acquisition of a specific epithelial phenotype that contributes to O-MALT
      organization and functionality. Beyond the expression of several innate immune
      functions, the intestinal epithelium may directly take up and present antigens
      due to the expression of major histocompatibility complex (MHC) and MHC-related
      molecules. A complex genetic program that will be outlined in the present review
      controls the development of immune functions of the intestinal epithelium. The
      effect of environmental signals on the modulation of this ontogenetic program
      during development and neonatal life, from bioactive components of amniotic fluid
      to lactation and bacterial colonization, will be discussed.

PMID- 15971105
TI  - Innate defenses of the intestinal epithelial barrier.
AB  - The innate immune system plays a crucial role in maintaining the integrity of the
      intestine and protecting the host against a vast number of potential microbial
      pathogens from resident and transient gut microflora. Mucosal epithelial cells
      and Paneth cells produce a variety of antimicrobial peptides (defensins,
      cathelicidins, crytdinrelated sequence peptides,
      bactericidal/permeabilityincreasing protein, chemokine CCL20) and bacteriolytic
      enzymes (lysozyme, group IIA phospholipase A2) that protect mucosal surfaces and
      crypts containing intestinal stem cells against invading microbes. Many of the
      intestinal antimicrobial molecules have additional roles of attracting
      leukocytes, alarming the adaptive immune system or neutralizing proinflammatory
      bacterial molecules. Dysfunction of components of the innate immune system has
      recently been implicated in chronic inflammatory bowel diseases such as Crohn's
      disease and ulcerative colitis, illustrating the pivotal role of innate immunity
      in maintaining the delicate balance between immune tolerance and immune response
      in the gut.

PMID- 15971106
TI  - A marvel of mucosal T cells and secretory antibodies for the creation of first
      lines of defense.
AB  - The mucosal immune system acts as a first line of defense against bacterial and
      viral infections while also playing a crucial role in the establishment and
      maintenance of mucosal homeostasis between the host and the outside environment.
      In addition to epithelial cells and antigen-presenting cells (dendritic cells and
      macrophages), B and T lymphocytes form a dynamic mucosal network for the
      induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte
      (CTL) responses. This review seeks to shed light on the pathways of induction and
      regulation of these responses and to elucidate the role they simultaneously play
      in fending off pathogen invasion and maintaining mucosal homeostasis.

PMID- 15971107
TI  - Oral tolerance and regulation of mucosal immunity.
AB  - Regulated mechanisms sustain the ability of the gut immune system to discriminate
      harmless food antigens (Ag) and commensal bacteria from pathogenic
      microorganisms, resulting in tolerance versus protective immunity, respectively.
      Antigens of the gut commensals are not simply ignored, but rather trigger an
      active immunosuppressive process, more commonly known as oral tolerance, which
      prevents the outcome of immunopathology. Both intrinsic properties of the gut
      microenvironment and cellular actors, as well as peripheral events induced by
      systemic dissemination of oral Ag, promote the induction of regulatory mechanisms
      that ensure maintenance of gut homeostasis. The aim of this review is to provide
      a synthetic update on the mechanisms of oral tolerance, with particular emphasis
      on the complex interplay between regulatory CD4+ T cells, dendritic cells and the
      gut microenvironment.

PMID- 15971108
TI  - Peyer's patch dendritic cells as regulators of mucosal adaptive immunity.
AB  - The mucosal immune system maintains a delicate balance between providing robust
      defense against infectious pathogens and, at the same time, regulating responses
      toward innocuous environmental and food antigens and commensal microbes. The
      Peyer's patch (PP) has been studied in detail as a major inductive site for
      mucosal immunity within the small intestine. While the mechanisms responsible for
      the induction of mucosal immunity versus tolerance are not yet fully understood,
      recent studies have highlighted mucosal dendritic cells (DCs) as regulators of
      the immune responses to orally administered antigens. Here we discuss recent
      studies that describe the role of PP DCs in immune induction and speculate on the
      mechanism by which the resident DCs regulate T cell and immunoglobulin A (IgA)
      responses in the gastrointestinal mucosa.

PMID- 15971109
TI  - Innate immune relationship between commensal flora and the mammalian intestinal
      epithelium.
AB  - Commensal bacteria in the lumen of the intestine exist in a mutually advantageous
      relationship with the mammalian host, providing benefits such as increased
      metabolic/digestive capabilities and exclusion of harmful microbes, and in turn
      receiving a nutrient-rich environment. However, in the context of a dysfunctional
      intestinal epithelial barrier, commensal bacteria may elicit an immune
      inflammatory response similar to what occurs during infection by a pathogen.
      Recent work has established that most eukaryotic cells possess families of
      receptors that can detect the structural signatures of prokaryotic life. Cells
      may respond to the perception of microbes by activating distinct cytoplasmic
      signaling cascades that ultimately result in the transcriptional activation of
      genes needed for proinflammatory and anti-apoptotic functions, as well as for a
      pro-apoptotic response. Collectively, these responses generally suffice to
      eliminate microbial threats and may be integral to normal intestinal homeostasis.
      An understanding of these mechanisms, as well as those by which microbes
      themselves influence intestinal epithelial responses, may help provide a new
      perspective on the pathogenesis of intestinal diseases.

PMID- 15971110
TI  - Contribution of microbial-associated molecules in innate mucosal responses.
AB  - Both innate immunity and mucosal surfaces provide the first line of defence
      against mucosal infections. Innate immunity is a universal and evolutionarily
      conserved form of host defence that senses microbial organisms. Recent advances
      in the field of immunology are due mainly to the discovery of the role of Toll
      like receptors (TLRs), which recognize conserved microbial molecules. TLR
      stimulation induces specific patterns of gene expression that lead to the shaping
      of innate and adaptive immunity. Since mucosal tissues are colonized by innocuous
      microflora and challenged by infectious pathogens, activation of TLRs in
      epithelial and lamina propria cells must be tightly controlled to avoid
      inappropriate signalling that might lead to mucosal inflammation. This review
      aims to highlight novel insight on the molecules, pathways and gene expression
      networks associated with microbial recognition by TLRs and mucosal immunity.

PMID- 15971111
TI  - Cyclin H is targeted to the nucleus by C-terminal nuclear localization sequences.
AB  - Cdk-activating kinase (CAK) is a trimeric complex consisting of cdk7, cyclin H,
      and MAT1, which activates the cell-cycle-regulating cdks through T loop
      phosphorylation. In addition, other substrates of the CAK complex have been
      identified when CAK is assembled with the TFIIH core proteins, thereby regulating
      transcription and nucleotide excision repair. Little is known about the
      regulation of the CAK complex through cyclin H. In this study we further analyzed
      cyclin H regulation and identified two basic clusters in the C terminus of the
      protein as putative nuclear localization sequences (NLSs). Fusion constructs of
      full-length and truncated cyclin H sequences demonstrated the functionality of
      the NLSs. A peptide-binding assay revealed that at least one NLS interacts with
      the nuclear import receptors importin alpha/beta. Phosphorylation in the vicinity
      of the NLSs by cyclin C/cdk8 or protein kinase CK2, however, does not influence
      the nuclear translocation of cyclin H.

PMID- 15971112
TI  - Antigen specific immunotherapy: Quo vadis?

PMID- 15971113
TI  - Antigen specific active immunotherapy: lessons from the first decade.
AB  - Malignant melanoma is a tumour with a steeply rising incidence and scarce
      therapeutic options once metastatic. Approximately 1200 new cases are reported
      yearly in Switzerland with roughly 220 deaths/year. An important particularity of
      melanoma is its immunogenicity, which has long been recognized and investigated
      using various clinical immunization protocols in the last fifty years. The year
      1991, when the first melanoma associated antigen was molecularly characterized,
      represents a turning point in the quest for a melanoma immunotherapy. This opened
      the era of antigen specific active immunotherapy. Many clinical centres have
      developed immunization strategies in an adjuvant setting for the treatment of
      metastatic melanoma. The molecular characterization of melanoma associated
      antigens allows a fine monitoring of the elicited immune response. Certain
      clinical responses to these efforts have been seen and a phase of reflection is
      now ongoing, with refinements and further sophistication taking place in order to
      fully realize the potential of antigen specific active immunotherapy. Here we
      provide an overview of the technologies used and of the progress reported in
      melanoma immunotherapy since 1991. Furthermore, we propose some research lines in
      basic and translational research aimed at improving our capacity to induce
      specific and clinically relevant immune responses against melanoma.

PMID- 15971114
TI  - Education and a standardized management protocol improve the assessment and
      management of asthma in the emergency department.
AB  - STUDY OBJECTIVE: To evaluate the effect of a standardized management protocol on
      acute asthma care in the emergency department (ED). METHOD: We conducted a before
      after study regarding acute asthma management. Deficiencies in acute asthma care
      over a time period of 19 month (January 1997- October 1998) were identified.
      Subsequently a management protocol consisting of an assessment sheet and written
      guidelines for the initial management of acute asthma in the emergency
      department, was developed. In addition, physicians and nurses of the emergency
      department were informed about the recommendations given in the guidelines, and
      instructed in peak-flow meter use. The assessment sheet was introduced in January
      2002 and posted at several locations in the emergency department. Between
      February 2002 and August 2003 the acute asthma consultations in the emergency
      department were consecutively registered. Data on medical history, physical
      examination and objective measurements of airflow obstruction, as well as data on
      treatment and assessment of the response to therapy were collected. In addition,
      medication and instructions at discharge were reviewed and compared with the
      results before the introduction of the assessment sheet. RESULTS: The first group
      consisted of patients seen between January 1997 and October 1998; the second
      group consisted of all patients seen between February 2002 and August 2003 (104
      vs 273 patients respectively). Both groups had a similar gender distribution (56%
      females in the first group vs 53% females in the second group) and the mean age
      of both groups was also alike (median 33 vs 36 years). Most patients had a known
      history of asthma (76% in the first group vs 70% in the second group). The self
      referral rate was high in both groups (86% vs 96% respectively). Blood pressure
      and pulse rate were reported in the majority of patients (95% vs 98%
      respectively), whereas the respiratory rates were reported in 14% of patients in
      the first group vs 65% of patients in the second group. The introduction of the
      assessment sheet led to an increased measurement of initial airflow obstruction
      (53% of patients in the first group vs 96% of patients in the second group) as
      well as repeated measures under treatment (36% of patients in the first group vs
      85% of patients in the second group). Repeated inhalations with short-acting
      inhaled beta-agonists, and use of systemic corticosteroid therapy at admission
      and at discharge increased significantly (from 31% to 84%, 43% to 68% and 37% to
      70% respectively). CONCLUSION: The assessment and management of patients
      presenting to the emergency department with acute asthma can be improved with a
      guideline based management protocol, and by educating physicians and nurses in
      the management of acute asthma.

PMID- 15971115
TI  - Explicit versus implicit risk assessment for the indication of antithrombotic
      prophylaxis in acutely ill medical in-patients.
AB  - QUESTIONS UNDER STUDY: The indication of venous thromboembolism (VTE) prophylaxis
      in acutely ill patients admitted to medical departments is not well-defined.
      Consensus groups have published recommendations and guidelines, addressing this
      issue. We investigated whether a guideline (explicit risk assessment) would
      improve the formerly used implicit risk assessment. METHODS: We compared two
      groups of patients consecutively admitted to our department during a 4-months
      period each. Group 1 was assessed prospectively and treated according to a
      guideline (explicit assessment). Group 2 consisted of the patients hospitalised
      in the four months prior to the introduction of the guideline (implicit
      assessment). Their data were abstracted retrospectively from the medical charts.
      Main outcome measures were symptomatic VTE and major bleedings, and the
      consumption of unfractionated (UFH) and fractionated (LMWH) heparins. Follow-up
      lasted until 90 days after hospital discharge. RESULTS: Symptomatic VTE occurred
      in 5/686 (0.7%) patients of group 1 vs 9/622 (1.4%) patients of group 2 during
      the hospital phase (p>0.05), and in 9/646 (1.4%) vs 10/572 (1.7%) during the
      whole study period (p>0.05). In group 1, 350 (51%) patients did not qualify for
      thromboprophylaxis according to the guideline, and none of them experienced any
      symptomatic VTE event. Three patients (0.5%) in group 1 and 4 patients (0.6%) in
      group 2 experienced a major bleeding event (p>0.05). Average consumption of UFH
      and LMWH did not differ between the groups. CONCLUSIONS: The introduction of a
      guideline for explicit assessment of thromboembolic risk was not significantly
      superior to the formerly used implicit assessment. However, based on the small
      number of events observed in this study, a minor advantage cannot be ruled out.
      Targeted indication for thromboprophylaxis, whether explicit or implicit, avoided
      application of UFH or LMWH in half of the patients in our setting.

PMID- 15971116
TI  - Hepato-atrial anastomosis, the "other Senning operation" for treatment of Budd
      Chiari syndrome.
AB  - A now 36-year-old woman developed a suprahepatic inferior vena cava stenosis, 9
      years after liver transplantation for extensive liver echinococcosis. The lesion
      was treated by percutaneous angioplasty and stenting. Five years later,
      recurrence of echinococosis with intrastent stenosis together with clinical
      symptoms, prompted surgical treatment. Hepato-atrial anastomosis was performed
      under cardiopulmonary bypass with good result.

PMID- 15971117
TI  - The benzophenanthridine alkaloid fagaronine induces erythroleukemic cell
      differentiation by gene activation.
AB  - Fagaronine, a benzophenanthridine alkaloid from Fagara zanthoxyloides Lam.
      (Rutaceae), has been tested on the erythroleukemic cell line K562 in order to
      explain some previous results on cell differentiation. In this study we showed
      that fagaronine induces a significant hemoglobinization of the human
      erythroleukemic cell line K562. This hemoglobin synthesis was accompanied by a
      strong increase of erythroid mRNA expression such as gamma- and alpha-globin, and
      PBGD, an enzyme of heme synthesis. In addition, the Epo-R transcripts were also
      stimulated indicating that cells are engaged in a maturation process. Both
      transcription factors GATA-1 and NF-E2, which play an important role in the
      regulation of genes involved in the erythroid differentiation, were also
      transcriptionally up-regulated. To elucidate the possible role of GATA-1 in the
      FAG-induced differentiation of K562 cells, we transfected reporter constructs
      containing regulatory regions of erythroid genes encompassing GATA-1 binding
      sites. After 48 hours of treatment, FAG stimulated the EPO-R and gamma-globin
      promoters by 2- to 3-fold and the promoter/enhancer region of GATA-1 gene by 3.2
      fold. A mutation within the GATA-1 binding sites strongly decreased the promoter
      activation induced by FAG. Taken together, our results represent a demonstration
      that FAG exerts its differentiating activity by a specific activation of the
      regulating GATA-1 regions of genes involved in the erythroid phenotype
      expression.

PMID- 15971118
TI  - Phenolic esters from the rhizomes of Cimicifuga racemosa do not cause
      proliferation effects in MCF-7 cells.
AB  - Five phenylpropanoid esters, caffeoylglycolic acid, 2-caffeoylpiscidic acid
      (cimicifugic acid D), 3,4-dihydroxyphenacyl caffeate (petasiphenone), 3,4
      dihydroxyphenyl-2-oxopropyl isoferulate (cimiciphenol) and 3,4-dihydroxyphenacyl
      isoferulate (cimiciphenone) were isolated from a commercially available extract
      of the rhizomes of Cimicifuga racemosa (L.) Nutt. (syn. Actaea racemosa L.) for
      the first time; the known cimicifugic acids A, B, E, F, fukinolic acid, fukiic
      acid and caffeic acid were also obtained. Cimiciphenone and caffeoylglycolic acid
      are new natural products. The structures were elucidated by means of
      spectroscopic data (ESI-MS, 1H-, 13C-NMR, COSY, HMQC, HMBC and NOE experiments).
      Ferulic acid and isoferulic acid were detected by HPLC analysis in comparison to
      standards. The estrogenic activity of the isolated compounds was tested in an
      estrogen-dependent MCF-7 mamma carcinoma cell line; 17beta-estradiol (10(-11) M)
      and the phytoestrogen coumestrol (10(-7) - 10(-5) M) were used as references. The
      results suggest that, in contrast to an earlier report, the phenolic esters do
      not exert a proliferative (estrogenic) effect in this test system.

PMID- 15971119
TI  - Induction of apoptosis by Panduratin A isolated from Kaempferia pandurata in
      human colon cancer HT-29 cells.
AB  - We previously showed that panduratin A isolated from an extract of Kaempferia
      pandurata (Zingiberaceae) was a strong inhibitor of cyclooxygenase-2 (COX-2) in
      RAW264.7 cells, suggesting a potential use of panduratin A as an anti
      inflammatory agent. In the present study, we have investigated the effects of
      panduratin A on cytoplasmic levels of COX-2, as well as proliferation and
      apoptosis in human colon cancer cells HT-29. Cell proliferation and induction of
      apoptosis was determined by the MTT assay, DNA fragmentation measurement, flow
      cytometric analysis, nuclear staining and Western blotting. The MTT assay
      indicated that panduratin A exhibited cytotoxicity with an IC50 value of 28
      microM. The cytotoxic effects of panduratin A were found to be accompanied by the
      dose-dependent induction of apoptosis as assessed by DNA fragmentation and
      apoptotic bodies. In addition, treatment with an apoptosis-inducing concentration
      of panduratin A resulted in cleavage of poly(ADP-ribose) polymerase (PARP) with a
      concomitant decrease in procaspase-3 protein. Our study provides evidence for
      cell growth inhibition and induction of apoptosis by panduratin A in human colon
      cancer cells, suggesting its potential use as a cancer chemopreventive and
      therapeutic agent.

PMID- 15971120
TI  - Protective effect of (S)-bakuchiol from Psoralea corylifolia on rat liver injury
      in vitro and in vivo.
AB  - The aim of this study was to investigate the protective effect of (S)-bakuchiol
      isolated from the seed of Psoralea corylifolia, on liver injury. Primary rat
      hepatocyte intoxication was induced by tert-butyl hydroperoxide (tBH), carbon
      tetrachloride (CCl4) or D-galactosamine (D-GalN). Liver injury was induced by
      either CCl4 or D-GalN in rats. In vitro, the cellular leakage of lactate
      dehydrogenase and cell viability following treatment with hepatotoxicants were
      significantly improved by bakuchiol treatment at a concentration range of 25-200
      microM for tBH, 100-200 microM for CCl4 and 100-200 microM for D-GalN-induced
      hepatocyte injury. Treatment with bakuchiol significantly inhibited lipid
      peroxidation and intracellular glutathione depletion in hepatocytes induced by
      tBH, CCl4 or D-GalN. Treatment with bakuchiol (25 or 50 mg/kg, p.o.) at 1, 24 and
      48 h after subcutaneous injection of CCl4 significantly reduced the levels of
      aspartate transaminase and alanine transaminase in serum. Histological
      observations revealed that fatty acid changes, hepatocyte necrosis and
      inflammatory cell infiltration in CCl4-injured liver was improved when treated
      with bakuchiol. Bakuchiol treatment (25 and 50 mg/kg, p.o.) also significantly
      reduced the levels of aspartate transaminase and alanine transaminase in an acute
      liver injury model induced by D-GalN. From these results, bakuchiol has a
      protective effect against tBH, CCl4 or D-GalN-induced hepatotoxicity in vitro or
      in vivo.

PMID- 15971121
TI  - Laxifolone A suppresses LPS/IFN-gamma-induced NO synthesis by attenuating NF
      kappaB translocation: role of NF-kappaB p105 level.
AB  - Laxifolone A is a triterpene isolated from Euonymus laxiflorus Champ. Exposure of
      RAW264.7 macrophages to laxifolone A concentration-dependently suppressed
      lipopolysaccharide/interferon-gamma (LPS/IFN-gamma)-induced nitrite production
      (IC50 = 0.37 +/- 0.05 microM), inducible NO synthase (iNOS) protein, and iNOS
      mRNA expression. Translocation of nuclear factor-kappaB (NF-kappaB) into the
      nucleus with subsequent activation of iNOS gene transcription is essential in NO
      signaling. Western blot analysis indicated that the cytosolic NF-kappaB/p65 was
      obviously decreased after LPS/IFN-gamma stimulation for 30 min and this
      phenomenon could be reversed by laxifolone A. Similarly, a time-related NF
      kappaB/p65 nuclear translocation induced by LPS/IFN-gamma was diminished in the
      presence of laxifolone A. However, laxifolone A failed to interfere in LPS/IFN
      gamma-evoked IkappaB degradation. Our results also showed that LPS/IFN-gamma
      stimulation resulted in the degradation of NF-kappaB p105, the NF-kappaB
      precursor, and laxifolone A treatment significantly counteracted this effect.
      Furthermore, laxifolone A itself was able to enhance NF-kappaB p105 protein
      expression. In summary, these results suggest that inhibition of NF-kappaB p105
      degradation in cytoplasm may participate in the abrogation of LPS/IFN-gamma
      induced NF-kappaB translocation and subsequent NO synthesis by laxifolone A.

PMID- 15971122
TI  - Quercetin-induced induction of the NO/cGMP pathway depends on Ca2+-activated K+
      channel-induced hyperpolarization-mediated Ca2+-entry into cultured human
      endothelial cells.
AB  - Quercetin is one of the dietary-derived flavonoids that are held responsible for
      the beneficial effects of red wine drinking in coronary artery disease known as
      the "French paradox". We examined whether quercetin modulates endothelial
      function by influencing Ca2+-activated K+ channels with large conductance
      (BK(Ca)) in cultured human endothelial cells. Membrane potential and
      intracellular Ca2+ concentrations of cultured human endothelial cells derived
      from umbilical cord veins (HUVEC) were measured using the fluorescence dyes
      DiBAC, and FURA-2, respectively. NO production was examined using a cGMP
      radioimmunoassay. HUVEC proliferation was analyzed by cell counts and thymidine
      incorporation. A dose-dependent hyperpolarization of HUVEC was recorded when
      quercetin was added (5-100 micromol/L). The maximum effect (50 micromol/L) was
      significantly reduced by the addition of the highly selective BK(Ca) inhibitor
      iberiotoxin (100 nmol/L), but not by blockers of other Ca2+-activated K+ channels
      (n = 30; p < 0.05). This BK(Ca)-induced hyperpolarization caused a transmembrane
      Ca2+ influx, because the quercetin-induced increase of intracellular Ca2+ was
      blocked by iberiotoxin, or by applying 2-aminoethoxydiphenylborate (100
      micromol/L)--an inhibitor of capacitative Ca2+ entry (n = 30; p < 0.05).
      Quercetin-induced cGMP levels were significantly reduced by the eNOS-inhibitor l
      NMMA (300 micromol/L), and by iberiotoxin (n = 10; p < 0.05). Endothelial
      proliferation was significantly reduced by 56 % when cells were incubated with
      quercetin (n = 12; p < 0.05). This effect was due to the increased NO production,
      because it was reversed when the cells were treated with a combination of
      quercetin and l-NMMA. In conclusion quercetin improves endothelial dysfunction by
      increasing NO synthesis involving BK(Ca)-dependent membrane hyperpolarization
      induced capacitative Ca 2+ entry. Increased NO production is responsible for the
      quercetin-dependent inhibition of endothelial proliferation.

PMID- 15971123
TI  - Molecular mechanism of the inhibitory effect of trilinolein on endothelin-1
      induced hypertrophy of cultured neonatal rat cardiomyocytes.
AB  - Trilinolein, isolated from the traditional Chinese herb Sanchi ( Panax
      notoginseng), has been shown to have myocardial protective effects via its
      antioxidant ability. However, the cellular and molecular mechanisms of the
      protective effect of trilinolein in the heart remain to be elucidated. Oxidative
      mechanisms have been implicated in neonatal cardiomyocyte hypertrophy. We
      therefore have examined whether trilinolein attenuates reactive oxygen species
      (ROS) production and thus ET-1-induced hypertrophy of cardiomyocytes. Cultured
      neonatal rat cardiomyocytes were stimulated with ET-1 (10 nM), [3H]leucine
      incorporation and the beta-myosin heavy chain (beta-MyHC) promoter activity were
      examined. Trilinolein (1 and 10 microM) inhibited the ET-1-induced increase of
      [3H]-leucine incorporation in a concentration-dependent manner. Trilinolein (1
      and 10 microM) also inhibited ET-1-induced beta-MyHC promoter activity in
      cardiomyocytes. We further examined the effects of trilinolein on ET-1-induced
      intracellular ROS generation by measuring a redox-sensitive fluorescent dye,
      2',7'-dichlorofluorescin diacetate, fluorescence intensity. Trilinolein (1 and 10
      microM) inhibited ET-1-increased intracellular ROS levels in a concentration
      dependent manner. This increase of ROS by ET-1 (10 nM) or H2O2 (25 microM) was
      significantly inhibited by trilinolein (10 microM) and N-acetylcysteine (10 mM).
      Moreover, ET-1- or H2O2-induced beta-MyHC promoter activity and protein synthesis
      were also inhibited by trilinolein (10 microM). These data indicate that
      trilinolein inhibits ET-1-induced beta-MyHC promoter activity, and subsequent
      hypertrophy via its antioxidant ability in cardiomyocytes.

PMID- 15971124
TI  - 13C-labelling of xanthohumol in hop cones (Humulus lupulus).
AB  - Biolabelling conditions in hop cones of xanthohumol (Xn) were studied by feeding
      [U-13C]glucose, [1-13C]glucose, [ring-13C6]phenylalanine, [2-13C]sodium acetate
      or [2-13C]malonic acid as biosynthetic precursors to hop sprouts. Quantitative
      13C-NMR spectroscopic analysis of the resulting labelled Xn showed different
      labelling patterns and ratios depending on precursor and feeding concentrations.
      The highest incorporation rate was achieved with [U-13C]glucose (9.41 +/- 1.22
      %). With [ring-13C6]phenylalanine only ring B was labelled (3.51 +/- 0.08 %
      enrichment). [2-13C]sodium acetate and [2-13C]malonic acid allowed labelling of
      the A-ring (1.82 +/- 0.02 % and 1.74 +/- 0.03 % enrichment). The specific
      labelling pattern of the prenyl side chain with [1-13C]glucose (2.36 +/- 0.27 %
      enrichment) confirmed the biosynthetic origin to be MEP pathway-derived. On the
      basis of these results radiolabelling of Xn will be performed for in vivo
      bioavailability studies.

PMID- 15971125
TI  - New cytotoxic cyclobutanoid amides, a new furanoid lignan and anti-platelet
      aggregation constituents from Piper arborescens.
AB  - Three new cyclobutanoid amides with trans-trans-trans configurations,
      piperarborenine C, piperarborenine D and piperarborenine E, and a new furanoid
      lignan, (+)-arborone, together with twelve known compounds, were isolated from
      the stems of Piper arborescens. The structures of these new compounds were
      determined by means of spectral analyses. Piperarborenine C, (+)-diayangambin,
      piplartine, piperolactam B, piperolactam C, aristolactam BIII, goniothalactam,
      and methyl trans-3,4,5-trimethoxycinnamate possessed anti-platelet aggregation
      activity in vitro. Among them, piplartine showed the most potent anti-platelet
      aggregation activity induced by collagen and showed an IC50 value of 21.5 microM.
      Piperarborenines A - E, piperarborenine, aristololactam BIII and goniothalactam
      showed significant cytotoxic activity (IC50 values < 4 microg/mL) against P-388,
      HT-29 and A549 cell lines in vitro.

PMID- 15971126
TI  - New sesquiterpenes from Sonchus transcaspicus.
AB  - Four new eudesmanolides were isolated from the whole plant of Sonchus
      transcaspicus and their structures were elucidated by means of spectroscopic
      methods, including 2D-NMR (1H-1H COSY, HMQC, HMBC and NOESY) and NOEDS (NOE
      difference spectra) as 1beta-O-beta-D-glucopyranosyl-5alpha,6beta H-eudesma-3-en
      12,6alpha-olide (1), 1beta-O-beta-D-glucopyranosyl-15-O-( p-hydroxyphenylacetyl)
      5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (2), 1beta-O-beta-D
      glucopyranosyl-(6'-O-p-hydroxyphenyl acetate)-15-O-(p-hydroxyphenylacetyl)
      5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (3) and 1beta-hydroxy-15-O
      (p-methoxyphenylacetyl)-5alpha,6beta H-eudesma-3,11(13)-dien-12,6alpha-olide (4).
      Compounds 1, 2 and 3 showed antibacterial activity against Escherichia coli and
      Staphylococcus aureus cells. Compounds 2 and 3 were evaluated for their in vitro
      cytotoxic activity against cultured SMMC-7721 (human hepatoma), HELA (human
      cervical carcinoma) and B-16 (murine melanoma) cells. The IC50 values for 2 were
      108.0, 161.1 and 203.0 microM and those for 3 were 74.1, 117.3 and 135.0 microM,
      respectively. The structure-activity relationship is discussed.

PMID- 15971127
TI  - Androstane and withanolides from Physalis cinerascens.
AB  - Two new withanolides, cinerolide and 24,25-dihydrowithanolide S, together with
      the new androstane, cinedione, and the known withanolides, visconolide,
      physalactone, withanolide S and 4beta-hydroxywithanolide E were isolated from the
      EtOAc extract of leaves, flowers and stems of Physalis cinerascens. The
      structures of these compounds were established by spectroscopic methods and that
      of cinerolide was confirmed by X-ray diffraction analysis.

PMID- 15971128
TI  - Antiproliferative hopane and oleanane glycosides from the roots of Glinus
      lotoides.
AB  - Three new hopane saponins, lotoidosides A - C (1 - 3), and four new oleanane
      saponins, lotoidosides D - G (4 - 7), were isolated from the roots of Glinus
      lotoides L. (Molluginaceae). Their structures were determined by extensive 1D-
      and 2D-NMR spectroscopy and ESI-MS analysis. The antiproliferative activity of
      compounds 1 - 7 was evaluated using three continuous murine and human culture
      cell lines J774.A1, HEK-293, WEHI-164. Compounds 1 and 3 - 7 showed significant
      cytotoxicity against the three cancer cell lines with IC50 values ranging from
      0.018 to 0.62 microM, while compound 2 exerted a weak activity only against the
      cell line HEK-293.

PMID- 15971129
TI  - A biflavonoid from Luxemburgia nobilis as inhibitor of DNA topoisomerases.
AB  - The biflavonoid 2'',3''-diidroochnaflavone ( 1), isolated from the leaves of
      Luxemburgia nobilis, was cytotoxic to murine Ehrlich carcinoma (IC50 = 17.2
      microM) and human leukemia K562 cells (IC50 = 89.0 microM) in a concentration
      dependent manner in 45 h cell culture. The acetyl (1a) and methyl (1b)
      derivatives of 1 were not cytotoxic to these tumour cells at 67.0 and 82.0 microM
      concentrations, respectively. Biflavonoid 1 as well 1a inhibit the activity of
      human DNA topoisomerases I and II-alpha as observed in relaxation and
      decatenation assays. In addition, we show that 1 is a DNA interacting agent,
      which causes DNA unwinding in an assay with topoisomerase I. Also,
      spectrophotometric titration of 1 with DNA resulted in a pronounced hypochromic
      effect.

PMID- 15971130
TI  - Mechanism of inhibition of peroxynitrite-induced oxidation and nitration by [6]
      gingerol.
AB  - [6]-Gingerol potently inhibits peroxynitrite-induced oxidation and nitration
      reactions, but its mechanism of action is unclear. In order to discover the
      mechanism of inhibition, [6]-gingerol was reacted with peroxynitrite and the
      reaction mixture was analyzed using HPLC. The HPLC chromatogram showed one novel
      peak, indicative of the formation of a reaction product between [6]-gingerol and
      peroxynitrite. This compound was purified and identified as a symmetrical dimer
      of [6]-gingerol covalently linked at the aromatic ring. It has been assumed that
      this dimer is generated from a phenoxyl radical intermediate produced from [6]
      gingerol via one-electron oxidation by peroxynitrite-derived radicals. We propose
      a mechanism in which [6]-gingerol scavenges peroxynitrite-derived radicals and
      consequently inhibits peroxynitrite-induced oxidation and nitration reactions.

PMID- 15971131
TI  - Isolation of a new saponin and cytotoxic effect of saponins from the root of
      Platycodon grandiflorum on human tumor cell lines.
AB  - A novel triterpenoid saponin, deapioplatycoside E (1) was isolated from the root
      extract of Platycodon grandiflorum, together with the seven known saponins 2 - 8,
      i. e., platycoside E (2), deapioplatycodin D3 (3), platycodin D3 (4), polygalacin
      D2 (5), platycodin D2 (6), deapioplatycodin D (7) and platycodin D (8). The
      structure of the new saponin 1 was determined on the basis of spectral analysis
      and chemical evidence. The crude saponin fraction (ED50: ca. 10 - 15 microg/mL)
      and compounds 6 - 8 (ED50: ca. 4 - 18 microg/mL) exhibited significant inhibition
      on the proliferation of five kinds of cultured human tumor cell lines, i. e.,
      A549 (non-small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central
      nerve system) and HCT-15 (colon), in vitro.

PMID- 15971132
TI  - Anti-HIV bioactive stilbene dimers of Caragana rosea.
AB  - Bioassay-guided fractionation of the ethanol extract of the aerial parts of
      Caragana rosea Turcz. led to the isolation of two new (cararosinol C and
      cararosinol D) and four known [scirpusin A (1), cis-scirpusin A (2), maackin (3),
      scirpusin B (4)] stilbene dimers. This is the first identification of these
      compounds from this plant and the first time that compound 2 has been isolated as
      a natural compound. Their structures were established mainly by spectral means.
      An in vitro assay against HIV-1 (IIIB), demonstrated compounds 1 and 4 to be
      active against HIV, with EC50 values of 10 microg/mL and 7 microg/mL
      respectively.

PMID- 15971133
TI  - Cytokinin and ethylene control indole alkaloid production at the level of the
      MEP/terpenoid pathway in Catharanthus roseus suspension cells.
AB  - The Madagascar periwinkle Catharanthus roseus accumulates a number of terpenoid
      indole alkaloids, some of which have high therapeutic interest. The
      biotechnological approach with cells in vitro remains an alternative to the field
      culture of periwinkle for the production of such compounds. We previously
      reported that two phytohormones, cytokinin and ethylene, remarkably enhanced the
      accumulation of alkaloids in periwinkle cell suspensions. In this work, we
      investigated the effects of these hormones on the regulation of several genes of
      the indole alkaloid biosynthetic pathway. We show that cytokinin and/or ethylene
      greatly enhanced the expression of the geraniol 10-hydroxylase gene. When given
      together, these hormones also increased the expression of three genes belonging
      to the methyl-erythritol pathway. These results make it possible to consider
      elements of cytokinin and ethylene signalling pathways as tools for improving
      terpenoid indole alkaloid production through metabolic engineering.

PMID- 15971134
TI  - Chemical composition and antimicrobial activity of the essential oil of Artemisia
      lavandulaefolia.
AB  - The chemical components of the essential oil obtained from Artemisia
      lavandulaefolia DC. were analyzed by GC-MS. Ninety-nine compounds accounting for
      94.9 % of the essential oil were identified. The major compounds in the essential
      oil were beta-caryophyllene (16.1 %), cis-chrysanthenol (7.0 %), 1,8-cineole (5.6
      %), borneol (5.3 %), trans-beta-farnesene (5.1 %), camphor (4.9 %), yomogi
      alcohol (4.5 %), alpha-terpineol (3.9 %), and alpha-humulene oxide (3.3 %). The
      essential oil and some of its major compounds were tested for antimicrobial
      activity against 15 different genera of oral bacteria. The essential oil of A.
      lavandulaefolia exhibited considerable inhibitory effects against all obligate
      anaerobic bacteria (MIC values, 0.025 to 0.05 mg/mL; MBC values, 0.025 to 0.1
      mg/mL) tested, while its major compounds demonstrated different degrees of growth
      inhibition.

PMID- 15971135
TI  - Two new non-glycosidic iridoids from the leaves of Campsis grandiflora.
AB  - Two new non-glycosidic iridoids, which were named cachinol (1) and 1-O-methyl
      cachinol (2), were isolated from the methanol extract of the leaves of Campsis
      grandiflora together with a known iridoid cachineside I (3). The structures of
      compounds 1 and 2 were determined on the basis of spectroscopic methods including
      two dimensional NMR and high resolution mass spectrometry. All of the isolated
      compounds showed mild inhibitory activities on rat platelet aggregation.
      Compounds 1 and 3 (IC50 : 246 and 219 microM, respectively) showed about 2-fold
      higher inhibitory effects than acetylsalicylic acid (ASA, IC50: 412 microM) on
      collagen-induced aggregation. Compounds 1 and 2 (IC50: 43.2 and 38.4 microM,
      respectively) were about 2-fold more inhibitory than ASA (IC50: 75.2 microM), and
      about 4-fold more effective than their glycoside 3 (IC50: 189 microM) on AA
      induced aggregation.

PMID- 15971136
TI  - A DNA microarray for the authentication of toxic traditional Chinese medicinal
      plants.
AB  - A silicon-based DNA microarray was designed and fabricated for the identification
      of toxic traditional Chinese medicinal plants. Species-specific oligonucleotide
      probes were derived from the 5S ribosomal RNA gene of Aconitum carmichaeli, A.
      kusnezoffi, Alocasia macrorrhiza, Croton tiglium, Datura inoxia, D. metel, D.
      tatula, Dysosma pleiantha, Dy. versipellis, Euphorbia kansui, Hyoscyamus niger,
      Pinellia cordata, P. pedatisecta, P. ternata, Rhododendron molle, Strychnos nux
      vomica, Typhonium divaricatum and T. giganteum and the leucine transfer RNA gene
      of Aconitum pendulum and Stellera chamaejasme. The probes were immobilized via
      dithiol linkage on a silicon chip. Genomic target sequences were amplified and
      fluorescently labeled by asymmetric polymerase chain reaction. Multiple toxic
      plant species were identified by parallel genotyping. Chip-based authentication
      of medicinal plants may be useful as inexpensive and rapid tool for quality
      control and safety monitoring of herbal pharmaceuticals and neutraceuticals.

PMID- 15971137
TI  - Medial suralGASTROCNEMIUS muscle perforator free flap: an immediate cross-leg
      flap?
AB  - The advantage of the medial sural (GASTROCNEMIUS) muscle perforator free flap is
      that it is relatively thin, even in most obese individuals, and the donor site
      can be acceptable, if morbidity must preferably be restricted to the lower
      extremities. Unfortunately, anatomic anomalies of both the arterial and venous
      circulation are not infrequent, making this a somewhat less than perfect donor
      site in the author's total experience using this flap. Nevertheless, the
      contralateral calf skin was successfully used, as shown in a clinical example, to
      cover a transmetatarsal amputation stump. This allows the conclusion that, at
      least as a technical exercise, the medial sural (GASTROCNEMIUS) muscle perforator
      free flap as a microsurgical transfer can be used as an "immediate" cross-leg
      flap. This is reminiscent of bygone eras, where such a feat required multiple
      stages over many weeks.

PMID- 15971138
TI  - Coverage of big toe defects after wrap-around flap transfer with a free soleus
      perforator flap.
AB  - In thumb reconstruction, a wrap-around flap transfer from the big toe gives
      excellent results aesthetically and functionally; however, there may be some
      problems at the donor site, such as delayed wound healing and skin ulceration. In
      10 patients, a free soleus perforator flap was used for immediate coverage of
      defects of the big toe with wrap-around flap procedures. Eight flaps survived
      completely, and the time required for wound healing was less than 1 month. Two
      flaps developed partial necrosis and required additional skin grafts. The average
      follow-up period was 46 months. There were no patients requiring defatting of the
      flaps. There were no patient complaints, such as postoperative skin erosion or
      ulceration. All patients were satisfied with the outcome. A free soleus
      perforator flap is an available method for covering defects of the big toe after
      wrap-around flap transfer.

PMID- 15971139
TI  - Deep inferior epigastric perforator flap for foot reconstruction using an
      external pedicle.
AB  - When it is necessary to apply free flaps for foot reconstruction, the choices are
      limited. Conventionally, split-thickness skin-grafted muscle flaps and
      fasciocutaneous flaps from the back or thigh have been two major options, but
      these methods take substantial time to wearing normal shoes. As an alternative,
      the authors use the deep inferior epigastric perforator (DIEP) flap with an
      external pedicle. After elevation and thinning of the flap, the vascular pedicle
      is anastomosed at a site distant from the skin defect of the foot. About 20 days
      after that, the pedicle is severed, and the skin island is trimmed and sutured.
      This method provides thin and wide coverage within a limited time, and donor-site
      morbidity is minimal both functionally and aesthetically.

PMID- 15971140
TI  - Patellar tendon reconstruction using a free latissimus dorsi flap following
      resection of a prepatellar myxofibrosarcoma: case report.
AB  - The authors' experience indicates that good functional results are achievable in
      cases with wide resection of the knee extensor mechanism. They report a low-grade
      myxoid fibrosarcoma patient in whom a one-stage functional reconstruction was
      carried out by transfer of a free latissimus dorsi flap without secondary
      surgical procedures.

PMID- 15971141
TI  - Internal mammary perforators: a cadaver study.
AB  - Microsurgeons currently employ the internal mammary artery and vein as recipient
      vessels for microvascular reconstruction of the breast with increasing frequency.
      Recent reports have demonstrated that the perforating branches of the internal
      mammary artery and vein can also be used as recipient vessels. The purpose of the
      following cadaver study was to determine the location and diameter of these
      internal mammary perforators and whether they are suitable as recipient vessels.
      Ten fresh cadavers were obtained for this project. Using a micrometer under loupe
      magnification, bilateral measurements were taken of the perforators from the
      first five interspaces. The largest arterial perforator averaged 1.74 mm in
      diameter and the largest venous perforator averaged 1.78 mm in diameter. The
      largest perforators were most commonly found in the second interspace. Based on
      the results of this study, the internal mammary perforators appear to have
      suitable diameter for microvascular anastomosis and should be considered.

PMID- 15971142
TI  - Regeneration through nerve isografts is independent of nerve geometry.
AB  - Investigators have theorized that tortuosity in nerve grafts may adversely affect
      nerve regeneration. This study investigated the effect of graft configuration and
      redundancy on regeneration across 2.5-cm rat sciatic nerve isografts. Thirty-two
      Lewis rats were randomized to four nerve grafting groups defined by gap distance
      and isograft conformation. In Group 1, grafts were interposed into a 2-cm gap,
      resulting in mild graft redundancy. In Groups 2 and 3, grafts were tacked in
      sinusoidal or omega-shaped configurations, respectively, to bridge a 0.5-cm gap.
      In Group 4, grafts were interposed after 1 cm of native sciatic nerve was
      resected, resulting in no graft redundancy and an interstump distance of 2.5 cm.
      At 6 weeks, nerve tissue was harvested; subsequent histomorphometric analysis
      revealed no significant differences in regeneration between groups. These data
      suggest that regeneration through isografts is independent of the graft geometry
      and redundancy.

PMID- 15971143
TI  - Using methylprednisolone to supplement direct current electrical field in
      promoting spinal-cord regeneration.
AB  - In order to compensate for the fact that direct current electrical fields could
      not reduce or correct spinal-cord edema after trauma, methylprednisolone was used
      2 hr after spinal-cord injury to promote the efficacy of the direct current
      electrical field. Thirty-three dogs were randomly divided into three groups and
      their spinal cords were injured with the Allen method (weight-dropping
      technique). Group A, a control group; Group B, implantation of an electrical
      stimulator 6 hr after spinal-cord injury; and Group C, given an injection of a
      large dose of methylprednisolone 2 hr after injury. Electric stimulators were
      implanted into the dogs' bodies 6 hr post-injury. The nerve functions, evoked
      potential cortical somatosensory and three kinds of nerve morphometric changes,
      were observed 1 to 3 months after injury. The indexes of Groups B and C were much
      better than Group A (p<0.05). The results in Group C were better than in Group B.
      Differences were statistically significant. The combination of direct current
      electrical field and an injection of a large dose of methylpredwisolone could
      effectively treat spinal cord injury, promoting earlier recovery of nerve
      function.

PMID- 15971144
TI  - Repair of partial lesions with nerve grafting methods in the rat tibial nerve.
AB  - A partial nerve lesion and associated neuroma can be either left alone or
      repaired with a graft. A by-pass graft around the undisturbed lesion with end-to
      side attachments might be a good alternative. This study in rats examines these
      strategies using walking-track analysis, muscle weights, and histology. After a
      tibial nerve partial lesion (3 mm) and a 21-day delay, the reexposed lesion was
      either not repaired, repaired with an interposed allograft, or a by-pass
      allograft. Functional results showed that all three groups had a steady
      improvement over the 8-week period, but without significant group differences.
      Gastrocnemius muscle ratios reflected intermediate atrophy. Axons regenerating
      through the lesion were more advanced than those which regenerated through the
      grafts and a neuroma was absent. The partial lesion can regenerate to an
      intermediate level without any intervention, including a by-pass graft, although
      the delayed repair strategy may have counteracted any potential benefits.

PMID- 15971145
TI  - Nerve repair using a vein graft filled with collagen gel.
AB  - It has been shown that a vein graft provides a good environment for axon
      regeneration in short nerve gaps. But the use of a vein graft for long nerve gaps
      is controversial because veins may collapse, due to their thin walls, and the
      surrounding scar tissue can cause constriction. In an attempt to improve results
      using the vein graft, the authors conducted the reported experiment by filling
      the lumen of the vein with collagen gel. A 15-mm rabbit peroneal nerve defect was
      bridged with a collagen-filled vein graft. On the contralateral side, the defect
      was bridged with the vein alone. When the regenerated tissue was examined 4
      weeks, 8 weeks, and 12 weeks after grafting, the number and diameter of
      myelinated fibers were significantly increased, compared with the control group
      without collagen gel. This study found that in order to increase the efficacy of
      a vein graft for axonal regeneration, collagen gel might be an appropriate matrix
      material with which to fill the vein graft.

PMID- 15971146
TI  - Enhancement of ischemic flap survival by prefabrication with transfer of
      exogenous PDGF gene.
AB  - Treatment of skin flaps by means of gene therapy has been introduced recently as
      a novel approach to enhance viability of ischemic skin flaps. Transfer of the
      platelet-derived growth factor (PDGF) to enhance survival of the ischemic skin
      flap has not been explored. In this study, the authors investigated the effect of
      the transfer of the PDGF cDNA on survival and vascularity of the ischemic random
      flap in a rat model, and compared the effects of PDGF gene therapy to those of
      vascular endothelial growth factor (VEGF) gene therapy. A total of 45 adult
      Sprague-Dawley rats were randomly divided into four groups. The PDGF gene therapy
      group (n=10) received the plasmid containing the PDGF cDNA with liposome injected
      to the dermis of the flap. A saline control group (n=10) received physiologic
      saline only, and the vector control group (n=10) received liposome plus vector
      without the PDGF gene segment. In the fourth group (n=15), the VEGF gene was
      transferred to the flap. Seven days later, a dorsal random flap including the
      injection area was raised. One rat each from the saline and vector control groups
      died during the study period and were excluded. The viability of the flap and
      vascularity within the flaps were assessed 7 days after flap elevation. The PDGF
      plasmid-treated flaps had significantly greater survival area (60.8+/-7.8
      percent) compared with the flaps treated with saline (52.3+/-5.0 percent) and
      those treated with liposome and vector (50.7+/-5.9 percent). PDGF gene therapy
      had effects on survival of the flap similar to VEGF gene therapy (57.6+/-5.2
      percent, after transfer of VEGF cDNA). Neovascularization with the flap tissues
      was confirmed by immunohistochemical staining of von Willebrand factor, a marker
      specific for angiogenesis. The number of newly-formed blood vessels in the
      transgenic flaps was significantly greater than that of the vessels in the flaps
      receiving the saline. The findings of this study indicate that transfer of the
      PDGF cDNA effectively enhances neovascularization of the ischemic skin flap and
      increases the viability of the flap, and transfer of the PDGF gene is as
      efficient as transfer of the VEGF gene in improving viability of the skin flap.
      This study suggests that PDGF gene therapy may be a novel strategy for the
      treatment of ischemic skin flaps.

PMID- 15971147
TI  - Expression of the rat renal PiT-2 phosphate transporter.
AB  - BACKGROUND: NaPi-2a is the main sodium-dependent Pi (Na+-Pi) transporter in the
      apical membrane of the renal proximal tubule. Another group of Pi transporters,
      Glvr-1 (PiT-1) and Ram-1 (PiT-2), was identified. The PiT-2 cRNA induces Na+
      dependent Pi uptake into Xenopus laevis oocytes. Prior studies have revealed the
      presence of the Pit-2 transporter in the kidney. OBJECTIVES: Further
      characterization of the PiT-2 transporter in the kidney and assessment of its
      developmental regulation. METHODS: Using primers specific for the PiT-2 mRNA and
      an antibody specific for the PiT-2 protein, we assessed the expression and
      developmental regulation of the renal PiT-2 mRNA and protein. RESULTS: RT-PCR
      analysis revealed that a 182 bp product was evident in the total kidney (TK),
      cortex (C), and medulla (M). Northern blots demonstrated a PiT-2 mRNA of
      approximately 4 kb (expected size) in the TK, C, and M. PiT-2 mRNA expression was
      similar in all kidney regions. RT-PCR and Northern blot analysis revealed that
      the PiT-2 cDNA was highly abundant in OK and MDCK culture cells. RT-PCR and
      Northern blot analysis revealed expected products at all ages studied.
      Densitometry demonstrated similar levels of expression of PiT-2 mRNA in the
      kidneys of older versus younger animals, and persistent expression in elderly
      rats. The PiT-2 protein was present in the TK, C, and M, and in OK and MDCK
      cells. PiT-2 protein abundance was similar at all ages studied. CONCLUSIONS:
      These studies further characterize the renal PiT-2 transporter and show that its
      expression is stable throughout development and ageing.

PMID- 15971148
TI  - Possible involvement of phosphatidylinositol 3-kinase/Akt pathway in insulin-like
      growth factor-I-induced alkaline phosphatase activity in osteoblasts.
AB  - In the present study, we investigated whether Akt is involved in insulin-like
      growth factor-I (IGF-I)-stimulated activity of alkaline phosphatase, a marker of
      mature osteoblast phenotype, in osteoblast-like MC3T3-E1 cells. IGF-I induced the
      phosphorylation of Akt in these cells. Akt inhibitor significantly suppressed the
      IGF-I-stimulated alkaline phosphatase activity. The phosphorylation of Akt
      induced by IGF-I was reduced by the Akt inhibitor. LY294002 and wortmannin,
      inhibitors of phosphatidylinositol 3-kinase, significantly suppressed the IGF-I
      induced alkaline phosphatase activity. The phosphorylation of Akt induced by IGF
      I was markedly reduced by LY294002 and wortmannin. These results strongly suggest
      that phosphatidylinositol 3-kinase/Akt plays a role in the IGF-I-stimulated
      alkaline phosphatase activity in osteoblasts.

PMID- 15971149
TI  - Participation of protein kinases in the stimulant action of GLP-1 on 2-deoxy-D
      glucose uptake by normal rat skeletal muscle.
AB  - Several protein kinases were recently proposed for involvement in GLP-1
      stimulated D-glucose transport in skeletal muscle from both normal subjects and
      type 2 diabetic patients. This study was mainly aimed at investigating the effect
      of potential inhibitors of distinct protein kinases and protein phosphatase-1
      upon insulin- and GLP-1-stimulated 2-deoxy-D-glucose net uptake by normal rat
      skeletal muscle. The basal uptake of the D-glucose analog was decreased by
      wortmannin--a phosphatidylinositol-3-kinase inhibitor--, PD98059--a mitogen
      activated protein kinases inhibitor--, and TNFalpha--a protein phosphatase-1
      inhibitor--, but not by either rapamycin--a p70s6 kinase inhibitor--, or H-7--, a
      protein kinase C inhibitor--. The enhancing action of both insulin and GLP-1 upon
      2-deoxy-D-glucose transport was abolished by PD98059 and H-7, but largely
      unaffected by TNFalpha. Wortmannin and rapamycin preferentially affected the
      response to GLP-1 and insulin, respectively. These findings thus document both
      analogies and dissimilarities in the participation of the concerned enzymes in
      the stimulant action of insulin versus GLP-1 upon D-glucose transport in normal
      rat skeletal muscle.

PMID- 15971150
TI  - Angiotensin II stimulates cardiac adrenomedullin production and causes
      accumulation of mature adrenomedullin independently of hemodynamic stress in
      vivo.
AB  - Adrenomedullin is a potent hypotensive peptide that may act on myocytes to
      inhibit hypertrophy and on fibroblasts to inhibit growth in vitro induced by
      mechanical stretching and angiotensin II. Adrenomedullin is processed from the
      inactive intermediate adrenomedullin precursor with a glycine extension, which is
      subsequently converted to biologically active mature adrenomedullin by enzymatic
      amidation. Total adrenomedullin is the sum of intermediate and mature
      adrenomedullin. We examined the effect of a subpressor dose of angiotensin II on
      the production of left ventricular adrenomedullin and on protein levels of mature
      adrenomedullin in the left ventricle in vivo. We also investigated whether the
      effect is mediated by the angiotensin II type 1 receptor. Concentrations of total
      and mature adrenomedullin in the left ventricle and mature adrenomedullin-to
      intermediate adrenomedullin ratio were significantly increased by angiotensin II
      infusion, regardless of pressure overload. Total and mature adrenomedullin
      concentrations significantly correlated with the weight of the left ventricle.
      Furthermore, increased adrenomedullin gene expression and protein levels were
      completely suppressed by a subdepressor dose of angiotensin II type 1 receptor
      blocker. In conclusion, angiotensin II stimulates the production of cardiac
      adrenomedullin and accumulates mature adrenomedullin in the left ventricle
      independently of hemodynamic stress. These processes are partially regulated
      through the angiotensin II type 1 receptor in vivo.

PMID- 15971151
TI  - Dopaminergic influence on thyrotropin secretion in primary hypothyroidism.
AB  - This study was conducted to assess the influence of dopamine on thyrotropin
      secretion in patients with primary hypothyroidism before and after optimized L
      thyroxin replacement therapy. Thyrotropin responses to dopamine infusion (4
      microg/kg/min over 3 hours) and IV metoclopramide (10 mg bolus), a dopamine
      receptor blocker were studied in 25 consecutive patients with primary
      hypothyroidism before and after achieving stable euthyroid state and compared
      with 15 normal age-matched controls. Thyrotropin response to both dopamine
      infusion (decremental) and IV metoclopramide bolus (incremental) was greater in
      patients with primary hypothyroidism than that in the control subjects.
      Thyrotropin response was greater in women than in men. The magnitude of
      decremental thyrotropin response to dopamine infusion and the incremental
      response to IV metoclopramide bolus significantly correlated with the basal T3
      and T4 levels. Thyrotropin response was blunted to dopamine infusion but not to
      metoclopramide at follow-up after six-month replacement with L-thyroxin, and both
      the responses were comparable in women and men in patient group. We conclude that
      modulation of dopaminergic system by dopamine or by dopamine receptor blocker has
      a greater influence on thyrotropin secretion in patients with primary
      hypothyroidism than euthyroid normal subjects.

PMID- 15971152
TI  - Heterogeneous forms of immunoreactive galanin in human plasma; higher levels in
      men than in women.
AB  - Galanin, a neuropeptide, has important effects on hormone secretion from the
      hypothalamus and pituitary, and may also be involved in important biological
      processes such as pain, memory, and food intake. Yet, there is limited knowledge
      about how these processes are reflected by circulating galanin. To study the
      levels and molecular forms of galanin in the human circulation, plasma was
      analysed from 27 healthy subjects, 14 women and 13 men, using two extraction
      methods and a specific radioimmunoassay for human galanin. After extraction on
      Sep Pak C-18 columns, plasma galanin-like immunoreactivity (galanin-LI) in the
      healthy men was 6.3 +/- 2.5 pmol/l (mean +/- SD, n = 12), which was higher than
      in the women, 4.1 +/- 1.5 pmol/l (n = 14, p = 0.010). A small increase in galanin
      LI was seen with age in the women (r = 0.54, p < 0.05) but there was no
      significant difference between pre- and postmenopausal women. Galanin
      immunoreactivity after Sep Pak and immunoextraction correlated (r = 0.74, p <
      0.001) the levels being higher after immunoextraction (p < 0.001). Gel
      chromatography disclosed heterogeneity of circulating galanin-LI with the
      majority eluting as homologs with a molecular weight higher than synthetic human
      galanin. Homologs smaller than galanin were also found. Sep Pak C-18 extraction
      eliminated the majority of the higher molecular forms. In conclusion, circulating
      galanin-LI was found to be higher in men and to be present mainly as molecular
      forms larger than synthetic galanin.

PMID- 15971153
TI  - Adiponectin is associated with bone mineral density in perimenopausal women.
AB  - The aim of the current investigation was to investigate any potential effect of
      fasting plasma adiponectin concentration on bone tissue, and to find possible
      relationships of fasting plasma adiponectin level with different body
      composition, insulin sensitivity and physical performance parameters in a group
      of healthy perimenopausal women. Twenty-one premenopausal and 17 early
      postmenopausal women participated in this study. The women were matched for body
      mass index (BMI) and level of mean daily energy expenditure. Women had similar
      adiponectin (8.4 +/- 3.9 vs. 9.9 +/- 5.4 microg/ml) and leptin values (12.0 +/-
      7.7 vs. 14.0 +/- 8.2 ng/ml) before and after menopause. Significant relationships
      were observed between plasma adiponectin and bone mineral content, total bone
      mineral density (BMD) and lumbar spine BMD values (r > - 0.36; p < 0.05).
      Furthermore, adiponectin had a significant negative association with total BMD
      (beta = - 1.228; p = 0.004) and lumbar spine BMD (beta = - 0.312; p = 0.005)
      independent of the influence that other measured body compositional, hormonal or
      physical performance factors may exert on BMD. Adiponectin was also significantly
      related to waist-to-hip ratio (WHR) (beta = - 2.300; p = 0.002) and fasting
      insulin resistance index (FIRI) (beta = - 0.006; p = 0.007) in separate
      regression models. No relationship was observed between leptin and measured bone,
      physical performance and insulin resistance values. Leptin significantly
      correlated to BMI (beta = 0.018; p = 0.034), lean body mass (beta = 0.025; p =
      0.024) and fat mass (beta = 0.019; p = 0.001) in separate regression models. In
      conclusion, the results of present study show that circulating adiponectin
      appears to exert an independent effect on BMD in perimenopausal women and may
      represent a link between adipose tissue and bone mineral density.

PMID- 15971154
TI  - Arabinoxylan-enriched meal increases serum ghrelin levels in healthy humans.
AB  - Soluble fibre like arabinoxylan (AX) is thought to have beneficial effects on
      metabolism. In this study, we investigated the effect of a breakfast enriched in
      AX fibre on glucose, insulin and ghrelin values. AX-enriched and control
      breakfasts were served to fifteen young volunteers (nine female, six male).
      Glucose, insulin and ghrelin responses were measured after the meal. To avoid
      effects from differences in glucose metabolism, further analysis was restricted
      to those subjects with known normal glucose regulation (seven female, four male).
      The AX fibre-enriched breakfast did not significantly change glucose levels for
      two hours after breakfast, but decreased insulin levels in the entire cohort (p =
      0.035). Glucose response was also not significantly different in subjects with
      normal glucose regulation (p = 0.367), and the insulin responses after an AX
      enriched breakfast showed only a tendency towards lower values (p = 0.065).
      Nevertheless, plasma ghrelin two hours after AX-enriched breakfast was higher
      than after the control meal (396.1 +/- 36.4 pg/ml vs. 328.3 +/- 32.6 pg/ml, p <
      0.001). In subjects with normal glucose regulation, the AX-enriched breakfast
      increased ghrelin levels without any significant difference in glucose or insulin
      response. This effect is therefore unlikely to be mediated by insulin, but the
      underlying mechanism remains to be elucidated.

PMID- 15971155
TI  - Soy protein influences insulin sensitivity and cardiovascular risk in male lean
      SHHF rats.
AB  - Previous investigations have demonstrated a marked effect of soy protein on
      multiple physiological parameters associated with the metabolic syndrome (MS).
      This preliminary study investigated the physiological effects of soy-based diets
      on cardiovascular risk in a unique rodent model that reflects early stages of MS.
      Briefly, lean male SHHF (+/cp) rats were randomly assigned to the following
      treatment groups: casein (control, C); low-isoflavone (LIS) soy protein isolate;
      high-isoflavone (HIS) soy protein isolate; or C+ 0.01 % rosiglitazone (CR). Rats
      were fed for thirty-six weeks. Liver weight, heart weight, total plasma
      cholesterol, fasting blood glucose were lower in soy-fed animals compared to
      control (p < 0.01). Body weight, kidney weight, alanine aminotransferase (ALT),
      fasting plasma insulin, and homeostasis model assessment (HOMA) score were also
      lower in LIS-fed rodents (p < 0.05) compared to casein treatment. All diet groups
      exhibited lower urine protein (p < 0.01) and small arteriole content (p < 0.05)
      compared to controls. LIS feed had a slightly more profound influence on body
      weight, liver metabolism, and insulin sensitivity. However, both soy diets
      exhibited marked improvements over a casein-based diet.

PMID- 15971156
TI  - Soy protein influences the development of the metabolic syndrome in male obese
      ZDFxSHHF rats.
AB  - Previous investigations have demonstrated a marked effect of soy protein on the
      metabolic syndrome (MS). The purpose of this preliminary study was to identify
      the effects of soy-based diets on male obese ZDFxSHHF (fa/ fa-cp/?) rats. Animals
      were randomly assigned to one of four diets: control, casein (C); low-isoflavone
      (LIS) soy protein; high-isoflavone (HIS) soy protein; or casein + rosiglitazone
      (CR). Physiological, biochemical, and molecular parameters were determined at
      sacrifice. Body weight (p < 0.01) and food intake (p < 0.05) were lower in LIS
      fed rodents. Rosiglitazone-treated animals had higher body weight and adiposity
      (p < 0.05). LIS and CR groups exhibited better glycemic control (p < 0.05), but
      with a limited effect in rosiglitazone-treated animals. HIS fed rats had higher
      glucose and triacylglyceride levels (p < 0.01), and lower plasma insulin (p <
      0.01). Renal function parameters with the exception of an increase in systolic
      blood pressure (p < 0.05) were all suppressed in the LIS group (p < 0.01). The CR
      group had twofold PPARalpha and PPARgamma mRNA abundance (p < 0.01). LIS-fed
      animals also exhibited greater abundance of PPARgamma mRNA (p < 0.001), and
      nearly threefold FAS and CPT-1 mRNA levels (p < 0.05). HIS-fed rats also had
      higher abundance of CPT-1 mRNA, as well as a lower abundance of ACC mRNA (p <
      0.05). Soy-based diets, influenced by isoflavone content and distinct from
      rosiglitazone, improved several metabolic parameters in obese ZDFxSHHF rats.

PMID- 15971157
TI  - Secretin-stimulated amylase release into blood is impaired in type 1 diabetes
      mellitus.
AB  - BACKGROUND: Prior studies have provided data indicating the existence of close
      interaction between pancreatic endocrine and exocrine function, but few clinical
      studies have explored this relationship in depth. We compared pancreatic exocrine
      function non-endoscopically in individuals with type 1 diabetes mellitus, type 2
      diabetes mellitus, and normal glucose tolerant controls, to assess the importance
      of local insulin production to pancreatic exocrine function. METHODS: The plasma
      amylase response to intravenous secretin challenge was measured in men with type
      1 diabetes mellitus (n = 5), type 2 diabetes mellitus (n = 5), and normal
      controls (n = 3). Patients were characterized by their urinary excretion of c
      peptide and albumin over 24 hours. Autonomic neuropathy was non-invasively
      assessed by measuring RR variation (with deep respiration on EKG). RESULTS: Post
      secretin amylase responses were generally absent with low baseline levels in the
      patients with type 1 diabetes mellitus. Patients with type 2 diabetes mellitus
      and controls showed similar twofold increases over baseline after secretin
      administration. When normal glucose tolerant and type 2 diabetic patients were
      pooled and compared against type 1 diabetes mellitus, the differences were
      statistically significant (p < 0.03). Total amylase response correlated
      positively, but weakly, with 24 h urinary C-peptide excretion (r = 0.507; p <
      0.112), but not with glycemic control, duration of diabetes, or indices of
      autonomic neuropathy. CONCLUSIONS: Patients with type 1 diabetes mellitus, but
      not type 2 diabetes mellitus, have reduced pancreatic exocrine function,
      supporting the concept of a local paracrine effect of insulin on pancreatic
      acinar cells. Further studies are needed to determine the clinical impact of this
      deficiency, and whether such patients with type 1 diabetes mellitus would benefit
      from therapy with pancreatic enzyme supplementation.

PMID- 15971158
TI  - Early carotid atherosclerosis in overweight non-diabetic individuals is
      associated with subclinical chronic inflammation independent of underlying
      insulin resistance.
AB  - Overweight in children and young adults is an increasing problem in Western
      industrialized countries with potential impact on cardiovascular morbidity.
      Whether early arterial wall thickening in these subjects mainly results from the
      often associated insulin resistance syndrome or from increased subclinical
      chronic inflammation probably triggered by adipose tissue is still under
      discussion. We therefore determined insulin sensitivity index (ISI) by performing
      an euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate 1
      mU/kg/min) and high-sensitivity C-reactive protein (hsCRP) levels in relation to
      the intima-media thickness (IMT) at the common carotid artery (high resolution
      ultrasound; 13 MHz) in 81 young (age 33 +/- 1 years), moderately overweight
      subjects. To reduce the number of confounding variables, subjects with
      disturbances in glucose metabolism (75 g oral glucose tolerance test) and
      hypertension were excluded. As expected, higher BMI was positively correlated
      with increased IMT (r = 0.358; p = 0.001). After multiple regression analysis,
      hsCRP levels independently correlated to IMT (r = 0.251; p = 0.03), even after
      adjusting for age, sex, BMI, ISI, LDL cholesterol and smoking as cofactors.
      However, taking all above listed factors into account, glucose-clamp assessed
      insulin sensitivity was not correlated with IMT. Thus, overweight might trigger
      inflammatory mechanisms leading to vascular wall hypertrophy independent of the
      insulin resistance syndrome already early in life.

PMID- 15971159
TI  - Reproducibility of an oral fat tolerance test is influenced by phase of menstrual
      cycle.
AB  - Knowledge of the reproducibility of oral fat tolerance tests is important for
      experimental design and data interpretation. In this study, seven normolipidaemic
      men underwent two fat tolerance tests (blood taken fasting and for six hours
      after a meal containing 1.2 g fat, 1.2 g carbohydrate per kg body mass) with an
      interval of one week. Eleven normolipidaemic women underwent two fat tolerance
      tests--one during the follicular phase of the menstrual cycle, the other during
      the mid-luteal phase. Dietary intake was controlled for two days and subjects
      refrained from exercise for three days before each test. There was no significant
      difference in postprandial triglyceride responses between the two tests in the
      men (10.20 +/- 3.45 mmol/l.h vs. 9.68 +/- 2.77 mmol/l.h, NS) (mean +/- SD);
      intraclass correlation coefficient between the two tests was 0.93, and within
      subject coefficient of variation was 10.1 %. In the women, the postprandial
      triglyceride response was lower in the luteal phase (6.75 +/- 1.83 mmol/l.h) than
      in the follicular phase (8.36 +/- 3.71 mmol/l.h) (p = 0.05), intraclass
      correlation was 0.65 and within-subject coefficient of variation was 23.2 %.
      These results suggest that, with adequate control of preceding lifestyle,
      reproducibility of postprandial triglyceride responses is high in men, but
      menstrual phase should be taken into consideration when studying these responses
      in women.

PMID- 15971160
TI  - Iatrogenic arteriovenous fistula after revascularization of the hand.
AB  - This is the first report of an iatrogenic arteriovenous fistula complicating
      revascularization of an incomplete amputation of the hand, due to inadvertent
      anastomosis of the proximal radial artery to the distal cephalic vein. This
      resulted in a severely painful, massively swollen hand, which was initially
      diagnosed as an infection or poor venous outflow and eventually required a below
      elbow amputation. This complication of replantation or revascularization should
      be preventable by carefully matching the thickness of the vessel wall and the
      diameter of the lumen, to avoid anastomosing a proximal artery to a distal vein.

PMID- 15971161
TI  - Arthroplasty of the elbow joint using vascularized iliac bone graft for
      reconstruction of massive bone defect of the distal humerus.
AB  - The authors present a case of a 39-year-old man with an enormous bone defect of
      the distal humerus secondary to an infected nonunion, who was successfully
      reconstructed using a vascularized iliac bone graft. The use of a vascularized
      iliac bone graft may be an option for reconstructing such massive defects of the
      metaphyseal area of the humerus.

PMID- 15971162
TI  - A rare and serious complication of the radial forearm flap donor site:
      osteomyelitis of the radius.
AB  - Although the radial forearm flap has become a workhorse for the reconstructive
      surgeon, it has some known disadvantages, especially relating to donor area
      complications. The authors present a serious but rare complication of the radial
      forearm donor site. Osteomyelitis of the radius at the flap donor site was
      observed in a 48-year-old man 5 weeks after flap surgery. Although the flap was
      raised fasciocutaneously without a bony portion, infection of the radius was
      determined. The infection was successfully treated with surgical debridement and
      simultaneous administration of a proper antibiotic regimen. One should keep in
      mind that osteomyelitis of the radius may be encountered as one of the serious
      donor site complications of the radial forearm flap that may have detrimental
      effects on hand functions.

PMID- 15971163
TI  - Hypothenar flap based on a cutaneous perforator branch of the ulnar artery: an
      anatomic study.
AB  - This study describes a constant cutaneous perforator branch of the ulnar artery
      of the hand and a hypothenar arterial flap based on it. Eighteen amputated hands
      of 10 fresh cadavers were used for the study. Red latex was injected into the
      axillary arteries of nine specimens and radiopaque lead oxide-gelatin mixture
      into the remaining nine. Then, the cutaneous perforator branch of the ulnar
      artery was identified by marginal dissection and radiographed. The cutaneous
      perforator branch was found constantly in all 18 specimens and was named the
      "hypothenar perforator" (HP). On radiograph, a coordinate was set up with an
      origin (pisiform), a transverse x (through the pisiform and hamate of the carpal
      bones), and a proximal to distal y (through the pisiform and 4th interdigital
      web) axes. The HP was situated at 10.1 +/- 3.6 mm lateral to the pisiform (on the
      x axis) and 20.0 +/- 7.0 mm distal (on the y axis). A hypothenar flap based on
      the HP is suitable for covering small defects of the fingers, and the donor site
      can be closed primarily.

PMID- 15971164
TI  - Palmar arch revascularization for arterial occlusion of the distal upper
      extremity.
AB  - During a period of nine years, 10 patients, ages 42 to 66 years (55 +/- 7, mean
      +/- SD) underwent upper extremity bypass for ischemic changes to the hand not
      responsive to conservative management. Patients were referred from the vascular
      department at the authors' institution. Preoperative angiograms were performed
      and attempts at angioplasty or intravenous attempts to dissolve clots were
      carried out (with tissue plasminogen activator-tPA) when appropriate. Patients
      with persistent upper extremity ischemia and an obvious occlusion with
      reconstitution in the hand were candidates for upper extremity bypass to the
      palmar arch. All patients had upper extremity bypasses performed with reverse
      saphenous vein grafts. The proximal anastomoses (end-to-side) were performed by
      either the vascular or plastic surgery team, while all distal anastomoses (end-to
      side) were performed by plastic surgery team microscopic magnification to the
      deep or superficial palmar arch. Postoperative follow-up ranged from 3 months to
      3 years. The bypass graft to the hand resulted in improved pain and resolution of
      tissue ischemia in all cases. Patients with preoperative ulcers were completely
      healed by 3 months. The results are in accordance with previous studies
      demonstrating that improved blood flow afforded by the procedure can improve the
      healing of recalcitrant ulcers and mitigate the symptoms of ischemic changes. In
      addition, end-to-side anastomosis to the palmar arch offers significant
      advantages, in that the continuity of the arch is maintained with all possible
      outflow vessels, and the problems associated with size discrepancy in the
      anastomosed vessels are eliminated.

PMID- 15971165
TI  - Detrimental effects of immobilization on functional recovery after sciatic nerve
      crush.
AB  - Peripheral-nerve trauma has been a challenge to surgeons, with significant
      advances in the surgery of repair. Immobilization of the injured limb after
      repair has been the traditional method of treatment. Although peripheral-nerve
      regeneration has been studied extensively, the correlation between functional
      recovery and the immobilization period has not been well-documented. In the
      present study, the authors studied the effects of immobilization on axonal
      regeneration after sciatic crush injury. They found a detrimental effect of
      immobilization on the functional recovery.

PMID- 15971166
TI  - Effects of 360-degree pedicle torsion on island skin flaps: experimental study in
      rats.
AB  - This study was carried out to observe the isolated effects of pedicle torsion on
      island skin flaps, without further damaging the pedicle. Twelve adult male
      Sprague-Dawley rats, weighting 240 to 300 gr, were used, and hexagonal flaps with
      edges measuring 1.5 cm and pedicles measuring 1 cm in length were raised in the
      inguinal region. The animals were divided into two groups. In Group A, flaps were
      re-sutured to the donor beds without any rotation. In Group B, flaps were rotated
      360 degrees, applying the same degree of torsion to their pedicles before re
      suturing. After 7 days, the percentage of surviving skin areas of the flaps was
      determined by planimetry, and transverse sections of the flaps and pedicles were
      taken and evaluated in terms of signs of arterial or venous insufficiency.
      Statistically significant differences between the groups were determined by
      analyses using the multiple comparisons test. Pedicle torsion in Group B did not
      affect flap viability, both macroscopically and microscopically. The presented
      study shows that 360-degree torsion applied to the pedicle of the flap in this
      model had no effect on flap viability.

PMID- 15971167
TI  - Association of vascular injury with the proximal side branch and assessment of
      thrombosis rates in a new microarterial traction model.
AB  - The higher rate of anastomotic failure in avulsion injuries has been attributed
      mostly to the uncertainty in determining the uninjured vessel segment suitable
      for anastomosis and resection past a proximal branch that has been proposed to
      achieve good arterial flow. A graded, longitudinal, microarterial traction model
      in rats has been used to examine the histopathologic aspects of the extent of
      vascular injury and its association with the proximal side branch. Additionally,
      anastomoses were performed following traction, and thromboses rates were
      determined. Results indicated a more proximal vessel injury with increasing rates
      of traction and, although the vessel segment proximal to the side branch was
      spared, up to a certain degree of traction, the injury extended beyond this point
      with more aggressive traction force. Consistently increasing rates of thromboses,
      significantly higher than the control group, were demonstrated. This model may be
      of use in further studies on the efficacy of various antithrombotic agents.

PMID- 15971170
TI  - Plasmalemmal vesicle-associated protein (PLVAP) is expressed by tumour
      endothelium and is upregulated by vascular endothelial growth factor-A (VEGF).
AB  - Vascular endothelial growth factor-A (VEGF) is an important regulator of vascular
      permeability. In preclinical studies, VEGF induces endothelial fenestrations in
      pre-existing and neo-vasculature, while inhibition of VEGF leads to a reduction
      in endothelial fenestrations. Recently, vascular regression in response to VEGF
      inhibition has been shown to correlate with the presence of endothelial
      fenestrations. Plasmalemmal vesicle-associated protein (PLVAP) is believed to be
      a component of diaphragmed endothelial fenestrations, but a direct relationship
      with VEGF signalling has not been established. The aim of this study was to
      characterize the expression pattern of PLVAP and investigate whether PLVAP is a
      transcriptional target of VEGF signal transduction. The expression pattern of
      PLVAP was characterized in normal and neoplastic human tissues by in situ
      hybridization and/or immunohistochemistry. The role of VEGF signal transduction
      in the regulation of PLVAP expression was investigated in vitro using receptor
      selective engineered forms of VEGF, a neutralizing monoclonal antibody against
      VEGF, and inhibitors of downstream signalling pathways. PLVAP mRNA and protein
      were widely expressed in the endothelium of normal and neoplastic tissues. In
      cultured endothelial cells, VEGF signalling through receptor 2 stimulated
      expression of PLVAP total RNA and protein. This induction could be blocked with
      an anti-VEGF monoclonal antibody and by inhibitors of phosphatidylinositol 3
      kinase (LY294002) or p38 mitogen-activated protein kinase (SB203580), but not by
      PD98059, a mitogen-activated protein/extracellular signal-regulated kinase 1
      inhibitor. These data show that PLVAP is more widely expressed in the vasculature
      of normal tissues than previously thought and that it is expressed in the
      vasculature of most human tumours. We suggest that PLVAP is a downstream target
      of VEGF signalling. This work solidifies the association between VEGF and the
      appearance and maintenance of fenestrations by providing a potential mechanistic
      link.

PMID- 15971171
TI  - Comparison of 15 different stents in superficial femoral arteries by high
      resolution MRI ex vivo and in vivo.
AB  - PURPOSE: To evaluate the MRI compatibility of 15 different commercially
      available, new generation, U.S. Food and Drug Administration (FDA)-approved
      stents suitable for deployment in superficial femoral arteries (SFAs), and to
      identify the ones that permit MRI to visualize the wall and lumen of stented
      arteries with sufficient spatial and contrast resolution to quantify restenosis
      after stent placement. MATERIALS AND METHODS: A total of 13 nitinol stents and
      two stainless-steel stents were placed in excised cadaveric SFAs and imaged by
      MRI at 1.5 T ex vivo. The images were evaluated qualitatively for the presence of
      artifacts and for the effects of the stent on image contrast, and quantitatively
      for the effect on signal-to-noise ratio (SNR) of the lumen of the artery inside
      the stent compared to the SNR of the fluid outside the artery. A nitinol stent
      was placed in the SFA of a 60-year-old man and imaged at 1.5 T in vivo. RESULTS:
      Both the vessel wall and the lumen could be visualized in cadaveric SFAs
      containing either the Absolute nitinol stent, the Dynalink nitinol stent, or the
      aSpire nitinol-covered stent. Their inside stent/outside stent SNR was 0.7, 0.8,
      and 0.8, respectively. The other 10 nitinol stents tested obscured the lumen but
      did not cause major image shape artifacts. Both stainless-steel stents tested,
      the WallGraft and WallStent, completely obscured the lumen and caused significant
      distortion of the image shapes. When the Dynalink stent was inserted into a
      highly stenosed SFA in vivo, the image showed a dark expanded eccentric lumen,
      circumscribed by a medium intensity band containing the stent. CONCLUSION: MRI
      can be used to visualize both the lumen and wall of SFAs containing selected
      nitinol stents ex vivo and in vivo. These results suggest that MRI can be used to
      monitor restenosis in stents placed in the femoral arterial bed.

PMID- 15971172
TI  - Comparison of 0.5-M Gd-DTPA with 1.0-M gadobutrol for magnetic resonance
      angiography of the supplying arteries of the spinal cord in thoracoabdominal
      aortic aneurysm patients.
AB  - PURPOSE: To prospectively compare 0.5-M gadopentetate dimeglumine (Gd-DTPA) with
      1.0-M gadobutrol for contrast-enhanced magnetic resonance angiography (CE-MRA) of
      the blood supplying arteries of the spinal cord in patients referred for open
      surgical repair of a thoracoabdominal aortic aneurysm (TAAA). MATERIALS AND
      METHODS: A total of 11 patients with a TAAA underwent two three-dimensional CE
      MRA exams of the aorta, segmental arteries (SAs), artery of Adamkiewicz (AKA),
      and anterior spinal artery (ASA). Imaging was performed on two separate occasions
      using Gd-DTPA and gadobutrol as contrast agents at 0.3 mmol/kg. Images were
      evaluated by measuring signal-to-noise (SNR) and contrast-to-noise (CNR) ratios
      and were judged for different image quality criteria by two blinded observers.
      RESULTS: In all patients both CE-MRA exams were of sufficient image quality to
      detect the AKA and ASA. No significant differences in SNR and CNR were observed
      between the two contrast agents. According to the observers, no significant
      differences in subjective image quality were found. CONCLUSIONS: Using both
      contrast agents it was possible to visualize the ultrasmall spinal cord arteries
      in all cases. The use of the 1.0-M contrast agent did not improve image quality
      of CE-MRA images of the blood supplying arteries of the spinal cord compared to
      the 0.5-M contrast agent.

PMID- 15971173
TI  - Repeatability of a novel technique for in vivo measurement of three-dimensional
      patellar tracking using magnetic resonance imaging.
AB  - PURPOSE: To determine the repeatability of a novel noninvasive MRI-based
      technique for measuring patellofemoral kinematics in vivo. MATERIALS AND METHODS:
      The patellar kinematics measurement method relies on registering bone models
      (with associated coordinate systems) developed from a high resolution MRI scan to
      loaded bone positions derived from fast, low resolution MRI scans. The
      intrasubject variability, high resolution to low resolution registration error,
      and interexperimenter repeatability were quantified in experiments on three
      healthy subjects. RESULTS: The intrasubject variability and registration error
      were within range of the accuracy of our procedure; specifically, less than or
      equal to 1.40 degrees for orientation and 0.81 mm for translation. The
      interexperimenter repeatability was less than or equal to 1.28 degrees for
      orientation, with the exception of patellar spin, and 0.68 mm for translation.
      CONCLUSION: Our novel measurement technique can measure three-dimensional
      patellar tracking noninvasively during loaded flexion in a repeatable manner. Our
      results compare well to another noninvasive tracking protocol, fast phase
      contrast MRI, which has a reported subject interexam variability of 2.4 degrees
      or less for patellar orientation. A particular strength of our method is that
      axes and high-resolution bone models need only be determined once for
      intrasubject comparisons. The method is sufficiently accurate and repeatable to
      detect clinically significant changes in patellofemoral kinematics.

PMID- 15971174
TI  - Routine clinical brain MRI sequences for use at 3.0 Tesla.
AB  - PURPOSE: To establish image parameters for some routine clinical brain MRI pulse
      sequences at 3.0 T with the goal of maintaining, as much as possible, the well
      characterized 1.5-T image contrast characteristics for daily clinical diagnosis,
      while benefiting from the increased signal to noise at higher field. MATERIALS
      AND METHODS: A total of 10 healthy subjects were scanned on 1.5-T and 3.0-T
      systems for T(1) and T(2) relaxation time measurements of major gray and white
      matter structures. The relaxation times were subsequently used to determine 3.0-T
      acquisition parameters for spin-echo (SE), T(1)-weighted, fast spin echo (FSE) or
      turbo spin echo (TSE), T(2)-weighted, and fluid-attenuated inversion recovery
      (FLAIR) pulse sequences that give image characteristics comparable to 1.5 T, to
      facilitate routine clinical diagnostics. Application of the routine clinical
      sequences was performed in 10 subjects, five normal subjects and five patients
      with various pathologies. RESULTS: T(1) and T(2) relaxation times were,
      respectively, 14% to 30% longer and 12% to 19% shorter at 3.0 T when compared to
      the values at 1.5 T, depending on the region evaluated. When using appropriate
      parameters, routine clinical images acquired at 3.0 T showed similar image
      characteristics to those obtained at 1.5 T, but with higher signal-to-noise ratio
      (SNR) and contrast-to-noise ratio (CNR), which can be used to reduce the number
      of averages and scan times. Recommended imaging parameters for these sequences
      are provided. CONCLUSION: When parameters are adjusted for changes in relaxation
      rates, routine clinical scans at 3.0 T can provide similar image appearance as
      1.5 T, but with superior image quality and/or increased speed.

PMID- 15971175
TI  - Evolution of lesion volume in acute stroke treated by intravenous t-PA.
AB  - PURPOSE: To determine the evolution of the ischemic lesion volumes in a
      population treated with tissue plasminogen activator (t-PA), MRIs were performed
      before treatment and 24 hours later; final infarct size was evaluated 60 days
      later. MATERIALS AND METHODS: A total of 42 patients with hemispheric stroke were
      recruited for a thrombolytic study. Intravenous t-PA was given after MRI within
      the first seven hours after stroke onset. Volumes were evaluated on day 0 and day
      1 with diffusion-weighted imaging (DWI), on day 60 with T2-weighted imaging
      (T2WI), and recanalization was assessed based on day 1 MR angiography (MRA).
      RESULTS: Lesion volume increased between day 0 and day 1, and decreased between
      day 1 and day 60. It was lower in the group of patients with recanalization on
      day 1 MRA. CONCLUSION: Volume analysis emphasizes the effectiveness of
      recanalization as a predictive factor for better outcome, based on final infarct
      size. The decrease in lesion volumes between day 1 and day 60 suggests that other
      factors leads to overestimation of day 1 abnormal diffusion volume. This could
      explain the delayed partial reversibility of the DWI abnormality.

PMID- 15971176
TI  - A comparison of noninvasive MRI-based methods of estimating pulmonary artery
      pressure in pulmonary hypertension.
AB  - PURPOSE: To assess the accuracy of several noninvasive MRI-based estimators of
      pulmonary artery pressure by comparing them with invasive pressure measurement.
      MATERIALS AND METHODS: We compared five MRI methods with invasive pressure
      measurement by catheterization, in one group of pulmonary hypertension (PH)
      patients. Doppler echocardiography was included as a reference method. Main
      inclusion criterion was a mean pulmonary artery pressure above 25 mmHg at
      catheterization. MRI velocity quantification was used to obtain pulmonary flow
      acceleration and ejection times, and pulse wave velocity. The ventricular mass
      index was also assessed on MRI. Two commercially available 1.5-T systems were
      used for this study. RESULTS: Data from 44 patients were analyzed. Correlation of
      acceleration time with mean pressure was: r = -0.21, P = 0.21, correlation of the
      acceleration/ejection time ratio with systolic pressure was: r = -0.26, P = 0.01.
      The ventricular mass index showed the best correlation with mean pressure, with r
      = 0.56, P < 0.001. Using the pulse wave velocity and the cross-sectional area of
      the pulmonary artery, the mean pressure could not be estimated accurately.
      CONCLUSION: Accurate estimation of pulmonary artery pressure in PH patients was
      not feasible by the MRI estimators studied. These noninvasive methods cannot
      replace right heart catheterization at this moment.

PMID- 15971177
TI  - Dynamic contrast-enhanced MRI for assessing the disease activity of multiple
      myeloma: a comparative study with histology and clinical markers.
AB  - PURPOSE: To examine whether parameters of dynamic, contrast-enhanced MRI (DCE
      MRI) reflect the degree of infiltration and vessel density in corresponding bone
      marrow biopsy specimens. MATERIALS AND METHODS: The pelvis of 24 patients with
      multiple myeloma (MM) was examined using contrast-enhanced DCE MRI. Biopsy was
      obtained from the spina iliaca posterior superior. Using a two-compartment model
      (assuming one intravascular and one interstitial compartment), the parameters
      amplitude (A, the maximum, relative signal increase over baseline) and the
      exchange rate constant (k(ep), describing the redistribution of contrast agent
      from the interstitial into the intravascular compartment) in the biopsied region
      were calculated and compared with the histological and clinical data. RESULTS:
      DCE MRI parameters were significantly higher in lesions with marked infiltration
      than with mild or no infiltration (P < 0.05). The amplitude normalized to that in
      the iliac artery (A(n)), but not k(ep), was higher in lesions with high vessel
      density at histology (P = 0.01). Higher k(ep) levels were found in presence of
      increased serum immunoglobulins. CONCLUSION: Increased contrast uptake in the
      bone marrow of MM patients indicates at least moderate tumor involvement.
      Furthermore, the contrast enhancement correlates with vessel-density and serum
      markers of disease activity.

PMID- 15971178
TI  - Importance of bone-conducted sound transmission on patient hearing in the MR
      scanner.
AB  - PURPOSE: to evaluate the influence of bone-conduction in the MR environment
      compared to a standardized acoustic environment. MATERIALS AND METHODS: Acoustic
      noise is an unwanted side effect of MRI that is commonly tackled with passive
      hearing protection. In an MR scanner, however, with the patient completely
      surrounded by the MR sounds and in close contact with the vibrating MR table and
      gantry, bone-conduction may increase subjective sound levels, restricting the
      efficacy of passive protection that reduces air-conducted noise only. A total of
      10 volunteers were subjected to pure MR tones, covering the frequency range
      relevant for hearing and at 60 dB, generated through the MR system's gradient
      coils. Bone-conduction was determined for various passive damping conditions in
      an MR scanner and was compared to that acquired in an acoustically-calibrated
      environment. The contribution of mechanical vibrations to bone-conduction was
      determined. Also, with a microphone in the ear canal, the objective efficacy of
      the passive protection was measured. RESULTS: We found no difference between the
      bone-conduction experiments executed inside the imager and in the acoustically
      controlled environment. The overall insertion loss of the passive hearing
      protectors was over 20 dB with strongest effects at 0.4 and 2.5 kHz. CONCLUSION:
      As bone-conduction is not more pronounced inside the MR scanner than outside, the
      previous reports on the subjective evaluation of protection devices in MRI hold
      their validity.

PMID- 15971179
TI  - MRI in Crohn's disease.
AB  - Technological developments have extended the role of MRI in the evaluation of the
      gastrointestinal tract. The potential of MRI to evaluate disease activity in
      Crohn's disease has been investigated extensively, as MRI has intrinsic
      advantages over other techniques, including noninvasiveness and the absence of
      ionizing radiation. For perianal fistulizing disease MRI has become a mainstay in
      evaluation of disease, as localization and extent of disease can be very well
      appreciated using both T2-weighted and T1-weighted sequences, fat suppression,
      and intravenous contrast medium. Imaging of the small bowel and colon in Crohn's
      disease is more complicated due to bowel peristalsis and respiratory movement.
      However, using fast breathhold sequences and intravenous spasmolytic medication,
      images of good diagnostic quality can be acquired. To obtain sufficiently
      distended bowel, which in our estimation is a prerequisite for evaluation of the
      bowel, MR enteroclysis can be performed. However, applicability of different oral
      contrast media has been studied, as a noninvasive method for bowel distension
      would be preferable. Abdominal MRI is a valuable imaging technique for evaluation
      of luminal, transmural, and extraintestinal manifestations of Crohn's disease as
      degree of disease activity, presence of luminal pathology (e.g., stenoses), and
      extraintestinal manifestations of disease (e.g., abscesses, fistulas) can be
      accurately assessed.

PMID- 15971180
TI  - Single-breathhold, four-dimensional, quantitative assessment of LV and RV
      function using triggered, real-time, steady-state free precession MRI in heart
      failure patients.
AB  - PURPOSE: To validate a novel, real-time, steady-state free precession (SSFP),
      single-breathhold technique for the assessment of left ventricular (LV) and right
      ventricular (RV) function in heart failure patients. MATERIALS AND METHODS: A
      total of 20 heart failure patients (mean age 59 +/- 17 years) underwent scanning
      with our new, real-time, spiral SSFP sequence in which each cardiac phase was
      acquired in 118 msec at a resolution of 1.8 x 1.8 mm. Each cardiac slice (1-cm
      thick) was automatically advanced based on a cardiac trigger, allowing complete
      coverage of the heart in a single breathhold. The patients also underwent LV and
      RV assessment with the gold standard: multiple breathhold, cardiac-gated,
      segmented k-space strategy. LV and RV end-systolic volume (ESV) and end-diastolic
      volume (EDV) and LV mass were compared between the two imaging techniques.
      RESULTS: The new real-time strategy was highly concordant with the gold standard
      technique in the assessment of LVEDV (r = 0.98), LVESV (r = 0.98), RVESV (r =
      0.86), RVEDV (r = 0.91), LVMASS (r = 0.95), RVEF (r = 0.70), and LVEF (r = 0.94).
      The mean bias (95% confidence interval [CI]) for each parameter is LVEDV: 10.6 cc
      (cm(3)) (3.8-17.4 cc), LVESV: -0.8 cc (-5.3 to 3.7 cc), RVEDV: 3.7 cc (-5.6 to
      13.2 cc), RVESV: -3.1 cc (-11.1 to 4.9 cc), LVMASS: 26 g (12.4-39.8 g), RVEF: 
      2.9% (1.3 to -7.2 %), LVEF: 1.9% (5 to -1.1%). In addition, data acquisition was
      only nine +/- two seconds with the real-time strategy vs. 312 +/- 41 seconds for
      the standard technique. CONCLUSION: In patients with heart failure, real-time,
      spiral SSFP allows rapid and accurate assessment of RV and LV function in a
      single-breath hold. Using the same strategy, increased temporal resolution will
      allow real-time assessment of cardiac wall motion during stress studies.

PMID- 15971181
TI  - Correction of phase offset errors in main pulmonary artery flow quantification.
AB  - PURPOSE: To investigate whether an existing method for correction of phase offset
      errors in phase-contrast velocity quantification is applicable for assessment of
      main pulmonary artery flow with an MR scanner equipped with a high-power gradient
      system. MATERIALS AND METHODS: The correction method consists of fitting a
      surface through the time average of stationary pixels of velocity-encoded phase
      images, and subtracting this surface from the velocity images. Pixels are
      regarded as stationary if their time standard deviation falls into the lowest
      percentile. Flow was measured in the main pulmonary artery of 15 subjects. Each
      measurement was repeated on a stationary phantom. The phase offset error in the
      phantom was used as a reference. Correction was applied with varying polynomial
      surface orders (0-5) and stationarity percentiles (5-50%). The optimal surface
      order and stationarity percentile were determined by comparing the fitted surface
      with the phantom. RESULTS: Using a first-order surface and a (noncritical) 25%
      percentile, the correction method significantly reduced the phase offset error
      from 1.1 to 0.35 cm/second (RMS), which is equivalent to a reduction from 11% to
      3.3% of mean volume flow. Phase error correction strongly affected stroke volume
      (range -11 to 26%). CONCLUSION: The method significantly reduces phase offset
      errors in pulmonary artery flow.

PMID- 15971182
TI  - Peritumoral fat-spared area is well correlated with the presence of temporal
      peritumoral enhancement in hepatic hemangioma in fatty liver.
AB  - PURPOSE: To assess the relationship between temporal peritumoral enhancement and
      peritumoral focal fat sparing adjacent to hepatic hemangiomas. MATERIALS AND
      METHODS: On the basis of MRI and sonographic imaging follow-up, 51 hepatic
      hemangiomas were identified in 37 patients, who had both hepatic hemangiomas and
      focal fat-sparing areas in fatty liver. Among them, 36 tumors were associated
      with peritumoral focal fat spares. The association between the temporal
      peritumoral enhancement in the early arterial phase of dynamic MRI and
      peritumoral fat sparing in the same hemangioma was investigated. Furthermore, the
      configuration of the temporal peritumoral enhancement was correlated with that of
      the peritumoral focal fat-sparing area. We used Chi square and Fisher's exact
      test for statistic analysis. RESULTS: A total of 31 out of 36 hemangiomas (86.1%)
      showed both peritumoral focal fat spares and temporal peritumoral enhancement.
      The presence of temporal peritumoral enhancement is significantly related to that
      of peritumoral focal fat-sparing (P < 0.001). A total of 21 of the 31 tumors
      (67.7%) presented with similar configuration of the peritumoral focal fat-sparing
      area and temporal peritumoral enhancement area with respect to size and shape.
      The remaining 10 hemangiomas showed similar shape but slightly different size in
      these two imaging characteristics. CONCLUSION: Temporal peritumoral enhancement
      seen in hepatic hemangioma might be related to focal fatty sparing adjacent to
      the hemangiomas.

PMID- 15971183
TI  - Local staging of rectal carcinoma and assessment of the circumferential resection
      margin with high-resolution MRI using an integrated parallel acquisition
      technique.
AB  - PURPOSE: To assess the diagnostic accuracy of integrated parallel acquisition
      technique (iPAT) in local staging of rectal carcinoma in comparison to
      conventional high-resolution MRI. MATERIALS AND METHODS: A total of 28 patients
      with a neoplasm of the rectum and 15 control patients underwent MRI of the
      pelvis. High-resolution images were acquired conventionally and with iPAT using a
      modified sensitivity encoding (mSENSE). Image quality, signal-to-noise and
      contrast-to-noise ratios (SNR, CNR), tumor extent, nodal status, and delineation
      of the circumferential resection margin (CRM) were compared. In 19 patients with
      a carcinoma, MR findings were correlated with the histopathological diagnosis.
      Tumor distance to the CRM was matched with resection specimen in 12 cases.
      RESULTS: The comparison of both MR techniques revealed no clinically relevant
      differences in tumor staging and delineation of the CRM, though SNR and CNR were
      significantly lower in mSENSE images. Tumor stage was concordant in 17 of 19
      cases compared to histopathology. In four of nine patients with T3 and T4
      carcinomas, the histopathological resection margin was < or =2 mm, in five cases
      MRI predicted a margin of < or =2 mm. CONCLUSION: The application of iPAT in
      local staging of rectal carcinoma is time-saving and does not degrade diagnostic
      accuracy. Tumor stage, nodal status, and the CRM can be assessed equally compared
      to conventional acquisition techniques.

PMID- 15971184
TI  - (1)H MRI of pneumococcal pneumonia in a murine model.
AB  - PURPOSE: To detect and quantify pulmonary lesions due to pneumococcal pneumonia
      in a murine model by (1)H MRI. MATERIALS AND METHODS: Pneumonia was induced in
      mice (N = 5) by intranasal administration of about 1 x 10(6) colony-forming units
      (CFU) of Streptococcus pneumonie. A group of noninfected animals (N = 5) was used
      as a control group. MRI was performed, 48 hours after infection induction, at 4.7
      T. ECG-gated gradient-echo (GRE) sequences with TE = 5 msec were used. After MRI
      examination, the animals were sacrificed for histological examination. RESULTS:
      Lungs appeared at MRI as regions with signal intensity (SI) at the level of the
      noise. Lesions appeared as hyperintense regions over the background and were
      localized mainly in the apical part of the lungs, in the medial and peribronchial
      regions. The anatomical localization of the lesions was confirmed by histology.
      The total lesion volume quantified by MRI data correlated with the total lesion
      volume quantified by histology. CONCLUSION: This work shows that standard (1)H
      MRI allows detection and quantification of lesions due to pneumococcal pneumonia
      in mice.

PMID- 15971185
TI  - Fast and high-resolution MR sialography using a small surface coil.
AB  - PURPOSE: To establish a fast and high-resolution MR sialographic technique that
      provides fast and high-resolution imaging. MATERIALS AND METHODS: MR sialography
      was performed on a 1.5-T MR imager using a small (47-mm) surface coil. We
      determined appropriate sequence parameters, and then applied the technique to the
      salivary glands of 143 patients with xerostomia (including those with Sjogren's
      syndrome or hyperlipidemia) or salivary gland inflammation. We compared the high
      resolution MR sialography with conventional x-ray sialography in the patients
      with xerostomia to evaluate the effectiveness of the MR sialography technique.
      RESULTS: We found that a single-shot, single-slice MR sialography (TR/TR/number
      of signal acquisitions [NSA] = 8000 msec/1000 msec/6) using a small surface coil
      provides excellent duct images that are clinically feasible with fast (imaging
      time of 56 seconds) and high-resolution images. An alternative three-dimensional
      MR sialography technique provided better details of the branches at the expense
      of imaging time. The MR sialography technique using a small surface coil depicted
      effectively the ductal changes in the salivary glands in patients with or without
      Sjogren's syndrome, reflecting the severity of the diseases. CONCLUSION: We
      conclude that MR sialography can be performed using a fast and high-resolution
      sequence.

PMID- 15971186
TI  - Apparent diffusion coefficient and fractional anisotropy in spinal cord: age and
      cervical spondylosis-related changes.
AB  - PURPOSE: To present the apparent diffusion coefficient (ADC) and fractional
      anisotropy (FA) change with age in the normal spinal cord and in cervical
      spondylosis. MATERIALS AND METHODS: A total of 11 normal volunteers and 79
      cervical spondylosis patients entered this study. Line scan diffusion tensor
      images were obtained in a 1.5-Tesla whole-body scanner using a phased-array spine
      coil. The ADC and FA values were measured on a sagittal section. Spearman
      correlation of ADC/FA vs. age for normal spinal cord was calculated. RESULTS: The
      mean ADC of the normal spinal cord was 0.81 +/- 0.03 microm(2)/msec at the
      relatively wide C2-C3 level and 0.75 +/- 0.06 microm(2)/msec at the more narrow
      C4-C7 level. The FA at the corresponding level was 0.70 +/- 0.05 and 0.66 +/-
      0.03, respectively. With age, ADC showed positive correlation (Spearman, r =
      0.242) and FA exhibited negative correlation (Spearman, r = -0.244). A total of
      54% of all spondylosis cases showed elevated ADC (P < 0.001) and decreased FA (P
      < 0.001) at the stenotic spinal canal level compared with the normal spinal cord.
      The average ADC and FA of high-signal lesions on T2-weighted images (seven
      patients) were 1.28 +/- 0.33 microm(2)/msec and 0.46 +/- 0.12, respectively.
      CONCLUSION: ADC increases and FA decreases with age in the normal spinal cord.
      Elevated ADC and reduced FA were measured in the spinal cord of spondylosis cases
      with clinical symptoms of myelopathy.

PMID- 15971187
TI  - Myocardial first-pass perfusion assessment using rotational long-axis MRI.
AB  - PURPOSE: To study a first-pass myocardial perfusion imaging method, such that
      long-axis imaging slices are obtained rotationally around the short-axis centroid
      of the left ventricular cavity, in order to improve myocardial coverage and
      better delineate the basal and apical myocardium. MATERIALS AND METHODS: This
      rotational long-axis (RLA) method was examined in 12 volunteers and compared to
      the perfusion images from conventional parallel short-axis (PSA) acquisitions in
      terms of the contrast to noise ratio (CNR), relative signal upslope and
      myocardial coverage. Both RLA and PSA first-pass perfusion images were acquired
      on each volunteer with otherwise identical imaging parameters using the partial
      Fourier saturation recovery steady state gradient echo sequence with refocused
      magnetization (TrueFISP) technique. RESULTS: Compared to PSA, RLA perfusion
      images with identical imaging parameters on the same subject exhibit an average
      of near 30% improvement in total myocardial area imaged. In addition, true basal
      and apical myocardium was seen on RLA, but not on PSA. The mean CNR and relative
      upslope were similar between the two techniques. CONCLUSIONS: This RLA perfusion
      imaging scheme is superior to the conventional PSA approach in terms of extent
      myocardial coverage and delineation of basal and apical regions of the left
      ventricle.

PMID- 15971188
TI  - Apparent diffusion coefficient measurements with diffusion-weighted magnetic
      resonance imaging for evaluation of hepatic fibrosis.
AB  - PURPOSE: To evaluate the use of apparent diffusion coefficient (ADC) measurements
      based on diffusion-weighted MRI (DWI) to assess stage of liver disease. MATERIALS
      AND METHODS: A total of 31 patients who underwent both a liver biopsy and DWI and
      132 patients who only underwent DWI were enrolled. Biopsy specimens were scored
      for fibrosis and necroinflammation according to the Knodell histology activity
      index (HAI). The 31 patients consisted of 21 patients with chronic hepatitis and
      10 with cirrhosis (Child-Pugh stage A in nine and stage B in one), and the 132
      patients consisted of 56 patients with cirrhosis (Child-Pugh stage A in 41, stage
      B in 10, and stage C in five), 42 with chronic hepatitis, and 34 with normal
      liver function. The ADCs in the liver parenchyma were measured using DWI with
      relatively low b factors (b = 0.01 and 128.01 seconds/mm(2)) and were compared
      among the HAI scores and among patients with cirrhosis, chronic hepatitis, and
      normal liver function. RESULTS: The ADCs decreased as the fibrosis score in the
      HAI increased, and the correlation was statistically significant (P < 0.0001). No
      relationship between the ADCs and the necroinflammation scores in the HAI was
      found. The ADCs decreased as the stage of liver disease progressed or as the
      Child-Pugh stage progressed, and these relationships were statistically
      significant (P < 0.0001). CONCLUSION: ADC measurements are potentially useful for
      the evaluation of fibrosis staging in the liver.

PMID- 15971189
TI  - Small bowel hydro-MR imaging for optimized ileocecal distension in Crohn's
      disease: should an additional rectal enema filling be performed?
AB  - PURPOSE: To assess the impact of an additional rectal enema filling in small
      bowel hydro-MRI in patients with Crohn's disease. MATERIALS AND METHODS: A total
      of 40 patients with known Crohn's disease were analyzed retrospectively: 20
      patients only ingested an oral contrast agent (group A), the other 20 subjects
      obtained an additional rectal water enema (group B). For small bowel distension,
      a solution containing 0.2% locust bean gum (LBG) and 2.5% mannitol was used. In
      all patients, a breathhold contrast-enhanced T1w three-dimensional volumetric
      interpolated breathhold examination (VIBE) sequence was acquired. Comparative
      analysis was based on image quality and bowel distension as well as signal-to
      noise ratio (SNR) measurements. MR findings were compared with those of
      conventional colonoscopy, as available (N = 25). RESULTS: The terminal ileum and
      rectum showed a significantly higher distension following the rectal
      administration of water. Furthermore, fewer artifacts were seen within group B.
      This resulted in a higher reader confidence for the diagnosis of bowel disease,
      not only in the colon, but also in the ileocecal region. Diagnostic accuracy in
      diagnosing inflammation of the terminal ileum was 100% in group B; in the
      nonenema group there were three false-negative diagnoses of terminal ileitis.
      CONCLUSION: Our data show that the additional administration of a rectal enema is
      useful in small bowel MRI for the visualization of the terminal ileum. The
      additional time needed for the enema administration was minimal, and small and
      large bowel pathologies could be diagnosed with high accuracy. Thus, we suggest
      that a rectal enema in small bowel MR imaging be considered.

PMID- 15971190
TI  - Effects of spatial and temporal resolution for MR image-guided thermal ablation
      of prostate with transurethral ultrasound.
AB  - PURPOSE: To describe approaches for determining optimal spatial and temporal
      resolutions for the proton resonance frequency shift method of quantitative
      magnetic resonance temperature imaging (MRTI) guidance of transurethral
      ultrasonic prostate ablation. MATERIALS AND METHODS: Temperature distributions of
      two transurethral ultrasound applicators (90 degrees sectored tubular and planar
      arrays) for canine prostate ablation were measured via MRTI during in vivo
      sonication, and agree well with two-dimensional finite difference model
      simulations at various spatial resolutions. Measured temperature distributions
      establish the relevant signal-to-noise ratio (SNR) range for thermometry in an
      interventional MR scanner, and are reconstructed at different resolutions to
      compare resultant temperature measurements. Various temporal resolutions are
      calculated by averaging MRTI frames. RESULTS: When noise is added to simulated
      temperature distributions for tubular and planar applicators, the minimum root
      mean squared (RMS) error is achieved by reconstructing to pixel sizes of 1.9 and
      1.7 mm, respectively. In in vivo measurements, low spatial resolution MRTI data
      are shown to reduce the noise without significantly affecting thermal dose
      calculations. Temporal resolution of 0.66 frames/minute leads to measurement
      errors of more than 12 degrees C during rapid heating. CONCLUSION: Optimizing
      MRTI pixel size entails balancing large pixel SNR gain with accuracy in
      representing underlying temperature distributions.

PMID- 15971191
TI  - Spatially-confined arterial spin-labeling with FAIR.
AB  - PURPOSE: To investigate the effectiveness of slab-selective inversion in pulsed
      arterial spin labeling with body coil excitation as a means to reduce large
      vessel contamination of the perfusion signal. MATERIALS AND METHODS: Studies were
      conducted by varying the tagging width in multislice flow-sensitive alternating
      inversion recovery (FAIR) in conjunction with body coil excitation on a Siemens
      Sonata whole-body 1.5-T scanner. The results of spatially-confined tagging were
      then compared with conventional nonselective tagging in the presence and absence
      of a bipolar gradient crusher pair in order to determine the effectiveness of
      suppressing vascular signal and to estimate the bolus width that reaches the
      capillary bed. RESULTS: It is shown in five volunteers, ages 23-38 years, that
      depending on the average velocity of the arterial blood flow in the tagging
      region, a bolus of 6-8 cm in width reaches the capillary bed at a fixed inversion
      time TI of 1.4 seconds, while a bolus of 11.2-16.5 cm in width enters the imaging
      region. Further, noticeable velocity differences have been found among the
      participating subjects, with averages ranging from 10.1 to 13.9 cm/second.
      CONCLUSION: The data suggest that it is advantageous to replace nonselective
      global tagging in FAIR perfusion imaging with body coil excitation by spatially
      confined tagging to reduce undesired residual tagged blood in large vessels.

PMID- 15971192
TI  - Cardiac CINE imaging with IDEAL water-fat separation and steady-state free
      precession.
AB  - PURPOSE: To decompose multicoil CINE steady-state free precession (SSFP) cardiac
      images acquired at short echo time (TE) increments into separate water and fat
      images, using an iterative least-squares "Dixon" (IDEAL) method. MATERIALS AND
      METHODS: Multicoil CINE IDEAL-SSFP cardiac imaging was performed in three
      volunteers and 15 patients at 1.5 T. RESULTS: Measurements of signal-to-noise
      ratio (SNR) matched theoretical expectations and were used to optimize
      acquisition parameters. TE increments of 0.9-1.0 msec permitted the use of
      repetition times (TRs) of 5 msec or less, and provided good SNR performance of
      the water-fat decomposition, while maintaining good image quality with a minimum
      of banding artifacts. Images from all studies were evaluated for fat separation
      and image quality by two experienced radiologists. Uniform fat separation and
      diagnostic image quality was achieved in all images from all studies. Examples
      from volunteers and patients are shown. CONCLUSION: Multicoil IDEAL-SSFP imaging
      can produce high quality CINE cardiac images with uniform water-fat separation,
      insensitive to Bo inhomogeneities. This approach provides a new method for
      reliable fat-suppression in cardiac imaging.

PMID- 15971193
TI  - Evaluation of two-dimensional electrophoresis and liquid chromatography--tandem
      mass spectrometry for tissue-specific protein profiling of laser-microdissected
      plant samples.
AB  - Laser microdissection (LM) allows the collection of homogeneous tissue- and cell
      specific plant samples. The employment of this technique with subsequent protein
      analysis has thus far not been reported for plant tissues, probably due to the
      difficulties associated with defining a reasonable cellular morphology and, in
      parallel, allowing efficient protein extraction from tissue samples. The
      relatively large sample amount needed for successful proteome analysis is an
      additional issue that complicates protein profiling on a tissue- or even cell
      specific level. In contrast to transcript profiling that can be performed from
      very small sample amounts due to efficient amplification strategies, there is as
      yet no amplification procedure for proteins available. In the current study, we
      compared different tissue preparation techniques prior to LM/laser pressure
      catapulting (LMPC) with respect to their suitability for protein retrieval. Cryo
      sectioning was identified as the best compromise between tissue morphology and
      effective protein extraction. After collection of vascular bundles from
      Arabidopsis thaliana stem tissue by LMPC, proteins were extracted and subjected
      to protein analysis, either by classical two-dimensional gel electrophoresis (2
      DE), or by high-efficiency liquid chromatography (LC) in conjunction with tandem
      mass spectrometry (MS/MS). Our results demonstrate that both methods can be used
      with LMPC collected plant material. But because of the significantly lower sample
      amount required for LC-MS/MS than for 2-DE, the combination of LMPC and LC-MS/MS
      has a higher potential to promote comprehensive proteome analysis of specific
      plant tissues.

PMID- 15971194
TI  - Stem cell proteomes: a profile of human mesenchymal stem cells derived from
      umbilical cord blood.
AB  - Multipotent mesenchymal stem cells (MSCs) derived from human umbilical cord blood
      (UCB) represent promising candidates for the development of future strategies in
      cellular therapy. To create a comprehensive protein expression profile for UCB
      MSCs, one UCB unit from a full-term delivery was isolated from the unborn
      placenta, transferred into culture, and their whole-cell protein fraction was
      subjected to two-dimensional electrophoresis (2-DE). Unambiguous protein
      identification was achieved with peptide mass fingerprinting matrix-assisted
      laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS),
      peptide sequencing (MALDI LIFT-TOF/TOF MS), as well as gel-matching with
      previously identified databases. In overall five replicate 2-DE runs, a total of
      2037 +/- 437 protein spots were detected of which 205 were identified
      representing 145 different proteins and 60 isoforms or post-translational
      modifications. The identified proteins could be grouped into several functional
      categories, such as metabolism, folding, cytoskeleton, transcription, signal
      transduction, protein degradation, detoxification, vesicle/protein transport,
      cell cycle regulation, apoptosis, and calcium homeostasis. The acquired proteome
      map of nondifferentiated UCB-MSCs is a useful inventory which facilitates the
      identification of the normal proteomic pattern as well as its changes due to
      activated or suppressed pathways of cytosolic signal transduction which occur
      during proliferation, differentiation, or other experimental conditions.

PMID- 15971195
TI  - Enrichment of low-abundant serum proteins by albumin/immunoglobulin G
      immunoaffinity depletion under partly denaturing conditions.
AB  - We present a simple protocol for affinity depletion to remove the two most
      abundant serum proteins, albumin and immunoglobulin G (IgG). Under native
      conditions, albumin/IgG were efficiently removed and several proteins were
      enriched as shown by two-dimensional electrophoresis (2-DE). Besides that, partly
      denaturing conditions were established by adding 5 or 20% acetonitrile (ACN) in
      order to disrupt the binding of low-molecular-weight (LMW) proteins to the
      carrier proteins albumin/IgG. 2-DE results showed that the total number of
      detected LMW proteins increased under denaturing conditions when compared to
      native conditions. Interestingly, the presence of 5% ACN in serum revealed better
      enrichment of LMW proteins when compared to 20% ACN condition. Seven randomly
      distributed spots in albumin/IgG depleted serum samples under 5% ACN condition
      were picked from the 2-DE gels and identified by mass spectrometry (MS). The
      intensity of five LMW protein spots increased under denaturing conditions when
      compared to native conditions. Three of the seven identified spots (serum amyloid
      P, vitamin D-binding protein, and transthyretin) belong to a group of relatively
      low-abundant proteins, which make up only 1% of all serum proteins. The method
      presented here improves the resolution of the serum proteome by increasing the
      number of visualized spots on 2-D gels and allowing the detection and MS
      identification of LMW proteins and proteins of lower abundance.

PMID- 15971196
TI  - Cyclin D1 polymorphism (G870A) and risk for esophageal adenocarcinoma.
AB  - BACKGROUND: To investigate individual susceptibility to gastroesophageal reflux
      disease, Barrett esophagus, and esophageal adenocarcinoma, the authors studied
      the frequency of the common G870A polymorphism of CCND1, which encodes cyclin D1,
      a key cell cycle regulatory protein. METHODS: The study population included 307
      patients who were enrolled in a prospective case-control study to evaluate
      lifestyle risk factors and molecular alterations in gastroesophageal reflux
      disease (n = 126 patients), Barrett esophagus (n = 125 patients), and esophageal
      adenocarcinoma (n = 56 patients). A control group included 95 strictly
      asymptomatic individuals. Genomic DNA was extracted from cases and controls, and
      polymerase chain reaction was used to amplify exon 4 of CCND1. After digestion
      with BsrI, acrylamide gel electrophoresis was used to identify the wild type and
      common G870A polymorphic alleles. The frequency of alleles (G/G, G/A, A/A) was
      compared between cases and controls. Immunohistochemistry was used to study
      cyclin D1 distribution in among patients in the case group. RESULTS: Compared
      with the asymptomatic control group, and adjusted for age and gender, increasing
      frequencies were seen for the A/A genotype in patients with gastroesophageal
      reflux disease (odds ratio [OR], 2.83; 95% confidence interval [95% CI], 1.09
      7.34), Barrett esophagus (OR, 3.69; 95% CI, 1.46-9.29), and esophageal
      adenocarcinoma (OR, 5.99; 95% CI, 1.86-18.96). No association was seen between
      genotype and cyclin D1 overexpression. CONCLUSIONS: The CCND1 A/A genotype was
      associated with increased risk for gastroesophageal reflux disease, Barrett
      esophagus, and esophageal adenocarcinoma. The contribution of this polymorphism
      to susceptibility of defined stages of progression to esophageal adenocarcinoma
      suggested potential application in endoscopic Barrett surveillance programs.

PMID- 15971197
TI  - Significance of myelofibrosis in early chronic-phase, chronic myelogenous
      leukemia on imatinib mesylate therapy.
AB  - BACKGROUND: Myelofibrosis is associated historically with a poor prognosis in
      patients with chronic myelogenous leukemia (CML). Its significance in the recent
      era of effective therapy with imatinib mesylate is unknown. METHODS: The current
      study evaluated the significance of the degree of pretreatment myelofibrosis on
      response and survival with imatinib therapy in patients with newly diagnosed CML.
      The study group comprised 198 patients with newly diagnosed Philadelphia
      chromosome-positive, chronic-phase CML treated with imatinib mesylate therapy.
      They were analyzed for the prognostic significance of bone marrow reticulin
      fibrosis. RESULTS: Severe reticulin (Grade 3-4) fibrosis was observed in 75
      patients (38%): Grade 3 in 46 (23%) patients and Grade 4 in 29 (15%) patients.
      There was a trend towards a lower incidence of a complete cytogenetic response in
      patients with Grade 4 reticulin fibrosis (76% vs. 89%; P = 0.07), and a
      significantly worse survival (estimated 3-year survival rate of 87% vs. 97%; P =
      0.04). CONCLUSIONS: Although the prognostic significance of severe reticulin
      fibrosis in patients with newly diagnosed CML receiving imatinib therapy was
      better, 15% of patients with Grade 4 reticulin fibrosis still had a worse
      outcome.

PMID- 15971198
TI  - Effect of neutropenia on the impact of a cognitive-behavioral intervention for
      symptom management.
AB  - BACKGROUND: Trials of cognitive-behavioral interventions (CBI) designed to reduce
      symptom severity or improve dimensions of quality of life seldom consider how the
      side effects of treatment or the complications imposed by the disease or
      treatment may moderate the impact of the trial on the designated outcome. To
      address this issue, the moderating effect of neutropenia on the impact of a CBI
      for reducing symptom severity was evaluated among patients with cancer undergoing
      chemotherapy. METHODS: The authors described the impact of a randomized trial of
      a 10-contact, 20-week CBI on symptom severity, as well as the moderating effect
      of a neutropenic episode on symptom severity at 20 weeks. Severity scores were
      based on sum scores (0-10) for 15 symptoms. RESULTS: There was an effect for age
      (younger) and group on severity at 20 weeks and an interaction between
      neutropenia and group. Among patients with no evidence of neutropenia, those in
      the experimental arm had a 9-point lower severity score at 20 weeks. Among
      patients who experienced neutropenia, differences in symptom severity by arm of
      the trial were < 3 points. Further, fatigue, fever, and pain were more prevalent
      among patients with neutropenia. CONCLUSIONS: Patients who experienced
      neutropenia did not benefit from a CBI to lower symptoms. The overall effect of
      this intervention came almost exclusively from patients without neutropenia.

PMID- 15971199
TI  - Magnetic resonance imaging reveals functional diversity of the vasculature in
      benign and malignant breast lesions.
AB  - BACKGROUND: Tumor perfusion through the microvascular network can be imaged
      noninvasively by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
      The objective of the current study was to quantify the microvascular perfusion
      parameters in various human breast lesions and to determine whether they varied
      between benign lesions and malignancy and whether they were altered with
      increased invasiveness. METHODS: Perfusion parameters in 22 benign fibrocystic
      changes, 15 ductal carcinomas in situ (DCIS), 30 infiltrating ductal carcinomas
      (IDC), and 22 fibroadenomas were measured using high-resolution DCE-MRI. Pixel-by
      pixel image analysis yielded parametric images of two perfusion indicators: the
      influx transcapillary transfer constant (k(trans)) and the efflux transcapillary
      rate constant (k(ep)). Correlations of lesion type and perfusion parameters were
      calculated using Spearman correlation. Logistic regression analysis evaluated the
      best predictors of the kinetic parameters that differentiate between IDC and
      benign lesions. RESULTS: The perfusion parameters exhibited a progressive
      increase from benign fibrocystic changes to DCIS and IDC, with a significant
      correlation between lesion type and the parameters' values (range of correlation
      coefficients, 0.56-0.76; P < 0.0001). In addition, k(trans) increased from low
      grade DCIS to high-grade DCIS. Fibroadenomas were characterized uniquely by high
      k(trans) but low k(ep). Stepwise logistic regression selected k(trans) as the
      best predictor for distinguishing benign fibrocystic changes from IDC, yielding
      93% sensitivity and 96% specificity. CONCLUSIONS: The microvascular perfusion
      parameters in breast lesions were elevated with invasiveness. Quantification of
      these parameters using high-resolution DCE-MRI was helpful for differentiating
      between breast lesions and should improve breast carcinoma diagnosis.

PMID- 15971200
TI  - S100beta as a predictor of brain metastases: brain versus cerebrovascular damage.
AB  - BACKGROUND: The identification of brain metastases in patients with malignant
      disease has important implications for determining their treatment and prognosis.
      Asymptomatic metastatic brain tumors may be detected by surveillance imaging
      techniques, but longitudinal follow-up of patients who are at risk is sporadic
      primarily due to cost. Because the development of brain metastases is accompanied
      and detected by extravasation of contrast agents across the blood-brain barrier
      (BBB), the authors hypothesized that peripheral analysis of the BBB indicator
      S100beta may be useful as a screening tool for brain metastases in patients who
      have no neurologic symptoms. METHODS: Thirty-eight patients were enrolled for the
      current study. All patients had newly diagnosed lung carcinoma and had no
      neurologic symptoms or known history of brain metastasis. Patients underwent an
      initial magnetic resonance imaging (MRI) scans and S100beta blood tests. S100beta
      tests were repeated in a subset of patients at the time of routine follow-up MRI
      scans. RESULTS: Based on imaging studies and on serum S100beta analyses, the
      patients were divided in 3 categories: 1) patients with normal S100beta levels
      (0.08 +/- 0.02 microg/L; n = 22 patients) and normal MRI scans; 2) patients with
      elevated S100beta levels (0.5 +/- 0.28 microg/L; n = 8 patients) and pronounced
      microvascular changes on MRI scans but with no metastases; and 3) patients with
      elevated S100beta levels (0.28 +/- 0.19 microg/L; n = 7 patients) and metastatic
      brain tumor(s) on MRI scans. CONCLUSIONS: Because of the significant overlap in
      S100beta levels between patients with cerebral microvascular diseases and
      patients with brain metastases, the authors concluded that the serum S100beta
      level may be used as a surveillance tool to predict or detect brain metastases if
      appropriate prescreening radiologic tests are obtained and if patients who are
      candidates for false-positive results are identified and excluded.

PMID- 15971201
TI  - Phosphorylation of either Ser16 or Thr30 does not disrupt the structure of the
      Itch E3 ubiquitin ligase third WW domain.

PMID- 15971202
TI  - Binding MOAD (Mother Of All Databases).
AB  - Binding MOAD (Mother of All Databases) is the largest collection of high-quality,
      protein-ligand complexes available from the Protein Data Bank. At this time,
      Binding MOAD contains 5331 protein-ligand complexes comprised of 1780 unique
      protein families and 2630 unique ligands. We have searched the crystallography
      papers for all 5000+ structures and compiled binding data for 1375 (26%) of the
      protein-ligand complexes. The binding-affinity data ranges 13 orders of
      magnitude. This is the largest collection of binding data reported to date in the
      literature. We have also addressed the issue of redundancy in the data. To create
      a nonredundant dataset, one protein from each of the 1780 protein families was
      chosen as a representative. Representatives were chosen by tightest binding, best
      resolution, etc. For the 1780 "best" complexes that comprise the nonredundant
      version of Binding MOAD, 475 (27%) have binding data. This significant collection
      of protein-ligand complexes will be very useful in elucidating the biophysical
      patterns of molecular recognition and enzymatic regulation. The complexes with
      binding-affinity data will help in the development of improved scoring functions
      and structure-based drug discovery techniques. The dataset can be accessed at
      http://www.BindingMOAD.org.

PMID- 15971203
TI  - Molecular modeling of cardiac glycoside binding by the human sequence monoclonal
      antibody 1B3.
AB  - The amino acid sequences of the heavy- and light-chain variable regions of the
      high-affinity human sequence antidigoxin monoclonal antibody 1B3 (mAb 1B3) were
      determined, and a structural model for the mAb's variable region was developed by
      homology modeling techniques. The structural model provided the basis for
      computationally docking digoxin and eight related cardiac glycosides into the
      putative binding site of mAb 1B3. Analysis of the consensus binding mode obtained
      for digoxin showed that the cardenolide moiety of digoxin is deeply embedded in a
      predominantly hydrophobic, narrow cavity, whereas the terminal, gamma
      carbohydrate group is solvent-exposed. The docking results indicated that the
      primary driving forces for digoxin binding by mAb 1B3 are hydrophobic
      interactions with the digoxin steroid ring system and hydrogen bonds with the
      digitoxose groups. The binding model accounts for the experimentally observed
      variations in mAb 1B3 binding affinity for various structural analogs of digoxin
      used previously to develop a 3D structure-activity relationship model of drug
      binding (Farr CD, Tabet MR, Ball WJ Jr, Fishwild DM, Wang X, Nair AC, Welsh WJ.
      Three-dimensional quantitative structure-activity relationship analysis of ligand
      binding to human sequence antidigoxin monoclonal antibodies using comparative
      molecular field analysis. J Med Chem 2002;45:3257-3270). In particular, the
      hydrogen bond pattern is consistent with the unique sensitivity of mAb 1B3's
      binding affinity to the number of sugar residues present in a cardiac glycoside.
      The hydrophobic environment about the steroid moiety of digoxin is compatible
      with the mAb's reduced affinity for ligands that possess hydrophilic hydroxyl and
      acetyl group modifications in this region. The model also indicated that most of
      the amino acid residues in contact with the ligand reside in or about the three
      complementarity determining regions (CDRs) of the heavy chain and the third CDR
      of the light chain. A comparison of the 1B3 binding model with the crystal
      structures of two murine antidigoxin mAbs revealed similar binding patterns used
      by the three mAbs, such as a high frequency of occurrence of aromatic,
      hydrophobic residues in the CDRs and a dominant role of the heavy chain CDR3 in
      antigen binding.

PMID- 15971204
TI  - Flexibility of prolyl oligopeptidase: molecular dynamics and molecular framework
      analysis of the potential substrate pathways.
AB  - The flexibility of prolyl oligopeptidase has been investigated using molecular
      dynamics (MD) and molecular framework approaches to delineate the route of the
      substrate to the active site. The selectivity of the enzyme is mediated by a
      seven-bladed beta-propeller that in the crystal structure does not indicate the
      possible passage for the substrate to the catalytic center. Its open topology
      however, could allow the blades to move apart and let the substrate into the
      large central cavity. Flexibility analysis of prolyl oligopeptidase structure
      using the FIRST (Floppy Inclusion and Rigid Substructure Topology) approach and
      the atomic fluctuations derived from MD simulations demonstrated the rigidity of
      the propeller domain, which does not permit the substrate to approach the active
      site through this domain. Instead, a smaller tunnel at the inter-domain region
      comprising the highly flexible N-terminal segment of the peptidase domain and a
      facing hydrophilic loop from the propeller (residues 192-205) was identified by
      cross-correlation analysis and essential dynamics as the only potential pathway
      for the substrate. The functional importance of the flexible loop has been also
      verified by kinetic analysis of the enzyme with a split loop. Catalytic effect of
      engineered disulfide bridges was rationalized by characterizing the concerted
      motions of the two domains.

PMID- 15971205
TI  - G-protein-coupled receptor domain overexpression in Halobacterium salinarum: long
      range transmembrane interactions in heptahelical membrane proteins.
AB  - The aminergic alpha(2b)-adrenergic receptor (alpha(2b)-AR) third intracellular
      loop (alpha(2b)-AR 3i) mediates receptor subcellular compartmentalization and
      signal transduction processes via ligand-dependent interaction with G(i)- and
      G(o)- proteins. To understand the structural origins of these processes we
      engineered several lengths of alpha(2b)-AR 3i into the third intracellular loop
      of the proton pump bacteriorhodopsin (bR) and produced the fusion proteins in
      quantities suitable for physical studies. The fusion proteins were expressed in
      the Archaeon Halobacterium salinarum and purified. A highly expressed fusion
      protein was crystallized from bicelles and diffracted to low resolution on an in
      house diffractometer. The bR-alpha(2b)-AR 3i(203-292) protein possessed a
      photocycle slightly perturbed from that of the wild-type bR. The first half of
      the fusion protein photocycle, correlated with proton release, is accelerated by
      a factor of 3, whereas the second half, correlated with proton uptake, is
      slightly slower than wild-type bR. In addition, there is a large decrease in the
      pK(a), (from 9.6 to 8.3) of the terminal proton release group in the unphotolyzed
      state of bR-alpha(2b)-AR 3i as deduced from the pH-dependence of the M-formation.
      Perturbation of a cytoplasmic loop has thus resulted in the perturbation of
      proton release at the extracellular surface. The current work indicates that long
      range and highly coupled intramolecular interactions exist that are capable of
      "transducing" structural perturbations (e.g., signals) across the cellular
      membrane. This gene fusion approach may have general applicability for physical
      studies of G-protein-coupled receptor domains in the context of the bR structural
      scaffold.

PMID- 15971206
TI  - Molecular dynamics study of water penetration in staphylococcal nuclease.
AB  - The ionization properties of Lys and Glu residues buried in the hydrophobic core
      of staphylococcal nuclease (SN) suggest that the interior of this protein behaves
      as a highly polarizable medium with an apparent dielectric constant near 10. This
      has been rationalized previously in terms of localized conformational relaxation
      concomitant with the ionization of the internal residue, and with contributions
      by internal water molecules. Paradoxically, the crystal structure of the SN V66E
      variant shows internal water molecules and the structure of the V66K variant does
      not. To assess the structural and dynamical character of interior water molecules
      in SN, a series of 10-ns-long molecular dynamics (MD) simulations was performed
      with wild-type SN, and with the V66E and V66K variants with Glu66 and Lys66 in
      the neutral form. Internal water molecules were identified based on their
      coordination state and characterized in terms of their residence times, average
      location, dipole moment fluctuations, hydrogen bonding interactions, and
      interaction energies. The locations of the water molecules that have residence
      times of several nanoseconds and display small mean-square displacements agree
      well with the locations of crystallographically observed water molecules.
      Additional, relatively disordered water molecules that are not observed
      crystallographically were found in internal hydrophobic locations. All of the
      interior water molecules that were analyzed in detail displayed a distribution of
      interaction energies with higher mean value and narrower width than a bulk water
      molecule. This underscores the importance of protein dynamics for hydration of
      the protein interior. Further analysis of the MD trajectories revealed that the
      fluctuations in the protein structure (especially the loop elements) can strongly
      influence protein hydration by changing the patterns or strengths of hydrogen
      bonding interactions between water molecules and the protein. To investigate the
      dynamical response of the protein to burial of charged groups in the protein
      interior, MD simulations were performed with Glu66 and Lys66 in the charged
      state. Overall, the MD simulations suggest that a conformational change rather
      than internal water molecules is the dominant determinant of the high apparent
      polarizability of the protein interior.

PMID- 15971207
TI  - Increasing the molecular contacts between maurotoxin and Kv1.2 channel augments
      ligand affinity.
AB  - Scorpion toxins interact with their target ion channels through multiple
      molecular contacts. Because a "gain of function" approach has never been
      described to evaluate the importance of the molecular contacts in defining toxin
      affinity, we experimentally examined whether increasing the molecular contacts
      between a toxin and an ion channel directly impacts toxin affinity. For this
      purpose, we focused on two scorpion peptides, the well-characterized maurotoxin
      with its variant Pi1-like disulfide bridging (MTX(Pi1)), used as a molecular
      template, and butantoxin (BuTX), used as an N-terminal domain provider. BuTX is
      found to be 60-fold less potent than MTX(Pi1) in blocking Kv1.2 (IC(50) values of
      165 nM for BuTX versus 2.8 nM for MTX(Pi1)). Removal of its N-terminal domain
      (nine residues) further decreases BuTX affinity for Kv1.2 by 5.6-fold, which is
      in agreement with docking simulation data showing the importance of this domain
      in BuTX-Kv1.2 interaction. Transfer of the BuTX N-terminal domain to MTX(Pi1)
      results in a chimera with five disulfide bridges (BuTX-MTX(Pi1)) that exhibits 22
      fold greater affinity for Kv1.2 than MTX(Pi1) itself, in spite of the lower
      affinity of BuTX as compared to MTX(Pi1). Docking experiments performed with the
      3-D structure of BuTX-MTX(Pi1) in solution, as solved by (1)H-NMR, reveal that
      the N-terminal domain of BuTX participates in the increased affinity for Kv1.2
      through additional molecular contacts. Altogether, the data indicate that acting
      on molecular contacts between a toxin and a channel is an efficient strategy to
      modulate toxin affinity.

PMID- 15971208
TI  - The utility of B72.3, carcinoembryonic antigen, and Leu M-1 in cell blocks: an
      adjunct to fine-needle aspiration diagnosis of bronchioloalveolar carcinoma of
      the lung.
AB  - BACKGROUND: The distinction of bronchioloalveolar carcinoma (BAC) from atypical
      adenomatous hyperplasia (AAH) or reactive alveolar cell hyperplasia (RAH) can be
      difficult on aspiration cytology, even when cell block preparations are
      available. The authors evaluated the usefulness of B72.3, carcinoembryonic
      antigen (CEA), and Leu M-1 immunostains in differentiating BAC, AAH, and RAH.
      METHODS: Immunostains for B72.3, CEA, and Leu M-1 were performed on cell block
      sections from 11 lung lesions that were diagnosed cytologically as BAC (6
      lesions) and "atypical cells, cannot exclude BAC" (5 lesions). Ten histologic
      sections of AAH and 8 histologic sections of RAH also were stained. RESULTS:
      Among the six lesions that had an unequivocal cytologic diagnosis of BAC, all
      sections were positive for two of three immunostains. Tissue follow-up confirmed
      BAC in all six lesions. Among the five lesions that were diagnosed as "atypical
      cells, cannot exclude BAC," four lesions were positive for two of three
      immunostains, and one lesion was negative for all three immunostains. Subsequent
      tissue follow-up confirmed BAC in four of these lesions. Follow-up histology of
      the wedge resection on the lesion in the atypical category that was negative for
      B72.3, CEA, and Leu M-1 showed only AAH. All 10 lesions that had a histologic
      diagnosis of AAH and 8 lesions that had a histologic diagnosis RAH were negative
      for B72.3, CEA, and Leu M-1. CONCLUSIONS: Positive staining for at least 2
      immunostains among B72.3, CEA, and Leu M-1 provided strong supportive evidence
      for the diagnosis of BAC, and a negative result for all 3 immunostains was
      helpful in excluding BAC and in differentiating BAC from AAH and RAH.

PMID- 15971209
TI  - Reply to "Crista aortae ascendentis, ascending aortic fold or Rindfleisch's fold-
      an enigma".

PMID- 15971210
TI  - Interaction between the movement protein of barley yellow dwarf virus and the
      cell nuclear envelope: role of a putative amphiphilic alpha-helix at the N
      terminus of the movement protein.
AB  - The open reading frame 4 (ORF 4) gene product of barley yellow dwarf virus (BYDV)
      may act as a movement protein (MP) by assisting the transport of viral genomic
      RNA across the nuclear envelope (NE) of host plant cells. To investigate
      interactions between BYDV MP and the NE, wild-type and mutant open reading frame
      (ORF 4)-green fluorescent protein (GFP) fusion cistrons were expressed in insect
      cells. A fusion protein expressed by the wild-type ORF 4-GFP cistron associated
      with the NE and caused protrusions from its surface. The fusion protein expressed
      by the mutant ORF 4-GFP cistron lacked a putative amphiphilic alpha-helix at its
      N-terminus and although associating with the NE, showed decreased levels of
      protrusions. A peptide homologue of this putative alpha-helix induced an increase
      of 7 degrees C in the phase transition temperature of dimyrystoyl
      phosphatidylserine (DMPS) membranes, accompanied by a decrease in membrane
      fluidity, but exhibited no significant interaction with either dimyristoyl
      phosphatidylcholine (DMPC) or dimyristoyl phosphatidylethanolamine (DMPE)
      membranes. These results strongly support the view that BYDV MP may interact with
      the NE to help transport viral genomic RNA into the nuclear compartment. This
      function of BYDV MP appears to involve protrusions on the surface of the NE and
      may require the presence of an N-terminal amphiphilic alpha-helix, which is
      speculated to destabilize membranes, thereby assisting the entry of BYDV-GAV into
      the nuclear compartment.

PMID- 15971213
TI  - Is the posterior belly of the digastric muscle palpable? A qualitative systematic
      review of the literature.
AB  - Palpation of the posterior belly of the digastric muscle in the postmandibular
      region is included in many study protocols and examination schemes of the
      masticatory system. The aim of the present investigation was to systematically
      search the dental/medical literature to find evidence for the palpability of this
      muscle. In August 2004, a systematic search was carried out using different
      electronic databases (PubMed, Cochrane Library, Web of Science, Japana Centra
      Revuo Medicina, MedPilot, Latin American and Caribbean Health Sciences, and three
      on-line databases of dental journals not listed currently in Medline),
      supplemented by manual search in the Austrian journal Stomatologie. Additional
      manual searches were carried out in the Journal of Orofacial Pain and Journal of
      Dental Research to identify pertinent abstracts of scientific congresses. One
      relevant hit was found in the Japanese database. The manual search showed one
      pertinent congress abstract. In both publications, the authors concluded that due
      to anatomical reasons the posterior belly of the digastric muscle was not
      palpable. Hence, evidence is lacking that the posterior digastric muscle is
      accessible to palpation. Because the postmandibular region is usually tender upon
      palpation, a high incidence of positive findings can be expected even among
      healthy subjects. This may lead to wrong clinical judgments, possibly provoking
      unnecessary diagnostic and therapeutic measures.

PMID- 15971214
TI  - Anatomic study of the blood supply of perioral region.
AB  - The use of flaps to reconstruct lip defects requires detailed knowledge of the
      local vasculature. New flaps for surgery around the mouth can be devised if the
      surgeon knows the distribution of the perioral arterial branches. Examination of
      the anatomy of perioral branches of the facial artery (FA) confirmed the
      consistent presence of septal and alar branches in the upper lip and a
      labiomental branch in the lower lip. Mucosal flaps from the upper lip based on
      the deep septal branch or the alar branch of the FA can be used to restore lower
      lip defects. A composite flap from the lower lip supplied by the labiomental
      branch of the FA can be used to restore combined defects of the upper lip and
      nose or partial defects of the lower lip. We studied the vascular anatomy of the
      perioral region in 25 cadaver dissections. Fixation was by 10% formaldehyde
      solution. Red latex was injected into the common carotid arteries before
      dissection. In the 50 specimens, the primary supplying vessels were identified
      and the size and distribution of the vessels were investigated. The FA was
      symmetrical in 17 (68%) of 25 heads. It terminated as an angular facial vessel in
      11 (22%), as a nasal facial vessel in 30 (60%), as an alar vessel in six (12%),
      and as a superior labial vessel in two (4%) facial halves. It terminated as a
      hypoplastic type of FA in one (2%) facial half. The average external diameter of
      the superior labial artery (SLA) was 1.6 mm (min-max: 0.6-2.8 mm) at its origin.
      The origin of the SLA was superior to the angle of the mouth in 34 of 47
      specimens (72.3%), and at the angle of the mouth in 13 of 47 specimens (27.7%).
      In two of the remaining three specimens, the SLA was the continuation of the FA
      and the other was of the hypoplastic type. The SLA supplied the columellar
      branches in all specimens except for the hypoplastic type (49 specimens).
      Columellar branches were classified according to their number and their type. In
      five specimens (10%) the inferior labial artery (ILA) was not found. In the other
      specimens, the site of origin of the ILA varied between the lower margin of the
      mandible and the corner of the mouth. Its external diameter measured min-max: 0.5
      1.5 mm. The ILA arose from the FA above the angle of mouth in 4 specimens (8%),
      inferior to the angle of mouth in 11 specimens (22%), and at angle of mouth in 30
      specimens (60%). We observed that the labiomental arteries, which formed
      anastomoses between the FA, ILA, and submental artery, showed variations in their
      course in the labiomental region. We suggest that knowledge of the location of
      arteries with respect to easily identifiable landmarks will help to avoid
      complications at surgery.

PMID- 15971215
TI  - The costotransverse ligaments in human: a detailed anatomical study.
AB  - This study provides a more detailed description of the costotransverse ligaments
      in human, aimed at investigating some controversial data and disclosing some
      lacking information concerning the anatomy of such ligaments. Complete spinal
      segments from the seventh cervical to the first lumbar vertebra were removed from
      15 human cadavers (8 males, 7 females) with a mean age of 55 years. The
      costotransverse ligaments were exposed, bilaterally, at each vertebral level,
      using a posterior and an anterior approach to the spine. The lateral
      costotransverse, the superior costotransverse, and the costotransverse ligaments
      were identified and described. A rudimentary superior costotransverse ligament
      related to the first rib was also identified. In addition, two thick ligamentous
      bands were clearly observed in all dissected specimens and were referred to in
      the study as inferior and posterior costotransverse ligaments. Both bands were
      subjected to a detailed anatomical study. The importance of such ligaments in
      maintaining stability of the spine was also discussed.

PMID- 15971216
TI  - Neurovascular anatomy and variation in the fourth, fifth, and sixth intercostal
      spaces in the mid-axillary line: a cadaveric study in respect of chest drain
      insertion.
AB  - Chest drains are normally inserted in the fifth intercostal space in the mid
      axillary line. The classical technique for chest drain insertion involves
      locating the drain in an interspace just superior to the inferior rib, so as to
      avoid the neurovascular bundle. While teaching thoracic wall anatomy on cadavers,
      considerable variation was noted in the position of the neurovascular bundles,
      frequently lying well away from the generally accepted subcostal groove. We
      endeavoured to perform a comprehensive cadaveric study of the neurovascular
      relationships in the mid-axillary line in the fifth and adjacent spaces to try to
      describe a 'Safe Zone' for drain insertion to minimise damage to associated
      structures. The idea that the neurovascular bundle is safely protected in the
      subcostal groove should be dispelled, as should the concept that there is nothing
      to damage in the zone immediately superior to the inferior rib. Clinicians should
      be aware that the Safe Zone is narrower than hitherto appreciated and should be
      between 50-70% of the way down an interspace to avoid the variably positioned
      superior intercostal neurovascular bundle and the inferior collateral artery.

PMID- 15971217
TI  - Novel surgical approach to the carpal tunnel: cadaveric feasibility study.
AB  - Carpal tunnel syndrome is the most common entrapment neuropathy dealt with by the
      clinician. Multiple techniques have been used to surgically treat this
      pathological condition and all of these approach the carpal tunnel from the
      palmar surface of the hand or wrist. We have developed a novel endoscopic
      approach to the carpal tunnel utilizing a dorsal approach that necessitates a
      good appreciation of the anatomy of this region. This approach was carried out in
      10 hands. Through a single dorsal incision we were able to transect the flexor
      retinaculum in all specimens without obvious damage to neural or vascular
      tissues. The microscissors used in our study were found to be too delicate for
      transection of the flexor retinaculum thus another cutting tool should be
      considered. Our dorsal approach with visualization of the internal aspect of the
      flexor retinaculum may obviate many of the complications that are seen with the
      current techniques used to surgically treat carpal tunnel syndrome such as injury
      to the median nerve and its branches. Clinical trials are now necessary with
      prospective randomized studies that will determine which techniques are most
      efficacious and minimize complications most effectively.

PMID- 15971218
TI  - Clinical anatomy of the inferior phrenic artery.
AB  - The majority of anatomical textbooks of gross anatomy offer very little
      information concerning the anatomy and distribution of the inferior phrenic
      artery (IPA). In the last decade, however, increased numbers of reports have
      appeared with reference to the arterial supply of hepatocellular carcinoma (HCC).
      The IPA is a major source of collateral or parasitized arterial supply to this
      type of carcinoma, second only to the hepatic artery. The aim of this study was
      to identify the origin and distribution of the IPA (right and left), in normal
      and pathological cases, and to apply such findings to the clinical scenario of
      treating hepatic cancer. We have examined 300 formalin-fixed adult cadavers
      lacking abdominal pathology, and 30 cadavers derived from patients with HCC.
      Dissections in normal cadavers showed that the right IPA originated from the: a)
      celiac trunk in 40% of the specimens; b) aorta in 38%; c) renal in 17%; d) left
      gastric in 3%; and e) hepatic artery proper in 2% of the specimens. The left IPA
      originated from the: a) celiac trunk in 47%; b) aorta in 45%; c) renal in 5%; d)
      left gastric in 2%; and e) hepatic artery proper in 1% of the specimens. The IPA
      gave rise to eight notable branches: ascending, descending, inferior vena cava,
      superior suprarenal, middle suprarenal, esophageal, diaphragmatic hiatal, and
      accessory splenic. The right IPA was always associated with HCC and served as the
      major collateral artery adjunct to the hepatic artery. These findings could have
      major implications in the transcatheter embolization of HCC patients.

PMID- 15971219
TI  - Case of double superior vena cava.
AB  - A 23-year-old male patient who had no history of any previous medical illness was
      noted to have a widened mediastinum on chest X-ray undertaken as part of a
      routine medical evaluation. A computer tomographic (CT) scan confirmed the
      widened mediastinum to be due to a double superior vena cava (SVC). No further
      investigations were undertaken. The patient was noted to be well when re-assessed
      3 years later.

PMID- 15971220
TI  - Rare variations of the left subclavian artery.
AB  - The subclavian artery is a major constituent of the blood circulatory system. Its
      position in the root of the neck and its course through the interscalene triangle
      are significant. Its branches supply divers areas in the body from the brain to
      the thorax. This case report describes an unusual range of anatomical variations
      of the course of the left subclavian artery, the origin, and absence of some of
      its branches and the concomitant abnormal course of the phrenic nerve. Clinical
      syndromes related to certain variations are reviewed.

PMID- 15971221
TI  - Insight into understanding the anatomical and clinical aspects of supernumerary
      rectus capitis posterior muscles.
AB  - Rectus capitis posterior muscles are located in the suboccipital triangle and
      function in extension and lateral rotation of the head and neck. There are two of
      these muscles on each side: the rectus capitis posterior major and the rectus
      capitis posterior minor. This study describes the presence of a third
      suboccipital muscle in a 55-year-old cadaver. In addition to highlighting the
      possible relationship between these muscles and cervicogenic headaches or balance
      in an individual, we also relate this observation to similar musculature in the
      cat that have been shown to effect crucial functions.

PMID- 15971222
TI  - Three-headed biceps brachii muscle associated with duplicated musculocutaneous
      nerve.
AB  - A unilateral three-headed biceps brachii muscle coinciding with an unusual
      variant of the musculocutaneous nerve was found during routine dissection of a 79
      year-old male cadaver. The supernumerary bicipital head originated from the
      antero-medial surface of the humerus just beyond the insertion of the
      coracobrachialis, and inserted into the conjoined tendon of biceps brachii.
      Associated with this muscular variant was a duplicated musculocutaneous nerve.
      The proximal musculocutaneous nerve conformed to the normal pattern only in its
      proximal part, and terminated after innervating the coracobrachialis and biceps
      brachii muscles. The distal musculocutaneous nerve arose from the median nerve in
      the lower arm, then passed laterally between the supernumerary bicipital head and
      the brachialis muscles, supplying both and terminating as the lateral cutaneous
      nerve of the forearm. The supernumerary bicipital head and the accompanying
      anomaly of the musculocutaneous nerve seem to be unique in literature.

PMID- 15971223
TI  - Survey of clinicians' attitudes to the anatomical teaching and knowledge of
      medical students.
AB  - There is considerable and ongoing debate surrounding the teaching of anatomy to
      medical students, and the anatomical knowledge of those medical students once
      they graduate. Few attempts have been made to gather the opinions of clinicians
      on this subject. A questionnaire was sent to 362 senior clinicians in hospitals
      affiliated to the University of Aberdeen. A total of 162 replies were received,
      with this sample being representative of the population of hospital consultants.
      Our results indicate that the majority of clinicians feel that the current
      anatomical education of medical students is inadequate, and below the minimum
      necessary for safe medical practice. There is widespread support among clinicians
      for more vertical integration of anatomy teaching throughout the undergraduate
      curriculum.

PMID- 15971224
TI  - Gross anatomy dissections and self-directed learning in medicine.
AB  - The Medical School of the University of Castilla-La Mancha (UCLM, Albacete Spain)
      was launched in 1998 and is the most recent one in Spain. Teaching is based on
      small groups of students (20-25 students/group). An objective-oriented self
      learning approach provides maximal autonomy and independence in the achievement
      of objectives by the students in close association with academic staff. Gross
      Anatomy courses take place in the first and second years. The one in the first
      year is a single 10-credit course, where one credit equals 10 hr of teaching
      activity. In the second year, Anatomy and Embryology are integrated with
      Physiology and Histology, and comprise 70 credits altogether. In addition, all
      students carry out two mandatory gross anatomical dissections per year, in groups
      of three students, to allow direct handling of human anatomical material.
      Students are provided with handouts containing general instructions on how to
      perform the dissection and the structures (items) that they must expose in a
      given period of time (4 hr). Afterward, a Faculty member checks the number of
      items demonstrated and the quality of the dissection. Each group submits a
      written report that contributes to the final score. We evaluated the number of
      items shown in each of two consecutive dissections for first and second year
      medical students. The data obtained indicate that students engaged in self
      directed learning through small groups working with Faculty staff are able to
      self-improve their anatomical skills.

PMID- 15971226
TI  - Stratification of the flexor retinaculum: amending vs. unnecessary.

PMID- 15971227
TI  - Clinical anatomy of the posterior maxilla pertaining to Le Fort I osteotomy in
      Thais.
AB  - This article studies the anatomy of the posterior maxilla pertaining to bone-cut
      design of Le Fort I osteotomy to avoid the injury to the descending palatine
      artery in Thais. Fifty-five skulls (38 males, 17 females) were assessed for the
      anatomical landmarks by a combination of direct inspection, computerized imaging,
      and computed tomography scan analysis. The results showed that 27.28% of the
      pterygomaxillary junction (PMJ) became synostosis. The mean heights of the PMJ,
      posterior maxilla, and maxillary tuberosity were 15.14 +/- 2.46 mm, 22.51 +/-
      3.50 mm, and 7.45 +/- 2.76 mm, respectively. The mean length of the medial sinus
      wall measuring from the piriform rim to the descending palatine canal at the Le
      Fort I level was 34.40 +/- 2.96 mm. The mean widths of the posterior incision of
      Le Fort I osteotomy at the maxillary tuberosity and PMJ were 20.38 +/- 2.82 mm
      and 11.60 +/- 1.57 mm. The mean length of the posterior maxilla was 27.18 +/-
      2.49 mm. Distances from the greater palatine foramen to the maxillary tuberosity
      incision and PMJ incision were 1.76 +/- 1.12 mm and 3.59 +/- 1.40 mm. The mean
      angle between the descending palatine canal and the hard palate was 57.33 +/-
      4.54 degrees . There were no significant differences in any measurements between
      sides and genders, except the pterygoid process width and posterior maxilla
      length of males were longer than those of females (P < 0.05). This study could
      provide better understanding of the posterior maxillary anatomy that is important
      for the bone-cut design of Le Fort I osteotomy to avoid excessive intraoperative
      and postoperative hemorrhage including ischemia of the mobilized maxilla.

PMID- 15971228
TI  - Expansion of human embryonic stem cells in defined serum-free medium devoid of
      animal-derived products.
AB  - Human embryonic stem cells (hESCs) can serve as an unlimited cell source for
      cellular transplantation and tissue engineering due to their prolonged
      proliferation capacity and their unique ability to differentiate into derivatives
      of all three-germ layers. In order to reliably and safely produce hESCs, use of
      reagents that are defined, qualified, and preferably derived from a non-animal
      source is desirable. Traditionally, mouse embryonic fibroblasts (MEFs) have been
      used as feeder cells to culture undifferentiated hESCs. We recently reported a
      scalable feeder-free culture system using medium conditioned by MEFs. The base
      and conditioned medium (CM) still contain unknown bovine and murine-derived
      components, respectively. In this study, we report the development of a hESC
      culture system that utilizes a commercially available serum-free medium (SFM)
      containing human sourced and recombinant proteins supplemented with recombinant
      growth factor(s) and does not require conditioning with feeder cells. In this
      system, which employs human laminin coated surface and high concentration of
      hbFGF, the hESCs maintained undifferentiated hESC morphology and had a twofold
      increase in expansion compared to hESCs grown in MEF-CM. The hESCs also expressed
      surface markers SSEA-4 and Tra-1-60 and maintained expression of hTERT, Oct4, and
      Cripto genes similar to cells cultured in MEF-CM. In addition, hESCs maintained
      in this culture system were able to differentiate in vitro and in vivo into cells
      of all three-germ layers. The cells maintained a normal karyotype after prolonged
      culture in SFM. In summary, this study demonstrates that the hESCs cultured in
      defined non-conditioned serum-free medium (NC-SFM) supplemented with growth
      factor(s) retain the characteristics and replicative potential of hESCs. The use
      of defined culture system with NC-SFM on human laminin simplifies scale-up and
      allows for reproducible generation of hESCs under defined and controlled
      conditions that would serve as a starting material for production of hESC derived
      cells for therapeutic use.

PMID- 15971229
TI  - Phenotype analysis using network motifs derived from changes in regulatory
      network dynamics.
AB  - The intrinsic dynamic response of a transcriptional regulatory network depends
      directly on molecular interactions in the cellular transcription, translation,
      and degradation machineries. These interactions can be incorporated into dynamic
      mathematical models of the biochemical system using the biophysical relationship
      with the model parameters. Modifications of such interactions bring changes to
      the biological behavior of the cells, and therefore, many normal and pathological
      cellular states depend on them. It is important for analysis, prediction,
      diagnosis, and treatment of cellular function to have an experimentally derived
      model with parameters that adequately represent the molecular interactions of
      interest. Finding the model and parameters of a transcriptional regulatory
      network is a difficult task that has been approached at different levels and with
      different techniques. We develop here a new analysis method (based on previous
      work on network inference, modeling, and parameter identification) that finds the
      most changed parameters from yeast oligonucleotide microarray expression patterns
      in cases where a phenotype difference exists between two samples. We then relate
      and examine the changed parameters with their associated genes, corresponding
      genetic functional categories, and particular subnetworks and connectivities. The
      biophysical bases for these changes are also identified by studying the
      relationship of the changed parameters with the transcription, translation, and
      degradation mechanisms. The method is improved to cases where there are two or
      more transcription factors influencing transcription, and a statistical analysis
      is performed to give a measurement of the uniqueness and robustness of the
      parameter fit.

PMID- 15971230
TI  - The 2004 Human Genome Variation Society scientific meeting.
AB  - The Human Genome Variation Society annual scientific meeting was held on 26
      October 2004 in Toronto, Canada, and attracted 85 registrants. Meeting
      participants from 14 countries reported on the recent advances and progress made
      toward the detection, analysis, and documentation of genetic variation. Reports
      were made on improvements to software that can enable curators to create mutation
      databases that are uniform and are therefore more widely used and easy to
      distribute. Other reports on software included databases to create haplotypes,
      predict pathogenic mutations, and compile information on mutations from various
      sources including relevant clinical data. Improvements to methods for the
      identification of functional SNPs were reported. New mutation detection methods
      and methods to identify the effect of a mutation on phenotype were also
      presented. This meeting report summarizes these presentations.

PMID- 15971231
TI  - Hereditary angioedema: the mutation spectrum of SERPING1/C1NH in a large Spanish
      cohort.
AB  - Hereditary angioedema (HAE) is a disease caused by defects in the C1 inhibitor
      gene (SERPING1/C1NH). We screened the entire C1NH gene for mutations in a large
      series of 87 Spanish families (77 with type I, and 10 with type II HAE) by SSCP,
      sequencing, Southern blotting, and quantitative multiplex PCR of short
      fluorescent fragments (QMPSF), and we characterized several defects at the mRNA
      level. We found large rearrangements in 13 families, and point mutations or
      microdeletions/insertions in 74 families. The 13 large rearrangements included
      nine exon deletions, of which at least eight were distinct, two were distinct
      exon duplications, and two were rearrangements whose precise nature could not be
      determined. We confirmed that exon 4 is particularly prone to rearrangements.
      Thirty-six mutations were unreported, and included 10 microdeletions/insertions,
      10 missense, five nonsense, eight splicing, and three splicing or missense
      mutations. Moreover, we detected six novel uncharacterized sequence variants
      (USV). RT-PCR studies showed that in addition to several intronic splice site
      mutations tested, the exonic mutations c.882C>G and c.884T>G, located near the 3'
      end of exon 5, also produced exon skipping. This is the first evidence of
      SERPING1/C1NH mutations in coding regions that differ from the canonical splice
      sites that affect splicing, which suggests the presence of an exonic splicing
      enhancer (ESE) in exon 5.

PMID- 15971232
TI  - A path from I(h) to C1 symmetry for C20 cage molecule.
AB  - The symmetry of the C20 cage is studied based on the intrinsical relationship
      among point groups (Bradley, C. J.; Cracknell, A. P. The Mathematical Theory of
      Symmetry in Solids; Claredon Press: Oxford, 1972). The structure of the C20 cage
      with I(h) symmetry is constructed, as are eight other structures with subgroup
      symmetry. A path from I(h) symmetry to C1 symmetry is obtained for the closed
      shell electronic state, and the structure with D2h symmetry is the most stable on
      this path. Using the D2h structure the correlation energy correction is studied
      on the condition of restricted excitation space at the CCSD(T) level. We obtain
      curves on the relation between the orbital numbers and the total energy at the
      CCSD(T), CCSD, and MP2 level, respectively. The results of these curves obtained
      from MP2 and CCSD(T) methods have the same tendency, while the results of CCSD
      gradually diverge with an increase in orbital numbers. When the orbitals used in
      the calculation reach 460, the total energy is -759.644 hartree at MP2 level and
      is -759.721 hartree by the CCSD(T) method. From the calculation results, we find
      that a large basis set can improve the reliability of the MP2 method, and to
      restrict excitation space is necessary when using the CCSD(T) method.

PMID- 15971233
TI  - Defining remission and relapse in bulimia nervosa.
AB  - OBJECTIVE: The goals of the current study were to compare the relapse rates
      obtained when definitions of both remission and relapse were systematically
      varied and to propose some consensus definitions related to relapse in bulimia
      nervosa (BN). METHOD: This was an uncontrolled, prospective follow-up study based
      on 46 women who met criteria for BN (based on criteria in the 3rd Rev. ed. of the
      Diagnostic and Statistical Manual of Mental Disorders [Washington, DC: American
      Psychiatric Association]) before treatment and were abstinent or had low
      frequency symptoms after treatment. Assessments were conducted every 3 months for
      up to 19 months. Data were analyzed with Kaplan-Meier survival analysis. RESULTS:
      Relapse rates at 19 months ranged from 21% to 55% depending on the definitions of
      remission and relapse applied. DISCUSSION: Relapse rates are strongly influenced
      by definitions of remission and relapse. We propose that partial remission,
      defined as a maximum of two symptom episodes per month for 2 months, should
      constitute eligibility for relapse and relapse should be defined as meeting full
      diagnostic criteria for 3 months.

PMID- 15971234
TI  - Describing course of illness: does our language matter?

PMID- 15971235
TI  - Disclosure patterns of eating and weight concerns to clinicians, educational
      professionals, family, and peers.
AB  - OBJECTIVE: The current study investigated disclosure of eating and weight
      concerns to professionals, peers, and family. METHOD: Responses to a telephone
      questionnaire probing disclosure patterns were analyzed in a sample of 216 adult
      subjects with eating or weight symptoms, concerns, or problems. RESULTS: Nearly
      all of the sample (97.7%) had disclosed information about eating or weight
      symptoms or concerns to someone. Only 57% of the sample had disclosed this
      information to a health care professional. However, among subjects who had not
      otherwise volunteered information about their concerns, those who were queried
      were more likely than not to disclose them to health care professionals,
      counselors, and coaches. Disclosure to a health care professional or school
      counselor was associated with a higher likelihood of subsequent treatment
      seeking. DISCUSSION: These data suggest that individuals with disordered eating
      may be quite amenable to disclosing symptoms in clinical settings. Asking about
      an eating disorder may enhance detection and facilitate treatment in clinical
      settings.

PMID- 15971236
TI  - Thulium fiber laser lithotripsy: an in vitro analysis of stone fragmentation
      using a modulated 110-watt Thulium fiber laser at 1.94 microm.
AB  - BACKGROUND AND OBJECTIVES: The high-power Thulium fiber laser has previously been
      shown to rapidly vaporize and coagulate soft urinary tissues (e.g., prostate).
      This is the first preliminary study of a high-power Thulium fiber laser for
      fragmentation of urinary stones. STUDY DESIGN/MATERIALS AND METHODS: A continuous
      wave, high-power Thulium fiber laser operating at a wavelength of 1.94 microm,
      was modulated to operate in pulsed mode with an output pulse energy of 1 J
      through a 300-microm-core silica fiber at a 20 milliseconds pulse length and
      repetition rate of 10 Hz. The fragmentation time to reduce uric acid (UA) (n =
      13) and calcium oxalate monohydrate (COM) (n = 6) stones into particles < 2 mm
      was measured. RESULTS: Mean initial mass of the UA and COM stones measured 860+/
      211 and 763 +/- 204 mg. Fragmentation rates measured 388 +/- 49 and 25 +/- 2
      mg/minute. Average time needed to fragment the UA and COM stones into particles <
      2 mm was 2.25 +/- 0.63 and 30.7 +/- 8.4 minutes, respectively. CONCLUSIONS: The
      high-power Thulium fiber laser, when operated in pulsed mode, is capable of
      fragmenting both soft (UA) and hard (COM) urinary stones. The Thulium fiber laser
      may be useful as a single laser system for use in multiple soft and hard tissue
      laser ablation applications in urology.

PMID- 15971237
TI  - Do preschool children understand what it means to "diet," and do they do it?
AB  - OBJECTIVE: The current study determined what preschool children understand about
      dieting and the extent to which they report engaging in dieting behaviors.
      METHOD: Forty-two children (mean age = 5.2 years) were interviewed about their
      understanding of the word "diet" and about food restraint behaviors. Children's
      height and weight were recorded. RESULTS: Only 17% of the children provided an
      accurate definition of the word diet (i.e., an answer having to do with the foods
      a person eats). None of the children mentioned weight loss in their definition.
      Children reported occasional use of restraint behaviors. Girls and heavier
      children reported more use of restraint. DISCUSSION: Children did not have a
      clear understanding of the word diet. Thus, the use of the word diet should be
      avoided when assessing eating behaviors in preschool children. Individual
      differences in reported dieting behaviors were in the expected directions,
      suggesting validity in these reports and early emerging social pressures to diet.

PMID- 15971238
TI  - A case-control study of family composition in anorexia nervosa.
AB  - OBJECTIVES: The family compositions of patients with anorexia nervosa may inform
      consideration of the etiology of the disorder, and previous studies in this area
      have had methodologic weaknesses which we sought to address in a case-control
      design. METHODS: The family composition of 259 females with anorexia nervosa was
      compared with that of 200 control subjects. Birth order and numbers of brothers
      and sisters were compared in unmatched and matched analyses using both univariate
      and multivariate statistical techniques. RESULTS: In both the unpaired univariate
      and the matched conditional logistic regression analyses, the anorexic females
      were both significantly later in the birth order and had significantly fewer
      brothers than control subjects. DISCUSSION: Although it is possible that these
      findings were affected by response bias among control subjects, it is more likely
      that they are informative with regard to the etiology of anorexia nervosa.
      Possible etiologic links are discussed in relation to biologic, family, and
      sociocultural factors.

PMID- 15971239
TI  - Bulimic symptoms, cognitions, and body dissatisfaction in women with major
      depressive disorder.
AB  - OBJECTIVE: The goals of this study were to assess eating disorder symptoms in
      depressed women with no history of eating disturbance and to evaluate the
      clinical significance of these symptoms relative to those reported by women with
      bulimia spectrum disorder. METHOD: Participants were 63 women with major
      depressive disorder (MDD) (n = 19), bulimia spectrum disorder (n = 20), or no
      history of MDD or eating disorder (n = 24). Measures included diagnostic
      interviews and self-report questionnaires designed to assess diagnostic criteria
      for bulimia nervosa, subthreshold eating disorder symptoms, dysfunctional
      attitudes about appearance, and body dissatisfaction. RESULTS: There were no
      significant differences between depressed and bulimic women on shape concerns,
      appearance overvaluation, or body dissatisfaction. Depressed women endorsed
      significantly more subthreshold eating disorder symptoms, dysfunctional attitudes
      about appearance, and body dissatisfaction than did control subjects. DISCUSSION:
      Eating disorder symptoms may be associated with depression in women in the
      absence of comorbid eating disorder diagnoses.

PMID- 15971240
TI  - Facial teleangectasias: our experience in treatment with IPL.
AB  - BACKGROUND AND OBJECTIVES: Facial teleangectasias can be a relevant cosmetic
      problem, which the patient usually hides with a thick layer of makeup. This study
      will describe the response on these vascular lesions using the intense pulsed
      light (IPL) source. METHODS: Five hundred eighteen consecutive patients were
      treated with Photoderm VL (Lumenis Ltd.). The average age of patients of various
      skin types (Fitzpatrick I to IV) was 48.5 years. They were subjected to a mean of
      1.69 treatments (range 1-9) followed up 48 hours, 72 hours, 1 week, 3 weeks, and
      1 month after each treatment. All patients were followed up after 2 months from
      the last treatment and the percentage of clearance was assessed by comparing pre-
      and post-treatment photographs. The patients also answered a questionnaire in
      which they expressed personal satisfaction. The physicians evaluation was also
      recorded on the same form. RESULTS: Patients (87.64%) presented a clearance of
      75%-100%. The results appear not correlated with lesions size, age, skin type but
      with operator experience. Minimal side adverse effects occurred in 20% of the
      patients. CONCLUSION: The IPL source, Photoderm VL, can be considered an
      alternative or a supplement to the existing laser devices for facial
      teleangectasias treatment.

PMID- 15971241
TI  - Media-portrayed idealized images, body shame, and appearance anxiety.
AB  - OBJECTIVE: This study was designed to determine the effects of media-portrayed
      idealized images on young women's body shame and appearance anxiety, and to
      establish whether the effects depend on advertisement type and on participant
      self-objectification. METHOD: Participants were 39 female university students.
      Twenty-four magazine advertisements comprised 12 body-related and 12 non-body
      related products, one half of each with, and the other one half without,
      idealized images. Preexposure and post exposure body shame and appearance anxiety
      measures were recorded. RESULTS: Appearance anxiety increased after viewing
      advertisements featuring idealized images. There was also a significant
      interaction between self-objectification level and idealized body (presence vs.
      absence). No differences emerged for body-related compared with non-body-related
      product advertisements. The only result for body shame was a main effect for
      time. Participants' body shame increased after exposure to idealized images,
      irrespective of advertisement type. DISCUSSION: Although our findings reveal that
      media-portrayed idealized images detrimentally affect the body image of young
      women, they highlight the individual differences in vulnerability and the
      different effects for different components of body image. These results are
      discussed in terms of their implications for the prevention and early
      intervention of body image and dieting-related disorders. (

PMID- 15971242
TI  - State dissociation in bulimic eating disorders: an experimental study.
AB  - BACKGROUND: Dissociation and binge eating appear to have equivalent functions,
      lowering awareness of generalized threat and negative self-esteem. Dissociation
      can be a general characteristic of the individual, present in all situations
      (i.e., a trait), or it can be a time-limited reaction to a specific situation
      (i.e., a state). Previous studies have shown that the subliminal presentation of
      threat cues leads to increased bulimic behaviors. This experimental study
      examines whether dissociation is activated under similar conditions, thus testing
      whether dissociation is a reactive state in bulimic women, as well as a trait.
      METHOD: The participants were 24 bulimic and 26 nonclinical women, each of whom
      completed the Eating Disorders Inventory and the Dissociative Experiences Scale.
      Each woman was exposed to subliminal neutral and threat cues, before completing
      the subjective component of the Clinician-Administered Dissociation Scale and a
      measure of anxiety and mood (the Hospital Anxiety and Depression Scale). RESULTS:
      The subliminal threat cue significantly increased state dissociation
      (particularly derealization levels) in the bulimic women but had no effect on the
      nonclinical group. There was no impact on mood. DISCUSSION: State dissociation
      appears to play an integral role in the bulimic process, but further studies are
      needed to determine the causal structure in that relationship and whether it
      applies in other disorders. Future clinical practice should be directed towards
      the identification and treatment of state dissociation in therapy.

PMID- 15971243
TI  - Illusory correlation for body type and happiness: covariation bias and its
      relationship to eating disorder symptoms.
AB  - OBJECTIVE: The current study investigates covariation bias (illusory correlation)
      in the perceived association between happiness and body type, as well as the
      association between covariation bias and eating disorder symptoms. METHOD:
      Undergraduate women (n = 186) rated pictures of women on a variety of attributes,
      including happiness, degree of overweight, and attractiveness. Later, they were
      asked to judge the level of covariation between these attributes that was present
      in the stimuli that they had rated. Participants also completed the Eating
      Disorder Examination-Self-Report Questionnaire (EDE-Q). RESULTS: Participants
      reported that there was a negative association between weight and happiness in
      the stimuli that they had rated, even though the true correlation in the data was
      zero. This covariation bias was stronger among participants with higher levels of
      eating disorder symptoms. DISCUSSION: The results suggest a cognitive bias that
      may play a role in maintaining and enhancing concerns about shape and weight in
      symptomatic women.

PMID- 15971244
TI  - The impact of caloric preloading on attempts at food and eating-related thought
      suppression in restrained and unrestrained eaters.
AB  - OBJECTIVE: The current study examined the impact of dietary restraint and caloric
      preload on thought suppression in a sample of 64 college females classified as
      either restrained or unrestrained eaters. METHOD: Participants engaged in a 60
      min laboratory session. One half of the participants were preloaded with a high
      calorie milkshake and all participants were randomly assigned to a food and
      eating-related thought suppression condition or a no suppression control
      condition. Food-related thoughts were assessed with a digital counter and verbal
      references to food were tracked with an audio recorder. RESULTS: Restrained
      participants instructed to suppress food-related thoughts demonstrated
      significantly more food and eating-related thoughts than unrestrained
      participants. Preloading was associated with an increase in the frequency of
      indirect mentions to food and eating. DISCUSSION: Although the hypothesized
      "rebound" effect did not occur for any study groups, these findings indicate that
      both restraint status and preloading impact food and eating-related thoughts.

PMID- 15971246
TI  - Results of nonablative wrinkle reduction with a 1,450-nm diode laser:
      difficulties in the assessment of "subtle changes".
AB  - BACKGROUND AND OBJECTIVE: Nonablative resurfacing has proven its efficacy in
      vascular and pigmented lesions, while its capacity of substantial wrinkle
      reduction is still discussed controversially. We present the treatment results of
      a 1,450 nm diode laser for facial rhytides. METHODS: Thirty facial regions were
      treated with a 1,450 nm diode laser. Pre- and post treatment pictures were
      compared by the treating physician and two blinded observers. RESULTS: Even if
      mild improvement was rated in up to 35% of the post treatment pictures, a
      discrepancy shows up in the assessments of the three observers, presenting almost
      no congruency in the rating of improvement. CONCLUSIONS: Our study failed to
      provide convincing data on the efficacy of nonablative treatment of rhytides with
      the 1,450 nm diode laser. In this respect, we challenge objective judgment in the
      assessment of subtle changes in nonablative wrinkle reduction.

PMID- 15971245
TI  - Epidermal and vascular damage analysis of in vivo human skin in response to 595
      nm pulsed laser irradiation.
AB  - BACKGROUND AND OBJECTIVES: Laser irradiation is the current modality for
      treatment of cutaneous hypervascular malformations such as port wine stains and
      telangiectasia. Although cryogen spray cooling (CSC) is used to protect the
      epidermis from non-specific laser-induced thermal damage in moderately-pigmented
      skin types, individuals with high melanin content are still at risk for epidermal
      damage using the current laser irradiation and CSC parameters. The objective of
      this study was to investigate the influence of the spray Weber number (1,100 or
      5,100) on epidermal protection and examine vascular coagulation in response to
      pulsed dye laser irradiation. STUDY DESIGN/MATERIALS AND METHODS: Normal, in vivo
      human skin from eight subjects of Fitzpatrick skin types I-V were precooled with
      either low or high Weber number cryogen sprays and subsequently irradiated with a
      pulsed dye laser at 595 nm. Analysis of gross purpura, morphological vascular
      damage, and apoptosis of the vascular walls were performed. RESULTS: Results
      demonstrated a high Weber number spray of 5,100 decreased the level of epidermal
      damage in darker and moderate pigmented individuals compared to a Weber number
      spray of 1,100. This study also established a positive correlation between gross
      purpura and the level of vessel wall apoptosis. CONCLUSIONS: This study has
      demonstrated that CSC with a high Weber number spray can decrease nonspecific
      thermal damage to the epidermis in response to laser irradiation in vivo. We have
      also established a positive correlation between gross purpura and the level of
      vessel wall apoptosis. Lasers Surg. Med. (c) 2005 Wiley-Liss, Inc.

PMID- 15971247
TI  - Marked ascites and serum carbohydrate antigen (CA) 125 elevation in a patient
      with anorexia nervosa.
AB  - These findings suggest, for psychiatrically hospitalized adolescent females, that
      different patterns of factors may contribute to the maintenance of eating and
      body image disturbances across ethnic groups. Future research testing models of
      the etiology or maintenance of these disturbances needs to include ethnicity to
      ascertain whether the hypothesized components operate differently by ethnicity.

PMID- 15971248
TI  - Fluid Intake in patients with eating disorders.
AB  - OBJECTIVES: The current study examined the fluid intake of patients with eating
      disorders and factors that may influence the amount and type of fluid consumed.
      Subjects comprised 81 inpatients with eating disorders. METHODS: A 7-day semi
      standardized, retrospective fluid history was taken by a dietitian when the
      subjects were admitted to an eating disorder unit. Total fluid consumed per day
      was measured, which included all energy-free, energy-containing, and caffeine
      containing fluids (all in milliliters per kilogram). Age, body mass index (BMI),
      and eating disorder behaviors (purging, binge eating, and excessive exercise)
      were also evaluated. RESULTS: Fluid intakes ranged from 250 ml to >6 L per day,
      with an average of 2.7 L. Only 17% of patients had fluid intakes in the
      recommended range. The most commonly consumed beverage was water followed by diet
      cola, coffee, juice, and tea. The lower the BMI and the older the patient, the
      greater the fluid intake. CONCLUSIONS: Fluid intake is variable and should be
      part of the clinical assessment of the eating disorder patient.

PMID- 15971249
TI  - Core beliefs and the presence or absence of eating disorder symptoms and
      depressive symptoms in adolescent girls.
AB  - OBJECTIVE: Core beliefs specific to eating disorder and depressive symptoms were
      investigated in four groups of adolescent girls well matched on these symptoms.
      METHOD: A total of 272 girls were included and two measures of core beliefs were
      compared. The measures were the Young Schema Questionnaire (YSQ) and the Negative
      Self-Beliefs subscale of the Eating Disorder Belief Questionnaire (EDBQ).
      RESULTS: One-way analyses of variance found that both measures distinguished a
      "healthy" group and a group high on depressed symptoms, but not one high on
      eating disorder symptoms. Both measures also distinguished the unhealthy group
      from a high eating disorder symptom group, but only the EDBQ subscale
      distinguished this group from the group high on depressive symptoms. Discriminant
      function analysis indicated that both measures identified beliefs specific to
      depression but only the EDBQ subscale was able to identify beliefs specific to
      eating disorder symptoms. These beliefs were I'm stupid and I'm ugly. DISCUSSION:
      In an analogue population at least, the EDBQ negative self-beliefs subscale may
      be a more sensitive measure of eating disorder related core beliefs than the YSQ.
      The practical difficulties of replicating the current study in a clinical
      population are discussed, and a next step is proposed for future research on this
      topic.

PMID- 15971250
TI  - Ethnic differences in the prediction of eating and body image disturbances among
      female adolescent psychiatric inpatients.
AB  - OBJECTIVE: The current study examined predictors of eating and body image
      disturbances in psychiatrically hospitalized female adolescents and investigated
      whether the predictors differ by ethnicity. METHOD: Participants were 427 (320
      Caucasian, 53 Latina, 54 African American) female adolescent psychiatric
      inpatients. Predictors of eating disorder features (dietary restraint, binge
      eating, and purging) and body image dissatisfaction (BID) were tested separately
      for the three ethnic groups. In addition to the eating and BID variables, the
      following predictor variables were considered: depression, anxiety, impulsivity,
      negative self-esteem, peer insecurity, and abuse. RESULTS: Caucasians reported
      significantly higher levels of dietary restraint and BID than Latinas and African
      Americans, whereas reports of binge eating did not differ by ethnicity.
      Regression analyses revealed that the predictor variables accounted for
      significant and substantial amounts of the variance in the four eating and body
      image domains. Different psychological and social variables predicted eating
      disorder symptoms and BID across ethnic groups. DISCUSSION: These findings
      suggest, for psychiatrically hospitalized adolescent females, that different
      patterns of factors may contribute to the maintenance of eating and body image
      disturbances across ethnic groups. Future research testing models of the etiology
      or maintenance of these disturbances needs to include ethnicity to ascertain
      whether the hypothesized components operate differently by ethnicity.

PMID- 15971251
TI  - The expression pattern of MUC1 glycoforms and other biomarkers of endometrial
      receptivity in fertile and infertile women.
AB  - Changes in the surface epithelium of the endometrium, characterized in part by
      alterations in cell-surface molecules, sex steroid receptors and the appearance
      of pinopodes, coincide with the window of endometrial receptivity in the
      menstrual cycle. This study was performed to evaluate the usefulness of
      hematoxylin and eosin staining, scanning and transmission microscopy, and MUC1
      glycoform, sex steroid receptor, and interleukin receptor (type 1) expression as
      biomarkers of endometrial receptivity using carefully characterized clinical
      fertile and infertile groups of women. Using a combination of
      immunohistochemistry and scanning electron microscopy (SEM) called scanning
      immunoelectron microscopy (SIM), we confirmed that MUC1 mucin was not associated
      with the endometrial pinopodes, which have been linked with embryo adhesion. We
      also showed that failure of embryo implantation was associated with an abnormal
      endometrial expression of MUC1 mucin, and retention of nuclear progesterone
      receptor (PR) particularly in epithelial cells. Hematoxylin and eosin staining,
      transmission electron microscopy (TEM), SEM in isolation and immunohistochemistry
      for interleukin receptor were not shown to be useful markers. Progesterone
      dependent regulation of MUC1 appears to be an important factor in determining
      endometrial receptivity.

PMID- 15971252
TI  - Engaging teachers in an eating disorder preventive intervention.
AB  - OBJECTIVE: This study evaluated the effectiveness at 1-year follow-up of a
      psychoeducational eating disorders preventive intervention implemented by
      specifically trained teachers. METHOD: Participating teachers participated in a 5
      week training program. One hundred forty-one female students attending nine
      classes at a vocational training school in Mestre (Venice) were assessed via a
      structured clinical interview (Structured Clinical Interview for DSM-IV Axis I
      disorders) and via the 40-item Eating Attitudes Test (EAT-40). Three classes were
      randomly selected to participate in a 6-week prevention program conducted by the
      trained teachers. RESULTS: Our data show that a disturbing number of the girls
      who were asymptomatic at baseline had developed a full or partial eating disorder
      1 year later. This was the case for 2 (5%) participants and 10 (11%) subjects in
      the control group. Subjects in the prevention group differed significantly from
      the control group at the 1-year follow-up. This was the case for their EAT
      Bulimia subscale scores, which showed a significant improvement. The intervention
      group also revealed a lower development of food restraint and pathologic body
      attitudes. DISCUSSION: Given the sample size, our findings must be considered
      cautiously. However, they suggest that students can benefit from participation in
      a preventive intervention program conducted by teachers, and the benefits appear
      to be particularly pronounced for bulimic symptoms.

PMID- 15971253
TI  - Efficiency of gene transfection into donor cells for nuclear transfer of bovine
      embryos.
AB  - The production of transgenic (TG) animals by somatic cell nuclear transfer (SCNT)
      has proven to be a more efficient method than other methods, such as gene
      injection or sperm mediation. The present study was intended to evaluate the
      efficiency of gene transfection by Effectene (Qiagen, Inc.), a lipid-based
      reagent compared to electroporation in fetal-derived fibroblast cells (FFC),
      cumulus-derived fibroblast cells (CFC), and adult ear skin-derived fibroblast
      cells (AEFC). Parameters compared were factors such as chromosome abnormality,
      gene expression, and the incidence of apoptosis. Further, the TG embryos with
      transfected donor cells generated by electroporation or Effectene were compared
      to IVF and SCNT embryos in terms of rates of cleavage, blastocyst formation, and
      blastocyst cell number. Most of the cells (>80%) at confluence were at G0/G1 and
      considered to be suitable nuclear donors for cloning. Transfection with a plasmid
      containing the enhanced green fluorescent protein (pEGFP-N1) gene into FFC did
      not increase the incidence of chromosomal abnormalities. The rates of apoptosis
      in different cell types transfected with pEGFP-N1 were 3.3%-5.0%, and the values
      did not differ among groups. In addition, the rates of apoptosis in various cells
      between 5-7 and 20-22 cell passages did not differ. However, the efficiency of
      gene transfecton into FFC by Effectene reagent (14.2 +/- 1.7) was significantly
      (P < 0.05) higher than that obtained by electroporation (5.1 +/- 1.0). Among
      various cell types, the efficiency of gene transfection by Effectene and
      eletroporation of FFC (14.2 +/- 1.7 and 5.1 +/- 1.0, respectively) was
      significantly (P < 0.05) higher than transfection of CFC and AEFC by either
      method (9.4 +/- 1.5 and 3.3 +/- 0.8, 8.8 +/- 0.7, and 2.1 +/- 0.4, respectively).
      In TG embryos produced by SCNT with electroporation and Effectene, the rates of
      cleavage and blastocyst formation were significantly lower (P < 0.05) than those
      of IVF controls, but rates did not differ between SCNT and TG embryos. Similarly,
      significantly higher (P < 0.05) total cell numbers in day-8 blastocysts were
      observed in IVF controls than those in SCNT and TG embryos, but did not differ
      between SCNT and TG (136 vs. approximately 110, respectively). The results
      demonstrated that, though there were no difference in the rates of chromosomal
      aneuploidy and the incidence of apoptosis among various cell types, transfected
      with or without pEGFP-N1, FFC were the cell type most effectively transfected and
      Effectene was a suitable agent for transfection.

PMID- 15971254
TI  - Using genomewide mutagenesis screens to identify the genes required for neural
      tube closure in the mouse.
AB  - BACKGROUND: Neural tube closure is a critical embryological process that requires
      the coordination of many molecular and cellular events. Only recently has the
      molecular basis of the cell movements that drive neural tube closure begun to be
      elucidated. This has been accomplished in part due to the analysis of a growing
      number of genetically targeted and naturally occurring mouse mutant strains that
      have neural tube defects (NTDs). Currently there are more than 100 genes that
      when mutated result in NTDs in the mouse. Yet only approximately 10% of genes in
      the mouse genome have been mutated and their gross phenotype analyzed, suggesting
      that only a small percentage of the genes that can cause NTDs have been
      identified. METHODS: In order to more systematically and fully understand the
      genetic basis of neural tube closure and to begin to define the molecular
      pathways that direct this key embryonic event, our laboratories have undertaken a
      forward genetic screen in mice. From this we hope to gain a better understanding
      of the regulation of this complex morphogenic processes. CONCLUSIONS: The mouse
      provides a good model for human neural tube closure, and therefore the
      information gained from generating novel mouse models of NTDs will help to
      predict the genes responsible for human NTDs and provide experimental evidence
      for how they function.

PMID- 15971256
TI  - Influence of DNA repair gene polymorphisms on the yield of chromosomal
      aberrations.
AB  - We evaluated the influence of several DNA repair gene polymorphisms on the
      frequency of chromosomal aberrations (CAs) analyzed in peripheral lymphocytes,
      using the fluorescence in situ hybridization technique. The CA data were obtained
      from an earlier study of 84 healthy nonsmokers (48 women and 36 men) carefully
      characterized for indoor radon exposure. The frequency of translocations showed a
      wide interindividual variability, which was only partly explained by age. To
      investigate the potential role of DNA repair polymorphisms in this variation,
      genotypes of DNA repair genes OGG1 (codon 326), XPD (codon 751), XRCC1 (X-ray
      repair cross-complementing group 1) (codons 194, 280, and 399), and XRCC3 (X-ray
      repair cross-complementing group 3) (codon 241) were determined from leukocyte
      DNA using polymerase chain reaction-based methods. Negative binomial regression
      models were applied to evaluate the effect of the polymorphisms and other factors
      (age, gender, radon exposure, and medical exposure) on the frequency of CAs. No
      interactions between genotypes and radon, medical exposure, or gender were found.
      Carriers of the XRCC1 codon 280His variant allele had a two-fold increase
      (frequency ratio [FR] = 2.01, 95% confidence interval [CI] = 1.01-3.98; P =
      0.046) in unstable exchanges (dicentrics and ring chromosomes). In addition, the
      XRCC3 codon 241 homozygous variant genotype (Met/Met) was associated with an
      increase (FR = 1.70, 95% CI = 1.06-2.74; P = 0.028) in two-way translocations
      when age was taken into account in the analysis. Our data suggest that the XRCC1
      280His and XRCC3 241Met alleles affect individual CA levels, most probably via
      influencing the DNA repair phenotype.

PMID- 15971258
TI  - Micronucleated erythrocyte frequencies in old and new world primates: measurement
      of micronucleated erythrocyte frequencies in peripheral blood of Callithrix
      jacchus as a model for evaluating genotoxicity in primates.
AB  - Nonhuman primates are of particular relevance in evaluating the potential
      toxicity of drugs and environmental agents. We have used previously published
      information and data from the present study to establish a relationship for New
      World (NW) and Old World (OW) primates on the basis of the frequency of
      spontaneous micronucleated erythrocytes (MNEs) observed in peripheral blood. Data
      on spontaneous MNEs in peripheral blood from 15 species of primates, including
      humans, indicate that NW primates have significantly (P < 0.01) higher MNE
      frequencies (group mean, 9.5 +/- 7.3 MNEs/10,000 erythrocytes; range, 0.7
      20.5/10,000 erythrocytes) than OW primates (group mean, 1.0 +/- 0.9 MNEs/10,000
      erythrocytes; range, 0.0-2.6 MNEs/10,000 erythrocytes). Humans are believed to
      have developed in the OW, and human MNE frequencies were similar to those
      described for OW primate species. We selected the common marmoset (Callithrix
      jacchus), a NW primate, to determine whether therapeutic pediatric doses of
      Metotrexate (MTX; 2.5 mg/kg), Cyclophosphamide (CP; 5 mg/kg), Cytosine
      arabinoside (Ara-C; 3 mg/kg), or 5-Fluorouracil (5-FU; 10 mg/kg), administered
      daily for two consecutive days, increase the frequency of micronuclei.
      Micronucleated polychromatic erythrocyte frequencies were increased significantly
      in groups receiving MTX, CP and Ara-C, while MNE frequencies were increased by
      the Ara-C treatment. The results of this study indicate that NW primates have
      higher spontaneous MNE frequencies than OW primates, and because of this, NW
      primates like the common marmoset, may be suitable for evaluating the
      genotoxicity of chemical agents.

PMID- 15971260
TI  - Holoprosencephaly with microphthalmia, hypoplastic ears, vertebral segmentation
      defects, and congenital heart defects.

PMID- 15971261
TI  - van den Ende-Gupta syndrome of blepharophimosis, arachnodactyly, and congenital
      contractures.
AB  - Here, we report on a Venezuelan child with manifestations of van den Ende-Gupta
      syndrome, including blepharophimosis, arachnodactyly, and congenital
      contractures. We also review cases from the literature.

PMID- 15971262
TI  - A newly recognized syndrome of cutis aplasia, lipomatous footpads, microcephaly,
      hypotelorism, and, variably, single maxillary central incisor, and
      holoprosencephaly.

PMID- 15971263
TI  - Trichomegaly in two sisters with synophrys in the older sibling.

PMID- 15971264
TI  - General anesthetics attenuate gap junction coupling in P19 cell line.
AB  - Gap junction communication is widespread throughout the mammalian nervous system
      among neurons as well as glia. We addressed the hypothesis that general
      anesthetics attenuate gap junction mediated coupling in P19 cell line that can
      differentiate into neuronal-like cells and astrocytes and oligodendrocytes. We
      characterized the extent of dye coupling over time in the P19 cell line using
      colocalization of chlormethylbenzamido-1,1 dioctadecyl-3,3,3',3'
      tetramethylindocarbocyamine (CM-DiI) and calcein-AM in donor and recipient cells
      in cocultures. After seeding, the gap junction permeant dye calcein spreads from
      donor to recipient cells. CM-DiI and calcein fluorescence identified donor and
      recipient cells, respectively. The extent of intercellular connections was
      evaluated using cell counting and flow cytometry up to 2 hr after treatment.
      Clinically relevant concentrations of the intravenous anesthetics propofol (15
      microM) and thiopental (10 microM) attenuated gap junction permeability in P19
      cell cultures. In contrast, halothane, a volatile anesthetic in a concentration
      (0.64 mM) relevant to its free aqueous EC50 had no effect on gap junction
      coupling; however, very high halothane concentrations (2.8 mM) blocked dye
      transfer by approximately 90%. The results indicate that halothane concentrations
      pertinent to clinical anesthesia were unable to attenuate gap junction
      communication in a cell line that can express neuronal and glial gap junction
      proteins; however, clinically relevant concentrations of propofol and thiopental
      depressed gap junction coupling.

PMID- 15971265
TI  - Morphology of the pharyngeal cavity, especially the surface ultrastructure of
      gill arches and gill rakers in relation to the feeding ecology of the catfish
      Rita rita (Siluriformes, Bagridae).
AB  - Gill arches and the gill rakers of a sluggish, carnivorous catfish, Rita rita,
      show significant differences of their surface ultrastructure, which are
      recognized adaptive modifications in relation to food and feeding ecology of
      fish. Gill rakers on the first and second pairs of gill arches are borne on the
      oral side and are long and stout at the epi-ceratobranchial union. Gill rakers on
      the third and fourth pairs of gill arches, in contrast, are borne on the oral and
      aboral sides and are relatively delicate and short. Long and stout gill rakers on
      the first and second pairs of gill arches are considered primarily to prevent
      entry of undesirably large food items into the pharynx. Two types of taste buds,
      Type I and Type II, occur on the gill arches and the gill rakers. The raised
      taste buds, located at the apical ends of the gill rakers on the third, fourth,
      and the fifth pairs of gill arches could increase gustatory efficiency in the
      pharynx. Differences in the distribution of taste buds on the pharyngeal sides of
      different gill arches indicate that the posterior part of the pharynx plays a
      more crucial role in gustation than does the anterior part. Co-occurrence of
      teeth and taste buds on the epi- and hypopharyngeal bones denotes that food
      processing and gustation occur simultaneously in the pharynx. Villiform and
      caniform teeth on the epi- and hypopharyngeal bones are associated with a complex
      food-processing cycle. Mucous secretions, oozing through mucous cell openings,
      provide lubrication facilitating smooth passage of food through the pharynx. The
      angle of curvature at the epi-ceratobranchial union of the first to fourth pairs
      of gill arches could assist the ventral drag of ceratobranchials in lowering of
      the pharyngeal floor, thus resulting in a great expansion of the pharynx, as
      needed to accommodate the large quantities of food captured.

PMID- 15971266
TI  - Where does gonadal sex differentiation begin? Gradient of histological sex
      differentiation in the gonads of pejerrey, Odontesthes bonariensis (Pisces,
      Atherinidae).
AB  - This study investigated the possibility that the histological process of gonadal
      sex differentiation in pejerrey (Odontesthes bonariensis), a fish with marked
      temperature-dependent sex determination (TSD), occurs through a predictable
      gradient of differentiation as opposed to simultaneous or random differentiation
      throughout the gonad. For this purpose, fish reared at 17 degrees, 24 degrees,
      and 29 degrees C from hatching were sampled weekly for 11 weeks, fixed, and
      prepared for histological observation of serial cross-sections of the gonads. The
      thermal manipulation and sampling procedure ensured the availability of males and
      females at various degrees of gonadal sex differentiation. The location of the
      differentiated area(s) was estimated in the right and left gonads of 17 females
      and 14 males selected among the available specimens so as to represent increasing
      degrees of differentiation. The analysis revealed that sex differentiation
      followed a gradient from the anterior to posterior areas of the gonads regardless
      of sex. Furthermore, plotting of the degree of sex differentiation in the right
      gonad as a function of the degree of differentiation of the left gonad clearly
      showed that sex differentiation only begins in the right gonad when 10-30% of the
      length of the left gonad has already differentiated. The mean rostral edge of the
      differentiated areas in females was 9% and 10.8% for the left and right gonads,
      respectively, while for males these values were 7.3% and 7.0%, respectively.
      Thus, it was established that ovarian and testicular differentiation in pejerrey
      follow both a cephalocaudal and a left-to-right gradient. Possible explanations
      for this gradient and its relevance for TSD in pejerrey, that is, as a mechanism
      to prevent discrepant differentiation of male and female features within the same
      gonad, are discussed.

PMID- 15971267
TI  - Genome size and endonuclear DNA replication in spiders.
AB  - Although genome sizes (C-values) are now available for 115 arachnid species
      (Gregory and Shorthouse [2003] J Hered 94:285-290), the extent of genome
      amplification (endonuclear DNA replication or polyploidization) accompanying
      tissue differentiation in this diverse and abundant class of invertebrates
      remains unknown. To explore this aspect of arachnid development, samples of
      hemolymph and other tissues were taken from wild-caught specimens as air-dried
      smears, stained with the Feulgen reaction for DNA, and assayed using both
      scanning and image analysis densitometry. Cells from midgut diverticula and
      Malpighian tubules of Argiope and Lycosa (=Pardosa) often showed giant nuclei
      with 50-100 pg of DNA per nucleus, reflecting at least four cycles of endonuclear
      DNA replication when compared to the DNA content of hemocytes or sperm from the
      same specimen. Nuclei with markedly elevated DNA levels also appeared, but far
      less frequently, in tissue samples from several other arachnid species
      (Antrodiaetus, Hypochilus, Latrodectus, Liphistus and Loxosceles), but revealed
      no correlation with differences in somatic cell (2C) genome sizes. Our data show
      that several DNA classes of polysomatic nuclei regularly arise during tissue
      differentiation in some species of spiders and may provide an interesting model
      system for further study of patterns of tissue-specific variation in DNA
      endoreduplication during development.

PMID- 15971268
TI  - Different levels of ovine interferon-tau gene expressions are regulated through
      the short promoter region including Ets-2 binding site.
AB  - Regulation of interferon-tau (IFNtau) production, a conceptus secretory protein
      implicated in the process of maternal recognition of pregnancy, has not been
      fully elucidated. Among more than 10 ovine IFNtau (oIFNtau) gene sequences
      characterized, approximately 75% of oIFNtau transcripts expressed in utero is
      derived from oIFNtau-o10 gene and amounts of transcripts from other oIFNtau genes
      such as oIFNtau-o8 or oIFNtau-o2 are minimal. It was hypothesized that the
      variation in expression levels exhibited by oIFNtau-o10 and oIFNtau-o8/-o2 genes
      was due to differences in the proximal promoter regions of these oIFNtau genes.
      To test this hypothesis, transient transfection experiments with human
      choriocarcinoma JEG3 cells were executed with deleted and/or mutated 5'-upstream
      regions of these oIFNtau genes attached to the chloramphenicol acetyltransferase
      (CAT) reporter gene. Because only the Ets-2 binding site located in the oIFNtau
      o10 gene appeared to differentiate the expression levels of these constructs, the
      6 base pair (bp) Ets-2 sequence from the oIFNtau-o10 gene inserted into the
      oIFNtau-o8/-o2 gene-reporter construct was examined. The insertion of this Ets-2
      binding site into the oIFNtau-o8/o2-reporter construct failed to increase the
      degree of transactivation. Rather than this 6 bp sequence, a 22 bp sequence of
      the proximal promoter region, including the Ets-2 binding site, of the oIFNtau
      o10 gene was required for oIFNtau-o8/-o2-reporter transactivation. By
      electrophoretic mobility shift assay (EMSA), nuclear protein(s) bound to this 22
      bp from the oIFNtau-o10 and oIFNtau-o8/o2 genes differed. These results suggest
      that the short promoter region including the Ets-2 binding site, not the Ets-2
      binding region itself, may determine different levels of oIFNtau gene expressions
      seen in utero.

PMID- 15971269
TI  - Reduced p38 mitogen-activated protein kinase in donor grafts accelerates acute
      intestinal graft-versus-host disease in mice.
AB  - The gastrointestinal tract is a major target of graft-versus-host disease (GVHD),
      which constitutes a life-threatening complication of bone marrow transplantation.
      GVHD is mainly caused by the activation of donor-derived lymphocytes, in which
      cytokine cascades play essential roles. Since p38 MAPK (p38) has been identified
      as a regulator of cytokine reactions and proposed as a molecular target for anti
      inflammatory therapy, we investigated the contribution of p38 to the severity of
      murine intestinal GVHD. Unexpectedly, p38alpha(+/-) donor graft induced more
      acute GVHD-related mortality and more severe gut injury. The survival of
      p38alpha(+/-) donor-derived intestinal intraepithelial lymphocytes (IEL) was
      prolonged in vitro and in vivo, and TNF-alpha expression in the p38alpha(+/-)
      donor-derived IEL was also increased compared with wild-type cells. In contrast,
      the p38alpha(+/-) grafted mice resulted in decreased expansion of donor
      lymphocytes in mesenteric lymph nodes, and the up-regulation of IL-12p40 and IL
      18 was diminished. These findings suggest that p38 has dichotomous effects for
      inflammatory response in vivo; not only regulates inflammatory cytokine
      expression and lymphocyte expansion, but also has distinct regulatory functions
      for IEL in intestinal GVHD. In conclusion, the inhibition of p38 may not be a
      suitable anti-inflammatory strategy for GVHD due to the associated intestinal
      injury.

PMID- 15971270
TI  - Controlling complement resistance in cancer by using human monoclonal antibodies
      that neutralize complement-regulatory proteins CD55 and CD59.
AB  - Expression of the complement-regulatory proteins (CRP) CD46, CD55 and CD59
      represents a strategy used by tumor cells to evade complement-dependent cell
      cytoxicity stimulated by monoclonal antibodies. We have isolated two single-chain
      variable fragments (scFv) to CD55 and CD59 from a human phage-display library and
      from these scFv we have produced two miniantibodies (MB), MB-55 (against CD55)
      and MB-59 (against CD59), containing the human hinge-CH2-CH3 domains of IgG1. The
      specificity of the two MB for the corresponding CRP was assessed by ELISA using
      purified CD46, CD55 and CD59. MB-55 and MB-59 neutralized the inhibitory activity
      of CD55 and CD59, respectively, restoring the complement-mediated lysis of sheep
      and guinea pig erythrocytes that was otherwise inhibited by the two CRP. FACS
      analysis revealed binding of MB-55 and MB-59 to the lymphoma cell line Karpas
      422. The two MB induced a two-fold increase in the complement-dependent killing
      of these cells stimulated by Rituximab, a chimeric anti-CD20 monoclonal antibody.
      Transfection of HEK293T cells with vectors encoding MB-55 or MB-59 markedly
      reduced the expression of CD55 and CD59. We conclude that the human antibodies MB
      55 and MB-59 may represent a therapeutic tool to increase the complement
      dependent killing activity of Rituximab in the treatment of non-Hodgkin's
      lymphoma.

PMID- 15971271
TI  - Selection of CMV-specific CD8+ and CD4+ T cells by mini-EBV-transformed B cell
      lines.
AB  - Efficient protocols to generate cytomegalovirus (CMV)-specific T cells are
      required for adoptive immunotherapy. Recombinant Epstein-Barr virus (EBV) vectors
      called mini-EBV can be used to establish permanent B cell lines in a single step,
      which present the CMV antigen pp65 in a constitutive manner. These B cell lines,
      coined pp65 mini-LCL, were successfully used to reactivate and expand CMV
      specific cytotoxic T cells. Here we evaluate this pp65 mini-EBV system in closer
      detail, focusing on (1) the quantification of T cells with specific effector
      function and (2) the identification of CMV-specific CD4(+) helper T cells. The co
      expansion of various functional CMV epitope specificities was demonstrated by IFN
      gamma enzyme-linked immunospot assay (ELISPOT) assays and HLA-peptide tetramer
      staining. Single-cell cloning resulted in both CD4(+) and CD8(+) T cell clones,
      the majority of which was CMV specific. Thus, mini-LCL present the pp65 antigen
      on HLA class I and II, mobilizing both arms of the T cell response. Using a
      peptide library covering the pp65 sequence for further analysis of T cell clones,
      we identified new pp65 CD8(+) and CD4(+) T cell epitopes.

PMID- 15971272
TI  - Expression of lymphocyte activation gene 3 (LAG-3) on B cells is induced by T
      cells.
AB  - Lymphocyte activation gene 3 (LAG-3/CD223) is a CD4 homolog known to be
      selectively expressed in activated T and NK cells. It is thought to have a
      negative regulatory function in T cells. With the help of new monoclonal
      antibodies against mouse LAG-3, we show that LAG-3 surface expression is not
      limited to activated T and NK cells but is also found on activated B cells.
      Induction of B cell surface expression is T cell dependent and mediated by a
      soluble factor. The majority of LAG-3 on B cell surface is endogenously produced,
      even though soluble LAG-3 is present in the culture supernatants and can be
      passively absorbed. As B cells express LAG-3 in a T cell dependent manner and not
      when activated by Toll-like-receptor agonists alone, we propose LAG-3 as a new
      marker of T cell induced B cell activation.

PMID- 15971273
TI  - The human antibody repertoire specific for rabies virus glycoprotein as selected
      from immune libraries.
AB  - Antibody phage display technology was used to identify human monoclonal
      antibodies that neutralize rabies virus (RV). A phage repertoire was constructed
      using antibody genes harvested from the blood of vaccinated donors. Selections
      using this repertoire and three different antigen formats of the RV glycoprotein
      (gp) resulted in the identification of 147 unique antibody fragments specific for
      the RV gp. Analysis of the DNA sequences of these antibodies demonstrated a large
      variation in the heavy- and light-chain germ-line gene usage, suggesting that a
      broad antibody repertoire was selected. The single-chain variable fragment (scFv)
      antibodies were tested in vitro for RV neutralization, resulting in 39
      specificities that neutralize the virus. Of the scFv clones, 21 were converted
      into full-length human IgG(1) format. Analysis of viral escape variants and
      binding competition experiments indicated that the majority of the neutralizing
      antibodies are directed against antigenic site III of the RV gp. The obtained
      specificities expand the set of human anti-RV antibodies eligible for inclusion
      in an antibody cocktail aimed for use in rabies post-exposure prophylaxis.

PMID- 15971274
TI  - Identification of a third evolutionarily conserved gene within the RAG locus and
      its RAG1-dependent and -independent regulation.
AB  - Recombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific
      endonucleases indispensable for rearrangements of antigen-receptor gene segments
      but also capable of causing deleterious chromosome rearrangements. The mechanisms
      regulating RAG expression and repression are not clear. Here we identify NWC, a
      third evolutionarily conserved gene within the RAG locus, and show that it is
      ubiquitously expressed, with the notable exception of RAG-nonexpressing immature
      and mature T and B lymphocytes because in lymphocytes it is regulated by the RAG1
      promoter and transcribed as RAG1-NWC hybrid mRNA molecules. We also show that in
      all other cells NWC is controlled by the RAG2 intragenic promoter, which in
      immature and mature T and B lymphocytes is silent. The possible implications of
      these findings for understanding the activation and inactivation of RAG genes in
      lymphocytes and their repression in other cells are discussed.

PMID- 15971275
TI  - A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I
      safety and immunogenicity.
AB  - Nicotine is the principal addictive component in tobacco, and following uptake
      acts in the central nervous system. The smoking-cessation efforts of most smokers
      fail because a single slip often delivers sufficient nicotine to the brain to
      reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain
      by induction of specific antibodies may be an effective means to prevent such
      relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by
      the coat protein of the bacteriophage Qb. In preclinical experiments, this
      Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After
      intravenous nicotine challenge, vaccinated mice exhibited strongly reduced
      nicotine levels in the brain compared with control mice. In a phase I study, 32
      healthy non-smokers were immunized with NicQb. The vaccine was safe and well
      tolerated. All volunteers who received NicQb showed nicotine-specific IgM
      antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody
      levels could be boosted by a second injection or the addition of Alum as an
      adjuvant and the antibodies had a high affinity for nicotine. These data suggest
      that antibodies induced by NicQb may prevent relapses by sequestering nicotine in
      the blood of immunized smokers.

PMID- 15971276
TI  - A B220+ CD117+ CD19- hematopoietic progenitor with potent lymphoid and myeloid
      developmental potential.
AB  - In this report, we identify in the bone marrow (BM) of normal mice a
      subpopulation of B220+ CD117+ CD19- NK1.1- cells with potent lymphoid and myeloid
      developmental potential. These cells represent 0.1-0.2% of nucleated BM cells. By
      limiting dilution analysis in the presence of the appropriate combination of
      stromal cells and cytokines, 1 in 5-10 sorted cells formed B cells, 1 in 10-15
      formed T cells and 1 in 5-10 generated macrophages. When cultured on a mixture of
      OP9 stroma and OP9 stromal cells expressing the Notch ligand Delta-like-1, single
      cells generated both T and B cells. Following intravenous infusion, freshly
      sorted cells transiently reconstituted both the T and B cell progenitor
      compartments, generating cohorts of mature T and B lymphocytes. The relationship
      between B220+ CD117+ CD19- NK1.1- cells of wild-type mice and other multi-lineage
      BM progenitors is discussed.

PMID- 15971277
TI  - Unraveling the origin of lymphocyte progenitors.
AB  - Lymphocytes are ultimately derived from hematopoietic stem cells, however the
      intervening steps that give rise to lymphocyte progenitors are still under
      intense investigation. In particular, whether a common lymphocyte progenitor
      serves exclusively as a lymphoid precursor, or whether this cell retains limited
      myeloid progenitor potential are addressed by Rolink and colleagues. This issue
      is highlighted by their identification within the bone marrow of early
      progenitors with lymphoid and myeloid developmental potential or EPLMs. How these
      cells fit into our current understanding of lymphocyte development, and how this
      new subset helps to further refine our view of the common lymphocyte progenitor
      are discussed.

PMID- 15971278
TI  - Mass spectrometric and quantum-chemical study on the structure, stability, and
      chirality of protonated serine dimers.
AB  - Stability and structure of homo- and heterochiral protonated serine (Ser) dimers
      were investigated by a combination of mass spectrometry and ab initio quantum
      chemical calculations. This established that the energy difference between the
      most stable homo- and heterochiral forms is very small: tandem mass spectrometry
      with Cooks' kinetic method yielded a negligible difference in Gibbs free energy
      (0.2+/-0.2 kJ mol(-1)). The various isomeric forms of (Ser)2 H+ and their
      energetics were determined by extensive electronic-structure calculations, which
      yielded homo- and heterochiral forms of the isomers with distinctly different
      relative energies. The most stable homochiral isomer is stabilized by two
      hydrogen bonds and is far more stable than any other homochiral isomer. The most
      stable heterochiral isomer has completely different features, and it is
      characterized by a salt-bridge structure. This clearly shows that salt-bridge
      structures do exist in the gas phase even in comparatively small molecules and in
      the absence of particularly basic or acidic functional groups.

PMID- 15971279
TI  - Illustrating the power of singlet oxygen chemistry in a synthetic context:
      biomimetic syntheses of litseaverticillols A-G, I and J and the structural
      reassignment of litseaverticillol E.
AB  - Biomimetic syntheses of the litseaverticillols A-G, I and J are reported herein.
      The syntheses rely heavily on the application of two different modes of reaction
      for photochemically generated singlet oxygen, namely, the [4+2] cycloaddition of
      singlet oxygen (1O2) with furans and the ene reaction of 1O2 with double bonds.
      The highlight of these syntheses is a one-pot cascade sequence, involving five
      synthetic operations initiated by a [4+2] reaction, to form the fully
      functionalised litseaverticillol core. A series of regioselective ene reactions
      are then used to appositely functionalise the side chains. The synthesis of
      litseaverticillol E (both its originally proposed and its actual structures)
      allows a structural reassignment of this natural product.

PMID- 15971280
TI  - Complete atrioventricular block diagnosed prenatally: anything new on the block?

PMID- 15971281
TI  - Antenatal diagnosis of placenta accreta: a review.
AB  - The incidence of placenta accreta should rise steadily over the next century as
      the frequency of Cesarean sections and advanced maternal age, both independent
      risk factors, increases. Patients who are at risk should be identified before an
      ultrasound examination and the characteristic findings searched for. In the first
      trimester, these include a low-lying sac that appears to be attached to the
      anterior wall of the uterus. As early as 16 weeks irregular vascular sinuses
      appear, which have turbulent flow within. The bladder wall may appear interrupted
      or have small bulges of the placenta into the bladder space. Absence of the
      normal echolucent space between the placenta and myometrium is not a reliable
      sign by itself, since this space may be absent in normal patients with an
      anterior placenta. Color Doppler will show that some of the placental sinuses
      traverse the uterine wall. Magnetic resonance imaging has not yet been shown to
      aid in the diagnosis, but in the future, with improvement of resolution and
      shortened sequences, it should be particularly useful in identifying the patients
      that have placenta percreta.

PMID- 15971282
TI  - Prenatal ultrasonographic appearance of isolated cutis verticis gyrata.

PMID- 15971283
TI  - Three-dimensional sonographic diagnosis of ovarian pregnancy.

PMID- 15971284
TI  - Standardization of power Doppler quantification of blood flow in the human fetus
      using the aorta and inferior vena cava.
AB  - OBJECTIVE: This study aimed to test the applicability to the fetus of
      mathematical techniques developed to standardize power Doppler indices of adult
      regional perfusion. METHOD: Fetal power Doppler imaging was performed on 14
      fetuses (25-37 weeks' gestation) using a standardized parasagittal plane,
      examining renal and aortic blood flow, and additionally inferior vena caval (IVC)
      flow in one fetus. Images were stored and transferred for off-line computer
      analysis using purpose-designed software. We first tested the need for techniques
      to remove the effects of red blood cell clumping on power Doppler amplitude, then
      performed further analyses to: (1) investigate cardiac cycle effects on aortic
      amplitude; (2) determine the spatial consistency of, and influence of angle of
      insonation on, maximal pixel value; (3) quantify temporal consistency; and (4)
      compare peak pixel values in the fetal aorta and IVC. RESULTS: No rouleaux effect
      on the vascular profile was detectable, in contrast to that identified in the
      adult. Within each fetus a consistent value was seen in the center of the aorta
      corresponding to 100% vascular amplitude, which was unaltered by the phase of the
      cardiac cycle, with a coefficient of variation of 28.9% at 89 degrees and 6.5% at
      73 degrees . This value was constant in the aorta and IVC. CONCLUSION: Fetal
      blood does not appear to form rouleaux to any significant degree, so there is no
      artificially elevated maximal value for power Doppler amplitude as seen in the
      adult. We propose that the value representing 100% amplitude may be consistently
      measured in the center of large fetal vessels such as the aorta, allowing the
      direct measurement of fractional moving blood volumes in the human fetus.

PMID- 15971285
TI  - Increased latency of absent end-diastolic flow in the umbilical artery of
      monochorionic twin fetuses.
AB  - OBJECTIVE: To determine if absent end-diastolic flow (AEDF) in the umbilical
      artery (UA) has a longer latency in monochorionic (MC) twin fetuses compared to
      singleton or dichorionic twin (DC) fetuses. METHODS: One hundred and eight
      pregnancies with a fetus with AEDF were reviewed: 47 MC and 17 DC twin
      pregnancies and 44 singletons. Because twin-twin transfusion syndrome (TTTS) is a
      potential confounder when determining latency, subgroup analysis was also
      performed on the 21 MC affected pregnancies without TTTS. Latency of AEDF (in
      days) was defined as the difference between the gestational age at diagnosis of
      AEDF and gestational age at delivery or intrauterine death. RESULTS: Latency was
      similar in MC twins (median, 39 days) and DC twins (30 days) but longer compared
      to singletons (11 days; P = 0.0001). After excluding pregnancies with TTTS,
      latency in non-TTTS MC twins (54 days) was longer than in both singletons and DC
      twins. This was due to an earlier gestational age at AEDF in non-TTTS MC twins of
      20 weeks compared to 27 weeks in both singleton and DC twins because median
      gestational age at delivery was similar in MC twins, DC twins and singletons.
      CONCLUSIONS: The latency period of UA AEDF is longer in MC twins than in
      singletons. Our data suggest that in MC twin fetuses without TTTS, AEDF begins
      earlier and lasts about twice as long as in DC twin fetuses, which is consistent
      with placental insufficiency not being the sole factor mediating abnormal UA
      waveforms in MC placentation. This observation is important in counseling and
      managing twin pregnancies discordant for AEDF.

PMID- 15971286
TI  - Simple method for the assay of clindamycin in human plasma by reversed-phase high
      performance liquid chromatography with UV detector.
AB  - A rapid and simple high-performance liquid chromatography (HPLC) method was
      developed and validated for the quantification of clindamycin in human plasma.
      After precipitation with 50% trichloroacetic acid (TCA) containing the internal
      standard, propranolol, the analysis of the clindamycin level in the plasma
      samples was carried out using a reverse-phase cyano (CN) column with ultraviolet
      detection (204 nm). The chromatographic separation was accomplished with an
      isocratic mobile phase consisting of acetonitrile-distilled water-7.6 mm
      tetramethylammonium chloride (TMA) (60:40:0.075, v/v/v), adjusted to pH 3.2. The
      proposed method was specific and sensitive with a lower limit of quantitation
      (LLOQ) of 0.2 microg/mL. This HPLC method was validated by examining the
      precision and accuracy for inter- and intraday analysis in the concentration
      range 0.2-20.0 microg/mL. The relative standard deviations (RSD) in the inter-
      and intraday validation were 6.1-14.9 and 6.0-16.1%, respectively. In the
      stability test, clindamycin was found to be stable in human plasma during the
      storage and assay procedure. The present HPLC method was applied to the analysis
      of samples taken up to 12 h after a single oral administration of clindamycin in
      healthy volunteers.

PMID- 15971287
TI  - Diagnosis of fetal ductus arteriosus aneurysm: importance of the three-vessel
      view.
AB  - OBJECTIVE: To present four cases of ductus arteriosus aneurysm (DAA) detected by
      fetal echocardiography and highlight the value of the three-vessel view in the
      diagnosis of DAA. METHODS: In addition to the standard fetal echocardiographic
      views, we examined the three-vessel view in four cases of DAA. The three-vessel
      view was achieved by sliding the transducer cranially from the four-chamber plane
      toward the fetal upper mediastinum to demonstrate cross-sections of the main
      pulmonary artery, the ascending aorta and superior vena cava arranged in a
      straight line from the left anterior to the right posterior aspect of the
      mediastinum. DAA was diagnosed when there was a tortuous ductus arteriosus with a
      dilation that protruded leftward of the aortic arch. CASE SERIES: In the first
      case, an insulin-dependent diabetic woman underwent fetal ultrasound examination
      at 36 weeks' gestation showing right-to-left cardiac disproportion and
      bidirectional flow in the aorta and main pulmonary artery (PA). The three-vessel
      view showed a dilated ductus arteriosus (DA) which was stenosed at its distal
      end. In the second case, a woman had fetal ultrasound scans at 38 and 39 weeks'
      gestation for suspected intrauterine growth restriction and oligohydramnios. The
      scans identified an abnormal aortic arch and the three-vessel view showed an
      elongated vascular structure at the distal end of the PA, which was the DAA. In
      the third case, a woman with a high-risk obstetric history had multiple scans
      showing an abnormal PA to aorta relationship, with an apparent 'kink' in the PA.
      The three-vessel view clarified that this was the DAA. In the fourth case, a
      woman was scanned because of a 3-kg weight gain in 1 week. The fetal ultrasound
      scan showed moderate polyhydramnios with normal fetal growth and normal
      intracardiac anatomy and flow, and the three-vessel view demonstrated a large DA.
      In each of these cases, the DAA appeared to have occurred in isolation with non
      specific clinical findings. CONCLUSION: We advocate the use of the three-vessel
      view, in conjunction with the standard echocardiography views currently employed,
      to assist in the diagnosis of DAA.

PMID- 15971288
TI  - Development of an HPLC-fluorescence determination method for carboxylic acids
      related to the tricarboxylic acid cycle as a metabolome tool.
AB  - We report the simultaneous determination of the carboxylic acids related to the
      tricarboxylic acid (TCA) cycle, which plays an important role in producing
      adenosine triphosphate (ATP) and generating energy in mitochondria. Seven
      carboxylic acids from the TCA cycle, and pyruvic acid and 2-methylsuccinic acid,
      as an internal standard, were derivatized with a fluorescent reagent for carboxyl
      groups, 4-N,N-dimethylaminosulfonyl-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ),
      in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and 4-N,N
      dimethyaminopyridine as the coupling reagents, at 60 degrees C for 120 min.
      Subsequently, the excess DBD-PZ was removed efficiently using a cation-exchange
      cartridge, SDB-RPS (Empore). These fluorescent derivatives were separated well
      from each other on an octadecyl silica column (TSKgel ODS-80Ts, 250 x 4.6 mm,
      i.d.) with an eluent of acetonitrile-water containing 1% formic acid at a flow
      rate of 0.8 mL/min, and were detected fluorometrically at 560 nm, with excitation
      at 450 nm. The validation data were satisfactory in the range of 2.5-100 microm
      citric acid, isocitric acid, 2-oxoglutaric acid, succinic acid and fumaric acid.
      The detection limit (S/N = 3) for citric acid was 2 fmol on the column. The
      structures of these derivatives were confirmed by high-performance liquid
      chromatography-mass spectrometry, which proved that their carboxylic groups were
      completely labeled with DBD-PZ, except for oxaloacetic acid. This HPLC method was
      successfully applied to the analysis of TCA cycle metabolites in rat urine. The
      method will also be useful for metabolome research, such as for target analyses
      of metabolites with carboxyl groups, not only in urine but also in cells and
      organs.

PMID- 15971289
TI  - Simultaneous determination of six HIV protease inhibitors (amprenavir, indinavir,
      lopinavir, nelfinavir, ritonavir and saquinavir), the active metabolite of
      nelfinavir (M8) and non-nucleoside reverse transcriptase inhibitor (efavirenz) in
      human plasma by high-performance liquid chromatography.
AB  - We report the development of a simple, economical and reliable chromatographic
      method for the simultaneous determination of six HIV protease inhibitors (PIs;
      amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir), the
      active metabolite of nelfinavir (M8) and the non-nucleoside reverse transcriptase
      inhibitor (NNRTI; efavirenz) in human plasma. After extraction from plasma with
      an ethyl acetate-acetonitrile mixture, the analytes were separated on a phenyl
      column with a gradient of acetonitrile and phosphate solutions, and detected at
      three ultraviolet wavelengths. Calibration curves were linear over the range
      0.025-15 microg/mL for saquinavir and 0.05-15 microg/mL for the other analytes.
      The accuracies ranged from -6.9% to +7.6%, and the intra-assay and inter-assay
      precisions were <9.2 and <11.8%, respectively. Our method, covering most of the
      PIs and NNRTIs currently used, facilitates ready therapeutic drug monitoring in
      hospital laboratories.

PMID- 15971290
TI  - Mechanism of the formation of a dehydrated ion by an unusual loss of oxygen at
      the 4'-carbonyl group of abscisic acid methyl ester in electron ionization mass
      spectrometry.
AB  - Methyl ester of abscisic acid (ABA), a plant hormone, gives a dehydrated ion at
      m/z 260 in electron ionization mass spectrometry (EI-MS). This dehydrated ion had
      been considered to be derived only from the elimination of the tertiary hydroxyl
      group at C-1'. We found that 34% of the dehydrated ion was formed by elimination
      of the oxygen atom at the 4'-carbonyl group, and the remaining 66% by elimination
      of the 1'-hydroxyl group. This unusual elimination of the carbonyl oxygen was
      shown with [4'-(18)O]ABA methyl ester. Involvement of the 4'-carbonyl oxygen in
      dehydration was observed in methyl ester of phaseic acid (PA), a natural
      metabolite of ABA, but not in 1'-deoxy-ABA methyl ester or isophorone. This
      suggested that the 1'-hydroxyl group was necessary for the elimination of the 4'
      carbonyl oxygen. ABA methyl esters labeled with stable isotopes showed that
      hydrogen atoms at the 1'-hydroxyl group and at C-4 or -5 or -3' or - 5' or -7'
      were eliminated with the 4'-carbonyl oxygen. These results allow us to propose a
      formation mechanism of the dehydrated ion derived from the elimination of 4'
      carbonyl oxygen and hydrogen atoms at C-4 and 1'-oxygen in ABA methyl ester as
      follows: first, ionization at the 1'-hydroxyl group occurs to give an ion
      radical, and the proton at the 1'-oxygen migrates to the 4'-carbonyl oxygen after
      the bond fission between C-1'-C-6'; second, migration of the proton at C-4 to the
      1'-oxygen is followed by migration of the protons at C-5 and C-7' to C-4 and C-5,
      respectively; finally, the proton at the 1'-oxygen migrates to the 4'-hydroxyl
      group, and H(2)O at C-4' is eliminated to give the dehydrated ion. Our findings
      point out that a dehydrated ion is not always derived from the elimination of a
      hydroxyl group.

PMID- 15971291
TI  - Profiling isoflavone conjugates in root extracts of lupine species with
      LC/ESI/MSn systems.
AB  - Extracts obtained from roots of three lupine species (Lupinus albus, L.
      angustifolius, L. luteus) were analysed using LC/UV and LC/ESI/MS(n). The
      experiments were performed using two mass spectrometric systems, equipped with
      the triple quadrupole or ion trap analysers. Thirteen to twenty isomeric
      isoflavone conjugates were identified in roots of the investigated lupine
      species. These were di- and monoglycosides of genistein and 2'-hydroxygenistein
      with different patterns of glycosylation, both at oxygen and carbon atoms; some
      glycosides were acylated with malonic acid. It was not possible to establish the
      glycosylation sites of the aglycone only on the basis of the registered mass
      spectra; however, it was possible to differentiate C- and O-glucosides of
      isoflavones. Only comparison of retention times with those of standard compounds
      permitted to indicate the correct glycosylation pattern. In the case of
      diglycosides, the glycosylation pattern (O-diglucoside or O-glucosylglucoside)
      was distinguishable on the basis of the relative intensities of daughter ions in
      the mass spectra of protonated molecular ions. It was not possible to elucidate
      the site of malonylation on the sugar moiety from mass spectra, however,
      protonated molecules [M + H](+) of isoflavone glucosides with different placement
      of the malonyl group on the sugar ring were recognized in the extracts. In
      addition to the isoflavone glycosides, some flavone or flavonol glycosides were
      identified in the samples on the basis of collision-induced daughter ion spectra
      of the aglycone ions. A comparison of results obtained with the triple quadrupole
      and ion trap analysers was done in the course of the investigations.

PMID- 15971292
TI  - DISQ 1: high maternal AFP and normal scan.

PMID- 15971293
TI  - MALDI-TOF mass spectrometric analysis for the characterization of the 5,10,15,20
      tetrakis- (m-hydroxyphenyl)bacteriochlorin (m-THPBC) photoproducts in biological
      environment.
AB  - Photoproducts formation upon irradiation (739 nm) of 5,10,15,20-tetrakis(m
      hydroxyphenyl)bacteriochlorin (m-THPBC) in phosphate buffer saline (PBS)
      supplemented with human serum albumin (HSA) were studied by means of absorption
      spectroscopy and MALDI-TOF mass spectrometry. The experiments were performed with
      a freshly prepared PBS-HSA solution of m-THPBC and with a PBS-HSA m-THPBC
      solution incubated for 6 h at 37 degrees C. The incubation of m-THPBC solution
      leads to the dye monomerisation, whereas in the freshly prepared solution, m
      THPBC is under an aggregated form. Regardless of the incubation condition,
      photobleaching experiments carried out by absorption spectroscopy demonstrate the
      degradation of the photosensitizer and its phototransformation in m-THPC.
      Moreover, m-THPC was the sole photoproduct detected using absorption
      spectroscopy. Together with a degradation of m-THPBC and formation of m-THPC,
      MALDI-TOF mass spectrometry evidenced several other photoinduced modifications.
      Photoproducts such as dihydroxy m-THPBC and dihydroxy m-THPC were detected in
      both conditions; however, the formation of hydroxylated photoproducts was
      significantly greater in incubated solution. In addition, small molecules arising
      from the degradation of the photosensitizer and identified as dipyrin derivatives
      and dipyrrolic synthon were observed.

PMID- 15971294
TI  - Formation and stability of oxocarbenium ions from glycosides.
AB  - Structural, protecting group and leaving group effects in the formation of
      oxocarbenium intermediates were studied in the gas phase. It is found that
      significant stabilization of oxocarbenium cations is achieved by protecting
      groups that interact with the cationic center via neighboring group participation
      despite the electron-withdrawing character of these moieties. On the other hand,
      ethereal protecting groups do not facilitate the formation of oxocarbenium
      intermediates. The experimental findings are supported by DFT calculations that
      show the following order of stabilization by the group adjacent to the cationic
      center: RCO > SiR(3) > R, where R is an alkyl group. This indicates that the SN1
      like mechanism that is commonly proposed for this reaction is not always valid.
      Moderate leaving group effect is also detected in a series of thioaryl
      glucopyranosides.

PMID- 15971295
TI  - Isomerization of the protonated acetone dimer in the gas phase.
AB  - Mass spectrometry-based methods have been employed in order to study the
      reactions of non- (h(6)/h(6)), half (d(6)/h(6)), and fully (d(6)/d(6)) deuterium
      labeled protonated dimers of acetone in the gas phase. Neither kinetic nor
      thermodynamic isotope effects were found. From MIKES experiments (both
      spontaneous and collision-induced dissociations), it was found that the relative
      ion yield (m/z 65 vs m/z 59) from the dissociation reaction of half deuterium
      labeled (d(6)/h(6)) protonated dimer of acetone is dependent on the internal
      energy. A relative ion yield (m/z 65 vs m/z 59) close to unity is observed for
      cold, nonactivated, metastable ions, whereas the ion yield is observed to
      increase (favoring m/z 65) when the pressure of the collision gas is increased.
      This is in striking contrast to what would be expected if a kinetic isotope
      effect were present. A combined study of the kinetics and the thermodynamics of
      the association reaction between acetone and protonated acetone implicates the
      presence of at least two isomeric adducts. We have employed G3(MP2) theory to map
      the potential energy surface leading from the reactants, acetone and protonated
      acetone, to the various isomeric adducts. The proton-bound dimer of acetone was
      found to be the lowest-energy isomer, and protonated diacetone alcohol the next
      lowest-energy isomer. Protonated diacetone alcohol, even though it is an isomer
      hidden behind many barriers, can possibly account for the observed relative ion
      yield and its dependence on the mode of activation.

PMID- 15971297
TI  - Craving nicotine: It's in the genes.

PMID- 15971296
TI  - Does quantitative analysis of three-dimensional power Doppler angiography have a
      role in the diagnosis of malignant pelvic solid tumors? A preliminary study.
AB  - OBJECTIVE: To investigate the role of a simplified method for the three
      dimensional (3D) quantification of tumor vascularity in the differential
      diagnosis of solid pelvic masses. METHODS: Twenty-four patients with a solid
      pelvic mass on B-mode ultrasound evaluation underwent 3D power Doppler evaluation
      before surgery. The volume of interest was obtained by drawing the largest
      section of the mass in three orthogonal planes. The following 3D vascular
      parameters were calculated for all patients: relative color, average color and
      flow measure. Receiver-operating characteristics curve analysis was used to
      choose the best cut-off value. The overall agreement between the test result and
      the actual outcome was calculated using kappa statistics. RESULTS: Fifteen of 24
      subjects were found to have pelvic malignancy. The relative color and the flow
      measure were significantly higher in malignant (9.7 (8.98) and 8.95 (8.78)
      (median (interquartile range (IQR)), respectively) than in benign masses (2
      (4.42) and 1.79 (4.71), respectively; P < 0.05) but there was no difference in
      the average color. The best cut-off values of relative color and flow measure
      were 3.2 and 2.8, respectively. The use of relative color showed a sensitivity of
      80% with a specificity of 67% with an overall agreement that was higher, though
      only marginally so, than that of qualitative 3D power Doppler (kappa = 0.47 and
      0.44, respectively). CONCLUSIONS: In a small group of pelvic masses that appear
      malignant on B-mode ultrasonography, the use of 3D quantification of tumor
      vascularity yields a diagnostic accuracy that is similar to that of subjective
      evaluation of vascularity. We suspect, however, that the quantitative method will
      produce more consistent results between operators.

PMID- 15971298
TI  - The two sides of PEPFAR in Uganda.

PMID- 15971299
TI  - Sweden's state pharmacies may lose hold over drug sales.

PMID- 15971300
TI  - Hadrontherapy with carbon12: radiotherapy of the near future.

PMID- 15971301
TI  - Radiobiological rationale and patient selection for high-LET radiation in cancer
      therapy.
AB  - The rationale for introducing ion beams in cancer therapy is the high level of
      physical selectivity that can be achieved with ions, equal or even better than
      with proton beams or modern photon techniques, as well as the potential advantage
      of high-LET radiations for some tumour types and sites. The radiobiological
      arguments for high-LET radiation in cancer therapy are reviewed: reduction of OER
      in the case of hypoxic and poorly-reoxygenating tumours, and the lesser
      importance of repair phenomena which are a problem in controlling repair
      proficient photon-resistant tumours. Fast neutrons were the first type of high
      LET radiation used clinically, and were often applied under suboptimal technical
      conditions. Nevertheless, useful clinical information was derived from the
      neutron experience. A greater benefit from neutrons than from conventional
      radiotherapy was found for several tumour sites. The present discussion is
      limited to the results for salivary gland tumours and prostatic adenocarcinoma.
      Based on the fast neutron experience, radiobiological arguments, and the added
      benefit of excellent physical selectivity of ion beams, the potential clinical
      indications for high-LET ions are discussed: hypoxic, slowly growing and well
      differentiated photon-resistant tumours. One of the main remaining issues is the
      selection of individual patients for high- or low-LET radiation. Since the
      physical selectivity of ions now matches that obtained with other techniques, the
      selection of patients will be based only on the radiobiological characteristics
      of the tumour.

PMID- 15971302
TI  - A networking for patient recruitment: the experience of choroidal melanoma.
AB  - The organization of a networking for patient recruitment is a main concern for a
      new facility using charged particles. The experience of choroidal melanoma in
      Nice demonstrates the possibility to create "de novo" a protontherapy center
      treating a sufficient number of patients. The influence of the opening of new
      facilities is analyzed.

PMID- 15971303
TI  - Medical aspects of the National Centre For Oncological Hadrontherapy (CNAO-Centro
      Nazionale Adroterapia Oncologica) in Italy.
AB  - More than 20 hadrontherapy centres are active in the world and about 40,000
      patients have been treated, almost 4000 with ions. Physical selectivity and high
      relative biologic efficiency (RBE) represent the rationale for using ions in the
      treatment of tumours. The clinical results are very promising and justify the
      construction of new centres. We present the main characteristics of CNAO (Centro
      Nazionale Adroterapia Oncologica) and its possible integration in a nationwide
      network. The Italian project started in 1991 thanks to the activity of the TERA
      Foundation and was financed by the Italian Government in 2002. The CNAO will be
      built in Pavia to start clinical activity in 2007. The equipment will include a
      synchrotron and 3 treatment rooms mainly devoted to carbon ions but able to
      deliver also protons. The Centre should be able to deliver up to 20,000 fractions
      / year. The realization of CNAO is part of a more ambitious project to set up an
      integrated national network. The need of hadrontherapy centres is defined by
      epidemiological studies based on Italian tumour registries showing that almost
      900 patients can be electively treated with protontherapy and about 10,000 could
      be included in clinical trials. Considering that ions could be used for
      radioresistant tumours that affect about 25,000 new patients/year, we estimate
      that 10-15%, i.e. 3000-4000 patients would benefit from ion therapy. The
      realization of a nationwide network possibly linked to a larger European network
      will be very helpful in making available hadrontherapy for a large part of the
      population.

PMID- 15971304
TI  - Epidemiological aspects of hadron therapy: a prospective nationwide study of the
      Austrian project MedAustron and the Austrian Society of Radiooncology (OEGRO).
AB  - BACKGROUND: The planned MedAustron hadron therapy facility is designed to compare
      proton and carbon ion beam therapy under the same technical conditions. For the
      calculation of the number of potential patients for hadron therapy so far, only
      epidemiological estimations on cancer incidence are available without inclusion
      of the percentage of patients routinely referred to conventional radiotherapy.
      MATERIALS AND METHODS: Nationwide prospective survey to collect disease and
      treatment related data on patients receiving conventional radiotherapy at all 12
      treatment facilities. Epidemiological cancer incidence (Statistic Austria 1999)
      were correlated with the number of patients receiving conventional radiotherapy.
      Based on published clinical and experimental results on proton and carbon ion
      therapy, a calculation of patient's subgroups suitable for hadron therapy was
      performed at five European University hospitals involved in the HICAT, CNAO,
      ETOILE and MEDAustron project. Using the mean values of the University specific
      percentages per tumour site, the number of potential patients was estimated.
      RESULTS: In Austria, a total of 3783 patients started radiotherapy during the
      study period of 3 months resulting in an approximated number of 15132 patients
      per year. The number of potential patients was estimated to 2044 per year,
      representing 5.6% of all newly diagnosed cancer patients and 13.5% of all
      irradiated cancer patients. CONCLUSION: There is a clear place for a hadron
      therapy facility in Austria, based on pattern of care in radiotherapy, cancer
      incidence and indications.

PMID- 15971305
TI  - The med AUSTRON/OGRO patterns of care study on radiotherapy indications in
      Austria.
AB  - PURPOSE: In Austria a national survey was conducted by Med
      AUSTRON/Osterreichische Gesellschaft for Radio--Onkologie, Radiobiologie und
      Medizinische Radiophysik (OGRO) in order to estimate the indications, patient
      numbers and radiotherapy treatment planning procedures and performances at all
      Austrian radiotherapy institutes. Results were correlated with incidence rates
      (Austrian cancer registry) to determine patterns of radiotherapy practice in
      Austria. MATERIAL AND METHODS: At 12 radiotherapy departments of Austria data of
      all patients receiving irradiation within a 3 months (2002/2003) period were
      assessed. On the basis of a questionnaire number of treated patients,
      indications, and parameters of disease (stage, histology) and treatment
      modalities were evaluated. Results were analysed with regard to different tumour
      groups, according to academic and non academic hospitals, and correlated with
      epidemiological data on cancer incidence. RESULTS: In total, 3783 patients were
      registered within this period. According to the different tumour entities
      percentages of patients receiving radiotherapy within initial treatment varied
      from 3% to 90 % (e.g. brain tumours: 77%, breast cancer: 90%, prostate cancer:
      35%). The most frequent indications to radiotherapy per radiotherapy department
      were breast cancer (range 22%-35%; mean 26%), urological tumours (range 6%-27%;
      mean 12%) and bone metastases (mean 10%, range 3%-17%). CONCLUSION: In Austria
      breast cancer, urological tumours and bone metastases are representing the most
      common indications to radiotherapy. Among the different departments variations in
      indications to radiotherapy were observed. Our study is the first evaluation of
      radiotherapeutic management in Austria.

PMID- 15971306
TI  - Protons versus photons: a status assessment at the beginning of the 21st Century.
AB  - At present modern photon delivery techniques permit high dose isodose
      conformality similar to protons in many cases. However, a proton advantage
      appears to still be present for target volumes of higher degrees of complexity
      and concavity. Also, for selected histologies and sites, notably skull base
      tumors, protons have established a "gold standard" and photon data have yet to
      duplicate those proton results in clinical practice. Proton radiation therapy
      offers superior dose distribution by reduced low-dose integral irradiated volume.
      The avoidance of functional and cosmetic side effects in children by protons is
      at present acknowledged by the radiation oncology community and is expected to
      gain similar recognition in adult patients. This advantage of protons and
      disadvantage for photons constitutes an "inherent physical gap" that will likely
      be long lasting. Although the priorities of proton irradiation advantages have
      shifted over the decades, clinical advantages remain and are of sufficient
      significance and importance to justify further development and installation of
      proton radiation facilities worldwide.

PMID- 15971307
TI  - Status of the clinical work at Hyogo.
AB  - On April 1, 2001, the Hyogo Ion Beam Medical Center (HIBMC) was opened as the
      first facility in the world to provide ion beam therapy using 2 types of beams,
      protons and carbon-ions. We will introduce the HIBMC, and report the results of
      the clinical study and general practice.

PMID- 15971309
TI  - Clinical complementarities between proton and carbon therapies.
AB  - Protons are characterised by low LET, but compared with photons and electrons
      have an improved physical depth dose distribution. Some indications for protons,
      i.e., ocular melanoma, chordoma and chondrosarcoma of the base of skull or
      cervical spine, are now accepted by the radiation oncology community as the
      treatment of choice. Others are still under evaluation, e.g. meningioma, locally
      advanced nasopharynx tumours, paediatric tumours. Neutrons have the biological
      advantage of a high LET, but their distribution of dose is in most cases
      suboptimal. Despite this, there are radiobiological arguments leading to expect
      that neutrons might be of some benefit in patients with tumours that are
      resistant to photons, slowly growing or containing a high proportion of hypoxic
      cells. There is some clinical evidence or rationale for a potential high LET
      advantage for locally extensive (I think that the current (jargon) word is
      extended in English..) salivary gland tumours, locally extensive(extended)
      prostate carcinoma, slowly growing inoperable soft tissue sarcoma,
      adenocarcinoma, adenoid cystic carcinoma of the paranasal sinuses, melanoma and
      rectal carcinoma. Light ions combine the high LET advantage of neutrons and the
      improved physical depth dose distribution of protons. The opportunity offered by
      an optimised distribution of dose should open a new era for high-LET particles,
      especially in deeply situated x-ray resistant tumours, where the use of neutron
      beams was restricted by the low quality of their depth-dose profiles. Preliminary
      results are encouraging.

PMID- 15971308
TI  - Overview of clinical experiences on carbon ion radiotherapy at NIRS.
AB  - BACKGROUND AND PURPOSE: Carbon ion beams provide physical and biological
      advantages over photons. This study summarizes the experiences of carbon ion
      radiotherapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the
      National Institute of Radiological Sciences. MATERIALS AND METHODS: Between June
      1994 and August 2003, a total of 1601 patients with various types of malignant
      tumors were enrolled in phase I/II dose-escalation studies and clinical phase II
      studies. All but malignant glioma patients received carbon ion radiotherapy alone
      with a fraction number and overall treatment time being fixed for each tumor
      site, given to one field per day and 3 or 4 days per week. In dose-escalation
      studies, the total dose was escalated by 5 or 10% increments to ensure a safe
      patient treatment and to determine appropriate dose levels. RESULTS: In the
      initial dose-escalation studies, severe late complications of the recto-sigmoid
      colon and esophagus were observed in those patients who received high dose levels
      for prostate, uterine cervix and esophageal cancer. Such adverse effects,
      however, did shortly disappear as a result of determining safe dose levels and
      because of improvements in the irradiation method. Carbon ion radiotherapy has
      shown improvement of outcome for tumor entities: (a) locally advanced head and
      neck tumors, in particular those with non-squamous cell histology including
      adenocarcinoma, adenoid cystic carcinoma, and malignant melanoma; (b) early stage
      NSCLC and locally advanced NSCLC; (c) locally advanced bone and soft tissue
      sarcomas not suited for surgical resection; (d) locally advanced hepatocellular
      carcinomas; (e) locally advanced prostate carcinomas, in particular for high-risk
      patients; (f) chordoma and chondrosarcoma of the skull base and cervical spine,
      and (g) post-operative pelvic recurrence of rectal cancer. Treatment of malignant
      gliomas, pancreatic, uterine cervix, and esophageal cancer is being investigated
      within dose-escalation studies. There is a rationale for the use of short-course
      RT regimen due to the superior dose localization and the unique biological
      properties of high-LET beams. This has been proven in treatment of NSCLC and
      hepatoma, where the fraction number has been successfully reduced to 4-12
      fractions delivered within 1-3 weeks. Even for other types of tumors including
      prostate cancer, bone/soft tissue sarcoma and head/neck tumors, it was equally
      possible to apply the therapy in much shorter treatment times as compared to
      conventional RT regimen. CONCLUSION: Carbon ion radiotherapy, due to its physical
      and biologic advantages over photons, has provided improved outcome in terms of
      minimized toxicity and high local control rates for locally advanced tumors and
      pathologically non-squamous cell type of tumors. Using carbon ion radiotherapy,
      hypofractionated radiotherapy with application of larger doses per fraction and a
      reduction of overall treatment times as compared to conventional radiotherapy was
      enabled.

PMID- 15971310
TI  - Carbon ion radiation therapy for chordomas and low grade chondrosarcomas--current
      status of the clinical trials at GSI.
AB  - Carbon ion radiation therapy (RT) is available at the German Ion Research Center
      (GSI) in Darmstadt, Germany, since December 1997. Patient treatments within the
      pilot project are carried out by radiation oncologists of the University of
      Heidelberg in cooperation with the Department of Biophysics of GSI, the Division
      of Medical Physics of the German Cancer Research Center Heidelberg and the
      Research Center Rossendorf. Patients are treated within three beam time blocks of
      20 days per year at the basic physics research center at GSI, the overall
      capacity per year being 45 to 50 patients. Main purpose of the pilot project was
      to investigate carbon ion radiation therapy for different tumor entities within
      clinical phase I/II trials. This manuscript updates the results of the clinical
      phase I/II trial of carbon ion RT in chordomas and low grade chondrosarcomas of
      the skull base and summarizes the current status of the ongoing phase I/II trial
      for extracranial chordomas and low grade chondrosarcomas.

PMID- 15971311
TI  - General principles for prescribing, recording and reporting a therapeutic
      irradiation.
AB  - Exchange of clinical information is essential for the development and progress in
      radiation oncology. This goal can be achieved only through a general
      harmonization on methods of reporting. The ICRU has been involved for several
      decades in a continuous effort to harmonize reporting of dose and to standardize
      methods used to determine the doses and points or volumes where these doses are
      delivered. Requirements for reporting proton and ion beam therapy should, in
      principle, be as similar as possible to reporting the current radiation therapy
      modalities. However, proton and ion therapy have their own clinical and technical
      uniqueness: in particular, they require definition of new clinical,
      radiobiological and technical concepts, and strict quality assurance programmes
      for efficient and safe clinical application. The current ICRU definitions of
      volumes are reviewed: Gross Tumour Volume (GTV), Clinical Target Volume (CTV),
      Planning Target Volume (PTV), Organs At Risk (OAR), Planning organ at Risk Volume
      (PRV), treated volume and reference volume. The irradiation conditions and the
      absorbed dose should always be reported together with the point(s) and/or
      volume(s) where the dose is delivered. In addition, the weighting factor W(RBE)
      introduced to take into account the RBE, and the related weighted dose D(RBE)
      have to be reported.

PMID- 15971312
TI  - The patient positioning concept for the planned MedAustron centre.
AB  - Especially for ion therapy, efficiency in form of patient throughput is becoming
      increasingly important, and here, patient positioning in treatment room isocenter
      is a key aspect. In order to ascertain high quality nonetheless, we suggest an
      alternative to the rigidly installed couch paradigm in form of real-time patient
      positioning onhand a ceiling mounted infrared photogrammetric system giving
      positioning information to a novel treatment couch with 6 degrees of freedom
      integrated on a rolling platform. All MedAustron treatment planning rooms and
      even the planning CT are not forseen to have a rigidly installed treatment couch.

PMID- 15971313
TI  - Moving targets: detection and tracking of internal organ motion for treatment
      planning and patient set-up.
AB  - BACKGROUND AND PURPOSE: Clinical target volumes of the thorax and abdomen are
      typically expanded to account for inter- and intrafractional organ motion.
      Usually, such expansions are based on clinical experience and planar observations
      of target motion during simulation. More precise, 4-dimensional motion margins
      for a specific patient may improve dose coverage of mobile targets and yet limit
      unnecessarily large field expansions. We are studying approaches to targeting
      moving tumors throughout the entire treatment process, from treatment planning to
      beam delivery. MATERIAL AND METHODS: Radio-opaque markers were implanted under CT
      guidance in the liver at the gross tumor periphery. Organ motion during light
      respiration was volumetrically imaged by 4D Computed Tomography. Marker motion
      was also acquired by fluoroscopy and compared with 4DCT data. During treatment,
      daily diagnostic x-ray images were captured at end-exhale and -inhale for patient
      setup and target localization. RESULTS: Based on the time-resolved CT data,
      target volumes can be designed to account for respiratory motion during
      treatment. Motion of the tumor as derived from 4DCT was consistent with
      fluoroscopic motion analysis. Radiographs acquired in the treatment room enabled
      millimeter-level patient set-up and assessment of target position relative to
      bony anatomy. Daily positional variations between bony anatomy and implanted
      markers were observed. CONCLUSIONS: Image guided therapy, based on 4DCT imaging,
      fluoroscopic imaging studies, and daily gated diagonstic energy set-up
      radiographs is being developed to improve beam delivery precision. Monitoring
      internal target motion throughout the entire treatment process will ensure
      adequate dose coverage of the target while sparing the maximum healthy tissue.

PMID- 15971314
TI  - Tracking of target motion using physically based modelling of organs.
AB  - In this paper, we describe a general methodology for the realistic reconstruction
      and animation of anatomic organs. In fact, in the scope of conformal radiotherapy
      and hadron therapy applications, we want to simulate the motion and the shape
      alteration of the internal anatomical objects and to input this knowledge to
      treatment planning. For the reconstruction, particle systems are used: firstly,
      surface shape of the considered organ is computed from a set of CT scan sections.
      Next, the volume defined by this surface is filled with particles. The coherency
      of the object is maintained due to the use of the classical Lennard-Jones inter
      particles force. This work permits to study the impact of the organs movement on
      the treatment of prostate and lung cancer. Our particle system has been suitably
      integrated in a radiation dose evaluation software, developed within an European
      BIOMED2 project and is currently supported by the French ETOILE project.

PMID- 15971315
TI  - 3D online compensation of target motion with scanned particle beam.
AB  - Intensity modulated, active beam delivery, like magnetic raster scanning,
      strongly relies on target immobilisation. If target motion cannot be avoided,
      interferences between the scanning procedure and the tumour displacement destroy
      the volume conformity. A prototype setup for 3D online motion compensation (3D
      OMC) with a scanned particle beam is described, transferring the full potential
      of volume conformal irradiation to moving targets.

PMID- 15971316
TI  - Treatment planning for scanned ion beams.
AB  - Since 1997 a radiotherapy unit using fast carbon ions is operational at GSI. An
      intensity-controlled magnetic raster scanner together with a synchrotron allowing
      fast energy variation enable a unique method of purely active dose shaping in
      three dimensions. This contribution describes the necessary steps to establish a
      treatment planning system for this novel modality. We discuss the requirements
      for the physical beam model and the radiobiological model. Based on these we
      chose to implement a home-grown pencil beam model to describe the ion-tissue
      interaction and the Local Effect Model to calculate the RBE voxel-by-voxel. Given
      the large number of degrees of freedom biological dose optimization must be
      achieved by means of inverse treatment planning. All ion-related aspects are
      collected in our TRiP98 software. Biological dosimetry measuring cell survival in
      two dimensions turns out to be a good way to verify the model predictions as well
      as the actual irradiation procedure. We show a patient example and outline the
      future steps towards a dedicated clinic facility for all light ions.

PMID- 15971317
TI  - Treatment planning for carbon ion radiotherapy in Germany: review of clinical
      trials and treatment planning studies.
AB  - The GSI carbon ion radiotherapy facility established the first completely active
      beam shaping system for heavy ions, using energy variation on the synchrotron and
      pencil beam scanning. The introduction of an active beam shaping system for
      carbon ions has considerable impact on the design of the treatment planning
      system (TPS). The TPS has to account for the capability of the beam delivery and
      the biological modelling, which is needed to calculate the RBE for the resulting
      varying depth dose modulation. The TPS used in clinical routine with carbon ions
      is described and its use in treatment planning studies are outlined. A clinical
      trial with carbon ion therapy as primary therapy for chordoma and chondrosarcoma
      of the base of skull has been completed in 2001. Currently, carbon ion therapy as
      a boost treatment together with conventional conformal photon therapy or IMRT is
      under investigation in clinical trials for adenoid cystic carcinoma, chordoma and
      chondrosarcoma of the cervical spine and sacrococcygeal chordoma. Treatment
      planning studies comparing carbon ion therapy with IMRT, using optimization of
      combination therapy, and optimization of beam-line design have already been
      completed. Analysis of uncertainties in treatment planning has been started with
      the investigation of range uncertainties stemming from CT imaging. Uncertainties
      coming from the beam delivery play only a minor role. An attempt to asses the
      uncertainties introduced in treatment plans by the biological modelling, was
      done, using phantom verification of calculated cell survival levels. The clinical
      trials and planning studies are of special importance for the upcoming new
      clinical ion facility of the Heidelberg university hospital.

PMID- 15971318
TI  - The fast neutron component in treatment irradiations with 12C beam.
AB  - Using 12C beams of 200 AMeV kinetic energy the production of secondary fragments
      from nuclear reactions in a thick water absorber (12.78 cm) was investigated.
      Fast neutrons and energetic charged particles (p-, d-, t-, a-particles) emitted
      in the forward hemisphere were identified by a BaF2/plastic-scintillation
      detector telescope. Neutron energy spectra were recorded at various angles using
      time-of-flight techniques. The neutron emission is forward peaked and the energy
      spectrum shows a broad maximum about half the energy per nucleon of the primary
      12C ions. The total yield of fast neutrons emitted into the forward hemisphere
      integrated over the energy range of 25 to 500 MeV was found to be 0.43 +/- 0.1
      per primary ion. The dose contribution of fast neutrons in patient treatments
      with carbon ions is estimated to be less than 1% of the total treatment dose.

PMID- 15971319
TI  - Dose quantification from in-beam positron emission tomography.
AB  - Positron emission tomography (PET) imaging of the radioactivity distributions
      induced by therapeutic irradiation is at present the only feasible method for an
      in situ and non-invasive monitoring of radiooncology treatments with ion beams.
      The clinical implementation of this imaging technology at the experimental carbon
      ion therapy facility at the Gesellschaft fur Schwerionenforschung (GSI) at
      Darmstadt, Germany is outlined and an interactive approach for a PET guided
      quantification of local dose deviations with respect to the treatment plan is
      presented.

PMID- 15971320
TI  - Investigations of dose response of BANG polymer-gels to carbon ion irradiation.
AB  - In this presentation BANG polymer-gel dosimetry using magnetic resonance imaging
      (MRI) is applied to densely ionizing radiation such as carbon ion beams. BANG
      polymer-gels were irradiated with monoenergetic 12C ions at an energy of 205
      MeVu(-1). The irradiation of the gels with doses up to 100 Gy were performed at
      the radiotherapy facility of the GSI, Darmstadt, Germany. For comparison with
      sparsely ionizing radiation data were obtained for 6 MV photon radiation, too. It
      was the object to examine the saturation effect for densely ionizing radiation
      that occurs at high values of linear energy transfer (LET). Up to now the dose
      response is unknown for mixed radiation fields of primary carbon ions. Therefore,
      to facilitate such conversions of measured MR signals into dose model
      calculations are proposed. This model relies only on heavy ion track structure
      and the experimentally determined photon response.

PMID- 15971321
TI  - The effect of proton-irradiation on the Raman spectroscopy of tissue samples.
AB  - Tumor and healthy tissue samples were irradiated by 24 MeV protons. The samples
      were exposed to doses from 0 to 50 Gy and subsequently examined by Raman
      spectroscopy. The analysis of the intensity of characteristic peaks as a function
      of radiation dose exhibits different trends for the two types of tissue.

PMID- 15971322
TI  - Track formation and electron emission in swift ion collisions with condensed
      matter.
AB  - Electron ejection from target atoms is one of the basic processes when ionizing
      radiation interacts with matter. The primary electrons and their subsequent
      secondary interactions lead to the deposition of energy around the ion
      trajectory. The detailed knowledge of the structure of these ion tracks is a key
      issue for our understanding of radiation effects in condensed matter, an
      important example being calculations of the RBE of heavy particles, where doubly
      differential electron ejection cross sections are a key input parameter. Usually,
      data obtained from single collisions, i.e. with gas targets, are used, but
      condensed matter effects may considerably alter the emission patterns. Therefore,
      we will focus on the primary ionization (binary encounter and soft electron
      emission), which is common to single atoms (gas targets) and condensed matter.
      Then, special emphasis will be given to discuss effects, which are only seen in
      condensed matter (electron transport and multiple scattering effects, jet-like
      structures, wake effects due to collective excitation of plasmons), but not in
      gaseous targets (single collisions).

PMID- 15971323
TI  - Direct visualisation of heavy ion induced DNA fragmentation using atomic force
      microscopy.
AB  - Atomic Force Microscopy of phiX174 plasmids irradiated in vitro was used to
      visualise the DNA fragmentation induced by heavy ions and to compare it to the
      fragmentation pattern obtained after X-irradiation. Fragment distributions
      induced by low ion fuences were found to be much more shifted towards small
      fragment sizes than the distributions obtained after corresponding doses of X
      rays. The average fragment length was found to be significantly smaller than the
      full plasmid length even for single ion traversals.

PMID- 15971324
TI  - Effects of low energy protons on clonogenic survival, DSB repair and cell cycle
      in human glioblastoma cells and B14 fibroblasts.
AB  - BACKGROUND AND PURPOSE: The reaction of human tumor cells and mammalian normal
      tissue to irradiation with low energy protons and X-rays was examined. MATERIAL
      AND METHODS: An irradiation facility with a vertical proton beam was set up at
      the Tandem accelerator at the University of Erlangen. U-138MG human glioblastoma
      cells and B14 hamster fibroblasts were irradiated with 5.7 and 7.0 MeV protons
      (LET 7.27 and 6.23 keV/microm) and with 120 kV X-rays. The inactivation was
      measured by the colony forming assay, induction and repair of DNA double strand
      breaks (DSB) by constant field gel electrophoresis and cell cycle control by
      image cytometry. RESULTS: An obvious reduction of the shoulder of the dose effect
      curve was determined. This effect was more pronounced for the glioblastoma cell
      line. The RBE at 10% survival was measured as 1.78 +/- 0.09 for glioblastoma
      cells and 1.18 +/- 0.06 for B14 fibroblasts. The induction of DNA DSB in
      glioblastoma cells showed an RBE of 0.96 +/- 0.06, after 24h repair time an RBE
      of 2.63 +/- 0.07 was calculated. Protons had a larger and enduring effect on G2
      arrest of cell cycle than X-rays, 72 hours after irradiation with 10 Gy an RBE of
      1.57 +/- 0.05 was calculated. CONCLUSIONS: The effect of higher LET irradiation
      was more distinct for tumor cells than for normal tissue. Both cell lines showed
      a higher RBE for cell survival than the value of 1.1 normally used for proton
      therapy. Repair capacity of DNA DSB was reduced following low energy proton
      irradiation and G2 arrest was induced to a larger degree. Further experiments are
      needed to elucidate if this could be a reason for lower cell survival.

PMID- 15971325
TI  - Radiation induced cell cycle arrest: an overview of specific effects following
      high-LET exposure.
AB  - PURPOSE: Up to now only few studies on high LET radiation-induced cell cycle
      arrest are available. Open questions still remain concerning magnitude,
      persistence and control of the cell cycle inhibition after high-LET exposure. The
      intention of this review is to focus on the cell cycle distribution of the
      irradiated populations and the cell systems used (normal vs. mutant and tumor
      cells). The relevant published data are summarized. CONCLUSIONS: Comparing
      isodoses, high-LET irradiation is a more potent inducer of cell cycle delays than
      low-LET irradiation. Generally, more pronounced delays in S- and G2-phase have
      been observed with increasing LET. The role of TP53 in relation to these effects
      is still controversial. A dose- and LET- dependent increase in cells arrested in
      G1-phase has as well been observed. Studies are presented indicating that a large
      fraction of normal fibroblasts irradiated in G1-phase and reseeded after
      exposure, did not re-enter the cell cycle but remained permanently arrested. The
      expression of cell cycle regulatory proteins in this case appeared more
      pronounced at high LET, but no fundamental differences were observed between low-
      and high-LET irradiation.

PMID- 15971326
TI  - Chromosome fragmentation after irradiation with C ions.
AB  - The premature chromosome condensation (PCC) technique has been used to compare
      chromatin breakage and repair in non-cycling CHO-K1 cells following high LET (C
      ions) and low LET (X-rays) irradiation. For both radiation qualities the average
      initial number of excess PCC fragments increases linearly with dose. However, the
      frequency of chromatin breaks follows the pattern of energy deposition and at
      higher LET values reveals clustering due to the large number of ionizing events
      being concentrated in a small volume of the cell nucleus. In consequence, the
      distribution of PCC chromosomes plus excess fragments among cells has followed
      Poisson statistics after X-ray irradiation while the overdispersion of the
      frequencies has been observed after C-irradiation indicating that a single
      particle traversal through a cell nucleus can produce multiple chromatin lesions.

PMID- 15971327
TI  - Radioprotective activities of beer administration for radiation-induced acute
      toxicity in mice.
AB  - BACKGROUND AND PURPOSE: We previously found that drinking beer reduces chromosome
      aberrations in blood lymphocytes that were collected and irradiated in vitro. In
      this study, we investigated the radioprotective activities of beer-administration
      for bone marrow and intestine in mice. METHODS: C3H/He female mice received an
      oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min
      before whole body irradiation with 137Cs gamma rays or LET 50 keV/microm carbon
      ions. Radioprotective activities were estimated using a LD(50/30) (The dose
      required to kill 50% of the mice within 30 days) and a microcolony technique for
      intestine. RESULTS: The LD(50/30) for the beer-administered mice was
      significantly increased in comparison with saline administered mice. The
      LD(50/30) of gamma-ray was 7.8 Gy (p < 0.05), 7.6 Gy and 7.3 Gy for beer-,
      ethanol- and saline-administered group, respectively. The LD(50/30) of carbon
      ions was 6.6 Gy (p < 0.05), 6.2 Gy and 5.9 Gy for the beer-, ethanol- and saline
      administered groups, respectively. The crypt survivals that were semi
      logarithmically plotted against dose were well fitted to a linear regression
      line. The dose reduction factor (DRF) (D10) of beer- and ethanol-administered
      mice for gamma rays was 1.09 and 1.08, respectively. The DRF (D10) of beer- and
      ethanol-administered mice for carbon ions was 1.08 and 1.07, respectively.
      CONCLUSIONS: The radioprotection by beer-administration is due to not only OH
      radical-scavenge action by the ethanol contained in beer.

PMID- 15971328
TI  - Biological effects of accelerated protons.
AB  - Radiobiological studies with proton beams started in the first half of the last
      century, when the scientific community could profit of the Lawrence idea to
      accelerate protons. It became soon clear that such a radiation could be
      favourably used in clinical applications. Since then, the biological effects of
      protons have been deeply investigated, in a wide energy range and several
      biological end-points have been studied. Nowadays a partially overlapping
      research field is expanding aiming at radioprotection of astronauts, a major
      concern because long-term manned space missions are foreseen.

PMID- 15971329
TI  - Late effects from hadron therapy.
AB  - Successful cancer patient survival and local tumor control from hadron
      radiotherapy warrant a discussion of potential secondary late effects from the
      radiation. The study of late-appearing clinical effects from particle beams of
      protons, carbon, or heavier ions is a relatively new field with few data.
      However, new clinical information is available from pioneer hadron radiotherapy
      programs in the USA, Japan, Germany and Switzerland. This paper will review
      available data on late tissue effects from particle radiation exposures, and
      discuss its importance to the future of hadron therapy. Potential late radiation
      effects are associated with irradiated normal tissue volumes at risk that in many
      cases can be reduced with hadron therapy. However, normal tissues present within
      hadron treatment volumes can demonstrate enhanced responses compared to
      conventional modes of therapy. Late endpoints of concern include induction of
      secondary cancers, cataract, fibrosis, neurodegeneration, vascular damage, and
      immunological, endocrine and hereditary effects. Low-dose tissue effects at tumor
      margins need further study, and there is need for more acute molecular studies
      underlying late effects of hadron therapy.

PMID- 15971330
TI  - Radiation tolerance of healthy tissues, high-LET beam particularities.
AB  - The sensitivity of healthy tissue is the limit of radiation therapy. Most of the
      technological progress of radiotherapy along its history have been devoted to
      improve the sparing of healthy tissues while increasing the tumor dose. The use
      of hadrons has been justified first for neutrons by radiobiological
      considerations (high RBE and no oxygen effect), then for protons by ballistic
      considerations (Bragg peak). Neutron ballistic is so unfavourable and side
      effects are so important when large and deep tumors are irradiated that their
      indications have been dramatically reduced and no recent studies on late effect
      after high RBE irradiation have been carried out. Therefore, the renewal use,
      hopefully on a large scale, of high RBE beam such as carbon ions, demands a new
      appraisal of the radiation tolerance of healthy tissues. From the photon and the
      neutron experience should be drawn: (i) the typology of late effect; (ii) the
      time schedule of the observation, (iii) the equivalent dose associated with
      observable late effects; (iv) dose limitations according to the type of tissues,
      the acceptable adverse effects, the security required and the RBE of the part of
      the beam irradiating the healthy tissues. Commune scale and description of the
      late effects will have to be decided. The biological mechanisms of late effects
      associating slow cellular lost, micro vascular failure and active fibrosis will
      need further investigation in the frame of high RBE irradiation.

PMID- 15971331
TI  - Fibrosis and cytokine mechanisms: relevant in hadron therapy?
AB  - BACKGROUND: Cytokines are important for signalling between cells and tissues and
      constitute a humoral component of the response of cells and tissues to
      radiotherapy. Although several cytokines have been implicated in mediating
      radiation-induced reactions of normal tissues to both conventional photon and
      heavy ion irradiation, the mechanisms are only beginning to be elucidated.
      MATERIAL AND METHODS: Published and own data on radiation-induced cytokine
      expression from cell culture and clinical studies are reviewed. Current models of
      cytokine-mediated multicellular interactions in radiation-induced reactions are
      presented. RESULTS AND CONCLUSION: The major cytokines in the radiation response
      of non-hemopoietic tissues include IL-6, IL-1, TNF-alpha and TGF-beta. Different
      cell types interact via cytokines in a complex network of effector and receptor
      cells, including inflammatory cells, tissue-specific functional cells and
      fibroblasts. TGF-beta appears to be of particular importance in the development
      of late reactions to radiation therapy, such as fibrosis, in response to both
      conventional therapy as well as hadron therapy.

PMID- 15971332
TI  - Intestinal crypt regeneration in mice: a biological system for quality assurance
      in non-conventional radiation therapy.
AB  - BACKGROUND AND PURPOSE: The Relative Biological Effectiveness (RBE) of 8 fast
      neutron beams, 5 proton beams and 1 carbonion beam was determined using as
      biological criterion intestinal crypt regeneration in mice, i.e. an in vivo
      system. These beams are used or planned for clinical cancer therapy applications.
      In addition, the RBE of 6 epithermal neutron beams, used or planned for Boron
      Neutron Capture Therapy (BNCT), was determined; no boron was administered. The
      goal of the program was to improve the exchange of information between the
      centers, facilitate the interpretation of the results and increase the safety of
      the clinical applications. MATERIALS AND METHODS: In all visited centers, the
      same technique was applied in the same conditions by the same radiobiology team.
      The number of regenerating crypts per circumference was scored 3.5 days after
      single fraction total body irradiation. The control irradiations were performed
      locally using cobalt-60 units. The mice were randomized according to radiation
      quality and dose level. RESULTS: (1) For fast neutron beams, the RBE (Ref. cobalt
      60 gamma rays) increases with decreasing energy (from approximately 1.7 for
      p(65)+Be neutrons to approximately 2.4 for d(14.5)+Be neutrons). In addition, it
      is specific to each facility and depends on the nuclear reaction (p or d + Be),
      target and collimation type. (2) For proton beams, the RBEs (Ref cobalt-60 gamma
      rays) at the reference position (middle of a 7-cm Spread Out Bragg Peak, SOBP)
      range between 1.08 and 1.18. They might differ by approximately 6-8% according to
      the mode of beam production or delivery. The RBEs at the end of the SOBP are
      always 5-10 % higher than at the middle of the SOBP. (3) For the carbon ion beam
      studied at NIRS in Chiba, Japan, the RBE significantly increases with depth.
      Relative to gamma rays, it ranges from 1.3 in the initial plateau, 1.6 at the
      beginning, 1.7 at the middle and 1.9 at the end of a 6-cm SOBP. 4) In BNCT beams,
      the radiation quality (in particular the relative contribution of the different
      dose components) varies rapidly with depth and depends strongly on the
      arrangement of the irradiation set-up (e.g. presence or not of back scattering
      material). Moreover, the (total) dose rates are highly variable (from 0.05 to
      approximately 0.5 Gy/min) according to the power of the reactors. Wide range of
      RBE values (Ref. gamma rays) was thus obtained (RBE = 1.4 - 2.2) at shallow
      depths of 1.5 - 2.5 cm. DISCUSSION AND CONCLUSION: Intestinal crypt regeneration
      in mice is an in vivo system perfectly suitable to perform intercomparisons
      between centers applying different types of non-conventional radiation qualities.
      It was proven to be reproducible, reliable and accurate, and becomes
      progressively recognized worldwide as part of the Quality Control (QA) procedures
      for new beams. It should be stressed that the observed RBE for intestinal crypt
      cells after a single high dose provide some radiobiological characterization of
      the radiation quality but cannot be used as the RBE weighting factor in clinical
      prescriptions.

PMID- 15971333
TI  - Cell transformation by light charged particles: review of available data.
AB  - Data reported in the literature on neoplastic transformation induced in cultured
      cells by light charged particles are compared and analyzed as a function of LET
      and dose protraction. Light charged particles RBE for transformation is maximum
      between 75 and 120 keV/microm. The majority of the data suggest that RBE values
      for survival and transformation are of similar magnitude. Dose protraction
      effects on transformation induction depend on dose, dose rate and on radiation
      quality.

PMID- 15971334
TI  - Heavy ion radiobiology for hadrontherapy and space radiation protection.
AB  - Research in the field of biological effects of heavy charged particles is needed
      for both heavy-ion therapy (hadrontherapy) and protection from the exposure to
      galactic cosmic radiation in long-term manned space missions. Although the
      exposure conditions (e.g. high- vs. low-dose rate) and relevant endpoints (e.g.
      cell killing vs. neoplastic transformation) are different in the two fields, it
      is clear that a substantial overlap exists in several research topics. Three such
      topics are discussed in this short review: individual radiosensitivity, mixed
      radiation fields, and late stochastic effects of heavy ions. In addition,
      researchers involved either in experimental studies on space radiation protection
      or heavy-ion therapy will basically use the same accelerator facilities. It seems
      to be important that novel accelerator facilities planned (or under construction)
      for heavy-ion therapy reserve a substantial amount of beamtime to basic studies
      of heavy-ion radiobiology and its applications in space radiation research.

PMID- 15971335
TI  - RBE of carbon ions: experimental data and the strategy of RBE calculation for
      treatment planning.
AB  - The main reason for the application of heavy ions like carbon in radiotherapy is
      the enhanced relative biological effectiveness RBE. In contrast to neutrons where
      RBE is widely independent from penetration depth, high energy carbon beams have a
      low RBE at the entrance and a high RBE in the target-volume. Therefore, the side
      effects to normal tissue are small, while the tumor response can be maximized. In
      the paper, experimental RBE values for inactivation are compiled, that
      demonstrate the RBE dependence from the repair capacity. In a theoretical
      approach, the local effect model (LEM), this dependence is used to calculate
      clinical RBE. Examples for clinical RBEs are given that have been applied to
      patient treatments.

PMID- 15971337
TI  - Cellular parameters and RBE-LET dependences for modelling heavy-ion radiotherapy.
AB  - Sets of four parameters (m, E0, sigma0 and kappa) of the cellular track structure
      model of Katz have been fitted to recently published data concerning human
      melanoma (AA) and mammalian (V79) cells exposed to a variety of lighter ions and
      to mixed ion-Co60 and ion-ion irradiation. Using these parameters, model
      predictions of V79 survival were verified against experimental data. RBE-LET
      dependences were calculated and compared with experimental data obtained for V79
      cells after exposure to 3He, 12C and 20Ne ion beams. The presented track-segment
      approach used in track structure calculations, while satisfactory for heavier
      ions, may be of limited value for predicting the RBE-LET dependence of proton and
      helium radiotherapy beams in regions close to the distal range of these
      particles. We discuss the predictive capability of this model and propose
      standards in reporting cellular radiobiology data for application in modelling
      heavy ion beam radiotherapy.

PMID- 15971336
TI  - Role of DNA organisation and environmental scavenging capacity in the evolution
      of radiobiological damage: models and simulations.
AB  - BACKGROUND AND PURPOSE: Theoretical models and Monte Carlo simulations were
      developed, aimed to investigate the role played by the organisation of interphase
      DNA and the environmental scavenging capacity conditions in the induction of
      radiobiological damage. METHODS: The induction of single- and double-strand
      breaks by gamma rays impinging on different DNA structures (e.g. linear DNA, SV40
      minichromosome and cellular DNA) was simulated as a function of the environment
      scavenging capacity. Furthermore, yields of chromosome aberrations (CA) induced
      by gamma rays and light ions were simulated with a purposely developed MC code
      that explicitly takes into account the DNA higher-order organisation as
      chromosome territories. RESULTS AND CONCLUSIONS: Simulations performed with the
      PARTRAC code allowed quantification of the dependence of dsb and ssb both on the
      target structure, and on the scavenging capacity. The results relative to CA
      showed the importance of DNA damage complexity (nanometre scale) and interphase
      chromosome domains (micrometre scale) in the process of aberration formation.
      Very good agreement was found between the model predictions on ssb, dsb and CA
      and available experimental data.

PMID- 15971338
TI  - RBE and weighting of absorbed dose in ion-beam therapy.
AB  - Absorbed dose is the fundamental quantity used to quantify the exposure of any
      biological system to ionizing radiation. However, the relationship between dose
      and biological effect is not unique but varies with fractionation and time
      factor(s), radiation quality and irradiation conditions. In radiation therapy,
      weighting factors are used to correlate absorbed dose and clinical effects when
      altering irradiation conditions, or for combining or comparing different
      technical modalities. For some well established therapy modalities (e.g.
      fractionated photon beam therapy), a general agreement on weighting factors has
      been reached: it is based on the linear-quadratic model. For neutron, proton or
      ion therapy, the differences in radiation quality are currently accounted for
      using a diversity of methods (almost hospital specific). This paper reviews the
      current approaches used for evaluating or selecting the weighting factors and
      their application in clinical practice. The weighting factors take account of the
      RBE and other factors, such as fractionation when needed. Harmonization of these
      approaches will facilitate the exchange of information within the radiation
      oncology community and between centres using different technical modalities. In
      any case, when reporting the treatments, absorbed dose and irradiation conditions
      should always be specified in addition to the weighting factor and the weighted
      dose.

PMID- 15971339
TI  - Light ion facility projects in Europe: methodological aspects for the calculation
      of the treatment cost per protocol.
AB  - In the framework of the European Network for Research in Light Ion Hadron Therapy
      (ENLIGHT), the health economics group develops a methodology for assessing
      important investment and operating costs of this innovative treatment against its
      expected benefits. The main task is to estimate the cost per treated patient. The
      cost analysis is restricted to the therapeutic phase from the hospital point of
      view. An original methodology for cost assessment per treatment protocol is
      developed based on standard costs. Costs related to direct medical activity are
      based on the production process analysis, whereas indirect and non direct medical
      costs are allocated to each protocol using relevant cost-drivers. The resulting
      cost model will take into account the specificities of each therapeutic protocol
      as well as the particularities of each of the European projects.

PMID- 15971340
TI  - The Heidelberg Ion Therapy Center.
AB  - The ion beam therapy facility presently under construction at the Department of
      Clinical Radiology, University of Heidelberg, Germany, will be the first
      dedicated and hospital-based irradiation facility for protons and heavier ions in
      Europe. A capacity of more than 1000 patient treatments per year is planned. The
      facility comprises two horizontally-fixed beamlines for patient treatments plus a
      fixed-beam experimental area. In addition, the world-wide first scanning ion
      gantry is under construction. The facility fully relies on an active beam
      delivery method, the intensity-controlled rasterscan technique. The availability
      of different ion species ranging from protons to oxygen under identical
      conditions optimally supports clinical trials aiming to clarify the question of
      which particle species is best suited for the individual indications. A linac
      synchrotron combination will deliver libraries of energy-, focus- and intensity
      variable pencil-beams for each ion species to the dose-delivering scanning
      systems at each treatment station. The available energies correspond to water
      equivalent ranges from 2 cm to 30 cm. The intensity-controlled rasterscan
      technique allows for the administration of inversely planned and biologically
      optimized dose distributions having utmost precision. The facility will be
      equipped with state-of-the-art imaging modalities as well as an in-situ Positron
      Emission-Tomography (PET). The commissioning of the different sections is
      scheduled for 2006. The pre-clinical operation will start early in 2007 followed
      by the routine patient treatment.

PMID- 15971341
TI  - CNAO--The Italian Centre for Light-Ion Therapy.
AB  - In 1991 the author involved the Italian institute of nuclear physics (INFN) in
      R&D work in the field of hadrontherapy. In 1992 the TERA Foundation was created
      with the purpose of forming and employing people fully devoted to the design,
      promotion and construction of hadrontherapy centres in Italy and in Europe. The
      present contribution describes the main project of TERA, the CNAO (Centro
      Nazionale di Adroterapia Oncologica), and the status of its construction in
      Pavia. The Italian Centre is based on the optimised medical synchrotron designed
      in the framework of the "Proton Ion Medical Machine Study" (PIMMS) carried out at
      CERN from 1996 to 2000 with CERN, the Med-AUSTRO project, Oncology 2000 (Prague)
      and TERA as partners. In the following years TERA introduced modifications and
      improvements in the original PIMMS design producing what is now dubbed the
      PIMMS/TERA design. Since 2001 the construction of CNAO has been endorsed by the
      Italian government to the CNAO Foundation formed by five major hospitals, seated
      in Milan and Pave, and by TERA. Since 2003 INFN is an Institutional Participant.
      The site chosen at the beginning of 2003 (37,000 m2) is in the close vicinities
      of one of the five hospitals, the San Matteo University Hospital of Pave. The
      construction plan foresees the treatment of the first patient at the end of 2007.

PMID- 15971342
TI  - The status of MedAustron.
AB  - This paper describes the status of the design study of the Austrian Ion Therapy
      and Cancer-Research Centre Project MedAustron. This work was performed during the
      last two years by the MedAustron study group. The team was spread out over
      several research institutes and University clinics, with full-time members at the
      Medical University of Vienna, Innsbruck Medical University and Fotec, Wiener
      Neustadt in collaboration with the Medical University Graz, the Hospital of
      Wiener Neustadt, the Vienna University of Technology and the research institutes
      CERN, PSI, the Slovak University of Technology in Bratislava and the Jozef Stefan
      Institute, Ljubljana. The study group has also worked in cooperation with GSI,
      Darmstadt and the CNAO foundation, Milan. The agreed aim of this study was to
      investigate a conceptual design of an accelerator facility which provides optimum
      treatment conditions for high-precision active beam scanning of cancer tumours
      with both proton and carbon ions.

PMID- 15971343
TI  - Development of light ion therapy at the Karolinska Hospital and Institute.
AB  - Recent developments in radiation therapy have made it possible to optimize the
      high dose region to cover almost any target volume and shape at the same time as
      the dose level to adjacent organs at risk is acceptable. Further implementations
      of IMRT (Intensity Modulated Radiation Therapy), and inverse treatment planning
      using already available technologies but also foreseeable improved design of
      therapy accelerators delivering electron- and photon beams, will bring these
      advances to the benefit of a broad population of cancer patients. Protons will
      therefore generally not be needed since in most situations the improvement will
      be insignificant or moderate due to the large lateral penumbra with deep proton
      therapy. A further step would be to use He-ions, which have only half the
      penumbra width of protons and still a fairly low-LET in the spread-out Bragg
      peak. There is however still a group of patients that cannot be helped by these
      advances as the tumor might be radioresistant for the presently utilized low
      ionization density beam qualities. The ultimate step in the therapy development
      process should therefore be to optimize the beam quality for each tumor-normal
      tissue situation. To facilitate beam quality optimization light ions are needed.
      It is argued that in many radioresistant tumors a dose-mean LET of 25-50 eV/nm in
      the target would be optimum as then tumor cells will be lost in the highest
      proportion through apoptotic cell kill and the superficial tissues will still be
      irradiated with a fairly low LET. Light ions using Li, Be, B, and C would then be
      the ideal choice. In this paper a light ion facility is outlined for the
      Karolinska University Hospital facilitating both dose distribution and beam
      quality optimization.

PMID- 15971344
TI  - Status of the "ETOILE" project for a French hadrontherapy centre.
AB  - It is proposed to build a national centre for light-ion hadrontherapy in France,
      located in Lyon in the Rhone-Alpes region. Under the auspices of University
      Claude Bemard Lyon-I and with the support of a research contract between Rhone
      Alpes region and the Minister of Research, a design has been elaborated. This
      paper reviews the medical and technical characteristics of the project, called
      ETOILE (Espace de Traitement Oncologique par Ions Legers dans le cadre Europeen).
      The research programs associated with ETOILE concern mainly the tracking of
      moving organs, the design of an in-beam PET detector, the simulation of the
      interaction of carbon ions with tissues and radiobiological studies on the
      radiosensitivity and tolerance of normal tissues and on the radioresistance of
      tumours. The capital cost needed to realize ETOILE is about 90 M Euro. We expect
      a definitive decision to build ETOILE at the end of 2004. In that case the centre
      will treat its first patients in 2009. A routine flux of 1000 patients per year
      will be reached after 3 years with an operation cost of 15 M Euro.

PMID- 15971345
TI  - Assertive case management for triply diagnosed clients.

PMID- 15971347
TI  - The impatient visitor to the African epidemic.

PMID- 15971346
TI  - Triple diagnosis: an overview.

PMID- 15971349
TI  - The right to questions: psychiatric care in Zimbabwe.

PMID- 15971348
TI  - HIV in Uganda: does ABC work?

PMID- 15971350
TI  - A decade ends, another begins.

PMID- 15971351
TI  - On the occasion of our 10th anniversary.

PMID- 15971352
TI  - PIs associated with increased risk of cardiovascular disease.

PMID- 15971353
TI  - Treating morphologic and metabolic complications in HIV-infected patients on
      antiretroviral therapy. A consensus statement of an advisory committee of the
      International Association of Physicians in AIDS Care.
AB  - OBJECTIVE: Clinicians are increasingly challenged by presentation of morphologic
      and metabolic complications in HIV-infected patients. These complications are
      associated with HIV infection and/or combination antiretroviral therapy. This
      Consensus Statement is intended to offer guidance to clinicians actively involved
      in HIV/AIDS care. PARTICIPANTS: Seven clinicians with expertise in HIV medicine
      were invited by the International Association of Physicians in AIDS Care (IAPAC)
      to serve on an ad hoc Advisory Committee. CONSENSUS PROCESS: IAPAC convened the
      Advisory Committee to develop a draft Consensus Statement. Each clinician was
      tasked with drafting a specific section of the Consensus Statement corresponding
      with his or her expertise around a morphologic and/or metabolic complication.
      Scientific and clinical research, and other data in published literature and
      abstracts from scientific conferences were considered by strength of evidence.
      This document represents the consensus agreement of the Advisory Committee.

PMID- 15971354
TI  - Does GB virus C protect against HIV disease progression?

PMID- 15971356
TI  - Mitochondrial myopathy, sideroblastic anemia, and lactic acidosis: an autosomal
      recessive syndrome in Persian Jews caused by a mutation in the PUS1 gene.
AB  - We report the seventh case of autosomal recessive inherited mitochondrial
      myopathy, lactic acidosis, and sideroblastic anemia The patient, a product of
      consanguineous Persian Jews, had the association of mental retardation,
      dysmorphic features, lactic acidosis, myopathy, and sideroblastic anemia. Muscle
      biopsy demonstrated low activity of complexes 1 and 4 of the respiratory chain.
      Electron microscopy revealed paracrystalline inclusions in most mitochondria.
      Southern blot of the mitochondrial DNA did not show any large-scale
      rearrangements. The patient was found to be homozygous for the 656C-->T mutation
      in the pseudouridine synthase 1 gene (PUS1). Mitochondrial myopathy, lactic
      acidosis, and sideroblastic anemia is an oxidative phosphorylation disorder
      causing sideroblastic anemia, myopathy, and, in some cases, mental retardation
      that is due to mutations in the nuclear-encoded PUS1 gene. This finding provides
      additional evidence that mitochondrial ribonucleic acid modification impacts the
      phenotypic expression of oxidative phosphorylation disorders.

PMID- 15971355
TI  - Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated
      with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET).
AB  - Tuberous sclerosis complex is commonly associated with medically intractable
      seizures. We previously demonstrated that high uptake of alpha-[11C]methyl-L
      tryptophan (AMT) on positron emission tomography (PET) occurs in a subset of
      epileptogenic tubers consistent with the location of seizure focus. In the
      present study, we analyzed the surgical outcome of children with tuberous
      sclerosis complex in relation to AMT PET results. Seventeen children (mean age
      4.7 years) underwent epilepsy surgery, guided by long-term
      videoelectroencephalography (EEG) (including intracranial EEG in 14 cases),
      magnetic resonance imaging (MRI), and AMT PET. AMT uptake values of cortical
      tubers were measured using regions of interest delineated on coregistered MRI and
      were divided by the value for normal-appearing cortex to obtain an AMT uptake
      ratio. Based on surgical outcome data, tubers showing increased AMT uptake
      (uptake ratio greater than 1.00) were classified into three categories: (1)
      epileptogenic (tubers within an EEG-defined epileptic focus whose resection
      resulted in seizure-free outcome), (2) nonepileptogenic (tubers that were not
      resected but the patient became seizure free), or (3) uncertain (all other
      tubers). Increased AMT uptake was found in 30 tubers of 16 children, and 23 of
      these tubers (77%) were located in an EEG-defined epileptic focus. The tuber with
      the highest uptake was located in an ictal EEG onset region in each patient.
      Increased AMT uptake indicated an epileptic region not suspected by scalp EEG in
      four cases. Twelve children (71%) achieved seizure-free outcome (median follow-up
      15 months). Based on outcome criteria, 19 of 30 tubers (63%) with increased AMT
      uptake were epileptogenic, and these tubers had significantly higher AMT uptake
      than the nonepileptogenic ones (P = .009). Tubers with at least 10% increase of
      AMT uptake (in nine patients) were all epileptogenic. Using a cutoff threshold of
      1.02 for AMT uptake ratio provided an optimal accuracy of 83% for detecting
      tubers that needed to be resected to achieve a seizure-free outcome. The findings
      suggest that resection of tubers with increased AMT uptake is highly desirable to
      achieve seizure-free surgical outcome in children with tuberous sclerosis complex
      and intractable epilepsy. AMT PET can provide independent complementary
      information regarding the localization of epileptogenic regions in tuberous
      sclerosis complex and enhance the confidence of patient selection for successful
      epilepsy surgery.

PMID- 15971357
TI  - Palliation of pain.

PMID- 15971358
TI  - Alexithymia and grief reactions in bereaved Japanese women.
AB  - To examine the relationship between grief reactions and alexithymia, 54 Japanese
      women (33 outpatients attending a psychosomatic clinic and 21 normal healthy
      participants) completed the Texas Inventory of Grief (TIG), the 20-item Toronto
      Alexithymia Scale (TAS-20), and the Profile of Mood States (POMS). Each woman had
      experienced the death of a spouse or a first-degree relative. The TIG scores were
      positively correlated to the scores on the first TAS-20 factor of Difficulty
      Identifying Feelings and on the POMS tension-anxiety and depression scales. The
      scores on the first TAS-20 factor were higher in the psychosomatic group than in
      the normal group. Complicated grief reactions may be closely associated with both
      alexithymic character and mood states in bereaved Japanese women.

PMID- 15971359
TI  - Marine actinobacteria: perspectives, challenges, future directions.
AB  - In this paper we evaluate the current state of research on the biology
      biotechnology of marine actinobacteria. The topics covered include the abundance,
      diversity, novelty and biogeographic distribution of marine actinobacteria,
      ecosystem function, bioprospecting, and a new approach to the exploration of
      actinobacterial taxonomic space. An agenda for future marine actinobacterial
      research is suggested based upon consideration of the above issues.

PMID- 15971360
TI  - Getting unstuck: the roles of hope, finding meaning, and rumination in the
      adjustment to bereavement among college students.
AB  - The relationships between hope, bereavement-related rumination, and finding
      meaning (making sense and benefit finding) were examined in 158 college students
      who experienced the death of a loved one within the latter half of their lives.
      Greater rumination was related significantly to lessened psychological well
      being, and it mediated the relationship between being able to make sense of the
      death and superior well-being. Finding benefits in bereavement was associated
      with positive adjustment for those who recently experienced the death of a loved
      one, whereas it was related to negative adjustment for those who experienced the
      death longer ago. Higher hope predicted greater well-being, but it was not
      related to rumination or finding meaning.

PMID- 15971362
TI  - A public culture for guinea pigs: US human research subjects after the Tuskegee
      study.

PMID- 15971361
TI  - Mapping brains without coordinates.
AB  - Brain mapping has evolved considerably over the last century. While most emphasis
      has been placed on coordinate-based spatial atlases, coordinate-independent
      parcellation-based mapping is an important technique for accessing the multitude
      of structural and functional data that have been reported from invasive
      experiments, and provides for flexible and efficient representations of
      information. Here. we provide an introduction to motivations, concepts,
      techniques and implications of coordinate-independent mapping of
      microstructurally or functionally defined brain structures. In particular, we
      explain the problems of constructing mapping paths and finding adequate
      heuristics for their evaluation. We then introduce the three auxiliary concepts
      of acronym-based mapping (AM), of a generalized hierarchy (GM ontology), and of a
      topographically oriented regional map (RM) with adequate granularity for mapping
      between individual brains with different cortical folding and between humans and
      non-human primates. Examples from the CoCoMac database of primate brain
      connectivity demonstrate how these concepts enhance coordinate-independent
      mapping based on published relational statements. Finally, we discuss the
      strengths and weaknesses of spatial coordinate-based versus coordinate
      independent microstructural brain mapping and show perspectives for a wider
      application of parcellation-based approaches in the integration of multi-model
      structural, functional, and clinical data.

PMID- 15971363
TI  - Creating public alienation: expert cultures of risk and ethics on GMOs.

PMID- 15971364
TI  - Regulatory science as culture: contested two-dimensional values at the US FDA.

PMID- 15971365
TI  - Selling the life sciences: promises of a better future in biotechnology
      advertisements.

PMID- 15971366
TI  - Re-examining geneticization: family trees in breast cancer genetics.

PMID- 15971367
TI  - Eugenics perpetuated by altruism.

PMID- 15971368
TI  - Gift relationships in genetics research.

PMID- 15971369
TI  - Genomic capital: public cultures and market logics of corporate biotechnology.

PMID- 15971370
TI  - The first 'designer baby': the role of narratives, cliches and metaphors in the
      year 2000 media debate.

PMID- 15971371
TI  - Intersecting discourses: MMR vaccine and BSE.

PMID- 15971372
TI  - An emptying quiver: antimicrobial drugs and resistance.

PMID- 15971373
TI  - [Apoptosis: decision rests with the mitochondrion].

PMID- 15971374
TI  - [Are cells engineering their own genomes?].

PMID- 15971375
TI  - [Gene expression regulation of the heat shock protein hsp70i].

PMID- 15971376
TI  - [Acidic ribosomal proteins and their role in regulation of translation].

PMID- 15971377
TI  - [Polymorphism in detoxifying enzymes].

PMID- 15971378
TI  - [G protein-coupled receptors (GPCR), ligand-receptor interaction studies].

PMID- 15971379
TI  - [The role of cysteine cathepsins and their inhibitors in physiological and
      neoplastic processes].

PMID- 15971380
TI  - [Calcium dependent protein kinases].

PMID- 15971381
TI  - [Structure and regulation of nitrate reductase].

PMID- 15971382
TI  - The need for longitudinal screening studies in prison TB control.

PMID- 15971383
TI  - The role of gender and literacy in the diagnosis and treatment of tuberculosis.

PMID- 15971384
TI  - Tuberculosis infection among HCWs.

PMID- 15971385
TI  - Non-tuberculosis opportunistic infections and other lung diseases in HIV-infected
      infants and children.
AB  - The diagnosis and management of human immunodeficiency virus (HIV) infected
      infants and children who do not respond to recommended empiric therapy for acute
      or chronic pneumonia is a frequent clinical challenge, especially as the greatest
      burden of childhood HIV-related lung disease occurs in low-income regions where
      options for investigation and treatment are limited. Lung disease is due to a
      wider spectrum of causes in HIV-infected than non-infected children. Bacterial
      pneumonia, viral pneumonia and pulmonary tuberculosis (TB) are common in children
      throughout the developing world, and the added impact of HIV infection on the
      incidence and outcome of these diseases is covered in companion articles. This
      review focuses on lung diseases that are more specifically HIV-related.
      Pneumocystis jirovecii pneumonia (PJP) is a major cause of pneumonia and death in
      HIV-infected infants, especially in regions where maternal HIV status is often
      not known and the provision of PJP prophylaxis for HIV-exposed infants is
      unusual. Cytomegalovirus is commonly found in the lungs of HIV-infected infants,
      with implications for the use of corticosteroids for PJP. Lymphoid interstitial
      pneumonitis, a common cause of persistent respiratory symptoms in HIV-infected
      children, must be differentiated from pulmonary or miliary TB. The incidence of
      uncommon causes such as fungal pneumonia or HIV-related pulmonary malignancy
      varies among regions. The burden of lung disease due to opportunistic infections
      would be significantly reduced by more widely applying available measures that
      reduce mother-to-child HIV transmission, by providing cotrimoxazole prophylaxis
      for HIV-exposed infants, and by increasing the availability of antiretroviral
      therapy.

PMID- 15971386
TI  - The incidence of adult asthma: a review.
AB  - In recent years, several new studies have estimated the incidence of adult
      asthma. These studies vary in design and quality. The current paper summarises
      the findings of major population studies in the adult incidence of asthma. The
      pooled estimate of the adult incidence of asthma was 4.6 per 1000 person-years in
      women and 3.6 per 1000 person-years in men. The estimate among only general
      population cohort studies was higher, respectively 5.9 and 4.4 per 1000 person
      years in women and men. The adult incidence of asthma was slightly higher in
      women than men. In the few studies that allowed the incidence of asthma to be
      estimated among those aged >50 years, there was a trend towards a higher
      incidence with age. It is thought likely that this is at least partly explained
      by misclassification with COPD. However, the current findings from these studies
      may imply that the incidence of asthma in the elderly has previously been under
      estimated. Finally, the review shows that estimates of adult asthma incidence
      have tended to be higher in later studies, implying a rise in asthma incidence in
      adults within the timeframe of observation.

PMID- 15971387
TI  - Risk factors for prevalence of and mortality related to restriction on
      spirometry: findings from the First National Health and Nutrition Examination
      Survey and follow-up.
AB  - OBJECTIVE: To define risk factors for both restriction on spirometry and
      subsequent mortality in a national cohort of US adults. METHODS: Participants in
      the First National Health and Nutrition Examination Survey (NHANES I) were
      followed for up to 22 years. Subjects were classified using the forced expiratory
      volume in one second (FEV1), the forced vital capacity (FVC), and the FEV1/FVC
      ratio into subgroups with and without restriction on spirometry. Regression
      models were developed to determine risk factors for restriction on spirometry and
      death. RESULTS: Our final cohort consisted of 4320 subjects, of whom 481 (10.3
      weighted %) had restriction on spirometry. The largest risk factors for
      restriction on spirometry were a cardiothoracic ratio of >55% (OR 4.3, 95%CI 3.1
      5.9), race other than black or white (OR 3.7, 95%CI 1.8-7.8), and a history of
      stroke or paralysis (OR 1.8, 95%CI 1.1-2.9). The overall mortality rate was
      increased in subjects with restriction on spirometry (25.7 vs. 10.3 deaths per
      1000 person-years). CONCLUSIONS: Restriction on spirometry is associated with
      comorbid disease and increased mortality, and is present in a significant
      proportion of the population.

PMID- 15971388
TI  - Epidemiology of lung cancer in Sardinia, Italy, from 1980 to 1996.
AB  - SETTING: Bronchial carcinoma is the most common cause of death among all
      malignant tumours. Despite a progressive increase, many Italian regions--ours
      included--do not have a Regional Cancer Registry. OBJECTIVE: To assess lung
      cancer incidence and mortality rates in Sardinia during the period 1980-1996.
      METHODS: Data were gathered by consulting hospital registers and the case notes
      of individual patients released from hospital with a diagnosis of bronchial
      carcinoma at all Sardinian medical centres between 1980 and 1996. RESULTS: A
      total of 7734 patients with lung cancer were registered in Sardinia between 1980
      and 1996. Data showed a steady increase in lung cancer incidence rates over the
      years (from 22.3/100000 in 1980 to 34.5 in 1996). The same increase was evident
      in mortality rates (from 25.7/100000 in 1980 to 42.9 in 1996). The increase in
      mortality rates was higher in women (+146%) than in men (+59.5%). CONCLUSIONS:
      Results show a slow but steady increase in lung cancer incidence and mortality
      rates in Sardinia. The high number of smokers among lung cancer patients seems to
      indicate that anti-smoking campaigns need to be more effective in Sardinia.

PMID- 15971389
TI  - Chest radiograph screening for tuberculosis in a Hong Kong prison.
AB  - SETTING: Long-stay prisoners are not regularly screened for TB in Hong Kong.
      OBJECTIVE: To evaluate tuberculosis (TB) screening in prison. METHOD: All
      prisoners in a maximum security prison as of 31 October 2001 were screened by
      chest radiograph (CXR), except for those being followed up for TB or examined by
      CXR in the last 6 months. RESULTS: A total of 814 male prisoners aged 34.6 +/-
      9.6 (mean +/- SD) years were successfully screened. Of 53 cases (6.51%) with
      radiographic abnormalities, 10 active TB cases (8 culture-negative, 2 culture
      positive) were diagnosed, giving an overall yield of 1.23% (95%CI 0.59-2.26).
      There was no statistical difference in age, ethnicity, place of birth or
      residency status between those with and those without TB (all P > 0.05).
      Incarceration > or = 2 years, being in current prison > or = 2 years and not
      having CXR in last 2 years were associated with TB in univariate analysis (all P
      < 0.05), but only the last remained an independent predictor in multiple logistic
      regression (OR 16.8, 95%CI 2.1-132.9, P = 0.008). In that group, the yield was
      3.1% (95%CI 1.42-5.89). No further cases were detected in the subsequent 2 years.
      CONCLUSION: CXR screening of long-stay prisoners gave a high yield in this study.

PMID- 15971390
TI  - Prevalence of pulmonary tuberculosis and comparative evaluation of screening
      strategies in a Brazilian prison.
AB  - SETTING: A prison (1171 male inmates) in Rio de Janeiro, Brazil. OBJECTIVES: To
      determine the prevalence of active pulmonary tuberculosis (TB) and to assess the
      performance of several screening strategies. DESIGN: In a cross-sectional study,
      all inmates underwent chest radiographic screening. Subjects with abnormal
      findings underwent sputum smear examination and sputum culture. Taking this
      strategy as the reference, we assessed three targeted screening strategies to
      identify TB suspects: Strategy 1: cough >3 weeks; Strategy 2: WHO score > or = 5;
      Strategy 3: presence of at least one potentially TB-related symptom. RESULTS: The
      prevalence of TB cases was 4.6% (48/1052) and 2.7% for definite TB cases. If TB
      suspects identified by targeted screening had sputum smear examination alone, 37
      (86.0%) of the 43 cases would have been missed by Strategy 1, 34/43 (79.1%) by
      Strategy 2 and 34/43 (79.1%) by Strategy 3. If TB suspects had both sputum smear
      examination and, for smear-negative subjects, chest radiography, respectively
      28/43 (65.1%), 18/43 (41.9%) and 13/43 (30.2%) of cases would have been missed.
      CONCLUSION: All three targeted screening strategies were unreliable. Given the
      importance of early TB diagnosis in overcrowded and highly endemic settings,
      routine radiography-based screening may be warranted.

PMID- 15971391
TI  - Speaking the same language: treatment outcome definitions for multidrug-resistant
      tuberculosis.
AB  - SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant
      tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000.
      To address MDR-TB management in the context of the DOTS strategy, the World
      Health Organization and partners have been promoting an expanded treatment
      strategy called DOTS-Plus. However, standard definitions for MDR-TB patient
      registration and treatment outcomes do not exist. OBJECTIVE: To propose a
      standardized set of case registration groups and treatment outcome definitions
      for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus
      strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide,
      a 2-year-long series of meetings, conferences, and correspondence was undertaken
      to review published literature and country-specific program experience, and to
      develop international agreement. RESULTS: Definitions were designed for MDR-TB
      patient categorization, smear and culture conversion, and treatment outcomes
      (cure, treatment completion, death, default, failure, transfer out). Standards
      for conducting outcome analyses were developed to ensure comparability between
      programs. CONCLUSION: Optimal management strategies for MDR-TB have not been
      evaluated in controlled clinical trials. Standardized definitions and cohort
      analyses will facilitate assessment and comparison of program performance. These
      data will contribute to the evidence base to inform decision makers on approaches
      to MDR-TB control.

PMID- 15971392
TI  - The Beijing genotype is a major cause of drug-resistant tuberculosis in
      Kazakhstan.
AB  - SETTING: Nine Kazakhstan oblasts, 2001. OBJECTIVE: To analyse the genetic
      relationship of drug-resistant Mycobacterium tuberculosis strains from Kazakhstan
      and to determine the frequency of the Beijing genotype. DESIGN: All drug
      resistant smear-positive cases identified in nine oblasts during the 2001
      nationwide drug resistance survey were analysed by IS6110 fingerprinting and
      spoligotyping. Isolates were obtained from 150 patients (64 new and 86 retreated
      cases). RESULTS: Eight cases (5.3%) of dual infection were identified. Of the
      remaining 142 strains, 91 (64.1%) were grouped in 18 clusters, indicating a high
      rate of recent transmission of resistant tuberculosis (TB). This was further
      confirmed by the origin of the patients as well as by the similar drug resistance
      patterns of the clustered strains. Accordingly, more than one third of all
      clustered strains were new cases. About 70% of the resistant strains belonged to
      the Beijing genotype, compared to only 37.5% in a control group of 40 susceptible
      isolates. CONCLUSIONS: Transmission of drug-resistant strains seems to contribute
      to the spread of resistant TB in this high incidence region. The Beijing genotype
      should be seen as a major cause of drug-resistant TB in Kazakhstan and was found
      to be associated with drug resistance.

PMID- 15971393
TI  - Deteriorated tuberculosis drugs and management system problems in lower southern
      Thailand.
AB  - SETTINGS: Three institutes, 11 hospitals and 38 community hospitals in southern
      Thailand. OBJECTIVES: To assess the quality of tuberculosis (TB) drugs used in TB
      treatment facilities in southern Thailand and their TB drug management systems.
      DESIGN: Cross-sectional study utilising interviews, document review, inspection
      of drug storage, visual examination of TB drugs, and laboratory analysis of
      samples of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol
      (EMB). RESULTS: No stock-out of TB drugs was found at any level. Thirteen (25%)
      hospitals/institutes removed coated EMB tablets from their foil packages for
      daily dose packing. Eleven (21%) hospitals/institutes bisected 400 mg coated EMB
      tablets before dispensing as a non-available 200 mg tablet. On the day of
      inspection grossly deteriorated EMB was observed in 44% of hospitals/institutes.
      All samples, except 14% of EMB, passed content assay tests. All INH and EMB
      samples passed the dissolution tests, but 62% of RMP samples and 26% of PZA
      samples failed. CONCLUSIONS: Sub-standard deteriorated TB drugs are a serious
      problem for TB control. TB drugs examined in the study area were not managed
      properly. Education on TB drug packaging and storage, and non-destructive systems
      in TB drug distribution, storage, inventory control, quality assurance and
      supervision are essential interventions.

PMID- 15971394
TI  - Transmission trends for human immunodeficiency virus associated tuberculosis in
      New York City.
AB  - SETTING: Since 1992, tuberculosis (TB) control measures have reduced incidence
      rates in New York City and elsewhere. Nevertheless, trends have not been uniform
      in all demographic groups. OBJECTIVE: To characterize the epidemiology of human
      immunodeficiency virus (HIV) associated TB in New York during the 1990s, we
      analyzed social, demographic and clinical characteristics and genetic data on
      Mycobacterium tuberculosis isolates among persons with known HIV-status. DESIGN:
      A retrospective case-control study to compare patients with HIV-associated TB and
      patients with TB alone. RESULTS: Of 546 patients (70.5%) in the Department of
      Health Tuberculosis Control Registry treated for TB, 385 also had documented HIV
      status; 198 were HIV-infected (51%) and 187 (49%) were not. Genotype analysis of
      the 385 M. tuberculosis isolates identified 200 (52%) clustered strains,
      representing recent transmission. Although the overall percentage of TB cases
      associated with restriction fragment length polymorphism (RFLP) clustering fell
      over the period studied, HIV-associated cases were still much more likely to be
      associated with clustering than non-HIV-associated cases. CONCLUSIONS: Continued
      attention is required to contain the spread of TB in this vulnerable population.

PMID- 15971395
TI  - Patterns of tuberculosis risk over time among recent immigrants to Ontario,
      Canada.
AB  - SETTING: Canada receives more than 200000 immigrants annually. Immigrants account
      for 92% of tuberculosis (TB) cases in Toronto, Ontario. Epidemiological profiling
      of recent immigrants is needed to provide more effective TB programs. DESIGN: A
      population-based, retrospective cohort study of recent immigrants to Ontario,
      1990-1997. We generated adjusted rates, risk ratios (RRs), hazard rates since
      arrival, and a complementary log-log model to describe TB risk, compare the
      survival distributions between different sexes, age groups and world regions of
      birth, and determine predictors of disease. RESULTS: TB in recent immigrants was
      23 times (95%CI 20.9-25.5) higher than in Canadian-born, non-aboriginal people.
      Those aged 16-30 and >65 years experienced the highest rates. Sub-Saharan Africa
      had the highest rates for both sexes (RR 95.5, 95%CI 84.3-108.2), followed by
      India and Asia. Hazard rates decreased after arrival, but remained elevated. The
      highest risk was associated with arrival in 1990 and living in Canada <1 year.
      CONCLUSION: Risk for TB varied by region of birth, age at landing and time since
      arrival. Sex was not significant. Persons from sub-Saharan Africa and age >65
      years were the highest risk groups. Risk decreased significantly in the first 1-2
      years after arrival, after which it plateaued.

PMID- 15971396
TI  - Lay health worker intervention with choice of DOT superior to standard TB care
      for farm dwellers in South Africa: a cluster randomised control trial.
AB  - SETTING: Farms in the Boland health district, Western Cape Province, South
      Africa. OBJECTIVE: To evaluate the effect of lay health workers (LHWs) on
      tuberculosis (TB) control among permanent farm workers and farm dwellers in an
      area with particularly high TB prevalence. DESIGN: Pragmatic, unblinded cluster
      randomised control trial. METHODS: This trial measured successful treatment
      completion rates among new smear-positive (NSP) adult TB patients on 106
      intervention farms, and compared them with outcomes in patients on 105 control
      farms. Farms were the unit of randomisation, and analysis was by intention to
      treat. RESULTS: A total of 164 adult TB patients were recruited into the study,
      89 of whom were NSP. The successful treatment completion rate in NSP adult TB
      patients was 18.7% higher (P = 0.042, 95%CI 0.9-36.4) on farms in the
      intervention group than on farms in the control group. Case finding for adult NSP
      TB cases was 8% higher (P = 0.2671) on farms in the intervention group compared
      to the control group. CONCLUSION: Trained LHWs were able to improve the
      successful TB treatment rate among adult NSP TB patients in a well-established
      health service, despite reduction of services.

PMID- 15971397
TI  - Gender and literacy: factors related to diagnostic delay and unsuccessful
      treatment of tuberculosis in the mountainous area of Yemen.
AB  - SETTING: People in the mountainous area of Yemen, having maintained their
      traditional lifestyle, generally believe that uneducated women are unsuccessful
      in using modern medical care. Whether this belief applies to tuberculosis (TB)
      diagnosis and treatment has not been researched in Yemen. OBJECTIVE: To examine
      how gender and literacy influence TB diagnosis and treatment. DESIGN: Individual
      interviews and data collection were conducted for 74 smear-positive pulmonary TB
      patients visiting the National Tuberculosis Institute in Sana'a from December
      2001 to March 2002. The treatment outcome for each patient was checked from
      September 2002 to March 2003. RESULTS: Illiterate patients had a longer
      diagnostic delay than literate patients (P = 0.006, univariate logistic
      regression analysis). They also maintained their traditional view of illness, not
      the illness 'TB'. More females than males completed treatment (P = 0.046,
      univariate logistic regression analysis). Supervision by male relatives
      contributed to completion of treatment among female patients. CONCLUSION: Lack of
      education does not hinder women from receiving TB diagnosis and treatment. The
      concept of traditional illness, however, causes a longer diagnostic delay among
      illiterate patients, and the role of male relatives positively influences
      treatment outcomes for female patients.

PMID- 15971398
TI  - Tuberculosis infection among health care workers in Kampala, Uganda.
AB  - Nosocomial tuberculosis (TB) is a serious problem in sub-Saharan Africa due to
      the absence of protective measures for health care workers (HCWs). To determine
      the prevalence of TB infection among HCWs in Kampala, Uganda, a cross-sectional
      study was conducted between June and August 2001. A tuberculin skin test (TST)
      survey was conducted among 396 HCWs from three hospitals within Kampala, The
      prevalence of TST > or = 10 mm was 57%. Age and department of employment were
      associated with TST > or = 10 mm, while occupation and BCG status were not.
      Health care workers in Kampala, Uganda, have a high prevalence of latent TB
      infection.

PMID- 15971399
TI  - Nosocomial transmission of Mycobacterium tuberculosis in a children's hospital.
AB  - An infant was admitted for evaluation of respiratory distress and tracheomalacia.
      After several weeks of hospitalization, both the infant and her mother were
      diagnosed with culture-positive pulmonary tuberculosis (TB). Sixteen pediatric
      patients and 293 health care workers were evaluated for exposure to Mycobacterium
      tuberculosis. Tuberculin skin test conversions occurred in 6.7% of patients and
      1.9% of pediatric health care workers. While nosocomial transmission of TB is
      relatively rare in children's hospitals, this report highlights the differences
      between TB control efforts in pediatric vs. adult facilities, including the
      importance of screening the adult visitors of children admitted with suspected
      TB.

PMID- 15971400
TI  - Short-course chemotherapy for paediatric respiratory tuberculosis: 5-year report.
AB  - This report presents the 5-year follow-up of 137 children with respiratory
      tuberculosis enrolled in a randomised clinical trial of two different anti
      tuberculosis regimens 9HR and 2HRZ3/4RH2. Both regimens had similar cure rates,
      with low relapse rates and mortality. Of 134 children followed up to 5 years, 86%
      had normal radiographs, with more sequelae in the 9HR group (15% vs. 1.5%, P <
      0.01). One patient relapsed and there was one accidental death. Short-course
      chemotherapy in children is safe, effective and well tolerated, and leads to
      excellent long-term results, with a small proportion of children left with
      radiological sequelae.

PMID- 15971401
TI  - Plasma pooling: utility in expediting bioequivalence assessment of rifampicin
      containing fixed-dose combinations.
AB  - To improve the rapidity of the registration process of rifampicin (RMP)
      containing fixed-dose combination (FDC) formulations, a plasma pooling
      methodology was used to increase the throughput of bioanalysis of plasma samples
      from bioequivalence trials of FDCs. Plasma samples of a biostudy were analysed
      for RMP using traditional analysis methods as well as a plasma pooling method
      (volunteer and time pooling). Both methods produced similar results, with less
      than 15% variability in both volunteer and time pooling. The plasma pooling
      method for bioanalysis was validated. Further studies are required to identify
      and reduce the percentage variability.

PMID- 15971402
TI  - Will the bleach method keep its promise in sputum smear microscopy?

PMID- 15971403
TI  - Novel anti-tuberculosis FDC formulations without reduced bioavailability of
      rifampicin: from concept to market.

PMID- 15971404
TI  - Fatal pulmonary haemorrhage from a mycotic pulmonary artery aneurysm.

PMID- 15971405
TI  - Partial intestinal obstruction due to clofazimine in a patient with multidrug
      resistant tuberculosis.

PMID- 15971407
TI  - Seasonality of tuberculosis.

PMID- 15971406
TI  - Molecular methods needed for the accurate assessment of Mycobacterium bovis
      infection.

PMID- 15971408
TI  - Passive smoking and respiratory health in children and adults.

PMID- 15971409
TI  - Dietary fructose: implications for dysregulation of energy homeostasis and
      lipid/carbohydrate metabolism.
AB  - Fructose intake and the prevalence of obesity have both increased over the past
      two to three decades. Compared with glucose, the hepatic metabolism of fructose
      favors lipogenesis, which may contribute to hyperlipidemia and obesity. Fructose
      does not increase insulin and leptin or suppress ghrelin, which suggests an
      endocrine mechanism by which it induces a positive energy balance. This review
      examines the available data on the effects of dietary fructose on energy
      homeostasis and lipid/carbohydrate metabolism. Recent publications, studies in
      human subjects, and areas in which additional research is needed are emphasized.

PMID- 15971410
TI  - Formation and human risk of carcinogenic heterocyclic amines formed from natural
      precursors in meat.
AB  - A group of heterocyclic amines that are mutagens and rodent carcinogens form when
      meat is cooked to medium and well-done states. The precursors of these compounds
      are natural meat components: creatinine, amino acids, and sugars. Defined model
      systems of dry-heated precursors mimic the amounts and proportions of
      heterocyclic amines found in meat. Results from model systems and cooking
      experiments suggest ways to reduce their formation and, thus, reduce human
      intake. Human cancer epidemiology studies related to the consumption of well-done
      meat products are listed and compared in this review.

PMID- 15971411
TI  - The mechanism and regulation of fat mobilization from adipose tissue: desnutrin,
      a newly discovered lipolytic enzyme.
AB  - A new member of a family of proteins functioning in the regulation of lipolysis
      in adipose tissue has been discovered and named "desnutrin." Desnutrin is
      transiently induced by fasting and decreased by re-feeding. A close homolog,
      termed adiponutrin, has the opposite expression pattern, being induced by feeding
      and disappearing upon fasting. Desnutrin functions by acting as the first enzyme
      in lipolysis, hydrolyzing triglycerides to diglycerides, whereas the well-known
      hormone-sensitive lipase takes the diglycerides to monoglycerides and on to free
      fatty acids.

PMID- 15971412
TI  - Science, law, and politics in the Food and Drug Administration's genetically
      engineered foods policy: FDA's 1992 policy statement.
AB  - The US Food and Drug Administration's (FDA's) 1992 policy statement was developed
      in the context of critical gaps in scientific knowledge concerning the
      compositional effects of genetic transformation and severe limitations in methods
      for safety testing. FDA acknowledged that pleiotropy and insertional mutagenesis
      may cause unintended changes, but it was unknown whether this happens to a
      greater extent in genetic engineering compared with traditional breeding.
      Moreover, the agency was not able to identify methods by which producers could
      screen for unintended allergens and toxicants. Despite these uncertainties, FDA
      granted genetically engineered foods the presumption of GRAS (Generally
      Recognized As Safe) and recommended that producers use voluntary consultations
      before marketing them.

PMID- 15971413
TI  - Are enterobacterial common antigens involved in the etiology of rheumatoid
      arthritis?

PMID- 15971414
TI  - In early rheumatoid arthritis the combination of methotrexate and infliximab over
      2 years reduces the progression of radiological lesions more than methotrexate
      alone.

PMID- 15971415
TI  - Hormone concentrations in synovial fluid of patients with rheumatoid arthritis.
AB  - OBJECTIVE: Alterations in local concentrations of hormones, affecting directly
      synovial cells, could be involved in the modulation of the rheumatic inflammatory
      processes. The aim of present study was to investigate the levels of selected
      hormones (steroids, peptide and thyroid hormones) in synovial fluid of knee joint
      of patients with rheumatoid arthritis (RA) and control individuals with non
      rheumatic exudate (with osteoarthrosis, OA). METHODS: Thirty-eight patients, 22
      female and 16 males, with rheumatoid arthritis (RA) and 12 subjects with
      osteoarthrosis (OA, control group, 6 females and 6 males) participated in the
      study. Concentrations of cortisol (CS), 17-beta-estradiol (ES),
      dehydroepiandrosterone (DHEA), progesterone (PRG), aldosterone ALD), prolactin
      (PRL), insulin (INS), and C-peptide were determined by radioimmunoassay in
      synovial fluid. Insulin binding to isolated cell membrane of cells from synovial
      sediment was estimated by using radioiodine labeled insulin. In a group of
      patients (10 with RA and 4 with OS), the levels of free threeiodothyronine (FT3),
      TSH and growth hormone (GH) were also determined in synovial fluid. RESULTS:
      Increased levels of ES in synovial fluid of RA patients were observed, and higher
      differences were noted in men. TE concentrations were moderately elevated in
      synovial fluid of RA patients, however the ratio of ES/TE was significantly
      higher in male RA compared to OA patients. Higher levels of PRG, ALD and growth
      hormone were noted in synovial fluid of RA patients. Besides the steroid hormones
      the presence of insulin and C-peptide was noted in synovial fluid and the
      correlation between the levels of these two peptides was highly significant. The
      concentrations of INS and C-peptide in synovial fluid of patients from RA and OA
      group were not significantly different, however, highly significant increase of
      insulin binding to isolated membrane of synovial cells was found. Concentrations
      of cortisol, dehydroepiandosterone, prolactin, TSH and FT3 in synovial fluid were
      not significantly different in RA and OA groups. CONCLUSIONS: Besides the
      steroids also insulin, c-peptide, GH and FT3 were found in synovial fluid. The
      elevated ALD and GH levels in synovial fluid of RA patients and the presence of
      INS in synovial fluid with increase of INS binding to plasma membranes of cells
      from synovial fluid of RA patients suggest that besides the gonadal steroids also
      these hormones may affect the local inflammatory processes.

PMID- 15971416
TI  - Evaluation of abnormalities of orthostatic postural control in systemic
      sclerosis.
AB  - OBJECTIVE: Systemic sclerosis (SSc) is a multi-systemic disease of unknown
      etiology characterized by damage to the small arteries, arterioles and
      capillaries. The documented occurrence of various neuropathies in SSs patients
      led us to hypothesize that there is a potential for postural control impairments
      in such disease. This study was aimed at evaluating the orthostatic postural
      control of SSc patients who do not manifest balance or hearing symptoms. METHODS:
      Postural stability was assessed in 36 female SSc patients by means of a static
      computerized posturography technique. Their immunological and microvascular
      condition were evaluated by means of blood tests and microcapillaroscopy of the
      digital vessels. Posturography and microcapillaroscopy were performed before and
      after treating the patients with Iloprost. In order to compare results,
      posturography was also carried out on a control group composed of 10 healthy
      women of similar age. Both groups were studied in two different sensory
      conditions, i.e. with eyes opened and with eyes closed. RESULTS: Posturography
      results showed relevant differences in body sway between patients and control
      subjects. Fourier spectral analysis of body sway showed that, independently from
      visual control, SSc patients exhibit a higher level of low/middle frequency
      oscillations (both on the lateral and the anteroposterior axis). No relationship
      was established between disease stage and postural performance. CONCLUSION: This
      study seems to indicate a subtle neurophysiological dysfunction in the
      orthostatic postural control of female SSc patients. Further tests on the
      somatosensory neurological function of SSc patients may help support the above
      mentioned findings.

PMID- 15971417
TI  - Diagnostic value of serum and synovial procalcitonin in acute arthritis: a
      prospective study of 42 patients.
AB  - OBJECTIVE: To determine the diagnostic value of serum and synovial procalcitonin
      (PCT) for bacterial arthritis and to determine the cellular origin of synovial
      PCT. METHODS: A prospective study enrolled 42 patients with acute arthritis
      including 11 bacterial arthritis, 18 rheumatoid arthritis and 13 crystal induced
      arthritis. Diagnostic values of serum and synovial PCT levels were determined by
      a immunoluminometric assay (Lumitest PCT) and compared to those of classical
      inflammatory markers (C-reactive protein, erythrocyte sedimentation rate,
      synovial fluid cellularity and both serum and synovial IL-6 and TNF alpha). Using
      fibroblast-like synoviocyte (FLS) cultures derived from rheumatoid arthritis (n =
      4) and osteo-arthritis (n = 3) synovium, with or without stimulation by
      lipopolysaccharid or recombinant streptococcal protein 1/II, we attempted to
      determine whether synovial cells could be a source of PCT. RESULTS: Serum PCT was
      the best parameter to distinguish patients with acute bacterial arthritis from
      patients with crystal induced arthritis or rheumatoid arthritis. In setting of an
      acute arthritis serum PCT (> 0.5 ng/mL) achieved 55% sensitivity and 94%
      specificity for the diagnosis of bacterial arthritis, while CRP (> 50 mg/L) had
      100% sensitivity but poor specificity (40%). Serum PCT appeared to be higher in
      patients with septic arthritis resulting from "systemic infection" than in cases
      resulting from direct inoculation. Synovial PCT was not useful to discriminate
      between infectious and non infectious arthritis in clinical practice. PCT could
      not be detected at significant levels in the conditioned medium from fibroblast
      like synoviocyte cultures. CONCLUSION: Serum PCT is a poorly sensitive but
      specific marker of bacterial arthritis. Use of serum PCT in association with CRP
      could nevertheless be useful in an emergency situation for the diagnosis of
      bacterial arthritis.

PMID- 15971418
TI  - Differential expression of chemokines in synovial cells exposed to different
      Borrelia burgdorferi isolates.
AB  - OBJECTIVE: Lyme borreliosis is characterized by strong inflammatory reactions
      probably due to the presence of Borrelia burgdorferi in the joint. It has been
      suggested that Borrelia induces the immunological mechanisms that either can
      amplify the inflammatory response or can suppress it. To reveal the underlying
      mechanisms of chemoattraction and activation of responding leukocytes, we
      investigated the induction of chemokines in human synoviocytes exposed to two
      different B. burgdorferi sensu stricto isolates (strain Geho and B31). METHODS:
      Synoviocytes were exposed in vitro up to 5 days. Semiquantitative reverse
      transcription polymerase chain reaction (RT-PCR) was used to assess the relative
      chemokine mRNA expression of RANTES/CCL5, SDF-1alpha/CXCL12 alpha, SDF
      1beta/CXCL12 beta, MCP-1/CCL2, MCP-2/CCL8, IL-8/CXCL8 and MIP-1alpha/CCL3, and
      enzyme-linked immunosorbant assay (ELISA) was used to assess the protein
      expression of RANTES, SDF-1, MCP-1, and MIP-1alpha in the culture supernatant.
      RESULTS: MCP-1 gene expression was not changed by strain B31 but MCP-1 gene
      expression along with protein concentration was suppressed by strain Geho. Both
      strains induced RANTES mRNA and protein concentration. SDF-1 gene expression was
      suppressed, whereas protein concentrations were unchanged by both strains. IL-8
      gene expression was unchanged by using strain Geho but significantly upregulated
      by strain B31. Both strains induced MCP-2 mRNA expression. MIP-1alpha mRNA
      expression was induced, but chemokine concentration was suppressed by both
      strains. CONCLUSION: This study suggests that the orchestra of chemokines plays
      an important role in the immunopathogenesis of early Lyme arthritis.

PMID- 15971419
TI  - Inhibition of NF-kappaB signaling by fenofibrate, a peroxisome proliferator
      activated receptor-alpha ligand, presents a therapeutic strategy for rheumatoid
      arthritis.
AB  - OBJECTIVES: Inflammatory mediators such as interleukin-6 and tumor necrosis
      factor-alpha play an important role in the pathogenesis of rheumatoid arthritis
      (RA) by promoting chronic inflammation and joint damage. NF-kappaB is a
      transcriptional activator of genes for these cytokines. It also plays an
      important role in the regulation of osteoclast differentiation which plays a key
      role in joint destruction in RA. Ligands for peroxisome proliferator-activated
      receptor (PPAR) -gamma have recently been reported to inhibit the development of
      RA. In this study, we investigated the role of PPARalpha in RA. METHODS: We
      analyzed the protein expression of PPAR-alpha and -gamma in rheumatoid synovial
      fibroblasts (RSF) from RA patients and analyzed the effects of ligands for PPAR
      alpha and -gamma on cytokine production from RSF NF-kappaB activations in RSF and
      osteoclast differentiation from osteocalst progenitor in the peripheral blood.
      Moreover, we analyzed the effects of oral administration of PPAR-alpha and -gamma
      ligands on the development of adjuvant-induced arthritis (AIA) in female Lewis
      rats. RESULTS: We confirmed the expression of PPAR-alpha in RSF and also
      demonstrated that fenofibrate, a ligand for PPAR-alpha, inhibited cytokine
      production from RSF, NF- kappaB activation in RSF, and osteoclast differentiation
      from osteoclast progenitor cells. Furthermore, we demonstrated that fenofibrate
      inhibits the development of arthritis in a rat model of human RA. CONCLUSIONS:
      These results indicate that fenofibrate suppresses the development of arthritis
      by inhibition of NF-kappaB signaling; therefore, this compound offers possible
      anti-rheumatic drug.

PMID- 15971420
TI  - Cervical spine involvement in longstanding ankylosing spondylitis.
AB  - OBJECTIVE: To investigate the degree of ossification and the frequency of
      ankylosis between the atlas and the dens of the axis in patients with
      longstanding ankylosing spondylitis (AS), to assess radiological involvement of
      the cervical spine, and to determine their correlations with structural severity
      and clinical variables, including neurological abnormalities. METHODS: In 61 AS
      patients with disease duration over 7 years, the findings of conventional
      radiographs were graded by the Bath Ankylosing Spondylitis Radiology Index
      (BASRI), and the ossification levels between the atlas and the dens and the
      severity of zygapophyseal (ZA) joint lesions were scored using multislice CT.
      Neurological examinations and somatosensory evoked potentials (SSEP) were
      performed by neurologists. RESULTS: According to the BASRI, 50 patients (82.0%)
      had radiological changes of the cervical spine > or = score 1. Thirty-seven
      patients (60.6%) revealed a certain extent of the atlantodental ossification, and
      the presence of partial or complete atlantodental ankylosis was seen over 30% of
      the patients. The BASRI-cervical spine score and the atlantodental ossification
      levels correlated with disease duration. ZA involvement was observed in 49
      patients (80.3%), including 23 with ZA fusion (37.7%). Although 4 of 11 patients
      with atlantoaxial subluxation showed abnormal SSEP none had significant
      neurological complications. This might be attributed in part to atlantodental
      ankylosis and ZA fusion. Finally, ossifications of the anterior and posterior
      longitudinal ligaments were found 26.2 and 29.5%, respectively. CONCLUSION:
      Cervical spine involvement and atlantodental ossification or ankylosis appear to
      be common in patients with longstanding AS, and to be particularly more severe in
      patients with a longer disease duration.

PMID- 15971421
TI  - Lack of association between TNF-308 polymorphism and the clinical and
      immunological characteristics of systemic lupus erythematosus and primary
      Sjogren's syndrome.
AB  - OBJECTIVE: To investigate the previously reported association of tumor necrosis
      factor alpha (TNF) -308 single nucleotide polymorphism (SNP) with the clinical
      course and immunological features in patients with systemic lupus erythematosus
      (SLE) and primary Sjogren's syndrome (pSS). METHODS: The studied group consisted
      of 113 consecutive SLE and 65 pSS patients. TNF -308 SNP was determined by the
      polymerase chain reaction-restriction fragment length polymorphism technique.
      Clinical and immunological characteristics were assessed according to a standard
      protocol that included disease activity (SLEDAI) and damage (SLICC Damage Index).
      Serum TNFalpha levels were measured in samples collected from 32 patients with
      SLE and 16 with pSS by enzyme-linked immunosorbent assay. RESULTS: The TNF2
      allele (A) was observed in 46% and 54% of SLE and pSS patients, respectively. We
      failed to find any significant association between the -308 SNP and disease
      manifestations, the presence of autoantibodies or cytokine levels in either
      group. CONCLUSION: TNF -308 SNP (TNF2) does not exhibit a significant influence
      on the disease course or immunological response in SLE and pSS. Other genetic
      and/or environmental factors seem to be required and to be more important than
      TNF2 allele for the progression of these diseases.

PMID- 15971422
TI  - Inactivation of xanthine oxidoreductase is associated with increased joint
      swelling and nitrotyrosine formation in acute antigen-induced arthritis.
AB  - OBJECTIVE: Arthritis is associated with increased articular formation of
      nitrotyrosine, which may contribute to injury. Nitrotyrosine is formed by
      nitration of tyrosine by reactive nitrogen species such as peroxynitrite, the
      formation of which may be enhanced by xanthine oxidoreductase (XOR), since it can
      generate nitric oxide from nitrite/nitrate, and superoxide during xanthine
      metabolism. We hypothesized that inactivation of XOR would protect against
      antigen-induced arthritis (AIA) and decrease nitrotyrosine formation. METHODS:
      AIA was induced with methylated bovine serum albumin (mBSA) in three groups of
      Wistar rats: animals fed on (1) tungsten-enriched chow (0.7 g/kg) (TG), which
      inactivates XOR, (2) standard chow (SG), and (3) rats treated with allopurinol
      (50 mg/kg/day; p.o.) (AG). Nitrotyrosine in patella-synovium was quantified by
      mass spectrometry three weeks after intra-articular (i.a.) antigen injection.
      RESULTS: Treatment with tungsten, but not allopurinol, suppressed plasma and
      articular XOR activity at < or = 0.9% of normal levels. XOR inactivation was
      associated with increased knee swelling 24-48 hrs post i.a. mBSA, compared with
      controls (mean increase +/- SEM of knee diameter from baseline of 3.3 +/- 0.5,
      2.0 +/- 0.3 and 1.9 +/- 0.2 mm in TG, SG and AG (n = 14 each group),
      respectively; p < 0.05, TG vs SG, ANOVA). Mean ratio of articular nitrotyrosine
      tyrosine (+/- SEM) was increased in the XOR-inactivated group, compared with
      controls: 12.3 +/- 0.7, 9.6 +/- 0.8 and 10.4 +/- 0.5 pg/microg in TG, SG and AG,
      respectively; p < 0.05, TG vs SG. CONCLUSION: Contrary to expectation, XOR
      inactivation was associated with increased joint swelling and articular tyrosine
      nitration in acute AIA, suggesting a novel, protective role for XOR in
      inflammatory arthritis.

PMID- 15971423
TI  - Influence of clinical and immunological parameters on the health-related quality
      of life of patients with primary Sjogren's syndrome.
AB  - OBJECTIVE: To evaluate health-related quality of life (HR-QoL) in patients with
      primary SS patients using the SF-36 questionnaire and to analyse the association
      between the main clinical features and the SF-36 scales. METHODS: We studied 110
      patients (105 women and 5 men, mean age of 56 years) with primary SS seen
      consecutively in the outpatient clinic of our Department. We used the population
      based reference values for the Spanish version of the SF-36 health survey as
      control values for a healthy population. RESULTS: Comparison between patients
      with primary SS and the control population showed lower scores in all SF-36
      scales (p < 0.001). Analysis of the SF-36 scales by gender showed a significant
      correlation between age and the values for physical functioning (p = 0.013) and
      bodily pain (p = 0.016) scores. No significant differences in SF-36 scores were
      found when comparing patients according to the presence or absence of sicca
      features. Women with vaginal dryness had lower scores for social functioning
      (61.9 vs. 74.4) and general health (37.2 vs. 44.7) than those without, although
      the differences were not statistically significant (p > 0.05). Patients with
      extraglandular involvement had lower scores for the vitality scale (40.8 vs. 54.5
      p = 0.007), social functioning (67.0 vs. 79.8, p = 0.010), bodily pain (49.5 vs.
      62.5, p = 0.018) and general health (38.6 vs. 49.4 p = 0.001) than those without.
      CONCLUSION: Patients with primary SS had clearly lower HR-QoL scores than the
      healthy population; with significantly lower scores in all SF-36 scales and in
      both summary measures. We identified several epidemiological and clinical SS
      features related to these lower SF-36 scores. Age at protocol correlated with
      physical functioning and bodily pain. Vaginal dryness was the sicca feature that
      most affected the HR-QoL of female SS patients, and a poor HR-QoL was also
      observed in those patients with a systemic expression of the disease, with
      pulmonary involvement being the extraglandular manifestation that most
      contributed to a poor HR-QoL. Our results highlight the importance of earlier
      diagnostic and therapeutic management of patients with primary SS, which,
      together with a close follow-up, may contribute to a significant improvement in
      their HR-QoL.

PMID- 15971424
TI  - Diagnosis delay in familial Mediterranean fever (FMF): social and gender gaps
      disclosed.
AB  - OBJECTIVE: To characterize the factors contributing to a greater than 10 year
      delay in the diagnosis of familial Mediterranean fever (FMF). METHODS: 50
      patients, in whom diagnosis of FMF was delayed by more than 10 years, comprised
      the study population. The clinical, demographic and molecular genetic
      characteristics were compared to a control group of 50 FMF patients, in whom the
      diagnosis was made within a reasonable time period (less than 5 years from
      onset). Additional factors contributing to a delayed diagnosis in the study
      group, including physician-related factors, patient-related factors, disease
      factors and other factors, were studied as well. RESULTS: Overall, attack sites,
      duration and severity were comparable among study and control groups. No
      differences in ethnic origin or family history of FMF were noted between the
      groups. There were significantly more females (p = 0.009), newly-arrived
      immigrants (p = 0.005) and carriers of unidentified MEFV mutations (p = 0.04) in
      the study group. Delayed diagnosis of FMF stemmed from misdiagnosis and physician
      negligence (70%), as well as from patient negligence (70%). The diagnosis was
      ultimately made mainly due to a change in disease pattern and other causes, such
      as diagnosis of FMF in a relative. CONCLUSION: The study unveils unexpected
      causes behind a prolonged delay in the diagnosis of FMF such as social status
      (immigrant), female gender, physician negligence and lack of patient awareness.
      The possibility that the delay stems from a milder disease pattern was dismissed.

PMID- 15971425
TI  - Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern
      of invasive tumor-like cells.
AB  - OBJECTIVE: In rheumatoid arthritis (RA) the synovial membrane proliferates and
      invades the underlying tissues. The cell-associated fibrinolytic system
      (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen
      activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation.
      For this reason, the expression and the role of such enzymatic system was
      investigated in synovial fibroblasts (SF) of normal and RA patients. METHODS: In
      SF obtained from RA patients and control subjects, uPA, uPAR and PAI-1 were
      measured by ELISA of cell lysates and culture medium and by RT-PCR of mRNAs. uPA
      was also studied by zymography. Proliferation was measured by cell counting and
      cell invasion with the Boyden chamber. RESULTS: RA-SF over-express uPAR and PAI-1
      and are more prone than the normal counterpart to spontaneous and uPA-challenged
      invasion and proliferation, which are counteracted by antagonists of the
      fibrinolytic system. CONCLUSIONS: RA-SF display the fibrinolytic pattern and
      behaviour of invasive tumor-like cells. Antagonists of the fibrinolytic system
      are able to revert growth and invasion of both normal and RA-SF.

PMID- 15971426
TI  - Use of air-steroid-saline mixture as contrast medium in greyscale ultrasound
      imaging: experimental study and practical applications in rheumatology.
AB  - OBJECTIVES: To investigate experimentally the echogenicity of air, a steroid
      suspension and physiological saline mixed with water in order to find the best
      contrast medium for injections. To show the practical applications of an
      airsteroid-saline mixture as a contrast medium in rheumatology. METHODS: In
      vitro. First, quality assurance measurements were conducted twice on the
      ultrasound (US) equipment. Subsequently air, a steroid suspension, or
      physiological saline mixed with water, first alone and then in different
      combinations, were examined with US using quantitative image analysis. Clinical.
      The effectiveness of an air-steroid-saline mixture as contrast medium in
      ultrasonography was tested in joint, bursa and tendon sheath injections. RESULTS:
      In vitro. Based on the quality assurance measurements the physical performance of
      the US equipment was excellent. Verified visually and quantitatively the mixture
      of air, steroid and saline produced the best contrast on US. The importance of
      air bubbles producing contrast was obvious. Clinical application. Firstly,
      visualisation of the contrast medium with US made it possible to follow in real
      time the passage of a drug to the target area. Secondly, the use of the contrast
      method verified the presence of steroid in the synovial target intended after a
      blind injection. Thirdly, anatomical and pathologic anatomical connections could
      be visualized using this contrast medium in the wrist, shoulder, knee, ankle and
      foot joint CONCLUSIONS: Verification of US system performance by quality
      assurance measurement is essential for US imaging. The air-steroid-saline
      contrast medium method of ultrasound scanning is a somewhat invasive, but
      inexpensive and rapid method. It can verify the existence or non-existence of an
      air-steroid-saline contrast medium in the desired place and in adjacent
      structures, thus showing possible pathologic anatomic connections. The method has
      a diagnostic and therapeutic value, and expands the interventional spectrum of
      sonographic imaging.

PMID- 15971427
TI  - RANTES promoter polymorphism as a genetic risk factor for rheumatoid arthritis in
      the Chinese.
AB  - OBJECTIVES: There is increasing evidence suggesting a role of RANTES in the
      pathogenesis of rheumatoid arthritis (RA) and we evaluated the possible effect of
      RANTES gene on the susceptibility to RA in Chinese patients. METHODS: We examined
      the polymorphisms at the promoter positions -28 and -403 of this gene in 151
      Chinese RA patients and 149 ethnically matched healthy controls. RESULTS: The
      genotypic frequencies in this study were in Hardy-Weinberg equilibrium. RA
      patients had significantly higher frequencies of the A allele (36.1% vs. 27.5%, p
      = 0.024) and A/A genotype (odds ratio [OR] = 3.3, 95% confidence interval [CI] =
      1.4-7.9, p = 0.005) at the promoter -403 position. Differences in allele and
      genotype frequencies at the promoter -28 position between patients and controls
      were not statistically significant (for G allele, p = 0.103 and for genotype, p =
      0.106). RA patients also had a significantly higher frequency of the -28 C/G with
      -403 A/A compound genotype (OR = 4.6, 95% CI = 1.5-14.5, p = 0.005), and a higher
      frequency of the -28 G/-403 A haplotype with marginal statistical significance
      (OR = 1.7, 95% CI = 1.0-3.1, p = 0.059). CONCLUSION: Our results indicate that
      polymorphism in the promoter region of RANTES gene is associated with the
      susceptibility to RA in the Chinese population.

PMID- 15971428
TI  - Assessment of changes due to the long-term effect of estrogen and calcium
      deficiency in the trabecular bone structure in rats.
AB  - OBJECTIVE: To assess structural changes, especially structural anisotropy, of rat
      bone trabecular system 6 months after ovariectomy followed by low-calcium diet.
      METHOD: The study was carried out on the group of 32 female rats, half of which
      were ovariectomized at the age of 75 days. The animals were divided into 4
      groups: one receiving a normal diet (N), another receiving a low-calcium diet
      (LCa), ovariectomized rats receiving a normal diet (OVX), and ovariectomized
      animals receiving a low-calcium diet (OVX+LCa). After 6 months the animals were
      killed, bone specimens were collected and cut into sections of 6 microm
      thickness. Digital images of the sections were analyzed using a software package
      enabling analysis of the transversal and longitudinal trabeculae. RESULTS:
      Significant changes in trabecular structure due to a low-calcium diet (trabecular
      bone volume loss of 19%), ovariectomy (53%) and ovariectomy combined with low
      calcium diet (71%) were observed. In all the analyzed groups, the percentage loss
      (as compared with controls) of transversal trabeculae was more significant than
      the loss of longitudinal trabeculae. In the LCa group, transversal trabecular
      loss was 39%, longitudinal 25%, in (Ovx): 63% and 54%, respectively, and in OVX +
      LCa: 77% and 72%. The structural anisotropy coefficient, defined as the ratio of
      transversal to longitudinal trabecular surface area was 0.64 for (N), 0.50 for
      LCa, 0.49 for OVX, and 0.54 for OVX+LCa groups. CONCLUSIONS: The effect of
      ovariectomy and low-calcium diet on trabecular structure can be assessed
      quantitatively by means of analysis of transversal and longitudinal trabeculae
      associated with the main direction of strain. The degree of transversal
      trabecular loss is much higher than the longitudinal trabecular loss; the
      difference becomes smaller with the progress of bone destruction, being greatest
      in the LCa group, the smallest in the (OVX+ LCa) group.

PMID- 15971429
TI  - Increased frequency of ultrasonographic findings suggestive of renal stones in
      patients with ankylosing spondylitis.
AB  - OBJECTIVE: To determine the frequency of hypercalciuria and renal stones in
      ankylosing spondylitis (AS) sufferers. METHODS: This study involved 83
      consecutive AS patients (21 female, 62 male; mean age 36.7 yr), 72 consecutive
      Behcet's disease (BD) patients (29 female, 43 male; mean age 37.7 yr) as disease
      control and 92 healthy control (HC) (26 female, 66 male; mean age 32.9 yr.)
      Twenty-four hour urine analyses for urinary calcium and uric acid levels were
      performed in each patient. Likewise, blood samples for erythrocyte sedimentation
      rate (ESR), C-reactive protein (CRP), parathyroid hormone (PTH), calcium and uric
      acid evaluation were taken. Renal ultrasonography to evaluate the presence of
      renal stone was performed in patients with AS, as well as in the BD patients and
      HC individuals after a fasting period of 12 hours. RESULTS: 20 of the 80 (25%)
      patients with AS were diagnosed with renal stones. Only 4/72 (5.5%) BD patients,
      and 3/98 (3.3%) HC individuals had renal stones by ultrasonography. AS patients
      had a significantly higher frequency of renal stones compared with BD (p < 0.001)
      and HC (p < 0.0001). AS patients with renal stones were much older and their
      disease duration was much longer in comparison with AS patients without renal
      stones. Ultrasonographic and laboratory findings did not correlate. The number of
      AS patients with hypercalciuria who had renal stones was higher than that of AS
      patients who did not have renal stones (p < 0.01). There was a negative
      correlation between acute phase response and spinal mobility. CONCLUSION: Renal
      stone prevalence was found to increase in AS patients. The likelihood of renal
      stone formation was also found to increase with the extension of the disease
      duration of AS sufferers.

PMID- 15971430
TI  - Skin manifestations of systemic lupus erythematosus refractory to multiple
      treatment modalities: poor results with mycophenolate mofetil.
AB  - OBJECTIVE: Skin disease can be one of the most refractory clinical manifestations
      of systemic lupus erythematosus (SLE). The standard therapy consists of
      sunscreens, topical corticosteroids and antimalarials. However in difficult cases
      a variety of other drugs have been tried. Here we describe our clinical
      experience with mycophenolate mofetil (MMF) in patients with cutaneous
      manifestations of SLE. METHODS: Seven patients with SLE and skin involvement
      (including acute cutaneous lupus, subacute cutaneous lupus, discoid lupus
      erythematosus, vasculitis, urticarial rash and chilblain lupus) who had received
      treatment with MMF were included. The clinical characteristics,
      serologicalfindings and response to treatment were recalledfrom retrospective
      review of the files. RESULTS: Our results showed no response in 5 patients,
      partial response in 1 patient and initial response but skin flare whilst on MMF
      in 1 patient. The median dose of MMF was 2 g (range 2-3 g). Adverse events on MMF
      were mild, mainly gastrointestinal and occurred in 5 patients. No patients
      discontinued MMF due to adverse events. CONCLUSIONS: MMF appears not to be
      particularly effective in the treatment of skin disease in SLE. It should be
      noted that our group of patients had previously failed to respond to a median of
      4 (range 2-10) different drugs used to treat SLE skin disease. Thus, the patients
      in the study could be considered at the severe end of skin disease spectrum.

PMID- 15971431
TI  - Evaluation of the European Spondyloarthropathy Study Group (ESSG) classification
      criteria in a Chinese population.
AB  - OBJECTIVE: To evaluate for thefirst time in a Chinese population, the usefulness
      of the European Spondyloarthropathy Study Group (ESSG) criteria. METHODS: A total
      of 193 clinically diagnosed SpA patients were compared to 166 patients with other
      types of arthritis, using the parameters listed in the ESSG criteria. RESULTS:
      The sensitivity and specificity of the ESSG criteria in this Chinese population
      were high at 85.4% and 96.4% respectively. CONCLUSION: The use of ESSG criteria
      for classifying SpA in Chinese will not lead to significant omission of SpA
      patients or inclusion of patients who do not have SpA.

PMID- 15971432
TI  - Successful treatment of osteolytic epithelioid hemangioendothelioma with
      pamidronate.
AB  - We describe the case of a 70-year-old man with unicentric grade 1 epitheloid
      hemangioendothelioma (EH) of the bone that favourably responded to intravenous
      pamidronate as a single agent. After 6 years of follow-up, the patient was in
      complete remisssion. We suggest that use of bisphosphonates should be considered
      in the treatment of osteolytic EH.

PMID- 15971433
TI  - Successful therapy of bosentan-refractory pulmonary arterial hypertension (PAH)
      with inhalative iloprost.
AB  - Pulmonary arterial hypertension (PAH) is a severe complication of systemic
      sclerosis. High vascular resistance in PAH arises from an imbalance between
      vasodilatory mediators (prostacyclin, NO) and vasoconstrictive mediators
      (endothelin, thromboxane A-2). Inhaled iloprost and the dual endothelin receptor
      antagonist bosentan have recently been shown to be effective in controlled
      clinical trials. Our case report demonstrates that patients with bosentan
      refractory PAH can be successfully treated with iloprost inhalation.

PMID- 15971434
TI  - Is there a rationale to using leflunomide in early rheumatoid arthritis?
AB  - The efficacy of leflunomide in the treatment of early rheumatoid arthritis (RA)
      patients might be attributed to the fact that it acts at several levels,
      including the anti-inflammatory and anti-destructive pathways. This is in
      addition to its inhibition of the L-dihydro-orotate dehydrogenase (DHOH) enzyme
      and pyrimidine de novo synthesis which decreases cell proliferation and more
      specifically early activated CD4+ T cells, as well as monocyte interaction with T
      cells leading to cytokine and anticytokine production. Recent studies clearly
      indicate the rationale of an early administration of leflunomide in RA patients,
      particularly in the light of the results of previously reported clinical studies
      showing its rapid onset of action when compared to other DMARDs. The early
      efficacy and safety of leflunomide in patients with early RA is sustained over a
      long period, and the long-term safety profile of leflunomide does not seem to be
      different from that observed in phase III trials.

PMID- 15971435
TI  - Joint hypermobility: the use of a new assessment tool to measure lower limb
      hypermobility.
AB  - OBJECTIVES: The aim of the study was to compare the use of a new assessment tool
      for diagnosis of hypermobility in the lower limb to the Beighton score for
      generalised hypermobility. METHODS: Three groups of children were compared (n =
      225) and included a "normal" population of 116 school children, a "possible
      hypermobile" group of 88 children attending afoot and gait clinic and a "known
      hypermobile" group of 21 children referred from a paediatrician or
      rheumatologist. The Beighton score was used to measure generalised hypermobility.
      The Lower Limb Assessment Score was used to measure hypermobility in the lower
      limbs. RESULTS: The Lower Limb Assessment Score was able to distinguish between
      the three groups of children better than the Beighton score. At a threshold of
      5/9 indicating hypermobility, the Beighton score identified hypermobility in 34%
      of school children; the lower limb score identified hypermobility in 21% of
      school children after a threshold was identified. There was disagreement between
      the scores in school children where 26.7% of children appeared to have a positive
      Beighton score that was not accompanied by a positive lower limb score. In the
      "known hypermobile" group the Beighton score was positive in only 10% of children
      when the lower limb score was negative for hypermobility. CONCLUSION: In this
      group of school children, the Beighton score appeared to over-diagnose
      hypermobility at the threshold of 5/9. Specific thresholds for diagnosis need to
      be set dependant on the age and ethnic group of the population being studied. The
      Lower Limb Assessment Score may be a useful score for health professionals
      specifically interested in lower limb hypermobility.

PMID- 15971436
TI  - Responsiveness of clinical measures to flare of disease activity in juvenile
      idiopathic arthritis.
AB  - OBJECTIVE: To compare the responsiveness of clinical measures in the assessment
      of disease flare in patients with juvenile idiopathic arthritis (JIA). METHODS:
      The clinical records of all consecutive patients with JIA who were diagnosed
      between 1995 and 2000 were retrospectively reviewed. In each patient, all visits
      made during follow-up were analyzed and those meeting the criteria for disease
      flare were recorded. The definition of flare was based on the therapeutic
      alterations made by the attending physician. Responsiveness of JIA clinical
      measures to relevant increase in disease activity (a flare) was evaluated by
      assessing the score change of each measure from a visit made 6 (+/- 3) months
      before a flare and the flare visit. Responsiveness statistics included the
      standardized response mean (SRM) and the effect size (ES). RESULTS: A total of
      115 patients, who were followed for 0.5 to 6.2 years (mean 2.8 years), were
      studied. During follow-up, 51 patients (44%) experienced 1 or more disease
      flares, with the total number of flares being 75. Strong responsiveness (ES and
      SRM > or = 0.8) to increase in disease activity was demonstrated by the
      physician's and parent's global assessments, the global articular severity score,
      and the morning stiffness. The active, swollen and painful joint counts, the
      swelling, pain on motion/tenderness and limited range of motion (LROM) scores,
      and the erythrocyte sedimentation rate revealed moderate responsiveness (ES and
      SRM > or = 0.5). The poorest performances (ES and/or SRM < 0.5) were provided by
      the parent's assessment of pain, the functional ability tool, the number of
      joints with LROM, the LROM score, the C-reactive protein, the white blood cell
      and platelet count, and the hemoglobin level. CONCLUSION: Our analysis suggests
      that the swollen or painful joint counts are better suited than the count of
      joints with LROM for the assessment of disease flare in patients with JIA.

PMID- 15971437
TI  - Myopathy presenting with severe muscle pain.

PMID- 15971438
TI  - The efficacy of a single dose of infliximab in the treatment of Behcet's disease
      uveitis.

PMID- 15971439
TI  - Exuberant macroglossia in a patient with primary systemic amyloidosis.

PMID- 15971440
TI  - Pulmonary granuloma, polyarthritis and antiphospholipids in common variable
      immunodeficiency: resolution after IVIG and the role of immunoglobulin A.

PMID- 15971441
TI  - Development of myositis after hepatitis C virus infection.

PMID- 15971442
TI  - A new case of dermatomyositis following the rupture of a silicone gel breast
      implant.

PMID- 15971444
TI  - Don't be confused--NNOC/CNA is NOT Colorado Nurses Association.

PMID- 15971443
TI  - Coexistence of non-specific and usual interstitial pneumonia in a patient with
      severe cystic scleroderma lung involvement and parvovirus B19 infection.

PMID- 15971445
TI  - Colorado Department of Labor invests in nursing faculty development.

PMID- 15971447
TI  - Pregnancy and breast cancer: epidemiology, treatment, and safety issues.
AB  - The relationship between pregnancy and breast cancer is complex, and a paucity of
      available data further complicates decision-making for many women diagnosed with
      breast cancer during pregnancy or desiring to become pregnant after such a
      diagnosis. Treatment of breast cancer during pregnancy requires a
      multidisciplinary care team and careful consideration of the risk of the disease
      and gestational age of the fetus, in conjunction with the patient's preferences.
      Chemotherapy should be deferred beyond the first trimester. There is no evidence
      that pregnancy in a breast cancer survivor will decrease long-term survival; in
      fact, studies suggest a potential protective effect of pregnancy after breast
      cancer in terms of the risk of recurrence. However, the available studies are
      limited by substantial potential biases, and concerns remain for some women and
      their doctors about the risks of pregnancy after breast cancer. This article
      reviews what is known about the association between pregnancy and breast cancer,
      discusses treatment options for women diagnosed with the disease during
      pregnancy, and summarizes evidence regarding the safety of pregnancy after breast
      cancer.

PMID- 15971448
TI  - Central nervous system germ cell tumors: controversies in diagnosis and
      treatment.
AB  - The variability and complexity of central nervous system germ cell tumors have
      led to controversy in both diagnosis and management. If a germ cell tumor is
      suspected, the measurement of cerebrospinal fluid and serum alpha-fetoprotein and
      beta-human chorionic gonadotropin is essential. A histologic specimen is not
      necessary if the patient has elevated levels; however, if the tumor markers are
      negative, a biopsy is needed to confirm the diagnosis of a germinoma. Germinomas
      are extremely radiosensitive, enabling 5-year survival rates that exceed 90%.
      Treatment has traditionally included focal and craniospinal axis irradiation;
      however, multiple ongoing studies are being conducted to examine the efficacy of
      reduction or elimination of radiation therapy with the addition of chemotherapy.
      Nongerminomatous germ cell tumors, on the other hand, are relatively
      radioresistant with a poorer outcome. The combination of chemotherapy and
      irradiation is associated with overall survival rates of up to 60%. This article
      provides a review of the controversies in diagnosis and treatment of central
      nervous system germ cell tumors.

PMID- 15971449
TI  - Clinical trials referral resource.

PMID- 15971450
TI  - The role of statins in cancer prevention and treatment.
AB  - Statins inhibit the activity of the rate-limiting enzyme in the cholesterol
      biosynthetic pathway, HMG-CoA reductase, and are widely prescribed for lowering
      plasma lipid levels. Several statins have antitumor effects in experimental
      models, and observational studies suggest that this anticancer activity in the
      laboratory may translate into effective treatments and/or preventive strategies
      for certain human cancers. This paper reviews the laboratory and clinical
      evidence that statins have anticancer activity, discusses the possible mechanisms
      by which tumor growth may be inhibited by this class of drugs, and outlines
      strategies for the evaluation of these agents in the prevention and treatment of
      human cancers.

PMID- 15971451
TI  - Revisiting induction chemotherapy for head and neck cancer.
AB  - Squamous cell carcinomas of the head and neck are highly responsive to induction
      chemotherapy. However, randomized trials have failed to demonstrate a survival
      advantage with the addition of induction chemotherapy to locoregional therapy
      consisting of surgery and/or radiation therapy. Currently, concomitant radiation
      and chemotherapy has emerged as a standard and has optimized locoregional control
      in head and neck cancer. In this setting, the addition of induction chemotherapy
      may further improve outcome by enhancing both locoregional and distant control.
      As interest in induction regimens is renewed, we elected to conduct a systematic
      review of trials of induction chemotherapy for locoregionally advanced head and
      neck cancer. The most studied combination--cisplatin plus fluorouracil (5-FU)-
      achieves objective response rates of about 80%. In a meta-analysis, induction
      with platinum/5-FU resulted in a small survival advantage over locoregional
      therapy alone. The introduction of a taxane into induction chemotherapy regimens
      has produced promising results. Induction chemotherapy should be the subject of
      further clinical research in head and neck cancer. Randomized clinical trials in
      which the control arm is concurrent chemoradiotherapy and the experimental arm is
      induction chemotherapy followed by concurrent chemoradiotherapy are planned.
      Platinum/taxane combinations are the preferred regimens for further study in the
      induction setting and a suitable platform with which to investigate the addition
      of novel targeted agents.

PMID- 15971452
TI  - Triple-modality therapy for a woman with locally advanced thoracic esophageal
      adenocarcinoma, part 1.

PMID- 15971453
TI  - Cardiovascular risk profiles around the world.
AB  - In summary, the world is in trouble, but simple lifestyle modifications and drugs
      available to modify risk can change the picture dramatically. Unfortunately, if
      obesity persists, as it seems to be doing in our young people, there may come a
      time when our children's children and their children die at an earlier age than
      their parents.

PMID- 15971454
TI  - Rationale for the use of angiotensin II receptor blockers in patients with left
      ventricular dysfunction (part I of II).
AB  - Almost 5 million individuals in the United States are diagnosed with chronic
      heart failure (HF), and the prevalence is increasing. Angiotensin-converting
      enzyme (ACE) inhibitors and beta blockers, neurohormonal antagonists that block
      the renin-angiotensin system (RAS) and the sympathetic nervous system,
      respectively, have been shown in clinical trials to reduce morbidity and
      mortality in patients with HF, and these therapies are now integral components of
      standard HF treatment. Yet, morbidity and mortality rates in HF remain
      unacceptably high, and the limitations of current standard therapies are becoming
      increasingly apparent. About 10% of patients with HF are unable to tolerate ACE
      inhibitors, often because of cough. In addition, ACE inhibition may not
      completely block the RAS because angiotensin II, the main end product of the RAS,
      can be generated via non-ACE enzymatic pathways. Angiotensin II receptor blockers
      (ARBs) may exert more complete RAS blockade than ACE inhibitors by interfering
      with the binding of angiotensin II at the receptor level, regardless of the
      enzymatic pathway of production. They are also better tolerated than ACE
      inhibitors and have been shown to improve symptoms and function in clinical
      trials in patients with HF. These factors provide a strong rationale for the
      study of the clinical effects of ARBs in patients with HF.

PMID- 15971455
TI  - Thoughts about the ventricular gradient and its current clinical use (part II of
      II).
AB  - The concept of the ventricular gradient was conceived in the mind of Frank Wilson
      in the early 1930s. Wilson, a mathematical genius, believed that the calculation
      of the ventricular gradient yielded information that was not otherwise
      obtainable. The method of analysis was not utilized by clinicians at large
      because the concept was not easy to understand and because the method used to
      compute the direction of the ventricular gradient was so time consuming that
      clinicians could not use it. Grant utilized the concept to create vector
      electrocardiography, but he believed that if his method of analysis was used, it
      was not often necessary to compute the direction of the ventricular gradient. He
      did, however, describe an easy way to compute the direction of the ventricular
      gradient. The current major clinical use of the ventricular gradient is to
      identify primary and secondary T-wave abnormalities in an electrocardiogram
      showing left or right ventricular hypertrophy or left or right ventricular
      conduction abnormalities. In addition, the author uses the term ventricular time
      gradient instead of ventricular gradient in an effort to clarify the concept.
      Finally, the author discusses the possible clinical significance of a normally
      directed, but shorter than normal, ventricular time gradient, an attribute that
      has not been emphasized previously.

PMID- 15971456
TI  - A slight increase of fasting plasma glucose after 2 years was associated with
      electrocardiogram changes suggestive of coronary heart disease in normal
      subjects.
AB  - BACKGROUND: Much attention has been focused on the primary prevention of ischemic
      heart disease (IHD), but the prevalence and prognostic indicators of IHD remain
      unclear in healthy Japanese subjects. HYPOTHESIS: The purpose of this study was
      to determine the predictors for the transition of IHD in healthy adult subjects
      using data from annual medical examinations. METHODS: We analyzed clinical data
      on 2710 healthy subjects (1836 men and 874 women aged 26-76 years in 2000) who
      underwent medical examinations in both 2000 and 2002. Ischemic changes in the
      electrocardiogram (ECG) suggestive of IHD were defined as the existence of
      abnormal Q-wave and/or ST-T abnormalities without left ventricular high voltage.
      We assigned the subjects to two groups: the ischemic heart group (Group I),
      including subjects with normal ECG findings in 2000, followed by suspicious
      ischemic changes in the ECGs in 2002; and the normal group (Group N), including
      subjects with normal ECGs in both 2000 and 2002. RESULTS: Fifty-nine subjects
      (2%, 20 women) were assigned to Group I and 2,538 subjects (96%, 810 women) were
      assigned to Group N. There were significant differences between the two groups in
      baseline age (Group I vs. Group N: 53 vs. 47 years, p < 0.001), body mass index
      (24 vs. 23 kg/m2, p = 0.036), systolic blood pressure (132 vs. 122 mmHg, p <
      0.001), diastolic blood pressure (83 vs. 76 mmHg, p < 0.001), and fasting plasma
      glucose (109 vs. 96 mg/dl, p < 0.001). Fasting plasma glucose significantly
      increased in Group I (from 109 to 113 mg/dl, p = 0.034) during the study.
      Multivariate analysis showed significant differences in age (p < 0.001) and
      fasting plasma glucose (p = 0.0053). CONCLUSION: Advanced age and relatively
      elevated fasting plasma glucose appeared to be significant predictors of ECG
      findings suggestive of IHD in normal subjects in the short period of 2 years.

PMID- 15971457
TI  - Concomitant peripheral vascular and coronary artery disease: a new dimension for
      the global endovascular specialist?
AB  - BACKGROUND: Early and accurate diagnosis of peripheral atherosclerosis is of
      paramount importance for global ma agement of patients with known coronary artery
      disease (CAD). HYPOTHESIS: We sought to evaluate retrospectively the prevalence
      and clinical relevance of significant abdominal vessel stenosis or aneurysm (AVA)
      in patients undergoing coronary angiography. METHODS: Medical records of
      consecutive patients who underwent coronary angiography at two public
      institutions over a 12-month period were evaluated. Angiographic results of
      patients who underwent diagnostic abdominal aorta angiography, based on clinical
      criteria, to evaluate abdominal vessels the same time as coronary angiography
      were analyzed. RESULTS: During the study period, AVA was reported in 180 (35.7%)
      of 504 consecutive patients (335 men, mean age 68 +/- 13.8 years): renal artery
      stenosis was found in 13.1% of cases (66 patients), aortoiliac artery disease in
      13.7% (69 patients and aortic aneurysmal disease in 8.9% (45 patients). Logistic
      regression analyses revealed > or = 3-vessel CAD (odds ratio [OR] 9.917, p =
      0.002), age >65 years (OR 3.817, p = 0.036), > or =3 risk factors (OR 2.8, p =
      0.048) as independent predictors of AVA. CONCLUSION: Multiple vascular
      atherosclerotic distributions are frequent in elderly patients who have
      multivessel CAD and a high-risk profile, suggesting the usefulness of a more
      global and comprehensive cardiovascular approach.

PMID- 15971458
TI  - Coronary artery aneurysms by noncontrast electron beam tomography.

PMID- 15971459
TI  - Peripheral arterial disease, acute coronary syndromes, and early invasive
      management: the TACTICS TIMI 18 trial.
AB  - BACKGROUND: Patients with peripheral arterial disease (PAD) represent a high-risk
      patient subset in the setting of non-ST-segment elevation acute coronary
      syndromes (NSTE ACS). The efficacy and safety of early invasive management for
      such patients remains unclear. HYPOTHESIS: Early invasive management would be
      well tolerated and effective among patients with NSTE ACS and PAD. METHODS:
      Patients from the Treat angina with Aggrastat and determine Cost of Therapy with
      an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction
      (TACTICS-TIMI) 18 trial were stratified by the presence or absence of PAD and
      assessed with respect to baseline clinical factors. The outcomes of patients with
      PAD and NSTE ACS were examined with respect to treatment assignment to either
      early invasive therapy or conservative treatment of NSTE ACS. Finally, the
      bleeding and stroke rates of patients with PAD managed invasively were compared
      with patients with PAD managed conservatively. RESULTS: Of 2219 patients with
      NSTE ACS overall, 166 (7.5%) had concomitant PAD. Compared with those patients
      without PAD, those with PAD were older (75 vs. 62 years, p < 0.001) and were more
      likely to have high-risk clinical features, including prior histories of bypass
      surgery (39 vs. 20%, p < 0.001) or diabetes mellitus (38 vs. 27%, p = 0.002), and
      more ST-segment depression on their 12-lead electrocardiogram (43 vs. 29%, p <
      0.001). Among such patients, early invasive management was associated with
      significant reductions in the risk of myocardial infarction (MI) at 30 days (11.4
      vs. 2.3%, p = 0.03). At 180 days, compared with early conservative management,
      early invasive treatment for patients with PAD and NSTE ACS was associated with
      similar reductions in MI (12.7 vs. 3.5%, p = 0.04), and was also accompanied by
      significant reductions in risk of death (10.1 vs. 2.3%, p = 0.05). No excess in
      bleeding or stroke rates was noted among patients with PAD managed invasively.
      CONCLUSIONS: Among patients with NSTE ACS and a history of PAD, early invasive
      management is well tolerated and accompanied by significant reductions in
      morbidity and mortality when compared with a more conservative, ischemia-driven
      approach.

PMID- 15971460
TI  - The effects of prior beta-blocker therapy on serum C-reactive protein levels
      after percutaneous coronary intervention.
AB  - BACKGROUND: There are no studies in the literature related to the effect of beta
      blockers (BB) on changes in C-reactive protein (CRP) levels after percutaneous
      coronary intervention (PCI). HYPOTHESIS: We designed a prospective randomized
      study to investigate the impact of BB therapy on CRP in patients who underwent
      elective PCI. METHODS: In all, 300 patients with coronary artery disease were
      included. Patients were randomized to either a metoprolol or to a control group
      before PCI. Blood samples for CRP levels were obtained before BB treatment, and
      at the 6th, 24th, and 36th h after PCI. RESULTS: Of 300 patients, 150 received
      metoprolol 100 mg/day (mean age, 59.0 +/- 10.2 years; 106 men, 44 women), and 150
      received no BB (mean age, 59.8 +/- 9.8 years; 114 men, 36 women) and served as
      the control group. Baseline clinical characteristics of both groups were similar.
      Basal CRP levels between the two groups were similar. Of the patients included in
      the study, 40.8% in the BB group and 39.6% in the control group had elevated
      basal CRP levels. The CRP levels increased above baseline values in 85% of
      patients in the BB group and in 89.3% of patients in the control group (p > 0.05)
      during follow-up. The CRP levels in patients in the BB group at the 6th, 24th,
      and 36th h were lower than those in the control group; however, this difference
      did not reach statistical significance. CONCLUSIONS: Prior BB therapy seems to
      have no effect on CRP levels after PCI.

PMID- 15971461
TI  - Comparison of high-density and low-density lipoprotein cholesterol subclasses and
      sizes in Asian Indian women with Caucasian women from the Framingham Offspring
      Study.
AB  - BACKGROUND: Asian Indian women have a higher rate of coronary artery disease
      (CAD) than do other ethnic groups, despite similar conventional risk factors and
      lipid profiles. Smaller high-density lipoprotein cholesterol (HDL-C) particle
      size is associated with reduced cardiac protection or even an increased risk of
      CAD. Exceptional longevity correlates better with larger HDL-C particle sizes.
      HYPOTHESIS: Higher rates of CAD among Asian Indian women may partly be explained
      by the differenes in the prevalence of atherogenic HDL-C and low-density
      lipoprotein cholesterol (LDL-C) sizes and their subclass concentrations among
      Asian Indian women compared with Caucasian women. METHODS: We measured HDL-C
      concentrations and sizes by nuclear magnetic resonance spectroscopy in 119
      relatively healthy Asian Indian women and compared them with those of 1752
      Caucasian women from the Framingham Offspring Study (FOS). RESULTS: Asian Indian
      women were significantly younger (47.9 +/- 11.2 vs. 51.0 +/- 10.1 years, p =
      0.0001), leaner (body mass index 24.0 +/- 4.7 vs. 26.0 +/- 5.6, p = < 0.0002),
      less likely to be postmenopausal (32 vs. 54%, p = < 0.0001), or smoke (< 1 vs.
      20%, p = < 0.0001); nevertheless, prevalence of CAD was higher in Asian Indian
      women (4.2 vs. 1%, p = 0.0006). Asian Indian women had similar HDL-C (53 +/- 13
      vs. 53 +/- 13 mg/dl, p = 0.99), smaller HDL-C particle size (8.9 +/- 0.35 vs. 9.4
      +/- 0.44 nm, p = < 0.0001), higher total cholesterol (209 +/- 40 vs. 199 +/- 42
      mg/dl, p = 0.01), and similar triglyceride (120 +/- 77 vs. 108 +/- 110 mg/d, p =
      0.24) levels. Low-density lipoprotein cholesterol, particle concentrations and
      sizes, as well as prevalence of pattern B were similar. CONCLUSIONS: Compared
      with the FOS, Asian Indian women have significantly smaller overall HDL particle
      size and similar levels of HDL-C, which may reflect impaired, reverse cholesterol
      transport. Total cholesterol was higher, whereas triglyceride and LDL-C levels
      were similar. This may partly explain the higher CAD rates in Asian Indian women.
      Further large scale, prospective, long-term studies are warranted.

PMID- 15971462
TI  - Johann Nepomuk Czermak and his isolated frog heart.

PMID- 15971463
TI  - Current epidemiology of asthma: emerging patterns of asthma.
AB  - Asthma is a chronic disease associated with substantial morbidity, mortality, and
      health care use. Between 1980 and 1994, the self-reported prevalence of asthma
      increased 75% among all race, sex, and age groups in every region of the United
      States. Although an estimated 14.6 million persons had asthma in the United
      States in 1996, more recent studies have suggested a plateauing of the prevalence
      of the disease. Because establishing the diagnosis of asthma and characterizing
      the features of the disease have long been difficult for both the clinician and
      the researcher, studies determining the frequency of asthma across different
      countries and over time, seeking clues to the etiology of the disease, and
      monitoring for untoward variations provide the clinician with additional
      resources to manage patients with asthma. The purpose of this article is to
      provide a brief overview of the current and emerging national and international
      trends in the epidemiology of asthma.

PMID- 15971464
TI  - Asthma concepts in the new millennium: update in asthma pathophysiology.
AB  - This article reviewed current concepts of airway inflammation with a special
      emphasis on the epithelium, smooth muscle dysfunction, and airway remodeling. An
      alternative therapy on the importance of the airway microenvironment or
      epithelial mesenchymal trophic unit, myofibroblast activation, and role of growth
      factors was addressed. Future therapeutic strategies may involve these targets
      and a synergistic approach in preventing remodeling in selected asthmatic
      patients.

PMID- 15971465
TI  - What is the best marker for inhaled corticosteroid safety?
AB  - The development of modern corticosteroids has revolutionized the treatment and
      management of asthma. Importantly, to a great extent, it has reduced the
      incidence of systemic side effects. However, at high doses, inhaled
      corticosteroid therapy is not devoid of systemic side effects such as growth
      suppression, reduction in bone density, and cataracts. Hence, it becomes
      important to monitor these effects. The most commonly used parameters that are
      monitored for systemic steroid effects measure the endogenous cortisol secretion.
      Measured parameters allow a direct comparison of the degree of systemic activity,
      which is difficult, based on steroid drug levels, because of the difference in
      potency of the various compounds. Evaluation of endogenous cortisol
      concentrations is complicated because of the presence of a circadian rhythm with
      highest cortisol concentrations in the morning and trough concentrations around
      bedtime. However, methods are available that consider circadian cortisol
      secretion. Cortisol levels should be measured over 24 hours at steady state. The
      area between the serum cortisol concentrations in the control group and the
      suppressed group is recognized as a good cumulative marker of systemic steroid
      activity. Cortisol suppression is a more sensitive marker for inhaled
      corticosteroid safety than parameters that consider effects on bone or lymphocyte
      suppression. If an inhaled corticosteroid dosing regimen does not show any
      significant cortisol suppression based on 24-hour serum area under the curve
      values, it can be assumed that this treatment is safe and unlikely to present any
      clinically relevant safety with respect to systemic steroid activity.

PMID- 15971466
TI  - Antihistamines: treatment selection criteria for pediatric seasonal allergic
      rhinitis.
AB  - Given the absolute numbers of children suffering from seasonal allergic rhinitis
      (SAR) and the fact that this number is rising, there is an unquestionable need
      for safe and effective treatments for the disease. The limited seriousness of the
      symptoms of SAR belies their true impact: the disease can have a profound effect
      on children's quality of life and impair learning performance. Furthermore, SAR
      has been linked to a number of comorbid conditions and forms part of the
      "allergic march" to more serious diseases such as asthma. Antihistamines are
      administered to relieve the symptoms of SAR, but they do not represent a
      homogeneous group. For example, older-generation antihistamines are associated
      with side effects such as impaired psychomotor performance. Newer-generation
      antihistamines must be evaluated individually based on their proven efficacy and
      safety so as to tailor treatment to each child's needs. Effective and safe
      treatment of SAR, with an antihistamine that does not cause sedation, should
      improve children's quality of life and could prevent the development of more
      serious conditions, thus reducing morbidity and possible future health care
      expenditure.

PMID- 15971467
TI  - Ragweed skin test responsiveness correlates with specific immunoglobulin E
      levels.
AB  - Evaluation for allergic rhinitis requires an objective measure of atopy. Serum
      eosinophils, total and specific immunoglobulin E (IgE), and skin testing have
      been used as this measure. The objective of our study was to examine the
      relationship between in vitro allergy tests and in vivo responsiveness. We
      compared eosinophil counts, total IgE, and the specific IgE radioallergosorbent
      test (RAST) measurements to end point skin test titrations with ragweed. Forty
      subjects > or = 18 years of age with at least a 2-year history of moderate to
      severe ragweed-allergic rhinitis and a positive skin-prick test to ragweed
      participated in this study with 33 subjects having data for all measurements. End
      point skin tests were performed by intradermal injection of 0.03 mL of threefold
      dilutions of standardized short ragweed extract into the forearm. Ragweed
      specific IgE was significantly correlated to end point wheal and erythema
      concentrations. The results were similar whether the endpoint wheal (r = -0.714;
      p < 0.001) or erythema (r = 0.862; p < 0.001) concentration was used, and the
      correlation between these two values was significant (r = 0.97; p < 0.001).
      However, 8 of 33 subjects had a negative specific IgE RAST value for ragweed.
      There was a significant relationship between ragweed-specific IgE and total IgE
      (r = 0.72; p < 0.01). No significant correlations were found between blood
      eosinophils and either total IgE, ragweed-specific IgE, and end point wheal or
      erythema concentrations. Skin test responsiveness to ragweed correlated with in
      vitro ragweed-specific IgE levels, but these tests are not equivalent indicators
      of the degree of IgE-mediated sensitivity.

PMID- 15971468
TI  - Aeroallergen hypersensitivity: comparing patients with nasal polyps to those with
      allergic rhinitis.
AB  - Immunoglobulin E-mediated allergy generally has not been considered to be
      important in the pathogenesis of nasal polyps, despite elevated immunoglobulin E
      in polyp exudates, tissue eosinophilia, and degranulated mast cells. In previous
      reports, patients with nasal polyps were more likely to have positive skin tests
      to perennial than to seasonal allergens. It is postulated that nasal polyps
      result from the constant nature of perennial allergen exposure. The objective of
      this report is to compare the prevalence of sensitization to six aeroallergens in
      a group of nasal polyp (NP) patients, a group of allergic rhinitis (AR) patients,
      and those subjects with positive skin tests in the National Health and Nutrition
      Examination Survey (NHANES) II. Twenty-five consecutive NP patients evaluated
      over a 3-month period of time at Northwestern Allergy and Immunology Outpatient
      Center, in addition to 50 of the allergic rhinitis patients evaluated over the
      same time, were chosen randomly. All were skin tested with the following
      antigens: dog, cat, dust mite, grass, tree, and ragweed. Published skin test data
      from the NHANES II study of 14,367 individuals was obtained also. The percent of
      NP patients, AR patients, and NHANES II subjects with sensitization to perennial
      allergens was 72, 96, and 7.6%, respectively. The difference between the AR and
      NP patients was statistically significant (p = 0.006). The percent of NP, AR, and
      NHANES II subjects sensitized to seasonal allergens was 84, 86, and 17.7%,
      respectively. No statistical significance existed between the AR and NP patients,
      regarding seasonal allergens. Although the AR and NP had similar levels of
      reactivity to perennial and seasonal allergens, the NHANES II group was more than
      twice as likely to be sensitized to a seasonal allergen. The NP and AR groups
      were similar in prevalence of reactivity to seasonal allergens, but the NP
      patients in our population actually were less likely to be sensitized to
      perennial allergens than individuals with AR.

PMID- 15971469
TI  - Poplar pollen-related allergy in Ankara, Turkey: how important for patients
      living in a city with high pollen load?
AB  - The impact of high pollen load of particular plants on sensitized subjects is a
      topic of interest. We aimed to detect the clinical importance of poplar allergy
      in subjects with seasonal allergy living in Ankara, capital city of Turkey,
      having a high poplar pollen load. The subjects with seasonal allergy and
      demonstrating allergy to Populus alba in skin-prick tests (SPTs) (n = 20)
      underwent a specific nasal provocation test with P. alba allergen extract and
      were requested to fill in symptom-medication reports. During the same period, P.
      alba and Gramineae pollen counts were assessed in the city. Pollination for P.
      alba in Ankara for the year 2001 started in the 2nd week of March and terminated
      in the 1st week of May; 96.5% of subjects also had grass pollen sensitivities. By
      history, 85% of the subjects described mild symptoms in March and April, the
      expected pollinosis season for P. alba. Symptom and medication scores were higher
      in May and June than in March and April (p < 0.05). Allergy to P. alba pollen in
      patients with seasonal allergy causes mild symptoms where the dominant clinical
      presentation was demonstrated to be due to their additional Gramineae (grass)
      pollen allergy.

PMID- 15971470
TI  - Atopic status in patients with sarcoidosis.
AB  - Sarcoidosis is a multisystem disorder that is characterized by T helper 1 (Th1)
      mediated immune response at the sites of disease. Studies showed that T cells
      derived from patients with sarcoidosis have been able to release Th2 cytokine
      profile. However, they are believed to be suppressed and nonactive. This study
      investigated the rate of atopy, a Th2 condition, in sarcoidosis. Atopic status
      was assessed in 41 patients (13 men and 28 women; mean age, 47.6 +/- 12.2 years)
      with sarcoidosis. Current history of atopic diseases, including asthma and
      allergic rhinitis, was assessed in clinical evaluation. Skin-prick tests were
      performed using a standardized panel. Total immunoglobulin E was measured by
      chemiluminescence automatic immunoassay. Results are discussed with the
      conjunction of previous epidemiological studies conducted in adult Turkish
      populations. Three patients (7%) had a diagnosis of asthma, whereas one patient
      (2%) had isolated allergic rhinitis. Skin-prick tests were positive in two
      patients (5%). This rate is much lower than the atopy prevalence in Turkey (5%
      versus 25%). Our data suggest that sarcoidosis may be associated with a lower
      incidence of atopy and allergic disease; further data are needed in other
      populations.

PMID- 15971471
TI  - Cerebrospinal fluid leak mimicking allergic rhinitis.
AB  - Rhinitis and rhinorrhea are common clinical complaints that may be allergic or
      nonallergic in etiology. Distinguishing between allergic and nonallergic
      etiologies can be difficult but necessary for treatment. Here, we present a case
      of a 50-year-old woman with > 20 years of rhinorrhea before a diagnosis of
      cerebrospinal fluid leak and a life-threatening complication occurred. It is
      essential that no symptom, especially that which persists and resists treatment,
      is trivialized. Here, we establish how a careful history and evaluation will
      direct the clinician to the correct diagnosis.

PMID- 15971472
TI  - Maintenance asthma treatment with fluticasone/salmeterol combination via Diskus:
      effect on outcomes in inner-city children enrolled in TennCare.
AB  - Although current national guidelines suggest combination inhaled
      corticosteroid/long-acting inhaled beta2-agonist as the preferred treatment in
      moderate and severe persistent asthma for children, trials aimed at reducing
      emergency department (ED) visits and hospitalizations in minority inner-city
      children have not been conducted with the combination product of
      fluticasone/salmeterol via Diskus (Advair). This study assessed the effect of
      fluticasone/salmeterol combination via Diskus therapy on hospitalizations and ED
      visits in children with asthma. We conducted a prospective 1-year study with an
      intervention group compared with a usual care control group. This study took
      place at an inner-city university-affiliated children's medical center allergy
      clinic. Inner-city patients with asthma aged 4-17 years with a history of
      frequent ED visits and hospitalizations for the 2 previous years were enrolled
      beginning in July 2001. A control group of inner-city asthmatic patients was
      identified via hospital medical records. Patients were prescribed
      fluticasone/salmeterol combination via Diskus (n = 39) for 1 year and were
      compared with a usual care control group (n = 39). Although the investigators did
      not intervene in the control patients, review of their records revealed that all
      control patients had inhaled corticosteroids prescribed during the intervention
      period. Outcome measures included ED visits and hospitalizations for 1 year after
      enrollment versus the mean for acute care visits for 2 years before enrollment in
      the study. The intervention group had a 20% reduction in ED visits, which was
      significant compared with the control group (p = 0.017); both groups had
      significant reductions in hospitalizations. The risk of experiencing an asthma
      exacerbation (ED visit or hospitalization) was reduced by 33% in the intervention
      group compared with the control group (risk ratio, 0.67; 95% confidence interval,
      0.49-0.90; p = 0.005). Our results suggest that fluticasone/salmeterol
      combination via Diskus is associated with a reduction in risk of acute
      exacerbations of asthma in inner-city children, including ED visits and
      hospitalizations.

PMID- 15971473
TI  - Adverse drug reactions to a cephalosporins in hospitalized patients with a
      history of penicillin allergy.
AB  - Estimates on the cross-reactivity between cephalosporin and penicillin range from
      1 to 16%. Patients with a history of penicillin allergy usually receive less
      optimal and more costly alternatives even if cephalosporins are a more viable
      alternative. One hundred eighty-six patients admitted to Winthrop University
      Hospital in a 7.5-month period, who reported penicillin allergy and received
      cephalosporin, were sent surveys. Eighty-three patients completed the survey and
      their charts were reviewed. Seven of 83 patients (8.4%) from a larger group of
      186 penicillin-allergic patients developed a reaction to a cephalosporin. The
      exact 95% confidence interval is 3.5-16.6%. Six of seven (85.7%) penicillin
      allergic patients who reacted to cephalosporin reported a definite history of an
      immediate reaction to penicillin, including hives. Only 1 of 62 (1.6%) patients
      who reported that their penicillin reaction was delayed, probable, or unknown had
      a cephalosporin reaction (p < 0.001). Thirty percent (3 of 10 patients) of
      penicillin-allergic patients, who received a second-generation cephalosporin, had
      a reaction, whereas 5.5% (4 of 73 patients) of those patients given only a first
      , third-, and fourth-generation cephalosporin reacted (p < 0.04). None of those
      patients who received a fourth-generation cephalosporin reacted. Four of 15
      (26.7%) patients who received a cephalosporin with an amino benzyl ring developed
      a reaction, as compared with 3 of 68 (4.4%) patients who received a cephalosporin
      without the ring (p < 0.02). Four patients with severe cephalosporin reactions
      had a rash, shortness of breath, difficulty swallowing, lightheadedness, and
      anaphylaxis. Patients who recall a definite history of an immediate type of
      penicillin allergy are more likely to develop a cephalosporin reaction compared
      with patients who reported a delayed, a probable, or an unknown penicillin
      reaction. Penicillin-allergic patients who receive second-generation
      cephalosporins, especially those with an amino benzyl side chain, are more likely
      to develop a reaction to cephalosporin. Although the incidence of reactions to
      cephalosporin in penicillin-allergic patients is low, those patients who reacted
      had more severe manifestations including anaphylaxis. Thus, continued caution
      regarding administration of cephalosporin, especially those with amino benzyl
      side chains, to patients who have a definite history of an immediate reaction to
      penicillin is advised.

PMID- 15971474
TI  - Clinical pearls and pitfalls: peanut allergy.
AB  - A case of pediatric peanut allergy is presented. Pathophysiology, clinical
      characteristics, diagnostic test, case management, and natural history are
      reviewed. Clinical Pearls and Pitfalls include: (1) About 20% of young infants
      will outgrow peanut allergy, especially if IgE levels measured by ImmunoCAP RAST
      are less than SkU/L. (2) Cases of resensitization have been documented after
      negative peanut oral challenges. (3) Only a negative food challenge can provide
      convincing evidence that the patient has outgrown his or her peanut allergy.

PMID- 15971475
TI  - Joint Council of Allergy, Asthma, and Immunology news: focus on coding.

PMID- 15971476
TI  - Reproductive outcome after strassman metroplasty in women with a bicornuate
      uterus.
AB  - OBJECTIVE: To describe the reproductive outcome in 22 women with a bicornuate
      uterus who underwent Strassman metroplasty. STUDY DESIGN: The study analyzed
      pregnancy outcomes. RESULTS: Of women who had undergone Strassman metroplasty,
      88% achieved pregnancies that ended with the birth of a viable infant. A total of
      19 infants were born. All pregnancies that ended at term had normal courses, and
      a cesarean section was performed in all cases. The "take-home-baby" rate was 100%
      for the first postoperative pregnancy. CONCLUSION: The postmetroplasty
      reproductive capacity of women with a bicornuate uterus was very good. Strassman
      metroplasty should be reserved for selected women with bicornuate uteri who have
      experienced recurrent spontaneous abortion or preterm birth.

PMID- 15971477
TI  - Umbilical cord prolapse in current obstetric practice.
AB  - OBJECTIVE: To assess the incidence, risk factors and outcomes of umbilical cord
      prolapse in current obstetric practice. STUDY DESIGN: This study was a
      retrospective chart review at both a community hospital and a tertiary referral
      center. RESULTS: There were 52 cases of cord prolapse in our patient population,
      for an incidence of 3.0/1,000, similar to that in the literature. Of viable
      singleton pregnancies with frank prolapse, the rate was 1.6/1,000. In this series
      we found an approximately 40% higher rate of frank cord prolapse in induced
      patients at the community hospital than in the general population. Other than 2
      fetal deaths related to extreme prematurity, all mothers and infants did well.
      CONCLUSION: The higher incidence of cord prolapse among women with induction of
      labor in this population merits further study. The lack of significant morbidity
      and mortality in the study suggests that modern obstetric practices may
      influenced the natural history of umbilical cord prolapse.

PMID- 15971478
TI  - Genetic origin and imprinting in hydatidiform moles. Comparison between DNA
      polymorphism analysis and immunoreactivity of p57KIP2.
AB  - OBJECTIVE: To evaluate whether p57KIP2 expression is concordant with the result
      of DNA polymorphism analysis in molar pregnancy. STUDY DESIGN: Eleven molar
      pregnancies diagnosed by pathologic findings between October 2002 and April 2004
      were studied. Histopathologic diagnosis, DNA polymorphism analysis and p57KIP2
      immunohistochemistry were investigated. RESULTS: DNA polymorphism analysis
      identified 3 biparental conceptuses as well as 4 dispermic androgenetic complete
      moles (CMs) and 4 suggestive monospermic CMs. Distinctly positive nuclear
      immunoreactivity of p57KIP2 was observed in a significant proportion of the
      villous cytotrophoblast and mesenchyme (30-60% of cells positive) in 3 cases of
      biparental conceptuses proven by DNA polymorphism. In contrast, p57KIP2
      expression was negative (< 5% positive cells) in either the villous
      cytotrophoblast or mesenchyme in 8 cases of androgenetic conceptuses proven by
      DNA polymorphism. In all 11, p57KIP2 immunostaining was observed in the nuclei of
      extravillous trophoblasts that served as internal positive controls. CONCLUSION:
      Negative p57KIP2 immunoreactivity (paternally imprinted, maternally expressed
      gene) was in perfect concordance with the androgenetic origin of molar
      pregnancies proven by DNA polymorphism. The results suggest that p57KIP2
      immunoreactivity, which can be performed in routine pathologic examinations, is a
      promising ancillary diagnostic tool to differentiate androgenetic CM from
      biparental conceptuses.

PMID- 15971479
TI  - Bacterial vaginosis and preterm delivery: an open question.
AB  - OBJECTIVE: To evaluate the prevalence of bacterial vaginosis in a population of
      Italian pregnant women and to study its association with adverse pregnancy
      outcomes, particularly preterm delivery. STUDY DESIGN: After giving informed
      consent, 598 women were consecutively enrolled at their first prenatal visit (13
      18 weeks of gestation). The presence of bacterial vaginosis was assessed by
      Gram's method at 13-18 weeks of gestation (early bacterial vaginosis) and at 28
      32 weeks of gestation (late bacterial vaginosis). Univariate and multiple
      logistic regression models of analysis were used to assess the statistical
      significance of the data. RESULTS: Preterm delivery occurred in 14.7% of pregnant
      women positivefor bacterial vaginosis at theirfirst prenatal visit and in 6.9% of
      healthy women (OR 1.6, CI 1.07-2.51). In patients with bacterial vaginosis,
      preterm delivery occurred more often in the 36th week of gestation (78.6%).
      CONCLUSION: The presence of bacterial vaginosis at an early gestational age is
      associated with preterm delivery, although in the study population the condition
      did not seem to be related to great prematurity.

PMID- 15971480
TI  - Advanced maternal age and fetal growth inhibition in triplets.
AB  - OBJECTIVE: To determine whether advanced maternal age is associated withfetal
      growth inhibition in triplets. STUDY DESIGN: We conducted a retrospective cohort
      study on triplet live births in the United States from 1995 through 1998. The
      outcomes of fetal growth inhibition measured were low birth weight, very low
      birth weight, preterm birth, very preterm birth and smallnessfor gestational age.
      We generated adjusted ORs after taking into account intracluster correlations
      using the generalized estimating equation framework. RESULTS: As compared to
      women of younger maternal age (20-29), mature (30-39) and older women (> or =40
      years) with triplet gestations tended to have a lower likelihood offetal growth
      inhibition. Mean birth weight and mean gestational age at delivery increased with
      increasing maternal age in a dose-dependent pattern (p for trend < 0.0001). As
      compared to triplets born to younger mothers, those of older women were less
      likely to have low birth weight (OR=0.51, 95% CI=0.37-0.69) or very low birth
      weight (OR = 0.58, 95% CI = 0.47-0.72) or to be preterm (OR = 0.39, 95% CI = 0.27
      0.56) or very preterm (OR = 0.67, 95% CI = 0.55-0.80). The riskfor small-for
      gestational-age infants was comparable. CONCLUSION: Older maternal age is
      associated with morefavorable triplet fetal growth parameters, although the exact
      mechanisms of this paradox remain poorly understood.

PMID- 15971481
TI  - Serotonergic activity and the Beck Depression Inventory in the premenstrual
      syndrome.
AB  - OBJECTIVE: To investigate the relationship between platelet [3H]-imipramine
      binding and Beck Depression Inventory scores in the premenstrual syndrome (PMS).
      STUDY DESIGN: Thirty-one patients with PMS and 26 healthy female volunteers
      participated in the study. Imipramine binding was measured by saturation binding
      of [3H]-imipramine. The Beck Depression Inventory form was completed. RESULTS:
      The number of [3H]-imipramine binding sites (Bmax) was significantly lower in the
      study group (p = 0.003). Beck Depression Scores were significantly higher in the
      study group as compared with the control group (p = 0.001). No correlation was
      found between platelet [3H]-imipramine binding and Beck Depression Inventory
      scores (r = 0.100, p = 0.591). CONCLUSION: A significantly lower number of Bmax
      wasfound in patients with PMS as compared to controls, but no correlation between
      platelet [3H]-imipramine binding and Beck Depression Inventory scores was found.

PMID- 15971483
TI  - Laser ablation of surgical margins after excisional partial vulvectomy for VIN:
      Effect on recurrence.
AB  - OBJECTIVE: To determine the recurrence rates in patients who underwent different
      surgical treatments for vulvar intraepithelial neoplasia (VIN) 2 and 3. STUDY
      DESIGN: Data on every patient who underwent surgical treatment for VIN 2 or 3
      between January 1994 and December 2002 by a single gynecologic oncologist were
      retrospectively reviewed. The recurrence rates for 3 different surgical therapies
      were analyzed using Fischer's exact test. RESULTS: Thirty-three patients, who had
      a median age of 46 years (range, 31-80), were identified. The preoperative biopsy
      demonstrated VIN 2 or 3 in 9.1% and 90.9% of the patients, respectively. The
      following primary surgical procedures were employed: 16 patients (48.4%)
      underwent excisional partial vulvectomy with CO2 laser ablation of the margins,
      10 patients (30.3%) had CO2 laser ablation alone, 6 patients (18.2%) had an
      excisional partial vulvectomy, and 1 patient (3.0%) was. treated with the
      ultrasonic surgical aspirator. No patient had invasive disease. Recurrent disease
      was seen in 7 patients (70.0%) treated by laser alone, 3 patients (50.0%) who had
      an excisional partial vulvectomy and 1 patient (6.25%) who underwent a combined
      laser and excisional partial vulvectomy (p = 0.0016). CONCLUSION: The results of
      this small study suggest that laser and excisional partial vulvectomy for the
      treatment of VIN 2 and 3 may be associated with a lower recurrence rate than
      either modality alone. A larger study will be needed to confirm these results.

PMID- 15971482
TI  - Dietary fiber, potassium, magnesium and calcium in relation to the risk of
      preeclampsia.
AB  - OBJECTIVE: To explore the relation between preeclampsia risk and maternal intake
      of dietary fiber, potassium, magnesium and calcium. STUDY DESIGN: We conducted a
      case-control study of 172 preeclamptics and 339 normotensive controls. Maternal
      dietary intake was assessed using a food frequency questionnaire. Logistic
      regression procedures were used to estimate the association between each dietary
      factor and preeclampsia risk. RESULTS: Fiber intake was inversely associated with
      the risk of preeclampsia. When extreme quartiles of total fiber intake were
      compared, the odds ratio (OR) for preeclampsia was 0.46 (95% confidence interval
      [CI] 0.23-0.92). The multivariate OR for preeclampsia for women in the top
      quartile of potassium intake (> 4.1 g/d) versus the lowest quartile (< 2.4 g/d)
      was 0.49 (95% CI 0.24-0.99). There was some evidence ofa reduced risk of
      preeclampsia with a high intake of magnesium and calcium, though these results
      were not statistically significant. Intake offruits and vegetables, low-fat dairy
      products, total cereal and dark bread were each associated with a reduced risk of
      preeclampsia. CONCLUSION: Our results support previous reports that suggest that
      diets high in fiber and potassium are associated with a reduced risk of
      hypertension. Maternal intake of recommended amounts of foods rich in fiber,
      potassium and other nutrients may reduce the risk of preeclampsia.

PMID- 15971484
TI  - Correlation of United States medical licensing examination step 2 and obstetrics
      and gynecology clerkship final examination scores with clerkship clinical
      evaluation scores.
AB  - OBJECTIVE: To determine if a student's subjective clinical evaluation score (CES)
      correlates with United States Medical Licensing Examination (USMLE) Step 1 or
      Step 2, obstetrics/gynecology clerkship final examination or Medical College
      Admission Test (MCAT) scores. STUDY DESIGN: The test scores for all students
      rotating at Texas Tech Health Sciences Center at Amarillo from 1994 to 2002 were
      obtained. Regression models were used to compare the CES and examination scores.
      The 10th percentile of the CES was statistically compared with each examination
      score as well as its 10th percentiles. RESULTS: The mean scores for the 285
      students were USMLE Step 1, 204.4; USMLE Step 2, 205.0; MCAT, 29.1;
      obstetrics/gynecology final, 86.0; CES, 88.5. Linear correlations were found
      between the CES and USMLE Step 2 (r = 0.26, p < 0.001) and the
      obstetrics/gynecology final (r=0.25, p<0.001). Students with a poor CES (<10th
      percentile) had lower USMLE Step 2 scores, (188.2 vs. 206.3, p < 0.001) and more
      examination failures (odds ratio [OR] 8.9 [2.3-33.9]) as well as both lower
      obstetrics/gynecology final examination scores (81.1 vs. 86.3, p < 0.001) and
      more clerkship failures (OR 14.2 [1.9-107.4]). CONCLUSION: Students' subjective
      CESs correlate linearly with performance on both the USMLE Step 2 and
      obstetrics/gynecology final examinations. Poor CESs (< 10th percentile) predicted
      lower scores on the future standardized examinations studied.

PMID- 15971485
TI  - Association of leptin with poor ovarian stimulation during in vitro
      fertilization.
AB  - OBJECTIVE: To evaluate whether serum leptin levels are predictive of in
      vitrofertilization (IVF) outcome. STUDY DESIGN: A nested, case-control study was
      performed on patients undergo-formed on patients undergoing IVF. Ovarian
      stimulation was performed with a set protocol. At the conclusion of the
      stimulation, patients were divided into 2 groups, poor stimulator (PS) and high
      stimulator (HS), based on the number of follicles seen on ultrasound. The PS
      group contained patients with < 12 follicles > 13 mm in diameter; the HS group
      contained patients with > or = 12 follicles > 13 mm. Blood from the start of the
      cycle in which human chorionic gonadotropin (hCG) was administered was assayed
      for leptin and estradiol. The number of follicles obtained, number of oocytes
      retrieved, quality of the oocytes and quality of the embryos were calculated.
      Mean leptin and estradiol levels were compared using Student's t test. Pearson
      correlation coefficients were calculated to assess the relationship between
      leptin and the other outcome variables. RESULTS: Mean leptin levels (+/- SEM) at
      the start of the cycle (21.5 +/- 2.9 ng/dL for PS and 34.6 +/- 14.0 ng/dL for HS)
      and on the day of hCG (53.2 +/- 5.37 ng/dL for PS and 50.4 +/- 9.1 ng/dL for HS)
      were not significantly different. CONCLUSION: Leptin levels obtained at the start
      of stimulation or on the day of hCG administration are not predictive of IVF
      outcome.

PMID- 15971486
TI  - Reproduction and ulcerative colitis: a review.
AB  - Ulcerative colitis is a chronic inflammatory bowel disease. The onset peaks at
      age 15-30 years and coincides with the reproductive period. We screened and
      summarized the relevant English-language publications (Entrez-PubMed) on
      ulcerative colitis, fertility and pregnancy. The presence of ulcerative colitis
      per se does not seem to significantly alterfertility in young women. However,
      associated conditions, such as active disease, surgical interventions and
      medication, may interfere with reproduction. It is difficult to draw conclusions
      regarding the effect of ulcerative colitis on pregnancy outcome in terms of
      pregnancy loss, intrauterine growth restriction, low birth weight, preterm labor,
      stillbirth and perinatal mortality. Nevertheless, it appears that major
      complications do not occur in ulcerative colitis patients more frequently than in
      healthy women. The rate of exacerbation is probably the same for pregnant and
      nonpregnant women. Disease control during pregnancy is of the utmost importance.
      Fortunately, most drugs can by used safely during pregnancy.

PMID- 15971487
TI  - Antenatal course of a fetal intracranial arteriovenous fistula: a case report.
AB  - BACKGROUND: Intracranial arteriovenous fistulas (AVFs) are rare in childhood.
      AVFs in fetuses are very rare and usually not associated with the vein of Galen.
      These can be solitary or multiple and may be associated with aneurysms or AVMs.
      The presentation of an AVF depends on the age of the patient, site and size of
      the fistula, and any accompanying lesion. Neonates can present with cardiac
      failure and a cranial bruit, infants with cardiomegaly and cardiac failure,
      children with hydrocephalus, and adolescents and adults with headaches, seizures
      or intracranial hemorrhage. CASE: Ultrasound and Doppler flow studies revealed a
      large, vascular lesion in the left cerebral hemisphere that was consistent with
      an arteriovenous malformation or fistula. The fetus developed cardiomegaly and
      transient pleural effusion not hydrops. Planned cesarean section without
      manipulation of thefetal head was performed at 39 weeks. Embolization during the
      neonatal period completely ceased flow through the arteriovenous fistula. At 28
      months of age the child was doing well and showed no developmental or neurologic
      deficits. CONCLUSION: Prenatal recognition of fistulas and malformations can
      result in a good outcome as long as thefetus does not develop cardiac failure.
      Knowledge of the presence of an extensive arteriovenous malformation orfistula
      prior to birth allows planned delivery and permits the parents and medical team
      to be prepared for treatment at a tertiary care center.

PMID- 15971488
TI  - Autosomal dominant polycystic kidney disease in pregnancy complicated by twin
      gestation and severe preeclampsia: a case report.
AB  - BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD), an autosomal
      dominant genetic disorder with a reported prevalence of 1 in 1,000, may be
      associated with hypertensive disease in pregnancy. The evaluation of a pregnant
      woman with an adult-onset genetic disorder is complex and involves counseling
      about inheritance, prenatal diagnosis and management of the current pregnancy.
      CASE: A 33-year-old woman presented for obstetric care with a history of
      hypertension and ADPKD for 6 years. The patient had secondary infertility, which
      was treated by in vitro fertilization. The case was complicated by twin gestation
      and superimposed severe preeclampsia, leading to preterm cesarean delivery at 26
      weeks' estimated gestational age. CONCLUSION: Because of the heritable nature of
      ADPKD and the long-term risk of end-stage renal disease requiring dialysis and/or
      renal transplantation, the evaluation and counseling of women with ADPKD who are
      pregnant or considering pregnancy should include a discussion of the modes of
      inheritance, natural history, available prenatal diagnostic options, and
      pregnancy risks and management options. Specific counseling issues in this case
      include the genetic concepts of variable expression and penetrance and the
      medical management of chronic hypertension and preeclampsia.

PMID- 15971489
TI  - Successful pregnancy in a Noonan syndrome patient after 3 unsuccessful
      pregnancies from severe fetal hydrops: a case report.
AB  - BACKGROUND: Noonan syndrome is a very rare disorder; its prevalence is 1/1,000
      2,500 births. The special facial features, short stature, eventual cardiac
      anomalies and familiar history are the most important characteristics of the
      diagnosis. CASE: A Noonan syndrome patient delivered a healthy infant after a
      complicated delivery. The delivery followed 3 unsuccessful pregnancies. The
      previous pregnancies were terminated before the 24th gestational week because of
      general fetal hydrops as well as other malformations. CONCLUSION: In the prenatal
      care of a patient with Noonan syndrome the genetic and obstetric aspects are
      equally important. In establishing the diagnosis, ultrasonography is of utmost
      importance. As in our case, complications after cesarean section highlight the
      higher risk of delivery in women with Noonan syndrome.

PMID- 15971490
TI  - Behavioral and associative effects of differential outcomes in discrimination
      learning.
AB  - The role of the reinforcer in instrumental discriminations has often been viewed
      as that of facilitating associative learning between a reinforced response and
      the discriminative stimulus that occasions it. The differential-outcome paradigm
      introduced by Trapold (1970), however, has provided compelling evidence that
      reinforcers are also part of what is learned in discrimination tasks.
      Specifically, when the availability of different reinforcing outcomes is signaled
      by different discriminative stimuli, the conditioned anticipation of those
      outcomes can provide another source of stimulus control over responding. This
      article reviews how such control develops and how it can be revealed, its impact
      on behavior, and different possible mechanisms that could mediate the behavioral
      effects. The main conclusion is that differential-outcome effects are almost
      entirely explicable in terms of the cue properties of outcome expectancies
      namely, that conditioned expectancies acquire discriminative control just like
      any other discriminative or conditional stimulus in instrumental learning.

PMID- 15971491
TI  - Transposition in pigeons: reassessing Spence (1937) with multiple discrimination
      training.
AB  - We studied transposition in pigeons, using multiple-pair discrimination training.
      Four birds discriminated two pairs of circles: 1+ 2- and 5+ 6- or 1 - 2 + and 5-
      6 + (digits denote circle diameters and plus and minus signs denote reward and
      nonreward, respectively). Four other birds discriminated four pairs of circles:
      1+ 2-, 1+ 3-, 4+ 6-, and 5+ 6- or 1- 2 +, 1- 3 +, 4- 6+, and 5- 6+. Finally, 4
      birds discriminated only one pair of circles: 1+ 2-, 1- 2+, 5+ 6-, or 5- 6+.
      Testing included five new pairs--1/5, 2/3,2/6,3/4, and 4/5--that distinguished
      absolute from relational accounts of transposition. The pigeons' relational
      responding rose from one- to two- to four-pair training. The similarity of the
      testing stimuli to one another also affected relational responding: Transposition
      increased with highly dissimilar stimuli. Neither Spence's (1937) theory nor
      existing relational accounts could predict the obtained pattern of relational
      responding.

PMID- 15971492
TI  - Methodological-conceptual problems in the study of chimpanzees' folk physics: how
      studies with adult humans can help.
AB  - In three experiments, we examined humans' folk physics (i.e., a naturally
      occurring and spontaneous understanding of the physical world), using variations
      of problems used to study chimpanzees' folk physics. Presented with trap-tube
      problems in two experiments, adult humans showed an unnecessary bias to insert a
      stick into the end of the tube farthest from the reward to push it out the other
      end. When presented with trap-table problems with ineffective trapping holes,
      people unnecessarily avoided the side with the hole. The similarity of humans'
      and chimpanzees' behavior on these tasks highlights methodological and conceptual
      problems in studies of chimpanzees' folk physics and suggests alternative
      explanations for their behavior.

PMID- 15971493
TI  - The fine-grained spatial abilities of three seed-caching corvids.
AB  - We used a psychophysical method to examine the ability of three corvid species to
      discern fine-grained spatial information. Nutcrackers, pinyon jays, and scrub
      jays were required to discriminate the distance between two landmarks on a
      computer screen in an operant chamber. All three species were able to
      discriminate between arrays that differed by 20 mm; the discrimination gradients
      for scrub-jays and pinyon jays were sharper than those for nutcrackers, however.
      The results suggest that differences in spatial memory among these species are
      not related to differences in fine-grained perception.

PMID- 15971495
TI  - Spatial configuration and list learning of proximally cued arms by rats in the
      enclosed four-arm radial maze.
AB  - In an enclosed four-arm radial maze, after sampling three experimenter-selected
      baited arms (the study segment) and following rotation of the maze, rats had to
      find the fourth baited arm among all four unblocked arms (test segment). The rats
      learned this task with two sets of arm cues, objects at arms' entrances and full
      arm inserts, each maintained in a fixed configuration. When we changed the
      configuration of one set of arms to its mirror image and that of the other set to
      a more mixed variation by switching opposite and adjacent cued arms, the rats'
      accuracy was similarly disrupted (Experiment 1). In Experiment 2, the same rats
      rapidly recovered their high search accuracy on four new configurations
      recombined from pairs of adjacent arms and pairs of opposite cued arms from t he
      previous finaltwo configurations. Their test segment search accuracy, however,
      was again disrupted when these configurations were varied either only over
      trials' study segments or only over trials' test segments. In Experiment 3,
      however, these rats attained accuracy as high on two sets of cued arms with
      constantly changing configurations as on two sets with constant configurations.
      Thus, the rats were able to separately represent four different spatially stable
      configurations, and then they could learn to represent two of these
      configurations as lists of spatially irrelevant items. We discuss these findings
      in terms of association theory and parallel map theory (Jacobs & Schenk, 2003).

PMID- 15971494
TI  - Two-item same-different concept learning in pigeons.
AB  - We report the first successful demonstration of a simultaneous, two-item same
      different (S/D) discrimination by 6 pigeons, in which nonpictorial color and
      shape stimuli were used. This study was conducted because the majority of
      recently successful demonstrations of S/D discrimination in pigeons have employed
      displays with more than two items. Two pairs of stimulus items were
      simultaneously presented on a touch screen equipped computer monitor. Pigeons
      were reinforced for consistently pecking at either the same (i.e., identical) or
      the different (i.e., nonidentical) pair of items. These pairs were created from
      combinations of simple colored shapes drawn from a pool of six colors and six
      shapes. After acquiring the discrimination with item pairs that differed
      redundantly in both the shape and the color dimensions, the pigeons were tested
      for transfer to items that varied in only one of these dimensions. Although both
      dimensions contributed to the discrimination, greater control was exhibited by
      the color dimension. Most important, the discrimination transferred in tests with
      novel colored, shaped, and sized items, suggesting that the mechanisms involved
      were not stimulus specific but were more generalized in nature. These results
      suggest that the capacity to judge S/D relations is present in pigeons even when
      only two stimuli are used to implement this contrast.

PMID- 15971496
TI  - Effects of identical context on visual pattern recognition by pigeons.
AB  - The effects of identical context on pattern recognition by pigeons for outline
      drawings of faces were investigated by training pigeons to identify (Experiment
      1) and categorize (Experiment 2) these stimuli according to the orientation of
      the mouth-an upright U shape representing a smiling mouth or an inverted U shape
      representing a sad mouth. These target stimuli were presented alone (Pair 1),
      with three dots in a triangular orientation to represent a nose and eyes (Pair
      2), and with the face pattern surrounded by an oval (Pair 3). In Experiment 1,
      the pigeons trained with Pair 1 were most accurate, those trained with Pair 2
      were less so, and those trained with Pair 3 failed to acquire the discrimination
      within eighty 100-trial sessions. The same ordering was found in Experiment 2 for
      pigeons trained on the three pairs simultaneously. The authors suggest that a
      contrasting finding in humans, the face superiority effect, might be due to a
      gain in discriminability resulting from recognition of the pattern as a face. An
      exemplar model of information processing that excludes linguistic coding accounts
      for the present results.

PMID- 15971498
TI  - Testing the scalar expectancy theory (SET) and the learning-to-time model (LeT)
      in a double bisection task.
AB  - Two theories of timing, scalar expectancy theory (SET) and learning-to-time
      (LeT), make substantially different assumptions about what animals learn in
      temporal tasks. In a test of these assumptions, pigeons learned two temporal
      discriminations. On Type 1 trials, they learned to choose a red key after a 1-sec
      signal and a green key after a 4-sec signal; on Type 2 trials, they learned to
      choose a blue key after a 4-sec signal and a yellow key after either an 8-sec
      signal (Group 8) or a 16-sec signal (Group 16). Then, the birds were exposed to
      signals 1 sec, 4 sec, and 16 sec in length and given a choice between novel key
      combinations (red or green vs. blue or yellow). The choice between the green key
      and the blue key was of particular significance because both keys were associated
      with the same 4-sec signal. Whereas SET predicted no effect of the test signal
      duration on choice, LeT predicted that preference for green would increase
      monotonically with the length of the signal but would do so faster for Group 8
      than for Group 16. The results were consistent with LeT, but not with SET.

PMID- 15971497
TI  - A behavior systems view of the organization of multiple responses during a
      partially or continuously reinforced interfood clock.
AB  - We examined how a 50% Pavlovian partial reinforcement (PRF) schedule, versus a
      100% continuous reinforcement (CRF) schedule, altered the asymptotic amount and
      distribution of focal and general search behavior in rats during 48-sec trials
      with and without a four-segment interfood clock (S1-S2-S3-S4-US). Under CRF, but
      not PRF, average asymptotic focal search (nosing in the feeder) increased across
      the last two clock segments (S3 and S4), and more for the clock group than the no
      clock group. Locomotor general search peaked in the second clock segment (S2) for
      the CRF-clock and CRF-no-clock groups and in S3 for the PRF-clock groups.
      Furthermore, the ratio of general search to maximum focal search was higher for
      the PRF-clock group than for the CRF-clock group. This pattern of results
      supports the view that predictable reward presentations temporally organize
      search states and related responses between food presentations. The relative
      expression of these responses varies with the predictability and proximity of
      reward and is more sharply defined in the presence of a clock.

PMID- 15971499
TI  - Socioeconomic factors in EU-funded studies of children's environmental health.
AB  - We performed a survey on socioeconomic factors in 27 studies of children's
      environmental health funded by EU FP4 and FP5. Parental education was the most
      common measure (74%). Socioeconomic factors were predominantly considered as
      confounder (74%) and less often as effect modifier (33%) or independent variable
      (37%). The awareness of the need to study the impact of socioeconomic factors
      further seems to have increased in recent years.

PMID- 15971500
TI  - Effect of sampling frames on response rates in the WHO MONICA risk factor
      surveys.
AB  - Sample surveys are used to investigate occurrence and determinants of diseases in
      populations. Their reliability is influenced by quality of sampling frame and
      response rate. We investigated relationship between sampling frame type and
      response rates and assessed their impact on non-response bias, using data from
      the WHO MONICA Project, where 37 centres in 20 countries conducted sample
      surveys, employing the best locally available sampling frame. Sampling frames
      fell into three categories: Population registers (PR), electoral registers (ER),
      and health care registers (HR). Response rate (rrs) was factored into components
      reflecting quality of sampling frame (contact rate cr) and characterizing
      willingness of sample members to participate (enrolment rate er). The mean
      quality score for the sampling frames was 92% for PR, 87% for HR and 85% for ER;
      they contributed on average 23, 20, and 26% to the respective non-response rates.
      For all frame types and both sexes the lowest quality score occurred in the age
      group 35 - 44, suggesting a reduced ability to track migration of a highly mobile
      population group. The patterns in the age/sex distribution of er indicate at
      least for males in PR and females in HR a potential for non-response bias.
      Estimation of non-response bias through an abbreviated questionnaire failed
      because of low item response. We found that contact rate characterizes sampling
      frame quality. For all frame types it had a major influence on response rate. It
      is likely that low er and low cr cause different kind of bias, requiring
      different measures to minimize their effects.

PMID- 15971501
TI  - The ischemic electrocardiogram: a harbinger for ischemic heart disease
      independent of the blood pressure level. The Copenhagen City Heart Study.
AB  - Information is limited on the co-existence and prognostic association of the
      ischemic electrocardiogram (ECG) and blood pressure. Prospectively collected data
      sets from 28,118 examinations in the Copenhagen City Heart Study were analyzed
      for cardiac morbidity and mortality for a 5.9-year follow-up. The prognosis of
      the ECG, independently of blood pressure, was examined. The Cox proportional
      hazard model was employed to evaluate the prognostic implications of ECG findings
      and relative risk was adjusted for age and multivariately adjusted for
      traditional cardiovascular risk factors. End-points were (1) fatal and non-fatal
      ischemic heart disease (IHD) events and (2) cardiovascular disease (CVD)
      mortality. During a total follow-up period of 166,471 person years (mean: 5.9
      years) 1.481 IHD events were recorded and 1.051 CVD deaths. The relative risk of
      an ischemic ECG was independent of the blood pressure level. The multivariately
      adjusted relative risk for fatal and non-fatal IHD for the ischemic ECG was 1.70
      (95% CI: 1.39-2.09, p < 0.001) in women, and 1.96 (95% CI: 1.67-2.30, p < 0.001)
      in men, and for CVD mortality 1.71 (95% CI: 1.34-2.17, p < 0.001) in women and
      2.08 (95% CI: 1.74-2.49, p < 0.001) in men. An ECG with left ventricular
      hypertrophy (LVH) and ST-depression was the finding with the highest risk for
      future events. LVH by ECG voltage-only was associated with no statistically
      increased risk, except for men treated for arterial hypertension.

PMID- 15971502
TI  - Association of serum caffeine concentrations with blood lipids in caffeine-drug
      users and nonusers - results of German National Health Surveys from 1984 to 1999.
AB  - Previous studies regarding effects of caffeine on lipids focused mainly on coffee
      consumption, the real association of serum caffeine concentrations with blood
      lipids is unclear. 814 caffeine-drug users who had taken any caffeine/caffeine
      containing pharmaceutical products and 623 nonusers without any drug use in the
      last seven days before the medical interview were identified from German National
      Health Surveys from 1984 to 1999. Serum caffeine concentrations were measured by
      using EIA for caffeine-drug users and nonusers in the same laboratory. Blood
      lipids were measured routinely for all survey participants. The association of
      caffeine concentrations with blood lipids was established by means of partial
      correlation analysis and regression analysis. After controlling for influence
      factors, caffeine concentrations were closely positively related to triglycerides
      in caffeine-drug users (male: r = 0.245, p < 0.001; female: r = 0.117, p = 0.018)
      and related to HDL-C in female nonusers (r = 0.245, p < 0.001). No associations
      were found between caffeine concentrations and total cholesterol and LDL-C levels
      in any groups of our study. Acute intake of caffeine might increase triglycerides
      levels especially in men while chronic intake of caffeine might be weakly but
      positively associated with HDL-C concentrations in women. The effects of caffeine
      on the pathogenesis of cardiovascular diseases should be further confirmed
      through epidemiological studies.

PMID- 15971503
TI  - A community-based follow-up study on diabetic retinopathy among type 2 diabetics
      in Kinmen.
AB  - The purpose of this follow-up study was conducted to assess the incidence and
      risk factors of diabetic retinopathy (DR) among type 2 diabetics in Kinmen,
      Taiwan. A penal of eye screening regimes were performed yearly for 971 type 2
      diabetics by two senior ophthalmologists using indirect ophthalmoscopy and 45
      degree color fundus photography to examine fundus after dilating pupils from 1999
      to 2002. 74.7% (725/971) of diabetics had been screened at least two times during
      this period. Among the 548 type 2 diabetics who had no DR at first screening, 93
      subjects developed any type of DR. The 3-year 18.2% cumulative incidence was (95%
      CI: 14.8-21.5%) and incidence density was 6.62% per year (95% CI: 5.36-8.06% per
      year). Using Cox regression model, HbAlc revealed the significantly dose response
      relationship to the development of DR (chi2-test for trend = 9.41, p < 0.05)
      after controlling for confounding factors. Other independent predictors related
      to the development of DR included duration of diabetes (RR: 1.09, 95% CI: 1.05
      1.13), higher systolic blood pressure (>140 vs. < 140 mm Hg, RR: 1.96, 95% CI:
      1.23-3.12), and higher triglyceride (> 200 vs. < 200 mg/dl, RR: 1.60, 95% CI:
      1.01-2.54). In conclusion, in addition to poor glycemic control of which is the
      most significant risk factor for the development of DR, longer duration of
      diabetes, higher systolic blood pressure, and elevated serum triglyceride levels
      were also associated with the development of DR among type 2 diabetics in Kinmen.

PMID- 15971504
TI  - Increasing trend of childhood type 1 diabetes in Franche-Comte (France): analysis
      of age and period effects from 1980 to 1998.
AB  - AIMS/HYPOTHESIS: A study was conducted by the Franche-Comte Regional Association
      of Private Practitioners (Union Regionale des Medecins Liberaux de Franche-Comte)
      to assess trends in childhood-onset Type 1 diabetes in this administrative region
      of France, between 1980 and 1998. METHODS: Cases of childhood-onset Type 1
      diabetes (aged 0-14 years) were retrospectively recorded with the help of general
      practitioners, private specialists and hospitals in the Franche-Comte and
      surrounding administrative regions. Incidence rates and trends during the period
      were analysed using Poisson regression. RESULTS: During the 19-year study period,
      308 cases of childhood-onset Type 1 diabetes were identified. The level of case
      ascertainment was estimated to be 80.6% (95% CI: 74.7, 87.4). The male-to-female
      sex ratio was 1.03. The World standardised incidence rate was 6.90/100,000. The
      incidence rate was 6.03 (95% CI: 4.76, 7.53) for children aged 0 to 4 years, 6.45
      (95% CI: 5.23, 7.88) for children aged 5-9 years and 8.56 (95% CI: 7.18, 10.13)
      for those aged 10-14 years. The annual increase rate was 4.9%, continuous and
      regular, without any deviation. This trend did not differ according to gender or
      age group. CONCLUSION/INTERPRETATION: These results confirm that the incidence
      and the increase rate in childhood Type 1 diabetes in France are average compared
      to in other European countries over an extended period of time. Furthermore, the
      regular and linear increase in incidence supports the hypothesis of causal
      environmental factors diffusing over time. The complementary data provided also
      illustrate the role that private practitioners may play by their implication in
      epidemiology and public health.

PMID- 15971505
TI  - Smoking as a determinant for plasma levels of testosterone, androstenedione, and
      DHEAs in postmenopausal women.
AB  - The aim of the present study was to investigate whether current smoking, ex
      smoking, or amount of current smoking among postmenopausal women was associated
      with plasma levels of testosterone, and rostenedione, and DHEAs. About 65,000
      women in Sweden have participated in two population-based prospective cohort
      studies where blood samples were collected at baseline, and information on life
      style, reproductive history and anthropometrical measurements were available. The
      present study was based on 407 control subjects from a previous nested case
      control study on the relation between steroid hormone levels and risk of breast
      cancer. A multivariate logistic regression analysis, adjusted for potential
      confounders, was used in order to obtain odds ratios (OR) with 95% confidence
      intervals. There was a high risk of high testosterone levels (above the median)
      in current vs. never smokers, OR: 1.85 (1.06-3.23). Risk of high testosterone
      levels increased by amount of daily smoking (increments of 10 cigarettes/day),
      OR: 1.55 (1.02-2.37). Ex-smoking was associated with high testosterone levels,
      OR: 1.56 (0.98-2.47). Current smoking and increasing amount of current smoking
      were weakly associated with high androstenedione levels. However, these
      associations did not reach statistical significance. No association was seen
      between smoking habits and DHEAs levels. We conclude that current smoking, and
      increasing amount of daily smoking, is associated with high testosterone levels.

PMID- 15971506
TI  - Modelling the progression towards duodenal cancer among patients with familial
      polyposis on the basis of two different score profiles.
AB  - The objective was to design a method that considers, on clinical arguments, the
      likely existence of patient subgroups with different evolution profiles. The
      method is applied in familial adenomatous polyposis to predict the proportion of
      patients that would develop duodenal cancer. A subject-specific linear mixed
      effects model was elaborated to explicitly model heterogeneity in regression
      parameters. The estimates of the parameters were obtained by Bayesian inference
      using Gibbs sampling. The application concerned two potential polyposis
      subgroups: stable-state and progressive. Each patient's score was expressed in
      function of his putative subgroup, the reference subgroup mean score (intercept),
      the rate of change (slope), and time. The estimated proportion of stable-state
      patients was 35%. In progressive-state patients, the estimated annual score
      increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the
      proportion of patients with a score > or = 9 is near 43% at age 60 (36-50%) and
      50% at 70 (43-57%). The method indicates the evolution profile of each subject,
      which facilitates therapeutic decisions. The modelling may be extended to other
      more complex situations with several subgroups, with different change rates, or
      with various genetic or therapeutic profiles.

PMID- 15971507
TI  - The epidemiology of anophthalmia and microphthalmia in Sweden.
AB  - Infants with a clinical diagnosis of anophthalmia or microphthalmia were
      identified from four health registers in Sweden, covering different parts of the
      period 1965-2001. During the observation period, the rate of anophthalmia
      decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered
      rate of microphthalmia increased markedly during the observation period to reach
      a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified
      children had a chromosome anomaly. There was no geographical variation in
      prevalence and infants born in urban or rural districts had, if anything, a lower
      risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non
      eye malformations were more common at anophthalmia (63%) than at microphthalmia
      (30%). Sex ratio was normal and no statistically significant variation between
      sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye
      malformations) could be demonstrated. There was a marked risk increase with
      maternal age but no certain parity effect, no effect of maternal education, but a
      possible association with subfertility. Maternal smoking in early pregnancy
      seemed to increase the risk for anophthalmia or microphthalmia in the absence of
      a coloboma.

PMID- 15971508
TI  - Air pollution and respiratory drug use in the city of Como, Italy.
AB  - STUDY OBJECTIVE AND SETTING: Particulate air pollution has a known negative
      effect on human respiratory health, often studied with hospital admissions,
      emergency room access, or mortality as health indicators. We evaluate respiratory
      drug dispensing data as health indicators for the effects of total suspended
      particles (TSP) air pollution in the city of Como (84,713 inhabitants). DESIGN:
      Weekly count of individual patients with respiratory drug dispensed (Cases) and
      weekly dispensed daily defined doses (DDD) of drugs were modelled with weekly air
      mean concentrations of TSP using a Poisson regression model adjusted for long
      term trends, seasonal variations, calendar variations due to holidays, and
      weather. MAIN RESULT: Relative risks (RR) were expressed for a variation from
      10th to 90th percentile of TSP (29-92 microg/m3). Weekly aggregation was used in
      consideration of the complexity of drug dispensing data and potential biases of
      daily aggregation. For weekly mean concentrations of TSP, RR = 1.082 (95%
      Confidence level (CI) 1.002-1.169) for Cases and RR = 1.137 (95% CI 1.044-1.238)
      for DDD. CONCLUSION: Our study concludes that both Cases and DDD of dispensed
      respiratory drugs could be useful for epidemiological surveillance of air
      pollutant health effects. Further investigation may routinely allow health and
      economics considerations, producing a stimulating new tool for health policy
      makers.

PMID- 15971511
TI  - Cross border HIV epidemic among injecting drug users of Himalayan West Bengal.

PMID- 15971509
TI  - Daily tea drinking is associated with a low level of depressive symptoms in the
      Finnish general population.
AB  - Tea drinking has been suggested to be beneficial in neurodegenerative diseases
      where depressive mood is a common symptom. Nevertheless, it is not known whether
      there are any associations between tea drinking and depression in general
      populations. In this study we investigated these associations in a sample of the
      Finnish general population (n = 2011) using a postal questionnaire and the Beck
      Depression Inventory (BDI). Those who reported drinking tea daily were less
      depressed than the others. They had a lower mean BDI score and also a lower
      prevalence of depression. None of those whose daily tea intake was five cups or
      more had depression. Several potential confounding factors were included in the
      final sex- and age-adjusted multivariate logistic regression model which
      suggested that those who drink tea daily may have a significantly reduced risk of
      being depressed (adjusted odds ratio 0.47, 95% confidence interval 0.27-0.83). In
      conclusion, an inverse relationship between daily tea drinking and the risk of
      being depressed was found in a relatively large general population sample.
      Nevertheless, the underlying mechanisms are unresolved and further studies are
      needed.

PMID- 15971510
TI  - A study of excess mortality during influenza epidemics in the Czech Republic,
      1982-2000.
AB  - Influenza related mortality rates have been established in many countries;
      nevertheless, studies focusing on the Central European population have been rare
      to date. We assess mortality attributable to influenza by comparing all cause
      mortality and mortality due to diseases of the circulatory system during
      influenza epidemic and non-epidemic periods, as defined by acute respiratory
      infection surveillance data. Data on total mortality, mortality due to diseases
      of the circulatory system and surveillance data for influenza and other
      respiratory infections were used in a general linear model with a logarithmic
      link for dependence of left censored mortality data over time, and week as a
      categorical factor. Results of the analysis show statistically significant (p
      <0.001) differences in excess mortality rates between influenza epidemic and non
      epidemic periods in the Czech Republic between 1982 and 2000. We estimate that
      2.17% of all cause mortality, and 2.57% of mortality due to diseases of the
      circulatory system throughout the study period was attributable to influenza,
      with an estimated annual average of 2661 and 1752 deaths respectively. The
      highest numbers of deaths were reported during seasons when influenza A/H3N2 was
      the predominant circulating strain. Improving vaccination coverage against
      influenza is considered to be the primary strategy for prevention of influenza
      associated mortality.

PMID- 15971512
TI  - Early sexual intercourse.
AB  - OBJECTIVES: This analysis estimates the percentage of adolescents who have had
      sexual intercourse by age 14 or 15 and examines characteristics at age 12 or 13
      that are associated with early sexual activity. DATA SOURCE: The data are from
      the 1996/97, 1998/99 and 2000/01 National Longitudinal Survey of Children and
      Youth, conducted by Statistics Canada. ANALYTICAL TECHNIQUES: Descriptive
      statistics were used to determine the proportion of 14- or 15-year-olds who have
      had sexual intercourse. Logistic regression was used to model sexual activity at
      age 14 or 15 in relation to the adolescent's characteristics at age 12 or 13.
      MAIN RESULTS: The percentages of boys and girls who had had intercourse by age 14
      or 15 were almost the same--12% and 13%--but the characteristics associated with
      such behaviour differed. Among girls, region of residence, the onset of puberty,
      weak self-concept, having tried smoking or drinking, and not being overweight
      were significantly associated with early sexual activity. For boys, older age, a
      poor relationship with parents, low household income, and having tried smoking
      were significant.

PMID- 15971513
TI  - The journey to quitting smoking.
AB  - OBJECTIVES: This article outlines smoking trends over the past 10 years among the
      population aged 18 or older. Factors associated with smoking cessation and
      relapse are examined, as well as factors associated with having no intention of
      quitting in the next 6 months. DATA SOURCES: Data are from the household cross
      sectional and longitudinal components of Statistics Canada's National Population
      Health Survey (1994/95 to 2002/03) (NPHS) and from the 2000/01 and 2003 Canadian
      Community Health Survey (CCHS). ANALYTICAL TECHNIQUES: Trends in smoking rates
      were calculated using cross-sectional data from the NPHS and the CCHS. Factors
      associated with cessation and relapsing were examined using pooling of repeated
      observations over two-year periods and logistic regression based on NPHS
      longitudinal data from 1994/95 to 2002/03. Factors associated with having no
      plans to quit were examined with logistic regression, based on 2003 CCHS cross
      sectional data. MAIN RESULTS: In 2003, 19% of the Canadian population aged 18 or
      older smoked cigarettes daily, down 7 percentage points from a decade earlier.
      Smoking cessation, relapsing and having no plans to quit were all associated with
      addiction levels, notably, cigarettes smoked per day. Smoke-free homes and
      workplace smoking bans were associated with reduced cigarette consumption.